PMID- 29632622
TI  - Negative and positive control ranges in the bacterial reverse mutation test:
      JEMS/BMS collaborative study.
AB  - A large-scale study was conducted by multiple laboratories affiliated with the
      Japanese Environmental Mutagen Society and the Bacterial Mutagenicity Study Group
      to investigate possible proficiency indicators for the bacterial reverse mutation
      test with a preincubation procedure. Approximately 30 laboratories generated
      negative and positive control count data and dose-response curves of the positive
      control articles for the bacterial reverse mutation test, with assays conducted
      annually from 2013 to 2016. Overall, the majority of the negative and positive
      control counts for Salmonella Typhimurium strains TA100, TA1535, TA98, and
      TA1537, and Escherichia coli strain WP2uvrA, with and without S9 mix, were within
      the range of the means +/-2* standard deviation. The negative counts were
      normally distributed (strains TA100, TA98, and WP2uvrA) or followed Poisson
      distribution (strains TA1535 and TA1537), and the positive control counts for all
      strains were approximately normally distributed. In addition, the distribution of
      the negative and positive control counts was relatively constant over the 4
      years. The number of revertant colonies increased in a dose-dependent linear or
      exponential fashion up to the recommended doses for the respective positive
      control articles in Japan. These data are valuable for determining the acceptance
      criteria and an estimation of the laboratory proficiency for the bacterial
      reverse mutation test.

PMID- 29632623
TI  - ?

PMID- 29632624
TI  - ?
AB  - We here report the case of a 58-year old female patient with no particular past
      medical history, presenting with a 5-year history of vulvar pruritis, drought and
      vulvodynia at the Department of Dermatology. Clinical examination showed diffuse
      porcelaine lesions at the level of the vulva, with a yellowish hemispheric
      nodular lesion measuring 1 cm in diameter on the whitish plates and some
      excoriated lesions due to scratching. A skin biopsy was performed at the level of
      the whitish lesions and at the level of the nodular lesion. Histological
      examination suggested epidermoid carcinoma for the budding lesion and atrophic
      vulvar lichen sclerosus for the porcelaine lesions. Surgical treatment was
      recommended associated with radiation therapy. This study aims to highlight the
      risk for atrophic vulvar lichen sclerosu degeneration.

PMID- 29632625
TI  - ?
AB  - We here report the case of a16-year old patient, with no particular past medical
      history, presenting, with skin swelling at the level of the forefoot evolving for
      02 years, at the Department of Dermatology. Clinical examination showed hard
      budding cutaneous mass painless on palpation covering the 2nd, the 3rd and the
      4th, right toes, measuring 4 cm in large diameter. The remainder of the clinical
      examination was normal, without adenopathies. Skin biopsy was performed at the
      level of the tumor and histological examination showed carcinoma in situ.
      Surgical treatment was recommended. Bowen's disease is a relatively rare squamous
      intraepithelial carcinoma in situ. It mainly affects adults at any age, with
      predominance in women. The diagnosis is suspected on the basis of clinical
      examination, but it is confirmed by the anatomo-pathological examination.

PMID- 29632626
TI  - ?
AB  - Giant urinary bladder stone is defined as a stone with a weight higher than 100
      g. It is rare in women, accounting for approximately 2%. Its occurrence in the
      urinary bladder does not exceed 5% of the whole of the urinary tract. In women,
      the occurrence of urinary bladder stone is often secondary to a predisposing
      factor including intravesical foreign body, neurogenic bladder, repeated urinary
      infections, a history of surgery treating stress urinary incontinence. Therefore,
      there are some patients with a bladder stones without any obvious cause, such as
      primary idiopathic stone. We here report the case of a 31-year old patient with
      giant urinary bladder stone affecting the superior part of the urinary tract
      causing acute renal failure. The patient initially underwent bilateral
      nephrostomies to drain the superior part of the urinary tract; then giant urinary
      bladder stone was removed by open cystolithotomy. Etiological assessment didn't
      show any obvious cause.

PMID- 29632627
TI  - ?
AB  - Necrobiosis lipoidica is a rare granulomatous dermatosis. It occurs in 0.3-1.2%
      of diabetic patients mainly at the level of the leg. The lesions appear as
      erythematous plaques with central depressions. We here report the case of a 21
      year old female patient with a 6-year history of type 1 diabetes presenting with
      a 1-year history of well circumscribed, symmetrical and asymptomatic erythematous
      plaques with atrophic yellowish center at the level of the anterior compartments
      of the legs (A, B). The diagnosis of necrobiosis lipoidica was suspected, a
      biopsy was performed which confirmed the diagnosis. The patient had a
      granulomatous inflammatory reaction with palisade-like border disposed around
      poorly delimited foci of altered connective tissue on the entire dermis layer.
      The inflammatory reaction was also characterized by multinucleate giant cells,
      dendrocytes and lipid deposits. Local corticosteroid therapy was prescribed.
      Patient's evolution was marked by the persistence of the lesions.

PMID- 29632628
TI  - ?
AB  - This study aimed to describe the practice of electroconvulsivotherapy (ECT) at
      the University Hospital of Monastir (Tunisia). We conducted a retrospective study
      of all patients treated by ECT at the University Hospital of Monastir between
      2002 and 2013. 80 patients were enrolled in the study (60 men and 20 women, with
      an average age of 42.1+/-15.7 years), accounting for 1.4% of all patients
      hospitalized in Psychiatry Department during the study period. The total number
      of ECT sessions was 784. In 50% of patients, the primary diagnosis was a major
      isolated or recurring depressive disorder. The majority of patients (78.8%) had
      undergone only one ECT session, with an average number of sessions of 8.1 +/-
      4.9. The most used anesthetic product was the propofol (97.4%). In 71% of cases
      the energy delivered was between 40 and 80 joules and it was positively
      correlated with patients' age. The average duration of the motor seizure was 22.3
      +/- 7.2 seconds and it was negatively correlated with patients' age. The highest
      response rate was found in depression scores (64.3%). Immediate adverse effects
      occurred in 51.2% of patients. Finally, 20% of patients continued to undergo
      maintenance ECT sessions on a weekly or a biweekly basis. The practice of ECT at
      the University Hospital of Monastir has been little developed in terms of number
      of patients and ECT sessions. Efforts should be made to promote the use of this
      method.

PMID- 29632629
TI  - [Peripartum cardiomyopathy].
AB  - Peripartum cardiomyopathy (PP-CMP) or Meadows' syndrom, is a dilated
      cardiomyopathy which occurs during or following pregnancy. It is characterized by
      heart failure with a systolic left ventricle ejection fraction of less than 45%.
      It is rare and its pathophysiologic mechanism is poorly elucidated. From a
      clinical point of view, it is characterized by unespected heart failure with
      rapid onset of symptoms, unpredictable evolution and risk of refractory
      cardiogenic shock, justifying patient's management in Cardiovascular Unit. PP-CMP
      requires no specific treatment compared to other causes of heart failure. We here
      report the case of a 29-year old primip at 32 weeks of amenorrhea presenting with
      congestive heart failure associated with peripartum cardiomyopathy. The aim of
      this study was to highlight the features of this heart disease which, despite its
      rarity, should not be disregarded by obstetricians.

PMID- 29632630
TI  - The physician-scientists: rare species in Africa.
AB  - There is paucity of physician-scientists in Africa, resulting in overt dependence
      of clinical practice on research findings from advanced "first world" countries.
      Physician-scientists include individuals with a medical degree alone or combined
      with other advanced degrees (e.g. MD/MBChB and PhD) with a career path in
      biomedical/ translational and patient-oriented/evaluative science research. The
      paucity of clinically trained research scientists in Africa could result in dire
      consequences as exemplified in the recent Ebola virus epidemic in West Africa,
      where shortage of skilled clinical scientists, played a major role in disease
      progression and mortality. Here we contextualise the role of physician-scientist
      in health care management, highlight factors limiting the training of physician
      scientist in Africa and proffer implementable recommendations to address these
      factors.

PMID- 29632631
TI  - About a subcutaneous calcification.

PMID- 29632632
TI  - Man with a swollen mass on sacrococcygeal region.

PMID- 29632633
TI  - ?

PMID- 29632634
TI  - Outcome after neoadjuvant chemotherapy in elderly breast cancer patients - a
      pooled analysis of individual patient data from eight prospectively randomized
      controlled trials.
AB  - Introduction: Recent studies showed the high and independent impact of age (<40
      years) on pathologic complete response (pCR) and prognosis for patients
      undergoing neoadjuvant chemotherapy (NACT). Some physicians might not consider
      elderly patients (>65 years) for NACT due to poor prognosis or higher toxicity.
      The aim of this analysis is to help selecting appropriately elderly women who
      would benefit from NACT. Secondly, survival parameters are investigated in
      several histological subgroups. Methods: From 1998 to 2010, eight prospectively
      randomized German Breast Group (GBG) trials of anthracycline- and taxane-based
      NACT were performed and analyzed in this study. Results: Compared to the overall
      average, elderly women had significant larger tumors and more overall lymph node
      involvement. Histologically, they had more G2 tumors, more estrogen-receptor
      positive tumors. pCR (ypT0 ypN0) was strongly associated with age. The
      multivariable logistic regression analysis of clinical parameters showed that
      young age, clinical stage T4, invasive ductal cancer and poor differentiated
      breast cancer are predictive for high pCR. The multivariate analyses of molecular
      subgroups showed that age >65years is a predictor of significant lower pCR in
      HER2- breast cancers. Nonetheless, HER2+ patients showed pCR rates as high- and
      HR+/HER2+ even higher - pCR rates compared to younger patients. Discussion: This
      study underlines the unfavorable impact of higher age on pCR, but it shows a
      realistic chance for pCR if NACT is applied - especially for HER2+ patients.
      Furthermore, elderly patients with non-TNBC showed a good prognosis (comparable
      to younger patients) regarding overall survival, even if they do not have pCR.

PMID- 29632635
TI  - Verification of the methodology for evaluating tumor-infiltrating lymphocytes in
      colorectal cancer.
AB  - Background: The density of tumor-infiltrating lymphocytes (TILs) have been
      reported to reflect antitumor immune response and correlate with prognosis in
      malignancy. However, the methodology for evaluating the density of TILs by an
      immunohistochemical analysis differs among reports. The aim of this study was to
      verify the methodology for evaluating the density of TILs by immunohistochemical
      analysis and thereby identify the optimum methodology in clinical setting.
      Methods: Three-hundred-thirteen patients who underwent curative operation for
      stage II/III colorectal cancer were enrolled. We retrospectively examined the
      density of TILs using immunohistochemical staining according to each method as
      follows: 1) subset of lymphocytes (i.e. CD4+/CD8+), 2) selected fields (i.e. at
      random or focusing on hot spots), 3) location in low-power field (i.e. the
      invasive margin [TILsIM] or the center of the tumor [TILsCT] or the surface of
      the tumor [TILsST]), and 4) location in high-power field (i.e. in tumor stroma
      [sTILs] or intra-tumor cells [iTILs] or total TILs [tTILs: sTILs+iTILs]). We then
      assessed the prognostic value of the density of TILsIM evaluated as described
      above. We also evaluated the correlation between the density of TILsIM and that
      of TILsCT/TILsST. Results: Only the densities of CD8+sTILsIM and CD8+tTILsIM
      evaluated in randomly selected fields were significantly associated with the
      survival. Furthermore, the density of CD8+TILsIM was significantly associated
      with that of CD8+TILsCT and CD8+TILsST. Conclusions: We concluded that best and
      easiest way to evaluate the density of TILs in the clinical setting may be to
      assess the density of CD8+tTILsIM in randomly selected fields.

PMID- 29632636
TI  - miR-145 expression enhances integrin expression in SK-GT-4 cell line by down
      regulating c-Myc expression.
AB  - Adenocarcinoma of the esophagus is increasing in frequency and is the 6th most
      common cause of cancer death in North America. In adenocarcinoma cell lines, we
      have previously demonstrated that expression of miR-145, leads to enhanced
      invasion, resistance to anoikis and better attachment to fibronectin in
      esophageal adenocarcinoma. In contrast, expression of miR-145 acts as a tumor
      suppressor in squamous cell carcinoma. The molecular mechanisms responsible for
      the oncogenic effects of miR-145 were investigated. In this report, we
      demonstrate that we can partially recreate the miR-145 effects in EAC by knock
      down of the expression of c-Myc, which is one of the targets of miR-145. Knocking
      down of c-Myc expression resulted in upregulation of integrin subunits alpha5 and
      beta3. Finally, we demonstrated that integrin alpha5 expression correlates to
      fibronectin attachment potential whereas integrin beta3 expression correlates
      with resistance to anoikis and invasion potential. Finally, we demonstrate that
      expression of miR-145 in esophageal adenocarcinoma cell line (SK-GT-4) enhances
      tumor growth and metastasis in a NOD/SCID xenograft model. Overall, the oncogenic
      potential of miR-145 in EAC appears to be mediated by downregulation of c-Myc
      leading to the expression of integrins subunits alpha5 and beta3.

PMID- 29632637
TI  - RPN2 is effective biomarker to predict the outcome of combined chemotherapy
      docetaxel and cisplatin for advanced gastric cancer.
AB  - Preoperative chemotherapy, often using docetaxel and cisplatin, is a famous
      treatment option for advanced gastric cancer in Japan. But, there are no
      effective biomarkers that predict the therapeutic outcome on gastric cancer.
      Ribophorin II (RPN2) silencing, which decreases glycosylation of P-glycoprotein
      (P-gp) and membrane localization, restores the sensitivity to docetaxel and
      cisplatin. We inquired whether RPN2 expression in advanced gastric cancer biopsy
      tissues may be a predictive biomarker for docetaxel and cisplatin combination
      preoperative chemotherapy. We judged RPN2 expression immunohistochemically in
      upper endoscopic biopsy tissues from 40 advanced gastric cancer patients, who
      received the combination preoperative chemotherapy of docetaxel and cisplatin and
      gastrectomy with D2 resection during 2008-2014, and compared clinicopathological
      effects between RPN2-positive and RPN2-negative groups. We also examined
      sensitivity of RPN2-knockout gastric cancer cells by genome editing to docetaxel
      and cisplatin. RPN2 expression was observed in 19 of 40 gastric cancer cases. The
      RPN2-negative group had better clinicopathological responses to docetaxel and
      cisplatin combination chemotherapy than the RPN2-positive group, especially, in
      assessment of the histopathological criteria to preoperative chemotherapy. And
      RPN2-negative group had a significantly higher overall survival and progression
      free survival compared to the RPN2-positive group. We also found RPN2-knockout to
      change docetaxel and cisplatin sensitivity in vitro. RPN2 expression in upper
      endoscopic biopsy tissues can be an effective predictive biomarker for the
      treatment outcome to docetaxel and cisplatin combination preoperative
      chemotherapy in advanced gastric cancer.

PMID- 29632638
TI  - Early hypertension is associated with better clinical outcomes in gastric cancer
      patients treated with ramucirumab plus paclitaxel.
AB  - Anti-vascular endothelial growth factor (VEGF) therapeutics such as bevacizumab,
      which are widely used in cancer treatment, commonly leads to hypertension.
      Moreover, bevacizumab-induced hypertension is associated with improved clinical
      outcomes in several cancers. We retrospectively analyzed 89 patients with
      histologically confirmed advanced gastric cancer who received the human
      monoclonal anti-VEGF receptor-2 antibody ramucirumab plus paclitaxel at our
      hospital between June 2015 and October 2016 to evaluate the impact of treatment
      associated hypertension occurring within the first two treatment cycles ("early
      hypertension") on outcome. The objective response rate was 40%, median
      progression-free survival was 5.4 months, and overall survival was 10.4 months,
      which is similar to previous reports. Early hypertension in patients who received
      more than two cycles of ramucirumab + paclitaxel was associated with longer
      progression-free and overall survival. Objective response rates were also higher
      in patients with early hypertension. These data indicate that early hypertension
      may be predictive of better outcomes in gastric cancer patients who receive
      ramucirumab + paclitaxel treatment.

PMID- 29632639
TI  - Reduced expression of alpha-L-Fucosidase-1 (FUCA-1) predicts recurrence and
      shorter cancer specific survival in luminal B LN+ breast cancer patients.
AB  - Background: The lysosomal enzyme alpha-L-Fucosidase-1 (FUCA-1) catalyzes the
      hydrolytic cleavage of terminal fucose residues. FUCA-1 gene is down-regulated in
      highly aggressive and metastatic human tumors as its inactivation perturbs the
      fucosylation of proteins involved in cell adhesion, migration and metastases.
      Results: Negativity to FUCA-1 was significantly related to the development of
      later recurrences in breast cancer patients with lymph node involvement at
      diagnosis. Cancer specific survival of luminal B LN+ patients was influenced by
      FUCA-1 expression as luminal B LN+ patients with positive expression had a longer
      cancer specific survival. FUCA-1 mRNA expression was inversely related to cancer
      stage and lymph node involvement. WB and qPCR analysis of FUCA-1 expression in
      breast cancer-derived cell lines confirmed an inverse relationship with tumor
      aggressiveness. Conclusions: This study shows that, within LN+ breast cancer
      patients, FUCA-1 is able to identify a sub-set of non recurrent patients
      characterized by the positive expression of FUCA-1 and that, within luminal B LN+
      patients, the expression of FUCA-1 predicts longer cancer specific survival.
      Methods: We have analyzed FUCA-1 in 305 breast cancer patients by
      Immunohistochemistry (IHC), and by qPCR in breast cancer patients and in breast
      cancer cell lines.

PMID- 29632640
TI  - The Wnt-beta-catenin signaling regulated MRTF-A transcription to activate
      migration-related genes in human breast cancer cells.
AB  - MRTF-A is a transcriptional co-activator being critical for multiple processes
      including tissue fibrosis and cancer metastasis. The Rho-actin signaling
      stimulates the nuclear translocation and transcriptional activity of MRTF-A with
      little effect on the expression of MRTF-A gene. High expression of MRTF-A was
      observed in pancreatic cancer tissues and in TGF-beta treated breast cancer
      cells. However, the mechanism for the upregulation of MRTF-A gene remains
      unclear. In this study, we showed that the transcription of MRTF-A was regulated
      by the Wnt-beta-catenin signaling in breast cancer cells. LiCl treatment, Wnt3a
      treatment or beta-catenin overexpression enhanced the transcription of MRTF-A
      gene. In agreement, depletion of beta-catenin with siRNA diminished MRTF-A
      transcription. With ChIP assays, beta-catenin was identified to interact with the
      MRTF-A promoter whereby it increased histone H4 acetylation and RNA polymerase II
      association. Further, results of RT-qPCR and Western-blotting supported that the
      transcriptional co-activator activity of MRTF-A was controlled by both the Rho
      actin and the Wnt-beta-catenin signaling pathways. MRTF-A was required for cell
      migration stimulated by the Wnt-beta-catenin signaling. Taken together, our
      results suggest that MRTF-A integrates the Rho-actin and the Wnt-beta-catenin
      signaling to regulate migration-related genes and consequently increases the
      mobility of breast cancer cells.

PMID- 29632641
TI  - MEIS-1 level in unresectable hepatocellular carcinoma can predict the post
      treatment outcomes of radiofrequency ablation.
AB  - Radiofrequency ablation (RFA) is a local-ablative therapy for unresectable
      hepatocellular carcinoma (HCC). At present, there is no predictive marker for RFA
      treatment outcomes. This work aimed to valuate myeloid ecotropic viral
      integration site 1 (MEIS-1) in predicting post-RFA treatment outcomes of
      unresectable HCC patients. The time to progression (TTP) and overall survival
      (OS) of 81 HCC patients who received RFA treatment were measured. The protein
      level of MEIS-1 in tumor specimens was measured by western blot. The role of MEIS
      1 in RFA-treating HCC in vivo growth nude mouse model was examined via PET/CT
      imaging. Higher level of MEIS-1 in tumor tissue is associated with better RFA
      treatment outcomes. The median TTP was 9.0 (95% confidence interval [CI]: 6.8
      11.3) months in patients with high MEIS-1 expression (n = 43) versus 6.0 (95% CI:
      4.6-7.4) months in patients with low MEIS-1 expression (n = 38). Moreover, in
      rodent HCC model we found overexpression of MEIS-1 enhanced the anti-tumor effect
      of RFA treatment. We conclude that high level of MEIS-1 expression predicts
      better RFA treatment outcome in HCC.

PMID- 29632642
TI  - PIK3CA and KRAS mutations in cell free circulating DNA are useful markers for
      monitoring ovarian clear cell carcinoma.
AB  - Ovarian clear cell carcinoma (OCCC) exhibits distinct phenotypes, such as
      resistance to chemotherapy, poor prognosis and an association with endometriosis.
      Biomarkers and imaging techniques currently in use are not sufficient for
      reliable diagnosis of this tumor or prediction of therapeutic response. It has
      recently been reported that analysis of somatic mutations in cell-free
      circulating DNA (cfDNA) released from tumor tissues can be useful for tumor
      diagnosis. In the present study, we attempted to detect mutations in PIK3CA and
      KRAS in cfDNA from OCCC patients using droplet digital PCR (ddPCR). Here we show
      that we were able to specifically detect PIK3CA-H1047R and KRAS-G12D in cfDNA
      from OCCC patients and monitor their response to therapy. Furthermore, we found
      that by cleaving wild-type PIK3CA using the CRISPR/Cas9 system, we were able to
      improve the sensitivity of the ddPCR method and detect cfDNA harboring PIK3CA
      H1047R. Our results suggest that detection of mutations in cfDNA by ddPCR would
      be useful for the diagnosis of OCCC, and for predicting its recurrence.

PMID- 29632643
TI  - Analysis of the 9p21.3 sequence associated with coronary artery disease reveals a
      tendency for duplication in a CAD patient.
AB  - Tandem segmental duplications (SDs) greater than 10 kb are widespread in complex
      genomes. They provide material for gene divergence and evolutionary adaptation,
      while formation of specific de novo SDs is a hallmark of cancer and some human
      diseases. Most SDs map to distinct genomic regions termed 'duplication blocks'.
      SDs organization within these blocks is often poorly characterized as they are
      mosaics of ancestral duplicons juxtaposed with younger duplicons arising from
      more recent duplication events. Structural and functional analysis of SDs is
      further hampered as long repetitive DNA structures are underrepresented in
      existing BAC and YAC libraries. We applied Transformation-Associated
      Recombination (TAR) cloning, a versatile technique for large DNA manipulation, to
      selectively isolate the coronary artery disease (CAD) interval sequence within
      the 9p21.3 chromosome locus from a patient with coronary artery disease and
      normal individuals. Four tandem head-to-tail duplicons, each ~50 kb long, were
      recovered in the patient but not in normal individuals. Sequence analysis
      revealed that the repeats varied by 10-15 SNPs between each other and by 82 SNPs
      between the human genome sequence (version hg19). SNPs polymorphism within the
      junctions between repeats allowed two junction types to be distinguished, Type 1
      and Type 2, which were found at a 2:1 ratio. The junction sequences contained an
      Alu element, a sequence previously shown to play a role in duplication. Knowledge
      of structural variation in the CAD interval from more patients could help link
      this locus to cardiovascular diseases susceptibility, and maybe relevant to other
      cases of regional amplification, including cancer.

PMID- 29632644
TI  - Pomalidomide promotes chemosensitization of pancreatic cancer by inhibition of NF
      kappaB.
AB  - Introduction: Nuclear factor kappaB (NF-kappaB) plays an important role in cancer
      progression and causes therapeutic resistance to chemotherapy. Pomalidomide, a
      third-generation immunomodulating drug derived from thalidomide, has been
      approved for uncontrolled multiple myeloma. We hypothesized that pomalidomide may
      inhibit the anticancer agent-induced NF-kappaB activity and enhance
      chemosensitization of combination chemotherapy with gemcitabine and S1 (Gem/S1)
      in pancreatic cancer. Methods: In vitro, we assessed NF-kappaB activity,
      induction of caspase cascade, cell apoptosis and cell proliferation using human
      pancreatic cancer cell lines (MIA PaCa-2 and PANC-1). In vivo, we established an
      orthotopic xenograft mouse model for human pancreatic cancer by injection of PANC
      1 cells. At 5 weeks after injection, the animals were randomly divided into four
      groups and treated with Gem (100 mg/kg) /S1 (10 mg/kg), with oral administration
      of pomalidomide (0.5 mg/kg), with combination of gemcitabine, S1, and
      pomalidomide or vehicle only. Results: Although chemotherapeutic agents induced
      NF-kappaB activation in pancreatic cancer cells, pomalidomide inhibited
      anticancer agent-induced NF-kappaB activation (p < 0.01). Of the four groups
      tested for the apoptosis-related caspase signals and apoptosis under both in
      vitro and in vivo conditions, Gem/S1/Pomalidomide group demonstrated the
      strongest activation of the caspase signals and proapoptotic effect. In
      Gem/S1/Pomalidomide group, cell proliferation and tumor growth were slower than
      those in other groups both in vitro and in vivo (p < 0.01). There were no obvious
      adverse effects except for thrombocytosis by using pomalidomide. Conclusions:
      Pomalidomide promotes chemosensitization of pancreatic cancer by inhibiting
      chemotherapeutic agents-induced NF-kappaB activation.

PMID- 29632645
TI  - Differential clinicopathological and molecular features within late-onset
      colorectal cancer according to tumor location.
AB  - Background: Since there is a predilection of some clinical and molecular features
      for a given tumor location, we assessed whether this can be confirmed in late
      onset colorectal cancer (LOCRC). Results: Right colon cancers showed features
      associated with sporadic Microsatellite Instability: predominance of female cases
      and BRAF mutations, and an important mucinous component. Left colon cancers
      developed a higher number of polyps and multiple primary CRCs, showed the
      strongest familial component, and had better prognosis. Rectal cancers showed a
      predominantly sporadic phenotype, with worse prognosis and a CpG Island
      Methylator Phenotype (CIMP)-High. No copy number alterations (CNAs) greater than
      or equal to 50% were observed in this LOCRC group, and the most recurrent
      alterations were losses at 5q13 and 14q11, and gains at 7q11, 7q21-q22, 19p13
      p12, 19q13 and 20p11-q11. KRAS and PIK3CA were the only mutated genes showing
      differences according to the tumor location, mainly for right colon cancers.
      Materials and Methods: We analyzed clinical and molecular characteristics of
      LOCRC at different tumor locations in order to determine if there are
      differential phenotypes related with the location in the colon. Conclusions:
      Categorizing LOCRC according to tumor location appears to be an adequate first
      step to resolving the heterogeneity of this subset of CRC.

PMID- 29632646
TI  - Stimulation of medulloblastoma stem cells differentiation by a peptidomimetic
      targeting neuropilin-1.
AB  - Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Despite
      the progress of new treatments, the risk of recurrence, morbidity, and death
      remains important. The neuropilin-1 (NRP-1) receptor has recently been implicated
      in tumor progression of MB, which seems to play an important role in the
      phenotype of cancer stem cells. Targeting this receptor appears as an interesting
      strategy to promote MB stem cells differentiation. Cancer stem-like cells of 3 MB
      cell lines (DAOY, D283-Med and D341-Med), classified in the more pejorative
      molecular subgroups, were obtained by in vitro enrichment. These models were
      characterized by an increase of NRP-1 and cancer stem cell markers (CD15, CD133
      and Sox2), meanwhile a decrease of the differentiated cell marker Neurofilament-M
      (NF-M) was observed. Our previous work investigated potential innovative
      peptidomimetics that specifically target NRP-1 and showed that MR438 had a good
      affinity for NRP-1. This small molecule decreased the self-renewal capacity of MB
      stem cells for the 3 cell lines and reduced the invasive ability of DAOY and D283
      stem cells while NRP-1 expression and cancer stem cell markers decreased at the
      same time. Possible molecular mechanisms were explored and showed that the
      activation of PI3K/AKT and MAPK pathways significantly decreased for DAOY cells
      after treatment. Finally, our results highlighted that targeting NRP-1 with MR438
      could be a potential new strategy to differentiate MB stem cells and could limit
      medulloblastoma progression.

PMID- 29632647
TI  - Metabolic consequences of HIF silencing in a triple negative human breast cancer
      xenograft.
AB  - Hypoxia is frequently encountered in tumors and results in the stabilization of
      hypoxia inducible factors (HIFs). These factors transcriptionally activate genes
      that allow cells to adapt to hypoxia. In cancers, hypoxia and HIFs have been
      associated with increased invasion, metastasis, and resistance to chemo and
      radiation therapy. Here we have characterized the metabolic consequences of
      silencing HIF-1alpha and HIF-2alpha singly or combined in MDA-MB-231 triple
      negative human breast cancer xenografts, using non-invasive proton magnetic
      resonance spectroscopic imaging (1H MRSI) of in vivo tumors, and high-resolution
      1H MRS of tumor extracts. Tumors from all three sublines showed a significant
      reduction of growth rate. We identified new metabolic targets of HIF, and
      demonstrated the divergent consequences of silencing HIF-1alpha and HIF-2alpha
      individually on some of these targets. These data expand our understanding of the
      metabolic pathways regulated by HIFs that may provide new insights into the
      adaptive metabolic response of cancer cells to hypoxia. Such insights may lead to
      novel metabolism based therapeutic targets for triple negative breast cancer.

PMID- 29632648
TI  - Outcomes of ALK positive lung cancer patients treated with crizotinib or second
      generation ALK inhibitor: a monoinstitutional experience.
AB  - Rearrangement in the anaplastic lymphoma kinase (ALK) gene is one of the
      oncogenic drivers in non-small cell lung cancer (NSCLC) patients. Several ALK
      inhibitors (ALKis) have been developed and have demonstrated their efficacy,
      however the best treatment strategy for ALK positive NSCLC patients has yet to be
      determined. Our retrospective study has investigated the outcome of 40 ALK
      rearranged NSCLC patients treated with two different sequential strategies in our
      Institute; a "classical group", treated with crizotinib followed by second or
      third generation ALKis, and the "experimental group", treated upfront with a
      second generation ALK inhibitor. The primary endpoints investigated were
      Progression-free survival (PFS) and intracranial activity. The analysis has
      revealed a significant improvement in PFS (p = 0.050) in the experimental group,
      furthermore none of these patients developed brain metastasis. There was no
      statistically significant difference in OS, but all patients in the experimental
      group were still alive after a median follow up of 15 months. Our retrospective
      analysis suggests that systemic and intracranial efficacy tends to be better in
      the experimental group; randomized prospective studies could confirm our
      observations.

PMID- 29632649
TI  - Circulating miR-106b-3p, miR-101-3p and miR-1246 as diagnostic biomarkers of
      hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the most common liver cancer and second leading
      cause of cancer related death worldwide. Most HCCs occur in a damaged cirrhotic
      background and it may be difficult to discriminate between regenerative nodules
      and early HCCs. No dependable molecular biomarker exists for the early detection
      of HCC. MicroRNAs (miRNAs) have attracted attention as potential blood-based
      biomarkers. To identify circulating miRNAs with diagnostic potential in HCC, we
      performed preliminary RNAseq studies on plasma samples from a small set of HCC
      patients, cirrhotic patients and healthy controls. Then, out of the identified
      miRNAs, we investigated miR-101-3p, miR-106b-3p, miR-1246 and miR-411-5p in
      plasma of independent HCC patients' cohorts. The use of droplet digital PCR
      (ddPCR) confirmed the aberrant levels of these miRNAs. The diagnostic
      performances of each miRNA and their combinations were measured using Receiver
      Operating Characteristic (ROC) curve analyses: a classifier consisting of miR-101
      3p, miR-1246 and miR-106b-3p produced the best diagnostic precision in plasma of
      HCC vs. cirrhotic patients (AUC = 0.99). A similar performance was found when the
      levels of miRNAs of HCC patients were compared to healthy controls (AUC = 1.00).
      We extended the analyses of the same miRNAs to serum samples. In serum of HCC vs.
      cirrhotic patients, the combination of miR-101-3p and miR-106b-3p exhibited the
      best diagnostic accuracy with an AUC = 0.96. Thus, circulating miR-101-3p, miR
      106b-3p and miR-1246, either individually or in combination, exhibit a
      considerable potential value as diagnostic biomarkers of HCC.

PMID- 29632650
TI  - Association between polymorphism rs12722 in COL5A1 and musculoskeletal soft
      tissue injuries: a systematic review and meta-analysis.
AB  - The rs12722 polymorphism in COL5A1 gene has been implicated in the etiology of
      musculoskeletal soft tissue injuries in several association studies with limited
      sample size and conflicting results. The purpose of the present systematic review
      and meta-analysis was to evaluate and synthesize the currently available data on
      the association between rs12722 and musculoskeletal soft tissue injuries. Five
      electronic databases including Pubmed, EMBASE, ISI Web of Science, CNKI and
      Wanfang were searched to identify relevant studies published before 15 May, 2017.
      Summary odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs)
      were estimated using the RevMan 5.3 software. Nine studies comprising 1140 cases
      and 1410 healthy controls met the eligibility criteria. Recessive model was
      confirmed to be the optimum model (TT vs TC + CC). The results indicated that
      rs12722 SNP was significantly associated with musculoskeletal soft tissue
      injuries (OR 1.58, 95% CI 1.33, 1.89; P < 0.00001). When stratified by injury
      sites, modest but statistically significant association was found in Achilles
      tendon pathology (ATP), anterior cruciate ligament injuries (ACLI) and tennis
      elbow (TE). Subgroup-analysis by ethnicity suggested that TT genotype of rs12722
      was associated with tendon and ligament injuries in Caucasians (OR 1.59, 95% CI
      1.33, 1.90; P < 0.00001) but not in Asians (OR 1.46, 95% CI 0.46, 4.60; P =
      0.52). Our findings indicated that rs12722 of COL5A1 was positively associated
      with tendon and ligament injuries, especially in Caucasian subjects. Individuals
      with TT genotype were predisposed to higher risk of ATP, ACLI and TE.

PMID- 29632651
TI  - Cancer risks in recipients of renal transplants: a meta-analysis of cohort
      studies.
AB  - Renal transplantation is associated with an increased risk of cancers at multiple
      sites; however, the relationships between increased cancer risk and participant
      characteristics remain unclear. We searched PubMed, Embase, and the Cochrane
      Library to identify prospective observational studies performed up to July 2017.
      Totally 11 prospective studies reported data on 79,988 renal transplant
      recipients were included. Renal transplant recipients were found to display a
      higher risk of all cancers (standard incidence ratio [SIR]: 2.89; 95% CI: 2.13
      3.91; P < 0.001), gastric cancer (SIR: 1.93; 95% CI: 1.60-2.34; P < 0.001), colon
      cancer (SIR: 1.85; 95% CI: 1.53-2.23; P < 0.001), pancreatic cancer (SIR: 1.53;
      95% CI: 1.23-1.91; P < 0.001), hepatocellular carcinoma (SIR: 2.45; 95% CI: 1.63
      3.66; P < 0.001), lung cancer (SIR: 1.68; 95% CI: 1.29-2.19; P < 0.001), thyroid
      cancer (SIR: 5.04; 95% CI: 3.79-6.71; P < 0.001), urinary bladder cancer (SIR:
      3.52; 95% CI: 1.48-8.37; P = 0.004), renal cell cancer (SIR: 10.77; 95% CI: 6.40
      18.12; P < 0.001), non-melanoma skin cancer (SIR: 12.14; 95% CI: 6.37-23.13; P <
      0.001), melanoma (SIR: 2.48; 95% CI: 1.08-5.67; P = 0.032), Hodgkin's lymphoma
      (SIR: 4.90; 95% CI: 3.09-7.78; P < 0.001), non-Hodgkin lymphoma (SIR: 10.66; 95%
      CI: 8.54-13.31; P < 0.001), lip cancer (SIR: 29.45; 95% CI: 17.85-48.59; P <
      0.001), breast cancer (SIR: 1.11; 95% CI: 1.00-1.24; P = 0.046), and ovarian
      cancer (SIR: 1.60; 95% CI: 1.23-2.07; P < 0.001). However, renal transplantation
      did not significantly influence the risks of uterine cancer (P = 0.171), and
      prostate cancers (P = 0.188). Our findings suggest that patients who receive
      renal transplantation have an increased risk of cancer at most sites, apart from
      uterine and prostate cancers patients.

PMID- 29632652
TI  - Prevalence of human papillomavirus genotypes and relative risk of cervical cancer
      in China: a systematic review and meta-analysis.
AB  - High-risk HPV (hrHPV) is related to cervical carcinogenesis, although clinical
      data comparing the natural history and carcinogenic potential of type-specific
      HPV remain limited. Furthermore, the nationwide prevalence rates of overall and
      type-specific HPV among women with cervical precancerous lesions and cancer have
      not been reported. Here, a meta-analysis was performed for type-specific HPV
      distribution among 30,165 HPV-positive women, including 12,094 invasive cervical
      cancers (ICCs), 10,026 cervical intraepithelial neoplasia grade 2/3 (CIN2/3),
      3246 CIN1, and 4799 normal cervices from 45 PCR-based studies. We found that
      HPV16 was the most common hrHPV type involved in cervical disease. The HPV16
      positivity rate varied little across normal (22.7%) and CIN1 individuals (23.6%)
      but increased through the CIN2 (37.6%) and CIN3 patients (51.9%) to 65.6% in ICC
      cases. HPV16, 18, 35, 39, 45, and 59 were more frequent in ICC than CIN3, with
      ICC:CIN3 ratios ranging from 2.3 for HPV18 to 1.1 for HPV35/45. HPV31, 33, 52,
      and 58 were more frequent in CIN3 compared with normal cervices but less common
      in ICC compared with CIN3 (ICC:CIN3 ratios ranging from 0.6 for HPV58 and 0.4 for
      HPV52). The ICC:normal ratios were particularly high for HPV18, 52 and 58 in West
      China (4.1, 3.9 and 2.9, respectively) and for HPV45 and 59 in North China (1.6
      and 1.1, respectively). In summary, this study is the most comprehensive analysis
      of type-specific HPV distribution in cervical carcinogenesis and could be
      valuable for HPV-based cervical cancer screening strategies and vaccination
      policies in China.

PMID- 29632653
TI  - The therapeutic effect of splenectomy plus selective pericardial
      devascularization versus conventional pericardial devascularization on portal
      hypertension in China: a meta-analysis.
AB  - Background: To systematically review perioperative outcomes and postoperative
      complications between splenectomy plus s-EGDV and n-sEGDV for portal hypertension
      complicated with thoracic esophageal varices and bleeding by a meta-analysis.
      Method: We searched the databases of PubMed, the Cochrane Library, Web of
      Science, EMBASE, TCGA, Chinese Biomedicine Database from January 2000 to June
      2017, and included studies that compared perioperative outcomes and postoperative
      complications between s-EGDV and n-sEGDV. These included studies were assessed by
      two independent investigators. Results: Seven randomized controlled trials (RCTs)
      and seven non-randomized observational clinical studies (OCS) were included. The
      s-EGDV was more beneficial than n-sEGDV in reducing the PVF (OR = 4.26; 95% CI,
      2.81-5.71; P < 0.00001; I2 = 97% for heterogeneity), portal vein flow (OR = 
      111.75; 95% CI, -197.13-26.38; P = 0.01; I2 = 90% for heterogeneity), portal
      hypertensive gastropathy(OR = 0.38; 95% CI, 0.28-0.51; P < 0.00001; I2 = 0% for
      heterogeneity), hepatic encephalopathy (OR = 0.40; 95% CI, 0.23-0.71; P = 0.002;
      I2 = 22% for heterogeneity), postoperative re-bleeding (OR = 0.43; 95% CI, 0.29
      0.63; P < 0.0001; I2 = 9% for heterogeneity), postoperative mortality (OR = 0.52;
      95% CI, 0.32-0.85; P = 0.009; I2 = 0% for heterogeneity) and in increasing
      hepatic artery flow (OR = 92.53; 95% CI, 9.60-175.46; P = 0.03; I2 = 95% for
      heterogeneity). Conclusion: sEGDV offers a more effective surgical approach with
      fewer complications to treat portal hypertension than n-sEGDV. Upon further
      detailed analysis of the surgical indications and hemodynamic and postoperative
      major complications of selective devascularization, sEGDV likely will provide us
      with a new direction in the choice of surgical approach for portal hypertension.

PMID- 29632654
TI  - Clinical features and management of nonfunctioning giant pituitary adenomas
      causing hydrocephalus.
AB  - We evaluated the features of clinically nonfunctioning giant pituitary adenomas
      (NFGPAs) causing hydrocephalus to highlight the timing of hydrocephalus
      management and surgical approaches. A total of 24 patients with NFGPAs and
      hydrocephalus were included. Eighteen patients underwent endoscopic
      transsphenoidal surgery. Ten patients received pterional surgery, including 6
      patients as first treatment and 4 cases with recurrence after transsphenoidal
      approach. Gross total resection was achieved in 10 patients, including 6 cases
      (6/18, 33.3%) with endoscopic transsphenoidal surgery and 4 cases (4/10, 40%)
      with pterional surgery. All patients were divided into preoperative EVD group and
      non-preopoerative EVD group. The proportion of patients receiving postoperative
      EVD or shunt was significantly higher in non-preoperative EVD group than that in
      preoperative EVD group (9/15 vs. 1/9, P = 0.033). Visual impairment score (VIS)
      was evaluated for each patient. We detected significant vision improvement
      according to the preoperative and postoperative VIS (median, interquartile range:
      62, 48.25-77 vs. 36.5, 0-50.75, P < 0.001). Conclusively, for patients with
      NFGPAs and hydrocephalus, preoperative EVD might reduce the need for a second
      shunt or EVD. Surgical approach should be decided based on the
      clinicoradiological features and surgeons' experience for individualized
      treatment, and endoscopic transsphenoidal resection of pituitary adenomas was
      suggested for most NFGPAs.

PMID- 29632656
TI  - Correction: Efficacy of transcatheter arterial chemoembolization for liver
      metastases arising from pancreatic cancer.
AB  - [This corrects the article DOI: 10.18632/oncotarget.14642.].

PMID- 29632655
TI  - Novel approaches against epidermal growth factor receptor tyrosine kinase
      inhibitor resistance.
AB  - Background: The identification and characterization of molecular biomarkers has
      helped to revolutionize non-small-cell lung cancer (NSCLC) management, as it
      transitions from target-focused to patient-based treatment, centered on the
      evolving genomic profile of the individual. Determination of epidermal growth
      factor receptor (EGFR) mutation status represents a critical step in the
      diagnostic process. The recent emergence of acquired resistance to "third
      generation" EGFR tyrosine kinase inhibitors (TKIs) via multiple mechanisms serves
      to illustrate the important influence of tumor heterogeneity on prognostic
      outcomes in patients with NSCLC. Design: This literature review examines the
      emergence of TKI resistance and the course of disease progression and,
      consequently, the clinical decision-making process in NSCLC. Results: Molecular
      markers of acquired resistance, of which T790M and HER2 or MET amplifications are
      the most common, help to guide ongoing treatment past the point of progression.
      Although tissue biopsy techniques remain the gold standard, the emergence of
      liquid biopsies and advances in analytical techniques may eventually allow "real
      time" monitoring of tumor evolution and, in this way, help to optimize targeted
      treatment approaches. Conclusions: The influence of inter- and intra-tumor
      heterogeneity on resistance mechanisms should be considered when treating
      patients using resistance-specific therapies. New tools are necessary to analyze
      changes in heterogeneity and clonal composition during drug treatment. The
      refinement and standardization of diagnostic procedures and increased
      accessibility to technology will ultimately help in personalizing the management
      of NSCLC.

PMID- 29632657
TI  - Ordering Protein Contact Matrices.
AB  - Numerous biophysical approaches provide information about residues spatial
      proximity in proteins. However, correct assignment of the protein fold from this
      proximity information is not straightforward if the spatially close protein
      residues are not assigned to residues in the primary sequence. Here, we propose
      an algorithm to assign such residue numbers by ordering the columns and lines of
      the raw protein contact matrix directly obtained from proximity information
      between unassigned amino acids. The ordering problem is formatted as the search
      of a trail within a graph connecting protein residues through the nonzero contact
      values. The algorithm performs in two steps: (i) finding the longest trail of the
      graph using an original dynamic programming algorithm, (ii) clustering the
      individual ordered matrices using a self-organizing map (SOM) approach. The
      combination of the dynamic programming and self-organizing map approaches
      constitutes a quite innovative point of the present work. The algorithm was
      validated on a set of about 900 proteins, representative of the sizes and
      proportions of secondary structures observed in the Protein Data Bank. The
      algorithm was revealed to be efficient for noise levels up to 40%, obtaining
      average gaps of about 20% at maximum between ordered and initial matrices. The
      proposed approach paves the ways toward a method of fold prediction from noisy
      proximity information, as TM scores larger than 0.5 have been obtained for ten
      randomly chosen proteins, in the case of a noise level of 10%. The methods has
      been also validated on two experimental cases, on which it performed
      satisfactorily.

PMID- 29632658
TI  - Unicentric epithelioid hemangioendothelioma of the calcaneus: a case report and
      review of literature.
AB  - Background: This review of the literature combined with a clinical case will
      allow the illustration of a favorable outcome of this variable low grade
      malignancy, display a role for limb salvage surgery with intralesional treatment,
      and offer a clinical example of epithelioid hemangioendothelioma, a rare
      malignancy. Case presentation: The case report presents a case of solitary
      epithelioid hemangioendothelioma (EHE) of the calcaneus in a 60-year-old male.
      Primary vascular tumors of the bone are rare; however, EHE is one of the most
      common primary malignant vascular tumors to occur in bone. A review of the
      literature found few cases that involved the calcaneus; those cases found that
      involved the calcaneus were either part of a multifocal or metastatic disease
      process. Our case presents a 45-month clinical follow-up of solitary EHE in the
      calcaneus treated with surgical excision by curettage and cementing. Conclusion:
      This case has clinical follow-up greater than 2 years post-operatively and could
      be a guide for treatment of a rare disorder with a substantial paucity of
      literature.

PMID- 29632659
TI  - INAVA promotes aggressiveness of papillary thyroid cancer by upregulating MMP9
      expression.
AB  - Background: Innate immunity activator (INAVA) has been shown to be elevated in
      lung adenocarcinoma. However, its expression pattern and function in papillary
      thyroid cancer (PTC) are unknown. This study aimed to identify the clinical,
      biological, and mechanistic impacts of INAVA on PTC. Methods: Using The Cancer
      Genome Atlas dataset, real time PCR, and immunohistochemistry, the expression of
      INAVA in PTC was analyzed. Gain- and loss-of-function assays were performed to
      investigate the role of INAVA in PTC cell invasion, migration, and metastasis. We
      explored the molecular mechanisms underlying the roles of INAVA in PTC cells
      using transcriptome resequencing, real time PCR, western blotting and
      immunohistochemistry. Results: We found that INAVA expression was significantly
      upregulated in PTC and was significantly associated with lymph node metastasis.
      Loss- and gain-of-function experiments demonstrated that INAVA promoted the
      aggressive phenotype of PTC cells in vitro and in vivo. Mechanistic study
      suggested that upregulation of INAVA resulted in elevated fibroblast growth
      factor 1 (FGF1), which in turn increased the expression level of matrix
      metalloproteinases 9 (MMP9). We further identified that the level of INAVA was
      positively correlated with the levels of FGF1 and MMP9 in clinical PTC specimens.
      Conclusion: These data establish a novel role for INAVA in promoting PTC
      progression and suggest that INAVA may represent a therapeutic target for the
      disease.

PMID- 29632660
TI  - Ghrelin therapy mitigates bone marrow injury and splenocytopenia by sustaining
      circulating G-CSF and KC increases after irradiation combined with wound.
AB  - Background: Radiation injury combined wound (CI) enhances acute radiation
      syndrome and subsequently mortality as compared to radiation injury alone (RI).
      We previously reported that ghrelin (a 28-amino-acid-peptide secreted from the
      stomach) treatment significantly increased a 30-day survival, mitigated
      hematopoietic death, circulating white blood cell (WBC) depletion and
      splenocytopenia and accelerated skin-wound healing on day 30 after CI. Herein, we
      aimed to study the ghrelin efficacy at early time points after CI. Methods:
      B6D2F1/J female mice were exposed to 60Co-gamma-photon radiation at 9.5 Gy
      (LD50/30) followed by a 15% total-body-surface-area skin wound. Several endpoints
      were measured at 4-5 h, days 1, 3, 7 and 15. Results: Histological analysis of
      sternums on day 15 showed that CI induced more adipocytes and less megakaryocytes
      than RI. Bone marrow cell counts from femurs also indicated CI resulted in lower
      bone marrow cell counts on days 1, 7 and 15 than RI. Ghrelin treatment mitigated
      these CI-induced adverse effects. RI and CI decreased WBCs within 4-5 h and
      continued to decrease to day 15. Ghrelin treatment mitigated decreases in CI
      mice, mainly from all types of WBCs, but not RBCs, hemoglobin levels and
      hematocrit values. Ghrelin mitigated the CI-induced thrombocytopenia and
      splenocytopenia. CI increased granulocyte-colony stimulating factor (G-CSF) and
      keratinocyte chemoattractant (KC) in blood and bone marrow. Ghrelin therapy was
      able to enhance and sustain the increases in serum on day 15, probably
      contributed by spleen and ileum, suggesting the correlation between G-CSF and KC
      increases and the neutropenia mitigation. Activated caspase-3 levels in bone
      marrow cells were significantly mitigated by ghrelin therapy on days 3 and 15.
      Conclusions: Our novel results are the first to suggest that ghrelin therapy
      effectively decreases hematopoietic death and splenocytopenia by sustaining
      circulating G-CSF and KC increases after CI. These results demonstrate efficacy
      of ghrelin as a radio-mitigator/therapy agent for CI.

PMID- 29632661
TI  - Effect of chiropractic treatment on primary or early secondary prevention: a
      systematic review with a pedagogic approach.
AB  - Introduction: The chiropractic vitalistic approach to the concept of
      'subluxation' as a cause of disease lacks both biological plausibility and
      possibly proof of validity. Nonetheless, some chiropractors purport to prevent
      disease in general through the use of chiropractic care. Evidence of its effect
      is needed to be allowed to continue this practice. The objective of this
      systematic review was therefore to investigate if there is any evidence that
      spinal manipulations/chiropractic care can be used in primary prevention (PP)
      and/or early secondary prevention in diseases other than musculoskeletal
      conditions. Method: We searched PubMed, Embase, Index to Chiropractic Literature,
      and some specialized chiropractic journals, from inception to October 2017, using
      terms including: "chiropractic", "subluxation", "wellness", "prevention", "spinal
      manipulation", "mortality". Included were English language articles that
      indicated that they studied the clinical preventive effect of or benefit from
      manipulative therapy/chiropractic treatment in relation to PP and/or early
      treatment of physical diseases/morbidity in general, other than musculoskeletal
      disorders. Also, population studies were eligible. Checklists were designed in
      relation to the description of the reviewed articles and some basic quality
      criteria. Outcomes of studies were related to their methodological quality,
      disregarding results from those unable to answer the research questions on effect
      of treatment. Results: Of the 13.099 titles scrutinized, 13 articles were
      included (eight clinical studies and five population studies). These studies
      dealt with various disorders of public health importance such as diastolic blood
      pressure, blood test immunological markers, and mortality. Only two clinical
      studies could be used for data synthesis. None showed any effect of spinal
      manipulation/chiropractic treatment. Conclusion: We found no evidence in the
      literature of an effect of chiropractic treatment in the scope of PP or early
      secondary prevention for disease in general. Chiropractors have to assume their
      role as evidence-based clinicians and the leaders of the profession must accept
      that it is harmful to the profession to imply a public health importance in
      relation to the prevention of such diseases through manipulative
      therapy/chiropractic treatment.

PMID- 29333230
TI  - Funding knowledgebases: Towards a sustainable funding model for the UniProt use
      case.
AB  - Millions of life scientists across the world rely on bioinformatics data
      resources for their research projects. Data resources can be very expensive,
      especially those with a high added value as the expert-curated knowledgebases.
      Despite the increasing need for such highly accurate and reliable sources of
      scientific information, most of them do not have secured funding over the near
      future and often depend on short-term grants that are much shorter than their
      planning horizon. Additionally, they are often evaluated as research projects
      rather than as research infrastructure components. In this work, twelve funding
      models for data resources are described and applied on the case study of the
      Universal Protein Resource (UniProt), a key resource for protein sequences and
      functional information knowledge. We show that most of the models present
      inconsistencies with open access or equity policies, and that while some models
      do not allow to cover the total costs, they could potentially be used as a
      complementary income source. We propose the Infrastructure Model as a sustainable
      and equitable model for all core data resources in the life sciences. With this
      model, funding agencies would set aside a fixed percentage of their research
      grant volumes, which would subsequently be redistributed to core data resources
      according to well-defined selection criteria. This model, compatible with the
      principles of open science, is in agreement with several international
      initiatives such as the Human Frontiers Science Program Organisation (HFSPO) and
      the OECD Global Science Forum (GSF) project. Here, we have estimated that less
      than 1% of the total amount dedicated to research grants in the life sciences
      would be sufficient to cover the costs of the core data resources worldwide,
      including both knowledgebases and deposition databases.

PMID- 29560253
TI  - Evaluation of Trichoderma spp., Pseudomonasfluorescens and Bacillus subtilis for
      biological control of Ralstonia wilt of tomato.
AB  - Background:Ralstonia spp. is a major pathogenic microbe for tomato, which invades
      the roots of diverse plant hosts and colonizes xylem vessels causing wilt,
      especially in tropical, subtropical and warm-temperate regions. Ralstonia spp.
      produces several virulence factors helping it to invade the plant's natural
      defense mechanism. Native isolates of Trichoderma spp., Pseudomonas fluorescens
      and Bacillus subtilis can be used as biocontrol agents to control the bacterial
      wilt and combined application of these beneficial microbes can give better
      results. Methods: Bacterial wilt infection in the field was identified by field
      experts and the infected plant part was used to isolate Ralstonia spp. in CPG
      media and was positively identified. Subsequently, the efficacy of the biocontrol
      agents was tested and documented using agar well diffusion technique and digital
      microscopy. 2ml of the microbial concentrate (10 9 cells/ml) was mixed in one
      liter of water and was applied in the plant root at the rate of 100 ml per plant
      as a treatment method. Results: It was observed that the isolated Trichoderma
      spp. AA2 and Pseudomonas fluorescens PFS were most potent in inhibiting the
      growth of Ralstonia spp. , showing ZOI 20.67 mm and 22.33 mm, respectively.
      Digital microscopy showed distinct inhibitory effect on the growth and survival
      of Ralstonia spp . The results from the field data indicated that Trichoderma
      spp. and Pseudomonas fluorescens alone were able to prevent 92% and 96% of the
      infection and combination of both were more effective, preventing 97% of
      infection. Chemical control methods prevented 94% of infection. Bacillus subtilis
      could only prevent 84 % of the infection.   Conclusions: Antagonistic effect
      against Ralstonia spp. shown by native isolates of Trichoderma spp. and P.
      fluorescens manifested the promising potential as biocontrol agents. Combined
      application gave better results. Results shown by Bacillus subtilis were not
      significant.

PMID- 29623194
TI  - Case Report: Dermoscopic features of oral lichen planus - the evolution of
      mucoscopy.
AB  - Dermoscopy, a non-invasive technique for cutaneous diagnosis is being
      increasingly studied in various disorders of the skin, nails and scalp. However,
      it has been under-utilized for the diagnosis and characterization of mucosal
      disorders. The dermoscopic characterization of cutaneous lichen planus and its
      variants has been well documented with Wickham's striae constituting the hallmark
      of the condition. However, the dermoscopic features of oral lichen planus with
      hand-held or videodermoscopy remain to be elucidated. We present the case of a
      young adult man who presented with asymptomatic white lacy lesions over a bluish
      black background over the tongue, patchy hyperpigmentation of the buccal mucosae
      and gingivae, and longitudinal melanonychia involving some nails. History of
      intake of any drugs preceding the lesions, smoking, chewing of betel nut and
      dental implants was negative. Family history was non-contributory. There were no
      cutaneous lesions suggestive of lichen planus. Mucoscopy (dermoscopy of the
      mucosa, oral in this case) and onychoscopy were done followed by biopsy from the
      tongue that confirmed the diagnosis of lichen planus. Oral mucoscopy of the
      tongue revealed a tri-colored pattern with structureless veil-like grey-white
      areas (modified Wickham's striae), well-demarcated red glossy erosions, and
      violaceous-to-brown clods. Additionally, vascular pattern of dotted and linear to
      curved vessels along the borders of leukoplakia-like areas and erosions were
      observed. Onychoscopy confirmed lichen planus-associated melanonychia. Dermoscopy
      also proved useful in conveniently ruling out other disorders typified by mucosal
      and nail pigmentation such as Laugier Hunziker syndrome and drug-induced changes.
      Although direct oral microscopy has been used in defining features of oral lichen
      planus, to the best of our knowledge this case is the first report on mucoscopy
      or dermoscopy of oral lichen planus.

PMID- 29632665
TI  - An in vitro comparison of standard cleaning to a continuous passive disinfection
      cap for the decontamination of needle-free connectors.
AB  - Background: The optimal decontamination method for needle-free connectors is
      still unresolved. The objective of this study was to determine if a continuous
      passive disinfection cap is as effective as standard cleaning for the microbial
      decontamination of injection ports of two types of needle-free connectors.
      Methods: The injection ports of needle-free connectors were inoculated with
      Staphylococcus aureus and allowed to dry. Disinfection caps containing 70% (v/v)
      isopropyl alcohol (IPA) were attached to the connectors for one, three or 7 days
      and were compared with needle-free connectors cleaned with 2% (w/v) chlorhexidine
      gluconate (CHG) in 70% (v/v) IPA. The number of S. aureus remaining on the
      injection ports was evaluated. Median log10 reductions and 95% confidence
      interval (CI) were calculated and data analyzed using the Mann-Whitney test.
      Results: The application of the disinfection cap resulted in a significantly
      higher reduction in S. aureus than the 2% (w/v) CHG in 70% (v/v) IPA wipe,
      achieving a > 5 Log10 reduction in CFU at each time point. Conclusions: The
      disinfection caps resulted in a significantly higher reduction in S.aureus on the
      injection ports when compared to the use of a 2% (w/v) CHG in 70% (v/v) IPA wipe.
      This offers an explanation for the lower rates of central-line associated
      bloodstream infection (CLABSI) associated with the use of disinfection caps
      reported in clinical studies.

PMID- 29632666
TI  - Isolation of bacteria from fermented food and grass carp intestine and their
      efficiencies in improving nutrient value of soybean meal in solid state
      fermentation.
AB  - Background: Soybean meal is an excellent and cost-effective protein source;
      however, its usage is limited in the piglet due to the presence of anti
      nutritional factors and the antigens glycinin and beta-conglycinin. The objective
      of the current study was to screen and select for bacteria that can be
      efficiently adopted to ferment soybean meal in order to solve this problem.
      Results: Bacteria were isolated from fermented soy foods and the grass carp
      intestine, and strains selected for high protease, cellulase and amylase
      activities. The isolated bacteria were characterized as Bacillus cereus, Bacillus
      subtilis and Bacilus amyloliquefacien, respectively. Fermentation with food
      derived Isolate-2 and fish-derived F-9 increased crude protein content by 5.32%
      and 8.27%, respectively; improved the amino acid profile by increasing certain
      essential amino acids, broke down larger soy protein to 35 kDa and under,
      eliminated antigenicity against glycinin and beta-conglycinin, and removed
      raffinose and stachyose in the soybean meal following a 24-h fermentation.
      Conclusions: Our results suggest these two B. amyloliquefaciens bacteria can
      efficiently solid state ferment soybean meal and ultimately produce a more
      utilizable food source for growing healthy piglets.

PMID- 29632667
TI  - Immune regulation of the unfolded protein response at the mucosal barrier in
      viral infection.
AB  - Protein folding in the endoplasmic reticulum (ER) is subject to stringent quality
      control. When protein secretion demand exceeds the protein folding capacity of
      the ER, the unfolded protein response (UPR) is triggered as a consequence of ER
      stress. Due to the secretory function of epithelial cells, UPR plays an important
      role in maintaining epithelial barrier function at mucosal sites. ER stress and
      activation of the UPR are natural mechanisms by which mucosal epithelial cells
      combat viral infections. In this review, we discuss the important role of UPR in
      regulating mucosal epithelium homeostasis. In addition, we review current
      insights into how the UPR is involved in viral infection at mucosal barriers and
      potential therapeutic strategies that restore epithelial cell integrity following
      acute viral infections via cytokine and cellular stress manipulation.

PMID- 29632668
TI  - Prevalence of cytopenias in both HAART and HAART naive HIV infected adult
      patients in Ethiopia: a cross sectional study.
AB  - Background: In individuals infected with HIV, hematological abnormalities are
      common and are associated with increased risk of disease progression and death.
      However, the profile of hematological abnormalities in HIV infected adult
      patients is not known in Ethiopia. Thus, the aim of this study was to assess the
      hematological manifestations of HIV infection and to identify the factors
      associated with cytopenias in both HAART and HAART naive HIV infected adult
      patients in Ethiopia. Method: We conducted a cross-sectional quantitative study
      of HIV-infected adult patients attending the ART follow-up clinic of Jimma
      University Specialized Hospital in Jimma, Ethiopia, from July 2012 to September
      2012. We used a structured questionnaire to collect socio-demographic and
      clinical information. After interviewing, 4 ml of venous blood was drawn from
      each study subject for hematologic and immunologic parameters. Result: The
      prevalence of anemia, leucopenia, thrombocytopenia and lymphopenia among the
      study individuals were 51.5%, 13%, 11.1% and 5% respectively. Presence of
      opportunistic infection (p = 0.001), use of CPT (p = 0.04) and CD4 count < 200
      cells/MUl (p = 0.002) were associated with an increased risk of anemia.
      Conclusion: Hematologic abnormalities were common in HIV infected adult patients.
      Of the cytopenias anemia was the most common. Use of CPT was independently
      associated with increased risk of anemia and leucopenia. Therefore, large scale
      and longitudinal studies, giving emphasis on the association of CPT and
      cytopenia, are recommended to strengthen and explore the problem in depth.

PMID- 29632669
TI  - Insights into early stage of antibiotic development in small- and medium-sized
      enterprises: a survey of targets, costs, and durations.
AB  - Background: Antibiotic innovation has dwindled to dangerously low levels in the
      past 30 years. Since resistance continues to evolve, this innovation deficit can
      have perilous consequences on patients. A number of new incentives have been
      suggested to stimulate greater antibacterial drug innovation. To design effective
      solutions, a greater understanding is needed of actual antibiotic discovery and
      development costs and timelines. Small and medium-sized enterprises (SMEs)
      undertake most discovery and early phase development for antibiotics and other
      drugs. This paper attempts to gather a better understanding of SMEs' targets,
      costs, and durations related to discovery and early phase development of
      antibacterial therapies. Methods: DRIVE-AB, a project focused on developing new
      economic incentives to stimulate antibacterial innovation, held a European
      stakeholder meeting in February 2015. All SMEs invited to this meeting (n = 44)
      were subsequently sent a survey to gather more data regarding their areas of
      activity, completed and expected development costs and timelines, and business
      models. Results: Twenty-five companies responded to the survey. Respondents were
      primarily small companies each focusing on developing 1 to 3 new antibiotics,
      focused on pathogens of public health importance. Most have not yet completed any
      clinical trials. They have reported ranges of discovery and development out-of
      pocket costs that appear to be less expensive than other studies of general
      pharmaceutical research and development (R&D) costs. The duration ranges reported
      for completing each phase of R&D are highly variable when compared to previously
      published general pharmaceutical innovation average durations. However, our
      sample population is small and may not be fully representative of all relevant
      antibiotic SMEs. Conclusions: The data collected by this study provide important
      insights and estimates about R&D in European SMEs focusing on antibiotics, which
      can be combined with other data to design incentives to stimulate antibacterial
      innovation. The variation implies that costs and durations are difficult to
      generalize due to the unique characteristics of each antibiotic project and
      depend on individual business strategies and circumstances.

PMID- 29632670
TI  - Tracheal growth assessment in mongrel puppies (dogs) through multidetector CT.
AB  - The aim of this study was to describe the tracheal growth pattern and its
      zoometric relationship in related medium-sized mongrel puppies through adulthood.
      Fourteen puppies were studied. CT monitoring was performed monthly, starting in
      the 1st month of life through the 7th month and subsequently at the 9th and 12th
      months. Additionally, six zoometric measurements were performed. Dorsoventral
      (DV) and transverse (TV) diameters and the luminal area from C1 to T2 were
      obtained. The global tracheal growth pattern revealed an increase up to 13 times
      its initial size, reaching a plateau phase during the last trimester. The
      relationship between the DV and the TV internal diameters of the tracheal lumen
      did not change during growth. As previously reported, the cranial tracheal area
      was wider, while the caudal part gradually decreased towards T1-T2; this
      consideration is important since the more distal an endotracheal tube is
      inserted, the greater the risk that injury may occur. The linear correlation
      between the zoometric measurements and the tracheal ring areas was positive. This
      study provides evidence for the evaluation of the morphometry of the canine
      trachea during physiological growth using helicoidal CT as a non-invasive,
      accurate tool.

PMID- 29632671
TI  - Cross-sectional area and fat content in dachshund epaxial muscles: an MRI and CT
      reliability study.
AB  - MRI and CT are frequently used to diagnose spinal diseases in dogs. These
      modalities have detected epaxial muscle degeneration in dachshunds with
      intervertebral disc herniation. However, research on the reliability of epaxial
      muscular measurements is limited in veterinary medicine. The aims of the study
      were to assess the intrarater and inter-rater reliability of epaxial muscle cross
      sectional area (CSA) and fat content measurements on MRI and CT images in
      dachshunds, and to compare the CSA measurement between the two modalities. MRI
      and CT images of 10 healthy dachshunds were evaluated. Two blinded observers
      assessed MRI CSA, MRI fat content, CT CSA and CT muscle attenuation of three
      thoracolumbar epaxial muscles using OsiriX. The results showed 'substantial' to
      'almost perfect' intrarater reliability (intraclass correlation coefficient (ICC)
      0.828-0.998) and inter-rater reliability (ICC 0.685-0.854) for all variables.
      When individual spinal segments were analysed, the intrarater and inter-rater
      reliability decreased and the confidence intervals increased. There was positive
      correlation (r= 0.719-0.841, P=0.001) and high agreement (0.824-0.894) for the
      measured CSA between MRI and CT. Epaxial muscle CSA and fat content can be
      reliably measured on MRI and CT, bearing in mind that measurement of certain
      segments requires adequate training.

PMID- 29632672
TI  - Radiographic analysis of the angle in the lateromedial projection of the
      metacarpophalangeal joint and the distal interphalangeal joint in
      metacarpophalangeal flexural deformities in calves.
AB  - The bone alignment of the metacarpophalangeal joint (MPJ) of the distal
      interphalangeal joint (DIPJ) in metacarpophalangeal flexural deformity (MPFD) in
      calves was evaluated by radiography. This study was designed by retrospective
      study of radiographs. Lateral to medial radiographs of distal forelimbs were
      taken from 19 MPFD affected calves (35 forelimbs) and 21 normal calves (42
      forelimbs). Based on the radiographs, the lateral angles of MPJ were measured
      from the metacarpal bone axis and proximal phalanx axis, and lateral angles of
      DIPJ were measured from the middle phalanx axis and distal phalanx axis. Mean
      lateral angle of MPJ in the normal limbs was 175.9 (95% CI 174.5 to 177.4). Mean
      lateral angles of MPJ in MPFD were as follows: mild: 167.1 (158.9-175.2),
      moderate: 165.1 (158.5-171.7) and severe: 150.6 (146-155.1). MPJ angle in MPFD
      limbs was narrower than that in the normal limbs (mild, moderate and severe:
      P=0.017, P=0.003 and P<0.001, respectively). Mean lateral angle of DIPJ in the
      normal limbs was 211.9 (210.7-213.2). Mean lateral angles of DIPJ in moderate:
      200.6 (195.2-206.1) and severe: 204.9 (203.3-206.5) MPFD were narrower than that
      in the normal limbs (both P<0.001). There was no significant difference between
      the normal limbs and mild: 210.3 (206.9-213.7) MPFD limbs (P=0.7). The clinical
      severity of MPFD corresponded well with the lateral angle of MPJ. The flexion of
      DIPJ in moderate and severe MPFD was similar to the flexion of MPJ in MPFD. This
      suggested that the lateral to medial radiographs accurately reflected the MPJ
      flexion and the DIPJ in MPFD in calves, providing useful information for the
      treatment of MPFD.

PMID- 29632673
TI  - Clinical presentation of CIED infection following initial implant versus
      reoperation for generator change or lead addition.
AB  - Objective: To explore differences in clinical manifestations and outcomes in
      those patients who develop infection after undergoing initial implantation versus
      reoperation. Methods: We compared cases of cardiac implantable electronic device
      (CIED) infection based on initial implantation versus reoperation from 11
      centres. Results: There were 432 patients with CIED infection, 178 occurring
      after initial device placement and 254 after repeat reoperation. No differences
      were seen in age, sex or device type. Those with infection after initial implant
      had a higher Charlson Comorbidity Score (median 3 (IQR 2-6) vs 2 (IQR 1-4),
      p<0.001), shorter time since last procedure (median 8.9 months (IQR 0.9-33.3) vs
      19.5 months (IQR 1.1-62.9), p<0.0001) and fewer leads (2.0+/-0.6vs 2.5+/-0.9,
      p<0.001). Pocket infections were more likely to occur after a reoperation
      (70.1%vs48.9%, p<0.001) and coagulase negative staphylococci (CoNS) was the most
      frequently isolated organism in this group (p=0.029). In contrast, initial
      implant infections were more likely to present with higher white cell count
      (10.5+/-5.1 g/dL vs 9.5+/-5.4 g/dL, p=0.025), metastatic foci of infection
      (16.9%vs8.7%, p=0.016) and sepsis (30.9%vs19.3%, p=0.006). There were no
      differences in in-hospital (7.9%vs5.2%, p=0.31) or 6-month mortality
      (21.9%vs14.0%, p=0.056). Conclusions: CIED infections after initial device
      implant occur earlier, more aggressively, and often due to Staphylococcus aureus.
      In contrast, CIED infections after reoperation occur later, are due to CoNS, and
      have more indolent manifestations with primary localisation to the pocket.

PMID- 29632674
TI  - Randomised trial of the comparison of drug-eluting stents in patients with
      diabetes: OCT DES trial.
AB  - Background: To date, there have been limited comparisons performed between
      everolimus-eluting stents (EES) and zotarolimus-eluting stents (ZES) in patients
      with diabetes mellitus (DM). The objectives of this study was to assess the use
      of second-generation drug-eluting stents in patients with DM, using optical
      coherence tomography (OCT) to compare the level of stent coverage of Boston
      Scientific Promus Element EES compared with Medtronic Resolute Integrity
      ZES.(Clinicaltrials.gov number NCT02060357). Methods: This is a single-centre
      randomised blinded trials assessing two commercially available stents in 60
      patients with diabetes (ZES: n=30, EES: n=30). Patients underwent intracoronary
      assessment at 6 months with OCT assessing stent coverage, malapposition,
      neointimal thickness and percentage of in-stent restenosis (ISR). Results: Of the
      60 patients randomised, 46 patients underwent OCT analysis. There was no
      difference in baseline characteristics between the two groups. Both Promus
      Element and Resolute Integrity had low rates of uncovered struts at 6 months with
      no significant difference between the two groups (2.44% vs 1.24%, respectively;
      P=0.17). Rates of malapposition struts (3.9% vs 2.5%, P=0.25) and percentage of
      luminal loss did not differ between stent types. In addition, there was no
      significant difference in major adverse cardiovascular events (P=0.24) between
      the stent types. Conclusions: This study is the first randomised trial to
      evaluate OCT at 6 months for ZES and EES in patients with diabetes. Both stents
      showed comparable strut coverage at 6 months, with no difference in ISR rates at
      6 months.

PMID- 29632675
TI  - Early metabolic response to acute myocardial ischaemia in patients undergoing
      elective coronary angioplasty.
AB  - Objective: Balloon-induced transient coronary ischaemia represents a model of
      myocardial ischaemia and reperfusion. We are interested in the very early
      systemic metabolic response to this event. Methods: Blood samples of patients
      with stable angina (SA) were collected before and after coronary angioplasty.
      Serum metabolic profiles were obtained using nuclear magnetic resonance
      spectroscopy. Univariate and multivariate analyses were used to investigate
      changes in metabolite concentrations. Results: Thirty-four consecutive patients
      with SA, undergoing elective coronary angioplasty at Policlinico Umberto I of
      Rome, were included in this study. Changes in metabolites concentration induced
      by balloon occlusion in venous and arterial sera were detected. In both serum
      types, a significant increase in ketone bodies, 2-hydroxybutyrate, glutamine and
      O-acetylcarnitine concentration is observed, while alanine, lactate,
      phenylalanine and tyrosine decreased after intervention. Most significant
      metabolic changes were detected in arterial serum. Conclusions: Our study points
      out two main global metabolic changes in peripheral blood after balloon-induced
      coronary ischaemia: ketone bodies increase and lactate decrease. Both could be
      related to compensation mechanisms finalised to fulfil heart's needs after short
      period of myocardial ischaemia and probably after reperfusion.

PMID- 29632676
TI  - Role of ivabradine in management of stable angina in patients with different
      clinical profiles.
AB  - In chronic stable angina, elevated heart rate contributes to the development of
      symptoms and signs of myocardial ischaemia by increasing myocardial oxygen demand
      and reducing diastolic perfusion time. Accordingly, heart rate reduction is a
      well-known strategy for improving both symptoms of myocardial ischaemia and
      quality of life (QOL). The heart rate-reducing agent ivabradine, a direct and
      selective inhibitor of the If current, decreases myocardial oxygen consumption
      while increasing diastolic time, without affecting myocardial contractility or
      coronary vasomotor tone. Ivabradine is indicated for treatment of stable angina
      and chronic heart failure (HF). This review examines available evidence regarding
      the efficacy and safety of ivabradine in stable angina, when used as monotherapy
      or in combination with beta-blockers, in particular angina subgroups and in
      patients with stable angina with left ventricular systolic dysfunction (LVSD) or
      HF. Trials involving more than 45 000 patients receiving treatment with
      ivabradine have shown that this agent has antianginal and anti-ischaemic effects,
      regardless of age, sex, severity of angina, revascularisation status or
      comorbidities. This heart rate-lowering agent might also improve prognosis,
      reduce hospitalisation rates and improve QOL in angina patients with chronic HF
      and LVSD.

PMID- 29632677
TI  - GP perceptions of the adequacy of community-based care for patients with advanced
      heart failure in a UK region (NI): a qualitative study.
AB  - Objective: To assess the adequacy of community-based services available in
      Northern Ireland (NI) and to meet the multidimensional needs of patients living
      with New York Heart Association Stage III and IV heart failure (HF), as
      experienced and perceived by general practitioners (GP). Methods: Semistructured
      interviews were conducted with GPs recruited via the University Department of
      General Practice and Northern Ireland Medical and Dental Agency. Interviews were
      transcribed, independently coded and analysed using a six-step thematic analysis
      approach. Results: Twenty semistructured interviews were conducted. GPs reported
      managing patients in a 'reactive rather than proactive' way, responding only to
      acute medical needs, with hospital admission the default option due to lack of
      community-based expertise and services. Care provided by HF specialists was
      highly regarded but 'access and coordination' were lacking, related to inequity
      of access to Heart Failure Nursing Teams, lack of access to specialist advice and
      inadequate handover of information to GPs. Conversations regarding current and
      future care needs and preferences were important, but GPs described 'neglecting
      conversations with the patient', due to time constraints, prognostic uncertainty
      and fear of causing distress. They expressed the view that 'specialist palliative
      care (SPC) is only a credible option in end stages' related to limited
      understanding of the scope of SPC, a perception that timing of referral must
      depend on prognosis and concern that SPC services are cancer-focused.
      Conclusions: Despite the extensive body of research which evidences the unmet
      multidimensional needs of patients with advanced HF, and more recent evidence for
      the effectiveness of integrated SPC in improving quality of life for patients
      with HF, health and social care services within NI have not adapted to assess and
      meet these needs.

PMID- 29632678
TI  - Rise and fall of NT-proBNP in aortic valve intervention.
AB  - Objectives: To describe the dynamics of N-terminal pro-B-type natriuretic peptide
      (NT-proBNP) from preoperative evaluation to 6-month follow-up in patients
      undergoing aortic valve intervention, and to evaluate NT-proBNP with regard to 1
      year mortality. Methods: At preoperative evaluation, we prospectively included
      462 patients accepted for aortic valve intervention. The median time to surgical
      aortic valve replacement (SAVR; n=336) or transcatheter aortic valve implantation
      (TAVI; n=126) was 4 months. NT-proBNP was measured at enrolment for preoperative
      evaluation, on the day of surgery, postoperatively on day 1, day 3 and at the 6
      month follow-up. Subgroups of patients undergoing SAVR with aortic regurgitation
      and aortic stenosis with and without coronary artery bypass were also analysed.
      Results: NT-proBNP remained stable in all subgroups during the preoperative
      waiting period, but displayed a substantial transient early postoperative
      increase with a peak on day 3 except in the TAVI group, which peaked on day 1. At
      the 6-month follow-up, NT-proBNP had decreased to or below the preoperative level
      in all groups. In the SAVR group, NT-proBNP preoperatively and on postoperative
      days 1 and 3 revealed significant discriminatory power with regard to 1-year
      mortality (area under the curve (AUC)=0.79, P=0.0001; AUC=0.71, P=0.03; and
      AUC=0.79, P=0.002, respectively). This was not found in the TAVI group, which had
      higher levels of NT-proBNP both preoperatively and at the 6-month follow-up
      compared with the SAVR group. Conclusions: The dynamic profile of NT-proBNP
      differed between patients undergoing TAVI and SAVR. NT-proBNP in the
      perioperative course was associated with increased risk of 1-year mortality in
      SAVR but not in TAVI.

PMID- 29632679
TI  - CT coronary angiography: a paradigm shift for functional imaging tests.
AB  - The UK National Institute for Health and Care Excellence (NICE) have just updated
      their guideline on new-onset stable chest pain, recommending that all patients
      should be investigated with a CT coronary angiography (CTCA). In a separate
      guideline, NICE recommended CT fractional flow reserve (CT-FFR), to assess
      coronary stenoses, found on CTCA, stating that this would reduce the need for
      invasive coronary angiography and hence reduce cost. We discuss the evidence base
      for CT-FFR and emphasise that we already have established functional imaging
      tests, with extensive evidence base for efficacy and prognosis and that CT-FFR
      should be compared with this standard of care and not with the much more
      expensive and invasive fractional flow reserve undertaken during invasive
      coronary angiography.

PMID- 29632680
TI  - Gender differences in the factors predicting initial engagement at cardiac
      rehabilitation.
AB  - Objective: To determine whether there are gender differences in the factors that
      predict attendance at the initial cardiac rehabilitation baseline assessment (CR
      engagement) after referral. Methods: Using data from the National Audit of
      Cardiac Rehabilitation, we analysed data on 95 638 patients referred to CR
      following a cardiovascular diagnosis/treatment between 2013 and 2016. Eighteen
      factors that have been shown in previous research to be important predictors of
      CR participation were investigated and grouped into four categories:
      sociodemographic factors, cardiac risk factors, patient medical status and
      service-level factors. Logistic binary regression models were built for male
      patients and female patients, assessing the likelihood for CR engagement. Each
      included predictors such as age, number of comorbidities and social deprivation
      score. Results: There were no important differences in the factors that predict
      the likelihood of CR engagement in men and women. Seven factors associated with a
      reduced probability of CR engagement, and eight factors associated with increased
      probability, were identified. Fourteen of the 15 factors identified as predicting
      the likelihood for engagement/non-engagement were the same for both men and
      women. Increasing age, being South Asian or non-white ethnicity (other than
      Black) and being single were all associated with a reduced likelihood of
      attending an initial CR baseline assessment in both men and women. Male patients
      with diabetes were 11% less likely to engage with CR; however, there was no
      significant association in women. Results showed that the overwhelmingly
      important determinant of CR engagement observed in both men and women was
      receiving an invitation to attend an assessment session (OR 4.223 men/4.033women;
      p<0.05). Conclusions: Consideration of gender differences in predictors of CR
      uptake should probably be more nuanced and informed by the stage of the patient
      care pathway.

PMID- 29632681
TI  - Conduction disorders using the Evolut R prosthesis compared with the CoreValve:
      has anything changed?
AB  - Aim: We compared early postprocedural and midterm evolution of atrioventricular
      and intraventricular conduction disorders following implantation of the new
      generation Evolut R (ER) prosthesis in comparison with the previous generation
      CoreValve (CV) system using routinely recorded ECG up to 6-month follow-up.
      Methods: All consecutive patients treated by transcathether aortic valve
      implantation (TAVI) using the Medtronic self-expanding devices for symptomatic
      severe aortic stenosis in a single centre between October 2011 and February 2016
      were considered for inclusion. ECGs recorded at baseline, day 1 after TAVI,
      discharge and 6 months were retrospectively analysed. At each time-point,
      intrinsic rhythm, PR interval, QRS axis and duration, and atrioventricular and
      intraventricular conduction were analysed. Atrioventricular and intraventricular
      conduction following TAVI at discharge and at 6 months were compared intrasubject
      at the different time intervals and between patients receiving the ER versus the
      CV prosthesis. Results: Among the 113 patients included in the analysis (51%
      female, 83.3+/-6.2 years), 60 (53%) patients received the CV and 53 (47%)
      patients received the ER. Compared with patients in the CV group, those in the ER
      group had a lower Society of Thoracic Surgeons score (6.3+/-3.1vs 4.8+/-3.6,
      P=0.02). Patients in the ER group in comparison with those in the CV group more
      frequently had postprocedural PR interval (57%vs23%, respectively, P=0.004) and
      QRS prolongation (76%vs50%, P=0.03) at discharge. Incidence of complete
      atrioventricular block was similar between both groups (9%vs18%, P=0.3) up to 6
      month follow-up. No difference in term of new left bundle branch block (LBBB)
      (34%vs28%, P=0.8) or permanent pacemaker implantation rates (32.1%vs31.7%, P=1.0)
      was reported. Conclusions: Patients with the ER had greater postprocedural
      atrioventricular and intraventricular conduction delays than those with the CV at
      discharge, with however similar incidence of high-degree atrioventricular block,
      new LBBB and permanent pacemaker implantation up to 6-month follow-up.

PMID- 29632682
TI  - A systematic review of interventions targeting men's alcohol use and family
      relationships in low- and middle-income countries.
AB  - Background: Problem drinking accounts for 9.6% of disability-adjusted life years
      worldwide. It disproportionally affects men and has disabling physical,
      psychological, and behavioral consequences. These can lead to a cascade of
      negative effects on men's families, with documented ties to intimate partner
      violence (IPV) and child maltreatment. These multi-level problems are often
      exacerbated where poverty rates are high, including low and middle-income
      countries (LMICs). In contexts where strong patriarchal norms place men in
      positions of power, family-level consequences are often even more pronounced.
      Methods: We conducted a systematic review of the literature on interventions in
      LMICs targeting men's problem drinking and any family-related outcomes. Cochrane
      and PRISMA procedures guided the review. The search was conducted in PsychInfo,
      PubMed, and Web of Science. Results: The search yielded 1357 publications. Nine
      studies from four different countries met inclusion criteria. Of those, only one
      had the primary goal of simultaneously improving drinking and a related family
      level outcome (IPV). Six of the studies documented modest improvements on both
      drinking and couples or family outcomes. Strategies common to these included
      cognitive-behavioral techniques, communication skills training, narrative
      therapy, and participatory learning. Gender-transformative approaches were
      associated with reduced IPV and more equitable gender norms, and motivational
      interviewing and behavioral approaches were beneficial for reducing alcohol use.
      Conclusions: Findings highlight the scarcity of interventions addressing men's
      drinking and its effects on families, particularly for parent-child outcomes.
      However, results point to strategies that, combined with other evidence-based
      family interventions can guide the development and rigorous evaluation of
      integrated programs.

PMID- 29632683
TI  - Community strengthening and mental health system linking after flooding in two
      informal human settlements in Peru: a model for small-scale disaster response.
AB  - Background: Mental health is an important factor in responding to natural
      disasters. Observations of unmet mental health needs motivated the subsequent
      development of a community-based mental health intervention following one such
      disaster affecting Peru in 2017. Methods: Two informal human settlements on the
      outskirts of Lima were selected for a mental health intervention that included:
      (1) screening for depression and domestic violence, (2) children's activities to
      strengthen social and emotional skills and diminish stress, (3) participatory
      theater activities to support conflict resolution and community resilience, and
      (4) community health worker (CHW) accompaniment to government health services.
      Results: A total of 129 people were screened across both conditions, of whom
      12/116 (10%) presented with depression and 21/58 (36%) reported domestic
      violence. 27 unique individuals were identified with at least one problem.
      Thirteen people (48%) initially accepted CHW accompaniment to government-provided
      services. Conclusions: This intervention provides a model for a small-scale
      response to disasters that can effectively and acceptably identify individuals in
      need of mental health services and link them to a health system that may
      otherwise remain inaccessible.

PMID- 29632684
TI  - Surgery for hip preservation-let the patient decide.

PMID- 29632686
TI  - Lateral acetabular coverage as a predictor of femoroacetabular cartilage
      thickness.
AB  - To investigate the correlation between femoroacetabular cartilage thickness and
      lateral acetabular coverage in patients undergoing hip arthroscopy for a variety
      of indications. Articular cartilage at the hip is hypothesized to undergo
      adaptive change secondary to unique patterns of pathomechanical loading which
      results in a direct relationship between acetabular coverage and femoroacetabular
      cartilage thickness. A cohort of 252 patients presenting to our dedicated hip
      preservation service between June 2013 and June 2015 were retrospectively
      analysed. Preoperative radiographs and MRI studies were obtained for all
      symptomatic hips and classified according to radiographic lateral center edge
      angle (LCEA) as follows: normal acetabular coverage (25-40 degrees ), acetabular
      overcoverage (>=40 degrees ), borderline dysplasia (20-24.9 degrees ) and frank
      dysplasia (<20 degrees ). Femoroacetabular cartilage thickness was measured on a
      preoperative MRI-scan at the fovea, middle sourcil, and lateral sourcil. In all
      groups, cartilage thickness was maximized at the lateral sourcil relative to the
      middle sourcil or fovea (P < 0.001). Furthermore, articular cartilage thickness
      was significantly increased when comparing one group to successive groups with
      diminished lateral acetabular coverage. Indeed, multivariate analyses confirmed
      LCEA to be the strongest determinant of femoroacetabular cartilage thickness
      compared with age, gender, body-mass index or presence of cam/pincer lesions.
      Patients with borderline and frank dysplasia exhibit increased values of
      femoroacetabular cartilage thickness in the weight-bearing zone, potentially
      indicating a compensatory reaction to the lack of bony coverage. Articular
      cartilage thickness may serve as an instability marker and inform clinical
      decision-making for patients with borderline dysplasia.

PMID- 29632685
TI  - Imaging of femoroacetabular impingement-current concepts.
AB  - Following the recognition of femoroacetabular impingement (FAI) as a clinical
      entity, diagnostic tools have continuously evolved. While the diagnosis of FAI is
      primarily made based on the patients' history and clinical examination, imaging
      of FAI is indispensable. Routine diagnostic work-up consists of a set of plain
      radiographs, magnetic resonance imaging (MRI) and MR-arthrography. Recent
      advances in MRI technology include biochemically sensitive sequences bearing the
      potential to detect degenerative changes of the hip joint at an early stage prior
      to their appearance on conventional imaging modalities. Computed tomography may
      serve as an adjunct. Advantages of CT include superior bone to soft tissue
      contrast, making CT applicable for image-guiding software tools that allow
      evaluation of the underlying dynamic mechanisms causing FAI. This article
      provides a summary of current concepts of imaging in FAI and a review of the
      literature on recent advances, and their application to clinical practice.

PMID- 29632687
TI  - Outcomes of joint preservation surgery: comparison of patients with developmental
      dysplasia of the hip and femoroacetabular impingement.
AB  - Femoroacetabular impingement (FAI) and developmental dysplasia of the hip (DDH)
      are fundamentally and structurally different hip abnormalities yet their clinical
      presentation can often be very similar. We asked whether adult patients
      surgically treated for DDH when compared with FAI patients achieve (i) better
      outcome as reflected by the WOMAC Osteoarthritis Index, (ii) higher physical
      activity as reflected by the UCLA physical activity scale. Five hundred fifty-six
      patients treated by periacetabular osteotomy for DDH and 540 patients treated for
      FAI (cam, pincer, or combined) in nine high-volume centers, between 2008 and 2011
      were matched using propensity analysis, based on age and BMI. After exclusions,
      144 pairs were evaluated on WOMAC, SF-12 Health Survey, modified Harris Hip Score
      (mHHS) and UCLA scale at pre and post-operations. At pre-operative evaluation,
      FAI patients showed lower scores on WOMAC (total, stiffness, function) and SF-12
      physical. Statistically significant improvements in the outcome scores were
      observed from pre to post-operative time points in both treatment groups. Once
      FAI and DDH patients were compared, FAI patients showed lower scores on most of
      the outcome measures. However, these differences diminished in time, with only SF
      12 mental and mHHS scores remaining significantly lower at 2-year follow-up.
      Because of more advanced disease at presentation, patients with FAI had an
      inferior clinical outcome compared with patients with DDH after surgical
      correction. Further prospective studies are required to better describe the long
      term clinical benefits of hip joint preservation surgery.

PMID- 29632688
TI  - Prospective study of nerve injuries associated with hip arthroscopy in the
      lateral position using the modified portals.
AB  - To access the central compartment of the hip, distraction is essential in hip
      arthroscopy (HA); nerve injuries have long been accepted as a complication of
      this surgical procedure, with an incidence ranging from 0 to 46%. Only one
      previous article collected data prospectively, and the authors utilized a supine
      technique, with a modified mid-anterior portal. Our study also used prospectively
      collected data, from a group of 200 consecutive patients who had HA performed in
      the lateral position using the paratrochanteric portals. Our results were that
      four patients (2%) reported symptoms of neurological deficits after surgery,
      three patients with traction times ranging from 20 to 41 min, their neurological
      deficits resolved completely over a time from 6 to 9 weeks. The fourth patient
      who had the longest traction time of 73 min, and also greater than usual
      traction, his neurological deficit resolved at 12 weeks. Our hypothesis of 200
      hip arthroscopies, performed in the lateral position by the modified
      paratrochanteric portals, the incidence of nerve injuries would be lower than
      46%. We found an incidence of 2%, all affecting the perineum and genitals and all
      occurring in men, no differences between the age, surgery side or type of surgery
      performed on the patient were found to have statistical differences. Traction
      times with <31.5 min were related with fewer incidences of neurological symptoms.
      On the basis of this study, all patients with traction times below 73 min can be
      confidently reassured that any deficit will recover within 3 months.

PMID- 29632689
TI  - The incidence of proximal deep vein thrombosis after elective hip arthroscopy: a
      prospective cohort study in low risk patients.
AB  - Prospectively assess the incidence of deep venous thrombosis (DVT) using Doppler
      Ultrasound, in patients receiving elective hip arthroscopy without
      pharmacologic/mechanical prophylaxis. One hundred and fifteen consecutive
      patients (mean 35.4 years, SD = 10.3) underwent elective hip arthroscopy.
      Patients with previous major risk factors for DVT were excluded. Signs/symptoms
      of DVT/pulmonary embolism were assessed at 2-week post-operatively. A bilateral
      whole leg Duplex color (Doppler) Ultrasonography was scheduled between 10- and 22
      day post-op. The primary outcome was frequency of DVT. Secondary outcomes
      assessed surgical risk factors. One hundred and ten patients (mean = 34.3 years,
      SD = 10.1) did not get a DVT. Five patients (mean = 43.8 years, SD = 12.1) were
      diagnosed with a DVT, 2- to 22-day post-operatively. All DVT patients received
      arthroscopy in the supine position (n = 76), versus no patients in the lateral
      position (n = 39). Average traction time was 38 (SD = 4) and 61 (SD = 4) minutes
      for patients with and without a DVT, respectively. All other a priori defined
      risk factors were similar. Four out of five patients presented with symptoms of a
      DVT, confirmed by ultrasound. One patient was without symptoms/clinical findings.
      Four patients had a DVT restricted to the calf veins; one patient had involvement
      of the popliteal vein. No patients had proximal extension into the thigh or
      pelvis. No pulmonary emboli were suspected or occurred. The incidence of deep
      venous thromboembolism is 4.3%. The majority of patients had symptomatic and
      distal venous thromboembolic events. This study provides supportive evidence that
      routine prophylaxis and/or screening may not be necessary in low risk patients
      undergoing elective hip arthroscopy.

PMID- 29632690
TI  - The feasibility of conducting a randomised controlled trial comparing
      arthroscopic hip surgery to conservative care for patients with femoroacetabular
      impingement syndrome: the FASHIoN feasibility study.
AB  - To determine whether it was feasible to perform a randomized controlled trial
      (RCT) comparing arthroscopic hip surgery to conservative care in patients with
      femoroacetabular impingement (FAI). This study had two phases: a pre-pilot and
      pilot RCT. In the pre-pilot, we conducted interviews with clinicians who treated
      FAI and with FAI patients to determine their views about an RCT. We developed
      protocols for operative and conservative care. In the pilot RCT, we determined
      the rates of patient eligibility, recruitment and retention, to investigate the
      feasibility of the protocol and we established methods to assess treatment
      fidelity. In the pre-pilot phase, 32 clinicians were interviewed, of which 26
      reported theoretical equipoise, but in example scenarios 7 failed to show
      clinical equipoise. Eighteen patients treated for FAI were also interviewed, the
      majority of whom felt that surgery and conservative care were acceptable
      treatments. Surgery was viewed by patients as a 'definitive solution'. Patients
      were motivated to participate in research but were uncomfortable about
      randomization. Randomization was more acceptable if the alternative was available
      at the end of the trial. In the pilot phase, 151 patients were assessed for
      eligibility. Sixty were eligible and invited to take part in the pilot RCT; 42
      consented to randomization. Follow-up was 100% at 12 months. Assessments of
      treatment fidelity were satisfactory. An RCT to compare arthroscopic hip surgery
      with conservative care in patients with FAI is challenging but feasible.
      Recruitment has started for a full RCT.

PMID- 29632691
TI  - Hip arthroscopy for intra-capsular benign tumors: a case series.
AB  - The purpose of this study is to demonstrate the assessment of intra-capsular
      femoral head and neck tumors, and to describe the arthroscopic surgical technique
      used to resect and fill the bone defects. Three cases of benign femoral head and
      neck lesions are presented. Two benign enchondromas and one benign osteochondroma
      were resected arthroscopically. Traction was used in one case. Modified Harris
      Hip Score improved in all three cases to scores of 95 or greater with an average
      improvement of 16 points with a minimum follow up of 15 months. Arthroscopic
      surgical resection of intra-capsular femoral hip lesions offers an effective
      alternative to open resection. This technique offered good outcomes in the
      limited cohort. We suggest that arthroscopic resection of intra-capsular femoral
      hip lesions be considered in relevant cases as an alternative to open resection.

PMID- 29632692
TI  - Multicenter outcomes of arthroscopic surgery for femoroacetabular impingement in
      the community hospital setting.
AB  - The purpose of this study is to determine multi-center outcomes from arthroscopic
      surgery for femoroacetabular impingement in the community hospital setting. A
      prospective design with 2-year minimum follow-up using the nonarthritic hip score
      (NAHS), a 100-point scale of perceived post-operative change for pain, activities
      of daily living, sports activities, and patient satisfaction was implemented at
      three community hospitals. Of 150 enrolled patients (159 hips) with mean age of
      40 years (range, 12-73), there was 81% participation. Mean NAHS at preoperative
      was 54.9, 3 months: 66.6, 12 months: 74.9 and 24 months: 75.4. This represents a
      20.5-point improvement in NAHS (P < 0.001). On the 100-point scale, pain was
      rated +73.5, ADL's: +76.2 and sports: +68.6. 64% of patients were satisfied with
      their surgical outcome. Conversion arthroplasty rate was 8.8% and complication
      rate was 2.5%. In conclusion, arthroscopic surgery for symptomatic
      femoroacetabular impingement in the community setting provides safe and
      successful outcomes.

PMID- 29632693
TI  - The morphologic characteristics and range of motion in the hips of athletes and
      non-athletes.
AB  - The cam deformity may cause impingement and probably leads to osteoarthritis of
      the hip. The aetiology of the cam deformity is incompletely understood. Vigorous
      training during skeletal growth can lead to the development of cam and symptoms
      of femoro-acetabular impingement and subsequent osteoarthritis of the hip. The
      purpose of this study was to compare the radiographic characteristics and range
      of motion between a group of athletes and a non-athletic control group. Thirty
      two male athletes (17 soccer players and 15 ice-hockey players) and thirty non
      athletes, used as a control group, were examined clinically and radiographically.
      Hip range of motion was measured and the FADIR and FABER tests were performed.
      Standard radiographs of both hips were taken. The centre-edge angle, alpha angle,
      caput-collum-diaphysis angle, head-neck offset and Tonnis grade were registered.
      The athletes had a higher Tonnis grade (right P =  0.009, left P =  0.004), more
      pain on the FADIR test (right P =  0.006, left P =  0.001) and lower ROM in
      internal (right P =  0.003, left P =  0.025) and external rotation (P < 0.001). A
      superiorly placed cam deformity (seen on an AP pelvis view) was correlated with
      reduced external rotation (right P =  0.001, left P =  0.004) and mild
      osteoarthritis (Tonnis grade 1), (P =  0.015, left P =  0.020), while a more
      anteriorly placed cam deformity (seen on a modified Lauenstein view) was
      correlated with reduced internal rotation (right P =  0.029, left P =  0.013). A
      lower range of motion, more osteoarthritic changes and more pain were found in
      the athletes than the controls. The control group had more cam deformities than
      previously reported.

PMID- 29632694
TI  - Does the femoral head/neck contour in the skeletally mature change over time?
AB  - The purpose of this study was to determine whether anterior/anterolateral femoral
      head/neck contour of the hip is static or dynamic over time within the context of
      the cam deformity. From a previously published cohort of 200 asymptomatic
      patients who had a magnetic resonance imaging (MRI) of their hips, 23 patients
      were randomly selected: 10 with a cam lesion and 13 with no evidence of a cam
      lesion in either hip. There were 7 females and 16 males with a mean age of 37.5
      years (range 30-56 years). A repeat MRI or computed tomography scan was
      performed. Femoral head/neck contour was assessed with alpha angle measurements
      at the 3 and 1:30 positions. At mean time of 5.3 years (range 2.5-7.2 years)
      between the two time points, the mean alpha angle for the entire cohort was not
      significantly different with alpha angle of 43.4 degrees /53.7 degrees 
      (3:00/1:30 positions) at first visit and 46.1 degrees /54.2 degrees  (3:00/1:30
      positions) at second visit, respectively. Subdividing the cohort into cam
      negative and cam positive groups, there are no clinically relevant differences
      (i.e. <5 degrees ) between the two alpha angle measurements. Inter-observer
      reliability had an intra-class coefficient at 0.96 (95% CI: 0.94-0.97). Neither
      group of patients demonstrated clinically relevant change in the alpha angle.
      Consequently, screening at time of skeletal of maturity would be an efficient
      means of identifying individuals for a possible cam deformity.

PMID- 29632695
TI  - Pre-operative lumbar plexus block provides superior post-operative analgesia when
      compared with fascia iliaca block or general anesthesia alone in hip arthroscopy.
AB  - The objective of this study is to retrospectively examine the effects of pre
      operative fascia iliaca (FI) and lumbar plexus (LPB) nerve blocks on post
      operative pain and secondary post-operative variables following arthroscopic
      surgery of the hip. Subjects undergoing arthroscopic surgery of the hip received
      one of three pre-operative anesthetic techniques; general anesthesia only,
      general anesthesia with FI or general anesthesia with LPB. Patient reported pain
      scores (0-10) were recorded at 0, 30, 60, 90 and 120 min after admission to the
      post-anesthesia care unit (PACU). Secondary variables examined include time spent
      in the PACU, morphine equivalent administered, presence of nausea, persistent
      numbness, parasthesia, weakness, increased narcotic usage for rebound pain, ED
      visits and hospital admissions. The mean pain scores over all time points were
      significantly lower in the LPB group (2.38) than the FI group (4.08, P < 0.001)
      and the Gen group (3.55, P < 0.001). Patients receiving a lumbar plexus block
      exhibited significantly decreased pain at t = 0 (P = 0.019), t = 30 (P = 0.038),
      t = 60 (P = 0.013), t = 90 (P = 0.017) and t = 120 (P = 0.001) after admission to
      PACU. The FI group showed no improvement in any post-operative variable when
      compared with general anesthesia alone. There was no difference in the time to
      discharge or in morphine equivalent administered between groups. One patient
      receiving a lumbar plexus block experienced a seizure lasting about 10 s.
      However, there were no medium or long-term complications. Lumbar plexus block
      administered in concert with general anesthesia provides clinically important and
      statistically significant post-operative pain relief when compared with general
      anesthesia alone or general anesthesia plus fascia iliaca block.

PMID- 29632696
TI  - Defining the greater trochanter-ischial space: a potential source of extra
      articular impingement in the posterior hip region.
AB  - The purpose of this study was to describe greater trochanteric-ischial
      impingement and the relative position of the hip joint where impingement occurs.
      Twenty-three hips from 13 embalmed cadavers (seven males and six females) with a
      lifespan ranging between 46 and 91 years were used for this study. The pelvic
      region of each cadaver was skeletonized leaving only the hip capsule and the
      sciatic nerve. From 90 degrees  of flexion, the hip was extended while
      maintaining a position of 30 degrees  abduction and 60 degrees  external
      rotation. The position of hip flexion was recorded when there was contact between
      the greater trochanter and the ischium. The procedure was repeated in 0 degrees 
      abduction. A Flexion-Abduction-External Rotation (FABER) test was then performed
      on all specimens with a positive finding defined as contact between the greater
      trochanter and the ischium. In 30 degrees  abduction, contact of the ischium and
      the greater trochanter occurred in 87% (20/23) of the hips at an average of 47
      degrees  of flexion (SD 10; range 20-60 degrees ). In 0 degrees  abduction, a
      positive finding was noted in 39% (9/23) of hips at an average of 59 degrees 
      flexion (SD 6; range 52-70 degrees ). A positive finding in the FABER test
      position was noted in 96% (22/23) of hips. The greater trochanter can impinge on
      the ischium when the hip is extended from 90 degrees  flexion in a 60 degrees 
      externally rotated position. This impingement occurred more commonly when the hip
      was in 30 degrees  abduction compared with neutral abduction. The FABER test
      position consistently created greater trochanteric-ischial impingement.

PMID- 29632698
TI  - What the papers say.

PMID- 29632697
TI  - Arthroscopic reconstruction of the Ligamentum Teres: a case series in four
      patients with connective tissue disorders and generalized ligamentous laxity.
AB  - This study presents the results of four Ligamentum Teres (LT) reconstruction
      procedures for hip instability with an average of 21.4 months follow-up (range
      16.4-27.8). The indication for reconstruction was patients who complained of hip
      instability (hip giving way on gait or activities of daily living) on a
      background of a connective tissue disorder and generalized ligamentous laxity.
      The following data were recorded: age, sex, body mass index, hip range of motion,
      impingement signs, acetabular coverage (lateral center edge angle and acetabular
      inclination), acetabular retroversion (ischial spine sign and a crossover sign),
      femoral alpha angles and femoral neck shaft angles. Four patient recorded
      outcomes (PROs) were collected at 3 months, 12 months and 24 months. Three
      patients were female. Three out of four procedures had an improvement in PROs.
      One patient with bilateral procedures had an improvement in PROs on one side at 1
      year but a failure of the graft on the contralateral side. There were no
      complications reported with the technique. LT reconstruction and concomitant
      capsular plication in this case series is associated with an improvement in
      outcomes in three out of four of the patients with hip instability associated
      with a full thickness tear of the LT and who presented with hip instability on a
      background of generalized ligamentous laxity and a connective tissue disorder.
      However, the physical examination, radiographic and intra-operative findings
      which may help predict who would benefit from LT reconstruction require further
      investigation.

PMID- 29632699
TI  - Implementing the World Health Organization safe childbirth checklist in a
      district Hospital in Rwanda: a pre- and post-intervention study.
AB  - Background: Worldwide maternal mortality remains high, with approximately 830
      maternal deaths occurring each day. About 90% of these deaths occur in low-income
      countries. Evidenced-based essential birth practices administered during routine
      obstetrical care and childbirth are key to reducing maternal and neonatal deaths.
      The WHO Safe Childbirth Checklist (SCC) is a low-cost tool designed to ensure
      birth attendants perform 29 essential birth practices (EBP) at four critical
      periods in the birth continuum. This study aimed to evaluate compliance with EBP
      in Masaka District Hospital both before and after the implementation of the WHO
      SCC. Methods: This quality improvement project took place in the Masaka District
      Hospital in Rwanda. Observations of the 29 EBPs were done before and after WHO
      SCC implementation. The implementation process consisted of providing training in
      the use of the checklist to all clinical staff and posting SCC posters at
      different locations in the maternity unit. Results: A total 391 birth events were
      observed pre-intervention and 389 post-intervention. The overall EBP compliance
      rate increased from 46% pre-intervention to 56% post-intervention (P = 0.005).
      Significant improvements were seen in 11 out of 29 EBPs. Conclusion: The
      implementation of the WHO SCC improved the overall EBP compliance rate in Masaka
      District Hospital. Determining the root cause of low compliance rate of some EBP
      may allow for more successful implementation of EBP interventions in the future.
      After further study, the SCC should be considered for scale up.

PMID- 29632700
TI  - Zika virus infection in a pregnant Canadian traveler with congenital fetal
      malformations noted by ultrasonography at 14-weeks gestation.
AB  - Background: Following emergence of Zika virus in the Americas, a devastating new
      congenital syndrome has been documented, leading to significant morbidity among
      Zika-infected fetuses and neonates. Case presentation: A 29-year-old pregnant
      woman infected with Zika virus at 9-weeks gestation in Trinidad presented with
      one-month of fever, headache, and myalgia with persistent viremia. Significant
      fetal abnormalities were identified at 14-week ultrasound, which is the earliest
      ultrasound to describe a severely affected fetus following Zika virus infection
      to our knowledge. Conclusions: We discuss the implications of prolonged maternal
      viremia and the spectrum of congenital Zika syndrome detectable by fetal
      ultrasound.

PMID- 29632701
TI  - Viral and bacterial investigations on the aetiology of recurrent pig neonatal
      diarrhoea cases in Spain.
AB  - Background: Neonatal diarrhoea represents a major disease problem in the early
      stages of animal production, increasing significantly pre-weaning mortality and
      piglets weaned below the target weight. Enteric diseases in newborn piglets are
      often of endemic presentation, but may also occur as outbreaks with high
      morbidity and mortality. The objective of this study was to assess the frequency
      of different pathogens involved in cases of recurrent neonatal diarrhoea in
      Spain. Results: A total of 327 litters from 109 sow farms located in Spain with
      neonatal recurrent diarrhoea were sampled to establish a differential diagnosis
      against the main enteric pathogens in piglets. In total, 105 out of 109 (96.3%)
      case submissions were positive to one of the examined enteric organisms
      considered potentially pathogenic (Escherichia coli, Clostridium perfringens
      types A and C, Transmissible gastroenteritis virus [TGEV], Porcine epidemic
      diarrhoea virus [PEDV] or Rotavirus A [RVA]). Fifty-eight out of 109 (53.2%)
      submissions were positive for only one of these pathogens, 47 out of 109 (43.1%)
      were positive for more than one pathogen and, finally, 4 out of 109 (3.7%) were
      negative for all these agents. Escherichia coli strains were isolated from all
      submissions tested, but only 11 of them were classified into defined pathotypes.
      Clostridium perfringens type A was detected in 98 submissions (89.9%) and no C.
      perfringens type C was found. Regarding viruses, 47 (43.1%) submissions were
      positive for RVA, 4 (3.7%) for PEDV and none of them for TGEV. Conclusion: In
      conclusion, C. perfringens type A, E. coli and RVA were the main pathogens found
      in faeces of neonatal diarrheic piglets in Spain.

PMID- 29632702
TI  - Knowledge, attitudes and practices of hypertensive patients towards prevention
      and early detection of chronic kidney disease: a cross sectional study from
      Palestine.
AB  - Background: Hypertension is the second most common cause of chronic kidney
      disease (CKD). Therefore, the aims of the study were to assess the knowledge,
      attitudes and practices (KAP) of hypertensive patients towards prevention and
      early detection of CKD, and to determine the clinical and socio-demographic
      factors, which affect the KAP regarding prevention of CKD. Methods: A cross
      sectional study was held using the CKD screening Index to assess the KAP of 374
      hypertensive patients who were selected from multiple primary healthcare centers
      in Nablus, Palestine. The CKD Screening Index is formed of three scales. First,
      the knowledge scale was a dichotomous scale of 30 items, while the attitude scale
      used 5-point Likert-type scale for 18 items and finally the practice scale was
      measured using 4-point Likert-type scale for 12 items. Multiple linear regression
      analysis was used to determine the association between clinical and socio
      demographic factors and practices. Results: In total, 374 hypertensive patients
      participated in the study. The mean age of participants was 59.14 +/- 10.4 years,
      (range 26-85). The median (interquartile range) of the knowledge, attitude, and
      practice scores of hypertensive patients towards prevention and early detection
      of CKD were 20 (16-23), 69 (65-72), and 39 (36-42), respectively. In multiple
      linear regression analysis, patients age < 65 years (p < 0.001) and patients with
      high education level (p = 0.009) were the only factors significantly associated
      with higher knowledge scores. Additionally, patients age < 65 years (p = 0.007),
      patients with high income (p = 0.005), and patients with high knowledge score (p
      < 0.001) were the only factors significantly associated with higher attitude
      scores. Furthermore, regression analysis showed that patients with higher total
      knowledge (p = 0.001) as well as higher total attitudes scores towards CKD
      prevention (p < 0.001), male gender (p = 0.048), and patients with normal body
      mass index (BMI) (p = 0.026) were statistically significantly associated with
      higher practice score towards CKD prevention. Conclusions: Among hypertensive
      patients, higher scores for total knowledge and attitudes toward prevention, male
      sex, and normal BMI were associated with modestly higher scores for prevention
      practices. Finally the findings may encourage healthcare workers to give better
      counseling to improve knowledge.

PMID- 29632703
TI  - Intravitreal dexamethasone implant versus triamcinolone acetonide for macular
      oedema of central retinal vein occlusion: quantifying efficacy and safety.
AB  - Purpose: Among the retinal vascular diseases, burden of retinal vein occlusion is
      most common immediately after diabetic retinopathy. Intravitreal corticosteroids
      are gaining popularity in managing macular edema (ME) of RVO. Our study compares
      efficacy and safety of intravitreal triamcinolone (IVTA) and dexamethasone
      implant (IVD) over 6 months. Methods: This comparative, prospective, randomized
      study on 40 patients of non-ischemic central RVO with significant ME (> 330 MUm)
      of < 3 months duration. Study was done at Army Research Hospital between Sep-2012
      and May-2014 in accordance to Helsinki Declaration. IVD group (n = 20) received
      Ozurdex(r) while IVTA group (n = 20) received triamcinolone-acetonide (4 mg/0.1
      ml), followed up at day-1 and weeks 4, 8, 12, 24. Results: At 6 months, mean
      improvement in best corrected visual acuity and retinal thickness (CMT) in the
      IVD group was 0.43 logmar and 323 MUm and in IVTA group was 0.49 logmar and 322
      MUm respectively. Proportion of patients achieving >= 15 letters was about 40% in
      both groups. IOP rise was significantly higher in IVTA group at 12 and 24 weeks.
      In IVTA group >= 10 mmHg IOP rise was seen in 60% of patients, 41.6% among them
      had > 35 mmHg and 66% needed combination treatment and failed to reach baseline
      line IOP at 6 months. In IVD group, 5 pts had IOP rise with all being < 26 mmHg
      and were easily managed with single agent with IOP reaching baseline by 6th month
      in all pts. Relative risk of IOP rise with IVTA is 2.4 times higher compared to
      IVD. Cataract progression and cataract surgeries were required at significantly
      higher rates in IVTA group. In IVTA group, cataract progression was seen in 35%
      patients, with 71.5% requiring cataract surgery at 6 months. IVD group, 10%
      patients had cataract progression while none required surgery at 6 months.
      Relative risk of cataract progression with IVTA is 3.5 times higher compared to
      IVD. Conclusion: Intravitreal steroids are effective in managing macular edema of
      retinal vein occlusion, while newer formulation of sustained release
      dexamethasone implant is significantly safer than IVTA.

PMID- 29632704
TI  - Effective coverage of primary care services in eight high-mortality countries.
AB  - Introduction: Measurement of effective coverage (quality-corrected coverage) of
      essential health services is critical to monitoring progress towards the
      Sustainable Development Goal for health. We combine facility and household
      surveys from eight low-income and middle-income countries to examine effective
      coverage of maternal and child health services. Methods: We developed indices of
      essential clinical actions for antenatal care, family planning and care for sick
      children from existing guidelines and used data from direct observations of
      clinical visits conducted in Haiti, Kenya, Malawi, Namibia, Rwanda, Senegal,
      Tanzania and Uganda between 2007 and 2015 to measure quality of care delivered.
      We calculated healthcare coverage for each service from nationally representative
      household surveys and combined quality with utilisation estimates at the
      subnational level to quantify effective coverage. Results: Health facility and
      household surveys yielded over 40 000 direct clinical observations and over 100
      000 individual reports of healthcare utilisation. Coverage varied between
      services, with much greater use of any antenatal care than family planning or
      sick-child care, as well as within countries. Quality of care was poor, with few
      regions demonstrating more than 60% average performance of basic clinical
      practices in any service. Effective coverage across all eight countries averaged
      28% for antenatal care, 26% for family planning and 21% for sick-child care.
      Coverage and quality were not strongly correlated at the subnational level;
      effective coverage varied by as much as 20% between regions within a country.
      Conclusion: Effective coverage of three primary care services for women and
      children in eight countries was substantially lower than crude service coverage
      due to major deficiencies in care quality. Better performing regions can serve as
      examples for improvement. Systematic increases in the quality of care delivered
      not just utilisation gains-will be necessary to progress towards truly beneficial
      universal health coverage.

PMID- 29632705
TI  - Integrating Foundational Sciences in a Clinical Context in the Post-Clerkship
      Curriculum.
AB  - Purpose: To design, implement, and launch courses that integrate foundational
      science learning and clinical application in a post-clerkship undergraduate
      medical school curriculum. Method: In Academic Year (AY) 15-16, as part of a
      comprehensive curricular revision, Vanderbilt University School of Medicine
      (VUSM) formally implemented "Integrated Science Courses" (ISCs) that combined
      rigorous training in the foundational sciences with meaningful clinical
      experiences. These courses integrated foundational sciences that could be
      leveraged in the clinical environment, utilized a variety of instructional
      modalities, and included quantitative and qualitative (competency-based
      milestones) student assessments. Each ISC underwent a rigorous quality
      improvement process that required input on foundational science content, student
      experience, and student performance assessment. Results: Eleven ISCs were
      delivered to 173 students in AY15-16, with some students taking more than one
      ISC. Immediately after completing each course, 93% (n=222) of ISC enrollees
      completed a course evaluation. Students (91%; n=201) 'agreed' or 'strongly
      agreed' that foundational science learning informed and enriched the clinical
      experiences. Furthermore, 94% (n=209) of students thought that the clinical
      experiences informed and enriched the foundational science learning. Ninety-four
      percent of the students anticipated using the foundational science knowledge
      acquired in future clinical training and practice. Conclusion: The teaching of
      foundational sciences in the clinical workplace in the post-clerkship medical
      curriculum is challenging and resource-intensive, yet feasible. Additional
      experience with the model will inform the mix of courses as well as the breadth
      and depth of foundational science instruction that is necessary to foster
      scientifically-based clinical reasoning skills in each student.

PMID- 29632706
TI  - Shuffling the deck with CTLA-4 therapy: Deep sequencing of rearranged TCRB genes
      demonstrates T cell repertoire remodeling in cancer patients.
AB  - CTLA-4 inhibition produces durable T cell-driven antitumor responses, but
      understanding which patients achieve a long-term benefit remains unclear. Deep
      sequencing of rearranged T cell receptor beta (TCRbeta) genes can monitor the
      effects of CTLA-4 inhibition and potentially identify patients with long-term
      survival.

PMID- 29632707
TI  - STINGing the Tumor's immune evasion mechanism.
AB  - In order to enhance the STING dependent type I interferon (IFN) response, we
      formulated cyclic dinucleotides (CDN) with cancer vaccines to develop STINGVAX.
      Interestingly, tumors from STINGVAX treated mice demonstrated dramatic PD-L1
      upregulation. When combined with PD-1 blockade, STINGVAX induced regression of
      established tumors that did not respond to PD-1 blockade alone.

PMID- 29632709
TI  - A targeted immunotherapy approach for HER2/neu transformed tumors by coupling an
      engineered effector domain with interferon-gamma.
AB  - Despite substantial clinical progress with targeted therapies, current antibody
      based approaches have limited efficacy at controlling HER2/neu-positive breast
      cancers, especially in the absence of chemotherapies. Previously, we showed that
      the combination of IFNgamma and anti-HER2/neu antibody synergistically reduces
      tumor growth in an in vivo implanted mammary tumor model. Here, we report a
      recombinant approach to produce an anti-HER2/neu scFv and IFNgamma fusion protein
      using an engineered effector domain (EED) scaffold. The new molecule induces in
      vitro apoptosis in an IFNgamma receptor-dependent manner. At a very low dose in
      the in vivo xenografted tumor models, the new EED-IFNgamma fusion protein
      demonstrates superior activity over the anti-HER2/neu antibody and is even active
      on tumors that are resistant to anti-HER2/neu antibody therapy. Examination of
      tumor infiltrated macrophages and lymphocytes reveals that the fusion protein can
      induce changes in tumor microenvironment to support immune reactivity against
      tumors. Our studies have defined a targeted immunotherapy approach for the
      treatment of cancers.

PMID- 29632708
TI  - S100A4 blockage alleviates agonistic anti-CD137 antibody-induced liver pathology
      without disruption of antitumor immunity.
AB  - Liver-related autoimmune toxicities triggered by agonistic anti-CD137 antibodies
      have greatly limited their use in clinical applications. Here, we found that anti
      CD137 monoclonal antibody (mAb) treatment in mice induced the infiltration of a
      large number of S100A4+ macrophages into the liver. Depletion of these cells or
      deficiency of S100A4 decreased inflammatory cytokine profiles and drastically
      reduced the number of liver pathogenic CD8+ T cells. Mechanistically, soluble
      S100A4 directly activated the Akt pathway and specifically prolonged CD8+ T cell
      survival. Interestingly, one S100A4 neutralizing mAb selectively alleviated liver
      abnormalities but did not affect the antitumor immunity induced by anti-CD137 mAb
      therapy. Thus, our study presents a novel molecular link to the liver pathology
      induced by an immune stimulatory antibody and proposes that combinational
      immunotherapies targeting those pathways could potentially elicit optimal
      antitumor immunity with minimal side effects.

PMID- 29632710
TI  - A phase 1 trial extension to assess immunologic efficacy and safety of prime
      boost vaccination with VXM01, an oral T cell vaccine against VEGFR2, in patients
      with advanced pancreatic cancer.
AB  - VXM01 is a first-in-kind orally applied tumor vaccine based on live attenuated
      Salmonella typhi carrying an expression plasmid encoding VEGFR2, an antigen
      expressed on tumor vasculature and a stable and accessible target for anti
      angiogenic intervention. A recent randomized, placebo-controlled, phase I dose
      escalation trial in advanced pancreatic cancer patients demonstrated safety,
      immunogenicity and transient, T-cell response-related anti-angiogenic activity of
      four priming vaccinations applied within one week. We here evaluated whether
      monthly boost vaccinations are safe and can sustain increased frequencies of
      vaccine-specific T cells. Patients with advanced pancreatic cancer were randomly
      assigned at a ratio of 2:1 to priming with VXM01 followed by up to six monthly
      boost vaccinations, or placebo treatment. Vaccinations were applied orally at two
      alternative doses of either 106 colony-forming units (CFU) or 107 CFU, and
      concomitant treatment with standard-of-care gemcitabine during the priming phase,
      and any treatment thereafter, was allowed in the study. Immunomonitoring involved
      interferon-gamma (IFNgamma) ELIspot analysis with long overlapping peptides
      spanning the entire VEGFR2 sequence. A total of 26 patients were treated.
      Treatment-related adverse events preferentially associated with VXM01 were
      decreases in lymphocyte numbers in the blood, increased frequencies of
      neutrophils and diarrhea. Eight out of 16 patients who received at least one
      boosting vaccination responded with pronounced, i.e. at least 3-fold, increase in
      VEGFR2-specific T cell response over baseline levels. In the VXM01 vaccination
      group, VEGFR2-specific T cells peaked preferentially during the boosting phase
      with an average 4-fold increase over baseline levels. In conclusion, prime/boost
      vaccination with VXM01 was safe and immunogenic and increased vaccine specific T
      cell responses compared with placebo treatment.

PMID- 29632711
TI  - HLA ligandome analysis of primary chronic lymphocytic leukemia (CLL) cells under
      lenalidomide treatment confirms the suitability of lenalidomide for combination
      with T-cell-based immunotherapy.
AB  - Recent studies suggest that CLL is an immunogenic disease, which might be
      effectively targeted by antigen-specific T-cell-based immunotherapy. However, CLL
      is associated with a profound immune defect, which might represent a critical
      limitation for mounting clinically effective antitumor immune responses. As
      several studies have demonstrated that lenalidomide can reinforce effector T-cell
      responses in CLL, the combination of T-cell-based immunotherapy with the
      immunomodulatory drug lenalidomide represents a promising approach to overcome
      the immunosuppressive state in CLL. Antigen-specific immunotherapy also requires
      the robust presentation of tumor-associated HLA-presented antigens on target
      cells. We thus performed a longitudinal study of the effect of lenalidomide on
      the HLA ligandome of primary CLL cells in vitro. We showed that lenalidomide
      exposure does not affect absolute HLA class I and II surface expression levels on
      primary CLL cells. Importantly, semi-quantitative mass spectrometric analyses of
      the HLA peptidome of three CLL patient samples found only minor qualitative and
      quantitative effects of lenalidomide on HLA class I- and II-restricted peptide
      presentation. Furthermore, we confirmed stable presentation of previously
      described CLL-associated antigens under lenalidomide treatment. Strikingly, among
      the few HLA ligands showing significant modulation under lenalidomide treatment,
      we identified upregulated IKZF-derived peptides, which may represent a direct
      reflection of the cereblon-mediated effect of lenalidomide on CLL cells. Since we
      could not observe any relevant influence of lenalidomide on the established CLL
      associated antigen targets of anticancer T-cell responses, this study validates
      the suitability of lenalidomide for the combination with antigen-specific T-cell
      based immunotherapies.

PMID- 29632713
TI  - CD47 is a direct target of SNAI1 and ZEB1 and its blockade activates the
      phagocytosis of breast cancer cells undergoing EMT.
AB  - We report that CD47 was upregulated in different EMT-activated human breast
      cancer cells versus epithelial MCF7 cells. Overexpression of SNAI1 or ZEB1 in
      epithelial MCF7 cells activated EMT and upregulated CD47 while siRNA-mediated
      targeting of SNAI1 or ZEB1 in mesenchymal MDA-MB-231 cells reversed EMT and
      strongly decreased CD47. Mechanistically, SNAI1 and ZEB1 upregulated CD47 by
      binding directly to E-boxes in the human CD47 promoter. TCGA and METABRIC data
      sets from breast cancer patients revealed that CD47 correlated with SNAI1 and
      Vimentin. At functional level, different EMT-activated breast cancer cells were
      less efficiently phagocytosed by macrophages vs. MCF7 cells. The phagocytosis of
      EMT-activated cells was rescued by using CD47 blocking antibody or by genetic
      targeting of SNAI1, ZEB1 or CD47. These results provide a rationale for an
      innovative preclinical combination immunotherapy based on PD-1/PD-L1 and CD47
      blockade along with EMT inhibitors in patients with highly aggressive,
      mesenchymal, and metastatic breast cancer.

PMID- 29632712
TI  - Tailoring CD19xCD3-DART exposure enhances T-cells to eradication of B-cell
      neoplasms.
AB  - Many patients with B-cell malignancies can be successfully treated, although
      tumor eradication is rarely achieved. T-cell-directed killing of tumor cells
      using engineered T-cells or bispecific antibodies is a promising approach for the
      treatment of hematologic malignancies. We investigated the efficacy of CD19xCD3
      DART bispecific antibody in a broad panel of human primary B-cell malignancies.
      The CD19xCD3 DART identified 2 distinct subsets of patients, in which the
      neoplastic lymphocytes were eliminated with rapid or slow kinetics. Delayed
      responses were always overcome by a prolonged or repeated DART exposure. Both CD4
      and CD8 effector cytotoxic cells were generated, and DART-mediated killing of
      CD4+ cells into cytotoxic effectors required the presence of CD8+ cells. Serial
      exposures to DART led to the exponential expansion of CD4 + and CD8 + cells and
      to the sequential ablation of neoplastic cells in absence of a PD-L1-mediated
      exhaustion. Lastly, patient-derived neoplastic B-cells (B-Acute Lymphoblast
      Leukemia and Diffuse Large B Cell Lymphoma) could be proficiently eradicated in a
      xenograft mouse model by DART-armed cytokine induced killer (CIK) cells.
      Collectively, patient tailored DART exposures can result in the effective
      elimination of CD19 positive leukemia and B-cell lymphoma and the association of
      bispecific antibodies with unmatched CIK cells represents an effective modality
      for the treatment of CD19 positive leukemia/lymphoma.

PMID- 29632714
TI  - Potentiating tumor immunity using aptamer-targeted RNAi to render CD8+ T cells
      resistant to TGFbeta inhibition.
AB  - TGFbeta secreted by tumor cells and/or tumor infiltrating stromal cells is a key
      mediator of tumor growth and immune suppression at the tumor site. Nonetheless,
      clinical trials in cancer patients targeting the TGFbeta pathway exhibited at
      best a modest therapeutic benefit. A likely reason, a common limitation of many
      cancer drugs, is that the physiologic roles of TGFbeta in tissue homeostasis,
      angiogenesis, and immune regulation precluded the dose escalation necessary to
      achieve a profound clinical response. Murine studies have suggested that
      countering immune suppressive effects of TGFbeta may be sufficient to inhibit
      tumor growth. Here we describe an approach to render vaccine-activated CD8+ T
      cells transiently resistant to TGFbeta inhibition using an siRNA against Smad4 to
      inhibit a key step in the canonical TGFbeta signaling pathway. The siRNA was
      targeted to vaccine activated CD8+ T cells in the mouse by conjugation to a 4-1BB
      binding oligonucleotide (ODN) aptamer ligand (4-1BB-Smad4 conjugate). In vitro
      the 4-1BB-Smad4 conjugate rendered T cells partially resistant to TGFbeta
      inhibition, and treatment of tumor bearing mice with systemically administered 4
      1BB-Smad4 conjugate enhanced vaccine- and irradiation-induced antitumor immunity.
      Limiting the inhibitory effects of TGFbeta to tumor-specific T cells will not
      interfere with its multiple physiologic roles and hence reduce the risk of
      toxicity.

PMID- 29632715
TI  - Biglycan-mediated upregulation of MHC class I expression in HER-2/neu-transformed
      cells.
AB  - The extracellular matrix protein biglycan (BGN) has oncogenic or tumor
      suppressive potential depending on the cellular origin. HER-2/neu overexpression
      in murine fibroblasts and human model systems is inversely correlated with BGN
      expression. Upon its restoration BGNhigh HER-2/neu+ fibroblasts were less
      tumorigenic in immune competent mice when compared to BGNlow/neg HER-2/neu+
      cells, which was associated with enhanced immune cell responses and higher
      frequencies of immune effector cells in tumors and peripheral blood. The
      increased immunogenicity of BGNhigh HER-2/neu+ fibroblasts appears to be due to
      upregulated MHC class I surface antigens and reduced expression levels of
      transforming growth factor (TGF)-beta isoforms and the TGF-beta receptor 1
      suggesting a link between BGN, TGF-beta pathway and HER-2/neu-mediated
      downregulation of MHC class I antigens. Treatment of BGNlow/neg HER-2/neu+ cells
      with recombinant BGN or an inhibitor of TGF-beta enhanced MHC class I surface
      antigens in BGNlow/neg HER-2/neu-overexpressing murine fibroblasts, which was
      mediated by a transcriptional upregulation of major MHC class I antigen
      processing components. Furthermore, BGN expression in HER-2/neu+ cells was
      accompanied by an increased expression of the proteoglycan decorin (DCN). Since
      recombinant DCN also elevated MHC class I surface expression in BGNlow/neg HER
      2/neu+ cells, both proteoglycans might act synergistically. This was in
      accordance with in silico analyses of mRNA data obtained from The Cancer Genome
      Atlas (TCGA) dataset available for breast cancer (BC) patients. Thus, our data
      provide for the first time evidence that proteoglycan signatures are modulated by
      HER-2/neu and linked to MHC class I-mediated immune escape associated with an
      altered TGF-beta pathway.

PMID- 29632716
TI  - Activated human primary NK cells efficiently kill colorectal cancer cells in 3D
      spheroid cultures irrespectively of the level of PD-L1 expression.
AB  - Haploidentical Natural Killer (NK) cells have been shown as an effective and safe
      alternative for the treatment of haematological malignancies with poor prognosis
      for which traditional therapies are ineffective. In contrast to haematological
      cancer cells, that mainly grow as single suspension cells, solid carcinomas are
      characterised by a tridimensional (3D) architecture that provide specific
      surviving advantages and resistance against chemo- and radiotherapy. However,
      little is known about the impact of 3D growth on solid cancer immunotherapy
      especially adoptive NK cell transfer. We have recently developed a protocol to
      activate ex vivo human primary NK cells using B lymphoblastic cell lines, which
      generates NK cells able to overcome chemoresistance in haematological cancer
      cells. Here we have analysed the activity of these allogeneic NK cells against
      colorectal (CRC) human cell lines growing in 3D spheroid culture and correlated
      with the expression of some of the main ligands regulating NK cell activity. Our
      results indicate that activated NK cells efficiently kill colorectal tumour cell
      spheroids in both 2D and 3D cultures. Notably, although 3D CRC cell cultures
      favoured the expression of the inhibitory immune checkpoint PD-L1, it did not
      correlate with increased resistance to NK cells. Finally, we have analysed in
      detail the infiltration of NK cells in 3D spheroids by microscopy and found that
      at low NK cell density, cell death is not observed although NK cells are able to
      infiltrate into the spheroid. In contrast, higher densities promote tumoural cell
      death before infiltration can be detected. These findings show that highly dense
      activated human primary NK cells efficiently kill colorectal carcinoma cells
      growing in 3D cultures independently of PD-L1 expression and suggest that the use
      of allogeneic activated NK cells could be beneficial for the treatment of
      colorectal carcinoma.

PMID- 29632717
TI  - Anti-CD47 treatment enhances anti-tumor T-cell immunity and improves
      immunosuppressive environment in head and neck squamous cell carcinoma.
AB  - Head and neck squamous cell carcinoma (HNSCC) is considered as an
      immunosuppressive disease, with impaired tumor-infiltrating T lymphocytes and
      increased suppressive immune cells. The efficacy of CD47 antibodies in immune
      checkpoint therapy is not clearly understood in HNSCC. In this study, human
      tissue microarrays and immunocompetent transgenic mouse models were used to
      explore the expression of CD47 and the use of CD47 antibodies in HNSCC. We
      identified overexpression of CD47 in HNSCC as compared with the control normal
      human tissue and also in HNSCC mouse models. The expression of CD47 also
      correlated with clinicopathological parameters as well as outcome. Furthermore,
      inhibition of CD47 delayed tumor growth and improved tumor microenvironment by
      stimulating effector T cells and decreasing suppressive immune cells and
      regulating the function of CD11b+ Ly6G+ MDSC. Our data suggest that CD47 blockade
      may be a potential immunotherapeutic target in human HNSCC.

PMID- 29632719
TI  - Combination therapy with PD-1/PD-L1 blockade: An overview of ongoing clinical
      trials.
AB  - Monoclonal antibodies (mAbs) that block the programmed death 1 (PD-1) or
      programmed death-ligand 1 (PD-L1) receptors are the most clinically advanced
      tumor immunotherapies. Given the broad antitumor efficacy and novel mechanism of
      action, numerous combinatorial approaches incorporating PD-1/PD-L1 blockade have
      been suggested; herein we present a comprehensive analysis of these clinical
      trials. We queried clinicaltrials.gov for all PD-1/PD-L1 mAbs administered for
      cancer therapy with an end date of 4/30/2017. A total of 1,218 clinical trials
      met our search criteria. These trials have a planned enrollment of 227,190
      patients, and approximately half (493) were initiated in 2016 alone. Of these
      over 1,200 trials, 916 combine PD-1/PD-L1 blockade with at least one additional
      therapy, ranging from traditional treatment modalities like surgery and
      chemoradiation to newer therapies like small molecule inhibitors and other
      immunotherapies. The staggering proliferation of clinical trials combining PD
      1/PD-L1 blockade with disparate treatments necessitates careful accounting to
      maximize efficiency and highlight areas of unmet needs. We believe our analysis
      provides this data and expect it will facilitate the design of future clinical
      trials in this burgeoning area of oncology research.

PMID- 29632718
TI  - OX40 expression in hepatocellular carcinoma is associated with a distinct immune
      microenvironment, specific mutation signature, and poor prognosis.
AB  - Immunotherapy's effect against hepatocellular carcinoma (HCC) is hampered by
      immunosuppressive mechanisms in the tumor microenvironment. We assessed the
      clinicopathologic and biologic relevance of OX40, a costimulatory molecular
      expressed by regulatory T cells (Tregs), in HCC. We analyzed the
      immunohistochemistry data of 316 patients treated at West China Hospital (WCH)
      and the RNA sequencing data of 370 patients in The Cancer Genome Atlas (TCGA) to
      determine the clinicopathologic significance of OX40 in HCC. We also assessed
      associations between OX40 and multiple immune-related markers. Using the TCGA
      data, we further characterized the transcriptome, immune cell functions, and
      mutation signature related to OX40. We found that OX40 expression was higher in
      HCC than in adjacent liver tissue. In the WCH set, 136 (43%) patients had high
      OX40 expression, whereas in the TCGA set, 247 (67%) patients had high-OX40
      expression as determined by the X-tile program. High-OX40 expression was
      associated with high serum alpha-fetoprotein level, vascular invasion, and
      shorter survival. The prognostic significance of OX40 was validated in additional
      cohorts. OX40 expression was also associated with CD8A, CD68, LAG3, TIM-3, and PD
      1 expression. High-OX40 expression tumors were characterized by upregulated
      cytokines and exhaustion-specific markers. Analysis of the enrichment data of
      immune cell types indicated that OX40 expression was associated with the
      functions of macrophages, plasmacytoid dendritic cells, and co-inhibitory T
      cells. Finally, high-and low-OX40 expressions were associated with mutations in
      AKT/mTOR and Wnt/beta-catenin signaling, respectively. These results indicate
      that high-OX40 expression represents the activation of multiple immunosuppressive
      pathways and provide a rationale for the therapeutic targeting OX40 in HCC
      patients.

PMID- 29632720
TI  - Blockade of Tumor-Expressed PD-1 promotes lung cancer growth.
AB  - Anti-PD-1 immunotherapy is the standard of care for treating many patients with
      non-small cell lung cancer (NSCLC), yet mechanisms of treatment failure are
      emerging. We present a case of NSCLC, who rapidly progressed during a trial
      (NCT02318771) combining palliative radiotherapy and pembrolizumab. Planned tumor
      biopsy demonstrated PD-1 expression by NSCLC cells. We validated this observation
      by detecting PD-1 transcript in lung cancer cells and by co-localizing PD-1 and
      lung cancer-specific markers in resected lung cancer tissues. We further
      investigated the biological role of cancer-intrinsic PD-1 in a mouse lung cancer
      cell line, M109. Knockout or antibody blockade of PD-1 enhanced M109 viability in
      vitro, while PD-1 overexpression and exposure to recombinant PD-L1 diminished
      viability. PD-1 blockade accelerated growth of M109-xenograft tumors with
      increased proliferation and decreased apoptosis in immune-deficient mice. This
      represents a first-time report of NSCLC-intrinsic PD-1 expression and a potential
      mechanism by which PD-1 blockade may promote cancer growth.

PMID- 29632721
TI  - The Toll like receptor 4 ligand cold-inducible RNA-binding protein as vaccination
      platform against cancer.
AB  - Tumor infiltrating lymphocytes have been associated with a better prognostic and
      with higher response rates in patients treated with checkpoint inhibiting
      antibodies, suggesting that strategies promoting tumor inflammation may enhance
      the efficacy of these currently available therapies. Our aim was thus to develop
      a new vaccination platform based on cold-inducible RNA binding protein (CIRP), an
      endogenous TLR4 ligand generated during inflammatory processes, and characterize
      whether it was amenable to combination with checkpoint inhibitors. In vitro, CIRP
      induced dendritic cell activation, migration and enhanced presentation of CIRP
      bound antigens to T-cells. Accordingly, antigen conjugation to CIRP conferred
      immunogenicity, dependent on immunostimulatory and antigen-targeting capacities
      of CIRP. When applied in a therapeutic setting, vaccination led to CD8-dependent
      tumor rejection in several tumor models. Moreover, immunogenicity of this
      vaccination platform was enhanced not only by combination with additional
      adjuvants, but also with antibodies blocking PD-1/PD-L1, CTLA-4 and IL-10,
      immunosuppressive molecules usually present in the tumor environment and also
      induced by the vaccine. Therefore, priming with a CIRP-based vaccine combined
      with immune checkpoint-inhibiting antibodies rejected established B16-OVA tumors.
      Finally, equivalent activation and T-cell stimulatory effects were observed when
      using CIRP in vitro with human cells, suggesting that CIRP-based vaccination
      strategies could be a valuable clinical tool to include in combinatorial
      immunotherapeutic strategies in cancer patients.

PMID- 29632722
TI  - NK cell activation and recovery of NK cell subsets in lymphoma patients after
      obinutuzumab and lenalidomide treatment.
AB  - Obinutuzumab (OBZ) shows stronger antibody-dependent cell cytotoxicity (ADCC)
      compared to rituximab and improved clinical activity for treating certain CD20+
      neoplasia. However, the efficacy of monoclonal antibody (mAb) as a monotherapy is
      limited. Natural Killer (NK) cells are mediators of ADCC. Hematological cancer
      patients possess antitumor NK cells that are unable to control disease, possibly
      because they are dysfunctional. The immunomodulatory drug lenalidomide (LEN)
      could be a treatment to restore exhausted NK cell cytotoxic functions. The
      clinical trial GALEN is a Phase Ib/II study of OBZ combined with LEN for the
      treatment of relapsed/refractory follicular and aggressive (DLBCL and MCL) B-cell
      Lymphoma. During treatment, we analyzed specific aspects of NK cell biology.
      Treatment reversed the immature NK phenotype of patients and increased expression
      of NK activating receptors. Inhibitory receptors were either unchanged or
      decreased. There was a strong NK response at the end of the 1st cycle: NK number
      and intracellular granzyme B (GrzB) expression decreased, degranulation increased
      and NK responded better to allogeneic target challenge. Moreover, the interaction
      of NK cells with B cell targets, measured by trogocytosis, decreased during
      treatment. At the end of treatment, when target cells had been wiped out, the
      proportion of reactive NK cells (CD69+, CD45RARO+, CD107a+, CD19+) strongly
      decreased. Because all patients received LEN and OBZ, it was uncertain which drug
      was responsible of our observations, or even if a combination of both products
      was necessary for the described effects on this lymphocyte lineage.

PMID- 29632723
TI  - Enhanced protection of C57 BL/6 vs Balb/c mice to melanoma liver metastasis is
      mediated by NK cells.
AB  - The B16F10 murine melanoma cell line displays a low expression of MHC class I
      molecules favoring immune evasion and metastases in immunocompetent C57 BL/6 wild
      type mice. Here, we generated metastases to the liver, an organ that is skewed
      towards immune tolerance, by intrasplenic injection of B16F10 cells in syngeneic
      C57 BL/6 compared to allogeneic Balb/c mice. Surprisingly, Balb/c mice, which
      usually display a pronounced M2 macrophage and Th2 T cell polarization, were ~3
      times more susceptible to metastasis than C57 BL/6 mice, despite a much higher M1
      and Th1 T cell immune response. The anti-metastatic advantage of C57 BL/6 mice
      could be attributed to a more potent NK-cell mediated cytotoxicity against B16F10
      cells. Our findings highlight the role of NK cells in innate anti-tumor immunity
      in the context of the liver - particularly against highly aggressive MHC I
      deficient cancer cells. Moreover, the B16F10 model of melanoma liver metastasis
      is suited for developing novel therapies targeting innate NK cell related
      immunity in liver metastases and liver cancer.

PMID- 29632724
TI  - Improved migration of tumor ascites lymphocytes to ovarian cancer
      microenvironment by CXCR2 transduction.
AB  - Chemokines are essential mediators of cellular trafficking, interactions and
      tumor development. Though adoptive cell therapy (ACT) has been a tremendous
      success in the treatment of metastatic melanoma (MM), a major obstacle for
      successful ACT, is limited homing of effector T cells to immune suppressive tumor
      sites. We hypothesized that equipping T cells with chemokine receptors matching
      the chemokines of the tumor microenvironment, could improve tumor homing of T
      cells. T cells from malignant ascites (n = 13); blood from ovarian cancer (OC)
      patients (n = 14); and healthy donors (n = 13) were analyzed by flow cytometry.
      We found that FoxP3+ regulatory T cells accumulation in patients with OC
      associates with CCR4 expression. We characterized a chemokine profile of ascites
      chemokines, and expression of corresponding receptors on circulating T cells and
      tumor ascites lymphocytes (TALs). CCL22, CXCL9, CXCL10 and CXCL12 associated with
      enrichment of CCR4+, CCR5+, CXCR3+ and CXCR4+ T cells in ascites. Circulating T
      cells and TALs however did not express CXCR2, identifying CXCR2 as candidate for
      chemokine receptor transduction. TALs readily expressed IFNgamma and TNFalpha
      upon stimulation despite the frequency decreasing with in vitro expansion.
      Lentiviral transduction of TALs (n = 4) with chemokine receptor CXCR2
      significantly increased transwell migration of TALs towards rhIL8 and autologous
      ascites. The majority of expanded and transduced TALs were of a T effector memory
      subtype. This proof of concept study shows that chemokine receptor engineering
      with CXCR2 is feasible and improves homing of transduced TALs towards the OC
      microenvironment.

PMID- 29632725
TI  - SALL4 oncogene is an immunogenic antigen presented in various HLA-DR contexts.
AB  - Purpose: To investigate the immunoprevalence of SALL4-derived peptides in healthy
      volunteers and cancer patients. Experimental Design: A multistep approach
      including prediction algorithms was used to design in silico SALL4-derived
      peptides theoretically able to bind on common HLA-DR and HLA-A/B molecules. The
      presence of T-cell responses after a long term T-cell assay (28 days) against
      SALL4 was monitored in 14 healthy donors and the presence of T-cell responses
      after a short term T-cell assay (10 days) was monitored in 67 cancer patients
      using IFN-gamma ELISPOT assay. A T-cell clone specific for the immunoprevalent
      A18 K-derived peptide was isolated, characterized and used as a tool to
      characterize the natural processing of A18 K. Results: A SALL4 specific T-cell
      repertoire was present in healthy donors (8/14) and cancer patients (29/67) after
      short term T-cell assay. We further identified two immunoprevalant SALL4-derived
      peptides, R18 A and A18 K, which bind MHC-class II. In parallel, an A18 K
      specific Th1 clone recognized monocyte derived Dendritic Cell (moDC) loaded with
      SALL4 containing cell lysate. The level of IFN-gamma secreted by specific T-cell
      clone was greater in presence of moDC loaded with SALL4 containing cell lysate
      (49.23 +/- 14.02%) than with moDC alone (18.03 +/- 3.072%) (p = 0.0477)
      Conclusion: These results show for the first time immunogenicity of SALL4
      oncogenic protein-derived peptides, especially A18 K and R18 A peptides and make
      them potential targets for personalized medicine. Thus, SALL4 possess major
      characteristics of a tumor antigen.

PMID- 29632726
TI  - Modulation of CD8+ memory stem T cell activity and glycogen synthase kinase 3beta
      inhibition enhances anti-tumoral immunity in gastric cancer.
AB  - The potential contributions of CD8+ memory stem T cells to anti-tumor immunity
      and immunotherapy responses in gastric cancer has not been demonstrated. We found
      that CD8+ memory stem T cell frequencies were increased in the peripheral blood
      of gastric cancer patients compared to healthy donors and declined in frequency
      with disease progression. Despite minimal in vitro cytotoxic activity, the
      adoptive transfer of CD8+ memory stem T cells into Rag1-/- tumor bearing mice
      enhanced tumor regression compared to CD8+ central or effector memory T cell
      counterparts. This effect was associated with an increase in splenic, draining
      lymph node and tumor infiltrating CD8+ T cell numbers and the development of an
      altered CD8+ T cell phenotype not seen during homeostasis. GSK-3beta inhibition
      is known to promote memory stem T cell accumulation by arresting effector T cell
      differentiation in vivo. Surprisingly however, GSK-3beta inhibition conversely
      increased the cytotoxic capacity of CD8+ memory stem T cells in vitro, and this
      was associated with the induction of effector T cell-associated effector proteins
      including FasL. Finally, FasL neutralization following GSK-3beta inhibition
      directly attenuated the anti-tumoral capacity of CD8+ memory stem T cells both in
      vitro and in vivo. Altogether, our findings identify the therapeutic potential of
      modulating CD8+ memory stem T cells for improved anti-tumoral responses against
      gastric cancer.

PMID- 29632727
TI  - Survival gain in glioblastoma patients treated with dendritic cell immunotherapy
      is associated with increased NK but not CD8+ T cell activation in the presence of
      adjuvant temozolomide.
AB  - In a two-stage phase II study, 24 patients with first diagnosis of glioblastoma
      (GBM) were treated with dendritic cell (DC) immunotherapy associated to standard
      radiochemotherapy with temozolomide (TMZ) followed by adjuvant TMZ. Three
      intradermal injections of mature DC loaded with autologous GBM lysate were
      administered before adjuvant TMZ, while 4 injections were performed during
      adjuvant TMZ. According to a two-stage Simon design, to proceed to the second
      stage progression-free survival (PFS) 12 months after surgery was expected in at
      least 8 cases enrolled in the first stage. Evidence of immune response and
      interaction with chemotherapy were investigated. After a median follow up of 17.4
      months, 9 patients reached PFS12. In these patients (responders, 37.5%), DC
      vaccination induced a significant, persistent activation of NK cells, whose
      increased response was significantly associated with prolonged survival. CD8+ T
      cells underwent rapid expansion and priming but, after the first administration
      of adjuvant TMZ, failed to generate a memory status. Resistance to TMZ was
      associated with robust expression of the multidrug resistance protein ABCC3 in NK
      but not CD8+ T cells. The negative effect of TMZ on the formation of T cell
      associated antitumor memory deserves consideration in future clinical trials
      including immunotherapy.

PMID- 29632728
TI  - Glioblastoma stem cell-derived exosomes induce M2 macrophages and PD-L1
      expression on human monocytes.
AB  - Exosomes can mediate a dynamic method of communication between malignancies,
      including those sequestered in the central nervous system and the immune system.
      We sought to determine whether exosomes from glioblastoma (GBM)-derived stem
      cells (GSCs) can induce immunosuppression. We report that GSC-derived exosomes
      (GDEs) have a predilection for monocytes, the precursor to macrophages. The GDEs
      traverse the monocyte cytoplasm, cause a reorganization of the actin
      cytoskeleton, and skew monocytes toward the immune suppresive M2 phenotype,
      including programmed death-ligand 1 (PD-L1) expression. Mass spectrometry
      analysis demonstrated that the GDEs contain a variety of components, including
      members of the signal transducer and activator of transcription 3 (STAT3) pathway
      that functionally mediate this immune suppressive switch. Western blot analysis
      revealed that upregulation of PD-L1 in GSC exosome-treated monocytes and GBM
      patient-infiltrating CD14+ cells predominantly correlates with increased
      phosphorylation of STAT3, and in some cases, with phosphorylated p70S6 kinase and
      Erk1/2. Cumulatively, these data indicate that GDEs are secreted GBM-released
      factors that are potent modulators of the GBM-associated immunosuppressive
      microenvironment.

PMID- 29632729
TI  - Repolarizing heterogeneous leukemia-associated macrophages with more M1
      characteristics eliminates their pro-leukemic effects.
AB  - Macrophages exhibit phenotypic heterogeneity under both physiological and
      pathological conditions. Applications targeting M2-like tumor-associated
      macrophages (TAMs) improve outcome in solid tumors. Considerable differences are
      detected between leukemia-associated macrophages (LAMs) and TAMs. However,
      application to induce M1 characteristics in heterogeneous LAMs has not been
      established. Here we analyzed clinical relevance of macrophage phenotypes in
      human acute myeloid leukemia (AML), studied phenotypic evolution of bone marrow
      (BM) and spleen (SP) LAMs in mouse AML and T cell acute lymphoblastic leukemia (T
      ALL) models, explored mechanism leading to different LAM phenotypes and tried to
      eliminate pro-leukemic effects by inducing M1 characteristics. The results showed
      that more M2-like LAMs but not total LAMs correlated with worse prognosis in AML
      patients. Heterogeneity of LAM activation in tissue-specific leukemic
      microenvironments was observed in both AML and ALL models, i.e. SP LAMs evolved
      with more M2 characteristics while BM LAMs with more M1 characteristics.
      Furthermore, IRF7 contributed to M1 characteristics through the activation of
      SAPK/JNK pathway. Moreover, targeting IRF7-SAPK/JNK pathway to induce M1
      characteristics in LAMs contributed to prolonged survival in leukemia mice. Our
      study provides the potential target for macrophage based immuno-therapy strategy
      against leukemia.

PMID- 29632730
TI  - Evaluation of programmed cell death protein 1 (PD-1) expression as a prognostic
      biomarker in patients with clear cell renal cell carcinoma.
AB  - Programmed cell death protein 1 (PD-1) immune checkpoint inhibitors have shown
      activity in patients with advanced renal cell carcinoma (RCC). However, the role
      of PD-1 expression in tumor-infiltrating lymphocytes (TILs) as a biomarker for
      poor outcome is not clear. In this study, we evaluated the prognostic value of
      TIL PD-1 expression in patients with clear cell RCC (ccRCC). 82 patients who
      underwent nephrectomy for localized or metastatic ccRCC and followed up for at
      least four years were searched from our database and retrospectively enrolled.
      Their fixed primary tumor specimens were stained with anti-PD-1 (NAT105). The
      specimens were classified as negative or positive for PD-1 expression, and the
      positive specimens were further scored in 10% increments. 37 (45.12%) patients
      were negative (<1% stained), 26 (31.71%) patients were low (<10 and 10%), and 19
      (23.17%) patients were high (20-50%) for PD-1 expression. The prognostic value of
      TIL PD-1 expression was evaluated by univariate Cox proportional hazards
      regression on overall and recurrence-free survivals. Higher TIL PD-1 expression
      was not associated with increased risk of death (P = 0.336) or with increased
      risk of recurrence (P = 0.572). Higher primary tumor stage was associated with
      increased risk of recurrence (P = 0.003), and higher Fuhrman nuclear grade was
      associated with increased risk of death (P <0.001) and with increased risk of
      recurrence (P <0.001). Our study shows that TIL PD-1 expression by
      immunohistochemistry (IHC) does not correlate with poor clinical outcome in
      patients with ccRCC and is inferior to established prognosticating tools.

PMID- 29632731
TI  - A novel MDSC-induced PD-1-PD-L1+ B-cell subset in breast tumor microenvironment
      possesses immuno-suppressive properties.
AB  - Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of myeloid
      cells that suppress T-cell activity in a tumor microenvironment. However, the
      suppressive function of MDSCs on B cells and its underlying mechanism remain
      unclear. Here, we show that in 4T1 breast cancer mice, a significantly increased
      number of MDSCs, in parallel with splenic B cells, are accumulated when compared
      to normal mice. In the presence of MDSCs, the surface molecules of B cells are
      remolded, with checkpoint-related molecules such as PD-1 and PD-L1 changing
      prominently. MDSCs also emerge as vital regulators in B-cell immune functions
      such as proliferation, apoptosis and the abilities to secrete antibodies and
      cytokines. Our study further identifies that MDSCs can transform normal B cells
      to a subtype of immuno- regulatory B cells (Bregs) which inhibit T-cell response.
      Furthermore, we identified a novel kind of Bregs with a specific phenotype PD-1
      PD-L1+CD19+, which exert the greatest suppressive effects on T cells in
      comparison with the previously reported Bregs characterized as CD1d+CD5+CD19+,
      CD5+CD19+ and Interleukin (IL)-10-secreting B cells. Our results highlight that
      MDSCs regulate B-cell response and may serve as a therapeutic approach in anti
      tumor treatment. Investigation of this new Breg subtype extends our understanding
      of regulation of T-cell response and sheds new light on anti-tumor immunity and
      immune therapy.

PMID- 29632732
TI  - The immunocytokine L19-IL2: An interplay between radiotherapy and long-lasting
      systemic anti-tumour immune responses.
AB  - Recently, we have shown that the administration of the tumour-targeted antibody
      based immunocytokine L19-IL2 after radiotherapy (RT) resulted in synergistic anti
      tumour effect. Here we show that RT and L19-IL2 can activate a curative abscopal
      effect, with a long-lasting immunological memory. Ionizing radiation (single dose
      of 15Gy, 5 * 2Gy or 5 * 5Gy) was delivered to primary C51 colon tumour-bearing
      immunocompetent mice in combination with L19-IL2 and response of secondary non
      irradiated C51 or CT26 colon tumours was evaluated. 15Gy + L19-IL2 triggered a
      curative (20%) abscopal effect, which was T cell dependent. Moreover, 10Gy + L19
      IL2 treated and cured mice were re-injected after 150 days with C51 tumour cells
      and tumour uptake was assessed. Age-matched controls (matrigel injected mice
      treated with 10Gy + L19-IL2, mice cured after treatment with surgery + L19-IL2
      and mice cured after high dose RT 40Gy + vehicle) were included. Several
      immunological parameters in blood, tumours, lymph nodes and spleens were
      investigated. Treatment with 10Gy + L19-IL2 resulted in long-lasting
      immunological memory, associated with CD44+CD127+ expression on circulating T
      cells. This combination treatment can induce long-lasting curative abscopal
      responses, and therefore it has also great potential for treatment of metastatic
      disease. Preclinical findings have led to the initiation of a phase I clinical
      trial (NCT02086721) in our institute investigating stereotactic ablative
      radiotherapy with L19-IL2 in patients with oligometastatic solid tumours.

PMID- 29632733
TI  - Interleukin 7-expressing fibroblasts promote breast cancer growth through
      sustenance of tumor cell stemness.
AB  - The tumor microenvironment harbors cancer-associated fibroblasts that function as
      major modulators of cancer progression. Here, we assessed to which extent
      distinct cancer-associated fibroblast subsets impact mammary carcinoma growth and
      cancer cell stemness in an orthotopic murine model. We found that fibroblasts
      expressing the Cre recombinase under the control of the interleukin 7 promoter
      occupied mainly the tumor margin where they physically interacted with tumor
      cells. Intratumoral ablation of interleukin 7-expressing fibroblasts impaired
      breast tumor growth and reduced the clonogenic potential of cancer cells.
      Moreover, cDNA expression profiling revealed a distinct oncogenic signature of
      interleukin 7-producing fibroblasts. In particular, Cxcl12 expression was
      strongly enhanced in interleukin 7-producing fibroblasts and cell type-specific
      genetic ablation and systemic pharmacological inhibition revealed that the
      CXCL12/CXCR4 axis impacts breast tumor cell stemness. Elevated expression of
      CXCL12 and other stem cell factors in primary human breast cancer-associated
      fibroblasts indicates that certain fibroblast populations support tumor cell
      stemness and thereby promote breast cancer growth.

PMID- 29632734
TI  - Bladder cancer-associated cancer-testis antigen-derived long peptides
      encompassing both CTL and promiscuous HLA class II-restricted Th cell epitopes
      induced CD4+ T cells expressing converged T-cell receptor genes in vitro.
AB  - DEP domain containing 1 (DEPDC1) and M-phase phosphoprotein 1 (MPHOSPH1) are
      human cancer testis antigens that are frequently overexpressed in urinary bladder
      cancer. In a phase I/II clinical trial, a DEPDC1- and MPHOSPH1-derived short
      peptide vaccine demonstrated promising efficacy in preventing bladder cancer
      recurrence. Here, we aimed to identify long peptides (LPs) derived from DEPDC1
      and MPHOSPH1 that induced both T-helper (Th) cells and tumor-reactive cytotoxic T
      lymphocytes (CTLs). Stimulation of peripheral blood mononuclear cells (PBMCs)
      from healthy donors with the synthetic DEPDC1- and MPHOSPH1-LPs predicted to bind
      to promiscuous human leukocyte antigen (HLA) class II molecules by a computer
      algorithm induced specific CD4+ T cells as revealed by interferon-gamma enzyme
      linked immunospot assays. Three of six LPs encompassed HLA-A2- or -A24-restricted
      CTL epitopes or both, and all six LPs stimulated DEPDC1- or MPHOSPH1-specific Th
      cells restricted by promiscuous and frequently observed HLA class II molecules in
      the Japanese population. Some LPs are naturally processed from the proteins in
      DCs, and the capacity of these LPs to cross-prime CTLs was confirmed in vivo
      using HLA-A2 or -A24 transgenic mice. The LP-specific and HLA class II-restricted
      T-cell responses were also observed in PBMCs from patients with bladder cancer.
      Repeated stimulation of PBMCs with DEPDC1-LPs and MPHOSPH1-LPs yielded clonal Th
      cells expressing specific T-cell receptor (TCR)-alpha and beta genes. These
      DEPDC1- or MPHOSPH1-derived LPs may have applications in immunotherapy in
      patients with bladder cancer, and the TCR genes identified may be useful for
      monitoring of Th cells specific to LPs in vivo.

PMID- 29632735
TI  - Dynamic changes of the normal B lymphocyte repertoire in CLL in response to
      ibrutinib or FCR chemo-immunotherapy.
AB  - Using next-generation immunoglobulin (IGH) sequencing and flow cytometry, we
      characterized the composition, diversity and dynamics of non-malignant B cells in
      patients undergoing treatment with the Bruton tyrosine kinase (BTK) inhibitor
      ibrutinib or chemo-immunotherapy with fludarabine, cyclophosphamide, and
      rituximab (FCR). During ibrutinib therapy, non-malignant B cell numbers declined,
      but patients maintained stable IGH diversity and constant fractions of IGH
      mutated B cells. This indicates partial preservation of antigen-experienced B
      cells during ibrutinib therapy, but impaired replenishment of the normal B cell
      pool with naive B cells. In contrast, after FCR we noted a recovery of normal B
      cells with a marked predominance of B cells with unmutated IGH. This pattern is
      compatible with a deletion of pre-existing antigen-experienced B cells followed
      by repertoire renewal with antigen-naive B cells. These opposite patterns in B
      cell dynamics may result in different responses towards neoantigens versus recall
      antigens, which need to be further defined.

PMID- 29632736
TI  - Safety and activity of PD-1 blockade-activated DC-CIK cells in patients with
      advanced solid tumors.
AB  - Cytokine-induced killer (CIK) cells that are stimulated using mature dendritic
      cells (DCs), referred to as (DC-CIK cells) exhibit superior anti-tumor potency.
      Anti-programmed death-1 (PD-1) antibodies reinvigorate T cell-mediated antitumor
      immunity. This phase I study aimed to assess the safety and clinical activity of
      immunotherapy with PD-1 blockade (pembrolizumab)-activated autologous DC-CIK
      cells in patients with advanced solid tumors. Patients with selected types of
      advanced solid tumors received a single intravenous infusion of activated
      autologous DC-CIK cells weekly for the first month and every 2 weeks thereafter.
      The primary end points were safety and adverse event (AE) profiles. Antitumor
      responses, overall survival (OS), progression-free survival (PFS) and cytolytic
      activity were secondary end points. Treatment-related AEs occurred in 20/31
      patients. Grade 3 or 4 toxicities, including fever and chills, were observed in
      two patients. All treatment-related AEs were reversible or controllable. The
      cytotoxicity of DC-CIK cells induced up-regulation of PD-L1 expression on
      autologous tumor cells. When activated using pembrolizumab ex vivo, DC-CIK cells
      exerted superior antitumor properties and elevated IFN-gamma secretion. Objective
      responses (complete or partial responses) were observed in 7 of the
      31patients.These responses were durable, with 6 of 7 responses lasting more than
      5 months. The overall disease control rate in the patients was 64.5%. At the time
      of this report, the median OS and PFS were 270 and 162 days, respectively. In
      conclusions, treatment with pembrolizumab-activated autologous DC-CIK cells was
      safe and exerted encouraging antitumor activity in advanced solid tumors. A
      larger phase II trial is warranted.

PMID- 29632737
TI  - Anti-Melanoma immunity and local regression of cutaneous metastases in melanoma
      patients treated with monobenzone and imiquimod; a phase 2 a trial.
AB  - Vitiligo development in melanoma patients during immunotherapy is a favorable
      prognostic sign and indicates breakage of tolerance against melanocytic/melanoma
      antigens. We investigated a novel immunotherapeutic approach of the skin
      depigmenting compound monobenzone synergizing with imiquimod in inducing
      antimelanoma immunity and melanoma regression. Stage III-IV melanoma patients
      with non-resectable cutaneous melanoma metastases were treated with monobenzone
      and imiquimod (MI) therapy applied locally to cutaneous metastases and adjacent
      skin during 12 weeks, or longer. Twenty-one of 25 enrolled patients were
      evaluable for clinical assessment at 12 weeks. MI therapy was well-tolerated.
      Partial regression of cutaneous metastases was observed in 8 patients and stable
      disease in 1 patient, reaching the statistical endpoint of treatment efficacy.
      Continued treatment induced clinical response in 11 patients, including complete
      responses in three patients. Seven patients developed vitiligo-like
      depigmentation on areas of skin that were not treated with MI therapy, indicating
      a systemic effect of MI therapy. Melanoma-specific antibody responses were
      induced in 7 of 17 patients tested and melanoma-specific CD8+T-cell responses in
      11 of 15 patients tested. These systemic immune responses were significantly
      increased during therapy as compared to baseline in responding patients. This
      study shows that MI therapy induces local and systemic anti-melanoma immunity and
      local regression of cutaneous metastases in 38% of patients, or 52% during
      prolonged therapy. This study provides proof-of-concept of MI therapy, a low
      cost, broadly applicable and well-tolerated treatment for cutaneous melanoma
      metastases, attractive for further clinical investigation.

PMID- 29632738
TI  - A blood dendritic cell vaccine for acute myeloid leukemia expands anti-tumor T
      cell responses at remission.
AB  - Only modest advances in AML therapy have occurred in the past decade and relapse
      due to residual disease remains the major challenge. The potential of the immune
      system to address this is evident in the success of allogeneic transplantation,
      however this leads to considerable morbidity. Dendritic cell (DC) vaccination can
      generate leukemia-specific autologous immunity with little toxicity. Promising
      results have been achieved with vaccines developed in vitro from purified
      monocytes (Mo-DC). We now demonstrate that blood DC (BDC) have superior function
      to Mo-DC. Whilst BDC are reduced at diagnosis in AML, they recover following
      chemotherapy and allogeneic transplantation, can be purified using CMRF-56
      antibody technology, and can stimulate functional T cell responses. While most
      AML patients in remission had a relatively normal T cell landscape, those who had
      received fludarabine as salvage therapy have persistent T cell abnormalities
      including reduced number, altered subset distribution, failure to expand, and
      increased activation-induced cell death. Furthermore, PD-1 and TIM-3 are
      increased on CD4T cells in AML patients in remission and their blockade enhances
      the expansion of leukemia-specific T cells. This confirms the feasibility of a
      BDC vaccine to consolidate remission in AML and suggests it should be tested in
      conjunction with checkpoint blockade.

PMID- 29632739
TI  - Interaction of a dinoflagellate neurotoxin with voltage-activated ion channels in
      a marine diatom.
AB  - Background: The potent neurotoxins produced by the harmful algal bloom species
      Karenia brevis are activators of sodium voltage-gated channels (VGC) in animals,
      resulting in altered channel kinetics and membrane hyperexcitability. Recent
      biophysical and genomic evidence supports widespread presence of homologous
      sodium (Na+) and calcium (Ca2+) permeable VGCs in unicellular algae, including
      marine phytoplankton. We therefore hypothesized that VGCs of these phytoplankton
      may be an allelopathic target for waterborne neurotoxins produced by K. brevis
      blooms that could lead to ion channel dysfunction and disruption of signaling in
      a similar manner to animal Na+ VGCs. Methods: We examined the interaction of
      brevetoxin-3 (PbTx-3), a K. brevis neurotoxin, with the Na+/Ca2+ VGC of the non
      toxic diatom Odontella sinensis using electrophysiology. Single electrode current
      and voltage- clamp recordings from O. sinensis in the presence of PbTx-3 were
      used to examine the toxin's effect on voltage gated Na+/Ca2+ currents. In silico
      analysis was used to identify the putative PbTx binding site in the diatoms. We
      identified Na+/Ca2+ VCG homologs from the transcriptomes and genomes of 12
      diatoms, including three transcripts from O. sinensis and aligned them with site
      5 of Na+ VGCs, previously identified as the PbTx binding site in animals.
      Results: Up to 1 uM PbTx had no effect on diatom resting membrane potential or
      membrane excitability. The kinetics of fast inward Na+/Ca2+ currents that
      underlie diatom action potentials were also unaffected. However, the peak inward
      current was inhibited by 33%, delayed outward current was inhibited by 25%, and
      reversal potential of the currents shifted positive, indicating a change in
      permeability of the underlying channels. Sequence analysis showed a lack of
      conservation of the PbTx binding site in diatom VGC homologs, many of which share
      molecular features more similar to single-domain bacterial Na+/Ca2+ VGCs than the
      4-domain eukaryote channels. Discussion: Although membrane excitability and the
      kinetics of action potential currents were unaffected, the permeation of the
      channels underlying the diatom action potential was significantly altered in the
      presence of PbTx-3. However, at environmentally relevant concentrations the
      effects of PbTx- on diatom voltage activated currents and interference of cell
      signaling through this pathway may be limited. The relative insensitivity of
      phytoplankton VGCs may be due to divergence of site-5 (the putative PbTx binding
      site), and in some cases, such as O. sinensis, resistance to toxin effects may be
      because of evolutionary loss of the 4-domain eukaryote channel, while retaining a
      single domain bacterial-like VGC that can substitute in the generation of fast
      action potentials.

PMID- 29632740
TI  - Reference gene selection for qRT-PCR assays in Stellera chamaejasme subjected to
      abiotic stresses and hormone treatments based on transcriptome datasets.
AB  - Background: Stellera chamaejasme Linn, an important poisonous plant of the China
      grassland, is toxic to humans and livestock. The rapid expansion of S.
      chamaejasme has greatly damaged the grassland ecology and, consequently,
      seriously endangered the development of animal husbandry. To draft efficient
      prevention and control measures, it has become more urgent to carry out research
      on its adaptive and expansion mechanisms in different unfavorable habitats at the
      genetic level. Quantitative real-time polymerase chain reaction (qRT-PCR) is a
      widely used technique for studying gene expression at the transcript level;
      however, qRT-PCR requires reference genes (RGs) as endogenous controls for data
      normalization and only through appropriate RG selection and qRT-PCR can we
      guarantee the reliability and robustness of expression studies and RNA-seq data
      analysis. Unfortunately, little research on the selection of RGs for gene
      expression data normalization in S. chamaejasme has been reported. Method: In
      this study, 10 candidate RGs namely, 18S, 60S, CYP, GAPCP1, GAPDH2, EF1B, MDH,
      SAND, TUA1, and TUA6, were singled out from the transcriptome database of S.
      chamaejasme, and their expression stability under three abiotic stresses
      (drought, cold, and salt) and three hormone treatments (abscisic acid, ABA;
      gibberellin, GA; ethephon, ETH) were estimated with the programs geNorm,
      NormFinder, and BestKeeper. Result: Our results showed that GAPCP1 and EF1B were
      the best combination for the three abiotic stresses, whereas TUA6 and SAND, TUA1
      and CYP, GAPDH2 and 60S were the best choices for ABA, GA, and ETH treatment,
      respectively. Moreover, GAPCP1 and 60S were assessed to be the best combination
      for all samples, and 18S was the least stable RG for use as an internal control
      in all of the experimental subsets. The expression patterns of two target genes
      (P5CS2 and GI) further verified that the RGs that we selected were suitable for
      gene expression normalization. Discussion: This work is the first attempt to
      comprehensively estimate the stability of RGs in S. chamaejasme. Our results
      provide suitable RGs for high-precision normalization in qRT-PCR analysis,
      thereby making it more convenient to analyze gene expression under these
      experimental conditions.

PMID- 29632741
TI  - Electrophysiological evidence for temporal dynamics associated with attentional
      processing in the zoom lens paradigm.
AB  - Background: Visuospatial processing requires wide distribution or narrow focusing
      of attention to certain regions in space. This mechanism is described by the zoom
      lens model and predicts an inverse correlation between the efficiency of
      processing and the size of the attentional scope. Little is known, however, about
      the exact timing of the effects of attentional scaling on visual searching and
      whether or not additional processing phases are involved in this process. Method:
      Electroencephalographic recordings were made while participants performed a
      visual search task under different attentional scaling conditions. Two concentric
      circles of different sizes, presented to the participants at the center of a
      screen modulated the attentional scopes, and search arrays were distributed in
      the space areas indicated by these concentric circles. To ensure consistent
      eccentricity of the search arrays across different conditions, we limited our
      studies to the neural responses evoked by the search arrays distributed in the
      overlapping region of different attentional scopes. Results: Consistent with the
      prediction of the zoom lens model, our behavioral data showed that reaction times
      for target discrimination of search arrays decreased and the associated error
      rates also significantly decreased, with narrowing the attentional scope. Results
      of the event-related potential analysis showed that the target-elicited amplitude
      of lateral occipital N1, rather than posterior P1, which reflects the earliest
      visuospatial attentional processing, was sensitive to changes in the scaling of
      visuospatial attention, indicating that the modulation of the effect of changes
      in the spatial scale of attention on visual processing occurred after the delay
      period of P1. The N1 generator exhibited higher activity as the attentional scope
      narrowed, reflecting more intensive processing resources within the attentional
      focus. In contrast to N1, the amplitude of N2pc increased with the expansion of
      the attentional focus, suggesting that observers might further redistribute
      attentional resources according to the increased task difficulty. Conclusion:
      These findings provide electrophysiological evidence that the neural activity of
      the N1 generator is the earliest marker of the zoom lens effect of visual spatial
      attention. Furthermore, evidence from N2pc shows that there is also a
      redistribution of attentional resources after the action of the zoom lens
      mechanism, which allows for better perform of the search task in the context of
      low attentional resolution. On the basis of the timing of P1, N1, and N2pc, our
      findings provide compelling evidence that visuospatial attention processing in
      the zoom lens paradigm involves multi-stage dynamic processing.

PMID- 29632742
TI  - Serpin functions in host-pathogen interactions.
AB  - Serpins are a broadly distributed superfamily of protease inhibitors that are
      present in all kingdoms of life. The acronym, serpin, is derived from their
      function as potent serine proteases inhibitors. Early studies of serpins focused
      on their functions in haemostasis since modulating serine proteases activities
      are essential for coagulation. Additional research has revealed that serpins
      function in infection and inflammation, by modulating serine and cysteine
      proteases activities. The aim of this review is to summarize the accumulating
      findings and current understanding of the functions of serpins in host-pathogen
      interactions, serving as host defense proteins as well as pathogenic factors. We
      also discuss the potential crosstalk between host and pathogen serpins. We
      anticipate that future research will elucidate the therapeutic value of this
      novel target.

PMID- 29632743
TI  - No tears in heaven: did the media create the pseudo-phenomenon "altitude-adjusted
      lachrymosity syndrome (AALS)"?
AB  - Objective: In the media, numerous public figures have reported involuntary
      emotional outbursts arising from watching films on planes, resembling
      neurological phenomena such as pseudobulbar affect. Putative risk factors put
      forward include altitude, mild hypoxia, or alcohol. Our objective was to
      determine whether watching a film on an airplane is really more likely to induce
      involuntary, uncontrollable, or surprising crying than watching one on the
      ground, described in some social media as "altitude-adjusted lachrymosity
      syndrome" (AALS), or whether this is a pseudo-phenomena. Methods: Amazon
      Mechanical Turk survey participants (N = 1,084) living in the United States who
      had watched a film on a plane in the past 12 months were invited to complete an
      online survey. The main outcome measures were likelihood of crying in a logistic
      regression model including location of viewing, age, gender, genre of film,
      subjective film rating, annual household income, watching a "guilty pleasure"
      film, drinking alcohol, feeling tired or jetlagged, or having a recent emotional
      life event. Results: About one in four films induced crying. Watching a film on a
      plane per se does not appear to induce involuntary crying. Significant predictors
      of crying included dramas or family films, a recent life event, watching a
      "guilty pleasure", high film ratings, and female gender. Medical conditions, age,
      income, alcohol use, and feeling tired or jetlagged were not significant.
      Conclusion: People reporting the pseudo-phenomena of AALS are most likely
      experiencing "dramatically heightened exposure", watching as many films on a
      plane in a week's return trip as they would in a year at the cinema. Such
      perceptions are probably magnified by confirmation bias and further mentions in
      social media.

PMID- 29632744
TI  - Oligotrophic wetland sediments susceptible to shifts in microbiomes and mercury
      cycling with dissolved organic matter addition.
AB  - Recent advances have allowed for greater investigation into microbial regulation
      of mercury toxicity in the environment. In wetlands in particular, dissolved
      organic matter (DOM) may influence methylmercury (MeHg) production both through
      chemical interactions and through substrate effects on microbiomes. We conducted
      microcosm experiments in two disparate wetland environments (oligotrophic
      unvegetated and high-C vegetated sediments) to examine the impacts of plant
      leachate and inorganic mercury loadings (20 mg/L HgCl2) on microbiomes and MeHg
      production in the St. Louis River Estuary. Our research reveals the greater
      relative capacity for mercury methylation in vegetated over unvegetated
      sediments. Further, our work shows how mercury cycling in oligotrophic
      unvegetated sediments may be susceptible to DOM inputs in the St. Louis River
      Estuary: unvegetated microcosms receiving leachate produced substantially more
      MeHg than unamended microcosms. We also demonstrate (1) changes in microbiome
      structure towards Clostridia, (2) metagenomic shifts toward fermentation, and (3)
      degradation of complex DOM; all of which coincide with elevated net MeHg
      production in unvegetated microcosms receiving leachate. Together, our work shows
      the influence of wetland vegetation in controlling MeHg production in the Great
      Lakes region and provides evidence that this may be due to both enhanced
      microbial activity as well as differences in microbiome composition.

PMID- 29632745
TI  - Herbarium specimens can reveal impacts of climate change on plant phenology; a
      review of methods and applications.
AB  - Studies in plant phenology have provided some of the best evidence for large
      scale responses to recent climate change. Over the last decade, more than thirty
      studies have used herbarium specimens to analyze changes in flowering phenology
      over time, although studies from tropical environments are thus far generally
      lacking. In this review, we summarize the approaches and applications used to
      date. Reproductive plant phenology has primarily been analyzed using two summary
      statistics, the mean flowering day of year and first-flowering day of year, but
      mean flowering day has proven to be a more robust statistic. Two types of
      regression models have been applied to test for associations between flowering,
      temperature and time: flowering day regressed on year and flowering day regressed
      on temperature. Most studies analyzed the effect of temperature by averaging
      temperatures from three months prior to the date of flowering. On average,
      published studies have used 55 herbarium specimens per species to characterize
      changes in phenology over time, but in many cases fewer specimens were used.
      Geospatial grid data are increasingly being used for determining average
      temperatures at herbarium specimen collection locations, allowing testing for
      finer scale correspondence between phenology and climate. Multiple studies have
      shown that inferences from herbarium specimen data are comparable to findings
      from systematically collected field observations. Understanding phenological
      responses to climate change is a crucial step towards recognizing implications
      for higher trophic levels and large-scale ecosystem processes. As herbaria are
      increasingly being digitized worldwide, more data are becoming available for
      future studies. As temperatures continue to rise globally, herbarium specimens
      are expected to become an increasingly important resource for analyzing plant
      responses to climate change.

PMID- 29632746
TI  - Variation in the diversity and richness of parasitoid wasps based on sampling
      effort.
AB  - Parasitoid wasps are a mega-diverse, ecologically dominant, but poorly studied
      component of global biodiversity. In order to maximise the efficiency and reduce
      the cost of their collection, the application of optimal sampling techniques is
      necessary. Two sites in Auckland, New Zealand were sampled intensively to
      determine the relationship between sampling effort and observed species richness
      of parasitoid wasps from the family Ichneumonidae. Twenty traps were deployed at
      each site at three different times over the austral summer period, resulting in a
      total sampling effort of 840 Malaise-trap-days. Rarefaction techniques and non
      parametric estimators were used to predict species richness and to evaluate the
      variation and completeness of sampling. Despite an intensive Malaise-trapping
      regime over the summer period, no asymptote of species richness was reached. At
      best, sampling captured two-thirds of parasitoid wasp species present. The
      estimated total number of species present depended on the month of sampling and
      the statistical estimator used. Consequently, the use of fewer traps would have
      caught only a small proportion of all species (one trap 7-21%; two traps 13-32%),
      and many traps contributed little to the overall number of individuals caught.
      However, variation in the catch of individual Malaise traps was not explained by
      seasonal turnover of species, vegetation or environmental conditions surrounding
      the trap, or distance of traps to one another. Overall the results demonstrate
      that even with an intense sampling effort the community is incompletely sampled.
      The use of only a few traps and/or for very short periods severely limits the
      estimates of richness because (i) fewer individuals are caught leading to a
      greater number of singletons; and (ii) the considerable variation of individual
      traps means some traps will contribute few or no individuals. Understanding how
      sampling effort affects the richness and diversity of parasitoid wasps is a
      useful foundation for future studies.

PMID- 29632747
TI  - Bleeding in Locally Invasive Pelvic Malignancies: Is Hypofractionated Radiation
      Therapy a Safe and Effective Non-Invasive Option for Securing Hemostasis? A
      Single Institution Perspective.
AB  - INTRODUCTION:  Control of bleeding due to locally invasive disease is of
      paramount importance in the management of cancer patients. This study was
      undertaken to explore the outcomes of palliative intent hypofractionated
      radiation therapy (HRT) in advanced stage pelvic malignancies that presented with
      bleeding. METHODS:  This study enrolled patients treated with palliative intent
      hypofractionated radiation therapy from July 2015 to November 2017. In the
      inclusion criteria, all these patients had the common presenting complaint of
      bleeding from the tumor. These patients were not treated with radiation therapy
      before for the same indication. Patients with known bleeding disorders and those
      undergoing parallel interventions for bleeding control were excluded from the
      study. Bleeding was categorized based on the World Health Organization (WHO)
      scale for the classification of bleeding. Response assessment was classified into
      a complete response, partial response and no response. A comparison was made for
      the bleeding scale before and after HRT using the Wilcoxon signed rank test. The
      comparison of mean hemoglobin levels before and after the HRT was calculated by
      paired t-test. RESULTS:  Forty-two patients with advanced pelvic malignancies
      qualified for inclusion in the study after applying the inclusion/exclusion
      criteria. Among those analyzed, the median age was 67 years (range 37 - 95
      years). The male and female proportion was 38% and 62% respectively. Different
      cancers included uterine cancer 31%, cervical cancer 24%, bladder cancer 21%,
      rectal cancer 17% and vulvar cancer in 7%. The baseline bleeding scale in these
      cases was found to be grade 1 in 12%, grade 2 in 55% and grade 3 in 33% cases.
      The median dose in our cohort was 20 Gy in five fractions over one week (range
      was 8 Gy to 40 Gy). Following HRT, the WHO bleeding score at one month was
      recorded as grade 0 in 57%, grade 1 in 31%, grade 2 in 7%, grade 3 in 5% and
      grade 4 in none. Toxicity profile did not show any grade 3 or above acute
      toxicity in the study. Response rates were 57% complete response, 36% partial
      response and 7% no response. The mean hemoglobin level post-treatment versus pre
      treatment was found to be 9.6 g/dL versus 7.3 g/dL. CONCLUSIONS: 
      Hypofractionated radiotherapy was found to be a safe and effective non-invasive
      palliative treatment modality for securing hemostasis in advanced pelvic
      malignancies that presented with bleeding.

PMID- 29632748
TI  - Development of Growth Charts of Pakistani Children Aged 4-15 Years Using Quantile
      Regression: A Cross-sectional Study.
AB  - Background Growth charts are essential tools used by pediatricians as well as
      public health researchers in assessing and monitoring the well-being of pediatric
      populations. Development of these growth charts, especially for children above
      five years of age, is challenging and requires current anthropometric data and
      advanced statistical analysis. These growth charts are generally presented as a
      series of smooth centile curves. A number of modeling approaches are available
      for generating growth charts and applying these on national datasets is important
      for generating country-specific reference growth charts. Objective To demonstrate
      that quantile regression (QR) as a viable statistical approach to construct
      growth reference charts and to assess the applicability of the World Health
      Organization (WHO) 2007 growth standards to a large Pakistani population of
      school-going children. Methodology This is a secondary data analysis using
      anthropometric data of 9,515 students from a Pakistani survey conducted between
      2007 and 2014 in four cities of Pakistan. Growth reference charts were created
      using QR as well as the LMS (Box-Cox transformation (L), the median (M), and the
      generalized coefficient of variation (S)) method and then compared with WHO 2007
      growth standards. Results Centile values estimated by the LMS method and QR
      procedure had few differences. The centile values attained from QR procedure of
      BMI-for-age, weight-for-age, and height-for-age of Pakistani children were lower
      than the standard WHO 2007 centile. Conclusion QR should be considered as an
      alternative method to develop growth charts for its simplicity and lack of
      necessity to transform data. WHO 2007 standards are not suitable for Pakistani
      children.

PMID- 29632749
TI  - Commissioning and Evaluation of an Electronic Portal Imaging Device-Based In-Vivo
      Dosimetry Software.
AB  - This study reports on our experience with the in-vivo dose verification software,
      EPIgray(r) (DOSIsoft, Cachan, France). After the initial commissioning process,
      clinical experiments on phantom treatments were evaluated to assess the level of
      accuracy of the electronic portal imaging device (EPID) based in-vivo dose
      verification. EPIgray was commissioned based on the company's instructions. This
      involved ion chamber measurements and portal imaging of solid water blocks of
      various thicknesses between 5 and 35 cm. Field sizes varied between 2 x 2 cm2 and
      20 x 20 cm2. The determined conversion factors were adjusted through an
      additional iterative process using treatment planning system calculations.
      Subsequently, evaluation was performed using treatment plans of single and
      opposed beams, as well as intensity modulated radiotherapy (IMRT) plans, based on
      recommendations from the task group report TG-119 to test for dose reconstruction
      accuracy. All tests were performed using blocks of solid water slabs as a
      phantom. For single square fields, the dose at isocenter was reconstructed within
      3% accuracy in EPIgray compared to the treatment planning system dose. Similarly,
      the relative deviation of the total dose was accurately reconstructed within 3%
      for all IMRT plans with points placed inside a high-dose region near the
      isocenter. Predictions became less accurate than < 5% when the evaluation point
      was outside the treatment target. Dose at points 5 cm or more away from the
      isocenter or within an avoidance structure was reconstructed less reliably.
      EPIgray formalism accuracy is adequate for an efficient error detection system
      with verifications performed in high-dose volumes. It provides immediate intra
      fractional feedback on the delivery of treatment plans without affecting the
      treatment beam. Besides the EPID, no additional hardware is required. The
      software evaluates local point dose measurements to verify treatment plan
      delivery and patient positioning within 5% accuracy, depending on the placement
      of evaluation points.

PMID- 29632750
TI  - Use of Femoral and Sciatic Nerve Block Combination in Severe Emphysematous Lung
      Disease for Femoral Popliteal Arterial Bypass Surgery.
AB  - Regional anesthesia is a widely used anesthesia technique for high-risk patients
      with severe vascular or pulmonary diseases in which general anesthesia is
      considered harmful and should be avoided. In this case, we present the use of
      femoral-sciatic nerve block combination for a 65-year-old, ASA IV, male patient
      who had severe emphysematous lung disease and was planned for a right femoral
      popliteal arterial bypass surgery. He had severe pulmonary disease, hypertension,
      peripheral vascular disease, and was on clopidogrel treatment. Due to his
      existing comorbidities, regional anesthesia was considered the right method. The
      combination of femoral and sciatic nerve block was successfully used for the
      operation, which lasted for one hour and fifty minutes under sedation, and was
      continuously supplied with a propofol infusion. The patient was safely discharged
      to the surgical ward with no pain. The femoral block and sciatic block
      combination is described as one of the most useful, and at the same time, the
      most ignored anesthetic method. This technique is considered a standard technique
      and is often taught early in training; however, its use seems to be
      underestimated as there are only a few cases documented in Turkey. The aim of
      this case is to serve as a reminder of its significant value in patients who are
      not appropriate for general anesthesia and neuraxial blocks.

PMID- 29632751
TI  - Staged Image-guided Robotic Radiosurgery and Deferred Chemotherapy to Treat a
      Malignant Glioma During and After Pregnancy.
AB  - A 26-year-old pregnant woman with a fast-growing malignant deep-seated brain
      glioma was offered a therapeutic abortion to allow subsequent surgical resection.
      This option was refused by the mother, but the fast tumor growth placed the life
      of both mother and child at risk. A staged CyberKnife radiosurgery treatment was
      then planned, aiming to provide at least temporary tumor growth control and allow
      a safe delivery while keeping the doses received by the fetus well below the
      allowed doses. Growth control and the safe delivery of a healthy child were
      achieved after this first treatment. An intensive chemotherapy program based on
      the combination of Avastin, irinotecan, and Temodal was then started. Recurring
      tumor growth was treated with a second CyberKnife procedure while continuing the
      above chemotherapy protocol. At 43 months after the second CyberKnife procedure,
      the tumor had disappeared on magnetic resonance imaging. Neither mother nor child
      showed the neurological sequelae. Staged radiosurgery and deferred chemotherapy
      proved to be a safe and effective treatment to allow the delivery of a healthy
      child and the long-term control of an aggressive brain glioma.

PMID- 29632752
TI  - Celiac Disease and Concomitant Conditions: A Case-based Review.
AB  - Celiac disease is a chronic autoimmune disease with genetic predisposition,
      triggered by the ingestion of gluten. It has a wide range of clinical
      manifestations ranging from asymptomatic forms to classic presentation of
      malabsorption with diarrhea and abdominal cramps. Celiac disease can also present
      with several other concomitant disorders (at the time of diagnosis or during the
      course of celiac disease) such as: type 1 diabetes, inflammatory bowel disease,
      rheumatoid arthritis, thyroid disorders, nutritional deficiencies, and gram
      negative sepsis. We present a 57-year-old female with past medical history of
      rheumatoid arthritis, who presented to the emergency department with a complaint
      of chronic diarrhea, complicated by gram-negative sepsis. The family history of
      the patient was significant for celiac disease, type 1 diabetes, and rheumatoid
      arthritis. The patient was closely monitored and treated appropriately. In this
      case-based review, we explore different associated conditions of celiac disease
      in the literature, as well as the patient's risk of developing malignancy.

PMID- 29632753
TI  - Treatment of Trigeminal Neuralgia with Anti-viral Therapy for Zoster: A Case
      Report.
AB  - Varicella zoster virus can infect the trigeminal ganglion, but viral infection is
      not frequently considered as a cause of trigeminal neuralgia. This is a case of a
      woman whose trigeminal neuralgia remitted after being treated with valacyclovir
      for a thoracic zoster rash and later resolved entirely following administration
      of the zoster vaccine. Successful treatment of trigeminal neuralgia with anti
      viral therapies has not previously been reported. Zoster vaccination is currently
      recommended for adults over age 60, so patients with trigeminal neuralgia,
      especially those over the age of 60, should be encouraged to receive the
      varicella zoster vaccine.

PMID- 29632754
TI  - Efficacy of Homologous, Platelet-rich Plasma Dressing in Chronic Non-healing
      Ulcers: An Observational Study.
AB  - Background Chronic non-healing ulcers are a frequent problem in developing
      countries and represent a heavy burden to the patients because they lack the
      necessary growth factors (GFs) to maintain the healing process and are frequently
      complicated by super, added infections. Traditional therapies, such as regular
      dressings and wound debridement, cannot provide satisfactory results since these
      treatments are not able to provide the necessary GFs. Platelet-rich plasma (PRP)
      helps in enhancing the wound healing by releasing various GFs. The aim was to
      evaluate the efficacy of PRP dressing in the treatment of chronic non-healing
      ulcers. Methods Patients attending the outpatient department on a regular basis
      and those admitted as inpatients for chronic wound management were included in
      the study. It was an observational study done in a tertiary health center for a
      period of one year. All patients with eligible criteria were treated with PRP at
      twice-weekly intervals for a maximum of 10 dressings. At the end of the five
      weeks period, the reduction in the size of the ulcers (area and volume) was
      assessed. Results A total of 104 cases with chronic non-healing ulcers of various
      causes were treated with homologous PRP twice weekly for a maximum of 10
      dressings. In those 104 patients, non-healing ulcers in 85 patients (81.73%) were
      healed at the end of the last dressing. Non-healing ulcers in 13 patients (12.5%)
      were healed with skin grafting. Among those patients, the baseline mean ulcer
      area was 5.03 cm2. For each visit, there was a reduction in the ulcer area. At
      the end of the last visit, the mean ulcer area was 1.69 cm2, which was
      significant in this study. Conclusion Due to the lack of necessary GFs in chronic
      non-healing ulcers, PRP is safe and enhances the healing rates of chronic wounds,
      thereby reducing overall hospital stay and morbidity.

PMID- 29632755
TI  - Characterization of a Novel Revolving Radiation Collimator.
AB  - Introduction The ZAP-X is a novel self-contained and first-of-its-kind self
      shielded therapeutic radiation device dedicated to brain and head and neck
      radiosurgery. By utilizing a 2.7-MV linear accelerator and incorporating a design
      in which a beam stop and major mechanical elements serve a radiation shielding
      function, the Zap-X does not typically require a radiation bunker. The unique
      collimator design of the Zap-X is especially critical to the performance of the
      overall system. The collimator consists of a shielded tungsten wheel oriented
      with its rotational axis perpendicular to the beam's central axis; the goal of
      this design is to minimize radiation leakage. Beam selection is accomplished by
      rotating the wheel within its tungsten-shielded housing. We investigated
      radiation leakage from the Zap-X collimator to determine its compliance with
      internationally accepted standards using direct radiation measurements. Materials
      and methods To measure collimator leakage in the plane of the patient,
      equidistant measurement stations were defined in a plane perpendicular to the
      central beam axis (cax) 1 m from this axis (1 m from the radiation focal spot).
      To measure leakage alongside and adjacent to the accelerator, equidistant
      measurement stations were located 1 m from the cax along a line parallel to the
      cax in the plane of the collimator wheel and along a line parallel to the cax 90
      degrees offset from the first line of stations. Results Radiation leakage
      emanating from the collimating head of the linear accelerator in the patient
      plane ranged between 4.0 and 10.4 mR. Radiation along the linear accelerator
      (1000 R delivered in the primary beam) varied between 1.7 and 6.8 mR and
      constituted between 0.00017% to 0.00068% of the primary beam. The former
      radiation originated from X-ray target leakage, while the latter is produced
      directly by the linear accelerator and both contributed to the overall leakage
      radiation that would reach a patient. Discussion Due to the large diameter of the
      Zap-X tungsten collimator wheel and the massive Zap-X tungsten cylindrical
      collimator shield, the overall patient leakage is 0.00104% of the primary beam at
      a 1-m distance from the beam central axis in the patient plane. Leakage radiation
      in the patient plane is limited by the International Electrotechnical Commission
      (IEC) to 0.1% of the total primary radiation. Radiation leakage along the linear
      accelerator and the collimator housing was determined to be 0.00068% of primary
      radiation intensity. This leakage value is lower than the 0.1% leakage limit
      stipulated by IEC by more than a factor of 100. Conclusions Typically, an MV
      radiation therapy system minimizes exposure by utilizing a combination of device
      and structural shielding. However, the Zap-X has been uniquely designed to
      minimize the need for structural shielding. Our results indicate radiation
      leakage from the collimator meets internationally accepted standards as defined
      by the IEC.

PMID- 29632756
TI  - A Case of IgG4-related Sclerosing Mesenteritis.
AB  - A 60-year-old African-American male presented to the emergency department with
      abdominal pain and distention associated with decreased appetite and weight loss
      for several weeks. A computed tomography (CT) scan of the abdomen and pelvis
      showed an 8 cm mesenteric mass with surrounding stranding and poorly defined
      borders. The patient underwent exploratory laparotomy and complete resection of
      the mass since the frozen section could not give a definite diagnosis.
      Histopathology showed fibro-adipose tissue with lymphoid hyperplasia, vague
      nodular collections of foamy histiocytes with giant cell reaction, marked chronic
      inflammation, fat necrosis, and prominent sclerosis/fibrosis. Methenamine silver
      and acid-fast stains were negative for fungal and mycobacterial organisms
      respectively. Examination of tissue with immunohistostains showed increased
      immunoglobulin G4 (IgG4)-positive plasma cells. Other features observed were
      scattered areas of phlebitis, pockets of tissue eosinophilia, and focal storiform
      fibrosis leading to the diagnosis of IgG4-related sclerosing mesenteritis. The
      patient did not require steroids after the surgical resection and was disease
      free at six-month follow up.

PMID- 29632757
TI  - Constriction of the Stomach by an Unusual Peritoneal Band.
AB  - Compression of intraabdominal contents can occur due to anomalous congenital
      bands. Herein, we describe, to our knowledge, the first case of compression of
      the stomach by an anomalous band extending from the lesser omentum to the greater
      omentum. Relevant literature is reviewed and the clinical implications of such a
      case are described.

PMID- 29632758
TI  - Late-Onset Inflammatory Response to Hyaluronic Acid Dermal Fillers.
AB  - Objective: Even though injectable hyaluronic acid (HA)-based fillers are
      considered safe, rare complications, such as late-onset inflammatory reactions
      have been reported. Possible causes and effective treatments have not been
      formally described, so this work aims to discuss these and offer a formal
      protocol for treatment. Methods: This article presents 5 clinical cases of late
      onset inflammatory response occurring at least 3 months after uneventful
      injection of HA dermal filler. Results: Inflammation appeared spontaneously,
      usually 4-5 months after the last injection, but in 1 patient, almost 14 months
      later. One patient was injected at the same time with fillers manufactured by 2
      different technologies. In this case, all areas treated with the same filler
      showed diffuse swelling of inflammatory nature, whereas the lips, treated with
      the second filler brand, remained unaffected. Four patients reported a flu-like
      illness or gastrointestinal upset a few days before the onset of dermal filler
      inflammation. Conclusion: Late-onset inflammatory reactions to HA fillers may be
      self-limiting but are easily and rapidly treatable with oral steroids, and with
      hyaluronidase in the case of lumps. It is likely these reactions are due to a
      Type IV delayed hypersensitivity response. Delayed inflammation associated with
      HA fillers is nonbrand specific. However, the case where 2 different brands were
      injected during the same session, but only 1 brand triggered a hypersensitivity
      reaction, suggests that the technology used in the manufacturing process, and the
      subsequent differing products of degradation, may have an influence on potential
      allergic reactions to HA fillers.

PMID- 29632759
TI  - Vascularized Thymosternal Composite Tissue Allo- and Xenotransplantation in
      Nonhuman Primates: Initial Experience.
AB  - Background: Vascularized composite allotransplantation is constrained by
      complications associated with standard immunosuppressive strategies. Vascularized
      thymus and bone marrow have been shown to promote prolonged graft survival in
      composite organ and soft-tissue vascularized composite allotransplantation
      models. We report development of a nonhuman primate vascularized thymosternal
      composite tissue transplant model as a platform to address donor-specific immune
      tolerance induction strategies. Methods: Vascularized thymosternal allograft
      (skin, muscle, thymus, sternal bone) was transplanted between MHC-mismatched
      rhesus monkeys (feasibility studies) and baboons (long-term survival studies),
      with end-to-side anastomoses of the donor aorta and SVC to the recipient common
      femoral vessels. A male allograft was transplanted to a female's lower abdominal
      wall, and clinically applicable immunosuppression was given. Skin biopsies and
      immunological assays were completed at regular intervals, and chimerism was
      quantified using polymerase chain reaction specific for baboon Y chromosome.
      Results: Four allo- and 2 xenotransplants were performed, demonstrating
      consistent technical feasibility. In 1 baboon thymosternal allograft recipient
      treated with anti-CD40-based immunosuppression, loss of peripheral blood
      microchimerism after day 5 was observed and anticipated graft rejection at 13
      days. In the second allograft, when cutaneous erythema and ecchymosis with
      allograft swelling was treated with anti-thymocyte globulin starting on day 6,
      microchimerism persisted until immunosuppression was reduced after the first
      month, and the allograft survived to 87 days, 1 month after cessation of
      immunosuppression treatment. Conclusions: We established both allo- and xeno-
      composite vascularized thymosternal transplant preclinical models, which will be
      useful to investigate the role of primarily vascularized donor bone marrow and
      thymus.

PMID- 29632760
TI  - Novel Pressure-Sensing Smart Insole System Used for the Prevention of Pressure
      Ulceration in the Insensate Foot.
AB  - Wounds of the foot challenge reconstructive surgeons to manage multiple factors:
      sensibility, stability, and durability. In this article, we focus on the
      insensate foot, which poses challenges to wound prevention with its propensity to
      develop pressure ulceration. The authors present the innovative use of a pressure
      sensing smart insole system (SurroSense Rx, Orpyx Medical Technologies Inc.,
      Calgary, Canada) in the management of the insensate foot in a patient following
      foot reconstruction. The pressure-sensing smart insole system provided unique
      feedback to both patient and provider in ways that contributed to the prevention
      of pressure ulcer recurrence, as well as highlight the importance of prescribed
      footwear in both the affected and unaffected foot. Wearable real-time monitoring
      and feedback faces the challenge of patient adherence. Future studies are
      indicated to examine the specific behaviors that are associated with favorable
      outcomes and long-term behavior changes.

PMID- 29632761
TI  - Consensus Recommendations for Treatment Strategies in Indians Using Botulinum
      Toxin and Hyaluronic Acid Fillers.
AB  - Background: Indians constitute one of the largest population groups in the world.
      Facial anthropometry, morphology, and age-related changes in Indians differ from
      those of other ethnic groups, necessitating a good understanding of their facial
      structure and the required aesthetic treatment strategies. However, published
      recommendations specific to Indians are few, particularly regarding combination
      treatment. Methods: The Indian Facial Aesthetics Expert Group (19 dermatologists,
      plastic surgeons, and aesthetic physicians with a mean 15.5 years' aesthetic
      treatment experience) met to develop consensus recommendations for the cosmetic
      facial use of botulinum toxin and hyaluronic acid fillers, alone and in
      combination, in Indians. Treatment strategies and dosage recommendations (agreed
      by >= 75% of the group) were based on results of a premeeting survey, peer
      reviewed literature, and the experts' clinical experience. Results: The need for
      combination treatment increases with age. Tear trough deficiency is the most
      common midface indication in Indian women aged 20-40 years. In older women, malar
      volume loss and jowls are the most common aesthetic concerns. Excess medial soft
      tissue on a relatively smaller midface precedes age-related sagging. Hence, in
      older Indians, fillers should be used peripherally to achieve lift and
      conservatively in the medial zones to avoid adding bulk medially. The shorter,
      wider lower face requires 3-dimensional correction, including chin augmentation,
      to achieve increased facial height and the oval shape desired by most Indian
      women. Conclusions: These recommendations give physicians treating Indians
      worldwide a better understanding of their unique facial characteristics and
      provide treatment strategies to achieve optimal aesthetic outcomes.

PMID- 29632762
TI  - A Histological Comparison of Two Human Acellular Dermal Matrix Products in
      Prosthetic-Based Breast Reconstruction.
AB  - Background: Acellular dermal matrices (ADMs) are an integral component of breast
      reconstruction. The ideal matrix would be relatively immuno-inert, allow rapid
      vascularization, and be affordable. The purpose of this study was to
      histologically compare 2 commonly used ADM products. Methods: This is a
      prospective histological study of 17 patients (20 breasts) following prosthetic
      based breast reconstruction with ADM: Alloderm (LifeCell Corp, Branchburg, N.J.)
      or Cortiva (RTI Surgical, Alachua Fla.). Biopsies were taken from the dermal
      matrix and natural capsules surrounding the expander/implant during secondary
      surgery [Range, 72-694 days (mean, 217 days)]. Biopsy specimens were prepared via
      hematoxylin and eosin, Masson's trichrome, elastin, and transforming growth
      factor (TGF)-1 stains. Quantitative analysis of staining was performed with
      ImageJ software. The clinical outcome of each patient is analyzed in relation to
      capsule architecture and ADM performance. Results: There were 7 breasts in the
      Alloderm group and 13 in the Cortiva group. Both groups had similar demographic,
      aesthetic results, and complication profiles. The TGF-1 staining demonstrated
      significantly lower levels in the Cortiva capsules (P = 0.0139). The percentage
      of elastin and collagen are similar in the Cortiva, Alloderm, and natural peri
      implant capsules. The native capsules show a significantly greater number of
      blood vessels when compared with Cortiva and Alloderm (P = 0.0371 and P = 0.0347,
      respectively); however, there is no difference in vascular pattern between the 2
      dermal matrices. Discussion: Postoperatively, Cortiva demonstrates equal
      vascularity with less TGF-1 activation compared with Alloderm. The clinical
      success and complication profile were similar between the Alloderm and Cortiva
      patients.

PMID- 29632763
TI  - The Superiorly Based Partial Rectus Abdominis and External Oblique Flap: A New
      Technique for Breast Asymmetry Reconstruction.
AB  - Breast asymmetry has a wide spectrum of presentations with several employable
      strategies for surgical correction. Historically, the external oblique muscle has
      proven to be a versatile flap option for the reconstruction of both local and
      distant defects. It has also been described for use in breast reconstruction for
      coverage of the lower pole of implant prostheses. The external oblique muscle
      flap can be harvested in several ways to capture overlying fat and skin. In this
      study, we describe the use of a superiorly based partial rectus and external
      oblique flap for surgical correction of lower pole breast hypoplasia. This flap
      provides vascularized autologous volume to the lower pole of the breast with
      minimal donor morbidity. Other advantages of this flap are that it can increase
      the nipple to inframammary fold distance and lower the inframammary fold. This
      technique represents an evolution of an under-utilized flap and is the first
      study describing the use of the external oblique flap in the management of breast
      asymmetry.

PMID- 29632765
TI  - Venous Anastomosis for Prevention of Venous Congestion in Distally Based Flaps.
AB  - Background: Distally based flaps are useful for the treatment of skin defects of
      the extremities. However, congestion in the peripheral part of the flap due to
      reverse flow can cause partial flap necrosis. Previously, we reported on the
      effectiveness of venous anastomoses to rescue peripheral congestion of distally
      based flaps and applied this idea in a clinical setting. In this report, we
      present clinical cases of distally based flaps with venous supercharge
      anastomoses for changing the reverse venous flow into physiological flow, thereby
      reducing venous congestion. Methods: Four patients with skin defects of the
      extremities (2 cases with defects of the knee and the upper third of the lower
      leg, 1 case of the lower third of the lower leg, and 1 case of the distal third
      of the forearm) were treated with local flaps (2 cases with distally based
      greater saphenous venoadipofascial sartorius muscle combined flaps, 1 case with a
      distally based lesser saphenous venoadipofascial flap, and 1 case with a distally
      based ulnar artery perforator flap). In each reconstruction, 1 or 2 veins in the
      flaps were anastomosed with superficial veins in the recipient area to change the
      reverse venous flow into a normal, physiologic flow. Result: All flaps healed
      completely without any obvious venous congestion or flap necrosis. The coverage
      quality provided by these defects was satisfactory. Conclusions: Adding venous
      anastomoses may reduce the risk of venous congestion and improve the outcomes of
      the distally based flaps.

PMID- 29632764
TI  - Silicone Migration after Buttock Augmentation.
AB  - We present the case of a 30-year-old woman who presented with enlarged inguinal
      lymph nodes and sacral hyperpigmentation 4 months after gluteal augmentation with
      silicone implants. Inguinal lymph node biopsy revealed granulomatous
      lymphadenitis due to foreign material. Upon right buttock implant revision, a 1.5
      cm-thick capsule was noted with the absence of peri-implant inflammatory fluid
      and no macroscopic implant defects. Analysis of the implant by the manufacturer
      revealed a microscopic silicone leak. The patient's recovery was uneventful, and
      her symptoms resolved shortly after her reoperation.

PMID- 29632766
TI  - Quantification of Collagen Organization after Nerve Repair.
AB  - Background: Clinical outcomes after nerve injury and repair remain suboptimal.
      Patients may be plagued by poor functional recovery and painful neuroma at the
      repair site, characterized by disorganized collagen and sprouting axons. Collagen
      deposition during wound healing can be intrinsically imaged using second harmonic
      generation (SHG) microscopy. The purpose of this study was to develop a protocol
      for SHG imaging of nerves and to assess whether collagen alignment can be
      quantified after nerve repair. Methods: Sciatic nerve transection and epineural
      repair was performed in male rats. The contralateral nerves were used as intra
      animal controls. Ten-millimeter nerve segments were harvested and fixed onto
      slides. SHG images were collected using a 20* objective on a multiphoton
      microscope. Collagen fiber alignment was calculated using CurveAlign software.
      Alignment was calculated on a scale from 0 to 1, where 1 represents perfect
      alignment. Statistical analysis was performed using a linear mixed-effects model.
      Results: Eight male rats underwent right sciatic nerve repair using 9-0 Nylon
      suture. There were gross variations in collagen fiber organization in the
      repaired nerves compared with the controls. Quantitatively, collagen fibers were
      more aligned in the control nerves (mean alignment 0.754, SE 0.055) than in the
      repairs (mean alignment 0.413, SE 0.047; P < 0.001). Conclusions: SHG microscopy
      can be used to quantitate collagen after nerve repair via fiber alignment. Given
      that the development of neuroma likely reflects aberrant wound healing, ex vivo
      and/or in vivo SHG imaging may be useful for further investigation of the
      variables predisposing to neuroma.

PMID- 29632767
TI  - Prompt Referral in the Nonoperative Treatment of Obstetrical Brachial Plexus
      Injuries.
AB  - Background: Prompt physical and occupational therapy is crucial in managing
      nonsurgical candidates with obstetrical brachial plexus injuries (OBPI). The
      objective of our study was to identify newborns suffering from nonoperative OBPI
      in need of a "fast-track" evaluation by a multidisciplinary team. Methods: This
      is a retrospective review of patients with OBPI from June 1995 to June 2015. All
      nonsurgical candidates (Narakas class 1) were included in the study. The Gilbert
      score and the Medical Research Council grading system were used to measure
      shoulder and elbow function, respectively. The relationship between shoulder and
      elbow functional outcomes and time delay to consultation was studied using
      analysis of variance and Welch's tests. Various subgroups were studied based on
      OBPI risk factors: maternal diabetes, birth weight >4 kg, use of forceps,
      asphyxia, multiple comorbidities, and Apgar score at 1 and 5 minutes. Results: A
      total of 168 patients were included in this study. Mean follow-up time was 313.8
      weeks (minimum: 52; maximum: 1072; SD: 228.1). A total of 19 patients had an
      Apgar scores <7 at 5 minutes. Time delay between birth and the first consult to
      our clinic had an impact on shoulder outcome in the subgroup of newborns with
      Apgar scores <7 at 5 minutes. Conclusions: The subgroup of newborns with an Apgar
      score <7 at 5 minutes shows improved long-term shoulder function when promptly
      examined by an OBPI clinic. We recommend a "fast-track" referral for this time
      sensitive population.

PMID- 29632768
TI  - Examining Length of Hospital Stay after Microsurgical Breast Reconstruction:
      Evaluation in a Case-Control Study.
AB  - Background: While possessing numerous benefits, microsurgical breast
      reconstruction is associated with longer operative times and post-operative
      hospital length of stay compared to implant-based reconstruction. We therefore
      evaluate factors associated with increased length of stay (LOS) after
      microsurgical breast reconstruction with a case-control study design. Methods:
      All patients undergoing immediate or delayed abdominally-based microsurgical
      breast reconstruction over a two-year time period were identified. Risk factors
      associated with LOS greater than or equal to 5 days were identified. Results: A
      total of 116 patients undergoing immediate or delayed abdominally-based
      microsurgical breast reconstruction were identified. Of these, 86 (74.1%) had a
      LOS of 4 days or less (mean: 3.70 days) while 30 (25.9%) had a LOS of 5 days or
      greater (mean: 5.50 days).With regards to patient demographics and intra
      operative factors, patients with a LOS of 5 days or greater were significantly
      more likely to have diabetes mellitus (p < 0.0001), undergo bilateral
      reconstruction (p = 0.0003) and total mastectomy (p < 0.0001), and have a longer
      operative time (p < 0.0001) while significantly less likely to undergo post
      operative radiation (p = 0.0421). Notably, there was no significant difference
      between the groups in terms of follow-up time, or time since breast
      reconstruction (p = 0.0600).With regards to reconstructive complications,
      patients with LOS of 5 days of greater were significantly more likely to
      experience abdominal donor site abscess (p < 0.0001), breast hematoma (p =
      0.0186), and return to the operating room for flap compromise (p < 0.0001).
      Conclusions: Multiple patient-specific, intra-operative, and post-operative
      outcomes factors are associated with increased length of stay with immediate and
      delayed microsurgical breast reconstruction.

PMID- 29632769
TI  - A Modified Bilhaut-Cloquet Procedure for Zigzag Thumb Polydactyly Types III and
      IV.
AB  - Background: A review of the English literature over the least 43 years revealed
      only a total of 53 cases of Wassel types III, IV, and VII treated by the Bilhaut
      Cloquet (B-C) procedure. Furthermore, the detailed results and range of motion
      were only given in 2 series (a total of 9 cases). Methods: Four cases of Wassel
      types III and IV thumb duplications with zigzag deformity were treated with a
      modified B-C procedure. The main modification was minimal central resections at
      the joints aiming for joint preservation to improve the postoperative range of
      motion of the new thumb. Results: The results showed an excellent overall
      functional score (Tada score of 5 of 5 in all cases). The mean range of motion at
      the metacarpophalangeal joint was excellent (60 degrees ), but the mean at the
      interphalangeal joint was only 20 degrees . Cosmetically, all thumbs were "too
      wide" and a panel of 3 hand surgeons scored the cosmetic result (0-10 scoring
      system) between 5.7 and 6.7. No secondary procedures were done, and all parents
      were "very satisfied" despite the wide thumbs and split nails. This was
      attributed to the presence of an ugly preoperative zigzag appearance, and hence
      the comparative postoperative appearance was satisfactory. Conclusion: The
      modified B-C procedure gives a satisfactory function, but the cosmetic outcome is
      suboptimal.

PMID- 29632770
TI  - Laterality and Left-sidedness in the Nose, Face, and Body: A New Finding.
AB  - Background: Asymmetry is a common occurrence in bilaterian animals, particularly
      human beings. Through examination of patients and their photographs during
      rhinoplasty, we noted wider left-sided nasal and facial features in most
      patients. This observation led us to hypothesize that this might be consistent to
      the whole body. Methods: We conducted a study in 3 parts to test the question
      above. First, we analyzed operating notes of 50 rhinoplasty patients to determine
      the wider side of the upper, middle, and lower thirds of the nose. Second, we
      analyzed the width of the face and chest wall in 31 patients to discern any
      correlation between facial and bodily asymmetry. Third, computerized tomographic
      scans of the thorax and body of 48 patients were studied to measure the width of
      the hemithorax and hemipelvic bone. Results: (1) Upper vault width was wider on
      left side (78%). Left middle vault width was wider (88%). The lower lateral
      cartilage, lateral crura convexity was more prominent on left side (48%), and a
      wider scroll area was found and trimmed in 21 (left) and 0 (right) cases. The
      alar base was wider on left side (56%). (2) In the body and face analysis, 64.5%
      had a wider left-sided face and body. (3) In the computed tomographic scan
      analysis, same-sided thorax and pelvis asymmetry was seen (85.35%), 33 and 7 of
      which were left- and right-sided, respectively. Conclusion: We observed
      generalized asymmetry of the face and body with left-sided predominance.

PMID- 29632771
TI  - Progressive Tightening of Pulley Sutures for Primary Repair of Large Scalp
      Wounds.
AB  - Scalp defects greater than 2 cm in diameter are not usually amenable to primary
      closure and require local tissue rearrangement, grafting, tissue expansion, or
      prolonged second intention healing. Scalp flap reconstruction is a significant
      undertaking that requires elevation of a total flap surface area that is 3-6
      times the size of the defect, often involves profuse bleeding, and can be
      challenging to perform without conscious sedation or general anesthesia.
      Anticoagulated and medically complex patients pose additional challenges and
      limit options for treatment. The pulley suture uses the mechanical advantage of
      the pulley to distribute tension across a wound and is useful in areas of high
      tension such as scalp wounds. For scalp wounds greater than 2 cm, pulley sutures
      are placed along the length of the wound. An assistant exerts equal tension on
      the pulley sutures, and the surgeon sequentially ties the sutures. The sutures
      are tightened and retied weekly until complete scalp closure is achieved. The
      pulley sutures can be used for rapid primary closure of scalp wounds up to 2.5
      3.0 cm in diameter under local anesthesia. For scalp wounds larger than 3 cm, we
      have also found that pulley sutures can be progressively tightened yielding
      additional tissue expansion every week. Scalp wounds greater than 3.0 cm can be
      easily closed via primary repair and weekly tightening of pulley sutures without
      the need for flap reconstruction, traditional tissue expander placement, or
      second intention healing.

PMID- 29632772
TI  - No Vertical Scar Breast Weight Transfer.
AB  - Women desire beautiful breasts that are functional, pain free, and without
      foreign material. Vertical scars, insufficient elevation, inadequate upper pole
      fullness, nipple numbness, and loss of breast feeding are undesirable. Relieving
      pain attributed to enlarged breasts has required significant tissue removal.
      Software analysis of chest images, physical measurements, and desires are
      combined to generate a surgical blueprint. The breast is divided horizontally
      into two components preserving the neurovascular supply and major lactiferous
      ducts. The skin flap cephalad to the areola provides external coverage. The
      areola remains attached to a deepithelialized mound, which is rotated into a
      cone. Dermal straps originating from the base of the cone are looped through the
      pectoralis major muscle and the cone repeatedly. Weight transfer to the
      pectoralis major muscles eliminates pain in 54% and decreases pain in 38%.
      Incisions are concealed at the areola cutaneous junction and in the shadow of the
      breast. Upper pole fullness increased in 86% without implants or fat transfer.
      Nipple sensation was increased in 37% and unchanged in 44%. Overall results were
      excellent in 50% and good in 36%. Complications consisted of dog-ears,
      periareolar infection, and fat necrosis. No patient required a return to the
      operation room. Combing computer-aided design with plastic surgical principles
      creates beautiful, functional breasts without foreign material. Vertical scars
      are avoided, and weight transfer relieves pain.

PMID- 29632773
TI  - Descriptive Analysis of the Arterial Supply to the Auricle in Patients with
      Unilateral Microtia.
AB  - Background: Microtia is a congenital auricular deformity that occurs in 1:5,000
      10,000 births. It can cause severe impairment to the patient's self-esteem and
      problems regarding social integration. Multiple measures have been described in
      attempt to better operative outcomes of these patients. We used computed
      tomography (CT) angiography to analyze the vascular pattern of the auricular
      region before surgery. Methods: Fourteen patients with unilateral microtia were
      included. All underwent CT angiogram plus tridimensional reconstruction. Both
      healthy and microtic auricles were analyzed descriptively in terms of main
      arterial supply, pattern, diameter of subbranches, and angulation. The sample was
      divided in 2 age groups for better understanding of the data. Results: Blood
      supply to the auricle was found to depend on 2 main vessels: temporal superficial
      artery (TSA) and its subbranches (superior, middle, and lower branch) and
      posterior auricular (PA) artery. In the microtic group, TSA was the dominant
      artery in 13 of 14 cases (92%). Superior, middle, and inferior branches were
      present in 4, 3, and 0 cases, respectively. Three of the microtic auricles
      presented supply from PA artery, from which in 1 case, it represented the only
      supply to the region. Conclusions: There is wide variability in the blood supply
      of both healthy and microtic auricles; however, we were able to identify some
      tendencies in our sample. Further research is needed to prove the benefit of a
      preoperative imaging study in these patients. Still, in our experience, we found
      it useful as a complement for surgical planning.

PMID- 29632774
TI  - Split Tolerance in a Murine Model of Heterotopic En Bloc Chest Wall
      Transplantation.
AB  - Background: Congenital and acquired chest wall deformities represent a
      significant challenge to functional reconstruction and may impact feasibility of
      heart transplantation for patients with end-stage organ failure. In the recent
      past, the concept of replacing like-with-like tissue by using vascularized
      composite allografts (VCA) has been enthusiastically employed for reconstruction
      of complex tissue defects. Methods: In this study, we introduce a novel murine
      model for en bloc chest wall, heart, and thymus transplantation and thereby the
      use of complex tissue allografts for reconstruction of both chest wall defects
      and also end-stage organ failure. Additionally, this model allows us to study the
      features of combined vascularized bone marrow (VBM), thymus, and heart
      transplantation on allograft survival and function. Heterotopic chest wall,
      thymus, and heart transplants were performed in untreated syngeneic and
      allogeneic combinations and in allogeneic combinations treated with costimulation
      blockade (CTLA4-Ig and MR-1). Results: Indefinite (ie, 150 d, N = 3) graft
      survival was observed in syngeneic controls. In untreated recipients of
      allogeneic grafts, the skin component was rejected after 10 (+/-1) days, whereas
      rejection of the heart occurred after 13 (+/- 1) days (N = 3). Costimulation
      blockade treatment prolonged survival of the heart and chest wall component (130
      d, N = 3) as well as the VBM niche as evidenced by donor-specific chimerism
      (average: 2.35 +/- 1.44%), whereas interestingly, the skin component was rejected
      after 13 (+/-1) days. Conclusion: Thus, this novel microsurgical model of VCA
      combined with solid organ transplantation is technically feasible and results in
      split tolerance when treated with costimulatory blockade.

PMID- 29632775
TI  - A Systematic Review of Autologous Platelet-Rich Plasma and Fat Graft Preparation
      Methods.
AB  - Background: The addition of platelet-rich plasma (PRP) to adipose tissue may
      improve fat graft survival, although graft retention rates vary markedly between
      studies. To what extent this outcome heterogeneity reflects differing
      methodological factors remains unknown. This systematic review aims to synthesize
      and critically review methodological approaches to autologous PRP and fat
      cotransplantation in both human and animal studies. Methods: In accordance with
      PRISMA guidelines, Ovid MEDLINE, Scopus, and Cochrane Library databases were
      searched from inception to April 2017. Data were extracted from all in vivo
      studies involving autologous PRP and fat cotransplantation. A secondary aim was
      to assess reporting of technical detail; authors were not contacted to provide
      missing data. Results: From 335 articles, 23 studies were included in the
      qualitative synthesis. Some 21 were performed in humans and 2 in rabbits. Six
      studies were randomized control trials; the remainder reported on observational
      data. Methods of PRP extraction and activation varied markedly between studies.
      Fat graft preparation was comparatively more consistent. Methods of PRP and fat
      mixing differed significantly, especially with regards to relative volume/volume
      ratios. Conclusions: Our study represents the first systematic review of
      methodological factors in autologous PRP and fat cotransplantation. It
      demonstrates that technical factors in graft preparation and administration vary
      significantly between in vivo studies. Such methodological heterogeneity may
      explain observed differences in experimental and clinical outcomes. Reporting of
      key procedural information is inconsistent and often inadequate. These issues
      make meaningful evaluation of the PRP-enhanced fat grafting literature difficult
      and may limit its translation into clinical practice.

PMID- 29632776
TI  - Active Voluntary Contraction of the Ruptured Muscle Tendon during the Wide-awake
      Tendon Reconstruction.
AB  - Purpose: The purpose of this study was to measure the active voluntary
      contraction distances of ruptured musculotendinous units during wide-awake tendon
      reconstruction surgery and to investigate the relationships between active
      contraction distance and the passive distraction distance and the time elapsed
      before reconstruction. Methods: The passive distraction distance and active
      contraction distance of 36 tendons of 22 patients who underwent forearm tendon
      transfer or tendon graft during wide-awake surgery were measured. Results: The
      passive distraction distance was significantly related to the active contraction
      distance of the ruptured musculotendinous unit (r = 0.60, P < 0.05). The passive
      distraction distance accounted for approximately half of the total excursion of
      the musculotendinous unit. There was no significant correlation between each
      distance and the time elapsed before reconstruction. Conclusions: The passive
      distraction distance was significantly related to the active contraction distance
      of the ruptured musculotendinous unit in vivo during wide-awake surgery. Active
      musculotendinous unit contraction distance may be a useful index to evaluate
      ruptured musculotendinous unit degeneration and donor muscle function in standard
      tendon reconstruction. This study suggested that the advantages of the wide-awake
      approach were not just as a clinical tool but also as an in vivo research tool.

PMID- 29632777
TI  - Successfully Closing an Acquired Palatal-fistula Using a Turnover Flap from a
      Previously Transferred Forearm-free-flap.
AB  - Palatal fistula between the oral and nasal cavities occurs in about 20% of
      palatal repairs after oncologic resection. Although healing by secondary
      intention may be employed as an initial strategy, persistent nonhealing
      symptomatic fistula necessitates intervention. Folded free flap used for primary
      repair of palatectomy defects enables placement of epithelialized tissue on both
      the oral and nasal cavities. In case of acquired palatal fistula, a turnover flap
      can be easily created, based on the free margin of the folded forearm free flap
      to serve as a reconstructive lifeboat.

PMID- 29632778
TI  - Efficacy of Tensed and Straight Free Jejunum Transfer for the Reduction of
      Postoperative Dysphagia.
AB  - Background: Free jejunal transfer (FJT) is a standard method of reconstruction
      after total pharyngo-laryngo-cervical esophagectomy (TPLE) in patients with
      advanced head and neck cancer. However, it is related to various degrees of
      postoperative swallowing dysfunction. This study aimed to assess whether the
      tensed and straight FJT method results in a reduced rate of postoperative
      dysphagia compared with historical controls. Methods: Patients who were
      undergoing FJT after TPLE for squamous cell carcinoma of the hypopharynx or
      cervical esophagus were enrolled. The primary endpoint was the rate of not
      developing dysphagia within 6 months of the surgery, and we compared this value
      with that obtained from historical data of patients who underwent FJT. The
      secondary endpoint was the rate of developing surgical complications. Results:
      Although 128 patients were registered between August 2012 and July 2015, 7 were
      excluded based on the exclusion criteria. Of the remaining 121 patients, FJT with
      the craniocaudally tensed and straight method was performed in all patients. The
      rate of not developing dysphagia and its 95% confidence interval (CI) were 66.1%
      and 57.0-74.5%, respectively. The lower limit of the CI was higher than the
      prespecified threshold value of 50.0%. The rate of developing complications of
      total necrosis of the jejunum was 3.3%, cervical infection was 9.9%, and major
      anastomotic leakage was 4.1%. Conclusions: Our findings revealed that the
      proportion of postoperative dysphagia decreased in patients who underwent tensed
      and straight FJT. This method may become the standard surgical method in
      reconstruction of defects after TPLE.

PMID- 29632779
TI  - Vascular Reconstruction in a Neonate after Iatrogenic Injury during Cardiac
      Catheterization.
AB  - As technology and interventional techniques continue to evolve, both the volume
      and complexity of cardiac catheterizations will increase, leading to a rise in
      the number of complications. One of the most morbid complications of cardiac
      catheterization is vascular injury. We report the case of a 31-day-old, 3.0-kg
      infant with hypoplastic left heart syndrome who experienced a left common iliac
      artery disruption during cardiac catheterization resulting in a retroperitoneal
      hemorrhage. The extent of the vascular injury combined with the vessel caliber
      posed a technically challenging surgical scenario. Ultimately, the vascular
      supply to the left lower extremity was reconstructed by the plastic surgery team
      with a reverse autologous vein graft. To our knowledge, this multidisciplinary
      approach with the involvement of plastic surgery represents a unique case.

PMID- 29632780
TI  - Internal Mammary Vessels' Impact on Abdominal Skin Perfusion in Free Abdominal
      Flap Breast Reconstruction.
AB  - Background: Wound healing problems at the donor site in free abdominal flap
      breast reconstruction cause significant morbidity to patients. No studies have
      investigated what impact the use of the internal mammary artery in free abdominal
      flap breast reconstruction has on abdominal skin perfusion. We hypothesized that
      harvesting the internal mammary vessels (IMV) has a negative effect on abdominal
      skin perfusion. Methods: The abdomen and anterior thoracic wall of 17 patients
      scheduled for secondary free abdominal flap breast reconstruction using IMV was
      pre-, intra-, and postoperatively examined with dynamic infrared thermography.
      Qualitative and quantitative analyses of the rate and pattern of recovery in
      Huger's vascular zones were made with each patient being its own control. Zone
      III on the side where IMV were used was numbered zone IV. The contralateral zone
      III was used as reference. Results: Postoperative abdominal skin perfusion in
      zone IV was always significantly reduced compared with zone III (1-tailed t test,
      P < 0.05). The difference between zones II and III was statistically significant
      for day 1 and 3, but not for day 6 (2-tailed t test, P < 0.05). Skin perfusion in
      zones II and IV increased during consecutive postoperative days with an increase
      of hot spots in these areas. Conclusions: Using the IMV in free abdominal flap
      breast reconstruction had a significant effect on abdominal skin perfusion and
      may contribute to abdominal wound healing problems. The reperfusion of the
      abdominal skin was a dynamic process showing an increase in perfusion in the
      affected areas during the postoperative days.

PMID- 29632781
TI  - Combining Autologous and Prosthetic Techniques: The Breast Reconstruction Scale
      Principle.
AB  - Background: The latissimus dorsi (LD) flap remains a good option for immediate or
      delayed breast reconstruction. The main limitation of this flap is the small
      volume provided. To improve the reconstructed breast volume, the LD flap is
      usually combined with a breast implant. Recently, fat grafting to the LD flap was
      described to maximize flap volume and obtain a totally autologous breast
      reconstruction. We report our experience with hybrid breast reconstruction using
      both breast implants and fat-enriched latissimus dorsi (FELD) flaps. Methods:
      Between 2013 and 2016, 74 patients underwent breast reconstruction with FELD
      flaps only or FELD flaps combined with a breast implant. The LD flap was
      harvested as previously described. Donor sites for fat harvesting were chosen
      according to each patient's natural fat distribution. Fat was harvested,
      centrifuged, and injected into the LD flap. After fat grafting, breast sizers
      were employed to determine the final breast volume when the addition of an
      implant was indicated. Results: Good cosmetic outcomes were achieved in all
      cases, with a mean follow-up of 2.1 years. No patients had cancer reoccurrences.
      Four patients experienced a seroma of the LD donor site, 1 had a breast hematoma,
      and 1 developed Baker grade III capsular contracture. One year postoperatively, a
      clinically relevant area of fat necrosis was observed in 1 patient and was
      surgically treated. Additional fat grafting sessions were required in 3 cases.
      Conclusion: In elected cases, a FELD flap alone or in combination with a small
      implant is a valuable technique for breast reconstruction surgery.

PMID- 29632782
TI  - Ultrasound Diagnosis and Treatment of Breast Lumps after Breast Augmentation with
      Autologous Fat Grafting.
AB  - Background: Breast augmentation with autologous fat has been performed in Japan
      for over 30 years. However, complications include breast lumps and oil cysts.
      Such breast lumps greatly reduce patient satisfaction, and are currently
      difficult to diagnose and treat for many cosmetic surgery clinics. This study
      aimed to elucidate the effectiveness of ultrasound diagnosis and treatment of
      patients with breast lumps after breast augmentation with autologous fat
      grafting. Methods: We used diagnostic and therapeutic ultrasound to examine 256
      patients with breast lumps between April 2012 and April 2017. We determined the
      nature, size, and location of the maximal lump. Breast lumps were classified into
      five types: cystic, complex, solid, calcification, and unclassifiable. The method
      of treatment (including fine-needle aspiration, VASER liposuction, lumpectomy,
      and extended lumpectomy) was selected according to the lump type, and the
      efficacy of treatment was determined by postoperative palpation and ultrasound.
      Results: A total of 198 patients (198/256, 77%) requested treatment. Cystic lumps
      (79/256, 31%) were treated by fine-needle aspiration. VASER liposuction was used
      to treat complex (64/256, 25%) and solid lumps (50/256, 19%). Calcification
      (58/256, 23%) and unclassifiable lumps (5/256, 2%) were removed via periareolar
      incision. There were no serious complications. In all cases, the lumps were no
      longer palpable after treatment, and ultrasound showed that they had either
      contracted or disappeared. Conclusions: The appropriate treatment for breast
      lumps after breast augmentation with autologous fat grafting must be selected
      according to the nature of the lumps. Ultrasound is essential for diagnosing the
      breast lump type and determining the best treatment.

PMID- 29632783
TI  - Intentional Lower Pole Rotation of Anatomic Breast Implants in Chest Wall
      Deformities.
AB  - Several methods have been described for the correction of congenital thoracic
      wall deformities. Our aim was to investigate the feasibility and clinical results
      of using standard anatomic breast implants with modified anatomic positioning
      according to the defect in congenital thoracic wall deformities. Between 2014 and
      2015, 5 patients diagnosed with pectus excavatum (PE, n = 4) or pectus carinatum
      (PC, n = 1) and breast asymmetry or hypoplasia were evaluated. In all patients, a
      submammary incision and dual-plane subpectoral placement of texturized, anatomic
      implants were performed. In patients with PE, the lower pole of the implant was
      positioned medially to compensate for the caved chest. In patients with PC, the
      lower pole of the anatomic implant was positioned laterally to compensate for the
      prominent sternum. Outcome measures were satisfaction, minor and major
      complications, and morbidity. The mean surgery time was 95 +/- 14 minutes, and
      the mean implant volume was 287 +/- 56 cm3 (273 +/- 60 cm3 on the right side and
      305 +/- 60 cm3 on the left side). After a median follow-up of 25 months (range: 2
      35), all patients healed uneventfully, and a satisfactory correction of the
      thoracic wall deformity was achieved. Thus, by adjusting the lower pole of
      anatomic breast implants in a horizontal plane according to the thoracic defect,
      we showed satisfactory results. Our technique has a low complication rate and can
      be recommended for the correction of mild to moderate PE or PC.

PMID- 29632784
TI  - Autologous Fat Transfer for Facial Rejuvenation: A Systematic Review on
      Technique, Efficacy, and Satisfaction.
AB  - Background: Parallel to the steady decline in surgical aesthetic procedures to
      the face, dermal fillers seem to have gained a more prominent place in facial
      rejuvenation over the last couple of years. As a dermal, facial filler,
      autologous fat transfer (AFT) seems to have real potential because of the
      biocompatibility of adipose tissue besides being a procedure with few and
      primarily minor complications. This systematic review aims to evaluate the
      available evidence regarding the safety and effectiveness of AFT for facial
      rejuvenation. Method: A systematic review after the Preferred-Reporting-Items-for
      Systematic-Reviews-and-Meta-Analysis (PRISMA) statement was conducted. MEDLINE,
      Embase, and Cochrane Library were searched up to December 2016, with no language
      restrictions imposed. Case series, cohort studies, and randomized controlled
      trials (RCTs) reporting on relevant outcomes were included. Results: Eighteen
      clinical articles were included, reporting on 3,073 patients in total over a mean
      follow-up period of 13.9 months. Meta-analysis showed an overall complication
      rate of 6% (95% CI 3.0-14.0), with hematoma/ecchymosis (5%), fat necrosis/oil
      cysts (2%), and irregular fat distribution and scars (both 2%) being among the
      most reported. No major complications were reported, and the overall patient
      satisfaction rate was 81%. Conclusion: Although the evidence in this systematic
      review is still limited and plagued by heterogeneity between studies, AFT seems
      to be a promising method in facial rejuvenation with fewer complications than
      other fillers and high patient satisfaction rates. Further large-cohort,
      preferably multicenter, RCTs should substantiate these results through
      quantifiable volumetric assessment tools and validated patient questionnaires,
      while adhering to predetermined nomenclature in terms of complications.

PMID- 29632785
TI  - Complete Lower Lip Reconstruction with a Large Lip Switch Flap and a Composite
      Modiolus Advancement Flap.
AB  - Total loss of the lower lip is debilitating and poses a reconstructive challenge.
      Aiming to restore oral continence and function and also cosmetic appearance, a
      successful reconstruction has a huge impact on the quality of life for the
      individual patient. Early sources of local tissue rearrangement for lip
      reconstruction date back 3000 years, with earliest reports of lip switch
      procedures more than 2 centuries ago in Europe, when noma was still endemic in
      Europe, indicating that the anatomy was better understood by the barber surgeons
      of the past than we like to acknowledge. We are still faced with such challenging
      cases all over the world where resources are limited. Our current understanding
      of perforator anatomy and blood supply makes more frequent revisits to flaps of
      the past with modern advances. Innovative solutions are imperative for salvage,
      and old ideas tend to reappear when they prove to be useful. Herein, we describe
      in open access a new reconstructive method where we combined a large lip switch
      flap together with a composite advancement modiolus flap to reconstruct a whole
      lower lip and the donor defect of the upper lip all at once, a procedure that is
      simple to perform and works in settings where it is greatly needed.

PMID- 29632786
TI  - Aesthetic Refinements after Radial Free Flap Phalloplasty: Optimizing the Donor
      Site and the Phallus.
AB  - Background: Phalloplasty with radial forearm flap is the gold standard for female
      to-male sex reassignment surgery. However, it leaves a stigmatizing forearm scar,
      and as the new phallus is created with the forearm's skin and fat, it does not
      look like that of a biological man. The aesthetic appearance of the donor site
      and the neophallus can be optimized after phalloplasty. In this study, we review
      refinement techniques (RTs) performed after radial forearm flap phalloplasty.
      Methods: We present a historical cohort of patients who underwent the following
      RTs: forearm fat grafting and localized laser in the forearm's scars, and
      micropigmentation of the neophallus. Patient's aesthetic satisfaction was
      evaluated using the Patient and Observer Scar Assessment Scale for the forearm's
      refinements and the Male Genital Self-Image Scale for the neophallus. Results:
      Between January 2014 and January 2016, 8 patients underwent forearm fat grafting
      with localized laser, and 7 patients micropigmentation of the neophallus after
      radial flap phalloplasties. All Patient and Observer Scar Assessment Scale
      parameters showed a statistically significant reduction between preoperative and
      postoperative values. Male Genital Self-Image Scale survey showed that all
      patients felt positively about their genitals after micropigmentation. Patients
      who underwent refinement procedures were highly satisfied with the aesthetic
      outcome and felt more confident. They also claim that they would choose to have
      the refinement procedure done again. Conclusions: The proposed RTs are minimally
      invasive interventions to complement and enhance female-to-male sex reassignment
      surgery with very few complications and excellent aesthetic results of both the
      forearm scars and the constructed phallus.

PMID- 29632787
TI  - Foreign Body Reaction Mimicking Sarcoma.
AB  - Foreign body reaction can sometimes mimic the features of sarcoma. A 42-year-old
      patient was referred to our department for a rapidly growing subcutaneous mass in
      the posteromedial aspect of the lower leg. Ultrasonography and magnetic resonance
      imaging were highly suggestive for soft tissue sarcoma. The patient underwent
      surgical resection. The histho-pathologic diagnosis found that the supposed
      sarcoma was an inflammatory pseudo-tumor, also referred to as "gossypiboms".
      Surgeons must be aware that, in some cases, the imaging cannot reliably
      distinguish between sarcoma and foreign body reaction.

PMID- 29632788
TI  - Biodynamic Excisional Skin Tension Lines for Excisional Surgery of the Lower Limb
      and the Technique of Using Parallel Relaxing Incisions to Further Reduce Wound
      Tension.
AB  - Background: Closing of defects of the lower limb after skin cancer excision poses
      a challenge in lower limb skin. Although the concept of relaxed skin tension
      lines has been established as ideal on the face, on the lower limb there remains
      confusion between Langer's lines and wrinkle lines, and this study was done with
      the task of identifying and mapping biodynamic excisional skin tension (BEST)
      lines on the lower limb. Methods: Following studies on BEST lines elsewhere on
      the body, the author investigated BEST lines on the lower limb. Using a specially
      designed tensiometer, inherent skin tension (pretension) and wound-closing
      tension were studied along with the force needed to bring the wound edges
      together after excision of a lesion in 23 cases with defects ranging from 1.5 to
      4.5 cm in diameter. Skin tension measurements of skin lines (relaxed skin tension
      lines (RSTL) versus BEST) and vertical closure (BEST) versus vertical closure
      with a parallel relaxing incision were undertaken and followed by statistical
      analyses utilizing the paired t test and the unpaired Student's t tests. Results:
      BEST lines run in the vertical direction on the lower limb, that is, closure in a
      vertical direction resulted in a statistically significant reduction in closing
      tension when compared with other directions. Using a parallel relaxing incision
      can offer further reduction in tension, if needed. Conclusion: BEST lines of the
      lower limb are discussed, and a new technique of using parallel relaxing
      incisions to achieve closure of larger defects is also presented as an
      alternative to cutaneous flaps or grafts in the lower limb.

PMID- 29632789
TI  - Changes in Sunken Eyes Combined with Blepharoptosis after Levator Resection.
AB  - Background: This study aims to report the changes in sunken eyes combined with
      blepharoptosis after levator resection. Methods: Analysis involved 60 eyes from
      32 patients with sunken eyes combined with blepharoptosis. Advancement of the
      levator aponeurosis and the Muller's muscle complex (levator resection) was
      performed in these patients. Area of upper eyelid sulcus (AES) was defined as the
      area of the upper eyelid shadow. The digital images were converted to black and
      white using image-processing software (Adobe Photoshop), and the AES was
      calculated using ImageJ software. In addition, margin reflex distance, eyebrow
      height (EBH), and AES were measured before and 3 months after surgery to assess
      the changes in the eyelids. Results: Preoperative AES was significantly
      correlated to age (P < 0.0001; r = 0.8062). Sunken eyes were remarkably improved
      after levator resection in all patients. Mean margin reflex distance
      significantly increased, whereas mean EBH and mean AES significantly decreased at
      3 months after surgery (P < 0.0001). The AES change was significantly correlated
      to the EBH change (P < 0.0001; r = 0.5184). Conclusions: The principal aim of
      levator resection is to improve upper eyelid height and visual fields; however,
      this technique can alter the location of the eyebrow and upper orbital fat. The
      effects fill the hollowness of the upper eyelid and can remarkably improve sunken
      eyes.

PMID- 29632790
TI  - Use of Multidirectional Cranial Distraction Osteogenesis for Cranial Expansion in
      Syndromic Craniosynostosis.
AB  - Patients with syndromic craniosynostosis often require a large amount of cranial
      expansion to avoid intracranial hypertension, but the surgical procedure remains
      controversial. A patient of severe syndromic craniosynostosis with multiple bony
      defects and anomalous venous drainage at the occipital region was treated by
      multidirectional cranial distraction osteogenesis (MCDO) at the age of 8 months.
      Distraction started 5 days after surgery and ceased on postoperative day 16. The
      distraction devices were removed 27 days after completing distraction. After
      device removal, the increase of intracranial volume was 155 ml and the cephalic
      index was improved from 115.5 to 100.5. The resultant cranial shape was well
      maintained with minimal relapse at postoperative 9 months. In cases of syndromic
      craniosynostosis with multiple bony defects and/or anomalous venous drainage at
      the occipital region, expansion of the anterior cranium by MCDO is a viable
      alternative to conventional methods.

PMID- 29632791
TI  - A Simple and Inexpensive Postoperative Shield Dressing in Simultaneous
      Reconstruction of Nipple-Areola Complex.

PMID- 29632792
TI  - Qualitative and Quantitative Analysis of Smile Excursion in Facial Reanimation: A
      Systematic Review and Meta-analysis of 1- versus 2-stage Procedures.
AB  - Background: Free functional muscle transfer has become a common treatment
      modality for smile restoration in long-lasting facial paralysis, but the
      selection of surgical strategy between a 1-stage and a 2-stage procedure has
      remained a matter of debate. The aim of this study was to compare the
      quantitative and qualitative outcomes of smile excursion between 1-stage and 2
      stage free muscle transfers in the literature. Methods: A comprehensive review of
      the published literature between 1975 and end of January 2017 was conducted.
      Results: The abstracts or titles of 2,743 articles were screened. A total of 24
      articles met our inclusion criteria of performing a quantitative or qualitative
      evaluation of a free-functioning muscle transfer for smile restoration. For the
      purpose of meta-analysis, 7 articles providing quantitative data on a total of
      254 patients were included. When comparing muscle excursion between 1-stage and 2
      stage procedures, the average range of smile excursion was 11.5 mm versus 6.6 mm,
      respectively. For the purpose of systematic review, 17 articles were included.
      The result of the systematic review suggested a tendency toward superior
      functional results for the 1-stage procedure when comparing the quality of smile.
      Conclusions: The results of this review must be interpreted with great caution.
      Quantitative analysis suggests that 1-stage procedures produce better excursion
      than 2-stage procedures. Qualitative analysis suggests that 1-stage procedures
      might also produce superior results when based on excursion and symmetry alone,
      but these comparisons do not include one important variable dictating the quality
      of a smile-the spontaneity of the smile. The difficulty in comparing published
      results calls for a consensus classification system for facial palsy.

PMID- 29632793
TI  - Surgical Management of Massive Lower Extremity Lymphedema Secondary to
      Castleman's Disease.

PMID- 29632795
TI  - A Giant Neurovascular Lower Limb Fillet Flap Can Simultaneously Cover Pelvic and
      Abdominal Defects.
AB  - The first description of simultaneous pelvic and abdominal soft-tissue
      reconstruction with a giant lower limb fillet flap after hip exarticulation and
      open abdomen is presented. The unfortunate circumstances of a 67-year-old female
      patient are described leading to soft-tissue necrosis over a periprosthetic femur
      fracture and open abdomen after emergency implantation of an aortic bifemoral Y
      prosthesis because of thrombotic obliteration of the aortic bifurcation. After
      removal of the hip prosthesis, the neurovascular pedicled myocutaneous fillet
      flap of the entire left leg was raised and folded proximally at the level of the
      exarticulated joint of the hip and set into the pelvic and abdominal defect. A
      giant pedicled neurovascular myocutaneous fillet flap raised over the entire
      lower extremity is a safe, effective, durable, and sensation-preserving treatment
      to reconstruct combined pelvic and abdominal soft-tissue defects.

PMID- 29632794
TI  - Efficacy of Vancomycin-based Continuous Triple Antibiotic Irrigation in
      Immediate, Implant-based Breast Reconstruction.
AB  - Background: Single irrigation of the peri-implant space with a cefazolin-based
      triple antibiotic solution is a routine antibiotic prophylaxis measure during
      implant-based breast augmentation and reconstruction. Cefazolin, however, is less
      efficacious against resistant Staphylococcus species, which are the predominant
      bacterial species isolated from the peri-implant space. Vancomycin is effective
      against resistant Staphylococcus species and may be a more appropriate
      prophylactic agent. The availability of single-injection long-acting anesthetic
      agents allows the novel use of the elastomeric infusion pump for continuous
      irrigation of antibiotic solution into the peri-implant space. The efficacy of
      continuous irrigation with a vancomycin-based solution is evaluated here.
      Methods: Study patients (N = 163; group 1) who underwent immediate, direct-to
      implant breast reconstruction received continuous infusion of a vancomycin-based
      triple antibiotic solution. Patients also received a single injection of
      liposomal bupivacaine in the pectoralis major/minor muscles for pain control. A
      historic control group (N = 113; group II) received ropivacaine local anesthetic
      via the infusion pump and a single intraoperative irrigation of the peri-implant
      space with the vancomycin-based triple antibiotic solution. Incidence of
      postsurgical infection during the 6 weeks after surgery was compared between the
      groups. Results: Group I patients had a statistically significant lower incidence
      of infections (1.9%) than group II patients (6.4%) (P = 0.007). There were no
      vancomycin-related adverse effects. Conclusions: Continuous breast irrigation
      with a vancomycin-based triple antibiotic solution is a safe and effective
      accompaniment for immediate implant reconstruction. Use of intramuscular
      anesthetic injection for postoperative pain control allows the elastomeric
      infusion pump to be available for local tissue antibiotic irrigation.

PMID- 29632796
TI  - State of Plastic Surgery in Brazil.

PMID- 29632797
TI  - A New Pattern of the Sural Nerve Added to "Anatomy of the Sural Nerve: Cadaver
      Study and Literature Review".

PMID- 29632798
TI  - Monobloc Reconstruction of Dome, Medial Crura, and Columella with Gamma-Shaped
      Costal Cartilage Graft.
AB  - In severe nasal deformities, the original cartilages are removed, or they become
      unusable because of previous operations. Costal cartilage (CC) is one of the most
      important tools for the replacement of deficient nasal osteocartilaginous
      framework. In 4 secondary and 1 tertiary rhinoplasty cases with severe
      deformities of medial and lateral crura of the lower lateral cartilages, we have
      prepared a long strut graft from a CC and then split the graft tip 5-6 mm
      vertically into 2 equal halves to create a gamma (Upsilon)-shaped strut graft. We
      have sutured the base of this graft to the nasal spine and/or the bases of the
      medial crural remnants. Then, we have prepared lateral crural grafts and secured
      the grafts over lateral crural remnants. Then we curved the split tip winglets of
      the Upsilon-shaped strut graft to both sides and sutured them to lateral crural
      grafts in order to create a new dome. Splitting of the CC strut graft reduces the
      need for extensive suturing at the tip, obtains smoother contours and ensures
      graft economy, and provides an original and stable dome shape. The bending
      capacity of the CC is limited in middle-aged patients. Costal allografts from a
      young cadaver can be a good alternative. Upsilon-shaped costal crural graft is
      useful for medial crural and domal monobloc reconstruction in secondary and
      tertiary cases.

PMID- 29632799
TI  - Prepectoral Implant-Based Breast Reconstruction and Postmastectomy Radiotherapy:
      Short-Term Outcomes.
AB  - Background: Prosthetic breast reconstruction in the setting of radiotherapy is
      associated with poor outcomes. Until recently, prosthetic breast reconstruction
      was predominantly performed by placing the prosthesis in a subpectoral space.
      Placement of the prosthesis in a prepectoral space is currently emerging as a
      simpler, alternative approach to subpectoral placement. The impact of
      postmastectomy radiotherapy (PMRT) on prepectoral reconstruction has not yet been
      specifically assessed. This study compared the outcomes of patients who underwent
      immediate, direct-to-implant, or 2-staged, prepectoral breast reconstruction
      followed by PMRT with those from patients who did not receive PMRT. Methods:
      Patients with well-perfused skin flaps and without contraindications, including
      uncontrolled diabetes-mellitus, previous irradiation, and current tobacco use,
      were offered the prepectoral approach. Following implant or expander placement,
      patients underwent planned or unplanned radiotherapy. Complications after each
      stage of reconstruction were recorded. Results: Thirty-three patients underwent
      52 breast reconstructions via the prepectoral approach. Sixty-five percentage of
      the breasts were irradiated, including 21% after expander and 44% after implant
      placement. Patients were followed for a mean of 25.1 +/- 6.4 months. Complication
      rate in irradiated breasts was 5.9% (1 incidence of seroma and 1 incidence of
      wound dehiscence followed by expander removal) and 0% in nonirradiated breasts.
      Capsular contracture rate was 0% in both irradiated and nonirradiated breasts.
      Conclusions: Immediate implant-based prepectoral breast reconstruction followed
      by PMRT appears to be well tolerated, with no excess risk of adverse outcomes, at
      least in the short term. Longer follow-up is needed to better understand the risk
      of PMRT in prepectorally reconstructed breasts.

PMID- 29632800
TI  - Unilateral Straight Hair-A Symptom of Acquired Horner's Syndrome in a Neonate.
AB  - A multicystic tumor of the right neck was detected in a girl at 29 weeks of
      gestation by fetal ultrasound and magnetic resonance imaging (MRI). The baby was
      delivered by cesarean section at week 37 of gestation. The newborn adapted well,
      with minimal compromise of breathing and drinking. Postnatal ultrasound and MRI
      revealed a cervical lymphangioma measuring 60.5 * 60.6 * 41.2 mm. We performed
      subtotal resection of the tumor when the girl was 34 days. As a complication of
      surgical resection, the girl developed ipsilateral Horner's syndrome. In the
      postoperative period, her curled hair turned straight at the side of the head
      affected by Horner's syndrome. At the age of 2.5 years, ultrasonic imaging
      revealed the presence of three cysts measuring 3 mm in diameter each. Horner's
      syndrome had improved, and the texture of the girl's hair had become curly again
      on both sides.

PMID- 29632801
TI  - Cilostazol for the prevention of pneumonia: a systematic review.
AB  - Background: Pneumonia is a very common disease, especially among the elderly.
      Various drugs' preventive effects against pneumonia have been reported. The
      antiplatelet drug cilostazol is used to prevent pneumonia, but the robustness of
      its efficacy is unclear. This review estimates the effectiveness of cilostazol
      for preventing pneumonia in elderly individuals. Methods: The following databases
      were searched from the earliest record to January 2016, without language
      restriction (the secondary search was conducted on February 2017): MEDLINE,
      Cochrane Library, CINAHL, and Ichushi-Web. Studies were included if they were
      published randomized controlled trials investigating the preventive effect of
      cilostazol on pneumonia in the elderly. The outcome was the incidence of
      pneumonia. Results: Two trials were identified that met the search criteria (1423
      participants). Both trials compared cilostazol with no antiplatelet in patients
      with a history of cerebral infarction. A meta-analysis was not performed because
      of the small number of trials and the heterogeneity of the data. Both trials
      suggested that cilostazol reduced the incidence of pneumonia (risk ratio [RR]
      0.40; 95% confidence interval [CI] 0.22-0.73 in one trial, RR 0.20; 95% CI 0.06
      0.69 in the other) and the recurrence of cerebral infarction (0.43; 0.21-0.90,
      0.53; 0.34-0.81, respectively). The quality of evidence provided by the trials
      was very low, mainly because of the high risk of bias. Conclusions: It is
      difficult to draw conclusions on the basis of two trials. Moreover, in the two
      trials, cilostazol could have reduced the incidence of pneumonia via a reduction
      of the recurrence of cerebral infarction, which suggests that other antiplatelets
      could also have the same effects. Stronger evidence is required from large trials
      assessing the effectiveness of cilostazol for the prevention of pneumonia. Trial
      registration: PROSPERO (CRD42016036724).

PMID- 29632802
TI  - Environment perception and leisure-time physical activity in Portuguese high
      school students.
AB  - This study aims to analyze the association between perceived environmental
      factors and leisure-time physical activity (PA) among adolescents of both
      genders. Data were collected in autumn of 2011 from 866 adolescents (412 girls
      and 454 boys) 12- to 18-years-old, from four Portuguese cities. Perception of
      environmental factors was assessed by Assessing Levels of Physical Activity and
      Fitness (ALPHA) questionnaire (Spittaels et al., 2010, IJBNPA). PA was assessed
      by a questionnaire that evaluated PA during leisure-time and participants were
      assigned into the following categories: sedentary; low active; moderate active;
      and very active. Boys presented higher levels of structured PA, frequency and
      intensity of PA, and level of sport competition than girls (p < 0.001). Distance
      to local facilities (p = 0.001 for girls; p < 0.001 for boys) and home
      environment (p = 0.004 for girls; p = 0.015 for boys) were negatively associated
      with PA. Total, cycling and walking infrastructures (p < 0.001), as well as
      cycling and walking network (p = 0.049) and connectivity (p = 0.034) showed a
      positive association with PA in boys. Analysis of variance showed significant
      differences between girls' PA regarding aesthetics (p = 0.013), study environment
      (p = 0.023), home environment (p = 0.014) and whether it is pleasant or not (p =
      0.023). Differences between boys' PA were observed for distance to local
      facilities (p = 0.003), total, cycling and walking infrastructures (p < 0.001)
      and home environment (p = 0.002). This study results support that some
      environmental factors are associated with adolescents' PA levels, with relevant
      differences between genders. Therefore, these gender differences must be taken
      into account, in order to increase levels of PA in Portuguese youth, especially
      in girls.

PMID- 29632803
TI  - Monitoring how changes in pedagogical practices have improved student interest
      and performance for an introductory biochemistry course.
AB  - This study describes feedback on the effects of changes introduced in our
      teaching practices for an introductory biochemistry course in the Life Sciences
      curriculum. Students on this course have diverse educational qualifications and
      are taught in large learning groups, creating challenges for the management of
      individual learning. We used the constructive alignment principle, refining the
      learning contract and re-drafting the teaching program to introduce active
      learning and an organization of activities that promotes the participation of all
      the students and helps their understanding. We also created teaching resources
      available through the university virtual work environment. Our research aimed to
      measure the effects of those changes on the students' success. Monitoring of the
      student performance showed a continuous increase in the percentage of students
      who passed the course, from 2.13% to 33.5% in 4 years. Analysis of student
      perceptions highlighted that the teaching methodology was greatly appreciated by
      the students, whose attendance also improved. The recent introduction of clickers
      questions constituted a complementary leverage. The active involvement of the
      students and better results for summative assessments are altogether a strong
      motivation for teaching staff to continue to make improvements.

PMID- 29632804
TI  - MicroRNA profiling during directed differentiation of cortical interneurons from
      human-induced pluripotent stem cells.
AB  - Induced pluripotent stem cells (iPSCs) are useful for modeling neuron development
      and related diseases. Cortical interneurons are essential players in
      neuropsychiatric diseases such as autism. miRNAs are a class of pivotal
      regulators in neural differentiation. Using a previously established model of
      cortical interneuron differentiation from human embryonic stem cells, we profiled
      miRNAs involved in differentiation from human iPSCs. A number of miRNAs were
      modulated in the differentiation process. This study captured the temporal in
      vitro neurogenesis from iPSCs to mature cortical interneurons. The specific
      miRNAs identified at each stage of differentiation are of potential use for drug
      discovery and prospective clinical applications.

PMID- 29632805
TI  - Inhibition of endothelial nitric oxide synthase in cholangiocarcinoma cell lines 
      a new strategy for therapy.
AB  - The isoform of nitric oxide synthase (NOS) found in endothelial cells (eNOS)
      plays a crucial role in vasodilation. We recently reported the activation of eNOS
      in cholangiocarcinoma (CCA) tissues and cell lines. Moreover, we also reported
      that the abundance of eNOS and phosphorylated eNOS (p-eNOS), as well as its
      upstream regulator proteins, is significantly associated with the metastatic
      status of CCA patients. However, the function of eNOS in CCA progression has not
      been addressed. Therefore, the present study aimed to investigate the function of
      eNOS involved in the migration and invasion ability of CCA cell lines. The
      results reveal that eNOS activation significantly increases migration and
      invasion ability of CCA cells via the up-regulation of phosphorylated vasodilator
      stimulated protein (p-VASP). A combination treatment with recombinant human
      vascular endothelial growth factor C and eNOS inhibitor (Nomega-nitro-l-arginine
      methyl ester hydrochloride) resulted in the down-regulation of p-VASP, as well as
      a decreased migration and invasion ability of the CCA cell line. Thus, this work
      suggests that eNOS can serve as an attractive target to inhibit the progression
      of CCA.

PMID- 29632806
TI  - A small-molecule PAI-1 inhibitor prevents bone loss by stimulating bone formation
      in a murine estrogen deficiency-induced osteoporosis model.
AB  - Osteoporosis is a progressive bone disease caused by an imbalance between bone
      resorption and formation. Recently, plasminogen activator inhibitor-1 (PAI-1) was
      shown to play an important role in bone metabolism using PAI-1-deficient mice. In
      this study, we evaluated the therapeutic benefits of novel, orally available
      small-molecule PAI-1 inhibitor (iPAI-1) in an estrogen deficiency-induced
      osteoporosis model. Eight-week-old C57BL/6J female mice were divided into three
      groups: a sham + vehicle (Sham), ovariectomy + vehicle (OVX + v), and OVX + iPAI
      1 (OVX + i) group. iPAI-1 was administered orally each day for 6 weeks starting
      the day after the operation. Six weeks of iPAI-1 treatment prevented OVX-induced
      trabecular bone loss in both the femoral bone and lumbar spine. Bone formation
      activity was significantly higher in the OVX + i group than in the OVX + v and
      Sham groups. Unexpectedly, OVX-induced osteoclastogenesis was partially, but
      significantly reduced. Fluorescence-activated cell sorting analyses indicated
      that the number of bone marrow stromal cells was higher in the OVX + i group than
      that in the OVX + v group. A colony-forming unit-osteoblast assay indicated
      enhanced mineralized nodule formation activity in bone marrow cells isolated from
      iPAI-1-treated animals. Bone marrow ablation analysis indicated that the
      remodeled trabecular bone volume was significantly higher in the iPAI-1-treated
      group than that in the control group. In conclusion, our results suggest PAI-1
      blockade via a small-molecule inhibitor is a new therapeutic approach for the
      anabolic treatment of postmenopausal osteoporosis.

PMID- 29632807
TI  - PSMD7 downregulation induces apoptosis and suppresses tumorigenesis of esophageal
      squamous cell carcinoma via the mTOR/p70S6K pathway.
AB  - PSMD7, a 19S proteasome subunit, is overexpressed in most carcinoma cells. It
      forms a dimer with PSMD14 that functions in the removal of attached ubiquitin
      chain. However, there is little knowledge about the cellular mechanism of PSMD7
      and its exact biological function, especially in cancer cells. In this study, we
      explored the role of PSMD7 in proliferation, cell cycle, apoptosis, and
      proteasomal proteolysis in the esophageal squamous cell carcinoma (ESCC) cell
      line EC9706. Our results showed that PSMD7 was highly expressed in ESCC cells.
      Downregulation of PSMD7 by lentivirus-mediated shRNA led to decreased
      proliferation, increased cell apoptosis, and reduced proteasomal function.
      Notably, lower expression level of mTOR and p70S6K and suppressed activity of
      mTOR/p70S6K pathway were detected after PSMD7 downregulation. By contrast,
      increased expression of p-mTORSer2448 and p-p70S6KThr421/Ser424 was discovered
      upon PSMD7 overexpression in Het-1A cells. Furthermore, PSMD7 downregulation
      contributed to decelerated tumor growth, inhibition of proteasomal function,
      induced cell apoptosis and attenuated activity of mTOR/p70S6K pathway in vivo.
      These findings suggest that PSMD7 and the mTOR/p70S6K pathway may be a promising
      candidate for developing therapies for ESCC.

PMID- 29632808
TI  - Profiling expression of coding genes, long noncoding RNA, and circular RNA in
      lung adenocarcinoma by ribosomal RNA-depleted RNA sequencing.
AB  - : Noncoding RNA play important roles in various biological processes and
      diseases, including cancer. The expression profile of circular RNA (circRNA) has
      not been systematically investigated in lung adenocarcinoma (LUAD). In this
      study, we performed genomewide transcriptome profiling of coding genes, long
      noncoding RNA (lncRNA), and circRNA in paired LUAD and nontumor tissues by
      ribosomal RNA-depleted RNA sequencing. The detected reads were first mapped to
      the human genome to analyze expression of coding genes and lncRNA, while the
      unmapped reads were subjected to a circRNA prediction algorithm to identify
      circRNA candidates. We identified 1282 differentially expressed coding genes in
      LUAD. Expression of 19 023 lncRNA was detected, of which 244 lncRNAs were
      differentially expressed in LUAD. AFAP1-AS1, BLACAT1, LOC101928245, and FENDRR
      were most differentially expressed lncRNAs in LUAD. Also identified were 9340
      circRNA candidates with >= 2 backspliced, including 3590 novel circRNA
      transcripts. The median length of circRNA was ~ 530 nt. CircRNA are often of low
      abundance, and more than half of circRNAs we identified had < 10 reads. Agarose
      electrophoresis and Sanger sequencing were used to confirm that four candidate
      circRNA were truly circular. Our results characterized the expression profile of
      coding genes, lncRNA, and circRNA in LUAD; 9340 circRNAs were detected,
      demonstrating that circRNA are widely expressed in LUAD. Database: The raw RNA
      sequencing data have been submitted to Gene Expression Omnibus (GEO) database and
      can be accessed with the ID GEO:
      http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE104854.

PMID- 29632809
TI  - Salivary proteome profiling of oral squamous cell carcinoma in a Hungarian
      population.
AB  - Oral squamous cell carcinoma (OSCC) is the seventh most common malignancy and the
      ninth most frequent cause of cancer death in Europe. Within Europe, Hungary has
      one of the highest rates of OSCC incidence and mortality. Thus, there is an
      urgent need to improve early detection. Saliva, as a readily available body
      fluid, became an increasingly important substance for the detection of biomarkers
      for many diseases. Different research groups have identified salivary biomarkers
      specific for OSCC for different countries. In this study, saliva samples of
      Hungarian patients with OSCC were studied to discover disease-specific and
      perhaps region-specific biomarkers. LC-mass spectrometry (MS)/MS analysis on a
      linear ion trap-Orbitrap mass spectrometer was used for qualitative and
      quantitative salivary protein profiling. More than 500 proteins were identified
      from saliva by shotgun proteomics. The up- and downregulated proteins in the
      saliva of patients with OSCC highlighted the importance of protein-protein
      interaction networks involving the immune system and proteolysis in disease
      development. Two potential biomarkers from our shotgun analysis and a third
      candidate reported earlier by a Taiwanese group were further examined by ELISA on
      a larger reference set of samples. Resistin, a biomarker reported in Taiwan but
      not validated in our study, highlights the necessity of application of
      standardized analysis methods in different ethnic or geographical populations to
      identify biomarkers with sufficient specificity and sensitivity.

PMID- 29632810
TI  - Tropomyosin isoforms have specific effects on the transcriptome of
      undifferentiated and differentiated B35 neuroblastoma cells.
AB  - : Tropomyosins, a family of actin-associated proteins, bestow actin filaments
      with distinct biochemical and physical properties which are important for
      determining cell shape and regulating many cellular processes in eukaryotic
      cells. Here, we used RNA-seq to investigate the effect of four tropomyosin
      isoforms on gene expression in undifferentiated and differentiated rat B35
      neuroblastoma cells. In undifferentiated cells, overexpression of tropomyosin
      isoforms Tpm1.12, Tpm2.1, Tpm3.1, and Tpm4.2 differentially regulates a vast
      number of genes, clustering into several gene ontology terms. In differentiated
      cells, tropomyosin overexpression exerts a much weaker influence on overall gene
      expression. Our findings are particularly compelling because they demonstrate
      that tropomyosin-dependent changes are attenuated once the cells are induced to
      follow a defined path of differentiation. Database: Sequence data for public
      availability are deposited in the European Nucleotide Archive under the accession
      number PRJEB24136.

PMID- 29632811
TI  - Inhibition of DNA methyltransferase leads to increased genomic 5
      hydroxymethylcytosine levels in hematopoietic cells.
AB  - 5-Hydroxymethylcytosine (5hmC) is produced from 5-methylcytosine (5mC) by Ten
      eleven translocation (TET) dioxygenases. The epigenetic modification 5hmC has
      crucial roles in both cellular development and differentiation. The 5hmC level is
      particularly high in the brain. While 5mC is generally associated with gene
      silencing/reduced expression, 5hmC is a more permissive epigenetic mark. To
      understand its physiological function, an easy and accurate quantification method
      is required. Here, we have developed a novel LC-MS/MS-based approach to quantify
      both genomic 5mC and 5hmC contents. The method is based on the liberation of
      nucleobases by formic acid. Applying this method, we characterized the levels of
      DNA methylation and hydroxymethylation in mouse brain and liver, primary
      hepatocytes, and various cell lines. Using this approach, we confirm that the
      treatment of different cell lines with the DNA methyltransferase inhibitor 5-aza
      2'-deoxycytidine leads to a decrease in 5mC content. This decrease was
      accompanied by an increase in 5hmC levels in cell lines of hematopoietic origin.
      Finally, we showed that ascorbate elevates the levels of 5hmC and augments the
      effect of 5-aza-2'-deoxycytidine without significantly influencing 5mC levels.

PMID- 29632812
TI  - Identification of NADPH oxidase family members associated with cold stress in
      strawberry.
AB  - NADPH oxidase is encoded by a small gene family (Respiratory burst oxidase
      homologs, Rbohs) and plays an important role in regulating various biological
      processes. However, little information about this gene family is currently
      available for strawberry. In this study, a total of seven Rboh genes were
      identified from strawberry through genomewide analysis. Gene structure analysis
      showed the number of exons ranged from 10 to 23, implying that this variation
      occurred in FvRboh genes by the insertion and distribution of introns; the order
      and approximate size of exons were relatively conserved. FvRbohC was predicted to
      localize to the thylakoid membrane of the chloroplast, while other members were
      computed to localize to the plasma membrane, indicating different functions.
      Amino acid sequence alignment, conserved domain, and motif analysis showed that
      all identified FvRbohs had typical features of plant Rbohs. Phylogenetic analysis
      of Rbohs from strawberry, grape, Arabidopsis, and rice suggested that the FvRbohs
      could be divided into five subgroups and showed a closer relationship with those
      from grape and Arabidopsis than those from rice. The expression patterns of
      FvRboh genes in root, stem, leaf, flower, and fruit revealed robust tissue
      specificity. The expression levels of FvRbohA and FvRbohD were quickly induced by
      cold stress, followed by an increase in NADPH oxidase activity, leading to O2-
      accumulation and triggering the antioxidant reaction by the transient increases
      in SOD activity. This suggested these two genes may be involved in cold stress
      and defense responses in strawberry.

PMID- 29632813
TI  - Kinetics and inhibition studies of the L205R mutant of cAMP-dependent protein
      kinase involved in Cushing's syndrome.
AB  - Overproduction of cortisol by the hypothalamus-pituitary-adrenal hormone system
      results in the clinical disorder known as Cushing's syndrome. Genomics studies
      have identified a key mutation (L205R) in the alpha-isoform of the catalytic
      subunit of cAMP-dependent protein kinase (PKACalpha) in adrenal adenomas of
      patients with adrenocorticotropic hormone-independent Cushing's syndrome. Here,
      we conducted kinetics and inhibition studies on the L205R-PKACalpha mutant. We
      have found that the L205R mutation affects the kinetics of both Kemptide and ATP
      as substrates, decreasing the catalytic efficiency (kcat/KM) for each substrate
      by 12-fold and 4.5-fold, respectively. We have also determined the IC 50 and Ki
      for the peptide substrate-competitive inhibitor PKI(5-24) and the ATP-competitive
      inhibitor H89. The L205R mutation had no effect on the potency of H89, but causes
      a > 250-fold loss in potency for PKI(5-24). Collectively, these data provide
      insights for the development of L205R-PKACalpha inhibitors as potential
      therapeutics.

PMID- 29632814
TI  - The TNF-alpha-induced expression of miR-130b protects cervical cancer cells from
      the cytotoxicity of TNF-alpha.
AB  - Tumour necrosis factor alpha (TNF-alpha) is a multifunctional cytokine and has
      the capacity both to promote cell growth and to kill tumour cells by inducing
      cell apoptosis. However, many tumour cells develop resistance to the toxic
      effects of TNF-alpha. Thus, understanding the mechanism underlying the resistance
      of tumours to TNF-alpha toxicity and finding ways to overcome this resistance are
      urgently needed. In this study, we discovered that two cervical cancer cell
      lines, Hela and Siha, showed null responses to TNF-alpha cytotoxicity. However,
      in these cell lines, TNF-alpha stimulation promoted the expression of miR-130b
      and downregulated the expression of PTEN gene, which encodes a dual-specificity
      phosphatase that acts as a tumour suppressor. Blockade of miR-130b function or
      overexpression of PTEN gene sensitized cells to TNF-alpha cytotoxicity.
      Regression analyses revealed that there were reverse relationships between the
      cellular levels of miR-130b and PTEN mRNA in cervical cancer cells. Gain- and
      loss-of-function assays demonstrated that there were causal relationships between
      the increase in miR-130b levels and the reduction in PTEN mRNA or PTEN protein
      levels. In silico analysis revealed that there were two miR-130b target sites
      within the 3'UTR of PTEN mRNA and experimental evidences demonstrated that miR
      130b repressed the expression of PTEN gene by binding directly to the 3'UTR of
      PTEN mRNA. These data suggest miR-130b expression as a target to be inhibited to
      make tumour cells more sensitive to the toxic impact of TNF-alpha.

PMID- 29632816
TI  - The anti-human cytomegalovirus drug tricin inhibits cyclin-dependent kinase 9.
AB  - 4',5,7-trihydroxy-3',5'-dimethoxyflavone (tricin), derived from Sasa albo
      marginata, has been reported to suppress significantly human cytomegalovirus
      (HCMV) replication in human embryonic lung (HEL) fibroblast cells. However, the
      target protein of tricin remains unclear. This study focused on the anti-HCMV
      activity of tricin in terms of its binding affinity to cyclin-dependent kinase 9
      (CDK9). A molecular docking study predicted that tricin binds well to the ATP
      binding site of CDK9. Experimental measurements then revealed that tricin
      inhibits the kinase activity of CDK9 and affects the phosphorylation of the
      carboxy-terminal domain of RNA polymerase II. Based on these results, we conclude
      that CDK9 is one of the target proteins of tricin. We also found that tricin
      possesses anti-HCMV activity with no cytotoxicity against HEL cells.

PMID- 29632815
TI  - Characterization of thiol-based redox modifications of Brassica napusSNF1-related
      protein kinase 2.6-2C.
AB  - Sucrose nonfermenting 1-related protein kinase 2.6 (SnRK2.6), also known as Open
      Stomata 1 (OST1) in Arabidopsis thaliana, plays a pivotal role in abscisic acid
      (ABA)-mediated stomatal closure. Four SnRK2.6 paralogs were identified in the
      Brassica napus genome in our previous work. Here we studied one of the paralogs,
      BnSnRK2.6-2C, which was transcriptionally induced by ABA in guard cells.
      Recombinant BnSnRK2.6-2C exhibited autophosphorylation activity and its
      phosphorylation sites were mapped. The autophosphorylation activity was inhibited
      by S-nitrosoglutathione (GSNO) and by oxidized glutathione (GSSG), and the
      inhibition was reversed by reductants. Using monobromobimane (mBBr) labeling, we
      demonstrated a dose-dependent modification of BnSnRK2.6-2C by GSNO. Furthermore,
      mass spectrometry analysis revealed previously uncharacterized thiol-based
      modifications including glutathionylation and sulfonic acid formation. Of the six
      cysteine residues in BnSnRK2.6-2C, C159 was found to have different types of
      thiol modifications, suggesting its high redox sensitivity and versatility. In
      addition, mBBr labeling on tyrosine residues was identified. Collectively, these
      data provide detailed biochemical characterization of redox-induced modifications
      and changes of the BnSnRK2.6-2C activity.

PMID- 29632817
TI  - Disruption of the mouse Slc39a14 gene encoding zinc transporter ZIP14 is
      associated with decreased bone mass, likely caused by enhanced bone resorption.
AB  - Osteoclasts are bone-resorbing cells that play an essential role in maintaining
      bone homeostasis. Zinc (Zn) has been reported to inhibit osteoclast-mediated bone
      resorption, but the mechanism of this action has not been clarified. Zn
      homeostasis is tightly controlled by the coordinated actions of many Zn
      transporters. The Zn transporter ZIP14/Slc39a14 is involved in various
      physiological functions; hence, Zip14-knockout (KO) mice exhibit multiple
      phenotypes. In this study, we thoroughly investigated the bone phenotypes of
      Zip14-KO mice, demonstrating that the KO mice exhibited osteopenia in both
      trabecular and cortical bones. In Zip14-KO mice, bone resorption was increased,
      whereas the bone formation rate was unchanged. Zip14 mRNA was expressed in normal
      osteoclasts both in vivo and in vitro, but receptor activator of NF-kappaB ligand
      (RANKL)-induced osteoclastogenesis was not impaired in bone marrow-derived
      macrophages prepared from Zip14-KO mice. These results suggest that ZIP14
      regulates bone homeostasis by inhibiting bore resorption and that in Zip14-KO
      mice, bone resorption is increased due to the elimination of this inhibitory
      regulation. Further studies are necessary to conclude whether the enhancement of
      bone resorption in Zip14-KO mice is due to a cell-autonomous or a non-cell
      autonomous osteoclast defect.

PMID- 29632818
TI  - Obesity-associated glomerular inflammation increases albuminuria without renal
      histological changes.
AB  - Obesity is one of risk factors for chronic kidney disease (CKD), but the precise
      mechanism involved is unclear. This study characterizes the effect of obesity
      induced glomerular inflammation, oxidative stress, and albuminuria in obese rats.
      Glomerular samples were collected from fatty (ZF) and lean (ZL) Zucker rats.
      After 2 months of feeding, body weight and albuminuria were significantly
      increased in ZF rats when compared to ZL rats. Expression of the inflammatory
      markers TNF-alpha and CCR2 was significantly increased in the glomeruli of ZF
      rats. However, expression of IL-6 mRNA was not increased. Analysis of renal
      pathology showed no glomerular expansion. As inflammatory and oxidative stress
      markers are associated with NF-kappaB, we evaluated whether NF-kappaB activation
      was increased in the glomeruli of mice on a high-fat diet. Immunohistochemistry
      showed increased NF-kappaB activation in the glomeruli when transgenic mice
      overexpressing an NF-kappaB-dependent enhanced green fluorescent protein were fed
      with a high-fat diet. These results suggest that obesity of only 2 months
      duration can cause albuminuria, due to increased inflammation or oxidative
      stress, but may not be long enough to develop renal pathological changes.

PMID- 29632819
TI  - Helicobacter pylori induces somatic mutations in TP53 via overexpression of CHAC1
      in infected gastric epithelial cells.
AB  - Infection with Helicobacter pylori is known to decrease the level of glutathione
      in gastric epithelial cells and increase the production of reactive oxygen
      species (ROS), which can lead to DNA damage and the development of gastric
      cancer. Cation transport regulator 1 (CHAC1) has gamma-glutamylcyclotransferase
      activity that degrades glutathione. We found that cagA-positive H. pylori
      infection triggered CHAC1 overexpression in human gastric epithelial (AGS) cells
      leading to glutathione degradation and the accumulation of ROS. Nucleotide
      alterations in the TP53 tumour suppressor gene were induced in AGS cells
      overexpressing CHAC1, whereas no mutations were detected in cells overexpressing
      a catalytically inactive mutant of CHAC1. A high frequency of TP53 mutations
      occurred in H. pylori-infected AGS cells, but this was prevented in cells
      transfected with CHAC1 siRNA. These findings indicate that H. pylori-mediated
      CHAC1 overexpression degrades intracellular glutathione, allowing the
      accumulation of ROS which subsequently causes mutations that could contribute to
      the development of gastric cancer.

PMID- 29632820
TI  - Crystal structures of FMN-bound and FMN-free forms of dihydroorotate
      dehydrogenase from Trypanosoma brucei.
AB  - Dihydroorotate dehydrogenase (DHODH) is a flavin-binding enzyme essential for
      pyrimidine biosynthesis, which converts dihydroorotate to orotate. Three
      dimensional structures of cytosolic DHODH of parasitic protozoa are of interest
      in drug discovery for neglected tropical diseases, especially because these
      enzymes possess significantly different structural and functional properties from
      the membrane-associated human enzyme. The existing crystal structures of the
      flavin mononucleotide (FMN)-bound DHODHs reveal a number of interactions
      stabilizing FMN. However, to understand the binding mechanism correctly, it is
      necessary to compare the structures of the FMN-bound and FMN-free forms, because
      the protein moiety of the former is not necessarily the same as the latter. Here,
      we prepared the FMN-free DHODH of Trypanosoma brucei using an Escherichia coli
      overexpression system. Although this apoform lacks enzymatic activity, simple
      incubation with FMN activated the enzyme. It was stable enough to be
      crystallized, enabling us to determine its structure by X-ray crystallography at
      1.6 A resolution. We also determined the FMN-bound form at 1.8 A resolution.
      Although the two structures have essentially the same scaffold, we observed
      flipping of a peptide-bond plane in the vicinity of the FMN-binding site,
      accompanied by an alternative hydrogen-bonding pattern. Comparisons of B factors
      of the protein main chain revealed that binding of FMN decreased flexibility of
      most of the residues at the FMN-binding site, but increased flexibility of a lid
      like loop structure over the active center. This increase was ascribed to a
      conformational change in an FMN-contacting residue, Asn195, which induced a
      rearrangement of a hydrogen-bond network of the residues comprising the lid.

PMID- 29632821
TI  - Cytoprotective activity of mitochondrial uncoupling protein-2 in lung and spleen.
AB  - Mitochondrial uncoupling protein-2 (UCP2) mediates free fatty acid (FA)-dependent
      H+ translocation across the inner mitochondrial membrane (IMM), which leads to
      acceleration of respiration and suppression of mitochondrial superoxide
      formation. Redox-activated mitochondrial phospholipase A2 (mt-iPLA2gamma) cleaves
      FAs from the IMM and has been shown to acts in synergy with UCP2. Here, we tested
      the mechanism of mt-iPLA2gamma-dependent UCP2-mediated antioxidant protection
      using lipopolysaccharide (LPS)-induced pro-inflammatory and pro-oxidative
      responses and their acute influence on the overall oxidative stress reflected by
      protein carbonylation in murine lung and spleen mitochondria and tissue
      homogenates. We provided challenges either by blocking the mt-iPLA 2gamma
      function by the selective inhibitor R-bromoenol lactone (R-BEL) or by removing
      UCP2 by genetic ablation. We found that the basal levels of protein carbonyls in
      lung and spleen tissues and isolated mitochondria were higher in UCP2-knockout
      mice relative to the wild-type (wt) controls. The administration of R-BEL
      increased protein carbonyl levels in wt but not in UCP2-knockout (UCP2-KO) mice.
      LPS further increased the protein carbonyl levels in UCP2-KO mice, which
      correlated with protein carbonyl levels determined in wt mice treated with R-BEL.
      These results are consistent with the UCP2/mt-iPLA 2gamma antioxidant mechanisms
      in these tissues and support the existence of UCP2-synergic mt-iPLA 2gamma
      dependent cytoprotective mechanism in vivo.

PMID- 29632822
TI  - ADAM17 is essential for ectodomain shedding of the EGF-receptor ligand
      amphiregulin.
AB  - The epidermal growth factor (EGF)-receptor ligand amphiregulin (AREG) is a potent
      growth factor implicated in proliferative skin diseases and in primary and
      metastatic epithelial cancers. AREG, synthesized as a propeptide, requires
      conversion to an active peptide by metalloproteases by a process known as
      ectodomain shedding. Although (ADAM17) a disintegrin and metalloprotease 17 is a
      key sheddase of AREG, ADAM8-, ADAM15-, and batimastat (broad metalloprotease
      inhibitor)-sensitive metalloproteases have also been implicated in AREG shedding.
      In the present study, using a curly bare (Rhbdf2cub ) mouse model that shows loss
      of-hair, enlarged sebaceous gland, and rapid cutaneous wound-healing phenotypes
      mediated by enhanced Areg mRNA and protein levels, we sought to identify the
      principal ectodomain sheddase of AREG. To this end, we generated Rhbdf2cub mice
      lacking ADAM17 specifically in the skin and examined the above phenotypes of
      Rhbdf2cub mice. We find that ADAM17 deficiency in the skin of Rhbdf2cub mice
      restores a full hair coat, prevents sebaceous gland enlargement, and impairs the
      rapid wound-healing phenotype observed in Rhbdf2cub mice. Furthermore, in vitro,
      stimulated shedding of AREG is abolished in Rhbdf2cub mouse embryonic
      keratinocytes lacking ADAM17. Thus, our data support previous findings
      demonstrating that ADAM17 is the major ectodomain sheddase of AREG.

PMID- 29632823
TI  - MucR binds multiple target sites in the promoter of its own gene and is a heat
      stable protein: Is MucR a H-NS-like protein?
AB  - The protein MucR from Brucella spp. is involved in the expression regulation of
      genes necessary for host interaction and infection. MucR is a member of the
      Ros/MucR family, which comprises prokaryotic zinc-finger proteins and includes
      Ros from Agrobacterium tumefaciens and the Ml proteins from Mesorhizobium loti.
      MucR from Brucella spp. can regulate the expression of virulence genes and
      repress its own gene expression. Despite the well-known role played by MucR in
      the repression of its own gene, no target sequence has yet been identified in the
      mucR promoter gene. In this study, we provide the first evidence that MucR from
      Brucella abortus binds more than one target site in the promoter region of its
      own gene, suggesting a molecular mechanism by which this protein represses its
      own expression. Furthermore, a circular dichroism analysis reveals that MucR is a
      heat-stable protein. Overall, the results of this study suggest that MucR might
      resemble a H-NS protein.

PMID- 29632824
TI  - Citrulline counteracts overweight- and aging-related effects on adiponectin and
      leptin gene expression in rat white adipose tissue.
AB  - We recently demonstrated that citrulline (CIT) reduced the expression of
      inflammatory genes in cultured explants from retroperitoneal (RET) white adipose
      tissue (WAT) from young (2-4 months) but not old (25 months) rats. Here we show
      that in RET WAT from old rats and high-fat-diet-fed (HFD) young rats, the basal
      expression of the leptin gene was increased (275-345%) whereas that of the
      adiponectin gene was decreased (48-60%), when compared to those from control-diet
      fed (CD) young rats. We show also that in RET WAT from old rats, a diet
      supplemented with CIT for 3 months reduced macrophage (F4/80, CD68) and
      inflammation (interleukin-6, tumor necrosis factor-alpha) marker genes 23-97%.
      CIT supplementation lowered leptin mRNA 62% and increased adiponectin mRNA 232%.
      In cultured explants of RET WAT from 4 month-old CD, 4 month-old HFD and 25-month
      old CD rats, the exposure to 2.5 mmol/L CIT for 24 h up-regulated adiponectin
      gene expression 151%, 362% and 216% respectively. In contrast, leptin gene
      expression was down-regulated 66% selectively in CIT-treated explants from 25
      month-old CD rats. These results further support the proposed beneficial effect
      of CIT to counteract the deleterious effects of aging and overweight on the
      metabolic, inflammatory and endocrine functions of WAT.

PMID- 29632825
TI  - Albumin removal from human fibrinogen preparations for manufacturing human fibrin
      based biomaterials.
AB  - Commercially available two component human fibrin sealants are commonly used to
      manufacture human fibrin-based biomaterials. However, this method is costly and
      allows little room for further tuning of the biomaterial. Human fibrinogen
      solutions offer a more cost-effective and versatile alternative to manufacture
      human fibrin-based biomaterials. Yet, human fibrinogen is highly unstable and
      contains certain impurities like human albumin. Within the context of
      biomaterials and tissue engineering we offer a simple yet novel solution based on
      classical biochemical techniques to significantly reduce albumin in human
      fibrinogen solutions. This method can be used for various tissue engineering and
      biomedical applications as an initial step in the manufacturing of human fibrin
      based biomaterials to optimise their regenerative application.

PMID- 29632826
TI  - Palmitoyl-ceramide accumulation with necrotic cell death in A549 cells, followed
      by a steep increase in sphinganine content.
AB  - Ceramides (Cers) have recently been identified as key signaling molecules that
      mediate biological functions such as cell growth, differentiation, senescence,
      apoptosis, and autophagy. However, the functions of Cer accumulation in necrotic
      cell death remain unknown. The aim of this study was to clarify the relationship
      between Cer accumulation with inhibition of the conversion pathway of Cer and
      concomitant necrotic cell death. In order to minimize the effect of apoptosis
      against necrotic cell death, A549 cells having the inhibiting effect of caspase 9
      by survivin were used in this study. Consequently, Cer accumulation in A549 cells
      would likely be associated with a pathway other than the mitochondrial caspase
      dependent pathway of apoptosis. Here, we showed that the dual addition of a
      glucosyl-Cer synthase inhibitor and a ceramidase inhibitor to A549 cell culture
      induced palmitoyl-Cer accumulation with Cer synthase 5 expression and necrotic
      cell death with lysosomal rupture together with leakage of cathepsin
      B/alkalization after 2-3 h, although it is unknown in this study whether the
      necrotic cell death was caused by the lysosomal rupture. This Cer accumulation
      was followed by a steep increase in sphinganine base levels via the activation of
      serine palmitoyltransferase activity brought about by the increase in palmitoyl
      coenzyme A concentration as a substrate after 5-6 h. The increase in palmitoyl
      coenzyme A concentration was achieved by activation of the fatty acid synthetic
      pathway from acetyl coenzyme A.

PMID- 29632827
TI  - Proline substitutions in a Mip-like peptidyl-prolyl cis-trans isomerase severely
      affect its structure, stability, shape and activity.
AB  - FKBP22, an Escherichia coli-specific peptidyl-prolyl cis-trans isomerase, shows
      substantial homology with the Mip-like virulence factors. Mip-like proteins are
      homodimeric and possess a V-shaped conformation. Their N-terminal domains form
      dimers, whereas their C-terminal domains bind protein/peptide substrates and
      distinct inhibitors such as rapamycin and FK506. Interestingly, the two domains
      of the Mip-like proteins are separated by a lengthy, protease-susceptible alpha
      helix. To delineate the structural requirement of this domain-connecting region
      in Mip-like proteins, we have investigated a recombinant FKBP22 (rFKBP22) and its
      three point mutants I65P, V72P and A82P using different probes. Each mutant
      harbors a Pro substitution mutation at a distinct location in the hinge region.
      We report that the three mutants are not only different from each other but also
      different from rFKBP22 in structure and activity. Unlike rFKBP22, the three
      mutants were unfolded by a non-two state mechanism in the presence of urea. In
      addition, the stabilities of the mutants, particularly I65P and V72P, differed
      considerably from that of rFKBP22. Conversely, the rapamycin binding affinity of
      no mutant was different from that of rFKBP22. Of the mutants, I65P showed the
      highest levels of structural/functional loss and dissociated partly in solution.
      Our computational study indicated a severe collapse of the V-shape in I65P due to
      the anomalous movement of its C-terminal domains. The alpha-helical nature of the
      domain-connecting region is, therefore, critical for the Mip-like proteins.

PMID- 29632828
TI  - Method for estimating protein binding capacity of polymeric systems.
AB  - Composite biomaterials made from synthetic and protein-based polymers are
      extensively researched in tissue engineering. To successfully fabricate a protein
      polymer composite, it is critical to understand how strongly the protein binds to
      the synthetic polymer, which occurs through protein adsorption. Currently, there
      is no cost-effective and simple method for characterizing this interfacial
      binding. To characterize this interfacial binding, we introduce a simple three
      step method that involves: 1) synthetic polymer surface characterisation, 2) a
      quick, inexpensive and robust novel immuno-based assay that uses protein
      extraction compounds to characterize protein binding strength followed by 3) an
      in vitro 2D model of cell culture to confirm the results of the immuno-based
      assay. Fibrinogen, precursor of fibrin, was adsorbed (test protein) on three
      different polymeric surfaces: silicone, poly(acrylic acid)-coated silicone and
      poly(allylamine)-coated silicone. Polystyrene surface was used as a reference.
      Characterisation of the different surfaces revealed different chemistry and
      roughness. The novel immuno-based assay showed significantly stronger binding of
      fibrinogen to both poly(acrylic acid) and poly(allylamine) coated silicone.
      Finally, cell studies showed that the strength of the interaction between the
      protein and the polymer had an effect on cell growth. This novel immuno-based
      assay is a valuable tool in developing composite biomaterials of synthetic and
      protein-based polymers with the potential to be applied in other fields of
      research where protein adsorption onto surfaces plays an important role.

PMID- 29632830
TI  - Editorial.

PMID- 29632829
TI  - Argan oil prevents down-regulation induced by endotoxin on liver fatty acid
      oxidation and gluconeogenesis and on peroxisome proliferator-activated receptor
      gamma coactivator-1alpha, (PGC-1alpha), peroxisome proliferator-activated
      receptor alpha (PPARalpha) and estrogen related receptor alpha (ERRalpha).
AB  - In patients with sepsis, liver metabolism and its capacity to provide other
      organs with energetic substrates are impaired. This and many other
      pathophysiological changes seen in human patients are reproduced in mice injected
      with purified endotoxin (lipopolysaccharide, LPS). In the present study, down
      regulation of genes involved in hepatic fatty acid oxidation (FAOx) and
      gluconeogenesis in mice exposed to LPS was challenged by nutritional intervention
      with Argan oil. Mice given a standard chow supplemented or not with either 6%
      (w/w) Argan oil (AO) or 6% (w/w) olive oil (OO) prior to exposure to LPS were
      explored for liver gene expressions assessed by mRNA transcript levels and/or
      enzyme activities. AO (or OO) food supplementation reveals that, in LPS-treated
      mice, hepatic expression of genes involved in FAOx and gluconeogenesis was
      preserved. This preventive protection might be related to the recovery of the
      gene expressions of nuclear receptors peroxisome proliferator-activated receptor
      alpha (PPARalpha) and estrogen related receptor alpha (ERRalpha) and their
      coactivator peroxisome proliferator-activated receptor gamma coactivator-1alpha,
      (PGC-1alpha). These preventive mechanisms conveyed by AO against LPS-induced
      metabolic dysregulation might add new therapeutic potentialities in the
      management of human sepsis.

PMID- 29632831
TI  - Identification of a nicotinamide/nicotinate mononucleotide adenylyltransferase in
      Giardia lamblia (GlNMNAT).
AB  - Giardia lamblia is an intestinal protozoan parasite that causes giardiasis, a
      disease of high prevalence in Latin America, Asia and Africa. Giardiasis leads to
      poor absorption of nutrients, severe electrolyte loss and growth retardation. In
      addition to its clinical importance, this parasite is of special biological
      interest due to its basal evolutionary position and simplified metabolism, which
      has not been studied thoroughly. One of the most important and conserved
      metabolic pathways is the biosynthesis of nicotinamide adenine dinucleotide
      (NAD). This molecule is widely known as a coenzyme in multiple redox reactions
      and as a substrate in cellular processes such as synthesis of Ca2+ mobilizing
      agents, DNA repair and gene expression regulation. There are two pathways for NAD
      biosynthesis, which converge at the step catalyzed by nicotinamide/nicotinate
      mononucleotide adenylyltransferase (NMNAT, EC 2.7.7.1/18). Using bioinformatics
      tools, we found two NMNAT sequences in Giardia lamblia (glnmnat-a and glnmnat-b).
      We first verified the identity of the sequences in silico. Subsequently, glnmnat
      a was cloned into an expression vector. The recombinant protein (His-GlNMNAT) was
      purified by nickel-affinity binding and was used in direct in vitro enzyme assays
      assessed by C18-HPLC, verifying adenylyltransferase activity with both
      nicotinamide (NMN) and nicotinic acid (NAMN) mononucleotides. Optimal reaction pH
      and temperature were 7.3 and 26  degrees C. Michaelis-Menten kinetics were
      observed for NMN and ATP, but saturation was not accomplished with NAMN, implying
      low affinity yet detectable activity with this substrate. Double-reciprocal plots
      showed no cooperativity for this enzyme. This represents an advance in the study
      of NAD metabolism in Giardia spp.

PMID- 29632832
TI  - Uncovering the role of the flexible C-terminal tail: A model study with Strep
      tagged GFP.
AB  - Recently, it has been recognized that, much like an electric current in an
      electric circuit, dynamic disruptions from flexible, unstructured regions distal
      to the active region are transferred through the contact network to the active
      site and influence protein stability and/or function. As transmembrane proteins
      frequently possess the beta-barrel structure, studies of proteins with this
      topology are required. The unstructured lid segments of the beta-barrel GFP
      protein are conserved and could play a role in the backbone stabilization
      required for chromophore function. A study of the disordered C-terminus and the
      function within the lid is necessary. In this study, we entirely truncated the
      flexible C-terminal tail and investigated the N-terminal Strep-tagged GFP by
      fluorescence spectroscopy, and the temperature- and GdnHCl-induced unfolding by
      circular dichroism. The introduction of the unstructured Strep-tag itself changed
      the unfolding pathway. Truncating the entire flexible tail did not decrease the
      fluorescence intensity to a large extent; however, the protein stability changed
      dramatically. The temperature for half-denaturation T1/2 changed significantly
      from 79  degrees C for the wild-type to 72.8  degrees C for the mutant. Unfolding
      kinetics at different temperatures have been induced by 4 M GdnHCl, and the
      apparent Arrhenius activation energy decreased by 40% as compared to the wild
      type.

PMID- 29632833
TI  - The peptidyl-prolyl cis-trans isomerase activity of the wheat cyclophilin, TaCypA
      1, is essential for inducing thermotolerance in Escherichia coli.
AB  - Growth at high temperatures is one of the desired features for industrial
      applications of microbes, as it results in decrease in contamination and enhanced
      solubility of certain substrates. In this study, it is demonstrated that
      heterologous expression of a wheat cyclophilin, TaCypA-1, confers thermotolerance
      to Escherichia coli. The TaCypA-1 possesses peptidyl-prolyl cis-trans isomerase
      (PPIase) activity that catalyses cis to trans isomerization of the peptidyl
      prolyl bonds, a rate limiting step in protein folding. Expression of deleted
      mutants of TaCypA-1, that lacked PPIase activity, resulted in abrogation of
      thermotolerance, providing the first evidence that this activity plays a key role
      in stress tolerance of cells and can be exploited for industrial applications.
      Further, we also demonstrate that TaCypA-1 interacts with calmodulin (CaM), and
      the CaM-binding domain is localized to amino acid residues 51-71 in the N
      terminus region.

PMID- 29632834
TI  - Assessing Na+/H+ exchange and cell effector functionality in metastatic breast
      cancer.
AB  - Metastasis is the leading cause of mortality in patients with breast cancer. In
      triple-negative breast cancer, high recurrence rates, increased invasive capacity
      of cells, and their aggressive ability to metastasize at secondary sites dictate
      patient survival. The Na+/H+ exchanger isoform 1 (NHE1) plays a critical role in
      controlling the metastatic potential of these cells. Its activity results in an
      elevation of intracellular pH and in extracellular acidification, a key step in
      the establishment of the tumor microenvironment. Here, we describe assays for
      characterization of Na+/H+ exchanger activity and its related downstream
      physiological effects on triple-negative breast cancer cells. Na+/H+ exchanger
      activity can be routinely and rapidly measured in live cells with a fluorometric
      assay that assesses changes in intracellular pH. Characterization of downstream
      cell effector function as a result of Na+/H+ exchanger activation can be
      evaluated by measuring directed cell migration and invasion. Cell migration is
      assessed with wound-healing assays, where a gap is introduced in a confluent
      monolayer of cells and the rate of gap closure is measured over time. Cell
      invasion is assessed in the short-term by transwell invasion assays that track
      cell movement through an extracellular matrix. Long-term invasiveness, growth and
      proliferation can be assessed with 3-D invasion assays using transwell inserts
      fitted with specialized scaffolds optimized for 3-D cell culture. Taken together
      these assays provide powerful tools for testing the effects of altering Na+/H+
      exchanger activity with chemical inhibition on the metastatic capacity of breast
      cancer cells.

PMID- 29632835
TI  - A spinach O-acetylserine(thiol)lyase homologue, SoCSaseLP, suppresses cysteine
      biosynthesis catalysed by other enzyme isoforms.
AB  - An enzyme, O-acetylserine(thiol)lyase (OASTL), also known as O-acetylserine
      sulfhydrylase or cysteine synthase (CSase), catalyses the incorporation of
      sulfide into O-acetylserine and produces cysteine. We previously identified a
      cDNA encoding an OASTL-like protein from Spinacia oleracea, (SoCSaseLP), but a
      recombinant SoCSaseLP produced in Escherichia coli did not show OASTL activity.
      The exon-intron structure of the SoCSaseLP gene shared conserved structures with
      other spinach OASTL genes. The SoCSaseLP and a Beta vulgaris homologue protein,
      KMT13462, comprise a unique clade in the phylogenetic tree of the OASTL family.
      Interestingly, when the SoCSaseLP gene was expressed in tobacco plants, total
      OASTL activity in tobacco leaves was reduced. This reduction in total OASTL
      activity was most likely caused by interference by SoCSaseLP with cytosolic
      OASTL. To investigate the possible interaction of SoCSaseLP with a spinach
      cytosolic OASTL isoform SoCSaseA, a pull-down assay was carried out. The
      recombinant glutathione S-transferase (GST)-SoCSaseLP fusion protein was
      expressed in E. coli together with the histidine-tagged SoCSaseA protein, and the
      protein extract was subjected to glutathione affinity chromatography. The
      histidine-tagged SoCSaseA was co-purified with the GST-SoCSaseLP fusion protein,
      indicating the binding of SoCSaseLP to SoCSaseA. Consistent with this
      interaction, the OASTL activity of the co-purified SoCSaseA was reduced compared
      with the activity of SoCSaseA that was purified on its own. These results
      strongly suggest that SoCSaseLP negatively regulates the activity of other
      cytosolic OASTL family members by direct interaction.

PMID- 29632836
TI  - Screening of endophytic sources of exopolysaccharides: Preliminary
      characterization of crude exopolysaccharide produced by submerged culture of
      Diaporthe sp. JF766998 under different cultivation time.
AB  - Endophytic fungi have been described as producers of important bioactive
      compounds; however, they remain under-exploited as exopolysaccharides (EPS)
      sources. Therefore, this work reports on EPS production by submerged cultures of
      eight endophytes isolated from Piper hispidum Sw., belonging to genera Diaporthe,
      Marasmius, Phlebia, Phoma, Phyllosticta and Schizophyllum. After fermentation for
      96 h, four endophytes secreted EPS: Diaporthe sp. JF767000, Diaporthe sp.
      JF766998, Diaporthe sp. JF767007 and Phoma herbarumJF766995. The EPS from
      Diaporthe sp. JF766998 differed statistically from the others, with a higher
      percentage of carbohydrate (91%) and lower amount of protein (8%). Subsequently,
      this fungus was grown under submerged culture for 72, 96 and 168 h (these EPS
      were designated EPSD1-72, EPSD1-96 and EPSD1-168) and the differences in
      production, monosaccharide composition and apparent molecular were compared. The
      EPS yields in mg/100 mL of culture medium were: 3.0 +/- 0.4 (EPSD1-72), 15.4 +/-
      2.2 (EPSD1-96) and 14.8 +/- 1.8 (EPSD1-168). The EPSD1-72 had high protein
      content (28.5%) and only 71% of carbohydrate; while EPSD1-96 and EPSD1-168 were
      composed mainly of carbohydrate (~95 and 100%, respectively), with low protein
      content (~5%) detected at 96 h. Galactose was the main monosaccharide component
      (30%) of EPSD1-168. Differently, EPSD1-96 was rich in glucose (51%), with
      molecular weight of 46.6 kDa. It is an important feature for future
      investigations, because glucan-rich EPS are reported as effective antitumor
      agents.

PMID- 29632837
TI  - Nitric oxide overcomes Cd and Cu toxicity in in vitro-grown tobacco plants
      through increasing contents and activities of rubisco and rubisco activase.
AB  - Toxic heavy metals such as cadmium (Cd) and copper (Cu) are global problems that
      are a growing threat to the environment. Despite some heavy metals are required
      for plant growth and development, others are considered toxic elements and do not
      play any known physiological role in plant cells. Elevated doses of Cd or Cu
      cause toxicity in plants and generate damages due to the stress condition and
      eventually cause a significant reduction in quantity and quality of crop plants.
      The nitric oxide (NO) donor sodium nitroprusside (SNP) is reported to alleviate
      the toxicity of some heavy metals like Cd and Cu. In the current study, the role
      of NO in alleviating stresses of Cd and Cu was investigated in in vitro-grown
      tobacco (Nicotiana tabacum) Based on plant growth, total chlorophyll contents,
      contents and activities of rubisco and rubisco activase. According to the results
      of this study, the growth and total chlorophyll contents of Cd/Cu stressed plants
      were hugely decreased in the absence of SNP, while the supplementation of SNP
      resulted in a significant increase of both fresh weight and total chlorophyll
      contents. Remarkable reductions of Rubisco and rubisco activase contents and
      activities were observed in Cd and Cu-induced plants. SNP supplementation showed
      the highest contents and activities of rubisco and rubisco activase compared to
      the control and Cu/Cd-stressed plants. Taken together, our findings suggest that
      SNP could play a protective role in regulation of plant responses to abiotic
      stresses such as Cd and Cu by enhancing Rubisco and Rubisco activase.

PMID- 29632838
TI  - Association of human mitochondrial lysyl-tRNA synthetase with HIV-1 GagPol does
      not require other viral proteins.
AB  - In human, the cytoplasmic (cLysRS) and mitochondrial (mLysRS) species of lysyl
      tRNA synthetase are encoded by a single gene. Following HIV-1 infection, mLysRS
      is selectively taken up into viral particles along with the three tRNALys
      isoacceptors. The GagPol polyprotein precursor is involved in this process. With
      the aim to reconstitute in vitro the HIV-1 tRNA3Lys packaging complex, we first
      searched for the putative involvement of another viral protein in the selective
      viral hijacking of mLysRS only. After screening all the viral proteins, we
      observed that Vpr and Rev have the potential to interact with mLysRS, but that
      this association does not take place at the level of the assembly of mLysRS into
      the packaging complex. We also show that tRNA3Lys can form a ternary complex with
      the two purified proteins mLysRS and the Pol domain of GagPol, which mimicks its
      packaging complex.

PMID- 29632839
TI  - Anti-inflammatory and antinociceptive activities of Bauhinia monandra leaf
      lectin.
AB  - A galactose-specific lectin from Bauhinia monandra leaves (BmoLL) has been
      purified through ammonium sulfate fractionation followed by guar gel affinity
      chromatography column. This study aimed to evaluate the potential anti
      inflammatory and antinociceptive activity of pure BmoLL in mice. Anti
      inflammatory activity was evaluated by 1% carrageenan-induced inflammation in
      mice treated with BmoLL. Acetic acid-induced abdominal writhing and hot plate
      methods evaluated antinociceptive activity. BmoLL significantly inhibited the
      carrageenan-induced paw edema by 47% (30 mg/kg) and 60.5% (60 mg/kg);
      acetylsalicylic acid (ASA, 100 mg/kg) showed inhibition of 70.5%, in comparison
      to controls. Leukocyte migration, an immune response to the inflammation process,
      was significantly reduced in presence of BmoLL; in mice treated with ASA the
      decrease in leukocyte migration was similar to 15 mg/kg of the lectin. BmoLL at
      doses of 15, 30 and 60 mg/kg significantly reduced the number of animal
      contortions by 43.1, 50.1 and 71.3%, respectively. BmoLL leukocyte migration was
      significantly reduced; in mice treated with ASA the decrease in leukocyte
      migration was similar to 15 mg/kg of the lectin. BmoLL at doses of 15, 30 and 60
      mg/kg significantly reduced the number of animal contortions by 43.1, 50.1 and
      71.3%, respectively. The lectin (30 and 60 mg/kg) showed a significant effect in
      the hot plate assay. BmoLL anti-inflammatory and antinociceptive effects were
      dose-dependent. The search for new and natural compounds, with minimal side
      effects, to control pain and inflammation, is constantly increasing. BmoLL has
      great potential as a natural anti-inflammatory product that can be explored for
      pharmacological purposes.

PMID- 29632840
TI  - The proto-oncogenic protein TAL1 controls TGF-beta1 signaling through interaction
      with SMAD3.
AB  - TGF-beta1 is involved in many aspects of tissue development and homeostasis
      including hematopoiesis. The TAL1 transcription factor is also an important
      player of this latter process and is expressed very early in the myeloid and
      erythroid lineages. We previously established a link between TGF-beta1 signaling
      and TAL1 by showing that the cytokine was able to induce its proteolytic
      degradation by the ubiquitin proteasome pathway. In this manuscript we show that
      TAL1 interacts with SMAD3 that acts in the pathway downstream of TGF-beta1
      association with its receptor. TAL1 expression strengthens the positive or
      negative effect of SMAD3 on various genes. Both transcription factors activate
      the inhibitory SMAD7 factor through the E box motif present in its
      transcriptional promoter. DNA precipitation assays showed that TAL1 present in
      Jurkat or K562 cells binds to this SMAD binding element in a SMAD3 dependent
      manner. SMAD3 and TAL1 also inhibit several genes including ID1, hTERT and TGF
      beta1 itself. In this latter case TAL1 and SMAD3 can impair the positive effect
      exerted by E47. Our results indicate that TAL1 expression can modulate TGF-beta1
      signaling by interacting with SMAD3 and by increasing its transcriptional
      properties. They also suggest the existence of a negative feedback loop between
      TAL1 expression and TGF-beta1 signaling.

PMID- 29632841
TI  - The effectiveness and safety of Iranian herbal medicines for treatment of
      premenstrual syndrome: A systematic review.
AB  - Objective: Premenstrual syndrome (PMS) is one of the most common problems among
      women of reproductive age. The popularity of complementary/alternative therapies
      has grown in recent years, and these treatments have been more commonly used by
      women (48.9%) than men (37.8%). The aim of this systematic review was to assess
      effectiveness and safety of Iranian herbal medicines for treatment of
      premenstrual syndrome. Methods: PubMed, Scopus, Cochrane, and Google Scholar were
      searched along with SID, Magiran and Irandoc up to Dec 2017.Inclusion criteria
      consist of Iranian, published, randomized controlled trials (RCTs) using Iranian
      herbal medicine for treatment of reproductive age women with PMS. Eventually
      Eighteen RCTs met the inclusion criteria. Results: Overall, studies have shown
      that Vitex agnuscastus, Hypericum perforatum,Matricaria chamomilla, saffron,
      Curcumin, Melissa officinalis, Zataria multiflora,Wheat Germ Extract, Echinophora
      platyloba, Foeniculum vulgare, Valerian root extract,Citrus sinensis, Zingiber
      officinale and Flax seed might alleviate symptoms of PMS. Conclusion: This
      research demonstrated efficacy and safety of Iranian herbal medicines in
      alleviating PMS. Therefore, herbal medicine can be regarded as an alternative
      treatment for women suffering from PMS.

PMID- 29632842
TI  - The field efficacy of Nigella sativa and Berberis vulgaris methanolic extracts
      against Haemoproteus columbae.
AB  - Objective: The methanolic extracts of Nigella sativaL. seeds (MENS) and Berberis
      vulgaris L.(MEBV) were investigated for treatment of Haemoproteus columbae
      infected pigeons (Columba livia domestica). Materials and Methods: One hundred
      twenty naturally-infected pigeons were randomly divided into four groups of
      thirty each. Two groups were treated separately with the extracts, while the
      positive and negative control groups were given buparvaquone (Butalex(r)) and
      distilled water, respectively. The parasitaemia rate was calculated in all groups
      before and after the experiment at four-day intervals for16 days. Results: The
      results showed a high therapeutic effect for MENS with a progressive decrease in
      average parasitaemia rate from 18.17% before treatment to 0.73% at the end of
      treatment (p<0.05), while Butalex(r) was able to suppress the parasitemia rate
      from 18.90% before treatment to 0.23% at the end of experiment (p<0.05). However,
      no significant changes in parasitemia rate were evident in groups treated with
      MEBV (p>0.05). Conclusion: Methanolic extracts of N. sativa showed therapeutic
      effects against H. columbae and may be regarded as a suitable choice for further
      studies to develop new drugs against blood parasites, in both animals and human
      beings.

PMID- 29632843
TI  - Evaluation of cytotoxic effects and acute and chronic toxicity of aqueous extract
      of the seeds of Calycotome villosa (Poiret) Link (subsp. intermedia) in rodents.
AB  - Objective: The present investigation was carried out to evaluate the safety of an
      aqueous extract of the seeds of Calycotome villosa (Poiret) Link (subsp.
      intermedia) by determining its cytotoxicity and potential toxicity after acute
      and sub-chronic administration in rodents. Materials and Methods: Cytotoxic
      activity was tested in cancer and non-cancer cell lines HeLa, Mel-5, HL-60 and
      3T3. Acute toxicity tests were carried out in mice by a single oral
      administration of Calycotome seed-extract (0 - 12 g/kg) as well as
      intraperitoneal doses of 0 - 5 g/kg. Sub-chronic studies were conducted in Wistar
      rats by administration of oral daily doses for up to 90 days. Changes in body and
      vital organ weights, mortality, haematology, clinical biochemistry and histologic
      morphology were evaluated. Results: The lyophilized aqueous extract of C. villosa
      exhibited a low cytotoxicity in all cell lines tested with an IC50 > 100 ug/ml.
      In the acute study in mice, intra-peritoneal administration caused dose-dependent
      adverse effects and mortality with an LD50 of 4.06 +/- 0.01 g/kg. In the chronic
      tests, neither mortality nor visible signs of lethality was seen in rats. Even
      AST and ALT were not affected while a significant decrease in serum glucose
      levels, at 300 and 600 mg/kg was detected. Histopathological examination of the
      kidney and liver did not show any alteration or inflammation at the end of
      treatment. Conclusion: In conclusion, the aqueous extract of C. villosa seed
      appeared to be non-toxic and did not produce mortality or clinically significant
      changes in the haematological and biochemical parameters in rats.

PMID- 29632844
TI  - In vitro and in vivo evaluations of Pelargonium roseum essential oil activity
      against Trichomonas gallinae.
AB  - Objective: Pelargonium roseum Willd. (Geraniaceae) is widely grown as an
      ornamental plant due to its strong pleasant rose-like odor. The present study
      evaluates the antitrichomonal effect of P. roseum essential oil (EO) against
      Trichomonas gallinae both in vitro and in vivo and compares it to that of
      metronidazole (MTZ) as a standard antitrichomonal drug. Materials and Methods: In
      vitro assays were accomplished in multi-well plates containing MTZ and EO at
      final concentrations of 2.5, 5, 10, 20, 50, and 100 MUg/mL. In vivo assay was
      carried out on 40 experimentally infected pigeons receiving MTZ and EO at doses
      of 25 and 50 mg/kg. Results: The 24-hr MIC of MTZ was 10 ug/mL, while for EO it
      was 20 ug/mL. Treatment with MTZ 50 mg/kg after 4 days led to full recovery of
      infected pigeons however EO 50 mg/kg resulted in the same outcome after 5 days.
      No mortality or clinical side effects were seen in treated birds. Conclusion: The
      present study introduced P. roseum EO as a potent natural antitrichomonal agent
      effective against T. gallinae. Bioactive components of P. roseum can be used as
      potential therapeutic compounds in development of novel antitrichomonal drugs.

PMID- 29632845
TI  - Protective effects of long-term administration of Ziziphus jujuba fruit extract
      on cardiovascular responses in L-NAME hypertensive rats.
AB  - Objective: Ziziphus jujuba stimulates the release of nitric oxide (NO). Because
      NO is involved in cardiovascular regulations, in this study the effects of
      hydroalcoholic extract of Z. jujuba on cardiovascular responses in acute NG-nitro
      L-arginine methyl ester (L-NAME) hypertensive rats were evaluated. Materials and
      Methods: Rats were divided into 6 group (n=6): 1) saline, 2) L-NAME received
      (10mg/kg) intravenously, 3) sodium nitroprusside (SNP) (50ug/kg)+L-NAME group
      received SNP before L-NAME and 4-6) three groups of Z. jujuba (100, 200 and
      400mg/kg) that treated for four weeks and on the 28th day, L-NAME was injected.
      Femoral artery and vein were cannulated for recording cardiovascular responses
      and drug injection, respectively. Systolic blood pressure (SBP), Mean arterial
      pressure (MAP) and heart rate (HR) were recorded continuously. Maximal changes
      (?) of SBP, MAP and HR were calculated and compared to control and L-NAME groups.
      Results: In L-NAME group, maximal DeltaSBP (L-NAME: 44.15+/-4.0 mmHg vs control:
      0.71+/-2.1 mmHg) and DeltaMAP (L-NAME: 40.8+/-4.0 mmHg vs control: 0.57+/-1.6
      mmHg) significantly increased (p<0.001 in both) but ?HR was not significant as
      compared to control (p>0.05). All doses of Z. jujuba attenuated maximal ?SBP and
      ?MAP induced by L-NAME but only the lowest dose (100 mg/kg) had significant
      effects (DeltaSBP: 20.36+/-5.6 mmHg vs L-NAME: 44.1+/-4.0 mmHg and DeltaMAP:
      20.8+/-4.5 mmHg vs L-NAME: 40.8+/-3.8 mmHg (p<0.05 to p<0.01)). The ?HR at three
      doses was not significantly different from that of L-NAME group (p>0.05).
      Conclusion: Because long-term consumption of Z. jujuba extract, especially its
      lowest dose, attenuated cardiovascular responses induced by L-NAME, we suggest
      that Z. jujuba has potential beneficial effects in prevention of hypertension
      induced by NO deficiency.

PMID- 29632846
TI  - Effects of IMODTM on angiogenesis, miR-503 and CDC25 expression levels in heart
      tissue of diabetic male rats.
AB  - Objective: Diabetes is associated with vascular complications and impaired
      angiogenesis. Since angiogenesis plays a crucial role in vascular homeostasis in
      ischemic heart diseases, in this study, the effect of IMODTM on miR-503 and CDC25
      expression level which are altered in impaired angiogenesis were investigated in
      heart tissue of diabetic rats. Materials and Methods: Forty male Wistar rats (200
      250 g) were randomly classified into 4 groups: control (C), IMODTM (I), diabetes
      (D), and diabetes+IMODTM (D+I). For induction of experimental diabetes in
      animals, a single dose of streptozotocin (STZ; 60mg/kg) was injected
      intraperitoneally. After 8 weeks of treatment with IMODTM (20 mg/kg/day), heart
      tissue samples were removed and used for measurement of miR-503 and CDC25
      expression level as well as histological studies. Results: Results of this study
      showed that diabetes decreased heart tissue angiogenesis which was associated
      with increased miR-503 and reduced CDC25 expression levels (p<0.05) and IMODTM
      could reduce the expression of miR-503 and increase the expression of CDC25
      (p<0.05). Moreover, IMODTM extensively induced angiogenesis in the heart tissue
      of diabetic group. However, IMODTM had no significant effect on expressions of
      miR-503 and CDC25, or angiogenesis in healthy rats. Conclusion: This study showed
      that IMODTM is able to increase angiogenesis in the heart tissue of diabetic
      rats. The angiogenic effect of IMODTM is associated with reduction of miR-503
      expression and increased expression of CDC25.

PMID- 29632847
TI  - A comparison of the effects of Portulaca oleracea seeds hydro-alcoholic extract
      and Vitamin C on biochemical, hemodynamic and functional parameters in cardiac
      tissue of rats with subclinical hyperthyroidism.
AB  - Objective: The present study was performed to evaluate the effects of hydro
      alcoholic extract of Portulaca oleracea (P. oleracea) seeds and Vitamin C on
      biochemical and hemodynamic parameters in cardiac tissue of rats with subclinical
      hyperthyroidism. Materials and Methods: Forty eight male rats were divided into
      six groups of 8 and treated for 4 weeks. T4 group received daily injection of
      levothyroxine sodium (20 MUg/kg) and control group was given daily injection of
      saline. T4-Po groups were given T4 plus 100, 200, and 400 mg/kg of P. oleracea
      seeds extract in drinking water daily. T4-Vit C group received T4 plus daily
      injection of Vitamin C (100 mg/kg). At the end of the experiment, body weight,
      serum free T4 level, left ventricular developed pressure (LVDP), malondialdehyde
      (MDA) and total thiol levels were measured. Results: Free T4 levels were
      increased in all groups that were treated with T4. Weight gain was decreased in
      T4 and T4-Po100 groups compared to control group (p<0.001 and p<0.05). However,
      body weight was increased in T4-Po (200 and 400) and T4-Vit C groups compared to
      T4 group. LVDP was increased in T4 group compared to control group but, LVDP was
      decreased in T4-Po and T4-Vit C groups. Malondialdehyde was decreased in T4-Po
      groups and T4-Vit C group compared to T4 group. Total thiol groups were increased
      in T4-Po (200 and 400) and T4-Vit C groups compared to T4 group. Conclusion: The
      results showed that P. oleracea extract has a protective effect on cardiac
      dysfunction due to subclinical hyperthyroidism induced by levothyroxine sodium in
      rats.

PMID- 29632848
TI  - Preventive effects of the aqueous extract of Cichorium intybus L. flower on
      ethylene glycol-induced renal calculi in rats.
AB  - Objective: Urolithiasis remains a global problem. Despite the availability of
      numerous methods, no definite therapeutic agent has been yet introduced for the
      prevention or treatment of kidney stones. In this study, we evaluated the
      possible preventive effects of aqueous extract of Cichorium intybus L. (chicory)
      flowers on ethylene glycol-induced renal calculi in rats. Materials and Methods:
      A total of 24 Wistar rats were randomly divided into four groups and were treated
      for 30 days. Group A received drinking tap water, while groups B, C, and D were
      administered with 1% ethylene glycol for induction of calcium oxalate stone
      formation. Rats in groups C and D received intraperitoneal injections of the
      aqueous extract of chicory flowers (50 and 200 mg/kg, respectively) since the
      first day of the experiment. The urine volume, urine pH, and urinary levels of
      oxalate, citrate, calcium, uric acid, and creatinine as well as serum levels of
      calcium, uric acid, and creatinine were measured. After 30 days, the rats'
      kidneys were removed and prepared for histological evaluation of calcium oxalate
      deposits. One-way analysis of variance (ANOVA), followed by Tukey's test, was
      performed, using SPSS version 20. Results: The number of calcium oxalate crystals
      was significantly higher in group B (ethylene glycol-only treated animals),
      compared to group A (control), group C (50 mg/kg of aqueous extract), and group D
      (200 mg/kg of aqueous extract) (p<0.05). On day 30, the urine level of citrate,
      oxalate (p>0.05), and creatinine (p<0.05), as well as urine pH (p<0.05) decreased
      in groups C and D, compared to group B. Also, urine calcium level, urine uric
      acid (p>0.05), and urine volume (p<0.05) were higher in group D, compared to
      group B. In addition, the serum level of calcium, creatinine (p<0.05), and uric
      acid (p<0.001) decreased in groups C and D. Conclusion: The aqueous extract of
      chicory flower (50 mg/kg) could reduce the number of calcium oxalate deposits in
      the urine and reduce the level of serum parameters.

PMID- 29632849
TI  - Doxorubicin-induced renal inflammation in rats: Protective role of Plantago
      major.
AB  - Objective: The aim of the present study was to evaluate the possible protective
      effect of Plantago major (P. major) extract against doxorubicin (DXR)-induced
      renal inflammation in rats. Materials and Methods: 80 male albino rats were
      randomly divided into 8 groups as follows: control, DXR, Ext (extract) 600,
      Ext1200, dexamethasone+DXR, vitamin E+DXR, Ext600+DXR, and Ext1200+DXR. Duration
      of the study was 35 days and DXR was intravenously injected on the 7th day of the
      experiment. Tumor necrosis factor-alpha (TNF-alpha) production and monocyte
      chemoattractant protein-1 (MCP-1) expression levels were assessed in the left
      kidney. Serum creatinine concentration and osmolarity were determined on the 1st,
      14th, 21st, 28th and 35th days of the experiment. Results: DXR caused a
      significant increase in renal expression of MCP-1 and TNF-alpha production
      compared to control animals. Administration of dexamethasone, vitamin E and P.
      major extract significantly improved the expression of these inflammatory
      mediators compared to DXR group. Compared to day 1 in DXR group, serum osmolarity
      showed a significant increase on days 21, 28 and 35. Also, on these days, serum
      osmolarity in DXR group was significantly higher than that on the same days in
      control group. In Vit E+DXR and Ext 1200+DXR groups, there was no significant
      changes in serum osmolarity among different days of the study. However, in these
      groups, serum osmolarity on days 21, 28 and 35 showed a significant decrease
      compared to the same days in DXR group. Conclusion: Present results suggest that
      hydroethanolic extract of P. major protected renal tissue against DXR-induced
      renal inflammation.

PMID- 29632850
TI  - Intraoperative Radiotherapy With INTRABEAM: Technical and Dosimetric
      Considerations.
AB  - Purpose: We evaluate dose characteristics and clinical applications of treatment
      accessories used in intraoperative radiotherapy (IORT) and make site-specific
      recommendations for their optimal use. Methods and materials: Dose measurements
      were performed for a low energy (50 kV) X-ray INTRABEAM source. For spherical,
      flat, surface, and needle applicators, the following dosimetric parameters were
      measured: depth-dose (DD) profiles, surface dose (Ds), output factors (OF), and
      target dose homogeneity (DH). Optical density versus exposure calibration films
      were employed to obtain 2-dimensional dose distributions in planes parallel and
      perpendicular to beam direction. Film results were verified via repeat dose
      measurements with a parallel-plate ionization chamber in a custom water tank. The
      impact of applicator design on dose distributions was evaluated. Results:
      Spherical applicators are commonly used for treating the inner-surface of breast
      lumpectomy cavity. Flat and surface applicators provide uniform planar dose for
      head and neck, abdomen, and pelvis targets. Needle applicators are designed for
      kypho-IORT of spinal metastasis. Typically, larger applicators produce a more
      homogeneous target dose region with lower surface dose, but require longer
      treatment times. For 4-cm diameter spherical, flat, and surface applicators, dose
      rates (DR) at their respective prescription points were found to be: 0.8, 0.3,
      and 2.2 Gy/min, respectively. The DR for a needle applicator was 7.04 Gy/min at 5
      mm distance from the applicator surface. Overall, film results were in excellent
      agreement with ion-chamber data. Conclusion: IORT may be delivered with a variety
      of site-specific applicators. Appropriate applicator use is paramount for safe,
      effective, and efficient IORT delivery. Results of this study should help
      clinicians assure optimized target dose coverage and reduced normal tissue
      exposure.

PMID- 29632851
TI  - Treatment of Genetic Forms of Nephrotic Syndrome.
AB  - Idiopathic steroid-resistant nephrotic syndrome (SRNS) is most frequently
      characterized by focal segmental glomerulosclerosis (FSGS) but also other
      histological lesions, such as diffuse mesangial sclerosis. In the past two
      decades, a multitude of genetic causes of SRNS have been discovered raising the
      question of effective treatment in this cohort. Although no controlled studies
      are available, this review will discuss treatment options including pharmacologic
      interventions aiming at the attenuation of proteinuria in genetic causes of SRNS,
      such as inhibitors of the renin-angiotensin-aldosterone system and indomethacin.
      Also, the potential impact of other interventions to improve podocyte stability
      will be addressed. In this respect, the treatment with cyclosporine A (CsA) is of
      interest, since a podocyte stabilizing effect has been demonstrated in various
      experimental models. Although clinical response to CsA in children with genetic
      forms of SRNS is inferior to sporadic SRNS, some recent studies show that partial
      and even complete response can be achieved even in individual patients inherited
      forms of nephrotic syndrome. Ideally, improved pharmacologic and molecular
      approaches to induce partial or even complete remission will be available in the
      future, thus slowing or even preventing the progression toward end-stage renal
      disease.

PMID- 29632852
TI  - Monitoring Circulation During Transition in Extreme Low Gestational Age Newborns:
      What's on the Horizon?
AB  - Echocardiography and near-infrared spectroscopy have significantly changed our
      view on hemodynamic transition of the extreme preterm infant. Instead of focusing
      on maintaining an arbitrary target value of blood pressure, we aim for
      circulatory well-being by a comprehensive holistic assessment of markers of
      cardiovascular instability. Most of these clinical and biochemical indices are
      influenced by transition itself and remain poor discriminators to identify
      patients with a potential need for therapeutic intervention. At the same time,
      the evolution in data capturing and storage has led to a change in our approach
      to monitor vital parameters. Continuous trend monitoring has become more and more
      relevant. By using signal extraction methods, changes in trends over time can be
      quantified. In this review, we will discuss the impact of these innovations on
      the current monitoring practices and explore some of the potential benefits these
      techniques may have in improving real-time detection of extreme low birth weight
      infants at risk for morbidity related to impaired hemodynamic transition.

PMID- 29632853
TI  - Effects of a School-Based Sports Program on Physical Fitness, Physical Activity,
      and Cardiometabolic Health in Youth With Physical Disabilities: Data From the
      Sport-2-Stay-Fit Study.
AB  - Objective: To investigate the effects of a school-based once-a-week sports
      program on physical fitness, physical activity, and cardiometabolic health in
      children and adolescents with a physical disability. Methods: This controlled
      clinical trial included 71 children and adolescents from four schools for special
      education [mean age 13.7 (2.9) years, range 8-19, 55% boys]. Participants had
      various chronic health conditions including cerebral palsy (37%), other
      neuromuscular (44%), metabolic (8%), musculoskeletal (7%), and cardiovascular
      (4%) disorders. Before recruitment and based on the presence of school-based
      sports, schools were assigned as sport or control group. School-based sports were
      initiated and provided by motivated experienced physical educators. The sport
      group (n = 31) participated in a once-a-week school-based sports program for 6
      months, which included team sports. The control group (n = 40) followed the
      regular curriculum. Anaerobic performance was assessed by the Muscle Power Sprint
      Test. Secondary outcome measures included aerobic performance, VO2 peak,
      strength, physical activity, blood pressure, arterial stiffness, body
      composition, and the metabolic profile. Results: A significant improvement of 16%
      in favor of the sport group was found for anaerobic performance (p = 0.003). In
      addition, the sport group lost 2.8% more fat mass compared to the control group
      (p = 0.007). No changes were found for aerobic performance, VO2 peak, physical
      activity, blood pressure, arterial stiffness, and the metabolic profile.
      Conclusion: Anaerobic performance and fat mass improved following a school-based
      sports program. These effects are promising for long-term fitness and health
      promotion, because sports sessions at school eliminate certain barriers for
      sports participation and adding a once-a-week sports session showed already
      positive effects for 6 months. Clinical Trial Registration: This trial was
      registered with the Dutch Trial Registry (NTR4698).

PMID- 29632854
TI  - Vaginal Microbiomes Associated With Aerobic Vaginitis and Bacterial Vaginosis.
AB  - A healthy vaginal microbiota is considered to be significant for maintaining
      vaginal health and preventing infections. However, certain vaginal bacterial
      commensal species serve an important first line of defense of the body. Any
      disruption of this microbial barrier might result in a number of urogenital
      conditions including aerobic vaginitis (AV) and bacterial vaginosis (BV). The
      health of the vagina is closely associated with inhabitant microbiota.
      Furthermore, these microbes maintain a low vaginal pH, prevent the acquisition of
      pathogens, stimulate or moderate the local innate immune system, and further
      protect against complications during pregnancies. Therefore, this review will
      focus on vaginal microbial "health" in the lower reproductive tract of women and
      on the physiological characteristics that determine the well-being of
      reproductive health. In addition, we explore the distinct versus shared
      characteristics of BV and AV, which are commonly associated with increased risk
      for preterm delivery.

PMID- 29632856
TI  - E-Cigarette Use Among Adolescents: An Overview of the Literature and Future
      Perspectives.
AB  - Background: Electronic cigarettes (e-cigarettes) are rapidly emerging into a new
      trend among adolescents, signaling a new epoque, that of vapers. E-cigarettes are
      battery-powered nicotine delivery devices that heat a typically flavoring liquid
      solution into an aerosol mist that users inhale, allowing them to imitate the act
      of conventional smoking. There are concerns about the impact of e-cigarettes at
      both individual and public health level. Aim: To discuss the characteristics of
      the most vulnerable, to become e-cigarette users, group of adolescents and to
      further highlight their behaviors and characteristics. Methods: An electronic
      search in PubMed, EMBASE, and Google Scholar databases was conducted, using
      combinations of the following keywords: adolescents, teenagers, e-cigarettes,
      vaping. The search included all types of articles written in English until August
      2017. A total of 100 articles were found, and 25 were finally included in the
      present review. Results: Older age, male gender, conventional smokers, peer
      influence, daily smoking, and heavier smoking are the most common characteristics
      of adolescent e-cigarette users. Conclusion: E-cigarette use is common,
      especially between certain subgroups in the adolescent population. Since e
      cigarette use is increasing and considering that the long term health effects are
      still under investigation, targeted interventions towards more susceptible
      individuals may be an effective prevention strategy.

PMID- 29632855
TI  - Immune-Modulating Perspectives for Low Frequency Electromagnetic Fields in Innate
      Immunity.
AB  - In recent years, the effects of electromagnetic fields (EMFs) on the immune
      system have received a considerable interest, not only to investigate possible
      negative health impact but also to explore the possibility to favorably modulate
      immune responses. To generate beneficial responses, the immune system should
      eradicate pathogens while "respecting" the organism and tolerating irrelevant
      antigens. According to the current view, damage-associated molecules released by
      infected or injured cells, or secreted by innate immune cells generate danger
      signals activating an immune response. These signals are also relevant to the
      subsequent activation of homeostatic mechanisms that control the immune response
      in pro- or anti-inflammatory reactions, a feature that allows modulation by
      therapeutic treatments. In the present review, we describe and discuss the
      effects of extremely low frequency (ELF)-EMF and pulsed EMF on cell signals and
      factors relevant to the activation of danger signals and innate immunity cells.
      By discussing the EMF modulating effects on cell functions, we envisage the use
      of EMF as a therapeutic agent to regulate immune responses associated with wound
      healing.

PMID- 29632857
TI  - Leveraging Citizen Science for Healthier Food Environments: A Pilot Study to
      Evaluate Corner Stores in Camden, New Jersey.
AB  - Over the last 6 years, a coordinated "healthy corner store" network has helped an
      increasing number of local storeowners stock healthy, affordable foods in Camden,
      New Jersey, a city with high rates of poverty and unemployment, and where most
      residents have little or no access to large food retailers. The initiative's
      funders and stakeholders wanted to directly engage Camden residents in evaluating
      this effort to increase healthy food access. In a departure from traditional
      survey- or focus group-based evaluations, we used an evidence-based community
      engaged citizen science research model (called Our Voice) that has been deployed
      in a variety of neighborhood settings to assess how different features of the
      built environment both affect community health and wellbeing, and empower
      participants to create change. Employing the Our Voice model, participants
      documented neighborhood features in and around Camden corner stores through geo
      located photos and audio narratives. Eight adult participants who lived and/or
      worked in a predefined neighborhood of Camden were recruited by convenience
      sample and visited two corner stores participating in the healthy corner store
      initiative (one highly-engaged in the initiative and the other less-engaged), as
      well as an optional third corner store of their choosing. Facilitators then
      helped participants use their collected data (in total, 134 images and 96 audio
      recordings) to identify and prioritize issues as a group, and brainstorm and
      advocate for potential solutions. Three priority themes were selected by
      participants from the full theme list (n = 9) based on perceived importance and
      feasibility: healthy product selection and display, store environment, and store
      outdoor appearance and cleanliness. Participants devised and presented a set of
      action steps to community leaders, and stakeholders have begun to incorporate
      these ideas into plans for the future of the healthy corner store network. Key
      elements of healthy corner stores were identified as positive, and other
      priorities, such as improvements to safety, exterior facades, and physical
      accessibility, may find common ground with other community development
      initiatives in Camden. Ultimately, this pilot study demonstrated the potential of
      citizen science to provide a systematic and data-driven process for public health
      stakeholders to authentically engage community residents in program evaluation.

PMID- 29632858
TI  - Combined in Vitro and in Silico Studies for the Anticholinesterase Activity and
      Pharmacokinetics of Coumarinyl Thiazoles and Oxadiazoles.
AB  - In a continuation of our previous work for the exploration of novel enzyme
      inhibitors, two new coumarin-thiazole 6(a-o) and coumarin-oxadiazole 11(a-h)
      hybrids have been designed and synthesized. All the compounds were characterized
      by 1H- and 13C-NMR spectroscopy and elemental analysis. New hybrid analogs were
      evaluated against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)
      in order to know their potential for the prevention of Alzheimer's disease (AD).
      In coumarinyl thiazole series, compound 6b was found as the most active member
      against AChE having IC50 value of 0.87 +/- 0.09 MUM, while the compound 6j
      revealed the same efficacy against BuChE with an IC50 value of 11.01 +/- 3.37
      MUM. In case of coumarinyl oxadiazole series, 11a was turned out to be the lead
      candidate against AChE with an IC50 value of 6.07 +/- 0.23 MUM, whereas compound
      11e was found significantly active against BuChE with an IC50 value of 0.15 +/-
      0.09 MUM. To realize the binding interaction of these compounds with AChE and
      BuChE, the molecular docking studies were performed. Compounds from coumarinyl
      thiazole series with potent AChE activity (6b, 6h, 6i, and 6k) were found to
      interact with AChE in the active site with MOE score of -10.19, -9.97, -9.68, and
      -11.03 Kcal.mol-1, respectively. The major interactions include hydrogen bonding,
      pi-pi stacking with aromatic residues, and interaction through water bridging.
      The docking studies of coumarinyl oxadiazole derivatives 11(a-h) suggested that
      the compounds with high anti-butyrylcholinesterase activity (11e, 11a, and 11b)
      provided MOE score of -9.9, -7.4, and -8.2 Kcal.mol-1, respectively, with the
      active site of BuChE building pi-pi stacking with Trp82 and water bridged
      interaction.

PMID- 29632859
TI  - Mechanisms for .[Formula: see text] and .OH Production on Flowerlike BiVO4
      Photocatalysis Based on Electron Spin Resonance.
AB  - Many studies have focused on the use of BiVO4 as a photocatalyst, but few have
      investigated the production of free radicals during the photocatalytic process.
      Following synthesis of flowerlike BiVO4 and characterization by X-ray diffraction
      (XRD), Raman spectroscopy, Scanning electron microscopy (SEM) Scanning electron
      microscopy (EDX), UV-Vis and XPS, we successfully prepared BiVO4. Then we used
      electron spin resonance (ESR) to determine the production and degradation of
      individual active free radicals, including the superoxide radical (.[Formula: see
      text]) and the hydroxyl radical (.OH). In the first experiment, we used ESR to
      detect the signals of free radicals (.[Formula: see text] and .OH) under varying
      oxygen conditions. The results shown that in addition to production by .[Formula:
      see text], .OH could also be produced by oxidation of h+ to OH-. In the next
      experiment, we detected .OH under varying pH to identify the result of the first
      experiment, and found that signal intensities increased with increasing pH,
      indicating the mechanism for .OH production. Finally, we conducted a trapping
      experiment to examine free radical degradation mechanisms. We identified .OH and
      h+ as the main active free radicals and showed the complete production about .OH.
      These results improve current knowledge of free radical production mechanisms,
      which can be used to enhance the photocatalytic performance of BiVO4.

PMID- 29632860
TI  - Discovery of Novel Bovine Viral Diarrhea Inhibitors Using Structure-Based Virtual
      Screening on the Envelope Protein E2.
AB  - Bovine viral diarrhea virus (BVDV) is a member of the genus Pestivirus within the
      family Flaviviridae. BVDV causes both acute and persistent infections in cattle,
      leading to substantial financial losses to the livestock industry each year. The
      global prevalence of persistent BVDV infection and the lack of a highly effective
      antiviral therapy have spurred intensive efforts to discover and develop novel
      anti-BVDV therapies in the pharmaceutical industry. Antiviral targeting of virus
      envelope proteins is an effective strategy for therapeutic intervention of viral
      infections. We performed prospective small-molecule high-throughput docking to
      identify molecules that likely bind to the region delimited by domains I and II
      of the envelope protein E2 of BVDV. Several structurally different compounds were
      purchased or synthesized, and assayed for antiviral activity against BVDV. Five
      of the selected compounds were active displaying IC50 values in the low- to mid
      micromolar range. For these compounds, their possible binding determinants were
      characterized by molecular dynamics simulations. A common pattern of interactions
      between active molecules and aminoacid residues in the binding site in E2 was
      observed. These findings could offer a better understanding of the interaction of
      BVDV E2 with these inhibitors, as well as benefit the discovery of novel and more
      potent BVDV antivirals.

PMID- 29632861
TI  - Compatibility of High-Moisture Storage for Biochemical Conversion of Corn Stover:
      Storage Performance at Laboratory and Field Scales.
AB  - Wet anaerobic storage of corn stover can provide a year-round supply of feedstock
      to biorefineries meanwhile serving an active management approach to reduce the
      risks associated with fire loss and microbial degradation. Wet logistics systems
      employ particle size reduction early in the supply chain through field-chopping
      which removes the dependency on drying corn stover prior to baling, expands the
      harvest window, and diminishes the biorefinery size reduction requirements. Over
      two harvest years, in-field forage chopping was capable of reducing over 60% of
      the corn stover to a particle size of 6 mm or less. Aerobic and anaerobic storage
      methods were evaluated for wet corn stover in 100 L laboratory reactors. Of the
      methods evaluated, traditional ensiling resulted in <6% total solid dry matter
      loss (DML), about five times less than the aerobic storage process and slightly
      less than half that of the anaerobic modified-Ritter pile method. To further
      demonstrate the effectiveness of the anaerobic storage, a field demonstration was
      completed with 272 dry tonnes of corn stover; DML averaged <5% after 6 months.
      Assessment of sugar release as a result of dilute acid or dilute alkaline
      pretreatment and subsequent enzymatic hydrolysis suggested that when anaerobic
      conditions were maintained in storage, sugar release was either similar to or
      greater than as-harvested material depending on the pretreatment chemistry used.
      This study demonstrates that wet logistics systems offer practical benefits for
      commercial corn stover supply, including particle size reduction during harvest,
      stability in storage, and compatibility with biochemical conversion of
      carbohydrates for biofuel production. Evaluation of the operational efficiencies
      and costs is suggested to quantify the potential benefits of a fully-wet biomass
      supply system to a commercial biorefinery.

PMID- 29632862
TI  - Metabolic Engineering of the Shikimate Pathway for Production of Aromatics and
      Derived Compounds-Present and Future Strain Construction Strategies.
AB  - The aromatic nature of shikimate pathway intermediates gives rise to a wealth of
      potential bio-replacements for commonly fossil fuel-derived aromatics, as well as
      naturally produced secondary metabolites. Through metabolic engineering, the
      abundance of certain intermediates may be increased, while draining flux from
      other branches off the pathway. Often targets for genetic engineering lie beyond
      the shikimate pathway, altering flux deep in central metabolism. This has been
      extensively used to develop microbial production systems for a variety of
      compounds valuable in chemical industry, including aromatic and non-aromatic
      acids like muconic acid, para-hydroxybenzoic acid, and para-coumaric acid, as
      well as aminobenzoic acids and aromatic alpha-amino acids. Further, many natural
      products and secondary metabolites that are valuable in food- and pharma-industry
      are formed outgoing from shikimate pathway intermediates. (Re)construction of
      such routes has been shown by de novo production of resveratrol, reticuline,
      opioids, and vanillin. In this review, strain construction strategies are
      compared across organisms and put into perspective with requirements by industry
      for commercial viability. Focus is put on enhancing flux to and through shikimate
      pathway, and engineering strategies are assessed in order to provide a guideline
      for future optimizations.

PMID- 29632863
TI  - Activators and Effectors of the Small G Protein Arf1 in Regulation of Golgi
      Dynamics During the Cell Division Cycle.
AB  - When eukaryotic cells divide, they must faithfully segregate not only the genetic
      material but also their membrane-bound organelles into each daughter cell. To
      assure correct partitioning of cellular contents, cells use regulatory mechanisms
      to verify that each stage of cell division has been correctly accomplished before
      proceeding to the next step. A great deal is known about mechanisms that regulate
      chromosome segregation during cell division, but we know much less about the
      mechanisms by which cellular organelles are partitioned, and how these processes
      are coordinated. The Golgi apparatus, the central sorting and modification
      station of the secretory pathway, disassembles during mitosis, a process that
      depends on Arf1 and its regulators and effectors. Prior to total disassembly, the
      Golgi ribbon in mammalian cells, composed of alternating cisternal stacks and
      tubular networks, undergoes fission of the tubular networks to produce individual
      stacks. Failure to carry out this unlinking leads to cell division arrest at late
      G2 prior to entering mitosis, an arrest that can be relieved by inhibition of
      Arf1 activation. The level of active Arf1-GTP drops during mitosis, due to
      inactivation of the major Arf1 guanine nucleotide exchange factor at the Golgi,
      GBF1. Expression of constitutively active Arf1 prevents Golgi disassembly, and
      leads to defects in chromosome segregation and cytokinesis. In this review, we
      describe recent advances in understanding the functions of Arf1 regulators and
      effectors in the crosstalk between Golgi structure and cell cycle regulation.

PMID- 29632864
TI  - Circulating Cell-Free DNA in Hepatocellular Carcinoma: Current Insights and
      Outlook.
AB  - Over the past decade, the advancements in massively parallel sequencing have
      provided a new paradigm in biomedical research to uncover the genetic basis of
      human diseases. Integration of 'omics information has begun transforming clinical
      management of cancer patients in terms of diagnostics and treatment options,
      giving rise to the era of precision medicine. Currently, nucleic acids for
      molecular profiling for patients diagnosed with hepatocellular carcinoma (HCC)
      are typically obtained from resected tumor materials or transplanted neoplastic
      liver and occasionally from biopsies. Given the intrinsic risks associated with
      such invasive procedures, circulating cell-free DNA (cfDNA) has been proposed as
      an alternative source for tumor DNA. Circulating cfDNA is a type of cell-free
      nucleic acid that derives from apoptotic, necrotic, as well as living eukaryotic
      cells. Importantly, the detection of abnormal forms of circulating cfDNA that
      originate from cancer cells provides a new tool for cancer detection, disease
      monitoring, and molecular profiling. Currently, cfDNA is beginning to be adopted
      into clinical practice as a non-invasive tool to monitor disease by tracking the
      evolution of disease-specific genetic alterations in several major cancer types.
      Moreover, cfDNA is demonstrating potential clinical value as a surrogate to
      assess the molecular makeup of tumors and to overcome the sampling biases
      inherent to intra-tumor genetic heterogeneity, especially in the metastatic
      setting. With the improvements in 'omics and molecular biology techniques,
      coupled with the increasing understanding in the molecular pathogenesis of
      cancer, it can be anticipated that the detection and analysis of cfDNA will
      become more specific and sensitive and thus enable cfDNA analysis to be used as a
      diagnostic aid in patients with early-stage disease and perhaps even in a
      screening setting. In this review, we provide an overview of the latest findings
      on the role and potential utility of cfDNA analysis in the diagnosis, management,
      and screening of HCC.

PMID- 29632865
TI  - Pregnancy and Cardiomyopathy After Anthracyclines in Childhood.
AB  - With advances in cancer therapy, there has been a remarkable increase in survival
      in children diagnosed with malignancies. Many of these children are treated with
      anthracyclines which are well known to cause cardiotoxicity. As more childhood
      cancer survivors reach childbearing age, many will choose to become pregnant. At
      this time, the factors associated with development of cardiomyopathy after
      anthracycline treatment are not clearly identified. It is possible that cardiac
      stress could predispose to cardiac deterioration in a patient with reduced
      functional reserve from prior anthracycline exposure. Pregnancy is one form of
      cardiovascular stress. The cardiac outcomes of pregnancy in childhood cancer
      survivors must be considered. In view of limited data, guidelines for pregnancy
      planning, management, and monitoring after cardiotoxic cancer therapy have not
      been established. This review summarizes the limited data available on the topic
      of pregnancy after anthracyclines in childhood.

PMID- 29632867
TI  - Comparison of Tracheal Wash and Bronchoalveolar Lavage Cytology in 154 Horses
      With and Without Respiratory Signs in a Referral Hospital Over 2009-2015.
AB  - Most equine lower respiratory diseases present as increased airway neutrophilia,
      which can be detected in tracheal wash (TW) or bronchoalveolar lavage fluid
      (BALF) cytology samples. The aim was to compare the TW and BALF results in a
      population of client-owned horses with and without clinical respiratory disease
      signs. A secondary aim was to determine the sensitivity (Se) and specificity (Sp)
      of TW and BALF neutrophilia in detecting respiratory disease. The cutoff values
      for neutrophils were also evaluated. Retrospective data from 154 horses of
      various breeds that had been subject to both TW and bronchoalveolar lavage (BAL)
      sampling at rest during 2009-2015 were used. The horses were divided into three
      groups based on the presenting signs, physical examination, and endoscopy mucus
      score. Neutrophil counts of >20% in TW and >5% in BAL were considered abnormal.
      Cytology results between groups, correlations between TW and BALF cell types, and
      tracheal mucus score were analyzed. Two graph receiving operating characteristic
      (ROC) curves of the neutrophil percentage values of TW and BALF were created to
      determine the optimal cutoff values and to calculate the diagnostic Se and Sp for
      diagnosing airway inflammation in horses with and without clinical respiratory
      signs. The Se and Sp of TW and BALF neutrophil percentages were further estimated
      using a two-test one-population Bayesian latent class model. The two tests showed
      substantial agreement, and only 17.5% of the horses were classified differently
      (healthy vs. diseased). The neutrophil percentage was found to correlate between
      TW and BALF. The Se and Sp of TW were generally higher than for BAL when
      estimated with area under the curve or Bayesian model. Cutoff values of 17.7% for
      TW and 7% for BALF were indicated by the ROCs. We conclude that TW is a more
      sensitive and specific method in our patient population. We suggest that the
      current neutrophil cutoff values of 20% for TW and 5% for BALF would still be
      appropriate to use in clinical diagnosis of airway inflammation. However, further
      studies with other cell types and in other populations are warranted to determine
      the best sampling method for individual horses.

PMID- 29632866
TI  - Cell Phenotype Transitions in Cardiovascular Calcification.
AB  - Cardiovascular calcification was originally considered a passive, degenerative
      process, however with the advance of cellular and molecular biology techniques it
      is now appreciated that ectopic calcification is an active biological process.
      Vascular calcification is the most common form of ectopic calcification, and
      aging as well as specific disease states such as atherosclerosis, diabetes, and
      genetic mutations, exhibit this pathology. In the vessels and valves, endothelial
      cells, smooth muscle cells, and fibroblast-like cells contribute to the formation
      of extracellular calcified nodules. Research suggests that these vascular cells
      undergo a phenotypic switch whereby they acquire osteoblast-like characteristics,
      however the mechanisms driving the early aspects of these cell transitions are
      not fully understood. Osteoblasts are true bone-forming cells and differentiate
      from their pluripotent precursor, the mesenchymal stem cell (MSC); vascular cells
      that acquire the ability to calcify share aspects of the transcriptional programs
      exhibited by MSCs differentiating into osteoblasts. What is unknown is whether a
      fully-differentiated vascular cell directly acquires the ability to calcify by
      the upregulation of osteogenic genes or, whether these vascular cells first de
      differentiate into an MSC-like state before obtaining a "second hit" that induces
      them to re-differentiate down an osteogenic lineage. Addressing these questions
      will enable progress in preventative and regenerative medicine strategies to
      combat vascular calcification pathologies. In this review, we will summarize what
      is known about the phenotypic switching of vascular endothelial, smooth muscle,
      and valvular cells.

PMID- 29632868
TI  - Detection of Risky Driving Behaviors in the Naturalistic Environment in Healthy
      Older Adults and Mild Alzheimer's Disease.
AB  - Analyzing naturalistic driving behavior recorded with in-car cameras is an
      ecologically valid method for measuring driving errors, but it is time intensive
      and not easily applied on a large scale. This study validated a semi-automated,
      computerized method using archival naturalistic driving data collected for
      drivers with mild Alzheimer's disease (AD; n = 44) and age-matched healthy
      controls (HC; n = 16). The computerized method flagged driving situations where
      safety concerns are most likely to occur (i.e., rapid stops, lane deviations,
      turns, and intersections). These driving epochs were manually reviewed and rated
      for error type and severity, if present. Ratings were made with a standardized
      scoring system adapted from DriveCam(r). The top eight error types were applied
      as features to train a logistic model tree classifier to predict diagnostic
      group. The sensitivity and specificity were compared among the event-based
      method, on-road test, and composite ratings of two weeks of recorded driving. The
      logistic model derived from the event-based method had the best overall accuracy
      (91.7%) and sensitivity (97.7%) and high specificity (75.0%) compared to the
      other methods. Review of driving situations where risk is highest appears to be a
      sensitive data reduction method for detecting cognitive impairment associated
      driving behaviors and may be a more cost-effective method for analyzing large
      volumes of naturalistic data.

PMID- 29632869
TI  - Excitatory Neuronal Responses of Ca2+ Transients in Interstitial Cells of Cajal
      in the Small Intestine.
AB  - Interstitial cells of Cajal (ICC) regulate smooth muscle excitability and
      motility in the gastrointestinal (GI) tract. ICC in the deep muscular plexus (ICC
      DMP) of the small intestine are aligned closely with varicosities of enteric
      motor neurons and thought to transduce neural responses. ICC-DMP generate Ca2+
      transients that activate Ca2+ activated Cl- channels and generate
      electrophysiological responses. We tested the hypothesis that excitatory
      neurotransmitters regulate Ca2+ transients in ICC-DMP as a means of regulating
      intestinal muscles. High-resolution confocal microscopy was used to image Ca2+
      transients in ICC-DMP within murine small intestinal muscles with cell-specific
      expression of GCaMP3. Intrinsic nerves were stimulated by electrical field
      stimulation (EFS). ICC-DMP exhibited ongoing Ca2+ transients before stimuli were
      applied. EFS caused initial suppression of Ca2+ transients, followed by escape
      during sustained stimulation, and large increases in Ca2+ transients after
      cessation of stimulation. Basal Ca2+ activity and the excitatory phases of Ca2+
      responses to EFS were inhibited by atropine and neurokinin 1 receptor (NK1)
      antagonists, but not by NK2 receptor antagonists. Exogenous ACh and substance P
      (SP) increased Ca2+ transients, atropine and NK1 antagonists decreased Ca2+
      transients. Neurokinins appear to be released spontaneously (tonic excitation) in
      small intestinal muscles and are the dominant excitatory neurotransmitters.
      Subcellular regulation of Ca2+ release events in ICC-DMP may be a means by which
      excitatory neurotransmission organizes intestinal motility patterns.

PMID- 29632870
TI  - Dopaminergic Drug Effects on Probability Weighting during Risky Decision Making.
AB  - Dopamine has been associated with risky decision-making, as well as with
      pathological gambling, a behavioral addiction characterized by excessive risk
      taking behavior. However, the specific mechanisms through which dopamine might
      act to foster risk-taking and pathological gambling remain elusive. Here we test
      the hypothesis that this might be achieved, in part, via modulation of subjective
      probability weighting during decision making. Human healthy controls (n = 21) and
      pathological gamblers (n = 16) played a decision-making task involving choices
      between sure monetary options and risky gambles both in the gain and loss
      domains. Each participant played the task twice, either under placebo or the
      dopamine D2/D3 receptor antagonist sulpiride, in a double-blind counterbalanced
      design. A prospect theory modelling approach was used to estimate subjective
      probability weighting and sensitivity to monetary outcomes. Consistent with
      prospect theory, we found that participants presented a distortion in the
      subjective weighting of probabilities, i.e., they overweighted low probabilities
      and underweighted moderate to high probabilities, both in the gain and loss
      domains. Compared with placebo, sulpiride attenuated this distortion in the gain
      domain. Across drugs, the groups did not differ in their probability weighting,
      although gamblers consistently underweighted losing probabilities in the placebo
      condition. Overall, our results reveal that dopamine D2/D3 receptor antagonism
      modulates the subjective weighting of probabilities in the gain domain, in the
      direction of more objective, economically rational decision making.

PMID- 29632872
TI  - A Conversation with Jas Pal Badyal.

PMID- 29632873
TI  - Battling a Deadly Bat Fungus.

PMID- 29632871
TI  - Brain Activity during Methamphetamine Anticipation in a Non-Invasive Self
      Administration Paradigm in Mice.
AB  - The ability to sense time and anticipate events is critical for survival. Learned
      responses that allow anticipation of the availability of food or water have been
      intensively studied. While anticipatory behaviors also occur prior to
      availability of regularly available rewards, there has been relatively little
      work on anticipation of drugs of abuse, specifically methamphetamine (MA). In the
      present study, we used a protocol that avoided possible CNS effects of stresses
      of handling or surgery by testing anticipation of MA availability in animals
      living in their home cages, with daily voluntary access to the drug at a fixed
      time of day. Anticipation was operationalized as the amount of wheel running
      prior to MA availability. Mice were divided into four groups given access to
      either nebulized MA or water, in early or late day. Animals with access to MA,
      but not water controls, showed anticipatory activity, with more anticipation in
      early compared to late day and significant interaction effects. Next, we explored
      the neural basis of the MA anticipation, using c-FOS expression, in animals
      euthanized at the usual time of nebulization access. In the dorsomedial
      hypothalamus (DMH) and orbitofrontal cortex (OFC), the pattern of c-FOS
      expression paralleled that of anticipatory behavior, with significant main and
      interaction effects of treatment and time of day. The results for the lateral
      septum (LS) were significant for main effects and marginally significant for
      interaction effects. These studies suggest that anticipation of MA is associated
      with activation of brain regions important in circadian timing, emotional
      regulation, and decision making.

PMID- 29632874
TI  - Lipoxygenases-Killers against Their Will?

PMID- 29632875
TI  - For CO2 Reduction, Hydrogen-Bond Donors Do the Trick.

PMID- 29632876
TI  - A DNA-Based Magnetic Sensor.

PMID- 29632877
TI  - Can Metal-Organic Framework Composites Contain the Water Contamination Crisis?

PMID- 29632879
TI  - Biodegradable Polymeric Materials in Degradable Electronic Devices.
AB  - Biodegradable electronics have great potential to reduce the environmental
      footprint of devices and enable advanced health monitoring and therapeutic
      technologies. Complex biodegradable electronics require biodegradable substrates,
      insulators, conductors, and semiconductors, all of which comprise the fundamental
      building blocks of devices. This review will survey recent trends in the
      strategies used to fabricate biodegradable forms of each of these components.
      Polymers that can disintegrate without full chemical breakdown (type I), as well
      as those that can be recycled into monomeric and oligomeric building blocks (type
      II), will be discussed. Type I degradation is typically achieved with engineering
      and material science based strategies, whereas type II degradation often requires
      deliberate synthetic approaches. Notably, unconventional degradable linkages
      capable of maintaining long-range conjugation have been relatively unexplored,
      yet may enable fully biodegradable conductors and semiconductors with
      uncompromised electrical properties. While substantial progress has been made in
      developing degradable device components, the electrical and mechanical properties
      of these materials must be improved before fully degradable complex electronics
      can be realized.

PMID- 29632878
TI  - Recent Development of Inorganic Nanoparticles for Biomedical Imaging.
AB  - Inorganic nanoparticle-based biomedical imaging probes have been studied
      extensively as a potential alternative to conventional molecular imaging probes.
      Not only can they provide better imaging performance but they can also offer
      greater versatility of multimodal, stimuli-responsive, and targeted imaging.
      However, inorganic nanoparticle-based probes are still far from practical use in
      clinics due to safety concerns and less-optimized efficiency. In this context, it
      would be valuable to look over the underlying issues. This outlook highlights the
      recent advances in the development of inorganic nanoparticle-based probes for
      MRI, CT, and anti-Stokes shift-based optical imaging. Various issues and
      possibilities regarding the construction of imaging probes are discussed, and
      future research directions are suggested.

PMID- 29632880
TI  - Rapid, Selective Heavy Metal Removal from Water by a Metal-Organic
      Framework/Polydopamine Composite.
AB  - Drinking water contamination with heavy metals, particularly lead, is a
      persistent problem worldwide with grave public health consequences. Existing
      purification methods often cannot address this problem quickly and economically.
      Here we report a cheap, water stable metal-organic framework/polymer composite,
      Fe-BTC/PDA, that exhibits rapid, selective removal of large quantities of heavy
      metals, such as Pb2+ and Hg2+, from real world water samples. In this work, Fe
      BTC is treated with dopamine, which undergoes a spontaneous polymerization to
      polydopamine (PDA) within its pores via the Fe3+ open metal sites. The PDA,
      pinned on the internal MOF surface, gains extrinsic porosity, resulting in a
      composite that binds up to 1634 mg of Hg2+ and 394 mg of Pb2+ per gram of
      composite and removes more than 99.8% of these ions from a 1 ppm solution,
      yielding drinkable levels in seconds. Further, the composite properties are well
      maintained in river and seawater samples spiked with only trace amounts of lead,
      illustrating unprecedented selectivity. Remarkably, no significant uptake of
      competing metal ions is observed even when interferents, such as Na+, are present
      at concentrations up to 14 000 times that of Pb2+. The material is further shown
      to be resistant to fouling when tested in high concentrations of common organic
      interferents, like humic acid, and is fully regenerable over many cycles.

PMID- 29632881
TI  - Development of an Efficacious, Semisynthetic Glycoconjugate Vaccine Candidate
      against Streptococcus pneumoniae Serotype 1.
AB  - Infections with Streptococcus pneumoniae are a major health burden.
      Glycoconjugate vaccines based on capsular polysaccharides (CPSs) successfully
      protect from infection, but not all pneumococcal serotypes are covered with equal
      potency. Marketed glycoconjugate vaccines induce low levels of functional
      antibodies against the highly invasive serotype 1 (ST1), presumably due to the
      obscuring of protective epitopes during chemical activation and conjugation to
      carrier proteins. Synthetic oligosaccharide antigens can be designed to carry
      linkers for site-selective protein conjugation while keeping protective epitopes
      intact. Here, we developed an efficacious semisynthetic ST1 glycoconjugate
      vaccine candidate. A panel of synthetic oligosaccharides served to reveal a
      critical role of the rare aminosugar, 2-acetamido-4-amino-2,4,6-trideoxy-d
      galactose (d-AAT), for ST1 immune recognition. A monovalent ST1 trisaccharide
      carrying d-AAT at the nonreducing end induced a strong antibacterial immune
      response in rabbits and outperformed the ST1 component of the multivalent
      blockbuster vaccine Prevenar 13, paving the way for a more efficacious vaccine.

PMID- 29632882
TI  - Shuttling Rates, Electronic States, and Hysteresis in a Ring-in-Ring Rotaxane.
AB  - The trisradical recognition motif between a 4,4'-bipyridinium radical cation and
      a cyclo-bis-4,4'-bipyridinium diradical dication has been employed previously in
      rotaxanes to control their nanomechanical and electronic properties. Herein, we
      describe the synthesis and characterization of a redox-active ring-in-ring
      [2]rotaxane BBR.8PF6 that employs a tetraradical variant of this recognition
      motif. A square-shaped bis-4,4'-bipyridinium cyclophane is mechanically
      interlocked around the dumbbell component of this rotaxane, and the dumbbell
      itself incorporates a smaller bis-4,4'-bipyridinium cyclophane into its
      covalently bonded structure. This small cyclophane serves as a significant
      impediment to the shuttling of the larger ring across the dumbbell component of
      BBR8+ , whereas reduction to the tetraradical tetracationic state BBR4(+*)
      results in strong association of the two cyclophanes driven by two radical
      pairing interactions. In these respects, BBR.8PF6 exhibits qualitatively similar
      behavior to its predecessors that interconvert between hexacationic and
      trisradical tricationic states. The rigid preorganization of two bipyridinium
      groups within the dumbbell of BBR.8PF6 confers, however, two distinct properties
      upon this rotaxane: (1) the rate of shuttling is reduced significantly relative
      to those of its predecessors, resulting in marked electrochemical hysteresis
      observed by cyclic voltammetry for switching between the BBR8+/BBR4(+*) states,
      and (2) the formally tetraradical form of the rotaxane, BBR4(+*) , exhibits a
      diamagnetic ground state, which, as a result of the slow shuttling motions within
      BBR4(+*) , has a long enough lifetime to be characterized by 1H NMR spectroscopy.

PMID- 29632883
TI  - Diverse Engineered Heme Proteins Enable Stereodivergent Cyclopropanation of
      Unactivated Alkenes.
AB  - Developing catalysts that produce each stereoisomer of a desired product
      selectively is a longstanding synthetic challenge. Biochemists have addressed
      this challenge by screening nature's diversity to discover enzymes that catalyze
      the formation of complementary stereoisomers. We show here that the same approach
      can be applied to a new-to-nature enzymatic reaction, alkene cyclopropanation via
      carbene transfer. By screening diverse native and engineered heme proteins, we
      identified globins and serine-ligated "P411" variants of cytochromes P450 with
      promiscuous activity for cyclopropanation of unactivated alkene substrates. We
      then enhanced their activities and stereoselectivities by directed evolution:
      just 1-3 rounds of site-saturation mutagenesis and screening generated enzymes
      that transform unactivated alkenes and electron-deficient alkenes into each of
      the four stereoisomeric cyclopropanes with up to 5,400 total turnovers and 98%
      enantiomeric excess. These fully genetically encoded biocatalysts function in
      whole Escherichia coli cells in mild, aqueous conditions and provide the first
      example of enantioselective, intermolecular iron-catalyzed cyclopropanation of
      unactivated alkenes.

PMID- 29632884
TI  - Defining the Structure of a Protein-Spherical Nucleic Acid Conjugate and Its
      Counterionic Cloud.
AB  - Protein-spherical nucleic acid conjugates (Pro-SNAs) are an emerging class of
      bioconjugates that have properties defined by their protein cores and dense shell
      of oligonucleotides. They have been used as building blocks in DNA-driven crystal
      engineering strategies and show promise as agents that can cross cell membranes
      and affect both protein and DNA-mediated processes inside cells. However, ionic
      environments surrounding proteins can influence their activity and conformational
      stability, and functionalizing proteins with DNA substantively changes the
      surrounding ionic environment in a nonuniform manner. Techniques typically used
      to determine protein structure fail to capture such irregular ionic
      distributions. Here, we determine the counterion radial distribution profile
      surrounding Pro-SNAs dispersed in RbCl with 1 nm resolution through in situ
      anomalous small-angle X-ray scattering (ASAXS) and classical density functional
      theory (DFT). SAXS analysis also reveals the radial extension of the DNA and the
      linker used to covalently attach the DNA to the protein surface. At the
      experimental salt concentration of 50 mM RbCl, Rb+ cations compensate ~90% of the
      negative charge due to the DNA and linker. Above 75 mM, DFT calculations predict
      overcompensation of the DNA charge by Rb+. This study suggests a method for
      exploring Pro-SNA structure and function in different environments through
      predictions of ionic cloud densities as a function of salt concentration, DNA
      grafting density, and length. Overall, our study demonstrates that solution X-ray
      scattering combined with DFT can discern counterionic distribution and
      submolecular features of highly charged, complex nanoparticle constructs such as
      Pro-SNAs and related nucleic acid conjugate materials.

PMID- 29632885
TI  - Resolving the Role of Lipoxygenases in the Initiation and Execution of
      Ferroptosis.
AB  - Lipoxygenases (LOXs) have been implicated as central players in ferroptosis, a
      recently characterized cell death modality associated with the accumulation of
      lipid hydroperoxides: the products of LOX catalysis. To provide insight on their
      role, human embryonic kidney cells were transfected to overexpress each of the
      human isoforms associated with disease, 5-LOX, p12-LOX, and 15-LOX-1, which
      yielded stable cell lines that were demonstrably sensitized to ferroptosis.
      Interestingly, the cells could be rescued by less than half of a diverse
      collection of known LOX inhibitors. Furthermore, the cytoprotective compounds
      were similarly potent in each of the cell lines even though some were clearly
      isoform-selective LOX inhibitors. The cytoprotective compounds were subsequently
      demonstrated to be effective radical-trapping antioxidants, which protect lipids
      from autoxidation, the autocatalytic radical chain reaction that produces lipid
      hydroperoxides. From these data (and others reported herein), a picture emerges
      wherein LOX activity may contribute to the cellular pool of lipid hydroperoxides
      that initiate ferroptosis, but lipid autoxidation drives the cell death process.

PMID- 29632886
TI  - Pendant Hydrogen-Bond Donors in Cobalt Catalysts Independently Enhance CO2
      Reduction.
AB  - The bioinspired incorporation of pendant proton donors into transition metal
      catalysts is a promising strategy for converting environmentally deleterious CO2
      to higher energy products. However, the mechanism of proton transfer in these
      systems is poorly understood. Herein, we present a series of cobalt complexes
      with varying pendant secondary and tertiary amines in the ligand framework with
      the aim of disentangling the roles of the first and second coordination spheres
      in CO2 reduction catalysis. Electrochemical and kinetic studies indicate that the
      rate of catalysis shows a first-order dependence on acid, CO2, and the number of
      pendant secondary amines, respectively. Density functional theory studies explain
      the experimentally observed trends and indicate that pendant secondary amines do
      not directly transfer protons to CO2, but instead bind acid molecules from
      solution. Taken together, these results suggest a mechanism in which
      noncooperative pendant amines facilitate a hydrogen-bonding network that enables
      direct proton transfer from acid to the activated CO2 substrate.

PMID- 29632887
TI  - A Compass at Weak Magnetic Fields Using Thymine Dimer Repair.
AB  - How birds sense the variations in Earth's magnetic field for navigation is poorly
      understood, although cryptochromes, proteins homologous to photolyases, have been
      proposed to participate in this magnetic sensing. Here, in electrochemical
      studies with an applied magnetic field, we monitor the repair of cyclobutane
      pyrimidine dimer lesions in duplex DNA by photolyase, mutants of photolyase, and
      a modified cryptochrome. We find that the yield of dimer repair is dependent on
      the strength and angle of the applied magnetic field even when using magnetic
      fields weaker than 1 gauss. This high sensitivity to weak magnetic fields depends
      upon a fast radical pair reaction on the thymines leading to repair. These data
      illustrate chemically how cyclobutane pyrimidine dimer repair may be used in a
      biological compass informed by variations in Earth's magnetic field.

PMID- 29632888
TI  - Nematic Order Imposes Molecular Weight Effect on Charge Transport in Conjugated
      Polymers.
AB  - Nematic order, in the bulk or at interfaces, is ubiquitous for semiflexible
      conjugated polymers. Nevertheless, the effect of liquid crystalline order on
      charge transport remains unclear. Using an analytical model, we demonstrate that
      nematic order leads to an enhancement in charge mobilities when compared to
      isotropic chains. Furthermore, we predict a quadratic dependence of the charge
      mobility on molecular weight of the chains. Analysis of the probability of
      forming hairpin defects also shows how the persistence length affects charge
      transport in conjugated polymers. We speculate that the prevalence of nematic
      order in conjugated polymers explains the reported increase in charge mobilities
      with molecular weight.

PMID- 29632889
TI  - Nonlinear fracture toughness measurement and crack propagation resistance of
      functionalized graphene multilayers.
AB  - Despite promising applications of two-dimensional (2D) materials, one major
      concern is their propensity to fail in a brittle manner, which results in a low
      fracture toughness causing reliability issues in practical applications. We show
      that this limitation can be overcome by using functionalized graphene multilayers
      with fracture toughness (J integral) as high as ~39 J/m2, measured via a
      microelectromechanical systems-based in situ transmission electron microscopy
      technique coupled with nonlinear finite element fracture analysis. The measured
      fracture toughness of functionalized graphene multilayers is more than two times
      higher than graphene (~16 J/m2). A linear fracture analysis, similar to that
      previously applied to other 2D materials, was also conducted and found to be
      inaccurate due to the nonlinear nature of the stress-strain response of
      functionalized graphene multilayers. A crack arresting mechanism of
      functionalized graphene multilayers was experimentally observed and identified as
      the main contributing factor for the higher fracture toughness as compared to
      graphene. Molecular dynamics simulations revealed that the interactions among
      functionalized atoms in constituent layers and distinct fracture pathways in
      individual layers, due to a random distribution of functionalized carbon atoms in
      multilayers, restrict the growth of a preexisting crack. The results inspire
      potential strategies for overcoming the relatively low fracture toughness of 2D
      materials through chemical functionalization.

PMID- 29632890
TI  - Geoelectrochemical CO production: Implications for the autotrophic origin of
      life.
AB  - Wachtershauser's proposal of the autotrophic origin of life theory and subsequent
      laboratory demonstrations of relevant organic reactions have opened a new gate
      for the exploration of the origin of life. However, this scenario remains
      controversial because, at present, it requires a high pressure of CO as a source
      of carbon and reducing energy, although CO must have been a trace C species on
      the Hadean Earth. We show that, simulating a geoelectrochemical environment in
      deep-sea hydrothermal fields, CO production with up to ~40% Faraday efficiency
      was attainable on CdS in CO2-saturated NaCl solution at <=-1 V (versus the
      standard hydrogen electrode). The threshold potential is readily generated in the
      H2-rich, high-temperature, and alkaline hydrothermal vents that were probably
      widespread on the early komatiitic and basaltic ocean crust. Thus,
      Wachtershauser's scenario starting from CO2 was likely to be realized in the
      Hadean ocean hydrothermal systems.

PMID- 29632891
TI  - Organic fertilizer as a vehicle for the entry of microplastic into the
      environment.
AB  - The contamination of the environment with microplastic, defined as particles
      smaller than 5 mm, has emerged as a global challenge because it may pose risks to
      biota and public health. Current research focuses predominantly on aquatic
      systems, whereas comparatively little is known regarding the sources, pathways,
      and possible accumulation of plastic particles in terrestrial ecosystems. We
      investigated the potential of organic fertilizers from biowaste fermentation and
      composting as an entry path for microplastic particles into the environment.
      Particles were classified by size and identified by attenuated total reflection
      Fourier transform infrared spectroscopy. All fertilizer samples from plants
      converting biowaste contained plastic particles, but amounts differed
      significantly with substrate pretreatment, plant, and waste (for example,
      household versus commerce) type. In contrast, digestates from agricultural energy
      crop digesters tested for comparison contained only isolated particles, if any.
      Among the most abundant synthetic polymers observed were those used for common
      consumer products. Our results indicate that depending on pretreatment, organic
      fertilizers from biowaste fermentation and composting, as applied in agriculture
      and gardening worldwide, are a neglected source of microplastic in the
      environment.

PMID- 29632892
TI  - Whole-genome sequencing of the blue whale and other rorquals finds signatures for
      introgressive gene flow.
AB  - Reconstructing the evolution of baleen whales (Mysticeti) has been problematic
      because morphological and genetic analyses have produced different scenarios.
      This might be caused by genomic admixture that may have taken place among some
      rorquals. We present the genomes of six whales, including the blue whale
      (Balaenoptera musculus), to reconstruct a species tree of baleen whales and to
      identify phylogenetic conflicts. Evolutionary multilocus analyses of 34,192
      genome fragments reveal a fast radiation of rorquals at 10.5 to 7.5 million years
      ago coinciding with oceanic circulation shifts. The evolutionarily enigmatic gray
      whale (Eschrichtius robustus) is placed among rorquals, and the blue whale genome
      shows a high degree of heterozygosity. The nearly equal frequency of conflicting
      gene trees suggests that speciation of rorqual evolution occurred under gene
      flow, which is best depicted by evolutionary networks. Especially in marine
      environments, sympatric speciation might be common; our results raise questions
      about how genetic divergence can be established.

PMID- 29632893
TI  - Implantation of hyaluronic acid hydrogel prevents the pain phenotype in a rat
      model of intervertebral disc injury.
AB  - Painful intervertebral disc degeneration is mediated by inflammation that
      modulates glycosylation and induces hyperinnervation and sensory sensitization,
      which result in discogenic pain. Hyaluronic acid (HA) used as a therapeutic
      biomaterial can reduce inflammation and pain, but the effects of HA therapy on
      glycosylation and pain associated with disc degeneration have not been previously
      determined. We describe a novel rat model of pain induced by intervertebral disc
      injury, with validation of the pain phenotype by morphine treatment. Using this
      model, we assessed the efficacy of HA hydrogel for the alleviation of pain,
      demonstrating that it reduced nociceptive behavior, an effect associated with
      down-regulation of nociception markers and inhibition of hyperinnervation.
      Furthermore, HA hydrogel altered glycosylation and modulated key inflammatory and
      regulatory signaling pathways, resulting in attenuation of inflammation and
      regulation of matrix components. Our results suggest that HA hydrogel is a
      promising clinical candidate for the treatment of back pain caused by degenerated
      discs.

PMID- 29632894
TI  - A low-barrier hydrogen bond mediates antibiotic resistance in a noncanonical
      catalytic triad.
AB  - One group of enzymes that confer resistance to aminoglycoside antibiotics through
      covalent modification belongs to the GCN5-related N-acetyltransferase (GNAT)
      superfamily. We show how a unique GNAT subfamily member uses a previously
      unidentified noncanonical catalytic triad, consisting of a glutamic acid, a
      histidine, and the antibiotic substrate itself, which acts as a nucleophile and
      attacks the acetyl donor molecule. Neutron diffraction studies allow for
      unambiguous identification of a low-barrier hydrogen bond, predicted in canonical
      catalytic triads to increase basicity of the histidine. This work highlights the
      role of this unique catalytic triad in mediating antibiotic resistance while
      providing new insights into the design of the next generation of aminoglycosides.

PMID- 29632895
TI  - The Warrior Wellness Study: A Randomized Controlled Exercise Trial for Older
      Veterans with PTSD.
AB  - Posttraumatic stress disorder (PTSD) affects up to 30% of military veterans.
      Older veterans, many of whom have lived with PTSD symptoms for several decades,
      report a number of negative health outcomes. Despite the demonstrated benefits of
      regular exercise on physical and psychological health, no studies have explored
      the impact of exercise in older veterans with PTSD. This paper describes the
      development, design, and implementation of the Warrior Wellness exercise pilot
      study for older veterans with PTSD. Veterans aged >=60 with a Diagnostic and
      Statistical Manual of Mental Disorders (DSM-V) diagnosis of PTSD will be
      recruited and randomized to (a) Warrior Wellness, a 12-week supervised, facility
      based exercise intervention, or (b) usual care for 12 weeks. Warrior Wellness is
      a theory- and evidence-based behavioral intervention that involves 3 sessions per
      week of multi-component exercise training that targets strength, endurance,
      balance, and flexibility. Warrior Wellness focuses on satisfaction with outcomes,
      self-efficacy, self-monitoring, and autonomy. Factors associated with program
      adherence, defined as the number of sessions attended during the 12 weeks, will
      be explored. Primary outcomes include PTSD symptoms and cardiovascular endurance,
      assessed at baseline and 12 weeks. Compared to those in usual care, it is
      hypothesized that those in the Warrior Wellness condition will improve on these
      efficacy outcomes. The Warrior Wellness study will provide evidence on whether a
      short-term exercise intervention is feasible, acceptable, and effective among
      older veterans with PTSD, and explore factors associated with program adherence.
      ClinicalTrials.gov Identifier: NCT02295995.

PMID- 29632896
TI  - Increasing women's access to skilled pregnancy care to reduce maternal and
      perinatal mortality in rural Edo State, Nigeria: a randomized controlled trial.
AB  - Background: Nigeria presently has the second highest absolute number of maternal
      deaths and perinatal deaths (stillbirth and neonatal deaths) in the world. The
      country accounts for up to 14% of global maternal deaths and is second only to
      India in the number of women who die during childbirth. Although all parts of the
      country are worsened by these staggering statistics, several lines of evidence
      show that most maternal, and perinatal deaths occur in the north-east and north
      west geo-political zones where women have limited access to evidence-based
      maternal and neonatal health services. The proposed project intends to identify
      the demand and supply factors that prevent women from using PHCs for maternal and
      early new-born care in Nigeria, and to test innovative and community relevant
      interventions for improving women's access to PHC services, and thus, ultimately,
      to prevent maternal and perinatal deaths. Methods: An open-labelled, randomized
      controlled trial will is carried out in two local government areas selected based
      on three criteria (i) maternal mortality rates (ii) PHC utilization rates and
      (iii) and geographic localization. The study will be conducted over 54-months in
      six communities, with PHCs in six communities of similar status serving as
      control sites. Surveys about quality of care and maternal health services
      utilization will be carried out at baseline, at midterm and at end of the project
      to test the effectiveness of the intervention, alongside conventional
      epidemiological measures of maternal and perinatal mortality. Ethical approval
      for the study has been granted (reference no. NHREC/01/01/2007). The findings
      will be published in compliance with reporting guidelines for randomized
      controlled trials. Discussion: The current Federal Government in Nigeria has
      identified PHC as its main strategy for increasing access to health in Nigeria.
      However, despite numerous efforts, there are persisting concerns that there is
      currently no scientific evidence on which to base the improvement of PHCs. The
      results of this study will identify barriers in the use of PHCs and will provide
      scientific evidence for effective and innovative interventions for improving PHCs
      that can be rolled out throughout the country. Trial registration: Clinical
      Trials.gov NCT02643953.

PMID- 29632897
TI  - Evaluation of Photochemistry Reaction Kinetics to Pattern Bioactive Proteins on
      Hydrogels for Biological Applications.
AB  - Bioactive signals play many important roles on cell function and behavior. In
      most biological studies, soluble biochemical cues such as growth factors or
      cytokines are added directly into the media to maintain and/or manipulate cell
      activities in vitro. However, these methods cannot accurately mimic certain in
      vivo biological signaling motifs, which are often immobilized to extracellular
      matrix and also display spatial gradients that are critical for tissue
      morphology. Besides biochemical cues, biophysical properties such as substrate
      stiffness can influence cell behavior but is not easy to manipulate under
      conventional cell culturing practices. Recent development in photocrosslinkable
      hydrogels provides new tools that allow precise control of spatial biochemical
      and biophysical cues for biological applications, but doing so requires a
      comprehensive study on various hydrogel photochemistry kinetics to allow thorough
      photocrosslink reaction while maintain protein bioactivities at the same time. In
      this paper, we studied several photochemistry reactions and evaluate key
      photochemical parameters, such as photoinitiators and ultra-violet (UV) exposure
      times, to understand their unique contributions to undesired protein damage and
      cell death. Our data illustrates the retention of protein function and minimize
      of cell health during photoreactions requires careful selection of photoinitiator
      type and concentration, and UV exposure times. We also developed a robust method
      based on thiol-norbornene chemistry for independent control of hydrogel stiffness
      and spatial bioactive patterns. Overall, we highlight a class of bioactive
      hydrogels to stiffness control and site specific immobilized bioactive
      proteins/peptides for the study of cellular behavior such as cellular attraction,
      repulsion and stem cell fate.

PMID- 29632899
TI  - Editorial - Delivering and transforming, but many questions and challenges
      remain.
AB  - Acute Medicine remains a specialty in its infancy and, as such, faces many
      challenges associated with developing new ways of working. As the Society for
      Acute Medicine celebrates its 18th birthday the extraordinary role of Acute
      Medicine in both maintaining and indeed enhancing the care and welfare of
      patients is increasingly evident. However, scepticism still persists among some
      colleagues with regards to its effectiveness - a perception heightened by the
      difficult environment that currently pervades in acute and emergency care in the
      UK which mirrors the experience of many countries internationally.

PMID- 29632898
TI  - LIFETIME PHYSICAL INACTIVITY IS ASSOCIATED WITH LUNG CANCER RISK AND MORTALITY.
AB  - INTRODUCTION: Investigations of the independent associations of physical
      inactivity with cancer endpoints have been mounting in the epidemiological
      literature, in part due to the high prevalence of physical inactivity among
      cancer patients and to evidence that inactivity associates with carcinogenesis
      via pathways independent of obesity. Yet, physical inactivity is not currently
      recognized as a well-established risk or prognostic factor for lung cancer. As
      such, we examined the associations of lifetime physical inactivity with lung
      cancer risk and mortality in a hospital-based, case-control study. PRESENTATION
      OF CASE: Materials and Methods: The analyses included data from 660 lung cancer
      patients and 1335 matched cancer-free controls. Multivariable logistic regression
      analyses were utilized to assess the association between lifetime physical
      inactivity and lung cancer risk, and Cox proportional hazards models were
      utilized to estimate the association between lifetime physical inactivity and
      mortality among lung cancer cases.Results: We observed a significant positive
      association between lifetime physical inactivity and lung cancer risk: [Odds
      ratio (OR)=2.23, 95% confidence interval (CI): 1.77-2.81]; the association
      remained significant among never smokers (OR=3.00, 95% CI:1.33-6.78) and non
      smokers (OR=2.33, 95% CI: 1.79-3.02). We also observed a significant positive
      association between lifetime physical inactivity and lung cancer mortality
      [Hazard ratio (HR)=1.40, 95% CI: 1.14-1.71]; the association remained significant
      in non-smokers (HR=1.51, 95% CI: 1.16-1.95). DISCUSSION/CONCLUSION: These data
      add to the body of evidence suggesting that physical inactivity is an independent
      risk and prognostic factor for cancer. Additional research utilizing
      prospectively collected data is needed to substantiate the current findings.

PMID- 29632900
TI  - A photoluminescence "switch-on" nanosensor composed of nitrogen and sulphur co
      doped carbon dots and gold nanoparticles for discriminative detection of
      glutathione.
AB  - Biological thiols play a key role in biological processes and are involved in a
      variety of diseases. The discriminative detection of biological thiols is still
      challenging. In this contribution, a platform, an energy transfer-based quenching
      system composed of nitrogen and sulphur co-doped carbon dots (N, S-CDs) and gold
      nanoparticles (AuNPs), was established to discriminate glutathione (GSH) from
      other competitive biothiols including cysteine (Cys) and homocysteine (Hcy) based
      on a photoluminescence (PL) "switch-on" signal readout. The presence of GSH can
      encapsulate AuNPs in priority because of the strong affinity towards AuNPs and
      the steric hindrance effect of GSH, leaving little chance for the N, S-CDs
      binding on the surface of AuNPs and thus resulting in the PL recovery of N, S
      CDs. Compared with the nitrogen-doped carbon dots (N-CDs), the N, S-CDs can
      enhance 10 times sensitivity for the designed PL "switch-on" sensing strategy.
      The proposed method has a detection limit of 3.6 nM and can be successfully
      applied for the detection of GSH in human serum.

PMID- 29632901
TI  - A narrow open tubular column for high efficiency liquid chromatographic
      separation.
AB  - We report a great feature of open tubular liquid chromatography when it is run
      using an extremely narrow (e.g., 2 MUm inner diameter) open tubular column: more
      than 10 million plates per meter can be achieved in less than 10 min and under an
      elution pressure of ca. 20 bar. The column is coated with octadecylsilane and
      both isocratic and gradient separations are performed. We reveal a focusing
      effect that may be used to interpret the efficiency enhancement. We also
      demonstrate the feasibility of using this technique for separating complex
      peptide samples. This high-resolution and fast separation technique is promising
      and can lead to a powerful tool for trace sample analysis.

PMID- 29632902
TI  - Polyelectrolyte complex films influence the formation of polycrystalline micro
      structures.
AB  - Silica-carbonate biomorphs are inorganic materials composed of thousands of
      crystalline nanorods that assemble complex morphologies such as helices, vessels,
      and sheets. We investigate the effect on biomorph crystallization of
      polyelectrolyte complex films that are prepared using the layer-by-layer
      deposition technique and post-processed to obtain three stable, chemically
      distinct films. Biomorph growth on poly(diallyldimethylammonium)-dominated
      substrates (cationic) shows polycrystalline helical and sheet structures bounded
      by large witherite prisms. Crystallization on poly(styrenesulfonate)-dominated
      (anionic) and stoichiometric substrates follows a qualitatively different
      pathway. We observe islands of radial mineral films that over several days extend
      at a remarkably constant velocity of 0.48 MUm h-1 and eventually mineralize the
      whole substrate. Our work opens exciting avenues for the use of polyelectrolyte
      films as tunable substrates for biomimetic crystallization.

PMID- 29632903
TI  - Self-trapping relaxation decay investigated by time-resolved photoelectron
      spectroscopy.
AB  - The present work combines time-resolved photoelectron spectroscopy on isolated
      species with high-level data processing to address an issue which usually
      pertains to materials science: the electronic relaxation dynamics towards the
      formation of a self-trapped exciton (STE). Such excitons are common excited
      states in ionic crystals, silica and rare gas matrices. They are associated with
      a strong local deformation of the matrix. Argon clusters were taken as a model.
      They are excited initially to a Wannier exciton at 14 eV and their evolution
      towards the formation of an STE has showed an unusual type of vibronic relaxation
      where the electronic excitation of the cluster decreases linearly as a function
      of time with a 0.59 +/- 0.06 eV ps-1 rate. The decay was followed for 3.0 ps, and
      the STE formation occurred in ~5.1 +/- 0.7 ps.

PMID- 29632904
TI  - Conformational sampling of the intrinsically disordered dsRBD-1 domain from
      Arabidopsis thaliana DCL1.
AB  - DCL1 is the ribonuclease that carries out miRNA biogenesis in plants. Substrate
      pri-miRNA recognition by DCL1 requires two double stranded RNA binding domains
      located at the C-terminus of the protein. We have previously shown that the first
      of these domains, DCL1-A, is intrinsically disordered and folds upon binding pri
      miRNA. Integrating NMR and SAXS data, we study here the conformational landscape
      of free DCL1-A through an ensemble description. Our results reveal that secondary
      structure elements, corresponding to the folded form of the protein, are
      transiently populated in the unbound state. The conformation of one of the dsRNA
      binding regions in the free protein shows that, at a local level, RNA recognition
      proceeds through a conformational selection mechanism. We further explored the
      stability of the preformed structural elements via temperature and urea
      destabilization. The C-terminal helix is halfway on the folding pathway in free
      DCL1-A, constituting a potential nucleation site for the final folding of the
      protein. In contrast, the N-terminal helix adopts stable non-native structures
      that could hinder the correct folding of the protein in the absence of RNA. This
      description of the unfolded form allows us to understand details of the mechanism
      of binding-induced folding of the protein.

PMID- 29632905
TI  - Interactions of vanadium(iv) with amidoxime ligands: redox reactivity.
AB  - The use of amidoxime-functionalized polymer fibers as a sorbent for uranium has
      attracted recent interest for the extraction of uranium from seawater. Vanadium
      is one of the main competing ions for uranium sorption as V(v) species, however,
      vanadium is also present as V(iv) in seawater. In the present study, the
      interactions of V(iv) with amidoxime and similar ligands were explored. Attempts
      were made to synthesize V(iv) complexes of glutaroimide-dioxime, a molecular
      analogue of polymer sorbents. However, V(iv) was found to react irreversibly with
      glutaroimide-dioxime and other oxime groups, oxidizing to the V(v) oxidation
      state. We have explored the reactions and propose mechanisms, as well as
      characterized the redox behavior of the vanadium-glutaroimide-dioxime complex.

PMID- 29632906
TI  - Simple preparation and highly selective detection of silver ions using an
      electrochemical sensor based on sulfur-doped graphene and a 3,3',5,5'
      tetramethylbenzidine composite modified electrode.
AB  - A novel electrochemical sensor based on sulfur (S)-doped graphene (S-Gr) and a
      3,3',5,5'-tetramethylbenzidine (TMB) composite (S-Gr-TMB) modified glassy carbon
      (GCE) electrode for highly selective quantitative detection of silver ions (Ag+)
      were fabricated. The S-Gr-TMB composite was first prepared via electrostatic
      interaction between TMB and S-Gr and then, the composite was coated on the
      surface of GCE. The resultant S-Gr-TMB/GCE electrode showed a significant
      voltammetric response to Ag+ at 0.3 V vs. Ag/AgCl due to the synergistic effect
      of S-Gr and TMB. The sensor showed good linearity from 50 MUM to 400 MUM with a
      detection limit of 2.15 MUM towards the determination of Ag+. In addition, after
      the addition of Fe3+ and other metal ions, including Al3+, Ca2+, Cd2+, Co2+,
      Cu2+, K+, Mg2+, Na+, Ni2+, Pb2+ and Zn2+, in the same concentration, the current
      signal remained almost unchanged, revealing that the proposed electrochemical
      sensor exhibited a high selectivity for Ag+, which solves the nonselective
      problem of TMB as a spectral probe. This enhanced detection performance is
      attributed to two factors: (1) S-Gr has excellent electrical conductivity; (2)
      the coupling interactions between Ag-S are speculated to result in strengthened
      enrichment for Ag and good selective performance.

PMID- 29632907
TI  - Stereodivergent trifluoromethylation of N-sulfinylimines by fluoroform with
      either organic-superbase or organometallic-base.
AB  - Here we have successfully demonstrated the first stereodivergent direct
      nucleophilic trifluoromethylation of N-sulfinylimines using the potent greenhouse
      gas "HFC-23, fluoroform" with an organic-superbase or an organometallic-base in
      high yields and selectivity.

PMID- 29632908
TI  - DNA-based nanoscaffolds as vehicles for 5-fluoro-2'-deoxyuridine oligomers in
      colorectal cancer therapy.
AB  - Fluoropyrimidines, such as 5-fluorouracil (5-FU) and related prodrugs, are
      considered one of the most successful agents in the treatment of colorectal
      cancer, yet poor specificity and tumor cell resistance remain the major limiting
      bottlenecks. Here, we exploited for the first time the ability of two DNA
      nanoscaffolds, a DNA tetrahedron (Td) and rectangle DNA origami, to incorporate 5
      fluoro-2'-deoxyuridine (FdUn) oligomers. In addition, cholesterol moieties were
      synthetically attached to Td and DNA origami staples to enhance cellular uptake.
      DNA nanostructures functionalized with FdUn exhibited an enhanced cytotoxicity
      and higher ability to trigger apoptosis in colorectal cancer cells relative to
      conventional 5-FU and FdU, especially having cholesterol as an internalization
      helper. The cholesterol content mostly correlates with the increase of the FdUn
      nanostructure cytotoxicity. DNA nanoscaffolds bearing FdUn were able to
      circumvent the low sensitivity of colorectal cancer cells towards 5-FU. Both DNA
      nanostructures attained a comparable cytotoxic effect yet Td displays higher
      antiproliferative action. The ability to reduce the proliferation of cancer cells
      is mainly related to the concentration of DNA nanostructures. The present work
      suggests that self-assembled DNA nanoparticles are privileged vehicles for
      delivering fluoropyrimidines, opening new avenues to the development of promising
      therapeutics for cancer treatment.

PMID- 29632909
TI  - Raspberry anthocyanin consumption prevents diet-induced obesity by alleviating
      oxidative stress and modulating hepatic lipid metabolism.
AB  - Evidence indicates that raspberries have beneficial effects on chronic diseases.
      The objective of this study was to examine the beneficial effects of raspberry
      anthocyanin (RA) on high fat diet-induced obesity and investigate the underlying
      molecular mechanism. C57BL/6 mice were administered a low-fat diet, high-fat
      diet, and high-fat diet supplemented with RA at a dose of 200 mg kg-1 of food for
      12 weeks. It was found that RA reduced the body weight gain by 63.7%.
      Furthermore, RA significantly elevated serum superoxide dismutase (SOD) and
      glutathione peroxidase (GSH-PX) activities and fecal butyric acid level,
      remarkably reduced the serum and hepatic lipid profiles, and markedly down
      regulated the expression of the tumor necrosis factor alpha (TNFalpha),
      interleukin-6 (IL-6), and nuclear factor kappaB (NF-kappaB) genes. Metabolomics
      analysis conducted using gas chromatography time-of-flight mass spectrometry (GC
      TOF/MS) indicated that RA administration promoted the recovery of metabolites
      involved in glycerophospholipid metabolism, insulin signaling pathway, and
      glutathione metabolism in the livers of obese mice. These findings suggest that
      RA may ameliorate diet-induced obesity by alleviating oxidative stress and
      modulating lipid metabolism.

PMID- 29632910
TI  - Intramolecular vibrational energy redistribution in HCCCH2X (X = Cl, Br, I)
      measured by femtosecond pump-probe experiments in a hollow waveguide.
AB  - From the analysis of high resolution overtone spectra it is well established that
      intramolecular vibrational energy redistribution (IVR) from an initially excited
      CH-stretching vibration is strongly influenced by its chemical environment. Due
      to a pronounced Fermi resonance between the CH-stretching and CH-bending
      vibrations a vibrational energy redistribution on the subpicosecond time scale
      (~100 fs) is found for alkyl (sp3) CH-chromophores, whereas this doorway for
      energy flow is blocked for the acetylenic (sp) CH-stretching vibration because of
      the much lower CH-bending frequency. From the analysis of the high resolution
      spectra lifetimes for the initial CH-vibrational excitation of 10-100 ps or
      longer have been derived. In the present work we have investigated the IVR
      process for HCCCH2Br, HCCCH2Cl, and HCCCH2I after excitation of the first
      overtone of the CH-stretching vibration of the CH2X- and the CCH-group by time
      resolved femtosecond pump-probe experiments in a hollow waveguide. For HCCCH2Br
      and HCCCH2Cl a clearly different IVR behavior was found for the two different
      chemical environments. For the excitation of the alkyl CH-chromophore very fast
      initial relaxation times were found together with a slower relaxation process
      with tau2 = 15-40 ps, whereas for the acetylenic CH-stretching vibration a
      relaxation time tau3 = 70-200 ps has been determined. For HCCCH2I also for the
      excitation of the CCH-group a relatively fast relaxation process with a time
      constant tau2 = 6 ps could be identified which might result from a not yet
      identified strong vibrational coupling between the excited first overtone of the
      acetylenic CH-stretching vibrations with a combination state including the CI
      stretching vibration.

PMID- 29632912
TI  - Isomeric structures of isolated ammonium nitrate and its hydrogenated species
      identified through PES experiments and DFT calculations.
AB  - Anion photoelectron spectroscopic (PES) experiments in conjunction with density
      functional theory (DFT) calculations shed light on the electronic and geometric
      structures of gas phase, isolated ammonium nitrate related anionic species, as
      well as their hydrogenated species with up to five added hydrogens. These species
      are directly generated by laser ablation and cooled in a supersonic expansion.
      Their vertical detachment energies (VDE: Eneutral - Eanion, both at the anionic
      geometry) are experimentally determined and the corresponding anionic structures
      are characterized and assigned through calculations. Based on the experimentally
      evaluated calculation algorithm, the corresponding neutral structures are also
      determined. The parent anionic species exists as (NH2OH.HONO)- in the gas phase
      with the extra electron valence bound. Crystal structure anion NH4NO3- is not
      present in our experiments, as within this structure the extra electron is dipole
      bound (electron affinity ~ 0 eV). The isomerization must therefore occur for
      ammonium nitrate upon capturing an extra electron or during the laser ablation
      process itself. The ammonium nitrate anion is apparently a very reactive species.
      The calculated global minimum for the isolated parent neutral species has an
      HNO3.NH3 structure, different from the crystal structure in the bulk phase. The
      hydrogenated cluster anions can evolve from the parent (NH2OH.HONO)- species and
      exhibit moieties, which bind together as a single unit through interactions
      between noncovalently bonded species and are stable on the experimental
      timescale. The hydrogenation process forms stable moieties in the cluster anions,
      including water (H2O), nitroxyl (HNO), ammonia (NH3), or (HNOH). The calculated
      global minimum structures for hydrogenated cluster neutrals (NH4NO3 + nH, n =
      1,...,5) contain ammonia and water, along with stable moieties (HONO, NO, and
      HNO). These stable moieties, along with intermediate species NO2H2 and ONH2,
      offer new insights into the behavior of ammonium nitrate energetic materials.

PMID- 29632913
TI  - Selective trapping of CO2 gas and cage occupancy in CO2-N2 and CO2-CO mixed gas
      hydrates.
AB  - Hydrate-based CO2 trapping from CO2-N2 and CO2-CO gas mixtures is shown by Raman
      spectroscopy - the results are of interest for new separation and capture
      technology. A better trapping efficiency is measured for low CO2 concentrations
      and N2-based gas mixtures. Moreover, it is observed that CO molecules would
      impede hydrate formation from ice when a CO-enriched gas mixture is considered.

PMID- 29632911
TI  - Structural and stereochemical diversity in prenylated indole alkaloids containing
      the bicyclo[2.2.2]diazaoctane ring system from marine and terrestrial fungi.
AB  - Covering: up to February 2017 Various fungi of the genera Aspergillus,
      Penicillium, and Malbranchea produce prenylated indole alkaloids possessing a
      bicyclo[2.2.2]diazaoctane ring system. After the discovery of distinct
      enantiomers of the natural alkaloids stephacidin A and notoamide B, from A.
      protuberus MF297-2 and A. amoenus NRRL 35660, another fungi, A. taichungensis,
      was found to produce their diastereomers, 6-epi-stephacidin A and versicolamide
      B, as major metabolites. Distinct enantiomers of stephacidin A and 6-epi
      stephacidin A may be derived from a common precursor, notoamide S, by enzymes
      that form a bicyclo[2.2.2]diazaoctane core via a putative intramolecular hetero
      Diels-Alder cycloaddition. This review provides our current understanding of the
      structural and stereochemical homologies and disparities of these alkaloids.
      Through the deployment of biomimetic syntheses, whole-genome sequencing, and
      biochemical studies, a unified biogenesis of both the dioxopiperazine and the
      monooxopiperazine families of prenylated indole alkaloids constituted of
      bicyclo[2.2.2]diazaoctane ring systems is presented.

PMID- 29632914
TI  - The halogen effect on the 13C NMR chemical shift in substituted benzenes.
AB  - Recent research [Chem. Sci., 2017, 8, 6570-6576] showed for R-substituted
      benzenes with R = NH2, NO2 that the substitution effects on the 13C NMR chemical
      shifts are correlated with changes in the sigma-bonding framework and do not
      follow directly the electron-donating or -withdrawing effects on the pi orbitals.
      In the present work we extend the study to halogen (X = F, Cl, Br or I)
      substituted R-benzenes. The effect of X and R groups on 13C NMR chemical shifts
      in X-R-benzenes are investigated by density functional calculations and localized
      molecular orbital analyses. Deshielding effects caused by the X atom on the
      directly bonded carbon nucleus are observed for F and Cl derivatives due to a
      paramagnetic coupling between occupied pi orbitals and unoccupied antibonding
      orbitals. The SO coupling plays an important role in the carbon magnetic
      shielding of Br and I derivatives, as is well known, and the nature of X also
      modulates the 13C paramagnetic shielding contributions. Overall, the X and R
      substituent effects are approximately additive.

PMID- 29632915
TI  - Surfactant-free one-pot synthesis of CeO2, TiO2 and Ti@Ce oxide nanoparticles for
      the ultrafast removal of Cr(vi) from aqueous media.
AB  - Cerium oxide (CeO2), titanium oxide (TiO2) and titanium oxide impregnated with
      cerium oxide (Ti@Ce oxide) nanoparticles were synthesized using a simple one-pot
      surfactant-free method. The synthesized adsorbents were tested against the
      removal of Cr(vi) from aqueous medium. Comprehensive characterization methods
      like BET, XRD, SEM, EDAX, HR-TEM, SAED, HR-XPS and FT-IR were performed at
      different stages of the adsorption process and synthesis. A N2-BET study revealed
      the large surface area (268 m2 g-1) and pore size (6.8 nm) of CeO2 nanoparticles,
      which decreased after impregnation of titania. An XRD study demonstrated the
      phase transformation of TiO2 from the anatase phase to the rutile phase after the
      impregnation with CeO2 by lowering the phase transformation temperature from >550
      degrees C to 400  degrees C. Ti0.3@Ce0.7 oxide nanoparticles showed 81% removal
      of Cr(vi) within 2.5 min of initiating the adsorption process while more than 92%
      removal of Cr(vi) was achieved within 10 min of adsorption. A HR-XPS study
      indicated the dual oxidation states of ceria and titania metals, which helped to
      convert the more toxic Cr(vi) ions to less toxic Cr(iii) ions during the
      adsorption process. The adsorption pattern depicted the monolayer behavior of
      Cr(vi) obeying the Redlich-Peterson isotherm and followed pseudo second-order
      kinetics. An intraparticle diffusion model disclosed the surface and pore
      resistance diffusion of Cr(vi) on the surface of adsorbents.

PMID- 29632916
TI  - Correction: A luminescent bimetallic iridium(iii) complex for ratiometric
      tracking intracellular viscosity.
AB  - Correction for 'A luminescent bimetallic iridium(iii) complex for ratiometric
      tracking intracellular viscosity' by Fengyu Liu et al., Chem. Commun., 2018, 54,
      1371-1374.

PMID- 29632917
TI  - Recent advances in spirocyclization of indole derivatives.
AB  - Spiroindolines and spiroindoles are an important class of spirocyclic compounds
      present in a wide range of pharmaceuticals and biologically important natural
      alkaloids. Various spiroindolines and spiroindoles possess versatile reactivity
      which enables them to act as precursors for other privileged heterocycles. In
      view of the importance of this scaffold, many researchers focused their efforts
      to develop facile and mild synthetic methods for spirocyclization of indoles.
      However, the synthesis of spiroindolines and spiroindoles is known to be
      difficult due to rapid 1,2-migration to restore aromaticity. This review aims to
      briefly discuss the latest developments to access highly functionalized
      spiroindolines and spiroindoles to stimulate further research in the field to
      find new and efficient methodologies for accessing new spiroindolines and
      spiroindoles.

PMID- 29632918
TI  - Quantum-dot light-emitting diodes with a perfluorinated ionomer-doped copper
      nickel oxide hole transporting layer.
AB  - Herein, we report all solution-processed green quantum-dot light-emitting diodes
      (G-QLEDs) by introducing a perfluorinated ionomer (PFI, Nafion 117) into quantum
      dots (QDs) to improve hole injection. To reduce the energy level mismatch between
      the hole transporting layer (HTL) and QDs and exciton quenching on the metal
      oxide surface, a PFI-mixed copper-doped nickel oxide (Cu-NiO) HTL was introduced
      for G-QLEDs. Mixing Cu-NiO with a PFI increases the work function and induces
      phase separation between Cu-NiO and PFI; thus, energy band bending occurs on the
      surface such that effective hole injection can be possible. The phase-separated
      PFI molecules on HTL affect the thickness and compactness of G-QDs and make a
      smooth interface between G-QDs and HTL. The G-QLED with a PFI and Cu-NiO mixture
      HTL exhibits the maximum current efficiency (CEmax), power efficiency (PEmax),
      and external quantum efficiency (EQEmax) of 7.3 cd A-1, 2.1 lm W-1, and 2.14%,
      respectively, which are about 4 times those of the QLED with a Cu-NiO HTL.

PMID- 29632919
TI  - Bundle formation of supramolecular fibers of amphiphilic diarylethene by
      depletion force.
AB  - Supramolecular nanofibers composed of the closed-ring isomer of a diarylethene
      formed bundles in a methylcellulose aqueous solution by depletion force while the
      spheres composed of the open-ring isomer were not coagulated. Upon irradiation
      with UV light to the suspension of the open-ring isomer, fibers were found to be
      generated and the formed submillimeter-sized bundles showed a photoinduced
      shrinking of more than 100 MUm under visible light irradiation.

PMID- 29632920
TI  - Metal organic framework-derived CoPS/N-doped carbon for efficient
      electrocatalytic hydrogen evolution.
AB  - Electrocatalytic hydrogen evolution has attracted a great deal of attention due
      to the urgent need for clean energy. Herein, we demonstrate the synthesis of
      ternary pyrite-type cobalt phosphosulphide (CoPS) nanoparticles supported on a
      nitrogen-doped carbon matrix, CoPS/N-C, through carbonization and subsequent
      phosphosulfurization of Co-based zeolitic imidazolate frameworks (ZIF-67), as
      promising hydrogen evolution reaction (HER) electrocatalysts in both acidic and
      alkaline solutions. The polyhedral structure of ZIF-67 can be well maintained in
      the as-prepared CoPS/N-C nanocomposites. In particular, CoPS/N-C provides a
      geometric catalytic current density of -10 mA cm-2 at overpotentials of -80 and 
      148 mV vs. a reversible hydrogen electrode (RHE) and a Tafel slope of 68 and 78
      mV dec-1 in 0.5 M H2SO4 and 1 M KOH, respectively, which is superior to most of
      the transition metal phosphosulfide materials. This MOF-derived synthesis of a
      transition metal phosphosulfide supported heteroatom-doped carbon matrix provides
      a promising opportunity for the development of highly efficient electrocatalysts
      for renewable energy devices.

PMID- 29632921
TI  - Carbon-sulfur bond formation by reductive elimination of gold(iii) thiolates.
AB  - Whereas the reaction of the gold(iii) pincer complex (C^N^C)AuCl with 1-adamantyl
      thiol (AdSH) in the presence of base affords (C^N^C)AuSAd, the same reaction in
      the absence of base leads to formation of aryl thioethers as the products of
      reductive elimination of the Au-C and Au-S ligands (C^N^C = dianion of 2-6
      diphenylpyridine or 2-6-diphenylpyrazine). Although high chemical stability is
      usually taken as a characteristic of pincer complexes, results show that thiols
      are capable of cleaving one of the pincer Au-C bonds. This reaction is not simply
      a function of S-H acidity, since no cleavage takes place with other more acidic X
      H compounds, such as carbazole, amides, phenols and malonates. The reductive C-S
      elimination follows a second-order rate law, -d[1a]/dt = k[1a][AdSH]. Reductive
      elimination is enabled by displacement of the N-donor by thiol; this provides the
      conformational flexibility necessary for C-S bond formation to occur.
      Alternatively, reductive C-S bond formation can be induced by reaction of pre
      formed thiolates (C^N^C)AuSR with a strong Bronsted acid, followed by addition of
      SMe2 as base. On the other hand, treatment of (C^N^C)AuR (R = Me, aryl, alkynyl)
      with thiols under similar conditions leads to selective C-C rather than C-S bond
      formation. The reaction of (C^N^C)AuSAd with H+ in the absence of a donor ligand
      affords the thiolato-bridged complex [{(C^N-CH)Au(MU-SAd)}2]2+ which was
      crystallographically characterised.

PMID- 29632922
TI  - Gold(i)- and rhodium(iii)-catalyzed formal regiodivergent C-H alkynylation of 1
      arylpyrazolones.
AB  - Formal regiodivergent C-H alkynylation of 1-aryl-5-pyrazolones has been realized
      under the catalysis of Rh(iii) and Au(i) complexes by using a hypervalent iodine
      reagent as the alkyne source. Mechanistic studies indicate that the
      regioselectivity is ascribed to not only the choice of the catalyst but also the
      nature of the substrate. The substrate scope and functional group compatibility
      have been fully examined.

PMID- 29632924
TI  - Sodium triethylborohydride as a catalyst for the dehydrogenative silylation of
      terminal alkynes with hydrosilanes.
AB  - The first example of sodium triethylborohydride-catalyzed C(sp)-H bond silylation
      is reported. The reaction of aromatic and aliphatic alkynes with aromatic
      hydrosilanes and hydrosiloxanes proceeded in a highly selective manner to afford
      dehydrocoupling products. Competitive hydrosilylation of the terminal alkyne did
      not occur as a side-reaction. In view of the above it is remarkable that NaHBEt3
      is commonly used as a reducing agent generating active transition-metal catalysts
      in situ in other hydrosilylation reactions.

PMID- 29632923
TI  - Anti-anemia effects of ginsenoside Rk3 and ginsenoside Rh4 on mice with ribavirin
      induced anemia.
AB  - Ginsenoside Rk3 (Rk3) and ginsenoside Rh4 (Rh4) have been reported to have
      therapeutic effects on a variety of diseases including some hematological
      diseases. The aim of the present study was to treat ribavirin-induced anemia in
      mice with Rk3 and Rh4 and explore the therapeutic mechanisms. All the
      experimental mice were randomly divided into 10 groups (the normal group, the
      control group, the model group, the erythropoietin (EPO) group, and 6 groups of
      different doses of Rk3 and Rh4, n = 10 per group). The changes in the hemograms,
      the content of cytokines, the number of hematopoietic cells and viscera damage
      were observed in the experiment. The results showed that the red blood cell
      count, the hemoglobin amount and the hematocrit of mice in the ginsenoside groups
      could be restored to normal values in a short time, and the effects of both Rk3
      and Rh4 are obviously better than those of EPO. Moreover, some positive
      regulators (EPO, erythroid transcription factor-1, and interleukin-3) related to
      hematopoiesis increased and some negative regulators (interferon-gamma and tumour
      necrosis factor-alpha) decreased in vivo after the injection of Rk3 or Rh4. These
      two ginsenosides did little damage to viscera and produced different degrees of
      increase in the hematopoietic cells in the bone marrow and spleen, which
      indicated that Rk3 promoted bone marrow and extramedullary haematopoiesis while
      Rh4 promoted extramedullary hematopoiesis. Therefore, both Rk3 and Rh4 could be
      considered new therapeutic drugs for treating anemia.

PMID- 29632925
TI  - Zr-Based MOFs integrated with a chromophoric ruthenium complex for specific and
      reversible Hg2+ sensing.
AB  - A novel metal-organic framework of RuUiO-67 was successfully fabricated and
      exploited as a chemical sensor for the colorimetric detection of Hg2+. The
      chromophoric Ru complex in RuUiO-67 was designed as a Hg2+ recognition site and a
      signal reporter. The elaborated probe exhibited a rapid colorimetric response,
      high selectivity, and sub-micromolar sensitivity for Hg2+ detection.

PMID- 29632926
TI  - Binding-promoted chemical reaction in the nanospace of a binding site: effects of
      environmental constriction.
AB  - Chemical reactions in a confined nanospace can be very different from those in
      solution. Imine formation between molecular amines and an aldehyde inside a
      molecularly imprinted receptor was promoted strongly by the binding. Although how
      well the amine fit in the binding pocket and its electronic nature both
      influenced the reaction, the freedom of movement for the amine was the most
      important factor determining the binding-normalized reactivity.

PMID- 29632927
TI  - Impact of different sequences of mechanical and thermal processing on the
      rheological properties of Porphyridium cruentum and Chlorella vulgaris as
      functional food ingredients.
AB  - Microalgae are a promising and sustainable source for enhancing the nutritional
      value of food products. Moreover, incorporation of the total biomass might
      contribute to the structural properties of the enriched food product. Our
      previous study demonstrated the potential of Porphyridium cruentum and Chlorella
      vulgaris as multifunctional food ingredients, as they displayed interesting
      rheological properties after applying a specific combination of mechanical and
      thermal processing. The aim of the current study was to investigate the impact of
      a different sequence of high pressure homogenization (HPH) and thermal processing
      on the thickening and gelling potential of these microalgal biomasses in aqueous
      suspensions. Thermal processing largely increased the gel strength and viscosity
      of both microalgae, which was ascribed to larger and stronger aggregates as a
      result of partial solubilization of polymers, while subsequent HPH generally
      reduced the rheological properties. Interestingly, large amounts of intact cells
      were still observed for both microalgae when HPH was performed after a thermal
      treatment, irrespective of the applied homogenization pressure, implying that
      cell disruption was hindered by the preceding thermal treatment. Although thermal
      processing was regarded as the most effective processing technique to obtain
      increased rheological properties, the combination with a preceding HPH treatment
      should still be considered when cell disruption is desired, for instance to
      increase the bioavailability of intracellular components. Finally, biomass of P.
      cruentum showed the largest potential for use as a structuring agent, as the gel
      strength and viscosity in thermally treated suspensions of this microalga were
      about 10 times higher than for C. vulgaris.

PMID- 29632928
TI  - Stereoselective and regioselective 5-exo-dig cyclization of 8-alkynylnaphthalen-1
      amines for the synthesis of (E)-2-(arylthio)alkylene-1,2-dihydrobenzo[cd]indoles.
AB  - A palladium and iodine-cocatalyzed 5-exo-dig aza-thiocyclization of 8
      alkynylnaphthalen-1-amines for the synthesis of (E)-2-alkylene-1,2
      dihydrobenzo[cd]indole thioethers is reported. As a result of broad reaction
      scope, simple operation, mild conditions, and high stereoselectivity and
      regioselectivity, this reaction should have potential utility in organic
      synthesis.

PMID- 29632929
TI  - A coarse grained molecular dynamics simulation study on the structural properties
      of carbon nanotube-dendrimer composites.
AB  - By employing coarse grained (CG) molecular dynamics (MD) simulation, the effect
      of the size and hydrophilic/hydrophobic properties of the interior/exterior
      structures of the dendrimers in carbon nanotube (CNT)-dendrimer composites has
      been studied, to find a stable composite with high solubility in water and the
      capability to be used in drug delivery applications. For this purpose, composites
      consisting of core-shell dendrimer complexes including: [PPI{core}-PAMAM{shell}],
      [PAMAM{core}-polyethyleneglycol (PEG){shell}] and [PAMAM{core}-fattyacid
      (FTA){shell}] were constructed. A new CG model for the fatty acid (FTA) molecules
      as functionalized to the dendrimer was developed, which, unlike the previous
      models, could generate the structural conformations of the FTA properly. The
      obtained results indicated that the dendrimer complexes with short FTA chains can
      form stable composites with the CNT. Also, it was found that the pristine PAMAM
      and PPI-PAMAM with small PPI, and PAMAM-PEG dendrimers with short PEG chains, can
      distribute their chains into the water medium and interact with the CNT
      efficiently, to form a stable water-soluble CNT-dendrimer composite. The results
      demonstrated that the structural difference between the interior and exterior of
      a core-shell dendrimer complex can prevent the core and the interior layers of
      the dendrimer complex from interacting with the CNT. An overall analysis of the
      results manifested that the CNT-PAMAM:4-PEG:4 is the most stable composite, due
      to strong binding of the dendrimer with the CNT while also having high solubility
      in water, and its core retains its structure properly and unchanged, suitable for
      encapsulating drugs in the targeted delivery applications.

PMID- 29632930
TI  - Disordered langasites La3Ga5MO14 : Eu3+ (M = Si, Ge, Ti) as red-emitting LED
      phosphors.
AB  - Polycrystalline powders of La3Ga5SiO14 (LGSi), La3Ga5GeO14 (LGGe), and
      La3Ga5TiO14 (LGTi) doped with Eu3+ were studied with respect to their use as
      luminescent materials in solid state lighting based on light-emitting diodes. The
      langasites were synthesized with up to 35% of trivalent europium to achieve the
      highest possible doping amount. According to diffuse reflection measurements the
      undoped compounds have band gap energies of 4.51 eV (LGSi), 4.54 eV (LGGe) and
      4.07 eV (LGTi). The luminescence behavior between 77 K and 500 K was
      investigated, including excitation, emission and lifetime measurements to analyze
      the impact of the structural differences between the three langasites on the
      spectroscopic properties of the materials. Depending on the excitation
      wavelengths, 300 nm (charge transfer) and 394 nm (4f levels, i.e.7F0 -> 5L6),
      different quenching temperatures were achieved for LGSi : Eu3+ 20% (TQ,300 = 438
      K, TQ,394 = 422 K), LGGe : Eu3+ 20% (TQ,300 = 325 K, TQ,394 = 441 K) and LGTi :
      Eu3+ 20% (TQ,300 = 500 K, TQ,394 = 467 K). The quenching observed can be
      explained by three semi-quantitative configurational coordinate diagrams.
      Independent from the excitation wavelength and the temperature (77-300 K) decay
      times of 1.1 ms were measured. At room temperature and with an excitation
      wavelength of 394 nm maximum quantum efficiencies of 40% for LGSi : Eu, of 80%
      for LGGe : Eu, and of 81% for LGTi : Eu were reached. Finally, to prove the
      applicability as red LED phosphors, the langasites were built into LEDs with
      (In,Ga)N chips emitting at 394 nm.

PMID- 29632931
TI  - Bias-dependent transport properties of passivated tilted black phosphorene
      nanoribbons.
AB  - Using the density functional theory incorporated with a non-equilibrium Green's
      function (NEGF) technique, we explored the bias-dependent transport of tilted
      phosphorene nanoribbons. Herein, we considered three types of nanoribbons: self
      passivated (TPNRself), H-passivated (TPNRH), and O-passivated (TPNRO) systems.
      The TPNRself showed an indirect band gap of 0.53 eV, whereas the TPNRH displayed
      a direct band gap of 1.32 eV. In TPNRO, we observed a spin-polarized band
      structure with a spin-dependent band gap. We found that the bias-dependent I-V
      curve was dependent on the passivation effect. In TPNRself and TPNRH, the current
      monotonically increased with an external bias, but the magnitude of the current
      in TPNRself was more than 10 times than that in TPNRself. Unlike the I-V
      characteristics in TPNRself and TPNRH, the current in TPNRO almost vanished
      beyond an external bias of 1.7 V. Mostly, the bias-dependent I-V was interpreted
      based on the band structure in the lead parts. However, we found that this
      conventional approach was not sufficient to analyze the I-V curve. Indeed, we
      showed that the detailed I-V curve could be understood by calculating the bias
      dependent density of states in the scattering part related to the transmission
      channel. It was also found that the electron flow channel was dependent on the
      passivation effect and uniformly distributed over the entire nanoribbon in
      TPNRself and TPNRH. In contrast, the electron flowed mostly along the edge line
      in TPNRO. Moreover, we have found that spin polarization in the conduction
      current can be manipulated by an external bias, and this may suggest that the
      TPNRO can be utilized for potential spintronic applications.

PMID- 29632932
TI  - A headgroup linker perturbs pKavia acyl chain migration: designing base-labile
      supramolecular assemblies.
AB  - Acyl chain transfer, which perturbs the protonation equilibrium of amine and
      reduces the apparent pKa by 2.0-2.5 units, is used to develop a liposome-based
      drug delivery system.

PMID- 29632933
TI  - Influence of Cassia grandis galactomannan on the properties of sponge cakes: a
      substitute for fat.
AB  - Here we have proposed to evaluate potential replacers of fat in sponge cake
      formulations. Our investigation consisted initially of monitoring the physical
      chemical changes in sponge cake batters caused by gradually replacing the
      vegetable fat/margarine of a control sample (standard sponge cake recipe) with
      galactomannan extracted from the seeds of Cassia grandis. Several samples were
      prepared where a 100% concentration of vegetable fat was substituted with
      galactomannan in different concentrations. We then compared both microscopic and
      macroscopic characteristics of pure fat cake batter formulations and formulations
      with controlled fat/galactomannan mixtures. At this first stage, rheometry and
      optical microscopy were employed to characterize the rheological features and air
      bubble distribution in the batters. In the second stage, the effects of fat
      substitution with galactomannan, now for the final baked cakes, were also
      monitored. Scanning electron microscopy (SEM) and standard sensorial tests were
      performed in order to correlate the final color, texture, and taste
      characteristics of the final sponge cake and those characteristics obtained
      initially for the batter. According to the statistical analysis of the data, a
      75% fat replacement with galactomannan at only 1.0% concentration was achieved,
      while successfully maintaining surface microstructure, sensory acceptance, and
      rheological behavior similar to the original formulation containing only fat.
      Regarding vegetable fat substitution with galactomannan, our results allow us to
      conclude that rheometry and bubble distribution tests on the initial batters are
      useful indicators of the final cake quality.

PMID- 29632934
TI  - Nano-assemblies of cationic mPEG brush block copolymers with gadolinium
      polyoxotungstate [Gd(W5O18)2]9- form stable, high relaxivity MRI contrast agents.
AB  - Polyoxometalates (POMs) incorporating paramagnetic ions, such as gadolinium, show
      promise as contrast agents for application in magnetic resonance imaging (MRI).
      Specifically, [Gd(W5O18)2]9- (denoted as GdWO) has been reported to have a higher
      relaxivity than commercially available contrast agents, but it's clinical utility
      has been limited by the intrinsic instability of POMs at physiological pH (7.4).
      In the current report we present a stability study on neat GdWO and nano
      assemblies of block copolymers with GdWO in the pH range 5.0-7.4 to assess their
      suitability as MRI contrast agents. Neat GdWO only maintained structural
      stability between pH 5.4 and 6.4, and demonstrated poor MRI contrast at pH 7.4.
      To address this pH instability, GdWO was self-assembled with cationic mPEG brush
      block copolymers containing 20 or 40 units derived from the cationic monomer, 2
      dimethylaminoethyl methacrylate (DMAEMA). Nano-assemblies with different charge
      ratios were synthesised and characterised according to their size, stability,
      contrasting properties and toxicity. The longitudinal relaxivity (r1) of the nano
      assemblies was found to be dependent on the charge ratio, but not on the length
      of the cationic polymer block. Further investigation of PDMAEMA20 nano-assemblies
      demonstrated that they were stable over the pH range 5.0-7.4, exhibiting a higher
      r1 than either neat GdWO (2.77 s-1 mM-1) or clinical MRI contrast agent Gd-DTPA
      (4.1 s-1 mM-1) at pH 7.4. Importantly, the nano-assembly with the lowest charge
      ratio (0.2), showed the highest r1 (12.1 s-1 mM-1) whilst, stabilising GdWO over
      the pH range studied, eliciting low toxicity with MDA-MB231 cells.

PMID- 29632935
TI  - The side effects of platinum-based chemotherapy drugs: a review for chemists.
AB  - The platinum-based drugs cisplatin, carboplatin and oxaliplatin are regularly
      prescribed in the treatment of cancer and while they are effective, their use is
      limited by their severe, dose-limiting side effects (also referred to as adverse
      effects/events). In total, a cancer patient can experience any combination of
      around 40 specific side effects. The dose-limiting side effect for cisplatin is
      nephrotoxicity, for carboplatin it is myelosuppression, and for oxaliplatin it is
      neurotoxicity. Other common side effects include anaphylaxis, cytopenias
      (including leukopenia and neutropenia, thrombocytopenia, and anaemia),
      hepatotoxicity, ototoxicity, cardiotoxicity, nausea and vomiting, diarrhea,
      mucositis, stomatitis, pain, alopecia, anorexia, cachexia, and asthenia. The side
      effects may require patients to be prescribed dose reductions in their platinum
      drugs of between 25 and 100%. Furthermore, patients require extensive monitoring
      of their biochemistries, kidney and liver function, and depending on the drug,
      hearing tests. Finally, patients are commonly co-prescribed additional non
      chemotherapy based drugs to treat the side effects which can include antiemetics,
      antibiotics and myeloid growth factors, mannitol, propafenone, saline
      hyperhydration, magnesium supplements, monoclonal antibody cytokine blockers, and
      antioxidants.

PMID- 29632936
TI  - [18F]fluoro-benziodoxole: a no-carrier-added electrophilic fluorinating reagent.
      Rapid, simple radiosynthesis, purification and application for fluorine-18
      labelling.
AB  - Operationally simple radiosynthesis and purification of [18F]fluoro-benziodoxole
      was developed starting from a cyclotron produced [18F]F- precursor, [18F]TBAF,
      and tosyl-benziodoxole. The synthetic utility of [18F]fluoro-benziodoxole was
      demonstrated by electrophilic fluorocyclization of o-styrilamides proceeding with
      high RCC (typically 50-90%) and high molar activity (up to 396 GBq MUmol-1).

PMID- 29632937
TI  - A potential method to improve the in vitro cytotoxicity of half-sandwich Os(ii)
      complexes against A2780 cells.
AB  - The [Os(eta6-pcym)(dpa)(VP)]PF6 (1-VP) complex contains the histone deacetylase
      (HDAC) inhibitor valproate (2-propylpentanoate; VP) as a monodentate O-donor
      ligand and shows ca. 3-fold higher in vitro cytotoxicity against A2780 human
      ovarian carcinoma cells than its chlorido analogue [Os(eta6-pcym)(dpa)Cl]PF6 (1
      Cl); pcym = 1-methyl-4-(propan-2-yl)benzene (p-cymene), dpa = 2,2'
      dipyridylamine. The complex 1-VP showed promising selectivity towards the A2780
      ovarian carcinoma cell line (IC50 = 20.9 MUM) over normal human hepatocytes (IC50
      > 200.0 MUM). Moreover, the complex 1-VP was found to be inactive against MCF-7
      (breast adenocarcinoma), PANC-1 (pancreatic adenocarcinoma) and HT-29 (colon
      carcinoma) up to a concentration of 100 MUM. Detailed flow cytometry studies
      indicated that treatment of A2780 cells with complex 1-VP led to induction of
      apoptosis, production of reactive oxygen species (ROS) and superoxide (SO) anion
      radicals, as well as mitochondrial membrane potential depletion and cell cycle
      perturbations. The microscopic assessment (standard hematoxylin/eosin staining)
      revealed signs of morphological changes associated with the progression of
      apoptosis in A2780 cells treated with the IC50 concentration of the complex 1-VP.
      Consistent with the intracellular production of ROS and SO, the complex 1-VP
      induced hydroxyl radical formation, as proved by EPR spin trapping experiments.
      This case study suggests that replacement of the chlorido ligand of half-sandwich
      Os(ii) complexes by a releasable monodentate biologically active ligand (e.g., VP
      used in this study) is an effective strategy for the development of novel non
      platinum cytotoxic agents.

PMID- 29632938
TI  - Beneficial effects of Cirsium japonicum var. maackii on menopausal symptoms in
      ovariectomized rats.
AB  - In women, menopause refers to a series of physiological and mental symptoms of
      distress that result from a decrease in 17beta-estradiol. In addition to the loss
      of fertility, the symptoms include facial flushing, depression, osteoporosis,
      sexual dysfunction, and genitourinary atrophy. Cirsium japonicum var. maackii is
      a perennial herbaceous species found in the mountains and fields of Korea, China,
      and Japan. The medicinal uses of C. japonicum include antioxidant, antidiabetic,
      antitumor, antifungal, and anti-inflammatory activities. We investigated the
      effect of C. japonicum extract in a rat model of menopause that exhibited rapid
      estrogen decline induced by ovariectomy (OVX rats). The rats were treated with C.
      japonicum extract for 10 weeks and the following parameters were measured: food
      intake, feed efficiency, body weight, total cholesterol, triglyceride, LDL
      cholesterol, HDL-cholesterol, liver weight, 17beta-estradiol, uterus weight, AST,
      ALT, bone mineral density (BMD), bone alkaline phosphatase, calcitonin, and
      osteocalcin. In OVX rats, the administration of 50 and 100 mg kg-1C. japonicum
      extract significantly decreased body weight, total cholesterol, triglyceride, HDL
      cholesterol, and LDL-cholesterol and significantly increased 17beta-estradiol and
      BMD. During the light/dark box test, the C. japonicum treatment group (100 mg kg
      1) spent more time in the light chamber than in the dark area, which was
      reflective of their diurnal nature. Using a molecular docking simulation, we
      predicted the plausible binding mode of the active compounds of C. japonicum with
      the ligand binding domain of estrogen receptor (ER)-alpha and ER-beta. These
      results showed that C. japonicum extract can treat the symptoms before and after
      the menopause.

PMID- 29632939
TI  - Confined metal Ge quantum dots in carbon nanofibers for stable rechargeable
      batteries.
AB  - As a promising alloy-type anode material for rechargeable batteries, the metal
      germanium (Ge) shows high capacity, but it suffers from a fast capacity fading
      problem caused by a large volume expansion during lithiation/delithiation cycles.
      In this study, via a facile electrospinning method, we optimized the combination
      structure of Ge quantum dots (QDs) and carbon nanofibers (CNFs). Specifically, Ge
      QDs with a diameter of 4-7 nm were highly dispersed in porous (pore size 10-150
      nm) CNFs. The hybridized Ge/CNF nanocomposite exhibited remarkable Li storage
      performances such as high reversible capacity (1204 mA h g-1 at a current density
      of 200 mA g-1), high capacity retention (87.1% after 100 cycles) and excellent
      rate property (760 mA h g-1 at 3000 mA g-1). The improved electrochemical
      performance was due to the synergistic effects of Ge QDs and carbon nanofibers;
      this effectively alleviated the volume expansion problem, prevented the
      agglomeration of Ge, maintained the structural stability of the nanocomposite,
      and improved the electrode kinetics of diffusion of Li ions.

PMID- 29632940
TI  - Anti-Abeta drug candidates in clinical trials and plasmonic nanoparticle-based
      drug-screen for Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most common cause of neurodegenerative disorder
      in elderly people, and has become a social problem in aging societies globally.
      Amyloid-beta (Abeta) aggregates (i.e., Abeta fibrils and plaques) present in the
      brains of AD patients are hallmarks of AD. Although various promising anti-Abeta
      drugs have been tested in pre-clinical and randomized controlled trials, the
      trial results have not yet been translated into clinical practice due to
      increasing time and cost of drug development. Recent investigations have
      addressed how the formation of Abeta aggregates is influenced by the surface of
      gold nanoparticles (AuNPs) to obtain a detailed understanding of the in vivo
      process of amyloid formation. Particularly, AuNPs catalytically provide
      nucleation sites to accelerate the formation of Abeta aggregates. Moreover, AuNPs
      have great potential as a sensing tool due to their optical property. Employing
      this dual function (i.e., catalytic and optical property), AuNP-based colorimetry
      is highlighted as a simple and innovative method for monitoring the efficacy of
      anti-Abeta reagents. In this review, we briefly survey important developments and
      designs of anti-Abeta drugs. The significance and perspectives of AuNP-based drug
      screening in pharmacologic research are also discussed.

PMID- 29632941
TI  - Activating [4 + 4] photoreactivity in the solid-state via complexation: from 9
      (methylaminomethyl)anthracene to its silver(i) complexes.
AB  - The [4 + 4] photoreactivity of the anthracene derivative 9
      (methylaminomethyl)anthracene (MAMA) has been investigated in solution, gel
      medium and in the solid state. While quantitative formation of the cyloaddition
      photoproduct was achieved upon irradiation at lambda = 365 nm of ethanol
      solutions of MAMA, only partial and slow conversion was detected in gels of low
      molecular weight gelators, and solid-state reactivity was not observed due to the
      unfavourable relative orientation of the anthracene moieties in the crystal. In
      hexafluorophosphate, tetrafluoroborate and nitrate silver(i) complexes, however,
      9-(methylaminomethyl)anthracene exhibits a more favourable mutual orientation for
      the aromatic fragments, and [4 + 4] photoreactivity resulted. All compounds were
      structurally characterized via single crystal and/or X-ray powder diffraction and
      by Raman spectroscopy; this last technique proved effective in detection of the
      photoproduct in all solid state complexes.

PMID- 29632942
TI  - Effect of divalent versus monovalent cations on the MS2 retention capacity of
      amino-functionalized ceramic filters.
AB  - Ceramic capillary membranes conditioned for virus filtration via
      functionalization with n-(3-trimethoxysilylpropyl)diethylenetriamine (TPDA) are
      analyzed with respect to their virus retention capacity when using feed solutions
      based on monovalent and divalent salts (NaCl, MgCl2). The log reduction value
      (LRV) by operating in dead-end mode using the model bacteriophage MS2 with a
      diameter of 25 nm and an IEP of 3.9 is as high as 9.6 when using feeds containing
      MgCl2. In contrast, a lesser LRV of 6.4 is observed for feed solutions based on
      NaCl. The TPDA functionalized surface is simulated at the atomistic scale using
      explicit-solvent molecular dynamics in the presence of either Na+ or Mg2+ ions.
      Computational prediction of the binding free energy reveals that the Mg2+ ions
      remain preferentially adsorbed at the surface, whereas Na+ ions form a weakly
      bound dissolved ionic layer. The charge shielding between surface and amino
      groups by the adsorbed Mg2+ ions leads to an upright orientation of the TPDA
      molecules as opposed to a more tilted orientation in the presence of Na+ ions.
      The resulting better accessibility of the TPDA molecules is very likely
      responsible for the enhanced virus retention capacity using a feed solution with
      Mg2+ ions.

PMID- 29632943
TI  - Nail dryer devices: a measured spectral irradiance and labelling review.
AB  - The popularity of nail beauty has increased during the last few years in Spain,
      as well as in other countries. Nowadays there are a large number of nail dryer
      devices in the market with ultraviolet (UV) fluorescent lamps, light emitting
      diodes (LED) or a combination of both. The different spectral emissions of each
      individual nail dryer device require particular nail polishes, which are
      polymerized by specific wavelengths and a controlled exposure time to achieve the
      desired results. We have measured and analyzed the emission of 28 nail dryer
      devices currently in use in Spanish beauty centers. The emission of each
      individual nail dryer device showed a particular spectral distribution and
      maximum intensity, especially those with fluorescent lamps or LED/UV
      combinations. About 30% of the devices emitted more UV-A radiation than that
      received in Barcelona at solar noon in summer. Nevertheless, in all cases the
      erythemal irradiance was low, similarly to ambient values at solar noon in winter
      or when the solar altitude is low. The erythemal doses corresponding to a typical
      session were, therefore, lower than those received from sunlight at summer midday
      at equivalent exposure times. The biological irradiances for photoaging (skin
      sagging and elastosis) showed high variability depending on the device,
      especially for fluorescent lamps. Since the emission of LED-based devices is
      centered in the visible region, erythemal and photoaging irradiances were low. An
      analysis of the labelling showed that 85% of the devices had a visible label,
      although 23% contained some errors, according to the EN 60335-1 guideline.

PMID- 29632944
TI  - Dietary supplementation with omega-3 polyunsaturated fatty acid-rich oils
      protects against visible-light-induced retinal damage in vivo.
AB  - The effects of administering omega-3 (omega-3) polyunsaturated fatty acid (PUFA)
      rich oils on visible-light-induced retinal damage were investigated in rabbits.
      The mole percentages of alpha-linolenic acid in sea buckthorn berry oil, sea
      buckthorn oil (SO), sea buckthorn seed oil and flaxseed oil (FO) were 2.12%,
      12.98%, 31.56% and 55.41%, respectively. Algal oil (AO) contains 33.34%
      docosahexaenoic acid. SO has the highest total phenolic content (63.42 +/- 0.59
      mg SAE per 100 g) amongst these oils. The administration of SO, FO and AO
      provided structural and functional protection to the retina. In the retina, we
      observed a significant increase in the levels of DHA in the AO group compared
      with the normal group. The mechanism of retinal protection by SO, FO and AO
      involves up-regulating the expression of nuclear factor erythroid-2 related
      factor 2 and haem oxygenase-1. The levels of interleukin-1 beta, tumour necrosis
      factor-alpha, interleukin-8, and cyclooxygenase 2 in the retina were
      significantly reduced with AO treatment. The administration of AO resulted in the
      down-regulation of nuclear factor kappa B mRNA expression. In addition, the
      treatment with AO significantly attenuated the light-induced apoptosis and
      angiogenesis in the retina. These results suggest that dietary omega-3 PUFA-rich
      oils protect against visible-light-induced retinal damage.

PMID- 29632945
TI  - Nonconductive layered hexagonal boron nitride exfoliation by bipolar
      electrochemistry.
AB  - Boron nitride (h-BN), which is an isoelectronic analogue of graphite, has
      received immense attention due to its unique physical and chemical properties.
      Numerous methods have been developed to isolate few-layered h-BN nanosheets.
      These include chemical vapour deposition, solution-based exfoliation and ball
      milling amongst others. The bipolar electrochemical method is one of the popular,
      scalable and water based exfoliation methods which has been applied to graphite,
      layered transition metal dichalcogenides and black phosphorus. This method was
      not applied to insulators as this has been assumed to be an impossible task. In
      this study, we report a solution-based, scalable and time efficient bipolar
      electrochemical method for the direct exfoliation of bulk insulator, layered h-BN
      into few-layered h-BN nanosheets based on bipolar electrochemistry. The
      electrochemical exfoliation of nonconductive materials, h-BN, opens the way to
      the application of this scalable method to the whole spectrum of non-conductive
      layered materials. This facile method offers an alternative platform for h-BN
      electrochemical exfoliation in wide-ranging fields encompassing electronics and
      biomedical science.

PMID- 29632946
TI  - Critical strain for Sn incorporation into spontaneously graded Ge/GeSn core/shell
      nanowires.
AB  - We address the role of non-uniform composition, as measured by energy-dispersive
      x-ray spectroscopy, in the elastic properties of core/shell nanowires for the
      Ge/GeSn system. In particular, by finite element method simulations and
      transmission electron diffraction measurements, we estimate the residual misfit
      strain when a radial gradient in Sn and a Ge segregation at the nanowire facet
      edges are present. An elastic stiffening of the structure with respect to the
      uniform one is concluded, particularly for the axial strain component. More
      importantly, refined predictions linking the strain and the Sn percentage at the
      nanowire facets enable us to quantitatively determine the maximum compressive
      strain value allowing for additional Sn incorporation into a GeSn alloy. The
      progressive incorporation with increasing shell thickness, under constant growth
      conditions, is specifically induced by the nanowire configuration, where a larger
      elastic relaxation of the misfit strain takes place.

PMID- 29632947
TI  - Relevance of ion clusters for Li transport at elevated salt concentrations in
      [Pyr12O1][FTFSI] ionic liquid-based electrolytes.
AB  - In binary ionic liquid/Li salt mixtures with the novel asymmetric anion FTFSI,
      electrophoretic mobility MUi values of all ion species were determined using
      electrophoretic NMR. Li was determined to migrate in negatively charged Li-anion
      clusters towards the anode. This vehicular transport mechanism was shown to have
      decreasing relevance at elevated salt concentrations.

PMID- 29632948
TI  - Gold(i)-catalyzed cross-coupling reactions of aryldiazonium salts with
      organostannanes.
AB  - Gold(i)-catalyzed cross-coupling reactions of aryldiazonium salts with
      organostannanes are described. This redox neutral strategy offers an efficient
      approach to diverse biaryls, vinyl arenes and arylacetylenes. Monitoring the
      reaction with NMR and ESI-MS provided strong evidence for the in situ formation
      of Ph3PAuIR (R = aryl, vinyl and alkynyl) species which is crucial for the
      activation of aryldiazonium salts.

PMID- 29632949
TI  - Designed Learning: Missing Data in Clinical Research.

PMID- 29632950
TI  - We Should Measure What Matters in Bundled Payment Programs.

PMID- 29632951
TI  - Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia Syndrome Treated
      With Sirolimus.

PMID- 29632952
TI  - The Effect of Telehealth on Spending: Thinking Through the Numbers.

PMID- 29632953
TI  - U.S. Food and Drug Administration Precertification Pilot Program for Digital
      Health Software: Weighing the Benefits and Risks.
AB  - In 2017, the U.S. Food and Drug Administration (FDA) announced a new program for
      software classified as a medical device. The Digital Health Software
      Precertification (Pre-Cert) Program is designed to expedite regulatory review for
      companies that demonstrate quality and organizational excellence in software
      development. Although Pre-Cert is intended to promote the worthy goals of access
      and innovation in digital health, many questions have been raised. In particular,
      Pre-Cert may reduce incentives for developers to study the safety and
      effectiveness of their software products before patients start to rely on them.
      Although postmarket surveillance can mitigate risks of these products, the FDA
      does not have as much authority after a product's widespread use to enforce data
      collection deadlines. Pre-Cert may also create confusion for patients and
      physicians, who may believe that marketed products were subject to rigorous
      study.

PMID- 29632954
TI  - Achieving 100% compliance to perioperative antibiotic administration: a quality
      improvement initiative.
AB  - INTRODUCTION: Timely administration of prophylactic antibiotic within 60 minutes
      before surgical incision is important for reducing surgical site infections. This
      quality-improvement initiative aimed to work toward achieving 100% compliance to
      perioperative antibiotic administration. METHODS: We examined the workflow in our
      Anaesthesia Information Management System (AIMS) and proposed interventions using
      cause-and-effect analysis on anonymised anaesthetic records of eligible surgical
      cases extracted from it. This ultimately led to the implementation of an
      antibiotic pop-up reminder. The overall process was done in a few small plan-do
      study-act cycles. These involved raising awareness, education and reorganisation
      of AIMS before actual implementation of the antibiotic pop-up reminder. There was
      ongoing data analysis from August 2014 to September 2016. Compliance was defined
      as documented antibiotic administration within 60 minutes before surgical
      incision or documented reason for omission. RESULTS: Median monthly compliance
      rate, for 33,038 cases before and 28,315 cases after the reminder was
      implemented, increased from 67.0% at baseline to 94.5%. This increase was
      consistent and sustained for a year despite frequent personnel turnover.
      Documentation of antibiotic administration also improved from 81.7% to 99.3%.
      This allowed us to identify and address novel problems that were not apparent
      initially, resulting in several department recommendations. These included
      administering antibiotics later for cases with foreseeably longer-than-expected
      preparation times, and bringing forward antibiotic administration in lower
      segment Caesarean sections. CONCLUSION: The use of information technology and
      implementation of antibiotic pop-up reminder on AIMS streamlined our work
      processes and brought us closer to achieving 100% on-time compliance with
      perioperative antibiotic administration.

PMID- 29632955
TI  - In-stent restenosis assessed by frequency-domain optical coherence tomography
      shows smooth coronary arterial healing process in second-generation drug-eluting
      stents.
AB  - INTRODUCTION: The pathophysiology and mechanism of in-stent restenosis (ISR)
      after implantation of second-generation drug-eluting stents (DESs) are not fully
      clear. We compared the morphological characteristics of ISR between first- and
      second-generation DESs using frequency-domain optical coherence tomography (OCT).
      METHODS: Patients who underwent follow-up coronary angiography (CAG) after first-
      (Cypher and Taxus) and second- (Nobori, Promus Element, Resolute Integrity and
      Xience) generation DES implantations were examined. ISR was defined as lesions of
      over 50% diameter stenosis at follow-up CAG. Frequency-domain OCT was performed
      at the time of revascularisation of ISR. Tissue morphology was assessed at
      minimum lumen area. OCT images of DESs at both early (<= 1 year) and late (> 1
      year) follow-ups were compared. RESULTS: On qualitative OCT assessment, ratios of
      homogeneous, layered, heterogeneous without attenuation and heterogeneous with
      attenuation morphologies were 57.1% 17.1%, 20.0% and 5.7%, respectively, for
      second-generation DES ISR (n = 35), and 16.7%, 25.0%, 25.0% and 33.3%,
      respectively, for first-generation DES ISR (n = 36). At late follow-up,
      homogeneous morphology was significantly higher for second-generation DES ISR
      (second-generation DES ISR: 50.0% vs. first-generation DES ISR: 8.0%; p < 0.01)
      while heterogeneous with attenuation morphology was significantly higher for
      first-generation DES ISR (second-generation DES ISR: 5.6% vs. first-generation
      DES ISR: 44.0%; p < 0.01). CONCLUSION: Homogeneous tissue morphology was more
      frequently found for second-generation DES ISR than first-generation DES ISR,
      especially in the late phase. This finding suggested that neointimal hyperplasia
      was the main mechanism in second-generation DES ISR and the neointima was
      stabilised much like after bare metal stent implantation.

PMID- 29632957
TI  - Making theory from knowledge syntheses useful for public health.

PMID- 29632958
TI  - [Edge filters : Medical indications and clinical application].
AB  - Edge filters are used in aphakic eyes as a substitute of the natural cut-off
      filter of the intact eye or in other causes of a lack of light absorption in the
      eye itself. Furthermore, they can remedy light adaptation disturbances,
      especially in hereditary retinal diseases and retinal dystrophy. They enhance
      contrast and reduce glare. In order to choose an adequate cut-off filter it is
      necessary to let the participants test various filters before prescription.
      Because of the (absolute) absorption of blue light, cut-off filters normally lead
      to a loss of ability to drive.

PMID- 29632956
TI  - Expression analysis of toll-like receptors of Dengue-infected cornea by real-time
      polymerase chain reaction.
AB  - BACKGROUND: Toll-like receptors (TLRs) play a significant role based on innate
      immune mechanism during viral infection. TLR signaling mechanism designates to
      protect the cells from invading viruses. The expression of TLRs during dengue
      virus (DENV) infection not yet well explained. This study evaluates the TLR gene
      expression from DENV-infected patient's cornea. METHODS: Reverse transcriptase
      PCR was performed for the detection and genotyping of viral nucleic acid from
      corneal grafts and DENV-infected cell suspension. TLR expression studies were
      done on DENV-infected cornea by real-time RT2 Profiler PCR Array. RESULTS: The
      reverse transcriptase PCR and genotyping confirmed the presence of DENV-3. TLR
      expression studies revealed the upregulated expression of TLR4, TLR7, TLR9 and
      TLR10. CONCLUSION: Molecular testing of DENV reveals that serological positivity
      induces transmission of the virus through cornea and stimulates the expression of
      TLR4, TLR7, TLR9 and TLR10, which may lead to up-regulation of innate pro
      inflammatory response in the cornea.

PMID- 29632959
TI  - Impact of Fetal Somatic Growth on Pulmonary Valve Annulus Z-Scores During
      Gestation and Through Birth in Patients with Tetralogy of Fallot.
AB  - Previous studies have suggested reduced pulmonary valve annulus (PVA) growth and
      progression of pulmonary outflow obstruction in fetuses with tetralogy of Fallot
      (TOF). The goals of this study were to (1) investigate the trajectory of PVA
      growth in utero, and (2) compare two methods of z-score determination for fetal
      and postnatal PVA size by echocardiography in order to improve prenatal
      counseling for patients with TOF. Fetal echocardiograms (FE) at a single
      institution with a diagnosis of TOF between 8/2008 and 12/2015 were
      retrospectively reviewed. Patients included had at least 2 FEs and 1 immediate
      postnatal echocardiogram (TTE). Fetal and postnatal demographic, clinical, and
      echocardiographic data were collected. Fetal body surface area (BSA) was
      calculated by estimating fetal weight and height; z-scores were determined based
      on fetal gestational age (GA) and BSA for both FEs and TTEs. Fetal PVA z-scores
      by GA or BSA were then compared to postnatal PVA z-scores by BSA. Twenty-two
      patients with 44 FEs and 22 TTEs were included. GA at the first FE was 23 weeks
      +/- 3.4 and 32 weeks +/- 3.1 at the second FE. There was no difference in PVA z
      scores (by BSA) between the first and second FE (p = 0.34), but a decrease in PVA
      z-scores (by BSA) between the second FE and TTE (- 1.6 +/- 0.5 vs. - 2.0 +/- 0.7;
      p = 0.01). Repeat comparison with fetal PVA z-scores indexed to GA revealed no
      difference in z-scores between the first and second FE, but an increase in PVA z
      scores between the second FE (by GA) and TTE (by BSA) (- 4.1 +/- 1.0 vs. - 2.0 +/
      0.7; p < 0.0001). The rate of PVA growth between the two FEs (23 um/day +/- 9.8)
      and between the second FE and TTE (28 um/day +/- 42) remained comparable (p =
      0.57); however, the rate of BSA increase was greater in later gestation (9
      cm2/day +/- 3 vs. 20 cm2/day +/- 11; p = 0.001). In patients with TOF, the rate
      of PVA growth appears to remain consistent through gestation; however, somatic
      growth rate increases in late gestation. Fetal PVA z-scores indexed to GA are
      thus inaccurate in predicting postnatal PVA z-scores typically indexed to BSA.
      This observation should be considered during prenatal consultation and delivery
      planning.

PMID- 29632960
TI  - Prognostic Value of Serum Apelin Level in Children with Heart Failure Secondary
      to Congenital Heart Disease.
AB  - Apelin is an endogenous inotrope that decreased in heart failure (HF). We aimed
      to evaluate the prognostic value of its level in children with HF due to
      congenital heart disease (CHD). Sixty children with HF due to CHD were included
      as a patient group. Sixty healthy children matched for age, sex, and weight
      served as a control group. Chest X-ray, electrocardiogram (ECG),
      echocardiography, and laboratory investigations such as complete blood count, c
      reactive protein, and serum apelin levels were performed for all included
      children at admission. All children were followed up for 3 months. Serum apelin
      level was significantly decreased in patients with HF at admission than healthy
      control group and this decrease went with advanced stage of HF. Serum apelin
      levels were significantly decreased in patients with unfavorable prognosis than
      those with favorable prognosis. At a cutoff lower than 126 ng/l, the sensitivity
      of serum apelin to predict unfavorable prognosis in children with HF was 96% with
      a specificity of 82%. Serum apelin level had a significant positive correlation
      with left ventricular systolic function (P < 0.05). Moreover, it had a
      significant negative correlation with heart rate, respiratory rate, Ross
      classification, c-reactive protein, cardiothoracic ratio, and both left and right
      ventricular dimensions (P < 0.05). Serum apelin level has a good predictive value
      for adverse outcome in children with HF due to CHD.

PMID- 29632961
TI  - Introduction of the second-generation direct-acting antivirals (DAAs) in chronic
      hepatitis C: a register-based study in Sweden.
AB  - PURPOSE: Introduction of the direct-acting antivirals (DAAs) for treatment of
      chronic hepatitis C (CHC) infection has been challenging in all health systems.
      In Sweden, a national protocol for managed introduction was developed. It was
      optional, but all county councils agreed to implement and follow it. The purpose
      of this study was to study (a) cure rates among all patients initiated on
      treatment in 2014-2015, (b) prescribers' adherence to the drug recommendations
      and treatment eligibility criteria in the protocol, and (c) introduction rate in
      the six Swedish healthcare regions. METHOD: A cross-sectional study where
      national data from the Prescribed Drug Register and the quality register InfCare
      Hepatitis defined the study population, and clinical data from the Patient
      Register and InfCare Hepatitis were used to monitor outcomes. Descriptive
      statistics were used. RESULTS: A total of 3447 patients were initiated on
      treatment during 2014-2015. The overall cure rate, based on data from 85% of the
      cohort, was 96%, with variation between genotypes. Adherence to drug
      recommendations increased over time and varied between 43.2 and 94.2%. Adherence
      to the treatment eligibility criteria was initially 80% and increased to 87% when
      treatment restrictions were widened. The introduction rate differed initially
      between the regions and reached stable levels 15-18 months after the launch of
      the first DAA. CONCLUSION: The estimated overall cure rate was 96%, with some
      variations between genotypes. A high level of adherence to the introduction
      protocol as well as similar introduction rates in the health care regions
      indicate that the introduction protocol, alongside with other measures taken,
      contributed considerably to a rapid uptake and equal distribution of DAAs in
      Sweden.

PMID- 29632962
TI  - Policies and availability of orphan medicines in outpatient care in 24 European
      countries.
AB  - PURPOSE: To assess pricing and reimbursement policies specific to orphan
      medicines and the availability and distribution settings of ten recently
      authorised medicinal products suitable for outpatient care with orphan status and
      centralised marketing authorisation in Europe, and whether patients receive these
      products free of charge or have to pay some or all of the costs themselves.
      METHODS: Web survey to authorities and representatives of third party payers in
      the Pharmaceutical Pricing and Reimbursement Information (PPRI) network in April
      2016. RESULTS: In most of the 24 countries, special policies were not implemented
      in the assessment of reimbursement status (22 countries) or in the pricing (20
      countries) of orphan medicines. An average of five of the ten recently authorised
      products per country were available for outpatient care. Products were dispensed
      from community pharmacies in eight countries and from health care units in five
      countries. In four countries, both distribution settings were used. When products
      were dispensed from community pharmacies, patients typically paid some of the
      price themselves. Products dispensed from health care units were often free of
      charge for patients. CONCLUSIONS: Most European countries had not implemented
      pricing and reimbursement policies specific to orphan medicines. The availability
      of orphan products varied between countries. It is important to discuss whether
      orphan medicines should be considered as a separate group in the reimbursement
      regulations in order to secure patient access to these medicines.

PMID- 29632963
TI  - Pacinian corpuscles: an explanation for subcutaneous palmar nodules routinely
      encountered on MR examinations.
AB  - Pacinian corpuscles, the main touch receptors to pressure and vibration, are
      ubiquitous in the deep dermis and hypodermis of the fingers and palms.
      Nevertheless, their existence is largely unknown to most radiologists. We
      frequently noted hyperintense nodules in the palms of patients on water-sensitive
      MRI sequences, but were unable to explain their etiology. We recently encountered
      two patients who had Pacinian corpuscles identified at surgical exploration and
      pathological analysis. Pre-operative MRI examinations in these patients showed T2
      hyperintense subcutaneous palmar nodules corresponding to these corpuscles in a
      pattern identical to those seen incidentally in other patients. Descriptions from
      the dermatopathological and orthopedic literature closely correspond to our MRI
      observations. Based on these data, we hypothesize that the MRI finding that we
      previously noted represents normal Pacinian corpuscles.

PMID- 29632964
TI  - Symptom development in originally asymptomatic CPAM diagnosed prenatally: a
      systematic review.
AB  - PURPOSE: For the approximately three quarters of patients with a prenatal
      diagnosis of congenital pulmonary airway malformation (CPAM) who are asymptomatic
      at birth, the chance of eventually developing symptoms is unknown. We sought to
      explore the natural history of asymptomatic CPAM. METHODS: We searched EMBASE,
      MEDLINE, and the first 50 results from Google Scholar. Studies describing the
      natural history of prenatally diagnosed, initially asymptomatic CPAM were
      included. For asymptomatic patients initially managed non-surgically, we
      tabulated the proportion who went on to develop symptoms as well as the median
      age at symptom development. RESULTS: We included data from 19 retrospective
      studies on 353 patients. Of the 128 patients managed expectantly, 31 (24.2%)
      developed symptoms requiring surgical intervention. The median age at symptom
      development was 7.5 months (range 15 days-5 years). CONCLUSION: The risk for
      developing respiratory symptoms exists with originally asymptomatic CPAM
      patients, but the exact risk is difficult to predict. Parents may be given the
      value of approximately 1 in 4 as an estimate of the proportion of asymptomatic
      CPAM patients who go on to develop symptoms, which will help them make an
      informed decision regarding the option of elective surgery.

PMID- 29632965
TI  - A morphometric analysis of the suitability of the transverse cervical artery as a
      recipient artery in head and neck free flap microvascular reconstruction.
AB  - PURPOSE: Gold standard recipient arteries in head and neck free flap
      microvascular reconstruction are currently branches of the external carotid.
      However, these arteries can be compromised by neck dissection or radiotherapy,
      resulting in 'vessel-depleted neck' and 'frozen neck' respectively. In such
      cases, the transverse cervical artery (TCA) may be a suitable recipient artery.
      METHODS: The origin, course and diameter of the TCA were determined in 46 sides
      of neck from 23 cadavers. The distances from the origin of the TCA to the angle
      of the mandible, floor of the mouth and mandibular symphysis were measured to
      determine the pedicle length required for free flap anastomosis. RESULTS: The TCA
      was present bilaterally in all subjects investigated and its course across the
      posterior triangle of the neck was constant between individuals. The mean
      distances from the origin of the TCA to the angle of mandible, floor of mouth and
      mandibular symphysis were 10.0, 9.2 and 12.6 cm, respectively. There were no
      significant differences in these distances between the left and right sides of
      the neck (p > 0.05 for all comparisons). The distances from the TCA origin to the
      angle of the mandible and floor of the mouth were significantly longer in males
      than in females (p = 0.004) and correlated directly with the greater height of
      males compared to females (p = 0.0004). The mean diameter of the TCA measured 2
      cm from its origin was 2.2 mm. CONCLUSION: The TCA is a suitable and reliable
      recipient artery for free flap microvascular reconstruction, when branches of the
      external carotid artery are unavailable.

PMID- 29632967
TI  - [Fluid resuscitation in adults : Balanced crystalloids vs. saline].

PMID- 29632966
TI  - The functional analysis of SlNCED1 in tomato pollen development.
AB  - Abscisic acid (ABA) regulates plant growth and development, but the role of ABA
      in the development of reproductive organs in tomato has rarely been addressed. In
      the present study, the role of ABA in the regulation of male and female
      gametogenesis as well as pollen development and germination is tested in tomato.
      qRT-PCR and in situ hybridization analysis of 9-cis-epoxycarotenoid dioxygenase
      (SlNCED1), a key enzyme in the ABA biosynthetic pathway, showed high expression
      of SlNCED1 primarily in the meristem during gametogenesis and mainly in ovule,
      stigma, anther/pollen and vascular tissues during floral organ development.
      SlNCED1 expression and ABA accumulation in anther peak at stages 13-14,
      suggesting that ABA plays a role in the primary formation of pollen grains. Over
      expression and suppression of SlNCED1 led to the abnormal development of
      anther/pollen, especially in SlNCED1-OE lines, which have serious pollen
      deterioration. The percentage of pollen germination in wild type is 91.47%,
      whereas it is 6.85% in OE transgenic lines and 38.4% at anthesis in RNAi lines.
      RNA-Seq of anthers shows that SlNCED1-OE can significantly enhance the expression
      of SlPP2Cs and down-regulate the expression of SlMYB108 and SlMYB21, which are
      anther/flower-specific transcriptional factors in tomato. Finally, anther
      transcriptome data indicate that SlNCED1 is involved in ABA-mediated regulation
      in pollen/anther metabolism, cell wall modification, and transcription levels.
      These results support an important role for ABA in the development of
      reproductive organs in tomato and contribute to the elucidation of the underlying
      regulatory mechanisms.

PMID- 29632969
TI  - Emergency ultrasound and echocardiography in patients with infarct-related
      cardiogenic shock : A survey among members of the German Society of Medical
      Intensive Care and Emergency Medicine.
AB  - Current international and national guidelines promote the use of emergency
      echocardiography in patients with cardiogenic shock. We assessed whether these
      recommendations are followed in clinical practice of infarct-related cardiogenic
      shock patients. For this purpose we conducted a web-based survey among all
      members of the German Society of Medical Intensive Care and Emergency Medicine
      (DGIIN); 40% of the DGIIN members completed the survey. Participants reported
      that in their department emergency echocardiography/ultrasound is performed on
      most patients in infarct-related cardiogenic shock presenting to the emergency
      department/chest pain unit or intensive care unit (58.6% versus 81.4%). Only 33%
      stated that on patients admitted directly to the catheterization laboratory
      emergency ultrasound/echocardiography is applied in their institution. Local
      availability of a standardized algorithm was lacking in the majority of
      departments (77.2%). A great proportion (38.3%) of participants stated that they
      personally had no formal training in emergency ultrasound. In order to meet the
      demands of the current guidelines, in addition to integration of ultrasound
      examinations into diagnostic algorithms, a structured training of all emergency
      and intensive care physicians is necessary.

PMID- 29632968
TI  - [Organ assist devices in the future : Limits and perspectives].
AB  - In the last decade, extracorporeal organ assist devices (extracorporeal membrane
      oxygenation [ECMO]) have been increasingly applied to treat the most severe forms
      of respiratory failure and cardiogenic shock, although the underlying scientific
      evidence is still limited and the methods carry a high risk of complications
      despite all technical improvements. The selection of those patients who most
      benefit from these devices is still a great challenge for intensivists and all
      other involved disciplines. Besides the severity of the acute organ failure, it
      is important to thoroughly evaluate etiology and treatment options of the
      underlying disease, comorbidities, and the functional status of the patients in
      an interdisciplinary team. This also includes ethical challenges. Because of the
      complexity of the treatment and the high organizational demands it is reasonable
      to concentrate ECMO treatments in specifically qualified centers and to promote a
      comprehensive scientific analysis of the treatment data.

PMID- 29632970
TI  - [Are the initial pH and the lactate values after cardiopulmonary resuscitation
      always crucial?]
AB  - A 52-year-old man suffered an out-of-hospital cardiac arrest (OHCA) and bystander
      reanimation was immediately started. The initial electrocardiogram indicated
      ventricular fibrillation. After repetitive defibrillations as well as intravenous
      administration of amiodarone, a temporary return of spontaneous circulation
      (ROSC) could be established. Due to unstable cardiovascular conditions with
      recurrence of ventricular fibrillation, mechanical resuscitation with the help of
      the LUCASTM device was initiated, and the patient was admitted to our hospital
      for emergency coronary angiography after a cumulative period of approximately 90
      min. The initial blood gas analysis displayed a significant lactate acidosis with
      a pH value of 6.7. Therefore, in a multidisciplinary team, the decision was made
      against an extracorporeal membrane oxygenation and for a coronary angiography
      under continuation of mechanical resuscitation. After multiple stenting of the
      right coronary artery and left anterior descending coronary artery, permanent
      ROSC could be established. The patient was admitted to our intensive care unit,
      where he was further treated according to the S3-guideline for infarct-related
      cardiogenic shock. In the course of time, the patient was quickly extubated
      without any neurological deficits.

PMID- 29632971
TI  - Simultaneous determination of sulfur compounds from the sulfur pathway in rat
      plasma by liquid chromatography tandem mass spectrometry: application to the
      study of the effect of Shao Fu Zhu Yu decoction.
AB  - A sensitive, accurate, and time-saving approach was developed for the
      simultaneous quantification of eight sulfur compounds in the sulfur pathway,
      which could reflect the status of an organism, including oxidative stress, signal
      transduction, enzyme reaction, and so on. In order to overcome the instability of
      highly reactive sulfhydryl compounds, N-ethylmaleimide derivatization was adopted
      to effectively protect sulfhydryl-containing samples. Using isotope-labeled
      glutathione (GSH-13C2, 15N), the validated method was demonstrated to offer
      satisfactory linearity, accuracy, and precision. Separation was done by UHPLC,
      using a BEH amide column. Accordingly, 0.1% formic acid acetonitrile was selected
      as the precipitant. A tandem mass spectrometer was coupled to the chromatographic
      system and afforded a detection limit of 0.2 ng/mL. Good linearity was maintained
      over a wide concentration range (r2 > 0.994), and the accuracy was in the range
      of 86.6-114% for all the studied compounds. The precision, expressed in RSD%,
      ranged from 1.1% to 9.4% as intraday variability and less than 13% as interday
      precision for all of the analytes. The approach was applied to study the
      potential therapeutic mechanism of a well-known traditional Chinese medicine,
      Shao Fu Zhu Yu decoction. The results suggested that Shao Fu Zhu Yu decoction
      might protect against oxidative damage by increasing the concentrations of
      sulfhydryl compounds. Graphical abstract An approach to quantitatively
      determining sulfur compounds in the sulfur pathway simultaneously wasestablished
      and applied to the study of the effect of Shao Fu Zhu Yu decoction.

PMID- 29632972
TI  - [C5 palsy after multi-segmental cervical decompression : How can it be avoided?]
AB  - BACKGROUND: Anterior cervical discectomy and fusion (ACDF) as well as posterior
      instrumentation of the cervical spine are frequently performed surgeries for
      cervical disc prolapse or spinal stenosis. Surgery itself harbors a very low risk
      of adverse events. Postoperative palsy of the C5 nerve root, however, is a severe
      complication and its origin is still not fully understood. The risk of such a C5
      palsy is reported to be between 0 and 30%; 5% on average according to the
      literature. OBJECTIVES: To describe underlying pathomechanisms and to recommend
      strategies for risk reduction. MATERIALS AND METHODS: An extensive literature
      research via Medline was performed. RESULTS: Potential risk factors are male
      gender, sagittal diameter below 5.6 mm, anterior approach, and higher age.
      CONCLUSIONS: Currently available data only originates from retrospective or
      anatomical studies. A prospective register study with the goal to put light on
      the pathogenesis is currently being performed.

PMID- 29632973
TI  - [Primary fracture protheses and reverse shoulder arthroplasty in complex humeral
      head fractures : An alternative to joint-preserving osteosynthesis?]
AB  - BACKGROUND: The surgical management of complex humeral head fractures has adapted
      dynamically over the course of the last decade. The primary use of reverse
      shoulder arthroplasty in elderly patients has gained in relevance due to
      promising short and middle-term results. Long-term results, however, are still
      pending. The appliance of anatomical hemiarthroplasty, on the other hand, has
      lost in significance in favour of osteosynthesis and reverse shoulder
      arthroplasty. INDICATIONS: This review article follows the question as to under
      which circumstances primary fracture arthroplasty reflects an alternative or even
      a preference to joint-preserving osteosynthesis in the treatment of complex
      proximal humeral fractures. It also specifies spectrums of indications for
      anatomical hemiarthroplasty and reverse shoulder arthroplasty.

PMID- 29632974
TI  - [Surface modifications of implants. Part 1 : Material technical and biological
      principles].
AB  - The biological effects of implants in vivo are not only dependent on the
      implantation site and patient-specific factors but are also influenced by the
      physicochemical composition and the surface topography of the biomaterial. In
      cases of permanent implants applied to bone, primary stability, the promotion of
      rapid osteointegration and antimicrobial properties of the implant are strived
      for; however, surface modifications are also found on biomaterials which only
      temporarily come into contact with tissue. These include not only osteosynthesis
      materials, jig or implant templates but also surgical instruments. This article
      summarizes the relevant technical principles of materials for the assessment of
      implant surfaces. Besides technical material-specific and biological principles,
      different surface modifications for targeted clinical applications are presented.
      Furthermore, current developmental strategies are outlined.

PMID- 29632976
TI  - Do pulmonary findings of granulomatosis with polyangiitis respond to anti
      tuberculosis treatment?
AB  - Granulomatosis with polyangiitis (GPA) involves upper and lower respiratory
      tracts and kidneys. Lung involvement is among the most important organ
      involvements in GPA. GPA's lung involvement might be confused with other
      granulomatous conditions with lung involvement. In this report, we presented
      clinical features of two cases with GPA who had been diagnosed as tuberculosis
      (TBC) and well treated with anti-tuberculosis (anti-TBC) drugs. However, one of
      two cases had ear-nose-throat (ENT) manifestations before the diagnosis of TBC
      and her extrapulmonary findings related with GPA have added to clinical features
      in the following years. In the second case, the manifestations of GPA appeared
      after 13 months of anti-TBC treatment. We speculated that lung involvement in
      these cases may be due to GPA rather than TBC. Our aim was to highlight
      difficulties in the differential diagnosis between GPA and TBC and suggest the
      possible beneficial effect of anti-TBC drugs on the lung involvement due to GPA
      in light of the literature data.

PMID- 29632975
TI  - Agromyces mangrovi sp. nov., a Novel Actinobacterium Isolated from Mangrove Soil.
AB  - A novel, Gram-stain-positive, microaerophilic to aerobic, non-endospore-forming,
      no-motile and rod-shaped bacterium designated Q14T was isolated from mangrove
      soil samples collected on chengmai, Hainan province, China. Strain Q14T was able
      to grow at 10-40  degrees C (optimum 30  degrees C), pH 5.5-10.0 (optimum 6.5
      8.0) and with 0.5-6% (w/v) NaCl (optimum 1%). The genomic DNA G+C content was
      70.1%. The chemotaxonomic analysis showed that the predominant isoprenoid quinone
      was MK-12 and the major fatty acids were anteiso-C15:0, iso-C17:0 and anteiso
      C17:0. The major polar lipids of strain Q14T were diphosphatidylglycerol,
      phosphatidylglycerol and one glycolipid. The strain Q14T contained 2,4
      diaminobutylic acid (A2bu), alanine acid, glutamic acid and glycine in the
      peptidoglycans. The phylogenetic analysis and DNA-DNA hybridization, along with
      the phenotypic and chemotaxonomic characteristics, indicate that strain Q14T as a
      novel species of the genus Agromyces, for which the name Agromyces mangrovi sp.
      nov. is proposed. The type strain is Q14T (= MCCC 1K03191T = KCTC 39814T).

PMID- 29632977
TI  - Deformity correction with total knee arthroplasty for severe knee osteoarthritis
      accompanying extra-articular femoral deformity: the results are promising.
AB  - PURPOSE: This study aimed to evaluate patients with severe degenerative
      osteoarthritis of the knee and extra-articular femoral deformities treated with
      total knee arthroplasty (TKA) and acute deformity correction. METHODS: Ten
      patients with severe degenerative osteoarthritis of the knee and extra-articular
      femoral deformities were included, and the median age was 63 years (range 38-67).
      The etiology was post-traumatic malunion in four patients, rickets sequelae in
      four patients, and surgical sequelae due to multiple epiphyseal dysplasia in two
      patients. The severity of degenerative osteoarthritis and deformity analyses were
      assessed according to the Kellgren-Lawrence and Paley criteria, respectively. The
      median number of previous operations the patients had undergone was two (range 0
      3), and the median Oxford Knee Society score was 9 (range 5-13) before treatment.
      All patients were treated with primary TKA and deformity correction in the same
      surgery. The TKA was completed first, followed by an osteotomy at the apex of the
      deformity. Finally, a retrograde intramedullary nail was inserted. RESULTS: The
      median follow-up period was 44 (31-60) months. A stable and functional knee
      joint, a physiological mechanical axis, and solid osseous union were achieved in
      all patients. Late prosthetic failure was seen in one patient due to deep
      infection. The median Oxford Knee Society score was 42 (range 37-47) at the final
      follow-up. CONCLUSIONS: Combining several procedures in single setting for the
      treatment of severe knee osteoarthritis accompanied by extra-articular deformity
      may eliminate the need for multiple surgeries. Furthermore, a proper
      physiological mechanical axis can be obtained without causing substantial bone
      loss. LEVEL OF EVIDENCE: IV.

PMID- 29632978
TI  - The arthroscopic Bankart repair procedure enables complete quantitative labrum
      restoration in long-term assessments.
AB  - PURPOSE: The restoration of the labrum complex and the influence on secondary
      osteoarthritis after arthroscopic Bankart repair on magnetic resonance imaging
      (MRI) remain unclear. METHODS: Twenty-one patients were retrospectively followed
      after unilateral primary arthroscopic Bankart repair with knot-tying suture
      anchors (8.8 +/- 2.5 years after surgery, age 25.3 +/- 6.3 years). Bilateral
      structural MRI was performed to assess labrum-glenoid restoration by measurements
      of the labrum slope angle, height index, and labrum interior morphology according
      to the Randelli classification. Osteoarthritic status was bilaterally assessed by
      a modified assessment based on the Samilson-Prieto classification. RESULTS: MRI
      assessment revealed full labrum-glenoid complex restoration with equivalent
      parameters for anterior slope angle (mean +/- SD: 21.3 degrees  +/- 2.6 degrees 
      after Bankart repair vs. 21.9 degrees  +/- 2.6 degrees  control) and height index
      (2.34 +/- 0.4 vs. 2.44 +/- 0.4), as well as the inferior slope angle (23.1
      degrees  +/- 2.9 degrees  vs. 23.3 degrees  +/- 2.1 degrees ) and height index
      (2.21 +/- 0.3 vs. 2.21 +/- 0.3) (all n.s.). The labrum morphology showed only for
      the anterior labrum significant alterations (1.4 +/- 0.9 vs. 0.6 +/- 0.7, p <
      0.05), the inferior labrum occurred similarly (1.3 +/- 0.8 vs. 0.8 +/- 0.5,
      n.s.). Osteoarthritic changes were significantly increased after Bankart repair
      compared to the uninjured shoulder (4.8 +/- 5.1 mm vs. 2.5 +/- 1.0 mm; p < 0.05),
      with a significant correlation of osteoarthritis status between both shoulders (p
      < 0.05). Scores generally decreased after Bankart repair (constant 84.6 +/- 9.5
      vs. 94.5 +/- 4.9 control, p < 0.05; Rowe 84.5 +/- 6.5 vs. 96.2 +/- 4.2, p < 0.05;
      Walch-Duplay 82.4 +/- 7.0 vs. 94.3 +/- 4.0, p < 0.05) with a strong correlation
      with osteoarthritis status (p < 0.05). CONCLUSIONS: Arthroscopic Bankart repair
      enabled good clinical outcomes and complete quantitative labrum restoration
      parameters. Next to several well-known parameters, secondary osteoarthritis after
      arthroscopic Bankart repair significantly correlated with osteoarthritic status
      of the uninjured contralateral shoulder but was not influenced by quantitative
      labrum restoration. The recommendation for arthroscopic Bankart repair should be
      based on clinical parameters and not on prevention of secondary osteoarthritis.
      STUDY DESIGN: Case series. LEVEL OF EVIDENCE: IV.

PMID- 29632980
TI  - [Penile cancer].

PMID- 29632979
TI  - [Local treatment of penile cancer].
AB  - In recent decades, the local treatment of penile cancer has focused primary on
      the removal of the primary tumor. Due to the significant psycho-oncological
      effects of treating the primary tumor, the guidelines on penile cancer now
      contain a clear recommendation for preserving the target organ and prior to each
      surgical procedure histological examination should be performed to confirm the
      penile cancer. For more advanced tumors, reconstructive plastic surgery should
      also be considered. The treatment of the primary tumor should be based on the
      stage and the local extent and size of the tumor. The aim of this article is to
      highlight current standards in the local treatment of penile cancer.

PMID- 29632988
TI  - Small bowel obstruction and the gastrografin challenge.
AB  - The "gastrografin challenge" has been used for decades in the evaluation of small
      bowel obstruction (SBO). This type of study involves enteric administration of a
      water-soluble contrast followed by serial abdominal radiographs. While its
      diagnostic role is well established, its therapeutic role remains controversial.
      Following an algorithm for gastrografin challenge cases can help with
      interpretation. An understanding of the appearance of diluted contrast in the
      small bowel, the concentrating effect of contrast in the colon, and knowledge of
      surgical history and anatomy is paramount for diagnosis. In this article, we
      review the approach to acute SBO and the use of gastrografin along with reviewing
      image interpretation of cases of partial and complete SBO. Gastrografin use in
      adynamic ileus along with other potential future uses is also discussed.

PMID- 29632989
TI  - Advanced ultrasound applications in the assessment of renal transplants: contrast
      enhanced ultrasound, elastography, and B-flow.
AB  - Ultrasound is routinely used as the first imaging exam for evaluation of renal
      transplants and can identify most major surgical complications and evaluate
      vascularity with color Doppler. Ultrasound is limited, however, in the detection
      of parenchymal disease processes and Doppler evaluation is also prone to
      technical errors. Multiple new ultrasound applications have been developed and
      are under ongoing investigation which could add additional diagnostic capability
      to the routine ultrasound exam with minimal additional time, cost, and patient
      risk. Contrast-enhanced ultrasound (CEUS) can be used off-label in the transplant
      kidney, and can assist in detection of infection, trauma, and vascular
      complications. CEUS also can demonstrate perfusion of the transplant assessed
      quantitatively with generation of time-intensity curves. Future directions of
      CEUS include monitoring treatment response and microbubble targeted medication
      delivery. Elastography is an ultrasound application that can detect changes in
      tissue elasticity, which is useful to diagnose diffuse parenchymal disease, such
      as fibrosis, otherwise unrecognizable with ultrasound. Elastography has been
      successfully applied in other organs including the liver, thyroid, and breast;
      however, it is still under development for use in the transplant kidney. Unique
      properties of the transplant kidney including its heterogeneity, anatomic
      location, and other technical factors present challenges in the development of
      reference standard measurements. Lastly, B-flow imaging is a flow application
      derived from B-mode. This application can show the true lumen size of a vessel
      which is useful to depict vascular anatomy and bypasses some of the pitfalls of
      color Doppler such as demonstration of slow flow.

PMID- 29632990
TI  - Hepatopulmonary shunting on Tc99m-MAA liver mapping: correlation with dynamic
      cross-sectional imaging and description of different shunting patterns.
AB  - PURPOSE: The purpose of the study was to correlate lung shunt fraction (LSF)
      calculated by intra-arterial injection of Technetium-99m (Tc-99m)-labeled
      macroaggregated albumin (MAA) in a hepatic artery branch with the presence of
      certain patterns of vascular shunts on dynamic CT or MRI of the liver. METHODS:
      This retrospective study was approved by the institutional review board and
      informed consent was waived. We reviewed 523 MAA scans in 453 patients (301 men,
      152 women) performed from July 2007 to June 2015 and their correlative cross
      sectional imaging. Patterns of vascular shunts on dynamic CT or MRI performed
      within 3 months of the MAA study and that potentially divert hepatic arterial
      inflow to the systemic venous return were defined as "target shunts." Dynamic CT
      or MRI was classified into three groups with target shunt present, absent, or
      indeterminate. The mean LSF was compared across the first and second groups using
      paired t test. RESULTS: 342 CT and MRI studies met inclusion criteria: target
      shunts were present in 63 studies, absent in 271 studies, and 8 studies were
      indeterminate. When target shunts were visualized, the mean LSF on corresponding
      MAA scans was 12.9 +/- 10.36% (95% CI 10.29-15.15%) compared to 4.3 +/- 3.17%
      (95% CI 3.93-4.68%) when no target shunt was visualized. The difference was
      statistically significant (p value < 0.001). Identified target shunts were either
      direct (arteriohepatic venous shunt) or indirect (arterioportal shunt combined
      with a portosystemic shunt). CONCLUSIONS: Visualizing certain patterns of
      vascular shunting on a dynamic CT or MRI scan is associated with high LSF.

PMID- 29632991
TI  - Magnetic resonance imaging (MRI) of the renal sinus.
AB  - This article presents methods to improve MR imaging approach of disorders of the
      renal sinus which are relatively uncommon and can be technically challenging.
      Multi-planar Single-shot T2-weighted (T2W) Fast Spin-Echo sequences are
      recommended to optimally assess anatomic relations of disease. Multi-planar 3D
      T1W Gradient Recalled Echo imaging before and after Gadolinium administration
      depicts the presence and type of enhancement and relation to arterial, venous,
      and collecting system structures. To improve urographic phase MRI, concentrated
      Gadolinium in the collecting systems should be diluted. Diffusion-Weighted
      Imaging (DWI) should be performed before Gadolinium administration to minimize
      T2* effects. Renal sinus cysts are common but can occasionally be confused for
      dilated collecting system or calyceal diverticula, with the latter communicating
      with the collecting system and filling on urographic phase imaging. Vascular
      lesions (e.g., aneurysm, fistulas) may mimic cystic (or solid) lesions on non
      enhanced MRI but can be suspected by noting similar signal intensity to the blood
      pool and diagnosis can be confirmed with MR angiogram/venogram. Multilocular
      cystic nephroma commonly extends to the renal sinus, however, to date are
      indistinguishable from cystic renal cell carcinoma (RCC). Solid hilar tumors are
      most commonly RCC and urothelial cell carcinoma (UCC). Hilar RCC are
      heterogeneous, hypervascular with epicenter in the renal cortex compared to UCC
      which are centered in the collecting system, homogeneously hypovascular, and show
      profound restricted diffusion. Diagnosis of renal sinus invasion in RCC is
      critically important as it is the most common imaging cause of pre-operative
      under-staging of disease. Fat is a normal component of the renal sinus; however,
      amount of sinus fat correlates with cardiovascular disease and is also seen in
      lipomatosis. Fat-containing hilar lesions include lipomas, angiomyolipomas, and
      less commonly other tumors which engulf sinus fat. Mesenchymal hilar tumors are
      rare. MR imaging diagnosis is generally not possible, although anatomic relations
      should be described to guide diagnosis by percutaneous biopsy or surgery.

PMID- 29632992
TI  - Utility of the portal venous phase for diagnosing pancreatic necrosis in acute
      pancreatitis using the CT severity index.
AB  - PURPOSE: The purpose of the study was to evaluate the value of portal venous
      phase (PVP) images in the diagnosis of pancreatic necrosis in patients with acute
      pancreatitis using computed tomography severity index (CTSI). METHODS: This
      retrospective study was approved by our Institutional Review Board, and written
      informed consent was waived. Dynamic contrast-enhanced CT images, with the
      pancreatic parenchymal phase (PPP) and the PVP, were obtained from 56 consecutive
      patients with acute pancreatitis. Two radiologists reviewed two sets of images,
      namely PPP images alone (image set A) and combined PPP and PVP images (image set
      B) to evaluate the CTSI. Cases were categorized as necrotizing pancreatitis if
      ensuing walled-off necrosis formation was identified 4 weeks after onset of
      symptoms. The relationship between pancreatic necrosis and CTSI was compared
      between image sets A and B. Logistic regression analysis was performed to
      evaluate the significance of clinical and radiological factors associated with
      the diagnosis of pancreatic necrosis. RESULTS: Pancreatic necrosis was confirmed
      in 14 out of 56 (25%) patients. The area under the receiver-operating
      characteristic curve (AUC) for the diagnosis of pancreatic necrosis was 0.70 and
      0.78 for image sets A and B, respectively. The AUC for image set B was
      significantly greater than that for image set A (P = 0.0002). Logistic regression
      analysis demonstrated that among clinical and radiological factors tested, CTSI
      for image set B was independently correlated with pancreatic necrosis (P =
      0.025). CONCLUSIONS: Combined PPP and PVP images significantly improved the
      diagnostic accuracy of pancreatic necrosis following acute pancreatitis.

PMID- 29632993
TI  - Contrast-enhanced ultrasonography in interventional oncology.
AB  - Contrast-enhanced ultrasound (CEUS) has evolved from the use of agitated saline
      to second generation bioengineered microbubbles designed to withstand insonation
      with limited destruction. While only one of these newer agents is approved by the
      Food and Drug Administration for use outside echocardiography, interventional
      radiologists are increasingly finding off-label uses for ultrasound contrast
      agents. Notably, these agents have an extremely benign safety profile with no
      hepatic or renal toxicities and no radiation exposure. Alongside diagnostic
      applications, CEUS has begun to develop its own niche within the realm of
      interventional oncology. Certainly, the characterization of focal solid organ
      lesions (such as hepatic and renal lesions) by CEUS has been an important
      development. However, interventional oncologists are finding that the dynamic and
      real-time information afforded by CEUS can improve biopsy guidance, ablation
      therapy, and provide early evidence of tumor viability after locoregional
      therapy. Even more novel uses of CEUS include lymph node mapping and sentinel
      lymph node localization. Critical areas of research still exist. The purpose of
      this article is to provide a narrative review of the emerging roles of CEUS in
      interventional oncology.

PMID- 29632994
TI  - The bacterial replisome has factory-like localization.
AB  - DNA replication is essential to cellular proliferation. The cellular-scale
      organization of the replication machinery (replisome) and the replicating
      chromosome has remained controversial. Two competing models describe the
      replication process: In the track model, the replisomes translocate along the DNA
      like a train on a track. Alternately, in the factory model, the replisomes form a
      stationary complex through which the DNA is pulled. We summarize the evidence for
      each model and discuss a number of confounding aspects that complicate
      interpretation of the observations. We advocate a factory-like model for
      bacterial replication where the replisomes form a relatively stationary and
      weakly associated complex that can transiently separate.

PMID- 29632995
TI  - Efficacy and safety of trimodulin, a novel polyclonal antibody preparation, in
      patients with severe community-acquired pneumonia: a randomized, placebo
      controlled, double-blind, multicenter, phase II trial (CIGMA study).
AB  - PURPOSE: The CIGMA study investigated a novel human polyclonal antibody
      preparation (trimodulin) containing ~ 23% immunoglobulin (Ig) M, ~ 21% IgA, and ~
      56% IgG as add-on therapy for patients with severe community-acquired pneumonia
      (sCAP). METHODS: In this double-blind, phase II study (NCT01420744), 160 patients
      with sCAP requiring invasive mechanical ventilation were randomized (1:1) to
      trimodulin (42 mg IgM/kg/day) or placebo for five consecutive days. Primary
      endpoint was ventilator-free days (VFDs). Secondary endpoints included 28-day all
      cause and pneumonia-related mortality. Safety and tolerability were monitored.
      Exploratory post hoc analyses were performed in subsets stratified by baseline C
      reactive protein (CRP; >= 70 mg/L) and/or IgM (<= 0.8 g/L). RESULTS: Overall,
      there was no statistically significant difference in VFDs between trimodulin
      (mean 11.0, median 11 [n = 81]) and placebo (mean 9.6; median 8 [n = 79]; p =
      0.173). Twenty-eight-day all-cause mortality was 22.2% vs. 27.8%, respectively (p
      = 0.465). Time to discharge from intensive care unit and mean duration of
      hospitalization were comparable between groups. Adverse-event incidences were
      comparable. Post hoc subset analyses, which included the majority of patients (58
      78%), showed significant reductions in all-cause mortality (trimodulin vs.
      placebo) in patients with high CRP, low IgM, and high CRP/low IgM at baseline.
      CONCLUSIONS: No significant differences were found in VFDs and mortality between
      trimodulin and placebo groups. Post hoc analyses supported improved outcome
      regarding mortality with trimodulin in subsets of patients with elevated CRP,
      reduced IgM, or both. These findings warrant further investigation. TRIAL
      REGISTRATION: NCT01420744.

PMID- 29632998
TI  - [Epigenetics: more interesting than relevant for clinicians?]

PMID- 29632997
TI  - Human-relevant potency threshold (HRPT) for ERalpha agonism.
AB  - The European Commission has recently proposed draft criteria for the
      identification of endocrine disrupting chemicals (EDCs) that pose a significant
      hazard to humans or the environment. Identifying and characterizing toxic hazards
      based on the manner by which adverse effects are produced rather than on the
      nature of those adverse effects departs from traditional practice and requires a
      proper interpretation of the evidence regarding the chemical's ability to produce
      physiological effect(s) via a specific mode of action (MoA). The ability of any
      chemical to produce a physiological effect depends on its pharmacokinetics and
      the potency by which it acts via the various MoAs that can lead to the particular
      effect. A chemical's potency for a specific MoA-its mechanistic potency-is
      determined by two properties: (1) its affinity for the functional components that
      comprise the MoA, i.e., its specific receptors, enzymes, transporters,
      transcriptional elements, etc., and (2) its ability to alter the functional state
      of those components (activity). Using the agonist MoA via estrogen receptor
      alpha, we illustrate an empirical method for determining a human-relevant potency
      threshold (HRPT), defined as the minimum level of mechanistic potency necessary
      for a chemical to be able to act via a particular MoA in humans. One important
      use for an HRPT is to distinguish between chemicals that may be capable of,
      versus those likely to be incapable of, producing adverse effects in humans via
      the specified MoA. The method involves comparing chemicals that have different
      ERalpha agonist potencies with the ability of those chemicals to produce ERalpha
      mediated agonist responses in human clinical trials. Based on this approach, we
      propose an HRPT for ERalpha agonism of 1E-04 relative to the potency of the
      endogenous estrogenic hormone 17beta-estradiol or the pharmaceutical estrogen,
      17alpha-ethinylestradiol. This approach provides a practical way to address
      Hazard Identification according to the draft criteria for identification of EDCs
      recently proposed by the European Commission.

PMID- 29632999
TI  - MR-based radiomics signature in differentiating ocular adnexal lymphoma from
      idiopathic orbital inflammation.
AB  - OBJECTIVES: To assess the value of the MR-based radiomics signature in
      differentiating ocular adnexal lymphoma (OAL) and idiopathic orbital inflammation
      (IOI). METHODS: One hundred fifty-seven patients with pathology-proven OAL (84
      patients) and IOI (73 patients) were divided into primary and validation cohorts.
      Eight hundred six radiomics features were extracted from morphological MR images.
      The least absolute shrinkage and selection operator (LASSO) procedure and linear
      combination were used to select features and build radiomics signature for
      discriminating OAL from IOI. Discriminating performance was assessed by the area
      under the receiver-operating characteristic curve (AUC). The predictive results
      were compared with the assessment of radiologists by chi-square test. RESULTS:
      Five radiomics features were included in the radiomics signature, which
      differentiated OAL from IOI with an AUC of 0.74 and 0.73 in the primary and
      validation cohorts respectively. There was a significant difference between the
      classification results of the radiomics signature and those of a radiology
      resident (p < 0.05), although there was no significant difference between the
      results of the radiomics signature and those of a more experienced radiologist (p
      > 0.05). CONCLUSIONS: Radiomics features have the potential to differentiate OAL
      from IOI. KEY POINTS: * Clinical and imaging findings of OAL and IOI often
      overlap, which makes diagnosis difficult. * Radiomics features can potentially
      differentiate OAL from IOI non invasively. * The radiomics signature
      discriminates OAL from IOI at the same level as an experienced radiologist.

PMID- 29633000
TI  - Inter-operator variability and source of errors in tumour response assessment for
      hepatocellular carcinoma treated with sorafenib.
AB  - OBJECTIVES: To assess the inter-operator concordance and the potential sources of
      discordance in defining response to sorafenib in hepatocellular carcinoma (HCC).
      METHODS: All patients who received sorafenib between September 2008 and February
      2015 were scrutinised for this retrospective study. Images were evaluated
      separately by three radiologists with different expertise in liver imaging
      (operator 1, >10 years; operator 2, 5 years; operator 3, no specific training in
      liver imaging), according to: response evaluation radiological criteria in solid
      tumours (RECIST) 1.1, modified RECIST (mRECIST) and response evaluation criteria
      in cancer of the liver (RECICL). RESULTS: The overall response concordance
      between the more expert operators was good, irrespective of the criteria (RECIST
      1.1, K = 0.840; mRECIST, K = 0.871; RECICL, K = 0.819). Concordance between the
      less expert operator and the other colleagues was lower. The most evident
      discordance was in target lesion response assessment, with expert operators
      disagreeing mostly on lesion selection and less expert operators on lesion
      measurement. As a clinical correlate, overall survival was more tightly related
      with "progressive disease" as assessed by the expert compared to the same
      assessment performed by operator 3. CONCLUSIONS: Decision on whether a patient is
      a responder or progressor under sorafenib may vary among different operators,
      especially in case of a non-specifically trained radiologist. Regardless of the
      adopted criteria, patients should be evaluated by experienced radiologists to
      minimise variability in this critical instance. KEY POINTS: * Inter-operator
      variability in the assessment of response to sorafenib is poorly known. * The
      concordance between operators with expertise in liver imaging was good. * Target
      lesions selection was the main source of discordance between expert operators. *
      Concordance with non-specifically trained operator was lower, independently from
      the response criteria. * The non-specifically trained operator was mainly
      discordant in measurements of target lesions.

PMID- 29633001
TI  - CT diagnosis of gallbladder adenomyomatosis: importance of enhancing mucosal
      epithelium, the "cotton ball sign".
AB  - OBJECTIVES: To determine the diagnostic value of the cotton ball sign and other
      CT features in patients with gallbladder (GB) wall thickenings (WTs). METHODS:
      Three blinded readers reviewed the preoperative CT and MR images of 101 patients
      with pathologically confirmed GB adenomyomatosis (GA) (n = 34) and other benign
      (n = 29), malignant (n = 41), and premalignant (n = 2) GBWTs. Three readers
      analysed the morphological features of GBWT and presence of the "cotton ball
      sign", defined as fuzzy grey dots in GBWT or a dotted outer border of the inner
      enhancing layer on contrast-enhanced (CE) CT. In addition, the "pearl necklace
      sign" on MR was analysed. RESULTS: In the GA group (n = 34), prevalence of the
      cotton ball sign and pearl necklace sign was 74% (25/34) and 44% (15/34),
      respectively. Presence of the cotton ball sign, smooth contour of the mucosa,
      double-layering enhancement, and enhancement degree weaker than the renal cortex
      on CT images were significant predictors of benign GBWT (p < 0.01). When
      differentiating GA from GB malignancy or premalignancy, accuracy of the cotton
      ball sign and pearl necklace sign was 81% (62/77) and 74% (57/77), respectively.
      CONCLUSION: The cotton ball sign on CE-CT showed higher sensitivity and
      comparable specificity to those of the pearl necklace sign in differentiating GA
      from malignancy. KEY POINTS: * Prevalence of the cotton ball sign on CT was 74%
      in gallbladder adenomyomatosis. * The cotton ball sign was useful in
      differentiating gallbladder adenomyomatosis from gallbladder cancer. * The cotton
      ball sign was more sensitive than the pearl necklace sign for adenomyomatosis
      diagnosis.

PMID- 29633002
TI  - Identification of high-risk plaque features in intracranial atherosclerosis:
      initial experience using a radiomic approach.
AB  - OBJECTIVES: To evaluate a quantitative radiomic approach based on high-resolution
      magnetic resonance imaging (HR-MRI) to differentiate acute/sub-acute symptomatic
      basilar artery plaque from asymptomatic plaque. METHODS: Ninety-six patients with
      basilar artery stenosis underwent HR-MRI between January 2014 and December 2016.
      Patients were scanned with T1- and T2-weighted imaging, as well as T1 imaging
      following gadolinium-contrast injection (CE-T1). The stenosis value, plaque
      area/burden, lumen area, minimal luminal area (MLA), intraplaque haemorrhage
      (IPH), contrast enhancement ratio and 94 quantitative radiomic features were
      extracted and compared between acute/sub-acute and asymptomatic patients. Multi
      variate logistic analysis and a random forest model were used to evaluate the
      diagnostic performance. RESULTS: IPH, MLA and enhancement ratio were
      independently associated with acute/subacute symptoms. Radiomic features in T1
      and CE-T1 images were associated with acute/subacute symptoms, but the features
      from T2 images were not. The combined IPH, MLA and enhancement ratio had an area
      under the curve (AUC) of 0.833 for identifying acute/sub-acute symptomatic
      plaques, and the combined T1 and CE-T1 radiomic approach had a significantly
      higher AUC of 0.936 (p = 0.01). Combining all features achieved an AUC of 0.974
      and accuracy of 90.5%. CONCLUSIONS: Radiomic analysis of plaque texture on HR-MRI
      accurately distinguished between acutely symptomatic and asymptomatic basilar
      plaques. KEY POINTS: * High-resolution magnetic resonance imaging can assess
      basilar artery atherosclerotic plaque. * Radiomic features in T1 and CE-T1 images
      are associated with acute symptoms. * Radiomic analysis can accurately
      distinguish between acute symptomatic and asymptomatic plaque. * The highest
      accuracy may be achieved by combining radiomic and conventional features.

PMID- 29633003
TI  - Facial nerve tractography: A new tool for the detection of perineural spread in
      parotid cancers.
AB  - OBJECTIVES: To determine whether facial nerve MR tractography is useful in
      detecting PeriNeural Spread in parotid cancers. METHODS: Forty-five participants
      were enrolled. Thirty patients with surgically managed parotid tumors (15
      malignant, 15 benign) were compared with 15 healthy volunteers. All of them had
      undergone 3T-MRI with diffusion acquisition and post-processing constrained
      spherical deconvolution-based tractography. Parameters of diffusion-weighted
      sequences were b-value 1,000 s/mm2, 32 directions. Two radiologists performed a
      blinded visual reading of tractographic maps and graded the facial nerve average
      pathlength and fractional anisotropy (FA). We also compared diagnostic accuracy
      of tractography with morphological MRI sequences to detect PeriNeural Spread. Non
      parametric methods were used. RESULTS: Average pathlength was significantly
      higher in cases with PeriNeural Spread (39.86 mm [Quartile1: 36.27; Quartile3:
      51.19]) versus cases without (16.23 mm [12.90; 24.90]), p<0.001. The threshold
      above which there was a significant association with PeriNeural Spread was set at
      27.36 mm (Se: 100%; Sp: 84%; AUC: 0.96, 95% CI 0.904-1). There were no
      significant differences in FA between groups. Tractography map visual analyses
      directly displayed PeriNeural Spread in distal neural ramifications with
      sensitivity of 75%, versus 50% using morphological sequences. CONCLUSIONS:
      Tractography could be used to identify facial nerve PeriNeural Spread by parotid
      cancers. KEY POINTS: * Tractography could detect facial nerve PeriNeural Spread
      in parotid cancers. * The average pathlength parameter is increased in case of
      PeriNeural Spread. * Tractography could map PeriNeural Spread more precisely than
      conventional imaging.

PMID- 29633005
TI  - A phase II study of modified FOLFIRINOX for chemotherapy-naive patients with
      metastatic pancreatic cancer.
AB  - BACKGROUND: We evaluated the efficacy and safety of a modified FOLFIRINOX regimen
      for chemotherapy-naive patients with metastatic pancreatic cancer. METHODS:
      Patients with untreated metastatic pancreatic cancer (MPC) received modified
      FOLFIRINOX (intravenous oxaliplatin 85 mg/m2, irinotecan 150 mg/m2, 5-FU infusion
      2400 mg/m2 over 46 h, no bolus 5-FU). The primary endpoints were overall survival
      and the incidence of grade 3 or higher neutropenia. No patients received
      prophylactic pegfilgrastim. RESULTS: Sixty-nine pts. were enrolled from 39
      institutions in Japan. The median overall survival was 11.2 months [95%
      confidence interval (CI) 9.0-]. The median progression-free survival was 5.5
      months (95% CI 4.1-6.7). The response rate was 37.7% (95% CI 26.3-50.2), and the
      disease control rate was 78.3% (95% CI 66.7-87.3). The incidence of grade 3 or
      higher neutropenia was 47.8%. Serious adverse events occurred in six patients
      (8.7%). All AE proportions were less than those in the previous Japanese full
      dose phase II study. One patient died due to interstitial pneumonia related to
      treatment. CONCLUSION: This is the first prospective study of modified FOLFIRINOX
      in Asia. Modified FOLFIRINOX in this study has an improved safety profile with
      maintained efficacy in MPC without prophylactic pegfilgrastim.

PMID- 29633004
TI  - Multiparametric MRI for Suspected Recurrent Prostate Cancer after HIFU:Is DCE
      still needed?
AB  - PURPOSE: To assess the added value of the dynamic contrast-enhanced sequence
      (DCE) to combination T2-weighted imaging (T2w) + diffusion-weighted imaging (DWI)
      in detecting prostate cancer (PCa) recurrence after HIFU (high-intensity focused
      ultrasound). METHODS: Forty-five males with clinical and biological suspected PCa
      recurrence were retrospectively selected. All underwent multi-parametric MRI
      (mpMRI) before biopsies. Two readers independently assigned a Likert score of
      cancer likelihood on T2w + DWI + DCE and T2w + DWI images. Prostatic biopsies
      were taken as the gold standard. RESULTS: Recurrent PCa was identified at biopsy
      for 37 patients (82%). Areas under the receiver-operating curve of T2w + DWI and
      T2w + DWI + DCE imaging were not significantly different for both readers. Using
      a Likert score >= 3 for the PCa diagnosis threshold, sensitivity at the lobe
      level for the (1) senior and (2) junior reader for T2w +DWI +DCE sensitivity was
      (1) 0.97 and (2) 0.94 vs. (1) 0.94 and (2) 0.97 for T2w + DWI. CONCLUSION:
      Accuracy of mpMRI was not significantly improved by adding DCE to T2w + DWI.
      Sensitivity was high for T2w + DWI + DCE and T2w + DWI with no significant
      difference for either the junior or senior reader. KEY POINTS: * MpMRI has the
      capability to detect PCa recurrence in post-HIFU monitoring. * The sensitivity of
      T2w and DWI for detecting PCa recurrence was not improved by DCE. * Readers with
      different degrees of experience did not improve their performance with DCE.

PMID- 29633006
TI  - Multikinase inhibitor sorafenib induces skin toxicities in tumor-bearing mice.
AB  - OBJECTIVES: To investigate the pathologic changes and pathogenesis of multikinase
      inhibitor (MKI)-induced skin lesions in an animal model. METHODS: Tumor-bearing
      nude mice and BDF1 mice were treated with different doses (30-240 mg/kg, Bid) of
      sorafenib. The pathology and severity of the skin lesions was assessed and
      evaluated. The concentration of sorafenib in the skin was also determined.
      RESULTS: Sorafenib transiently induced skin rash at high doses (120-240 mg/kg).
      The induced skin lesions had pathological manifestations resembling the
      observations in human patients. The skin of mice treated with sorafenib had
      significantly increased pathological scores and thickness of the stratum spinosum
      compared with the control, and induced more severe cutaneous lesions in nude mice
      than in BDF1 mice. The severity of skin lesions was correlated with the local
      concentration of sorafenib in the skin, which was significantly higher in nude
      mice than in BDF1 mice. Sorafenib treatment significantly increased the
      expression of F4-80, Ly6G, tumor growth factor (TGF)-1beta, Smad2/3, alpha-smooth
      muscle actin, and proliferating cell nuclear antigen. CONCLUSIONS: The severity
      of skin lesions was positively correlated with the concentration of sorafenib in
      the skin. Our results suggested the involvement of the TGF-beta1/Smads signaling
      pathway in the skin reaction induced by MKIs.

PMID- 29633007
TI  - The source of cell-free mitochondrial DNA in trauma and potential therapeutic
      strategies.
AB  - Mitochondria play a key role in the pathophysiology of post-injury inflammation.
      Cell-free mitochondrial DNA (cf-mtDNA) is now understood to catalyse sterile
      inflammation after trauma. Observations in trauma cohorts have identified high cf
      mtDNA in patients with systemic inflammatory response syndrome and multiple organ
      failure as well as following major surgery. The source of cf-mtDNA can be various
      cells affected by mechanical and hypoxic injury (passive mechanism) or induced by
      inflammatory mechanisms (active mechanism). Multiple forms of cf-mtDNA exist;
      mtDNA fragments, mtDNA in microparticles/vesicles and cell-free mitochondria.
      Trauma to cells that are rich in mitochondria are believed to release more cf
      mtDNA. This review describes the current understanding of the mechanisms of cf
      mtDNA release, its systemic effects and the potential therapeutic implications
      related to its modification. Although current understanding is insufficient to
      change trauma management, focussed research goals have been identified to pave
      the way for monitoring and manipulation of cf-mtDNA release and effects in
      trauma.

PMID- 29633009
TI  - Time dependency of the SNARC effect for different number formats: evidence from
      saccadic responses.
AB  - In line with the suggestion that the strength of the spatial numerical
      association of response codes (SNARC) effect was time dependent, the aim of the
      present study was to assess whether the association strength depends on the
      processing time of numerical quantity and/or of the time to initiate responses.
      More specifically, we examined whether and how the SNARC effect could be
      modulated by number format and effector type. Experiment 1 compared the effect
      induced by Arabic numbers and number words on the basis of saccadic responses in
      a parity judgment task. Indeed, previous studies have shown that Arabic numbers
      lead to faster processing than number words. The results replicated the SNARC
      effect with Arabic numbers, but not with number words. Experiment 2 was similar
      to Experiment 1, but this time manual responses (i.e., responses far slower than
      saccadic ones) were recorded. A strong SNARC effect was observed for both number
      formats. Further analyses revealed a correlation between mean individual response
      times and the strength of the SNARC effect. We proposed that the initiation times
      for saccadic responses may be too short for the SNARC effect to appear, in
      particular with the written number format for which activation of magnitude takes
      time. We conclude in terms of time variations resulting from processing
      specificities related with number format, effector type and also individual
      reaction and processing speed.

PMID- 29633008
TI  - Comorbidities, repeated hospitalizations, and age >= 80 years as indicators of
      anemia development in the older population.
AB  - Anemia represents a common condition among the elderly; however, its prevalence
      and causes are not well known. This retrospective analysis was performed on 981
      patients aged >= 60 in Poland over 2013-2014. The prevalence of anemia was 17.2%
      and increased with age. The predominant causes of anemia were the following:
      anemia of chronic disease (33.1%), unexplained anemia (28.4%), deficiency anemia
      (22.5%, including iron deficiency 13%), and chemo-/radiotherapy-induced anemia
      (8.9%). In the multivariate logistic regression model, factors increasing the
      risk of anemia were the following: age >= 80 years (OR 2.29; 95%CI 1.19-4.42; P =
      0.013), the number of comorbidities (two diseases OR 2.85; 95%CI 1.12-7.30; P =
      0.029, three diseases OR 6.28; 95%CI 2.22-17.76; P = 0.001, four diseases OR
      4.64; 95%CI 1.27-17.01; P = 0.021), and hospitalizations (OR 1.34; 95%CI 1.13
      1.58; P = 0.001). After a 2-year follow-up, the cumulative survival among
      patients without anemia in relation to the group with anemia was 90.76 vs. 78.08%
      (P < 0.001). In the multivariate model, anemia (HR 3.33, 95%CI 1.43-7.74, P =
      0.005), heart failure (HR 2.94, 95%CI 1.33-6.50, P = 0.008), and cancer (HR 3.31,
      95%CI 1.47-7.49, P < 0.004) were all significantly correlated with mortality. In
      patients >= 60 years, the incidence of anemia increases with age, number of
      comorbidities, and frequency of hospitalizations and has an adverse impact on
      survival.

PMID- 29633010
TI  - Evaluation of combined growth media for in vitro cultivation of oropharyngeal
      biofilms on prosthetic silicone.
AB  - In the upper aerodigestive tract, biofilm deposits by oropharyngeal microbes can
      cause failure of medical polymer devices like voice prostheses. Previous studies
      on testing of inhibitive strategies still lack of comparability due to varying
      study protocols concerning growth media, microbial species and growth conditions.
      Goal of the study was therefore to test cultivation of a mixed biofilm of
      isolated oropharyngeal microbes under in vitro growth conditions using mixtures
      of common growth media. Mixtures of yeast peptone dextrose medium (YPD), fetal
      bovine serum (FBS), RPMI 1640, Yeast nitrogen base medium (YNB) and brain heart
      infusion (BHI) were tested to grow mixed biofilm deposits of Candida albicans,
      Candida tropicalis, Staphylococcus aureus, Streptococcus epidermidis, Rothia
      dentocariosa and Lactobacillus gasseri on medical grade silicone. Periodic
      assessment of living biofilm was performed over 22 days by a digital microscope
      and the cultivated biofilm structures were analyzed by scanning electron
      microscopy after completion of the study. Mixtures of BHI, YPD and FBS improved
      microscopic growth of multispecies biofilm deposits over time, while addition of
      RPMI and YNB resulted in reduction of visible biofilm deposit sizes. A mixtures
      of FBS 30% + YPD 70% and BHI 30% + YPD 70% showed enhanced support of permanent
      surface growth on silicone. Growth kinetics of in vitro multispecies biofilms can
      be manipulated by using mixtures of common growth media. Using mixtures of growth
      media can improve growth of longterm multispecies oropharyngeal biofilm models
      used for in vitro testing of antibiofilm materials or coatings for voice
      prostheses.

PMID- 29633011
TI  - Gluten-free-rendered products contribute to imbalanced diets in children and
      adolescents with celiac disease.
AB  - PURPOSE: As well as adhering to the safe limit for gluten intake, a suitable
      gluten-free (GF) diet must also be nutritionally balanced. However, malnutrition
      has been observed in the population with celiac disease (CD). This is even more
      important in the case of children and adolescents, whose GF diet must also ensure
      their proper growth. The aim of the present study was to assess the diet quality
      of children and adolescents with CD to attain optimal nutritional status,
      determining the most relevant factors that affect a balanced diet. METHODS:
      Eighty-three children and adolescents with CD (9.2 +/- 3.8 years) took part in
      the study. Height, weight and body composition were measured. An analysis of
      energy consumption and of the macronutrient distribution of their diet was
      carried out. Adherence to Mediterranean diet by KIDMED index was analyzed, and
      energy and nutrients intake. RESULTS: The diet of participants was not balanced,
      containing more fat and less carbohydrate than recommended. Most children and
      adolescents revealed adequate body mass index and suitable body fat percentage.
      Two-thirds of them showed moderate or poor KIDMED index, the case of girls being
      remarkable. When the GF diet, containing GF-rendered foodstuffs, was compared to
      a similar type of diet but substituting GF products with their analogs containing
      gluten, important nutritional differences were revealed. CONCLUSIONS: Even though
      celiac children and adolescents' diet is unhealthy due to its inappropriate
      dietary pattern, following a diet based on GF products raises extra difficulty in
      complying with the nutritional recommendations.

PMID- 29633012
TI  - CANOMAD and other chronic ataxic neuropathies with disialosyl antibodies (CANDA).
AB  - INTRODUCTION: CANOMAD/CANDA are syndromes characterized by ataxic neuropathy,
      ophthalmoplegia, monoclonal gammopathy, cold agglutinins and disialosyl
      antibodies. METHODS: A retrospective review of our neuromuscular autoantibody
      panel database was performed. Anti-GD1b seropositive patients with ataxia were
      included. RESULTS: Eleven patients were identified. Median age at onset was 56
      years. Median disease duration was 6 years. All patients had gait disorders. Nine
      had ocular motility abnormalities. Most had a monoclonal protein and all had
      elevated serum IgM. Electrodiagnostic studies showed a mixed axonal/demyelinating
      pattern (6), an axonal pattern (4), or a pure demyelinating pattern (1).
      Ultrasounds showed nerve enlargement patterns consistent with acquired
      demyelination. A nerve biopsy showed near complete loss of myelinated axons with
      preservation of smaller axons. Rituximab was the most effective immunotherapy.
      CONCLUSION: CANOMAD/CANDA are rare and debilitating disorders with characteristic
      clinical and diagnostic findings. In our cohort, nerve ultrasound showed regional
      nerve enlargement and rituximab was the most effective immunomodulatory therapy.

PMID- 29633013
TI  - Clinical impact of intratumoral HER2 heterogeneity on trastuzumab efficacy in
      patients with HER2-positive gastric cancer.
AB  - BACKGROUND: There is growing interest in the clinical significance of
      intratumoral HER2 heterogeneity. Its prognostic and predictive impacts on
      trastuzumab efficacy were demonstrated in breast cancer. However, its clinical
      significance in gastric cancer is still unclear. METHODS: Twenty-eight HER2
      positive gastric cancer patients who had gastrectomy prior to trastuzumab-based
      chemotherapy were consecutively enrolled. Intratumoral HER heterogeneity was
      evaluated using whole-tissue sections by immunohistochemistry. When all tumor
      cells overexpressed HER2 protein, the tumor was defined as homogeneously HER2
      (Homo-HER2)-positive group. The others were defined as heterogeneously HER2
      (Hetero-HER2)-positive group. RESULTS: There was no significant difference in
      clinicopathological features between the two groups. The median progression-free
      survival (PFS) and overall survival (OS) in the Homo-HER2-positive group were
      significantly longer than those in the Hetero-HER2-positive group (PFS; 20.0
      months [95% CI 17.8-22.2] vs. 6.0 months [95% CI 2.3-9.7]; HR 0.11; 95% CI 0.03
      0.41; p < 0.001, OS; not reached vs. 14.0 months [95% CI 11.9-16.1]; HR 0.18; 95%
      CI 0.06-0.61; p = 0.003). In the multivariate analysis, these associations
      remained significant both in PFS (HR 0.12; 95% CI 0.03-0.46, p = 0.002) and OS
      (HR 0.21; 95% CI 0.06-0.72, p = 0.013). With respect to response rate, no
      statistical difference was found between two groups. However, deeper tumor
      shrinkage was obtained in the Homo-HER2-positive group compared with the Hetero
      HER2-positive group (p = 0.046). CONCLUSIONS: Intratumoral HER2 heterogeneity may
      have robust clinical impact on trastuzumab efficacy in patients with HER2
      positive gastric cancer. These findings should be validated by larger independent
      cohorts and further molecular correlative analyses are warranted.

PMID- 29633014
TI  - Living interfaces watched with new tools.

PMID- 29633015
TI  - Expression of IL33 and IL35 in oral lichen planus.
AB  - Oral lichen planus (OLP) is a complex immunological disorder, mediated in part by
      the release of cytokines by activated T-cells. Recently, the role of novel
      cytokines including IL33 and IL35 has been described in various chronic
      inflammatory diseases. IL33, a member of the IL-1 superfamily of cytokines,
      functions as an 'alarmin' released after cell necrosis to alert the immune system
      to tissue damage or stress. IL35, a member of IL12 cytokine family, is produced
      by regulatory T-cells and suppresses the immune response. The expression of IL33
      and IL35 is yet to be investigated in OLP. The aim of this study was to determine
      the presence and topographical distribution of IL33 and IL35 in OLP using
      immunohistochemistry and quantitative real-time reverse transcriptase polymerase
      chain reaction (qPCR). For IHC, formalin-fixed paraffin-embedded archival
      specimens of OLP (n = 10) and a non-specific inflammatory (NSI) control group (n
      = 9) were used. A double-labelling immunofluorescence technique was used to
      determine the expression of IL33 and IL35 on CD3+ T-cells. In addition, 12 fresh
      tissue samples (OLP n = 6 and NSI controls n = 6) were used to determine the gene
      expression of IL33 and EBI3 (one chain of the dimeric IL35). Quantitative and
      qualitative analysis was performed with statistical significance set at p < 0.05.
      IHC showed positive immunostaining with IL33 and IL35 in both OLP and NSI.
      Comparison of the numbers of IL33+ and IL35+ cells in OLP and NSI did not show
      any significant difference. In OLP, there were significantly more IL33+ cells in
      the deeper connective tissue region than at the epithelial-connective tissue
      interface. Interestingly, all IL35+ cells observed in both OLP and NSI tissues
      showed ovoid/plasmacytoid morphology. Double-labelling immunofluorescence showed
      that IL33 and IL35 expression was not localized within CD3+ T-cells. The gene
      expression experiments showed significantly higher expression of EBI3 (fold
      regulation 14.02) in OLP when compared to the inflammatory controls. IL33 gene
      expression was not different between the groups. However, within the OLP tissues,
      there was a significantly higher expression of IL33 than EBI3. Our data
      demonstrate the expression of IL33 and IL35 in OLP lesions. Further studies are
      needed to understand the functional role of these cytokines in OLP pathogenesis.

PMID- 29633016
TI  - Delay in weight bearing in surgically treated tibial shaft fractures is
      associated with impaired healing: a cohort analysis of 166 tibial fractures.
AB  - BACKGROUND: The relation between timing of weight bearing after a fracture and
      the healing outcome is yet to be established, thereby limiting the implementation
      of a possibly beneficial effect for our patients. The current study was
      undertaken to determine the effect of timing of weight bearing after a surgically
      treated tibial shaft fracture. MATERIALS AND METHODS: Surgically treated
      diaphyseal tibial fractures were retrospectively studied between 2007 and 2015.
      The timing of initial weight bearing (IWB) was analysed as a predictor for
      impaired healing in a multivariate regression. RESULTS: Totally, 166 diaphyseal
      tibial fractures were included, 86 cases with impaired healing and 80 with normal
      healing. The mean age was 38.7 years (range 16-89). The mean time until IWB was
      significantly shorter in the normal fracture healing group (2.6 vs 7.4 weeks, p <
      0.001). Correlation analysis yielded four possible confounders: infection
      requiring surgical intervention, fracture type, fasciotomy and open fractures.
      Logistic regression identified IWB as an independent predictor for impaired
      healing with an odds ratio of 1.13 per week delay (95% CI 1.03-1.25).
      CONCLUSIONS: Delay in initial weight bearing is independently associated with
      impaired fracture healing in surgically treated tibial shaft fractures. Unlike
      other factors such as fracture type or soft tissue condition, early resumption of
      weight bearing can be influenced by the treating physician and this factor
      therefore has a direct clinical relevance. This study indicates that early
      resumption of weight bearing should be the treatment goal in fracture fixation.
      LEVEL OF EVIDENCE: 3b.

PMID- 29633018
TI  - Diversity of the genus Bunodera Railliet, 1896 (Trematoda: Allocreadiidae) in the
      northern part of Eastern Europe and North-eastern Asia, estimated from 28S rDNA
      sequences, with a description of Bunodera vytautasi sp. nov.
AB  - Phylogenetic relationship reconstruction and taxonomical analysis of trematodes
      of the genus Bunodera was carried out using 28S rDNA partial sequences along with
      a description and molecular characterisation of a new species, B. vytautasi sp.
      nov. A new species is reported from the intestine of Pungitius pungitius
      (Linnaeus, 1758), collected from Magadan Region, Russia. The diagnostic
      characters of B. vytautasi sp. nov. are the extension of vitelline fields from
      the oral sucker or posterior edge of the pharynx to the posterior extremity of
      the body, the confluence of vitelline fields within the forebody, the extension
      of the cirrus-sac to the posterior third of ventral sucker or further backwards
      with an outlet beyond the posterior edge of the sucker, and the presence of a
      unipartite internal seminal vesicle. Both Bayesian and Maximum Likelihood trees
      shared the same tree topology, in which the genus Bunodera was shown to be
      monophyletic. Representatives of the genus Bunodera were distributed into three
      well-supported clades: percid-infecting species (Eurasian species B. luciopercae
      and B. acerinae and North American B. luciopercae s.l.), gasterosteid-infecting
      species (amphi-Pacific B. mediovitellata and North American B. inconstans and B.
      eucaliae) and percid/gasterosteid-infecting species (Asiatic B. vytautasi sp.
      nov. and North American B. sacculata). Eurasian B. luciopercae and B. acerinae
      were more closely related to each other than to North American B. luciopercae
      s.l.

PMID- 29632996
TI  - Resolved versus confirmed ARDS after 24 h: insights from the LUNG SAFE study.
AB  - PURPOSE: To evaluate patients with resolved versus confirmed ARDS, identify
      subgroups with substantial mortality risk, and to determine the utility of day 2
      ARDS reclassification. METHODS: Our primary objective, in this secondary LUNG
      SAFE analysis, was to compare outcome in patients with resolved versus confirmed
      ARDS after 24 h. Secondary objectives included identifying factors associated
      with ARDS persistence and mortality, and the utility of day 2 ARDS
      reclassification. RESULTS: Of 2377 patients fulfilling the ARDS definition on the
      first day of ARDS (day 1) and receiving invasive mechanical ventilation, 503
      (24%) no longer fulfilled the ARDS definition the next day, 52% of whom initially
      had moderate or severe ARDS. Higher tidal volume on day 1 of ARDS was associated
      with confirmed ARDS [OR 1.07 (CI 1.01-1.13), P = 0.035]. Hospital mortality was
      38% overall, ranging from 31% in resolved ARDS to 41% in confirmed ARDS, and 57%
      in confirmed severe ARDS at day 2. In both resolved and confirmed ARDS, age, non
      respiratory SOFA score, lower PEEP and P/F ratio, higher peak pressure and
      respiratory rate were each associated with mortality. In confirmed ARDS, pH and
      the presence of immunosuppression or neoplasm were also associated with
      mortality. The increase in area under the receiver operating curve for ARDS
      reclassification on day 2 was marginal. CONCLUSIONS: ARDS, whether resolved or
      confirmed at day 2, has a high mortality rate. ARDS reclassification at day 2 has
      limited predictive value for mortality. The substantial mortality risk in severe
      confirmed ARDS suggests that complex interventions might best be tested in this
      population. TRIAL REGISTRATION: ClinicalTrials.gov NCT02010073.

PMID- 29633017
TI  - Influence of subject presentation on interpretation of body composition change
      after 6 months of self-selected training and diet in athletic males.
AB  - PURPOSE: High precision body composition assessment methods accurately monitor
      physique traits in athletes. The acute impact of subject presentation (ad libitum
      food and fluid intake plus physical activity) on body composition estimation
      using field and laboratory methods has been quantified, but the impact on
      interpretation of longitudinal change is unknown. This study evaluated the impact
      of athlete presentation (standardised versus non-standardised) on interpretation
      of change in physique traits over time. Thirty athletic males (31.2 +/- 7.5
      years; 182.2 +/- 6.5 cm; 91.7 +/- 10.3 kg; 27.6 +/- 2.6 kg/m2) underwent two
      testing sessions on 1 day including surface anthropometry, dual-energy X-ray
      absorptiometry (DXA), bioelectrical impedance spectroscopy (BIS) and air
      displacement plethysmography (via the BOD POD), with combinations of these used
      to establish three-compartment (3C) and four-compartment (4C) models. METHODS:
      Tests were conducted after an overnight fast (BASEam) and ~ 7 h later after ad
      libitum food/fluid and physical activity (BASEpm). This procedure was repeated 6
      months later (POSTam and POSTpm). Magnitude of changes in the mean was assessed
      by standardisation. RESULTS: After 6 months of self-selected training and diet,
      standardised presentation testing (BASEam to POSTam) identified trivial changes
      from the smallest worthwhile effect (SWE) in fat-free mass (FFM) and fat mass
      (FM) for all methods except for BIS (FM) where there was a large change (7.2%)
      from the SWE. Non-standardised follow-up testing (BASEam to POSTpm) showed
      trivial changes from the SWE except for small changes in FFM (BOD POD) of 1.1%,
      and in FM (3C and 4C models) of 6.4 and 3.5%. Large changes from the SWE were
      found in FFM (BIS, 3C and 4C models) of 2.2, 1.8 and 1.8% and in FM (BIS) of
      6.4%. Non-standardised presentation testing (BASEpm to POSTpm) identified trivial
      changes from the SWE in FFM except for BIS which was small (1.1%). A moderate
      change from the SWE was found for BOD POD (3.3%) and large for BIS (9.4%) in FM
      estimations. CONCLUSIONS: Changes in body composition utilising non-standardised
      presentation were more substantial and often in the opposite direction to those
      identified using standardised presentation, causing misinterpretation of change
      in physique traits. Standardised presentation prior to body composition
      assessment for athletic populations should be advocated to enhance interpretation
      of true change.

PMID- 29633019
TI  - Quality control and improvement of cancer care: what is needed? 4th European
      Roundtable Meeting (ERTM) May 5th, 2017, Berlin, Germany.
AB  - PURPOSE: National Cancer Control Plans (NCCPs) often describe structural
      requirements for high quality cancer care. During the fourth European Roundtable
      Meeting (ERTM) participants shared learnings from their own national setting to
      formulate best practice in optimizing communication strategies between parties
      involved in clinical cancer registries, cancer centers and guideline groups.
      RESULTS: A decentralized model of data collection close to the patient and
      caregiver enhances timely completion and the quality of the data captured.
      Nevertheless, central coordination is necessary to define datasets, indicators,
      standard settings, education, training and quality control to maintain standards
      across the network. In particular, interaction of parties in cancer care network
      has to be established and maintained on a regular basis. CONCLUSION: After
      establishing the structural requirements of cancer care networks, communication
      between the different components and parties is required to analyze outcome data,
      provide regular reporting to all and develop strategies for continuous
      improvement of quality across the network.

PMID- 29633020
TI  - Biodiesel production from algae grown on food industry wastewater.
AB  - Algae have an ample potential to produce biodiesel from spent wash of food
      industry. In addition, it is cheaper and presents an environment friendly way to
      handle food industry wastewater. This study was conducted to optimize the growth
      of microalgal strains and to assess biodiesel production potential of algae using
      untreated food industry wastewater as a source of nutrients. The food industry
      wastewater was collected and analyzed for its physicochemical characteristics.
      Different dilutions (10, 20, 40, 80, and 100%) of this wastewater were made with
      distilled water, and growth of two microalgal strains (Cladophora sp. and
      Spyrogyra sp.) was recorded. Each type of wastewater was inoculated with
      microalgae, and biomass was harvested after 7 days. The growth of both strains
      was also evaluated at varying temperatures, pH and light periods to optimize the
      algal growth for enhanced biodiesel production. After optimization, biodiesel
      production by Spyrogyra sp. was recorded in real food industry wastewater. The
      algal biomass increased with increasing level of food industry wastewater and was
      at maximum with 100% wastewater. Moreover, statistically similar results were
      found with algal growth on 100% wastewater and also on Bristol's media. The
      Cladophora sp. produced higher biomass than Spyrogyra sp. while growing on food
      industry wastewater. The optimal growth of both microalgal strains was observed
      at temperature 30  degrees C, pH: 8, light 24 h. Cladophora sp. was further
      evaluated for biodiesel production while growing on 100% wastewater and found
      that this strain produced high level of oil and biodiesel. Algae have an ample
      potential to produce biodiesel from spent wash of food industry. In addition, it
      is cheaper and presents an environment friendly way to handle food industry
      wastewater.

PMID- 29633022
TI  - Association between mutant IDHs and tumorigenesis in gliomas.
AB  - To become immortalized, cells need to maintain the telomere length via the
      activation of telomerase or alternative lengthening of telomere. Mutations in
      IDH1/2 are strongly associated with the early stage of gliomagenesis. Previous
      work has shown that the accumulation of 2-HG, which is induced by mutant IDH1/2,
      inhibits alpha-KG-dependent deoxygenase and leads to genome-wide histone and DNA
      methylation alterations. These alterations are believed to contribute to
      tumorigenesis. H-Ras can transform human astrocytes with the inactivation of
      p53/pRb and expression of hTERT; however, mutant IDH1 can also transform cells.
      Moreover, mutant IDH1 can drive the immortalization and transformation of p53
      /pRb-deficient astrocytes by reactivating telomerase and stabilizing telomeres in
      combination with increased histone lysine methylation and c-Myc/Max binding at
      the TERT promoter. It remains unclear whether mutant IDH1/2 acts only as the
      initial driver of gliomagenesis or it maintains transformed cells. Clinical
      studies are being performed to assess the use of mutant IDH1/2 inhibitors for
      treating gliomas.

PMID- 29633021
TI  - Risk Prevention of Spreading Emerging Infectious Diseases Using a
      HybridCrowdsensing Paradigm, Optical Sensors, and Smartphone.
AB  - The risk of spreading diseases within (ad-hoc)crowds and the need to pervasively
      screen asymptomatic individuals to protect the population against emerging
      infectious diseases, request permanentcrowd surveillance., particularly in high
      risk regions. Thecase of Ebola epidemic in West Africa in recent years has shown
      the need for pervasive screening. The trend today in diseases surveillance is
      consisting of epidemiological data collection about emerging infectious diseases
      using social media, wearable sensors systems, or mobile applications and data
      analysis. This approach presents various limitations. This paper proposes a novel
      approach for diseases monitoring and risk prevention of spreading infectious
      diseases. The proposed approach, aiming at overcoming the limitation of existing
      disease surveillance approaches, combines the hybrid crowdsensing paradigm with
      sensing individuals' bio-signals using optical sensors for monitoring any risks
      of spreading emerging infectious diseases in any (ad-hoc) crowds. A proof-of
      concept has been performed using a drone armed with a cat s60 smartphone
      featuring a Forward Looking Infra-Red (FLIR) camera. According to the results of
      the conducted experiment, the concept has the potential to improve the
      conventional epidemiological data collection. The measurement is reliable, and
      the recorded data are valid. The measurement error rates are about 8%.

PMID- 29633023
TI  - Cortical processing of speech in individuals with auditory neuropathy spectrum
      disorder.
AB  - OBJECTIVE: Auditory neuropathy spectrum disorder (ANSD) is a condition where
      cochlear amplification function (involving outer hair cells) is normal but neural
      conduction in the auditory pathway is disordered. This study was done to
      investigate the cortical representation of speech in individuals with ANSD and to
      compare it with the individuals with normal hearing. DESIGN: Forty-five
      participants including 21 individuals with ANSD and 24 individuals with normal
      hearing were considered for the study. Individuals with ANSD had hearing
      thresholds ranging from normal hearing to moderate hearing loss. Auditory
      cortical evoked potentials-through odd ball paradigm-were recorded using 64
      electrodes placed on the scalp for /ba/-/da/ stimulus. Onset cortical responses
      were also recorded in repetitive paradigm using /da/ stimuli. Sensitivity and
      reaction time required to identify the oddball stimuli were also obtained.
      RESULT: Behavioural results indicated that individuals in ANSD group had
      significantly lower sensitivity and longer reaction times compared to individuals
      with normal hearing sensitivity. Reliable P300 could be elicited in both the
      groups. However, a significant difference in scalp topographies was observed
      between the two groups in both repetitive and oddball paradigms. Source
      localization using local auto regressive analyses revealed that activations were
      more diffuses in individuals with ANSD when compared to individuals with normal
      hearing sensitivity. CONCLUSION: Results indicated that the brain networks and
      regions activated in individuals with ANSD during detection and discrimination of
      speech sounds are different from normal hearing individuals. In general, normal
      hearing individuals showed more focused activations while in individuals with
      ANSD activations were diffused.

PMID- 29633024
TI  - FDG-PET/CT and diffusion-weighted imaging for resected lung cancer: correlation
      of maximum standardized uptake value and apparent diffusion coefficient value
      with prognostic factors.
AB  - Diffusion-weighted magnetic resonance imaging (DWI) is useful for detecting
      malignant tumors and the assessment of lymph nodes, as FDG-PET/CT is. But it is
      not clear how DWI influences the prognosis of lung cancer patients. The focus of
      this study is to evaluate the correlations between maximum standardized uptake
      value (SUVmax) of FDG-PET/CT and apparent diffusion coefficient (ADC) value of
      DWI with known prognostic factors in resected lung cancer. A total of 227
      patients with resected lung cancers were enrolled in this study. FEG-PET/CT and
      DWI were performed in each patient before surgery. There were 168 patients with
      adenocarcinoma, 44 patients with squamous cell carcinoma, and 15 patients with
      other cell types. SUVmax was a factor that was correlated to T factor, N factor,
      or cell differentiation. ADC of lung cancer was a factor that was not correlated
      to T factor, or N factor. There was a significantly weak inverse relationship
      between SUVmax and ADC (Correlation coefficient r = - 0.227). In analysis of
      survival, there were significant differences between the categories of sex, age,
      pT factor, pN factor, cell differentiation, cell type, and SUVmax. Univariate
      analysis revealed that SUVmax, pN factor, age, cell differentiation, cell type,
      sex, and pT factor were significant factors. Multivariate analysis revealed that
      SUVmax and pN factor were independent significant prognostic factors. SUVmax was
      a significant prognostic factor that is correlated to T factor, N factor, or cell
      differentiation, but ADC was not. SUVmax may be more useful for predicting the
      prognosis of lung cancer than ADC values.

PMID- 29633025
TI  - Effect of cervical priming with misoprostol on cervical entry in women undergoing
      vaginoscopic hysteroscopy for evaluation of abnormal uterine bleeding: a
      randomized controlled trial.
AB  - OBJECTIVE: To study the effect of cervical priming with misoprostol on cervical
      entry in women undergoing diagnostic hysteroscopy for evaluation of abnormal
      uterine bleeding. METHODS: Randomized controlled trial conducted in teaching
      hospital and tertiary referral center on 122 women requiring diagnostic
      hysteroscopy for evaluation of abnormal uterine bleeding. Women were randomized
      into two equal groups (n = 122). Study group received 200-MUg vaginal
      misoprostol, 3 h prior to vaginoscopic hysteroscopy. No drug was used in control
      group. No analgesia or anesthesia was used in either group. Outcome measure
      included (i) ease of cervical entry (Likert scale), and (ii) pain scoring (Visual
      Analog Scale) and procedural entry time. RESULTS: Forty-six (75.41%) patients in
      the study group and 17 (27.87%) in control group had easy or very easy entry
      (Likert scale-4 and 5) (p < 0.001). Median pain scoring by VAS and the median
      procedural entry time was significantly lower in the study group compared to the
      control group (p < 0.001). CONCLUSION: Use of 200-MUg vaginal misoprostol,
      administered vaginally 3 h before diagnostic vaginoscopic hysteroscopy, was found
      to be simple and effective method of cervical priming in facilitating cervical
      entry with minimal side effects. Clinical Trial registry of India (CTRI):
      (CTRI/2015/04/005666) (website: http://ctri.nic.in ).

PMID- 29633026
TI  - Correction to: Escherichia coli persistence kinetics in dairy manure at moderate,
      mesophilic, and thermophilic temperatures under aerobic and anaerobic
      environments.
AB  - Escherichia coli persistence kinetics in dairy manure at moderate, mesophilic,
      and thermophilic temperatures.

PMID- 29633028
TI  - Star paper session.

PMID- 29633029
TI  - Free Papers.

PMID- 29633031
TI  - Evaluation of new lesions and symptoms after gamma knife radiosurgery for brain
      metastases: a retrospective cohort study.
AB  - BACKGROUND: Symptomatic new lesions that appear after gamma knife radiosurgery
      (GKRS) for brain metastases have not been thoroughly described. METHODS: Among
      238 patients who underwent a single session of GKRS without whole-brain
      radiotherapy or surgery for brain metastases between 2009 and 2014, a total of
      165 (69.3%) patients underwent follow-up magnetic resonance imaging (MRI). Their
      electrical health records were reviewed retrospectively. The median age was 68
      years, and 62.4% patients were men. The median number of brain metastases was 2.
      The most frequent primary organ site was the lung (71.5%). Then, we evaluated
      predictors for the symptoms of new lesions. RESULTS: New lesions and
      leptomeningeal dissemination were observed in 101 (61.2%) and 23 (14.2%)
      patients, respectively. The median number of new lesions was 2; moreover, 20 of
      101 patients (19.8%) with new lesions had tumours with the largest diameters of >
      1 cm. Among 101 patients with new lesions, 13 were symptomatic (12.9%). Patients
      with larger new lesions (> 1 cm of the largest diameter) experienced symptoms
      more frequently (odds ratio 7.6, P < 0.01). Symptoms resolved after salvage GKRS
      in seven of 11 patients who abided by the recommended follow-up MRI schedule. No
      significant risk factors were found for symptoms of new lesions. CONCLUSIONS: The
      incidence of symptomatic new lesions that appeared after GKRS was low, and more
      than half of the patients showed improvements in their symptoms after salvage
      GKRS. However, careful MRI-based assessments and salvage GKRS are critical for
      the quality of life.

PMID- 29633032
TI  - An assessment of nutrients and sedimentation in the St. Thomas East End Reserves,
      US Virgin Islands.
AB  - Nutrients and sedimentation were monitored for approximately 2 years at six sites
      in the St. Thomas East End Reserves (STEER), St. Thomas, USVI, as part of a NOAA
      project to develop an integrated environmental assessment. Concentrations of
      ammonium (NH4+) and dissolved inorganic nitrogen (DIN) were higher in Mangrove
      Lagoon and Benner Bay in the western portion of STEER than in the other sites
      further east (i.e., Cowpet Bay, Rotto Cay, St. James, and Little St. James).
      There was no correlation between rainfall and nutrient concentrations. Using a
      set of suggested nutrient thresholds that have been developed to indicate the
      potential for the overgrowth of algae on reefs, approximately 60% of the samples
      collected in STEER were above the threshold for orthophosphate (HPO4=), while 55%
      of samples were above the DIN threshold. Benner Bay had the highest sedimentation
      rate of any site monitored in STEER, including Mangrove Lagoon. There was also an
      east to west and a north to south gradient in sedimentation, indicative of higher
      sedimentation rates in the western, more populated areas surrounding STEER, and
      sites closer to the shore of the main island of St. Thomas. Although none of the
      sites had a mean or average sedimentation rate above a suggested sedimentation
      threshold, the mean sedimentation rate in Benner Bay was just below the
      threshold.

PMID- 29633033
TI  - [Antibiotic consumption and antimicrobial resistance in human and veterinary
      medicine : An overview of established national surveillance systems in Germany].
AB  - The German Antimicrobial Resistance Strategy (DART) assigns a key role in
      combatting and reducing the further development and spread of antimicrobial
      resistance to the setup and development of instruments for the monitoring and
      surveillance of antimicrobial resistance and antibiotic consumption. The strategy
      follows the One Health approach, which targets human and veterinary medicine
      alike. An ongoing collection of appropriate data on antimicrobial resistance and
      antibiotic consumption and its distribution in time and space, will provide the
      basis for the identification of problems, the deduction of interventions, and
      finally the evaluation of their effectiveness. This article presents an overview
      of established surveillance systems in human and veterinary medicine with a
      national scope, including those that enable Germany to meet its own legal
      commitments as well as those within European and international action plans.

PMID- 29633034
TI  - [Rational prescription of antibiotics in human medicine].
AB  - Rational prescription of antibiotics has become a priority in undergraduate and
      continued professional medical education and in quality management systems. Areas
      for optimization have been identified, above all, in critically establishing the
      indication for therapy, in increasing targeted therapy, and shortening treatment
      duration, and affect both outpatient and inpatient settings. They are partly
      related to deficiencies in clinical research, but aberrations in the development
      of the postgraduate training system, in the infrastructure, and in the
      reimbursement system of the various healthcare sectors in Germany contribute to
      problems in these areas. "Antibiotic stewardship" (ABS) programmes at different
      levels are capable of efficiently combining interventions to improve the quality
      of prescription. Progress has been made and experience gained in the professional
      training of physicians and pharmacists in antibiotic prescribing and with the
      hospital-wide establishment of ABS teams and specialist infectious disease
      consultation services. Close interaction and collaboration with diagnostic
      microbiology services are important and greatly enhance the impact of ABS
      programmes on the quality of prescription. Political support and investment are
      required for this new infrastructures to be sustainable and to further develop it
      for the cross-section between inpatients and outpatients, and for the outpatient
      setting.

PMID- 29633035
TI  - [Erratum to: Prevalence of dementia of insured persons with and without German
      citizenship : A study based on statutory health insurance data].

PMID- 29633036
TI  - [Antibiotic resistance : A challenge for society].
AB  - Without doubt, drug resistance is now one of the greatest health threats of our
      time. Not even 100 years after the discovery of the first antibiotics that saved
      human lives, we find ourselves threatened by the thought of a post-antibiotic
      era. Currently it is estimated that around 700,000 people die annually as a
      consequence of drug-resistant infections. Antibiotic resistance is a natural
      phenomenon with bacteria having devised several ways of combating the antibiotic
      attack. Rather than being a spontaneous event, resistance becomes an integral
      part of the microbe's genetic make-up, spreading further between and across
      species. However, the misuse and overuse of antibiotics over the years has in
      fact allowed for resistant bacteria to thrive, while slowly wiping out sensitive
      bacteria. Spreading awareness and proper information in the community about the
      risks and consequences of a rapidly developing antibiotic resistance is essential
      in tackling this global problem. In working together as an entire community, we
      can find long-lasting solutions. The One Health concept includes human and
      veterinary medical sectors, the environmental sector, as well as various decision
      making bodies that include individual action as well as national and
      international policymakers. The role of stakeholders like pharmaceutical
      companies and agriculturists must be given importance, too, thinking all the
      while in a global context. Only this way will we find solutions for sustainable
      healthcare and together help slow down the process of antibiotic resistance.

PMID- 29633037
TI  - [The environment as a reservoir for antimicrobial resistance : A growing problem
      for public health?]
AB  - Antimicrobial resistance (AMR) is a threat to public and animal health on the
      global scale. The origin of the genes associated with resistance has long been
      unknown. Recently, there is a growing body of evidence demonstrating that
      environmental bacteria are resistant to a multitude of antibiotic substances and
      that this environmental reservoir of AMR is still growing. The analysis of the
      genomes of bacterial pathogens indicates that they have acquired their resistance
      profiles by incorporating different genetic elements through horizontal gene
      transfer. The ancestors of pathogenic bacteria, as well as the origin of
      resistance determinants, lay most likely in the environmental microbiota. Indeed,
      there is some evidence that at least some clinically relevant resistance genes
      have originated in environmental bacterial species. Thus, feasible measures are
      required to reduce the risks posed by AMR genes and resistant bacteria that occur
      in the environment. It has been shown that a concurrence of factors, such as high
      concentrations of antibiotics or heavy metals used as biocides and high bacterial
      densities, promote development and spread of antimicrobial resistance. For this
      purpose, it is essential to restrict the use of antibiotics for the treatment of
      livestock and humans to medical necessity, as well as to reduce the application
      of biocides and heavy metals in animal husbandry. Moreover, it is important to
      further develop sanitary measures at the interface between the environment and
      clinical settings or livestock farming.

PMID- 29633038
TI  - [Effective management of an outbreak with multiresistent Klebsiella pneumoniae in
      a neurorehabilitation unit].
AB  - BACKGROUND: In addition to acute care hospitals, rehabilitation centres are
      increasingly confronted with multi-resistant pathogens. Long durations of stay
      and intensive treatments impose special hygienic challenges. MATERIAL AND
      METHODS: We investigated an extended spectrum beta-lactamase-Klebsiella
      pneumoniae (ESBL-K. pneumoniae) outbreak in a neurorehabilitation centre. We
      defined confirmed cases as patients who stayed in the centre during the outbreak
      period and from whom ESBL-K. pneumoniae was isolated with the outbreak sequence
      type. Probable cases had an epidemiological link to at least one confirmed case
      but no isolate for typing. Next generation sequencing (NGS) was performed on 53
      isolates from patients. Environmental sampling was performed. Systematic
      microbiological screening was implemented and ESBL-K. pneumoniae-positive
      patients were cohorted in a designated ward. RESULTS: We identified 30 confirmed
      and 6 probable cases. NGS revealed three genetic clusters: Cluster 1 - the
      outbreak cluster - with isolates of 30 cases (sequence type ST15), Cluster 2 with
      7 patients (ST405) and Cluster 3 with 8 patients (ST414). In two patients, the
      outbreak strain developed further antibiotic resistance, one with colistin
      resistance and the other carbapenem resistance. The outbreak ceased after strict
      isolation measures. DISCUSSION: Epidemiology and NGS results paired with the
      effectiveness of cohorting suggest that transmission occurred mainly from person
      to person in this outbreak. There was an apparent association of the probability
      to acquire ESBL-K. pneumoniae and treatment intensity, whereas infection rate was
      related to morbidity. The identification of the outbreak clone and additional
      clusters plus the development of additional antibiotic resistance shows the
      relevance of NGS and highlights the need for timely and efficient outbreak
      management.

PMID- 29633041
TI  - Long-term survival with extended lateral lymphadenectomy for lateral lymph node
      recurrence after laparoscopic abdominoperineal resection for rectal adenosquamous
      carcinoma: a case report.
AB  - The patient was a 54-year-old female who presented with the chief complaint of
      melena. Lower gastrointestinal endoscopy detected a type 1 tumor extending from
      the anal canal to the rectum. CT did not detect any distant metastasis. Proximal
      D3 lymphadenectomy with laparoscopic abdominoperineal resection was performed for
      stage IA rectal cancer. In the histopathological examination, the tumor was
      identified as stage IIIa adenosquamous carcinoma. Although the patient underwent
      postoperative adjuvant chemotherapy with S-1, a recurrent left lateral lymph node
      tumor was detected on CT and PET 12 months later. The patient underwent the
      treatment with mFOLFOX + bevacizumab for 6 months. However, the tumor continued
      to progress, and therefore, extended lateral lymphadenectomy was performed 21
      months after the first surgery. The patient did not undergo postoperative
      adjuvant therapy and is alive without recurrence 90 months after the first
      surgery and 70 months after the reoperation. Adenosquamous carcinoma of the
      rectum is a rare histological type of colorectal cancer for which there is no
      effective treatment besides surgical resection, and its prognosis is known to be
      worse than that of adenocarcinoma. Since there has been no report of long-term
      survival after extended lateral lymphadenectomy for recurrent lateral lymph node
      tumors following surgery for adenosquamous carcinoma of the rectum, herein, we
      report the case with a review of the literature.

PMID- 29633040
TI  - Thai Hom Mali Rice: Origin and Breeding for Subsistence Rainfed Lowland Rice
      System.
AB  - The world-renowned Thai Hom Mali Rice has been the most important aromatic rice
      originating in Thailand. The aromatic variety was collected from Chachoengsao, a
      central province, and after pure-line selection, it was officially named as Khao
      Dawk Mali 105, (KDML105). Because of its superb fragrance and cooking quality,
      KDML105 has been a model variety for studying genes controlling grain quality and
      aroma. The aromatic gene was cloned in KDML105, as an amino aldehyde
      dehydrogenase (AMADH) or better known as BADH2 located on chromosome 8. Later on,
      all other aromatic rice genes were discovered as allelic to the AMADH. As a
      selection of local landrace variety found in rainfed areas, the Thai Jasmine rice
      showed adaptive advantages over improved irrigated rice in less fertile lowland
      rainfed conditions. Because KDML105 was susceptible to most diseases and insect
      pests, marker-assisted backcross selection (MABC) was used for the genetic
      improvement since 2000. After nearly 17 years of MABC for integrating new traits
      into KDML105, a new generation of KDML105, designated HM84, was developed which
      maintains the cooking quality and fragrance, and has gained advantages during
      flash flooding, disease, and insect outbreak.

PMID- 29633039
TI  - Molecular composition of the human primary visual cortex profiled by multimodal
      mass spectrometry imaging.
AB  - The primary visual cortex (area V1) is an extensively studied part of the
      cerebral cortex with well-characterized connectivity, cellular and molecular
      architecture and functions (for recent reviews see Amunts and Zilles, Neuron
      88:1086-1107, 2015; Casagrande and Xu, Parallel visual pathways: a comparative
      perspective. The visual neurosciences, MIT Press, Cambridge, pp 494-506, 2004).
      In humans, V1 is defined by heavily myelinated fibers arriving from the radiatio
      optica that form the Gennari stripe in cortical layer IV, which is further
      subdivided into laminae IVa, IVb, IVcalpha and IVcbeta. Due to this unique
      laminar pattern, V1 represents an excellent region to test whether multimodal
      mass spectrometric imaging could reveal novel biomolecular markers for a
      functionally relevant parcellation of the human cerebral cortex. Here we analyzed
      histological sections of three post-mortem brains with matrix-assisted laser
      desorption/ionization mass spectrometry imaging and laser ablation inductively
      coupled plasma mass spectrometry imaging to investigate the distribution of
      lipids, proteins and metals in human V1. We identified 71 peptides of 13
      different proteins by in situ tandem mass spectrometry, of which 5 proteins show
      a differential laminar distribution pattern revealing the border between V1 and
      V2. High-accuracy mass measurements identified 123 lipid species, including
      glycerolipids, glycerophospholipids and sphingolipids, of which at least 20
      showed differential distribution within V1 and V2. Specific lipids labeled not
      only myelinated layer IVb, but also IVa and especially IVc in a layer-specific
      manner, but also and clearly separated V1 from V2. Elemental imaging further
      showed a specific accumulation of copper in layer IV. In conclusion, multimodal
      mass spectrometry imaging identified novel biomolecular and elemental markers
      with specific laminar and inter-areal differences. We conclude that mass
      spectrometry imaging provides a promising new approach toward multimodal,
      molecule-based cortical parcellation.

PMID- 29633042
TI  - Cefazolin-Related Acute Interstitial Nephritis with Associated Nephrotic-Range
      Proteinuria: A Case Report.
AB  - A 67-year-old male with history of well controlled type 2 diabetes mellitus and
      hypertension developed acute interstitial nephritis (AIN) with nephrotic-range
      proteinuria during treatment with cefazolin for methicillin-sensitive
      Staphylococcus aureus and Group B Streptococcus (GBS) bacteremia. The patient
      received intravenous cefazolin 2 g every 8 h for 4 weeks prior to presentation to
      the emergency department with abdominal distension, nausea, and vomiting.
      Investigations revealed a serum ascites albumin gradient of 1.0 with total
      protein of 1.8 g/dL suggestive of nephrotic syndrome, which was confirmed with a
      spot urine protein/creatinine ratio that estimated 7.95 g of protein per day.
      Serum creatinine was elevated compared with baseline. Urine studies showed
      sterile pyuria with 3+ protein and eosinophiluria. The patient was diagnosed with
      AIN with nephrotic-range proteinuria associated with cefazolin use. Cefazolin was
      discontinued and, within a couple of days, the patient's creatinine stabilized.
      He was discharged with prednisone 60 mg once a day for 10 days with a taper over
      2 weeks for his AIN. The patient's creatinine and proteinuria slowly decreased
      over the next couple of weeks, however, did not recover to baseline. A Naranjo
      assessment score of 6 was obtained, indicating a probable relationship between
      the patient's AIN with nephrotic-range proteinuria and his use of cefazolin.

PMID- 29633043
TI  - Ultrasonic versus monopolar energy-based surgical devices in terms of surgical
      smoke and lateral thermal damage (ULMOST): a randomized controlled trial.
AB  - BACKGROUND: The purpose of this study was to compare the degree of surgical smoke
      or vapor and lateral thermal damage caused by two different energy-based surgical
      devices (ESDs) used in colpotomy during total laparoscopic hysterectomy. METHODS:
      Patients undergoing laparoscopic hysterectomy were randomly assigned to an
      ultrasonic ESD group (n = 20) or monopolar ESD group (n = 20). Colpotomy was
      performed using the assigned ESD. The degree of surgical smoke or vapor
      obstructing the laparoscopic view was assessed by two independent reviewers using
      a 5-point Likert scale, in which a higher score indicates worse visibility. The
      degree of the lateral thermal damage was measured as the width from the point of
      instrument application to the margins of the unchanged nearby tissue using a
      light microscope. RESULTS: The baseline characteristics did not statistically
      differ between the two groups. The degree of surgical smoke or vapor obstructing
      vision was 1.2 +/- 0.8 points in the ultrasonic group and 3.9 +/- 0.7 points in
      the monopolar groups (p < 0.001). The lateral thermal damage was significantly
      increased in the monopolar group compared to in the ultrasound group (1500 um
      [1200-2500 um] vs. 950 um [650-1725 um], p = 0.037). CONCLUSION: Ultrasonic ESD
      had better laparoscopic visibility and caused less lateral thermal damage during
      colpotomy compared to monopolar device.

PMID- 29633044
TI  - Cystic gastric metastasis from pancreatic cancer.
AB  - Gastrointestinal tract metastasis from pancreatic cancer is quite rare. We
      present the case of a 58-year-old male patient who underwent distal
      pancreatectomy for pancreatic body cancer 5 years prior. Four years after the
      initial operation, a 15-mm cystic submucosal tumor was found in the antrum of the
      stomach. Because the tumor had grown to 25 mm and the level of carcinoembryonic
      antigen in the cystic fluid derived by ultrasound-guided fine-needle aspiration
      biopsy was high, partial resection of the stomach was performed 5 years after the
      distal pancreatectomy. Pathological diagnosis was gastric metastasis of
      pancreatic cancer. The patient has been alive without recurrence for 13 months
      after the resection of the cystic tumor. We are not aware of any similar cases of
      cystic gastric metastasis from pancreatic cancer published in the English
      literature.

PMID- 29633045
TI  - Stature estimation based on femoral measurements in the modern Japanese
      population: a cadaveric study using multidetector computed tomography.
AB  - We aimed to reproduce the anthropometrical measurement of femoral dimensions
      using multi-planar reconstruction computed tomography (CT), assess the
      correlation between stature and femoral measurements obtained by this approach,
      and establish a regression equation for estimating stature in the modern Japanese
      population. We used data regarding 224 cadavers (116 males, 108 females) that
      were subjected to postmortem CT and subsequent forensic autopsy at our department
      between October 2009 and July 2016. To simulate the placement of the femur on the
      osteometric board using reconstructed CT images, we defined a virtual horizontal
      plane (VHP) based on the three most dorsal points of the femur (lateral condyle,
      medial condyle, and greater trochanter). Five femoral measurements including the
      maximum femoral length (MFL) were obtained. The correlations between stature and
      each femoral measurement were expressed in terms of the coefficient of
      determination (R2). On regression analysis, MFL provided the lowest value for the
      standard error of the estimation (SEE); the SEE values in all subjects, males,
      and females, respectively, were 3.783 cm (R2 = 0.832), 3.850 cm (R2 = 0.653), and
      3.340 cm (R2 = 0.760) for MFL on the left side and 3.747 cm (R2 = 0.835), 3.847
      cm (R2 = 0.650), and 3.290 cm (R2 = 0.687) for MFL on the right side. Multiple
      regression equations using MFL and femoral epicondylar breadth were slightly
      superior to simple regression equations in males and in all subjects (SEE = 3.44
      3.55 cm), whereas no effective equation could be obtained in females. To our
      knowledge, this is the first multiple regression equation for stature estimation
      using only femoral measurements.

PMID- 29633046
TI  - Assessment of glucose metabolism and cellular proliferation in multiple myeloma:
      a first report on combined 18F-FDG and 18F-FLT PET/CT imaging.
AB  - BACKGROUND: Despite the significant upgrading in recent years of the role of 18F
      FDG PET/CT in multiple myeloma (MM) diagnostics, there is a still unmet need for
      myeloma-specific radiotracers. 3'-Deoxy-3'-[18F]fluorothymidine (18F-FLT) is the
      most studied cellular proliferation PET agent, considered a potentially new
      myeloma functional imaging tracer. The aim of this pilot study was to evaluate
      18F-FLT PET/CT in imaging of MM patients, in the context of its combined use with
      18F-FDG PET/CT. RESULTS: Eight patients, four suffering from symptomatic MM and
      four suffering from smoldering MM (SMM), were enrolled in the study. All patients
      underwent 18F-FDG PET/CT and 18F-FLT PET/CT imaging by means of static (whole
      body) and dynamic PET/CT of the lower abdomen and pelvis (dPET/CT) in two
      consecutive days. The evaluation of PET/CT studies was based on qualitative
      evaluation, semi-quantitative (SUV) calculation, and quantitative analysis based
      on two-tissue compartment modeling. 18F-FDG PET/CT demonstrated focal, 18F-FDG
      avid, MM-indicative bone marrow lesions in five patients. In contrary, 18F-FLT
      PET/CT showed focal, 18F-FLT avid, myeloma-indicative lesions in only two
      patients. In total, 48 18F-FDG avid, focal, MM-indicative lesions were detected
      with 18F-FDG PET/CT, while 17 18F-FLT avid, focal, MM-indicative lesions were
      detected with 18F-FLT PET/CT. The number of myeloma-indicative lesions was
      significantly higher for 18F-FDG PET/CT than for 18F-FLT PET/CT. A common finding
      was a mismatch of focally increased 18F-FDG uptake and reduced 18F-FLT uptake
      (lower than the surrounding bone marrow). Moreover, 18F-FLT PET/CT was
      characterized by high background activity in the bone marrow compartment, further
      complicating the evaluation of bone marrow lesions. Semi-quantitative evaluation
      revealed that both SUVmean and SUVmax were significantly higher for 18F-FLT than
      for 18F-FDG in both MM lesions and reference tissue. SUV values were higher in MM
      lesions than in reference bone marrow for both tracers. CONCLUSIONS: Despite the
      limited number of patients analyzed in this pilot study, the first results of the
      trial indicate that 18F-FLT does not seem suitable as a single tracer in MM
      diagnostics. Further studies with a larger patient population are warranted to
      generalize the herein presented results.

PMID- 29633048
TI  - Old Drugs for New Indications in Cardiovascular Medicine.
AB  - Inflammation participates in the initiation and progression of atherosclerotic
      cardiovascular disease, and it is a critical inciting factor leading to acute
      ischemic events. Evidence has shown that certain anti-inflammatory medications
      used to treat non-atherosclerotic inflammatory diseases reduce cardiovascular
      events. This article reviews evidence that commonly used anti-inflammatory
      therapies (colchicine, allopurinol, methotrexate), reduce cardiovascular events.
      We discuss potential mechanisms of action, efficacy, and safety of these
      therapies and propose a clinical trials design to investigate their efficacy.

PMID- 29633047
TI  - KRDS: a web server for evaluating drug resistance mutations in kinases by
      molecular docking.
AB  - Kinases are major targets of anti-cancer therapies owing to their importance in
      signaling processes that regulate cell growth and proliferation. However, drug
      resistance has emerged as a major obstacle to cancer therapy. Resistance to drugs
      has various underlying mechanisms, including the acquisition of mutations at drug
      binding sites and the resulting reduction in drug binding affinity. Therefore,
      the identification of mutations that are relevant to drug resistance may be
      useful to overcome this issue. We hypothesized that these mutations can be
      identified by combining recent advances in computational methods for protein
      structure modeling and ligand docking simulation. Hence, we developed a web-based
      tool named the Kinase Resistance Docking System (KRDS) that enables the
      assessment of the effects of mutations on kinase-ligand interactions. KRDS
      receives a list of mutations in kinases, generates structural models of the
      mutants, performs docking simulations, and reports the results to users. The
      changes in docking scores and docking conformations can be analyzed to infer the
      effects of mutations on drug binding and drug resistance. We expect our tool to
      improve our understanding of drug binding mechanisms and facilitate the
      development of effective new drugs to overcome resistance related to kinases; it
      may be particularly useful for biomedical researchers who are not familiar with
      computational environments. Our tool is available at
      http://bcbl.kaist.ac.kr/KRDS/ .

PMID- 29633050
TI  - Dispatches from the land of the morning calm: special issue papers from the 18th
      International Symposium on the Biology of Actinomycetes.

PMID- 29633049
TI  - Cortical Processing Related to Intensity of a Modulated Noise Stimulus-a
      Functional Near-Infrared Study.
AB  - Sound intensity is a key feature of auditory signals. A profound understanding of
      cortical processing of this feature is therefore highly desirable. This study
      investigates whether cortical functional near-infrared spectroscopy (fNIRS)
      signals reflect sound intensity changes and where on the brain cortex maximal
      intensity-dependent activations are located. The fNIRS technique is particularly
      suitable for this kind of hearing study, as it runs silently. Twenty-three normal
      hearing subjects were included and actively participated in a counterbalanced
      block design task. Four intensity levels of a modulated noise stimulus with long
      term spectrum and modulation characteristics similar to speech were applied,
      evenly spaced from 15 to 90 dB SPL. Signals from auditory processing cortical
      fields were derived from a montage of 16 optodes on each side of the head.
      Results showed that fNIRS responses originating from auditory processing areas
      are highly dependent on sound intensity level: higher stimulation levels led to
      higher concentration changes. Caudal and rostral channels showed different
      waveform morphologies, reflecting specific cortical signal processing of the
      stimulus. Channels overlying the supramarginal and caudal superior temporal gyrus
      evoked a phasic response, whereas channels over Broca's area showed a broad tonic
      pattern. This data set can serve as a foundation for future auditory fNIRS
      research to develop the technique as a hearing assessment tool in the normal
      hearing and hearing-impaired populations.

PMID- 29633051
TI  - Computational Fragment-Based Drug Design: Current Trends, Strategies, and
      Applications.
AB  - Fragment-based drug design (FBDD) has become an effective methodology for drug
      development for decades. Successful applications of this strategy brought both
      opportunities and challenges to the field of Pharmaceutical Science. Recent
      progress in the computational fragment-based drug design provide an additional
      approach for future research in a time- and labor-efficient manner. Combining
      multiple in silico methodologies, computational FBDD possesses flexibilities on
      fragment library selection, protein model generation, and fragments/compounds
      docking mode prediction. These characteristics provide computational FBDD
      superiority in designing novel and potential compounds for a certain target. The
      purpose of this review is to discuss the latest advances, ranging from commonly
      used strategies to novel concepts and technologies in computational fragment
      based drug design. Particularly, in this review, specifications and advantages
      are compared between experimental and computational FBDD, and additionally,
      limitations and future prospective are discussed and emphasized.

PMID- 29633052
TI  - A Systematic Review of Three-Dimensional Printing in Liver Disease.
AB  - The purpose of this review is to analyse current literature related to the
      clinical applications of 3D printed models in liver disease. A search of the
      literature was conducted to source studies from databases with the aim of
      determining the applications and feasibility of 3D printed models in liver
      disease. 3D printed model accuracy and costs associated with 3D printing, the
      ability to replicate anatomical structures and delineate important
      characteristics of hepatic tumours, and the potential for 3D printed liver models
      to guide surgical planning are analysed. Nineteen studies met the selection
      criteria for inclusion in the analysis. Seventeen of them were case reports and
      two were original studies. Quantitative assessment measuring the accuracy of 3D
      printed liver models was analysed in five studies with mean difference between 3D
      printed models and original source images ranging from 0.2 to 20%. Fifteen
      studies provided qualitative assessment with results showing the usefulness of 3D
      printed models when used as clinical tools in preoperative planning, simulation
      of surgical or interventional procedures, medical education, and training. The
      cost and time associated with 3D printed liver model production was reported in
      11 studies, with costs ranging from US$13 to US$2000, duration of production up
      to 100 h. This systematic review shows that 3D printed liver models demonstrate
      hepatic anatomy and tumours with high accuracy. The models can assist with
      preoperative planning and may be used in the simulation of surgical procedures
      for the treatment of malignant hepatic tumours.

PMID- 29633054
TI  - Toxicity assessment of copper by electrochemically active bacteria in wastewater.
AB  - A bioelectrochemical sensor (BES) was constructed for toxicity assessment of
      copper in contaminated domestic sewage. Electrochemically active bacteria (EAB),
      whose growth was supported by the bioenergy generated from an in situ
      metallurgical process, functioned as the sensing elements. The external
      resistance of metallurgical BES was optimized based on linear sweep voltammetry
      analysis. The stabilized BES was utilized to monitor the copper toxicity in real
      wastewater. During the less than 1-h sensing period, copper concentration ranging
      from 1 to 5 mg L-1 could be detected. A power output of around 100 Wh (kg Cu)-1
      and metallic copper resource were obtained simultaneously. This study
      demonstrated that the highly active EAB species enriched in metallurgical BES
      could be a promising candidate for rapid and reliable evaluation of copper
      toxicity in real domestic wastewater.

PMID- 29633053
TI  - Total iron-binding capacity is a novel prognostic marker after curative
      gastrectomy for gastric cancer.
AB  - BACKGROUND: Patients with gastric cancer (GC) are affected by changes in iron
      status. Before surgery, GC patients are likely to have iron-deficiency anemia;
      and after gastrectomy, patients suffer from low nutritional status and low iron.
      This study investigated preoperative iron status associated with prognosis after
      curative gastrectomy for gastric cancer. METHODS: We evaluated preoperative serum
      hemoglobin (Hgb), Fe and total iron-binding capacity (TIBC) in 298 patients who
      underwent curative gastrectomy for GC without preoperative chemotherapy, and
      analyzed these factors' associations with prognosis after surgery. RESULTS: Of
      the 298 patients, 129 (43.2%) had low Hgb levels, and 33 (11.1%) had low TIBC (<
      260 ug/dl) that was not associated with Hgb or Fe level. Patients with low TIBC
      were significantly associated with older age (>= 65 years old; P = 0.0085), low
      albumin (< 3.9 g/dl; P = 0.0388) and high CRP (>= 0.15 mg/dl; P = 0.0018) in
      multivariate analysis. Low Fe (< 60 ug/dl) was not associated with disease-free
      survival (DFS) or overall survival (OS); however, low Fe was associated with
      longer cancer-specific survival in Stage III GC patients (P = 0.0333). Both low
      Hgb and low TIBC were significantly associated with shorter DFS (Hgb: P = 0.0433;
      TIBC: P < 0.0001) and shorter OS (Hgb: P = 0.0352; TIBC: P < 0.0001). Low TIBC
      were significantly associated with shorter DFS (HR 2.167, 95% CI 1.231-3.639, P =
      0.0086) and shorter OS (HR 2.065, 95% CI 1.144-3.570, P = 0.0173) in multivariate
      Cox hazard regression analysis. CONCLUSIONS: Preoperative serum TIBC level of GC
      patients who undergo curative gastrectomy is a novel prognostic marker in
      univariate and multivariate analyses.

PMID- 29633055
TI  - Clinical and biological roles of Kelch-like family member 7 in breast cancer: a
      marker of poor prognosis.
AB  - BACKGROUND: The functions of many proteins are tightly regulated with a complex
      array of cellular functions including ubiquitination. In cancer cells, aberrant
      ubiquitination may promote the activity of oncogenic pathways with subsequent
      tumour progression. Kelch-like family member 7 (KLHL7) is involved in the
      regulation of ubiquitination and may play a role in breast cancer (BC). Present
      study aims to evaluate the biological and clinical usefulness of KLHL7 in BC
      utilising large well-characterised cohorts with long-term follow-up. METHODS: The
      relationships between KLHL7 gene copy number alteration (CNA) and mRNA expression
      and clinicopathological variables and clinical outcomes were evaluated in 1980
      patients from the METABRIC BC cohort. Prognostic significance of KLHL7 mRNA was
      validated using the Breast Cancer Gene-Expression Miner v4.0 datasets (n = 5206).
      KLHL7 protein expression was assessed using immunohistochemistry in a large
      annotated series of early-stage BC (n = 917) with long-term follow-up. RESULTS:
      KLHL7 CNA was significantly correlated with its mRNA expression. KLHL7 mRNA
      expression was higher in luminal B and basal-like molecular subtypes and in
      higher grade tumours. Increased KLHL7 protein expression was significantly
      correlated with features of aggressive phenotype including lymphovascular
      invasion, high histological grade, hormonal receptor negativity, high PIK3CA and
      p53 expression. Outcome analysis showed that high KLHL7 expression is an
      independent predictor of shorter survival (p = 0.0011). CONCLUSIONS: KLHL7
      appears to play an important role in BC progression. High KLHL7 protein
      expression identified a subgroup of BC with aggressive behaviour and provided
      independent prognostic information.

PMID- 29633056
TI  - Positional effects on the distributions of ventilation and end-expiratory gas
      volume in the asymmetric chest-a quantitative lung computed tomographic analysis.
AB  - BACKGROUND: Body positioning affects the configuration and dynamic properties of
      the chest wall and therefore may influence decisions made to increase or decrease
      ventilating pressures and tidal volume. We hypothesized that unlike global
      functional residual capacity (FRC), component sector gas volumes and their
      corresponding regional tidal expansions would vary markedly in the setting of
      unilateral pleural effusion (PLEF), owing to shifting distributions of aeration
      and collapse as posture changed. METHODS: Six deeply anesthetized swine underwent
      tracheostomy, thoracostomy, and experimental PLEF with 10 mL/kg of radiopaque
      isotonic fluid randomly instilled into either pleural space. Animals were
      ventilated at VT = 10 mL/kg, frequency = 15 bpm, I/E = 1:2, PEEP = 1 cmH2O, and
      FiO2 = 0.5. Quantitative lung computed tomographic (CT) analysis of regional
      aeration and global FRC measurements by nitrogen wash-in/wash-out technique was
      performed in each of these randomly applied positions: semi-Fowler's (inclined 30
      degrees  from horizontal in the sagittal plane); prone, supine, and lateral
      positions with dependent PLEF and non-dependent PLEF. RESULTS: No significant
      differences in total FRC were observed among the horizontal positions, either at
      baseline (p = 0.9037) or with PLEF (p = 0.58). However, component sector total
      gas volumes in each phase of the tidal cycle were different within all studied
      positions with and without PLEF (p = < .01). Compared to other positions, prone
      and lateral positions with non-dependent PLEF had more homogenous VT
      distributions among quadrants (p = .051). Supine position was associated with
      most dependent collapse and greatest tendency for tidal recruitment (48 vs ~ 22%,
      p = 0.0073). CONCLUSIONS: Changes in body position in the setting of effusion
      caused chest asymmetry markedly affected the internal distributions of gas
      volume, collapse, ventilation, and tidal recruitment, even though global FRC
      measurements provided little indication of these potentially important positional
      changes.

PMID- 29633057
TI  - Transurethral vaporesection of prostate: diode laser or thulium laser?
AB  - This study compared the safety and effectiveness of the diode laser and thulium
      laser during prostate transurethral vaporesection for treating benign prostate
      hyperplasia (BPH). We retrospectively analyzed 205 patients with BPH who
      underwent a diode laser or thulium laser technique for prostate transurethral
      vaporesection from June 2016 to June 2017 and who were followed up for 3 months.
      Baseline characteristics of the patients, perioperative data, postoperative
      outcomes, and complications were compared. We also assessed the International
      Prostate Symptom Score (IPSS), quality of life (QoL), maximum flow rate (Qmax),
      average flow rate (AFR), and postvoid residual volume (PVR) at 1 and 3 months
      postoperatively to evaluate the functional improvement of each group. There were
      no significant differences between the diode laser and thulium laser groups
      related to age, prostate volume, operative time, postoperative hospital stays,
      hospitalization costs, or perioperative data. The catheterization time was 3.5 +/
      0.8 days for the diode laser group and 4.7 +/- 1.8 days for the thulium laser
      group (p < 0.05). Each group had dramatic improvements in IPSS, QoL, Qmax, AFR,
      and PVR compared with the preoperative values (p < 0.05), although there were no
      significant differences between the two groups. Use of both diode laser and
      thulium laser contributes to safe, effective transurethral vaporesection in
      patients with symptomatic BPH. Diode laser, however, is better than thulium laser
      for prostate transurethral vaporesection because of its shorter catheterization
      time. The choice of surgical approach is more important than the choice of laser
      types during clinical decision making for transurethral laser prostatectomy.

PMID- 29633058
TI  - Peritoneum as an origin of epilepsy from the viewpoint of Avicenna.
AB  - There are studies that show that the concepts of epilepsy have been rooted in
      Persian medicine; Avicenna "Ibn-e-Sina"-one of the great Persian physicians in
      the Islamic golden age (9th-12th century AD)-has considered some types of
      epilepsy with the association of the stomach, the spleen, the "Maraqq," and the
      whole body which has not been reviewed properly. These organs influence on the
      brain and can cause epilepsy. This article presents concept of Maraqq-related
      epilepsy; according to Avicenna's view, "Maraqq" is a membranous structure which
      is located in the abdomen (equivalent of parietal peritoneum in current
      nomenclature). We discuss his viewpoint about the diagnosis and treatment of
      Maraqq-related epilepsy with focus on herbal remedies. The concept of a
      relationship between the "Maraqq" and the brain is well discussed in the old
      Persian medicine texts; however, it seems that further studies in this area are
      required to clarify Avicenna's view about the pathophysiological mechanisms,
      clinical manifestations, and treatment strategies.

PMID- 29633059
TI  - Transition from acute kidney injury to chronic kidney disease: a single-centre
      cohort study.
AB  - BACKGROUND: The incidence of acute kidney injury (AKI) is increasing. AKI is
      currently recognised as an inducer of chronic kidney disease (CKD) and this is
      known as the 'AKI-CKD transition'. This study aimed to evaluate the rate of
      decline in estimated glomerular filtration rate (eGFR) associated with AKI events
      in individuals with and without pre-existing CKD. METHODS: Inpatients aged 18-80
      years were retrospectively enrolled. AKI was diagnosed according to the kidney
      disease improving global outcomes (KDIGO) criteria using serum creatinine levels.
      Patients with a history of AKI events were divided into four groups according to
      eGFR before and after the AKI events. In each group, the eGFR levels after an AKI
      event were compared to those before the AKI event. Patients were further divided
      into eight groups according to clinical background based on underlying diseases,
      medications, and surgical history. RESULTS: We analysed data from 9651 patients
      with AKI. Not surprisingly, we found that eGFR levels during the first AKI event
      were significantly lower than levels before the event in each group. Furthermore,
      eGFR levels after the first AKI event were significantly lower than those before
      the first AKI event, and the eGFR levels after the second AKI event were
      significantly lower than those after the first AKI event. These trends were
      similar in each group irrespective of clinical background. CONCLUSIONS: Our study
      revealed that AKI events can cause a decline in kidney function and, as more AKI
      events occur, acceleration of this decline.

PMID- 29633060
TI  - Comparing the Healthcare Utilization and Engagement in a Sample of Transgender
      and Cisgender Bisexual+ Persons.
AB  - People who identify as non-monosexual and transgender experience disparities in
      engagement with healthcare services relative to monosexual and cisgender persons,
      respectively. However, little is known about the healthcare utilization of those
      with intersecting sexual and gender minority identities. We explored the
      knowledge, attitudes, and health motivation of non-monosexually identified
      transgender participants regarding preventive care and access to sexual
      healthcare services. We surveyed 87 ciswomen, 34 transwomen, and 27 transmen, all
      of whom identified as bisexual, pansexual, or queer (bi+). We assessed their
      access to health care, health outcome experiences, confidence with talking about
      anogenital topics, proactivity toward their health, comfort with healthcare
      providers, and knowledge about HPV and examined differences across groups. The
      data indicated that bi+ transmen and transwomen were more likely to be uninsured
      or on a government-sponsored insurance plan relative to bi+ ciswomen. Only a
      minority of transmen and transwomen had seen an obstetrician/gynecologist
      compared with ciswomen. Transmen were less likely to have received a pelvic
      examination or cervical Pap smear in their lifetime. Transgender participants had
      significantly less correct knowledge about HPV relative to ciswomen. Finally,
      relative to ciswomen, transgender participants reported lower comfort talking
      with health providers. Our findings suggest that bi+ transmen and transwomen
      access care less than bi+ ciswomen and have less health knowledge and comfort
      with their providers. Implications for intervention include encouraging
      transgender individuals to seek routine screenings, reducing structural barriers
      to care based on medical coverage, and improving patient-provider competencies
      around bi+ and transgender health needs.

PMID- 29633061
TI  - Physical Health Disparities Across Dimensions of Sexual Orientation,
      Race/Ethnicity, and Sex: Evidence for Increased Risk Among Bisexual Adults.
AB  - Accumulating evidence suggests that sexual minority individuals are at increased
      risk for physical health conditions compared to heterosexual individuals.
      However, we know little about physical health disparities affecting bisexual
      individuals, a population at increased risk for psychiatric and substance use
      conditions compared to both heterosexual and lesbian/gay populations. Using a
      large, nationally representative sample, we examined physical health disparities
      for bisexual individuals. To advance research on sexual minority health
      disparities, we further: (1) compared prevalence rates of physical health
      conditions across three dimensions of sexual orientation (i.e., identity,
      attractions, behavior) and (2) examined whether disparities differed by sex and
      race/ethnicity. Results indicated that sexual minority individuals were at
      increased risk for many physical health conditions. Notably, individuals with
      bisexual identity, attractions, and/or behavior were at increased risk for more
      physical health conditions than other sexual minority groups. The number and
      types of physical health disparities affecting bisexually identified individuals
      and individuals with same- and opposite-sex attractions and/or sexual partners
      varied across sex and race/ethnicity, with the most consistent disparities
      emerging for individuals who reported same- and opposite-sex sexual partners. Our
      findings highlight the substantial physical health disparities affecting sexual
      minorities and the heightened risk conferred by all facets of bisexuality.

PMID- 29633062
TI  - The decision to discontinue screening for carnitine uptake disorder in New
      Zealand.
AB  - When screening for carnitine uptake disorder (CUD), the New Zealand (NZ) newborn
      screening (NBS) service identified infants as screen-positive if they had initial
      and repeat free carnitine (C0) levels of less than 5.0 MUmol/L. Since 2006, the
      NBS service has identified two infants with biochemical and genetic features
      consistent with neonatal CUD and nine mothers with features consistent with
      maternal CUD. A review of the literature suggests that these nine women reflect
      less than half the true prevalence and that CUD is relatively common. However,
      the NZ results (two infants) suggest a very low sensitivity and positive
      predictive value of NBS. While patients presenting with significant disease due
      to CUD are well described, the majority of adults with CUD are asymptomatic.
      Nonetheless, treatment with high-dose oral L-carnitine is recommended. Compliance
      with oral L-carnitine is likely to be poor long term. This may represent a
      specific risk as treatment could repress the usual compensatory mechanisms seen
      in CUD, such that a sudden discontinuation of treatment may be dangerous. L
      carnitine is metabolized to trimethylamine-N-oxide (TMAO) and treated patients
      have extremely high plasma TMAO levels. TMAO is an independent risk factor for
      atherosclerosis and, thus, caution should be exercised regarding long-term
      treatment with high-dose carnitine of asymptomatic patients who may have a
      biochemical profile without disease. Due to these concerns, the NZ Newborn
      Metabolic Screening Programme (NMSP) initiated a review via a series of advisory
      and governance committees and decided to discontinue screening for CUD.

PMID- 29633063
TI  - Establishment and characterization of cell clones from the Papilio cell line RIRI
      PaDe-3 by a high-efficiency clonal method.
AB  - Cell cloning is of great importance in keeping particular properties of cultured
      cells, and interesting cells can be selected by cloning from heterogeneous cell
      populations. In addition, continuous cell lines usually from primary culture are
      prone to heterologous constitution and genetic instability, so that supplementary
      cloning steps are necessary for achieving a homogenous cell population. In this
      study, limiting dilution culture and feeder layer culture were originally used
      for cloning RIRI-PaDe-3 cell line, but both failed. Afterward, we designed a
      cloning protocol which was composed of two steps: cells in semisolid medium with
      seeding density in the range of 3.05 * 105-6.10 * 105 cells/mL formed colonies
      from monodispersed cell suspensions; 40 well-dispersed colonies were removed from
      the suspended state by using micromanipulator system and finally scaled up. To
      determine whether this method can isolate cell lines possessing characteristics
      different from the parent population, we made an evaluation of cells monoclonal
      in biological characteristics. Significant differences have been found among
      clones isolated from the RIRI-PaDe-3 insect cell line in cell morphology,
      chromosome numbers, and genetic background. Thus the indicated modified semisolid
      medium cloning protocol was advantageous to the convenient and genuine cloning
      from the previously heterogeneous population.

PMID- 29633064
TI  - Expression profile of long non-coding RNAs during the differentiation of human
      umbilical cord derived mesenchymal stem cells into cardiomyocyte-like cells.
AB  - We aimed to investigate the differentially expressed long non-coding RNAs
      (lncRNAs) during the differentiation of human umbilical cord derived mesenchymal
      stem cells (hUCMSCs) into cardiomyocyte-like cells induced by 5-aza. hUCMSCs were
      isolated and purified from umbilical cords. After treated with 10 MUmol/L 5-Aza
      for 24 h, hUCMSCs wereas continued to be cultured for 14 days. Comparison of
      cardiac specific genes and the expression profile of lncRNAs on hUCMSCs between
      day 14 and day 0 was performed using immunofluorescence staining,
      immunohistochemistry, Western blot assay, RT-PCR and lncRNA microarray. Results
      show that well-organized sarcomeric structure and more cTnI and MLC2a staining
      were seen in hUCMSCs of day 14 after 5-aza-induced compared to those in day 0.
      Expression of Desmin, Nkx2.5, cTnI and MLC2a of hUCMSCs was much higher on day 14
      compared with day 0 (P < 0.01). 41 differentially expressed lncRNAs were found on
      day 14 hUCMSCs compared those of day 0 were identified. Among them, 25
      upregulated and 16 downregulated. Four out of the five upregulated lncRNAs (P =
      0.00035, 0.014, 0.016 and 0.005 for uc010vei.1, X72487, BC064139, AK092074) and
      four out of the five downregulated lncRNAs (P = 0.038, 0.0014, 0.00026 and 0.004
      for X85157, uc007keu.1, AK309872, NR_029399) showed significantly different
      expressions in further validation using RT-PCR. Our results illustrated that
      there was a dysregulation of the lncRNA profile during the differentiation of
      hUCMSCs into cardiomyocyte-like cells, which will provide the foundation for
      further study of the biological functions and mechanism of lncRNAs in the
      differentiation of hUCMSCs into cardiomyocyte-like cells.

PMID- 29633065
TI  - KDM4B promotes DNA damage response via STAT3 signaling and is a target of CREB in
      colorectal cancer cells.
AB  - Resistance to radiotherapy is a major limitation for the successful treatment of
      colorectal cancer (CRC). Recently, accumulating evidence supports a critical role
      of epigenetic regulation in tumor cell survival upon irradiation. Lysine
      Demethylase 4B (KDM4B) is a histone demethylase involved in the oncogenesis of
      multiple human cancers but the underlying mechanisms have not been fully
      elucidated. Here we show that KDM4B is overexpressed in human colorectal cancer
      (CRC) tumors and cell lines. In CRC cells, KDM4B silencing induces spontaneous
      double-strand breaks (DSBs) formation and potently sensitizes tumor cells to
      irradiation. A putative mechanism involved suppression of Signal Transducer and
      Activator of Transcription 3 (STAT3) signaling pathway, which is essential for
      efficient repair of damaged DNA. Overexpression of STAT3 in KMD4B knockdown cells
      largely attenuates DNA damage triggered by KDM4B silencing and increases cell
      survival upon irradiation. Moreover, we find evidence that transcription factor
      CAMP Responsive Element Binding Protein (CREB) is a key regulator of KMD4B
      expression by directly binding to a conserved region in KMD4B promoter. Together,
      our findings illustrate the significance of CREB-KDM4B-STAT3 signaling cascade in
      DNA damage response, and highlight that KDM4B may potentially be a novel
      oncotarget for CRC radiotherapy.

PMID- 29633066
TI  - Reversal of dabigatran using idarucizumab: single center experience in four acute
      stroke patients.
AB  - Dabigatran is a direct thrombin inhibitor and a non-vitamin-K-antagonizing oral
      anticoagulant, approved for the prevention of stroke and systemic embolization in
      atrial fibrillation. Idarucizumab is a humanized monoclonal antibody that was
      recently approved for antagonizing the anticoagulant effects of dabigatran. Here,
      we report the use of idarucizumab in four acute stroke patients treated with
      dabigatran in order to enable intravenous thrombolysis in three patients and
      emergent trepanation in one patient with space occupying subdural hematoma. Since
      experience on the optimal management of acute stroke patients under medication
      with dabigatran and on the use of idarucizumab is currently limited, we propose
      an approach for laboratory testing and fast administration of intravenous
      thrombolysis and neurosurgery based on our experience.

PMID- 29633067
TI  - What is the importance of real-time three dimensional transesophageal
      echocardiography and time in therapeutic range in patients with prosthetic valve
      thrombosis?

PMID- 29633068
TI  - Cerebral venous sinus thrombosis complicated by seizures.

PMID- 29633069
TI  - Health Care Access and Utilization Among U.S. Immigrants Before and After the
      Affordable Care Act.
AB  - We examine changes in health insurance coverage and access to and utilization of
      health care before and after the national implementation of the Patient
      Protection and Affordable Care Act (ACA) among the U.S. adult immigrant
      population. Data from the 2011-2016 National Health Interview Survey are used to
      compare adult respondents in 2011-2013 (before the ACA implementation) and 2014
      2016 (after the ACA implementation). Multivariable logistic regression analyses
      are used to compare changes over time. This study shows that the ACA has closed
      the coverage gap that previously existed between U.S. citizens and non-citizen
      immigrants. We find that naturalized citizens, non-citizens with more than 5
      years of U.S. residency, and non-citizens with 5 years or less of U.S. residency
      reduced their probability of being uninsured by 5.81, 9.13, and 8.23%,
      respectively, in the first 3 years of the ACA. Improvements in other measures of
      access and utilization were also observed.

PMID- 29633071
TI  - Anxiolytic-like effects of paeoniflorin in an animal model of post traumatic
      stress disorder.
AB  - Post-traumatic stress disorder (PTSD) is the serious psychiatric disorder.
      Paeoniflorin (PF) produces the antidepressant-like properties. However, few
      studies are concerned about its anti-PTSD-like effects and mechanisms. To
      investigate these, the single prolonged stress (SPS) model was utilized. PTSD
      like behavioral deficits in rats after exposure to SPS were improved by PF (10
      and 20 mg/kg, i.p.), evidenced by blocking increased freezing time in contextual
      fear paradigm (CFP) and increased time and entries in open arms in elevated plus
      maze (EPM) test without affecting the locomotor activity in open field (OF) test.
      We also found that increased levels of corticosterone (Cort), corticotropin
      releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) after exposure to
      SPS were reversed by PF (10 and 20 mg/kg, i.p.) in serum, respectively. Moreover,
      the decreased levels of serotonin (5-HT) and 5-Hydroxyindoleacetic acid (5-HIAA)
      in prefrontal cortex and hippocampus were reversed by PF (10 and 20 mg/kg, i.p.),
      respectively. In summary, the anti-PTSD-like activities of PF were associated
      with the modulation of HPA axis and 5-HT system activation.

PMID- 29633070
TI  - Management of idiopathic recurrent pericarditis in adults and in children: a role
      for IL-1 receptor antagonism.
AB  - Recurrent pericarditis is one of the most frequent pericardial diseases,
      affecting up to 30% of the patients who have experienced acute pericarditis.
      While the diagnosis of acute pericarditis is sometime straight forward, its
      etiology and therapeutic management are still a challenge for physicians. In
      developed countries, the idiopathic form is the most frequent, and the search for
      an infectious etiology is almost invariably negative. Nevertheless, since
      standard treatment with nonsteroidal anti-inflammatory drugs and colchicine is
      not always able to neutralize pericardial inflammation in recurrent pericarditis,
      anakinra, an IL-1 receptor antagonist, has been proposed as a possible
      therapeutic alternative for refractory forms. IL-1 is a cytokine that exerts a
      pivotal role in innate immunity and in the pathogenesis of some autoimmune
      diseases, such as rheumatoid arthritis, and in autoinflammatory disorders, as
      familial Mediterranean fever and cryopyrin-associated periodic syndromes. The
      successful management of patients with acute idiopathic recurrent pericarditis
      (IRP) needs a teamwork approach, where cardiologists, rheumatologists, clinical
      immunologists and internists are involved. In this review, we will discuss the
      clinical and therapeutical challenges of IRP both in adults and children from a
      clinical practice standpoint. We will also briefly illustrate the main pathogenic
      mechanisms of IRP to provide internists and cardiologists with the rationale for
      approaching the use of anakinra in selected clinical cases.

PMID- 29633072
TI  - Association of Expression Levels or Activation Status of STAT3 with Treatment
      Outcomes of Sunitinib in Patients with Renal Cell Carcinoma.
AB  - BACKGROUND: The expression level of signal transducer and activator of
      transcription 3 (STAT3) in tumor cells is reported to associate with response to
      therapy and with survival time in various types of cancer. OBJECTIVE: This
      retrospective study aimed to elucidate the association of STAT3 expression in
      tumor cells with the therapeutic outcomes of sunitinib in patients with renal
      cell carcinoma (RCC). PATIENTS AND METHODS: Patients with metastatic RCC who
      received sunitinib therapy were enrolled in this study. All patients underwent
      nephrectomy for RCC, and nephrectomy specimens were stained for STAT3 and
      phosphorylated STAT3 (p-STAT3) by immunohistochemistry. RESULTS: We assessed 51
      patients receiving sunitinib as a first-line therapy. STAT3 expression levels did
      not influence progression-free survival (PFS) and overall survival (OS); however,
      patients with p-STAT3-positive tumors exhibited significantly worse PFS compared
      with those with p-STAT3-negative tumors (log-rank test, P = 0.034). OS tended to
      be prolonged in patients with p-STAT3-negative tumors. Objective response rate or
      disease control rate based on the best overall response did not show a
      significant association with STAT3 or p-STAT3 expression. Univariate Cox
      proportional hazard regression analyses for clinical predictors revealed that p
      STAT3 positivity significantly correlated with shorter PFS (hazard ratio [HR],
      2.22, P = 0.041), whereas p-STAT3 expression was not related to the OS.
      CONCLUSIONS: Activated STAT3 in tumor tissues shows a significant association
      with poor prognosis in patients with RCC who received sunitinib as a first-line
      therapy, and positive p-STAT3 expression could be a potential biomarker for
      refractoriness to sunitinib therapy.

PMID- 29633074
TI  - Limitation of flatfoot surgery in overcorrected clubfeet after extensive surgery.
AB  - INTRODUCTION: Flatfoot is a severe complication of extensive clubfoot surgery. In
      this retrospective study, we evaluated our results following flatfoot surgery in
      overcorrected clubfeet. The aim was to analyze the success of different surgical
      techniques, including tarsal osteotomies and arthrodesis, in correcting different
      types of flatfeet. MATERIAL AND METHOD: Between January 1, 2011 and December 31,
      2015 we treated 25 severe cases of flatfeet after extensive clubfoot surgery. We
      classified the hindfoot deformities into rotational valgus, hinge valgus or
      translatory valgus based on AP standing X-rays. Tarsal osteotomies (Mitchell,
      Evans, Cotton) and arthrodesis were adapted based on age and severity. Age,
      gender, pain, hindfoot valgus and function were documented. Function and X-rays
      were compared pre- and postoperatively. RESULTS: There were 17 male and 4 female
      patients. Age at operation ranged from 11 to 26 years with an average age of 14.3
      years. The mean follow-up was 27.6 months (7-60 months). Primary surgical
      treatment was a tarsal osteotomy in 19 cases and in six cases it was arthrodesis.
      Hindfoot valgus (O 18.6 degrees -3.2 degrees ), calcaneal pitch (O 6.2 degrees 
      14.6 degrees ), Costa Bartani angle (O155 degrees -142 degrees ) and Meary angle
      (O 2.0 degrees -8.8 degrees ) improved pre- to postoperatively. Range of motion
      did not improve after surgical correction. 81% were satisfied with the
      postoperative results. All flatfeet with translatory valgus, initially treated
      with a tarsal osteotomy, needed further arthrodesis due to primary
      undercorrection. CONCLUSION: Tarsal osteotomies are successful methods for
      correcting flatfeet following extensive clubfoot surgery with rotational valgus
      and mild hinge valgus. Tarsal osteotomies are unable to successfully correct
      flatfeet that have a translatory valgus. In such cases, we recommend double or
      triple arthrodesis. The functional outcome is limited by the preop range of
      motion and the appearance of talus deformities.

PMID- 29633073
TI  - Moderate High Temperature Condition Induces the Lactation Capacity of Mammary
      Epithelial Cells Through Control of STAT3 and STAT5 Signaling.
AB  - In lactating mammary glands, alveolar mammary epithelial cells (MECs) synthesize
      and secrete milk components. MECs also form less permeable tight junctions (TJs)
      to prevent the leakage of milk components. During lactation, MECs are exposed to
      temperature changes by metabolic heat production and air ambient temperature. In
      this study, we investigated whether temperature changes influence milk production
      ability and TJ barriers in MECs by using two lactating culture models. The
      results showed that 39  degrees C treatment activated milk production and
      enhanced the formation of less-permeable TJs. In contrast, 41  degrees C
      treatment caused adverse effects on the TJ barrier and cell viability, although
      the milk production ability of MECs was temporarily up-regulated. MECs cultured
      at 37  degrees C showed relatively low milk production ability and high
      proliferation activity. Furthermore, we investigated three kinds of transcription
      factors relating to lactogenesis, signal transducer and activator of
      transcription 5 (STAT5), STAT3 and glucocorticoid receptor (GR). STAT5 signaling
      was activated at 39 and 41  degrees C by an increase in total STAT5. However,
      long-term treatment led to a decrease in total STAT5. STAT3 signaling was
      inactivated by high temperature treatment through a decrease in total STAT3 and
      inhibited phosphorylation of STAT3. GR signaling was continuously activated
      regardless of temperature. These results indicate that a moderate high
      temperature condition at 39  degrees C induces a high lactation capacity of MECs
      through control of STAT5 and STAT3 signaling. In contrast, long-term exposure at
      41  degrees C leads to a decline in milk production capacity by inactivation of
      STAT5 and a decrease in the total number of MECs.

PMID- 29633075
TI  - Intralesional vs. extralesional procedures for low-grade central chondrosarcoma:
      a systematic review of the literature.
AB  - INTRODUCTION: Chondroid lesions are very common bone tumors. In most cases, they
      are benign enchondromas (EC) and, in a minor percentage, chondrosarcomas (CSs),
      the malignant counterpart. In the latter cases, surgery is the mainstay
      treatment, because they are chemo- and radio-resistant unless dedifferentiation
      occurs. If resection is recognized as the gold standard for intermediate-, high
      grade tumors, and for low-grade chondrosarcoma (LG-CS) located in the spine and
      pelvis to reduce the risk of local recurrence, there is still no consensus in
      literature on the treatment of central low-grade chondrosarcoma (cLG-CS) located
      in the limbs. Our aim is to perform a review of literature on evidence supporting
      this approach or not. MATERIALS AND METHODS: An electronic research of the
      medical archives was carried out in March 2017 seeking papers evaluating the
      results of curettage and resection in cLG-CS. RESULTS: We selected 13 studies
      corresponding to our criteria. Unfortunately, they were descriptive,
      retrospective, non-randomized studies. We identified a population of 471 patients
      for a total of 473 low-grade chondrosarcomas. Two hundred and ninety-nine lesions
      were treated with curettage and 174 with wide surgery. The two groups were not
      homogeneous for diagnosis, size and staging, so no comparison between resection
      and curettage was possible. The global weighted average percentage of local
      recurrence was 6.7% (20 cases) and 10.9% (19 cases) after curettage and
      resection, respectively. No cases of metastasis were reported in the group
      treated with intralesional surgery, compared to five cases reported in the group
      treated with resection. Indications for surgery were given in most cases based on
      symptoms and imaging. CONCLUSIONS: The absence of a preoperative histological
      diagnosis and the lack of a scientific method to conduct the studies do not
      sufficiently support curettage for low-grade chondrosarcomas. In the absence of
      this, resection must be considered a general rule for every malignancy. In our
      opinion, based on the low biological growth rate of low-grade chondrosarcoma,
      every chondromatous lesion can be followed-up. Biopsies must be performed based
      on clinical and radiological suspicions such as pain, scalloping or increase in
      size, rather than on performing a PET scan to evidence more informative high
      metabolic areas.

PMID- 29633076
TI  - Functional growth inhibition of influenza A and B viruses by liquid and powder
      components of leaves from the subtropical plant Melia azedarach L.
AB  - We evaluated the anti-influenza-virus effects of Melia components and discuss the
      utility of these components. The effects of leaf components of Melia azedarach L.
      on viruses were examined, and plaque inhibition tests were performed. The in vivo
      efficacy of M. azedarach L. was tested in a mouse model. Leaf components of Melia
      azedarach L. markedly inhibited the growth of various influenza viruses. In an
      initial screening, multiplication and haemagglutination (HA) activities of H1N1,
      H3N2, H5, and B influenza viruses were inactivated by the liquid extract of
      leaves of M. azedarach L. (MLE). Furthermore, plaque inhibition titres of H1N1,
      H3N2, and B influenza viruses treated with MLE ranged from 103.7 to 104.2. MLE
      possessed high plaque-inhibitory activity against pandemic avian H5N1, H7N9, and
      H9N2 vaccine candidate strains, with a plaque inhibition titre of more than
      104.2. Notably, the buoyant density decreased from 1.175 to 1.137 g/cm3, and
      spikeless particles appeared. We identified four anti-influenza virus substances:
      pheophorbide b, pheophorbide a, pyropheophorbide a, and pheophytin a.
      Photomorphogenesis inside the envelope may lead to removal of HA and
      neuraminidase spikes from viruses. Thus, MLE could efficiently remove floating
      influenza virus in the air space without toxicity. Consistent with this finding,
      intranasal administration of MLE in mice significantly decreased the occurrence
      of pneumonia. Additionally, leaf powder of Melia (MLP) inactivated influenza
      viruses and viruses in the intestines of chickens. MLE and MLP may have
      applications as novel, safe biological disinfectants for use in humans and
      poultry.

PMID- 29633077
TI  - Surveillance of HIV-1 drug resistance in Xinjiang: high prevalence of K103N in
      treatment-naive individuals.
AB  - To identify transmitted and acquired HIV-1 drug resistance mutations in Xinjiang,
      China, we collected the peripheral blood of 50 treated and 50 treatment-naive HIV
      1-infected individuals in this region. We successfully amplified 36 reverse
      transcriptase and 42 protease gene sequences of HIV-1 from 51 individuals and
      identified mutations associated with resistance to reverse transcriptase (RT) and
      protease (PR) inhibitors (RTIs and PIs) according to Stanford Drug Resistance
      Database. Among the drug-treated individuals, the results showed that K103N in
      the RT region was the most frequent mutation, found in 67% (6/9) of the cases,
      followed by M184V with 56% (5/9). Five individuals had both nucleoside and non
      nucleoside reverse transcriptase inhibitor resistance mutations after more than
      12 months of treatment. Among the untreated individuals, 33% (9/27) were found to
      harbor drug resistance mutations in the RT gene. K103N occurred at the highest
      rate, accounting for 22% (6/27), followed by P225H (7%) and Y188L (4%). Neither
      of the two groups showed any major resistance mutations to PIs. Our study
      revealed that the prevalence of drug resistance was relatively high in Xinjiang
      and that K103N occurred at the highest rate. These results suggest that it is
      important to carry out HIV drug resistance testing, especially for the K103N
      mutation in the RT region, before and during the treatment process. This study
      may help to guide ART strategies in the Xinjiang region.

PMID- 29633078
TI  - Antiviral activity of Embelia ribes Burm. f. against influenza virus in vitro.
AB  - Viral respiratory infections are raising serious concern globally. Asian
      medicinal plants could be useful in improving the current treatment strategies
      for influenza. The present study examines the activity of five plants from
      Bangladesh against influenza virus. MDCK cells infected with influenza virus
      A/Puerto Rico/8/34 (H1N1) were treated with increasing concentrations of ethyl
      acetate extracts, and their cytotoxicity (CC50), virus-inhibiting activity
      (IC50), and selectivity index (SI) were calculated. The ethyl acetate extract of
      fruits of Embelia ribes Burm. f. (Myrsinaceae) had the highest antiviral
      activity, with an IC50 of 0.2 ug/mL and a SI of 32. Its major constituent,
      embelin, was further isolated and tested against the same virus. Embelin
      demonstrated antiviral activity, with an IC50 of 0.3 uM and an SI of 10. Time-of
      addition experiments revealed that embelin was most effective when added at early
      stages of the viral life cycle (0-1 h postinfection). Embelin was further
      evaluated against a panel of influenza viruses including influenza A and B
      viruses that were susceptible or resistant to rimantadine and oseltamivir. Among
      the viruses tested, avian influenza virus A/mallard/Pennsylvania/10218/84 (H5N2)
      was the most susceptible to embelin (SI = 31), while A/Aichi/2/68 (H3N2) virus
      was the most resistant (SI = 5). In silico molecular docking showed that the
      binding site for embelin is located in the receptor-binding domain of the viral
      hemagglutinin. The results of this study provide evidence that E. ribes can be
      used for development of a novel alternative anti-influenza plant-based agent.

PMID- 29633079
TI  - Safety and efficacy of single-fraction gamma knife radiosurgery for benign
      confined cavernous sinus tumors: our experience and literature review.
AB  - Gamma knife radiosurgery (GKRS) has emerged as a suitable primary treatment
      option for confined cavernous sinus tumors (CSTs) and residual/recurrent benign
      tumors extending from the surrounding neighborhood. The aim of this review was to
      further investigate the safety and efficacy of single-fraction GKRS for primary
      confined CSTs (hemangioma, meningioma, and schwannoma). This was a retrospective
      analysis of 16 patients of CSTs, primarily treated with GKRS between 2009 and
      2017. The patients underwent follow-up clinical and radiological evaluation at a
      regular interval. Data on clinical and imaging parameters were analyzed. The
      published literature on GKRS for CSTs was reviewed. There were total 16 patients
      (eight meningiomas, seven hemangiomas, and one schwannoma). Patients presented
      with a headache (56.3%), ptosis (50%), and/or restricted extraocular movements
      (50%). There was 46.6% tumor volume (TV) reduction after single-fraction GKRS.
      Hemangiomas showed best TV reduction (64% reduction at > 3-year follow-up)
      followed by schwannoma (41.5%) and meningioma (25.4%). 56.3% of patients
      developed transient hypoesthesia in trigeminal nerve distribution. 44.4% of
      patients became completely pain-free. Among cranial nerves, the superior division
      of the oculomotor nerve showed best outcome (ptosis 62.5%) followed by an
      improved range of EOM. There was no adverse event in the form of new-onset
      deficit, vascular complication, or malignant transformation except for one out of
      the field failures. Among available treatment options, GKRS is the most suitable
      option by virtue of its minimally invasive nature, optimal long-term tumor
      control, improvement in cranial neuropathies, cost-effectiveness, favorable risk
      benefit ratio, and minimal long-term complications.

PMID- 29633080
TI  - Culturing conditions highly affect DNA methylation and gene expression levels in
      MCF7 breast cancer cell line.
AB  - The levels of DNA methylation and their role in gene expression are key factors
      that could affect diagnosis, prognosis, and treatment options of different
      diseases. In this study, the methylation levels of 22 genes that are mostly
      correlated to breast cancer were determined using EpiTect methyl II PCR array.
      This analysis was performed to determine the effect of cells' passage number and
      the use of antibiotics in the culturing media on gene methylation levels in MCF7
      cell line. DNA methylation levels of PTGS2, ADAM23, HIC1, and PYCARD were found
      to be significantly different among different passages. While the DNA methylation
      levels of CCNA1, RASSF1, and THBS1 were found to be affected by the use of 1% of
      penicillin/streptomycin in the culture media. Gene expression analysis after
      demethylation using 5-Aza-2'-deoxycytidine showed that the gene expression levels
      of the hypermethylated genes varied between different passage numbers. This study
      shows that the presence of antibiotic within cultured media and cell line's
      passage number could greatly affect the methylation levels that need to be
      considered in future studies on cell lines.

PMID- 29633081
TI  - An intraoperative fluoroscopic method to accurately measure the post-implantation
      position of pedicle screws.
AB  - PURPOSE: Pedicle screw malplacement, leading to neurological symptoms, vascular
      injury, and premature implant loosening, is not uncommon and difficult to
      reliably detect intraoperatively with current techniques. We propose a new
      intraoperative post-placement pedicle screw position assessment system that can
      therefore allow surgeons to correct breaches during the procedure. Our objectives
      were to assess the accuracy and robustness of this proposed screw location system
      and to compare its performance to that of 2D planar radiography. METHODS: The
      proposed system uses two intraoperative X-ray shots acquired with a standard
      fluoroscopic C-arm and processed using 2D/3D registration methods to provide a 3D
      visualization of the vertebra and screw superimposed on one another. Point
      digitization and CT imaging of the residual screw tunnel were used to assess
      accuracy in five synthetic lumbar vertebral models (10 screws in total).
      Additionally, the accuracy was evaluated with and without correcting for image
      distortion and for various screw lengths, screw materials, breach directions, and
      vertebral levels. RESULTS: The proposed method is capable of localizing the
      implanted screws with less than 2 mm of translational error (RMSE: 0.7 and 0.8 mm
      for the screw head and tip, respectively) and less than [Formula: see text]
      angular error (RMSE: [Formula: see text]), with minimal change to the errors if
      image distortion is not corrected. Breaches and their anatomical locations were
      all correctly visualized and identified for a variety of screw lengths, screw
      materials, breach locations, and vertebral levels, demonstrating the robustness
      of this approach. In contrast, one breach, one non-breach, and the anatomical
      location of three screws were misclassified with 2D X-ray. CONCLUSION: We have
      demonstrated an accurate and low-radiation technique for localizing pedicle
      screws post-implantation that requires only two X-rays. This intraoperative
      feedback of screw location and direction may allow the surgeon to correct
      malplaced screws intraoperatively, thereby reducing postoperative complications
      and reoperation rates.

PMID- 29633082
TI  - Monoclonal Antibody-Based Serological Detection Methods for Wheat Dwarf Virus.
AB  - Wheat dwarf disease caused by wheat dwarf virus (WDV) is currently present in
      wheat growing regions in China and causes serious losses in wheat yield. To
      develop reliable and effective serological detection methods for WDV, the coat
      protein (CP) gene of WDV was cloned and expressed in Escherichia coli. The
      purified recombinant CP protein was immunized to BALB/c mice, and four hybridoma
      cell lines (i.e. 18G10, 9G4, 23F4 and 22A10) secreting anti-WDV monoclonal
      antibodies (MAbs) were obtained through the hybridoma technique. Using the
      prepared MAbs, an antigen-coated-plate enzyme-linked immunosorbent assay (ACP
      ELISA) and a dot-ELISA were established for detecting WDV in wheat samples. The
      most sensitive ACP-ELISA based on MAb 23F4 or 22A10 was able to detect WDV in
      1:163,840 (w/v, g/mL) diluted WDV-infected wheat plant crude extracts. The dot
      ELISA based on MAb 23F4 was the most sensitive and able to detect the virus in
      1:5,120 (w/v, g/mL) diluted wheat plant crude extracts. A total of 128 wheat
      samples were collected from wheat growing regions in the Shaanxi and Qinghai
      provinces, China, and were screened for the presence of WDV using two developed
      serological assays. Results from the survey showed that approximately 62% of the
      samples were infected with WDV. PCR followed by DNA sequencing and sequence
      alignment validated the results from the two serological assays. Therefore, we
      consider that these two serological detection methods can be significantly useful
      for the control of WDV in China.

PMID- 29633083
TI  - Contrast-enhanced intraoperative ultrasound in the resection of colorectal liver
      metastases with intrabiliary growth.
AB  - A 68-year-old male who had undergone low anterior resection for primary rectal
      cancer 19 months ago presented with multiple CLM at Couinaud's segments IV, V,
      and VIII. There was no apparent macroscopic intrabiliary growth on preoperative
      computed tomography and gadolinium ethoxybenzyl diethylenetriamine pentaacetic
      acid-enhanced magnetic resonance imaging (EOB-MRI). However, the hepatobiliary
      phase of EOB-MRI revealed peritumoral low signal intensity in lesions in segments
      V and VIII, which indicates vascular invasion around hepatocellular carcinoma.
      Contrast-enhanced intraoperative ultrasound (CE-IOUS) clearly determined the
      extent of macroscopic glissonean growth from lesions in segments V and VIII, and
      more extensive resection was performed than was planned. Analysis of the resected
      specimens from segments V and VIII confirmed the presence of macroscopic
      intrabiliary growth with microscopic portal vein invasion. All three CLM were
      histopathologically diagnosed as well-to-moderately differentiated
      adenocarcinoma, and R0 resection was verified. Postoperative recovery was
      uneventful, and the patient was alive without evidence of recurrence 12 months
      after hepatic resection. CE-IOUS should be considered at the time of CLM
      resection, as it might enable more accurate detection of macroscopic intrabiliary
      growth of CLM, and enable resection with safer margins.

PMID- 29633085
TI  - Transcutaneous tibial nerve stimulation: 2 years follow-up outcomes in the
      management of anticholinergic refractory overactive bladder.
AB  - PURPOSE: To evaluate long-term use, efficacy and tolerability of transcutaneous
      tibial nerve stimulation (TTNS) in the treatment of refractory overactive bladder
      (OAB). METHODS: We performed a prospective observational study and included all
      patients treated in a single center for OAB persisting after first-line
      anticholinergic treatment, with >= 24 months follow-up. The protocol consisted of
      daily stimulation at home. The primary outcome was treatment persistence.
      Amelioration was defined as an improvement in urinary symptom profile (USP)
      score. RESULTS: We assessed 84 consecutive patients. After a mean follow-up of
      39.3 months and a mean treatment use of 8.3 months, almost two-thirds of patients
      (71.8%) had discontinued TTNS. Treatment continuation was > 12 months for 28
      patients (33.3%) and > 18 months for 16 patients (19%). TTNS was successful
      following 3 months of treatment in 60 (71%) patients. Mean USP score stayed
      significantly lower than baseline until 12 months of treatment, but was not
      significant anymore after 18 months. Discontinuation therapy reasons were a lack
      of sufficient symptom relief for 59 (70%) patients, compliance difficulty for 5
      (6%) patients and becoming asymptomatic for 6 (8%) patients. No serious adverse
      events occurred. CONCLUSIONS: The present study confirms the utility of TTNS as a
      treatment option for patients with resistant OAB. In the long-term use, few
      patients continued with therapy, mostly because of a decreased effectiveness with
      time.

PMID- 29633086
TI  - Silica diatom shells tailored with Au nanoparticles enable sensitive analysis of
      molecules for biological, safety and environment applications.
AB  - Diatom shells are a natural, theoretically unlimited material composed of silicon
      dioxide, with regular patterns of pores penetrating through their surface. For
      their characteristics, diatom shells show promise to be used as low cost, highly
      efficient drug carriers, sensor devices or other micro-devices. Here, we
      demonstrate diatom shells functionalized with gold nanoparticles for the
      harvesting and detection of biological analytes (bovine serum albumin-BSA) and
      chemical pollutants (mineral oil) in low abundance ranges, for applications in
      bioengineering, medicine, safety, and pollution monitoring.

PMID- 29633087
TI  - Development of an Autism Subtyping Questionnaire Based on Social Behaviors.
AB  - Autism spectrum disorder can be differentiated into three subtypes (aloof,
      passive, and active-but-odd) based on social behaviors according to the Wing
      Subgroups Questionnaire (WSQ). However, the correlations between the scores on
      some individual items and the total score are poor. In the present study, we
      translated the WSQ into Chinese, modified it, validated it in autistic and
      typically-developing Chinese children, and renamed it the Beijing Autism
      Subtyping Questionnaire (BASQ). Our results demonstrated that the BASQ had
      improved validity and reliability, and differentiated autistic children into
      these three subtypes more precisely. We noted that the autistic symptoms tended
      to be severe in the aloof, moderate in the passive, and mild in the active-but
      odd subtypes. The modified questionnaire may facilitate etiological studies and
      the selection of therapeutic regimes.

PMID- 29633084
TI  - Applied Sport Science of Australian Football: A Systematic Review.
AB  - BACKGROUND: In recent years, there has been a large expansion in literature
      pertaining to the game of Australian football (AF). Furthermore, there have been
      a number of rule changes that are likely to have changed the demands of the game.
      Based on these advances and changes, it seemed important to conduct a review
      assessing the scientific literature surrounding the sport. OBJECTIVE: The review
      evaluates the match demands of AF, the qualities required for success, and the
      impact training and competition have on adaptation, injury and fatigue. METHODS:
      A systematic search of PubMed, CINAHL, SPORTDiscus, Web of Science and Scopus for
      AF literature was conducted; studies investigating match demands, physical
      qualities, training practices and injury were included. Weighted means and
      standard deviations were calculated for match demands and physical and
      anthropometric profiles across playing standards. RESULTS: A total of 1830
      articles were retrieved in the initial search, with 888 removed as duplicates,
      626 removed for being non-relevant and a further 152 removed for being AF papers
      but not relevant to the review. As such, 164 AF papers were included in the
      review. Due to the intermittent high-intensity nature of match-play, players need
      a wide range of physical and technical qualities to excel, with speed, aerobic
      fitness, reactive agility and well-developed lean mass being central to success.
      Training for AF at the elite level is associated with high workloads, with
      players engaging in numerous training modalities; even altitude and heat training
      camps have been utilised by Australian Football League (AFL) teams to further
      augment fitness improvements. While high chronic workloads can be tolerated and
      are needed for improving physical qualities, careful planning and monitoring of
      internal and external workloads is required to minimise sharp spikes in load that
      are associated with injury. CONCLUSIONS: There is a complex interaction between
      numerous contextual factors that influence the match demands that are discussed
      in this review. Whilst players must have the physical capacities to cope with the
      intense physical demands of AF matches, the successful execution of technical
      skills during match-play is central to success. To develop these skills and
      attributes, specific and carefully planned and monitored training must be
      performed over a number of years.

PMID- 29633088
TI  - Dual Antithrombotic Therapy with Clopidogrel and Novel Oral Anticoagulants in
      Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention:
      A Real-world Study.
AB  - INTRODUCTION: For patients with atrial fibrillation (AF) undergoing percutaneous
      coronary intervention (PCI), proper antithrombotic therapy is equivocal. Current
      guidelines recommend triple therapy, which carries a high risk of bleeding.
      Recent large trials suggest that dual therapy (DT) with novel oral anticoagulant
      (NOAC) plus P2Y12 inhibitor can be an appropriate alternative, but real-world
      data for this alternative are scarce and the optimal duration of DT has not yet
      been established. METHODS: This analysis was performed in a single-center
      prospective cohort. We investigated 216 PCI patients with indication for
      anticoagulation due to AF. After PCI patients received DT with reduced doses NOAC
      plus P2Y12 inhibitor for 6 months, which was followed by standard dose NOAC
      monotherapy. Efficacy endpoints were defined as cardiac death, myocardial
      infarction (MI), stent thrombosis (ST), and stroke. Safety endpoints were
      bleeding events as defined by Bleeding Academic Consortium (BARC). RESULTS:
      Baseline characteristics of our study population were described by a CHA2DS2-VASc
      score of greater than 4 and a HAS-BLED score of greater than 3. After a mean
      follow-up of 18.7 months, efficacy events occurred in 12 patients (5.6%). We
      observed three (1.4%) cardiac deaths, two (0.9%) MIs, six (2.8%) strokes, and one
      (0.5%) definite ST. After switching from DT to NOAC monotherapy after 6.3 +/- 1.7
      months, there was no rebound of ischemic events. Bleeding events occurred in 34
      patients (15.7%) mainly under DT, while bleeding was less during NOAC
      monotherapy. CONCLUSIONS: In this long-term study of high-risk and real-world AF
      patients with PCI, DT with NOAC and P2Y12 inhibitor (6 months) followed by NOAC
      monotherapy was safe and effective.

PMID- 29633091
TI  - Vitamins for Prevention of Contrast-induced Acute Kidney Injury: A Systematic
      Review and Trial Sequential Analysis.
AB  - BACKGROUND: To date, universally accepted preventive measures for contrast
      induced acute kidney injury (CI-AKI) do not exist, and they warrant further
      research. OBJECTIVE: The purpose of this study was to evaluate the efficacy of
      vitamins, including vitamin C and E, for prevention of CI-AKI. METHODS: We
      electronically searched the MEDLINE, EMBASE, and Cochrane databases. The outcome
      of interest was the incidence of CI-AKI. RESULTS: A total of 19 studies were
      included in this meta-analysis. Pooled analysis showed that vitamin C plus saline
      [relative risk (RR) = 0.63, 95% confidence interval (CI) 0.49-0.82, p = 0.0005]
      and vitamin E plus saline (RR = 0.39, 95% CI 0.24-0.62, p < 0.0001) significantly
      reduced the incidence of CI-AKI compared to saline alone. The effect of vitamin C
      plus saline was further confirmed by trial sequential analysis (TSA). However,
      TSA indicated that more trials are required to confirm the efficacy of vitamin E
      plus saline. There was no significant difference in preventing CI-AKI between
      vitamin C and N-acetylcysteine (NAC) (RR = 0.90, 95% CI 0.47-1.71, p = 0.75),
      between vitamin C plus NAC and saline (RR = 0.62, 95% CI 0.30-1.30, p =  0.20),
      as well as between vitamin C plus NAC and NAC (RR = 0.97, 95% CI 0.49-1.92, p =
      0.93). CONCLUSIONS: Vitamin C plus saline administration is effective at reducing
      the risk of CI-AKI. Evidence for the use of vitamin E plus saline in this context
      is encouraging, but more trials are required. Furthermore, this meta-analysis and
      TSA indicated insufficient power to draw a definitive conclusion on the effect of
      vitamin C plus NAC, versus saline or NAC alone, which needs to be explored
      further.

PMID- 29633089
TI  - Herbal Dietary Supplements for Erectile Dysfunction: A Systematic Review and Meta
      Analysis.
AB  - PURPOSE: Erectile dysfunction (ED) is a common condition that significantly
      affects quality of life and interpersonal relationships. OBJECTIVE: Our objective
      was to perform a systematic review and meta-analysis to evaluate the efficacy of
      herbal dietary supplements in the treatment of ED. MATERIALS AND METHODS: We
      searched five databases to identify randomized controlled trials (RCTs) that
      evaluated the clinical efficacy of herbal medicines in ED. Quality was assessed
      and risk of bias was estimated using the Jadad score and the Cochrane risk-of
      bias tool. RESULTS: In total, 24 RCTs, including 2080 patients with ED, were
      identified. Among these, 12 evaluated monopreparations (five ginseng [n = 399],
      three saffron [n = 397], two Tribulus terrestris [n = 202], and one each Pinus
      pinaster [n = 21] and Lepidium meyenii [n = 50]), seven evaluated formulations (n
      = 544), and five investigated dietary supplements in combination with pure
      compounds (n = 410). Ginseng significantly improved erectile function
      (International Index of Erectile Function [IIEF]-5 score: 140 ginseng, 96
      placebo; standardized mean difference [SMD] 0.43; 95% confidence interval [CI]
      0.15-0.70; P < 0.01; I2 = 0), P. pinaster and L. meyenii showed very preliminary
      positive results, and saffron and T. terrestris treatment produced mixed results.
      Several herbal formulations were associated with a decrease of IIEF-5 or IIEF-15,
      although the results were preliminary. The quality of the included studies
      varied, with only seven having a prevalent low risk of bias. The median
      methodological quality Jadad score was three out of a maximum of five. Adverse
      events were recorded in 19 of 24 trials, with no significant differences between
      placebo and verum in placebo-controlled studies. CONCLUSIONS: Encouraging
      evidence suggests that ginseng may be an effective herbal treatment for ED.
      However, further, larger, and high-quality studies are required before firm
      conclusions can be drawn. Promising (although very preliminary) results have also
      been generated for some herbal formulations. Overall, more research in the field,
      adhering to the CONSORT statement extension for reporting trials, is justified
      before the use of herbal products in ED can be recommended.

PMID- 29633092
TI  - Dissolution and Translational Modeling Strategies Enabling Patient-Centric Drug
      Product Development: the M-CERSI Workshop Summary Report.
AB  - On May 15th-17th, 2017, the US FDA and the International Consortium for
      Innovation and Quality in Pharmaceutical Development (IQ) held a workshop at the
      University of Maryland's Center of Excellence in Regulatory Science and
      Innovation (M-CERSI), to discuss the role of dissolution testing and
      translational modeling and simulation in enabling patient-centric solid oral drug
      product development. This 3-day event was attended by scientists from regulatory
      agencies, pharmaceutical companies, and academia. The workshop included podium
      presentations followed by breakout session discussions. The first day of the
      meeting focused on the challenges in dissolution method development and the role
      of dissolution testing throughout drug product development. On the second day,
      approaches to establish a link between in vitro testing and in vivo drug product
      performance (e.g., systemic exposure) were presented. Overall success rates and
      challenges in establishing IVIVCs via traditional and modern physiologically
      based pharmacokinetic (PBPK) modeling and simulation approaches were discussed.
      Day 3 provided an opportunity to discuss the expectations for establishing
      clinically relevant drug product specifications (CRDPS). It was recognized that
      understanding the impact of formulation and process variations on dissolution and
      in vivo performance is critical for most drug products formulated with poorly
      soluble drugs to ensure consistent product performance. The breakout sessions
      served as platforms for discussing controversial topics such as the clarification
      of dissolution terminology, PBPK model development and validation expectations,
      and approaches to set CRDPS. The meeting concluded with a commitment to continue
      the dialog between regulators, industry, and academia to advance overall product
      quality understanding.

PMID- 29633093
TI  - Delivery of molecular cargoes in normal and cancer cell lines using non-viral
      delivery systems.
AB  - OBJECTIVE: In this study, transfection efficiency of human papillomavirus (HPV)
      E7 DNA and protein constructs into HEK-293T normal cell line, and A549 and TC-1
      tumor cell lines was evaluated by four delivery systems including supercharge
      GFP, hPP10 cell penetrating peptide, TurboFect and Lipofectamine using
      fluorescence microscopy and flow cytometry. RESULTS: The results indicated that
      Lipofectamine 2000 and TurboFect produced more effective transfection for GFP and
      E7-GFP DNA constructs in HEK-293T cells compared to in A549 and TC-1 cells (p <
      0.05). In contrast, the supercharge GFP was efficient for E7 DNA and E7 protein
      delivery in both normal cell (~ 83.94 and ~ 77.01% for HEK-293T), and cancer
      cells (~ 71.69 and ~ 67.19% for TC-1, and ~ 73.86 and ~ 67.49% for A549),
      respectively. Indeed, in these cell lines, transfection efficiency by +36 GFP
      reached ~ 60-80%. Moreover, the hPP10 produced the best transfection result for
      E7-GFP protein in HEK-293T cells (~ 63.66%) compared to TurboFect (~ 32.95%);
      however, the efficiency level of hPP10 was only ~ 17.51 and ~ 16.36% in TC-1 and
      A549 cells. CONCLUSIONS: Our data suggested that the supercharge GFP is the most
      suitable transfection vehicle for DNA and protein delivery into TC-1 and A549
      tumor cell lines compared to other carriers.

PMID- 29633094
TI  - Determinants of HIV Incidence Disparities Among Young and Older Men Who Have Sex
      with Men in the United States.
AB  - This study sought to determine why young men who have sex with men (MSM) have
      higher HIV incidence rates than older MSM in the United States. We developed
      hypotheses that may explain this disparity. Data came from peer-reviewed studies
      published during 1996-2016. We compared young and older MSM with respect to
      behavioral, clinical, psychosocial, and structural factors that promote HIV
      vulnerability. Compared with older MSM, young MSM were more likely to have HIV
      discordant condomless receptive intercourse. Young MSM also were more likely to
      have "any" sexually transmitted infection and gonorrhea. Among HIV-positive MSM,
      young MSM were less likely to be virally suppressed, use antiretroviral therapy,
      and be aware of their infection. Moreover, young MSM were more likely than older
      MSM to experience depression, polysubstance use, low income, decreased health
      care access, and early ages of sexual expression. These factors likely converge
      to exacerbate age-associated HIV incidence disparities among MSM.

PMID- 29633095
TI  - Long-Term Outcomes of Gastric Cancer Patients with Preoperative Sarcopenia.
AB  - BACKGROUND: There are few reports of long-term outcomes of gastric cancer
      patients with sarcopenia. The purpose of this study was to assess the impact of
      sarcopenia on long-term outcomes in gastric cancer patients who underwent
      curative resection. METHODS: A total of 951 patients aged 65 years or older who
      underwent R0 resection for gastric cancer were investigated. Sarcopenia was
      defined as a decreased arm muscle area < 38.05 cm2 in men and < 27.87 cm2 in
      women combined with a decline in grip strength to < 26 kgf in men and < 18 kgf in
      women. RESULTS: Of 951 patients, 111 (11.7%) were diagnosed with sarcopenia.
      Reduced surgery was performed significantly more frequently in patients with
      sarcopenia (p = 0.006). The incidence of eligible patients who received adjuvant
      chemotherapy was significantly lower in patients with sarcopenia than in those
      without sarcopenia (p = 0.030). Mortality due to gastric cancer and aging
      associated multiple organ failure rates without obvious diseases were higher in
      patients with sarcopenia (p = 0.036 and p < 0.001, respectively). Overall
      survival (OS) and cause-specific survival (CSS) were significantly worse in
      patients with sarcopenia (p < 0.001 and p = 0.005, respectively). Multivariate
      analysis for OS and CSS revealed that sarcopenia was an independent prognostic
      factor in gastric cancer patients (p < 0.001 and p = 0.043, respectively).
      CONCLUSIONS: Sarcopenia is related to poor survival in gastric cancer patients
      and appears to be a significant negative prognostic factor in patients with
      gastric cancer who underwent curative resection.

PMID- 29633096
TI  - Efficacy of Endoscopic Management for Early Remnant Gastric Cancer: Is Completion
      Gastrectomy Truly Necessary in Cases with Marginally Noncurative Histopathologic
      Features?
AB  - BACKGROUND: For patients with early primary gastric cancer, endoscopic management
      has become a standard of care. However, its efficacy for early remnant gastric
      cancer (ERGC) remains controversial and an invasive surgical procedure remains
      the primary choice of treatment. METHODS: A multi-institutional database of ERGC
      cases was retrospectively reviewed. Efficacy of endoscopic resection was analyzed
      by reviewing the clinicopathologic features of patients who underwent endoscopic
      resection and comparing the long-term outcomes with those of surgical resection.
      RESULTS: Of the 121 patients who were histopathologically diagnosed with ERGC
      after distal gastrectomy, 80 underwent endoscopic resection and 41 underwent
      completion gastrectomy (Group S). According to the histopathological criteria, 55
      of the 80 endoscopic resection cases were classified as "curative resection"
      (Group E1) and the remaining 25 were classified as "noncurative resection" (Group
      E2). Tumor recurrence was observed only in three patients (12%) in Group E2, and
      no tumor recurrence was confirmed in Group S and Group E1. Multivariate analyses
      confirmed that completion gastrectomy [hazard ratio (HR), 6.2; 95% confidence
      interval (CI), 1.5-26.3] was associated with poor survival compared with
      endoscopic resection, and lymphovascular infiltration (HR 9.5; 95% CI 2.5-36.7)
      was correlated with tumor recurrence. Histopathological positive resection
      margin, tumor size, or deeper tumor invasion were not correlated with tumor
      recurrence after endoscopic resection. CONCLUSIONS: Endoscopic management might
      be an effective treatment option for ERGC with potential long-term survival
      advantage over the completion gastrectomy even in cases with histopathological
      features, suggesting noncurative resection.

PMID- 29633097
TI  - Stage- and Histologic Subtype-Dependent Frequency of Lymph Node Metastases in
      Patients with Epithelial Ovarian Cancer Undergoing Systematic Pelvic and
      Paraaortic Lymphadenectomy.
AB  - PURPOSE: Tumor stage and distinct histological subtypes in epithelial ovarian
      cancer (EOC) show different prognostic outcome. The aim of this study is to
      evaluate whether the frequency of lymph node (LN) metastases in patients with
      different tumor stages and histological subtypes undergoing systematic pelvic and
      paraaortic lymphadenectomy is coincidentally divergent. METHODS: Patients with
      EOC treated with upfront staging or debulking surgery between January 2000 and
      December 2016 were included. Systematic lymphadenectomy was performed in all
      consecutive patients with optimal debulking and without medical
      contraindications. RESULTS: Seven hundred sixty-two patients including 27.2% with
      early-stage EOC were included. The median number of removed LNs was 69, and
      metastases to LNs were found in 54.7%. No LN metastases were found in patients
      with low-grade endometrioid carcinoma, independently of tumor stage. LN
      metastases in early-stage low-grade serous (N = 5), mucinous (N = 31), and clear
      cell (N = 28) EOC were found in one (20%), zero, and one (3.6%) patient,
      respectively. LN metastases were detected in more than 10% of patients with all
      other histological subtypes. On multivariate analyses, overall survival was
      significantly impaired in patients with LN metastases, as compared with patients
      without LN metastases (p = 0.001). CONCLUSIONS: The risk of LN metastases in
      patients with EOC is dependent on stage and histological subtype. Patients with
      incidental finding of early mucinous or low-grade endometrioid EOC are at very
      low risk of retroperitoneal lymph node metastases. Reoperation for lymph node
      staging only should be discussed individually with caution.

PMID- 29633098
TI  - How Old is Too Old? Breast Cancer Treatment in Octogenarians.

PMID- 29633099
TI  - Use of the MIRUSTM system for general anaesthesia during surgery: a comparison of
      isoflurane, sevoflurane and desflurane.
AB  - The MIRUSTM system enables automated end-expired control of volatile
      anaesthetics. The device is positioned between the Y-piece of the breathing
      system and the patient's airway. The system has been tested in vitro and to
      provide sedation in the ICU with end-expired concentrations up to 0.5 MAC. We
      describe its performance in a clinical setting with concentrations up to 1.0 MAC.
      In 63 ASA II-III patients undergoing elective hip or knee replacement surgery,
      the MIRUSTM was set to keep the end-expired desflurane, sevoflurane, or
      isoflurane concentration at 1 MAC while ventilating the patient with the PB-840
      ICU ventilator. After 1 h, the ventilation mode was switched from controlled to
      support mode. Time to 0.5 and 1 MAC, agent usage, and emergence times, work of
      breathing, and feasibility were assessed. In 60 out of 63 patients 1.0 MAC could
      be reached and remained constant during surgery. Gas consumption was as follows:
      desflurane (41.7 +/- 7.9 ml h-1), sevoflurane (24.3 +/- 4.8 ml h-1) and
      isoflurane (11.2 +/- 3.3 ml h-1). Extubation was faster after desflurane use
      (min:sec): desflurane 5:27 +/- 1:59; sevoflurane 6:19 +/- 2:56; and isoflurane
      9:31 +/- 6:04. The support mode was well tolerated. The MIRUSTM system reliable
      delivers 1.0 MAC of the modern inhaled agents, both during mechanical ventilation
      and spontaneous (assisted) breathing. Agent usage is highest with desflurane
      (highest MAC) but results in the fastest emergence. Trial registry number:
      Clinical Trials Registry, ref.: NCT0234509.

PMID- 29633100
TI  - Management and Outcome of Liver Abscesses After Liver Transplantation.
AB  - BACKGROUND: Liver abscess after orthotopic liver transplantation (OLT) is a rare,
      life-threatening complication. The aim of this study is to analyze the incidence,
      risk factors, clinical manifestations, treatment and outcomes of liver abscesses
      after OLT. METHODS: We perform a retrospective review of the patients who
      developed one or more liver abscesses among a series of 984 patients who
      underwent OLT between January 2000 and December 2016. RESULTS: Fourteen patients
      (1.5%) developed 18 episodes of liver abscesses, and the median time from OLT to
      the diagnosis of liver abscess was 39.7 months. Major predisposing factors were
      biliary strictures in 11 patients, hepatic artery thrombosis in 8, re-OLT in 3,
      choledochojejunostomy in 2, living donor OLT in 2, donor after cardiac death in
      1, split liver in 1, and liver biopsy in 1. All patients were managed by
      intravenous antibiotics; percutaneous drainage was performed in 10 patients,
      while 2 patients underwent re-OLT. The mortality rate related to liver abscesses
      was 21.4%. The mean hospital stay was 30 +/- 19 days, and during a mean follow-up
      of 93 +/- 78 months, three other patients died. CONCLUSIONS: Liver abscesses must
      be managed with antibiotic therapy and percutaneous drainage, but when these
      conservative measures fail (persistent abscess and sepsis), a re-OLT must be
      performed in order to prevent the high mortality associated with this severe
      complication.

PMID- 29633101
TI  - Association Between Circular Stapler Diameter and Stricture Rates Following
      Gastrointestinal Anastomosis: Systematic Review and Meta-analysis.
AB  - BACKGROUND: Stricture is a common complication of gastrointestinal (GI)
      anastomoses, associated with impaired quality of life, risk of malnutrition, and
      further interventions. This systematic review and meta-analysis aimed to
      determine the association between circular stapler diameter and anastomotic
      stricture rates throughout the GI tract. METHODS: A systematic literature search
      of EMBASE, MEDLINE and Cochrane Library was performed. The primary outcome was
      the rate of radiologically or endoscopically confirmed anastomotic stricture.
      Pooled odds ratios (OR) were calculated using random-effects models to determine
      the effect of circular stapler diameter on stricture rates in different regions
      of the GI tract. RESULTS: Twenty-one studies were identified: seven oesophageal,
      twelve gastric, and three lower GI. Smaller stapler sizes were strongly
      associated with higher anastomotic stricture rates throughout the GI tract. The
      oesophageal anastomosis studies showed; 21 versus 25 mm circular stapler: OR 4.39
      ([95% CI 2.12, 9.07]; P < 0.0001); 25 versus 28/29 mm circular stapler: OR 1.71
      ([95% CI 1.15, 2.53]; P < 0.008). Gastric studies showed; 21 versus 25 mm
      circular stapler: OR 3.12 ([95% CI 2.23, 4.36]; P < 0.00001); 25 versus 28/29 mm
      circular stapler: OR 7.67 ([95% CI 1.86, 31.57]; P < 0.005). Few lower GI studies
      were identified, though a similar trend was found: 25 versus 28/29 mm circular
      stapler: pooled OR 2.61 ([95% CI 0.82, 8.29]; P = 0.100). CONCLUSIONS: The use of
      larger circular stapler sizes is strongly associated with reduced risk of
      anastomotic stricture in the upper GI tract, though data from lower GI joins are
      limited.

PMID- 29633102
TI  - Inequalities in Implementation and Different Outcomes During the Growth of
      Laparoscopic Colorectal Cancer Surgery in England: A National Population-Based
      Study from 2002 to 2012.
AB  - AIM: Laparoscopic colorectal cancer surgery has developed from unproven technique
      to mainstay of treatment. This study examined the application and relative
      outcomes of laparoscopic and open colorectal cancer surgery over time, as
      laparoscopic uptake and experience have grown. METHODS: Adults undergoing
      elective laparoscopic and open colorectal cancer surgery in the English NHS
      during 2002-2012 were included. Age, sex, Charlson Comorbidity Index and Index of
      Multiple Deprivation were compared over time. Post-operative 30-day mortality,
      length of stay, failure to rescue reoperation and the associated mortality rate
      were examined. RESULTS: Laparoscopy rates rose from 1.1 to 50.8%. Patients
      undergoing laparoscopic surgery had lower comorbidity by 0.24 points (95%
      confidence intervals (CI) 0.20-0.27) and lower socioeconomic deprivation by 0.16
      deciles (95% CI 0.12-0.20) than those having open procedures. Overall mortality
      fell by 48.0% from 2002-2003 to 2011-2002 and was 37.8% lower after laparoscopic
      surgery. Length of stay and mortality after surgical re-intervention also fell.
      However, re-intervention rates were higher after laparoscopic procedures by 7.8%
      (95% CI 0.9-15.2%). CONCLUSIONS: There was clear and persistent inequality in the
      application of laparoscopic colorectal cancer surgery during this study. Further
      work must explore and remedy inequalities to maximise patient benefit. Higher re
      intervention rates after laparoscopy are unexplained and differ from randomized
      controlled trials. This may reflect differences in surgeons and practice between
      research and usual care settings and should be further investigated.

PMID- 29633103
TI  - Vinpocetine Ameliorates Acetic Acid-Induced Colitis by Inhibiting NF-kappaB
      Activation in Mice.
AB  - The idiopathic inflammatory bowel diseases (IBD) comprise two types of chronic
      intestinal disorders: Crohn's disease and ulcerative colitis. Recruited
      neutrophils and macrophages contribute to intestinal tissue damage via production
      of ROS and NF-kappaB-dependent pro-inflammatory cytokines. The introduction of
      anti-TNF-alpha therapies in the treatment of IBD patients was a seminal advance.
      This therapy is often limited by a loss of efficacy due to the development of
      adaptive immune response, underscoring the need for novel therapies targeting
      similar pathways. Vinpocetine is a nootropic drug and in addition to its
      antioxidant effect, it is known to have anti-inflammatory and analgesic
      properties, partly by inhibition of NF-kappaB and downstream cytokines.
      Therefore, the present study evaluated the effect of the vinpocetine in a model
      of acid acetic-induced colitis in mice. Treatment with vinpocetine reduced edema,
      MPO activity, microscopic score and macroscopic damage, and visceral mechanical
      hyperalgesia. Vinpocetine prevented the reduction of colonic levels of GSH, ABTS
      radical scavenging ability, and normalized levels of anti-inflammatory cytokine
      IL-10. Moreover, vinpocetine reduced NF-kappaB activation and thereby NF-kappaB
      dependent pro-inflammatory cytokines IL-1beta, TNF-alpha, and IL-33 in the colon.
      Thus, we demonstrate for the first time that vinpocetine has anti-inflammatory,
      antioxidant, and analgesic effects in a model of acid acetic-induced colitis in
      mice and deserves further screening to address its suitability as an approach for
      the treatment of IBD.

PMID- 29633104
TI  - Brazilian green propolis hydroalcoholic extract reduces colon damages caused by
      dextran sulfate sodium-induced colitis in mice.
AB  - This study investigated the effects of Brazilian green propolis hydroalcoholic
      extract (BPE) in 3% w/v dextran sodium sulfate (DSS)-induced colitis in mice. The
      effects of BPE (3, 30 and 300 mg/kg, p.o, by 7 days) on the morphological (colon
      length and colon weight), clinical (disease activity index and weight loss),
      microscopic (histological score and mucin levels) and biochemical parameters were
      determined. The effects of BPE (300 mg/kg, p.o) in the gastrointestinal transit
      of mice were also evaluated. As expected, the DSS ingestion damaged the colonic
      tissue, lowered the body weight, decreased the mucin levels, increased MPO
      activity, reduced SOD activity and GSH amount. In contrast, the treatment with
      BPE (300 mg/kg) significantly reduced macroscopic colonic injury and the mucosal
      damage in colon on histopathological examination and reversed the decrease in
      mucin levels induced by DSS. It also significantly normalized the SOD activity
      and the levels of GSH, but did not elicit any effect on MPO activity in the
      colon. In addition, BPE did not change the gastric emptying or the intestinal
      transit rate of mice. Together, these results suggested that BPE reduced the
      signs of DSS-induced colitis in mice through maintenance of intestinal mucin
      barrier and favoring intestinal antioxidant defenses.

PMID- 29633105
TI  - Curcumin-galactomannoside complex inhibits pathogenesis in Ox-LDL-challenged
      human peripheral blood mononuclear cells.
AB  - Oxidised low-density lipoprotein (ox-LDL) is a pro-atherogenic molecule, which
      induces inflammatory response and contributes to the pathogenesis of vascular
      dysfunction to atherosclerosis. The aim of the present study was to explore the
      anti-inflammatory effect of a novel bioavailable formulation of curcumin as
      'curcumagalactomannosides' (CGM) against ox-LDL-induced inflammatory responses in
      human peripheral blood mononuclear cells (hPBMCs). Curcumagalactomannosides was
      made from natural curcumin using the soluble dietary fibre (galactomannans)
      derived from fenugreek seeds (Trigonella foenumgracum) and the hPBMCs were
      isolated from healthy human volunteers. The cells were cultured in collagen
      coated plates at 37  degrees C and grouped as Group I (Control), Group II (ox-LDL
      treated) and Group III (ox-LDL + CGM treated). Further analysis of inflammatory
      markers, reactive oxygen species and mRNA expression levels indicated
      significantly increased expressions of iNOS, TNF-alpha, IL-6 and VCAM-1 in ox-LDL
      treated group along with the nuclear translocation of NF-kappaB. Other
      inflammatory markers such as LOX, PGE2, total COX and lipid peroxidation level
      were also found to be significantly (p < 0.05) increased upon ox-LDL treatment.
      The treatment with CGM on the other hand was found to down-regulate and reverse
      the ox-LDL-induced alterations indicating its potential anti-inflammatory effect
      on hPBMCs via. NF-kappaB signalling pathway.

PMID- 29633106
TI  - Probiotic mixture of Lactobacillus and Bifidobacterium alleviates systemic
      adiposity and inflammation in non-alcoholic fatty liver disease rats through
      Gpr109a and the commensal metabolite butyrate.
AB  - AIMS: The study explored the systemic adiposity and inflammation through Gpr109a
      and the commensal metabolite butyrate during the treatment of non-alcoholic fatty
      liver disease rats with the probiotic mixture of Lactobacillus and
      Bifidobacterium for 16 weeks. METHODS: Fifteen male SD rats were randomly divided
      into three groups of five rats each: normal control group (basal feed), high-fat
      diet (HFD) feeding group (83% basal feed + 10% lard oil + 5% sucrose + 1.5%
      cholesterol + 0.5% cholate), and probiotic mixture intervention group (HFD + 0.6
      g kg-1 day-1 probiotic mixture). Body composition, serum lipids, serum
      inflammatory markers, Gpr109a, and the commensal metabolite butyrate were
      assessed. RESULTS: Compared with HFD group, probiotic mixture significantly
      reduced body weight and the levels of serum FFA, TG, ALT, IL-1beta, and IL-18 (P
      < 0.05). The levels of Gpr109a and the commensal metabolite butyrate also changed
      significantly (P < 0.05). CONCLUSIONS: Probiotic mixture might inhibit systemic
      adiposity and inflammation through Gpr109a and the commensal metabolite butyrate
      in response to the insult of HFD.

PMID- 29633107
TI  - Freshmen at a University in Appalachia Experience a Higher Rate of Campus than
      Family Food Insecurity.
AB  - Food insecurity means having limited or uncertain access, in socially acceptable
      ways, to an adequate and safe food supply. Ample evidence has identified college
      students as vulnerable to this problem, but little research has focused on
      freshmen. This cross-sectional study examined family and campus food insecurity
      among freshmen at a university in Appalachia. An online questionnaire contained
      sociodemographic items and scales that measured food security status, academic
      progress, coping strategies for accessing food, and social support. T-tests and
      Chi square analyses compared food insecure and food secure students. Statistical
      significance was p < .05. Participants were 456 freshmen, 118 males (26%) and 331
      females (73%). Family and campus food insecurity were experienced by 32 (7.1%)
      and 98 (21.5%) of the freshmen, respectively, and 42.5% of those who experienced
      campus food insecurity believed their food access had worsened since starting
      college. Family and campus coping strategies, respectively, included stretching
      food (72.9 vs. 18.4%) and purchasing cheap, processed food (68.8 vs. 16.3%). Food
      secure students scored significantly higher on self-rated measures of academic
      progress (p < .01), and greater proportions of food secure students (60.7 vs.
      43.9%, p < .01) perceived their eating habits since starting college as
      "healthy/very healthy," and perceived their health status as "good/excellent"
      (86.0 vs. 71.4%, p < .01). Students requested assistance with job opportunities
      (19.4%), affordable meal plans (18.4%), money management (13.3%), and eating
      healthy (11.2%). Findings suggest that college student food insecurity begins
      during the freshmen year, and that there is a need for campus and community-based
      interventions to increase food access among these freshmen and their families.

PMID- 29633108
TI  - A Simple Ultrasound Based Classification Algorithm Allows Differentiation of
      Benign from Malignant Breast Lesions by Using Only Quantitative Parameters.
AB  - PURPOSE: We hypothesized that different quantitative ultrasound (US) parameters
      may be used as complementary diagnostic criteria and aimed to develop a simple
      classification algorithm to distinguish benign from malignant breast lesions and
      aid in the decision to perform biopsy or not. PROCEDURES: One hundred twenty-four
      patients, each with one biopsy-proven, sonographically evident breast lesion,
      were included in this prospective, IRB-approved study. Each lesion was examined
      with B-mode US, Color/Power Doppler US and elastography (Acoustic Radiation Force
      Impulse-ARFI). Different quantitative parameters were recorded for each
      technique, including pulsatility (PI) and resistive Index (RI) for Doppler US and
      lesion maximum, intermediate, and minimum shear wave velocity (SWVmax, SWVinterm,
      and SWVmin) as well as lesion-to-fat SWV ratio for ARFI. Receiver operating
      characteristic curve (ROC) analysis was used to evaluate the diagnostic
      performance of each quantitative parameter. Classification analysis was performed
      using the exhaustive chi-squared automatic interaction detection method. Results
      include the probability for malignancy for every descriptor combination in the
      classification algorithm. RESULTS: Sixty-five lesions were malignant and 59
      benign. Out of all quantitative indices, maximum SWV (SWVmax), and RI were
      included in the classification algorithm, which showed a depth of three
      ramifications (SWVmax <= or > 3.16; if SWVmax <= 3.16 then RI <= 0.66, 0.66-0.77
      or > 0.77; if RI <= 0.66 then SWVmax <= or > 2.71). The classification algorithm
      leads to an AUC of 0.887 (95 % CI 0.818-0.937, p < 0.0001), a sensitivity of
      98.46 % (95 % CI 91.7-100 %), and a specificity of 61.02 % (95 % CI 47.4-73.5 %).
      By applying the proposed algorithm, a false-positive biopsy could have been
      avoided in 61 % of the cases. CONCLUSIONS: A simple classification algorithm
      incorporating two quantitative US parameters (SWVmax and RI) shows a high
      diagnostic performance, being able to accurately differentiate benign from
      malignant breast lesions and lower the number of unnecessary breast biopsies in
      up to 60 % of all cases, avoiding any subjective interpretation bias.

PMID- 29633109
TI  - Selective Pragmatic Impairment in Autism Spectrum Disorder: Indirect Requests
      Versus Irony.
AB  - Autism Spectrum Disorder (ASD) is often described as being characterised by a
      uniform pragmatic impairment. However, recent evidence suggests that some areas
      of pragmatic functioning are preserved. This study seeks to determine to which
      extent context-based derivation of non-linguistically encoded meaning is
      functional in ASD. We compare the performance of 24 adults with ASD, and matched
      neuro-typical adults in two act-out pragmatic tasks. The first task examines
      generation of indirect request interpretations, and the second the comprehension
      of irony. Intact contextual comprehension of indirect requests contrasts with
      marked difficulties in understanding irony. These results suggest that preserved
      pragmatics in ASD is limited to egocentric processing of context, which does not
      rely on assumptions about the speaker's mental states.

PMID- 29633110
TI  - Efficacy of intrathecal chemotherapy in patients with central nervous system
      involvement of hematological malignancies: a retrospective analysis.
AB  - INTRODUCTION: Central nervous system (CNS) involvement, especially involvement of
      the cerebrospinal fluid (CSF), is common in several haematological malignancies.
      Intrathecal (IT) chemotherapy can be used to manage CSF involvement. METHODS:
      Here we evaluated the effectiveness of IT chemotherapy among 80 patients with
      haematological malignancies and CSF localization who were treated with IT
      chemotherapy from 2001 to 2012. RESULTS: The majority of patients was diagnosed
      with diffuse large B-cell lymphoma (26%) or acute lymphoblastic
      leukaemia/lymphoblastic lymphoma (19%). After first-line IT chemotherapy, which
      mainly consisted of methotrexate (MTX) and corticosteroids, CSF complete response
      (CSF CR) was achieved in 76% of patients. 91% reached CSF CR when including
      second-line IT-chemotherapy. Clinical response was documented in 75%. Although
      most patients were additionally treated with systemic chemotherapy, response rate
      did not differ between patients treated with CNS-penetrating and CNS-non
      penetrating drugs. CNS progression/relapse occurred in 40% of patients with
      median progression-free survival of 12.2 months. The median overall survival was
      18.3 months; 55% of the patients died during follow-up. CONCLUSIONS: Our analysis
      shows a high response rate after first-line IT chemotherapy, but also a
      relatively high progression/relapse percentage.

PMID- 29633111
TI  - Tumor growth dynamics in serially-imaged low-grade glioma patients.
AB  - BACKGROUND: Diffuse low-grade gliomas (LGGs) are infiltrative, slow-growing
      primary brain tumors that remain relatively asymptomatic for long periods of time
      before progressing into aggressive and fatal high-grade gliomas. METHODS: We
      retrospectively identified LGG patients with numerous (>= 8) serial magnetic
      resonance imaging (MRI) studies. Tumor volumes were measured by manual
      segmentation on serial imaging to study the natural history and growth of the
      lesion. Patient demographic information, tumor characteristics, and histological
      data were collected from electronic medical records and paper charts. RESULTS:
      Out of 74 LGG patients, 10 patients (13.5%) were identified to meet the study
      criteria with number of MRIs acquired ranging from 8 to 18 (median, 11.5) over a
      median of 79.7 months (range 39.8-113.8 months). Tumor diameter increased at a
      median of 2.17 mm/year in a linear trajectory. Cox regression analysis revealed
      that initial tumor volume was an independent predictor of time to clinical
      intervention, and Mann-Whitney U test found that patients younger than 50 years
      old had significantly slower-growing tumors. Clinical intervention was more
      likely for tumors above a volume threshold of 73.6 mL. CONCLUSION: We
      retrospectively analyzed the natural history of LGGs of patients managed at a
      single institution with numerous serial MRI scans. Comparisons of our cohort to
      the literature suggest that this is a subset of particularly slow-growing and low
      risk tumors.

PMID- 29633112
TI  - A prospective phase II trial of response adapted whole brain radiotherapy after
      high dose methotrexate based chemotherapy in patients with newly diagnosed
      primary central nervous system lymphoma-analysis of acute toxicity profile and
      early clinical outcome.
AB  - BACKGROUND: The treatment of primary CNS lymphoma (PCNSL) comprises high dose
      methotrexate (HDMTX) based chemotherapy followed by whole brain radiotherapy
      (WBRT), the major drawback of which is long term neurotoxicity. We intended to
      assess the feasibility of response adapted WBRT in PCNSL in the Indian setting.
      METHODS: We screened 32 patients and enrolled 22 eligible patients with PCNSL
      from 2015 to 2017 in a prospective phase II trial. The patients underwent five 2
      weekly cycles of induction chemotherapy with rituximab, methotrexate,
      vincristine, procarbazine. Patients with complete response(CR) to induction
      chemotherapy were given reduced dose WBRT 23.4 Gy/13 fractions/2.5 weeks while
      those with partial response (PR), stable or progressive disease (SD or PD) were
      given standard dose WBRT 45 Gy/25 fractions/5 weeks. Thereafter two cycles of
      consolidation chemotherapy with cytarabine were given. The primary endpoints of
      the study were assessment of response rate (RR) and progression free survival
      (PFS). The secondary endpoints of the study were assessment of overall survival
      (OS), toxicity profile of treatment and serial changes in quality of life and
      neuropsychological parameters. RESULTS: Out of 19 patients who completed HDMTX
      based chemotherapy, 10 (52.63%) patients achieved CR, 8 (42.11%) patients had PR
      and 1 patient had PD. After a median follow-up period of 11.25 months, the
      estimated median OS was 19 months. The actuarial rates of PFS and OS were
      respectively 94.1 and 68.2% at 1 year and 50.2 and 48.5% at 2 years. Three
      patients in reduced dose WBRT arm had recurrence and two of them died of
      progressive disease, whereas there was no recurrence or disease related death in
      standard dose WBRT arm. On univariate analysis of PFS, age <= 50 years and use of
      standard dose WBRT (45 Gy) led to significantly improved outcome (p value 0.03
      and 0.02 respectively). CONCLUSION: In patients with PCNSL, reduced dose WBRT
      after CR to HDMTX based chemotherapy may lead to suboptimal clinical outcome due
      to higher risk of recurrence, progression and early death. Trial Registration No
      CTRI/2015/10/006268.

PMID- 29633113
TI  - Influence of the restorative procedure factors on stress values in premolar with
      MOD cavity: a finite element study.
AB  - In order to investigate the influence of cusp reduction, cavity isthmus width,
      and restorative material on stress values in premolar with mesio-occlusal-distal
      (MOD) cavity, numerical simulations were done on three-dimensional (3D) models of
      a maxillary second premolar designed using computerized tomography (CT) scan
      images. The use of four restorative materials (direct resin composite, direct
      resin composite with resin-modified glass-ionomer cement as the base, indirect
      resin composite, ceramic), three cavity preparation designs (without cusp
      coverage, 2-mm palatal cusp coverage, 2-mm palatal and buccal cusp coverage), and
      two cavity isthmus widths (1/2 and 2/3 intercuspal width) were simulated. After
      applying a static load of 200 N on the occlusal surface of the tooth, von Mises
      stresses in the enamel, dentin, and restoration were calculated using finite
      element analysis (FEA). Stress values in the enamel were primarily influenced by
      cavity preparation design, while restorative material showed higher contribution
      in dentin. The lowest stress values were obtained in models with cusp coverage
      and indirect restorations. Cavity isthmus width had minimal influence on stress
      values in tooth structures. None of the investigated factors determined stress
      values in the restoration. In conclusion, the use of ceramic restoration covering
      both palatal and buccal cusp provided the most favourable stress distribution of
      premolars with MOD cavity. Graphical abstract ?.

PMID- 29633115
TI  - Abdominal Aortic Blood Flow Disturbance Due to Binge Eating.

PMID- 29633114
TI  - The Prognostic Value of Varying Definitions of Positive Resection Margin in
      Patients with Colorectal Cancer Liver Metastases.
AB  - BACKGROUND: Varying definitions of resection margin clearance are currently
      employed among patients with colorectal cancer liver metastases (CRLM).
      Specifically, a microscopically positive margin (R1) has alternatively been
      equated with an involved margin (margin width = 0 mm) or a margin width < 1 mm.
      Consequently, patients with a margin width of 0-1 mm (sub-mm) are inconsistently
      classified in either the R0 or R1 categories, thus obscuring the prognostic
      implications of sub-mm margins. METHODS: Six hundred thirty-three patients who
      underwent resection of CRLM were identified. Both R1 definitions were
      alternatively employed and multivariable analysis was used to determine the
      predictive power of each definition, as well as the prognostic implications of a
      sub-mm margin. RESULTS: Five hundred thirty-nine (85.2%) patients had a margin
      width >= 1 mm, 42 had a sub-mm margin width, and 52 had an involved margin (0
      mm). A margin width >= 1 mm was associated with improved survival vs. a sub-mm
      margin (65 vs. 36 months; P = 0.03) or an involved margin (65 vs. 33 months; P <
      0.001). No significant difference in survival was detected between patients with
      involved vs. sub-mm margins (P = 0.31). A sub-mm margin and an involved margin
      were both independent predictors of worse OS (HR 1.66, 1.04-2.67; P = 0.04, and
      HR 2.14, 1.46-3.16; P < 0.001, respectively) in multivariable analysis.
      Importantly, after combining the two definitions, patients with either an
      involved margin or a sub-mm margin were associated with worse OS in multivariable
      analysis (HR 1.94, 1.41-2.65; P < 0.001). CONCLUSIONS: Patients with involved or
      sub-mm margins demonstrated a similar inferior OS vs. patients with a margin
      width > 1 mm. Consequently, a uniform definition of R1 as a margin width < 1 mm
      should perhaps be employed by future studies.

PMID- 29633117
TI  - Transmural Polypoid Endometriosis of the Sigmoid Colon.

PMID- 29633116
TI  - Superficial Surgical Site Infection in Hepatobiliary-Pancreatic Surgery:
      Subcuticular Suture Versus Skin Staples.
AB  - PURPOSE: Postoperative superficial surgical site infection is a major
      complication in hepatobiliary-pancreatic surgery. We aimed to compare the
      efficacy of subcuticular sutures versus staples for skin closure in preventing
      superficial surgical site infection in hepatobiliary-pancreatic surgery. METHODS:
      Consecutive patients who underwent hepatobiliary-pancreatic surgery at our
      hospital from October 2006 to March 2011 and from April 2012 to March 2015 were
      reviewed retrospectively. Superficial surgical site infection incidence was
      evaluated in patients who received subcuticular sutures and those who received
      staples for skin closure. Propensity score matching analysis was used to adjust
      bias from confounding factors. RESULTS: A total of 691 patients were included.
      Patients with skin staple closures (n = 346) were compared with patients with
      subcuticular suture closures (n = 345). After a propensity score matching
      analysis, a significant difference in superficial surgical site infection
      incidence was found between the skin stapler group (11.3%) and subcuticular
      sutures group (2.6%). The same comparison was performed by a subgroup analysis
      and supported this finding in patients after hepatectomy without biliary
      reconstruction, pancreatoduodenectomy, or open laparotomy surgeries and in
      patients with body mass index < 25. CONCLUSIONS: Subcuticular suturing after
      hepatobiliary-pancreatic surgery was more efficacious in reducing postoperative
      superficial surgical site infection incidence than staples for skin closure.

PMID- 29633118
TI  - Indocyanine Green Perfusion Imaging-Guided Laparoscopic Pancreaticoduodenectomy:
      Potential Application in Retroperitoneal Margin Dissection.
AB  - BACKGROUND: During laparoscopic pancreaticoduodenectomy (LPD), dissecting
      uncinate process from the superior mesenteric artery (SMA) will determine one of
      the important surgical margins (retroperitoneal margin) for predicting
      oncological outcomes and the quality of LPD. However, clear identification of the
      division line for retroperitoneal margin is not easy as the uncinate process of
      the pancreas is anatomically very close to SMA and intermingled with the nerve
      plexus and soft tissues around SMA. In this study, we present data regarding the
      potential usefulness of indocyanine green (ICG)-enhanced approach in obtaining
      retroperitoneal margin during LPD. METHODS: From January to September 2017,
      medical records of patients who underwent LPD for periampullary pathological
      conditions were retrospectively reviewed. ICG (5 mg/2 cm3) was prepared and
      intravenously injected when dissecting uncinate process of the pancreas.
      Perioperative outcomes, including gender, age, diagnosis, body mass index,
      operation time, estimated blood loss, transfusion, presence of postoperative
      pancreatic fistulas (POPFs), and length of hospital stay, were evaluated.
      RESULTS: During the study period, a total of 37 patients underwent LPD for
      periampullary pathological lesions. Among them, ICG-enhanced dissection of
      uncinate process of the pancreas was applied in 10 patients (27%). All patients
      were able to obtain margin-negative resection. There were no significant
      differences between the perioperative outcomes of patients who did and did not
      undergo ICG-enhanced approach. DISCUSSION: ICG perfusion-based laparoscopic
      dissection of retroperitoneal margin is feasible and safe in LPD. This
      intraoperative visual difference can provide the surgeon with very helpful real
      time visual information. Further study is mandatory.

PMID- 29633120
TI  - NaF Reduces KLK4 Gene Expression by Decreasing Foxo1 in LS8 Cells.
AB  - Decreased expression and increased phosphorylation of Forkhead box o1 (Foxo1) in
      ameloblasts were observed both in vivo and in vitro when treated by fluoride. The
      present study aims to investigate the possible relationship between Foxo1 and
      enamel matrix proteinases, matrix metalloproteinase 20 (MMP20), and kallikrein 4
      (KLK4), in NaF-treated ameloblasts. Ameloblast-like cells (LS8 cells) were
      exposed to NaF at selected concentration (0/2 mM) for 24 h. Gene overexpression
      and silencing experiments were used to up- and down-regulate Foxo1 expression.
      The expression levels of Foxo1, MMP20, and KLK4 were detected by quantitative
      real-time PCR and western blot. Dual luciferase reporter assay was performed to
      evaluate the regulation of Foxo1 on the transcriptional activity of KLK4
      promoter. The results showed that KLK4 expression was decreased in LS8 cells
      treated by NaF, while MMP20 expression was not changed. Foxo1 activation led to
      significantly up-regulation of KLK4 in LS8 cells under NaF condition. Knockout of
      Foxo1 markedly decreased klk4 expression in mRNA level, and intensified
      inhibition occurred in LS8 cells when combined with NaF treatment. However, the
      variation trend of MMP20 was not clear. Dual luciferase reporter assay showed
      that Foxo1 activation enhanced the transcriptional activity of KLK4 promoter.
      These findings suggest that the decrease of Foxo1 expression induced by high
      fluoride was a cause for low KLK4 expression.

PMID- 29633121
TI  - Cushing syndrome due to adrenal carcinoma.

PMID- 29633119
TI  - The New Frontier: the Intestinal Microbiome and Surgery.
AB  - The microbiome exerts a remarkable effect on human physiology. The study of the
      human-microbiome relationship is a burgeoning field with great potential to
      improve our understanding of health and disease. In this review, we address
      common surgical problems influenced by the human microbiome and explore what is
      thus far known about this relationship. These include inflammatory bowel disease,
      colorectal neoplasms, and diverticular disease. We will also discuss the effect
      of the microbiome on surgical complications, specifically anastomotic leak. We
      hope that further research in this field will enlighten our management of these
      and other surgical problems.

PMID- 29633122
TI  - Use of Stakeholder Focus Groups to Define the Mission and Scope of a new
      Department of Population Health.
AB  - BACKGROUND: The focus and funding of US healthcare is evolving from volume to
      value-based, and healthcare leaders, managers, payers, and researchers are
      increasingly focusing on managing populations of patients. Simultaneously, there
      is increasing interest in getting "upstream" from disease management to promote
      health and prevent disease. Hence, the term "population health" has both clinical
      and community-based connotations relevant to the tripartite mission of US medical
      schools. OBJECTIVE: To seek broad input for the strategic development of the
      Department of Population Health in a new medical school at a tier 1 research
      university. DESIGN: Focus groups with facilitated consensus development.
      PARTICIPANTS: Eighty-one persons representing the Dell Medical School and other
      schools at the University of Texas at Austin, city/county government, community
      nonprofit organizations, and faculty from other local university schools along
      with selected national academic leaders. APPROACH: Focus groups with subsequent
      consensus development of emphases identified premeeting by participants by e-mail
      exchanges. KEY RESULTS: The resulting departmental strategic plan included scope
      of work, desired characteristics of leaders, and early impact activities in seven
      areas of interest: community engagement and health equity, primary care and value
      based health, occupational and environment medicine, medical education, health
      services and community-based research, health informatics and data analysis, and
      global health. CONCLUSIONS: Medical schools should have a primary focus in
      population, most effectively at the departmental level. Engaging relevant
      academic and community stakeholders is an effective model for developing this
      emerging discipline in US medical schools.

PMID- 29633123
TI  - Care Coordination Management in Patient-Centered Medical Home: Analysis of the
      2015 Medical Organizations Survey.

PMID- 29633124
TI  - Effectiveness of Intensive Primary Care.

PMID- 29633125
TI  - Capsule Commentary on Navathe, et al., Do Changes in Post-acute Care Use at
      Hospitals Participating in an Accountable Care Organization Spillover to all
      Medicare Beneficiaries?

PMID- 29633126
TI  - Capsule Commentary on Njeru et al., Diabetes Mellitus Management Among Patients
      with Limited English Proficiency: a Systematic Review and Meta-analysis.

PMID- 29633127
TI  - Patient as Co-Teacher on Rounds: a Pilot Study.

PMID- 29633128
TI  - Cor Triatriatum as an Uncommon Cause of Recurrent Syncope.

PMID- 29633129
TI  - Analysis of the Variability of Abstract Structures in Medical Journals.

PMID- 29633130
TI  - Clinician Referrals for Non-opioid Pain Care Following Discontinuation of Long
      term Opioid Therapy Differ Based on Reasons for Discontinuation.
AB  - BACKGROUND: Little is known about pain care offered to patients discontinued from
      long-term opioid therapy (LTOT) by their prescriber due to aberrant behaviors
      versus other reasons. OBJECTIVE: This study aimed to compare rates of non-opioid
      analgesic pharmacotherapy initiation and clinician referrals for non
      pharmacologic pain treatment, complementary and integrative pain therapies, and
      specialty mental health and substance use disorder treatment between patients
      discontinued from opioid therapy due to aberrant behaviors versus other reasons.
      DESIGN: The design included retrospective manual electronic health record review
      and administrative data abstraction. PARTICIPANTS: Patients were sampled from a
      national cohort of US Department of Veterans Affairs patients prescribed
      continuous opioid therapy in 2011 who subsequently discontinued opioid therapy in
      2012. The study sample comprised 509 patients discontinued from LTOT by opioid
      prescribing clinicians. MAIN MEASURES: The primary independent variable was
      reason for discontinuation of LTOT (aberrant behaviors versus other reasons).
      Pain care dichotomous outcomes included clinician use of an opioid taper;
      initiating new non-opioid analgesic pharmacotherapy; and referrals for non
      pharmacologic pain treatment, complementary and integrative pain therapies, and
      specialty mental health and substance use disorder treatment. KEY RESULTS: We
      observed low rates of opioid taper (15% of patients), initiations of new or
      modifications of existing non-opioid analgesic pharmacotherapy (45% of patients),
      and clinician referrals for non-pharmacologic pain treatment (58% of patients)
      and complementary and integrative therapies (25% of patients). Patients
      discontinued due to aberrant behaviors, relative to patients discontinued for
      other reasons, were more likely to receive opioid tapers (adjusted OR = 5.60, 95%
      CI = 2.10-14.93), receive new non-opioid analgesic medications or dose changes to
      an existing non-opioid analgesic medications (adjusted OR = 2.61, 95% CI = 1.59
      4.29), or be referred for specialty substance use disorder treatment (adjusted OR
      = 7.39, 95% CI = 3.76-14.53). CONCLUSIONS: These findings highlight the
      variability in referral rates for different types of non-opioid pain treatments
      and challenges accessing specific types of pain care.

PMID- 29633131
TI  - Making Integrated Multimodal Pain Care a Reality: A Path Forward.

PMID- 29633132
TI  - How Can the Intractable Problem of Chronic Musculoskeletal Pain (CMP) Be
      Effectively Managed? The Need for a Well-Integrated Systems Approach.

PMID- 29633134
TI  - For the Relief of Suffering.

PMID- 29633133
TI  - Clinical Policy Recommendations from the VHA State-of-the-Art Conference on Non
      Pharmacological Approaches to Chronic Musculoskeletal Pain.
AB  - As a large national healthcare system, Veterans Health Administration (VHA) is
      ideally suited to build on its work to date and develop a safe, evidence-based,
      and comprehensive approach to the care of chronic musculoskeletal pain conditions
      that de-emphasizes opioid use and emphasizes non-pharmacological strategies. The
      VHA Office of Health Services Research and Development (HSR&D) held a state-of
      the-art (SOTA) conference titled "Non-pharmacological Approaches to Chronic
      Musculoskeletal Pain Management" in November 2016. Goals of the conference were
      (1) to establish consensus on the current state of evidence regarding non
      pharmacological approaches to chronic musculoskeletal pain to inform VHA policy
      in this area and (2) to begin to identify priorities for the future VHA research
      agenda. Workgroups were established and asked to reach consensus recommendations
      on clinical and research priorities for the following treatment strategies:
      psychological/behavioral therapies, exercise/movement therapies, manual
      therapies, and models for delivering multimodal pain care. Participants in the
      SOTA identified nine non-pharmacological therapies with sufficient evidence to be
      implemented across the VHA system as part of pain care. Participants further
      recommended that effective integration of these non-pharmacological approaches
      across the VHA and especially into VHA primary care, pain care, and mental health
      settings should be a priority, and that these treatments should be offered early
      in the course of pain treatment and delivered in a team-based, multimodal
      treatment setting concurrently with active self-care and self-management
      approaches. In addition, we recommend that VHA leadership and policy makers
      systematically address the barriers to implementation of these approaches by
      expanding opportunities for clinician and veteran education on the effectiveness
      of these strategies; supporting and funding further research to determine optimal
      dosage, duration, sequencing, combination, and frequency of treatment;
      emphasizing multimodal care with rigorous evaluation grounded in team-based
      approaches to test integrated models of delivery and stepped-care approaches; and
      working to address socioeconomic and cultural barriers to veterans' access to non
      pharmacological approaches.

PMID- 29633135
TI  - Pain measurement in research and practice.

PMID- 29633136
TI  - A Research Agenda for Advancing Non-pharmacological Management of Chronic
      Musculoskeletal Pain: Findings from a VHA State-of-the-art Conference.
AB  - Chronic pain is widely prevalent among Veterans and can have serious negative
      consequences for functional status and quality of life among other domains. The
      Veterans Health Administration (VHA) convened a state-of-the-art (SOTA)
      conference to develop research priorities for advancing the science and clinical
      practice of non-pharmacological management of chronic musculoskeletal pain. In
      this perspective article, we present the methods and consensus recommendations
      for research priorities emanating from the SOTA. In the months leading up to the
      SOTA, a core group of researchers defined four areas of focus:
      psychological/behavioral therapies; exercise/movement therapies; manual
      therapies; and models for delivering multi-modal pain care and divided into
      workgroups. Each workgroup, in their respective areas of focus, identified
      seminal studies capturing the state of the evidence. Herein, we present consensus
      recommendations ranging from efficacy to effectiveness to
      implementation/dissemination research depending on the state of the evidence as
      assessed by participants, including commentary on common elements across
      workgroups and future areas of innovation in study design, measurement, and
      outcome ascertainment.

PMID- 29633137
TI  - Association Between Facility-Level Utilization of Non-pharmacologic Chronic Pain
      Treatment and Subsequent Initiation of Long-Term Opioid Therapy.
AB  - BACKGROUND: Expert guidelines recommend non-pharmacologic treatments and non
      opioid medications for chronic pain and recommend against initiating long-term
      opioid therapy (LTOT). OBJECTIVE: We examined whether veterans with incident
      chronic pain receiving care at facilities with greater utilization of non
      pharmacologic treatments and non-opioid medications are less likely to initiate
      LTOT. DESIGN: Retrospective cohort study PARTICIPANTS: Veterans receiving primary
      care from a Veterans Health Administration facility with incident chronic pain
      between 1/1/2010 and 12/31/2015 based on either of 2 criteria: (1) persistent
      moderate-to-severe patient-reported pain and (2) diagnoses "likely to represent"
      chronic pain. MAIN MEASURES: The independent variable was facility-level
      utilization of pain-related treatment modalities (non-pharmacologic, non-opioid
      medications, LTOT) in the prior calendar year. The dependent variable was patient
      level initiation of LTOT (>= 90 days within 365 days) in the subsequent year,
      adjusting for patient characteristics. KEY RESULTS: Among 1,094,569 veterans with
      incident chronic pain from 2010 to 2015, there was wide facility-level variation
      in utilization of 10 pain-related treatment modalities, including initiation of
      LTOT (median, 16%; range, 5-32%). Veterans receiving care at facilities with
      greater utilization of non-pharmacologic treatments were less likely to initiate
      LTOT in the year following incident chronic pain. Conversely, veterans receiving
      care at facilities with greater non-opioid and opioid medication utilization were
      more likely to initiate LTOT; this association was strongest for past year
      facility-level LTOT initiation (adjusted rate ratio, 2.10; 95% confidence
      interval, 2.06-2.15, top vs. bottom quartile of facility-level LTOT initiation in
      prior calendar year). CONCLUSIONS: Facility-level utilization patterns of non
      pharmacologic, non-opioid, and opioid treatments for chronic pain are associated
      with subsequent patient-level initiation of LTOT among veterans with incident
      chronic pain. Further studies should seek to understand facility-level variation
      in chronic pain care and to identify facility-level utilization patterns that are
      associated with improved patient outcomes.

PMID- 29633138
TI  - Correlates of Use and Perceived Effectiveness of Non-pharmacologic Strategies for
      Chronic Pain Among Patients Prescribed Long-term Opioid Therapy.
AB  - OBJECTIVE: Non-pharmacologic treatments (NPTs) are recommended for chronic pain.
      Information is limited on patient use or perceptions of NPTs. We examined the
      frequency and correlates of use and self-rated helpfulness of NPTs for chronic
      pain among patients who are prescribed long-term opioid therapy (LTOT). METHODS:
      Participants (n = 517) with musculoskeletal pain who were prescribed LTOT were
      recruited from two integrated health systems. They rated the frequency and
      utility of six clinician-directed and five self-directed NPTs for chronic pain.
      We categorized NPT use at four levels based on number of interventions used and
      frequency of use (none, low, moderate, high). Analyses examined clinical and
      demographic factors that differed among groups for both clinician-directed and
      self-directed NPTs. RESULTS: Seventy-one percent of participants reported use of
      any NPT for pain within the prior 6 months. NPTs were rated as being helpful by
      more than 50% of users for all treatments assessed (range 51-79%). High users of
      clinician-directed NPTs were younger than non-users or low-frequency users and
      had the most depressive symptoms. In both clinician-directed and self-directed
      categories, high NPT users had significantly higher pain disability compared to
      non-NPT users. No significant group differences were detected on other
      demographic or clinical variables. In multivariable analyses, clinician-directed
      NPT use was modestly associated with younger age (OR = 0.97, 95% CI = 0.96-0.98)
      and higher pain disability (OR = 1.01, 95% CI = 1.00-1.02). Variables associated
      with greater self-directed NPT use were some college education (OR = 1.80, 95% CI
      = 1.13-2.84), college graduate or more (OR = 2.02, 95% CI = 1.20-3.40), and
      higher pain disability (OR = 1.01, 95% CI = 1.01-1.02). CONCLUSIONS: NPT use was
      associated with higher pain disability and younger age for both clinician
      directed and self-directed NPTs and higher education for self-directed NPTs.
      These strategies were rated as helpful by those that used them. These results can
      inform intervention implementation and be used to increase engagement in NPTs for
      chronic pain.

PMID- 29633139
TI  - Automating Collection of Pain-Related Patient-Reported Outcomes to Enhance
      Clinical Care and Research.
AB  - INTRODUCTION: Chronic pain is highly prevalent, and the ability to routinely
      measure patients' pain and treatment response using validated patient-reported
      outcome (PRO) assessments is important to clinical care. Despite this
      recognition, systematic use in everyday clinical care is rare. AIMS: The aims of
      this study were to (1) describe infrastructure designed to automate PRO data
      collection, (2) compare study-enhanced PRO completion rates to those in clinical
      care, and (3) evaluate patient response rates by method of PRO administration and
      sociodemographic and/or clinical characteristics. SETTING: The Pain Program for
      Active Coping and Training (PPACT) is a pragmatic clinical trial conducted within
      three regions of the Kaiser Permanente health care system. PROGRAM DESCRIPTION:
      PPACT evaluates the effect of integrative primary care-based pain management
      services on outcomes for chronic pain patients on long-term opioid treatment. We
      implemented a tiered process for quarterly assessment of PROs to supplement
      clinical collection and ensure adequate trial data using three methods: web-based
      personal health records (PHR), automated interactive voice response (IVR) calls,
      and live outreach. PROGRAM EVALUATION: Among a subset of PPACT participants
      examined (n = 632), the tiered study-enhanced PRO completion rates were higher
      than in clinical care: 96% completed >= 1 study-administered PRO with mean of
      3.46 (SD = 0.85) vs. 74% completed in clinical care with a mean of 2.43 (SD =
      2.08). Among all PPACT participants at 3 months (n = 831), PRO completion was 86%
      and analyses of response by key characteristics found only that participant age
      predicted an increased likelihood of responding to PHR and IVR outreach.
      DISCUSSION: Adherence to pain-related PRO data collection using our enhanced
      tiered approach was high. No demographic or clinical identifiers other than age
      were associated with differential response by modality. Successful ancillary
      support should employ multimodal electronic health record functionalities for PRO
      administration. Using automated modalities is feasible and may facilitate better
      sustainability for regular PRO administration within health care systems.
      Clinical Trials Registration Number: NCT02113592.

PMID- 29633140
TI  - Effectiveness of Models Used to Deliver Multimodal Care for Chronic
      Musculoskeletal Pain: a Rapid Evidence Review.
AB  - BACKGROUND: Primary care providers (PCPs) face many system- and patient-level
      challenges in providing multimodal care for patients with complex chronic pain as
      recommended in some pain management guidelines. Several models have been
      developed to improve the delivery of multimodal chronic pain care. These models
      vary in their key components, and work is needed to identify which have the
      strongest evidence of clinically-important improvements in pain and function. Our
      objective was to determine which primary care-based multimodal chronic pain care
      models provide clinically relevant benefits, define key elements of these models,
      and identify patients who are most likely to benefit. METHODS: To identify
      studies, we searched MEDLINE(r) (1996 to October 2016), CINAHL, reference lists,
      and numerous other sources and consulted with experts. We used predefined
      criteria for study selection, data abstraction, internal validity assessment, and
      strength of evidence grading. RESULTS: We identified nine models, evaluated in
      mostly randomized controlled trials (RCTs). The RCTs included 3816 individuals
      primarily from the USA. The most common pain location was the back. Five models
      primarily coupling a decision-support component-most commonly algorithm-guided
      treatment and/or stepped care-with proactive ongoing treatment monitoring have
      the best evidence of providing clinically relevant improvement in pain intensity
      and pain-related function over 9 to 12 months (NNT range, 4 to 13) and variable
      improvement in quality of life, depression, anxiety, and sleep. The strength of
      the evidence was generally low, as each model was only supported by a single RCT
      with imprecise findings. DISCUSSION: Multimodal chronic pain care delivery models
      coupling decision support with proactive treatment monitoring consistently
      provide clinically relevant improvement in pain and function. Wider
      implementation of these models should be accompanied by further evaluation of
      clinical and implementation effectiveness.

PMID- 29633141
TI  - Use of Non-Pharmacological Pain Treatment Modalities Among Veterans with Chronic
      Pain: Results from a Cross-Sectional Survey.
AB  - BACKGROUND: Despite strong evidence for the effectiveness of non-pharmacological
      pain treatment modalities (NPMs), little is known about the prevalence or
      correlates of NPM use. OBJECTIVE: This study examined rates and correlates of NPM
      use in a sample of veterans who served during recent conflicts. DESIGN: We
      examined rates and demographic and clinical correlates of self-reported NPM use
      (operationalized as psychological/behavioral therapies, exercise/movement
      therapies, and manual therapies). We calculated descriptive statistics and
      examined bivariate associations and multivariable associations using logistic
      regression. PARTICIPANTS: Participants were 460 veterans endorsing pain lasting
      >= 3 months who completed the baseline survey of the Women Veterans Cohort Study
      (response rate 7.7%. MAIN MEASURES: Outcome was self-reported use of NPMs in the
      past 12 months. KEY RESULTS: Veterans were 33.76 years old (SD = 10.72), 56.3%
      female, and 80.2% White. Regarding NPM use, 22.6% reported using
      psychological/behavioral, 50.9% used exercise/movement and 51.7% used manual
      therapies. Veterans with a college degree (vs. no degree; OR = 2.51, 95% CI =
      1.46, 4.30, p = 0.001) or those with worse mental health symptoms (OR = 2.88, 95%
      CI = 2.11, 3.93, p < 0.001) were more likely to use psychological/behavioral
      therapies. Veterans who were female (OR = 0.63, 95% CI = 0.43, 0.93, p = 0.02) or
      who used non-opioid pain medications (OR = 1.82, 95% CI = 1.146, 2.84, p = 0.009)
      were more likely to use exercise/movement therapies. Veterans who were non-White
      (OR = 0.57, 95% CI = 0.5, 0.94, p = 0.03), with greater educational attainment
      (OR = 2.11, 95% CI = 1.42, 3.15, p < 0.001), or who used non-opioid pain
      medication (OR = 1.71, 95% CI = 1.09, 2.68, p = 0.02) were more likely to use
      manual therapies. CONCLUSIONS: Results identified demographic and clinical
      characteristics among different NPMs, which may indicate differences in veteran
      treatment preferences or provider referral patterns. Further study of provider
      referral patterns and veteran treatment preferences is needed to inform
      interventions to increase NPM utilization. Research is also need to identify
      demographic and clinical correlates of clinical outcomes related to NPM use.

PMID- 29633142
TI  - Focused Evidence Review: Psychometric Properties of Patient-Reported Outcome
      Measures for Chronic Musculoskeletal Pain.
AB  - BACKGROUND: Developing successful interventions for chronic musculoskeletal pain
      requires valid, responsive, and reliable outcome measures. The Minneapolis VA
      Evidence-based Synthesis Program completed a focused evidence review on key
      psychometric properties of 17 self-report measures of pain severity and pain
      related functional impairment suitable for clinical research on chronic
      musculoskeletal pain. METHODS: Pain experts of the VA Pain Measurement Outcomes
      Workgroup identified 17 pain measures to undergo systematic review. In addition
      to a MEDLINE search on these 17 measures (1/2000-1/2017), we hand-searched
      (without publication date limits) the reference lists of all included studies,
      prior systematic reviews, and-when available-Web sites dedicated to each measure
      (PROSPERO registration CRD42017056610). Our primary outcome was the measure's
      minimal important difference (MID). Secondary outcomes included responsiveness,
      validity, and test-retest reliability. Outcomes were synthesized through evidence
      mapping and qualitative comparison. RESULTS: Of 1635 abstracts identified, 331
      articles underwent full-text review, and 43 met inclusion criteria. Five measures
      (Oswestry Disability Index (ODI), Roland-Morris Disability Questionnaire (RMDQ),
      SF-36 Bodily Pain Scale (SF-36 BPS), Numeric Rating Scale (NRS), and Visual
      Analog Scale (VAS)) had data reported on MID, responsiveness, validity, and test
      retest reliability. Seven measures had data reported on three of the four
      psychometric outcomes. Eight measures had reported MIDs, though estimation
      methods differed substantially and often were not clinically anchored.
      CONCLUSIONS: In this focused evidence review, the most evidence on key
      psychometric properties in chronic musculoskeletal pain populations was found for
      the ODI, RMDQ, SF-36 BPS, NRS, and VAS. Key limitations in the field include
      substantial variation in methods of estimating psychometric properties, defining
      chronic musculoskeletal pain, and reporting patient demographics. TRIAL
      REGISTRATION: Registered in the PROSPERO database: CRD42017056610.

PMID- 29633143
TI  - Tracking Steps on Apple Watch at Different Walking Speeds.
AB  - KEY POINTS: QUESTION: How accurate are the step counts obtained from Apple Watch?
      FINDINGS: In this validation study, video steps vs. Apple Watch steps (mean +/-
      SD) were 2965 +/- 144 vs. 2964 +/- 145 steps; P < 0.001. Lin's concordance
      correlation coefficient showed a strong correlation (r = 0.96; P < 0.001) between
      the two measurements. There was a total error of 0.034% (1.07 steps) for the
      Apple Watch steps when compared with the manual counts obtained from video
      recordings. MEANING: Our study is one of the initial studies to objectively
      validate the accuracy of the step counts obtained from Apple watch at different
      walking speeds. Apple Watch tested to be an extremely accurate device for
      measuring daily step counts for adults.

PMID- 29633144
TI  - A score derived from routine biochemical parameters increases the diagnostic
      accuracy of chromogranin A in detecting patients with neuroendocrine neoplasms.
AB  - BACKGROUND: Chromogranin A (CgA) is a valuable biomarker for detection and follow
      up of patients with neuroendocrine neoplasms (NENs). However, various
      comorbidities may influence serum CgA, which decreases its diagnostic accuracy.
      We aimed to investigate which laboratory parameters are independently associated
      with increased CgA in real-life setting and to develop a scoring system, which
      could improve the diagnostic accuracy of CgA in detecting patients with NENs.
      METHODS: This retrospective study included 55 treatment naive patients with NENs
      and160 patients with various comorbidities but without NEN (nonNENs). Scoring
      system (CgA-score) was developed based on z-scores obtained from receiver
      operating curve analysis for each parameter that was associated with elevated
      serum CgA in nonNENs. RESULTS: CgA correlated positively with serum BUN,
      creatinine, alpha2-globulin, red-cell distribution width, erythrocyte
      sedimentation rate, plasma glucose and correlated inversely with hemoglobin,
      thrombocytes and serum albumin. Serum CgA was also associated with the presence
      of chronic renal failure, arterial hypertension and diabetes and the use of PPI.
      In the entire study population, CgA showed an area under the curve of 0.656.
      Aforementioned parameters were used to develop a CgA-score. In a cohort of
      patients with CgA-score <12.0 (N = 87), serum CgA >156.5 ng/ml had 77.8%
      sensitivity and 91.5% specificity for detecting NENs (AUC 0.841, 95% CI 0.713
      0.969, P < 0.001). Serum CgA had no diagnostic value in detecting NENs in
      patients with CgA-score >12.0 (AUC 0.554, 95% CI 0.405-0.702, P = 0.430).
      CONCLUSIONS: CgA-score encompasses a wide range of comorbidities and represents a
      promising tool that could improve diagnostic performance of CgA in everyday
      clinical practice.

PMID- 29633145
TI  - On the confluence of reproductive and regenerative medicines.

PMID- 29633146
TI  - Sequential clomiphene/corifollitrophin alpha as a technique for mild controlled
      ovarian hyperstimulation in IVF: a proof of concept study.
AB  - PURPOSE: Mild controlled ovarian hyperstimulation (COH), combined with oocyte
      retrieval (OR) under local anaesthesia (LA), may provide low-impact IVF. Since a
      single injection of corifollitrophin alfa (CFA) provides 7 days of COH, we
      hypothesised that clomiphene-citrate (CC) followed by CFA may provide adequate
      COH response from one single FSH injection. Therefore, the aim was to assess IVF
      outcomes after a novel clomiphene citrate/CFA (CC/CFA) protocol, compared to
      women undergoing standard rFSH COH protocols (good prognosis comparative
      cohort:GPCC) in a 1:2 matched design. MATERIALS AND METHODS: In this pilot study
      of 25 patients (ANZCTR id:ACTRN12612000740897,
      MINIVA:Minimal_Stimulation_in_IVF), we examined the effectiveness of oral
      clomiphene (100 mg-days 2-6) followed by CFA in a GnRH antagonist protocol
      producing a single injection COH stimulation regime. All OR were conducted under
      LA pre-ovarian block. Cycle outcomes were compared to a matched good prognosis
      comparative cohort (GPCC) undergoing standard rFSH COH. RESULTS: Mild stimulation
      was achieved with less oocytes being collected compared to the GPCC (6.4 +/- 0.7
      vs. 10.7 +/- 0.9, p < 0.001), resulting in a reduced number of good quality
      embryos available for transfer/cryopreservation (3.7 +/- 0.6 vs. 5.7 +/- 0.5, p =
      0.01). While embryo quality was similar between the two groups, endometrial
      thickness was significantly lower in the group receiving CC/CFA. Pregnancy rates
      were significantly lower in the CC/CFA cohort compared to GPCC (31.8 vs. 57.1%, p
      = 0.04) and 44% of CC/CFA participants required supplemental rFSH in order to
      achieve the hCG trigger criteria. CONCLUSION: Sequential clomiphene CFA protocol
      does not appear to be an optimal regime for low impact IVF treatment as it does
      not provide adequate COH from a single CFA injection and results in lower fresh
      embryo transfer pregnancy rates and fewer embryos for cryopreservation.

PMID- 29633147
TI  - Mode of conception does not affect fetal or placental growth parameters or ratios
      in early gestation or at delivery.
AB  - PURPOSE: Ratio of fetal weight to placenta size varies by mode of conception
      (fertility treatments utilized) in animals. Our objective was to assess whether
      fertility treatments also affect these ratios in humans. METHODS: In this
      retrospective study, we assessed two cohorts: (a) early gestation cohort, women
      with singleton pregnancies who underwent first trimester vaginal ultrasound and
      (b) delivered cohort, women who delivered a live-born, singleton infant with
      placenta disposition to pathology. Crown rump length (CRL) and estimated
      placental volume (EPV) were calculated from first trimester ultrasound images
      using a validated computation. Infant birth weight (BW), pregnancy data,
      placental weight (PW), and placental histopathology were collected. Fetal growth
      to-placental weight ratios (CRL/EPV; BW/PW) and placentas were compared by mode
      of conception. Linear regression was used to adjust for confounding variables.
      RESULTS: Two thousand one hundred seventy patients were included in the early
      gestation cohort and 1443 in the delivered cohort. Of the early gestation cohort
      (a), 85.4% were spontaneous conceptions, 5.9% Non-IVF Fertility (NIFT), and 8.7%
      IVF. In the delivered cohort (b), 92.4% were spontaneous, 2.1% NIFT, and 80 5.5%
      IVF. There were no significant differences between fetal growth-to-placental
      weight parameters, ratios, and neonatal birth measurements based on mode of
      conception. Placenta accreta was significantly higher in the patients receiving
      fertility treatments (1.2 versus 3.6%, p < 0.05). CONCLUSIONS: Mode of conception
      does not appear to influence fetal growth-to-placental weight ratios throughout
      gestation. In addition, findings in animal models may not always translate into
      human studies of infertility treatment outcomes.

PMID- 29633148
TI  - Birthweight in infants conceived through in vitro fertilization following
      blastocyst or cleavage-stage embryo transfer: a national registry study.
AB  - PURPOSE: In vitro fertilization (IVF) infants have lower birthweights than their
      peers, predisposing them to long-term health consequences. Blastocyst transfer
      (BT), at day 5-6 post-fertilization, is increasing in usage, partially due to
      improved pregnancy outcomes over cleavage-stage transfer (CT, day 2-3). Data to
      date, however, have been inconclusive regarding BT's effects on birthweight.
      METHODS: Participants included all US autologous, single-gestation, fresh embryo
      transfer cycles initiated from 2007 to 2014 that resulted in a term infant (N =
      124,154) from the National Assisted Reproductive Technology Surveillance System.
      Generalized linear models including obstetric history, maternal demographics, and
      infant sex and gestational age were used to compare birthweight outcomes for
      infants born following BT (N = 67,169) with infants born following CT (N =
      56,985) and to test for an interaction between transfer stage and single embryo
      transfer (SET). RESULTS: Infants born following BT were 6 g larger than those
      born following CT (p = 0.04), but rates of macrosomia (RR 1.00, 95% CI 0.96-1.04)
      and low birthweight (LBW, RR 1.00, 95% CI 0.93-1.06) were not different between
      the groups. The interaction between SET and transfer stage was significant (p =
      0.02). Among SET infants, BT was associated with 19.26 g increased birthweight
      compared to CT (p = 0.008). CONCLUSIONS: The increase in birthweights identified
      following BT is unlikely to be clinically relevant, as there were no differences
      in rates of macrosomia or LBW. These findings are clinically reassuring and
      indicate that the increasing use of BT is unlikely to further decrease the on
      average lower birthweights seen in IVF infants compared to their naturally
      conceived peers.

PMID- 29633149
TI  - Human nail stem cells are retained but hypofunctional during aging.
AB  - The nail is a continuous skin appendage. Cells located around the nails, which
      display coordinated homeostatic dynamics and release a flow of stem cells in
      response to regeneration, have been identified in mice. However, very few studies
      regarding human nail stem cells exist in the literature. Using specimens isolated
      from humans, we detected an unreported population of cells within the basal layer
      of postnatal human nail proximal folds (NPFs) and the nail matrix around the nail
      root. These cells were multi-expressing and expressed stem cell markers, such as
      keratin 15 (K15), keratin 14 (K14), keratin 19 (K19), CD29, CD34, and leucine
      rich repeat-containing G protein-coupled receptor 6 (Lgr6). These cells were very
      similar to mouse nail stem cells in terms of cell marker expression and their
      location within the nail. We also found that the putative nail stem cells
      maintained their abundance with advancing age, but cell proliferation and nail
      growth rate were decreased on comparison of young and aged specimens. To
      summarize, we found a putative population of stem cells in postnatal human nails
      located at NPFs and the nail matrix. These cells may have potential for cell
      differentiation and be capable of responding to injury, and were retained, but
      may be hypofunctional during aging.

PMID- 29633150
TI  - Genetics of personalized medicine: cancer and rare diseases.
AB  - The 21st annual meeting of the Portuguese Society of Human Genetics (SPGH),
      organized by Luisa Romao, Ana Sousa and Rosario Pinto Leite, was held in
      Caparica, Portugal, from the 16th to the 18th of November 2017. Having entered an
      era in which personalized medicine is emerging as a paradigm for disease
      diagnosis, treatment and prevention, the program of this meeting intended to
      include lectures by leading national and international scientists presenting
      exceptional findings on the genetics of personalized medicine. Various topics
      were discussed, including cancer genetics, transcriptome dynamics and novel
      therapeutics for cancers and rare disorders that are designed to specifically
      target molecular alterations in individual patients. Several panel discussions
      were held to emphasize (ethical) issues associated with personalized medicine,
      including genetic cancer counseling.

PMID- 29633151
TI  - A Delphi Consensus of the Crucial Steps in Gastric Bypass and Sleeve Gastrectomy
      Procedures in the Netherlands.
AB  - PURPOSE: Bariatric procedures are technically complex and skill demanding. In
      order to standardize the procedures for research and training, a Delphi analysis
      was performed to reach consensus on the practice of the laparoscopic gastric
      bypass and sleeve gastrectomy in the Netherlands. METHODS: After a pre-round
      identifying all possible steps from literature and expert opinion within our
      study group, questionnaires were send to 68 registered Dutch bariatric surgeons,
      with 73 steps for bypass surgery and 51 steps for sleeve gastrectomy. Statistical
      analysis was performed to identify steps with and without consensus. This process
      was repeated to reach consensus of all necessary steps. RESULTS: Thirty-eight
      participants (56%) responded in the first round and 32 participants (47%) in the
      second round. After the first Delphi round, 19 steps for gastric bypass (26%) and
      14 for sleeve gastrectomy (27%) gained full consensus. After the second round, an
      additional amount of 10 and 12 sub-steps was confirmed as key steps,
      respectively. Thirteen steps in the gastric bypass and seven in the gastric
      sleeve were deemed advisable. Our expert panel showed a high level of consensus
      expressed in a Cronbach's alpha of 0.82 for the gastric bypass and 0.87 for the
      sleeve gastrectomy. CONCLUSIONS: The Delphi consensus defined 29 steps for
      gastric bypass and 26 for sleeve gastrectomy as being crucial for correct
      performance of these procedures to the standards of our expert panel. These
      results offer a clear framework for the technical execution of these procedures.

PMID- 29633152
TI  - Anemia and Bariatric Surgery: Results of a National French Survey on
      Administrative Data of 306,298 Consecutive Patients Between 2008 and 2016 :
      Bailly L, Schiavo L, Sebastianelli L, Fabre R, Pradier C, Iannelli A. Obes Surg.
      2018 Mar 7. doi: 10.1007/s11695-018-3143-x. [Epub ahead of print].

PMID- 29633153
TI  - Anaemia After One Anastomosis Gastric Bypass.

PMID- 29633154
TI  - Two Contrasting Failure Modes of Enteric Coated Beads.
AB  - This study aimed to elucidate the mechanisms and kinetics of coating failure for
      enteric coated beads exposed to high-humidity conditions at different storage
      temperatures. Enteric coated beads were placed on high-humidity conditions (75 to
      98% relative humidity (RH)) in the temperature range of 5 to 40 degrees C. These
      stability samples of beads were tested for acid dissolution and water activity
      and also analyzed with SEM, X-ray CT, and DMA. Exposure of enteric coated beads
      to high humidity led to increased gastric release of drug which eventually failed
      the dissolution specification. SEM showed visible cracks on the surface of beads
      exposed to 5 degrees C/high humidity and fusion of enteric beads into
      agglomerates at 40 degrees C/high humidity. In a non-destructive time elapse
      study, X-ray CT demonstrated swelling of microcrystalline cellulose cores, crack
      initiation, and propagation through the API layer within days under 5 degrees
      C/98% RH storage conditions and ultimately fracture through the enteric coating.
      DMA data showed a marked reduction in Tg of the enteric coating materials after
      exposure to humidity. At 5 degrees C/high humidity, the hygroscopic
      microcrystalline cellulose core absorbed moisture leading to core swelling and
      consequent fracture through the brittle API and enteric layers. At 40 degrees C
      (high humidity) which is above the Tg of the enteric polymer, enteric coated
      beads coalesced into agglomerates due to melt flow of the enteric coating. We
      believe it is the first report on two distinct failure models of enteric coated
      dosage forms.

PMID- 29633155
TI  - Magnetic Resonance Imaging in Aneurysmal Subarachnoid Hemorrhage: Current
      Evidence and Future Directions.
AB  - BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is associated with an
      unacceptably high mortality and chronic disability in survivors, underscoring a
      need to validate new approaches for treatment and prognosis. The use of advanced
      imaging, magnetic resonance imaging (MRI) in particular, could help address this
      gap given its versatile capacity to quantitatively evaluate and map changes in
      brain anatomy, physiology and functional activation. Yet there is uncertainty
      about the real value of brain MRI in the clinical setting of aSAH. METHODS: In
      this review, we discuss current and emerging MRI research in aSAH. PubMed was
      searched from inception to June 2017, and additional studies were then chosen on
      the basis of relevance to the topics covered in this review. RESULTS: Available
      studies suggest that brain MRI is a feasible, safe, and valuable testing
      modality. MRI detects brain abnormalities associated with neurologic examination,
      outcomes, and aneurysm treatment and thus has the potential to increase knowledge
      of aSAH pathophysiology as well as to guide management and outcome prediction.
      Newer pulse sequences have the potential to reveal structural and physiological
      changes that could also improve management of aSAH. CONCLUSION: Research is
      needed to confirm the value of MRI-based biomarkers in clinical practice and as
      endpoints in clinical trials, with the goal of improving outcome for patients
      with aSAH.

PMID- 29633157
TI  - Longitudinally extensive spinal cord lesions: not always neuromyelitis optica.

PMID- 29633156
TI  - Uncovering the Rosetta Stone: Report from the First Annual Conference on Key
      Elements in Translating Stroke Therapeutics from Pre-Clinical to Clinical.
AB  - The first annual Stroke Translational Research Advancement Workshop (STRAW),
      entitled "Uncovering the Rosetta Stone: Key Elements in Translating Stroke
      Therapeutics from Pre-Clinical to Clinical" was held at the University of
      Kentucky on October 4-5, 2017. This workshop was organized by the Center for
      Advanced Translational Stroke Science. The workshop consisted of 2 days of
      activities. These included three presentations establishing the areas of research
      in stroke therapeutics, discussing the routes for translation from bench to
      bedside, and identifying successes and failures in the field. On day 2, grant
      funding opportunities and goals for the National Institute for Neurological
      Diseases and Stroke were presented. In addition, the meeting also included break
      out sessions designed to connect researchers in areas of stroke, and to foster
      potential collaborations. Finally, the meeting concluded with an open discussion
      among attendees led by a panel of experts.

PMID- 29633158
TI  - The Explanatory Role of Insomnia in the Relationship between Pain Intensity and
      Posttraumatic Stress Symptom Severity among Trauma-Exposed Latinos in a Federally
      Qualified Health Center.
AB  - Latinos, one of the fastest growing populations in the United States, suffer from
      high rates of posttraumatic stress symptoms (PTS) and its clinical correlates
      (e.g., disability). Although research suggests the experience of pain is closely
      related to PTS among trauma-exposed groups, there has been little exploration of
      the processes that may link pain intensity to greater PTS among trauma-exposed
      Latinos. The current study explored insomnia, a common problem associated with
      both pain intensity and PTS, as a mechanism in the association between pain
      intensity and PTS among trauma-exposed Latinos (N = 208, Mage = 39.39 years, SD =
      11.48) attending a Federally Qualified Health Center. Results indicated that
      insomnia partially explained the relationship between pain intensity and PTS
      total score (B = 0.25, 95% CI [0.12, 0.43]), as well as re-experiencing (B =
      0.09, 95% CI [0.04, 0.17]), avoidance (B = 0.09, 95% CI [0.04, 0.17]), and
      arousal symptoms (B = 0.10, 95% CI [0.04, 0.17]). Future work is needed to
      explore the extent to which insomnia accounts for relations between pain and PTS
      using longitudinal designs to further clarify theoretical health disparity models
      involving these comorbid conditions.

PMID- 29633159
TI  - Impact of Anthracyclines on Diabetes Mellitus Development in B-Cell Lymphoma
      Patients: A Nationwide Population-based Study.
AB  - BACKGROUND AND OBJECTIVES: Although anthracyclines are effective chemotherapeutic
      agents for treating B-cell lymphoma, adverse effects, such as bone marrow
      suppression and cardiotoxicity, limit their clinical application. We assessed
      whether anthracycline treatment also increases the risk for diabetes mellitus in
      patients with B-cell lymphoma. METHODS: Using data obtained from the Taiwanese
      National Health Insurance Research Database from 2004 to 2011, we compared
      overall survival and clinical features for B-cell lymphoma patients administered
      anthracyclines (n = 3147) and those not administered anthracyclines (n = 837).
      The impact of anthracycline treatment on diabetes risk was further investigated
      using a Gray's test and multivariate competing-risk regression models in a dose
      dependent manner. RESULTS: Anthracycline administration was associated with a
      higher incidence of diabetes (HR: 1.75; 95% CI 1.11-2.75; p = 0.0163) after
      adjustments for age, gender, cumulative dose of prednisolone, and co-morbidities.
      Cumulative anthracycline doses of 253-400 mg (HR: 2.35; 95% CI 1.41-3.91; p =
      0.0010), 401-504 mg (HR: 2.26; 95% CI 1.26-4.05; p = 0.0063), and > 504 mg (HR:
      2.29; 95% CI 1.25-4.18; p = 0.0072) increased the incidence density of diabetes
      in a dose-dependent manner (p = 0.0006). The annual alteration of adapted
      diabetes complications severity index score was not significantly different
      between B-cell lymphoma patients with or without anthracycline treatment (p =
      0.4924). CONCLUSION: Anthracycline therapy increases diabetes risk in a dose
      dependent manner in B-cell lymphoma patients. Intensive blood glucose monitoring
      and control should be recommended for B-cell lymphoma patients receiving
      anthracycline treatment.

PMID- 29633161
TI  - Have bailouts shifted the burden of paying for healthcare from the state onto
      individuals?
AB  - BACKGROUND/AIMS: The financial crisis that enveloped Europe in 2009 created
      financial pressure for governments and required a number of countries to obtain a
      financial bailout from the IMF. The purpose of this paper is to examine the
      effect of the financial crisis on public health expenditure in bailout countries
      and if bailouts shift the burden of paying for healthcare from the state onto
      individuals. METHODS: Quantitative health expenditure data were collected from
      the WHO and OECD for the period 2004-2015 and evaluated using a comparison of
      means Welch's t test. RESULTS: The majority of bailout countries recorded a
      decrease in public health expenditure as a percentage of total government
      expenditure, with Ireland recording the largest decrease with government health
      expenditure as a percentage of total government expenditure, falling by 22% (P <
      .01). In addition, the results also suggest that the burden of paying for
      healthcare shifted from the state onto individuals in three countries, namely
      Hungary, Ireland and Portugal, where public health expenditure declined and
      private expenditure increased significantly. CONCLUSIONS: The ramifications of
      shifting the burden of paying for healthcare from the state onto individuals at
      this point remain unclear with further research required to identify the long
      term consequences for healthcare.

PMID- 29633160
TI  - A Cost-Effectiveness Analysis of the 10-Valent Pneumococcal Non-Typeable
      Haemophilus influenzae Protein D Conjugate Vaccine (PHiD-CV) Compared to the 13
      Valent Pneumococcal Conjugate Vaccine (PCV13) for Universal Mass Vaccination
      Implementation in New Zealand.
AB  - OBJECTIVES: Invasive pneumococcal disease (IPD), pneumonia and acute otitis media
      (AOM) still represent a significant medical burden in children < 5 years of age
      in New Zealand (NZ), with marked disparities across socio-economic and ethnic
      groups. This cost-effectiveness evaluation aims to compare the potential impact
      of two childhood universal immunisation strategies: vaccination with a 3 + 1
      schedule of the 10-valent pneumococcal non-typeable Haemophilus influenzae
      protein D conjugate vaccine (PHiD-CV, Synflorix, GSK) and the 13-valent
      pneumococcal conjugate vaccine (PCV13, Prevenar 13, Pfizer). METHODS: A static
      Markov-process cohort model was used to simulate the epidemiological and economic
      burden of pneumococcal diseases on a single-birth cohort over its lifetime. Costs
      and outcomes were discounted annually at 3.5%. Epidemiological and cost inputs
      were extracted from the most recently available NZ data, or derived from the most
      relevant reference countries' sources. The most updated evidence on the
      efficacies of the corresponding vaccines were used, particularly the significant
      effectiveness for PHiD-CV against IPD caused by serotype 19A. RESULTS: The model
      estimated that both vaccines have a broadly comparable impact on IPD-related
      diseases and pneumonia. Due to the additional benefits possible through broader
      impact on AOM, PHiD-CV is estimated to potentially provide additional discounted
      cost offsets of approximately NZD 0.8 million over the lifetime of the birth
      cohort. CONCLUSIONS: To ensure health equity in children, given the substantial
      burden of pneumonia and AOM, decision-makers should also take into account the
      impact of PCVs on these diseases for decisions relating to routine infant
      immunization. GSK STUDY IDENTIFIER: HO-15-16775.

PMID- 29633162
TI  - Caffeine, CYP1A2 genotype, and sports performance: is timing important?

PMID- 29633163
TI  - Festschrift for Patrick Ronan (PR) O'Connell (also known as ROCON): reconciling
      surgery and science.
AB  - Ronan O Connell's clinical activities were fundamentally based on accurate data.
      His scientific outputs were based on similarly high quality data. Anybody who
      trained with him and in particular those who trained with him on more than
      occasion base their clinical and scientific activities on a similar approach. His
      many clinical, scientific and political achievements and accolades will be
      detailed in the articles in this Festschrift. There is an advancement that is
      important to me personally and that I would like to attribute to his influence.
      Exceptional and highly reproducible technique underpinned his surgery and
      explained the outcomes his patients experienced. Recent clarification of the
      anatomical basis of these techniques (the mesenteric basis) provides a unifying
      platform across which to reconcile human abdominal anatomy and surgery.

PMID- 29633164
TI  - Xueshuantong Injection (Lyophilized) Attenuates Cerebral Ischemia/Reperfusion
      Injury by the Activation of Nrf2-VEGF Pathway.
AB  - Xueshuantong injection (Lyophilized, XST), extracted from the traditional Chinese
      medicinal herb Panax notoginseng, has neuroprotective effect on cerebral
      ischemia. Revascularization of ischemic tissue is good for the therapy of
      cerebrovascular disease. In this study, angiogenic potentiality and possible
      mechanism of XST for cerebral ischemia were explored. Rats were subjected to
      transient middle cerebral artery occlusion (MCAO), and then intraperitoneally
      administered with XST daily for 3 or 7 consecutive days. The neurological
      function deficits, and endogenous antioxidant capacity were evaluated. Post
      stroke angiogenesis and vascularization were assessed by ELISA and
      immunohistochemical staining. Transcription levels of Nrf2, HO-1, NQO1 in brain
      tissues were analyzed by real-time RT-PCR. The results showed that XST could
      remarkably ameliorate neuronal functional deficit, promote angiogenesis and
      vascularization after MCAO. The mechanism of angiogenesis might be related to
      endogenous antioxidant capacity and Nrf2 pathway. In conclusion, administered XST
      for 7 days after stroke could significantly improve functional recovery and
      promote angiogenesis, that might be related to Nrf2 signaling pathway. These
      findings could provide scientific evidence for the use of XST in cerebral
      ischemic diseases and provide theoretical support for further studies.

PMID- 29633165
TI  - Health state utility values of high prevalence mental disorders in Australia:
      results from the National Survey of Mental Health and Wellbeing.
AB  - PURPOSE: High prevalence mental disorders including depression, anxiety and
      substance use disorders are associated with high economic and disease burden.
      However, there is little information regarding the health state utility values of
      such disorders according to their clinical severity using comparable instruments
      across all disorders. This study reports utility values for high prevalence
      mental disorders using data from the 2007 Australian National Survey of Mental
      Health and Wellbeing (NSMHWB). METHODS: Utility values were derived from the AQoL
      4D and analysed by disorder classification (affective only (AD), anxiety-related
      only (ANX), substance use only (SUB) plus four comorbidity groups), severity
      level (mild, moderate, severe), symptom recency (reported in the past 30 days),
      and comorbidity (combination of disorders). The adjusted Wald test was applied to
      detect statistically significant differences of weighted means and the magnitude
      of difference between groups was presented as a modified Cohen's d. RESULTS: In
      total, 1526 individuals met criteria for a 12-month mental disorder. The mean
      utility value was 0.67 (SD = 0.27), with lower utility values associated with
      higher severity levels and some comorbidities. Utility values for AD, ANX and SUB
      were 0.64 (SD = 0.25), 0.71 (SD = 0.25) and 0.81 (SD = 0.19), respectively. No
      differences in utility values were observed between disorders within disorder
      groups. Utility values were significantly lower among people with recent symptoms
      (within past 30 days) than those without; when examined by diagnostic group, this
      pattern held for people with SUB, but not for people with ANX or AD. CONCLUSIONS:
      Health state utility values of people with high prevalence mental disorders
      differ significantly by severity level, number of mental health comorbidities and
      the recency of symptoms, which provide new insights on the burden associated with
      high prevalence mental disorders in Australia. The derived utility values can be
      used to populate future economic models.

PMID- 29633166
TI  - A Phase 3, Double-Blind, Randomized, Placebo-Controlled Study of Vilazodone in
      Adolescents with Major Depressive Disorder.
AB  - BACKGROUND: Major depressive disorder (MDD) is a serious illness in children and
      adolescents. Vilazodone is a selective serotonin reuptake inhibitor approved for
      MDD in adults. This study evaluated the efficacy, safety, and tolerability of
      vilazodone in adolescent patients, ages 12-17 years, with MDD (NCT01878292).
      METHODS: This double-blind, randomized, placebo-controlled, parallel-group, fixed
      dose study was conducted at 56 study centers in the United States and was 10
      weeks in duration (a 1-week screening period, an 8-week double-blind treatment
      period, and a 1-week double-blind down-taper period). Outpatients with an MDD
      diagnosis based on Diagnostic and Statistical Manual of Mental Disorders, Fourth
      Edition, Text Revision criteria were included in the study. Clinical inclusion
      criteria required a Children's Depression Rating Scale-Revised (CDRS-R) total
      score of >= 40 and Clinical Global Impressions-Severity (CGI-S) score of >= 4.
      Patients were randomized 1:1:1 to 8 weeks of double-blind treatment with placebo
      (n = 174), vilazodone 15 mg/day (n = 175), or vilazodone 30 mg/day (n = 180). The
      primary and secondary efficacy parameters were change from baseline to week 8 in
      CDRS-R total score and CGI-S score, respectively. Safety parameters included
      adverse events (AEs); clinical laboratory, vital sign, and electrocardiogram
      parameters; and the Columbia-Suicide Severity Rating Scale. RESULTS:
      Approximately 86% of patients completed double-blind treatment. There was no
      statistically significant difference between vilazodone 15 mg/day or 30 mg/day
      and placebo in change from baseline in CDRS-R score. Change in CGI-S score was
      not significant after adjustment for multiple comparisons. The most common
      treatment-emergent AEs were nausea, upper abdominal pain, vomiting, diarrhea,
      nasopharyngitis, headache, and dizziness. Reports of suicidal ideation (placebo,
      33.3%; vilazodone 15 mg/day, 36.0%; vilazodone 30 mg/day, 31.1%) and suicidal
      behavior (placebo, 1.8%; vilazodone 15 mg/day, 1.1%; vilazodone 30 mg/day, 1.1%)
      were similar between treatment groups. There were no deaths in the study.
      CONCLUSIONS: The efficacy of vilazodone for the treatment of MDD in adolescent
      patients could not be confirmed in this study. Vilazodone was generally safe and
      well tolerated, with treatment-emergent AEs similar to those in adult patients.
      CLINICAL TRIAL REGISTRATION: NCT01878292.

PMID- 29633169
TI  - Elevated post-void residual volume in a geriatric post-hip fracture assessment in
      women-associated factors and risk of mortality.
AB  - BACKGROUND AND AIM: Multiple factors contribute to elevated post-void residual
      urine volumes (PVR), but they may indicate detrusor underactivity (DU),
      especially in older women. The aim here was to examine factors associated with
      and prognostic significance of elevated PVR in a geriatric post-hip fracture
      assessment in a female population. METHODS: Consecutive female hip fracture
      patients (n = 409) aged 65 years and older were included. PVR was measured by
      bladder scanner. PVR of 160 ml or more was deemed elevated. Age-adjusted
      univariate logistic regression analyses were conducted to examine the association
      of the domains of the comprehensive geriatric assessment (CGA) with elevated PVR.
      Cox proportional hazards model was used to determine the age-adjusted association
      of an elevated PVR with 1-year mortality. RESULTS: Of the patients, 64 (15.6%)
      had elevated PVR. Having urinary or fecal incontinence, difficulties in physical
      activities of daily living, malnutrition, poor performance on Timed Up and Go and
      Elderly Mobility Scale were significantly associated with elevated PVR.
      Difficulties in instrumental activities of daily living, renal dysfunction,
      constipation, polypharmacy, nocturia, cognitive impairment and depressive mood
      were not associated with elevated PVR. Elevated PVR significantly increased the
      risk of mortality 1 year post hip fracture. CONCLUSIONS: Elevated PVR is
      relatively common in older female hip fracture patients and associated with
      physical functioning, malnutrition and risk of mortality. Even though a causal
      relationship cannot be confirmed, the findings may suggest a relationship between
      DU and physical frailty. PVR deserves to be included in the CGA of frail older
      patients including women.

PMID- 29633170
TI  - Related factors of cognitive impairment in community-dwelling older adults in
      Beijing Longitudinal Study of Aging.
AB  - OBJECTIVES: To investigate the prevalence and related factors of cognitive
      impairment in community-dwelling older residents in Beijing, China. METHODS: This
      is a cross-sectional study. A total of 2017 older individuals aged >= 60 years
      from Beijing Longitudinal Study of Aging were included in this study. Information
      on demographic characteristics, life style, chronic disease and geriatric
      syndromes was collected. Cognitive function was assessed by Mini-Mental State
      Examination. RESULTS: The prevalence of cognitive impairment was 13.6% in
      community-dwelling older residents in Beijing. The prevalence of cognitive
      impairment was higher in women than it was in men and in rural areas than it was
      in urban areas, and increased with age. Logistic regression showed that older age
      [odds ratio (OR) = 1.496-3.033, P < 0.001], illiteracy (OR = 1.200-2.434, P =
      0.003), low income (OR = 1.268-3.906, P = 0.005), less social participation (OR =
      1.011-2.147, P = 0.044), stroke (OR = 1.410-3.305, P < 0.001), hearing loss (OR =
      1.231-2.295, P = 0.001), depression (OR = 1.115-2.385, P = 0.012) and disability
      (OR = 2.315-4.681, P < 0.001) were independent risk factors for cognitive
      impairment. CONCLUSIONS: The prevalence of cognitive impairment among the older
      adults in Beijing was high. More attention should be paid to the identification
      of and intervention for factors influencing cognitive impairment, and health
      education should be carried out to improve the quality of life of the older
      adults.

PMID- 29633168
TI  - Expression of VGRNb-PE immunotoxin in transplastomic lettuce (Lactuca sativa L.).
AB  - KEY MESSAGE: This research has shown, for the first time, that plant chloroplasts
      are a suitable compartment for synthesizing recombinant immunotoxins and the
      transgenic immunotoxin efficiently causes the inhibition of VEGFR2
      overexpression, cell growth and proliferation. Angiogenesis refers to the
      formation of new blood vessels, which resulted in the growth, invasion and
      metastasis of cancer. The vascular endothelial growth factor receptor 2 (VEGFR2)
      plays a major role in angiogenesis and blocking of its signaling inhibits
      neovascularization and tumor metastasis. Immunotoxins are promising therapeutics
      for targeted cancer therapy. They consist of an antibody linked to a protein
      toxin and are designed to specifically kill the tumor cells. In our previous
      study, VGRNb-PE immunotoxin protein containing anti-VEGFR2 nanobody fused to the
      truncated form of Pseudomonas exotoxin A has been established. Here, we expressed
      this immunotoxin in lettuce chloroplasts. Chloroplast genetic engineering offers
      several advantages, including high levels of transgene expression, multigene
      engineering in a single transformation event and maternal inheritance of the
      transgenes. Site specific integration of transgene into chloroplast genomes, and
      homoplasmy were confirmed. Immunotoxin levels reached up to 1.1% of total soluble
      protein or 33.7 ug per 100 mg of leaf tissue (fresh weight). We demonstrated that
      transgenic immunotoxin efficiently causes the inhibition of VEGFR2
      overexpression, cell growth and proliferation. These results indicate that plant
      chloroplasts are a suitable compartment for synthesizing recombinant
      immunotoxins.

PMID- 29633167
TI  - Proteomic and physiological analyses reveal the role of exogenous spermidine on
      cucumber roots in response to Ca(NO3)2 stress.
AB  - KEY MESSAGE: The mechanism of exogenous Spd-induced Ca(NO3)2 stress tolerance in
      cucumber was studied by proteomics and physiological analyses. Protein-protein
      interaction network revealed 13 key proteins involved in Spd-induced Ca(NO3)2
      stress resistance. Ca(NO3)2 stress is one of the major reasons for secondary
      salinization that limits cucumber plant development in greenhouse. The conferred
      protective role of exogenous Spd on cucumber in response to Ca(NO3)2 stress cues
      involves changes at the cellular and physiological levels. To investigate the
      molecular foundation of exogenous Spd in Ca(NO3)2 stress tolerance, a proteomic
      approach was performed in our work. After a 9 days period of Ca(NO3)2 stress
      and/or exogenous Spd, 71 differential protein spots were confidently identified.
      The resulting proteins were enriched in seven different categories of biological
      processes, including protein metabolism, carbohydrate and energy metabolism, ROS
      homeostasis and stress defense, cell wall related, transcription, others and
      unknown. Protein metabolism (31.2%), carbohydrate and energy metabolism (15.6%),
      ROS homeostasis and stress defense (32.5%) were the three largest functional
      categories in cucumber root and most of them were significantly increased by
      exogenous Spd. The Spd-responsive protein interaction network revealed 13 key
      proteins, whose accumulation changes could be critical for Spd-induced
      resistance; all 13 proteins were upregulated by Spd at transcriptional and
      protein levels in response to Ca(NO3)2 stress. Furthermore, accumulation of
      antioxidant enzymes, non-enzymatic antioxidant and polyamines, along with
      reduction of H2O2 and MDA, were detected after exogenous Spd application during
      Ca(NO3)2 stress. The results of these proteomic and physiological analyses in
      cucumber root may facilitate a better understanding of the underlying mechanism
      of Ca(NO3)2 stress tolerance mediated by exogenous Spd.

PMID- 29633171
TI  - Imaging the operated colon using water-enema multidetector CT, with emphasis on
      surgical anastomoses.
AB  - : Water-enema multidetector CT (WE-MDCT) provides a detailed multiplanar
      visualisation of mural, intra- and extraluminal abnormalities of the large bowel,
      relying on preliminary bowel cleansing, retrograde luminal distension,
      pharmacological hypotonisation and intravenous contrast enhancement. In patients
      with a history of colorectal surgery for either carcinoma or Crohn's disease
      (CD), WE-MDCT may also be performed via a colostomy, which allows depicting the
      anatomy and position of the residual large bowel and evaluates the calibre,
      length, mural and extraluminal features of luminal strictures. Therefore, WE-MDCT
      may prove useful as a complementary technique after incomplete or inconclusive
      colonoscopy to assess features and suspected abnormalities of the surgical
      anastomosis, particularly when endoscopic or surgical interventions are being
      planned. This pictorial essay presents the WE-MDCT technique and pitfalls, the
      expected appearances after different colic surgeries and the imaging features of
      benign anastomotic disorders (fibrotic stricture, kinking, inflammatory ulcer)
      and of locally recurrent tumours and CD. TEACHING POINTS: * Water-enema
      multidetector CT (WE-MDCT) effectively visualises the operated colon *
      Complementary to endoscopy, WE-MDCT may helpfully depict abnormalities of
      surgical anastomoses * WE-MDCT allows assessment of strictures' features and
      abnormalities of the upstream bowel * Technical pitfalls, normal postsurgical
      findings and benign anastomotic disorders are presented * WE-MDCT allows
      detecting relapsing Crohn's disease, recurrent and metachronous tumours.

PMID- 29633173
TI  - Study of continuous blood pressure estimation based on pulse transit time, heart
      rate and photoplethysmography-derived hemodynamic covariates.
AB  - It is widely recognized that pulse transit time (PTT) can track blood pressure
      (BP) over short periods of time, and hemodynamic covariates such as heart rate,
      stiffness index may also contribute to BP monitoring. In this paper, we derived a
      proportional relationship between BP and PPT-2 and proposed an improved method
      adopting hemodynamic covariates in addition to PTT for continuous BP estimation.
      We divided 28 subjects from the Multi-parameter Intelligent Monitoring for
      Intensive Care database into two groups (with/without cardiovascular diseases)
      and utilized a machine learning strategy based on regularized linear regression
      (RLR) to construct BP models with different covariates for corresponding groups.
      RLR was performed for individuals as the initial calibration, while recursive
      least square algorithm was employed for the re-calibration. The results showed
      that errors of BP estimation by our method stayed within the Association of
      Advancement of Medical Instrumentation limits (- 0.98 +/- 6.00 mmHg @ SBP, 0.02
      +/- 4.98 mmHg @ DBP) when the calibration interval extended to 1200-beat cardiac
      cycles. In comparison with other two representative studies, Chen's method kept
      accurate (0.32 +/- 6.74 mmHg @ SBP, 0.94 +/- 5.37 mmHg @ DBP) using a 400-beat
      calibration interval, while Poon's failed (- 1.97 +/- 10.59 mmHg @ SBP, 0.70 +/-
      4.10 mmHg @ DBP) when using a 200-beat calibration interval. With additional
      hemodynamic covariates utilized, our method improved the accuracy of PTT-based BP
      estimation, decreased the calibration frequency and had the potential for better
      continuous BP estimation.

PMID- 29633174
TI  - Glossokinetic potential based tongue-machine interface for 1-D extraction.
AB  - The tongue is an aesthetically useful organ located in the oral cavity. It can
      move in complex ways with very little fatigue. Many studies on assistive
      technologies operated by tongue are called tongue-human computer interface or
      tongue-machine interface (TMI) for paralyzed individuals. However, many of them
      are obtrusive systems consisting of hardware such as sensors and magnetic tracer
      placed in the mouth and on the tongue. Hence these approaches could be annoying,
      aesthetically unappealing and unhygienic. In this study, we aimed to develop a
      natural and reliable tongue-machine interface using solely glossokinetic
      potentials via investigation of the success of machine learning algorithms for 1
      D tongue-based control or communication on assistive technologies. Glossokinetic
      potential responses are generated by touching the buccal walls with the tip of
      the tongue. In this study, eight male and two female naive healthy subjects, aged
      22-34 years, participated. Linear discriminant analysis, support vector machine,
      and the k-nearest neighbor were used as machine learning algorithms. Then the
      greatest success rate was achieved an accuracy of 99% for the best participant in
      support vector machine. This study may serve disabled people to control assistive
      devices in natural, unobtrusive, speedy and reliable manner. Moreover, it is
      expected that GKP-based TMI could be alternative control and communication
      channel for traditional electroencephalography (EEG)-based brain-computer
      interfaces which have significant inadequacies arisen from the EEG signals.

PMID- 29633172
TI  - Freeze-dried matrices for ocular administration of bevacizumab: a comparison
      between subconjunctival and intravitreal administration in rabbits.
AB  - This work was aimed to tune solid matrices for bevacizumab (BVZ) subconjunctival
      or intravitreal administration in order to prolong drug release, to reduce the
      number of applications and consequently the side effects. Matrices, with sizes
      suitable for intravitreal or subconjunctival administration, based on
      hydroxypropylmethyl cellulose (HPMC), polyvinylpyrrolidone (PVP), polyvinyl
      alcohol (PVA) and polyacrylic acid (PAA) were obtained by freeze-drying of
      polymeric dispersions either in phosphate buffer solution or water and were
      sterilized by gamma rays. The matrices were characterized from the technological
      point of view and evaluated for in vitro release of dextran and BVZ. In vivo
      evaluation of BVZ release in ocular humours was finally carried out on rabbits.
      The obtained matrices showed solvent sorption time ranging from a few seconds for
      PAA to 46 min for HPMC, with shorter times when prepared in buffer solution. The
      hydration times were up to 5.5-fold higher after sterilization. HPMC and PVA
      matrices showed a slowdown of the release rate of both dextran and BVZ, but HPMC
      was selected for following in vivo studies also in consideration of its higher
      viscosity after rehydration of the matrix. HPMC matrix was well tolerated by the
      rabbit eye when intravitreally and subconjunctivally administered. The different
      treatment produced the same effect in terms of drug concentration in aqueous and
      vitreous humour up to 12 weeks after administration. The results of this study
      support the possible use of lyophilized matrices as a BVZ delivery system to the
      posterior segment of the eye.

PMID- 29633175
TI  - Race/Ethnicity Differences in Trends of Marijuana, Cigarette, and Alcohol Use
      Among 8th, 10th, and 12th Graders in Washington State, 2004-2016.
AB  - Accurate estimates of substance use in the teenage years by race/ethnicity may
      help identify when to intervene to prevent long-term substance use disparities.
      We examined trends in past 30-day use of marijuana, cigarette, and alcohol among
      8th, 10th, and 12th graders in Washington State, which passed a recreational
      marijuana law in 2012 and initiated retail marijuana sales in 2014. Data are from
      the 2004-2016 Washington Healthy Youth Surveys (n = 161,992). We used time series
      regression models to assess linear and quadratic trends in substance use for the
      full sample and stratified on race/ethnicity and grade level and examined
      relative differences in prevalence of use by race/ethnicity. In Washington,
      across all racial/ethnic groups, marijuana use peaked in 2012. Although there was
      not a significant overall change in marijuana use for the full sample across the
      study period, there was a statistically significant increase in use among 12th
      graders and a statistically significant decrease among 8th graders. Relative to
      Whites, Asians had a lower prevalence of marijuana use, whereas all other
      race/ethnicity groups had a higher prevalence of use. Prevalence of marijuana use
      is particularly high among American Indian/Alaska Native and Black youth and has
      increased most rapidly among 12th grade Hispanic/Latinx youth. There were large
      and statistically significant decreases in alcohol and cigarette use across the
      study period for the full sample, as well as for each race/ethnicity group. These
      findings highlight the need for continued monitoring of trends in use among these
      groups and potentially warrant consideration of selective interventions that
      specifically focus on students of color and that include developmentally
      appropriate strategies relevant to each grade.

PMID- 29633176
TI  - Promoting Adolescent Girls' Well-Being in Pakistan: a Mixed-Methods Study of
      Change Over Time, Feasibility, and Acceptability, of the COMPASS Program.
AB  - Promoting resilience among displaced adolescent girls in northern Pakistan may
      buffer against developmental risks such as violence exposure and associated
      longer-term consequences for physical and mental well-being. However, girls'
      access to such programming may be limited by social norms restricting movement. A
      mixed-method evaluation examined change over time, feasibility, and acceptability
      of the COMPASS program in three districts of Khyber-Pakhtunkhwa province through
      a single-group within-participant pretest-posttest of adolescent girls aged 12-19
      enrolled in the intervention (n = 78), and qualitative in-depth interviews with
      girls following posttest completion (n = 15). Primary outcomes included
      improvements in movement, safety, and comfort discussing life skills topics with
      caregivers, operationalized quantitatively as number of places visited in the
      previous month, number of spaces that girls felt safe visiting, and comfort
      discussing puberty, education, working outside the home, and marriage,
      respectively. Secondary outcomes included psychosocial well-being, gendered rites
      of passage, social support networks, perceptions of support for survivors of
      violence, and knowledge of services. Quantitative pretest-posttest findings
      included significant improvements in movement, psychosocial well-being, and some
      improvements in social support, knowledge of services, and gendered rites of
      passage; findings on safety and comfort discussing life skills topics were not
      significant. Qualitative findings illuminated themes related to definitions of
      safety and freedom of movement, perceptions and acceptability of program content,
      perceptions of social support, and perceptions of blame and support and knowledge
      of services in response to violence. Taken together, findings illustrate positive
      impacts of life skills programming, and the need for societal changes on gender
      norms to improve girls' safety in public spaces and access to resources.

PMID- 29633177
TI  - In Vitro Bactericidal and Virucidal Efficacy of Povidone-Iodine Gargle/Mouthwash
      Against Respiratory and Oral Tract Pathogens.
AB  - INTRODUCTION: Recent virus epidemics and rising antibiotic resistance highlight
      the importance of hygiene measures to prevent and control outbreaks. We
      investigated the in vitro bactericidal and virucidal efficacy of povidone-iodine
      (PVP-I) 7% gargle/mouthwash at defined dilution against oral and respiratory
      tract pathogens. METHODS: PVP-I was tested against Klebsiella pneumoniae and
      Streptococcus pneumoniae according to bactericidal quantitative suspension test
      EN13727 and against severe acute respiratory syndrome and Middle East respiratory
      syndrome coronaviruses (SARS-CoV and MERS-CoV), rotavirus strain Wa and influenza
      virus A subtype H1N1 according to virucidal quantitative suspension test EN14476.
      PVP-I 7% gargle/mouthwash was diluted 1:30 with water to a concentration of 0.23%
      (the recommended concentration for "real-life" use in Japan) and tested at room
      temperature under clean conditions [0.3 g/l bovine serum albumin (BSA), viruses
      only] and dirty conditions (3.0 g/l BSA + 3.0 ml/l erythrocytes) as an
      interfering substance for defined contact times (minimum 15 s). Rotavirus was
      tested without protein load. A >= 5 log10 (99.999%) decrease of bacteria and >= 4
      log10 (99.99%) reduction in viral titre represented effective bactericidal and
      virucidal activity, respectively, per European standards. RESULTS: PVP-I
      gargle/mouthwash diluted 1:30 (equivalent to a concentration of 0.23% PVP-I)
      showed effective bactericidal activity against Klebsiella pneumoniae and
      Streptococcus pneumoniae and rapidly inactivated SARS-CoV, MERS-CoV, influenza
      virus A (H1N1) and rotavirus after 15 s of exposure. CONCLUSION: PVP-I 7%
      gargle/mouthwash showed rapid bactericidal activity and virucidal efficacy in
      vitro at a concentration of 0.23% PVP-I and may provide a protective
      oropharyngeal hygiene measure for individuals at high risk of exposure to oral
      and respiratory pathogens. FUNDING: Mundipharma Research GmbH & Co. KG (MRG).

PMID- 29633178
TI  - Pharmacology of MDMA- and Amphetamine-Like New Psychoactive Substances.
AB  - New psychoactive substances (NPS) with amphetamine-, aminoindan-, and benzofuran
      basic chemical structures have recently emerged for recreational drug use.
      Detailed information about their psychotropic effects and health risks is often
      limited. At the same time, it emerged that the pharmacological profiles of these
      NPS resemble those of amphetamine or 3,4-methylenedioxymethamphetamine (MDMA).
      Amphetamine-like NPS induce psychostimulation and euphoria mediated predominantly
      by norepinephrine (NE) and dopamine (DA) transporter (NET and DAT) inhibition and
      transporter-mediated release of NE and DA, thus showing a more catecholamine
      selective profile. MDMA-like NPS frequently induce well-being, empathy, and
      prosocial effects and have only moderate psychostimulant properties. These MDMA
      like substances primarily act by inhibiting the serotonin (5-HT) transporter
      (SERT) and NET, also inducing 5-HT and NE release. Monoamine receptor
      interactions vary considerably among amphetamine- and MDMA-like NPS. Clinically,
      amphetamine- and MDMA-like NPS can induce sympathomimetic toxicity. The aim of
      this chapter is to review the state of knowledge regarding these substances with
      a focus on the description of the in vitro pharmacology of selected amphetamine-
      and MDMA-like NPS. In addition, it is aimed to provide links between
      pharmacological profiles and in vivo effects and toxicity, which leads to the
      conclusion that abuse liability for amphetamine-like NPS may be higher than for
      MDMA-like NPS, but that the risk for developing the life-threatening serotonin
      syndrome may be increased for MDMA-like NPS.

PMID- 29633179
TI  - Brown-Like Adipocyte Progenitors Derived from Human iPS Cells: A New Tool for
      Anti-obesity Drug Discovery and Cell-Based Therapy?
AB  - Alternative strategies are urgently required to fight obesity and associated
      metabolic disorders including diabetes and cardiovascular diseases. Brown and
      brown-like adipocytes (BAs) store fat, but in contrast to white adipocytes,
      activated BAs are equipped to dissipate energy stored. Therefore, BAs represent
      promising cell targets to counteract obesity. However, the scarcity of BAs in
      adults is a major limitation for a BA-based therapy of obesity, and the notion to
      increase the BA mass by transplanting BA progenitors (BAPs) in obese patients
      recently emerged. The next challenge is to identify an abundant and reliable
      source of BAPs. In this chapter, we describe the capacity of human-induced
      pluripotent stem cells (hiPSCs) to generate BAPs able to differentiate at a high
      efficiency with no gene transfer. This cell model represents an unlimited source
      of human BAPs that in a near future may be a suitable tool for both therapeutic
      transplantation and for the discovery of novel efficient and safe anti-obesity
      drugs. The generation of a relevant cell model, such as hiPSC-BAs in 3D
      adipospheres enriched with macrophages and endothelial cells to better mimic the
      microenvironment within the adipose tissue, will be the next critical step.

PMID- 29633180
TI  - Role of cAMP and cGMP Signaling in Brown Fat.
AB  - Cold-induced activation of brown adipose tissue (BAT) is mediated by
      norepinephrine and adenosine that are released during sympathetic nerve
      activation. Both signaling molecules induce an increase in intracellular levels
      of 3',5'-cyclic adenosine monophosphate (cAMP) in murine and human BAT. In brown
      adipocytes, cAMP plays a central role, because it activates lipolysis, glucose
      uptake, and thermogenesis. Another well-studied intracellular second messenger is
      3',5'-cyclic guanosine monophosphate (cGMP), which closely resembles cAMP.
      Several studies have shown that intact cGMP signaling is essential for normal
      adipogenic differentiation and BAT-mediated thermogenesis in mice. This chapter
      highlights recent observations, demonstrating the physiological significance of
      cyclic nucleotide signaling in BAT as well as their potential to induce browning
      of white adipose tissue (WAT) in mice and humans.

PMID- 29633181
TI  - Evidence and Function Relevance of Native DOR-MOR Heteromers.
AB  - Opioid receptors are the sites of action for morphine and most other clinically
      used opioid drugs. Abundant evidence now demonstrates that different opioid
      receptor types can physically associate to form heteromers. Owing to their
      constituent monomers' involvement in analgesia, mu/delta opioid receptor (M/DOR)
      heteromers have been a particular focus of attention. Understandings of the
      physiological relevance and indisputable proof of M/DOR formation in vivo are
      still evolving. This aspect of the field has been slow to progress in large part
      by the limitations of most available experimental models; recently however,
      promising progress is being made. As a result, the long-repeated promise of
      opioid receptor heteromers as selective therapeutic targets is now being
      realized.

PMID- 29633182
TI  - BAT Exosomes: Metabolic Crosstalk with Other Organs and Biomarkers for BAT
      Activity.
AB  - In the last decade, exosomes have gained interest as a new type of intercellular
      communication between cells and tissues. Exosomes are circulating, cell-derived
      lipid vesicles smaller than 200 nm that contain proteins and nucleic acids,
      including microRNAs (miRNAs), and are able to modify cellular targets. Exosomal
      miRNAs function as signalling molecules that regulate the transcription of their
      target genes and can cause phenotypic transformation of recipient cells. Recent
      studies have shown that brown fat secretes exosomes as a form of communication
      with other metabolic organs such as the liver. Moreover, it has been shown that
      levels of miRNAs in BAT-derived exosomes change after BAT activation in vitro and
      in vivo. Thus, BAT-derived exosomes can be used as potential biomarkers of BAT
      activity. Here, we review the present knowledge about BAT-derived exosomes and
      their role in metabolism.

PMID- 29633183
TI  - General recommendations paper on the management of older patients with cancer:
      the SEOM geriatric oncology task force's position statement.
AB  - Population aging is associated with greater numbers of older people with cancer.
      Thanks to treatment advances, not only are more seniors diagnosed with cancer,
      but there are also more and more older cancer survivors. This upward trend will
      continue. Given the heterogeneity of aging, managing older patients with cancer
      poses a significant challenge for Medical Oncology. In Spain, a Geriatric
      Oncology Task Force has been set up within the framework of the Spanish Society
      for Medical Oncology (SEOM). With the aim of generating evidence and raising
      awareness, as well as helping medical oncologists in their training with respect
      to seniors with cancer, we have put together a series of basic management
      recommendations for this population. Many of the patients who are assessed in
      routine clinical practice in Oncology are older. CGA is the basic tool by means
      of which to evaluate older people with cancer and to understand their needs.
      Training and the correct use of recommendations regarding treatment for
      comorbidities and geriatric syndromes, support care, and drug-drug interactions
      and toxicities, including those of antineoplastic agents, as detailed in this
      article, will ensure that this population is properly managed.

PMID- 29633184
TI  - Evaluation of waiting times for breast cancer diagnosis and surgical treatment.
AB  - PURPOSE: To analyse any delays in breast cancer diagnosis and surgical treatment,
      influence of clinical and biological factors and influence of delays on survival.
      METHODS/PATIENTS: A descriptive, observational, and retrospective study was
      conducted between 2006 and 2016 on stages I-III breast cancer patients. This is a
      retrospective review of health records to collect data on delays, patients'
      clinical data, biological features of the tumour and information on treatment.
      Mortality data from the National Death Index. RESULTS: In 493 evaluable patients,
      the median of days from the first symptom to mammography, biopsy, and surgery was
      41, 57, and 92, respectively. The median of days from screening mammography to
      biopsy and surgery was 10 and 51, respectively. From biopsy to surgery, the
      median was 34 days in every case. Over the last 5 years, an increase in biopsy
      surgery delay has been observed (p = 0.0001). Tumour stages I and II vs. stage
      III (RR 1.74. 95% CI 1.08-2.80, p = 0.027), diagnosis in screening (RR 0.66. 95%
      CI 0.45-0.96, p = 0.030), and use of magnetic resonance imaging (RR 2.08. 95 CI
      1.21-3.56, p = 0.008) condition a greater biopsy-surgery delay. No influence of
      delays on survival has been identified. CONCLUSIONS: Delays in diagnosis and
      surgery in the case of women diagnosed on the basis of symptoms may be improved.
      There is a temporary tendency to a greater delay in surgery. Some clinical and
      biological factors must be taken into account to optimise delays. Survival
      results are not adversely affected by delays.

PMID- 29633185
TI  - Re-expression of microRNA-4319 inhibits growth of prostate cancer via Her-2
      suppression.
AB  - PURPOSE: Her-2 is an epidermal growth factor receptor expressed in some prostate
      cancers (PC) associated with outgrowth of the tumor. Dysregulation of some
      microRNAs is involved in the regulation of PC pathogenesis, whereas the role of
      miR-4319 in PC is unknown and addressed in the current study. METHODS: The levels
      of miR-4319 in PC tissues were determined by RT-qPCR and their association with
      patient survival was studied by Kaplan-Meier analysis. Targeted genes for miR
      4319 were predicted by a bioinformatics algorithm and confirmed by a dual
      luciferase reporter assay. Growth of cells of overexpression or inhibition of miR
      4319 or Her-2 was analyzed by an MTT assay. Cell survival in response to a
      chemotherapeutic drug, estramustine (EM), was analyzed by CCK-8 assay. Cell
      apoptosis was evaluated by TUNEL assay and Western blotting for apoptosis
      associated proteins. RESULTS: MiR-4319 levels were decreased in PC specimens,
      compared to corresponding normal prostate tissue. Lower levels of miR-4319 were
      correlated with poorer overall patients' survival. In vitro, the cell survival
      mediated with Her-2 against chemotherapy was inhibited by overexpression of miR
      4319 and was enhanced by depletion of miR-4319. Depletion of miR-4319 in primary
      prostate epithelial cells increased Her-2-dependent cell growth, while re
      expression of miR-4319 in PC cells inhibited Her-2-dependent cell growth and Her
      2-dependent resistance to EM-induced apoptosis. CONCLUSION: The growth and chemo
      resistance of PC cells may be suppressed via re-expression of miR-4319 that
      inhibits Her-2 signaling.

PMID- 29633186
TI  - Enhanced recovery after surgery in gastric cancer: which are the main
      achievements from the Italian experience?
AB  - In the last years, the concept of 'enhanced recovery after surgery' (ERAS) has
      become a routine in the perioperative care of patients undergoing colorectal
      resection. The application of ERAS programs in gastric surgery had a more
      difficult penetration into clinical practice, mainly for the introduction of
      radical changes in the traditional postoperative management. The aim of the study
      was to analyze the rate of compliance to a standardized ERAS protocol in
      different Italian centers and evaluate the results in terms of postoperative
      outcomes. From April 2015 to July 2017, a prospective observational study was
      conducted among seven centers participating in the Italian Group for Research for
      Gastric Cancer (GIRCG), in patient candidates to elective gastrectomy for cancer.
      A standardized ERAS perioperative protocol was approved by all centers.
      Compliance to the protocol was then evaluated and postoperative outcomes
      (morbidity and mortality rate, duration of hospital stay and readmission rate)
      were analyzed. Two-hundred and seventy unselected patients operated on for
      gastric cancer were enrolled. The median age was 73 years; 40.4% of patients were
      female; 24.1% had a nutritional risk score >= 3. Perioperative chemotherapy was
      used in 23.7% of cases. Total gastrectomy was performed in 57.4% of patients;
      minimally invasive approach was adopted in 28.1% of patients. Adherence to the
      protocol varied between 23 and 88% for single items. It was quite low for pre-
      and intraoperative items, mainly for items related to nutritional care.
      Postoperative complications occurred in 35.5% of patients, mortality was 0.7%.
      Median length of hospital stay was 8 days (range 4-72) and the readmission rate
      was 6.3%. There is a growing attention on the implementation of ERAS protocol for
      gastric cancer surgery, but several elements of this protocol are still not
      routinely adopted, among them items regarding nutritional care.

PMID- 29633187
TI  - Lycoplanines B-D, Three Lycopodium Alkaloids from Lycopodium complanatum.
AB  - A novel C17N Lycopodium alkaloid (LA), lycoplanine B (1), containing an unusual
      formyl group, along with two new LAs, lycoplanines C (2) and D (3), were isolated
      from the whole plant of Lycopodium complanatum. Their structures were elucidated
      by extensive NMR techniques, including 1D- and 2D-NMR experiments, as well as
      comparing their spectral data with those of the known analogues. A possible
      biogenetic pathway for 1 was also proposed.

PMID- 29633190
TI  - Fractionation and leachability of Fe, Zn, Cu and Ni in the sludge from a sulphate
      reducing bioreactor treating metal-bearing wastewater.
AB  - This work presents and discusses experimental results on the characterisation and
      metal leaching potential of a biogenic, metal-rich sulphidic sludge, generated in
      a sulphate-reducing bioreactor, operated to treat acidic synthetic solutions
      bearing Fe, Zn, Ni and Cu. The sustainability of the metal removal bioprocess
      strongly depends on the fate of the sludge. To propose appropriate management
      practices, a detailed characterisation of the sludge is necessary. The
      granulometry, chemical composition and mineralogy of the sludge were initially
      determined. The mobility of the metals was assessed via a modified Tessier
      experimental procedure. The leachability of the sludge metal content was
      determined via a standard compliance method (EN 12457-2) and experiments designed
      to evaluate the effect of pH and time on metal leaching from the sludge. The
      sludge metal content sums up to 69.5% dw, namely iron (14.8%), zinc (18.7%),
      nickel (17.7%) and copper (18.2%) and, based on the criteria set by European
      Union, the sludge is characterised as hazardous and inappropriate for landfilling
      without any pretreatment. The sludge consists mainly of very fine poorly
      crystalline aggregates of Fe, Zn, Cu and Ni sulphides. The fine grain size, the
      poorly crystalline structure and the oxidation of sulphide upon exposure to
      water/air render the high metal content of the sludge recoverable.

PMID- 29633191
TI  - Effects of selected synthetic insecticides on the total and differential
      populations of circulating haemocytes in adults of the red cotton stainer bug
      Dysdercus koenigii (Fabricius) (Hemiptera: Pyrrhocoridae).
AB  - Red cotton bug, Dysdercus koenigii (Hemiptera: Pyrrhocoridae), has become the
      major insect pest of various crops, including cotton, and thereby reducing the
      yield qualitatively and quantitatively and synthetic insecticides belonging to
      different groups are the major control agents for such insect pests. A laboratory
      experiment was carried out to evaluate the effect of different conventional
      insecticides, i.e., imidacloprid, deltamethrin, lambda cyhalothrin, gamma
      cyhalothrin and cyfluthirn on haemocytes of D. koenigii. The individuals were
      exposed to insecticides separately and data was recorded after 30 and 60 min of
      the exposure. The findings of current study depicted chlorpyrifos to be more
      effective and significant alterations in total haemocyte counts and differential
      haemocyte counts were observed in the cyfluthirn treated D. koenigii. In addition
      to this, cell structure was also disrupted as an immune response. Similar studies
      would also be helpful to understand the defence mechanisms of insects against the
      xenobiotics which will help to device efficient management tools for D. koenigii.

PMID- 29633188
TI  - Antitumor Research on Artemisinin and Its Bioactive Derivatives.
AB  - Cancer is the leading cause of human death which seriously threatens human life.
      The antimalarial drug artemisinin and its derivatives have been discovered with
      considerable anticancer properties. Simultaneously, a variety of target-selective
      artemisinin-related compounds with high efficiency have been discovered. Many
      researches indicated that artemisinin-related compounds have cytotoxic effects
      against a variety of cancer cells through pleiotropic effects, including
      inhibiting the proliferation of tumor cells, promoting apoptosis, inducing cell
      cycle arrest, disrupting cancer invasion and metastasis, preventing angiogenesis,
      mediating the tumor-related signaling pathways, and regulating tumor
      microenvironment. More importantly, artemisinins demonstrated minor side effects
      to normal cells and manifested the ability to overcome multidrug-resistance which
      is widely observed in cancer patients. Therefore, we concentrated on the new
      advances and development of artemisinin and its derivatives as potential
      antitumor agents in recent 5 years. It is our hope that this review could be
      helpful for further exploration of novel artemisinin-related antitumor agents.

PMID- 29633189
TI  - Adenovirus and rotavirus recovery from a treated effluent through an optimized
      skimmed-milk flocculation method.
AB  - Sewage treatment may be insufficient for the complete removal of enteric viruses,
      such as human adenoviruses (HAdV) and group A rotavirus (RVA). The differences in
      the efficiency of the treatment methodologies used may interfere with the
      detection of these viruses. The objective of this study was to optimize a skimmed
      milk flocculation technique for the recovery of HAdV and RVA in the samples of
      treated effluent. The treated effluent collected at the wastewater treatment
      plant (WWTP) was processed via four protocols including modifications in the
      initial centrifugation step and the final concentration of skimmed-milk. The
      viral load and recovery rate were determined by quantitative PCR TaqMan(r)
      System. The highest recovery rates of HAdV, RVA, and bacteriophage PP7 (internal
      control process) were obtained when the concentration of skimmed-milk was doubled
      and no centrifugation step was used for the sample clarification. The optimized
      protocol was assessed in a field study conducted with 24 treated effluent samples
      collected bi-monthly during 2015. HAdV and RVA were detected in 50.0% (12/24) and
      33.3% (08/24) of the samples tested, respectively, throughout the year, without
      seasonal variation (p > 0.05). This study corroborates the use of the organic
      flocculation method for virus recovery in environmental samples with the
      adaptation of the protocols to different aquatic matrices.

PMID- 29633192
TI  - Ongoing environmental monitoring and assessment of the long-term impacts of the
      February 2014 radiological release from the waste isolation pilot plant.
AB  - Three years ago, the Waste Isolation Pilot Plant (WIPP) experienced its first
      minor accident involving a radiological release. Late in the evening on February
      14, 2014, a waste container in the repository underwent a chemical reaction that
      caused the container to overheat and breach, releasing its contents into the
      underground. Following a lengthy recovery process, the facility recently resumed
      waste disposal operations. The accident released significant levels of
      radioactivity into the disposal room and adjacent exhaust drifts, and although no
      one was present in the underground at the time of the release, a total of 22
      workers tested positive for very low level of radiation, presumably from some of
      the radioactive material that was released above ground through a small leak in
      the HEPA filtration system. The dominant radionuclides released were 241Am and
      239 + 240Pu in a ratio that matched the content of the drum from Los Alamos
      National Laboratory (LANL) that was eventually identified as the breached
      container. From the air particulate monitoring and plume modeling, it was
      concluded that the dose, at the nearest location accessible to the general
      public, from this radiation release event would have been less than 0.01 mSv (< 1
      mrem/year). This level is well below the 0.1 mSv/year (10 mrem/year) regulatory
      limit for DOE facilities established by the US Environmental Protection Agency
      (EPA).While no long-term impacts to public health or the environment are expected
      as a result of the WIPP radiation release, the limited ventilation and residual
      contamination levels in the underground are still a concern and pose a major
      challenge for the full recovery of WIPP. This article provides an up-to-date
      overview of environmental monitoring results through the WIPP recovery and an
      estimate of the long-term impacts of the accident on the natural and human
      environment.

PMID- 29633193
TI  - Exposure to 2,4-dichlorophenoxyacetic acid induced PPARbeta-dependent disruption
      of glucose metabolism in HepG2 cells.
AB  - 2,4-Dichlorophenoxyacetic acid is one of the most widely used herbicides. Its
      impact on health is increasingly attracting great attentions. This study aimed to
      investigate the effect of 2,4-dichlorophenoxyacetic acid on glucose metabolism in
      HepG2 cells and the underlying mechanism. After 24 h exposure to 2,4
      dichlorophenoxyacetic acid, glycogen was measured by PAS staining and glucose by
      ELISA in HepG2 cells. The expression of genes involved in glucose metabolism was
      measured by real-time PCR, Western blotting, and immunofluorescence. HepG2 cells
      presented more extracellular glucose consumption and glycogen content after
      exposed to 2,4-dichlorophenoxyacetic acid. Expression of gluconeogenesis-related
      genes, FoxO1, and CREB is significantly elevated. Moreover, PPARbeta was up
      regulated dose-dependently. SiRNA knockdown of PPARbeta completely rescued the
      increase of glycogen accumulation and glucose uptake, and the up-regulation of
      FOXO1 and CREB expression. Our findings propose novel mechanisms that 2,4
      dichlorophenoxyacetic acid causes glucose metabolism dysfunction through PPARbeta
      in HepG2 cells.

PMID- 29633194
TI  - Effluent concentration and removal efficiency of nine heavy metals in secondary
      treatment plants in Shanghai, China.
AB  - Wastewater treatment plants (WWTPs) are the most common form of industrial and
      municipal wastewater control. To evaluate the performance of wastewater treatment
      and the potential risk of treated wastewater to aquatic life and human health,
      the influent and effluent concentrations of nine toxic metals were determined in
      12 full-scale WWTPs in Shanghai, China. The performance was evaluated based on
      national standards for reclamation and aquatic criteria published by US EPA, and
      by comparison with other full-scale WWTPs in different countries. Potential
      sources of heavy metals were recognized using partial correlation analysis,
      hierarchical clustering, and principal component analysis (PCA). Results
      indicated significant treatment effect on As, Cd, Cr, Cu, Hg, Mn, Pb, and Zn. The
      removal efficiencies ranged from 92% (Cr) to 16.7% (Hg). The results indicated
      potential acute and/or chronic effect of Cu, Ni, Pb, and Zn on aquatic life and
      potential harmful effect of As and Mn on human health for the consumption of
      water and/or organism. The results of partial correlation analysis, hierarchical
      clustering based on cosine distance, and PCA, which were consistent with each
      other, suggested common source of Cd, Cr, Cu, and Pb and common source of As, Hg,
      Mn, Ni, and Zn. Hierarchical clustering based on Jaccard similarity suggested
      common source of Cd, Hg, and Ni, which was statistically proved by Fisher's exact
      test.

PMID- 29633196
TI  - Impact of the Adalimumab Patient Support Program on Clinical Outcomes in
      Ankylosing Spondylitis: Results from the COMPANION Study.
AB  - INTRODUCTION: Adalimumab (ADA) is a tumor necrosis factor (TNF)-alpha inhibitor
      indicated for the treatment of inflammatory autoimmune diseases, including
      ankylosing spondylitis (AS). Patients receiving ADA in Canada are eligible to
      enroll in the AbbVie CareTM patient support program (AC-PSP), which provides
      personalized services, including care coach calls (CCCs). We estimated the
      likelihood of controlled disease in a cohort of AS patients treated with ADA
      enrolled in the AC-PSP and who received CCCs versus those who did not. METHODS: A
      longitudinal analysis using de-identified aggregate-level data collected through
      the AC-PSP was performed. A probabilistic matching algorithm was used to link
      patient-level records from the AC-PSP database to records from the QuintilesIMS
      longitudinal prescription transactions database. Patients were indexed on the
      date of their first prescription of ADA between January 2010 and October 2015.
      The AC-PSP database included patient assessments of the Bath Ankylosing
      Spondylitis Disease Activity Index (BASDAI), a measure of disease activity.
      Eligible patients had a baseline BASDAI assessment performed between 90 days
      before and 30 days after the index date, and a follow-up BASDAI assessment 6-18
      months later. Poisson regression was used to estimate the adjusted relative risk
      (RR) of controlled disease (BASDAI < 4) at the time of follow-up, comparing
      patients who received CCCs with those who did not. RESULTS: In total 249 AS
      patients met eligibility criteria, and 123 (49%) received CCCs. Of the 249
      patients, 184 (74%) had controlled disease (BASDAI < 4) at follow-up assessment,
      98 (80%) in the CCC group and 86 (68%) in the no CCC group. Multivariable
      regression analysis demonstrated a 23% increased likelihood of controlled disease
      in patients who received CCCs relative to those who did not (RR = 1.23; 95%
      confidence interval, 1.06-1.42; p = 0.0055). CONCLUSION: AS patients receiving
      tailored services through the AC-PSP in the form of CCCs have an increased
      likelihood of controlled disease within 6-18 months. FUNDING: AbbVie.

PMID- 29633197
TI  - Cost-effectiveness Analysis of Golimumab in the Treatment of Non-Radiographic
      Axial Spondyloarthritis in Scotland.
AB  - INTRODUCTION: The aim of this study is to assess the cost-effectiveness of
      golimumab for the treatment of non-radiographic axial spondyloarthritis (nr
      axSpA) vs. conventional therapy and other tumor necrosis factor inhibitors from
      the Scottish payer perspective. METHODS: A model comprising a short-term decision
      tree and a long-term Markov model was developed to compare cost-effectiveness
      (incremental costs per quality-adjusted life-year [QALY]) for patients in
      Scotland with nr-axSpA treated by conventional therapy, adalimumab, certolizumab
      pegol, etanercept, or golimumab for a lifetime period. A network meta-analysis
      (NMA) was conducted to identify clinical and safety data for treatments and
      synthesize the available evidence into relative treatment effects between
      comparators. The probability of patients achieving an Assessment of
      SpondyloArthritis International Society 20/40% response criteria (ASAS20/ASAS40)
      or a 50% improvement in Bath Ankylosing Spondylitis Disease Activity Index score
      (BASDAI50) at week 12 was obtained from the NMA for each of the comparators.
      Baseline health state utilities were based on the EQ-5D questionnaire collected
      in the golimumab GO-AHEAD study. The cost of treatment was calculated based on
      drug acquisition, drug administration, and initiation/monitoring costs. RESULTS:
      Golimumab resulted in an increase of 2.06 QALYs and additional cost of L39,770
      compared with conventional therapy. Incremental cost per QALY gained was L19,280
      for golimumab, which was lower than adalimumab (L19,737), etanercept (L20,089),
      and higher than certolizumab pegol (L18,710). Golimumab remained cost-effective
      throughout a range of sensitivity analyses where key assumptions were tested.
      CONCLUSIONS: From a Scottish perspective, golimumab was a cost-effective
      treatment for nr-axSpA compared with conventional therapy at a willingness-to-pay
      threshold of L30,000 per QALY. FUNDING: Merck & Co., Inc.

PMID- 29633198
TI  - The influence of emotional stimuli on the oculomotor system: A review of the
      literature.
AB  - In the past decade, more and more research has been investigating oculomotor
      behavior in relation to attentional selection of emotional stimuli. Whereas
      previous research on covert emotional attention demonstrates contradictory
      results, research on overt attention clearly shows the influence of emotional
      stimuli on attentional selection. The current review highlights studies that have
      used eye-movement behavior as the primary outcome measure in healthy populations
      and focusses on the evidence that emotional stimuli-in particular, threatening
      stimuli-affect temporal and spatial dynamics of oculomotor programming. The most
      prominent results from these studies indicate that attentional selection of
      threatening stimuli is under bottom-up control. Moreover, threatening stimuli
      seem to have the greatest impact on oculomotor behavior through biased processing
      via the magnocellular pathway. This is consistent with an evolutionary account of
      threat processing, which claims a pivotal role for a subcortical network
      including pulvinar, superior colliculus, and amygdala. Additionally, I suggest a
      neurobiological model that considers possible mechanisms by which emotional
      stimuli could affect oculomotor behavior. The present review confirms the
      relevance of eye-movement measurements in relation to researching emotion in
      order to elucidate processes involved in emotional modulation of visual and
      attentional selection.

PMID- 29633200
TI  - Next-Generation Live-Cell Microarray Technologies.
AB  - Over the last decades the application of cell-based assays and in vitro cell
      culture systems has fundamentally transformed our understanding of biological
      functions on a cellular and organism level. The resulting ubiquitous usage of
      cell-based assays in today's scientific world has therefore generated a need for
      advanced in vitro diagnostic systems. This increased demand has further led to
      the development of miniaturized live-cell microarrays for biomedical applications
      including high-throughput screening tools and microfluidic systems. The greatest
      benefit of miniaturized cell analysis systems is the ability to provide
      quantitative data in real time with high reliability and sensitivity, which are
      key parameters for any cell-based assay. An additional advantage of live-cell
      microarrays is their inherent capability for large-scale screening of single
      cells, multicell populations, as well as spheroids.

PMID- 29633201
TI  - Cell-Based Microarrays Using Superhydrophobic Platforms Patterned with Wettable
      Regions.
AB  - The use of patterned platforms to print cellular arrays enables the high
      throughput study of cell behavior under a multitude of different conditions. This
      rapid, cost-saving and systematic way of acquiring biologically relevant
      information has found application in diverse scientific and industrial fields. In
      an initial stage of development, platforms targeting high-throughput cellular
      studies were restricted to standard two-dimensional (2D) setups. The design of
      novel platforms compatible with three-dimensional (3D) cell culture arose after
      the elucidation of the extreme importance of culturing cells in matrices
      resembling the native extracellular matrix-cells and cell-cell interactions. This
      need for biomimetic environments has been established in fields like drug
      discovery and testing, disease model development, and regenerative medicine.
      Here, we provide a description of the processing of flat platforms based on
      wettability contrast, compatible with the high-throughput generation and study of
      cell response in 3D biomaterials, including cell-laden hydrogels and porous 3D
      scaffolds. The application of the aforementioned platforms to produce 3D
      microtissues, which may find application as tissue models for drug screening or
      as biomimetic building blocks for tissue engineering, is also addressed. In this
      chapter, a description of the steps for (1) high-throughput platform processing,
      (2) deposition of cell and biomaterial arrays, and (3) image-based results
      screening is provided.

PMID- 29633199
TI  - Psychopathic traits associated with abnormal hemodynamic activity in salience and
      default mode networks during auditory oddball task.
AB  - Psychopathy is a personality disorder accompanied by abnormalities in emotional
      processing and attention. Recent theoretical applications of network-based models
      of cognition have been used to explain the diverse range of abnormalities
      apparent in psychopathy. Still, the physiological basis for these abnormalities
      is not well understood. A significant body of work has examined psychopathy
      related abnormalities in simple attention-based tasks, but these studies have
      largely been performed using electrocortical measures, such as event-related
      potentials (ERPs), and they often have been carried out among individuals with
      low levels of psychopathic traits. In this study, we examined neural activity
      during an auditory oddball task using functional magnetic resonance imaging
      (fMRI) during a simple auditory target detection (oddball) task among 168
      incarcerated adult males, with psychopathic traits assessed via the Hare
      Psychopathy Checklist-Revised (PCL-R). Event-related contrasts demonstrated that
      the largest psychopathy-related effects were apparent between the frequent
      standard stimulus condition and a task-off, implicit baseline. Negative
      correlations with interpersonal-affective dimensions (Factor 1) of the PCL-R were
      apparent in regions comprising default mode and salience networks. These findings
      support models of psychopathy describing impaired integration across functional
      networks. They additionally corroborate reports which have implicated failures of
      efficient transition between default mode and task-positive networks. Finally,
      they demonstrate a neurophysiological basis for abnormal mobilization of
      attention and reduced engagement with stimuli that have little motivational
      significance among those with high psychopathic traits.

PMID- 29633202
TI  - 3D Plasma Nanotextured(r) Polymeric Surfaces for Protein or Antibody Arrays, and
      Biomolecule and Cell Patterning.
AB  - Plasma micro-nanotexturing is a generic technology for topographical and chemical
      modification of surfaces and their implementation in microfluidics and
      microarrays. Nanotextured surfaces with desirable chemical functionality (and
      wetting behavior) have shown excellent biomolecule immobilization and cell
      adhesion. Specifically, nanotextured hydrophilic areas show (a) strong binding of
      biomolecules and (b) strong adhesion of cells, while nanotextured
      superhydrophobic areas show null adsorption of (a) proteins and (b) cells. Here
      we describe the protocols for (a) biomolecule adsorption control on nanotextured
      surfaces for microarray fabrication and (b) cell adhesion on such surfaces. 3D
      plasma nanotextured(r) substrates are commercialized through Nanoplasmas private
      company, a spin-off of the National Centre for Scientific Research Demokritos.

PMID- 29633203
TI  - Single Cell Microarrays Fabricated by Microscale Plasma-Initiated Protein
      Patterning (MUPIPP).
AB  - Micropatterned arrays considerably advanced single cell fluorescence time-lapse
      measurements by providing standardized boundary conditions for thousands of cells
      in parallel. In these assays, cells are forced to adhere to defined
      microstructured protein islands separated by passivated, nonadhesive areas. Here
      we provide a detailed protocol on how to reproducibly fabricate high quality
      single cell arrays by microscale plasma-initiated protein patterning (MUPIPP).
      Advantages of MUPIPP arrays are the ease of preparation and the unrestricted
      choice of substrates as well as proteins. We demonstrate how the arrays enable
      the efficient measurement of single cell time trajectories using automated data
      acquisition and data analysis by example of single cell gene expression after
      mRNA transfection and time courses of single cell apoptosis. We discuss the more
      general use of the protocol for assessment of single cell dynamics with the help
      of fluorescent reporters.

PMID- 29633204
TI  - Artificial Microniche Array with Spatially Structured Biochemical Cues.
AB  - We present here a method to create arrays of microcavities that can be
      differentially coated on their bottom, side, and top with different proteins.
      These cavities range in size from single cell to multicellular aggregate. We
      provide detailed protocols to create such arrays with some variations using
      different materials and different coating proteins. The use of such cavities as
      bona fide artificial microniches to mimic cellular microenvironments has been
      already established and is referenced.

PMID- 29633205
TI  - Three-Dimensional Cell-Based Microarrays: Printing Pluripotent Stem Cells into 3D
      Microenvironments.
AB  - Cell-based microarrays are valuable platforms for the study of cytotoxicity and
      cellular microenvironment because they enable high-throughput screening of large
      sets of conditions at reduced reagent consumption. However, most of the described
      microarray technologies have been applied to two-dimensional cultures, which do
      not accurately emulate the in vivo three-dimensional (3D) cell-cell and cell
      extracellular matrix interactions.Herein, we describe the methodology for
      production of alginate- and Matrigel-based 3-D cell microarrays for the study of
      mouse and human pluripotent stem cells on two different chip-based platforms. We
      further provide protocols for on-chip proliferation/viability analysis and the
      assessment of protein expression by immunofluorescence.

PMID- 29633206
TI  - Fabrication of Biomolecule Microarrays for Cell Immobilization Using Automated
      Microcontact Printing.
AB  - Biomolecule microarrays are generally produced by conventional microarrayer,
      i.e., by contact or inkjet printing. Microcontact printing represents an
      alternative way of deposition of biomolecules on solid supports but even if
      various biomolecules have been successfully microcontact printed, the production
      of biomolecule microarrays in routine by microcontact printing remains a
      challenging task and needs an effective, fast, robust, and low-cost automation
      process. Here, we describe the production of biomolecule microarrays composed of
      extracellular matrix protein for the fabrication of cell microarrays by using an
      automated microcontact printing device. Large scale cell microarrays can be
      reproducibly obtained by this method.

PMID- 29633207
TI  - Hydrogel Printing Based on UV-Induced Projection for Cell-Based Microarray
      Fabrication.
AB  - A considerable number of studies have focused on fabrication of hydrogel
      microstructures due to its wide applications in tissue engineering, drug
      delivery, and extracellular matrix construction. Here, we introduce a hydrogel
      printing method based on UV-induced projection via a digital micromirror device
      (DMD). Arbitrary microstructures could be fabricated within few seconds (<3) by
      modulating UV projection using DMD as digital dynamic masks instead of a physical
      mask, which also offers a high degree of flexibility and repeatability.
      Furthermore, the ability of PEGDA film to hinder cell adhesion makes it possible
      to control area over which cells attach.

PMID- 29633208
TI  - Inkjet Printing for Biomedical Applications.
AB  - Inkjet printing can deposit politer volumes of a specified ink at precise
      locations on a substrate. Here we describe methods of using inkjet printing for
      cell patterning in the field of biomedical applications, either directly printing
      cells in cell media, or indirectly through printing a wax scaffold that guides
      cell orientation/attachment onto a substrate.

PMID- 29633209
TI  - High-Throughput Screening of Senescence Markers in Hematopoietic Stem Cells
      Derived from Induced Pluripotent Stem Cells.
AB  - The successful development and characterization of human induced pluripotent stem
      cells (iPSCs) provides a powerful tool to study the molecular mechanisms that
      control cell fate decisions and differentiation toward distinct lineages. Here we
      focus on the ability of donors derived iPSCs to differentiate toward
      hematopoietic progenitor cells and on the analysis of their telomere length. The
      ability to screen telomere length in individual donors is important for defining
      cellular senescence, which correlates with their differentiation potential toward
      hematopoietic lineages. We have modified iPSC culture protocol and telomere
      length analysis to suit for high throughput screening of telomere length in large
      number of individual donors. This approach can be used to demonstrate the
      heterogeneity or changes of telomere length and its shortening as an exclusion
      criterion for selection of suitable donors for future stem cell therapies.

PMID- 29633210
TI  - Primary and Stem Cell Microarrays: Application as Miniaturized Biotesting
      Systems.
AB  - The deposition of living cells on microarray surfaces can be used to create
      physiologically relevant architecture in vitro. Such living cell microarrays
      enable the reconstruction of biological processes outside the body in a
      miniaturized format and have many advantages over traditional cell culture. The
      present protocol offers an option for the preparation and analysis of living
      primary and stem cell-based microarrays utilizing the standard microarray
      equipment (contact-free piezoelectric nanoprinter, microarray scanner), as well
      as microscopy. To produce living cell microarrays, we applied two kinds of
      mesenchymal stem cells (MSCs) isolated from umbilical cord and adipose tissue, as
      well as human umbilical vein endothelial cells (HUVECs) as model cells. We used
      live imaging microscopy for the online monitoring of cell spots in total size,
      staining of viable cells with Calcein acetoxymethyl ester (Calcein-AM) and
      treatment of MSCs with differentiation media to analyze the proliferation,
      viability, and differentiation potential of printed cells. This way, the general
      applicability of the established living cell-based microarray production was
      demonstrated.

PMID- 29633211
TI  - Fabrication of Multielectrode Arrays for Neurobiology Applications.
AB  - Substrate-integrated multielectrode arrays (MEAs) enable multisite, long-term,
      and label-free sensing and actuation of neuronal electrical signals in reduced
      cell culture models for network electrophysiology. Conventional, thin-film
      fabricated passive MEAs typically provide a few tens of electrode sites. New
      generations of active CMOS-based high-resolution arrays provide the capabilities
      of simultaneous recordings from thousands of neurons over fields of view of
      several square millimeters, yet allowing extracellular electrical imaging to be
      achieved down to the subcellular scale. In turn, such advancement in chip-based
      electrical readouts can significantly complement recently developed
      biotechnological and bimolecular techniques for neurobiology applications. Here,
      we describe (1) a simple method to fabricate passive MEAs and (2) protocols for
      preparing and growing primary rat hippocampal neuronal cultures and human iPS
      derived neurons on MEAs. The aim is to provide reliable protocols for initiating
      the reader to this technology and for stimulating their further development and
      experimental use in neurobiology.

PMID- 29633212
TI  - Rapid Prototyping of Thermoplastic Microfluidic Devices.
AB  - Microfluidic systems can be applied to develop unique tools for cell culture, low
      cost diagnostics, and precision experimentation by leveraging microscale fluid
      flow. As the field has expanded and matured, there is a need for rapid
      prototyping that is both accessible to most research groups and can readily
      translate toward scalable commercial manufacturing. Here, we describe a protocol
      that incorporates rapid computer numerical control (CNC) milling of positive
      molds, casting of a negative high-durometer silicone mold, and hot embossing to
      produce microfluidic devices composed of virtually any thermoplastic material.
      The method bypasses the need for high-precision machining of the bonding surfaces
      by using a cast acrylic stock and only milling channels, thus expanding this
      protocol to any CNC platform This technique represents a versatile, high-fidelity
      prototyping method that enables fast turnaround of prototype devices in a
      standard laboratory setting, while offering scalability for commercial
      manufacturing.

PMID- 29633213
TI  - Fabrication of Biomolecule Microarrays Using Rapid Photochemical Surface
      Patterning in Thiol-Ene-Based Microfluidic Devices.
AB  - In many biochip applications, it is advantageous to be able to immobilize
      biomolecules at specific locations on the surface of solid supports. In this
      protocol, we describe a photochemical surface patterning procedure based on thiol
      ene/yne photochemistry which allows for the simple and rapid selective patterning
      of biomolecules on thiol-ene solid supports. We describe the preparation of solid
      supports which are required for the immobilization, including porous monoliths,
      as well as two different immobilization schemes based on biotin-streptavidin
      interactions and covalent linkage via free amino groups respectively.

PMID- 29633214
TI  - Fabrication and Operation of Microfluidic Hanging-Drop Networks.
AB  - The hanging-drop network (HDN) is a technology platform based on a completely
      open microfluidic network at the bottom of an inverted, surface-patterned
      substrate. The platform is predominantly used for the formation, culturing, and
      interaction of self-assembled spherical microtissues (spheroids) under precisely
      controlled flow conditions. Here, we describe design, fabrication, and operation
      of microfluidic hanging-drop networks.

PMID- 29633216
TI  - Establishment of Microfluidic Spheroid Cultures for Biomedical Applications.
AB  - Multicellular spheroid is a three-dimensional (3D) cell culture model that mimics
      cancer tumor environment. Its widespread use for anticancer therapy evaluation is
      nowadays limited by accessibility of 3D compatible assays. Here, a microfluidic
      system for spheroid formation, culture and analysis is presented. The system is
      compatible with standard microplate readers. The microfluidic chip enables long
      term 3D cell culture and in situ monitoring of cellular viability. Moreover,
      design of the assay enables observation of delayed type of toxicity or
      application of repeated doses of a drug.

PMID- 29633215
TI  - A Microfluidic Droplet Array System for Cell-Based Drug Combination Screening.
AB  - In the last few decades, drug combination therapy has been widely applied in
      oncology and in other complex diseases. Due to its potential advantage of lower
      drug toxicity and higher therapeutic efficacy, drug combination treatment has
      been more and more studied in fundamental labs and pharmacy companies. In this
      chapter, we report cell-based drug combination screening using a microfluidic
      droplet system based on a sequential operation droplet array (SODA) technique. In
      this system, an oil-covered two-dimensional droplet array chip was used as the
      platform for cell culture and analysis. This chip was fixed in an x-y-z
      translation stage under control of a computer program. A tapered capillary
      connected with a syringe pump was coupled with the droplet array chip to achieve
      multiple droplet manipulations including liquid metering, aspirating, depositing,
      mixing, and transferring. Complex multistep operations for drug combination
      screening involving long-term cell culture, medium changing, schedule-dependent
      drug dosage and stimulation, and cell viability testing were achieved in parallel
      using the present system. The drug consumption for each screening test was
      substantially decreased to 5 ng-5 MUg, corresponding to 10- to 1000-fold
      reductions compared with traditional drug screening systems with 96- or 384-well
      plates.

PMID- 29633217
TI  - Capillary Pinning Assisted Patterning of Cell-Laden Hydrogel Microarrays in
      Microchips.
AB  - We present a capillary pinning technique that gives complete control on the local
      patterning of hydrogel structures in closed microchips. The technique relies on
      selective trapping of liquids at predefined locations in a microchip using
      capillary barriers. In selective patterning, the abrupt expansion in the cross
      sectional geometry of a microchannel at capillary barriers results in a confined
      advancement of the liquid-air meniscus. This protocol describes a detailed
      procedure to design and fabricate microarrays of different hydrogel types,
      fabricated with photopolymerization or thermogelation. The process can be
      subdivided into two parts. First, a PDMS microchip containing microfeatures with
      customized patterns is fabricated. Second, the microchip is filled with a
      hydrogel precursor to be cross-linked by either photopolymerization or
      thermogelation. The production of the microchip takes approximately 2 days,
      depending on the substrate selection. Preparation of the hydrogel solutions takes
      1-2 h, whereas the patterning and reaction to cross-link the hydrogels is
      completed in a few minutes.

PMID- 29633218
TI  - Oxygen-Generating Photocrosslinkable Hydrogel.
AB  - Providing sufficient amount of oxygen to the cells is a critical issue since the
      lack of adequate oxygen leads to cell death and tissue necrosis. Therefore, there
      is a vital need to design and fabricate oxygen-generating biomaterials to
      mitigate hypoxia-induced cell death in engineered tissues. Here, we report the
      fabrication of an oxygen-generating hydrogel by incorporating calcium peroxide
      (CPO) into the methacrylated gelatin (GelMA) structure using photocrosslinking
      process. A sustainable release of oxygen could be provided from CPO-GelMA
      hydrogel over a period of 5 days under hypoxic conditions (1% O2).

PMID- 29633219
TI  - A Self-Assembled Antifouling Nano-Biointerface for the Generation of Spheroids.
AB  - Several techniques have been established over the last decades to produce three
      dimensional (3D) cellular spheroids and each method has its advantages and
      limitations. The unique self-assembly properties of surface layer (S-layer)
      proteins have already been applied to a broad range of life science applications.
      The bacterial S-layer protein SbpA displays a strong antifouling behavior when
      recrystallized on planar surfaces and offers the opportunity to induce 3D cell
      aggregation. In this chapter, an S-layer nanointerface is presented as novel
      ultralow attachment material for the formation of functional spheroids of
      reproducible sizes. The system is compatible with standard microwell plates and
      enables long-term 3D cell culture and in situ monitoring of cellular viability.
      Moreover, this facile and stable biointerface has potential for use in toxicity
      screening assays and represents an alternative to conventional materials like
      polyethylene glycol (PEG), agarose, or hydrogel surfaces.

PMID- 29633220
TI  - Spectroscopic Identification of the Carbyne Hydride Structure of the
      Dehydrogenation Product of Methane Activation by Osmium Cations.
AB  - The present work explores the structures of species formed by dehydrogenation of
      methane (CH4) and perdeuterated methane (CD4) by the 5d transition metal cation
      osmium (Os+). Using infrared multiple photon dissociation (IRMPD) action
      spectroscopy and density functional theory (DFT), the structures of the
      [Os,C,2H]+ and [Os,C,2D]+ products are explored. This study complements previous
      work on the related species formed by dehydrogenation of methane by four other 5d
      transition metal cations (M+ = Ta+, W+, Ir+, and Pt+). Osmium cations are formed
      in a laser ablation source, react with methane pulsed into a reaction channel
      downstream, and the resulting products spectroscopically characterized through
      photofragmentation using the Free-Electron Laser for IntraCavity Experiments
      (FELICE) in the 300-1800 cm-1 range. Photofragmentation was monitored by the loss
      of H2/D2. Comparison of the experimental spectra and DFT calculated spectra leads
      to identification of the ground state carbyne hydride, HOsCH+ (2A') as the
      species formed, as previously postulated theoretically. Further, a full
      description of the systematic spectroscopic shifts observed for deuterium
      labeling of these complexes, some of the smallest systems to be studied using
      IRMPD action spectroscopy, is achieved. A full rotational contour analysis
      explains the observed linewidths as well as the observation of doublet structures
      in several bands, consistent with previous observations for HIrCH+ (2A').
      Graphical Abstract ?.

PMID- 29633221
TI  - Insight into Identification of Acinetobacter Species by Matrix-Assisted Laser
      Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF MS) in the
      Clinical Laboratory.
AB  - Currently, the capability of identification for Acinetobacter species using MALDI
      TOF MS still remains unclear in clinical laboratories due to certain elusory
      phenomena. Thus, we conducted this research to evaluate this technique and reveal
      the causes of misidentification. Briefly, a total of 788 Acinetobacter strains
      were collected and confirmed at the species level by 16S rDNA and rpoB
      sequencing, and subsequently compared to the identification by MALDI-TOF MS using
      direct smear and bacterial extraction pretreatments. Cluster analysis was
      performed based on the mass spectra and 16S rDNA to reflect the diversity among
      different species. Eventually, 19 Acinetobacter species were confirmed, including
      6 species unavailable in Biotyper 3.0 database. Another novel species was
      observed, temporarily named A. corallinus. The accuracy of identification for
      Acinetobacter species using MALDI-TOF MS was 97.08% (765/788), regardless of
      which pretreatment was applied. The misidentification only occurred on 3 A.
      parvus strains and 20 strains of species unavailable in the database. The
      proportions of strains with identification score >= 2.000 using direct smear and
      bacterial extraction pretreatments were 86.04% (678/788) and 95.43% (752/788),
      chi2 = 41.336, P < 0.001. The species similar in 16 rDNA were discriminative from
      the mass spectra, such as A. baumannii & A. junii, A. pittii & A. calcoaceticus,
      and A. nosocomialis & A. seifertii. Therefore, using MALDI-TOF MS to identify
      Acinetobacter strains isolated from clinical samples was deemed reliable.
      Misidentification occurred occasionally due to the insufficiency of the database
      rather than sample extraction failure. We suggest gene sequencing should be
      performed when the identification score is under 2.000 even when using bacterial
      extraction pretreatment. Graphical Abstract ?.

PMID- 29633222
TI  - Establishment of a Charge Reversal Derivatization Strategy to Improve the
      Ionization Efficiency of Limaprost and Investigation of the Fragmentation
      Patterns of Limaprost Derivatives Via Exclusive Neutral Loss and Survival Yield
      Method.
AB  - Sensitivity is generally an issue in bioassays of prostaglandins and their
      synthetic analogs due to their extremely low concentration in vivo. To improve
      the ionization efficiency of limaprost, an oral prostaglandin E1 (PGE1) synthetic
      analog, we investigated a charge reversal derivatization strategy in electrospray
      ionization mass spectrometry (ESI-MS). We established that the cholamine
      derivative exhibits much greater signal intensity in the positive-ion mode
      compared with limaprost in the negative ion mode. Collision-induced dissociation
      (CID) involved exclusive neutral mass loss and positive charge migration to form
      stable cationic product ions with the positive charge on the limaprost residue
      rather than on the modifying group. This has the effect of maintaining the
      efficiency and specificity of multiple reaction monitoring (MRM) and avoiding
      cross talk. CID fragmentation patterns of other limaprost derivatives allowed us
      to relate the dissociation tendency of different neutral leaving groups to an
      internal energy distribution scale based on the survival yield method. Knowledge
      of the energy involved in the production of stabilized positive ions will
      potentially assist the selection of suitable derivatization reagents for the
      analysis of a wide variety of lipid acids. Graphical Abstract ?.

PMID- 29633223
TI  - Comprehensive Characterization of Swine Cardiac Troponin T Proteoforms by Top
      Down Mass Spectrometry.
AB  - Cardiac troponin T (cTnT) regulates the Ca2+-mediated interaction between myosin
      thick filaments and actin thin filaments during cardiac contraction and
      relaxation. cTnT is released into the blood following injury, and increased serum
      levels of the protein are used clinically as a biomarker for myocardial
      infarction. Moreover, mutations in cTnT are causative in a number of familial
      cardiomyopathies. With the increasing use of large animal (swine) model to
      recapitulate human diseases, it is essential to characterize species-dependent
      protein sequence variants, alternative RNA splicing, and post-translational
      modifications (PTMs), but challenges remain due to the incomplete database and
      lack of validation of the predicted splicing isoforms. Herein, we integrated top
      down mass spectrometry (MS) with online liquid chromatography (LC) and
      immunoaffinity purification to comprehensively characterize miniature swine cTnT
      proteoforms, including those arising from alternative RNA splicing and PTMs. A
      total of seven alternative splicing isoforms of cTnT were identified by LC/MS
      from swine left ventricular tissue, with each isoform containing un
      phosphorylated and mono-phosphorylated proteoforms. The phosphorylation site was
      localized to Ser1 for the mono-phosphorylated proteoforms of cTnT1, 3, 4, and 6
      by online MS/MS combining collisionally activated dissociation (CAD) and electron
      transfer dissociation (ETD). Offline MS/MS on Fourier-transform ion cyclotron
      resonance (FT-ICR) mass spectrometer with CAD and electron capture dissociation
      (ECD) was then utilized to achieve deep sequencing of mono-phosphorylated cTnT1
      (35.2 kDa) with a high sequence coverage of 87%. Taken together, this study
      demonstrated the unique advantage of top-down MS in the comprehensive
      characterization of protein alternative splicing isoforms together with PTMs.
      Graphical Abstract ?.

PMID- 29633226
TI  - Bringing Healthy Retail to Urban "Food Swamps": a Case Study of CBPR-Informed
      Policy and Neighborhood Change in San Francisco.
AB  - In urban "food swamps" like San Francisco's Tenderloin, the absence of full
      service grocery stores and plethora of corner stores saturated with tobacco,
      alcohol, and processed food contribute to high rates of chronic disease. We
      explore the genesis of the Tenderloin Healthy Corner Store Coalition, its
      relationship with health department and academic partners, and its contributions
      to the passage and implementation of a healthy retail ordinance through community
      based participatory research (CBPR), capacity building, and advocacy. The healthy
      retail ordinance incentivizes small stores to increase space for healthy foods
      and decrease tobacco and alcohol availability. Through Yin's multi-method case
      study analysis, we examined the partnership's processes and contributions to the
      ordinance within the framework of Kingdon's three-stage policymaking model. We
      also assessed preliminary outcomes of the ordinance, including a 35% increase in
      produce sales and moderate declines in tobacco sales in the first four stores
      participating in the Tenderloin, as well as a "ripple effect," through which non
      participating stores also improved their retail environments. Despite challenges,
      CBPR partnerships led by a strong community coalition concerned with bedrock
      issues like food justice and neighborhood inequities in tobacco exposure may
      represent an important avenue for health equity-focused research and its
      translation into practice.

PMID- 29633224
TI  - Rapid Quantification of 25-Hydroxyvitamin D3 in Human Serum by Matrix-Assisted
      Laser Desorption/Ionization Mass Spectrometry.
AB  - LC-MS/MS is widely utilized today for quantification of vitamin D in biological
      fluids. Mass spectrometric assays for vitamin D require very careful method
      optimization for precise and interference-free, accurate analyses however. Here,
      we explore chemical derivatization and matrix-assisted laser
      desorption/ionization (MALDI) as a rapid alternative for quantitative measurement
      of 25-hydroxyvitamin D3 in human serum, and compare it to results from LC-MS/MS.
      The method implemented an automated imaging step of each MALDI spot, to locate
      areas of high intensity, avoid sweet spot phenomena, and thus improve precision.
      There was no statistically significant difference in vitamin D quantification
      between the MALDI-MS/MS and LC-MS/MS: mean +/- standard deviation for MALDI-MS
      29.4 +/- 10.3 ng/mL-versus LC-MS/MS-30.3 +/- 11.2 ng/mL (P = 0.128)-for the sum
      of the 25-hydroxyvitamin D epimers. The MALDI-based assay avoided time-consuming
      chromatographic separation steps and was thus much faster than the LC-MS/MS
      assay. It also consumed less sample, required no organic solvents, and was
      readily automated. In this proof-of-concept study, MALDI-MS readily demonstrated
      its potential for mass spectrometric quantification of vitamin D compounds in
      biological fluids. Graphical Abstract ?.

PMID- 29633227
TI  - The Association between Incarceration and Transactional Sex among HIV-infected
      Young Men Who Have Sex with Men in the United States.
AB  - Criminal justice practices in the USA disproportionately affect sexual and
      racial/ethnic minority men, who are at higher risk of incarceration. Previous
      research demonstrates associations between incarceration and sexual risk
      behaviors for men who have sex with men (MSM). However, little of this work
      focuses on young MSM (YMSM), particularly HIV-infected YMSM, despite nearly one
      third reporting engagement in sexual risk behaviors, such as transactional sex.
      We therefore explored the association between incarceration and transactional sex
      among HIV-infected YMSM. We recruited 97 HIV-infected YMSM across 14 clinical
      sites in urban centers from August 2015 to February 2016. We used multivariate
      logistic regression to examine the relationship between incarceration and
      transactional sex among YMSM. The majority was 24 years old (78%) and
      racial/ethnic minority (95%); over half were not in school and reported an annual
      income of < $12,000. In the multivariate model, having ever been incarcerated
      (aOR = 3.20; 95% CI 1.07-9.63) was independently associated with a history of
      transactional sex. Being 24 years vs. younger (aOR = 9.68; 95% CI 1.42-65.78) and
      having ever been homeless (aOR = 3.71, 95% CI 1.18-11.65) also remained
      independently associated with a history of transactional sex. This analysis fills
      a gap in the literature by examining the relationship between incarceration and
      transactional sex among HIV-infected YMSM. Facilitating youths' engagement with
      social services available in their HIV clinic may serve as a key strategy in
      promoting health. Public health efforts need to address social-structural factors
      driving disproportionate rates of arrest and incarceration and related harms
      among this population.

PMID- 29633229
TI  - Development of a serum neutralization assay to detect Pteropine Orthoreovirus
      Indonesia/2010 neutralizing antibodies.
AB  - Pteropine Orthoreoviruses (PRVs) are fusogenic bat-borne orthoreoviruses that
      cause flu-like upper respiratory tract infections in humans. The presence of this
      group of viruses in bats and humans has been well documented in areas where their
      biological reservoirs - fruit bats (family Pteropodidae) - live densely. In the
      present study, a serum neutralization (SN) assay to detect neutralizing
      antibodies against PRV Indonesia/2010 isolate was set up and used to assess the
      seroprevalence of this virus in Italian domestic animals. The new developed assay
      was able of detecting PRV neutralizing antibodies in the hyper-immune polyclonal
      serum produced in rabbits (titer of 1:160). The negative serum was negative at
      all tested dilutions. No cross-reactions have been evidenced neither against
      reference MRVs nor against their respective hyper-immune sera. Eight hundred and
      fifty-three serum samples collected from 524 bovines, 271 small ruminants, and 58
      horses (all used as sentinel animals in the Bluetongue and West Nile disease
      National surveillance program) were also tested with the new developed SN assay.
      According to the results of this survey, neither PRV nor PRV cross- reacting
      viruses antibodies have been demonstrated in Italian domestic animals. However,
      the new developed SN assay could be a very valuable diagnostic tool to detect
      infection in animals and humans.

PMID- 29633228
TI  - Positive Effectiveness of Tafamidis in Delaying Disease Progression in
      Transthyretin Familial Amyloid Polyneuropathy up to 2 Years: An Analysis from the
      Transthyretin Amyloidosis Outcomes Survey (THAOS).
AB  - INTRODUCTION: The effectiveness of tafamidis for the treatment of transthyretin
      familial amyloid polyneuropathy (TTR-FAP) was evaluated using data from the
      Transthyretin Amyloidosis Outcomes Survey (THAOS) registry. METHODS: Subjects
      receiving tafamidis (n = 252) were compared with untreated subjects in a non
      randomized, matched cohort analysis. Subjects were matched with up to four
      untreated controls by genetic mutation, region of birth, and mean treatment
      propensity score. RESULTS: The matched, treated sample consisted predominantly of
      subjects with the Val30Met genotype (92.5%), from Portugal, and with a mean age
      of 40.4 years. Over the course of the 2-year follow-up period, subjects treated
      with tafamidis showed significantly less deterioration on the Neuropathy
      Impairment Score for Lower Limbs (p < 0.001) and its subscales (p < 0.023)
      compared with untreated subjects. There was significantly less deterioration
      among tafamidis-treated subjects compared with untreated subjects on the Norfolk
      Quality of Life scale (p < 0.001). There were no significant differences observed
      in functional (assessed by Karnofsky Performance Status Scale score) or
      nutritional (assessed by modified body mass index) status between the treated and
      untreated groups. The primary model which examined survival from baseline using
      the matched cohort was not able to yield estimates of the hazard ratio, as there
      were no deaths in the tafamidis-treated subjects. CONCLUSION: These findings
      support the results from clinical trials and strengthen evidence of the
      effectiveness of tafamidis beyond conventional clinical trials. TRIAL
      REGISTRATION: ClinicalTrials.gov: NCT00628745 FUNDING: Pfizer.

PMID- 29633230
TI  - Adverse food reactions in dogs due to antibiotic residues in pet food: a
      preliminary study.
AB  - In the last decades, adverse food reactions have increased considerably in dogs
      and cats. In this study we report on the possible onset of food intolerances
      symptoms, including otitis, diarrhoea, generalised anxiety, and dermatitis in a
      cohort of 8 dogs consuming commercial diets. All dogs received an organic chicken
      based diet for 15 days. We performed analysis of blood biochemical parameters,
      kibble composition, and oxytetracycline (OTC) serum concentration before and
      after 15 days of organic chicken-based diet supplementation. We hypothesised that
      a chronic intake of contaminated food enhanced by the presence of nanoparticle
      aggregates might be at the base of the onset of pharmacologic or idiopathic food
      intolerances. At the end of the evaluation period, an overall significant
      reduction of otitis, diarrhoea, generalised anxiety, and dermatitis was observed.
      Biochemical analyses indicate a significant increase in the alkaline phosphatase,
      from 41 to 52.5 U/L, after 15 days (**p <0.01), while a significant decrease in
      Gamma-glutamyl transferase and urea, from 9.37 to 6.25 U/L and from 32.13 +/-
      8.72 to 22.13 +/- 7.8 mg/dL, respectively, was observed (*p <0.05). A significant
      decrease, from 0.22 to 0.02 MUg/mL, in mean OTC serum concentration was also
      observed (**p <0.01). Composition analysis revealed the presence of OTC, calcium,
      aluminium, silicon, and phosphorous nanoparticle aggregates. Further research on
      a wider sample size would help to confirm the hypothesis proposed here.

PMID- 29633231
TI  - Reperfusion treatment in acute myocardial infarction in elderly patients.
AB  - In this paper the current knowledge of reperfusion therapy in elderly patients
      with an ST-segment elevation acute myocardial infarction (STEMI) is summarised.
      Placebo-controlled trials of fibrinolytic agents, direct comparative trials of
      fibrinolytic agents and antithrombotic co-therapies, and randomised trials of
      primary percutaneous coronary intervention (PCI) versus fibrinolytic therapy as
      well as registries are briefly reviewed, focusing on the impact of age. The
      benefit and risk of a combined pharma-cological and mechanical approach is
      presented. Important differences between a "facilitated PCI" and a "pharmaco
      invasive strategy", particularly in older STEMI patients, are highlighted. It
      will become clear at the end of this review that the knowledge about the benefit
      and risk of reperfusion therapy in the elderly is still incomplete and that more
      clinical trials in the elderly are needed. Practical recommendations for elderly
      patients with STEMI based on the current knowledge have been provided.

PMID- 29633232
TI  - The usefulness of C-reactive protein for the prediction of post-infarct left
      ventricular systolic dysfunction and heart failure.
AB  - Acute myocardial infarction (MI) provokes a systemic inflammatory response that
      may contribute to the development of left ventricular systolic dysfunction (LVSD)
      and heart failure (HF). Patients with post-infarct HF with concomitant LVSD have
      the most unfavourable long-term prognosis. Measurement of C-reactive protein
      (CRP) concentration reflecting an involvement of inflammatory pathways in post
      infarct myocardial damage offers an attractive strategy to improve risk
      stratification and clinical decision-making for early management of high-risk
      patients. Despite growing evidence for the prognostic value of CRP both as a
      single factor and as a component of multi-marker approach in MI, CRP measurement
      is not yet incorporated into current guidelines. This may be due to conflicting
      results reported in existing studies related to various limitations in study
      designs, such as retrospective case control design, prior myocardial damage, CRP
      measurement with low-sensitivity assays, non-homogenous populations with acute
      coronary syndromes, different treatment strategies, small sample sizes, and the
      lack of left ventricular ejection fraction assessment and long-term clinical and
      echocardiographic monitoring. As a result, previous studies have not provided
      conclusive evidence of the prognostic value of CRP for post-infarct LVSD or HF.
      Future studies with an adequate design including upstream mediators of
      inflammation as inflammatory markers are needed to identify the best biomarker
      based strategies for identifying high-risk patients. Further clinical trials
      involving anti-inflammatory therapies target-ing different pathways of
      inflammatory activation in MI should test the inflammatory hypothesis of post
      infarct LVSD and HF. Identifying high-risk patients with persistent post-infarct
      inflammatory response may allow incorporation of pathophysiological guidance for
      implementation of personalised treatment approaches.

PMID- 29633233
TI  - Prognostic value of selected risk scales in patients with end-stage heart
      failure.
AB  - BACKGROUND: Due to the increasing number of patients placed on waiting lists for
      orthotopic heart transplantation (OHT), the selection of patients with the
      highest risk of death has become paramount. AIM: This study aimed to evaluate the
      predictive value of the Model for End-stage Liver Disease eXcluding INR (MELD-XI)
      and Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) scales in
      ambulatory patients awaiting OHT and compare them to the Heart Failure Survival
      Score (HFSS). METHODS: The study was a retrospective review of 370 adult
      ambulatory patients with end-stage heart failure, who were added to the OHT
      waiting list at our institution between 2012 and 2016. RESULTS: The median age of
      the patients was 54.0 (46.0-60.0) years, and 324 (87.6%) of them were male. The
      overall one-year mortality was 27.6%. The areas under the curve (AUCs) for the
      MAGGIC and HFSS scales were comparable: 0.771 (95% confidence interval [CI] 0.720
      0.823); sensitivity 77%, specificity 68% vs. 0.781 (95% CI 0.732-0.829);
      sensitivity 90%, specificity 58%, respectively. The AUC for the MELD-XI scale was
      higher than that for the HFSS scale: 0.812 (95% CI 0.769-0.856); sensitivity 91%,
      specificity 63% vs. 0.781 (95% CI 0.732-0.829) sensitivity 90%, specificity 58%,
      respectively. CONCLUSIONS: Our study demonstrated that elevated MELD-XI and
      MAGGIC scores and lowered HFSS scores were associated with an increased risk of
      death during one-year follow-up. The prognostic utility of the MELD-XI scoring
      system was better than that of the HFSS scale, while the MAGGIC scale was
      comparable to the HFSS.

PMID- 29633234
TI  - Lead-related complications after DDD pacemaker implantation.
AB  - BACKGROUND: Pacing leads remain the weakest link in pacemaker systems despite
      advances in manufacturing technology. AIM: The aim of the study was to assess the
      long-term pacing lead performance in an unselected real-life cohort following
      primary DDD pacing system implantation. METHODS: A single-centre retrospective
      analysis of patients who underwent DDD pacing system implantation between October
      1984 and December 2014 and were followed-up until August 2016 was conducted. The
      inclusion criterion was at least one follow-up visit after post-implant
      discharge. The performance of each atrial and ventricular lead implanted was
      evaluated during the follow-up period, and the incidence of, and predictive
      factors for, lead dislodgement and failure were analysed. RESULTS: The data of
      3771 patients and 24,431.8 patient-years of follow-up were analysed. The mean
      follow-up of patients was 77.7 +/- 61.8 months. During the study period, 7887
      transvenous atrial and right ventricular pacing leads were implanted. Lead
      dislodgement occurred in 94 (1.2%) leads (92 [2.4%] patients), perforation in 11
      (0.1%) leads (10 [0.3%] patients), and lead failure in 329 (4.2%) leads (275
      [7.3%] patients). Atrial lead position was a predictive factor for lead
      dislodgement, while age at implantation, polyurethane 80A insulation, subclavian
      vein access, unipolar lead construction, and lead manufacturer were multivariate
      predictors of lead failure. CONCLUSIONS: Leads with polyurethane 80A insulation,
      unipolar construction, and those implanted via subclavian vein puncture exhibited
      the worst long-term performance.

PMID- 29633235
TI  - Affinity propagation: An exemplar-based tool for clustering in psychological
      research.
AB  - Affinity propagation is a message-passing-based clustering procedure that has
      received widespread attention in domains such as biological science, physics, and
      computer science. However, its implementation in psychology and related areas of
      social science is comparatively scant. In this paper, we describe the basic
      principles of affinity propagation, its relationship to other clustering
      problems, and the types of data for which it can be used for cluster analysis.
      More importantly, we identify the strengths and weaknesses of affinity
      propagation as a clustering tool in general and highlight potential opportunities
      for its use in psychological research. Numerical examples are provided to
      illustrate the method.

PMID- 29633236
TI  - Groundwater Modeling with Nonlinear Uncertainty Analyses to Enhance Remediation
      Design Confidence.
AB  - Soil and groundwater contamination are often managed by establishing on-site
      cleanup targets within the context of risk assessment or risk management
      measures. Decision-makers rely on modeling tools to provide insight; however, it
      is recognized that all models are subject to uncertainty. This case study
      compares suggested remediation requirements using a site-specific numerical model
      and a standardized analytical tool to evaluate risk to a downgradient wetland
      receptor posed by on-site chloride impacts. The base case model, calibrated to
      observed non-pumping and pumping conditions, predicts a peak concentration well
      above regulatory criteria. Remediation scenarios are iteratively evaluated to
      determine a remediation design that adheres to practical site constraints, while
      minimizing the potential for risk to the downgradient receptor. A nonlinear
      uncertainty analysis is applied to each remediation scenario to stochastically
      evaluate the risk and find a solution that meets the site-owner risk tolerance,
      which in this case required a risk-averse solution. This approach, which couples
      nonlinear uncertainty analysis with a site-specific numerical model provides an
      enhanced level of knowledge to foster informed decision-making (i.e., risk-of
      success) and also increases stakeholder confidence in the remediation design.

PMID- 29633237
TI  - Use of Intensive Glycemic Management in Older Adults with Diabetes Mellitus.
AB  - OBJECTIVES: To examine the proportion of older adults with diabetes mellitus
      treated with tight glucose control and the factors associated with this practice.
      DESIGN: Cross-sectional analysis. SETTING: Outpatient sites in the Diabetes
      Collaborative Registry (N=151). PARTICIPANTS: Adults aged 75 and older with type
      2 diabetes mellitus (N=42,669). MEASUREMENTS: Participants were categorized based
      on glycosylated hemoglobin (HbA1c) and glucose-lowering medications: poor control
      (HbA1c >9%), moderate control (HbA1c 8-9%), conservative control (HbA1c 7-8%),
      tight control (HbA1c <7%) with low-risk agents (low risk for hypoglycemia), tight
      control with high-risk agents, and diet control (HbA1c <7% taking no glucose
      lowering medications). We used hierarchical logistic regression to examine
      participant and site factors associated with tight control and high-risk agents
      versus conservative or tight control and low-risk agents. RESULTS: Of 30,696
      participants without diet-controlled diabetes, 5,596 (18%) had moderate or poor
      control, 9,227 (30%) had conservative control, 7,893 (26%) had tight control
      taking low-risk agents, and 7,980 (26%) had tight control taking high-risk
      agents. Older age, male sex, heart failure, chronic kidney disease, and coronary
      artery disease were each independently associated with greater odds of tight
      control with high-risk agents. There were no differences according to practice
      specialty (endocrinology, primary care, cardiology) in how aggressively
      participants were managed. CONCLUSION: One-quarter of U.S. older adults with type
      2 diabetes mellitus are tightly controlled with glucose-lowering medications that
      have a high risk of hypoglycemia. These results suggest potential overtreatment
      of a substantial proportion of people and should encourage further efforts to
      translate guidelines to daily practice.

PMID- 29633238
TI  - Drinking Ethanol Has Few Acute Effects on CYP2C9, CYP2C19, NAT2, and P
      Glycoprotein Activities but Somewhat Inhibits CYP1A2, CYP2D6, and Intestinal
      CYP3A: So What?
AB  - We quantified the effect of acute ethanol exposure (initial blood concentrations
      0.7 g/L) on major drug metabolizing enzymes and p-glycoprotein. Sixteen healthy
      Caucasians participated in a randomized crossover study with repeated
      administration of either vodka or water. Enzyme/transporter activity was assessed
      by a cocktail of probe substrates, including caffeine (CYP1A2/NAT2), tolbutamide
      (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), midazolam (CYP3A), and
      digoxin (P-glycoprotein). The ratio of AUC0-t of dextromethorphan for
      ethanol/water coadministration was 1.95 (90% confidence interval (CI) 1.48-2.58).
      The effect was strongest in individuals with a CYP2D6 genotype predicting high
      activity (n = 7, ratio 2.66, 90% CI 1.65-4.27). Ethanol increased caffeine AUC0-t
      1.38-fold (90% CI 1.25-1.52) and reduced intestinal midazolam extraction 0.77
      fold (90% CI 0.69-0.86). The other probe drugs were not affected by ethanol. The
      results suggest that acute ethanol intake typically has no clinically important
      effect on the enzymes/transporters tested.

PMID- 29633239
TI  - Postictal suppression and seizure durations: A patient-specific, long-term iEEG
      analysis.
AB  - OBJECTIVE: We report on patient-specific durations of postictal periods in long
      term intracranial electroencephalography (iEEG) recordings. The objective was to
      investigate the relationship between seizure duration and postictal suppression
      duration. METHODS: Long-term recording iEEG from 9 patients (>50 seizures
      recorded) were analyzed. In total, 2310 seizures were recorded during a total of
      13.8 years of recording. Postictal suppression duration was calculated as the
      duration after seizure termination until total signal energy returned to
      background levels. The relationship between seizure duration and postictal
      suppression duration was quantified using the correlation coefficient (r). The
      effects of populations of seizures within patients, on correlations, were also
      considered. Populations of seizures within patients were distinguished by seizure
      duration thresholds and k-means clustering along the dimensions of seizure
      duration and postictal suppression duration. The effects of bursts of seizures
      were also considered by defining populations based on interseizure interval
      (ISI). RESULTS: Seizure duration accounted for 40% of postictal suppression
      duration variance, aggregated across all patients and seizures. Seizure duration
      accounted for more than 25% of the variance in postictal suppression duration in
      2 patients and accounted for less than 25% in the remaining 7. In 3 patients,
      heat maps showed multiple distinct postictal patterns indicating multiple
      populations of seizures. When accounting for these populations, seizure duration
      accounted for less than 25% of the variance in postictal duration in all
      populations. Variance in postictal suppression duration accounted for less than
      10% of ISI variance in all patients. SIGNIFICANCE: We have previously
      demonstrated that some patients have multiple seizure populations distinguishable
      by seizure duration. This article shows that different seizure populations have
      distinct and consistent postictal behaviors. The existence of multiple
      populations in some patients has implications for seizure management and
      forecasting, whereas the distinct postictal behaviors may have implications for
      sudden unexpected death in epilepsy (SUDEP) prediction and prevention.

PMID- 29633240
TI  - Transient improvement of skin symptoms in an adult patient with pediatric-onset
      cutaneous mastocytosis treated with interferon-alpha.

PMID- 29633241
TI  - Intravenous lacosamide for treatment of absence status epilepticus in genetic
      generalized epilepsy: A case report and review of literature.
AB  - BACKGROUND: Nearly 10 years after its introduction into the market, the
      significance of lacosamide in genetic generalized epilepsies is still unclear.
      Its new mode of action may qualify lacosamide as a therapeutic agent in this
      entity, but only a limited number of cases have been published so far. AIM: To
      describe the efficacy of lacosamide as treatment in a patient with the absence
      status epilepticus. METHOD: We report on a 28-year-old woman with genetic
      generalized epilepsy who suffered recurrent absence status epilepticus during
      video-EEG-monitoring. After treatment failure of first- and second-line
      medication, lacosamide was administered. The outcome in this patient was
      evaluated, and a systematic literature review was performed for the use of
      lacosamide in the absence status epilepticus. RESULTS: After application of 400
      mg lacosamide intravenously, the absence status epilepticus terminated within 30
      minutes. No further seizures or epileptiform discharges reoccurred until the end
      of video-EEG-Monitoring 3 days later. CONCLUSIONS: The role of lacosamide as a
      therapeutic option in patients with the absence status epilepticus is unclear.
      Only two cases have been reported so far with conflicting results. Further
      randomized controlled studies are required to validate the relevance of
      lacosamide as treatment for status epilepticus in genetic generalized and the
      absence epilepsy.

PMID- 29633242
TI  - Alan C. Walker (1938-2017).

PMID- 29633243
TI  - Internet gaming disorder in children and adolescents: a systematic review.
AB  - AIM: Internet gaming disorder (IGD) is a serious disorder leading to and
      maintaining pertinent personal and social impairment. IGD has to be considered in
      view of heterogeneous and incomplete concepts. We therefore reviewed the
      scientific literature on IGD to provide an overview focusing on definitions,
      symptoms, prevalence, and aetiology. METHOD: We systematically reviewed the
      databases ERIC, PsyARTICLES, PsycINFO, PSYNDEX, and PubMed for the period January
      1991 to August 2016, and additionally identified secondary references. RESULTS:
      The proposed definition in the Diagnostic and Statistical Manual of Mental
      Disorders, Fifth Edition provides a good starting point for diagnosing IGD but
      entails some disadvantages. Developing IGD requires several interacting internal
      factors such as deficient self, mood and reward regulation, problems of decision
      making, and external factors such as deficient family background and social
      skills. In addition, specific game-related factors may promote IGD. Summarizing
      aetiological knowledge, we suggest an integrated model of IGD elucidating the
      interplay of internal and external factors. INTERPRETATION: So far, the concept
      of IGD and the pathways leading to it are not entirely clear. In particular, long
      term follow-up studies are missing. IGD should be understood as an endangering
      disorder with a complex psychosocial background. WHAT THIS PAPER ADDS: In
      representative samples of children and adolescents, on average, 2% are affected
      by Internet gaming disorder (IGD). The mean prevalences (overall, clinical
      samples included) reach 5.5%. Definitions are heterogeneous and the relationship
      with substance-related addictions is inconsistent. Many aetiological factors are
      related to the development and maintenance of IGD. This review presents an
      integrated model of IGD, delineating the interplay of these factors.

PMID- 29633244
TI  - Motor development in infancy is related to cognitive function at 4 years of age.
AB  - AIM: Evidence is accumulating that motor and cognitive development are
      interrelated. This study investigates associations between motor development in
      infancy and cognitive function at 4 years of age. METHOD: This study is part of
      the Groningen prospective cohort study on the development of children born after
      assisted reproductive techniques such as in vitro fertilization. The study group
      consisted of 223 children (119 males, 104 females) born to subfertile couples
      (median gestational age 39.6wks, range 30-43wks). Motor behaviour was assessed
      with the Infant Motor Profile (IMP) at 4 months, 10 months, and 18 months. IQ was
      evaluated at 4 years with the Kaufman Assessment Battery for Children, Second
      Edition. Latent class growth modelling was used to analyse relations between IMP
      and IQ scores. RESULTS: Infants with low total IMP scores had an IQ that was 8.9
      points lower at 4 years than infants with typical IMP scores (95% confidence
      interval 3.6-14.1). Also, low scores in the domains of variation and performance
      were associated with a lower IQ at 4 years of age, by 6.1 points and 13.2 points
      respectively. INTERPRETATION: Motor development in relatively low-risk infants is
      associated with cognition at 4 years of age. In particular, low motor variation
      and performance are associated with a lower IQ at 4 years of age. WHAT THIS PAPER
      ADDS: Motor development in infancy is directly related to cognitive function at 4
      years of age. This relationship is most pronounced for infant motor variation and
      performance. The size of the differences in IQ is clinically relevant.

PMID- 29633245
TI  - TASP1 is deleted in an infant with developmental delay, microcephaly, distinctive
      facial features, and multiple congenital anomalies.
AB  - We report a 20p12.1 homozygous deletion including exons 5-10 of the TASP1 gene in
      an infant with developmental delay, acquired microcephaly, distinctive facial
      features, and multiple congenital anomalies involving skeletal, cardiac, and
      renal systems. TASP1 encodes taspase 1 which is responsible for cleaving, thus
      activating, a number of transcription factors including the mixed lineage
      leukemia 1 (MLL1). Taspase 1-deficient mice showed early lethality, skeletal
      abnormalities, and growth failure, which support a potentially causal role of
      TASP1 deletion in this infant. Furthermore, the infant reported here had many of
      the features seen in Wiedemann-Steiner syndrome which is caused by MLL1 defects.
      Such observation further supports that TASP1 is a novel disease-related gene that
      is associated with a disease phenotype overlapping with Wiedemann-Steiner
      syndrome as both are caused by defects in the same pathway.

PMID- 29633247
TI  - Ambient benzene at the residence and risk for subtypes of childhood leukemia,
      lymphoma and CNS tumor.
AB  - Exposure to benzene increases the risk for acute myeloid leukemia and possibly
      other types of cancer in adults. For children, only limited evidence about
      benzene and cancer exists. A few studies have indicated that benzene may increase
      risk for some subtypes of childhood cancer but not for others. We aimed to
      investigate if outdoor levels of benzene at the residence increase the risk for
      subtypes of leukemia, lymphoma and CNS tumor in children. We identified 1,989
      children diagnosed with leukemia, lymphoma or CNS tumor during 1968-1991 in the
      Danish Cancer Registry and randomly selected 5,506 control children from the
      Danish population, matched on sex, age and calendar time. We traced residential
      history of all children from 9 months before birth to time of diagnosis,
      calculated outdoor benzene concentration at all addresses and summarized
      cumulative exposure over fetal and childhood periods separately. We used
      conditional logistic regression for the statistical analyses. Benzene exposure
      during childhood above the 90th percentile was associated with relative risks for
      acute lymphocytic leukemia (ALL) and acute myeloid leukemia (AML) of 1.0 (95%
      confidence intervals (CI): 0.6-1.7) and 1.9 (95% CI: 0.3-11.1), respectively,
      when compared with exposure levels below the median. For CNS tumors, there was a
      tendency of lower risk for ependymoma and higher risk for medulloblastoma in
      association with higher exposure. In conclusion, benzene was associated with
      higher risk for childhood AML, but not ALL, which is consistent with the few
      previous studies.

PMID- 29633248
TI  - Ictal connectivity in childhood absence epilepsy: Associations with outcome.
AB  - OBJECTIVE: The understanding of childhood absence epilepsy (CAE) has been
      revolutionized over the past decade, but the biological mechanisms responsible
      for variable treatment outcomes are unknown. Our purpose in this prospective
      observational study was to determine how pretreatment ictal network pathways,
      defined using a combined electroencephalography (EEG)-functional magnetic
      resonance imaging (EEG-fMRI) and magnetoencephalography (MEG) effective
      connectivity analysis, were related to treatment response. METHODS: Sixteen
      children with newly diagnosed and drug-naive CAE had 31 typical absence seizures
      during EEG-fMRI and 74 during MEG. The spatial extent of the pretreatment ictal
      network was defined using fMRI hemodynamic response with an event-related
      independent component analysis (eICA). This spatially defined pretreatment ictal
      network supplied prior information for MEG-effective connectivity analysis
      calculated using phase slope index (PSI). Treatment outcome was assessed 2 years
      following diagnosis and dichotomized to ethosuximide (ETX)-treatment responders
      (N = 11) or nonresponders (N = 5). Effective connectivity of the pretreatment
      ictal network was compared to the treatment response. RESULTS: Patterns of
      pretreatment connectivity demonstrated strongest connections in the thalamus and
      posterior brain regions (parietal, posterior cingulate, angular gyrus, precuneus,
      and occipital) at delta frequencies and the frontal cortices at gamma frequencies
      (P < .05). ETX treatment nonresponders had pretreatment connectivity, which was
      decreased in the precuneus region and increased in the frontal cortex compared to
      ETX responders (P < .05). SIGNIFICANCE: Pretreatment ictal connectivity
      differences in children with CAE were associated with response to antiepileptic
      treatment. This is a possible mechanism for the variable treatment response seen
      in patients sharing the same epilepsy syndrome.

PMID- 29633246
TI  - The physiological linkage between molar inclination and dental macrowear pattern.
AB  - OBJECTIVES: Exact symmetry and perfect balance between opposite jaw halves, as
      well as between antagonistic teeth, is not frequently observed in natural
      masticatory systems. Research results show that asymmetry in our body, skull, and
      jaws is often related to genetic, epigenetic, environmental and individual
      ontogenetic factors. Our study aims to provide evidence for a significant link
      between masticatory asymmetry and occlusal contact between antagonist teeth by
      testing the hypothesis that tooth inclination is one of the mechanisms driving
      distribution of wear in masticatory phases in addition to dietary and cultural
      habits. MATERIALS AND METHODS: The present work investigates the relationship
      between dental macrowear patterns and tooth inclinations on a sample of complete
      maxillary and mandibular 3D models of dental arches from 19 young and adult
      Yuendumu Aboriginal individuals. The analysis was carried out on first molars
      (M1) from all quadrants. Occlusal Fingerprint Analysis was used for the
      quantification of macrowear patterns, and 2D cross-sectional geometric analysis
      was carried out to investigate asymmetry in dental arches. RESULTS: The asymmetry
      is highly variable on both arches, and it is associated with differences in the
      inclination of upper M1 crowns. Each molar has variable inclination
      (buccal/lingual) which influence tooth to tooth contact, producing greater or
      lesser variation in wear pattern. Interindividual variability of morphological
      variation of the occlusal relationship has to be considered in macrowear
      analysis. DISCUSSION: Our results suggest that overall asymmetry in the
      masticatory apparatus in modern humans affects occlusal contact areas between
      antagonist teeth influencing macrowear and chewing efficiency during ontogeny.

PMID- 29633249
TI  - As you like it: How the same data can support manifold views of overdiagnosis in
      breast cancer screening.
AB  - Overdiagnosis estimates have varied substantially, causing confusion. The
      discussions have been complicated by the fact that population and study design
      have varied substantially between studies. To help assess the impact of study
      design choices on the estimates, we compared them on a single population. A
      cohort study from Funen County, Denmark, recently suggested little (~1%)
      overdiagnosis. It followed previously screened women for up to 14 years after
      screening had ended. Using publically available data from Funen, we recreated the
      designs from five high-estimate, highly cited studies from various countries.
      Selected studies estimated overdiagnosis to be 25-54%. Their designs were adapted
      only to the extent that they reflect the start of screening in Funen in 1993. The
      reanalysis of the Funen data resulted in overdiagnosis estimates that were
      remarkably similar to those from the original high-estimate age-period studies,
      21-55%. In additional analyses, undertaken to elucidate the effect of the
      individual components of the study designs, overdiagnosis estimates were more
      than halved after the most likely changes in the background risk were accounted
      for and decreased additionally when never-screened birth cohorts were excluded
      from the analysis. The same data give both low and high estimates of
      overdiagnosis, it all depends on the study design. This stresses the need for a
      careful scrutiny of the validity of the assumptions underpinning the estimates.
      Age-period analyses of breast cancer overdiagnosis suggesting very high
      frequencies of overdiagnosis rested on unmet assumptions. This study showed that
      overdiagnosis estimates should in the future be requested to adequately control
      for the background risk and include an informative selection of the studied
      population to achieve valid and comparable estimates of overdiagnosis.

PMID- 29633250
TI  - Committee Representation and Medicare Reimbursements-An Examination of the
      Resource-Based Relative Value Scale.
AB  - BACKGROUND: The Resource-Based Relative Value Scale Update Committee (RUC)
      submits recommended reimbursement values for physician work (wRVUs) under
      Medicare Part B. The RUC includes rotating representatives from medical
      specialties. OBJECTIVE: To identify changes in physician reimbursements
      associated with RUC rotating seat representation. DATA SOURCES: Relative Value
      Scale Update Committee members 1994-2013; Medicare Part B Relative Value Scale
      1994-2013; Physician/Supplier Procedure Summary Master File 2007; Part B National
      Summary Data File 2000-2011. STUDY DESIGN: I match service and procedure codes to
      specialties using 2007 Medicare billing data. Subsequently, I model wRVUs as a
      function of RUC rotating committee representation and level of code
      specialization. PRINCIPAL FINDINGS: An annual RUC rotating seat membership is
      associated with a statistically significant 3-5 percent increase in Medicare
      expenditures for codes billed to that specialty. For codes that are performed by
      a small number of physicians, the association between reimbursement and rotating
      subspecialty representation is positive, 0.177 (SE = 0.024). For codes that are
      performed by a large number of physicians, the association is negative, -0.183
      (SE = 0.026). CONCLUSIONS: Rotating representation on the RUC is correlated with
      overall reimbursement rates. The resulting differential changes may exacerbate
      existing reimbursement discrepancies between generalist and specialist
      practitioners.

PMID- 29633251
TI  - Operating room-to-incision interval and neonatal outcome in emergency caesarean
      section: a retrospective 5-year cohort study.
AB  - We conducted a 5-year retrospective cohort study on women undergoing caesarean
      section to investigate factors influencing the operating room-to-incision
      interval. Time-to-event analysis was performed for category-1 caesarean section
      using a Cox proportional hazards regression model. Covariates included:
      anaesthetic technique; body mass index; age; parity; time of delivery; and
      gestational age. Binary logistic regression was performed for 5-min Apgar score
      >= 7. There were 677 women who underwent category-1 caesarean section and who met
      the entry criteria. Unadjusted median (IQR [range]) operating room-to-incision
      intervals were: epidural top-up 11 (7-17 [0-87]) min; general anaesthesia 6 (4-11
      [0-69]) min; spinal 13 (10-20 [0-83]) min; and combined spinal-epidural 24 (13-35
      [0-75]) min. Cox regression showed general anaesthesia to be the most rapid
      method with a hazard ratio (95%CI) of 1.97 (1.60-2.44; p < 0.0001), followed by
      epidural top-up (reference group), spinal anaesthesia 0.79 (0.65-0.96; p = 0.02)
      and combined spinal-epidural 0.48 (0.35-0.67; p < 0.0001). Underweight and
      overweight body mass indexes were associated with longer operating room-to
      incision intervals. General anaesthesia was associated with fewer 5-min Apgar
      scores >= 7 with an odds ratio (95%CI) of 0.28 (0.11-0.68; p < 0.01). There was
      no difference in neonatal outcomes between the first and fifth quintiles for
      operating room-to-incision intervals. General anaesthesia is associated with the
      most rapid operating room-to-incision interval for category-1 caesarean section,
      but is also associated with worse short term neonatal outcomes. Longer operating
      room-to-incision intervals were not associated with worse neonatal outcomes.

PMID- 29633252
TI  - A patient-centered team approach in oncology.

PMID- 29633253
TI  - Identification of novel cyclin gene fusion transcripts in endometrioid ovarian
      carcinomas.
AB  - Formation of fusion genes is pathogenetically crucial in many solid tumors. They
      are particularly characteristic of several mesenchymal tumors, but may also be
      found in epithelial neoplasms. Ovarian carcinomas, too, may harbor fusion genes
      but only few of these were found to be recurrent with a rate ranging from 0.5 to
      5%. Because most attempts to find specific and recurrent fusion transcripts in
      ovarian carcinomas focused exclusively on high-grade serous carcinomas, the
      situation in the other carcinoma subgroups remains largely uninvestigated as far
      as fusion genes are concerned. We performed transcriptome sequencing on a series
      of 34 samples from ovarian tumors that included borderline, clear cell, mucinous,
      endometrioid, low-grade and high-grade serous carcinomas in search of fusion
      genes typical of these subtypes. We found a total of 24 novel fusion transcripts.
      The PCMTDI-CCNL2 fusion transcript, which involves a member of the cyclin family,
      was found recurrently involved but only in endometrioid carcinomas (4 of 18
      tumors; 22%). We also found three additional fusion transcripts involving genes
      belonging to the cyclin family: ANXA5-CCNA2 and PDE4D-CCNB1 were detected in two
      endometrioid carcinomas, whereas CCNY-NRG4 was identified in a clear cell
      carcinoma. The recurrent involvement of CCNL2 in four fusions and of three other
      genes of the cyclin family in three additional transcripts hints that
      deregulation of cyclin genes is important in the pathogenesis of ovarian
      carcinomas in general but of endometrioid carcinomas particularly.

PMID- 29633254
TI  - Teaching & Learning Tips 7: small-group discussion.
AB  - Challenge: The success of a small-group discussion depends in large part on the
      effectiveness of the facilitator or small-group tutor. How can a facilitator
      successfully manage diverse views and knowledge bases of participants while also
      contributing as a member of the group? Herein, we provide tips for managing small
      group discussions that can be applied widely in dermatology didactics.

PMID- 29633256
TI  - A one-step method for modelling longitudinal data with differential equations.
AB  - Differential equation models are frequently used to describe non-linear
      trajectories of longitudinal data. This study proposes a new approach to estimate
      the parameters in differential equation models. Instead of estimating derivatives
      from the observed data first and then fitting a differential equation to the
      derivatives, our new approach directly fits the analytic solution of a
      differential equation to the observed data, and therefore simplifies the
      procedure and avoids bias from derivative estimations. A simulation study
      indicates that the analytic solutions of differential equations (ASDE) approach
      obtains unbiased estimates of parameters and their standard errors. Compared with
      other approaches that estimate derivatives first, ASDE has smaller standard
      error, larger statistical power and accurate Type I error. Although ASDE obtains
      biased estimation when the system has sudden phase change, the bias is not
      serious and a solution is also provided to solve the phase problem. The ASDE
      method is illustrated and applied to a two-week study on consumers' shopping
      behaviour after a sale promotion, and to a set of public data tracking
      participants' grammatical facial expression in sign language. R codes for ASDE,
      recommendations for sample size and starting values are provided. Limitations and
      several possible expansions of ASDE are also discussed.

PMID- 29633255
TI  - HDAC5-LSD1 axis regulates antineoplastic effect of natural HDAC inhibitor
      sulforaphane in human breast cancer cells.
AB  - Our recent studies have shown that cross-talk between histone deacetylase 5
      (HDAC5) and lysine-specific demethylase 1 (LSD1) facilitates breast cancer
      progression. In this work, we demonstrated that regulatory activity at -356 to 
      100 bp promoter element plays a critical role in governing HDAC5 transcription.
      By using DNA affinity precipitation and mass spectrometry, we identified a group
      of factors that bind to this element. Among these factors, Upstream Transcription
      Factor 1 (USF1) was shown to play a critical role in controlling HDAC5
      transcription. Through screening a panel of epigenetic modifying drugs, we showed
      that a natural bioactive HDAC inhibitor, sulforaphane, downregulated HDAC5
      transcription by blocking USF1 activity. Sulforaphane facilitated LSD1
      ubiquitination and degradation in an HDAC5-dependent manner. A comparative
      microarray analysis demonstrated a genome wide cooperative effect of HDAC5 and
      LSD1 on cancer-related gene expression. shRNA knockdown and sulforaphane
      inhibition of HDAC5/LSD1 exhibited similar effects on expression of HDAC5/LSD1
      target genes. We also showed that coordinated cross-talk of HDAC5 and LSD1 is
      essential for the antitumor efficacy of sulforaphane. Combination treatment with
      sulforaphane and a potent LSD1 inhibitor resulted in synergistic growth
      inhibition in breast cancer cells, but not in normal breast epithelial cells.
      Furthermore, combined therapy with sulforaphane and LSD1 inhibitor exhibited
      superior inhibitory effect on MDA-MB-231 xenograft tumor growth. Taken together,
      our work demonstrates that HDAC5-LSD1 axis is an effective drug target for breast
      cancer. Inhibition of HDAC5-LSD1 axis with sulforaphane blocks breast cancer
      growth and combined treatment with LSD1 inhibitor improves the therapeutic
      efficacy of sulforaphane.

PMID- 29633257
TI  - Physiologically Based Pharmacokinetic Modeling in Pregnancy: A Systematic Review
      of Published Models.
AB  - During recent years there has been a surge in developing and applying
      physiologically based pharmacokinetic (PBPK) models in pregnant women to better
      understand and predict changes in drug pharmacokinetics throughout pregnancy. As
      a consequence, the number of publications focusing on pregnancy PBPK models has
      increased substantially. However, to date these models, especially across various
      platforms, have not been systematically evaluated. Hence, this review aims to
      assess published PBPK models in pregnancy used for therapeutic purposes.

PMID- 29633258
TI  - A comparative study on pathological features of transgenic rat lines expressing
      either three or four repeat misfolded tau.
AB  - Human tauopathies represent a heterogeneous group of neurodegenerative disorders
      characterized by distinct clinical features, typical histopathological
      structures, and defined ratio(s) of three-repeat and four-repeat tau isoforms
      within pathological aggregates. How the optional microtubule-binding repeat of
      tau influences this differentiation of pathologies is understudied. We have
      previously generated and characterized transgenic rodent models expressing human
      truncated tau aa151-391 with either three (SHR24) or four microtubule-binding
      repeats (SHR72). Here, we compare the behavioral and neuropathological hallmarks
      of these two transgenic lines using a battery of tests for sensorimotor,
      cognitive, and neurological functions over the age range of 3.5-15 months.
      Progression of sensorimotor and neurological deficits was similar in both
      transgenic lines; however, the lifespan of transgenic line SHR72 expressing
      truncated four-repeat tau was markedly shorter than SHR24. Moreover, the
      expression of three or four-repeat tau induced distinct neurofibrillary pathology
      in these lines. Transgenic lines displayed different distribution of tau
      pathology and different type of neurofibrillary tangles. Our results suggest that
      three- and four-repeat isoforms of tau may display different modes of action in
      the diseased brain.

PMID- 29633259
TI  - Antimutagenic constituents from Monanthotaxis caffra (Sond.) Verdc.
AB  - OBJECTIVES: Monanthotaxis caffra (Sond.) Verdc. (Annonaceae) has been reported to
      possess antitumoural properties. Preliminary screening showed that the crude
      methanolic leaf extract had strong antimutagenic effects against aflatoxin B1 
      induced mutagenicity. The aim of this study was to isolate and evaluate the
      antimutagenic properties of the active constituents from M. caffra. METHODS:
      Different chromatographic, spectroscopic and spectrometric techniques were used
      for the isolation and identification of the antimutagenic constituents. The
      antimutagenic effect of the extract and compounds was evaluated using Ames,
      Vitotox and Comet assays. KEY FINDINGS: Bioassay-guided fractionation of the
      methanolic leaf extract yielded two antimutagenic compounds identified as (+)
      crotepoxide and 5,6-diacetoxy1-benzoyloxymethyl-1,3-cyclohexadiene. Crotepoxide
      had strong antimutagenicity in the Vitotox assay with an IC50 value of 131
      MUg/ml. 5,6-Diacetoxy-1-benzoyloxymethyl-1,3-cyclohexadiene showed strong
      antimutagenic activity in the Ames assay with an IC50 value of 348.9 MUg/plate
      and no antimutagenic activity in the Vitotox test. Furthermore, the compound was
      able to inhibit, block or prevent biotransformation of aflatoxin B1 by repressing
      the proteins involved in transcription. CONCLUSIONS: Crotepoxide and 5,6
      diacetoxy-1-benzoyloxymethyl-1,3-cyclohexadiene have the potential to mitigate
      the risks arising from consumption of aflatoxin B1 -contaminated food and feed.

PMID- 29633260
TI  - Animalizing the disadvantaged, mechanizing the wealthy: The convergence of socio
      economic status and attribution of humanity.
AB  - Differences between groups in socio-economic status (SES) are becoming more
      salient nowadays. In this context, we examined the animalistic and mechanistic
      dehumanization that both low and high-SES groups may experience respectively by
      conducting three studies. In study 1, we manipulated the SES of two fictitious
      groups (low vs. high-SES) and measured the humanity ascribed to them. Results
      showed that the low-SES group was animalized in comparison with the high-SES
      group, which was mechanized. In study 2, we manipulated the humanity of two
      fictitious groups by describing them as animals or machines and measured the
      perceived SES of the groups. Participants tended to attribute lower SES to the
      group described as animals and higher SES to the group described as machines.
      Finally, in study 3, we used an Implicit Association Test to replicate the
      results of studies 1 and 2. Taken together, these studies show that low-SES
      groups are considered as animal-like whereas high-SES groups are seen as robot
      like. We discuss the implications of these findings in relation to the
      justification of income inequality within our society.

PMID- 29633261
TI  - Brain natriuretic peptide serum levels in periodontitis.
AB  - BACKGROUND AND OBJECTIVE: N-terminal-pro-brain natriuretic peptide (NT-proBNP) is
      expressed during inflammation and considered to be a biomarker of cardiovascular
      disease (CVD). In the last decade, evidence has suggested that periodontitis is
      associated with CVD. However, little is known of the potential role of this
      peptide in periodontal disease. The aims of this study were to examine whether
      the levels of NT-proBNP in serum are increased in periodontal disease and if
      there is a relationship to severity of periodontitis. MATERIAL AND METHODS: A
      case-control study was carried out, in which serum samples were collected from 40
      patients with periodontitis and from 40 nonperiodontitis individuals. Full
      periodontal examination was performed in all subjects. Demographic information,
      and clinical and history of certain diseases were also recorded. Determinations
      of serum NT-proBNP and high-sensitivity C-reactive protein concentrations were
      carried out in an independent laboratory. RESULTS: The levels of NT-proBNP in
      serum were significantly higher in patients with periodontitis compared with
      controls (87.9 pg/mL vs 29.9 pg/mL, P < .0001). In addition, as periodontal
      disease progressed, the levels of NT-proBNP increased. Multivariable regression
      analysis showed that the periodontal inflamed surface area, a measure of
      periodontal inflammation and disease activity, was the only periodontal parameter
      significantly associated with elevated concentrations of NT-proBNP in serum (R2 
      = .777, P < .0001). CONCLUSION: In periodontitis, increased serum NT-proBNP
      levels are observed in comparison with individuals without periodontitis.
      Moreover, the greater the degree of periodontal destruction, the higher the
      levels of NT-proBNP in serum.

PMID- 29633262
TI  - Comparative analysis of early adverse events of pelvic organ prolapse repair with
      or without transvaginal mesh using Clavien-Dindo classification.
AB  - OBJECTIVE: To assess adverse events following surgical repair of pelvic organ
      prolapse (POP) with or without the use of transvaginal mesh. METHODS: The present
      retrospective study was conducted among women who underwent surgical POP repair
      at Soroka University Medical Center, Beer Sheva, Israel, between January 1, 2013,
      and December 31, 2015. Patients underwent anterior and posterior colporrhaphy
      either with transvaginal mesh (Elevate Prolapse Repair System; American Medical
      Systems, Minnetonka, MN, USA) or without transvaginal mesh (native tissue
      repair). Perioperative adverse events were assessed using the Clavien-Dindo
      classification; multivariate regression models were constructed to predict minor
      and major adverse events. RESULTS: There were 111 women included; 35 were treated
      with transvaginal mesh, and 76 underwent native tissue repair. Women undergoing
      native tissue repair had a lower mean grade of cystocele (P=0.023) and a higher
      rate of urinary stress incontinence (P=0.017) than patients treated with
      transvaginal mesh. The duration of surgery (P=0.002), duration of hospitalization
      (P<0.001), and the amount of blood loss (P=0.021) were lower in the native tissue
      repair group. Repair with transvaginal mesh was not associated with increased
      odds of major or minor adverse events (P>0.05 for all models examined).
      CONCLUSION: Perioperative and postoperative adverse events were comparable
      regardless of the operative approach.

PMID- 29633263
TI  - The importance of body satisfaction to physical self-concept and body mass index
      in Spanish adolescents.
AB  - This research examines the association between measured body mass index (BMI) and
      the perception of BMI by young students. Moreover, this research tests the
      importance of BMI and self-concept, in order to predict body dissatisfaction in
      high school students. The sample consisted of 2087 individuals from different
      high schools in Extremadura, Spain, both males (n = 1046) and females (n = 1041),
      ranging in age from 15 to 17 years old (M = 15.42; SD = 0.86). Initially,
      participants' BMIs were assessed through anthropometry. Later, all individuals
      were asked about their weight and height, and their self-reported BMI was
      calculated. Participants also answered a questionnaire about their perception of
      self-concept, as well as completed a test about body image perception using
      Stunkard images. Outcomes revealed that factors concerning self-concept and
      perceived BMI explained body dissatisfaction. Finally, results are discussed with
      the aim of improving knowledge in body dissatisfaction context.

PMID- 29633265
TI  - FoxP3+ regulatory T cells, interleukin 17 and mast cells in chronic inflammatory
      periodontal disease.
AB  - BACKGROUND AND OBJECTIVE: T cells are known to play a pivotal role in periodontal
      disease; however, less is known about the T-helper subsets of regulatory T cells
      (Tregs) and Th17 cells. The aim of this study was to investigate the cell types
      expressing FoxP3 and interleukin (IL)-17A within periodontal disease tissues and
      to determine gene and protein expression profiles associated with periodontitis.
      MATERIAL AND METHODS: A total of 10 healthy/gingivitis and 10 chronic
      periodontitis tissues were investigated. Immunohistochemistry and
      immunofluorescence techniques were used to identify the FoxP3 and IL17-positive
      cells and to determine the cell types respectively. Gene expression was
      determined using semi-quantitative polymerase chain reaction array technology
      that allowed the analysis of 84 pathway-focused genes known to be associated with
      Tregs and Th17 cells. Transforming growth factor (TGF)-beta1, IL10 and IL17A
      protein levels were determined using enzyme-linked immunosorbent assay. RESULTS:
      Double immunofluorescence labeling revealed that all FoxP3+ cells were CD4+ ,
      while IL17+ cells were neither CD4+ nor CD8+ but were tryptase+ , suggestive of
      mast cells. More FoxP3+ cells than IL17+ cells were found in all the tissues
      examined and overall there were few IL17+ cells. Statistically significant
      increases in gene expression were found for STAT5A, STAT3, SOCS1, TGFbeta1 and
      IL10 in the chronic periodontitis specimens predominantly infiltrated with B
      cells and plasma cells when compared with healthy/gingivitis specimens
      predominantly infiltrated with T cells. Protein analysis demonstrated higher
      levels of the TGFbeta1 and IL10 cytokines in periodontitis tissues and in B-cell
      and plasma cell predominant gingival tissues than in healthy/gingivitis tissues
      and T-cell predominant gingival tissues. IL17A gene and protein expression was
      not detected in any of the tissues. CONCLUSION: Based on the findings of this
      study, we suggest that the source of low levels of IL17A in periodontal tissues
      is mast cells not Th17 cells and that Tregs may have a more prominent role in the
      pathogenesis of periodontal disease than Th17 cells.

PMID- 29633264
TI  - GABA-like immunoreactivity in Biomphalaria: Colocalization with tyrosine
      hydroxylase-like immunoreactivity in the feeding motor systems of panpulmonate
      snails.
AB  - The simpler nervous systems of certain invertebrates provide opportunities to
      examine colocalized classical neurotransmitters in the context of identified
      neurons and well defined neural circuits. This study examined the distribution of
      gamma-aminobutyric acid-like immunoreactivity (GABAli) in the nervous system of
      the panpulmonates Biomphalaria glabrata and Biomphalaria alexandrina, major
      intermediate hosts for intestinal schistosomiasis. GABAli neurons were localized
      in the cerebral, pedal, and buccal ganglia of each species. With the exception of
      a projection to the base of the tentacle, GABAli fibers were confined to the CNS.
      As GABAli was previously reported to be colocalized with markers for dopamine
      (DA) in five neurons in the feeding network of the euopisthobranch gastropod
      Aplysia californica (Diaz-Rios, Oyola, & Miller, 2002), double-labeling protocols
      were used to compare the distribution of GABAli with tyrosine hydroxylase
      immunoreactivity (THli). As in Aplysia, GABAli-THli colocalization was limited to
      five neurons, all of which were located in the buccal ganglion. Five GABAli-THli
      cells were also observed in the buccal ganglia of two other intensively studied
      panpulmonate species, Lymnaea stagnalis and Helisoma trivolvis. These findings
      indicate that colocalization of the classical neurotransmitters GABA and DA in
      feeding central pattern generator (CPG) interneurons preceded the divergence of
      euopisthobranch and panpulmonate taxa. These observations also support the
      hypothesis that heterogastropod feeding CPG networks exhibit a common universal
      design.

PMID- 29633266
TI  - Variation in expression and activity pattern of mmp2 and mmp9 on different time
      scales in the regenerating caudal fin of Poecilia latipinna.
AB  - Alteration in the expression pattern of matrix metalloproteinase (MMP)2 and MMP9
      was studied in the regenerating caudal fin of Poecilia latipinna immediately
      following amputation until the new tissues gained structural integrity. Timed
      expression pattern of these two MMPs was studied at enzyme, transcript as well as
      protein levels. Additionally, both the gelatinases were localized in the
      regenerating caudal fin during three specific stages of regeneration. The results
      revealed a progressive increase in the expression of MMP2 starting at 1 h post
      amputation (hpa), indicating its possible role in the remodelling of
      extracellular matrix early on during caudal-fin regeneration. Nevertheless, a
      reduction in transcript level expression of MMP2 at 6 hpa and 12 hpa stages,
      points towards a possible transcriptional regulation, to further moderate its
      activity. As observed in the case of MMP2, expression of MMP9 too increased from
      1 hpa and remained elevated until 5 dpa. However, the active MMP9 revealed its
      presence only 12 hpa onwards. Moreover, both the gelatinases were localised in
      the apical epithelial cap and in the progress zone at wound epithelium (1 dpa)
      and blastema (60 hpa) stages respectively. Further, during early differentiation
      stage (5 dpa), high intensities of MMP2 and MMP9 were localized in the newly
      formed actinotrichia as compared with the tissue proximal to it. Based on the
      results, it could be construed that the controlled up-regulation of MMP2 and MMP9
      from 1 hpa until the early differentiation stage ensures a regulated digestion of
      extracellular matrix, perhaps to facilitate the recruitment, proliferation,
      morphogenesis and re-patterning of resident stem cells during caudal fin
      regeneration in P. latipinna.

PMID- 29633267
TI  - Investigating nurses' quality of life and work-life balance statuses in
      Singapore.
AB  - AIMS: To investigate the key determinants of nurses' quality of life and work
      life balance statuses in a tertiary hospital in Singapore. BACKGROUND: Nurses'
      quality of life can directly and indirectly impact patients' safety and quality
      of care. Therefore, identifying key factors that influence nurses' quality of
      life is essential in the healthcare delivery system. METHODS: A descriptive
      quantitative study design was adopted, and validated questionnaires were used.
      Data were collected in a period of 3 months (March to May 2014) at a 600-bed
      tertiary hospital in Singapore. One thousand and forty nurses participated in the
      study. RESULTS: Social support and sense of coherence were found to be
      significant predictors for high quality of life in all domains. Most nurses in
      this study spent more time on work than their private lives. However, there was
      no significant difference in job satisfaction among the four groups of nurses'
      proportions of percentages of actual time spent on work and private life.
      CONCLUSIONS: Cultivating social support from family, friends/colleagues and
      supervisors can help an individual cope with stress and enhance a nurse's quality
      of life. IMPLICATIONS FOR NURSING POLICY AND PRACTICE: Even though nurses who
      spent more time at work were still satisfied with their job, they might need to
      be aware of their physical health and work environment. Nursing policy related to
      nurses' physical health and environment should be established. Health promotion
      programmes such as physical exercise and mindfulness interventions should be
      conducted to promote nurses' well-being and healthy workplace environments to
      enhance nurses' quality of life.

PMID- 29633268
TI  - Comparison of two different surgical approaches to increase peri-implant mucosal
      thickness: A randomized controlled clinical trial.
AB  - BACKGROUND: Current evidence supports the positive effect of adequate peri
      implant mucosal thickness (PMT) on both marginal bone level stability and
      esthetic outcomes. While the subepithelial connective tissue graft (sCTG) has
      been traditionally considered as the gold standard for peri-implant mucosal
      augmentation, acellular dermal matrix (ADM) may be a valid alternative. The
      primary aim of this randomized clinical trial was to determine the clinical
      efficacy of ADM in the augmentation of PMT as compared to an autologous sCTG.
      METHODS: Patients who could benefit from peri-implant mucosal augmentation at the
      time of implant placement were recruited. Participants were randomized to the
      control (simultaneous sCTG) or test (simultaneous ADM) group. The primary outcome
      in this study was changes in PMT between baseline and 16 weeks later. Keratinized
      mucosal width (KMW) changes, modified wound healing index (MWHI) variations and
      patient-reported outcome measures (PROMs) were recorded, as well. RESULTS: A
      total of 20 participants were recruited per an a priori power analysis. There
      were no statistically significant differences between groups at baseline for any
      of the parameters analyzed. The gain in PMT at 1 mm, 3 mm, and 5 mm from the
      expected mucosal margin was 0.44 +/- 2.04 mm, 1.20 +/- 1.48 mm, and 1.20 +/- 0.89
      mm in the sCTG group, and 0.05 +/- 1.57 mm, 0.85 +/- 1.29 mm, and 1.45 +/- 1.17
      mm in the ADM group. No statistically significant differences in terms of PMT,
      KMW, and MWHI changes were observed between groups. The perceived discomfort was
      higher at 2 and 4 weeks for patients in the sCTG group. CONCLUSION: ADM produces
      similar outcomes to sCTG in terms of mucosal augmentation at the time of implant
      placement.

PMID- 29633269
TI  - Effects of lidocaine and the inclusion complex with 2-hydroxypropyl-beta
      cyclodextrin on cell viability and proliferation of oral squamous cell carcinoma.
AB  - OBJECTIVES: Squamous cell carcinoma (SCC) is a malignant disease that affects the
      oral cavity. Lidocaine has shown antiproliferative and cytotoxic activity on
      several cell types. The rapid dispersion is a limitation issue; however, the
      complexation in cyclodextrin improved pharmacological features and modified the
      drug release. This study investigated the effects of lidocaine (lido) complexed
      with 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD-lido) on cell viability and
      proliferation of human tongue squamous cell carcinoma SCC9 and SCC25. METHODS:
      The complex formation was confirmed by differential scanning calorimetry (DSC)
      and scanning electron microscopy (SEM). Cells SCC9 and SCC25 were exposed to lido
      and HP-beta-CD-lido (40-4000 MUm), and the effects on cell viability (MTT) and
      antiproliferative activity (SRB) were tested. KEY FINDINGS: Differential scanning
      calorimetry and SEM results demonstrated the occurrence of host-guest
      interaction. Lido and HP-beta-CD-lido (4000 MUm) significantly reduced the
      viability of SCC9 cells to 83% and 63%, respectively. The viability of SCC25
      treated with lido, and HP-beta-CD-lido (4000 MUm) was 71% and 44%, respectively.
      Lido (4000 MUm) reduced the proliferation of SCC9 and SCC25 to 39.5% and 23.7%,
      respectively. HP-beta-CD-lido (4000 MUm) was cytotoxic for both cell lines.
      CONCLUSIONS: HP-beta-CD was able to potentiate the in vitro cytotoxic effects of
      lidocaine on human squamous cell carcinoma.

PMID- 29633270
TI  - Is the demonstration of bioequivalence for clavulanic acid required in
      amoxicillin-clavulanic acid orally administered immediate-release products?
AB  - OBJECTIVES: Bioequivalence (BE) criteria for amoxicillin-clavulanic acid (Co
      amoxiclav) oral formulations are based on 90% confidence interval for both
      amoxicillin and clavulanic acid. The aim of this work is to explore the relevance
      of demonstrating BE of clavulanic acid in Co-amoxiclav oral formulations and also
      to assess the impact on safety and efficacy of product due to bioinequivalent
      clavulanic acid. METHODS AND KEY FINDINGS: The subtherapeutic levels of
      clavulanic acid would continue to exert their action against beta-lactamases due
      to postbeta-lactamase inhibitor effect. Additionally, only minute quantities are
      required to inhibit beta-lactamases. Majority of adverse effects associated with
      Co-amoxiclav are of less serious nature, therefore, risk due to suprabioavailable
      clavulanic acid was determined to be low. 'Very rapid clavulanic acid release' in
      in vitro dissolution test would ensure that clinically significant differences
      between test and reference formulations if any are detected in advance. As an
      additional risk mitigation strategy, WHO recommends qualitative and quantitative
      composition similarity between test and reference formulations to ensure
      excipients do not adversely impact bioavailability. CONCLUSIONS: Co-amoxiclav
      with non-bioequivalent clavulanic acid, but bioequivalent amoxicillin would still
      achieve its therapeutic objectives without exposing patients to unwanted adverse
      effects. Therefore, the current regulatory criterion of demonstrating BE of
      clavulanic acid appears conservative.

PMID- 29633271
TI  - Psychosocial interventions for disruptive behaviour problems in children in low-
      and middle-income countries: a systematic review and meta-analysis.
AB  - BACKGROUND: Most of the evidence for psychosocial interventions for disruptive
      behaviour problems comes from Western, high-income countries. The transferability
      of this evidence to culturally diverse, low-resource settings with few mental
      health specialists is unknown. METHODS: We conducted a systematic review with
      random-effects meta-analysis of randomized controlled trials examining the
      effects of psychosocial interventions on reducing behaviour problems among
      children (under 18) living in low- and middle-income countries (LMIC). RESULTS:
      Twenty-six randomized controlled trials (representing 28 psychosocial
      interventions), evaluating 4,441 subjects, met selection criteria. Fifteen (54%)
      prevention interventions targeted general or at-risk populations, whereas 13
      (46%) treatment interventions targeted children selected for elevated behaviour
      problems. Most interventions were delivered in group settings (96%) and half
      (50%) were administered by non-specialist providers. The overall effect
      (standardized mean difference, SMD) of prevention studies was -0.25 (95%
      confidence interval (CI): -0.41 to -0.09; I2 : 78%) and of treatment studies was 
      0.56 (95% CI: -0.51 to -0.24; I2 : 74%). Subgroup analyses demonstrated
      effectiveness for child-focused (SMD: -0.35; 95% CI: -0.57 to -0.14) and
      behavioural parenting interventions (SMD: -0.43; 95% CI: -0.66 to -0.20), and
      that interventions were effective across age ranges. CONCLUSIONS: Our meta
      analysis supports the use of psychosocial interventions as a feasible and
      effective way to reduce disruptive behaviour problems among children in LMIC. Our
      study provides strong evidence for child-focused and behavioural parenting
      interventions, interventions across age ranges and interventions delivered in
      groups. Additional research is needed on training and supervision of non
      specialists and on implementation of effective interventions in LMIC settings.

PMID- 29633272
TI  - Effects of FGF-23-mediated ERK/MAPK signaling pathway on parathyroid hormone
      secretion of parathyroid cells in rats with secondary hyperparathyroidism.
AB  - This study is supposed to investigate the effect of FGF-23 on parathyroid hormone
      (PTH) secretion through ERK/MAPK signaling pathway in secondary
      hyperparathyroidism (SHPT) rat model. Thirty rats were equally served as the
      normal and SHPT groups. After transfection, parathyroid cells was assigned into
      blank, NC, pcDNA3.1-FGF-23, siRNA-FGF-23, U0126, and siRNA-FGF-23 + U0126 groups.
      The serum levels of Calcium (Ca), Phosphorus (P), alkaline phosphatase (ALP), and
      PTH were detected. HE and immunohistochemical (IHC) staining were used for the
      histopathological changes and the FGF-23, EKR1/2, and pEKR1/2 expressions. qRT
      PCR and Western blotting were performed to determine the mRNA and protein
      expression of FGF-23, PTH, MAPK, EKR1/2, and Klotho. The proliferation,
      apoptosis, and cell cycle were all measured for parathyroid cells by CCK-8 assay,
      TUNEL staining and Flow cytometry. Compared with the normal group, the SHPT group
      showed increased serum levels PTH, P, ALP, and FGF-23 and mRNA and protein
      expressions of FGF-23 and PTH, whereas declined Ca and p-ERK1/2 expression, mRNA
      and protein expression of Klotho, cell apoptosis rate was reduced. Furthermore,
      compared to the blank and NC groups, the pcDNA3.1-FGF-23 and U0126 groups had a
      decreased mRNA expression of Klotho, protein expression of EKR1/2 and Klotho, and
      cell apoptosis rate was down-regulated, whereas the RNA and protein expressions
      of FGF-23 and PTH were up-regulated, and cell proliferation was elevated. The
      opposite results were observed in the siRNA-FGF-23 group. Our study demonstrated
      that FGF-23 could inhibit signaling transduction of ERK/MAPK pathway and
      accelerate the secretion of PTH in rats with SHPT.

PMID- 29633273
TI  - NEAT1 contributes to neuropathic pain development through targeting miR-381/HMGB1
      axis in CCI rat models.
AB  - LncRNAs have been recognized as significant regulators in various diseases
      including neuropathic pain. Although the lncRNA NEAT1 has been reported to be
      involved in multiple cancers, its biological functions in neuropathic pain still
      remain unknown. In our present study, a chronic constriction injury (CCI) rat
      model was established and we found that NEAT1 was greatly upregulated in the
      spinal cord tissues of CCI rats. Knockdown of NEAT1 can repress neuropathic pain
      behaviors including mechanical and thermal hyperalgesia. In addition, NEAT1
      downregulation inhibited neuroinflammation via inhibiting IL-6, IL-1beta, and
      tumor necrosis factor (TNF)-alpha in CCI rats. We also observed that miR-381 was
      decreased significantly in CCI rats. By using bioinformatics analysis, miR-381
      was predicted to be a microRNA target of NEAT1, which indicated a negative
      correlation between miR-381 and NEAT1. Inhibition of NEAT1 can induce miR-381
      expression in CCI rats, which indicated a negative correlation between NEAT1 and
      miR-381. HMGB1, as a downstream target gene of miR-381 was observed to be
      dramatically increased in CCI rats. miR-381 can modulate HMGB1 expression
      negatively and meanwhile, NEAT1 was able to regulate HMGB1 through sponging miR
      381. Downregulation of HMGB1 can inhibit neuropathic pain behaviors which can be
      reversed by miR-381 inhibitors. Taken these together, it was indicated that NEAT1
      can induce neuropathic pain development in CCI rats via regulating miR-381/HMGB1
      axis.

PMID- 29633274
TI  - Ultrastructure aspects of Brycon gouldingi (Teleostei, Characidae) related to
      swimming ability and feeding during larval development.
AB  - The larval ultrastructure of Brycon gouldingi related to swimming and feeding
      from hatching to total yolk absorption is described from scanning electron
      micrographs. Newly hatched larvae (time zero) had no mouth opening, undefined
      optic vesicles, an olfactory plate visible as a shallow depression, rudimentary
      gill arches, neural groove, embryonic fin and a primary neuromast in the dorsal
      region of the head. At the time of yolk absorption, 55 h post hatching, the
      larvae presented an optic vesicle comprising an optic cup and crystalline lens; a
      mouth with tongue, tapered teeth and taste buds; a ciliated olfactory cavity;
      branched gill arches; filled neural groove signalling central nervous system
      development; caudal, pectoral, dorsal and anal fins; and neuromasts distributed
      throughout the head and body. These characters are related to prey capture and
      swimming ability, key aspects of survival during the larval stage. The results of
      this study provide important information for exploitation and aquaculture of B.
      gouldingi.

PMID- 29633275
TI  - Age and growth of migrating tropical eels, Anguilla celebesensis and Anguilla
      marmorata.
AB  - The age and growth of migrating tropical eels, Anguilla celebesensis and Anguilla
      marmorata from central Sulawesi, Indonesia, were examined. Migrating eels (63 A.
      celebesensis and 38 A. marmorata) were obtained from weirs near the Poso Lake
      outlet and non-migrating eels (35 A. celebesensis and 119 A. marmorata) were
      captured by baited hooks, eel pots, scoop net and electro-fishing in the Poso
      River system, Laa River system, Baluga River, Tongku River and Padapu River from
      February 2009 to October 2010. In both species, the proportion of eels with
      opaque otolith edges showed a single peak in July, suggesting that one annulus (a
      pair of translucent and opaque zones) was formed each year in their otoliths.
      Mean +/- s.d. and range of total length (LT ) and age was 785.2 +/- 114.9 (585
      1083) mm and 7.5 +/- 1.6 (5-11) years in migrating female A. celebesensis and
      1132.2 +/- 173.7 (800-1630) mm and 11.6 +/- 3.3 (7-23) years in A. marmorata. The
      age of migrating female eels was negatively correlated with annual growth rate,
      100.7 +/- 17.2 (68.1-145.0) mm year-1 in A. celebesensis and 97.9 +/- 19.3 (66.6
      131.6) mm year-1 in A. marmorata, but there was no significant correlation
      between the LT and annual growth rate in either species. The annual growth rates
      of these female tropical eels were typically higher than those of temperate
      anguillid species, suggesting a latitudinal cline in growth rate in the genus
      Anguilla reflecting the environmental conditions of their growth habitat.

PMID- 29633276
TI  - Culture-expanded mesenchymal stem cell sheets enhance extraction-site alveolar
      bone growth: An animal study.
AB  - BACKGROUND AND OBJECTIVES: Impaired bone formation of the buccal alveolar plate
      after tooth extraction during adolescence increases the difficulty of future
      implant restoration. This study was undertaken to assess the feasibility and
      efficacy of transplanting autogenous scaffold-free culture-expanded mesenchymal
      stem cell (MSC) sheets to the buccal alveolar bone surface to stimulate local
      bone growth. MATERIAL AND METHODS: Mandibular bone marrow was aspirated from 3
      month-old pigs (n = 5), from which MSCs were isolated and culture expanded.
      Triple-layer MSC sheets were then fabricated using temperature-responsive tissue
      culture plates. One month after bone marrow aspirations, the same pigs underwent
      bilateral extraction of mandibular primary molars, immediately followed by
      transplantation of 3 autogenous triple-layer MSC sheets on to the subperiosteal
      buccal alveolar surface of 1 randomly chosen side. The contralateral side
      (control) underwent the same periosteal reflection surgery without receiving MSC
      sheet transplantation. Six weeks later, the animals were killed and specimens
      from both sides were immediately harvested for radiographic and histological
      analysis. Buccal alveolar bone thickness, tissue mineral density (TMD), mineral
      apposition and bone volume fraction (BV/TV) were quantified and compared between
      the MSC sheet and control sides using paired t-tests. RESULTS: Triple-layer MSC
      sheets were reliably fabricated and the majority of cells remained vital before
      transplantation. The thickness of buccal bone tended to increase with MSC sheet
      transplantation (P = .18), with 4 of 5 animals showing an average of 1.82 +/-
      0.73 mm thicker bone on the MSC sheet side than the control side. After being
      normalized by the TMD of intracortical bone, the TMD of surface cortical bone was
      0.5-fold higher on the MSC sheet side than the control side (P < .05). Likewise,
      the BV/TV measurements of the buccal surface region were also 0.4-fold higher on
      the MSC sheet side than the control side (P < .05) after being normalized by
      measurements from the intracortical region. Mineral apposition measurements were
      not different between the 2 sides. CONCLUSION: Mandibular marrow-derived MSCs can
      be fabricated into cell sheets and autogenous transplantation of MSC sheets onto
      the subperiosteal buccal alveolar bone surface at the tooth-extraction site may
      increase local bone density.

PMID- 29633277
TI  - A novel map of the mouse eye for orienting retinal topography in anatomical
      space.
AB  - Functionally distinct retinal ganglion cells have density and size gradients
      across the mouse retina, and some degenerative eye diseases follow topographic
      specific gradients of cell death. Hence, the anatomical orientation of the retina
      with respect to the orbit and head is important for understanding the functional
      anatomy of the retina in both health and disease. However, different research
      groups use different anatomical landmarks to determine retinal orientation
      (dorsal, ventral, temporal, nasal poles). Variations in the accuracy and
      reliability in marking these landmarks during dissection may lead to
      discrepancies in the identification and reporting of retinal topography. The goal
      of this study was to compare the accuracy and reliability of the canthus, rectus
      muscle, and choroid fissure landmarks in reporting retinal orientation. The
      retinal relieving cut angle made from each landmark during dissection was
      calculated based on its relationship to the opsin transition zone (OTZ),
      determined via a custom MATLAB script that aligns retinas from immunostained s
      opsin. The choroid fissure and rectus muscle landmarks were the most accurate and
      reliable, while burn marks using the canthus as a reference were the least. These
      values were used to build an anatomical map that plots various ocular landmarks
      in relationship to one another, to the horizontal semicircular canals, to lambda
      bregma, and to the earth's horizon. Surprisingly, during normal locomotion, the
      mouse's opsin gradient and the horizontal semicircular canals make equivalent 6
      degrees  angles aligning the OTZ near the earth's horizon, a feature which may
      enhance the mouse's ability to visually navigate through its environment.

PMID- 29633278
TI  - Controlling food, controlling relationships: exploring the meanings and dynamics
      of family food practices through the diary-interview approach.
AB  - Potential merits of a social practice perspective for examining the meanings and
      dynamics of family food include moving beyond individual behaviour, and exploring
      how practices emerge, develop and change. However, researchers have struggled to
      encourage reflection on mundane practices, and how to understand associated
      meanings. Drawing on a study of families in South Wales, this article reflects on
      the value of the diary-interview approach in addressing these methodological
      challenges, and aims to explore and understand the dynamics of control across
      family contexts. Contemporary practice theories distinguish between practices as
      'performances' and practices as 'entities' and the diary-interview method
      facilitated an examination of these dimensions. Detailed accounts of daily
      'performances' (through diaries), alongside reflection on underlying contexts and
      'entities' (through interviews), illustrated the entanglement of control,
      practices and context. The article adds further complexity to the concept of
      practice 'bundles' which facilitated an understanding of how food was
      interrelated with other practices - across family contexts and across
      generations. Sociological approaches with a practices perspective at the core,
      offer potential for developing public health interventions by acknowledging: the
      relational meaning of food; the embeddedness of food within everyday practices;
      and the need to consider interventions across a range of policy areas.

PMID- 29633279
TI  - Biological explanations for discordant noninvasive prenatal test results:
      Preliminary data and lessons learned.
AB  - OBJECTIVE: Maternal plasma cell-free DNA (cfDNA) analysis is a powerful screening
      tool for Down syndrome. In a pilot series, we examined biologic causes of
      discordance between the cfDNA test results and the fetal karyotype. We also
      explored the feasibility of obtaining trio biospecimens by using parental
      engagement. METHODS: A convenience sample of women with discordant cfDNA results
      were recruited by their care providers. We provided shipping materials and
      instructions for biospecimen collection. Maternal, newborn, and placental samples
      were examined with droplet digital PCR. RESULTS: Thirteen of 15 women
      successfully had biospecimens obtained remotely. High-quality DNA was extracted
      in 12 of 13 women. Presumed biologic etiologies for discordance were identified
      in 7 of 12 women: 3 cases from additional clinical review (male renal transplant,
      vanishing twin, and colon cancer) and 4 cases from additional laboratory
      investigation using droplet digital PCR (3 with confined placental mosaicism and
      1 with true fetal mosaicism). CONCLUSIONS: Understanding the biology behind cfDNA
      fetal karyotype discordancy is useful for follow-up clinical care. Our study
      suggests that most cases could be resolved by using a trio biospecimen protocol
      and parental involvement. To improve accuracy, additional sequencing of
      biospecimens will be required.

PMID- 29633281
TI  - Improved survival for extremity soft tissue sarcoma treated in high-volume
      facilities.
AB  - BACKGROUND AND OBJECTIVES: The purpose of this investigation was to determine the
      effect of hospital volume on treatment decisions, treatment results, and overall
      patient survival in extremity soft tissue sarcoma. METHODS: The National Cancer
      Database was used to identify patients >=18 years of age with non-metastatic soft
      tissue sarcoma of the extremity treated with surgery. Patients in high- and low
      volume centers were matched by propensity score and placed into two equal
      comparative groups of 2437 patients each. RESULTS: Chemotherapy was used at a
      higher rate in high-volume centers (22% vs 17%, P < 0.001) and external beam
      radiation usage was similar (55% vs 52%, P = 0.108). There was a lower incidence
      of positive margins in high-volume centers (12% vs 17%, P < 0.001). There was no
      significant difference in the rates of limb salvage surgery or readmissions at
      high-volume hospitals compared to low-volume. In a multivariate Cox proportional
      hazards model, low-volume facilities demonstrated diminished overall survival at
      all time points (hazard ratio at 5 years = 1.24, 95%CI 1.10-1.39). CONCLUSIONS:
      Treatment at high-volume hospitals was associated with fewer positive margins and
      increased overall survival at 2, 5, and 10 years. Continued efforts should focus
      on optimizing the balance between patient access to specialty care and experience
      of the treating center.

PMID- 29633282
TI  - Visual Evoked Potential Recovery by Subretinal Implantation of Photoelectric Dye
      Coupled Thin Film Retinal Prosthesis in Monkey Eyes With Macular Degeneration.
AB  - Retinal prosthesis or artificial retina is a promising modality of treatment for
      outer retinal degeneration, caused by primary and secondary loss of photoreceptor
      cells, in hereditary retinal dystrophy and age-related macular degeneration,
      respectively. Okayama University-type retinal prosthesis (OUReP) is a
      photoelectric dye-coupled polyethylene film which generates electric potential in
      response to light and stimulates nearby neurons. The dye-coupled films were
      implanted by vitreous surgery in the subretinal space of monkey eyes with macular
      degeneration which had been induced by cobalt chloride injection from the scleral
      side. A pilot 1-month observation study involved 6 monkeys and a pivotal 6-month
      observation study involved 8 monkeys. Of 8 monkeys in 6-month group, 3 monkeys
      underwent dye-coupled film removal at 5 months and were observed further for 1
      month. The amplitude of visual evoked potential which had been reduced by macular
      degeneration did recover at 1 month after film implantation and maintained the
      level at 6 months. Optical coherence tomography showed no retinal detachment, and
      full-field electroretinograms maintained a-wave and b-wave amplitudes, indicative
      of no retinal toxicity. Pathological examinations after 6-month implantation
      showed structural integrity of the inner retinal layer in close apposition to dye
      coupled films. The implanted films which were removed by vitrectomy 5 months
      later showed light-evoked surface electric potentials by scanning Kelvin probe
      measurement. The photoelectric dye-coupled film (OUReP), which serves as a light
      receiver and a displacement current generator in the subretinal space of the eye,
      has a potential for recovering vision in diseases with photoreceptor cell loss,
      such as retinitis pigmentosa and age-related macular degeneration.

PMID- 29633283
TI  - T-cell profiles elicited by Toxoplasma gondii in acutely/chronically infected
      humans.
AB  - Toxoplasma gondii (T. gondii) is an obligate intracellular protozoan parasite
      that can infect almost all warm-blooded species and induce a chronic infection in
      human hosts. The aim of this work was to investigate Th1, Th2, Th17 and Treg
      polarization, induced by four important T. gondii antigens (SAG1, ROP1, GRA8 and
      MAG1) in acutely and chronically infected patients. For this purpose, SAG1, ROP1,
      GRA8 and MAG1 were expressed as recombinant proteins, purified, and used to
      evaluate the proinflammatory and regulatory immune response profiles in
      seropositive and seronegative individuals. Our results show that SAG1 and ROP1
      elicited a proinflammatory profile (INF-gamma, IL-12 and IL-17) in individuals in
      the acute phase, whereas MAG1 and GRA8 induced a regulatory pattern (Treg and TGF
      beta) in chronically infected patients. These results reveal fundamental
      differences in T-cell polarization induced by T. gondii antigens, which could
      have important implications in the immunopathogenesis of the disease and in
      future proposals of therapeutic strategies.

PMID- 29633284
TI  - Spatial fractionation of the dose in heavy ions therapy: An optimization study.
AB  - PURPOSE: The alliance of charged particle therapy and the spatial fractionation
      of the dose, as in minibeam or Grid therapy, is an innovative strategy to improve
      the therapeutic index in the treatment of radioresistant tumors. The aim of this
      work was to assess the optimum irradiation configuration in heavy ion spatially
      fractionated radiotherapy (SFRT) in terms of ion species, beam width, center-to
      center distances, and linear energy transfer (LET), information that could be
      used to guide the design of the future biological experiments. The nuclear
      fragmentation leading to peak and valley regions composed of different secondary
      particles, creates the need for a more complete dosimetric description that the
      classical one in SFRT. METHODS: Monte Carlo simulations (GATE 6.2) were performed
      to evaluate the dose distributions for different ions, beam widths, and spacings.
      We have also assessed the 3D-maps of dose-averaged LET and proposed a new
      parameter, the peak-to-valley-LET ratio, to offer a more thorough physical
      evaluation of the technique. RESULTS: Our results show that beam widths larger
      than 400 MUm are needed in order to keep a ratio between the dose in the entrance
      and the dose in the target of the same order as in conventional irradiations. A
      large ctc distance (3500 MUm) would favor tissue sparing since it provides higher
      PVDR, it leads to a reduced contribution of the heavier nuclear fragments and a
      LET value in the valleys a factor 2 lower than the LET in the ctc leading to
      homogeneous distributions in the target. CONCLUSIONS: Heavy ions MBRT provide
      advantageous dose distributions. Thanks to the reduced lateral scattering, the
      use of submillimetric beams still allows to keep a ratio between the dose in the
      entrance and the dose in the target of the same order as in conventional
      irradiations. Large ctc distances (3500 MUm) should be preferred since they lead
      to valley doses composed of lighter nuclear fragments resulting in a much reduced
      dose-averaged LET values in normal tissue, favoring its preservation. Among the
      different ions species evaluated, Ne stands out as the one leading to the best
      balance between high PVDR and PVLR in normal tissues and high LET values (close
      to 100 keV/MUm) and a favorable oxygen enhancement ratio in the target region.

PMID- 29633285
TI  - Efficient and flexible uptake system for mineral elements in plants.
AB  - Contents Summary 513 I. Introduction 513 II. Efficient uptake system formed by
      influx and efflux transporters of mineral elements 514 III. Polarity of
      transporters for mineral elements 515 IV. Regulation of transporters in response
      to environmental change 515 V. Sensing and signaling pathways regulating the
      uptake of mineral elements 515 VI. Conclusions and perspectives 516
      Acknowledgements 516 References 516 SUMMARY: Mineral elements required for plant
      growth and development must first be taken up by the roots from soil. Plants have
      developed an efficient uptake system for the radial transport of mineral elements
      from soil to central stele through the allocation of various transporters at
      different root cells. These transporters are regulated at transcriptional,
      translational and/or post-translational level to cope with the fluctuation of
      mineral elements in soil. In this insight, we describe an efficient uptake system
      for mineral elements formed by influx and efflux transporters, regulatory
      mechanisms and polarity of these transporters, and sensing and signal pathways,
      in response to spatial and temporal changes of mineral elements in soil. An
      understanding of the mineral element uptake system in different plant species,
      and its regulatory network, will contribute to high and safe crop production
      under varying environments.

PMID- 29633286
TI  - Video-assisted thoracoscopic thoracic duct sealing is inconsistent when performed
      with a bipolar vessel-sealing device in healthy cats.
AB  - OBJECTIVE: To describe a technique for video-assisted thoracoscopic (VATS)
      thoracic duct ligation (TDL) in normal cats with a bipolar vessel-sealing device
      and to assess durability of the seal. STUDY DESIGN: Prospective case series.
      ANIMALS: Six healthy research cats. METHODS: Cats were placed under anesthesia
      for computed tomography lymphangiography (CTLA) to identify thoracic duct
      anatomy. On the basis of CTLA findings, cats were positioned in either right or
      left lateral recumbency for a 3-port VATS TDL. Thoracic duct branches were
      dissected from the aorta after subcutaneous indirect near-infrared fluorescence
      (NIRF) lymphography with indocyanine green was performed to optimize detection. A
      vessel-sealing device was used to seal each thoracic duct in 1 or more locations.
      Postattenuation, indirect NIRF lymphography was repeated to confirm complete
      occlusion of thoracic duct flow. CTLA was repeated in all cats 3 months
      postoperatively. RESULTS: The thoracic duct was surgically approached from the
      right in 3 cats and from the left in 3 cats. A median of 2.5 (range 1-6) TDL seal
      sites were applied. In 2 cats, leakage of chyle was detected during dissection.
      At 3 months postoperatively, CTLA confirmed reestablished chylous flow in 5 of 6
      cats, appearing to occur through recanalization of previously sealed sites rather
      than through development of de novo lymphatic vessels. CONCLUSION: VATS TDL is
      feasible in cats, although the variable and delicate nature of feline thoracic
      duct anatomy should be considered preoperatively. CLINICAL SIGNIFICANCE: Bipolar
      vessel-sealing devices are not a durable modality for thoracic duct sealing in
      healthy cats in a seal only fashion.

PMID- 29633287
TI  - TopP-S: Persistent homology-based multi-task deep neural networks for
      simultaneous predictions of partition coefficient and aqueous solubility.
AB  - Aqueous solubility and partition coefficient are important physical properties of
      small molecules. Accurate theoretical prediction of aqueous solubility and
      partition coefficient plays an important role in drug design and discovery. The
      prediction accuracy depends crucially on molecular descriptors which are
      typically derived from a theoretical understanding of the chemistry and physics
      of small molecules. This work introduces an algebraic topology-based method,
      called element-specific persistent homology (ESPH), as a new representation of
      small molecules that is entirely different from conventional chemical and/or
      physical representations. ESPH describes molecular properties in terms of
      multiscale and multicomponent topological invariants. Such topological
      representation is systematical, comprehensive, and scalable with respect to
      molecular size and composition variations. However, it cannot be literally
      translated into a physical interpretation. Fortunately, it is readily suitable
      for machine learning methods, rendering topological learning algorithms. Due to
      the inherent correlation between solubility and partition coefficient, a uniform
      ESPH representation is developed for both properties, which facilitates multi
      task deep neural networks for their simultaneous predictions. This strategy leads
      to a more accurate prediction of relatively small datasets. A total of six
      datasets is considered in this work to validate the proposed topological and
      multitask deep learning approaches. It is demonstrated that the proposed
      approaches achieve some of the most accurate predictions of aqueous solubility
      and partition coefficient. Our software is available online at
      http://weilab.math.msu.edu/TopP-S/. (c) 2018 Wiley Periodicals, Inc.

PMID- 29633280
TI  - Guinea pig models for translation of the developmental origins of health and
      disease hypothesis into the clinic.
AB  - Over 30 years ago Professor David Barker first proposed the theory that events in
      early life could explain an individual's risk of non-communicable disease in
      later life: the developmental origins of health and disease (DOHaD) hypothesis.
      During the 1990s the validity of the DOHaD hypothesis was extensively tested in a
      number of human populations and the mechanisms underpinning it characterised in a
      range of experimental animal models. Over the past decade, researchers have
      sought to use this mechanistic understanding of DOHaD to develop therapeutic
      interventions during pregnancy and early life to improve adult health. A variety
      of animal models have been used to develop and evaluate interventions, each with
      strengths and limitations. It is becoming apparent that effective translational
      research requires that the animal paradigm selected mirrors the tempo of human
      fetal growth and development as closely as possible so that the effect of a
      perinatal insult and/or therapeutic intervention can be fully assessed. The
      guinea pig is one such animal model that over the past two decades has
      demonstrated itself to be a very useful platform for these important reproductive
      studies. This review highlights similarities in the in utero development between
      humans and guinea pigs, the strengths and limitations of the guinea pig as an
      experimental model of DOHaD and the guinea pig's potential to enhance clinical
      therapeutic innovation to improve human health.

PMID- 29633288
TI  - Measurement of fetal atrioventricular time intervals: A comparison of 3 spectral
      Doppler techniques.
AB  - OBJECTIVE: To establish nomograms for fetal atrioventricular (AV) time intervals
      assessed by 3 different pulsed-wave Doppler techniques: left ventricular inflow
      and outflow tracts (LV in/out), superior vena cava and ascending aorta (SVC/AA),
      and pulmonary artery and pulmonary vein (PA/PV). METHODS: A cross-sectional study
      was performed in 311 normal fetuses divided into 5 groups between 16 and 38
      weeks. Pulsed-wave Doppler-derived AV intervals were measured by interrogation of
      flow in LV in/out, SVC/AA, and PA/PV. Linear regression analyses were performed
      to examine correlations with gestational age (GA) and fetal heart rate (FHR).
      Intraclass correlation coefficients for reproducibility of each method were
      compared. RESULTS: Pulmonary artery and pulmonary vein revealed the longest mean
      AV time intervals (P < .001). The AV intervals in all methods were positively
      correlated with GA (R2  = 0.20-0.36; P < .001) and negatively correlated with FHR
      (R2  = 0.09-0.19; P < .001). The SCV/AA time intervals demonstrated the weakest
      influence of FHR. For LV in/out, SVC/AA, and PA/PV, intraobserver and
      interobserver reliability coefficients showed excellent agreements (all
      intraclass correlation coefficients >= 0.80). CONCLUSION: All pulsed-wave Doppler
      derived AV time intervals increased with advancing GA and decreased with
      increasing FHR. Fetal AV interval measurements can be obtained in a clinically
      viable fashion with excellent reproducibility.

PMID- 29633289
TI  - Exogenous melatonin enhances salt stress tolerance in maize seedlings by
      improving antioxidant and photosynthetic capacity.
AB  - Melatonin (N-acetyl-5-methoxytryptamine) is an important biological hormone in
      many abiotic stress responses and developmental processes. In this study, the
      protective roles of melatonin were investigated by measuring the antioxidant
      defense system and photosynthetic characteristics in maize under salt stress. The
      results indicated that NaCl treatment led to the decrease in plant growth,
      chlorophyll contents and photochemical activity of photosystem II (PSII).
      However, the levels of reactive oxygen species increased significantly under salt
      stress. Meanwhile, we found that application of exogenous melatonin alleviated
      reactive oxygen species burst and protected the photosynthetic activity in maize
      seedlings under salt stress through the activation of antioxidant enzymes. In
      addition, 100 MUM melatonin-treated plants showed high photosynthetic efficiency
      and salinity. Immunoblotting analysis of PSII proteins showed that melatonin
      application alleviated the decline of 34 kDa PSII reaction center protein (D1)
      and the increase of PSII subunit S protein. Taken together, our study promotes
      more comprehensive understanding in the protective effects of exogenous melatonin
      in maize under salt stress, and it may be involved in activation of antioxidant
      enzymes and regulation of PSII proteins.

PMID- 29633290
TI  - Maximising platelet availability by delaying cold storage.
AB  - BACKGROUND AND OBJECTIVES: Cold-stored platelets may be an alternative to
      conventional room temperature (RT) storage. However, cold-stored platelets are
      cleared more rapidly from circulation, reducing their suitability for
      prophylactic transfusion. To minimise wastage, it may be beneficial to store
      platelets conventionally until near expiry (4 days) for prophylactic use,
      transferring them to refrigerated storage to facilitate an extended shelf life,
      reserving the platelets for the treatment of acute bleeding. MATERIALS AND
      METHODS: Two ABO-matched buffy-coat-derived platelets (30% plasma/70% SSP+) were
      pooled and split to produce matched pairs (n = 8 pairs). One unit was stored at 2
      6 degrees C without agitation (day 1 postcollection; cold); the second unit was
      stored at 20-24 degrees C with constant agitation until day 4 then stored at 2-6
      degrees C thereafter (delayed-cold). All units were tested for in vitro quality
      periodically over 21 days. RESULTS: During storage, cold and delayed-cold
      platelets maintained a similar platelet count. While pH and HSR were
      significantly higher in delayed-cold platelets, other metabolic markers,
      including lactate production and glucose consumption, did not differ
      significantly. Furthermore, surface expression of phosphatidylserine and CD62P,
      release of soluble CD62P and microparticles were not significantly different,
      suggesting similar activation profiles. Aggregation responses of delayed-cold
      platelets followed the same trend as cold platelets once transferred to cold
      storage, gradually declining over the storage period. CONCLUSION: The metabolic
      and activation profile of delayed-cold platelets was similar to cold-stored
      platelets. These data suggest that transferring platelets to refrigerated storage
      when near expiry may be a viable option for maximising platelet inventories.

PMID- 29633291
TI  - Proliferation of prostate epithelia induced by IL-6 from stroma reacted with
      Trichomonas vaginalis.
AB  - Benign prostatic hyperplasia (BPH) is characterized by the proliferation of
      stromal and epithelial cell types in the prostate, and interactions between the
      two types of cells. We demonstrated previously that proliferation of prostate
      stromal cells was induced by BPH epithelial cells in response to Trichomonas
      vaginalis (Tv) infection via crosstalk with mast cells. In this study, we
      investigated whether IL-6 released by the proliferating stromal cells in turn
      induce the BPH epithelial cells to multiply. When culture supernatants of the
      proliferating prostate stromal cells were added to BPH epithelial cells, the
      latter multiplied, and expression of cyclin D1, FGF2 and Bcl-2 increased.
      Blocking the IL-6 signalling pathway with anti-IL-6R antibody or JAK1/2 inhibitor
      inhibited the proliferation of the BPH epithelial cells and reduced the
      expression of IL-6, IL-6R and STAT3. Also, epithelial-mesenchymal transition was
      detected in the proliferating BPH epithelial cells. In conclusion, IL-6 released
      from proliferating prostate stromal cells induced by BPH epithelial cells
      infected with Tv in turn induces multiplication of the BPH epithelial cells. This
      result provides first evidence that the inflammatory microenvironment of prostate
      stromal cells resulting from Tv infection induces the proliferation of prostate
      epithelial cells by stromal-epithelial interaction.

PMID- 29633292
TI  - Heartbeat counting is unrelated to heartbeat detection: A comparison of methods
      to quantify interoception.
AB  - Recent research has identified individual differences in interoceptive
      sensitivity as a key source of variation in action, cognition, and emotion. This
      research has relied heavily on a single method for assessing interoceptive
      sensitivity: the accuracy of counting heartbeats while at rest. The validity of
      this method was assessed here by comparing the heartbeat counting (HBC)
      performance of 48 individuals with their heartbeat detection (HBD) performance.
      The HBC task required participants to report the numbers of heartbeats counted
      during brief signaled periods and indexed cardioceptive accuracy by the
      difference between the numbers of reported and actual heartbeats. In the HBD
      task, participants indicated the temporal location of heartbeat sensations
      relative to the onset of ventricular contraction. On each trial, they judged
      whether heartbeat sensations were or were not simultaneous with brief tones
      presented at one of six fixed delays following R waves of the ECG. In this
      method, cardioceptive accuracy or precision was indexed by variability in the
      temporal locations, relative to the R wave, of tones judged to be simultaneous
      with heartbeat sensations. Although intratask correlations indicated that each
      method yielded reliable scores, intertask correlations showed that HBC scores
      were unrelated to HBD scores. These results, which indicate that heartbeat
      detection and heartbeat counting are distinct processes, raise important
      questions about the assessment of interoceptive sensitivity and the involvement
      of this attribute in the psychological processes that have been associated with
      it on the basis of their correlations with HBC performance.

PMID- 29633293
TI  - Applying iPSCs for Preserving Endangered Species and Elucidating the Evolution of
      Mammalian Sex Determination.
AB  - The endangered species Tokudaia osimensis has the unique chromosome constitution
      of 2n = 25, with an XO/XO sex chromosome configuration (2n = 25; XO). There is
      urgency to preserve this species and to elucidate the regulator(s) that can
      discriminate the males and females arising from the indistinguishable sex
      chromosome constitution. However, it is not realistic to examine this rare animal
      species by sacrificing individuals. Recently, true naive induced pluripotent stem
      cells were successfully generated from a female T. osimensis, and the sexual
      plasticity of its germ cells was elucidated. This achievement constitutes the
      basis of an attractive research area, including embryonic fate determination, sex
      determination, and factor(s) that can replace the Y chromosome. In this essay,
      concrete strategies to conserve rare animal species and to reveal their specific
      characteristics using other compatible and abundant animals are proposed.

PMID- 29633294
TI  - Development and validation of a HPLC-UV assay for quantification of levetiracetam
      concentrations in critically ill patients undergoing continuous renal replacement
      therapy.
AB  - Limited clinical data exists on the effects of continuous renal replacement
      therapy (CRRT) on drug pharmacokinetics. A high-performance liquid chromatography
      with ultraviolet detection method was developed and validated to determine
      levetiracetam concentrations in human plasma and CRRT effluent samples. Five
      hundred microliters of human plasma and 250 MUL effluent samples were used to
      quantify levetiracetam. Plasma samples were purified by protein precipitation,
      evaporated under nitrogen gas at room temperature and reconstituted in 50 mm
      potassium dihydrogen phosphate buffer (pH of 4.5). Reverse-phase chromatographic
      separation was achieved within 20 min using a mobile phase eluting gradient of 50
      mm potassium dihydrogen phosphate and acetonitrile. UV detection was set at 195
      nm. The calibration curve was found to be linear over the range of 2-80MUg/mL.
      Inter- and intra-day precisions were < 8% for both plasma and effluent samples.
      The accuracy was determined to be within -12-10% of nominal concentrations. The
      method was selective and sensitive with a lower limit of quantification of 2
      MUg/mL. Overall recovery of levetiracetam from plasma was ~100%. The validated
      assay was successfully applied in a pharmacokinetic study to determine potential
      dose adjustments in patients undergoing CRRT and receiving levetiracetam.

PMID- 29633295
TI  - Determination of corypalmine in mouse blood by UPLC-MS/MS and its application to
      a pharmacokinetic study.
AB  - In this work, a selective and sensitive ultra-performance liquid chromatography
      tandem mass spectrometry method was established and validated for determination
      of corypalmine in mouse blood after oral or intravenous administration. A UPLC
      BEH C18 column was used to separate corypalmine and berberrubine (internal
      standard) at 40 degrees C. The mobile phase was composed of acetonitrile and 10
      mmol/L ammonium acetate (containing 0.1% formic acid) at a flow rate of 0.4
      mL/min, and the total run time was 4.0 min. Electrospray ionization in positive
      ion mode was applied; target fragment ions m/z 342.2 -> 178.0 for corypalmine and
      m/z 322.1 -> 307.0 for berberrubine were identified with multiple reaction
      monitoring mode. The linear range was 1-1000 ng/mL (r > 0.995) and the lower
      limit of quantification for corypalmine in plasma was 1.0 ng/mL. The intra- and
      inter-day precisions were both <14%. The range of accuracy in this method was
      97.5-109.0%. Mean recovery was >69.6%, and the matrix effect was 96.8-107.6%.
      Based on its high sensitivity, specificity and reliability, this method was
      successfully applied to study the pharmacokinetic parameters of corypalmine in
      mouse by oral and intravenous administration, and finally, the bioavailability of
      corypalmine was identified at 4.6%.

PMID- 29633296
TI  - Pharmacological upregulation of prostate-specific membrane antigen (PSMA)
      expression in prostate cancer cells.
AB  - BACKGROUND: Prostate-specific membrane antigen (PSMA)-based imaging and therapy
      are increasingly used for prostate cancer management. However, limitations are a
      low PSMA expression in certain patients. Androgen receptor axis inhibition can
      induce PSMA expression in vitro. We hypothesized that different approved
      compounds upregulate PSMA expression and tested their effect in vitro. METHODS:
      Androgen receptor (AR) expressing prostate cancer (LNCaP) and epithelial prostate
      cells (PNT1A) were treated for 7 days with enzalutamide, dutasteride, rapamycin,
      metformin, lovastatin, and acetylsalicylic acid (ASA). PSMA and AR protein
      expression was assessed using flow cytometry, immunocytochemistry and
      immunoblotting. Furthermore, uptake and internalization of 177 Lu-PSMA-617 was
      performed. RESULTS: Enzalutamide and dutasteride led to a significant (both P <
      0.05) upregulation of PSMA surface levels in LNCaP cells. In addition, treatment
      with rapamycin showed a non-significant trend toward PSMA upregulation. No
      changes were detected after treatment with vehicle, metformin, lovastatin, and
      ASA. Total PSMA protein expression was significantly enhanced after treatment
      with enzalutamide and rapamycin (both P < 0.05), whereas dutasteride led to a non
      significant upregulation. Uptake of 177 Lu-PSMA-617 was significantly increased
      after treatment of LNCaP with enzalutamide, dutasteride, and rapamycin (P <
      0.05). In addition, internalization was significantly increased by enzalutamide
      and rapamycin (P < 0.05), and non-significantly increased by dutasteride.
      CONCLUSION: In conclusion, our data provide new insights into the effect of
      different approved pharmacological compounds that can markedly upregulate PSMA
      expression and radioligand uptake in vitro. Pharmacologically induced PSMA
      expression may prove useful to improve prostate cancer detection and to enhance
      anticancer effects in PSMA-based therapy.

PMID- 29633298
TI  - Severe allergic reaction: A rare complication of ultrasound-guided injection of
      thrombin in a femoral pseudoaneurysm.

PMID- 29633297
TI  - Fluorescence-guided surgery and intervention - An AAPM emerging technology blue
      paper.
AB  - Fluorescence-guided surgery (FGS) and other interventions are rapidly evolving as
      a class of technologically driven interventional approaches in which many
      surgical specialties visualize fluorescent molecular tracers or biomarkers
      through associated cameras or oculars to guide clinical decisions on pathological
      lesion detection and excision/ablation. The technology has been commercialized
      for some specific applications, but also presents technical challenges unique to
      optical imaging that could confound the utility of some interventional procedures
      where real-time decisions must be made. Accordingly, the AAPM has initiated the
      publication of this Blue Paper of The Emerging Technology Working Group (TETAWG)
      and the creation of a Task Group from the Therapy Physics Committee within the
      Treatment Delivery Subcommittee. In describing the relevant issues, this document
      outlines the key parameters, stakeholders, impacts, and outcomes of clinical FGS
      technology and its applications. The presentation is not intended to be
      conclusive, but rather to inform the field of medical physics and stimulate the
      discussions needed in the field with respect to a seemingly low-risk imaging
      technology that has high potential for significant therapeutic impact. This AAPM
      Task Group is working toward consensus around guidelines and standards for
      advancing the field safely and effectively.

PMID- 29633299
TI  - Melanoma underreporting among US dermatopathologists: A pilot study.

PMID- 29633300
TI  - Dermatologic toxicity from immune checkpoint blockade therapy with an
      interstitial granulomatous pattern.
AB  - Immunotherapies targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4)
      and the programmed cell death 1 (PD-1) receptor and its ligand (PD-L1) have
      showed significant therapeutic benefit in patients with clinically advanced solid
      malignancies, including melanoma. However, immune-related adverse events (irAE)
      are common, and novel dermatologic toxicities continue to emerge as more patients
      are treated with immunotherapy. Here we describe a patient treated with
      combination immunotherapy of ipilimumab and pembrolizumab, who developed
      asymptomatic erythematous patches on both legs. Histopathologic examination
      revealed a cutaneous interstitial granulomatous dermatitis. Notably, our patient
      did not require cessation of immunotherapy for these lesions, which subsequently
      remained stable, while the patient's melanoma remained controlled. This case
      expands the dermatologic toxicity profile of immune checkpoint blockade, as
      recognition of such toxicities is critical to optimal patient management.

PMID- 29633301
TI  - Effects of the two types of anorexia nervosa (binge eating/purging and
      restrictive) on bone metabolism in female patients.
AB  - OBJECTIVE: This study compared the profiles of the two types of anorexia nervosa
      (AN; restrictive: AN-R, and binge eating/purging: AN-BP) in terms of body
      composition, gynaecological status, disease history and the potential effects on
      bone metabolism. DESIGN: Two hundred and eighty-six women with AN (21.8 +/- 6.5
      years; 204 AN-R and 82 AN-BP) and 130 age-matched controls (CON; 22.6 +/- 6.8
      years) were enrolled. Areal bone mineral density (aBMD) was determined using DXA
      and resting energy expenditure (REE) was indirectly assessed using calorimetry.
      Markers of bone formation (osteocalcin [OC], procollagen type I N-terminal
      propeptide [PINP] and resorption (type I-C telopeptide breakdown products [CTX])
      and leptin were concomitantly evaluated. RESULTS: Anorexia nervosa patients
      presented an alteration in aBMD and bone turnover. When compared according to
      type, AN-BP were older than AN-R and showed less severe undernutrition, lower CTx
      levels, longer duration of AN, and higher REE levels and aBMD at radius and
      lumbar spine. After adjustment for age, weight and hormonal contraceptive use,
      the aBMD and CTx differences disappeared. In both AN groups, aBMD was positively
      correlated with anthropometric parameters and negatively correlated with
      durations of AN and amenorrhoea, the bone formation markers (OC and PINP) and the
      leptin/fat mass ratio. REE was positively correlated with aBMD in AN-R patients
      only. CONCLUSIONS: This study shows the profiles of AN patients according to AN
      type. However, the impact of the profile characteristics on bone status, although
      significant, was minor and disappeared after multiple adjustments. The positive
      correlation between REE and aBMD reinforces the concept that energy disposal and
      bone metabolism are strongly interdependent.

PMID- 29633302
TI  - Evaluation of sex-by-formulation interaction in bioequivalence studies of
      efavirenz tablets.
AB  - AIMS: The existence of a sex-by-formulation interaction in bioequivalence studies
      implies that the bioequivalence results (i.e., the test/reference ratio of the
      pharmacokinetic parameters) obtained in one sex are not similar to those obtained
      in the other sex. Therefore, results obtained in studies including only males
      would not be representative of the results that would have been obtained in
      females and vice versa. Recently, a sex-by-formulation interaction has been
      reported in a study for efavirenz tablets. The purpose of this paper is to
      investigate whether a sex-by-formulation interaction is actually observed in the
      bioequivalence studies conducted with efavirenz tablets. METHODS: The existence
      of sex-by-formulation interaction was investigated in the two studies conducted
      in our centre, where the same test and reference products were investigated in a
      pilot study with 12 subjects and a pivotal study with 36 subjects. RESULTS: In
      the pilot study, the point estimates for the test/reference ratio of geometrics
      means of Cmax in females and males were more than 20% different (95.42%
      vs.79.38%, i.e., 120.21%), but in a subsequent pivotal study the difference was
      less than 2% (111.14% vs. 109.98%, i.e., 101.66%). CONCLUSIONS: A sex-by
      formulation interaction is suggested in the study with a small sample size, but
      it disappears when the study is repeated with a larger sample size. In
      conclusion, the analysis of subgroups should be conducted with caution when the
      size of the subgroups is not powered to show bioequivalence. There seems to be no
      reason to require bioequivalence studies for efavirenz in both sexes.

PMID- 29633304
TI  - Cost-effectiveness of antiviral treatment after resection in hepatitis B virus
      related hepatocellular carcinoma patients with compensated cirrhosis.
AB  - : Hepatocellular carcinoma (HCC) imposes a heavy disease burden on China due to
      its high morbidity and mortality. China accounts for about 50% of the total new
      cases and deaths worldwide. Most cases are related to hepatitis B virus (HBV)
      infection and are associated with cirrhosis at diagnosis. Antiviral treatment
      with nucleos(t)ide analogues (NAs) after resection in HBV-related HCC can reduce
      recurrence and improve survival. Such treatment is in fact recommended by Chinese
      guidelines. However, cost-effectiveness studies regarding this treatment are
      rare. The objective of this study was to estimate the cost-effectiveness of NA
      treatment after resection in HBV-related HCC patients with compensated cirrhosis.
      A Markov model was constructed to simulate HBV-related HCC patients with
      compensated cirrhosis and detectable HBV DNA, with or without NA treatment after
      resection, followed up over their lifetime. Costs, life expectancy, quality
      adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICER)
      were calculated for each strategy from the societal perspective. The parameters
      of the model were derived from published studies, government documents, and our
      surveys. Sensitivity analyses were used to explore the impact of parameters on
      the uncertainty of the results. NA treatment produced 4.22 QALYs, costing
      $39,898, while non-NA treatment achieved 2.80 QALYs, costing $16,048. The ICER of
      NA treatment versus non-NA treatment was $16,848/QALY, which was between 2 and 3
      times gross domestic product per capita and was therefore deemed cost-effective.
      Probabilistic sensitivity analysis confirmed that NA treatment was cost
      effective, with a probability of 0.852. CONCLUSION: NA treatment after liver
      resection was likely cost-effective in HBV-related HCC patients with compensated
      cirrhosis. (Hepatology 2018).

PMID- 29633303
TI  - Hepatocytes and neutrophils cooperatively suppress bacterial infection by
      differentially regulating lipocalin-2 and neutrophil extracellular traps.
AB  - : Lipocalin-2 (LCN2), also known as neutrophil gelatinase-associated lipocalin
      (NGAL), a key antibacterial protein, is highly elevated in patients with end
      stage liver disease that is often associated with bacterial infection. LCN2 is
      expressed at high levels in both hepatocytes and neutrophils; however, how
      hepatocyte-derived and neutrophil-derived LCN2 cooperate to combat bacterial
      infection remains unclear. Here, by studying hepatocyte-specific and myeloid
      specific Lcn2 knockout mice in two models of systemic and local Klebsiella
      pneumoniae infections, we demonstrated that hepatocytes played a critical role in
      controlling systemic infection by secreting LCN2 protein into the circulation
      following intraperitoneal injection of bacteria, whereas neutrophils were more
      important in combating local lung infection by carrying LCN2 in their specific
      granules to the local infection site following intratracheal intubation of
      bacteria. Both hepatocyte-derived and myeloid cell-derived LCN2 were required
      against bacterial infection in the peritoneal cavity and liver necrotic areas
      following intraperitoneal injection of Klebsiella pneumoniae. LCN2/NGAL protein
      was detected in neutrophil extracellular traps (NETs) in activated neutrophils
      from mice and humans. Disruption of the Lcn2 gene in neutrophils abolished LCN2
      on NETs, whereas deletion of this gene in hepatocytes did not affect LCN2 protein
      on NETs. Genetic deletion of the Lcn2 gene globally or specifically in
      neutrophils did not affect NET formation but reduced the bactericidal effect of
      NETs in vitro. Finally, NGAL-positive NETs were detected in the liver from
      patients with various types of liver diseases. CONCLUSION: Both hepatocytes and
      neutrophils combat bacterial infection through the production of LCN2;
      extracellular LCN2 secreted by hepatocytes limits systemic bacterial infection,
      whereas neutrophils carry LCN2 protein to the local site and against local
      bacterial infection through NETs. (Hepatology 2018).

PMID- 29633305
TI  - A novel DICER1 mutation in familial multinodular goitre.

PMID- 29633306
TI  - Humanitarian nursing with Medecins Sans Frontieres: Foregrounding the listening
      guide as a method for analysing oral history data.
AB  - AIMS: To demonstrate how the listening guide contributed to oral history data
      analysis. To better understand the continuing inclination of nurses to engage in
      humanitarian work, foregrounding the nurses' lives. BACKGROUND: The voice-centred
      relational method or listening guide is a method of qualitative data analysis
      used to analyse oral history data. DESIGN: A conventional approach to oral
      history interviews was adopted; intervention into the "flow" of participants'
      narrative was kept to a minimum. A small number of prompts, how they came into
      nursing, recruitment to, life with and since Medecins Sans Frontieres, were used.
      METHODS: Oral history interviews were conducted with seven nurses who had worked
      for Medecins Sans Frontieres. Interviews were digitally recorded. This paper will
      demonstrate the application of the listening guide to historical data analysis
      and critique its applicability and value. The listening guide advocates four
      readings (listenings) of the text. Firstly, locating the plot in the narrative;
      secondly, actively listening for the use of "I?" ("we", or "you"), the "self" in
      context of the story being told and "I poem" development; thirdly, listening for
      relationships and finally, locating accounts in relation to wider social,
      political and societal contexts. RESULTS: Analysis revealed: "becoming", "being"
      and "leaving" Medecins Sans Frontieres as chronological thematic areas. At one
      extreme creating "I poems" foregrounded individual voices while cross-referencing
      to contemporaneous records of world events locates this in an International
      context. CONCLUSION: It is argued that subjecting historical data to the
      listening guide can enable legitimate, creative exploration and analysis of data.

PMID- 29633307
TI  - Treatment choice, satisfaction and quality of life in patients with Graves'
      disease.
AB  - BACKGROUND: Thyrotoxicosis, most often caused by Graves' disease (GD), when
      treated inadequately may result in premature mortality. There is little consensus
      as to which of the 3 treatment options available - antithyroid drugs (ATD),
      radioactive iodine (RAI) and surgery, is better. AIMS: (i) To assess factors
      involved in treatment choice and treatment satisfaction in patients treated for
      Graves' disease; (ii) To assess quality of life (QoL) following treatment of
      Graves' disease. METHOD: Participants were selected from a prospective study
      cohort assessing thyrotoxicosis incidence and severity. Of the 172 eligible
      patients with Graves' disease, 123 treated patients participated (64% had
      received ATD only, 11% RAI and 25% total thyroidectomy, the latter 2 usually
      after a period of ATD), along with 18 untreated patients with newly diagnosed
      Graves' disease (overall participation rate, 73%). Consented patients completed a
      questionnaire detailing factors involved in treatment choice, QoL and
      satisfaction with treatment. RESULTS: Participants reported that the most
      important factors in choosing a treatment were the following: the effects on
      activities of daily living, concern about use of radioiodine, possibility of
      depression or anxiety, and doctor's recommendations. Satisfaction levels were
      high across all 3 treatment types. QoL 1-year following treatment was higher than
      in untreated patients, and comparable with other international studies.
      CONCLUSIONS: Patient satisfaction with therapy and QoL does not differ by
      treatment type. Therefore, clinical and social factors, in combination with
      patient choice and resource availability, should determine which treatment
      modality patients with Graves' disease should receive.

PMID- 29633308
TI  - Molecular targeting of glutaminase sensitizes ovarian cancer cells to
      chemotherapy.
AB  - Altered metabolism is a reemerging hallmark of tumorigenesis. Increased cell
      proliferation results in metabolic reprogramming to facilitate the needs of the
      rapidly dividing tumor cells. In addition to increased glucose uptake, tumors
      also take up increased levels of glutamine. Some cancers develop a reliance on
      glutamine, and are referred to as "glutamine addicted." These tumors over express
      the enzyme glutaminase which is involved in the first step of glutaminolysis. The
      goal of this study was to determine the effects of combined treatment of the
      glutaminase inhibitor bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl) ethyl
      sulfide (BPTES) with chemotherapy on drug resistant ovarian cancer cells. We
      found that ovarian cancer cells show different dependencies on exogenous
      glutamine. However, regardless of glutamine dependence status, treatment with
      BPTES sensitized both paclitaxel, and cisplatin resistant cancer cell lines to
      chemotherapy by inhibiting cell proliferation. Monotherapy with BPTES alone
      resulted in a significant reduction in the ability of glutamine dependent cancer
      cells to form colonies in a clonogenic assay. In addition, glutamine dependent,
      metastatic cancer cells expressed higher levels of glutaminase 1 (GLS1) isoforms,
      KGA and GAC, than untransformed cells. Moreover, dual targeting of both isoforms
      using siRNA was more effective at sensitizing the cancer cells to cisplatin than
      targeting either GAC or KGA alone. Our results suggest that both GLS1 isoforms
      are important for glutamine dependent ovarian cancer survival, hence, both GLS1
      isoforms should be targeted for therapy in metastatic ovarian cancer therapy.

PMID- 29633309
TI  - Genotype, environment, seeding rate, and top-dressed nitrogen effects on end-use
      quality of modern Nebraska winter wheat.

PMID- 29633310
TI  - Nilotinib induced bone marrow CD34+/lin-Ph+ cells early clearance in newly
      diagnosed CP-chronic myeloid leukemia.

PMID- 29633311
TI  - A case of extensive acquired progressive lymphangioma.
AB  - Acquired progressive lymphangioma (benign lymphangioendothelioma) is a rare
      lymphatic anomaly of unclear pathogenesis. Excision is generally advised for
      local disease, although other therapies have been tried. This report describes a
      unique case of extensive acquired progressive lymphangioma involving the abdomen,
      genitalia, and lower extremity of a 1-year-old boy. Rapid progression and
      multisite involvement required exploration of nonsurgical options for management.

PMID- 29633313
TI  - It's time we added a 20th century page to nursing's history.

PMID- 29633312
TI  - Cardiovascular toxicity in patients with chronic myeloid leukemia treated with
      second-generation tyrosine kinase inhibitors in the real-life practice:
      Identification of risk factors and the role of prophylaxis.

PMID- 29633314
TI  - How much does a blood transfusion cost?

PMID- 29633316
TI  - Laboratory model versus real-world experience: secondary testing of platelets for
      bacterial contamination.

PMID- 29633317
TI  - Chartered planes, rescue trucks, and a Blackhawk.

PMID- 29633318
TI  - The negative secondary test for bacteria in platelet units.

PMID- 29633319
TI  - Response to Trans-2017-0772.R1.

PMID- 29633320
TI  - Quest for the holy grail: pathogen reduction in low-income countries.

PMID- 29633321
TI  - The effect of a standard blood donation on oxygen uptake.

PMID- 29633322
TI  - Oxidative stress-related infantile pyknocytosis with Heinz bodies.

PMID- 29633323
TI  - Nanomaterials in the environment: Behavior, fate, bioavailability, and effects-An
      updated review.
AB  - The present review covers developments in studies of nanomaterials (NMs) in the
      environment since our much cited review in 2008. We discuss novel insights into
      fate and behavior, metrology, transformations, bioavailability, toxicity
      mechanisms, and environmental impacts, with a focus on terrestrial and aquatic
      systems. Overall, the findings were that: 1) despite substantial developments,
      critical gaps remain, in large part due to the lack of analytical, modeling, and
      field capabilities, and also due to the breadth and complexity of the area; 2) a
      key knowledge gap is the lack of data on environmental concentrations and
      dosimetry generally; 3) substantial evidence shows that there are nanospecific
      effects (different from the effects of both ions and larger particles) on the
      environment in terms of fate, bioavailability, and toxicity, but this is not
      consistent for all NMs, species, and relevant processes; 4) a paradigm is
      emerging that NMs are less toxic than equivalent dissolved materials but more
      toxic than the corresponding bulk materials; and 5) translation of incompletely
      understood science into regulation and policy continues to be challenging. There
      is a developing consensus that NMs may pose a relatively low environmental risk,
      but because of uncertainty and lack of data in many areas, definitive conclusions
      cannot be drawn. In addition, this emerging consensus will likely change rapidly
      with qualitative changes in the technology and increased future discharges.
      Environ Toxicol Chem 2018;37:2029-2063. (c) 2018 The Authors. Environmental
      Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.

PMID- 29633324
TI  - Eosinophil and airway nerve interactions in asthma.
AB  - Airway eosinophils are increased in asthma and are especially abundant around
      airway nerves. Nerves control bronchoconstiction and in asthma, airway
      hyperreactivity (where airways contract excessively to inhaled stimuli) develops
      when eosinophils alter both parasympathetic and sensory nerve function.
      Eosinophils release major basic protein, which is an antagonist of inhibitory M2
      muscarinic receptors on parasympathetic nerves. Loss of M2 receptor inhibition
      potentiates parasympathetic nerve-mediated bronchoconstriction. Eosinophils also
      increase sensory nerve responsiveness by lowering neurons' activation threshold,
      stimulating nerve growth, and altering neuropeptide expression. Since sensory
      nerves activate parasympathetic nerves via a central neuronal reflex,
      eosinophils' effects on both sensory and parasympathetic nerves potentiate
      bronchoconstriction. This review explores recent insights into mechanisms and
      effects of eosinophil and airway nerve interactions in asthma.

PMID- 29633325
TI  - Benchmarking working conditions for health and safety in the frontline healthcare
      industry: Perspectives from Australia and Malaysia.
AB  - AIM: To present benchmarks for working conditions in healthcare industries as an
      initial effort into international surveillance. BACKGROUND: The healthcare
      industry is fundamental to sustaining the health of Australians, yet it is under
      immense pressure. Budgets are limited, demands are increasing as are workplace
      injuries and all of these factors compromise patient care. Urgent attention is
      needed to reduce strains on workers and costs in health care, however, little
      work has been done to benchmark psychosocial factors in healthcare working
      conditions in the Asia-Pacific. Intercultural comparisons are important to
      provide an evidence base for public policy. DESIGN: A cross-sectional design was
      used (like other studies of prevalence), including a mixed-methods approach with
      qualitative interviews to better contextualize the results. METHODS: Data on
      psychosocial factors and other work variables were collected from healthcare
      workers in three hospitals in Australia (N = 1,258) and Malaysia (N = 1,125).
      2015 benchmarks were calculated for each variable and comparison was conducted
      via independent samples t tests. Healthcare samples were also compared with
      benchmarks for non-healthcare general working populations from their respective
      countries: Australia (N = 973) and Malaysia (N = 225). FINDINGS: Our study
      benchmarks healthcare working conditions in Australia and Malaysia against the
      general working population, identifying trends that indicate the industry is in
      need of intervention strategies and job redesign initiatives that better support
      psychological health and safety. CONCLUSION: We move toward a better
      understanding of the precursors of psychosocial safety climate in a broader
      context, including similarities and differences between Australia and Malaysia in
      national culture, government occupational health and safety policies and top
      level management practices.

PMID- 29633326
TI  - The patient rationale for seeking HIV PEP: Qualitative results from a nurse-led
      program.
AB  - BACKGROUND: HIV PEP is an intervention to prevent HIV seroconversion among HIV
      negative persons after they have come into contact with the virus. The literature
      suggests PEP is greater than 80% effective at reducing HIV seroconversion. To
      expand access to this prevention strategy, we established a nurse-led PEP program
      in two STI clinics. AIMS: We sought to explore why people seek PEP, and their
      experiences using it. MATERIALS & METHODS: We invited participants who used our
      PEP program to engage in semi-structured qualitative interviews. These were audio
      recorded, transcribed verbatim, and analyzed using the techniques of thematic
      analysis. RESULTS: Twelve men who initiated PEP through our program participated
      in an interview. Thematic analysis of the data identified three themes: (1)
      assessing risk, (2) euphoria and distress, and (3) reducing distress. DISCUSSION:
      Based on our findings, it appears as though instances of condomless sex were
      atypical and unplanned, they occurred due to contextual factors (e.g., consent,
      desire to explore, sexual chemistry/intensity), and they resulted in a state of
      temporary euphoria, which, afterward, transformed into distress (i.e., "feel[ing]
      stupid"). The participants used PEP not only for HIV prevention, but also (and
      perhaps more so) to address their emotional state. PEP used seemed to primarily
      occur to address situations of atypical sexual contact with partners they did not
      "know" or "trust". CONCLUSION: We feel these results help contextualize how
      potential PEP users view HIV risk assessments, and how they determine their need
      for this intervention.

PMID- 29633327
TI  - Development and psychometric appraisal of the Pain Management Self-Efficacy
      Questionnaire.
AB  - AIM: The aim of this study was to develop and psychometrically evaluate the Pain
      Management Self-Efficacy Questionnaire. BACKGROUND: Pain management competence
      and confidence are important in rendering safe and effective patient care.
      However, there is a lack of psychometrically sound instruments measuring pain
      management self-efficacy. DESIGN: Triphasic, prospective psychometric study.
      METHOD: A 55-item Pain Management Self-Efficacy Questionnaire was initially
      developed after extensive theoretical and literature review. The questionnaire
      was evaluated by content experts for content validity and a consensus was
      achieved after two iterations. After pretesting, the Pain Management Self
      Efficacy Questionnaire was distributed to 420 randomly selected pre-graduate
      student nurses and registered nurses from a nursing institution and a tertiary
      hospital. Data collection was conducted from January 2015 - 2016. Assessment
      parameters included basic item analysis, reliability analysis, floor and ceiling
      effects and construct validity using factor analysis and "known groups"
      technique. Replication analyses scrutinized two random halves of the sample.
      RESULTS: The initial 55-item questionnaire was reduced to 42 items after two
      iterations of validation. After preliminary factor analyses, the Pain Management
      Self-Efficacy Questionnaire was reduced to 21 items. Final factor analysis
      produced a three-factor model: Comprehensive, Evaluative and Supplemental Pain
      Management Self-Efficacy. Construct validation using Kruskal-Wallis and Mann
      Whitney tests showed group differences according to years of clinical experience
      and receipt of pain management training. CONCLUSION: The 21-item Pain Management
      Self-Efficacy Questionnaire demonstrated satisfactory psychometric properties and
      can be used to measure pain management self-efficacy among nurses. Nevertheless,
      further psychometric validation is warranted accounting differences in culture
      and clinical practices.

PMID- 29633328
TI  - Efficacy of the Otago Exercise Programme to reduce falls in community-dwelling
      adults aged 65-80 years old when delivered as group or individual training.
AB  - AIM: This study will compare how falls can be reduced in non-institutionalized
      older Spanish adults aged 65-80 years by providing group or individual exercise
      sessions using the Otago Exercise Programme. BACKGROUND: The Otago Exercise
      Programme is a progressive home-based exercise programme, where trained health
      professionals help people engage in strength, balance and endurance exercises.
      Its format is based on the evidence from four clinical trials. The benefits of
      the Otago Exercise Programme are the same for people who have and have not
      suffered falls and it can also be used for visually impaired people. DESIGN: A
      multicentre, simply blinded, randomized, non-inferiority clinical trial, with two
      arms-group training and individual training-that started in January 2017 and will
      continue until December 2019. METHODS: Each study group has 364 subjects, who
      will take part in four individual or group sessions delivered mainly by nurses
      over an 8-week period, with a reinforcement session 6 months later. Data will be
      collected at baseline and after 6 and 12 months. The fall percentage will be the
      most relevant clinical variable and we will also consider safety, viability,
      compliance, economic analysis and therapeutic value. Approval and funding was
      granted in December 2016 for this 3-year study by the Spanish Health Research
      Fund (PI16CIII/00031). DISCUSSION: Older people from 65-80 years old tend to be
      more isolated and tackling worries about falls can improve social activities and
      independence. It has been shown that group training provides better adherence to
      exercise than individual training and this study will test that hypothesis for
      the Otago Exercise Programme.

PMID- 29633329
TI  - Apocrine hidrocystoma on the genitalia of a 9-year-old girl.
AB  - Apocrine hidrocystomas are mostly found on the cheeks and eyelids but also on the
      scalp and neck. The age distribution is from 30 to 70 years old. We report a case
      of an apocrine hidrocystoma on the genitalia of a 9-year-old girl.

PMID- 29633331
TI  - Compound heterozygous mutations in desmoplakin associated with skin fragility,
      follicular hyperkeratosis, alopecia, and nail dystrophy.
AB  - Desmoplakin mutations are associated with a wide variety of phenotypes affecting
      the skin, nails, hair, and heart. A 21-month-old boy was born with multiple
      erosions resembling epidermolysis bullosa, complete alopecia, nail dystrophy,
      palmoplantar keratoderma, and areas of follicular hyperkeratosis. He was found to
      have two heterozygous mutations in the desmoplakin gene: c.478 C>T in exon 4
      (p.Arg160X) and c.3630T>A in exon 23 (Tyr1210X). This case expands the clinical
      spectrum associated with desmoplakin mutations and highlights a mutation in exon
      23 that has not been previously reported in the literature.

PMID- 29633332
TI  - Idiopathic facial aseptic granuloma-A diagnostic challenge in pediatric
      dermatology.
AB  - Idiopathic facial aseptic granuloma is a distinct, benign lesion that presents in
      very young children and is characterized by a painless facial nodule that usually
      appears on the cheek. It is typically characterized by a prolonged course but
      heals spontaneously or in response to antibiotic treatment. The challenge is to
      diagnose this entity correctly, ideally based on clinical acumen, to avoid
      surgical intervention with facial sutures and the resultant scarring and
      unnecessary treatment interventions. In this article, we discuss three cases of
      idiopathic facial aseptic granuloma to raise awareness and highlight the
      diagnostic challenges and possible link to childhood rosacea.

PMID- 29633330
TI  - Embedded ensemble encoding hypothesis: The role of the "Prepared" cell.
AB  - We here reconsider current theories of neural ensembles in the context of recent
      discoveries about neuronal dendritic physiology. The key physiological
      observation is that the dendritic plateau potential produces sustained
      depolarization of the cell body (amplitude 10-20 mV, duration 200-500 ms). Our
      central hypothesis is that synaptically-evoked dendritic plateau potentials lead
      to a prepared state of a neuron that favors spike generation. The plateau both
      depolarizes the cell toward spike threshold, and provides faster response to
      inputs through a shortened membrane time constant. As a result, the speed of
      synaptic-to-action potential (AP) transfer is faster during the plateau phase.
      Our hypothesis relates the changes from "resting" to "depolarized" neuronal state
      to changes in ensemble dynamics and in network information flow. The plateau
      provides the Prepared state (sustained depolarization of the cell body) with a
      time window of 200-500 ms. During this time, a neuron can tune into ongoing
      network activity and synchronize spiking with other neurons to provide a
      coordinated Active state (robust firing of somatic APs), which would permit
      "binding" of signals through coordination of neural activity across a population.
      The transient Active ensemble of neurons is embedded in the longer-lasting
      Prepared ensemble of neurons. We hypothesize that "embedded ensemble encoding"
      may be an important organizing principle in networks of neurons.

PMID- 29633333
TI  - Occult dysraphism presenting with acro-osteolysis.
AB  - The skin and the nervous system share common embryologic origins. Cutaneous
      stigmata may be early clues to underlying occult spinal dysraphism. The delayed
      manifestations of spinal dysraphism may also involve the skin. We report a case
      of a 4-year-old child in whom acro-osteolysis and cutaneous trophic changes on
      the right foot were the presenting features of occult dysraphism.

PMID- 29633334
TI  - Ischemic stroke in cancer patients: A review of an underappreciated pathology.
AB  - Currently 1 in 10 patients with ischemic stroke have comorbid cancer, and this
      frequency is expected to increase with continued advances in cancer therapeutics
      prolonging median survival. Well known for its association with venous
      thrombosis, cancer has recently emerged as a significant risk factor for arterial
      thromboembolism, including stroke; however, the underlying mechanisms are
      uncertain. In addition, the optimal strategies to prevent and acutely treat
      stroke in cancer patients are yet to be established. This review summarizes the
      current evidence on ischemic stroke risk, biomarkers, pathophysiology,
      treatments, and prognosis in cancer patients, emphasizing knowledge gaps and the
      potential strategies to address them. Ann Neurol 2018;83:873-883.

PMID- 29633335
TI  - Altered fecal microbiota composition in all male aggressor-exposed rodent model
      simulating features of post-traumatic stress disorder.
AB  - The bidirectional role of gut-brain axis that integrates the gut and central
      nervous system activities has recently been investigated. We studied "cage-within
      cage resident-intruder" all-male model, where subject male mice (C57BL/6J) are
      exposed to aggressor mice (SJL albino), and gut microbiota-derived metabolites
      were identified in plasma after 10 days of exposure. We assessed 16S ribosomal
      RNA gene from fecal samples collected daily from these mice during the 10-day
      study. Alpha diversity using Chao indices indicated no change in diversity in
      aggressor-exposed samples. The abundance profile showed the top phyla were
      Firmicutes and Bacteroidetes, Tenericutes, Verrucomicrobia, Actinobacteria and
      Proteobacteria, respectively. The phyla Firmicutes and Bacteroidetes are
      vulnerable to PTSD-eliciting stress and the Firmicutes/Bacteroidetes ratio
      increases with stress. Principal coordinate analysis showed the control and
      aggressor-exposed samples cluster separately where samples from early time points
      (day 1-3) clustered together and were distinct from late time points (day 4-9).
      The genus-based analysis revealed all control time points clustered together and
      aggressor-exposed samples had multiple clusters. The decrease in proportion of
      Firmicutes after aggressor exposure persisted throughout the study. The
      proportion of Verrucomicrobia immediately decreased and was significantly shifted
      at most of the later time points. The genus Oscillospira, Lactobacillus,
      Akkermansia and Anaeroplasma are the top four genera that differed between
      control and stressor-exposed mice. The data showed immediate effect on microbiome
      composition during a 10 day time period of stress exposure. Studying the
      longitudinal effects of a stressor is an important step toward an improved
      mechanistic understanding of the microbiome dynamics.

PMID- 29633337
TI  - Establishing priorities on the range of conditions managed by UK community
      practitioner nurse prescribers: A modified Delphi consensus study.
AB  - AIM: To provide national consensus on the range of conditions community
      practitioner nurse prescribers manage and for which it is considered important
      that they can prescribe. BACKGROUND: Around 35,000 community practitioner nurse
      prescribers in the United Kingdom are able to prescribe from a limited formulary.
      Although prescribing is a key role for these nurses, there has been a decline in
      the numbers of community practitioner nurse prescribers who prescribe. It is
      evident that changing patterns of client and service delivery, changes the role
      of community nurses and the conditions they manage, however, little is known
      about the conditions community practitioner nurse prescribers manage. DESIGN AND
      METHODS: A modified Delphi approach comprising three on-line surveys delivered to
      a national Expert Panel of 89 qualified community practitioner prescribers. Data
      collection took place between January-March 2017. RESULTS: Panelists reached a
      consensus, with consistent high levels of agreement reached, on nineteen
      conditions for which it is believed community practitioner nurse prescribers
      should be able to prescribe. Conditions identified by school nurses (N = 12) and
      health visitors (N = 7) were mainly acutely focused, whereas those identified by
      district nurses (N = 9) and community staff nurses (N = 6) included both long
      term and acute conditions. CONCLUSION: Given the high degree of consensus, this
      list of conditions should influence any decisions about the items community and
      public health nurses should be able to prescribe. The findings should also
      influence the education and training of these nurses.

PMID- 29633336
TI  - Production and characterization of a human lysosomal recombinant iduronate-2
      sulfatase produced in Pichia pastoris.
AB  - Hunter syndrome (Mucopolysaccharidosis II, MPS II) is an X-linked lysosomal
      storage disease produced by the deficiency of the lysosomal enzyme iduronate-2
      sulfatase (IDS). Currently, MPS II patients are mainly treated with enzyme
      replacement therapy (ERT) using recombinant enzymes produced in mammalian cells.
      As an alternative, several studies have shown the production of active and
      therapeutic forms of lysosomal proteins in microorganisms. In this paper, we
      report the production and characterization of a recombinant IDS produced in the
      yeast Pichia pastoris (prIDS). We evaluated the effect of culture conditions and
      gene sequence optimization on prIDS production. The results showed that the
      highest production of prIDS was obtained at oxygen-limited conditions using a
      codon-optimized IDS cDNA. The purified enzyme showed a final activity of 12.45
      nmol mg-1 H-1 and an apparent molecular mass of about 90 kDa. The highest
      stability was achieved at pH 6.0, and prIDS also showed high stability in human
      serum. Noteworthy, the enzyme was taken up by culture cells in a dose-dependent
      manner through mannose receptors, which allowed the delivery of the enzyme to the
      lysosome. In summary, these results show the potential of Pichia pastoris as a
      host to produce an IDS intended for a MPS II ERT.

PMID- 29633338
TI  - Inhibiting focal adhesion kinase (FAK) blocks IL-4 induced VCAM-1 expression and
      eosinophil recruitment in vitro and in vivo.
AB  - Leukocyte recruitment plays a critical role during both normal inflammation and
      chronic inflammatory diseases, and ongoing studies endeavor to better understand
      the complexities of this process. Focal adhesion kinase (FAK) is well known for
      its role in cancer, yet it also has been shown to regulate aspects of neutrophil
      and B16 melanoma cell recruitment by rapidly influencing endothelial cell focal
      adhesion dynamics and junctional opening. Recently, we found that FAK related non
      kinase (FRNK), a protein that is often used as a FAK dominant negative, blocked
      eosinophil transmigration by preventing the transcription of vascular cell
      adhesion molecule-1 (VCAM-1) and eotaxin-3 (CCL26). Surprisingly, the blocking
      occurred even in the absence of endogenous FAK. To better understand the role of
      FAK in leukocyte recruitment, we used a FAK-specific inhibitor (PF-573228) and
      determined the effect on IL-4 induced eosinophil recruitment in vitro and in
      vivo. PF-573228 prevented the expression of VCAM-1 and CCL26 expression in IL-4
      stimulated human endothelial cells in vitro. As a result, eosinophil adhesion and
      transmigration were blocked. PF-572338 also prevented IL-4-induced VCAM-1
      expression in vivo. Using brightfield intravital microscopy, we found that PF
      573228 decreased leukocyte rolling flux, adhesion, and emigration. We
      specifically examined eosinophil recruitment in vivo by using an eosinophil-GFP
      reporter mouse and found PF-573228 attenuated eosinophil emigration. This study
      reveals that a FAK inhibitor influences inflammation through its action on
      eosinophil recruitment.

PMID- 29633340
TI  - Contribution of adiponectin polymorphisms to the risk of coronary artery disease
      in a North-African Tunisian population.
AB  - BACKGROUND: Adiponectin, an adipocyte-derived protein, is known to play a key
      role in the processes leading to atherosclerosis and coronary artery disease
      (CAD) through its anti-atherogenic, anti-inflammatory, antioxidative, and anti
      apoptotic properties. In the current study, we have studied the association of
      two single nucleotide polymorphisms (SNPs) +45 T>G (rs2241766) and +276 G>T
      (rs1501299) of the adiponectin gene with coronary artery disease (CAD) on an
      Arab/North-African population from Tunisia. METHODS: Subjects comprised 277
      patients with angiographically demonstrated CAD and 269 age- and gender-matched
      control subjects. The adiponectin genotypes were performed by polymerase chain
      reaction-restriction fragment length polymorphism analysis (PCR-RFLP). The
      contribution of adiponectin variants to CAD was analyzed by haplotype and
      regression analysis. RESULTS: Adiponectin +45T>G and +276G>T genotypic and
      allelic distributions did not show a significant difference between cases and
      controls. Similarly, no association with CAD was observed for the haplotype
      analysis. Assuming dominant model of transmission for both polymorphisms and
      after adjustment of a number of traditional risk factors for CAD, logistic
      regression analysis showed an association of SNP +45 T>G with increased risk of
      developing CAD [adjusted OR (95% CI) = 2.59 (1.17-5.70); P = .01]. However, SNP +
      276 G>T is associated with decreased risk of developing CAD [adjusted OR (95% CI)
      = 0.47 (0.22-0.97); P = .04]. CONCLUSION: There is no allelic or genotypic
      association of +45 T>G and +276 G>T of the adiponectin gene with CAD in the
      Tunisian population.

PMID- 29633339
TI  - Impact of intraduodenal acetic acid infusion on pancreatic duct cannulation
      during endoscopic retrograde cholangiopancreatography: A double-blind, randomized
      controlled trial.
AB  - BACKGROUND AND AIM: Endoscopic retrograde cholangiopancreatography (ERCP) is
      associated with risk of complications. Methods to facilitate ductal cannulation
      may reduce complications. Intraduodenal acid infusion is a physiological approach
      to stimulate secretin release in human body and may facilitate cannulation. The
      objective of this study was to investigate the effect of intraduodenal acid
      infusion on pancreatic duct cannulation during ERCP. METHODS: It was a single
      center, double-blind, randomized controlled trial. Consecutive patients
      undergoing first ERCP for pancreatic diseases were randomized toreceive 50 mL
      acetic acid intraduodenal infusion at ERCP (acetic acid group) or 50 mL saline
      (control group). The primary outcome, difficult cannulation rate (cannulation
      time >5 min), in the two groups was compared. RESULTS: Two hundred ten patients
      were included in the final analysis (105 in each group). The difficult
      cannulation rate were 39.1% in the control group and 20.9% in the acetic acid
      group, and the difference was statistically significant (P = 0.004). The overall
      successful deep cannulation rate was 89.5% and 85.7%, respectively (P = 0.402).
      The cannulation time was remarkably shortened (182 vs 286 s, P = 0.018), and the
      cannulation attempts were significantly decreased (3.4 vs 4.4, P = 0.008). The
      fluoroscopy time was also significantly reduced (60 vs 86 s, P = 0.028). The
      incidence of post-ERCP pancreatitis and hyperamylasemia was comparable (7.6% vs
      10.5% and 10.5% vs 19.1%, P > 0.05). CONCLUSION: Intraduodenal acetic acid
      infusion can significantly decrease difficult pancreatic cannulation rate,
      facilitate pancreatic duct cannulation, and reduce radiation exposure
      (ClinicalTrials.gov number, NCT02800772).

PMID- 29633341
TI  - Association between left atrial stiffness and aortic plaque thickness in
      hypertensive patients with stroke.
AB  - OBJECTIVE: Our aim was to investigate the relation between left atrial stiffness
      (LASt) and thoracic aortic plaque thickness in hypertensive patients with stroke.
      METHOD: A total of 97 hypertensive patients were recruited (age: 59.2 +/- 7.5
      years), including 56 consecutive patients with undefined stroke and 41 age
      matched hypertensive patients without stroke. Left atrial strain and stiffness
      were measured using speckle tracking echo. Thoracic aortic plaque detection and
      evaluation was performed using transesophageal echocardiography. RESULTS:
      Hypertensive patients with stroke, when compared with those without stroke, had a
      significantly higher LASt value (P < .001). The percentage of plaque 1-4 mm
      thickness were comparable in both groups (23.2% vs 21.9%; P > .05). While the
      percentage of plaque >=4 mm thickness was much higher in hypertensive patients
      with stroke (71.4% vs 4.9%; P < .001). LASt was considerably increased in
      hypertensive group with paroxysmal atrial fibrillation (PAF) when compared to
      hypertensive group without PAF (P < .01). A significant positive correlation was
      found between the LASt and plaque thickness (P < .001). Multivariate analysis
      showed that LASt was the strongest independent predictor for >=4 mm aortic plaque
      thickness (Hazard ratio = 6.153; P < .001). With receiver operating
      characteristic (ROC) curve analysis, LASt > 0.63 was the best cutoff value in
      predicting aortic plaque thickness >= 4 mm. CONCLUSION: Left atrial stiffness was
      significantly associated with aortic plaque thickness >= 4 mm, in hypertensive
      patients with stroke. These finding prevailed the importance of LASt in risk
      stratification of hypertension.

PMID- 29633342
TI  - Hepatobiliary and Pancreatic: Biliary reoperation for recurrent intrahepatic
      stones in patients with polysplenia syndrome.

PMID- 29633343
TI  - Explained variation of excess hazard models.
AB  - The availability of longstanding collection of detailed cancer patient
      information makes multivariable modelling of cancer-specific hazard of death
      appealing. We propose to report variation in survival explained by each variable
      that constitutes these models. We adapted the ranks explained (RE) measure to the
      relative survival data setting, ie, when competing risks of death are accounted
      for through life tables from the general population. RE is calculated at each
      event time. We introduce weights for each death reflecting its probability to be
      a cancer death. RE varies between -1 and +1 and can be reported at given times in
      the follow-up and as a time-varying measure from diagnosis onward. We present an
      application for patients diagnosed with colon or lung cancer in England. The RE
      measure shows reasonable properties and is comparable in both relative and cause
      specific settings. One year after diagnosis, RE for the most complex excess
      hazard models reaches 0.56, 95% CI: 0.54 to 0.58 (0.58 95% CI: 0.56-0.60) and
      0.69, 95% CI: 0.68 to 0.70 (0.67, 95% CI: 0.66-0.69) for lung and colon cancer
      men (women), respectively. Stage at diagnosis accounts for 12.4% (10.8%) of the
      overall variation in survival among lung cancer patients whereas it carries 61.8%
      (53.5%) of the survival variation in colon cancer patients. Variables other than
      performance status for lung cancer (10%) contribute very little to the overall
      explained variation. The proportion of the variation in survival explained by key
      prognostic factors is a crucial information toward understanding the mechanisms
      underpinning cancer survival. The time-varying RE provides insights into patterns
      of influence for strong predictors.

PMID- 29633344
TI  - Identification and characterization of a novel esterase from Thauera sp.
AB  - A novel esterase gene TLip was identified from the strain Thauera sp. and
      expressed at high levels in Escherichia coli. The TLip protein shared the highest
      identity (48%) to esterase TesA from Pseudomonas aeruginosa when compared to
      enzymes with reported properties. Phylogenetic analysis showed that TLip belongs
      to the GDSL family of bacterial lipolytic enzymes. TLip was an alkaline esterase
      with a broad optimal temperature range 37-50  degrees C and an optimal pH of 8.0.
      Substrate specificity assays showed that TLip preferred medium chain p
      nitrophenyl esters (C6 -C12 ). Besides, the activity of TLip was strongly
      inhibited by Cu2+ but greatly enhanced by Triton X-100 and Tween 80.
      Thermostability assay revealed that TLip was stable without loss of activity at
      37  degrees C and still retained 69% activity at 50  degrees C after 2 H of
      incubation. Together, these provided a good candidate for further exploration of
      TLip as a promising biocatalyst in industry.

PMID- 29633345
TI  - Roles of conserved tryptophans in trimerization of HIV-1 membrane-proximal
      external regions: Implications for virucidal design via alchemical free-energy
      molecular simulations.
AB  - The Dual-Action Virolytic Entry Inhibitors, or "DAVEI's," are a class of
      recombinant fusions of a lectin, a linker polypeptide, and a 15-residue fragment
      from the membrane-proximal external region (MPER) of HIV-1 gp41. DAVEI's trigger
      rupture of HIV-1 virions, and the interaction site between DAVEI MPER and HIV-1
      lies in the gp41 component of the envelope glycoprotein Env. Here, we explore the
      hypothesis that DAVEI MPER engages Env gp41 in a mode structurally similar to a
      crystallographic MPER trimer. We used alchemical free-energy perturbation to
      assess the thermodynamic roles of each of the four conserved tryptophan residues
      on each protomer of MPER3 . We found that a W666A mutation had a large positive
      DeltaDeltaG for all three protomers, while W672A had a large positive DeltaDeltaG
      for only two of the three protomers, with the other tryptophans remaining
      unimportant contributors to MPER3 stability. The protomer for which W672 is not
      important is unique in the placement of its W666 sidechain between the other two
      protomers. We show that the unique orientation of this W666 sidechain azimuthally
      rotates its protomer away from the orientation it would have if the trimer were
      symmetric, resulting in the diminished interaction of this W672 with the rest of
      MPER3 . Our findings are consistent with our previous experimental study of W-to
      A mutants of DAVEI. This suggests that DAVEI MPER may engage HIV-1 Env to form a
      mixed trimer state in which one DAVEI MPER forms a trimer by displacing a more
      weakly interacting protomer of the endogenous Env MPER trimer.

PMID- 29633347
TI  - Successful implementation of diabetes audits in Australia: the Australian
      National Diabetes Information Audit and Benchmarking (ANDIAB) initiative.
AB  - AIM: We developed and implemented a national audit and benchmarking programme to
      describe the clinical status of people with diabetes attending specialist
      diabetes services in Australia. METHODS: The Australian National Diabetes
      Information Audit and Benchmarking (ANDIAB) initiative was established as a
      quality audit activity. De-identified data on demographic, clinical, biochemical
      and outcome items were collected from specialist diabetes services across
      Australia to provide cross-sectional data on people with diabetes attending
      specialist centres at least biennially during the years 1998 to 2011. RESULTS: In
      total, 38 155 sets of data were collected over the eight ANDIAB audits. Each
      ANDIAB audit achieved its primary objective to collect, collate, analyse, audit
      and report clinical diabetes data in Australia. Each audit resulted in the
      production of a pooled data report, as well as individual site reports allowing
      comparison and benchmarking against other participating sites. CONCLUSIONS: The
      ANDIAB initiative resulted in the largest cross-sectional national de-identified
      dataset describing the clinical status of people with diabetes attending
      specialist diabetes services in Australia. ANDIAB showed that people treated by
      specialist services had a high burden of diabetes complications. This quality
      audit activity provided a framework to guide planning of healthcare services.

PMID- 29633346
TI  - Frontline Science: Plasma and immunoglobulin G galactosylation associate with HIV
      persistence during antiretroviral therapy.
AB  - Global antibody glycosylation is dynamic and plays critical roles in shaping
      different immunological outcomes and direct antibody functionality during HIV
      infection. However, the relevance of global antibody or plasma glycosylation
      patterns to HIV persistence after antiretroviral therapy (ART) has not been
      characterized. First, we compared glycomes of total plasma and isolated
      immunoglobulin G (IgG) from HIV+ ART-suppressed, HIV+ viremic, and HIV-negative
      individuals. Second, in ART-suppressed individuals, we examined the associations
      between glycomes and (1) levels of cell-associated HIV DNA and RNA in PBMCs and
      isolated CD4+ T cells, (2) CD4 count and CD4%, and (3) expression of CD4+ T-cell
      activation markers. HIV infection is associated with persistent alterations in
      the IgG glycome including decreased levels of disialylated glycans, which is
      associated with a lower anti-inflammatory activity, and increased levels of
      fucosylated glycans, which is associated with lower antibody-dependent cell
      mediated cytotoxicity (ADCC). We also show that levels of certain mono- and
      digalactosylated nonfucosylated glycomic traits (A2G1, A2G2, and A2BG2), which
      have been reported to be associated with higher ADCC and higher anti-inflammatory
      activities, exhibit significant negative correlations with levels of cell
      associated total HIV DNA and HIV RNA in ART-suppressed individuals. Finally,
      levels of certain circulating anti-inflammatory glycans are associated with
      higher levels of CD4 T cells and lower levels of T-cell activation. Our findings
      represent the first proof-of-concept evidence that glycomic alterations, known to
      be associated with differential states of inflammation and ADCC activities, are
      also associated with levels of HIV persistence in the setting of ART suppression.

PMID- 29633350
TI  - Comparative proteome analysis reveals pathogen specific outer membrane proteins
      of Leptospira.
AB  - Proteomes of pathogenic Leptospira interrogans and L. borgpetersenii and the
      saprophytic L. biflexa were filtered through computational tools to identify
      Outer Membrane Proteins (OMPs) that satisfy the required biophysical parameters
      for their presence on the outer membrane. A total of 133, 130, and 144 OMPs were
      identified in L. interrogans, L. borgpetersenii, and L. biflexa, respectively,
      which forms approximately 4% of proteomes. A holistic analysis of transporting
      and pathogenic characteristics of OMPs together with Clusters of Orthologous
      Groups (COGs) among the OMPs and their distribution across 3 species was made and
      put forward a set of 21 candidate OMPs specific to pathogenic leptospires. It is
      also found that proteins homologous to the candidate OMPs were also present in
      other pathogenic species of leptospires. Six OMPs from L. interrogans and 2 from
      L. borgpetersenii observed to have similar COGs while those were not found in any
      intermediate or saprophytic forms. These OMPs appears to have role in infection
      and pathogenesis and useful for anti-leptospiral strategies.

PMID- 29633349
TI  - Effect of metformin on plasma metabolite profile in the Copenhagen Insulin and
      Metformin Therapy (CIMT) trial.
AB  - AIM: Metformin is the first-line treatment for Type 2 diabetes. However, not all
      people benefit from this drug. Our aim was to investigate the effects of
      metformin on the plasma metabolome and whether the pretreatment metabolite
      profile can predict HbA1c outcome. METHODS: Post hoc analysis of the Copenhagen
      Insulin and Metformin Therapy (CIMT) trial, a multicentre study from May 2008 to
      December 2012, was carried out. We used a non-target method to analyse 87 plasma
      metabolites in participants with Type 2 diabetes (n = 370) who were randomized in
      a 1 : 1 ratio to 18 months of metformin or placebo treatment. Metabolites were
      measured by liquid chromatography-mass spectrometry at baseline and at 18-month
      follow-up and the data were analysed using a linear mixed-effect model. RESULTS:
      At baseline, participants who were on metformin before the trial (n = 312) had
      higher levels of leucine/isoleucine and five lysophosphatidylethanolamines
      (LPEs), and lower levels of carnitine and valine compared with metformin-naive
      participants (n = 58). At follow-up, participants randomized to metformin (n =
      188) had elevated levels of leucine/isoleucine and reduced carnitine, tyrosine
      and valine compared with placebo (n = 182). At baseline, participants on
      metformin treatment with the highest levels of carnitine C10:1 and
      leucine/isoleucine had the lowest HbA1c (P-interaction = 0.02 and 0.03,
      respectively). This association was not significant with HbA1c at follow-up.
      CONCLUSIONS: Metformin treatment is associated with decreased levels of valine,
      tyrosine and carnitine, and increased levels of leucine/isoleucine. None of the
      identified metabolites can predict the HbA1c -lowering effect of metformin.
      Further studies of the association between metformin, carnitine and
      leucine/isoleucine are warranted.

PMID- 29633348
TI  - Protozoal coinfection in horses with equine protozoal myeloencephalitis in the
      eastern United States.
AB  - BACKGROUND: Infection by 2 or more protozoa is linked with increased severity of
      disease in marine mammals with protozoan encephalitis. HYPOTHESIS/OBJECTIVES: To
      assess whether horses with equine protozoal myeloencephalitis (EPM) caused by
      Sarcocystis neurona also have evidence of infection with Neospora hughesi or
      Toxoplasma gondii. We hypothesized that horses with EPM would be more likely than
      horses with cervical vertebral stenotic myelopathy (CVSM) to be positive for
      antibodies to multiple protozoan parasites. ANIMALS: One hundred one horses with
      neurologic disease: 49 with EPM and 52 with CVSM. METHODS: Case review. Archived
      serum and cerebrospinal fluid (CSF) from 101 horses were examined. Inclusion
      criteria included neurologic disease, antemortem or postmortem diagnosis of EPM
      or CVSM, and availability of serological results or archived samples for testing.
      Additional testing for antibodies was performed on serum for T. gondii, as well
      as serum and CSF for N. hughesi. RESULTS: Horses with EPM were more likely than
      horses with CVSM to have positive immunologic results for S. neurona on serum
      (95.9% versus 76.9%, P = .0058), CSF (98.0% versus 44.2%, P < .00001), and serum
      : CSF titer ratio (91.8% versus 0%, P < .00001). Positive results for Neospora
      and Toxoplasma were uncommon, with total seroprevalence rates of 12.9% and 14.9%,
      respectively. The proportions of EPM cases testing positive for Neospora and
      Toxoplasma (16% and 12%) were not different from the proportions of CVSM cases
      testing positive (10% and 17%, P = .31 and .47, respectively). CONCLUSION:
      Results do not indicate an important role for protozoal coinfection in EPM in the
      eastern United States.

PMID- 29633351
TI  - Type 2 diabetes mellitus in older people: a brief statement of key principles of
      modern day management including the assessment of frailty. A national
      collaborative stakeholder initiative.
AB  - Rates of population ageing are unprecedented and this, combined with the
      progressive urbanization of lifestyles, has led to a dramatic shift in the
      epidemiology of diabetes towards old age, particularly to those aged 60-79 years.
      Both ageing and diabetes are recognized as important risk factors for the
      development of functional decline and disability. In addition, diabetes is
      associated with a high economic, social and health burden. Traditional
      macrovascular and microvascular complications of diabetes appear to account for
      less than half of the diabetes-related disability observed in older people.
      Despite this, older adults are under-represented in clinical trials. Guidelines
      from organizations such as the National Institute for Health and Care Excellence
      (NICE), the European Association for the Study of Diabetes, and the American
      Diabetes Association acknowledge the need for individualized care, but the
      glycaemic targets that are suggested to constitute good control [HbA1c 53-59
      mmol/mol (7-7.5%)] are too tight for frail older individuals. We present a
      framework for the assessment of older adults and guidelines for the management of
      this population according to their frailty status, with the intention of reducing
      complications and improving quality of life for these people.

PMID- 29633353
TI  - Response to 'Psoriasis patients' preference for an aerosol foam topical
      formulation' by Vender R et al.

PMID- 29633354
TI  - Reply to: pyoderma gangrenosum: a clinical conundrum.

PMID- 29633352
TI  - Wisteria floribunda agglutinin-positive Mac-2-binding protein and type 4 collagen
      7S: useful markers for the diagnosis of significant fibrosis in patients with non
      alcoholic fatty liver disease.
AB  - BACKGROUND AND AIM: The fibrosis stage of liver is associated with the long-term
      outcomes in patients with non-alcoholic fatty liver disease (NAFLD). However,
      significant fibrosis, defined as fibrosis stages 2-4, is associated with an
      elevated risk of progression to severe liver disease; there have been scant
      reports about diagnosing significant fibrosis. We compare the noninvasive method
      and aim to identify appropriate liver fibrosis markers for detecting significant
      fibrosis in NAFLD patients. METHODS: We compared the usefulness of liver fibrosis
      markers (Wisteria floribunda agglutinin-positive Mac-2-binding protein [WFA+ 
      M2BP], type 4 collagen 7S, etc.), clinical scoring systems, and liver stiffness
      measurement obtained using vibration-controlled transient elastography and
      magnetic resonance imaging-based magnetic resonance elastography in the same
      individuals and identified the most appropriate noninvasive method for detecting
      significant fibrosis in 165 patients with liver biopsy-diagnosed NAFLD. RESULTS:
      The area under the receiver operating characteristic curve based on the serum
      cutoff index values of WFA+ -M2BP/the serum levels of type IV collagen 7S for the
      diagnosis of significant fibrosis was 0.832 (95% confidence interval: 0.771
      0.894)/0.837 (95% confidence interval: 0.778-0.898). "WFA+ -M2BP (cutoff index)
      >= 0.83 or type IV collagen 7S >= 5.2 ng/mL" showed a high sensitivity (91.4%)
      and negative predictive value (87.9%) for the diagnosis of significant fibrosis.
      CONCLUSIONS: We showed that serum WFA+ -M2BP or type IV collagen 7S levels serve
      as useful independent markers for detecting significant fibrosis and that use of
      both WFA+ -M2BP and type IV collagen 7S together increased the sensitivity and
      negative predictive value for the diagnosis of liver fibrosis. These results need
      to be validated in larger populations from multiple clinical centers.

PMID- 29633355
TI  - Clinical and dermoscopic characteristics of congenital melanocytic naevi.
AB  - BACKGROUND: Prompted by the limited data, we conducted this study to gather more
      information on dermoscopic features of CN in children, in order to optimize
      clinical care and management. MATERIALS AND METHODS: All children with congenital
      nevi (CN) attending our Pediatric Pigmented Skin Lesion Unit during a 2-year
      period were included in the study. Clinical data were collected, and all children
      underwent clinical and dermoscopic examination. Dermoscopic patterns and specific
      features were recorded. RESULTS: Three hundred and thirty CN were examined in a
      population of 276 children, aged from 6 months to 14 years. The majority (85.14%)
      had only one congenital naevus, and 43.12% had a family history of congenital
      nevi. Children with multiple congenital nevi were more likely to have a positive
      family history of a CN (P = 0.012). Only, in 23 children,
      neurological/developmental abnormalities were reported. Small CN were the
      commonest in our cohort (167) followed by the medium-sized (160), whereas large
      CN (>20 cm) were only three. Thirty-eight CN were located on the volar skin. The
      globular was the commonest dermoscopic pattern, followed by the reticular,
      whereas the parallel furrow pattern was the commonest pattern on palms and soles.
      CN on the trunk were more likely to be globular on the limbs, and reticular and
      homogeneous on the head and neck (P < 0.001). The commonest dermoscopic findings
      were haloed and target globules, blotches and perifollicular hypopigmentation,
      whereas globules and dots around cristae on volar skin. CN located on the limbs
      were more likely to demonstrate an atypical network (P = 0.001) and a target
      network with globules (P = 0.020), whereas haloed and target globules (P <
      0.001), blotches (P = 0.023) and dots (P = 0.004) were found with an increased
      frequency in CN on the trunk. CONCLUSIONS: Given that there is much controversy
      on the management and accurate classification of CN, our findings may provide
      useful information.

PMID- 29633356
TI  - Medically unexplained dermatologic symptoms and psychodermatology.

PMID- 29633357
TI  - "We're at a watershed": The positioning of PhD nurses in clinical practice.
AB  - AIM: The aim of this study was to explore different perspectives on the
      positioning (i.e. the perceived rights and duties) of PhD nurses and how they
      contribute to clinical nursing practice. BACKGROUND: The number of PhD nurses is
      growing worldwide, but we only have little knowledge of what is expected of PhD
      nurses and what their actual impact is in the clinic. DESIGN: The findings of
      this article stem from a qualitative, explorative interview study. METHODS: Semi
      structured interviews were carried out with six PhD nurses, nine nurse colleagues
      and six clinical nurse leaders. Data collection took place from April - June 2016
      in Central Denmark Region. Data were analysed using positioning theory. FINDINGS:
      The PhD nurses were positioned as responsible for implementing evidence-based
      practice in the clinic and in nursing culture as such. Emphasis was put on the
      importance of PhD nurses staying close to the clinic to do practice-based
      research of immediate effect for patient care. CONCLUSION: The study reveals
      several positive effects of PhD nurses in the clinic but also problematizes the
      many and diverse duties they are expected to carry out.

PMID- 29633358
TI  - Basal cell carcinoma: the utility of in vivo and ex vivo confocal microscopy.
AB  - The use of confocal microscopy is possible using two different modalities: first,
      at patient's bedside for a rapid in vivo diagnosis of basal cell carcinoma and
      second, in the operating room directly on freshly excised specimen for a fast ex
      vivo margin-controlled surgery. In the current review, we report the main
      application of confocal microscopy for basal cell carcinoma diagnosis and
      management in both modalities.

PMID- 29633359
TI  - Laser prostate ablation and enucleation: Analysis of a national cohort.
AB  - OBJECTIVE: To compare characteristics and outcomes of benign prostatic
      hyperplasia patients undergoing prostate laser ablation with those undergoing
      laser enucleation using a nationwide cohort. METHODS: Men who underwent prostate
      laser ablation (n=10054) or laser enucleation (n=1705) between 2011 and 2015 were
      identified by the common procedural terminology code as recorded in the National
      Surgical Quality Improvement Program database. Preoperative, intraoperative and
      postoperative parameters were compared between the groups using univariate and
      multivariate analysis. RESULTS: Prostate laser ablation patients were older, had
      more comorbidities and were more likely to have abnormal laboratory values.
      Enucleations were significantly longer and more likely to result in a hospital
      stay >1day. Enucleation patients were also more likely to require a blood
      transfusion postoperatively, but less likely to experience urinary tract
      infection and sepsis on both univariate and multivariate analysis adjusted for
      preoperative and intraoperative factors. CONCLUSIONS: Although laser enucleation
      and prostate laser ablation are both considered minimally invasive techniques,
      significant differences in patient selection, intraoperative factors and
      postoperative complications are identified in this national cohort. The present
      study shows that despite similar outcomes in prospective single-center studies,
      prostate laser ablation and laser enucleation have distinct practice patterns in
      a broader national context.

PMID- 29633360
TI  - Equine embryo research ethics - should we worry?

PMID- 29633361
TI  - World Equine Veterinary Association and Clinical Evidence for the Chinese
      Practitioner.

PMID- 29633363
TI  - The impact of psoriasis on professional life: PsoPRO, a French national survey.
AB  - BACKGROUND: The physical, social and mental burden of psoriasis is well known,
      but its occupational impact has been less investigated. OBJECTIVE: To assess the
      impact of psoriasis on the working life of patients compared with the general
      population. METHODS: A national survey compared people with and without psoriasis
      using online questionnaires. In addition to the demographic, medical and
      professional characteristics, data on recent absenteeism and presenteeism were
      captured using the validated WPAI-PSO questionnaire. RESULTS: The patient sample
      comprised 714 with psoriasis (PsO), including 81 treated with systemic therapies
      (PsoST), and 84 with associated psoriatic arthritis (PsO + PsA). The control
      sample comprised 604 active subjects representative of the French population.
      Compared to controls, the impact of the disease on working life was no greater in
      PsO patients. Conversely, unemployment within the past 5 years and mean number of
      sick leaves within the previous year were more frequent in PsO + PsA. In patients
      with active psoriasis skin lesions, all aspects of the WPAI questionnaire were
      negatively impacted in PsoST and PsO + PsA patients, but not in PsO patients:
      Levels of absenteeism were 3.3% in controls, 5.6% in PsO (NS), 8.3% in PsoST (P <
      0.05) and 13.0% in Ps0 + PsA (P < 0.05); impairment in presenteeism reached
      27.0%, 21.2% (NS), 43.5% (P < 0.05) and 53.2% (P < 0.05), respectively, while
      overall work impairment was 27.9%, 22.2% (NS), 46.3% (P < 0.05) and 57.6% (P <
      0.05), respectively. Nevertheless, a higher proportion of PsoST and PsO + PsA
      patients reported that work was more important than any other activity in their
      life. CONCLUSION: The occupational impact of psoriasis is important and
      significant in patients who receive systemic therapy or have concurrent PsA but
      minimal or absent in other psoriasis patients. The findings show that psoriasis
      patients have a high level of motivation to work.

PMID- 29633364
TI  - Use of drug intoxicated donors for lung transplant: Impact on survival outcomes.
AB  - INTRODUCTION: The number of increasing deaths due to the opioid epidemic has led
      to a potential greater supply of organ donors. There is hesitancy to use drug
      intoxicated donors, and we evaluated their impact on post-transplant survival.
      BACKGROUND: Patients >=18 years of age undergoing lung transplantation and donors
      from whom at least one organ was donated between January 2005 and March 2015 were
      selected from the United Network of Organ Sharing database. Baseline
      characteristics and post-transplant survival were compared between drug
      intoxicated and all other donors. RESULTS: The utilization of drug intoxicated
      donors increased from 1.86% in 2005 to 6.23% in 2014. The 2 study groups had
      similar characteristics including age, gender, and Lung Allocation Score. As
      compared to all other donors, drug intoxicated donors were younger (29.1 +/- 9.4
      vs 34.6 +/- 13.4 years, P < .0001), less likely to be male (52% vs 61%, P <
      .0001), and had a greater smoking history (14% vs 11%, P .04). There was no
      difference in post-lung transplant survival at 1, 3, and 5 years between drug
      intoxicated donors (85%, 64%, and 47%) and non-drug intoxicated donors (83%, 65%,
      and 51%). CONCLUSION: Transplantation utilizing drug intoxicated donor lungs has
      significantly increased over the past decade without significantly impacting post
      transplant survival.

PMID- 29633362
TI  - Response to Letter to the Editor: Do we have to redefine lameness in the era of
      quantitative gait analysis.

PMID- 29633365
TI  - Chronic oral lichenoid erosions revealing haematological malignancies.

PMID- 29633366
TI  - Psoriasis patients' preference for an aerosol foam topical formulation.

PMID- 29633367
TI  - Laser-assisted photodynamic therapy for superficial basal cell carcinoma and
      Bowen's disease: a randomized intrapatient comparison between a continuous and a
      fractional ablative CO2 laser mode.
AB  - BACKGROUND: Laser-assisted photodynamic therapy is being explored as a method to
      enhance efficacy of photodynamic therapy (PDT). OBJECTIVE: To compare a
      continuous (CL) and a fractional (FL) ablative CO2 laser-assisted methyl
      aminolevulinate (MAL) PDT in the management of superficial basal cell carcinoma
      (sBCC) and Bowen's disease (BD). METHODS: Thirty treatment areas in fifteen
      patients with inoperable, histologically verified sBCC or BD received CL or FL
      after intrapatient randomization. Laser treatment was followed by MAL application
      and illumination occurred 3 h later. This treatment was repeated after 2 weeks.
      An equivalence analysis was performed on the primary endpoint efficacy, while
      secondary endpoints pain, side-effects and aesthetics were evaluated using paired
      samples tests. Patients were also asked for their preferred treatment. RESULTS:
      An excellent efficacy of 92.9% (sBCC, 100%; BD, 80%) was found in both CL + PDT
      and FL + PDT after 12 months. Equivalence could not be established. Little pain
      was perceived in most patients during PDT illumination. PDT treatment in FL + PDT
      was less painful, significantly during the second treatment (P = 0.026). Side
      effects were mild to moderate with erythema being the most frequent immediate
      side-effect, followed by oedema, crusting and burning sensation. Pigmentary
      changes occurred in 21% (CL + PDT) to 29% (FL + PDT), and aesthetics were good to
      excellent in all patients. CL + PDT and FL + PDT did not significantly differ in
      side-effects (P = 0.219-1.000) or aesthetics (P = 0.157-1.000). CONCLUSIONS:
      Results in this pilot study support the promising role of laser-assisted PDT.
      Both treatment arms demonstrated the same efficacy as well as comparable side
      effects and aesthetics. PDT illumination was significantly less painful in the FL
      + PDT group, suggesting a preference for FL + PDT. The authors recommend further
      investigation with a larger sample size, a subgroup analysis between sBCC and BD
      and comparison of different treatment protocols before one technique could be
      preferred to another.

PMID- 29633368
TI  - Laser hair removal after surgery vs. surgery alone for the treatment of pilonidal
      cysts: a retrospective case-control study.
AB  - BACKGROUND: Based on the presumed role of hair in pilonidal cyst (PNC)
      pathogenesis, laser epilation has been used to decrease recurrences. However,
      most of the data rely on case reports and uncontrolled series, and the rare
      controlled studies reported conflicting results. The objective of this study was
      to investigate the efficacy of laser hair removal (LHR) to decrease the
      recurrence rate after surgery of PNC vs. surgery alone. METHODS: We conducted a
      retrospective monocentric case-control study in the departments of Pediatric
      Surgery and Laser Center of Dermatology of the University Hospital of Nice in
      France from January 2010 to June 2017. We included all patients with PNC who had
      surgery during the period, and we compared patients who had LHR after surgery to
      those having surgery alone. The main outcome was the prevalence and number of
      recurrences of PNC in each group. RESULTS: Twelve patients - eight treated with
      alexandrite laser and four patients with Nd : YAG - were included in the cases
      group; 29 patients treated with surgery alone were included in the control group.
      The mean and the median number of laser sessions were 4.2 and 5, respectively
      (extremes 1-10). The postsurgical recurrence rate without LHR was 51.7%, and
      their number varied from 1 to 3. A significant decrease in the recurrence rate
      was observed after LHR (8.3%) compared to control group (P < 0.001). The median
      duration before recurrence was 14 months for surgery alone. The median follow-up
      was 18 months (1-30 months) for LHR group and 30 months (6-72 months) for surgery
      alone group. Two patients had abnormal healing or persistent sinus after surgery
      alone compared to none in the group who undergone laser procedure after surgery.
      CONCLUSIONS: Laser hair removal decreases the risk of delayed healing and of
      recurrences of PNL after surgical procedure.

PMID- 29633369
TI  - Fluorescent biological aerosol particles: Concentrations, emissions, and
      exposures in a northern California residence.
AB  - Residences represent an important site for bioaerosol exposure. We studied
      bioaerosol concentrations, emissions, and exposures in a single-family residence
      in northern California with 2 occupants using real-time instrumentation during 2
      monitoring campaigns (8 weeks during August-October 2016 and 5 weeks during
      January-March 2017). Time- and size-resolved fluorescent biological aerosol
      particles (FBAP) and total airborne particles were measured in real time in the
      kitchen using an ultraviolet aerodynamic particle sizer (UVAPS). Time-resolved
      occupancy status, household activity data, air-change rates, and spatial
      distribution of size-resolved particles were also determined throughout the
      house. Occupant activities strongly influenced indoor FBAP levels. Indoor FBAP
      concentrations were an order of magnitude higher when the house was occupied than
      when the house was vacant. Applying an integral material-balance approach,
      geometric mean of total FBAP emissions from human activities observed to perturb
      indoor levels were in the range of 10-50 million particles per event. During the
      summer and winter campaigns, occupants spent an average of 10 and 8.5 hours per
      day, respectively, awake and at home. During these hours, the geometric mean
      daily-averaged FBAP exposure concentration (1-10 MUm diameter) was similar for
      each subject at 40 particles/L for summer and 29 particles/L for winter.

PMID- 29633370
TI  - Increased prevalence of vitamin D deficiency in patients with alopecia areata: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Alopecia areata (AA) is a hair follicle-specific autoimmune disorder.
      Vitamin D deficiency has been associated with various autoimmune disorders for
      its immunomodulatory effects. However, in previous studies, there had been
      inconsistent association found between AA and vitamin D deficiency. OBJECTIVE: To
      demonstrate the differences of the mean serum 25-hydroxyvitamin D level and
      prevalence of vitamin D deficiency between AA patients and non-AA population.
      METHODS: A systematic review and meta-analysis of observational studies on AA and
      serum vitamin D levels and/or prevalence of vitamin D deficiency was performed
      searching MEDLINE, Cochrane, Web of Science and Google Scholar databases.
      RESULTS: In all, 14 studies including a total of 1255 AA subjects and 784 non-AA
      control were analysed. The mean serum 25-hydroxyvitamin D level was significantly
      lower in AA subjects (-8.52 ng/dL; 95% confidential interval; -5.50 to -11.53).
      The AA subjects had higher odds of vitamin D deficiency (odds ratio of 3.89; 2.02
      to 7.49, mean prevalence of 73.8%; 59.1 to 84.6%). However, it was difficult to
      find clear correlation between serum 25-hydroxyvitamin D level and extent of hair
      loss in AA subjects. CONCLUSION: The AA subjects had lower serum 25
      hydroxyvitamin D level, and vitamin D deficiency was highly prevalent compared to
      non-AA controls. Hence, vitamin D deficiency should be assessed in AA patients.
      Furthermore, nutritional supplementation of vitamin D or topical vitamin D
      analogues can be considered for AA patients with vitamin D deficiency. The
      limitation of this study is the highly heterogeneity of the included studies.

PMID- 29633371
TI  - Introducing 'ecoYeast': ecology and communities of yeasts.

PMID- 29633372
TI  - Evaluating the predictive accuracy and the clinical benefit of a nomogram aimed
      to predict survival in node-positive prostate cancer patients: External
      validation on a multi-institutional database.
AB  - OBJECTIVES: To assess the predictive accuracy and the clinical value of a recent
      nomogram predicting cancer-specific mortality-free survival after surgery in pN1
      prostate cancer patients through an external validation. METHODS: We evaluated
      518 prostate cancer patients treated with radical prostatectomy and pelvic lymph
      node dissection with evidence of nodal metastases at final pathology, at 10
      tertiary centers. External validation was carried out using regression
      coefficients of the previously published nomogram. The performance
      characteristics of the model were assessed by quantifying predictive accuracy,
      according to the area under the curve in the receiver operating characteristic
      curve and model calibration. Furthermore, we systematically analyzed the
      specificity, sensitivity, positive predictive value and negative predictive value
      for each nomogram-derived probability cut-off. Finally, we implemented decision
      curve analysis, in order to quantify the nomogram's clinical value in routine
      practice. RESULTS: External validation showed inferior predictive accuracy as
      referred to in the internal validation (65.8% vs 83.3%, respectively). The
      discrimination (area under the curve) of the multivariable model was 66.7% (95%
      CI 60.1-73.0%) by testing with receiver operating characteristic curve analysis.
      The calibration plot showed an overestimation throughout the range of predicted
      cancer-specific mortality-free survival rates probabilities. However, in decision
      curve analysis, the nomogram's use showed a net benefit when compared with the
      scenarios of treating all patients or none. CONCLUSIONS: In an external setting,
      the nomogram showed inferior predictive accuracy and suboptimal calibration
      characteristics as compared to that reported in the original population. However,
      decision curve analysis showed a clinical net benefit, suggesting a clinical
      implication to correctly manage pN1 prostate cancer patients after surgery.

PMID- 29633373
TI  - Secukinumab treatment in new-onset psoriasis: aiming to understand the potential
      for disease modification - rationale and design of the randomized, multicenter
      STEPIn study.
AB  - BACKGROUND: To date, biological treatments have been assessed in subjects with a
      long-term history of psoriasis and previous failures to systemic and topical
      therapies. In rheumatoid arthritis and other immune-mediated inflammatory
      diseases, early intensive systemic treatment prolongs treatment-free remission.
      We hypothesize that, by treating patients with psoriasis early with an effective
      systemic therapy, we may be able to alter the clinical outcome and the natural
      course of the disease. The STEPIn study (NCT03020199) investigates early
      intervention with secukinumab versus narrow-band ultraviolet B (nb-UVB)
      phototherapy in subjects with new-onset psoriasis. OBJECTIVE: To determine
      whether early intervention with either nb-UVB treatment or secukinumab in
      subjects with new-onset plaque psoriasis might modify the natural course of the
      disease. METHODS: One hundred and sixty subjects aged 18-50 years with new-onset
      (<=12 months) moderate-to-severe plaque psoriasis and naive to systemic treatment
      and phototherapy will be randomized to secukinumab 300 mg or nb-UVB. The Main
      Study has two treatment arms: Arm A1, subcutaneous secukinumab 300 mg at
      baseline, Weeks 1, 2, 3 and 4, and every 4 weeks thereafter until and including
      Week 52; Arm B1, one/two cycles of nb-UVB for 12 weeks each (maximum 28-week
      break between cycles). After treatment discontinuation, patients will be followed
      up and monitored for disease activity up to Week 208. A Mechanistic Sub-study
      will assess immunological changes and pathogenic tissue-resident memory T cells
      in skin biopsies. CONCLUSIONS: STEPIn is the first study to investigate whether
      early intensive treatment in new-onset psoriasis can modify the long-term natural
      course of the disease and thus become a novel treatment strategy for patients
      with psoriasis.

PMID- 29633374
TI  - Prostate-specific antigen screening impacts on biochemical recurrence in patients
      with clinically localized prostate cancer.
AB  - OBJECTIVE: To clarify the impact of prostate-specific antigen screening on
      surgical outcomes of prostate cancer. METHODS: Patients who underwent radical
      prostatectomy were divided into two groups according to prostate-specific antigen
      testing opportunity (group 1, prostate-specific antigen screening; group 2, non
      prostate-specific antigen screening). Perioperative clinical characteristics were
      compared using the Wilcoxon rank-sum and chi2 -tests. Cox proportional hazards
      models were used to identify independent predictors of postoperative biochemical
      recurrence-free survival. RESULTS: In total, 798 patients (63.2%) and 464
      patients (36.8%) were categorized into groups 1 and 2, respectively. Group 2
      patients were more likely to have a higher prostate-specific antigen level and
      age at diagnosis and larger prostate volume. Clinical T stage, percentage of
      positive cores and pathological Gleason score did not differ between the groups.
      The 5-year biochemical recurrence-free survival rate was 83.9% for group 1 and
      71.0% for group 2 (P < 0.001). On multivariate analysis, prostate-specific
      antigen testing opportunity (hazard ratio 2.530; P < 0.001) was an independent
      predictive factor for biochemical recurrence after surgery, as well as
      pathological T stage, pathological Gleason score, positive surgical margin and
      lymphovascular invasion. Additional analyses showed that prostate-specific
      antigen screening had a greater impact on biochemical recurrence in a younger
      patients, patients with a high prostate-specific antigen level, large prostate
      volume and D'Amico high risk, and patients meeting the exclusion criteria of the
      Prostate Cancer Research International Active Surveillance study. CONCLUSIONS:
      Detection by screening results in favorable outcomes after surgery. Prostate
      specific antigen screening might contribute to reducing biochemical recurrence in
      patients with localized prostate cancer.

PMID- 29633375
TI  - Epidemiology of skin cancer in the German population: impact of socioeconomic and
      geographic factors.
AB  - BACKGROUND: Skin cancer being the most common cancer in Germany has shown
      increasing incidence in the past decade. Since mostly caused by excessive UV
      exposure, skin cancer is largely related to behaviour. So far, the impact of
      regional and sociodemographic factors on the development of skin cancer in
      Germany is unclear. OBJECTIVES: This study aimed to investigate the association
      of potential predictive factors with the prevalence of skin cancers in Germany.
      METHODS: Nationwide ambulatory care claims data from persons insured in statutory
      health insurances (SHI) with malignant melanoma (MM, ICD-10 C43) and non
      melanocytic skin cancer (NMSC, ICD-10 C44) in the years 2009-2015 were analysed.
      In addition, sociodemographic population data and satellite-based UV and solar
      radiation data were associated. Descriptive and multivariate (spatial)
      statistical analyses (e.g. Bayes' smoothing) were conducted on county level.
      RESULTS: Data from 70.1 million insured persons were analysed. Age-standardized
      prevalences per 100 000 SHI insured persons for MM and NMSC were 284.7 and 1126.9
      in 2009 and 378.5 and 1708.2 in 2015. Marked regional variations were observed
      with prevalences between 32.9% and 51.6%. Multivariate analysis shows among
      others statistically significant positive correlations between higher income and
      education, and MM/NMSC prevalence. CONCLUSION: Prevalence of MM and NMSC in
      Germany shows spatio-temporal dynamics. Our results demonstrate that regional UV
      radiation, sunshine hours and sociodemographic factors have significant impact on
      skin cancer prevalence in Germany. Individual behaviour obviously is a major
      determinant which should be subject to preventive interventions.

PMID- 29633376
TI  - Gulf-Selective Postsynthetic Functionalization of a Soluble Hexabenzoovalene.
AB  - The interest in 2D-annulated polycyclic aromatic hydrocarbons (PAHs) has risen in
      recent years due to promising applications in using PAHs for organic electronics.
      The larger the PAHs, the more insoluble they are, making their characterization
      and especially selective functionalization difficult. Triptycene end-capping has
      been introduced to circumvent the problem of low solubility of a hexabenzoovalene
      (HBO). Additionally, the tendency to form single-crystals for X-ray diffraction
      is preserved. The good solubility of the HBO makes it possible to selectively
      difunctionalize the compound in the "gulf" region to change electronic properties
      of the pi-system, which has been investigated photophysically as well as
      electrochemically.

PMID- 29633377
TI  - Accuracy of dermoscopic criteria for the differentiation between superficial
      basal cell carcinoma and Bowen's disease.
AB  - BACKGROUND: The dermoscopic features of superficial basal cell carcinoma (sBCC)
      and Bowen's disease (BD) have been extensively investigated, and dermoscopy was
      shown to significantly improve their recognition. However, incorrectly diagnosed
      cases still exist, with a considerable number of sBCCs dermoscopically
      interpreted as BD. Our aim was to investigate the dermoscopic variability in sBCC
      and BD on different anatomic sites, to identify potent dermoscopic predictors for
      each diagnosis and to investigate the potential source of the inaccurate clinico
      dermoscopic diagnosis of some sBCCs. METHODS: Dermoscopic images of
      histopathologically diagnosed sBCC and BD were evaluated by three independent
      investigators for the presence of predefined criteria. Subsequently, three
      independent investigators with expertise in dermoscopy classified the tumours as
      sBCC or BD based on the dermoscopic image. Diagnostic accuracy scores were
      calculated and crude and adjusted odds ratios, and 95% confidence intervals were
      calculated by univariate and conditional multivariate logistic regression,
      respectively. RESULTS: A total of 283 lesions were included in the study (194
      sBCCs and 89 BD). The main dermoscopic predictors of BD were dotted vessels (7.5
      fold) and glomerular vessels (12.7-fold). The presence of leaf-like areas/spoke
      wheel areas/concentric structures (OR = 0.027) and arborizing vessels (OR =
      0.065) has predicted sBCC. Multivariate risk factors for sBCC misclassification
      were the location on lower extremities (OR = 5.5), the presence of dotted vessels
      (OR = 59.5) and the presence of large ulceration (OR = 6.4). In contrast, the
      presence of brown-coloured pigmentation was a protective predictor for
      misdiagnosis (OR = 0.007). Finally, a subgroup analysis of lesions located on
      lower extremities revealed two additional potent predictors of sBCC: superficial
      fine telangiectasia (SFT) and whity shiny blotches/strands. CONCLUSIONS: Dotted
      and glomerular vessels are strong predictors of BD. When located on the lower
      extremities, sBCC may also display dotted vessels, rendering its recognition
      problematic. On the latter anatomic site, clinicians should consider SFT and
      whity shiny blotches/strands as additional sBCC predictors.

PMID- 29633378
TI  - Efficiently Photocontrollable or Not? Biological Activity of Photoisomerizable
      Diarylethenes.
AB  - Diarylethene derivatives, the biological activity of which can be reversibly
      changed by irradiation with light of different wavelengths, have shown promise as
      scientific tools and as candidates for photocontrollable drugs. However, examples
      demonstrating efficient photocontrol of their biological activity are still
      relatively rare. This concept article discusses the possible reasons for this
      situation and presents a critical analysis of existing data and hypotheses in
      this field, in order to extract the design principles enabling the construction
      of efficient photocontrollable diarylethene-based molecules. Papers addressing
      biologically relevant interactions between diarylethenes and biomolecules are
      analyzed; however, in most published cases, the efficiency of photocontrol in
      living systems remains to be demonstrated. We hope that this article will
      encourage further discussion of design principles, primarily among
      pharmacologists, synthetic and medicinal chemists.

PMID- 29633379
TI  - Materials and Techniques for Implantable Nutrient Sensing Using Flexible Sensors
      Integrated with Metal-Organic Frameworks.
AB  - The combination of novel materials with flexible electronic technology may yield
      new concepts of flexible electronic devices that effectively detect various
      biological chemicals to facilitate understanding of biological processes and
      conduct health monitoring. This paper demonstrates single- or multichannel
      implantable flexible sensors that are surface modified with conductive metal
      organic frameworks (MOFs) such as copper-MOF and cobalt-MOF with large surface
      area, high porosity, and tunable catalysis capability. The sensors can monitor
      important nutriments such as ascorbicacid, glycine, l-tryptophan (l-Trp), and
      glucose with detection resolutions of 14.97, 0.71, 4.14, and 54.60 * 10-6 m,
      respectively. In addition, they offer sensing capability even under extreme
      deformation and complex surrounding environment with continuous monitoring
      capability for 20 d due to minimized use of biological active chemicals.
      Experiments using live cells and animals indicate that the MOF-modified sensors
      are biologically safe to cells, and can detect l-Trp in blood and interstitial
      fluid. This work represents the first effort in integrating MOFs with flexible
      sensors to achieve highly specific and sensitive implantable electrochemical
      detection and may inspire appearance of more flexible electronic devices with
      enhanced capability in sensing, energy storage, and catalysis using various
      properties of MOFs.

PMID- 29633380
TI  - Dermoscopic features of melanocytic skin lesions in Greek children and
      adolescents and their association with environmental factors and skin types.
AB  - BACKGROUND: Acquired naevi often present in childhood and increase in number and
      size during early and middle life. As naevi represent potential mimickers of
      melanoma, the knowledge of their epidemiologic and morphologic characteristics is
      essential. OBJECTIVE: In this study, we intend to determine the prevalence of
      dermoscopic patterns of naevi, as well their association with environmental and
      constitutional factors. METHODS: Cross-sectional data derived from a population
      based cohort of children and adolescents aged 6-18 years, from 12 different
      schools in Thessaloniki, Greece. For each participant, a consent form and a
      questionnaire were completed, which included data on age, sex, phototype, sun
      sensitivity, sun exposure, sunscreen use and previous sunburn history. All naevi,
      their body distribution, and their dermoscopic patterns were recorded. RESULTS:
      Two thousand and five hundred and five (2505) subjects were enrolled into the
      study (47.8% males and 52.2% females). The mean number of MN counted in a single
      person was 29.11 (SD = +/-23.863). TNC increased continuously with higher age.
      Males were found to have a significantly increased number on the trunk (11.7 +/-
      11.2 and 10.0 +/- 8.7, respectively, P < 0.001) and face and neck (6.2 +/- 5.3
      and 5.1 +/- 4.3, respectively, P < 0.001) while females on the upper (10.3 +/-
      10.1 and 9.3 +/- 9.4, respectively, P = 0.008) and lower extremities (2.8 +/- 3.4
      and 2.5 +/- 3.2, respectively, P = 0.008). Globular pattern was the most frequent
      dominant pattern in lower age groups, and its percentage fell as age increased.
      On the contrary, the reticular pattern was more often documented in individuals
      in adolescence. CONCLUSION: This first study of MN in our young population aims
      to be the basis of further investigation for the MM preventive policy of our
      state.

PMID- 29633381
TI  - Divergence in Ynone Reactivity: Atypical Cyclization by 3,4-Difunctionalization
      versus Rare Bis(cyclization).
AB  - Functionalized ynones can be activated by Tf2 C=CH2 , which was generated in
      situ, to form zwitterionic species. These species were trapped in an
      intramolecular fashion by several nucleophiles to generate two major types of
      triflones in a divergent manner. Through fine-tuning of the reaction temperature,
      bis(triflyl)-6-membered- or (triflyl)-5-membered-fused-heterocycles were achieved
      in reasonable yields in a totally selective manner. In this way,
      bis(triflyl)flavones, bis(triflyl)thioflavones, bis(triflyl)selenoflavones,
      (triflyl)benzothienopyrans, (triflyl)benzoselenophenopyrans, (triflyl)vinyl
      aurones, and (triflyl)pyranoindoles were constructed. Conceivable mechanistic
      pathways were suggested on the basis of the isolation of several intermediates
      and the results from control experiments.

PMID- 29633382
TI  - Healthcare professionals' views of group structured education for people with
      newly diagnosed Type 2 diabetes.
AB  - AIM: To determine healthcare professionals' (HCP) views of group structured
      education for people with newly diagnosed Type 2 diabetes. METHODS: This was a
      qualitative study using semi-structured interviews to ascertain primary care
      HCPs' views and experiences of education for people with newly diagnosed Type 2
      diabetes. A thematic framework method was applied to analyse the data.
      Participants were HCPs (N = 22) from 15 general practices in three south London
      boroughs. RESULTS: All but one HCP viewed diabetes education favourably and all
      identified that low attendance was a problem. Three key themes emerged from the
      qualitative data: (1) benefits of diabetes education, including the group mode of
      delivery, improved patient interactions, saving HCPs' time and improved patient
      outcomes; (2) factors limiting uptake of education, including patient-level
      problems such as access and the appropriateness of the programme for certain
      groups, and difficulties communicating the benefits to patients and integration
      of education management plans into ongoing diabetes care; and (3) suggestions for
      improvement, including strategies to improve attendance at education with more
      localized and targeted marketing and enhanced programme content including follow
      up sessions and support for people with pre-existing psychological issues.
      CONCLUSIONS: Most HCPs valued diabetes education and all highlighted the lack of
      provision for people with different levels of health literacy. Because there was
      wide variation in terms of the level of knowledge regarding the education on
      offer, future studies may want to focus on how to help HCPs encourage their
      patients to attend.

PMID- 29633383
TI  - Efficacy of coloured overlays and lenses for treating reading difficulty: an
      overview of systematic reviews.
AB  - Coloured overlays or lenses are widely available for use by children and adults
      with difficulties or discomfort while reading. In recent years, systematic
      reviews have been conducted in an attempt to establish the strength of the
      evidence base for this intervention. The aim of this overview is to
      systematically review these reviews. The methodology was published prospectively
      as a protocol (Prospero CRD42017059172). Online databases Medline, Cinahl, Embase
      and the Cochrane Library were searched for systematic reviews on the efficacy of
      coloured overlays or lenses for the alleviation of reading difficulty or
      discomfort. Included studies were appraised using the AMSTAR 2 checklist.
      Characteristics of included studies such as aspects of methods, results and
      conclusions were recorded. Both processes were conducted independently by two
      reviewers and any discrepancies were resolved by discussion. Thirty-one studies
      were found via databases and other sources. After excluding duplicates and those
      not fitting the inclusion criteria, four reviews were included in the analysis.
      While all reviews were systematic, their methodology, results and conclusions
      differed. Three of the four concluded that there is insufficient good quality
      evidence to support the use of coloured overlays or lenses for reading
      difficulty, while one concluded that, despite research limitations, the evidence
      does support their use. On balance, systematic reviews to date indicate that
      there is not yet a reliable evidence base on which to recommend coloured overlays
      or lenses for the alleviation of reading difficulty or discomfort. High quality,
      low bias research is needed to investigate their effectiveness in different forms
      of reading difficulty and discomfort for adults and children.

PMID- 29633384
TI  - 3D Hierarchical Microballs Constructed by Intertwined MnO@N-doped Carbon
      Nanofibers towards Superior Lithium-Storage Properties.
AB  - MnO is a promising high-capacity anode material for lithium-ion batteries (LIBs),
      but pristine material suffers short cycle life and poor rate capability, thus
      hindering the practical application. In this work, a new type of porous MnO
      microballs stringed with N-doped porous carbon (3DHB-MnO@NC) with a well
      connected hierarchical three-dimensional network structure was prepared by the
      facile self-template method. The 3DHB-MnO@NC electrode can effectively promote
      the ion/electron transfer and buffer the large volume change of electrode during
      the electrochemical reaction. As the anode for LIBs, the 3DHB-MnO@NC possesses
      outstanding cycling performance (1247.7 mA h g-1 after 90 cycles at 200 mA g-1 )
      and good rate capabilities (949.6 mA h g-1 after 450 cycles at 1000 mA g-1 ). The
      facile self-template method of the prepared 3DHB-MnO@NC composite paves a new way
      for practical applications of MnO in high performance LIBs.

PMID- 29633385
TI  - Deep-Ultraviolet Hyperbolic Metacavity Laser.
AB  - Given the high demand for miniaturized optoelectronic circuits, plasmonic devices
      with the capability of generating coherent radiation at deep subwavelength scales
      have attracted great interest for diverse applications such as nanoantennas,
      single photon sources, and nanosensors. However, the design of such lasing
      devices remains a challenging issue because of the long structure requirements
      for producing strong radiation feedback. Here, a plasmonic laser made by using a
      nanoscale hyperbolic metamaterial cube, called hyperbolic metacavity, on a
      multiple quantum-well (MQW), deep-ultraviolet emitter is presented. The
      specifically designed metacavity merges plasmon resonant modes within the cube
      and provides a unique resonant radiation feedback to the MQW. This unique plasmon
      field allows the dipoles of the MQW with various orientations into radiative
      emission, achieving enhancement of spontaneous emission rate by a factor of 33
      and of quantum efficiency by a factor of 2.5, which is beneficial for coherent
      laser action. The hyperbolic metacavity laser shows a clear clamping of
      spontaneous emission above the threshold, which demonstrates a near complete
      radiation coupling of the MQW with the metacavity. This approach shown here can
      greatly simplify the requirements of plasmonic nanolaser with a long plasmonic
      structure, and the metacavity effect can be extended to many other material
      systems.

PMID- 29633386
TI  - Potent anti-leukemia activities of humanized CD19-targeted Chimeric antigen
      receptor T (CAR-T) cells in patients with relapsed/refractory acute lymphoblastic
      leukemia.
AB  - Chimeric antigen receptor T (CAR-T) cell therapy has shown promising results for
      relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL). The immune response
      induced by murine single-chain variable fragment (scFv) of the CAR may limit CAR
      T cell persistence and thus increases the risk of leukemia relapse. In this
      study, we developed a novel humanized scFv from the murine FMC63 antibody. A
      total of 18 R/R ALL patients with or without prior murine CD19 CAR-T therapy were
      treated with humanized CD19-targeted CAR-T cells (hCART19s). After
      lymphodepletion chemotherapy with cyclophosphamide and fludarabine, the patients
      received a single dose (1 * 106 /kg) of autologous hCART19s infusion. Among the
      14 patients without previous CAR-T therapy, 13 (92.9%) achieved complete
      remission (CR) or CR with incomplete count recovery (CRi) on day 30, whereas 1 of
      the 3 patients who failed a second murine CAR-T infusion achieved CR after
      hCART19s infusion. At day 180, the overall and leukemia-free survival rates were
      65.8% and 71.4%, respectively. The cumulative incidence of relapse was 22.6%, and
      the nonrelapse mortality rate was 7.1%. During treatment, 13 patients developed
      grade 1-2 cytokine release syndrome (CRS), 4 patients developed grade 3-5 CRS,
      and 1 patient experienced reversible neurotoxicity. These results indicated that
      hCART19s could induce remission in patients with R/R B-ALL, especially in
      patients who received a reinfusion of murine CAR-T.

PMID- 29633388
TI  - Acne and nutrition: hypotheses, myths and facts.
AB  - Acne is an inflammatory and multifactorial skin disease. Different external and
      internal factors, including air pollution, aggressive skincare products,
      medication, mechanical, hormonal and familial factors and, more recently,
      lifestyle and stress, have been suggested as having an impact on acne. Moreover,
      for many years nutrition was believed to cause or worsen acne. Over the last
      decades, however, it has become a dermatological doctrine that there is no direct
      association between diet and acne. Even if recent research has allowed to
      identify certain nutritional elements and behaviour that may impact on acne,
      including the excessive intake of dairy products and hyperglycaemic food, modern
      lifestyle nutrition, obesity and eating disorders, knowledge about the role of
      nutrition in the physiopathology of acne still remains sparse and hypotheses and
      myths continue to dominate the debate. Thus, further clinical and translational
      research is necessary to investigate and confirm the association between
      nutrition and acne.

PMID- 29633387
TI  - Variant-specific and reciprocal Hsp40 functions in Hsp104-mediated prion
      elimination.
AB  - The amyloid-based prions of Saccharomyces cerevisiae are heritable aggregates of
      misfolded proteins, passed to daughter cells following fragmentation by molecular
      chaperones including the J-protein Sis1, Hsp70 and Hsp104. Overexpression of
      Hsp104 efficiently cures cell populations of the prion [PSI+ ] by an alternative
      Sis1-dependent mechanism that is currently the subject of significant debate.
      Here, we broadly investigate the role of J-proteins in this process by
      determining the impact of amyloid polymorphisms (prion variants) on the ability
      of well-studied Sis1 constructs to compensate for Sis1 and ask whether any other
      S. cerevisiae cytosolic J-proteins are also required for this process. Our
      comprehensive screen, examining all 13 members of the yeast cytosolic/nuclear J
      protein complement, uncovered significant variant-dependent genetic evidence for
      a role of Apj1 (antiprion DnaJ) in this process. For strong, but not weak [PSI+ ]
      variants, depletion of Apj1 inhibits Hsp104-mediated curing. Overexpression of
      either Apj1 or Sis1 enhances curing, while overexpression of Ydj1 completely
      blocks it. We also demonstrated that Sis1 was the only J-protein necessary for
      the propagation of at least two weak [PSI+ ] variants and no J-protein
      alteration, or even combination of alterations, affected the curing of weak [PSI+
      ] variants, suggesting the possibility of biochemically distinct, variant
      specific Hsp104-mediated curing mechanisms.

PMID- 29633390
TI  - Candida induces the expression of IL-36gamma in human keratinocytes: implications
      for a pathogen-driven exacerbation of psoriasis?

PMID- 29633389
TI  - 12 Weeks of a Ribavirin-Free Sofosbuvir and Nonstructural Protein 5A Inhibitor
      Regimen Is Enough to Treat Recurrence of Hepatitis C After Liver Transplantation.
AB  - : Sofosbuvir (SOF) combined with nonstructural protein 5A (NS5A) inhibitors has
      demonstrated its efficacy in treating a recurrence of hepatitis C virus (HCV)
      after liver transplantation (LT). However, the duration of treatment and need for
      ribavirin (RBV) remain unclear in this population. Our aim was to determine
      whether LT recipients could be treated with an SOF + NS5A inhibitor-based regimen
      without RBV for 12 weeks post-LT. Between October 2013 and December 2015, 699 LT
      recipients experiencing an HCV recurrence were enrolled in the multicenter ANRS
      CO23 CUPILT cohort. We selected patients receiving SOF and NS5A inhibitor +/- RBV
      and followed for at least 12 weeks after treatment discontinuation. The primary
      efficacy endpoint was a sustained virological response 12 weeks after the end of
      treatment (SVR12). Among these 699 patients, 512 fulfilled the inclusion
      criteria. Their main characteristics were: 70.1% genotype 1, 18.2% genotype 3,
      21.1% cirrhosis, and 34.4% previously treated patients. We identified four groups
      of patients according to their treatment and duration: SOF + NS5A without RBV for
      12 (156 patients) or 24 (239 patients) weeks; SOF + NS5A + RBV for 12 (47
      patients) or 24 (70 patients) weeks. SVR12 values reached 94.9%, 97.9%, 95.7%,
      and 92.9%, respectively (P = 0.14). Only 20 patients experienced a treatment
      failure. Under multivariate analysis, factors such as fibrosis stage, previous
      treatment, HCV genotype, and baseline HCV viral load did not influence SVR12
      rates in the four groups (P = 0.21). Hematological adverse events (AEs) were more
      common in the RBV group: anemia (P < 0.0001) and blood transfusion (P = 0.0001).
      CONCLUSION: SOF + NS5A inhibitors without RBV for 12 weeks constituted reliable
      therapy for recurrent HCV post-LT with an excellent SVR12 whatever the fibrosis
      stage, HCV genotype, and previous HCV treatment. (Hepatology 2018; 00:000-000).

PMID- 29633392
TI  - High volume of polysorbate-containing (Tween(r) 80) solutions induces false
      positive results in intradermal test.
AB  - BACKGROUND: Intradermal test is used to detect causative allergens in IgE
      mediated hypersensitivity. The surfactant polysorbate 80 can be added to
      intradermal test solutions to more reliably dissolve the allergen and ensure a
      constant bioavailability of the injected allergen. Polysorbate 80 has, however,
      some histamine-releasing properties which could blur the difference to the
      histamine-induced wheal. Routinely serving as a control. OBJECTIVE: Allergen-free
      polysorbate 80 containing (0.005%) test solutions were therefore systematically
      tested at different injection volumes to see whether polysorbate can falsify skin
      reactions and if yes whether conditions can be identified to avoid this. METHODS:
      In a partly blinded study, 30 patients were tested intracutaneously at the back:
      each received at three separate sites 0.05 mL of polysorbate-containing solvent,
      0.02 mL polysorbate-containing solvent as well as 0.02 mL polysorbate-free
      solvent. After 15 min, wheal and erythema were documented and planimetrically
      quantified. RESULTS: Unexpectedly 23 of 30 (77%) patients showed false-positive
      test reactions to the volume of 0.05 mL of the polysorbate-containing solvent
      whereas the polysorbate-containing solvent with 0.02 mL and the polysorbate-free
      solvent with 0.02 mL injection volume had no reinforcing effect on skin test
      reaction. CONCLUSIONS: Different volumes of polysorbate-containing solutions, all
      recommended by manufacturers for intradermal tests, may significantly influence
      test results. The study shows that a polysorbate 80 used at 0.005% in solvents
      for intradermal test to provide a better bioavailability of allergens produces
      false-positive reactivity in a surprising and a hitherto unknown 77% if the 0.05
      mL volume is injected. It is, therefore, mandatory to strictly adhere to an
      intradermal test volume of 0.02 mL as only then falsifying effects of the
      polysorbate additive are avoided, and comparable test results are ensured.

PMID- 29633391
TI  - The sigma factor sigma54 is required for the long-term survival of Leptospira
      biflexa in water.
AB  - Leptospira spp. comprise both pathogenic and free-living saprophytic species.
      Little is known about the environmental adaptation and survival mechanisms of
      Leptospira. Alternative sigma factor, sigma54 (RpoN) is known to play an
      important role in environmental and host adaptation in many bacteria. In this
      study, we constructed an rpoN mutant by allele exchange, and the complemented
      strain in saprophytic L. biflexa. Transcriptome analysis revealed that expression
      of several genes involved in nitrogen uptake and metabolism, including amtB1,
      glnB-amtB2, ntrX and narK, were controlled by sigma54 . While wild-type L.
      biflexa could not grow under nitrogen-limiting conditions but was able to survive
      under such conditions and recover rapidly, the rpoN mutant was not. The rpoN
      mutant also had dramatically reduced ability to survive long-term in water.
      sigma54 appears to regulate expression of amtB1, glnK-amtB2, ntrX and narK in an
      indirect manner. However, we identified a novel nitrogen-related gene,
      LEPBI_I1011, whose expression was directly under the control of sigma54 (herein
      renamed as rcfA for RpoN-controlled factor A). Taken together, our data reveal
      that the sigma54 regulatory network plays an important role in the long-term
      environmental survival of Leptospira spp.

PMID- 29633393
TI  - Towards the Prediction of Global Solution State Properties for Hydrogen Bonded,
      Self-Associating Amphiphiles.
AB  - Through this extensive structure-property study we show that critical micelle
      concentration correlates with self-associative hydrogen bond complex formation
      constant, when combined with outputs from low level, widely accessible,
      computational models. Herein, we bring together a series of 39 structurally
      related molecules related by stepwise variation of a hydrogen bond donor-acceptor
      amphiphilic salt. The self-associative and corresponding global properties for
      this family of compounds have been studied in the gas, solid and solution states.
      Within the solution state, we have shown the type of self-associated structure
      present to be solvent dependent. In DMSO, this class of compound show a
      preference for hydrogen bonded dimer formation, however moving into aqueous
      solutions the same compounds are found to form larger self-associated aggregates.
      This observation has allowed us the unique opportunity to investigate and begin
      to predict self-association events at both the molecular and extended aggregate
      level.

PMID- 29633394
TI  - For Cryptococcus neoformans, responding to the copper status in a colonization
      niche is not just about copper.
AB  - Most fungi express two transcription factors that regulate the expression of
      genes associated with copper uptake for nutritional needs, and with copper
      resistance when copper approaches a cytotoxic level. These factors are
      characterized by cysteine-rich motifs which are associated with copper-sensing,
      DNA-binding and release, and/or cytoplasmic retention. Cryptococcus neoformans
      differs from most in that it expresses a single such copper-sensing trans-factor,
      Cuf1, a protein that up-regulates copper uptake when copper is scarce, and up
      regulates copper sequestration when cells become super-replete. For C. neoformans
      this is an essential task in as much as copper is relatively bioavailable in lung
      airways while the brain interstitium can be copper-limiting for growth. While
      fungal dependence on and sensitivity to copper have long been considered targets
      for anti-fungal chemistry, fungi have proven adept at finding 'work arounds' by
      using a chelated form of copper as nutrient or adapting to a copper-surfaced
      hospital bed by increased resistance. However, the cohort of Cuf1 targets
      identified in this report represent far more than just the uptake and
      sequestration machinery, but include additional loci that, perhaps, are less
      easily 'defended' by the fungus. Garcia-Santamarina et al. provide that list and
      thus lay the ground-work for developing novel anti-fungal reagents.

PMID- 29633395
TI  - Configurable Integration of On-Chip Quantum Dot Lasers and Subwavelength
      Plasmonic Waveguides.
AB  - The integration of on-chip dielectric lasers and subwavelength plasmonic
      waveguides has attracted enormous attention because of the combination of both
      the advantages of the high performances of the small dielectric lasers and the
      subwavelength plasmonic waveguides. However, the configurable integration is
      still a challenge owing to the complexity of the hybrid structures and the
      damageability of the gain media in the multistep micro/nanofabrications. By
      employing the dark-field optical imaging technique with a position uncertainty of
      about 21 nm and combining the high-resolution electron beam lithography, the
      small colloidal quantum dot (CQD) lasers without any damages are accurately
      aligned with the silver nanowires. As a result, the integration of the CQD lasers
      and the silver nanowires can be flexibly configured on chips. In the experiment,
      the tangential coupling, radial coupling, and complex coupling between the high
      performance CQD lasers and the subwavelength silver nanowires are demonstrated.
      Because of the subwavelength field confinements of the silver nanowires, the deep
      subwavelength coherent sources (multimode, one-color single-mode, or two-color
      single-mode) with a mode area of only 0.008lambda2 are output from these hybrid
      structures. This configurable on-chip integration with high flexibility and
      controllability will greatly facilitate the developments of the complex
      functional hybrid photonic-plasmonic circuits.

PMID- 29633396
TI  - Epoxide Hydrolase Conformational Heterogeneity for the Resolution of Bulky
      Pharmacologically Relevant Epoxide Substrates.
AB  - The conformational landscape of Bacillus megaterium epoxide hydrolase (BmEH) and
      how it is altered by mutations that confer the enzyme the ability to accept bulky
      epoxide substrates has been investigated. Extensive molecular dynamics (MD)
      simulations coupled to active site volume calculations have unveiled relevant
      features of the enzyme conformational dynamics and function. Our long-timescale
      MD simulations identify key conformational states not previously observed by
      means of X-ray crystallography and short MD simulations that present the loop
      containing one of the catalytic residues, Asp239, in a wide-open conformation,
      which is likely involved in the binding of the epoxide substrate. Introduction of
      mutations M145S and F128A dramatically alters the conformational landscape of the
      enzyme. These singly mutated variants can accept bulky epoxide substrates due to
      the disorder induced by mutation in the alpha-helix containing the catalytic
      Tyr144 and some parts of the lid domain. These changes impact the enzyme active
      site, which is substantially wider and more complementary to the bulky
      pharmacologically relevant epoxide substrates.

PMID- 29633397
TI  - A Semitransparent Inorganic Perovskite Film for Overcoming Ultraviolet Light
      Instability of Organic Solar Cells and Achieving 14.03% Efficiency.
AB  - Organic solar cells (OSCs) can be unstable under ultraviolet (UV) irradiation. To
      address this issue and enhance the power conversion efficiency (PCE), an
      inorganic-perovskite/organic four-terminal tandem solar cell (TSC) based on a
      semitransparent inorganic CsPbBr3 perovskite solar cell (pero-SC) as the top cell
      and an OSC as bottom cell is constructed. The high-quality CsPbBr3 photoactive
      layer of the planar pero-SC is prepared with a dual-source vacuum coevaporation
      method, using stoichiometric precursors of CsBr and PbBr2 with a low evaporation
      rate. The resultant opaque planar pero-SC exhibits an ultrahigh open-circuit
      voltage of 1.44 V and the highest reported PCE of 7.78% for a CsPbBr3 -based
      planar pero-SC. Importantly, the devices show no degradation after 120 h UV light
      illumination. The related semitransparent pero-SC can almost completely filter UV
      light and well maintain photovoltaic performance; it additionally shows an
      extremely high average visible transmittance. When it is used to construct a TSC,
      the top pero-SC acting as a UV filter can utilize UV light for photoelectric
      conversion, avoiding the instability problem of UV light on the bottom OSC that
      can meet the industrial standards of UV-light stability for solar cells, and
      leading to the highest reported PCE of 14.03% for the inorganic
      perovskite/organic TSC.

PMID- 29633398
TI  - Role of bone scan index in the prognosis and effects of therapy on prostate
      cancer with bone metastasis: Study design and rationale for the multicenter
      Prostatic Cancer Registry of Standard Hormonal and Chemotherapy Using Bone Scan
      Index (PROSTAT-BSI) study.
AB  - OBJECTIVE: To present the study design and rationale of Prostatic Cancer Registry
      of Standard Hormonal and Chemotherapy Using Bone Scan Index, a prospective study
      aiming to determine the role of the bone scan index, the amount of bone
      metastasis, in the treatment and prognosis of prostate cancer patients. METHODS:
      A total of 237 patients were recruited at 30 hospitals in Japan. All had prostate
      cancer with bone metastasis and were scheduled to undergo either hormonal therapy
      (group H) or chemotherapy (group C). Bone scans were carried out with 99m Tc
      methylenediphosphonate. Follow-up studies are planned to continue for 3 years,
      and changes in biochemical and tumor markers in response to hormonal therapy and
      chemotherapy will be recorded in addition to skeletal-related events, recurrence,
      disease progression and death. RESULTS: The basic characteristics of the patients
      (n = 200) at the time of registration during December 2016 were as follows: mean
      age 71 +/- 8 years; median bone scan index calculated on-site 1.9% (range 0.02
      13.3%); median number of hot spots 18 (range 1-128); median prostate-specific
      antigen 155 ng/mL (range 0.04-22 412 ng/mL); and the most frequent Gleason score
      9 (47%). The prostate-specific antigen value was higher in group H than group C
      (288 vs 33 ng/mL, P < 0.0001), whereas bone scan indexes were comparable (1.7 vs
      2.3%, not significant) between the two groups. Liver metastasis was more frequent
      in group C than group H (6.1% vs 0.8%, P = 0.035). CONCLUSIONS: The baseline
      characteristics of the Prostatic Cancer Registry of Standard Hormonal and
      Chemotherapy Using Bone Scan Index database have been established. This
      collaborative study can now proceed with clarifying the role of the bone scan
      index for patient management including treatment strategies and prognosis.

PMID- 29633399
TI  - W-Based Atomic Laminates and Their 2D Derivative W1.33 C MXene with Vacancy
      Ordering.
AB  - Structural design on the atomic level can provide novel chemistries of hybrid MAX
      phases and their MXenes. Herein, density functional theory is used to predict
      phase stability of quaternary i-MAX phases with in-plane chemical order and a
      general chemistry (W2/3 M21/3 )2 AC, where M2 = Sc, Y (W), and A = Al, Si, Ga,
      Ge, In, and Sn. Of over 18 compositions probed, only two-with a monoclinic C2/c
      structure-are predicted to be stable: (W2/3 Sc1/3 )2 AlC and (W2/3 Y1/3 )2 AlC
      and indeed found to exist. Selectively etching the Al and Sc/Y atoms from these
      3D laminates results in W1.33 C-based MXene sheets with ordered metal
      divacancies. Using electrochemical experiments, this MXene is shown to be a new,
      promising catalyst for the hydrogen evolution reaction. The addition of yet one
      more element, W, to the stable of M elements known to form MAX phases, and the
      synthesis of a pure W-based MXene establishes that the etching of i-MAX phases is
      a fruitful path for creating new MXene chemistries that has hitherto been not
      possible, a fact that perforce increases the potential of tuning MXene properties
      for myriad applications.

PMID- 29633400
TI  - Elastic Self-Doping Organic Single Crystals Exhibiting Flexible Optical Waveguide
      and Amplified Spontaneous Emission.
AB  - Organic crystals are generally brittle and tend to crack under applied stress.
      Doped organic crystals are even more brittle because of lattice defects. Herein,
      the first doped organic crystals 1d@2d, which display elastic bending ability
      under applied stress, are reported. Moreover, the potential applications of
      elastic-doped crystals 1d@2d in flexible optoelectronics are impressively
      demonstrated. The elastic crystals 1d@2d with high quality and large size are
      crystalized by a simple and unique "self-doping" process, which is a regular
      solution evaporation of crude product 1d (2,5-dihydro-3,6
      bis(octylamino)terephthalate) containing a minute amount of 2d (3,6
      bis(octylamino)terephthalate) as the oxidized byproduct. The host 1d is easily
      crystallized to form elastic crystals but is nonfluorescent, while the guest 2d
      has poor crystallinity and is highly emissive. The doping approach integrates the
      advantages of both 1d and 2d, and thus endows doped crystals 1d@2d with good
      elasticity as well as intense orange fluorescence. Taking these advantages, the
      application potentials of these doped crystals 1d@2d are evaluated by measuring
      optical waveguide and amplified spontaneous emission in both the straight and
      bent states.

PMID- 29633401
TI  - Cerebellar and brainstem functional abnormalities in patients with primary
      orthostatic tremor.

PMID- 29633402
TI  - Comparing methods for detecting multilocus adaptation with multivariate genotype
      environment associations.
AB  - Identifying adaptive loci can provide insight into the mechanisms underlying
      local adaptation. Genotype-environment association (GEA) methods, which identify
      these loci based on correlations between genetic and environmental data, are
      particularly promising. Univariate methods have dominated GEA, despite the high
      dimensional nature of genotype and environment. Multivariate methods, which
      analyse many loci simultaneously, may be better suited to these data as they
      consider how sets of markers covary in response to environment. These methods may
      also be more effective at detecting adaptive processes that result in weak,
      multilocus signatures. Here, we evaluate four multivariate methods and five
      univariate and differentiation-based approaches, using published simulations of
      multilocus selection. We found that Random Forest performed poorly for GEA.
      Univariate GEAs performed better, but had low detection rates for loci under weak
      selection. Constrained ordinations, particularly redundancy analysis (RDA),
      showed a superior combination of low false-positive and high true-positive rates
      across all levels of selection. These results were robust across the demographic
      histories, sampling designs, sample sizes and weak population structure tested
      here. The value of combining detections from different methods was variable and
      depended on the study goals and knowledge of the drivers of selection. Re
      analysis of genomic data from grey wolves highlighted the unique, covarying sets
      of adaptive loci that could be identified using RDA. Although additional testing
      is needed, this study indicates that RDA is an effective means of detecting
      adaptation, including signatures of weak, multilocus selection, providing a
      powerful tool for investigating the genetic basis of local adaptation.

PMID- 29633403
TI  - Diagnosis of anaplastic large cell lymphoma on late peri-implant breast seroma:
      Management of cytological sample by an integrated approach.
AB  - INTRODUCTION: Peri-implant breast seroma is a late clinical presentation of
      reconstructive surgery or augmentation mammoplasty with breast implants. Pre
      operative cytological evaluation of the peri-implant breast seroma is a common
      clinical approach, showing mainly an inflammatory reaction or more rarely a
      breast implant-associated anaplastic large cell lymphoma. Herein, we reported the
      role of cytology in the evaluation of peri-implant breast seroma and its critical
      pre-operative implications. METHODS: Eight cases of peri-implant breast seroma
      from files at Luigi Vanvitelli University were identified between January and
      December 2017. In all cases, seroma was aspirated; cytospins were performed and
      stained by Papanicolaou stain; finally, in all cases, a cell block was obtained
      for immunocytochemical evaluation and, in one case, for FISH to detect ALK1-gene
      translocation. RESULTS: The median age of patients was 48 years and the mean time
      between the implant placement and the occurrence of peri-implant breast seroma
      was 18 months. Microscopic examination showed breast implant-associated
      anaplastic large cell lymphoma in one case, aspecific inflammatory reaction in
      six cases and silicon-associated reaction in one case. CONCLUSIONS: Peri-implant
      breast seroma may be caused by several pathological conditions with different
      clinical behaviour. A proper cytological approach to peri-implant breast seroma
      allows a correct differential diagnosis between inflammatory conditions and
      breast implant-associated anaplastic large cell lymphoma and an appropriate
      management of the patient.

PMID- 29633404
TI  - The centrality of the nurse-patient relationship: A Scandinavian perspective.
AB  - AIMS AND OBJECTIVES: To address aspects of importance in the nurse-patient
      relationship, as conceptualised within the Scandinavian healthcare context.
      BACKGROUND: An experiment in Beth Israel Hospital uncovered a set of core values
      (ontology) that were wiped away by stronger forces. Despite this, some of the
      ideas impacted the development of nursing thought and values in the Scandinavian
      countries, partly because they connected with deeper social values and also
      because investment was being put into explicitly identifying and understanding
      the core elements of nursing (ontology) and how to provide evidence that they
      found were important (epistemology). From that beginning and through the work of
      key thought leaders, Scandinavian nursing is ready to embark on a new phase,
      which could be helped by the Fundamentals of Care framework. DESIGN: This
      discursive position study offers insights from a public healthcare setting,
      influenced by values such as equal rights to equal care and/or cure. This study
      presents two complementing perspectives: an ontological and an epistemological,
      on establishing caring relationships. CONCLUSION: There are different pathways to
      follow in building person-oriented care; however, the nursing approach is both
      ontologically and epistemologically grounded and based on dialogue. RELEVANCE TO
      CLINICAL PRACTICE: Patients meet different nurses, the meeting may be short and,
      routine actions may be on the agenda. However, nurses must engage with patients'
      experiences and knowledge, in order to add to patients' present and future well
      being with their person-oriented care.

PMID- 29633405
TI  - delta13 C values in archaeological 14 C-AMS dated charcoals: assessing mid
      Holocene climate fluctuations and human response from a high-resolution isotope
      record (Arslantepe, Turkey).
AB  - RATIONALE: Past climate has always influenced human adaptation to the
      environment. In order to reconstruct palaeoclimate fluctuations and their role in
      the evolution of Near Eastern societies during the mid-Holocene, high-resolution
      Delta13 C records from fossil wood remains at the archaeological site of
      Arslantepe (eastern Turkey) have been developed. METHODS: After chemical
      treatment, delta13 C values were measured by sample combustion flow using a FLASH
      EA-CHNS instrument interfaced with a Delta V isotope ratio mass spectrometer via
      a CONFLO III. Two replicates per sample were analysed. The measurement precision
      was evaluated by propagating variations of the delta13 C values of samples and V
      PDB standards, whereas the accuracy was checked by a quality control sample. To
      account for changes in atmospheric CO2 , Delta13 C values were calculated. In
      addition, 14 C/12 C ratios were measured by means of ann AMS system (3 MV tandem
      accelerator). RESULTS: Mean Delta13 C curves of deciduous Quercus and Juniperus
      from archaeological levels between 4700 and 2000 BC (Arslantepe periods VIII-VI
      D) were produced, where the isotope values were ordered by the available RC ages.
      Interspecific variations of evergreen vs deciduous plants were postulated for the
      juniper Delta13 C values being higher than 30/00. The seasonal rainfall amount
      was recorded by the juniper remains, while the water table levels were obtained
      from the oak samples. CONCLUSIONS: The local climate experienced times of
      enhanced/reduced precipitation in concert with regional trends. Anomalies in the
      air mass circulation from the Mediterranean basin also produced oscillations of
      rainfall amount. In such a frame the Rapid Climate Change dry events had a
      consistent signature in the Arslantepe Delta13 C record, thus potentially
      contributing to social or organisational changes at the site.

PMID- 29633406
TI  - Fundamental care-the quest for evidence.

PMID- 29633407
TI  - Photoexposed skin, skin ageing, Bateman's purpura and local vitamin C deficiency.

PMID- 29633408
TI  - Experiences and informational needs on sexual health in people with epilepsy or
      multiple sclerosis: A focus group investigation.
AB  - AIMS AND OBJECTIVES: To explore experiences and informational needs regarding
      sexual health in men and women with epilepsy or multiple sclerosis. BACKGROUND:
      Sexual health and well-being are dependent on access to comprehensive information
      about sexuality and good-quality sexual health care in an environment that
      affirms and promotes sexual health. DESIGN: The study had a qualitative
      explorative design using focus group methodology and framework analysis to
      capture the patient perspective. METHODS: We strategically selected 26
      participants at a neurological clinic at a university hospital in Denmark and
      conducted four homogeneous focus group interviews: women with epilepsy (n = 8),
      men with epilepsy (n = 7), women with multiple sclerosis (n = 5) and men with
      multiple sclerosis (n = 6). We used the framework method for analysis and
      initially developed a matrix of disease versus gender before the authors
      triangulated their views and decided on the final themes. RESULTS: We identified
      four themes and nine subthemes. Our main findings included insights on the impact
      of ignorance regarding sexual rehabilitation, demonstrating the importance of
      information in patients with sexual dysfunction related to chronic neurologic
      disease. The study expanded our understanding of sexual activity in the
      unpredictable body of epilepsy and the progressively changing body of multiple
      sclerosis. The participants agreed that they would have taken a more constructive
      path to solve their sexual problems if they had been aware of common responses to
      their disease. CONCLUSIONS: Our study suggests that people with epilepsy or
      multiple sclerosis might be under-informed regarding the impact of their disease
      on their sexual health. We have shown how knowledge deficits put people at risk
      for symptoms of isolation, guilt, frustration and depression. Patient information
      is a modifiable factor that, if improved, might increase the quality of life for
      this group of patients. RELEVANCE TO CLINICAL PRACTICE: Implementation of
      improved patient information at the neurological clinic is recommended.

PMID- 29633409
TI  - Hierarchical decision-making balances current and future reproductive success.
AB  - Parental decisions in animals are often context-dependent and shaped by fitness
      trade-offs between parents and offspring. For example, the selection of breeding
      habitats can considerably impact the fitness of both offspring and parents, and
      therefore, parents should carefully weigh the costs and benefits of available
      options for their current and future reproductive success. Here, we show that
      resource-use preferences are shaped by a trade-off between parental effort and
      offspring safety in a tadpole-transporting frog. In a large-scale in situ
      experiment, we investigated decision strategies across an entire population of
      poison frogs that distribute their tadpoles across multiple water bodies. Pool
      use followed a dynamic and sequential selection process, and transportation
      became more efficient over time. Our results point to a complex suite of
      environmental variables that are considered during offspring deposition, which
      necessitates a highly dynamic and flexible decision-making process in tadpole
      transporting frogs.

PMID- 29633410
TI  - Genomewide signatures of selection in Epichloe reveal candidate genes for host
      specialization.
AB  - Host specialization is a key process in ecological divergence and speciation of
      plant-associated fungi. The underlying determinants of host specialization are
      generally poorly understood, especially in endophytes, which constitute one of
      the most abundant components of the plant microbiome. We addressed the genetic
      basis of host specialization in two sympatric subspecies of grass-endophytic
      fungi from the Epichloe typhina complex: subsp. typhina and clarkii. The life
      cycle of these fungi entails unrestricted dispersal of gametes and sexual
      reproduction before infection of a new host, implying that the host imposes a
      selective barrier on viability of the progeny. We aimed to detect genes under
      divergent selection between subspecies, experiencing restricted gene flow due to
      adaptation to different hosts. Using pooled whole-genome sequencing data, we
      combined FST and DXY population statistics in genome scans and detected 57
      outlier genes showing strong differentiation between the two subspecies.
      Genomewide analyses of nucleotide diversity (pi), Tajima's D and dN/dS ratios
      indicated that these genes have evolved under positive selection. Genes encoding
      secreted proteins were enriched among the genes showing evidence of positive
      selection, suggesting that molecular plant-fungus interactions are strong drivers
      of endophyte divergence. We focused on five genes encoding secreted proteins,
      which were further sequenced in 28 additional isolates collected across Europe to
      assess genetic variation in a larger sample size. Signature of positive selection
      in these isolates and putative identification of pathogenic function supports our
      findings that these genes represent strong candidates for host specialization
      determinants in Epichloe endophytes. Our results highlight the role of secreted
      proteins as key determinants of host specialization.

PMID- 29633411
TI  - Solid nuclei and liquid droplets: A parallel treatment for 3 phase systems.
AB  - For solid phase self assembly into crystals or large diameter polymers, the
      presence of a liquid-liquid demixing transition has been known to have an
      accelerating effect on the nucleation process. We present a novel approach to the
      description of accelerated nucleation in which the formation of solid phase
      aggregates and liquid-like aggregates compete as parallel pathways to formation
      of dense phases. The central idea is that the small aggregates that would
      ultimately form the liquid phase are sufficiently labile to sample the
      configurations that would form the solid, so that the growing cluster begins as a
      liquid, and switches into growth as a solid when the aggregates have equal free
      energies. This can accelerate the reaction even when the liquid-demixed state is
      thermodynamically unfavorable. The rate-limiting barrier is therefore the energy
      at which there is a transition between liquid and solid, and the effective
      nucleus size is then concentration independent, even though for both nucleated
      demixing and nucleated crystallization, the nucleus size does depend on
      concentration. These ideas can be expressed in a chemical potential formalism
      that has been successfully used in nucleation of sickle hemoglobin, but not to
      our knowledge previously employed in describing LLD processes. The method is
      illustrated by considering existing data on Lysozyme.

PMID- 29633412
TI  - Volumetric laser endomicroscopy interpretation and feature analysis in dysplastic
      Barrett's esophagus.
AB  - BACKGROUND AND AIM: Volumetric laser endomicroscopy (VLE) is used to identify
      Barrett's esophagus (BE) dysplasia. Selection of a dysplastic region of interest
      (ROI) can be challenging due to feature variability across a large amount of
      data. The degree of agreement among VLE users in selecting a ROI has not been
      studied. METHODS: High-definition videos that divided a VLE scan from 18 patients
      with biopsy-proven BE dysplasia into 1-cm segments were reviewed using a four
      quadrant grid superimposed for systematic interpretation. VLE scans were selected
      based on image quality and appropriate visualization of BE epithelium. Four
      experienced VLE users rated each quadrant as dysplastic or non-dysplastic. For
      quadrants rated as dysplastic, reviewers selected a single timeframe with
      representative features. A high-degree of agreement among reviewers was defined
      as >=75% agreement on the quadrant diagnosis and >=50% agreement on selected
      timeframe (+/-2 s). RESULTS: Thirty-one videos, each 32 s in length, comprising
      124 quadrants were reviewed. There was high-agreement among reviewers in 99 (80%)
      quadrants, of which 68 (69%) were rated as dysplastic. Compared with quadrants
      rated as non-dysplastic, ROIs of quadrants rated as dysplastic contained a higher
      number of epithelial glands (12.7 vs 1.2, P < 0.001) with atypical architecture
      (54 vs 1, P < 0.001). A statistically significant difference was observed between
      the signal intensity profiles of quadrants rated as dysplastic and quadrants
      rated as non-dysplastic (P = 0.004). CONCLUSION: This study highlights that
      experienced VLE users can identify ROIs with high-degree of agreement. Selected
      ROIs contained VLE features associated with BE dysplasia.

PMID- 29633413
TI  - MR lymphography for sentinel lymph node detection in patients with oral cavity
      cancer: Preliminary clinical study.
AB  - BACKGROUND: The purpose of this study was to evaluate the feasibility of MR
      lymphography with interstitial injection of a gadolinium-based contrast agent for
      identifying sentinel lymph nodes in patients with oral cavity cancer and
      clinically negative neck. METHODS: Pretreatment MR lymphography with a
      differential subsampling with cartesian ordering (DISCO) sequence was performed
      in 26 patients with resectable oral cavity cancer and clinically negative neck,
      after peritumoral injection of 1-mL diluted gadobutrol. The accuracy of sentinel
      lymph node identification by MR lymphography was assessed and compared with the
      final histopathological results. RESULTS: The MR lymphography consistently
      visualized the 44 sentinel lymph nodes in all 26 patients. In all but 1 patient
      with pathologically positive neck, assumed sentinel lymph nodes revealed
      metastatic involvement. CONCLUSION: Pretreatment MR lymphography is a safe and
      feasible imaging technique that can help clinicians identify sentinel lymph nodes
      with a high risk of occult metastases in patients with oral cavity cancer,
      enabling focused preoperative biopsy in these high-risk patients.

PMID- 29633414
TI  - Time-varying synchronous cell ensembles during consummatory periods correlate
      with variable numbers of place cell spikes.
AB  - Spike rates of a hippocampal place cell are not constant and vary even when an
      animal visits an identical place field with nearly identical behavior. As one
      potential neurophysiological source underlying place cell spiking variability, we
      focused on the temporally fluctuating activity states of neuronal ensembles.
      Spike patterns of hippocampal neurons were recorded from rats performing a linear
      track task. Within a single consummatory period, similar sets of neurons were
      more frequently recruited in synchronous firing events, whereas different
      synchronized firing patterns of neuronal populations tended to be identified in
      different consummatory periods. A linear regression analysis indicated that the
      time-varying activation patterns of neuronal populations during consummatory
      periods are correlated with the spike rates of a place cell within its place
      field during running. These findings suggest that place cell in-field spiking is
      not only triggered by static inputs that represent external environments but also
      strongly depends on the time-varying internal states of neuronal populations.

PMID- 29633415
TI  - A novel gene-family involved in spermatophore generation in the economically
      important salmon louse Lepeophtheirus salmonis.
AB  - The salmon louse (Lepeophtheirus salmonis) is an important parasite of Atlantic
      salmon (Salmo salar). It is widely spread in aquaculture facilities and leads to
      economic losses every year. As it has developed resistances against many common
      treatments, new control methods must be established. Here we characterize a novel
      gene family of the salmon louse, consisting of two genes, which has not been
      described in other species before. We analyzed temporal expression patterns of
      both genes, the localization of mRNA and protein. An RNAi mediated gene knockdown
      lead to information about the function of the protein. Overall, these two genes
      are expressed only in sperm ducts of male sea lice. The mucin-like proteins can
      additionally be found in the wall of spermatophores, which are responsible for
      sperm transfer to females. Knockdown showed that both genes are essential for
      successful fertilization of females. Overall, all results indicate that the two
      analyzed genes are necessary for reproduction in sea lice as they are essential
      for the formation of a wall surrounding the spermatophores, which is needed for
      fertilization. Therefore, we name them Mucin-like spermatophore wall protein 1 &
      2 (MLSWP1 & MLSWP2). Analysis of sequence data from other copepod species
      suggests that MLSWPs are present in many copepod species and may also play a
      similar role in reproduction in those species.

PMID- 29633416
TI  - Missed nursing care and its relationship with confidence in delegation among
      hospital nurses.
AB  - AIMS AND OBJECTIVES: To (i) identify the types and reasons for missed nursing
      care among Jordanian hospital nurses; (ii) identify predictors of missed nursing
      care based on study variables; and (iii) examine the relationship between nurses'
      confidence in delegation and missed nursing care. BACKGROUND: Missed nursing care
      is a global concern for nurses and nurse administrators. Investigating the
      relation between the confidence in delegation and missed nursing care might help
      in designing strategies that enable nurses to minimise missed care and enhance
      quality of services. METHODS: A correlational research design was used for this
      study. A convenience sample of 362 hospital nurses completed the missed nursing
      care survey, and confidence and intent to delegate scale. RESULTS: The results of
      the study revealed that ambulating and feeding patients on time, doing mouth care
      and attending interdisciplinary care conferences were the most frequent types of
      missed care. The mean score for missed nursing care was (2.78) on a scale from 1
      5. The most prevalent reasons for missed care were "labour resources, followed by
      material resources, and then communication". Around 45% of the variation in the
      perceived level of "missed nursing care" was explained by background variables
      and perceived reasons for missed nursing. However, the relationship between
      confidence in delegation and missed care was insignificant. CONCLUSION: The
      results of this study add to the body of international literature on most
      prevalent types and reasons for missed nursing care in a different cultural
      context. RELEVANCE TO CLINICAL PRACTICE: Highlighting most prevalent reasons for
      missed nursing care could help nurse administrators in designing responsive
      strategies to eliminate or reduces such reasons.

PMID- 29633417
TI  - Editor's note.

PMID- 29633418
TI  - Formation of Hierarchical Cu-Doped CoSe2 Microboxes via Sequential Ion Exchange
      for High-Performance Sodium-Ion Batteries.
AB  - Electrode materials based on electrochemical conversion reactions have received
      considerable interest for high capacity anodes of sodium-ion batteries. However,
      their practical application is greatly hindered by the poor rate capability and
      rapid capacity fading. Tuning the structure at nanoscale and increasing the
      conductivity of these anode materials are two effective strategies to address
      these issues. Herein, a two-step ion-exchange method is developed to synthesize
      hierarchical Cu-doped CoSe2 microboxes assembled by ultrathin nanosheets using Co
      Co Prussian blue analogue microcubes as the starting material. Benefitting from
      the structural and compositional advantages, these Cu-doped CoSe2 microboxes with
      improved conductivity exhibit enhanced sodium storage properties in terms of good
      rate capability and excellent cycling performance.

PMID- 29633419
TI  - Targeting Aged Astrocytes May Be a New Therapeutic Strategy in Parkinson's
      Disease.

PMID- 29633420
TI  - Dermatoporosis and vitamin C deficiency.

PMID- 29633421
TI  - The provision of nurse-led follow-up at Norwegian intensive care units.
AB  - AIMS AND OBJECTIVES: To describe the prevalence, content and administration of
      intensive care unit diaries and follow-up practices offered to patients and their
      families in Norway. BACKGROUND: Intensive care treatment has been associated with
      risks for new or increased health impairments affecting both patients and their
      families. These impairments have the potential of continuing beyond the acute
      phase of treatment. In parallel, preventive actions have gradually become an
      integrated part of critical care nursing, and in Norway, national recommendations
      for the use of intensive care unit diaries have been established. DESIGN AND
      METHODS: A survey was conducted in Norwegian intensive care units offering care
      for adult patients, using a questionnaire asking about the frequency,
      administration and content of the follow-up offered to patients, their relatives,
      as well as bereaved family members. RESULTS: Thirty-nine of 66 (59.1%) invited
      intensive care units answered the questionnaire. The majority (n = 33, 84.6%) of
      the responding units had follow-up routines. The provision of diaries was the
      most frequent follow-up activity (n = 24, 61.5%), and consultations postdischarge
      formed an integrated part of the diary practice. Consultations with bereaved were
      conducted in 21 (53.8%) of the intensive care units. About one quarter of the
      responding intensive care units had positions for follow-up nursing staff.
      CONCLUSION: Nurse-led follow-up after critical care was a common activity in
      Norwegian intensive care units, comprising diaries and consultations offered to
      patients and family members. The follow-up was mainly driven by bottom-up
      processes conducted by dedicated nurses motivated by the patients' and their
      families' situation and feedback. RELEVANCE TO CLINICAL PRACTICE: Adherence to
      recommendations, as well as the availability of defined positions for aftercare
      nurses or teams, may improve the implementation of follow-up practices and reduce
      suffering after discharge from Norwegian intensive care units.

PMID- 29633422
TI  - Catathrenia in Pitt-Hopkins syndrome associated with 18q interstitial deletion.

PMID- 29633423
TI  - MET amplification in endometrial cancers with clear-cell carcinoma components.
AB  - Endometrial clear-cell carcinoma (ECC) is relatively rare. The expression of
      diagnostic markers in this disease is similar to that of clear-cell carcinoma,
      but the molecular carcinogenic events and therapeutic targets are mostly unknown.
      MET gene amplification has been reported in various cancers, including ovarian
      clear-cell carcinomas; however, the MET gene status has not previously been
      examined in ECC. We performed real-time quantitative PCR (QPCR) and fluorescence
      in situ hybridization (FISH) to analyze the MET gene statuses of 12 ECC cases. We
      found MET amplifications in two cases (2/12; 16.7%) by both methods. Of the 12
      cases, 9 were pure clear-cell carcinomas, and 3 were mixed types that included
      mixes with endometrioid carcinomas in 2 cases, and the remaining case was a
      heterologous-type carcinosarcoma that primarily consisted of a clear-cell
      carcinoma component and a scarce chondrosarcoma component. Both of the MET
      amplification cases were mixed; one contained endometrioid features, and the
      other chondrosarcoma features. This is the first report to analyze the statuses
      of the MET gene in ECCs, and the two mixed cases exhibited amplifications that
      are shared with ovarian clear-cell carcinomas. Further studies with larger
      numbers of cases are necessary to reveal the relationship between ECC and MET
      amplification.

PMID- 29633425
TI  - Membranous Nephropathy With Light Chain Restricted Deposits.
AB  - The literature on Membranous nephropathy (MN) with monoclonal deposits on
      immunofluorescence (IF) and their outcome is very scarce. We report our
      experience of managing five patients with this clinical entity. Mean age of the
      patients was 33.2+/-6.55 years. The mean proteinuria, serum albumin and serum
      creatinine was 5.73+/-2.17 g/day, 2.86+/-0.51 g/dL and 1.34+/-1.19 mg/dL,
      respectively. None of the patients had a lymphoproliferative disorder. Only one
      patient had an elevated free light chain ratio. Four (80%) patients were M-type
      phospholipase A2 receptor (PLA2R) negative (tissue and serum), and 1 (20%) was
      PLA2R related. Three (60%) cases had monoclonal IgG3/k, one IgG3/lambda, whereas
      one patient with PLA2R positivity had an IgG3/IgG4k subtype. Two (67%) patients
      treated with cyclical cyclophosphamide and steroids (cCYC/GC) achieved complete
      remission and one patient (33%) with elevated baseline creatinine had a reduction
      in serum creatinine with persistent proteinuria at the end of 12th month of
      follow-up. One patient with PLA2R positive MN was treated with Rituximab and is
      in complete remission. The patient with an elevated free light chain at baseline
      was treated with Bortezomib/Thalidomide/Dexamethasone, had complete remission at
      12 months, however, had a progressive rise in creatinine over the next 40 months
      of follow-up. The current series though limited by numbers documents the efficacy
      of conventional therapies in non-malignant associated MN with monoclonal deposits
      on IF.

PMID- 29633424
TI  - Tbx2 is required for the suppression of mesendoderm during early Xenopus
      development.
AB  - BACKGROUND: T-box family proteins are DNA-binding transcriptional regulators that
      play crucial roles during germ layer formation in the early vertebrate embryo.
      Well-characterized members of this family, including the transcriptional
      activators Brachyury and VegT, are essential for the proper formation of mesoderm
      and endoderm, respectively. To date, T-box proteins have not been shown to play a
      role in the promotion of the third primary germ layer, ectoderm. RESULTS: Here,
      we report that the T-box factor Tbx2 is both sufficient and necessary for
      ectodermal differentiation in the frog Xenopus laevis. Tbx2 is expressed
      zygotically in the presumptive ectoderm, during blastula and gastrula stages.
      Ectopic expression of Tbx2 represses mesoderm and endoderm, while loss of Tbx2
      leads to inappropriate expression of mesoderm- and endoderm-specific genes in the
      region fated to give rise to ectoderm. Misexpression of Tbx2 also promotes neural
      tissue in animal cap explants, suggesting that Tbx2 plays a role in both the
      establishment of ectodermal fate and its dorsoventral patterning. CONCLUSIONS:
      Our studies demonstrate that Tbx2 functions as a transcriptional repressor during
      germ layer formation, and suggest that this activity is mediated in part through
      repression of target genes that are stimulated, in the mesendoderm, by
      transactivating T-box proteins. Taken together, our results point to a critical
      role for Tbx2 in limiting the potency of blastula-stage progenitor cells during
      vertebrate germ layer differentiation. Developmental Dynamics 247:903-913, 2018.
      (c) 2018 Wiley Periodicals, Inc.

PMID- 29633426
TI  - Calcium signals act through histone deacetylase to mediate pronephric kidney
      morphogenesis.
AB  - BACKGROUND: Autosomal dominant polycystic kidney disease is the most common
      monogenetic kidney disorder and is linked to mutations in PKD1 and PKD2. PKD2, a
      Ca2+ -conducting TRP channel enriched in ciliated cells and gated by
      extracellular signals, is necessary to activate the multifunctional Ca2+/
      calmodulin-dependent protein kinase type 2 (CaMK-II), enabling kidney
      morphogenesis and cilia stability. RESULTS: In this study, antisense morpholino
      oligonucleotides and pharmacological compounds were employed to investigate the
      roles of class II HDAC family members (HDAC 4, 5, and 6) in Zebrafish kidney
      development. While all three class II HDAC genes were expressed throughout the
      embryo during early development, HDAC5-morphant embryos exhibited anterior cysts
      and destabilized cloacal cilia, similar to PKD2 and CaMK-II morphants. In
      contrast, HDAC4-morphant embryos exhibited elongated cloacal cilia and lacked
      anterior kidney defects. Suppression of HDAC4 partially reversed the cilia
      shortening and anterior convolution defects caused by CaMK-II deficiency, whereas
      HDAC5 loss exacerbated these defects. EGFP-HDAC4, but not EGFP-HDAC5,
      translocated into the nucleus upon CaMK-II suppression in pronephric kidney
      cells. CONCLUSIONS: These results support a model by which activated CaMK-II
      sequesters HDAC4 in the cytosol to enable primary cilia formation and kidney
      morphogenesis. Developmental Dynamics 247:807-817, 2018. (c) 2018 Wiley
      Periodicals, Inc.

PMID- 29633427
TI  - Normal lung function, do we need to go further than ethnic differences? More
      questions than answers.

PMID- 29633428
TI  - Porous Microrod Arrays Constructed by Carbon-Confined NiCo@NiCoO2 Core@Shell
      Nanoparticles as Efficient Electrocatalysts for Oxygen Evolution.
AB  - The study of cost-efficient and high-performance electrocatalysts for oxygen
      evolution reaction (OER) has attracted much attention. Here, porous microrod
      arrays constructed by carbon-confined NiCo@NiCoO2 core@shell nanoparticles
      (NiCo@NiCoO2 /C PMRAs) are fabricated by the reductive carbonization of
      bimetallic (Ni, Co) metal-organic framework microrod arrays (denoted as NiCo-MOF
      MRAs) and subsequent controlled oxidative calcination. They successfully combine
      the desired merits including large specific surface areas, high conductivity, and
      multiple electrocatalytic active sites for OER. In addition, the oxygen vacancies
      in NiCo@NiCoO2 /C PMRAs significantly improve the conductivity of NiCoO2 and
      accelerate the kinetics of OER. The above advantages obviously enhance the
      electrocatalytic performance of NiCo@NiCoO2 /C PMRAs. The experimental results
      demonstrate that the NiCo@NiCoO2 /C PMRAs as electrocatalysts exhibit high
      catalytic activity, low overpotential, and high stability for OER in alkaline
      media. The strategy reported will open up a new route for the fabrication of
      porous bimetallic composite electrocatalysts derived from MOFs with controllable
      morphology for electrochemical energy conversion devices.

PMID- 29633429
TI  - Effect of nicotine and alpha-7 nicotinic modulators on visceral pain-induced
      conditioned place aversion in mice.
AB  - BACKGROUND: Preclinical assays of affective and sensorial aspects of nociception
      play a key role in research on both the neurobiology of pain and the development
      of novel analgesics. Therefore, we investigated the effects of nicotine and alpha
      7 nicotinic acetylcholine receptor (nAChR) modulators in the negative affective
      and sensory components of visceral pain in mice. METHODS AND RESULTS:
      Intraperitoneal acetic acid (AA) administration resulted in a robust stretching
      behaviour and conditioned place aversion (CPA) in mice. We observed a dose
      dependent reduction in AA-induced stretching and CPA by the nonselective nAChRs
      agonist nicotine. Mecamylamine, a nonselective nAChRs agonist, was able to block
      its effects; however, hexamethonium, a peripherally restricted nonselective
      nicotinic antagonist, was able to block nicotine's effect on stretching behaviour
      but not on CPA. In addition, systemic administration of alpha7 nAChR full
      agonists PHA543613 and PNU282987 was failed to block stretching and CPA behaviour
      induced by AA. However, the alpha7 nAChR-positive allosteric modulator PNU120596
      blocked AA-induced CPA in a dose-dependent manner without reducing stretching
      behaviours. CONCLUSIONS: Our data revealed that while nonselective nAChR
      activation induces antinociceptive properties on the sensorial and affective
      signs of visceral pain in mice, alpha7 nAChRS activation has no effect on these
      responses. In addition, nonselective nAChR activation-induced antinociceptive
      effect on stretching behaviour was mediated by central and peripheral mechanisms.
      However, the effect of nonselective nAChR activation on CPA was mediated
      centrally. Furthermore, our data suggest a pivotal role of allosteric modulation
      of alpha7 nAChRS in the negative affective, but not sensory, component of
      visceral pain. SIGNIFICANCE: The present results suggest that allosteric
      modulation of alpha7 nAChR may provide new strategies in affective aspects of
      nociception.

PMID- 29633430
TI  - Natural history of serum HBV-RNA in chronic HBV infection.
AB  - Virus-like particles encapsulating HBV-RNA represent a serum biomarker for
      assessing viral replication activity in clinical practice. However, baseline
      levels of serum HBV-RNA and their associations with viral replicative
      intermediates and liver disease in phases of chronic hepatitis B remain unknown.
      In this cross-sectional study, 102 patients were categorized into immune-tolerant
      (IT), HBeAg-positive immune active (HBeAg+IA), inactive carrier (IC) and HBeAg
      negative immune active (HBeAg-IA) phases. HBV-RNA in serum samples and in 66
      paired liver biopsies were quantified and correlated with serum ALT levels,
      histopathological scores and the levels of other viral replicative intermediates.
      Mean levels of serum HBV-RNA differed among phases, with the highest levels among
      IT (6.78 +/- 0.83 log10 copies mL-1 ) patients, followed by HBeAg+IA (5.73 +/-
      1.16 log10 copies mL-1 ), HBeAg-IA (4.52 +/- 1.25 log10 copies mL-1 ) and IC
      (2.96 +/- 0.40 log10 copies mL-1 ) patients. Serum HBV-RNA levels correlated with
      HBV DNA in all phases, although correlations with other viral replicative
      intermediates weakened or disappeared when cases were stratified into phases.
      Distinct compositions of viral products were found among phases: the ratio of
      HBsAg to serum HBV-RNA was highest in IC patients, while the ratio of serum HBV
      RNA to intrahepatic HBV-RNA and the ratio of intrahepatic HBV-DNA to intrahepatic
      HBV-RNA were significantly higher in IT patients. In conclusion, baseline levels
      of HBV-RNA and the composition of viral replicative intermediates differ
      significantly across the natural course of chronic HBV infection. These findings
      shed light on the nature of viral replication and pathogenesis of disease among
      different phases of chronic HBV infection.

PMID- 29633431
TI  - Clinical examination and non-invasive screening tests in the diagnosis of
      peripheral artery disease in people with diabetes-related foot ulceration.
AB  - AIM: Peripheral artery disease is common in people with diabetes-related foot
      ulceration and is a risk factor for amputation. The best method for the detection
      or exclusion of peripheral artery disease is unknown. This study investigated the
      utility of clinical examination and non-invasive bedside tests in screening for
      peripheral artery disease in diabetes-related foot ulceration. METHODS: Some 60
      people presenting with new-onset ulceration participated. Accuracy of pulses,
      ankle pressure, toe pressure, toe-brachial index (TBI), ankle-brachial pressure
      index (ABPI), pole test at ankle, transcutaneous oxygen pressure and distal
      tibial waveform on ultrasound were examined. The gold standard diagnostic test
      used was > 50% stenosis in any artery or monophasic flow distal to calcification
      in any ipsilateral vessel on duplex ultrasound. RESULTS: The negative and
      positive likelihood ratios of pedal pulse assessment (0.75, 1.38) and the other
      clinical assessment tools were poor. The negative and positive likelihood ratios
      of ABPI (0.53, 1.69), transcutaneous oxygen pressure (1.10, 0.81) and ankle
      pressure (0.67, 2.25) were unsatisfactory. The lowest negative likelihood ratios
      were for tibial waveform assessment (0.15) and TBI (0.24). The highest positive
      likelihood ratios were for toe pressure (17.55) and pole test at the ankle
      (10.29) but the negative likelihood ratios were poor at 0.56 and 0.74.
      CONCLUSIONS: Pulse assessment and ABPI have limited utility in the detection of
      peripheral artery disease in people with diabetes foot ulceration. TBI and distal
      tibial waveforms are useful for selecting those needing diagnostic testing.

PMID- 29633432
TI  - Medically unexplained dermatologic symptoms still a problem.

PMID- 29633433
TI  - Effects of hypoxia inducible factors on pluripotency in human iPS cells.
AB  - A hypoxic condition is known to contribute to pluripotency. In the present
      article, the effects of transcription factors were first assessed regarding the
      proliferation and differentiation of human induced pluripotent stem (iPS) cells
      under hypoxic conditions using cell morphology and real-time polymerase chain
      reaction (RT-PCR). Morphology evaluations and RT-PCR revealed that the colony
      formation was promoted and the expression of pluripotent markers was increased
      under hypoxic conditions. In addition, the function of hypoxia inducible factors
      (HIFs) in human iPS cells under hypoxic conditions was evaluated in relation to
      the morphology and the expression of pluripotency markers by siRNA and RT-PCR.
      The HIF-2alpha silencing group showed a reduction in the colony size of human iPS
      cells and a statistically significant reduction in the expression of
      undifferentiation markers compared to the control group. Furthermore, the
      expression of HIF-2alpha was decreased when signal transducer and activator of
      transcription 3 (STAT3) was suppressed by its inhibitor, Stattic or S31 201. The
      inhibition using Stattic did not produce colony formation. The expression of
      pluripotent markers was also decreased using Stattic or S31 201. This study
      indicates that the HIF-2alpha expression in human iPS cells was activated under
      hypoxic conditions, similarly to that in murine iPS cells, and that HIF-2alpha
      among HIFs is the most effective compound for maintaining the pluripotency of
      human iPS cells. Furthermore, the STAT3 signal pathway regulates the expression
      of HIF-2alpha.

PMID- 29633434
TI  - An in vitro evaluation of the influence of neonatal endotracheal tube diameter
      and length on the work of breathing.
AB  - BACKGROUND: Neonates, particularly premature babies, are often managed with
      endotracheal intubation and subsequent mechanical ventilation to maintain
      adequate pulmonary gas exchange. There is no consensus on the standard length of
      endotracheal tube. Although a short tube reduces resistance and respiratory dead
      space, it is believed to increase the risk of accidental extubation. There are
      not entirely coherent data regarding the effect of endotracheal tube length on
      work of breathing in infants. AIM: The aim of this study was to evaluate the
      impact of neonatal endotracheal tube diameter and length on the work of breathing
      using an infant in vitro lung model. METHOD: We assessed the work of breathing
      index and mechanical ventilation settings with various endotracheal tube
      diameters and lengths using the JTR100 in vitro infant lung model. The basic
      parameters of the model were breathing frequency of 20 per minutes, inspiratory
      expiratory ratio of 1:3, and positive end-expiratory pressure of 5 cmH2 O. In
      addition, the diaphragm driving pressure to maintain the set tidal volume was
      measured as the work of breathing index. The JTR100 was connected to the Babylog
      8000plus through the endotracheal tube. Finally, we monitored the peak
      inspiratory pressure generated during assist-control volume guarantee mode with a
      targeted tidal volume of 10-30 mL. RESULTS: The diaphragm driving pressure using
      a 2.0-mm inner diameter tube was twice as high as that using a 4.0-mm inner
      diameter tube. To maintain the targeted tidal volume, a shorter tube reduced both
      the diaphragm driving pressure and ventilator-generated peak inspiratory
      pressure. The difference in the generated peak inspiratory pressure between the
      shortest and longest tubes was 5 cmH2 O. CONCLUSION: In our infant lung model, a
      shorter tube resulted in a lower work of breathing and lower ventilator-generated
      peak inspiratory pressure.

PMID- 29633435
TI  - Calcifications in prostate cancer: An active phenomenon mediated by epithelial
      cells with osteoblast-phenotype.
AB  - The main aim of this study was to investigate putative correlation between the
      formation of prostate calcifications and the presence of cancer cells showing the
      ultrastructural and morphological aspects of osteoblasts. To this end, 40
      prostate biopsies of prostate cancer were enrolled and investigated from
      histological, immunohistochemical, and ultrastructural point of view. To the best
      of our knowledge, this is the first study to propose a new cell type related to
      the ectopic calcifications in prostate tissue, the prostate osteoblast-like cells
      (POLCs). Although our data require further investigations about the molecular
      mechanisms of both POLCs Cells generation and calcification formation, this study
      can open new and interesting prospective in the management of prostate cancer
      patients. In fact, if our data will be validated in large-cohort studies, the
      presence of POLCs Cells and/or prostate calcifications could become a poor
      negative prognostic marker for cancer occurrence due to the correlation between
      the presence of POLCs Cells and epithelial to mesenchymal transition phenomenon.

PMID- 29633437
TI  - Pyoderma gangrenosum: a clinical conundrum.

PMID- 29633436
TI  - A qualitative study of older adults' and family caregivers' perspectives
      regarding their preoperative care transitions.
AB  - AIMS AND OBJECTIVES: To explore how older patients with multiple chronic
      conditions and their family caregivers perceive their engagement and overall care
      experience throughout the preoperative phase of elective orthopaedic hip or knee
      joint replacement. BACKGROUND: Patient engagement is a critical component of care
      necessary for improving patient outcomes. Little is known about how older adults
      with multiple chronic conditions and their family caregivers engage in
      preoperative care transitions and the subsequent impact of this experience on
      postoperative health outcomes. DESIGN: Prospective qualitative descriptive design
      was used. METHODS: Semi-structured telephone interviews with a convenience sample
      of older adults coping with multiple chronic conditions and their family
      caregivers. Interviews were conducted prior to surgery and, again 21 days
      postsurgery, were audio-recorded and transcribed for qualitative content
      analysis. The Quality Health Outcomes Model was used to categorise study
      findings. RESULTS: Eleven patients and five family caregivers participated.
      Guided by the Quality Health Outcomes Model, four major themes were identified.
      (i) Older adults perceive that joint replacement is about quality of life. (ii)
      Standardised interventions often fail to address the unique needs of complex
      older adults. (iii) Family caregivers perceive they are the primary care
      coordinators. (iv) Postoperative outcomes and resource utilisation vary widely in
      complex older adults. CONCLUSION: Findings suggest that current preoperative care
      interventions are often not designed to effectively engage complex older patients
      and their family caregivers. Coordinated patient-centred preoperative care that
      reflects the needs and goals of complex older patients and their family
      caregivers may positively influence perioperative care transitions and outcomes
      beyond this episode of care. RELEVANCE TO CLINICAL PRACTICE: The current research
      documents the need for more in-depth knowledge about the relationship between
      older adults' and their family caregivers' engagement preoperatively and
      postoperative outcomes and resource utilisation.

PMID- 29633438
TI  - Electromyographic Responses Across Different Pulse-Widths of Sacral
      Neuromodulation in Sheep.
AB  - OBJECTIVES: In rodents, we reported that short pulse-width (PW) neuromodulation
      might provide more efficient therapy delivery than traditional 0.21 msec PW.
      Using fully implanted, commercialized systems in the sheep, the goal of this
      study was to characterize the relationship of electromyographic (EMG) responses
      of the external anal sphincter (EAS) to different PWs of sacral neuromodulation
      (SNM). MATERIALS AND METHODS: In seven sheep, InterStim(r) quadripolar tined
      leads were implanted adjacent to the S3 nerve root bilaterally to deliver SNM and
      two pairs of intramuscular leads were placed on either side of the EAS for EMG
      sensing. The EMG responses to SNM with different PWs were examined using variable
      intensities in both anesthetized and conscious conditions. RESULTS: The EMG
      responses from ipsilateral EAS (IEAS ) and contralateral EAS (CEAS ) were
      compared. The area under the curve of EMG responses from IEAS were significantly
      stronger than that from CEAS. The late component EMGs were more sensitive to
      nerve stimulation with a higher response amplitude in awake sheep. The response
      threshold-PW relationship from the IEAS as ascertained visually and with EMG in
      anesthetized and awake sheep were fitted with a monoexponential nonlinear
      regression; the resulting chronaxies were of 0.05 msec (n = 6), and 0.04 msec (n
      = 6), and 0.04 msec (n = 8), respectively. CONCLUSIONS: In both anesthetized and
      awake conditions, a similar motor response may be evoked in the EAS at PWs much
      shorter (0.04-0.05 msec) than the 0.21 msec typically used with SNM. Potential
      battery savings manifested by shorter PW would provide more efficient therapy
      delivery and increased longevity of the stimulator.

PMID- 29633439
TI  - Insights into the Crystallization and Structural Evolution of Glycine Dihydrate
      by In Situ Solid-State NMR Spectroscopy.
AB  - In situ solid-state NMR spectroscopy is exploited to monitor the structural
      evolution of a glycine/water glass phase formed on flash cooling an aqueous
      solution of glycine, with a range of modern solid-state NMR methods applied to
      elucidate structural properties of the solid phases present. The glycine/water
      glass is shown to crystallize into an intermediate phase, which then transforms
      to the beta polymorph of glycine. Our in situ NMR results fully corroborate the
      identity of the intermediate crystalline phase as glycine dihydrate, which was
      first proposed only very recently.

PMID- 29633440
TI  - Augmenter of liver regeneration: A key protein in liver regeneration and
      pathophysiology.
AB  - Liver is constantly exposed to pathogens, viruses, chemicals, and toxins, and
      several of them cause injury, leading to the loss of liver mass and sometimes
      resulting in cirrhosis and cancer. Under physiological conditions, liver can
      regenerate if the loss of cells is less than the proliferation of hepatocytes. If
      the loss is more than the proliferation, the radical treatment available is liver
      transplantation. Due to this reason, the search for an alternative therapeutic
      agent has been the focus of liver research. Liver regeneration is regulated by
      several growth factors; one of the key factors is augmenter of liver regeneration
      (ALR). Involvement of ALR has been reported in crucial processes such as
      oxidative phosphorylation, maintenance of mitochondria and mitochondrial
      biogenesis, and regulation of autophagy and cell proliferation. Augmenter of
      liver regeneration has been observed to be involved in liver regeneration by not
      only overcoming cell cycle inhibition but by maintaining the stem cell pool as
      well. These observations have created curiosity regarding the possible role of
      ALR in maintenance of liver health. Thus, this review brings a concise
      presentation of the work done in areas exploring the role of ALR in normal liver
      physiology and in liver health maintenance by fighting liver diseases, such as
      liver failure, non-alcoholic fatty liver disease/non-alcoholic steatohepatitis,
      viral infections, cirrhosis, and hepatocellular carcinoma.

PMID- 29633441
TI  - Artisanal cachaca and brewer's spent grain as sources of yeasts with promising
      biotechnological properties.
AB  - AIMS: This study aimed to characterize yeasts isolated from the environment of
      artisanal cachaca production and brewer's spent grain-bearing in mind their
      further application in bioprocesses. METHODS AND RESULTS: Cell morphology, growth
      and fermentative parameters, and karyotyping were employed for the selection and
      grouping of yeast strains. The results showed that from 134 yeast strains
      studied, 14.2% exhibited cells with snowflake morphology, which is not
      appropriate for bioethanol production. The fermentation in sugarcane syrup was
      carried out with 71 Saccharomyces cerevisiae, 19 Torulaspora delbrueckii, eight
      Wickerhamomyces anomalus, six Candida parapsilosis, five Pichia mashurica, three
      Candida intermedia, two Clavispora lusitaniae and one Candida aaseri. Among the
      most important ethanol-producing strains, T. delbrueckii LMQA BSG 7 and S.
      cerevisiae LMQA SNR 65 presented biomass yield, ethanol yield and productivity
      similar or higher than PE-2 and CAT-1 (bioethanol industrial strains).
      CONCLUSIONS: This study showed a high potential for industrial application of the
      strains LMQA SNR 65 (S. cerevisiae) and LMQA BSG 7 (T. delbrueckii). It was found
      that the use of the chromosomal profile is not adequate to qualify yeasts
      concerning their technological performance. SIGNIFICANCE AND IMPACT OF THE STUDY:
      This study reported yeasts isolated from uncommon sources that present
      significant characteristics for potential application in bioprocesses.

PMID- 29633442
TI  - Fluorine-Free Synthesis of High-Purity Ti3 C2 Tx (T=OH, O) via Alkali Treatment.
AB  - MXenes, 2D compounds generated from layered bulk materials, have attracted
      significant attention in energy-related fields. However, most syntheses involve
      HF, which is highly corrosive and harmful to lithium-ion battery and
      supercapacitor performance. Here an alkali-assisted hydrothermal method is used
      to prepare a MXene Ti3 C2 Tx (T=OH, O). This route is inspired from a Bayer
      process used in bauxite refining. The process is free of fluorine and yields
      multilayer Ti3 C2 Tx with ca. 92 wt % in purity (using 27.5 m NaOH, 270  degrees
      C). Without the F terminations, the resulting Ti3 C2 Tx film electrode (ca. 52
      MUm in thickness, ca. 1.63 g cm-3 in density) is 314 F g-1 via gravimetric
      capacitance at 2 mV s-1 in 1 m H2 SO4 . This surpasses (by ca. 214 %) that of the
      multilayer Ti3 C2 Tx prepared via HF treatments. This fluorine-free method also
      provides an alkali-etching strategy for exploring new MXenes for which the
      interlayer amphoteric/acidic atoms from the pristine MAX phase must be removed.

PMID- 29633443
TI  - Melt Electrospinning Writing of Highly Ordered Large Volume Scaffold
      Architectures.
AB  - The additive manufacturing of highly ordered, micrometer-scale scaffolds is at
      the forefront of tissue engineering and regenerative medicine research. The
      fabrication of scaffolds for the regeneration of larger tissue volumes, in
      particular, remains a major challenge. A technology at the convergence of
      additive manufacturing and electrospinning-melt electrospinning writing (MEW)-is
      also limited in thickness/volume due to the accumulation of excess charge from
      the deposited material repelling and hence, distorting scaffold architectures.
      The underlying physical principles are studied that constrain MEW of thick, large
      volume scaffolds. Through computational modeling, numerical values variable
      working distances are established respectively, which maintain the electrostatic
      force at a constant level during the printing process. Based on the computational
      simulations, three voltage profiles are applied to determine the maximum height
      (exceeding 7 mm) of a highly ordered large volume scaffold. These thick MEW
      scaffolds have fully interconnected pores and allow cells to migrate and
      proliferate. To the best of the authors knowledge, this is the first study to
      report that z-axis adjustment and increasing the voltage during the MEW process
      allows for the fabrication of high-volume scaffolds with uniform morphologies and
      fiber diameters.

PMID- 29633444
TI  - Catalytic Dinitrogen Reduction to Ammonia at a Triamidoamine-Titanium Complex.
AB  - Catalytic reduction of N2 to NH3 by a Ti complex has been achieved, thus now
      adding an early d-block metal to the small group of mid- and late-d-block metals
      (Mo, Fe, Ru, Os, Co) that catalytically produce NH3 by N2 reduction and
      protonolysis under homogeneous, abiological conditions. Reduction of [TiIV
      (TrenTMS )X] (X=Cl, 1A; I, 1B; TrenTMS =N(CH2 CH2 NSiMe3 )3 ) with KC8 affords
      [TiIII (TrenTMS )] (2). Addition of N2 affords [{(TrenTMS )TiIII }2 (MU-eta1
      :eta1 -N2 )] (3); further reduction with KC8 gives [{(TrenTMS )TiIV }2 (MU-eta1
      :eta1 :eta2 :eta2 -N2 K2 )] (4). Addition of benzo-15-crown-5 ether (B15C5) to 4
      affords [{(TrenTMS )TiIV }2 (MU-eta1 :eta1 -N2 )][K(B15C5)2 ]2 (5). Complexes 3-5
      treated under N2 with KC8 and [R3 PH][I], (the weakest H+ source yet used in N2
      reduction) produce up to 18 equiv of NH3 with only trace N2 H4 . When only acid
      is present, N2 H4 is the dominant product, suggesting successive protonation
      produces [{(TrenTMS )TiIV }2 (MU-eta1 :eta1 -N2 H4 )][I]2 , and that extruded N2
      H4 reacts further with [R3 PH][I]/KC8 to form NH3 .

PMID- 29633445
TI  - Cleavable Binary Dyads: Simplifying Data Extraction and Increasing Storage
      Density in Digital Polymers.
AB  - Digital polymers are uniform macromolecules that store monomer-based binary
      sequences. Molecularly stored information is usually extracted from the polymer
      by a tandem mass spectrometry (MS/MS) measurement, in which the coded chains are
      fragmented to reveal each bit (i.e. basic coded monomer unit) of the sequence.
      Here, we show that data-extraction can be greatly simplified by favoring the
      formation of MS/MS fragments containing two bits instead of one. In order to do
      so, digital poly(alkoxyamine phosphodiester)s, containing binary dyads in each
      repeat unit, were prepared by an orthogonal solid-phase approach involving
      successive phosphoramidite and radical-radical coupling steps. Three different
      sets of monomers were considered to build these polymers. In all cases, four
      coded building blocks-two hydroxy-nitroxides and two phosphoramidite monomers
      were required to build the dyads. Among the three studied monomer sets, one
      combination allowed synthesis of uniform sequence-coded polymers. The resulting
      polymers led to clear dyad-containing fragments in MS/MS and could therefore be
      efficiently decoded. Additionally, an algorithm was created to detect specific
      dyad fragments, thus enabling automated sequencing.

PMID- 29633446
TI  - A novel INS mutation in a family with maturity-onset diabetes of the young:
      Variable insulin secretion and putative mechanisms.
AB  - Insulin gene (INS) mutations cause a rare form of maturity-onset diabetes of the
      young (MODY), a heterogeneous group of autosomal dominant diabetes with at least
      14 confirmed causative genes. Here, we describe a family with MODY due to a novel
      INS mutation, detected using massively parallel sequencing (MPS). The proband
      presented aged 11 years with mild diabetic ketoacidosis. She was negative for IA2
      and GAD antibodies. She had a strong family history of diabetes affecting both
      her two siblings and her mother, none of whom had ketosis but who were considered
      to have type 1 diabetes and managed on insulin, and her maternal grandfather, who
      was managed for decades on sulfonylureas. Of note, her younger sister had insulin
      deficiency but an elevated fasting proinsulin:insulin ratio of 76% (ref 5%-30%).
      Sanger sequencing of HNF4A, HNF1A, and HNF1B in the proband was negative.
      Targeted MPS using a custom-designed amplicon panel sequenced on an Illumina
      MiSeq detected a heterozygous INS mutation c.277G>A (p.Glu93Lys). Sanger
      sequencing confirmed the variant segregated with diabetes within the family.
      Structural analysis of this variant suggested disruption of a critical hydrogen
      bond between insulin and the insulin receptor; however, the clinical picture in
      some individuals also suggested abnormal insulin processing and insulin
      deficiency. This family has a novel INS mutation and demonstrated variable
      insulin deficiency. MPS represents an efficient method of MODY diagnosis in
      families with rarer gene mutations.

PMID- 29633447
TI  - Two cases of large cell acanthoma successfully treated with photodynamic therapy.

PMID- 29633448
TI  - Secukinumab: A positive outcome in a patient with severe psoriasis and HBV-HCV co
      infection.

PMID- 29633449
TI  - Non-Heme Iron Catalysts for Olefin Epoxidation: Conformationally Rigid Aryl-Aryl
      Junction To Support Amine/Imine Multidentate Ligands.
AB  - Atom-transfer chemistry represents an important class of reactions catalyzed by
      metalloenzymes. As a functional mimic of non-heme iron enzymes that deliver
      oxygen atoms to olefins, we have designed monoiron complexes supported by new N
      donor chelates. These ligands take advantage of heme-like conformational rigidity
      of the pi-conjugated molecular backbone, and synthetic flexibility of tethering
      non-heme donor groups for additional steric and electronic control. Iron
      complexes generated in situ can be used to carry out catalytic epoxidation of a
      wide range of olefin substrates by using mCPBA as a terminal oxidant. The fate of
      initial iron-peracid adduct and the involvement of iron-oxo species in this
      process were investigated further by mechanistic probes and isotope exchange
      studies. Our findings suggest that anilidopyridyl-derived [N,N]-bidentate motif
      could serve as a versatile structural platform to build non-heme ligands for
      catalytic oxidation chemistry.

PMID- 29633450
TI  - Estimating the contribution of surfactant replacement therapy to the alveolar
      pool: An in vivo study based on 13 C natural abundance in rabbits.
AB  - Variation of the isotopic abundance of selected nutrients and molecules has been
      used for pharmacological and kinetics studies under the premise that the
      administered molecule has a different isotopic enrichment from the isotopic
      background of the recipient subject. The aim of this study is to test the
      feasibility of assessing the contribution of exogenous surfactant phospholipids
      to the endogenous alveolar pool in vivo after exogenous surfactant replacement
      therapy in rabbits. The study consisted in measuring the consistency of 13 C/12 C
      ratio of disaturated-phosphatidylcholine palmitate (DSPC-PA) in 7 lots of
      poractant alfa, produced over a year, and among bronchoalveolar lavages of 20
      rabbits fed with a standard chow. A pilot study was performed in a rabbit model
      of lavage-induced surfactant deficiency: 7 control rabbits and 4 treated with
      exogenous surfactant. The contribution of exogenous surfactant to the alveolar
      pool was assessed after intra-tracheal administration of 200 mg/kg of poractant
      alfa. The 13 C content of DSPC-PA was measured by isotope ratio mass
      spectrometry. The mean DSPC-PA 13 C/12 C ratio of the 7 lots of poractant alfa
      was -18.80/00 with a SD of 0.10/00 (range: -18.90/00; -18.60/00). The mean 13
      C/12 C ratio of surfactant DSPC recovered from the lung lavage of 20 rabbits was 
      28.8 +/- 1.20/00 (range: -31.70/00; -25.70/00). The contribution of exogenous
      surfactant to the total alveolar surfactant could be calculated in the treated
      rabbits, and it ranged from 83.9% to 89.6%. This pilot study describes a novel
      method to measure the contribution of the exogenous surfactant to the alveolar
      pool. This method is based on the natural variation of 13 C, and therefore it
      does not require the use of chemically synthetized tracers. This method could be
      useful in human research and especially in surfactant replacement studies in
      preterm infants.

PMID- 29633451
TI  - In Situ Monitoring of RAFT Polymerization by Tetraphenylethylene-Containing
      Agents with Aggregation-Induced Emission Characteristics.
AB  - A facile and efficient approach is demonstrated to visualize the polymerization
      in situ. A group of tetraphenylethylene (TPE)-containing dithiocarbamates were
      synthesized and screened as agents for reversible addition fragmentation chain
      transfer (RAFT) polymerizations. The spatial-temporal control characteristics of
      photochemistry enabled the RAFT polymerizations to be ON and OFF on demand under
      alternating visible light irradiation. The emission of TPE is sensitive to the
      local viscosity change owing to its aggregation-induced emission characteristic.
      Quantitative information could be easily acquired by the naked eye without
      destroying the reaction system. Furthermore, the versatility of such a technique
      was well demonstrated by 12 different polymerization systems. The present
      approach thus demonstrated a powerful platform for understanding the controlled
      living radical polymerization process.

PMID- 29633452
TI  - Research protocol: The initiation, design and establishment of the Global
      Angelman Syndrome Registry.
AB  - BACKGROUND: Angelman syndrome (AS) is a rare neurodevelopmental disorder
      affecting between 1 in 15 000 and 1 in 24 000 individuals. The condition results
      in severe developmental and expressive language delays, motor impairments and a
      unique behavioural phenotype consisting of excessive laughter, smiling and
      sociability. While many studies have contributed knowledge about the causes and
      natural history of the syndrome, large scale longitudinal studies are required to
      advance research and therapeutics for this rare syndrome. METHOD: This article
      describes the protocol for the Global Angelman Syndrome Registry, and some
      initial findings. Due to the rarity of AS and the variability in symptom
      presentation, the registry team will strive for complete case ascertainment.
      Parents and caregivers will submit data to the registry via a secure internet
      connection. The registry consists of 10 modules that cover patient demographics;
      developmental, diagnostic, medical and surgical history, behaviour and
      development, epilepsy, medications and interventions and sleep. RESULTS: Since
      its launch at https://angelmanregistry.info in September 2016, almost 470
      individuals with AS have been signed up to the registry worldwide: 59% are from
      North and South America, 23% are from Europe, 17% are from the Asia Pacific
      region and 1% are from the Middle East or Africa. The majority of registrants are
      children, with only 16% aged over 20 years. Most participants indicated a
      chromosome deletion (76%), with fewer participants indicating a mutation,
      uniparental disomy or imprinting defect (20%). CONCLUSION: Findings indicate a
      need to consider recruitment strategies that target caregivers of older children
      and adults, and parents and caregivers from non-English speaking backgrounds.

PMID- 29633453
TI  - Physiological and regulatory underpinnings of geographic variation in reptilian
      cold tolerance across a latitudinal cline.
AB  - Understanding the mechanisms that produce variation in thermal performance is a
      key component to investigating climatic effects on evolution and adaptation.
      However, disentangling the effects of local adaptation and phenotypic plasticity
      in shaping patterns of geographic variation in natural populations can prove
      challenging. Additionally, the physiological mechanisms that cause organismal
      dysfunction at extreme temperatures are still largely under debate. Using the
      green anole, Anolis carolinensis, we integrate measures of cold tolerance (CTmin
      ), standard metabolic rate, heart size, blood lactate concentration and RNAseq
      data from liver tissue to investigate geographic variation in cold tolerance and
      its underlying mechanisms along a latitudinal cline. We found significant effects
      of thermal acclimation and latitude of origin on variation in cold tolerance.
      Increased cold tolerance correlates with decreased rates of oxygen consumption
      and blood lactate concentration (a proxy for oxygen limitation), suggesting
      elevated performance is associated with improved oxygen economy during cold
      exposure. Consistent with these results, co-expression modules associated with
      blood lactate concentration are enriched for functions associated with blood
      circulation, coagulation and clotting. Expression of these modules correlates
      with thermal acclimation and latitude of origin. Our findings support the oxygen
      and capacity-limited thermal tolerance hypothesis as a potential contributor to
      variation in reptilian cold tolerance. Moreover, differences in gene expression
      suggest regulation of the blood coagulation cascade may play an important role in
      reptilian cold tolerance and may be the target of natural selection in
      populations inhabiting colder environments.

PMID- 29633454
TI  - Electrooxidative Rhodium-Catalyzed C-H/C-H Activation: Electricity as Oxidant for
      Cross-Dehydrogenative Alkenylation.
AB  - Rhodium(III) catalysis has enabled a plethora of oxidative C-H
      functionalizations, which predominantly employ stoichiometric amounts of toxic
      and/or expensive metal oxidants. In contrast, we herein describe the first
      electrochemical rhodium-catalyzed C-H activation that avoids hazardous chemical
      oxidants. Environmentally benign twofold C-H/C-H functionalizations were
      accomplished with weakly coordinating benzoic acids and benzamides, employing
      electricity as the terminal oxidant and generating H2 as the sole byproduct.

PMID- 29633456
TI  - Like-likes-Like: Cooperative Hydrogen Bonding Overcomes Coulomb Repulsion in
      Cationic Clusters with Net Charges up to Q=+6e.
AB  - Quantum chemical calculations have been employed to study kinetically stable
      cationic clusters, wherein the monovalent cations are trapped by hydrogen bonding
      despite strongly repulsive electrostatic forces. We calculated linear and cyclic
      clusters of the hydroxy-functionalized cation N-(3-hydroxypropyl) pyridinium,
      commonly used as cation in ionic liquids. The largest kinetically stable cluster
      was a cyclic hexamer that very much resembles the structural motifs of molecular
      clusters, as known for water and alcohols. Surprisingly, strong cooperative
      hydrogen bonds overcome electrostatic repulsion and result in cationic clusters
      with a high net charge up to Q=+6e. The structural, spectroscopic, and electronic
      signatures of the cationic and related molecular clusters of 3-phenyl-1-propanol
      could be correlated to NBO parameters, supporting the existence of "anti
      electrostatic" hydrogen bonds (AEHB), as recently suggested by Weinhold. We also
      showed that dispersion forces enhance the cationic cluster formation and
      compensate the electrostatic repulsion of one additional positive charge.

PMID- 29633457
TI  - Searching for the genetic footprint of ancient and recent hybridization.
AB  - Determining the long-term consequences of hybridization remains a central quest
      for evolutionary biologists. A particular challenge is to establish whether and
      to what extent widespread hybridization results in gene flow (introgression)
      between parental taxa. In this issue of Molecular Ecology, Jordan et al. ()
      search for evidence of gene flow between two closely related species of Geum
      (Rosaceae), which hybridize readily in contemporary populations and where hybrid
      swarms have been recorded for at least 200 years (Ruhsam, Hollingsworth, & Ennos,
      ). The authors find mixed evidence of ancient introgression when analysing
      allopatric populations. Intriguingly, when analysing populations of a region
      where the two species occur either mixed in the same population or in close
      proximity, and where hybrids are presently common, Jordan and colleagues find
      that the majority of randomly sampled individuals analysed (92/96) show no
      evidence of introgression (defined as individuals with admixture coefficients of
      <1%). The few individuals identified as hybrids are shown to likely be F1 or
      early-generation backcrosses, indicating that even in sympatric regions,
      hybridization does not penetrate beyond a few generations. Based on their
      findings, Geum seems to be an example of little to no introgression despite
      contemporary hybridization.

PMID- 29633458
TI  - Characterization of the 3Dimension optical, geometrical, and mechanical profiles
      of iPP fiber with necking deformation.
AB  - We present a method for evaluating the 3D refractive indices and 3D true stress
      and/or 3D true strain profiles of "isotactic polypropylene iPP" fibers during
      necking deformation. Observing the changes in geometrical shape during the
      deformation process is necessary to understand the mechanical performance of iPP
      fibers. 3D geometric shape profile and actual stress and strain profiles were
      measured for iPP fibers during the propagation of neck deformation. These
      measurements were performed with the aid of an in-situ opto- mechanical device to
      dynamically characterize different properties of fibers at different strain
      rates. A software image analysis program was used to calculate the 3D opto
      mechanical properties of iPP fibers. The obtained results show that the used
      dynamic stretching device can be easily used to monitor the deformation process
      with high accuracy. The effective stress and strain can be determined from the
      filaments profile. For illustration microinterferograms are given.

PMID- 29633455
TI  - Colonization of medical devices by staphylococci.
AB  - The use of medical devices in modern medicine is constantly increasing. Despite
      the multiple precautionary strategies that are being employed in hospitals, which
      include increased hygiene and sterilization measures, bacterial infections on
      these devices still happen frequently. Staphylococci are among the major causes
      of medical device infection. This is mostly due to the strong capacity of those
      bacteria to form device-associated biofilms, which provide resistance to chemical
      and physical treatments as well as attacks by the host's immune system. Biofilm
      development is a multistep process with specific factors participating in each
      step. It is tightly regulated to provide a balance between biofilm expansion and
      detachment. Detachment from a biofilm on a medical device can lead to severe
      systemic infection, such as bacteremia and sepsis. While our understanding of
      staphylococcal biofilm formation has increased significantly and staphylococcal
      biofilm formation on medical devices is among the best understood biofilm
      associated infections, the extensive effort put in preclinical studies with the
      goal to find novel therapies against staphylococcal device-associated infections
      has not yet resulted in efficient, applicable therapeutic options for that
      difficult-to-treat type of disease.

PMID- 29633459
TI  - Exploratory study on the relationship between smoking and other risk behaviours
      among young smokers.
AB  - AIMS AND OBJECTIVES: To explore the relationship between smoking and other risk
      behaviours among Chinese young people in Hong Kong. BACKGROUND: There is growing
      concern about coexisting risk behaviours in young smokers. Information about
      smoking and other risk behaviours is crucial for developing interventions to
      promote smoking abstinence and adoption of healthy lifestyles. The relationship
      between smoking and other risk behaviours among Chinese young people in Hong Kong
      has not been explored. DESIGN: This is a mixed-method retrospective population
      based study. METHODS: A retrospective population-based study was conducted with
      1,147 young smokers through Youth Quitline between November 2011-July 2016.
      Attitudes, behaviours and experiences related to smoking and risk behaviours
      among Chinese young smokers were examined in semi-structured qualitative
      interviews with 30 participants randomly selected from the retrospective
      population-based study. RESULTS: In total, 45.5% participants reported engaging
      in at least one other risk behaviour. The interviews revealed that drinking
      alcohol may have a significant impact on quitting smoking. In addition, smoking
      may be a gateway for more serious risk behaviours during adolescence. Low health
      awareness may explain the unhealthy lifestyles among young smokers. CONCLUSIONS:
      This study bridges a gap in existing literature by exploring relationships
      between smoking and other risk behaviours among young people in Hong Kong.
      RELEVANCE TO CLINICAL PRACTICE: Given the interrelationships between smoking and
      other risk behaviours, a holistic approach should be used to promote smoking
      cessation and healthy lifestyles among young smokers. If young smokers improve
      their health and quit smoking at the same time, their physical and mental
      development will benefit as a secondary outcome.

PMID- 29633460
TI  - Academic performance of third-year medical students learning in rural settings.
AB  - OBJECTIVE: Investigate the academic performance of medical students in rural and
      remote discipline rotations by rurality of placement. DESIGN: A retrospective
      cohort study. SETTING: Rural and remote clinical placement locations in
      Queensland, Australia. PARTICIPANTS: University of Queensland third-year medical
      students. MAIN OUTCOME MEASURES: In this study, student results for a range of
      assessments are the main outcome measures with rural area of student placement
      locations as categorised by the Australian Standard Geographical Classification -
      Remoteness Areas system the independent variable of interest. RESULTS: There was
      a significant effect of Australian Standard Geographical Classification -
      Remoteness Areas of placement on the health project, clinical case presentation,
      clinical participation assessment and overall grade, after controlling for the
      potential confounding impact of sex, age, students who attended the rural
      clinical school, cohort year, rotation during the year and type of health service
      where students were placed. No significant effect of rural placement level was
      identified for the written examination, poster or journal of achievement
      assessments. CONCLUSION: Medical students' academic achievement is associated
      with many factors, but this study shows that being placed in remote areas is one
      factor that either does not impede or can positively influence the learning and
      academic performance of medical students.

PMID- 29633461
TI  - Eosinophilia in the muscle layer of the esophagus and the urinary bladder in a
      Multiple System Atrophy patient with dysphagia and dysuria.
AB  - Multiple system atrophy (MSA) is a spinocerebellar degenerative disease
      characterized by cerebellar ataxia, parkinsonism, and autonomic failure. A 75
      year-old woman who had suffered from dysphagia and dysuria under a diagnosis of
      probable MSA with predominant cerebellar ataxia underwent autopsy. Eosinophilia
      was seen extensively in the muscle layer of the esophagus and urinary bladder.
      Eosinophilic infiltration to the esophagus was localized in the smooth muscle
      layer and could be considered as "eosinophilic esophageal myositis" identified in
      patients with nutcracker esophagus and jackhammer esophagus. Dense eosinophilia
      was present within the smooth muscle layer of the urinary bladder along with
      muscle fiber degeneration. We suspected a neuropathic etiology associated with
      MSA as the cause of the histological changes in the esophagus and urinary
      bladder; however, the possibility that some other disease might also have been
      responsible for the eosinophilic infiltration of the muscle layer cannot be
      denied. To our knowledge, this is the first report showing localized eosinophilia
      in the muscle layers of the esophagus and urinary bladder in the same patient.
      Although localized eosinophilia in visceral muscle has not been understood well,
      our case suggests the possibility that it is a feature of functional motility
      disorders and may have a neuropathic etiology.

PMID- 29633462
TI  - Calcium-Mobilizing Behaviors of Neutral Cyclic ADP-Ribose Mimics that Integrate
      Modifications to the Nucleobase, Northern Ribose and Pyrophosphate.
AB  - Cyclic adenosine diphosphate ribose (cADPR) is an endogenous Ca2+ mobilizer
      involved in diverse cellular processes. Mimics of cADPR play a crucial role in
      investigating the molecular mechanism(s) of cADPR-mediated signaling. Here,
      compound 3, a mimic of cADPR in which a neutral triazole moiety and an ether
      linkage were introduced to substitute the pyrophosphate and "northern" ribose
      components, respectively, was synthesized for the first time. The pharmacological
      activities in Jurkat cells indicated that this mimic is capable of penetrating
      plasma membrane and inciting Ca2+ release from the endoplasmic reticulum (ER)
      through the action of ryanodine receptors (RyRs) and triggering Ca2+ influx.
      Furthermore, a uridine moiety was introduced in place of adenine and the new
      cADPR mimics 4 and 5 were synthesized. The results of biological investigation
      showed that these mimics also targeted RyRs and retained moderate Ca2+ agonistic
      activities. The results indicated that the neutral cADPR mimics had the same
      targets for inducing Ca2+ signaling.

PMID- 29633463
TI  - Searching for a mathematical model for blood perfusion of random pattern skin
      flaps: a clinical pilot study using in vivo laser speckle contrast imaging.

PMID- 29633464
TI  - SUMOylation is required for fungal development and pathogenicity in the rice
      blast fungus Magnaporthe oryzae.
AB  - Amongst the various post-translational modifications (PTMs), SUMOylation is a
      conserved process of attachment of a small ubiquitin-related modifier (SUMO) to a
      protein substrate in eukaryotes. This process regulates many important biological
      mechanisms, including transcriptional regulation, protein stabilization, cell
      cycle, DNA repair and pathogenesis. However, the functional role of SUMOylation
      is not well understood in plant-pathogenic fungi, including the model fungal
      pathogen Magnaporthe oryzae. In this study, we elucidated the roles of four
      SUMOylation-associated genes that encode one SUMO protein (MoSMT3), two E1
      enzymes (MoAOS1 and MoUBA2) and one E2 enzyme (MoUBC9) in fungal development and
      pathogenicity. Western blot assays showed that SUMO modification was abolished in
      all deletion mutants. MoAOS1 and MoUBA2 were mainly localized in the nucleus,
      whereas MoSMT3 and MoUBC9 were localized in both the nucleus and cytoplasm.
      However, the four SUMOylation-associated proteins were predominantly localized in
      the nucleus under oxidative stress conditions. Deletion mutants for each of the
      four genes were viable, but showed significant defects in mycelial growth,
      conidiation, septum formation, conidial germination, appressorium formation and
      pathogenicity. Several proteins responsible for conidiation were predicted to be
      SUMOylated, suggesting that conidiation is controlled at the post-translational
      level by SUMOylation. In addition to infection-related development, SUMOylation
      also played important roles in resistance to nutrient starvation, DNA damage and
      oxidative stresses. Therefore, SUMOylation is required for infection-related
      fungal development, stress responses and pathogenicity in M. oryzae. This study
      provides new insights into the role of SUMOylation in the molecular mechanisms of
      pathogenesis of the rice blast fungus and other plant pathogens.

PMID- 29633465
TI  - Tuning of the Seebeck Coefficient and the Electrical and Thermal Conductivity of
      Hybrid Materials Based on Polypyrrole and Bismuth Nanowires.
AB  - The growing demand for clean energy catalyzes the development of new devices
      capable of generating electricity from renewable energy resources. One of the
      possible approaches focuses on the use of thermoelectric materials (TE), which
      may utilize waste heat, water, and solar thermal energy to generate electrical
      power. An improvement of the performance of such devices may be achieved through
      the development of composites made of an organic matrix filled with
      nanostructured thermoelectric materials working in a synergetic way. The first
      step towards such designs requires a better understanding of the fundamental
      interactions between available materials. In this paper, this matter is
      investigated and the questions regarding the change of electrical and thermal
      properties of nanocomposites based on low-conductive polypyrrole enriched with
      bismuth nanowires of well-defined geometry and morphology is answered. It is
      clearly demonstrated that the electrical conductivity and the Seebeck coefficient
      may be tuned either simultaneously or separately within particular Bi NWs content
      ranges, and that both parameters may be increased at the same time.

PMID- 29633466
TI  - Photoactivatable Adhesive Ligands for Light-Guided Neuronal Growth.
AB  - Neuro-regeneration after trauma requires growth and reconnection of neurons to
      reestablish information flow in particular directions across the damaged tissue.
      To support this process, biomaterials for nerve tissue regeneration need to
      provide spatial information to adhesion receptors on the cell membrane and to
      provide directionality to growing neurites. Here, photoactivatable adhesive
      peptides based on the CASIKVAVSADR laminin peptidomimetic are presented and
      applied to spatiotemporal control of neuronal growth to biomaterials in vitro.
      The introduction of a photoremovable group [6-nitroveratryl (NVOC), 3-(4,5
      dimethoxy-2-nitrophenyl)butan-2-yl (DMNPB), or 2,2'-((3'-(1-hydroxypropan-2-yl)
      4'-nitro-[1,1'-biphenyl]-4-yl)azanediyl)bis(ethan-1-ol) (HANBP)] at the amino
      terminal group of the K residue temporally inhibited the activity of the peptide.
      The bioactivity was regained through controlled light exposure. When used in
      neuronal culture substrates, the peptides allowed light-based control of the
      attachment and differentiation of neuronal cells. Site-selective irradiation
      activated adhesion and differentiation cues and guided seeded neurons to grow in
      predefined patterns. This is the first demonstration of ligand-based light
      controlled interaction between neuronal cells and biomaterials.

PMID- 29633468
TI  - Moving on....

PMID- 29633467
TI  - Defining extended half-life rFVIII-A critical review of the evidence.
AB  - INTRODUCTION: Recent haemophilia treatment advances include new recombinant FVIII
      (rFVIII) products with improved pharmacokinetic (PK) properties that aim to
      reduce the burden of prophylaxis. These treatments are commonly referred to as
      extended half-life rFVIII products (EHL rFVIII). There is no uniform definition
      of what constitutes an EHL rFVIII. Such a definition would help physicians,
      patients and funders understand the properties of standard and EHL rFVIIIs and
      thus provide clarity when selecting an EHL in clinical settings. AIM: To
      critically assess the published evidence on new and emerging rFVIII products in
      order to propose a definition to classify EHL rFVIIIs. METHODS: We systematically
      searched PubMed, EMBASE and regulatory authorities (FDA/EMA/Health Canada)
      websites for publications and regulatory submissions describing prospective
      crossover PK studies evaluating rFVIIIs that demonstrate improved PK parameters
      in adults and adolescents with severe haemophilia A. RESULTS: Following critical
      analyses of the published data, we developed a holistic approach to defining
      rFVIIIs as EHLs, which requires all of the following: (i) using technology
      designed to extend rFVIII half-life; (ii) lacking bioequivalence with a standard
      rFVIII comparator-above the FDA/EMA cut-off of 125% for the 90% confidence
      intervals for area under the curve ratio; and (iii) having an extended half-life
      ratio measured in a PK comparator crossover study. CONCLUSION: In this systematic
      review, a pragmatic definition of EHL rFVIII has been proposed that should
      provide better clarity in clinical discussions surrounding the appropriate use of
      rFVIII products. At present, only products using PEGylation or Fc fusion half
      life extension technology meet the proposed criteria for definition of EHL
      rFVIII.

PMID- 29633469
TI  - Sympatric serpentine endemic Monardella (Lamiaceae) species maintain habitat
      differences despite hybridization.
AB  - Ecological differentiation and genetic isolation are thought to be critical in
      facilitating coexistence between related species, but the relative importance of
      these phenomena and the interactions between them are not well understood. Here,
      we examine divergence in abiotic habitat affinity and the extent of hybridization
      and introgression between two rare species of Monardella (Lamiaceae) that are
      both restricted to the same serpentine soil exposure in California. Although
      broadly sympatric, they are found in microhabitats that differ consistently in
      soil chemistry, slope, rockiness and vegetation. We identify one active hybrid
      zone at a site with intermediate soil and above-ground characteristics, and we
      document admixture patterns indicative of extensive and asymmetric introgression
      from one species into the other. We find that genetic distance among
      heterospecific populations is related to geographic distance, such that the
      extent of apparent introgression is partly explained by the spatial proximity to
      the hybrid zone. Our work shows that plant species can maintain morphological and
      ecological integrity in the face of weak genetic isolation, intermediate habitats
      can facilitate the establishment of hybrids, and that the degree of apparent
      introgression a population experiences is related to its geographic location
      rather than its local habitat characteristics.

PMID- 29633470
TI  - Evaluation of changes in Bone Scan Index at different acquisition time-points in
      bone scintigraphy.
AB  - Bone Scan Index (BSI) is a validated imaging biomarker to objectively assess
      tumour burden in bone in patients with prostate cancer, and can be used to
      monitor treatment response. It is not known if BSI is significantly altered when
      images are acquired at a time difference of 1 h. The aim of this study was to
      investigate if automatic calculation of BSI is affected when images are acquired
      1 hour apart, after approximately 3 and 4 h. We prospectively studied patients
      with prostate cancer who were referred for bone scintigraphy according to
      clinical routine. The patients performed a whole-body bone scan at approximately
      3 h after injection of radiolabelled bisphosphonate and a second 1 h after the
      first. BSI values for each bone scintigraphy were obtained using EXINI boneBSI
      software. A total of 25 patients were included. Median BSI for the first
      acquisition was 0.05 (range 0-11.93) and for the second acquisition 0.21 (range 0
      13.06). There was a statistically significant increase in BSI at the second image
      acquisition compared to the first (P<0.001). In seven of 25 patients (28%) and in
      seven of 13 patients with BSI > 0 (54%), a clinically significant increase (>0.3)
      was observed. The time between injection and scanning should be fixed when
      changes in BSI are important, for example when monitoring therapeutic efficacy.

PMID- 29633472
TI  - 'Men just drink more than women. Women have friends to talk to'-Gendered
      understandings of depression among healthcare professionals and their
      implications.
AB  - Little is known about how gendered understandings of patients can inform
      professionals' discretionary actions and decisions to include or exclude in
      clinical practice. Using Connell's poststructuralist perspectives on gender as an
      analytic framework, this article aims to investigate how professionals'
      articulations of depression are framed by signs of masculinity and femininity,
      and how these articulations inform service provision to patients with depression
      in clinical psychiatry. Building on interview data drawn from an ethnographic
      study, the article shows how the professionals' articulations reflected a gender
      binary that framed how the feminized patients were often connected to psychiatric
      care while masculinized patients were referred to separate alcohol or substance
      use treatment outside the psychiatric institution. The article discusses the
      societal and institutional conditionality of gendered understandings in
      psychiatry. In spite of several limitations, the article elucidates how
      professionals' understandings might have wide-ranging implications for the
      accuracy of epidemiological research and policy, and how they reflect a power
      struggle between patients and professionals about the legitimate right to
      interpret patients' conditions and efforts to manage their illness-related
      problems.

PMID- 29633471
TI  - SUMO1-conjugation is altered during normal aging but not by increased amyloid
      burden.
AB  - A proper equilibrium of post-translational protein modifications is essential for
      normal cell physiology, and alteration in these processes is key in
      neurodegenerative disorders such as Alzheimer's disease. Recently, for instance,
      alteration in protein SUMOylation has been linked to amyloid pathology. In this
      work, we aimed to elucidate the role of protein SUMOylation during aging and
      increased amyloid burden in vivo using a His6 -HA-SUMO1 knock-in mouse in the
      5XFAD model of Alzheimer's disease. Interestingly, we did not observe any
      alteration in the levels of SUMO1-conjugation related to Alzheimer's disease.
      SUMO1 conjugates remained localized to neuronal nuclei upon increased amyloid
      burden and during aging and were not detected in amyloid plaques. Surprisingly
      however, we observed age-related alterations in global levels of SUMO1
      conjugation and at the level of individual substrates using quantitative
      proteomic analysis. The identified SUMO1 candidate substrates are dominantly
      nuclear proteins, mainly involved in RNA processing. Our findings open novel
      directions of research for studying a functional link between SUMOylation and its
      role in guarding nuclear functions during aging.

PMID- 29633473
TI  - Low serum creatinine predicts risk for type 2 diabetes.
AB  - AIMS: As an insulin target tissue, skeletal muscle is inversely related to type 2
      diabetes mellitus (T2DM). Serum creatinine originates mainly from creatine in
      muscle and is considered as a reliable surrogate marker for muscle mass in
      apparently healthy subjects. It is therefore hypothesized that low serum
      creatinine could effectively predict increased risk of T2DM. Yet information is
      scarce regarding the longitudinal relationship between serum creatinine and T2DM.
      This study aims to investigate this relation in a large general population of
      both men and women. METHODS: A prospective cohort study (n = 57 587; follow-up
      range: 1-9 years, mean: 3.57 years, 95% confidence interval: 3.55-3.58 years) was
      conducted in a general population sample from Tianjin, China. Multivariable Cox
      proportional hazards regression models were used to assess the relationship
      between baseline serum creatinine and the risk of developing T2DM (as defined by
      the American Diabetes Association criteria). RESULTS: During the follow-up
      period, 2017 subjects developed T2DM. The multivariate-adjusted hazard ratios
      (95% confidence interval) for T2DM incidence across quintiles of serum creatinine
      were 1.00 (reference), 0.86 (0.75, 0.99), 0.82 (0.72, 0.94), 0.85 (0.74, 0.97),
      and 0.77 (0.67, 0.89; P for trend <.01). Similar results were observed in both
      sexes (interaction P = .56). CONCLUSIONS: These findings indicate that serum
      creatinine concentration is inversely related to incident T2DM in both men and
      women. Measuring serum creatinine may assist in the early detection of
      individuals at high risk of developing T2DM.

PMID- 29633474
TI  - Creation of knowledge-based planning models intended for large scale
      distribution: Minimizing the effect of outlier plans.
AB  - Knowledge-based planning (KBP) can be used to estimate dose-volume histograms
      (DVHs) of organs at risk (OAR) using models. The task of model creation, however,
      can result in estimates with differing accuracy; particularly when outlier plans
      are not properly addressed. This work used RapidPlanTM to create models for the
      prostate and head and neck intended for large-scale distribution. Potential
      outlier plans were identified by means of regression analysis scatter plots,
      Cook's distance, coefficient of determination, and the chi-squared test. Outlier
      plans were identified as falling into three categories: geometric, dosimetric,
      and over-fitting outliers. The models were validated by comparing DVHs estimated
      by the model with those from a separate and independent set of clinical plans.
      The estimated DVHs were also used as optimization objectives during inverse
      planning. The analysis tools lead us to identify as many as 7 geometric, 8
      dosimetric, and 20 over-fitting outliers in the raw models. Geometric and over
      fitting outliers were removed while the dosimetric outliers were replaced after
      re-planning. Model validation was done by comparing the DVHs at 50%, 85%, and 99%
      of the maximum dose for each OAR (denoted as V50, V85, and V99) and agreed within
      -2% to 4% for the three metrics for the final prostate model. In terms of the
      head and neck model, the estimated DVHs agreed from -2.0% to 5.1% at V50, 0.1% to
      7.1% at V85, and 0.1% to 7.6% at V99. The process used to create these models
      improved the accuracy for the pharyngeal constrictor DVH estimation where one
      plan was originally over-estimated by more than twice. In conclusion, our results
      demonstrate that KBP models should be carefully created since their accuracy
      could be negatively affected by outlier plans. Outlier plans can be addressed by
      removing them from the model and re-planning.

PMID- 29633475
TI  - Socio-economic status and HbA1c in type 2 diabetes: A systematic review and meta
      analysis.
AB  - Up until now, differences in HbA1c levels by socio-economic status (SES) have
      been identified, but not yet quantified in people with type 2 diabetes. The aim
      of this study was therefore to assess the difference in HbA1c levels between
      people with type 2 diabetes of different SES in a systematic review and meta
      analysis. A systematic literature search was conducted in MEDLINE, Embase, Ebsco,
      and the Cochrane Library until January 14, 2018. Included studies described
      adults with type 2 diabetes in whom the association between SES and HbA1c levels
      was studied. Studies were rated for methodological quality and data were
      synthesized quantitatively (meta-analysis) and qualitatively (levels of
      evidence), stratified for type of SES variable, i.e., education, income,
      deprivation, and employment. Fifty-one studies were included: 15 high, 27
      moderate, and 9 of low methodological quality. Strong evidence was provided that
      people of low SES have higher HbA1c levels than people of high SES, for
      deprivation, education, and employment status. The pooled mean difference in
      HbA1c levels between people of low and high SES was 0.26% (95% CI, 0.09-0.43) or
      3.12 mmol/mol (95% CI, 1.21-5.04) for education and 0.20% (95% CI, -0.05 to 0.46)
      or 2.36 mmol/mol (95%CI, -0.61 to 5.33) for income. In conclusion, our systematic
      review and meta-analysis showed that there was an inverse association between SES
      and HbA1c levels in people with type 2 diabetes. Future research should focus on
      finding SES-sensitive strategies to reduce HbA1c levels in people with type 2
      diabetes.

PMID- 29633476
TI  - A framework for operationalizing risk: A practical approach to patient safety.
AB  - The importance of patient safety has grown tremendously; however, there are
      insufficient resources dedicated to its practical application. We provide an
      overview of the framework for addressing patient safety within the Johns Hopkins
      Health System, which approaches patient safety in the context of risk at the
      patient, provider, unit, and system levels. We present practical examples of how
      this approach is applied and highlight the resources needed as well as describe
      how it fits within the broader quality management infrastructure in the health
      system on its journey toward high reliability.

PMID- 29633477
TI  - Radiotherapy in the management of classic Kaposi's sarcoma: A single institution
      experience from Northeast Turkey.
AB  - Kaposi sarcoma is a rare adult neoplasm and there has been no certain consensus
      on standard treatment, either local or systemic. Radiotherapy is an effective,
      suitable treatment modality. Between 1996 and 2016, patients who were diagnosed
      with Kaposi sarcoma and referred to our clinic for radiotherapy were included in
      this retrospective study. Ninety-two patients were examined in total and it was
      diagnosed that all the patients had non-HIV associated Kaposi's sarcoma. There
      were 36 (39%) females and 56 (61%) males and female to male ratio was 2/3. Median
      age at presentation was 72 (30-93) years. Sixty-eight patients (77%) were treated
      with 8 Gy (1 fraction), 15 patients (16%) were treated with 20 Gy (2
      Gy/fraction), four patients (4%) were treated 25 Gy (2.5 Gy/fraction), and five
      patients (6%) were treated 30 Gy (3 Gy/fraction). The median follow-up time was
      72 (5-192) months. The complete response at 5 years was 91.6% with >20 Gy and
      89.6% with 8 Gy. Radiotherapy is an effective, suitable treatment modality of
      Classic Kaposi sarcoma and usually, radiotherapy is well tolerated with minimal
      side effects.

PMID- 29633478
TI  - "Auslander" (Foreigners), Migrants, or New Germans? Identity-Building Processes
      and School Socialization Among Adolescents From Immigrant Backgrounds in Germany.
AB  - In public discourse in Germany, identity is widely constructed along the
      juxtaposition of two categories: "German"-defined primordially in ethnic terms
      and "migrant" or "of migration background." But most urban schools today consist
      of a majority of children with such "non-German" backgrounds, while "ethnic
      German" children have become one minority among many others. Drawing from
      research on German identity, social mobility careers from among second-generation
      Turkey-originating families-including retrospective accounts of their school
      experiences in the 1960s to 2000s-and a very recent project on urban diversity,
      this article compares experiences of native-born adolescents and adults from
      immigrant families in relation to representations of Germanness. With immigrant
      children attending German schools over almost 50 years, it considers how
      demographic changes are shaping different experiences in the second and third
      generations and how this challenges German national self-definitions. The
      discussion examines meanings and effects on identity building and future
      orientations of youth from immigrant families and implications for future
      research in "majority-minority" societies.

PMID- 29633479
TI  - Future Orientation in Cultural Transition: Acculturation Strategies of Youth From
      Three Minority Groups in Israel.
AB  - Using adolescents' narratives and survey data presented in earlier studies, we
      draw upon Berry's model of four acculturation strategies () to examine
      adolescents' narratives regarding the future orientation domains of education-and
      career and marriage-and-family (Seginer, ) by three groups of nonimmigrant
      minority adolescents in Israel: Muslim, Druze, and ultra-Orthodox Jewish. The
      narratives of adolescents from the three communities studied here illustrate
      modified assimilation for education-and-career and separation for marriage-and
      family, indicating both cultural transition and continuity. Quantitative analyses
      mapped domain-specific links from education-and-career and marriage-and-family to
      adolescents' academic achievement.

PMID- 29633480
TI  - Therapeutic cannabinoids in multiple sclerosis: immunomodulation revisited.

PMID- 29633481
TI  - Osteosarcoma mimic in the breast: A recurrent malignant phyllodes tumour
      harbouring MED12 and hTERT mutations.

PMID- 29633482
TI  - Identification of novel mutations and risk assessment of Han Chinese patients
      with autosomal dominant polycystic kidney disease.
AB  - AIM: Autosomal dominant polycystic kidney disease (ADPKD) is the most common
      hereditary renal disease in humans and is caused by mutations in the PKD1 or PKD2
      gene. ADPKD is heterogeneous with regard to locus and allele heterogeneity and
      phenotypic variability. METHODS: Using targeted capture associated with next
      generation sequencing, we performed a mutational analysis of Han Chinese patients
      with ADPKD from 62 unrelated families. Multivariate Cox proportional hazard
      modeling of their different clinical characteristics and mutation classes was
      performed. RESULTS: The detection rate for a PKD1 and PKD2 mutation in the
      Chinese ADPKD patients was 95.2% (59/62). We identified pathogenic mutations in
      64.4% (38/59) of patients, including 32PKD1 mutations (15 nonsense mutations, 15
      frameshift mutation, one splice mutation, and one large deletion) and six PKD2
      mutations (three nonsense mutations and three frameshift mutations). Of the
      pathogenic variants we identified, 50% (19/38) were novel variants and 50%
      (19/38) were known variants. Patients with PKD2 mutations had milder and
      indistinguishable phenotypes. Significant phenotypic differences were observed
      among the various types of PKD1 mutations. CONCLUSION: Our results show that
      targeted capture associated with next-generation sequencing is an effective
      strategy for genetically testing ADPKD patients. This mutation analysis of ADPKD
      in Han Chinese extends our understanding of the genetic diversity of different
      ethnic groups, enriches the mutation database, and contributes to the genetic
      counselling of ADPKD patients.

PMID- 29633483
TI  - Versatile Three-Dimensional Porous Cu@Cu2 O Aerogel Networks as Electrocatalysts
      and Mimicking Peroxidases.
AB  - A facile strategy is presented to form 3D porous Cu@Cu2 O aerogel networks by
      self-assembling Cu@Cu2 O nanoparticles with the diameters of ca. 40 nm for
      constructing catalytic interfaces. Unexpectedly, the prepared Cu@Cu2 O aerogel
      networks display excellent electrocatalytic activity to glucose oxidation at a
      low onset potential of ca. 0.25 V. Moreover, the Cu@Cu2 O aerogels also can act
      as mimicking-enzymes including horseradish peroxidase and NADH peroxidase, and
      show obvious enzymatic catalytic activities to the oxidation of dopamine (DA), o
      phenyldiamine (OPD), 3,3,5,5-tetramethylbenzidine (TMB), and dihydronicotinamide
      adenine dinucleotide (NADH) in the presence of H2 O2 . These 3D Cu@Cu2 O aerogel
      networks are a new class of porous catalytic materials as mimic peroxidases and
      electrocatalysts and offer a novel platform to construct catalytic interfaces for
      promising applications in electrochemical sensors and artificial enzymatic
      catalytic systems.

PMID- 29633484
TI  - Cohort study to determine the waist circumference cutoffs for predicting type 2
      diabetes mellitus in rural China.
AB  - BACKGROUND: Limited information is available on the cutoffs of waist
      circumference (WC) for predicting type 2 diabetes mellitus (T2DM). We aimed to
      define the optimal WC cutoffs for predicting T2DM among rural Chinese people.
      METHODS: A cohort of 11 968 participants (732 new-onset T2DM) from a rural area
      in China with age 18 to 87 years was established at baseline during July to
      August of 2007 and 2008 and followed up during July to August of 2013 and 2014.
      Scatterplot, X-tile plot, and receiver operating characteristic (ROC) curve
      analyses were used to determine WC cutoffs for predicting T2DM. RESULTS: The WC
      cutoffs for males and females were 84 and 86 cm (scatterplot), 83 and 88 cm (X
      tile plot), and 87 and 88 cm (ROC curve). According to the highest risk score,
      the optimal WC cutoffs were 87 cm for males and 88 cm for females. With the
      optimal WC cutoffs, the sensitivity, specificity, positive likelihood ratio, area
      under the ROC curve, and population-attributable risk proportions were 67.9%,
      67.0%, 2.06%, 0.70%, and 46%, respectively, for males and 52.5%, 75.0%, 2.10%,
      0.69%, and 34%, respectively, for females; the corresponding adjusted hazard
      ratio for WC predicting T2DM was 3.66 (95% confidence interval 2.80-4.78) for
      males and 2.55 (2.08-3.12) for females. CONCLUSIONS: The optimal WC cutoffs for
      predicting T2DM were similar between males and females. As well, the criteria of
      WC for central obesity are no longer practical for predicting T2DM.

PMID- 29633485
TI  - Identity Development and Future Orientation in Immigrant Adolescents and Young
      Adults: A Narrative View of Cultural Transitions From Ethiopia to Israel.
AB  - This paper examines a major aspect of identity development in the context of
      cultural transition. Following Eriksonian psychosocial and sociocultural
      perspectives, it investigates self-continuity and identity integration in light
      of inherent discontinuity among young immigrants. More specifically, this
      examination draws on three distinct narrative studies, within the framework of
      Dynamic Narrative Approach, with first- and second-generation adolescents and
      young adult Ethiopian immigrants to Israel. Their negotiations of identity, with
      a focus on their narrative construction of past, present, and future across life
      domains (education, career, military service, family), are illustrated in this
      article in a variety of developmental paths. Dynamics of reciprocity between
      early life experiences and future orientation are revealed in the narratives. A
      capacity to connect cultural resources in the past with challenges in the new
      culture is identified as a key. By processing them and bringing them up-to-date,
      meaning becomes relevant to current experiences and developmental challenges.
      Across the three distinct studies, a variety of exploratory activities and
      relational qualities are found to facilitate or impede the reconstruction and
      integration of identity.

PMID- 29633487
TI  - Introduction: Navigating Pathways in Multicultural Nations: Identities, Future
      Orientation, Schooling, and Careers.

PMID- 29633486
TI  - Iridium-Catalyzed Annulation Reactions of Thiophenes with Carboxylic Acids:
      Direct Evidence for a Heck-type Pathway.
AB  - The functionalization of thiophenes is a fundamental and important reaction.
      Herein, we disclose iridium-catalyzed one-pot annulation reactions of
      (benzo)thiophenes with (hetero)aromatic or alpha,beta-unsaturated carboxylic
      acids, which afford thiophene-fused coumarin-type frameworks. Dearomatization
      reactions of 2-substituted thiophenes with alpha,beta-unsaturated carboxylic
      acids deliver various thiophene-containing spirocyclic products. The occurrence
      of two interconnected reactions provides direct evidence for a Heck-type pathway.
      The mechanistic scenario described herein is distinctly different from the SE Ar
      and concerted metalation-protodemetalation (CMD) pathways encountered in the well
      described oxidative C-H/C-H cross-coupling reactions of thiophenes with other
      heteroarenes.

PMID- 29633488
TI  - Nephrologists' perspectives on cancer screening in patients with chronic kidney
      disease: an interview study.
AB  - AIM: Patients with chronic kidney disease (CKD) have an increased risk of cancer
      compared with the general population. Despite this, there is considerable
      variability in cancer screening practices among nephrologists which may reflect
      uncertainties about the benefits and harms of screening, the additional costs,
      and competing priorities among the complex issues that patients are confronted
      with. We aimed to describe nephrologists' perspectives and approaches to cancer
      screening in CKD. METHODS: Semi-structured interviews were conducted with 29
      nephrologists from 15 units across Australia and New Zealand. Interviews were
      transcribed and thematically analyzed. RESULTS: Five themes were identified:
      empowering patients to make informed decisions (respecting patient preferences,
      communicating evidence-based recommendations, creating awareness of consequences,
      preparing for transplantation); justifiable risk taking (avoiding undue
      consequences in vulnerable populations, balancing the costs and benefits,
      warranted by long term immunosuppression, assurance of reasonable survival
      gains); ambiguity of evidence in supporting decisions (absence of standardized
      recommendations, limited transferability of population-based data); depending on
      a shared multidisciplinary approach (collaboration with primary health care,
      access to coordinated skin cancer clinics); and prioritizing current or imminent
      complications. CONCLUSION: Nephrologists approach decisions about cancer
      screening in patients with CKD based on patient preferences, assessment of risk,
      justifiable survival gains, and current health priorities. Evidence-based
      guidelines, communication frameworks and specialist clinics may support informed
      and shared decision making about cancer screening in CKD.

PMID- 29633490
TI  - Culture, Identity, Belonging, and School Success.

PMID- 29633489
TI  - Life stress and symptoms of anxiety and depression in women after cancer: The
      mediating effect of stress appraisal and coping.
AB  - OBJECTIVE: This paper examines the direct and intermediary relationships between
      life stress, stress appraisal, and resilience, and increased anxiety and
      depressive symptoms in Australian women after cancer treatment. METHODS: Data
      examined from 278 women aged 18 years and older previously treated for breast,
      gynaecological, or blood cancer, participating in the Australian Women's Wellness
      after Cancer Program. Serial mediation models interrogated the effect of
      stressful life events (List of Threatening Experiences-Modified) mediated by
      appraisal and coping (Perceived Stress Scale and Connor-Davidson Resilience
      Scale), on symptoms of anxiety and depression (Zung Self-rating Anxiety Scale and
      Center for Epidemiologic Studies Depression Scale). RESULTS: Over one-quarter
      (30.2%) of participants reported 1 or more stressful life events, other than
      their cancer, in the previous 6 months. Results indicate that perceived stress
      fully mediated the relationships between life stress, anxiety (indirect effect =
      0.09, Bias-corrected bootstrap 95% CI 0.02-0.18, Percent mediation = 0.51), and
      depressive symptoms (indirect effect = 0.11, Bias-corrected bootstrap 95% CI 0.02
      0.23, Percent mediation = 0.71) and accounted for more than half of the
      relationship between predictor and outcome. CONCLUSIONS: Findings indicate that
      stress appraisal mediated the relationship between past life stressors and
      anxiety and depressive symptoms. This analysis also highlights the need to
      consider wellness within a broader care context to identify potentially
      vulnerable patients to possibly avert future health concerns.

PMID- 29633491
TI  - Emerging therapeutic potential for xenin and related peptides in obesity and
      diabetes.
AB  - Xenin-25 is a 25-amino acid peptide hormone co-secreted from the same
      enteroendocrine K-cell as the incretin peptide glucose-dependent insulinotropic
      polypeptide. There is no known specific receptor for xenin-25, but studies
      suggest that at least some biological actions may be mediated through interaction
      with the neurotensin receptor. Original investigation into the physiological
      significance of xenin-25 focussed on effects related to gastrointestinal transit
      and satiety. However, xenin-25 has been demonstrated in pancreatic islets and
      recently shown to possess actions in relation to the regulation of insulin and
      glucagon secretion, as well as promoting beta-cell survival. Accordingly, the
      beneficial impact of xenin-25, and related analogues, has been assessed in animal
      models of diabetes-obesity. In addition, studies have demonstrated that
      metabolically active fragment peptides of xenin-25, particularly xenin-8, possess
      independent therapeutic promise for diabetes, as well as serving as bioactive
      components for the generation of multi-acting hybrid peptides with antidiabetic
      potential. This review focuses on continuing developments with xenin compounds in
      relation to new therapeutic approaches for diabetes-obesity.

PMID- 29633492
TI  - Mapping the Excited-State Potential Energy Surface of a Photomolecular Motor.
AB  - A detailed understanding of the operation and efficiency of unidirectional
      photomolecular rotary motors is essential for their effective exploitation in
      molecular nanomachines. Unidirectional motion relies on light-driven conversion
      from a stable (1 a) to a metastable (1 b) conformation, which then relaxes
      through a thermally driven helix inversion in the ground state. The excited-state
      surface has thus far only been experimentally characterised for 1 a. Here we
      probe the metastable, 1 b, excited state, utilising ultrafast transient
      absorption and femtosecond stimulated Raman spectroscopy. These reveal that the
      "dark" excited-state intermediate between 1 a and 1 b has a different lifetime
      and structure depending on the initial ground-state conformation excited. This
      suggests that the reaction coordinate connecting 1 a to 1 b differs to that for
      the reverse photochemical process. The result is contrasted with earlier
      calculations.

PMID- 29633493
TI  - Dynamic Nuclear Polarization NMR Spectroscopy of Polymeric Carbon Nitride
      Photocatalysts: Insights into Structural Defects and Reactivity.
AB  - Metal-free polymeric carbon nitrides (PCNs) are promising photocatalysts for
      solar hydrogen production, but their structure-photoactivity relationship remains
      elusive. Two PCNs were characterized by dynamic-nuclear-polarization-enhanced
      solid-state NMR spectroscopy, which circumvented the need for specific labeling
      with either 13 C- or 15 N-enriched precursors. Rapid 1D and 2D data acquisition
      was possible, providing insights into the structural contrasts between the PCNs.
      Compared to PCN_B with lower performance, PCN_P is a more porous and more active
      photocatalyst that is richer in terminal N-H bonds not associated with
      interpolymer chains. It is proposed that terminal N-H groups act as efficient
      carrier traps and reaction sites.

PMID- 29633494
TI  - Selective Conversion of CO2 into Isocyanate by Low-Coordinate Iron Complexes.
AB  - Discovery of the mechanisms for selective transformations of CO2 into organic
      compounds is a challenge. Herein, we describe the reaction of low-coordinate Fe
      silylamide complexes with CO2 to give trimethylsilyl isocyanate and the
      corresponding Fe siloxide complex. Kinetic studies show that this is a two-stage
      reaction, and the presence of a single equivalent of THF influences the rates of
      both steps. Isolation of a thermally unstable intermediate provides mechanistic
      insight that explains both the effect of THF in this reaction, and the way in
      which the reaction achieves high selectivity for isocyanate formation.

PMID- 29633495
TI  - Mechanisms of enhanced thrombin-generating capacity in patients with cirrhosis.

PMID- 29633496
TI  - Klinefelter syndrome as a risk factor for recurrent deep vein thrombosis in an
      adolescent male: Significance of a thorough physical examination.

PMID- 29633497
TI  - In Vitro Biosynthesis of the Nonproteinogenic Amino Acid Methoxyvinylglycine.
AB  - Oxyvinylglycines are a family of nonproteinogenic amino acids featuring an
      essential vinyl ether conferring mechanism-based inhibition of pyridoxal
      phosphate enzymes. The gene clusters for a few oxyvinylglycines are known, yet
      the biosynthetic origin of the vinyl ether is elusive. The in vitro biosynthesis
      of methoxyvinylglycine or l-2-amino-4-methoxy-trans-3-butenoic acid (AMB) is
      reported. It is shown that AMB is made from glutamate as an alanyl-AMB dipeptide
      and the rationale is provided for the N-term Ala. Using a chemical capture
      method, the order and timing of the modifications on non-ribosomal peptide
      synthetase (NRPS)-bound substrates was determined, including a cryptic
      hydroxylation of the Glu beta-carbon. Eliminating this hydroxy group likely
      generates a key alpha,beta-dehydroamino acid intermediate that facilitates
      decarboxylation. This work sheds light on vinyl ether biosynthesis and uncovers
      new NRPS chemistry.

PMID- 29633498
TI  - Cobalt Phosphide Composite Encapsulated within N,P-Doped Carbon Nanotubes for
      Synergistic Oxygen Evolution.
AB  - Exploring highly efficient and stable oxygen evolution reaction (OER)
      electrocatalysts such as transition-metal phosphides (TMPs) is critical to
      advancing renewable hydrogen fuel. TMP nanostructures typically involving binary
      or ternary TMPs tuned by cation or anion doping are suggested to be promising low
      cost and durable OER catalysts. Herein, the preparation of CoP/CoP2 composite
      nanoparticles encapsulated within N,P-doped carbon nanotubes (CoP/CoP2 @NPCNTs)
      is demonstrated as a synergistic electrocatalyst for OER via the calcination of a
      CoAl-layered double hydroxide/melamine mixture and subsequent phosphorization.
      Facile visualization by scanning electron microscopy in conjunction with electron
      backscatter diffraction demonstrates the encapsulation of the CoP/CoP2
      nanoparticles within the N,P-codoped CNTs. Electrocatalytic evaluation shows that
      the composite electrode requires a low overpotential of 300 mV for the OER at 10
      mA cm-2 in a 1.0 m KOH solution and, in particular, exhibits an excellent long
      term durability of ~100 h, which is superior to that of the state-of-the-art RuO2
      electrocatalyst. Density functional theory calculations reveal that the
      synergistic effect of CoP and CoP2 can enhance the electrocatalytic performance.
      In addition, molecular dynamics simulations demonstrate that the generated O2
      molecules can readily diffuse out of the CNTs. Both the effects give rise to the
      observed OER enhancement.

PMID- 29633499
TI  - Synthesis and Biological Evaluation of a Series of Novel Celastrol Derivatives
      with Amino Acid Chain.
AB  - The synthesis of celastrol analogues containing amino acid ester at the C(29)
      position and their evaluation for cytotoxic activities in vitro were reported.
      The MTT test showed that a set of derivatives with lower IC50 values than that of
      the positive control group cisplatin and the parent compound celastrol, which
      exhibited greater antiproliferative activities. The most potent title compounds
      2a and 2e exhibited cytotoxic activities in vitro against HeLa and A549 cell
      lines with IC50 values of 0.371 and 0.237 MUm, 0.235 and 0.109 MUm, respectively.
      The apoptosis assay demonstrated that 2a and 2e can induces of A549 cell
      apoptosis in low concentrations. These results showed that 2a and 2e may be
      promising for further research as antitumor agents.

PMID- 29633500
TI  - Interfacing Photosynthetic Membrane Protein with Mesoporous WO3 Photoelectrode
      for Solar Water Oxidation.
AB  - Photosynthetic biocatalysts are emerging as a new class of materials, with their
      sophisticated and intricate structure, which promise improved remarkable quantum
      efficiency compared to conventional inorganic materials in artificial
      photosynthesis. To break the limitation of efficiency, the construction of
      bioconjugated photo-electrochemical conversion devices has garnered substantial
      interest and stood at the frontier of the multidisciplinary research between
      biology and chemistry. Herein, a biohybrid photoanode of a photosynthetic
      membrane protein (Photosystem II (PS II)), extracted from fresh spinach entrapped
      on mesoporous WO3 film, is fabricated on fluorine-doped tin oxide. The PS II
      membrane proteins are observed to communicate with the WO3 electrode in the
      absence of any soluble redox mediators and sacrificial reagents under the visible
      light of the solar spectrum, even to 700 nm. The biohybrid electrode undergoes
      electron transfer and generates a significantly enhanced photocurrent compared to
      previously reported PS II-based photoanodes with carbon nanostructures or other
      semiconductor substrates for solar water oxidation. The maximum incident photon
      to-current conversion efficiency reaches 15.24% at 400 nm in the visible light
      region. This work provides some insights and possibilities into the efficient
      assembly of a future solar energy conversion system based on visible-light
      responsive semiconductors and photosynthetic proteins.

PMID- 29633501
TI  - Inferring the effect of genomic variation in the new era of genomics.
AB  - Accurate and detailed understanding of the effects of variants in the coding and
      noncoding regions of the genome is the next big challenge in the new genomic era
      of personalized medicine, especially to tackle newer findings of genetic and
      phenotypic heterogeneity of diseases. This is necessary to resolve the gene
      variant-disease relationship, the pathogenic variant spectrum of genes,
      pathogenic variants with variable clinical consequences, and multiloci diseases.
      In turn, this will facilitate patient recruitment for relevant clinical trials.
      In this review, we describe the trends in research at the intersection of basic
      and clinical genomics aiming to (a) overcome molecular diagnostic challenges and
      increase the clinical utility of next-generation sequencing (NGS) platforms, (b)
      elucidate variants associated with disease, (c) determine overall genomic
      complexity including epistasis, complex inheritance patterns such as "synergistic
      heterozygosity," digenic/multigenic inheritance, modifier effect, and rare
      variant load. We describe the newly emerging field of integrated functional
      genomics, in vivo or in vitro large-scale functional approaches, statistical
      bioinformatics algorithms that support NGS genomics data to interpret variants
      for timely clinical diagnostics and disease management. Thus, facilitating the
      discovery of new therapeutic or biomarker options, and their roles in the future
      of personalized medicine.

PMID- 29633502
TI  - Evidence for additionally increased apoptosis in the peripheral blood mononuclear
      cells of major depressive patients with a high risk for suicide.
AB  - Several studies have suggested a pathophysiological role of blood cell apoptosis
      in major depressive disorder (MDD). The aim of this study was to evaluate mRNA
      expression levels of Bcl-2, Bax, and Fas in peripheral blood mononuclear cells
      (PBMCs) of MDD patients with a high risk for suicide relative to those without a
      high risk for suicide as well as healthy subjects. The mRNA expression of Bcl-2,
      Bax, and Fas as well as the Bcl-2/Bax ratio was examined in the PBMCs of 30 MDD
      patients with a high risk for suicide, 30 MDD patients without a high risk for
      suicide, and 30 healthy controls. The mRNA expression of target genes was
      measured using real-time quantitative Polymerase Chain Reaction (PCR). FAS mRNA
      expression was significantly increased, and Bcl-2 mRNA expression and the Bcl
      2/Bax expression ratio were significantly decreased, in the PBMCs of MDD patients
      with or without a high risk for suicide attempts compared to healthy controls (p
      < .001). However, Bax mRNA expression was significantly increased only in MDD
      patients with a high risk for suicide. Moreover, MDD patients with a high risk
      for suicide had increased Bax and FAS mRNA expression and decreased Bcl-2 and Bcl
      2/Bax ratio when compared to patients without risk for suicide (p < .001). Our
      findings may support the role of both internal and external apoptotic pathways in
      the interplay between the immune system and depressive symptoms, especially in
      patients with a high risk for suicide.

PMID- 29633503
TI  - Level of empathy among dietitians: A pilot study.
AB  - AIM: The health-care providers' empathy has been linked to better patient
      outcomes. The increased demand for dietetics services has called for dietitians
      to examine their clinical practices and encounters with patients. To date, there
      are limited studies published on empathy among dietitians. Hence, this study
      aimed to determine the clinical dietitians' empathy level in Malaysia. METHODS:
      Using a purposive sampling method, this study was conducted on dietitians
      practising in the Malaysian hospitals (government and private). The Toronto
      Empathy Questionnaire (TEQ), a validated 16-item questionnaire was self
      administered, either by online survey method or face-to-face method. Additional
      information on gender, ethnicity, years of experience and percentage of working
      time spent on clinical, administrative and other areas were collected. RESULTS: A
      total of 69 dietitians participated in the study (private (n = 36) and government
      (n = 33)). The dietitians' mean total TEQ scores were 49.72 +/- 5.62 (score
      ranged between 35 and 63). Significant difference of mean total TEQ scores was
      found between dietitians from private (51.06 +/- 5.26) and government hospitals
      (48.27 +/- 5.72). There was no significant difference in the level of empathy by
      gender, ethnicity, years of experience and percentage of time spent on clinical
      consultations, administration or others while at work. CONCLUSIONS: Results from
      this study showed that there were differences in empathy level of Malaysian
      dietitians by work setting. This preliminary finding serves as a baseline for
      future studies and could facilitate the development of dietetics education in
      Malaysia.

PMID- 29633505
TI  - Gold-Catalyzed Regiospecific C-H Annulation of o-Ethynylbiaryls with Anthranils:
      pi-Extension by Ring-Expansion En Route to N-Doped PAHs.
AB  - We describe a novel, short, and flexible approach to diverse N-doped polycyclic
      aromatic hydrocarbons (PAHs) through gold-catalyzed pi-extension of anthranils
      with o-ethynylbiaryls as reagents. This strategy uses easily accessible starting
      materials, is simple due to high step and atom economy, and shows good functional
      group compatibility as well as scale-up potential. Mechanistically, the tandem
      reaction is proposed to involve a nucleophilic addition/ring
      opening/regiospecific C-H annulation/protodeauration sequence terminated by a
      Friedel-Crafts-type cyclization. Photophysical studies of the products indicated
      violet-blue fluorescence emission with quantum yields up to 0.45.

PMID- 29633504
TI  - FBXW7 deletion contributes to lung tumor development and confers resistance to
      gefitinib therapy.
AB  - Gefitinib, an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR
      TKI), is an effective treatment for non-small-cell lung cancer (NSCLC) with EGFR
      activating mutations, but inevitably, the clinical efficacy is impeded by the
      emergence of acquired resistance. The tumor suppressor gene FBXW7 modulates
      chemosensitivity in various human cancers. However, its role in EGFR-TKI therapy
      in NSCLC has not been well studied. Here, we demonstrate that the mice with
      deficient Fbxw7 have greater susceptibility to urethane-induced lung tumor
      development. Through analysis of The Cancer Genome Atlas data, we show that
      deletion of FBXW7 occurs in 30.9% of lung adenocarcinomas and 63.5% of lung
      squamous cell carcinomas, which significantly leads to decrease in FBXW7 mRNA
      expression. The reduction in FBXW7 mRNA level is associated with poor overall
      survival in lung cancer patients. FBXW7 knockdown dramatically promotes
      epithelial-mesenchymal transition, migration, and invasion in NSCLC cells.
      Moreover, with silenced FBXW7, EGFR-TKI-sensitive cells become resistant to
      gefitinib, which is reversed by the mammalian target of rapamycin inhibitor,
      rapamycin. Furthermore, xenograft mouse model studies show that FBXW7 knockdown
      enhances tumorigenesis and resistance to gefitinib. Combination of gefitinib with
      rapamycin treatment suppresses tumor formation of gefitinib-resistant (GR) FBXW7
      knockdown cells. In conclusion, our findings suggest that loss of FBXW7 promotes
      NSCLC progression as well as gefitinib resistance and combination of gefitinib
      and rapamycin may provide an effective therapy for GR NSCLC.

PMID- 29633506
TI  - Tumor necrosis factor-alpha -1031T/C polymorphism is associated with cognitive
      deficits in chronic schizophrenia patients versus healthy controls.
AB  - Recent compelling research has demonstrated a pathophysiologic role for
      proinflammatory cytokines of microglial origin in decreasing neurocognitive
      function. Psychiatric diseases are already known to have reduced cognitive
      function and are also associated with increased inflammation. To elaborate on
      these data, our study aims to investigate how a particular polymorphism of the
      tumor necrosis factor gene, TNF-alpha -1031T/C, affects neurocognitive
      performance in patients with schizophrenia. We recruited 905 patients with
      schizophrenia and 571 healthy control subjects. We employed the Repeatable
      Battery for the Assessment of Neuropsychological Status (RBANS) to test for
      neurocognitive function and the positive and negative syndrome scale to evaluate
      schizophrenia severity. The -1031T/C polymorphism was genotyped in both healthy
      controls and schizophrenic patients. Our results demonstrate that patients with
      the C allele (either T/C or C/C) possessed increased immediate memory index,
      visuospatial/constructional index, and RBANS total scores as compared to patients
      without it (p < .05). In healthy controls, there was no significant difference
      across genotypes (p > .05). Our findings demonstrate that the TNF-alpha -1031T/C
      polymorphism may not play a role in the susceptibility of schizophrenia itself,
      but may be involved in the cognitive deficits of schizophrenia. This suggests an
      important role for cytokine signaling in mediating the severity of cognitive
      dysfunction in schizophrenia.

PMID- 29633507
TI  - A randomised, placebo-controlled, multicentre, Phase 2 clinical trial to evaluate
      the efficacy and safety of GV1001 in patients with benign prostatic hyperplasia.
AB  - OBJECTIVES: To evaluate the efficacy and safety of three dosing schemes of GV1001
      in patients with benign prostatic hyperplasia (BPH). PATIENTS AND METHODS:
      Eligible patients were men aged >=50 years, with an International Prostate
      Symptom Score (IPSS) of >=13, maximum urinary flow rate (Qmax ) of 5-15 mL/s,
      post-void residual urine volume (PVR) of <=200 mL, and prostate volume of >=30
      mL. After a 4 week run-in period, patients were randomly assigned to one of three
      treatment schedules: Group 1, GV1001 0.4 mg, 2-week interval; Group 2, GV1001
      0.56 mg, 2-week interval; Group 3, GV1001 0.56 mg, 4-week interval) or placebo
      (Group 4). The eligible patients were administered GV1001 or placebo, for a total
      of seven intradermal injections that were administered at 2-week intervals at
      weeks 0, 2, 4, 6, 8, 10, and 12. Treatment continued for 12 weeks, and efficacy
      was evaluated at weeks 4, 8, 12, 13, and 16. Safety was evaluated throughout the
      16-week period. The primary efficacy variable was change from baseline (CFB) in
      total IPSS. Secondary endpoints were CFB in Qmax , PVR, prostate volume,
      International Index of Erectile Function score, plasma testosterone level,
      dihydrotestosterone level, and prostate-specific antigen level. RESULTS: A total
      of 161 patients were included (Group 1, n = 41; Groups 2-4, n = 40). Most
      patients (88.8%) received all planned doses of the study treatment. At week 13, a
      statistically significant difference in the mean CFB in IPSS was seen in GV1001
      treatment Groups 1 and 2 vs the control group for the full analysis population (
      3.5 [control] vs -7.2 and -6.8 in Groups 1 and 2, respectively; both P < 0.05).
      There were also statistically significant differences in CFB at weeks 8, 12, 13,
      and 16 in treatment Groups 1 and 2 vs control in the per-protocol population.
      There was a statistically significant reduction in prostate gland volume at week
      16 vs control in all treatment groups (0.8 [control] vs -4.6, -2.5, and -4.2 mL
      in Groups 1-3, respectively; all P < 0.05). There were no statistically
      significant differences found in other secondary outcome measures. Adverse event
      (AE) reporting was similar across all four groups. No treatment-emergent AEs were
      considered to be related to the study drug. CONCLUSIONS: The results indicate
      that GV1001 was effective and well tolerated, and may provide potential
      beneficial effects in patients with BPH. Compared with medical therapies that
      require daily dosing, the convenient dosing regimen of GV1001 may provide greater
      patient adherence. Further investigation of these observations will require large
      scale clinical evaluation.

PMID- 29633509
TI  - Mutation of a Nicotiana tabacum L. eukaryotic translation-initiation factor gene
      reduces susceptibility to a resistance-breaking strain of Potato virus Y.
AB  - Eukaryotic translation-initiation factors eIF4E and eIF(iso)4E in plants play key
      roles in infection by potyviruses and other plant RNA viruses. Mutations in the
      genes encoding these factors reduce susceptibility to the viruses, and are the
      basis of several recessive virus resistance genes widely used in plant breeding.
      Because virus variants occasionally break such resistance, the molecular basis
      for this process must be elucidated. Although deletion mutants of eIF4E1-S of
      tobacco (Nicotiana tabacum L.) resist Potato virus Y (PVY; the type member of the
      genus Potyvirus), resistance-breaking strains of PVY threaten tobacco production
      worldwide. Here, we used RNA interference technology to knock down tobacco eIF4E2
      S and eIF4E2-T genes or eIF(iso)4E-S and eIF(iso)4E-T genes. Transgenic plants
      with reduced transcript levels of both eIF(iso)4E-S and eIF(iso)4E-T showed
      reduced susceptibility to a resistance-breaking PVY strain with a K105E mutation
      in the viral genome-associated protein (VPg). By screening a population of
      chemically induced mutants of eIF(iso)4E-S and eIF(iso)4E-T, we showed that
      plants with a nonsense mutation in eIF(iso)4E-T, but not eIF(iso)4E-S, showed
      reduced susceptibility to the resistance-breaking PVY strain. In a yeast two
      hybrid assay, VPg of the resistance-breaking strain, but not wild-type PVY,
      physically interacted with the eIF(iso)4E-T protein. Thus, eIF4E1-S is required
      for infection by PVY, but eIF(iso)4E-T is required for infection by the
      resistance-breaking strain. Our study provides the first evidence for the
      involvement of a host eukaryotic translation-initiation factor in the infection
      cycle of a resistance-breaking virus strain. The eIF(iso)4E-T mutants will be
      useful in tobacco breeding to introduce resistance against resistance-breaking
      PVY strains.

PMID- 29633508
TI  - A canine in vitro model for evaluation of marrow-derived mesenchymal stromal cell
      based bone scaffolds.
AB  - Tissue engineered bone grafts based on bone marrow mesenchymal stromal cells
      (MSCs) are being actively developed for craniomaxillofacial (CMF) applications.
      As for all tissue engineered implants, the bone-regenerating capacity of these
      MSC-based grafts must first be evaluated in animal models prior to human trials.
      Canine models have traditionally resulted in improved clinical translation of CMF
      grafts relative to other animal models. However, the utility of canine CMF models
      for evaluating MSC-based bone grafts rests on canine MSCs (cMSCs) responding in a
      similar manner to scaffold-based stimuli as human MSCs (hMSCs). Herein, cMSC and
      hMSC responses to polyethylene glycol (PEG)-based scaffolds were therefore
      compared in the presence or absence of osteoinductive polydimethylsiloxane
      (PDMS). Notably, the conjugation of PDMS to PEG-based constructs resulted in
      increases in both cMSC and hMSC osteopontin and calcium deposition. Based on
      these results, cMSCs were further used to assess the efficacy of tethered bone
      morphogenic protein 2 (BMP2) in enhancing PEG-PDMS scaffold osteoinductivity.
      Addition of low doses of tethered BMP2 (100 ng/mL) to PEG-PDMS systems increased
      cMSC expression of osterix and osteopontin compared to both PEG-PDMS and PEG-BMP2
      controls. Furthermore, these increases were comparable to effects seen with up to
      five-times higher BMP2 doses noted in literature. (c) 2018 Wiley Periodicals,
      Inc. J Biomed Mater Res Part A: 106A:2382-2393, 2018.

PMID- 29633511
TI  - Optimization of PLGA formulation containing protein or peptide-based antigen:
      Recent advances.
AB  - Protein or peptide-based antigens are the most promising forms to generate custom
      protective immune responses for clinical applications. Over the last decades,
      poly(lactic-co-glycolic acid) (PLGA) as a biodegradable polymer has gained more
      attention for delivery of protein and peptide. Besides many appropriate
      characteristics, to improve its properties to overcome some obstacles such as
      release profile and it is important instability of antigen during both
      encapsulation and storage. Therefore, optimized procedures conditions require to
      be used to maintain the integrity of protein structure under several stress
      factors in formulation process. In this review article, the properties of PLGA
      particles, their preparation techniques and strategies for improvement of protein
      stability during encapsulation into PLGA, release from particle and storage as
      well as stabilization approaches were summarized. (c) 2018 Wiley Periodicals,
      Inc. J. Biomed. Mater. Res. Part A: 106A: 2540-2551, 2018.

PMID- 29633512
TI  - Mass coral bleaching causes biotic homogenization of reef fish assemblages.
AB  - Global climate change is altering community composition across many ecosystems
      due to nonrandom species turnover, typically characterized by the loss of
      specialist species and increasing similarity of biological communities across
      spatial scales. As anthropogenic disturbances continue to alter species
      composition globally, there is a growing need to identify how species responses
      influence the establishment of distinct assemblages, such that management actions
      may be appropriately assigned. Here, we use trait-based analyses to compare
      temporal changes in five complementary indices of reef fish assemblage structure
      among six taxonomically distinct coral reef habitats exposed to a system-wide
      thermal stress event. Our results revealed increased taxonomic and functional
      similarity of previously distinct reef fish assemblages following mass coral
      bleaching, with changes characterized by subtle, but significant, shifts toward
      predominance of small-bodied, algal-farming habitat generalists. Furthermore,
      while the taxonomic or functional richness of fish assemblages did not change
      across all habitats, an increase in functional originality indicated an overall
      loss of functional redundancy. We also found that prebleaching coral composition
      better predicted changes in fish assemblage structure than the magnitude of coral
      loss. These results emphasize how measures of alpha diversity can mask important
      changes in the structure and functioning of ecosystems as assemblages reorganize.
      Our findings also highlight the role of coral species composition in structuring
      communities and influencing the diversity of responses of reef fishes to
      disturbance. As new coral species configurations emerge, their desirability will
      hinge upon the composition of associated species and their capacity to maintain
      key ecological processes in spite of ongoing disturbances.

PMID- 29633510
TI  - Long noncoding RNA MALAT1 enhances the docetaxel resistance of prostate cancer
      cells via miR-145-5p-mediated regulation of AKAP12.
AB  - Our present work was aimed to study on the regulatory role of MALAT1/miR-145
      5p/AKAP12 axis on docetaxel (DTX) sensitivity of prostate cancer (PCa) cells. The
      microarray data (GSE33455) to identify differentially expressed lncRNAs and mRNAs
      in DTX-resistant PCa cell lines (DU-145-DTX and PC-3-DTX) was retrieved from the
      Gene Expression Omnibus (GEO) database. QRT-PCR analysis was performed to measure
      MALAT1 expression in DTX-sensitive and DTX-resistant tissues/cells. The human DTX
      resistant cell lines DU145-PTX and PC3-DTX were established as in vitro cell
      models, and the expression of MALAT1, miR-145-5p and AKAP12 was manipulated in
      DTX-sensitive and DTX-resistant cells. Cell viability was examined using MTT
      assay and colony formation methods. Cell apoptosis was assessed by TUNEL
      staining. Cell migration and invasion was determined by scratch test (wound
      healing) and Transwell assay, respectively. Dual-luciferase assay was applied to
      analyse the target relationship between lncRNA MALAT1 and miR-145-5p, as well as
      between miR-145-5p and AKAP12. Tumour xenograft study was undertaken to confirm
      the correlation of MALAT1/miR-145-5p/AKAP12 axis and DTX sensitivity of PCa cells
      in vivo. In this study, we firstly notified that the MALAT1 expression levels
      were up-regulated in clinical DTX-resistant PCa samples. Overexpressed MALAT1
      promoted cell proliferation, migration and invasion but decreased cell apoptosis
      rate of PCa cells in spite of DTX treatment. We identified miR-145-5p as a target
      of MALAT1. MiR-145-5p overexpression in PC3-DTX led to inhibited cell
      proliferation, migration and invasion as well as reduced chemoresistance to DTX,
      which was attenuated by MALAT1. Moreover, we determined that AKAP12 was a target
      of miR-145-5p, which significantly induced chemoresistance of PCa cells to DTX.
      Besides, it was proved that MALAT1 promoted tumour cell proliferation and
      enhanced DTX-chemoresistance in vivo. There was an lncRNA MALAT1/miR-145
      5p/AKAP12 axis involved in DTX resistance of PCa cells and provided a new thought
      for PCa therapy.

PMID- 29633514
TI  - Guideline of guidelines: primary monotherapies for localised or locally advanced
      prostate cancer.
AB  - Decisions regarding the primary treatment of prostate cancer depend on several
      patient- and disease-specific factors. Several international guidelines regarding
      the primary treatment of prostate cancer exist; however, they have not been
      formally compared. As guidelines often contradict each other, we aimed to
      systematically compare recommendations regarding the different primary treatment
      modalities of prostate cancer between guidelines. We searched Medline, the
      National Guidelines Clearinghouse, the library of the Guidelines International
      Network, and the websites of major urological associations for prostate cancer
      treatment guidelines. In total, 14 guidelines from 12 organisations were included
      in the present article. One of the main discrepancies concerned the definition of
      'localised' prostate cancer. Localised prostate cancer was defined as cT1-cT3 in
      most guidelines; however, this disease stage was defined in other guidelines as
      cT1-cT2, or as any T-stage as long as there is no lymph node involvement (N0) or
      metastases (M0). In addition, the risk stratification of localised cancer
      differed considerably between guidelines. Recommendations regarding radical
      prostatectomy and hormonal therapy were largely consistent between the
      guidelines. However, recommendations regarding active surveillance,
      brachytherapy, and external beam radiotherapy varied, mainly as a result of the
      inconsistencies in the risk stratification. The differences in year of
      publication and the methodology (i.e. consensus-based or evidence-based) for
      developing the guidelines might partly explain the differences in
      recommendations. It can be assumed that the observed variation in international
      clinical practice regarding the primary treatment of prostate cancer might be
      partly due to the inconsistent recommendations in different guidelines.

PMID- 29633513
TI  - ANP32E induces tumorigenesis of triple-negative breast cancer cells by
      upregulating E2F1.
AB  - Triple-negative breast cancer (TNBC) lacks expression of estrogen receptor (ER),
      progesterone receptor, and the HER2 receptor; it is highly proliferative and
      becomes the deadliest forms of breast cancer. Effective prognostic methods and
      therapeutic targets for TNBC are required to improve patient outcomes. Here, we
      report that acidic nuclear phosphoprotein 32 family member E (ANP32E), which
      promotes cell proliferation in mammalian development, is highly expressed in TNBC
      cells compared to other types of breast cancer. High expression of ANP32E
      correlates significantly with worse overall survival (OS; P < 0.001) and higher
      risks of disease recurrence (P < 0.001) in patients with TNBC. Univariate and
      multivariate Cox-regression models show that ANP32E is an independent prognostic
      factor in TNBC. Furthermore, we discovered that ANP32E promotes tumor
      proliferation in vitro by inducing G1/S transition, and ANP32E inhibition
      suppresses tumor formation in vivo. By examining the expression of E2F1, cyclin
      E1, and cyclin E2, we discovered that ANP32E promotes the G1/S transition by
      transcriptionally inducing E2F1. Taken together, our study shows that ANP32E is
      an efficient prognostic marker, and it promotes the G1/S transition and induces
      tumorigenesis of TNBC cells by transcriptionally inducing E2F1.

PMID- 29633515
TI  - Intermittent vs continuous docetaxel therapy in patients with metastatic
      castration-resistant prostate cancer - a phase III study (PRINCE).
AB  - OBJECTIVE: To investigate non-inferiority of intermittent docetaxel compared to
      continuous docetaxel in patients with metastatic castration-resistant prostate
      cancer (mCRPC). PATIENT AND METHODS: The investigator initiated randomised phase
      III study included 187 chemotherapy-naive patients with mCRPC who were allocated
      to two treatment arms: intermittent docetaxel and continuous docetaxel. Docetaxel
      was applied in both arms as weekly (35 mg/m2 ) or 3-weekly (75 mg/m2 ). The
      primary endpoint was 1-year survival, which was tested for non-inferiority
      (margin delta = 0.125). The secondary endpoints were: overall survival (OS),
      progression-free survival (PFS), median time to treatment failure (TTF), and
      toxicity. RESULTS: Of 156 eligible patients, 78 were allocated to each arm. The
      intermittent treatment met the non-inferiority criteria for 1-year survival (two
      sided 95% confidence interval, -0.12, 18, P = 0.022), but not for OS, according
      to the result of a post hoc analysis. The differences between the study arms in
      PFS and TTF were not significant. The median (range) treatment holiday in the
      intermittent arm was 110 (13-486) days, or 38% of the overall treatment duration.
      Safety profiles of both study arms were comparable. The main limitation of this
      study was that the planned number of patients could not be recruited. CONCLUSION:
      Intermittent docetaxel chemotherapy was non-inferior to continuous therapy for 1
      year survival; non-inferiority in regard to OS was not reached.

PMID- 29633516
TI  - Current concepts of the acontractile bladder.
AB  - The acontractile bladder (AcB) is a urodynamic-based diagnosis wherein the
      bladder is unable to demonstrate any contraction during a pressure flow study.
      Although it is often grouped with underactive bladder, it is a unique phenomenon
      and should be investigated independently. The purpose of the present review was
      to examine the current literature on AcB regarding its pathology, diagnosis,
      current management guidelines, and future developments. We performed a review of
      the PubMed database, classifying the evidence for AcB pathology, diagnosis,
      treatment, and potential future treatments. Over the 67 years covered in our
      review period, 42 studies were identified that met our criteria. Studies were
      largely poor quality and mainly consisted of retrospective review or animal
      models. The underlying pathology of AcB is variable with both neurological and
      myogenic aetiologies. Treatment is largely tailored for renal preservation and
      reduction of infection. Although future developments may allow more functional
      restorative treatments, current treatments mainly focus on bladder drainage. AcB
      is a unique and understudied bladder phenomenon. Treatment is largely based on
      symptoms and presentation. While cellular therapy and neuromodulation may hold
      promise, further research is needed into the underlying neuro-urological
      pathophysiology of this disease so that we may better develop future treatments.

PMID- 29633517
TI  - Platelet biology in regenerative medicine of skeletal muscle.
AB  - Platelet-based applications such as platelet-rich plasma (PRP) and platelet
      releasate have gained unprecedented attention in regenerative medicine across a
      variety of tissues as of late. The rationale behind utilizing PRP originates in
      the delivery of key cytokines and growth factors from alpha-granules to the
      targeted area, which in turn act as cell cycle regulators and promote the healing
      process across a variety of tissues. The aim of the present review is to
      assimilate current experimental evidence on the role of platelets as biomaterials
      in tissue regeneration, particularly in skeletal muscle, by integrating findings
      from human, animal and cell studies. This review is composed of 3 parts: firstly,
      we review key aspects of platelet biology that precede the preparation and use of
      platelet-related applications for tissue regeneration. Secondly, we critically
      discuss relevant evidence on platelet-mediated regeneration in skeletal muscle
      focusing on findings from (i) clinical trials, (ii) experimental animal studies
      and (iii) cell culture studies; and thirdly, we discuss the application of
      platelets in the regeneration of several other tissues including tendon, bone,
      liver, vessels and nerve. Finally, we review key technical variations in platelet
      preparation that may account for the large discrepancy in outcomes from different
      studies. This review provides an up-to-date reference tool for biomedical and
      clinical scientists involved in platelet-mediated tissue regenerative
      applications.

PMID- 29633518
TI  - Water deprivation decreases strength in fast twitch muscle in contrast to slow
      twitch muscle in rat.
AB  - AIM: The effects of dehydration on muscle performance in human are still
      contradictory, notably regarding muscle force. The effect of water deprivation
      (WD) on mechanical properties of skeletal muscle, and more precisely its impact
      on slow and fast muscles, remains largely unknown. The aim of this study was to
      determine for the first time whether WD leads to changes in contractile
      properties of skeletal muscle and whether these changes were muscle-type
      specific. METHODS: Sixteen-week-old male rats were assigned to either a control
      group (C) with water or a 96-hour WD group. At the end of the period, twitch and
      tetanus properties, as well as biochemical and structural analysis, were
      performed on soleus (SOL) and extensor digitorum longus (EDL) muscles. RESULTS:
      Absolute twitch (Pt) and tetanic (P0 ) tension were, respectively, 17% and 14%
      lower in EDL of WD rats as compared with C rats, whereas unexpected increases of
      43% and 25% were observed in SOL. Tensions normalized with respect to muscle mass
      were not affected by WD in EDL, whereas they were increased by more than 40% in
      SOL. A 96-hour WD period leads to a decrease in fibre cross-sectional area and
      absolute myofibrillar content only in EDL. CONCLUSION: It is hypothesized that
      differences in the results between slow and fast muscles may come from (i) a
      muscle-type-specific effect of WD on protein balance, EDL showing a greater
      myofibrillar protein breakdown and (ii) a greater sensitivity to osmolality
      changes induced by WD in EDL than in SOL.

PMID- 29633519
TI  - Genome-based evolutionary history of Pseudomonas spp.
AB  - Pseudomonas is a large and diverse genus of Gammaproteobacteria. To provide a
      framework for discovery of evolutionary and taxonomic relationships of these
      bacteria, we compared the genomes of type strains of 163 species and 3 additional
      subspecies of Pseudomonas, including 118 genomes sequenced herein. A maximum
      likelihood phylogeny of the 166 type strains based on protein sequences of 100
      single-copy orthologous genes revealed thirteen groups of Pseudomonas, composed
      of two to sixty three species each. Pairwise average nucleotide identities and
      alignment fractions were calculated for the data set of the 166 type strains and
      1224 genomes of Pseudomonas available in public databases. Results revealed that
      394 of the 1224 genomes were distinct from any type strain, suggesting that the
      type strains represent only a fraction of the genomic diversity of the genus. The
      core genome of Pseudomonas was determined to contain 794 genes conferring
      primarily housekeeping functions. The results of this study provide a
      phylogenetic framework for future studies aiming to resolve the classification
      and phylogenetic relationships, identify new gene functions and phenotypes, and
      explore the ecological and metabolic potential of the Pseudomonas spp.

PMID- 29633520
TI  - How far are we from viral hepatitis elimination service coverage targets?
AB  - INTRODUCTION: In 2016, the Global Health Sector Strategy (GHSS) on viral
      hepatitis called for elimination of viral hepatitis as a major public health
      threat by 2030 (i.e. 90% reduction in incidence and 65% in mortality). In 2017,
      WHO's first-ever Global Hepatitis Report presented the baseline values for each
      of the core indicators of the strategy. We review the challenges and
      opportunities that lie ahead in order to reach the 2030 service coverage targets.
      DISCUSSION: Three-dose coverage of hepatitis B vaccine in infancy reached 84% in
      2015 (2030 target: 90%); however, only 39% received the timely birth dose (2030
      target: 90%). Blood safety (97% of blood units screened with quality assurance,
      2030 target: 100%) and injection safety (5% unsafe injections, 2030 target: 0%)
      had made substantial progress while harm reduction fell short (27 syringe and
      needle sets distributed per person who injects drugs per year, 2030 target: 300).
      Worldwide, 9% and 20% of the HBV- and HCV-infected population respectively, were
      aware of their status (2030 targets: 90%). In the short term, to reach the 2020
      target of diagnosing 50% of those infected, 107 million HBV infected persons and
      15 million HCV infected persons should be urgently diagnosed. Overall, in 2015,
      less than 10% of known infected persons were on HBV treatment or had started HCV
      treatment (2030 targets: 80%). CONCLUSIONS: The prevention component of
      elimination is on track with respect to hepatitis B vaccination, blood safety,
      and injection safety. However, coverage of the hepatitis B vaccine timely birth
      dose requires a substantial increase, particularly in sub-Saharan Africa, and
      harm reduction needs to be taken to scale as injecting drug use accounts for a
      third of mortality from HCV infection. A promising but limited start in hepatitis
      testing and treatment needs to be followed by immediate and sustained action so
      that we reach the service coverage targets required to achieve elimination by
      2030. Treating persons coinfected with HIV and hepatitis viruses is particularly
      urgent and needs to be promoted in the context of the HIV response.

PMID- 29633521
TI  - The role of autophagy in age-related macular degeneration.

PMID- 29633522
TI  - Valuing Scholarship.

PMID- 29633523
TI  - Synthetic MUC1 Antitumor Vaccine with Incorporated 2,3-Sialyl-T Carbohydrate
      Antigen Inducing Strong Immune Responses with Isotype Specificity.
AB  - The endothelial glycoprotein MUC1 is known to underlie alterations in cancer by
      means of aberrant glycosylation accompanied by changes in morphology. The heavily
      shortened glycans induce a collapse of the peptide backbone and enable
      accessibility of the latter to immune cells, rendering it a tumor-associated
      antigen. Synthetic vaccines based on MUC1 tandem repeat motifs, comprising tumor
      associated 2,3-sialyl-T antigen, conjugated to the immunostimulating tetanus
      toxoid, are reported herein. Immunization with these vaccines in a simple
      water/oil emulsion produced a strong immune response in mice to which stimulation
      with complete Freund's adjuvant (CFA) was not superior. In both cases, high
      levels of IgG1 and IgG2a/b were induced in C57BL/6 mice. Additional glycosylation
      in the immunodominant PDTRP domain led to improved binding of the induced
      antisera to MCF-7 breast tumor cells, compared with that of the monoglycosylated
      peptide vaccine.

PMID- 29633524
TI  - Extracellular polysaccharide protects Rhizobium leguminosarum cells against zinc
      stress in vitro and during symbiosis with clover.
AB  - Rhizobium leguminosarum bv. trifolii is a soil bacterium that establishes
      symbiosis with clover (Trifolium spp.) under nitrogen-limited conditions. This
      microorganism produces exopolysaccharide (EPS), which plays an important role in
      symbiotic interactions with the host plant. The aim of the current study was to
      establish the role of EPS in the response of R. leguminosarum bv. trifolii cells,
      free-living and during symbiosis, to zinc stress. We show that EPS-deficient
      mutants were more sensitive to Zn2+ exposure than EPS-producing strains, and that
      EPS overexpression conferred some protection onto the strains beyond that
      observed in the wild type. Exposure of the bacteria to Zn2+ ions stimulated EPS
      and biofilm production, and increased cell hydrophobicity. However, zinc stress
      negatively affected the motility and attachment of bacteria to clover roots, as
      well as the symbiosis with the host plant. In the presence of Zn2+ ions, cell
      viability, root attachment, biofilm formation and symbiotic efficiency of EPS
      overproducing strains were significantly higher than those of the EPS-deficient
      mutants. We conclude that EPS plays an important role in the adaptation of
      rhizobia to zinc stress, in both the free-living stage and during symbiosis.

PMID- 29633525
TI  - What Develops in Cultural Transitions in Identities, Future Orientation, and
      School and Career Pathways?

PMID- 29633526
TI  - MicroRNAs as possible biomarkers for hepatocellular carcinoma.

PMID- 29633527
TI  - Potential of Krebs von den Lungen-6 as a predictor of relapse in interstitial
      pneumonia with anti-aminoacyl tRNA synthetase antibodies-positive
      dermatomyositis.
AB  - OBJECTIVE: To identify a predictor of relapse in interstitial pneumonia (IP) in
      patients with anti-aminoacyl tRNA synthetase antibodies-positive dermatomyositis
      (ARS-DMIP). METHODS: This retrospective cohort study comprised 27 ARS-DMIP
      patients. We compared clinical and laboratory findings between the relapse and
      non-relapse groups during 2 years after treatment initiation to find predictors
      of relapse in IP. Candidate predictors were further assessed by analysing the
      relationship with the relapse of IP. RESULTS: One patient with ARS-DMIP died.
      About 7 (26.9%) of the remaining 26 patients with ARS-DMIP had a relapse of IP.
      We found that the levels of serum Krebs von den Lungen-6 (KL-6) in the relapse
      group were significantly higher than those in the non-relapse group at the time
      points before treatment (P = .046) and after treatments, including 6 (P = .004),
      12 (P = .013), 18 (P = .003) and 24 months (P < .001). The KL-6 values that
      maximised the area under the ROC curve were 2347 U/mL before treatment, 622 U/mL
      after 6 months and 468 U/mL after 12 months. The relapse rates after 104 weeks
      were significantly higher in patients with KL-6 levels >=2400 U/mL before
      treatment (P = .014), >=600 ng/mL after 6 months (P < .005) and >=470 U/mL after
      12 months (P = .010). CONCLUSION: These findings suggest that the levels of KL-6
      before and after treatment in ARS-DMIP may represent the disease activity of IP,
      and they may be useful as the predictor of relapse in IP in patients with ARS
      DMIP.

PMID- 29633529
TI  - Understanding the epigenetic architecture of psychiatric disorders: Modifications
      and beyond.

PMID- 29633530
TI  - Poor prognosis of bladder cancer patients with occult lymph node metastases
      treated with neoadjuvant chemotherapy.
AB  - OBJECTIVES: To characterise the outcomes of neoadjuvant chemotherapy (NAC) pre
      treated patients found to be lymph node (LN)-positive at the time of radical
      cystectomy and pelvic lymph node dissection (RC/PLND) for urothelial carcinoma of
      the bladder (UCB). PATIENTS AND METHODS: Of 1484 patients treated with RC/PLND
      for UCB from 2000 to 2010, we analysed 198 patients with clinically non
      metastatic (cN0M0) muscle-invasive UCB who were found to be LN-positive at
      RC/PLND. As patients not receiving perioperative chemotherapy were significantly
      older and comorbid, we compared LN-positive patients previously treated with NAC
      (32 patients) to LN-positive patients treated with adjuvant chemotherapy (AC, 49
      patients) using Cox proportional hazards models. A sensitivity analysis was
      designed to account for the additional time to RC in NAC patients. RESULTS: The 3
      year recurrence-free survival estimate for LN-positive NAC patients was 26%,
      compared with 60% for LN-positive AC patients. LN-positive patients treated with
      NAC had significantly higher risks of disease recurrence and cancer-specific
      mortality in univariate analyses (hazard ratio [HR] 2.86, 95% confidence interval
      [CI] 1.58-5.19, P = 0.001 and HR 2.50, 95% CI 1.34-4.65, P = 0.004, respectively)
      and multivariable analyses adjusting for pathological stage and LN density (HR
      3.11, 95% CI 1.59-6.07, P = 0.001 and HR 3.05, 95% CI 1.46-6.35, P = 0.003,
      respectively). Sensitivity analyses similarly demonstrated worse outcomes for NAC
      pre-treated LN-positive patients. CONCLUSION: LN-positive patients previously
      treated with NAC have a poor prognosis, significantly worse than LN-positive
      patients subsequently treated with AC, and should be considered for protocols
      using sandwich chemotherapy approaches or novel agents. These results should be
      considered in the interpretation of and stratification for clinical trials.

PMID- 29633531
TI  - Efficient inference of paternity and sibship inference given known maternity via
      hierarchical clustering.
AB  - Pedigree and sibship reconstruction are important methods in quantifying
      relationships and fitness of individuals in natural populations. Current methods
      employ a Markov chain-based algorithm to explore plausible possible pedigrees
      iteratively. This provides accurate results, but is time-consuming. Here, we
      develop a method to infer sibship and paternity relationships from half-sibling
      arrays of known maternity using hierarchical clustering. Given 50 or more
      unlinked SNP markers and empirically derived error rates, the method performs as
      well as the widely used package Colony, but is faster by two orders of magnitude.
      Using simulations, we show that the method performs well across contrasting
      mating scenarios, even when samples are large. We then apply the method to open
      pollinated arrays of the snapdragon Antirrhinum majus and find evidence for a
      high degree of multiple mating. Although we focus on diploid SNP data, the method
      does not depend on marker type and as such has broad applications in nonmodel
      systems.

PMID- 29633532
TI  - Evaluation of home enteral nutrition services at public hospitals in New South
      Wales, Australia.
AB  - AIM: There is currently limited information regarding the home enteral nutrition
      population and its service practice at the state and national levels. The aim of
      this study is to report on patient numbers and demographics of the home enteral
      nutrition population in New South Wales, and to evaluate the implementation of
      home enteral nutrition services in public hospitals in the state. METHODS: A
      cross-sectional study was conducted using two online questionnaires, which were
      completed by the dietitian overseeing home enteral nutrition at each
      participating hospital. RESULTS: The home enteral nutrition population of
      participating hospitals was approximately 7600, with 81% oral nutrition support
      patients and 19% tube-fed patients. Mean compliance score to the home enteral
      nutrition implementation checklist was 54.1% (+/-20.7%), with a range of 14.3% to
      98.2%. Hospitals with a home enteral nutrition dietitian/coordinator scored a
      higher rate of compliance with the implementation checklist compared with
      hospitals without one (79.6% (+/-15.6%) vs 47.6% (+/-2.4%); P < 0.001). The key
      service improvements suggested by dietitians included increased funding towards a
      home enteral nutrition dietitian/coordinator (67.8%); improved resources to
      provide outpatient reviews, home visits and multidisciplinary service model
      (54.2%); improved database management and a more efficient registration process
      (52.5%). CONCLUSIONS: Home enteral nutrition services continue to be inconsistent
      across New South Wales. Funding and resource limitations were identified as the
      major barriers to addressing gaps in service provision.

PMID- 29633533
TI  - Association of mitochondrial displacement loop polymorphisms with diarrhea
      predominant irritable bowel syndrome: A preliminary study.
AB  - OBJECTIVES: To investigate whether single nucleotide polymorphisms (SNPs) in the
      mitochondrial displacement loop (D-loop) were associated with irritable bowel
      syndrome (IBS). METHODS: Altogether 40 participants were recruited and classified
      into three groups, including 20 that fulfilled the Rome III criteria for diarrhea
      predominant IBS (IBS-D), 10 with constipation-predominant IBS (IBS-C), and 10
      healthy volunteers (controls). DNA was extracted from biopsy specimens of the
      colon obtained during routine colonoscopies. The mitochondrial D-loop was
      sequenced and variants were identified in comparison with the reference sequence
      from GenBank. We searched GenBank and MITOMAP to determine whether a variant
      could be considered an SNP. RESULTS: No significant differences in sex, age and
      body mass index were found among the three groups. The average numbers of SNPs in
      the IBS-D, IBS-C and control groups were 12.2 +/- 2.7, 9.8 +/- 1.8 and 9.9 +/-
      2.1, respectively. The frequency of SNPs was significantly higher in the IBS-D
      group than in the IBS-C group and controls (P < 0.05). No significant difference
      was found between the latter two groups. Each SNP was compared among the three
      groups and the frequency of 199C was found to be significantly higher in the
      control group than in the IBS-D group (P = 0.03), but no significant difference
      in its frequency was found between the IBS-C group and controls. CONCLUSIONS:
      Patients with IBS-D have a higher incidence of SNPs in the mitochondrial D-loop
      than controls. The genotype 199C may be associated with a lower risk of IBS-D.

PMID- 29633534
TI  - Utility of pooled sequencing for association mapping in nonmodel organisms.
AB  - High-density genome-wide sequencing increases the likelihood of discovering genes
      of major effect and genomic structural variation in organisms. While there is an
      increasing availability of reference genomes across broad taxa, the greatest
      limitation to whole-genome sequencing of multiple individuals continues to be the
      costs associated with sequencing. To alleviate excessive costs, pooling multiple
      individuals with similar phenotypes and sequencing the homogenized DNA (Pool-Seq)
      can achieve high genome coverage, but at the loss of individual genotypes.
      Although Pool-Seq has been an effective method for association mapping in model
      organisms, it has not been frequently utilized in natural populations. To extend
      bioinformatic tools for rapid implementation of Pool-Seq data in nonmodel
      organisms, we developed a pipeline called PoolParty and illustrate its
      effectiveness in genetic association mapping. Alignment expectations based on
      five pooled Chinook salmon (Oncorhynchus tshawytscha) libraries showed that
      approximately 48% genome coverage per library could be achieved with reasonable
      sequencing effort. We additionally examined male and female O. tshawytscha
      libraries to illustrate how Pool-Seq techniques can successfully map known genes
      associated with functional differences among sexes such as growth hormone 2.
      Finally, we compared pools of individuals of different spawning ages for each sex
      to discover novel genes involved with age at maturity in O. tshawytscha such as
      opsin4 and transmembrane protein19. While not appropriate for every system, Pool
      Seq data processed by the PoolParty pipeline is a practical method for
      identifying genes of major effect in nonmodel organisms when high genome coverage
      is necessary and cost is a limiting factor.

PMID- 29633535
TI  - Dynamic changes in morphology, gene expression and microbiome in the jejunum of
      compensatory-growth rats induced by protein restriction.
AB  - We previously reported that protein-restricted rats experienced compensatory
      growth when they were switched to a normal protein diet (NPD). This study aimed
      to investigate the changes in gene expression and microbiome in the jejunum of
      compensatory-growth rats. Weaned Sprague-Dawley rats were assigned to an N group,
      an LN group and an L group. The rats in the L and N groups were fed a low protein
      diet (LPD) and the NPD respectively. The rats in the LN group were fed with the
      LPD for 2 weeks, followed by the NPD. The experiment lasted 70 days, and the rats
      were sacrificed for sampling on days 14, 28 and 70 to determine the jejunal
      morphology, microbiome and gene expression related to digestive, absorptive and
      barrier function. The results showed that, although rats in the LN group had
      temporarily impaired morphology and gene expression in the jejunum on day 14 in
      response to the LPD, they had improved jejunal morphology and gene expression
      related to jejunal function on day 28 compared to rats in the N group. This
      improvement might promote compensatory growth of rats. However, lower expression
      of genes related to nutrient absorption and undifferentiated villous height (VH)
      were observed in the jejunum of rats in the LN group on day 70. In contrast, rats
      in the L group had lower VH on day 28 and day 70, while the expression of
      absorptive genes increased on day 28 compared to rats in the N group.
      Additionally, dramatic microbial changes in the jejunum of compensatory-growth
      rats were observed, principally for Lactobacillus, Streptococcus, Corynebacterium
      and Staphylococcus. Moreover, the abundance of Lactobacillus, Streptococcus,
      Corynebacterium and Staphylococcus significantly correlated with gene expression
      in the jejunum as revealed by the correlation analysis.

PMID- 29633536
TI  - Diferrocenylmercury-Bridged Diphosphine: A Chiral, Ambiphilic, and Redox-Active
      Bidentate Ligand.
AB  - A diphosphine chelate ligand with a wide and flexible bite angle, a unique
      stereochemical environment, and redox-active and ambiphilic character is
      reported. Initially generated as its HgCl2 complex by reaction of 1,2-fc(PPh2
      )(SnMe3 ) (fc=ferrocenediyl) with HgCl2 in acetone, treatment with [n-Bu4 N]CN
      readily liberates the free chiral bidentate ligand. An intermolecular ClHg-Cl
      >Hgfc2 (2.9929(13) A) interaction that is unprecedented in ambiphilic ligand
      chemistry is seen in the solid structure of Hg(fcPPh2 )2 ?HgCl2 where the
      bridging mercury atom acts as a sigma-acceptor. Furthermore, a bis-[Rh(COD)Cl]
      complex is introduced, which displays relatively short Rh???Hg contacts of
      3.4765(5) and 3.4013(1) A. Wiberg indices of 0.12 are determined for these
      Rh???Hg interactions and an AIM analysis reveals bond paths with an electron
      density rho(r) of 1.2*10-2 and 1.4*10-2  e/a03 at the bond critical points.

PMID- 29633537
TI  - HiMAP: Robust phylogenomics from highly multiplexed amplicon sequencing.
AB  - High-throughput sequencing has fundamentally changed how molecular phylogenetic
      data sets are assembled, and phylogenomic data sets commonly contain 50- to 100
      fold more loci than those generated using traditional Sanger sequencing-based
      approaches. Here, we demonstrate a new approach for building phylogenomic data
      sets using single-tube, highly multiplexed amplicon sequencing, which we name
      HiMAP (highly multiplexed amplicon-based phylogenomics) and present bioinformatic
      pipelines for locus selection based on genomic and transcriptomic data resources
      and postsequencing consensus calling and alignment. This method is inexpensive
      and amenable to sequencing a large number (hundreds) of taxa simultaneously and
      requires minimal hands-on time at the bench (<1/2 day), and data analysis can be
      accomplished without the need for read mapping or assembly. We demonstrate this
      approach by sequencing 878 amplicons in single reactions for 82 species of
      tephritid fruit flies across seven genera (384 individuals), including some of
      the most economically important agricultural insect pests. The resulting filtered
      data set (>150,000-bp concatenated alignment, ~20% missing character sites across
      all individuals and amplicons) contained >40,000 phylogenetically informative
      characters, and although some discordance was observed between analyses, it
      provided unparalleled resolution of many phylogenetic relationships in this
      group. Most notably, we found high support for the generic status of Zeugodacus
      and the sister relationship between Dacus and Zeugodacus. We discuss HiMAP, with
      regard to its molecular and bioinformatic strengths, and the insight the
      resulting data set provides into relationships of this diverse insect group.

PMID- 29633538
TI  - Capital, Alienation, and Challenge: How U.S. Mexican Immigrant Students Build
      Pathways to College and Career Identities.
AB  - This article considers how the global "academic pipeline problem" constrains
      immigrant, low-income, and ethnic minority students' pathways to higher
      education, and how some students build pathways to college and career identities.
      After aligning theories of social capital, alienation/belonging, and challenge
      and their integration in Bridging Multiple Worlds Theory, we summarize six
      longitudinal studies based on this theory from a 23-year university-community
      partnership serving low-income, primarily U.S. Mexican immigrant youth. Spanning
      from childhood to early adulthood, the studies revealed two overarching findings:
      First, students built pathways to college and career identities while
      experiencing capital, alienation/belonging, and challenges across their evolving
      cultural worlds. Second, by "giving back" to families, peers, schools, and
      communities, students became cultural brokers and later, institutional agents,
      transforming institutional cultures. Findings highlight the value of integrating
      interdisciplinary theories, research evidence, and educational systems serving
      diverse communities to open individual pathways and academic pipelines in
      multicultural societies.

PMID- 29633539
TI  - Longterm Analysis of Biliary Complications After Duct-to-Duct Biliary
      Reconstruction in Living Donor Liver Transplantations.
AB  - Biliary complication (BC) is still regarded as the Achilles' heel of a living
      donor liver transplantation (LDLT). This study aims to evaluate the longterm
      outcomes of the duct-to-duct (DD) biliary reconstruction using 7-0 suture and to
      identify the risk factors of BCs after LDLTs. Data of 140 LDLTs between 2006 and
      2015 were analyzed. All biliary reconstructions were performed as DD anastomoses
      using 7-0 suture: 102 for the right lobe, 20 for the left lobe, and 18 for right
      posterior sector grafts. BC was defined as a bile leakage (BL) or a biliary
      stricture (BS), and the median follow-up time after LDLT was 65 months. A total
      of 19 recipients (13.5%) developed BCs (8 BLs and 16 BSs) after LDLT. The
      survival rates between recipients with and without BCs were 83% and 86.7%,
      respectively (P = 0.88). In univariate analyses, the risk factors for BC were
      small diameter of the graft's bile duct, long warm ischemic time, small graft-to
      recipient weight ratio, and no use of external biliary stent (EBS). The graft's
      bile duct diameter <= 3 mm and no use of EBS were determined as independent risk
      factors (hazard ratios of 9.74 and 7.68, respectively) in multivariate analyses.
      The 116 recipients with EBS had no BL, 11 had BSs (9%), while 24 without EBS had
      8 BLs (33%) and 5 BSs (21%). After a propensity score match between the
      recipients with and without EBS, the EBS group (24) developed only 1 BS (4%). In
      conclusion, DD anastomosis using 7-0 suture combined with EBS could provide
      favorable longterm outcomes after LDLT, which should thus be considered the
      surgical technique of choice for LDLTs.

PMID- 29633540
TI  - Factor analysis of the questionnaire of olfactory disorders in patients with
      chronic rhinosinusitis.
AB  - BACKGROUND: Olfactory-specific quality of life (QOL) can be measured using the
      Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS), which examines
      various aspects of olfactory dysfunction. It is unknown if certain factors of the
      QOD-NS differentially impact QOL. METHODS: Patients with chronic rhinosinusitis
      (CRS) completed the QOD-NS, 22-item Sino-Nasal Outcome Test (SNOT-22), Medical
      Outcomes Study Short Form 6-D (SF-6D) health utility measure, and Patient Health
      Questionnaire-2 (PHQ-2) depression screen. Exploratory factor analysis of the QOD
      NS was performed. Associations between QOD-NS factors and other QOL metrics were
      analyzed before and after endoscopic sinus surgery (ESS). RESULTS: Outcomes were
      examined on 132 patients. The QOD-NS contains 4 distinct factors. There was no
      difference in associations between the different factors and baseline clinical
      characteristics. ESS had greatest effect size (d) on factors 2 and 4 (d = 0.29
      and 0.27, respectively, p < 0.05). Postsurgical changes in the SF-6D and SNOT-22
      had the strongest correlation with factor 2 scores (r = 0.29 and 0.34,
      respectively, p < 0.05), and changes in the PHQ-2 had the strongest correlation
      to factor 3 (r = 0.24, p < 0.05). Abnormal QOD-NS scores at baseline were
      associated with effect size increases of 50% to 100% (p < 0.05). CONCLUSION: The
      QOD-NS measures 4 distinct factors. Eating-related questions had the greatest
      improvement after ESS. Health utility and CRS-specific QOL improvement most
      strongly associated with factor 2, while PHQ-2 changes are most highly associated
      with factor 3, suggesting a differential impact of the factors of the QOD-NS on
      varying aspects of QOL.

PMID- 29633541
TI  - Tuning the Hydrophobicity of a Mitochondria-Targeted NO Photodonor.
AB  - A few compounds in which the nitric oxide (NO) photodonor N-[4-nitro-3
      (trifluoromethyl)phenyl]propane-1,3-diamine is joined to the mitochondria
      targeting alkyltriphenylphosphonium moiety via flexible spacers of variable
      length were synthesized. The lipophilicity of the products was evaluated by
      measuring their partition coefficients in n-octanol/water. The obtained values,
      markedly lower than those calculated, are consistent with the likely collapsed
      conformation assumed by the compounds in solution, as suggested by molecular
      dynamics simulations. The capacity of the compounds to release NO under visible
      light irradiation was evaluated by measuring nitrite production by means of the
      Griess reaction. The accumulation of compounds in the mitochondria of human lung
      adenocarcinoma A549 cells was assessed by UPLC-MS. Interestingly, compound 13 [(9
      ((3-((4-nitro-3-(trifluoromethyl)phenyl)amino)propyl)amino)-9-oxononyl)
      triphenylphosphonium bromide] displayed both the highest accumulation value and
      high toxicity toward A549 cells upon irradiation-mediated NO release in
      mitochondria.

PMID- 29633543
TI  - Simultaneous detection and quantitation of organic impurities in methamphetamine
      by ultra-high-performance liquid chromatography-tandem mass spectrometry, a
      complementary technique for methamphetamine profiling.
AB  - The analysis of organic impurities plays an important role in the impurity
      profiling of methamphetamine, which in turn provides valuable information about
      methamphetamine manufacturing, in particular its synthetic route, chemicals, and
      precursors used. Ultra-high-performance liquid chromatography-tandem mass
      spectrometry (UHPLC-MS/MS) is ideally suited for this purpose due to its
      excellent sensitivity, selectivity, and wide linear range in multiple reaction
      monitoring (MRM) mode. In this study, a dilute-and-shoot UHPLC-MS/MS method was
      developed for the simultaneous identification and quantitation of 23 organic
      manufacturing impurities in illicit methamphetamine. The developed method was
      validated in terms of stability, limit of detection (LOD), lower limit of
      quantification (LLOQ), accuracy, and precision. More than 100 illicitly prepared
      methamphetamine samples were analyzed. Due to its ability to detect
      ephedrine/pseudoephedrine and its high sensitivity for critical target markers
      (eg, chloro-pseudoephedrine, N-cyclohexylamphetamine, and compounds B and P),
      more impurities and precursor/pre-precursors were identified and quantified
      versus the current procedure by gas chromatography-mass spectrometry (GC-MS).
      Consequently, more samples could be classified by their synthetic routes.
      However, the UHPLC-MS/MS method has difficulty in detecting neutral and
      untargeted emerging manufacturing impurities and can therefore only serve as a
      complement to the current method. Despite this deficiency, the quantitative
      information acquired by the presented UHPLC-MS/MS methodology increased the
      sample discrimination power, thereby enhancing the capacity of methamphetamine
      profiling program (MPP) to conduct sample-sample comparisons.

PMID- 29633542
TI  - Quality assurance of geometric accuracy based on an electronic portal imaging
      device and log data analysis for Dynamic WaveArc irradiation.
AB  - The purpose of this study was to develop a simple verification method for the
      routine quality assurance (QA) of Dynamic WaveArc (DWA) irradiation using
      electronic portal imaging device (EPID) images and log data analysis. First, an
      automatic calibration method utilizing the outermost multileaf collimator (MLC)
      slits was developed to correct the misalignment between the center of the EPID
      and the beam axis. Moreover, to verify the detection accuracy of the MLC position
      according to the EPID images, various positions of the MLC with intentional
      errors in the range 0.1-1 mm were assessed. Second, to validate the geometric
      accuracy during DWA irradiation, tests were designed in consideration of three
      indices. Test 1 evaluated the accuracy of the MLC position. Test 2 assessed dose
      output consistency with variable dose rate (160-400 MU/min), gantry speed (2.2-6
      degrees /s), and ring speed (0.5-2.7 degrees /s). Test 3 validated dose output
      consistency with variable values of the above parameters plus MLC speed (1.6-4.2
      cm/s). All tests were delivered to the EPID and compared with those obtained
      using a stationary radiation beam with a 0 degrees  gantry angle. Irradiation log
      data were recorded simultaneously. The 0.1-mm intentional error on the MLC
      position could be detected by the EPID, which is smaller than the EPID pixel
      size. In Test 1, the MLC slit widths agreed within 0.20 mm of their exposed
      values. The averaged root-mean-square error (RMSE) of the dose outputs was less
      than 0.8% in Test 2 and Test 3. Using log data analysis in Test 3, the RMSE
      between the planned and recorded data was 0.1 mm, 0.12 degrees , and 0.07 degrees
      for the MLC position, gantry angle, and ring angle, respectively. The proposed
      method is useful for routine QA of the accuracy of DWA.

PMID- 29633544
TI  - Multiscale FEM simulations of cross-linked actin network embedded in cytosol with
      the focus on the filament orientation.
AB  - The present contribution focuses on the application of the multiscale finite
      element method to the modeling of actin networks that are embedded in the
      cytosol. These cell components are of particular importance with regard to the
      cell response to external stimuli. The homogenization strategy chosen uses the
      Hill-Mandel macrohomogeneity condition for bridging 2 scales: the macroscopic
      scale that is related to the cell level and the microscopic scale related to the
      representative volume element. For the modeling of filaments, the Holzapfel-Ogden
      beta-model is applied. It provides a relationship between the tensile force and
      the caused stretches, serves as the basis for the derivation of the stress and
      elasticity tensors, and enables a novel finite element implementation. The
      elements with the neo-Hookean constitutive law are applied for the simulation of
      the cytosol. The results presented corroborate the main advantage of the concept,
      namely, its flexibility with regard to the choice of the representative volume
      element as well as of macroscopic tests. The focus is particularly placed on the
      study of the filament orientation and of its influence on the effective behavior.

PMID- 29633545
TI  - Challenges to controlling rabies in skunk populations using oral rabies
      vaccination: A review.
AB  - Controlling rabies in skunk populations is an important public health concern in
      many parts of the United States due to the potential for skunk rabies outbreaks
      in urban centres and the possible role for skunks in raccoon rabies variant
      circulation. Oral rabies vaccination (ORV) programmes have supported wildlife
      rabies control efforts globally but using ORV to control rabies in skunk
      populations has proven more challenging than with other target species, like
      foxes, coyotes and raccoons. A review of published studies found that some ORV
      constructs are immunogenic in skunks and protect against virulent rabies virus
      challenges, especially when delivered by direct installation into the oral
      cavity. However, in field ORV programmes using currently available vaccine-bait
      formats and distribution methods targeting other rabies reservoir species, skunks
      often fail to seroconvert. Field effectiveness of ORV in skunks appears to be
      limited by poor bait uptake or inadequate ingestion of vaccine rather than from
      poor vaccine efficacy. Observations of captive skunks revealed vaccine spillage
      when handling and biting into baits such that modification of bait formats might
      improve field effectiveness. In addition, a dose-response relationship between
      bait distribution density and post-baiting seroconversion among skunks was
      observed across the limited number of field studies. Additional research is
      needed to identify opportunities to modify ORV baits and distribution strategies
      to improve the viability of ORV as a rabies control strategy in skunks.

PMID- 29633547
TI  - Crystal Adaptronics: Mechanically Reconfigurable Elastic and Superelastic
      Molecular Crystals.
AB  - Mechanically reconfigurable molecular crystals-ordered materials that can adapt
      to variable operating and environmental conditions by deformation, whereby they
      attain motility or perform work-are quickly shaping a new research direction in
      materials science, crystal adaptronics. Properties such as elasticity,
      superelasticity, and ferroelasticity, which are normally related to inorganic
      materials, and phenomena such as shape-memory and self-healing effects, which are
      well-established for soft materials, are increasingly being reported for
      molecular crystals, yet their mechanism, quantification, and relation to the
      crystal structure of organic crystals are not immediately apparent. This
      Minireview provides a condensed topical overview of elastic, superelastic, and
      ferroelastic molecular crystals, new classes of materials that bridge the gap
      between soft matter and inorganic materials. The occurrence and detection of
      these unconventional properties, and the underlying structural features of the
      related molecular materials are discussed and highlighted with selected prominent
      recent examples.

PMID- 29633546
TI  - The pattern of 1-aminocyclopropane-1-carboxylate oxidase induction in the tomato
      leaf petiole abscission zone is independent of expression of the ribonuclease-LX
      encoding LeLX gene.
AB  - The abscission of tomato leaves occurs in the petiole abscission zone, and its
      late stage includes two spatially divided processes: cell separation and
      programmed cell death (PCD). Both of these processes are regulated by ethylene.
      The last step in ethylene biosynthesis is conversion of 1-aminocyclopropane-1
      carboxylic acid to ethylene, which is catalysed by the enzyme 1-aminocyclopropane
      1-carboxylate oxidase (ACO); however, the location of ACO in the leaf petiole
      abscission zone is not known. The tomato gene LeLX encodes ribonuclease LX, which
      is a marker for PCD and is induced by ethylene during abscission, but its
      association with ACO has not been explored. In a tomato transgenic line 1-7 with
      inhibited expression of LeLX showing delayed leaf abscission, the morphology and
      ultrastructure of the leaf petiole abscission zone was examined. In this zone of
      the cv.'VF36' and of a transgenic line 1-7, spatiotemporal differences in
      expression of LeACO1 and LeACO4 were analysed and ACO protein was detected
      immunohistochemically. In comparison to wild-type plants, there were no obvious
      morphological and ultrastructural features in the abscission zone of plants of a
      transgenic line 1-7 before and after abscission induction. LeACO1 expression was
      low before abscission induction, and increased 24 h after induction, although
      with no apparent spatial pattern. In contrast, LeACO4 was expressed before
      abscission induction, and its transcript level declined 24 h after induction on
      the distal side of the abscission zone fracture. In the LeLX-inhibited transgenic
      line, there were no significant differences in LeACO1 and LeACO4 expression in
      the petiole abscission zone, in comparison to wild-type plants. In addition, the
      ACO protein was immunolocalised to the vascular tissues that traverse the petiole
      abscission zone in plants of wild type and of a transgenic line 1-7; and
      additionally in the plane of future abscission zone fracture of transgenic-line
      plants. The results suggest temporal differential expression of the LeACO genes
      in tomato leaf petioles and vascular localisation of ACO1 protein. Additionally,
      the results indicate that expression of LeACO genes is not affected by
      suppression of the LeLX expression.

PMID- 29633548
TI  - Transmission of breast cancer by a single multiorgan donor to 4 transplant
      recipients.
AB  - We report 4 cases of breast cancer transmission to transplant recipients from a
      single organ donor that occurred years after donation. The diagnosis of breast
      cancer was occult at the time of donation. All of the recipients developed a
      histologically similar type of breast cancer within 16 months to 6 years after
      transplantation. Three out of 4 recipients died as a result of widely
      metastasized disease. One of the recipients survived after transplant nephrectomy
      followed by cessation of immunosuppression and chemotherapy. This extraordinary
      case points out the often fatal consequences of donor-derived breast cancer and
      suggests that removal of the donor organ and restoration of immunity can induce
      complete remission.

PMID- 29633549
TI  - "Dropping Out is Not an Option": How Educationally Resilient First-Generation
      Students See the Future.
AB  - First-generation college students (FGCS) often have different cultural values,
      practices, and goals from those of students from college-going families. As they
      navigate college, FGCS coordinate these values, practices, and goals with those
      of their families, noncollege-going friends, and communities. We draw on
      longitudinal and cross-sectional studies of FGCS attending a public university in
      California to address three research questions: (1) What challenges do FGCS face
      in their transition to and through college?; (2) What resources do they use to
      surmount these challenges?; and (3) What is the association between FGCS'
      resources and challenges and their academic persistence and career goals? Results
      showed that FGCS who surmounted challenges and persisted toward graduation had
      emotional support from family and friends from home; developed supportive
      relationships with university peers, staff, and faculty; and believed that
      college would allow them to attain their future life and career goals.

PMID- 29633550
TI  - Preventing discrimination based on psychiatric risk biomarkers.
AB  - Recent studies have identified genomic and nongenomic psychiatric risk biomarkers
      (PRBs; e.g., genomic variants, blood analytes, gray matter volume). PRBs may soon
      become a powerful tool for improving psychiatric care and prevention. PRB
      research and its translation to clinical care, however, may prove to be a double
      edged sword. Mental health stigma and discrimination are already widespread, and
      data caution that biological explanations of psychiatric disorders can exacerbate
      these stigmatizing attitudes, increasing the desire for social distance and
      heightening the perceived dangerousness of the patient. As a reaction to the
      Human Genome Project and historical concerns about eugenics, the international
      community mobilized to establish legislation to prevent genomic discrimination.
      But in most countries, these laws are limited to few contexts (e.g., employment,
      health insurance), and very few countries protect against discrimination based on
      nongenomic risk biomarkers. Like genomic PRBs, nongenomic PRBs provide
      information regarding risk for stigmatized psychiatric disorders and have similar
      and in some cases greater-predictive value. Numerous large-scale neuroscience and
      neurogenomics projects are advancing the identification and translation of PRBs.
      The prospect of PRB-based stigma however, threatens to undermine the potential
      benefits of this research. Unbridaled by nonexistent or limited PRB anti
      discrimination protections, the threat of PRB-based stigma and discrimination may
      lead many to forego PRB testing, even if shown to have clinical utility. To
      maximize the clinical and social benefits of PRB-based technologies, educational
      campaigns should address mental health and PRB stigma, and lawmakers should
      carefully consider expanding legislation that prohibits PRB-based discrimination.

PMID- 29633551
TI  - The single berberine bridge enzyme homolog of Physcomitrella patens is a
      cellobiose oxidase.
AB  - : The berberine bridge enzyme from the California poppy Eschscholzia californica
      (EcBBE) catalyzes the oxidative cyclization of (S)-reticuline to (S)-scoulerine,
      that is, the formation of the berberine bridge in the biosynthesis of
      benzylisoquinoline alkaloids. Interestingly, a large number of BBE-like genes
      have been identified in plants that lack alkaloid biosynthesis. This finding
      raised the question of the primordial role of BBE in the plant kingdom, which
      prompted us to investigate the closest relative of EcBBE in Physcomitrella patens
      (PpBBE1), the most basal plant harboring a BBE-like gene. Here, we report the
      biochemical, structural, and in vivo characterization of PpBBE1. Our studies
      revealed that PpBBE1 is structurally and biochemically very similar to EcBBE. In
      contrast to EcBBE, we found that PpBBE1 catalyzes the oxidation of the
      disaccharide cellobiose to the corresponding lactone, that is, PpBBE1 is a
      cellobiose oxidase. The enzymatic reaction mechanism was characterized by a
      structure-guided mutagenesis approach that enabled us to assign a catalytic role
      to amino acid residues in the active site of PpBBE1. In vivo experiments revealed
      the highest level of PpBBE1 expression in chloronema, the earliest stage of the
      plant's life cycle, where carbon metabolism is strongly upregulated. It was also
      shown that the enzyme is secreted to the extracellular space, where it may be
      involved in later steps of cellulose degradation, thereby allowing the moss to
      make use of cellulose for energy production. Overall, our results suggest that
      the primordial role of BBE-like enzymes in plants revolved around primary
      metabolic reactions in carbohydrate utilization. DATABASE: Structural data are
      available in the PDB under the accession numbers 6EO4 and 6EO5.

PMID- 29633552
TI  - What do clinicians need to watch for with direct-acting antiviral therapy?
AB  - INTRODUCTION: The introduction of drugs targeting the virus replication cycle has
      revolutionized treatment of chronic hepatitis C virus. These drugs, called direct
      acting antivirals, have brought about extremely high rates of virological cure
      and have increased the number of patients who can receive treatment due to the
      lack of absolute contraindications. A combination of different classes of direct
      acting antivirals is the current standard of care. Although treatment
      administration and monitoring has been simplified in recent years, it is still
      relatively complex and mostly in the hands of specialists. Several factors must
      be assessed before starting treatment to maximize efficacy and minimize side
      effects of treatment. In this review, we describe the factors that impact on the
      efficacy and safety of antiviral treatment for hepatitis C and provide clear
      recommendations for clinicians prescribing direct-acting antivirals. METHODS: We
      reviewed literature to define best practice, based on factors associated with
      treatment efficacy and safety data to recommend treatment options, baseline and
      on-treatment assessments. The review included searches in PubMed, and the
      abstracts presented at the International Liver Congress TM and The Liver Meeting
      TM between January 2013 and September 2017. RESULTS: Clinical features that must
      be assessed before starting treatment include virological factors, such as
      hepatitis C virus genotype, HIV and hepatitis B coinfection and host factors,
      such as concomitant medications, liver disease stage and renal function.
      CONCLUSIONS: Patients who start antiviral treatment for chronic hepatitis C
      require a thorough clinical evaluation. There is a need for assessing factors
      that impact on the treatment schedule and duration or affect the pharmacokinetics
      of direct-acting antivirals.

PMID- 29633553
TI  - Toxicological Aspects of the Essential Oil from Cinnamodendron dinisii.
AB  - The objective of this study was to determine cytotoxic activity, hemolytic
      activity, and to evaluate the ability of the essential oil from Cinnamodendron
      dinisii to induce DNA fragmentation of human lymphocytes. The essential oil was
      obtained by hydrodistillation. Cytotoxic activity was determined by the MTT
      method. Hemolytic activity was evaluated by spectrophotometric quantification of
      hemoglobin released by erythrocytes. Damage to lymphocyte DNA molecules was
      assessed by the Comet assay. The essential oil under study showed high cytotoxic
      activity on Vero cells (CC50 = 35.72 MUg/mL) and induced hemolysis in both
      hematocrits, besides leading to the oxidation of hemoglobin released. The
      genotoxic activity of C. dinisii essential oil was also observed, which induced
      concentration-dependent DNA fragmentation of human lymphocytes and, at 50 MUL/mL,
      it was more active than the positive control. The essential oil from C. dinisii
      has a toxic action, suggesting a special attention in the application of this oil
      to health-promoting activities; however, among its components, there are
      molecules with potential for future application in anticancer therapies.

PMID- 29633554
TI  - The Rocky Road to viral hepatitis elimination: assuring access to antiviral
      therapy for ALL coinfected patients from low- to high-income settings.

PMID- 29633555
TI  - Microbial rRNA gene expression and co-occurrence profiles associate with
      biokinetics and elemental composition in full-scale anaerobic digesters.
AB  - This study examined whether the abundance and expression of microbial 16S rRNA
      genes were associated with elemental concentrations and substrate conversion
      biokinetics in 20 full-scale anaerobic digesters, including seven municipal
      sewage sludge (SS) digesters and 13 industrial codigesters. SS digester contents
      had higher methane production rates from acetate, propionate and phenyl acetate
      compared to industrial codigesters. SS digesters and industrial codigesters were
      distinctly clustered based on their elemental concentrations, with higher
      concentrations of NH3 -N, Cl, K and Na observed in codigesters. Amplicon
      sequencing of 16S rRNA genes and reverse-transcribed 16S rRNA revealed divergent
      grouping of microbial communities between mesophilic SS digesters, mesophilic
      codigesters and thermophilic digesters. Higher intradigester distances between
      Archaea 16S rRNA and rRNA gene profiles were observed in mesophilic codigesters,
      which also had the lowest acetate utilization biokinetics. Constrained ordination
      showed that microbial rRNA and rRNA gene profiles were significantly associated
      with maximum methane production rates from acetate, propionate, oleate and phenyl
      acetate, as well as concentrations of NH3 -N, Fe, S, Mo and Ni. A co-occurrence
      network of rRNA gene expression confirmed the three main clusters of anaerobic
      digester communities based on active populations. Syntrophic and methanogenic
      taxa were highly represented within the subnetworks, indicating that obligate
      energy-sharing partnerships play critical roles in stabilizing the digester
      microbiome. Overall, these results provide new evidence showing that different
      feed substrates associate with different micronutrient compositions in anaerobic
      digesters, which in turn may influence microbial abundance, activity and
      function.

PMID- 29633556
TI  - Are Value-Neutrality and Value-Engagement Properties of Social Actors or Social
      Moments?

PMID- 29633558
TI  - The evolution of empathy and devo-evo-What is the connection?

PMID- 29633557
TI  - Subcutaneous administration of a neutralizing IL-1beta antibody prolongs limb
      allograft survival.
AB  - Cytokine-expression profiles revealed IL-1beta highly upregulated in rejecting
      skin of limb allografts. We investigate the effect of intragraft treatment with a
      neutralizing IL-1beta antibody in limb transplantation. Following allogenic hind
      limb transplantation, Lewis rats were either left untreated or treated with anti
      lymphocyte serum + tacrolimus (baseline); baseline immunosuppression + anti-IL
      1beta (1 mg/kg once/week, 6-8 subcutaneous injections) into the transplanted or
      contralateral limb. Endpoint was rejection grade III or day 100. Graft rejection
      was assessed by histology, immunohistochemistry, flow cytometry phenotyping of
      immune cells, and monitoring cytokine expression. Anti-IL-1beta injections into
      the allograft or contralateral limb resulted in a significant delay of rejection
      onset (controls: 58.60 +/- 0.60; group 3: 75.80 +/- 10.87, P = .044; group 4:
      73.00 +/- 6.49, P = .008) and prolongation of graft survival (controls: 64.60 +/-
      0.87; group 3: 86.60 +/- 5.33, P = .002; group 4: 93.20 +/- 3.82, P = .002),
      compared to controls. Although the phenotype of the graft infiltrating immune
      cells did not differ between groups, significantly decreased skin protein levels
      of IL-1beta, IL-4, IL-13, IP-10, MCP-1, and MCP-3 in long-term-survivors indicate
      an overall decrease of chemoattraction and infiltration of immune cells as the
      immunosuppressive mechanism of anti-IL-1beta. Inhibition of IL-1beta with short
      term systemic immunosuppression prolongs limb allograft survival and represents a
      promising target for immunosuppression in extremity transplantation.

PMID- 29633559
TI  - Linkage and retention in HCV care for HIV-infected populations: early data from
      the DAA era.
AB  - INTRODUCTION: There is currently no published data on the effectiveness of DAA
      treatment for elimination of HCV infection in HIV-infected populations at a
      population level. However, a number of relevant studies and initiatives are
      emerging. This research aims to report cascade of care data for emerging HCV
      elimination initiatives and studies that are currently being evaluated in HIV/HCV
      co-infected populations in the context of implementation science theory. METHODS:
      HCV elimination initiatives and studies in HIV co-infected populations that are
      currently underway were identified. Context, intervention characteristics and
      cascade of care data were synthesized in the context of implementation science
      frameworks. RESULTS: Seven HCV elimination initiatives and studies were
      identified in HIV co-infected populations, mainly operating in high-income
      countries. Four were focused mainly on HCV elimination in HIV-infected gay and
      bisexual men (GBM), and three included a combination of people who inject drugs
      (PWID), GBM and other HIV-infected populations. None were evaluating treatment
      delivery in incarcerated populations. Overall, HCV RNA was detected in 4894 HIV
      infected participants (range within studies: 297 to 994): 48% of these initiated
      HCV treatment (range: 21% to 85%; within studies from a period where DAAs were
      broadly available the total is 57%, range: 36% to 74%). Among studies with
      treatment completion data, 96% of 1109 initiating treatment completed treatment
      (range: 94% to 99%). Among those who could be assessed for sustained virological
      response at 12 weeks (SVR12), 1631 of 1757 attained SVR12 (93%, range: 86% to
      98%). CONCLUSIONS: Early results from emerging research on HCV elimination in HIV
      infected populations suggest that HCV treatment uptake is higher than reported
      levels prior to DAA treatment availability, but approximately half of patients
      remain untreated. These results are among diagnosed populations and additional
      effort is required to increase diagnosis rates. Among those who have initiated
      treatment, completion and SVR rates are promising. More data are required in
      order to evaluate the effectiveness of these elimination programmes in the long
      term, assess which intervention components are effective, and whether they need
      to be tailored to particular population groups.

PMID- 29633560
TI  - Is hepatitis C virus elimination possible among people living with HIV and what
      will it take to achieve it?
AB  - INTRODUCTION: The World Health Organization targets for hepatitis C virus (HCV)
      elimination include a 90% reduction in new infections by 2030. Our objective is
      to review the modelling evidence and cost data surrounding feasibility of HCV
      elimination among people living with HIV (PLWH), and identify likely components
      for elimination. We also discuss the real-world experience of HCV direct acting
      antiviral (DAA) scale-up and elimination efforts in the Netherlands. METHODS: We
      review modelling evidence of what intervention scale-up is required to achieve
      WHO HCV elimination targets among HIV-infected (HIV+) people who inject drugs
      (PWID) and men who have sex with men (MSM), review cost-effectiveness of HCV
      therapy among PLWH and discuss economic implications of elimination. We
      additionally use the real-world experience of DAA scale-up in the Netherlands to
      illustrate the promise and potential challenges of HCV elimination strategies in
      MSM. Finally, we summarize key components of the HCV elimination response among
      PWLH. RESULTS AND DISCUSSION: Modelling indicates HCV elimination among HIV+ MSM
      and PWID is potentially achievable but requires combination treatment and either
      harm reduction or behavioural risk reductions. Preliminary modelling indicates
      elimination among HIV+ PWID will require elimination efforts among PWID more
      broadly. Treatment for PLWH and high-risk populations (PWID and MSM) is cost
      effective in high-income countries, but costs of DAAs remain a barrier to scale
      up worldwide despite the potential low production price ($50 per 12 week course).
      In the Netherlands, universal DAA availability led to rapid uptake among HIV+ MSM
      in 2015/16, and a 50% reduction in acute HCV incidence among HIV+ MSM from 2014
      to 2016 was observed. In addition to HCV treatment, elimination among PLWH
      globally also likely requires regular HCV testing, development of low-cost
      accurate HCV diagnostics, reduced costs of DAA therapy, broad treatment access
      without restrictions, close monitoring for HCV reinfection and retreatment, and
      harm reduction and/or behavioural interventions. CONCLUSIONS: Achieving WHO HCV
      Elimination targets is potentially achievable among HIV-infected populations.
      Among HIV+ PWID, it likely requires HCV treatment scale-up combined with harm
      reduction for both HIV+ and HIV- populations. Among HIV+ MSM, elimination likely
      requires both HCV treatment and behaviour risk reduction among the HIV+ MSM
      population, the latter of which to date has not been observed. Lower HCV
      diagnostic and treatment costs will be key to ensuring scale-up of HCV testing
      and treatment without restriction, enabling elimination.

PMID- 29633561
TI  - Approaches for simplified HCV diagnostic algorithms.
AB  - INTRODUCTION: In the light of the advances in HCV antiviral therapy, global
      control of HCV infection becomes feasible but depends on the capacity of
      countries to identify infected people and to offer them treatment. To achieve the
      WHO goal which targets a diagnosis rate of 90% by 2030, simplification of
      screening and diagnosis will be crucial. METHODS: Published literature,
      unpublished data and expert consensus were used to determine key parameters,
      including point-of-care, rapid diagnostic testing, screening, the use of HCV core
      Ag and dried blood spots; starting from 2008 until November 2017. In addition, a
      manual search was undertaken to detect relevant papers or websites related to
      specific data from countries which underwent or are planning a programme of HCV
      elimination. RESULTS: Several strategies have been developed and evaluated these
      last years to simplify and facilitate access to screening and diagnosis, the
      development of reliable HCV core antigen tests and new nucleic acid amplification
      technologies for use in decentralized settings. In high prevalence settings, a
      one-step screening and diagnosis strategy could simplify diagnostic algorithms
      provided the cost is reduced. Finally, genotyping may no longer be required in
      the context of availability of pangenotypic antiviral therapy. CONCLUSIONS:
      Despite relevant advances in HCV screening and diagnosis, the overall diagnosis
      package is still too expensive today and efforts must be made to allow
      generalized implementation of reliable tests in low and middle income countries.
      These efforts will be key factors to foster a real public health approach to HCV
      elimination.

PMID- 29633562
TI  - Hep-CORE: a cross-sectional study of the viral hepatitis policy environment
      reported by patient groups in 25 European countries in 2016 and 2017.
AB  - INTRODUCTION: The first World Health Organization (WHO) global health sector
      strategy on hepatitis B and C viruses (HBV and HCV) has called for the
      elimination of viral hepatitis as a major public health threat by 2030. This
      study assesses policies and programmes in support of elimination efforts as
      reported by patient groups in Europe. METHODS: In 2016 and 2017, hepatitis
      patient groups in 25 European countries participated in a cross-sectional survey
      about their countries' policy responses to HBV and HCV. The English-language
      survey addressed overall national response; public awareness/engagement; disease
      monitoring; prevention; testing/diagnosis; clinical assessment; and treatment. We
      performed a descriptive analysis of data and compared 2016 and 2017 findings.
      RESULTS: In 2017, 72% and 52% of the 25 European study countries were reported to
      not have national HBV and HCV strategies respectively. The number of respondents
      indicating that their governments collaborated with civil society on viral
      hepatitis control increased from 13 in 2016 to 18 in 2017. In both 2016 and 2017,
      patient groups reported that 9 countries (36%) have disease registers for HBV and
      11 (44%) have disease registers for HCV. The number of countries reported to have
      needle and syringe exchange programmes available in all parts of the country
      dropped from 10 (40%) in 2016 to 8 in 2017 (32%). In both 2016 and 2017, patient
      groups in 5 countries (20%) reported that HCV treatment is available in non
      hospital settings. From 2016 to 2017, the reported number of countries with no
      restrictions on access to direct-acting antivirals for HCV increased from 3 (12%)
      to 7 (28%), and 5 fewer countries were reported to refuse treatment to people who
      are currently injecting drugs. CONCLUSIONS: The patient-led Hep-CORE study offers
      a unique perspective on the readiness of study countries to undertake
      comprehensive viral hepatitis elimination efforts. Viral hepatitis monitoring
      should be expanded to address policy issues more comprehensively and to
      incorporate civil society perspectives, as is the case with global HIV
      monitoring. Policy components should also be explicitly added to the WHO
      framework for monitoring country-level progress against viral hepatitis.

PMID- 29633563
TI  - Mild hyperbaric oxygen inhibits the growth-related decline in skeletal muscle
      oxidative capacity and prevents hyperglycemia in rats with type 2 diabetes
      mellitus.
AB  - BACKGROUND: Humans and animals with type 2 diabetes mellitus (T2DM) exhibit low
      skeletal muscle oxidative capacity and impaired glucose metabolism. The aim of
      the present study was to investigate the effects of exposure to mild hyperbaric
      oxygen on these changes in obese rats with T2DM. METHODS: Five-week-old non
      diabetic Long-Evans Tokushima Otsuka (LETO) and diabetic Otsuka Long-Evans
      Tokushima Fatty (OLETF) rats were divided into normobaric (LETO-NB and OLETF-NB)
      and mild hyperbaric oxygen (LETO-MHO and OLETF-MHO) groups. The LETO-MHO and
      OLETF-MHO groups received 1266 hPa with 36% oxygen for 3 h daily for 22 weeks.
      RESULTS: Fasting and non-fasting blood glucose, HbA1c, and triglyceride levels
      were lower in the OLETF-MHO group than in the OLETF-NB group (P < 0.05). In the
      soleus muscle, peroxisome proliferator-activated receptor delta/beta
      (Ppardelta/beta), Ppargamma, and PPARgamma coactivator-1alpha (Pgc-1alpha) mRNA
      levels were lower in the OLETF-NB group than in all other groups (P < 0.05),
      whereas myogenin (Myog) and myogenic factor 5 (Myf5) mRNA levels were higher in
      the OLETF-MHO group than in the LETO-NB and OLETF-NB groups (P < 0.05). The
      soleus muscles in the OLETF-NB group contained only low-oxidative Type I fibers,
      whereas those in all other groups contained high-oxidative Type IIA and Type IIC
      fibers in addition to Type I fibers. CONCLUSIONS: Exposure to mild hyperbaric
      oxygen inhibits the decline in skeletal muscle oxidative capacity and prevents
      the hyperglycemia associated with T2DM. Pgc-1alpha, Myog, and Myf5 mRNA levels
      appear to be closely associated with skeletal muscle oxidative capacity in rats
      with T2DM.

PMID- 29633564
TI  - Research gaps in viral hepatitis.
AB  - INTRODUCTION: The World Health Organization has aimed for global elimination of
      both hepatitis B virus (HBV) and hepatitis C virus (HCV) by 2030. Treatments
      available to cure HCV and control HBV, as well as vaccination to prevent HBV
      infection, have certainly allowed for such bold goals, yet the final steps to
      usher in elimination require further evidence. DISCUSSION: We broadly discuss the
      needs for three major public health approaches. First, an effective vaccine
      exists for HBV and mass-vaccination campaigns have resulted in decreases in
      hepatitis B surface antigen seroprevalence and overall rates of liver-related
      morality. Still, HBV vaccination coverage is poor in certain regions of the
      world, while the reasons for such low coverage require further study. A
      prophylactic vaccine is probably needed to eliminate HCV, but is not being
      readily developed. Second, identifying HBV/HCV infected individuals remains a
      priority to increase awareness of disease status, particularly for key
      populations. Research evaluating large-scale implementation of novel, rapid and
      mobile point-of-care tests would be helpful to determine whether increased
      awareness is achievable in these settings. Third, antiviral therapy allows for
      strong HBV suppression and HCV cure, while its access depends on financial
      factors among many others. Although there is strong evidence to treat key
      populations and specific groups with progressed disease, as stated in current
      guidelines, the advantages of extending treatment eligibility to decrease onward
      spread of HBV/HCV infection and prevent further burden of disease are lacking
      "real world" evidence. Novel anti-HBV treatments are being developed to target
      intrahepatocellular HBV replication, but are still in the early phases of
      clinical development. Each of the strategies mentioned above has specific
      implications for HIV infection. CONCLUSIONS: There are certainly effective tools
      to combat the spread of viral hepatitis and treat infected individuals - yet how
      they are able to reach key populations, and the infrastructure required to do so,
      continue to represent the largest research gap when evaluating the progress
      towards elimination. Continuously adapted and informed research is required to
      establish the priorities in achieving elimination goals.

PMID- 29633566
TI  - Simple and efficient germline copy number variant visualization method for the
      Ion AmpliSeqTM custom panel.
AB  - BACKGROUND: Recent advances in molecular genetic analysis using next-generation
      sequencing (NGS) have drastically accelerated the identification of disease
      causing gene mutations. Most next-generation sequencing analyses of inherited
      diseases have mainly focused on single-nucleotide variants and short indels,
      although, recently, structure variations including copy number variations have
      come to be considered an important cause of many different diseases. However,
      only a limited number of tools are available for multiplex PCR-based target
      genome enrichment. METHODS: In this paper, we reported a simple and efficient
      copy number variation visualization method for Ion AmpliSeqTM target resequencing
      data. Unlike the hybridization capture-based target genome enrichment system, Ion
      AmpliSeqTM reads are multiplex PCR products, and each read generated by the same
      amplicon is quite uniform in length and position. Based on this feature, the
      depth of coverage information for each amplicon included in the barcode/amplicon
      coverage matrix file was used for copy number detection analysis. We also
      performed copy number analysis to investigate the utility of this method through
      the use of positive controls and a large Japanese hearing loss cohort. RESULTS:
      Using this method, we successfully confirmed previously reported copy number loss
      cases involving the STRC gene and copy number gain in trisomy 21 cases. We also
      performed copy number analysis of a large Japanese hearing loss cohort (2,475
      patients) and identified many gene copy number variants. The most prevalent copy
      number variation was STRC gene copy number loss, with 129 patients carrying this
      copy number variation. CONCLUSION: Our copy number visualization method for Ion
      AmpliSeqTM data can be utilized in efficient copy number analysis for the
      comparison of a large number of samples. This method is simple and requires only
      easy calculations using standard spread sheet software.

PMID- 29633567
TI  - Dirty Work, Dirty Resistance: Digital Warfare in the Era of Precarious Labor.
AB  - This qualitative content analysis of 723 anonymous reviews of 60 Canadian food
      service employers, posted on RateMyEmployer.ca, explores how digital spaces
      publically circulate precarious workers' resistances and management of
      occupational stigma. We introduce to literature on "dirty work" the concept of
      socioeconomic hygiene, which identifies a particular kind of social and moral
      order within which the positions of the subordinated are naturalized between the
      socially and morally "clean" and "unclean."

PMID- 29633568
TI  - Mix-and-match nanobiosensor design: Logical and spatial programming of biosensors
      using self-assembled DNA nanostructures.
AB  - The evergrowing need to understand and engineer biological and biochemical
      mechanisms has led to the emergence of the field of nanobiosensing. Structural
      DNA nanotechnology, encompassing methods such as DNA origami and single-stranded
      tiles, involves the base pairing-driven knitting of DNA into discrete one-, two-,
      and three-dimensional shapes at nanoscale. Such nanostructures enable a versatile
      design and fabrication of nanobiosensors. These systems benefit from DNA's
      programmability, inherent biocompatibility, and the ability to incorporate and
      organize functional materials such as proteins and metallic nanoparticles. In
      this review, we present a mix-and-match taxonomy and approach to designing
      nanobiosensors in which the choices of bioanalyte and transduction mechanism are
      fully independent of each other. We also highlight opportunities for greater
      complexity and programmability of these systems that are built using structural
      DNA nanotechnology. This article is categorized under: Implantable Materials and
      Surgical Technologies > Nanomaterials and Implants Diagnostic Tools > Biosensing
      Biology-Inspired Nanomaterials > Nucleic Acid-Based Structures Nanotechnology
      Approaches to Biology > Nanoscale Systems in Biology.

PMID- 29633565
TI  - Hfq chaperone brings speed dating to bacterial sRNA.
AB  - Hfq is a ubiquitous, Sm-like RNA binding protein found in most bacteria and some
      archaea. Hfq binds small regulatory RNAs (sRNAs), facilitates base pairing
      between sRNAs and their mRNA targets, and directly binds and regulates
      translation of certain mRNAs. Because sRNAs regulate many stress response
      pathways in bacteria, Hfq is essential for adaptation to different environments
      and growth conditions. The chaperone activities of Hfq arise from multipronged
      RNA binding by three different surfaces of the Hfq hexamer. The manner in which
      the structured Sm core of Hfq binds RNA has been well studied, but recent work
      shows that the intrinsically disordered C-terminal domain of Hfq modulates sRNA
      binding, creating a kinetic hierarchy of RNA competition for Hfq and ensuring the
      release of double-stranded sRNA-mRNA complexes. A combination of structural,
      biophysical, and genetic experiments reveals how Hfq recognizes its RNA
      substrates and plays matchmaker for sRNAs and mRNAs in the cell. The interplay
      between structured and disordered domains of Hfq optimizes sRNA-mediated post
      transcriptional regulation, and is a common theme in RNA chaperones. This article
      is categorized under: Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs RNA
      Interactions with Proteins and Other Molecules > RNA-Protein Complexes RNA
      Structure and Dynamics > RNA Structure, Dynamics, and Chemistry.

PMID- 29633569
TI  - Low molecular-weight fucoidan protects against hindlimb ischemic injury in type 2
      diabetic mice through enhancing endothelial nitric oxide synthase
      phosphorylation.
AB  - BACKGROUND: Diabetes mellitus (DM) complications are associated with ischemic
      injury. Angiogenesis is a therapeutic strategy for diabetic foot. The aim of this
      study was to investigate the possible angiogenic effect of low molecular weight
      fucoidan (LMWF) in diabetic peripheral arterial disease (PAD). METHODS: Diabetic
      db/db mice and age-matched C57BL/6 mice underwent femoral artery ligation
      followed by LMWF (30, 60, 80 mg/kg per day, p.o.) or cilostazol (30 mg/kg/day,
      p.o.) treatment for 6 weeks. Endothelium-dependent vasodilation and blood flow of
      the hindlimb were measured. Histological and western blot analyses of CD34,
      vascular endothelial growth factor (VEGF), eNOS, and inflammatory factors in the
      gastrocnemius were performed. The effects of LMWF were confirmed in human
      umbilical vein endothelial cells (HUVEC). RESULTS: Diabetic mice with ligation
      exhibited hindlimb ulceration, hydrosarca, and necrosis, increased expression of
      inflammatory factors, and decreased levels of VEGF and eNOS phosphorylation.
      Treatment with LMWF markedly ameliorated foot lesions, suppressed expression of
      inflammatory factors, and improved plantar perfusion by promoting endothelium
      dependent vasodilation and revascularization in diabetic PAD mice. In high
      glucose treated HUVEC, LMWF (40 MUg/mL) reversed blunted endothelial cell
      proliferation, migration, and tube formation, and promoted eNOS phosphorylation
      and VEGF expression, whereas HUVEC pretreatment with 100 MUmol/L NG -nitro-l
      arginine methyl ester, an eNOS antagonist, markedly inhibited the effects of
      LMWF. CONCLUSION: This study demonstrates that LMWF alleviates hindlimb ischemic
      damage, at least in part by promoting eNOS phosphorylation, nitric oxide
      production, and VEGF expression, resulting in enhanced angiogenesis in the
      ischemic region.

PMID- 29633570
TI  - Partial resection of the middle turbinate during endoscopic sinus surgery for
      chronic rhinosinusitis does not lead to an increased risk of empty nose syndrome:
      a cohort study of a tertiary practice.
AB  - BACKGROUND: The treatment of the middle turbinate (MT) during endoscopic sinus
      surgery (ESS) for chronic rhinosinusitis (CRS) remains a contentious issue with
      arguments both for and against its resection. The purpose of this study was to
      examine the clinical impact of partial MT resection (PMTR) during ESS, paying
      particular attention to the risk of developing empty nose syndrome (ENS) and
      alteration to olfaction. METHODS: This cohort study was performed on
      prospectively collected data. A total of 177 patients underwent ESS for CRS; 93
      had PMTR and 84 MT preservation (MTP). Preoperative data collection included
      subjective symptom scores as per the Adelaide Disease Severity Score (ADSS), Lund
      Mackay scores, and nasal polyp status. The Empty Nose Syndrome 6-Item
      Questionnaire (ENS6Q) was administered by telephone consultation and analyzed
      alongside postoperative symptom scores. RESULTS: There was no difference in ENS6Q
      scores in patients who underwent PMTR vs those who had MTP. Patients who
      underwent PMTR had a higher baseline disease on Lund-Mackay scoring, and were
      more likely to be nasal polyp patients and be undergoing revision surgery. ADSS
      scores demonstrated significant improvements in all rhinologic symptoms, with no
      difference between the cohorts. CONCLUSION: PMTR is an adjunctive procedure to
      ESS. This study has established that PMTR as performed by the senior author
      carries no additional risk of developing ENS symptoms as defined by the ENS6Q,
      and that it carries no additional risk to olfaction or other rhinologic symptoms.
      PMTR can be safely considered at time of ESS, especially in patients at risk of
      lateralization of the MT.

PMID- 29633572
TI  - Automated identification of structurally heterogeneous and patentable
      antiproliferative hits as potential tubulin inhibitors.
AB  - By employing a recently developed hierarchical computational platform, we
      identified 37 novel and structurally diverse tubulin targeting compounds. In
      particular, hierarchical molecular filters, based on molecular shape similarity,
      structure-based pharmacophore, and molecular docking, were applied on a large
      chemical collection of commercial compounds to identify unexplored and patentable
      microtubule-destabilizing candidates. The herein proposed 37 novel hits, showing
      new molecular scaffolds (such as 1,3,3a,4-tetraaza-1,2,3,4,5,6,7,7a
      octahydroindene or dihydropyrrolidin-2-one fused to a chromen-4-one), are
      provided with antiproliferative activity in the MUm range toward MCF-7 (human
      breast cancer lines). Importantly, there is a likely causative relationship
      between cytotoxicity and the inhibition of tubulin polymerization at the
      colchicine binding site, assessed through fluorescence polymerization assays.

PMID- 29633571
TI  - ERCC6L2-associated inherited bone marrow failure syndrome.
AB  - BACKGROUND: ERCC6L2-associated disorder has recently been described and only five
      patients were reported so far. The described phenotype included bone marrow,
      cerebral, and craniofacial abnormalities. The aim of this study was to further
      define the genetic and phenotypic spectrum of the disorder by summarizing the
      five published cases and an additional case that we identified through whole
      exome sequencing performed at the University of Toronto. METHODS: Clinical data
      was extracted from the Canadian Inherited Marrow Failure Registry. Whole exome
      sequencing was performed to identify causative mutations. RESULTS: All six cases
      had homozygous truncating mutations either at or upstream of the helicase domain
      of ERCC6L2. All patients displayed bone marrow failure, learning or developmental
      delay and microcephaly. Our patient was unique in displaying features of
      cerebellar disease, including ataxia and dysmetria as well as an interval
      deterioration of the corpus callosum and generalized volume loss on MRI. Another
      unique feature of our patient was retinal dystrophy with macular involvement.
      Along with one other patient, our patient displayed craniofacial abnormalities by
      presenting with low-set prominent ears, a pointed prominent chin, and deep-set
      eyes. Leukemia is common among patients with inherited bone marrow failure, but
      thus far, none of the patients have developed this complication. CONCLUSIONS:
      ERCC6L2-associated disorder is a multisystem disorder. The phenotype spectrum
      includes bone marrow failure, cerebral, and craniofacial abnormalities, as well
      as cerebellar and retinal abnormalities.

PMID- 29633573
TI  - Does the second messenger cAMP have a more complex role in controlling
      filamentous fungal morphology and metabolite production?
AB  - The effect of second messenger cAMP on the physiological aspects of fungal cells
      such as pigmentation has been reported previously. However, their actual role in
      the cellular biochemical cascade that eventually affects the fungal growth
      morphology, such as mycelial pellet formation, is unclear. This article intends
      to open up the detailed study on the possible correlative effect of cAMP on the
      morphological and physiological growth aspects of filamentous fungi, with special
      emphasis on the industrial metabolite production.

PMID- 29633574
TI  - Morphological defects, sperm DNA integrity, and protamination of bovine
      spermatozoa.
AB  - The association between sperm morphology characteristics and DNA conformation and
      integrity is still controversial. In bulls, major morphological sperm
      abnormalities have been associated with reduced fertility, and morphological
      assessment is used to provide an indication of potential fertility of the
      individual. Sperm DNA fragmentation and damage has a negative effect on embryo
      development and subsequently fertility, with bull spermatozoa generally
      displaying low levels of DNA damage and tight chromatin. However, sensitive
      methods for detecting chromatin damage may reveal associations with morphological
      defects. The objective was to determine whether morphological sperm abnormalities
      and variables expressing sperm DNA integrity and protamination are correlated in
      bulls, using the sperm chromatin structure assay (SCSA) and the sperm protamine
      deficiency assay (SPDA). Electroejaculated samples (n = 1009) from two-year-old
      tropically adapted bulls were split and fixed and submitted to microscopic sperm
      morphology assessment, and snap-frozen for sperm nuclear integrity assessments by
      SPDA and SCSA. For SPDA, the variables were defective (MCB) and deprotaminated
      (HCB), and for SCSA, the variables were DNA fragmentation index (DFI) and high
      DNA stainability (HDS). HCB correlated with DFI; tauKen2  = 0.317 and HDS; 0.098,
      and MCB correlated with DFI; 0.183 (p < 0.001). The percentage of morphological
      normal spermatozoa was correlated negatively to DFI; tauKen2  = -0.168, MCB; 
      0.116 and HCB; -0.137 (p < 0.001). HCB and DFI were both positively correlated to
      head defects, proximal droplets, and spermatogenic immaturity, but not to distal
      droplets, vacuoles, or diadems. Sperm DNA integrity and protamination, using the
      SCSA and SPDA, respectively, in bulls show associations with morphological
      parameters, particularly with head shape abnormalities and indicators of
      spermatogenic immaturity, including proximal droplets. The vacuoles and diadem
      defects were not correlated with sperm nuclear integrity, and hence, these are
      likely physiological features that may not directly affect sperm chromatin
      configuration.

PMID- 29633575
TI  - Anaplastic lymphoma kinase (ALK) gene rearrangements in radiation-related human
      papillary thyroid carcinoma after the Chernobyl accident.
AB  - Childhood radiation exposure has been associated with increased papillary thyroid
      carcinoma (PTC) risk. The role of anaplastic lymphoma kinase (ALK) gene
      rearrangements in radiation-related PTC remains unclear, but STRN-ALK fusions
      have recently been detected in PTCs from radiation exposed persons after
      Chernobyl using targeted next-generation sequencing and RNA-seq. We investigated
      ALK and RET gene rearrangements as well as known driver point mutations in PTC
      tumours from 77 radiation-exposed patients (mean age at surgery 22.4 years) and
      PTC tumours from 19 non-exposed individuals after the Chernobyl accident. ALK
      rearrangements were detected by fluorescence in situ hybridisation (FISH) and
      confirmed with immunohistochemistry (IHC); point mutations in the BRAF and RAS
      genes were detected by DNA pyrosequencing. Among the 77 tumours from exposed
      persons, we identified 7 ALK rearrangements and none in the unexposed group. When
      combining ALK and RET rearrangements, we found 24 in the exposed (31.2%) compared
      to two (10.5%) in the unexposed group. Odds ratios increased significantly in a
      dose-dependent manner up to 6.2 (95%CI: 1.1, 34.7; p = 0.039) at Iodine-131
      thyroid doses >500 mGy. In total, 27 cases carried point mutations of BRAF or RAS
      genes, yet logistic regression analysis failed to identify significant dose
      association. To our knowledge we are the first to describe ALK rearrangements in
      post-Chernobyl PTC samples using routine methods such as FISH and IHC. Our
      findings further support the hypothesis that gene rearrangements, but not
      oncogenic driver mutations, are associated with ionising radiation-related tumour
      risk. IHC may represent an effective method for ALK-screening in PTCs with known
      radiation aetiology, which is of clinical value since oncogenic ALK activation
      might represent a valuable target for small molecule inhibitors.

PMID- 29633577
TI  - Mutations in COL1A1 Gene Change Dentin Nanostructure: A Response.

PMID- 29633576
TI  - Polarized light microscopy for 3-dimensional mapping of collagen fiber
      architecture in ocular tissues.
AB  - Collagen fibers play a central role in normal eye mechanics and pathology. In
      ocular tissues, collagen fibers exhibit a complex 3-dimensional (3D) fiber
      orientation, with both in-plane (IP) and out-of-plane (OP) orientations. Imaging
      techniques traditionally applied to the study of ocular tissues only quantify IP
      fiber orientation, providing little information on OP fiber orientation. Accurate
      description of the complex 3D fiber microstructures of the eye requires
      quantifying full 3D fiber orientation. Herein, we present 3dPLM, a technique
      based on polarized light microscopy developed to quantify both IP and OP collagen
      fiber orientations of ocular tissues. The performance of 3dPLM was examined by
      simulation and experimental verification and validation. The experiments
      demonstrated an excellent agreement between extracted and true 3D fiber
      orientation. Both IP and OP fiber orientations can be extracted from the sclera
      and the cornea, providing previously unavailable quantitative 3D measures and
      insight into the tissue microarchitecture. Together, the results demonstrate that
      3dPLM is a powerful imaging technique for the analysis of ocular tissues.

PMID- 29633578
TI  - Label-free bacterial colony detection and viability assessment by continuous-wave
      terahertz transmission imaging.
AB  - Timely and accurate bacterial detection is critical for various health and safety
      applications, which promotes the continuous development of versatile optical
      sensors for bacterial investigations. Here, we report a new strategy for
      bacterial colony sensing using terahertz (THz) imaging with minimal assay
      procedures. The proposed method utilizes the acute sensitivity of THz wave to the
      changes in the water content and cellular structures. Single bacterial colonies
      of 4 bacterial species were directly distinguished using THz imaging by utilizing
      their differences in THz absorption. In addition, the distribution of mixed
      bacterial samples has been demonstrated by THz imaging, which demonstrated that
      the target bacterium could be easily recognized. Furthermore, we investigated the
      differentiation of bacterial viability, which indicated that bacteria under
      different living states could be distinguished by THz imaging because of their
      different hydration levels and cellular structures. Our results suggest that THz
      imaging has the potential to be used for mixed bacterial sample detection and
      bacterial viability assessment in a label-free and nondestructive manner.

PMID- 29633579
TI  - Quality metrics in transplantation - A new emphasis on transplant access.

PMID- 29633580
TI  - Treatment advocate tactics to expand access to antiviral therapy for HIV and
      viral hepatitis C in low- to high-income settings: making sure no one is left
      behind.
AB  - INTRODUCTION: Worldwide, 71 million people are infected with hepatitis C virus
      (HCV), which, without treatment, can lead to liver failure or hepatocellular
      carcinoma. HCV co-infection increases liver- and AIDS-related morbidity and
      mortality among HIV-positive people, despite ART. A 12-week course of HCV direct
      acting antivirals (DAAs) usually cures HCV - regardless of HIV status. However,
      patents and high prices have created access barriers for people living with HCV,
      especially people who inject drugs (PWID). Inadequate access to and coverage of
      harm reduction interventions feed the co-epidemics of HIV and HCV; as a result,
      the highest prevalence of HCV is found among PWID, who face additional obstacles
      to treatment (including stigma, discrimination and other structural barriers).
      The HIV epidemic occurred during globalization of intellectual property rights,
      and highlighted the relationship between patents and the high prices that prevent
      access to medicines. Indian generic manufacturers produced affordable generic HIV
      treatment, enabling global scale-up. Unlike HIV, donors have yet to step forward
      to fund HCV programmes, although DAAs can be mass-produced at a low and
      sustainable cost. Unfortunately, although voluntary licensing agreements between
      originators and generic manufacturers enable low-income (and some lower-middle
      income countries) to buy generic versions of HIV and HCV medicines, most middle
      income countries with large burdens of HCV infection and HIV/HCV co-infection are
      excluded from these agreements. Our commentary presents tactics from the HIV
      experience that treatment advocates can use to expand access to DAAs. DISCUSSION:
      A number of practical actions can help increase access to DAAs, including new
      research and development (R&D) paradigms; compassionate use, named-patient and
      early access programmes; use of TRIPS flexibilities such as compulsory licences
      and patent oppositions; and parallel importation via buyers' clubs. Together,
      these approaches can increase access to antiviral therapy for people living with
      HIV and viral hepatitis in low-, middle- and high-income settings. CONCLUSIONS:
      The HIV example provides helpful parallels for addressing challenges to expanding
      access to HCV DAAs. HCV treatment access - and harm reduction - should be
      massively scaled-up to meet the needs of PWID, and efforts should be made to
      tackle stigma and discrimination, and stop criminalization of drug use and
      possession.

PMID- 29633581
TI  - Persistent socket pain postenucleation and post evisceration: a systematic
      review.
AB  - PURPOSE: To investigate causes, diagnostics and treatment modalities for
      persistent socket pain (PSP) after enucleation and evisceration. METHODS: A
      systematic search was undertaken in accordance with the PRISMA Statement, in
      PubMed, Embase.com and Thomson Reuters/Web of Science. We searched for relevant
      papers until the 28th of July 2016. Inclusion criteria were (1) patients with a
      history of enucleation or evisceration, (2) PSP, (3) report of the cause and/or
      used diagnostics and/or treatment modality, (4) full text in English, Dutch or
      Spanish language. Excluded were (1) review articles, (2) comments, and
      publications concerning, (3) nonhumans, (4) exenterated patients, (5) acute
      postoperative pain, or (6) periorbital pain without pain in the socket. Given the
      lack of high quality evidence from randomized controlled trials, we examined all
      available evidence from primary observational studies and assessed quality within
      this lower level of evidence. RESULTS: A total of 32 studies were included.
      Causes of PSP found were prosthesis-related (n = 5), dry socket (n = 2),
      trochleitis (n = 3), compression of the trigeminal nerve (n = 2), implant-related
      (n = unknown), inflammation (n = 5), surgery-related (n = 4), neuromas (n = 8),
      malignant tumours (n = 3), psychiatric/psychosocial (n = 2), phantom pain (n =
      149), rarer entities (n = 3) or unknown (n = 14). Nonsurgical treatments suffice
      for conditions as trochleitis, prosthesis-related pain, dry socket and for
      phantom pain. Other causes of pain may require more invasive treatments such as
      implant removal. CONCLUSION: Careful history and examination can give some
      direction in the diagnostic procedure; however, PSP is probably multifactorial
      and the specific origin(s) may remain uncertain. Implant replacement can be an
      effective treatment. Studies to identifiy less invasive procedures are required.

PMID- 29633582
TI  - Polyurethane/polyurethane nanoparticle-modified expanded
      poly(tetrafluoroethylene) vascular patches promote endothelialization.
AB  - Expanded poly(tetrafluoroethylene) (ePTFE) has been widely used as a vascular
      graft material due to the fact that it is durable, porous, flexible, and inert.
      However, ePTFE grafts easily induce thrombosis, calcification and neointimal
      hyperplasia in small-diameter (<6 mm) graft bypass surgeries and thus cause
      surgical failure. Therefore, it is necessary to improve the in vitro and in vivo
      performances of ePTFE grafts. In this work, we first prepared a
      polyurethane/polyurethane nanoparticles (PU/PU-NPs) composite film by a simple
      cosedimentation method. Compared with the pure PU film, the blood compatibility
      and the cell compatibility of the PU/PU-NPs composite film were significantly
      improved. Then, we constructed a PU/PU-NPs/ePTFE vascular patch (PPVP) by coating
      PU and PU-NPs onto the surface of an ePTFE graft. PU-NP modification endowed the
      ePTFE graft with the nanopatterned surface similar to the luminal surface of a
      blood vessel. PU NPs and the structural likeness of the surface synergistically
      optimized the overall performance, and thus improved the blood and cell
      compatibilities, effectively inhibited platelet adhesion, enhanced cell
      attachment and proliferation, and facilitated the formation of endothelial tissue
      endothelialization. The abdominal artery patched with PPVP was not blocked and
      the endothelialization was achieved 30 days after the implantation. All the
      results taken together indicate that PPVP may be a promising alternative for a
      vascular patch. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A:
      2131-2140, 2018.

PMID- 29633583
TI  - Pattern of Daily Steps is Associated with Weight Loss: Secondary Analysis from
      the Step-Up Randomized Trial.
AB  - OBJECTIVE: The aim of this study was to examine the association between the
      amount, intensity, and pattern of steps.day-1 with weight loss. METHODS:
      Participants (N = 260; age = 42.8 +/- 8.9 y; BMI = 32.8 +/- 3.5 kg/m2 ) completed
      an 18-month weight-loss intervention that included a calorie-restricted diet and
      prescribed physical activity. Participants were categorized by 18-month weight
      loss as weight gain (GAIN), weight loss of 0% to < 5% (WL < 5%), 5% to < 10% (WL
      < 10%), or >= 10% (WL >= 10%). Steps.day-1 were measured at 0, 6, 12, and 18
      months and defined as total steps.day-1 , total steps.day-1 of moderate-to
      vigorous physical activity (MVPA) (>=3 metabolic equivalents) in bouts of >= 10
      minutes (BOUT-MVPA), MVPA in bouts of < 10 minutes (NON-BOUT-MVPA), or non-MVPA
      steps.day-1 (NON-MVPA). RESULTS: There was a weight-loss category by time
      interaction (P < 0.0001) for total and BOUT-MVPA steps.day-1 . The total
      steps.day-1 at 18 months were WL >= 10% = 9,822 (95% CI: 9,073-10,571), WL < 10%
      = 8,612 (7,613-9,610), WL < 5% = 7,802 (6,782-8,822), and GAIN = 7,801 (6,549
      9,053). BOUT-MVPA steps.day-1 at 18 months were WL >= 10% = 3,482 (2,982-3,981),
      WL < 10% = 1,949 (1,269-2,629), WL < 5% = 1,735 (1,045-2,426), and GAIN = 1,075
      (210-1,941). Participants were also categorized based on achieving >= 10% weight
      loss at either 6 or 18 months, and a similar pattern was observed. CONCLUSIONS:
      These findings show that 10,000 steps.day-1 , with approximately 3,500 steps.day
      1 performed as BOUT-MVPA, are associated with enhanced weight loss in a
      behavioral intervention.

PMID- 29633584
TI  - Virtual Fragment Screening Identification of a Quinoline-5,8-dicarboxylic Acid
      Derivative as a Selective JMJD3 Inhibitor.
AB  - The quinoline-5,8 dicarboxylic acid scaffold has been identified by a fragment
      based approach as new potential lead compound for the development of JMJD3
      inhibitors. Among them, 3-(2,4-dimethoxypyrimidin-5-yl)quinoline-5,8-dicarboxylic
      acid (compound 3) shows low micromolar inhibitory activity against Jumonji domain
      containing protein 3 (JMJD3). The experimental evaluation of inhibitory activity
      against seven related isoforms of JMJD3 highlighted an unprecedented selectivity
      toward the biological target of interest.

PMID- 29633585
TI  - A multiobjective optimization procedure for the electrode design of cochlear
      implants.
AB  - This paper presents a new procedure to design optimal electrodes for cochlear
      implants. The main objective of this study is to find a set of electrode designs
      that maximize the focalization and minimize the power consumption simultaneously.
      To achieve that, a criterion to measure the ability of focalization of an
      electrode is proposed. It is presented a procedure to determine (1) the
      electrical potential induced by an electrode by solving the Laplace equation
      through the finite element method; (2) the response of a neuron to an applied
      field using NEURON, a compartmentalized cell model; (3) the optimization to find
      the best electrode designs according to power consumption and focalization by 2
      evolutionary multiobjective methods based on the non-dominated sorting genetic
      algorithm II: a straight multiobjective approach and a seeded multiobjective
      approach. An electrode design formed by 2 conductive rings with a possible
      difference of potential between them is proposed. It is analyzed that the
      response of the neuron is determined by the shape and the difference of the
      potential between the electrode rings. Our procedure successfully achieves a
      nondominated set of optimum electrode designs improving a standard electrode in
      both objectives, as designs with better focalization allow to include extra
      electrodes in the cochlear implant, and designs with lower power consumption
      extend the length of the battery.

PMID- 29633586
TI  - Congenital X-Linked Retinoschisis: An Updated Clinical Review.
AB  - We present an updated clinical review of the pathophysiology, progression, and
      current treatments in pediatric patients with congenital X-linked retinoschisis
      (CXLRS). CXLRS is an X-linked inherited retinal degeneration characterized by
      splitting of the superficial layers of the retina. Most recent classification
      divides CXLRS into 4 distinct clinical phenotypes: type 1, foveal; type 2,
      foveolamellar; type 3, complex; and type 4, foveoperipheral. The majority of
      retinoschisis cavities remain stable throughout life and may spontaneously
      collapse. However, a select number of patients progress to macula-involving
      peripheral retinoschisis, rhegmatogenous, and combined tractional-rhegmatogenous
      detachments that require further intervention. Although several advances have
      been made over the past several decades, medical therapy remains limited to case
      series-based carbonic anhydrase therapy and prophylactic laser retinopexy. Recent
      advances in genetic-based clinical trials with the retinoschisis gene are
      promising. Vitreoretinal surgical approaches remain complex, case-based, and
      require careful planning depending on the configuration and location of the
      retinoschisis cavity.

PMID- 29633587
TI  - Anti-VEGF for ROP and Pediatric Retinal Diseases.
AB  - Vascular endothelial growth factor (VEGF) is an important mediator of the
      pathological neovascularization and vascular permeability of the eye. The
      increasing use of intravitreal therapies targeting VEGF has revolutionized the
      treatment of pediatric vitreoretinal diseases. In retinopathy of prematurity
      (ROP), the role of VEGF in pathogenesis has been well recognized and the use of
      anti-VEGF treatment in phase 2 ROP has demonstrated promising results,
      particularly in severe cases of posterior disease. This has made VEGF an
      established target in the treatment of pediatric retinal diseases known to have
      abnormal vascular activity. However, questions remain about late systemic and
      neurodevelopmental effects after anti-VEGF therapy for children because
      intravitreal injection of anti-VEGF may result in systemic circulation of anti
      VEGF agent and a corresponding suppression of systemic VEGF. We do not currently
      know whether the short-term suppression of systemic VEGF affects long-term
      neurodevelopmental outcomes because VEGF is a vital supporting factor during
      neurodevelopment. This review article focuses on the evidence for the use of anti
      VEGF treatment in certain pediatric ocular diseases, including ROP, Coats
      disease, and retinoblastoma. More extensive and prospective studies are warranted
      to further elucidate the role of anti-VEGF therapy in these diseases and
      illustrate how we can optimally use these agents in pediatric patients.

PMID- 29633588
TI  - Familial Exudative Vitreoretinopathy: Pathophysiology, Diagnosis, and Management.
AB  - Familial exudative vitreoretinopathy (FEVR) is a heritable vitreoretinopathy
      characterized by anomalous retinal vascular development. The principal feature of
      the disease is an avascular peripheral retina. This in turn can cause further
      pathological changes including neovascularization, exudation, hemorrhage, and
      retinal detachment. The biological basis of the disease is thought to be from
      defects in the Wnt signaling pathway. Many gene mutations have been implicated,
      and these can be inherited in an autosomal dominant (most common), autosomal
      recessive, and X-linked recessive fashion. Examination with wide-field
      fluorescein angiography is essential and can identify the disease in its earlier
      stages, enabling timely treatment, in addition to helping identify asymptomatic
      family members. The current treatment paradigm involves laser photocoagulation of
      the avascular peripheral retina for neovascular sequelae and vitreoretinal
      surgery for progressive retinal detachment. Further studies are underway to
      better characterize this complex vitreoretinopathy.

PMID- 29633589
TI  - Skeletal Muscle CLARITY: A Preliminary Study of Imaging The Three-Dimensional
      Architecture of Blood Vessels and Neurons.
AB  - OBJECTIVES: Passive CLARITY is a whole-tissue clearing protocol, based on sodium
      dodecyl sulfate (SDS) clearing, for imaging intact tissue containing transgenic
      or immunolabeled fluorescent proteins. In this study, we present an improved
      passive CLARITY protocol with efficient immunolabeling without the need for
      electrophoresis or complex instrumentation. MATERIALS AND METHODS: In this
      experimental study, after perfusion of C57BL/6N mice with phosphate-buffered
      saline (PBS) and then with acrylamide-paraformaldehyde (PFA), the quadriceps
      femoris muscle was removed. The muscle samples were post-fixed and degassed to
      initiate polymerization. After removing the excess hydrogel around the muscle,
      lipids were washed out with the passive CLARITY technique. The transparent whole
      intact muscles were labeled for vessel and neuron markers, and then imaged by
      confocal microscopy. Three-dimensional images were reconstructed to present the
      muscle tissue architecture. RESULTS: We established a simple clearing protocol
      using wild type mouse muscle and labeling of vasculatures and neurons. Imaging
      the fluorescent signal was achieved by protein fixation, adjusting the pH of the
      SDS solution and using an optimum temperature (37C) for tissue clearing, all of
      which contributed to the superiority of our protocol. CONCLUSIONS: We conclude
      that this passive CLARITY protocol can be successfully applied to three
      dimensional cellular and whole muscle imaging in mice, and will facilitate
      structural analyses and connectomics of large assemblies of muscle cells, vessels
      and neurons in the context of three-dimensional systems.

PMID- 29633590
TI  - Testosterone Reduces Spinal Cord Injury-Induced Effects on Male Reproduction by
      Preventing CADM1 Defect.
AB  - OBJECTIVES: This study evaluated the effects of exogenous testosterone molecule-1
      (CADM1) pathological defect during early and chronic periods of spinal cord
      injury (SCI). MATERIALS AND METHODS: In this experimental study, Testosterone was
      administered immediately or after one week of SCI induction. Along with
      quantification of CADM1 gene expression and its immunoreactivity, we evaluated
      sperm parameters and serum testosterone level post-SCI. RESULTS: Different grades
      of abnormalities in sperm parameters and testis architecture were observed along
      with significant reductions in the level of CADM1 expression and its
      immunoreactivity in the seminiferous tubules of both acute and chronic SCI
      groups. Exogenous testosterone, by compensating the serum testosterone level.
      reduced the percentage of apoptotic and both short head and abnormal sperm froms
      in the caudal epididymis. Importantly, the beneficial effects of immediate
      administration of testosterone were prominent. Increases in the level of CADM1
      transcription and its immunoreactivity in the testis of SCI mice treated with
      testosterone were accompanied by improvement of sperm motility as well as
      testicular Johnsen's and Miller's criteria. CONCLUSIONS: Since immediate
      testosterone treatment improved the immunoreactivity and transcription level of
      CADM1, the observed beneficial effect of exogenouse testosterone can be
      attributed to its effect on CADM1 dynamics.

PMID- 29633591
TI  - Targetome Analysis Revealed Involvement of MiR-126 in Neurotrophin Signaling
      Pathway: A Possible Role in Prevention of Glioma Development.
AB  - OBJECTIVES: For the first time, we used molecular signaling pathway enrichment
      analysis to determine possible involvement of miR-126 and IRS-1 in neurotrophin
      pathway. MATERIALS AND METHODS: In this prospective study, Validated and
      predicted targets (targetome) of miR-126 were collected following searching
      miRtarbase (http://mirtarbase.mbc.nctu.edu.tw/) and miRWalk 2.0 databases,
      respectively. Then, approximate expression of miR-126 targeting in Glioma tissue
      was examined using UniGene database (http://www.ncbi. nlm.nih.gov/unigene). In
      silico molecular pathway enrichment analysis was carried out by DAVID 6.7
      database (http://david. abcc.ncifcrf.gov/) to explore which signaling pathway is
      related to miR-126 targeting and how miR-126 attributes to glioma development.
      RESULTS: MiR-126 exerts a variety of functions in cancer pathogenesis via
      suppression of expression of target gene including PI3K, KRAS, EGFL7, IRS-1 and
      VEGF. Our bioinformatic studies implementing DAVID database, showed the
      involvement of miR-126 target genes in several signaling pathways including
      cancer pathogenesis, neurotrophin functions, Glioma formation, insulin function,
      focal adhesion production, chemokine synthesis and secretion and regulation of
      the actin cytoskeleton. CONCLUSIONS: Taken together, we concluded that miR-126
      enhances the formation of glioma cancer stem cell probably via down regulation of
      IRS-1 in neurotrophin signaling pathway.

PMID- 29633592
TI  - The Effects of De-Whiskering and Congenital Hypothyroidism on The Development of
      Nitrergic Neurons in Rat Primary Somatosensory and Motor Cortices.
AB  - OBJECTIVES: The aim of the present study is to investigate the effects of chronic
      whisker deprivation on possible alterations to the development of nitrergic
      neurons in the whisker part of the somatosensory (wS1) and motor (wM1) cortices
      in offspring with congenital hypothyroidism (CH). MATERIALS AND METHODS: In the
      experimental study, CH was induced by adding propylthiouracil to the rats
      drinking water from embryonic day 16 to postnatal day (PND) 60. In whisker
      deprived (WD) pups, all the whiskers were trimmed from PND 1 to 60. Nitrergic
      interneurons in the wS1/M1 cortices were detected by NADPH-diaphorase
      histochemistry staining technique in the control (Ctl), Ctl+WD, Hypo and Hypo+WD
      groups. RESULTS: In both wS1 and wM1 cortices the number of nitrergic neurons was
      significantly reduced in the Hypo and Hypo+WD groups compared to Ctl and Ctl+WD
      groups, respectively (P<0.05) while bilateral whisker deprivation had no
      remarkable effect. The mean soma diameter size of NADPH-d labeled neurons in the
      Ctl+WD and Hypo+WD groups was decreased compared to the Ctl and Hypo groups,
      respectively. A similar patterns of decreased NADPH-d labeled neurons in the
      wS1/M1 cortices occur in the processes of nitrergic neurons in both congenital
      hypothyroidism and whisker deprivation. CONCLUSIONS: Our results suggest that
      both congenital hypothyroidism and whisker deprivation may disturb normal
      development of the wS1 and wM1 cortical circuits in which nitrergic neurons are
      involved.

PMID- 29633593
TI  - Differentiation of Human Scalp Adipose-Derived Mesenchymal Stem Cells into Mature
      Neural Cells on Electrospun Nanofibrous Scaffolds for Nerve Tissue Engineering
      Applications.
AB  - OBJECTIVES: This study aimed to isolate and culture SADS cells, investigate their
      neurogenic capacity and evaluate their application for nerve tissue engineering.
      MATERIALS AND METHODS: In this experimental study, SADS cells were isolated from
      human adipose tissue. After 7-day treatment of SADS cells with insulin,
      indomethacin and isobutylmethylxanthine, neurogenic differentiation of SADS cells
      was investigated. During this study, Poly (epsilon-caprolactone) (PCL) and
      PCL/gelatin nanofibrous scaffolds were fabricated using electrospinning and
      subsequently nanofibrous scaffolds were coated with platelet-rich plasma (PRP).
      SADS cells were also seeded on nanofibrous scaffolds and neurogentic
      differentiation of these cells on nanofibers was also evaluated. Effect of PRP on
      proliferation and differentiation of SADS cells on scaffolds was also studied.
      RESULTS: Our results showed that after 7-day treatment of SADS cells with
      insulin, indomethacin and isobutylmethylxanthine, SADS cells expressed markers
      characteristic of neural cells such as nestin and neuron specific nuclear protein
      (NEUN) (as early neuronal markers) as well as microtubule-associated protein 2
      (MAP2) and neuronal microtubule-associated (TAU) (as mature neuronal markers)
      while mature astrocyte maker (GFAP) was not expressed. MTT assay and SEM results
      showed that incorporation of gelatin and PRP into the structure of nanofibrous
      scaffolds has a significant positive influence on the bioactivity of scaffolds.
      Our results also showed neurogentic differentiation of SADS cells on scaffolds.
      CONCLUSIONS: Our results demonstrated that SADS cells have potential to
      differentiate into early and mature progenitor neurons, in vitro. PCL/gelatin/PRP
      was found to be a promising substrate for proliferation of SADS cells and
      differentiation of these cells into neural cells which make these scaffolds a
      candidate for further in vivo experiments and suggest their application for nerve
      tissue engineering.

PMID- 29633594
TI  - OX40 Gene and Serum Protein Expression Profiles in Patients with Parkinson's
      Disease.
AB  - OBJECTIVES: Inflammation of the immune system and the central nervous system has
      been known as an important predisposing factor for Parkinson's disease (PD).
      Increased expression of OX40 protein (CD134) is a known factor for increased
      inflammation and initiation of NF-kappa-B signaling pathway in different
      diseases. We aimed to investigate the expression of OX40 at the transcript and
      serum protein levels. MATERIALS AND METHODS: Twenty individuals with PD and 20
      healthy individuals, as controls, were enrolled in this casecontrol study.
      Expression of OX40 at the transcript level and serum protein levels were measured
      by quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked
      immunosorbent assays respectively. RESULTS: The mean expression level of OX40 was
      increased in patients but not at a significant level (P>0.05). Consistently, the
      mean serum concentration of OX40 showed a mild, but non-significant, increase in
      the patients (P>0.05). CONCLUSIONS: We conclude that OX40 expression at either
      the transcript or protein level has no diagnostic utility in asymptomatic PD.
      This shows the need for clinical, cellular and interventional research to detect
      new robust biomarkers.

PMID- 29633595
TI  - Ghrelin Upregulates Hoxb4 Gene Expression in Rat Bone Marrow Stromal Cells.
AB  - OBJECTIVES: Ghrelin is a peptide which has a proliferative and antiapoptotic
      effect in many cells including bone marrow stromal cells (BMSCs). Homeobox
      protein B4 (HOXB4) is a transcription factor involved in stem cell regeneration
      and survival. The aim of the study was to find out the efect of ghrelin on Hoxb4
      expression in BMSCs. MATERIALS AND METHODS: In this experimental study, rat BMSCs
      were cultivated in Dulbecco's Modified Eagle Medium (DMEM). Passage three BMSCs
      were treated with ghrelin 100 MUM for 48 hours. Real-time polymerase chain
      reaction (PCR) was carried out from the untreated BMSCs (B), BMSCs treated with
      125 MUM H2O2 (BH), BMSCs treated with 100 MUM ghrelin then 125 MUM H2O2 (BGH) and
      BMSCs treated with 100 MUM ghrelin (BG) groups. For immunofluorescence, cells
      were incubated with an anti-HOXB4 monoclonal antibody. Primary antibodies were
      visualized using the Fluorescein isothiocyanate (FITC) method. All data are
      presented as mean +/- SEM and P<0.05 was considered as statistical significant.
      RESULTS: Hoxb4 expression significantly increased in the BG compared with BH and
      BGH groups. Furthermore, 100 MUM ghrelin, increased the mean of HOXB4 positive
      immunoreactive cells compared to the BH group. CONCLUSIONS: Ghrelin probably
      enhances proliferation and viability of BMSCs through Hoxb4 upregulation.
      However, the signaling pathway and other biological outcomes of this effect
      should be elucidated in different stem cells.

PMID- 29633596
TI  - Promoter Methylation Status of Survival-Related Genes in MOLT- 4 Cells Co
      Cultured with Bone Marrow Mesenchymal Stem Cells under Hypoxic Conditions.
AB  - OBJECTIVES: DNA methylation is a well-studied epigenetic mechanism that is a
      potent arm of the gene expression controlling machinery. Since the hypoxic
      situation and the various cells of bone marrow microenvironment, e.g. mesenchymal
      stem cells, play a role in the in vivo and in vitro biology of leukemic cells, we
      decided to study the effects of hypoxia and mesenchymal stem cells (MSCs) on the
      promoter methylation pattern of BAX and BCL2 genes. MATERIALS AND METHODS: In
      this experimental study, the co-culture of MOLT-4 cells with MSCs and treatment
      with CoCl2 was done during 6, 12, and 24 hour periods. Total DNA was extracted
      using commercial DNA extraction kits, and sodium bisulfite (SBS) treatment was
      performed on the extracted DNA. Methylation specific polymerase chain reaction
      (MSP) was used to evaluate the methylation status of the selected genes' promoter
      regions. RESULTS: The BAX and BCL2 promoters of untreated MOLT-4 cells were in
      partial methylated and fully unmethylated states, respectively. After incubating
      the cancer cells with CoCl2 and MSCs, the MSP results after 6, 12, and 24 hours
      were the same as untreated MOLT-4 cells. In other words, the exposure of MOLT-4
      cells to the hypoxia-mimicry agent and MSCs in various modes and different time
      frames showed that these factors have exerted no change on the methylation
      signature of the studied fragments from the promoter region of the mentioned
      genes. CONCLUSIONS: Hypoxia and MSCs actually have no notable effect on the
      methylation status of the promoters of BAX and BCL2 in the specifically studied
      regions. DNA methylation is probably not the main process by which MSCs and CoCl2
      induced hypoxia regulate the expression of these genes. Finally, we are still far
      from discovering the exact functional mechanisms of gene expression directors,
      but these investigations can provide new insights into this field for upcoming
      studies.

PMID- 29633597
TI  - MicroRNA Microarray Profiling during Megakaryocyte Differentiation of Cord Blood
      CD133+ Hematopoietic Stem Cells.
AB  - OBJECTIVES: In order to clarify the role of microRNAs (miRNA) in megakaryocyte
      differentiation, we ran a microRNA microarray experiment to measure the
      expression level of 961 human miRNA in megakaryocytes differentiated from human
      umbilical cord blood CD133+ cells. MATERIALS AND METHODS: In this experimental
      study, human CD133+ hematopoietic stem cells were collected from three human
      umbilical cord blood (UCB) samples, and then differentiated to the megakaryocytic
      lineage and characterized by flow cytometry, CFU-assay and ploidy analysis.
      Subsequently, microarray analysis was undertaken followed by quantitative
      polymerase chain reaction (qPCR) to validate differentially expressed miRNA
      identified in the microarray analysis. RESULTS: A total of 10 and 14 miRNAs were
      upregulated (e.g. miR-1246 and miR-148-a) and down-regulated (e.g. miR- 551b and
      miR-10a) respectively during megakaryocyte differentiation, all of which were
      confirmed by qPCR. Analysis of targets of these miRNA showed that the majority of
      targets are transcription factors involved in megakaryopoiesis. CONCLUSIONS: We
      conclude that miRNA play an important role in megakaryocyte differentiation and
      may be used as targets to change the rate of differentiation and further our
      understanding of the biology of megakaryocyte commitment.

PMID- 29633598
TI  - The Association between PARP1 and LIG3 Expression Levels and Chromosomal
      Translocations in Acute Myeloid Leukemia Patients.
AB  - OBJECTIVES: Chromosomal translocations are among the most common mutational
      events in cancer development, especially in hematologic malignancies. However,
      the precise molecular mechanism of these events is still not clear. It has been
      recently shown that alternative non-homologous end-joining (alt-NHEJ), a newly
      described pathway for double-stranded DNA break repair, mediates the formation of
      chromosomal translocations. Here, we examined the expression levels of the main
      components of alt-NHEJ (PARP1 and LIG3) in acute myeloid leukemia (AML) patients
      and assessed their potential correlation with the formation of chromosomal
      translocations. MATERIALS AND METHODS: This experimental study used reverse
      transcription-quantitative polymerase chain reaction (RTqPCR) to quantify the
      expression levels of PARP1 and LIG3 at the transcript level in AML patients
      (n=78) and healthy individuals (n=19). RESULTS: PARP1 was the only gene
      overexpressed in the AML group when compared with healthy individuals (P=0.0004),
      especially in the poor prognosis sub-group. Both genes were, however, found to be
      up-regulated in AML patients with chromosomal translocations (P=0.04 and 0.0004
      respectively). Moreover, patients with one isolated translocation showed an over
      expression of only LIG3 (P=0.005), whereas those with two or more translocations
      over-expressed both LIG3 (P=0.002) and PARP1 (P=0.02). CONCLUSIONS: The
      significant correlations observed between PARP1 and LIG3 expression and the rate
      of chromosomal translocations in AML patients provides a molecular context for
      further studies to investigate the causality of this association.

PMID- 29633599
TI  - The Protein Extract of Chlorella minutissima Inhibits The Expression of MMP-1,
      MMP-2 and MMP-9 in Cancer Cells through Upregulation of TIMP-3 and Down
      Regulation of c-Jun.
AB  - OBJECTIVES: Considering the bioactivities exhibited by microalgae, the effect of
      protein extract of Chlorella minutissimma (CP extract) was investigated on the
      expression of human matrix metalloproteinases-1 (MMP-1) in the breast cancer cell
      line MDA-MB231, and that of MMP-2 and -9 in hepatocellular cancer cell line HepG2
      at different expression levels. The study aimed identification and analysis of
      inhibitory activity of microalgal components extracted from Chlorella minutissima
      against human MMPs. MATERIALS AND METHODS: In this experimental study, we
      analysed the effect of Chlorella extracts on MMP-1, -2, and -9 expression at
      various levels. Gelatin zymography was performed to study the inhibitory effect
      of Chlorella exracts on human gelatinases at the activity level, followed by
      western blotting to analyse the expression of all three MMPs at the protein
      level. The similar effect at the mRNA level along with the probable mechanism
      underlying inhibition of MMPs was assessed using real-time polymerase chain
      reaction (PCR). RESULTS: The results reveal that the treatment with CP extract
      decreased the mRNA expression of MMP-1, MMP-2, and MMP-9 by 0.26-, 0.29-, and
      0.40-fold, respectively, at 20 MUg/ml concentration as well as inhibited the
      activity of MMP-2 and MMP-9 by 37.56 and 42.64%, respectively, at 15 MUg/ml
      concentration. Additionally, upregulated mRNA expression of tissue inhibitor of
      metalloproteinases-3 (TIMP-3) by 1.68-fold was seen in HepG2 cells at 20 MUg/ml
      concentration treatment group. However, CP extract did not induce any change in
      the mRNA expression of the TIMP-1, -2 and -4 in HepG2 and TIMP-1, -2, -3 and -4
      in MDA-MB231 cells. Activator protein-1 (AP-1)-dependent c-Jun-mediated
      transcriptional regulation of MMP-1, -2, and -9 was also studied to elucidate the
      appropriate mechanism involved in the inhibition of MMPs. CONCLUSIONS: The CP
      extract successfully inhibited MMP-1, -2, and -9 at different expression levels
      through TIMP-3 upregulation and c-Jun downregulation.

PMID- 29633600
TI  - The Role of MicroRNA Signature as Diagnostic Biomarkers in Different Clinical
      Stages of Colorectal Cancer.
AB  - OBJECTIVES: Colorectal cancer (CRC) is one of the most common cancers and a major
      cause of cancer-related death worldwide. The early diagnosis of colorectal tumors
      is one of the most important challenges in cancer management. MicroRNAs (miRNAs)
      have provided new insight into CRC development and have been suggested as
      reliable and stable biomarkers for diagnosis and prognosis. This study's
      objective was to analyze the differential expression of miRNAs at differentstages
      of CRC searching for possible correlation with clinicopathological features to
      examine their potential value as diagnostic biomarkers. MATERIALS AND METHODS: In
      this case-control study, plasma and matched tissue samples were collected from 74
      CRC patients at stage II-IV as well as blood samples from 32 healthy controls.
      After exhaustive study of the current literature, eight miRNAs including miR
      200c, 20a, 21, 31,135b, 133b,145 and let-7g were selected. The expression level
      of the miRNAs was assayed by quantitative reverse transcriptase-polymerase chain
      reaction (qRT-PCR). Statistical analysis, including t test , Mann-Whitney U,
      Kruskall-Wallis tests and receiver operating characteristic (ROC) curve was
      applied, where needed. RESULTS: Significantly elevated levels of miR-21, miR-31,
      miR-20a, miR-135b, and decreased levels of miR- 200c, miR-145 and let-7 g were
      detected in both plasma and matched tissue samples compared to the healthy group
      (P<0.05). However, no significant differences were observed in the expression
      level of plasma and tissue miR-133b (P>0.05). ROC for tissue miRNAs showed an
      area under the ROC curve (AUC) of 0.98 and P<0.001 for miR-21, 0.91 and P<0.001
      for miR-135b, 0.91 and P<0.001 for miR-31, and 0.92 and P<0.001 for miR-20a.
      CONCLUSIONS: Our results indicate that the expression levels of microRNAs are
      systematically altered in CRC tissue and plasma. In conclusion, detection of miR
      21, miR-135b, miR-31 and miR-20a levels in the tissue might be helpful to
      illuminate the molecular mechanisms underlying CRC carcinogenesis and serve as
      tumor-associated biomarkers for diagnosis.

PMID- 29633601
TI  - Effect of (R)-(+) Pulegone on Ovarian Tissue; Correlation with Expression of
      Aromatase Cyp19 and Ovarian Selected Genes in Mice.
AB  - OBJECTIVES: Pulegone (PGN) is a monoterpene ketone, whose metabolites exert
      several cytotoxic effects in various tissues. The present study was conducted in
      order to evaluate the (R)-(+) PGN-induced alterations in ovarian aromatization,
      proto-oncogenes and estrogen receptoralpha ( ERalpha) and ERbeta receptors
      expressions. MATERIALS AND METHODS: In this experimental study, mature albino
      mice were divided into experimental (received 25 mg/kg, 50 mg/kg and 100 mg/kg
      PGN, orally for 35 days) and control (received 2% solution of Tween 80 as a PGN
      solvent, orally) groups. The mRNA levels of Eralpha, Erbeta, p53, Bcl-2, and
      cytochrome p450 (Cyp19) as well as ovarian angiogenesis were analyzed through
      reverse transcription polymerase chain reaction and immunohistochemical
      techniques, respectively. Moreover, apoptosis of follicular cells, serum estrogen
      and progesterone levels and mRNA damage were investigated via using terminal
      transferase and biotin-16-dUTP staining, electrochemilunescence and fluorescent
      microscopy methods, respectively. RESULTS: The PGN reduced Eralpha, Erbeta and
      Cyp19 expression at 50 mg/kg and 100 mg/kg doses, while significantly elevating
      p53 and reducing Bcl-2 expression. Finally, PGN impaired ovarian angiogenesis,
      increased apoptosis, elevated follicular atresia and reduced serum levels of
      estrogen and progesterone. CONCLUSIONS: Chronic exposure to PGN (50 mg/kg and 100
      mg/kg), severely affects ovarian aromatization, protooncogenes mRNA levels and
      expression of ERs.

PMID- 29633602
TI  - Melatonin Modifies Histone Acetylation During In Vitro Maturation of Mouse
      Oocytes.
AB  - OBJECTIVES: We evaluated the effect of melatonin, as a potent antioxidant agent,
      on glutathione (GSH) and reactive oxygen species (ROS) levels, as well as histone
      H3 lysine 9 (H3K9), and H4 lysine 12 (H4K12) acetylation when added to oocytes
      culture medium. MATERIALS AND METHODS: In this experimental study, two in vitro
      and in vivo groups were used. In the in vitro group, cumulus oocyte complexes
      (COCs) from the ovaries of B6D2F1 mice were cultured in maturation medium
      containing two doses of melatonin (10-9 and 10-6 M) and without melatonin
      [control group treated with dimethyl sulfoxide (DMSO)] for 22-24 hour. The
      cumulus expansion and nuclear status were monitored by an inverted microscope.
      Next, COCs were isolated from the oviducts of superovulated mice and studied as
      the in vivo group. In in vitro and in vivo matured oocytes, GSH and ROS levels
      were assessed by monochlorobimane (MCB) and 2-7-dichlorodihydrofluorescein
      diacetate (H2DCFDA) staining, respectively. Changes in histone acetylation were
      examined by immunofluorescent staining with specific antibodies against
      acetylated H3K9 and H4K12. RESULTS: The H4K12 acetylation and ROS levels were
      significantly higher in the oocytes matured in the in vitro group compared to the
      in vivo group (P<0.05). Furthermore, glutathione levels in the in vitro group
      were considerably lower than that of the in vivo group (P<0.05). Melatonin at the
      concentration of 10-6 M had the most substantial effect on nuclear maturation and
      histone acetylation as well as glutathione and ROS levels in the in vitro group
      (P<0.05). CONCLUSIONS: Exogenous melatonin improves the competence of mouse
      oocytes during in vitro maturation (IVM).

PMID- 29633603
TI  - Advanced Glycation End-Products-, C-Type Lectin- and Cysteinyl/ Leukotriene
      Receptors in Distinct Mesenchymal Stromal Cell Populations: Differential
      Transcriptional Profiles in Response to Inflammation.
AB  - OBJECTIVES: We aimed at characterizing the transcription profiles of
      immunological receptors associated with the biology of mesenchymal stromal cells
      (MSCs). MATERIALS AND METHODS: In this experimental study, quantitative real time
      polymerase chain reaction (qRTPCR) was performed to establish the transcription
      profiles of advanced glycation end-products (RAGE) receptor, C-type lectin
      receptors (CLRs, including DECTIN-1, DECTIN-2 and MINCLE), leukotriene B4 (LTB4)
      receptors (BLT1 and BLT2) and cysteinyl leukotrienes (CysLTs) receptors (CYSLTR1
      and CYSLTR2) in distinct populations of MSCs grown under basic or inflammatory
      conditions. RESULTS: MSCs derived from adipose tissue (AT), foreskin (FSK),
      Wharton's jelly (WJ) and bone marrow (BM) exhibited significantly different
      transcription levels for these genes. Interestingly, these transcription profiles
      substantially changed following exposure of MSCs to inflammatory signals.
      CONCLUSIONS: Collectively, for the first time, our data highlights that MSCs
      depending on their tissue-source, present several relevant receptors potentially
      involved in the regulation of inflammatory and immunological responses.
      Understanding the roles of these receptors within MSCs immunobiology will
      incontestably improve the efficiency of utilization of MSCs during cell-based
      therapies.

PMID- 29633604
TI  - Prostaglandin F-2alpha Stimulates The Secretion of Vascular Endothelial Growth
      Factor and Induces Cell Proliferation and Migration of Adipose Tissue Derived
      Mesenchymal Stem Cells.
AB  - OBJECTIVES: Tissue engineering today uses factors that can induce differentiation
      of mesenchymal stem cells (MSCs) into other cell types. However, the problem of
      angiogenesis in this differentiated tissue remains an unresolved area of research
      interest. The aim of this study was to investigate the effects of prostaglandin F
      2alpha (PGF-2alpha) on the expression of vascular endothelial growth factor
      (VEGF) in human adipose tissue derived MSCs. MATERIALS AND METHODS: In this
      experimental research, human adipose tissue was digested using collagenase. The
      isolated MSCs cells were treated with PGF-2alpha (up to 5 MUg/ml) and incubated
      for 96 hours. Cell proliferation, secretion of VEGF and cell migration were
      spontaneously assayed by MTT, BrdU, ELISA, RT-PCR and scratching methods.
      RESULTS: Cell growth at 1.0, 2.5, 5 MUg/ml of PGF-2alpha was not significantly
      reduced compared to control cells, suggesting that these concentrations of PGF
      2alpha are not toxic to cell growth. The results of the BrdU incorporation assay
      indicated that, in comparison to untreated cells, BrdU incorporation was
      respectively 1.08, 1.96, 2.0 and 1.8 fold among cells treated with 0.1, 1.0, 2.5
      and 5.0 MUg/ml of PGF-2alpha. The scratching test also demonstrated a positive
      influence on cell proliferation and migration. Cells treated with 1.0 MUg/ml of
      PGF-2alpha for 12 hours showed the highest relative migration and coverage in
      comparison to untreated cells. Quantitative VEGF ELISA and RTPCR results
      indicated an increase in VEGF expression and secretion in the presence of PGF
      2alpha. The amount of VEGF produced in response to 0.1, 1.0, 2.5 and 5.0 MUg/ml
      of PGF-2alpha was 62.4 +/- 3.2 , 66.3 +/- 3.7, 53.1 +/- 2.6 and 49.0 +/- 2.3
      pg/ml, respectively, compared to the 35.2 +/- 2.1 pg/ml produced by untreated
      cells. CONCLUSIONS: Stimulation of VEGF secretion by PGF-2alpha treated MSCs
      could be useful for the induction of angiogenesis in tissue engineering in vitro.

PMID- 29633606
TI  - Protective Effect of Aloe vera Extract against Bisphenol A Induced Testicular
      Toxicity in Wistar Rats.
AB  - OBJECTIVES: Bisphenol A (BPA), an endocrine-disrupting chemical, has been
      considered as a possible risk factor for fertility because it induces testicular
      toxicity. Thus, we sought to analyze the effect of Aloe vera as plant with
      antioxidant properties on tissues and oxidative stress parameters in male rats.
      MATERIALS AND METHODS: In this experimental study, 50 adult male Wistar rats (200
      +/- 20 g) have been used in this 56 day study. Animals were completely randomized
      and divided into five groups: A1 (control), A2 (vehicle control), A3 (Aloe vera
      gel 300 mg/kg), B1 (BPA 20 MUg/kg bw) and B2 (Aloe vera gel+ BPA). At the end of
      the study, the rats were anesthetized and 2 ml blood samples were obtained for
      evaluation of oxidative stress markers. Also, both testes were collected for
      histological examinations. RESULTS: BPA significantly decreased (P<0.05) body and
      testis weights. Seminiferous tubule diameter (STD) and height of seminiferous
      epithelium (HSE), were significantly decreased (P<0.05) in the groups receiving
      BPA as compared to the control. There was also a reduction in the quantity of
      spermatocyte and spermatids. Moreover, malondialdehyde (MDA) increased and thiol
      protein (G-SH) decreased. But, co-administration of Aloe vera with BPA
      accelerated the total antioxidant capacity and testicular tissue structure
      healing. CONCLUSIONS: According to our findings, Aloe vera gel extract can
      overcome the damaging effects of BPA on the reproductive system of rats and
      protects rats' testes against BPA-induced toxicity.

PMID- 29633605
TI  - COMPARE CPM-RMI Trial: Intramyocardial Transplantation of Autologous Bone Marrow
      Derived CD133+ Cells and MNCs during CABG in Patients with Recent MI: A Phase
      II/III, Multicenter, Placebo-Controlled, Randomized, Double-Blind Clinical Trial.
AB  - OBJECTIVES: The regenerative potential of bone marrow-derived mononuclear cells
      (MNCs) and CD133+ stem cells in the heart varies in terms of their pro-angiogenic
      effects. This phase II/III, multicenter and double-blind trial is designed to
      compare the functional effects of intramyocardial autologous transplantation of
      both cell types and placebo in patients with recent myocardial infarction (RMI)
      post-coronary artery bypass graft. MATERIALS AND METHODS: This was a phase
      II/III, randomized, double-blind, placebo-controlled trial COMPARE CPM-RMI
      (CD133, Placebo, MNCs - recent myocardial infarction) conducted in accordance
      with the Declaration of Helsinki that assessed the safety and efficacy of CD133
      and MNCs compared to placebo in patients with RMI. We randomly assigned 77
      eligible RMI patients selected from 5 hospitals to receive CD133+ cells, MNC, or
      a placebo. Patients underwent gated single photon emission computed tomography
      assessments at 6 and 18 months post-intramyocardial transplantation. We tested
      the normally distributed efficacy outcomes with a mixed analysis of variance
      model that used the entire data set of baseline and between-group comparisons as
      well as within subject (time) and group*time interaction terms. RESULTS: There
      were no related serious adverse events reported. The intramyocardial
      transplantation of both cell types increased left ventricular ejection fraction
      by 9% [95% confidence intervals (CI): 2.14% to 15.78%, P=0.01] and improved
      decreased systolic wall thickening by -3.7 (95% CI: -7.07 to -0.42, P=0.03). The
      CD133 group showed significantly decreased non-viable segments by 75% (P=0.001)
      compared to the placebo and 60% (P=0.01) compared to the MNC group. We observed
      this improvement at both the 6- and 18-month time points. CONCLUSIONS:
      Intramyocardial injections of CD133+ cells or MNCs appeared to be safe and
      efficient with superiority of CD133+ cells for patients with RMI. Although the
      sample size precluded a definitive statement about clinical outcomes, these
      results have provided the basis for larger studies to confirm definitive evidence
      about the efficacy of these cell types (Registration Number: NCT01167751).

PMID- 29633607
TI  - Identification of A Novel Compound Heterozygous Mutation in BBS12 in An Iranian
      Family with Bardet-Biedl Syndrome Using Targeted Next Generation Sequencing.
AB  - Bardet-Biedl syndrome (BBS) is a pleiotropic and multisystemic disorder
      characterized by rod-cone dystrophy, polydactyly, learning difficulties, renal
      abnormalities, obesity and hypogonadism. This disorder is genetically
      heterogeneous. Until now, a total of nineteen genes have been identified for BBS
      whose mutations explain more than 80% of diagnosed cases. Recently, the
      development of next generation sequencing (NGS) technology has accelerated
      mutation screening of target genes, resulting in lower cost and less time
      consumption. Here, we screened the most common BBS genes (BBS1-BBS13) using NGS
      in an Iranian family of a proposita displaying symptoms of BBS. Among the 18
      mutations identified in the proposita, one (BBS12 c.56T>G and BBS12 c.1156C>T)
      was novel. This compound heterozygosity was confirmed by Sanger sequencing in the
      proposita and her parents. Although our data were presented as a case report,
      however, we suggest a new probable genetic mechanism other than the conventional
      autosomal recessive inheritance of BBS. Additionally, given that in some Iranian
      provinces, like Khuzestan, consanguineous marriages are common, designing
      mutational panels for genetic diseases is strongly recommended, especially for
      those with an autosomal recessive inheritance pattern.

PMID- 29633608
TI  - Identification of A Novel Missense Mutation in The Norrie Disease Gene: The First
      Molecular Genetic Analysis and Prenatal Diagnosis of Norrie Disease in An Iranian
      Family.
AB  - Norrie disease (ND) is a rare X-linked recessive disorder, which is characterized
      by congenital blindness and, in several cases, accompanied with mental
      retardation and deafness. ND is caused by mutations in NDP, located on the
      proximal short arm of the X chromosome (Xp11.3). The disease has been observed in
      many ethnic groups worldwide, however, no such case has been reported from Iran.
      In this study, we present the molecular analysis of two patients with ND and the
      subsequent prenatal diagnosis. Screening of NDP identified a hemizygous missense
      mutation (p.Ser133Cys) in the affected male siblings of the family. The mother
      was the carrier for the mutation (p.Ser133Cys). In a subsequent chorionic
      amniotic pregnancy, we carried out prenatal diagnosis by sequencing NDP in the
      chorionic villi sample at 11 weeks of gestation. The fetus was carrying the
      mutation and thus unaffected. This is the first mutation report and prenatal
      diagnosis of an Iranian family with ND, and highlights the importance of prenatal
      diagnostic screening of this congenital disorder and relevant genetic counseling.

PMID- 29633609
TI  - Method using in vivo quantitative spectroscopy to guide design and optimization
      of low-cost, compact clinical imaging devices: emulation and evaluation of
      multispectral imaging systems.
AB  - With recent proliferation in compact and/or low-cost clinical multispectral
      imaging approaches and commercially available components, questions remain
      whether they adequately capture the requisite spectral content of their
      applications. We present a method to emulate the spectral range and resolution of
      a variety of multispectral imagers, based on in-vivo data acquired from spatial
      frequency domain spectroscopy (SFDS). This approach simulates spectral responses
      over 400 to 1100 nm. Comparing emulated data with full SFDS spectra of in-vivo
      tissue affords the opportunity to evaluate whether the sparse spectral content of
      these imagers can (1) account for all sources of optical contrast present
      (completeness) and (2) robustly separate and quantify sources of optical contrast
      (crosstalk). We validate the approach over a range of tissue-simulating phantoms,
      comparing the SFDS-based emulated spectra against measurements from an
      independently characterized multispectral imager. Emulated results match the
      imager across all phantoms (<3  %   absorption, <1  %   reduced scattering). In
      vivo test cases (burn wounds and photoaging) illustrate how SFDS can be used to
      evaluate different multispectral imagers. This approach provides an in-vivo
      measurement method to evaluate the performance of multispectral imagers specific
      to their targeted clinical applications and can assist in the design and
      optimization of new spectral imaging devices.

PMID- 29633611
TI  - Microfluidic Print-to-Synthesis Platform for Efficient Preparation and Screening
      of Combinatorial Peptide Microarrays.
AB  - In this paper, we introduce a novel microfluidic combinatorial synthesis
      platform, referred to as Microfluidic Print-to-Synthesis (MPS), for custom high
      throughput and automated synthesis of a large number of unique peptides in a
      microarray format. The MPS method utilizes standard Fmoc chemistry to link amino
      acids on a polyethylene glycol (PEG)-functionalized microdisc array. The
      resulting peptide microarrays permit rapid screening for interactions with
      molecular targets or live cells, with low nonspecific binding. Such combinatorial
      peptide microarrays can be reliably prepared at a spot size of 200 MUm with 1 mm
      center-to-center distance, dimensions that require only minimal reagent
      consumption (less than 30 nL per spot per coupling reaction). The MPS platform
      has a scalable design for extended multiplexibility, allowing for 12 different
      building blocks and coupling reagents to be dispensed in one microfluidic
      cartridge in the current format, and could be further scaled up. As proof of
      concept for the MPS platform, we designed and constructed a focused tetrapeptide
      library featuring 2560 synthetic peptide sequences, capped at the N-terminus with
      4-[( N'-2-methylphenyl)ureido]phenylacetic acid. We then used live human T
      lymphocyte Jurkat cells as a probe to screen the peptide microarrays for their
      interaction with alpha4beta1 integrin overexpressed and activated on these cells.
      Unlike the one-bead-one-compound approach that requires subsequent decoding of
      positive beads, each spot in the MPS array is spatially addressable. Therefore,
      this platform is an ideal tool for rapid optimization of lead compounds found in
      nature or discovered from diverse combinatorial libraries, using either
      biochemical or cell-based assays.

PMID- 29633610
TI  - Pancreatic cancer cell detection by targeted lipid microbubbles and multiphoton
      imaging.
AB  - Surgical resection of pancreatic cancer represents the only chance of cure and
      long-term survival in this common disease. Unfortunately, determination of a
      cancer-free margin at surgery is based on one or two tiny frozen section
      biopsies, which is far from ideal. Not surprisingly, cancer is usually left
      behind and is responsible for metastatic disease. We demonstrate a method of
      receptor-targeted imaging using peptide ligands, lipid microbubbles, and
      multiphoton microscopy that could lead to a fast and accurate way of examining
      the entire cut surface during surgery. Using a plectin-targeted microbubble, we
      performed a blinded in-vitro study to demonstrate avid binding of targeted
      microbubbles to pancreatic cancer cells but not noncancerous cell lines. Further
      work should lead to a much-needed point-of-care diagnostic test for determining
      clean margins in oncologic surgery.

PMID- 29633612
TI  - Low-Temperature Presynthesized Crystalline Tin Oxide for Efficient Flexible
      Perovskite Solar Cells and Modules.
AB  - Organic-inorganic metal halide perovskite solar cells (PSCs) have been emerging
      as one of the most promising next generation photovoltaic technologies with a
      breakthrough power conversion efficiency (PCE) over 22%. However, aiming for
      commercialization, it still encounters challenges for the large-scale module
      fabrication, especially for flexible devices which have attracted intensive
      attention recently. Low-temperature processed high-performance electron
      transporting layers (ETLs) are still difficult. Herein, we present a facile low
      temperature synthesis of crystalline SnO2 nanocrystals (NCs) as efficient ETLs
      for flexible PSCs including modules. Through thermal and UV-ozone treatments of
      the SnO2 ETLs, the electron transporting resistance of the ETLs and the charge
      recombination at the interface of ETL/perovskite were decreased. Thus, the
      hysteresis-free highly efficient rigid and flexible PSCs were obtained with PCEs
      of 19.20 and 16.47%, respectively. Finally, a 5 * 5 cm2 flexible PSC module with
      a PCE of 12.31% (12.22% for forward scan and 12.40% for reverse scan) was
      fabricated with the optimized perovskite/ETL interface. Thus, employing
      presynthesized SnO2 NCs to fabricate ETLs has showed promising for future
      manufacturing.

PMID- 29633613
TI  - Enhanced Purification Efficiency and Thermal Tolerance of Thermoanaerobacterium
      aotearoense beta-Xylosidase through Aggregation Triggered by Short Peptides.
AB  - To simplify purification and improve heat tolerance of a thermostable beta
      xylosidase (ThXylC), a short ELK16 peptide was attached to its C-terminus, which
      is designated as ThXylC-ELK. Wild-type ThXylC was normally expressed in soluble
      form. However, ThXylC-ELK assembled into aggregates with 98.6% of total beta
      xylosidase activity. After simple centrifugation and buffer washing, the ThXylC
      ELK particles were collected with 92.57% activity recovery and 95% purity,
      respectively. Meanwhile, the wild-type ThXylC recovery yield was less than 55%
      after heat inactivation, affinity and desalting chromatography followed by HRV 3C
      protease cleavage purification. Catalytic efficiency ( Kcat/ Km) was increased
      from 21.31 mM-1 s-1 for ThXylC to 32.19 mM-1 s-1 for ThXylC-ELK accompanied by a
      small increase in Km value. Heat tolerance of ThXylC-ELK at high temperatures was
      also increased. The ELK16 peptide attachment resulted in 6.2-fold increase of
      half-life at 65  degrees C. Released reducing sugars were raised 1.3-fold during
      sugar cane bagasse hydrolysis when ThXylC-ELK was supplemented into the
      combination of XynADeltaSLH and Cellic CTec2.

PMID- 29633614
TI  - MnO2 Motor: A Prospective Cancer-Starving Therapy Promoter.
AB  - Here, a tumor-targeted MnO2 motor nanosystem (designed as MG/HA) was constructed
      by the assembly of glucose oxidase (GOD), manganese dioxide (MnO2), and
      glycoprotein CD44-targeting polymer hyaluronic acid (HA) to elevate cancer
      starving therapy efficacy in solid tumor. Upon the specific uptake of MG/HA by
      CD44 overexpressed cancer cells, GOD catalyzed the oxidation of glucose into
      gluconic acid and hydrogen peroxide (H2O2) accompanying the consumption of oxygen
      (O2). Meanwhile, MnO2 would react with H2O2 and acid to generate O2, which is in
      turn supplied to the glucose-depletion process, running like a loop. As a result,
      MnO2 is displayed as a motor to promote the rate of glucose depletion that
      contributed to the starving therapy. In contrast to G/HA, MG/HA could not only
      achieve effective glucose consumption to depress cancer progression, but also
      alleviate hypoxia and reduce the expression of Glut1 to inhibit the metabolism
      for further restraining the tumor aggressiveness and metastasis. The concept of
      MnO2 motor shows a promising prospect to overcome the restriction of the starving
      therapy.

PMID- 29633615
TI  - Evidence of Enhanced Carrier Collection in Cu(In,Ga)Se2 Grain Boundaries:
      Correlation with Microstructure.
AB  - Solar cells containing a polycrystalline Cu(In,Ga)Se2 absorber outperform the
      ones containing a monocrystalline absorber, showing a record efficiency of 22.9%.
      However, the grain boundaries (GBs) are very often considered to be partly
      responsible for the enhanced recombination activity in the cell and thus cannot
      explain the registered record efficiency. Therefore, in the present work, we
      resolve this conundrum by performing correlative electron beam-induced current
      electron backscatter diffraction investigations on more than 700 grain boundaries
      and demonstrating that 58% of the grain boundaries exhibit an enhanced carrier
      collection compared to the grain interior. Enhanced carrier collection thus
      indicates that GBs are beneficial for the device performance. Moreover, 27% of
      the grain boundaries are neutral and 15% are recombination-active. Correlation
      with microstructure shows that most of the ?3 GBs are neutral, whereas the random
      high-angle grain boundaries are either beneficial or detrimental. Enhanced
      carrier collection observed for a big fraction of high-angle grain boundaries
      supports the "type-inversion" model and hence the downward band bending at GBs.
      The decrease in current collection observed at one of the high-angle grain
      boundaries is explained by Cu being enriched at this GB and hence by the upward
      shift of the valence band maximum.

PMID- 29633616
TI  - In Vitro Model To Assess Arsenic Bioaccessibility and Speciation in Cooked
      Shrimp.
AB  - Shrimp, a popular and readily consumed seafood, contains high concentrations of
      arsenic. However, few studies have focused on whether arsenic in the shrimp could
      be transformed during the cooking process and gastrointestinal digestion. In this
      study, a combined in vitro model [Unified Bioaccessibility Research Group of
      Europe (BARGE) Method-Simulator of Human Intestinal Microbial Ecosystem (UBM
      SHIME)] was used to investigate arsenic bioaccessibility and its speciation in
      raw and cooked shrimps. The results showed that the cooking practices had little
      effect on the arsenic content and speciation. Bioaccessibility of arsenic in raw
      shrimp was at a high level, averaging 76.9 +/- 4.28 and 86.7 +/- 3.74% in gastric
      and small intestinal phases, respectively. Arsenic speciation was stable in all
      of the shrimp digestions, with nontoxic arsenobetaine (AsB) being the dominated
      speciation. The cooking practice significantly increased the bioaccessibility of
      arsenate ( p < 0.05) in shrimp digests, indicating the increase of the potential
      health risks.

PMID- 29633617
TI  - MptriA, an Acetyltransferase Gene Involved in Pigment Biosynthesis in M.
      purpureus YY-1.
AB  - Monascus pigments (Mps) have been used as food colorants for several centuries in
      Asian countries. MptriA is a putative acetyltransferase gene involved in the MPs
      biosynthesis. To analyze the function of MptriA, an MptriA disruption strain
      (Delta MptriA) and a complementation strain (Delta MptriA:: MptriA) were
      successfully obtained In addition to the loss of color, the disruption of MptriA
      had little effect on the phenotypes during growth on four different media. The
      Delta MptriA strain showed decreased pigment and citrinin production during the
      liquid-fermentation process. Transcriptional analysis showed that the expression
      of several genes involved in the synthesis of pigments and citrinin was down
      regulated in Delta MptriA. These results demonstrated that the role of MptriA was
      to transfer an acyl group to the pyranoquinone structure of the polyketide
      chromophore during Monascus pigment biosynthesis and to influence the citrinin
      biosynthesis pathway. This study contributes to the exploration of pigment
      biosynthesis in M. purpureus.

PMID- 29633618
TI  - Self-Healing Phase Change Salogels with Tunable Gelation Temperature.
AB  - Chemically cross-linked polymer matrices have demonstrated strong potential for
      shape stabilization of molten phase change materials (PCM). However, they are not
      designed to be fillable and removable from a heat exchange module for an easy
      replacement with new PCM matrices and lack self-healing capability. Here, a new
      category of shapeable, self-healing gels, "salogels", is introduced. The salogels
      reversibly disassemble in a high-salinity environment of a fluid inorganic PCM
      [lithium nitrate trihydrate (LNH)], at a preprogrammed temperature. LNH was
      employed as a high latent heat PCM and simultaneously as a solvent, which
      supported the formation of a network of polyvinyl alcohol (PVA) chains via
      physical cross-linking through poly(amidoamine) dendrimers of various
      generations. The existence of hydrogen bonding and the importance of low
      hydration state of PVA for the efficient gelation were experimentally confirmed.
      The thermal behavior of PCM salogels was highly reversible and repeatable during
      multiple heating/cooling cycles. Importantly, the gel-sol transition temperature
      could be precisely controlled within a range of temperature above LNH's melting
      point by the choice of dendrimer generation and their concentration. Shape
      stabilization and self-healing properties of the salogels, taken together with
      tunability of their temperature-induced fluidization make these materials
      attractive for thermal energy storage applications that require on-demand removal
      and replacement of used inorganic PCM salt hydrates.

PMID- 29633619
TI  - [Applicability of non-invasive imaging methods in forensic medicine and forensic
      anthropology in particular].
AB  - Massive progress in developing even more precise imaging modalities influenced
      all medical branches including the forensic medicine. In forensic anthropology,
      an inevitable part of forensic medicine itself, the use of all imaging modalities
      becomes even more important. Despite of acquiring more accurate informations
      about the deceased, all of them can be used in the process of identification
      and/or age estimation. X - ray imaging is most commonly used in detecting foreign
      bodies or various pathological changes of the deceased. Computed tomography, on
      the other hand, can be very helpful in the process of identification, whereas
      outcomes of this examination can be used for virtual reconstruction of living
      objects. Magnetic resonance imaging offers new opportunities in detecting
      cardiovascular pathological processes or develompental anomalies. Ultrasonography
      provides promising results in age estimation of living subjects without excessive
      doses of radiation. Processing the latest information sources available, authors
      introduce the application examples of X - ray imaging, computed tomography,
      magnetic resonance imaging and ultrasonography in everyday forensic medicine
      routine, with particular focusing on forensic anthropology.

PMID- 29633620
TI  - [Deaths of people in the mountainous territory of High Tatras].
AB  - Authors Poprad, since the establishment of the Department of Forensic Medicine in
      Poprad in 1991 up to now. As mountainous environment is considered an area above
      the border of Tatranska magistralna (a tourist footpath which leads across the
      High Tatras and partially Western Tatras). The file discusses the causes and
      mechanisms of death and their causal relationships, shows the nationality, age,
      gender or place of death of deceased people, amounts of deaths in the months of
      year and also in the days of week. Some results are shown in the graphs, the
      percentage results are described in a text. Valuable and complete results were
      reached only in cases with describe statistically a group of people who died in
      the mountainous environment of the High and Belianske Tatras for the last 25
      years and who were dissected on the Department of Forensic Medicine in complete
      documentation (and also after autopsy, not every case of death was autopsied). At
      the same time, the authors describe the system of cooperation between the
      Department of Forensic medicine and Pathological Anatomy of Health care
      surveillance Poprad with Mountain rescue components and the Police force of
      Slovak Republic, operating in the territory of the High and Belianske Tatras.
      These components help us to gain information about the case, which are not
      usually known during the first inspection of dead body in a mortuary or at the
      moment of an autopsy (hikers and climbers are often alone in the mountains, so
      their accidents are without witnesses).

PMID- 29633621
TI  - Omega-3 polyunsaturated fatty acids-enriched hen eggs consumption enhances
      microvascular reactivity in young healthy individuals.
AB  - The beneficial effect of omega-3 polyunsaturated fatty acids (PUFA)
      supplementation on the cardiovascular (CV) system is well supported in CV
      patients; however, the effect of the consumption of omega-3 PUFA-enriched
      functional food in healthy individuals is still not fully elucidated. This study
      aimed to determine the effect of the consumption of omega-3 PUFA-enriched hen
      eggs on the microvascular reactivity (primary outcome), blood pressure (BP), and
      serum lipid profile in young healthy individuals. The control group (N = 16) ate
      3 ordinary hen eggs (277 mg of omega-3 PUFAs/day), and the OMEGA-3 group (N = 20)
      ate 3 omega-3 PUFA-enriched eggs containing 259 mg of omega-3 PUFAs/egg daily
      (alpha-linolenic acid (ALA), 167 mg/egg; eicosapentaenoic acid (EPA), 7 mg/egg;
      docosahexaenoic acid (DHA), 84 mg/egg) for 3 weeks (777 mg of omega-3 PUFA/day).
      Postocclusive reactive hyperemia (PORH) in skin microcirculation assessed by
      laser Doppler flowmetry, serum lipid profile, fasting blood glucose, high
      sensitivity C-reactive protein (hsCRP), and arterial BP were measured in all
      subjects before and after the protocol. PORH was significantly enhanced, and
      triglycerides, hsCRP, and BP were significantly decreased in the OMEGA-3 group
      compared with baseline measurements, whereas there was no significant difference
      in the control group after the protocol when compared with baseline. To the best
      of our knowledge, this is the first study to demonstrate that consumption of a
      mixture of omega-3 PUFA (ALA + EPA + DHA), provided via enriched hen eggs,
      elicits changes in the microvascular reactivity, BP, and triglyceride level in
      healthy subjects that are associated with CV benefits, thus suggesting that daily
      consumption of omega-3 PUFA-enriched eggs in healthy individuals may potentially
      contribute to CV risk factor attenuation and disease prevention.

PMID- 29633622
TI  - Next-generation sequencing showing potential leachate influence on bacterial
      communities around a landfill in China.
AB  - The impact of contaminated leachate on groundwater from landfills is well known,
      but the specific effects on bacterial consortia are less well-studied. Bacterial
      communities in a landfill and an urban site located in Suzhou, China, were
      studied using Illumina high-throughput sequencing. A total of 153 944 good
      quality reads were produced and sequences assigned to 6388 operational taxonomic
      units. Bacterial consortia consisted of up to 16 phyla, including Proteobacteria
      (31.9%-94.9% at landfill, 25.1%-43.3% at urban sites), Actinobacteria (0%-28.7%
      at landfill, 9.9%-34.3% at urban sites), Bacteroidetes (1.4%-25.6% at landfill,
      5.6%-7.8% at urban sites), Chloroflexi (0.4%-26.5% at urban sites only), and
      unclassified bacteria. Pseudomonas was the dominant (67%-93%) genus in landfill
      leachate. Arsenic concentrations in landfill raw leachate (RL) (1.11 * 103 MUg/L)
      and fresh leachate (FL2) (1.78 * 103 MUg/L) and mercury concentrations in RL
      (10.9 MUg/L) and FL2 (7.37 MUg/L) exceeded Chinese State Environmental Protection
      Administration standards for leachate in landfills. The Shannon diversity index
      and Chao1 richness estimate showed RL and FL2 lacked richness and diversity when
      compared with other samples. This is consistent with stresses imposed by elevated
      arsenic and mercury and has implications for ecological site remediation by
      bioremediation or natural attenuation.

PMID- 29633623
TI  - Cystamine slows but not inverses the progression of monocrotaline-induced
      pulmonary arterial hypertension in rats.
AB  - Tissue transglutaminase (TG2) plays an important role in pulmonary arterial
      hypertension (PAH). Previous research indicate that TG2 and protein
      serotonylation catalyzed by TG2 are upregulated in PAH. Serotonin transporter
      inhibitor fluoxetine ameliorates PAH via inhibition of protein serotonylation. It
      is still unknown whether PAH is inhibited through direct inhibition of TG2.
      Therefore, the present study aimed to investigate the effects of TG2 inhibitor
      cystamine on monocrotaline-induced PAH in rats. Rats were treated with
      monocrotaline (60 mg.kg-1, i.p.) in combination with or without cystamine (20, 40
      mg.kg-1.day-1, p.o.). The results showed that compared with monocrotaline alone,
      combination of monocrotaline with cystamine (40 mg.kg-1.day-1, p.o.) relieved
      right ventricle hypertrophy, inhibited pulmonary arteriolar remodeling, and
      downregulated protein expression of TG2, phosphorylated protein kinase B (Akt),
      and extracellular regulated protein kinase (ERK) at day 21. However, except for
      TG2 expression, these changes were not significantly inhibited by cystamine at
      day 35. In addition, cystamine dose-dependently enhanced the survival rate of
      rats injected with monocrotaline at day 35. The findings suggest that cystamine
      slows but not reverses monocrotaline-induced PAH in rats, which was largely
      associated with the inhibition of TG2 protein expression and Akt and ERK
      activation.

PMID- 29633624
TI  - Imidazolines increase the levels of the autophagosomal marker LC3-II in
      macrophage-like RAW264.7 cells.
AB  - This study evaluated whether imidazolines can induce autophagy in the murine
      macrophage-like cell line RAW264.7. Idazoxan increased the content of LC3-II, an
      autophagosomal marker, in RAW264.7 cells. To determine whether this effect was
      due to the induction of its synthesis or inhibition of its degradation, idazoxan
      treatment was performed in the presence of bafilomycin A1, which blocks
      autophagosome-lysosome fusion, as well as Pepstatin A and E-64d, both of which
      block protein degradation in autolysosomes. An increased content of LC3-II was
      observed in the presence of bafilomycin A1 as well as the protease inhibitors.
      Furthermore, an increased number of autophagosomes was observed following
      idazoxan treatment using an autophagosome-specific dye. This indicated that
      idazoxan induced autophagy. Other imidazolines, such as efaroxan, clonidine, and
      2-(2-benzofuranyl)-2-imidazoline, also increased the LC3-II content in RAW264.7
      cells in the presence of bafilomycin A1. Taken together, these results indicate
      that some imidazolines, including idazoxan, can induce autophagy in RAW264.7
      cells.

PMID- 29633625
TI  - Abundance of the arbuscular mycorrhizal fungal taxa associated with the roots and
      rhizosphere soil of different durum wheat cultivars in the Canadian prairies.
AB  - Understanding the variation in how wheat genotypes shape their arbuscular
      mycorrhizal (AM) fungal communities in a prairie environment is foundational to
      breeding for enhanced AM fungi-wheat interactions. The AM fungal communities
      associated with 32 durum wheat genotypes were described by pyrosequencing of
      amplicons. The experiment was set up at two locations in the Canadian prairies.
      The intensively managed site was highly dominated by Funneliformis. Genotype
      influenced the AM fungal community in the rhizosphere soil, but there was no
      evidence of a differential genotype effect on the AM fungal community of durum
      wheat roots. The influence of durum wheat genotype on the AM fungal community of
      the soil was less important at the intensively managed site. Certain durum wheat
      genotypes, such as Strongfield, Plenty, and CDC Verona, were associated with high
      abundance of Paraglomus, and Dominikia was undetected in the rhizosphere of the
      recent cultivars Enterprise, Eurostar, Commander, and Brigade. Genetic variation
      in the association of durum wheat with AM fungi suggests the possibility of
      increasing the sustainability of cropping systems through the use of durum wheat
      genotypes that select highly effective AM fungal taxa residing in the
      agricultural soils of the Canadian prairies.

PMID- 29633626
TI  - The effects of adenine nucleotide perfusion on interstitial adenosine production
      in rat skeletal muscle.
AB  - The purpose of the present study was to utilize the microdialysis technique in
      rat skeletal muscle to perfuse varying concentrations of AMP, ADP, and ATP into
      the interstitium to examine the effects that these adenine nucleotides have on
      the production of adenosine in the interstitial space. Interstitial adenosine
      production appears to be related to the type (ATP, ADP, or AMP) and concentration
      (2-60 MUmol/L) of the adenine nucleotide perfused. Interstitial adenosine levels
      increased (P < 0.05) from baseline (0.18 +/- 0.02 and 0.22 +/- 0.02 MUmol/L) to
      0.23 +/- 0.02 and 0.41 +/- 0.05 MUmol/L following 5 and 30 MUmol/L AMP perfusion,
      respectively. Similarly, perfusion with 30 MUmol/L ADP and 30, 40, and 60 MUmol/L
      ATP resulted in an increase (P < 0.05) in interstitial adenosine concentration
      from baseline (0.25 +/- 0.02, 0.26 +/- 0.02, 0.19 +/- 0.03, and 0.14 +/- 0.02
      MUmol/L) to 0.30 +/- 0.02, 0.32 +/- 0.02, 0.36 +/- 0.04, and 0.33 +/- 0.04
      MUmol/L, respectively. Interestingly, the most prominent increase in interstitial
      adenosine production occurred during the perfusion of 60 MUmol/L ATP (126%
      increase from baseline). These data strongly suggest that interstitial ATP may
      play a more potent role in stimulating interstitial adenosine production as
      compared with ADP or AMP. In addition, interstitial adenosine production can
      occur independent of muscle contraction (voluntary or involuntary) or hypoxia
      when adequate concentrations of adenine nucleotides are available.

PMID- 29633627
TI  - Cardiotoxicity of beta-mimetic catecholamines during ontogenetic development -
      possible risks of antenatal therapy.
AB  - Catecholamines are involved in the regulation of a wide variety of vital
      functions. The beta-adrenergic receptor (beta-AR) - adenylyl cyclase system has
      been identified early in embryogenesis before the heart has received adrenergic
      innervation. The structure of beta-receptors in the immature myocardium is
      similar to that in adults; there are, however, significant quantitative
      developmental changes in the inotropic and chronotropic responsiveness.
      Information on the toxic effect of the beta-AR agonists in the immature heart is
      surprisingly scarce, even though these agents are used in clinical practice both
      during pregnancy and in early postnatal development. Large doses of beta-AR
      agonists induce malformations of the cardiovascular system; the type of change
      depends upon the time at which the beta-AR agonist was administered during
      embryogenesis. During postnatal ontogeny, the cardiotoxicity of beta-AR agonists
      increased from birth to adulthood. It seems likely that despite interspecies
      differences, developmental changes in the cardiac sensitivity to beta-AR agonists
      may exist in all mammals, depending on the degree of maturation of the system
      involved in beta-adrenergic signaling. All the existing data draw attention to
      the possible harmful consequences of the clinical use of beta-AR agonists during
      early phases of cardiac development. Late effects of the early disturbances of
      the cardiac muscle cannot be excluded.

PMID- 29633629
TI  - Letter to the Editor: re Heo et al. (SMMR, November 9 2017).

PMID- 29633628
TI  - 17beta-Estradiol treatment reversed left ventricular dysfunction in castrated
      male rats: an echocardiographic study.
AB  - No data are available on heart function in chronic testosterone deficiency and on
      the effect of estrogen treatment. Eighteen 4-week-old male Lewis rats were
      randomly divided into 3 groups (n = 6): 1 group of sham-operated rats and 2
      groups of castrated rats. Sixty-six weeks after surgery, 1 castrated group
      received a dose of 17beta-estradiol (10 MUg/kg per day) and the remaining 2
      groups received a placebo subcutaneously for 14 days. Left ventricular (LV)
      systolic and diastolic functions were measured by transthoracic echocardiography.
      Castration decreased LV ejection fraction (9%) and fractional shortening (15%)
      and deteriorated LV diastolic function (94%). 17beta-Estradiol treatment
      increased LV ejection fraction (15%) and fractional shortening (31%) and improved
      LV diastolic function (48%). Plasma testosterone concentrations were decreased in
      both castrated groups. In conclusion, chronic testosterone deficiency induced LV
      systolic and diastolic dysfunction; these disorders were reversed by short-term
      treatment with 17beta-estradiol.

PMID- 29633630
TI  - Reply to Walter et al.'s letter to the editor.

PMID- 29633631
TI  - Potentiation of the humoral immune response elicited by a commercial vaccine
      against bovine respiratory disease by Enterococcus faecalis CECT7121.
AB  - Vaccination against pathogens involved in bovine respiratory disease (BRD) is a
      useful tool to reduce the risk of this disease however, it has been observed that
      the commercially available vaccines only partially prevent the infections caused
      by Pasteurella multocida and Mannheimia haemolytica. Therefore, it is recommended
      to search for new adjuvant strategies to minimise the economic impact of this
      respiratory syndrome. A possibility to improve the conventional vaccine response
      is to modulate the immune system with probiotics, since there is accumulating
      evidence that certain immunomodulatory strains administered around the time of
      vaccination can potentiate the immune response. Considering veterinary vaccines
      are frequently tested in murine models, we have developed an immunisation
      schedule in BALB/c mice that allows us to study the immune response elicited by
      BRD vaccine. In order to evaluate a potential strategy to enhance vaccine
      efficacy, the adjuvant effect of Enterococcus faecalis CECT7121 on the murine
      specific humoral immune response elicited by a commercial vaccine against BRD was
      studied. Results indicate that the intragastric administration of E. faecalis
      CECT7121 was able to induce an increase in the specific antibody titres against
      the bacterial components of the BRD vaccines (P. multocida and M. haemolytica).
      The quality of the humoral immune response, in terms of antibody avidity, was
      also improved. Regarding the cellular immune response, although the BRD
      vaccination induced a low specific secretion of cytokines in the spleen cell
      culture supernatants, E. faecalis CECT7121-treated mice showed higher interferon
      gamma production than immunised control mice. Our results allowed us to conclude
      that the administration of E. faecalis CECT7121 could be employed as an adjuvant
      strategy to potentiate humoral immune responses.

PMID- 29633632
TI  - Oral administration of Simbioflora(r) (synbiotic) attenuates intestinal damage in
      a mouse model of 5-fluorouracil-induced mucositis.
AB  - The use of probiotics to prevent or treat mucosal inflammation has been studied;
      however, the combined effect of probiotics and prebiotics is unclear. The aim of
      this study was to test whether oral administration of a synbiotic
      (Simbioflora(r)) preparation containing Lactobacillus paracasei, Lactobacillus
      rhamnosus, Lactobacillus acidophilus and Bifidobacterium lactis plus
      fructooligosaccharide could help control mucosal inflammation in experimental
      mucositis induced by 5-fluorouracil (5-FU). Male BALB/c mice were randomly
      divided into six groups: control (CTL), control + prebiotic (CTL+P), control +
      synbiotic (CTL+S), mucositis (MUC), mucositis + prebiotic (MUC+P), and mucositis
      + synbiotic (MUC+S). Mice from the CTL+S, MUC+S, CTL+P, and MUC+P groups received
      synbiotic or prebiotic daily by oral gavage for 13 days. Mice in the CTL and MUC
      groups received the same volume of saline. On day 11, mice in the MUC, MUC+P, and
      MUC+S groups received an intraperitoneal injection of 300 mg/kg 5-FU to induce
      mucositis. After 72 h, all mice were euthanised. Intestinal permeability,
      intestinal histology, and biochemical parameters were analysed. Group MUC showed
      a greater weight loss and increased intestinal permeability (0.020 counts per min
      [cpm]/g) compared to the CTL group (0.01 cpm/g) P<0.05. Both treatments
      attenuated weight loss compared to the MUC group. Nonetheless, the synbiotic
      caused a greater reduction in intestinal permeability (0.012 cpm/g) compared to
      the MUC (0.020 cpm/g) and MUC+P (0.016 cpm/g) groups P<0.05. Mice in groups MUC+P
      and MUC+S displayed significant recovery of lesions and maintenance of the mucus
      layer. There were no differences in the short-chain fatty acid concentrations in
      the faeces between the MUC and CTL groups (P>0.05). Increased acetate and
      propionate concentrations were evidenced in the faeces of the MUC+P and MUC+S
      groups. Only the synbiotic treatment increased the butyrate concentration
      (P<0.05). The results indicate that administration of synbiotic can decrease
      mucosal damage caused by mucositis.

PMID- 29633633
TI  - Lactobacillus fermentum UCO-979C strongly inhibited Helicobacter pylori SS1 in
      Meriones unguiculatus.
AB  - Searching for bacterial probiotics active upon Helicobacter pylori continue to be
      an important clinical challenge because of the increased prevalence of this
      highly priority pathogen in humans. In this work, we assess the in vivo anti-H.
      pylori SS1 (cagA+/vacAs2m2+) properties of a previously isolated human gastric
      probiotic strain Lactobacillus fermentum UCO-979C by using a Meriones
      unguiculatus (Mongolian gerbil) model. Animals were administered with a saline
      suspension of L. fermentum UCO-979C or H. pylori SS1 as negative and positive
      control for H. pylori colonisation controls, prior to assayed the challenge group
      that was administered with these two species per animal for detecting protective
      activity of the probiotic strain against colonisation. The results showed that L.
      fermentum UCO-979C strongly inhibited the colonisation of H. pylori decreasing up
      to 87% of the colonisation in the antrum by the pathogen, suggesting that this
      probiotic strain has a strong probiotic activity against H. pylori in the most
      valuable animal model for in vivo assays nowadays.

PMID- 29633634
TI  - Manipulation of intestinal dysbiosis by a bacterial mixture ameliorates
      loperamide-induced constipation in rats.
AB  - Constipation has a significant influence on quality of life. Patients with
      constipation have slow waves in their gastrointestinal smooth muscles and less
      faecal water contents, which are closely associated with down-regulation of the
      interstitial cells of Cajal (ICC) in the gastrointestinal muscles and the
      aquaporin protein AQP3 expressed in colon epithelial cells. Recent studies
      supported that patients with constipation have altered intestinal microbial
      structures compared with healthy controls. Intestinal dysbiosis might be one
      possible pathophysiological mechanism causing constipation. Bacterial strains,
      such as Lactobacillus spp., have shown many beneficial effects on the
      amelioration of constipation. However, few studies reported the structural
      changes of intestinal microbiota post-intervention of probiotics. In this study,
      a bacterial mixture was administrated to rats with loperamide-induced
      constipation. Effects of the bacterial mixture on small intestine transit (SIT),
      faecal water content, and the intestinal microbiome in rats were evaluated.
      Meanwhile, we investigated several factors involved in signalling pathways that
      regulate function of ICC and expression of AQP3 to discuss the possible
      underlying molecular mechanisms. Intervention of the bacterial mixture improved
      SIT and faecal water content in constipated rats. The up-regulation of C-kit/SP
      signalling pathways in ICC and AQP3 significantly contributed to improvements.
      These changes were closely associated with the manipulation of intestinal
      dysbiosis in constipated rats. Furthermore, our results revealed the important
      role of intestinal microbiota in affecting gut motility through regulation of
      serotonin biosynthesis. This monoamine neurotransmitter, secreted from
      enterochromaffin cells, up-regulated both substance P/neurokinin 1 receptors
      pathway of ICC and the expression of AQP3 in intestinal epithelial cells. Our
      study suggested that the disrupted microbiome in patients could be a potential
      therapeutic target for the improvement of constipation.

PMID- 29633635
TI  - Prophylactic Bifidobacterium adolescentis ATTCC 15703 supplementation reduces
      partially allergic airway disease in Balb/c but not in C57BL/6 mice.
AB  - Allergic asthma is a chronic disease mainly characterised by eosinophil
      inflammation and airway remodelling. Many studies have shown that the gut
      microbiota of allergic individuals differs from that of non-allergic individuals.
      Although high levels of bifidobacteria have been associated with healthy persons,
      Bifidobacterium adolescentis ATCC 15703, a gut bacteria, has been associated with
      allergic individuals in some clinical studies. The relationship between B.
      adolescentis ATCC 15703 and asthma or allergies has not been well elucidated, and
      its effect may be dependent on the host's genetic profile or disease state. To
      elucidate this question, we evaluated the role of preventive B. adolescentis ATCC
      15703 treatment on experimental allergic airway inflammation in two genetically
      different mouse strains, Balb/c and C57BL/6 (B6). Balb/c mice display a greater
      predisposition to develop allergic responses than B6 mice. Oral preventive
      treatment with B. adolescentis ATCC 15703 modulated experimental allergic airway
      inflammation, specifically in Balb/c mice, which showed decreased levels of
      eosinophils in the airway. B6 mice did not exhibit any significant alterations in
      eosinophils but showed an increased influx of total leukocytes and neutrophils
      into the airway. The mechanism underlying the beneficial effects of these
      bacteria in experimental allergic mice may involve products of bacteria
      metabolism, as dead bacteria did not mimic the ability of live B. adolescentis
      ATCC 15703 to attenuate the influx of eosinophils into the airway. To conclude,
      preventive oral B. adolescentis ATCC 15703 treatment can attenuate the major
      characteristic of allergic asthma, eosinophil airway influx, in Balb/c but not B6
      mice. These results suggest that oral treatment with this specific live bacterial
      strain may have therapeutic potential for the treatment of allergic airway
      disease, although its effect is mouse-strain-dependent.

PMID- 29633636
TI  - Krill oil, vitamin D and Lactobacillus reuteri cooperate to reduce gut
      inflammation.
AB  - Current research into original therapies to treat intestinal inflammation is
      focusing on no-drug therapies. KLD is a mixture of krill oil (KO), probiotic
      Lactobacillus reuteri (LR), and vitamin D (VitD3). The aim of this study was to
      assess in vitro and in vivo the potential cooperative effects of KLD in reducing
      gut inflammation. Colorectal adenocarcinoma cell lines, CACO2 and HT29, and
      C57BL/6 mice were used for in vitro and in vivo analyses, respectively. Cells
      were exposed to cytomix (interferon gamma + tumour necrosis factor alpha (TNF
      alpha)) to induce inflammation or co-exposed to cytomix and KO, LR and VitD3
      alone or to cytomix and KLD. Animals were treated for 7 days with dextran sodium
      sulphate (DSS) to induce colitis or with DSS and KLD. In vitro assays: F-actin
      expression was analysed by immunofluorescence; scratch test and trans-epithelial
      electric resistance test were performed to measure wound healing;
      adhesion/invasion assays of adhesive and invasive Escherichia coli (AIEC)
      bacteria were made; mRNA expression of TNF-alpha, interleukin (IL)-8 and vitamin
      D receptor (VDR) was detected by quantitative PCR. In vivo assays: body weight,
      clinical score, histological score and large intestine weight and length were
      estimated; mRNA expression of TNF-alpha, IL-1beta, IL-6, IL-10 by quantitative
      PCR; VDR expression was detected by quantitative PCR and immunohistochemistry. In
      vitro: KLD restores epithelial cell-cell adhesion and mucosal healing during
      inflammation, while decreases the adhesiveness and invasiveness of AIEC bacteria
      and TNF-alpha and IL-8 mRNA expression and increases VDR expression. In vivo: KLD
      significantly improves body weight, clinical score, histological score and large
      intestine length of mice with DSS-induced colitis and reduces TNF-alpha, IL-1beta
      and IL-6 mRNA levels, while increases IL-10 mRNA and VDR levels. KLD has
      significant effects on the intestinal mucosa, strongly decreasing inflammation,
      increasing epithelial restitution and reducing pathogenicity of harmful commensal
      bacteria.

PMID- 29633637
TI  - Multifactorial inhibition of lactobacilli against the respiratory tract pathogen
      Moraxella catarrhalis.
AB  - Probiotics, mainly lactic acid bacteria (LAB), are widely focused on
      gastrointestinal applications. However, recent microbiome studies indicate that
      LAB can be endogenous members of other human body sites such as the upper
      respiratory tract (URT). Interestingly, DNA-based microbiome research suggests an
      inverse correlation between the presence of LAB and the occurrence of potential
      pathogens, such as Moraxella catarrhalis, an important URT pathogen linked to
      otitis media, sinusitis and chronic obstructive pulmonary disease. However, a
      direct interaction between these microbes has not been explored in detail. This
      study investigated the direct antipathogenic effects of Lactobacillus species,
      including several well-documented probiotic strains, on M. catarrhalis using agar
      based assays, time course analysis, biofilm assays and minimal inhibitory
      concentration (MIC) testing. These assays were performed using spent culture
      supernatans (SCS) at two pHs (4.3 and 7) and D- and/or L-lactic acid at three pHs
      (2, 4 and 7). In addition, cell line assays for adhesion competition and
      immunomodulation were used to substantiate the inhibitory effect of lactobacilli
      against M. catarrhalis. A proportion of Lactobacillus strains, including the
      model probiotic Lactobacillus rhamnosus GG, showed a strong and direct activity
      against M. catarrhalis. Screening of the activity of the SCS after different
      treatments demonstrated that lactic acid has an important antimicrobial activity
      against this pathogen - at least in vitro - with mean MIC values for D- and L
      lactic acid varying between 0.5 and 27 g/l depending on the pH. Furthermore, L.
      rhamnosus GG also decreased the adhesion of M. catarrhalis to human airway
      epithelial Calu-3 cells with more than 50%, and the expression of mucin MUC5AC,
      pro-inflammatory cytokines interleukin (IL)-8, IL-1beta, and tumor necrosis
      factor-alpha at least 1.2 fold. This study suggests that several lactobacilli and
      their key metabolite lactic acid are possible candidates for probiotic
      therapeutic interventions against URT infections.

PMID- 29633638
TI  - Lipoteichoic acids are embedded in cell walls during logarithmic phase, but
      exposed on membrane vesicles in Lactobacillus gasseri JCM 1131T.
AB  - Lipoteichoic acid (LTA) is a cell surface molecule specific to Gram-positive
      bacteria. How LTA localises on the cell surface is a fundamental issue in view of
      recognition and immunomodulation in hosts. In the present study, we examined LTA
      localisation using strain JCM 1131T of Lactobacillus gasseri, which is a human
      intestinal lactic acid bacterium, during various growth phases by immunoelectron
      microscopy. We first evaluated the specificity of anti-LTA monoclonal antibody
      clone 55 used as a probe. The glycerophosphate backbone comprising almost intact
      size (20 to 30 repeating units) of LTA was required for binding. The antibody did
      not bind to other cellular components, including wall-teichoic acid.
      Immunoelectron microscopy indicated that LTA was embedded in the cell wall during
      the logarithmic phase, and was therefore not exposed on the cell surface. Similar
      results were observed for Lactobacillus fermentum ATCC 9338 and Lactobacillus
      rhamnosus ATCC 7469T. By contrast, membrane vesicles were observed in the
      logarithmic phase of L. gasseri with LTA exposed on their surface. In the
      stationary and death phases, LTA was exposed on cell wall-free cell membrane
      generated by autolysis. The dramatic alternation of localisation in different
      growth phases and exposure on the surface of membrane vesicles should relate with
      complicated interaction between bacteria and host.

PMID- 29633639
TI  - Stool and urine trefoil factor 3 levels: associations with symptoms, intestinal
      permeability, and microbial diversity in irritable bowel syndrome.
AB  - Previously we showed that urine trefoil factor 3 (TFF3) levels were higher in
      females with irritable bowel syndrome (IBS) compared to non-IBS females. To
      assess if TFF3 is associated with symptoms and/or reflect alterations in
      gastrointestinal permeability and gut microbiota in an IBS population, we
      correlated stool and urine TFF3 levels with IBS symptoms, intestinal
      permeability, stool microbial diversity and relative abundance of predominant
      bacterial families and genera. We also tested the relationship of stool TFF3 to
      urine TFF3, and compared results based on hormone contraception use. Samples were
      obtained from 93 females meeting Rome III IBS criteria and completing 4-week
      symptom diaries. TFF3 levels were measured by ELISA. Permeability was assessed
      with the urine lactulose/mannitol (L/M) ratio. Stool microbiota was assessed
      using 16S rRNA. Stool TFF3, but not urine TFF3, was associated positively with
      diarrhoea and loose stool consistency. Higher stool TFF3 was also associated with
      lower L/M ratio and microbial diversity. Of the 20 most abundant bacterial
      families Mogibacteriaceae and Christensenellaceae were inversely related to stool
      TFF3, with only Christensenellaceae remaining significant after multiple
      comparison adjustment. There were no significant relationships between stool or
      urine TFF3 levels and other symptoms, nor between stool and urine levels. In
      premenopausal females, urine TFF3 levels were higher in those reporting hormone
      contraception. Collectively these results suggest that higher stool TFF3 levels
      are associated with IBS symptoms (loose/diarrhoeal stools), lower gut
      permeability, and altered stool bacteria composition (decreased diversity and
      decreased Christensenellaceae), which further suggests that TFF3 may be an
      important marker of host-bacteria interaction.

PMID- 29633640
TI  - Probiotic properties of native Lactobacillus spp. strains for dairy calves.
AB  - The use of native microorganisms with probiotic capacity is an alternative tool
      for the treatment and prevention of several diseases that affect animals, such as
      neonatal calf diarrhoea. The selection of probiotic strains within a collection
      is based on different in vitro and in vivo assays, which predict their potential.
      The aim of this study was to characterise a group of native Lactobacillus spp.
      strains isolated from faeces of healthy calves using an in vitro approach and to
      assess their ability to colonise the gastrointestinal tract (GIT) of calves.
      Native Lactobacillus spp. strains were evaluated on their capacity to survive low
      pH conditions and bile salts presence, biofilm formation and adhesion to both
      mucus and Caco-2 cells. Based on the in vitro characterisation, four strains
      (Lactobacillus johnsonii TP1.1, Lactobacillus reuteri TP1.3B, L. johnsonii TP1.6
      and Lactobacillus amylovorus TP8.7) were selected to evaluate their capacity to
      colonise and persist in the GIT of calves. The assessment of enteric persistence
      involved an in vivo assay with oral administration of probiotics and
      quantification in faeces of the administered bacterial species with real-time
      quantitative PCR (qPCR). The study was conducted using 15 calves (1-month-old)
      which were divided into five groups of three animals, four of which were treated
      with four different selected strains and one was the control group. Strains
      TP1.3B and TP1.6 managed to persist in treated animals until ten days after the
      end of the administration period, indicating that they could be promising
      candidates for the design of probiotics for calves.

PMID- 29633641
TI  - Lactobacillus johnsonii N6.2 diminishes caspase-1 maturation in the
      gastrointestinal system of diabetes prone rats.
AB  - The cells of the gastrointestinal (GI) epithelium are the first to contact the
      microbiota and food components. As a direct consequence of this, these cells are
      the first line of defence and key players in priming the immune response. One of
      the first responses against GI insults is the formation of the inflammasome, a
      multiprotein complex assembled in response to environmental threats. The
      formation of the inflammasome regulates caspase-1 by cleaving it into its active
      form. Once activated, caspase-1 can cleave interleukin-1beta (IL-1beta), which
      promotes adaptive and humoral immunity. Some strains, like Lactobacillus
      johnsonii N6.2, are able to modulate the biosynthesis of important host
      metabolites mediating inflammation. Of these metabolites are the pro-inflammatory
      kynurenines. L. johnsonii N6.2 is able to downregulate kynurenines biosynthesis
      via a redox active mechanism negatively affecting indoleamine 2,3-dioxygenase
      activity. In this study, we evaluated the effects of L. johnsonii N6.2 combined
      with the natural antioxidant and anti-inflammatory molecule rosmarinic acid (RA).
      Inflammasome assembly and the kynurenine pathway were evaluated in GI samples of
      BioBreeding diabetes-prone (BB-DP) rats. In this work, BB-DP rats were fed daily
      with RA, L. johnsonii N6.2; or both combined. The transcriptional rate and
      proteins levels of inflammasome and kynurenine pathway components in ileum tissue
      were evaluated. Elevated levels of pro-caspase-1 were observed in rats fed with
      L. johnsonii, while RA had no effect on pro-caspase-1 expression. Western blot
      assays demonstrated that L. johnsonii fed rats showed lower levels of mature
      caspase-1, when compared to the other treatments. Furthermore, IL-1beta
      maturation followed a similar pattern across the treatments. Differences were
      also observed between treatments in expression levels of key enzymes in the
      kynurenine pathway. These findings support the role of L. johnsonii in modulating
      the assembly of the inflammasome as well as some steps of the pro-inflammatory
      kynurenine pathway.

PMID- 29633642
TI  - A synbiotic mixture of scGOS/lcFOS and Bifidobacterium breve M-16V increases
      faecal Bifidobacterium in healthy young children.
AB  - Little is known about the impact of nutrition on toddler gut microbiota. The
      plasticity of the toddler gut microbiota indicates that nutritional modulation
      beyond infancy could potentially impact its maturation. The objective of this
      study was to determine the effect of consuming Young Child Formula (YCF)
      supplemented with short chain galactooligosaccharides and long chain
      fructooligosaccharides (scGOS/lcFOS, ratio 9:1) and Bifidobacterium breve M-16V
      on the development of the faecal microbiota in healthy toddlers. A cohort of 129
      Thai children aged 1-3 years were included in a randomised controlled clinical
      study. The children were assigned to receive either YCF with 0.95 g/100 ml of
      scGOS/lcFOS and 1.8*107 cfu/g of B. breve M-16V (Active-YCF) or Control-YCF for
      12 weeks. The composition and metabolic activity of the faecal microbiota, and
      the level of secretory immunoglobulin A were determined in the stool samples. The
      consumption of Active-YCF increased the proportion of Bifidobacterium (mean 27.3%
      at baseline to 33.3%, at week 12, P=0.012) with a difference in change from
      baseline at week 12 between the Active and Control of 7.48% (P=0.030). The
      consumption of Active-YCF was accompanied with a more acidic intestinal milieu
      compared to the Control-YCF. The pH value decreased statistically significantly
      in the Active-YCF group from a median of 7.05 at baseline to 6.79 at week 12
      (P<0.001). The consumption of Active-YCF was associated with a softer pudding
      like stool consistency compared to the Control-YCF. At week 6 and week 12, the
      between-group difference in stool consistency was statistically significant
      (P=0.004 and P<0.001, respectively). A Young Child Formula supplemented with
      scGOS/lcFOS and B. breve M-16V positively influences the development of the
      faecal microbiota in healthy toddlers by supporting higher levels of
      Bifidobacterium. The synbiotic supplementation is also accompanied with a more
      acidic intestinal milieu and softer stools.

PMID- 29633643
TI  - Degradation of food-derived opioid peptides by bifidobacteria.
AB  - Some food-derived opioid peptides have been reported to cause diseases, such as
      gastrointestinal inflammation, celiac disease, and mental disorders.
      Bifidobacterium is a major member of the dominant human gut microbiota,
      particularly in the gut of infants. In this study, we evaluated the potential of
      Bifidobacterium in the degradation of food-derived opioid peptides. All strains
      tested showed some level of dipeptidyl peptidase activity, which is thought to be
      involved in the degradation of food-derived opioid peptides. However, this
      activity was higher in bifidobacterial strains that are commonly found in the
      intestines of human infants, such as Bifidobacterium longum subsp. longum, B.
      longum subsp. infantis, Bifidobacterium breve and Bifidobacterium bifidum, than
      in those of other species, such as Bifidobacterium animalis and Bifidobacterium
      pseudolongum. In addition, some B. longum subsp. infantis and B. bifidum strains
      showed degradative activity in food-derived opioid peptides such as human and
      bovine milk-derived casomorphin-7 and wheat gluten-derived gliadorphin-7. A
      further screening of B. bifidum strains revealed some bifidobacterial strains
      that could degrade all three peptides. Our results revealed the potential of
      Bifidobacterium species in the degradation of food-derived opioid peptides,
      particularly for species commonly found in the intestine of infants. Selected
      strains of B. longum subsp. infantis and B. bifidum with high degradative
      capabilities can be used as probiotic microorganisms to eliminate food-derived
      opioid peptides and contribute to host health.

PMID- 29633644
TI  - Effects of heat-treated Lactobacillus crispatus KT-11 strain consumption on
      improvement of oral cavity environment: a randomised double-blind clinical trial.
AB  - Heat-treated lactic acid bacteria is added to some foods because it is easier to
      store and transport, and have less interference with other food ingredient
      compared with living lactic acid bacteria. We have reported that oral
      administration of heat-treated Lactobacillus crispatus KT-11 strain (KT-11)
      suppressed the symptoms of periodontal disease in mice orally infected with
      Porphyromonas gingivalis. However, the preventive effect of KT-11 on periodontal
      disease in human is unclear. The aim of this randomised double-blind clinical
      trial was to examine the effects of KT-11 consumption on the oral environment in
      healthy volunteers. Sixteen healthy volunteers were randomly assigned to two
      groups (KT-11 or placebo), and they consumed a KT-11 food tablet (1.2*1010 KT-11
      cells) or a placebo food tablet (without KT-11) every day for 4 weeks. Clinical
      parameters including numbers of major periodontopathic bacteria in saliva, plaque
      score, gum conditions, and oral mucosal fluid level were evaluated at weeks 0 and
      4. Amount of change in P. gingivalis numbers decreased in the KT-11 group
      compared to that in the placebo group at week 4. Female participants in the KT-11
      group had decreased plaque scores, reddish tinge, and gingival swelling scores
      compared to those in the placebo group at week 4. Furthermore, male participants
      in the KT-11 group demonstrated increased oral mucosa fluid scores. These
      clinical findings suggest that daily KT-11 intake can prevent periodontal disease
      through the improvement of oral conditions.

PMID- 29633645
TI  - Enterococcus faecium SF68 as a model for efficacy and safety evaluation of
      pharmaceutical probiotics.
AB  - As normal inhabitants of diverse ecosystems, including the human gastrointestinal
      tract, the enterococci, and especially the two species Enterococcus faecalis and
      Enterococcus faecium, can be considered ubiquitous with regard to our natural
      environment. E. faecium has gained special importance thanks to beneficial
      strains marketed as probiotics, and because of its beneficial role in traditional
      fermented foods such as artisanal cheeses in some Southern European countries.
      Yet, following reports on the increasing association of some enterococcal strains
      with nosocomial infections such as endocarditis and bacteraemia, it became
      evident that strains from clinical origin are frequently highly resistant to
      'last-defence-line' antibiotics such as the glycopeptide derivatives. For this
      reason enterococci have been classified in risk group 2 in the European Directive
      93/88. With this paper it is intended to clarify the uncertain situation around
      the safety of the species E. faecium, also with referring to intra-species
      heterogeneity. In fact, well established scientific and surveillance data support
      the safety of some probiotic E. faecium strains for both human and animal
      applications. As a model, summarising yet extensive information is provided on
      the efficacy and safety of E. faecium SF68(r), a pharmaceutical probiotic with a
      long history of safe use. We propose the approach presented in this review as a
      model for the evaluation of safety of probiotic strains of this species.

PMID- 29633646
TI  - Effect of Lactobacillus rhamnosus and Bifidobacterium lactis on gingival health,
      dental plaque, and periodontopathogens in adolescents: a randomised placebo
      controlled clinical trial.
AB  - To determine the effect of a probiotic combination of Lactobacillus rhamnosus GG
      (LGG) and Bifidobacterium lactis BB-12 on the gingival health, dental plaque
      accumulation, and the oral carriage of four putative periodontal pathogens in
      healthy adolescents. 108 schoolboys, aged 13-15 years, participated in this
      study. They were divided into two groups: probiotics (n=54) and placebo (n=54).
      Both groups received two probiotic-laced or placebo lozenges twice a day during a
      four-week period. Plaque Index (PI) and Gingival Index (GI) were recorded at
      baseline and after four weeks. Salivary and plaque carriage of Aggregatibacter
      actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia,
      Fusobacterium nucleatum were also monitored likewise. 101 subjects completed the
      study. A statistically significant reduction in GI was seen in the probiotic
      group as compared to the placebo group (P=0.012). A reduction in PI was found for
      both groups, with no difference observed between the groups after intervention
      (P=0.819). Probiotic lozenges significantly reduced levels of A.
      actinomycetemcomitans and F. nucleatum in saliva and plaque (P<0.05) and levels
      of P. gingivalis in plaque (P<0.05), while no significant changes were found in
      the control group. A significant reduction (P<0.001) was also noted in the total
      salivary bacterial counts of the test group. The short-term daily consumption of
      LGG and BB-12 probiotic lozenges improved the gingival health in adolescents and
      decreased the microbial counts of A. actinomycetemcomitans, and P. gingivalis.
      Hence probiotic supplements may serve as a simple adjunct to standard oral care
      for promoting the oral health in adolescents.

PMID- 29633647
TI  - Lactobacillus fermentum L930BB and Bifidobacterium animalis subsp. animalis IM386
      initiate signalling pathways involved in intestinal epithelial barrier
      protection.
AB  - The manipulation of intestinal microbiota with beneficial microbes represents a
      promising alternative or adjunct therapy in gastrointestinal disorders and
      inflammation. The current study aims to clarify the signalling pathways and
      evaluate the possible beneficial effects of the combination of two strains. We
      used a dextran sulphate sodium (DSS)-induced mouse model of colitis. RNA
      extracted from the middle part of the colon tissue was used for examination of
      the global gene expression with Affymetrix microarrays. An enrichment analysis of
      the KEGG pathways was performed, and a subset of genes associated with intestinal
      epithelial barrier function was verified with qPCR. A clinical condition
      assessment of the differently treated mice revealed that the combination of these
      two bacterial strains was safe for use as a dietary supplement. All animals
      treated with DSS had affected colons and suffered weight loss. There were very
      small differences between the diseased groups, although the depth of inflammation
      was lower when cyclosporine A or the strain mixture was used. We discovered that
      the prophylactic administration of the Lactobacillus fermentum L930BB (L930BB)
      and Bifidobacterium animalis subsp. animalis IM386 (IM386) strains led to an anti
      apoptotic pathway through phosphatidylinositol-4,5-bisphosphate 3-kinase
      (PI3K)/Akt and to the activation of pathways involved in the regulation of actin
      cytoskeleton via protein kinase C and GTPases. Reorganisation of actin
      cytoskeleton and decreased apoptosis are both helpful in intestinal epithelial
      cell reconstitution. We confirm important previous observations, showing that
      these pathways are downstream targets of Toll-like receptor 2 and fibroblast
      growth factor initiated signalling. Taken together, these results suggest that
      the combination of L930BB and IM386 could aid in the regeneration of the
      intestinal epithelium during pathogenesis via pattern recognition receptors and
      the stimulation of growth factor synthesis.

PMID- 29633648
TI  - Self reported involvement in emergency medicine among GPs in Norway.
AB  - OBJECTIVE: To examine general practitioners' (GPs') perception of their role in
      emergency medicine and participation in emergency services including ambulance
      call outs, and the characteristics of the GPs and casualty clinics associated
      with the GPs' involvement in emergency medicine. DESIGN: Cross-sectional online
      survey. SETTING: General practice. SUBJECTS: General practitioners in Norway (n =
      1002). MAIN OUTCOME MEASURES: Proportion of GPs perceiving that they have a large
      role in emergency medicine, regularly being on call, and the proportion of
      ambulance callouts with GP participation. RESULTS: Forty six percent of the GPs
      indicated that they play a large role in emergency medicine, 63 percent of the
      GPs were regularly on call, and 28 percent responded that they usually took part
      in ambulance call outs. Multivariable logistic regression analyses indicated that
      these outcomes were strongly associated with participation in multidisciplinary
      training. Furthermore, the main outcomes were associated with traits commonly
      seen at smaller casualty clinics such as those with an absence of nursing
      personnel and extra physicians, and based on the distance to the hospital.
      CONCLUSION: Our findings suggest that GPs play an important role in emergency
      medicine. Multidisciplinary team training may be important for their continued
      involvement in prehospital emergencies. Key Points   Health authorities and other
      stakeholders have raised concerns about general practitioner's (GPs)
      participation in emergency medicine, but few have studied opinions and
      perceptions among the GPs themselves.   * Norwegian GPs report playing a large
      role in emergency medicine, regularly being on call, and taking part in selected
      ambulance call outs.   * A higher proportion of GPs who took part in team
      training perceived themselves as playing a large role in emergency medicine,
      regularly being on call, and taking part in ambulance call outs.   * These
      outcomes were also associated with attributes commonly seen at smaller casualty
      clinics.

PMID- 29633649
TI  - Functional energetic responses and individual variance of the human brain
      revealed by quantitative imaging of adenosine triphosphate production rates.
AB  - Cellular ATP energy metabolism and regulation are essential for brain function
      and health. Given the high ATP expenditure at resting-state, it is not yet clear
      how the human brain at working-state can effectively regulate ATP production to
      meet higher energy requirement. Through quantitative measurement of regional
      cerebral ATP production rates and associated neurophysiological parameters in
      human visual cortex at rest and during visual stimulation, we found significant
      stimulus-induced and highly correlated neuroenergetic changes, indicating
      distinctive and complementary roles of the ATP synthesis reactions in supporting
      evoked neuronal activity and maintaining ATP homeostasis. We also uncovered large
      individual variances in the neuroenergetic responses and significant reductions
      in intracellular [H+] and free [Mg2+] during the stimulation. These results
      provide new insights into the mechanism underlying the brain ATP energy
      regulation and present a sensitive and much-needed neuroimaging tool for
      quantitatively assessing neuroenergetic state in healthy and diseased human
      brain.

PMID- 29633650
TI  - Minimization of the perianal infection rate of hematological malignancies with
      agranulocytosis by quality control circle activity and patient-hospital-student
      win-win concept.
AB  - Objective The agranulocytosis-associated perianal infection (PI) rate ranges from
      60% to 100% among patients with hematopoietic malignancies. In this study, we
      assessed the efficacy of a quality control circle (QCC) to minimize the PI rate.
      Methods Among 274 patients with severe immunodeficiency (agranulocytosis of >=2
      weeks) in our bone marrow transplantation center, the PI rate was 17.20%. A QCC
      was established following the 10 steps of the plan-do-check-act (PDCA) model;
      this was scientifically supported by culturing the bacterial colony from
      patients' perianal skin to determine the sanitization effect and interval time.
      Because a warm aqueous solution of potassium permanganate is recommended for
      sanitization, the bacterial colony culture was also used to determine the proper
      drug concentration, water temperature, and soaking time. All procedures were
      standardized. Patients, hospital staff, and medical students were enrolled into
      the QCC team based on the patient-hospital-student (PHS) win-win concept. Results
      After establishment of the PDCA model, the PI rate among 253 patients decreased
      from 17.20% to 5.93% and remained at 5.25% during the following year. The medical
      expenses and length of hospital stay consequently decreased. Conclusion The QCC
      and PHS win-win concept can reduce the PI rate and promote medical quality.

PMID- 29633651
TI  - Age/disease duration influence on activities of daily living and quality of life
      after levodopa-carbidopa intestinal gel in Parkinson's disease.
AB  - AIM: To determine if age and Parkinson's disease duration at therapy initiation
      influence the efficacy of levodopa-carbidopa intestinal gel (LCIG) on quality of
      life and activities of daily living. PATIENTS & METHODS: This post hoc analysis
      assessed subgroups of patients stratified by baseline age, disease duration,
      hours/day of 'off' time and levodopa equivalent dose. Patients' data were
      collected from the GLORIA study, a 24-month observational registry evaluating
      long-term effectiveness of LCIG. RESULTS & CONCLUSION: LCIG therapy led to
      sustained improvements in quality of life irrespective of patient age and disease
      duration at baseline. Improvements in activities of daily living were observed
      across all subgroups, particularly in younger patients, patients with shorter
      disease duration and in patients with the highest baseline levodopa equivalent
      dose.

PMID- 29633652
TI  - Music Therapy Reduces Radiotherapy-Induced Fatigue in Patients With Breast or
      Gynecological Cancer: A Randomized Trial.
AB  - PURPOSE: To investigate the influence of music therapy on the reduction of
      fatigue in women with breast or gynecological malignant neoplasia during
      radiotherapy, since it is one of the most frequent side effects of this type of
      treatment, and may interfere with self-esteem, social activities, and quality of
      life. EXPERIMENTAL DESIGN: Randomized controlled trial (control group [CG] and
      music therapy group [MTG]) to assess fatigue, quality of life, and symptoms of
      depression in women undergoing radiotherapy using the Functional Assessment of
      Cancer Therapy: Fatigue (FACT-F) version 4, Functional Assessment of Cancer
      Therapy-General (FACT-G) version 4, and Beck Depression Inventory in 3 separate
      times, namely, during the first week of radiotherapy, on the week of the
      intermediary phase, and during the last week of radiotherapy. Individual 30- to
      40-minute sessions of music therapy with the presence of a trained music
      therapist were offered to participants. RESULTS: In this study, 164 women were
      randomized and 116 (63 CG and 53 MTG) were included in the analyses, with mean
      age of 52.90 years (CG) and 51.85 years (MTG). Participants in the MTG had an
      average of 10 music therapy sessions, totaling 509 sessions throughout the study.
      FACT-F results were significant regarding Trial Outcome Index ( P = .011), FACT-G
      ( P = .005), and FACT-F ( P = .001) for the MTG compared with the CG.
      CONCLUSIONS: Individual music therapy sessions may be effective to reduce fatigue
      related to cancer and symptoms of depression, as well as to improve quality of
      life for women with breast or gynecological cancer undergoing radiotherapy.
      Further well-designed research studies are needed to adequately determine the
      effects of music therapy on fatigue.

PMID- 29633653
TI  - Is there any relationship between serum levels of total bilirubin and the
      severity of erectile dysfunction?
AB  - OBJECTIVE: Recent studies have shown that atherosclerosis is associated with
      erectile dysfunction and the serum bilirubin level. In this study, the serum
      total bilirubin levels of patients with erectile dysfunction were measured to
      investigate the relationship between the levels of erectile dysfunction and total
      bilirubin. METHODS: A total of 94 patients with erectile dysfunction were divided
      into three groups; severe erectile dysfunction (33 patients), moderate erectile
      dysfunction (31 patients), and mild erectile dysfunction (30 patients). In
      addition, a control group was formed with 31 healthy men. The International Index
      of Erectile Function-5 Questionnaire was used to measure the quality of erection
      in all the groups. The body mass index was calculated for all the participants.
      The serum glucose, low-density lipoprotein and high-density lipoprotein,
      cholesterol, triglyceride, total bilirubin, and total testosterone levels were
      also determined. RESULTS: No statistically significant difference was observed
      between the groups in terms of the mean age, hypertension, smoking status,
      alcohol use, cardiovascular diseases, hepatobiliary disease, diabetes mellitus,
      and levels of total testosterone, low-density lipoprotein-cholesterol, and
      triglyceride. However, high-density lipoprotein, body mass index, and total
      bilirubin were significantly lower compared to the control group (p < 0.001). The
      serum total bilirubin level was found to be 0.41 +/- 0.21 ng/dL in the severe
      erectile dysfunction, 0.43 +/- 0.19 ng/dL in the moderate erectile dysfunction,
      and 0.48 +/- 0.11 ng/dL in the mild erectile dysfunction groups (p < 0.001).
      CONCLUSION: Considering the significant differences between the erectile
      dysfunction and control groups in terms of serum total bilirubin levels, a low
      level of bilirubin may have a role in the etiology of erectile dysfunction.

PMID- 29633654
TI  - Comment to the reply letter: re Walter et al.'s letter to the editor.

PMID- 29633655
TI  - Kick Scooter Injuries in Children and Adolescents: Minor Fractures and Bruise.
AB  - BACKGROUND:: Kick scooters are popular among children in both transportation and
      recreational activities. The aim of this retrospective study was to assess the
      incidence of and injury patterns associated with kick scooter accidents in school
      aged children and adolescents. METHODS:: All 171 patients at the age of 7-15
      years who were treated for kick scooter-related injuries in the metropolitan
      Helsinki area, Southern Finland from January 2008 to December 2013 were included.
      Electronic medical records were reviewed and Pediatric Trauma Scores and Injury
      Severity Scores were utilized to assess the injuries. RESULTS:: The annual number
      of patients increased from 7 in 2008 to 55 in 2013. Almost all patients (94%, n =
      161) were injured after a fall from their own height. Most patients (n = 118;
      69%) were diagnosed with a fracture but only 26 patients (15%) required surgical
      procedures under general anesthesia. Pediatric Trauma Scores were low and only
      one patient had an Injury Severity Score > 15 which can be considered major
      trauma. CONCLUSION:: Most injuries acquired from kick scooter injuries were
      easily treatable fractures and bruises. Considering the background population of
      105,000 in the respective age group and the 6-year period of data collection from
      tertiary care, scooting seems a safe means of increasing the physical activity
      levels of school-aged children and adolescents.

PMID- 29633656
TI  - Could spinal anesthesia be a choice for retrograde intrarenal surgery.
AB  - OBJECTIVE:: In this study, we aimed to compare cases of retrograde intrarenal
      surgery performed under spinal or general anesthesia through investigating
      relevant parameters for the first time in the literature. MATERIAL AND METHOD::
      In total, 86 patients with diagnosis of kidney stone who were treated by
      retrograde intrarenal surgery were included in this randomized controlled
      prospective study. In total, 43 of these operations were performed under spinal
      anesthesia (group I) and 43 were performed under general anesthesia (group II).
      The groups were compared in terms of demographic features, American Society of
      Anesthesiologists score, duration of operation, complication rates, postoperative
      visual analogue scale, postoperative hospitalization period, stone-free rates,
      and cost value ratios. RESULTS:: There were no significant differences between
      the two groups in terms of demographic findings, preoperative stone loads,
      postoperative stone-free rates, complication rates and postoperative
      hospitalization periods (p > 0.05). Postoperative visual analogue scale scores
      and cost value ratios were found statistically significantly lower in the spinal
      anesthesia group (group I) when compared with the general anesthesia group (group
      II; p < 0.001). CONCLUSION:: Performing retrograde intrarenal surgery in the
      presence of spinal anesthesia is equally effective with general anesthesia.
      Spinal anesthesia also appears to be a more advantageous method due to
      statistically significantly lower mean postoperative pain scores and treatment
      cost value ratios.

PMID- 29633657
TI  - The role of blood neutrophil count and the neutrophil-to-lymphocyte ratio as a
      predictive factor for prostate biopsy results.
AB  - BACKGROUND:: It is apparent that prostate cancer has harmful effects on the
      erythrocytes, leucocytes, and platelets. In addition, it has been suggested that
      the toxic granules in neutrophils lead to inflammation in the cancerous tissues
      besides the activation of monocytes, so in this study we aimed to evaluate the
      blood neutrophil count besides the neutrophil-to-lymphocyte ratio as a predictive
      factor for prostate biopsy results and their relationship with prostate cancer
      grade in patients undergoing biopsy of the prostate. METHODS:: For all men with
      irritative lower urinary tract symptoms visiting Hasheminezhad Hospital from
      January to July 2015, in case of having a suspicious digital rectal examination
      or aged above 40 years, prostate-specific antigen was requested and in case of
      abnormal results, they underwent prostate biopsy. In order to examine the study
      hypothesis, the blood neutrophil count and the neutrophil-to-lymphocyte ratio
      were measured and compared with the abnormal prostate-specific antigen results
      and suspicious digital rectal examination. RESULTS:: Among the 500 referred
      samples for biopsy, 352 (70.4%) had a negative biopsy result, while it was
      positive in the other 148 (29.6). The mean neutrophil count showed no statistical
      difference regarding the biopsy results (p = 0.381). When measuring the
      neutrophil-to-lymphocyte ratio again with biopsy results, no statistically
      significant difference was obtained based on the biopsy results (p = 0.112).
      CONCLUSION:: Neutrophil count and neutrophil-to-lymphocyte ratio cannot be
      predictive factors for positive prostate cancer biopsy.

PMID- 29633658
TI  - Development of Electronic Chemotherapy Roadmaps for Pediatric Oncology Patients.
AB  - A chemotherapy roadmap is a summary of the chemotherapy plan for a pediatric
      oncology patient. Chemotherapy roadmaps exist as paper documents for most, if not
      all, pediatric oncology programs. Paper chemotherapy roadmaps are associated with
      risks that can negatively affect the safety of the chemotherapy process. This
      institution explored the feasibility of converting paper chemotherapy roadmaps
      into an electronic form. The pediatric information systems team developed an
      innovative computer application that can generate electronic chemotherapy
      roadmaps, and the pediatric oncology program established a novel workflow that
      can operationalize them. Electronic chemotherapy roadmaps have been produced for
      36 treatment protocols, and 369 electronic chemotherapy roadmaps have been used
      for 352 pediatric oncology patients. They have functioned as designed and have
      not had any unintended effects. In the 5 years after their implementation, the
      average proportion of patient safety events involving paper or electronic
      chemotherapy roadmaps decreased by 78.7%. This report is the first to demonstrate
      the feasibility of creating and implementing electronic chemotherapy roadmaps.
      Continued expansion of the current library will be necessary to formally test the
      hypothesis that electronic chemotherapy roadmaps can decrease the risks
      associated with their paper counterparts and increase the safety of the
      chemotherapy process.

PMID- 29633659
TI  - Road to Home Program: A Performance Improvement Initiative to Increase Family and
      Nurse Satisfaction With the Discharge Education Process for Newly Diagnosed
      Pediatric Oncology Patients [Formula: see text].
AB  - Families of children, adolescents, and young adults with a new oncology diagnosis
      must absorb knowledge and skills needed to care for their child at home during a
      period of emergent hospitalizations and intense medical interventions. Effective
      nurse-led teaching and discharge planning begun at diagnosis can prepare families
      to safely care for their child following discharge, and be a source of
      satisfaction. The objective of this performance improvement initiative was to
      increase family and nurse satisfaction with new diagnosis education and
      discharge. Using standard performance improvement techniques, family and nursing
      stakeholder satisfaction with current processes was assessed. Working from
      established best practice and literature review; The Road to Home was designed
      and implemented. This novel, comprehensive program includes a visual, interactive
      display of required education based on the Children's Oncology Group Family
      Handbook(c) and hospital specific discharge materials; standardized teaching,
      tools and documentation for nursing; and caregiver discharge tool kits.
      Stakeholder input guided improvement strategies throughout the phases of
      implementation. Sustained increases in family and nurse satisfaction resulted
      from each phase. The Road to Home program is established for all families of
      newly diagnosed oncology patients and is meeting goals of increased family and
      nurse satisfaction with discharge education.

PMID- 29633660
TI  - IGRA-Based Screening for Latent Tuberculosis Infection in Persons Newly
      Incarcerated in New York City Jails.
AB  - In the United States, latent tuberculosis infection (LTBI) detection in
      correctional settings is a public health priority. Interferon gamma release assay
      (IGRA)-based LTBI screening was introduced in New York City jails in 2011 to
      2012, replacing historically used tuberculin skin testing (TST), which was
      associated with substantial incomplete screening rates. This retrospective, cross
      sectional study evaluated LTBI screening outcomes and correlates of positivity in
      40,986 persons newly incarcerated in 2011 to 2013. Of 35,090 eligible patients
      tested (96.4%), final results were 6.3% positive, 93.4% negative, and 0.2%
      indeterminate. In multivariable regression modeling, sex, age, race/ethnicity,
      nativity, marital status, prior jail incarceration, and HIV status were
      correlated with positivity. IGRA-based screening yielded high screening and low
      indeterminate test rates and may be recommended in correctional and other
      settings where TST is currently used.

PMID- 29633661
TI  - Commentary: Is Prophylactic Paving of Highly Calcified Femoropopliteal Occlusions
      All It's Cracked Up to Be?

PMID- 29633662
TI  - Commentary: Adapting Access Techniques to Cap Morphology to Enhance Successful
      Crossing of Chronic Total Occlusions: Tibiopedal Access Enters the Era of
      Revascularization Strategy.

PMID- 29633663
TI  - Contact to the out-of-hours service among Danish parents of small children - a
      qualitative interview study.
AB  - OBJECTIVE: In Denmark, parents with small children have the highest contact
      frequency to out-of-hours (OOH) service, but reasons for OOH care use are
      sparsely investigated. The aim was to explore parental contact pattern to OOH
      services and to explore parents' experiences with managing their children's acute
      health problems. DESIGN: A qualitative study was undertaken drawing on a
      phenomenological approach. We used semi-structured interviews, followed by an
      inductive content analysis. Nine parents with children below four years of age
      were recruited from a child day care centre in Aarhus, Denmark for interviews.
      RESULTS: Navigation, information, parental worry and parental development
      appeared to have an impact on OOH services use. The parents found it easy to
      navigate in the health care system, but they often used the OOH service instead
      of their own general practitioner (GP) due to more compatible opening hours and
      insecurity about the urgency of symptoms. When worried about the severity, the
      parents sought information from e.g. the internet or the health care
      professionals. The first child caused more worries and insecurity due to less
      experience with childhood diseases and the contact frequency seemed to decrease
      with parental development. CONCLUSION: Parents' use of the OOH service is
      affected by their health literacy levels, e.g. level of information, how easy
      they find access to their GP, how trustworthy and authorized health information
      is, as well as how much they worry and their parental experience. These findings
      must be considered when planning effective health services for young families.
      Key points The main findings are that the parents in our study found it easy to
      navigate in the healthcare system, but they used the OOH service instead of their
      own general practitioner, when this suited their needs. The parents sought
      information from e.g. the internet or the health care professionals when they
      were worried about the severity of their children's diseases. They sometimes
      navigated strategically in the healthcare system by e.g. using the OOH service
      for reassurance and when it was most convenient according to opening hours. The
      first child seemed to cause more worries and insecurity due to limited experience
      with childhood diseases, and parental development seems to decrease contact
      frequency. Overall, this study contributes with valuable insights into the
      understanding of parents' help seeking behaviour. There seems to be a potential
      for supporting especially first-time parents in their use of the out of hours
      services.

PMID- 29633664
TI  - Mean platelet volume at baseline and immune thrombocytopenia relapse in Chinese
      newly-diagnosed patients: a retrospective cohort study.
AB  - OBJECTIVE: In China, the ability of the current immune thrombocytopenia (ITP)
      guideline to stratify recurrent risk at diagnosis is limited. This study aimed to
      investigate whether mean platelet volume at diagnosis (MPV) is a risk factor for
      ITP relapse in Chinese. METHODS: The present study was a retrospective cohort
      study. Two hundred thirty-three adult patients with newly diagnosed ITP were
      consecutively and nonselectively collected from March 2013 to June 2017. The
      exposure and outcome variable were MPV at baseline and relapse-free survival at 6
      months. Other covariants included demographic data, general information,
      variables that can affect MPV reported by previous literature and risk factors of
      ITP relapse. RESULTS: After adjusting potential confounders, the non-linear
      relationship was detected between MPV and ITP relapse, and inflection point was
      21. The effect sizes and the confidence intervals on the left and right sides of
      inflection point were 1.30 (1.22-1.39) and 0.89 (0.76-1.04), respectively.
      Subgroup analysis showed, in subjects with hyperuricemia (1.54 (1.24, 1.90)), MPV
      showed significant differences from non-hyperuricemia (1.19 (1.13, 1.25)), and
      the p for interaction was less than 0.05. CONCLUSION: The relationship between
      MPV and ITP relapse is non-linear. MPV is an independent risk factor of ITP
      relapse when MPV is less than 21 fl.

PMID- 29633666
TI  - Impaired facial expression recognition in patients with social anxiety disorder:
      a case-control study.
AB  - INTRODUCTION: The aim of this study was to investigate whether social anxiety
      disorder (SAD) patients have low emotion recognition accuracy, take longer for
      emotion recognition and tended to interpret a stimulus more negatively than
      controls. METHODS: Fifty-six SAD patients and 56 healthy controls were
      participated in this study. We evaluated facial emotion recognition using a
      computer program in which participants chose one of seven emotions as displayed
      in each of 55 photographs of faces. We compared the accuracy and reaction times
      of the patients and controls. We further analysed which emotions were selected in
      the incorrect answers. RESULTS: SAD patients showed delayed reaction times for
      all emotions except anger and lower accuracy for fear, surprise, neutrality and
      happiness compared to controls. After applying Bonferroni correction, only
      delayed reaction time for surprise and happiness were remain significant.
      Neutrality was not mistaken for a negative emotion at a higher rate by SAD
      patients than by controls. CONCLUSION: This result suggests that the alterations
      of reaction time and accuracy of emotion recognition of SAD patients, especially
      in emotions with positive valence, play a more important role than negative bias
      in the cognitive aspects of SAD.

PMID- 29633667
TI  - Successful Use of Veno-Venous Extracorporeal Membrane Oxygenation in an Adult
      Patient with Sickle Cell Anemia and Severe Acute Chest Syndrome.
AB  - A 25-year-old female with sickle cell anemia presented with respiratory failure
      due to acute chest syndrome (ACS). Given her severely compromised cardiopulmonary
      status, she was started on veno-venous extracorporeal membrane oxygenation (VV
      ECMO). After 20 days, the patient's respiratory status improved and she was
      successfully decannulated. Veno-venous extracorporeal membrane oxygenation can be
      utilized for severe ACS in adult patients with sickle cell disease. Prompt
      initiation of this modality may improve outcomes in adult patients with sickle
      cell disease complicated by life threatening ACS.

PMID- 29633668
TI  - Left Ventricular Diastolic Dysfunction in beta-Thalassemia Major with Heart
      Failure.
AB  - We studied the clinical, electrocardiographic, echocardiographic, Doppler and T2*
      cardiac magnetic resonance (CMR) data of all adult beta-thalassemia major (beta
      TM) patients with heart failure (HF) consecutively observed at our referral
      center of the Sicilian region between 2008 and 2016. There were 16 patients
      enrolled in the study. Echocardiographic examination showed that only one patient
      had HF with systolic dysfunction of the left ventricle (HFrEF), whereas the
      others had HF with preserved systolic function of the left ventricle (HFpEF).
      Systolic dysfunction of the right ventricle (RV) was observed in 13 cases.
      Furthermore, 30.0% of the patients presented T2* CMR values consistent with
      intermediate risk of systolic dysfunction of the left ventricle (LV) due to iron
      overload, whereas 70.0% had normal values. Typical electrocardiographic
      abnormalities (wide T wave inversion and low voltages) were observed in 11 out of
      16 patients. In conclusion, in the adult beta-TM patients with HF recently
      observed at our center, the predominant form was that with diastolic dysfunction
      of the LV, and with systolic dysfunction of the RV. Only 30.0% had low values of
      T2* CMR. Typical electrocardiographic abnormalities were found in 69.0%.

PMID- 29633670
TI  - PREVALENCE OF CHILDHOOD OBESITY AND UNDERNUTRITION AMONG URBAN SCHOOL CHILDREN IN
      BANGLADESH.
AB  - SummaryDespite the ongoing problems of undernutrition and infectious disease,
      obesity and overweight have become a major problem in developing countries,
      including Bangladesh. This cross-sectional study was undertaken to determine the
      prevalence of obesity, overweight and underweight among school children aged 6-12
      years in Bangladesh. The study was conducted from June 2012 to May 2013 and the
      study sample comprised 1768 children (980 boys; 788 girls) from eight purposively
      selected schools in different areas of Dhaka city. Students were interviewed
      about their diet and physical activity, and anthropometric measurements were
      made, including height, weight, mid-upper-arm circumference (MUAC), waist
      circumference, hip circumference and body mass index (BMI). Undernutrition,
      overweight and obesity were defined using internationally accepted BMI cut-off
      points. Mean height, weight, BMI, MUAC, waist circumference and hip circumference
      values were found to be higher in boys than in girls, except at age 12 when these
      were found to be significantly higher in girls than in boys (p<0.05). The mean
      prevalence of overweight was 10.0% (boys 10.2%; girls 9.8%), and that of obesity
      5.0% (boys 4.3%; girls 5.8%). The prevalence of underweight was 16.3% in boys and
      12.7% in girls. The prevalence of underweight was significantly higher in poor
      than in rich children (22.1% vs 11.2%) and that of obesity was higher in rich
      than in poor children (9.9% vs 1.3%; p<0.001). A family history of obesity and
      hypertension emerged as a significant predictor of developing overweight and
      obesity (p<0.001). The data suggest that underweight and obesity co-exist in
      urban areas of Bangladesh, posing a challenge for the nutritional health of
      Bangladeshi children.

PMID- 29633671
TI  - REGIONAL DIFFERENCES IN POSITIVE SEXUAL BEHAVIOUR AMONG YOUTH IN SUB-SAHARAN
      AFRICA.
AB  - SummaryThe question of youth sexual behaviour has been widely debated, with
      researchers such as Berhan and Berhan (2015) arguing that young adults aged 15-24
      are more likely to engage in risky behaviours. However, research has not
      adequately addressed the issue of positive sexual behaviours, in particular among
      young people in sub-Saharan Africa. Adapting the compensatory model of risk and
      resiliency theory, this study examined the determinants of positive sexual
      behaviours among youth in sub-Saharan Africa. Using recent data from Demographic
      and Health Surveys of sixteen countries representative of each African region
      (East, West, Southern and Central), it was hypothesized that positive sexual
      behaviours of youth (condom use at last sex and single sexual partnership) would
      be most strengthened by protective factors at the individual and family levels,
      and that these behaviours would differ by region due to regional variation in
      socio-cultural practices. Delayed age at sexual debut (first sex after the age of
      15) was found to be the strongest protective factor for positive sexual
      behaviours among males and females in sub-Saharan Africa. Certain socioeconomic
      variables were found to be positively associated with positive sexual behaviours
      and the associations differed by gender.

PMID- 29633672
TI  - ETHICS EVALUATION REVEALING DECISION-MAKER MOTIVES: A CASE OF NEONATAL SCREENING.
AB  - OBJECTIVES: This paper aims to describe the added value of combining cost
      effectiveness and ethical evaluations when the preferences of the decision maker
      toward cost-effectiveness evaluation outcomes are not known, with the French
      national neonatal screening of cystic fibrosis (CF) as a case-study. METHODS: A
      cost-effectiveness analysis comparing four CF neonatal screening strategies, with
      or without DNA testing, was performed. Ethical positions toward their outcomes
      were described. In addition, a post-hoc analysis of the ethical issues being
      considered relevant from the decision-makers' perspective was conducted. RESULTS:
      Two strategies were found equally cost-effective. Among them, choosing the non
      DNA or a DNA-based strategy constrains the decision maker to render a judgement
      between different ethical issues or disagreements associated with the screening
      program. CONCLUSIONS: The analysis supports the relevance of combining cost
      effectiveness and ethics evaluation in developing health policy, as a way to
      reveal or clarify the motives associated with health. The choice of the decision
      maker to favor the DNA-based strategy, which was not originally recommended,
      creates the opportunity to make explicit the role played by ethical issues in the
      decision.

PMID- 29633673
TI  - DECISION-COMPONENTS OF NICE'S TECHNOLOGY APPRAISALS ASSESSMENT FRAMEWORK.
AB  - OBJECTIVES: Value assessment frameworks have gained prominence recently in the
      context of U.S. healthcare. Such frameworks set out a series of factors that are
      considered in funding decisions. The UK's National Institute of Health and Care
      Excellence (NICE) is an established health technology assessment (HTA) agency. We
      present a novel application of text analysis that characterizes NICE's Technology
      Appraisals in the context of the newer assessment frameworks and present the
      results in a visual way. METHODS: A total of 243 documents of NICE's medicines
      guidance from 2007 to 2016 were analyzed. Text analysis was used to identify a
      hierarchical set of decision factors considered in the assessments. The frequency
      of decision factors stated in the documents was determined and their association
      with terms related to uncertainty. The results were incorporated into visual
      representations of hierarchical factors. RESULTS: We identified 125 decision
      factors, and hierarchically grouped these into eight domains: Clinical
      Effectiveness, Cost Effectiveness, Condition, Current Practice, Clinical Need,
      New Treatment, Studies, and Other Factors. Textual analysis showed all domains
      appeared consistently in the guidance documents. Many factors were commonly
      associated with terms relating to uncertainty. A series of visual representations
      was created. CONCLUSIONS: This study reveals the complexity and consistency of
      NICE's decision-making processes and demonstrates that cost effectiveness is not
      the only decision-criteria. The study highlights the importance of processes and
      methodology that can take both quantitative and qualitative information into
      account. Visualizations can help effectively communicate this complex information
      during the decision-making process and subsequently to stakeholders.

PMID- 29633674
TI  - DIRECT COSTS OF TYPE 2 DIABETES: A BRAZILIAN COST-OF-ILLNESS STUDY.
AB  - OBJECTIVES: The aim of this study was to evaluate the direct costs of type 2
      diabetes mellitus patients treated in a Brazilian public hospital. METHODS: This
      was an exploratory retrospective cost-of-illness study with quantitative
      approach, using medical records of patients treated in a public hospital (2012
      14), with at least one consultation over a period of 12 months. Data on patient's
      profile, exams, number of consultations, medications, hospitalizations, and
      comorbidities were collected. The cost per patient per year (pppy) was calculated
      as well as the costs related to glycated hemoglobin (HbA1c) values, using
      thresholds of 7 and 8 percent. RESULTS: Data of 726 patients were collected with
      mean age of 62 +/- 11 years (68.3 percent female). A total of 67.1 percent
      presented HbA1c > 7 percent and 44.9 percent > 8 percent. The median cost of
      diabetes was United States dollar (USD) 197 pppy. The median costs of medication
      were USD 152.49 pppy, while costs of exams and consultations were USD 40.57 pppy
      and 8.70 pppy, respectively. Thirty-eight patients (4 percent) were hospitalized
      and presented a median cost of 3,656 per patient per hospitalization with a cost
      equivalent to 53.1 percent of total expenses. Total costs of patients with HbA1c
      <= 7 percent were lower for this group and also costs of medications and
      consultations, whereas for patients with HbA1c <= 8 percent, only total costs and
      costs of medications were lower when compared with HbA1c > 8 percent patients.
      CONCLUSIONS: Medications and hospitalizations were the major contributor of
      diabetes expenses. Preventing T2DM, or reducing its complications through
      adequate control, may help avoid the substantial costs related to this disease.

PMID- 29633675
TI  - CONSISTENCY OF THE EFFECTS OF FEMALE EDUCATION ON FERTILITY ACROSS THE NORTH
      SOUTH DEMOGRAPHIC DIVIDE IN NIGERIA, 2003-2013.
AB  - SummaryMost studies examining the association between female education and
      fertility have reported an inverse association. However, little is known about
      the consistency of the relationship, or what level of education triggers an
      inverse association. This study examined the consistency of the association
      between female education and fertility across the north-south demographic divide
      in Nigeria. Data on women aged 40-49 were taken from the 2003, 2008 and 2013
      Nigerian DHS data sets. The results showed that female education remained
      significantly and consistently inversely related to fertility in both the north
      and south of Nigeria. Women with secondary or higher level of education reported
      a lower number of children ever born (CEB) than those with primary or no
      education in both the north and south (p<0.05). The findings suggest that female
      education has a more effective negative effect on fertility in the south, where
      the level of female schooling is higher, than in the north, with its limited
      level of female education. Primary-level female education appeared to be
      ineffective in reducing fertility in the study sample. Women with primary
      schooling reported a slightly higher CEB than those who did not have any formal
      education. Also, age at marriage and child mortality were found to be consistent
      and significant predictors of fertility in both the north and south (p<0.001).
      Women who married at relatively higher ages and those who had never lost a child
      reported a smaller CEB consistently in both the north and south (p<0.001).
      Therefore, to attain sustainable fertility decline throughout Nigeria, it is
      imperative that policies aimed at increasing the prevalence and quality of female
      education are pursued, and there must be a focus on social, physical,
      environmental and cultural factors influencing age at marriage and child
      mortality.

PMID- 29633676
TI  - Waterborne Norovirus outbreak at a seaside resort likely originating from
      municipal water distribution system failure.
AB  - In May 2016 a Norovirus (NoV) gastroenteritis outbreak involved a high school
      class visiting a seaside resort near Taormina (Mascali, Sicily). Twenty-four
      students and a teacher were affected and 17 of them showed symptoms on the second
      day of the journey, while the others got ill within the following 2 days.
      Symptoms included vomiting, diarrhoea and fever, and 12 students required
      hospitalisation. Stool samples tested positive for NoV genome by Real-Time
      polymerase chain reaction assay in all 25 symptomatic subjects. The GII.P2/GII.2
      NoV genotype was linked to the outbreak by ORF1/ORF2 sequence analysis. The
      epidemiological features of the outbreak were consistent with food/waterborne
      followed by person-to-person and/or vomit transmission. Food consumed at a shared
      lunch on the first day of the trip was associated to illness and drinking un
      bottled tap water was also considered as a risk factor. The analysis of water
      samples revealed the presence of bacterial indicators of faecal contamination in
      the water used in the resort as well as in other areas of the municipal water
      network, linking the NoV gastroenteritis outbreak to tap water pollution from
      sewage leakage. From a single water sample, an amplicon whose sequence
      corresponded to the capsid genotype recovered from patients could be obtained.

PMID- 29633677
TI  - The interaction between monoamine oxidase A (MAOA) and childhood maltreatment as
      a predictor of personality pathology in females: Emotional reactivity as a
      potential mediating mechanism - ERRATUM.

PMID- 29633678
TI  - Predicting Suicidal Ideation in Adolescent Boys and Girls: The Role of
      Psychological Maturity, Personality Traits, Depression and Life Satisfaction.
AB  - In recent years, suicide rates have increased in adolescents and the young
      population, so these age groups are considered as populations at risk.
      Considering that suicidal ideation is the first sign of possible future suicide
      behavior, the objective of this study is to determine the relative importance of
      psychological maturity, personality, depression and life satisfaction in
      predicting suicidal ideation in adolescents. Results show that depressive
      symptoms is the variable that best predicts suicidal ideation, but psychological
      maturity, life satisfaction and emotional stability are predictors as well (R2 =
      .51, p < .001). However, the Multigroup Structural Equation Models analyses
      carried out show that emotional stability has an indirect relationship with
      suicidal ideation, through its relationship with depressive symptoms, life
      satisfaction and identity. Two Multigroup Structural Equation Models were
      proposed to better understand the relationships between these variables for each
      sex. The results show that the fit of the model that includes the variable Self
      reliance is better for boys than for girls (chi-square contributions of 8.175 for
      girls and 1.978 for boys) unlike the other model (chi-square contributions of
      0.288 for girls and 1.650 for boys). These results suggest that the psychological
      maturity subscale Self-reliance play a role in suicidal ideation in males but not
      in females. Although there have been no previous studies on the role of
      psychological maturity as a predictor of suicidal phenomena, the current study
      suggests that it is a feature to be considered in the prediction of adolescent
      suicidal ideation.

PMID- 29633679
TI  - Granulysin as a novel factor for the prognosis of the clinical course of
      chickenpox.
AB  - Granulysin is a recently discovered cytolytic protein of natural killer (NK)
      cells and cytotoxic T lymphocytes. Studies of healthy and immunocompromised
      patients with primary or recurrent varicella-zoster infections demonstrate the
      importance of virus-specific cellular immunity in controlling viral replication,
      but also some studies presented granulysin as a molecule that can play a role in
      chickenpox immunopathogenesis. This study investigated possible correlation
      between serum granulysin levels and clinical course of chickenpox. A total of 69
      patients with chickenpox were included in the study. We measured the levels of
      granulysin and percentage count for CD4+, CD8+ and NK cells in serum for all
      patients and healthy controls. For detection and quantification of granulysin in
      sera, we performed ELISA test and flow cytometry for detection, identification
      and percentage measurement of T and B lymphocytes. Descriptive methods, analysis
      of variance and multivariate logistic regression were used for statistical data
      analysis. We found respective correlation between serum granulysin level and
      severity of clinical presentation. These findings can be a good input for further
      studies, since there is no relevant prognostic parameter of chickenpox in
      everyday clinical practice. Granulysin, as a therapeutic, also deserves to be a
      point of interests in the future. If we prove its potential to stop dissemination
      of human herpes viruses, possibilities to use it in some life-threatening forms
      of viral disease can be very valuable.

PMID- 29633680
TI  - Antidepressant prescription rates and suicide attempt rates from 2004 to 2016 in
      a nationally representative sample of adolescents in the USA.

PMID- 29633681
TI  - Subjective wellbeing, suicide and socioeconomic factors: an ecological analysis
      in Hong Kong.
AB  - AIMS: There has recently been an increased interest in mental health indicators
      for the monitoring of population wellbeing, which is among the targets of
      Sustainable Development Goals adopted by the United Nations. Levels of subjective
      wellbeing and suicide rates have been proposed as indicators of population mental
      health, but prior research is limited. METHODS: Data on individual happiness and
      life satisfaction were sourced from a population-based survey in Hong Kong
      (2011). Suicide data were extracted from Coroner's Court files (2005-2013). Area
      characteristic variables included local poverty rate and four factors derived
      from a factor analysis of 21 variables extracted from the 2011 census. The
      associations between mean happiness and life satisfaction scores and suicide
      rates were assessed using Pearson correlation coefficient at two area levels: 18
      districts and 30 quantiles of large street blocks (LSBs; n = 1620). LSB is a
      small area unit with a higher level of within-unit homogeneity compared with
      districts. Partial correlations were used to control for area characteristics.
      RESULTS: Happiness and life satisfaction demonstrated weak inverse associations
      with suicide rate at the district level (r = -0.32 and -0.36, respectively) but
      very strong associations at the LSB quantile level (r = -0.83 and -0.84,
      respectively). There were generally very weak or weak negative correlations
      across sex/age groups at the district level but generally moderate to strong
      correlations at the LSB quantile level. The associations were markedly attenuated
      or became null after controlling for area characteristics. CONCLUSIONS:
      Subjective wellbeing is strongly associated with suicide at a small area level;
      socioeconomic factors can largely explain this association. Socioeconomic factors
      could play an important role in determining the wellbeing of the population, and
      this could inform policies aimed at enhancing population wellbeing.

PMID- 29633682
TI  - Children of parents who have been hospitalised with psychiatric disorders are at
      risk of poor school readiness.
AB  - AIMS: Children of parents with psychiatric disorders are at risk of poor
      outcomes. However, there is limited evidence regarding the relationship between
      parental psychiatric disorders and child school readiness, which is linked to
      later academic achievement. This study aims to investigate these relationships
      and broaden the evidence underlying the rationale for family-focused
      interventions for parental psychiatric disorders. METHOD: This study used linked
      administrative data. Children's school readiness in multiple developmental
      domains (physical, social, emotional, communicative, cognitive) was measured by
      the Australian Early Development Census (AEDC) for 19 071 Western Australian
      children (mean age 5.5 years). Children scoring in the bottom 25% on any AEDC
      domain were considered developmentally vulnerable, or at risk of vulnerability,
      on that domain. Biological child-parent pairs were identified using birth
      records. Parents with psychiatric disorders were identified from hospital
      records, which included information on diagnosis and frequency/duration of
      psychiatric admissions. Logistic regressions, adjusted for parent age, mother's
      marital status, child Aboriginality, child English language status, local
      community remoteness and socioeconomic index, estimated the odds of children
      being vulnerable/at-risk on each of the AEDC domains. RESULTS: A total of 719
      mothers and 417 fathers had a psychiatric hospitalisation during the study period
      (12 months prior to the child's birth, up to the end of 2009). Children whose
      parents had psychiatric disorders had increased odds of being classified as
      vulnerable/at-risk for school readiness. This increase in odds was evident for
      both maternal (adjusted odds ratio, aOR 1.37- 1.51) and paternal psychiatric
      disorders (aOR 1.38-1.50); and for a single admission of one day (aOR 1.32-1.59),
      a single admission of multiple days (aOR 1.30-1.47), and multiple admissions (aOR
      1.35-1.63). Some variability in child outcome was found depending on the parents'
      psychiatric diagnosis (mood, anxiety, substance abuse or comorbid disorder).
      CONCLUSIONS: Children of parents who have been hospitalised with psychiatric
      disorders are at risk for poor school readiness. These findings add support to
      recommendations that mental health professionals consider dependent children in
      discharge and treatment planning for adult psychiatric inpatients. It is also
      important to ensure that the impact of psychiatric illness in fathers is not
      overlooked in assessment and intervention. Family-based approaches to adult
      psychiatric care could meet the dual needs of intervention for parents and
      preventative measures for children. These findings can inform policy regarding
      the importance of integrating and coordinating services to meet the needs of
      families.

PMID- 29633683
TI  - Bovine herpes virus type-4 infection among postpartum dairy cows in California:
      risk factors and phylogenetic analysis.
AB  - The aims of this study were to determine the prevalence and associated risk
      factors of bovine herpes virus type-4 (BoHV-4) infection and describe the genetic
      characteristics and predominant genotypes of the virus in Yolo and Tulare
      counties, California. A cross-sectional study involving multi-stage sampling
      technique was used. One hundred and forty-eight post-partum cows were enrolled
      from 11 dairy farms. Uterine/vaginal samples were collected and tested for BoHV-4
      and other co-infecting viruses using real-time PCR. Data were analysed using
      multilevel logistic mixed-effect model. Phylogenetic analysis of 10 BoHV-4
      isolates was conducted by targeting three open reading frames (ORF3, ORF8 and ORF
      22) of the viral genome. The prevalence of BoHV-4 infection was 22.3% (33/148),
      while post-partum metritis was 33.8% (48/142). Strong association was found
      between BoHV-4 infection and lactation number, lactation stage and post-partum
      metritis. The odds of being positive for BoHV-4 infection were 6.47 times (95% CI
      1.17-35.92; P 240 days). Cows with post-partum metritis were 4.51 times (95% CI
      1.27-16.02; P < 0.05) more likely to test positive for BoHV-4 infection compared
      with those without post-partum metritis. Phylogenetic analysis of BoHV-4 based on
      sequencing of glycoprotein and thymidine kinase (TK) genes revealed genetic
      variability of the virus with glycoprotein B genotype 1 and TK genotype 2 as
      being dominant genotypes. The reported high genetic variability of BoHV-4
      indicates the possibility of co-infection with multiple genotypes.

PMID- 29633684
TI  - Portuguese Norms of Name Agreement, Concept Familiarity, Subjective Frequency and
      Visual Complexity for 150 Colored and Tridimensional Pictures.
AB  - Pictures are complex stimuli that require a careful control of several
      characteristics and attributes standardized for different languages. In this work
      we present for the first time European Portuguese (EP) norms for name agreement,
      concept familiarity, subjective frequency and visual complexity for a new set of
      150 colored pictures. These pictures were selected to represent exemplars of the
      most used semantic categories in research and to depict objects which, though
      familiar to the participants, were rarely used in daily life, which makes them
      particularly prone to speech failures such as tip-of-the-tongue (TOT) states.
      Norms were collected from 640 EP native speakers that rated each picture in the
      four variables through a web-survey procedure. Results showed, as expected, that
      a large number of pictures in the dataset elicited a TOT response, and
      additionally that the ratings obtained in each of the dimensions are in line with
      those observed in other pictorial datasets. Norms can be freely downloaded at
      https://www.psi.uminho.pt/en/Research/Psycholinguistics/Pages/Databases.aspx.

PMID- 29633685
TI  - Bayesian evidence and epidemiological implications of environmental contamination
      from acute respiratory infection in long-term care facilities.
AB  - Skilled nursing home facilities (SNFs) house a vulnerable population frequently
      exposed to respiratory pathogens. Our study aims to gain a better understanding
      of the transmission of nursing home-acquired viral respiratory infections in non
      epidemic settings. Symptomatic surveillance was performed in three SNFs for
      residents exhibiting acute respiratory symptoms. Environmental surveillance of
      five high-touch areas was performed to assess possible transmission. All resident
      and environmental samples were screened using a commercial multiplex polymerase
      chain reaction platform. Bayesian methods were used to evaluate environmental
      contamination. Among nursing home residents with respiratory symptoms, 19% had a
      detectable viral pathogen (parainfluenza-3, rhinovirus/enterovirus, RSV, or
      influenza B). Environmental contamination was found in 20% of total room surface
      swabs of symptomatic residents. Environmental and resident results were all
      concordant. Target period prevalence among symptomatic residents ranged from 5.5
      to 13.3% depending on target. Bayesian analysis quantifies the probability of
      environmental shedding due to parainfluenza-3 as 92.4% (95% CI: 86.8-95.8%) and
      due to rhinovirus/enterovirus as 65.6% (95% CI: 57.9-72.5%). Our findings confirm
      that non-epidemic viral infections are common among SNF residents exhibiting
      acute respiratory symptoms and that environmental contamination may facilitate
      further spread with considerable epidemiological implications. Findings further
      emphasise the importance of environmental infection control for viral respiratory
      pathogens in long-term care facilities.

PMID- 29633686
TI  - Giardia and Cryptosporidium antibody prevalence and correlates of exposure among
      Alaska residents, 2007-2008.
AB  - Giardia duodenalis and Cryptosporidium spp. are common intestinal protozoa that
      can cause diarrhoeal disease. Although cases of infection with Giardia and
      Cryptosporidium have been reported in Alaska, the seroprevalence and correlates
      of exposure to these parasites have not been characterised. We conducted a
      seroprevalence survey among 887 residents of Alaska, including sport hunters,
      wildlife biologists, subsistence bird hunters and their families and non-exposed
      persons. We tested serum using a multiplex bead assay to evaluate antibodies to
      the Giardia duodenalis variant-specific surface protein conserved structural
      regions and to the Cryptosporidium parvum 17- and 27-kDa antigens. Approximately
      one third of participants in each group had evidence of exposure to
      Cryptosporidium. Prevalence of Giardia antibody was highest among subsistence
      hunters and their families (30%), among whom positivity was associated with lack
      of community access to in-home running water (adjusted prevalence ratio [aPR]
      1.15, 95% confidence interval (CI) 1.02-1.28) or collecting rain, ice, or snow to
      use as drinking water (aPR 1.09, 95% CI 1.01-1.18). Improving in-home water
      access for entire communities could decrease the risk of exposure to Giardia.

PMID- 29633687
TI  - Validation Evidence of the Motivation for Teaching Scale in Secondary Education.
AB  - Grounded in self-determination theory, the aim of this study was to develop a
      scale with adequate psychometric properties to assess motivation for teaching and
      to explain some outcomes of secondary education teachers at work. The sample
      comprised 584 secondary education teachers. Analyses supported the five-factor
      model (intrinsic motivation, identified regulation, introjected regulation,
      external regulation and amotivation) and indicated the presence of a continuum of
      self-determination. Evidence of reliability was provided by Cronbach's alpha,
      composite reliability and average variance extracted. Multigroup confirmatory
      factor analyses supported the partial invariance (configural and metric) of the
      scale in different sub-samples, in terms of gender and type of school. Concurrent
      validity was analyzed by a structural equation modeling that explained 71% of the
      work dedication variance and 69% of the boredom at work variance. Work dedication
      was positively predicted by intrinsic motivation (beta = .56, p < .001) and
      external regulation (beta = .29, p < .001) and negatively predicted by
      introjected regulation (beta = -.22, p < .001) and amotivation (beta = -.49, p <
      .001). Boredom at work was negatively predicted by intrinsic motivation (beta = 
      .28, p < .005) and positively predicted by amotivation (beta = .68, p < .001).
      The Motivation for Teaching Scale in Secondary Education (Spanish acronym EME-ES,
      Escala de Motivacion por la Ensenanza en Educacion Secundaria) is discussed as a
      valid and reliable instrument. This is the first specific scale in the work
      context of secondary teachers that has integrated the five-factor structure
      together with their dedication and boredom at work.

PMID- 29633688
TI  - Brain structural covariance network centrality in maltreated youth with PTSD and
      in maltreated youth resilient to PTSD.
AB  - Child maltreatment is a major cause of pediatric posttraumatic stress disorder
      (PTSD). Previous studies have not investigated potential differences in network
      architecture in maltreated youth with PTSD and those resilient to PTSD. High
      resolution magnetic resonance imaging brain scans at 3 T were completed in
      maltreated youth with PTSD (n = 31), without PTSD (n = 32), and nonmaltreated
      controls (n = 57). Structural covariance network architecture was derived from
      between-subject intraregional correlations in measures of cortical thickness in
      148 cortical regions (nodes). Interregional positive partial correlations
      controlling for demographic variables were assessed, and those correlations that
      exceeded specified thresholds constituted connections in cortical brain networks.
      Four measures of network centrality characterized topology, and the importance of
      cortical regions (nodes) within the network architecture were calculated for each
      group. Permutation testing and principle component analysis method were employed
      to calculate between-group differences. Principle component analysis is a
      methodological improvement to methods used in previous brain structural
      covariance network studies. Differences in centrality were observed between
      groups. Larger centrality was found in maltreated youth with PTSD in the right
      posterior cingulate cortex; smaller centrality was detected in the right inferior
      frontal cortex compared to youth resilient to PTSD and controls, demonstrating
      network characteristics unique to pediatric maltreatment-related PTSD. Larger
      centrality was detected in right frontal pole in maltreated youth resilient to
      PTSD compared to youth with PTSD and controls, demonstrating structural
      covariance network differences in youth resilience to PTSD following
      maltreatment. Smaller centrality was found in the left posterior cingulate cortex
      and in the right inferior frontal cortex in maltreated youth compared to
      controls, demonstrating attributes of structural covariance network topology that
      is unique to experiencing maltreatment. This work is the first to identify
      cortical thickness-based structural covariance network differences between
      maltreated youth with and without PTSD. We demonstrated network differences in
      both networks unique to maltreated youth with PTSD and those resilient to PTSD.
      The networks identified are important for the successful attainment of age
      appropriate social cognition, attention, emotional processing, and inhibitory
      control. Our findings in maltreated youth with PTSD versus those without PTSD
      suggest vulnerability mechanisms for developing PTSD.

PMID- 29633689
TI  - A Comparison of Patients' Local Conceptions of Illness and Medicines in the
      Context of C-Reactive Protein Biomarker Testing in Chiang Rai and Yangon.
AB  - Antibiotic resistance is not solely a medical but also a social problem,
      influenced partly by patients' treatment-seeking behavior and their conceptions
      of illness and medicines. Situated within the context of a clinical trial of C
      reactive protein (CRP) biomarker testing to reduce antibiotic over-prescription
      at the primary care level, our study explores and compares the narratives of 58
      fever patients in Chiang Rai (Thailand) and Yangon (Myanmar). Our objectives are
      to 1) compare local conceptions of illness and medicines in relation to health
      care seeking and antibiotic demand; and to 2) understand how these conceptions
      could influence CRP point-of-care testing (POCT) at the primary care level in low
      and middle-income country settings. We thereby go beyond the current knowledge
      about antimicrobial resistance and CRP POCT, which consists primarily of clinical
      research and quantitative data. We find that CRP POCT in Chiang Rai and Yangon
      interacted with fever patients' preexisting conceptions of illness and medicines,
      their treatment-seeking behavior, and their health-care experiences, which has
      led to new interpretations of the test, potentially unforeseen exclusion
      patterns, implications for patients' self-assessed illness severity, and an
      increase in the status of the formal health-care facilities that provide the
      test. Although we expected that local conceptions of illness diverge from inbuilt
      assumptions of clinical interventions, we conclude that this mismatch can
      undermine the intervention and potentially reproduce problematic equity patterns
      among CRP POCT users and nonusers. As a partial solution, implementers may
      consider applying the test after clinical examination to validate rather than
      direct prescription processes.

PMID- 29633690
TI  - Genomic Characterization and Seroprevalence Studies on Alphaviruses in Uruguay.
AB  - Alphaviruses (Togaviridae) are arboviruses frequently associated with emerging
      infectious diseases. In this study, we aimed to investigate the presence of
      alphaviruses in Uruguay by detecting the viral genome in mosquitoes and
      neutralizing antibodies in equines. A total of 3,575 mosquitoes were analyzed for
      alphavirus genome detection. Serologic studies were performed on 425 horse sera
      by plaque reduction neutralization test (PRNT80) against Venezuelan equine
      encephalitis virus (VEEV) subtype IAB, Pixuna virus (PIXV), Rio Negro virus
      (RNV), western equine encephalitis virus (WEEV), and Madariaga virus (MADV).
      Mosquitoes belonging to six genera were captured and 82.9% were identified as
      Culex pipiens. Two Cx. pipiens pools collected in Fray Bentos and Las Toscas
      localities were alphavirus positive, and phylogenetic analyses showed that the
      sequences grouped into two different clusters: the lineage I of eastern equine
      encephalitis virus and RNV (VEEV complex), respectively. Plaque reduction
      neutralization test assays showed antibodies against strains of the VEEV complex,
      MADV, and WEEV. Rio Negro virus was the most geographically widespread virus,
      showing higher seroprevalences (up to 20%). Seroprevalences against VEEV IAB
      ranged between 4.6% and 13%; antibodies against PIXV, WEEV, and MADV were less
      frequent (3-4%). In conclusion, RNV exhibited the highest seroprevalence in
      horses, a wide geographical distribution, and viral genome was detected in Cx.
      pipiens mosquitoes. Madariaga virus had a low seroprevalence in equines, but an
      epizootic lineage typical of North America was detected in Cx. pipiens
      mosquitoes. Taken together, our results show that alphaviruses are present in
      Uruguay with variable occurrence and geographical distribution being a potential
      threat for human and equine health.

PMID- 29633691
TI  - Mechanical thrombectomy for acute ischemic stroke: the therapeutic window is
      larger but still "time is brain".

PMID- 29633692
TI  - Pharmacological differences and clinical implications of various botulinum toxin
      preparations: a critical appraisal.
AB  - Three different type A botulinum neurotoxins (BoNTAs) - onabotulinumtoxinA,
      abobotulinumtoxinA and incobotulinumtoxinA) - are currently marketed in Europe to
      treat several conditions. Differences between BoNTA preparations, which depend on
      their specific biotypes and manufacturing processes, lead to clinically relevant
      pharmacotherapeutic dissimilarities. All three available products are separately
      recognized and reviewed in American Academy of Neurology guidelines. The
      neurotoxin load/100U is likewise different among the different BoNTAs, with the
      result that the specific potency of the 150kD BoNTA neurotoxin is calculated as
      137 units/ng for onabotulinumtoxinA, 154 units/ng for abobotulinumtoxinA, and 227
      units/ng for incobotulinumtoxinA. It is important for clinicians to have all
      three BoNTAs available in order to choose the most suitable preparation for the
      specific indication in the single patient. Commercially available BoNTAs must be
      recognized as different from one another, and therefore as non-interchangeable.
      The essential experience of the clinician is of the utmost importance in choosing
      the most appropriate treatment.

PMID- 29633693
TI  - Multicentre registry of brain-injured patients with disorder of consciousness:
      rationale and preliminary data.
AB  - Diagnostic accuracy and reliable estimation of clinical evolution are challenging
      issues in the management of patients with disorders of consciousness (DoC).
      Longitudinal systematic investigations conducted in large cohorts of patients
      with DoC could make it possible to identify reliable diagnostic and prognostic
      markers. On the basis of this consideration, we devised a multicentre prospective
      registry for patients with DoC admitted to ten intensive rehabilitation units.
      The registry collects homogeneous and detailed data on patients' demographic and
      clinical features, neurophysiological and neuroimaging findings, and medical and
      surgical complications. Here we present the rationale and the design of the
      registry and the preliminary results obtained in 53 patients with DoC (vegetative
      state or minimally conscious state) enrolled during the first seven months of the
      study. Data at 6-month post-injury follow-up were available for 46 of them. This
      registry could be an important tool for collecting high-quality data through the
      application of rigorous methods, and it could be used in the routine management
      of patients with DoC admitted to rehabilitation settings.

PMID- 29633694
TI  - Apathy in Parkinson's disease: differences between caregiver's report and self
      evaluation.
AB  - Apathy is a state of diminished goal-directed speech, motor activity and
      emotions. The prevalence of apathy in Parkinson's disease (PD) ranges from 16 to
      62%. Several studies have investigated the relationships between apathy and other
      dimensions of PD, but little is known about possible discrepancies between self
      evaluation (SE) and caregiver reporting (CR) of this symptom. The aim of this
      study is twofold: 1) to investigate the differences in apathy evaluations
      according to the point of view from which apathy is reported (SE vs CR); 2) to
      identify the possible relationships between each of the two evaluations (SE and
      CR) and cognitive and affective dimensions of PD. Forty-eight patients with PD
      were assessed using the Apathy Evaluation Scale (AES) in its SE and CR versions
      (AES-SE and AES-CR); cognitive, affective and behavioral symptoms were also
      assessed. AES-SE scores were significantly higher than AESCR ones. Neither AES
      version correlated with depression, whereas both correlated with motor
      impairment, disease stage and behavioral symptoms. Mini-Mental State Examination
      and Frontal Assessment Battery scores showed significant negative correlations
      only with AES-SE scores. Our findings suggest that the point of view from which
      apathy is seen can lead to significant discrepancies, even when using the same
      tool. This should be taken into account in order to obtain correct assessment of
      this disabling and distressing symptom.

PMID- 29633695
TI  - Management of spasticity with onabotulinumtoxinA: practical guidance based on the
      italian real-life post-stroke spasticity survey.
AB  - The present paper provides practical guidance on the management of adult
      spasticity with OnabotulinumtoxinA. Advisory Board members reviewed the available
      evidence and discussed their personal experiences in order to address the unmet
      needs in the management of spasticity with botulinum toxin type A identified by
      the recent Italian Real-Life Post-Stroke Spasticity Survey. Stroke patients
      should be referred to spasticity services that have adequate facilities and
      multidisciplinary teams with the necessary training, competence and expertise.
      The current literature shows a strong correlation between the development of post
      stroke spasticity and the degree of central sensorimotor system
      destruction/disorganization. Use of tools such as the Poststroke Checklist may
      help clinicians in the long-term follow-up of stroke patients. The maximum dose
      of onabotulinumtoxinA - according to the current literature this ranges from 300U
      to 400U for upper limb and from 500U to 600U for lower limb aggregate postures -
      should be re-considered. In addition, there is a need for future consensus (also
      based on pharmacoeconomic considerations) on consistent clinical care models for
      the management of patients with post-stroke spasticity.

PMID- 29633696
TI  - A role for accelerometry in the differential diagnosis of tremor syndromes.
AB  - Accelerometry is a reliable tool for gauging the occurrence, amplitude and
      frequency of tremor. However, there is no consensus on criteria for
      accelerometric diagnosis of tremor syndromes. We enrolled 20 patients with
      essential tremor (ET), 20 with dystonic tremor (DT), and 20 with classic
      parkinsonian tremor (PD-T), all meeting accepted clinical criteria. All the
      patients underwent dopamine transporter imaging (by means of single-photon
      emission computed tomography) and triaxial accelerometric tremor analysis. The
      latter revealed groupwise differences in tremor frequency, peak dispersion,
      spectral coherence, unilaterality and resting vs action tremor amplitude. From
      the above, five diagnostic criteria were extrapolated for each condition.
      Receiver operating characteristic curves, depicting criteriabased scoring of each
      tremor type, showed negligible declines in specificity for scores >=4 in patients
      with ET or DT and scores >=3 in patients with PD-T, thus providing a simple
      scoring method (accelerometrically derived) for differential diagnosis of the
      principal tremor syndromes.

PMID- 29633697
TI  - Effectiveness of a digital platform for sharing knowledge on headache management:
      a two-year experience.
AB  - It is crucial that all headache specialists receive adequate training.
      Considering the unsatisfactory results obtained with standard updating courses
      and the growing need for continuing professional education, a digital platform
      was developed as a training tool. The platform has been active since 1 October
      2014. It is readily accessible to doctors by free registration. Users have access
      to all the material available on the platform, which includes scientific
      articles, e-books, presentations and images. Users can share their own material
      and clinical cases directly. At the time of this study, the platform had 37
      users. In the second year following its launch 316 files were downloaded and five
      discussions were started. These saw 22 contributions. Fifteen of the 37 members
      did not perform any action on the platform. In total, 74 files were uploaded in
      the second year of activity, but 90% of the contributions came from a very small
      group of users. There were no significant differences in use of the platform
      between members of the Italian Society for the Study of Headache and other
      specialists. Even though the platform appears to be an easily accessible,
      interactive and inexpensive instrument, the higher number of downloads than
      uploads suggests that it is used passively.

PMID- 29633698
TI  - If you want to understand what it really means to live with cluster headache,
      imagine... fostering empathy through European patients' own stories of their
      experiences.
AB  - Cluster headache (CH) is arguably the most severe pain condition that afflicts
      humans. The severity of the pain has earned it the nickname "suicide headache".
      Understanding how CH impacts on those who suffer from it is essential, because
      this understanding creates empathy, which is so valuable to these patients. On
      the occasion of Cluster Headache Day 2017, we asked CH patients from different
      European countries to share their experiences, in order to help people to imagine
      what it means to live with the condition. Here, we look at some extracts from
      their stories. These CH patients' direct accounts provide an important
      illustration of the clinical features and consequences of the disease, helping to
      contextualise it and its psychological and social consequences. Reports of CH
      patients' first-person accounts might help to underline the physicians' role and
      responsibility with regard to the psychological and social consequences of this
      disease.

PMID- 29633700
TI  - Optimizing renal replacement therapy deliverables through multidisciplinary work
      in the intensive care unit.

PMID- 29633701
TI  - Challenges of performing renal replacement therapy in the intensive care unit -
      The nephrologist perspective.

PMID- 29633699
TI  - Pharmacokinetics of immediate release, extended release, and gastric retentive
      gabapentin formulations in healthy adults?.
AB  - OBJECTIVE: Gabapentin immediate release (GBP-IR), gabapentin gastric retentive
      (GBP-GR), and the prodrug gabapentin enacarbil extended release formulation (GEn)
      have been approved for management of postherpetic neuralgia (PHN) in adults. This
      is the first pharmacokinetic (PK) comparison of all three formulations using FDA
      recommended doses for PHN. MATERIALS: This study compared the steady-state PK of
      GBP-IR 600 mg t.i.d., GBP-GR 1,800 mg q.d., and GEn 600 mg b.i.d. in healthy
      adults. METHODS: The open-label study consisted of a 3-day lead-in of escalating
      doses of GBP-IR, 5 days of treatment with each formulation (GPB-IR, GPB-GR, and
      GEn), and a 7-day taper period on 600 mg GEn q.d.. Plasma concentrations were
      collected on day 5 for each formulation. PK parameters were estimated from plasma
      concentration data. RESULTS: 14 healthy subjects (7 men, 7 women; mean (SD) age,
      46.8 (7.60) years; mean (SD) body mass index, 26.7 (1.7) kg/m<sup>2</sup>)
      received all doses and completed the study. GBP-GR resulted in substantially (~ 4
      fold) higher peak-to-trough ratio and percent fluctuation compared to GEn. GEn
      resulted in more sustained and less fluctuating daily exposure relative to GBP
      IR, particularly at the end of 24 hours of dosing. In contrast, gabapentin
      fluctuation from GBP-IR consisted of 3 distinct peaks. After dose normalization,
      gabapentin exposure with GEn was ~ 2.2-fold and ~ 1.4-fold higher compared to GBP
      GR and GBP-IR, respectively. All treatments were well tolerated. CONCLUSION: GEn
      requires less frequent dosing compared with GBP-IR and fluctuates less with
      sustained gabapentin exposure throughout the day. These PK differences may have
      clinically relevant implications.?.

PMID- 29633702
TI  - Challenges of performing renal replacement therapy in the intensive care unit -
      The intensivist perspective.

PMID- 29633703
TI  - Proteinuria: A presenting manifestation of mirror syndrome in pregnancy?.
AB  - Hypertension and proteinuria in pregnant women are most commonly signs of
      preeclampsia which develops after 20 weeks of gestation. There are rare
      incidences of uncontrolled hypertension and nephrotic range proteinuria even in
      the first trimester of pregnancy which can be indicators of severe underlying
      fetal and placental abnormalities rather than preeclampsia. A G2P0 30-year-old
      Caucasian woman was admitted to University Hospital for the incidental finding of
      severe hypertension and proteinuria during her regular prenatal checkup at 14
      weeks. She had complaints of mild bifrontal headache, facial and lower extremity
      edema. Her admission blood pressure was 193/108 mmHg, she had 8 g proteinuria,
      normal creatinine, and negative immunological and infectious workup. Further
      evaluation with dedicated obstetric ultrasonography showed hydropic placenta and
      fetus with aneuploidy. These findings strengthened the suspicion for a rare
      disease process called mirror syndrome, and emergent delivery was done to treat
      maternal disease process. Mirror syndrome is a rare disease that occurs basically
      due to fetal/placental pathology. It can present at any gestational period, and
      the clinical features include edema, proteinuria, and hypertension, mimicking
      preeclampsia. Prompt diagnosis and treatment is very crucial to prevent maternal
      complications.?.

PMID- 29633704
TI  - Diastolic blood pressure variability in 24 hour-ABPM and outcomes of chronic
      kidney disease?.
AB  - BACKGROUND: Blood pressure variability (BPV) has been associated with increased
      morbidity and mortality. There are a few studies that reported worse outcomes of
      chronic kidney disease (CKD) with greater visit-to-visit BPV (VVV), but data with
      ambulatory blood pressure monitoring (ABPM) is scarce. MATERIALS AND METHODS:
      Ambulatory hypertensive CKD (stage 2 - 4) patients (> 18 years old) with complete
      24 hours of ABPM study (SpaceLabs), who were followed up between January 2012 and
      December 2016, were retrospectively analyzed for the baseline characteristics and
      outcomes of CKD. Coefficient of variation (CV) in diastolic blood pressure (DBP)
      was used as an index of BPV. RESULTS: Data of 191 patients (mean age 59.7 +/-
      12.4 years, 54.9% males, 42.1% diabetic, mean eGFR-EPI (Chronic Kidney Disease
      Epidemiology Collaboration) 51.7 +/- 22.0 mL/min/1.73m2, mean follow-up 26.2 +/-
      10.4 months) were available for the analysis. On multivariate linear regression
      analysis, greater DBP-CV was associated with slower decline in eGFR-EPI per year
      (B -0.648, p = 0.000). Likewise, the hazard ratio (HR) for dialysis inception
      (occurred in 9.4%) was found significantly lower with increasing DBP-CV in
      unadjusted and fully adjusted Cox models (HR 0.730, 95% CI 0.618 - 0.861, p =
      0.000, and HR 0.678, 95% CI 0.526 - 0.874, p = 0.003, respectively). CONCLUSION:
      These findings suggest that DBP variability in 24-hour ABPM may be a good
      prognostic factor for the outcomes of CKD. Further studies are needed to
      determine the impact of 24-hour ABPM BPV on CKD progression and its differences
      from VVV.?.

PMID- 29633705
TI  - Early postoperative measurement of fibroblast growth factor 23 predicts severe
      acute kidney injury in infants after cardiac surgery?.
AB  - AIMS: Acute kidney injury (AKI) occurs in 30 - 40% of children after cardiac
      surgery (CS) and is associated with poor prognosis. Fibroblast growth factor 23
      (FGF23) is a bone-derived hormone with a pivotal role in phosphorus and vitamin D
      metabolism. We assessed FGF23 as an early marker for severe AKI (sAKI) in infants
      after CS. MATERIALS AND METHODS: Samples were previously collected in a
      multicenter observational study from children after CS. Serum FGF23 (n = 41) and
      urine AKI biomarker levels (n = 35) were assessed 4 - 8 hours after bypass. sAKI
      was defined as >= 100% rise in serum creatinine over baseline. Non-parametric and
      ROC analyses were used to evaluate the association between FGF23, urine AKI
      markers, and sAKI in the week after CS. RESULTS: Serum FGF23, urine NGAL, and
      urine KIM1 were higher in sAKI patients. The AUC-ROC for urine NGAL (0.74, [0.49 
      0.99]), urine KIM1 (0.79, [0.68 - 0.98]), and serum FGF23 (0.74, [0.5 - 0.9])
      showed fair prediction of sAKI. CONCLUSION: Early measurement of FGF23 has
      predictive ability in infants who develop sAKI after CS with cardiopulmonary
      bypass.?.

PMID- 29633706
TI  - A preliminary survey of Trichinella spp. in pigs raised under controlled housing
      conditions in Colombia: 2014-2016.
AB  - A preliminary survey of Trichinella spp. infection was conducted in Colombian
      swine herds between 2014 and 2016. A total of 1,773 pigs reared on farms under
      controlled housing conditions and processed in 34 slaughterhouses were tested
      either by the artificial digestion of pooled muscle samples (n = 1,173) or by
      serology (n = 600). In addition, 550 rats trapped on 29 swine farm premises were
      also tested by artificial digestion. No positive pig samples were detected.
      Similarly, no Trichinella spp. muscle larvae were detected in rats. These results
      are in agreement with the lack of historical Trichinella infection reports in
      domestic and wild animals and humans in Colombia. However, a more extensive
      epidemiological investigation and a continuous surveillance program are needed to
      continue declaring swine herds in Colombia free of Trichinella infection.

PMID- 29633707
TI  - A tripartite survey of hyperparasitic fungi associated with ectoparasitic flies
      on bats (Mammalia: Chiroptera) in a neotropical cloud forest in Panama.
AB  - The Darien province in eastern Panama is one of the most unexplored and
      biodiverse regions in the world. The Chucanti Nature Reserve, in Serrania de
      Maje, consists of a diverse tropical cloud forest ecosystem. The aim of this
      research was to explore and study host associations of a tripartite system of
      bats, ectoparasitic flies on bats (Diptera, Streblidae), and ectoparasitic fungi
      (Ascomycota, Laboulbeniales) that use bat flies as hosts. We captured bats at
      Chucanti, screened each bat for presence of bat flies, and screened collected bat
      flies for presence of Laboulbeniales. We mistnetted for 68 mistnet hours and
      captured 227 bats representing 17 species. We captured Micronycteris schmidtorum,
      a species previously unreported in Darien. In addition, we encountered the rarely
      collected Platyrrhinus dorsalis, representing the westernmost report for this
      species. Of all captured bats, 148 carried bat flies (65%). The number of sampled
      bat flies was 437, representing 16 species. One species represents a new country
      record (Trichobius anducei) and five species represent first reports for Darien
      (Basilia anceps, Anatrichobius scorzai, Nycterophilia parnelli, T. johnsonae, T.
      parasiticus). All 74 bat fly species currently reported in Panama are presented
      in tabulated form. Of all screened bat flies, 30 bore Laboulbeniales fungi (7%).
      Based on both morphology and large ribosomal subunit (LSU) sequence data, we
      delimited 7 species of Laboulbeniales: Gloeandromyces nycteribiidarum (newly
      reported for Panama), G. pageanus, G. streblae, Nycteromyces streblidinus, and 3
      undescribed species. Of the 30 infected flies, 21 were Trichobius joblingi. This
      species was the only host on which we observed double infections of
      Laboulbeniales.

PMID- 29633708
TI  - Molecular and serological prevalence of Toxoplasma gondii and Anaplasma spp.
      infection in goats from Chongqing Municipality, China.
AB  - Toxoplasmosis and anaplasmosis are severe zoonotic diseases, the former caused by
      Toxoplasma gondii and the latter by Anaplasma spp. In the present study, 332 goat
      blood samples were randomly collected from Chongqing Municipality, China to
      screen for T. gondii and Anaplasma spp. We used a polymerase chain reaction (PCR)
      to detect DNA, and enzyme-linked immunosorbent assay (ELISA) to test for T.
      gondii antibodies. The prevalence of T. gondii and Anaplasma spp. was 38% and 35%
      respectively by PCR, and 42% for T. gondii antibodies by ELISA. The co-infection
      rate by T. gondii and Anaplasma was 13%, where the two predominant pathogens co
      infecting were Anaplasma phagocytophilum + A. bovis (10%), followed by T. gondii
      + A. phagocytophilum (9.64%). While co-infection by three pathogens varied
      ranging from 1.81% to 5.72%, less than 1% of goats were found to be positive for
      four pathogens. This is the first investigation of T. gondii and Anaplasma spp.
      infection in goats from Chongqing.

PMID- 29633709
TI  - Seroprevalence of Toxoplasma gondii in free-living European mouflon (Ovis
      orientalis musimon) hunted in central Germany.
AB  - Despite increasing consumption of mouflon (Ovis orientalis musimon) meat in
      Germany, there is currently no surveillance of Toxoplasma gondii infection in
      populations of these animals and generally little knowledge about the prevalence
      of this protozoan in German wild ungulates. Between 2011 and 2015, we collected
      138 blood samples from a free-living mouflon population in central German and
      tested sera for the presence of T. gondii antibodies using a modified
      agglutination test (MAT, cut-off 1:20). Antibodies were detected in 31 of the 138
      samples (22.46%). There was a significant difference in seroprevalence between
      the different age classes, with antibodies to T. gondii more frequent in adults.
      In contrast, there was no significant difference in seroprevalence depending on
      sex and year of sample collection. Game meat is frequently consumed as raw or
      undercooked meat and may therefore represent a potential source of human
      infection with T. gondii.

PMID- 29633710
TI  - Angiostrongylus costaricensis infection in Martinique, Lesser Antilles, from 2000
      to 2017.
AB  - Human abdominal angiostrongyliasis (HAA) is a parasitic disease caused by the
      accidental ingestion of the nematode Angiostrongylus costaricensis in its larval
      form. Human infection can lead to severe ischemic and inflammatory intestinal
      lesions, sometimes complicated by life-threatening ileal perforations. Only one
      case had been reported in Martinique, an Island in the French Antilles, in 1988.
      We retrospectively reviewed the medical charts of patients diagnosed with
      abdominal angiostrongyliasis at the University Hospital of Martinique between
      2000 and 2017. The objectives of this study were to evaluate the incidence and
      perform a descriptive analysis of the clinical, biological, radiological, and
      histopathological features of HAA in Martinique. Two confirmed cases and two
      probable cases were identified in patients aged from 1 to 21 years during the 18
      year period, with an estimated incidence of 0.2 cases per year (0.003
      case/year/100.000 inhabitants (IC95% = 0.00-0.05)). All patients presented with
      abdominal pain associated with high blood eosinophilia (median: 7.24 G/L [min
      4.25; max 52.28 G/L]). Two developed ileal perforation and were managed by
      surgery, with diagnostic confirmation based on histopathological findings on
      surgical specimens. The other two cases were probable, with serum specimens
      reactive to Angiostrongylus sp. antigen in the absence of surgery. All cases
      improved without sequelae. The description of this case series highlights the
      need to increase awareness of this life-threatening disease in the medical
      community and to facilitate access to specific diagnostic tools in Martinique.
      Environmental and epidemiological studies are needed to broaden our knowledge of
      the burden of this disease.

PMID- 29633712
TI  - Regaining the senses of touch and movement.
AB  - Artificially activating neurons in the cortex can make a tetraplegic patient feel
      naturalistic sensations of skin pressure and arm movement.

PMID- 29633713
TI  - Correction: PGAM5 promotes lasting FoxO activation after developmental
      mitochondrial stress and extends lifespan in Drosophila.

PMID- 29633711
TI  - Dynamic representation of 3D auditory space in the midbrain of the free-flying
      echolocating bat.
AB  - Essential to spatial orientation in the natural environment is a dynamic
      representation of direction and distance to objects. Despite the importance of 3D
      spatial localization to parse objects in the environment and to guide movement,
      most neurophysiological investigations of sensory mapping have been limited to
      studies of restrained subjects, tested with 2D, artificial stimuli. Here, we show
      for the first time that sensory neurons in the midbrain superior colliculus (SC)
      of the free-flying echolocating bat encode 3D egocentric space, and that the
      bat's inspection of objects in the physical environment sharpens tuning of single
      neurons, and shifts peak responses to represent closer distances. These findings
      emerged from wireless neural recordings in free-flying bats, in combination with
      an echo model that computes the animal's instantaneous stimulus space. Our
      research reveals dynamic 3D space coding in a freely moving mammal engaged in a
      real-world navigation task.

PMID- 29633715
TI  - Willingness for deceased organ donation under different legislative systems in
      Hong Kong: population-based cross-sectional survey.
AB  - INTRODUCTION: Under the current opt-in system, the deceased organ donation rate
      remains low in Hong Kong. An opt-out system and an opt-in system combined with
      organ allocation priority (ie, priority to donors as transplant recipients) have
      been proposed to encourage willingness among the general population towards
      deceased organ donation. This study aimed to compare willingness, and its
      determinants, across these three legislative systems. METHODS: A random telephone
      survey of Hong Kong permanent residents aged >=18 years was conducted between
      August and October 2016 using an anonymous questionnaire. Willingness towards
      deceased organ donation was compared between the legislative systems with
      McNemar's test. Determinants of willingness were tested by logistic regression.
      RESULTS: The proportion of those willing to consider deceased organ donation
      under the current opt-in system would significantly increase after combining it
      with allocation priority (64.5% vs 73.4%; P=0.018). "Fairness or reciprocity" was
      the major reported reason underlying the increase. In contrast, willingness would
      decrease after introducing the opt-out system (60.1%), although not significantly
      (P=0.336). The reduction might be attributable to a "belief of being forced to
      donate". Under the allocation priority system, reduced willingness to donate was
      associated with advanced age, lower educational attainment, and lower monthly
      household income. Under the opt-out system, reduced willingness was associated
      with being married, having a lower household income, and distrust of local
      government. CONCLUSIONS: An opt-in system with allocation priority could induce
      willingness to donate, whereas an opt-out system may reduce willingness. The
      findings have implications for policy-making and promotion of organ donation.

PMID- 29633716
TI  - Enhancing hydrogen storage performances of MgH2 by Ni nano-particles over
      mesoporous carbon CMK-3.
AB  - Nano-dispersed Ni particles over mesoporous carbon material CMK-3 (Ni/CMK-3) was
      fabricated by means of impregnation-reduction strategy using precursor NiCl2 .
      6H2O, which is beneficial to improving the de/rehydrogenation performances of
      MgH2. The dehydrogenation onset temperature of MgH2-Ni/CMK-3 is significantly
      lowered by 170 K from that of pristine MgH2 (around 603 K). Totally 5.9 wt% of
      hydrogen absorption capacity is liberated within 1 h at a temperature of 423 K
      under a pressure of 3 MPa. This composite can absorb 3.9 wt% hydrogen even at a
      temperature of 328 K under 3 MPa H2. Activation energy values of both
      dehydrogenation (43.4 kJ mol-1) and rehydrogenation (37.4 kJ mol-1) for MgH2
      Ni/CMK-3 are greatly enhanced from those of as-milled MgH2. Ni/CMK-3 also
      slightly destabilizes the dehydrogenation of MgH2 by 1.5 kJ mol [Formula: see
      text] The enhanced performances can be attributed to the synergistic effects of
      both destabilization and activation from nano-dispersed Ni particles.

PMID- 29633714
TI  - Proprioceptive and cutaneous sensations in humans elicited by intracortical
      microstimulation.
AB  - Pioneering work with nonhuman primates and recent human studies established
      intracortical microstimulation (ICMS) in primary somatosensory cortex (S1) as a
      method of inducing discriminable artificial sensation. However, these artificial
      sensations do not yet provide the breadth of cutaneous and proprioceptive
      percepts available through natural stimulation. In a tetraplegic human with two
      microelectrode arrays implanted in S1, we report replicable elicitations of
      sensations in both the cutaneous and proprioceptive modalities localized to the
      contralateral arm, dependent on both amplitude and frequency of stimulation.
      Furthermore, we found a subset of electrodes that exhibited multimodal
      properties, and that proprioceptive percepts on these electrodes were associated
      with higher amplitudes, irrespective of the frequency. These novel results
      demonstrate the ability to provide naturalistic percepts through ICMS that can
      more closely mimic the body's natural physiological capabilities. Furthermore,
      delivering both cutaneous and proprioceptive sensations through artificial
      somatosensory feedback could improve performance and embodiment in brain-machine
      interfaces.

PMID- 29633717
TI  - Thermoelectricity in correlated narrow-gap semiconductors.
AB  - We review many-body effects, their microscopic origin, as well as their impact on
      thermoelectricity in correlated narrow-gap semiconductors. Members of this class
      such as FeSi and FeSb2-display an unusual temperature dependence in various
      observables: insulating with large thermopowers at low temperatures, they turn
      bad metals at temperatures much smaller than the size of their gaps. This
      insulator-to-metal crossover is accompanied by spectral weight-transfers over
      large energies in the optical conductivity and by a gradual transition from
      activated to Curie-Weiss-like behaviour in the magnetic susceptibility. We show a
      retrospective of the understanding of these phenomena, discuss the relation to
      heavy-fermion Kondo insulators-such as Ce3Bi4Pt3 for which we present new results
      and propose a general classification of paramagnetic insulators. From the latter,
      FeSi emerges as an orbital-selective Kondo insulator. Focussing on intermetallics
      such as silicides, antimonides, skutterudites, and Heusler compounds we showcase
      successes and challenges for the realistic simulation of transport properties in
      the presence of electronic correlations. Further, we explore new avenues in which
      electronic correlations may contribute to the improvement of thermoelectric
      performance.

PMID- 29633718
TI  - Laser irradiation-induced laminated graphene/MoS2 composites with synergistically
      improved tribological properties.
AB  - Engineering lubricant additives that have extraordinary friction reduction and
      anti-wear performance is critical to almost any modern mechanical machines. Here,
      we demonstrate the fabrication of laminated lubricant additives that can combine
      the advantages of zero-dimensional nanospheres and two-dimensional nanosheets. A
      simple in situ laser irradiation method is developed to prepare the laminated
      composite structure composed of ideally ultrasmooth MoS2 sub-microspheres
      embedded within multiple layers of graphene. These ultrasmooth MoS2 spheres
      within the laminated structure can change sliding friction into rolling friction
      under strong shear force created by moving contact surfaces to significantly
      reduce the friction. Meantime, the graphene layers can behave as 'protection
      pads' to efficiently avoid the formation of scars on the metal-to-metal contact
      surfaces. Overall, the laminated composites as lubricant additives
      synergistically improve the friction reduction and anti-wear properties.
      Additionally, due to the unique loosely packed laminated structure, the
      composites can stably disperse in the lubricant for more than 15 d and work under
      high temperatures without being oxidized. Such constructed laminated composites
      with outstanding tribological properties by an in situ laser irradiation method
      supply a new concept in designing lubricant additives that can combine the
      advantages of 0D and 2D structures.

PMID- 29633719
TI  - Magnetic reversal and thermal stability of CoFeB perpendicular magnetic tunnel
      junction arrays patterned by block copolymer lithography.
AB  - Dense arrays of pillars, with diameters of 64 and 25 nm, were made from a
      perpendicular CoFeB magnetic tunnel junction thin film stack using block
      copolymer lithography. While the soft layer and hard layer in the 64 nm pillars
      reverse at different fields, the reversal of the two layers in the 25 nm pillars
      could not be distinguished, attributed to the strong interlayer magnetostatic
      coupling. First-order reversal curves were used to identify the steps that occur
      during switching, and the thermal stability and effective switching volume were
      determined from scan rate dependent hysteresis measurements.

PMID- 29633720
TI  - Use of active personal dosimeters in hospitals: EURADOS survey.
AB  - Considering that occupational exposure in medicine is a matter of growing
      concern, active personal dosimeters (APDs) are also increasingly being used in
      different fields of application of ionising radiation in medicine. An extensive
      survey to collect relevant information regarding the use of APDs in medical
      imaging applications of ionising radiation was organised by the EURADOS (European
      Radiation Dosimetry Group) Working Group 12. The objective was to collect data
      about the use of APDs and to identify the basic problems in the use of APDs in
      hospitals. APDs are most frequently used in interventional radiology and
      cardiology departments (54%), in nuclear medicine (29%), and in radiotherapy
      (12%). Most types of APDs use silicon diodes as the detector; however, in many
      cases their calibration is not given proper attention, as radiation beam
      qualities in which they are calibrated differ significantly from those in which
      they are actually used. The survey revealed problems related to the use of APDs,
      including their reliability in pulsed x-ray fields that are widely used in
      hospitals. Guidance from regulatory authorities and professional organisations on
      the testing and calibration of APDs used in hospital would likely improve the
      situation.

PMID- 29633721
TI  - Fractal form PEDOT/Au assemblies as thin-film neural interface materials.
AB  - Electrically conducting polymer formulations have emerged as promising approaches
      for the development of interfaces and scaffolds in neural engineering,
      facilitating the development of physicochemically modified constructs capable of
      cell stimulation through electrical and ionic charge transfer. In particular,
      topographically functionalized or neuromorphic materials are able to guide the
      growth of axons and promote enhanced interfacing with neuroelectrodes in vitro.
      In this study, we present a novel method for the formation of conducting
      polymer/gold assemblies via a combinational sputter and spin coating technique.
      The resulting multilayered PEDOT/Au substrates possessed enhanced electrochemical
      properties as a function of the number of deposited organic/inorganic layers. It
      was observed that through subsequent electrochemical conditioning it was possible
      to form neuromorphic fractal-like assemblies of gold particles, which
      significantly impacted on the electrochemical characteristics of the PEDOT/Au
      films. PEDOT/Au assemblies were observed to possess unique topographical
      features, advantageous charge storage capacity (34.9 +/- 2.6 mC cm-2) and low
      electrical impedance (30 +/- 2 Omega at 1 kHz). Furthermore, PEDOT/Au assemblies
      were observed to facilitate the outgrowth of neurites in a mixed ventral
      mesencephalon cell population and promotean increase in the neurons/astrocytes
      ratio relative to all experimental groups, indicating PEDOT/Au biomimetic
      neuromorphic assemblies as promising materials in engineering electrically
      conductive neural interface systems.

PMID- 29633722
TI  - A novel ratiometric fluorescent sensor for Ag+ based on two fluorophores.
AB  - A novel ratiometric fluorescent probe BCB was reported for the first time for the
      sensitive and selective analysis of Ag+ based on two Boradiazaindacene (BODIPY)
      as both the reference fluorophore and recognition part. Upon the addition of Ag+
      ions, a strong fluorescence emission at 570 nm from recognition BODIPY would be
      appeared, whereas the fluorescence of the other BODIPY at 535 nm would be a
      constant reference fluorescence signal. As a result, the ratio of fluorescence
      intensity (lambda570/lambda535) was changed from 0.16 to 1.0. And the selectivity
      of BCB towards Ag+ over other metal ion was excellent. Other metal ions, such as
      Cd2+, Cu2+, Fe3+, Hg2+, Mg2+, Ni2+, Pb2+ and Zn2+ showed negligible changes in
      the both absorption and fluorescence spectra of BCB.

PMID- 29633723
TI  - Synaptic characteristics with strong analog potentiation, depression, and short
      term to long-term memory transition in a Pt/CeO2/Pt crossbar array structure.
AB  - A crossbar array of Pt/CeO2/Pt memristors exhibited the synaptic characteristics
      such as analog, reversible, and strong resistance change with a ratio of ~103,
      corresponding to wide dynamic range of synaptic weight modulation as potentiation
      and depression with respect to the voltage polarity. In addition, it presented
      timing-dependent responses such as paired-pulse facilitation and the short-term
      to long-term memory transition by increasing amplitude, width, and repetition
      number of voltage pulse and reducing the interval time between pulses. The memory
      loss with a time was fitted with a stretched exponential relaxation model,
      revealing the relation of memory stability with the input stimuli strength. The
      resistance change was further enhanced but its stability got worse as increasing
      measurement temperature, indicating that the resistance was changed as a result
      of voltage- and temperature-dependent electrical charging and discharging to
      alter the energy barrier for charge transport. These detailed synaptic
      characteristics demonstrated the potential of crossbar array of Pt/CeO2/Pt
      memristors as artificial synapses in highly connected neuron-synapse network.

PMID- 29633724
TI  - Measurement of scattered and transmitted x-rays from intra-oral and panoramic
      dental x-ray equipment.
AB  - The aim of this study was to quantify the levels of transmitted radiation arising
      from the use of intra-oral dental x-ray equipment and scattered radiation arising
      from the use of both intra-oral and panoramic x-ray equipment. Levels of
      scattered radiation were measured at 1 m from a phantom, using an ion chamber
      with a volume of 1800 cm3. Transmitted radiation was measured using both (i) a
      phantom and dose-area product (DAP) meter and (ii) a patient and a 1800 cm3 ion
      chamber. For intra-oral radiography the patient study gave a maximum transmission
      of 1.80% (range 0.04-1.80%, mean 0.26%) and the phantom study gave a maximum
      transmission of 6% (range 2-6%, mean 5%). The maximum scattered radiation, per
      unit DAP, was 5.5 nGy (mGy cm2)-1 at 70 kVp and a distance of 1 m. For panoramic
      radiography the maximum scattered radiation was 9.3 nGy (mGy cm2)-1 at 80 kVp and
      a distance of 1 m. Dose values are presented to enable the calculation of
      adequate protective measures for dental radiography rooms. Previous studies have
      used a phantom and measured radiation doses at 1 m from the phantom to determine
      the radiation dose transmitted through a patient, whereas this study uses both
      patient and phantom measurements together with a large-area dosemeter, positioned
      to capture the entire x-ray beam, to ensure that more realistic dose measurements
      can be made.

PMID- 29633725
TI  - Surface plasmon resonance induced enhancement of photoluminescence and Raman line
      intensity in SnS quantum dot-Sn nanoparticle hybrid structure.
AB  - In this article, we report on enhancement in photoluminescence and Raman line
      intensity of SnS quantum dots embedded in a mesh of Sn nanostructures. SnS
      nanoparticles synthesized by homogenous precipitation method show strong quantum
      confinement with a band gap of ~2.7 eV (blue shift of ~1 eV compared to bulk SnS
      particles). The optical band gap of SnS quantum dots is controlled by varying the
      pH (~0 to 2.25), ageing time (24 to 144 h) and molarity (0 to 2 M) of the
      precursors. These SnS nanoparticles are embedded in a mesh of Sn nanostructures
      which are synthesized from tin chloride by using sodium borohydride as reducing
      agent. The Sn nanostructures have a morphology dependent, tunable surface plasmon
      resonance (SPR), ranging from UV (~295 nm) to visible region (~400 nm) of the
      electromagnetic spectrum. In the SnS-Sn nanohybrids, the excitons are strongly
      coupled with plasmons leading to a shift in the excitonic binding energy (~400
      meV). The pure SnS quantum dots have a very weak photoluminescence peak at ~560
      nm and Raman shift of low intensity at 853.08 cm-1, 1078.17 cm-1, 1255.60 cm-1,
      1466.91 cm-1. The coupling of SnS nanoparticles with Sn nanoparticles results in
      strong exciton-plasmon interactions leading to enhanced photoluminescence and
      Raman line intensity. The nanohybrids formed using Sn nanosheets whose SPR
      matches with absorption onset of the SnS nanoparticles shows an enhancement of
      ~104 times higher than pure SnS nanoparticles. Thus, Sn nanosheet with surface
      plasmon resonance in visible region (400 nm) like Au and Ag is a promising
      material for surface enhanced Raman spectroscopy, plasmon assisted fluorescence
      imaging and for enhancing the emission intensity of semiconductors with weak
      emission intensity.

PMID- 29633726
TI  - Haematological malignancies in Qatar: from childhood to adulthood.
AB  - Not available.

PMID- 29633727
TI  - Testicular damage in children and adolescents treated for malignancy: a short
      review.
AB  - Significant advances have been made over recent decades in the treatment of
      childhood malignancies. These advances had an incredible cost, as an increasing
      number of young survivors suffer subfertility or infertility, because of the high
      sensitivity of testicular cells, especially the rapidly dividing germ cells, to
      cytotoxic drugs and irradiation. Therefore, the impact of treatment on future
      fertility is of significant concern, both to parents and patients. Assessment of
      fertility damage in childhood remains problematic. For post-pubertal males, semen
      analysis represents a good indicator of spermatogenesis and testicular function,
      and allows for sperm cryopreservation. The available method for prepubertal
      children is only gonadal tissue cryopreservation. This method is still
      experimental and raises ethical concerns. Ideally, a multidisciplinary team
      approach needs to be used in addressing the needs of fertility preservation for
      this population. Precise knowledge of these issues would help pediatric
      oncologists and endocrinologists to counsel their patients and inform them for
      factors and resources that may protect or preserve parenthood options in the
      future.

PMID- 29633728
TI  - The Impact of Iron Overload in Patients with Acute Leukemia and Myelodysplastic
      Syndrome on Hepatic and Endocrine functions.
AB  - Patients with hematologic malignancies undergoing chemotherapy and requiring
      blood transfusion usually have an elevated serum ferritin. These findings have
      led to the suggestion that iron overload is common and may have deleterious
      effects in these patients. However, the relationship between serum ferritin and
      parenchymal iron overload in such patients is unknown. Therefore, we measured the
      liver iron content (LIC) by the FerriScan(r) method and investigated the liver
      function and some endocrine tests in 27 patients with acute leukemia (AL) or
      myelodysplastic syndromes (MDS). Using FerriScan(r) method, the normal mean LIC
      levels are: 4.3 +/- 2.9 mg Fe/g dry weight (d.w.). In our patients, the mean
      serum ferritin level was 1965 +/- 2428 ng/mL. In our patients, the mean total
      iron in the blood received by them was 7177 +/- 5009 mg. In 6 out of 27 patients
      LIC was > 7 mg Fe/g d.w. and in 11/27 serum ferritin was > 1000 ng/ml. Measuring
      fasting blood glucose revealed 3/27 with diabetes mellitus and 4/27 with impaired
      fasting glucose (IFG). All patients had normal serum concentrations of calcium,
      parathormone (PTH), free thyroxine (FT4) and thyrotropin (TSH). Four patients had
      elevated serum alanine transferase (ALT). LIC was correlated significantly with
      ferritin level (r = 0.5666; P < 0.001) and the cumulative amount of iron in the
      transfused blood (r = 0.523; P <0.001). LIC was correlated significantly with ALT
      (r = 0.277; P = 0.04) and fasting blood glucose (FBG) was correlated
      significantly with the amount of iron transfused (r = 0.52, p < 0.01) and ALT
      level (r = 0.44; P< 0.01). The age of patients did not correlate with LIC, FBG or
      ALT. In conclusions, these results contribute to our understanding of the
      prevalence of dysglycemia and hepatic dysfunction in relation to parenchymal iron
      overload in patients with hematologic malignancies undergoing chemotherapy and
      requiring blood transfusions.

PMID- 29633729
TI  - Hypercalcemia and acute pancreatitis in a male patient with acute promyelocytic
      leukemia and pulmonary tuberculosis.
AB  - We report a rare case of hypercalcemia and acute pancreatitis in a subject with
      acute promyelocytic leukemia (APL) and pulmonary tuberculosis, during all-trans
      retinoic acid (ATRA) treatment. Both associated complications were potentially
      due to several causes. A careful monitoring and exclusion of all causative
      factors must be addressed. Further research is necessary to improve our
      understanding of risk factors for these complications in patients with (APL).
      Studying these patterns may help us to improve outcomes for all children and
      young adults with hematologic malignancies.

PMID- 29633730
TI  - An uncommon case of chronic myeloid leukemia with variant cytogenetic.
AB  - Chronic Myeloid Leukemia (CML) is myeloproliferative neoplasm characterized by
      Philadelphia chromosome which is a balanced translocation between chromosome 9
      and 22 in 90% of cases. However, variant cytogenetic still happens in 5-10 % of
      cases, the importance of which is controversial as well as its response to
      therapy, prognosis and progression to acute leukemias. Here we report a male
      patient with CML and variant cytogenetic who responded to low dose of Dasatinib
      (50 mg daily).

PMID- 29633731
TI  - Thrombocytosis in a male patient with acute promyelocytic leukaemia during all
      trans retinoic (ATRA) acid treatment.
AB  - We present a rather uncommon side effect observed in a 20-year-old man with acute
      promyelocytic leukemia during treatment with ATRA. He developed a high platelet
      counts reaching up to 1655*109/L on day 29 of ATRA treatment, and started to
      recover spontaneously on day 33 of treatment, without any change in ATRA, or
      adding any cytoreduction therapy. No complications associated with thrombocytosis
      were observed. IL-6 seems to play an important role in the pathogenesis of the
      thrombocytosis induced by ATRA. However, it is unclear what are the precipitating
      factors for this rare phenomenon and whether it is caused by certain predisposing
      factors that might be related to patient's, disease pathogenesis or other unknown
      factors.

PMID- 29633732
TI  - Chronic Myeloid Leukemia with cryptic Philadelphia translocation and
      extramedullary B-lymphoid blast phase as an initial presentation.
AB  - Chronic Myeloid Leukemia (CML) is a clonal myeloproliferative neoplasm (MPN)
      characterized by the presence of a reciprocal translocation between the long arms
      of chromosomes 9 and 22, t(9;22)(q34:q11), resulting in fusion of the break point
      cluster region (BCR) with the ABL gene, which forms an oncogene, the transcript
      of which is an oncoprotein with a tyrosine kinase function. In the great majority
      of CML; BCR/ABL1 is cytogenetically visualized as t(9;22); giving rise to the Ph
      chromosome, harboring the chimeric gene. Cryptic or masked translocations occur
      in 2-10% patients with no evidence for the BCR/ABL rearrangement by conventional
      cytogenetics but are positive by Fluorescence in Situ Hybridization (FISH) and/or
      reverse transcriptase polymerase chain reaction (RT-PCR). These patients are
      described as Philadelphia negative (Ph negative) BCR/ABL1- positive CML with the
      chimeric gene present on the derivative chromosome 22, as in most CML cases, or
      alternatively on the derivative 9 in rare occasions. In the majority of cases,
      CML is diagnosed in the chronic phase; it is less frequently diagnosed in
      accelerated crises, and occasionally, its initial presentation is as acute
      leukemia. The prevalence of extramedullary blast phase (BP) has been reported to
      be 7-17% in patients with BP. Surprisingly, no extra-medullary blast crises of B-
      lymphoid lineage have been reported before among cases of CML as the initial
      presentation. We report an adult male diagnosed as CML- chronic phase when he was
      shortly presented with treatment-naive extramedullary B-lymphoid blast crises
      involving multiple lymph nodes, with no features of acceleration or blast crises
      in the peripheral blood (PB) and bone marrow (BM). In addition the patient had
      variant/cryptic Philadelphia translocation. This is the first report of CML, on
      the best of our knowledge, with extramedullary B-lymphoid blast phase, as initial
      presentation, that showed a cryptic Ph translocation.

PMID- 29633733
TI  - Diabetic ketoacidosis as the onset of type 1 diabetes in children.
AB  - Not available.

PMID- 29633734
TI  - Current treatment of hypoparathyroidism: Theory versus reality waiting guidelines
      for children and adolescents.
AB  - The diagnosis of hypoparathyroidism(HPT)is readily made in the presence of
      hypocalcemia with markedly reduced or absent parathormone (PTH) levels. Currently
      available treatments for HPT include high dose vitamin D (ergocalciferol, D2 and
      cholecalciferol, D3) or, the active metabolite dihydroxy vitamin D (calcitriol),
      in addition to calcium supplements.This regimen, if not well monitored, can lead
      to hypercalciuria, as PTH deficiency impairs renal calcium reabsorption. Thus the
      goal of treatment, is to maintain serum calcium at the low end of the normal
      range. Undertreatment can cause symptomatic hypocalcemia, while overtreatment
      hypercalciuria, which may lead to nephrolithiasis, nephrocalcinosis, and renal
      insufficiency. At present, there is no consensus on the management of HPT in
      children and adolescents and only few studies are available on the long term
      outcome of patients with recombinant HPT treatment. The purpose of this article
      is to review, in a comprehensive manner, the major aspects of HPT management in
      children and adolescents waiting for authoritative guidelines for the treatment
      of HPT in this group of patients. Further research, addressing specific questions
      for this population are urgently needed to improve long-term safety of patients.
      Educational interventions are also needed for professionals, parents and patients
      to enable them to improve knowledge, quality of life and effective management
      care at home.

PMID- 29633735
TI  - Endocrinopathies in celiac disease: When the endocrinologist sees what is
      invisible to the gastroenterologist.
AB  - Celiac disease (CD) is a systemic, immune mediated and genetically determined
      small intestinal disorder characterized by intolerance to dietary gluten that
      generally presents with gastrointestinal symptoms in young children and extra
      intestinal manifestations. Furthermore, there is close association between CD and
      endocrine diseases, including diabetes, autoimmune thyroid diseases, growth and
      pubertal disorders, etc. probably due to the presence of a common genetic
      predisposition. The present review aims to highlight and give more insight to the
      endocrine changes in CD, especially when there are few or no gastrointestinal
      symptoms and to emphasize on screening opportunities in some endocrine diseases.

PMID- 29633736
TI  - Thyroid Disorders in Subjects with Down Syndrome: An Update.
AB  - Down syndrome (DS) is the commonest chromosomal disorder among live born infants.
      DS is associated with increased risk of endocrine abnormalities particularly
      thyroid gland disorders. The spectrum of thyroid dysfunction in patients with DS
      include congenital hypothyroidism, subclinical hypothyroidism, acquired
      hypothyroidism (autoimmune - non autoimmune), and hyperthyroidism. This review
      will focus on the characteristics of the different presentations of thyroid
      abnormalities in DS, screening and management recommendations.

PMID- 29633737
TI  - Smartphone APPlications in the clinical care and management of Rheumatic
      Diseases.
AB  - BACKGROUND: Rheumatic diseases (RDs) are the most common cause of severe long
      term pain and physical disability, affecting hundreds of millions of people
      around the world. Smartphones technology have the potential to become an
      important tool that rheumatologist can employ in the clinical care management of
      RD. METHODS: Research of the published literature on the principle electronic
      databases available as Ovid MEDLINE, Health Technology Assessment Database,
      Embase, and PsycINFO was conducted, and the studies evaluated eligible were
      reviewed. RESULTS: Our search produced 120 results from which 47 eligible
      articles were identified reporting studies of smartphone apps for patients with
      RD. All examined feasibility and five assessed the efficacy of a smartphone
      intervention for clinical care management. CONCLUSIONS: It has been demonstrated
      a strong evidence for the feasibility of using smartphone to enhance care of
      patients with RD.  Based on the available literature and our personal
      experiences, we consider useful the development of some mobile phone apps, to
      simplify and assist the rheumatologist during his clinical practice. Still
      remains limited data on the efficacy of such interventions.

PMID- 29633738
TI  - The ethics of organizational change in healthcare.
AB  - The article addresses the increasingly important issue of organizational ethics
      in healthcare. Assuming that the governance of organizational change consists of
      a seriousness of continuous choices and of objectives to be determined and
      achieved, a possible definition of this new discipline is then deepened, and its
      fields of application are identified. In the discussion therefore emerge the
      close link between ethical choice in organization and legality, passing through
      transparency and prevention of corruptive phenomena. After a focus on the
      strategic role played by the Medical Doctor of the healthcare management team, in
      conclusion, the need arises to support a strengthened supervisory and evaluation
      system and a culture of the ethical organizational choice of health managers, a
      rooting of the sense of identity and belonging to the healthcare organization and
      its mission by Professionals. Also governing this last aspect is the new
      challenge for the management of public healthcare enterprises.

PMID- 29633739
TI  - Aspirin for thromboprophylaxis in major orthopedic surgery: old drug, new tricks?
AB  - Major orthopedic surgery, mainly entailing hip fracture surgery, hip and knee
      arthroplasty, is associated with significant morbidity and mortality, which are
      especially attributable to the high risk of postoperative VTE. Such a
      considerable risk is mainly due to a procoagulant state sustained by several
      important mechanisms, including massive release of procoagulants from tissue and
      bone damage, blood vessel injury, reduced venous emptying, perioperative
      immobilization and cement polymerization, among others. The risk of VTE during
      and after major orthopedic surgery approximates 50-80% in patients with no
      thromboprophylaxis, and persists for up 3 to 6 months after surgery. The
      anticoagulant or antithrombotic armamentarium entails several anticoagulants such
      as heparin, coumarins, fondaparinux, and the recently developed DOACs inhibiting
      either activated factor Xa (i.e., rivaroxaban, apixaban, edoxaban) or thrombin
      (i.e., dabigatran), as well as aspirin, i.e., the oldest antiplatelet drug to be
      ever discovered and used in clinical practice. The current guidelines are not in
      complete agreement regarding the choice of the ideal thromboprophylaxis, since
      some consider aspirin, and some discourage it. Recent evidence seems to support
      the use of aspirin in selected situations and in selected protocols. Therefore,
      we believe that consideration should be made about increasing the use of this old
      but still effective drug for perioperative prophylaxis of VTE, especially in
      patients for whom the administration of DOACs may be challenging.

PMID- 29633740
TI  - Self-determination, healthcare treatment and minors in Italian clinical practice:
      ethical, psychological, juridical and medical-legal profiles.
AB  - BACKGROUND AND AIM: The social role of the minor, as indeed that of the
      physician, has changed markedly. This transformation has given rise to new
      patterns and responsibilities in the management of healthcare procedures that
      involve minors. DISCUSSION: According to international legislation, in the
      clinical setting, as in other areas of social life, minors have the right to be
      heard and to have their opinions taken into consideration as an increasingly
      determining factor, in accordance with their age and degree of maturity and
      discernment. The authors describe the right to information and the decision
      making process when the patient is a minor and underline the role of the parties
      involved (physicians, parents, under-age patient, judge) in various
      circumstances. Specifically, the paper analyzes the ethical and legal issues
      relating to the entitlement to  decisions concerning the medical treatment of
      children and assesses the importance that Italian law attaches to the will of
      minors in the healthcare choices that affect them. CONCLUSIONS: Healthcare
      workers  are called upon to face new challenges in order to ensure that
      healthcare services are able to safeguard the interests of minors while, at the
      same time, respecting their will. How to evaluate children's competence to
      consent and how to balance the autonomy of parents and minors are crucial
      questions which the law courts in the various countries are increasingly being
      asked to address. These issues require close collaboration among various figures
      (parents, doctors, psychologists, judges) and imply the ethical need to undergo
      continuous training.

PMID- 29633741
TI  - Intramuscular oxygen-ozone therapy in the treatment of low back pain.
AB  - BACKGROUND AND AIM OF THE WORK: Intramuscular paravertebral injections of ozone
      are minimally invasive, safe and efficacy in reducing pain and disability. The
      aim of this paper is to present the early results of paravertebral lumbar ozone
      injections in the treatment of low back pain. METHODS: Between February 2011 and
      December 2015, a total of 109 patients underwent intramuscular paravertebral
      lumbar injections of ozone due to low back pain. Of them, 42 interrupted the
      treatment at a medium of 5.4 injections and were lost to follow-up. Of the 67
      remaining patients, only 24 answered to our questionnaire. Local and radiating
      pain was assessed using a 10-cm horizontal Visual Analogue Scale. Perceived
      functional status and disability were evaluated using the Oswestry Disability
      Index, administered before treatment and one month after the last injection.
      RESULTS: Visual Analogue Scale reduction was demonstrated in 23 out of 29 cycles
      (79%) of ozone therapy. Regarding disability evaluation, Oswestry Disability
      Index score reduction was assessed in all except one. No complications were
      recorded. Our results are similar to the other reports: 79% of patients had VAS
      reduction of 2.3 points and all except one patient reported ODI reduction
      (average reduction of 9%). CONCLUSIONS: Lumbar paravertebral oxygen-ozone
      injections are minimally invasive, safe, cheaper and effective in relieving pain
      as well as disability. This technique is easy to perform, it doesn't need
      computed-tomography or anesthesiologist support. We suggest its application in
      low back pain as first choice to replace intradiscal computed-tomography-guided
      infiltrations and to avoid or delay surgery.

PMID- 29633742
TI  - A pilot study on sperm DNA damage in beta-thalassemia major: is there a role for
      antioxidants?
AB  - Excess iron deposition in patients with beta thalassemia major (BTM) causes
      excess free radical formation, damages the hypothalamic pituitary testicular axis
      and production of sperms with DNA defects. As antioxidants were reported to
      improve fertility in healthy males; their effectiveness to improve sperm DNA
      defects in adult males with BTM was studied. Twenty fully pubertal BTM patients
      were included consecutively, all had semen analysis; 10 were found to be
      azoospermic, so further analysis for sperms and DNA defects was conducted on the
      remaining 10 participants. Semen was analyzed for antioxidants in seminal plasma
      and sperms for defects including the DNA fragmentation index, sperm deformity
      index, teratozospermia index and acrosomal index. Participants were then given L
      carnitine and N-acetylcysteine for 6 months. All semen parameters were reassessed
      after treatment. The sperm deformity index and teratozospermia index increased
      significantly after treatment from 1.90+/-0.33 to 2.46+/-0.61 and from 1.59+/
      0.22 to 1.86+/-0.28 respectively. So, apparently antioxidants accentuated sperm
      deformities in men with BTM. Therefore, the results of this study are not in
      favour with the use of antioxidants in BTM patients for improving potential
      fertility. Larger studies, however, are needed to confirm these preliminary
      results.

PMID- 29633743
TI  - The frequency of hypothyroidism and its relationship with HCV positivity in
      patients with thalassemia major in southern Iran.
AB  - INTRODUCTION: Hypothyroidism is one the most complication due to iron overload in
      patients with beta-thalassemia major (TM). On the other hand these patients are
      prone to Hepatitis C virus (HCV) infection that can cause  thyroid dysfunction by
      itself or as the side effect of treatment with interferon (INF) or IFN plus
      ribavirin. The aim of this study is to evaluate the association of hypothyroidism
      with HCV positivity and serum ferritin levels in patients with TM. METHODS: In
      this cross-sectional study, 201 randomly selected patients with TM who were
      registered at the Thalassemia Clinic of a tertiary hospital in Shiraz, southern
      Iran were investigated. Thyroid function tests and serologic screening assays for
      HCV seropositivity (HCV Ab and HCV-RNA) were conducted for all patients. RESULTS:
      Frequency of hypothyroidism was 22.9% including 19.9% subclinical hypothyroidism,
      2% primary overt hypothyroidism and 1% central hypothyroidism. Eighty six
      patients (42.8%) were HCV Ab positive and 60 patients (29.9%) were HCV RNA
      positive. No significant relationship was found between hypothyroidism and HCV
      positivity or receiving IFN-alpha (P>0.05). Hypothyroidism showed a borderline
      significant association with high serum ferritin levels in TM patients (P=0.055).
      CONCLUSION: Our results showed no significant association between hypothyroidism
      and HCV infection in TM patients. It seems that the main mechanism of
      hypothyroidism in our patients is iron overload; however, for better evaluation a
      larger multicenter study is recommended.  Also due to the importance of
      consequences of HCV infection, more careful pre-transfusional screening of blood
      should be considered in TM patients.

PMID- 29633744
TI  - One-year experience in carotid endarterectomy combining general anaesthesia with
      preserved consciousness and sequential carotid cross-clamping.
AB  - BACKGROUND AND AIM OF THE WORK: We report 1-year single-centre experience in
      carotid endarterectomy (CEA) combining general anaesthesia with preserved
      consciousness (GAPC) and standardized carotid sequential cross-clamping, for our
      protocol effectiveness evaluation in reduction of perioperative stroke, death or
      cardiologic complications. METHODS: We considered all patients who underwent CEA
      in 2016. All patients underwent superficial cervical plexus block and GAPC with
      Remifentanil. The surgical technique consisted of common carotid artery (CCA)
      cross-clamping, carotid bifurcation isolation, external (ECA) and internal
      carotid artery (ICA) cross-clamping. After CCA cross-clamping, we performed a
      neurological tolerance test (NTT); this allowed selective shunting only for
      positive NTT. Primary end-points were: transient ischemic attack (TIA)/stroke,
      myocardial infarction, death in perioperative period. Secondary end-points were:
      carotid shunting, peripheral cranial nerves injuries (PCNI), GAPC intolerance,
      other complications, reintervention in perioperative period, length of hospital
      stay. RESULTS: 104 consecutive patients underwent CEA with this protocol in the
      considered period. Twenty-seven (25.9%) patients were symptomatic. Mean clamping
      time was 48+/-13.5 minutes. Five cases (4.8%) requested internal carotid artery
      shunting. No TIA/stroke, myocardial infarction or death were recorded in the
      perioperative period. PCNI were observed in 19 cases (18.2%) in the immediate
      post-operative period; 16 of them (84.2%) showed complete or partial resolution
      at discharge. Only one patient (0.9%) showed GAPC intolerance. No other
      complication occurred. Three patients (2.9%) underwent reintervention for neck
      haematoma drainage. Mean hospital stay were 3+/-0.9 days. CONCLUSIONS: GAPC
      associated with sequential carotid cross-clamping appeared to be safe and
      effective in prevention of major neurological and cardiologic complications
      during CEA.

PMID- 29633745
TI  - Diabetic ketoacidosis at the onset of Type 1 diabetes in young children Is it
      time to launch a tailored campaign for DKA prevention in children <5 years?
AB  - AIM: To analyze clinical characteristics associated with the occurrence of
      diabetic ketoacidosis (DKA) at the onset of type 1 diabetes (T1D) in children
      aged <5 years in order to identify early signs or symptoms useful to prevent DKA
      appearance. METHODS: Data of patients  with newly diagnosed TID aged <5 years
      (Group 1) and 6-10 years old  (Group 2) coming from the province of Parma were
      collected in the period 2012-2016. RESULTS: Mild/moderate ketoacidosis at
      diabetes diagnosis occurred more frequently in Group 1 than in Group 2 patients
      (p<0.0015). Severe DKA incidence was higher in children below 5 (21.8%) than in
      those over 5 years of age (3.75%; p=0.021). Latent period before overt T1D
      diagnosis was longer in Group 1 than in Group 2 patients (p=0.0081). During this
      latent period similar indicators were recorded among parents of children <3 years
      old: frequent use of disposable baby diapers (87%), wet baby diapers because of a
      large amount of urine (86%), body weight loss (79%).  In children aged 3-4 years
      reported symptoms consisted of polyuria (89%), polydipsia (79%), fatigue (72%).
      In Group 2 patients predominant signs concern unusual episodes of  enuresis.
      CONCLUSIONS: We believe that it is time to launch a DKA prevention campaign
      tailored for children under 5 years old and focused just on the above-mentioned
      three warning signs. Information program must involves pediatricians, pediatric
      nurses, new moms and nursery school teachers.

PMID- 29633746
TI  - Comparison between self-gripping, semi re-absorbable meshes with polyethylene
      meshes in Lichtenstein, tension-free hernia repair: preliminary results from a
      single center.
AB  - Even tough inguinal hernia repair is among the commonest operations in general
      surgery, the choice for an optimal approach continues to be a controversial
      topic. Because of the low recurrence rates and low prevalence of complications,
      tension-free mesh augmented operation has become the standard technique in
      inguinal hernia surgery, significantly reducing hernia recurrence rates. On the
      contrary, prevalence of chronic postoperative groin pain (CPGI) i.e. pain beyond
      a three month-postoperative period still remains significant: as rates of CPGI
      may range between 15% and 53%, surgical approaches aimed to avoid chronic post
      hernioplasty pain have been extensively debated, and the avoidance of CPGI has
      become one of the primary endpoints of surgical research on inguinal hernia
      repair). Recently, a sound base of evidence suggested that the entrapment of
      peripheral nervous fibers innervating part of the structures in the inguinal
      canal and stemming from ilioinguinal (Th12), iliohypogastric (L1) nerves as well
      as from the genital branch of the genito-femoral nerve (L1, L2), may eventually
      elicit CPGI (1-10). Consequently, innovative fixation modalities (e.g. self
      gripping meshes, glue fixation, absorbable sutures), and new material types (e.g.
      large-pored meshes) with self-adhesive sticking or mechanical characteristics,
      have been developed in order to avoid penetrating fixings such as sutures, clips
      and tacks. However, some uncertainties still remain about the pros and cons of
      such meshes in terms of chronic pain, as new, innovative mesh apparently does not
      significantly reduce the rate of CPGI. Parietex ProGrip(r) (MedtronicsTM) is a
      bicomponent mesh comprising of monofilament polyester and a semi re-absorbable
      polylactic acid gripping system that allows sutureless fixation of prosthetic
      mesh to the posterior inguinal wall. As ProGrip(r) does not requires additional
      fixation, inguinal canal may be closed within minutes after adequate groin
      dissection, ultimately shortening operating time. In other words, ProGrip(r) has
      the potential for significant savings, in terms of surgical and post-operating
      costs as well (10). The aim of our study is therefore to compare the results of
      the same technique with two different mesh materials (ProGrip(r) mesh vs.
      polyethylene mesh), in terms of operative time, post-operative pain,
      complications, and recurrence rates.

PMID- 29633747
TI  - Multidimensional approach usefulness in early Alzheimer's disease: Advances in
      clinical practice.
AB  - BACKGROUND AND AIM: Improving quality of life of patients with early Alzheimer's
      Disease (AD) is a primary concern of health professionals involved in dementia
      treatment. The aim of this study is to reveal associations among psychiatric
      symptoms and wellbeing aspects, dysfunctional lifestyles and stress-related
      behaviors, illness perception, personality traits, and life quality satisfaction,
      in order to offer a comprehensive evaluation of psychological and behavioral
      aspects characterizing patients with early AD. METHODS: This is a cross-sectional
      study in which all the outpatients included were evaluated at the Dementia Clinic
      in Parma (Italy). 21 patients with probable AD were assessed by an overall
      cognitive screening (Milan Overall Dementia Assessment), the evaluation of
      personal and instrumental autonomy (Activities of Daily Living and Instrumental
      Activities of Daily Living), and of dementia severity (Clinical Dementia Rating
      Scale). After the neurocognitive assessment, a wide battery of clinical and
      psychological measures (Symptom Questionnaire, Pisa Stress Questionnaire, Illness
      Behavior Questionnaire, Sixteen Personality Factor Questionnaire and Satisfaction
      Profile) was administered to the patients. Spearman's rho correlations between
      clinical and psychological measures were performed. RESULTS: A tendency to deny
      anxiety, depressive and somatic symptoms might be present in patients with early
      AD. They also present with hypochondriasis, resulting in higher level of anxiety
      and depression. Reduced liveliness and self-reliance as personality traits may
      influence the intensity of such symptoms. CONCLUSIONS: A comprehensive assessment
      including psychological and clinical measures should be routinely integrated in
      clinical practice for the evaluation of patients with early AD.

PMID- 29633748
TI  - The economic crisis and lifestyle changes: a survey on frequency of use of
      medications and of preventive and specialistic medical care, in the Marche Region
      (Italy).
AB  - BACKGROUND AND AIM: In the words of one observer, one of the many effects of the
      economic downturn has been a "health system shock" marked by reductions in the
      availability of healthcare resources and increases in the demand for health
      services. The financial situation influences negatively the low-income family
      groups, particularly those who normally use the government provided primary
      prevention services. The goal of this study was to assess the impact of the
      global recession on the use of medicines and medical investigation recession in
      different areas of the Marche Region. METHODS: An anonymous questionnaire
      prepared by the National Institute of Statistics, modified and validated by the
      University of Camerino, has been distributed to junior highschool students of
      Central Italy to provide a statistically representative sample of families. The
      questionnaire has been administered in 2016-2017. RESULTS: This article examines
      the results about healthcare habits, specifically, regarding medicines and
      medical examinations. Data obtained emphasize a reduction in the use of
      nonsteroidal anti-inflammatory drugs (NSAIDs). The parents category showed the
      higher change in medicines use (72.9%). Comparing the data of the Fabriano area
      with that of the Civitanova Marche area, Fabriano reported a greater reduction in
      the frequency of taking medicine. Concerning the medical examinations, half of
      the respondents (62.5%), indicated that they and their family members have
      regular medical check-up. CONCLUSIONS: Respondents who admitted that the economic
      crisis had reduced their quality of life indicated that the parents were the ones
      who had experienced the greatest change. This is confirmed by the information on
      the reduced frequency of medicine use, which affected the parents more than the
      children, whom they sought to protect and safeguard the most. This reduction was
      most marked in the Fabriano area. In contrast, in the Civitanova Marche area,
      with different socioeconomic characteristics, an increase in the use of all the
      categories of medicines was reported. Concerning visits the situation in the
      Marche Region appears encouraging.

PMID- 29633749
TI  - Survey about the potential effects of economic downturn on alcohol consumption,
      smoking and quality of life in a sample of Central Italy population.
AB  - BACKGROUND AND AIM OF THE WORK: Negative health effects have been associated with
      the changes in lifestyles in relation with the low income of population.
      Consequently, in our study we investigated the frequency changes of alcohol and
      smoke consumption, physical activity, and quality of life in families of Marche
      Region in Central Italy. METHODS: In the period 2016-2017, an anonymous
      questionnaire has been distributed to junior highschool students of Camerino,
      Fabriano, and Civitanova Marche of Marche Region. The Manchester Short Assessment
      of Quality of Life (MANSA), was used to assess subjective quality of life.
      RESULTS: Data obtained in this research were used to analyze lifestyle changes,
      specifically those involving alcohol consumption, smoking, and physical activity,
      and to assess perceived general quality of life. In all categories of population,
      an increase of frequency in alcohol consumption was observed. On the contrary,
      for the tobacco smoke we observed a reduction in particular in the parents
      category. The MANSA mean value was 4.5 with a Standard Deviation of 1.3.
      CONCLUSIONS: As underlighted, also, by results of the MANSA test we can
      hypothesize a reduction in the family income produces a change of lifestyles.

PMID- 29633750
TI  - Vascular Parkinsonism sensitive to Rotigotine therapy is found in aged patients:
      a clinical case description.
AB  - Previous and recent papers have pointed out several discussions about the so
      called 'Vascular Parkinsonism' (VP), particularly about some distinctive
      characteristics with respect to the Idiopathic Parkinson Disease (IPD);
      differences commonly described are  sudden onset of extrapyramidal symptoms after
      a stroke, main involvement of lower limbs in diffuse brain microinfarcts (lower
      body parkinsonism), low, short in time or absent response to classic IPD therapy
      in all kinds of vascular brain pathologies. But few published studies have also
      emphasized some relationship linking brain morphological signs of vascular damage
      in elder patients suffering from diagnosed IPD, both 'normally' responding to
      classic Levodopa therapy or not.

PMID- 29633751
TI  - Role of Transesophageal 3D Echocardiography in Adult Cor Triatriatum Diagnosis.
AB  - Cor triatriatum is a very rare congenital abnormality, symptomatic during
      childhood;the non restrictive form is usually diagnosed as an incidental finding.
      We report the case of a 88 years old man referred to our hospital for elective
      endovascular repair of an aortic aneurysm; transthoracic cardiac bidimensional
      echocardiography showed an abnormal mass into the left atrium and a the diagnosis
      of cor triatriatum was fully made by a three dimensional transesophageal
      echocardiography. 3D echocardiography is an excellent noninvasive method that
      provides a rapid bedside diagnosis , without having to use ionizing radiation.

PMID- 29633752
TI  - Hypochlorite accident during wndodontic therapy with nerve damage - A case
      report.
AB  - Endodontic therapy is a routinely practised clinical procedure with few reported
      complications but, as a bleaching agent, inadvertent spillage of sodium
      hypochlorite beyond the root canal system may result in extensive soft tissue or
      nerve damage, and even airway compromise. Although very rare, complications
      arising from hypochlorite extrusion beyond the root apex are described. NaOCl
      causes oxidation of protein and lipid membrane and causes necrosis, hemolysis and
      dermal ulcerations (2-4). Neurological complication are very rare. Paraesthesia
      and anaesthesia may affect the mental, inferior dental and infra-orbital branches
      of the trigeminal nerve and normal sensation may take many months to  completely
      resolve (6, 7). Nerve damage (the buccal branch) was described in 2005 by Witton
      et al. (8) and patients exhibited a loss of the naso-labial groove and a down
      turning of the angle of the mouth and the motor function was regained after
      several months. We present a case in which the extrusion of NaOCl solution during
      endodontic therapy led to important destructive effects on soft tissues and
      nerves. The arisen medico legal issues are discussed.

PMID- 29633753
TI  - Percutaneous treatment of traumatic talus extrusion: a case report.
AB  - BACKGROUND AND AIM OF WORK: Total traumatic extrusion of talus with interruption
      of all ligaments (missing talus) is a very rare injury. We represent the case of
      a 44-years-old male who reported total extrusion of talus and Lisfranc
      dislocation after a motorbike accident. This rare injury has a wide choice of
      treatment but usually there is not a successful functional restore. METHODS: We
      decided to treat the patient with an immediate reimplantation of extruded talus
      using 3 Kirschner wires and antibiotic therapy. We performed a temporary fixation
      of talus with calcaneus, tibia and scaphoid. RESULTS: Usually, this kind of
      injuries are treated with a tibiocalcaneal arthrodesis and show common
      complications such as avascular necrosis and infection. Against our expectations
      we managed to treat successfully our patient. CONCLUSIONS: After 5 years of
      follow up the patient reported good clinical outcomes without performing
      arthrodesis and recording major complications.

PMID- 29633754
TI  - A rare case of gint lipomatous hypertrophy of the atrial septum.
AB  - Benign lipomatous lesion of the heart includes  an heterogeneous group of
      entities including neoplastic, congenital and reparative phenomena. Among these
      lipomas and lipomatous hypertrophy of the atrial septum ( LHIS) represent the
      most common lesion. Patients suffering from LHIS are often asymptomatic, however
      atrial fibrillation, congestive heart failure and supraventricular tachycardia
      are typical findings. Here we present a rare case of LHIS symptomatic  for
      asthenia and dyspnea.

PMID- 29633755
TI  - Interleukin (IL)-13, Prostaglandin E2 (PGE2), and Prostacyclin 2 (PGI2) Activate
      Hepatic Stellate Cells via Protein kinase C (PKC) Pathway in Hepatic Fibrosis.
AB  - BACKGROUND Protein kinase C (PKC), interleukin (IL)-13, prostaglandin E2 (PGE2),
      and prostacyclin 2 (PGI2) can all play crucial roles in pulmonary fibrosis.
      However, their functions remain unclear in hepatic fibrosis mediated by hepatic
      stellate cells (HSCs), which has been demonstrated to be related to transforming
      growth factor-beta (TGF-beta) and platelet-derived growth factor (PDGF). MATERIAL
      AND METHODS All the experiments were based on LX-2 Hepatic stellate cells. The
      expression of TGF-beta1 and PDGF were assessed by ELISA, RT-PCR, and Western
      blotting in human HSCs treated by IL-13, PGE2, and PGI2, respectively. At the
      same time, bridge assay and CCK8 assay were used to detect the cell proliferation
      and activity, PKC activity assay was used to test the activity of PKC, and PKC
      agonist and antagonist were used to verify the results obtained previously.
      RESULTS We found that IL-13, PGE2, and PGI2 significantly enhanced the expression
      of TGF-beta1 and PDGF in human HSCs, which also clearly improved the
      proliferation and cell activity of HSCs. Moreover, PKC activity was significantly
      increased following IL-13, PGE2, and PGI2 treatments. We also found that the
      expression of TGF-beta1 and PDGF, as well as the proliferation and cell activity
      of HSCs, were significantly enhanced by the PKC agonist phorbol 12-myristate 13
      acetate (PMA), but suppressed by the PKC antagonist calphostin C. CONCLUSIONS We
      found that IL-13, PGE2, and PGI2 stimulated HSCs proliferation and secretion of
      TGF-beta1 and PDGF by activating PKC, which predicted their potential roles in
      hepatic fibrosis.

PMID- 29633756
TI  - Publisher Correction: Experimental orthotopic transplantation of a tissue
      engineered oesophagus in rats.
AB  - This corrects the article DOI: 10.1038/ncomms4562.

PMID- 29633757
TI  - Publisher Correction: Immediate tool incorporation processes determine human
      motor planning with tools.
AB  - This corrects the article DOI: 10.1038/ncomms5524.

PMID- 29633758
TI  - Publisher Correction: ZNF143 provides sequence specificity to secure chromatin
      interactions at gene promoters.
AB  - This corrects the article DOI: 10.1038/ncomms7186.

PMID- 29633759
TI  - Publisher Correction: miR-196b directly targets both HOXA9/MEIS1 oncogenes and
      FAS tumour suppressor in MLL-rearranged leukaemia.
AB  - This corrects the article DOI: 10.1038/ncomms1681.

PMID- 29633760
TI  - Publisher Correction: Species traits and phylogenetic conservatism of climate
      induced range shifts in stream fishes.
AB  - This corrects the article DOI: 10.1038/ncomms6053.

PMID- 29633762
TI  - Publisher Correction: In vivo single-molecule imaging of syntaxin1A reveals
      polyphosphoinositide- and activity-dependent trapping in presynaptic
      nanoclusters.
AB  - This corrects the article DOI: 10.1038/ncomms13660.

PMID- 29633763
TI  - Author Correction: The transcriptional repressor complex FRS7-FRS12 regulates
      flowering time and growth in Arabidopsis.
AB  - This corrects the article DOI: 10.1038/ncomms15235.

PMID- 29633764
TI  - Publisher Correction: General rules for the arrangements and gating motions of
      pore-lining helices in homomeric ion channels.
AB  - This corrects the article DOI: 10.1038/ncomms5641.

PMID- 29633765
TI  - Hybrid MoSe2-indocyanine green nanosheets as a highly efficient phototheranostic
      agent for photoacoustic imaging guided photothermal cancer therapy.
AB  - Phototheranostic technology based on photoacoustic imaging (PAI) and photothermal
      therapy (PTT) is emerging as a powerful tool for tumor theranostic applications.
      For effective tumor eradication, a novel PAI/PTT theranostic nanoagent with an
      excellent optical absorption and photothermal capability is highly desired.
      Herein, we present a new PAI/PTT nanohybrid named sMoSe2-ICG NSs by covalently
      conjugating aminated indocyanine green (ICG) onto a single layer of molybdenum
      selenide nanosheets (sMoSe2 NSs). We first validate the sMoSe2-ICG NS agent for
      the PAI and PTT effect in vitro and then use it for highly-sensitive PAI guided
      highly efficient tumor PTT in vivo. The sMoSe2-ICG NS hybrid possesses several
      advantages for PAI/PTT applications: (1) the sMoSe2-ICG NSs have strong
      absorbance in the broad near-infrared (NIR) region, enabling a highly efficient
      PAI/PTT theranostic effect and the selection of the most widely used excitation
      wavelength of 808 nm for PTT; (2) the photothermal ability of ICG in sMoSe2-ICG
      NSs is augmented due to ICG aggregation induced fluorescence quenching and the re
      absorbance of ICG fluorescence by sMoSe2 NSs, which further enhances the PAI/PTT
      theranostic effect. (3) The characteristic absorption peak of sMoSe2-ICG NSs is
      red-shifted compared to free ICG, resulting in a higher PAI signal-to-noise ratio
      (SNR) in vivo. Thus, combined with the good stability, high biocompatibility and
      minimal toxicity properties, the obtained sMoSe2-ICG NSs hybrid has bright
      prospects for use in future PAI/PTT clinical applications.

PMID- 29633768
TI  - How graphene crosses a grain boundary on the catalyst surface during chemical
      vapour deposition growth.
AB  - The chemical vapour deposition (CVD) growth of graphene is normally an epitaxial
      process, where the atomic structure of the adlayer should copy the texture of the
      substrate. However, it has been widely observed that single crystalline graphene
      grown on metal foil may cross a grain boundary (GB) of the substrate without
      forming any line defect, a necessary condition to change its crystalline
      orientation and maintain the structure registry with the substrate on the other
      side of the GB. Here, we present a comprehensive theoretical study on graphene
      growth behavior on polycrystalline metal substrates. Our density functional
      theory (DFT) calculations reveal that for graphene growth on most metal surfaces,
      the binding energy difference between the epitaxial and non-epitaxial graphene on
      the substrate is not large enough to compensate for the formation energy of a GB
      in graphene and therefore, during the CVD process, the growing graphene can pass
      through a GB on the metal surface without changing its crystalline orientation.
      Hence, graphene CVD growth cannot be strictly regarded as an epitaxial process;
      this conclusion is further verified by atomic simulations. The present study
      shows that the growth of graphene on a metal catalyst surface should be regarded
      rather as a quasi-epitaxial process, where a graphene domain is aligned only on
      the single crystalline metal facet on which it nucleates, but this structural
      registry with the metal substrate may be lost when the graphene crosses a GB on
      the metal surface.

PMID- 29633761
TI  - Publisher Correction: Evidence that breast cancer risk at the 2q35 locus is
      mediated through IGFBP5 regulation.
AB  - This corrects the article DOI: 10.1038/ncomms5999.

PMID- 29633769
TI  - Manganese catalyzed reductive amination of aldehydes using hydrogen as a
      reductant.
AB  - A one-pot two-step procedure was developed for the alkylation of amines via
      reductive amination of aldehydes using molecular dihydrogen as a reductant in the
      presence of a manganese pyridinyl-phosphine complex as a pre-catalyst. After the
      initial condensation step, the reduction of imines formed in situ is performed
      under mild conditions (50-100  degrees C) with 2 mol% of catalyst and 5 mol% of
      tBuOK under 50 bar of hydrogen. Excellent yields (>90%) were obtained for a large
      combination of aldehydes and amines (40 examples), including aliphatic aldehydes
      and amino-alcohols.

PMID- 29633771
TI  - Enantioselective amination of nitroolefins under base-free and water-rich
      conditions using chiral bifunctional phase-transfer catalysts.
AB  - The direct enantioselective amination of nitroolefins has been performed with l
      tert-leucine-derived squaramide-scaffold bifunctional phase-transfer catalysts
      under base-free and water-rich conditions with low catalyst loading (0.5-1 mol%)
      to provide 2-aminonitroalkanes in good yields (up to 96%) and
      enantioselectivities (up to 93% ee).

PMID- 29633772
TI  - Chiral proton-transfer shuttle catalysts for carbene insertion reactions.
AB  - Transition metal-catalyzed carbene insertion into X-H bonds (X = N, O, S, and C)
      represents a typical carbene transfer reaction and has been widely used in
      organic synthesis. The enantioselectivity-determining step in some of these
      insertion reactions is the proton transfer of active intermediates such as
      ylides, metal enolates, or free enols. Since most of the traditional chiral
      transition metal catalysts tend to dissociate from these active intermediates and
      cannot be involved in the proton-transfer step, enantiocontrol of these insertion
      reactions has long been a challenging task. Since 2011, we have developed chiral
      spiro phosphoric acids as chiral proton-transfer shuttle (CPTS) catalysts, which
      have been proven to be efficient catalysts for the proton transfer of active
      intermediates in carbene insertion reactions. Upon combining with achiral
      dirhodium catalysts, the CPTS catalysts accomplish highly enantioselective
      insertions of N-H, S-H, and C-H bonds. Herein, a number of important chiral
      building blocks, including alpha-amino acid derivatives, alpha-amino ketones,
      alpha-thioesters, and alpha,alpha-diaryl acetates, were prepared with high yields
      and high enantioselectivities through these insertion reactions.

PMID- 29633773
TI  - Secondary amine salt catalyzed controlled activation of 2-deoxy sugar lactols
      towards alpha-selective dehydrative glycosylation.
AB  - A new organocatalytic glycosylation method exploiting the lactol functionality
      has been disclosed. The catalytic generation of glycosyl oxacarbenium ions from
      lactols under forcible conditions via weakly Bronsted-acidic, readily available
      secondary amine salts affects the diastereoselective glycosylation of 2
      deoxypyranoses and furanoses. This operationally simple iminium catalyzed
      activation of 2-deoxy hemi-acetals is a potential alternative to the existing
      cumbersome methods that need specialized handling. The mechanisms for this unique
      transformation and kinetic/thermodynamic effects have been discussed based on
      both experimental evidence and theoretical studies.

PMID- 29633775
TI  - Observation of current rectification by a new asymmetric iron(iii) surfactant in
      a eutectic GaIn|LB monolayer|Au sandwich.
AB  - In this paper we expand on the search for molecular rectifiers of electrical
      current and report on a hexacoordinate metallosurfactant [FeIII(LN3O)(OMe)2],
      where (LN3O)- is the deprotonated form of the new asymmetric ligand 2-((E)-((4,5
      bis(2-methoxyethoxy)-2-(((E)-pyridin-2-ylmethylene)amino)phenyl)imino)methyl)-4,6
      di-tert-butyl-phenol. This species rectifies current when deposited as a Langmuir
      Blodget film in a "EGaIn/Ga2O3|LB|Au" sandwich with rectification ratios ranging
      from 25 to 300 at 1 Volt.

PMID- 29633776
TI  - Anion-dependent thermo-responsive supramolecular superstructures of Cu(ii)
      macrocycles.
AB  - This investigation highlights the role of counter anion towards the formation of
      thermo-responsive supramolecular assemblies of pre-defined discrete molecular
      Cu(ii) macrocycles. A new heteroditopic ligand (L) composed of two terminal
      triazolyl-pyridine units and a central pyridine-2,6-carboxamide unit connected
      via ethylene spacers predominantly forms dinuclear Cu(ii) macrocycles [L2Cu2]X4
      (X = ClO4-, NO3-, Cl-) in the presence of respective monoanion-based Cu2+ salts.
      In contrast, dianionic SO42--based Cu2+ salt produces a mixture of both dinuclear
      [L2Cu2(SO4)2] and mononuclear [LCu(SO4)] Cu(ii) macrocycles. Importantly,
      detailed molecular structure determinations revealed the presence of multiple
      secondary interactions of the different counter anions with the corresponding
      macrocycles. The field emission scanning electron microscopy (FESEM) studies
      confirmed the ability of the individual macrocycles to further assemble upon slow
      evaporation of the solvent. Morphologically pure rod, sphere, and sheet-like
      superstructures were obtained for ClO4-, NO3-, and Cl- monoanion-based
      macrocycles, respectively. In contrast, a mixture of linear ribbon and
      microflower-like assemblies were obtained for SO42--based macrocycles. Moreover,
      it was found that upon heating, the rod-like assembly of [L2Cu2](ClO4)4 was
      gradually transformed into nanoparticles through a microparticle formation, which
      regenerated the rod-like assembly upon standing at room temperature. This was
      established from the FESEM, atomic force microscopy (AFM), and dynamic light
      scattering (DLS) studies.

PMID- 29633777
TI  - Shell-corona microgels from double interpenetrating networks.
AB  - Polymer microgels with a dense outer shell offer outstanding features as
      universal carriers for different guest molecules. In this paper, microgels formed
      by an interpenetrating network comprised of collapsed and swollen subnetworks are
      investigated using dissipative particle dynamics (DPD) computer simulations, and
      it is found that such systems can form classical core-corona structures, shell
      corona structures, and core-shell-corona structures, depending on the subchain
      length and molecular mass of the system. The core-corona structures consisting of
      a dense core and soft corona are formed at small microgel sizes when the
      subnetworks are able to effectively separate in space. The most interesting shell
      corona structures consist of a soft cavity in a dense shell surrounded with a
      loose corona, and are found at intermediate gel sizes; the area of their
      existence depends on the subchain length and the corresponding mesh size. At
      larger molecular masses the collapsing network forms additional cores inside the
      soft cavity, leading to the core-shell-corona structure.

PMID- 29633774
TI  - C-C bond forming radical SAM enzymes involved in the construction of carbon
      skeletons of cofactors and natural products.
AB  - Covering: up to the end of 2017 C-C bond formations are frequently the key steps
      in cofactor and natural product biosynthesis. Historically, C-C bond formations
      were thought to proceed by two electron mechanisms, represented by Claisen
      condensation in fatty acids and polyketide biosynthesis. These types of
      mechanisms require activated substrates to create a nucleophile and an
      electrophile. More recently, increasing number of C-C bond formations catalyzed
      by radical SAM enzymes are being identified. These free radical mediated
      reactions can proceed between almost any sp3 and sp2 carbon centers, allowing
      introduction of C-C bonds at unconventional positions in metabolites. Therefore,
      free radical mediated C-C bond formations are frequently found in the
      construction of structurally unique and complex metabolites. This review
      discusses our current understanding of the functions and mechanisms of C-C bond
      forming radical SAM enzymes and highlights their important roles in the
      biosynthesis of structurally complex, naturally occurring organic molecules.
      Mechanistic consideration of C-C bond formation by radical SAM enzymes identifies
      the significance of three key mechanistic factors: radical initiation, acceptor
      substrate activation and radical quenching. Understanding the functions and
      mechanisms of these characteristic enzymes will be important not only in
      promoting our understanding of radical SAM enzymes, but also for understanding
      natural product and cofactor biosynthesis.

PMID- 29633780
TI  - Refolding of helical soluble alpha-synuclein through transient interaction with
      lipid interfaces.
AB  - alpha-Synuclein (alphaSyn) is a key player in the pathogenesis of Parkinson's
      disease and other synucleinopathies. Here, we report the existence of a novel
      soluble alpha-helical conformer of alphaSyn, obtained through transient
      interaction with lipid interfaces, and propose dynamic oligomerization as the
      mechanism underlying its stability. The conformational space of alphaSyn appears
      to be highly context-dependent, and lipid bilayers might thus play crucial roles
      as molecular chaperones in a cellular environment.

PMID- 29633781
TI  - A prefatory note for the 50th anniversary of The Japanese Society for
      Neurochemistry.

PMID- 29633783
TI  - Honey for acute cough in children.
AB  - BACKGROUND: Cough causes concern for parents and is a major cause of outpatient
      visits. Cough can impact quality of life, cause anxiety, and affect sleep in
      children and their parents. Honey has been used to alleviate cough symptoms. This
      is an update of reviews previously published in 2014, 2012, and 2010. OBJECTIVES:
      To evaluate the effectiveness of honey for acute cough in children in ambulatory
      settings. SEARCH METHODS: We searched CENTRAL (2018, Issue 2), which includes the
      Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (2014
      to 8 February 2018), Embase (2014 to 8 February 2018), CINAHL (2014 to 8 February
      2018), EBSCO (2014 to 8 February 2018), Web of Science (2014 to 8 February 2018),
      and LILACS (2014 to 8 February 2018). We also searched ClinicalTrials.gov and the
      World Health Organization International Clinical Trial Registry Platform (WHO
      ICTRP) on 12 February 2018. The 2014 review included searches of AMED and CAB
      Abstracts, but these were not searched for this update due to lack of
      institutional access. SELECTION CRITERIA: Randomised controlled trials comparing
      honey alone, or in combination with antibiotics, versus no treatment, placebo,
      honey-based cough syrup, or other over-the-counter cough medications for children
      aged 12 months to 18 years for acute cough in ambulatory settings. DATA
      COLLECTION AND ANALYSIS: We used standard methodological procedures expected by
      Cochrane. MAIN RESULTS: We included six randomised controlled trials involving
      899 children; we added three studies (331 children) in this update.We assessed
      two studies as at high risk of performance and detection bias; three studies as
      at unclear risk of attrition bias; and three studies as at unclear risk of other
      bias.Studies compared honey with dextromethorphan, diphenhydramine, salbutamol,
      bromelin (an enzyme from the Bromeliaceae (pineapple) family), no treatment, and
      placebo. Five studies used 7-point Likert scales to measure symptomatic relief of
      cough; one used an unclear 5-point scale. In all studies, low score indicated
      better cough symptom relief.Using a 7-point Likert scale, honey probably reduces
      cough frequency better than no treatment or placebo (no treatment: mean
      difference (MD) -1.05, 95% confidence interval (CI) -1.48 to -0.62; I2 = 0%; 2
      studies; 154 children; moderate-certainty evidence; placebo: MD -1.62, 95% CI 
      3.02 to -0.22; I2 = 0%; 2 studies; 402 children; moderate-certainty evidence).
      Honey may have a similar effect as dextromethorphan in reducing cough frequency
      (MD -0.07, 95% CI -1.07 to 0.94; I2 = 87%; 2 studies; 149 children; low-certainty
      evidence). Honey may be better than diphenhydramine in reducing cough frequency
      (MD -0.57, 95% CI -0.90 to -0.24; 1 study; 80 children; low-certainty
      evidence).Giving honey for up to three days is probably more effective in
      relieving cough symptoms compared with placebo or salbutamol. Beyond three days
      honey probably had no advantage over salbutamol or placebo in reducing cough
      severity, bothersome cough, and impact of cough on sleep for parents and children
      (moderate-certainty evidence). With a 5-point cough scale, there was probably
      little or no difference between the effects of honey and bromelin mixed with
      honey in reducing cough frequency and severity.Adverse events included
      nervousness, insomnia, and hyperactivity, experienced by seven children (9.3%)
      treated with honey and two children (2.7%) treated with dextromethorphan (risk
      ratio (RR) 2.94, 95% Cl 0.74 to 11.71; I2 = 0%; 2 studies; 149 children; low
      certainty evidence). Three children (7.5%) in the diphenhydramine group
      experienced somnolence (RR 0.14, 95% Cl 0.01 to 2.68; 1 study; 80 children; low
      certainty evidence). When honey was compared with placebo, 34 children (12%) in
      the honey group and 13 (11%) in the placebo group complained of gastrointestinal
      symptoms (RR 1.91, 95% CI 1.12 to 3.24; I2 = 0%; 2 studies; 402 children;
      moderate-certainty evidence). Four children who received salbutamol had rashes
      compared to one child in the honey group (RR 0.19, 95% CI 0.02 to 1.63; 1 study;
      100 children; moderate-certainty evidence). No adverse events were reported in
      the no-treatment group. AUTHORS' CONCLUSIONS: Honey probably relieves cough
      symptoms to a greater extent than no treatment, diphenhydramine, and placebo, but
      may make little or no difference compared to dextromethorphan. Honey probably
      reduces cough duration better than placebo and salbutamol. There was no strong
      evidence for or against using honey. Most of the children received treatment for
      one night, which is a limitation to the results of this review. There was no
      difference in occurrence of adverse events between the honey and control arms.

PMID- 29633784
TI  - Optical correction of refractive error for preventing and treating eye symptoms
      in computer users.
AB  - BACKGROUND: Computer users frequently complain about problems with seeing and
      functioning of the eyes. Asthenopia is a term generally used to describe symptoms
      related to (prolonged) use of the eyes like ocular fatigue, headache, pain or
      aching around the eyes, and burning and itchiness of the eyelids. The prevalence
      of asthenopia during or after work on a computer ranges from 46.3% to 68.5%.
      Uncorrected or under-corrected refractive error can contribute to the development
      of asthenopia. A refractive error is an error in the focusing of light by the eye
      and can lead to reduced visual acuity. There are various possibilities for
      optical correction of refractive errors including eyeglasses, contact lenses and
      refractive surgery. OBJECTIVES: To examine the evidence on the effectiveness,
      safety and applicability of optical correction of refractive error for reducing
      and preventing eye symptoms in computer users. SEARCH METHODS: We searched the
      Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; Embase; Web of
      Science; and OSH update, all to 20 December 2017. Additionally, we searched trial
      registries and checked references of included studies. SELECTION CRITERIA: We
      included randomised controlled trials (RCTs) and quasi-randomised trials of
      interventions evaluating optical correction for computer workers with refractive
      error for preventing or treating asthenopia and their effect on health related
      quality of life. DATA COLLECTION AND ANALYSIS: Two authors independently assessed
      study eligibility and risk of bias, and extracted data. Where appropriate, we
      combined studies in a meta-analysis. MAIN RESULTS: We included eight studies with
      381 participants. Three were parallel group RCTs, three were cross-over RCTs and
      two were quasi-randomised cross-over trials. All studies evaluated eyeglasses,
      there were no studies that evaluated contact lenses or surgery. Seven studies
      evaluated computer glasses with at least one focal area for the distance of the
      computer screen with or without additional focal areas in presbyopic persons. Six
      studies compared computer glasses to other types of glasses; and one study
      compared them to an ergonomic workplace assessment. The eighth study compared
      optimal correction of refractive error with the actual spectacle correction in
      use. Two studies evaluated computer glasses in persons with asthenopia but for
      the others the glasses were offered to all workers regardless of symptoms. The
      risk of bias was unclear in five, high in two and low in one study. Asthenopia
      was measured as eyestrain or a summary score of symptoms but there were no
      studies on health-related quality of life. Adverse events were measured as
      headache, nausea or dizziness. Median asthenopia scores at baseline were about
      30% of the maximum possible score.Progressive computer glasses versus monofocal
      glassesOne study found no considerable difference in asthenopia between various
      progressive computer glasses and monofocal computer glasses after one-year follow
      up (mean difference (MD) change scores 0.23, 95% confidence interval (CI) -5.0 to
      5.4 on a 100 mm VAS scale, low quality evidence). For headache the results were
      in favour of progressive glasses.Progressive computer glasses with an
      intermediate focus in the upper part of the glasses versus other glassesIn two
      studies progressive computer glasses with intermediate focus led to a small
      decrease in asthenopia symptoms (SMD -0.49, 95% CI -0.75 to -0.23, low-quality
      evidence) but not in headache score in the short-term compared to general purpose
      progressive glasses. There were similar small decreases in dizziness. At medium
      term follow-up, in one study the effect size was not statistically significant
      (SMD -0.64, 95% CI -1.40 to 0.12). The study did not assess adverse
      events.Another study found no considerable difference in asthenopia between
      progressive computer glasses and monofocal computer glasses after one-year follow
      up (MD change scores 1.44, 95% CI -6.95 to 9.83 on a 100 mm VAS scale, very low
      quality evidence). For headache the results were inconsistent.Progressive
      computer glasses with far-distance focus in the upper part of the glasses versus
      other glassesOne study found no considerable difference in number of persons with
      asthenopia between progressive computer glasses with far-distance focus and
      bifocal computer glasses after four weeks' follow-up (OR 1.00, 95% CI 0.40 to
      2.50, very low quality evidence). The number of persons with headache, nausea and
      dizziness was also not different between groups.Another study found no
      considerable difference in asthenopia between progressive computer glasses with
      far-distance focus and monofocal computer glasses after one-year follow-up (MD
      change scores -1.79, 95% CI -11.60 to 8.02 on a 100 mm VAS scale, very low
      quality evidence). The effects on headaches were inconsistent.One study found no
      difference between progressive far-distance focus computer glasses and trifocal
      glasses in effect on eyestrain severity (MD -0.50, 95% CI -1.07 to 0.07, very low
      quality evidence) or on eyestrain frequency (MD -0.75, 95% CI -1.61 to 0.11, very
      low quality evidence).Progressive computer glasses versus ergonomic assessment
      with habitual (computer) glassesOne study found that computer glasses optimised
      for individual needs reduced asthenopia sum score more than an ergonomic
      assessment and habitual (computer) glasses (MD -8.9, 95% CI -16.47 to -1.33,
      scale 0 to 140, very low quality evidence) but there was no effect on the
      frequency of eyestrain (OR 1.08, 95% CI 0.38 to 3.11, very low quality
      evidence).We rated the quality of the evidence as low or very low due to risk of
      bias in the included studies, inconsistency in the results and imprecision.
      AUTHORS' CONCLUSIONS: There is low to very low quality evidence that providing
      computer users with progressive computer glasses does not lead to a considerable
      decrease in problems with the eyes or headaches compared to other computer
      glasses. Progressive computer glasses might be slightly better than progressive
      glasses for daily use in the short term but not in the intermediate term and
      there is no data on long-term follow-up. The quality of the evidence is low or
      very low and therefore we are uncertain about this conclusion. Larger studies
      with several hundreds of participants are needed with proper randomisation,
      validated outcome measurement methods, and longer follow-up of at least one year
      to improve the quality of the evidence.

PMID- 29633785
TI  - Analysis of fentanyl analogs and novel synthetic opioids in blood, serum/plasma,
      and urine in forensic casework.
AB  - In recent years an increasing number of novel opioids have appeared on the
      illicit drug market and have been linked to the growing opioid crisis in the
      United States. It is suspected that synthetic-opioid-related deaths are
      underestimated since many laboratories either use a screening method that is not
      specific and sensitive enough for these compounds or testing is not performed for
      fentanyl and its related analogs in general. We describe a method for the
      analysis of 19 of the most current novel opioid drugs quantitatively in whole
      blood and serum, and 17 analytes qualitatively in urine using solid phase
      extraction with liquid chromatography-tandem mass spectrometry (LC-MS/MS). The
      limit of detection was determined to be at a minimum 0.25 ng/mL for beta
      hydroxythiofentanyl, 0.05 ng/mL for butyryl/isobutyrylfentanyl, AH-7921, 2
      furanylfentanyl, 4-ANPP, and U-47700; 0.025 ng/mL for MT-45, para
      methoxybutyrylfentanyl, 4-methylphenethyl acetyl fentanyl, U-50488,
      acrylfentanyl, valerylfentanyl, and carfentanil; and 0.0125 ng/mL for para
      fluorofentanyl, ortho-fluorofentanyl, para-fluorobutyrylfentanyl/FIBF, and alpha
      methylfentanyl. The lower limit of quantitation was determined to be 0.1 ng/mL
      for all analytes except AH-7921, U-47700, U-50488 which were 0.05 ng/mL and beta
      hydroxythiofentanyl which was 0.5 ng/mL. The method was validated successfully
      according to a Scientific Working Group in Forensic Toxicology (SWGTOX) compliant
      approach. This method was applied to the analysis of 2758 samples between October
      2016 and September 2017. It was determined that 4-ANPP, furanylfentanyl, and
      carfentanil were the 3 most prevalent fentanyl related compounds detected: 56.1%
      of cases were positive for 4-ANPP, 44.5% were positive for furanylfentanyl, and
      25.2% cases were positive for carfentanil.

PMID- 29633786
TI  - Vascular Anomalies of the Orbit--A Reappraisal.
AB  - The recent International Society for the Study of Vascular Anomalies (ISSVA)
      classification of vascular anomalies can be applied to orbital lesions, dividing
      them into vascular tumors and vascular malformations. Orbital cavernous
      hemangiomas are probably best considered cavernous venous malformations under
      this classification. Management of symptomatic lesions can be with surgical
      excision or stereotactic fractionated radiotherapy in selected cases. Beta
      blockers including propranolol and topical timolol maleate represent first-line
      therapy for infantile hemangiomas, although surgery has a role in selected cases.
      Orbital venous-lymphatic malformations are problematic but with improved imaging,
      neuroradiological intervention, and a multidisciplinary approach to management,
      outcomes are improving.

PMID- 29633787
TI  - miR-31 and miR-145 as Potential Non-Invasive Regulatory Biomarkers in Patients
      with Endometriosis.
AB  - This article published in Cell J (Yakhteh), Vol 20, No 1, Apr-Jun 2018, on pages
      84-89, the labels of columns in "Figure 3B" was changed. The correct one is
      presented below.

PMID- 29633788
TI  - The impact of a structured intensive modular training in the learning curve of
      robot assisted radical prostatectomy.
AB  - AIM: The success of Robot Assisted Laparoscopic Prostatectomy (RALP) is mainly
      due to his relatively short learning curve. Twenty cases are needed to reach a "4
      hours-proficiency". However, to achieve optimal functional outcomes such as
      urinary continence and potency recovery may require more experience. We aim to
      report the perioperative and early functional outcomes of patients undergoing
      RALP, after a structured modular training program. METHODS: A surgeon with no
      previous laparoscopic or robotic experience attained a 3 month modular training
      including: a) e-learning; b) assistance and training to the operating table; c)
      dry console training; d) step by step in vivo modular training performing 40
      surgical steps in increasing difficulty, under the supervision of an experienced
      mentor. Demographics, intraoperative and postoperative functional outcomes were
      recorded after his first 120 procedures, considering four groups of 30 cases.
      RESULTS: All procedures were completed successfully without conversion to open
      approach. Overall 19 (15%) post operative complications were observed and 84%
      were graded as minor (Clavien I-II). Overall operative time and console time
      gradually decreased during the learning curve, with statistical significance in
      favour of Group 4. The overall continence rate at 1 and 3 months was 74% and 87%
      respectively with a significant improvement in continence rate throughout the
      four groups (p = 0.04). Considering those patients submitted to nerve-sparing
      procedure we found a significant increase in potency recovery over the four
      groups (p = 0.04) with the higher potency recovery rate up to 80% in the last 30
      cases. CONCLUSIONS: Optimal perioperative and functional outcomes have been
      attained since early phase of the learning curve after an intensive structured
      modular training and less than 100 consecutive procedures seem needed in order to
      achieve optimal urinary continence and erectile function recovery.

PMID- 29633789
TI  - Injection therapy for chronic prostatitis: A retrospective analysis of 77 cases.
AB  - OBJECTIVE: To compare pre- and post-therapy symptom scores reported on the
      National Institute of Health Chronic Prostatitis Symptom Index (NIHCPSI) after
      trans-rectal antibiotic injections therapy for men suffering from chronic
      prostatitis. MATERIALS AND METHODS: Retrospective analysis of NIHCPSI symptom
      scores obtained from chart reviews of 77 treated males suffering from chronic
      prostatitis before and after trans rectal injections for the treatment of chronic
      prostatitis. RESULTS: Most patients reported a 40% to 60% improvement in symptom
      scores. In subgroups comparing scores in patients with less than 5 injections,
      the improvement was less than in patients who received 10 or more injections.
      Patients' responses after a shorter (3 months) follow up showed better pain
      scores than patient's scores after longer, over one-year or more, follow- up
      periods. CONCLUSION: Our findings show that direct antibiotic injection for
      chronic prostatitis is a viable addition to standard therapies. Improvements in
      symptom scores are long lasting. Discomfort is minimal and side effects are rare
      and avoidable.

PMID- 29633790
TI  - The impact of prostate artery embolization (PAE) on the the physical history and
      pathophysiology of benign prostatic hyperplasia (BPH).
AB  - AIM: Prostate artery embolization (PAE) is a non invasive modality for the
      treatment of benign prostate hypertrophy (BPH) related lower urinary tract
      symptoms (LUTS). As a relatively new procedure, data determining the clinical
      success is somehow scarce. In the present article we examine the current clinical
      outcome measures in order to identify the most accurate. RESULTS: Current imaging
      outcome measures are consistent with clinical ones only in the group of patients
      with adenomatous- dominant BPH while are inconsistent in patients with small
      sized adenomas. CONCLUSIONS: Additional studies and/or evaluation tools are
      needed in order to provide accurate evaluation of clinical success in the
      subgroup of patients with non- adenomatous-dominant BPH while they may inspire
      new options and novel techniques for both BPH treatment and treatment-follow up.

PMID- 29633791
TI  - Pathology outcomes in patients with transurethral bladder tumour resection in a
      Turkish population: A retrospective analysis.
AB  - OBJECTIVES: Transurethral bladder tumour resection (TURBT) is the common surgical
      method used in the diagnosis, staging and treatment of patients with bladder
      tumour. Most of the rare tumours other than the urothelial carcinomas of the
      bladder are in advanced stage on diagnosis and necessitate aggressive treatment.
      In our study, we aimed to the histologic types of bladder cancer and to determine
      the regional incidence of rare bladder cancer types in our region. MATERIALS AND
      METHODS: We retrospectively evaluated 815 patients who underwent TURBT surgery
      between January 2010 and March 2016 in our clinic with a diagnosis of bladder
      cancer and at least 1 year follow-up. Patients with tumour histopathological
      examination including histological tumour type, grade and were reported. Thirty
      nine patients with an unclear pathology report (neighboring organ invasion,
      cautery artifact, etc) and 17 patients whose data could not be accessed were
      excluded from the study. The patients who had received chemotherapy or
      radiotherapy due to any type of malignancy (23) were also excluded from the
      study. RESULTS: The outcomes of 736 patients operated in our clinics due to
      bladder tumour were evaluated. The mean age was 65.2 +/- 8.4; 135 were female and
      601 were male. Among them 711 patients with urothelial carcinoma were reported
      (94.2%). According to TNM classification, stage Ta was observed in 270 patients
      (37.9%), stage T1 in 297 (41.7%), and stage T2 in 144 (20.3%). Non-urothelial
      cancers were reported in 25 cases (3.3%). CONCLUSION: The incidence of bladder
      carcinoma varies between regions. The results of our study are similar to those
      of the western countries. Increased smoking and exposure to environmental
      carcinogenetic agents may lead to altered incidences and histological types of
      bladder tumours. Revision of regional tumour records may be useful to develop and
      evaluate future treatment strategies.

PMID- 29633792
TI  - Intravesical administration of combined hyaluronic acid and chondroitin sulfate
      can improve symptoms in patients with refractory bacillus Calmette-Guerin-induced
      chemical cystitis: Preliminary experience with one-year follow-up.
AB  - OBJECTIVE: We investigated the efficacy of intravesical instillations of combined
      hyaluronic acid (HA) and chondroitin sulphate (CS) in patients with bacillus
      Calmette-Guerin (BCG)-induced chemical cystitis unresponsive to first-line
      therapies. PATIENTS AND METHODS: We retrospectively reviewed the clinical records
      of patients with grade 2 BCG-induced chemical cystitis unresponsive to first line
      therapeutic options performed according to the International Bladder Cancer Group
      guidelines who underwent intravesical instillations of HA/CS. Bladder pain,
      urinary urgency, voiding volume and number of voids/24 hours recorded prior to
      treatment, at the end of the treatment, at six months and at one-year follow-up
      were recorded and analyzed. RESULTS: The records of 20 patients were identified.
      All patients underwent eight weekly instillations of HA/CS. Mean baseline visual
      analogue scale (VAS) scores +/- Standard Deviation (SD) for urinary urgency and
      bladder pain were 7.8 +/- 0.5 and 7.2 +/- 1.0, respectively. Mean number of
      voids/24 hours +/- SD was 15.4 +/- 2.3 and mean urine volume per void +/- SD was
      85.8 +/- 21.0 mL. At the end of the treatment, mean VAS scores +/- SD for urgency
      and pain significantly decreased to 4.7 +/- 1.1 and 4.2 +/- 0.9, respectively (p
      < 0.05 in both cases). Mean number of voids/24 hours +/- SD decreased to 9.6 +/-
      1.4 (p < 0.05) and mean urine volume per void +/- SD significantly increased to
      194.1 +/- 59.5 mL (p < 0.05). At six months and one-year followup, all outcome
      measures remained stable. CONCLUSIONS: Bladder instillations of HA/CS provide
      significant and durable improvement of bladder pain, urinary urgency, urinary
      volume per void and urinary frequency in patients with refractory BCG-induced
      chemical cystitis.

PMID- 29633793
TI  - The impact of ureteral Double-J stent insertion following ureterorenoscopy in
      patients with ureteral stones accompanied by perirenal fat stranding.
AB  - OBJECTIVE: To evaluate the impact of ureteral stent insertion following semirigid
      ureterorenoscopy (URS) in patients with perirenal fat stranding (PFS) due to
      ureteral stones. MATERIAL AND METHODS: Data of 600 patients who underwent URS
      were analyzed retrospectively. Seventy-two patients detected to have PFS
      accompanying ureteral stone were included. Patients who did not undergo double J
      (DJ) stent insertion following semirigid URS were classified as Group I (n: 52),
      while those who underwent stent insertion were classified as Group II (n: 20).
      Side distribution; localization of the stones, stone size, presence of fever,
      urinary tract infection (UTIs) and urosepsis rates were compared in the two
      groups. RESULTS: The average age of the patients was 44.4 (20-71) years.
      Male/female ratio and side of the stone location showed similar distribution in
      both groups (p > 0.05). Fever occurred in 23 cases (44.2%) in Group I and in 15
      cases (75%) in Group II (p = 0.038). UTIs occurred in 15 cases (28.9%) in Group I
      and in 12 cases (60%) in Group II (p = 0.03). Urosepsis presented in 3 (5.8%) and
      5 (25%) of the patients in Group I and II, respectively (p = 0.033). CONCLUSIONS:
      According to our results, ureteral DJ stent insertion following URS in patients
      with PFS due to ureteral stone caused an increase on postoperative infection
      related complications.

PMID- 29633794
TI  - Semirigid ureteroscopy prior retrograde intrarenal surgery (RIRS) helps to select
      the right ureteral access sheath.
AB  - OBJECTIVE: To evaluate ureteral compliance through semirigid ureteroscopy (sURS)
      in order to select the proper ureteral access sheath (UAS) size for retrograde
      intrarenal surgery (RIRS). PATIENTS AND METHODS: In a prospective study, 100
      consecutive patients selected for elective sURS or RIRS were recruited. Each
      patient, initially underwent 9.5 Fr sURS with a safety guidewire 3Fr, in order to
      estimate ureteral compliance. If the ureter was compliant, a gently passage of a
      12/14Fr UAS was attempted. If the ureter was not deemed compliant, passage of
      either a smaller UAS or a smaller semirigid 7Fr or a flexible 7.5Fr or a digital
      8.5Fr scope with and without safety guidewire, was attempted. Age, gender,
      disease location, prestenting, previous RIRS and/or stone elimination,
      hydronephrosis, ureteral strictures, unsuccessful procedures, and complications,
      were analyzed as possible correlated factors of ureteral compliance. RESULTS: In
      77 patients the ureter was deemed compliant >= 14Fr. Of the preoperative factors
      that were examined, stent placement before RIRS (P < 0.002), previous RIRS (P =
      0.000) and previous stone elimination (P = 0.004), correlated with ureter >=
      14Fr. Ureteral lithiasis (P < 0.001), ureteral strictures (P < 0.05),
      unsuccessful procedures (P < 0.005) and complications (P = 0.01) correlated with
      ureter < 14Fr. The complication rate was 10% (10 patients) with ureteral injuries
      grade I in 9 patients and grade III in 1 patient according to the endoscopic
      grading system. Age, gender, hydronephrosis and urothelial carcinoma (UC) had no
      influence. CONCLUSIONS: sURS performed before RIRS allows selection of the right
      ureteral access sheath (UAS) and avoidance of major complications. Pre-stenting,
      previous RIRS and stone elimination history are all factors correlating with a
      compliant ureter.

PMID- 29633795
TI  - Comparison of three most frequently used alpha blocker agents in medical
      expulsive therapy for distal ureteral calculi, result of a retrospective
      observational study.
AB  - PURPOSE: In this study, we compared the effects of three agents frequently used
      in daily life for medical expulsive therapy. MATERIALS AND METHODS: A total of
      143 patients meeting the criteria were included in the study. Patients were
      divided into three homogeneous drug groups which were tamsulosin group (n:48),
      alfuzosin group (n:47) and silodosin group (n:48). The time of stone expulsion,
      analgesic needs, side effects of the medicine and endoscopic intervention needs
      of the patients were recorded. RESULTS: The rate of stone expulsion was 70.8%
      (n:34) in tamsulosin group, 70.2% (n:33) in alfuzosin group, and 75% (n:36) in
      silodosin group. No significant difference was observed among the rates of stone
      expulsion in three groups, and the rates of stone expulsion were similar (p =
      0.778). The duration of stone expulsion was significantly different in the groups
      (p = 0.012): the time of stone expulsion for tamsulosin was 2.33 +/- 0.78 days
      longer than for Silodosin, indicating a significant difference. There was no
      significant difference between tamsulosin-alfuzosin and silodosin-alfuzosin
      (respectively p = 0.147, p = 0.925). CONCLUSIONS: The results of this study
      showed that medical expulsive therapy by using alpha blocker agents is safe and
      efficacious. This option must be kept in mind for patients who do not ask for
      surgery as the first-step treatment for eligible patients.

PMID- 29633796
TI  - A new technique of ultrasound guided percutaneous renal biopsy by perforated
      probe and perpendicular needle trajectory.
AB  - The percutaneous biopsy of native kidneys according to the classical methodology
      is performed under real time ultrasound guidance with the needle introduction
      along a trajectory of about 30 degrees , aimed to the lower pole of the kidney.
      Recently, a variant of the classical technique has been introduced by which a
      perforated ultrasound probe is used to guide the needle along a perpendicular
      trajectory to the terminal section of the lower kidney pole where the front and
      back margins of the cortical kidney tissue join each other without renal sinus
      interposition so to offer to the needle a 3-4 cm thick cortical tissue front
      which allows to obtain a cortical tissue sample suitable for histological
      examination even with a single needle pass, while at the same time limiting the
      possibility of damaging the smaller kidney calices of the lower group whose
      lesion causes hematuria. In this paper, we present a large survey (50 patients)
      to compare to data from the literature obtained by using similar needle gauge and
      with a similar follow-up period after biopsy. The result of this comparison
      confirms the efficacy of this variant of the classical technique because in front
      of a statistically lower number of needle passes, it allowed to obtain 100% of
      samples suitable for histological analysis, in absence of major complications and
      with a statistically lower post-biopsy hemoglobin drop in comparison to that
      observed in a group of 44 patients biopsied with a greater number of needle
      passes, in the only study of the literature which is directly comparable to our
      study in relation to needle gauge and duration of monitoring.

PMID- 29633797
TI  - Erectile dysfunction in patients taking psychotropic drugs and treated with
      phosphodiesterase-5 inhibitors.
AB  - OBJECTIVES: The aim of this study was to assess the prevalence of patients with
      Erectile Dysfunction (ED) receiving psychotropic drugs, the impact of these drugs
      on hormonal profile, and the efficacy of PDE5-i in these patients. MATERIALS AND
      METHODS: We recruited 1872 patients referring for ED to our Andrology Unit.
      Assessment included serum testosterone, gonadotropins, TSH, prolactin, and PSA,
      and the IIEF-5 questionnaire for ED diagnosis. Inclusion criteria were age 21-75
      years and IIEF-5 total score <= 21; exclusion criteria included hypogonadism,
      diabetes mellitus, previous prostatectomy, other medication intake, and ED
      diagnosis prior to psychotropic drug treatment. Efficacy was rated with the IIEF
      5 (remission: total score >= 22). RESULTS: The prevalence of ED patients treated
      with psychotropic drugs since >= 3 months was 9.5% (178/1872), subdivided
      according to the drugs used into: Group A, 16 patients treated with atypical
      antipsychotics (9.0%); Group B, 55 patients with benzodiazepines (30.9%); Group
      C, 33 patients with antidepressant drugs (18.5%); and Group D, 74 patients with
      multiple psychotropic drugs (41.6%). Patients in Group A were significantly
      younger than other groups (p < 0.05). The hormonal profile presented only higher
      prolactin level in patients treated with antipsychotics, alone or in combination
      (p < 0.05). Overall, 146 patients received PDE5-i. Remission rate, after three
      months of treatment, was significantly higher in Group B compared to C and D
      groups (p < 0.05). CONCLUSIONS: A substantial portion of patients receiving
      psychotropic drugs show ED. Sexual performance in these patients benefits from
      PDE5-i. Age, effects of psychiatric disorders, psychotropic drugs, and PDE5-i
      treatment modality accounted for variability of response in this sample.

PMID- 29633798
TI  - Seminal transferrin in the seminal quality evaluation of hemodialytic patients.
AB  - OBJECTIVE: to verify the association between seminal quality and seminal
      transferrin (ST) level and fertility index in patients undergoing chronic
      hemodialysis (CH). MATERIAL AND METHODS: This is a cross-sectional study in a
      group of 60 men (case) undergoing CH for more than 6 months, and a group of 30
      healthy men (control), aged 18-60 years, without clinical or laboratory signs of
      infection/inflammation. Spermiogram was performed, fertility index (FI) was
      calculated and ST and sex hormones (SH) levels were measured, including follicle
      stimulating hormone, luteinizing hormone, total testosterone, and prolactin.
      RESULTS: All individuals were eugonadal. No differences for age (49.47 +/- 5.56,
      47.90 +/- 6.2, p = 0.22) were observed between cases and controls, whereas there
      were significant differences between the individuals in the case and control
      groups with respect to the mean FI (p = 0.000), seminal parameters (SP) (p =
      0.000), and ST levels (40.12 +/- 08.25 vs 73.32 +/- 06.8, p = 0.000). ST levels
      were correlated with FI (r = 0.787, p = 0.00) and SP (motility: r = 0.857, p =
      0.000; vitality: r = 0.551, p = 0.000; density: r = 0.850, p = 0.000; normal
      morphology: r = 0.386, p = 0.000). Linear regression model showed relationship of
      ST levels with total sperm motility (R2 = 0.701; p = 0.000) and and FI (R2 =
      0.569; p = 0.000). CONCLUSIONS: Our results suggest that seminal quality is
      associated with ST levels and FI and that it can be used the initial
      investigation of subfertility/infertility of patients undergoing chronic
      hemodialysis..

PMID- 29633799
TI  - How do vegetable oils (hazelnut and canola) affect the reproductive system in
      male rats?
AB  - OBJECTIVE: Vegetable oils have an important place in our daily diet. This study
      starts from this point to investigate the effects of canola oil and hazelnut oil
      in the male reproductive system in rats. MATERIAL AND METHODS: 30 male rats were
      used in this 16-week study. The animals were divided into three groups: the
      animals in group I served as the control group, while the animals in group II and
      group III were fed with hazelnut and canola oil, respectively. The testes of all
      rats were excised for histopathologic evaluation and immunohistochemical (IHC)
      evaluation with a standard method. Blood samples were obtained for determination
      of serum hormone levels. RESULTS: No significant differences were noted with
      respect to behavior or weight among the three groups. Rats in the canola oil
      group (group III) had higher luteinizing hormone (LH) and higher testosterone
      levels than rats in the control group. Rats who received hazelnut oil (group II)
      exhibited similar findings, with these levels being higher than they were in the
      control group. No statistical differences were shown for histopathology or IHC
      testosterone antibody levels across all treatment groups. Conclussion: Canola oil
      was shown to have a greater effect on serum LH and testosterone compared to the
      control group and the group fed with hazelnut oil. Further investigation is
      required into how these oils affect serum hormone and sperm activity.

PMID- 29633800
TI  - The role of diallyl thiosulfinate associated with nuciferine and diosgenin in the
      treatment of premature ejaculation: A pilot study.
AB  - OBJECTIVE: To assess the efficacy and safety of an association of diallyl
      thiosulfinate with nuciferine and diosgenin in the treatment of a group of
      patients suffering from premature ejaculation (PE), primary or secondary to
      erectile dysfunction (ED). MATERIALS AND METHODS: From July 2015 to October 2016,
      143 patients (mean age 25.3; range 18-39) affected by PE completed the study and
      were finally analyzed in this phase I study. All patients, after clinical
      assessment and laboratory evaluation were asked to take an association of diallyl
      thiosulfinate with nuciferine and diosgenin as oral tablet, once a day, on
      alternate days, for three months. At the baseline and after three months of
      treatment, each patient was asked to complete the following questionnaires:
      International Index of Erectile Function (IIEF-5), Premature Ejaculation
      Diagnostic Tool (PEDT), Male Sexual Health Questionnaire (MSHQ). RESULTS: A
      statistical significant improvement in terms of erectile function, comparing the
      IIEF-5 value at baseline and follow- up visit was found (respectively IIEF-5: 8.7
      vs 14.01; p < 0.001). Moreover, at follow-up visit, 97/143 men (67.8%) referred a
      subjective improvement of the erection quality and a better control of the
      ejaculation (PROs). The IELT improved too between the baseline evaluation and the
      follow-up visit (p < 0.001). CONCLUSION: In conclusion, our study, even if
      supported by preliminary results, showed how Diallyl Thiosulfinate, Nuciferine
      and Diosgenin is able to improve the control of ejaculation in patients suffering
      from PE, primary or secondary to ED without any significant adverse effects.

PMID- 29633801
TI  - Robotic perineal radical prostatectomy with high prostate volume.
AB  - BACKGROUND: Minimally invasive techniques are ever improving and are preferred
      more. Many techniques were developed in radical prostatectomy operations. Robotic
      radical prostatectomy with the perineal approach is a new technique. CASE
      PRESENTATION: A 66-year-old male patient presented because of lower urinary tract
      symptoms, a PSA value of 5.5 ng/ml was detected, prostate biopsy was performed
      under transrectal ultrasound guide, a Gleason 3+3 adenocarcinoma on 3/12 foci was
      reported at pathology. Robotic perineal radical prostatectomy (r-PRP) operation
      was performed in the patient who had a prostate volume of 130 cc with middle lobe
      and a body mass index of 32 without additional disease. The duration of operation
      was 140 minutes in total and the duration at the console was 95 minutes, the
      amount of bleeding was 85 cc and no intraoperative complication was detected.
      CONCLUSION: r-PRP is a technique that can be applied safely without prolonging
      the operation period and without additional morbidity to the patient, preserving
      the oncologic and functional outcomes in patients with surgical history and large
      prostate volume.

PMID- 29633802
TI  - Bilateral synchronous testicular seminoma: A rare presentation of a rare disease.
AB  - OBJECTIVE: To present a case of a bilateral synchronous testicular seminoma in a
      young male clinical stage IIB. MATERIAL AND METHOD: A 37 years old man presented
      a bilateral testicular mass with elevated tumoral markers. Histology of frozen
      section revealed bilateral seminoma and bilateral radical orchiectomy was
      performed. RESULT: Enhanced chest and abdominopelvic staging CT scan revealed a
      lymphadenopathy of 30 mm within the inter-aortocava nodal chain (stage IIB).
      Patient received three cycles of BEP. Three months later 18F-FDG PET showed no
      evidence of hypermetabolic activity and serum tumoral markers were normal.
      CONCLUSION: Bilateral testicular germ cell tumors are a rare disease. Management
      of this tumors is controversial. Bilateral radical orchiectomy is the standard of
      care, nevertheless, in order to preserve fertility and androgen production, an
      organsparing surgery can be attempted in selected cases. Although prognosis is
      good, with overall survival rates similar to patients with unilateral disease,
      life-long close follow-up may be advocated due to relapse risk.

PMID- 29633803
TI  - Conservative management of a bladder leiomyosarcoma in a 43-year-old patient.
AB  - Leiomyosarcoma of the bladder is an aggressive and rare tumor, with less than 200
      reported cases. The treatment of bladder leiomyosarcoma is controversial although
      in most cases an aggressive surgical therapy is preferred. Usually, a radical
      cystectomy is performed, as it is considered to have a better disease-specific
      survival rate. A 43-year-old man presented to our Urology Department with
      painless macroscopic hematuria. He was submitted to transurethral resection of
      the tumor. The transurethral resection was complete and revealed only this small
      single lesion and the rest of the bladder was normal with no other lesion or
      suspicious lesion. The final histology revealed leiomyosarcoma of the bladder.
      Due to his age and the aggressiveness of the tumor after a thorough and detailed
      discussion with the patient a conservative management with aggressive follow up
      was decided. The patient a year after the diagnosis is in perfect condition
      without sign of a recurrence or metastastes.

PMID- 29633804
TI  - Metastasis of the epididymis and spermatic cord from pancreatic adenocarcinoma: A
      rare entity. Description of a case and revision of literature.
AB  - INTRODUCTION: Metastatic epididymal and spermatic cord adenocarcinoma from
      epithelial tumors are a rare condition. The most frequent primary cancers are
      prostate, lung, kidney, gastrointestinal tumors and breast. In literature, there
      are very low number of cases reporting metastasis from pancreatic cancer to
      epididymis and spermatic cord. CASE DESCRIPTION: We report a case of 70-years old
      man with history of left orchiectomy for undescended testicle, who presented to
      our department with a palpable nodule in the right scrotum. Scrotal ultrasound
      revealed an inhomogeneous hypoechoic nodule of epididymis and/or spermatic cord.
      Neoplastic markers showed high levels of CEA (carcinoembryonic antigen) and bHCG
      (beta Human Chorionic Gonadotropin). The patient underwent right surgical scrotal
      exploration with orchifunicolectomy. Pathologic examination revealed pathologic
      tissue showing rare glandular structures. Immunohistochemistry profile was
      compatible with malign epithelial neoplasm with glandular differentiation. Total
      body CT-scan revealed pathologic tissue in pancreas between head and body and a
      suspect pathologic lesion in liver and 18-FDG PET-scan confirmed the pancreatic
      neoplastic mass and a suspect secondary hepatic lesion. Biopsy of pancreatic
      pathologic area was positive for ductal pancreatic adenocarcinoma. The patient
      was sent to oncologic evaluation and started chemotherapy. CONCLUSIONS:
      Malignancies of epididymis and spermatic cord are rare entities and, in
      literature, very low number of cases of metastasis from pancreatic carcinoma to
      epididymis and spermatic cord are described. Early differential diagnosis is
      fundamental mostly in those patients with age range unusual for testis cancers.

PMID- 29633805
TI  - Pulmonary recurrence from prostate cancer and biochemical remission after
      metastasis directed therapy. A case report.
AB  - We report a case of a 69-years-old man who presented with a solitary 1 cm nodule
      in the lower lobe of the left lung almost 3 years after radical prostatectomy for
      pT3aN0M0, Gleason score 4+3 disease, without evidence of osseous or lymphatic
      spread. Surgical resection of the pulmonary lobe confirmed the metastatic nature
      of the lesion, with subsequent reduction of serum PSA to undetectable levels.
      After 2 years from the metastasis resection, serum PSA is still undetectable,
      without the necessity of additional treatments. Solitary pulmonary metastases
      from prostate cancer (Pca) are rare in clinical practice, with only 29 previous
      cases described besides the one that we present.

PMID- 29633806
TI  - Facile Fabrication of Large-Scale Silver Nanowire Bilayer Films and Its
      Application as Sensitive and Reproducible Surface-Enhanced Raman Scattering
      Substrates.
AB  - The homogeneous surface-enhanced Raman scattering (SERS) active hot spots on a
      SERS substrate is the most crucial factor in ensuring their application as
      reproducible and ultrasensitive sensing platforms. In this paper, we report on a
      simply shaking-assisted liquid-liquid (water-chloroform) interfacial assembly
      process for fabricating aligned Ag nanowire (AgNW) bilayer films on solid
      substrates. A scalable fabrication process can be easily realized by using a
      large size of container. These AgNW bilayer films can be used as ideal SERS
      active substrates for chemical and biomolecular detection with highly sensitivity
      and excellent reproducibility. Significantly, sensitive and quantitative
      detection of carbaryl with a detection limit of 0.1 ppm using these SERS
      substrates to demonstrate potential applications for environmental pollutant
      analysis.

PMID- 29633807
TI  - Phosphorus-Modified Palladium Hydrogenation Catalysts: An Electron-Microscopy
      Study.
AB  - Size and phase composition of the Pd-P catalyst, which is highly active in the
      hydrogenation of unsaturated compounds have been established using X-ray powder
      diffraction (XRD) analysis, high resolution transmission electron microscopy
      (HRTEM) technique in combination with energy-dispersive X-ray (EDX) analysis and
      selected area electron diffraction (SAED) analysis. The reduction of Pd(acac)2
      with hydrogen in the presence of white phosphorus (P/Pd = 0.3) in N,N
      dimethylformamide (DMF) at 80  degrees C results in formation of Pd-enriched
      polycrystalline nanoparticles with a predominant diameter of 5.7 nm (C(Pd) = 1
      mmol.L-1) and 5.1 nm (C( Pd) = 5 mmol . L-1). The polycrystallites consist of
      palladium phosphides (Pd5P2, Pd3P0.8 and palladium crystallites. It is found that
      phase composition of the Pd-P catalyst is changed at the stage of Pd-P sample
      preparation for XRD analysis. It is established that palladium phosphide Pd6P
      detected by XRD technique is a product of the solid-phase reaction between Pd
      crystallites and Pd5P2, Pd3P(0.8) palladium phosphides at the stage of high
      temperature sample preparation (400  degrees C). The mechanism of low-temperature
      synthesis of palladium phosphides was proposed.

PMID- 29633808
TI  - Synthesis of Silver Nanowire and Preparation of Uniform, Highly Conductive
      Transparent Films on Flexible Substrate with Extremely Excellent Film
      Performance.
AB  - Silver nanowires were successfully synthesized by the two-step injection polyol
      method. Reaction time and centrifugation speed are critical factors enabling high
      length and diameter ratio of silver nanowires. The effects of the two factors on
      the morphology of silver nanowires were investigated in the experiment of
      synthesis of silver nanowires, respectively. The optimal experimental conditions
      are that the reaction time is 1 hour and the centrifugal speed is 2000 rpm. The
      length and diameter of the prepared silver nanowires reaches 5-10 MUm and 60 nm,
      respectively. Silver nanowires were used for preparing transparent conductive
      film through vacuum filtration method, and then transferred to polyethylene
      glycol terephthalate (PET) substrate. The adhesive ability between the substrate
      and silver nanowire layer is greatly improved with spinning Polyvinylidene
      Fluoride (PVDF) on the silver nanowire network. Silver nanowire network on PET
      substrates showed an excellent stability, a good combination of high electrical
      conductivity and light transmittance. The transmittance of silver nanowires film
      reaches 71.5% and resistance is 65.5 ohm/sq. And the sheet resistance decreased
      significantly while the light transmittance had a little change when spun coated
      PVDF solutions on top of the silver nanowire film.

PMID- 29633809
TI  - Effluent Disinfection of Real Wastewater by Ag-TiO2 Nanoparticles Photocatalysis.
AB  - Currently pathogen microorganisms, presents in wastewater, are more resistant to
      conventional disinfection process, due to its constant change induced for the
      antibiotic for human diseases. One of the new options for the pathogen
      microorganisms is the heterogeneous photocatalysis, which has been used for
      remove microorganism, but never in real wastewater effluent. This paper shown the
      synthesis of Ag-TiO2 nanoparticles, its physical characterization was carried out
      by TEM, SEM, S-BET, XPS and band gap measurement by UV-vis spectroscopy showing
      that Ag-TiO2 are spherical particles with sizes around 50 nm with 1 and 10 %w of
      Ag, and a significant decrease in the band gap. The disinfection system was
      illuminated using the solar radiation of a spring day at Queretaro, Mexico, in
      lapses from 11:00 am to 03:00 pm; the microbiological tests were performed
      according to the Official Mexican Norm (NOM-003-SEMARNAT-1996), the results shows
      that after 3 hours of solar photocatalysis disinfection process the material 1 %w
      Ag-TiO2 at 0.2 gL-1, removes the fecal and total coliform microorganisms from
      effluent, leaving Enterobacter, Escherichia, Citrobacter, Salmonella and
      Klebsiella microorganisms alive due to its capability of reactivation.

PMID- 29633810
TI  - Nanostructured Bimetallic Iron Molybdenum Nitride as a Non-Precious Cathode
      Catalyst for Li-O2 Batteries.
AB  - Herein we report the facile fabrication and electrocatalytic activity of
      nanostructured bimetallic iron molybdenum nitride (Fe3Mo3N), which was prepared
      by an ammonolysis process directly towards the solid state mixture of Mo
      precursor and Fe precursor. The prepared nanostructured Fe3Mo3N presented
      remarkable electrocatalytic activities towards both oxygen reduction reaction and
      oxygen evolution reaction in nonaqueous phase, due to the modulation of
      electronic configuration of catalyst by Fe element and porous structure. Then,
      lithium-O2 batteries with nanostructured Fe3Mo3N as cathode catalysts were
      assembled, which show alleviated polarization and enhanced cyclability.

PMID- 29633811
TI  - Synthesis and Scanning Tunneling Microscopy Observation of 1,3,5-Triazine Bearing
      Azo-Carboxylate.
AB  - A new compound (2,4,6-tris-(3,5-di-methyl formate-4'-hydroxy azobenzene)-1,3,5
      triazine,TDHAT) has been synthesized and the scanning tunneling microscopy (STM)
      is utilized to clarify the geometrical configuration on the highly oriented
      pyrolytic graphite (HOPG) surface. The star-shaped molecule self-assembles into
      uniform and regular triangular petal structure at liquid-solid interface, and
      high-resolution images has been obtained, which implied a high stability of this
      two dimensional configuration. The distance between the scattered bright spot and
      the center of the petal is measured to be about 1.2 nm (L2), which corresponds to
      the actual size of each arm. Moreover, a comparison has been made between the
      TDHAT molecule and the TMA 4a molecule which has similar star-shaped structure
      with a long alkyl chain at the each end of the three arms, drawing a conclusion
      that both the structure of arms and the substituent groups would impact the
      nanoarchitecture. The results give us insight into a better comprehension of the
      self-assembly of the star-shaped molecule, which benefits the construction of
      functional nanostructures.

PMID- 29633812
TI  - A comparison of two different concentrations and infusion rates of ropivacaine in
      perineural infusion administered at the same total dose for analgesia after foot
      and ankle surgery: a randomized, double blinded, controlled study.
AB  - BACKGROUND: Continuous popliteal nerve block is utilized for postoperative
      analgesia after foot and ankle surgery. Whether only the total dose of local
      anesthetic or the combination of concentration and volume determine the
      characteristics of a continuous popliteal nerve infusion remains currently
      unknown. We hypothesized a reduction of the incidence of insensate extremity in
      patients given ropivacaine 0.4% at 4 mL/h compared to patients given ropivacaine
      0.2% at 8mL/h. METHODS: Sixty-four patients scheduled for major foot and ankle
      surgery requiring a continuous popliteal catheter infusion for postoperative
      analgesia were studied. Thirty-three patients were randomized to receive a
      continuous popliteal nerve block with 0.2% (basal 8 mL/h) and thirty-one with
      0.4% (basal 4 mL/h) ropivacaine, reaching the same total dose (16 mg/h). The
      primary outcome was the incidence of persistent sensory block in the distal
      sciatic nerve distributions in the postoperative period. Secondary outcomes were
      the incidence of motor block, NRS pain scores at rest in the postoperative period
      up to 48 hours after surgery, opioid use and related side effects, patients'
      satisfaction. RESULTS: The incidence of persistent sensory block was similar in
      patients given 0.2% and in patients receiving 0.4% ropivacaine. The incidence of
      motor block, postoperative pain scores at rest, use of oral opioids, side effects
      and patients' satisfaction with the quality of recovery were also similar in both
      groups. CONCLUSIONS: Our results suggest that local anesthetic total dose is the
      primary determinant of continuous popliteal perineural infusion effects.

PMID- 29633813
TI  - Effects of warmed, humidified CO2 insufflation on body core temperature and
      cytokine response: head-to-head randomized comparison vs. standard insufflation
      during RARP.

PMID- 29633814
TI  - Patient management after total knee arthroplasty: and the quest continues!

PMID- 29633815
TI  - Unconventional monitoring methods: can BIS(r) predict airway obstruction?

PMID- 29633816
TI  - Erector spinae plane block and dual antiplatelet therapy.

PMID- 29633817
TI  - Obstructive sleep apnea: screening is the waiting room for preoperative testing,
      postoperative monitoring, and safety measures.

PMID- 29633818
TI  - Patient-targeted light sedation in the Intensive Care Unit: are we ready for
      precision medicine with dexmedetomidine?

PMID- 29633819
TI  - In-Situ Preparation of Surface-Functionalized SiO2 Nanoparticles with
      Controllable Sizes.
AB  - Controllable preparation of small-sized SiO2 nanoparticles via sol-gel method
      remains a big challenge due to high reactivity of these nanoparticles. In this
      study, we demonstrated that when introducing coupling reagents, typically 3
      (methacryloxy)propyltrimethoxysilane during reaction, the growth of silica
      nanoparticles can be inhibited to a large degree and the diameters can be kept
      nearly constant. Further, the minimum diameter can be greatly reduced to around
      10 nm. DLS and SEM measurements indicated that the dispersion of the size of as
      prepared silica nanoparticles was narrow. No obvious aggregation was found in the
      absence of any stabilizing reagents. FT-IR results showed that the surface of the
      silica was functionalized with considerably large number of vinyl groups. Further
      grafting experiment demonstrated that the amount of vinyl groups was adequately
      large for the grafting of polymers to form core-shell structures. Overall, the
      coupling reagents served not only as surface modifier, but also as terminator of
      sol-gel reaction.

PMID- 29633820
TI  - Exploring patients' experiences with thyroid hormones' replacement therapy:
      gaining a better insight into drivers and barriers.

PMID- 29633821
TI  - One-Dimensional CoO@C Core-Shell Nanostructures for Improved Lithium Storage
      Properties.
AB  - Exploring conversion-type anode materials with large and stable lithium storage
      properties as well as good rate performance still remains a great challenge. This
      work presents one-dimensional core-shell CoO@C nanostructures as high-performance
      anode materials for lithium ion batteries. TEM measurements show that interior
      voids and carbon shell can be observed in the core-shell nanostructures.
      Electrochemical impedance spectroscopy reveals that the coated carbon layer can
      remarkably reduce the charge transfer resistance of the electrochemical
      conversion reaction. Endowed with the combined advantages mentioned above, the
      present sample exhibits good electrochemical properties when tested as anode
      materials, such as high and stable lithium storage properties (877.2 mAh g-1
      after 100 cycles at 100 mA g-1 and 661.5 mAh g-1 after 500 cycles at 1 A g-1),
      superior rate performance, and long cycling life (over 500 cycles at high current
      density of 1 A g-1). These good performances make it a promising candidate for
      high-performance anode materials.

PMID- 29633822
TI  - Synthesis of Bi2Te3 Nanotubes Using Te Nanotubes as a Template.
AB  - Bi2Te3 nanotubes are synthesized by a facile two-step hydrothermal method. Te
      nanotubes are prepared firstly and then used as a template to produce Bi2Te3
      nanotubes. The structure and morphology of the synthesized nanotubes are
      characterized by X-ray diffraction, field emission scanning electron microscope,
      and transmission electron microscope. The synthesized Bi2Te3 nanotubes are
      several microns in length and about 400 nm in diameter. The growth process is
      investigated in detail under different experimental conditions. The formation
      mechanism of Bi2Te3 nanotubes from the Te nanotube template is proposed and
      discussed. Electrical property of single Bi2Te3 nanotube is investigated. The
      synthesis of smooth Bi2Te3 nanotubes opens up the opportunities of investigating
      novel physical phenomena of topological insulators with two independent surfaces.

PMID- 29633823
TI  - Ionic Liquid-Assisted Synthesis and Catalytic Properties of AuPd Bimetallic
      Particles.
AB  - Ionic liquid-assisted synthesis of inorganic materials has been demonstrated to
      be an efficient synthesis route in the inorganic community. Here AuPd alloy
      particles are successfully synthesized with the assistance of the ionic liquid 1
      octyl-3-methylimidazolium chloride ([OMIM]Cl) at room temperature. The p
      nitrophenol reduction reaction using the synthesized metal particles as the
      catalysts indicates that the synthesized Au(1)Pd(1) particles exhibit the highest
      catalytic activity in comparison with the studied AuPd particles, the Au and the
      Pd particles. Therefore, the present synthesis route could be used as an
      efficient synthesis strategy for fabrication of metal alloy particles with
      interesting catalytic properties.

PMID- 29633824
TI  - Room-Temperature and Aqueous Solution-Processed Two-Dimensional TiS2 as an
      Electron Transport Layer for Highly Efficient and Stable Planar n-i-p Perovskite
      Solar Cells.
AB  - In this study, a room-temperature and aqueous solution-processed two-dimensional
      (2D) transition-metal dichalcogenide TiS2 was applied as an electron transport
      layer (ETL) in planar n-i-p perovskite solar cells (Pero-SCs). Upon insertion of
      the 2D TiS2 ETL with UV-ozone (UVO) treatment, the power conversion efficiency
      (PCE) of the planar Pero-SCs was optimized to 18.79%. To the best of our
      knowledge, this value should be the highest efficiency to date among those PCEs
      of the n-i-p Pero-SCs with room-temperature-processed metal compound ETLs. More
      importantly, the n-i-p Pero-SCs with the UVO-treated 2D TiS2 as an ETL also show
      extremely high stability, where the average PCE remained over 95% of its initial
      value after 816 h storage without encapsulation.

PMID- 29633825
TI  - Toward High-Performance and Low-Cost Hydrogen Evolution Reaction
      Electrocatalysts: Nanostructuring Cobalt Phosphide (CoP) Particles on Carbon
      Fiber Paper.
AB  - In this communication, we facily fabricated nanostructured CoP particles (150 to
      200 nm) on carbon fiber paper (CFP) for hydrogen evolution reaction (HER) by a
      simple two-step process via a green route. In the first step, crystalline Co3O4
      nanocubes (150-200 nm) were loaded on CFP through a hydrothermal process at low
      temperature (120  degrees C). Interestingly, crystalline Co3O4 nanocubes with a
      size 150-200 nm exhibited different growth mechanisms in contrast to the
      crystalline Co3O4 nanocubes with a size <100 nm reported earlier. In the second
      step, these crystalline Co3O4 nanocubes were converted to catalytically active
      CoP particles through chemical vapor deposition (CVD) phosphorization (denoted as
      CoP/CFP-H). Remarkably, CoP/CFP-H exhibited a low Tafel slope of 49.7 mV/dec and
      only required overpotentials of 128.1, 144.4, and 190.8 mV to drive geometric
      current densities of -10, -20, and -100 mA cm-2, respectively. Besides, the
      CoP/CFP-H also demonstrated an excellent durability in an acidic environment
      under 2000 sweeps at a high scan rate (100 mV s-1) and a 24 h chronopotentiometry
      testing. For comparison, CoP was also fabricated through the electrodeposition
      method, followed by CVD phosphorization (denoted as CoP/CFP-E). It was found that
      the latter had exhibited inferior activity compared to CoP/CFP-H. The good
      performances of CoP/CFP-H are essentially due to the rational designs of
      electrode: (i) the applications of highly HER active CoP electrocatalyst, (ii)
      the intimate contact of nanostructured CoP on carbon fibers, and (iii) the large
      electrochemical surface area at electrocatalyst/electrolyte interface due to the
      large retaining of particles features after phosphorization. Notably, the
      intermediate Co3O4/CFP can serve as a platform to develop other cobalt-based
      functional materials.

PMID- 29633826
TI  - Tunable Crystallization and Nucleation of Planar CH3NH3PbI3 through Solvent
      Modified Interdiffusion.
AB  - A smooth and compact light absorption perovskite layer is a highly desirable
      prerequisite for efficient planar perovskite solar cells. However, the rapid
      reaction between CH3NH3I methylammonium iodide (MAI) and PbI2 often leads to an
      inconsistent CH3NH3PbI3 crystal nucleation and growth rate along the film depth
      during the two-step sequential deposition process. Herein, a facile solvent
      additive strategy is reported to retard the crystallization kinetics of
      perovskite formation and accelerate the MAI diffusion across the PbI2 layer. It
      was found that the ultrasmooth perovskite thin film with narrow crystallite size
      variation can be achieved by introducing favorable solvent additives into the MAI
      solution. The effects of dimethylformamide, dimethyl sulfoxide, gamma
      butyrolactone, chlorobenzene, and diethyl ether additives on the morphological
      properties and cross-sectional crystallite size distribution were investigated
      using atomic force microscopy, X-ray diffraction, and scanning electron
      microscopy. Furthermore, the light absorption and band structure of the as
      prepared CH3NH3PbI3 films were investigated and correlated with the photovoltaic
      performance of the equivalent solar cell devices. Details of perovskite
      nucleation and crystal growth processes are presented, which opens new avenues
      for the fabrication of more efficient planar solar cell devices with these
      ultrasmooth perovskite layers.

PMID- 29633827
TI  - Gut Microbiota: Rational Manipulation of Gut Bacterial Metalloenzymes Provides
      Insights into Dysbiosis and Inflammation.

PMID- 29633828
TI  - Synergistic Effect of Charge Generation and Separation in Epitaxially Grown
      BiOCl/Bi2S3 Nano-Heterostructure.
AB  - Nano-heterostructures are widely used in the field of optoelectronic devices, and
      an optimal proportion usually exists between the constituents that make up the
      structures. Investigation on the mechanism underlying the optimal ratio is
      instructive for fabricating nano-heterostructures with high efficiency. In this
      work, BiOCl/Bi2S3 type-II nano-heterostructures with different Bi2S3/BiOCl ratios
      have been prepared via epitaxial growth of Bi2S3 nanorods on BiOCl nanosheets
      with solvothermal treatment at different sulfuration temperatures (110-180 
      degrees C) and their photoelectrochemical (PEC) performances as photoanodes have
      been studied. Results indicate that the Bi2S3 content increases with the
      sulfuration temperature. BiOCl/Bi2S3-170 (i.e., sulfurized@170  degrees C)
      exhibits the highest PEC performance under visible-light illumination, whereas
      BiOCl/Bi2S3-180 with the maximum Bi2S3 content shows the highest visible-light
      absorption, i.e., possessing the best potential for charge generation. Further
      analysis indicates that the BiOCl/Bi2S3 heterojunction interface is also crucial
      in determining the PEC performance of the obtained heterostructures by
      influencing the charge separation process. With increasing Bi2S3 content, the
      interface area in the BiOCl/Bi2S3 nano-heterostructures increases first and then
      decreases due to the mechanical fragility of the nanosheet-nanorod structure and
      the structural instability in the [010] direction of Bi2S3 with higher Bi2S3
      content. Therefore, the increasing content of the Bi2S3 does not necessarily
      correspond to higher heterojunction area. The optimal performance of BiOCl/Bi2S3
      170 results from the maximum of the synthetic coordination of the charge
      generation and separation. This is the first time ever to figure out the detailed
      explanation of the optimal property in the nano-heterostructures. The result is
      inspiring in designing high-performance nano-heterostructures from the point of
      synthesizing morphological mechanically robust heterostructure and structurally
      stable constituents to reach a high interfacial area, as well as high light
      absorption ability.

PMID- 29633829
TI  - Noncanonical Photodynamics of the Orange/Green Cyanobacteriochrome Power Sensor
      NpF2164g7 from the PtxD Phototaxis Regulator of Nostoc punctiforme.
AB  - Forward and reverse primary (<10 ns) and secondary (>10 ns) photodynamics of
      cyanobacteriochrome (CBCR) NpF2164g7 were characterized by global analysis of
      ultrafast broadband transient absorption measurements. NpF2164g7 is the most C
      terminal bilin-binding GAF domain in the Nostoc punctiforme phototaxis sensor
      PtxD (locus Npun_F2164). Although a member of the canonical red/green CBCR
      subfamily phylogenetically, NpF2164g7 exhibits an orange-absorbing 15ZPo dark
      adapted state instead of the typical red-absorbing 15ZPr dark-adapted state
      characteristic of this subfamily. The green-absorbing 15EPg photoproduct of
      NpF2164g7 is unstable, allowing this CBCR domain to function as a power sensor.
      Photoexcitation of the 15ZPo state triggers inhomogeneous excited-state dynamics
      with three spectrally and temporally distinguishable pathways to generate the
      light-adapted 15EPg state in high yield (estimated at 25-30%). Although observed
      in other CBCR domains, the inhomogeneity in NpF2164g7 extends far into secondary
      relaxation dynamics (10 ns -1 ms) through to formation of 15EPg. In the reverse
      direction, the primary dynamics after photoexcitation of 15EPg are qualitatively
      similar to those of other red/green CBCRs, but secondary dynamics involve a "pre
      equilibrium" step before regenerating 15ZPo. The anomalous photodynamics of
      NpF2164g7 may reflect an evolutionary adaptation of CBCR sensors that function as
      broadband light intensity sensors.

PMID- 29633830
TI  - Ceria Nanoparticles-Decorated Microcapsules as a Smart Drug Delivery/Protective
      System: Protection of Encapsulated P. pyralis Luciferase.
AB  - The design of novel, effective drug delivery systems is one of the most promising
      ways to improve the treatment of socially important diseases. This article
      reports on an innovative approach to the production of composite microcontainers
      (microcapsules) bearing advanced protective functions. Cerium oxide (CeO2)
      nanoparticles were incorporated into layer-by-layer polyelectrolyte microcapsules
      as a protective shell for an encapsulated enzyme (luciferase of Photinus
      pyralis), preventing its oxidation by hydrogen peroxide, the most abundant type
      of reactive oxygen species (ROS). The protective effect depends on CeO2 loading
      in the shell: at a low concentration, CeO2 nanoparticles only scavenge ROS,
      whereas a higher content leads to a decrease in access for both ROS and the
      substrate to the enzyme in the core. By varying the nanoparticle concentration in
      the microcapsule, it is possible to control the level of core shielding, from ROS
      filtering to complete blocking. A comprehensive analysis of microcapsules by
      transmission electron microscopy, scanning electron microscopy, atomic force
      microscopy, confocal laser scanning microscopy, and energy-dispersive X-ray
      spectroscopy techniques was carried out. Composite microcapsules decorated with
      CeO2 nanoparticles and encapsulated luciferase were shown to be easily taken up
      by rat B-50 neuronal cells; they are nontoxic and are able to protect cells from
      the oxidative stress induced by hydrogen peroxide. The approach demonstrated that
      the active protection of microencapsulated substances by CeO2 nanoparticles can
      be used in the development of new drug delivery and diagnostic systems.

PMID- 29633831
TI  - Protein Enables Conformation Transition of a Hydrogel Based on Pentapeptide and
      Boosts Immune Response in Vivo.
AB  - We report a supramolecular hydrogel based on dihistidine containing pentapeptides
      serving as a novel vaccine delivery system. Protein encapsulated into the
      hydrogel not only enhances the mechanical property up to 15-fold but also changes
      the conformation of the resulting nanostructure from a beta-sheet to an alpha
      helix. The resulting hybrid hydrogel enhances antigen uptake and moderately
      promotes dendritic cell (DC) maturation in vitro. More importantly, the
      pentapeptide hydrogel promotes antigen-specific antibody production in vivo and
      splenocyte proliferation ex vivo.

PMID- 29633832
TI  - Mechanical Forces Guiding Staphylococcus aureus Cellular Invasion.
AB  - Staphylococcus aureus can invade various types of mammalian cells, thereby
      enabling it to evade host immune defenses and antibiotics. The current model for
      cellular invasion involves the interaction between the bacterial cell surface
      located fibronectin (Fn)-binding proteins (FnBPA and FnBPB) and the alpha5beta1
      integrin in the host cell membrane. While it is believed that the extracellular
      matrix protein Fn serves as a bridging molecule between FnBPs and integrins, the
      fundamental forces involved are not known. Using single-cell and single-molecule
      experiments, we unravel the molecular forces guiding S. aureus cellular invasion,
      focusing on the prototypical three-component FnBPA-Fn-integrin interaction. We
      show that FnBPA mediates bacterial adhesion to soluble Fn via strong forces
      (~1500 pN), consistent with a high-affinity tandem beta-zipper, and that the
      FnBPA-Fn complex further binds to immobilized alpha5beta1 integrins with a
      strength much higher than that of the classical Fn-integrin bond (~100 pN). The
      high mechanical stability of the Fn bridge favors an invasion model in which Fn
      binding by FnBPA leads to the exposure of cryptic integrin-binding sites via
      allosteric activation, which in turn engage in a strong interaction with
      integrins. This activation mechanism emphasizes the importance of protein
      mechanobiology in regulating bacterial-host adhesion. We also find that Fn
      dependent adhesion between S. aureus and endothelial cells strengthens with time,
      suggesting that internalization occurs within a few minutes. Collectively, our
      results provide a molecular foundation for the ability of FnBPA to trigger host
      cell invasion by S. aureus and offer promising prospects for the development of
      therapeutic approaches against intracellular pathogens.

PMID- 29633833
TI  - Bacteria-Targeting Nanoparticles with Microenvironment-Responsive Antibiotic
      Release To Eliminate Intracellular Staphylococcus aureus and Associated
      Infection.
AB  - Staphylococcus aureus ( S. aureus) is a causative agent in life-threatening human
      diseases that afflict millions of people annually. Traditional antibiotic
      treatments are becoming less efficient because S. aureus can invade host cells
      including osteoblasts and macrophages, constituting a reservoir that is
      relatively protected from antibiotics that can lead to recrudescent infection. We
      herein report a unique intracellular antibiotic delivery nanoparticle, which is
      composed of (i) a mesoporous silica nanoparticle (MSN) core loaded with
      gentamicin, (ii) an infected microenvironment (bacterial toxin)-responsive lipid
      bilayer surface shell, and (iii) bacteria-targeting peptide ubiquicidin (UBI29
      41) that is immobilized on the lipid bilayer surface shell. The lipid material
      acts as a gate that prevents drug release before the MSNs reach the target cells
      or tissue, at which point they are degraded by bacterial toxins to rapidly
      release the drug, thus eliminating efficient bacteria. We confirm rapid drug
      release in the presence of bacteria in an extracellular model and observe that S.
      aureus growth is effectively inhibited both in vitro and in vivo of planktonic
      and intracellular infection. The inflammation-related gene expression in infected
      preosteoblast or macrophage is also downregulated significantly after treatment
      by the antibiotic delivery nanoparticles. The antibiotic delivery nanoparticles
      offer advantages in fighting intracellular pathogens and eliminating the
      inflammation caused by intracellular bacterial infections.

PMID- 29633834
TI  - Tuned Amperometric Detection of Reduced beta-Nicotinamide Adenine Dinucleotide by
      Allosteric Modulation of the Reductase Component of the p-Hydroxyphenylacetate
      Hydroxylase Immobilized within a Redox Polymer.
AB  - We report the fabrication of an amperometric NADH biosensor system that employs
      an allosterically modulated bacterial reductase in an adapted osmium(III)-complex
      modified redox polymer film for analyte quantification. Chains of complexed
      Os(III) centers along matrix polymer strings make electrical connection between
      the immobilized redox protein and a graphite electrode disc, transducing
      enzymatic oxidation of NADH into a biosensor current. Sustainable anodic
      signaling required (1) a redox polymer with a formal potential that matched the
      redox switch of the embedded reductase and avoided interfering redox interactions
      and (2) formation of a cross-linked enzyme/polymer film for stable biocatalyst
      entrapment. The activity of the chosen reductase is enhanced upon binding of an
      effector, i.e. p-hydroxy-phenylacetic acid ( p-HPA), allowing the acceleration of
      the substrate conversion rate on the sensor surface by in situ addition or
      preincubation with p-HPA. Acceleration of NADH oxidation amplified the response
      of the biosensor, with a 1.5-fold increase in the sensitivity of analyte
      detection, compared to operation without the allosteric modulator. Repetitive
      quantitative testing of solutions of known NADH concentration verified the
      performance in terms of reliability and analyte recovery. We herewith established
      the use of allosteric enzyme modulation and redox polymer-based enzyme electrode
      wiring for substrate biosensing, a concept that may be applicable to other
      allosteric enzymes.

PMID- 29633835
TI  - Reversible Carboxylate Shift in a MU-Oxo Diferric Complex in Solution by Acid
      /Base-Addition.
AB  - A reversible carboxylate shift has been observed in a MU-oxo diferric complex in
      solution by UV-vis-NIR and FTIR spectroscopy triggered by the addition of a base
      or an acid. A terminal acetate decoordinates upon the addition of a proton,
      resulting in a shift of the remaining terminal acetato to a MU-eta1:eta1 bridge.
      The addition of a base restores the original structure containing only terminal
      acetates. The implications for metalloenzymes with carboxylate-bridged nonheme
      diiron active sites are discussed.

PMID- 29633836
TI  - Multimodal Cleavable Reporters versus Conventional Labels for Optical
      Quantification of Accessible Amino and Carboxy Groups on Nano- and
      Microparticles.
AB  - Many applications of nanometer- and micrometer-sized particles include their
      surface functionalization with linkers, sensor molecules, and analyte recognition
      moieties like (bio)ligands. This requires knowledge of the chemical nature and
      number of surface groups accessible for subsequent coupling reactions.
      Particularly attractive for the quantification of these groups are
      spectrophotometric and fluorometric assays, which can be read out with simple
      instrumentation. In this respect, we present here a novel family of cleavable
      spectrophotometric and multimodal reporters for conjugatable amino and carboxyl
      surface groups on nano- and microparticles. This allows determination of particle
      bound labels, unbound reporters in the supernatant, and reporters cleaved off
      from the particle surface, as well as the remaining thiol groups on particle, by
      spectrophotometry and inductively coupled optical emission spectrometry (32S ICP
      OES). Comparison of the performance of these cleavable reporters with
      conductometry and conventional labels, utilizing changes in intensity or color of
      absorption or emission, underlines the analytical potential of this versatile
      concept which elegantly circumvents signal distortions by scattering and encoding
      dyes and enables straightforward validation by method comparison.

PMID- 29633837
TI  - Insight into Chemistry on Cloud/Aerosol Water Surfaces.
AB  - Cloud/aerosol water surfaces exert significant influence over atmospheric
      chemical processes. Atmospheric processes at the water surface are observed to
      follow mechanisms that are quite different from those in the gas phase. This
      Account summarizes our recent findings of new reaction pathways on the water
      surface. We have studied these surface reactions using Born-Oppenheimer molecular
      dynamics simulations. These studies provide useful information on the reaction
      time scale, the underlying mechanism of surface reactions, and the dynamic
      behavior of the product formed on the aqueous surface. According to these
      studies, the aerosol water surfaces confine the atmospheric species into a
      specific orientation depending on the hydrophilicity of atmospheric species or
      the hydrogen-bonding interactions between atmospheric species and interfacial
      water. As a result, atmospheric species are activated toward a particular
      reaction on the aerosol water surface. For example, the simplest Criegee
      intermediate (CH2OO) exhibits high reactivity toward the interfacial water and
      hydrogen sulfide, with the reaction times being a few picoseconds, 2-3 orders of
      magnitude faster than that in the gas phase. The presence of interfacial water
      molecules induces proton-transfer-based stepwise pathways for these reactions,
      which are not possible in the gas phase. The strong hydrophobicity of methyl
      substituents in larger Criegee intermediates (>C1), such as CH3CHOO and
      (CH3)2COO, blocks the formation of the necessary prereaction complexes for the
      Criegee-water reaction to occur at the water droplet surface, which lowers their
      proton-transfer ability and hampers the reaction. The aerosol water surface
      provides a solvent medium for acids (e.g., HNO3 and HCOOH) to participate in
      reactions via mechanisms that are different from those in the gas and bulk
      aqueous phases. For example, the anti-CH3CHOO-HNO3 reaction in the gas phase
      follows a direct reaction between anti-CH3CHOO and HNO3, whereas on a water
      surface, the HNO3-mediated stepwise hydration of anti-CH3CHOO is dominantly
      observed. The high surface/volume ratio of interfacial water molecules at the
      aerosol water surface can significantly lower the energy barriers for the proton
      transfer reactions in the atmosphere. Such catalysis by the aerosol water surface
      is shown to cause the barrier-less formation of ammonium bisulfate from hydrated
      NH3 and SO3 molecules rather than from the reaction of H2SO4 with NH3. Finally,
      an aerosol water droplet is a polar solvent, which would favorably interact with
      high polarity substrates. This can accelerate interconversion of different
      conformers (e.g., anti and syn) of atmospheric species, such as glyoxal,
      depending on their polarity. The results discussed here enable an improved
      understanding of atmospheric processes on the aerosol water surface.

PMID- 29633838
TI  - Control of the Speed of a Light-Induced Spin Transition through Mesoscale Core
      Shell Architecture.
AB  - The rate of the light-induced spin transition in a coordination polymer network
      solid dramatically increases when included as the core in mesoscale core-shell
      particles. A series of photomagnetic coordination polymer core-shell
      heterostructures, based on the light-switchable Rb aCo b[Fe(CN)6] c. mH2O (RbCoFe
      PBA) as core with the isostructural K jNi k[Cr(CN)6] l. nH2O (KNiCr-PBA) as
      shell, are studied using temperature-dependent powder X-ray diffraction and SQUID
      magnetometry. The core RbCoFe-PBA exhibits a charge transfer-induced spin
      transition (CTIST), which can be thermally and optically induced. When coupled to
      the shell, the rate of the optically induced transition from low spin to high
      spin increases. Isothermal relaxation from the optically induced high spin state
      of the core back to the low spin state and activation energies associated with
      the transition between these states were measured. The presence of a shell
      decreases the activation energy, which is associated with the elastic properties
      of the core. Numerical simulations using an electro-elastic model for the spin
      transition in core-shell particles supports the findings, demonstrating how
      coupling of the core to the shell changes the elastic properties of the system.
      The ability to tune the rate of optically induced magnetic and structural phase
      transitions through control of mesoscale architecture presents a new approach to
      the development of photoswitchable materials with tailored properties.

PMID- 29633839
TI  - Extracting the Americyl Hydration from an Americium Cationic Mixture in Solution:
      A Combined X-ray Absorption Spectroscopy and Molecular Dynamics Study.
AB  - Am(VI) solution chemistry differs from that of lighter actinoids, as U, Pu, and
      Np, where the actinyl [AnO2]2+ is the most stable form and plays an important
      role in nuclear fuel technology. The behavior of americium in solution shows the
      trend to stabilize lower oxidation states, mainly Am(III). Riddle and co-workers
      recently reported the EXAFS and first XANES spectra of an americium-containing
      aqueous solution where the americyl species is detected in a mixture. We have
      developed Am3+-H2O and [AmO2]2+-H2O intermolecular potentials based on quantum
      mechanical calculations to carry out classical MD simulations of these two
      cations in water. Structural information extracted from the statistical
      trajectories has been used to simulate EXAFS and XANES spectra of both solutions.
      For the Am3+ case the theoretical-experimental agreement for both EXAFS and XANES
      spectra is satisfactory. This is not the case for the [AmO2]2+ aqueous solutions.
      However, when an aqueous solution mixture of both cationic forms in a 55/45
      [AmO2]2+/Am3+ ratio is considered, the theoretical-experimental agreement is
      recovered. EXAFS and XANES spectra which would correspond to a pure [AmO2]2+
      aqueous solution are proposed. In the XANES case, the main features
      characterizing the simulated spectrum are consistent with those previously found
      in the experimental XANES spectra of stable [UO2]2+ and [PuO2]2+ in water.

PMID- 29633840
TI  - Quantum Chemical Calculation of p Kas of Environmentally Relevant Functional
      Groups: Carboxylic Acids, Amines, and Thiols in Aqueous Solution.
AB  - Developing accurate quantum chemical approaches for calculating p Kas is of broad
      interest. Useful accuracy can be obtained by using density functional theory
      (DFT) in combination with a polarizable continuum solvent model. However, some
      classes of molecules present problems for this approach, yielding errors greater
      than 5 p K units. Various methods have been developed to improve the accuracy of
      the combined strategy. These methods perform well but either do not generalize or
      introduce additional degrees of freedom, increasing the computational cost. The
      Solvation Model based on Density (SMD) has emerged as one of the most commonly
      used continuum solvent models. Nevertheless, for some classes of organic
      compounds, e.g., thiols, the p Kas calculated with the original SMD model show
      errors of 6-10 p K units, and we traced these errors to inaccuracies in the
      solvation free energies of the anions. To improve the accuracy of p Kas
      calculated with DFT and the SMD model, we developed a scaled solvent-accessible
      surface approach for constructing the solute-solvent boundary. By using a
      "direct" approach, in which all quantities are computed in the presence of the
      continuum solvent, the use of thermodynamic cycles is avoided. Furthermore, no
      explicit water molecules are required. Three benchmark data sets of
      experimentally measured p Ka values, including 28 carboxylic acids, 10 aliphatic
      amines, and 45 thiols, were used to assess the optimized SMD model, which we call
      SMD with a scaled solvent-accessible surface (SMDsSAS). Of the methods tested,
      the M06-2X density functional approximation, 6-31+G(d,p) basis set, and SMDsSAS
      solvent model provided the most accurate p Kas for each set, yielding mean
      unsigned errors of 0.9, 0.4, and 0.5 p K units, respectively, for carboxylic
      acids, aliphatic amines, and thiols. This approach is therefore useful for
      efficiently calculating the p Kas of environmentally relevant functional groups.

PMID- 29633841
TI  - A Ring Polymer Molecular Dynamics Approach to Study the Transition between
      Statistical and Direct Mechanisms in the H2 + H3+ -> H3+ + H2 Reaction.
AB  - Because of its fundamental importance in astrochemistry, the H2 + H3+ -> H3+ + H2
      reaction has been studied experimentally in a wide temperature range. Theoretical
      studies of the title reaction significantly lag primarily because of the
      challenges associated with the proper treatment of the zero-point energy (ZPE).
      As a result, all previous theoretical estimates for the ratio between a direct
      proton-hop and indirect exchange (via the H5+ complex) channels deviate from the
      experiment, in particular, at lower temperatures where the quantum effects
      dominate. In this work, the ring polymer molecular dynamics (RPMD) method is
      applied to study this reaction, providing very good agreement with the
      experiment. RPMD is immune to the shortcomings associated with the ZPE leakage
      and is able to describe the transition from direct to indirect mechanisms below
      room temperature. We argue that RPMD represents a useful tool for further studies
      of numerous ZPE-sensitive chemical reactions that are of high interest in
      astrochemistry.

PMID- 29633843
TI  - Six-Coordinate Nitrato Complexes of Iron Porphyrins with Trans S-Donor Ligands.
AB  - The reaction of dimethyl sulfide (DMS) and tetrahydrothiophene (THT) with thin,
      amorphous layers of the nitrato complexes Fe(Por)(eta2-O2NO) (Por = meso
      tetraphenylporphyrinato dianion or meso-tetra- p-tolylporphyrinato dianion) at
      low temperature leads to formation of the corresponding six-coordinate complexes
      Fe(Por)(L)(eta1-ONO2) (L = DMS, THT) as characterized by Fourier transform
      infrared and optical spectroscopy measurements. Adduct formation was accompanied
      by bidentate-to-monodentate linkage isomerization of the nitrato ligand, with the
      FeIII center remaining in a high-spin electronic state. These adducts are
      thermally unstable; warming to room temperature restores the initial Fe(Por)(eta2
      O2NO) species.

PMID- 29633844
TI  - Ionic Liquid Designed for PEDOT:PSS Conductivity Enhancement.
AB  - Poly-3,4-ethylenedioxythiophene:polystyrenesulfonate (PEDOT:PSS) is a water
      processable conducting polymer with promise for use in transparent flexible
      electrodes and thermoelectric devices, but its conductivity is not satisfactory.
      Its low conductivity is attributed to the formation of hydrophilic/insulating PSS
      outer layers encapsulating the conducting/hydrophobic p-doped PEDOT cores.
      Recently a significant conductivity enhancement has been achieved by adding ionic
      liquid (IL). It is believed that ion exchange between PEDOT:PSS and IL components
      helps PEDOT to decouple from PSS and to grow into large-scale conducting domains,
      but the exact mechanism is still under debate. Here we show through free energy
      calculations using density functional theory on a minimal model that the most
      efficient IL pairs are the least tightly bound ones with the lowest binding
      energies, which would lead to the most efficient ion exchange with PEDOT:PSS.
      This spontaneous ion exchange followed by nanophase segregation between PEDOT and
      PSS, with formation of a pi-stacked PEDOT aggregate decorated by IL anions, is
      also supported by molecular dynamics performed on larger PEDOT:PSS models in
      solution. We also show that the most efficient IL anions would sustain the
      highest amount of charge carriers uniformly distributed along the PEDOT backbone
      to further enhance the conductivity, providing that they remain in the PEDOT
      domain after the ion exchange. Hence, our design principle is that the high
      performance IL should induce not only an efficient ion exchange with PEDOT:PSS to
      improve the PEDOT morphology (to increase mobility) but also a uniform high-level
      p-doping of PEDOT (to enhance intrinsic conductivity). Based on this principle, a
      promising (electron-withdrawing, but bulky, soft, and hydrophobic) new IL pair is
      proposed.

PMID- 29633842
TI  - Investigation of Substrate Recognition and Biosynthesis in Class IV Lanthipeptide
      Systems.
AB  - Lanthipeptides belong to the family of ribosomally synthesized and post
      translationally modified peptides (RiPPs) and are subdivided into four classes.
      The first two classes have been heavily studied, but less is known about classes
      III and IV. The lanthipeptide synthetases of classes III and IV share a similar
      organization of protein domains: A lyase domain at the N-terminus, a central
      kinase domain, and a C-terminal cyclase domain. Here, we provide deeper insight
      into class IV enzymes (LanLs). A series of putative producer strains was screened
      to identify production conditions of four new venezuelin-like lanthipeptides, and
      an Escherichia coli based heterologous production system was established for a
      fifth. The latter not only allowed production of fully modified core peptide but
      was also employed as the basis for mutational analysis of the precursor peptide
      to identify regions important for enzyme recognition. These experiments were
      complemented by in vitro binding studies aimed at identifying the region of the
      leader peptide recognized by the LanL enzymes as well as determining which domain
      of the enzyme is recognizing the substrate peptide. Combined, these studies
      revealed that the kinase domain is mediating the interaction with the precursor
      peptide and that a putatively alpha-helical stretch of residues at the center to
      N-terminal region of the leader peptide is important for enzyme recognition. In
      addition, a combination of in vitro assays and tandem mass spectrometry was used
      to elucidate the order of dehydration events in these systems.

PMID- 29633845
TI  - A Lanthanum Carboxylate Framework with Exceptional Stability and Highly Selective
      Adsorption of Gas and Liquid.
AB  - The development of porous metal-organic frameworks that can retain structural
      integrity under harsh physical and chemical conditions is essential from the
      perspective of their use in adsorption, catalysis, and sensors. Herein, a
      lanthanum carboxylate framework was found to exhibit exceptional stability, not
      only robust in boiling aqueous solutions at pH 2-12 and in boiling common organic
      solvents over 24 h but also stable upon ball milling for 1 h. Furthermore, this
      framework displayed highly selective separation for CO2 over N2 ( Sads = 940), as
      well as size-dependent selective adsorption behavior of water and alcohols.

PMID- 29633846
TI  - Studies toward the Synthesis of Iriomoteolide-2a: Construction of the C(6)-C(28)
      Fragment.
AB  - The synthesis of an appropriately functionalized advanced C(6-28) fragment (3) of
      the marine macrolide iriomoteolide-2a (1) has been achieved in a highly efficient
      manner. The C(6)-C(18) fragment of 1 is prepared via a radical cyclization of a
      vinyl ether intermediate and palladium-promoted hydrostannylation/iodination.
      Paterson aldol reaction and Peterson olefination are used to construct the C(19)
      C(28) fragment. The union of the C(6)-C(18) and C(19)-C(28) fragments is
      accomplished via a Suzuki-Miyaura coupling reaction.

PMID- 29633847
TI  - Direct Synthesis of 2-Methylbenzofurans from Calcium Carbide and Salicylaldehyde
      p-Tosylhydrazones.
AB  - A new methodology for the construction of methyl-substituted benzofuran rings
      from the reactions of calcium carbide with salicylaldehyde p-tosylhydrazones/2
      hydroxyacetophenone p-tosylhydrazones is described. Various 2-methylbenzofurans
      and 2,3-dimethylbenzofurans could be obtained in satisfactory yield by using a
      cuprous chloride catalyst. The advantages of this protocol include the use of a
      readily available and easy-to-handle acetylene source and simple workup
      procedure.

PMID- 29633848
TI  - Maximum Spreading and Rebound of a Droplet Impacting onto a Spherical Surface at
      Low Weber Numbers.
AB  - The spreading and rebound patterns of low-viscous droplets upon impacting
      spherical solid surfaces are investigated numerically. The studied cases consider
      a droplet impinging onto hydrophobic and superhydrophobic surfaces with various
      parameters varied throughout the study, and their effects on the postimpingement
      behavior are discussed. These parameters include impact Weber number (through
      varying the surface tension and impingement velocity), the size ratio of the
      droplet to the solid surface, and the surface contact angle. According to the
      findings, the maximum spreading diameter increases with the impact velocity, with
      an increase of the sphere diameter, with a lower surface wettability, and with a
      lower surface tension. Typical outcomes of the impact include (1) complete
      rebound, (2) splash, and (3) a final deposition stage after a series of spreading
      and recoiling phases. Finally, a novel, practical model is proposed, which can
      reasonably predict the maximum deformation of low Reynolds number impact of
      droplets onto hydrophobic or superhydrophobic spherical solid surfaces.

PMID- 29633849
TI  - Reconfigurable Vanadium Dioxide Nanomembranes and Microtubes with Controllable
      Phase Transition Temperatures.
AB  - Two additional structural forms, free-standing nanomembranes and microtubes, are
      reported and added to the vanadium dioxide (VO2) material family. Free-standing
      VO2 nanomembranes were fabricated by precisely thinning as-grown VO2 thin films
      and etching away the sacrificial layer underneath. VO2 microtubes with a range of
      controllable diameters were rolled-up from the VO2 nanomembranes. When a VO2
      nanomembrane is rolled-up into a microtubular structure, a significant
      compressive strain is generated and accommodated therein, which decreases the
      phase transition temperature of the VO2 material. The magnitude of the
      compressive strain is determined by the curvature of the VO2 microtube, which can
      be rationally and accurately designed by controlling the tube diameter during the
      rolling-up fabrication process. The VO2 microtube rolling-up process presents a
      novel way to controllably tune the phase transition temperature of VO2 materials
      over a wide range toward practical applications. Furthermore, the rolling-up
      process is reversible. A VO2 microtube can be transformed back into a
      nanomembrane by introducing an external strain. Because of its tunable phase
      transition temperature and reversible shape transformation, the VO2 nanomembrane
      microtube structure is promising for device applications. As an example
      application, a tubular microactuator device with low driving energy but large
      displacement is demonstrated at various triggering temperatures.

PMID- 29633850
TI  - Medical approaches to suffering are limited, so why critique Improving Access to
      Psychological Therapies from the same ideology.
AB  - Although the article by Scott rightly questions the dynamics of the Improving
      Access to Psychological Therapies system and re-examines the recovery rates,
      finding quite shocking results, his recommendations are ultimately flawed. There
      is a strong critique of the diagnostic procedures in Improving Access to
      Psychological Therapies services, but the answer is not to diagnose more
      rigorously and to adhere more strictly to a manualised approach to psychotherapy.
      The opposite may be required. Alternatives to the medical model of distress offer
      a less stigmatising and more human approach to helping people with their
      problems. Perhaps psychological therapists and the people they work alongside
      would be better served by a psychological approach rather than a psychiatric one.

PMID- 29633851
TI  - Internal extractive electrospray ionization-mass spectrometry: a powerful
      platform for bioanalysis.

PMID- 29633853
TI  - The prevalence of autistic traits in a homeless population.
AB  - Anecdotal evidence suggests that autistic people experience an elevated risk of
      homelessness, but systematic empirical research on this topic is lacking. As a
      step towards filling this gap in knowledge, we conducted a preliminary
      investigation of the prevalence of Diagnostic and Statistical Manual of Mental
      Disorders (5th ed.) autism symptoms in a group of long-term homeless people. The
      entire caseload ( N = 106) of a UK homeless outreach team was screened (excluding
      individuals born outside of the United Kingdom or Republic of Ireland) using an
      in-depth, semi-structured interview with keyworkers, based on Diagnostic and
      Statistical Manual of Mental Disorders (5th ed.) diagnostic criteria. This showed
      adequate inter-rater reliability, as well as evidence of criterion and construct
      validity. Of the sample, 13 people (12.3%, 95% confidence interval (7.0, 20.4))
      screened positive, meeting Diagnostic and Statistical Manual of Mental Disorders
      (5th ed.) autism criteria by keyworker report. A further nine people (8.5%, 95%
      confidence interval (4.5, 15.3)) were 'marginal', having autistic traits that
      were not quite sufficient to meet Diagnostic and Statistical Manual of Mental
      Disorders (5th ed.) criteria. Those with elevated autistic traits, compared to
      those without, tended to be more socially isolated and less likely to use
      substances. This study has provided initial evidence that autistic traits are
      over-represented among homeless people and that autistic homeless people may show
      a distinct pattern of characteristics and needs. Further investigation is
      required to build upon these provisional findings.

PMID- 29633852
TI  - Implementing systems-based innovations to improve access to early screening,
      diagnosis, and treatment services for children with autism spectrum disorder: An
      Autism Spectrum Disorder Pediatric, Early Detection, Engagement, and Services
      network study.
AB  - In 2013, the National Institute of Mental Health funded five trials of unique,
      multicomponent, systems-based innovations designed to improve access to early
      screening, diagnosis, and treatment of autism spectrum disorder-collectively
      known as the Autism Spectrum Disorder Pediatric, Early Detection, Engagement, and
      Services Network. As part of an ongoing effort to pool data and learn from shared
      experience, we collected information across all studies about innovation
      components and implementation strategies. First, each study group completed
      standardized checklists based on the Template for Intervention Description and
      Replication and the Expert Recommendation for Implementing Change. Then, we
      interviewed principal and co-investigators of each study (n = 9) to further
      explore innovation components and assess barriers and facilitators to
      implementation. Innovation strategies were diverse (five different autism
      spectrum disorder screeners were used, 40% included early intervention trainings,
      60% involved new technology). Common implementation strategies included
      developing stakeholder relationships and provider trainings. Barriers included
      inefficient systems of care, difficulty engaging families in the innovations,
      provider attitudes, and organizational culture (e.g. difficulty changing clinic
      processes). These findings suggest that-despite diverse settings and a variety of
      innovation content-common facilitators and challenges exist in implementing
      innovations to enhance access to early autism spectrum disorder screening,
      diagnosis, and treatment.

PMID- 29633854
TI  - Validated UHPLC-MS/MS method for quantification of doxycycline in abdominal
      aortic aneurysm patients.
AB  - AIM: There is a strong evidence that doxycycline can benefit abdominal aortic
      aneurysms patients because of its ability to inhibit matrix metalloproteinase
      enzymes. There is a need for a specific quantification method for doxycycline in
      these patients. We report herein the development and validation of a selective,
      specific, simple and rapid UHPLC-MS/MS method for doxycycline. RESULTS: The assay
      was linear (r2 > 0.994) over a concentration range of 0.010-7.005 MUg/ml. This
      validated method has good lower limit of quantification (LLOQ) (10 ng/ml),
      accuracies (89.1-103.4%), precision (<=7.0%) and extraction recoveries (95.8%).
      Doxycycline was stable during short- and long-term storage. CONCLUSION: The assay
      is reliable and has been successfully applied to serum samples obtained from the
      patients of N-TA3CT clinical study.

PMID- 29633855
TI  - A novel role of HIF-1alpha/PROX-1/LYVE-1 axis on tissue regeneration after renal
      ischaemia/reperfusion in mice.
AB  - CONTEXT: Renal ischaemia reperfusion (I/R) is a common clinical condition with a
      high morbidity and mortality rate. To date, I/R-induced renal injury remains an
      ineffective treatment. OBJECTIVE: We hypothesis that angiogenesis and
      lymphangiogenesis markers, prospero homeobox-1 (PROX-1) and lymphatic endothelial
      hyaluronan receptor-1 (LYVE-1), are critical during I/R. MATERIAL AND METHODS:
      Kunming mice were subjected to I/R and observed for the following eight
      consecutive days. Pathology analysis and protein distribution were detected by
      H&E staining, immunohistochemistry and immunofluorescence confocal analysis.
      RESULTS: After I/R treatment, renal pathology was changed. HIF-1alpha was induced
      in the early stage and colocalisation with PROX-1 mainly in the renal tubular
      region, whereas PROX-1 and LYVE-1 were colocalised in the glomerulus of the
      endothelial region. CONCLUSIONS: In this study, we revealed HIF-1alpha/PROX
      1/LVYE-1 axis dynamic changes in different regions after I/R and demonstrated for
      the first time it activates during I/R repair.

PMID- 29633856
TI  - Reduction of Environmental Listeria Using Gaseous Ozone in a Cheese Processing
      Facility.
AB  - A cheese processing facility seeking to reduce environmental Listeria
      colonization initiated a regime of ozonation across all production areas as an
      adjunct to its sanitation regimes. A total of 360 environmental samples from the
      facility were tested for Listeria over a 12-month period. A total of 15 areas
      before and 15 areas after ozonation were tested. Listeria isolations were
      significantly ( P < 0.001) reduced from 15.0% in the preozonation samples to
      1.67% in the postozonation samples in all areas. No deleterious effects of
      ozonation were noted on the wall paneling, seals, synthetic floors, or cheese
      processing equipment. The ozonation regime was readily incorporated by sanitation
      staff into the existing good manufacturing practice program. The application of
      ozone may result in a significant reduction in the prevalence of Listeria in food
      processing facilities.

PMID- 29633857
TI  - Smartphone-Based Self-Management of Non-Insulin-Dependent Diabetes: A Japanese
      System at Use by an Italian Patients' Cohort.

PMID- 29633858
TI  - US Army Soldiers With Type 1 Diabetes Mellitus.
AB  - US Army soldiers diagnosed with type 1 diabetes were previously considered unfit
      for duty. For highly motivated soldiers, current advanced technologies allow the
      possibility of not only retention on active duty, but military deployment. We
      present our experience at Fort Bragg, North Carolina, taking care of soldiers
      newly diagnosed with type 1 diabetes mellitus. Through intensive diabetes
      education, extensive military and physical training, optimization of diabetes
      technology, and remote real-time monitoring, soldiers are able to continue to
      serve their country in the most specialized roles.

PMID- 29633859
TI  - Conjugated linoleic acid enriched skim milk prepared with Lactobacillus fermentum
      DDHI27 endorsed antiobesity in mice.
AB  - AIM: This study evaluated the antiobesity effect of skim milk prepared with
      conjugated linoleic acid producing probiotic Lactobacillus fermentum DDHI27
      (PCLA). MATERIALS & METHODS: C57BL/6 J mice were divided into five groups, and
      different obesity-associated parameters were studied. RESULTS: PCLA
      supplementation alleviated body weight, epididymal and mesenteric fats and
      improves lipid profiles. Significant ameliorations in leptin, blood glucose,
      hepatic steatosis and reduction in adipocytes size were also observed.
      Additionally, feeding also led to positive alterations in the adipogenesis
      transcription factors and key lipogenesis genes. Improvement in the gut
      microbiota dysbiosis was also revealed. CONCLUSION: Results inferred that PCLA
      exerted an antiobesity effect in diet-induced obese mice and may be further
      developed in the functional foods for the management of obesity.

PMID- 29633860
TI  - Proposal for risk-based scientific approach on full and partial validation for
      general changes in bioanalytical method.
AB  - The guidance and several guidelines on bioanalytical method validation, which
      were issued by the US FDA, EMA and Ministry of Health, Labour and Welfare, list
      the 'full' validation parameters; however, none of these provide any details for
      'partial' validation. Japan Bioanalysis Forum approved a total of three annual
      discussion groups from 2012 to 2014. In the discussion groups, members from
      pharmaceutical companies and contract research organizations discussed the
      details of partial validation from a risk assessment viewpoint based on surveys
      focusing on bioanalysis of small molecules using LC-MS/MS in Japan. This
      manuscript presents perspectives and recommendations for most conceivable changes
      that can be made to full and partial validations by members of the discussion
      groups based on their experiences and discussions at the Japan Bioanalysis Forum
      Symposium.

PMID- 29633861
TI  - Approaches to measure protein binding of enzymatically unstable compounds in
      plasma.
AB  - AIM: To develop approaches to measure plasma protein binding (PPB) of
      enzymatically unstable compounds. METHODOLOGY: Bis-para-nitrophenyl phosphate
      (BNPP) was used to inhibit enzyme activity and stabilize two model compounds
      (diltiazem and oseltamivir) that are subject to enzyme-catalyzed hydrolysis in
      plasma. Protein binding of the compounds in BNPP-treated rat plasma was measured
      using equilibrium dialysis or ultrafiltration. CONCLUSION: PPB measurement of
      unstable compounds was improved by using enzyme inhibitor to stabilize the
      compounds in plasma during the assay. The effect of BNPP concentration on drug
      protein binding appeared to be compound dependent. Given the compound's
      nonspecific binding to the assay device can be accounted for in the unbound
      fraction measurement, ultrafiltration can be a viable alternative or
      complementary approach for PPB assay of unstable compounds while minimizing the
      potential impact of enzyme inhibitor on drug-protein binding.

PMID- 29633862
TI  - Validated HPLC-UV detection method for the simultaneous determination of
      ceftolozane and tazobactam in human plasma.
AB  - AIM: A simple, rapid, economical and sensitive HPLC-UV method was developed for
      the simultaneous quantification of ceftolozane and tazobactam in plasma samples.
      METHODOLOGY: After deproteinization followed by a liquid-liquid back-extraction,
      the compounds were separated on a C18 column (150 mm * 4.6 mm, 5 MUm) with UV
      visible detection at 220 nm. The mobile phase consisted of acetonitrile and
      potassium dihydrogenphosphate buffer at pH 3.0 (8:92, v/v), delivered
      isocratically at a flow rate of 1.0 ml/min and at a column oven temperature of 30
      degrees C. Cefepime was used as an internal standard. RESULTS: Linearity was
      achieved in the concentration range of 0.50-100.00 MUg/ml for ceftolozane and
      0.25-50.00 MUg/ml for tazobactam. The intra- and interday precision showed good
      reproducibility with coefficients of variation of less than 9.26% for ceftolozane
      and 9.62% for tazobactam. CONCLUSION: The sample preparation procedure avoids
      expensive or time-consuming steps used by other previously published methods. The
      methodology was validated according to standard guidelines and was used for
      quantification of ceftolozane and tazobactam in plasma samples from critically
      ill patients.

PMID- 29633863
TI  - Developing novel methods for protein, peptide and metabolite analysis.
AB  - Rainer Bischoff, Professor of Analytical Biochemistry at the University of
      Groningen (Groningen, The Netherlands), talks to Sankeetha Nadarajah, Managing
      Commissioning Editor (Bioanalysis), regarding the development of novel methods
      for protein, peptide and metabolite analysis.

PMID- 29633864
TI  - Common drug-drug interactions in antifungal treatments for superficial fungal
      infections.
AB  - INTRODUCTION: Antifungal agents can be co-administered alongside several other
      medications for a variety of reasons such as the presence of comorbidities.
      Pharmacodynamic interactions such as synergistic and antagonistic interactions
      could be the result of co-administered medications. Pharmacokinetic interactions
      could also transpire through the inhibition of metabolizing enzymes and drug
      transport systems, altering the absorption, metabolism and excretion of co
      administered medications. Both pharmacodynamic and pharmacokinetic interactions
      can result in hospitalization due to serious adverse effects associated with
      antifungal agents, lower therapeutic doses required to achieve desired antifungal
      activity, and prevent antifungal resistance. Areas covered: The objective of this
      review is to summarize pharmacodynamic and pharmacokinetic interactions
      associated with common antifungal agents used to treat superficial fungal
      infections. Pharmacodynamic and pharmacokinetic interactions that impact the
      therapeutic effects of antifungal agents and drugs that are influenced by the
      presence of antifungal agents was the context to which these antifungal agents
      were addressed. Expert opinion: The potential for drug-drug interactions is
      minimal for topical antifungals as opposed to oral antifungals as they have
      minimal exposure to other co-administered medications. Developing non-lipophilic
      antifungals that have unique metabolizing pathways and are topical applied are
      suggested properties that could help limit drug-drug interactions associated with
      future treatments.

PMID- 29633865
TI  - Uptake of rheumatology biosimilars in the absence of forced switching.
AB  - BACKGROUND: To describe the uptake and system-level effects of the introduction
      of biosimilars in a setting without forced switching. RESEARCH DESIGN AND
      METHODS: We used data from the Swedish Rheumatology Quality register from start
      of marketing of infliximab (Remsima(r) and Inflectra(r)) and etanercept
      (Benepali(r)) biosimilars until 31 December 2016. We compared users of each
      originator-product and its biosimilar(s) by line of treatment: bDMARD-naive
      patients, non-medical switchers (vs. matched patients remaining on originator),
      and patients switching from a previous bDMARD of another type. RESULTS: From the
      start of marketing 1343 patients started an infliximab biosimilar (22 months) and
      2691 started etanercept (9 months). Overall, the introduction of these
      biosimilars resulted in an increase of the total number of ongoing infliximab and
      etanercept treatments (originator + biosimilar) . At the end of the study period,
      biosimilars accounted for 31% of all infliximab treatments and 31% of all
      etanercept-treated patients. For each line of therapy, we noted only small
      differences in patient characteristics between those starting the originator
      product vs. its biosimilar(s). CONCLUSIONS: Introduction of biosimilars have
      effects beyond replacement of the originator product, in terms of an increased
      rate of bDMARD initiation. Selection to non-medical switching displayed no
      particular disease- or patient-characteristics.

PMID- 29633866
TI  - Triangular gold nanoparticles modify shell characteristics and increase
      antioxidant enzyme activities in the clam Ruditapes decussatus.
AB  - CONTEXT: Nanoparticles may cause adverse environmental effects but there is
      limited information on their interactions with marine organisms. OBJECTIVE: Our
      aim was to examine the effects of triangular gold nanoparticles (Tr-Au NPs) on
      the clam, Ruditapes decussatus. MATERIALS AND METHODS: Clams were exposed to Tr
      Au1 = 5 ug/L and Tr-Au2 = 10 ug/L for 2 and 7 days. Effects on shell structure
      were investigated. Superoxide dismutase (SOD), catalase (CAT), glutathione
      transferase (GST) activities, protein carbonyl levels and malondialdehyde content
      were used to assess biochemical status. RESULTS: Transmission electron microscopy
      (TEM) and electron dispersive X-ray microanalysis (EDX) showed that Tr-Au NPs
      modified shell structure and morphology. Tr-Au NPs size increased forming
      aggregate particles. Tr-Au NPs increased SOD, CAT and GST activities in gill and
      digestive gland in a concentration- and time-dependent manner indicating defence
      against oxidative stress. Enhanced lipid peroxidation and protein carbonyl levels
      confirmed oxidative stress. CONCLUSION: Tr-Au NPs cause oxidative stress and
      affect shell structure of clams. These findings may have relevance to other
      marine species.

PMID- 29633867
TI  - An update on adverse drug reactions related to beta-lactam antibiotics.
AB  - INTRODUCTION: beta-lactams have been consistently associated with the majority of
      drug-related adverse events. Generally, these are mild under proper dosing and
      judicious selection. Areas covered: Immediate hypersensitivity reactions are the
      most feared adverse events encountered after beta-lactam administration. Emerging
      evidence shows that immediate reactions are not as common as previously thought.
      Specialist consultation and testing seems prudent before a patient is officially
      declared allergic to beta-lactams. The risk of cross-reactions between not only
      members of the beta-lactam super-family but also between specific classes is also
      lower than previously thought. Newer studies have shown that cross-reactions are
      not universal and pertain to specific agents with similar side chains or
      metabolites of the beta-lactam core. The frequency of severe kidney or liver
      toxicity, neurotoxicity, cytopenias and Clostiridium difficile infection
      following beta-lactam administration seem to be agent-specific. Expert opinion:
      The currently available data denote that in addition to age, gender, co
      morbidity, renal or liver function, and co-administered agents, the antibiotic
      levels rather than the dose itself seem to be associated with the emergence of
      adverse events. Most of them subside with time after withdrawal of the offending
      agent, but the number of cases resulting in chronic disabilities or even deaths
      in not negligible.

PMID- 29633868
TI  - Topically applied 1% voriconazole induces dysplastic changes on the ocular
      surface: animal study.
AB  - PURPOSE: To identify the risk of inducing ocular surface dysplasia following
      topical administration of 1% voriconazole eye drop. METHODS: Fourteen noninflamed
      healthy eyes of 14 white adult New Zealand rabbits were included in the study.
      The rabbits were randomly divided into two groups comprised of 7 rabbits each.
      Group 1 received topical 1% voriconazole and Group 2 received topical saline as
      the control group. In all animals, right eye was selected for the study. In Group
      1 (Voriconazole Group), single drop of voriconazole was instilled every 10 min
      consecutively for 17 times a day for 60 days. In Group 2 (Control Group), single
      drop of saline was instilled every 10 min consecutively for 17 times a day for 60
      days. At two months, animals were sacrificed and study eyes were enucleated with
      the eyelids. The specimens were stained with hematoxylin-eosin and
      histopathologic changes in cornea, bulbar and palpebral conjunctiva were
      evaluated under light microscope. RESULTS: There were no macroscopically visible
      lesions on the ocular surface of any rabbits. Histopathological evaluation showed
      mild to moderate dysplasia localized mainly in the limbus and extending to the
      adjacent cornea and bulbar conjunctiva in all rabbits in Voriconazole Group.
      Severe dysplasia or carcinoma in situ was not observed. In the Control Group,
      dysplasia was not observed, at all. CONCLUSION: This animal study provides a
      possible relationship between topically administered 1% voriconazole and ocular
      surface dysplasia. We recommend ophthalmologists to be aware of the risk of
      ocular surface dysplasia in patients received voriconazole eye drop.

PMID- 29633869
TI  - Cabotegravir in the treatment and prevention of Human Immunodeficiency Virus-1.
AB  - INTRODUCTION: Human Immunodeficiency Virus (HIV) is a chronic infection that
      depletes the immune system of essential components causing those infected to be
      at risk for multiple life-threatening infections. Worldwide, millions live with
      this infection, the vast majority attributable to HIV-1. Transmission persists
      with hundreds of thousands of new infections reported yearly. Implementation of
      combination antiretroviral therapy (cART) has been effective in improving
      outcomes and decreasing transmission. Newer co-formulated agents have provided
      simpler medication regimens, fewer side effects, and, in some cases, a higher
      barrier to the emergence of medication resistance. Areas covered: Here, we review
      trials of cabotegravir (CAB) as treatment of HIV-1 infection and its potential
      use as pre-exposure prophylaxis (PrEP) in high risk individuals, including issues
      around oral lead in and potential resistance emergence. Expert opinion: CAB is
      efficacious when used in combination therapy orally or given intramuscularly
      every 4 to 8 weeks. Its availability in a long-acting injectable formulation (CAB
      LA) makes it a valuable, novel drug to treat HIV-1 infection when combined with
      long-acting injectable rilpivirine (RPV-LA). Moreover, pre-clinical and early
      Phase 2a studies support its testing as monotherapy as PrEP. Studies are underway
      comparing the efficacy of every 8 week CAB-LA to tenofovir disoproxil
      fumarate/emtricitabine (TDF/FTC).

PMID- 29633871
TI  - Timely intervention can reduce the cost of falls.

PMID- 29633870
TI  - Designing and implementing a trust-wide quality assurance programme.
AB  - Derbyshire Community Health Services (DCHS) NHS Foundation Trust provides a wide
      range of community-based health services. After the Care Quality Commission (CQC)
      found gaps in the trust's assurance process, its board decided to develop a
      method of continuous quality improvements that could be used as a basis for the
      trust's quality assurance system. The trust adapted and built on an acute model
      so it was suitable for community services. The final assurance system, Quality
      Always, has four elements: the clinical assessment and accreditation scheme;
      leadership development; 'champions' within clinical teams to support and promote
      the scheme; and dashboards to record and monitor progress. A system to recognise
      and reward achievement was essential for success. Quality Always has resulted in
      better care quality, an improved CQC rating, a sense of achievement among staff,
      the development of support networks, learning (especially among support staff)
      and good practice being shared.

PMID- 29633872
TI  - Focusing on the individual.

PMID- 29633873
TI  - Shifting intravenous therapy from hospital to the patient's home.

PMID- 29633875
TI  - Supporting community nurses to cope with patient suicide.

PMID- 29633874
TI  - Real-time simulation: first-hand experience of the challenges of community
      nursing for students.
AB  - The Community Challenge is a simulated community event for pre-registration
      nursing students across all four fields. Through the provision of real-time
      simulation, the Community Challenge has combined a deeper learning for both
      nursing students and the drama students who were involved in making the scenarios
      real and interactive. The event was run over 5 days, with positive evaluations
      from students and staff. Furthermore, Community Challenge has been found to be
      successful in expanding opportunities for students that align with national
      drivers, curriculum planning and interprofessional learning. The event has
      allowed students to engage in learning with other fields, enhancing their own
      practice. The Community Challenge has been found to enhance the link between
      theory and practice within primary care, promoting the relevance and importance
      of community care within nursing.

PMID- 29633876
TI  - Put resources into district nursing and reduce strain on the NHS.

PMID- 29633877
TI  - Nursing simulation: a community experience.
AB  - The education sector faces major challenges in providing learning experiences so
      that newly qualified nurses feel adequately prepared to work in a community
      setting. With this in mind, higher education institutions need to develop more
      innovative ways to deliver the community-nurse experience to student nurses. This
      paper presents and explores how simulation provides an opportunity for educators
      to support and evaluate student performance in an environment that models a
      complete patient encounter in the community. Following the simulation, evaluative
      data were collated and the answers analysed to identify key recommendations.

PMID- 29633878
TI  - Self-assessed competence among nurses working in municipal health-care services
      in Norway.
AB  - Demands made on nursing staff are expanding and changing, requiring a broad set
      of competencies that require evaluation and enhancement in places. This study
      used the Nurse Competence Scale to measure self-assessed competence among nurses
      working in three municipal health-care services in Norway. Results indicate that
      nurses perceive their competence as being satisfactory overall, but there are
      areas that would benefit from improvement: providing patients' family members
      with education and guidance, quality assurance, and using research to evaluate
      and develop services. These competencies could be the focus of departments'
      future competence plans. The Nurse Competence Scale can be used to assess the
      impact of training and the efficacy of competence-enhancing actions.

PMID- 29633880
TI  - Embracing palliative care within compassionate communities: a personal viewpoint.

PMID- 29633879
TI  - A guide to community mental health law for district nurses: the right to
      aftercare.
AB  - District nurses frequently provide physical care and treatment to patients in
      their own homes and care homes who have previously been detained under the Mental
      Health Act 1983 for the treatment of a mental illness. Such patients are commonly
      subject to community provisions of the Mental Health Act 1983 and it is important
      that districts nurses are aware of the implications of these provisions on the
      patients care and support. In this article the author considers a detained mental
      health patient's right to aftercare under the Mental Health Act 1983, section
      117.

PMID- 29633881
TI  - Gaps in Training in Interdisciplinary Social and Behavioral Sciences and
      Applications Among Undergraduate and Graduate Students in the 22 Top-Ranked
      Schools of Public Health in China.
AB  - The next generation of public health professionals requires rigorous training in
      behavioral health, in order to design effective behavioral interventions to
      respond effectively to the epidemiological transition in China. This study aimed
      to investigate issues in training in social and behavioral sciences in public
      health in China. A cross-sectional survey was conducted among 1285 and 835 last
      year undergraduate and graduate public health students in 2013. The results
      showed that (1) majority of undergraduate students but a minority of graduate
      students had enrolled in psychology, social medicine, and health promotion
      courses; (2) very few had enrolled in other social and behavioral sciences
      courses; (3) high percentages of students perceived significance, needs, and
      interests related to social sciences courses; (4) very few were familiar with
      commonly used behavioral health theories and constructs, or had applied such
      theories/constructs to their thesis. The situation deviates from international
      accreditation requirement. A timely review and benchmarking are warranted.

PMID- 29633882
TI  - Changes in ovarian reserve and ovarian blood flow in patients with polycystic
      ovary syndrome following laparoscopic ovarian drilling.
AB  - This prospective cohort study was conducted on 80 patients with clomiphene
      citrate (CC)-resistant polycystic ovary syndrome undergoing laparoscopic ovarian
      drilling (LOD). Pre- and post-LOD ovarian reserve parameters (anti-Mullerian
      hormone: AMH, ovarian volume: OV, and antral follicle count: AFC) and ovarian
      stromal blood flow indices (Vascularization index: VI, flow index: FI, and
      vascularization flow index: VFI) were measured to explore the effect of LOD and
      to find out the correlation between serum AMH and different clinical, hormonal,
      and ultrasonic variables. There was a highly significant reduction of the serum
      AMH (p < .001) after LOD with significant reduction in OV, AFC and vascular
      indices (VI, FI and VFI) of the right and left ovaries (p < .05). LOD
      significantly reduced ovarian reserve parameters (AMH, OV and AFC) and ovarian
      stromal blood flow indices (VI, FI and VFI) with no observed correlation between
      AMH levels and Doppler indices.

PMID- 29633883
TI  - Challenges and prospects in the diagnosis and treatment of primary central
      nervous system lymphoma.
AB  - INTRODUCTION: Primary central nervous system lymphoma (PCNSL) retains peculiar
      biological and clinical characteristics and a worse prognosis with respect to
      other comparable lymphomas. The need for high doses of chemotherapy to achieve
      valid drug concentrations in cerebral tissues and/or radiotherapy results in
      severe treatment-related toxicities, mainly neurologic, which are frequently as
      disabling as the disease itself. Areas covered: Several emerging combined
      therapies are addressed that focus on treating PCNSL. The prognosis has improved
      in the last years but several questions remain unanswered and the research of
      more effective therapies goes on. Information and data were obtained from direct
      authors' experience and a PubMed search of recent peer-reviewed original
      articles, review articles, and clinical guidelines. Expert commentary: The
      substantial progress observed in PCNSL has to be ascribed to a carefully
      combination of standard chemotherapeutic drugs. High-dose methotrexate-based
      polychemotherapy followed by mainteinance therapy offers one of the best chances
      to control the disease. Major issues that deserve many efforts by researchers are
      the definition of optimal consolidation treatment and a shared management of
      specific conditions such as elderly population and intra-ocular localization.

PMID- 29633884
TI  - Gelatinolytic activity of autocrine matrix metalloproteinase-9 leads to
      endothelial de-arrangement in Moyamoya disease.
AB  - Moyamoya disease (MMD) is a rare steno-occlusive cerebrovascular disorder.
      Mechanisms driving the formation of aberrant MMD vessels remain elusive. We
      collected serum and vessel specimens from MMD and atherosclerotic cerebrovascular
      disease (ACVD) patients serving as controls due to the same hypoxic stimulus but
      substantial differences in terms of vascular features. Based on patient material
      and an in vitro model mimicking ACVD and MMD conditions, matrix metalloproteinase
      9 (MMP-9) and vascular-endothelial growth factor (VEGF) were tested for their
      potential involvement in cerebrovascular disintegration. While serum
      concentration of both molecules did not significantly differ in both patient
      groups, excessive collagenase activity and lowered collagen IV protein amount in
      MMD vessels pointed to a focal MMP-9 activity at the affected vessel sites. We
      observed overexpressed and autocrinely secreted MMP-9 and VEGF along with
      disturbances of EC-matrix interactions in MMD but not ACVD serum-treated cEND
      cells. These seemingly brain-specific effects were partially attenuated by VEGF
      signaling inhibition suggesting its role in the MMD etiology. In conclusion, our
      findings support the understanding of the high incidence of hemorrhagic and
      ischemic events in MMD and provide the basis for novel therapeutic strategies
      stopping or slowing the development of fragile cerebrovasculature or micro-bleeds
      characterizing the disease.

PMID- 29633885
TI  - Comparison of the montreal cognitive assessment and the mini-mental state
      examination as screening tests in hemodialysis patients without symptoms.
AB  - Cognitive impairment in end-stage renal disease patients is associated with an
      increased risk of mortality. We examined the cognitive function in hemodialysis
      (HD) patients and compared the Korean versions of the Montreal Cognitive
      Assessment (K-MoCA) and of the Mini-Mental State Examination (K-MMSE) to identify
      the better cognitive screening instrument in these patients. Thirty patients
      undergoing hemodialysis and 30 matched reference group of apparently healthy
      control were included. All subjects underwent the K-MoCA, K-MMSE and a
      neuropsychological test battery to measure attention, visuospatial function,
      language, memory and executive function. All cognitive data were converted to z
      scores with appropriate age and education level prior to group comparisons.
      Cognitive performance 1.0 SD below the mean was defined as modest cognitve
      impairment while 1.5 below the mean was defined as severe cognitive impairment.
      Modest cognitive impairment in memory plus other cognitive domains was detected
      in 27 patients (90%) while severe cognitive impairment in memory plus other
      cognitive domains was detected in 23 (77%) patients. Total scores in the K-MoCA
      were significantly lower in HD patients than in the reference group. However, no
      significant group difference was found in the K-MMSE. The K-MMSE ROC AUC (95%
      confidence interval) was 0.72 (0.59-0.85) and K-MoCA ROC AUC was 0.77 (0.65
      0.89). Cognitive impairment is common but under-diagnosed in this population. The
      K-MoCA seems to be more sensitive than the K-MMSE in HD patients.

PMID- 29633886
TI  - Comorbidities, risk factors and outcomes in patients with heart failure and an
      ejection fraction of more than or equal to 40% in primary care- and hospital care
      based outpatient clinics.
AB  - OBJECTIVE: The aim of this study is to describe patients with heart failure and
      an ejection fraction (EF) of more than or equal to 40%, managed in both Primary-
      and Hospital based outpatient clinics separately with their prognosis,
      comorbidities and risk factors. Further to compare the heart failure medication
      in the two groups. DESIGN: We used the prospective Swedish Heart Failure Registry
      to include 9654 out-patients who had HF and EF >=40%, 1802 patients were
      registered in primary care and 7852 in hospital care. Descriptive statistical
      tests were used to analyze base line characteristics in the two groups and
      multivariate logistic regression analysis to assess mortality rate in the groups
      separately. SETTING: The prospective Swedish Heart Failure Registry. SUBJECTS:
      Patients with heart failure and an ejection fraction (EF) of more than or equal
      to 40%. MAIN OUTCOME MEASURES: Comorbidities, risk factors and mortality.
      RESULTS: Mean-age was 77.5 (primary care) and 70.3 years (hospital care) p <
      0.0001, 46.7 vs. 36.3% women respectively (p < 0.0001) and EF >=50% 26.1 vs.
      13.4% (p < 0.0001). Co-morbidities were common in both groups (97.2% vs. 92.3%),
      the primary care group having more atrial fibrillation, hypertension, ischemic
      heart disease and COPD. According to the multivariate logistic regression
      analysis smoking, COPD and diabetes were the most important independent risk
      factors in the primary care group and valvular disease in the hospital care
      group. All-cause mortality during mean follow-up of almost 4 years was 31.5% in
      primary care and 27.8% in hospital care. One year-mortality rates were 7.8%, and
      7.0% respectively. CONCLUSION: Any co-morbidity was noted in 97% of the HF
      patients with an EF of more than or equal to 40% managed at primary care based
      out-patient clinics and these patients had partly other independent risk factors
      than those patients managed in hospital care based outpatients clinics. Our
      results indicate that more attention should be payed to manage COPD in the
      primary care group. KEY POINTS 97% of heart failure patients with an ejection
      fraction of more than or equal to 40% managed at primary care based out-patient
      clinics had any comorbidity. Patients in primary care had partly other
      independent risk factors than those in hospital care. All-cause mortality during
      mean follow-up of almost 4 years was higher in primary care compared to hospital
      care. In matched HF-patients RAS-antagonists, beta-blockers as well as the
      combination of the two drugs were more seldom prescribed when managed in primary
      care compared with hospital care.

PMID- 29633887
TI  - Diabetic retinopathy may predict the renal outcomes of patients with diabetic
      nephropathy.
AB  - BACKGROUND: The patients with Type 2 diabetes mellitus (T2DM) and diabetic
      retinopathy (DR) are prone to develop diabetic nephropathy (DN). In this study,
      we aimed to clarify the relationship between DR and the progression of DN in
      patients with T2DM. METHODS: In the cross-section study, 250 patients with T2DM
      and biopsy-proven DN were divided into two groups: 130 in the DN without DR group
      (DN group) and 120 in the DN + DR group. Logistic regression analysis was
      performed to identify risk factors for DR. Of the above 250 patients, 141 were
      recruited in the cohort study who received follow-up for at least 1 year and the
      influence of DR on renal outcome was assessed using Cox regression. Renal outcome
      was defined as the progression to end-stage renal disease (ESRD). RESULTS: In the
      cross-section study, the severity of glomerular lesions (class IIb + III) and DM
      history >10 years were significantly associated with the odds of DR when
      adjusting for baseline proteinuria, hematuria, e-GFR, and interstitial
      inflammation. In the cohort study, a multivariate COX analysis demonstrated that
      the DR remained an independent risk factor for progression to ESRD when adjusting
      for important clinical variables and pathological findings (p < .05).
      CONCLUSIONS: These findings indicated that the severity of glomerular lesions was
      significantly associated with DR and DR was an independent risk factor for the
      renal outcomes in patients with DN, which suggested that DR may predict the renal
      prognosis of patients with T2DM and DN.

PMID- 29633889
TI  - Prenatal reflex DNA screening for trisomy 21, 18 and 13.

PMID- 29633891
TI  - Correction to: Inhibitors of alanine racemase enzyme: a review.

PMID- 29633890
TI  - Risk factors associated with self-reported injury history in female youth soccer
      players.
AB  - BACKGROUND: studies that investigate risk factors for musculoskeletal injuries in
      female youth athletes are limited, especially related to training attributes and
      position status. OBJECTIVE: to determine risk factors including training
      attributes and position status for a self-reported musculoskeletal injury history
      in female youth soccer players. METHODS: we conducted a cross-sectional study of
      young female soccer players (mean age: 13.6 +/- 2.3 years). we asked about their
      history of musculoskeletal injuries using an electronic questionnaire. the
      proportion of young female soccer players with and without a history of soccer
      related musculoskeletal injuries were compared based on physical characteristics,
      training attributes, position status (single vs. multiple), lower extremity
      strength, and joint laxity. a binary logistic regression analysis was used to
      generate, and adjusted odds ratios adjusted for potential co-variates (aor). a
      95% confidence interval (95%ci) that did not cross one or p < 0.05 were
      considered statistically significant. RESULTS: a total of 160 young female soccer
      players (mean age: 13.6 +/- 2.3 years) participated in the study. an independent
      association was found between prior musculoskeletal injuries and older ages (aor:
      1.60, 95%ci: 1.17, 2.20, p = 0.004), higher weight (aor: 1.10, 95%ci: 1.01, 1.20,
      p = 0.026), and greater bmi (aor: 1.43, 95%ci: 1.07, 1.90, p = 0.014).
      CONCLUSIONS: musculoskeletal injuries were associated with age, weight, and bmi
      in female youth players. the current study indicates that maintaining proper body
      composition may be beneficial to reduce musculoskeletal injuries among female
      youth soccer players.

PMID- 29633888
TI  - Expanding syphilis testing: a scoping review of syphilis testing interventions
      among key populations.
AB  - INTRODUCTION: Syphilis is an important sexually transmitted infection (STI).
      Despite inexpensive and effective treatment, few key populations receive syphilis
      testing. Innovative strategies are needed to increase syphilis testing among key
      populations. Areas covered: This scoping review focused on strategies to increase
      syphilis testing in key populations (men who have sex with men (MSM), sex
      workers, people who use drugs, transgender people, and incarcerated individuals).
      Expert commentary: We identified many promising syphilis testing strategies,
      particularly among MSM. These innovations are separated into diagnostic, clinic
      based, and non-clinic based strategies. In terms of diagnostics, self-testing,
      dried blood spots, and point-of-care testing can decentralize syphilis testing.
      Effective syphilis self-testing pilots suggest the need for further attention and
      research. In terms of clinic-based strategies, modifying default clinical
      procedures can nudge physicians to more frequently recommend syphilis testing. In
      terms of non-clinic based strategies, venue-based screening (e.g. in correctional
      facilities, drug rehabilitation centres) and mobile testing units have been
      successfully implemented in a variety of settings. Integration of syphilis with
      HIV testing may facilitate implementation in settings where individuals have
      increased sexual risk. There is a strong need for further syphilis testing
      research and programs.

PMID- 29633892
TI  - Pharmacological and biotechnological advances with Rosmarinus officinalis L.
AB  - INTRODUCTION: Rosmarinus officinalis L. is an aromatic plant with a number of
      biological properties. Recently, has been studied regarding its therapeutic
      potential. The objective of this study was to perform a systematic review on R.
      officinalis essential oil for its pharmacological properties and biotechnological
      applications. Areas covered: The databases were searched for articles (Science
      Direct, Pub Med and Web of Science) and patents (INPI, WIPO and EPO) with
      publications on R. officinalis and associations with essential oil (EO-Ro),
      cardiovascular system, hypertension and cyclodextrin. We selected 305 articles on
      EO-Ro in the most diverse subjects and six articles with of R. officinalis
      associated with hypertension. 59 patents were analyzed. The results demonstrate
      how extensive the studies are on the biological activities with the extract and
      EO-Ro. These have shown effects antibacterial, antifungal, anti-inflammatory,
      antitumor and other. The properties exhibited by EO-Ro reinforce the use of this
      plant as a phytotherapeutic agent. Expert opinion: Although there are several
      pharmacological properties, studies on the prevention or treatment of
      cardiovascular diseases with EO-Ro are scarce, especially to evaluate the
      antihypertensive activity of EO-Ro. It has also become clear that EO-Ro can be
      exploited in different commercial products as supplement, cosmetics and new
      formulations.

PMID- 29633894
TI  - Eugene T. Lyons.

PMID- 29633893
TI  - A comprehensive analysis of Wnt/beta-catenin signaling pathway-related genes and
      crosstalk pathways in the treatment of As2O3 in renal cancer.
AB  - We aimed to investigate the effect of As2O3 treatment on Wnt/beta-catenin
      signaling pathway-related genes and pathways in renal cancer. Illumina-based RNA
      seq of 786-O cells with or without As2O3 treatment was performed, and
      differentially expressed genes (DEGs) were identified using Cuffdiff software.
      TargetMine was utilized to perform Gene Ontology (GO) pathway and Disease
      Ontology enrichment analyses. Furthermore, TRANSFAC database and LPIA method were
      applied to select differentially expressed transcription factors (TFs) and
      pathways related to Wnt/beta-catenin signaling pathway, respectively.
      Additionally, transcriptional regulatory and pathway crosstalk networks were
      constructed. In total, 1684 DEGs and 69 TFs were screened out. The 821 up
      regulated DEGs were mainly enriched in 67 pathways, 70 GO terms, and 46 disease
      pathways, while only 1 pathway and 5 GO terms were enriched for 863 down
      regulated DEGs. A total of 18 DEGs (4 up-regulated and 14 down-regulated genes)
      were involved in the Wnt/beta-catenin signaling pathway. Among the 18 DEGs, 4
      ones were TFs. Furthermore, 211 pathways were predicted to be linked to the
      Wnt/beta-catenin signaling pathway. In conclusion, As2O3 may have a significant
      effect on the Wnt/beta-catenin signaling pathway for renal cancer treatment. The
      potential key DEGs are expected to be used as therapeutic targets.

PMID- 29633895
TI  - Introduction: Just Say No? New Insights About Change Versus Constancy in
      Substance Use Behavioral Decisions in Youth With and Without ADHD.
AB  - Despite enormous social-psychological and economic consequences of substance
      abuse in youth and young adults, too little is known about effective
      interventions among substance users, both with and without ADHD. This special
      issue reports on four linked investigations that employed a novel research
      strategy when the Multimodal Treatment Children with ADHD Study (MTA)
      participants were between ages 21.7 and 27.3 years old (14-16 years after initial
      assessments). Using combination of in-depth qualitative narrative interviews and
      quantitative analyses ("mixed methods") of 183 participants from four to six
      original MTA sites, investigators sought to obtain a more complete understanding
      of factors contributing to youths' substance use (SU) initiation, maintenance,
      and desistence, (both among youth with ADHD and control participants). The
      articles in this special issue illuminate important new insights about possible
      influences contributing to SU, particularly persistent use/abuse. Findings also
      illustrate the benefits of mixed-methods studies, not only to better understand
      the linkages between ADHD and SU, but also to understand other areas of
      child/adult psychopathology.

PMID- 29633896
TI  - THERPA: A small molecule database related to prion protein regulation and prion
      diseases progression.
AB  - Prion diseases are fatal neurodegenerative disorders that affect humans and
      animals. Although various small molecules have been evaluated for application in
      the treatment of prion diseases, none have been shown to be efficacious.
      Expanding our knowledge of these molecules is important for understanding of the
      complex mechanisms of prion diseases. To improve access to the scattered
      information on small molecules related to prion diseases, we built a database of
      therapeutic molecules associated with prion diseases (THERPA,
      therpa.pythonanywhere.com). THERPA includes 119 small molecules and their 283
      relationships with prion diseases. THERPA is an interactive visual database and
      useful for improving search efficiency which can help researchers identify
      intrinsic small molecules that can be used for developing therapeutics for prion
      diseases.

PMID- 29633897
TI  - Clinical aspects of Emery-Dreifuss muscular dystrophy.
AB  - Emery-Dreifuss muscular dystrophy (EDMD), clinically characterized by scapulo
      humero-peroneal muscle atrophy and weakness, multi-joint contractures with spine
      rigidity and cardiomyopathy with conduction defects, is associated with
      structural/functional defect of genes that encode the proteins of nuclear
      envelope, including lamin A and several lamin-interacting proteins. This paper
      presents clinical aspects of EDMD in context to causative genes, genotype
      phenotype correlation and its emplacement within phenotypic spectrum of skeletal
      muscle diseases associated with envelopathies.

PMID- 29633899
TI  - Predictors of Nursing Facility Entry by Medicaid-Only Older Adults and Persons
      With Disabilities in California.
AB  - Nearly one-third of adult Medicaid beneficiaries who receive long-term services
      and supports (LTSS) consist of older adults and persons with disabilities who are
      not eligible for Medicare. Beneficiaries, advocates, and policymakers have all
      sought to shift LTSS to home and community settings as an alternative to
      institutional care. We conducted a retrospective cohort study of Medicaid-only
      adults in California with new use of LTSS in 2006-2007 (N = 31 849) to identify
      unique predictors of entering nursing facilities versus receiving Medicaid home
      and community-based services (HCBS). Among new users, 18.3% entered into nursing
      facilities, whereas 81.7% initiated HCBS. In addition to chronic conditions,
      functional and cognitive limitations, substance abuse disorders (odds ratio [OR]
      1.35; 95% confidence interval [CI]: 1.23, 1.48), and homelessness (OR: 4.35, 9%
      CI: 3.72, 5.08) were associated with higher odds of nursing facility entry. For
      older adults and persons with disabilities covered by Medicaid only, integration
      with housing and behavioral health services may be key to enabling beneficiaries
      to receive LTSS in noninstitutional settings.

PMID- 29633900
TI  - From portable dialysis to a bioengineered kidney.
AB  - INTRODUCTION: Since the advent of peritoneal dialysis (PD) in the 1970s, the
      principles of dialysis have changed little. In the coming decades, several major
      breakthroughs are expected. Areas covered: Novel wearable and portable dialysis
      devices for both hemodialysis (HD) and PD are expected first. The HD devices
      could facilitate more frequent and longer dialysis outside of the hospital, while
      improving patient's mobility and autonomy. The PD devices could enhance blood
      purification and increase technique survival of PD. Further away from clinical
      application is the bioartificial kidney, containing renal cells. Initially, the
      bioartificial kidney could be applied for extracorporeal treatment, to partly
      replace renal tubular endocrine, metabolic, immunoregulatory and secretory
      functions. Subsequently, intracorporeal treatment may become possible. Expert
      commentary: Key factors for successful implementation of miniature dialysis
      devices are patient attitudes and cost-effectiveness. A well-functioning and safe
      extracorporeal blood circuit is required for HD. For PD, a double lumen PD
      catheter would optimize performance. Future research should focus on further
      miniaturization of the urea removal strategy. For the bio-artificial kidney
      (BAK), cost effectiveness should be determined and a general set of functional
      requirements should be defined for future studies. For intracorporeal
      application, water reabsorption will become a major challenge.

PMID- 29633898
TI  - Reactivation of endogenous retroviral elements via treatment with DNMT- and HDAC
      inhibitors.
AB  - Inhibitors of DNA methyltransferases (DNMTis) or histone deacetylases (HDACis)
      are epigenetic drugs which are investigated since decades. Several have been
      approved and are applied in the treatment of hematopoietic and lymphatic
      malignancies, although their mode of action has not been fully understood. Two
      recent findings improved mechanistic insights: i) activation of human endogenous
      retroviral elements (HERVs) with concomitant synthesis of double-stranded RNAs
      (dsRNAs), and ii) massive activation of promoters from long terminal repeats
      (LTRs) which originated from past HERV invasions. These dsRNAs activate an
      antiviral response pathway followed by apoptosis. LTR promoter activation leads
      to synthesis of non-annotated transcripts potentially encoding novel or cryptic
      proteins. Here, we discuss the current knowledge of the molecular effects exerted
      by epigenetic drugs with a focus on DNMTis and HDACis. We highlight the role in
      LTR activation and provide novel data from both in vitro and in vivo epigenetic
      drug treatment.

PMID- 29633901
TI  - Orthosteric and benzodiazepine cavities of the alpha1beta2gamma2 GABAA receptor:
      insights from experimentally validated in silico methods.
AB  - gamma-aminobutyric acid-type A (GABAA) receptors mediate fast synaptic inhibition
      in the central nervous system of mammals. They are modulated via several sites by
      numerous compounds, which include GABA, benzodiazepines, ethanol, neurosteroids
      and anaesthetics among others. Due to their potential as targets of novel drugs,
      a detailed knowledge of their structure-function relationships is needed. Here,
      we present the model of the alpha1beta2gamma2 subtype GABAA receptor in the APO
      state and in complex with selected ligands, including agonists, antagonists and
      allosteric modulators. The model is based on the crystallographic structure of
      the human beta3 homopentamer GABAA receptor. The complexes were refined using
      atomistic molecular dynamics simulations. This allowed a broad description of the
      binding modes and the detection of important interactions in agreement with
      experimental information. From the best of our knowledge, this is the only model
      of the alpha1beta2gamma2 GABAA receptor that represents altogether the
      desensitized state of the channel and comprehensively describes the interactions
      of ligands of the orthosteric and benzodiazepines binding sites in agreement with
      the available experimental data. Furthermore, it is able to explain small
      differences regarding the binding of a variety of chemically divergent ligands.
      Finally, this new model may pave the way for the design of focused experimental
      studies that will allow a deeper description of the receptor.

PMID- 29633902
TI  - Pediatric irritable bowel syndrome and other functional abdominal pain disorders:
      an update of non-pharmacological treatments.
AB  - INTRODUCTION: Functional abdominal pain disorders, including irritable bowel
      syndrome, are common in children and treatment can often be difficult.
      Pharmacological therapies and complementary treatments are widely used, despite
      the limited data in pediatrics. Areas covered: This review provides an overview
      of the available data for the use of diet, probiotics, percutaneous electrical
      nerve stimulation, and psychosocial interventions, including hypnotherapy, yoga,
      cognitive and behavioral therapy, and mind-body interventions for the treatment
      of functional abdominal pain disorders in children. The literature review
      included a PubMed search by each therapy, children, abdominal pain, and irritable
      bowel syndrome. Relevant articles to this review are discussed. Expert
      commentary: The decision on the use of pharmacological and complementary
      therapies should be based on clinical findings, evidence, availability, and in
      depth discussion with the patient and family. The physician should provide
      education on the different interventions and their role on the treatment in an
      empathetic and warm manner providing ample time for the family to ask questions.

PMID- 29633903
TI  - The role of neoadjuvant chemotherapy in ovarian cancer.
AB  - INTRODUCTION: Ovarian cancer is mostly diagnosed at advanced stage. Better
      survival is achieved through complete debulking surgery and chemotherapy.
      Historically, neoadjuvant chemotherapy (NAC) has been introduced for unresectable
      disease to decrease tumor load and perform a unique complete surgery. Four
      randomized control trials have compared primary debulking surgery to NAC, but
      there is still controversy about the use of neoadjuvant chemotherapy and
      questions about its modalities. Areas covered: We made a review of knowledge on
      benefits of NAC compared to primary debulking chemotherapy, in terms of survival
      and morbidity, methods of administration, new drugs in early and late phase
      trials, the selection of patients. Similar survival was observed after NAC and
      interval debulking surgery or primary debulking surgery. Morbidity of surgery was
      decreased after interval debulking compared primary debulking surgery.
      Conventional drugs are carboplatin and paclitaxel. Safety of bevacizumab was
      evaluated in phase 2 trials associated with conventional drugs. Immunotherapy
      trials are enrolling patients in phase 1 study. Expert commentary: NAC followed
      by debulking surgery is the best treatment for patients with advanced ovarian
      cancer.

PMID- 29633904
TI  - Metabolic reprogramming enables hepatocarcinoma cells to efficiently adapt and
      survive to a nutrient-restricted microenvironment.
AB  - Hepatocellular carcinoma (HCC) is a metabolically heterogeneous cancer and the
      use of glucose by HCC cells could impact their tumorigenicity. Dt81Hepa1-6 cells
      display enhanced tumorigenicity compared to parental Hepa1-6 cells. This
      increased tumorigenicity could be explained by a metabolic adaptation to more
      restrictive microenvironments. When cultured at high glucose concentrations,
      Dt81Hepa1-6 displayed an increased ability to uptake glucose (P<0.001), increased
      expression of 9 glycolytic genes, greater GTP and ATP (P<0.001), increased
      expression of 7 fatty acid synthesis-related genes (P<0.01) and higher levels of
      Acetyl-CoA, Citrate and Malonyl-CoA (P<0.05). Under glucose-restricted
      conditions, Dt81Hepa1-6 used their stored fatty acids with increased expression
      of fatty acid oxidation-related genes (P<0.01), decreased triglyceride content
      (P<0.05) and higher levels of GTP and ATP (P<0.01) leading to improved
      proliferation (P<0.05). Inhibition of lactate dehydrogenase and aerobic
      glycolysis with sodium oxamate led to decreased expression of glycolytic genes,
      reduced lactate, GTP and ATP levels (P<0.01), increased cell doubling time
      (P<0.001) and reduced fatty acid synthesis. When combined with cisplatin, this
      inhibition led to lower cell viability and proliferation (P<0.05). This metabolic
      induced tumorigenicity was also reflected in human Huh7 cells by a higher glucose
      uptake and proliferative capacity compared to HepG2 cells (P<0.05). In HCC
      patients, increased tumoral expression of Glut-1, Hexokinase II and Lactate
      dehydrogenase correlated with poor survival (P = 2.47E-5, P = 0.016 and P = 6.58E
      5). In conclusion, HCC tumorigenicity can stem from a metabolic plasticity
      allowing them to thrive in a broader range of glucose concentrations. In HCC,
      combining glycolytic inhibitors with conventional chemotherapy could lead to
      improved treatment efficacy.

PMID- 29633905
TI  - Insights into the structure-function relationship of brown plant hopper
      resistance protein, Bph14 of rice plant: a computational structural biology
      approach.
AB  - Brown plant hopper (BPH) is one of the major destructive insect pests of rice,
      causing severe yield loss. Thirty-two BPH resistance genes have been identified
      in cultivated and wild species of rice Although, molecular mechanism of rice
      plant resistance against BPH studied through map-based cloning, due to non
      existence of NMR/crystal structures of Bph14 protein, recognition of leucine-rich
      repeat (LRR) domain and its interaction with different ligands are poorly
      understood. Thus, in the present study, in silico approach was adopted to predict
      three-dimensional structure of LRR domain of Bph14 using comparative modelling
      approach followed by interaction study with jasmonic and salicylic acids. LRR
      domain along with LRR-jasmonic and salicylic acid complexes were subjected to
      dynamic simulation using GROMACS, individually, for energy minimisation and
      refinement of the structure. Final binding energy of jasmonic and salicylic acid
      with LRR domain was calculated using MM/PBSA. Free-energy landscape analysis
      revealed that overall stability of LRR domain of Bph14 is not much affected after
      forming complex with jasmonic and salicylic acid. MM/PBSA analysis revealed that
      binding affinities of LRR domain towards salicylic acid is higher as compared to
      jasmonic acid. Interaction study of LRR domain with salicylic acid and jasmonic
      acid reveals that THR987 of LRR form hydrogen bond with both complexes. Thus,
      THR987 plays active role in the Bph14 and phytochemical interaction for inducing
      resistance in rice plant against BPH. In future, Bph14 gene and phytochemicals
      could be used in BPH management and development of novel resistant varieties for
      increasing rice yield.

PMID- 29633906
TI  - Empathic responses are reduced to competitive but not non-competitive outgroups.
AB  - Individuals feel more empathy for those in their group (i.e. ingroup members)
      than those who are not (i.e. outgroup members). But empathy is not merely
      selective to group distinctions, rather it fluctuates according to how groups are
      perceived. The goal of this research was to determine whether group-based
      evaluations can drive biases in self-reported empathy as well as in the
      underlying neural activity. Participants were asked to rate a target's physical
      pain while BOLD responses were recorded via functional magnetic resonance imaging
      (fMRI). The target was either a member of the ingroup or one of two outgroups,
      one which was more of a rival to the ingroup than the other. Participants
      reported feeling more empathy for targets experiencing painful compared to
      innocuous events, showing bias only in favour of their ingroup. Neural responses
      were stronger while observing painful, compared to innocuous, events but only for
      targets from the ingroup or the less competitive outgroup. The difference was non
      significant and trended in the opposite direction when the target was from the
      more competitive outgroup. This provides evidence that empathy is not merely
      selective to "us" vs "them" but is more nuanced by whom we refer to by "them".

PMID- 29633907
TI  - Strategic accident reduction in an energy company and its resulting financial
      benefits.
AB  - This study provides a case example of an energy company that prioritized
      occupational safety and health and accident reduction as long-term, strategic
      development targets. Furthermore, this study describes the monetary benefits of
      this strategic decision. Company-specific accident indicators and monetary costs
      and benefits are evaluated. During the observation period (2010-2016), strategic
      investments in occupational safety and health cost the company EUR 0.8 million.
      However, EUR 1.8 million were saved in the same period, resulting in a 2.20 cost
      benefit ratio. The trend in cost savings is strongly positive. Annual accident
      costs were EUR 0.4 million lower in 2016 compared to costs in 2010. This study
      demonstrates that long-term, strategic commitment to occupational safety and
      health provides monetary value.

PMID- 29633908
TI  - Molecular dynamics simulation and binding free energy studies of novel leads
      belonging to the benzofuran class inhibitors of Mycobacterium tuberculosis
      Polyketide Synthase 13.
AB  - In this work, the binding mechanism of new Polyketide Synthase 13 (Pks13)
      inhibitors has been studied through molecular dynamics simulation and free energy
      calculations. The drug Tam1 and its analogs, belonging to the benzofuran class,
      were submitted to 100 ns simulations, and according to the results obtained for
      root mean square deviation, all the simulations converged from approximately 30
      ns. For the analysis of backbone flotation, the root mean square fluctuations
      were plotted for the Calpha atoms; analysis revealed that the greatest
      fluctuation occurred in the residues that are part of the protein lid domain. The
      binding free energy value (DeltaGbind) obtained for the Tam16 lead molecule was
      of -51.43 kcal/mol. When comparing this result with the DeltaGbind values for the
      remaining analogs, the drug Tam16 was found to be the highest ranked: this result
      is in agreement with the experimental results obtained by Aggarwal and
      collaborators, where it was verified that the IC50 for Tam16 is the smallest
      necessary to inhibit the Pks13 (IC50 = 0.19 MUM). The energy decomposition
      analysis suggested that the residues which most interact with inhibitors are:
      Ser1636, Tyr1637, Asn1640, Ala1667, Phe1670, and Tyr1674, from which the greatest
      energy contribution to Phe1670 was particularly notable. For the lead molecule
      Tam16, a hydrogen bond with the hydroxyl of the phenol not observed in the other
      analogs induced a more stable molecular structure. Aggarwal and colleagues
      reported this hydrogen bonding as being responsible for the stability of the
      molecule, optimizing its physic-chemical, toxicological, and pharmacokinetic
      properties.

PMID- 29633909
TI  - Cultural expressions of depression and the development of the Indonesian
      Depression Checklist.
AB  - Depression may manifest differently across cultural settings, suggesting the
      value of an assessment tool that is sensitive enough to capture these variations.
      The study reported in this article aimed to develop a depression screening tool
      for Indonesians derived from ethnographic interviews with 20 people who had been
      diagnosed as having depression by clinical psychologists at primary health
      centers. The tool, which we have termed the Indonesian Depression Checklist
      (IDC), consists of 40 items. The tool was administered to 125 people assessed to
      have depression by 40 clinical psychologists in primary health centers. The data
      were analyzed with Confirmatory Factor Analysis (CFA) (IBM SPSS AMOS Software).
      CFA identified a five-factor hierarchical model ( chi 2 = 168.157, p = .091; CFI
      = .963; TLI = .957; RMSEA = .036). A 19-item inventory of the IDC, with five
      factors - Physical Symptoms, Affect, Cognition, Social Engagement and Religiosity
      - was identified. There was a strong correlation between the total score of the
      IDC and total score of the Center for Epidemiological Studies-Depression scale
      (revised version CES-D), a standard tool for assessing symptoms of depression.
      The IDC accommodates culturally distinctive aspects of depression among
      Indonesians that are not included in the CES-D.

PMID- 29633910
TI  - Interaction of flavonols with human serum albumin: a biophysical study showing
      structure-activity relationship and enhancement when coated on silver
      nanoparticles.
AB  - Binding affinities of flavonols namely quercetin, myricetin, and kaempferol to
      human serum albumin (HSA) were determined fluorimetrically and the order was
      observed to be myricetin > quercetin > kaempferol demonstrating structure
      activity relationship. Quercetin-coated silver nanoparticles (AgNPs) show higher
      binding affinity to HSA compared to free quercetin with binding constants 6.04 *
      107 M-1 and 4.2 * 106 M-1, respectively. Using site-specific markers it is
      concluded that free quercetin and that coated on AgNPs bind at different sites.
      Significant structural changes in circular dichroism (CD) spectra of HSA were
      recorded with quercetin-coated AgNPs compared to free quercetin. These results
      were further substantiated by time-resolved fluorescence spectroscopy where
      fluorescence life time of the tryptophan residue in HSA-quercetin-coated AgNPs
      complex decreased to 3.63 ns from 4.22 ns in HSA-quercetin complex. Isothermal
      calorimetric studies reveal two binding modes for quercetin-coated AgNPs and also
      higher binding constants compared to free quercetin. These higher binding
      affinities are attributed to altered properties of quercetin when coated on AgNPs
      enabling it to reach the binding sites other than site II where free quercetin
      mainly binds.

PMID- 29633911
TI  - A structural comparison of 'real' and 'model' calmodulin clarified allosteric
      interactions regulating domain motion.
AB  - Calmodulin (CaM) is a multifunctional calcium-binding protein, which regulates
      various biochemical processes. CaM acts via structural changes and complex
      forming with its target enzymes. CaM has two globular domains (N-lobe and C-lobe)
      connected by a long linker region. Upon calcium binding, the N-lobe and C-lobe
      undergo local conformational changes, after that, entire CaM wraps the target
      enzyme through a large conformational change. However, the regulation mechanism,
      such as allosteric interactions regulating the conformational changes, is still
      unclear. In order to clarify the allosteric interactions, in this study,
      experimentally obtained 'real' structures are compared to 'model' structures
      lacking the allosteric interactions. As the allosteric interactions would be
      absent in calcium-free CaM (apo-CaM), allostery-eliminated calcium-bound CaM
      (holo-CaM) models were constructed by combining the apo-CaM's linker and the holo
      CaM's N- and C-lobe. Before the comparison, the 'real' and 'model' structures
      were clustered and cluster-cluster relationship was determined by a principal
      component analysis. The structures were compared based on the relationship, then,
      a distance map and a contact probability analysis clarified that the inter-domain
      motion is regulated by several groups of inter-domain contacting residue pairs.
      The analyses suggested that these residues cause inter-domain translation and
      rotation, and as a consequence, the motion encourage structural diversity. The
      resultant diversity would contribute to the functional versatility of CaM.

PMID- 29633912
TI  - DNA Topoisomerase IB as a Potential Ionizing Radiation Exposure and Dose
      Biomarker.
AB  - In radiation exposure scenarios where physical dosimetry is absent or
      inefficient, dose estimation must rely on biological markers. A reliable
      biomarker is of utmost importance in correlating biological system changes with
      radiation exposure. Human DNA topoisomerase IB (topo I) is a ubiquitous nuclear
      enzyme, which is involved in essential cellular processes, including
      transcription, DNA replication and DNA repair, and is the target of anti-cancer
      drugs. It has been shown that the cellular activity of this enzyme is
      significantly sensitive to various DNA lesions, including radiation-induced DNA
      damages. Therefore, we investigated the potential of topo I as a biomarker of
      radiation exposure and dose. We examined the effect of exposure of different
      human cells to beta, X-ray and gamma radiation on the cellular catalytic activity
      of topo I. The results demonstrate a significant reduction in the DNA relaxation
      activity of topo I after irradiation and the level of the reduction was
      correlated with radiation dose. In normal human peripheral blood lymphocytes,
      exposure for 3 h to an integral dose of 0.065 mGy from tritium reduced the enzyme
      activity to less than 25%. In MG-63 osteoblast-like cells and in human pulmonary
      fibroblast (HPF) cells exposed to gamma radiation from a 60Co source (up to 2 Gy)
      or to X rays (up to 2.8 Gy), a significant decrease in topo I catalytic activity
      was also observed. We observed that the enzyme-protein level was not altered but
      was partially posttranslational modified by ADP-ribosylation of the enzyme
      protein that is known to reduce topo I activity. The results of this study
      suggest that the decrease in the cellular topo I catalytic activity after low
      dose exposure to different radiation types may be considered as a novel biomarker
      of ionizing radiation exposure and dose. For this purpose, a suitable ELISA-based
      method for large-scale analysis of radiation-induced topo I modification is under
      development.

PMID- 29633913
TI  - The use of pyrosequencing for detection of hemagglutinin mutations associated
      with increased pathogenicity of H5N1 avian influenza viruses in mammals.
AB  - Hemagglutinin (HA) cleavage is critical for virulence of influenza viruses. The
      amino acid residue at the P6 position of the HA cleavage site (HACS) has been
      shown to be most variable and to have a direct correlation with the cleavage
      efficiency and pathogenicity of H5N1 avian influenza viruses (AIVs) in mammals.
      Among these amino acid variants, serine has been associated with the highest
      virulence in mammals, and its detection may serve as an indicator for H5N1 AIVs
      with high pathogenicity and potential public risk. We developed a rapid detection
      method based on reverse-transcription (RT)-PCR and pyrosequencing to detect a
      mutation at the HACS that is associated with increased pathogenicity of H5N1 AIVs
      in mammals. Herein, we provide a specific, sensitive, and reliable method for
      rapid detection of one of the virulence determinants associated with increased
      pathogenicity of H5N1 AIVs in mammals.

PMID- 29633914
TI  - What am I? A philosophical account of personhood and its applications to people
      with brain injury.
AB  - This article identifies the dilemma faced by clinical staff when asked to support
      the withdrawal of clinically assisted nutrition and hydration in a patient in a
      vegetative state. On the one hand, they are expected to treat the patient as a
      person in their daily interactions; on the other, they are asked to withdraw
      treatment on the grounds that it is futile, which may seem to run counter to
      treating people as persons. The article highlights that similar debates exist
      within the philosophical community about the nature of personhood and describes
      two philosophical accounts of personhood. The aim is to help clinicians
      articulate the reasons for their intuitions more clearly, and thus justify their
      beliefs.

PMID- 29633915
TI  - Perioperative anaesthetic adverse events in Thailand (PAAd THAI) study: Incident
      report of perioperative convulsion.
AB  - The aim of this study was to identify the characteristics of perioperative
      convulsion and to suggest possible correcting strategies. The multi-centre study
      was conducted prospectively in 22 hospitals across Thailand in 2015. The
      occurrences of perioperative adverse events were collected. The data was collated
      by site manager and forwarded to the data management unit. All perioperative
      convulsion incidences were enrolled and analysed. The consensus was documented
      for the relevant factors and the corrective strategies. Descriptive statistics
      were used. From 2,000 incident reports, perioperative convulsions were found in
      16 patients. Six episodes (37.5%) were related to anaesthesia, 31.3% to patients,
      18.8% to surgery, and 12.5% to systemic processes. The contributing factor was an
      inexperienced anaesthesia performer (25%), while the corrective strategy was
      improvements to supervision (43.8%). Incidents of perioperative convulsion were
      found to be higher than during the last decade. The initiation and maintenance of
      safe anaesthesia should be continued.

PMID- 29633916
TI  - Discovery of novel estrogen-related receptor alpha inverse agonists by virtual
      screening and biological evaluation.

PMID- 29633917
TI  - Multiple e-Pharmacophore modeling to identify a single molecule that could target
      both streptomycin and paromomycin binding sites for 30S ribosomal subunit
      inhibition.
AB  - The bacterial ribosome is an established target for anti-bacterial therapy since
      decades. Several inhibitors have already been developed targeting both defined
      subunits (50S and 30S) of the ribosome. Aminoglycosides and tetracyclines are two
      classes of antibiotics that bind to the 30S ribosomal subunit. These inhibitors
      can target multiple active sites on ribosome that have a complex structure. To
      screen putative inhibitors against 30S subunit of the ribosome, the crystal
      structures in complex with various known inhibitors were analyzed using
      pharmacophore modeling approach. Multiple active sites were considered for
      building energy-based three-dimensional (3D) pharmacophore models. The generated
      models were validated using enrichment factor on decoy data-set. Virtual
      screening was performed using the developed 3D pharmacophore models and molecular
      interaction towards the 30S ribosomal unit was analyzed using the hits obtained
      for each pharmacophore model. The hits that were common to both streptomycin and
      paromomycin binding sites were identified. Further, to predict the activity of
      these hits a robust 2D-QSAR model with good predictive ability was developed
      using 16 streptomycin analogs. Hence, the developed models were able to identify
      novel inhibitors that are capable of binding to multiple active sites present on
      30S ribosomal subunit.

PMID- 29633918
TI  - A novel device for preoperative skin preparation to reduce the risk of injury and
      surgical site infection during lower limb surgery.
AB  - Surgical site infection (SSI) continues to be a feared complication of surgery
      but especially orthopaedic surgery where a superficial SSI has been estimated to
      add nine days to the hospital stay and an average of L2500 to the cost. Despite
      the efficacy of all skin preparation agents being maximal at around 10 minutes no
      current system, apart from the double prep method attributed to Sir John
      Charnley, allows adequate control of bacteria. Current techniques of skin
      preparation require lifting of the limb with an associated risk of injury to
      theatre operatives. In order to provide for longer duration of contact,
      potentially better antisepsis and to remove the dangers inherent in lifting the
      limb we developed a novel system for limb antisepsis prior to surgery. To
      demonstrate efficacy we performed a single blind randomised controlled trial
      powered to demonstrate non-inferiority. We demonstrated a significant benefit of
      the device in terms of bactericidal effect. Whilst only recently entering full
      production, we would recommend the system as a significant improvement over
      current techniques of limb antisepsis.

PMID- 29633919
TI  - Computational study of the binding mechanism between farnesoid X receptor alpha
      and antagonist N-benzyl-N-(3-(tertbutyl)-4-hydroxyphenyl)-2,6-dichloro-4
      (dimethylamino) benzamide.
AB  - Farnesoid X receptor alpha (FXRalpha) is a bile acid-activated transcription
      factor, which plays important roles in the regulation of multiple metabolic
      processes. Development of FXR antagonist has revealed great potential for the
      treatment of metabolic disorders. The compound N-Benzyl-N-(3-(tertbutyl)-4
      hydroxyphenyl)-2,6-dichloro-4-(dimethylamino). Benzamide (NDB) was recently
      determined as a selective antagonist of FXRalpha, while the detailed interaction
      mechanism is not well understood. In this study, the combined computational
      methods including molecular dynamics simulations, binding free energy
      calculation, and principal component analysis were utilized to investigate the
      effect of NDB on the dynamics behaviors and dimerization of FXRalpha The binding
      free energy calculation indicated that the protein dimerization increases NDB
      affinity and the binding of NDB also stabilizes the interaction between two
      subunits of FXRalpha. Further decomposition of the overall binding free energies
      into individual residues identifies several residues significant for NDB binding,
      including Leu291, Met294, Ala295, His298, Met332, Ser336, Ala452, and Leu455. It
      also suggests that the interactions of L289(A)-W458(B), W458(A)-L289(B), R459(A)
      N461(B), and N461(A)-R459(B) are important for the dimer stabilization. This
      study provides a molecular basis for the understanding of binding mechanism
      between antagonist NDB and FXRalpha and valuable information for the novel FXR
      modulators design for the treatment of metabolic syndrome.

PMID- 29633920
TI  - The tragedy of becoming tired of living: Youth and young adults' suicide in
      Greenland and Denmark.
AB  - BACKGROUND: Suicide is a tremendous public health issue and worldwide the second
      leading cause of death among young people. In 2015, Greenland had the highest
      burden of disease due to self-harm with loss of 2,952.97 disability-adjusted life
      years per 100,000 inhabitants, more than six times as many as Denmark. AIMS: What
      are possible reasons for Greenland's higher youth suicide rate compared to
      Denmark, despite being one kingdom of Denmark? METHOD: Mixed methods in the form
      of qualitative, semi-structured interviews, the analysis of available data for
      2003-2016 and a literature review were conducted with the aim to answer this
      question. RESULTS: Several exposures cause this difference, most significantly
      adverse effects of the colonial past, such as social issues and experienced
      traumas in Greenland compared to its former coloniser Denmark. CONCLUSION: The
      ongoing burden of youth suicide in Greenland requires enhanced actions of all
      stakeholders involved in suicide prevention, intervention and postvention.

PMID- 29633923
TI  - Improvements in Tritrichomonas foetus molecular testing.
AB  - Bovine trichomoniasis is a sexually transmitted disease that results in
      infertility, abortion, and calf age variability. To date, management strategies
      include testing for Tritrichomonas foetus and culling of infected males.
      Challenges associated with testing include cost of culture medium, time and labor
      burden of sample incubation and processing, and adverse effects of bacterial
      growth on detection sensitivity. To overcome these challenges, we developed a
      direct reverse-transcription quantitative real-time PCR (direct RT-qPCR)
      utilizing smegma, eliminating the use of culture medium. In an analysis of 166
      field samples (56 positives and 110 negatives as determined using microscopic
      reading of cultures as the reference test), the direct RT-qPCR exhibited 100%
      diagnostic sensitivity and 100% specificity, whereas the currently employed qPCR
      (culture qPCR), which utilizes cultured samples, exhibited 95% diagnostic
      sensitivity and 100% specificity. Agreement between direct RT-qPCR and culture
      qPCR was 98%. Moreover, direct RT-qPCR identified 3 more positive samples and
      exhibited lower quantification cycle (Cq) values among positives by culture
      reading than did culture qPCR (direct RT-qPCR Cq range = 14.6-32.3 vs. culture
      qPCR Cq range = 18.7-37.4). The direct RT-qPCR enables simplified sample
      collection, elimination of culture medium, faster results, applicability in cows,
      and lower cost than culture qPCR.

PMID- 29633924
TI  - Occlusive Hepatic Artery Thrombus in a Deceased-Donor Liver Procured From a Donor
      With Blunt Abdominal Trauma Following a Road Traffic Collision Accident.
AB  - Here, we describe a case of occlusive hepatic artery thrombus in a liver procured
      from an 18-year-old deceased donor after circulatory death. The donor had died of
      multiple trauma following a road traffic collision. Occlusive thrombus was found
      at the hepatic artery bifurcation during back-table preparation. Consequently,
      the liver transplant did not proceed. We suggest careful assessment of hepatic
      arteries of all donor livers before transplant, particularly those from donors
      who are involved in deceleration injuries. Transplanting such livers may lead to
      primary nonfunction.

PMID- 29633922
TI  - Recent advances in magnetic resonance imaging for peripheral artery disease.
AB  - The global burden of peripheral artery disease (PAD) is significant. This has led
      to numerous recent advances in magnetic resonance imaging (MRI) techniques in
      PAD. Older techniques such as time of flight MRI or phase contrast MRI are
      burdened by long acquisition times and significant issues with artifacts. In
      addition, the most used MRI modality, contrast-enhanced MR angiography (CE-MRA)
      is limited by the use of gadolinium contrast and its potential toxicity. Novel
      MRI techniques such as arterial spin labeling (ASL), blood-oxygen-level dependent
      imaging (BOLD), and first-pass perfusion gadolinium enhancement are advancing the
      field by providing skeletal muscle perfusion/oxygenation data while maintaining
      excellent spatial and temporal resolution. Perfusion data can be critical to
      providing objective clinical data of a visualized stenosis. In addition, there
      are a number of new MRI sequences assessing plaque composition and lesion
      severity in the absence of contrast. These approaches used in combination can
      provide useful clinical and prognostic data and provide critical endpoints in PAD
      research.

PMID- 29633925
TI  - A Rare Case of Calciphylaxis in an Orthotopic Liver Transplant Recipient with
      Acute Kidney Injury.
AB  - Calciphylaxis is a rare disease characterized by calcification of small- to
      medium-sized blood vessels in the dermis and subcutaneous fat, resulting in
      cutaneous necrosis. Although most commonly shown in patients with end-stage
      kidney disease, it has also been reported in patients with other diseases,
      including alcoholic cirrhosis and malignancies. Here, we report an unusual case
      of calciphylaxis in an orthotopic liver transplant recipient with acute kidney
      injury. The patient, a 43-year-old white female with a history of type 2 diabetes
      mellitus, alcoholic cirrhosis, and normal kidney function, presented with
      decompensated liver disease and hepatorenal syndrome; she no longer responded to
      medical treatment and required treatment with dialysis. Ten days after admission,
      she underwent liver transplant, resulting in improved liver function tests. She
      had acute tubular necrosis (creatinine peak: 325 MUmol/L) from sustained
      hypotension during and after surgery, which required 4 sessions of dialysis over
      2weeks. Six weeks after her transplant, she developed painful, nonulcerating,
      erythematous plaques over her shins and thighs. Skin biopsy of the lesions showed
      calciphylaxis, calcium deposits, and thrombotic vasculopathy. She also developed
      severe hypercalcemia (calcium level of 2.75 mmol/L) from immobility, which
      required treatment with a bisphosphonate and hemodialysis. The lesions improved 6
      weeks later, and her renal function returned to normal. Calciphylaxis diagnosed
      in an orthotopic liver transplant recipient with acute kidney injury has not been
      previously reported. We hypothesize that her chronic inflammatory state caused
      down-regulation and low levels of fetuin A and protein C. She also had other risk
      factors, including hypoalbuminemia, obesity, systemic glucocorticoids, and
      alcoholic liver disease. Calciphylaxis can occur in patients with alcoholic
      cirrhosis and acute renal failure even after liver transplant. Further studies
      into the pathogenesis of this disease may help us understand why it develops in
      these patients and not others with the same risk factors.

PMID- 29633926
TI  - Alemtuzumab Induction Reduces Early Rejection in Female Renal Allograft
      Recipients: A Single Center Study.
AB  - OBJECTIVES: Previous research studies have highlighted differences in rejection
      and graft survival across sexes that favor men. We compared delayed graft
      function, rejection, graft survival, and overall patient survival between sexes
      following alemtuzumab induction. MATERIALS AND METHODS: After Internal Review
      Board approval, a retrospective analysis of kidney transplants completed at the
      University of Toledo Medical Center between March 2004 and November 2015 was
      conducted. RESULTS: During the study period, 675 transplants were performed. This
      included 429 male patients (63.6%) and 246 female patients (36.4%). Recipient sex
      was not associated with delayed graft function. Acute rejection occurred less
      frequently in women than in men at 3 months (12.6% vs 20.7%; P = .009) and at 6
      months (15.9% vs 24.6%; P = .008). Cumulative patient survival was superior in
      women (P = .032). Female recipient death-censored graft survival was inferior at
      3 years (85.4% vs 91.6%; P = .034) and at 5 years (77.7% vs 86.9%; P = .019)
      versus male patients. CONCLUSIONS: Compared with men, early female rejection is
      reduced and overall female survival is longer after alemtuzumab induction.
      However, intermediate-term female graft survival is less.

PMID- 29633927
TI  - Psychiatric Evaluation of Children During the Organ Transplant Process.
AB  - OBJECTIVES: Organ transplantation is performed frequently in Turkey. A routine
      psychiatric examination is performed before all transplant procedures, and
      psychiatric support is continued during the posttransplant period. In this study,
      we reviewed the psychiatric consultation records of child and adolescent patients
      admitted to Baskent University Hospital who underwent or were scheduled to
      undergo transplant to determine the prevalence of psychiatric disorders in this
      population. MATERIALS AND METHODS: Fifty-nine transplant patients were seen by
      the Department of Child and Adolescent Psychiatry between 2012 and 2015 and were
      evaluated based on the Diagnostic and Statistical Manual of Mental Disorders, 4th
      Edition. RESULTS: Thirty patients (50.8%) were female, and 29 patients (49.2%)
      were male. The mean age of the study population was 10.2 +/- 4.5 years, and the
      mean age at transplant was 9.9 +/- 4.6 years. In total, 69.5% of participants
      were diagnosed with a psychiatric disorder. The most common diagnosis was
      adjustment disorder, with a prevalence of 52.4%. CONCLUSIONS: Our study found
      that psychiatric disorders are frequently encountered in pediatric transplant
      patients. This study revealed a higher prevalence of psychiatric disorders during
      the posttransplant period than during the pretransplant period.

PMID- 29633928
TI  - Living-Donor Liver Transplant for Fibrolamellar Hepatocellular Carcinoma With
      Hilar Lymph Node Metastasis: A Case Report.
AB  - Fibrolamellar hepatocellular carcinoma is a rare primary malignant liver
      neoplasm. Benefits from liver transplant for patients with fibrolamellar
      hepatocellular carcinoma have not yet been reported. Here, we report a 19-year
      old female patient who presented with abdominal pain. A computed tomography scan
      revealed bilobar and multiple solid lesions with the largest measuring 15 cm in
      diameter on the right lobe of her liver. Her blood alpha-fetoprotein level and
      viral hepatitis markers were normal. A fine-needle biopsy of the largest lesion
      detected fibrolamellar heptocellular carcinoma. Because no distant metastasis was
      evident and the carcinoma was unresectable, a right lobe living-donor liver
      transplant with hilar lymph node dissection was performed. A pathology report
      revealed poorly differentiated fibrolamellar hepatocellular carcinoma, and
      further testing indicated microvascular invasion and hilar lymph node metastasis.
      The largest tumor measured 12 cm. She was discharged on postoperative day 14.
      During postoperative month 22, multiple vertebral metastases were detected, and
      she died with diffuse metastasis during postoperative month 26. Our patient, with
      poor prognostic criteria such as hilar lymph node metastasis, microvascular
      invasion, and poor differentiation, had 22 months of tumor-free survival and 26
      months of overall survival after having undergone living-donor liver transplant.

PMID- 29633929
TI  - Liver Regeneration-Related Cytokine Profiles in Donors and Recipients Before and
      After Living-Donor Liver Transplant.
AB  - OBJECTIVES: The liver's capability to completely regenerate after injury is a
      unique phenomenon in which cytokines are of particular interest. Here, we aimed
      to assess the release patterns and prognostic relevance of liver regeneration
      related cytokines in the setting of living-donor liver transplant. MATERIALS AND
      METHODS: Eleven cytokines related to liver regeneration (hepatocyte growth
      factor, interleukin 6, insulin-like growth factor-1, tumor necrosis factor alpha,
      transforming growth factor beta, granulocyte colony-stimulating factor, stem cell
      factor, chemokine (C-X-C motif) ligand 12, angiogenin, fibroblast growth factor
      2, and vascular endothelial growth factor) were compared in 13 living-donor liver
      transplant recipients and their corresponding donors before and daily (10 days)
      after transplant. Patients and donors were stratified by clinical outcomes (early
      graft loss within 4 weeks after transplant vs beneficial outcome). RESULTS: Most
      cytokines tested (especially tumor necrosis factor alpha and stem cell factor)
      were elevated in recipients versus donors. Many cytokines were also increased in
      recipients with graft loss (especially CXCL12) and in donors of recipients with
      beneficial outcomes (especially fibroblast growth factor 2). Fibroblast growth
      factor 2 levels were also correlated positively with serum gamma
      glutamyltransferase, and higher preoperative concentrations in donors were
      associated with recipients having beneficial outcomes, indicating an improved
      regenerative capacity. In contrast, elevated CXCL12 levels in recipients before
      and after LDLT predicted graft loss and were linked to ongoing liver damage.
      CONCLUSIONS: In living-donor liver transplant, there are distinct differences
      between donors and recipients regarding the release of liver regeneration-related
      cytokines. Moreover, fibroblast growth factor 2 and CXCL12 may be of diagnostic
      value in a complementary way to describe or even predict the possible outcomes
      after transplant. These results may be of clinical interest not only for living
      donor liver transplant but also for acute liver failure.

PMID- 29633931
TI  - Autologous Hematopoietic Stem Cell Transplantation for Antiphospholipid Syndrome:
      Case Report and Review of the Literature.
AB  - Refractory antiphospholipid syndrome represents a challenge for preventing
      thrombosis that may occur despite adequate anticoagulation and immunomodulation
      therapy. Here, we report a 35-year-old male patient who presented with variable
      venous thromboembolic events. Autologous hematopoietic stem cell transplant was
      performed after conditioning with cyclophosphamide and antithymocyte globulin.
      Five years after transplant, the treatment continued to show a successful outcome
      in preventing new thrombotic events. Autologous hematopoietic stem cell
      transplant represents a chance for cure from antiphospholipid syndrome despite
      the paucity of reported data so far.

PMID- 29633930
TI  - Clinical Significance of Pulmonary Nodules in the Pretransplant Evaluation of
      Liver Transplant Recipients With Hepatocellular Carcinoma.
AB  - OBJECTIVES: Pulmonary nodules are common in patients with hepatocellular
      carcinoma who are being evaluated for a possible liver transplant. MATERIALS AND
      METHODS: In this retrospective study, we analyzed the records of liver transplant
      recipients at our institution with a primary diagnosis of hepatocellular
      carcinoma who received transplants between 2000 and 2015. All patients had
      magnetic resonance imaging-confirmed disease within Milan criteria and a
      concurrent staging chest computed tomography. Patient survival was estimated
      using Kaplan-Meier methods and compared between pulmonary nodule characteristic
      groups. A Cox proportional hazards model was constructed for adjusted analysis.
      RESULTS: Of the 197 liver transplant recipients who met our study inclusion
      criteria (median follow-up, 40 mo), 115 (58.4%) had a total of 231 pulmonary
      nodules, with 57 (49.6%) having multiple nodules and 108 (93.9%) having nodules
      <= 1 cm. The presence of pulmonary nodules did not negatively affect patient
      survival, per our univariate and multivariate analysis, nor did their presence
      affect their number, location, laterality, shape, edge, density, or the presence
      of calcifications (P >=.05). However, pulmonary nodules >= 1 cm were associated
      with decreased overall survival. CONCLUSIONS: In our pretransplant evaluation of
      patients with hepatocellular carcinoma, pulmonary nodules <= 1 cm did not portend
      worse patient or graft survival posttransplant.

PMID- 29633932
TI  - Tacrolimus-Induced Autoimmune Hemolytic Anemia in a Previously Reported Child
      With History of Thrombocytopenia Following Liver Transplant.

PMID- 29633933
TI  - Successful Repair of Bilateral Ureteral Stricture 3 Years after En Bloc Kidney
      Transplant: A Case Report.
AB  - En bloc kidney transplants of small pediatric kidneys into adult recipients have
      been shown to have outcomes similar to transplants from standard adult deceased
      donors. Here, we report a 27-year-old male patient with successful repair of
      bilateral ureteral stricture 3 years after en bloc kidney transplant at the
      Shahid Modarres Hospital (Tehran, Iran). The patient received an en bloc deceased
      kidney donation from a 9-month-old infant. An end-to-end anastomosis of the aorta
      to the internal iliac artery and an end-to-side external iliac vein anastomosis
      to vena cava were performed. At an outpatient visit about 2.5 years later, the
      patient showed increasing levels of creatinine from 1.1 to 1.8 mg/dL compared
      with measurements at his 2-month visit. A computed tomography scan performed
      without any contrast agent at that time confirmed the existence of hydronephrosis
      in both the medial and lateral kidneys. A nephrostography showed a ureteral
      stricture. Because endoscopic surgery for ureteral dilatation was not successful,
      the decision was made to perform ureteral repair by the open surgical technique.
      The short length of the ureters resulted in the lateral renal pelvis being
      anastomosed to the bladder by flap (Boari flap). The ureter of the patient's
      native kidney was transected in the middle portion, and the distal ureter was
      anastomosed to the medial renal pelvis using the end-to-end method. Here, we
      showed that, despite limited experiences with pediatric donors, en bloc kidney
      transplant can be performed under the guidance of experienced surgical techniques
      and precise postoperative follow-up.

PMID- 29633934
TI  - Antibacterial activity and mode of action of epsilon-polylysine against
      Escherichia coli O157:H7.
AB  - PURPOSE: Gram-negative Escherichia coli O157:H7 were chosen as model bacteria to
      evaluate the antimicrobial mechanism of epsilon-polylysine (epsilon-PL).
      METHODOLOGY: The antibacterial activity of epsilon-PL was detected by measuring
      the minimum inhibitory concentration values as well as the time-kill curve. The
      membrane integrity was determined by ultraviolet (UV) absorption, membrane
      potential (MP) assay and flow cytometry (FCM) experiments. The permeability of
      the inner membrane was detected by beta-galactosidase activity assay.
      Furthermore, electron microscopy [scanning electron microscopy (SEM) and
      transmission electron microscopy (TEM)] was utilized to observe bacterial
      morphology. KEY FINDINGS: These results demonstrated that epsilon-PL showed its
      antibacterial activity by changing the integrity and permeability of cell
      membranes, leading to rapid cell death. The electron microscopy analysis (SEM and
      TEM) results indicated that the bacterial cell morphology, membrane integrity and
      permeability were spoiled when the E. coli O157:H7 cells were exposed to minimum
      inhibitory concentrations of epsilon-PL (16 ug ml-1). In addition, the bacterial
      membrane was damaged more severely when the concentration of epsilon-PL was
      increased. CONCLUSION: The present study investigated the antimicrobial mechanism
      of epsilon-PL by measuring the content of cytoplasmic beta-galactosidase,
      proteins and DNA. In addition, SEM and TEM were carried out to assess the
      mechanism. These results show that epsilon-PL has the ability to decrease the
      content of large molecules, cellular soluble proteins and nucleic acids
      associated with increasing the content of cytoplasmic beta-galactosidase in
      supernatant by causing damage to the cell membranes. Consequently, the use of
      epsilon-PL as a natural antimicrobial agent should eventually become an appealing
      method in the field of food preservation.

PMID- 29633935
TI  - Correlation between bacterial G+C content, genome size and the G+C content of
      associated plasmids and bacteriophages.
AB  - Based on complete bacterial genome sequence data, we demonstrate a correlation
      between bacterial chromosome length and the G+C content of the genome, with
      longer genomes having higher G+C contents. The correlation value decreases at
      shorter genome sizes, where there is a wider spread of G+C values. However,
      although significant (P<0.001), the correlation value (Pearson R=0.58) suggests
      that other factors also have a significant influence. A similar pattern was seen
      for plasmids; longer plasmids had higher G+C values, although the large number of
      shorter plasmids had a wide spread of G+C values. There was also a significant
      (P<0.0001) correlation between the G+C content of plasmids and the G+C content of
      their bacterial host. Conversely, the G+C content of bacteriophages tended to
      reduce with larger genome sizes, and although there was a correlation between
      host genome G+C content and that of the bacteriophage, it was not as strong as
      that seen between plasmids and their hosts.

PMID- 29633936
TI  - Chitin-induced T6SS in Vibrio cholerae is dependent on ChiS activation.
AB  - Vibrio cholerae regularly colonizes the chitinous exoskeleton of crustacean
      shells in the aquatic region. The type 6 secretion system (T6SS) in V. cholerae
      is an interbacterial killing device. This system is thought to provide a
      competitive advantage to V. cholerae in a polymicrobial community of the aquatic
      region under nutrient-poor conditions. V. cholerae chitin sensing is known to be
      initiated by the activation of a two-component sensor histidine kinase ChiS in
      the presence of GlcNAc2 (N,N'-diacetylchitobiose) residues generated by the
      action of chitinases on chitin. It is known that T6SS in V. cholerae is generally
      induced by chitin. However, the effect of ChiS activation on T6SS is unknown.
      Here, we found that ChiS inactivation resulted in impaired bacterial killing and
      reduced expression of T6SS genes. Active ChiS positively affected T6SS-mediated
      natural transformation in V. cholerae. ChiS depletion or inactivation also
      resulted in reduced colonization on insoluble chitin surfaces. Therefore, we have
      shown that V. cholerae colonization on chitinous surfaces activates ChiS, which
      promotes T6SS-dependent bacterial killing and horizontal gene transfer. We also
      highlight the importance of chitinases in T6SS upregulation.

PMID- 29633937
TI  - Incidence and predictors of acute kidney injury in patients undergoing proximal
      protected carotid artery stenting.
AB  - AIMS: Many studies have analysed the occurrence of acute kidney injury (AKI)
      after percutaneous coronary intervention (PCI) but there are limited data
      relating to AKI risk in patients undergoing carotid artery stenting (CAS). The
      aim of this study was to determine the incidence and predictors of AKI in
      patients undergoing proximal protected CAS. METHODS AND RESULTS: We analysed 456
      patients undergoing proximal protected CAS. A binomial multivariate logistic
      model was developed including patients' clinical and angiographic/procedural
      characteristics. AKI (defined as an sCr increase >=0.3 mg/dl or >=1.5-fold sCr
      increase from baseline or more than 50% increase from baseline, within 48 hours
      post procedure) occurred in 155 patients (34%). AKI patients were more frequently
      affected by hypertension, diabetes, dyslipidaemia and anaemia, and presented
      lower renal function at baseline. Higher contrast volume to creatinine clearance
      ratio (2.40+/-1.44 vs. 2.08+/-1.15; p=0.01), lower post-procedural mean arterial
      pressure (MAP) (94.3+/-17.7 vs. 99.6+/-18.5 mmHg; p=0.003) and a more frequent
      post-procedural systolic pressure drop (?SBP >50 mmHg) (23.9% vs. 14.3%, p=0.01)
      were observed in the AKI group of patients. At multivariate analysis, independent
      predictors of AKI were ?SBP >50 mmHg, diabetes mellitus and dyslipidaemia.
      CONCLUSIONS: AKI can occur quite frequently after proximal protected CAS and is
      related to clinical and procedural features. These data should be confirmed in
      larger registries or randomised trials.

PMID- 29633938
TI  - First experience with the 34 mm self-expanding Evolut R in a multicentre
      registry.

PMID- 29633939
TI  - Renal artery anatomy assessed by quantitative analysis of selective renal
      angiography in 1,000 patients with hypertension.
AB  - AIMS: With increasing attention to renovascular causes and targets for
      hypertension there arises a critical need for more detailed knowledge of renal
      arterial anatomy. However, a standardised nomenclature is lacking. The present
      study sought to develop a standardised nomenclature for renal anatomy considering
      the complexity and variation of the renal arterial tree and to assess the
      applicability of the nomenclature. METHODS AND RESULTS: One thousand hypertensive
      patients underwent invasive selective renal artery angiography in nine centres.
      Further, renovasography was performed in 249 healthy swine as a surrogate for
      normotensive anatomy. Anatomical parameters were assessed by quantitative
      vascular analysis. Patients' mean blood pressure was 168/90+/-26/17 mmHg. The
      right main renal artery was longer than the left (41+/-15 mm vs. 35+/-13 mm,
      p<0.001), but the left had a greater diameter (5.4+/-1.2 vs. 5.2+/-1.2 mm,
      p<0.001). Accessory renal arteries and renal artery disease were documented in
      22% and 9% of the patients, respectively. Other than exhibiting a longer left
      main renal artery in uncontrolled hypertensives (+2.7 mm, p=0.034) there was no
      anatomical difference between patients with controlled and uncontrolled
      hypertension. Main renal artery mean diameter was smaller in patients with
      impaired kidney function (GFR <90 ml/min, left -0.5 mm, right -0.4 mm, both
      p<0.001). CONCLUSIONS: Renal arterial anatomy differs between sides but shows no
      difference between patients with and without blood pressure control. Impaired GFR
      was associated with small main renal artery diameter.

PMID- 29633940
TI  - Long-term consequences of optical coherence tomography findings during
      percutaneous coronary intervention: the Centro Per La Lotta Contro L'infarto -
      Optimization Of Percutaneous Coronary Intervention (CLI-OPCI) LATE study.
AB  - AIMS: The role of intraprocedural optical coherence tomography (OCT) on the long
      term clinical outcome of percutaneous coronary interventions (PCI) remains
      undefined. The aim of the present study was to evaluate the impact of
      quantitative OCT-defined suboptimal stent implantation at long-term follow-up.
      METHODS AND RESULTS: In the context of the multicentre Centro per la Lotta contro
      l'Infarto - Optimisation of Percutaneous Coronary Intervention (CLI-OPCI)
      registry, we compared the long-term PCI outcome of 1,211 patients from 13
      independent OCT-experienced centres according to end-procedural OCT findings. OCT
      assessment revealed suboptimal stent implantation in 30.9% of lesions, with an
      increased prevalence in patients experiencing device-oriented cardiovascular
      events (DoCE) (52.8% vs. 28.0%, p<0.001). At a median follow-up of 833
      (interquartile range 415-1,447) days, in-stent minimum lumen area (MLA) <4.5 mm2
      (HR 1.82, p<0.001), distal stent edge dissection >200 um (HR 2.03, p=0.004), and
      significant reference vessel plaque and lumen area <4.5 mm2 at either the distal
      (HR 5.22, p<0.001) or proximal (HR 5.67, p<0.001) stent edges were independent
      predictors of device failure. Conversely, in-stent MLA/mean reference lumen area
      <70%, acute stent malapposition, and intra-stent plaque/thrombus protrusion were
      not associated with worse outcomes. Using multivariable Cox hazard analysis, the
      presence of at least one of the significant criteria for suboptimal OCT stent
      deployment was confirmed as an independent predictor of DoCE (HR 1.92, p=0.001).
      CONCLUSIONS: Suboptimal stent deployment, defined according to specific
      quantitative OCT criteria, was confirmed as an independent outcome predictor at
      long-term follow-up.

PMID- 29633941
TI  - Transcatheter treatment of tricuspid regurgitation using edge-to-edge repair:
      procedural results, clinical implications and predictors of success.
AB  - AIMS: The aim of this study was to analyse the feasibility, safety and
      effectiveness of tricuspid valve (TV) repair using the MitraClip system in
      patients at high surgical risk. METHODS AND RESULTS: Forty-two elderly high-risk
      patients (76.8+/-7.3 years, EuroSCORE II 8.1+/-5.7) with isolated TR or combined
      TR and mitral regurgitation (MR) underwent edge-to-edge repair of the TV (n=11)
      or combined edge-to-edge repair of the TV and mitral valve (n=31). Procedural
      details, success rate, impact on TR severity and predictors of success at 30-day
      follow-up were analysed. Successful edge-to-edge repair of TR was achieved in
      35/42 patients (83%, 68 clips in total, 94% in the anteroseptal commissure, 6% in
      the posteroseptal commissure). In five patients, grasping of the leaflets was
      impossible and two patients had no decrease in TR after clipping. In those with
      procedural success, clipping of the TV led to a reduction in effective
      regurgitant orifice area by -62.5% (from 0.8+/-0.4 to 0.3+/-0.2 cm2; p<0.0001).
      In both patients with isolated TV and combined procedures, six-minute walking
      distance improved (from 285+/-118 to 344+/-81 m and from 225+/-113 to 261+/-130
      m, p=0.02 and 0.03, respectively). Predominant anteroseptal or central TR was
      identified as a predictor of procedural success (p=0.025). CONCLUSIONS: Edge-to
      edge repair of the TV is feasible with a promising reduction in TR, which could
      result in clinical improvement.

PMID- 29633942
TI  - [New conceptual framework in advanced prostate cancer.]

PMID- 29633943
TI  - [Locally advanced prostate cancer. Definition, diagnosis and treatment.]
AB  - : Prostate cancer is a disease that presents a wide spectrum from low
      aggressiveness localized to disseminated cancer. Locally advanced prostate cancer
      (LAPC) is a particularly difficult to manage phase of this spectrum. OBJECTIVES:
      We review the definition, diagnosis and treatment of this phase of the disease.
      METHODS: We performed a non systematic literature review of the most relevant
      features of this pathology. RESULTS: LAPC is more aggressive than organ confined
      disease. Its clinical diagnosis is not always easy. Local treatment, in spite of
      being aggressive with potential sequelae, seems to be advantageous in terms of
      patient survival. CONCLUSIONS: Prostate cancer local staging is currently based
      on multiparametric magnetic resonance imaging (mpMRI). Local radical treatment
      with surgery or radiotherapy, with probable addition of systemic treatment,
      offers promising results for disease control and quality of life improvement.

PMID- 29633944
TI  - [Oligometastatic prostate cancer. concept and implications.]
AB  - Oligometastatic prostate cancer has been proposed as an intermediate stage
      between localized and extensively disseminated disease. Oligometastatic disease
      is being diagnosed more frequently due to the advances in imaging tests.
      Nevertheless, there is no consensus definition yet of oligometastatic prostate
      cancer. The importance of this entity is that several studies have pointed out
      that local and metastasis directed treatment may improve survival in selected
      patients. However, we need the results of well controlled prospective randomized
      clinical trials to help a better understanding and management of oligometastatic
      prostate cancer.

PMID- 29633945
TI  - [Current status of androgen deprivation therapy in hormone-sensitive prostate
      cancer.]
AB  - OBJECTIVE: To analyze the current available evidence of androgen deprivation
      therapy in hormone-sensitive metastatic prostate cancer, focused on the relevance
      of suppressing circulating testosterone levels and its prognostic significance.
      To assess the optimal value of castration levels and PSA reduction under hormone
      treatment. METHODS: We performed a bibliographic review through automatized
      search in the Pubmed bibliographic database and Clinical Key. The search strategy
      included the following terms: "prostate cancer" AND "hormones", "metastatic
      prostate cancer", "testosterone" AND "prostate cancer", "hormone naive/sensitive"
      AND "prostate cancer". RESULTS: Lower testosterone levels are associated with
      better survival and have prognostic significance. Values below 32-20 ng/dl, in
      accordance to different reported studies, have been established as optimal
      castration levels with clinical significance, with impact on cancer specific
      survival and time to castration resistance. Similarly, low PSA levels after
      starting hormone therapy have been suggested as a strong predictor of survival
      and treatment response. CONCLUSIONS: Close monitoring of PSA and testosterone
      levels is necessary in patients with metastatic prostate cancer during hormone
      deprivation treatment. Combination of both values allows to predict treatment
      response and early identification of tumor progression, and to put forward
      subsequent therapeutic strategies improving survival in this group of patients.

PMID- 29633946
TI  - [Preventive management of bone disease in advanced prostate cancer.]
AB  - OBJECTIVES: Prostate cancer is linked to bone disease by two different entities.
      On one hand, androgen deprivation therapy (ADT) usually causes osteoporosis, on
      the other a great number of patients with advanced prostate cancer will present
      bone that condition not only their vital prognosis but also an important quality
      of life deterioration. METHODS: We performed a bibliographic review on both the
      physiology and therapy of osteoporosis secondary to ADT and bone metastasis in
      prostatic neoplasias. RESULTS: Osteoporosis: Long term ADT is associated with
      osteopenia/osteoporosis in 80% of the patients, with a 5-20% incidence of
      osteoporotic fractures. We should monitor bone mineral density before starting
      ADT therapy and during treatment. Treatment is based on risk factors reduction,
      regular physical exercise, calcium and vitamin D supplements, and drugs such as
      biphosphonates or denosumab. Bone metastasis: Currently, both zolendronic acid
      and denosumab have approval for the prevention of skeletal events in patients
      with castration resistant prostate cancer (CPRC). Although the last one seems to
      be more effective, it is associated with a higher risk of hypocalcemia and jaw
      osteonecrosis so that the choice of drug must be individualized in every patient.
      The duration of treatment is not clear. Currently, the indication for the use of
      this drugs in earlier phases of advanced disease is not approved. CONCLUSIONS:
      Comprehensive management of the patient with advanced prostate cancer should
      include the study and treatment of osteoporosis and bone metastases. Currently,
      very effective therapies are available for both entities.

PMID- 29633947
TI  - [Maximal androgen deprivation with abiraterone acetate in hormone sensitive
      prostate cancer.]
AB  - OBJECTIVES: The treatment of metastatic prostate cancer has remained unchanged
      for more than 70 years, based on androgen deprivation therapy (ADT). In 2015,
      following the CHAARTED and STAMPEDE trials, it was established that the addition
      of 6 cycles of docetaxel to ADT was associated with significantly increased
      survival. In June 2017, the LATITUDE trial and the G arm of the STAMPEDE trial
      showed that the addition of Abiraterone with Prednisone (5 mg/day) to ADT was
      also associated with a significant increase in survival in metastatic patients.
      The present study analyzes these two trials. RESULTS: LATITUDE demonstrated a 38%
      reduction in the risk of death (HR=0.62, 95% CI, 0.61-0.76) in almost all sub
      groups. Risk reduction for radiological progression was 53% (HR=0.47, 95% CI 0.39
      0.55). Secondary objectives such as prostate specific antigen progression, time
      to chemotherapy or a new skeletal event are also significantly delayed. STAMPEDE
      also showed that the combination of Abiraterone and Prednisone is associated with
      a 37% increase in survival (HR=0.63, 95% CI, 0.52- 0.76, p<0.001) in metastatic
      patients, but not in nonmetastatic patients. Progression-free survival was
      greatly improved in this arm (HR=0.29, 95% CI 0.25-0.34, p<0.001). The side
      effects reported show the known pattern of mineral corticosteroid excess with
      increased blood pressure, hypokalemia, and of liver enzymes elevation.
      CONCLUSIONS: The indirect comparison of docetaxel and abiraterone studies
      confirms that both populations and results are comparable. Two comparative
      indirect metanalysis (>6000 patients) gave marginal superiority to abiraterone.
      In favor of abiraterone we have that it is an oral, comfortable medication with a
      good tolerance profile and side effects that are easy to manage, useful in
      patients who are old and fragile, in whom chemotherapy may not be indicated; the
      downsides are prolonged exposure to the drug and its current price. Future
      trials, currently in progress, will determine the ideal patient profile, or a
      potential association of both therapies.

PMID- 29633948
TI  - [The role of chemotherapy in the treatment of hormone sensitive metastatic
      prostate cancer.]
AB  - OBJECTIVE: Several studies have assessed the role of adding chemotherapy to
      hormonal treatment for metastatic hormone-sensitive prostate cancer (MHSPC). The
      objective of this manuscript is to review these studies and to provide
      recommendations for the management of these patients. METHODS: We identified
      published clinical trials comparing hormone blockade (HB) with HB plus docetaxel
      as first-line treatment of HSMPC and we analyzed their results in terms of
      efficacy and toxicity. RESULTS: Of the 3 trials published, two demonstrated
      increased overall survival by adding docetaxel to the first-line treatment of
      MHSPC (CHAARTED and Stampede-Docetaxel studies) and the third one did not show
      such an advantage (GETUG-AFU15). In the CHAARTED study, the survival advantage
      was limited to patients presenting high tumor volume. Toxicity was increased in
      patients who received docetaxel. CONCLUSIONS: The addition of docetaxel to
      treatment with HB should be considered in patients with MHSPC, especially in
      those with high tumor volume. However, the toxicity and recent results of trials
      performed with abiraterone in MHSPC should also be taken in consideration.

PMID- 29633949
TI  - [The role of corticoids in the management of advanced prostate cancer.]
AB  - Prostate cancer is the most frequent malignant tumor in males in developed
      countries and represents the second cause of cancer death. Over the last years,
      the number of treatments available for patients with advanced prostate cancer has
      improved significantly, achieving better disease control and notably better
      overall survival (1). Corticosteroids have been extensively used in the treatment
      of castration resistant prostate cancer due to their palliative benefits on
      symptoms secondary to their potent anti-inflammatory activity and their
      demonstrated antitumor activity. At present time, we have a wide therapeutic
      arsenal for patients with metastatic prostate cancer and concomitant medication
      with corticosteroids may counteract adverse events of the main validated
      therapies. Nevertheless, long term exposition to corticosteroid treatment
      required by prostate cancer patients may have negative implications in terms of
      development of potential adverse events and, in certain cases, even facilitating
      disease progression.

PMID- 29633950
TI  - [Surgical treatment of local disease in metastatic prostate cancer.]
AB  - OBJECTIVES: Metastatic prostate cancer is a very heterogeneous disease with
      several treatment options. In some cases of oligometastatic disease, local
      treatment of the primary tumor complemented by metastasis directed therapy seems
      to improve oncological results. The objectives of this study are to define and
      understand oligometastatic prostate cancer, to show the usefulness and rationale
      of cytoreductive surgery in this scenario and to review all published studies
      about radical prostatectomy in patients with initially metastatic prostate
      cancer. METHODS: We performed a Pubmed bibliographic search using the keywords:
      prostate cancer, metastatic, oligometastatic, local treatment, radical
      prostatectomy, and cytoreductive surgery. We included all published works on
      radical prostatectomy in initially metastatic patient. Furthermore, we reviewed
      published articles about cytoreductive surgery and biology of the oligometastatic
      disease in journals of different medical specialties. RESULTS: Oligometastatic
      prostate cancer is recognized as an intermediate clinical stage between local and
      disseminated disease that seems to benefit from local treatment of the primary
      tumor plus metastasis directed treatment. In this scenario, different
      retrospective studies have demonstrated that radical prostatectomy diminishes
      local complication rate and improves oncological results without increasing
      morbidity. Currently, there is no consensus definition about the number,
      location, and imaging techniques to employ to consider a patient oligometastatic.
      Thus, it is difficult to compare the results of the different studies and
      identification of a subgroup of patients that could benefit from this local
      treatment. CONCLUSIONS: In absence of prospective randomized data, radical
      prostatectomy seems to be useful for local treatment of the primary tumor in a
      selected group of patients with oligometastatic prostate cancer.

PMID- 29633951
TI  - [Radiotherapy for local disease in metastatic prostate cancer.]
AB  - OBJECTIVES: We elaborate the bases and rationale for the application of
      multimodal extended treatment including local radiotherapy in patients with
      oligometastatic prostate cancer (omPCa). We performed a bibliographic review on
      the state of the art in this field and propose a therapeutic strategy that
      incorporates ablative radiotherapy of the primary tumor +/- oligometastatic
      lesions. METHODS: We performed a comprehensive literature review consulting
      different sources that include data bases (Pubmed/Medline), and international
      treatment guidelines ((NCCN, NCI, EUA). Search criteria: Locally advanced
      prostate cancer, oligometastatic, disseminated and radiotherapy, ablative or
      stereotactic radiotherapy (SBRT). RESULTS: The most accepted definition for
      oligometastatic prostate cancer or oligotopic prostatic neoplasia is when we
      recognize at least 3 non-visceral metastatic lesions in an extrapelvic location.
      Whole body MRI and PET scan (Choline/PSMA) are non conventional useful tests for
      staging in the workup for oligometastatic disease. From a clinical point of view,
      omPCa behaves as an intermediate entity between locally advanced and disseminated
      or multimetastatic prostate cancer. Androgen deprivation therapy (ADT) represents
      the base of treatment for castration sensitive PCa. To date there is no
      biological marker/genetic sign identified that differentiate aggressiveness
      profiles in omPca. Most evidence on the use of radiotherapy for this entity comes
      from retrospective studies, showing a benefit in control and prevention of local
      symptoms. To date, the survival benefit derived from the application of local
      treatment to the primary tumor with demonstrable metastatic disease is uncertain,
      and it has not been shown in the available randomized prospective clinical
      trials. CONCLUSIONS: Primary tumor radiotherapy in omPca positively influences
      local control and prevention of local symptoms progression. The level of evidence
      to recommend prostatic radiotherapy as a therapeutic variable with impact on
      survival on omPca is limited (Level 2B-3 Category). Research lines in omPca
      deserve the inclusion of a multimodal systemic treatment including ADT, ablative
      radiotherapy for the tumor and consolidation radiotherapy in metastatic distant
      lesions.

PMID- 29633952
TI  - [Advanced prostate cancer and quality of life.]
AB  - OBJECTIVES: The therapeutic range in advanced and castration resistant prostate
      cancer is widening. Therapies must offer real clinical efficacy, and they also
      should be acceptable and desirable for patients, specially in advanced disease.
      We analyze the value of quality of life analysis in patients with advanced
      prostate cancer. METHODS: We performed a bibliographic review (Pubmed) with the
      various health related quality of life scales available and different clinical
      trials on advanced prostate cancer. RESULTS: There are numerous therapeutic
      options but, due to variations in study design, a different evaluation of adverse
      events and different therapeutic regimens, comparisons are difficult. A common
      method to interpret results is not available, so most of the times that
      interpretation is left to statistical significance, which is not always well
      correlated with clinical significance. CONCLUSIONS: To propose the most adequate
      treatment in patient's interest, we need results focused on patients that combine
      not only quantity or overall survival but also quality of life. Parameters such
      as QALY should be included in clinical trials as evaluation objectives in order
      to favor decision taking.

PMID- 29633953
TI  - [Multidisciplinary teams in the treatment of prostate cancer.]
AB  - In the last decade, prostate cancer management has dramatically evolved to such a
      complexity that different medical specialties have to participate for its
      optimization, even making necessary in many cases super specialization in every
      discipline for such aim. All Guidelines and every Scientific Association do
      recommend multidisciplinary teams for its management as a rule, but translation
      from multidisciplinary committees to daily assistance is heterogeneous and faces,
      many times, particular interests and conflicts between different specialties
      implying that objective information of all the therapeutic options does not reach
      the patient to enroll him in his own therapeutic pathway.This is an opinion paper
      reviewing the advantages of the multidisciplinary team daily work as a
      prolongation of the multidisciplinary committee decisions, relying in the
      literature to set the legal framework and recommendations to generate an
      operative and real model of multidisciplinary teamwork for the benefit of both
      patient and all professionals involved in prostate cancer management.

PMID- 29633954
TI  - Investigation of indirect excitons in bulk 2H-MoS2 using transmission electron
      energy-loss spectroscopy.
AB  - We have investigated indirect excitons in bulk 2H-MoS2 using transmission
      electron energy-loss spectroscopy. The electron energy-loss spectra were measured
      for various momentum transfer values parallel to the [Formula: see text] and
      [Formula: see text] directions of the Brillouin zone. The results allowed the
      identification of the indirect excitons between the valence band K v and
      conduction band Lambdac points, the Gammav and K c points as well as adjacent K v
      and [Formula: see text] points. The energy-momentum dispersions for the K v
      Lambdac, Gammav-K c and K v1-[Formula: see text] excitons along the [Formula: see
      text] line are presented. The former two transitions exhibit a quadratic
      dispersion which allowed calculating their effective exciton masses based on the
      effective mass approximation. The K v1-[Formula: see text] transition follows a
      more linear dispersion relationship.

PMID- 29633955
TI  - Stable gelatin-based phantom materials with tunable x-ray attenuation properties
      and 3D printability for x-ray imaging.
AB  - We report a novel method for developing gelatin-based phantom materials for
      transmission x-ray imaging with high stability at room temperature and tunable x
      ray attenuation properties. This is achieved by efficiently cross-linking gelatin
      in a glycerin solution with only 10% water by volume and systematically
      decreasing their x-ray attenuation coefficients by doping with microbubbles that
      are originally designed to be used as lightweight additives for paints and crack
      fillers. For demonstration, we mimic breast glandular and adipose tissues by
      using such gelatin materials and also study the feasibility of 3D printing them
      based on the extrusion-based technique. Results from x-ray spectroscopy (15-45
      keV) show the materials to have stable x-ray attenuation properties of glandular
      and adipose tissues over a period of two months. Micro-CT analysis of
      independently prepared samples shows the materials to be uniform and easy to
      reproduce with minimum variability in attenuation values. These materials can be
      used to 3D print realistic phantoms that mimic x-ray properties of various
      biological tissues.

PMID- 29633956
TI  - Multi-threading performance of Geant4, MCNP6, and PHITS Monte Carlo codes for
      tetrahedral-mesh geometry.
AB  - In this study, the multi-threading performance of the Geant4, MCNP6, and PHITS
      codes was evaluated as a function of the number of threads (N) and the complexity
      of the tetrahedral-mesh phantom. For this, three tetrahedral-mesh phantoms of
      varying complexity (simple, moderately complex, and highly complex) were prepared
      and implemented in the three different Monte Carlo codes, in photon and neutron
      transport simulations. Subsequently, for each case, the initialization time,
      calculation time, and memory usage were measured as a function of the number of
      threads used in the simulation. It was found that for all codes, the
      initialization time significantly increased with the complexity of the phantom,
      but not with the number of threads. Geant4 exhibited much longer initialization
      time than the other codes, especially for the complex phantom (MRCP). The
      improvement of computation speed due to the use of a multi-threaded code was
      calculated as the speed-up factor, the ratio of the computation speed on a multi
      threaded code to the computation speed on a single-threaded code. Geant4 showed
      the best multi-threading performance among the codes considered in this study,
      with the speed-up factor almost linearly increasing with the number of threads,
      reaching ~30 when N  =  40. PHITS and MCNP6 showed a much smaller increase of the
      speed-up factor with the number of threads. For PHITS, the speed-up factors were
      low when N  =  40. For MCNP6, the increase of the speed-up factors was better,
      but they were still less than ~10 when N  =  40. As for memory usage, Geant4 was
      found to use more memory than the other codes. In addition, compared to that of
      the other codes, the memory usage of Geant4 more rapidly increased with the
      number of threads, reaching as high as ~74 GB when N  =  40 for the complex
      phantom (MRCP). It is notable that compared to that of the other codes, the
      memory usage of PHITS was much lower, regardless of both the complexity of the
      phantom and the number of threads, hardly increasing with the number of threads
      for the MRCP.

PMID- 29633957
TI  - Inverse optimization of objective function weights for treatment planning using
      clinical dose-volume histograms.
AB  - We developed and evaluated a novel inverse optimization (IO) model to estimate
      objective function weights from clinical dose-volume histograms (DVHs). These
      weights were used to solve a treatment planning problem to generate 'inverse
      plans' that had similar DVHs to the original clinical DVHs. Our methodology was
      applied to 217 clinical head and neck cancer treatment plans that were previously
      delivered at Princess Margaret Cancer Centre in Canada. Inverse plan DVHs were
      compared to the clinical DVHs using objective function values, dose-volume
      differences, and frequency of clinical planning criteria satisfaction. Median
      differences between the clinical and inverse DVHs were within 1.1 Gy. For most
      structures, the difference in clinical planning criteria satisfaction between the
      clinical and inverse plans was at most 1.4%. For structures where the two plans
      differed by more than 1.4% in planning criteria satisfaction, the difference in
      average criterion violation was less than 0.5 Gy. Overall, the inverse plans were
      very similar to the clinical plans. Compared with a previous inverse optimization
      method from the literature, our new inverse plans typically satisfied the same or
      more clinical criteria, and had consistently lower fluence heterogeneity.
      Overall, this paper demonstrates that DVHs, which are essentially summary
      statistics, provide sufficient information to estimate objective function weights
      that result in high quality treatment plans. However, as with any summary
      statistic that compresses three-dimensional dose information, care must be taken
      to avoid generating plans with undesirable features such as hotspots; our
      computational results suggest that such undesirable spatial features were
      uncommon. Our IO-based approach can be integrated into the current clinical
      planning paradigm to better initialize the planning process and improve planning
      efficiency. It could also be embedded in a knowledge-based planning or adaptive
      radiation therapy framework to automatically generate a new plan given a
      predicted or updated target DVH, respectively.

PMID- 29633958
TI  - MR-ARFI-based method for the quantitative measurement of tissue elasticity:
      application for monitoring HIFU therapy.
AB  - Monitoring thermal therapies through medical imaging is essential in order to
      ensure that they are safe, efficient and reliable. In this paper, we propose a
      new approach, halfway between MR acoustic radiation force imaging (MR-ARFI) and
      MR elastography (MRE), allowing for the quantitative measurement of the elastic
      modulus of tissue in a highly localized manner. It relies on the simulation of
      the MR-ARFI profile, which depends on tissue biomechanical properties, and on the
      identification of tissue elasticity through the fitting of experimental
      displacement images measured using rapid MR-ARFI. This method was specifically
      developed to monitor MR-guided high intensity focused ultrasound (MRgHIFU)
      therapy. Elasticity changes were followed during HIFU ablations (N  =  6)
      performed ex vivo in porcine muscle samples, and were compared to temperature
      changes measured by MR-thermometry. Shear modulus was found to increase
      consistently and steadily a few seconds after the heating started, and such
      changes were found to be irreversible. The shear modulus was found to increase
      from 1.49  +/-  0.48 kPa (before ablation) to 3.69  +/-  0.93 kPa (after ablation
      and cooling). Thanks to its ability to perform quantitative elasticity
      measurements in a highly localized manner around the focal spot, this method
      proved to be particularly attractive for monitoring HIFU ablations.

PMID- 29633959
TI  - Local deformation gradients in epitaxial Pb(Zr0.2Ti0.8)O3 layers investigated by
      transmission electron microscopy.
AB  - Lead zirconate titanate samples are used for their piezoelectric and
      ferroelectric properties in various types of micro-devices. Epitaxial layers of
      tetragonal perovskites have a tendency to relax by forming [Formula: see text]
      ferroelastic domains. The accommodation of the a/c/a/c polydomain structure on a
      flat substrate leads to nanoscale deformation gradients which locally influence
      the polarization by flexoelectric effect. Here, we investigated the deformation
      fields in epitaxial layers of Pb(Zr0.2Ti0.8)O3 grown on SrTiO3 substrates using
      transmission electron microscopy (TEM). We found that the deformation gradients
      depend on the domain walls inclination ([Formula: see text] or [Formula: see
      text] to the substrate interface) of the successive [Formula: see text] domains
      and we describe three different a/c/a domain configurations: one configuration
      with parallel a-domains and two configurations with perpendicular a-domains (V
      shaped and hat-[Formula: see text]-shaped). In the parallel configuration, the c
      domains contain horizontal and vertical gradients of out-of-plane deformation. In
      the V-shaped and hat-[Formula: see text]-shaped configurations, the c-domains
      exhibit a bending deformation field with vertical gradients of in-plane
      deformation. Each of these configurations is expected to have a different
      influence on the polarization and so the local properties of the film. The
      deformation gradients were measured using dark-field electron holography, a TEM
      technique, which offers a good sensitivity (0.1%) and a large field-of-view
      (hundreds of nanometers). The measurements are compared with finite element
      simulations.

PMID- 29633961
TI  - Benchmark study of ionization potentials and electron affinities of armchair
      single-walled carbon nanotubes using density functional theory.
AB  - The intrinsic parameters of carbon nanotubes (CNTs) such as ionization potential
      (IP) and electron affinity (EA) are closely related to their unique properties
      and associated applications. In this work, we demonstrated the success of optimal
      tuning method based on range-separated (RS) density functionals for both accurate
      and efficient prediction of vertical IPs and electron affinities (EAs) of a
      series of armchair single-walled carbon nanotubes C20n H20 (n  =  2-6) compared
      to the high-level IP/EA equation-of-motion coupled-cluster method with single and
      double substitutions (IP/EA-EOM-CCSD). Notably, the resulting frontier orbital
      energies (-epsilon HOMO and -epsilon LUMO) from the tuning method exhibit an
      excellent approximation to the corresponding IPs and EAs, that significantly
      outperform other conventional density functionals. In addition, it is suggested
      that the RS density functionals that possess both a fixed amount of exact
      exchange in the short-range and a correct long-range asymptotic behavior are
      suitable for calculating electronic structures of finite-sized CNTs. Next the
      performance of density functionals for description of various molecular
      properties such as chemical potential, hardness and electrophilicity are assessed
      as a function of tube length. Thanks to the efficiency and accuracy of this
      tuning method, the related behaviors of much longer armchair single-walled CNTs
      until C200H20 were studied. Lastly, the present work is proved to provide an
      efficient theoretical tool for future materials design and reliable
      characterization of other interesting properties of CNT-based systems.

PMID- 29633960
TI  - Superpixel-based and boundary-sensitive convolutional neural network for
      automated liver segmentation.
AB  - Segmentation of liver in abdominal computed tomography (CT) is an important step
      for radiation therapy planning of hepatocellular carcinoma. Practically, a fully
      automatic segmentation of liver remains challenging because of low soft tissue
      contrast between liver and its surrounding organs, and its highly deformable
      shape. The purpose of this work is to develop a novel superpixel-based and
      boundary sensitive convolutional neural network (SBBS-CNN) pipeline for automated
      liver segmentation. The entire CT images were first partitioned into superpixel
      regions, where nearby pixels with similar CT number were aggregated. Secondly, we
      converted the conventional binary segmentation into a multinomial classification
      by labeling the superpixels into three classes: interior liver, liver boundary,
      and non-liver background. By doing this, the boundary region of the liver was
      explicitly identified and highlighted for the subsequent classification. Thirdly,
      we computed an entropy-based saliency map for each CT volume, and leveraged this
      map to guide the sampling of image patches over the superpixels. In this way,
      more patches were extracted from informative regions (e.g. the liver boundary
      with irregular changes) and fewer patches were extracted from homogeneous
      regions. Finally, deep CNN pipeline was built and trained to predict the
      probability map of the liver boundary. We tested the proposed algorithm in a
      cohort of 100 patients. With 10-fold cross validation, the SBBS-CNN achieved mean
      Dice similarity coefficients of 97.31  +/-  0.36% and average symmetric surface
      distance of 1.77  +/-  0.49 mm. Moreover, it showed superior performance in
      comparison with state-of-art methods, including U-Net, pixel-based CNN, active
      contour, level-sets and graph-cut algorithms. SBBS-CNN provides an accurate and
      effective tool for automated liver segmentation. It is also envisioned that the
      proposed framework is directly applicable in other medical image segmentation
      scenarios.

PMID- 29633962
TI  - Computation of reliable textural indices from multimodal brain MRI: suggestions
      based on a study of patients with diffuse intrinsic pontine glioma.
AB  - Few methodological studies regarding widely used textural indices robustness in
      MRI have been reported. In this context, this study aims to propose some rules to
      compute reliable textural indices from multimodal 3D brain MRI. Diagnosis and
      post-biopsy MR scans including T1, post-contrast T1, T2 and FLAIR images from
      thirty children with diffuse intrinsic pontine glioma (DIPG) were considered. The
      hybrid white stripe method was adapted to standardize MR intensities. Sixty
      textural indices were then computed for each modality in different regions of
      interest (ROI), including tumor and white matter (WM). Three types of intensity
      binning were compared [Formula: see text]: constant bin width and relative
      bounds; [Formula: see text] constant number of bins and relative bounds;
      [Formula: see text] constant number of bins and absolute bounds. The impact of
      the volume of the region was also tested within the WM. First, the mean Hellinger
      distance between patient-based intensity distributions decreased by a factor
      greater than 10 in WM and greater than 2.5 in gray matter after standardization.
      Regarding the binning strategy, the ranking of patients was highly correlated for
      188/240 features when comparing [Formula: see text] with [Formula: see text], but
      for only 20 when comparing [Formula: see text] with [Formula: see text], and nine
      when comparing [Formula: see text] with [Formula: see text]. Furthermore, when
      using [Formula: see text] or [Formula: see text] texture indices reflected tumor
      heterogeneity as assessed visually by experts. Last, 41 features presented
      statistically significant differences between contralateral WM regions when ROI
      size slightly varies across patients, and none when using ROI of the same size.
      For regions with similar size, 224 features were significantly different between
      WM and tumor. Valuable information from texture indices can be biased by
      methodological choices. Recommendations are to standardize intensities in MR
      brain volumes, to use intensity binning with constant bin width, and to define
      regions with the same volumes to get reliable textural indices.

PMID- 29633963
TI  - Ab initio study for the IR spectroscopy of PbTiO3 and PbZrO3, primary blocks of
      PbZr1-x Ti x O3.
AB  - PbTiO3 (PT) and PbZrO3 (PZ) are the two primary blocks of the solid solution
      PbZr1-x Ti x O3 (PZT). They can be modelled in different ways; but, in order to
      do comparable DFT calculations on PZT, with different values of x, one must find
      a unique method that can be used for both PT and PZ. In particular, we want to
      evaluate their vibrational properties to compare them with experimental data.
      Density functional theory (DFT) is used to perform structure geometry
      optimizations and electronic structure calculations, both on low- and high
      temperature phase. Then, harmonic vibrational frequencies of their low
      temperature phase are determined for transverse and longitudinal optical (TO &
      LO) phonons. Moreover, a detailed study of the eigenvectors shows that accurate
      calculations are necessary to correctly interpret and understand the IR spectra.
      In the end, the comparison of our theoretical results with previous experimental
      and theoretical data confirm the strong potential of the SOGGA (second-order
      generalized gradient approximation) functional to correctly describe PT, PZ and,
      hopefully, PZT; especially their structural and vibrational properties.

PMID- 29633964
TI  - Simplified DFT methods for consistent structures and energies of large systems.
AB  - Kohn-Sham density functional theory (DFT) is routinely used for the fast
      electronic structure computation of large systems and will most likely continue
      to be the method of choice for the generation of reliable geometries in the
      foreseeable future. Here, we present a hierarchy of simplified DFT methods
      designed for consistent structures and non-covalent interactions of large systems
      with particular focus on molecular crystals. The covered methods are a minimal
      basis set Hartree-Fock (HF-3c), a small basis set screened exchange hybrid
      functional (HSE-3c), and a generalized gradient approximated functional evaluated
      in a medium-sized basis set (B97-3c), all augmented with semi-classical
      correction potentials. We give an overview on the methods design, a comprehensive
      evaluation on established benchmark sets for geometries and lattice energies of
      molecular crystals, and highlight some realistic applications on large organic
      crystals with several hundreds of atoms in the primitive unit cell.

PMID- 29633965
TI  - Crystal structure of chorismate mutase from Burkholderia phymatum.
AB  - The bacterium Burkholderia phymatum is a promiscuous symbiotic nitrogen-fixating
      bacterium that belongs to one of the largest groups of Betaproteobacteria. Other
      Burkholderia species are known to cause disease in plants and animals, and some
      are potential agents for biological warfare. Structural genomics efforts include
      characterizing the structures of enzymes from pathways that can be targeted for
      drug development. As part of these efforts, chorismate mutase from B. phymatum
      was produced and crystallized, and a 1.95 A resolution structure is reported.
      This enzyme shares less than 33% sequence identity with other homologs of known
      structure. There are two classes of chorismate mutase: AroQ and AroH. The
      bacterial subclass AroQgamma has reported roles in virulence. Chorismate mutase
      from B. phymatum has the prototypical AroQgamma topology and retains the
      characteristic chorismate mutase active site. This suggests that substrate-based
      chorismate mutase inhibitors will not be specific and are likely to affect
      beneficial bacteria such as B. phymatum.

PMID- 29633966
TI  - Crystal structure of pyrimidine-nucleoside phosphorylase from Bacillus subtilis
      in complex with imidazole and sulfate.
AB  - Pyrimidine-nucleoside phosphorylase catalyzes the phosphorolytic cleavage of
      thymidine and uridine with equal activity. Investigation of this protein is
      essential for anticancer drug design. Here, the structure of this protein from
      Bacillus subtilis in complex with imidazole and sulfate is reported at 1.9 A
      resolution, which is an improvement on the previously reported structure at 2.6 A
      resolution. The localization and position of imidazole in the nucleoside-binding
      site reflects the possible binding of ligands that possess an imidazole ring.

PMID- 29633967
TI  - Bacteriophage N4 large terminase: expression, purification and X-ray
      crystallographic analysis.
AB  - Genome packaging is a critical step in the assembly of dsDNA bacteriophages and
      is carried out by a powerful molecular motor known as the large terminase. To
      date, wild-type structures of only two large terminase proteins are available,
      and more structural information is needed to understand the genome-packaging
      mechanism. Towards this goal, the large and small terminase proteins from
      bacteriophage N4, which infects the Escherichia coli K12 strain, have been
      cloned, expressed and purified. The purified putative large terminase protein
      hydrolyzes ATP, and this is enhanced in the presence of the small terminase. The
      large terminase protein was crystallized using the sitting-drop vapour-diffusion
      method and the crystal diffracted to 2.8 A resolution using a home X-ray source.
      Analysis of the X-ray diffraction data showed that the crystal belonged to space
      group P212121, with unit-cell parameters a = 53.7, b = 93.6, c = 124.9 A, alpha =
      beta = gamma = 90 degrees . The crystal had a solvent content of 50.2% and
      contained one molecule in the asymmetric unit.

PMID- 29633968
TI  - Structural view of the helicase reveals that Zika virus uses a conserved
      mechanism for unwinding RNA.
AB  - Recent studies suggest a link between infection by Zika virus (ZIKV) and the
      development of neurological complications. The lack of ZIKV-specific therapeutics
      has alarmed healthcare professionals worldwide. Here, crystal structures of apo
      and AMPPNP- and Mn2+-bound forms of the essential helicase of ZIKV refined to
      1.78 and 1.3 A resolution, respectively, are reported. The structures reveal a
      conserved trimodular topology of the helicase. ATP and Mn2+ are tethered between
      two RecA-like domains by conserved hydrogen-bonding interactions. The binding of
      ligands induces the movement of backbone Calpha and side-chain atoms. Numerous
      solvent molecules are observed in the vicinity of the AMPPNP, suggesting a role
      in catalysis. These high-resolution structures could be useful for the design of
      inhibitors targeting the helicase of ZIKV for the treatment of infections caused
      by ZIKV.

PMID- 29633969
TI  - Structure of proliferating cell nuclear antigen (PCNA) bound to an APIM peptide
      reveals the universality of PCNA interaction.
AB  - Proliferating cell nuclear antigen (PCNA) provides a molecular platform for
      numerous protein-protein interactions in DNA metabolism. A large number of
      proteins associated with PCNA have a well characterized sequence termed the PCNA
      interacting protein box motif (PIPM). Another PCNA-interacting sequence termed
      the AlkB homologue 2 PCNA-interacting motif (APIM), comprising the five consensus
      residues (K/R)-(F/Y/W)-(L/I/V/A)-(L/I/V/A)-(K/R), has also been identified in
      various proteins. In contrast to that with PIPM, the PCNA-APIM interaction is
      less well understood. Here, the crystal structure of PCNA bound to a peptide
      carrying an APIM consensus sequence, RFLVK, was determined and structure-based
      interaction analysis was performed. The APIM peptide binds to the PIPM-binding
      pocket on PCNA in a similar way to PIPM. The phenylalanine and leucine residues
      within the APIM consensus sequence and a hydrophobic residue that precedes the
      APIM consensus sequence are crucially involved in interactions with the
      hydrophobic pocket of PCNA. This interaction is essential for overall binding.
      These results provide a structural basis for regulation of the PCNA interaction
      and might aid in the development of specific inhibitors of this interaction.

PMID- 29633970
TI  - Crystal structure of RecR, a member of the RecFOR DNA-repair pathway, from
      Pseudomonas aeruginosa PAO1.
AB  - DNA damage is usually lethal to all organisms. Homologous recombination plays an
      important role in the DNA damage-repair process in prokaryotic organisms. Two
      pathways are responsible for homologous recombination in Pseudomonas aeruginosa:
      the RecBCD pathway and the RecFOR pathway. RecR is an important regulator in the
      RecFOR homologous recombination pathway in P. aeruginosa. It forms complexes with
      RecF and RecO that can facilitate the loading of RecA onto ssDNA in the RecFOR
      pathway. Here, the crystal structure of RecR from P. aeruginosa PAO1 (PaRecR) is
      reported. PaRecR crystallizes in space group P6122, with two monomers per
      asymmetric unit. Analytical ultracentrifugation data show that PaRecR forms a
      stable dimer, but can exist as a tetramer in solution. The crystal structure
      shows that dimeric PaRecR forms a ring-like tetramer architecture via crystal
      symmetry. The presence of a ligand in the Walker B motif of one RecR subunit
      suggests a putative nucleotide-binding site.

PMID- 29633971
TI  - The putative compatible solute-binding protein ProX from Mycobacterium
      tuberculosis H37Rv: biochemical characterization and crystallographic data.
AB  - In Mycobacterium tuberculosis, the proX gene encodes a putative compatible solute
      binding protein (MtProX). However, it was found through sequence alignment that
      the MtProX protein has very different ligand-binding residues compared with other
      compatible solute-binding proteins, implying that MtProX may bind to ligands that
      are as yet uncharacterized. In this work, it was demonstrated that MtProX binds
      to polyphenols such as phloretin, monoacetylphloroglucinol and 2,4
      dihydroxyacetophloroglucinol with dissociation constants between 20 and 70 uM.
      Crystals of MtProX were obtained using a precipitant consisting of 0.2 M NaCl,
      0.1 M Tris pH 8.5, 25%(w/v) polyethylene glycol 3350. The crystals diffracted to
      2.10 A resolution and belonged to space group P43212, with unit-cell parameters a
      = b = 90.17, c = 161.92 A, alpha = beta = gamma = 90.0 degrees . Assuming the
      presence of two MtProX molecules in the asymmetric unit, the Matthews coefficient
      was calculated to be 2.74 A3 Da-1, which corresponds to a solvent content of 55%.

PMID- 29633972
TI  - High-resolution crystal structure of Streptococcus agalactiae glyceraldehyde-3
      phosphate dehydrogenase.
AB  - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a multifunctional enzyme that
      plays critical roles in bacterial pathogenesis in some pathogenic bacteria. In
      this study, the crystal structure of group B streptococcus GAPDH was determined
      at 1.36 A resolution. The structure contained an asymmetric mixed holo tetramer,
      with two NAD ligands bound to two protomers. Further structural analysis
      identified interesting phosphate ion-binding sites, which shed light on its
      catalytic mechanism.

PMID- 29633974
TI  - Structural view of the 2A protease from human rhinovirus C15.
AB  - The majority of outbreaks of the common cold are caused by rhinoviruses. The 2A
      protease (2Apro) of human rhinoviruses (HRVs) is known to play important roles in
      the propagation of the virus and the modulation of host signal pathways to
      facilitate viral replication. The 2Apro from human rhinovirus C15 (HRV-C15) has
      been expressed in Escherichia coli and purified by affinity chromatography, ion
      exchange chromatography and gel-filtration chromatography. The crystals
      diffracted to 2.6 A resolution. The structure was solved by molecular replacement
      using the structure of 2Apro from coxsackievirus A16 (CVA16) as the search model.
      The structure contains a conserved His-Asp-Cys catalytic triad and a Zn2+-binding
      site. Comparison with other 2Apro structures from enteroviruses reveals that the
      substrate-binding cleft of 2Apro from HRV-C15 exhibits a more open conformation,
      which presumably favours substrate binding.

PMID- 29633973
TI  - The crystal structure of the drug target Mycobacterium tuberculosis methionyl
      tRNA synthetase in complex with a catalytic intermediate.
AB  - Mycobacterium tuberculosis is a pathogenic bacterial infectious agent that is
      responsible for approximately 1.5 million human deaths annually. Current
      treatment requires the long-term administration of multiple medicines with
      substantial side effects. Lack of compliance, together with other factors, has
      resulted in a worrisome increase in resistance. New treatment options are
      therefore urgently needed. Here, the crystal structure of methionyl-tRNA
      synthetase (MetRS), an enzyme critical for protein biosynthesis and therefore a
      drug target, in complex with its catalytic intermediate methionyl adenylate is
      reported. Phenylalanine 292 of the M. tuberculosis enzyme is in an 'out'
      conformation and barely contacts the adenine ring, in contrast to other MetRS
      structures where ring stacking occurs between the adenine and a protein side
      chain ring in the 'in' conformation. A comparison with human cytosolic MetRS
      reveals substantial differences in the active site as well as regarding the
      position of the connective peptide subdomain 1 (CP1) near the active site, which
      bodes well for arriving at selective inhibitors. Comparison with the human
      mitochondrial enzyme at the amino-acid sequence level suggests that arriving at
      inhibitors with higher affinity for the mycobacterial enzyme than for the
      mitochondrial enzyme might be achievable.

PMID- 29633975
TI  - Crystallization of the rice immune receptor RGA5A_S with the rice blast fungus
      effector AVR1-CO39 prepared via mixture and tandem strategies.
AB  - RGA5 is a component of the Pia resistance-protein pair (RGA4/RGA5) from Oryza
      sativa L. japonica. It acts as an immune receptor that directly recognizes the
      effector AVR1-CO39 from Magnaporthe oryzae via a C-terminal non-LRR domain
      (RGA5A_S). The interaction between RGA5A_S and AVR1-CO39 relieves the repression
      of RGA4, leading to effector-independent cell death. To determine the structure
      of the complex of RGA5A_S and AVR1-CO39 and to understand the details of this
      interaction, the complex was prepared by fusing the proteins together, by mixing
      them in vitro or by co-expressing them in one host cell. Samples purified via the
      first two strategies were crystallized under two different conditions. A mixture
      of AVR1-CO39 and RGA5A_S (complex I) crystallized in 1.1 M ammonium tartrate
      dibasic, 0.1 M sodium acetate-HCl pH 4.6, while crystals of the fusion complex
      RGA5A_S-TEV-AVR1-CO39 (complex II) were grown in 2 M NaCl. The crystal of complex
      I belonged to space group P3121, with unit-cell parameters a = b = 66.2, c =
      108.8 A, alpha = beta = 90, gamma = 120 degrees . The crystals diffracted to a
      Bragg spacing of 2.4 A, and one molecule each of RGA5A_S and AVR1-CO39 were
      present in the asymmetric unit of the initial model. The crystal of complex II
      belonged to space group I4, with unit-cell parameters a = b = 137.4, c = 66.2 A,
      alpha = beta = gamma = 90 degrees . The crystals diffracted to a Bragg spacing of
      2.72 A, and there were two molecules of RGA5A_S and two molecules of AVR1-CO39 in
      the asymmetric unit of the initial model. Further structural characterization of
      the interaction between RGA5A_S and AVR1-CO39 will lead to a better understanding
      of the mechanism underlying effector recognition by R proteins.

PMID- 29633976
TI  - Transplantation in Germany: Erratum.

PMID- 29633977
TI  - Use of Everolimus in Liver Transplantation: Recommendations From a Working Group:
      Erratum.

PMID- 29633978
TI  - Paying It Forward: Live Kidney Donation Now to (POSSIBLY) Benefit a Long-term
      Future Recipient.

PMID- 29633979
TI  - The Emerging Importance of Skeletal Muscle Function in Assessing Candidates for
      Transplantation.

PMID- 29633980
TI  - Severe Allograft Rejection and Autoimmune Hemolytic Anemia After Anti-PD1 Therapy
      in a Kidney Transplanted Patient.

PMID- 29633981
TI  - Kidney Paired Donation and the "Valuable Consideration" Problem: The Experiences
      of Australia, Canada, and the United States.
AB  - As organ donation rates remain unable to meet the needs of individuals waiting
      for transplants, it is necessary to identify reasons for this shortage and
      develop solutions to address it. The introduction of kidney paired donation (KPD)
      programs represents one such innovation that has become a valuable tool in
      donation systems around the world. Although KPD has been successful in increasing
      kidney donation and transplantation, there are lingering questions about its
      legality. Donation through KPD is done in exchange for-and with the expectation
      of-a reciprocal kidney donation and transplantation. It is this reciprocity that
      has caused concern about whether KPD complies with existing law. Organ donation
      systems around the world are almost universally structured to legally prohibit
      the commercial exchange of organs. Australia, Canada, and the United States have
      accomplished this goal by prohibiting the exchange of an organ for "valuable
      consideration," which is a legal term that has not historically been limited to
      monetary exchange. Whether or not KPD programs violate this legislative
      prohibition will depend on the specific legislative provision being considered,
      and the legal system and case law of the particular jurisdiction in question.
      This article compares the experiences of Australia, Canada, and the United States
      in determining the legality of KPD and highlights the need for legal clarity and
      flexibility as donation and transplantation systems continue to evolve.

PMID- 29633983
TI  - Effects of replacing diet beverages with water on weight loss and weight
      maintenance: 18-month follow-up, randomized clinical trial.
AB  - BACKGROUND: Beneficial effects of replacing diet beverages (DBs) with water on
      weight loss, during a 24-week hypoenergetic diet were previously observed.
      However, it is not known whether this difference is sustained during a subsequent
      12-month weight maintenance period. OBJECTIVE: To evaluate effects of replacing
      DBs with water on body weight maintenance over a 12-month period in participants
      who undertook a 6-month weight loss plan. DESIGN: Seventy-one obese and
      overweight adult women (body mass index (BMI): 27-40 kg m-2; age: 18-50 years)
      who usually consumed DBs in their diet were randomly assigned to either
      substitute water for DBs (water group: 35) or continue drinking DBs five times
      per week (DBs group: 36) after their lunch for the 6-month weight loss
      intervention and subsequent 12-month weight maintenance program. RESULTS: A total
      of 71 participants who were randomly assigned were included in the study by using
      an intention-to-treat analysis. Greater additional weight loss (mean+/-s.d.) in
      the water group was observed compared with the DBs group after the 12-month
      follow-up period (-1.7+/-2.8 vs -0.1+/-2.7 kg, P=0.001). BMI decreased more in
      the water group than in the DBs group (-0.7+/-1 vs -0.05+/-1.1 kg m-2, P=0.003).
      There was also a greater reduction in fasting insulin levels (-0.5+/-1.4 vs 
      0.02+/-1.5 mmol l-1, P=0.023), better improvement in homeostasis model assessment
      of insulin resistance (-0.2+/-0.4 vs -0.1+/-0.3, P=0.013) and a greater decrease
      in 2-h postprandial plasma glucose (-0.2+/-0.3 vs -0.1+/-0.3 mmol l-1, P<0.001)
      in the water group compared with the DBs over the 12-month weight maintenance
      period. CONCLUSIONS: Replacement of DBs with water after the main meal in women
      who were regular users of DBs may cause further weight reduction during a 12
      month weight maintenance program. It may also offer benefits in carbohydrate
      metabolism including improvement of insulin resistance over the long-term weight
      maintenance period.

PMID- 29633984
TI  - Tundra landform and vegetation productivity trend maps for the Arctic Coastal
      Plain of northern Alaska.
AB  - Arctic tundra landscapes are composed of a complex mosaic of patterned ground
      features, varying in soil moisture, vegetation composition, and surface hydrology
      over small spatial scales (10-100 m). The importance of microtopography and
      associated geomorphic landforms in influencing ecosystem structure and function
      is well founded, however, spatial data products describing local to regional
      scale distribution of patterned ground or polygonal tundra geomorphology are
      largely unavailable. Thus, our understanding of local impacts on regional scale
      processes (e.g., carbon dynamics) may be limited. We produced two key
      spatiotemporal datasets spanning the Arctic Coastal Plain of northern Alaska
      (~60,000 km2) to evaluate climate-geomorphological controls on arctic tundra
      productivity change, using (1) a novel 30 m classification of polygonal tundra
      geomorphology and (2) decadal-trends in surface greenness using the Landsat
      archive (1999-2014). These datasets can be easily integrated and adapted in an
      array of local to regional applications such as (1) upscaling plot-level
      measurements (e.g., carbon/energy fluxes), (2) mapping of soils, vegetation, or
      permafrost, and/or (3) initializing ecosystem biogeochemistry, hydrology, and/or
      habitat modeling.

PMID- 29633982
TI  - Necroptosis Is Involved in CD4+ T Cell-Mediated Microvascular Endothelial Cell
      Death and Chronic Cardiac Allograft Rejection.
AB  - BACKGROUND: Despite advances in immunosuppressive therapies, the rate of chronic
      transplant loss remains substantial. Organ injury involves various forms of cell
      death including apoptosis and necrosis. We now recognize that early injury of
      cardiac transplants involves a newly described form of programmed necrotic cell
      death, termed necroptosis. Because this involves receptor-interacting protein
      (RIP) kinase 1/3, this study aimed to establish the role of RIP3 in chronic
      cardiac allograft rejection. METHODS: We used major histocompatibility complex
      class II mismatched C57BL/6N (H-2; B6) or B6.RIP3 (H-2; RIP3) mice to B6.C-H-2
      (H2-Ab1; bm12) mouse cardiac transplantation. Microvascular endothelial cells
      (MVEC) were developed from B6 and RIP3 cardiac grafts. RESULT: CD4 T cell
      mediated cardiac graft rejection is inhibited using RIP3 deficient donor grafts,
      with reduced cellular infiltration and vasculopathy compared with wild type
      cardiac grafts. Alloreactive CD4 T cell-mediated MVEC death involves TNFalpha,
      Fas ligand (FasL) and granzyme B. Although necroptosis and release of danger
      molecule high-mobility group box 1 are eliminated by the absence of RIP3, CD4 T
      cells had attenuated MVEC death through granzyme B and FasL. CONCLUSIONS: CD4 T
      cell-mediated MVEC death involves in TNFalpha, FasL and granzyme B. Necroptotic
      cell death and release of the danger molecule may promote inflammatory responses
      and transplant rejection. Although loss of RIP3 does not eliminate alloimmune
      responses, chronic graft injury is reduced. RIP3 is an important therapeutic
      target but additional granzyme and caspases inhibition is required for
      sufficiently improving long-term graft survival.

PMID- 29633985
TI  - Ensemble of European regional climate simulations for the winter of 2013 and 2014
      from HadAM3P-RM3P.
AB  - Large data sets used to study the impact of anthropogenic climate change on the
      2013/14 floods in the UK are provided. The data consist of perturbed initial
      conditions simulations using the Weather@Home regional climate modelling
      framework. Two different base conditions, Actual, including atmospheric
      conditions (anthropogenic greenhouse gases and human induced aerosols) as at
      present and Natural, with these forcings all removed are available. The data set
      is made up of 13 different ensembles (2 actual and 11 natural) with each having
      more than 7500 members. The data is available as NetCDF V3 files representing
      monthly data within the period of interest (1st Dec 2013 to 15th February 2014)
      for both a specified European region at a 50 km horizontal resolution and
      globally at N96 resolution. The data is stored within the UK Natural and
      Environmental Research Council Centre for Environmental Data Analysis repository.

PMID- 29633986
TI  - Massively parallel recordings in macaque motor cortex during an instructed
      delayed reach-to-grasp task.
AB  - We publish two electrophysiological datasets recorded in motor cortex of two
      macaque monkeys during an instructed delayed reach-to-grasp task, using
      chronically implanted 10-by-10 Utah electrode arrays. We provide a) raw neural
      signals (sampled at 30 kHz), b) time stamps and spike waveforms of offline sorted
      single and multi units (93/49 and 156/19 SUA/MUA for the two monkeys,
      respectively), c) trial events and the monkey's behavior, and d) extensive
      metadata hierarchically structured via the odML metadata framework (including
      quality assessment post-processing steps, such as trial rejections). The dataset
      of one monkey contains a simultaneously saved record of the local field potential
      (LFP) sampled at 1 kHz. To load the datasets in Python, we provide code based on
      the Neo data framework that produces a data structure which is annotated with
      relevant metadata. We complement this loading routine with an example code
      demonstrating how to access the data objects (e.g., raw signals) contained in
      such structures. For Matlab users, we provide the annotated data structures as
      mat files.

PMID- 29633987
TI  - The Alexandria library, a quantum-chemical database of molecular properties for
      force field development.
AB  - Data quality as well as library size are crucial issues for force field
      development. In order to predict molecular properties in a large chemical space,
      the foundation to build force fields on needs to encompass a large variety of
      chemical compounds. The tabulated molecular physicochemical properties also need
      to be accurate. Due to the limited transparency in data used for development of
      existing force fields it is hard to establish data quality and reusability is
      low. This paper presents the Alexandria library as an open and freely accessible
      database of optimized molecular geometries, frequencies, electrostatic moments up
      to the hexadecupole, electrostatic potential, polarizabilities, and
      thermochemistry, obtained from quantum chemistry calculations for 2704 compounds.
      Values are tabulated and where available compared to experimental data. This
      library can assist systematic development and training of empirical force fields
      for a broad range of molecules.

PMID- 29633988
TI  - A data discovery index for the social sciences.
AB  - This paper describes a novel search index for social and economic research data,
      one that enables users to search up-to-date references for data holdings in these
      disciplines. The index can be used for comparative analysis of publication of
      datasets in different areas of social science. The core of the index is the da|ra
      registration agency's database for social and economic data, which contains high
      quality searchable metadata from registered data publishers. Research data's
      metadata records are harvested from data providers around the world and included
      in the index. In this paper, we describe the currently available indices on
      social science datasets and their shortcomings. Next, we describe the motivation
      behind and the purpose for the data discovery index as a dedicated and curated
      platform for finding social science research data and gesisDataSearch, its user
      interface. Further, we explain the harvesting, filtering and indexing procedure
      and give usage instructions for the dataset index. Lastly, we show that the index
      is currently the most comprehensive and most accessible collection of social
      science data descriptions available.

PMID- 29633990
TI  - Holocene dwarf mammoths from Wrangel Island in the Siberian Arctic.
AB  - THE cause of extinction of the woolly mammoth, Mammuthus primigenius
      (Blumenbach), is still debated. A major environmental change at the Pleistocene
      Holocene boundary, hunting by early man, or both together are among the main
      explanations that have been suggested. But hardly anyone has doubted that
      mammoths had become extinct everywhere by around 9,500 years before present (BP).
      We report here new discoveries on Wrangel Island in the Arctic Ocean that force
      this view to be revised. Along with normal-sized mammoth fossils dating to the
      end of the Pleistocene, numerous teeth of dwarf mammoth dated 7,000-4,000 yr BP
      have been found there. The island is thought to have become separated from the
      mainland by 12,000 yr BP. Survival of a mammoth population may be explained by
      local topography and climatic features, which permitted relictual preservation of
      communities of steppe plants. We interpret the dwarfing of the Wrangel mammoths
      as a result of the insularity effect, combined with a response to the general
      trend towards unfavourable environment in the Holocene.

PMID- 29633989
TI  - Long-term dataset on aquatic responses to concurrent climate change and recovery
      from acidification.
AB  - Concurrent regional and global environmental changes are affecting freshwater
      ecosystems. Decadal-scale data on lake ecosystems that can describe processes
      affected by these changes are important as multiple stressors often interact to
      alter the trajectory of key ecological phenomena in complex ways. Due to the
      practical challenges associated with long-term data collections, the majority of
      existing long-term data sets focus on only a small number of lakes or few
      response variables. Here we present physical, chemical, and biological data from
      28 lakes in the Adirondack Mountains of northern New York State. These data span
      the period from 1994-2012 and harmonize multiple open and as-yet unpublished data
      sources. The dataset creation is reproducible and transparent; R code and all
      original files used to create the dataset are provided in an appendix. This
      dataset will be useful for examining ecological change in lakes undergoing
      multiple stressors.

PMID- 29633992
TI  - Reaction cycles.

PMID- 29633991
TI  - Back-door regulation.

PMID- 29633993
TI  - Lighting up logic.

PMID- 29633994
TI  - Transition between crack patterns in quenched glass plates.
AB  - THE study of fracture is an old topic1, but only recently has an understanding
      begun to emerge of crack formation, propagation and morphology (which is often
      fractal) 2-8. When a brittle material such as glass is broken under tensile
      stress9, the cracks have a complicated morphology10. Fineberg et al.11 showed
      that this process may be caused by a dynamic instability, whereby the speed of
      crack propagation increases until it approaches the speed of sound: at this
      point, complex structures appear. But crack morphology in quasistatic fracture,
      where the speed of the crack tip is much smaller than the speed of sound, can
      also exhibit marked changes12. Here we present studies of crack propagation in
      glass plates caused by sudden but carefully controlled cooling. We observe a
      transition from straight to regular, wavy cracks as the tip speed increases. The
      scaling behaviour of an appropriately defined relaxation time suggests that this
      transition is a Hopf bifurcation13, like those seen in a variety of other
      nonlinear systems. At still higher speeds, the oscillatory cracks split into
      first two and then four or more branches.

PMID- 29633995
TI  - Going with the flow.

PMID- 29633996
TI  - Curtain falls on Britain's nuclear structure facility.

PMID- 29633997
TI  - Support for a unified model of radio galaxies and quasars from isotropic [O II]
      emission.
AB  - UNIFIED models1-3 of radio-loud quasars and powerful radio galaxies suggest that
      they are intrinsically similar objects observed from different angles. This can
      be tested by comparing the isotropically emitted radiation from the spatially
      extended nebulae surrounding the nuclei; the unified models predict that the
      intensities of these emissions should be comparable for the two classes of
      object. But when this prediction was examined4 for the [O III] 5,007-A emission
      line, it was found that quasar [O III] luminosities significantly exceed those of
      otherwise similar radio galaxies. We have measured the spatially integrated [O
      II] 3,727-A emission-line luminosities for a number of quasars and radio galaxies
      taken from the 3C catalogue. Supplementing our data with values from the
      literature, we find no systematic difference in the [O II] luminosities. We argue
      that this emission is indeed isotropic, and that our results are consistent with
      the unification hypothesis; the [O III] line, on the other hand, may still have a
      significant component from the nuclear region, and thus be subject to pronounced
      anisotropic obscuration.

PMID- 29633998
TI  - The laughing physicist.

PMID- 29633999
TI  - Life after death for nuclear physics.

PMID- 29634000
TI  - Mammoths in miniature.

PMID- 29634001
TI  - Hidden message.

PMID- 29634002
TI  - Cambrian sea water preserved as inclusions in marine low-magnesium calcite
      cement.
AB  - THE existence of temporal changes in the chemical composition of the oceans,
      which could provide constraints on the potential variability of the ocean
      atmosphere; system, remains an open question. Assessments of the chemistry of
      ancient oceans have relied largely on analysis of marine precipitates, generally
      carbonate and evaporite minerals1. These studies suggest that, whereas marine
      salinity has remained relatively stable over Phanerozoic time1, magnesium,
      calcium and sulphate concentrations of ancient oceans and CO2 partial pressure of
      ancient atmospheres may have changed2-4. The ratios of isotopes of carbon,
      oxygen, sulphur and strontium also appear to have varied3,5,6. Here we present
      analyses of primary, one-phase fluid inclusions in Cambrian and Ordovician marine
      cements, which appear to represent aliquots of early Palaeozoic oceans. The
      cements have trace element, stable isotope and strontium isotope contents that
      are consistent with their having been precipitated in a Cambrian-Ordovician
      marine environment, and the fluids have marine salinities. As these (apparently
      primary) cements are low-magnesium calcite, unlike the predominantly high
      magnesium calcite and aragonite of today's carbonate precipitates, the chemistry
      of the Cambrian ocean-atmosphere system seems to have been different from that of
      today.

PMID- 29634003
TI  - China in Brief.

PMID- 29634005
TI  - Cool work.

PMID- 29634004
TI  - In peace and in war.

PMID- 29634007
TI  - In at the deep end.

PMID- 29634006
TI  - A young source of optical emission from distant radio galaxies.
AB  - DISTANT radio galaxies provide valuable insights into the properties of the young
      Universe-they are the only known extended optical sources at high redshift and
      might represent an early stage in the formation and evolution of galaxies in
      general. This extended optical emission often has very complex morphologies, but
      the origin of the light is still unclear. Here we report spectroscopic
      observations for several distant radio galaxies (0.75<= z <= 1.1) in which the
      rest-frame spectra exhibit featureless continua between 2,500 A and 5,000 A. We
      see no evidence for the break in the spectrum at 4,000 A expected for an old
      stellar population1-3, and suggest that young stars or scattered emissions from
      the active nuclei are responsible for most of the observed light. In either case,
      this implies that the source of the optical emission is com-parable in age to the
      associated radio source, namely 107 years or less.

PMID- 29634008
TI  - Cracks take a new turn.

PMID- 29634011
TI  - Hacking in court.

PMID- 29634010
TI  - The jewel in the crown.

PMID- 29634012
TI  - No easy answers for UK science.

PMID- 29634013
TI  - Waldegrave says White Paper will not seek radical changes.

PMID- 29634014
TI  - Eye on the marketplace.

PMID- 29634015
TI  - Two circadian oscillators in one cell.
AB  - A CIRCADIAN clock, which continues to oscillate in constant conditions, is almost
      ubiquitous in eukaryotes as well as some prokaryotes1. This class of biological
      oscillators drives daily rhythms as diverse as photosynthesis in plants2 and the
      sleep-wake cycle in man3 and enables organisms to anticipate environmental
      changes or segregate in time-incompatible processes4. Circadian oscillators share
      many properties, suggesting that the clock is a single mechanism, preserved
      throughout evolution, which is capable of controlling all the different circadian
      functions. Here we show that two rhythms in a unicellular organism can, under
      certain experimental conditions, run independently, and thus each rhythm must be
      controlled by its own distinct oscillator.

PMID- 29634016
TI  - It takes two to nano.

PMID- 29634018
TI  - Mind and meaning.

PMID- 29634019
TI  - French voters shun 'greens'.

PMID- 29634021
TI  - Ancient sea water.

PMID- 29634020
TI  - Isotopic evidence for the source of lead in Greenland snows since the late 1960s.
AB  - IN 1969, Murozumi et al.1 demonstrated that the concentration of lead in
      Greenland snow had increased by a factor of 200 since ancient times, and
      concluded that most of this increase was a result of the use of alkyl-leaded
      petrol. Partly because of these findings, the United States and other western
      countries limited the use of lead additives in petrol from about 1970. Recently,
      Boutron et al.2 showed that the lead concentration in Greenland snow had
      decreased by a factor of ~7.5 over the past 20 years, and suggested that this was
      a result of the decline in use of leaded petrol. We present here measurements of
      the 206Pb/207Pb ratio of the lead contained in the samples studied by Boutron et
      al. Because aerosols from the atmosphere above the United States are more
      radiogenic than those from Eurasia, we can trace the relative contributions of
      these two sources in the Greenland lead over the period analysed by Boutron et
      al.We find that the United States was a significant source of lead in the 1970s,
      but it has since declined considerably in relative importance. This decline
      mirrors the decrease in use of leaded petrol in the United States, confirming the
      earlier hypothesis.

PMID- 29634022
TI  - How to make the NPT more effective.

PMID- 29634024
TI  - Web of intrigue.

PMID- 29634023
TI  - Giant African lakes revisited.

PMID- 29634025
TI  - Syria prodded to end human rights abuses.

PMID- 29634027
TI  - Perfect stress.

PMID- 29634028
TI  - Clinton accepts court's ruling on Antarctica.

PMID- 29634030
TI  - Food for thought.

PMID- 29634029
TI  - Guide to authors.

PMID- 29634031
TI  - Intolerant mice.

PMID- 29634033
TI  - Australopithecus afarensis couple.

PMID- 29634032
TI  - Germany avoids large projects in favour of economic payoffs.

PMID- 29634034
TI  - Renovation of Paris museum leaves collection in disarray.

PMID- 29634035
TI  - A purple protist.

PMID- 29634036
TI  - Hard physics.

PMID- 29634038
TI  - MITI reshuffles institutes to keep up with the times.

PMID- 29634037
TI  - Role of sulphur photochemistry in tropical ozone changes after the eruption of
      Mount Pinatubo.
AB  - RECENT observations suggest that the eruption of Mount Pinatubo in June 1991 has
      had a considerable effect on ozone concentrations in the tropical stratosphere
      (refs 1, 2, and J. W. Waters, personal communication). Although stratospheric
      ozone losses following volcanic eruptions are generally attributed to the
      presence of sulphate aerosol3-7, we present model calculations which demonstrate
      that gas-phase sulphur chemistry may have played a part in the tropical ozone
      perturbations that followed the Pinatubo eruption. We find that in the first
      month or so after the eruption, the large amount of SO2 injected into the
      tropical atmosphere catalyses mid-stratospheric ozone production. On the other
      hand, the SO2 cloud absorbs solar radiation, thereby reducing the rate of O2
      photolysis (and hence of ozone production) below it. These two effects cancel
      each other out at an altitude of about 25 kilometres. After one or two months,
      most of the SO2 has been oxidized to sulphate; the efficiency of these two
      mechanisms then becomes negligible (although ozone remains perturbed in the lower
      stratosphere because of its long photochemical lifetime in this region). The
      model features show good agreement with initial ozone measurements following the
      eruption, including both the mid-altitude switch from ozone loss to ozone gain1,
      and the increase and subsequent decrease in the total ozone column2,7.

PMID- 29634039
TI  - Correction: How much does a heart valve implantation cost and what are the health
      care costs afterwards?
AB  - [This corrects the article DOI: 10.1136/openhrt-2017-000672.][This corrects the
      article DOI: 10.1136/openhrt-2017-000672.].

PMID- 29634040
TI  - Correction: Endoscopic perforation during EMR or ESD: who should take care of the
      patient?
AB  - [This corrects the article DOI: 10.1055/s-0044-101348.].

PMID- 29634041
TI  - Corrigendum: Stochastic Individual-Based Modeling of Bacterial Growth and
      Division Using Flow Cytometry.
AB  - [This corrects the article on p. 2626 in vol. 8, PMID: 29354110.].

PMID- 29634042
TI  - Corrigendum: Inducing the Alternative Oxidase Forms Part of the Molecular
      Strategy of Anoxic Survival in Freshwater Bivalves.
AB  - [This corrects the article on p. 100 in vol. 9, PMID: 29527172.].

PMID- 29634044
TI  - Commentary: Advances in Diagnosis and Management of Hemodynamic Instability in
      Neonatal Shock.

PMID- 29634043
TI  - The European Vasculitis Society 2016 Meeting Report.
AB  - The 2016 European Vasculitis Society (EUVAS) meeting, held in Leiden, the
      Netherlands, was centered around phenotypic subtyping in antineutrophil
      cytoplasmic antibody (ANCA)-associated vasculitis (AAV). There were parallel
      meetings of the EUVAS petals, which here report on disease assessment; database;
      and long-term follow-up, registries, genetics, histology, biomarker studies, and
      clinical trials. Studies currently conducted will improve our ability to
      discriminate between different forms of vasculitis. In a project that involves
      the 10-year follow-up of AAV patients, we are working on retrieving data on
      patient and renal survival, relapse rate, the cumulative incidence of
      malignancies, and comorbidities. Across Europe, several vasculitis registries
      were developed covering over 10,000 registered patients. In the near future,
      these registries will facilitate clinical research in AAV on a scale hitherto
      unknown. Current studies on the genetic background of AAV will explore the
      potential prognostic significance of genetic markers and further refine genetic
      associations with distinct disease subsets. The histopathological classification
      of ANCA-associated glomerulonephritis is currently evaluated in light of data
      coming out of a large international validation study. In our continuous search
      for biomarkers to predict clinical outcome, promising new markers are important
      subjects of current research. Over the last 2 decades, a host of clinical trials
      have provided evidence for refinement of therapeutic regimens. We give an
      overview of clinical trials currently under development, and consider refractory
      vasculitis in detail. The goal of EUVAS is to stimulate ongoing research in
      clinical, serological, and histological management and techniques for patients
      with systemic vasculitis, with an outlook on the applicability for clinical
      trials.

PMID- 29634046
TI  - Correction.
AB  - [This corrects the article on p. 74 in vol. 106, PMID: 29339936.].

PMID- 29634045
TI  - Correction: Post-pancreaticoduodenectomy hemorrhage: DSA diagnosis and
      endovascular treatment.
AB  - [This corrects the article DOI: 10.18632/oncotarget.17450.].

PMID- 29634047
TI  - Correction: Subclinical magnesium deficiency: a principal driver of
      cardiovascular disease and a public health crisis.
AB  - [This corrects the article DOI: 10.1136/openhrt-2017-000668.][This corrects the
      article DOI: 10.1136/openhrt-2017-000668.].

PMID- 29634049
TI  - Corrigendum.
AB  - [This corrects the article DOI: 10.1080/2162402X.2017.1408750.].

PMID- 29634048
TI  - Remote Patient Management for Home Dialysis Patients.
AB  - Remote patient management (RPM) offers renal health care providers and patients
      with end-stage kidney disease opportunities to embrace home dialysis therapies
      with greater confidence and the potential to obtain better clinical outcomes.
      Barriers and evidence required to increase adoption of RPM by the nephrology
      community need to be clearly defined. Ten health care providers from specialties
      including nephrology, cardiology, pediatrics, epidemiology, nursing, and health
      informatics with experience in home dialysis and the use of RPM systems gathered
      in Vienna, Austria to discuss opportunities for, barriers to, and system
      requirements of RPM as it applies to the home dialysis patient. Although improved
      outcomes and cost-effectiveness of RPM have been demonstrated in patients with
      diabetes mellitus and heart disease, only observational data on RPM have been
      gathered in patients on dialysis. The current review focused on RPM systems
      currently in use, on how RPM should be integrated into future care, and on the
      evidence needed for optimized implementation to improve clinical and economic
      outcomes. Randomized controlled trials and/or large observational studies could
      inform the most effective and economical use of RPM in home dialysis. These
      studies are needed to establish the value of existing and/or future RPM models
      among patients, policy makers, and health care providers.

PMID- 29634050
TI  - Retraction Note to: Engineering Bacillus licheniformis as a thermophilic platform
      for the production of l-lactic acid from lignocellulose-derived sugars.
AB  - [This retracts the article DOI: 10.1186/s13068-017-0920-z.].

PMID- 29634051
TI  - Identification and characterization of different tissues in blood vessel by
      multiplexed fluorescence lifetimes.
AB  - Herein, fluorescence lifetime imaging microscopy (FLIM) was used to directly
      measure eosin fluorescence lifetimes from H&E-stained umbilical artery, and a
      further utilization of eosin for high-content and multi-target analysis was
      proposed for the first time. Smooth muscles, collagens, and elastic fibers can be
      distinguished by eosin fluorescence lifetimes (P < 0.001). Erythrocytes, smooth
      muscles, elastic fibers, and type I and III collagen from the H&E-stained
      umbilical artery can be simultaneously identified by multiplexed fluorescence
      lifetimes of eosin. Use of eosin and lifetime-based separation is a potential
      method to simplify the special staining for clinicopathologic examination.
      Multiplexed eosin fluorescence lifetimes may be a newly developed method that can
      directly determine the relative content of elastic fiber and collagens from the
      H&E-stained sections. FLIM may have potential applications as an assisted tool in
      the assessment of the severity and complexity of cardiovascular diseases.

PMID- 29634052
TI  - Fabrication of paper-based analytical devices optimized by central composite
      design.
AB  - In this work, an application of a design of experiments approach for the
      optimization of an isoniazid assay on a single-area inkjet-printed paper-based
      analytical device (PAD) is described. For this purpose, a central composite
      design was used for evaluation of the effect of device geometry and amount of
      assay reagents on the efficiency of the proposed device. The factors of interest
      were printed length, width, and sampling volume as factors related to device
      geometry, and amounts of the assay reagents polyvinyl alcohol (PVA), NH4OH, and
      AgNO3. Deposition of the assay reagents was performed by a thermal inkjet
      printer. The colorimetric assay mechanism of this device is based on the chemical
      interaction of isoniazid, ammonium hydroxide, and PVA with silver ions to induce
      the formation of yellow silver nanoparticles (AgNPs). The in situ-formed AgNPs
      can be easily detected by the naked eye or with a simple flat-bed scanner. Under
      optimal conditions, the calibration curve was linear in the isoniazid
      concentration range 0.03-10 mmol L-1 with a relative standard deviation of 3.4%
      (n = 5 for determination of 1.0 mmol L-1). Finally, the application of the
      proposed device for isoniazid determination in pharmaceutical preparations
      produced satisfactory results.

PMID- 29634053
TI  - Correction: Selenium effects on the metabolism of a Se-metabolizing Lactobacillus
      reuteri: analysis of envelope-enriched and extracellular proteomes.
AB  - Correction for 'Selenium effects on the metabolism of a Se-metabolizing
      Lactobacillus reuteri: analysis of envelope-enriched and extracellular proteomes'
      by E. Mangiapane et al., Mol. BioSyst., 2014, 10, 1272-1280.

PMID- 29634054
TI  - Networks of micronized fat crystals grown under static conditions.
AB  - Dispersing micronized fat crystals (MFCs) in oil is a novel route to largely
      decouple fat crystallisation and network formation and thus to simplify the
      manufacture of fat-continuous food products. MFCs dispersed in oil form a weak
      interaction network organized by crystal aggregates in a continuous net of
      crystalline nanoplatelets. The rough surface of MFC nanoplatelets hampers
      stacking into one-dimensional aggregates, which explains the high mass fractal
      dimensions of the networks formed in MFC dispersions. Applying shear does not
      have a significant effect on the fractal dimensions of MFC networks, and MFC
      aggregates in the range of 5-10 MUm remain intact. However, shear leads to a
      significant loss of storage modulus and yield stress over a time frame of an
      hour. This can be attributed to irreversible disruption of the continuous net of
      nanoplatelets. Rheo-SAXS revealed that shear releases nanoplatelets from the
      continuous net, which subsequently align in the shear field and undergo rapid
      recrystallisation. The release of thin and metastable nanoplatelets from the weak
      link network bears relevance for simplified and more effective manufacturing of
      emulsified food products by effectively decoupling crystallisation, network
      formation and emulsification.

PMID- 29634055
TI  - Confined co-assembly of AB/BC diblock copolymer blends under 3D soft confinement.
AB  - Compared to synthesizing a new block copolymer, blending of two types of block
      copolymers or a block copolymer and a homopolymer is a simple yet effective
      approach to create new self-assembled nanostructures. Here, we apply Monte Carlo
      (MC) simulations to mimic the co-assembly of AB/BC diblock copolymer blends
      within a three-dimensional (3D) soft confined space, which corresponds to the co
      assembly confined in an emulsion droplet in experiment. The confined co
      assemblies of four types of block copolymer blends at different block ratios,
      i.e., A8B8/B8C8, A6B10/B10C6, A12B4/B4C12 and A12B4/B10C6, are investigated by MC
      simulations. The simulation results reveal that the ratio of different types of
      blocks and the polymer-solvent interactions between the different blocks and the
      solvent determine the final self-assembled nanostructures. By tailoring these two
      controlling parameters, we not only reproduced some classic nanostructures, i.e.,
      pupa-, onion-, and bud-like particles, but also predicted some unconventional
      nanostructures, such as patch-, Janus-, peanut-, disc- and snowman-like particles
      via MC simulations.

PMID- 29634056
TI  - Noncompetitive homogeneous immunodetection of small molecules based on beta
      glucuronidase complementation.
AB  - In this study, a novel noncompetitive homogeneous immunoassay for antigen
      detection was developed. We utilized beta-glucuronidase (GUS), a homotetrameric
      enzyme, the assembly of all of whose subunits is necessary to attain its
      activity. By using a mutant GUS (GUSm), wherein the dimerization of dimers, which
      is a rate-limiting step, can be effectively inhibited by a set of interface
      mutations, we attempted to create a biosensor for detecting various molecules.
      Usually, the affinity between the two variable region domains (VH and VL) of an
      antibody, especially for a small molecule, is relatively low. However, in the
      presence of an antigen, the affinity increases so that they bind tighter to each
      other. A pair of fusion proteins, comprising the VH and VL regions of the
      antibody as the detector tethered to a GUSm subunit as the reporter, was
      constructed to detect antigen 4-hydroxy-3-nitrophenylacetyl (NP) and bone Gla
      protein (BGP) through GUS activity measurement. Colorimetric and fluorescence
      assays could detect NP, 5-iodo-NP, and BGP within 1 h without separation steps
      and with a higher signal/background ratio than conventional ELISA. The
      instantaneous response after simple mixing of the components makes this system
      convenient and high-throughput. The system could be effective for the analyses of
      various small molecules in environmental and clinical settings.

PMID- 29634057
TI  - Formal synthesis of cis-solamin: acid-catalyzed one-step construction of 2,5
      disubstituted tetrahydrofuran.
AB  - A divergent strategy has been used for the concise and efficient enantioselective
      formal synthesis of Annonaceous acetogenin cis-solamin. Our synthetic strategy
      comprises concise preparation of the diepoxyester via an 11-membered silaketal
      constructed by ring-closing metathesis after the dimerization of chiral epoxides,
      and uses an acid-catalyzed tandem intramolecular SN2-like reaction to construct
      the threo-cis-threo configuration of the tetrahydrofuran-diol moiety.

PMID- 29634058
TI  - A highly efficient dual-diazonium reagent for protein crosslinking and
      construction of a virus-based gel.
AB  - A new bench-stable reagent with double diazonium sites was designed and
      synthesized for protein crosslinking. Based on the highly efficient diazonium-Tyr
      coupling reaction, a direct mixture of the reagent and tobacco mosaic virus led
      to the formation of a new hydrogel, which could be degraded by chemicals and
      could be used to encapsulate small molecules for sustained release. Because plant
      viruses exhibit many chemical characteristics like protein labelling and nucleic
      acid packaging, the virus-based hydrogel will have large chemical space for
      further functionalization. Besides, this dual-diazonium reagent should be a
      generally useful crosslinker for chemical biology and biomaterials.

PMID- 29634059
TI  - Decomposition of methanol-d4 on Au-Rh bimetallic nanoclusters on a thin film of
      Al2O3/NiAl(100).
AB  - The decomposition of methanol-d4 that was adsorbed on Au-Rh bimetallic
      nanoclusters grown by the sequential deposition of Au and Rh vapors onto ordered
      thin-film Al2O3/NiAl(100) at 300 K, occurred by means of dehydrogenation and
      primarily on the surface Rh. Nevertheless, the surface Rh atoms were not equally
      reactive; their reactivity altered with both structural and electronic effects
      arising from the alloying. The Au deposited on Rh clusters decorated the surface
      and deactivated Rh by not only directly obstructing them but also by neighboring
      them. As the initially incorporated Au tended to aggregate around reactive low
      coordinated Rh atoms, such as corner Rh atoms, the reactivity of the cluster,
      indicated by the CO and deuterium (D2) produced per surface Rh, decreased
      markedly. In contrast, the Rh deposited on Au clusters promoted their reactivity.
      The reactivity was sharply enhanced by a few incorporated Rh atoms, as they
      preferentially decorated the edge Au atoms, resulting in their lower
      coordination, more positive charge, higher energetic d-band centers, and high
      reactivity. On the reactive Rh, the scission of the O-D bond in the initial
      dehydrogenation of methanol-d4 became more preferential than the competing
      desorption. The further incorporated Rh failed to promote the reactivity, but the
      clusters remained more reactive than those formed by Rh clusters incorporating Au
      as their structuring involved an active atomic segregation that yielded more low
      coordinated and reactive surface Rh.

PMID- 29634060
TI  - Synthesis, characterization, and cytotoxic properties of mono- and di-nuclear
      cobalt(ii)-polypyridyl complexes.
AB  - We report the synthesis and characterisation of mono- and di-nuclear cobalt(ii)
      complexes (1-3) containing L1, a polypyridyl ligand with pyrazole moieties. DNA
      binding studies suggest that the mono-nuclear complex, 1, binds to DNA via the
      grooves prior to inducing oxidative DNA cleavage whereas the larger di-nuclear
      complexes, 2 and 3, bind to DNA via the grooves and through intercalation prior
      to inducing oxidative DNA cleavage. The cobalt(ii) complexes display micromolar
      potency towards U2OS (bone osteosarcoma), HepG2 (liver hepatocellular carcinoma),
      and GM05757 (normal human fibroblast) cells, comparable to clinically used
      platinum agents, cisplatin and carboplatin. The cellular mechanism of action
      studies show that the most effective cobalt(ii) complex, 2, enters U2OS cells,
      penetrates the nucleus, induces genomic DNA damage, and triggers caspase
      dependent apoptosis in a p53-independent manner. This study highlights the
      potential of di-nuclear cobalt(ii) complexes as artificial oxidative
      metallonucleases and tangible cancer cell-potent agents.

PMID- 29634061
TI  - Direct growth of 2D nickel hydroxide nanosheets intercalated with polyoxovanadate
      anions as a binder-free supercapacitor electrode.
AB  - A mesoporous nanoplate network of two-dimensional (2D) layered nickel hydroxide
      Ni(OH)2 intercalated with polyoxovanadate anions (Ni(OH)2-POV) was built using a
      chemical solution deposition method. This approach will provide high flexibility
      for controlling the chemical composition and the pore structure of the resulting
      Ni(OH)2-POV nanohybrids. The layer-by-layer ordered growth of the Ni(OH)2-POV is
      demonstrated by powder X-ray diffraction and cross-sectional high-resolution
      transmission electron microscopy. The random growth of the intercalated Ni(OH)2
      POV nanohybrids leads to the formation of an interconnected network morphology
      with a highly porous stacking structure whose porosity is controlled by changing
      the ratio of Ni(OH)2 and POV. The lateral size and thickness of the Ni(OH)2-POV
      nanoplates are ~400 nm and from ~5 nm to 7 nm, respectively. The obtained thin
      films are highly active electrochemical capacitor electrodes with a maximum
      specific capacity of 1440 F g-1 at a current density of 1 A g-1, and they
      withstand up to 2000 cycles with a capacity retention of 85%. The superior
      electrochemical performance of the Ni(OH)2-POV nanohybrids is attributed to the
      expanded mesoporous surface area and the intercalation of the POV anions. The
      experimental findings highlight the outstanding electrochemical functionality of
      the 2D Ni(OH)2-POV nanoplate network that will provide a facile route for the
      synthesis of low-dimensional hybrid nanomaterials for a highly active
      supercapacitor electrode.

PMID- 29634062
TI  - Expanding antibiotic chemical space around the nidulin pharmacophore.
AB  - Reinvestigating antibiotic scaffolds that were identified during the Golden Age
      of antibiotic discovery, but have long since been "forgotten", has proven to be
      an effective strategy for delivering next-generation antibiotics capable of
      combatting multidrug-resistant superbugs. In this study, we have revisited the
      trichloro-substituted depsidone, nidulin, as a selective and unexploited
      antibiotic lead produced by the fungus Aspergillus unguis. Manipulation of halide
      ion concentration proved to be a powerful tool for modulating secondary
      metabolite production and triggering quiescent pathways in A. unguis.
      Supplementation of the culture media with chloride resulted in a shift in co
      metabolite profile to dichlorounguinols and nornidulin at the expense of the non
      chlorinated parent, unguinol. Surprisingly, only marginal enhancement of nidulin
      was observed, suggesting O-methylation may be rate-limiting. Similarly,
      supplementation of the media with bromide led to the production of the
      corresponding bromo-analogues, but also resulted in a novel family of depsides,
      the unguidepsides. Unexpectedly, depletion of chloride from the media halted the
      biosynthesis of the non-chlorinated parent compound, unguinol, and redirected
      biosynthesis to a novel family of ring-opened analogues, the unguinolic acids.
      Supplementation of the media with a range of unnatural salicylic acids failed to
      yield the corresponding nidulin analogues, suggesting the compounds may be
      biosynthesised by a single polyketide synthase. In total, 12 new and 11
      previously reported nidulin analogues were isolated, characterised and assayed
      for in vitro activity against a panel of bacteria, fungi and mammalian cells,
      providing a comprehensive structure-activity profile for the nidulin scaffold.

PMID- 29634063
TI  - A simple and sensitive detection of small molecule-protein interactions based on
      terminal protection-mediated exponential strand displacement amplification.
AB  - We herein describe a simple and sensitive strategy to detect a small molecule
      protein interaction based on terminal protection-mediated exponential strand
      displacement amplification (eSDA). In principle, the small molecule linked to a
      DNA probe protects the DNA probe against the exonuclease I-catalyzed degradation
      after its binding to the corresponding target protein. The protected DNA probe
      then serves as a template to promote eSDA. Consequently, a large number of
      duplexes are produced, which leads to a high fluorescence from a double-stranded
      DNA specific fluorescent dye, SYBR Green I. As a model system to prove this
      sensing strategy, the interaction between biotin and streptavidin (SA), which is
      known to be the strongest among the non-covalent biological interactions, was
      selected and its analytical performance was thoroughly investigated. As a result,
      SA was sensitively detected with the limit of detection of 16 pM. In addition,
      the practical applicability of this method was successfully demonstrated by
      reliably determining the SA in human serum.

PMID- 29634064
TI  - Ca-Tetrafluorophthalate and Sr-isophthalate: mechanochemical synthesis and
      characterization in comparison with other Ca-and Sr-coordination polymers.
AB  - New Ca- and Sr-based coordination polymers (CPs) were mechanochemically
      synthesized by milling metal hydroxide samples (M = Ca, Sr) with
      tetrafluorophthalic acid (H2oBDC-F4) and isophthalic acid (H2mBDC). [Ca(oBDC
      F4)(H2O)2] (1) exhibits a small surface area which is slightly increased after
      removing the crystal water. On the other hand, the hydrated sample of the
      nonfluorinated [Sr(mBDC)(H2O)3.4] (2) reveals a small BET surface area which
      remains unchanged even after the release of crystal water via thermal treatment.
      The new compounds 1 and 2 are similar to their Sr- and Ca-analogs, respectively.
      These findings are confirmed by thermal analysis, MAS NMR, and ATR-IR
      measurements, in addition to the Le Bail refinements for the measured powder X
      ray data of 1 and 2. Ca- and Sr-CPs based on perfluorinated dicarboxylic systems
      and their nonfluorinated analogs diverse in structural and chemical properties
      depending on the geometries of the organic linkers and the presence of fluorine
      atoms. The fluorinations of organic ligands lead to the formation of fluorinated
      CPs with higher dimensionalities compared to their nonfluorinated counterparts.
      Conversely, the thermal stabilities of the latter are higher than those of the
      fluorinated CPs.

PMID- 29634065
TI  - Super electron donor-mediated reductive transformation of nitrobenzenes: a novel
      strategy to synthesize azobenzenes and phenazines.
AB  - The transformation of nitrobenzenes into azobenzenes by pyridine-derived super
      electron donor 2 is described. This method provides an efficient synthesis of
      azobenzenes because of not requiring the use of expensive transition-metals,
      toxic or flammable reagents, or harsh conditions. Moreover, when using 2
      fluoronitrobenzenes as substrates, phenazines were found to be obtained. The
      process affords a novel synthesis of phenazines.

PMID- 29634066
TI  - Design and synthesis of novel monoterpenoid indole alkaloid-like analogues and
      their antitumour activities in vitro.
AB  - A biomimetic synthetic strategy and combinatorial chemistry were used to
      synthesize 34 novel monoterpenoid indole alkaloid (MIA) analogues, and their
      cytotoxic activities against five cancer cell lines (SW-480, A-549, HL-60, SMMC
      7721, and MCF-7) were determined using the 3-(4,5-dimethylthiazol-2-yl)-5-(3
      carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. Fourteen of
      these analogues (7, 16-18, and 23-32) showed significantly greater inhibition of
      tumour cell proliferation than cisplatin. Compounds 17 and 18 showed the highest
      cytotoxic activity against the HL-60 cell line with IC50 values of 0.90 MUM and
      0.43 MUM, respectively. Compound 18 slightly induced apoptosis and arrested the
      cell cycle in SW-480, A-549, HL-60, SMMC-7721, and MCF-7 cells. Analysis of the
      primary structure-activity relationships reveals that the introduction of
      different substituent groups at the C-3, C-5, and C-6 positions of the indole
      moiety and the C-10 position of the genipin moiety might have an effect on the
      antitumour activity of the resulting compounds.

PMID- 29634068
TI  - ?

PMID- 29634067
TI  - Hierarchically structured iron-doped silver (Ag-Fe) lotus flowers for an
      efficient oxygen reduction reaction.
AB  - The development of cheap and efficient electrocatalysts for the oxygen reduction
      reaction (ORR) is vital for the immediate commercialization of fuel cells which
      are still limited by the high cost and low performance of the utilized commercial
      Pt-based electrodes. As a promising alternative, this study reports on the
      synthesis of hierarchical iron-doped silver lotus flowers (AgFelotus) by a facile
      chemical procedure as robust and efficient ORR electrocatalysts. Succinic acid
      was used as a structure directing agent to tune the morphology of undoped and
      iron-doped silver particles. In the absence of succinic acid, ball-like silver
      particles were obtained, while using 2 mM succinic acid led to peony-like flower
      structures. The doping of silver peony-flowers with iron resulted in lotus-like
      flower structures with high electrocatalytic activity for ORR together with
      outstanding tolerance against poisoning with various hydrocarbon (HC) impurities,
      in situ generated during fuel cell operation, as well as different fuels from
      anodic crossover. AgFelotus exhibited a superior ORR activity with more than 40
      times higher stability than the commercial Pt/C catalyst in alkaline media. This
      substantial performance enhancement is attributed to the unique lotus-like flower
      structures providing more electroactive surface sites, in addition to the iron
      dopants which facilitate ORR charge transfer.

PMID- 29634069
TI  - ?

PMID- 29634070
TI  - ?

PMID- 29634071
TI  - [<p>One steroid injection in combination with HIV-medication resulted in a total
      adrenal insufficiency</p>].
AB  - This case report describes a woman living with HIV on treatment including
      ritonavir-boosted darunavir, who suffered complete secondary adrenal
      insufficiency after a single intra-articular injection of the corticosteroid
      triamcinolone. There is a known pharmacological interaction between ritonavir and
      those corticosteroids which are metabolised by the CYP3A4 pathway. This
      interaction may lead to complete adrenal insufficiency, which is a life
      threatening condition. Adrenal insufficiency must be promptly diagnosed and
      hydrocortisone replacement started. People living with HIV should be on lifelong
      antiretroviral treatment, and corticosteroids are common in the treatment of many
      different conditions seen by various specialists. This case highlights that not
      only physicians engaged in HIV treatment need to be aware of this important
      interaction.

PMID- 29634073
TI  - ?

PMID- 29634072
TI  - [Treatment with metformin in type 2 diabetes mellitus - new routines when renal
      function is reduced and in connection with administration of iodine contrast
      media].
AB  - Metformin is eliminated through glomerular filtration and tubular secretion in
      the kidneys. New guidelines recommend use of metformin down to a GFR of 30 mL/min
      under the condition that the dose is adjusted. As the risk of inducing lactic
      acidosis is very low in connection with administration of iodine contrast media,
      new recommendations in Sweden say that metformin must be stopped only when GFR is
      below 45 mL/min. Determination of metformin levels in serum is useful to guide
      therapeutic dose when GFR is low but also to confirm that lactic acidosis is
      caused by metformin.

PMID- 29634074
TI  - ?

PMID- 29634075
TI  - ?

PMID- 29634076
TI  - Surgically Treated Status Epilepticus due to Large Cortical Tuber and Long-Term
      Follow-Up Results.
AB  - We present a case of invasive monitoring of a patient while he was being
      surgically treated in the status state. Our patient was a 27-year-old male who
      was hospitalized for frequent seizures, which began after a head trauma at the
      age of 3. Video electroencephalography was performed, and 25 clinical seizures
      were observed in 24 h. Cranial magnetic resonance imaging revealed a T2
      hyperintense and T1 hypointense lesion at the right frontal lobe and subependymal
      nodule. For the purpose of invasive monitoring, subdural electrodes were placed
      on the cortex surface via a right frontal craniotomy. The patient was reoperated,
      and epileptic zone resection was performed. There was no sign of neurological
      deficit. Histopathological examination revealed cortical tuber, and the patient
      was scanned for tuberous sclerosis. There was no sign of tuberous sclerosis in
      other organs. Our patient was diagnosed with tuberous sclerosis, cortical tuber,
      subependymal nodule, epilepsy, and intermediate mental retardation. Radiological
      diagnosis should also be considered. Cortical tuber can be confused with focal
      cortical dysplasia. Finally, staged resection may be necessary for surgical
      treatment in some cases.

PMID- 29634077
TI  - The Predictor Role of the Aqueduct Cerebrospinal Fluid Flow on Endoscopic Third
      Ventriculostomy: Explication on Assumption Physical Model.
AB  - AIM: To evaluate the cerebrospinal fluid (CSF) flow dynamics in the aqueductus
      sylvii of patients with obstructive hydrocephalus who underwent endoscopic third
      ventriculostomy (ETV) and to predict ventriculostomy patency via aqueduct flow
      measurements. MATERIAL AND METHODS: Twenty-four patients with obstructive
      hydrocephalus caused by primary aqueduct stenosis who underwent ETV were included
      in the study. All the patients underwent conventional and cine magnetic resonance
      imaging before and after treatment. The flow of CSF in the aqueduct of Sylvius
      and prepontine cistern was assessed, and the diameter of the third ventricle was
      also measured. Increase in the aqueduct flow velocity after a successful ETV was
      supported by the assumption physical model that highlights a possible mechanism
      that explains the clinical findings. RESULTS: The flow pattern and velocity in
      the prepontine cistern and aqueduct were normal in 17 out of 24 patients who
      responded to ETV clinically. However, seven patients who did not respond to ETV
      had an abnormal flow pattern in both the prepontine cistern and aqueduct.
      CONCLUSION: The flow pattern in the aqueduct was normalised and velocity was
      increased compared with those of preoperative values after a successful ETV. The
      flow of CSF in the prepontine cistern is routinely used for ventriculostomy
      patency assessment. In addition, aqueduct measurements may be useful in
      predicting ventriculostomy patency. The physical model provides valuable insights
      on a possible mechanism that affected the experimental data.

PMID- 29634078
TI  - Is temporary proximal artery clipping in AVM surgery safe?
AB  - AIM: Surgical excision of arteriovenous malformations (AVMs) still poses a
      challenge, with uncontrolled bleeding and brain swelling being dreaded
      intraoperative complications. The authors describe their experiences with
      surgical excision of cerebral AVMs using temporary proximal artery clipping to
      reduce intraoperative bleeding and excision time. MATERIAL AND METHODS: Temporary
      proximal artery clipping was employed by the authors during surgery on 14
      patients with cerebral AVMs in a public-sector institution. Seven AVMs were
      situated in eloquent areas like the sensory, motor, and speech areas and the
      other seven were located in non-eloquent areas. Four patients each were
      classified as Spetzler grades 2 and 4 while three patients each were classified
      as grades 3 and 5. A large craniotomy flap was fashioned to enable access to the
      proximal feeding arteries along with the AVM. After wide dural opening, the
      proximal feeding arteries were first approached. The proximal middle cerebral
      artery was approached by opening the proximal sylvian cistern, an
      interhemispheric approach was employed for the distal anterior cerebral artery,
      and a subtemporal route was used for the P2 portion of the posterior cerebral
      artery. After placing a temporary aneurysm clip on the proximal feeding artery,
      excision of the AVM was performed, employing the basic principles of AVM
      excision. RESULTS: Total excision of the AVM was achieved in all cases. There
      were no instances of cerebral infarction or neurological deficits attributable to
      temporary clipping of the proximal artery. There was no mortality in this series.
      CONCLUSION: Temporary proximal artery clipping helps in surgical excision by
      reducing intraoperative bleeding and resection time.

PMID- 29634079
TI  - Benign-appearing Intraspinal Malignant Peripheral Nerve Sheath Tumors: Treatments
      and Outcomes of 14 Consecutive Patients.
AB  - AIM: To investigate the clinical characteristics and prognostic factors that may
      influence outcomes of patients undergoing benignappearing intraspinal malignant
      peripheral nerve sheath tumors (MPNSTs). MATERIAL AND METHODS: This study
      included a total of 14 consecutive patients who were diagnosed with benign
      intraspinal tumors firstly and confirmed as intraspinal MPNSTs by pathology. The
      univariate analyses of various clinical factors were performed to identify
      variables that could predict prognosis. Endpoints were mortality and local
      recurrence. The survival rate was estimated using the Kaplan?Meier method, and
      differences were analyzed by carrying out the log-rank test. In addition, factors
      with p values of ?0.05 were considered statistically significant. RESULTS: Benign
      appearing intraspinal MPNSTs showed some different clinical features compared
      with spinal MPNSTs and intraspinal benign tumors. The present study found that
      age at diagnosis, Neurofibromatosis type 1 (NF-1) history, tumor sites, malignant
      grade, Ki-67 and tumor resection method might be factors closely associated with
      recurrence and survival of intraspinal MPNSTs patients. CONCLUSION: Benign
      appearing intraspinal MPNSTs are relatively rare tumors with a better overall
      prognosis compared with common spinal MPNSTs. A lot of factors can affect
      patients" survival and local recurrence. These prognostic factors still require
      further confirmation with further studies including more patients.

PMID- 29634080
TI  - Simpson Grade 2 Resection and Tumor Recurrence in Ventrally Located Spinal
      Meningiomas.
AB  - AIM: To evaluate postoperative clinical outcome and recurrence rates in cases
      with ventrally located spinal meningiomas who underwent Simpson grade 2
      resection. MATERIAL AND METHODS: We evaluated eight cases (six females and two
      males; age, 28?86 years; mean age, 60 years) with ventrally located spinal
      meningioma that underwent surgical treatment in our clinic. The tumors were
      located in the thoracic region in seven cases and in the cervical region in one
      case. All cases underwent surgery, which was performed using a traditional
      posterior midline approach. Laminectomy was unilaterally extended. The case with
      cervically located tumor differed from the other cases in that a skull clamp was
      used and laminoplasty was performed. RESULTS: The tumor was completely resected
      in all cases. Furthermore, in all cases, the tumor nidus that caused the
      thickening of the dura was cauterized using bipolar cautery and peeled off
      (Simpson grade 2). The pathological examination of the tumor specimens revealed
      typical grade 1 meningioma in all cases (fibropsammomatous type, n=1;
      meningothelial type, n=3; and psammomatous type, n=4). Recurrence was not
      observed in any of the cases during the follow-up. None of the cases demonstrated
      postoperative neurological deterioration. At 1 month postoperatively, pain and
      motor deficit completely improved in all cases, with remarkable improvements of
      motor deficits in the early postoperative period. CONCLUSION: Simpson grade 2
      resection in ventrally located spinal meningiomas results in low complication
      rates and is satisfactory in terms of recurrence.

PMID- 29634081
TI  - Assessing Aneurysm Obliteration and Neck Remnants in 225 Clipped Aneurysms Using
      Indocyanine Green Video Angiography, Micro-Doppler Ultrasonography and
      Postoperative Digital Subtraction Angiography.
AB  - AIM: To present our experience of 225 clipped aneurysms in 196 patients to
      compare indocyanine green video angiography (ICGVA), micro-Doppler
      ultrasonography (MDUSG), and postoperative digital subtraction angiography (DSA)
      in terms of determining aneurysm obliteration, neck remnants, and parent artery
      patency. MATERIAL AND METHODS: This retrospective study included 196 patients
      (108 female and 88 male patients) treated between 2013 and 2016. In all cases,
      aneurysm neck remnants and vessel patency were assessed using ICG-VA and 16-Hz
      MDUSG. DSA was performed in every case postoperatively within the first 5 days.
      RESULTS: The mean patient age was 55.8 years (range, 31-80 years), and the mean
      follow-up duration was 25 months (range, 2-48 months). Of the 225 clipped
      aneurysms, 86 were located in the anterior cerebral artery and its branches, 103
      in the bifurcation of the middle cerebral artery (MCA) and the branches of the
      MCA, 34 in the internal cerebral artery and its branches, 1 in the posterior
      inferior cerebellar artery, and 1 at the basilar apex. We observed 2 neck
      remnants (0.8%), 2 parent/perforating artery occlusions (0.8%), and 2 residual
      aneurysm fillings (0.8%). There were no striking differences among the assessed
      methods. CONCLUSION: ICG-VA, MDUSG, and dome puncturing are all useful techniques
      in aneurysm surgery for assessing complete obliteration of the aneurysm. In our
      experience, all the 3 tools are complementary to each other, and none of them is
      superior to the others. We recommend the use of all 3 tools to obtain a favorable
      outcome.

PMID- 29634082
TI  - The Preventative Effect of alpha-Tocopherol on Spinal Epidural Fibrosis After
      Laminectomy in a Rat Model.
AB  - AIM: Postlaminectomy epidural fibrosis is a major source of decreased quality of
      life after spinal surgery. Prevention of epidural fibrosis seems a logical way
      for avoiding of some uneventful effects and reoperation. Many chemicals used for
      prevention of epidural fibrosis up to this day. The aim of this study is to
      assess efficacy of alpha-tocopherol as a topical antifibrotic agent on epidural
      fibrosis for lumbar laminectomy procedures. MATERIAL AND METHODS: Thirty-two
      adults rats assigned into 4 groups, with 8 rats in each group were used in this
      study. Standard laminectomy was performed for every rat. The rats in group I no
      treatment after laminectomy was administered. The rats in Group II gelatin sponge
      was soaked alpha-tocopherol. The rats in Group III saline soaked absorbable
      gelatin sponge used and left on dura mater after laminectomy. And the rats in
      Group IV, only alpha-tocopherol were used on the dura mater after laminectomy.
      The an-bloc vertebral columns of the rats were removed after sacrificing between
      T10 and L5 in 30th postoperative day. Specimens were evaluated for degree of
      fibrosis and arachnoidal invasions. RESULTS: Statistical differences between the
      mean of fibrosis grades of groups were significant by a p value of 0.011. Between
      the mean of arachnoidal invasion of groups were not statistically significant (p
      0.05). CONCLUSION: This study proven that topical application of alpha-tocopherol
      could effectively reduce the development of epidural fibrosis in an experimental
      laminectomy model.

PMID- 29634083
TI  - Risperidone for psychosis-induced aggression or agitation (rapid
      tranquillisation).
AB  - BACKGROUND: Aggressive, agitated or violent behaviour due to psychosis
      constitutes an emergency psychiatric treatment where fast-acting interventions
      are required. Risperidone is a widely accessible antipsychotic that can be used
      to manage psychosis-induced aggression or agitation. OBJECTIVES: To examine
      whether oral risperidone alone is an effective treatment for psychosis-induced
      aggression or agitation. SEARCH METHODS: We searched the Cochrane Schizophrenia
      Group's Study-Based Register of Trials (up to April 2017); this register is
      compiled by systematic searches of major resources (including AMED, BIOSIS
      CINAHL, Embase, MEDLINE, PsycINFO, PubMed, and registries of clinical trials) and
      their monthly updates, handsearches, grey literature, and conference proceedings.
      There are no language, date, document type, or publication status limitations for
      inclusion of records into the register. SELECTION CRITERIA: Randomised controlled
      trials (RCTs) comparing rapid use of risperidone and other drugs, combinations of
      drugs or placebo for people exhibiting aggression or agitation (or both) thought
      to be due to psychosis. DATA COLLECTION AND ANALYSIS: We independently inspected
      all citations from searches, identified relevant abstracts, and independently
      extracted data from all included studies. For binary data we calculated risk
      ratio (RR) and for continuous data we calculated mean difference (MD), all with
      95% confidence intervals (CI) and used a fixed-effect model. We assessed risk of
      bias for the included studies and used the GRADE approach to produce a 'Summary
      of findings' tables. MAIN RESULTS: The review now contains data from nine trials
      (total n = 582) reporting on five comparisons. Due to risk of bias, small size of
      trials, indirectness of outcome measures and a paucity of investigated and
      reported 'pragmatic' outcomes, evidence was graded as very-low quality. None of
      the included studies provided useable data on our primary outcome
      'tranquillisation or asleep' by 30 minutes, repeated need for tranquillisation or
      any economic outcomes. Data were available for our other main outcomes of
      agitation or aggression, needing restraint, and incidence of adverse
      effects.Risperidone versus haloperidol (up to 24 hours follow-up)For the outcome,
      specific behaviour - agitation, no clear difference was found between risperidone
      and haloperidol in terms of efficacy, measured as at least 50% reduction in the
      Positive and Negative Syndrome Scale - Psychotic Agitation Sub-score (PANSS-PAS)
      (RR 1.04, 95% CI 0.86 to 1.26; participants = 124; studies = 1; very low-quality
      evidence) and no effect was observed for need to use restraints (RR 2.00, 95% CI
      0.43 to 9.21; participants = 28; studies = 1; very low-quality evidence).
      Incidence of adverse effects was similar between treatment groups (RR 0.94, 95%
      CI 0.54 to 1.66; participants = 124; studies = 1; very low-quality
      evidence).Risperidone versus olanzapineOne small trial (n = 29) reported useable
      data for the comparison risperidone versus olanzapine. No effect was observed for
      agitation measured as PANSS-PAS endpoint score at two hours (MD 2.50, 95% CI 
      2.46 to 7.46; very low-quality evidence); need to use restraints at four days (RR
      1.43, 95% CI 0.39 to 5.28; very-low quality evidence); specific movement
      disorders measured as Behavioural Activity Rating Scale (BARS) endpoint score at
      four days (MD 0.20, 95% CI -0.43 to 0.83; very low-quality evidence).Risperidone
      versus quetiapineOne trial reported (n = 40) useable data for the comparison
      risperidone versus quetiapine. Aggression was measured using the Modified Overt
      Aggression Scale (MOAS) endpoint score at two weeks. A clear difference,
      favouring quetiapine was observed (MD 1.80, 95% CI 0.20 to 3.40; very-low quality
      evidence). No evidence of a difference between treatment groups could be observed
      for incidence of akathisia after 24 hours (RR 1.67, 95% CI 0.46 to 6.06; very low
      quality evidence). Two participants allocated to risperidone and one allocated to
      quetiapine experienced myocardial ischaemia during the trial.Risperidone versus
      risperidone + oxcarbazepineOne trial (n = 68) measured agitation using the
      Positive and Negative Syndrome Scale - Excited Component.(PANSS-EC) endpoint
      score and found a clear difference, favouring the combination treatment at one
      week (MD 2.70, 95% CI 0.42 to 4.98; very low-quality evidence), but no effect was
      observed for global state using Clinical Global Impression - Improvement (CGI-I)
      endpoint score at one week (MD -0.20, 95% CI -0.61 to 0.21; very-low quality
      evidence). Incidence of extrapyramidal symptoms after 24 hours was similar
      between treatment groups (RR 1.59, 95% CI 0.49 to 5.14; very-low quality
      evidence).Risperidone versus risperidone + valproic acidTwo trials compared
      risperidone with a combination of risperidone plus valproic acid. No clear
      differences between the treatment groups were observed for aggression (MOAS
      endpoint score at three days: MD 1.07, 95% CI -0.20 to 2.34; participants = 54;
      studies = 1; very low-quality evidence) or incidence of akathisia after 24 hours:
      RR 0.75, 95% CI 0.28 to 2.03; participants = 122; studies = 2; very low-quality
      evidence). AUTHORS' CONCLUSIONS: Overall, results for the main outcomes show no
      real effect for risperidone. The only data available for use in this review are
      from nine under-sampled trials and the evidence available is of very low quality.
      This casts uncertainty on the role of risperidone in rapid tranquillisation for
      people with psychosis-induced aggression. High-quality pragmatic RCTs are
      feasible and are needed before clear recommendations can be drawn on the use of
      risperidone for psychosis-induced aggression or agitation.

PMID- 29634084
TI  - Out of the shadows and 6000 reasons to celebrate: An update from FIGO's fistula
      surgery training initiative.
AB  - Obstetric fistula is a devastating childbirth injury caused by unrelieved
      obstructed labor. Obstetric fistula leads to chronic incontinence and, in most
      cases, significant physical and emotional suffering. The condition continues to
      blight the lives of 1-2 million women in low-resource settings, with 50 000-100
      000 new cases each year adding to the backlog. A trained, skilled fistula surgeon
      is essential to repair an obstetric fistula; however, owing to a global shortage
      of these surgeons, few women are able to receive life-restoring treatment. In
      2011, to address the treatment gap, FIGO and partners released the Global
      Competency-Based Fistula Surgery Training Manual, the first standardized
      curriculum to train fistula surgeons. To increase the number of fistula surgeons,
      the FIGO Fistula Surgery Training Initiative was launched in 2012, and FIGO
      Fellows started to enter the program to train as fistula surgeons. Following a
      funding boost in 2014, the initiative has grown considerably. With 52 fellows
      involved and a new Expert Advisory Group in place, the program is achieving major
      milestones, with a record-breaking number of fistula repairs performed by FIGO
      Fellows in 2017, bringing the total number of repairs since the start of the
      project to more than 6000.

PMID- 29634085
TI  - Binge Drinking Above and Below Twice the Adolescent Thresholds and Health-Risk
      Behaviors.
AB  - BACKGROUND: Underage drinking has been associated with health-risk behaviors:
      unintentional and unprotected sex; physical and sexual assault; suicide;
      homicide; traffic and other unintentional injuries; and overdoses. Five drinks
      consumed over 2 hours by adult males and 4 drinks by adult females typically
      produce blood alcohol levels (BALs) of >=0.08%, which the National Institute on
      Alcohol Abuse and Alcoholism considers binge drinking. Being smaller, young
      adolescents can reach adult binge-drinking BALs of >=0.08% with fewer drinks.
      Previous research indicates boys ages 9 to 13 would reach >=0.08% with 3 drinks,
      4 drinks at ages 14 to 15, and 5 drinks at ages >=16. For girls, >=0.08% is
      reached with >=3 drinks at ages 9 to 17 and >=4 drinks at ages >=18. This study
      explores whether, among a national sample of high school students, adolescent
      binge drinking at >=twice versus <twice the age-/gender-specific thresholds
      versus nonbinge drinking heightens associations of drinking with health-risk
      behaviors. METHODS: In 2015, the Youth Risk Behavior Survey asked a national
      probability sample of 15,624 high school students grades 9 to 12 (response rate
      60%) about their past-month drinking and past-month or past-year health-risk
      behaviors. Logistic regressions with pairwise comparisons examined the
      association between different drinking levels and selected risk behaviors,
      adjusting for age, sex, race/ethnicity, and drinking frequency. RESULTS: Seven
      percent binged >=twice and 9% <twice the age-/gender-specific thresholds, and 14%
      drank less than the binge thresholds. Significantly higher percentages of binge
      drinkers at >=twice versus <twice the thresholds versus other drinkers reported
      illegal drug and tobacco use, risky sexual and traffic behaviors, physical
      fights, suicide, less school-night sleep, and poorer school grades. CONCLUSIONS:
      Adolescent alcohol misuse screening should query the maximum number of drinks
      consumed per occasion and frequency of such consumption. State and national
      surveillance surveys should include those questions to investigate which
      individual, family, school, community, and policy interventions reduce
      consumption beyond binge thresholds and related health-risk behaviors.

PMID- 29634086
TI  - Strong Hearts, Healthy Communities: A Community-Based Randomized Trial for Rural
      Women.
AB  - OBJECTIVE: The aim of this study was to evaluate a multilevel cardiovascular
      disease (CVD) prevention program for rural women. METHODS: This 6-month,
      community-based, randomized trial enrolled 194 sedentary rural women aged 40 or
      older with BMI >= 25 kg/m2 . Intervention participants attended 6 months of twice
      weekly exercise, nutrition, and heart health classes (48 total) that included
      individual-, social-, and environment-level components. An education-only control
      program included didactic healthy lifestyle classes once a month (six total). The
      primary outcome measures were change in BMI and weight. RESULTS: Within-group and
      between-group multivariate analyses revealed that only intervention participants
      decreased BMI (-0.85 units; 95% CI: -1.32 to -0.39; P = 0.001) and weight (-2.24
      kg; 95% CI: -3.49 to -0.99; P = 0.002). Compared with controls, intervention
      participants decreased BMI (difference: -0.71 units; 95% CI: -1.35 to -0.08; P =
      0.03) and weight (1.85 kg; 95% CI: -3.55 to -0.16; P = 0.03) and improved C
      reactive protein (difference: -1.15 mg/L; 95% CI: -2.16 to -0.15; P = 0.03) and
      Simple 7, a composite CVD risk score (difference: 0.67; 95% CI: 0.14 to 1.21; P =
      0.01). Cholesterol decreased among controls but increased in the intervention
      group (-7.85 vs. 3.92 mg/dL; difference: 11.77; 95% CI: 0.57 to 22.96; P = 0.04).
      CONCLUSIONS: The multilevel intervention demonstrated modest but superior and
      meaningful improvements in BMI and other CVD risk factors compared with the
      control program.

PMID- 29634088
TI  - Annual clinical updates in hematological malignancies: a continuing medical
      education series.

PMID- 29634087
TI  - Magnetic fibrinolysis: putting the therapeutic wheels in a corkscrew motion.

PMID- 29634089
TI  - Masked polycythemia Vera (mPV): Results of an international study.

PMID- 29634090
TI  - Hodgkin lymphoma: 2018 update on diagnosis, risk-stratification, and management.
AB  - DISEASE OVERVIEW: Hodgkin lymphoma (HL) is an uncommon B-cell lymphoid malignancy
      affecting 8500 new patients annually and representing approximately 10.2% of all
      lymphomas in the United States. DIAGNOSIS: HL is composed of two distinct disease
      entities: classical HL and nodular lymphocyte predominant HL. Nodular sclerosis,
      mixed cellularity, lymphocyte depletion, and lymphocyte-rich HL are subgroups of
      classical HL. RISK STRATIFICATION: An accurate assessment of the stage of disease
      in patients with HL is critical for the selection of the appropriate therapy.
      Prognostic models that identify patients at low or high risk for recurrence, as
      well as the response to therapy as determined by positron emission tomography
      scan, are used to optimize therapy. RISK-ADAPTED THERAPY: Initial therapy for HL
      patients is based on the histology of the disease, the anatomical stage and the
      presence of poor prognostic features. Patients with early stage disease are
      typically treated with combined modality strategies utilizing abbreviated courses
      of combination chemotherapy followed by involved-field radiation therapy, while
      those with advanced stage disease receive a longer course of chemotherapy often
      without radiation therapy. Newer agents including brentuximab vedotin are now
      being incorporated into frontline therapy and these new combinations are becoming
      a standard of care. MANAGEMENT OF RELAPSED/REFRACTORY DISEASE: High-dose
      chemotherapy (HDCT) followed by an autologous stem cell transplant (ASCT) is the
      standard of care for most patients who relapse following initial therapy. For
      patients who fail HDCT with ASCT, brentuximab vedotin, PD-1 blockade,
      nonmyeloablative allogeneic transplant or participation in a clinical trial
      should be considered.

PMID- 29634091
TI  - Prenatal screening for atypical chromosomal abnormalities: past or future?

PMID- 29634092
TI  - Re: First-trimester risk assessment based on ultrasound and cell-free DNA vs
      combined screening: a randomized controlled trial. K. O. Kagan, R. Sroka, J.
      Sonek, H. Abele, K. Luthgens, M. Schmid, P. Wagner, S. Brucker, D. Wallwiener and
      M. Hoopmann. Ultrasound Obstet Gynecol 2018; 51: 437-444.

PMID- 29634093
TI  - PELLETS AND PELLETIZATION: EMERGING TRENDS IN THE PHARMA INDUSTRY.
AB  - The present time is considered as an era of advancements in drug delivery
      systems. Different novel approaches are under investigation that range from
      uniparticulate to multi particulate system, macro to micro and nano particulate
      systems. Pelletization is one of the novel drug delivery technique that provides
      an effective way to deliver the drug in modified pattern. It is advantageous in
      providing site specific delivery of the drug. Drugs with unpleasant taste, poor
      bioavailability and short biological half-life can be delivered efficiently
      through pellets. Their reduced size makes them more valuable as compared to the
      conventional drug deliv- ery system. Different techniques are used to fabricate
      the pellets such as extrusion and spheronization, hot melt extrusion, powder
      layering, suspension or solution layering, freeze pelletization and pelletization
      by direct compression method. Various natural polymers including xanthan gum,
      guar gum, tragacanth and gum acacia, semisynthetic polymers like cellulose
      derivatives, synthetic polymers like derivatives of acrylamides, can be used in
      pellets formulation. Information provided in this review is collected from
      various national and intemational research articles, review articles and
      literature available in the books. The purpose of the current review is to
      discuss pellets, their characterizations, different techniques of pelletization
      and the polymers with potential of being suitable for pellets formulation.

PMID- 29634094
TI  - VITAMIN D IN ALZHEIMER'S DISEASE - PROPHYLAXIS OR THERAPY?.
AB  - The pleiotropism of vitamin D is due to the presence of vitamin D receptor in the
      cells of nearly all tissues and organs within the human body, including the CNS.
      Multiple evidence is available to support neuroprotective properties of vitamin
      D. These include, for example, the presence of 25(OH)D-lot-hydroxylase, an enzyme
      responsible for production of calcitriol, within the human brain. Among its other
      activities, calcitriol modifies production and release of neurotrophic factors,
      affects expression of genes associated with GABAergic signaling and stimulates
      biosynthesis of catecholamines. Antioxidative and anti-inflammatory properties
      were also demonstrated in research studies. By confronting the known
      pathomechanisms of Alzheimer's disease (AD) and the mechanism of action of
      vitamin D, one may propose that systemic insufficiency of vitamin D is a
      potential risk factor of AD. Studies conducted to date confirm the inverse
      relationship between serum calcidiol levels and the risk of dementia diseases,
      including AD. Elevated cerebrospinal fluid level of VDBP, a vitamin D binding
      protein that is also responsible for elimination of P-amyloid peptide (AP), a
      pathogenic factor characteristic for AD, is considered to be a potential marker
      of AD. Reduction in AP levels within the CNS is the most important therapeutic
      target in the treatment of AD. Animal studies confirmed the impact of vitamin D
      enriched diet on the reduction in amyloid deposits, AP peptide levels and
      inflammatory reactions as well as on the increase in the level of neurotrophic
      factor within the brains of AP protein precursor (APPP) - transgenic mice. In
      case of AD, the purposefulness of initiating treatment before the onset of
      clinical symptoms is being highlighted. Vitamin D is worth consideration since by
      inducing the expression of VDR gene it leads, among others, to the silencing of
      the transcription of the gene encoding the AOAPP and thus inhibits its cleavage
      into peptides that form amyloid deposits. Despite the fact that at current state
      vitamin D can hardly be considered a therapeutic agent with an established
      efficient dose in AD, authors of studies suggest that it is important in AD
      prophylaxis in elderly patients with age-related reduction of serum calcidiol lev
      els.

PMID- 29634096
TI  - FREE RADICAL FORMATION IN ROSUVASTATIN DURING THERMAL STERILIZATION AT DIFFERENT
      TEMPERATURES.
AB  - Rosuvastatin was thermally sterilized at temperatures 1600C during 120 min, 1700C
      during 60 min and 1800C during 30 min, according to Polish pharmacopoeia norms.
      Free radicals formed in the heated rosuvastatin samples were examined by electron
      paramagnetic resonance (EPR) spectroscopy. The best conditions of thermal
      sterilization of rosuvastatin were searched. EPR spectra were measured for the
      analyzed drug independent on heating temperature. Decrease of free radical
      concentrations in rosuvastatin with increasing of heating temperature was stated.
      The optimal conditions for thermal sterilization of rosuvastatin were temperature
      1800C and heating time of 30 min and resulted in the lowest free radical
      concentration. The changes of amplitudes (A) and linewidths (?Bpp) of EPR spectra
      of the heated rosuvastatin were characteristic for homogeneous broadening EPR
      lines. Slow spin-lattice relaxation processes existed in the all rosuvastatin
      samples. The confirmation of usefulness of electron paramagnetic resonance
      spectroscopy in pharmacy was presented.

PMID- 29634095
TI  - VORTIOXETINE - THE NEW ANTIDEPRESSANT AGENT WITH PROCOGNITIVE PROPERTIES.
AB  - Depression symptoms resulting from cognitive function impairment are emphasized
      by both DSM-5 and ICD-10 diagnostic criteria for major depressive disorder and
      depressive episodes. Nonetheless, the role of cognitive dysfunctions seem to
      remain underestimated in case of depressive disorders, thus they are rarely
      perceived as therapeutic target. Vortioxetine is a relatively new, multi
      functional agent. With its unique properties and strong affinity towards
      serotonin transporter (5-HTT), vortioxetine is a modulator and stimulator of
      serotonergic transmission. Vortioxetine is an antidepressant drug suitable for
      therapy in various types of depression: severe, anxiety-associated, and of
      elders. It acts equally strong as SNRIs or agomelatine and has favorable effects
      on cognitive functioning. Although vortioxetine has not undergone comprehensive
      preclinical testing, the available data indicate that this particular agent may
      be more advantageous in terms of its procognitive effects, as compared to other
      drugs - which often seemed to be analogous in preclinical and clinical testing.
      In vitro examination of hippocampal pyramidal cells revealed that vortioxetine
      improves both synaptic transmission and neuroplasticity responsible for memory
      and learning patterns. Contrary to fluoxetine, the long-term treatment with use
      of vortioxetine on mice resulted in enhanced visual and spatial memory, along
      with reduced occurrence of typical depressive behavior. In addition, vortioxetine
      is a very first drug efficiently augmenting cognitive function in adults
      diagnosed with severe depressive episode, irrespective of its curative potential
      on the affective sphere. It may exert even stronger direct effect (assessed with
      DSST) on cognitive functions than duloxetine. With its supplementary capacity of
      acting directly on several subtypes of serotonin receptors, vortioxetine is
      certainly more than just a SSRI. It has been proved that it is as effective as
      venlafaxine and more efficient than agomelatine in MDD treatment, additionally
      exerting procognitive effects. In addition, vortioxetine may be beneficial in
      overcoming sexual dysfunction in patients, who have been suffering from such
      condition as a result of treatment with other antidepressant agents. The drug is
      generally well tolerated with the most prevalent side effects being mild to
      moderate nausea along with (mostly transient) headaches. Vortioxetine may
      significantly improve the quality of life in patients suffering from depression.

PMID- 29634097
TI  - TRACE METAL CONTENT (Cu, Zn, Mn AND Fe) IN URTICA DIOICA L. AND PLANTAGO MAJOR L.
AB  - The aim of the study was to compare the contents of Cu, Zn, Mn and Fe in the
      washed and unwashed leaves and roots of two plant species: Urica dioica L. and
      Plantago major L., used in herbal medicine. These two herb species occur in the
      same environmental habitats, yet their morphological structure is different. The
      soil and plant samples for analyses were collected from an uncontaminated area in
      Eastern Poland. In each habitat location, the samples were taken from sandy soils
      with slightly acidic and neutral pH values. The obtained results showed that U.
      dioica and P. major accumulated similar amounts of trace metals, such as: Cu, Zn
      and Fe, in leaves, despite the differences in the morphological structure of
      their overground parts. The content of Mn in leaves U. dioica was about twice as
      much as in P. major. Also, no differences in the metal content were observed
      between washed and unwashed leaves of both species. However, in the same habitat
      conditions, a significantly higher content of Cu, Zn and Mn was found in the
      roots of P. major than U. dioica. The content of Fe in the roots was similar in
      both species. P. major and U. dioica may be a valuable source of microelements,
      if they are obtained from unpolluted habitats.

PMID- 29634098
TI  - STUDIES ON STABILITY OF 2,3-DIPHENYLCYCLOPROPENONE IN CONTACT WITH WATER AND
      AQUEOUS NaCI SOLUTIONS. CONCLUSIONS FOR PURPOSE OF TOPICAL THERAPY OF PATIENTS
      WITH ALOPECIA AREATA.
AB  - Diphenylcyclopropenone (DCP) is a topically administered agent used for more than
      three decades for treatment of alopecia areata (AA). Moreover, numerous recent
      studies show it's efficiency in treatment of cutaneous metastatic melanoma.
      Despite being a potentially useful drug still very little is known about the
      pharmacokinetics of DCP. The authors investigated the stability of DCP solutions
      in propylene glycol with the addi- tion of 0.9% aquous solution of natrium
      chloride (0.9% NaCI) or with water. DCP was prepared in two concentrations: 0.1%
      and 3%. It's stability was then measured with different proportions of 0.9% NaCI
      or water added and in different temperatures. Contrary to common opinion that DCP
      solutions are extremely unstable, authors have found them to be relatively
      stable. DCP solutions with the addition of equal quantity of 0.9% NaCl decomposed
      slowly at the temperature of 37C but after 70 h all solutions still contained
      more than 80% of initial DCP. Solutions of DCP with the addition of 1% of water
      at the temperature of 4'C are in the present study stable, containing more than
      98% of initial DCP after 20 days. Authors discuss the results in spite of
      possible metabolism of DCP on the surface of human skin during topical
      immunotherapy.

PMID- 29634099
TI  - OPTIMIZATION AND VALIDATION OF HPLC METHOD FOR TETRAMETHRIN DETERMINATION IN
      HUMAN SHAMPOO FORMULATION.
AB  - High-performance liquid chromatography (HPLC) method with diode array detection
      (DAD) were optimized and validated for separation and determination of
      tetramethrin in an antiparasitic human shampoo. In order to optimize separation
      conditions, two different columns, different column oven temperatures, as well as
      mobile phase composition and ratio, were tested. Best separation was achieved on
      the Supelcosil TM LC-18- DB column (4.6 x 250 mm), particle size 5 jim, with
      mobile phase methanol : water (78 : 22, v/v) at a flow rate of 0.8 mL/min and at
      temperature of 300C. The detection wavelength of the detector was set at 220 nm.
      Under the optimum chromatographic conditions, standard calibration curve was
      measured with good linearity [r2 = 0.9997]. Accuracy of the method defined as a
      mean recovery of tetramethrin from shampoo matrix was 100.09%. The advantages of
      this method are that it can easily be used for the routine analysis of drug
      tetramethrin in pharmaceutical formulas and in all pharmaceutical researches
      involving tetramethrin.

PMID- 29634100
TI  - IDENTIFICATION AND DETERMINATION OF RUPATADINE AND FEXOFENADINE BY DENSITOMETRIC
      METHOD.
AB  - Simple, precise and accurate densitometric methods were developed for the
      determination of two antihistamine drugs. rupatadine and fexofenadine. Silica gel
      60 F254 HPTLC plates were used as stationary phase, while mixtures of
      acetonitrile - water - 25% ammonia (90 : 10 : 1, v/v/v) and acetonitrile -
      methanol -acetate buffer at pH 5.5 (3 : 2 : 5, v/v/v) were used as mobile phases
      for rupatadine and fexofenadine, respectively. The detection of rupatadine and
      fexofenadine was conducted out at 256 and 210 nm, respectively. The limit of
      detection and the limit of quantification for rupatadine were found to be 0.3 and
      0.1 MUg/spot, respectively, and for fexofenadine, 5 and 2 MUg/spot, respectively.

PMID- 29634101
TI  - RP-HPLC ANALYSIS OF ACIDIC AND BASIC DRUGS IN SYSTEMS WITH DIETHYLAMINE AS
      ELUENTS ADDITIVE.
AB  - The chromatographic behavior of some basic and acidic drugs was studied on Cl 8,
      Phenyl-Hexyl and Polar RP columns with methanol or acetonitrile as organic
      modifiers of aqueous mobile phases containing addition of diethylamine.
      Diethylamine plays a double function of silanol blocker reagent in analysis of
      basic drugs and ion-pair reagent in analysis of acidic drugs. Most symmetrical
      peaks and highest system efficiency were obtained on Phenyl-Hexyl and Polar RP
      columns in tested mobile phase systems compared to results obtained on C18
      column. A new rapid, simple, specific and accurate reverse phase liquid
      chromatographic method was developed for the simultaneous determination of
      atorvastatin - antihyperlipidemic drug and amlodipine - calcium channel blocker
      in one pharmaceutical formulation. Atorvastatin is an acidic compounds while
      amlodipine is a basic substance. The chromatographic separation was carried out
      on Phenyl-Hexyl column by gradient elution mode with acetonitrile as organic
      modifier, acetate buffer at pH 3.5 and Q.025 M/L diethylamine. The proposed
      method was validated for specificity, precision, accuracy, linearity, and
      robustness. The linearity range of atorvastatin and amlodipine for 5 - 100 MUg/mL
      was obtained with limits of-detection (LOD) 3.2750 gg/mL and 3.2102 MUg/mL,
      respectively. The proposed method made use of DAD as a tool for peak identity and
      purity confirmation.

PMID- 29634102
TI  - ENVIRONMENTALLY FRIENDLY LC/MS DETERMINATION OF EPLERENONE IN HUMAN PLASMA.
AB  - Eplerenone (EPL), a selective aldosterone receptor antagonist, is indicated in
      the treatment of chronic heart failure and hypertension. It is hard to find a
      green assay among a few published methods for its determination in human plasma
      or serum. Following a liquid-liquid extraction with methyl t-butyl ether,
      eplerenone and isotope labelled eplerenone - used as an internal standard - were
      separated from the endogenous compounds on an Atlantis dCl8 column (150 x 3 mm,
      3.0 [im). An isocratic elution with the mobile phase consisting of methanol and
      ammonium acetate (3 : 2, v/v) was used. A single quadrupole mass spectrometer was
      operated in positive electrospray ionization using the selected ion monitoring
      mode. The method is more environmentally-friendly than the previously reported
      assays. Acetonitrile in the mobile phase was replaced with methanol which is a
      removable solvent. Plasma sample volume was reduced to 250 pL which significantly
      decreased waste volume. Chlorinated solvents used previously for liquid-liquid
      extraction were eliminated and the safety of the laboratory staff was increased
      by eliminating diethyl ether. The method is characterized by a short analysis
      time, simple sample preparation and reduction of waste volume, which are
      important advantages when analyzing large numbers of samples. The method was
      validated according to international regulatory guidelines and may be applied to
      human pharmacokinetic studies following a single 25 or 50 mg oral dose.

PMID- 29634103
TI  - HPLC-UV ASSAY OF IMATINIB IN HUMAN PLASMA OPTIMIZED FOR BIOEQUIVALENCE STUDIES.
AB  - lmatimb is an anticancer drug approved for the treatment of a number of cancers,
      mostly used in chronic myeloid leukemia. Numerous bioanalytical methods using
      high performance liquid chromatography coupled to ultraviolet detection point at
      the importance and necessity of the therapeutic drug monitoring of imatinib.
      Unfortunately, these methods are not optimized for single dose pharmacokinetic
      studies such as bioe- quivalence. In this study, attention was turned mostly to
      the analysis time, linearity range and interferences by endogenous components of
      the matrix and exogenous substances - especially metabolites. The method enables
      the quantification of imatinib in the presence of the main metabolite (N
      desmethyl imatinib). Its potential back- conversion was examined during storage
      for 4 h at ambient temperature as well as for 239 days at -200C. The sample
      preparation based on the liquid-liquid extraction was combined with a short
      analysis time of 7 min. Therefore, the method was suitable for analyzing large
      numbers of samples in a short time. The linearity range of 40-4000 ng/mL was
      optimized for human pharmacokinetic studies after a single 400 mg oral dose of
      ima- tinib. Successful application in a bioequivalence study confirmed the
      reliability of the method.

PMID- 29634104
TI  - ANTIOXIDANT ACTIVITY OF XANTHONE DERIVATIVES.
AB  - Certain xanthone derivatives, such as these present in mangosteen fruits, show
      strong antioxidant activity. On the other hand, evidences accumulated that
      oxidative stress is involved in epileptogenesis. Therefore, the aim of the
      present study was to estimate total antioxidant capacity (expressed as a ferric
      reducing antioxidant power - FRAP) and evaluate ability to scavenge free radicals
      (DPPH methods) by xanthone derivatives showing antiepileptic activity. Selected 2
      (aminomethyl)-9H-xanthen-9-one derivatives shared structural features, such as
      chlorine substituent in xanthone ring and different chiral (or not) alkanol
      groups at the nitrogen atom. The results of antioxidant activities among
      racemates revealed the highest activity for compound (RIS)-3 (31.7% in diphenyl-2
      picrylhydrazyl (DPPH) radical scavenging and (0.184 +/- 0.003 mM Fe2+/L) in FRAP
      assay. Among tested pair of enantiomers we observed that (R)-1 and (R)-2 showed
      higher reduction capacity ((R)-1: 0.096 +/- 0.007 mM F2+/L; (R)-2: 0.048 +/-
      0.005 mM Fe2+/L, respectively) and stronger DPPH scavenging activity ((R)-1: 31
      +/- 3.0%; (R)-2: 29 +/- 2.5%, respectively) comparing to their (S)-enantiomers
      and racemates.

PMID- 29634105
TI  - IN VITRO ANTIFUNGAL ACTIVITY OF 2,4-DIHYDROXY-N-(3-THIOXO-3H- 1,2,4-DITHIAZOL-5
      YL)BENZENECARBOTHIOAMIDE.
AB  - An increase in infections due to non albicans species of Candida has been
      observed in the recent years. The aims of this study were to determine the
      antifungal activity of 2,4-dihydroxy-N-(3-thioxo-3H-l1,2,4-dithiazol-5
      yl)benzenecarbothioamide (DNTDB) against C. albicans, non-C. albicans,
      dermatophytes, and molds and to evaluate the enzymatic activity of C. albicans
      strains. We used reference strans C. albicans 10231 ATCC, 200 C. albicans
      strains, 100 non-C. albicans, 19 dermatophyte strains, and 21 mold strains
      isolated from different ontocenoses from patients. DNTDB revealed a mean minimum
      inhibitory concentration (MIC) of 12.5 pg/mL against the reference C. albicans
      10231 ATCC strain on Sabouraud agar (SA) and of 6.5 pg/mL on Roswell Park
      Memorial Institute (RPMI) medium. The mean MIC for C. albicans isolates was of
      22.01 +/- 7.5 MUg/mL on SA, 17.8 +/- 7.4 MUg/mL on yeast nitrogen base (YNB), and
      16.9 +/- 7.9 MUg/mL on RPMI medium. The mean MIC for non-C. albicans isolates was
      of 22.4 +/- 12.4 MUg/mL on SA, 18.2 +/- 8.6 MUg/mL on YNB and 15.2 +/- 9.03 sg/mL
      on RPMI. Against Trichophyton mentagrophytes v. granulosum, the mean MIC was 10.9
      +/- 2.04 MUg/mL after 5 days of incubation and 21.9 +/- 3.8 MUg/mL after 15 days,
      while Trichophyton mentagrophytes . inteiligitale showed a mean MIC of 13.3 +/-
      5.5 MUg/mL and of 20.3 +/- 6.1. MUg/mL after the same incubation periods,
      respectively. DNTDB manifested a MIC over the test range of 25-100 MUg/mL for
      molds after 5 days of incubation and inhibited the enzymatic activity of Candida
      strains. It seems, the new DNTDB demonstrates potential antifungal activity
      against yeast-like fungus strains, dermatophytes, and molds in vitro.

PMID- 29634106
TI  - EFFECT OF COLLA CORNUS CERVI COMBINED WITH LV-MEDIATED BMP7 TRANSFECTED BMSCs ON
      ANFH IN RATS.
AB  - In the present study, we investigated the combined effect of Colla Comus Cervi
      (CCC) and BMP7-overexpressing bone marrow-derived mesenchymal stem cells (BMSCs)
      on osteogenic induction and the treatment of avascular necrosis of the femoral
      head (ANFH). BMSCs were isolated from rats. BMP7-overexpressing BMSCs were
      generated by lentiviral-mediated gene transduction. Cell proliferation, alkaline
      phosphatase (ALP) activity, osteogenesis related gene expression, osteocalcin
      levels, and calcified nodules were quantified and compared between four groups:
      untreated controls, BMSCs cultured with CCC complex medium, BMP7-overexpressing
      BMSCs, and BMP7-overexpressing BMSCs cultured with CCC complex medium (CCC+BMP7).
      CCC+BMP7 BMSCs showed higher proliferation rate. ALP activity and osteaocalcin
      content were significantly increased in CCC+BMP7 BMSCs. The osteogenesis related
      genes, COLI, and integrin-alpha2, -alpha5, and -beta1, were expressed
      significantly higher in CCC+BMP7 BMSCs. The number of calcified nodules in the
      CCC+BMP7 group was significantly higher than that in other groups. For in vivo
      assays, ANFH was induced in rats, and BMSCs were injected into the femoral head
      of the lower left extremity. In rats with induced ANFH, general observation
      scores of the CCC+BMP7 injected group were significantly higher than the model
      group. X-ray and microscopic observations revealed that ANFH was significantly
      improved and femoral head cells gradually recovered in rats treated with CCC+BMP7
      BMSCs. Our results suggest that CCC+BMP7 significantly promote the proliferation
      and osteogenic differentiation of BMSCs in vitm. CCC+BMP7 BMSCs promote the
      ability of repairing ANFH in rats, providing a new therapeutic paradigm for the
      treatment of ANFH.

PMID- 29634107
TI  - INACTIVATION OF ALDEHYDE DEHYDROGENASE BY NITROGLYCERIN IN THE PRESENCE AND
      ABSENCE OF LIPOIC ACID AND DIHYDROLIPOIC ACID. IMPLICATIONS FOR THE PROBLEM OF
      DIFFERENTIAL EFFECTS OF LIPOIC ACID IN VITRO AND IN VIVO.
AB  - Lipoic acid (LA-(SS), LA) and its reduced form - dihydrolipoic acid DHLA-(SH)2,
      DHLA) are synthesized mainly in the mammalian liver. In this study, we
      investigated in viti the inactivation of yeast aldehyde dehydrogenase (ALDH) by
      nitroglycerin (GTN) in the presence and absence of LA and DHLA. In vivo studies
      were performed to answer the question whether LA administered jointly with GTN
      for 8 days will affect the ALDH activity in the rat liver. The results indicated
      that in vito both LA and DHLA restored and protected ALDH activity against GTN
      induced inactivation, while treatment of rats with LA and GTN in combination did
      not provide any protection against GTN-induced ALDH inhibition. In summary, the
      obtained results seem to confirm earlier reports indicating the differential
      effects of LA in vitio and in vivo.

PMID- 29634108
TI  - ANTI-ADHESIVE AND ANTI-BIOFILM ACTIVITIES IN VITRO OF LINEZOLID, VANCOMYCIN,
      TIGECYCLINE AND DAPTOMYCIN AGAINST STAPHYLOCOCCUS HAEMOLYTICUS.
AB  - Biofilm may be formed on wide variety of surfaces, including indwelling medical
      devices, leading to several infectious diseases, e.g., bacteremia and sepsis. The
      most,important pathogens related with infections associated with medical devices
      are coagulase-negative staphylococci, including Staphylococcus haeinolyticus -
      bacterial species which express quite often the multidrug resistance. The four
      clinical multiresistant and methicillin-resistant S. haenzolyticus were included
      in the present study. The evaluation of drug susceptibility was performed by
      using disc-diffusion method and broth microdilution method according to European
      Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. The
      biofilm formation on the Nelaton catheter and the effect of linezolid,
      vancomycin, tigecycline and daptomycin on the biofilm formation and disruption of
      mature structure was based on the method with TTC (2,3,5-triphenyltetrazolium
      chloride). The adhesion process of S. haenzolyticus to the Nelaton catheter was
      inhibited by antibiotics, as follows: line-zolid at concentration 0.25-0.5 x MIC,
      vancomycin - concentration 0.5 x MIC, tigecycline - concentration 0.25-4 x MIC
      and daptomycin - concentration 0.06-1 x MIC, depending on the isolate. Linezolid
      inhibited the biofilm formation at concentration between 0.5-1 x MIC, vancomycin 
      1-2 x MIC, tigecycline - 0.5-4 x MIC and daptomycin - 0.06-2 x MIC. The
      concentration of linezolid eradicating the mature biofilm was found to be 1-2 x
      MIC, vancomycin - 2-8 x MIC, tigecycline - 2-4 x MIC and daptomycin - 0.06-2 x
      MIC. The most active antibiotic against S. haentolyticus biofilm formation and
      disruption of mature structure seems to be daptomycin.

PMID- 29634109
TI  - NEW SPIROHYDANTOIN DERIVATIVES - SYNTHESIS, PHARMACOLOGICAL EVALUATION, AND
      MOLECULAR MODELING STUDY.
AB  - A series of new arylpiperazinylpropyl derivatives of 8/6-phenyl-1,3
      diazaspiro[4.5]decan-2,4-dione and spiro[imidazolidine-4,1'-indene/naphthalene]
      2,5-dione was synthesized and their affinity was evaluated toward serotonin 5
      HTIA, 5-HT2A, 5-HT7 receptors, dopaminergic D2, D3 receptors, adrenergic ox,
      receptors, and serotonin transporter (SERT). The highest affinity for serotonin 5
      HT1A/2A/7 receptors was found for compounds containing a tetralin or indane
      moiety in the imide part. Among these, two compounds (19, 20) were selected for
      further pharmacological in vivo studies. A binding mode of representative
      molecule 19, which behaved as a 5-HT1A agonist and weak 5-HT7 antagonist in the
      site of 5-HT 1A/7, was also analyzed in computational stud- ies. Moreover, two
      highly selective (9 and HI) 5-HT2A receptor antagonists were obtained.

PMID- 29634110
TI  - PRODUCTION OF ANTIMICROBIAL PEPTIDES BY EPICOCCUM SP. NFW1: AN ENDOPHYTE OF TAXUS
      FAUNA.
AB  - An endophytic fungus NFWI, possessing antimicrobial activity against bacterial
      and fungal pathogens, was isolated from indigenous Taxus fauna. Phylogenetic
      analysis coupled with cultural and morphological characteristics revealed that
      endophyte NFWI closely resembles Epicoccum sp. It showed optimum growth and
      antimicrobial activity in mineral salt medium TM, incubation temperature 250C,
      incubation time 15 days and pH 6.5. Antimicrobial peptides were precipitated with
      80% ammonium sulfate and expressed significant inhibitory effect against
      Staphylococcus aureus (ATCC6538) and Candida albicans (CI.I 4043). It also
      inhibited growth of Streptomyces 85E in hyphae formation inhibition assay showing
      potential as protein kinase inhibitor. Gel filtration chromatography on Sephadex
      G-75, followed by sodium dodecyl sulfate polyacrylamide gel electrophoresis
      resolved the crude precipitate into three fractions of molecular mass 32 kDa, 44
      kDa and 70 kDa. The study concludes that endophytic fungi associated with
      indigenous Taxus species possess promising antimicrobial activities and should be
      exploited as source of novel antimicrobial agents.

PMID- 29634111
TI  - ANTIMICROBIAL AND ANTIBIOFILM EFFECTS OF EXTRACTS FROM TRAPA NATANS L.,
      EVALUATION OF TOTAL PHENOLIC AND FLAVONOID CONTENTS AND GC-MS ANALYSIS.
AB  - Research conducted in this study shows the applied in vitro antimicrobial and
      antibiofilm activity of the four extracts isolated from Trapa natans L. leaves.
      In this study, different methods were used (microdilution, tissue culture plate,
      different colorimetric methods, GC-FID and GC-MS analysis). While the water
      extract didn't show antibacterial activity, the acetone extract showed the
      strongest one. The same activity in the case of Pseudomonas aeruginosa (MIC was
      313 MUg/mL) was better than the activity of controls and it matched with
      antibiofilm activity. The effect of extracts was better on G+ bacteria (MICs were
      <78-625 MUg/mL). For ethanol and ethyl acetate extracts all BIC values were
      better than MICs. Extracts showed a significant effect on Aspergillus restrictus
      (MICs were < 78/156 MUg/mL). The GC and GC-MS analysis of the ethyl acetate
      extract revealed the identification of 22 compounds with (all E)-squalene
      (20.2%), n-alkanes and norlignan hinokiresinol among the most abundant ones. This
      is the first time that T. natans was studied using these methods.

PMID- 29634112
TI  - ANTIDIABETIC AND ANTIDYSLIPIDEMIC EFFECTS OF HELIOTROPIUM STRIGOSUM IN RAT MODELS
      OF TYPE I AND TYPE II DIABETES.
AB  - Heliotropiumz stnigosum Wilid. (Boraginaceae) is used traditionally as a
      laxative, diuretic, and as a treatment for snake bites and stings of nettles.
      Recent investigations have shown anti-inflammatory and antioxidant activity of H.
      sorigosum. However, antihyperglycemic and antidyslipidemic activity of H.
      strigosum has not been investigated to date and we aimed to explore these
      activities of the crude aqueous methanolic extract of thEaerial parts of H.
      strigosum (Hs.Cr). Hs.Cr was administered orally at doses of 100, 300, and 500
      mg/kg in alloxan-induced diabetic rats (type I diabetes) and fructose-fed rats
      (type II diabetes). The fasting blood glucose (FBG) concentration was assessed by
      glucometer, while semum total cholesterol, triglycerides and HDL were estimated
      by using standard kits. The FBG concentration significantly (p < 0.05) decreased
      in dose-dependent pattern in both alloxan-induced diabetic and fructose-fed rats
      on Hs.Cr administration. The percentage glucose reductions in alloxanized rats
      with glibenclamide, Hs.Cr 100, 300, and 500 mg/kg were obeserved to be 67, 36, 56
      and 62%, respectively. In fructose-fed rats, the percentage glucose redutions
      associated with metformin, Hs.Cr 100, 300, and 500 mg/kg were 23, 5, 11 and 12%,
      respectively. The extract also corrected the dyslipidemia associated with
      fructose and alloxan-induced diabetes by significantly (p < 0.00 1) decreasing
      the concentration of serum total cholesterol, triglycerides and LDL and by
      increasing HDL concentration. Our data demonstrate that the H. stigosum has
      antidiabetic and antidyslipidemic effects, thus encouraging further studies.

PMID- 29634113
TI  - CYTOTOXIC EFFECTS OF THE RED SEA SOFT CORAL SARCOPHYTON TROCHELIOPHORUM.
AB  - The present study describes the in vitro cytotoxic effects of soft coral
      (Sarcophyton tiocheliophorum). Soft corals of genus Sarcophyton were reported to
      contain compounds that are active against brine shrimp and promote paclitaxel
      cytotoxicity in the human colon cancer Caco-2 cell line. The n-hexane extract of
      the soft coral Sarcophyton tiocheliophorum induced significant dose-dependent
      toxicity (LC50 96.7 ppm) compared with ethyl acetate (LC50. 120 ppm). We reported
      the most active cytotoxic level to be correspondence to LC50 values of 20.2, 59.2
      ppm and 18.9 and 26 ppm. Accordingly, bio-assay guided fractionation was
      conducted to identi- fy the bioactive compounds. Arachidonic acid,
      eicosapentaenoic acid and docosahexaenoic acid were characterized based on GC-MS
      analyses. Our results demonstrate the value of marine products as a natural
      source of medicinally interesting cytotoxic compounds.

PMID- 29634114
TI  - CHEMICAL CONSTITUENTS AND IN VITRO ANTIOXIDANT ACTIVITY OF CRUDE EXTRACTS AND
      COMPOUNDS FROM LEAVES AND STEM BARK OF FICUS BURTT-DAVYI.
AB  - Ficus buit-davyi, (Moraceae), is an endemic species of South Africa. In this
      study, a phytochemical analysis of the leaves and stem bark of F. burt-davyi
      resulted in the isolation of five triterpenes (lupeol, lupeol acetate, beta
      sitosterol, stigmasterol and campesterol), one carotenoid (lutein), a pheophytin
      (phytyl-7-ethyl-25- (methoxycarbonyl)-3,8,13,17-tetramethyl-26-oxo- 12-vinyl
      17,18-dihydro-2,20-ethanoporphyrin- 1 8-propanoate or pheophytin a) and one
      flavonoid (+)-catechin). The in viti antioxidant study of the methanol extracts
      of leaves and stem bark, (+)-catechin and pheophytin a using the 1,1-diphenyl-1
      picrylhydrazyl (DPPH) free radical scavenging assay, ferric reducing antioxidant
      power (FRAP) assay and hydrogen peroxide (H202) assay showed significantly higher
      (p < 0.05) antioxidant activity for the methanol extract of the stem bark than
      the leaves, with IC55 values (in MUg/mL) of 58.28 ? 5.05 for DPPH, 46.09 +/- 0.06
      for FRAP and 151.03 +/- 1.60 pg/mL for H202,. The results suggest that the plant
      can be used as a therapeutic agent in alternative medicine for oxidative stress
      related degenerative diseases.

PMID- 29634115
TI  - EVALUATION OF ANTI-INFLAMMATORY, ANALGESIC AND ANTIPYRETIC ACTIVITIES OF AQUEOUS
      AND ETHANOLIC EXTRACTS OF SEEDS OF BUCHANANIA LANZAN SPRENG. IN ANIMAL MODELS.
AB  - The present study was designed to evaluate the anti-inflammatory, analgesic and
      antipyretic activities of the aqueous and ethanolic extracts of seeds of
      Buchanania lanzan Spreng. Albino mice were used as experimental animals to
      evaluate these activities. The study was performed in three phases; Phase-I for
      evaluation of anti-inflammatory activity, Phase-II for antipyretic and Phase-HI
      for analgesic activities were evaluated. Carrageenan induced paw edema, brewer
      yeast induced pyrexia and acetic acid induced writhing methods were used to
      evaluate anti-inflammatory, antipyretic and analgesic activities, respectively.
      Tests were performed by dividing the animals in five groups. First group was
      negative control, second group was positive control, third, fourth and fifth
      groups were treated with 125, 250 and 500 mg/kg of extracts. respectively. The
      data were statistically analyzed using ANOVA where p < 0.05 were considered
      significant. The results suggested that seeds of Buchanania lanzan Spreng.
      possess anti-inflammatory, analgesic and antipyretic activity.

PMID- 29634116
TI  - COMMERCIAL EXTRACT FROM ARONIA AS A MODULATOR OF ADHESIVE PROPERTIES OF
      FIBRINOGEN TREATED WITH HOMOCYSTEINE AND ITS THIOLACTONE IN VITRO.
AB  - Research has confirmed the positive effect of berries of Aivnia melanocarpa on
      the cardiovascular system. The protective effects of polyphenol-rich extract from
      berries of A. melanocarpa against changes in biological properties of fibrinogen
      were studied. In in vino model of hyperhomocysteinemia the capability of
      fibrinogen to interact with human blood platelets was measured by platelet
      adhesion in the presence of extract fromA. nelanocapa. We induced
      hyperhomocystenemia using a reduced form of homocysteine (Hey, at a final
      concentration of 0.01. 0.1 and 1 MUM) and the most reactive form of Hey - its
      cyclic thioester, homocysteine thiolactone (HTL, at a final concentration of 0.1,
      0.5 and I MUM). It was observed that Hey or HTL-treated fibrinogen, in comparison
      with untreated molecule, had a distinct capability to mediate blood platelet
      adhesion. The experiments also indicate that polyphenol-rich extract from black
      chokeberries (at final concentrations of 2.5-10 pM/mL) reduced the toxic action
      of Hey and HTL on the adhesive properties of fibrinogen. The possible protection
      exerted by black chokeberry extract, through restoring the platelet adhesion of
      Hey or HTL treated fibrinogen, may be important for vascular diseases.

PMID- 29634117
TI  - WOUND HEALING ACTIVITY OF EXTRACT FROM THYMUS DAENENSIS IN BURN WOUND MODEL: AN
      EXPERIMENTAL ANIMAL STUDY.
AB  - Bum wound is one of the most common complications and remains a major public
      health issue affecting all ages groups in both developed and developing
      countries. This study was aimed to evaluate the extract from Thymus daenensis and
      silver sulfadiazine on healing bum wounds in mice. In this experimental study,
      the ethanol extract from the aerial parts of T. daenensis (Lamiaceae) was used.
      Second-degree bum wounds were induced in three groups of eight Balb/C mice each.
      Group-I: the animals were treated with simple cream (control), Group-II: the
      animals were treated with simple cream containing the herb extract, and Group
      III: the animals received the standard drug (silver sulfadiazine). The
      experimental groups were evaluated based on wound area, epithelialization time
      and histopathological characteristics. There were significant differences in
      surface area and the period of bum wound healing between the groups, particularly
      among Group-II when the animals received the extract of T. daenensis in
      comparison with control. At the 18" day, there was no significant improvement in
      healing percentage of the herb treated (94.6%) in comparison to the animals
      receiving the standard drug (95.8%). The best results of histopathological
      investigation were obtained with the extract of T. daenensis, when compared to
      the other group as well as to the control and standard drug. The herbal cream
      experimentally and histopathologically revealed a bum wound healing activity
      probably due to the antioxidant and anti-inflammatory activity of its
      phytochemical contents, especially phenolic compounds. Therefore, T. daenensis
      accelerated wound healing in mice and thus supports its traditional use.

PMID- 29634118
TI  - DETERMINATION OF ANTIMICROBIAL ACTIVITY OF CHLORHEXIDINE GEL.
AB  - Many researchers have advocated in recent times that antiseptic use in healing
      wounds should be discouraged. Antiseptics have been found to retard healing of
      wounds. Poloxamer 407 shows thermoreversible properties, which are of the utmost
      interest in optimizing drug formulation (fluid state at room temperature
      facilitating administration and gel state above sol-gel transition temperature,
      at body temperature, promoting prolonged release of pharmacological agents).
      Chlorhexidine, a commonly used antiseptic, is known to be less toxic on
      granulation cells. Acting as an antiseptic, it is an effective bactericidal agent
      against the most categories of microbes, including bacteria, yeast, and viruses.
      Objective of this study was to evaluate antimicrobial activ- ity of chlorhexidine
      containing poloxamer gel to Gram-positive and Gram-negative bacteria in vitro.
      Chlorhexidine gels and chlorhexidine aqueous solutions have different
      antibacterial activity to S. amis, E.faecalis, E. coli and P. aemginosa strains
      in vitro. It depends on concentration and dosage form of antiseptic. Study
      results confirmed that antimicrobial activity of gel depends on active ingredient
      concentration in antiseptic. The best inhibition effect for both of reference and
      wild-type bacteria was obtained for 1% chlorhexidine gel. Summarizing the results
      and assessing the characteristics of the gel ingredients, it can be suggested
      using chlorhexidine gels in veterinary medicine.

PMID- 29634119
TI  - DEVELOPMENT OF SOLID LIPID NANOCARRIERS FOR ORAL DELIVERY OF CANDESERTAN
      CILEXETIL.
AB  - Candesertan cilexetil is a Biopharmaceutics Classification System (BCS) Class II
      drug possessing high permeability but low aqueous solubility; hence its oral
      bioavailability is limited in terms of the solubility rate. The aim of this
      research was to develop solid lipid nanopa rticle (SLN) drug delivery systems of
      candesertan cilexetil to enhance its aqueous solubility, thereby improving the
      oral bioavailability of the drug. SLN formulations were produced using a combined
      technique of high shear homogenization and ultrasonication method. Drug/lipid and
      surfactant/co-surfactant ratios of the candesertan cilexetil loaded SLNs were
      investigated based on various final characteristics of the nanocarriers; namely,
      encapsulation efficiency, average particle diameter, size distribution, surface
      charge, thermal behavior, and in vitro drug release profiles. Lipid based
      nanocarriers of candesertan cilexetil displayed spherical particles having a
      nanometer size. High encapsulation efficiencies were obtained due to the high
      lipid solubility of the drug. DSC analysis demonstrated the transformation of the
      crystalline structure of candesertan cilexetil to amorphous form into the SLN
      formulations and there was no interaction between the drug and the excipients.
      Consequently, the oral delivery of candesertan cilexetil with the design of
      Compritol(r) 888 ATO based lipid nanocarriers may lead to an increase in
      bioavailability of the drug and thus, more effective therapy may be obtained.

PMID- 29634120
TI  - PREPARATION, IN VITRO AND IN VIVO CHARACTERIZATION OF HYDROPHOBIC PATCHES OF A
      HIGHLY WATER SOLUBLE DRUG FOR PROLONGED PLASMA HALF LIFE: EFFECT OF PERMEATION
      ENHANCERS.
AB  - Aim of present study was to develop metoprolol matrix patches using different
      enhancers. Combination of two hydrophobic polymers, ethyl cellulose and eudragit
      RL 100 (8 : 2) were used for preparation of unilaminated matrix patch. 10% w/w of
      isopropyl myristate (IPM), dimethyl sulfoxide (DMSO), span (20 (S20), Tween 20
      (T20) and eucalyptus oil as enhancers and 40% of dibutyl phthalate as plasticizer
      were used. Prepared patches were evaluated for physical appearance, weight
      uniformity and thickness. FTIR studies were performed to assess compatibility
      among ingredients and developed formulation. Dissolution and permeation studies
      were performed to compare effects of enhancers. Surface morphology after release
      was examined by scanning electron microscopy. Selected formulation was subjected
      to in vivo studies by randomized crossover design in rabbits (n = 6) for
      pharmacokinetic comparison with oral solution administration. Physical evaluation
      revealed that translucent, flexible, non brittle patches of uniform weight and
      thickness were prepared. Release from patches followed Higuchi model. Mechanism
      of release was Fickian. Formulation containing IPM showed that release was by
      anomalous transport. Highest permeation flux was observed for formulation
      containing IPM with 2-fold enhancement in permeation. Permeation flux for patches
      was in order of formulation with no enhancer > IPM > T20 > S20 > DMSO =
      eucalyptus oil. Plasma concentration from in vivo studies exhibited sustained
      plasma levels of metoprolol after transdermal patch application in comparison to
      oral solution administration. Pharmacokinetic analysis of in vivo data elucidated
      that half life was increased 8 times when compared to oral administration, due to
      controlled release of drug for longer period of time. These findings suggested
      that hydrophobic transdermal patches of highly water soluble drug metoprolol were
      successfully prepared with 10% of IPM for sustained systemic delivery for
      prolonged half life.

PMID- 29634121
TI  - THE INVESTIGATION OF EFFECT OF FLURBIPROFEN AXETIL ON THE TISSUE GROWTH AND THE
      CONTENT OF PGE2 IN CERVICAL CANCER.
AB  - The aim of this study was to investigate whether flurbiprofen axetil can inhibit
      the tissue growth and the content of PGE2 in cervical cancer or not. Fifty female
      BALB/c nude mice were randomly divided into control group (C), tumor + saline
      group (T), tumor + flurbiprofen axetil 10 mg/kg (Cfl0) group, tumor +
      flurbiprofen axetil 25 mg/kg (Cf25) group, tumor + flurbiprofen axetil tumor 50
      mg/kg (Cf50), so that each group had 10 animals. Then, the animal model of human
      cervical carcinoma was established, and the relative tumor volume (RTV), relative
      tumor proliferation rate (T/C) and tumor inhibition rate were measured. The
      content of PGE2 in tumor tissue was determined by using enzyme-linked
      immunosorbent assay. There was no tumor formation in group C, and the time of
      tumor growth in other groups was non-statistically different. The RVT in Cf50
      group was lower than in other groups. It was evident from the curve of tumor
      growth that the tumor weight in T group was evidently higher than that of
      administration groups (p < 0.01). The tumor inhibition rates of Cf10, Cf25 and
      Cf50 groups were 16.8, 19.6 and 36%, respectively, and the relative tumor
      proliferation rate were 85, 91 and 72%, respectively. The PGE, level of Cf50 was
      statistically (p < 0.01) lower than that of Cfl0 and Cf25 groups. Flurbiprofen
      axetil can inhibit the growth of cervical cancer transplanted tumor in nude mice
      and this inhibitory effect was maximal in Cf50 group. Flurbiprofen axetil can
      inhibit the production of PGE2 in tumor tissue of cervical carcinoma in nude
      mice.

PMID- 29634122
TI  - PATIENTS' KNOWLEDGE OF MEDICAL PATCHES IN HUNGARY.
AB  - Transdermal therapy with medical patches is a simple possibility in home
      medication. As the correct use of patches has a decisive impact from the point of
      its modulator effect.A questionnaire survey was developed to explore level of
      patients' knowledge of the correct use of transdermal patches. A survey was
      administered in thirteen Hungarian community pharmacies from October of 2012 to
      May of 2015. Most of the participants, men and women over 18 years of age (n =
      233), used major analgesic patches (fentanyl); the remainder were given
      nitroglycerin, NSAID analgesics patches during the survey. For the hypothesis
      testing it was assumed that men were more likely to use a razor for skin
      depilation before patch application than women as their denser pelage hinders
      patch adhesion. The hypothesis testing showed no significant gender difference in
      razor use (X2 = 0.201; p = 0.654). Pharmacists should direct patients to avoid
      using soap for skin cleansing before patch application because only 22 percent of
      the participants always avoided its use. Since only 9 tests were flawless from
      233 completed questionnaires. Many patients do not understand how to correctly
      apply a transdermal dosage patch. Pharmacists should teach their correct
      application based on results.

PMID- 29634123
TI  - SOCIO-ECONOMIC CONSTRAINS FACED BY TB PATIENTS THAT LEAD TO NON-COMPLIANCE - A
      CROSS SECTIONAL STUDY IN SOUTHERN PUNJAB, PAKISTAN.
AB  - Tuberculosis (TB) is an infectious disease that is communicable from one person
      to another. Pakistan stands forefront among few unfortunate countries that still
      have heavy burden of TB infection. Being a developing country, TB patients in
      Pakistan have to face different socio-economic constraints that upset life of the
      patients as well as their families. A cross sectional survey was conducted in
      three selected districts, Lodharan, Bahawalpur and Bahawalnagar during February
      2011 to June 2011. From three hundred selected patients 210 were enrolled in
      study after receiving written consents. Data were collected though structured
      questionnaire and verbal interviews and statistically analyzed by using the
      univariate analysis. The survey results showed that the low educational status (p
      < 0.0012, CI 95%), unawareness of disease (88.7%), crowded population (p =0.0000,
      CI, 95%), poverty, high treatment cost and distant access to public health
      facilities were directly related to prevalence of TB. Different disease related
      constraints including poor attitude of family members, colleagues, society and
      even health care professionals (p = 0.0000, CI 95%) were also found to be major
      social factors leading to non-compliance and denial of TB treatment. Socio
      economic constraints such as low literacy rate, unemployment, unawareness of
      disease, high treatment cost, poor attitude of family, society and health care
      professionals were directly related to noncompliance and should be given high
      priority consideration for achieving better TB management and mitigation.

PMID- 29634124
TI  - EVALUATION OF SPERMICIDAL PROPERTY OF HIPPOPHAE RHAMNOIDES L. BERRIES.

PMID- 29634125
TI  - [The 95th year anniversary of the journal Urologiia. What has changed over the
      past five years?]

PMID- 29634126
TI  - [Resolution of the XIII Meeting and XVII Congress of the RSU].

PMID- 29634127
TI  - [Non-biological 3D printed simulator for training in percutaneous nephro-
      lithotripsy].
AB  - AIM: To develop a non-biological 3D printed simulator for training and
      preoperative planning in percutaneous nephrolithotripsy (PCNL), which allows
      doctors to master and perform all stages of the operation under ultrasound and
      fluoroscopy guidance. MATERIALS AND METHODS: The 3D model was constructed using
      multislice spiral computed tomography (MSCT) images of a patient with staghorn
      urolithiasis. The MSCT data were processed and used to print the model. The
      simulator consisted of two parts: a non-biological 3D printed soft model of a
      kidney with reproduced intra-renal vascular and collecting systems and a printed
      3D model of a human body. Using this 3D printed simulator, PCNL was performed in
      the interventional radiology operating room under ultrasound and fluoroscopy
      guidance. RESULTS: The designed 3D printed model of the kidney completely
      reproduces the individual features of the intra-renal structures of the
      particular patient. During the training, all the main stages of PCNL were
      performed successfully: the puncture, dilation of the nephrostomy tract,
      endoscopic examination, intra-renal lithotripsy. CONCLUSION: Our proprietary 3D
      printed simulator is a promising development in the field of endourologic
      training and preoperative planning in the treatment of complicated forms of
      urolithiasis.

PMID- 29634128
TI  - [Changes in the concentration of urolitiasis markers depending on stone-forming
      activity in patients with recurrent urolithiasis].
AB  - : The study aimed to investigate the changes in the concentration of bikunin,
      osteopontin, and nephrocalcin, depending on the changes in the renal stone
      forming activity in patients with recurrent urolithiasis. MATERIALS AND METHODS:
      The study comprised 152 patients with recurrent calcium oxalate stones at various
      localizations. Patients of the study group (n=78) were administered complex
      preventive treatment (water load, Blamaren, thiazide diuretics, oral calcium
      supplementation) aimed at reducing the activity of urolithiasis. Patients of the
      control group (n=74) received no treatment. The studied parameters included
      concentrations of urine bikunin, osteopontin, and nephrocalcin in using ELISA.
      The follow-up period was six months. RESULTS: By the end of the follow-up, the
      bikunin concentration in the control group was significantly higher than in the
      study group (7.0+/-0.81 mg/ml vs. 3.28+/-0.86 mg/ml, respectively, p<0.05) while
      osteopontin level was significantly lower (2.4+/-0.39 mg/ml vs. 3.4+/-0.36 mg/ml,
      p<0.05). The nephrocalcin concentrations during the follow-up period did not
      change significantly (p>0.05). The presence of hypercalciuria did not lead to
      significant changes in the concentration of stone formation inhibitors.
      DISCUSSION: The increase in bikunin concentration in control patients is
      associated with an increase in the expression of this stone formation inhibitor
      due to the rise in the urolithiasis activity. Reduction in the osteopontin
      concentration in patients with high urolithiasis activity is a consequence of
      osteopontin being a constituent of calcium oxalate stones. CONCLUSION: In
      patients with calcium oxalate urolithiasis, testing for urine concentrations of
      bikunin and osteopontin as potential markers can be used to estimate the risk of
      stone recurrence.

PMID- 29634129
TI  - [Time to recurrence after complete removal of calculi from different parts of the
      urinary system. five-year follow-up study].
AB  - INTRODUCTION: The usage of minimally invasive technologies (MIT), such as:
      extracorporeal shock wave lithotripsy (ESWL), transurethral ureterolithotripsy
      (URS), retrograde intrarenal surgery (RIRS), percutaneous nephrolithotripsy
      (PNL), allows to remove the stones from the calyx and pelvis system with 71- 96%
      of patients, and those from the ureter in 96.2% cases. However, a high incidence
      of stone recurrences (35-75%) demands the necessity of repeated lithotripsies and
      the search of the most appropriate methods of lithotripsy for reduction this
      indicator. The main goal. To determine the number of patients with recurrence of
      stone formation during five years after different types of lithotripsy in
      different parts of the urinary system. MATERIALS AND METHODS: The results of the
      process were analyzed with 491 patients, who had been devided into two groups:
      group I - 358 patients suffering from the concrements of the ureter; group II -
      133 patients having stones in kidney. RESULTS: According to the age criterion,
      the sample data did not differ from each other (50 years for both groups
      (p=0.576). The initial number of lithotripsies with complete removal of stones
      was 80.7% in group I and 70.7% in gr. II, the repeated lithotripsy with usage of
      the same method was 5.9% and 12.8%, respectively. The usage of an additional
      method in repeated lithotripsy was necessary in 13.4% and 16.5% of cases
      respectively. There were differences between the sizes of stones in groups
      (p<0.0001), besides both groups showed the difference in recurrence time of stone
      formation (p=0,014). In gr. I weak negative correlation (-0.28) between age and
      time of recurrence was revealed. The age difference between men and women in both
      groups (p=0.00001 and p=0.0492, respectively) was found. There occurred
      differences in the size of stones in men and women groups (p=0.0000001 and
      p=0.0000001, respectively) and in the time of recurrence between men and women in
      I gr. (p=0.043). Most of stones were compose of CaOx, the second most important
      element was Uric Acid. All this testifies to peculiarities of the diet in the
      region of residence of the patients under control - the Republic of
      Bashkortostan, where people generally use meat and milk products. DISCUSSION: The
      usage of MIT opened the possibility of complete stone removal from the urinary
      system with the most sparing technique. The lithotripsy of stones with any
      composition having been conducted, additional stone crushing is carried out with
      21-59% of patients within 5 years. The investigation of patients detected a great
      number of recurrences of stones in the kidney stones group. CONCLUSION: 1. After
      lithotripsy the recurrences during two years did not exceed 4,2% with patients in
      gr. I and 8,2% in gr. II patients. 2. Significant dependence of recurrent stone
      formation of gender composition was identified in gr. I and the time of
      recurrence was less in women. 3. The quantity of CaOx urolithiasis corresponds to
      global indicators. However, a large number of stones with Uric Acid in the
      composition indicates possible peculiarities of the patients diet. 4. The highest
      number of recurrences were in patients with CaOx (42.3%) and CaOx with CaF in the
      composition (23.1%), and in third place were patients with uric acid stones
      (19.2%).

PMID- 29634130
TI  - [Bladder hydrodistension in treating patients with interstytial cystitis/ bladder
      pain syndrome].
AB  - : This study aimed to evaluate the effectiveness of bladder hydrodistension in
      the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS), depending
      on the duration of the procedure. MATERIALS AND METHODS: The study comprised 71
      women aged 51.6+/-8.3 years with a 5.2+/-2.3 year history of IC/BPS. All patients
      underwent bladder hydrodistension (BH). Depending on the duration of BH, patients
      were divided into 4 groups. The distension time in group 1 (n=10), group 2
      (n=20), group 3 (n=20) and group 4 (n=21) was 1 min, 2 min, 4 min and 6 min,
      respectively. The treatment effectiveness was assessed 1 month after BH by
      subjective assessment of patients, Pelvic Pain and Urgency/Frequency (PUF)
      Patient Symptom Scale questionnaire, a visual analog pain scale (VAS), and
      voiding diaries. RESULTS: At one month after BH, positive effect was observed in
      32 (45.1%) patients. In groups 1, 2, 3 and 4 the treatment was effective in 20%,
      55%, 45% and 47.6% of patients, respectively. Clinical effectiveness of BH with
      distension time of 1 min was significantly lower than that of 2, 4, and 6 min. At
      the same time, we did not find significant differences in the effectiveness of
      this procedure with distension time of 2, 4 and 6 min. CONCLUSION: The results of
      this study suggest that BH is an effective treatment in patients suffering from
      IC/BPS. At the same time, they show that the distension time of 2 min. is optimal
      from the point of view of clinical effectiveness, since the longer duration of
      the procedure is excessive, and the shorter time is insufficient.

PMID- 29634131
TI  - [NefroCAPS phytolysin in complex management of women with chronic recurrent
      cystitis].
AB  - RELEVANCE: Recurrent lower urinary tract infections (UTI) in women are one of the
      most challenging problems of modern urology, which is associated both with their
      high incidence and increasing resistance of uropathogens to antibacterial drugs.
      Due to this fact, the phytotherapy of infectious and inflammatory diseases of the
      urinary tract has received increased attention. AIM: To investigate the
      effectiveness of Phytolysin nefroCAPS in the complex management of women with
      chronic recurrent cystitis. MATERIALS AND METHODS: 50 women with chronic
      recurrent cystitis underwent a complex examination. They were divided into two
      groups depending on the treatment they received. Patients of the 1st group (n=27)
      received a combination therapy: fosfomycin (monural) 3 g (single dose) and
      Phytolysin nefroCAPS one capsule three times daily for three months. Patients of
      the 2nd group (n=23) were administered a single 3-g dose of fosfomycin (monural).
      RESULTS: Follow-up examinations were performed 1, 3 and six months after
      initiation of the treatment. In patients of the 1st group, clinical
      manifestations of the disease disappeared earlier, and they had fewer recurrences
      than the patients of the 2nd group. Also, bacteriological study of urine showed a
      more persistent antimicrobial effect among patients of the 1st group. CONCLUSION:
      In patients with chronic recurrent cystitis, plant-based preparation Phytolysin
      nefroCAPS administered concurrently with an antibacterial drug is more effective
      than antibiotic monotherapy.

PMID- 29634132
TI  - [New approach to diagnosis, immunophenotypic verification and prognostic
      prediction for renal angiomyolipoma].
AB  - : Renal angiomyolipoma (AML) is a rare benign neoplasm of mesenchymal origin. AML
      incidence varies from 0.3 to 5%, while women suffer four times more often than
      men. In most cases, renal AML measures less than 4 cm, is asymptomatic and
      detected accidentally with computed tomography or ultrasound. A histological
      variant of AML need to be verified to choose management strategy and reduce the
      risk of complications. Histological and immunohistochemical assessment of biopsy
      and surgical specimens has an essential diagnostic value in determining the type
      and subtypes of renal neoplasms and the risk of malignancy. The study aimed to
      investigate pathomorphological and prognostic features (immunohistochemical
      characteristics) of renal AML. MATERIALS AND METHODS: Patients (n=42) with CT
      detected renal neoplasms underwent partial nephrectomy. The majority (n=34) of
      patients was admitted to the hospital urgently, often without symptoms (n=23).
      The surgical specimens studied were examined using light microscopy and
      immunohistochemistry analysis with primary mouse monoclonal antibodies to HMB-45,
      Melan-A, -SMA, S-100 and SC (Novocastra, UK). RESULTS: All specimens showed
      morphological characteristics typical of AML and a positive response to
      antibodies against HMB-45 (ve +/3; 99.6+/-0.3%), Melan-A (ve + / 2, 89.6+/-4.3%)
      and SMA (ve + 2; 70.1+/-2.9%) and exhibited no staining with antibodies against S
      100 and SK. CONCLUSION: Morphological study of renal AML shows that the tumor is
      benign, therefore partial nephrectomy, in our opinion, should be considered as an
      alternative to radical nephrectomy, including for sporadic giant renal AML.

PMID- 29634133
TI  - [Complications of the holmium laser enucleation of prostate for benign prostatic
      hyperplasia].
AB  - INTRODUCTION: With growing experience in the HoLEP, it can replace TURP as the
      "gold standard" for the surgical management of BPH, and therefore this technique
      is the most studied surgical modality. Despite the proven effectiveness of HoLEP
      in the treatment of patients with BPH, its widespread use has been associated
      with both intra- and postoperative complications. AIM: To improve the results of
      surgical management of patients with BPH. MATERIAL AND METHODS: The study
      comprised 310 patients who underwent HoLEP for BPH. HoLEP was performed using the
      Gillings technique. INCLUSION CRITERIA: presence of LUTS (Qmax<15 ml/s, Qav<10
      ml/s, presence of residual urine, I-PSS score> 5, QoL score> 2), absence of an
      active inflammatory process of the urogenital organs. RESULTS: Intraoperative
      complications included severe hemorrhage in 16 (5.2%), the bladder wall injury in
      17 (5.5%) and the ureteral orifice injury in 2 (0.6%) patients. 275 (88.7%) had
      no intraoperative complications. Early postoperative complications included fever
      in 4 (1.3%), the bladder tamponade that required cystoscopy and evacuation of
      blood clots in 7 (2.3%) and acute urinary retention in 36 (11.8%) patients. 263
      (84.6%) patients had no postoperative complications. Long-term postoperative
      complications comprised urinary incontinence in 39 (12.6%) patients and urethral
      strictures requiring surgical treatment in 9 (2.9%) patients. There were no long
      term complications in 262 (84.5%) patients. CONCLUSION: HoLEP is an effective and
      safe surgical modality for treating patients with BPH with minimal complications,
      suitable for any size of the prostate.

PMID- 29634134
TI  - [Nephrotuberculosis and urolithiasis].
AB  - INTRODUCTION: Urolithiasis and nephrotuberculosis, due to the similarity of the
      radiographic patterns, share the same differential diagnosis list. The study
      aimed to analyze the incidence of co-occurrence of nephrotuberculosis and
      urolithiasis and to determine the impact of urolithiasis on the clinical course
      of renal tuberculosis. MATERIAL AND METHODS: This open cohort retrospective study
      comprised 843 patients with renal tuberculosis and 245 patients with
      urolithiasis. 1088 medical records were analyzed to identify cases with co
      occurrence of these two diseases and determine the clinical presentation of renal
      tuberculosis, urolithiasis, and the comorbid state. Also, patients with pulmonary
      tuberculosis (44), urogenital tuberculosis (17), and chronic nonspecific
      pyelonephritis (12) were tested for serum concentration of total calcium and
      phosphorus. RESULTS: Of 843 patients with renal tuberculosis, 39 (4.6%), had
      concomitant nephrolithiasis. The combination of urolithiasis with
      nephrotuberculosis manifested by more severe symptoms; these patients had a more
      than two-fold risk of tuberculosis recurrence. Except for the incidence of renal
      colic and dysuria, the clinical manifestations of urolithiasis and
      nephrotuberculosis did not differ statistically significantly. Prolonged
      infectious and inflammatory process in the kidneys resulted in an increase in the
      excretion of oxalates, which was more pronounced in patients with nonspecific
      pyelonephritis (p<0.05). A three-month course of antituberculosis chemotherapy
      resulted in a 36.2% increase in the excretion of oxalates in patients with
      urotuberculosis (p<0.05). Excretion of uric acid also significantly increased
      after a three-month intake of antituberculosis drugs. CONCLUSION: In our study,
      the incidence of concomitant urolithiasis and urogenital tuberculosis was low
      (4.6%), but comorbidity significantly complicated the clinical course of the
      disease and worsened the prognosis of nephrotuberculosis. Antituberculosis
      polychemotherapy increases the risk for formation of urinary stones. Prevention
      of urolithiasis in patients with urogenital tuberculosis warrants further
      investigation.

PMID- 29634135
TI  - [Quality of life in patients with lower urinary tract symptoms after TURP for
      benign prostatic hyperplasia].
AB  - INTRODUCTION: To date, the gold standard for the surgical management of BPH is
      transurethral resection of the prostate (TURP). Most patients who undergo TURP
      for BPH experience immediate effects and complete relief of lower urinary tract
      symptoms and do not need further urological care. However, some patients after
      this operation have some level of persistent residual lower urinary tract
      symptoms, which may require additional therapy. AIM: To investigate voiding
      function and the need for medical therapy in patients who underwent TURP for LUTS
      due to BPH. MATERIALS AND METHODS: This study was performed as an anonymous
      survey among male patients presenting to a urology clinic. During the visit, the
      patients were offered to fill out I-PSS and SF-36 questionnaires. Also, they were
      asked about their socio-economic status, history of BPH, their perception of
      surgery and the postoperative period up to the day of the interview, presence or
      absence of symptoms of voiding dysfunction and any drug therapy at the time of
      the interview or after surgery. The patients also rated the severity of the
      symptoms using the IPSS questionnaire. The study comprised patients after 12
      months to 3 years following successful TURP for LUTS due to BPH. A total of 1100
      questionnaires were forwarded to researchers for interviewing patients who
      underwent TURP for prostatic hyperplasia. RESULTS: After collecting and reviewing
      all the questionnaires, 921 questionnaires were found eligible. The findings of
      the survey showed that a significant proportion of patients who underwent TURP
      require a long-term postoperative medical therapy. At the same time, in the
      Russian Federation, there are no standard approaches to medical management of
      this category of patients.

PMID- 29634136
TI  - [Combination therapy in the management of urinary disorders after transurethral
      resection of the prostate].
AB  - INTRODUCTION: Surgery in patients with large prostates due to benign prostatic
      hyperplasia (BPH) results in severe dysuria manifesting as frequent or urgent
      need to urinate and urinary incontinence. Traditionally, these conditions are
      treated with alpha blockers. Recently, alpha-blockers and the anticholinergic
      combination have been used showing additional advantages. This study aimed to
      investigate the comparative effectiveness of monotherapy versus combination
      therapy in the treatment of postoperative dysuria in BPH patients with large
      prostates undergoing transurethral surgery. MATERIALS AND METHODS: From September
      2016 to March 2017, 94 BPH patients with prostates greater than 100 cc underwent
      transurethral surgery at the Department of Urology of D.D. Pletnev Clinical
      Hospital; 22 patients had exclusion criteria. In the postoperative period, 36
      patients received 0.4 mg of modified release tamsulosin (Omnik) for a month, and
      36 patients were administered controlled release tablets tamsulosin 0.4 mg +
      solifenacin 6 mg (Vezomni) as fixed-dose combination therapy. At one month
      postoperatively, patients were asked to rate their symptoms on a visual analogue
      scale and fill out I-PSS and QoL questionnaires. Preoperative parameters of the
      groups were: visual analogue scale scores were 5.1 and 5.2, I-PSS scores were 24
      and 24.2, QoL scores were 4.5 in both groups. Prostate volumes were 114 and 118
      cc; maximum urinary flow rates were 7.7 vs. 7.5 ml/sec, residual urine volumes
      were 110 vs. 105 ml, respectively. RESULTS: Visual analogue scale scores were 6.5
      versus 9.2 points, I-PSS scores were 16.3 versus 12.1. The patients of the second
      group had greater mean micturition volume (150 versus 240 ml); other variables
      did not differ statistically significantly between the groups. Adverse reactions
      were mild, and drugs were not discontinued in any case. CONCLUSION: In BPH
      patients with dysuria after transurethral resection of large prostates, Vezomni
      administration results in a better quality of life due to an improvement in
      urgency and nocturia.

PMID- 29634137
TI  - [Effect of transderrmal testosterone on the quality of life of men with androgen
      deficiency and chronic prostatitis in routine clinical practice].
AB  - AIM: To evaluate the effect of Androgel on the quality of life of patients with
      androgen deficiency (hypogonadism) and chronic prostatitis in everyday practice.
      MATERIALS AND METHODS: This open multicenter observational non-interventional
      study comprised 401 men with testosterone deficiency and chronic prostatitis who
      were treated with topical applications of 1% testosterone gel of (Androgel) at a
      dose of 50 or 100 mg in routine clinical practice for three months. The primary
      endpoint was the health related quality of life. Also, the patients filled out
      AMS, I-PSS, NIH-CPSI questionnaires to assess the quality of life related to
      chronic prostatitis, lower urinary tract symptoms, and aging. Secondary endpoints
      included changes in the overall score of the International Index of Erectile
      Function (IIEF-5), changes in body weight and waist circumference, the reasons
      for treatment discontinuation and any adverse events that occurred during
      treatment. RESULTS: Mean total testosterone levels at baseline and three months
      were 9.5 (95% CI 9.2-9.7) nmol/L and 16.5 (95% CI 16.1-16.9) nmol/l (p<0.001),
      respectively. There were statistically significant (p<0.001) differences in
      scores on all questionnaires. Mean scores at baseline and at three months for
      AMS, IIEF-5, I-PSS, NIH-CPSI questionnaires were 44.6 (95% CI 43.2-45.9) and 25.8
      (95% CI 24.8-26.7); 12.7 (95% CI 12.2-13.2) and 19.3 (95% CI, 18.8-19.8); 14.5
      (95% CI 13.7-15.3) and 5.6 (95% CI 5.2-6.1); 27.8 (95% CI 26,5-29.1) and 10.0
      (95% CI 9.1-10.9), respectively. There were positive changes in body weight and
      waist circumference: at baseline and three months these parameters were 95 (95%
      CI 93.6-96.3) and 91.4 (95% CI 90.1-92.7) kg and 102.9 (95% CI 101.8-104.1) and
      98.3 (95% CI 97.3-99.3) cm, respectively. No clinically significant adverse
      events were observed during follow-up. CONCLUSIONS: Transdermal therapy with 1%
      testosterone gel (Androgel) is highly effective and safe in the management of
      androgen deficiency (hypogonadism). Its use in patients with chronic prostatitis
      and hypogonadism results in an improvement in low urinary tract symptoms,
      symptoms of chronic prostatitis, alleviates pelvic pain and thus leads to
      significant improvements in the quality of life.

PMID- 29634138
TI  - [Species composition and molecular-genetic characteristics of antibiotic
      resistant strains of gram negative bacteria isolated from patients of a hospitals
      urology department].
AB  - AIM: To analyze the composition and molecular mechanisms of antibiotic resistance
      of Gram-negative bacteria - pathogens of urinary tract infections (UTIs) in adult
      patients living in the city of Almaty. MATERIALS AND METHODS: The study examined
      the etiological composition and antibiotic susceptibility of clinically
      significant isolates of bacteria and fungi ( more or equal 103) isolated from the
      urine of the patients of the Department of Urology of the Almaty city Central
      Clinical Hospital No. 12. The production of extended-spectrum beta-lactamases
      (ESBL) in antibiotic-resistant strains was determined using a phenotypic method
      with the double disk test. Detection of class A genes for cultures with confirmed
      ESBL phenotypes (TEM-1, CTX-M1, SHV, OXA) and carbapenemases of class B metallo-
      lactamases (VIM-2) genes was performed by PCR. RESULTS: Among the isolates
      obtained from patients, the species of Enterobacteriaceae family in the
      etiological composition of the UTI pathogens comprised 44.8% including E. coli
      (31%), K. pneumoniae (4.6%). The most effective drugs against all types of
      Enterobacteria were carbapenems (96.3-100%). E.coli showed highest sensitivity to
      nitrofurantoin (96.3%), amikacin (92.6%) and cefoxitin (81.5%). The high rate of
      resistance to III-IV generation cephalosporins among of E. coli (44.4%) and K.
      pneumoniae (50%) species was due to the production of ESBL types CTX-M1 and OXA.
      The proportion of non-fermenting Gram-negative bacteria in the etiological
      composition of UTI pathogens was 3.5%. Among them, there was a strain producing
      the metal -lactamase (VIM-2), characterized by absolute resistance to antibiotics
      of all classes, including carbapenems. CONCLUSION: The findings on sensitivity
      profiles and molecular genetic mechanisms of resistance of Gram-negative
      uropathogens are unique for the Almaty region provides the rationale for
      developing a local strategy for rational antibiotic therapy. Timely
      microbiological diagnosis and strict adherence to infection control in a specific
      hospital are the only way to contain the spread of ESBL and metal -lactamase.

PMID- 29634139
TI  - [Comparative analysis of one- and two-stage augmentation urethroplasty with
      dorsal INLAY buccal graft for extended stricturesof spongious urethra].
AB  - INTRODUCTION: Urethral reconstructive surgery is in constant development. At
      present, reconstructive urethroplasty with buccal mucosa is increasingly being
      used. The study aimed to compare the results of a one- and two-stage augmentation
      urethroplasty with dorsal inlay buccal graft for strictures of the spongious
      urethra. MATERIALS AND METHODS: The study comprised 72 patients aged 19-64 with
      urethral strictures 3-18 cm long. In 34 (47.2%) patients, the stricture was
      localized in the penile urethra, in 30 patients (41.6%) in the penile-bulbous
      urethra and in 8 patients (11%) in the bulbous urethra. All patients underwent
      augmentation urethroplasty with dorsal inlay buccal graft. The results were
      evaluated separately in 55 (76.4%, group 1) and 17 (23.6%, group 2) patients who
      underwent one-stage and two-stage surgery, respectively. RESULTS: The incidence
      rate of early postoperative complications was higher after one-stage (23.6%)
      compared two-stage surgery (11.8%) (p<0.05). Hematomas, wound dehiscence and
      urethrocutaneous fistulas were observed only after single-stage surgery. Primary
      healing of extensive strictures following augmentation urethroplasty with dorsal
      inlay buccal graft was achieved in 88.9% of patients; treatment effectiveness in
      the group 1 was 89.1%, in the group 2 - 88.2% (p>0.05). The final effectiveness
      of the operation, achieved with the use of additional surgical interventions, is
      estimated at 98.6%. CONCLUSION: The results of augmentation urethroplasty with
      dorsal inlay buccal graft do not depend on the number of stages, but fewer
      complications accompany two-stage surgery.

PMID- 29634140
TI  - [Fibroblast growth factor-21 as a marker of premature aging in young and middled
      aged men with type 2 diabetes].
AB  - AIM: To investigate the impact of fibroblast growth factor 21 (FGF-21) on the
      severity of androgen deficiency in young and middle-aged men with type 2 diabetes
      mellitus. MATERIALS AND METHODS: The study comprised 100 men with type 2 diabetes
      mellitus, cardiovascular multi-morbidity, obesity and androgen deficiency (study
      group) and 20 healthy men aged 35-50 years. The study group was further divided
      into two subgroups. Patients of the subgroup 1 received the standard treatment
      for type 2 diabetes and cardiovascular disease. Patients of the subgroup two were
      treated with conventional therapy concurrently with testosterone undecanoate. The
      baseline examination included the following parameters: glycated hemoglobin,
      total testosterone, prolactin, thyroid stimulating hormone and blood FGF-21. At
      nine months after the treatment, the blood levels of glycated hemoglobin, FGF21
      and testosterone were re-examined. The evaluation of the severity of androgen
      deficiency was carried out using the ICEF-5 questionnaire and the Aging Males
      Symptoms scale (AMS). RESULTS: In the study group, the mean FGF-21 level was 2.7
      times higher, and the total testosterone level was 2-2.5 times lower than in the
      control group (p<0.05). A negative correlation was found between the blood levels
      of FGF-21 and total testosterone (r=-0.41, p<0.05). At nine months post
      treatment, the subgroup with testosterone undecanoate administered as add-on
      therapy showed a further decrease in FGF-21 levels and improved androgen
      deficiency symptoms. DISCUSSION: FGF-21 is one of the markers for type 2
      diabetes, cardiovascular multi-morbidity, obesity and androgen deficiency. Given
      the association of FGF-21 with androgen deficiency, it can be assumed that FGF-21
      plays a role in premature aging. Treatment of androgen deficiency as add-on
      therapy to the standard treatment of this category of patients improves their
      prognosis and the quality of life. CONCLUSION: Young and middle-aged men with
      type 2 diabetes should undergo regular screening for androgen deficiency with the
      purpose of its early diagnosis and timely treatment. The detection of elevated
      levels of FGF-21 in young and middle-aged men with type 2 diabetes mellitus and
      cardiovascular multi-morbidity may indicate premature aging and requires
      preventive measures.

PMID- 29634141
TI  - [Evaluation of testosteronemia in men undergoing surgery for urethral
      strictures].
AB  - INTRODUCTION: Testosterone plays an important role in the functioning of various
      organs and systems of the male body. Its diagnostic and prognostic values are
      studied both in urological diseases and in the patients undergoing non-urologic
      surgery. AIM: To investigate changes in testosterone level in patients with
      urethral strictures (US) depending on its baseline level, the cause of US, the
      age of patients and the number of surgeries. MATERIALS AND METHODS: The study
      comprised 30 patients aged 19-63 years with traumatic (76.7%) and inflammatory
      (23.3%) US. Primary and recurrent US were diagnosed in 25 (83.3%) and 5 (16.7%)
      patients, respectively. Nineteen (63.3%) patients underwent excision and primary
      anastomosis, while replacement urethroplasty was performed in 11 (36.7%)
      patients. In addition to the standard diagnostic work-up, all patients were
      tested for total serum testosterone 24 hours prior to surgery and at 1, 3, 7, 14
      days after the operation. RESULTS: 33.3% of men with US had a testosterone
      deficiency in the absence of any testicular or endocrine injuries and diseases.
      Surgery was associated with a drop in testosteronemia in 83.3% of patients. The
      degree of postoperative testosterone level decline and its changes were
      significantly influenced by the age of patients and the number of operations. Men
      who had baseline testosterone deficiency and underwent repeat surgeries remained
      in a hypogonadal state throughout the postoperative period. CONCLUSION:
      Investigating the clinical value of testosterone in men with US and the risks of
      their surgical treatment associated with testosterone deficiency will provide
      insight into the role of testosterone in the treatment of this condition and the
      decision-making regarding pharmacological correction of testosterone deficiency
      in patients undergoing surgery for US.

PMID- 29634142
TI  - [Combination drug therapy in patients with BPH].
AB  - : Introuction. One of the risk factors for LUTS is an infravesical obstruction,
      which is most often caused by benign prostatic hyperplasia (BPH). BPH symptoms
      are formed due to three components: static (mechanical), dynamic, and impaired
      functional capacity of the bladder. Medical treatment with 1-blockers decreases
      the outflow obstruction. 5-alpha reductase inhibitors are used to inhibit the
      static component of BPH. AIM: To investigate the effectiveness of various
      modifications of medical therapy of BPH using -blockers and 5-reductase
      inhibitors and combinations thereof. MATERIALS AND METHODS: The study comprised
      90 BPH patients who were divided into three groups, with each group containing 30
      people. Patients of group I, II and III received monotherapy with -blockers, a
      combination of 5-reductase and -blockers, and fixed-dose combination drug
      Duodart, respectively. Evaluation of the treatment effectiveness included filling
      out voiding diaries, completing the I-PSS and QL questionnaires, uroflowmetry,
      transrectal ultrasonography of the prostate and estimation of the incidence of
      adverse effects. Also, compliance with the treatment was evaluated, and the
      number of patients who had episodes of acute urinary retention and required
      surgical treatment during the 12 month treatment course was registered. RESULTS:
      Compared to monotherapy, combination therapy with -blockers and 5-reductase
      inhibitors more effectively reduces the LUTS, increases Qmax and prevents the
      disease progression, which manifests in a lower incidence of AUR and fewer
      surgical interventions in groups II and III. However, the combination therapy can
      be associated with some side effects. Patients who received fixed-dose
      combination drug Duodart had a greater compliance rate than patients on the
      combination of drugs, which, in our opinion, is associated with fewer cases of
      AUR and surgical interventions. CONCLUSION: The use of Duodart in patients with
      BPH effectively alleviates LUTS and reduces the risk of the disease progression,
      which manifests itself in a reduced number of complications and thereby
      contributes to improving the quality of life of patients.

PMID- 29634143
TI  - [Afalaza in the management of patients with chronic pelvic pain syndrome].
AB  - INTRODUCTION: Currently, chronic pelvic pain syndrome (CPPS) is one of the most
      prevalent urological diseases, but due to the multifactorial nature of the
      disease and the lack of consensus on its pathogenesis, the issue of adequate
      therapy remains open. Since the vascular factor plays the major role in the
      pathogenesis of CPPS, we hypothesized that this category of patients has
      microcirculatory disturbances of the prostate. AIM: Detection of microcirculatory
      disturbances of the prostate, their correction, and evaluation of the effect on
      the course of CPPS. MATERIALS AND METHODS: The study comprised 60 healthy,
      sexually active men with clinical manifestations of CPPS lasting from 6 months to
      5 years. After a comprehensive examination, all patients received Afalaza 2
      tablets twice daily for 16 weeks. At the end of week 16, patients were re
      examined. RESULTS: In patients with CPPS, therapy with Afalaza resulted in a
      significant improvement in microcirculation in the prostate thus leading to the
      reduction of the severity of disease manifestations.

PMID- 29634144
TI  - [Initial experience in clinical application of thulium laser contact lithotripsy
      for transurethral treatment of urolithiasis].
AB  - INTRODUCTION: The choice of an effective and safe method of disintegration of
      stones in upper and lower urinary tract is very important in the context of
      continuous scientific and technological progress. In current clinical urological
      practice, various lithotriptors with rigid and flexible probes are used for
      contact disintegration of stones, having both advantages and disadvantages. This
      study aimed to analyze the first results of the clinical application of the
      native Tm: fiber Urolaz laser (STA IRE-Polyus, Russia) for contact transurethral
      lithotripsy. MATERIALS AND METHODS: The study comprised 56 patients who underwent
      transurethral contact thulium laser lithotripsy for 68 stones of the upper and
      lower urinary tracts between April and September 2017. Forty-four patients had
      kidney and ureteral stones, and twelve patients had urinary bladder stones.
      Twenty-four kidney stones were removed by retrograde intrarenal surgery using
      ureteral casing, flexible ureteropyeloscope and thulium laser, 32 stones in
      various ureteral segments - by rigid contact thulium laser ureterolithotripsy and
      12 bladder stones - by thulium laser cystolithotripsy. The size of the upper
      urinary tract stones varied from 0.6 to 1.8 cm, bladder stones measured from 1.1
      to 3.5 cm. Also, experimental studies were carried out to investigate the effects
      of the fiber thulium and holmium laser on the stone displacement and temperature
      environment during lithotripsy. RESULTS: Full stone fragmentation was achieved in
      100% of patients. 47.7% of patients required additional lithoextraction of
      fragments; there was no retrograde migration of large stones. The mean duration
      of stone disintegration was 19 minutes. Postoperatively, 15.9% of patients had an
      exacerbation of pyelonephritis, which was successfully managed by conservative
      measures. The mean postoperative hospital stay was 2.4+/-1.1 days. At follow-up
      examination 4-6 weeks after surgery, one patient was found to have a residual
      symptomatic ureteral stone, which required extracorporeal short-wave lithotripsy.
      The experimental study showed that fiber thulium laser lithotripsy produced much
      less propulsion of artificial stone than Holmium laser lithotripsy. With the use
      of therapeutic power, neither of the lasers resulted in "dangerous" rises of the
      washing fluid temperature during stone disintegration. CONCLUSION: Using the
      universal thulium laser system "Urolaz" provides a significant improvement in the
      effectiveness of endourologic upper urinary tract interventions and significantly
      reduces the likelihood of intraoperative trauma and postoperative complications,
      which contributes to improving the quality of specialized urological care.

PMID- 29634145
TI  - [Results of laparoscopic ureterolithotomy depending on the type of laparoscopic
      approach and location of the stone].
AB  - AIM: To investigate the results of laparoscopic management of patients with
      ureterolithiasis, depending on the type of laparoscopic approach and location of
      the stone. MATERIALS AND METHODS: This study is a retrospective analysis of 30
      ureterolithiasis patients who underwent laparoscopic ureterolithotomy from 2010
      to 2015. Patients were divided into four subgroups depending on the type of
      laparoscopic approach - transperitoneal (n=17) and retroperitoneal (n=13) and on
      location of stones - upper ureteral stone (n=20) and mid ureteral stone (n=10).
      The patients comprised 23 (76.7%) men and 7 (23.3%) women aged from 18 to 68
      years (mean age 46.2+/-2.3 years). 15 patients had stones in the right and 15 in
      left ureters. The groups were comparable by sex, age, the severity of
      hydronephrosis, body mass index, duration of urolithiasis, comorbidities and
      previous surgeries (p>0.05). RESULTS: There were no deaths, conversion to open
      surgery or intraoperative complications. The only statistically significant
      difference between transperitoneal and retroperitoneal approaches was the absence
      of postoperative complications (p<0.05). The duration of drainage and hospital
      stay was significantly shorter in patients with mid ureteral stone than in
      patients with upper ureteral stone (p<0.05). CONCLUSION: Surgical management of
      patients with ureterolithiasis of various locations using laparoscopic
      ureterolithotomy by different approaches showed positive results of in all cases
      thus indicating high clinical effectiveness of this method.

PMID- 29634146
TI  - [Total epispadias of duplicated urethra in boys].
AB  - The article reports on two cases of the total epispadias of duplicated urethra
      with and without penile duplication. The authors describe the clinical
      presentation, diagnosis, and treatment. Duplicated urethra with epispadias both
      with and without penile duplication must be removed. At the same time, it is
      necessary to restore the patency of the lower duplicated urethra.

PMID- 29634147
TI  - [Urethral leiomyoma].
AB  - In urology practice, leiomyoma of the urinary bladder is considered a rare tumor.
      Urethral leiomyoma is even more unusual. This article is a case report of a very
      rare benign tumor originating from the smooth muscles of the urethra causing
      obstructive voiding in a woman.

PMID- 29634148
TI  - [Methods of traditional chinese medicine in the treatment of patients with
      interstitial cystitis/bladder pain syndrome].
AB  - In recent years, there has been an increasing interest in alternative
      (complementary) treatments of interstitial cystitis/bladder pain syndrome
      (IC/BPS). This is due both to the high incidence of IC/BPS and to a lack of
      effectiveness of conventional treatments. One of the directions of alternative
      therapies is a traditional Chinese medicine using a special diet, various animal
      and plant-derived medicines, breathing exercises and acupuncture. This review
      analyzes the accumulated experience in using traditional Chinese medicine in the
      treatment of patients with IC/BPS. The presented data indicate that these methods
      appear to be promising, since they are effective in a significant number of
      patients, lead to an improvement in their quality of life, are non-invasive and
      well tolerated. However, due to the lack of clinical studies, the efficacy of
      this treatment modalities needs to be confirmed.

PMID- 29634149
TI  - [Use of buccal graft for the management of ureteral strictures].
AB  - This review analyses of the results of using buccal mucosa graft for the
      management of ureteral strictures. The authors identified sixteen original
      studies presenting the results of ureteral reconstruction using buccal grafts. Of
      them, twelve, three and one studies used the open, robotic and laparoscopic
      technique, respectively. Open surgery was performed 44 times in 42 patients (2
      patients underwent bilateral ureteroplasty) with an average ureteral stricture
      length of 6.0 (2.5-11) cm. Ureteral patency was restored in 93.2% (41/44) of
      patients with an average follow-up of 26 (3-85) months. The robotic technique was
      used in 18 patients with an average ureteral stricture length of 3.25 (1.5-6) cm.
      Positive results after similar operations were achieved in 88.9% (16/18) of
      patients with an average follow-up of 15 (4-30) months. The laparoscopic
      technique was used only once for a ureteral stricture measuring 3 cm in length
      and was characterized as successful at a follow-up of 9 months. All surgical
      modalities were associated with minimal risk of early and late postoperative
      complications. The review results suggest that buccal substitution ureteroplasty
      can be regarded as an advantageous alternative to more complicated surgical
      procedures associated with greater complication rates (ileal ureteral
      substitution and kidney autotransplantation) used for long ureteral strictures.

PMID- 29634150
TI  - [Clinical implications of dual-energy computed tomography in the diagnosis and
      treatment of urolithiasis].
AB  - Urolithiasis (urolithiasis) is one of the most common urologic diseases with an
      estimated prevalence of no less than 3% in the population, usually affecting
      active working-age patients of 30-50 years. Taking into account major public
      health and economic significance of this problem, there is the need for the
      development of effective modern diagnostic techniques. Rapid medical
      technological advances of the past two decades have led to the wide spread use of
      minimally invasive surgery the management of urolithiasis. Nevertheless, surgical
      intervention only removes the result of a long pathological process and does not
      change its course. Thus, there is a need for a detailed understanding of the
      etiology, epidemiology, and pathogenesis of urolithiasis. Diagnostic imaging
      plays a key role in the diagnosis of urolithiasis. Multislice spiral computed
      tomography (MSCT) is the gold standard for the diagnosis of urolithiasis. It
      provides information about the size, location, and density of the calculus. Over
      the past decade, the use of dual-energy computed tomography (DECT) in urological
      practice has been widely discussed in the international and domestic literature.
      One of the main advantages of DECT is the ability to determine the chemical
      composition of urinary stones. Previous studies have reported a high diagnostic
      value of the method, including the ability to predict treatment outcomes.
      However, the shortcomings of the method and the absence of standardized
      examination protocols leave a wide field for further research. This article
      reviews major distinctive features of using DECT in the diagnosis of
      urolithiasis.

PMID- 29634151
TI  - [Current view on the pathogenesis of varicocele and the problem of its
      recurrence].
AB  - The clinical signs of varicocele typically emerge during the puberty. Varicocele
      is found in 15% of men in the general population and 25-35% and 50-80% of males
      presenting with primary and secondary infertility, respectively. Factors
      contributing to the development and recurrence of varicocele include the
      abnormalities of the testicular venous drainage and outflow (varicose veins are
      more common on the left than on the right), the anatomical features of the veins
      of the testicular and prostatic venous plexus, the patients constitution,
      predisposition to constipation or diarrhea, physical activity. At present, the
      genetic defects, including the undifferentiated connective tissue dysplasia
      (UCTD) with hereditary insufficiency of venous valves and the weakness of the
      testicular vein walls, are thought to play a key role in the formation of a
      varicocele. Considering the importance of varicocele in the development of male
      infertility, the role of the UCTD in varicocele formation warrants a detailed
      investigation to provide an individual approach to patients and predict the
      disease recurrence.

PMID- 29634152
TI  - [Oxidative stress in some inflammatory and infectious urogenital diseases in
      men].
AB  - The article summarizes and analyzes the literature relating to lipid peroxidation
      and antioxidant protection in men with infectious and inflammatory diseases of
      diverse etiologies. These processes not only impair spermatogenesis, but also
      result in the oxidative stress in the blood and semen of men of reproductive age.
      Analysis of recent domestic and international literature suggests that oxidative
      stress is a key contributor and/or one of the pathogenetic links in the
      development of many infectious urogenital diseases in men.

PMID- 29634154
TI  - [Memorable dates and anniversaries in the history of urology and related
      specialities in 2018].

PMID- 29634153
TI  - [Dosage forms of sildenafil in the management of erectile dysfunction].
AB  - The experience in the management of erectile dysfunction shows that taking even
      the most effective medications in tablet form may be inconvenient due to the need
      for natural settings for intimacy. The phosphodiesterase type 5 inhibitor
      sildenafil, presented in the orally disintegrating film formulation (Dynamic
      Forward), differs from all forms of the drug for the treatment of erectile
      dysfunction available in the Russian pharmaceutical market. The drug in the form
      of a film makes it possible to realize a pathogenetic approach to treating ED
      without changing the patients habitual way of life.

PMID- 29634155
TI  - Use and misuse of mixed methods in population oral health research: A scoping
      review.
AB  - BACKGROUND: Despite the known benefits of a mixed methods approach in health
      research, little is known of its use in the field of population oral health.
      OBJECTIVE: To map the extent of literature using a mixed methods approach to
      examine population oral health outcomes. METHODS: For a comprehensive search of
      all the available literature published in the English language, databases
      including PubMed, Dentistry and Oral Sciences Source (DOSS), CINAHL, Web of
      Science and EMBASE (including Medline) were searched using a range of keywords
      from inception to October 2017. Only peer-reviewed, population-based studies of
      oral health outcomes conducted among non-institutionalised participants and using
      mixed methods were considered eligible for inclusion. RESULTS: Only nine studies
      met the inclusion criteria and were included in the review. The most frequent
      oral health outcome investigated was caries experience. However, most studies
      lacked a theoretical rationale or framework for using mixed methods, or
      supporting the use of qualitative data. Concurrent triangulation with a
      convergent design was the most commonly used mixed methods typology for
      integrating quantitative and qualitative data. The tools used to collect
      quantitative and qualitative data were mostly limited to surveys and interviews.
      CONCLUSION: With growing complexity recognised in the determinants of oral
      disease, future studies addressing population oral health outcomes are likely to
      benefit from the use of mixed methods. Explicit consideration of theoretical
      framework and methodology will strengthen those investigations.

PMID- 29634156
TI  - Morphology Controlling of ZnO Sub-Micron- and Micro-Structures from Sub-Micron
      Zinc Citrate Precursor.
AB  - A wet-chemical route has been demonstrated to investigate the morphology
      evolution of high crystalline ZnO sub-micron- and micro-structures created from a
      zinc citrate precursor consisted of zinc citrate nanoparticles. The
      concentrations of precursor zinc citrate and the addition of trisodium citrate
      were key factors in the controlling of ZnO micro-morphology. Assembled growth
      resulted in the formation of ZnO sub-micron- and micro-structure with twin-cone
      and flower-like morphologies. The ZnO flower was consisted of cone petals. The
      shape of ZnO microstructures was further adjusted using trisodium citrate to
      created thin and thick hexagonal-plates. In the case of a high Zn concentration,
      thick hexagonal-plates were split into a flower-like morphology. The
      investigation of morphological evolution indicated that trisodium citrate is
      critical to control the growth rate of polar (0001) plane. The formation of a
      flower-like structure is ascribed to the assembly of crystal units with a high
      zinc citrate concentration.

PMID- 29634157
TI  - PREVALENCE OF INTESTINAL PROTOZOAN INFECTIONS AMONG CHILDREN IN THAILAND: A LARGE
      SCALE SCREENING AND COMPARATIVE STUDY OF THREE STANDARD DETECTION METHODS.
AB  - A significant impact of intestinal parasitic infections on public healthhas
      mostly been neglected. Parasitic infections are one of risk factors for
      malnutritionin children. In this study, a large-scale screening of intestinal
      parasiticinfections among children in 16 schools in 6 regions of Thailand was
      performed.In addition, we compared sensitivity of methods currently employed for
      detectionof intestinal parasitic infection. Fecal samples collected from 1,909
      studentswere examined for intestinal parasites by simple smear, formalin-ethyl
      acetateconcentration (FECT), and Locke-egg-serum (LES) medium culture
      methods.Seven hundred and thirteen samples were infected with at least one
      intestinalparasite. The highest prevalence (82.8%) was found in Kanchanaburi
      Province,western Thailand. Blastocystis spp was the most common (32.8%) parasite,
      followedby Giardia duodenalis (4.2%), Ascaris lumbricoides (3.6%), hookworms
      (1.6%),Entamoeba histolytica (0.7%), Trichuris trichiura (0.5%), Enterobius
      vermicularis (0.5%),Strongyloides stercoralis (0.4%), minute intestinal flukes
      (0.2%), and Taenia spp(0.1%). Mixed parasitic infections were found in 121
      students. In a comparativestudy, we found that FECT was more sensitive (74.0%)
      than simple smear (55.0%)method for detecting helminths. However, sensitivity of
      these two methods is notsignificantly different for protozoan detection (31.2% by
      simple smear and 33.5%by FECT). LES culture technique was the most sensitive
      method (77.5%) for detectingBlastocystis spp. Our results indicate a high
      prevalence of intestinal parasiteinfection among Thai students. More sensitive
      methods should be developed fora large-scale screening of intestinal protozoan
      infection.

PMID- 29634158
TI  - Fabrication of Well-Ordered, Anodic Aluminum Oxide Membrane Using Hybrid
      Anodization.
AB  - Anodic Aluminum Oxide (AAO) is one of the most favorable candidates for
      fabrication of nano-meshed membrane for various applications due to its
      controllable pore size and self-ordered structure. The mechanism of AAO membrane
      is a simple and has been studied by many research groups, however the actual
      fabrication of membrane has several difficulties owing to its sensitivity of
      ordering, long anodizing time and unclearness of the pore. In this work, we have
      demonstrated enhanced process of fabrication symmetric AAO membrane by using
      "hybrid anodizing" (Hyb-A) method which include mild anodization (MA) followed by
      hard anodization (HA). This Hyb-A process can give highly ordered membrane with
      more vivid pore than two-step anodizing process. HA was implemented on the Al
      plate which has been already textured by MA for more ordered structure and HA
      plays a key role for formation of more obvious pore in Hyb-A. Our experimental
      results indicate that Hyb-A with proper process sequence would be one of the fast
      and useful fabrication methods for the AAO membrane.

PMID- 29634159
TI  - Application of the Synthesized Activated Carbon-4A Zeolite Composite from
      Elutrilithe in Wastewater Treatment.
AB  - The quartz abundant elutrilithe with several other elements from Pan zhihua, was
      taken as the main material to synthesize activated carbon-4A zeolite composite by
      hydrothermal crystallization after alkali fusion at 750  degrees C for 1 h under
      a flowing N2 atmosphere. Then the effect of alkali content and molar ratio of H2O
      versus Na2O on product was investigated, respectively. Finally, the activated
      carbon-4A zeolite composite was characterized by X-ray diffraction (XRD),
      scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT
      IR), thermogravimetry-differential scanning calorimetry (TG-DSC). The results
      showed that the crystallization product was activated carbon-4A zeolite composite
      with complete crystal form and the average particle size was about 1 MUm.
      Moreover, the composite materials had well adsorption capacities to water, hexane
      and metal ions such as Cu2+, Ni2+, Zn2+ and Pb2+ analyzing by inductively coupled
      plasma atomic emission spectrometry (ICP).

PMID- 29634160
TI  - OCCURRENCE AND GENETIC CHARACTERIZATION OF GRA6 AND SAG2 FROM TOXOPLASMA GONDII
      OOCYSTS IN CAT FECES, KUNMING, CHINA.
AB  - Toxoplasma gondii-like oocysts were detected in 4% of cat feces usinglight
      microscopy in Kunming, China. Amplicon was generated from these oocystsusing a T.
      gondii- but not Hammondia hammondi-specific primer set. Cat and KMmouse were
      susceptible to infection by these T. gondii-like oocysts. Tissue cystswere found
      in the brain of the experimentally infected animals and were infectiveto mouse,
      indicating that the T. gondii-like oocysts isolated from naturally infectedcats
      had a facultative secondary host life cycle. Comparison of GRA6 and SAG2sequences
      with those of reference strains indicated that the cat-derived T. gondii(KM
      isolate) were typical of T. gondii genotype II. This is the first report of
      isolation,identification, and genotyping of T. gondii from feline feces in China.
      Theoccurrence of oocyst shedding in the cat population studied was higher than
      thatfound in most cat populations world-wide, which strongly implies the need
      forfurther studies of population genetic structure of T. gondii, as well as for
      preventionand control of T. gondii infection in cats in China.

PMID- 29634161
TI  - FACTORS ASSOCIATED WITH THE PREVALENCE OF ASCARIS LUMBRICOIDES INFECTION AMONG
      PRESCHOOL CHILDREN IN A PLANTATIONCOMMUNITY, KANDY DISTRICT, SRI LANKA.
AB  - Plantation living conditions in Sri Lanka are often poor. Ascaris
      lumbricoidesinfections are common among those living in plantations. We conducted
      across sectional study of children aged 1 - 6 years living on a plantation to
      determinethe prevalence of ascariasis and factors associated with it in order to
      educate onprevention and to implement treatment programs. A total of 258
      preschool childrenselected using a simple random sampling was included in the
      study conductedduring January - April, 2013. Data regarding socio-demographic and
      hygienichabits were collected from heads of households via an interviewer
      administeredstructured questionnaire. Wet mount preparation, formaldehyde-ether
      sedimentationand Kato-Katz techniques were used to evaluate stool samples for
      Ascariseggs. The overall prevalence of Ascaris infection among study subjects was
      37.8%.On multivariate logistic regression analysis, factors significantly
      associated withAscaris infections were: living in attached houses (p=0.035),
      shared toilet facilities(p=0.001), de-worming period more than three months
      (p<0.001), maternal educationlevel (p<0.001) and living in the "Top" government
      administrative division(p=0.028) in the study area. Poor sanitation facilities
      and poor health educationwere important factors associated with Ascaris
      infections. A health educationprogram promoting improved sanitary facilities and
      good hygiene is needed toreduce the prevalence of Ascaris infection in the study
      population.

PMID- 29634162
TI  - EFFECTS OF SUGAR CONCENTRATION ON FECUNDITY, BITING BEHAVIOR AND SURVIVABILITY OF
      FEMALE AEDES (STEGOMYIA) ALBOPICTUS (SKUSE).
AB  - This study was conducted to better understand the effect of differentsucrose
      concentrations on Aedes albopictus fecundity, biting behavior and
      survival.Laboratory strain Ae. albopictus females were raised at four different
      sucroseconcentrations (10%, 30%, 50%, and 70%) and their fecundity, host biting
      on andsurvival rates were determined. Mosquitoes fed on high (50% or 70%)
      showedhigher mean fecundity rate compared to those on low (10% or 30%) sucrose
      concentration,and had higher daily biting rate. On the other hand, mosquitoes
      fedon the low (10% or 30%) sucrose concentrations recorded higher survival
      rate.These results suggest female mosquitoes deficient in nutrient intake during
      sugarfeeding may regain nutrients needed during blood feeding, whereas those
      fedon high sucrose concentration have high fecundity due to high biting rate
      buthave low survivability due to low sucrose intake during sugar feeding. Thus,
      Ae.albopictus females have a capability to regulate their metabolic needs based
      onsugar nutrient availability.

PMID- 29634163
TI  - Effects of Annealing Pressure on Microstructure and Conversion Efficiency for
      Electrodeposited CuInSe2 Absorbers.
AB  - As-deposited CuInSe2 thin films by electrodeposition method are usually
      accompanied with amorphous structure which is regarded detrimental for solar cell
      conversion efficiency. In this work, we proposed an annealing method under high
      pressure for improving the conversion efficiency of electrodeposited CuInSe2 thin
      film solar cells, and the microstructure of high-pressure annealed CuInSe2 films
      were also investigated. The annealing pressure was set from 100 kPa to 250 kPa,
      and the annealed CuInSe2 thin films were then fabricated into solar cell using
      standard process. Field-emission scanning electron microscopy (FESEM) images show
      that CuInSe2 films with higher annealing pressure demonstrate denser and smoother
      surface morphology. Results from X-ray diffraction (XRD) and Raman spectra
      indicate that annealing under high pressure enhanced the (1 1 2) preferential
      orientation of CuInSe2 films and also eliminated binary Cu-Se phases. Finally,
      through annealing CuInSe2 absorber layer under 200 kPa, the fill factor of the
      CuInSe2 solar cell was found to be improved from 28.4% to 55% and the efficiency
      from 2.77% to 6.91%.

PMID- 29634164
TI  - Conversion of Glycerol to Lactic Acid Catalyzed by Different-Sized Cu2O
      Nanoparticles in NaOH Aqueous Solution.
AB  - Different-sized Cu2O nanoparticles with the average particle sizes ranging from
      115 to 423 nm were prepared starting from CuSO4 using ascorbic acid as the
      reductant at room temperature. When Cu2O nanoparticles were used as the catalysts
      for hydrothermal conversion of glycerol at 230  degrees C in a NaOH aqueous
      solution, Cu2O nanoparticles effectively catalyzed the hydrothermal conversion of
      glycerol to lactic acid as compared to the conventional hydrothermal conversion
      of glycerol in a "pure" NaOH aqueous solution. Small-sized Cu2O nanoparticles
      showed higher catalytic activity than the large-sized ones. In a wide glycerol
      concentration range of 1-2.5 mol/L and a low mole ratio of Cu2O nanoparticle to
      glycerol of 2.5:100, the glycerol conversion and lactic acid selectivity were
      more than 86.2% and 87.2%, respectively, after reacting at 230  degrees C for 2
      h.

PMID- 29634165
TI  - Effect of Nanotube Morphologies on Multi-Walled Carbon Nanotubes Based Counter
      Electrode for Dye-Sensitized Solar Cell.
AB  - Multi-walled carbon nanotubes (MWCNTs) with different morphologies were
      introduced into dyesensitized solar cell (DSSC) as low-cost substitutes for Pt
      counter electrode (CE). The effect of length and orientation of MWCNTs on the
      power conversion efficiency (PCE) of DSSC with MWCNTs CE were studied by
      measuring electrochemical impedance spectroscopy of MWCNTs and the photocurrent
      density-voltage (J-V ) characteristics of DSSC in this study. Results revealed
      that the long MWCNTs showed better electrocatalytic activity of reducing
      triiodide ions than short MWCNTs and yielded the power conversion efficiency of
      2.42%. When the aligned multi-walled carbon nanotubes (AMWCNTs) with the same
      length as the long MWCNTs were used to prepare the CE, the power conversion
      efficiency of the DSSC reaches 2.95%. In order to further improve the performance
      of the DSSC, the processing of photoanode and counter electrode were adjusted.
      The power conversion efficiency of the cell with AMWCNTs as CE prepared by
      adjusted processing achieved 3.95% and the short circuit current density is
      superior to the DSSC with Pt as CEs, and it indicated the adjusted processing is
      beneficial to increase the overall performance of the dye-sensitized solar cell.

PMID- 29634166
TI  - Transition Metal (Fe, Co, Ni) Oxide Micro/Nanostructures: Phase, Morphology, and
      Decomposition of Precursors.
AB  - Transition metal oxides nano/micro structures including alpha-Fe2O3, Fe3O4, Co3O4
      and NiO were fabricated through controlling the decomposition of corresponding
      precursors. It is found that the morphology and phase composition of iron oxide
      depended strongly on heat-treatment approaches and conditions of the precursor.
      Furthermore, the iron oxide precursor created from FeCl2, FeCl3 and N2H4 in N,N
      dimethylformamide solution with polyvinyl pyrrolidone via a hydrothermal
      synthesis was an unknown phase according to the X-ray diffraction (XRD) data
      base. Fe3O4 nanoparticles (NPs) with several nanometers were obtained when the
      rod precursor was dissolved in water at room temperature, In contrast, when the
      precursor was calcined in an air atmosphere, porous alpha-Fe2O3 rods were
      acquired. Interestingly, the rod precursor can be transformed into perfect Fe3O4
      rhombic dodecahedrons in the case of keeping the solvothermal reaction for a long
      time. For comparison, cobalt and nickel oxide precursors were prepared. After
      calcination, porous rod-like Co3O4 crystals comprised of tiny particles and
      flower-like NiO hierarchical structures comprised of porous sheets were obtained.

PMID- 29634167
TI  - Simultaneous Extraction of DNA and RNA from Hepatocellular Carcinoma (Hep G2)
      Based on Silica-Coated Magnetic Nanoparticles.
AB  - Nucleic acid (NA) extraction from cancer cells is an essential step in molecular
      oncologic testing. The conventional NA extraction protocols, based on several
      ultracentrifugation steps, suffer from time-consuming and complex manipulation.
      Here, a magnetic nanoparticle (MNP) based method for simultaneous extraction of
      DNA and RNA from cancer cells is described. This MNP based technique has received
      great attention and significant interest due to its convenient manipulation, low
      cost and ease for automation. Different factors including lysis buffer, ethanol,
      MNPs and washing buffers which may affect the yield of nucleic acid were
      optimized. The average yield of DNA and RNA obtained from 1 mL Hep G2 (~106
      cells) ranged from 9.7 to 14.7 MUg with A260/A280 values between 1.68 and 2.01.
      The isolated DNA and RNA, using this method, were suitable for downstream
      activities such as PCR and RT-PCR.

PMID- 29634168
TI  - Photoluminescence Study of Ammonium-Free Chemical Bath Deposition of CdS
      Nanoparticles on Polyester Substrate.
AB  - Self-assembled cadmium sulfide (CdS) thin solid films were synthesized by
      chemical bath deposition (CBD) technique for different deposition times (20 min.
      24 h) on transparent and flexible polyester substrates using sodium acetate
      complex agent. CBD-CdS films were also deposited on glass (BK7) and quartz
      substrates, as reference. CBD-CdS films on polyester substrate showed a
      homogeneous deposition, reduction of chemical or structural defects (green
      emission), and large photoluminescence efficiency in comparison of CBD-CdS films
      deposited on Si-based substrates. Simulation of PL temperature dependence for
      polyester CdS films using the rate equation for the carrier population showed the
      presence of two decay pathways due to cadmium and sulphide defects at
      crystallite.

PMID- 29634169
TI  - Partial Delignification as Pretreatment for Nanoporous Carbon Material from
      Biomass.
AB  - For the pretreatment in order to nano prepare porous carbon from biomass such as
      bamboo, a mixture of acetic acid and hydrogen peroxide was used for the partial
      delignification of bamboo. The pretreatment should be effective for the removal
      of lignin because the lignin percentage after the pretreatment depended on the
      treatment time and the treatment temperature. For the concentration of the
      mixture used for the pretreatment in this study, a small amount of lignin (ca. 2
      wt%) remained even after a sufficiently-long treatment time. The BET specific
      surface area of the carbon material prepared by the heat treatment at 800 degrees
      C for 1 h under flowing N2 was related to the pretreatment conditions, and the
      specific surface areas of the samples were found to be related to the lignin
      percentage. The removal of lignin while maintaining the microstructure derived
      from plant tissue could be the reason for the local maximum of the specific
      surface area at ca. 5% of the lignin.

PMID- 29634175
TI  - PREVLENCE AND RISK FACTORS FOR OPISTHORCHIS VIVERRINI INFECTION AMONG CATS AND
      DOGS IN SIX DISTRICTS SURROUNDING THE UBOLRATANA DAM, AN ENDEMIC AREA FOR HUMAN
      OPISTHORCHIASIS IN NORTHEASTERN THAILAND.
AB  - Opisthorchis viverrini is a zoonotic liver fluke that causes opisthorchiasisamong
      humans in endemic areas, such as northeastern Thailand. The objectiveof this
      study was to determine the prevalence and risk factors for O. viverriniinfection
      among cats and dogs in six districts surrounding Ubolratana Dam. Fecalsamples of
      1,018 dogs and 249 cats were collected between 2008 and 2013 toexamine for O.
      viverrini infection using a modified formalin-ether concentrationtechnique. The
      prevalence of O. viverrini infection among cats (77 of 249, 30.92%)was higher
      than dogs (2 of 1,018, 0.20%). Age and the eating habits of cats wereassociated
      with O. viverrini infection. Cats aged >3 years were more likely thanthose aged
      <1 year [Odds ratio (OR)=2.96; 95% confidence interval (95% CI): 1.01-8.35; p =
      0.044] of being infected. Cats that consumed raw fish were significantlymore
      likely to be infected than those that consumed other foods (OR=1.82, 95%CI: 1.05
      3.16; p = 0.032). Cats had a higher prevalence of O. viverrini infection thandogs
      and may play an important role in the transmission and maintenance of thisdisease
      in the study area.

PMID- 29634176
TI  - Hybrid Biodegradable Hydrogels Obtained from Nanoclay and Carboxymethylcellulose
      Polysaccharide: Hydrophilic, Kinetic, Spectroscopic and Morphological Properties.
AB  - In this paper, series of novel nanocomposite hydrogels based on polyacrylamide
      (PAAm), carboxymethylcellulose (CMC) and nanoclay were synthesized. Hydrophilic,
      kinetic, spectroscopic and morphological properties were investigated as function
      of their constituents. Spectroscopic properties confirmed the obtaining of the
      nanocomposites. It was also observed that the nanocomposites have walls of pores
      with a more rugged morphology compared with the morphology of the hydrogel
      without clay, contributing to repel the water molecules. Besides, the results
      showed that the velocity and quantity of water uptake may be controlled by
      adjusting of matrix rigidity, i.e., nanoclay content into polymeric matrix. This
      behavior is required to future application in agriculture fields, specifically as
      carrier vehicle in controlled release of agrochemicals. Thus, these
      nanocomposites have technological application.

PMID- 29634177
TI  - ASSESSING THE COST BURDEN OF DENGUE INFECTION TO HOUSEHOLDS IN SEREMBAN,
      MALAYSIA.
AB  - Dengue is endemic in all parts of Malaysia. However, there is limiteddata
      regarding the cost burden of this disease at household level. We aimed toexamine
      the cost of dengue infection at the household level in Seremban
      District,Malaysia. This cost assessment can provide an insight to policy-makers
      abouteconomic impact of dengue infection in order to guide and prioritize control
      strategies.The data were collected via interview. We evaluated120 previous
      dengueinfection patients registered at the Tuanku Ja'afar Hospital, Seremban
      District,Malaysia. The average duration of dengue illness was 9.69 days. The
      averagehousehold days lost was 18.7; students lost an average of 6.3 days of
      school andpatients and caregivers lost an average of 12.5 days of work. The mean
      total costper case of dengue infection was estimated to be USD365.16 with the
      indirectcost being USD327.90 (89.8% of the total cost) and the direct cost being
      USD37.26(10.2% of the total cost). Our findings suggest each episode of dengue
      infectionimposes a significant financial burden at the household level in
      Seremban District,Malaysia; most of the burden being indirect cost. This cost
      needs to be factoredinto the overall cost to society of dengue infection. This
      data can inform policymakers when allocating resources to manage public health
      problems in Malaysia.

PMID- 29634178
TI  - Outstanding Elastic Limit of a Thin Film Composed of Nickel Nanosprings.
AB  - This paper presents experimental results of vertical loading using an atomic
      force microscope (AFM) performed on a thin film consisting of nickel helical
      nanoelements (nanosprings) formed by glancing angle deposition (GLAD) technique.
      As a helical element has large reversible deformation limit in general, a
      characteristic behavior is expected on the yielding of the film. From the load
      versus displacement curves, we find the outstanding elastic limit of nickel
      nanosprings film. The apparent yield strain is evaluated as epsilon' Y  = 5.2~6.2
      * 10-2, which is around 200 times of that in bulk nickel (epsilon Y  = 0.29~0.44
      * 10-3). However, comparing the maximum shear stress in the helical spring and
      the solid film, the shape effect (helical shape) is only around 10~20 times
      stemmed from the difference in the stress condition (torsion). The origin of
      difference is attributed to the size effect of nanosprings, as nano-scale metals
      have higher yield strain than that of bulk counterpart because of the difference
      in the understructure morphology. The combination of shape effect and size effect
      brings about the giant elastic limit on the film.

PMID- 29634179
TI  - Synthesis and Visible-Light Photocatalytic Activity of CeO2 Nanoboxes Based on
      Pearson's Principle.
AB  - The CeO2 nanoboxes with well-defined hollow structure were fabricated by template
      engaged coordinating etching of Cu2O cubes based on Pearson's hard and soft acid
      base principle. The morphologically uniform CeO2 nanoboxes have an average edge
      length of 400 nm and shell thickness of around 60 nm. The strong chemical
      affinity between Cu+ and S2O(2- 3) was the driving force for the etching of Cu2O
      templates and the formation of shells. A possible formation mechanism of CeO2
      nanoboxes was proposed. The synthesized CeO2 nanoboxes exhibit good
      photocatalytic activity for photodegradation of acid orange 7 (AO 7) under
      visible light irradiation.

PMID- 29634180
TI  - Thermal Treatment of Poly (N-vinylformamide) Produced Hydrogels Without the Use
      of Chemical Crosslinkers.
AB  - Hydrogel preparations using poly(N-vinylformamide) (PNVF) and poly(N
      vinylacetamide) (PNVA), which are composed of non-conjugated vinyl monomers, N
      vinylformamide (NVF) and N-vinylacetamide (NVA), were investigated without
      chemical crosslinkers. Hydrogen bonding interaction between the polymers and
      poly(ethylene glycol) have been firstly attempted to result in unstable film,
      which is easily soluble in water. On the other hand, the simple thermal treatment
      of the PNVF films at 200  degrees C for several hours produced the hydrogels
      after water immersion, although PNVA did not produce any hydrogels under the same
      condition. The swelling ratios of the formed hydrogel ranged from 100 to 250. The
      analysis of the supernatant reveals the structural change at alpha proton of
      PNVF. Furthermore, the decrease of molecular weights were observed by SEC
      analysis when the hydrogels formed. The possible mechanism of the crosslinking
      reaction is also discussed. The present study provides the novel method to
      prepare PNVF hydrogels without the use of chemical crosslinkers.

PMID- 29634181
TI  - Verification of Mechanism for the Formation of Carbon Nanotetrahedra Using
      Electron Beam Tomography.
AB  - When a carbon nanotube is flattened in two different directions, a
      nanotetrahedron is formed between the two nanoribbons. The distribution of the
      angles between the nanoribbons provides a clue to understanding the mechanism for
      the formation of nanotetrahedra. In this study, the angles between nanoribbons
      are measured using transmission electron microscopy-based electron beam
      tomography. The results are consistent with the proposed origami mechanism, in
      which the direction of flattening changes by approximately 90 degrees  during the
      growth of multi-walled carbon nanotubes.

PMID- 29634182
TI  - SALMONELLA SEPTIC BURSITIS OF THE ANKLE IN A HUMAN IMMUNODEFICIENCY VIRUS
      INFECTED PATIENT: A CASE REPORT AND LITERATURE REVIEW.
AB  - Salmonella is an unusual cause of septic bursitis of the ankle. A 48-yearoldmale
      fish-merchant with a history of HIV infection with a CD4 cell count of79 cells/ml
      presented with pain of the left ankle for 2 weeks and fever for 1 day.The bursal
      fluid was aspirated and culture of the fluid revealed Salmonella groupD. He was
      treated initially with intravenous ceftriaxone 2g once daily for 5 days,followed
      by oral ciprofloxacin 500mg twice daily for 4 weeks to give a treatmentcourse of
      5 weeks. Follow-up visit revealed complete recovery without any residualdefects.
      Salmonella should be considered in the differential of the etiologyof
      immunosuppressed patient with septic bursitis.

PMID- 29634183
TI  - Arsenic and Diabetes: Assessing Risk at Low-to-Moderate Exposures.

PMID- 29634184
TI  - WILLINGNESS TO PAY, QUALITY OF LIFE, AND KNOWLEDGE ON HERPES ZOSTER AMONG THAI
      PATIENTS PRIOR ZOSTER VACCINE ERA.
AB  - Herpes zoster is a devastating condition affecting patients' wellbeing.Policy on
      zoster vaccine in developing countries needs more data on the diseaseburden. This
      study was designed to assess willingness to pay, quality of life, andthe
      patients' knowledge on herpes zoster disease. All of the patients were askedto
      complete questionnaires about the willingness to pay for zoster treatment
      usingthe Dermatology Life Quality Index (DLQI) questionnaires in Thai version
      andbasic knowledge about herpes zoster. The demographic and clinical data were
      allrecorded. Eighty-two from one hundred and eighteen patients in this study
      werefemale (69.5%), and the mean (SD) age was 57.6 (14.9) years. The median of
      theirwillingness to pay for zoster treatment was THB500 (range of THB50-10,000)
      oronly 4.2% of median income per month. The mean of total DLQI score (SD) was10.7
      (6.2), which indicated moderate to severe impact on quality of life. Frommultiple
      linear regression analysis, three factors were related to inferior
      patients'quality of life including facial involvement (regression coefficients,
      b=4.789,p=0.001), presence of zoster complications (b=5.018, p=0.001) and
      advanced painscore (b=0.883, p<0.001). Moreover, more than half of them still had
      mistakenknowledge about the disease.

PMID- 29634185
TI  - TRENDS IN THE PREVALENCE OF SYPHILIS AMONG OLDER ADULTS IN SHANDONG, CHINA.
AB  - The epidemiology of syphilis among older adults in China has not beenwell
      studied. We studied changes over time in the prevalence of syphilis amongolder
      adults in Shandong, China to inform a syphilis intervention program inorder to
      develop management strategies. We retrospectively reviewed passivesurveillance
      data of syphilis among older adults in Shandong, China during2008-2013, reported
      by clinicians in medical facilities. The data included the stageof syphilis, age
      of patient and gender by year. The prevalences for first, second,latent and
      overall syphilis by age among adults aged >=60 years in Shandong were0.92, 0.70,
      2.37 and 3.92 cases per 100,000 population in 2008 and 2.66, 1.99, 9.11and 13.95
      cases per 100,000 population in 2013; giving average yearly increases of23.66%,
      23.24%, 30.90% and 28.90%, respectively. The reported overall prevalenceof
      syphilis among those aged >=80 years was greater than the general population(8.25
      vs 4.38 cases per 100,000 population in 2008; 21.99 vs 13.95 cases per
      100,000population in 2013). The prevalence of syphilis is increasing in the study
      population.Age appropriate interventions are needed to reduce the prevalence of
      syphilisin the study population.

PMID- 29634186
TI  - RISK FACTORS FOR LATENT TUBERCULOSIS INFECTION AMONG HEALTH-CARE WORKERS IN
      NORTHEASTERN THAILAND.
AB  - Health-care workers (HCWs) are a high-risk population for acquiringMycobacterium
      tuberculosis infection. Understanding the risk factors for latent
      tuberculosisinfection (LTBI) could provide information to facilitate an
      appropriatetuberculosis (TB) control program. We aimed to determine the
      prevalence of, andrisk factors for LTBI among HCWs in northeastern Thailand.
      Between 1 November2013 and 30 September 2015, we examined 112 HCWs at Srinagarind
      Hospital,Khon Kaen Province in northeastern Thailand using the QuantiFERON(r)
      TBGold In-Tube (QFT) assay. Twenty-one [18.8%; 95% confidence interval (CI): 11.5
      26.0%] HCWs had a positive QFT result - all of whom were determined to haveLTBI.
      The exposure risks and demographic data obtained from a questionnairewere
      compared between the 21 subjects who had a positive QFT assay and the91 subjects
      who had a negative QFT assay. Multivariate analysis showed factorssignificantly
      associated with a positive QFT assay were: age >=30 years (OR=18.88;95%CI: 1.52
      234.36), having worked as a nurse (OR=2.78; 95%CI: 1.19-6.49), havingbeen
      employed at that job for >=10 years (OR=8.78; 95%CI: 1.26-61.29) and havingbeen
      exposed to known TB patients (OR=13.32: 95%CI: 1.61-110.04).
      Appropriateguidelines need to be developed, especially for these at-risk workers
      to preventLTBI. These high-risk workers should also be considered for regular TB
      screening.

PMID- 29634187
TI  - Non-Conjugated Chitosan-Based Nanoparticles to Proteic Antigens Elicit Similar
      Humoral Immune Responses to Those Obtained with Alum.
AB  - Biodegradables Chitosan-based Nanoparticles (CS NPs) have been extensively
      studied as delivery system for therapeutic molecules and as efficient carriers or
      adjuvants in experimental vaccination. Physicochemical association between CS NPs
      and antigens is a key step for the biological function as carrier devices.
      However, for the adjuvant CS NPs property, it is not well known if coupling with
      vaccine antigens is required or not to potentiate the immune response. To address
      this issue, in this work, we evaluated the potential adjuvant effect of CS NPs by
      simply mixing with two different antigens such as Bovine Serum Albumin (BSA) or E
      protein from Dengue Virus serotype 2 (E protein DENV2). Thus the CS NPs were
      prepared by ionic gelation with sodium tripolyphosphate, resulting particles
      among 68 and 188 nm of size. Immunization of 6-8 week old female BALB/c mice,
      were carried out by intraperitoneal route with a simple combination of CS NPs
      either with BSA (CS NPs-BSA) at 10 MUg or with E protein DENV2 (CS NPs-Protein E)
      at 5 MUg. Combinations with the above antigens with CS NPs elicited robust
      specific primary and secondary humoral responses comparable to alum, a well-known
      adjuvant. BSA-specific IgG titers were detectable by day 14 after priming with
      the CS NPs-BSA formulation, with titers that ranged from 102 to 103 EU ml-. After
      a second immunization, the anti-BSA titers ranged around 104 EU ml-. In contrast,
      in the group of mice immunized with the protein alone, BSA-specific serum IgG
      titers were undetectable at day 14 and 28. For the immunizations with the CS NPs
      E protein formulation, we observed also a remarkable specific-antibody production
      in the primary response, with titers reaching 103 EU ml-. After the booster
      immunization the anti-E protein DENV2 antibodies titers reached peak values
      around 104 EU ml-. Interestingly, for both antigens, the combination with CS NPs
      polarized the immune response to a Th2-like profile, which is characterized
      mainly by the production of the IgG1 Isotype, confirming that CS NPs can enhance
      and modulate the humoral immune responses against different antigens
      independently of physicochemical conjugation. This could represent a
      simplification in the use of CS NPs as adjuvants in vaccination.

PMID- 29634188
TI  - TREATMENT OUTCOMES AMONG DIABETIC PATIENTS WITH TUBERCULOSIS IN THAILAND.
AB  - Tuberculosis (TB) is common in Thailand and the prevalence of diabetesmellitus
      (DM) is increasing. We conducted this study to determine the impactof DM on the
      outcome of pulmonary TB treatment in northern Thailand byretrospectively
      reviewing TB registry data. Data for all pulmonary TB patientsbeing treated at 95
      TB clinics in eight provinces from northern Thailand duringJanuary 2010-December
      2012 were retrospectively analyzed. TB treatment outcomeswere assessed by sputum
      tests at 2 months and 6 months after startingtreatment, and the overall success
      rate at the end of the treatment course wasdetermined. Factors associated with
      treatment outcome were evaluated. A totalof 7,807 new pulmonary TB patients were
      included in the analysis. Among those,555 (7%) had history of diabetes. At 2
      month after the intensive phase treatment,a negative sputum result was found in
      85% of all tested patients. The proportionof negative sputum at 2-month was
      similar in both TB with and without DM(85%). The overall treatment success rate
      was 77%. TB treatment outcomes werenot significantly different between TB
      patients with DM (84%) and without DM(77%). In conclusion, having DM did not
      affect the TB treatment outcome in thestudied population. More detailed studies
      of TB treatment outcome and level ofDM control are underway.

PMID- 29634189
TI  - CHARACTERIZATION OF CLOSTRIDIUM DIFFICILE ISOLATED FROM DIARRHEAL PATIENTS IN A
      TERTIARY-CARE HOSPITAL, KARNATAKA, SOUTH INDIA.
AB  - Increase in Clostridium difficile infection in tertiary-care hospitals in
      Karnataka,South India with a paucity of data on antibiotic susceptibility and
      geneticcharacteristics of the pathogen from this region of the country
      necessitated thisstudy. From April 2012 to December 2014, 480 hospitalized
      antibiotic-associateddiarrhea cases with a history of antibiotic treatment in the
      previous three weekswere enrolled. Sixteen percent of the samples were positive
      for C. difficile toxins Aand B by rapid enzyme immunoassay, anaerobic culture and
      multiplex PCR. In 40representative strains, minimum inhibitory concentrations
      (MICs) determined byE-test revealed that 39 strains were resistant to imipenem
      and moxifloxacin (MIC> 32 MUg/ml), 38 to clindamycin (MIC > 256 MUg/ml) and 19 to
      tetracycline (MIC > 4MUg/ml), while all 40 strains were susceptible to ampicillin
      (MIC < 2 MUg/ml), ampicillinsulbactam (MIC < 8 MUg/ml), metronidazole (MIC < 8
      MUg/ml) and vancomycingroup (MIC < 2 MUg/ml). Pulsed field gel-electrophoresis
      (PFGE) of 13 representativestrains grouped them into three clusters: cluster A
      consisting of two strains having> 65% similarity, cluster B of 6 strains with
      100% similarity (considered clonal) and3 strains with > 85% similarity, and
      cluster C of 2 strains with 50% similarity. ClustersA and C contained unrelated
      strains having different antibiograms. Periodicmonitoring of resistance profiles
      with epidemiological typing by PFGE should aidin interpretation of emerging drug
      resistant C. difficile clones.

PMID- 29634191
TI  - DETECTION OF HELICOBACTER PYLORI AND VIRULENCE-ASSOCIATED GENES IN SALIVA SAMPLES
      OF ASYMPTOMATIC PERSONS IN NORTHEAST THAILAND.
AB  - The aims of the study were to develop nested-PCR (targeting vacA andcagA), SYBR
      green quantitative PCR (targeting 16S rDNA) tests and comparedthem with indirect
      fluorescent-monoclonal antibody (IFA) method for determinationof the prevalence
      of Helicobacter pylori in 118 saliva samples from asymptomaticindividuals in Khon
      Kaen, Thailand. Detection limit of both PCR-based assayswas one cell. Prevalence
      of H. pylori in saliva samples was 55% based on the criterionof positivity of IFA
      test and one of the PCR-based methods or positivity ofboth PCR assays. Forty-nine
      percent of H. pylori detected carried cagA, encodinga cytotoxin associated with
      severe clinical outcomes. These results imply that themouth may be an important
      reservoir for H. pylori, with nearly 50% of the virulenttype that could possibly
      lead to gastroduodenal disease.

PMID- 29634190
TI  - MICROBIOLOGICAL SAFETY ASSESSMENT AND RISK MITIGATION OF INDIAN ROJAK (DEEP FRIED
      READYTO-EAT FOOD) IN SINGAPORE.
AB  - We conducted a microbiological assessment of Indian Rojak, a populardeep fried
      food in Singapore to evaluate its overall microbial quality, assess
      theeffectiveness of reheating and identify key food items that could contribute
      to themicrobial load of the dish. In 2009, an outbreak of foodborne illness
      associated withthis food led to 154 reported cases of acute gastroenteritis, 48
      were hospitalized and2 died. Vibrio parahaemolyticus was isolated from the
      patients. We evaluated 455Indian Rojak ingredients from 35 stalls; no Salmonella
      spp, Vibrio cholerae/parahaemolyticusor Escherichia coli O157:H7 were recovered
      from the studied samples. Thereheating by the food handlers significantly reduced
      the overall median StandardPlate Count (SPC) of food from 4.5 to 2.7 log colony
      forming units (CFU)/g (p<0.05).The cooked ingredients with the highest microbial
      loads were tofu and fish cake,with those purchased from wet markets having
      significantly higher bacterial loadsthan those purchased from supermarkets
      (p<0.05). The Rojak gravy had the lowestmedian bacterial load (1.9 log CFU/g).
      Raw, ready-to-eat vegetables, namely greenchillis, cucumbers and onions had
      higher levels ranging from 5.9 to 6.1 log CFU/g.Contamination with E. coli,
      Staphylococcus aureus, and Bacillus cereus was seen withsome of the ready-to-eat
      raw vegetables. Repeated education of food handlerswith emphasis on good hygiene
      practices should be conducted to reduce the riskof foodborne illnesses.

PMID- 29634192
TI  - MULTIDRUG RESISTANT AND EXTENDED SPECTRUM b-LACTAMASE PRODUCING SALMONELLA
      ENTERICA ISOLATED FROM FOOD ANIMALS IN PHATTHALUNG, THAILAND.
AB  - This study investigated antimicrobial resistance profiles and genes ofb-lactamase
      producing Salmonella enterica, isolates from animal feces and meatsamples at
      small-scale rural farms in Phatthalung Province, Thailand. Of 40 isolatesfrom
      swine feces 50%, 47%, 17%, 17%, and 15% were resistant to
      ampicillin,streptomycin, nalidixic acid, tetracycline, and chloramphenicol,
      respectively; of 29isolates from chicken feces 33%, 27%, 7%, and 3% were
      resistant to streptomycin,nalidixic acid, tetracycline, and ampicillin,
      respectively; and of 6 isolates from cattlefeces 67% were resistant to
      sulfamethoxazole and tetracycline, and 33% resistantto ampicillin, nalidixic acid
      and streptomycin. Of the 23 isolates from chickenmeat 96%, 96%, 78%, 73%, 61%,
      30%, and 9% were resistant to sulfamethoxazole,streptomycin, ampicillin,
      tetracycline, nalidixic acid, chloramphenicol, and ciprofloxacin,respectively;
      and of 31 isolates from pork meat 87%, 77%, 39%, 32%, 10%and 10% were resistant
      to sulfamethoxazole, tetracycline, streptomycin, ampicillin,nalidixic acid, and
      chloramphenicol, respectively. Three ampicillin-resistantisolates from swine
      feces carried the same extended-spectrum b-lactamase genebelonging to blaCTX-M
      group 1. The results of this study confirm the existence ofESBL in S. enterica
      isolated from food animals. Occurrence of an ESBL producingstrain of S. enterica
      constitutes a public health threat through transmission of thesestrains to humans
      via contaminated food or transfer of antimicrobial resistantgenes to human
      pathogens.

PMID- 29634193
TI  - MULTILOCUS SEQUENCE TYPING OF BRUCELLA ISOLATES FROM THAILAND.
AB  - Although brucellosis outbreaks in Thailand are rare, they cause abortionsand
      infertility in animals, resulting in significant economic loss. BecauseBrucella
      spp display > 90% DNA homology, multilocus sequence typing (MLST)was employed to
      categorize local Brucella isolates into sequence types (STs) and todetermine
      their genetic relatedness. Brucella samples were isolated from vaginalsecretion
      of cows and goats, and from blood cultures of infected individuals.
      Brucellaspecies were determined by multiplex PCR of eight loci, in addition to
      MLSTbased on partial DNA sequences of nine house-keeping genes. MLST analysisof
      36 isolates revealed 78 distinct novel allele types and 34 novel STs, while
      twoisolates possessed the known ST8. Sequence alignments identified
      polymorphicsites in each allele, ranging from 2-6%, while overall genetic
      diversity was 3.6%.MLST analysis of the 36 Brucella isolates classified them into
      three species, namely,B. melitensis, B. abortus and B. suis, in agreement with
      multiplex PCR results. Geneticrelatedness among ST members of B. melitensis and
      B. abortus determinedby eBURST program revealed ST2 as founder of B. abortus
      isolates and ST8 thefounder of B. melitensis isolates. ST 36, 41 and 50 of Thai
      Brucella isolates wereidentified as single locus variants of clonal cluster (CC)
      8, while the majority ofSTs were diverse. The genetic diversity and relatedness
      identified using MLSTrevealed hitherto unexpected diversity among Thai Brucella
      isolates. Geneticclassification of isolates could reveal the route of brucellosis
      transmission amonghumans and farm animals and also reveal their relationship with
      other isolatesin the region and other parts of the world.

PMID- 29634194
TI  - DEVELOPMENT OF AN ANTIBIOTIC OPTIONS INDEX FOR ANTIBIOTIC RESISTANCE MONITORING.
AB  - Using antibiogram data to indicate the overall antibiotic resistance ofa pathogen
      is complicated by the multiple antibiotic susceptibilities reported inthe
      antibiogram. The objectives of this study were to develop and determine
      thebenefits of an Antibiotic Options Index (AOI); an index that summarizes
      antibioticsusceptibility data for a pathogen by presenting it as the availability
      of antibiotictreatment options. The AOI was calculated using antibiogram data for
      the sevenmost commonly isolated pathogens from the National Antimicrobial
      ResistanceSurveillance Center of Thailand between 1998 and 2014 and was
      classified asacceptable (AOI >= 0.8) or unacceptable (AOI < 0.8) based on the
      availability oftreatment options. The AOI identified two problematic pathogens:
      Acinetobacterbaumannii and methicillin-resistant Staphylococcus aureus (MRSA).
      For A. baumannii,the probability of having at least two viable antibiotic
      treatment options (AOIm2)decreased from an acceptable level (0.93) in 1998 to an
      unacceptable level (0.53)in 2014 and for MRSA the AOIm2 decreased from an
      acceptable level (0.82) in 1998to an unacceptable level (0.47) in 2014. By
      including the idea that the problemwith increasing antibiotic resistance is a
      problem with treating infections, the AOIeffectively compiles susceptibility data
      to present it as the probability of havingeffective antibiotic treatment. This
      index is calculated from widely available antibiogramdata, making it more
      suitable to be used to monitor antibiotic resistanceat the hospital, provincial
      and national levels.

PMID- 29634195
TI  - ANEMIA AMONG LACTATING MOTHERS IN KOKANG, MYANMAR.
AB  - Anemia is an important public health problem among lactating mothersin the
      developing countries. The aim of the study was to determine the prevalenceof
      anemia in lactating mothers in Kokang, Myanmar and its associated riskfactors. We
      conducted a cross sectional study of 65 lactating mothers duringJune-October
      2014. Each participant filled out a questionnaire asking about diet,source of
      drinking water, health status, socioeconomic and demographic factors.Each
      participant was also evaluated anthropometrically and had blood taken todetermine
      their hemoglobin and their iron, copper, zinc, calcium, and magnesiumlevels. The
      prevalence rate of anemia (hemoglobin 81-120 g/l) in study subjects was73.8%, and
      10.8% had severe anemia (hemoglobin <= 80 g/l). Factors of malnutrition(mid-upper
      arm circumference < 23.5 cm, p = 0.013), iron deficiency (serum ironconcentration
      < 6.6 mmol/l, p = 0.008), and source of drinking water (p = 0.031)were related to
      anemia. Fifty-six point three percent of women with anemia hada low serum iron
      level. Anemia was common among study subjects in Kokang.Since a large portion of
      women in our study with anemia had a low serum ironlevel, we conclude the major
      cause of anemia in our study was iron deficiency.

PMID- 29634196
TI  - ADIPOQ POLYMORPHISMS AMONG THAIS WITH PRE-DIABETES.
AB  - Studies have shown that polymorphisms of adiponectin gene (ADIPOQ)are associated
      with risk of developing type 2 diabetes mellitus (T2DM).However, no studies have
      investigated the association between genetic variantsof ADIPOQ and pre-diabetes,
      a group at higher risk for developing T2DM. Atotal of 75 pre-diabetes and 130
      normal subjects were recruited from volunteersin Bangkok, Thailand. Individuals
      with pre-diabetes were selected based onAmerican Diabetes Association diagnostic
      criteria. Six ADIPOQ polymorphismswere genotyped using polymerase chain reaction
      restriction fragment lengthpolymorphism technique. ADIPOQ polymorphism rs266729
      C>G is significantlyassociated with pre-diabetes (p = 0.006). CG/GG genotypes
      were found among 60%and 40% of pre-diabetes and normal subjects, respectively.
      SNP rs266729 C>G wasassociated with increased pre-diabetes risk (OR = 2.64; 95%
      CI: 1.18-5.89, p = 0.018).No significant differences were found between pre
      diabetes and normal subjectsfor other ADIPOQ polymorphisms. However, haplotype
      analysis revealed thathaplotype GGTAAT is significantly associated with pre
      diabetes when comparedwith GCGAAC reference haplotype (OR = 22.31; 95% CI: 1.37
      361.93, p = 0.03).Our data indicate that ADIPOQ rs266729 C>G polymorphism may
      contribute tothe genetic risk of pre-diabetes and provide preliminary data useful
      in geneticscreening for pre-diabetes among Thais.

PMID- 29634197
TI  - ASSOCIATION OF ENVIRONMENTAL FACTORS AND ADIPOSITY IN THAI SCHOOL CHILDREN: A
      STRUCTURAL EQUATION MODELING APPROACH.
AB  - This study used structural equation modeling (SEM) to examine associationsbetween
      environmental factors and indicators of adiposity. We analyzed datafrom a cross
      sectional Southeast Asian Nutritional Survey of 1,161 Thai childrenaged 7.0-12.9
      years who were recruited by multi-stage sampling. Standardizedquestionnaires
      provided data on socio-economic, health status, and physical activity,while a 24
      hour dietary recall provided dietary intake data. SEM analysisshow that socio
      economic, health status, physical activity, and nutrient intake werenot
      associated directly with adiposity, but their relationship with adiposity wasvia
      the environment. This analysis confirms many relationships between possiblecausal
      factors and adiposity, and it enables insight into the complex mechanismsleading
      to higher body fat. As such, it could serve as a working model to combatthe
      increasing prevalence of obesity (excess body fat) affecting many countries.

PMID- 29634198
TI  - CHILDREN'S EATING BEHAVIOR QUESTIONNAIRE: FACTORIAL VALIDATION AND DIFFERENCES IN
      SEX AND EDUCATIONAL LEVEL IN THAI SCHOOL-AGE CHILDREN.
AB  - The purposes of this study were to test the validity of the Thai
      versionChildren's Eating Behavior Questionnaire (CEBQ) and to describe the
      variationin eating style among school-age children. This school-based, cross
      sectionalstudy was conducted in five primary public schools selected from Bangkok
      andthe three regions of Thailand (North, Northeast, South). Six hundred and
      eightystudents from the first and fourth grade classes were included in our
      study. TheCEBQ was used to assess the eating styles among these children. Factor
      analysisrevealed an eight-factor solution accounted for 57.1% of the total
      variance. Mostof the scale items loaded as expected and their factor loadings
      were comparable tothose obtained from the original study in England. The
      reliability coefficients areall within acceptable ranges (more than 0.7), with
      the exceptions of the subscalesof 'slowness in eating' and 'emotional under
      eating' with the coefficients of 0.64and 0.69, respectively. There were some
      significant differences in eating behaviorsbetween sex and educational level.
      Boys scored higher on 'enjoyment of food'compared with girls (p<0.05), as well as
      on 'desire to drink' (p<0.05). Childrenin Grade 1 scored higher on 'satiety
      responsiveness' (p<0.001) and 'slowness ineating' (p<0.001) compared with those
      in Grade 4. This study supported the useof CEBQ as an appropriate tool for
      measuring the eating behaviors among Thaischool-age children.

PMID- 29634199
TI  - PREVALENCE AND RISK FACTORS FOR CARDIAC IRON OVERLOAD AND CARDIOVASCULAR
      COMPLICATIONS AMONG PATIENTS WITH THALASSEMIA IN NORTHERN THAILAND.
AB  - Cardiovascular complications are the most common cause of deathamong thalassemia
      patients in Thailand. In this study, we evaluated the prevalenceof cardiac iron
      overload, cardiovascular complications and the associatedrisk factors. The
      information obtained will serve as a guidance for surveillance,prevention and
      early treatment of the complications. We conducted a cross sectionalstudy of Thai
      patients with thalassemia attending Chiang Mai UniversityHospital, Thailand.
      Cardiac T2* magnetic resonance imaging (CMR T2*) was usedto evaluate the
      myocardial iron deposition and echocardiography was used toevaluate the cardiac
      function and to identify pulmonary hypertension. Ninety-onepatients were included
      in the study; 64% females with a median age of 31 (16-75)years. Of the total
      study subjects, 49% had homozygous beta thalassemia, 32% hadbeta thalassemia/Hb E
      disease, and 19% had Hb H disease. Half the participantswere transfusion
      dependent and 84% had received iron chelation. The CMR T2*showed cardiac iron
      overload in 10 patients (11%). The maximum ferritin levelin the previous 3 years
      was higher among the patients with cardiac iron overload(6,310 ng/ml) than among
      the patients without cardiac iron overload (3,352 ng/ml)(p=0.001). Twenty-one
      patients (23%) had cardiovascular complications. Cardiomyopathywas seen in 8% of
      patients [17% in patients with transfusion-dependentthalassemia (TDT) and none in
      patients with non-transfusion-dependent thalassemia(NTDT)] and pulmonary
      hypertension in 15% of patients (14% in patientswith TDT and 16% in patients with
      NTDT). TDT and cardiac iron overload weresignificantly associated with
      cardiomyopathy. No risk factors were found to be significantlyassociated with
      pulmonary hypertension. In summary, cardiac iron overloadand cardiomyopathy are
      important complications in TDT while pulmonaryhypertension is seen in both TDT
      and NTDT. Iron chelation and monitoring ofserum ferritin level will prevent
      cardiac iron overload and cardiomyopathy. Intervalmonitoring with
      echocardiography will help with early identification ofthe cardiac complications.

PMID- 29634200
TI  - BURNOUT AND OCCUPATIONAL PARTICIPATIONAMONG TURKISH DENTAL STUDENTS.
AB  - The aim of the present study was to investigate the prevalence ofburnout and
      occupational participation limitation among dental students in adental school in
      Turkey. Four hundred fifty-eight dental students (females=153;males=305) were
      included in the study. The age range varied from 17-to-38years. Maslach Burnout
      Inventory-Student Version (MBI-SV) and Canadian OccupationalPerformance Measure
      (COPM) were used to gather data. Descriptiveanalyses, t-test, and Kruskall-Wallis
      test for independent groups were used fordata analyses. The results indicated
      that 26% of all the students have burnoutin terms of emotional exhaustion (25%),
      cynicism (18%), and academic efficacy(14%). The results showed that burnout is
      statistically significant in relation todemographics (p<0.05). Twenty-four
      percent of the students showed considerablydecreased occupational performance and
      satisfaction scores, which suggestedoccupational participation limitations.
      Occupational performance and satisfactionscores were inversely correlated with
      emotional exhaustion and cynicism,while directly correlated with reduced academic
      efficacy (p<0.05). The results ofthe present study indicates that burnout and
      occupational participation limitationcan be seen among dental students. Students
      with burnout may also haveoccupational participation limitation. Enriching dental
      education programs withdifferent psychological strategies may be useful for
      education of healthy dentistsand improve the quality of oral and dental health
      services.

PMID- 29634201
TI  - PERSONAL AND INTERPERSONAL FACTORS RELATED TO SUICIDAL IDEATION AMONG RURAL
      VIETNAMESE ADOLESCENTS.
AB  - The purpose of this study was to explore the level of suicidal ideationand its
      personal, peer- and family-related factors among rural Vietnamese adolescents.A
      self-administered survey was conducted with 171 students from twomiddle schools
      in two communes of Quang-Tri Province in Vietnam. Suicidalideation and risk
      factors were measured using the Vietnamese version of theWorld Health
      Organization (WHO) Global School-based Student Health Survey(GSHS). The data were
      analyzed by chi-square test and logistic regression analysis.The prevalence of
      suicidal ideation was 14.2%, and no gender differences werefound. The major risk
      factors associated with suicidal ideation were feelings ofloneliness, having no
      close friends, and parental drinking. The findings suggestthat student
      interpersonal skills, and family and community involvement arekey considerations
      for the development of a suicide prevention program for thispopulation. Further
      research is suggested to develop and evaluate a school-basedculturally adaptive
      suicide prevention program.

PMID- 29634231
TI  - All-Electronic Quantification of Neuropeptide-Receptor Interaction Using a Bias
      Free Functionalized Graphene Microelectrode.
AB  - Opioid neuropeptides play a significant role in pain perception, appetite
      regulation, sleep, memory, and learning. Advances in understanding of opioid
      peptide physiology are held back by the lack of methodologies for real-time
      quantification of affinities and kinetics of the opioid neuropeptide-receptor
      interaction at levels typical of endogenous secretion (<50 pM) in biosolutions
      with physiological ionic strength. To address this challenge, we developed all
      electronic opioid-neuropeptide biosensors based on graphene microelectrodes
      functionalized with a computationally redesigned water-soluble MU-opioid
      receptor. We used the functionalized microelectrode in a bias-free charge
      measurement configuration to measure the binding kinetics and equilibrium binding
      properties of the engineered receptor with [d-Ala2, N-MePhe4, Gly-ol]-enkephalin
      and beta-endorphin at picomolar levels in real time.

PMID- 29634232
TI  - Self-Assembly of Ionic Microgels Driven by an Alternating Electric Field: Theory,
      Simulations, and Experiments.
AB  - The structural properties of a system of ionic microgels under the influence of
      an alternating electric field are investigated both theoretically and
      experimentally. This combined investigation aims to shed light on the structural
      transitions that can be induced by changing either the driving frequency or the
      strength of the applied field, which range from string-like formation along the
      field to crystal-like structures across the orthogonal plane. In order to
      highlight the physical mechanisms responsible for the observed particle self
      assembly, we develop a coarse-grained description, in which effective
      interactions among the charged microgels are induced by both equilibrium ionic
      distributions and their time-averaged hydrodynamic responses to the applied
      field. These contributions are modeled by the buildup of an effective dipole
      moment at the microgels backbones, which is partially screened by their ionic
      double layer. We show that this description is able to capture the structural
      properties of this system, allowing for very good agreement with the experimental
      results. The model coarse-graining parameters are indirectly obtained via the
      measured pair distribution functions and then further assigned with a clear
      physical interpretation, allowing us to highlight the main physical mechanisms
      accounting for the observed self-assembly behavior.

PMID- 29634233
TI  - Role of BRCA1 in Neuronal Death in Alzheimer's Disease.
AB  - Oxidative damage of DNA has recently been indicated as one of the strong
      pathogenic agent in Alzheimer's disease (AD). Oxidative stress induces numerous
      signaling pathways, including DNA damage response (DDR), associated with the
      breast cancer type 1 susceptibility protein (BRCA1) protein, known to date from
      numerous reports in the cancer field. In this Viewpoint, we discuss the latest
      discoveries related to the role of BRCA1 in the death of neurons in AD. We
      underline the role of BRCA1 in the development of neurons and speculate on the
      consequences of BRCA1 dysfunction in the dying brain. In general, this Viewpoint
      is in a line with several recent reports on the processes and players common at
      the molecular and genetic level for neurodegenerative and cancerous diseases.

PMID- 29634234
TI  - Metal-Embedded Porous Graphitic Carbon Fibers Fabricated from Bamboo Sticks as a
      Novel Cathode for Lithium-Sulfur Batteries.
AB  - Lithium-sulfur batteries (LSBs) are deemed to be among the most prospective next
      generation advanced high-energy batteries. Advanced cathode materials fabricated
      from biological carbon are becoming more popular due to their unique properties.
      Inspired by the fibrous structure of bamboo, herein we put forward a smart
      strategy to convert bamboo sticks for barbecue into uniform bamboo carbon fibers
      (BCF) via a simple hydrothermal treatment proceeded in alkaline solution. Then
      NiCl2 is used to etch the fibers through a heat treatment to achieve Ni-embedded
      porous graphitic carbon fibers (PGCF/Ni) for LSBs. The designed PGCF/Ni/S
      electrode exhibits improved electrochemical performances including high initial
      capacity (1198 mAh g-1 at 0.2 C), prolonged cycling life (1030 mAh g-1 at 0.2 C
      after 200 cycles), and improved rate capability. The excellent properties are
      attributed to the synergistic effect of 3D porous graphitic carbon fibers with
      highly conductive Ni nanoparticles embedded.

PMID- 29634235
TI  - Fenobody: A Ferritin-Displayed Nanobody with High Apparent Affinity and Half-Life
      Extension.
AB  - Nanobodies consist of a single domain variable fragment of a camelid heavy-chain
      antibody. Nanobodies have potential applications in biomedical fields because of
      their simple production procedures and low cost. Occasionally, nanobody clones of
      interest exhibit low affinities for their target antigens, which, together with
      their short half-life limit bioanalytical or therapeutic applications. Here, we
      developed a novel platform we named fenobody, in which a nanobody developed
      against H5N1 virus is displayed on the surface of ferritin in the form of a
      24mer. We constructed a fenobody by substituting the fifth helix of ferritin with
      the nanobody. TEM analysis showed that nanobodies were displayed on the surface
      of ferritin in the form of 6 * 4 bundles, and that these clustered nanobodies are
      flexible for antigen binding in spatial structure. Comparing fenobodies with
      conventional nanobodies currently used revealed that the antigen binding apparent
      affinity of anti-H5N1 fenobody was dramatically increased (~360-fold). Crucially,
      their half-life extension in a murine model was 10-fold longer than anti-H5N1
      nanobody. In addition, we found that our fenobodies are highly expressed in
      Escherichia coli, and are both soluble and thermo-stable nanocages that self
      assemble as 24-polymers. In conclusion, our results demonstrate that fenobodies
      have unique advantages over currently available systems for apparent affinity
      enhancement and half-life extension of nanobodies. Our fenobody system presents a
      suitable platform for various large-scale biotechnological processes and should
      greatly facilitate the application of nanobody technology in these areas.

PMID- 29634236
TI  - Selective Transformation of CO2 to CO at a Single Nickel Center.
AB  - Carbon dioxide conversion mediated by transition metal complexes continues to
      attract much attention because of its future potential utilization as a nontoxic
      and inexpensive C1 source for the chemical industry. Given the presence of nickel
      in natural systems that allow for extremely efficient catalysis, albeit in an Fe
      cluster arrangement, studies that focus on selective CO2 conversion with
      synthetic nickel species are currently of considerable interest in our group. In
      this Account, the selective conversion of CO2 to carbon monoxide occurring at a
      single nickel center is discussed. The chemistry is based on a series of related
      nickel pincer complexes with attention to the uniqueness of the coordination
      geometry, which is crucial in allowing for particular reactivity toward CO2. Our
      research is inspired by the efficient enzymatic CO2 catalysis occurring at the
      active site of carbon monoxide dehydrogenase. Since the binding and reactivity
      toward CO2 are controlled in part by the geometry of a L3Ni scaffold, we have
      explored the chemistry of low-valent nickel supported by PPMeP and PNP ligands,
      in which a pseudotetrahedral or square-planar geometry is accommodated. Two
      isolated nickel-CO2 adducts, (PPMeP)Ni(eta2-CO2-kappa C) (2) and {Na(12-C
      4)2}{(PNP)Ni(eta1-CO2-kappa C)} (7), clearly demonstrate that the geometry of the
      nickel ion is crucial in the binding of CO2 and its level of activation. In the
      case of a square-planar nickel center supported by a PNP ligand, a series of
      bimetallic metallacarboxylate Ni-MU-CO2-kappa C, O-M species (M = H, Na, Ni, Fe)
      were synthesized, and their structural features and reactivity were studied.
      Protonation cleaves the C-O bond, resulting in the formation of a nickel(II)
      monocarbonyl complex. By sequential reduction, the corresponding mono- and zero
      valent Ni-CO species were produced. The reactivities of three nickel carbonyl
      species toward various iodoalkanes and CO2 were explored to address whether their
      corresponding reactivities could be controlled by the number of valence d
      electrons. In particular, a (PNP)Ni(0)-CO species (13) shows immediate reactivity
      toward CO2 but displays multiple product formation. By incorporation of a -CMe2-
      bridging unit, a structurally rigidified acriPNP ligand was newly designed and
      produced. This ligand modification was successful in preparing the T-shaped
      nickel(I) metalloradical species 9 exhibiting open-shell reactivity due to the
      sterically exposed nickel center possessing a half-filled d x2- y2 orbital. More
      importantly, the selective addition of CO2 to a nickel(0)-CO species was enabled
      to afford a nickel(II)-carboxylate species (22) with the expulsion of CO(g).
      Finally, the (acriPNP)Ni system provides a synthetic cycle in the study of the
      selective conversion of CO2 to CO that involves two-electron reduction of Ni-CO
      followed by the direct addition of CO2 to release the coordinated CO ligand.

PMID- 29634237
TI  - High GC Content Cas9-Mediated Genome-Editing and Biosynthetic Gene Cluster
      Activation in Saccharopolyspora erythraea.
AB  - The overexpression of bacterial secondary metabolite biosynthetic enzymes is the
      basis for industrial overproducing strains. Genome editing tools can be used to
      further improve gene expression and yield. Saccharopolyspora erythraea produces
      erythromycin, which has extensive clinical applications. In this study, the
      CRISPR-Cas9 system was used to edit genes in the S. erythraea genome. A
      temperature-sensitive plasmid containing the PermE promoter, to drive Cas9
      expression, and the Pj23119 and PkasO promoters, to drive sgRNAs, was designed.
      Erythromycin esterase, encoded by S. erythraea SACE_1765, inactivates
      erythromycin by hydrolyzing the macrolactone ring. Sequencing and qRT-PCR
      confirmed that reporter genes were successfully inserted into the SACE_1765 gene.
      Deletion of SACE_1765 in a high-producing strain resulted in a 12.7% increase in
      erythromycin levels. Subsequent PermE- egfp knock-in at the SACE_0712 locus
      resulted in an 80.3% increase in erythromycin production compared with that of
      wild type. Further investigation showed that PermE promoter knock-in activated
      the erythromycin biosynthetic gene clusters at the SACE_0712 locus. Additionally,
      deletion of indA (SACE_1229) using dual sgRNA targeting without markers increased
      the editing efficiency to 65%. In summary, we have successfully applied Cas9
      based genome editing to a bacterial strain, S. erythraea, with a high GC content.
      This system has potential application for both genome-editing and biosynthetic
      gene cluster activation in Actinobacteria.

PMID- 29634238
TI  - Synthesis and Electrochemical Properties of LiNi0.5Mn1.5O4 for Li-Ion Batteries
      by the Metal-Organic Framework Method.
AB  - A LiNi0.5Mn1.5O4 cathode material with high surface orientation was prepared via
      a complexing reaction coupled with the elevated-temperature solid-state method.
      First, a bimetal-organic framework containing Ni2+ and Mn2+ ions was synthesized
      via a self-assembly route using pyromellitic acid (PMA) as a dispersant and
      complexing agent. This step was followed by calcination with lithium acetate
      using PMA as a structure-directing agent. The resulting LiNi0.5Mn1.5O4 (M-LNMO)
      cathode material was investigated using X-ray diffraction, transmission and
      scanning electron microscopies, X-ray photoelectron spectroscopy, energy
      dispersive X-ray spectroscopy, cyclic voltammetry, electrochemical impedance
      spectroscopy, and charge/discharge tests. For comparison, LiNi0.5Mn1.5O4 samples
      were prepared by coprecipitation and the solid-phase method under the same
      conditions. M-LNMO was highly crystalline with low impurity, uniform grain size,
      and a preferred orientation in the (111) and (110) planes. Owing to these
      advantages, the M-LNMO cathode material exhibited overwhelmingly high cyclic
      stability and rate capability and M-LNMO delivered a capacity of 145 mAh g-1 at a
      discharge rate of 0.1C and a discharge capacity retention of 86.6% at 5C after
      1000 cycles. Even at an extremely high discharge rate (10C), the specific
      capacity was 112.7 mAh g-1, and 78.7% of its initial capacity was retained over
      500 cycles. The superior electrochemical performance, particularly during a low
      rate operation, was conferred by improved crystallinity and the crystal
      orientation of the particles.

PMID- 29634239
TI  - Time-Dependent Alterations in the Expression of NMDA Receptor Subunits along the
      Dorsoventral Hippocampal Axis in an Animal Model of Nascent Psychosis.
AB  - Psychosis is a mental condition that is characterized by hallucinations,
      delusions, disordered thought, as well as socio-emotional and cognitive
      impairments. Once developed, it tends to progress into a chronic psychotic
      illness. Here, the duration of untreated psychosis plays a crucial role: the
      earlier the treatment begins, relative to the first episode of the disease, the
      better the patient's functional prognosis. To what extent the success of early
      interventions relate to progressive changes at the neurotransmitter receptor
      level is as yet unclear. In fact, very little is known as to how molecular
      changes develop, transform, and become established following the first psychotic
      event. One neurotransmitter receptor for which a specific role in psychosis has
      been discussed is the N-methyl-d-aspartate receptor (NMDAR). This receptor is
      especially important for information encoding in the hippocampus. The hippocampus
      is one of the loci of functional change in psychosis, to which a role in the
      pathophysiology of psychosis has been ascribed. Here, we examined whether changes
      in NMDAR subunit expression occur along the dorsoventral axis of the hippocampus
      1 week and 3 months after systemic treatment with an NMDAR antagonist (MK801)
      that initiates a psychosis-like state in adult rats. We found early (1 week)
      upregulation of the GluN2B levels in the dorso-intermediate hippocampus and late
      (3 month) downregulation of GluN2A expression across the entire CA1 region. The
      ventral hippocampus did not exhibit subunit expression changes. These data
      suggest that a differing vulnerability of the hippocampal longitudinal axis may
      occur in response to MK801-treatment and provide a time-resolved view of the
      putative development of pathological changes of NMDAR subunit expression in the
      hippocampus that initiate with an emulated first episode and progress through to
      the chronic stabilization of a psychosis-like state in rodents.

PMID- 29634240
TI  - Size-Modulable Nanoprobe for High-Performance Ultrasound Imaging and Drug
      Delivery against Cancer.
AB  - Among medical imaging modalities available in the clinic, ultrasonography is the
      most convenient, inexpensive, ionizing-radiation-free, and most common.
      Micrometer-size perfluorocarbon bubbles have been used as efficient contrast for
      intravascular ultrasonography, but they are too big for tumor penetration.
      Nanodroplets (250-1000 nm) encapsulating both perfluorocarbon and drug have been
      used as an ultrasound-triggered release drug delivery platform against cancer,
      but they are generally not useful as a tumor imaging agent. The present study
      aims to develop a type of pH-sensitive, polymersome-based, perfluorocarbon
      encapsulated ultrasonographic nanoprobe, capable of maintaining at 178 nm during
      circulation and increasing to 437 nm at the acidic tumor microenvironment. Its
      small size allowed efficient tumor uptake. At the tumor site, the nanoparticle
      swells, resulting in lowering of the vaporization threshold for the
      perfluorocarbon, efficient conversion of nanoprobes to echogenic
      nano/microbubbles for ultrasonic imaging, and eventual release of doxorubicin
      from the theranostic nanoprobe for deep tissue chemotherapy, triggered by
      irradiation with low-frequency ultrasound.

PMID- 29634242
TI  - A Green-Light-Responsive System for the Control of Transgene Expression in
      Mammalian and Plant Cells.
AB  - The ever-increasing complexity of synthetic gene networks and applications of
      synthetic biology requires precise and orthogonal gene expression systems. Of
      particular interest are systems responsive to light as they enable the control of
      gene expression dynamics with unprecedented resolution in space and time. While
      broadly used in mammalian backgrounds, however, optogenetic approaches in plant
      cells are still limited due to interference of the activating light with
      endogenous photoreceptors. Here, we describe the development of the first
      synthetic light-responsive system for the targeted control of gene expression in
      mammalian and plant cells that responds to the green range of the light spectrum
      in which plant photoreceptors have minimal activity. We first engineered a system
      based on the light-sensitive bacterial transcription factor CarH and its cognate
      DNA operator sequence CarO from Thermus thermophilus to control gene expression
      in mammalian cells. The system was functional in various mammalian cell lines,
      showing high induction (up to 350-fold) along with low leakiness, as well as high
      reversibility. We quantitatively described the systems characteristics by the
      development and experimental validation of a mathematical model. Finally, we
      transferred the system into A. thaliana protoplasts and demonstrated gene
      repression in response to green light. We expect that this system will provide
      new opportunities in applications based on synthetic gene networks and will open
      up perspectives for optogenetic studies in mammalian and plant cells.

PMID- 29634241
TI  - Plazomicin Retains Antibiotic Activity against Most Aminoglycoside Modifying
      Enzymes.
AB  - Plazomicin is a next-generation, semisynthetic aminoglycoside antibiotic
      currently under development for the treatment of infections due to multidrug
      resistant Enterobacteriaceae. The compound was designed by chemical modification
      of the natural product sisomicin to provide protection from common aminoglycoside
      modifying enzymes that chemically alter these drugs via N-acetylation, O
      adenylylation, or O-phosphorylation. In this study, plazomicin was profiled
      against a panel of isogenic strains of Escherichia coli individually expressing
      twenty-one aminoglycoside resistance enzymes. Plazomicin retained antibacterial
      activity against 15 of the 17 modifying enzyme-expressing strains tested.
      Expression of only two of the modifying enzymes, aac(2')-Ia and aph(2")-IVa,
      decreased plazomicin potency. On the other hand, expression of 16S rRNA ribosomal
      methyltransferases results in a complete lack of plazomicin potency. In vitro
      enzymatic assessment confirmed that AAC(2')-Ia and APH(2'')-IVa (aminoglycoside
      acetyltransferase, AAC; aminoglycoside phosphotransferase, APH) were able to
      utilize plazomicin as a substrate. AAC(2')-Ia and APH(2'')-IVa are limited in
      their distribution to Providencia stuartii and Enterococci, respectively. These
      data demonstrate that plazomicin is not modified by a broad spectrum of common
      aminoglycoside modifying enzymes including those commonly found in
      Enterobacteriaceae. However, plazomicin is inactive in the presence of 16S rRNA
      ribosomal methyltransferases, which should be monitored in future surveillance
      programs.

PMID- 29634243
TI  - Modified Organosilica Core-Shell Nanoparticles for Stable pH Sensing in
      Biological Solutions.
AB  - Continuous monitoring using nanoparticle-based sensors has been successfully
      employed in complex biological systems, yet the sensors still suffer from poor
      long-term stability partially because of the scaffold materials chosen to date.
      Organosilica core-shell nanoparticles containing a mixture of covalently
      incorporated pH-sensitive (shell) and pH-insensitive (core) fluorophores is
      presented as a continuous pH sensor for application in biological media. In
      contrast to previous studies focusing on similar materials, we sought to
      investigate the sensor characteristics (dynamic range, sensitivity, response
      time, stability) as a function of material properties. The ratio of the
      fluorescence intensities at specific wavelengths was found to be highly sensitive
      to pH over a physiologically relevant range (4.5-8) with a response time of <100
      ms, significantly faster than that of previously reported response times using
      silica-based particles. Particles produced stable, pH-specific signals when
      stored at room temperature for more than 80 days. Finally, we demonstrated that
      the nanosensors successfully monitored the pH of a bacterial culture over 15 h
      and that pH changes in the skin of mouse cadavers could also be observed via in
      vivo fluorescence imaging following subcutaneous injection. The understanding
      gained from linking sensor characteristics and material properties will inform
      the next generation of optical nanosensors for continuous-monitoring
      applications.

PMID- 29634244
TI  - Natural Sugar: A Green Assistance To Efficiently Exfoliate Inorganic Layered
      Nanomaterials.
AB  - We have demonstrated that natural sugars can efficiently exfoliate inorganic
      layered nanomaterials with direct stirring. The representative transition-metal
      dichalcogenides (MoS2 and WS2), transition-metal oxide (MoO3), and graphene were
      explored, and the formation of ultrathin nanosheets was verified. Glucose and
      MoS2 selected each other as the perfect partner with superior exfoliation and
      excellent properties. The obtained inorganic layered nanosheets possess favorable
      stability and dispersity, which renders it suitable for direct homogeneous liquid
      applications, such as catalytic activities and sensors. With a high-throughput
      and green process, the sugar-assisted method may offer new ideas for inorganic
      layered nanomaterials synthesis and applications in a more ecofriendly way.

PMID- 29634245
TI  - Nutritional Attributes, Substitutability, Scalability, and Environmental
      Intensity of an Illustrative Subset of Current and Future Protein Sources for
      Aquaculture Feeds: Joint Consideration of Potential Synergies and Trade-offs.
AB  - Aquaculture is anticipated to play an increasingly important role in global food
      security because it may represent one of the best opportunities to increase the
      availability of healthy animal protein in the context of resource and
      environmental constraints. However, the growth and sustainability of the
      aquaculture industry faces important bottlenecks with respect to feed resources,
      which may be derived from diverse sources. Here, using a small but representative
      subset of potential aquafeed inputs (which we selected to highlight a range of
      relevant attributes), we review a core suite of considerations that need to be
      accommodated in concert in order to overcome key bottlenecks to the continued
      development and expansion of the aquaculture industry. Specifically, we evaluate
      the nutritional attributes, substitutability, scalability, and resource and
      environmental intensity of each input. On this basis, we illustrate a range of
      potential synergies and trade-offs within and across attributes that are
      characteristic of ingredient types. We posit that the recognition and management
      of such synergies and trade-offs is imperative to satisfying the multi-objective
      decision-making associated with sustainable increases in future aquaculture
      production.

PMID- 29634246
TI  - Use of a Compact Tripodal Tris(bipyridine) Ligand to Stabilize a Single-Metal
      Centered Chirality: Stereoselective Coordination of Iron(II) and Ruthenium(II) on
      a Semirigid Hexapeptide Macrocycle.
AB  - Fe(II)-coordinating hexapeptides containing three 2,2'-bipyridine moieties as
      side chains were designed and synthesized. A cyclic hexapeptide having three
      [(2,2'-bipyridin)-5-yl]-d-alanine (d-Bpa5) residues, in which d-Bpa5 and Gly are
      alternately arranged with 3-fold rotational symmetry, coordinated with Fe(II) to
      form a 1:1 octahedral Fe(II)-peptide complex with a single facial-Lambda
      configuration of the metal-centered chirality. NMR spectroscopy and molecular
      dynamics simulations revealed that the Fe(II)-peptide complex has an apparent C3
      symmetric conformations on the NMR time scale, while the peptide backbone is
      subject to dynamic conformational exchange between three asymmetric beta/gamma
      conformations and one C3-symmetric gamma/gamma/gamma conformation. The semirigid
      cyclic hexapeptide preferentially arranged these conformations of the small
      octahedral Fe(II)-bipyridine complex, as well as the Ru(II) congener, to underpin
      the single configuration of the metal-centered chirality.

PMID- 29634248
TI  - Unravelling the Excellent Chemical Stability and Bioavailability of Solvent
      Responsive Curcumin-Loaded 2-Ethyl-2-oxazoline-grad-2-(4-dodecyloxyphenyl)-2
      oxazoline Copolymer Nanoparticles for Drug Delivery.
AB  - A new gradient copolymer has been synthesized by the living cationic ring-opening
      polymerization of hydrophilic 2-ethyl-2-oxazoline with lipophilic 2-(4
      dodecyloxyphenyl)-2-oxazoline (EtOx-grad-DPOx). The prepared copolymer is capable
      of assembling in water to yield polymeric nanoparticles that are successfully
      loaded with an anticancer agent, curcumin. Self-assembly of the copolymer was
      found to be tuned by the polarity as well as the hydrogen bonding ability of
      solvents. Solvent took distinctive role in the preparation of unloaded and
      curcumin-loaded nanoparticles. The stability of the nanoparticles was increased
      by curcumin loading promoted by curcumin-polymer interactions. Further, the
      chemical stability of curcumin in water is largely enhanced inside the polymeric
      nanoparticles. Curcumin-loaded (EtOx-grad-DPOx) copolymer nanoparticles showed
      excellent stability in the biological medium, low cytotoxicity, and concentration
      dependent uptake by U87 MG and HeLa cells, which indicate the possibility of
      their efficient application in drug delivery.

PMID- 29634247
TI  - Dynamic Consequences of Mutation of Tryptophan 215 in Thrombin.
AB  - Thrombin normally cleaves fibrinogen to promote coagulation; however, binding of
      thrombomodulin to thrombin switches the specificity of thrombin toward protein C,
      triggering the anticoagulation pathway. The W215A thrombin mutant was reported to
      have decreased activity toward fibrinogen without significant loss of activity
      toward protein C. To understand how mutation of Trp215 may alter thrombin
      specificity, hydrogen-deuterium exchange experiments (HDXMS), accelerated
      molecular dynamics (AMD) simulations, and activity assays were carried out to
      compare the dynamics of Trp215 mutants with those of wild type (WT) thrombin.
      Variation in NaCl concentration had no detectable effect on the sodium-binding
      (220sCT) loop, but appeared to affect other surface loops. Trp215 mutants showed
      significant increases in amide exchange in the 170sCT loop consistent with a loss
      of H-bonding in this loop identified by the AMD simulations. The W215A thrombin
      showed increased amide exchange in the 220sCT loop and in the N-terminus of the
      heavy chain. The AMD simulations showed that a transient conformation of the
      W215A thrombin has a distorted catalytic triad. HDXMS experiments revealed that
      mutation of Phe227, which engages in a pi-stacking interaction with Trp215, also
      caused significantly increased amide exchange in the 170sCT loop. Activity assays
      showed that only the F227V mutant had wild type catalytic activity, whereas all
      other mutants showed markedly lower activity. Taken together, the results explain
      the reduced pro-coagulant activity of the W215A mutant and demonstrate the
      allosteric connection between Trp215, the sodium-binding loop, and the active
      site.

PMID- 29634249
TI  - Composition and Band Gap Tailoring of Crystalline (GaN)1- x(ZnO) x Solid Solution
      Nanowires for Enhanced Photoelectrochemical Performance.
AB  - Photoelectrochemical water splitting has emerged as an effective artificial
      photosynthesis technology to generate clean energy of H2 from sunlight. The core
      issue in this reaction system is to develop a highly efficient photoanode with a
      large fraction of solar light absorption and greater active surface area. In this
      work, we take advantage of energy band engineering to synthesize (GaN)1- x(ZnO) x
      solid solution nanowires with ZnO contents ranging from 10.3% to 47.6% and
      corresponding band gap tailoring from 3.08 to 2.77 eV on the basis of the Au
      assisted VLS mechanism. The morphology of nanowires directly grown on the
      conductive substrate facilitates the charge transfer and simultaneously improves
      the surface reaction sites. As a result, a photocurrent approximately 10 times
      larger than that for a conventional powder-based photoanode is obtained, which
      indicates the potential of (GaN)1- x(ZnO) x nanowires in the preparation of
      superior photoanodes for enhanced water splitting. It is anticipated that the
      water-splitting capability of (GaN)1- x(ZnO) x nanowire can be further increased
      through alignment control for enhanced visible light absorption and reduction of
      charge transfer resistance.

PMID- 29634250
TI  - Conjugate Addition-Enantioselective Protonation of N-Aryl Glycines to alpha
      Branched 2-Vinylazaarenes via Cooperative Photoredox and Asymmetric Catalysis.
AB  - An enantioselective protonation strategy has been successfully applied to the
      synthesis of chiral alpha-tertiary azaarenes. With a dual catalytic system
      involving a chiral phosphoric acid and a dicyanopyrazine-derived chromophore
      (DPZ) photosensitizer that is mediated by visible light, a variety of alpha
      branched 2-vinylpyridines and 2-vinylquinolines with N-aryl glycines underwent a
      redox-neutral, radical conjugate addition-protonation process and provided
      valuable chiral 3-(2-pyridine/quinoline)-3-substituted amines in high yields with
      good to excellent enantioselectivities (up to >99% ee). An application of this
      methodology to a two-step synthesis of the enantiomerically pure medicinal
      compound pheniramine (Avil) is also presented.

PMID- 29634251
TI  - Glycocalyx-Mimicking Nanoparticles Improve Anti-PD-L1 Cancer Immunotherapy
      through Reversion of Tumor-Associated Macrophages.
AB  - Immune checkpoint blockade by anti-PD-L1 monoclonal antibody (alphaPD-L1) has
      achieved unprecedented clinical benefits in certain cancers, whereas the
      therapeutic efficacy is often hindered by immunosuppressive tumor
      microenvironment mediated by tumor-associated macrophages (TAMs), which leads to
      innate resistance to this approach. To improve checkpoint blockade efficacy, the
      amphiphilic diblock copolymers poly(mannopyranoside/galactopyranoside
      methacrylate)- block-polystyrene are prepared by RAFT polymerization, which are
      sequentially self-assembled into glycocalyx-mimicking nanoparticles (GNPs) to
      neutralize TAMs. It is shown that GNPs can be specifically internalized by TAMs
      via lectin receptors, which results in upregulation of immunostimulatory IL-12
      and downregulation of immunosuppressive IL-10, arginase 1, and CCL22, indicating
      functional reversion of protumor TAMs toward antitumor phenotype. The reversion
      of TAMs is proved to be mainly controlled by suppressing STAT6 and activating NF
      kappaB phosphorylation. In vivo therapeutic studies have demonstrated that GNPs
      significantly enhance the therapeutic efficacy of alphaPD-L1 cancer therapy by
      reduction of tumor burden. Moreover, combination therapies with GNPs and alphaPD
      L1 greatly improve immunosuppressive tumor microenvironment by reciprocal
      modulation of tumor-infiltrating effector and regulatory T cells. Notably, for
      the first time, our results demonstrate the reversion of TAMs and improvement of
      alphaPD-L1 cancer therapy by synthetic carbohydrate-containing nanomaterials.
      This research highlights a promising strategy for optimizing immune checkpoint
      blockade in cancer immunotherapy.

PMID- 29634253
TI  - A Dinuclear Iridium(V,V) Oxo-Bridged Complex Characterized Using a Bulk
      Electrolysis Technique for Crystallizing Highly Oxidizing Compounds.
AB  - We report a general method for the preparation and crystallization of highly
      oxidized metal complexes that are difficult to prepare and handle by more
      conventional means. This method improves typical bulk electrolysis and
      crystallization conditions for these reactive species by substituting oxidation
      prone organic electrolytes and precipitants with oxidation-resistant compounds.
      Specifically, we find that CsPF6 is an effective inert electrolyte in
      acetonitrile, and appears to have general applicability to electrochemical
      studies in this solvent. Likewise, CCl4 is not only an oxidation-resistant
      precipitant for crystallization from MeCN but it also enters the lattice. In this
      way, we synthesized and characterized an Ir(V,V) mono-MU-oxo dimer which only
      forms at a very high potential (1.9 V vs NHE). This compound, having the highest
      isolated oxidation state in this redox-active system, cannot be formed
      chemically. DFT calculations show that the oxidation is centered on the Ir-O-Ir
      core and facilitated by strong electron-donation from the pyalk (2-(2-pyridinyl)
      2-propanolate) ligand. TD-DFT simulations of the UV-visible spectrum reveal that
      its royal blue color arises from electron excitations with mixed LMCT and Laporte
      allowed d-d character. We have also crystallographically characterized a related
      monomeric Ir(V) complex, similarly prepared by oxidizing a previously reported
      Ir(IV) compound at 1.7 V, underscoring the general applicability of this method.

PMID- 29634252
TI  - Higher Flexibility of Glu-172 Explains the Unusual Stereospecificity of
      Glyoxalase I.
AB  - Despite many studies during the latest two decades, the reason for the unusual
      stereospecificity of glyoxalase I (GlxI) is still unknown. This metalloenzyme
      converts both enantiomers of its natural substrate to only one enantiomer of its
      product. In addition, GlxI catalyzes reactions involving some substrate and
      product analogues with a stereospecificity similar to that of its natural
      substrate reaction. For example, the enzyme exchanges the pro- S, but not the pro
      R, hydroxymethyl proton of glutathiohydroxyacetone (HOC-SG) with a deuterium
      from D2O. To find some clues to the unusual stereospecificity of GlxI, we have
      studied the stereospecific proton exchange of the hydroxymethyl proton of HOC-SG
      by this enzyme. We employed density functional theory and molecular dynamics (MD)
      simulations to study the proton exchange mechanism and origin of the
      stereospecificity. The results show that a rigid cluster model with the same
      flexibility for the two active-site glutamate residues cannot explain the unusual
      stereospecificity of GlxI. However, using a cluster model with full flexibility
      of Glu-172 or a larger model with the entire glutamates, extending the backbone
      into the neighboring residues, the results showed that there is no way for HOC-SG
      to exchange its protons if the alcoholic proton is directed toward Glu-99.
      However, if the hydroxymethyl proton instead is directed toward the more flexible
      Glu-172, we find a catalytic reaction mechanism for the exchange of the HS proton
      by a deuterium, in accordance with experimental findings. Thus, our results
      indicate that the special stereospecificity of GlxI is caused by the more
      flexible environment of Glu-172 in comparison to that of Glu-99. This higher
      flexibility of Glu-172 is also confirmed by MD simulations. We propose a reaction
      mechanism for the stereospecific proton exchange of the hydroxymethyl proton of
      HOC-SG by GlxI with an overall energy barrier of 15 kcal/mol.

PMID- 29634254
TI  - Creation of Linear Carbon Dot Array with Improved Optical Properties through
      Controlled Covalent Conjugation with DNA.
AB  - Controlled conjugation of fluorescent carbon dots (CDs) with DNA and subsequent
      fabrication of the CDs into an array through hybridization mediated self-assembly
      in the solution phase is reported. Covalent conjugation of CD with DNA and the
      subsequent array formation change the mobility of the CD-DNA array in gel
      electrophoresis and HPLC significantly. Interspatial distance in the CD-DNA array
      is tuned by the DNA sequence length and maintained at ~8 +/- 0.3 nm as revealed
      by electron microscopy studies. An increase in fluorescence lifetime by ~2 ns was
      observed for the CD-DNA array compared to a solitary CD, vis-a-vis better imaging
      prospects of HEK293 cells by the former. Thus, the array displays improved
      fluorescence and unhindered cell penetration.

PMID- 29634256
TI  - Synthetic Strategies for the Synthesis of Ternary Uranium(IV) and Thorium(IV)
      Fluorides.
AB  - A series of new U(IV) and Th(IV) fluorides, Na7U6F31 (1), NaUF5 (2), NaU2F9 (3),
      KTh2F9 (4), NaTh2F9 (5), (H3O)Th3F13 (6), and (H3O)U3F13 (7), was obtained using
      hydrothermal and low-temperature flux methods. Mild hydrothermal reactions with
      uranyl acetate as a precursor yielded 1, 7, and the monoclinic polymorph of
      NaU2F9, whereas direct reactions between UF4 and NaF led to the formation of 2
      and orthorhombic NaU2F9 (3). This highlights an unexpected difference in reaction
      products when different starting uranium sources are used. All seven compounds
      were characterized by single-crystal X-ray diffraction, and their structures are
      compared on the basis of cation topology, revealing a close topological
      resemblance between fluorides on the basis of the layers observed in NaUF5(H2O).
      Phase-pure samples of 1, 2, and both polymorphs of NaU2F9 were obtained, and
      their spectroscopic and magnetic properties were measured. The UV-vis data are
      dominated by the presence of U4+ cations and agree well with the electronic
      transitions. Effective magnetic moments of the studied compounds were found to
      range from 3.08 to 3.59 MUB.

PMID- 29634255
TI  - Multifunctional Theranostic Nanoplatform Based on Fe-mTa2O5@CuS-ZnPc/PCM for
      Bimodal Imaging and Synergistically Enhanced Phototherapy.
AB  - Multifunctional nanotheranostic agent with high performance for tumor site
      specific generation of singlet oxygen (1O2) as well as imaging-guidance is
      crucial to laser-mediated photodynamic therapy. Here, we introduced a versatile
      strategy to design a smart nanoplatform using phase change material (PCM) to
      encapsulate photosensitizer (zinc phthalocyanine, ZnPc) in copper sulfide loaded
      Fe-doped tantalum oxide (Fe-mTa2O5@CuS) nanoparticles. When irradiated by 808 nm
      laser, the PCM is melted due to the hyperthermia effect from CuS nanoparticles,
      inducing the release of ZnPc to produce toxic 1O2 triggered by 650 nm light with
      very low power density (5 mW/cm2). Then, the produced heat and toxic 1O2 can kill
      tumor cells in vitro and in vivo effectively. Furthermore, the special properties
      of Fe-mTa2O5 endow the nanoplatform with excellent computed tomography (CT) and
      T1-weighted magnetic resonance imaging ( T1-MRI) performance for guiding and real
      time monitoring of therapeutic effect. This work presents a feasible way to
      design smart nanoplatform for controllable generation of heat and 1O2, achieving
      CT/ T1-MRI dual-modal imaging-guided phototherapy.

PMID- 29634257
TI  - Electron-Donating Phenolic and Electron-Accepting Quinone Moieties in Peat
      Dissolved Organic Matter: Quantities and Redox Transformations in the Context of
      Peat Biogeochemistry.
AB  - Electron-donating phenolic and electron-accepting quinone moieties in peat
      dissolved organic matter (DOM) are considered to play key roles in processes
      defining carbon cycling in northern peatlands. This work advances a flow
      injection analysis system coupled to chronoamperometric detection to allow for
      the simultaneous and highly sensitive determination of these moieties in dilute
      DOM samples. Analysis of anoxic pore water and oxic pool water samples collected
      across an ombrotrophic bog in Sweden demonstrated the presence of both phenolic
      and quinone moieties in peat DOM. The pore water DOM had higher quantities of
      phenolic but not quinone moieties compared with commonly used model aquatic and
      terrestrial DOM isolates. Significantly lower phenol content in DOM from oxic
      pools than DOM from anoxic pore waters indicated oxidative DOM processing in the
      pools. Consistently, treatment of peat DOM with laccase, a phenol-oxidase, under
      oxic conditions resulted in an irreversible removal of phenols and reversible
      oxidation of hydroquinones to quinones. Electron transfer to peat DOM was fully
      reversible over an electrochemical reduction and subsequent O2-reoxidation cycle,
      supporting that quinones in peat DOM serve as regenerable microbial electron
      acceptors in peatlands. The results advance our understanding of redox processes
      involving phenolic and quinone DOM moieties and their roles in northern peatland
      carbon cycling.

PMID- 29634258
TI  - 3D Long-Range Triplet Migration in a Water-Stable Metal-Organic Framework for
      Upconversion-Based Ultralow-Power in Vivo Imaging.
AB  - Triplet-triplet annihilation upconversion (TTA-UC) has gained increasing
      attention because it allows for harvesting of low-energy photons in the solar
      spectrum with high efficiency in relevant applications including solar cells and
      bioimaging. However, the utilization of conventional TTA-UC systems for low-power
      bioapplications is significantly hampered by their general incompatibility and
      low efficiency in aqueous media. Herein we report a metal-organic framework (MOF)
      as a biocompatible nanoplatform for TTA-UC to realize low-power in vivo imaging.
      Our MOF consists of a porphyrinic sensitizer in an anthracene-based Zr-MOF as a
      TTA-UC platform. In particular, closely aligned chromophores in the MOF
      facilitate a long-range 3D triplet diffusion of 1.6 MUm allowing efficient energy
      migration in water. The tunable ratio between sensitizer and annihilator by our
      synthetic method also allows an optimization of the system for maximized TTA-UC
      efficiency in water at a very low excitation power density. Consequently, the low
      power imaging of lymph node in a live mouse was successfully demonstrated with an
      excellent signal-to-noise ratio (SNR > 30 at 5 mW cm-2).

PMID- 29634259
TI  - Interaction of Soybean 7S Globulin Peptide with Cell Membrane Model via
      Isothermal Titration Calorimetry, Quartz Crystal Microbalance with Dissipation,
      and Langmuir Monolayer Study.
AB  - To understand the underlying molecular mechanism of the cholesterol-lowering
      effect of soybean 7S globulins, the interactions of their pepsin-released
      peptides (7S-peptides) with cell membrane models consisting of
      dipalmitoylphosphatidylcholine (DPPC), dioleoylphosphatidylcholine (DOPC), and
      cholesterol (CHOL) were systematically studied. The results showed that 7S
      peptides were bound to DPPC/DOPC/CHOL liposomes mainly through van der Waals
      forces and hydrogen bonds, and the presence of higher CHOL concentrations
      enhanced the binding affinity (e.g., DPPC/DOPC/CHOL = 1:1:0, binding ratio =
      0.114; DPPC/DOPC/CHOL = 1:1:1, binding ratio = 2.02). Compression isotherms
      indicated that the incorporation of 7S-peptides increased the DPPC/DOPC/CHOL
      monolayer fluidity and the lipid raft size. The presence of CHOL accelerated the
      7S-peptide accumulation on lipid rafts, which could serve as platforms for
      peptides to develop into beta-sheet rich structures. These results allow us to
      hypothesize that 7S-peptides may indirectly influence membrane protein functions
      via altering the membrane organization in the enterocytes.

PMID- 29634260
TI  - Structural Modification of Natural Product Ganomycin I Leading to Discovery of a
      alpha-Glucosidase and HMG-CoA Reductase Dual Inhibitor Improving Obesity and
      Metabolic Dysfunction in Vivo.
AB  - It is a great challenge to develop drugs for treatment of metabolic syndrome.
      With ganomycin I as a leading compound, 14 meroterpene derivatives were
      synthesized and screened for their alpha-glucosidase and HMG-CoA reductase
      inhibitory activities. As a result, a alpha-glucosidase and HMG-CoA reductase
      dual inhibitor (( R, E)-5-(4-( tert-butyl)phenyl)-3-(4,8-dimethylnona-3,7-dien-1
      yl)furan-2(5 H)-one, 7d) with improved chemical stability and long-term safety
      was obtained. Compound 7d showed multiple and strong in vivo efficacies in
      reducing weight gain, lowering HbAlc level, and improving insulin resistance and
      lipid dysfunction in both ob/ob and diet-induced obesity (DIO) mice models.
      Compound 7d was also found to reduce hepatic steatosis in ob/ob model. 16S rRNA
      gene sequencing, SCFA, and intestinal mucosal barrier function analysis indicated
      that gut microbiota plays a central and causative role in mediating the multiple
      efficacies of 7d. Our results demonstrate that 7d is a promising drug candidate
      for metabolic syndrome.

PMID- 29634261
TI  - Synthesis and Desymmetrization of meso Tricyclic Systems Derived from Benzene
      Oxide.
AB  - Ozonolysis of the Diels-Alder adducts derived from benzene oxides and N
      alkylmaleimides resulted in fully substituted, meso bicyclic systems bearing six
      contiguous stereocenters, isolated as diols upon reductive workup with NaBH4.
      Variation in the workup allowed for isolation of two different diastereoisomers,
      through double epimerization of the imide stereocenters. Desymmetrization of the
      resulting meso diols via asymmetric nucleophilic epoxide opening and acylation
      reactions provided access to highly substituted, enantioenriched fused rings.

PMID- 29634262
TI  - Organocatalytic Asymmetric Domino Michael/Acyl Transfer Reaction between
      gamma/delta-Hydroxyenones and alpha-Nitroketones.
AB  - An organocatalytic asymmetric domino Michael/acyl transfer reaction has been
      developed between gamma/delta-hydroxyenones and alpha-nitroketones. Cinchona
      alkaloid derived bifunctional amino-squaramide catalysts were found to be the
      best catalysts for this reaction. The products having nitro, keto, and ester
      functionalities were obtained in high yields and with excellent
      enantioselectivities, and also a few synthetic transformations have been
      demonstrated.

PMID- 29634263
TI  - Role of Electron-Donating and Electron-Withdrawing Groups in Tuning the
      Optoelectronic Properties of Difluoroboron-Napthyridine Analogues.
AB  - Five napthyridine-based fluorine-boron (BF2-napthyridine) conjugated compounds
      have been theoretically designed, and subsequently, their photophysical
      properties are investigated. The influence of electron-donating and electron
      withdrawing groups attached with the N?C?O moiety of BF2-napthyridine molecule
      has been interpreted. The optoelectronic properties, including absorption spectra
      and emission spectra of the BF2-napthyridine derivatives are studied using
      density functional theory (DFT) and time-dependent density functional theory (TD
      DFT) based methods. Different characteristics, such as HOMO-LUMO gap, molecular
      orbital density, ionization potential, electron affinity, and reorganization
      energy for hole and electron, are calculated. All these molecules show excellent
      pi-electron delocalization. TD-DFT results illustrate that the amine-substituted
      BF2-napthyridine derivative has the highest absorption and emission maxima; it
      also shows a maximum Stoke shift. These results are well-correlated with the
      structural parameters and calculated HOMO-LUMO gap. Moreover, it is found that
      introduction of an electron-donating group into the BF2-napthyridine complex
      improves the hole transport properties and provides useful clues in designing new
      materials for organic light emitting diodes (OLED). As a whole, this work
      demonstrates that electron-donating and electron-withdrawing groups in BF2
      derivatives can extend their effectiveness toward designing of OLED materials,
      vitro cellular studies, ex vivo assays, and in vivo imaging agents.

PMID- 29634264
TI  - Development of a Sono-Assembled, Bifunctional Soy Peptide Nanoparticle for
      Cellular Delivery of Hydrophobic Active Cargoes.
AB  - Soy proteins are prone to aggregate upon proteolysis, hindering their sustainable
      development in food processing. Here, a continuous work on the large insoluble
      peptide aggregates was carried out, aiming to develop a new type of soy peptide
      based nanoparticle (SPN) for active cargo delivery. Sono-assembled SPN in
      spherical appearance and core-shell structure maintained by noncovalent
      interactions was successfully fabricated, exhibiting small particle size (103.95
      nm) in a homogeneous distribution state (PDI = 0.18). Curcumin as a model cargo
      was efficiently encapsulated into SPN upon sonication, showing high water
      dispersity (129.6 mg/L, 104 higher than its water solubility) and storage
      stability. Additionally, the pepsin-resistant SPN contributed to the controlled
      release of curcumin at the intestinal phase and thus significantly improved the
      bioaccessibility. Encapsulated curcumin was effective in protecting glutamate
      induced toxicity in PC12 cells, where the matrix SPN can simultaneously reduce
      lipid peroxidation and elevate antioxidant enzymes levels, innovatively
      demonstrating its bifunctionality during cellular delivery.

PMID- 29634265
TI  - Significant Reduction of the Expression of Peach ( Prunus persica L. Batsch)
      Allergen-Encoding Genes by Fruit Bagging with Opaque Paper.
AB  - Freshly consumed peaches ( Prunus persica L. Batsch) can cause allergic reactions
      in the worldwide population because of the presence of four classes of allergens
      (Pru p 1, Pru p 2, Pru p 3, and Pru p 4). Fruit bagging has been widely practiced
      in peach cultivation to improve fruit quality; however, its effect on the
      expression of peach allergen-encoding genes remains unknown. In this study, the
      influence of fruit bagging with opaque paper bags on the major peach allergen
      encoding genes, including Pru p 1.01, Pru p 1.06B, Pru p 2.01B, Pru p 2.02, Pru p
      3.01, Pru p 4.01, and Pru p 4.02, were measured by means of real-time PCR. A
      significant reduction in transcript accumulation was observed for all of the
      selected genes in the epicarps of the bagged peach fruits, whereas slight
      increases were observed in the mesocarps for these genes, with the two exceptions
      of Pru p 2.02 and Pru p 3.01. For most of these genes, much higher transcripts
      were determined in the epicarps than in the mesocarps. Taken together, a
      significant reduction in the transcription rate of the allergen-encoding genes in
      the whole peach fruit was achieved by shading with opaque paper bags. According
      to these data, modifications in growing practices of peach may help to obtain
      fruits with lower levels of allergens and thus contribute to reducing potential
      allergenic risks in consumers.

PMID- 29634266
TI  - Computational Study of Molecular Hydrogen Adsorption over Small (MO2) n
      Nanoclusters (M = Ti, Zr, Hf; n = 1 to 4).
AB  - Hydrogen adsorption on small group 4 metal oxide clusters for both the singlet
      and the first excited triplet states have been investigated by density functional
      theory and correlated molecular orbital theory at the coupled cluster CCSD(T)
      level. The reaction starts with hydrogen physisorption on a metal center followed
      by formation of metal hydride/hydroxides due to splitting H2 into H- and H+. The
      hydrogen physisorption energies are predicted to be -1 to -8 kcal/mol for the
      singlet and -1 to -26 kcal/mol for the triplet, respectively. The formation of
      metal hydride/hydroxides does not involve redox processes. Chemisorption leading
      to formation of metal hydride/hydroxides is exothermic by -10 to -50 kcal/mol for
      the singlet, and exothermic by up to -60 kcal/mol for the triplet. The predicted
      energy barriers are less than 20 kcal/mol. Formation of metal dihydroxides from
      the metal hydride/hydroxides is generally endothermic for the monomer and dimer
      and is exothermic for the trimer and tetramer. Formation of the dihydroxide is a
      proton coupled electron transfer (PCET) process. The singlet energy barriers for
      the H--> H+ transfer process are predicted to be 35-60 kcal/mol, in comparison to
      triplet energy barriers of less than 15 kcal/mol for the H* -> H+ transfer
      process. For trimers and tetramers, there exist two different pathways: the first
      is a direct pathway with PCET to a terminal oxygen and the second is a two-step
      pathway with initial formation of a bridge OH group followed by a proton transfer
      to generate a terminal OH group. For the singlet, the two-step pathway is
      preferred for M = Ti and the direct pathway is more favorable for M = Zr and Hf.
      The two-step pathway is always preferred for the triplet as one-electron transfer
      is always more likely than two-electron transfer in the direct pathway.

PMID- 29634267
TI  - Synthesis of 3,5-Disubstituted BODIPYs Bearing N-Containing Five-Membered
      Heteroaryl Groups via Nucleophilic C-N Bond Formation.
AB  - Aromatic substitution reactions were applied to the divergent synthesis of a
      series of symmetrically and unsymmetrically 3,5-disubstituted BODIPYs bearing N
      heteroaryl groups. Furthermore, the effect of N-heteroaryl substituents at the 3-
      and 5-positions on the optical and photophysical properties of the BODIPY pi
      electron system was elucidated.

PMID- 29634268
TI  - Phenolic Pollutant Uptake Properties of Molecular Templated Polymers Containing
      beta-Cyclodextrin.
AB  - Templated (T) and nontemplated (NT) cross-linked materials containing beta
      cyclodextrin (beta-CD) and epichlorohydrin (EPH) were prepared at variable beta
      CD-EPH ratios (1:15, 1:20, and 1:25) in the presence and absence of a molecular
      template (toluene). The structural characterization of the materials was carried
      out using spectroscopy (Fourier transform infrared, solids 13C NMR, and scanning
      electron microscopy) and thermogravimetric analysis. The adsorption properties
      were studied with phenol-based adsorbates (2,4,6-trinitrophenol (TNP) and p
      nitrophenol (PNP)) at equilibrium and dynamic conditions. The monolayer
      adsorption capacity ( Qm) varied for the T-polymer/TNP systems ( Qm = 0.10-0.95
      mmol/g) and NT-polymer/TNP systems ( Qm = 0.23-0.83 mmol/g). The range of Qm
      values for the T-polymer/PNP systems (0.26-0.62 mmol/g) exceeded that of the NT
      polymer/PNP systems (0.23-0.40 mmol/g). The kinetic uptake profiles for the
      polymers and phenolphthalein were reliably described by the pseudo-first-order
      model. The beta-CD inclusion site accessibility for the polymers varied from 15
      to 20%, according to the level of cross-linking, where the accessibility of the T
      polymers exceeded that of the NT-polymers. The structural characterization and
      phenol adsorption properties provide complementary support for the role of
      tunable polymer morphology in adsorption processes. The role of two-site binding
      was demonstrated for linear and globular polymer materials according to their
      unique adsorption properties with phenols of variable size and hydrophile
      lipophile character.

PMID- 29634269
TI  - Drimane Sesquiterpenoids Noncompetitively Inhibit Human alpha4beta2 Nicotinic
      Acetylcholine Receptors with Higher Potency Compared to Human alpha3beta4 and
      alpha7 Subtypes.
AB  - The drimane sesquiterpenoids drimenin, cinnamolide, dendocarbin A, and polygodial
      were purified from the Canelo tree ( Drimys winteri) and chemically characterized
      by spectroscopic methods. The pharmacological activity of these natural compounds
      were determined on halpha4beta2, halpha3beta4, and halpha7 nicotinic
      acetylcholine receptors (AChRs) by Ca2+ influx measurements. The results
      established that drimane sesquiterpenoids inhibit AChRs with the following
      selectivity: halpha4beta2 > halpha3beta4 > halpha7. In the case of halpha4beta2
      AChRs, the following potency rank order was determined (IC50's in MUM): drimenin
      (0.97 +/- 0.35) > cinnamolide (1.57 +/- 0.36) > polygodial (62.5 +/- 19.9) ?
      dendocarbin A (no activity). To determine putative structural features underlying
      the differences in inhibitory potency at halpha4beta2 AChRs, additional structure
      activity relationship and molecular docking experiments were performed. The Ca2+
      influx and structural results supported a noncompetitive mechanism of inhibition,
      where drimenin interacted with luminal and nonluminal (TMD-beta2 intrasubunit)
      sites. The structure-activity relationship results, i.e., the lower the ligand
      polarity, the higher the inhibitory potency, supported the nonluminal
      interaction. Ligand binding to both sites might inhibit the halpha4beta2 AChR by
      a cooperative mechanism, as shown experimentally ( nH > 1). Drimenin could be
      used as a molecular scaffold for the development of more potent inhibitors with
      higher selectivity for the halpha4beta2 AChR.

PMID- 29634270
TI  - Recovering Intrinsic Fragmental Vibrations Using the Generalized Subsystem
      Vibrational Analysis.
AB  - Normal vibrational modes are generally delocalized over the molecular system,
      which makes it difficult to assign certain vibrations to specific fragments or
      functional groups. We introduce a new approach, the Generalized Subsystem
      Vibrational Analysis (GSVA), to extract the intrinsic fragmental vibrations of
      any fragment/subsystem from the whole system via the evaluation of the
      corresponding effective Hessian matrix. The retention of the curvature
      information with regard to the potential energy surface for the effective Hessian
      matrix endows our approach with a concrete physical basis and enables the normal
      vibrational modes of different molecular systems to be legitimately comparable.
      Furthermore, the intrinsic fragmental vibrations act as a new link between the
      Konkoli-Cremer local vibrational modes and the normal vibrational modes.

PMID- 29634271
TI  - Schincalactones A and B, Two 5/5/6/11/3 Fused Schinortriterpenoids with a 13
      Membered Carbon Ring System from Schisandra incarnata.
AB  - Two novel schinortriterpenoids (SNTs), schincalactones A (1) and B (2), featuring
      a unique 5/5/6/11/3 ring system, together with schincalide B (3), were isolated
      from Schisandra incarnata. Their structures were elucidated by detailed
      spectroscopic analysis, and the absolute configurations of 1 and 3 were confirmed
      by single-crystal X-ray diffraction. Compounds 1 and 2 possess a 13-membered
      carbon ring and are the first examples in the SNT family. Plausible biosynthetic
      pathways of 1-3 were postulated.

PMID- 29634272
TI  - Magnetic Mesoporous Silica Gated with Doped Carbon Dot for Site-Specific Drug
      Delivery, Fluorescence, and MR Imaging.
AB  - Construction of a theranostic agent which integrates multiple modalities with
      different functions into one entity is challenging from a molecular design and
      synthesis perspective. In this context, the present paper reports the fabrication
      of a novel type of multifunctional hybrid nanoparticle composed of magnetic
      gadolinium oxide-iron oxide core, mesoporous silica shell gated with boronic acid
      functionalized highly luminescent carbon quantum dot (BNSCQD). The porous silica
      shell acts as an excellent reservoir for anticancer drug 5-fluorouracil, whereas
      the BNSCQD cap impressively controls the drug transport under simulated
      intracellular environment. Furthermore, recognition and fluorescence turn on
      response of BNSCQD toward cell surface glycan sialyl Lewisa (SLa) enables
      targeted drug release and excellent fluorescence imaging of SLa overexpressed
      HePG2 cancer cells. The r1 and r2 relaxivities of the material are found to be 10
      and 165 mM-1 s-1 which is comparable to commercially available magnetic resonance
      imaging contrast agents. Benefiting from the combined advantages of dual stimuli
      responsive drug release, excellent optical imaging, and MR imaging, this novel
      construct can be a promising theranostic material.

PMID- 29634273
TI  - Controlled Synthesis of C70 Equatorial Multiadducts with Mixed Addends from an
      Equatorial Diadduct: Evidence for an Electrophilic Carbanion.
AB  - Controlled synthesis of the equatorial tetra-, hexa-, and
      octaorgano[70]fullerenes with mixed addends was achieved via the reaction of
      equatorial 7,23-Bn2C70 with MeO- and ArCH2Br. The products were structurally
      characterized by single crystal X-ray diffraction. The regioselectivity of the
      reaction was studied by in situ vis-NIR and Fukui function analysis. A surprising
      electrophilic triorgano[70]fullerene carbanion was shown, and an enhanced
      fluorescence was observed for the mixed octaadducts.

PMID- 29634274
TI  - Aroyl Isocyanates as 1,4-Dipoles in a Formal [4 + 1]-Cycloaddition Approach
      toward Oxazolone Construction.
AB  - A formal phosphine-mediated [4 + 1]-cycloaddition between a 1,2-dicarbonyl and an
      aroyl isocyanate to provide oxazolones bearing a disubstituted C5 center is
      described. By exploiting the carbene-like reactivity of oxyphosphonium enolates
      as C1 synthons and aroyl isocyanates as formal 1,4-dipoles, oxazolones and
      spiroooxindole oxazolones are constructed in high yields (39-99%).

PMID- 29634275
TI  - CysLTR1 Blockage Ameliorates Liver Injury Caused by Aluminum-Overload via
      PI3K/AKT/mTOR-Mediated Autophagy Activation in Vivo and in Vitro.
AB  - Aluminum (Al) is a trivalent cation that can accumulate in animal organs,
      especially in the liver. We previously demonstrated that Al-overload could induce
      liver morphologic aberrations and dysfunction. However, the molecular mechanism
      underlying liver injury caused by Al-overload still remains unknown. In the
      present study, we investigated the relationship between leukotrienes receptors
      and the PI3K/AKT/mTOR pathway in Al-induced liver injury in vivo and in vitro. We
      demonstrated that Al-overload significantly increased the protein expression
      levels of CysLTR1, PI3K, AKT, mTOR, and p62, while significantly decreasing the
      LC3BII protein levels in rat liver; thus, suggesting that the autophagy process
      was inhibited in Al-overloaded rat liver. In addition, MK-571, an inhibitor of
      CysLTR1, effectively protected the human hepatocyte L02 cells against injury
      caused by Al exposure. Moreover, CysLTR1 blockage could significantly down
      regulate the PI3K/AKT/mTOR pathway and activate autophagy. The effect of MK-571
      on cell viability was abolished by the treatment with the autophagy inhibitor
      (wortmannin) but not with the autophagy agonist (rapamycin). Taken together, our
      results indicated that the blockage of the leukotriene receptor of CysLTR1
      promotes autophagy and further reduces hepatocyte death through the PI3K/AKT/mTOR
      pathway inhibition. CysLTR1 thus could represent a potential target for the new
      drug development for chronic noninfective liver injury.

PMID- 29634276
TI  - Nitrate-promoted Selective C-H Fluorination of Benzamides and Benzeneacetamides.
AB  - A versatile and site-selective nitrate-promoted C-H bond fluorination using
      various weak coordinating amides as intrinsic directing groups was developed.
      Diverse tertiary and secondary amides underwent selective aromatic C-H bond
      fluorination, which features broad substrate scope, good regioselectivity, and
      mild conditions. Moreover, the late-stage C-H bond fluorination of the
      challenging benzeneacetamides via distal directing was reported for the first
      time.

PMID- 29634277
TI  - Polylysine is a Proteostasis Network-Engaging Structural Determinant.
AB  - C-terminal polylysine (PL) can be synthesized from the polyadenine tail of
      prematurely cleaved mRNAs or when a read-though of a stop codon happens. Due to
      the highly positive charge, PL stalls in the electrostatically negative ribosomal
      exit channel. The stalled polypeptide recruits the Ribosome-associated quality
      control (RQC) complex which processes and extracts the nascent chain. Dysfunction
      of the RQC leads to the accumulation of PL-tagged proteins, induction of a stress
      response, and cellular toxicity. Not much is known about the PL-specific aspect
      of protein quality control. Using quantitative mass spectrometry, we uncovered
      the post-ribosomal PL-processing machinery in human cytosol. It encompasses key
      cytosolic complexes of the proteostasis network, such as chaperonin TCP-1 ring
      complexes (TRiC) and half-capped 19S-20S proteasomes. Furthermore, we found that
      the nuclear transport machinery associates with PL, which suggests a novel
      mechanism by which faulty proteins can be compartmentalized in the cell. The
      enhanced nuclear import of a PL-tagged polypeptide confirmed this implication,
      which leads to questions regarding the biological rationale behind it.

PMID- 29634278
TI  - Direct ortho-Selective C-H Functionalization of Carboxybenzyl-Protected
      Arylalkylamines via Ir(III)-Catalyzed C-H Activation.
AB  - A convenient and practical approach to synthesize ortho-alkynylated
      arylalkylamines through ortho-selective C-H functionalization has been developed
      using Cbz-amide as the directing group and Ir(III) as the catalyst. Various
      substrates were well tolerated, affording the corresponding products in moderate
      to good yields. Moreover, preliminary mechanistic study revealed the role of the
      amide as the coordination center to cooperate with the Ir(III) complex during C-H
      activation. Development of this Cbz-amide-promoted CAr-H functionalization offers
      a practical approach with potential applications in organic synthesis.

PMID- 29634281
TI  - Excimer Emission in J-Aggregates.
AB  - An excimer in J-aggregates has been often considered as a self-trapped exciton
      originating from the free exciton excited on the same aggregate and relaxed
      through interaction with vibronic modes. Here we show that other types of
      excimers due to intermolecular off-diagonal interactions can be observed in J
      aggregates of thiamonomethinecyanine dyes. These excimers arise owing to free
      excitons too, but they possess a longer formation time of more than 100 ps,
      indicating migration of free excitons to the excimer formation site, where they
      interact with a guest species in the ground state. Formation of the excimers
      occurs in solutions as a power law of concentration with an exponent of 1.5,
      showing that an excited aggregate should be twice longer than a ground-state
      guest species, consistent with the exciton coherence length of four molecules
      versus one dimer, respectively. Unlike the self-trapped exciton, lower
      temperatures lead to significant suppression of the observed excimer emission.

PMID- 29634280
TI  - Direct Determination of Absolute Absorption Cross Sections at the L-Edge of
      Dilute Mn Complexes in Solution Using a Transmission Flatjet.
AB  - The 3d transition metals play a pivotal role in many charge transfer processes in
      catalysis and biology. X-ray absorption spectroscopy at the L-edge of metal sites
      probes metal 2p-3d excitations, providing key access to their valence electronic
      structure, which is crucial for understanding these processes. We report L-edge
      absorption spectra of MnII(acac)2 and MnIII(acac)3 complexes in solution,
      utilizing a liquid flatjet for X-ray absorption spectroscopy in transmission
      mode. With this, we derive absolute absorption cross-sections for the L-edge
      transitions with peak magnitudes as large as 12 and 9 Mb for MnII(acac)2 and
      MnIII(acac)3, respectively. We provide insight into the electronic structure with
      ab initio restricted active space calculations of these L-edge transitions,
      reproducing the experimental spectra with excellent agreement in terms of shapes,
      relative energies, and relative intensities for the two complexes. Crystal field
      multiplet theory is used to assign spectral features in terms of the electronic
      structure. Comparison to charge transfer multiplet calculations reveals the
      importance of charge transfer in the core-excited final states. On the basis of
      our experimental observations, we extrapolate the feasibility of 3d transition
      metal L-edge absorption spectroscopy using the liquid flatjet approach in probing
      highly dilute biological solution samples and possible extensions to table-top
      soft X-ray sources.

PMID- 29634282
TI  - Dendrite-Embedded Platinum-Nickel Multiframes as Highly Active and Durable
      Electrocatalyst toward the Oxygen Reduction Reaction.
AB  - Pt-based nanoframe catalysts have been explored extensively due to their superior
      activity toward the oxygen reduction reaction (ORR). Herein, we report the
      synthesis of Pt-Ni multiframes, which exhibit the unique structure of tightly
      fused multiple nanoframes and reinforced by an embedded dendrite. Rapid reduction
      and deposition of Ni atoms on Pt-Ni nanodendrites induce the alloying/dealloying
      of Pt and Ni in the overall nanostructures. After chemical etching of Ni, the
      newly formed dendrite-embedded Pt-Ni multiframes show an electrochemically active
      surface area (ECSA) of 73.4 m2 gPt-1 and a mass ORR activity of 1.51 A mgPt-1 at
      0.93 V, which is 30-fold higher than that of the state-of-the-art Pt/C catalyst.
      We suggest that high ECSA and ORR performances of dendrite-embedded Pt-Ni
      multiframes/C can be attributed to the porous nanostructure and numerous active
      sites exposed on surface grain boundaries and high-indexed facets.

PMID- 29634279
TI  - The Toxicogenome of Hyalella azteca: A Model for Sediment Ecotoxicology and
      Evolutionary Toxicology.
AB  - Hyalella azteca is a cryptic species complex of epibenthic amphipods of interest
      to ecotoxicology and evolutionary biology. It is the primary crustacean used in
      North America for sediment toxicity testing and an emerging model for molecular
      ecotoxicology. To provide molecular resources for sediment quality assessments
      and evolutionary studies, we sequenced, assembled, and annotated the genome of
      the H. azteca U.S. Lab Strain. The genome quality and completeness is comparable
      with other ecotoxicological model species. Through targeted investigation and use
      of gene expression data sets of H. azteca exposed to pesticides, metals, and
      other emerging contaminants, we annotated and characterized the major gene
      families involved in sequestration, detoxification, oxidative stress, and
      toxicant response. Our results revealed gene loss related to light sensing, but a
      large expansion in chemoreceptors, likely underlying sensory shifts necessary in
      their low light habitats. Gene family expansions were also noted for cytochrome
      P450 genes, cuticle proteins, ion transporters, and include recent gene
      duplications in the metal sequestration protein, metallothionein. Mapping of
      differentially expressed transcripts to the genome significantly increased the
      ability to functionally annotate toxicant responsive genes. The H. azteca genome
      will greatly facilitate development of genomic tools for environmental
      assessments and promote an understanding of how evolution shapes toxicological
      pathways with implications for environmental and human health.

PMID- 29634283
TI  - Role of Cellular Metabolism in Pulmonary Diseases.

PMID- 29634285
TI  - ACE2 and pACE2: A Pair of Aces for Pulmonary Arterial Hypertension Treatment?

PMID- 29634284
TI  - Targeting of TAM Receptors Ameliorates Fibrotic Mechanisms in Idiopathic
      Pulmonary Fibrosis.
AB  - RATIONALE: Idiopathic pulmonary fibrosis (IPF) is characterized by aberrant lung
      remodeling, which progressively abolishes lung function in an RTK (receptor
      tyrosine kinase)-dependent manner. Gas6 (growth arrest-specific 6) ligand, Tyro3
      (TYRO3 protein tyrosine kinase 3), and Axl (anexelekto) RTK expression and
      activity are increased in IPF. OBJECTIVES: To determine if targeting these RTK
      pathways would inhibit fibroblast activation and the development of pulmonary
      fibrosis. METHODS: Quantitative genomic, proteomic, and functional analyses were
      used to determine Gas6/TAM (Tyro3, Axl, and Mertk [MER proto-oncogene, tyrosine
      kinase]) RTK expression and activation in tissues and fibroblasts from normal and
      IPF lungs. The profibrotic impact of these RTK pathways were also examined in
      bleomycin-induced pulmonary fibrosis and in SCID/Bg mice that developed pulmonary
      fibrosis after the intravenous administration of primary IPF fibroblasts.
      MEASUREMENTS AND MAIN RESULTS: Gas6, Axl, and Tyro3 were increased in both
      rapidly and slowly progressive IPF compared with normal lung samples and
      fibroblasts. Targeting these pathways with either specific antibodies directed at
      Gas6 or Axl, or with small-molecule TAM inhibitors indicated that the small
      molecule-mediated targeting approach was more efficacious in both in vitro and in
      vivo studies. Specifically, the TAM receptor inhibitor R428 (also known as
      BGB324) significantly inhibited the synthetic, migratory, and proliferative
      properties of IPF fibroblasts compared with the other Gas6/TAM receptor targeting
      agents. Finally, loss of Gas6 expression decreased lung fibrotic responses to
      bleomycin and treatment with R428 inhibited pulmonary fibrosis in humanized
      SCID/Bg mice. CONCLUSIONS: Gas6/TAM receptor activity contributes to the
      activation of pulmonary fibroblasts in IPF, suggesting that targeting this RTK
      pathway might be an effective antifibrotic strategy in this disease.

PMID- 29634287
TI  - Effectiveness of assistive technology in improving the safety of people with
      dementia: a systematic review and meta-analysis.
AB  - OBJECTIVES: Assistive technology (AT) may enable people with dementia to live
      safely at home for longer, preventing care home admission. This systematic review
      assesses the effectiveness of AT in improving the safety of people with dementia
      living in the domestic setting, by searching for randomised controlled trials,
      non-randomised controlled trials and controlled before-after studies which
      compared safety AT with treatment as usual. Measures of safety include care home
      admission; risky behaviours, accidents and falls at home; and numbers of deaths.
      The review updates the safety aspect of Fleming and Sum's 2014 systematic review.
      METHOD: Seven bibliographic databases, the Social Care Institute for Excellence
      website and the Alzheimer's Society website were searched for published and
      unpublished literature between 2011-2016. Search terms related to AT, dementia
      and older people. Common outcomes were meta-analysed. RESULTS: Three randomised
      controlled trials were identified, including 245 people with dementia. No
      significant differences were found between intervention and control groups in
      care home admission (risk ratio 0.85 95% CI [0.37, 1.97]; Z = 0.37; p = 0.71).
      The probability of a fall occurring was 50% lower in the intervention group (risk
      ratio 0.50 95% CI [0.32, 0.78]; Z = 3.03; p = 0.002). One included study found
      that a home safety package containing AT significantly reduced risky behaviour
      and accidents (F(45) = 4.504, p < 0.001). Limitations include the few studies
      found and the inclusion of studies in English only. CONCLUSION: AT's
      effectiveness in decreasing care home admission is inconclusive. However, the AT
      items and packages tested improved safety through reducing falls risk, accidents
      and other risky behaviour.

PMID- 29634290
TI  - Aging, cognition, and the brain: effects of age-related variation in white matter
      integrity on neuropsychological function.
AB  - Alterations in brain structure are viewed as neurobiological indicators which are
      closely tied to cognitive changes in healthy human aging. The current study used
      diffusion tensor imaging (DTI) tractography to investigate the relationship
      between age, brain variation in white matter (WM) integrity, and cognitive
      function. Sixteen younger adults (aged 20-28 years) and 18 healthy older adults
      (aged 60-75 years) underwent DTI scanning and a standardized battery of
      neuropsychological measures. Behaviorally, older adults exhibited poorer
      performance on multiple cognitive measures compared to younger adults. At the
      neural level, the effects of aging on theWM integrity were evident within
      interhemispheric (the anterior portion of corpus callosum) and transverse (the
      right uncinate fasciculus) fibers of the frontal regions, and the cingulum
      angular fibers. Our correlation results showed that age-related WM differentially
      influenced cognitive function, with increased fractional anisotropy values in
      both the anterior corpus callosum and the right cingulum/angular fibers
      positively correlated with performance on the visuospatial task in older adults.
      Moreover, mediation analysis further revealed that the WM tract integrity of the
      frontal interhemspheric fibers was a significant mediator of age-visuospatial
      performance relation in older adults, but not in younger adults. These findings
      support the vulnerability of the frontal WM fibers to normal aging and push
      forward our understanding of cognitive aging by providing a more integrative view
      of the neural basis of linkages among aging, cognition, and brain.

PMID- 29634288
TI  - Depression in type 1 diabetes and risk of dementia.
AB  - OBJECTIVE: Depression afflicts 14% of individuals with type 1 diabetes (T1D).
      Depression is a robust risk factor for dementia but it is unknown if this holds
      true for individuals with T1D, who recently started living to an age conferring
      dementia risk. We examined if depression is a dementia risk factor among elderly
      individuals with T1D. METHODS: 3,742 individuals with T1D age >=50 were followed
      for dementia from 1/1/96-9/30/2015. Depression, dementia, and comorbidities were
      abstracted from electronic medical records. Cox proportional hazard models
      estimated the association between depression and dementia adjusting for
      demographics, glycosylated hemoglobin, severe dysglycemic epidsodes, stroke,
      heart disease, nephropathy, and end stage renal disease. The cumulative incidence
      of dementia by depression was estimated conditional on survival dementia-free to
      age 55. RESULTS: Five percent (N = 182) were diagnosed with dementia and 20% had
      baseline depression. Depression was associated with a 72% increase in dementia
      (fully adjusted HR = 1.72; 95% CI:1.12-2.65). The 25-year cumulative incidence of
      dementia was more than double for those with versus without depression (27% vs.
      12%). CONCLUSIONS: For people with T1D, depression significantly increases
      dementia risk. Given the pervasiveness of depression in T1D, this has major
      implications for successful aging in this population recently living to old age.

PMID- 29634291
TI  - Widowhood, leisure activity engagement, and cognitive function among older
      adults.
AB  - OBJECTIVES: Maintaining cognitive function is an essential aspect of successful
      aging. Widowhood is a salient life transition that can affect older adults'
      cognitive function. Leisure engagement has received increasing attention because
      it is still modifiable in later life to help prevent cognitive decline.
      Nonetheless, limited longitudinal studies have examined how widowhood influences
      cognitive function, and even fewer studies have tested the role of leisure
      activities in this relationship. METHOD: This study delineated the mechanism of
      widowhood, leisure activity engagement, and cognitive function among older adults
      using a national longitudinal dataset, the Health and Retirement Study, and its
      supplementary dataset, the Consumption and Activities Mail Survey, which
      repeatedly measured individuals' leisure activity engagement. RESULTS: Findings
      showed no significant association between widowhood and cognitive function during
      a 4-year period. However, engagement in mental activities moderated the impact of
      widowhood on cognitive function. Specifically, the benefit of mental activity
      engagement on cognition was more pronounced among individuals who were recently
      widowed compared to those who were married. This implies a protective role of
      mental activities in the relationship between widowhood and cognitive function.
      CONCLUSION: Interventions with mentally stimulating activities at the community
      level to retain cognition among individuals in early phase widowhoodare
      suggested. Future studies are necessary to explore whether other factors such as
      changes in physical and mental health and intergenerational support from adult
      children during widowhood may further influence this mechanism among widowhood,
      leisure activities, and cognitive function.

PMID- 29634293
TI  - Special issue on fetal alcohol spectrum disorder.

PMID- 29634294
TI  - Academy of Breastfeeding Medicine's 2017 Position Statement on Informal Breast
      Milk Sharing for the Term Healthy Infant.

PMID- 29634295
TI  - Urbanicity of residence and depression among adults 50 years and older in Ghana
      and South Africa: an analysis of the WHO Study on Global AGEing and Adult Health
      (SAGE).
AB  - OBJECTIVES: As the primary cause of disability worldwide, depression is a
      significant contributor to global morbidity and mortality and often
      disproportionately affects older adults. Several studies have demonstrated a link
      between urban residence and depression, but few studies have examined this
      association among older adult populations, and even fewer have studied it within
      an African context. Given that African societies are aging and urbanizing at
      rapid rates, this study aimed to assess the relationship between urbanicity and
      depression within older adult populations in two African countries. METHOD: Data
      were drawn from the Ghana and South Africa samples of the World Health
      Organization Study on Global AGEing and Adult Health (SAGE) wave 1 (2007-2008).
      Depression over the past 12 months was measured using self-reported treatment and
      depressive symptoms based on ICD-10 criteria in 4209 Ghanaian and 3148 South
      African adults aged 50 years and older residing in their current location for
      over one year. RESULTS: The 12-month prevalence of depression was 7.5% and 4.0%
      in Ghana and South Africa, respectively; 41.1% and 65.6%, respectively, lived in
      urban areas. Comparing urban to rural residents, the adjusted odds ratio (OR) for
      depression in multivariable analysis was 1.13 (95% CI: 0.71-1.79) in South Africa
      and 0.85 (95% CI: 0.55-1.31) in Ghana. CONCLUSION: Results do not support a
      significant urban-rural difference in 12-month depression among Ghanaian or South
      African SAGE participants. Mental health resources in rural areas should
      therefore be enhanced in these countries for more equitable distributions between
      the two settings given similar need.

PMID- 29634296
TI  - Information for Readers.

PMID- 29634297
TI  - Use of Dehydrated Human Amnion/Chorion Membrane Allografts in More Than 100
      Patients with Six Major Types of Refractory Nonhealing Wounds.
AB  - BACKGROUND: Biochemical properties of the amniotic membrane help modulate
      inflammation and enhance soft-tissue healing. In controlled trials, the efficacy
      of dehydrated human amnion/chorion membrane (dHACM) allografts has been
      established. Our purpose is to describe our experience with using dHACM to treat
      nonhealing wounds of various etiologies. METHODS: We conducted a retrospective
      review of deidentified data from 117 consecutive patients treated in an
      outpatient clinic with dHACM allografts with wounds of various etiologies over 2
      years. The decision to use advanced wound-care treatments is based on rate of
      healing observed after initiation of standard wound care and patient risk
      factors. Eligibility for treatments such as amniotic membrane allografts includes
      wounds without 50% reduction after 4 weeks, or earlier in patients deemed to be
      at high risk for nonhealing or with a history of chronic wounds. In micronized or
      sheet formulation, dHACM is applied to the wound weekly after sharp/mechanical
      debridement as necessary, and wound-care practices appropriate for wound type and
      location are continued. RESULTS: Thirty-four percent of allograft recipients had
      diabetic foot ulcers, 25% had venous leg ulcers, 20% had surgical wounds, 14% had
      pressure ulcers, 6% had ischemic wounds, and 2% had traumatic wounds. Complete
      healing occurred in 91.1% of treated patients, with a mean +/- SD number of
      weekly applications per healed wound of 5.1 +/- 4.2. CONCLUSIONS: In addition to
      wounds of diabetic origin, dHACM can significantly expedite healing in refractory
      wounds of varying etiologies.

PMID- 29634298
TI  - Effectiveness of Diagnosis and Treatment of Spiral Fracture of the Distal Third
      of the Tibia Combined with Posterior Malleolus Fracture A Series of Ten Cases.
AB  - BACKGROUND: Spiral fractures of the tibia are often the result of torsion trauma.
      In clinical practice, this type of fracture is frequently complicated by
      posterior malleolus fractures. This study aimed to observe the effectiveness of
      diagnosis and treatment of these fractures in a single hospital in China.
      Posterior malleolus fractures are sometimes occult, occurring alongside spiral
      fractures of the distal third of the tibia; posttraumatic arthritis can result if
      they are missed. METHODS: This study includes 128 consecutive patients with tibia
      fractures between May 1, 2008, and April 30, 2012. Patients in the early study
      period underwent radiography only, and subsequent patients underwent both
      radiography and computed tomography (CT). The causes of the fractures were
      evaluated. Intramedullar nailing was performed for the tibia fractures.
      Percutaneous cannulated screw fixation was used for the posterior malleolus
      fractures. Patients were followed up for a minimum of 3 months. RESULTS: Twenty
      eight patients had spiral fractures of the mid-distal third of the tibia. Ten of
      the 28 patients were complicated by posterior malleolus fractures. Diagnosis was
      initially missed in one early patient who underwent radiography only. Three cases
      of posterior malleolus fractures were identified by radiography. A CT was
      performed in all ten patients and showed that approximately 25% to 50% of the
      ankle joint surface of posterior malleolus fractures was involved. One early
      diagnosis was missed that had a displaced posterior malleolus fracture after
      intramedullary nailing. Using CT as the gold standard, radiography had
      sensitivity of 33.3%, specificity of 100.0%, positive predictive value of 100%,
      and negative predictive value of 73.9%. All correctly diagnosed patients healed
      well, without ankle pain. CONCLUSIONS: Computed tomography helped identify most
      posterior malleolus fractures, and radiography alone might miss it.
      Intramedullary nailing and posterior malleolus screw fixation were
      straightforward and effective treatments.

PMID- 29634299
TI  - The Ring Verruca Plantaris in Cantharidin Use A Case Report.
AB  - Verrucae (warts) are the most common viral infections of the skin, affecting 7%
      to 10% of the general population. Typically caused by human papillomavirus type
      1, plantar warts manifest as benign proliferation of the epithelial cells on the
      feet. It has been cited that up to one-third of nongenital warts become
      recalcitrant, and biopsy is often required to confirm diagnosis and direct
      appropriate treatment. These treatments can vary from various types of oral
      medications, acids, ablative modalities, and injections. In this article, we
      present a case of a recalcitrant plantar wart that appeared to circumferentially
      spread from the initial site after first-line treatment and presumed resolution
      with the product cantharidin. The development of ring warts is a known
      complication associated with cantharidin use, with little described rationale to
      the presentation.

PMID- 29634300
TI  - Lipofibromatous Hamartoma of the Plantar Nerve An Extremely Rare Localization.
AB  - Lipofibromatous hamartoma (LFH) is a rare, benign, tumor-like soft-tissue lesion
      that affects the peripheral nerves and forms a palpable neurogenic mass.
      Lipofibromatous hamartoma is associated with pain and sensory and/or motor
      deficits in the area of innervation of the affected nerve. This report describes
      a rare case of LFH of the plantar nerve. A 48-year-old woman presented to our
      outpatient orthopedic clinic with pain and a burning sensation on her left foot.
      The patient had a history of Morton's neuroma and had undergone a tarsal tunnel
      operation 2 years earlier at another center. None of her symptoms was alleviated
      by two previous operations. Magnetic resonance imaging with contrast revealed
      tenosynovitis of the flexor hallucis longus tendon and signal changes at deep
      tissue planes of the foot at the levels of the second and third toes, on the
      dorsal site and subcutaneous soft-tissue planes, suggesting edema and Morton's
      neuroma. The lesion was excised under spinal anesthesia, and histopathologic
      examination of the specimen revealed a diagnosis of LFH. The patient was
      discharged without any symptoms and her foot was normal at 8-month outpatient
      follow-up, with no indications of postoperative complications and/or recurrence.

PMID- 29634301
TI  - Measurement of Toe-Brachial Indices in People with Subnormal Toe Pressures
      Complexities and Revelations.
AB  - BACKGROUND: Insufficient information exists about the nature of toe-brachial
      indices (TBIs) and how best to obtain them, yet their validity may be
      particularly important for the identification and management of peripheral artery
      disease and cardiovascular disease risk. We explore ways in which valid TBI
      measurements might be obtained. METHODS: The TBI data were recorded from 97
      people with subnormal toe pressures. Most people provided three TBI readings from
      each foot on six different occasions over a 6-month period. The foot with the
      lower baseline TBI was noted. RESULTS: For most people, only small
      inconsistencies existed among the three readings taken from each foot on a single
      occasion, and there were no consistent differences based on sequence. However,
      for some people there were noticeable and unsystematic differences among the
      measures. Selecting any specific one of the three readings based on its
      sequential position, or averaging specific readings, did not yield TBIs that were
      unequivocally typical for a person, and taking the lowest reading of each set
      seemed to offer the most expedient solution in this context. That permitted
      baseline descriptive statistics to be produced for both the higher and lower
      pressure feet, between which there was a statistically significant TBI
      difference. CONCLUSIONS: Accurate and consistent TBI readings cannot be assumed
      for people with subnormal toe pressures, and taking only a single reading or
      indiscriminately averaging readings seems inadvisable. Two readings and, if they
      are discrepant, additional readings, are recommended for each foot, ideally on
      several occasions, and careful consideration should be given to determine the
      most representative reading for each foot. Cuff sizes and other sources of
      inaccuracy or distortion should not be ignored, and standardized protocols for
      obtaining TBIs are recommended.

PMID- 29634302
TI  - Differences in Faculty and Standardized Patient Scores on Professionalism for
      Second-Year Podiatric Medical Students During a Standardized Simulated Patient
      Encounter.
AB  - BACKGROUND: This study examined the differences between faculty and trained
      standardized patient (SP) evaluations on student professionalism during a second
      year podiatric medicine standardized simulated patient encounter. METHODS: Forty
      nine second-year podiatric medicine students were evaluated for their
      professionalism behavior. Eleven SPs performed an assessment in real-time, and
      one faculty member performed a secondary assessment after observing a videotape
      of the encounter. Five domains were chosen for evaluation from a validated
      professionalism assessment tool. RESULTS: Significant differences were identified
      in the professionalism domains of "build a relationship" ( P = .008), "gather
      information" ( P = .001), and share information ( P = .002), where the faculty
      scored the students higher than the SP for 24.5%, 18.9%, and 26.5% of the cases,
      respectively. In addition, the faculty scores were higher than the SP scores in
      all of the "gather information" subdomains; however, the difference in scores was
      significant only in the "question appropriately" ( P = .001) and "listen and
      clarify" ( P = .003) subdomains. CONCLUSIONS: This study showed that
      professionalism scores for second-year podiatric medical students during a
      simulated patient encounter varied significantly between faculty and SPs. Further
      consideration needs to be given to determine the source of these differences.

PMID- 29634303
TI  - Diffuse Pigmented Villonodular Synovitis Around the Ankle.
AB  - BACKGROUND: Pigmented villonodular synovitis (PVNS) is a rare disorder around the
      ankle joint. The optimal treatment for diffuse-type PVNS is still controversial
      because of the high incidence of recurrence. We present the clinical features of
      our patients and review the current diagnostic and treatment modalities. METHODS:
      Five patients with PVNS located around the ankle were surgically treated. In
      three patients, diffuse PVNS arose from the ankle joint, and in the other two it
      arose from the calcaneocuboid and intercuneiform joints. The average follow-up
      time after surgery was 2.9 years (range, 2-4.6 years). RESULTS: The average time
      between onset of pain and diagnosis of PVNS was 6.4 years (range, 4-10 years).
      Arthrotomic tumor resection was performed in all of the patients. In the three
      patients with ankle joint PVNS, both medial and lateral approaches were used. One
      patient experienced mild infection at the surgical site, but this healed
      conservatively. No tumor recurrences had occurred after minimum follow-up of 2
      years, although mild pain persisted in the three patients with ankle PVNS.
      CONCLUSIONS: Diagnosis of diffuse PVNS is frequently delayed due to vague
      symptoms and variable growth patterns. Orthopedic clinicians should be aware of
      the existence of this lesion, and it should be suspected in patients with
      persistent ankle swelling. To prevent tumor recurrence, accurate evaluation of
      tumor location and careful operative planning are mandatory. A combined surgical
      approach involving medial and lateral incision is necessary to expose the entire
      joint cavity.

PMID- 29634304
TI  - Acrokeratoelastoidosis of the Foot with Clinical, Dermoscopic, Ultrasonographic,
      and Histopathologic Correlation.
AB  - Acrokeratoelastoidosis (AKE) is a rare form of focal acral keratoderma of unknown
      cause that typically begins during childhood and manifests with multiple, small,
      hyperkeratotic papules located over the lateral margins of the hands and feet.
      The purpose of this article is to report a pediatric case of AKE with
      dermoscopic, sonographic, and histopathologic descriptions, contributing to the
      awareness of this clinical diagnosis. We describe a 7-year-old girl with
      nonpainful yellowish papules on the lateral and medial aspects of both feet.
      Dermoscopy showed yellowish, structureless, linear areas. The sonographic
      appearance was suggestive of benignancy and ruled out the presence of piezogenic
      pedal papules and granulomas. Histopathology was consistent with AKE, showing
      acral skin with hyperorthokeratosis, hypergranulosis, and elastorrhexis in the
      reticular dermis. Acrokeratoelastoidosis may be difficult to recognize clinically
      because of its resemblance to other focal acral keratodermas. Color Doppler
      ultrasound can be a useful noninvasive tool for diagnosis and can confirm its
      benign appearance, although histopathology confirms the definitive diagnosis. To
      date, the dermoscopic description and ultrasound morphology of AKE have not been
      reported.

PMID- 29634305
TI  - Teaching of Manual Clinical Skills in Podiatric Medicine Theory and
      Recommendations.
AB  - In the podiatric medicine profession, there are a variety of manual tasks that
      require precision and skill beyond what would be usually expected in everyday
      living. It is the expectation of employers, regulatory bodies, and the public
      that graduating podiatric physicians sufficiently meet certain minimum
      competencies for that profession, including those for manual skills. However,
      teaching and evaluation methods seem to be inconsistent between countries,
      institutions, and programs. This may be the consequence of uncertainty regarding
      the safest and most effective methods to do so. A review of available
      international literature pertaining to psychomotor learning across a range of
      health professions was undertaken. As a result of this broad review, we present
      herein the available evidence and make recommendations for the teaching of
      psychomotor skills in the podiatric medicine profession. Specific aspects
      considered important include methods of teaching, practice, and feedback.

PMID- 29634308
TI  - Retained Wooden Foreign Body in the Second Metatarsal.
AB  - The foot is considered the second most common location for foreign bodies. The
      most common foreign bodies include needles, metal, glass, wood, and plastic.
      Although metallic foreign bodies are readily seen on plain film radiographs,
      radiolucent bodies such as wood are visualized poorly, if at all. Although plain
      radiography is known to be ineffective for demonstrating radiolucent foreign
      bodies, it is often the first imaging modality used. In such cases, complete
      surgical extraction cannot be guaranteed, and other imaging modalities should be
      considered. We present a case of a retained toothpick of the second metatarsal in
      a young male patient who presented with pain in the right foot of a few weeks'
      duration. Plain radiography showed an oval cyst at the base of the second
      metatarsal of the right foot. Magnetic resonance imaging revealed a toothpick
      penetrating the second metatarsal. The patient recalled stepping on a toothpick 8
      years previously. Surgical exploration revealed a 2-cm toothpick embedded inside
      the second metatarsal.

PMID- 29634309
TI  - Assessment of the Efficacy of Extracorporeal Shockwave Therapy for Plantar
      Fasciitis with Magnetic Resonance Imaging Findings.
AB  - BACKGROUND: Extracorporeal shockwave therapy (ESWT) has recently been used as a
      new treatment modality for plantar fasciitis. We aimed to determine the efficacy
      of ESWT by magnetic resonance imaging (MRI) findings. METHODS: Thirty patients
      with plantar fasciitis who had received no treatment for 6 months were included.
      Extracorporeal shockwave therapy was applied once a week for a total of three
      sessions (frequency of 12-15 Hz, 2-3 bars, and 2,500 pulses). All of the patients
      were assessed with the visual analog scale, a 6-point evaluation scale, the Foot
      and Ankle Outcome Score (FAOS), and MRI findings before and 3 months after ESWT.
      Visual analog scale scores were used in determining the pain level of patients in
      the morning, during activity, and at rest. Foot and ankle-related problems were
      evaluated with the FAOS. RESULTS: The duration of painless walking according to
      the 6-point rating scale, the FAOS, and pain showed significant improvements
      after ESWT ( P < .05). Significant decreases in MRI findings, including
      thickening of the plantar fascia, soft-tissue edema, and bone marrow edema, were
      observed after treatment ( P < .05). CONCLUSIONS: Extracorporeal shockwave
      therapy is a safe and effective treatment that yields favorable results in
      improvement of pain and function for plantar fasciitis. An MRI is useful for
      determining response to ESWT for these patients.

PMID- 29634310
TI  - A Survey of Patient Care Handoff and Sign-Out Practices Among Podiatric Surgical
      Residency Programs.
AB  - BACKGROUND: A patient "handoff," or the "sign-out" process, is an episode during
      which the responsibility of a patient transitions from one health-care provider
      to another. These are important events that affect patient safety, particularly
      because a significant proportion of adverse events have been associated with a
      relative lack of physician communication. The objective of this investigation was
      to survey podiatric surgical residency programs with respect to patient care
      handoff and sign-out practices. METHODS: A survey was initially developed and
      subsequently administered to the chief residents of 40 Council on Podiatric
      Medical Education-approved podiatric surgical residency programs attempting to
      elucidate patient care handoff protocols and procedures and on-call practices.
      RESULTS: Although it was most common for patient care handoffs to occur in person
      (60.0%), programs also reported that handoffs regularly occurred by telephone
      (52.5%) and with no direct personal communication whatsoever other than the
      electronic passing of information (50.0%). In fact, 27.5% of programs reported
      that their most common means of patient care handoff was without direct resident
      communication and was instead purely electronic. We observed that few residents
      reported receiving formal education or assessment/feedback (17.5%) regarding
      their handoff proficiency, and only 5.0% of programs reported that attending
      physicians regularly took part in the handoff/sign-out process. Although most
      programs felt that their sign-out practices were safe and effective, 67.5% also
      believed that their process could be improved. CONCLUSIONS: These results provide
      unique information on a potentially underappreciated aspect of podiatric medical
      education and might point to some common deficiencies regarding the development
      of interprofessional communication within our profession during residency
      training.

PMID- 29634312
TI  - HDAC3 inhibition in diabetic mice may activate Nrf2 preventing diabetes-induced
      liver damage and FGF21 synthesis and secretion leading to aortic protection.
AB  - Vascular complications are common pathologies associated with type 1 diabetes. In
      recent years, histone deacetylation enzyme (HDAC) inhibitors have been shown to
      be successful in preventing atherosclerosis. To investigate the mechanism for
      HDAC3 inhibition in preventing diabetic aortic pathologies, male OVE26 type 1
      diabetic mice and age-matched wild-type (FVB) mice were given the HDAC3-specific
      inhibitor RGFP-966 or vehicle for 3 mo. These mice were then euthanized
      immediately or maintained for an additional 3 mo without treatment. Levels of
      aortic inflammation and fibrosis and plasma and fibroblast growth factor 21
      (FGF21) levels were determined. Because the liver is the major organ for FGF21
      synthesis in diabetic animals, the effects of HDAC3 inhibition on hepatic FGF21
      synthesis were examined. Additionally, hepatic miR-200a and kelch-like ECH
      associated protein 1 (Keap1) expression and nuclear factor erythroid 2-related
      factor 2 (Nrf2) nuclear translocation were measured. HDAC3 inhibition
      significantly reduced aortic fibrosis and inflammation in OVE26 mice at both 3
      and 6 mo. Plasma FGF21 levels were significantly higher in RGFP-966-treated OVE26
      mice compared with vehicle-treated mice at both time points. It also
      significantly reduced hepatic pathologies associated with diabetes, accompanied
      by increased FGF21 mRNA and protein expression. HDAC3 inhibition also increased
      miR-200a expression, reduced Keap1 protein levels, and increased Nrf2 nuclear
      translocation with an upregulation of antioxidant gene and FGF21 transcription.
      Our results support a model where HDAC3 inhibition may promote Nrf2 activity by
      increasing miR-200a expression with a concomitant decrease in Keap1 to preserve
      hepatic FGF21 synthesis. The preservation of hepatic FGF21 synthesis ultimately
      leads to a reduction in diabetes-induced aorta pathologies.

PMID- 29634311
TI  - Cysteine- and glycine-rich protein 3 regulates glucose homeostasis in skeletal
      muscle.
AB  - Skeletal muscle is the major site of postprandial peripheral glucose uptake, but
      in obesity-induced insulin-resistant states insulin-stimulated glucose disposal
      is markedly impaired. Despite the importance of skeletal muscle in regulating
      glucose homeostasis, the specific transcriptional changes associated with insulin
      sensitive vs. -resistant states in muscle remain to be fully elucidated. Herein,
      using an RNA-seq approach we identified 20 genes differentially expressed in an
      insulin-resistant state in skeletal muscle, including cysteine- and glycine-rich
      protein 3 ( Csrp3), which was highly expressed in insulin-sensitive conditions
      but significantly reduced in the insulin-resistant state. CSRP3 has diverse
      functional roles including transcriptional regulation, signal transduction, and
      cytoskeletal organization, but its role in glucose homeostasis has yet to be
      explored. Thus, we investigated the role of CSRP3 in the development of obesity
      induced insulin resistance in vivo. High-fat diet-fed CSRP3 knockout (KO) mice
      developed impaired glucose tolerance and insulin resistance as well as increased
      inflammation in skeletal muscle compared with wild-type (WT) mice. CSRP3-KO mice
      had significantly impaired insulin signaling, decreased GLUT4 translocation to
      the plasma membrane, and enhanced levels of phospho-PKCalpha in muscle, which all
      contributed to reduced insulin-stimulated glucose disposal in muscle in HFD-fed
      KO mice compared with WT mice. CSRP3 is a highly inducible protein and its
      expression is acutely increased after fasting. After 24h fasting, glucose
      tolerance was significantly improved in WT mice, but this effect was blunted in
      CSRP3-KO mice. In summary, we identify a novel role for Csrp3 expression in
      skeletal muscle in the development of obesity-induced insulin resistance.

PMID- 29634313
TI  - NAD+-dependent deacetylase SIRT3 in adipocytes is dispensable for maintaining
      normal adipose tissue mitochondrial function and whole body metabolism.
AB  - Mitochondrial dysfunction in adipose tissue is involved in the pathophysiology of
      obesity-induced systemic metabolic complications, such as type 2 diabetes,
      insulin resistance, and dyslipidemia. However, the mechanisms responsible for
      obesity-induced adipose tissue mitochondrial dysfunction are not clear. The aim
      of present study was to test the hypothesis that nicotinamide adenine
      dinucleotide (NAD+)-dependent deacetylase sirtuin-3 (SIRT3) in adipocytes plays a
      critical role in adipose tissue mitochondrial biology and obesity. We first
      measured adipose tissue SIRT3 expression in obese and lean mice. Next, adipocyte
      specific mitochondrial Sirt3 knockout (AMiSKO) mice were generated and
      metabolically characterized. We evaluated glucose and lipid metabolism in adult
      mice fed either a regular-chow diet or high-fat diet (HFD) and in aged mice. We
      also determined the effects of Sirt3 deletion on adipose tissue metabolism and
      mitochondrial biology. Supporting our hypothesis, obese mice had decreased SIRT3
      gene and protein expression in adipose tissue. However, despite successful
      knockout of SIRT3, AMiSKO mice had normal glucose and lipid metabolism and did
      not change metabolic responses to HFD-feeding and aging. In addition, loss of
      SIRT3 had no major impact on putative SIRT3 targets, key metabolic pathways, and
      mitochondrial function in white and brown adipose tissue. Collectively, these
      findings suggest that adipocyte SIRT3 is dispensable for maintaining normal
      adipose tissue mitochondrial function and whole body metabolism. Contrary to our
      hypothesis, loss of SIRT3 function in adipocytes is unlikely to contribute to the
      pathophysiology of obesity-induced metabolic complications.

PMID- 29634314
TI  - Pioglitazone improves hepatic mitochondrial function in a mouse model of
      nonalcoholic steatohepatitis.
AB  - Pioglitazone is effective in improving insulin resistance and liver histology in
      patients with nonalcoholic steatohepatitis (NASH). Because dysfunctional
      mitochondrial metabolism is a central feature of NASH, we hypothesized that an
      important target of pioglitazone would be alleviating mitochondrial oxidative
      dysfunction. To this end, we studied hepatic mitochondrial metabolism in mice fed
      high-fructose high-transfat diet (TFD) supplemented with pioglitazone for 20 wk,
      using nuclear magnetic resonance-based 13C isotopomer analysis. Pioglitazone
      improved whole body and adipose insulin sensitivity in TFD-fed mice. Furthermore,
      pioglitazone reduced intrahepatic triglyceride content and fed plasma ketones and
      hepatic TCA cycle flux, anaplerosis, and pyruvate cycling in mice with NASH. This
      was associated with a marked reduction in most intrahepatic diacylglycerol
      classes and, to a lesser extent, some ceramide species (C22:1, C23:0).
      Considering the cross-talk between mitochondrial function and branched-chain
      amino acid (BCAA) metabolism, pioglitazone's impact on plasma BCAA profile was
      determined in a cohort of human subjects. Pioglitazone improved the plasma BCAA
      concentration profile in patients with NASH. This appeared to be related to an
      improvement in BCAA degradation in multiple tissues. These results provide
      evidence that pioglitazone-induced changes in NASH are related to improvements in
      hepatic mitochondrial oxidative dysfunction and changes in whole body BCAA
      metabolism.

PMID- 29634316
TI  - 2017 Acknowledgment of Reviewers.

PMID- 29634315
TI  - Plasma fatty acid ethanolamides are associated with postprandial triglycerides,
      ApoCIII, and ApoE in humans consuming a high-fructose corn syrup-sweetened
      beverage.
AB  - Epidemiological and clinical research studies have provided ample evidence
      demonstrating that consumption of sugar-sweetened beverages increases risk
      factors involved in the development of obesity, Type 2 diabetes, and
      cardiovascular disease (CVD). Our previous study demonstrated that when compared
      with aspartame (Asp), 2 wk of high-fructose corn syrup (HFCS)-sweetened beverages
      provided at 25% of daily energy requirement was associated with increased body
      weight, postprandial (pp) triglycerides (TG), and fasting and pp CVD risk factors
      in young adults. The fatty acid ethanolamide, anandamide (AEA), and the
      monoacylglycerol, 2-arachidonoyl- sn-glycerol (2-AG), are two primary
      endocannabinoids (ECs) that play a role in regulating food intake, increasing
      adipose storage, and regulating lipid metabolism. Therefore, we measured plasma
      concentrations of ECs and their analogs, oleoylethanolamide (OEA),
      docosahexaenoyl ethanolamide (DHEA), and docosahexaenoyl glycerol (DHG), in
      participants from our previous study who consumed HFCS- or Asp-sweetened
      beverages to determine associations with weight gain and CVD risk factors. Two
      week exposure to either HFCS- or Asp-sweetened beverages resulted in significant
      differences in the changes in fasting levels of OEA and DHEA between groups after
      the testing period. Subjects who consumed Asp, but not HFCS, displayed a
      reduction in AEA, OEA, and DHEA after the testing period. In contrast, there were
      significant positive relationships between AEA, OEA, and DHEA vs. ppTG,
      ppApoCIII, and ppApoE in those consuming HFCS, but not in those consuming Asp.
      Our findings reveal previously unknown associations between circulating ECs and
      EC-related molecules with markers of lipid metabolism and CVD risk after HFCS
      consumption.

PMID- 29634317
TI  - Development of a Time-Resolved Fluorescence Resonance Energy Transfer Ultrahigh
      Throughput Screening Assay for Targeting the NSD3 and MYC Interaction.
AB  - Epigenetic modulators play critical roles in reprogramming of cellular functions,
      emerging as a new class of promising therapeutic targets. Nuclear receptor
      binding SET domain protein 3 (NSD3) is a member of the lysine methyltransferase
      family. Interestingly, the short isoform of NSD3 without the methyltransferase
      fragment, NSD3S, exhibits oncogenic activity in a wide range of cancers. We
      recently showed that NSD3S interacts with MYC, a central regulator of
      tumorigenesis, suggesting a mechanism by which NSD3S regulates cell proliferation
      through engaging MYC. Thus, small molecule inhibitors of the NSD3S/MYC
      interaction will be valuable tools for understanding the function of NSD3 in
      tumorigenesis for potential cancer therapeutic discovery. Here we report the
      development of a cell lysate-based time-resolved fluorescence resonance energy
      transfer (TR-FRET) assay in an ultrahigh-throughput screening (uHTS) format to
      monitor the interaction of NSD3S with MYC. In our TR-FRET assay, anti-Flag
      terbium and anti-glutathione S-transferase (GST)-d2, a paired fluorophores, were
      used to indirectly label Flag-tagged NSD3 and GST-MYC in HEK293T cell lysates.
      This TR-FRET assay is robust in a 1,536-well uHTS format, with signal-to
      background >8 and a Z' factor >0.7. A pilot screening with the Spectrum library
      of 2,000 compounds identified several positive hits. One positive compound was
      confirmed to disrupt the NSD3/MYC interaction in an orthogonal protein-protein
      interaction assay. Thus, our optimized uHTS assay could be applied to future
      scaling up of a screening campaign to identify small molecule inhibitors
      targeting the NSD3/MYC interaction.

PMID- 29634318
TI  - Fingerprinting Non-Terran Biosignatures.
AB  - Most strategies for life detection rely upon finding features known to be
      associated with terran life, such as particular classes of molecules. But life
      may be vastly different on other planets and moons, particularly as we expand our
      efforts to explore ocean worlds like Europa and Enceladus. We propose a new
      concept for life detection that harnesses the power of DNA sequencing to yield
      intricate informatics fingerprints, even for life that is not nucleic acid-based.
      The concept is based on the fact that folded nucleic acid structures (aptamers)
      have been shown to be capable of binding a wide variety of compounds, whether
      inorganic, organic, or polymeric, and irrespective of being from a biotic or
      abiotic source. Each nucleic acid sequence can be thought of as a code, and a
      combination of codes as a "fingerprint." Over multiple analytes, the
      "fingerprint" of a non-terran sample can be analyzed by chemometric protocols to
      provide a classifier of molecular patterns and complexity. Ultimately the
      chemometric fingerprints of living systems, which may differ significantly from
      nonliving systems, could provide an empirical, agnostic means of detecting life.
      Because nucleic acids are exponentially amplified by the polymerase chain
      reaction, even very small input signals could be translated into a robust
      readable output. The derived sequences could be identified by a small, portable
      sequencing device or by capture and optical imaging on a DNA microarray. Without
      presupposing any particular molecular framework, this agnostic approach to life
      detection could be used from Mars to the far reaches of the Solar System, all
      within the framework of an instrument drawing little heat and power. Key Words:
      Agnostic biosignatures-Astrobiology-Chemometrics-DNA sequencing-Life detection
      Proximity ligation assay. Astrobiology 18, 915-922.

PMID- 29634319
TI  - Replication of Simulated Prebiotic Amphiphilic Vesicles in a Finite Environment
      Exhibits Complex Behavior That Includes High Progeny Variability and Competition.
AB  - We studied the simulated replication and growth of prebiotic vesicles composed of
      140 phospholipids and cholesterol using our R-GARD (Real Graded Autocatalysis
      Replication Domain) formalism that utilizes currently extant lipids that have
      known rate constants of lipid-vesicle interactions from published experimental
      data. R-GARD normally modifies kinetic parameters of lipid-vesicle interactions
      based on vesicle composition and properties. Our original R-GARD model tracked
      the growth and division of one vesicle at a time in an environment with unlimited
      lipids at a constant concentration. We explore here a modified model where
      vesicles compete for a finite supply of lipids. We observed that vesicles exhibit
      complex behavior including initial fast unrestricted growth, followed by
      intervesicle competition for diminishing resources, then a second growth burst
      driven by better-adapted vesicles, and ending with a final steady state.
      Furthermore, in simulations without kinetic parameter modifications ("invariant
      kinetics"), the initial replication was an order of magnitude slower, and
      vesicles' composition variability at the final steady state was much lower. The
      complex kinetic behavior was not observed either in the previously published R
      GARD simulations or in additional simulations presented here with only one lipid
      component. This demonstrates that both a finite environment (inducing selection)
      and multiple components (providing variation for selection to act upon) are
      crucial for portraying evolution-like behavior. Such properties can improve
      survival in a changing environment by increasing the ability of early
      protocellular entities to respond to rapid environmental fluctuations likely
      present during abiogenesis both on Earth and possibly on other planets. This in
      silico simulation predicts that a relatively simple in vitro chemical system
      containing only lipid molecules might exhibit properties that are relevant to
      prebiotic processes. Key Words: Phospholipid vesicles-Prebiotic compartments
      Prebiotic vesicle competition-Prebiotic vesicle variability. Astrobiology 18, 419
      430.

PMID- 29634320
TI  - Earth Without Life: A Systems Model of a Global Abiotic Nitrogen Cycle.
AB  - Nitrogen is the major component of Earth's atmosphere and plays important roles
      in biochemistry. Biological systems have evolved a variety of mechanisms for
      fixing and recycling environmental nitrogen sources, which links them tightly
      with terrestrial nitrogen reservoirs. However, prior to the emergence of biology,
      all nitrogen cycling was abiological, and this cycling may have set the stage for
      the origin of life. It is of interest to understand how nitrogen cycling would
      proceed on terrestrial planets with comparable geodynamic activity to Earth, but
      on which life does not arise. We constructed a kinetic mass-flux model of
      nitrogen cycling in its various major chemical forms (e.g., N2, reduced (NHx) and
      oxidized (NOx) species) between major planetary reservoirs (the atmosphere,
      oceans, crust, and mantle) and included inputs from space. The total amount of
      nitrogen species that can be accommodated in each reservoir, and the ways in
      which fluxes and reservoir sizes may have changed over time in the absence of
      biology, are explored. Given a partition of volcanism between arc and hotspot
      types similar to the modern ones, our global nitrogen cycling model predicts a
      significant increase in oceanic nitrogen content over time, mostly as NHx, while
      atmospheric N2 content could be lower than today. The transport timescales
      between reservoirs are fast compared to the evolution of the environment; thus
      atmospheric composition is tightly linked to surface and interior processes. Key
      Words: Nitrogen cycle-Abiotic-Planetology-Astrobiology. Astrobiology 18, 897-914.

PMID- 29634321
TI  - Sparse Graphical Models for Functional Connectivity Networks: Best Methods and
      the Autocorrelation Issue.
AB  - Sparse graphical models are frequently used to explore both static and dynamic
      functional brain networks from neuroimaging data. However, the practical
      performance of the models has not been studied in detail for brain networks. In
      this work, we have two objectives. First, we compare several sparse graphical
      model estimation procedures and several selection criteria under various
      experimental settings, such as different dimensions, sample sizes, types of data,
      and sparsity levels of the true model structures. We discuss in detail the
      superiority and deficiency of each combination. Second, in the same simulation
      study, we show the impact of autocorrelation and whitening on the estimation of
      functional brain networks. We apply the methods to a resting-state functional
      magnetic resonance imaging (fMRI) data set. Our results show that the best sparse
      graphical model, in terms of detection of true connections and having few false
      positive connections, is the smoothly clipped absolute deviation (SCAD)
      estimating method in combination with the Bayesian information criterion (BIC)
      and cross-validation (CV) selection method. In addition, the presence of
      autocorrelation in the data adversely affects the estimation of networks but can
      be helped by using the CV selection method. These results question the validity
      of a number of fMRI studies where inferior graphical model techniques have been
      used to estimate brain networks.

PMID- 29634323
TI  - Individual Identification Using the Functional Brain Fingerprint Detected by the
      Recurrent Neural Network.
AB  - Individual identification based on brain function has gained traction in
      literature. Investigating individual differences in brain function can provide
      additional insights into the brain. In this work, we introduce a recurrent neural
      network-based model for identifying individuals based on only a short segment of
      resting-state functional magnetic resonance imaging data. In addition, we
      demonstrate how the global signal and differences in atlases affect individual
      identifiability. Furthermore, we investigate neural network features that exhibit
      the uniqueness of each individual. The results indicate that our model is able to
      identify individuals based on neural features and provides additional information
      regarding brain dynamics.

PMID- 29634322
TI  - Increased Small-World Network Topology Following Deployment-Acquired Traumatic
      Brain Injury Associated with the Development of Post-Traumatic Stress Disorder.
AB  - Cross-sectional and longitudinal studies in active duty and veteran cohorts have
      both demonstrated that deployment-acquired traumatic brain injury (TBI) is an
      independent risk factor for developing post-traumatic stress disorder (PTSD),
      beyond confounds such as combat exposure, physical injury, predeployment TBI, and
      pre-deployment psychiatric symptoms. This study investigated how resting-state
      brain networks differ between individuals who developed PTSD and those who did
      not following deployment-acquired TBI. Participants included postdeployment
      veterans with deployment-acquired TBI history both with and without current PTSD
      diagnosis. Graph metrics, including small-worldness, clustering coefficient, and
      modularity, were calculated from individually constructed whole-brain networks
      based on 5-min eyes-open resting-state magnetoencephalography (MEG) recordings.
      Analyses were adjusted for age and premorbid IQ. Results demonstrated that
      participants with current PTSD displayed higher levels of small-worldness,
      F(1,12) = 5.364, p < 0.039, partial eta squared = 0.309, and Cohen's d = 0.972,
      and clustering coefficient, F(1, 12) = 12.204, p < 0.004, partial eta squared =
      0.504, and Cohen's d = 0.905, than participants without current PTSD. There were
      no between-group differences in modularity or the number of modules present.
      These findings are consistent with a hyperconnectivity hypothesis of the effect
      of TBI history on functional networks rather than a disconnection hypothesis,
      demonstrating increased levels of clustering coefficient rather than a decrease
      as might be expected; however, these results do not account for potential changes
      in brain structure. These results demonstrate the potential pathological sequelae
      of changes in functional brain networks following deployment-acquired TBI and
      represent potential neurobiological changes associated with deployment-acquired
      TBI that may increase the risk of subsequently developing PTSD.

PMID- 29634324
TI  - Job titles need to reflect modern times and go gender neutral.
AB  - The chance to update nursing and midwifery titles can not only help streamline
      the confusing array of roles, but ensure that trusts employ bona fide
      registrants, suggests Sam Foster, Chief Nurse, Oxford University Hospitals.

PMID- 29634325
TI  - Nursing is battered and bruised: but now is the time to fight back.

PMID- 29634326
TI  - Capacity to make decisions: providing the relevant information.
AB  - Richard Griffith, Senior Lecturer in Health Law at Swansea University, discusses
      the nurse's duty in relation to assessing the decision-making capacity of
      patients.

PMID- 29634327
TI  - Nursing Now: nurses at the heart of the challenge to improve global health.
AB  - Elizabeth Rosser, Acting Executive Dean, Bournemouth University, discusses two
      initiatives to promote nursing around the world and make improvements in global
      health.

PMID- 29634328
TI  - Caring for patients with dementia in the acute care setting.
AB  - This article highlights the vulnerability of people with dementia in the acute
      hospital setting, where they are more likely to experience clinical incidents
      such as falls, contract infections and be prescribed neuroleptic drugs. This
      patient group has a significantly longer length of hospital stay and higher
      mortality rate following discharge compared with those without dementia. As many
      as one third are discharged to institutionalised care. The article explores the
      knowledge gap concerning the complexity of caring for a person with dementia and
      highlights factors that can lead to staff detaching themselves from engaging in
      meaningful communication with patients. It also discusses the syndrome of
      'cascade iatrogenesis' in relation to patients' physical and cognitive decline.
      More emphasis needs to be placed on addressing these issues to ensure the safety
      and welfare of people with dementia in hospitals. A case study from the author's
      clinical practice is used to illustrate the issues.

PMID- 29634329
TI  - Could a risk-assessment tool prevent hospital-acquired pneumonia?
AB  - Hospital-acquired pneumonia (HAP) has been shown to be the second most common
      healthcare-acquired infection (HCAI) after urinary tract infection and linked to
      more than half of all deaths from HCAIs. Preventing the infection could
      potentially save many lives. The author therefore proposes that HAP could be
      prevented by the implementation of a risk-assessment tool. A hypothetical risk
      assessment tool is discussed. Several potential risk factors are proposed;
      however, further research into these risk factors and the appropriate weighting
      to give these in developing such a tool is required.

PMID- 29634331
TI  - Failing to fail.

PMID- 29634330
TI  - Is the duty of candour under threat?
AB  - Emeritus Professor Alan Glasper, University of Southampton, dissects the case of
      paediatrician Dr Hadiza Bawa-Garba and registered nurse Isabel Amaro, and how
      their convictions might affect the duty of candour legislation.

PMID- 29634332
TI  - Transforming classroom questioning using emerging technology.
AB  - Classroom questioning is a common teaching and learning strategy in postgraduate
      nurse education. Technologies such as audience response systems (ARS) may offer
      advantage over traditional approaches to classroom questioning. However, despite
      being available since the 1960s, ARSs are still considered novel in many
      postgraduate nurse education classroom settings. This article aims to explicate
      the attitudes of postgraduate nursing students in an Irish academic teaching
      hospital towards classroom questioning (CQ) and the use of ARSs as an alternative
      to traditional CQ techniques. The results of this small-scale study demonstrate
      that ARSs have a role to play in CQ in the postgraduate setting, being regarded
      by students as beneficial to learning, psychological safety and classroom
      interaction.

PMID- 29634333
TI  - A crisis point for mental health care.
AB  - John Tingle, Associate Professor (Teaching and Scholarship), Nottingham Trent
      University, discusses failings in NHS care for highly vulnerable mental health
      patients.

PMID- 29634334
TI  - Antimicrobial resistance: join us for a fresh approach.

PMID- 29634335
TI  - Managing faecal incontinence.

PMID- 29634336
TI  - Differentiation of delirium, dementia and delirium superimposed on dementia in
      the older person.
AB  - Delirium is an acute clinical emergency that requires prompt clinical
      intervention. A predisposing factor for delirium is dementia, and delirium may
      highlight the vulnerability of a patient to developing dementia. However,
      delirium also occurs during an acute illness in patients diagnosed with dementia;
      this is classified as delirium superimposed on dementia. This complex interplay
      of both dementia syndromes and the condition of delirium has been extensively
      studied. However, delirium continues to be under-recognised in the acute setting,
      which impacts negatively on patient outcomes. Nurses are the health professionals
      best placed to recognise a change in a patient's cognitive symptoms, but nurses
      caring for the older person have suggested the identification of and
      differentiation between delirium, dementia and delirium superimposed on dementia
      remains very confusing. A need for further education with supportive guidelines
      and protocols is required to empower nurses caring for an older person to
      verbalise changes in patients' cognitive status in a reliable, robust and
      systematic manner.

PMID- 29634337
TI  - Supporting self-management of asthma through patient education.
AB  - Asthma affects people worldwide. In developed countries 1 in 12 individuals
      suffer from asthma, while in Ireland this ratio is closer to 1 in 10. Managing
      asthma symptoms and triggers reduces the potential exacerbation of asthmatic
      attacks. This article identifies the importance of asthma management, triggers,
      inhaler techniques and self-management for optimal health. Education by nurses
      and health professionals can make a significant contribution to asthma care and
      self-management. The purpose of patient education for self-management of asthma
      is twofold: to raise awareness of effective inhaler technique and to support self
      management of asthma triggers for health and symptom control.

PMID- 29634338
TI  - Incorporating motivational interviewing into rheumatology care.
AB  - Deborah Palmer, Advanced Nurse Practitioner, North Middlesex University Hospital,
      and Yasser El Miedany, Consultant Rheumatologist, discuss ways to close the gap
      between disease control and patient empowerment.

PMID- 29634339
TI  - The effectiveness of alcohol-based gel for hand sanitising in infection control.
AB  - This article aims to evaluate the evidence relating to the effectiveness of
      alcohol-based gel for hand sanitising, or 'handrub', in infection control in
      healthcare settings with particular reference to renal nursing, as this has
      become pertinent due to the increasing reliance on evidence-based practice. There
      is a need to implement better infection control strategies and education, to
      reinforce knowledge among the public, health professionals and those at high risk
      of infection not only in renal nursing, but also in other areas of practice.
      Healthcare-associated infections (HCAIs) put patients' safety at risk, increase
      morbidity and mortality, extend the length of hospital admission and increase the
      cost to the NHS. There is evidence that the prevalence of HCAIs in England can be
      minimised through the use of different infection control measures. For example,
      alcohol-based handrub has been found to be associated with minimising the spread
      of gastrointestinal infections not only in hospital settings, but also in
      childcare centres. In addition, the UK national guidelines recommend regular
      handwashing (implementing the right technique) when hands are visibly dirty and
      hand disinfection with alcohol-based handrub when they are not visibly dirty.
      This should be before, in between and after different healthcare activities are
      performed.

PMID- 29634340
TI  - Differences in Breastfeeding Among Medicaid and Commercially Insured Patients: A
      Retrospective Cohort Study.
AB  - BACKGROUND: While breastfeeding rates have been increasing in the United States,
      they remain below targets set by multiple public health organizations. Lower
      rates are associated with certain demographic groups. We performed a
      retrospective chart review to examine rates of breastfeeding at the time of
      postpartum follow-up in a mixed-race urban cohort. OBJECTIVE: This study was
      conducted to examine the proportion of women who were breastfeeding at 6-8 weeks
      postpartum and to determine if these proportions differed by race and insurance
      status. MATERIALS AND METHODS: We identified women who delivered singleton term
      infants at an urban university hospital between July and December 2013. Self
      reported breastfeeding status at 6-8 weeks postpartum was abstracted for all
      women who completed postpartum follow-up visits. Data were analyzed with logistic
      regression to compare rates of any or exclusive breastfeeding between women with
      Medicaid and private insurance. RESULTS: Charts of 656 women were reviewed; 405
      women completed postpartum follow-up within 8 weeks. The Medicaid population had
      significantly lower rates of breastfeeding even after accounting for interaction
      and confounding by demographic factors (any breastfeeding odd ratio [OR] 0.53,
      confidence interval [CI] 0.04-0.31; exclusive breastfeeding OR 0.48, CI 0.33
      0.85). When stratified by race, white women on Medicaid had the lowest
      probability of breastfeeding of all groups (p < 0.01). CONCLUSIONS: Among
      patients delivering at an urban academic hospital, women on Medicaid were
      significantly less likely to breastfeed than those with private insurance. The
      greatest differential by insurance was seen among white women. Efforts to improve
      breastfeeding should focus on low-income women of all races.

PMID- 29634342
TI  - Calcium Signaling Deficits in Glia and Autophagic Pathways Contributing to
      Neurodegenerative Disease.
AB  - SIGNIFICANCE: Numerous cellular processes and signaling mechanisms have been
      identified that contribute to Alzheimer's disease (AD) pathology; however, a
      comprehensive or unifying pathway that binds together the major disease features
      remains elusive. As an upstream mechanism, altered calcium (Ca2+) signaling is a
      common driving force for many pathophysiological events that emerge during normal
      aging and development of neurodegenerative disease. Recent Advances: Over the
      previous three decades, accumulated evidence has validated the concept that
      intracellular Ca2+ dysregulation is centrally involved in AD pathogenesis,
      including the aggregation of pathogenic beta-amyloid (Abeta) and phospho-tau
      species, synapse loss and dysfunction, cognitive impairment, and neurotoxicity.
      CRITICAL ISSUES: Although neuronal Ca2+ signaling within the cytosol and
      endoplasmic reticulum (ER) has been well studied, other critical central nervous
      system-resident cell types affected by aberrant Ca2+ signaling, such as
      astrocytes and microglia, have not been considered as thoroughly. In addition,
      certain intracellular Ca2+-harboring organelles have been well studied, such as
      the ER and mitochondria; however other critical Ca2+-regulated organelles, such
      as lysosomes and autophagosomes, have only more recently been investigated. In
      this review, we examine Ca2+ dysregulation in microglia and astrocytes, as well
      as key intracellular organelles important for cellular maintenance and protein
      handling. Ca2+ dysregulation within these non-neuronal cells and organelles is
      hypothesized to disrupt the effective clearance of misaggregated proteins and
      cellular signaling pathways needed for memory networks. FUTURE DIRECTIONS:
      Overall, we aim to explore how these disrupted mechanisms could be involved in AD
      pathology and consider their role as potential therapeutic targets. Antioxid.
      Redox Signal. 29, 1158-1175.

PMID- 29634341
TI  - Transflammation: How Innate Immune Activation and Free Radicals Drive Nuclear
      Reprogramming.
AB  - SIGNIFICANCE: Yamanaka and colleagues galvanized the field of stem cell biology
      and regenerative medicine by their generation of induced pluripotent stem cells.
      Evidence is emerging that activation of innate immune signaling is critical for
      efficient reprogramming to pluripotency and for the nuclear reprogramming
      occurring in transdifferentiation. Recent Advances: We have shown that innate
      immune signaling triggers a global change in the expression of epigenetic
      modifiers to enhance DNA accessibility. In this state of epigenetic plasticity,
      overexpression of lineage determination factors, and/or environmental cues and
      paracrine factors, can induce pluripotency, or can direct transdifferentiation to
      another somatic cell lineage. Accumulating evidence reveals that innate immune
      activation triggers the generation of reactive oxygen species and reactive
      nitrogen species, and that these free radicals are required for nuclear
      reprogramming to pluripotency or for transdifferentiation. CRITICAL ISSUES: We
      have discovered a limb of innate immune signaling that regulates DNA
      accessibility, in part, by the action of free radicals to induce post
      translational modification of epigenetic modifiers. FUTURE DIRECTIONS: It is of
      scientific interest and clinical relevance to understand the mechanisms by which
      free radicals influence epigenetic plasticity, and how these mechanisms may be
      therapeutically modulated. Antioxid. Redox Signal. 00, 000-000.

PMID- 29634345
TI  - Identification of an Unfavorable Immune Signature in Advanced Lung Tumors from
      Nrf2-Deficient Mice.
AB  - AIMS: Activation of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2)
      pathway in normal cells inhibits carcinogenesis, whereas constitutive activation
      of Nrf2 in cancer cells promotes tumor growth and chemoresistance. However, the
      effects of Nrf2 activation in immune cells during lung carcinogenesis are poorly
      defined and could either promote or inhibit cancer growth. Our studies were
      designed to evaluate tumor burden and identify immune cell populations in the
      lungs of Nrf2 knockout (KO) versus wild-type (WT) mice challenged with vinyl
      carbamate. RESULTS: Nrf2 KO mice developed lung tumors earlier than the WT mice
      and exhibited more and larger tumors over time, even at late stages. T cell
      populations were lower in the lungs of Nrf2 KO mice, whereas tumor-promoting
      macrophages and myeloid-derived suppressor cells were elevated in the lungs and
      spleen, respectively, of Nrf2 KO mice relative to WT mice. Moreover, 34 immune
      response genes were significantly upregulated in tumors from Nrf2 KO mice,
      especially a series of cytokines (Cxcl1, Csf1, Ccl9, Cxcl12, etc.) and major
      histocompatibility complex antigens that promote tumor growth. INNOVATION: Our
      studies discovered a novel immune signature, characterized by the infiltration of
      tumor-promoting immune cells, elevated cytokines, and increased expression of
      immune response genes in the lungs and tumors of Nrf2 KO mice. A complementary
      profile was also found in lung cancer patients, supporting the clinical
      significance of our findings. CONCLUSION: Overall, our results confirmed a
      protective role for Nrf2 in late-stage carcinogenesis and, unexpectedly, suggest
      that activation of Nrf2 in immune cells may be advantageous for preventing or
      treating lung cancer. Antioxid. Redox Signal.

PMID- 29634346
TI  - Redox Biology in Neurological Function, Dysfunction, and Aging.
AB  - Reduction oxidation (redox) reactions are central to life and when altered, they
      can promote disease progression. In the brain, redox homeostasis is recognized to
      be involved in all aspects of central nervous system (CNS) development, function,
      aging, and disease. Recent studies have uncovered the diverse nature by which
      redox reactions and homeostasis contribute to brain physiology, and when
      dysregulated to pathological consequences. Redox reactions go beyond what is
      commonly described as oxidative stress and involve redox mechanisms linked to
      signaling and metabolism. In contrast to the nonspecific nature of oxidative
      damage, redox signaling involves specific oxidation/reduction reactions that
      regulate a myriad of neurological processes such as neurotransmission,
      homeostasis, and degeneration. This Forum is focused on the role of redox
      metabolism and signaling in the brain. Six review articles from leading
      scientists in the field that appraise the role of redox metabolism and signaling
      in different aspects of brain biology including neurodevelopment,
      neurotransmission, aging, neuroinflammation, neurodegeneration, and neurotoxicity
      are included. An original research article exemplifying these concepts uncovers a
      novel link between oxidative modifications, redox signaling, and
      neurodegeneration. This Forum highlights the recent advances in the field and we
      hope it encourages future research aimed to understand the mechanisms by which
      redox metabolism and signaling regulate CNS physiology and pathophysiology.
      Antioxid. Redox Signal. 28, 1583-1586.

PMID- 29634343
TI  - Dietary and Endocrine Regulation of Endogenous Hydrogen Sulfide Production:
      Implications for Longevity.
AB  - SIGNIFICANCE: Hydrogen sulfide (H2S) at the right concentration is associated
      with numerous health benefits in experimental organisms, ranging from protection
      from ischemia/reperfusion injury to life span extension. Given the considerable
      translation potential, two major strategies have emerged: supplementation of
      exogenous H2S and modulation of endogenous H2S metabolism. Recent Advances:
      Recently, it was reported that hepatic H2S production capacity is increased in
      two of the best-characterized mammalian models of life span extension, dietary
      restriction, and hypopituitary dwarfism, leading to new insights into dietary and
      hormonal regulation of endogenous H2S production together with broader changes in
      sulfur amino acid (SAA) metabolism with implications for DNA methylation and
      redox status. CRITICAL ISSUES: Here, we discuss the role of dietary SAAs and
      growth hormone (GH)/thyroid hormone (TH) signaling in regulation of endogenous
      H2S production largely via repression of H2S generating enzymes cystathionine
      gamma-lyase (CGL) and cystathionine beta-synthase (CBS) on the level of gene
      transcription, as well as reciprocal regulation of GH and TH signaling by H2S
      itself. We also discuss plasticity of CGL and CBS gene expression in response to
      environmental stimuli and the potential of the microbiome to impact overall H2S
      levels. FUTURE DIRECTIONS: The relative contribution of increased H2S to health
      span or lifespan benefits in models of extended longevity remains to be
      determined, as does the mechanism by which such benefits occur. Nonetheless, our
      ability to control H2S levels using exogenous H2S donors or by modifying the
      endogenous H2S production/consumption equilibrium has the potential to improve
      health and increase "shelf-life" across evolutionary boundaries, including our
      own. Antioxid. Redox Signal. 28, 1483-1502.

PMID- 29634347
TI  - Extracellular Vesicles: Mechanisms in Human Health and Disease.
AB  - SIGNIFICANCE: Secreted extracellular vesicles (EVs) are now considered veritable
      entities for diagnosis, prognosis, and therapeutics. These structures are able to
      interact with target cells and modify their phenotype and function. Recent
      Advances: Since composition of EVs depends on the cell type of origin and the
      stimulation that leads to their release, the analysis of EV content remains an
      important input to understand the potential effects of EVs on target cells.
      CRITICAL ISSUES: Here, we review recent data related to the mechanisms involved
      in the formation of EVs and the methods allowing specific EV isolation and
      identification. Also, we analyze the potential use of EVs as biomarkers in
      different pathologies such as diabetes, obesity, atherosclerosis,
      neurodegenerative diseases, and cancer. Besides, their role in these diseases is
      discussed. Finally, we consider EVs enriched in microRNA or drugs as potential
      therapeutic cargo able to deliver desirable information to target cells/tissues.
      FUTURE DIRECTIONS: We underline the importance of the homogenization of the
      parameters of isolation of EVs and their characterization, which allow
      considering EVs as excellent biomarkers for diagnosis and prognosis. Antioxid.
      Redox Signal. 00, 000-000.

PMID- 29634348
TI  - Molecular Mechanisms of Nitric Oxide in Cancer Progression, Signal Transduction,
      and Metabolism.
AB  - SIGNIFICANCE: Cancer is a complex disease, which not only involves the tumor but
      its microenvironment comprising different immune cells as well. Nitric oxide (NO)
      plays specific roles within tumor cells and the microenvironment and determines
      the rate of cancer progression, therapy efficacy, and patient prognosis. Recent
      Advances: Key understanding of the processes leading to dysregulated NO flux
      within the tumor microenvironment over the past decade has provided better
      understanding of the dichotomous role of NO in cancer and its importance in
      shaping the immune landscape. It is becoming increasingly evident that nitric
      oxide synthase 2 (NOS2)-mediated NO/reactive nitrogen oxide species (RNS) are
      heavily involved in cancer progression and metastasis in different types of
      tumor. More recent studies have found that NO from NOS2+ macrophages is required
      for cancer immunotherapy to be effective. CRITICAL ISSUES: NO/RNS, unlike other
      molecules, are unique in their ability to target a plethora of oncogenic pathways
      during cancer progression. In this review, we subcategorize the different levels
      of NO produced by cells and shed light on the context-dependent temporal effects
      on cancer signaling and metabolic shift in the tumor microenvironment. FUTURE
      DIRECTIONS: Understanding the source of NO and its spaciotemporal profile within
      the tumor microenvironment could help improve efficacy of cancer immunotherapies
      by improving tumor infiltration of immune cells for better tumor clearance.
      Antioxid. Redox Signal. 00, 000-000.

PMID- 29634349
TI  - Dl-3-n-Butylphthalide Inhibits NLRP3 Inflammasome and Mitigates Alzheimer's-Like
      Pathology via Nrf2-TXNIP-TrX Axis.
AB  - AIMS: Oxidative stress and neuroinflammation play important roles in the
      pathology of Alzheimer's disease (AD). Thioredoxin-interacting protein (TXNIP),
      an endogenous inhibitor of antioxidant thioredoxin, is suspected to be an
      important modulator of oxidative stress and inflammation. However, the underlying
      mechanism involved in the abnormal homeostasis of TXNIP-thioredoxin (TrX) in AD
      pathogenesis remains unclear. RESULTS: Using the Swedish mutant form of APP
      (APPswe)/PSEN1dE9 transgenic mouse (APP/PS1) and human-derived neuronal cells as
      model systems, we disclosed the impairment of the nuclear factor erythroid 2
      related factor 2 (Nrf2)-TXNIP-TrX signaling in Alzheimer's-like pathology. We
      observed that the immune staining of TXNIP was increased in postmortem AD brain.
      The chronic accumulation of inflammatory mediator in neuronal cells facilitates
      interactions of TXNIP-nucleotide binding oligomerization domain-like receptor
      family, pyrin domain containing 3 (NLRP3) and NLRP3-ASC, which increases beta
      amyloid (Abeta) secretion. The antioxidant Dl-3-n-butylphthalide (Dl-NBP) is
      commonly used for cerebral ischemia treatment. In our study, we elucidated for
      new mechanisms by which Dl-NBP enhanced TrX activity, suppressed TXNIP, and
      ameliorated neuronal apoptosis in the APP/PS1 mouse brains. In human glioblastoma
      A172 cells and neuroblastoma SH-SY5Y cells, we delineated the Dl-NBP-mediated
      signaling pathways by which Dl-NBP-dependent upregulation of Nrf2 mediated the
      reciprocal regulation of reducing proinflammatory cytokine and inhibiting Abeta
      production in the glial and neuronal cells overexpressing APPswe. INNOVATION: Our
      data provide a novel insight into the molecular mechanism that impairments of
      Nrf2-TXNIP-TrX system may be involved in the imbalance of cellular redox
      homeostasis and inflammatory damage in the AD brain. CONCLUSION: Dl-NBP treatment
      could suppress TXNIP-NLRP3 interaction and inhibit NLRP3 inflammasome activation
      via upregulating Nrf2. These findings may provide an instrumental therapeutic
      approach for AD. Antioxid. Redox Signal. 00, 000-000.

PMID- 29634350
TI  - Redox Mechanisms in Neurodegeneration: From Disease Outcomes to Therapeutic
      Opportunities.
AB  - SIGNIFICANCE: Once considered to be mere by-products of metabolism, reactive
      oxygen, nitrogen and sulfur species are now recognized to play important roles in
      diverse cellular processes such as response to pathogens and regulation of
      cellular differentiation. It is becoming increasingly evident that redox
      imbalance can impact several signaling pathways. For instance, disturbances of
      redox regulation in the brain mediate neurodegeneration and alter normal
      cytoprotective responses to stress. Very often small disturbances in redox
      signaling processes, which are reversible, precede damage in neurodegeneration.
      Recent Advances: The identification of redox-regulated processes, such as
      regulation of biochemical pathways involved in the maintenance of redox
      homeostasis in the brain has provided deeper insights into mechanisms of
      neuroprotection and neurodegeneration. Recent studies have also identified
      several post-translational modifications involving reactive cysteine residues,
      such as nitrosylation and sulfhydration, which fine-tune redox regulation. Thus,
      the study of mechanisms via which cell death occurs in several neurodegenerative
      disorders, reveal several similarities and dissimilarities. Here, we review redox
      regulated events that are disrupted in neurodegenerative disorders and whose
      modulation affords therapeutic opportunities. CRITICAL ISSUES: Although
      accumulating evidence suggests that redox imbalance plays a significant role in
      progression of several neurodegenerative diseases, precise understanding of redox
      regulated events is lacking. Probes and methodologies that can precisely detect
      and quantify in vivo levels of reactive oxygen, nitrogen and sulfur species are
      not available. FUTURE DIRECTIONS: Due to the importance of redox control in
      physiologic processes, organisms have evolved multiple pathways to counteract
      redox imbalance and maintain homeostasis. Cells and tissues address stress by
      harnessing an array of both endogenous and exogenous redox active substances.
      Targeting these pathways can help mitigate symptoms associated with
      neurodegeneration and may provide avenues for novel therapeutics. Antioxid. Redox
      Signal. 00, 000-000.

PMID- 29634351
TI  - Ethics of Research Biobanks: Islamic Perspectives.
AB  - Research biobanks can offer great benefits for science and healthcare. However,
      many ethical challenges arise from their use. These challenges have different
      perspectives in Muslim countries when research biobanks are created. We propose
      principles for good practice related to the research biobanks in Islamic
      countries, focusing on issues related to confidentiality, informed consent,
      children's participation, and others. These issues were explored according to
      Islamic fatwas and Usul Al Fiqh, and we provide principles for good practice for
      policy makers involved in the creation of research biobanks, researchers, and
      anyone who has to deal with stored tissue specimens taken from Muslims. The
      actual implementation of the principles will vary according to different
      jurisdictions.

PMID- 29634353
TI  - A global research collaboration on fetal alcohol spectrum disorder.

PMID- 29634354
TI  - Mental health symptoms and verbal fluency in elderly people: Evidence from the
      Spanish longitudinal study of aging.
AB  - OBJECTIVES: Depression and loneliness are highly prevalent in old age. Moreover
      these mental health symptoms adversely affect the verbal fluency of the elderly.
      We examined the relationship between depression and loneliness with verbal
      fluency in people aged 50 years or older. METHOD: Research data were collected
      during the pilot study of the Longitudinal Aging Study in Spain (ELES) in which a
      representative sample of non-institutionalized Spanish older people was assessed.
      Here, the cross-sectional data for 962 participants were analysed using
      hierarchical regressions, controlling for age, education level, overall cognitive
      functioning, social networks and satisfaction with family. RESULTS: Higher levels
      of cognitive functioning were associated with higher verbal fluency. Females
      showed higher levels of phonological fluency. Neither depression nor loneliness
      were significant predictors of phonological fluency but loneliness was a
      significant predictor of semantic fluency. For mild levels of loneliness, the
      rate of decline in semantic fluency slows in the oldest ages. In contrast, for
      severe loneliness the rate of decline in semantic fluency increases in the oldest
      ages. CONCLUSIONS: Depressive symptoms, loneliness and cognitive impairment are
      all prominent in ageing and therefore their impact on ageing needs to be better
      understood. Early detection of loneliness, along with the implementation of
      intervention for individuals diagnosed with loneliness is advisable in order to
      avoid negative repercussions for the verbal fluency of these individuals.

PMID- 29634355
TI  - Evaluation of 99mTc-Labeled Bevacizumab-N-HYNIC Conjugate in Human Ovarian Tumor
      Xenografts.
AB  - AIM: The aim of the present investigation was to examine the suitability of 99mTc
      N-HYNIC-BZMB as a specific vascular endothelial growth factor (VEGF)-targeting
      agent. Bevacizumab is a recombinant humanized monoclonal antibody that inhibits
      VEGF. METHODS: N-hydroxysuccinimide-2-hydrazinonicotinic acid (N-HYNIC) was
      conjugated to BZMB, followed by labeling with 99mTc using N
      [Tris(hydroxymethyl)methyl] glycine (tricine), ethylenediamine-N,N'-diacetic acid
      (EDDA), and nicotinic acid as coligands. 99mTc-labeled BZMB was characterized in
      terms of 99mTcO4, radiocolloids, and labeled N-HYNIC-BZMB using thin-layer
      chromatography and HPLC. Poor metastatic SKOV-3 and high metastatic SKOV-3.ip1
      human ovarian cancer cell lines were used for in vitro binding uptake of 99mTc-N
      HYNIC-BZMB. Biodistribution and scintigraphy accuracy were examined in human
      ovarian tumor xenografts in rats and rabbits. RESULTS: 99mTc-N-HYNIC-BZMB
      prepared by using a mixture of tricine and EDDA demonstrated relatively high
      radiochemical purity (more than 98%). In L-cysteine and serum, it exhibited a
      stable behavior up to 16 hours. In vitro binding uptake indicated that it targets
      high metastatic SKOV-3.ip1 tumors. Biodistribution in human ovarian tumor
      xenografts in rats confirmed a significant uptake in SKOV-3.ip1 tumors (5.69% +/-
      1.86%, 4 hours). Scintigraphic accuracy in human ovarian tumor xenografts in
      rabbits validated its suitability as a high metastatic SKOV-3.ip1 radiotracer.
      CONCLUSION: High radiochemical purity, stability in saline and serum,
      biodistribution, and scintigraphy of 99mTc-N-HYNIC-BZMB in human ovarian tumor
      xenografts in rats and rabbits confirmed its suitability as a potential
      radiotracer for imaging high metastatic SKOV-3.ip1 sites.

PMID- 29634344
TI  - Role of Nicotinamide Adenine Dinucleotide and Related Precursors as Therapeutic
      Targets for Age-Related Degenerative Diseases: Rationale, Biochemistry,
      Pharmacokinetics, and Outcomes.
AB  - SIGNIFICANCE: Nicotinamide adenine dinucleotide (NAD+) is an essential pyridine
      nucleotide that serves as an essential cofactor and substrate for a number of
      critical cellular processes involved in oxidative phosphorylation and ATP
      production, DNA repair, epigenetically modulated gene expression, intracellular
      calcium signaling, and immunological functions. NAD+ depletion may occur in
      response to either excessive DNA damage due to free radical or ultraviolet
      attack, resulting in significant poly(ADP-ribose) polymerase (PARP) activation
      and a high turnover and subsequent depletion of NAD+, and/or chronic immune
      activation and inflammatory cytokine production resulting in accelerated CD38
      activity and decline in NAD+ levels. Recent studies have shown that enhancing
      NAD+ levels can profoundly reduce oxidative cell damage in catabolic tissue,
      including the brain. Therefore, promotion of intracellular NAD+ anabolism
      represents a promising therapeutic strategy for age-associated degenerative
      diseases in general, and is essential to the effective realization of multiple
      benefits of healthy sirtuin activity. The kynurenine pathway represents the de
      novo NAD+ synthesis pathway in mammalian cells. NAD+ can also be produced by the
      NAD+ salvage pathway. Recent Advances: In this review, we describe and discuss
      recent insights regarding the efficacy and benefits of the NAD+ precursors,
      nicotinamide (NAM), nicotinic acid (NA), nicotinamide riboside (NR), and
      nicotinamide mononucleotide (NMN), in attenuating NAD+ decline in degenerative
      disease states and physiological aging. CRITICAL ISSUES: Results obtained in
      recent years have shown that NAD+ precursors can play important protective roles
      in several diseases. However, in some cases, these precursors may vary in their
      ability to enhance NAD+ synthesis via their location in the NAD+ anabolic
      pathway. Increased synthesis of NAD+ promotes protective cell responses, further
      demonstrating that NAD+ is a regulatory molecule associated with several
      biochemical pathways. FUTURE DIRECTIONS: In the next few years, the refinement of
      personalized therapy for the use of NAD+ precursors and improved detection
      methodologies allowing the administration of specific NAD+ precursors in the
      context of patients' NAD+ levels will lead to a better understanding of the
      therapeutic role of NAD+ precursors in human diseases. Antioxid. Redox Signal.
      00, 000-000.

PMID- 29634356
TI  - A Culture-Centered Community-Grounded Approach to Disseminating Health
      Information among African Americans.
AB  - This study highlights the role of local communities in creating culturally rooted
      health information resources based on comparative effectiveness research (CER),
      depicting the role of culture in creating entry points for building community
      grounded communication structures for evidence-based health knowledge. We report
      the results from running a year-long culture-centered campaign that was carried
      out among African American communities in two counties, Lake and Marion County,
      in Indiana addressing basic evidence-based knowledge on four areas of
      cardiovascular disease (CVD). Campaign effectiveness was tested through an
      experimental design with post-test knowledge of CER among African Americans in
      these counties compared to CER knowledge among African Americans in a comparable
      control county (Allen). Our campaign, based on the principles of the culture
      centered approach (CCA), increased community CER knowledge in the experimental
      communities relative to a community that did not receive the culturally centered
      health information campaign. The CCA-based campaign developed by community
      members and distributed through the mass media, community wide channels such as
      health fairs and church meetings, postcards, and face-to-face interventions
      explaining the postcards improved CER knowledge in specific areas (ACE-I/ARBs,
      atrial fibrillation, and renal artery stenosis) in the CCA communities as
      compared to the control community.

PMID- 29634357
TI  - Global Survey of a Novel Smartphone Mobile Endoscopy System.
AB  - INTRODUCTION: The most commonly performed procedure among urologists is
      cystoscopy. However, urologists in developing countries have limited access and
      funds to purchase the equipment necessary to perform this procedure. The novel
      Endockscope (ES) mobile endoscopic system aids in reducing this gap in both cost
      and accessibility. MATERIALS AND METHODS: ES kits were distributed at the 2016
      World Congress of Endourology in Cape Town, South Africa. All participants were
      given instructions on how to use the device and each participant attended a live
      demonstration during the conference. Eight months later, all participants were
      contacted via email, regular mail, or phone to complete a questionnaire designed
      to assess the impact of the ES device. RESULTS: A total of 24 ES kits were
      distributed. After numerous emails, questionnaires sent by regular return mail,
      and phone calls, 12 (50%) participants completed the survey as instructed.
      Seventy percent of participants reported that they performed more endoscopic
      procedures due to the ES system. Overall, 90% of participants stated that they
      would purchase the ES system for personal use ($40.53). All participants reported
      that they would recommend the ES to others. CONCLUSION: The ES system provided an
      effective inexpensive system to enable urologists in resource-challenged
      countries to offer cystoscopy to more of their patients.

PMID- 29634358
TI  - The dynamics of the hand, foot and mouth disease epidemic from 2008 to 2016 in
      Zhenjiang city, China.
AB  - AIM: To investigate the hand, foot and mouth disease (HFMD) epidemic in
      Zhenjiang, China from 2008 to 2016. MATERIALS & METHODS: A total of 37,202 HFMD
      cases were investigated and 3707 nasopharyngeal swabs were detected for
      enterovirus RNA using RT-quantitative PCR. RESULTS: We first reported a mixed
      pattern of HFMD seasonal epidemic with a combination of single-peak and two-peak
      patterns in alternate years, and the occurrence of sporadic and epidemic
      outbreaks of HFMD in kindergartens in Zhenjiang. Children younger than 4 years of
      age were highly vulnerable to HFMD, and home children and boys had higher risk to
      develop severe HFMD than nursery children and girls, respectively. Among tested
      samples, 1709 (46.1%) were detected as enterovirus RNA positive. CONCLUSION: This
      study first presents the dynamic of the HFMD epidemic in Zhenjiang from 2008 to
      2016.

PMID- 29634359
TI  - The development of a vocabulary for PEEPS-SE-profiles of early expressive
      phonological skills for Swedish.
AB  - This paper describes the development of a vocabulary for Profiles of Early
      Expressive Phonological Skills for Swedish (PEEPS-SE), a tool for assessment of
      expressive phonology in Swedish-learning children in the age range of 18-36
      months. PEEPS-SE is the Swedish version of the original PEEPS, Profiles of Early
      Expressive Phonological Skills, which uses two age-adequate word lists-a basic
      word list (BWL) for the assessment of 18-24-month-old children, to which an
      expanded word list (EWL) is added for assessment of 24-36-month-old children, or
      children with more than 250 words in their expressive vocabulary. The selection
      of words in PEEPS-SE is based on two types of criteria: age of acquisition and
      phonological complexity. The words also need to be easy to elicit in a natural
      way in test situations. Vocabulary data previously collected with the Swedish
      Early Communicative Development Inventory are used for selection of age-adequate
      words, where the BWL contains words acquired earlier compared to the additional
      words in the EWL. The latter also contains words that are more phonologically
      complex compared to those in the BWL. Word complexity was determined by the
      Swedish version of word complexity measure. PEEPS-SE has made an attempt to match
      the original version of PEEPS in terms of both assessment method and word
      selection.

PMID- 29634361
TI  - Intracavitary therapies for upper tract urothelial carcinoma.
AB  - INTRODUCTION: While radical nephroureterectomy remains the gold-standard for
      upper tract urothelial carcinoma (UTUC), there is a growing push for organ
      sparing therapy in low-risk disease. Herein we review the use of intracavitary
      topical therapy for treatment of UTUC. Areas covered: A PubMed search was
      performed for studies pertaining to upper tract urothelial carcinoma, with 236
      articles reviewed, and distilled for content pertinent to intracavitary therapy
      for UTUC. Topics discussed include agents used for management of UTUC, most
      commonly BCG, as well as techniques for administration. Additionally, we review
      the evidence for curative treatment for Cis versus adjuvant therapy for Ta/T1
      disease. Finally, we discuss emerging technologies to improve agent delivery and
      efficacy in the upper tract. Expert commentary: No significant advances have
      occurred in topical management of UTUC in the past 2 decades. However, advances
      in diagnostic techniques such as modern ureteroscopes, and improved diagnostic
      imaging at the time of ureteroscopy may help improve our patient selection.
      Additional advances in topical therapy focused on increasing the duration of
      contact between agent delivered and the upper tract urothelium offer hope that a
      new leap forward in topical therapy is on the horizon.

PMID- 29634360
TI  - Sofosbuvir + velpatasvir + voxilaprevir for the treatment of hepatitis C
      infection.
AB  - INTRODUCTION: Hepatitis C is a disease with a significant global impact. Over the
      last several years, the treatment of the disease has been revolutionized. Therapy
      has transformed over the last several years with the approval of second
      generation direct acting antivirals, and currently utilized medications for the
      treatment of hepatitis C are significantly more efficacious with better safety
      profiles than previously approved treatments. Treatment for individuals who have
      failed therapy on direct acting antivirals has, until recently, been complex and
      difficult to treat, but the approval of sofosbuvir/velpatasvir/voxilaprevir
      represents a new therapeutic option for these individuals. Areas covered:
      Sofosbuvir/velpatasvir/voxilaprevir is a recently approved therapeutic
      combination for the treatment of hepatitis C. This article reviews the studies
      leading to the approval of the combination, and its efficacy and safety profile.
      Expert opinion: Sofosbuvir/velpatasvir/voxilaprevir fills one of the previously
      unfilled niches for the treatment of hepatitis C, that of the treatment of
      individuals who have failed therapy with resistant virus. With the filling of
      this niche, there appears to be a general slowing of the development of new
      therapeutics. Although understandable, in the long term, there are considerable
      risks associated with the decreased development of new drugs to treat hepatitis
      C.

PMID- 29634362
TI  - Transactional Sex and Preferences for Pre-Exposure Prophylaxis (PrEP)
      Administration Modalities Among Men Who Have Sex With Men (MSM).
AB  - Pre-exposure prophylaxis (PrEP) is an important biomedical human immunodeficiency
      virus (HIV) prevention tool gaining more popularity among Parisian men who have
      sex with men (MSM) who engage in transactional sex. This study examines the
      knowledge of, and willingness to use, different modalities of PrEP among this
      subgroup. Broadcast advertisements were placed on a geosocial-networking
      smartphone application with a link to a Web-based survey during three 24-hour
      periods in October 2016. Modified Poisson regression models were used to assess
      the association between engagement in transactional sex and preferences for each
      of these PrEP modalities. A total of 444 respondents were included. About 14%
      reported engagement in transactional sex. In all, 90% of MSM who engaged in
      transactional sex were knowledgeable of daily oral PrEP, while 13.3% were
      knowledgeable about long-acting injectable PrEP or penile or rectal microbicides.
      They were more likely to be aware of long-acting injectable PrEP (aRR = 2.52, 95%
      CI = 1.16 to 5.47) and willing to use daily oral PrEP (aRR = 1.48; 95% CI = 1.11
      to 1.98) or long-acting injectable PrEP (aRR = 1.40; 95% CI = 1.09 to 1.81) than
      MSM who had not engaged in transactional sex. Long-acting injectable PrEP may be
      an important HIV-prevention option for MSM who engage in transactional sex if
      this modality is proven effective.

PMID- 29634363
TI  - Reliability of Hypernasality Rating: Comparison of 3 Different Methods for
      Perceptual Assessment.
AB  - OBJECTIVE: To compare reliability in auditory-perceptual assessment of
      hypernasality for 3 different methods and to explore the influence of language
      background. DESIGN: Comparative methodological study. Participants and Materials:
      Audio recordings of 5-year-old Swedish-speaking children with repaired cleft lip
      and palate consisting of 73 stimuli of 9 nonnasal single-word strings in 3
      different randomized orders. Four experienced speech-language pathologists (2
      native speakers of Brazilian-Portuguese and 2 native speakers of Swedish)
      participated as listeners. After individual training, each listener performed the
      hypernasality rating task. Each order of stimuli was analyzed individually using
      the 2-step, VISOR and Borg centiMax scale methods. MAIN OUTCOME MEASURES:
      Comparison of intra- and inter-rater reliability, and consistency  for each
      method within language of the listener and between listener languages (Swedish
      and Brazilian-Portuguese). RESULTS: Good to excellent intra-rater reliability was
      found within each listener for all methods, 2-step: kappa = 0.59-0.93; VISOR:
      intraclass correlation coefficient (ICC) = 0.80-0.99; Borg centiMax (cM) scale:
      ICC = 0.80-1.00. The highest inter-rater reliability was demonstrated for VISOR
      (ICC = 0.60-0.90) and Borg cM-scale (ICC = 0.40-0.80). High consistency within
      each method was found with the highest for the Borg cM scale (ICC = 0.89-0.91).
      There was a significant difference in the ratings between the Swedish and the
      Brazilian listeners for all methods. CONCLUSIONS: The category-ratio scale Borg
      cM was considered most reliable in the assessment of hypernasality. Language
      background of Brazilian-Portuguese listeners influenced the perceptual ratings of
      hypernasality in Swedish speech samples, despite their experience in perceptual
      assessment of cleft palate speech disorders.

PMID- 29634364
TI  - Exploring the Medical and Psychosocial Concerns of Adolescents and Young Adults
      With Craniofacial Microsomia: A Qualitative Study.
AB  - OBJECTIVE: This study explores the experiences of adolescents and young adults
      with craniofacial microsomia, including the impact of growing up with this
      craniofacial condition on daily life and sense of self. The results may guide
      future research on optimally supporting individuals with craniofacial microsomia
      during this critical life phase. DESIGN AND SETTING: Participants were recruited
      through a craniofacial center, online patient support groups, and social media
      sites. Eleven individual semistructured interviews with participants between 12
      and 22 years old were conducted by a single interviewer, transcribed, iteratively
      coded, and thematically analyzed. RESULTS: Five themes were evident in the data:
      (1) impact on personal growth and character development, (2) negative
      psychosocial impact, (3) deciding to hide or reveal the condition, (4) desire to
      make personal surgical decisions, and (5) struggles with hearing loss.
      CONCLUSIONS: We identified both medical and psychosocial concerns prevalent among
      adolescents with craniofacial microsomia. Although adolescents with craniofacial
      microsomia exhibit considerable resilience, the challenges they face impact their
      sense of self and should be addressed through psychosocial support and
      counseling. Further research should investigate the potential benefit of the
      wider use of hearing aids, as well as the involvement of patients in decision
      making about reconstructive ear surgery.

PMID- 29634365
TI  - The consequences of 'Brexit' for drug discovery and development, and the
      regulatory implications.

PMID- 29634366
TI  - Feed the Alien! The Effects of a Nutrition Instruction Game on Children's
      Nutritional Knowledge and Food Intake.
AB  - OBJECTIVE: Serious games are a promising venue to increase children's nutritional
      knowledge in an entertaining format. The aim of this study was to test the short
      term effectiveness of the Alien Health Game, a videogame designed to teach
      elementary school children about nutrition and healthy food choices. MATERIALS
      AND METHODS: To examine the effects of the Alien Health Game, an experimental
      design with a single between-subjects factor (experimental condition vs. active
      control condition) was used. A total of 108 Dutch children (10-13 years; 58 boys)
      were randomly assigned to either play Alien Health using the Kinect sensor for
      two consecutive days, for 1 hour of gameplay (experimental condition; n = 50), or
      a web-based nutrition game for the same period (active control condition; n =
      58). Participants' nutritional knowledge was assessed at pretest, immediate, and
      at 2-week follow-up. Food intake was assessed at immediate and 2-week follow-up.
      RESULTS: Participants who played Alien Health had better knowledge of the five
      most important macronutrients of foods at immediate posttest, but not at follow
      up. Participants were better able to distinguish the healthier food item out of
      two options over time, but this effect did not differ for those in the
      experimental versus the active control condition. No differences in food intake,
      neither in the consumption of nutrient-dense or energy-dense foods, were found
      between children playing both games. CONCLUSION: A brief game-based intervention
      like the Alien Health Game has the potential to improve children's nutritional
      knowledge in the short term, but may not be strong enough to increase nutritional
      knowledge and actual eating behavior in the long term. Further investigation is
      warranted before this game is applied in future nutrition education programs.

PMID- 29634367
TI  - RNF4 regulates zebrafish granulopoiesis through the DNMT1-C/EBPalpha axis.
AB  - RING finger protein 4 (RNF4) is a multifunctional small ubiquitin-related
      modifier (SUMO)-targeted ubiquitin E3 ligase (STUbL) ubiquitously expressed in
      all tissues, and which mainly participates in DNA repair and in chromatin and
      transcriptional regulation. Although RNF4 has been implicated in hematopoietic
      disorders, its ontogenic role during hematopoietic development remains
      undiscovered. We generated a zebrafish rnf4 knockout line by using transcription
      activator-like effector nucleases technology to address the impact of rnf4 during
      hematopoiesis. Rnf4-deficient zebrafish embryos exhibited sharply decreased
      neutrophils numbers during both primitive and definitive hematopoiesis.
      Mechanistic studies revealed that repression of the key granulocytic activator,
      CCAAT/enhancer-binding protein alpha ( c/ebpalpha), via promoter hypermethylation
      by SUMOylated DNA methyltransferase 1 (DNMT1) was the main cause of impaired
      granulopoiesis in rnf4-deficient zebrafish. In addition, for the first time, we
      identified DNMT1 as a potential new STUbL substrate of RNF4, with knockdown of
      dnmt1 largely restoring primitive and definitive granulopoiesis in rnf4-deficient
      zebrafish. Collectively, RNF4 is indispensable for zebrafish granulopoiesis
      through regulation of the DNMT1-C/EBPalpha functional axis.-Wang, L., Liu, X.,
      Wang, H., Yuan, H., Chen, S., Chen, Z., de The, H., Zhou, J., Zhu, J. RNF4
      regulates zebrafish granulopoiesis through the DNMT1-C/EBPalpha axis.

PMID- 29634368
TI  - Cell adhesion protein fibulin-7 and its C-terminal fragment negatively regulate
      monocyte and macrophage migration and functions in vitro and in vivo.
AB  - Fibulin-7 (Fbln7) has been identified as the latest member of the fibulin family
      of secreted glycoproteins in developing teeth, functioning as a cell adhesion
      molecule and interacting with other matrix proteins, receptors, and growth
      factors. More recently, we have shown that the C-terminal Fbln7 fragment (Fbln7
      C) has antiangiogenic activity in vitro. Fbln7 is also expressed in immune
      privileged tissues, such as eye and placenta, but its functional significance is
      unknown. In the current study, we show that human monocytes adhere to both full
      length Fbln7 (Fbln7-FL) and Fbln7-C, in part, via integrins alpha5beta1 and
      alpha2beta1. Morphologic studies and surface expression analyses of CD14, mannose
      receptor (CD206), major histocompatibility complex II, and CD11b receptors
      revealed that both Fbln7-FL and Fbln7-C inhibit M-CSF-induced monocyte
      differentiation. Fbln7-C had significantly greater negative effects on cell
      spreading and stress fiber formation, including the production of IL-6 and
      metalloproteinase-1/-9 compared with Fbln7-FL. Furthermore, in an LPS-induced
      systemic inflammation model, Fbln7-C and Fbln7-FL reduced the infiltration of
      immune cells, such as neutrophils and macrophages, to the inflamed peritoneum.
      Thus, these results suggest that Fbln7 and Fbln7-C could modulate the activity of
      immune cells and have therapeutic potential for inflammatory diseases.-Sarangi,
      P. P., Chakraborty, P., Dash, S. P., Ikeuchi, T., de Vega, S., Ambatipudi, K.,
      Wahl, L., Yamada, Y. Cell adhesion protein fibulin-7 and its C-terminal fragment
      negatively regulate monocyte and macrophage migration and functions in vitro and
      in vivo.

PMID- 29634369
TI  - Predictors of Intrusive Sexual Behaviors in Preschool-Aged Children.
AB  - Intrusive sexual behaviors (ISBs) are a specific type of problematic sexual
      behavior characterized by the invasive nature of the acts (e.g., touching others'
      private parts, attempting intercourse; Friedrich, 1997). The limited amount of
      research on ISBs has focused on sexual abuse history as the primary predictor.
      However, Friedrich, Davies, Feher, and Wright (2003) found that ISBs in children
      up to age 12 were related to four broad conceptual factors: (a) exposure to
      sexual content, (b) exposure to violent behavior, (c) family adversity, and (d)
      child vulnerabilities. The current study sought to replicate Friedrich's study
      using a clinical sample of 217 preschool-aged children (ages two to six). Results
      supported variables from within the child vulnerabilities construct
      (externalizing behaviors, betaEXT = 0.032, p = 0.001), post-traumatic stress
      disorder (PTSD) criteria met (betaPTSD = 0.177, p = 0.02), and an inverse
      relationship with age (betaAGE = -0.206, p = 0.024). These results highlight the
      importance of considering childhood behavioral patterns and reactivity to
      traumatic events as correlates of ISBs in young children.

PMID- 29634371
TI  - Domestic Moods: Maternal Mental Health in Northern Vietnam.
AB  - In this article I propose the notion of domestic mood as an important concept for
      mental health research. Drawing on ethnographic fieldwork conducted among women
      living in Hanoi, Vietnam, I explore the maternal mental health problems that the
      women reported, focusing particularly on the household tensions and conflicts
      that made the entry into motherhood a distressful experience. To develop the
      concept of domestic mood, I draw on Martin Heidegger's work, particularly his
      claim that human being is always a being-with. Comprehending maternal mental
      health problems, I argue, requires that we pay attention not only to individual
      states of mind, but also to the ways that domestic environments shape people's
      moods. Taking this analytical approach, I show how the mental health states of
      pregnant women and new mothers in Vietnam were inseparable from their husbands'
      structural vulnerabilities within kin groups.

PMID- 29634372
TI  - Comparison of Central Corneal Thickness Measured by Standard Ultrasound
      Pachymetry, Corneal Topography, Tono-Pachymetry and Anterior Segment Optical
      Coherence Tomography.
AB  - PURPOSE: To compare central corneal thickness (CCT) measured by standard
      ultrasound pachymetry (USP), and three non-contact devices in healthy eyes.
      METHODS: A cross-sectional study of CCT measurement in 52 eyes of 52 healthy
      volunteers was done by a single examiner at Ocular Surface and Contact Lens
      Laboratory. Three consecutive measurements were done by standard USP, non-contact
      tono-pachymeter, Pentacam corneal topographer, and Anterior Segment Optical
      Coherence Tomography (AS-OCT). The mean values were used for assessment. The
      results were compared using multivariate ANOVA, linear regression, and Pearson
      correlation. Agreement among the devices was analyzed using mean differences and
      Bland-Altman analysis with 95% limits of agreement (LoA). Finally, reliability
      was analyzed using intraclass correlation coefficient (ICC). RESULTS: Mean CCT by
      ultrasound pachymeter, tono-pachymeter, corneal topographer and AS-OCT were 558.9
      +/- 31.2 um, 525.8 +/- 43.1 um, 550.4 +/- 30.5 um, and 545.9 +/- 30.5 um
      respectively. There was a significant positive correlation between AS-OCT and USP
      (Pearson correlation = 0.957, p < 0.001), corneal topography and USP (Pearson
      correlation = 0.965, p < 0.001), and corneal topography and AS-OCT (Pearson
      correlation = 0.965, p < 0.001). There was a lower correlation between CT-1P tono
      pachymeter and the other three modalities. Intraclass correlation coefficients
      show an excellent reliability between pairs except for CT-1P against the other
      three instruments that were found moderate. CONCLUSIONS: CT-1P tono-pachymeter
      underestimates CCT measurements compared to Scheimpflug system, AS-OCT device,
      and USP. Mean CCT among USP, Pentacam and AS-OCT were comparable and had
      significant linear correlations. In clinical practice, these three modalities
      could be interchangeable in healthy patients.

PMID- 29634370
TI  - Rod-Mediated Dark Adaptation and Macular Pigment Optical Density in Older Adults
      with Normal Maculas.
AB  - PURPOSE: To examine the association between macular pigment optical density
      (MPOD) and rod-mediated dark adaptation (RMDA) in persons >=60 years old with
      normal maculas as determined by an accepted color fundus photography grading
      system. METHODS: This cross-sectional analysis used baseline data from eyes in
      the Alabama Study on Early Age-Related Macular Degeneration. Eyes at step 1 in
      the AREDS 9-step grading system were considered normal. Eyes were additionally
      assessed by spectral domain optical coherence tomography (SD-OCT). Foveal MPOD
      was estimated via heterochromatic flicker photometry, and RMDA was assessed with
      a computerized dark adaptometer. The association between RMDA and MPOD was
      examined via Spearman correlation coefficients adjusted for age. RESULTS: In 306
      eyes from 306 persons (mean age 68.2 years) in normal macular health, MPOD was
      not associated with RMDA (age-adjusted rank correlation = 0.043, p = 0.45). After
      81 eyes with incidental macular findings by SD-OCT evaluation were excluded, the
      association between MPOD and RMDA remained null (N = 225, age-adjusted r = 0.015,
      p = 0.82). CONCLUSION: In a large sample of normal aged eyes, RMDA, a visual
      function that is rate limited by retinoid availability to photoreceptors across
      the complex of retinal pigment epithelium, Bruch's membrane, and
      choriocapillaris, is not related to MPOD in the neurosensory retina.

PMID- 29634373
TI  - Potential Alternative Treatment of Ocular Bacterial Infections by Oil Derived
      from Syzygium aromaticum Flower (Clove).
AB  - : Purpose/Aim: This study aims to evaluate the predisposing risk factors and
      antibiotic resistance of bacterial corneal ulcer to commonly used antibiotics. In
      addition, assess the in vitro efficacy of plant-derived essential oils (EOs) as
      safe and effective antimicrobial agents. METHODS: Demographic features and
      predisposing risk factors of corneal ulcer patients were recorded. Isolation and
      identification of bacteria was performed using conventional microbiological
      methods. Antibacterial activity was determined by disk diffusion and the micro
      dilution broth methods. EOs were extracted by steam distillation and were
      analyzed by gas chromatography mass spectrometry technique. RESULTS: Out of the
      200 patients with corneal ulcer evaluated in this study, the main predisposing
      factor of bacterial corneal ulcer was trauma (26.5%) and 96.7% isolates were
      multidrug resistant. Staphylococcus aureus was the predominant isolate 33 cases.
      Antibiotic susceptibility of bacterial isolates showed that the fourth-generation
      fluoroquinolones, gatifloxacin was the most effective antibiotic with sensitivity
      rate 81.3%. Seven selected EOs showed significant activity against most of the
      tested bacteria. Syzygium aromaticum oil showed high activity against all tested
      bacterial species with highest sensitivity rate (97.5%) and low minimal
      inhibitory concentration values against S. aureus (0.10 ul/ml). The chemical
      composition of the EOs showed that the monoterpenes were predominant. The main
      constituent of S. aromaticum oil was eugenol (76%). CONCLUSIONS: The current
      study showed that S. aromaticum oil had high antibacterial activity that could be
      helpful in the treatment of ocular bacterial infections to minimizing the
      possible side effects of commonly used antibiotic.

PMID- 29634374
TI  - Extending the Theory of Normative Social Behavior to Predict Hand-Washing among
      Koreans.
AB  - The current study tests the predictions of the theory of normative social
      behavior (TNSB) in a hand-washing context in a Korean sample and extends the
      theory to examine the role of perceived publicness, a variable believed to
      activate face concerns, as a moderator of the norm-behavior relationship. The
      findings show substantial main effects for all of the study variables on
      behavior. In addition, the descriptive norm-behavior relationship is moderated by
      perceived publicness and outcome expectations, but the nature of the interactions
      is not consistent with that evidenced in previous literature on US samples.
      Implications for normative theory and communication campaigns are discussed.

PMID- 29634375
TI  - Analgesic Effect of Topical Nepafenac 0.1% on Pain Related to Intravitreal
      Injections: A Randomized Crossover Study.
AB  - PURPOSE: To evaluate the analgesic effect of nepafenac 0.1%, a topical non
      steroidal anti-inflammatory agent, in patients undergoing treatment with
      intravitreal injections (IVIs). MATERIAL AND METHODS: It is a single center,
      prospective, randomized, double-blinded, placebo-controlled, crossover
      interventional study. Fifty-two patients scheduled to undergo IVI of anti
      vascular endothelial growth factors were included in the study. Patients were
      randomized in a 1:1 ratio to receive topical nepafenac 0.1% or placebo 1 h before
      subsequent IVIs. Using the short form of the McGill Pain Questionnaire (SF-MPQ),
      pain intensity was assessed with the Visual Analogue Scale (VAS), the Main
      Component of the SF-MPQ (MC-SF-MPQ), and the Present Pain Intensity (PPI) scores
      immediately and 6-h post-injection. RESULTS: The VAS pain score was statistically
      significant lower immediately and 6-h post-IVI in patients treated with nepafenac
      (p = 0.001 and < 0.001, respectively). The MC-SF-MPQ scores were also
      statistically significant lower after nepafenac administration at both time
      points (p < 0.001). Finally, the PPI score was statistically significant lower
      when nepafenac was instilled before IVI (p = 0.015 immediately and p < 0.001 at 6
      h post-injection). CONCLUSIONS: A single drop of nepafenac 0.1% before IVI could
      effectively alleviate the IVI-related pain immediately and up to 6 h after the
      injection.

PMID- 29634376
TI  - Outpatient Percutaneous Nephrolithotomy: The UC San Diego Health Experience.
AB  - INTRODUCTION: Outpatient percutaneous nephrolithotomy (PCNL) has been described
      for highly selected patients. We sought to assess the safety and feasibility of
      outpatient PCNL in a tertiary referral stone center without strict patient
      selection criteria. MATERIALS AND METHODS: We reviewed all PCNLs performed at our
      institution from September 2015 to October 2016. Of the 97 eligible cases, 60
      patients underwent planned outpatient PCNL. Primary outcome was complication
      rate, and secondary outcome determined predictor variables of inpatient
      admission. RESULTS: Thirty-seven inpatient and 60 planned outpatient (one
      bilateral) PCNLs were performed with 65% and 44% American Society of
      Anesthesiologists (ASA) score >=3, respectively. The 30-day overall complication
      rate for the inpatient and planned outpatient groups was 27% and 20%,
      respectively (p = 0.43) [70% and 92% Clavien grades I-II]. Emergency department
      presentation within 30 days was 19% and 18% (p = 0.94), and unplanned hospital
      readmission rate was 3% and 10% (p = 0.05). The 37 inpatient PCNL patients had
      larger total stone burden than outpatient cases (40.7 vs 25.8 mm, p = 0.0014);
      more often required two or more punctures into the kidney during the procedure
      (73% vs 45%, p = 0.025); and more often had supracostal access (20% vs 7%, p =
      0.05). For the outpatient PCNL cohort, 72% patients were discharged same day, 28%
      were observed overnight for refractory symptoms or social reasons. Outpatient
      cohort radiographic stone-free rate by CT (no stones) was 67%. CONCLUSION:
      Outpatient PCNL has been safely and effectively performed within our institution
      in moderate-sized stones almost regardless of comorbidity status. We suggest that
      this approach is a potential algorithmic change in centers with sufficient case
      volume.

PMID- 29634377
TI  - The Role of Self-Conscious Emotions in the Sexual Health of Gay and Bisexual Men:
      Psychometric Properties and Theoretical Validation of the Sexual Shame and Pride
      Scale.
AB  - Researchers have theorized about the role of sexual shame as a mechanism through
      which sexual minority stress manifests into mental health difficulties, such as
      sexual compulsivity for gay and bisexual men (GBM), and about the resilience
      promoting effects of sexual pride. However, no validated measures to date have
      directly tapped into these constructs rather than using proxies for them, such as
      internalized homonegativity. We developed the Sexual Shame and Pride Scale (SSPS)
      and conducted a psychometric evaluation of it using a sample of 260 highly
      sexually active GBM. The scale had the expected structure in factor analysis and
      showed evidence of internal consistency and test-retest reliability.
      Correlational analyses demonstrated the convergent validity of sexual shame and
      sexual pride with relevant constructs. Regression analyses demonstrated the
      predictive validity of sexual shame in relation to sexual compulsivity,
      accounting for unique variability even after adjusting for previously
      demonstrated etiological factors, and the predictive validity of both shame and
      pride, which interacted to consistently predict four sexual behavior outcomes.
      Findings suggest the SSPS is a psychometrically valid and reliable measure that
      may be useful in future empirical work and highlight preliminary evidence for the
      role of these constructs in the sexual health of GBM.

PMID- 29634378
TI  - Effect of intensive versus standard blood pressure control on major adverse
      cardiac events and serious adverse events: A bivariate analysis of randomized
      controlled trials.
AB  - BACKGROUND: Intensive blood pressure (BP) lowering may offer protective effects
      against major adverse cardiac event (MACE) but is also associated with a greater
      risk of a serious adverse event (SAE). The risk-benefit profile of intensive
      versus standard BP control has not been comprehensively assessed. METHODS: Four
      studies were identified from a systematic literature search for randomized
      controlled trials comparing intensive versus standard BP lowering that reported
      both MACE and SAE endpoints. A previously described statistical approach was
      applied to characterize the efficacy-safety tradeoff of BP control. The bivariate
      outcome was computed to quantitatively assess the net clinical benefit (NCB) of
      intensive BP lowering as compared to standard treatment, with positive values
      indicating increased risks and negative values indicating decreased risks.
      RESULTS: Data from the SPRINT trial demonstrated that intensive strategy was
      superior in MACE but inferior in SAE, thereby eroding the NCB (bivariate outcome:
      0.33% [-0.50% to 1.21%]). Intensive strategy from the SPS3 trial fulfilled non
      inferiority in both MACE and SAE but did not reach a favorable NCB (-1.31% [
      2.25% to 0.01%]). The ACCORD trial suggested that intensive strategy was non
      inferior in MACE but inferior in SAE (-0.19% [-0.79% to 1.37%]). Results from the
      VALISH trial were inconclusive for SAE but suggested non-inferiority in MACE (
      1.19% [-3.24% to 0.68%]). CONCLUSIONS: Compared to the standard blood pressure
      target, pooled data from randomized controlled trials suggest that intensive
      strategy did not achieve a net clinical benefit when weighing the benefit of MACE
      reduction against the risk of SAE under the bivariate framework. ABBREVIATIONS:
      Blood pressure (BP), diastolic blood pressure (DBP), major adverse cardiac event
      (MACE), net clinical benefit (NCB), serious adverse event (SAE), systolic blood
      pressure (SBP).

PMID- 29634379
TI  - Visual Pathway Measures are Associated with Neuropsychological Function in
      Multiple Sclerosis.
AB  - PURPOSE: To determine the relationships between visual function and ganglion cell
      and inner plexiform layer thickness and neuropsychological measures in multiple
      sclerosis (MS). METHODS: Ninety-five relapsing-remitting MS (RRMS) and 36
      progressive MS patients underwent 100%-contrast visual acuity (VA), 2.5%- and
      1.25%-contrast letter acuity (LA) testing, Cirrus-HD-optical coherence
      tomography, and neuropsychological assessments. Mixed-effects regression models
      were used to assess relationships. RESULTS: Across the cohort, 1.25%-contrast LA
      was associated with Symbol Digit Modalities Test (SDMT; beta = 2.17, p = 0.005)
      and Brief Visuospatial Memory Test-Revised (BVMT-R) total recall (TR) and delayed
      recall (DR) scores (beta = 0.31, p < 0.001; beta = 0.15, p = 0.039,
      respectively). 2.5%-contrast LA was associated with BVMT-R TR scores (beta =
      0.27, p = 0.006). In the RRMS cohort, 1.25%-contrast LA was generally more
      significantly associated with cognitive measures: SDMT (beta = 2.97, p = 0.001)
      and BVMT-R TR (beta = 0.32, p < 0.001) and DR (beta = 0.22, p = 0.012).
      CONCLUSION: This study suggests that visual pathway measures, particularly visual
      function measures, reflect aspects of cognitive function in MS, further
      supporting their roles as complementary outcomes in MS neuroprotection trials.

PMID- 29634380
TI  - Future Directions for Examination of Brain Networks in Neurodevelopmental
      Disorders.
AB  - Neurodevelopmental disorders are associated with atypical development and
      maturation of brain networks. A recent focus on human connectomics research and
      the growing popularity of open science initiatives has created the ideal climate
      in which to make real progress toward understanding the neurobiology of disorders
      affecting youth. Here we outline future directions for neuroscience researchers
      examining brain networks in neurodevelopmental disorders, highlighting gaps in
      the current literature. We emphasize the importance of leveraging large
      neuroimaging and phenotypic data sets recently made available to the research
      community, and we suggest specific novel methodological approaches, including
      analysis of brain dynamics and structural connectivity, that have the potential
      to produce the greatest clinical insight. Transdiagnostic approaches will also
      become increasingly necessary as the Research Domain Criteria framework put forth
      by the National Institute of Mental Health permeates scientific discourse. During
      this exciting era of big data and increased computational sophistication of
      analytic tools, the possibilities for significant advancement in understanding
      neurodevelopmental disorders are limitless.

PMID- 29634381
TI  - Efficacy of HL036 versus Cyclosporine A in the Treatment of Naturally Occurring
      Canine Keratoconjunctivitis Sicca.
AB  - PURPOSES: To (i) evaluate the efficacy and safety of HL036, a tumor-necrosis
      factor (TNF)-alpha-blocking protein, in the treatment of naturally occurring
      canine keratoconjunctivitis sicca (KCS) and (ii) compare these features with
      those of 1% cyclosporine A (CsA). MATERIALS AND METHODS: Dogs (n = 29) diagnosed
      with KCS were randomly assigned to receive one drop topical aqueous HL036 (0.2,
      1, or 5 mg/mL) or 1% CsA in the affected eye(s) at 12-h intervals for 42 days.
      Schirmer's tear test (STT), fluorescein corneal staining (FCS), and clinical-sign
      scores were evaluated prior to application (day-0) and on days 14, 28, and 42
      post-treatment. Of the 29 dogs enrolled, 19 (65.5%) received HL036 (HL036 group)
      and 10 (34.5%) received 1% CsA (CsA group). A linear mixed-effects model analysis
      was performed to determine score differences between groups and over time.
      RESULTS: After treatment, clinical-sign scores and STT values had significantly
      improved compared with baseline levels in dogs of both treatment groups.
      Decreases in total clinical-sign scores for the HL036-group were greater than
      those of 1% CsA group. No severe adverse reactions were noted in either group.
      CONCLUSIONS: Our findings suggest that topical aqueous HL036 is well-tolerated
      and more effective than 1% CsA for treating naturally occurring canine KCS.

PMID- 29634382
TI  - Early photoreceptor outer segment loss and retinoschisis in Cohen syndrome.
AB  - PURPOSE: To describe early structural and functional retinal changes in a patient
      with Cohen syndrome. METHODS: A 13-month-old Caucasian girl of Irish and Spanish
      ancestry was noted to have micrognathia and laryngomalacia at birth, which
      prompted a genetic evaluation that revealed biallelic deletions in COH1 (VPS13B)
      (a maternally inherited 60-kb deletion involving exons 26-32 and a paternally
      inherited 3.5-kb deletion within exon 17) consistent with Cohen syndrome. She
      underwent a complete ophthalmic examination, full-field flash electroretinography
      and retinal imaging with spectral domain optical coherence tomography. RESULTS:
      Central vision was central, steady, and maintained. There was bilateral myopic
      astigmatic refractive error. Fundus exam was notable for dark foveolar
      pigmentation, but no obvious abnormalities of either eye. Spectral domain optical
      coherence tomography cross sections through the fovea revealed a normal appearing
      photoreceptor outer nuclear layer but loss of the interdigitation signal between
      the photoreceptor outer segments and the apical retinal pigment epithelium.
      Retinoschisis involving the inner nuclear layer of both eyes and possible
      ganglion cell layer thinning were also noted. There was a detectable
      electroretinogram with similarly reduced amplitudes of rod- (white, 0.01 cd.s.m
      2) and cone-mediated (3 cd.s.m-2, 30 Hz) responses. CONCLUSION: Photoreceptor
      outer segment abnormalities and retinoschisis may represent the earliest
      structural retinal change detected by spectral domain optical coherence
      tomography in patients with Cohen syndrome, suggesting a complex pathophysiology
      with primary involvement of the photoreceptor cilium and disorganization of the
      structural integrity of the inner retina.

PMID- 29634383
TI  - Clinical pharmacogenomics testing in the era of next generation sequencing:
      challenges and opportunities for precision medicine.
AB  - INTRODUCTION: The rapid development and dramatic decrease in cost of sequencing
      techniques have ushered the implementation of genomic testing in patient care.
      Next generation DNA sequencing (NGS) techniques have been used increasingly in
      clinical laboratories to scan the whole or part of the human genome in order to
      facilitate diagnosis and/or prognostics of genetic disease. Despite many hurdles
      and debates, pharmacogenomics (PGx) is believed to be an area of genomic medicine
      where precision medicine could have immediate impact in the near future. Areas
      covered: This review focuses on lessons learned through early attempts of
      clinically implementing PGx testing; the challenges and opportunities that PGx
      testing brings to precision medicine in the era of NGS. Expert commentary:
      Replacing targeted analysis approach with NGS for PGx testing is neither
      technically feasible nor necessary currently due to several technical limitations
      and uncertainty involved in interpreting variants of uncertain significance for
      PGx variants. However, reporting PGx variants out of clinical whole exome or
      whole genome sequencing (WES/WGS) might represent additional benefits for
      patients who are tested by WES/WGS.

PMID- 29634384
TI  - Inhibition of breast cancer cell growth by the combination of clofarabine and
      sulforaphane involves epigenetically mediated CDKN2A upregulation.
AB  - Many antineoplastic nucleoside analogue-based combinatorial strategies focused on
      remodelling aberrant DNA methylation patterns have been developed. The number of
      studies demonstrate high efficacy of bioactive phytochemicals in support of
      conventional chemotherapy. Our recent discoveries of the epigenetic effects of
      clofarabine (2'-deoxyadenosine analogue, antileukaemic drug) and clofarabine
      based combinations with dietary bioactive compounds in breast cancer cells led us
      to look for more DNA methylation targets of these cancer-preventive agents. In
      the present study, using methylation-sensitive restriction analysis (MSRA) and
      qPCR, we showed that clofarabine in combination with sulforaphane, a
      phytochemical from cruciferous vegetables, significantly reactivates DNA
      methylation-silenced CDKN2A tumour suppressor and inhibits cancer cell growth at
      a non-invasive breast cancer stage.

PMID- 29634385
TI  - Anterior cruciate ligament reconstruction complicated by Propionibacterium acnes
      infection: case series.
AB  - Anterior cruciate ligament (ACL) reconstruction is one of the most commonly
      performed orthopaedic procedures. While generally successful, failure resulting
      in revision surgery is reported to be between 1.9 - 4.9%. However, when not
      related to traumatic re-injury, failure mechanism is poorly understood. One
      potential but understudied mechanism of ACL reconstruction failure is infection.
      We describe three patients with previous ACL reconstructions who later developed
      infection with Propionibacterium acnes. Two cases presented with knee pain and
      swelling, and one presented with instability. While only two of the three cases
      received antibiotic treatment, all three cases were free of knee and infectious
      symptomatology at most recent follow-up. P. acnes infection may represent one
      potential mechanism for biologic failure of ACL reconstruction and anaerobic
      operative cultures may be used to identify its presence.

PMID- 29634386
TI  - Physiological self-regulation and mindfulness in children with a diagnosis of
      fetal alcohol spectrum disorder.
AB  - OBJECTIVE: To explore the differences in baseline respiratory sinus arrhythmia
      (RSA) between children with fetal alcohol spectrum disorder (FASD) and typically
      developing children (TDC) and to investigate whether children with FASD have the
      capacity to engage in a brief mindfulness exercise. METHODS: Participants were 14
      children with FASD and 20 TDC. RSA was measured at baseline, during, and
      following a mindfulness exercise. A mindfulness compliance checklist was
      completed to ascertain if children could follow the task instructions. RESULTS:
      Both groups obtained high scores on the mindfulness compliance checklist. There
      was a trend for children with FASD to have lower baseline RSA compared to TDC.
      Children in both groups demonstrated an increase in RSA during the mindfulness
      task. CONCLUSIONS: Children with FASD could engage in a mindfulness task, and
      both groups showed an increase in RSA. Further research is needed to establish
      whether prolonged mindfulness practice could be beneficial.

PMID- 29634387
TI  - "Examining RAS pathway rewiring with a chemically inducible activator of RAS".
AB  - RAS signaling pathways govern diverse cellular processes, are dynamic, and
      exhibit marked plasticity. Yet, these features also present a considerable
      obstacle to their study. Here, we report the use of a recently described RAS
      rheostat, Chemically Inducible Activator of RAS (CIAR), to study two poorly
      understood phenomena in RAS biology. First, we show that short-term activation of
      wild type endogenous RAS can desensitize cells to EGF stimulation. Second, we
      examine the phenomena of paradoxical activation of RAS/ERK signaling by RAF
      inhibitors. Specifically, we characterize the effects on RAS/ERK signaling
      kinetics of four RAF inhibitors, which stabilize distinct ATP-binding site
      conformations. These results demonstrate the utility of CIAR in conducting
      quantitative studies of complex features of RAS biology.

PMID- 29634388
TI  - Abstracts from Women's Health 2018: Translating Research into Clinical Practice
      May 4-6, 2018 Washington, DC.

PMID- 29634391
TI  - Collaborating with Adolescents and Young Adults with Cancer as Advisors.
AB  - There is a growing interest by both pediatric and medical oncologists to develop
      adolescent and young adult (AYA)-specific cancer programs. Input from AYA
      patients is critical to the successful design of these programs and to ensuring
      that patient needs are met. As traditional in-person advisory groups may not be
      the most appropriate means for engaging AYAs, this article describes the creation
      and implementation of a novel, developmentally appropriate, and efficient Young
      Adult Advisory Program. Reach, uptake, and participant demographic and clinical
      characteristics are presented alongside lessons learned. The findings are offered
      to assist others seeking to engage AYAs in program development and quality
      improvement efforts.

PMID- 29634390
TI  - Crosstalk between lysine methylation and phosphorylation of ATG16L1 dictates the
      apoptosis of hypoxia/reoxygenation-induced cardiomyocytes.
AB  - Post-translational modifications of autophagy-related (ATG) genes are necessary
      to modulate their functions. However, ATG protein methylation and its
      physiological role have not yet been elucidated. The methylation of non-histone
      proteins by SETD7, a SET domain-containing lysine methyltransferase, is a novel
      regulatory mechanism to control cell protein function in response to various
      cellular stresses. Here we present evidence that the precise activity of ATG16L1
      protein in hypoxia/reoxygenation (H/R)-treated cardiomyocytes is regulated by a
      balanced methylation and phosphorylation switch. We first show that H/R promotes
      autophagy and decreases SETD7 expression, whereas autophagy inhibition by 3-MA
      increases SETD7 level in cardiomyocytes, implying a tight correlation between
      autophagy and SETD7. Then we demonstrate that SETD7 methylates ATG16L1 at lysine
      151 while KDM1A/LSD1 (lysine demethylase 1A) removes this methyl mark.
      Furthermore, we validate that this methylation at lysine 151 impairs the binding
      of ATG16L1 to the ATG12-ATG5 conjugate, leading to inhibition of autophagy and
      increased apoptosis in H/R-treated cardiomyocytes. However, the cardiomyocytes
      with shRNA-knocked down SETD7 or inhibition of SETD7 activity by a small molecule
      chemical, display increased autophagy and decreased apoptosis following H/R
      treatment. Additionally, methylation at lysine 151 inhibits phosphorylation of
      ATG16L1 at S139 by CSNK2 which was previously shown to be critical for autophagy
      maintenance, and vice versa. Together, our findings define a novel modification
      of ATG16L1 and highlight the importance of an ATG16L1 phosphorylation-methylation
      switch in determining the fate of H/R-treated cardiomyocytes.

PMID- 29634392
TI  - Ragweed sublingual tablet immunotherapy: part I - evidence-based clinical
      efficacy and safety.
AB  - Sublingual tablet immunotherapy provides an attractive alternative approach to
      allergen immunotherapy, as the allergen is administered as a rapidly dissolving
      sublingual tablet. Part I of this two-part series on the ragweed sublingual
      tablet describes the dose-ranging clinical work, the safety studies and the
      clinical outcomes from the pivotal trials which provide clear evidence for
      statistically significant and clinically meaningful benefit in the treatment of
      patients suffering from ragweed-induced seasonal allergic rhinitis-conjunctivitis
      with or without milder asthma. The robust results observed in the clinical trials
      performed with the ragweed sublingual tablet are defined by the quality of their
      study design, their use of a standardized allergen extract, their consistent
      reproducibility in demonstrating therapeutic efficacy and their properly
      quantified and graded safety data.

PMID- 29634393
TI  - High-Throughput Flow Cytometric Method for the Simultaneous Measurement of CAR-T
      Cell Characterization and Cytotoxicity against Solid Tumor Cell Lines.
AB  - High-throughput flow cytometry is an attractive platform for the analysis of
      adoptive cellular therapies such as chimeric antigen receptor T cell therapy (CAR
      T) because it allows for the concurrent measurement of T cell-dependent cellular
      cytotoxicity (TDCC) and the functional characterization of engineered T cells
      with respect to percentage of CAR transduction, T cell phenotype, and measurement
      of T cell function such as activation in a single assay. The use of adherent
      tumor cell lines can be challenging in these flow-based assays. Here, we present
      the development of a high-throughput flow-based assay to measure TDCC for a CAR-T
      construct co-cultured with multiple adherent tumor cell lines. We describe
      optimal assay conditions (such as adherent cell dissociation techniques to
      minimize impact on cell viability) that result in robust cytotoxicity assays. In
      addition, we report on the concurrent use of T cell transduction and activation
      antibody panels (CD25) that provide further dissection of engineered T cell
      function. In conclusion, we present the development of a high-throughput flow
      cytometry method allowing for in vitro interrogation of solid tumor, targeting
      CAR-T cell-mediated cytotoxicity, CAR transduction, and engineered T cell
      characterization in a single assay.

PMID- 29634394
TI  - Invasive Dental Treatment and Risk for a First Myocardial Infarction.
AB  - Invasive dental treatment is suggested to be associated with an increased risk
      for the development of cardiovascular events. We tested the hypothesis that the
      incidence of a first myocardial infarction (MI) within 4 wk after invasive dental
      treatments is increased. A registry-based case-control study within nationwide
      health care and population registries in Sweden was performed. The case patients
      included 51,880 individuals with a first fatal or nonfatal MI between January
      2011 and December 2013. For each case, 5 control subjects, free from prior MI and
      matched for age, sex, and geographic area of residence, were randomly selected
      from the national population registry through risk set sampling with replacement,
      resulting in 246,978 control subjects. Information on dental treatments was
      obtained from the Dental Health Register, and the procedures were categorized
      into invasive dental treatments or other dental treatments. Conditional logistic
      regression was used to estimate odds ratios (ORs) for MI with corresponding 95%
      confidence intervals (CIs). In addition to the matching variables, adjustments
      were made for the following confounders: diabetes, previous cardiovascular
      disease (CVD), CVD drug treatment, education, and income. The mean age for case
      patients and controls subjects was 72.6 +/- 13.0 y and 72.3 +/- 13.0 y,
      respectively. Case patients more often had previous CVD (49% vs. 23%; P < 0.001)
      and diabetes (19% vs. 11%; P < 0.001) and received more treatment with CVD drugs
      (68% vs. 56%; P < 0.001) than control subjects. There was no association between
      invasive dental treatments during the 4 wk preceding the MI index date (crude OR
      = 0.99; 95% CI, 0.92 to 1.06; adjusted for confounders OR = 0.98; 95% CI, 0.91 to
      1.06). This study did not support the hypothesis of an increased incidence of MI
      after recent invasive dental treatment.

PMID- 29634395
TI  - Quantification of Histidine-Rich Protein 3 of Plasmodium falciparum.
AB  - Malaria is a life-threatening infectious disease and continues to be a major
      public health crisis in many parts of the tropical world. Plasmodium falciparum
      is responsible for the majority of mortality and morbidity associated with
      malaria. During the intraerythrocytic cycle, P. falciparum releases three
      proteins with high histidine content as follows: histidine-rich protein 1 (HRP1),
      histidine-rich protein 2 (HRP2), and histidine-rich protein 3 (HRP3). Currently,
      most of the diagnostic tests of P. falciparum infection target HRP2, and a number
      of monoclonal antibodies (mAbs) against HRP2 have been developed for use in HRP2
      detection and quantification. When parasites have HRP2 deletions, the detection
      of HRP3 could augment the sensitivity of the detection system. The combination of
      both HRP2 and HRP3 mAbs in the detection system will enhance the test
      sensitivity. In the HRP quantitative enzyme-linked immunosorbent assay (ELISA),
      both HRP2 and HRP3 contribute to the result, but the relative contribution of
      HRP2 and HRP3 was unable to investigate, because of the nonavailability of HRP3
      specific antibody ELISA. Hence an ELISA test system based on HRP3 is also
      essential for detection and quantification. There is not much documented in the
      literature on HRP3 antigen and HRP3 specific mAbs and polyclonal antibodies
      (pAbs). In the present study, recombinant HRP3 was expressed in Escherichia coli
      and purified with Ni-NTA agarose column. The purified rHRP3 was used for the
      generation and characterization of monoclonal and pAbs. The purification of
      monoclonal and pAbs was done using a mixed-mode chromatography sorbent,
      phenylpropylamine HyperCelTM. With the purified antibodies, a sandwich ELISA was
      developed. The sandwich ELISA method was explored to detect and quantify HRP3 of
      P. falciparum in the spent medium. The generated mAbs could be potentially used
      for the detection and quantification of P. falciparum HRP3.

PMID- 29634397
TI  - Aicar effect in early neuronal development.
AB  - : The neurological manifestations of Lesch-Nyhan disease (LND) have been
      attributed to the effect of hypoxanthine-guanine phosphoribosyltransferase (HPRT)
      deficiency on nervous system development. An increase has been reported in the
      levels of 5-aminoimidazole-4-carboxamide-1-beta-D-ribotide (AICAR) and its
      triphosphate form ZTP in the red blood cells of patients with LND. AICAR
      accumulation in the brain has been hypothesized as the cause of some of the
      neurological symptoms of patients with LND. In this study, we examined the effect
      of AICAR on the differentiation of neurons in the well-established human NTERA-2
      cl.D1 (NT2/D1) embryonic carcinoma neurogenesis model. NT2/D1 cells were
      differentiated along neuroectodermal lineages after exposure to 10-uM retinoic
      acid (RA), with or without the addition of 25-uM AICAR to the culture medium. The
      effect of AICAR on RA differentiation were examined through changes in the
      expression of genes essential to neuronal differentiation, as well as genes from
      the Wnt/beta-catenin, transforming growth factor beta (TGFbeta) and sonic
      hedgehog (SHH) pathways. RESULTS: RA-induced differentiation in the NT2/D1 cells
      significantly increased the expression of MAP2, NRG1, NRP1, NRP2, NEUROG1 and EN1
      genes (genes linked to neural differentiation) compared with undifferentiated
      NT2/D1 cells. We found that AICAR increased the expression of the SHH gene and
      the WNT2 and WNT7B genes but did not influence the expression of genes whose
      overexpression characterize early neurodevelopmental processes. CONCLUSION: The
      relevance of the AICAR related changes in the SHH and Wnt/beta-catenin pathway
      genes expression in the physiopathology of LND warrants further exploration.

PMID- 29634398
TI  - Dietary Changes and Gut Dysbiosis in Children With Type 1 Diabetes.
AB  - OBJECTIVE: Gut dysbiosis in type 1 diabetes (T1D), characterized by high
      Bacteroides proportion, tends to reverse as T1D progresses, without reaching full
      recovery. Since diet influences microbiota structure, the aim was to evaluate the
      impact of dietary changes on Bacteroides proportion the first year of T1D
      evolution. METHODS: Dietary intake was assessed by 24-hour recalls and
      Bacteroides proportion by quantitative polymerase chain reaction, in 10 Mexican
      children (11.6 +/- 1.92 years) with T1D at baseline and 3, 6 and 9 months' follow
      up. Repeated measures analysis of variance and multiple linear regression were
      performed to compare ingested nutrients in relation with Bacteroides proportion.
      Effects over time were evaluated by mixed regression models. RESULTS: Patients
      with T1D decreased their energy (2621.89 to 1867.85 kcal, p = 0.028), protein
      (83.06 to 75.17 g, p = 0.012), and saturated fat consumption (40.83 to 25.23 g, p
      = 0.031) from baseline to 3 months, without posterior changes. Bacteroides
      proportion increased in the first months and tended to decrease at around 9
      months (p > 0.05) and was positively correlated with saturated fat (beta = 3.70,
      p = 0.009) and total carbohydrates (beta = 0.73, p = 0.005) at 3 months.
      Carbohydrate consumption was related to decreased Bacteroides abundance over time
      (beta = -14.9, p = 0.004), after adjusting for glycosylated hemoglobin.
      CONCLUSIONS: Besides autoimmunity, diet appears to have a central role
      determining the T1D-associated dysbiosis evolution.

PMID- 29634396
TI  - Localized Delivery of Amifostine Enhances Salivary Gland Radioprotection.
AB  - Radiotherapy for head and neck cancers commonly causes damage to salivary gland
      tissue, resulting in xerostomia (dry mouth) and numerous adverse medical and
      quality-of-life issues. Amifostine is the only Food and Drug Administration
      approved radioprotective drug used clinically to prevent xerostomia. However,
      systemic administration of amifostine is limited by severe side effects,
      including rapid decrease in blood pressure (hypotension), nausea, and a narrow
      therapeutic window. In this study, we demonstrate that retroductal delivery of
      amifostine and its active metabolite, WR-1065, to murine submandibular glands
      prior to a single radiation dose of 15 Gy maintained gland function and
      significantly increased acinar cell survival. Furthermore, in vivo stimulated
      saliva secretion was maintained in retrograde-treated groups at levels
      significantly higher than irradiated-only and systemically treated groups. In
      contrast to intravenous injections, retroductal delivery of WR-1065 or amifostine
      significantly attenuated hypotension. We conclude that localized delivery to
      salivary glands markedly improves radioprotection at the cellular level, as well
      as mitigates the adverse side effects associated with systemic administration.
      These results support the further development of a localized delivery system that
      would be compatible with the fractionated dose regimen used clinically.

PMID- 29634399
TI  - Down-Regulated miR-125a-5p Promotes the Reprogramming of Glucose Metabolism and
      Cell Malignancy by Increasing Levels of CD147 in Thyroid Cancer.
AB  - BACKGROUND: CD147 contributes to increased aerobic glycolysis through which it
      promotes tumor growth. Accumulating evidence suggests that CD147 exerts a variety
      of functions in thyroid cancer (TC) progression but the molecular mechanisms and
      therapeutic value of CD147 remain unclear. METHODS: CD147 levels in TC tissues
      were analyzed to assess its relationship with prognosis and disease progression.
      A microRNA (miRNA) microarray and bioinformatics approach were used to identify
      microRNA regulators of CD147 through measurement of the expression and functions
      of these miRNAs in TC tissues and cell lines. Precursor miRNA-transfected cells
      were used to assess regulation of CD147 by miRNA. The effect of miRNA on TC cells
      via inhibition of glycolysis through CD147 targeting was also evaluated. RESULTS:
      We found that miR-125a-5p regulates CD147 and is negatively correlated with its
      expression and function. Moreover, CD147 knockdown or increased miR-125a-5p
      expression significantly reduced the viability, migration, and invasion of TC
      cells. Our mechanistic studies demonstrate that, through directly repressing the
      expression of the CD147 protein, miR-125a-5p suppresses aerobic glycolysis and
      lactate production and subsequently reduces TC cell viability, migration, and
      invasion, thereby exerting tumor suppressor functions. CONCLUSIONS: The novel
      connection identified between miR-125a-5p and CD147 suggests a new diagnostic and
      prognostic role for miR-125a-5p and that CD147 inhibition may be a candidate
      therapeutic target in the therapy of for TC.

PMID- 29634400
TI  - Assessment of Oropharyngeal and Laryngeal Cancer Treatment Delay in a Private and
      Safety Net Hospital System.
AB  - Objective To examine the impact of treatment setting and demographic factors on
      oropharyngeal and laryngeal cancer time to treatment initiation (TTI). Study
      Design Retrospective case series. Setting Safety net hospital and adjacent
      private academic hospital. Subjects and Methods Demographic, staging, and
      treatment details were retrospectively collected for 239 patients treated from
      January 1, 2014, to June 30, 2016. TTI was defined as days between diagnostic
      biopsy and initiation of curative treatment (defined as first day of radiotherapy
      [RT], surgery, or chemotherapy). Results On multivariable analysis, safety net
      hospital treatment (vs private academic hospital treatment), initial diagnosis at
      outside hospital, and oropharyngeal cancer (vs laryngeal cancer) were all
      associated with increased TTI. Surgical treatment, severe comorbidity, and both
      N1 and N2 status were associated with decreased TTI. Conclusion Safety net
      hospital treatment was associated with increased TTI. No differences in TTI were
      found when language spoken and socioeconomic status were examined in the overall
      cohort.

PMID- 29634402
TI  - Mental Imagery Induces Cross-Modal Sensory Plasticity and Changes Future Auditory
      Perception.
AB  - Can what we imagine in our minds change how we perceive the world in the future?
      A continuous process of multisensory integration and recalibration is responsible
      for maintaining a correspondence between the senses (e.g., vision, touch,
      audition) and, ultimately, a stable and coherent perception of our environment.
      This process depends on the plasticity of our sensory systems. The so-called
      ventriloquism aftereffect-a shift in the perceived localization of sounds
      presented alone after repeated exposure to spatially mismatched auditory and
      visual stimuli-is a clear example of this type of plasticity in the audiovisual
      domain. In a series of six studies with 24 participants each, we investigated an
      imagery-induced ventriloquism aftereffect in which imagining a visual stimulus
      elicits the same frequency-specific auditory aftereffect as actually seeing one.
      These results demonstrate that mental imagery can recalibrate the senses and
      induce the same cross-modal sensory plasticity as real sensory stimuli.

PMID- 29634401
TI  - Modulation of mRNA Translation and Cell Viability by Influenza A Virus Derived
      Nonstructural Protein 1.
AB  - Translation of in vitro transcribed messenger RNA (mRNA) is known to be
      compromised by cell's innate immune responses. Herein we show that when mRNA
      encoding nonstructural protein 1 (NS1), an immune evasion gene derived from
      influenza A virus, is co-delivered with mRNA encoding green fluorescent protein
      (GFP), higher GFP expression can be observed in four different interferon
      competent cell types within 6 h, indicating NS1's wide host range property and
      rapid counter response to the cells' innate immune response. Enhanced mRNA
      translation correlates with reduced interferon production in all tested cell
      types and substituting a small portion of luciferase mRNA with NS1 mRNA enhances
      luciferase production compared to the same dose composing of only luciferase mRNA
      although in a cell type specific manner. Toxicity caused by transfection of
      unmodified mRNA is mitigated with the delivery of NS1 mRNA and is observed only
      in NS1 without cleavage and polyadenylation specificity factor 30 kda (CPSF30)
      inhibition function. Conversely, delivery of mRNA encoding NS1 with CPSF30
      inhibition function aggravated toxicity. Overall, we demonstrate that NS1
      enhanced mRNA transfection through active evasion of innate immune responses and
      modulated cellular viability during mRNA transfection.

PMID- 29634403
TI  - Influence of UV dose on the UV/H2O2 process for the degradation of carbamazepine
      in wastewater.
AB  - This study evaluates the influence of UV dose on degradation of carbamazepine
      (CBZ) in wastewater under UV-C (lambda = 254 nm) photolysis with and without
      H2O2. The rate of degradation of CBZ exhibited a direct dependence on the
      intensity of incident UV irradiation as the rate of degradation was observed to
      increase linearly (R2 = 0.98) with UV intensity between 1.67 and 8.95 * 1017
      photons/s. More than 95% of the CBZ that spiked in wastewater rapidly degraded
      within 4 min with a first-order rate constant of 1.2 min-1 for an optimum H2O2
      dose of 100 mg/L. Bench-scale continuous flow reactor experiments also showed
      that CBZ degraded with first-order kinetics at a rate constant of 1.02 min-1. The
      kinetic parameters obtained for a continuous bench-scale reactor were in good
      agreement with the relationships developed through batch experiments with only a
      marginal deviation of +/- 6.5%. The relationship between UV intensity and CBZ
      degradation rate obtained in this study was extrapolated to the UV disinfection
      unit of a wastewater treatment plant to predict possible degradation of CBZ
      during UV disinfection. The addition of 100 mg/L of H2O2 to the secondary-treated
      effluent entering the UV disinfection unit is predicted to achieve over 60%
      degradation of CBZ.

PMID- 29634404
TI  - Short- and Long-term Effects of Neuromodulators for Unexplained Chronic Cough.
AB  - Objective To evaluate the short- and long-term effects of tricyclic
      antidepressants (TCAs) and gabapentin in the treatment of unexplained chronic
      cough (UCC). Study Design Prospective cohort. Setting Tertiary care hospital.
      Subjects and Methods Patients seen between July 2016 and March 2017 were included
      following a formal workup and clinical evaluation indicative of UCC. Patients
      were placed on either a TCA (amitriptyline or nortriptyline) or gabapentin.
      Leicester Cough Questionnaire (LCQ) and percentage improvement scores were
      obtained prior to treatment initiation and at 2 and 6 months of neuromodulator
      treatment. A linear mixed model assessed the change in LCQ score between the 2
      treatment time points and baseline scores. Results Twenty-eight patients
      completed a total of 37 neuromodulator trials. Gabapentin demonstrated
      statistically significant improvement in LCQ scores at 2 months (2.48 points, P<=
      .01) and 6 months (5.40 points, P = .01) of treatment as compared with baseline.
      Patients taking TCAs demonstrated statistically significant improvement of LCQ
      scores at 2 months of treatment (3.46 points, P<= .01). However, the majority of
      patients discontinued treatment, most commonly secondary to the development of
      tachyphylaxis after 2 months, precluding analysis at 6 months. Conclusion While
      both neuromodulator classes demonstrated short-term benefit, the majority of
      patients discontinue treatment prior to 6 months, with patients taking TCAs
      discontinuing more frequently than patients on gabapentin. Future investigations
      are warranted evaluating tachyphylaxis and the utility of dual treatment
      therapies designed to address peripheral and central sensory pathways involved in
      UCC.

PMID- 29634405
TI  - Social priming modulates the neural response to ostracism: a new exploratory
      approach.
AB  - The present study sought to evaluate whether social priming modulates neural
      responses to ostracism, such that making arbitrary interpersonal decisions
      increases the experience of social exclusion more than making arbitrary physical
      decisions. This exploratory event-related potential (ERP) study utilized the
      Lunchroom task, in which adults (N = 28) first selected one of two options that
      included either interpersonal or physical descriptors. Participants then received
      ostracism outcome feedback within a lunchroom scenario in which they were either
      excluded (e.g. sitting alone) or included (e.g. surrounded by others). While the
      N2 component was sensitive to priming decision condition, only the P3 component
      discriminated between ostracism decisions. Further inspection of the neural
      sources indicated that the amygdala, anterior cingulate cortex, and superior
      temporal gyrus were more engaged for exclusion than inclusion conditions during
      both N2 and P3 temporal windows. Evaluation of temporal source dynamics suggest
      that the effects of ostracism are predominant between 250-500 ms and were larger
      following interpersonal than physical decisions. These results suggest that being
      ostracized evokes a larger neural response that is modulated following priming of
      the social brain.

PMID- 29634406
TI  - Key process parameters involved in the treatment of olive mill wastewater by
      membrane bioreactor.
AB  - The Olive Mill Wastewater (OMWW) biodegradation in an external ceramic membrane
      bioreactor (MBR) was investigated with a starting acclimation step with a
      Ultrafiltration (UF) membrane (150 kDa) and no sludge discharge in order to
      develop a specific biomass adapted to OMWW biodegradation. After acclimation
      step, UF was replaced by an Microfiltration (MF) membrane (0.1 um). Sludge
      Retention Time (SRT) was set around 25 days and Food to Microorganisms ratio
      (F/M) was fixed at 0.2 kgCOD kgMLVSS-1 d-1. At stable state, removal of the main
      phenolic compounds (hydroxytyrosol and tyrosol) and Chemical Oxygen Demand (COD)
      were successfully reached (95% both). Considered as a predominant fouling factor,
      but never quantified in MBR treated OMWW, Soluble Microbial Products (SMP)
      proteins, polysaccharides and humic substances concentrations were determined
      (80, 110 and 360 mg L-1 respectively). At the same time, fouling was easily
      managed due to favourable hydraulic conditions of external ceramic MBR.
      Therefore, OMWW could be efficiently and durably treated by an MF MBR process
      under adapted operating parameters.

PMID- 29634407
TI  - Hand Switching Costs are not Uniform Across Response Components.
AB  - We investigated the extent to which a complex finger sequence impacts on hand
      switching costs in a sequential action. Response component latencies (premotor,
      motor, and movement) were compared in no-switch (same finger performed the action
      of pressing and reaching) and switch conditions (pressing with one finger and
      completing the reaching action with the homologous finger from the other hand).
      Results showed that the switch condition presented longer latency for premotor
      and movement components. For the motor component, however, switch condition was
      faster. This expands the previous literature investigating switching costs using
      simple finger movements in more complex tasks. A mechanical explanation of the
      interplay between response subcomponents is provided to explain the inversion of
      response pattern for the motor component.

PMID- 29634408
TI  - Mice Lacking RIP3 Kinase are not Protected from Acute Radiation Syndrome.
AB  - Exposure to high doses of ionizing radiation can cause lethal injury to normal
      tissue, thus inducing acute radiation syndrome. Acute radiation syndrome is
      caused by depletion of bone marrow cells (hematopoietic syndrome) and irreparable
      damage to the epithelial cells in the gastrointestinal tract (gastrointestinal
      syndrome). Although radiation initiates apoptosis in the hematopoietic and
      gastrointestinal compartments within the first few hours after exposure,
      alternative mechanisms of cell death may contribute to injury in these
      radiosensitive tissues. In this study, we utilized mice lacking a critical
      regulator of necroptosis, receptor interacting protein 3 (RIP3) kinase, to
      characterize the role of RIP3 in normal tissue toxicity after irradiation. Our
      results suggest that RIP3-mediated signaling is not a critical driver of acute
      radiation syndrome.

PMID- 29634409
TI  - Policy responses during the Trump administration to older people's growing
      economic risk exposure.
AB  - Economic risk exposure through increased labor market volatility and growing
      caregiving responsibilities has risen for older Americans. At the same time, key
      protections such as unemployment insurance and Social Security have declined,
      while other protections-particularly in the private market-are limited or
      nonexistent. Social policy can lower the chance of risk exposure and the
      associated costs, especially with respect to unemployment and caregiving. In
      virtually all instances, however, the Trump administration has already moved to
      weaken existing protections. And it has offered either no proposals or very
      limited proposals to increase protections in the private sector As a result, an
      aging population will increasingly face rising economic risks on their own.

PMID- 29634410
TI  - Low Expression of Long Noncoding RNA IRAIN Is Associated with Poor Prognosis in
      Non-M3 Acute Myeloid Leukemia Patients.
AB  - AIMS: Deregulation of the long noncoding RNA IRAIN has been identified in several
      cancers. However, the expression pattern of IRAIN and its clinical implication in
      acute myeloid leukemia (AML) are unknown. The purpose of this study was to
      investigate the expression status of IRAIN and its clinical significance in non
      M3 AML patients. METHODS: Quantitative reverse transcription-polymerase chain
      reaction was performed to examine IRAIN transcript levels in 64 de novo non-M3
      AML patients and 51 healthy controls. The association of IRAIN expression with
      clinicopathological factors was statistically analyzed. RESULTS: Compared with
      the controls, IRAIN was significantly downregulated in non-M3 AML patients (p <
      0.001). The median of IRAIN expression divided the non-M3 AML patients into IRAIN
      low-expressing (IRAINlow) and IRAIN high-expressing (IRAINhigh) groups. The
      IRAINlow group tended to have higher white blood cell count and blast counts and
      had markedly shorter overall survival (OS) and relapse-free survival (RFS) (p =
      0.044 and 0.009, respectively). In addition, patients with refractory response to
      chemotherapies and those with subsequent relapse had lower initial IRAIN
      expression. Multivariate analysis further identified IRAIN transcript levels as
      an independent prognostic factor for both RFS and OS. CONCLUSIONS: Our finding
      suggests that IRAIN transcript levels may be a useful biomarker for the prognosis
      of non-M3 AML patients.

PMID- 29634411
TI  - Collision course? Donald Trump, Paul Ryan, and the fate of Medicare.
AB  - The election of Donald Trump as president of the United States raises questions
      about the future of Medicare. How will Medicare fare under Republican-led
      government? There are several compelling reasons that the Trump administration
      and Congressional Republicans might avoid Medicare reform, including the
      political risks of taking on a popular program, the difficulties the party has
      encountered in trying to dismantle the Patient Protection and Affordable Care Act
      (ACA), the importance of older Americans to the GOP coalition, and President
      Trump's views about Medicare. However, because of fiscal pressures and the
      commitment of Speaker of the House Paul Ryan and other Republicans to entitlement
      reform, the GOP nonetheless could end up attempting to make major changes in
      Medicare. Alternatively, Republican efforts to repeal and undermine the ACA could
      unintentionally enhance the political fortunes of proposals to expand Medicare.
      Consequently, the fate of Medicare during the Trump administration remains highly
      uncertain.

PMID- 29634412
TI  - Developing content for an interprofessional training on fear of cancer recurrence
      (FCR): Key informant interviews of healthcare professionals, researchers and
      cancer survivors.
AB  - BACKGROUND: Growing numbers of cancer survivors are receiving healthcare through
      primary care practitioners, who often lack cancer-specific expertise to
      effectively treat survivors' concerns. Addressing that gap, this study aimed to
      develop content for a training on fear of cancer recurrence (FCR), a common
      concern in survivorship. METHODS: Grounded in naturalistic inquiry, 42 key
      informant interviews were conducted, transcribed, and analyzed for themes.
      Participants were healthcare professionals, researchers, and cancer survivors
      Results: Results included themes ranging from: rich conceptualizations of FCR,
      opportunities and challenges for addressing FCR in healthcare settings,
      interventions to address FCR, and important information to include in a training
      on FCR. CONCLUSIONS: This paper provides content for an interprofessional
      training and highlights the importance of developing trainings for
      interprofessional teams, given identified barriers that physicians face in
      addressing FCR and other psychosocial concerns of survivors in primary care.

PMID- 29634414
TI  - PTPN12 Affects Nasopharyngeal Carcinoma Cell Proliferation and Migration Through
      Regulating EGFR.
AB  - OBJECTIVE: Nasopharyngeal carcinoma (NPC) shows the leading morbidity in
      otorhinolaryngological malignant tumor. It is a common malignancy in China with
      obvious reginal distribution. NPC is a polygenic disease that is affected by
      numerous factors. Protein tyrosine phosphatase nonreceptor type 12 (PTPN12)
      regulates multiple tumor proliferation and development, including breast cancer
      and colon cancer. However, the role of PTPN12 in NPC occurrence and development
      has not been elucidated. PATIENTS AND METHODS: NPC cell line CNE2 was cultured in
      vitro and divided into three groups, including control, empty plasmid, and PTPN12
      groups. PTPN12 mRNA and protein expressions were tested by real-time polymerase
      chain reaction and Western blot. CNE2 cell proliferation was detected by MTT
      assay. Cell migration was determined by wound healing assay. Cell apoptosis was
      evaluated by caspase 3 activity detection. Epidermal growth factor receptor
      (EGFR) expression was assessed by Western blot. RESULTS: PTPN12 plasmid
      transfection increased PTPN12 mRNA and protein expressions, suppressed cell
      proliferation and migration, reduced EGFR level, and enhanced caspase 3 activity
      compared with control and empty plasmid groups (p < 0.05). CONCLUSIONS: PTPN12
      regulates NPC proliferation and migration through negative regulating EGFR. It
      could be treated as a molecular target for NPC diagnosis and prognosis analysis.

PMID- 29634413
TI  - Impact of sociodemographic characteristics on underemployment in a longitudinal,
      nationally representative study of cancer survivors: Evidence for the importance
      of gender and marital status.
AB  - BACKGROUND: We examined the longitudinal association between sociodemographic
      factors and an expanded definition of underemployment among those with and
      without cancer history in the United States. METHODS: Medical Expenditure Panel
      Survey data (2007-2013) were used in multivariable regression analyses to compare
      employment status between baseline and two-year follow-up among adults aged 25-62
      years at baseline (n = 1,614 with and n = 39,324 without cancer). Underemployment
      was defined as becoming/staying unemployed, changing from full to part-time, or
      reducing part-time work significantly. Interaction effects between cancer
      history/time since diagnosis and predictors known to be associated with
      employment patterns, including age, gender/marital status, education, and health
      insurance status at baseline were modeled. RESULTS: Approximately 25% of cancer
      survivors and 21% of individuals without cancer reported underemployment at
      follow-up (p = 0.002). Multivariable analyses indicated that those with a cancer
      history report underemployment more frequently (24.7%) than those without cancer
      (21.4%, p = 0.002) with underemployment rates increasing with time since cancer
      diagnosis. A significant interaction between gender/marital status and cancer
      history and underemployment was found (p = 0.0004). There were no other
      significant interactions. Married female survivors diagnosed >10 years ago
      reported underemployment most commonly (38.7%), and married men without cancer
      reported underemployment most infrequently (14.0%). A wider absolute difference
      in underemployment reports for married versus unmarried women as compared to
      married versus unmarried men was evident, with the widest difference apparent for
      unmarried versus married women diagnosed >10 years ago (18.1% vs. 38.7%).
      CONCLUSION: Cancer survivors are more likely to experience underemployment than
      those without cancer. Longer time since cancer diagnosis and gender/marital
      status are critical factors in predicting those at greatest risk of
      underemployment. The impact of cancer on work should be systematically studied
      across sociodemographic groups and recognized as a component of comprehensive
      survivorship care.

PMID- 29634415
TI  - Current and Future Approaches for Effective Cancer Imaging and Treatment.
AB  - Cancer poses a major health problem, not only due to cancer-related deaths but
      also because of treatment toxicities. This review discusses early diagnosis and
      strategies to overcome treatment difficulties, to facilitate recovery, and
      prevent deaths. Generally, noninvasive techniques such as computed tomography
      (CT), magnetic resonance imaging (MRI), single photon emission computed
      tomography (SPECT) and positron emission computed tomography (PET), and their
      hybrid systems, including SPECT/CT, PET/CT, and PET/MRI, are used in diagnosis of
      cancer. Cancer treatment in clinics still comprises conventional methods such as
      chemotherapy, radiotherapy, and surgery. However, these techniques and methods
      are often inadequate. Therefore, new approaches, including the formulation of
      actively and/or passively targeted nanosized drug delivery systems and combined
      treatment protocols, are being investigated. In this article, conventional cancer
      imaging and treatment are reviewed. In addition, the formulation of nanosized
      systems and their use in cancer treatment are discussed and combined diagnostic
      and therapeutic (theranostic) approach are proposed as additional cancer
      therapies.

PMID- 29634416
TI  - Samsum Ant Venom Exerts Anticancer Activity Through Immunomodulation In Vitro and
      In Vivo.
AB  - Samsum ant venom (SAV) is a rich repertoire of natural compounds with tremendous
      pharmacological properties. The present work explores its antineoplastic activity
      in different cell lines followed by its confirmation in vivo. The cell lines,
      HepG2, MCF-7, and LoVo showed the differential dose-dependent antineoplastic
      effect with an increased level of significant cytokines, including Interleukin
      (IL)-1beta, IL-6, and IL-8 and transcription factor, Nuclear factor-kappa B (NF
      kappaB). However, the venom was more effective on HepG2 and MCF-7 cells than LoVo
      cells. Furthermore, the extract was administered to four groups (n = 8) of rats.
      Group I was taken as a control without any treatment, whereas group II received
      CCl4 (1 mL/kg) for induction of mild hepatoma. Group III was given 100 MUg/kg of
      SAV twice a week for 1 month. Group IV was pretreated with the CCl4 (like group
      II) followed by dosing with SAV (100 MUg/kg) for 2 months as per the authors'
      prestandardized dosing schedule. Intriguingly, the rats of group IV demonstrated
      significant decrease in key cytokines, IL-1beta and IL-6, as well as the
      transcription factors, including Tumor Necrosis Factor-alpha (TNF-alpha), NF
      kappaB, and Inhibitor-kappa B (I-kappaB) as compared with group II. Furthermore,
      increase in IL-10 and First apoptosis signal (FAS) in the same group confirmed
      that SAV induces apoptosis at the given dose through immunomodulation leading to
      enhanced tumor killing in vivo. Hence, SAV has an excellent antineoplastic
      activity that can be directly used to treat certain types of cancer. Moreover,
      study of its ingredients can pave ways to design novel anticancer drugs. However,
      further in-depth investigation is required before its clinical trials.

PMID- 29634417
TI  - 64Cu-Labeled Phosphonate Cross-Bridged Chelator Conjugates of c(RGDyK) for PET/CT
      Imaging of Osteolytic Bone Metastases.
AB  - OBJECTIVE: The goal of this research was to evaluate c(RGDyK) conjugated to
      phosphonate-based cross-bridged chelators using Cu-free click chemistry in the
      4T1 mouse mammary tumor bone metastasis model in comparison with 64Cu-CB-TE2A
      c(RGDyK), which previously showed selective binding to integrin alphavbeta3 on
      osteoclasts. EXPERIMENTAL: Two phosphonate-based cross-bridged chelators (CB
      TE1A1P and CB-TE1K1P) were conjugated to c(RGDyK) through bio-orthogonal strain
      promoted alkyne-azide cycloaddition. In vitro and in vivo evaluation of the 64Cu
      labeled TE1A1P-DBCO-c(RGDyK) (AP-c(RGDyK)), TE1K1P-PEG4-DBCO-c(RGDyK) (KP
      c(RGDyK)), and CB-TE2A-c(RGDyK) were compared in the 4T1 mouse model of bone
      metastasis. The affinities of the unconjugated and chelator-c(RGDyK) analogs for
      alphavbeta3 integrin were determined using a competitive-binding assay. For in
      vivo evaluation, BALB/c mice were injected with 1 * 105 4T1/Luc cells in the left
      ventricle. Formation of metastases was monitored by bioluminescence imaging (BLI)
      followed by small-animal PET/CT 2 h postinjection of radiotracers. RESULTS: The
      chelator-peptide conjugates showed similar affinity to integrin alphavbeta3, in
      the low nM range. PET imaging demonstrated a higher uptake in bones having
      metastases for all 64Cu-labeled c(RGDyK) analogs compared with bones in nontumor
      bearing mice. The correlation between uptake of 64Cu-AP-c(RGDyK) and 64Cu-KP
      c(RGDyK) in bones with metastases based on PET/CT imaging, and osteoclast number
      based on histomorphometry, was improved over the previously investigated 64Cu-CB
      TE2A-c(RGDyK). CONCLUSION: These data suggest that the phosphonate chelator
      conjugates of c(RDGyK) peptides are promising PET tracers suitable for imaging
      tumor-associated osteoclasts in bone metastases.

PMID- 29634419
TI  - Correction to: miR-19-5p Enhances Tumorigenesis in Human Colorectal Cancer Cells
      by Targeting TSPYL5 by Huang, C., and Luo, H. (2018). DNA Cell Biol 37(1), 23-30.
      DOI: 10.1089/dna.2017.3804.

PMID- 29634418
TI  - Demethylation of GFRA4 Promotes Cell Proliferation and Invasion in Hirschsprung
      Disease.
AB  - Hirschsprung disease (HSCR) is congenital intestinal aganglionosis attributed to
      a failure to migrate and survive of neural crest-derived cells. Glial cell
      derived neurotrophic factor alpha 4 (GFRA4) is expressed in the derivatives of
      the neural crest in the enteric nervous system, but whether it is related with
      HSCR still remains unclear. This study was designed to investigate its role and
      epigenetic mechanisms in HSCR in vitro. The expression of GFRA4 mRNA in HSCR
      tissues was determined using quantitative real-time PCR analysis. In this study,
      we found that GFRA4 expression was significantly reduced in HSCR tissues and
      cells through GFRA4 methylation by quantitative real-time PCR analysis,
      methylation-specific PCR, and bisulfite sequencing PCR. DNA methyltransferase
      inhibitor, 5-AzaC, concomitantly upregulated the protein levels of GFRA4, as well
      as DNA methyltransferase1 (DNMT1) and DNMT2 in SH-5YSY cells. Moreover, we found
      upregulated GFRA4 significantly promoted cell proliferation, cell cycle
      progression and invasion, but inhibited apoptosis in SH-5YSY cells, whereas GFRA4
      knockdown caused the opposite effects in SH-5YSY cells by CCK-8, 5-ethynyl-2'
      deoxyuridine (EdU), flow cytometry, and Transwell assays. In conclusion, our
      results support that aberrant CpG hypermethylation at least partly accounts for
      GFRA4 silencing in HSCR, which impairs its protective role in enteric nervous
      system.

PMID- 29634420
TI  - HMGA1 Mediated High-Glucose-Induced Vascular Smooth Muscle Cell Proliferation in
      Diabetes Mellitus: Association Between PI3K/Akt Signaling and HMGA1 Expression.
AB  - High-mobility group protein A1 (HMGA1), an architectural transcription factor,
      was found to regulate multiple gene expression in mammals. Recent studies firmly
      indicate an association between HMGA1 and type 2 diabetes. However, the presence
      and function of HMGA1 in diabetic vasculopathy has not been substantiated. in
      this study, we first determined the HMGA1 changes in aorta tissue of diabetic
      rats. In streptozotocin-induced diabetic rats, a higher level of blood glucose
      and plasma lipids, an increase of intima-media thickness, and a significant
      upregulation and accumulation of HMGA1, mainly in the nucleus and around the
      nuclear membrane of vascular smooth muscle cells (VSMCs), were detected. In
      vitro, high glucose increased HMGA1 expression and promoted proliferation of
      VSMCs, which could be blunted by Wortmannin and LY294002, inhibitors of PI3K/Akt
      pathway, and specificity protein 1 (SP1) siRNA. Moreover, knockdown of HMGA1
      could weaken the upregulation of cyclin D1 accompanied by high-glucose-induced
      HMGA1 in VSMCs. Taken together, these findings demonstrate the vital role of
      PI3K/Akt-SP1-HMGA1 pathway in high-glucose-induced VSMCs proliferation.

PMID- 29634421
TI  - Protein O-Glucosyltransferase 1 Expression Influences Formation of Differentiated
      Myotubes in C2C12 Cell Line.
AB  - The protein O-glucosyltransferase 1 (Poglut1) links O-glucose to epidermal growth
      factor-like repeats harboring the C1XSX(P/A)C2 consensus sequence. Poglut1 is a
      ubiquitous endoplasmic reticulum-resident protein largely found in metazoans, but
      only about 50 proteins possess this consensus sequence. Among them, Notch
      receptors have multiple O-glucosylation sites and their activation depends on
      this status. In adult skeletal muscle, Notch signaling contributes to the
      maintenance of satellite cell (SC) quiescence and the proliferation of myoblasts
      after SC activation. To address the role of Poglut1 in myogenesis, we created two
      stable C2C12 cell lines where Poglut1 was downexpressed by 42% and 81%, and
      assessed their ability to differentiate. We showed that Poglut1 knockdown reduced
      Notch signaling and largely affected the key regulators of myogenic
      differentiation, with PAX7 decrease and MYOD increase. This perturbed Pax7/MyoD
      expression balance led to a premature myogenic differentiation and an increase in
      myotube size, accentuated in case of strong Poglut1 downexpression. Differences
      observed between myotubes of the two Poglut1 knockdown cell lines could reflect
      dissimilar fusion defects. We concluded that Poglut1 contributes to myogenesis by
      regulating Notch signaling and defining, directly or indirectly, the proportion
      of cells that commit differentiation.

PMID- 29634422
TI  - The Trump Administration's assault on health and social programs: potential
      consequences for older Hispanics.
AB  - Health and social welfare policy proposals put forth by the Trump administration
      and Republican-controlled Congress could have huge impacts on low-income groups.
      This paper focuses on older Hispanics, with an emphasis on the Mexican-origin
      population who form the largest Hispanic subgroup. A demographic portrait is
      presented that indicates that Mexican-origin individuals have less wealth and
      lower incomes than do non-Hispanic Whites. Given rising health care costs, lower
      use of nursing homes, and greater propensity to live with grown children,
      prevailing economic disadvantage has serious consequences for this population.
      More restrictive immigration policies aimed at limiting family reunification
      could have intergenerational caregiving consequences. In addition, because of
      labor-force disadvantages, low-income Mexican-origin adults are less likely to
      have private insurance compared to non-Hispanic Whites as they approach
      retirement. Consequently, Mexican-origin older adults tend to rely on Medicaid
      when eligible; in contrast, late-life migrants-who do not qualify for federally
      funded benefits for at least five years-and unauthorized migrants-who are
      excluded from federally funded benefits-have extremely limited access to safety
      net provisions. The potential effects of proposed cutbacks in health care
      financing on older Hispanics are discussed.

PMID- 29634423
TI  - Morphologically Cryptic Species of the Astyanax bimaculatus "Caudal Peduncle
      Spot" Subgroup Diagnosed Through Cytogenetic Characters.
AB  - Astyanax is a species-rich polyphyletic genus distributed between the southern
      United States and central Argentina. The genus contains groups of cryptic
      species, which are difficult to distinguish, and are sometimes identified
      wrongly. Basic and molecular cytogenetic analyses were run on Astyanax abramis
      and three junior synonyms of Astyanax lacustris: Astyanax altiparanae, from the
      upper Parana River basin, Astyanax asuncionensis, from the lower Parana basin,
      and Astyanax jacuhiensis, from the upper Uruguay River. These species all belong
      to the Astyanax bimaculatus group. All species presented 2n = 50 chromosomes and
      single nucleolar organizing regions (NORs). In A. altiparanae, the karyotype was
      6m + 28sm+4st+12a and the NORs were present in pair 20, while A. jacuhiensis was
      8m + 28sm+6st+8a, with NORs in pair 22, and A. asuncionensis was 8m +
      24sm+6st+12a, with NORs in pair 20. A. abramis was 4m + 30sm+8st+8a with NORs in
      pair 22. Fluorescence in situ hybridization revealed single 5S rDNA cistrons in
      A. altiparanae and A. asuncionensis, and multiple (4) cistrons in A. abramis and
      A. jacuhiensis. Heterochromatin had a distinct distribution in each species, but
      was predominantly centromeric and interstitial proximal. In A. abramis and A.
      asuncionensis, the first acrocentric chromosome pair presented centromeric,
      telomeric, and interstitial-proximal heterochromatin in the long arm, which may
      represent the presence of homologous chromosomes in these species. While there
      are some cytogenetic similarities, differences in the location of 5S rDNA,
      distribution of heterochromatin, and karyotype formulae contribute to the
      differentiation of the study species, and support the identification of
      phylogenetically proximate groups in the "Astyanax clade."

PMID- 29634424
TI  - Financing long-term services and supports: challenges, goals, and needed reforms.
AB  - The need for long-term services and supports (LTSS) presents a growing financial
      burden on disabled individuals, their families, and state Medicaid budgets.
      Strategies for addressing this problem pose both a policy design and a political
      challenge. This article begins by explaining the choices and trade-offs policy
      makers face in designing new policy and offers the outlines of a specific
      approach to navigating these. It then concludes with an assessment of current
      LTSS policy directions and politics-specifically, the movement to constrain,
      rather than enhance, federal financing for LTSS and the counterpressures
      necessary to strengthen meaningful insurance protection. While the political
      environment has become even less conducive to expansion of public benefits, the
      underlying problem of LTSS financing will grow and persist. And politics change.
      Thus, in this paper we offer and explain the choices we would make to bridge the
      political divide-specifically, a proposal to develop a new public-private
      partnership based on a public program to cover "back-end" or catastrophic costs
      plus measures making private insurance more attractive for the "up-front" risk,
      an approach that has recently been endorsed by a number of bipartisan groups.

PMID- 29634425
TI  - Using ecological momentary assessment to examine the relationship between craving
      and affect with opioid use in a clinical trial of clonidine as an adjunct
      medication to buprenorphine treatment.
AB  - BACKGROUND: In a recent clinical trial (NCT00295308), we demonstrated that
      clonidine decreased the association between opioid craving and moderate levels of
      stress and affect in patients receiving buprenorphine-based opioid agonist
      therapy. OBJECTIVES: To examine the relationship between illicit opioid use and
      craving and affect during the evaluation of clonidine as an adjunct medication in
      buprenorphine treatment for opioid use disorder. Secondarily, to examine whether
      those relationships are driven by within- or between-participant factors.
      METHODS: This was a secondary data analysis from our original trial. Participants
      (N = 108, female: n = 23, male n = 85) receiving buprenorphine were randomized to
      receive adjunct clonidine or placebo. Participants used portable electronic
      devices to rate stress, mood, and craving via ecological momentary assessment
      (EMA) four times randomly each day. To associate the EMA data with illicit opioid
      use, each EMA report was linked to participants' next urine drug screen (thrice
      weekly). We used generalized linear mixed models to examine the interaction
      between treatment group and illicit opioid use, as well as to decompose the
      analysis into within- and between-participant effects. RESULTS: Craving for
      opioids and cocaine was increased when participants were using illicit opioids;
      this effect was greater in the clonidine group. For affect, mood was poorer
      during periods preceding opioid-positive urines than opioid-negative urines for
      clonidine-treated participants, whereas there was no difference for placebo
      participants. CONCLUSION: This secondary analysis provides evidence that for
      participants maintained on opioid agonist therapy, clonidine minimized the
      behavioral impact of moderate levels of negative affect and craving.

PMID- 29634427
TI  - Sleep Quality, Fatigue, and Quality of Life Among Teenage and Young Adult Cancer
      Survivors.
AB  - PURPOSE: Teenage and young adult (TYA) cancer survivors experience a range of
      health-related problems during and beyond the active treatment period. This study
      examined associations between fatigue, sleep quality, and health-related quality
      of life (HRQOL) among TYA survivors. METHODS: Self-reported data on sleep quality
      (Pittsburgh Sleep Quality Index), fatigue (Functional Assessment of Chronic
      Illness Therapy Fatigue), and HRQOL (EuroQoL-5) were gathered from United Kingdom
      TYA survivors between 13 and 24 years of age. TYA survivors were stratified into
      those on (n = 67) and off (n = 135) treatment. Linear regression analyses were
      used with HRQOL as the dependent variable to investigate potential associations.
      Fatigue and sleep were entered separately and together in the same model. Age at
      survey and diagnosis, gender, and ethnicity were included as covariates. RESULTS:
      85.07% of TYAs on and 62.69% of TYAs off treatment had sleep quality scores
      suggestive of clinically significant sleep disorders. 56.72% of TYAs on and
      26.67% of TYAs off treatment reported clinically significant levels of fatigue.
      Strong independent associations between sleep (B = 0.05, 95% confidence intervals
      [CI] = 0.03-0.07, p < 0.001), fatigue (B = 0.02, 95% CI = 0.01-0.03, p < 0.001),
      and HRQOL were observed among TYA survivors on treatment. TYAs off treatment
      showed moderate to strong associations between sleep (B = 0.04, 95% CI = 0.02
      0.05, p < 0.001) and fatigue (B = 0.02, 95% CI = 0.01-0.02, p < 0.001), and
      HRQOL, when examined separately. Sleep was not independently associated with
      HRQOL among TYAs off treatment (B = 0.01, 95% CI = -0.01 to 0.02, p = 0.296).
      CONCLUSION: The significant associations reported suggest that sleep quality and
      fatigue are potential modifiable factors associated with HRQOL. Further research
      is warranted to understand the direction of associations.

PMID- 29634426
TI  - Potential roles of tumor-derived exosomes in angiogenesis.
AB  - INTRODUCTION: Tumor-derived exosomes (TEX) and their role in tumor progression by
      accelerating angiogenesis are of great current interest. A better understanding
      of the mechanisms underlying TEX-blood vessels cross-talk may lead to
      improvements in current diagnosis, prognosis and treatment of cancer. Areas
      covered: For solid tumors, an adequate blood supply is of critical importance for
      their development, growth and metastasis. TEX, virus-size vesicles which
      circulate freely throughout body fluids and accumulate in the tumor
      microenvironment (TME), have been recognized as a new contributor to
      angiogenesis. TEX serve as a communication system between the tumor and various
      normal cells and are responsible for functional reprogramming of these cells. The
      molecular and genetic cargos that TEX deliver to the recipient cells involved in
      angiogenesis promote its induction and progression. The targeted inhibition of
      TEX pro-angiogenic functions might be a novel therapeutic approach for control of
      tumor progression. Expert opinion: TEX circulating in body fluids of cancer
      patients carry a complex molecular and genetic cargo and are responsible for
      phenotypic and functional reprogramming of endothelial cells and other normal
      cells residing in the TME.

PMID- 29634428
TI  - Patellar Fractures.

PMID- 29634429
TI  - Racial Inequalities in Oral Health.
AB  - Together with other social categories, race has been at the core of much
      scholarly work in the area of humanities and social sciences, as well as a host
      of applied disciplines. In dentistry, debates have ranged from the use of race as
      a criterion for the recommendation of specific dental procedures to a means of
      assessing inequalities in a variety of outcomes. What is missing in these
      previous discussions, though, is a broader understanding of race that transcends
      relations with genetic makeup and other individual-level characteristics. In this
      review, we provide readers with a critique of the existing knowledge on race and
      oral health by answering the following 3 guiding questions: (1) What concepts and
      ideas are connected with race in the field of dentistry? (2) What can be learned
      and what is absent from the existing literature on the topic? (3) How can we
      enhance research and policy on racial inequalities in oral health? Taken
      together, the reviewed studies rely either on biological distinctions between
      racial categories or on other individual characteristics that may underlie racial
      disparities in oral health. Amidst a range of individual-level factors, racial
      inequalities have often been attributed to lower socioeconomic status and "health
      damaging" cultural traits, for instance, patterns of and reasons for dental
      visits, dietary habits, and oral hygiene behaviors. While this literature has
      been useful in documenting large and persistent racial gaps in oral health, wider
      sociohistorical processes, such as systemic racism, as well as their
      relationships with economic exploitation, social stigmatization, and political
      marginalization, have yet to be operationalized among studies on the topic. A
      nascent body of research has recently begun to address some of these factors, but
      limited attention to structural theories of racism means that many more studies
      are needed to effectively mitigate racial health differentials.

PMID- 29634431
TI  - Cancer Incidence in Adolescents and Young Adults in 24 Selected Populations of
      Latin America.
AB  - OBJECTIVE: Describe incidence rates for the most common cancers in Latin American
      adolescents and young adults (AYA). METHODS: Incidence data were extracted from
      the Cancer Incidence in Five Continents series, available online (IARC). Age
      standardized incidence rates and trend analysis were calculated. Trends were
      calculated by joinpoint regression analysis to obtain average annual percentage
      change values. RESULTS: There were 22,990 invasive incident cancer cases in AYA
      between 1998 and 2007, obtained from 24 population-based cancer registries. The
      most common cancer in males was gonadal germ cell tumor, with incidence rates
      ranging from 1.7 to 7.0/100,000; in females the most common cancer was thyroid
      cancer, with rates ranging from 0.9 to 10.0/100,000. Incidence trends were
      limited to four regional populations and increased for all malignancies, in males
      from 1.8% to 3.4% and in females from 0.9% to 1.8%. CONCLUSIONS: Cancer incidence
      rates in Latin American AYA are low. There are few PBCRs with long-term data, and
      therefore, the results herein presented are a partial view of cancer in Latin
      American AYA populations.

PMID- 29634432
TI  - Differential Gene Expression and Pathway Analysis in Juvenile Nasopharyngeal
      Angiofibroma Using RNA Sequencing.
AB  - Juvenile nasopharyngeal angiofibroma (JNA) is a highly vascularized and locally
      aggressive tumor that typically presents in adolescent males. The molecular
      biology of this tumor remains understudied. We sought to identify differentially
      expressed genes in the JNA transcriptome through messenger RNA sequencing of
      primary fibroblasts from 2 tumor explants and tonsil tissue from tumor-free
      subjects. In total, 1088 significant, differentially expressed genes were
      identified with 749 upregulated and 339 downregulated. Pathway analysis
      identified a number of activated signaling pathways, most notably, the vascular
      endothelial growth factor (VEGF) pathway (adjusted overlap P = .03). VEGF-A
      showed a 4.4-fold upregulation in JNA samples. In addition, the angiogenic
      receptor, fibroblast growth factor receptor 2 (FGFR2), was not present in tumor
      free samples but increased in JNA. We validate these findings with
      immunohistochemistry, demonstrating upregulation of VEGF and FGFR2 in patient
      sections. Inhibition of the VEGF or FGFR signaling axes may have therapeutic
      potential in the treatment of JNA.

PMID- 29634430
TI  - Linear pharmacokinetic parameters for monoclonal antibodies are similar within a
      species and across different pharmacological targets: A comparison between human,
      cynomolgus monkey and hFcRn Tg32 transgenic mouse using a population-modeling
      approach.
AB  - The linear pharmacokinetics (PK) of therapeutic monoclonal antibodies (mAbs) can
      be considered a class property with values that are similar to endogenous IgG.
      Knowledge of these parameters across species could be used to avoid unnecessary
      in vivo PK studies and to enable early PK predictions and
      pharmacokinetic/pharmacodynamic (PK/PD) simulations. In this work, population
      pharmacokinetic (popPK) modeling was used to determine a single set of 'typical'
      popPK parameters describing the linear PK of mAbs in human, cynomolgus monkey and
      transgenic mice expressing the human neonatal Fc receptor (hFcRn Tg32), using a
      rich dataset of 27 mAbs. Non-linear PK was excluded from the datasets and a 2
      compartment model was applied to describe mAb disposition. Typical human popPK
      estimates compared well with data from comparator mAbs with linear PK in the
      clinic. Outliers with higher than typical clearance were found to have non
      specific interactions in an affinity-capture self-interaction nanoparticle
      spectroscopy assay, offering a potential tool to screen out these mAbs at an
      early stage. Translational strategies were investigated for prediction of human
      linear PK of mAbs, including use of typical human popPK parameters and allometric
      exponents from cynomolgus monkey and Tg32 mouse. Each method gave good prediction
      of human PK with parameters predicted within 2-fold. These strategies offer
      alternative options to the use of cynomolgus monkeys for human PK predictions of
      linear mAbs, based on in silico methods (typical human popPK parameters) or using
      a rodent species (Tg32 mouse), and call into question the value of completing
      extensive in vivo preclinical PK to inform linear mAb PK.

PMID- 29634434
TI  - Comparative removal of emerging contaminants from aqueous solution by adsorption
      on an activated carbon.
AB  - Batch sorption experiments were performed to study the adsorption of six emerging
      pollutants from aqueous solutions using a commercial granular activated carbon as
      adsorbent. Caffeine, clofibric acid, diclofenac, gallic acid, ibuprofen and
      salicylic acid were selected as representative contaminants. The activated carbon
      was characterized by nitrogen adsorption at 77 K, and through the determination
      of point of zero charge. The effects of several operational parameters, such as
      pH, initial concentration of organic molecules, mass of adsorbent and contact
      time, on the sorption behaviour were evaluated. The contact time to attain
      equilibrium for maximum adsorption was found to be 40 min. The kinetic data were
      correlated to several adsorption models, and the adsorption mechanism found to
      follow pseudo-second-order and intraparticle-diffusion models with external mass
      transfer predominating in the first 15 min of the experiment. The equilibrium
      adsorption data were analysed using the Freundlich, Langmuir and Toth isotherm
      equation models. The similar chemical structure and molecular weight of the
      organic pollutants studied to make the adsorption capacity of the activated
      carbon used very similar for all the molecules.

PMID- 29634435
TI  - LI-RADS for MR Imaging Diagnosis of Hepatocellular Carcinoma: Performance of
      Major and Ancillary Features.
AB  - Purpose To evaluate the performance of major features, ancillary features, and
      categories of Liver Imaging Reporting and Data System (LI-RADS) version 2014 at
      magnetic resonance (MR) imaging for the diagnosis of hepatocellular carcinoma
      (HCC). Materials and Methods This retrospective institutional review board
      approved study included patients with liver MR imaging and at least one
      pathologically proved lesion. Between 2004 and 2016, 102 patients (275
      observations including 113 HCCs) met inclusion criteria. Two radiologists
      independently assessed major and ancillary imaging features for each liver
      observation and assigned a LI-RADS category. Per-lesion estimates of diagnostic
      performance of major features, ancillary features, and LI-RADS categories were
      assessed by using generalized estimating equation models. Results Major features
      (arterial phase hyperenhancement, washout, capsule, and threshold growth) had a
      sensitivity of 88.5%, 60.6%, 32.9%, and 41.6%, and a specificity of 18.6%, 84.8%,
      98.8%, and 83.2% for HCC, respectively. Ancillary features (mild-moderate T2
      hyperintensity, restricted diffusion, mosaic architecture, intralesional fat,
      lesional fat sparing, blood products, and subthreshold growth) had a sensitivity
      of 62.2%, 54.8%, 9.9%, 30.9%, 23.1%, 2.8%, and 48.3%, and a specificity of 79.4%,
      90.6%, 99.4%, 94.2%, 83.1%, 99.3%, and 91.4% for HCC, respectively. The LR-5 or
      LR-5 V categories had a per-lesion sensitivity of 50.8% and a specificity of
      95.8% for HCC, respectively. The LR-4, LR-5, or LR-5 V categories (determined by
      using major features only vs combination of major and ancillary features) had a
      per-lesion sensitivity of 75.9% and 87.9% and a per-lesion specificity of 87.5%
      and 86.2%, respectively. Conclusion The use of ancillary features in combination
      with major features increases the sensitivity while preserving a high specificity
      for the diagnosis of HCC.

PMID- 29634436
TI  - Radiation Dose Reduction by Using CT with Iterative Model Reconstruction in
      Patients with Pulmonary Invasive Fungal Infection.
AB  - Purpose To compare the diagnostic quality of reduced radiation dose computed
      tomography (CT) with iterative model reconstruction (IMR) versus that of
      conventional low-dose CT in patients with pulmonary invasive fungal infection.
      Materials and Methods This prospective observational study included 48 patients
      (mean age +/- standard deviation, 39.9 years +/- 11.3) known to have or suspected
      of having pulmonary invasive fungal infection between October 2016 and July 2017.
      Patients underwent CT with IMR (at 80 kV with 20 mA) immediately after low-dose
      CT (at 80 kV with automatic exposure control). Images were reconstructed by using
      a hybrid iterative reconstruction (HIR) algorithm and IMR. Two radiologists
      independently assessed subjective image quality, noise, and visibility of normal
      and abnormal findings by using a five-point scale. Objective measurements,
      including image noise, contrast-to-noise ratio (CNR), and corresponding figure of
      merit (FOM), were compared by using repeated-measures analysis of variance with
      Bonferroni post hoc tests for multiple comparisons. Results The mean effective
      dose was 0.3 mSv +/- 0.3 for CT with IMR and 0.7 mSv +/- 0.2 for low-dose CT (P <
      .01). When the image noise and CNR were normalized to the effective dose, CT
      images obtained with IMR had significantly higher FOM than did other image series
      (P < .0001). Subjectively, visibility of CT features of invasive fungal infection
      on CT scans reconstructed with IMR was rated as noninferior to that on low-dose
      CT scans reconstructed with HIR, except for the halo sign. Conclusion CT with IMR
      had approximately 60% dose reduction compared with conventional low-dose CT, with
      reduced noise and improved depiction of abnormal findings, in patients with
      pulmonary invasive fungal infection.

PMID- 29634437
TI  - Risk Estimation for Biliary Atresia in Patients with Neonatal Cholestasis:
      Development and Validation of a Risk Score.
AB  - Purpose To develop and validate a scoring system based on clinical and imaging
      features to predict the risk for biliary atresia in patients with neonatal
      cholestasis. Materials and Methods Patients with neonatal cholestasis who
      underwent both ultrasonography (US) and hepatobiliary scintigraphy (n = 480) were
      retrospectively identified from two tertiary referral hospitals from January 2000
      to February 2017. Patients from one hospital were classified as the derivation
      cohort (n = 371), and those from the other hospital were classified as the
      validation cohort (n = 109). Clinical and imaging features associated with
      biliary atresia were assessed. Histopathologic or intraoperative cholangiographic
      findings served as the reference standard for biliary atresia. A prediction model
      was developed by using logistic regression and was then transformed into a
      scoring system. The scoring system was internally and externally validated.
      Results Among the 371 patients in the derivation cohort, 97 (26.15%) had biliary
      atresia. A scoring system was constructed with the following variables: full-term
      birth, presence of the triangular cord sign at US, abnormal gallbladder
      morphology at US, and failure of radioisotope excretion to the small bowel at
      hepatobiliary scintigraphy. The maximum possible score with this system is 7
      points. This system enabled differentiation of biliary atresia in the derivation
      cohort (C statistic, 0.981; 95% confidence interval [CI]: 0.970, 0.992) and the
      validation cohort (C statistic, 0.995; 95% CI: 0.987, 1.000). The risk score also
      showed good calibration in both the derivation and the validation cohorts (P =
      .328 and P = .281, respectively). Conclusion A simple scoring system combining
      clinical and imaging features can help accurately estimate the risk for biliary
      atresia in patients with neonatal cholestasis.

PMID- 29634438
TI  - Coronary CT Angiography-derived Fractional Flow Reserve: Machine Learning
      Algorithm versus Computational Fluid Dynamics Modeling.
AB  - Purpose To compare two technical approaches for determination of coronary
      computed tomography (CT) angiography-derived fractional flow reserve (FFR)-FFR
      derived from coronary CT angiography based on computational fluid dynamics
      (hereafter, FFRCFD) and FFR derived from coronary CT angiography based on machine
      learning algorithm (hereafter, FFRML)-against coronary CT angiography and
      quantitative coronary angiography (QCA). Materials and Methods A total of 85
      patients (mean age, 62 years +/- 11 [standard deviation]; 62% men) who had
      undergone coronary CT angiography followed by invasive FFR were included in this
      single-center retrospective study. FFR values were derived on-site from coronary
      CT angiography data sets by using both FFRCFD and FFRML. The performance of both
      techniques for detecting lesion-specific ischemia was compared against visual
      stenosis grading at coronary CT angiography, QCA, and invasive FFR as the
      reference standard. Results On a per-lesion and per-patient level, FFRML showed a
      sensitivity of 79% and 90% and a specificity of 94% and 95%, respectively, for
      detecting lesion-specific ischemia. Meanwhile, FFRCFD resulted in a sensitivity
      of 79% and 89% and a specificity of 93% and 93%, respectively, on a per-lesion
      and per-patient basis (P = .86 and P = .92). On a per-lesion level, the area
      under the receiver operating characteristics curve (AUC) of 0.89 for FFRML and
      0.89 for FFRCFD showed significantly higher discriminatory power for detecting
      lesion-specific ischemia compared with that of coronary CT angiography (AUC,
      0.61) and QCA (AUC, 0.69) (all P < .0001). Also, on a per-patient level, FFRML
      (AUC, 0.91) and FFRCFD (AUC, 0.91) performed significantly better than did
      coronary CT angiography (AUC, 0.65) and QCA (AUC, 0.68) (all P < .0001).
      Processing time for FFRML was significantly shorter compared with that of FFRCFD
      (40.5 minutes +/- 6.3 vs 43.4 minutes +/- 7.1; P = .042). Conclusion The FFRML
      algorithm performs equally in detecting lesion-specific ischemia when compared
      with the FFRCFD approach. Both methods outperform accuracy of coronary CT
      angiography and QCA in the detection of flow-limiting stenosis.

PMID- 29634439
TI  - Double Reading in Breast Cancer Screening: Cohort Evaluation in the CO-OPS Trial.
AB  - Purpose To investigate the effect of double readings by a second radiologist on
      recall rates, cancer detection, and characteristics of cancers detected in the
      National Health Service Breast Screening Program in England. Materials and
      Methods In this retrospective analysis, 805 206 women were evaluated through
      screening and diagnostic test results by extracting 1 year of routine data from
      33 English breast screening centers. Centers used double reading of digital
      mammograms, with arbitration if there were discrepant interpretations.
      Information on reader decisions, with results of follow-up tests, were used to
      explore the effect of the second reader. The statistical tests used were the test
      for equality of proportions, the chi2 test for independence, and the t test.
      Results The first reader recalled 4.76% of women (38 295 of 805 206 women; 95%
      confidence interval [CI]: 4.71%, 4.80%). Two readers recalled 6.19% of women in
      total (49 857 of 805 206 women; 95% CI: 6.14%, 6.24%), but arbitration of
      discordant readings reduced the recall rate to 4.08% (32 863 of 805 206 women;
      95% CI: 4.04%, 4.12%; P < .001). A total of 7055 cancers were detected, of which
      627 (8.89%; 95% CI: 8.22%, 9.55%; P < .001) were detected by the second reader
      only. These additional cancers were more likely to be ductal carcinoma in situ
      (30.5% [183 of 600] vs 22.0% [1344 of 6114]; P < .001), and additional invasive
      cancers were smaller (mean size, 14.2 vs 16.7 mm; P < .001), had fewer involved
      nodes, and were likely to be lower grade. Conclusion Double reading with
      arbitration reduces recall and increases cancer detection compared with single
      reading. Cancers detected only by the second reader were smaller, of lower grade,
      and had less nodal involvement. (c) RSNA, 2018.

PMID- 29634440
TI  - Breast Cancer Screening: Two (or Three) Heads Are Better than One?

PMID- 29634441
TI  - Renal Allograft Dysfunction: Evaluation with Shear-wave Sonoelastography.
AB  - Purpose To evaluate whether shear-wave sonoelastography can help differentiate
      stable renal allograft from acute allograft dysfunction and chronic allograft
      dysfunction and to correlate shear-wave sonoelastography measurements with
      resistive index (RI), serum creatinine level, estimated glomerular filtration
      rate (eGFR) obtained with the Nankivell equation, and biopsy findings. Materials
      and Methods A prospective study of 60 patients who had undergone renal
      transplantation was conducted between October 2014 and March 2016. Patients were
      classified as having stable allograft, acute allograft dysfunction, or chronic
      allograft dysfunction on the basis of clinical parameters. Mean parenchymal
      stiffness was compared. The Banff score was used wherever applicable. Receiver
      operating characteristic curves were drawn to evaluate the feasibility of
      differentiation. Results Thirty patients had graft dysfunction (acute in 19
      patients and chronic in 11). Mean parenchymal stiffness values in stable
      allograft, acute allograft dysfunction, and chronic allograft dysfunction were
      8.51 kPa +/- 2.44, 11.06 kPa +/- 2.91, and 24.50 kPa +/- 4.49, respectively
      (stable vs acute dysfunction, P = .010; stable vs chronic dysfunction, P < .001;
      acute sysfunction vs chronic dysfunction, P < .001). The allograft parenchymal
      stiffness values for patients with Banff grade I (mild interstitial fibrosis and
      tubular atrophy) differed significantly from those with Banff grade II (moderate
      interstitial fibrosis and tubular atrophy) (P = .02). Parenchymal stiffness
      showed a negative correlation with eGFR (r = -0.725; P < .001) and a positive
      correlation with RI (r = 0.562; P < .001) and serum creatinine level (r = 0.714;
      P < .001). The sensitivity was 73.68% and specificity was 80% in the
      differentiation of stable graft from acute graft dysfunction (threshold value,
      10.11 kPa). Conclusion Shear-wave sonoelastographic evaluation of renal
      parenchymal stiffness may help differentiate stable allograft from acute and
      chronic allograft dysfunction. The inverse correlation of parenchymal stiffness
      with eGFR and positive correlation with RI and serum creatinine level show that
      shear-wave sonoelastography may reflect functional status of the renal allograft.

PMID- 29634444
TI  - Understanding Fish Linear Acceleration Using an Undulatory Biorobotic Model with
      Soft Fluidic Elastomer Actuated Morphing Median Fins.
AB  - Although linear accelerations are an important common component of the diversity
      of fish locomotor behaviors, acceleration is one of the least-understood aspects
      of propulsion. Analysis of acceleration behavior in fishes with both spiny and
      soft-rayed median fins demonstrates that fin area is actively modulated when fish
      accelerate. We implemented an undulatory biomimetic robotic fish model with
      median fins manufactured using multimaterial three-dimensional printing-a spiny
      rayed dorsal fin, soft-rayed dorsal/anal fins, and a caudal fin-whose stiffnesses
      span three orders of magnitude. We used an array of fluidic elastomeric soft
      actuators to mimic the dorsal/anal inclinator and erector/depressor muscles of
      fish, which allowed the soft fins to be erected or folded within 0.3 s. We
      experimentally show that the biomimetic soft dorsal/anal fin can withstand
      external loading. We found that erecting the soft dorsal/anal fins significantly
      enhanced the linear acceleration rate, up to 32.5% over the folded fin state.
      Surprisingly, even though the projected area of the body (in the lateral plane)
      increased 16.9% when the median fins were erected, the magnitude of the side
      force oscillation decreased by 24.8%, which may have led to significantly less
      side-to-side sway in the robotic swimmer. Visualization of fluid flow in the wake
      of median fins reveals that during linear acceleration, the soft dorsal fin
      generates a wake flow opposite in direction to that of the caudal fin, which
      creates propulsive jets with time-variant circulations and jet angles.
      Erectable/foldable fins provide a new design space for bioinspired underwater
      robots with structures that morph to adapt to different locomotor behaviors. This
      biorobotic fish model is also a potentially promising system for studying the
      dynamics of complex multifin fish swimming behaviors, including linear
      acceleration, steady swimming, and burst and coast, which are difficult to
      analyze in freely swimming fishes.

PMID- 29634445
TI  - The Prevention of Lower Urinary Tract Symptoms (PLUS) Research Consortium: A
      Transdisciplinary Approach Toward Promoting Bladder Health and Preventing Lower
      Urinary Tract Symptoms in Women Across the Life Course.
AB  - Lower urinary tract symptoms (LUTS) are highly prevalent in women, and are
      expected to impose a growing burden to individuals and society as the population
      ages. The predominance of research related to LUTS has focused on underlying
      pathology, disease mechanisms, or the efficacy of treatments for women with LUTS.
      Although this research has been vital for helping to reduce or ameliorate LUTS
      conditions, it has done little to prevent the onset of LUTS. Health promotion and
      prevention require an expansion of scientific inquiry beyond the traditional
      paradigm of studying disease mechanisms and treatment to the creation of an
      evidence base to support recommendations for bladder health promotion and, in
      turn, prevention of LUTS. The National Institute of Diabetes and Digestive and
      Kidney Diseases (NIDDK) introduced the concept of prevention as an important
      priority for women's urologic research as a prelude to supporting the formation
      of the Prevention of Lower Urinary Tract Symptoms (PLUS) research consortium. In
      this article, we introduce the PLUS research consortium to the scientific
      community; share the innovative paradigms by which the consortium operates; and
      describe its unique research mission: to identify factors that promote bladder
      health across the life course and prevent the onset of LUTS in girls and women.

PMID- 29634446
TI  - The National Network of State Perinatal Quality Collaboratives: A Growing
      Movement to Improve Maternal and Infant Health.
AB  - State Perinatal Quality Collaboratives (PQCs) are networks of multidisciplinary
      teams working to improve maternal and infant health outcomes. To address the
      shared needs across state PQCs and enable collaboration, Centers for Disease
      Control and Prevention (CDC), in partnership with March of Dimes and perinatal
      quality improvement experts from across the country, supported the development
      and launch of the National Network of Perinatal Quality Collaboratives (NNPQC).
      This process included assessing the status of PQCs in this country and
      identifying the needs and resources that would be most useful to support PQC
      development. National representatives from 48 states gathered for the first
      meeting of the NNPQC to share best practices for making measurable improvements
      in maternal and infant health. The number of state PQCs has grown considerably
      over the past decade, with an active PQC or a PQC in development in almost every
      state. However, PQCs have some common challenges that need to be addressed. After
      its successful launch, the NNPQC is positioned to ensure that every state PQC has
      access to key tools and resources that build capacity to actively improve
      maternal and infant health outcomes and healthcare quality.

PMID- 29634447
TI  - Insomnia But Not Hypnotics Use Associates with the Risk of Breast Cancer: A
      Population-Based Matched Cohort Study.
AB  - OBJECTIVE: The impact of hypnotic use on the association between insomnia and
      breast cancer risk remains unclear. This study examined whether insomnia
      increases the aforementioned risk and explored the effects of hypnotic use on
      this relationship. MATERIALS AND METHODS: This retrospective cohort study was
      conducted using data retrieved from the Longitudinal Health Insurance Research
      Database 2010. In total, 11,021 patients with insomnia, who were categorized by
      hypnotic use and nonuse, were identified; 22,042 age-matched participants without
      insomnia were then randomly selected. Cox proportional hazards regression was
      used for the analyses. RESULTS: The insomnia cohort had a higher risk of breast
      cancer than did the control cohort (adjusted hazard ratio [aHR] = 1.43; 95%
      confidence interval [CI] = 1.10-1.84). The aHR was 1.09 for insomniac with
      hypnotics use, 1.41 for insomniac without hypnotics use, and 0.71 for hypnotics
      users without insomnia (95% CIs = 0.71-1.68, 1.07-1.85, and 0.40-1.27) compared
      with those individuals without insomnia who did not use hypnotics. CONCLUSION:
      This nationwide population-based cohort study reveals that insomnia but not
      hypnotic use is associated with an increased risk of breast cancer.

PMID- 29634448
TI  - Deferred Personal Life Decisions of Women Physicians.
AB  - OBJECTIVE: Inadequate work-life balance can have significant implications
      regarding individual performance, retention, and on the future of the workforce
      in medicine. The purpose of this study was to determine whether women physicians
      defer personal life decisions in pursuit of their medical career. MATERIALS AND
      METHODS: We conducted a survey study of women physicians ages 20-80 from various
      medical specialties using a combination of social media platforms and women
      physicians' professional listservs with 801 survey responses collected from May
      through November 2015. The primary endpoint was whether women physicians deferred
      personal life decisions in pursuit of their medical career. Secondary outcomes
      include types of decisions deferred and correlations with age, hours worked per
      week, specialty, number of children, and career satisfaction. RESULTS:
      Respondents were categorized into deferred and nondeferred groups. Personal
      decision deferments were reported by 64% of respondents. Of these, 86% reported
      waiting to have children and 22% reported waiting to get married. Finally, while
      85% of women in the nondeferment group would choose medicine again as a career,
      only 71% of women in the deferment group would do so (p < 0.0001). Physicians who
      would choose medicine again cited reasons such as career satisfaction, positive
      patient interactions, and intellectual stimulation, whereas those who would not
      choose medicine again reported poor work-life balance, decreasing job
      satisfaction, and insurance/administrative burden. CONCLUSIONS: The results of
      this survey have significant implications on the future of the workforce in
      medicine. Overall, our analysis shows that 64% of women physicians defer
      important life decisions in pursuit of their medical career. With an increase in
      the number of women physicians entering the workforce, lack of support and
      deferred personal decisions have a potential negative impact on individual
      performance and retention. Employers must consider the economic impact and
      potential workforce shortages that may develop if these issues are not addressed.

PMID- 29634449
TI  - Screening for Childhood Adversities in Prenatal Care: What Works and Why.

PMID- 29634450
TI  - Hormonal Contraceptive Use Among Women of Older Reproductive Age: Considering
      Risks and Benefits.
AB  - As women approach menopause, fertility declines but pregnancy can still occur.
      Maternal and infant risks are increased among women of older reproductive age
      compared with younger women. A high proportion of pregnancies among women of
      older reproductive age are unintended and these pregnancies can also be
      associated with negative maternal and infant consequences. However, women and
      their healthcare providers may have concerns about risks associated with
      contraceptive use, particularly combined hormonal contraceptives, among women of
      older reproductive age who already may be at increased risk for conditions such
      as cardiovascular disease and breast cancer. Nonetheless, available evidence does
      not suggest that hormonal contraceptive use among women of older reproductive age
      substantially increases age-related risks of cardiovascular events or breast
      cancer. CDC recommends that contraception is still needed for women older than 44
      years who have not reached menopause and wish to avoid pregnancy, and that based
      on age alone, all contraceptive methods are considered safe or generally safe for
      use by women of older reproductive age.

PMID- 29634451
TI  - Ten-Year Trend in Women's Reasons for Abstaining or Limiting Drinking: The 2000
      and 2010 United States National Alcohol Surveys.
AB  - BACKGROUND: Data on individual and cultural factors contributing to drinking can
      inform screening and brief intervention in clinical practice. Our aims were to
      examine 10-year trends in women's reasons for abstaining/limiting drinking and to
      document changes in associations with drinking status for population subgroups
      defined by race/ethnicity and age. MATERIALS AND METHODS: Using repeated cross
      sectional data from White, Black and Hispanic women in the 2000 and 2010 United
      States National Alcohol Surveys (combined N = 5501), population-weighted multiple
      linear and multinomial logistic regression models assessed changes in three
      reasons for abstaining or limiting drinking (health concerns, religious
      prohibition, and upsetting family or friends) and drinking status (past-year
      abstainer, low-risk drinker, or at-risk drinker), and their associations over
      time. RESULTS: Adjusting for key demographics, reasons for limiting alcohol
      consumption declined in importance over time, with reductions in both health
      concerns and religious prohibition particularly noteworthy for older women of all
      three racial/ethnic backgrounds. Despite these reductions in importance, both
      health concerns and religious prohibition were most consistently associated with
      increased abstinence relative to low-risk drinking; these reasons were not
      strongly associated with at-risk drinking, however. CONCLUSIONS: It is essential
      for healthcare providers and others to disseminate accurate information about the
      risks of drinking to counter cultural shifts that suggest greater acceptance of
      moderate-to-heavy drinking by women aged 40 and older.

PMID- 29634452
TI  - Is the Electronic Health Record the Answer to Improving Patient Compliance with
      Recommended Health Interventions?

PMID- 29634454
TI  - Reducing contingent self-worth: A defensive response to self-threats.
AB  - Previous research shows that people with high self-esteem cope with threats to
      the self by reducing the extent to which their self-worth is contingent on the
      threatened domain (Buckingham, Weber, & Sypher, 2012). The present studies tested
      the hypothesis that this is a defensive process. In support of this hypothesis,
      Study 1 (N = 160), showed that self-affirmation attenuates the tendency for
      people with high self-esteem to reduce their contingencies of self-worth
      following self-threat. Furthermore, Study 2 (N = 286), showed that this tendency
      was more prevalent among people with defensive self-esteem than among those with
      secure self-esteem. The present studies imply that reducing contingent self-worth
      after self-threat is a defensive process. We discuss implications for theories of
      contingent self-worth.

PMID- 29634453
TI  - Sex Differences in the Relationship Between Left Ventricular Diastolic
      Dysfunction and Coronary Artery Disease: From the Korean Women's Chest Pain
      Registry.
AB  - BACKGROUND: Although coronary artery disease (CAD) is an important comorbidity,
      the influence of CAD on left ventricular diastolic dysfunction (LVDD) is not
      clear. This study aims to assess differences in the relationship between CAD and
      LVDD according to sex and comorbidities. MATERIALS AND METHODS: A total of 1109
      consecutive patients who visited an outpatient clinic with chest pain were
      included. The outcomes in 295 men and 295 women were compared after propensity
      score 1:1 matching. The evaluation of LVDD was based on guidelines recommended by
      the American Society of Echocardiography. The presence and severity of
      obstructive CAD was assessed by coronary angiography. RESULTS: After propensity
      score matching, both men and women were well balanced, with no significant
      differences of baseline covariates. Differences in diastolic functional
      parameters according to CAD severity were observed only in women (three
      parameters of LVDD except e' velocity, p < 0.05). Multiple logistic regression
      for matched pair data demonstrated that CAD severity was associated with the
      presence of LVDD only in women (odds ratio 1.919, 95% confidence interval 1.343
      2.741, p < 0.001). Interaction between sex and severity of CAD was significant (p
      = 0.025). CONCLUSIONS: The association of LVDD and CAD severity was observed only
      in women. Myocardial ischemia may be a potential pathophysiology for higher
      prevalence of LVDD and heart failure with preserved ejection fraction in women.

PMID- 29634456
TI  - iPads/tablets and students with autism: A meta-analysis of academic effects.
AB  - Since the introduction of iPads in 2010, educators have been working to
      effectively incorporate this technology as a supplement to curriculum and a tool
      to increase student engagement and student achievement. The current investigation
      examines the effectiveness of iPad applications in supporting the instruction of
      students identified on the autism spectrum. Specifically, this investigation
      provides a meta-analysis of available research that examines the use of iPad
      technology and its impact on learning outcomes for students with autism. Four
      studies were found that provided results for groups of students. The findings of
      this research are based on 12 effect-size measures, representing a synthesized
      sample size of 99 participants. The results suggest that the use of iPad
      technology can have a positive, significant effect on student learning outcomes.
      The moderators of these positive outcomes are presented and discussed.

PMID- 29634455
TI  - A series of unfortunate events: implications of Republican efforts to repeal and
      replace the Affordable Care Act For older adults.
AB  - This paper discusses Republican efforts to repeal the 2010 Patient Protection and
      Affordable Care Act (ACA) over President Trump's first year in office (2017) and
      their impact on near-elderly Americans (50-64 years old). We describe how the
      ACA's provisions for strengthening health care coverage were particularly
      advantageous for near-elderly Americans: The law shored up employer-sponsored
      health care, expanded Medicaid, and-most important-created conditions for a
      strong individual health insurance market. We then describe Republican efforts to
      undermine the ACA in the years immediately following its passage, followed by
      detailed discussion of Republican proposals to repeal and replace the ACA during
      2017. We conclude by discussing factors informing the fate of Republican
      legislation in this area, the potential consequences of the legislation that
      ultimately passed, and the prospects for future attempts to repeal and replace
      the ACA through the legislative process.

PMID- 29634457
TI  - The housing challenges of low-income older adults and the role of federal policy.
AB  - Adequate housing is critical for low-income older adults, who face affordability
      and accessibility challenges that affect their quality of life, health, and
      ability to live independently in their communities. This article examines the
      federal policy role in meeting the housing and housing-related needs of the low
      income elderly population, which is expected to grow as a proportion of all older
      adults over the next two decades. The availability of publicly subsidized units
      and vouchers is woefully inadequate to assist the current low-income elderly
      population in need of rental assistance. While access to affordable and
      accessible housing options has been a growing challenge for several decades, the
      Trump administration and Republican-majority Congress has an agenda and specific
      budgetary, administrative, and legislative proposals that would worsen the
      housing situation today and into the future. Population aging combined with a
      lack of investment in affordable senior housing and related programs over the
      last two decades requires a call to action for stakeholders in the public and
      private sectors to jointly develop a comprehensive national senior housing policy
      agenda and implementation strategy.

PMID- 29634458
TI  - Pornography Consumption, Perceptions of Pornography as Sexual Information, and
      Condom Use.
AB  - Pornography use is becoming more commonplace and may be a modality by which
      individuals receive sex education. This survey study assessed pornography
      consumption, perceptions of pornography as a source of sexual information, and
      condom use in a heterosexual sample of 200 sexually active German adults who were
      not in monogamous relationships. At the bivariate, overall sample level, there
      was only a modest association between consuming pornography and a decreased
      frequency of condom use. However, consistent with the sexual script acquisition,
      activation, application model (3AM) of sexual media socialization, this
      association was moderated by differential perceptions of pornography as a source
      of sexual information. Interaction decomposition revealed that there was no
      association between pornography consumption and condom use among participants who
      disagreed that pornography is a source of sexual information. Conversely,
      pornography consumption was associated with a lower frequency of condom use among
      participants who agreed that pornography is a source of sexual information. As
      the perception that pornography is a source of sexual information strengthened,
      the relationship between pornography consumption and less frequent condom use
      increased. Gender did not moderate these associations. These findings point
      toward the importance of fostering a critical reading of pornography through
      media literacy education.

PMID- 29634459
TI  - Reducing Risk: Counseling Men Infected with HIV Who Have Sex with Men on Safer
      Sex Practices with Seroconcordant Partners.
AB  - The incidence of new HIV infections in the United States continues to be greatest
      among men who have sex with men (MSM). MSM infected with HIV often seek
      seroconcordant sexual partners based on intent to limit psychosocial, legal, and
      health risks they perceive as higher with serodiscordant sexual partners.
      However, the rationales for limiting sexual relationships exclusively with other
      MSM infected with HIV may be rooted in misinformation or misperception. Thus,
      these clients may have a unique sexual health knowledge deficit that nurses,
      social workers, and other clinicians need to address to help them reduce risk.
      This article focuses on sexually related health risks that are distinct to MSM
      infected with HIV seroconcordant partners. Data on the most recent HIV-infection
      incidence rates in MSM in the United States is provided. Discussion concentrates
      on the risk these individuals may have in communicating and acquiring sexually
      transmitted diseases other than HIV, the risk of HIV superinfection, and how
      sexually transmitted diseases affect persons who are immunocompromised
      differently than those who are immunocompetent. Finally, recommendations for
      healthcare professionals who counsel MSM infected with HIV in sexual decision
      making is provided.

PMID- 29634461
TI  - From the Editor.

PMID- 29634460
TI  - Analysis of the Uptake, Metabolism, and Behavioral Effects of Cannabinoids on
      Zebrafish Larvae.
AB  - The Cannabis sativa plant contains numerous phytocannabinoids and terpenes with
      known or potential biological activity. For decades, plant breeders have been
      breeding the Cannabis plant to control for a desired ratio of the major
      cannabinoids. A high-throughput in vivo model to understand the relationship
      between the chemical composition of different strains and their therapeutic
      potential then becomes of value. Measuring changes in the behavioral patterns of
      zebrafish larvae is an established model with which to test the biological
      activity of neuroactive compounds. However, there is currently little information
      regarding the uptake kinetics and metabolism of compounds by larvae. In this
      study, we chose to compare the uptake kinetics and metabolism of Delta9
      tetrahydrocannabinol (THC) and cannabidiol (CBD) alone or in combination with
      their effects on larval behavior. We have shown that both compounds have distinct
      behavioral patterns and concentration response profiles. Additionally, the uptake
      kinetics observed for each compound appears to correlate with the change in
      behavior observed in the behavioral assays. When combinations of THC and CBD were
      tested there were shifts in both the behavioral activity and the uptake kinetics
      of each compound compared with when they were tested alone. Finally, the THC/CBD
      derived metabolites detected in the larvae are similar to those found in
      mammalian systems. This study thus provides a model for further testing of
      additional cannabinoids and potentially plant extracts.

PMID- 29634462
TI  - Understanding the tests we order: Comments and an invitation.

PMID- 29634463
TI  - Musculoskeletal ultrasonography has arrived.

PMID- 29634464
TI  - Make no bones about it!

PMID- 29634465
TI  - Are serum troponin levels elevated in conditions other than acute coronary
      syndrome?

PMID- 29634466
TI  - Musculoskeletal ultrasonography basics.
AB  - Utrasonography is emerging as a core method to evaluate musculoskeletal problems.
      It is best used for imaging superficial structures limited to 1 quadrant of a
      joint. It has several advantages over other imaging methods: lower cost, ability
      to perform dynamic examinations, higher spatial resolution of superficial
      structures, better patient comfort, and essentially no contraindications.

PMID- 29634467
TI  - The female athlete triad: It takes a team.
AB  - The female athlete triad is a syndrome consisting of low energy availability (ie,
      burning more calories than one is taking in), menstrual dysfunction, and low bone
      mineral density, although all 3 components need not be present. Many providers,
      physical therapists, and coaches are unaware of it and thus do not screen for it.
      Early intervention using a team approach is essential in patients with any
      component of the female athlete triad to prevent long-term adverse health
      effects.

PMID- 29634468
TI  - Gallstones: Watch and wait, or intervene?
AB  - Gallstones are common in the United States, affecting an estimated 1 in 7 adults.
      Fortunately, they are asymptomatic in up to 80% of cases, and current guidelines
      do not recommend cholecystectomy unless they cause symptoms. Laparoscopic
      cholecystectomy is the standard treatment for symptomatic gallstones, acute
      cholecystitis, and gallstone pancreatitis.

PMID- 29634469
TI  - A 71-year-old woman with shock and a high INR.

PMID- 29634470
TI  - Hyperkeratotic fissured plaques on both hands: Mechanic's hands.

PMID- 29634471
TI  - Hidden lesion easily missed on chest radiography.

PMID- 29634472
TI  - To the Editor: Perioperative interruption of dual antiplatelet therapy.

PMID- 29634473
TI  - In reply: Perioperative interruption of dual antiplatelet therapy.

PMID- 29634474
TI  - Correction: Gas under the right diagphragm.
AB  - In the article, "Gas under the right diaphragm" (Matsuura H, Hata H. Cleve Clin J
      Med 2018; 85[2]:98-100), Figure 2 appeared upside down. It should have appeared
      as shown on the online version at www.ccjm.org.

PMID- 29634475
TI  - Correction: Physical examination in dyspnea.
AB  - On page 949 of the article, "Diagnostic value of the physical examination in
      patients with dyspnea" (Shellenberger RA, Balakrishnan B, Avula S, Ebel A, Shaik
      S. Cleve Clin J Med 2017; 84[12]:943-950), the terms "abdominojugular reflex" and
      "hepatojugular reflex" should have been "abdominojugular reflux" and
      "hepatojugular reflux." This error also occurred in Table 5 on that page.

PMID- 29634477
TI  - A simple transformation independent method for outlier definition.
AB  - BACKGROUND: Definition and elimination of outliers is a key element for medical
      laboratories establishing or verifying reference intervals (RIs). Especially as
      inclusion of just a few outlying observations may seriously affect the
      determination of the reference limits. Many methods have been developed for
      definition of outliers. Several of these methods are developed for the normal
      distribution and often data require transformation before outlier elimination.
      METHODS: We have developed a non-parametric transformation independent outlier
      definition. The new method relies on drawing reproducible histograms. This is
      done by using defined bin sizes above and below the median. The method is
      compared to the method recommended by CLSI/IFCC, which uses Box-Cox
      transformation (BCT) and Tukey's fences for outlier definition. The comparison is
      done on eight simulated distributions and an indirect clinical datasets. RESULTS:
      The comparison on simulated distributions shows that without outliers added the
      recommended method in general defines fewer outliers. However, when outliers are
      added on one side the proposed method often produces better results. With
      outliers on both sides the methods are equally good. Furthermore, it is found
      that the presence of outliers affects the BCT, and subsequently affects the
      determined limits of current recommended methods. This is especially seen in
      skewed distributions. The proposed outlier definition reproduced current RI
      limits on clinical data containing outliers. CONCLUSIONS: We find our simple
      transformation independent outlier detection method as good as or better than the
      currently recommended methods.

PMID- 29634476
TI  - Abnormal dynamic functional connectivity of amygdalar subregions in untreated
      patients with first-episode major depressive disorder.
AB  - BACKGROUND: Accumulating evidence supports the concept of the amygdala as a
      complex of structurally and functionally heterogeneous nuclei rather than as a
      single homogeneous structure. However, changes in resting-state functional
      connectivity in amygdalar subregions have not been investigated in major
      depressive disorder (MDD). Here, we explored whether amygdalar subregions -
      including the laterobasal, centromedial (CM) and superficial (SF) areas -
      exhibited distinct disruption patterns for different dynamic functional
      connectivity (dFC) properties, and whether these different properties were
      correlated with clinical information in patients with MDD. METHODS: Thirty
      untreated patients with first-episode MDD and 62 matched controls were included.
      We assessed between-group differences in the mean strength of dFC in each
      amygdalar subregion in the whole brain using general linear model analysis.
      RESULTS: The patients with MDD showed decreased strength in positive dFC between
      the left CM/SF and brainstem and between the left SF and left thalamus; they
      showed decreased strength in negative dFC between the left CM and right superior
      frontal gyrus (p < 0.05, family-wise error-corrected). We found significant
      positive correlations between age at onset and the mean positive strength of dFC
      in the left CM/brainstem in patients with MDD. LIMITATIONS: The definitions of
      amygdalar subregions were based on a cytoarchitectonic delineation, and the
      temporal resolution of the fMRI was slow (repetition time = 2 s). CONCLUSION:
      These findings confirm the distinct dynamic functional pathway of amygdalar
      subregions in MDD and suggest that the limbic-cortical-striato-pallido-thalamic
      circuitry plays a crucial role in the early stages of MDD.

PMID- 29634478
TI  - International Consensus on Antinuclear Antibody Patterns: defining negative
      results and reporting unidentified patterns.

PMID- 29634479
TI  - Improving the attitudes of primary care practitioners toward adolescent care: a
      pre-post intervention pilot study.
AB  - Background Investing in adolescent health is among the most cost-effective health
      measures. Primary care practitioners are ideally positioned to deliver such
      interventions. However, several barriers hinder them from engaging with
      adolescents. Objective To pilot test the impact of a 1-day training session on
      adolescent health on the attitudes of primary care practitioners toward
      adolescent care. Subjects Participants were family physicians and nurses enrolled
      in a 1-day training session on adolescent health. Methods A non-randomized, pre
      post intervention study with no control group. Data on barriers for providing
      care to adolescents, preferred pediatric age group and attitudes toward
      adolescent care were collected immediately prior. Participants' attitudes were
      measured again immediately after training. Results Most participants reported
      they preferred to attend pediatric groups other than adolescents. The most
      frequently reported barriers were: excessive amount of time needed and lack of
      training. Participants reported positive pre-training attitudes, with mean scores
      above the midpoint of the scale in all dimensions. Significant positive
      improvements were observed after training in Adequacy, Self-esteem and
      Satisfaction. Subgroup analysis showed that at baseline, professionals who
      preferred to work with adolescents had significantly more positive attitudes in
      Adequacy, Self-esteem and Satisfaction. After training there was a general
      improvement in attitudes in both groups, with attenuation of the differences
      between them. Conclusion Participation in a 1-day tailored educational
      intervention on adolescent health had a positive impact on the attitudes of
      primary care practitioners, regardless of their preferred age group. This
      improvement may lead to more active engagement with adolescents and substantial
      health gains.

PMID- 29634480
TI  - Environmental perceptions and its associations with physical fitness and body
      composition in adolescents: longitudinal results from the LabMed Physical
      Activity Study.
AB  - Background The environmental correlates have been extensively studied in the last
      years, but most associations with physical fitness (PF) and body composition have
      been cross-sectional in nature. Objective This study aimed to determine if
      adolescents' environmental perceptions associated with PF and body composition in
      a 2-year follow-up. Subjects Participants were 583 adolescents aged 12-18 years
      (299 girls) from the LabMed Physical Activity Study. Methods PF and body
      composition were assessed with the protocols of the ALPHA health-related fitness
      battery and environmental perceptions with the ALPHA environmental questionnaire.
      Linear regression models were used to determine the associations between
      environmental perceptions at baseline and PF and anthropometric measures at
      follow-up. Results Results showed that perceptions of distant facilities at
      baseline were associated with lower fitness at follow-up in boys. Also, boys'
      lower study environment perceptions at baseline were associated with higher body
      composition at follow-up. Positive perceptions of a pleasant environment at
      baseline were associated with better fitness at follow-up in boys. Additionally,
      girls' positive bike lanes availability and esthetics perceptions at baseline
      were associated with better body composition at follow-up. Conclusion Positive
      environmental perceptions at baseline are associated with better PF and body
      composition at follow-up.

PMID- 29634482
TI  - Influence of Loranthus micranthus on hepatic and renal antioxidant status and
      impaired glycolytic flux in streptozotocin-induced diabetic rats.

PMID- 29634481
TI  - Effects of acetone extract of Cola nitida on brain sodium-potassium adenosine
      triphosphatase activity and spatial memory in healthy and streptozotocin-induced
      diabetic female Wistar rats.
AB  - Background This study was carried out to investigate the effects of acetone
      extract of Cola nitida on brain Na+/K+-ATPase activity and spatial memory of
      healthy and streptozotocin (STZ)-induced diabetic female Wistar rats. Methods
      Forty-two female Wistar rats were used for this study and were randomly
      distributed into six groups (n=7). Rats in group 1 were used as control and were
      administered normal saline; group 2 rats were healthy rats administered 50 mg/kg
      of kola nut extract per day; group 3 rats were healthy rats administered 100
      mg/kg of kola nut extract per day; group 4 rats were a diabetic group also
      administered normal saline; group 5 rats were diabetic rats administered 50 mg/kg
      of kola nut extract per day; and group 6 rats were diabetic rats administered 100
      mg/kg of kola nut extract per day. Diabetes was induced with 50 mg/kg of STZ.
      After 3 weeks of administration, the spatial memories of the rats were tested
      using the Y-maze, followed by assay of Na+/K+-ATPase activity. Results The result
      shows a significant increase in Na+/K+-ATPase activity of diabetic treated groups
      (5 and 6) when compared with the diabetic group (4) and a significant increase in
      Na+/K+-ATPase activity of healthy treated groups (2 and 3) when compared with
      control. Also, there was a significant increase in spatial memory of the diabetic
      treated groups when compared with diabetic group. Conclusions This study revealed
      that kola nut extract has restorative effect on brain Na+/K+-ATPase activities
      and spatial memory of STZ-induced diabetic female Wistar rats.

PMID- 29634483
TI  - Anti-inflammatory and insulin secretory activity in experimental type-2 diabetic
      rats treated orally with magnesium.

PMID- 29634484
TI  - Haloperidol-induced parkinsonism is attenuated by varenicline in mice.
AB  - Background Parkinson's disease (PD) is a neurodegenerative disorder of the
      central nervous system (CNS). However, there is no known drug to stop/slow down
      this neurodegeneration. Varenicline is an anti-smoking drug and has the potential
      to prevent neurodegeneration. Thus, the present study was designed to evaluate
      the effect of varenicline in animal models of PD. Methods Levodopa and
      haloperidol were administered in doses of 30 and 1 mg/kg, intraperitoneally
      (i.p.), respectively. Group 1 was administered haloperidol; groups 2, 3 and 4
      were administered haloperidol along with varenicline in doses of 0.5, 1.5 and 2.5
      mg/kg, i.p., respectively and group 5 was administered levodopa along with
      haloperidol. Varenicline was administered daily, 30 min prior to the
      administration of haloperidol. Varenicline was administered for the first 8 days,
      and then from the 9th day until the 15th day. Behavioral assessment (rotarod and
      catalepsy tests) was performed on days 9 and 15. Assessment of striatal dopamine
      levels and histopathology were also performed. Results In the haloperidol-treated
      groups, significant decrease in latency to fall off (on rotarod) and increase in
      catalepsy duration (in catalepsy test) were observed as compared to the control
      group. In the levodopa-treated group, significant increase in latency to fall off
      the rotarod and significant decrease in catalepsy duration were observed as
      compared to the haloperidol-treated groups. Further, on day 9, varenicline (2.5
      mg/kg) significantly increased the latency to fall off the rotarod, while
      varenicline (0.5 and 1.5 mg/kg) did not cause any significant change in latency
      to fall off the rotarod as compared to the haloperidol-treated group. On day 15,
      significant increase in latency to fall off the rotarod was observed in
      varenicline (at all doses) as compared to the haloperidol-treated group. In the
      catalepsy test, the varenicline-treated (at all doses) groups showed significant
      decrease in duration of catalepsy on day 9 and day 15 as compared to the
      haloperidol-treated group. Significant decrease in striatal dopamine levels was
      observed among the haloperidol-treated groups as compared to the control group.
      Further, varenicline-treated (at all doses) and levodopa-treated groups showed
      significant increase in striatal dopamine levels when compared with the
      haloperidol-treated group. In histology, varenicline (0.5 mg/kg) showed moderate
      decrease in neurons, while varenicline (1.5 and 2.5 mg/kg) showed mild decrease
      in neurons. However, the levodopa-treated group did not show any significant
      decrease in neurons. Thus, varenicline has shown promising results and has
      provided novel strategy for the treatment of PD.

PMID- 29634485
TI  - Autonomic responses during acute myocardial infarction in the rat model:
      implications for arrhythmogenesis.
AB  - Background Autonomic responses participate in the pathophysiology of acute
      myocardial infarction, but their precise time course remains unclear. Here, we
      investigated the autonomic activity and ventricular tachyarrhythmias in
      conscious, unrestrained rats post-infarction. Methods The left coronary artery
      was ligated in 12 Wistar rats, and six rats were sham operated, followed by 24-h
      electrocardiographic recording via implanted telemetry transmitters. Sympathetic
      activity was assessed by detrended fluctuation analysis and vagal activity by
      time- and frequency-domain analysis of heart rate variability. The duration of
      the ventricular tachyarrhythmias was measured, and voluntary motion served as a
      marker of heart failure. Results In sham-operated rats, heart rate and
      sympathetic activity remained low, whereas vagal activity rose progressively
      after the fourth hour. Post-ligation, medium-sized antero-septal necrosis was
      observed, reaching ~20% of the left ventricular volume; tachyarrhythmias were
      frequent, displaying a bimodal curve, and motion counts were low. Vagal activity
      decreased early post-ligation, coinciding with a high incidence of
      tachyarrhythmias, but tended to rise subsequently in rats with higher motion
      counts. Sympathetic activity increased after the third hour, along with a second
      tachyarrhythmia peak, and remained elevated throughout the 24-h period.
      Conclusions Vagal withdrawal, followed by gradual sympathetic activation, may
      participate in arrhythmogenesis during acute myocardial infarction.

PMID- 29634486
TI  - Anti-plasmodial activity of sodium acetate in Plasmodium berghei-infected mice.

PMID- 29634488
TI  - Characterization of the exradin W1 plastic scintillation detector for small field
      applications in proton therapy.
AB  - Accurate dosimetry in small field proton therapy is challenging, particularly for
      applications such as ocular therapy, and suitable detectors for this purpose are
      sought. The Exradin W1 plastic scintillating fibre detector is known to out
      perform most other detectors for determining relative dose factors for small
      megavoltage photon beams used in radiotherapy but its potential in small proton
      beams has been relatively unexplored in the literature. The 1 mm diameter
      cylindrical geometry and near water equivalence of the W1 makes it an attractive
      alternative to other detectors. This study examines the dosimetric performance of
      the W1 in a 74 MeV proton therapy beam with particular focus on detector response
      characteristics relevant to relative dose measurement in small fields suitable
      for ocular therapy. Quenching of the scintillation signal is characterized and
      demonstrated not to impede relative dose measurements at a fixed depth. The
      background cable-only (Cerenkov and radio-fluorescence) signal is 4 orders of
      magnitude less than the scintillation signal, greatly simplifying relative dose
      measurements. Comparison with other detectors and Monte Carlo simulations
      indicate that the W1 is useful for measuring relative dose factors for field
      sizes down to 5 mm diameter and shallow spread out Bragg peaks down to 6 mm in
      depth.

PMID- 29634487
TI  - Association between UCP polymorphisms and adipokines with obesity in Mexican
      adolescents.
AB  - BACKGROUND: It has been reported that the uncoupling proteins (UCPs) can
      contribute to energy metabolism, and are thus involved in the pathogenesis of
      obesity. The objective of the study was to analyze the association between UCP
      polymorphisms, clinical parameters and leptin and adiponectin plasma levels in an
      adolescent population with overweight and obesity. METHODS: We analyzed the UCP1 
      3826 C/T, UCP2-866 G/A, Ala55Val and UCP3 -55 C/T polymorphisms and the levels of
      adipokines in adolescents with normal weight and with overweight or obesity. The
      study included 270 students aged between 12 and 18 years categorized according to
      the percentiles from Mexico City. Adipokines levels were measured by immunoassay
      methods and the UCP polymorphisms were determined using Taqman real-time
      polymerase chain reaction (RT-PCR). RESULTS: No significant differences were
      found in the UCP polymorphisms in seven inheritance models studied. Most of the
      significant differences in the clinical parameters were found under a recessive
      model, the UCP2 -866 polymorphism was associated with diastolic blood pressure
      (p=0.008), triglycerides (p=0.045), low-density lipoprotein-cholesterol (LDL-C)
      (p=0.003), high-density lipoprotein-cholesterol (HDL-C) (p=0.050) and plasma
      levels of leptin (p<0.001). Also, the obese group was found to have higher leptin
      levels and lower adiponectin levels in GA+AA vs. GG (recessive model).
      CONCLUSIONS: This study demonstrated a direct relationship between the clinical
      characteristics and UCP2-866 in a recessive model, associated with high levels of
      leptin and decreased levels of adiponectin in an obese or overweight Mexican
      adolescent population.

PMID- 29634491
TI  - Comparison of Anterior Suprascapular, Supraclavicular, and Interscalene Nerve
      Block Approaches for Major Outpatient Arthroscopic Shoulder Surgery: A
      Randomized, Double-blind, Noninferiority Trial.
AB  - BACKGROUND: The interscalene nerve block provides analgesia for shoulder surgery,
      but is associated with diaphragm paralysis. One solution may be performing
      brachial plexus blocks more distally. This noninferiority study evaluated
      analgesia for blocks at the supraclavicular and anterior suprascapular levels,
      comparing them individually to the interscalene approach. METHODS: One hundred
      eighty-nine subjects undergoing arthroscopic shoulder surgery were recruited to
      this double-blind trial and randomized to interscalene, supraclavicular, or
      anterior suprascapular block using 15 ml, 0.5% ropivacaine. The primary outcome
      was numeric rating scale pain scores analyzed using noninferiority testing. The
      predefined noninferiority margin was one point on the 11-point pain scale.
      Secondary outcomes included opioid consumption and pulmonary assessments.
      RESULTS: All subjects completed the study through the primary outcome analysis.
      Mean pain after surgery was: interscalene = 1.9 (95% CI, 1.3 to 2.5),
      supraclavicular = 2.3 (1.7 to 2.9), suprascapular = 2.0 (1.4 to 2.6). The primary
      outcome, mean pain score difference of supraclavicular-interscalene was 0.4 (-0.4
      to 1.2; P = 0.088 for noninferiority) and of suprascapular-interscalene was 0.1 (
      0.7 to 0.9; P = 0.012 for noninferiority). Secondary outcomes showed similar
      opioid consumption with better preservation of vital capacity in the anterior
      suprascapular group (90% baseline [P < 0.001]) and the supraclavicular group (76%
      [P = 0.002]) when compared to the interscalene group (67%). CONCLUSIONS: The
      anterior suprascapular block, but not the supraclavicular, provides noninferior
      analgesia compared to the interscalene approach for major arthroscopic shoulder
      surgery. Pulmonary function is best preserved with the anterior suprascapular
      nerve block.

PMID- 29634489
TI  - CNS myeloid cells critically regulate heat hyperalgesia.
AB  - Activation of non-neuronal microglia is thought to play a causal role in spinal
      processing of neuropathic pain. To specifically investigate microglia-mediated
      effects in a model of neuropathic pain and overcome the methodological
      limitations of previous approaches exploring microglia function upon nerve
      injury, we selectively ablated resident microglia by intracerebroventricular
      ganciclovir infusion into male CD11b-HSVTK-transgenic mice, which was followed by
      a rapid, complete, and persistent (23 weeks) repopulation of the CNS by
      peripheral myeloid cells. In repopulated mice that underwent sciatic nerve
      injury, we observed a normal response to mechanical stimuli, but an absence of
      thermal hypersensitivity ipsilateral to the injured nerve. Furthermore, we found
      that neuronal expression of calcitonin gene-related peptide (CGRP), which is a
      marker of neurons essential for heat responses, was diminished in the dorsal horn
      of the spinal cord in repopulated mice. These findings identify distinct
      mechanisms for heat and mechanical hypersensitivity and highlight a crucial
      contribution of CNS myeloid cells in the facilitation of noxious heat.

PMID- 29634490
TI  - Real-world healthcare costs of ipilimumab in patients with advanced cutaneous
      melanoma in The Netherlands.
AB  - There is limited evidence on the costs associated with ipilimumab. We
      investigated healthcare costs of all Dutch patients with advanced cutaneous
      melanoma who were treated with ipilimumab. Data were retrieved from the nation
      wide Dutch Melanoma Treatment Registry. Costs were determined by applying unit
      costs to individual patient resource use. A total of 807 patients who were
      diagnosed between July 2012 and July 2015 received ipilimumab in Dutch practice.
      The mean (median) episode duration was 6.27 (4.61) months (computed from the
      start of ipilimumab until the start of a next treatment, death, or the last date
      of follow-up). The average total healthcare costs amounted to &OV0556;81 484, but
      varied widely (range: &OV0556;18 131-&OV0556;160 002). Ipilimumab was by far the
      most important cost driver (&OV0556;73 739). Other costs were related to hospital
      admissions (&OV0556;3323), hospital visits (&OV0556;1791), diagnostics and
      imaging (&OV0556;1505), radiotherapy (&OV0556;828), and surgery (&OV0556;297).
      Monthly costs for resource use other than ipilimumab were &OV0556;1997 (SD:
      &OV0556;2629). Treatment-naive patients (n=344) had higher total costs compared
      with previously-treated patients (n=463; &OV0556;85 081 vs. &OV0556;78 811).
      Although patients with colitis (n=106) had higher costs for resource use other
      than ipilimumab (&OV0556;11 426) compared with patients with other types of
      immune-related adverse events (n=90; &OV0556;9850) and patients with no immune
      related adverse event (n=611; &OV0556;6796), they had lower total costs
      (&OV0556;76 075 vs. &OV0556;87 882 and &OV0556;81 480, respectively). In
      conclusion, this nation-wide study provides valuable insights into the healthcare
      costs of advanced cutaneous melanoma patients who were treated with ipilimumab in
      clinical practice. Most of the costs were attributable to ipilimumab, but the
      costs and its distribution varied considerably across subgroups.

PMID- 29634492
TI  - Review on Factors Influencing Physician Guideline Adherence in Cardiology.
AB  - Cardiovascular disease is the most common cause of death in Western countries.
      Physician adherence to guidelines is often suboptimal, resulting in impaired
      patient outcome and prognosis. Multiple studies have been conducted to evaluate
      patterns and the influencing factors of patient adherence, but little is known
      about factors influencing physician guideline adherence. This review aims to
      identify factors influencing physician guideline adherence relevant to cardiology
      and to provide insights and suggestions for future improvement. Physician
      adherence was measured as adherence to standard local medical practice and
      applicable guidelines. Female gender and older age had a negative effect on
      physician guideline adherence. In addition, independent of the type of heart
      disease, physicians without cardiologic specialization were linked to physician
      noncompliance. Also, guideline adherence in primary care centers was at a lower
      level compared to secondary or tertiary care centers. The importance of guideline
      adherence increases as patients age, and complex diseases and comorbidity arise.
      Appropriate resources and interventions, taking important factors for
      nonadherence in account, are necessary to improve guideline adoption and
      adherence in every level of the chain. This in turn should improve patient
      outcome.

PMID- 29634493
TI  - Metformin: old friend, new ways of action-implication of the gut microbiome?
AB  - PURPOSE OF REVIEW: Gut dysbiosis was recently associated with the occurrence of
      type 2 diabetes (T2D). In addition to this finding, an increasing number of
      studies performed upon the last 5 years have also shown that metformin treatment
      leads to changes in gut bacterial composition in diabetic patients. This review
      focuses on the articles describing the effects of metformin on gut homeostasis
      (including the gut microbiota) and proposes potential mechanisms involved in
      those effects. RECENT FINDINGS: Several human and animal studies emphasized that
      metformin alters the gut microbiota composition by enhancing the growth of some
      bacteria, such as Akkermansia muciniphila, Escherichia spp. or Lactobacillus and
      by decreasing the levels of some other ones like Intestinibacter. In-vitro
      studies also demonstrated a direct action of metformin on the growth of A.
      muciniphila and Bifidobacterium adolescentis. Moreover, in the intestines,
      metformin does not only improve the glucose uptake, but it also promotes the
      short-chain fatty acid (SCFA) production, protects the intestinal barrier and
      regulates the secretion of gut peptides SUMMARY: It is now clear that gut
      microbiota participates to the glucose-lowering effects of metformin in the
      context of diabetes. Further work is now needed to determine the exact mechanisms
      of action of the drug and to understand by which processes metformin is able to
      enhance the growth of some bacteria exhibiting beneficial effects for the host.

PMID- 29634494
TI  - Assessment of fluid responsiveness: recent advances.
AB  - PURPOSE OF REVIEW: In the field of prediction of fluid responsiveness, the most
      recent studies have focused on validating new tests, on clarifying the
      limitations of older ones, and better defining their modalities. RECENT FINDINGS:
      The limitations of pulse pressure/stroke volume variations are numerous, but
      recent efforts have been made to overcome these limitations, like in case of low
      tidal volume ventilation. Following pulse pressure/stroke volume variations, new
      tests have emerged which assess preload responsiveness by challenging cardiac
      preload through heart-lung interactions, like during recruitment manoeuvres and
      end-expiratory/inspiratory occlusions. Given the risk of fluid overload that is
      inherent to the 'classical' fluid challenge, a 'mini' fluid challenge, made of
      100 ml of fluid only, has been developed and investigated in recent studies. The
      reliability of the passive leg raising test is now well established and the
      newest publications have mainly aimed at defining several noninvasive estimates
      of cardiac output that can be monitored to assess its effects. SUMMARY: Research
      in this field is still very active, such that several indices and tests of fluid
      responsiveness are now available. They may contribute to reduce excessive fluid
      balance by avoiding unnecessary fluid administration and, also, by ensuring safe
      fluid removal.

PMID- 29634496
TI  - Recent developments in persufflation for organ preservation.
AB  - PURPOSE OF REVIEW: To summarize current literature and recent findings on the
      potential of humidified oxygenated gas perfusion (persufflation) as an
      alternative method for improved organ preservation. RECENT FINDINGS: Although
      there are some conflicting data, the majority of the evidence suggests that
      persufflation, by enhancing oxygenation, can improve preservation and even rescue
      organs, including organs with prior exposure to warm ischemia. In some cases,
      persufflation produced better results than hypothermic machine perfusion. The
      timing of persufflation is of importance; benefits of persufflation appear to
      increase as the timing of its administration postprocurement decreases. This may
      be particularly true for tissues that are more sensitive to ischemia, such as the
      pancreas prior to islet isolation. Combining oxygen persufflation with nitric
      oxide and addition of pulsatile flow may provide further benefits and amplify its
      effects on improving transplant outcomes. SUMMARY: Persufflation is a promising,
      relatively simple, preservation technique that enables improved oxygenation,
      which provides protection and improvement in the graft condition during
      preservation and prior to transplantation. More detailed studies are needed to
      optimize persufflation and evaluate its short and long-term effects in vivo.

PMID- 29634495
TI  - A behavioral economic analysis of the value-enhancing effects of nicotine and
      varenicline and the role of nicotinic acetylcholine receptors in male and female
      rats.
AB  - Reinforcement value enhancement by nicotine of non-nicotine rewards is believed
      to partially motivate smoking behavior. Recently, we showed that the value
      enhancing effects of nicotine are well characterized by reinforcer demand models
      and that the value-enhancing effects of the smoking-cessation aid bupropion
      (Zyban) are distinct from those of nicotine and differ between the sexes. The
      present study evaluated potential sex differences in the enhancement effects of
      nicotine and varenicline (Chantix) using a reinforcer demand methodology. The
      role of alpha4beta2* and alpha7 nicotinic acetylcholine receptors (nAChRs) in the
      enhancing effects of nicotine and varenicline is also evaluated. Male and female
      rats (n=12/sex) were trained to lever press maintained by sensory reinforcement
      by visual stimulus (VS) presentations. Changes in the VS value following nicotine
      and varenicline administration were assessed using an established reinforcer
      demand approach. Subsequently, the effects of antagonism of alpha4beta2* and
      alpha7 nAChRs on varenicline and nicotine-induced enhancement active lever
      pressing were assessed using a progressive ratio schedule. Nicotine and
      varenicline enhanced VS demand equivalently between the sexes as evaluated by
      reinforcer demand. However, alpha4beta2* receptor antagonism attenuated value
      enhancement by nicotine and varenicline in females, but only of nicotine in
      males.

PMID- 29634497
TI  - Psychometric Properties of the Canadian Nurse Informatics Competency Assessment
      Scale.
AB  - Assessment of nursing informatics competencies has gained momentum in the
      scholarly literature in response to the increased need for resources available to
      support informatics capacity in nursing. The purpose of this study was to examine
      the factor structure and internal consistency reliability of the Canadian Nurse
      Informatics Competency Assessment Scale, a newly developed 21-item measure based
      on published entry-to-practice informatics competencies for RNs. For this study,
      2844 nurses completed the Canadian Nurse Informatics Competency Assessment Scale
      through a cross-sectional survey. Exploratory principal component analysis with
      oblique promax rotation revealed a four-component/factor structure for the 21
      item Canadian Nurse Informatics Competency Assessment Scale, explaining 61.04% of
      the variance. Item loading per each component reflected the original Canadian
      Association of Schools of Nursing grouping of nursing informatics competency
      indicators, as per three key domains of competency: information and knowledge
      management (alpha = .85); professional and regulatory accountability (alpha =
      .81); and use of information and communication technology in the delivery of
      patient care (alpha = .87) with the exception of one item (Indicator 3), which
      loaded into the category of foundational information and communication technology
      skills (alpha = .81). This study provided preliminary evidence for the construct
      validity of the entry-to-practice competency domains and the factor structure and
      reliability of the Canadian Nurse Informatics Competency Assessment Scale among
      practicing nurses. Further testing among nurses in other settings and among
      nursing students is recommended.

PMID- 29634498
TI  - Online Clinical Post Conference: Strategies for Meaningful Discussion Using
      VoiceThread.
AB  - Clinical post conference (CPC) is a strategy for peer learning and reflective
      discourse after clinical experiences. Reflective and experiential learning
      practices are essential in nursing education to develop students' critical
      thinking. Innovative approaches to structure asynchronous online CPC using
      VoiceThread offer time for student reflection, while retaining the value of
      facial cues, tone, and peer-peer connections occurring during traditional face-to
      face CPC.

PMID- 29634499
TI  - Achieving Outcomes With Innovative Smart Pump Technology: Partnership, Planning,
      and Quality Improvement.
AB  - BACKGROUND: A 5-time designated Magnet academic medical center partnered with its
      infusion systems supplier to successfully integrate 1327 smart pumps across 45
      departments with an aggressive 3-month timeline. The team also achieved quality
      improvement (QI) outcomes through increased drug library compliance and decreased
      alerts with their new technology. PROBLEM: This large academic medical center
      needed to implement innovative wireless infusion pump technology in a short time
      frame. APPROACH: The approach involved a strong partnership from the medical
      center and the supplier, with extensive planning and collaboration among the
      clinical nurse specialists and consultants from both organizations to accomplish
      QI goals. Lean principles were also followed to enhance efficiency and
      accountability. OUTCOMES: Quality improvement outcomes included 100% drug library
      compliance across all 6 intensive care units, a decrease in pump alert rates from
      4.18% to 0.79%, and a decrease in pump programming correction rate from 0.36% to
      0.06%. CONCLUSIONS: A partnership led to a large implementation being completed
      efficiently across an academic medical center. Through these joint efforts,
      quality of care was improved within a short period of time.

PMID- 29634500
TI  - The Unexpected Life: Living With Hand Transplants.

PMID- 29634501
TI  - Comparison of Outcomes of Total Esophageal Reconstruction With Supercharged
      Jejunal Flap, Colonic Interposition, and Gastric Pull-up.
AB  - BACKGROUND: Esophageal reconstruction following esophagectomy is a complex
      operation with significant morbidity. Gastric pull-up (GPU) has historically been
      the first-line operation followed by the colonic interposition (CI) graft, but
      recently, the use of a pedicled, supercharged jejunal flap (SJF) has reemerged as
      an alternative. However, comprehensive reports on outcomes of SJFs remain
      limited, with exceedingly few direct comparisons of outcomes. METHODS: A
      retrospective chart review was completed for patients who underwent thoracic or
      total esophageal reconstruction between 2004 and 2014 at a single institution. A
      comparison of patient characteristics and outcomes was performed for 15 patients
      reconstructed with an SJF, 4 with CI, and 85 with GPU. RESULTS: Ten patients in
      the SJF group and 3 in the CI group underwent prior GPU with complications
      resulting in esophageal discontinuity. The CI group had significantly longer
      intensive care and overall hospital stays than either other group. Forty percent
      (SJF), 100% (CI), and 56% (GPU) experienced at least 1 complication during their
      postoperative hospitalization, most frequently bowel obstruction after SJF,
      anastomotic leak (CI), and pulmonary complications and arrhythmias (GPU). Rates
      of anastomotic leakage were 13% (GPU), 75% (CI), and 13% (SJF). Reoperation was
      required in 27% following SJF compared with 75% following CI and 19% following
      GPU. There was 1 CI graft failure and no SJF failures. CONCLUSIONS: The SJF is a
      reasonable first-line option for esophageal reconstruction, with comparable
      recovery, complication rate, and functional outcomes compared with the
      traditional GPU. When the stomach is unavailable, the SJF is superior to CI.

PMID- 29634502
TI  - Where is the "radical transformation" in nursing education?

PMID- 29634503
TI  - Effectiveness and safety of pharmacological sedation for aggressive or agitated
      adult patients in a prehospital emergency situation: a systematic review
      protocol.
AB  - REVIEW QUESTION/OBJECTIVE: The objective of this systematic review is to
      identify, evaluate and synthesize evidence on the effectiveness and safety of
      pharmacological sedation for aggressive or agitated adult patients in a
      prehospital emergency situation.

PMID- 29634504
TI  - Preventative interventions, protocols or guidelines for trauma patients at risk
      for cervical collar-related pressure ulcers: a scoping review protocol.
AB  - REVIEW OBJECTIVE/QUESTION: The objective of this review is to explore the
      existing literature related to preventative interventions, protocols or
      guidelines for trauma patients at risk for cervical collar-related pressure
      ulcers, examine and conceptually map the evidence, and identify any gaps in the
      literature.Specifically the review questions are.

PMID- 29634505
TI  - Effectiveness of discharge education on outcomes in acute coronary syndrome
      patients: a systematic review protocol.
AB  - REVIEW QUESTION: The question of this review is what is the effectiveness of
      discharge education on outcomes in acute coronary syndrome patients?

PMID- 29634506
TI  - Effectiveness of vibratory stimulation on needle-related procedural pain in
      children: a systematic review protocol.
AB  - REVIEW QUESTION/OBJECTIVE: The objective of this systematic review is to
      identify, evaluate and synthesize evidence on the effectiveness of vibratory
      stimulation to reduce needle-related procedural pain in children aged 18 years
      and under.The review will address the following question: Is vibratory
      stimulation effective in reducing needle-related procedural pain in children aged
      18 years and under, in comparison with no stimulation for needle-related
      procedures?

PMID- 29634507
TI  - Lung transplant recipients' experiences of and attitudes towards self-management:
      a qualitative systematic review protocol.
AB  - REVIEW QUESTION: The question for this review is: what are lung transplant
      recipients' experiences of and attitudes towards self-management?

PMID- 29634508
TI  - Effectiveness of phosphate binders in adult patients with end stage renal disease
      receiving hemodialysis: a systematic review protocol.
AB  - REVIEW QUESTION: The question of this review is what is the effectiveness of the
      use of phosphate binders on mortality and serum levels of phosphorus, calcium and
      intact parathyroid hormone in adult patients with end stage renal disease
      receiving hemodialysis?

PMID- 29634509
TI  - The concept of child-centered care in healthcare: a scoping review protocol.
AB  - REVIEW QUESTION/OBJECTIVE: The objective of this scoping review is to identify
      and evaluate the concept of child-centered care (CCC) in healthcare in order to
      achieve greater clarity on the concept and its applicability, benefits and
      potential to inform the evidence base of children's health care, policy and
      practice.The questions of this review are.

PMID- 29634510
TI  - Experiences of children exposed to parental post-traumatic stress disorder while
      growing up in military and veteran families: a systematic review protocol.
AB  - REVIEW QUESTION/OBJECTIVE: The objective of this review is to understand how
      parental Post-Traumatic Stress Disorder (PTSD) might impact children growing up
      in military and veteran families. The following question will guide and inform
      the review: What is the experience of children growing up in military families
      where the military or veteran parent is living with post-traumatic stress
      disorder?

PMID- 29634511
TI  - Older adults' experiences of patient involvement in transitional care: a
      qualitative systematic review protocol.
AB  - REVIEW QUESTION/OBJECTIVE: The objective of this review is to identify and
      synthesize older adult's experiences of patient involvement in transitional care
      between hospital and home. The purpose is to build theory to inform future
      research and clinical practice.The review will specifically address the following
      research questions.

PMID- 29634512
TI  - Effects of preoperative intrathecal morphine on postoperative intravenous
      morphine dosage: a systematic review protocol.
AB  - REVIEW QUESTION/OBJECTIVE: The purpose of this systematic review is to describe
      the effect of preoperative intrathecal morphine (ITM) on postoperative
      intravenous (IV) morphine dosage during the first postoperative day. This
      systematic review will compare the postoperative IV morphine dosage of patients
      receiving ITM plus morphine morphine-based patient-controlled analgesia (PCA), to
      patients receiving PCA morphine without ITM. This will establish the magnitude of
      the postoperative morphine sparing effect of ITM.This review aims to answer the
      following specific question: In adult abdominal and thoracic surgery patients
      undergoing general anesthesia (GA), what is the effect of ITM plus PCA morphine,
      compared to PCA morphine alone, on total IV morphine dosage (in milligrams)
      during the first 24 hours after surgery?

PMID- 29634513
TI  - Patient involvement interventions for older adults in transitional care between
      hospital and primary care: a scoping review protocol.
AB  - REVIEW QUESTION/OBJECTIVE: The objective of this scoping review is to identify
      and map existing evidence of patient involvement interventions for older adults
      in transitional care between hospital and primary care.The questions of this
      review are.

PMID- 29634514
TI  - Nursing quality indicator outcomes in hospitals with a Clinical Nurse Leader: a
      scoping review protocol.
AB  - REVIEW QUESTION/OBJECTIVE: What nursing quality indicator outcomes related to
      nosocomial infections have been identified in studies reporting upon care of
      patients by Clinical Nurse Leaders?The objective of this scoping review is to
      explore existing literature related to nursing quality indicator outcomes
      specific to nosocomial infections in studies reporting upon care of patients by
      Clinical Nurse Leaders, examine and conceptually map the evidence, and identify
      any gaps.

PMID- 29634515
TI  - Men's perceptions of the impact of the physical consequences of a radical
      prostatectomy on their quality of life: a qualitative systematic review.
AB  - OBJECTIVE: To identify men's perceptions of the impact of the physical
      consequences of a radical prostatectomy on their quality of life. INTRODUCTION:
      Prostate cancer is the most common male cancer and second most common cause of
      cancer death of men in the Western world. Compared to other prostate cancer
      treatments, trials report worse urinary incontinence and sexual function and
      similar bowel function among men with prostate-specific antigen detected prostate
      cancer who underwent radicalized prostatectomy. INCLUSION CRITERIA: This review
      included men of all ages and nationalities who had undergone a radical
      prostatectomy as treatment for any stage of prostate cancer. It considered
      studies that investigated:Any setting where the topic was addressed with
      participants meeting the inclusion criteria was included. The review considered
      studies that focused on qualitative data including, but not limited to:
      phenomenology, grounded theory, ethnography and action research. Studies were
      included if they reported results relating to one or more of the phenomena of
      interest. Studies not written in English were excluded. METHODS: The search
      strategy aimed to find published studies from six databases from database
      inception to November 2017. Methodological quality of studies was independently
      assessed by two reviewers using the standardized JBI Critical Appraisal Checklist
      for Qualitative Research. For data extraction, the standardized Joanna Briggs
      Institute System for the Unified Management, Assessment and Review of Information
      (JBI SUMARI) data extraction tool was used. A meta-aggregation was undertaken and
      the final synthesis of the findings was reached through discussion. Results are
      presented as five aggregated qualitative syntheses. RESULTS: Nineteen qualitative
      studies were included in the review. The five synthesized findings were:
      CONCLUSIONS:: Urinary incontinence and erectile dysfunction are significant side
      effects of radical prostatectomy which have a negative impact on men's quality of
      life for which they feel ill prepared, and physical and psychosocial support is
      essential.

PMID- 29634516
TI  - Effectiveness of complex falls prevention interventions in residential aged care
      settings: a systematic review.
AB  - OBJECTIVE: The objective of this review was to synthesize the best available
      evidence for the effectiveness of complex falls prevention interventions
      delivered at two or more of the following levels: resident, facility or
      organization, on fall rates in the residential aged care (RAC) population.
      INTRODUCTION: Preventing falls in the high risk RAC population is a common global
      goal with acknowledged complexity. Previous meta-analyses have not specifically
      addressed complexity, described as falls prevention intervention delivery at
      multiple levels of a RAC organization, to determine its effect on fall outcomes.
      INCLUSION CRITERIA: The current review considered studies that included
      participants who were aged 65 years and over residing in long-term care settings
      providing 24-hour supervision and/or care assistance.Studies that evaluated
      complex falls prevention interventions delivered by single discipline or
      multidisciplinary teams across at least two or all of the following levels:
      residents, RAC facility and RAC organization were eligible. Experimental study
      designs including randomized controlled trials, controlled clinical trials and
      quasi-experimental trials that reported on measures related to fall incidence
      were considered, namely, rate of falls (expressed as the number of falls per 1000
      occupied bed days), the number of participants who became fallers (expressed as
      the number of participants who fell once or more) and the rate of injurious falls
      (expressed as the number of falls with injury per 1000 occupied bed days).
      METHODS: A three-step search strategy was undertaken, commencing with an initial
      scoping search of MEDLINE and CINAHL databases prior to an extensive search of
      all relevant published literature, clinical trial registries and gray literature.
      Two independent reviewers assessed selected studies for methodological validity
      using the standardized critical appraisal instrument from the Joanna Briggs
      Institute System for the Unified Management, Assessment and Review of Information
      (JBI SUMARI). Data were extracted from the selected studies using the
      standardized data extraction tool from JBI SUMARI. Quantitative data were pooled
      in statistical meta-analysis for rate of falls, the number of participants who
      became fallers and the rate of injurious falls. Meta-analysis was conducted using
      a random-effect model with heterogeneity assessed using the standard Chi-squared
      and I index. Where statistical pooling was not possible, study findings were
      presented in narrative form. RESULTS: Twelve studies were included in this review
      with seven being eligible for meta-analysis. Complex falls prevention
      interventions delivered at multiple levels in RAC populations did not show a
      significant effect in reducing fall rates (MD = -1.29; 95% CI [-3.01, 0.43]), or
      the proportion of residents who fell (OR = 0.76; 95% CI [0.42, 1.38]). However, a
      sensitivity analysis suggested complex falls prevention interventions delivered
      with additional resources at multiple levels had a significant positive effect in
      reducing fall rates (MD = -2.26; 95% CI [-3.72, -0.80]). CONCLUSIONS: Complex
      falls prevention interventions delivered at multiple levels in the RAC population
      may reduce fall rates when additional staffing, expertise or resources are
      provided. Organizations may need to determine how resources can be allocated to
      best address falls prevention management. Future research should continue to
      investigate which combinations of multifactorial interventions are effective.

PMID- 29634517
TI  - Action research in the healthcare field: a scoping review.
AB  - OBJECTIVE: This scoping review aimed to explore international literature related
      to the application of action research in studies in the healthcare context.
      INTRODUCTION: Action research is an approach that involves collaboration to
      develop a process through knowledge building and social change. Several
      viewpoints of action research have been introduced as the different traditions of
      developed action research. To develop a coherent process, researchers have to
      posit their worldviews and theoretical framework and align these with the
      research aims and procedures, and local transformation needs. This diversity
      leads to a variety of action research practices in healthcare. Particularly, in
      this review, we raised the need for examining participants' experiences and
      changes related to the action research process. INCLUSION CRITERIA: This scoping
      review considered studies that included any professional healthcare provider,
      patient or recipient of healthcare products or services involved in action
      research. Studies that used the action research methodology in the healthcare
      context were included. All quantitative and qualitative studies were considered.
      The quantitative component considered experimental and epidemiological studies,
      whereas the qualitative component considered studies that focused on qualitative
      data. METHODS: A three-step search strategy was used in this review. MEDLINE,
      CINAHL, Web of Science, Social Sciences, ERIC, PsycINFO, Health Source,
      ScienceDirect, Wiley and SciELO databases were searched with no publication date
      limitation. Studies published in English, Portuguese and Spanish were included.
      The data were extracted using a charting table, which was developed to record key
      information from sources relevant to the review question. The findings were
      descriptively presented, with tables and figures to support the data when
      appropriate. RESULTS: We included 124 studies with different aims and procedures.
      The levels of participation ranged from no real input into or influence on the
      research process to democratic knowledge sharing and collective understanding.
      The action research processes occurred in diverse settings in the healthcare
      context, and participants with different objectives and demands took part in the
      research.From study objectives, knowledge building, and social change data, we
      developed three domains and categorized the studies. In general, Europe and
      Australia published more studies in the organizational domain and mainly had
      healthcare stakeholders as participants. North America published more studies in
      the individual domain, and Latin America, the continent with a higher percentage
      of publications, published studies that were more frequently related to the
      collective domain. Asia and Africa did not have a consistent number of
      publications. There was a major repercussion on the health promotion perspective
      in North America and Latin America. CONCLUSIONS: There are several ways of
      conducting action research in healthcare that consider the researcher's aims and
      theoretical assumptions. Further qualitative systematic review questions may
      arise from the results and conclusions of this scoping review.

PMID- 29634518
TI  - Treatment of nipple pain in breastfeeding women in the postpartum ward of the
      University Hospital of Lausanne: a best practice implementation project.
AB  - INTRODUCTION: Breast milk represents the optimal nutrition for a child and is
      recommended during the first six months. However, nipple pain often occurs during
      the onset of lactation and may affect breastfeeding and exclusive breastfeeding
      duration rates. Multiple treatments are available in the postpartum units of the
      Lausanne University Hospital (CHUV, Lausanne, Switzerland) and are used
      empirically, according to caregiver preferences. OBJECTIVES: The aim of this
      project is to implement a care plan for nipple pain according to best
      recommendations and evidence-based studies. METHODS: The project was developed
      using the Joanna Briggs Institute framework and Practical Application of Clinical
      Evidence System (JBI-PACES). Five audit criteria were used in pre- and post
      audits to observe any changes in compliance with the recommendations. The Getting
      Research into Practice (GRiP) was used between audits to identify stakeholders,
      barriers and facilitators of the project. RESULTS: Compliance in four criteria
      improved, with no increase in pain experienced by breastfeeding mothers. More
      women received adequate information (from 47% to 64%) and support (from 47% to
      58%). Each item under criteria 2 (adequate information) and 3 (adequate support)
      showed improvement. The adequate management of nipple pain also increased from 8%
      to 31%. However, it remains an important issue to consider. CONCLUSIONS: Despite
      the limitations associated with small samples, the results of this project show
      that implementation of best practice is possible, even though it involved the
      withdrawal of unnecessary treatment. Another evaluation is necessary in the
      future to consolidate and improve these results.

PMID- 29634519
TI  - Management of dexamethasone-induced hyperglycemia in patients undergoing
      chemotherapy in an outpatient setting: a best practice implementation project.
AB  - OBJECTIVES: The objective of this project was to implement best practice in an
      outpatient clinical setting in order to increase both nursing staff and patients'
      knowledge and awareness on the importance of blood sugar management during
      chemotherapy and to show that through compliance with best practice, the
      incidence of dexamethasone-induced hyperglycemia during chemotherapy can be
      minimized. INTRODUCTION: Steroid-induced hyperglycemia is a commonly neglected
      symptom in cancer treatment, contributing to poor patient prognosis and extended
      hospital stay. Evidence shows that controlled blood sugar during chemotherapy is
      associated with improved patient outcomes and better tolerance to cancer
      treatment. For the purpose of this paper steroid-induced hyperglycemia will be
      referred to as dexamethasone-induced hyperglycemia. METHODS: This project
      utilized the Joanna Briggs Institute Practical Application of Clinical Evidence
      System (JBI-PACES) and Getting Research into Practice (GRiP) audit tools to
      promote compliance in the clinical setting. Thirty patients participated in the
      audit, which was executed by nursing staff in the Medical Oncology Outpatient
      Unit at the Cancer Ambulatory and Community Health Support Department at the
      Canberra Hospital. RESULTS: The baseline audit revealed large gaps between best
      practice and current practice. This underlined the need for more education for
      both nursing staff and patients. Other barriers such as the absence of assessment
      and documentation by the clinicians and the minimum number of potential referrals
      to the diabetes educator were addressed by encouraging patients to speak about
      their diabetes, and also in the development of a simplified referral process in
      order to have patients reviewed by the Diabetes Educator in a timely manner.
      There were significant improvements after more information sessions were held and
      more resources made available to both nursing staff and patients, but there were
      also minimal to zero compliance drop on parts of the follow-up audit.
      CONCLUSIONS: In an attempt to improve patient outcome during chemotherapy, the
      project has succeeded in changing the attitude towards blood sugar control, and
      in increasing knowledge and awareness of dexamethasone-induced hyperglycemia
      among nursing staff and patients. However, there is room for improvement, based
      on the results of the implementation project. Future audits are planned to ensure
      sustainability.

PMID- 29634520
TI  - Why Aren't There More Female Pain Medicine Physicians?
AB  - Despite a growing awareness about the importance of gender equity and the rising
      number of women in medicine, women remain persistently underrepresented in pain
      medicine and anesthesiology. Pain medicine ranks among the bottom quartile of
      medical specialties in terms of female applicants, female trainees, and
      proportion of female practitioners. Female pain medicine physicians are also
      notably disadvantaged compared with their male colleagues in most objective
      metrics of gender equity, which include financial compensation, career
      advancement, public recognition, and leadership positions. Increased gender
      diversity among pain medicine physicians is vital to fostering excellence in pain
      research, education, and clinical care, as well as creating a high-quality work
      environment. Pain medicine stands at a crossroads as a specialty, and must
      examine reasons for its current gender gap and consider a call to action to
      address this important issue.

PMID- 29634521
TI  - Sex-Mediated Response to the Beta-Blocker Landiolol in Sepsis: An Experimental,
      Randomized Study.
AB  - OBJECTIVES: To investigate any gender effect of the beta-1 adrenergic blocker,
      landiolol, on cardiac performance and energy metabolism in septic rats, and to
      explore the expression of genes and proteins involved in this process. DESIGN:
      Randomized animal study. SETTING: University research laboratory. SUBJECTS: Male
      and female Wistar rats. INTERVENTIONS: One hour after cecal ligation and
      puncture, male and female rats were randomly allocated to the following groups:
      sham male, cecal ligation and puncture male, cecal ligation and puncture +
      landiolol male, sham female, cecal ligation and puncture female, and cecal
      ligation and puncture + landiolol female. Cardiac MRI was carried out 18 hours
      after cecal ligation and puncture to assess in vivo cardiac function. Ex vivo
      cardiac function measurement and P magnetic resonance spectroscopy were
      subsequently performed using an isovolumic isolated heart preparation. Finally,
      we assessed cardiac gene and protein expression. MEASUREMENTS AND MAIN RESULTS:
      In males, landiolol increased indexed stroke volume by reversing the indexed end
      diastolic volume reduction without affecting left ventricle ejection fraction. In
      females, landiolol did not increase indexed stroke volume and indexed end
      diastolic volume but decreased left ventricle ejection fraction. Landiolol had no
      effect on ex vivo cardiac function and on high-energy phosphate compounds. The
      effect of landiolol on the gene expression of natriuretic peptide receptor 3 and
      on protein expression of phosphorylated-AKT:AKT ratio and endothelial nitric
      oxide synthase was different in males and females. CONCLUSIONS: Landiolol
      improved the in vivo cardiac performance of septic male rats while deleterious
      effects were reported in females. Expression of natriuretic peptide receptor 3,
      phosphorylated-AKT:AKT, and endothelial nitric oxide synthase are signaling
      pathways to investigate to better understand the sex differences in sepsis.

PMID- 29634522
TI  - Continuous Pectoral Fascia Blocks for Postoperative Analgesia After Median
      Sternotomy: A Case Report.
AB  - We report a novel case of a patient who presented for aortic valve replacement
      via median sternotomy. Bilateral continuous pectoral fascia blocks were placed to
      provide postoperative analgesia. Both numerical rating scale pain scores and
      opioid consumption after surgery were suggestive of analgesic benefit.

PMID- 29634523
TI  - Parturient With Barnes Syndrome (Thoracolaryngopelvic Dysplasia) Undergoing
      Cesarean Delivery of a Neonate With Barnes Syndrome: A Case Report.
AB  - This case describes a parturient with Barnes syndrome, a rare disorder
      characterized by subglottic stenosis, thoracic dystrophy, and small pelvic inlet,
      who underwent cesarean delivery of a neonate diagnosed with Barnes syndrome. Live
      simulation training was performed by multidisciplinary team to prepare for the
      spinal anesthetic, personnel flow between 2 operating rooms, and management of
      various airway scenarios for the newborn. After delivery, the neonate underwent
      laryngoscopy-bronchoscopy with successful intubation in the operating room
      because of labored breathing. Airway evaluation revealed subglottic stenosis,
      tracheomalacia/bronchomalacia. Collaboration among perinatologists,
      obstetric/pediatric anesthesiologists, pediatric head and neck surgeons, and
      neonatologists was integral to perioperative management of both the mother and
      child.

PMID- 29634524
TI  - Anterior Cutaneous Nerve Entrapment Syndrome in a Pediatric Patient Previously
      Diagnosed With Functional Abdominal Pain: A Case Report.
AB  - Chronic abdominal pain is common in children and adolescents but challenging to
      diagnose, because practitioners may be concerned about missing serious occult
      disease. Abdominal wall pain is an often ignored etiology for chronic abdominal
      pain. Anterior cutaneous nerve entrapment syndrome causes abdominal wall pain but
      is frequently overlooked. Correctly diagnosing patients with anterior cutaneous
      nerve entrapment syndrome is important because nerve block interventions are
      highly successful in the remittance of pain. Here, we present the case of a
      pediatric patient who received a diagnosis of functional abdominal pain but
      experienced pain remittance after receiving a trigger-point injection and
      transverse abdominis plane block.

PMID- 29634525
TI  - It Is Not Always the Epidural: A Case Report of Anterior Spinal Artery Ischemia
      in a Trauma Patient.
AB  - Motor vehicle collisions impact millions of people annually resulting in
      multiinjury trauma. Anesthesiologists are consulted for rib fracture analgesia to
      improve respiratory mechanics and prevent intubation. This report describes a
      trauma patient who developed hypotension and lower extremity weakness after
      epidural placement for multiple rib fractures. Initially, hypotension was
      attributed to neuraxial sympathectomy. However, physical examination also
      indicated anterior spinal artery ischemia. Regional anesthesia and acute pain
      teams must be able to both identify contraindications and complications of
      regional techniques and discern when complications are not a result of regional
      interventions to initiate prompt management and definitive care.

PMID- 29634526
TI  - Serial Gastric Ultrasound to Evaluate Gastric Emptying After Prokinetic Therapy
      With Domperidone and Erythromycin in a Surgical Patient With a Full Stomach: A
      Case Report.
AB  - Fasting guidelines are used to prevent perioperative aspiration but they are only
      reliable in healthy elective patients. Point-of-care gastric ultrasound allows
      qualitative and quantitative evaluation of gastric contents at the bedside. This
      case report describes the use of serial gastric point-of-care ultrasound to
      evaluate the effect of prokinetic therapy with domperidone and erythromycin in an
      elective surgical patient with multiple comorbidities who presented with a full
      stomach.

PMID- 29634527
TI  - Two-Level Continuous Thoracic Paravertebral Nerve Blocks Providing Opioid-Free
      Postoperative Analgesia After Latissimus Dorsi Flap Breast Reconstruction: A Case
      Report.
AB  - We present the case of a 55-year-old woman undergoing a delayed latissimus dorsi
      flap breast reconstruction after a simple mastectomy for breast cancer.
      Preoperatively, 2 unilateral paravertebral catheters were placed at T3/4 and T7/8
      for postoperative analgesia. Postoperatively, ropivacaine 0.2% was infused until
      the day of discharge on postoperative day 2. The patient had excellent
      postoperative analgesia and required no opioids or other analgesics through
      postoperative day 10. We report that multilevel paravertebral nerve blockade
      could represent an opioid-sparing alternative for postoperative analgesia for
      latissimus dorsi flap breast reconstruction patients.

PMID- 29634528
TI  - Safe Use of Epidural Analgesia in a Parturient With Spinocerebellar Ataxia: A
      Case Report.
AB  - A 28-year-old, gravida 7, para 4 woman with medical history of sickle cell trait
      presented to labor and delivery at 39 weeks of gestation for rupture of
      membranes. The patient had a history of suspected spinocerebellar ataxia with
      incomplete workup before the current admission. The patient requested epidural
      analgesia for labor. Epidural was placed at L3-L4 interspace without any
      complications and the rest of the labor was uneventful. Magnetic resonance
      imaging of the brain was performed after the delivery and the diagnosis of
      spinocerebellar ataxia was confirmed. The patient's neurological status remained
      stable after the procedure.

PMID- 29634529
TI  - Fiberoptic-Guided Use of an Airway Exchange Catheter During Exchange of a Kinked
      King LTS-D Laryngeal Tube for an Endotracheal Tube: A Case Report.
AB  - The use of supraglottic airway devices such as the King LTS-D laryngeal tube has
      increased in the prehospital setting because of their relative ease of successful
      insertion, even in the hands of inexperienced providers. However, these devices
      have their own associated complications. In patients with a known or suspected
      difficult airway, supraglottic airway device exchanges should occur under
      controlled conditions using an airway exchange catheter, preferably under direct
      visualization with a flexible fiberoptic bronchoscope. We report unanticipated
      difficulties with supraglottic airway exchange caused by a kinked King LTS-D
      laryngeal tube.

PMID- 29634530
TI  - Treatment of Transradial Angiogram Catheter Entrapment by Axillary Artery Spasm
      With Supraclavicular Brachial Plexus Block: A Case Report.
AB  - We present a 36-year-old female patient who underwent transradial cerebrovascular
      angiography because of acute putaminal hemorrhage. Catheter entrapment occurred
      with severe pain in the right upper arm proximal to the elbow. A subclavian
      artery angiogram by way of a transfemoral crossover catheter revealed severe
      vasospasm in the axillary artery distal to the branch point between it and the
      posterior brachial circumflex artery. Diazepam 5 mg intravenously (IV) through a
      peripheral catheter, lidocaine 0.5% 5 mL injected subcutaneously, and lidocaine
      2% 4 mL IV isosorbide dinitrate 2 mg IV through the angiographic crossover
      catheter failed to relieve the pain and catheter entrapment. An ultrasound-guided
      supraclavicular brachial plexus block relieved both within 3 minutes. In the
      past, general anesthesia would have been administered.

PMID- 29634531
TI  - Oropharyngeal Stenosis Leading to an Unanticipated Difficult Airway in a Patient
      After Uvulopalatopharyngoplasty: A Case Report and Review of the Literature.
AB  - Oropharyngeal stenosis can manifest as a rare complication after surgery for
      obstructive sleep apnea or tonsillectomy. Scar tissue formation from
      oropharyngeal stenosis may impede tracheal intubation or laryngeal mask airway
      insertion. We report the case of an asymptomatic adult woman found to have
      oropharyngeal stenosis after induction of anesthesia and discuss the management
      of this challenging scenario. We also contrast oropharyngeal stenosis with
      nasopharyngeal stenosis, another rare complication of uvulopalatopharyngoplasty.

PMID- 29634532
TI  - Traumatic Tracheobronchial Laceration Causing Complete Tracheal Resection:
      Challenges of Anesthetic Management.
AB  - We report the case of a 9-year-old girl who sustained blunt trauma to the chest
      and presented for emergent repair of a complete tracheobronchial laceration.
      Tracheobronchial laceration is potentially life threatening. While conservative
      management has been described for simple tears, more complex injuries require
      surgical repair. We discuss the anesthetic challenges, airway management, and
      ventilation options for surgical repair in a child with a complex laceration
      involving the tracheobronchial tree.

PMID- 29634533
TI  - Linezolid-Induced Lactic Acidosis Sets Stage for Surgery to Rule Out Mesenteric
      Ischemia: A Case Report.
AB  - An 81-year-old woman with extensive peripheral vascular and coronary artery
      disease was admitted to the intensive care unit with a deep heel abscess and
      urinary tract infection. When cultures from the heel ulcer yielded vancomycin
      resistant enterococci, she was started on the antibiotic linezolid. After several
      days of intravenous linezolid therapy, she developed severe lactic acidosis (pH
      6.89) and elevation of pancreatic enzymes. An emergent exploratory laparotomy was
      performed to rule out mesenteric ischemia. Findings from the laparotomy were
      negative, and after elimination of other differential diagnoses, the metabolic
      acidosis was ultimately attributed to linezolid. Acidosis resolved after
      discontinuation of linezolid.

PMID- 29634534
TI  - Ultrasound Imaging of the Inferior Vena Cava to Confirm Correct Guidewire
      Placement After Femoral Venous Cannulation in Critically Ill Neonates: A Case
      Report.
AB  - Ultrasound-guided femoral venous cannulation is frequently performed in neonates.
      Identification of femoral vessels under ultrasound navigation is unreliable and
      time consuming in hemodynamically unstable neonates with feeble femoral arterial
      pulse. Confirming the guidewire placement in a femoral vein is a crucial step for
      preventing inadvertent femoral artery dilation, which may be a challenging task
      in an emergency situation. We describe 2 incidents wherein guidewires placed via
      femoral veins in neonates were detected in the inferior vena cava on abdominal
      ultrasound. We advocate abdominal inferior vena cava imaging to confirm the
      correct placement of a guidewire placed via femoral vein in emergency situations.

PMID- 29634535
TI  - Focused Cardiac Ultrasound Determines Cause of Cardiovascular Collapse During
      Thoracic Surgery in a Patient With Undiagnosed Pulmonary Hypertension: A Case
      Report.
AB  - Patients with severe pulmonary hypertension (PHT) represent a high-risk
      population when undergoing noncardiac surgery. During thoracic surgery with 1
      lung ventilation, atelectasis of the operative lung, and frequently associated
      hypoxemia, is likely to exacerbate PHT and precipitate acute right ventricular
      failure. We present a patient with previously undiagnosed PHT who suffered 2
      cardiac arrests during emergent thoracic surgery for empyema. After successful
      resuscitation in the operating room, she subsequently required prolonged
      venoarterial extracorporeal membrane oxygenation. Focused transthoracic
      echocardiography to evaluate cardiac function was critical in the diagnosis of
      PHT and subsequent treatment with sildenafil and nifedipine when discharged from
      the hospital.

PMID- 29634536
TI  - Intraoperative Venovenous Extracorporeal Membrane Oxygenation as Rescue for a
      Patient With an Inhalational Burn and Iatrogenic Upper Airway Injury: A Case
      Report.
AB  - Venovenous extracorporeal membrane oxygenation (VV-ECMO) is a well-established
      alternative oxygenation method for critically ill patients. A 58-year-old male
      was transferred to our level 1 trauma and burn center after sustaining an
      inhalational injury from a carburetor explosion, with subsequent iatrogenic
      tracheal injury and emergent cricothyrotomy before arrival. During attempted
      surgical airway stabilization, our ability to ventilate and oxygenate was
      compromised. Intraoperative VV-ECMO enabled rescue from severe hypoxemia and
      subsequent recovery without lasting neurologic sequelae. This case highlights the
      utility of VV-ECMO for acute intraoperative rescue.

PMID- 29634537
TI  - Vitamin C for Vasoplegia After Cardiopulmonary Bypass: A Case Series.
AB  - Cardiac vasoplegia remains a significant contributor of morbidity and mortality
      in cardiac surgery patients after cardiopulmonary bypass. Effective therapeutic
      options for vasopressor-refractory vasoplegia are limited. We report 3 patients
      in whom we administered high-dose intravenous ascorbic acid (vitamin C), a
      cofactor for endogenous catecholamine synthesis, to treat vasoplegia refractory
      to epinephrine, vasopressin, and norepinephrine after surgery requiring
      cardiopulmonary bypass. Reductions in vasopressor requirements were observed in
      all 3 patients, and, in 2 patients, norepinephrine was completely discontinued
      within 24 hours. Ascorbic acid is a novel potential therapeutic option for
      cardiac vasoplegia that warrants rigorous prospective studies.

PMID- 29634538
TI  - Ruptured Giant Coronary Artery Aneurysm With Coronary Artery to Pulmonary Artery
      Fistula Presenting as Cardiac Tamponade Diagnosed by Intraoperative
      Transesophageal Echocardiography: A Case Report.
AB  - A 63-year-old woman presented with cardiac tamponade because of a ruptured giant
      left anterior descending coronary artery aneurysm with a fistula to the main
      pulmonary artery. The diagnosis was made intraoperatively during an emergent
      subxiphoid pericardial window using transesophageal echocardiography and
      confirmed by intraoperative coronary angiography. Because of this prompt
      diagnosis, the patient was successfully managed with immediate surgical repair of
      the aneurysm and fistula.

PMID- 29634539
TI  - Desmopressin Reverses Overly Rapid Serum Sodium Correction in a Hyponatremic
      Patient Undergoing Living Donor Liver Transplantation: A Case Report.
AB  - Patients with end-stage liver disease are often hyponatremic due to multiple
      physiological processes associated with hepatic failure. For severely
      hyponatremic patients undergoing liver transplantation, intraoperative management
      of serum sodium concentration ([Na]s) is challenging. [Na]s tends to increase
      during transplantation by the administration of fluids with higher sodium
      concentration than the patient's [Na]s. An overly rapid increase in [Na]s (>1
      mEq.L.hour) is difficult to avoid and increases the risk of serious perioperative
      complications. We report the successful use of intravenous desmopressin to
      reverse an overly rapid rise in [Na]s during living donor liver transplantation.

PMID- 29634540
TI  - Perioperative Extracorporeal Cardiopulmonary Resuscitation: The Defibrillator of
      the 21st Century?: A Case Report.
AB  - Veno-arterial-extracorporeal membrane oxygenation (ECMO) for cardiopulmonary
      resuscitation (ECMO-CPR) has been recommended by new resuscitation guidelines in
      the United Kingdom. Our recently established yet unfunded ECMO-CPR service has
      thus far treated 6 patients, with 3 making a good recovery. One patient suffered
      a catastrophic perioperative complication through glycine absorption and we are
      in no doubt that she would not have survived without ECMO. We argue for a
      pragmatic approach to funding of ECMO-CPR because observational evidence suggests
      superiority over traditional resuscitation and there exists major methodological
      and ethical barriers to randomized controlled studies. We also call for high
      quality observational evidence in the perioperative setting.

PMID- 29634541
TI  - Fluctuating Pulse Oximetry Readings in an Adolescent With Hemoglobin Bibba: A
      Case Report.
AB  - Hemoglobinopathies caused by unstable hemoglobins represent a wide group of
      diseases that include hemoglobin Bibba. Hemoglobin instability may cause chronic
      hemolytic anemia and conformational changes in hemoglobin that affect affinity
      for oxygen and absorption of wavelengths of light used in pulse oximetry devices.
      We report the case of an adolescent with hemoglobin Bibba and alpha-thalassemia.
      SpO2 was unexpectedly low despite stable vital signs when his hemoglobin was
      closer to 10 g/dL and normal when his hemoglobin was lower, presumably when there
      was less unstable hemoglobin because of hemolysis.

PMID- 29634542
TI  - Sphenopalatine Ganglion Block to Treat Shoulder Tip Pain After Thoracic Surgery:
      Report of 2 Cases.
AB  - Shoulder tip pain may occur after thoracic surgical procedures. The pain is
      caused by diaphragmatic irritation and is referred to the shoulder. Shoulder tip
      pain is often resistant to treatment with conventional analgesics. The
      sphenopalatine ganglion block has been described to manage many painful
      conditions. We report here the first use of this block to treat shoulder tip pain
      in 2 thoracic surgical patients. In both patients, the block produced rapid and
      sustained relief of the shoulder tip pain. We suggest that sphenopalatine
      ganglion block be considered to treat postoperative shoulder tip pain after
      thoracic surgical procedures.

PMID- 29634543
TI  - Pocket-Size Ultrasound Examination: Assessment of Gastric Contents.

PMID- 29634544
TI  - Successful Relief of Back Pain From Baastrup Disease (Kissing Spines) by
      Interspinous Radiofrequency Lesioning: A Case Report.
AB  - Baastrup disease is a condition where spinous processes form painful
      pseudoarticulations. We present a patient with midline axial back pain consistent
      with Baastrup disease confirmed by computed tomography, which revealed
      degenerative changes along the opposing surfaces of the spinous processes at L1-2
      and L2-3. Local anesthetic and steroid interspinous injections lost their
      effectiveness over time. She underwent successful interspinous radiofrequency
      lesioning, which has not been previously described in the literature. At 4 months
      follow-up, she reported complete pain relief.

PMID- 29634545
TI  - Intraoperative Use of Desmopressin for Treatment of Profound Hyponatremia in the
      Setting of Emergency Surgery: A Case Report.
AB  - Correction of profound hyponatremia requires careful planning and close
      monitoring to reduce the risks of neurologic injury. Although there are various
      suggested treatment strategies in the setting of a medical ward or intensive care
      unit, reports of intraoperative management to prevent rapid increases in serum
      sodium are lacking. We present a case of profound hyponatremia of 102 mmol/L in a
      patient who required emergent operative repair for bowel obstruction. This is the
      first case to our knowledge that demonstrates a perioperative fluid and
      desmopressin treatment strategy to prevent overly rapid changes of sodium
      concentration in a patient with severe hyponatremia.

PMID- 29634546
TI  - When Guidelines Fail: Euglycemic Diabetic Ketoacidosis After Bariatric Surgery in
      a Patient Taking a Sodium-Glucose Cotransporter-2 Inhibitor: A Case Report.
AB  - A 42-year-old woman with diabetes mellitus type 2 treated with the sodium-glucose
      cotransporter-2 inhibitor canagliflozin underwent elective bariatric gastric
      bypass. The canagliflozin was held for 24 hours preoperatively. She
      physiologically decompensated on postoperative day 2. Ultimately, she was
      diagnosed with euglycemic diabetic ketoacidosis that required intensive care
      management. This diagnosis was challenging to make as the patient never became
      hyperglycemic. We use this case to discuss the pharmacology and potential risk of
      perioperative sodium glucose cotransporter-2 inhibitor administration and to
      advocate for revision of current guidelines regarding the perioperative
      management of these agents.

PMID- 29634547
TI  - Celiac Plexus Block as a Predictor of Surgical Outcome for Sympathetically
      Mediated Abdominal Pain in a Case of Suspected Median Arcuate Ligament Syndrome:
      A Case Report.
AB  - Median arcuate ligament syndrome (MALS), also known as celiac artery compression
      syndrome, is an uncommon condition classically characterized by chronic abdominal
      pain, weight loss, and abdominal bruit. Chronic mesenteric ischemia caused by
      intermittent compression of the celiac artery by the MAL provokes upper abdominal
      pain that is sympathetically mediated via the celiac plexus. Because it is a
      diagnosis of exclusion, diagnosis of MALS in the clinical setting is typically
      challenging. We present an atypical case which highlights the utility of celiac
      plexus block as both an assistant diagnostic tool and a predictor of surgical
      outcomes for suspected MALS.

PMID- 29634548
TI  - Treatment of Postherpetic Neuralgia With Intravenous Administration of Zinc
      Sulfate: A Case Report.
AB  - Gabapentinoids (gabapentin and pregabalin) are first-line drugs for postherpetic
      neuralgia (PHN), but some PHN patients have inadequate therapeutic response. Zinc
      deficiency has been identified as a risk factor for PHN. Zinc can alleviate pain
      through binding to Ca(v)3.2 T-channels and N-methyl-D-aspartate receptors.
      Mechanisms of gabapentinoids on neuropathic pain include inhibiting N-methyl-D
      aspartate receptors and calcium channels. The aforementioned findings provide a
      molecular pain-relieving basis for zinc supplements as an add-on therapy to
      pregabalin. We report 2 zinc-deficient PHN patients who received zinc sulfate
      intravenously as an add-on therapy to pregabalin and responded well.

PMID- 29634549
TI  - Treatment of Refractory Intraoperative Hypoxemia After Trauma With Venovenous
      Extracorporeal Membrane Oxygenation: A Case Report.
AB  - Extracorporeal membrane oxygenation has emerged as a treatment of choice for
      refractory hypoxemia in the intensive care unit. Severe hypoxemia unresponsive to
      conventional lung-protective mechanical ventilation could also occur in the
      operating room from severe bronchospasm, pulmonary contusions, or acute
      respiratory distress syndrome. We report a case of acute hypoxic respiratory
      failure in an adolescent with blunt chest trauma that was successfully managed
      with the intraoperative initiation of venovenous extracorporeal membrane
      oxygenation during the initial damage control surgery.

PMID- 29634550
TI  - Ultrasound-Guided Pericapsular Hip Joint Alcohol Neurolysis for the Treatment of
      Hip Pain: A Case Report of a Novel Approach.
AB  - Severe pain after a hip fracture commonly delays hospital discharge and poses
      significant nursing problems in patients who are not surgical candidates. We
      present ultrasound-guided pericapsular hip alcohol neurolysis of the articular
      branches of the femoral and obturator nerves as a novel approach in the treatment
      of severe pain after hip fracture. This technique provided excellent pain relief
      in a 94-year-old patient with intertrochanteric hip fracture until her death 2
      months later.

PMID- 29634551
TI  - Transfusion-Associated Circulatory Overload as a Result of Plasma Transfusion to
      Correct International Normalized Ratio Before an Invasive Procedure: A Case
      Report.
AB  - Plasma transfusion is commonly used to correct elevated international normalized
      ratio (INR) before invasive procedures. A 54-year-old woman presented to the
      emergency department with abdominal pain. Workup revealed Streptococcus
      pneumoniae peritonitis. Her hospitalization was complicated by respiratory
      failure, fluid overload, atrial fibrillation, and acute kidney injury. Patient
      underwent 2 paracentesis (9 L removed). Four units of plasma were transfused to
      correct an INR of 3.0 (goal 1.5) for a transjugular intrahepatic portosystemic
      shunt procedure. INR remained at 1.9, and she developed acute pulmonary edema and
      died within 24 hours. Prothrombin complex concentrates may have been a more
      appropriate treatment option in this case.

PMID- 29634552
TI  - Naloxegol to Treat Constipation in a Patient Taking Opioids for Cancer Pain: A
      Case Report.
AB  - Opioid-induced constipation (OIC) is a common gastrointestinal adverse effect of
      opioids, which can severely affect compliance and adherence to pain medication
      regimens and quality of life. Naloxegol has demonstrated efficacy against OIC in
      several studies involving patients with nonmalignant chronic pain. Here we report
      efficacy and tolerability of naloxegol in a 68-year-old patient with metastatic
      lung cancer and severe pain, treated with opioids, who presented with OIC
      resistant to traditional measures. Addition of naloxegol produced rapid
      improvement in his OIC symptoms and no apparent adverse effects while taking
      extended-release morphine 130 mg orally every 12 hours.

PMID- 29634553
TI  - Transversalis Fascia Plane Block for the Treatment of Chronic Postherniorrhaphy
      Inguinal Pain: A Case Report.
AB  - Chronic neuropathic pain is a well-recognized complication of inguinal hernia
      repair. We report a 47-year-old man suffering from chronic neuropathic
      postherniorrhaphy pain. Planned ilioinguinal and iliohypogastric nerve blocks
      were not possible because excessive surgical scarring had distorted the
      sonoanatomy. We therefore performed transversalis fascia plane block with local
      anesthetic and steroid that resulted in long-term pain relief. This block has
      been successfully used in the past for providing postoperative analgesia in the
      L1 dermatome, but its role in chronic pain is unreported.

PMID- 29634554
TI  - Regional Anesthesia in the Setting of Arm Replantation: A Case Report.
AB  - The perioperative implementation of continuous peripheral nerve blocks is poorly
      described within the literature for replantation surgeries beyond digital
      replantation. The management of replantation patients presents a challenging
      balance between pain control and limb perfusion. We report the successful use of
      a continuous interscalene catheter in a therapeutically anticoagulated patient
      after midshaft humerus arm replantation. The benefits of the continuous
      peripheral nerve block for the patient included improved pain control and
      potentially improved limb perfusion making it a valuable component of this
      patient's treatment.

PMID- 29634555
TI  - A Subarachnoid Hemorrhage Presenting as Massive Nasopharyngeal Bleeding: A Case
      Report.
AB  - Patients who present with a subarachnoid hemorrhage may have more than 1
      intracranial aneurysm at risk, which may not be appreciated until a subsequent
      aneurysmal bleeding event occurs. We describe a patient who underwent successful
      aneurysmal clipping, but later presented urgently with large-volume epistaxis 48
      hours after the procedure. After successful intubation of the patient, subsequent
      angiographic imaging determined that the massive intranasal/oral hemorrhage was
      due to bleeding through the former operative site, from rupture of a previously
      unrecognized aneurysm. This series of events demonstrates the importance of
      selecting the most at-risk aneurysm for surgical intervention.

PMID- 29634556
TI  - Anesthesia for Pygopagus Conjoined Twins During Single-Twin and Simultaneous
      Pneumoperitoneum: A Case Report.
AB  - We present the case of the first stage of separation of 9-month-old pygopagus
      conjoined twins who demonstrated minimal shared vasculature on preoperative
      imaging and no cross-sedation or cross-neuromuscular blockade during separate
      inductions of anesthesia. Laparoscopy was implemented in 1 twin at a time, then
      in both twins simultaneously. Despite insufflation of a single-twin's abdomen,
      both twins demonstrated hypercapnia and signs of a concomitant respiratory
      acidosis because of carbon dioxide diffusion through a shared peritoneal
      membrane. This is the first documented case of simultaneous laparoscopy-induced
      pneumoperitoneum in pygopagus conjoined twins.

PMID- 29634557
TI  - Postdural Puncture Headache Treated With Epidural Blood Patch and Subsequent
      Resolution of Atypical Odontalgia: A Case Report.
AB  - A 37-year-old gravida 5 para 4 with gestational hypertension underwent uneventful
      repeat cesarean delivery and tubal ligation under combined spinal-epidural
      anesthesia. On postoperative day 3, she developed a postural headache, unrelieved
      by caffeine, ibuprofen, and hydration. On postoperative day 8, she returned to
      the hospital for treatment. An epidural blood patch was administered, providing
      immediate and complete relief of her headache and bilateral upper and lower
      dental pain, which she noted arising concomitantly with her headache. We suspect
      bilateral traction on cranial nerve V2 and V3, secondary to intracranial
      hypotension after dural puncture, as the cause of her pain.

PMID- 29634558
TI  - Successful Treatment of Refractory Cardiac Arrest With beta-Blockade and
      Extracorporeal Life Support in a Pediatric Patient With Catecholaminergic
      Polymorphic Ventricular Tachycardia: A Case Report.
AB  - We describe a case of refractory pulseless polymorphic ventricular tachycardia
      successfully treated with a bolus of propranolol intravenously, followed by an
      esmolol infusion and extracorporeal life support for 4 days in a 12-year-old boy
      later diagnosed with catecholaminergic polymorphic ventricular tachycardia. He
      had an excellent neurological outcome. Genetic testing for mutations associated
      with cardiac arrhythmias yielded a mutation of the syntrophin alpha-1 gene. The
      pathogenicity of this specific variant is uncertain. A mutation of this gene at a
      different locus is implicated in rare cases of long-QT syndrome. The patient
      subsequently underwent left cardiac sympathetic denervation followed by
      implantable cardiac defibrillator insertion. He remains symptom and arrhythmia
      free on atenolol.

PMID- 29634559
TI  - Perioperative Management of a Child With Glucose Transporter Type 1 Deficiency
      Syndrome: A Case Report.
AB  - Glucose transporter type 1 deficiency syndrome (GLUT1DS) causes central nervous
      system dysfunction including intractable epilepsy caused by impaired glucose
      transport to the brain. To prevent convulsions and maintain an energy source for
      the brain in patients with GLUT1DS, the maintenance of adequate ketone body
      concentrations, compensation of metabolic acidosis, and reduction of surgical
      stress are essential. We here report the perioperative management of a child with
      GLUT1DS.

PMID- 29634560
TI  - Sphenopalatine Ganglion Block Successfully Treats Migraines in a Type 1 Arnold
      Chiari Malformation Pregnant Patient: A Case Report.
AB  - A 32-year-old woman at 36 weeks gestation with a medical history of corrected
      Type 1 Arnold Chiari malformation presented with an intractable headache. When
      methylprednisolone and morphine treatment provided no relief, we performed 2
      topical transnasal sphenopalatine ganglion blocks by applying 4% lidocaine drops
      into each nostril via a cotton-tipped applicator. The patient's symptoms
      significantly improved, and she was discharged home the same day. She has been
      without relapse of headaches during the 6 months of follow-up by our pain
      service.

PMID- 29634561
TI  - Axillary Artery Dissection After Ultrasound-Guided Infraclavicular Brachial
      Plexus Block: A Case Report.
AB  - A 52-year-old man with end-stage renal disease underwent ultrasound-guided
      infraclavicular brachial plexus block for revision of an arteriovenous fistula.
      On postoperative day 2, the patient developed pain and loss of motor function in
      the surgical extremity. A computed tomography angiogram revealed complete
      dissection of the axillary artery. The dissection was emergently treated with a
      bypass graft, resulting in complete resolution of paralysis and pain. Sensory
      deficits resolved over the next 3 days. Smoking, hypertension, diabetes mellitus,
      and chronic intake of a calcineurin inhibitor might have predisposed the patient
      to iatrogenic arterial dissection.

PMID- 29634562
TI  - Novel Association of Juvenile Polyposis Syndrome With Atrial Septal Aneurysm and
      Patent Foramen Ovale: A Case Report.
AB  - Juvenile polyposis syndrome is an autosomal-dominant disorder characterized by
      the presence of hundreds of gastrointestinal polyps. The genes most commonly
      found are BMPR1A and SMAD4. The latter has been linked to vascular malformations
      and hereditary hemorrhagic telangiectasias. We present the case of a young woman
      diagnosed with juvenile polyposis syndrome and SMAD-4 mutation, who developed
      embolic strokes from an atrial septal aneurysm and patent foramen ovale. This
      case highlights the propensity of patients with juvenile polyposis syndrome and
      SMAD-4 mutations to develop atrial septal aneurysm and patent foramen ovale, and
      warrants appropriate cardiac workup in at-risk individuals.

PMID- 29634563
TI  - Atrioventricular Disruption After Aortic Valve Surgery: Early Detection by
      Intraoperative Echocardiography: A Case Report.
AB  - Atrioventricular groove separation is a rare complication of mitral valve
      surgery. We present a case occurring during aortic valve surgery that was
      detected by the anesthesiologist using transesophageal echocardiography (TEE).
      During weaning from cardiopulmonary bypass after uneventful replacement of a
      severely calcified aortic valve, blood flow was seen on TEE leaving the left
      ventricular outflow tract just below the annulus of the aortic valve. This blood
      flow expanded into the aorto-mitral curtain during systole, consistent with
      atrioventricular groove separation. We review the pathophysiology behind groove
      separations and discuss diagnosis of these rare conditions using TEE.

PMID- 29634564
TI  - Benefits of Ultrasound Imaging for Placement of Caudal Epidural Blockade in 3
      Pediatric Patients: A Case Report.
AB  - Pediatric caudal epidural blockade, the most common pediatric regional
      anesthetic, is classically placed using surface landmark technique with
      infrequent use of ultrasound guidance. We present 3 cases where ultrasound
      guidance facilitated successful placement and helped prevent complications. One
      infant had an unanticipated S5 dural sac necessitating needle redirection to
      avoid subarachnoid injection. A 5-year old had proper needle position with
      inability to inject secondary to needle blockage confirmed with ultrasound. An
      expremature infant had initial needle placement anterior to the sacrum with
      subsequent proper placement using real-time ultrasound imaging. Ultrasound
      guidance for pediatric caudal placement confers advantages and increased routine
      use should be considered.

PMID- 29634565
TI  - Postoperative Hearing Loss in a Patient With Crouzon Syndrome: A Case Report.
AB  - Sudden postoperative hearing loss is rare, and thought to be caused by a variety
      of mechanisms. Here we report on a patient with Crouzon syndrome who experienced
      multiple episodes of postoperative hearing loss, with persistent hearing loss
      occurring after she received nitrous oxide as part of a general anesthetic.
      Nitrous oxide is known to cause pressure changes in closed air spaces. Patients
      with craniofacial syndromes may have acoustic nerve compression from skull base
      and cartilage anomalies that cause narrowing of the internal acoustic meatus.
      These anatomic variations may make patients more susceptible to increased middle
      ear pressure secondary to nitrous oxide, increasing their risk for hearing loss.

PMID- 29634566
TI  - Thromboelastography Before Epidural Placement in a Thrombocytopenic Parturient
      With Gaucher Disease Treated With Imiglucerase: A Case Report.
AB  - Gaucher disease is a common inborn error of metabolism leading to widespread
      chronic inflammation and often thrombocytopenia. Here we discuss assessment of
      coagulation in a parturient with Gaucher disease treated with imiglucerase, who
      presented with thrombocytopenia and requested epidural analgesia for planned
      vaginal delivery. We used thromboelastography to determine the safety of placing
      an epidural catheter and to plan for potential peripartum bleeding. The patient
      had a normal coagulation profile by thromboelastography and had uncomplicated
      epidural analgesia for a successful spontaneous vaginal delivery.

PMID- 29634567
TI  - Successful Management of a Patient With X-Linked Myotubular Myopathy for
      Scoliosis Surgery and Previous Cardiac Arrest After Prone Positioning: A Case
      Report.
AB  - A 15-year-old boy with X-linked myotubular myopathy associated with severe
      hypotonia and pectus excavatum presented for posterior spinal fusion of T2-sacrum
      because of rest pain and severe progressive neuromuscular scoliosis. Previously,
      he experienced 2 separate instances of cardiac arrest after prone positioning
      under general anesthesia. A preoperative computed topography angiogram in the
      supine and prone positions revealed inferior vena cava and right ventricular
      outflow tract obstruction on prone positioning. Successful positioning and
      posterior spinal fusion occurred by staging the procedure, correction of volume
      status, early use of vasoactive and inotropic agents, and oblique prone
      positioning.

PMID- 29634568
TI  - Rigid Esophagoscopy-Induced Aortic Rupture During Oral Gastric Tube Placement in
      Patient With Esophageal Stricture: A Case Report.
AB  - This is the first account of significant aortic injury during diagnostic rigid
      esophagoscopy in an adult with an esophageal stricture. We describe the resultant
      hemothorax and hemodynamic collapse and the successful treatment with massive
      volume resuscitation, vasopressors, and timely surgical intervention including
      thoracic endovascular aortic repair. We discuss the importance of rapid
      diagnosis, relevant anatomy, treatment modalities, and communication as
      cornerstones for learning.

PMID- 29634569
TI  - Spinal Cord Stimulation Treatment for Chronic Right Subcostal Neuralgia Secondary
      to Laparoscopic Cholecystectomy: A Case Report.
AB  - The use of spinal cord stimulator (SCS) treatment has been particularly effective
      as an adjunct in treating mixed neuropathic, nociceptive, and radicular pain
      conditions. There are no published studies on the use of SCS for chronic pain
      syndrome after laparoscopic cholecystectomy. We successfully used an SCS on a 31
      year-old woman with a 4-year history of intractable right-sided subcostal pain
      after laparoscopic cholecystectomy. This case provides strong evidence that SCS
      should be considered as a treatment option for chronic postsurgical pain after
      laparoscopic cholecystectomy not amenable to standard therapies.

PMID- 29634570
TI  - Use of Laryngeal Mask Airway to Preoxygenate and Ventilate Through a Laryngeal
      Stoma in a Patient Undergoing General Anesthesia: A Case Report.
AB  - The use of the laryngeal mask airways is well established in routine and
      emergency airway management. Due to its traditional use as a supraglottic airway,
      it is often overlooked in patients with abnormal airway anatomy such as
      tracheostomies and laryngeal stomas. We present the unique method of using the
      laryngeal mask airways externally to facilitate preoxygenation and ventilation in
      a patient with a laryngeal stoma.

PMID- 29634571
TI  - Paraplegia After Laparotomy for Large Bowel Obstruction: A Case Report.
AB  - We report persistent postoperative paraplegia on recovery from anesthesia after
      emergent exploratory laparotomy for large bowel obstruction in a cachectic
      patient with an abdominal aortic aneurysm. Postoperative cervical, thoracic, and
      lumbar spine magnetic resonance imaging revealed only cervical spinal stenosis.
      We hypothesize that intraoperative embolization possibly caused by manipulation
      of an atherosclerotic aorta, and a brief episode of intraoperative hypotension
      resulted in spinal cord ischemia. This report highlights the importance of
      maintaining intraoperative hemodynamic stability and careful handling of the
      abdominal aorta, especially in underweight patients with an abdominal aortic
      aneurysm.

PMID- 29634572
TI  - T1 Paravertebral Catheter for Postoperative Pain Management After First Rib
      Resection for Venous Thoracic Outlet Syndrome: A Case Report.
AB  - While it has been shown that a paravertebral block provides effective
      postoperative analgesia for patients undergoing thoracic surgeries, including
      first rib resection, this is the first reported case of a paravertebral catheter
      used for perioperative analgesia in a patient undergoing first rib resection. We
      present the case of a 76-year-old woman with right upper extremity swelling who
      underwent infraclavicular first rib resection for venous thoracic outlet
      syndrome. Continuous infusion of ropivacaine through a T1 paravertebral catheter,
      which was placed before induction of general anesthesia but after T1 and T2
      paravertebral blocks, provided effective postoperative pain control. Our
      experience suggests that paravertebral catheter infusions of local anesthetics
      may be effective adjuncts to general anesthesia in patients undergoing first rib
      resection and warrants further investigation.

PMID- 29634573
TI  - Successful Primary Percutaneous Coronary Intervention for Acute Myocardial
      Infarction During Resuscitation From Cardiac Arrest by Combined Mechanical Chest
      Compressions and Intra-aortic Balloon Pump Counterpulsation: A Case Report.
AB  - Prolonged cardiac arrest (CA) in patients with acute myocardial infarction can be
      associated with poor prognosis. Successful revascularization with primary
      percutaneous coronary intervention (pPCI) remains the reference therapy for these
      patients. However, performing a pPCI during CA is challenging and the use of
      automatic chest compression devices or mechanical support systems might be
      warranted to facilitate the pPCI procedure and achieve good outcomes. We present
      a patient with inferior myocardial infarction and cardiogenic shock, followed by
      refractory CA who underwent successful pPCI with a novel approach integrating the
      simultaneous use of an automated chest compression system and intra-aortic
      balloon pump counterpulsation.

PMID- 29634574
TI  - Airway Management Approach in Nasocutaneous Fistula: A Case Report.
AB  - We present a case of a 63-year-old man with nasocutaneous fistula located outside
      the area covered by a large adult facemask. The patient was uncooperative for the
      standard airway assessment and any attempt at awake intubation. Positive pressure
      ventilation was compromised by the fistula. Although the incidence of overall
      complications, including fistula formation, following free flap reconstruction
      for oropharyngeal cancer is reported as high as 20%, few case reports detailing
      airway management exist. We demonstrate that it is possible to use conventional
      techniques to induce and ventilate a patient with a large, externalized, airway
      fistula by covering the defect with an occlusive transparent dressing.

PMID- 29634575
TI  - Conservative Management of Neuropathic Pain in a Patient With Pancoast-Tobias
      Syndrome: A Case Report.
AB  - Pancoast-Tobias syndrome characterizes the signs and symptoms of a superior
      pulmonary sulcus tumor, and includes arm and shoulder pain, atrophy of intrinsic
      hand muscles, and ipsilateral Horner syndrome. The rarity and overall poor
      prognosis of patients with superior pulmonary sulcus tumors associated with
      Pancoast-Tobias syndrome has led to few reports detailing pain management
      strategies with adjunctive therapies, such as continuous infusions of ketamine
      and lidocaine, chemotherapy, radiation, and multimodal oral medication regimens.
      This case highlights the diagnosis and treatment of pain in a patient with
      Pancoast-Tobias syndrome.

PMID- 29634576
TI  - Transcutaneous Electrical Nerve Stimulation in Treatment of Occipital Neuralgia:
      A Case Report.
AB  - Occipital neuralgia is the third most common headache syndrome after migraine and
      tension type headaches. There is no well-established treatment regimen for a
      reliable cure. The current case presents a 39-year-old woman, diagnosed with
      occipital neuralgia of idiopathic cause. The condition was difficult to control
      by conservative or interventional approaches. The patient was started on
      conventional transcutaneous electrical nerve stimulation, 3 sessions per week.
      After the procedure, the patient achieved significant pain relief: 1-2/10 on the
      numeric rating scale, pain initially being 10/10. With maintenance therapy
      consisting of physical therapy, deep tissue massage, and muscle relaxants, 12
      months after starting transcutaneous electrical nerve stimulation therapy, she is
      pain free.

PMID- 29634577
TI  - Evaluation of ground glass nodules.
AB  - PURPOSE OF REVIEW: Ground glass nodules (GGNs) represent an indolent subset of
      lung nodules including preinvasive nonsmall-cell lung cancer associated with a
      favorable prognosis and low risk for progression. Increased performance of
      screening cat-scan (CT) for high-risk patients has identified an increasing
      number of GGNs. The management of these nodules is founded mostly on single
      institution data and currently no universally accepted recommendations help guide
      clinicians managing these patients. RECENT FINDINGS: The solid component within a
      GGN is the key determinant of prognosis and is best defined by evaluating nodule
      density on mediastinal windows of a chest CT. When a GGN is small (<3 cm),
      associated with minimal change in size (<25% growth per year), and there is no
      demonstration of a significant solid component on mediastinal windows (<2 mm in
      diameter), patients can be safely observed with serially imaging. These imaging
      features also help distinguish patients that may harbor early-stage lung cancers
      that benefit from local treatment options. SUMMARY: The majority of GGNs do not
      undergo significant progression during surveillance. Evidence of nodule
      progression on interval imaging may be a trigger for consideration of a local
      treatment option such as surgical resection. Large prospective studies are needed
      in the United States to validate the more robust data derived from Asian studies
      to help formulate formal recommendations for surveillance and treatment. Future
      improvements in imaging and the molecular characterization of these GGNs may
      further refine which patients are at risk for progression.

PMID- 29634578
TI  - Effects of an Interdisciplinary Practice Bundle for Second-Stage Labor on
      Clinical Outcomes.
AB  - BACKGROUND: There is renewed interest in second-stage labor practices as recent
      evidence has challenged historical perspectives on safe duration of second-stage
      labor. Traditional practices and routine interventions during second-stage have
      uncertain benefit for low-risk women and may result in cesarean birth. PURPOSE:
      The purpose of this quality improvement project was to implement an
      interdisciplinary second-stage practice bundle to promote safe outcomes including
      method of birth and women's birth experience. METHODS: Standardized second-stage
      labor evidence-based practice recommendations structured into a 5 Ps practice
      bundle (patience, positioning, physiologic resuscitation, progress, preventing
      urinary harm) were implemented across 34 birthing hospitals in the Trinity Health
      system. RESULTS: Significant improvements were observed in second-stage
      practices. Association of Women's Health, Obstetric and Neonatal Nurses'
      perinatal nursing care quality measure Second-Stage of Labor: Mother-Initiated
      Spontaneous Pushing significantly improved [pre-implementation 43% (510/1,195),
      post-implementation 76% (1,541/2,028), p < .0001]. Joint Commission Perinatal
      Care-02: nulliparous, term, singleton, vertex cesarean rate significantly
      decreased (p = 0.02) with no differences in maternal morbidity, or negative
      newborn birth outcomes. Unexpected complications in term births significantly
      decreased in all newborns (p < 0.001), and for newborns from vaginal births (p =
      0.03). Birth experience satisfaction rose from the 69th to the 81st percentile.
      CLINICAL IMPLICATIONS: Implementing 13 evidence-based second-stage labor
      practices derived from the Association of Women's Health, Obstetric and Neonatal
      Nurses and the American College of Nurse-Midwives professional guidelines
      achieved our goals of safely reducing primary cesarean birth among low-risk
      nulliparous women, and optimizing maternal and fetal outcomes associated with
      labor and birth. By minimizing routine interventions, nurses support physiologic
      birth and improve women's birth satisfaction.

PMID- 29634580
TI  - Complementary medicine for axial spondyloarthritis: is there any scientific
      evidence?
AB  - PURPOSE OF REVIEW: Majority of patients with axial spondyloarthritis (axSpA)
      report use of complementary and alternative medicine (CAM) therapies before and
      even after the diagnosis, due to perceived efficacy and wide-spread belief that
      these modalities lack side effects. In this review, we describe the available
      scientific evidence for the CAM therapies in axSpA. RECENT FINDINGS: Clinical
      trials of the CAM therapies in axSpA are generally hampered by small sample size,
      short duration, difficulties in blinding, lack of control groups and strong
      placebo effect. Nonetheless, exercise programs like Pilates and mind-body
      techniques such as Tai Chi may have favorable effect on the disease activity and
      function. Although not yet confirmed, the modulation of the microbiome with the
      help of probiotics or fecal transplant has face validity given the evolving
      scientific rationale. Diet has only limited role in the management of axSpA. Deep
      tissue massage, omega-3 fatty acids and Stanger bath were found to be useful in
      small studies. CAM therapies are not always entirely well tolerated, particularly
      the manipulative techniques like chiropractic and Tui-na in patients with
      advanced disease and osteoporosis. There are no trials of yoga in axSpA despite
      the wider acceptance and use of yoga as an effective mind-body technique.
      SUMMARY: Larger and better quality clinical trials of CAM therapies are needed to
      confirm their efficacy and safety in the management of axSpA and to include them
      in the 'mainstream' medicine.

PMID- 29634579
TI  - Synergistic inhibitory effect of capsaicin and dihydrocapsaicin on in-vitro
      platelet aggregation and thromboxane formation.
AB  - : Capsaicinoids, including capsaicin (CAP) and dihydrocapsaicin (DHC), the
      pungent principles of pepper fruits, individually inhibit in-vitro platelet
      aggregation. However, their effects, when present together, are not known. The
      aims of this study were to compare the effects of CAP and DHC alone, and in
      combination in the ratio that they are found in chilies (~60% CAP : 40% DHC), on
      in-vitro platelet aggregation, platelet count and thromboxane B2 (TXB2)
      formation. The effects of 12.5 and 6.25 MUmol/l CAP and DHC individually, and in
      combination (CAP : DHC, 60 : 40) on arachidonic acid-induced, ADP-induced and
      collagen-induced aggregation, were investigated. Platelet count was determined
      preincubation and postincubation with CAP and DHC and in combination. TXB2
      formation from platelets treated with arachidonic acid in the absence and
      presence of CAP and DHC individually, and in combination, was measured. Compared
      with control, CAP and DHC (12.5 MUmol/l) inhibited arachidonic acid-induced
      aggregation by 23.2 and 25.3%, respectively (both P < 0.01). In combination, CAP
      and DHC exhibited further inhibition in arachidonic acid-induced aggregation (CAP
      : DHC, 3.75 : 2.5 MUmol/l, 36.5%, P = 0.01; 7.5 : 5 MUmol/l, 57.5%, P < 0.001),
      compared with control. Incubation of platelets with caspaicinoids did not
      significantly affect the platelet count. In addition, the CAP : DHC (7.5 : 5
      MUmol/l) combination significantly inhibited (P < 0.001) TXB2 formation, compared
      with the individual capsaicinoids. Capsaicinoids had no effect ADP-induced or
      collagen-induced aggregation. The combination of CAP and DHC produces a
      significantly greater inhibitory effect on arachidonic acid-induced platelet
      aggregation and subsequent TXB2 formation, compared with the individual
      capsaicinoids.

PMID- 29634581
TI  - Fracture prediction and prevention: will newer technologies help?

PMID- 29634582
TI  - Infections and autoimmunity -new insights into an age-old reciprocity.

PMID- 29634583
TI  - Restless Genital Syndrome Induced by Milnacipran.
AB  - OBJECTIVES: Restless genital syndrome (RGS) includes discomfort, pain, numbness,
      vibration, restlessness, or a burning sensation involving the vagina, perineum,
      pelvis, penis, and proximal portion of the lower limbs in patients. The RGS has
      been sometimes reported in Parkinson disease. In patients without Parkinson
      disease, RGS is also known as persistent genital arousal disorder (PSAS), which
      includes uncontrollable genital arousal, with or without orgasm or genital
      engorgement, unrelated to sexual desire. Although withdrawal from selective
      serotonin reuptake inhibitors antidepressants is reported to induce PSAS, there
      is no report of RGS or PSAS induced by antidepressants. METHODS: We obtained the
      consent for the presentation and have not identified individuals for ethical
      reasons. RESULTS: We first report a woman patient with depression induced RGS by
      milnacipran (MLN). CONCLUSIONS: We discuss the relationship with restless legs
      syndrome and the difference from akathisia. It is highly possible MLN affected
      her RGS because she experienced RGS for the first time after the dose of MLN was
      increased. A limitation of this report is that we stopped MLN and administered
      gabapentin enacarbil immediately. We should join MLN to the list of compounds
      suspected of inducing RGS.

PMID- 29634584
TI  - Trazodone and Parkinsonism: The Link Strengthens.
AB  - Trazodone, the most sedating atypical antidepressant, is widely used as an off
      label hypnotic especially in the elderly. Although generally considered safe, it
      can potentially inhibit midbrain dopaminergic neurotransmission leading to the
      emergence of extrapyramidal adverse effects. Two previous cases of trazodone
      induced parkinsonism have been described after its prolonged use as an
      antidepressant; however, there is no published case of secondary parkinsonism
      caused by trazodone in a nondepressed person after its use as a hypnotic. Here,
      we present a case of rapid development of bradykinetic-rigid parkinsonism
      temporally linked to the use of trazodone as a hypnotic in a nondepressed elderly
      man. Because of lack of awareness, this potential association was missed by his
      primary care physician and general neurologist. He was diagnosed as having
      idiopathic parkinsonism (Parkinson disease) and referred to a movement disorder
      neurologist. A secondary cause was suspected by his movement disorder neurologist
      that led to rapid withdrawal of trazodone and complete reversal of his symptoms.
      A practice point that needs to be underscored is that trazodone's use as a
      hypnotic can cause parkinsonism. All health care providers should be aware of
      this serious but seemingly fully reversible potential adverse effect.

PMID- 29634586
TI  - Transgenerational consequences of prepregnancy chronic morphine use on spatial
      learning and hippocampal Mecp2 and Hdac2 expression.
AB  - There has recently been increasing interest in the transgenerational effects of
      opioids. Herein, transgenerational consequences of maternal chronic morphine
      consumption before gestation were investigated at the behavioral and molecular
      levels of next two generations. Twelve female Wistar rats were randomly divided
      into two groups: pregestation morphine-consuming and control mothers. Morphine
      consuming mothers had access to morphine solution ad libitum for 2 months,
      whereas the control mothers received only tap water. One month after stopping
      morphine consumption, rats were mated. After parturition, male and female
      offspring and later grandoffspring of morphine-consuming and control mothers were
      divided and used as the study groups. Behavioral testing comprised spatial memory
      assessment using Morris water maze. Hippocampal expressions of Mecp2 and Hdac2
      were investigated through real-time PCR. Spatial memory was significantly
      diminished in male but not female offspring and grandoffspring of morphine
      consuming mothers versus control (P<0.01). Hippocampal Mecp2 and Hdac2 were
      significantly upregulated in male but not in female offspring and grandoffspring
      of morphine-consuming mothers compared with control (P<0.05). Consequences of
      prepregnancy morphine consumption have sex differences and are detectable at the
      behavioral and molecular level over at least the next two generations.

PMID- 29634585
TI  - Altered whole-brain gray matter volume in high myopia patients: a voxel-based
      morphometry study.
AB  - High myopia (HM) was associated with impaired long-distance vision. Previous
      neuroimaging studies showed that abnormal visual experience leads to dysfunction
      in brain activity in HM even corrected. However, whether alterations in brain
      structure occur in HM remains unknown. In this study, we analyzed the difference
      in the whole-brain gray matter volume (GMV) and white matter volume between HM
      patients and healthy controls (HCs) using a voxel-based morphology method. A
      total of 82 HM patients (52 men and 30 women) and 58 HCs (28 men and 30 women),
      matched closely in terms of age and education, were enrolled in this study. All
      participants underwent MRI scans. The MRI data were processed using the SPM8
      software. The relationship between the mean GMV values of the brain regions and
      clinical features, including refractive diopter and the mean retinal nerve fiber
      layer thickness, in the HM group were analyzed using Pearson's correlation.
      Compared with HCs, HM patients showed significantly decreased GMV values in the
      right cuneus/lingual gyrus and the right thalamus. In contrast, HM groups showed
      higher GMV values in the brain stem, right parahippocampal gyrus/thalamus, left
      parahippocampal gyrus/thalamus, as well as the right and the left putamen. No
      significantly different white matter volume values were found between the two
      groups. Moreover, in the HM group, the mean retinal nerve fiber layer of the left
      eye showed a negative correlation with the mean GMV values of the brain stem (r=
      0.218; P=0.049), right parahippocampal gyrus/thalamus (r=-0.262; P=0.017), left
      parahippocampal gyrus/thalamus (r=-0.249; P=0.024), and left putamen (r=-0.232;
      P=0.036). We found that HM patients showed an altered brain structure in the
      visual pathway regions and the limbic system, which may provide useful
      information to explore the neural mechanisms of impaired long-distance vision in
      HM.

PMID- 29634587
TI  - Exposure to bisphenol A affects GABAergic neuron differentiation in neurosphere
      cultures.
AB  - Endocrine-disrupting chemicals (EDCs) influence not only endocrine functions but
      also neuronal development and functions. In-vivo studies have suggested the
      relationship of EDC-induced neurobehavioral disorders with dysfunctions of
      neurotransmitter mechanisms including gamma-aminobutyric acid (GABA)ergic
      mechanisms. However, whether EDCs affect GABAergic neuron differentiation remains
      unclear. In the present study, we show that a representative EDC, bisphenol A
      (BPA), affects GABAergic neuron differentiation. Cortical neurospheres prepared
      from embryonic mice were exposed to BPA for 7 days, and then neuronal
      differentiation was induced. We found that BPA exposure resulted in a decrease in
      the ratio of GABAergic neurons to total neurons. However, the same exposure
      stimulated the differentiation of neurons expressing calbindin, a calcium-binding
      protein observed in a subpopulation of GABAergic neurons. These findings
      suggested that BPA might influence the formation of an inhibitory neuronal
      network in developing cerebral cortex involved in the occurrence of
      neurobehavioral disorders.

PMID- 29634588
TI  - Arthroscopic Treatment of Labral Tears: A Critical Analysis Review.

PMID- 29634589
TI  - Psychometric Properties of Patient-Reported Outcome Measures for Use in Patients
      with Anterior Cruciate Ligament Injuries: A Systematic Review.
AB  - BACKGROUND: Despite the high costs of anterior cruciate ligament (ACL) injuries
      to patients and society, we are not aware of any systematic reviews that have
      been performed on patient-reported outcome instruments designed for this patient
      population. The purpose of the present review is to identify currently available
      patient-reported outcome questionnaires for patients with ACL injuries, to
      appraise and assess the methodological quality and psychometric evidence of the
      evaluations of identified instruments, and to summarize the overall evidence for
      each included questionnaire. METHODS: A computerized literature search was
      performed to identify articles appropriate for inclusion in this systematic
      review. Search terms were related to outcome instruments, ACL injuries, and
      psychometric properties. Two independent reviewers assessed the suitability of
      articles for inclusion. The methodological quality of instrument evaluation was
      assessed with use of the Consensus-based Standards for the Selection of Health
      Status Measurement Instruments (COSMIN) checklist. Psychometric properties were
      assessed with use of the quality criteria established by Terwee et al. The 2
      assessments were synthesized to obtain an overall rating of the psychometric
      evidence for each questionnaire. RESULTS: Forty-one studies investigating 24
      instruments were included. The International Knee Documentation Committee (IKDC)
      Form and the Knee injury and Osteoarthritis Outcome Score (KOOS) were the most
      frequently assessed instruments. The ACL-Return to Sport after Injury (ACL-RSI)
      scale had 6 properties with positive evidence and was the highest-quality
      instrument overall. CONCLUSIONS: Many of the included studies had low COSMIN
      ratings. The ACL-RSI is a reliable and valid scale to measure outcomes for
      patients with ACL injuries. Further assessments with improved methodological
      quality are needed to determine the psychometric properties of other instruments.

PMID- 29634590
TI  - Cemented Compared with Uncemented Femoral Fixation in the Arthroplasty Treatment
      of Displaced Femoral Neck Fractures: A Critical Analysis Review.

PMID- 29634591
TI  - Herpesvirus Infection in Infants with Gastroschisis.
AB  - BACKGROUND: Gastroschisis is a congenital malformation that has been shown to be
      more common in younger mothers and appears to be increasing in prevalence in the
      United States and elsewhere. Epidemiologic data suggest a potential role of
      infection and recent studies report an association between maternal antibodies to
      human herpesviruses (HHV) and development of gastroschisis. METHODS: In this
      study, we examined newborn bloodspots from 50 children with gastroschisis and 50
      healthy controls using a highly sensitive digital droplet polymerase chain
      reaction assay covering eight human herpesviruses [herpes simplex sirus 1/2,
      Epstein-Barr virus (HHV-4), cytomegalovirus (HHV-5), HHV-6A/B, HHV-7, and HHV-8],
      to examine the presence of herpesvirus DNA at birth, which would suggest in utero
      infection. RESULTS: One control tested positive for low-level cytomegalovirus
      infection. We found no evidence of an association between herpesvirus DNA in
      neonatal blood spots taken at birth and gastroschisis. CONCLUSIONS: Our results
      do not support direct involvement of herpesviruses in the etiology of
      gastroschisis. However, there are several limitations in our study, most notably
      the known induction of this congenital malformation early in pregnancy and our
      analysis of blood taken at birth. Therefore, we cannot conclude that
      herpesviruses play no role in the etiology of gastroschisis and further research
      is needed to better define this relationship.

PMID- 29634592
TI  - Associations Between Childhood Thyroid Cancer and External Radiation Dose After
      the Fukushima Daiichi Nuclear Power Plant Accident.

PMID- 29634593
TI  - Oral Care Clinical Trial to Reduce Non-Intensive Care Unit, Hospital-Acquired
      Pneumonia: Lessons for Future Research.
AB  - Hospital-acquired pneumonia (HAP) contributes greatly to patient mortality and
      healthcare costs. Studies have shown that aggressive oral care in intensive care
      units (ICUs) can significantly reduce pneumonia rates, and hospitals have
      implemented stringent protocols in this setting. However, little is known about
      the effectiveness of aggressive oral care in reducing HAP in non-intensive care
      wards, prompting us to conduct a nonrandomized controlled clinical trial. A
      structured toothbrushing program was provided to an experimental cohort of
      patients. A control group received usual care. Patient demographics,
      toothbrushing frequency, and pneumonia diagnosis were recorded over a 3.5-month
      period. Difference in pneumonia rates was computed using unadjusted and
      multivariate logistic regression analyses. No significant difference in pneumonia
      rates between control and experimental groups was found (1.7% versus 1.8%).
      Toothbrushing rates increased significantly in the experimental group (p = .002)
      but fell short of protocol frequency. It became apparent that aggressive
      toothbrushing program implementation requires nursing-led interdisciplinary
      involvement, more intensive training, a streamlined documentation system, and
      efficient compliance tracking. Lessons from this study should be used for future
      large-scale research. A secondary analysis of these data did, however, suggests
      that increasing toothbrushing rates may have the potential to reduce pneumonia in
      the non-ICU acute care setting.

PMID- 29634594
TI  - Pilot Teledermatology Service for Assessing Solitary Skin Lesions in a Tertiary
      London Dermatology Center.
AB  - BACKGROUND: Efficient clinical pathways are needed to meet the growing pressures
      in dermatology due to the significant rise in the number of suspected skin cancer
      referrals. Our hospital serves a wide geographical area and receives a large
      number of 2-week-wait (2WW) suspected skin cancer referrals. In the United
      Kingdom, approximately 10-12% of 2WW referrals are diagnosed as skin cancers
      fulfilling the 2WW criteria. PURPOSE: We sought to assess the role of
      teledermatology in reducing hospital consultations for patients referred via the
      dermatology 2WW pathway. METHODS: We piloted a teledermatology service and
      detailed the clinical outcomes of patients with solitary skin lesions of
      uncertain diagnosis triaged through this pathway. Seventy-six primary care
      referrals were reviewed by consultant dermatologists and analyzed against the
      British Association of Dermatologists' teledermatology audit standards. RESULTS:
      In 52/76 (68%) of patients, confident benign diagnoses were made, avoiding the
      need for a face-to-face (FTF) consultation. CONCLUSIONS: Our results showed that
      with adequate image quality, teledermatology can be used to accurately diagnose
      skin lesions. IMPLICATIONS: Teledermatology can significantly reduce the number
      of urgent referrals necessitating FTF appointments, therefore providing a new
      solution to streamline care delivery.

PMID- 29634595
TI  - Chronic subdural hematoma: A common complexity.

PMID- 29634596
TI  - Disease-modifying treatments for early and advanced multiple sclerosis: a new
      treatment paradigm.
AB  - PURPOSE OF REVIEW: The treatment of multiple sclerosis is evolving rapidly with
      11 classes of disease-modifying therapies (DMTs). This article provides an
      overview of a new classification system for DMTs and treatment paradigm for using
      these DMTs effectively and safely. RECENT FINDINGS: A summary of research into
      the use of more active approaches to early and effective treatment of multiple
      sclerosis with defined treatment targets of no evident disease activity (NEDA).
      New insights are discussed that is allowing the field to begin to tackle more
      advanced multiple sclerosis, including people with multiple sclerosis using
      wheelchairs. However, the need to modify expectations of what can be achieved in
      more advanced multiple sclerosis are discussed; in particular, the focus on
      neuronal systems with reserve capacity, for example, upper limb, bulbar and
      visual function. SUMMARY: The review describes a new more active way of managing
      multiple sclerosis and concludes with a call to action in solving the problem of
      slow adoption of innovations and the global problem of untreated, or
      undertreated, multiple sclerosis.

PMID- 29634597
TI  - Identifying and targeting patients with predicted 30-day hospital readmissions
      using the revised LACE index score and early postdischarge intervention.
AB  - AIMS: Reducing potentially avoidable hospital readmissions has been the target of
      several healthcare initiatives, including the readmission prevention team (RAPT)
      at Western Health, Melbourne. Study aims were to evaluate if the revised LACE
      (length of stay, acuity of admission, Charlson Comorbidity Index, emergency
      department visits in the past 6 months) index would identify high risk of early
      readmission (<=30 days postdischarge), and if postdischarge clinic and community
      services follow-up would reduce readmission rate. METHODS: A prospective study
      was conducted among all general medicine inpatients within a tertiary hospital in
      Melbourne, Australia between February to April 2016, with risk screening using
      the revised LACE index, alongside abbreviated mental test and clinical frailty
      scale testing, with high-risk patients (revised LACE >= 8) offered specialist
      clinic appointment and/or referral to community services. RESULTS: Among 781
      patients (873 admission episodes), 358 (41.0%) admission episodes were classified
      as high risk of early readmission. Revised LACE index scores were equivalent for
      readmission vs. non-readmission episodes, {median 7 [interquartile range (IQR) 5,
      8] vs. 7 [IQR 4, 8])}, as were median abbreviated mental test (8 [IQR 6, 9] vs. 8
      [IQR 6, 9]) and clinical frailty scale scores (5 [IQR 3, 6] vs. 5 [IQR 3, 6]).
      Early readmission rates were equivalent for those who received compared with did
      not receive RAPT intervention (14.3 vs. 14.7%), albeit confounded by lack of
      identification of readmission risk using the revised LACE index. A total of 53
      (14.8%) of the 358 high-risk admission episodes formally declined RAPT follow-up.
      CONCLUSION: This study highlighted the complexities of addressing hospital
      readmissions, with challenges in identifying those at risk, and low uptake and
      impact of current intervention strategies. Future research directions may
      evaluate other contributors to readmission risk, and the development of
      acceptable postdischarge interventions to effectively address risk.

PMID- 29634598
TI  - A Web of Complexity: Untangling the Routes of Rectal Chlamydia Acquisition.

PMID- 29634599
TI  - Comparison of Algorithms to Triage Patients to Express Care in a Sexually
      Transmitted Disease Clinic.
AB  - BACKGROUND: The ideal approach to triaging sexually transmitted disease (STD)
      clinic patients between testing-only express visits and standard visits with
      clinician evaluation is uncertain. METHODS: In this cross-sectional study, we
      used classification and regression tree analysis to develop and validate the
      optimal algorithm for predicting which patients need a standard visit with
      clinician assessment (i.e., to maximize correct triage). Using electronic medical
      record data, we defined patients as needing a standard visit if they reported STD
      symptoms, received any empiric treatment, or were diagnosed as having an
      infection or syndrome at the same visit. We considered 11 potential predictors
      for requiring medical evaluation collected via computer-assisted self-interview
      when constructing the optimized algorithm. We compared test characteristics of
      the optimized algorithm, the Public Health-Seattle and King County STD Clinic's
      current 13-component algorithm, and a simple 2-component algorithm including only
      presence of symptoms and contact to STD. RESULTS: From October 2010 to June 2015,
      18,653 unique patients completed a computer-assisted self-interview. In the
      validation samples, the optimized, current, and simple algorithms appropriately
      triaged 90%, 85%, and 89% of patients, respectively. The optimized algorithm had
      lower sensitivity for identifying patients needing standard visits (men, 94%;
      women, 93%) compared with the current algorithm (men, 95%; women, 98%), as did
      the simple algorithm (men, 91%; women, 93%). The optimized, current, and simple
      algorithms triaged 31%, 23%, and 33% of patients to express visits, respectively.
      CONCLUSIONS: The overall performance of the statistically optimized algorithm did
      not differ meaningfully from a simple 2-component algorithm. In contrast, the
      current algorithm had the highest sensitivity but lowest overall performance.

PMID- 29634600
TI  - Predictors of Unplanned Reoperation After Operative Treatment of Pelvic Ring
      Injuries.
AB  - OBJECTIVES: To evaluate the incidence of unplanned reoperations after pelvic ring
      injuries and to develop a risk prediction model. DESIGN: Retrospective review.
      SETTING: Level I Trauma Center. PATIENTS: The medical records of 913 patients
      (644 male and 269 female patients; mean age, 39 years; age range, 16-89 years)
      with unstable pelvic ring fractures operatively treated at our center from 2003
      to 2015 were reviewed. INTERVENTION: Multiple logistic regression analysis was
      conducted to evaluate the relative contribution of associated clinical parameters
      to unplanned reoperations. A risk prediction model was developed to assess the
      effects of multiple covariates. MAIN OUTCOME MEASUREMENTS: Unplanned reoperation
      for infection, fixation failure, heterotopic ossification, or bleeding
      complication. RESULTS: Unplanned reoperations totaled 137 fractures, with an
      overall rate of 15% (8% infection, 6% fixation failure, <1% heterotopic
      ossification, and <1% bleeding complication). Reoperations for infection and
      fixation failure typically occurred within the first month after the index
      procedure. Four independent predictors of reoperation were open fractures,
      combined pelvic ring and acetabular injuries, abdominal visceral injuries, and
      increasing pelvic fracture grade. No independent association was shown between
      reoperation and patient, treatment, or other injury factors. CONCLUSIONS:
      Unplanned reoperations were relatively common. Infection and fixation failure
      were the most common indications for unplanned reoperations. Factors associated
      with reoperation are related to severity of pelvic and abdominal visceral
      injuries. Our findings suggest that these complications might be inherent and in
      many cases unavoidable despite appropriate current treatment strategies. LEVEL OF
      EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete
      description of levels of evidence.

PMID- 29634601
TI  - A Preoperative Planning Tool: Aggregate Anterior Approach to the Humerus With
      Quantitative Comparisons.
AB  - Extensile approaches to the humerus are often needed when treating complex
      proximal or distal fractures that have extension into the humeral shaft or in
      those fractures that occur around implants. The 2 most commonly used approaches
      for more complex fractures include the modified lateral paratricipital approach
      and the deltopectoral approach with distal anterior extension. Although the
      former is well described and quantified, the latter is often associated with
      variable nomenclature with technical descriptions that can be confusing.
      Furthermore, a method to expose the entire humerus through an anterior extensile
      approach has not been described. Here, we illustrate and quantify a technique for
      connecting anterior humeral approaches in a stepwise fashion to form an aggregate
      anterior approach (AAA). We also describe a method for further distal extension
      to expose 100% of the length of the humerus and compare this approach with both
      the AAA and the lateral paratricipital in terms of access to critical bony
      landmarks, as well as the length and area of bone exposed.

PMID- 29634602
TI  - The Effect of Under-Dosing Prophylactic Antibiotics in the Care of Open Tibial
      Fractures.
AB  - OBJECTIVES: To determine the frequency and effect of under-dosing prophylactic
      weight-based antibiotics in patients with open tibial fractures. We hypothesized
      that patients who did not receive appropriate weight-based dosing of prophylactic
      antibiotics would have higher rates of infection. DESIGN: Retrospective cohort
      study. SETTING: Level 1 Trauma Center. PATIENTS/PARTICIPANTS: Patients 18 years
      of age or older with high-grade (Gustilo-Anderson type IIIA or IIIB) open
      extraarticular tibial fractures over a 5-year period. MAIN OUTCOME: The primary
      outcome was deep infection within one year of initial injury. Appropriate weight
      based dosing of cefazolin was defined as: at least 1 g for patients <80 kg, 2 g
      for patients between 80 and 120 kg, and 3 g for patients >120 kg. RESULTS: Sixty
      three patients met the inclusion criteria; 21 (33%) were under-dosed with
      cefazolin at the time of initial presentation. Among the 20 patients who
      subsequently developed deep infection, only 55% were appropriately dosed with
      cefazolin; of the patients who did not develop deep infection, 72% were
      appropriately dosed with cefazolin (P = 0.18). Univariate analysis revealed that
      hypertension was associated with infection (P = 0.049). Multivariable logistic
      regression analysis of infection due to all organisms did not reveal a
      statistically significant reduction in the odds of infection with appropriate
      weight-based dosing of cefazolin [Odds ratio = 0.42 (95% confidence interval,
      0.12-1.48), P = 0.177]. Five of 7 (71%) of the gram positive, non-methicillin
      resistant Staphylococcus aureus, infections occurred in patients who were under
      dosed with cefazolin. Five (23.8%) of 21 patients who were under-dosed with
      cefazolin had gram-positive, non-methicillin-resistant S. aureus infections,
      compared to 2 (4.8%) of 42 patients who were appropriately dosed (P = 0.036).
      CONCLUSIONS: Under-dosing of weight-based antibiotics in the treatment of open
      fractures is common. Appropriate weight-based dosing of cefazolin for prophylaxis
      in high-grade open tibial fractures reduces the frequency of infection due to
      cefazolin-sensitive organisms. Interestingly, organisms not susceptible to
      cefazolin were responsible for the majority of infections. The effect of under
      dosing of cefazolin and other weight-based antibiotics deserves further
      investigation in larger studies. LEVEL OF EVIDENCE: Therapeutic Level III. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 29634603
TI  - Eye-Preserving Surgery Followed by Adjuvant Radiotherapy for Lacrimal Gland
      Carcinoma: Outcomes in 37 Patients.
AB  - PURPOSE: To describe the clinical outcomes of eye-preserving surgery followed by
      adjuvant radiotherapy in patients with lacrimal gland carcinoma. METHODS: Thirty
      seven patients with lacrimal gland carcinoma who underwent eye-preserving surgery
      were studied. RESULTS: At last follow up, 32 patients were alive without disease,
      3 patients were alive with disease with distant metastasis, 1 patient had died of
      disease, and 1 patient had died of other cause. The 5-year recurrence-free
      survival rate was worse in patients without than in patients with adjuvant
      radiotherapy (p = 0.001) and worse in patients with T3-T4 tumors than in patients
      with T1-T2 tumors (p = 0.027). At last follow up, 25 patients (68%) had visual
      acuity of 20/40 or better. CONCLUSIONS: In patients with lacrimal gland
      carcinoma, eye-preserving surgery and adjuvant radiotherapy is associated with
      reasonable local control rates and visual and ocular function. Postoperative
      adjuvant radiotherapy seems to enhance local control rates.

PMID- 29634604
TI  - A Prospective Randomized Comparative Clinical Trial to Analyze Pain and Surgical
      Outcomes Between Frontal Nerve Blocks and Subconjunctival Anesthesia for
      Conjunctival Mullerectomy Resection.
AB  - PURPOSE: Conjunctival Muller's muscle resection (CMMR) is a posterior approach
      surgical technique to correct blepharoptosis. The purpose of this study is to
      compare patient-reported pain scores and surgical outcomes for patients who
      received 2 different anesthetic techniques during CMMR, frontal nerve block and
      subconjunctival injection. METHODS: A prospective randomized comparative clinical
      trial enrolled 33 CMMR subjects from one tertiary eye center. Patients undergoing
      unilateral CMMR were randomized to receive either frontal nerve block or
      subconjunctival injection. For patients undergoing bilateral CMMR, each side was
      randomized to one of the injection techniques. Upper eyelid margin reflex
      distance was measured and recorded for each eye before and after surgery.
      Patients' pain scores were quantified using the Wong Baker Pain Scale. Subjects
      quantified their pain during, immediately after, 12 and 24 hours after surgery.
      RESULTS: Twenty-four bilateral and 9 unilateral cases were enrolled in the study.
      Twenty-two (92%) subjects were female, and the mean patient age was 69 +/- 12
      years. The mean margin reflex distance was 1.1 mm preoperatively, which increased
      to 3.5 and 3.6 mm 2 months postoperatively in frontal nerve block and
      subconjunctival injection groups, respectively (p value <0.0001). Both paired and
      nonpaired analyses demonstrated no significant difference in the pain score
      reported by the patients or the surgical outcomes between the 2 anesthesia
      techniques at any time during or after the surgery. There were no anesthetic
      related complications. CONCLUSION: There was no statistically significant
      difference in pain scores or surgical outcomes in patients receiving frontal
      nerve block compared with those receiving subconjunctival injection during CMMR
      surgery.

PMID- 29634605
TI  - Distribution of Adrenergic Receptor Subtypes and Responses to Topical 0.5%
      Apraclonidine in Patients With Blepharoptosis.
AB  - PURPOSE: To determine the relationship between the distribution of adrenergic
      receptors in the human eyelid and the eyelid elevation after topically instilling
      0.5% apraclonidine in blepharoptosis patients. METHODS: A total of 26
      blepharoptotic patients (30 eyelids) were included in the experimental study.
      Marginal reflex distance 1 was measured before and after topical instillation of
      0.5% apraclonidine. Eyelids were divided into 2 groups according to the responses
      to topical 0.5% apraclonidine. Patients who positively responded to apraclonidine
      were classified as group A and those that negatively responded to it were
      classified as group B. Muller's muscle was obtained during the blepharoptotic
      surgery, followed by immunohistochemical staining and scoring. This study was
      approved by the Institutional Review Board of Kim's Eye Hospital and the study
      protocol adhered to the tenets of the Declaration of Helsinki. RESULTS: alpha-1D
      staining intensity was significantly higher in group A than in B (p < 0.001) and
      alpha-2C and beta-1 staining intensities were significantly higher in group B
      than in A (p < 0.001 and p < 0.05, respectively). The difference in beta-2
      staining intensity between groups A and B was not statistically significant.
      CONCLUSIONS: alpha-1D adrenoceptor was predominant in patients showing a positive
      response to topical 0.5% apraclonidine. Because apraclonidine has an alpha-1
      agonistic effect, alpha-1D adrenoceptor may contribute to apraclonidine's
      elevating effect in patients with blepharoptosis.

PMID- 29634606
TI  - An Individualized 3-Dimensional Designed and Printed Conformer After Dermis Fat
      Grafting for Complex Sockets.
AB  - PURPOSE: To introduce a novel technique to design individually customized
      conformers for postenucleation sockets with dermis fat implants. METHODS: We use
      a 3-dimensional scan of the frontal face/orbit and eyelid contour to design an
      individualized conformer. This polymethylmetacrylate printed conformer is adapted
      to patients' socket, palpebral fissures, horizontal eyelid aperture, curvature of
      the eyelids, and mean diameter of patients' contralateral eye. Sutures through
      holes in the inferior part of the conformer and in the extension can be placed to
      fixate the conformer and anchor fornix deepening sutures. RESULTS: A correct
      fitting conformer can be printed and attached to the socket and eyelids. The
      shape of this conformer can be used subsequently postsurgically to design the
      ocular prosthesis. CONCLUSION: Presurgical planning is important to anticipate
      for a functional socket to adequately fit an artificial eye. The presented
      technique using 3-dimensional imaging, designing, and printing promises to
      prevent conformer extrusion and forniceal shortening.

PMID- 29634607
TI  - Amniotic Band Syndrome: A Review of 2 Cases.
AB  - Amniotic band syndrome is a rare congenital disorder caused by entrapment of
      fetal parts (usually a limb or digits) in fibrous amniotic bands while in utero
      that presents with complex multisystem anomalies. The authors report 2 children
      with amniotic band syndrome who presented to the ophthalmic unit of the authors'
      pediatric hospital. One of them presented with telecanthus, syndactyly, amputated
      toes, and unilateral epiphora diagnosed as congenital nasolacrimal duct
      obstruction. She was managed conservatively with lacrimal sac massage and
      provided with refractive correction while she simultaneously underwent multiple
      surgeries for correction of clubfoot and craniosynostosis. The second patient
      presented with cleft lip, cleft palate, multiple constriction bands in upper
      limbs and fingers with unilateral microphthalmos, microcornea, typical iris
      coloboma, and retinochoroidal coloboma, very similar to a case reported in
      literature. These 2 cases provide an overview of the clinical spectrum of
      ophthalmic manifestations along with their staged optimum rehabilitation.

PMID- 29634608
TI  - Herpes Zoster Ophthalmicus With Orbital Findings Preceding Skin Rash.
AB  - The authors describe 2 patients who presented with orbital findings and later
      developed vesicular lesions that were positive for varicella zoster virus and
      consistent with Herpes Zoster ophthalmicus. One case is the first to involve
      dacryoadenitis and orbital myositis preceding disseminated Herpes Zoster. In the
      other case, a patient developed zoster orbital syndrome leading to elevated
      intraocular pressure, loss of vision, and afferent pupillary defect. Canthotomy
      and cantholysis were required to restore vision. In both cases, the orbital
      syndrome developed prior to the vesicular rash. These cases highlight the need to
      consider Herpes Zoster ophthalmicus in patients with orbital syndrome not
      responding to conventional treatment.

PMID- 29634609
TI  - Ophthalmic Pyogenic Granulomas Treated With Topical Timolol-Clinical Features of
      17 Cases.
AB  - PURPOSE: Topical timolol has been increasingly demonstrated to be an effective
      treatment for pyogenic granulomas (PG). The authors review the treatment outcomes
      of 17 patients with ocular PG treated with topical timolol. METHODS:
      Retrospective interventional study of 17 patients with ocular PGs treated with
      timolol 0.5% solution. Patient demographics, clinical features, treatment
      response, and recurrence were noted. RESULTS: Nine females and 8 males with a
      mean age of 23 years (range, 3-67 years) were included. Mean duration of disease
      prior to treatment was 3.81 months (range, 0.25-11 months). Etiologies included
      chalazia (12 cases, 71%), postsurgical (4, 24%) and trauma (1, 6%). Five patients
      (29%) had treatment with topical steroids prior to presentation. Fifteen patients
      (88%) had PG located on the palpebral conjunctiva and 2 (12%) involving the
      bulbar conjunctiva. Mean lesion size was 5.06 * 6.06 mm (range, 3-8 * 3-18 mm).
      Fifteen patients (88%) had complete lesion resolution with a mean treatment
      duration of 3.07 weeks (range, 2-5 weeks) and no adverse events or recurrences
      with a mean follow up of 9.47 months (range, 6-27 months). Two patients (12%)
      underwent lesion excision after 6 weeks of timolol failed to yield resolution.
      CONCLUSION: Topical timolol appears to be a well-tolerated nonsurgical treatment
      of ocular PG in both children and adults. Clinicians may wish to consider topical
      timolol to treat PG as opposed to topical steroids, given the inherent risk of
      steroid response ocular hypertension and the difficulty to measure intraocular
      pressure in younger children who require general anesthesia for excision.

PMID- 29634610
TI  - Absenteeism and Indirect Economic Burden Associated With Primary and Secondary
      Hypogonadism: A Retrospective Matched Cohort Analysis of Employed, Commercially
      Insured Patients in the U.S.
AB  - OBJECTIVE: The aim of this study was to evaluate the indirect economic burden
      incurred by patients with primary and secondary hypogonadism (HG) compared with
      non-HG controls using real-world data. METHODS: In this retrospective cohort
      study using a large US administrative claims database, adult males with primary
      or secondary HG were selected from 2010 to 2014. Non-HG controls had no evidence
      of HG from 2009 to 2014 and were matched on age, insurance type, and geographic
      region to HG patients. Outcomes included absenteeism and associated costs.
      RESULTS: HG (vs non-HG) patients had a significant 15% increase in
      nonrecreational absenteeism hours (adjusted odds ratio 1.15, P = 0.002) and
      associated costs ($2152 vs $1172, P < 0.001) post-index after adjusting for pre
      period differences. CONCLUSION: The indirect economic burden of HG is
      significant. Further research is needed to test whether treatment with
      testosterone can help alleviate the indirect burden associated with HG.

PMID- 29634611
TI  - Stress Among Latinos: Does it Vary by Occupation and Agricultural Season?
AB  - OBJECTIVE: Stress is pervasive among Latino immigrants. We identified seasonal
      and occupational patterns in stress among rural Latino immigrants. METHODS:
      During three agricultural periods, farmworker and non-farmworker participants
      responded to a 24-item stress questionnaire (Snipes et al, 2007). We measured the
      associations of stress with occupation, with season, and occupation within
      season, adjusting for demographic variables. RESULTS: The highest levels of
      stress were observed in the pre-thinning season when pruning takes place among
      farmworkers. Stress is significantly higher in farmworkers compared with non
      farmworkers only in the non-spray season when crops are dormant. Higher income
      was associated with decreased stress in the pre-thinning and thinning seasons
      when buds and small fruit are removed from orchards. CONCLUSIONS: Identification
      of strategies to reduce stress in Latino migrants is warranted. Although some
      sources of stress may be intractable, others may be amenable to intervention.

PMID- 29634612
TI  - The Association Between PM2.5 and Ozone and the Prevalence of Diabetes Mellitus
      in the United States, 2002 to 2008.
AB  - OBJECTIVE: To examine the association between air pollution and diabetes
      prevalence in the United States, 2002 to 2008. METHODS: Annual average
      particulate matter (PM2.5) and ozone concentrations were calculated using daily
      county-level data from the CDC's Tracking Network. Individual-level outcome and
      covariate data were obtained from the Centers for Disease Control and Prevention
      (CDC) Behavioral Risk Factor Surveillance System for 862,519 individuals. We used
      Poisson regression analyses to examine associations between each air pollutant
      (per 10-unit increase) with diabetes, including regional sub-analyses. Analyses
      were adjusted for year, age, sex, race, ethnicity, education, income, smoking
      status, body mass index, exercise, and asthma. RESULTS: Positive associations
      between each pollutant and diabetes were found (PM2.5: prevalence ratio [PR] =
      1.10; 95% confidence interval [CI] = 1.03, 1.17; ozone: PR = 1.06; 95% CI = 1.03,
      1.09). There was limited evidence of effect modification by region. CONCLUSIONS:
      Interventions to reduce ambient air pollution may help alleviate the diabetes
      burden in the US.

PMID- 29634613
TI  - Association between COMT gene polymorphisms, clinical symptoms, and cognitive
      functions in Han Chinese patients with schizophrenia.
AB  - AIM: Catechol-O-methyltransferase (COMT) gene variants may be involved in the
      pathogenesis of psychotic symptoms, and associated especially with negative
      symptom in schizophrenia, but their roles in cognitive function and treatment
      response remain unclear. The aim of this study was to explore the association
      between COMT gene polymorphisms, clinical symptoms (including cognitive
      function), and treatment response to antipsychotic medications in patients with
      schizophrenia. PATIENTS AND METHODS: A total of 200 Han Chinese inpatients with
      schizophrenia were recruited in accordance with Diagnostic and Statistical Manual
      of Mental Disorders, 4th ed. (DSM-IV). In total, 96 of them completed assessments
      at baseline and after 8 weeks of antipsychotic treatment. Clinical symptoms were
      assessed using the Positive And Negative Syndrome Scale (PANSS), and cognitive
      function was evaluated using the Verbal Fluency Test, Trail Making Test A-B,
      Stroop Color-Word Test, and Wisconsin Card Sorting Test. Two single nucleotide
      polymorphisms, rs4680 and rs165599, on the COMT gene were genotyped. RESULTS: At
      baseline, we found no significant genotypic association between rs4680 and
      clinical symptoms or cognitive function. After 8 weeks of antipsychotic
      treatment, compared with patients with GG genotype, patients with AA/AG genotypes
      at rs4680 showed significantly higher scores on PANSS total, both at baseline and
      at the end of 8 weeks, especially in negative and general psychopathology
      symptoms. Patients with GG at rs165599 scored significantly higher on the Stroop
      test, suggesting better cognitive performance after 8 weeks of treatment. No
      significant association was found between rs165599 genotype and psychiatric
      symptoms as assessed by the PANSS and cognitive function tests at baseline.
      CONCLUSION: Our findings suggest that the COMT gene polymorphisms may influence
      the response to antipsychotic treatment in Han Chinese patients with
      schizophrenia.

PMID- 29634615
TI  - Inpatient Care for the Cancer Survivor: Opportunities to Develop and Deliver
      Standards for Care.
AB  - Cancer continues to evolve from a terminal diagnosis to a chronic medical
      condition. With improved survivorship rates, opportunities exist to deliver
      rehabilitation care throughout the oncology continuum. By definition, inpatient
      rehabilitation is generally considered postacute care and is provided either in
      inpatient rehabilitation facilities, in skilled nursing facilities, or in long
      term care hospitals. Each institution is subject to specific regulations and
      legislation that help define appropriateness for admission based on diagnosis,
      medical necessity, and functional need. However, these criteria may present
      barriers to access care for the oncology survivor. As the healthcare landscape
      changes, and reimbursement structures shift from fee-for-service to those that
      emphasize effectiveness and efficiency in care, inpatient rehabilitation has a
      unique opportunity to improve value in terms of outcomes and cost. With the
      implementation of the Improving Medicare Post-Acute Care Transformation Act,
      standardization of measures throughout postacute care may allow for a more
      consistent approach to delivery of inpatient rehabilitation care. Further work
      will be necessary to define the parameters by which oncology survivors should be
      gauged in this framework.

PMID- 29634614
TI  - A Risk Scoring System for the Prediction of Functional Deterioration,
      Institutionalization, and Mortality Among Medicare Beneficiaries.
AB  - OBJECTIVE: We sought to develop a risk scoring system for predicting functional
      deterioration, institutionalization, and mortality. Identifying predictors of
      poor health outcomes informs clinical decision-making, service provision, and
      policy development to address the needs of persons at greatest risk for poor
      health outcomes. DESIGN: This is a cohort study with 21,257 community-dwelling
      Medicare beneficiaries 65 yrs and older who participated in the 2001-2008
      Medicare Current Beneficiary Survey. Derivation of the model was conducted in 60%
      of the sample and validated in the remaining 40%. Multinomial logistic regression
      model generated beta coefficients, which were used to create a risk scoring
      system. Our outcome was instrumental activity of daily living stage transitions
      (stable/improved function and functional deterioration), institutionalization, or
      mortality for 2 yrs of follow-up. RESULTS: A total of 18 factors were identified
      for functional deterioration (P < 0.05). In the derivation cohort, the likelihood
      of functional deterioration ranged from 6.27% to 33.51%, risk of
      institutionalization from 0.07% to 12.13%, and risk of mortality from 2.13% to
      31.83%, in comparison with stable/improved function. CONCLUSIONS: A risk scoring
      system predicting Medicare beneficiaries' risk of functional deterioration,
      institutionalization, and mortality based on demographic and clinical indicators
      may feasibly be developed with implications for healthcare delivery.

PMID- 29634616
TI  - Second-Order Peer Reviews of Clinically Relevant Articles for the Physiatrist: Is
      Pregabalin Effective in the Treatment of Radiating Low Back Pain Into the Leg?

PMID- 29634617
TI  - PMR Role on Notalgia Paresthetica: Case Report and Treatment Review.
AB  - Notalgia paresthetica (NP) is a rarely reported T2-T6 sensory neuropathy whose
      etiology and treatment are not fully established. Although it is believed to be
      common in dermatological practice, it remains under-recognized, under-diagnosed,
      and therefore under-reported. This case-report provides a physical medicine and
      rehabilitation (PMR) perspective on NP diagnosis and treatment. This article
      presents a case report of a 39-year-old woman with pain, pruritus, and a
      hyperpigmented area in the right dorsal infra scapular region. The diagnosis of
      NP was established. She was successfully treated with topical anesthetics,
      postural corrective exercises, scapular muscle strengthening and pectoral muscle
      stretching. In this context, different treatment options were reviewed. A small
      set of pharmacological and non-pharmacological techniques were identified.
      Several of these modalities belong to the PMR field of action.

PMID- 29634618
TI  - Ultrasound Imaging for Muscle Variations: Digastric Flexor Carpi Ulnaris,
      Gastrocnemius Tertius, and Supernumerary Fibularis Longus in an Asymptomatic
      Family.
AB  - Anatomical variations of the muscles are seen with different frequencies.
      Although most of them are asymptomatic; in certain cases, their existence
      requires attention with regard to entrapment syndromes, mass lesions, botulinum
      toxin injections, and tendon transfers. Herein, as ultrasound imaging is a
      convenient method for muscle imaging, it can easily be used in daily practice for
      prompt understanding of such muscular variations. In this report, we demonstrated
      and discussed a similar scenario in an asymptomatic individual (and his close
      family members) using ultrasound imaging for scanning the digastric flexor carpi
      ulnaris, gastrocnemius tertius, and supernumerary fibularis longus muscles.

PMID- 29634619
TI  - Cardiac and Pulmonary Cystic Echinococcosis With Massive Obstruction of the
      Pulmonary Vessel System in a 16-Year-Old Girl.
AB  - We describe herein the management of a 16-year-old girl with cystic
      echinococcosis of the right ventricle and massive obstruction of the pulmonary
      vessel system by parasitic metastatic dissemination. After resection of the
      cardiac cyst, pulmonary thromboendarterectomy was performed to remove parts of
      the obstructive parasitic material. The treatment reduced the elevated pulmonary
      arterial pressure, improving the patient's overall condition.

PMID- 29634620
TI  - Population Pharmacokinetics of Intravenous Linezolid in Premature Infants.
AB  - BACKGROUND: The emergence of coagulase-negative staphylococci (CoNS) with reduced
      vancomycin-susceptibility in some neonatal intensive care units (NICU) has
      resulted in an increase of linezolid use. Linezolid pharmacokinetics (PK) and
      safety in premature infants still need to be better established. METHODS: This
      was a retrospective PK study. All infants who received intravenous (IV) linezolid
      and had linezolid plasma concentrations per standard of care were included.
      Linezolid concentrations were measured by high-performance liquid chromatography.
      A population PK model was developed using nonlinear mixed effects modeling
      (NONMEM). Optimal dosing was determined based on achievement of the surrogate
      pharmacodynamics (PD) target for efficacy: a ratio of the area under the
      concentration-time curve (AUC) to minimum inhibitory concentration (MIC) > 80. We
      assessed the occurrence of thrombocytopenia and lactic acidosis in relation with
      drug exposure. RESULTS: A total of 78 plasma concentrations were collected from
      26 infants, with a median postnatal age (PNA) of 24 days (8-88) and weight of
      1423g (810-3256). A 1-compartment model described linezolid data well. The final
      model included PNA and weight on clearance, and weight on volume of distribution.
      Considering an MIC90 of 1 mg/L; all infants reached an AUC/MIC > 80. Although
      thrombocytopenia and hyperlactatemia occurred frequently, they were not sustained
      and were not considered related to linezolid. CONCLUSION: Intravenous linezolid
      was efficient and well tolerated in critically ill premature infants. PNA was the
      main determinant of clearance.

PMID- 29634621
TI  - Management of Stenotrophomonas maltophilia Infections in Critically Ill Children.
AB  - BACKGROUND: Stenotrophomonas maltophilia is a life-threatening nosocomial
      pathogen with profound multidrug-resistant attributes. It is associated with high
      mortality, particularly in immunocompromised patients. Data on therapy for S.
      maltophilia infections are scarce, especially in children hospitalized in
      intensive care settings (pediatric intensive care unit). METHODS: A retrospective
      chart review of pediatric patients with isolates of S. maltophilia hospitalized
      over a 5-year period in 2 pediatric intensive care units. RESULTS: Thirty-one
      patients and 91 isolates from blood, respiratory secretions and soft tissues were
      identified and reviewed. The overall incidence of S. maltophilia infections
      increased during the study period (P = 0.003). The all-cause crude mortality was
      61%, and the attributed mortality was approximately 16%. Risk factors associated
      with mortality included longer hospitalization before infection (P = 0.002),
      septic shock (P = 0.003), mechanical ventilation (P = 0.004), an indwelling
      central vein catheter (P = 0.03) and prior use of steroids (P = 0.04) and
      carbapenems (P = 0.004). On multivariate analysis, mortality was associated with
      mechanical ventilation (P = 0.02) and preinfection hospitalization days (P =
      0.01). Combination treatment of trimethoprim and sulfamethoxazole, ciprofloxacin
      and/or minocycline significantly extended survival time (P < 0.001). The method
      of treatment did not significantly affect the interval between S. maltophilia
      isolation to resolution of infection (P = 0.200). CONCLUSIONS: Combinations of
      trimethoprim and sulfamethoxazole, ciprofloxacin and minocycline are proposed for
      pediatric intensive care unit patients harboring S. maltophilia. Meticulous
      evaluation of central vascular access and prior treatment with carbapenems are
      indicated, especially for mechanically ventilated and septic children.

PMID- 29634622
TI  - Selected Children with Complicated Acute Urinary Tract Infection May be Treated
      with Outpatient Parenteral Antibiotic Therapy at Home Directly from the Emergency
      Department.
AB  - BACKGROUND: Outpatient parenteral antimicrobial therapy (OPAT) offers the option
      of treating children requiring intravenous antibiotics for acute urinary tract
      infection(UTI)/pyelonephritis at home. We aimed to determine the outcomes of
      treating patients with UTI/pyelonephritis using OPAT directly from the Emergency
      Department (ED) without admission to hospital. METHODS: This was a retrospective
      study (Aug 2012-Jul 2016) of children with UTI/pyelonephritis treated with
      parenteral antibiotics via a peripheral cannula directly from ED to home under a
      hospital-in-the home (HITH) program. Data collection included demographics,
      clinical features, length of stay, complications and readmissions to hospital.
      RESULTS: There were 62 patient episodes of UTI/pyelonephritis transferred
      directly from ED to HITH. 58 (94%) had systemic features including fever,
      vomiting, and/or tachycardia. 18 (29%) patients had an underlying condition. 9
      (15%) received intravenous fluids and 8 (13%) antiemetics in ED. The OPAT course
      was successfully completed in 56 (90%) patients. Of 6 (10%) patients who were
      readmitted, 2 were discharged within 24 hours and none were severely unwell. 2
      (3%) had a blocked cannula, with no antibiotic complications. HITH patients were
      treated for a combined total of 142 days at home resulting in a cost saving of
      AUD108,914 (USD82,775). However, only 8% of children deemed to require a course
      of IV antibiotics were transferred directly home from ED. Compared to patients
      concurrently admitted to hospital, fewer on HITH less than 1 year of age (13%
      versus 33%, OR 0.3, p<0.01). CONCLUSIONS: Selected patients presenting to ED with
      UTI/pyelonephritis may be treated directly via HITH, including some with
      underlying conditions and/or systemic features.

PMID- 29634623
TI  - Optimum Detection of Ureaplasma in Premature Infants.
AB  - BACKGROUND: Ureaplasma spp. is a known risk factor for bronchopulmonary dysplasia
      in premature infants. Emerging research suggests treatment with azithromycin or
      clarithromycin in the first days of life (DOLs) reduces bronchopulmonary
      dysplasia in Ureaplasma spp. positive infants. Side effects of these antibiotics
      make it imperative to optimize reliable noninvasive screening procedures to
      identify infants who would benefit from treatment. METHODS: The aim of this study
      was to determine the best site and time to screen for Ureaplasma spp. in 24- to
      34-week premature infants. Oral, nasal, gastric and tracheal cultures were
      collected and placed immediately in 10B broth media. Polymerase chain reaction
      verified culture results and identified the Ureaplasma spp. RESULTS: Cultures
      yielded a Ureaplasma spp. incidence of 80/168 = 47.6% [95% confidence interval
      (CI): 40-56]. Nasal cultures had greater sensitivity to detect Ureaplasma spp.
      than oral cultures (P = 0.008): however, a significant proportion of infants with
      Ureaplasma spp. would have been missed (12/79 = 15.2%, 95% CI: 8%-25%, P < 0.001)
      if oral cultures were not obtained. For all sites, the collection at DOL 7-10
      were more likely to be positive than the collection at DOL 1-2: however, a
      significant proportion (5/77 = 6.5%, 95% CI: 2-15, P < 0.001) of infants with
      Ureaplasma spp. would have been missed if the DOL 1-2 cultures were not obtained.
      CONCLUSIONS: For optimal Ureaplasma spp. detection in 24- to 34-week premature
      infants, cultures need to be taken both early and late in the first 10 DOLs both
      from nasal and oral secretions.

PMID- 29634624
TI  - Perinatal Yellow Fever: A Case Report.
AB  - An outbreak of yellow fever in Brazil made it possible to assess different
      presentations of disease such as perinatal transmission. A pregnant woman was
      admitted to hospital with yellow fever symptoms. She was submitted to cesarean
      section and died due to fulminant hepatitis. On the 6th day the newborn developed
      liver failure and died 13 days later. Yellow fever PCR was positive for both.

PMID- 29634625
TI  - An 8-year-old Boy With Fever and Abdominal Pain.

PMID- 29634626
TI  - Epidemiology of Otitis Media With Otorrhea Among Bangladeshi Children: Baseline
      Study for Future Assessment of Pneumococcal Conjugate Vaccine Impact.
AB  - BACKGROUND: Otitis media (OM) poses a high disease burden on Bangladeshi
      children, but little is known about its etiologies. We conducted a surveillance
      study in the largest pediatric hospital to characterize pathogens responsible for
      OM. METHODS: In the outpatient ear-nose-throat department of Dhaka Shishu
      Hospital, which serves 0 to 18-year-old children, we collected ear swabs from OM
      children with otorrhea from April 2014 to March 2015. We cultured all specimens
      for bacterial pathogens and assessed serotype and antimicrobial susceptibility of
      Streptococcus pneumoniae (Spn) and Haemophilus influenzae (Hi) isolates. RESULTS:
      We recorded 1111 OM episodes; 88% (981/1111) involved otorrhea, and we collected
      samples from 91% (891/981) of these children. Fifty-one percent (452/891) were
      culture positive (contaminants excluded), with Hi (21%, 187/891) and Spn (18%,
      164/891) most commonly detected. Overall, 45 distinct single and mixed pathogens
      were revealed. Dominant pneumococcal serotypes were 19A, 19F, 3 and 14; 98% of Hi
      isolates were nontypeable. Pneumococcal conjugate vaccine (PCV)10 and PCV10 + 6A
      serotypes accounted for 8% and 9% of all OM and 46% and 49% of pneumococcus
      positive cases, respectively, and were more likely to be nonsusceptible to at
      least 1 antibiotic (erythromycin and/or trimethoprim-sulfamethoxazole) than
      nonvaccine serotypes (91% vs. 77%). Staphylococcus aureus (9%, 83/891) and
      Pseudomonas aeruginosa (4%, 38/891) were also found. CONCLUSIONS: Nontypeable Hi
      (NTHi) and Spn are predominant causes of OM in Bangladesh. PCV10, introduced in
      March 2015, is likely to reduce pneumococcal and overall OM burden. Data
      collected post-PCV10 will provide comprehensive insight into the effects of this
      vaccine on these pathogens.

PMID- 29634628
TI  - An Introduction to the Point/Counter-Point/Reply Exchange by Dr Stone and
      Professor Lu and Colleagues.

PMID- 29634629
TI  - In Search of a Pony: Sources, Methods, Outcomes, and Motivated Reasoning.
AB  - It is highly desirable to be able to evaluate the effect of policy interventions.
      Such evaluations should have expected outcomes based upon sound theory and be
      carefully planned, objectively evaluated and prospectively executed. In many
      cases, however, assessments originate with investigators' poorly substantiated
      beliefs about the effects of a policy. Instead of designing studies that test
      falsifiable hypotheses, these investigators adopt methods and data sources that
      serve as little more than descriptions of these beliefs in the guise of analysis.
      Interrupted time series analysis is one of the most popular forms of analysis
      used to present these beliefs. It is intuitively appealing but, in most cases, it
      is based upon false analogies, fallacious assumptions and analytical errors.

PMID- 29634627
TI  - Near Real-time Surveillance for Consequences of Health Policies Using Sequential
      Analysis.
AB  - BACKGROUND: New health policies may have intended and unintended consequences.
      Active surveillance of population-level data may provide initial signals of
      policy effects for further rigorous evaluation soon after policy implementation.
      OBJECTIVE: This study evaluated the utility of sequential analysis for
      prospectively assessing signals of health policy impacts. As a policy example, we
      studied the consequences of the widely publicized Food and Drug Administration's
      warnings cautioning that antidepressant use could increase suicidal risk in
      youth. METHOD: This was a retrospective, longitudinal study, modeling prospective
      surveillance, using the maximized sequential probability ratio test. We used
      historical data (2000-2010) from 11 health systems in the US Mental Health
      Research Network. The study cohort included adolescents (ages 10-17 y) and young
      adults (ages 18-29 y), who were targeted by the warnings, and adults (ages 30-64
      y) as a comparison group. Outcome measures were observed and expected events of 2
      possible unintended policy outcomes: psychotropic drug poisonings (as a proxy for
      suicide attempts) and completed suicides. RESULTS: We detected statistically
      significant (P<0.05) signals of excess risk for suicidal behavior in adolescents
      and young adults within 5-7 quarters of the warnings. The excess risk in
      psychotropic drug poisonings was consistent with results from a previous, more
      rigorous interrupted time series analysis but use of the maximized sequential
      probability ratio test method allows timely detection. While we also detected
      signals of increased risk of completed suicide in these younger age groups, on
      its own it should not be taken as conclusive evidence that the policy caused the
      signal. A statistical signal indicates the need for further scrutiny using
      rigorous quasi-experimental studies to investigate the possibility of a cause-and
      effect relationship. CONCLUSIONS: This was a proof-of-concept study. Prospective,
      periodic evaluation of administrative health care data using sequential analysis
      can provide timely population-based signals of effects of health policies. This
      method may be useful to use as new policies are introduced.

PMID- 29634630
TI  - Counter-Point: Early Warning Systems Are Imperfect, but Essential.
AB  - Sequential analysis can be used as an early warning system about potential
      unintended consequences of health policy decisions, generating follow-up
      investigations, but it should not be used as causal evidence.

PMID- 29634632
TI  - Honest Opinion Versus Dishonest Analysis.
AB  - Response to the response of Kuldorff and Lu et al.

PMID- 29634631
TI  - Counter-Point: Staying Honest When Policy Changes Backfire.
AB  - Despite the good intentions of the Food and Drug Administration (FDA), many drug
      warnings are ineffective or have unintended consequences, particularly if the
      media exaggerates the messages and scares the public. The controversial 2003 to
      2004 FDA warnings on youth suicidality associated with antidepressant use are a
      case in point. In a 10-year interrupted time series (ITS) analysis in 11 health
      plans, we found that the warnings and hyped media coverage led to substantial
      reductions in antidepressant use (declines in antidepressant use and overall care
      corroborated in several studies), and small, visible increases in emergency room
      and inpatient poisonings with psychotropic drugs. In a gross misunderstanding of
      the method, Dr Stone calls ITS, "an intuition based upon false analogies,
      fallacious assumptions and analytical error." We demonstrate visually using
      published studies that the ITS method is one of the oldest (hundreds of years)
      and strongest quasi-experimental study designs, and that the alternative data
      analyses proposed by Dr Stone do not have rates (denominators), nor baselines, so
      the measures of change are invalid.

PMID- 29634633
TI  - Distribution of Visits for Chronic Conditions Between Primary Care and Specialist
      Providers in Medicare Shared Savings Accountable Care Organizations.
AB  - BACKGROUND: Medicare Shared Savings Program Accountable Care Organizations (ACOs)
      may focus more on primary care given ACO financial incentives. We examine
      variation in primary care treatment of 8 prevalent chronic conditions across ACOs
      and the factors affecting the variation, and compare the role of primary care in
      ACOs and non-ACOs. RESEARCH DESIGN: We conduct regression models at the ACO-level
      to identify factors predicting higher proportions of chronic condition visits
      delivered by primary care providers (PCPs) using 2013 Medicare claims and
      enrollment data. We compare the distribution of visits to PCPs, specialists and
      advanced practice providers between ACO-attributed and non-ACO-attributed
      beneficiaries. RESULTS: At the ACO-level, the proportion of patients who are
      white and of the local population who are college educated, the complexity of the
      patient population, and the supply of specialists were negatively associated with
      the proportion of chronic condition visits delivered by PCPs, whereas the
      percentage of contracted physicians within the ACO who were PCPs was positively
      associated. These results varied when subanalyses were conducted for each
      specific chronic condition. ACO care for chronic conditions was managed similar
      to that of care for non-ACO Medicare beneficiaries in 2013, but that some ACOs
      utilize PCPs to manage chronic conditions more than others. CONCLUSIONS: Many
      ACOs may underutilize PCPs, and thus could actively shift care to less expensive
      primary care for potential savings to payers. Barriers to that shift could
      include low numbers of PCPs contracted in the ACO, and existing referral patterns
      and patient relationships with specialists.

PMID- 29634634
TI  - Immune privilege: failure of immunotherapy in controlling metastatic cutaneous
      melanoma to the eye.
AB  - This report concerns a 49-year-old female with cutaneous malignant melanoma and
      systemic metastases. These resolved following combination immunotherapy with
      ipilimumab and nivolumab. She subsequently experienced unilateral floaters, an
      increase in iris pigmentation and pigmentary glaucoma. The eye progressively lost
      vision and became painful due to iris neovascularization. The clinical diagnosis
      was of cutaneous melanoma metastatic to the vitreous, ciliary body and iris.
      Enucleation was performed for symptom control, with histopathology confirming the
      clinical diagnosis. The immune privilege of the eye may preclude ocular
      metastasis control with immunotherapy. Ocular symptoms in such patients merit
      referral to an ophthalmologist.

PMID- 29634635
TI  - Clinicopathological significance of tumor-infiltrating lymphocytes and programmed
      death-1 expression in cutaneous melanoma: a comparative study on clinical
      subtypes.
AB  - Interactions between immune cells and tumor cells play an important role in tumor
      progression. We evaluated patterns of tumor-infiltrating lymphocytes (TILs) and
      programmed death-1 (PD-1) expression in acral and nonacral cutaneous melanoma,
      and determined their effects on clinicopathological characteristics and biologic
      responses. We identified 122 cases of cutaneous melanoma, of which 39 were cases
      of non-nail unit acral melanoma (NNUAM), 35 were cases of nail unit melanoma
      (NUM), and 48 were cases of nonacral melanoma. Clinicopathological features and
      survival outcomes were analyzed according to the scores for TILs and PD-1
      expression in intratumoral and peritumoral compartments. The effects of the
      presence of TILs and PD-1 expression on various clinicopathological factors
      differed according to the clinical subtypes of cutaneous melanoma. The frequency
      of intratumoral TILs and PD-1 expression were lower in NUM than in the other two
      subtypes. The density of peritumoral PD-1 was significantly higher in NNUAM. In
      NUM and nonacral melanoma, a low density of intratumoral TILs and PD-1 was
      associated with a deeper Breslow thickness and the presence of a vertical growth
      phase. In NNUAM, a high density of peritumoral TILs and PD-1 was associated with
      a shallower Breslow thickness and less frequent extracutaneous dissemination. In
      NNUAM, a high density of peritumoral PD-1 was associated with a better prognosis.
      This study suggests that the effects of PD-1+ TILs on biological activity differ
      according to the clinical subtypes of cutaneous melanoma.

PMID- 29634637
TI  - Older women do not have seasonal variations of vitamin D levels: a study from a
      southern country.
AB  - OBJECTIVE: The aim was to study whether the seasonal variation of vitamin D
      [25(OH)-D or calcidiol] is similar or different in younger and older women living
      in a southern country. METHODS: Measurement of serum 25(OH)-D concentration in
      739 Chilean women aged 20 to 87 years, residents of Santiago (latitude: 33.4
      degrees  South) who, during a routine gynaecological checkup, agreed to be
      evaluated. RESULTS: The mean serum concentration of 25(OH)-D for the group was
      24.1 +/- 10.5 ng/mL. In women 20 to 39 years, the mean was significantly
      different from the mean of the >=60 years old group (25.8 +/- 10.6 ng/mL vs 23.9
      +/- 11.1 ng/mL; P < 0.02). Globally, 38.4% of participants had vitamin D
      deficiency and 36.1% insufficiency. A deficiency was present in 28.4% of the 20
      to 39 years old, and in 43.9% in the >=60 years old group (P < 0.004). In the
      whole group, a lower proportion (P < 0.0001) of vitamin D deficiency cases in the
      youngest women occurred during the summer (23.7%) in comparison to the winter
      (47.7%). It was observed that the proportion of participants in the 20 to 39
      years old group with vitamin D deficiency fell from 48.9% in winter to 4.9% in
      summer (P = 0.0001). In the older groups, this change (less deficiency) is
      progressively smaller, 51.2% to 27.6% (P = 0.0020) in women 40 to 59 years old,
      and it does not happen in women >=60 years (40% with vitamin D deficiency).
      CONCLUSIONS: Serum vitamin D deficiency [25(OH)-D or calcidiol] is highly
      prevalent in Santiago, especially in older women (>=60 y) throughout the year. In
      contrast, in younger women (<40 y), the vitamin D deficiency tends to disappear
      during summer. More epidemiological studies and targeted prevention actions on
      vitamin D deficiency are warranted.

PMID- 29634636
TI  - Vascular dysfunction across the stages of the menopausal transition is associated
      with menopausal symptoms and quality of life.
AB  - OBJECTIVE: The menopausal transition is associated with somatic symptoms and
      increased rates of depression, which can impair quality of life (QOL) and
      increase cardiovascular disease (CVD) risk. This period is also associated with
      accelerated vascular aging (arterial stiffening and endothelial dysfunction), an
      antecedent to CVD. This secondary analysis sought to explore associations between
      depression, menopausal symptoms and QOL, and vascular aging across menopause
      stages. METHODS: Arterial stiffness (carotid artery compliance), endothelial
      function (brachial artery flow-mediated dilation [FMD]), menopausal symptoms
      (Menopausal Symptom List [MSL]), depression (Center for Epidemiologic Studies
      Depression Scale [CES-D]), and QOL (Utian QOL Scale [UQOL]) were measured in 138
      women (19-70 years) classified as premenopausal (n = 41, 34 +/- 8 years; mean +/-
      SD), early (n = 25, 49 +/- 3 years), or late perimenopausal (n = 26, 50 +/- 4
      years), or early (n = 22, 55 +/- 4 years) or late postmenopausal (n = 24, 61 +/-
      5 years). Differences across menopause stages were determined using one-way
      analysis of variance; associations between vascular measures and MSL, CES-D, and
      UQOL were tested using Pearson's correlation analyses. RESULTS: Menopausal
      symptoms, depression, and QOL worsened across menopause stages, particularly in
      late perimenopausal women. Vasosomatic symptom frequency, and general somatic
      symptom frequency and severity were inversely correlated with carotid artery
      compliance and FMD (r = -0.27 to -0.18, all P < 0.05). Only correlations with
      general somatic symptoms were significant after adjusting for multiple
      comparisons. Total QOL was positively correlated with carotid artery compliance
      (r = 0.23, P = 0.01). CES-D scores were not correlated with carotid artery
      compliance or FMD (r = -0.08, -0.03, P = 0.35). CONCLUSIONS: Vascular dysfunction
      across the stages of menopause was associated with greater frequency and severity
      of menopausal symptoms, and lower QOL, but not depression. Mechanisms underlying
      these associations (eg, inflammation, oxidative stress) should be explored.

PMID- 29634638
TI  - Balance ability and posture in postmenopausal women with chronic pelvic pain.
AB  - OBJECTIVE: The aim of the present study was to analyze balance ability and
      posture in postmenopausal women with chronic pelvic pain (CPP). METHODS: This
      study includes a sample of 48 women with CPP recruited from the Gynecology
      Service of Virgen de las Nieves and San Cecilio Hospitals in Granada (Spain) and
      48 healthy control women matched with respect to age and anthropometric
      characteristics. Outcome variables collected included: balance ability (Mini
      Balance Evaluation Systems Test and Timed Up an Go Test) and posture
      (photogrammetry and Spinal Mouse). RESULTS: Significant differences were found in
      all Mini Best Test subscales: total (P < 0.001), anticipatory (P = 0.002),
      reactive postural control (P < 0.001), sensory orientation (P < 0.001), and
      dynamic gait (P < 0.001), and all Timed Up and Go test subscales: alone (P <
      0.001), with manual (P = 0.002) and cognitive task (P = 0.030). Significant
      differences were also found on spinal cervical angles with a forward head posture
      in women with CPP; global spine alignment exhibited more deviation in the women
      with CPP (P < 0.001); and a higher percentage of women with CPP (58%) presented
      with increased thoracic kyphosis and lumbar lordosis. Cohen's d was used to
      calculate the effect size. Some subscales of balance and posture tests showed a
      large effect size (d >=0.8), indicating a more consistent result. CONCLUSIONS:
      Women with CPP presented poor balance including anticipatory, reactive postural
      control, sensory orientation, dynamic gait, and dual task-related conditions.
      Posture showed higher values on the dorsal angle and lower sacral inclination,
      less spine alignment, and a more prevalent posture with increased kyphosis and
      lumbar lordosis.

PMID- 29634639
TI  - Temporal Changes in Cardiovascular Remodeling Associated with Football
      Participation.
AB  - PURPOSE: American-style football (ASF) participation rates in the United States
      are highest among high school (HS) athletes. This study sought to compare the
      cardiovascular response to HS versus collegiate ASF participation. METHODS: The
      ASF participants (HS, n = 61; collegiate, n = 87) were studied at preseason and
      postseason time points with echocardiography and applanation tonometry. Primary
      outcome variables included: left ventricular (LV) mass index, LV diastolic
      function (early relaxation velocity [E']), and arterial stiffness (pulse wave
      velocity [PWV]). RESULTS: High school (17.1 +/- 0.4 yr) and collegiate ASF
      participants (18 +/- 0.4 yr) experienced similar LV hypertrophy (DeltaLV mass HS
      = 10.5 +/- 10 vs collegiate = 11.2 +/- 13.6 g.m, P = 0.97). Among HS
      participants, increases in LV mass were associated with stable diastolic tissue
      velocities (DeltaE' = -0.3 +/- 2.9 cm.s, P = 0.40) and vascular function
      (DeltaPWV = -0.1 +/- 0.6 m.s, P = 0.13). In contrast, collegiate participants
      demonstrated a higher burden of concentric LV hypertrophy (21/87, 24% vs 7/61,
      11%, P = 0.026) with concomitant reductions in diastolic tissue velocities
      (DeltaE': -2.0 +/- 2.7 cm.s, P < 0.001) and increased arterial stiffness
      (DeltaPWV: Delta0.2 +/- 0.6 m.s, P = 0.003), changes that were influenced by
      linemen who had the highest post-season weight (124 +/- 10 kg) and systolic blood
      pressure ([SBP], 138.8 +/- 11 mm Hg). In multivariable analyses adjusting for age
      and ethnicity, body mass was an independent predictor of post-season PWV (beta
      estimate = 0.01, P = 0.04) and E' (beta estimate = -0.04, P = 0.05), whereas SBP
      was an independent predictor of postseason LV mass index (beta estimate = 0.18, P
      = 0.01) and PWV (beta estimate = 0.01, P = 0.007). CONCLUSIONS: The transition
      from HS to college represents an important physiologic temporal data point after
      which differential ASF cardiovascular phenotypes manifest. Future work aimed to
      clarify underlying mechanisms, and the long-term clinical implications of these
      findings is warranted.

PMID- 29634640
TI  - Effects of Neuromuscular Electrical Stimulation in People with Spinal Cord
      Injury.
AB  - INTRODUCTION: Muscle force production is usually impaired in people with spinal
      cord injury (SCI). The use of high-intensity neuromuscular electrical stimulation
      (NMES) strength training can help promote metabolically active lean muscle mass
      and, thus, increase muscle mass and improve physical health and quality of life
      (QoL). Nonetheless, NMES is usually used at low-stimulation intensities, and
      there is limited evidence on the effects of high-intensity NMES strength training
      into improving muscle force and mass, symptoms of spasticity, or physical health
      and QoL in people with SCI. METHODS: Five individuals with chronic SCI completed
      five 10-repetition sets of high-intensity knee extension NMES strength training
      sessions for 12 wk in both quadriceps muscles. Quadriceps femoris (QF) knee
      extensor torque was measured on a dynamometer, and cross-sectional area (CSAQF)
      was measured with extended field-of-view ultrasonography. Venous blood samples
      were collected for blood lipid profiling and C-reactive protein analyses. The
      Spinal Cord Injury Spasticity Evaluation Tool was used to assess symptoms of
      spasticity, and the QoL index SCI version III was used for QoL measures. RESULTS:
      QF tetanic knee extensor torque increased on average by 35% (2%-92%), and CSAQF
      increased by 47% (14%-145%). A significant increase in the HDL/LDL cholesterol
      ratio (P < 0.001) and a mean significant improvement of 4.8% +/- 2.3% (absolute
      value = 0.26) in the Spinal Cord Injury Spasticity Evaluation Tool score was
      observed, whereas QoL showed a near-significant improvement in the health and
      functioning domain (15.0 +/- 4.2 and 17.3 +/- 5.1; P = 0.07). CONCLUSIONS: High
      intensity NMES strength training in people with SCI may improve muscle strength,
      mass, physical health, and QoL. However, replication of these results is
      necessary before clinical implementation.

PMID- 29634641
TI  - The Role of Task Difficulty in Learning a Visuomotor Skill.
AB  - INTRODUCTION: Task difficulty affects the amount of interpretable information
      from a task, which is thought to interfere with motor learning. However, it is
      unclear whether task difficulty in itself is a stimulus for motor learning
      because the experimental evidence is mixed in support of the optimal challenge
      point framework that predicts one specific level of task difficulty to produce
      the greatest magnitude of motor learning. PURPOSE: We determined the effects of
      functional task difficulty on motor skill acquisition, retention, and transfer.
      METHODS: Healthy young participants (N = 36) learned a mirror star-tracing task
      at a low, medium, or hard difficulty level defined by the bandwidth of the star.
      We measured skill acquisition, retention, and transfer to untrained difficulty
      levels, as well as the perceived mental workload during the task. RESULTS: Task
      difficulty affected motor performance, but did not affect motor learning and
      transfer. For the groups that practiced the task at the medium and hard but not
      at the low difficulty level, initial skill level correlated with the magnitude of
      learning. CONCLUSIONS: The optimal challenge point framework does not capture the
      complex relationship between task difficulty and motor learning. Previously
      reported effects of task difficulty on the magnitude of motor learning are
      probably mediated by perceived mental workload. Task difficulty did not affect
      the magnitude of visuomotor skill learning but it affected how learning occurred.
      The data have implications on how athletes learn new motor skills and patients
      relearn injury-impaired motor skills during rehabilitation.

PMID- 29634643
TI  - Black Carbon Reduces the Beneficial Effect of Physical Activity on Lung Function.
AB  - INTRODUCTION: When physical activity is promoted in urban outdoor settings (e.g.,
      walking and cycling), individuals are also exposed to air pollution. It has been
      reported that short-term lung function increases as a response to physical
      activity, but this beneficial effect is hampered when elevated air pollution
      concentrations are observed. Our study assessed the long-term impact of air
      pollution on the pulmonary health benefit of physical activity. METHODS: Wearable
      sensors were used to monitor physical activity levels (SenseWear) and exposure to
      black carbon (microAeth) of 115 healthy adults during 1 wk in three European
      cities (Antwerp, Barcelona, London). The experiment was repeated in three
      different seasons to approximate long-term behavior. Spirometry tests were
      performed at the beginning and end of each measurement week. All results were
      averaged on a participant level as a proxy for long-term lung function. Mixed
      effect regression models were used to analyze the long-term impact of physical
      activity, black carbon and their interaction on lung function parameters, forced
      expiratory volume in the first second (FEV1), forced vital capacity (FVC),
      FEV1/FVC, forced expiratory flow (FEF)25-75, and peak expiratory flow.
      Interaction plots were used to interpret the significant interaction effects.
      RESULTS: Negative interaction effects of physical activity and black carbon
      exposure on FEV1 (P = 0.07), FEV1/FVC (P = 0.03), and FEF25-75 (P = 0.03) were
      observed. For black carbon concentrations up to approximately 1 MUg.m, an
      additional MET.h.wk resulted in a trend toward lung function increases (FEV1,
      FEV1/FVC, and FEF25-75 increased 5.6 mL, 0.1% and 14.5 mL.s, respectively).
      CONCLUSIONS: We found that lung function improved with physical activity at low
      black carbon levels. This beneficial effect decreased in higher air pollution
      concentrations. Our results suggest a greater need to reduce air pollution
      exposures during physical activity.

PMID- 29634644
TI  - PCNA News.

PMID- 29634646
TI  - Social Support, Unstable Angina, and Stroke as Predictors of Depression in
      Patients With Coronary Heart Disease: Erratum.

PMID- 29634645
TI  - Access to Innovative Medicine: A Preventive Cardiovascular Nurses Association
      Position Statement to Reduce the Barriers.

PMID- 29634647
TI  - Council on Cardiovascular and Stroke Nursing Liaison Report.

PMID- 29634649
TI  - A Meta-ethnography of Out-of-Hospital Cardiac Arrest Survivors' Meanings on Life
      and Death.
AB  - BACKGROUND: Although out-of-hospital cardiac arrest (OHCA) survivors'
      physiological outcomes have been addressed, less is known on the holistic needs
      of individuals after OHCA, which hinders our ability to prioritize care around
      what really matters to survivors. AIM: The aim of this study was to
      interpretatively synthesize qualitative findings on OHCA survivors' perceptions
      and meanings of life and death and existential issues. METHODS: We used a meta
      ethnographic synthesis of published qualitative studies addressing the
      experiences of OHCA survivors based on a systematic literature search (CINAHL,
      PsycINFO, Scopus, PubMed). Studies were selected based on predefined
      inclusion/exclusion criteria. The identified studies were subjected to a quality
      appraisal based on the Critical Appraisal Skills Programme. RESULTS: Based on
      eligibility criteria, 6 phenomenological studies were included, of overall medium
      to high quality. One core theme, "the reality of death," and 4 main themes were
      identified: "redefining existence"; "revaluing death"; "being familiar with, yet
      oblivious of death"; and "living consciously." Emerging from the realization of
      death, the themes appeared to describe a gradual progression toward living
      consciously. CONCLUSIONS: An existential trajectory and a need for meaning are
      central in the experience of OHCA survivors. When existential issues are not
      addressed, the ongoing suffering may interfere with survivors' recovery and
      quality of life. Future research needs to address specific needs and ways to
      support survivors' meaning-making.

PMID- 29634648
TI  - Does Lifestyle Exercise After a Cardiac Event Improve Metabolic Syndrome Profile
      in Older Adults?
AB  - BACKGROUND: Exercise is a common recommendation to reduce the risk factors of
      metabolic syndrome, yet there are limited data on the influence of lifestyle
      exercise after cardiac events on metabolic syndrome factors. OBJECTIVE: The
      purpose of this study was to determine whether lifestyle exercise improves
      metabolic syndrome profile in older adults after a cardiac event. METHODS:
      Participants were from a post-cardiac-event lifestyle exercise study. Five
      metabolic syndrome factors were assessed: waist circumference, triglycerides,
      high-density lipids, glucose, and systolic and diastolic blood pressure.
      Objective measures of exercise were obtained from heart rate monitors over a
      year. Logistic regression was used to determine whether participants who engaged
      in the minimum recommendation of 130 hours of exercise or greater during the 12
      month period improved their metabolic syndrome profile by improving at least 1
      metabolic syndrome factor. RESULTS: In the sample of 116 participants (74% men;
      average age, 67.5 years), 43% exercised at the recommended amount (>=130 h/y) and
      28% (n = 33) improved their metabolic syndrome profile. After controlling for
      confounding factors of age, gender, race, diabetes, functional ability, and
      employment, subjects who exercised at least 130 hours a year were 3.6 times more
      likely to improve at least 1 metabolic syndrome factor (95% confidence interval,
      1.24-10.49). Of the 28% who improved their metabolic syndrome profile, 72%
      increased their high-density lipoprotein and 60.6% reduced their waist
      circumference and glucose. CONCLUSIONS: After a cardiac event, older patients who
      engage in lifestyle exercise at the recommended amount have improvement in their
      metabolic syndrome profile.

PMID- 29634650
TI  - Near and Distance Stereoacuity in Patients With Primary Open-angle Glaucoma.
AB  - PURPOSE: To compare near and distance stereoacuity between patients with primary
      open-angle glaucoma (POAG) and a control group, and to analyze the associations
      between stereoacuity and POAG severity. METHODS: This cross-sectional study
      compared near and distance stereoacuity between the POAG and control groups. The
      data from the POAG group were used to assess the associations between
      stereoacuity (both near and distance) and the severity of visual field (VF)
      defects (based on Hodapp-Anderson-Parrish classification and the VF index).
      RESULTS: The study included 94 eyes of 47 patients with POAG and 80 eyes of 40
      control subjects. Near and distance stereoacuity were significantly lower in the
      POAG group than in the control group (both P<0.001). Near stereoacuity worsened
      with POAG severity in terms of both the Hodapp-Anderson-Parrish classification
      and VF index (P=0.007 and P=0.049, respectively). However, distance stereoacuity
      was not associated with POAG severity for either categorization (P=0.12 and
      P=0.57, respectively). The proportions of patients with reduced near stereoacuity
      and those with a lack of distance stereoacuity were higher in the POAG group than
      in the control group. CONCLUSIONS: Near and distance stereoacuity were
      significantly lower among patients with POAG than among control subjects. Near
      stereoacuity worsened with increasing POAG severity but distance stereoacuity did
      not. However, the proportion of patients with a lack of distance stereoacuity was
      higher in the POAG group than in the control group.

PMID- 29634651
TI  - Clinical Outcome After Lateral Ulnar Collateral Ligament Reconstruction in an
      Adolescent Baseball Player: A Case Report.
AB  - Lateral ulnar collateral ligament (LUCL) reconstruction is a commonly used
      surgical procedure to treat posterolateral rotatory instability (PLRI) of the
      elbow. We report a 17-year-old right-handed pitcher with symptomatic PLRI after
      an injury to his LUCL during a baseball game. Having failed 8 months of
      conservative treatment, a LUCL reconstruction using the modified O'Driscoll
      technique was performed with the contralateral gracilis autograft. At 5-year
      follow-up, an excellent patient-reported outcome was achieved and the patient
      continued to play baseball at the recreational level. This type of injury is
      rarely reported in adolescent baseball players, and improving our knowledge of
      the long-term outcomes is crucial to assist clinicians in counseling patients
      about expectations after surgery.

PMID- 29634652
TI  - Etiology of Sudden Cardiac Arrest and Death in US Competitive Athletes: A 2-Year
      Prospective Surveillance Study.
AB  - OBJECTIVE: To determine the etiology of sudden cardiac arrest and death (SCA/D)
      in competitive athletes through a prospective national surveillance program.
      DESIGN: Sudden cardiac arrest and death cases in middle school, high school,
      college, and professional athletes were identified from July 2014 to June 2016
      through traditional and social media searches, reporting to the National Center
      for Catastrophic Sports Injury Research, communication with state and national
      high school associations, review of the Parent Heart Watch database, and search
      of student-athlete deaths on the NCAA Resolutions List. Autopsy reports and
      medical records were reviewed by a multidisciplinary panel to determine the
      underlying cause. SETTING AND PARTICIPANTS: US competitive athletes with SCA/D.
      MAIN OUTCOME MEASURES: Etiology of SCA/D. RESULTS: A total of 179 cases of SCA/D
      were identified (74 arrests with survival, 105 deaths): average age 16.6 years
      (range 11-29), 149 (83.2%) men, 94 (52.5%) whites, and 54 (30.2%) African
      American. One hundred seventeen (65.4%) had an adjudicated diagnosis, including
      83 deaths and 34 survivors. The most common etiologies included hypertrophic
      cardiomyopathy (19, 16.2%), coronary artery anomalies (16, 13.7%), idiopathic
      left ventricular hypertrophy/possible cardiomyopathy (13, 11.1%), autopsy
      negative sudden unexplained death (8, 6.8%), Wolff-Parkinson-White (8, 6.8%), and
      long QT syndrome (7, 6.0%). Hypertrophic cardiomyopathy was more common in male
      basketball (23.3%), football (25%), and African American athletes (30.3%). An
      estimated 56.4% of cases would likely demonstrate abnormalities on an
      electrocardiogram. CONCLUSIONS: The etiology of SCA/D in competitive athletes
      involves a wide range of clinical disorders. More robust reporting mechanisms,
      standardized autopsy protocols, and accurate etiology data are needed to better
      inform prevention strategies.

PMID- 29634653
TI  - Cross-Sectional Investigation of Self-reported Concussions and Reporting
      Behaviors in 866 Adolescent Rugby Union Players: Implications for Educational
      Strategies.
AB  - OBJECTIVE: To examine the self-recalled concussion and bell ringer (BR)
      prevalence, reporting rates, and reporting behaviors in adolescent rugby players.
      DESIGN: Cross-sectional survey. SETTING: School classroom. PARTICIPANTS:
      Adolescent male rugby players aged 12 to 18 years (n = 866). MAIN OUTCOME
      MEASURES: Concussion and BR prevalence, reporting rates, and reporting behaviors.
      RESULTS: The sample reported a concussion and BR prevalence rate of 40% and
      69.9%, respectively. Of these athletes with a history, 38.4% and 86.4% suffered
      recurrent concussions and BRs, respectively. The total reporting rates per 1000
      suspected concussions and BRs were 474.8 [95% confidence interval (CI), 415.4
      534.3] and 238.7 (95% CI, 217.8-259.5), respectively. The athletes highlighted
      several barriers which hindered their truthful reporting of concussion, including
      "not thinking the injury is serious enough to report" (70%), "wanting to win the
      game" (38%), and "not wanting to miss future games or training" (48%).
      CONCLUSIONS: Educational interventions are an invaluable component within a
      socioecological framework aimed at improving the concussion reporting rates of
      adolescent athletes. The self-recalled prevalence, underreporting rates, and
      behaviors of the sample are alarming, which prompts the need to further explore
      their motivational beliefs behind their decision to underreport a potential
      concussion. The information obtained can be used to tailor personalized
      interventions for specific athlete samples.

PMID- 29634654
TI  - Postmortem Vitreous Sodium and Chloride Elevate After 1 Hour and Magnesium After
      2 Hours in Bovine Eyeballs Immersed in Salt Water.
AB  - BACKGROUND: Postmortem vitreous sodium (Na) and chloride (Cl) are good ancillary
      tests in diagnosing salt-water drowning. Vitreous Na and Cl appear to elevate
      from salt-water drowning and immersion, whereas vitreous magnesium (Mg) appears
      to be unaffected by drowning, but elevates from immersion. The relative changes
      of these electrolytes during salt-water immersion are unknown, particularly with
      shorter immersion times. Understanding the relative changes may aid in the
      interpretation of vitreous electrolytes in bodies recovered from salt water. AIM:
      The aim of this study was to compare the changes of vitreous Na, Cl, and Mg when
      immersed in salt water. METHODS: Bovine eyeballs were randomized into 2 groups
      (submerged in salt water and control). The vitreous Na, Cl, and Mg from 6
      eyeballs were measured from each group (without replacement) at 1, 2, 4, and 6
      hours. RESULTS: There were no statistically significant elevations in bovine
      vitreous Na and Cl for up to 1 hour and vitreous Mg for up to 2 hours.
      CONCLUSIONS: Bovine vitreous Na and Cl elevate earlier than Mg when immersed in
      salt water. Assuming similar physical properties, an elevation in vitreous Mg in
      bodies immersed in salt water indicates the immersion effects of causing raised
      vitreous Na and Cl have started.

PMID- 29634656
TI  - Inhibiting the Inflammatory Injury After Myocardial Ischemia Reperfusion With
      Plasma-Derived Alpha-1 Antitrypsin: A Post Hoc Analysis of the VCU-alpha1RT
      Study.
AB  - BACKGROUND: Despite the benefits of reperfusion in limiting myocardial injury,
      the infarct size continues to expand after reperfusion because of secondary
      inflammatory injury. Plasma-derived alpha-1 antitrypsin (AAT) inhibits the
      inflammatory injury in myocardial ischemia and reperfusion. To explore the
      effects of plasma-derived AAT on the inflammatory response to ischemia
      reperfusion injury, we analyzed time-to-reperfusion and enzymatic infarct size
      estimates in a post hoc analysis of the VCU-alpha1RT clinical trial
      (clinicaltrials.gov NCT01936896). METHODS: Ten patients with ST-segment elevation
      acute myocardial infarction (STEMI) were enrolled in an open-label, single-arm
      treatment study of Prolastin C, plasma-derived AAT, at 60 mg/kg infused
      intravenously within 12 hours of reperfusion. Biomarkers were measured serially
      over the first 72 hours, and patients were followed clinically for the occurrence
      of new-onset heart failure, recurrent MI, or death. Twenty patients with STEMI
      who had been enrolled in previous randomized trials with identical
      inclusion/exclusion criteria and had been assigned to placebo served as
      historical controls. RESULTS: Time to percutaneous coronary intervention and time
      to drug did not significantly differ between groups. AAT-treated patients had a
      significantly shorter time-to-peak creatine kinase myocardial band (CK-MB) values
      (525 [480-735] vs. 789 [664-959] minute, P = 0.005) and CK-MB area under the
      curve (from 1204 [758-2728] vs. 2418 [1551-4289] U.day, P = 0.035), despite no
      differences in peak CK-MB (123 [30-196] vs. 123 [71-213] U/mL, P = 0.71).
      CONCLUSIONS: A single administration of Prolastin C given hours after reperfusion
      in patients with STEMI led to a significant shorter time to peak and area under
      the curve for CK-MB, despite similar peak CK-MB values. These preliminary data
      support the hypothesis that Prolastin C shortens the duration of the ischemia
      reperfusion injury in patients with STEMI.

PMID- 29634657
TI  - Muramyl Dipeptide Induces Reactive Oxygen Species Generation Through the NOD2/COX
      2/NOX4 Signaling Pathway in Human Umbilical Vein Endothelial Cells.
AB  - Vascular endothelium dysfunction caused by oxidative stress accelerates the
      pathologic process of cardiovascular diseases. NOD2, an essential receptor of
      innate immune system, has been demonstrated to play a critical role in
      atherosclerosis. Here, the aim of our study was to investigate the effect and
      underlying molecular mechanism of muramyl dipeptide (MDP) on NOX4-mediated
      reactive oxygen species (ROS) generation in human umbilical vein endothelial
      cells (HUVECs). The 2,7-dichlorofluorescein diacetate staining was to measure the
      intracellular ROS level and showed MDP-promoted ROS production in a time- and
      dose-dependent manner. The mRNA and protein levels of NOX4 and COX-2 were
      detected by real-time polymerase chain reaction and western blot. Small
      interfering RNA (siRNA) was used to silence NOD2 or COX-2 gene expression and
      investigate the mechanism of NOD2-mediated signaling pathway in HUVECs. Data
      showed that MDP induced NOX4 and COX-2 expression in a time- and dose-dependent
      manner. NOD2 knock-down suppressed upregulation of COX-2 and NOX4 in HUVECs
      treated with MDP. Furthermore, silence of COX-2 in HUVECs downregulated the NOX4
      expression after MDP stimulation. Collectively, we indicated that NOD2 played a
      leading role in MDP-induced COX-2/NOX4/ROS signaling pathway in HUVECs, which was
      a novel regulatory mechanism in the progress of ROS generation.

PMID- 29634658
TI  - Prognostic value of pretreatment PET/CT lean body mass-corrected parameters in
      patients with hepatocellular carcinoma.
AB  - OBJECTIVE: This study was designed to investigate whether pretreatment fluorine
      18-fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) lean body mass
      corrected parameters could predict the overall survival (OS) better than the
      established predictors in patients with hepatocellular carcinoma (HCC). PATIENTS
      AND METHODS: We retrospectively analyzed 61 patients with HCC with pretreatment F
      FDG-PET/CT. Besides obtaining clinical factors, we measured both lean body mass
      corrected and body weight-corrected PET/CT parameters, including metabolic tumor
      volume, maximal standardized uptake value of the tumor, total lesion glycolysis,
      tumor-to-normal liver uptake ratio, and so on. The prognostic value of those
      factors for OS was assessed by statistical software. RESULTS: In the univariate
      analysis, PET/CT parameters, ascites, serum alpha-fetoprotein, alkaline
      phosphatase, aspartate transaminase (AST), tumor number, tumor size of the
      maximal one, vascular invasion, TNM stage, Child-Pugh class, Barcelona Clinic
      Liver Cancer (BCLC) staging, and Okuda staging were significant predictors of OS.
      In multivariate and Kaplan-Meier analyses, lean body mass-corrected maximum
      standardized uptake value (lbmSUVmax) more than 3.35 g/ml, AST more than 42.00
      U/l, and BCLC staging B-C were significant independent predictors of poor OS.
      When BCLC staging variable was stratified by four categories instead of two in
      the multivariate analysis, it was not the statistically significant independent
      predictor anymore, but lbmSUVmax and AST still were. CONCLUSION: Pretreatment F
      FDG-PET/CT lean body mass-corrected parameters can predict the OS in patients
      with HCC. Moreover, lbmSUVmax and AST, as the independent predictors of OS, could
      supplement the prognostic value of the BCLC staging system.

PMID- 29634659
TI  - Diagnostic value of 18F-FDG PET/MRI in recurrent pelvis malignancies of female
      patients: a systematic review and meta-analysis.
AB  - The aim of this study was to assess the diagnostic performance of fluorine-18
      fluorodeoxyglucose (F-FDG) PET/MRI for suspected recurrence of pelvis
      malignancies of female patients using a meta-analysis. We performed a
      systematical literature search for relevant studies in PubMed, Cochrane Library,
      Google Scholar, and several Chinese databases. Quality Assessment of Diagnostic
      Accuracy Studies (QUADAS-2) was used to assess the quality of all included
      studies. Pooled sensitivity, specificity, positive likelihood ratio, negative
      likelihood ratio, and diagnostic odds ratio were calculated per patient and per
      lesion. Summary receiver operating characteristic curves were also constructed.
      All procedures involving human participants in this study were performed in
      conformity with the ethical standards of the institutional research committee and
      with the 1964 Helsinki Declaration and its later amendments. Finally, seven
      articles comprising 257 patients and 695 lesions were included in this meta
      analysis. On patient-based analysis, the pooled sensitivity, specificity,
      positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio
      of F-FDG PET/MRI in detecting recurrence of pelvis malignancies were 0.96 [95%
      confidence interval (CI): 0.93-0.99], 0.95 (95% CI: 0.87-0.99), 9.85 (95% CI:
      4.62-21.00), 0.07 (95% CI: 0.04-0.13), and 201.41 (95% CI: 62.89-645.03),
      respectively. On lesion-based analysis, the corresponding estimates were 0.99
      (95% CI: 0.97-1.00), 0.94 (95% CI: 0.89-0.97), 17.11 (95% CI: 4.46-65.60), 0.02
      (95% CI: 0.01-0.05), and 1125.24 (95% CI: 211.46-5987.79), respectively. The
      results of our meta-analysis indicate that F-FDG PET/MRI has excellent diagnostic
      performance in restaging female patients with suspected recurrence of
      gynecological pelvic malignancies.

PMID- 29634660
TI  - Dolutegravir resistance mutations: lessons from monotherapy studies.
AB  - PURPOSE OF REVIEW: Dolutegravir (DTG) is a second-generation integrase strand
      transfer inhibitor (InSTI) with an outstanding antiviral potency, good
      tolerability, good pharmacokinetic profile with a lack of major drug-drug
      interactions, and a barrier to resistance higher than the other compounds of the
      class (raltegravir and elvitegravir) and allegedly as high as that of boosted
      protease inhibitors. For these reasons, DTG, after successful results in a
      context of triple therapy in various clinical scenarios, has been investigated
      mostly by independent investigators in less-drug regimens, including dolutegravir
      monotherapy, in the context of a growing clinical interest for adjusting
      successful antiretroviral therapy to the increasing number of limitations for
      standard antiretroviral therapy in some HIV-infected patients. However, the
      development of genotypic resistance in case of failure to DTG monotherapy was
      unexpected. RECENT FINDINGS: Data on efficacy and resistance from preclinical
      studies, randomized clinical trials and clinical cohorts of HIV-infected patients
      treated with DTG monotherapy published in indexed journals or presented at
      international meetings were reviewed. SUMMARY: Monotherapy with dolutegravir has
      a high rate for resistance selection in the integrase gene through different
      pathways in case of virological failure.

PMID- 29634662
TI  - Fine mapping of epistatic genetic determinants of blood pressure on rat
      chromosome 5.
AB  - BACKGROUND: Previously, using linkage analysis and substitution mapping, two
      closely-linked interactive blood pressure quantitative trait loci (QTLs), BP QTL1
      and BP QTL2, were located within a 13.96 Mb region from 117894038 to 131853815 bp
      (RGSC 3.4 version) on rat chromosome 5 (RNO5). This was done by using a series of
      congenic strains consisting of genomic segments of the Dahl salt-sensitive (S)
      rat substituted with that of the normotensive Lewis (LEW) rat. The interactive
      nature of the two loci was further confirmed by the construction and
      characterization of a panel of S.LEW bicongenic strains and corresponding S.LEW
      monocongenic strains, which provided definitive evidence of epistasis (genetic
      interaction) between BP QTL1 (7.77 Mb) and BP QTL2 (4.18 Mb). The purpose of this
      work was to further map these interacting QTLs. METHOD: A new panel of seven new
      S.LEW bicongenic strains was constructed and characterized for BP. RESULTS: The
      data obtained from these new strains further resolved BP QTL1 from 7.77 to 2.93
      Mb. Further, BP QTL2 was traceable as not being a single QTL, but a composite of
      at least three QTLs, LEW alleles at two of which located within 2.26 Mb and 175
      kb lowered BP but the third one located within 1.31 Mb increased BP. CONCLUSION:
      Lack of coding variation within any of the regions further mapped within the
      previous QTL2 suggests noncoding variation as likely responsible for the observed
      epistasis.

PMID- 29634661
TI  - Blood pressure and mortality in a prospective cohort of HIV-infected adults in
      Port-au-Prince, Haiti.
AB  - OBJECTIVE: The objective of this study was to determine how baseline blood
      pressure and incident hypertension related to antiretroviral therapy (ART)
      initiation, HIV-related inflammation and mortality in HIV-infected adults in a
      low-income country. METHODS: We conducted long-term follow-up of HIV-infected
      adults who had participated in a trial of early vs. delayed initiation of ART in
      Port-au-Prince, Haiti. Between 2005 and 2008, 816 HIV-infected adults were
      randomized to early (N = 408) vs. delayed ART (when CD4 cell count <200 cells/MUl
      or AIDS-defining condition; N = 408). Blood pressure was measured every 3 months.
      Hypertension was diagnosed according to the Joint National Committee (JNC-7)
      guidelines. Biomarkers of inflammation and coagulation were measured from banked
      enrolment plasma samples. Survival analyses were performed using Stata 14.
      RESULTS: The median age at enrolment was 39 years. The median follow-up time was
      7.3 years. The hypertension incidence rate was 3.41 per 100 person-years, and was
      similar in early and delayed ART groups. In multivariable models, independent
      predictors of incident hypertension were older age, higher BMI and plasma
      interleukin (IL)-6 levels (adjusted hazard ratio, aHR = 1.23, P < 0.001).
      Systolic pressure more than 140 mmHg at enrolment was associated with increased
      mortality (aHR = 2.47, P = 0.03) as was systolic pressure less than 90 mmHg (aHR
      = 2.25, P = 0.04). Prevalent and incident hypertension were also significantly
      associated with mortality. CONCLUSION: In a large prospective study of HIV
      infected adults, we found a high incidence of hypertension associated with HIV
      related inflammation. Baseline hypertension conferred a more than two-fold
      increased risk of death. Among HIV-infected adults in low-income countries,
      hypertension should be considered a serious threat to long-term survival.

PMID- 29634663
TI  - Obesity and cardiovascular risk: a call for action from the European Society of
      Hypertension Working Group of Obesity, Diabetes and the High-risk Patient and
      European Association for the Study of Obesity: part A: mechanisms of obesity
      induced hypertension, diabetes and dyslipidemia and practice guidelines for
      treatment.
AB  - : Obesity is a key factor for cardiovascular diseases and complications. Obesity
      is associated with hypertension, dyslipidemia and type II diabetes, which are the
      major predictors of cardiovascular disease in the future. It predisposes for
      atrial fibrillation, heart failure, sudden cardiac death, renal disease and
      ischemic stroke that are the main causes of cardiovascular hospitalization and
      mortality. As obesity and the cardiovascular effects on the vessels and the heart
      start early in life, even from childhood, it is important for health policies to
      prevent obesity very early before the disease manifestation emerge. Key roles in
      the prevention are strategies to increase physical exercise, reduce body weight
      and to prevent or treat hypertension, lipids disorders and diabetes earlier and
      efficiently to prevent cardiovascular complications.Epidemiology and mechanisms
      of obesity-induced hypertension, diabetes and dyslipidemia will be reviewed and
      the role of lifestyle modification and treatment strategies in obesity will be
      updated and analyzed. The best treatment options for people with obesity,
      hypertension, diabetes and dyslipidemia will discussed.

PMID- 29634664
TI  - A novel scoring model for predicting mortality risk in patients with cirrhosis
      and hepatorenal syndrome.
AB  - BACKGROUND AND AIMS: This study aimed to create a risk scoring model for death
      from cirrhosis and hepatorenal syndrome, improve the detection rate of high-risk
      groups, and provide clinical evidence for early intervention treatment. PATIENTS
      AND METHODS: We retrospectively recruited 196 patients with cirrhosis and
      hepatorenal syndrome between 1 January 2013 and 31 July 2014 at Beijing Ditan
      Hospital, Capital Medical University, China. The clinical information,
      biochemical values, age, and sex of the patients were included in the
      multivariate logistic regression model for screening independent risk factors.
      The model was validated in 56 patients with cirrhosis and hepatorenal syndrome
      between 1 August 2014 and 31 December 2014 at Beijing Ditan Hospital, Capital
      Medical University, China. RESULTS: The death risk prediction scoring model
      included the following four independent risk factors: liver cancer, neutrophil
      above 70%, alanine aminotransferase higher than 40 U/l, and creatinine higher
      than 127 mmol/l. The sum death risk score ranged from 0 to 5: 0-2 identified
      patients with a lower risk of death (mortality rates: 12-41.4%), whereas 3-5
      identified patients with a higher risk of death (mortality rates: 48.8-80%).
      Receiver-operating characteristic curves were constructed for the scoring model
      and the areas under the curves (AUC) were compared using the z-test. The AUC of
      the scoring model was 0.843. In addition, the AUC of validated model in 56
      patients was 0.742. CONCLUSION: The scoring model can accurately predict
      mortality risk in patients with hepatorenal syndrome.

PMID- 29634665
TI  - Evaluation of postprandial hypoglycemia in patients with nonalcoholic fatty liver
      disease by oral glucose tolerance testing and continuous glucose monitoring.
AB  - OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) is often associated with
      insulin resistance and glucose intolerance. Postprandial hypoglycemia frequently
      occurs in NAFLD patients; however, the details remain unclear. PATIENTS AND
      METHODS: The 75-g oral glucose tolerance test (75gOGTT) in 502 patients with
      biopsy-proven NAFLD and continuous glucose monitoring (CGM) in 20 patients were
      performed, and the characteristics and causes of postprandial hypoglycemia were
      investigated. RESULTS: The proportion of patients in the Hypo subgroup [plasma
      glucose (PG) at 180 min<fasting-PG (FPG)] among patients with normal glucose
      tolerance was significantly higher than that with diabetes mellitus and impaired
      glucose tolerance or impaired fasting glucose. FPG and hemoglobin A1c (HbA1c)
      were lower, and area under the curve of total insulin secretion within 120 min
      (<120 min) was higher in Hypo than Hyper in overall patients. Although FPG and PG
      at 30 min were higher in Hypo than Hyper, HOMA-IR and the insulinogenic index
      were not different in normal glucose tolerance and impaired glucose tolerance or
      impaired fasting glucose. In multivariate logistic regression analysis, low
      HbA1c, low fasting immunoreactive insulin, and high area under the curve of total
      insulin secretion (<120 min) were found to be independent factors associated with
      hypoglycemia. CGM showed postprandial hypoglycemia until lunch in 70% of NAFLD
      patients. However, no remarkable relationship in terms of hypoglycemia was
      identified between the 75gOGTT and CGM. CONCLUSION: Postprandial hypoglycemia was
      identified in many NAFLD patients detected by 75gOGTT and CGM. It was clarified
      that important causes of postprandial hypoglycemia were related to low HbA1c, an
      early elevation of PG, low fasting and relatively low early insulin secretion,
      and delayed hyperinsulinemia.

PMID- 29634666
TI  - Concurrent extrahepatic autoimmune disorders: unexplored dimension of autoimmune
      liver disease in children.
AB  - BACKGROUND AND AIM: No comprehensive and prospective data are available for
      concurrent extrahepatic autoimmune disorders (CEAIDs) in children with autoimmune
      liver disease (AILD). The aim of this study was to evaluate CEAIDs in AILD and
      their effect on AILD outcome. PATIENTS AND METHODS: Enrolled AILD and CEAIDs
      children were diagnosed on the basis of simplified and standard diagnostic
      criteria, respectively. The clinicopathological profile, treatment response, and
      outcome were compared between AILD with CEAIDs (group A) and AILD without CEAIDs
      (group B). RESULTS: In 62 AILD children, CEAIDs were found in 42% (n=26)
      [vitiligo (42%), celiac disease (CD) (15%), potential CD (15%), autoimmune
      hemolytic anemia (AIHA) (15%)]. CEAIDs were asymptomatic in 75%. Single CEAID was
      found in 81% (21/26) and multiple CEAID was found in 19% (5/26). Significantly
      less biochemical remission (46.1 vs. 74.2%, P=0.03), more treatment failure (23
      vs. 3.2%, P=0.04), and higher mortality (15.3 vs. 3.2%, P=0.04) were encountered
      in group A compared with group B. On multivariate analysis (n=57), less
      biochemical remission in vitiligo (P=0.04); more treatment failure in AIHA
      (P=0.004) and vitiligo (P=0.04); and high mortality in AIHA (P=0.02) subgroups
      were reported. CD treatment has good impact on AILD outcome. All cases of
      diabetes mellitus in AILD were steroid-induced rather than because of
      autoimmunity (absence of antibody against tyrosine phosphatase and glutamic acid
      decarboxylase and elevated C-peptide). CONCLUSION: All AILD children should be
      screened for CEAIDs as the majority are asymptomatic. The AILD outcome was
      favorable in CD, but poor in vitiligo and AIHA. We suggest the incorporation of
      CEAIDs in a pediatric AILD scoring system.

PMID- 29634667
TI  - Experience of Using Shear Wave Elastography Imaging in Superficial Venous
      Insufficiency of the Lower Extremity.
AB  - We investigated the effectiveness of shear wave elastography (SWE) in patients
      with lower extremity superficial venous insufficiency (VI). A total of 138
      symptomatic patients, 51 asymptomatic volunteers, and a total of 359 lower
      extremities (257 symptomatic, 102 asymptomatic) were examined. All participants
      underwent Doppler ultrasound (US) evaluation to determine VI and SWE measurements
      performed by manually drawing vein wall and perivenous tissue with free region of
      interest at the great saphenous vein (GSV) and small saphenous vein (SSV). The
      GSV, SSV diameter, VI, and volume flow of reflux were compared with the SWE
      values. The SWE values of the symptomatic group for GSV and SSV were
      significantly higher than those of the asymptomatic control group regardless of
      whether VI was detected by Doppler US (P < 0.001). There was a statistically
      significant increase in SWE values for the symptomatic group who were diagnosed
      as having reflux in GSV and SSV (P < 0.001). A significant positive correlation
      between increased GSV, SSV diameter, and SWE values was seen (P < 0.001). Venous
      insufficiency can be diagnosed with a 84.7% sensitivity and 84.2% specificity
      when 2655 m/s was designated as cutoff value, and with a 85.4% sensitivity and
      84.2% specificity when 22,350 kPa was designated as the cutoff value in GSV.
      Venous insufficiency can be diagnosed with a 84.3% sensitivity and 82.4%
      specificity when 2845 m/s was designated as cutoff value, and with a 85.7%
      sensitivity and 84.4% specificity when 27,100 kPa was designated as the cutoff
      value in SSV. Shear wave elastography may be used effectively in addition to
      conventional Doppler US examination in diagnosing and following VI.

PMID- 29634668
TI  - Shear Wave Elastography Improves Specificity of Ultrasound for Parotid Nodules.
AB  - OBJECTIVES: This study aimed to determine the performance of Virtual Touch tissue
      quantification (VTQ) technique in the differential evaluation of parotid gland
      nodules. METHODS: Acoustic radiation force impulse VTQ technique was used to
      determine the shear wave velocity (SWV) of 76 patients with parotid nodules and
      30 subjects with normal parotid gland. These nodules were assigned to benign and
      malignant nodules according to histopathology, measurements of SWV were compared,
      a cutoff point for benign and malignant nodules was obtained with reference to
      receiver-operating characteristic curve, and relevant sensitivity and specificity
      were evaluated. RESULTS: There were 61 of 76 patients with benign parotid nodules
      and 15 of 76 patients with malignant nodules. The SWV of the malignant nodules
      was higher than the SWV of the benign nodules, and the SWV of the benign and
      malignant nodules was higher than the normal parotid glands. There were
      significant differences between benign and malignant nodules as well as normal
      parotid glands in terms of the age and SWV of the nodules (all P < 0.001). The
      area under the curve is 0.893, the cutoff is 2.445 m/s, and the sensitivity and
      specificity are 80.0% and 91.8%, respectively. CONCLUSIONS: Acoustic radiation
      force impulse VTQ technique can determine the stiffness of parotid nodules in
      general, its ability to distinct malignant from benign nodular nodule is still
      not strong, and overlay of SWV of VTQ between benign and malignant nodules is the
      main impedance to set cutoff point.

PMID- 29634669
TI  - Effect of Hepatic Inflammation in Chronic Hepatitis C Infection on Fibrosis
      Assessment by Arrival Time Parametric Imaging.
AB  - Arrival time parametric imaging (At-PI) in contrast-enhanced ultrasonography is
      useful for assessing liver fibrosis in chronic hepatitis C (CHC) infection. The
      study aimed to elucidate the effect of hepatic inflammation on At-PI efficiency.
      Subjects were 159 CHC patients who underwent contrast-enhanced ultrasonography
      immediately before liver biopsy. Ultrasound contrast agent was injected, and
      contrast dynamics of the S5 to S6 region of the liver and right kidney were
      recorded for 40 seconds. The At-PI of liver parenchyma blood flow was generated
      using saved video clips. Hepatic blood flow during the first 5 seconds after
      starting contrast injection was displayed in red and that after another 5 seconds
      was displayed in yellow. The ratio of red (ROR) in At-PI images of the entire
      liver was measured with ImageJ. Ratio of red values of livers with different
      activity grades (0-3) were compared for each fibrosis (F) stage as determined by
      biopsy. Correlations of ROR with alanine aminotransferase (ALT) levels were
      analyzed using a linear regression line from the distribution map. Comparison of
      ROR for different activity grades in each F stage revealed no significant
      differences. Correlation coefficient R (P value) for ALT and ROR was R = -0.0094
      (P = 0.43) at F0 to F1, R = -0.186 (P = 0.21) at F2, R = -0.233 (P = 0.27) at F3,
      and R = 0.041 (P = 0.89) at F4, with no significant correlation between ALT and
      ROR in any F stage. Hepatic inflammation in CHC infection does not affect At-PI
      diagnostic accuracy.

PMID- 29634670
TI  - Corneal Stiffness and Its Relationship With Other Corneal Biomechanical and
      Nonbiomechanical Parameters in Myopic Eyes of Chinese Patients.
AB  - PURPOSE: To investigate corneal stiffness and analyze its possible influence on
      other corneal biomechanical and nonbiomechanical parameters in myopic eyes of
      Chinese patients. METHODS: A total of 387 healthy (right) myopic eyes were
      included in this study. Corneal visualization Scheimpflug technology was used to
      measure the corneal stiffness parameter at the first applanation (SP-A1),
      deformation amplitude ratio at 1.0 and at 2.0 mm, biomechanically corrected
      intraocular pressure (bIOP), and corneal deformation parameters during the first
      applanation (A1: A1-time, A1-length, and A1-velocity), second applanation (A2; A2
      time, A2-length, and A2-velocity), and highest concavity (HC; HC-time, HC-radius,
      HC deformation amplitude, and HC peak distance). The Pentacam was used to
      evaluate central corneal thickness, mean corneal curvature (Km), anterior corneal
      central elevation, and corneal asphericity (Q value) of the anterior cornea.
      RESULTS: The mean SP-A1 and bIOP values were 90.46 +/- 15.39 mm Hg/mm and 13.5 +/
      1.85 mm Hg, respectively. The SP-A1 increased with age (beta = 0.41 [95% CI,
      0.28%-0.54%]; P < 0.0001). Corneal stiffness was positively correlated with
      central corneal thickness, uncorrected intraocular pressure, and bIOP and was
      also significantly correlated with all corneal deformation parameters (P < 0.05),
      except A1-length, HC-time, and HC peak distance. Corneal stiffness was negatively
      correlated with central corneal elevation of the anterior surface (r = -0.124, P
      = 0.014) and mean corneal curvature (r = -0.114, P = 0.025) and positively
      correlated with the Q value of the anterior surface (r = 0.109, P = 0.032).
      CONCLUSIONS: Corneal stiffness increased with age. Stronger corneal stiffness may
      be related to flattening of the cornea and higher intraocular pressure.

PMID- 29634671
TI  - Measuring Endothelial Cell Loss on DMEK Grafts After Transplantation in Human
      Cadaveric Whole Eyes: Description of the Technique and Pilot Study.
AB  - PURPOSE: To describe a novel method for analyzing Descemet membrane endothelial
      keratoplasty (DMEK) graft damage after implantation into human cadaveric donor
      eyes and to compare results achieved by performing DMEK with a surgeon's long
      established technique compared with those of an unfamiliar technique. METHODS:
      Eight DMEK grafts were implanted into previously frozen human cadaveric eyes.
      Four grafts were implanted using a Straiko injector and tap technique familiar to
      the surgeon (C.S.S., 3-yr experience), and 4 grafts were implanted using the Tan
      EndoGlide and "donor mat device" pull-through technique new to the surgeon. After
      implanting a DMEK graft and attaching it to the recipient stroma with an air
      bubble tamponade, the corneoscleral cap was "recovered" from the cadaveric globe
      using standard techniques. The DMEK graft was stained with Calcein-AM. After
      staining, a 9.5-mm stromal "carrier button" was punched, and the carrier and
      graft were transferred to a microscope slide. Grafts were imaged and analyzed
      using FIJI trainable segmentation. RESULTS: Donor graft characteristics were
      similar between both groups. Grafts implanted using the surgeon's routine
      technique showed an average endothelial cell loss (ECL) of 31% +/- 4% (n = 3).
      Grafts implanted using the technique unfamiliar to the surgeon showed an average
      ECL of 47% +/- 24%, but with a trend toward improvement (1 = 76%, 2 = 65%, 3 =
      32%, 4 = 17% ECL). CONCLUSIONS: Our proof-of-principle experiment shows that this
      imaging approach enables quantification of ECL caused by different instruments
      and surgical techniques after graft implantation. We have used this method to
      visualize the learning curve of 1 surgeon when learning a new surgical technique.

PMID- 29634672
TI  - Experimental Evidence of the Healing Properties of Lactobionic Acid for Ocular
      Surface Disease.
AB  - PURPOSE: The aim of this study was to investigate the properties of lactobionic
      acid (LA) as a possible supplement in artificial tears in in vitro and in vivo
      experimental model systems. LA is a bionic derivative of a polyhydroxy acid,
      which consists of one galactose attached by an ether link to a gluconic acid. It
      is a molecule endowed with several properties that make it an ideal supplement in
      artificial tears: it is highly hygroscopic and a powerful antioxidant, it is an
      iron chelator and inhibits matrix metalloprotease activity; it favors wound
      healing (WH); and it inhibits bacterial growth. METHODS: Promotion of WH by LA,
      alone or in combination with hyaluronic acid (HA), was investigated in vitro on
      monolayers of rabbit corneal cells (Statens Seruminstitut) and in vivo after
      epithelium debridement of rabbit corneas. TGF-beta expression and MMP-9 activity
      in wounded corneas were detected in tears and cornea extracts by western blot or
      by Enzyme Linked ImmunoSorbent Assay (ELISA). Bacterial growth inhibition by LA
      was checked on Staphylococcus aureus isolates in liquid culture. RESULTS: LA,
      with or without HA, favors WH in vitro and in vivo. The WH assay on the rabbit
      cornea showed that 4% LA in association with 0.15% HA also resulted in a blunted
      increase of MMP-9 and TGF-beta in tears and corneal tissue. Finally, the presence
      of 4% LA resulted in slower growth of cultured bacterial isolates. CONCLUSIONS:
      Our findings support the hypothesis that LA could be a useful supplement to
      artificial tears to treat ocular surface dysfunction such as dry eye.

PMID- 29634673
TI  - Double-Bubble Technique in Descemet Membrane Endothelial Keratoplasty for
      Vitrectomized Eyes: A Case Series.
AB  - PURPOSE: To describe a modified technique for Descemet membrane endothelial
      keratoplasty (DMEK) in vitrectomized eyes that had undergone transscleral-sutured
      intraocular lens (IOL) implantation (IOL-suture) and pars plana vitrectomy.
      METHODS: This was a prospective interventional case series. Patients exhibiting
      endothelial dysfunction with aphakia, or dislocated IOLs, who underwent IOL
      suture and pars plana vitrectomy, were enrolled. Patients underwent DMEK using
      the "double-bubble technique," which is characterized by the placement of 2
      bubbles, 1 above and 1 beneath the graft. One small air bubble is placed over the
      graft for the purpose of unfolding the graft; the other large bubble is injected
      under the graft to enable fixation of the graft. Best spectacle-corrected visual
      acuity, central corneal thickness, endothelial cell density, the time of graft
      unfolding (using a surgical video), and the incidence of
      intraoperative/postoperative complications were analyzed. RESULTS: This study
      included 6 eyes of 6 patients (3 men and 3 women; mean age 78.0 +/- 2.5 years).
      Although the unfolding time was relatively long (10.1 +/- 4.5 minutes), all
      surgeries were uneventful. Rebubbling was required in 1 eye (16.6%). Best
      spectacle-corrected visual acuity improved significantly in all eyes. There was
      no primary graft failure. CONCLUSIONS: This technique (double bubble technique)
      enables safe and easy DMEK surgery, even in eyes that have been previously
      vitrectomized and IOL-sutured. Further clinical studies with a large number of
      patients exhibiting complex eyes are required to definitively establish the
      clinical value of this technique.

PMID- 29634674
TI  - Designing Minimally Invasive Preocular Contact Tips for Potential Application in
      Tear Collection.
AB  - PURPOSE: Basal tear fluid has drawn great attention as a medium for many disease
      markers and, hence, for its potential to be used in self-diagnosis. However,
      collection of basal tear fluid is difficult because a conventional tear
      collector, such as a glass capillary tube, may inflict irritation or damage on
      the sensitive ocular surface. Therefore, we sought to design a tip for contact
      with the preocular surface [a preocular contact tip (PCT)] that minimizes damage
      to the ocular surface. METHODS: We designed the shape of the tip to have rounded
      boundaries and no sharp edges. We then tested different tip areas, each of which
      was contacted with the inferior palpebral conjunctiva of rabbit eyes at varying
      depths to demonstrate their feasibility in vivo. The area of damaged tissue and
      the time required for tissue recovery were monitored according to the pressure
      applied through the tips. RESULTS: Our findings revealed that a contact area of
      the PCT greater than 2.36 mm caused relatively little damage to the inferior
      palpebral conjunctival tissue, which could recover within 4 hours after contact
      at all pressing depths. In contrast, a glass capillary tube caused relatively
      severe damage, which did not recover for more than 8 hours. The PCT (3.14 mm) was
      embedded with a microchannel as a prototype tear collector, which could collect
      0.3 MUL of tears with minimal tissue damage. CONCLUSIONS: The PCT proposed in
      this study can be a promising tool for minimally invasive collection of basal
      tears from the inferior palpebral conjunctiva.

PMID- 29634675
TI  - Overview of Systemic Candida Infections in Hospital Settings and Report of
      Candida After DMEK Successfully Treated With Antifungals and Partial Graft
      Excision.
AB  - PURPOSE: To report novel surgical and medical management of intraocular and
      corneal infection with Candida glabrata that manifested 3 months after Descemet
      membrane endothelial keratoplasty (DMEK) and to review demographic reasons for
      increasing fungal contamination of donor tissue. METHODS: Demographics, donor rim
      cultures, diagnostic tests, management, clinical course, outcomes, and donor mate
      outcomes are reported for a fungal infection after DMEK. RESULTS: The fungal
      infection was treated for 3 weeks with a combination of intracameral and
      intracorneal voriconazole and intracameral and topical amphotericin B (off-label
      use). After initial improvement, the infection appeared to spread to the
      posterior chamber and the cornea decompensated. Pars plana vitrectomy was
      performed, and the fungal plaque and underlying area of the graft (approximately
      3 mm area) were excised with the vitrector. After surgical intervention, the
      voriconazole and amphotericin B injections were discontinued, and oral
      posaconazole was prescribed for 2 months (off-label use). This combination of
      surgical and medical management successfully cleared the infection. Surprisingly,
      corneal edema completely resolved, and central DMEK endothelial cell density was
      2506 cells/mm 1 month after discontinuing the antifungal injections, which
      apparently caused reversible endothelial toxicity. CONCLUSIONS: The incidence of
      nosocomial fungal infections, particularly non-albicans Candida, is increasing,
      as are the rates of positive fungal cultures from corneal donor tissue and
      postkeratoplasty fungal infections. Prospective studies are needed to assess the
      value of routine donor cultures, compare the safety and efficacy of various
      prophylactic treatments, and evaluate addition of antifungals to cold storage
      media.

PMID- 29634676
TI  - Simulation Model for DMEK Donor Preparation.
AB  - PURPOSE: To demonstrate a simulation model for donor preparation in Descemet
      membrane endothelial keratoplasty (DMEK). METHODS: The inner transparent membrane
      of the onion (Allium cepa) was used as a simulation model for human Descemet
      membrane (DM). Surgical video (see Video, Supplemental Digital Content 1,
      http://links.lww.com/ICO/A663) demonstrating all the steps was recorded. RESULTS:
      This model closely simulates human DM and helps DMEK surgeons learn the nuances
      of DM donor preparation steps with ease. The technique is repeatable, and the
      model is cost-effective. CONCLUSIONS: The described simulation model can assist
      surgeons and eye bank technicians to learn steps in donor preparation in DMEK.

PMID- 29634677
TI  - EASTERN ASSOCIATION FOR THE SURGETY OF TRAUMA SCOTT B. FRAME, MD MEMORIAL
      LECTURE: "THE POVERTY OF THEORY: EVIDENCE-BASED MEDICINE AND THE SOCIAL
      CONTRACT".

PMID- 29634678
TI  - Percutaneous Balloon Kyphoplasty Vertebral Augmentation for Compression Fracture
      Due to Vertebral Metastasis: A 12-Month Retrospective Clinical Study in 72
      Patients.
AB  - BACKGROUND Vertebral compression fracture is common in osteoporosis, but can also
      occur due to bone metastases, for which current treatment options are limited and
      include bone-strengthening with cement and supportive care. Kyphoplasty is a
      surgical method of bone augmentation that can reduce pain, stabilize vertebral
      bone, and restore some or all of the vertebral body height. The aim of this study
      was to investigate the clinical results of balloon kyphoplasty in the correction
      of vertebral deformity due to metastatic vertebral compression fracture. MATERIAL
      AND METHODS A retrospective clinical study included 72 patients (82 vertebral
      bodies) with metastases resulting in vertebral compression fracture, treated by
      percutaneous balloon kyphoplasty; 9 patients were found incidentally to have
      vertebral metastases. Bone mineral density (BMD) levels were measured. Patient
      responses from questionnaires, including the visual analog scale (VAS) for pain
      intensity, and the Oswestry Disability Index (ODI) for disability, were scored.
      The local kyphosis angle (KA) and the vertebral height ratio (VHR) were measured.
      All patients were followed up for 12 months. The initial postoperative and 12
      month postoperative values, and the preoperative and postoperative values were
      compared. RESULTS Following balloon kyphoplasty, the KA, VHR, VAS, and ODI scores
      significantly improved at the final 12-month follow-up compared with preoperative
      levels (p<0.05, and p<0.001). There was cement leakage in 6 procedures (8.3%) and
      adjacent segment fracture in 11 procedures (15.2%). CONCLUSIONS Balloon
      kyphoplasty was an effective method to reduce pain, reduce disability, and
      improve quality of life by eliminating kyphotic deformity in pathological
      vertebral compression fractures due to vertebral metastases.

PMID- 29634679
TI  - A new site of attack for a malaria vaccine.

PMID- 29634680
TI  - Erratum: The molecular landscape of pediatric acute myeloid leukemia reveals
      recurrent structural alterations and age-specific mutational interactions.
AB  - This corrects the article DOI: 10.1038/nm.4439.

PMID- 29634681
TI  - Predicting leukemia relapse.

PMID- 29634683
TI  - Corrigendum: Colonic organoids derived from human induced pluripotent stem cells
      for modeling colorectal cancer and drug testing.
AB  - This corrects the article DOI: 10.1038/nm.4355.

PMID- 29634684
TI  - Corrigendum: Sex-specific transcriptional signatures in human depression.
AB  - This corrects the article DOI: 10.1038/nm.4386.

PMID- 29634682
TI  - Current understanding of the human microbiome.
AB  - Our understanding of the link between the human microbiome and disease, including
      obesity, inflammatory bowel disease, arthritis and autism, is rapidly expanding.
      Improvements in the throughput and accuracy of DNA sequencing of the genomes of
      microbial communities that are associated with human samples, complemented by
      analysis of transcriptomes, proteomes, metabolomes and immunomes and by
      mechanistic experiments in model systems, have vastly improved our ability to
      understand the structure and function of the microbiome in both diseased and
      healthy states. However, many challenges remain. In this review, we focus on
      studies in humans to describe these challenges and propose strategies that
      leverage existing knowledge to move rapidly from correlation to causation and
      ultimately to translation into therapies.

PMID- 29634686
TI  - A molecular mechanism governing memory precision.

PMID- 29634685
TI  - Corrigendum: Genetic identification of thiosulfate sulfurtransferase as an
      adipocyte-expressed antidiabetic target in mice selected for leanness.
AB  - This corrects the article DOI: 10.1038/nm.4115.

PMID- 29634687
TI  - Inflammation weakens HIV prevention.

PMID- 29634688
TI  - Corrigendum: Positively selected enhancer elements endow osteosarcoma cells with
      metastatic competence.
AB  - This corrects the article DOI: 10.1038/nm.4475.

PMID- 29634690
TI  - Transplanted neural progenitors bridge gaps to benefit cord-injured monkeys.

PMID- 29634691
TI  - Experimenting with blockchain: Can one technology boost both data integrity and
      patients' pocketbooks?

PMID- 29634692
TI  - Corrigendum: Classification and characterization of microsatellite instability
      across 18 cancer types.
AB  - This corrects the article DOI: 10.1038/nm.4191.

PMID- 29634689
TI  - Erratum: Sorafenib promotes graft-versus-leukemia activity in mice and humans
      through IL-15 production in FLT3-ITD-mutant leukemia cells.
AB  - This corrects the article DOI: 10.1038/nm.4484.

PMID- 29634693
TI  - Catalyzing the field of precision oncology, one basket at a time.

PMID- 29634694
TI  - A tale of two diseases: Aging HIV patients inspire a closer look at Alzheimer's
      disease.

PMID- 29634696
TI  - A checkup for the flu vaccine.

PMID- 29634695
TI  - Corrigendum: Suppression of luteinizing hormone enhances HSC recovery after
      hematopoietic injury.
AB  - This corrects the article DOI: 10.1038/nm.4470.

PMID- 29634697
TI  - Sustainable Developmental Goals (SDGs) and Eye Health Care in Nepal.
AB  - In 2015, the United Nations (UN) adopted the resolution of transforming our world
      by the year 2030 through the agenda of Sustainable Development with a primary
      focus on strengthening universal peace with larger freedom [United Nations 2015,
      Griggs D 2012]. All member countries including Nepal agreed to this ambitious
      plan for relieving poverty and reducing global inequality over a span of 15 years
      starting from 2016 to 2030. All the health programs including, Millennium
      Developmental Goals, universal eye health or Vision 2020 - the elimination of
      avoidable blindness by 2020 are expected to thrive under the umbrella of
      Sustainable Development Goals (SDGs). There are 17 goals and 169 targets. The
      three dimensions of sustainable development - economical, social and
      environmental - are balanced in this new initiative [eye health Australia 2015].
      The overall effect of this initiative will be beneficial to human beings and our
      planet with human health as one facet among many. All efforts would be directed
      to review, realign and integrate the ongoing public health activities to attain
      SGDs [World Health Organization 2016].

PMID- 29634698
TI  - Pursuit Of An Ideal Model For Community Eye Health - Non-Governmental
      Organisations (NGOs).
AB  - Visual impairment is a crippling condition affecting quality of life and
      depriving patients of many opportunities. It is associated with increased
      mortality rates directly through occurrence of adverse events such as falls and
      impaired emotional well-being, and indirectly through visual impairment brought
      upon by systemic conditions such as diabetes and hypertension (Foong et al. 2008,
      Fong et al. 2014, Khanna et al. 2013, Song et al.2014, Wang et al. 1999). The
      number of patients suffering from reversible causes of blindness is substantial.
      In 2010, World Health Organisation estimates that 285 million (4.25%) of the
      world's population is visually impaired, of which 39 million (14%) are blind.
      Approximately, 80% of the visual impairment is preventable. Notable causes of
      preventable blindness include cataracts (51%), glaucoma (8%), age-related macular
      degeneration (5%), corneal opacities (4%), trachoma (3%) and uncorrected
      refractive errors (3%) (WHO, 2015). These conditions can be easily diagnosed and
      treated by ophthalmologists if adequate resources are available. It is
      increasingly challenging for the ophthalmologists and current healthcare systems
      to meet the ever-expanding demands of patients with reversible causes of
      blindness.

PMID- 29634699
TI  - Incidence and risk factors of retinopathy of prematurity in Western India -
      Report from A Regional Institute of Ophthalmology.
AB  - INTRODUCTION: Retinopathy of prematurity is an important cause of childhood
      blindness amongst premature babies in developing as well as developed world.
      OBJECTIVES: To report the incidence and risk factors of ROP from a regional
      institute of Ophthalmology in western India and compare it with the existing
      scenario. MATERIALS AND METHODS: This was prospective observational study of
      babies born at <34 weeks of gestational and/or <1700 grams birth weight between
      January 2012 and October 2013. Birth related information viz. O2 administration
      was recorded in consultation with a neonatologist and babies were evaluated for
      the presence of ROP. Multivariable logistic regression was used to identify risk
      factors for any-ROP and severe-ROP requiring treatment. RESULTS: Out of 280
      babies screened, any-ROP was seen 54 babies(19.28%) out of which, severe-ROP was
      found in 28 babies(10.29%).Likelihood of developing any-ROP increased 3 fold
      (95%CI=1.1 - 6.5), and severe-ROP by 7 fold (95%CI=1.6 - 27.5), if oxygen therapy
      as administered. Older gestational age was associated with reduced likelihood of
      developing severe-ROP (Odds ratio=0.79, 95%CI=0.6 - 0.9) but not any-ROP. Twenty
      four babies (86%) with severe ROP responded well to laser or Bevacizumab therapy
      while 4 babies developed retinal detachment. CONCLUSION: This is the first report
      quoting only incidence and risk factors of ROP from western India. One in 5
      babies develop any-ROP similar to that reported across rest of the country. The
      incidence of severe-ROP requiring treatment appears to be marginally higher, and
      treatment outcomes in these eyes are similar to that reported in literature.

PMID- 29634700
TI  - Learning Curve in External DCR - A Trainee's Perspective.
AB  - PURPOSE: The aim of this study is to determine the success rate over time in
      patients undergoing External Dacryocystorhinostomy (DCR) with acquired naso
      lacrimal duct obstruction (NLDO), when done by a trainee ophthalmologist.
      METHODS: The study was Prospective Observational study and was conducted in
      Tertiary Eye Hospital, Uttar Pradesh, India. One hundred and fourteen consecutive
      adult patients underwent external DCR for acquired complete NLDO by a trainee
      with less than 3 years of experience in ophthalmology between November 2011 and
      March 2013. Postoperative anatomic success rate was determined at 6 months on the
      basis of the patency of lacrimal sac syringing and patients were asked to
      subjectively evaluate improvement of their epiphora using a questionnaire.
      RESULTS: Anatomical success rate across the entire study period was 93.7% and
      this improved from 87% in the first tertile of 38 patients to 94% in the second
      tertile and 100% in the final tertile of cases (p<0.05). Overall complication
      rate was 16.67% and reduced from 29% in the first tertile to 8% in the final
      tertile (p<0.05). Loss of anterior nasal flap was the commonest complication (10
      cases) during the training period. CONCLUSION: External DCR, as a primary
      procedure for acquired NLDO, even when operated by trainee ophthalmologists, has
      a relatively high success rate that improves over time. As the learning curve
      improves, complication rates reduce significantly. FINANCIAL DISCLOSURE: No
      author has any financial or proprietary interest in the material or method
      mentioned.

PMID- 29634701
TI  - Tacrolimus versus Cyclosporine- Comparative Evaluation as First line drug in
      Vernal keratoconjuctivitis.
AB  - INTRODUCTION: The aim of the study was to evaluate and compare the efficacy, side
      effects and recurrence rate of vernal kerato conjunctivitis (VKC) with 0.03%
      tacrolimus and 0.05% cyclosporin. MATERIAL AND METHOD: A prospective randomised
      double blinded comparative study was conducted at a tertiary eye center. 46
      Patients of VKC between March 2015- August 2015 were randomly divided into two
      groups and treated for 6weeks with either Tacrolimus(0.03%) eye ointment BD or
      Cyclosporine (0.05%) eyedrops QID.The main outcome measures were scoring and
      comparison of Total subjective symptom scores (TSSS) and Total objective ocular
      sign scores (TOSS) within and between the Groups at each follow up.Thirty two
      patients, sixteen from each group, with comparable baseline characters were
      analysed. RESULTS: With treatment both TSSS and TOSS decreased consistently in
      both groups without any adverse effects but an increase in scores was noticed
      within two weeks after drug withdrawal. CONCLUSION: Both drugs are equally
      effective and safe in VKC but with short lasting effect.

PMID- 29634702
TI  - Prevalence of diabetic retinopathy among self-reported adult diabetics in
      districts of Eastern Nepal in a community based study.
AB  - INTRODUCTION: Diabetic retinopathy (DR) is the leading cause of blindness among
      working age adults around the world. Each year more and more people live with
      this condition, which can result in life-changing complications. OBJECTIVE: To
      determine the prevalence and risk factors of diabetic retinopathy (DR) in a large
      community based screening programme, in order to estimate the future burden of
      the disease. MATERIALS AND METHODS: A cross sectional community based study was
      conducted between 1st January and 31st December 2014 in a purposive sample of
      adults with selfreported diabetes mellitus (DM) from Morang and Sunsari district
      of Nepal. A structured questionnaire was used to collect patient data.
      Ophthalmological evaluation was done and fundus was examined for grading DR using
      direct and indirect ophthalmoscope. RESULTS: Among the 698 diabetic patients,
      mean age was 55.02+/-11.8 years (ranging from 24 to 91 years). 12.3% of diabetic
      were not under any treatment. Only 69.3% of patients had visited eye specialist
      for diabetic retinopathy screening. Prevalence of DR was found to be 15.3%; 13.9%
      had non-proliferative DR and 1.4% had proliferative DR. Prevalence of diabetic
      macular edema was 2.1%. In Morang district prevalence of DR was 14.2% and in
      Sunsari district it was 16.2%. In the binary-logistic regression analysis,
      duration of diabetes was associated with significantly increased risk of DR (OR:
      1.13; 95% confidence interval (CI), 1.09 to 1.17; p<0.001). History of absence of
      arterial hypertension decreased the risk of DR (OR: 0.56; 95% CI, 0.36 to 0.87;
      p=0.01). CONCLUSION: One sixth of the patients with diabetes in the Eastern
      region of Nepal have retinopathy. Diabetic retinopathy risk increased with
      duration of diabetes and decreased with history of no co-existing arterial
      hypertension.

PMID- 29634703
TI  - Factors affecting the visual outcome of pediatric cataract surgery: a hospital
      based prospective study in eastern Nepal.
AB  - The World Health Organization's (WHO) global initiative for the elimination of
      avoidable blindness by the year 2020 (Thylefors et al., 1995) has prioritized the
      control of childhood blindness. Currently cataract remains one of the most
      important causes of treatable blindness in children (Giles et al., 2016). In
      Nepal, as in other developing countries, cataract is believed to be a leading
      cause of blindness in children. According to The Nepal Blindness Survey from 1978
      to 1980, congenital cataract accounted for 16.3% of blindness detected in
      children under the age of 15 years (Brilliant et al., 1985). Epidemiology of
      Blindness in Nepal 2012 survey has suggested that the prevalence of childhood
      blindness has reduced from 0.68% in 1981 to 0.4% in 2011 (Sapkota, 2012).

PMID- 29634704
TI  - Incidence of primary peripheral posterior capsular opacification after cataract
      surgery and posterior capsular opacification in the patients implanted with
      foldable intraocular lenses.
AB  - INTRODUCTION: Preexisting posterior capsular opacification is commonly seen in
      the developing world due to late presentation of patients for cataract surgery.
      Patients are implanted with either hydrophilic or hydrophobic IOL. Effect of
      these IOLs on pre-existing posterior capsular opacification has not yet been
      reported. AIM: To determine the incidence of peripheral preexisting posterior
      capsular opacity (PPPCO) in patients undergoing cataract surgery and the rate of
      posterior capsular opacification (PCO) following implantation of hydrophilic and
      hydrophobic intraocular lens (IOLs). STUDY DESIGN: Prospective, observational
      case study Setting: Tertiary eye care center in central India. METHODOLOGY: 1400
      consecutive patients undergoing phacoemulsification of senile cataract between
      July 2009 and June 2010 discovered to have PPPCO were included in the analysis.
      Patients were either implanted with hydrophilic (n= 40) or hydrophobic IOL
      (n=40). Images of the posterior capsule immediately and 3-years postoperatively
      were compared. Patients were followed up for development of PCO, visual outcome
      at 3 years and neodymium: YAG laser posterior capsulotomy (NYLPC) rate. RESULTS:
      Eighty patients were found to have PPPCO (incidence of 5.7%). 47.5% of PPPCOs
      were from mature senile cataracts (n = 38), 36.2% were from posterior subcapsular
      cataracts (n = 29) and 16.2% were from posterior polar cataracts (n = 13). NYLPC
      was performed in 9 patients receiving hydrophilic (22.5%) and 3 patients
      receiving hydrophobic IOLs (7.5%; p = 0.12). Average time to NYLPC was 18 months
      in the hydrophilic and 30 months in the hydrophobic group (p = 0.002). Visual
      outcome was satisfactory at 3-years of follow-up. CONCLUSION: PPPCO is a frequent
      occurrence in mature cataract and there is a higher incidence of PCO in PPPCO
      patients implanted with hydrophilic IOL than with hydrophobic IOL. Therefore,
      hydrophobic IOL should be considered for patients discovered to have PPPCO during
      cataract removal.

PMID- 29634706
TI  - Conjunctival Lesions: When Should We Perform Biopsy?
AB  - INTRODUCTION: The conjunctiva is a thin and flexible mucus membrane that provides
      a protective barrier for the eye. Very few histopathologic studies have been
      conducted on biopsies from conjunctival lesions (CL) in central India. OBJECTIVE:
      To study the spectrum of CL and define those lesions that need attention with
      regard to need of biopsy in order to prevent grave sequelae and ocular morbidity.
      RESULTS: Degenerative conditions such as pterygium followed by pinguicula were
      the commonest lesions seen in conjunctiva. Out of 129 subjects, youngest in the
      series was 3 years old while oldest patient was 72 years of age. Commonest age
      interval for involvement was 35 to 50 years. In children below 8 years, cystic
      lesions (infective or inclusion), limbal dermoid and choristoma were seen.
      Vascular lesions were noticed by patients for the first time between mid-teens to
      25 years age. Premalignant lesions were dysplasia, actinic keratosis and PAM with
      or without XP. Malignant lesions in this series were squamous cell carcinoma,
      basal cell carcinoma and sebaceous carcinoma; which were observed in the age
      interval 25 to 75 years. In none of the malignant conditions there was deeper
      penetration into the globe or orbit. Though diagnosed within two weeks duration
      (by incisional biopsy) from appearance of nodule, unfavourable outcome was seen
      only in one malignant CL; a case having sebaceous carcinoma. In all pediatric
      cases outcome was good, except in child having choristoma, where amblyopia ensued
      before a diagnosis was made. Response to sclerotherapy was excellent as all the
      epibulbar vascular malformations regressed. All degenerative lesions regressed
      except one recurrence in a recurred pterygium. Case diagnosed as large B cell
      lymphoma recurred after one year. Dysplastic changes were seen to occur at limbus
      on followup in one XP, but in all cases of naevi, neither cellular atypia was
      seen nor melanoma developed. CONCLUSION: An overview of various CL disclosed that
      clinician has to differentiate benign from premalignant and malignant lesions.
      Early diagnosis, proper histological study and patient education, all are equally
      important for achieving good outcome.

PMID- 29634705
TI  - Co morbidities among cataract- operated patients in Rural Nepal.
AB  - INTRODUCTION: Himalaya Eye Hospital (HEH), established in 1993, is providing eye
      care services in Gandaki, Dhaulagiri and Karnali zones. It has been providing
      surgical and nonsurgical eye camps in rural areas of Gandaki, Dhaulagiri and
      Karnali zones. The aim of this study was to determine the prevalence of ocular
      and systemic co morbidities among the persons treated in rural Asian setting.
      METHOD: This is the prospective non-interventional study. Patients who came to
      take services in surgical eye camp in rural area of Nepal were included. Data
      were collected by interviewing the patients. They were interviewed by local
      volunteers with he questionnaires prepared in English language. The volunteers
      were explained about the medical terminology and they interviewed the patients in
      native language. RESULT: Out of 675 patients 401(59%) had systemic co
      morbidities. Back pain and arthritis being the most common with 321(48%) and
      260(38%) respectively. CONCLUSION: This study shows the systemic co morbidities
      among the patients who came to seek ocular treatment in eye camp in rural area of
      Nepal. We should do this kind of studies in different area of Nepal. These kinds
      of study give us total burden of systemic morbidity and help to treat
      accordingly.

PMID- 29634707
TI  - Scleritis and Takayasu's disease - rare combined presentation.
AB  - INTRODUCTION: Takayasu's disease (TD) (pulseless disease, aortic arch syndrome)
      is a rare but potentially life-threatening chronic giant cell vasculitis. The
      major complications attributed to the disease include Takayasu's retinopathy,
      secondary hypertension, aortic regurgitation, and arterial aneurysm. The aim of
      this study is to describe a patient with Takayasu's disease and scleritis and to
      show its association. CASE REPORT: We describe a 44-year-old female patient with
      Takayasu's disease who presented with bilateral anterior scleritis in the form of
      painful red eye. Patient did not have any associated autoimmune diseases. Patient
      was diagnosed to have TD and was treated with immunosuppressant. CONCLUSION:
      Scleritis though rare can be a vasculitic feature of TD. This is a first report
      of Takayasu's disease with scleritis, which has been documented in Nepal.

PMID- 29634708
TI  - Chronic blepharitis like picture in patients with Discoid lupus erythematosis -
      Case series.
AB  - BACKGROUND: Blepharitis is a very common condition encountered in ophthalmology
      outpatient care department. Dermatological diseases like seborrheic keratopathy
      and rosacea have been frequently discussed as being associated with blepharitis.
      However Discoid lupus erythematosis [DLE], an autoimmune condition has only
      rarely been reported to involve the eyelids mimicking blepharitis. DLE affecting
      the eyelids can produce significant morbidity with lid deformities, trichiasis
      and symblepharon if left untreated. OBJECTIVE: To report three consecutive cases
      of DLE with eyelid lesions mimicking blepharitis. They presented to the
      department of ophthalmology at our institute from April 2014 to March 2016. The
      first case presented with involvement of lower eyelid in one eye. She was having
      multiple skin lesions which on biopsy confirmed the diagnosis of DLE. The second
      case was a diagnosed case of DLE who received treatment 4 years back and came
      with relapse of the disease affecting the eyelid. The third case was a recently
      biopsy confirmed case of DLE with multiple skin lesions along with bilateral
      eyelid involvement. Two of them had madarosis and one case had destruction of the
      outer lid margin at presentation. All three cases responded well to treatment
      with Hydrxychloroquin. CONCLUSION: The discoid lesions of DLE affecting the
      eyelids can mimic the appearance of chronic blepharitis. Ophthalmologists should
      be aware that DLE is a possibility while dealing with an atypical case of chronic
      blepharitis. Early diagnosis and treatment can prevent deformities of eyelid.

PMID- 29634709
TI  - Lymphoma Maxilla mimicking orbital cellulitis; case report and review of
      Literature.
AB  - BACKGROUND: Sinonasal lymphomas are the commonest nonepithelial malignancies of
      the nasal cavity and paranasal sinuses. They may spread from their site of origin
      in nasal cavity and invade adjacent structures including orbits leading to
      varying presentation and a diagnostic dilemma. CASE: A-77- year old Nepalese male
      presented with swelling of left eye since 1 month and pain in the same eye since
      2 days. OBSERVATION: Examination revealed axial proptosis, swelling of lids,
      restricted extraocular movement, diffuse conjunctival and ciliary congestion with
      chemosis. Visual acuity was grossly decreased. The case was diagnosed as left
      orbital cellulitis and treated with broad spectrum intravenous antibiotics and
      oral steriods. There was no response despite 3 days of antibiotics and steroids
      therefore a computed tomography was planned which showed features of Sinonasal
      malignancy invading the orbit. Repeated biopsy was suggestive of malignant small
      round cell tumour. In the view of unclear preoperative biopsy indicating further
      details on the histologic type of tumor and extensive erosion of maxilla with
      complete loss of vision in the eye the patient was planned for Total Maxillectomy
      with Orbital extenteration of the left orbit. Post-operative histopathological
      and Immunohistochemical report were suggestive of High grade Lymphoma. The
      patient was advised for Adjuvant Chemotherapy and Radiotherapy, which the patient
      refused due to financial constraints. He is on occasional follow up since the
      last 6 months. CONCLUSIONS: The diagnosis of maxillary sinus lymphoma needs to be
      borne in mind when a clinician encounters a case of Orbital Cellulitis. It may be
      difficult to diagnose clinically and require radio-pathological correlation.

PMID- 29634710
TI  - Nocardia choroidal abscess-a Case report with Review of literature.
AB  - INTRODUCTION: Nocardia is a common cause of corneal infections but is a rare
      cause of choroidal abscess. We report a rare case of choroidal abscess, secondary
      to Nocardia and its management. CASE: We report a case of choroidal abscess
      secondary to Nocardia asteroides species in an immunocompetent young male
      diagnosed by culture positivity of vitreous biopsy. He was managed by oral
      trimethoprimsulfamethoxazole and intravitreal Amikacin injections. CONCLUSION:
      All the previous reported cases were found to be immunocompromised patients.
      However, our patient was immunocompetent and the confirmation of diagnosis was
      done by culture of vitreous biopsy in comparison to a retinochoroidal biopsy, in
      all other previous cases.

PMID- 29634711
TI  - Pigmented free floating vitreous cyst in a 10 years old child.
AB  - Pigmented free-floating vitreous cyst in retrolental space is rare. It can
      represent its congenital origin after spontaneous detachment from the ciliary
      body epithelium or after trivial injury. We report a case of pigmented, free
      floating non-infective vitreous cyst in a 10 year old child who presented with
      compliant of transient blurring of vision three days after she joined swimming
      class. A thorough eye examination with ultrasound B scan and ultrasound
      biomicroscopy was done to rule out any other associated conditions.

PMID- 29634712
TI  - Ocular Decompression Retinopathy : A Case Series.
AB  - INTRODUCTION: Ocular decompression retinopathy (ODR) is a relatively rare entity
      with variable prognosis depending on extent and pre-existing condition. This
      article describes profile of two cases with a brief review of the condition. CASE
      REPORT: Case 1 highlights extensive choroidal detachment with subhyaloid
      haemorrhage and multiple intra-retinal hemorrhages in the posterior pole seen on
      first post-operative day in a 6 year old child with congenital glaucoma who
      underwent Trab & Trab. Case 2 describes multiple intraretinal hemorrhages seen at
      posterior pole on second post-operative day in a 24 year old pregnant lady with
      post traumatic cataract and secondary glaucoma who underwent cataract extraction
      with Cionni ring. Both patients had complete resolution of the haemorrhages with
      topical steroids. CONCLUSION: Ocular decompression retinopathy is mostly seen
      after operations on cases with advanced glaucoma and those with vulnerable blood
      flow fluidics. Adequate precautions to prevent this entity should be adopted
      during surgery and management of the manifest entity is conservative with good
      prognosis.

PMID- 29634713
TI  - Spontaneous formation and closure of full thickness macular hole in a vitrecto
      mised eye : a case report.
AB  - The exact pathogenesis of macular hole (MH) is controversial with most of the
      cases being idiopathic. Trauma is an important cause of secondary MH formation.
      MH post Pars Plana Vitrectomy (PPV) is an even rare entity with only a handful of
      cases reported so far ( Kumagai et al, 2008; Smiddy W.E, 1993; Kimura et al,
      2005). An even rarer event is spontaneous closure of post PPV full thickness
      macular hole (FTMH), though spontaneous closure of traumatic macular hole (TMH)
      has been reported before. Herein, we report a 26 year old male patient who
      developed FTMH post PPV that closed spontaneously.

PMID- 29634714
TI  - Usher syndrome Type I in an adult Nepalese male: a rare case report.
AB  - Usher syndrome, also known as retinitis pigmentosa-dysacusis syndrome, is an
      extremely rare genetic disorder, characterized by retinitis pigmentosa (RP) and
      congenital sensorineural hearing loss. It has been estimated to account for 3-6%
      of the congenitally deaf population, upto 8-33% of individuals with RP and half
      of all cases with combined deafness and blindness (Vernon M,1969; Boughman JA et
      al,1983). The prevalence of Usher syndrome have been reported to range from 3.5
      to 6.2 per 100,000 in different populations (Vernon M,1969; Boughman JA et
      al,1983; Yan D et al, 2010). We report a case of Usher syndrome type I in an
      adult Nepalese male with typical congenital profound hearing loss, and night
      blindness secondary to retinitis pigmentosa.

PMID- 29634715
TI  - A typical manifestation of conjunctival epithelial inclusion cyst.
AB  - PURPOSE: To report a case of conjunctival epithelial inclusion cyst with atypical
      manifestation. METHODS: A 26-year-old male presented with a blackish-brown,
      subconjunctival mass located in palpebral conjunctiva of the upper eyelid. En
      bloc excision of the mass was performed and evaluated on histopathological
      examination. RESULTS: The excised mass was well defined, dark brown in colour and
      simulated a solid foreign body. On histopathological examination, the mass was
      lined by stratified squamous epithelium with florid hyperkeratosis and
      haemorrhage inside it, consistent with atypical conjunctival epithelial inclusion
      cyst. CONCLUSION: A careful clinical examination and histopathological study is
      essential for the differential diagnosis of subconjunctival mass as rarely they
      may present with atypical manifestations.

PMID- 29634716
TI  - Glaucoma in Asia- An epidemiological perspective.
AB  - Glaucoma is the third most common cause of global visual impairment. Bilateral
      blindness from glaucoma is projected to affect greater than 11 million
      individuals worldwide by the year 2020, with a disproportionately large number of
      the affected individuals being of Asian descent. The disease pattern, its
      response to treatment, and ground realities differ among various Asian countries.
      Over the past decade, there have been tremendous efforts for combating cataract
      blindness, but unfortunately few efforts in Asian countries have been made to
      establish comprehensive eye care programs in the community that include
      management of glaucoma. There is a need for education about the disease amongst
      the general public and continuing medical education and training of practicing
      ophthalmologists in addition to improvement of infrastructure to combat blindness
      due to glaucoma.

PMID- 29634717
TI  - Pharmacokinetics and interspecies scaling of a novel, orally-bioavailable anti
      cancer drug, SHetA2.
AB  - SHetA2 is a small molecule drug with promising cancer prevention and therapeutic
      activity and a high preclinical safety profile. The study objectives were to
      perform interspecies scaling and pharmacokinetic (PK) modeling of SHetA2 for
      human PK prediction. The PK data obtained from mice, rats, and dogs after
      intravenous and oral doses were used for simultaneous fitting to PK models. The
      disposition of SHetA2 was best described by a two-compartment model. The
      absorption kinetics was well characterized with a first-order absorption model
      for mice and rats, and a gastrointestinal transit model for dogs. Oral
      administration of SHetA2 showed a relatively fast absorption in mice, prolonged
      absorption (i.e., flip-flop kinetics) toward high doses in rats, and an early
      peak followed by a secondary peak at high doses in dogs. The oral bioavailability
      was 17.7-19.5% at 20-60 mg/kg doses in mice, <1.6% at 100-2000 mg/kg in rats, and
      11.2% at 100 mg/kg decreasing to 3.45% at 400 mg/kg and 1.11% at 1500 mg/kg in
      dogs. The disposition parameters were well correlated with the body weight for
      all species using the allometric equation, which predicted values of CL (17.3
      L/h), V1 (36.2 L), V2 (68.5 L) and CLD (15.2 L/h) for a 70-kg human. The oral
      absorption rate and bioavailability of SHetA2 was highly dependent on species,
      doses, formulations, and possibly other factors. The limited bioavailability at
      high doses was taken into consideration for the suggested first-in-human dose,
      which was much lower than the dose estimated based on toxicology studies. In
      summary, the present study provided the PK model for SHetA2 that depicted the
      disposition and absorption kinetics in preclinical species, and computational
      tools for human PK prediction.

PMID- 29634718
TI  - Acute glomerulonephritis with large confluent IgA-dominant deposits associated
      with liver cirrhosis.
AB  - BACKGROUND: Small glomerular IgA deposits have been reported in patients with
      liver cirrhosis, mainly as an incidental finding in autopsy studies. We recently
      encountered nine cirrhotic patients who presented with acute proliferative
      glomerulonephritis with unusually large, exuberant glomerular immune complex
      deposits, in the absence of systemic lupus erythematosus (SLE) or monoclonal
      gammopathy-related kidney disease. Deposits were typically IgA
      dominant/codominant. Our aim was to further elucidate the etiology, diagnostic
      pitfalls, and clinical outcomes. METHODS: We present clinical features and kidney
      biopsy findings of nine cirrhotic patients with an unusual acute immune complex
      glomerulonephritis. We also identified native kidney biopsies from all patients
      with liver cirrhosis at our institution over a 13-year period (January 2004 to
      December 2016) to evaluate presence of glomerular IgA deposits in them (n = 118).
      RESULTS: Six of nine cirrhotic patients with the large immune deposits had a
      recent/concurrent acute bacterial infection, prompting a diagnosis of infection
      associated glomerulonephritis and treatment with antibiotics. In the remaining
      three patients, no infection was identified and corticosteroids were initiated.
      Three of nine patients recovered kidney function (one recovered kidney function
      after liver transplant); three patients developed chronic kidney disease but
      remained off dialysis; two patients became dialysis-dependent and one patient
      developed sepsis and expired shortly after biopsy. Within the total cohort of 118
      patients with cirrhosis, 67 others also showed IgA deposits, albeit small; and 42
      patients had no IgA deposits. CONCLUSIONS: These cases provide support to the
      theory that liver dysfunction may compromise clearance of circulating immune
      complexes, enabling deposition in the kidney. At least in a subset of cirrhotic
      patients, a superimposed bacterial infection may serve as a "second-hit" and lead
      to acute glomerulonephritis with exuberant immune complex deposits. Therefore, a
      trial of antibiotics is recommended and caution is advised before
      immunosuppressive treatment is offered. Unfortunately, most of these patients
      have advanced liver failure; therefore both diagnosis and management remain a
      challenge.

PMID- 29634719
TI  - Cox-nnet: An artificial neural network method for prognosis prediction of high
      throughput omics data.
AB  - Artificial neural networks (ANN) are computing architectures with many
      interconnections of simple neural-inspired computing elements, and have been
      applied to biomedical fields such as imaging analysis and diagnosis. We have
      developed a new ANN framework called Cox-nnet to predict patient prognosis from
      high throughput transcriptomics data. In 10 TCGA RNA-Seq data sets, Cox-nnet
      achieves the same or better predictive accuracy compared to other methods,
      including Cox-proportional hazards regression (with LASSO, ridge, and mimimax
      concave penalty), Random Forests Survival and CoxBoost. Cox-nnet also reveals
      richer biological information, at both the pathway and gene levels. The outputs
      from the hidden layer node provide an alternative approach for survival-sensitive
      dimension reduction. In summary, we have developed a new method for accurate and
      efficient prognosis prediction on high throughput data, with functional
      biological insights. The source code is freely available at
      https://github.com/lanagarmire/cox-nnet.

PMID- 29634720
TI  - Segmentally homologous neurons acquire two different terminal neuropeptidergic
      fates in the Drosophila nervous system.
AB  - In this study, we identify the means by which segmentally homologous neurons
      acquire different neuropeptide fates in Drosophila. Ventral abdominal (Va)
      neurons in the A1 segment of the ventral nerve cord express DH31 and AstA
      neuropeptides (neuropeptidergic fate I) by virtue of Ubx activity, whereas the A2
      A4 Va-neurons express the Capa neuropeptide (neuropeptidergic fate II) under the
      influence of abdA. These different fates are attained through segment-specific
      programs of neural subtype specification undergone by segmentally homologous
      neurons. This is an attractive alternative by which Hox genes can shape
      Drosophila segmental neural architecture (more sophisticated than the previously
      identified binary "to live" or "not to live" mechanism). These data refine our
      knowledge of the mechanisms involved in diversifying neuronal identity within the
      central nervous system.

PMID- 29634722
TI  - A method for evaluating cognitively informed micro-targeted campaign strategies:
      An agent-based model proof of principle.
AB  - In political campaigns, perceived candidate credibility influences the
      persuasiveness of messages. In campaigns aiming to influence people's beliefs,
      micro-targeted campaigns (MTCs) that target specific voters using their
      psychological profile have become increasingly prevalent. It remains open how
      effective MTCs are, notably in comparison to population-targeted campaign
      strategies. Using an agent-based model, the paper applies recent insights from
      cognitive models of persuasion, extending them to the societal level in a novel
      framework for exploring political campaigning. The paper provides an initial
      treatment of the complex dynamics of population level political campaigning in a
      psychologically informed manner. Model simulations show that MTCs can take
      advantage of the psychology of the electorate by targeting voters favourable
      disposed towards the candidate. Relative to broad campaigning, MTCs allow for
      efficient and adaptive management of complex campaigns. Findings show that
      disliked MTC candidates can beat liked population-targeting candidates, pointing
      to societal questions concerning campaign regulations.

PMID- 29634721
TI  - Twelve-month clinical outcomes of 206 patients with chronic pulmonary
      aspergillosis.
AB  - There is a paucity of evidence surrounding the optimal antifungal therapy for use
      in chronic pulmonary aspergillosis (CPA) and the duration of therapy remains
      unclear. We retrospectively evaluated treatment outcomes, including change in
      quality of life scores (St George's Respiratory Questionnaire (QoL)), weight and
      Aspergillus IgG at 6 and 12 months following initiation of therapy in a cohort of
      206 CPA patients referred to the UK National Aspergillosis Centre (NAC),
      Manchester between April 2013 and March 2015. One hundred and forty-two patients
      (69%) were azole naive at presentation and 105 (74%) (Group A) were commenced on
      itraconazole, 27 (19%) on voriconazole, and 10 (7%) were not treated medically.
      The remainder (64 patients, 31%) had previously trialled, or remained on, azole
      therapy at inclusion (Group B) of whom 46 (72%) received itraconazole, 16 (25%)
      voriconazole, and 2 (3%) posaconazole. Initial therapy was continued for 12
      months in 78 patients (48%) of those treated; the azole was changed in 62 (32%)
      patients and discontinued in 56 (29%) patients for adverse reactions (32, 57%),
      azole resistance (11, 20%), clinical failure (8, 14%) or clinical stability (5,
      9%). Azole discontinuation rates were higher in Group B than in Group A (42% vs.
      22%, p = 0.003). For all patients who survived, weight increased (median of
      62.2Kg at baseline, to 64.8 at 12 months), mean Aspergillus IgG declined from 260
      (baseline) to 154 (12 months) and QoL improved from 62.2/100 (baseline) to
      57.2/100 (12 months). At 12 months, there was no difference in median survival
      between Groups A and B (95% vs. 91%, p = 0.173). The rate of emergence of
      resistance during therapy was 13% for itraconazole compared to 5% for
      voriconazole. Bronchial artery embolization was done in 9 (4.4%) patients and
      lobectomy in 7 (3.2%). The optimal duration of azole therapy in CPA is
      undetermined due to the absence of evidenced based endpoints allowing clinical
      trials to be undertaken. However we have demonstrated itraconazole and
      voriconazole are modestly effective for CPA, especially if given for 12 months,
      but fewer than 50% of patients manage this duration. This suggests extended
      therapy may be required for demonstrable clinical improvement.

PMID- 29634723
TI  - Elites are people, too: The effects of threat sensitivity on policymakers'
      spending priorities.
AB  - Recent research suggests that psychological needs can influence the political
      attitudes of ordinary citizens, often outside of their conscious awareness. In
      this paper, we investigate whether psychological needs also shape the spending
      priorities of political elites in the US. Most models of policymaking assume that
      political elites respond to information in relatively homogeneous ways. We
      suggest otherwise, and explore one source of difference in information
      processing, namely, threat sensitivity, which previous research links to
      increased support for conservative policy attitudes. Drawing on a sample of state
      level policymakers, we measure their spending priorities using a survey and their
      level of threat sensitivity using a standard psychophysiological measure (skin
      conductance). We find that, like ordinary citizens, threat sensitivity leads even
      state-level policymakers to prioritize spending on government polices that are
      designed to minimize threats.

PMID- 29634726
TI  - Correction: The Economics of Reproducibility in Preclinical Research.
AB  - [This corrects the article DOI: 10.1371/journal.pbio.1002165.].

PMID- 29634724
TI  - A Distalless-responsive enhancer of the Hox gene Sex combs reduced is required
      for segment- and sex-specific sensory organ development in Drosophila.
AB  - Hox genes are involved in the patterning of animal body parts at multiple levels
      of regulatory hierarchies. Early expression of Hox genes in different domains
      along the embryonic anterior-posterior (A/P) axis in insects, vertebrates, and
      other animals establishes segmental or regional identity. However, Hox gene
      function is also required later in development for the patterning and
      morphogenesis of limbs and other organs. In Drosophila, spatiotemporal modulation
      of Sex combs reduced (Scr) expression within the first thoracic (T1) leg
      underlies the generation of segment- and sex-specific sense organ patterns. High
      Scr expression in defined domains of the T1 leg is required for the development
      of T1-specific transverse bristle rows in both sexes and sex combs in males,
      implying that the patterning of segment-specific sense organs involves
      incorporation of Scr into the leg development and sex determination gene
      networks. We sought to gain insight into this process by identifying the cis-and
      trans-regulatory factors that direct Scr expression during leg development. We
      have identified two cis-regulatory elements that control spatially modulated Scr
      expression within T1 legs. One of these enhancers directs sexually dimorphic
      expression and is required for the formation of T1-specific bristle patterns. We
      show that the Distalless and Engrailed homeodomain transcription factors act
      through sequences in this enhancer to establish elevated Scr expression in
      spatially defined domains. This enhancer functions to integrate Scr into the
      intrasegmental gene regulatory network, such that Scr serves as a link between
      leg patterning, sex determination, and sensory organ development.

PMID- 29634725
TI  - Estimating the health and economic effects of the proposed US Food and Drug
      Administration voluntary sodium reformulation: Microsimulation cost-effectiveness
      analysis.
AB  - BACKGROUND: Sodium consumption is a modifiable risk factor for higher blood
      pressure (BP) and cardiovascular disease (CVD). The US Food and Drug
      Administration (FDA) has proposed voluntary sodium reduction goals targeting
      processed and commercially prepared foods. We aimed to quantify the potential
      health and economic impact of this policy. METHODS AND FINDINGS: We used a
      microsimulation approach of a close-to-reality synthetic population (US IMPACT
      Food Policy Model) to estimate CVD deaths and cases prevented or postponed,
      quality-adjusted life years (QALYs), and cost-effectiveness from 2017 to 2036 of
      3 scenarios: (1) optimal, 100% compliance with 10-year reformulation targets; (2)
      modest, 50% compliance with 10-year reformulation targets; and (3) pessimistic,
      100% compliance with 2-year reformulation targets, but with no further progress.
      We used the National Health and Nutrition Examination Survey and high-quality
      meta-analyses to inform model inputs. Costs included government costs to
      administer and monitor the policy, industry reformulation costs, and CVD-related
      healthcare, productivity, and informal care costs. Between 2017 and 2036, the
      optimal reformulation scenario achieving the FDA sodium reduction targets could
      prevent approximately 450,000 CVD cases (95% uncertainty interval: 240,000 to
      740,000), gain approximately 2.1 million discounted QALYs (1.7 million to 2.4
      million), and produce discounted cost savings (health savings minus policy costs)
      of approximately $41 billion ($14 billion to $81 billion). In the modest and
      pessimistic scenarios, health gains would be 1.1 million and 0.7 million QALYS,
      with savings of $19 billion and $12 billion, respectively. All the scenarios were
      estimated with more than 80% probability to be cost-effective (incremental
      cost/QALY < $100,000) by 2021 and to become cost-saving by 2031. Limitations
      include evaluating only diseases mediated through BP, while decreasing sodium
      consumption could have beneficial effects upon other health burdens such as
      gastric cancer. Further, the effect estimates in the model are based on
      interventional and prospective observational studies. They are therefore subject
      to biases and confounding that may have influenced also our model estimates.
      CONCLUSIONS: Implementing and achieving the FDA sodium reformulation targets
      could generate substantial health gains and net cost savings.

PMID- 29634727
TI  - Predicting essential proteins by integrating orthology, gene expressions, and PPI
      networks.
AB  - Identifying essential proteins is very important for understanding the minimal
      requirements of cellular life and finding human disease genes as well as
      potential drug targets. Experimental methods for identifying essential proteins
      are often costly, time-consuming, and laborious. Many computational methods for
      such task have been proposed based on the topological properties of protein
      protein interaction networks (PINs). However, most of these methods have limited
      prediction accuracy due to the noisy and incomplete natures of PINs and the fact
      that protein essentiality may relate to multiple biological factors. In this
      work, we proposed a new centrality measure, OGN, by integrating orthologous
      information, gene expressions, and PINs together. OGN determines a protein's
      essentiality by capturing its co-clustering and co-expression properties, as well
      as its conservation in the evolution process. The performance of OGN was tested
      on the species of Saccharomyces cerevisiae. Compared with several published
      centrality measures, OGN achieves higher prediction accuracy in both working
      alone and ensemble.

PMID- 29634728
TI  - Forest management strategy affects saproxylic beetle assemblages: A comparison of
      even and uneven-aged silviculture using direct and indirect sampling.
AB  - Management of forest for wood production has altered ecosystem structures and
      processes and led to habitat loss and species extinctions, worldwide. Deadwood is
      a key resource supporting forest biodiversity, and commonly declines following
      forest management. However, different forest management methods affect dead wood
      differently. For example, uneven-aged silviculture maintains an age-stratified
      forest with ongoing dead wood production, while even-aged silviculture breaks
      forest continuity, leading to long periods without large trees. We asked how
      deadwood-dependent beetles respond to different silvicultural practices and if
      their responses depend on deadwood volume, and beetles preference for decay
      stages of deadwood. We compared beetle assemblages in five boreal forest types
      with different management strategies: clearcutting and thinning (both
      representing even-aged silviculture), selective felling (representing uneven-aged
      silviculture), reference and old growth forest (both uneven-aged controls without
      a recent history [~50 years] of management, but the latter with high conservation
      values). We collected beetles using window traps and by sieving the bark from
      experimental logs (bolts). Beetle assemblages on clear-cuts differed from all
      other stand types, regardless of trapping method or decay stage preference.
      Thinning differed from reference stands, indicating incomplete recovery after
      clear-cutting, while selective felling differed only from clear-cuts. In contrast
      to our predictions, early and late successional species responded similarly to
      different silvicultural practices. However, there were indications of marginal
      assemblage differences both between thinned stands and selective felling and
      between thinned and old growth stands (p = 0.10). The stand volume of early decay
      stage wood influenced assemblage composition of early, but not late successional
      species. Uneven-aged silviculture maintained species assemblages similar to those
      of the reference and old growth stands and might therefore be a better management
      option when considering biodiversity conservation.

PMID- 29634729
TI  - Automated calibration and control for polarization-resolved second harmonic
      generation on commercial microscopes.
AB  - Polarization-resolved second harmonic generation (P-SHG) microscopy has evolved
      as a promising technique to reveal subresolution information about the structure
      and orientation of ordered biological macromolecules. To extend the adoption of
      the technique, it should be easily integrated onto commercial laser scanning
      microscopes. Furthermore, procedures for easy calibration and assessment of
      measurement accuracy are essential, and measurements should be fully automated to
      allow for analysis of large quantities of samples. In this paper we present a
      setup for P-SHG which is readily incorporated on commercial multiphoton
      microscopes. The entire system is completely automated which allows for rapid
      calibration through the freely available software and for automated imaging for
      different polarization measurements, including linear and circular polarization
      of the excitation beam. The results show that calibration settings are highly
      system dependent. We also show that the accuracy of the polarization control is
      easily quantified and that it varies between systems. The accuracy can be tuned
      by iterative alignment of optics or a more fine-grained calibration procedure.
      Images of real samples show that the red accuracy of the results is easily
      visualized with the automated setup. Through this system we believe that P-SHG
      could develop a wider adoption in biomedical applications.

PMID- 29634730
TI  - Effect of ENSO events on larval and juvenile duration and transport of Japanese
      eel (Anguilla japonica).
AB  - Spawning ground of Japanese eel (Anguilla japonica) is located near the West
      Mariana Ridge seamount. The species travels through the North Equatorial Current
      (NEC) and then enters the Kuroshio Current (KC) on the migration toward East
      Asian growth habitats. Therefore, El Nino-Southern Oscillation (ENSO) events
      serve as the potentially important drivers of interannual variability across the
      equatorial Pacific. Because the NEC bifurcation and salinity profiles are related
      to ENSO events, we investigated the influence of locations of the NEC bifurcation
      and salinity front on the success of larval entry to the KC by numerically
      modeling particle transport in ocean currents from 1972 to 2013 and possible
      effects on the size of glass eels at continental recruitment and, via
      otolithometry on the duration of larval migration. Circulation and hydrography
      used for particle tracking were obtained from the results of the Model for
      Interdisciplinary Research on Climate (MIROC) high-resolution forecasting
      experiment. Our results demonstrated that during El Nino years, (1) the southward
      movement of the salinity front might cause the larvae to experience slower
      currents and (2) the northward movement of the NEC bifurcation might broaden the
      separation between their spawning ground and NEC bifurcation, thus prolonging the
      time needed for the larvae to enter the KC from their spawning ground, because of
      which the duration of entrainment in the water column and body size increase when
      eels reach estuarine waters. In addition, this might cause more water to flow
      into the Mindanao Current (MC), leading to a decline in the rate at which larvae
      get entrained into the KC.

PMID- 29634731
TI  - The development of the own-race advantage in school-age children: A morphing face
      paradigm.
AB  - Previous studies examining the other-race effect in school-age children mostly
      focused on recognition memory performance. Here we investigated perceptual
      discriminability for Asian-like versus Caucasian-like morph faces in school-age
      Taiwanese children and adults. One-hundred-and-two 5- to 12-year-old children and
      twenty-three adults performed a sequential same/different face matching task,
      where they viewed an Asian- or a Caucasian-parent face followed by either the
      same parent face or a different morphed face (containing 15%, 30%, 45%, or 60%
      contribution from the other parent face) and judged if the two faces looked the
      same. We computed the d' as the sensitivity index for each age groups. We also
      analyzed the group mean rejection rates as a function of the morph level and
      fitted with a cumulative normal distribution function. Results showed that the
      adults and the oldest 11-12-year-old children exhibited a greater sensitivity
      (d') and a smaller discrimination threshold (MU) in the Asian-parent condition
      than those in the Caucasian-parent condition, indicating the presence of an own
      race advantage. On the contrary, 5- to 10-year-old children showed an equal
      sensitivity and similar discrimination thresholds for both conditions, indicating
      an absence of the own-race advantage. Moreover, a gradual development in
      enhancing the discriminability for the Asian-parent condition was observed from
      age 5 to 12; however, the progression in the Caucasian-parent condition was less
      apparent. In sum, our findings suggest that expertise in face processing may take
      the entire childhood to develop, and supports the perceptual learning view of the
      other-race effect-the own-race advantage seen in adulthood likely reflects a
      result of prolonged learning specific to faces most commonly seen in one's visual
      environment such as own-race faces.

PMID- 29634732
TI  - Experimental study on the relationship between the mineral production capability
      and the physiochemical properties in the coproduction of Q phase
      3CaO.3Al2O3.CaSO4 cement clinker.
AB  - A coproduction tests of quaternary (Q) phase(6CaO.4Al2O3.MgO.SiO2) 
      3CaO.3Al2O3.CaSO4 cement clinker and an experimental study on the relationship
      between the mineral production capability and the physiochemical properties are
      conducted in a two-stage multiphase reaction test bed with Changguang coal. X-ray
      diffractometer (XRD) analyses are performed on the coproduction clinker samples.
      The results demonstrate that, with the reduction in particle sizes of the coal
      powder and the additives and expanded screening level differences between them,
      both the proportion of Q phase and the mass of 3CaO.3Al2O3.CaSO4 in the clinker
      increase accordingly. When mixed coal powder particles are prepared through
      reducing particle sizes and expanding screening level differences between coal
      powder and additives, the additives CaO and MgO are more likely to be enclosed by
      coal powder to form globular polymerized particles. In addition, this preparation
      aids in polymerization and promotes even distribution of CaO, MgO and coal
      minerals, thus facilitating clinker mineral formation reactions of inorganic
      substances in the mixed coal powder. Target minerals, such as 2CaO.SiO2 and Q
      phase, are found in both industrial high-calcium limestone and low-calcium
      limestone coproduction clinker samples. A diffraction peak of free CaO is also
      evident in both samples. Compared with a coproduction clinker sample of high
      calcium limestone, that of low-calcium limestone exhibits higher diffraction
      peaks for 2CaO.SiO2 and Q phase. With the current state of the art, it is not yet
      the optimum choice to substitute CaCO3 for CaO in Q-phase cement clinker
      coproduction. Before the technology matures and gains practical application,
      further study on the form and the mixing process of calcium-based additives for
      cement clinker coproduction will be required.

PMID- 29634733
TI  - Increased male bias in eider ducks can be explained by sex-specific survival of
      prime-age breeders.
AB  - In contrast to theoretical predictions of even adult sex ratios, males are
      dominating in many bird populations. Such bias among adults may be critical to
      population growth and viability. Nevertheless, demographic mechanisms for biased
      adult sex ratios are still poorly understood. Here, we examined potential
      demographic mechanisms for the recent dramatic shift from a slight female bias
      among adult eider ducks (Somateria mollissima) to a male bias (about 65% males)
      in the Baltic Sea, where the species is currently declining. We analysed a nine
      year dataset on offspring sex ratio at hatching based on molecularly sexed
      ducklings of individually known mothers. Moreover, using demographic data from
      long-term individual-based capture-recapture records, we investigated how sex
      specific survival at different ages after fledgling can modify the adult sex
      ratio. More specifically, we constructed a stochastic two-sex matrix population
      model and simulated scenarios of different survival probabilities for males and
      females. We found that sex ratio at hatching was slightly female-biased (52.8%)
      and therefore unlikely to explain the observed male bias among adult birds. Our
      stochastic simulations with higher survival for males than for females revealed
      that despite a slight female bias at hatching, study populations shifted to a
      male-biased adult sex ratio (> 60% males) in a few decades. This shift was driven
      by prime reproductive-age individuals (>=5-year-old), with sex-specific survival
      of younger age classes playing a minor role. Hence, different age classes
      contributed disproportionally to population dynamics. We argue that an
      alternative explanation for the observed male dominance among adults-sex-biased
      dispersal-can be considered redundant and is unlikely, given the ecology of the
      species. The present study highlights the importance of considering population
      structure and age-specific vital rates when assessing population dynamics and
      management targets.

PMID- 29634734
TI  - Characterization of lncRNAs involved in cold acclimation of zebrafish ZF4 cells.
AB  - Long non-coding RNAs (lncRNAs) are increasingly regarded as a key role in
      regulating diverse biological processes in various tissues and species. Although
      the cold responsive lncRNAs have been reported in plants, no data is available on
      screening and functional prediction of lncRNAs in cold acclimation in fish so
      far. Here we compared the expression profile of lncRNAs in cold acclimated
      zebrafish embryonic fibroblast cells (ZF4) cultured at 18 degrees C for 30 days
      with that of cells cultured at 28 degrees C as control by high-throughput
      sequencing. Totally 8,363 novel lncRNAs were identified. Including known and
      novel lncRNAs, there are 347 lncRNAs up-regulated and 342 lncRNAs down-regulated
      in cold acclimated cells. Among the differentially expressed lncRNAs, 74 and 61
      were detected only in control cells or cold-acclimated cells, respectively. The
      Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment
      analyses of adjacent genes to the differentially expressed lncRNAs showed that
      the enriched genes are involved in electron transport, cell adhesion, oxidation
      reduction process, and so on. We also predicted the target genes of the
      differentially expressed lncRNAs by looking for interactions between lncRNAs and
      mRNAs, and constructed an interaction network. In summary, our genome-wide
      systematic identification and functional prediction of cold responsive lncRNAs in
      zebrafish cells suggests a crucial role of lincRNAs in cold acclimation in fish.

PMID- 29634735
TI  - Placental pathology predicts infantile physical development during first 18
      months in Japanese population: Hamamatsu birth cohort for mothers and children
      (HBC Study).
AB  - The present study aimed to investigate the relationship between placental
      pathological findings and physiological development during the neonate and
      infantile periods. Study participants were 258 infants from singleton pregnancies
      enrolled in the Hamamatsu Birth Cohort for Mothers and Children (HBC Study) whose
      placentas were stored in our pathological division. They were followed up from
      birth to 18 months of age. Physiological development (body weight and the
      ponderal index [PI]) was assessed at 0, 1, 4, 6, 10, 14, and 18 months. Placental
      blocks were prepared by random sampling and eleven pathological findings were
      assessed, as follows: 'Accelerated villous maturation', 'Decidual vasculopathy',
      'Thrombosis or Intramural fibrin deposition', 'Avascular villi', 'Delayed villous
      maturation', 'Maternal inflammatory response', 'Fetal inflammatory response',
      'Villitis of unknown etiology (VUE)', 'Deciduitis', 'Maternal vascular
      malperfusion', and 'Fetal vascular malperfusion'. Mixed model analysis with the
      use of the xtmixed command by the generic statistical software, Stata version
      13.1., identified 'Accelerated villous maturation' and 'Maternal vascular
      malperfusion' as significant predictors of a lower body weight and 'Deciduitis'
      as a significant predictor of a small PI, throughout the first 18 months of life.
      In conclusion, the present study is the first to demonstrate that some
      pathological findings of the placenta are associated with changes in infantile
      physical development during the initial 18 months of life in the Japanese
      population.

PMID- 29634736
TI  - Cost-effectiveness of daclatasvir plus asunaprevir for chronic hepatitis C
      genotype 1b treatment-naive patients in China.
AB  - BACKGROUND: Hepatitis C is the second fastest growing infectious disease in
      China. The standard-of-care for chronic hepatitis C in China is Pegylated
      interferon plus ribavirin (PR), which is associated with tolerability and
      efficacy issues. An interferon- and ribavirin-free, all-oral regimen comprising
      daclatasvir (DCV) and asunaprevir (ASV), which displays higher efficacy and
      tolerability, has recently been approved in China. OBJECTIVES: This study is to
      estimate the cost-effectiveness of DCV+ASV (24 weeks) for chronic hepatitis C
      genotype 1b treatment-naive patients compared with PR regimen (48 weeks) in
      China. METHODS: A cohort-based Markov model was developed from Chinese payer
      perspective to project the lifetime outcomes of treating 10,000 patients with an
      average age of 44.5 with two hypothetical regimens, DCV+ASV and PR. Chinese
      specific health state costs and efficacy data were used. The annual discount rate
      was 5%. Base-case analysis and sensitivity analysis were conducted. RESULTS: For
      HCV Genotype 1b treatment-naive patients, DCV+ASV proved to be dominant over PR,
      with a cost saving of Y33,480(5,096 USD) and gains in QALYs and life years of
      1.29 and 0.85, respectively. The lifetime risk of compensated cirrhosis,
      decompensated cirrhosis, hepatocellular carcinoma and liver-related death was
      greatly reduced with DCV+ASV. Univariate sensitivity analysis demonstrated that
      key influencers were the discount rate, time horizon, initial disease severity
      and sustained virological response rate of DCV+ASV, with all scenarios resulting
      in additional benefit. Probabilistic sensitivity analysis demonstrated that
      DCV+ASV has a high likelihood (100%) of being cost-effective. CONCLUSION: DCV+ASV
      is not only an effective and well-tolerated regimen to treat chronic HCV genotype
      1b infection treatment-naive patients, but also is more cost-effective than PR
      regimen. DCV+ASV can benefit both the public health and reimbursement system in
      China.

PMID- 29634737
TI  - Prevalence and factors leading to unemployment in MS (multiple sclerosis)
      patients undergoing immunomodulatory treatment in Poland.
AB  - Multiple Sclerosis (MS) is the most common, primary neurogenic cause of
      disability among young adults. We investigated demographic and clinical factors
      associated with unemployment on the example of 150 MS patients receiving
      immunomodulatory treatment in Poland. This study was based on clinical evaluation
      and collection of self-reported questionnaires, with an attention to self
      motivation, severe fatigue and moderate disability. Patients who were unemployed
      (40% of all patients) had a mean disease duration of almost 5 years. Older
      (p<0.001), less educated (p = 0.007) and more severely disabled patients
      (p<0,001) were most likely to be unemployed. Moderate disability (OR = 11.089 95%
      CI: 4.11-34.201, p<0,001), severe fatigue (OR = 2.625 95% CI: 1.02-6.901, p =
      0,046) and lower level of self-motivation (KNS) (OR = 0.947, 95% CI: 0.896-0.006,
      p = 0.042) were independently associated with unemployment.

PMID- 29634738
TI  - Interaction of childhood urbanicity and variation in dopamine genes alters adult
      prefrontal function as measured by functional magnetic resonance imaging (fMRI).
AB  - Brain phenotypes showing environmental influence may help clarify unexplained
      associations between urban exposure and psychiatric risk. Heritable prefrontal
      fMRI activation during working memory (WM) is such a phenotype. We hypothesized
      that urban upbringing (childhood urbanicity) would alter this phenotype and
      interact with dopamine genes that regulate prefrontal function during WM.
      Further, dopamine has been hypothesized to mediate urban-associated factors like
      social stress. WM-related prefrontal function was tested for main effects of
      urbanicity, main effects of three dopamine genes-catechol-O-methyltransferase
      (COMT), dopamine receptor D1 (DRD1), and dopamine receptor D2 (DRD2)-and,
      importantly, dopamine gene-by-urbanicity interactions. For COMT, three
      independent human samples were recruited (total n = 487). We also studied 253
      subjects genotyped for DRD1 and DRD2. 3T fMRI activation during the N-back WM
      task was the dependent variable, while childhood urbanicity, dopamine genotype,
      and urbanicity-dopamine interactions were independent variables. Main effects of
      dopamine genes and of urbanicity were found. Individuals raised in an urban
      environment showed altered prefrontal activation relative to those raised in
      rural or town settings. For each gene, dopamine genotype-by-urbanicity
      interactions were shown in prefrontal cortex-COMT replicated twice in two
      independent samples. An urban childhood upbringing altered prefrontal function
      and interacted with each gene to alter genotype-phenotype relationships. Gene
      environment interactions between multiple dopamine genes and urban upbringing
      suggest that neural effects of developmental environmental exposure could
      mediate, at least partially, increased risk for psychiatric illness in urban
      environments via dopamine genes expressed into adulthood.

PMID- 29634739
TI  - Metabolomic markers of fertility in bull seminal plasma.
AB  - Metabolites play essential roles in biological systems, but detailed identities
      and significance of the seminal plasma metabolome related to bull fertility are
      still unknown. The objectives of this study were to determine the comprehensive
      metabolome of seminal plasma from Holstein bulls and to ascertain the potential
      of metabolites as biomarkers of bull fertility. The seminal plasma metabolome
      from 16 Holstein bulls with two fertility rates were determined by gas
      chromatography-mass spectrometry (GC-MS). Multivariate and univariate analyses of
      the data were performed, and the pathways associated with the seminal plasma
      metabolome were identified using bioinformatics approaches. Sixty-three
      metabolites were identified in the seminal plasma of all bulls. Fructose was the
      most abundant metabolite in the seminal fluid, followed for citric acid, lactic
      acid, urea and phosphoric acid. Androstenedione, 4-ketoglucose, D-xylofuranose, 2
      oxoglutaric acid and erythronic acid represented the least predominant
      metabolites. Partial-Least Squares Discriminant Analysis (PLSDA) revealed a
      distinct separation between high and low fertility bulls. The metabolites with
      the greatest Variable Importance in Projection score (VIP > 2) were 2-oxoglutaric
      acid and fructose. Heat-map analysis, based on VIP score, and univariate analysis
      indicated that 2-oxoglutaric acid was less (P = 0.02); whereas fructose was
      greater (P = 0.02) in high fertility than in low fertility bulls. The current
      study is the first to describe the metabolome of bull seminal plasma using GC-MS
      and presented metabolites such as 2-oxoglutaric acid and fructose as potential
      biomarkers of bull fertility.

PMID- 29634740
TI  - Functional self-assembled neocartilage as part of a biphasic osteochondral
      construct.
AB  - Bone-to-bone integration can be obtained by osteoconductive ceramics such as
      hydroxyapatite (HAp) and beta-tricalcium phosphate (beta-TCP), but cartilage-to
      cartilage integration is notoriously difficult. Many cartilage repair therapies,
      including microfracture and mosaicplasty, capitalize on the reparative aspects of
      subchondral bone due to its resident population of stem cells and vascularity. A
      strategy of incorporating tissue engineered neocartilage into a ceramic to form
      an osteochondral construct may serve as a suitable alternative to achieve
      cartilage graft fixation. The use of a tissue engineered osteochondral construct
      to repair cartilage defects may also benefit from the ceramic's proximity to
      underlying bone and abundant supply of progenitor cells and nutrients. The
      objective of the first study was to compare HAp and beta-TCP ceramics, two widely
      used ceramics in bone regeneration, in terms of their ability to influence
      neocartilage interdigitation at an engineered osteochondral interface. Additional
      assays quantified ceramic pore size, porosity, and compressive strength. The
      compressive strength of HAp was six times higher than that of beta-TCP due to
      differences in porosity and pore size, and HAp was thus carried forward in the
      second study as the composition with which to engineer an osteochondral
      construct. Importantly, it was shown that incorporation of the HAp ceramic in
      conjunction with the self-assembling process resulted in functionally viable
      neocartilage. For example, only collagen/dry weight and ultimate tensile strength
      of the chondral control constructs remained significantly greater than the
      neocartilage cut off the osteochondral constructs. By demonstrating that the
      functional properties of engineered neocartilage are not negatively affected by
      the inclusion of an HAp ceramic in culture, neocartilage engineering strategies
      may be directly applied to the formation of an osteochondral construct.

PMID- 29634742
TI  - Analysis of exergy efficiency of a super-critical compressed carbon dioxide
      energy-storage system based on the orthogonal method.
AB  - Super-critical carbon dioxide energy-storage (SC-CCES) technology is a new type
      of gas energy-storage technology. This paper used orthogonal method and variance
      analysis to make significant analysis on the factors which would affect the
      thermodynamics characteristics of the SC-CCES system and obtained the significant
      factors and interactions in the energy-storage process, the energy-release
      process and the whole energy-storage system. Results have shown that the
      interactions in the components have little influence on the energy-storage
      process, the energy-release process and the whole energy-storage process of the
      SC-CCES system, the significant factors are mainly on the characteristics of the
      system component itself, which will provide reference for the optimization of the
      thermal properties of the energy-storage system.

PMID- 29634741
TI  - Trends in use of acupuncture among adults in Taiwan from 2002 to 2011: A
      nationwide population-based study.
AB  - In recent years, acupuncture has gained in popularity worldwide. However, recent
      epidemiological studies are lacking. We conducted this study to investigate the
      trends in acupuncture utilization among adults in Taiwan from 2002 to 2011. We
      analyzed data from the Longitudinal Health Insurance Database 2000 (LHID 2000),
      which contains all original claims data for 1 million beneficiaries randomly
      sampled from the registry of all beneficiaries enrolled in the National Health
      Insurance (NHI) program in 2000. The one-year prevalence of acupuncture use among
      adults increased from 7.98% in 2002 to 10.9% in 2011. Acupuncture use
      significantly increased yearly (incidence rate ratio = 1.04, 95% CI = 1.03-1.05,
      p<0.001). Patients who were female, were middle-aged, resided in highly urbanized
      areas and suffered from injury or disorders of the musculoskeletal system were
      prone to more frequent acupuncture use. Our study revealed that the utilization
      of acupuncture became increasingly popular in Taiwan from 2002 to 2011. Our
      findings may provide useful information for clinical practice and research as
      well as for health policy decision making.

PMID- 29634743
TI  - High susceptibility of magpie (Pica pica) to experimental infection with lineage
      1 and 2 West Nile virus.
AB  - West Nile virus (WNV), a zoonotic pathogen naturally transmitted by mosquitoes
      whose natural hosts are birds, has spread worldwide during the last few decades.
      Resident birds play an important role in flavivirus epidemiology, since they can
      serve as reservoirs and facilitate overwintering of the virus. Herein, we report
      the first experimental infection of magpie (Pica pica) with two strains of West
      Nile virus, lineages 1 (NY-99) and 2 (SRB Novi-Sad/12), which are currently
      circulating in Europe. Magpies were highly susceptible to WNV infection, with
      similar low survival rates (30% and 42.8%) for both lineages. All infected
      magpies developed viremia detectable at 3 days post-infection with titers above
      those necessary for successful transmission of WNV to a mosquito. Neutralizing
      antibodies were detected at all time points analyzed (from 7 to 17 days post
      infection). WNV genome was detected in the brains and hearts of all magpies that
      succumbed to the infection, and, in some of the surviving birds. WNV-RNA was
      amplified from swabs (oral and cloacal) at 3, 6 and 7 days post-infection and
      feather pulps, from 3 to 17 days post-infection, of infected animals. Even more,
      infectious virus was recovered from swabs up to 7 days post-infection and from
      feather pulps up to 10 days post infection. Sham-infected control animals were
      negative for viremia, viral RNA, and antibodies. These results suggest that the
      magpie, which is one of the most abundant corvid species in Europe, could
      represent a source of WNV transmission for birds and humans. Our observations
      shed light on the pathogenesis, transmission, and ecology of WNV and can benefit
      the implementation of surveillance and control programs.

PMID- 29634744
TI  - Elucidation and functional characterization of CsPSY and CsUGT promoters in
      Crocus sativus L.
AB  - The dried stigmas of Crocus sativus constitute the saffron, which is considered
      to be the costliest spice of the world. Saffron is valuable for its constituents,
      which are mainly apocarotenoids. In order to enhance the production of
      apocarotenoids, it is imperative to understand the regulation of apocarotenoid
      biosynthetic pathway. In C. sativus, although the pathway has been elucidated,
      the information regarding the regulation of the pathwaygenes is scanty. During
      the present investigation, the characterization of promoters regulating the
      expression of two important genes i.e. CsPSY and CsUGT was performed. We
      successfully cloned the promoters of both the genes, which were functionally
      characterized in Crocus sativus and Nicotiana tabaccum. In silico analysis of the
      promoters demonstrated the presence of several important cis regulatory elements
      responding tolight, hormonesand interaction with transcription factors (TFs).
      Further analysis suggested the regulation of CsPSY promoter by Abscisic acid
      (ABA) and that of CsUGT by Gibberellic acid (GA). In addition, we also observed
      ABA and GA mediated modulation in the expression of significant TFs and CsPSY and
      CsUGT transcripts. Overall, the study addresses issues related to regulation of
      key genes of apocarotenoid pathway in C.sativus.

PMID- 29634745
TI  - Spatial clustering of Borrelia burgdorferi sensu lato within populations of
      Allen's chipmunks and dusky-footed woodrats in northwestern California.
AB  - The ecology of Lyme borreliosis is complex in northwestern California, with
      several potential reservoir hosts, tick vectors, and genospecies of Borrelia
      burgdorferi sensu lato. The primary objective of this study was to determine the
      fine-scale spatial distribution of different genospecies in four rodent species,
      the California ground squirrel (Otospermophilus beecheyi), northern flying
      squirrel (Glaucomys sabrinus), dusky-footed woodrat (Neotoma fuscipes), and
      Allen's chipmunk (Neotamias senex). Rodents were live-trapped between June 2004
      and May 2005 at the Hoopa Valley Tribal Reservation (HVTR) in Humboldt County,
      California. Ear-punch biopsies obtained from each rodent were tested by
      polymerase chain reaction (PCR) and sequencing analysis. The programs ArcGIS and
      SaTScan were used to examine the spatial distribution of genospecies. Multinomial
      log-linear models were used to model habitat and host-specific characteristics
      and their effect on the presence of each borrelial genospecies. The Akaike
      information criterion (AICc) was used to compare models and determine model fit.
      Borrelia burgdorferi sensu stricto was primarily associated with chipmunks and B.
      bissettiae largely with woodrats. The top model included the variables "host
      species", "month", and "elevation" (weight = 0.84). Spatial clustering of B.
      bissettiae was detected in the northwestern section of the HVTR, whereas B.
      burgdorferi sensu stricto was clustered in the southeastern section. We conclude
      that the spatial distribution of these borreliae are driven at least in part by
      host species, time-of-year, and elevation.

PMID- 29634746
TI  - Geographical and temporal patterns of rabies post exposure prophylaxis (PEP)
      incidence in humans in the Mekong River Delta and Southeast Central Coast regions
      in Vietnam from 2005 to 2015.
AB  - BACKGROUND: In Vietnam, rabies has been a notifiable disease for more than 40
      years. Over the last five years, on average, more than 350,000 people per year
      have been bitten by dogs and cats while more than 80 human deaths have been
      reported yearly. No studies have been conducted to evaluate the geographical and
      temporal patterns of rabies in humans in Vietnam. Therefore, the main objective
      of this study was to assess the geographical and temporal distributions of rabies
      post exposure prophylaxis (PEP) incidence in humans in Vietnam from 2005 to 2015.
      METHODS: Average incidence rabies (AIR) PEP rates for every 3 or 4 years (2005
      2008, 2009-2012 and 2013-2015) were calculated to describe the spatial
      distribution of rabies PEP. Hotspot analysis was implemented to identify patterns
      of spatial significance using the Getis-Ord Gi statistic. For temporal pattern
      analysis, two regions [Mekong River Delta (MRD) and Southeast Central Coast
      (SCC)], with the highest incidence rates, and the seasonal-decomposition
      procedure based on loess (STL), were compared to assess their temporal patterns
      of rabies PEP. FINDINGS: We found hotspots in southern Vietnam and coldspots in
      northern Vietnam during the study period. Rabies cases were limited to specific
      areas. In addition, the hotspot analysis showed that new risk areas were
      identified in each period which were not observed in incidence rate maps. The
      seasonal plots showed seasonal patterns with a strong peak in February/July and a
      minor peak in October/December in the MRD region. However, in the SCC, a small
      peak was detected at the early part of each year and a strong peak in the middle
      of each year. CONCLUSION: Our findings provide insight into understanding the
      geographical and seasonal patterns of rabies PEP in Vietnam. This study provides
      evidence to aid policy makers when making decisions and investing resources. Such
      information may also be utilized to raise public awareness to prevent rabies
      exposures and reduce unnecessary PEP.

PMID- 29634747
TI  - Personality traits in companion dogs-Results from the VIDOPET.
AB  - Individual behavioural differences in pet dogs are of great interest from a basic
      and applied research perspective. Most existing dog personality tests have
      specific (practical) goals in mind and so focused only on a limited aspect of
      dogs' personality, such as identifying problematic (aggressive or fearful)
      behaviours, assessing suitability as working dogs, or improving the results of
      adoption. Here we aimed to create a comprehensive test of personality in pet dogs
      that goes beyond traditional practical evaluations by exposing pet dogs to a
      range of situations they might encounter in everyday life. The Vienna Dog
      Personality Test (VIDOPET) consists of 15 subtests and was performed on 217 pet
      dogs. A two-step data reduction procedure (principal component analysis on each
      subtest followed by an exploratory factor analysis on the subtest components)
      yielded five factors: Sociability-obedience, Activity-independence, Novelty
      seeking, Problem orientation, and Frustration tolerance. A comprehensive
      evaluation of reliability and validity measures demonstrated excellent inter- and
      intra-observer reliability and adequate internal consistency of all factors.
      Moreover the test showed good temporal consistency when re-testing a subsample of
      dogs after an average of 3.8 years-a considerably longer test-retest interval
      than assessed for any other dog personality test, to our knowledge. The construct
      validity of the test was investigated by analysing the correlations between the
      results of video coding and video rating methods and the owners' assessment via a
      dog personality questionnaire. The results demonstrated good convergent as well
      as discriminant validity. To conclude, the VIDOPET is not only a highly reliable
      and valid tool for measuring dog personality, but also the first test to show
      consistent behavioural traits related to problem solving ability and frustration
      tolerance in pet dogs.

PMID- 29634748
TI  - Unmasking the complexity of species identification in Australasian flying-foxes.
AB  - Pteropus (flying-foxes) are a speciose group of non-echolocating large bats, with
      five extant Australian species and 24 additional species distributed amongst the
      Pacific Islands. In 2015, an injured flying-fox with unusual facial markings was
      found in Sydney, Australia, following severe and widespread storms. Based on an
      initial assessment, the individual belonged to Pteropus but could not be readily
      identified to species. As a consequence, four hypotheses for its
      identification/origin were posited: the specimen represented (1) an undescribed
      Australian species; or (2) a morphological variant of a recognised Australian
      species; or (3) a hybrid individual; or (4) a vagrant from the nearby Southwest
      Pacific Islands. We used a combination of morphological and both mitochondrial-
      and nuclear DNA-based identification methods to assess these hypotheses. Based on
      the results, we propose that this morphologically unique Pteropus most likely
      represents an unusual P. alecto (black flying-fox) potentially resulting from
      introgression from another Pteropus species. Unexpectedly, this individual, and
      the addition of reference sequence data from newly vouchered specimens, revealed
      a previously unreported P. alecto mitochondrial DNA lineage. This lineage was
      distinct from currently available haplotypes. It also suggests long-term
      hybridisation commonly occurs between P. alecto and P. conspicillatus (spectacled
      flying-fox). This highlights the importance of extensive reference data, and the
      inclusion of multiple vouchered specimens for each species to encompass both
      intraspecific and interspecific variation to provide accurate and robust species
      identification. Moreover, our additional reference data further demonstrates the
      complexity of Pteropus species relationships, including hybridisation, and
      potential intraspecific biogeographical structure that may impact on their
      management and conservation.

PMID- 29634749
TI  - Dynamic multi-segmental postural control in patients with chronic non-specific
      low back pain compared to pain-free controls: A cross-sectional study.
AB  - Reduced postural control is thought to contribute to the development and
      persistence of chronic non-specific low back pain (CNLBP). It is therefore
      frequently assessed in affected patients and commonly reported as the average
      amount of postural sway while standing upright under a variety of sensory
      conditions. These averaged linear outcomes, such as mean centre of pressure (CP)
      displacement or mean CP surface areas, may not reflect the true postural status.
      Adding nonlinear outcomes and multi-segmental kinematic analysis has been
      reported to better reflect the complexity of postural control and may detect
      subtler postural differences. In this cross-sectional study, a combination of
      linear and nonlinear postural parameters were assessed in patients with CNLBP (n
      = 24, 24-75 years, 9 females) and compared to symptom-free controls (CG, n = 34,
      22-67 years, 11 females). Primary outcome was postural control measured by
      variance of joint configurations (uncontrolled manifold index, UI), confidence
      ellipse surface areas (CEA) and approximate entropy (ApEn) of CP dispersion
      during the response phase of a perturbed postural control task on a swaying
      platform. Secondary outcomes were segment excursions and clinical outcome
      correlates for pain and function. Non-parametric tests for group comparison with
      P-adjustment for multiple comparisons were conducted. Principal component
      analysis was applied to identify patterns of segmental contribution in both
      groups. CNLBP and CG performed similarly with respect to the primary outcomes.
      Comparison of joint kinematics revealed significant differences of hip (P < .001)
      and neck (P < .025) angular excursion, representing medium to large group effects
      (r's = .36 - .51). Significant (P's < .05), but moderate correlations of ApEn (r
      = -.42) and UI (r = -.46) with the health-related outcomes were observed. These
      findings lend further support to the notion that averaged linear outcomes do not
      suffice to describe subtle postural differences in CNLBP patients with low to
      moderate pain status.

PMID- 29634750
TI  - A fluidics-based impact sensor.
AB  - Microelectromechanical systems (MEMS)-based high-performance accelerometers are
      ubiquitously used in various electronic devices. However, there is an existing
      need to detect physical impacts using low-cost devices with no electronic
      circuits or a battery. We designed and fabricated an impact sensor prototype
      using a commercial stereolithography apparatus that only consists of a plastic
      housing and working fluids. The sensor device responds to the instantaneous
      acceleration (impact) by deformation and pinch off of a water droplet that is
      suspended in oil in a sensor cavity. We tested the various geometrical and
      physical parameters of the impact sensor to identify their relations to threshold
      acceleration values. We show that the state diagram that is plotted against the
      dimensionless Archimedes and Bond numbers adequately describes the response of
      the proposed sensor.

PMID- 29634751
TI  - Correction: Safety and vaccine-induced HIV-1 immune responses in healthy
      volunteers following a late MVA-B boost 4 years after the last immunization.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0186602.].

PMID- 29634752
TI  - The effect of long chain polyunsaturated fatty acid supplementation on
      intelligence in low birth weight infant during lactation: A meta-analysis.
AB  - BACKGROUND: Low birth weight infant (LBWIs) are prone to mental and behavioural
      problems. As an important constituent of the brain and retina, long chain
      polyunsaturated fatty acids are essential for foetal infant mental and visual
      development. The effect of lactation supplemented with long chain polyunsaturated
      fatty acids (LCPUFA) on the improvement of intelligence in low birth weight
      children requires further validation. METHODS: In this study, a comprehensive
      search of multiple databases was performed to identify studies focused the
      association between intelligence and long chain polyunsaturated fatty acid
      supplementation in LBWIs. Studies that compared the Bayley Scales of Infant
      Development (BSID) or the Wechsler Abbreviated Scale of Intelligence for Children
      (WISC) scores between LBWIs who were supplemented and controls that were not
      supplemented with LCPUFA during lactation were selected for inclusion in the meta
      analysis. RESULTS: The main outcome was the mean difference in the mental
      development index (MDI) and psychomotor development index (PDI) of the BSID and
      the full scale intelligence quotient (FSIQ), verbal intelligence quotient (VIQ)
      and performance intelligence quotient (PIQ) of the WISC between LBWIs and
      controls. Our findings indicated that the mean BSID or WISC scores in LBWIs did
      not differ between the supplemented groups and controls. CONCLUSION: This meta
      analysis does not reveal that LCPUFA supplementation has a significant impact on
      the level of intelligence in LBWIs.

PMID- 29634753
TI  - Correction: DNA Sequence Variants in the Five Prime Untranslated Region of the
      Cyclooxygenase-2 Gene Are Commonly Found in Healthy Dogs and Gray Wolves.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0133127.].

PMID- 29634754
TI  - Leptospiral flagellar sheath protein FcpA interacts with FlaA2 and FlaB1 in
      Leptospira biflexa.
AB  - Leptospira spp. are spirochete bacteria that possess periplasmic flagella (PFs)
      underneath the outer membrane; each flagellum is attached to each end of the
      protoplasmic cylinder. PFs of Leptospira have a coiled shape that bends the end
      of the cell body. However, the molecular mechanism by which multiple flagellar
      proteins organize to form the distinctively curled PF of Leptospira remains
      unclear. Here we obtained a slow-motility mutant of L. biflexa MD4-3 by random
      insertion mutagenesis using a Himar1 transposon. In MD4-3, the gene encoding the
      flagellar sheath protein, flagellar-coiling protein A (FcpA), which was recently
      identified in L. interrogans, was inactivated. As with L. interrogans DeltafcpA
      strains, the L. biflexa DeltafcpA strain lacked a distinct curvature at both ends
      of the cell body, and its motility was significantly reduced as compared with
      that of the wild-type strain. PFs isolated from the DeltafcpA strain were
      straight and were thinner than those isolated from the wild-type strain. Western
      blot analysis revealed that flagellar proteins FlaA1, FlaA2, FlaB1, and FlaB2
      were expressed in the DeltafcpA strain but the flagellar proteins, except for
      FlaB2 were not incorporated in its PFs. Immunoprecipitation assay using anti-FcpA
      antiserum demonstrated that FcpA associates with FlaA2 and FlaB1. The association
      between FcpA and FlaA2 was also verified using pull-down assay. The regions of
      FlaA2 and FlaB1 interacting with FcpA were determined using a bacterial two
      hybrid assay. These results suggest that FcpA together with FlaA2, produces
      coiling of PF of the Leptospira, and the interaction between the sheath and core
      filament may be mediated by FcpA and FlaB1.

PMID- 29634756
TI  - Microalgal photophysiology and macronutrient distribution in summer sea ice in
      the Amundsen and Ross Seas, Antarctica.
AB  - Our study addresses how environmental variables, such as macronutrients
      concentrations, snow cover, carbonate chemistry and salinity affect the
      photophysiology and biomass of Antarctic sea-ice algae. We have measured vertical
      profiles of inorganic macronutrients (phosphate, nitrite + nitrate and silicic
      acid) in summer sea ice and photophysiology of ice algal assemblages in the
      poorly studied Amundsen and Ross Seas sectors of the Southern Ocean. Brine-scaled
      bacterial abundance, chl a and macronutrient concentrations were often high in
      the ice and positively correlated with each other. Analysis of photosystem II
      rapid light curves showed that microalgal cells in samples with high phosphate
      and nitrite + nitrate concentrations had reduced maximum relative electron
      transport rate and photosynthetic efficiency. We also observed strong couplings
      of PSII parameters to snow depth, ice thickness and brine salinity, which
      highlights a wide range of photoacclimation in Antarctic pack-ice algae. It is
      likely that the pack ice was in a post-bloom situation during the late sea-ice
      season, with low photosynthetic efficiency and a high degree of nutrient
      accumulation occurring in the ice. In order to predict how key biogeochemical
      processes are affected by future changes in sea ice cover, such as in situ
      photosynthesis and nutrient cycling, we need to understand how physicochemical
      properties of sea ice affect the microbial community. Our results support
      existing hypothesis about sea-ice algal photophysiology, and provide additional
      observations on high nutrient concentrations in sea ice that could influence the
      planktonic communities as the ice is retreating.

PMID- 29634755
TI  - Large scale newborn deafness genetic screening of 142,417 neonates in Wuhan,
      China.
AB  - Almost one third of the three million people in China suffering severe deafness
      are children, and 50% of these cases are believed to have genetic components to
      their etiology. Newborn hearing genetic screening can complement Universal
      Neonatal Hearing Screening for the diagnosis of congenital hearing loss as well
      as identifying children at risk for late-onset and progressive hearing
      impairment. The aim of this joint academic and Ministry of Health project was to
      prototype a cost effective newborn genetic screen in a community health setting
      on a city-wide level, and to ascertain the prevalence of variation at loci that
      have been associated with non-syndromic hearing loss. With the participation of
      143 local hospitals in the city of Wuhan, China we screened 142,417 neonates born
      between May 2014 and Dec. 2015. The variants GJB2 c.235delC, SLC26A4 c.919-2A>G,
      and mitochondrial variants m.1555A>G and m.1494C>T were assayed using real time
      PCR. Newborns found to carry a variant were re-assayed by sequencing in
      duplicate. Within a subset of 707 newborns we assayed using real-time PCR and
      ARMS-PCR to compare cost, sensitivity and operating procedure. The most frequent
      hearing loss associated allele detected in this population was the 235delC
      variant in GJB2 gene. In total, 4289 (3.01%) newborns were found to carry at
      least one allele of either GJB2 c.235delC, SLC26A4 c.919-2A>G or two assayed MT
      RNR1 variants. There was complete accordance between the real-time PCR and the
      ARMS PCR, though the real-time PCR had a much lower failure rate. Real-time PCR
      had a lower cost and operating time than ARMS PCR. Ongoing collaboration with the
      participating hospitals will determine the specificity and sensitivity of the
      association of the variants with hearing loss at birth and arising in early
      childhood, allowing an estimation of the benefits of newborn hearing genetic
      screening in a large-scale community setting.

PMID- 29634757
TI  - Predictability is attractive: Female preference for behaviourally consistent
      males but no preference for the level of male aggression in a bi-parental
      cichlid.
AB  - Although personality traits can largely affect individual fitness we know little
      about the evolutionary forces generating and maintaining personality variation.
      Here, we investigated the hypothesis that personality variation in aggression is
      sexually selected in the monogamous, bi-parental cichlid Pelvicachromis pulcher.
      In this species, breeding pairs form territories and they aggressively defend
      their territory and offspring against con- and heterospecific intruders. In our
      mate choice study, we followed up two alternative hypotheses. We either expected
      females to show a directional preference for a high level and high consistency of
      aggression (potentially indicating mate choice for male parental quality).
      Alternatively, we expected females to choose males for (dis-)similarity in the
      level/consistency of aggression (potentially indicating mate choice for
      compatibility). Individual level and consistency of aggression were assessed for
      males and females using mirror tests. After eavesdropping on aggressive behaviour
      of two males (differing in level and consistency of aggression) females were then
      allowed to choose between the two males. Males, but not females, showed
      personality variation in aggression. Further, females generally preferred
      consistent over inconsistent males independent of their level of aggression. We
      did not detect a general preference for the level of male aggression. However, we
      found an above average preference for consistent high-aggression males; whereas
      female preference for inconsistent high-aggression did not deviate from random
      choice. Our results suggest behavioural consistency of aggression in male rainbow
      kribs is selected for via female mate choice. Further, our study underlines the
      importance of considering both the level and the consistency of a behavioural
      trait in studies of animal behaviour.

PMID- 29634758
TI  - Zika virus infection in immunocompetent pregnant mice causes fetal damage and
      placental pathology in the absence of fetal infection.
AB  - Zika virus (ZIKV) infection during human pregnancy may cause diverse and serious
      congenital defects in the developing fetus. Previous efforts to generate animal
      models of human ZIKV infection and clinical symptoms often involved manipulating
      mice to impair their Type I interferon (IFN) signaling, thereby allowing enhanced
      infection and vertical transmission of virus to the embryo. Here, we show that
      even pregnant mice competent to generate Type I IFN responses that can limit ZIKV
      infection nonetheless develop profound placental pathology and high frequency of
      fetal demise. We consistently found that maternal ZIKV exposure led to placental
      pathology and that ZIKV RNA levels measured in maternal, placental or embryonic
      tissues were not predictive of the pathological effects seen in the embryos.
      Placental pathology included trophoblast hyperplasia in the labyrinth,
      trophoblast giant cell necrosis in the junctional zone, and loss of embryonic
      vessels. Our findings suggest that, in this context of limited infection,
      placental pathology rather than embryonic/fetal viral infection may be a stronger
      contributor to adverse pregnancy outcomes in mice. Our finding demonstrates that
      in immunocompetent mice, direct viral infection of the embryo is not essential
      for fetal demise. Our immunologically unmanipulated pregnancy mouse model
      provides a consistent and easily measurable congenital abnormality readout to
      assess fetal outcome, and may serve as an additional model to test prophylactic
      and therapeutic interventions to protect the fetus during pregnancy, and for
      studying the mechanisms of ZIKV congenital immunopathogenesis.

PMID- 29634759
TI  - Ribosome profiling uncovers selective mRNA translation associated with eIF2
      phosphorylation in erythroid progenitors.
AB  - The regulation of translation initiation factor 2 (eIF2) is important for
      erythroid survival and differentiation. Lack of iron, a critical component of
      heme and hemoglobin, activates Heme Regulated Inhibitor (HRI). This results in
      phosphorylation of eIF2 and reduced eIF2 availability, which inhibits protein
      synthesis. Translation of specific transcripts such as Atf4, however, is
      enhanced. Upstream open reading frames (uORFs) are key to this regulation. The
      aim of this study is to investigate how tunicamycin treatment, that induces eIF2
      phosphorylation, affects mRNA translation in erythroblasts. Ribosome profiling
      combined with RNA sequencing was used to determine translation initiation sites
      and ribosome density on individual transcripts. Treatment of erythroblasts with
      Tunicamycin (Tm) increased phosphorylation of eIF2 2-fold. At a false discovery
      rate of 1%, ribosome density was increased for 147 transcripts, among which
      transcriptional regulators such as Atf4, Tis7/Ifrd1, Pnrc2, Gtf2h, Mbd3, JunB and
      Kmt2e. Translation of 337 transcripts decreased more than average, among which
      Dym and Csde1. Ribosome profiling following Harringtonine treatment uncovered
      novel translation initiation sites and uORFs. Surprisingly, translated uORFs did
      not predict the sensitivity of transcripts to altered ribosome recruitment in
      presence or absence of Tm. The regulation of transcription and translation
      factors in reponse to eIF2 phosphorylation may explain the large overall response
      to iron deficiency in erythroblasts.

PMID- 29634760
TI  - High-resolution temporal and regional mapping of MAPT expression and splicing in
      human brain development.
AB  - The microtubule associated protein tau plays a critical role in the pathogenesis
      of neurodegenerative disease. Recent studies suggest that tau also plays a role
      in disorders of neuronal connectivity, including epilepsy and post-traumatic
      stress disorder. Animal studies have shown that the MAPT gene, which codes for
      the tau protein, undergoes complex pre-mRNA alternative splicing to produce
      multiple isoforms during brain development. Human data, particularly on temporal
      and regional variation in tau splicing during development are however lacking. In
      this study, we present the first detailed examination of the temporal and
      regional sequence of MAPT alternative splicing in the developing human brain. We
      used a novel computational analysis of large transcriptomic datasets (total n =
      502 patients), quantitative polymerase chain reaction (qPCR) and western blotting
      to examine tau expression and splicing in post-mortem human fetal, pediatric and
      adult brains. We found that MAPT exons 2 and 10 undergo abrupt shifts in
      expression during the perinatal period that are unique in the canonical human
      microtubule-associated protein family, while exon 3 showed small but significant
      temporal variation. Tau isoform expression may be a marker of neuronal
      maturation, temporally correlated with the onset of axonal growth. Immature brain
      regions such as the ganglionic eminence and rhombic lip had very low tau
      expression, but within more mature regions, there was little variation in tau
      expression or splicing. We thus demonstrate an abrupt, evolutionarily conserved
      shift in tau isoform expression during the human perinatal period that may be due
      to tau expression in maturing neurons. Alternative splicing of the MAPT pre-mRNA
      may play a vital role in normal brain development across multiple species and
      provides a basis for future investigations into the developmental and
      pathological functions of the tau protein.

PMID- 29634762
TI  - Correction: Evidence of embodied social competence during conversation in high
      functioning children with autism spectrum disorder.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0193906.].

PMID- 29634761
TI  - CtGEM typing: Discrimination of Chlamydia trachomatis ocular and urogenital
      strains and major evolutionary lineages by high resolution melting analysis of
      two amplified DNA fragments.
AB  - Chlamydia trachomatis infects the urogenital tract (UGT) and eyes. Anatomical
      tropism is correlated with variation in the major outer membrane protein encoded
      by ompA. Strains possessing the ocular ompA variants A, B, Ba and C are typically
      found within the phylogenetically coherent "classical ocular lineage". However,
      variants B, Ba and C have also been found within three distinct strains in
      Australia, all associated with ocular disease in children and outside the
      classical ocular lineage. CtGEM genotyping is a method for detecting and
      discriminating ocular strains and also the major phylogenetic lineages. The
      rationale was facilitation of surveillance to inform responses to C. trachomatis
      detection in UGT specimens from young children. CtGEM typing is based on high
      resolution melting analysis (HRMA) of two PCR amplified fragments with high
      combinatorial resolving power, as defined by computerised comparison of 65 whole
      genomes. One fragment is from the hypothetical gene defined by Jali-1891 in the
      C. trachomatis B_Jali20 genome, while the other is from ompA. Twenty
      combinatorial CtGEM types have been shown to exist, and these encompass unique
      genotypes for all known ocular strains, and also delineate the TI and T2 major
      phylogenetic lineages, identify LGV strains and provide additional resolution
      beyond this. CtGEM typing and Sanger sequencing were compared with 42 C.
      trachomatis positive clinical specimens, and there were no disjunctions. CtGEM
      typing is a highly efficient method designed and tested using large scale
      comparative genomics. It divides C. trachomatis into clinically and biologically
      meaningful groups, and may have broad application in surveillance.

PMID- 29634763
TI  - Correction: Survival from alcoholic hepatitis has not improved over time.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0192393.].

PMID- 29634764
TI  - Photochemical degradation of trypan blue.
AB  - PURPOSE: To investigate the photochemical degradation of trypan blue (TB) and to
      identify decomposition products. METHODS: Defined solution samples of TB and a
      mixture with lutein/zeaxanthin were exposed to blue light. Thermal degradation
      processes were ruled out using controls not subjected to irradiation. All samples
      were analyzed using optical microscopy, UV/Vis spectroscopy, matrix-assisted
      laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry and
      nuclear magnetic resonance (NMR) spectrometry. Degradation kinetics were
      determined based on changes in absorbance; intermediates were identified by
      analyzing mass differences of characteristic fragment ion peaks within the
      fragmentation patterns, and assignments were verified by NMR. RESULTS: TB
      demonstrated a photochemical degradation, which can be triggered by
      lutein/zeaxanthin. Intermediates vary depending on the presence of
      lutein/zeaxanthin. The self-sensitized photodegradation of TB occurs under
      generation of dimethyl sulfate and presumed formation of phenol. In contrast,
      within the presence of lutein/zeaxanthin the decomposition of TB indicates the
      formation of methoxyamine and sulfonyl arin. Thermal degradation processes were
      not observed. CONCLUSIONS: TB demonstrated a photodegradation that may be
      triggered by lutein/zeaxanthin and results in the formation of cytotoxic
      decomposition products. Our findings contribute to understand degradation
      mechanisms of TB and may elucidate previous clinical and experimental
      observations of cellular toxicity after TB application.

PMID- 29634765
TI  - Correction: Excess mortality and hospitalizations in transitional-age youths with
      a long-term disease: A national population-based cohort study.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0193729.].

PMID- 29634766
TI  - Anti-inflammatory, antiproliferative and cytoprotective potential of the Attalea
      phalerata Mart. ex Spreng. pulp oil.
AB  - The anti-inflammatory, antiproliferative and cytoprotective activity of the
      Attalea phalerata Mart. ex Spreng pulp oil was evaluated by in vitro and in vivo
      methods. As for the chemical profile, the antioxidant activity was performed by
      spectrophotometry, and the profile of carotenoids and amino acids by
      chromatography. Our data demonstrated that A. phalerata oil has high carotenoid
      content, antioxidant activity and the presence of 5 essential amino acids. In the
      in vitro models of inflammation, the oil demonstrated the capacity to inhibit
      COX1 and COX2 enzymes, the production of nitric oxide and also induces
      macrophages to spreading. In the in vivo models of inflammation, the oil
      inhibited edema and leukocyte migration in the Wistar rats. In the in vitro model
      of antiproliferative and cytoprotective activity, the oil was shown inactive
      against the kidney carcinoma and prostate carcinoma lineage cells and with
      cytoprotective capacity in murine fibroblast cells, inhibiting the cytotoxic
      action of doxorubicin. Therefore, it is concluded that A. phalerata pulp oil has
      anti-inflammatory effects with nutraceutical properties potential due to the rich
      composition. Moreover, the oil also has cytoprotective activity probably because
      of its ability to inhibit the action of free radicals.

PMID- 29634767
TI  - Frailty in a racially and socioeconomically diverse sample of middle-aged
      Americans in Baltimore.
AB  - Frailty is a risk factor for disability and mortality, and is more prevalent
      among African American (AA) elderly than whites. We examine frailty in middle
      aged racially and economically diverse adults, and investigate how race, poverty
      and frailty are associated with mortality. Data were from 2541 participants in
      the Healthy Aging in Neighborhoods of Diversity across the Life Span study in
      Baltimore, Maryland; 35-64 years old at initial assessment (56% women; 58% AA).
      Frailty was assessed using a modified FRAIL scale of fatigue, resistance,
      ambulation, illness and weight loss, and compared with difficulties in physical
      functioning and daily activities. Frailty prevalence was calculated across race
      and age groups, and associations with survival were assessed by Cox Regression.
      278 participants were frail (11%); 924 pre-frail (36%); 1339 not frail (53%). For
      those aged 45-54, a higher proportion of whites (13%) than AAs (8%) were frail;
      while the proportions were similar for those 55-64 (14%,16%). Frailty was
      associated with overall survival with an average follow-up of 6.6 years,
      independent of race, sex and poverty status (HR = 2.30; 95%CI 1.67-3.18). In this
      sample of economically and racially diverse older adults, the known association
      of frailty prevalence and age differed across race with whites having higher
      prevalence at younger ages. Frailty was associated with survival beyond the risk
      factors of race and poverty status in this middle-aged group. Early recognition
      of frailty at these younger ages may provide an effective method for preventing
      or delaying disabilities.

PMID- 29634768
TI  - Health-related quality of life and related factors in stroke survivors: Data from
      Korea National Health and Nutrition Examination Survey (KNHANES) 2008 to 2014.
AB  - As persons with stroke are surviving longer, monitoring and managing their
      quality of life is becoming important. We reviewed the Korea National Health and
      Nutrition Examination Survey (KNHANES) in order to evaluate the health-related
      quality of life (HRQoL) in stroke survivors as measured by the Euro Quality of
      Life-5D (EQ-5D), and to find out influencing factors. A total of 42,500 subjects
      were enrolled in the KNHANES, and 575 of them were persons with stroke. The EQ-5D
      index was lower in persons with stroke than those without stroke, when adjusted
      for age and sex (with stroke: 0.757+/-0.012, without stroke: 0.948+/-0.001, p <
      .0001). Dimension-specific influencing factors of HRQoL were observed in persons
      with stroke; mobility problems increased with old age; self-care problems
      increased with old age and depression; usual activity problems increased with old
      age, low income, absence of economic activity, and depression; pain/discomfort
      problems increased with low income. The EQ-5D index was lower in stroke survivors
      with older age, hypertension, diabetes mellitus, and lack of regular exercise.
      This is the first study to utilize nationally representative data of the Korean
      population to investigate the effect of stroke on HRQoL and explore the dimension
      specific influencing factors. Further development of rehabilitative interventions
      for post-stroke depression, vocational rehabilitation, and tailored programs for
      encouraging physical activity may be needed to improve the HRQoL in Korean stroke
      survivors.

PMID- 29634769
TI  - Antioxidant capacity of phenolics in Camellia nitidissima Chi flowers and their
      identification by HPLC Triple TOF MS/MS.
AB  - Camellia nitidissima Chi (CNC) is a valuable medicinal and edible plant in China.
      In this study, CNC flowers were extracted with 95% ethanol, then partitioned into
      dichloromethane, ethyl acetate, n-butanol, and water fractions, with the
      antioxidant capacity of flavonoids and other phytochemicals in CNC flowers
      investigated for the first time. Results showed that the ethyl acetate fraction
      exhibited the strongest antioxidant capacity and highest total phenolic content
      (TPC) compared with the other fractions. Furthermore, in the ethyl acetate
      fraction, the 50% effective concentrations (EC50) of ABTS+ and DPPH radical
      scavenging activities were 64.24 +/- 1.80 and 78.80 +/- 0.34 MUg/mL,
      respectively, and the ferric reducing antioxidant power (FRAP) was 801.49 +/-
      2.30 MUM FeSO4 at 1,000 MUg/mL. Pearson's correlation coefficients and principal
      component analyses (PCA) for the TPC and antioxidant capacity of the five
      fractions indicated that the phenolic compounds were the major antioxidant
      constituents in the flowers. To exploit the antioxidants in CNC flowers, 21
      phenolic compounds in the ethanolic extract fraction were identified by HPLC
      Triple TOF MS/MS, next, 12 flavonoids were isolated and elucidated, of which
      compounds 1-5 showed potent antioxidant capacity. In addition, the potential
      structure-activity relationship among these 12 flavonoids showed that (1) the o
      catechol group in the B-ring was primarily responsible for the antioxidant
      capacity of flavonoids and (2) steric hindrance, produced by glycosides and other
      groups, could reduce the antioxidant capacity of the flavonoids.

PMID- 29634770
TI  - Sesamin from Cuscuta palaestina natural plant extracts: Directions for new
      prospective applications.
AB  - The aim of this study is to disclose the potential bioactive components of
      Cuscuta palaestina, a native parasitic natural plant of flora palaestina and to
      open direction towards new prospective application. GC-MS analysis identified 18
      components in the methanolic extract of C. palaestina for the first time. The
      most appealing among them are Sesamin and two other phytosterols (Campesterol and
      Stigmasterol), all of which are documented in the scientific literature for their
      anticancer activity. Quantitation of Sesamin extracted from C. palaestina by HPLC
      PDA with the use of three organic solvents showed that the Sesamin content in the
      methanolic extract was the highest. Following the disclosure of Sesamin presence
      in C. palaestina, we raised the question of whether it is produced naturally in
      C. palaestina or acquired from the host plant. The quantitation of Sesamin in C.
      palaestina was performed while being with five different host plants, and was
      compared with the amount of Sesamin in C. palaestina grown alone. The findings
      reveal that Sesamin is an endogenous secondary metabolite in C. palaestina. Thus,
      further studies are required to prove if C. palaestina can be used as an
      alternative source of anticancer phytochemicals, mainly Sesamin, and if proteins
      in the Sesamin production pathway could be valid biological targets for the
      development of novel and selective pesticides for control/ eradication of C.
      palaestina and maybe some other Cuscuta species. As well, the findings from this
      study raise a big question of whether inferring Sesamin production in C.
      palaestina could reduce its attack ability to host plants.

PMID- 29634771
TI  - Chronic hepatitis B virus and liver fibrosis: A mathematical model.
AB  - Hepatitis B virus (HBV) infection is a liver disorder that can result in
      cirrhosis, liver failure and hepatocellular carcinoma. HBV infection remains a
      major global health problem, as it affects more 350 million people chronically
      and kills roughly 600,000 people annually. Drugs currently used against HBV
      include IFN-alpha that decreases viremia, inflammation and the growth of liver
      fibrosis, and adefovir that decreases the viral load. Each of these drugs can
      have severe side-effects. In the present paper, we consider the treatment of
      chronic HBV by a combination of IFN-alpha and adefovir, and raise the following
      question: What should be the optimal ratio between IFN-alpha and adefovir in
      order to achieve the best 'efficacy' under constraints on the total amount of the
      drugs; here the efficacy is measured by the reduction of the levels of
      inflammation and of fibrosis? We develop a mathematical model of HBV pathogenesis
      by a system of partial differential equations (PDEs) and use the model to
      simulate a 'synergy map' which addresses the above question.

PMID- 29634772
TI  - Linking private, for-profit providers to public sector services for HIV and
      tuberculosis co-infected patients: A systematic review.
AB  - BACKGROUND: Tuberculosis (TB) is the leading cause of infectious disease deaths
      worldwide and is the leading cause of death among people with HIV. The World
      Health Organization (WHO) has called for collaboration between public and private
      healthcare providers to maximize integration of TB/HIV services and minimize
      costs. We systematically reviewed published models of public-private sector
      diagnostic and referral services for TB/HIV co-infected patients. METHODS: We
      searched PubMed, the Cochrane Central Register of Controlled Trials, Google
      Scholar, Science Direct, CINAHL and Web of Science. We included studies that
      discussed programs that linked private and public providers for TB/HIV concurrent
      diagnostic and referral services and used Review Manager (Version 5.3, 2015) for
      meta-analysis. RESULTS: We found 1,218 unduplicated potentially relevant articles
      and abstracts; three met our eligibility criteria. All three described public
      private TB/HIV diagnostic/referral services with varying degrees of integration.
      In Kenya private practitioners were able to test for both TB and HIV and offer
      state-subsidized TB medication, but they could not provide state-subsidized
      antiretroviral therapy (ART) to co-infected patients. In India private
      practitioners not contractually engaged with the public sector offered TB/HIV
      services inconsistently and on a subjective basis. Those partnered with the
      state, however, could test for both TB and HIV and offer state-subsidized
      medications. In Nigeria some private providers had access to both state
      subsidized medications and diagnostic tests; others required patients to pay out
      of-pocket for testing and/or treatment. In a meta-analysis of the two
      quantitative reports, TB patients who sought care in the public sector were
      almost twice as likely to have been tested for HIV than TB patients who sought
      care in the private sector (risk ratio [RR] 1.98, 95% confidence interval [CI]
      1.88-2.08). However, HIV-infected TB patients who sought care in the public
      sector were marginally less likely to initiate ART than TB patients who sought
      care from private providers (RR 0.89, 95% CI 0.78-1.03). CONCLUSION: These three
      studies are examples of public-private TB/HIV service delivery and can
      potentially serve as models for integrated TB/HIV care systems. Successful public
      private diagnostic and treatment services can both improve outcomes and decrease
      costs for patients co-infected with HIV and TB.

PMID- 29634773
TI  - Acidic pH triggers the phosphorylation of the response regulator NtrX in
      alphaproteobacteria.
AB  - Many signaling pathways that control cellular development, cell-cycle progression
      and nutritional versatility have been studied in Caulobacter crescentus. For
      example, it was suggested that the response regulator NtrX is conditionally
      essential for this bacterium and that it might be necessary for responding to a
      signal produced in phosphate-replete minimal medium. However, such signal has not
      been identified yet and the role of NtrX in C. crescentus biology remains
      elusive. Here, using wild-type C. crescentus and a strain with a chromosomally
      myc-tagged ntrX gene, we demonstrate that high concentrations of phosphate (10
      mM) regulate ntrX transcription and the abundance of the protein. We also show
      that the pH of the medium acts as a switch able to regulate the phosphorylation
      status of NtrX, promoting its phosphorylation under mildly acidic conditions and
      its dephosphorylation at neutral pH. Moreover, we demonstrate that the ntrX gene
      is required for survival in environments with low pH and under acidic stress.
      Finally, we prove that NtrX phosphorylation is also triggered by low pH in
      Brucella abortus, a pathogenic alphaproteobacterium. Overall, our work
      contributes to deepen the general knowledge of this system and provides tools to
      elucidate the NtrX regulon.

PMID- 29634774
TI  - Dimeric IgG complexes from IVIg are incapable of inducing in vitro neutrophil
      degranulation or complement activation.
AB  - PURPOSE: Intravenous immunoglobulin (IVIg) products contain various amounts of
      dimeric IgG complexes. Current insights into the possible biological activities
      of these dimers remain controversial, and both immunemodulating and immune
      activating effects have been reported. Here, we analyzed the putative immune
      activating effects of dimers isolated from IVIg. METHODS: Dimers isolated from
      IVIg were purified by high-performance size-exclusion chromatography (HP-SEC) and
      tested for the ability to induce neutrophil degranulation in vitro. RESULTS:
      Dimers isolated from IVIg were found to be incapable of inducing in vitro
      neutrophil degranulation or complement activation, even at concentrations
      exceeding those expected to be reached upon administration in patients. These
      results depend on the removal of artefactual activation by using 0.1 micron
      filtration and the use of poloxamer to prevent adsorption of IgG onto the solid
      phase. CONCLUSIONS: The data suggest dimeric IgG found in IVIg may bind to Fc
      receptors without causing activation.

PMID- 29634775
TI  - Zinc is an inhibitor of the LdtR transcriptional activator.
AB  - LdtR is a master regulator of gene expression in Liberibacter asiaticus, one of
      the causative agents of citrus greening disease. LdtR belongs to the MarR-family
      of transcriptional regulators and it has been linked to the regulation of more
      than 180 genes in Liberibacter species, most of them gathered in the following
      Clusters of Orthologous Groups: cell motility, cell wall envelope, energy
      production, and transcription. Our previous transcriptomic evidence suggested
      that LdtR is directly involved in the modulation of the zinc uptake system genes
      (znu) in the closely related L. crescens. In this report, we show that LdtR is
      involved in the regulation of one of the two encoded zinc uptake mechanisms in L.
      asiaticus, named znu2. We also show that LdtR binds zinc with higher affinity
      than benzbromarone, a synthetic effector inhibitory molecule, resulting in the
      disruption of the LdtR:promoter interactions. Using site-directed mutagenesis,
      electrophoretic mobility shift assays (EMSAs), and isothermal titration
      calorimetry, we identified that residues C28 and T43 in LdtR, located in close
      proximity to the Benz1 pocket, are involved in the interaction with zinc. These
      results provided new evidence of a high-affinity effector molecule targeting a
      key player in L. asiaticus' physiology and complemented our previous findings
      about the mechanisms of signal transduction in members of the MarR-family.

PMID- 29634777
TI  - Genetic modification of Anopheles stephensi for resistance to multiple Plasmodium
      falciparum strains does not influence susceptibility to o'nyong'nyong virus or
      insecticides, or Wolbachia-mediated resistance to the malaria parasite.
AB  - Mosquitoes that have been genetically engineered for resistance to human
      pathogens are a potential new tool for controlling vector-borne disease. However,
      genetic modification may have unintended off-target effects that could affect the
      mosquitoes' utility for disease control. We measured the resistance of five
      genetically modified Plasmodium-suppressing Anopheles stephensi lines to
      o'nyong'nyong virus, four classes of insecticides, and diverse Plasmodium
      falciparum field isolates and characterized the interactions between our genetic
      modifications and infection with the bacterium Wolbachia. The genetic
      modifications did not alter the mosquitoes' resistance to either o'nyong'nyong
      virus or insecticides, and the mosquitoes were equally resistant to all tested P.
      falciparum strains, regardless of Wolbachia infection status. These results
      indicate that mosquitoes can be genetically modified for resistance to malaria
      parasite infection and remain compatible with other vector-control measures
      without becoming better vectors for other pathogens.

PMID- 29634776
TI  - Severe abnormal Heart Rate Turbulence Onset is associated with deterioration of
      liver cirrhosis.
AB  - BACKGROUND: In patients with liver cirrhosis, cardiac dysfunction is frequent and
      is associated with increased morbidity and mortality. Cardiac dysfunction in
      cirrhosis seems to be linked to autonomic dysfunction. This study investigates
      the role of autonomic dysfunction assessed by Heart Rate Turbulence (HRT)
      analyses in patients with liver cirrhosis. METHODS AND PATIENTS: Inclusion
      criteria was (1) diagnosis of cirrhosis by clinical, imaging or biopsy and (2)
      evaluation by standard 12-lead-ECG and 24h holter monitoring and (3) at least 3
      premature ventricular contractions. The exclusion criterion was presence of
      cardiac diseases, independent of liver cirrhosis. Biochemical parameters were
      analysed using standard methods. HRT was assessed using Turbulence onset (TO) and
      slope (TS). The endpoint was deterioration of liver cirrhosis defined as
      increased MELD and readmission for complications of liver cirrhosis. RESULTS: Out
      of 122 cirrhotic patients, 82 patients (63% male) with median Child score of 6
      (range 5-12) and median MELD score of 10 (range 6-32) were included. Increasing
      Child score, INR and decreasing albumin were correlated with TO. In addition,
      decompensated patients with ascites showed more abnormal TO and TS. During the
      observation period, patients with more abnormal TO showed significantly higher
      rate of rising MELD Score at 6 months (p = 0.03). Nevertheless, at least in our
      collective HRT-parameters were not independent predictors of deterioration of
      cirrhosis. CONCLUSION: Parameters of HRT are closely associated with
      deterioration of cirrhosis and might be helpful in its prediction.

PMID- 29634778
TI  - Changes in maize transcriptome in response to maize Iranian mosaic virus
      infection.
AB  - BACKGROUND: Maize Iranian mosaic virus (MIMV, genus Nucleorhabdovirus, family
      Rhabdoviridae) causes an economically important disease in maize and other
      gramineous crops in Iran. MIMV negative-sense RNA genome sequence of 12,426
      nucleotides has recently been completed. Maize Genetics and Genomics database
      shows that 39,498 coding genes and 4,976 non-coding genes of maize have been
      determined, but still some transcripts could not be annotated. The molecular host
      cell responses of maize to MIMV infection including differential gene expression
      have so far not been elucidated. METHODOLOGY/PRINCIPAL FINDINGS: Complementary
      DNA libraries were prepared from total RNA of MIMV-infected and mock-inoculated
      maize leaves and sequenced using Illumina HiSeq 2500. Cleaned raw transcript
      reads from MIMV-infected maize were mapped to reads from uninfected maize and to
      a maize reference genome. Differentially expressed transcripts were characterized
      by gene ontology and biochemical pathway analyses. Transcriptome data for
      selected genes were validated by real-time quantitative PCR.
      CONCLUSION/SIGNIFICANCE: Approximately 42 million clean reads for each treatment
      were obtained. In MIMV-infected maize compared to uninfected plants, 1689
      transcripts were up-regulated and 213 transcripts were down-regulated. In
      response to MIMV infection, several pathways were activated in maize including
      immune receptor signaling, metabolic pathways, RNA silencing, hormone-mediated
      pathways, protein degradation, protein kinase and ATP binding activity, and fatty
      acid metabolism. Also, several transcripts including those encoding hydrophobic
      protein RCI2B, adenosylmethionine decarboxylase NAC transcription factor and
      nucleic acid binding, leucine-rich repeat, heat shock protein, 26S proteasome,
      oxidoreductases and endonuclease activity protein were up-regulated. These data
      will contribute to the identification of genes and pathways involved in plant
      virus interactions that may serve as future targets for improved disease control.

PMID- 29634779
TI  - Improvement of the reduction in catastrophic health expenditure in China's public
      health insurance.
AB  - This study aimed to locate the contributing factors of Catastrophic Health
      Expenditure (CHE), evaluate their impacts, and try to propose strategies for
      reducing the possibilities of CHE in the context of China's current public health
      insurance system. The financial data of all hospitalization cases from a sample
      hospital in 2013 were gathered and used to determine the pattern of household
      medical costs. A simulation model was constructed based on China's current public
      health insurance system to evaluate the financial burden for medical service on
      Chinese patients, as well as to calculate the possibilities of CHE. Then, by
      adjusting several parameters, suggestions were made for China's health insurance
      system in order to reduce CHE. It's found with China's current public health
      insurance system, the financial aid that a patient may receive depends on whether
      he is from an urban or rural area and whether he is employed. Due to the
      different insurance policies and the wide income gap between urban and rural
      areas, rural residents are much more financially vulnerable during health crisis.
      The possibility of CHE can be more than 50% for low-income rural families. The
      CHE ratio can be dramatically lowered by applying different policies for
      different household income groups. It's concluded the financial burden for
      medical services of Chinese patients is quite large currently, especially for
      those from rural areas. By referencing different healthcare policies in the
      world, applying different health insurance policies for different income groups
      can dramatically reduce the possibility of CHE in China.

PMID- 29634780
TI  - Proteomic analysis of human epileptic neocortex predicts vascular and glial
      changes in epileptic regions.
AB  - Epilepsy is a common neurological disorder, which is not well understood at the
      molecular level. Exactly why some brain regions produce epileptic discharges and
      others do not is not known. Patients who fail to respond to antiseizure
      medication (refractory epilepsy) can benefit from surgical removal of brain
      regions to reduce seizure frequency. The tissue removed in these surgeries offers
      an invaluable resource to uncover the molecular and cellular basis of human
      epilepsy. Here, we report a proteomic study to determine whether there are common
      proteomic patterns in human brain regions that produce epileptic discharges. We
      analyzed human brain samples, as part of the Systems Biology of Epilepsy Project
      (SBEP). These brain pieces are in vivo electrophysiologically characterized human
      brain samples withdrawn from the neocortex of six patients with refractory
      epilepsy. This study is unique in that for each of these six patients the
      comparison of protein expression was made within the same patient: a more
      epileptic region was compared to a less epileptic brain region. The amount of
      epileptic activity was defined for each patient as the frequency of their
      interictal spikes (electric activity between seizures that is a parameter
      strongly linked to epilepsy). Proteins were resolved from three subcellular
      fractions, using a 2D differential gel electrophoresis (2D-DIGE), revealing 31
      identified protein spots that changed significantly. Interestingly, glial
      fibrillary acidic protein (GFAP) was found to be consistently down regulated in
      high spiking brain tissue and showed a strong negative correlation with spike
      frequency. We also developed a two-step analysis method to select for protein
      species that changed frequently among the patients and identified these proteins.
      A total of 397 protein spots of interest (SOI) were clustered by protein
      expression patterns across all samples. These clusters were used as markers and
      this analysis predicted proteomic changes due to both histological differences
      and molecular pathways, revealed by examination of gene ontology clusters. Our
      experimental design and proteomic data analysis predicts novel glial changes,
      increased angiogenesis, and changes in cytoskeleton and neuronal projections
      between high and low interictal spiking regions. Quantitative histological
      staining of these same tissues for both the vascular and glial changes confirmed
      these findings, which provide new insights into the structural and functional
      basis of neocortical epilepsy.

PMID- 29634781
TI  - The association between serum vitamin D levels and renal tubular dysfunction in a
      general population exposed to cadmium in China.
AB  - Cadmium exposure can cause renal tubular dysfunction. Recent studies show that
      vitamin D can play multiple roles in the body. However, the association between
      serum vitamin D levels and renal tubular dysfunction in a general population
      exposed to cadmium has not been clarified. We performed study to assess the
      effects of cadmium on serum 25(OH) D levels and the association between serum
      25(OH) D levels and renal tubular dysfunction in a population environmentally
      exposed to cadmium. A total of 133 subjects living in control area and two
      cadmium polluted areas were included in the present study. Cadmium in urine (UCd)
      and blood (BCd), urinary beta2Microglobulin (UBMG), urinary retinol binding
      protein (URBP) and serum 25 (OH) D were determined. Logistic regression was used
      to estimate the association between 25 (OH) D and prevalence of renal tubular
      dysfunction. No significant differences were observed in serum 25(OH) D levels
      among the four quartile of UCd and BCd after adjusting with cofounders. After
      adjusted with the confounders, the odds ratio (OR) of subjects with 25(OH) D >=
      40 ng/ml were 0.20 (95%CI: 0.1-0.8) if UBMG was chosen as indicators of renal
      dysfunction and 0.28 (95%CI: 0.1-1.1) if URBP was chosen as indicators of renal
      dysfunction, compared with those with 25(OH) D < 30 ng/ml, respectively. Similar
      results were observed in those subjects living in cadmium polluted areas or with
      high level of UCd or BCd. Our data indicated that cadmium exposure did not affect
      serum 25(OH) D level and high 25 (OH) D levels were associated with a decreased
      risk of renal tubular dysfunction induced by cadmium.

PMID- 29634782
TI  - Core lipid, surface lipid and apolipoprotein composition analysis of lipoprotein
      particles as a function of particle size in one workflow integrating asymmetric
      flow field-flow fractionation and liquid chromatography-tandem mass spectrometry.
AB  - Lipoproteins are complex molecular assemblies that are key participants in the
      intricate cascade of extracellular lipid metabolism with important consequences
      in the formation of atherosclerotic lesions and the development of cardiovascular
      disease. Multiplexed mass spectrometry (MS) techniques have substantially
      improved the ability to characterize the composition of lipoproteins. However,
      these advanced MS techniques are limited by traditional pre-analytical
      fractionation techniques that compromise the structural integrity of lipoprotein
      particles during separation from serum or plasma. In this work, we applied a
      highly effective and gentle hydrodynamic size based fractionation technique,
      asymmetric flow field-flow fractionation (AF4), and integrated it into a
      comprehensive tandem mass spectrometry based workflow that was used for the
      measurement of apolipoproteins (apos A-I, A-II, A-IV, B, C-I, C-II, C-III and E),
      free cholesterol (FC), cholesterol esters (CE), triglycerides (TG), and
      phospholipids (PL) (phosphatidylcholine (PC), sphingomyelin (SM),
      phosphatidylethanolamine (PE), phosphatidylinositol (PI) and
      lysophosphatidylcholine (LPC)). Hydrodynamic size in each of 40 size fractions
      separated by AF4 was measured by dynamic light scattering. Measuring all major
      lipids and apolipoproteins in each size fraction and in the whole serum, using
      total of 0.1 ml, allowed the volumetric calculation of lipoprotein particle
      numbers and expression of composition in molar analyte per particle number
      ratios. Measurements in 110 serum samples showed substantive differences between
      size fractions of HDL and LDL. Lipoprotein composition within size fractions was
      expressed in molar ratios of analytes (A-I/A-II, C-II/C-I, C-II/C-III. E/C-III,
      FC/PL, SM/PL, PE/PL, and PI/PL), showing differences in sample categories with
      combinations of normal and high levels of Total-C and/or Total-TG. The agreement
      with previous studies indirectly validates the AF4-LC-MS/MS approach and
      demonstrates the potential of this workflow for characterization of lipoprotein
      composition in clinical studies using small volumes of archived frozen samples.

PMID- 29634783
TI  - The gamma33 subunit of R-phycoerythrin from Gracilaria chilensis has a typical
      double linked phycourobilin similar to beta subunit.
AB  - Phycobilisomes (PBS) are accessory light harvesting protein complexes formed
      mainly by phycobiliproteins (PBPs). The PBPs absorb light that is efficiently
      transferred to Photosystems due to chromophores covalently bound to specific
      cysteine residues. Besides phycobiliproteins (PE), the PBS contains linker
      proteins responsible for assembly and stabilization of the whole complex and the
      tuning of energy transfer steps between chromophores. The linker (gamma33) from
      Gracilaria chilensis, is a chromophorylated rod linker associated to (alphabeta)6
      hexamers of R-phycoerythrin (R-PE). Its role in the energy transfer process is
      not clear yet. Structural studies as well as the composition and location of the
      chromophores are essential to understand their involvement in the energy transfer
      process in PBS. To achieve this, the coding gene of gamma33 was cloned and
      sequenced. The sequence was analyzed by informatics tools, to obtain preliminary
      information which leaded the next experiments. The protein was purified from R
      phycoerythrin, and the sequence confirmed by mass spectrometry. The coding
      sequence analysis revealed a protein of 318 aminoacid residues containing a
      chloroplastidial transit peptide (cTP) of 39 aminoacids at the N-terminus. The
      conservation of cysteines revealed possible chromophorylation sites. Using alpha
      and beta R-PE subunits as spectroscopic probes in denaturation assays, we deduced
      a double bonded phycourobilin (PUB) on gamma33 subunit that were confirmed
      between Cys62 and Cys73 (DL-PUB62/73) by mass spectrometry. The cysteines
      involved in the double link are located in a helical region, in a conformation
      that reminds the position of the DL-PUB50/61 in the beta subunit of R-PE. The
      position of single linked PUB at Cys95 and a single linked PEB at Cys172 were
      also confirmed. Spectroscopic studies show the presence of both types of
      chromophores and that there are not energy transfer by FRET among them.

PMID- 29634784
TI  - The role of the C-domain of bacteriophage T4 gene 32 protein in ssDNA binding and
      dsDNA helix-destabilization: Kinetic, single-molecule, and cross-linking studies.
AB  - The model single-stranded DNA binding protein of bacteriophage T4, gene 32
      protein (gp32) has well-established roles in DNA replication, recombination, and
      repair. gp32 is a single-chain polypeptide consisting of three domains. Based on
      thermodynamics and kinetics measurements, we have proposed that gp32 can undergo
      a conformational change where the acidic C-terminal domain binds internally to or
      near the single-stranded (ss) DNA binding surface in the core (central) domain,
      blocking ssDNA interaction. To test this model, we have employed a variety of
      experimental approaches and gp32 variants to characterize this conformational
      change. Utilizing stopped-flow methods, the association kinetics of wild type and
      truncated forms of gp32 with ssDNA were measured. When the C-domain is present,
      the log-log plot of k vs. [NaCl] shows a positive slope, whereas when it is
      absent (*I protein), there is little rate change with salt concentration, as
      expected for this model.A gp32 variant lacking residues 292-296 within the C
      domain, DeltaPR201, displays kinetic properties intermediate between gp32 and *I.
      The single molecule force-induced DNA helix-destabilizing activitiesas well as
      the single- and double-stranded DNA affinities of DeltaPR201 and gp32 truncated
      at residue 295 also fall between full-length protein and *I. Finally, chemical
      cross-linking of recombinant C-domain and gp32 lacking both N- and C-terminal
      domains is inhibited by increasing concentrations of a short single-stranded
      oligonucleotide, and the salt dependence of cross-linking mirrors that expected
      for the model. Taken together, these results provide the first evidence in
      support of this model that have been obtained through structural probes.

PMID- 29634785
TI  - Optimization of alkaline extraction of hemicellulose from sweet sorghum bagasse
      and its direct application for the production of acidic xylooligosaccharides by
      Bacillus subtilis strain MR44.
AB  - As predominant components of hemicelluloses in grasses,
      methylglucuroarabinoxylans (MeGAXn) are sources for the production of acidic
      xylooligosaccharides (U-XOS). Bacillus subtilis MR44, an engineered biocatalyst
      to secrete only the XynC xylanase and Axh43 arabinoxylan hydrolase is capable of
      processing MeGAXn to exclusively U-XOS. The present studies are directed at the
      explosion on direct alkaline extraction serving for production of U-XOS. Response
      Surface Methodology was used to optimize xylan extraction conditions on the sweet
      sorghum bagasse to achieve maximum hemicelluloses yield. The optimized condition
      was as follows: extraction time of 3.91 h, extraction temperature of 86.1 degrees
      C, and NaOH concentration (w/w) of 12.33%. Crude xylan extracted with NaOH
      revealed a compositional analysis of xylose (79.0%), arabinose (5.3%), glucose
      (1.7%), lignin and ash (5.6%). After neutralization this xylan preparation
      supported growth of MR44, processing MeGAXn from sweet sorghum and accumulating U
      XOS. The quality of U-XOS produced by MR44 using alkaline-treated sweet sorghum
      bagasse was comparable to that obtained from purified MeGAXn. Overall, the
      present study demonstrates that direct alkaline treatment of sweet sorghum
      bagasse is useful to improve the bioavailability of MeGAXn for MR44-mediated
      conversion to U-XOS with average degrees of polymerization of 11-12, providing
      alternative resources with applications in nutrition and human and veterinary
      medicine.

PMID- 29634786
TI  - Environmental Indicator Principium with Case References to Agricultural Soil,
      Water, and Air Quality and Model-Derived Indicators.
AB  - Environmental indicators are powerful tools for tracking environmental changes,
      measuring environmental performance, and informing policymakers. Many diverse
      environmental indicators, including agricultural environmental indicators, are
      currently in use or being developed. This special collection of technical papers
      expands on the peer-reviewed literature on environmental indicators and their
      application to important current issues in the following areas: (i) model-derived
      indicators to indicate phosphorus losses from arable land to surface runoff and
      subsurface drainage, (ii) glutathione-ascorbate cycle-related antioxidants as
      early-warning bioindicators of polybrominated diphenyl ether toxicity in
      mangroves, and (iii) assessing the effectiveness of using organic matrix biobeds
      to limit herbicide dissipation from agricultural fields, thereby controlling on
      farm point-source pollution. This introductory review also provides an overview
      of environmental indicators, mainly for agriculture, with examples related to the
      quality of the agricultural soil-water-air continuum and the application of model
      derived indicators. Current knowledge gaps and future lines of investigation are
      also discussed. It appears that environmental indicators, particularly those for
      agriculture, work efficiently at the field, catchment, and local scales and serve
      as valuable metrics of system functioning and response; however, these indicators
      need to be refined or further developed to comprehensively meet community
      expectations in terms of providing a consistent picture of relevant issues and/or
      allowing comparisons to be made nationally or internationally.

PMID- 29634787
TI  - Removal of Pollutants in Different Landfill Leachate Treatment Processes on the
      Basis of Organic Matter Fractionation.
AB  - A combination of processes was required for the proper treatment of old landfill
      leachate, as it contained a high concentration of pollutants. Humic substances
      comprised half of the total organic carbon in the raw leachate. Mobility of di(2
      ethylhexyl) phthalate (DEHP) and metals could depend on the fate of these
      substances. Characterization of carbon in raw leachate and effluent of the
      membrane bioreactor, biofiltration, electro-oxidation, electro-coagulation, and
      nanofiltration showed complete removal of suspended solids and colloids. Physical
      processes could not remove the hydrophilic fraction due to its lower molecular
      weight. However, high removal of the hydrophilic fraction with a molecular weight
      <500 Da was expected in the biological process. In comparison with fulvic acid,
      larger sized humic acid resulted in complete removal by physicochemical
      processes. Because of DEHP partitioning on dissolved organic matter, especially
      on humic substances, its removal could be correlated with total organic carbon
      removal. Metals such as iron, aluminum, magnesium, and lead showed removal
      efficiency >80% in biological processes. Electro-deposition on the surface of an
      electrode and precipitation by hydroxide resulted in removal efficiencies >90 and
      >50% in electro-coagulation and electro-oxidation, respectively. Rejection of
      metals by nanofiltration was >80% and depended on the size and charge of cation.
      All in all, a combination of membrane bioreactor and nanofiltration seems to be
      the optimal process configuration for efficient treatment of old landfill
      leachate.

PMID- 29634788
TI  - Portable Automation of Static Chamber Sample Collection for Quantifying Soil Gas
      Flux.
AB  - Quantification of soil gas flux using the static chamber method is labor
      intensive. The number of chambers that can be sampled is limited by the spacing
      between chambers and the availability of trained research technicians. An
      automated system for collecting gas samples from chambers in the field would
      eliminate the need for personnel to return to the chamber during a flux
      measurement period and would allow a single technician to sample multiple
      chambers simultaneously. This study describes hamber utomated ampling quipment
      (Flux) to collect and store chamber headspace gas samples at assigned time points
      for the measurement of soil gas flux. The FluxCASE design and operation is
      described, and the accuracy and precision of the FluxCASE system is evaluated. In
      laboratory measurements of nitrous oxide (NO), carbon dioxide (CO), and methane
      (CH) concentrations of a standardized gas mixture, coefficients of variation
      associated with automated and manual sample collection were comparable,
      indicating no loss of precision. In the field, soil gas fluxes measured from
      FluxCASEs were in agreement with manual sampling for both NO and CO. Slopes of
      regression equations were 1.01 for CO and 0.97 for NO. The 95% confidence limits
      of the slopes of the regression lines included the value of one, indicating no
      bias. Additionally, an expense analysis found a cost recovery ranging from 0.6 to
      2.2 yr. Implementing the FluxCASE system is an alternative to improve the
      efficiency of the static chamber method for measuring soil gas flux while
      maintaining the accuracy and precision of manual sampling.

PMID- 29634789
TI  - Filter Membrane Effects on Water-Extractable Phosphorus Concentrations from Soil.
AB  - To accurately assess P concentrations in soil extracts, standard laboratory
      practices for monitoring P concentrations are needed. Water-extractable P is a
      common analytical test to determine P availability for leaching from soils, and
      it is used to determine best management practices. Most P analytical tests
      require filtration through a filter membrane with 0.45-MUm pore size to
      distinguish between particulate and dissolved P species. However, filter membrane
      type is rarely specified in method protocols, and many different types of
      membranes are available. In this study, three common filter membrane materials
      (polyether sulfone, nylon, and nitrocellulose), all with 0.45-MUm pore sizes,
      were tested for analytical differences in total P concentrations and dissolved
      reactive P (DRP) concentrations in water extracts from six soils sampled from two
      regions. Three of the extracts from the six soil samples had different total P
      concentrations for all three membrane types. The other three soil extracts had
      significantly different total P results from at least one filter membrane type.
      Total P concentration differences were as great as 35%. The DRP concentrations in
      the extracts were dependent on filter type in five of the six soil types. Results
      from this research show that filter membrane type is an important parameter that
      affects concentrations of total P and DRP from soil extracts. Thus, membrane type
      should be specified in soil extraction protocols.

PMID- 29634790
TI  - Manganese, Zinc, and pH Affect Cadmium Accumulation in Rice Grain under Field
      Conditions in Southern China.
AB  - Very little has been reported on the effects of pH, Zn, and Mn on Cd uptake in
      rice ( L.) and their levels under field conditions. Rice accumulates a high
      concentration of Cd in acid soils, even at low soil Cd levels. Lime (CaO) was
      spread at 1200 kg ha on the topsoil of a rice field during the tillering stage.
      Effects of liming on rice Cd, soil pH, and amorphous Mn (MnO-AM) were then
      investigated. Slight increases in pH from 5.17 to 5.45 and MnO-AM from 66.3 to
      82.1 mg kg were observed after liming. The proportion of rice samples with a Cd
      concentration greater than the Chinese rice Cd standard (0.2 mg kg dry wt. in
      grain) decreased by ~15%. The pH, which varied from 4.8 to 5.8, did not
      significantly affect rice Cd, whereas soil Cd and Zn had a significantly positive
      effect, together accounting for ~14% of the variance. Soil Mn had significantly
      negative effects on rice Cd, accounting for >18% of the variance. For a Cd
      concentration <0.2 mg kg dry wt. in rice grain, the critical pH value in paddy
      soil was ~5.7, and that for Mn at pH 4.8 to 5.8 was ~300 mg kg. Our findings
      showed that Cd concentration in rice grain in an acid paddy soil increased with
      an increase of Zn and a decrease of Mn when these metals were at sufficient
      levels.

PMID- 29634791
TI  - The Contrasting Effects of Alum-Treated Chicken Manures and KH2PO4 on Phosphorus
      Behavior in Soils.
AB  - Alum [KAl(SO)?12HO] is often added to chicken manure to limit P solubility after
      land application. This is generally ascribed to the formation of Al-PO complexes.
      However, Al-PO complex formation could be affected by the matrix of chicken
      manure, which varies with animal diet. Alum was added to KHPO (as a reference
      material) and two manures from typical chicken farms in China, one from an
      intensive farm (CMIF) and another from free-ranging chickens (CMFR). These were
      subsequently incubated with soils for 100 d to investigate P transformations.
      Alum reduced water-soluble colorimetrically reactive phosphorus (RP) from soils
      amended with manure more effectively than in soils amended with KHPO. Alum
      addition lowered Mehlich-3 RP in soils with CMFR but had no influence on Mehlich
      3 RP in CMIF- or KHPO-amended soils. A comparison of P in digested Mehlich-3
      extracts with RP in undigested samples showed significantly increased P in
      digests of alum-treated CMFR only. Fractionation data indicated that alum
      treatment increased P in the NHF-RP (Al-P) fraction only in soils with KHPO, but
      not in soils with manure treatments. Furthermore, NaOH-extracted nonreactive P
      was markedly higher in soil with alum-treated CMFR relative to normal CMFR. The
      CMFR manure was assumed to contain higher concentrations of organic P because
      these chickens were fed grains only. These results suggest that the formation of
      alum-organic P complexes may reduce P solubility. By comparing alum-treated KHPO
      and manures, it appears that organic matter in manure could interfere with the
      formation of Al-PO complexes.

PMID- 29634792
TI  - Reducing Arsenic Concentration in Panax notoginseng via Contaminant
      Immobilization in Soil Using Fe-Ce Oxide.
AB  - (Burk.) F.H. Chen, a valuable Chinese medicine, is currently confronted with
      arsenic (As) contamination in China due to soil pollution. Our previous research
      demonstrated that Fe(0) and zeolite had a certain inhibitory effect on As
      accumulation in . In order to further reduce As accumulation in the plant, a
      synthetic iron material (Fe-Ce oxide [FC]) with high As adsorption capacity was
      tested for As remediation. In the study, after FC was applied to the As
      contaminated soil, was planted in the soil. The As leaching behavior of the
      treated soil and As accumulation in were evaluated. The results showed that FC
      immobilized As more effectively than Fe(0) and zeolite in soils with high As
      concentrations. When the FC dosage was 0.5 % (w/w), As concentration of root (the
      main medicinal part) decreased by 56%, and root biomass increased by 55%. Results
      indicated FC could reduce the non-specifically adsorbed As fraction (F1) and
      specifically adsorbed As fraction (F2) by 22 to 31% and 5 to 17%, respectively,
      thus reducing the toxicity characteristic leaching procedure leachable As
      concentration by 41 to 67%. The finding of an iron plaque coating on the plant
      root and its function as a barrier to As uptake by is reported here for the first
      time. The occurrence of iron plaque led to a reduction in As concentration in the
      phellem and xylem-phloem by 66 to 80% and 43 to 70%, respectively. Our findings
      will help in developing As contamination control in areas where is planted and
      set a foundation for a FC-based As immobilization technology.

PMID- 29634793
TI  - Nutrient Removal during Stormwater Aquifer Storage and Recovery in an Anoxic
      Carbonate Aquifer.
AB  - Stormwater harvesting coupled to managed aquifer recharge (MAR) provides a means
      to use the often wasted stormwater resource while also providing protection of
      the natural and built environment. Aquifers can act as a treatment barrier within
      a multiple-barrier approach to harvest and use urban stormwater. However, it
      remains challenging to assess the treatment performance of a MAR scheme due to
      the heterogeneity of aquifers and MAR operations, which in turn influences water
      treatment processes. This study uses a probabilistic method to evaluate aquifer
      treatment performance based on the removal of total organic C (TOC), N, and P
      during MAR with urban stormwater in an anoxic carbonate aquifer. Total organic C,
      N, and P are represented as stochastic variables and described by probability
      density functions (PDFs) for the "injectant" and "recovery"; these injectant and
      recovery PDFs are used to derive a theoretical MAR removal efficiency PDF. Four
      long-term MAR sites targeting one of two tertiary carbonate aquifers (T1 and T2)
      were used to describe the nutrient removal efficiencies. Removal of TOC and total
      N (TN) was dominated by redox processes, with median removal of TOC between 50
      and 60% at all sites and TN from 40 to 50% at three sites with no change at the
      fourth. Total P removal due to filtration and sorption accounted for median
      removal of 29 to 53%. Thus, the statistical method was able to characterize the
      capacity of the anoxic carbonate aquifer treatment barrier for nutrient removal,
      which highlights that aquifers can be an effective long-term natural treatment
      option for management of water quality, as well as storage of urban stormwater.

PMID- 29634794
TI  - Sorption of Nitro Explosives to Polymer/Biomass-Derived Biochar.
AB  - Factors affecting the sorptive removal of nitro explosives (2,4,6-trinitrotoluene
      [TNT] and hexahydro-1,3,5-trinitro-1,3,5-triazine [RDX]) to polymer/biomass
      derived biochar were investigated through batch experiments. Compared with that
      of rice ( L.) straw (RS)-derived biochar, the sorption of TNT and RDX to
      polymer/RS-derived biochar was greatly enhanced by >2.5 and 4 times,
      respectively. The type and amount of polymer did not significantly affect the
      sorption of nitro explosives to polymer/RS-derived biochar. Pyrolysis temperature
      did not affect the sorption capacity. Surface treatment with acid or an oxidant
      did not significantly change the sorption capacity, suggesting that polymer
      residues may be strongly responsible for the enhancement. Possible polymer
      residues were identified via gas chromatography mass spectrometry analysis. The
      toxicity characteristic leaching procedure and Microtox bioassay analyses
      indicated that polymer/RS-derived biochar did not show possible harmful effects.
      Our results suggest that polymer/RS-derived biochar can be effectively used as a
      sorbent to remove nitro explosives both in the natural environment and engineered
      systems.

PMID- 29634796
TI  - Glutathione-Ascorbate Cycle Is an Early Warning Indicator of Toxicity of BDE-47
      in Mangroves.
AB  - Mangroves are often exposed to contamination by polybrominated diphenyl ethers
      (PBDEs) from wastewater discharges and solid waste dumping. As one of the most
      prevalent and toxic PBDE congeners in the environment, 2,2',4,4'
      tetrabromodiphenyl ether (BDE-47) and its oxidative stress deserves more
      attention. In plants, the glutathione-ascorbate (GSH-AsA) cycle plays an
      important role in the defensive processes against oxidative stress. However, the
      importance of this cycle in mangroves to defend against PBDE toxicity has not
      been reported. We conducted a study to evaluate the effects of BDE-47 on GSH-AsA
      cycle-related antioxidants in a mangrove species, namely Sheue, H.Y. Liu & J.
      Yong. An 8-wk hydroponic culture experiment was conducted with 1-yr-old seedlings
      of exposed to five levels of BDE-47 contamination. At the two high BDE-47 levels
      (5 and 10 mg L), seedling growth, expressed as dry biomass of leaves and roots,
      was suppressed from Weeks 4 to 8. Parameters in the GSH-AsA cycle in roots and
      leaves changed significantly within the first week after exposure, indicating
      that they were more sensitive indicators to BDE-47 toxicity than growth. The
      suppression of seedling growth, expressed as final biomass production, at the end
      of the 8-wk experiment was positively correlated to the antioxidative responses
      in the first week, confirming the indicative roles of these antioxidants. This is
      the first study to demonstrate that GSH-AsA cycle-related antioxidants in
      mangrove plants are sensitive indicators of BDE-47 toxicity. These antioxidants,
      in particular, ascorbate and glutathione peroxidase, could provide early warning
      of the toxicity of PBDEs.

PMID- 29634797
TI  - Solid Cattle Manure Less Prone to Phosphorus Loss in Tile Drainage Water.
AB  - Forms (e.g., liquid and solid) of manure influence the risk of P loss after land
      application. The objective of this study was to investigate the effects of P
      based application of various forms of cattle manure (liquid, LCM; or solid, SCM)
      or inorganic P as triple superphosphate (IP) on soil P losses in tile drainage
      water. A 4-yr field experiment was conducted in a clay loam soil with a corn (
      L.)-soybean [ (L.) Merr.] rotation in the Lake Erie basin. Over the 4 yr, the
      dissolved reactive P (DRP) flow-weighted mean concentration (FWMC) in tile
      drainage water was greater under SCM fertilization than under either IP or LCM
      fertilization. Despite its lower value on an annual basis, DRP FWMC rose
      dramatically immediately after LCM application. However, the differences in DRP
      FWMC did not result in detectable differences in DRP loads. Regarding particulate
      P and total P losses during the 4 yr, they were 68 and 47%, respectively, lower
      in the soils amended with SCM than in those with IP, whereas both values were
      similar between IP and LCM treatments. Overall, the P contained in solid cattle
      manure was less prone to P loss after land application. Accordingly, the present
      results can provide a basis for manure storage and application of best management
      practices designed to reduce P losses and improve crop growth.

PMID- 29634798
TI  - Influence of Vegetation on Long-term Phosphorus Sequestration in Subtropical
      Treatment Wetlands.
AB  - Sustainable operation of a treatment wetland depends on its continued treatment
      of influent water to achieve desired outflow water quality targets. Water
      treatment or nutrient reduction is attained by a combination of biotic and
      abiotic processes. We studied one of the world's largest treatment wetlands
      established to revive the Florida Everglades from impacts of excessive phosphorus
      (P) inputs. Phosphorus retained in the treatment wetlands is sequestered within
      the accumulated material via biotic and abiotic pathways that are influenced by
      the existing wetland vegetation. Recently accreted soils (RAS) provide a major
      sink for stored P, and long-term P removal efficiency of treatment wetlands is
      governed by the stability of accreted P because more stable P pools are less
      susceptible to mobilization and loss. We quantified reactive P (extracted with
      acid and alkali) and nonreactive P (not extracted with acid and alkali) pools in
      wetland soils by using an operationally defined P fractionation scheme and
      assessed the effect of emergent vs. submerged vegetation communities on stability
      of sequestered P. Reactive P comprised 63 to 79% of total P in wetland soils
      without a clear difference between two vegetation groups. The quantities of
      reactive P forms (inorganic vs. organic P) were significantly different between
      two vegetation types. A higher proportion of reactive P was stored as organic P
      in flocculent detrital organic matter (floc) and RAS under emergent vegetation
      (46-47% total P) in comparison with submerged vegetation (21-34% total P). The
      dominant P removal pathway in the submerged vegetation system was associated with
      calcium whereas plant uptake and peat burial appeared to be the main pathway in
      the emergent vegetation system.

PMID- 29634799
TI  - Metals in Soil and Runoff from a Piedmont Hay Field Amended with Broiler Litter
      and Flue Gas Desulfurization Gypsum.
AB  - Flue gas desulfurization gypsum (FGDG) from coal-fired power plants is readily
      available for agricultural use in many US regions. Broiler litter (BL) provides
      plant available N, P, and K but can be a source of unwanted As, Cu, and Zn. As a
      source of Ca and S, FGDG can reduce losses of P and other elements in runoff from
      BL-amended areas. Rainfall simulation plots (2.0 m) were established on a
      Piedmont Cecil soil growing 'Coastal' bermudagrass ( L.) for hay. Accumulation
      and transport of As, Cu, Cd, Cr, Hg, Pb, and Zn were evaluated after annual BL
      applications (13.5 Mg ha) with four FGDG rates (0, 2.2, 4.5, 9.0 Mg ha) and two
      FGDG treatments (0 and 9 Mg ha) without BL. Runoff As concentrations were sixfold
      greater with BL than without ( <= 0.01) and were similar to BL with FGDG at 2.2,
      4.5 or 9.0 Mg ha ( <= 0.10). Runoff concentrations of target elements did not
      increase where FGDG was applied alone. After three annual applications of FGDG
      and BL, soil concentrations of As, Cr, Pb, Hg, and Cu were well below levels of
      environmental concern. Our findings indicate that runoff losses of As from BL
      application are not reduced with FGDG but support other research indicating no
      identifiable environmental risks from FGDG beneficial use in agricultural
      systems.

PMID- 29634800
TI  - Limited Dissolved Phosphorus Runoff Losses from Layered Double Hydroxide and
      Struvite Fertilizers in a Rainfall Simulation Study.
AB  - The enrichment of P in surface waters has been linked to P runoff from
      agricultural fields amended with fertilizers. Novel slow-release mineral
      fertilizers, such as struvite and P-exchanged layered double hydroxides (LDHs),
      have received increasing attention for P recycling from waste streams, and these
      fertilizers may potentially reduce the risk of runoff losses. Here, a rainfall
      simulation experiment was performed to evaluate P runoff associated with the
      application of recycled slow-release fertilizers relative to that of a soluble
      fertilizer. Monoammonium phosphate (MAP), struvite, and LDH granular fertilizers
      were broadcasted at equal total P doses on soil packed in trays (5% slope) and
      covered with perennial ryegrass ( L.). Four rainfall simulation events of 30 min
      were performed at 1, 5, 15, and 30 d after the fertilizer application. Runoff
      water from the trays was collected, filtered, and analyzed for dissolved P. For
      the MAP treatment, P runoff losses were high in the first two rain events and
      leveled off in later rain events. In total, 42% of the applied P in the MAP
      treatment was lost due to runoff. In the slow-release fertilizer treatments, P
      runoff losses were limited to 1.9 (struvite) and 2.4% (LDH) of the applied doses
      and were more similar over the different rain events. The use of these novel P
      fertilizer forms could be beneficial in areas with a high risk of surface water
      eutrophication and a history of intensive fertilization.

PMID- 29634801
TI  - Effects of Land-Applied Ammonia Scrubber Solutions on Yield, Nitrogen Uptake,
      Soil Test Phosphorus, and Phosphorus Runoff.
AB  - Ammonia (NH) scrubbers reduce amounts of NH and dust released from animal rearing
      facilities while generating nitrogen (N)-rich solutions, which may be used as
      fertilizers. The objective of this study was to determine the effects of various
      NH scrubber solutions on forage yields, N uptake, soil-test phosphorus (P), and P
      runoff. A small plot study was conducted using six treatments: (i) an
      unfertilized control, (ii) potassium bisulfate (KHSO) scrubber solution, (iii)
      aluminum sulfate [Al(SO) ?14HO, alum] scrubber solution, (iv) sodium bisulfate
      (NaHSO) scrubber solution, (v) sulfuric acid (HSO) scrubber solution, and (vi)
      ammonium nitrate (NHNO) fertilizer. The scrubber solutions were obtained from ARS
      Air Scrubbers attached to commercial broiler houses. All N sources were applied
      at a rate of 112 kg N ha. Plots were harvested approximately every 4 wk and soil
      test P measurements were made, then a rainfall simulation study was conducted.
      Cumulative forage yields were greater ( < 0.05) for KHSO (7.6 Mg ha) and NaHSO
      (7.5 Mg ha) scrubber solutions than for alum (6.7 Mg ha) or HSO (6.5 Mg ha)
      scrubber solutions or for NHNO (6.9 Mg ha). All N sources resulted in higher
      yields than the control (5.1 Mg ha). The additional potassium in the KHSO
      treatment likely resulted in higher yields. Although Mehlich-III-extractable P
      was not affected, water-extractable P in soil was lowered by the alum-based
      scrubber solution, which also resulted in lower P runoff. This study demonstrates
      that N captured using NH scrubbers is a viable N fertilizer.

PMID- 29634802
TI  - Fate of Manure-Borne Pathogens during Anaerobic Digestion and Solids Separation.
AB  - Anaerobic digestion can inactivate zoonotic pathogens present in cattle manure,
      which reduces transmission of these pathogens from farms to humans through the
      environment. However, the variability of inactivation across farms and over time
      is unknown because most studies have examined pathogen inactivation under ideal
      laboratory conditions or have focused on only one or two full-scale digesters at
      a time. In contrast, we sampled seven full-scale digesters treating cattle manure
      in Wisconsin for 9 mo on a biweekly basis ( = 118 pairs of influent and effluent
      samples) and used real-time quantitative polymerase chain reaction to analyze
      these samples for 19 different microbial genetic markers. Overall, inactivation
      of pathogens and fecal indicators was highly variable. When aggregated across
      digester and season, log-removal values for several representative microorganisms
      bovine , -like CowM3, and bovine polyomavirus-were 0.78 +/- 0.34, 0.70 +/- 0.50,
      and 0.53 +/- 0.58, respectively (mean +/- SD). These log-removal values were up
      to two times lower than expected based on the scientific literature. Thus, our
      study indicates that full-scale anaerobic digestion of cattle manure requires
      optimization with regard to pathogen inactivation. Future studies should focus on
      identifying the potential causes of this suboptimal performance (e.g.,
      overloading, poor mixing, poor temperature control). Our study also examined the
      fate of pathogens during manure separation and found that the majority of
      microbes we detected ended up in the liquid fraction of separated manure. This
      finding has important implications for the transmission of zoonotic pathogens
      through the environment to humans.

PMID- 29634804
TI  - ACS324.1 JOURNAL OF ENVIRONMENTAL QUALITY EDITORIAL BOARD 2017 Annual Reports.

PMID- 29634803
TI  - Impact of Nitrogen Application Rate on Switchgrass Yield, Production Costs, and
      Nitrous Oxide Emissions.
AB  - Switchgrass ( L.) has been promoted as a potential feedstock for cellulosic
      biofuel in the United States. Switchgrass is known to respond to N fertilizer,
      but optimal rates remain unclear. Given the potential nonlinear response of
      nitrous oxide (NO) emissions to N inputs, N additions to switchgrass above
      optimal levels could have large impacts on the greenhouse gas balance of
      switchgrass-based biofuel. Additionally, N additions are likely to have large
      impacts on switchgrass production costs. Yield, N removal, and net returns were
      measured in switchgrass receiving 0 to 200 kg N ha in Manhattan, KS, from 2012 to
      2014. Emissions of NO were measured in the 0- to 150-kg N ha treatments. Total
      emissions of NO increased from 0.2 to 3.0 kg NO-N ha as N inputs increased from 0
      to 150 kg N ha. The 3-yr averages of fertilizer-induced emission factors were
      0.7, 2.1, and 2.6% at 50, 100, and 150 kg N ha, respectively. Removal of N at
      harvest increased linearly with increasing N rate. Switchgrass yields increased
      with N inputs up to 100 to 150 kg N ha, but the critical N level for maximum
      yields decreased each year, suggesting that N was being applied in excess at
      higher N rates. Net returns were maximized at 100 kg N ha at both a high and low
      urea cost (US$394.71 and $945.91 ha, respectively). These results demonstrate
      that N inputs were necessary to increase switchgrass productivity, but rates
      exceeding optimal levels resulted in excessive NO emissions and increased costs
      for producers.

PMID- 29634805
TI  - Modeling Phosphorus Losses through Surface Runoff and Subsurface Drainage Using
      ICECREAM.
AB  - Modeling soil phosphorus (P) losses by surface and subsurface flow pathways is
      essential in developing successful strategies for P pollution control. We used
      the ICECREAM model to simultaneously simulate P losses in surface and subsurface
      flow, as well as to assess effectiveness of field practices in reducing P losses.
      Monitoring data from a mineral-P-fertilized clay loam field in southwestern
      Ontario, Canada, were used for calibration and validation. After careful
      adjustment of model parameters, ICECREAM was shown to satisfactorily simulate all
      major processes of surface and subsurface P losses. When the calibrated model was
      used to assess tillage and fertilizer management scenarios, results point to a
      10% reduction in total P losses by shifting autumn tillage to spring, and a 25.4%
      reduction in total P losses by injecting fertilizer rather than broadcasting.
      Although the ICECREAM model was effective in simulating surface and subsurface P
      losses when thoroughly calibrated, further testing is needed to confirm these
      results with manure P application. As illustrated here, successful use of
      simulation models requires careful verification of model routines and
      comprehensive calibration to ensure that site-specific processes are accurately
      represented.

PMID- 29634806
TI  - Chemical Characterization and Source Apportionment of PM2.5 in a Nonattainment
      Rocky Mountain Valley.
AB  - Severe air pollution has significant adverse health effects and poses a threat to
      public health in many communities, including nonattainment areas in the Unites
      States. To develop effective control strategies to reduce air pollution with
      minimum economic cost, one of the biggest challenges is to quantify the
      contributions from different sources. By combining chemical analyses, Positive
      Matrix Factorization modeling, and emission inventory development, this study
      identified primary and secondary sources of particulate matter with a diameter of
      <2.5 MUm (PM) in a nonattainment Rocky Mountain valley (i.e., West Silver Valley
      [WSV]) in Idaho. The results show that biomass burning is the dominant source and
      contributes ~84% of the PM concentration in the valley. The study also identified
      influences on the WSV PM concentrations from traffic (7.4%), soil dust (3.4%),
      and secondary aerosols (4.8%). The results of this paper represent the first
      report on the chemical composition and source apportionment of PM in mountain
      valleys of northern Idaho and have been used to develop effective strategies to
      reduce the PM concentrations in the WSV. Moreover, this study provides detailed
      equations and methods in PM speciation, accounting for artifacts of the chemical
      analysis, Positive Matrix Factorization modeling, and emission inventory
      development, which can be used for source apportionment of severe air pollution
      in other regions.

PMID- 29634807
TI  - Mechanisms of Loss of Agricultural Odorous Compounds in Sample Bags of Nalophan,
      Tedlar, and PTFE.
AB  - Alteration of the chemical composition of odor samples during storage in polymer
      sample bags can significantly impair the accuracy of subsequent odor evaluations.
      To overcome or minimize this effect, the mechanisms determining compound loss
      must be more thoroughly understood. The present study examines the storage
      stability of a selection of key odorants from livestock production in polymer
      sample bags of Nalophan, Tedlar, and polytetrafluoroethylene (PTFE). The
      compounds included are acetic acid, butanoic acid, propanoic acid, 3
      methylbutanoic acid, hydrogen sulfide, methanethiol, dimethyl sulfide,
      trimethylamine, and 4-methylphenol. The fate of the unrecovered compound
      fractions is clarified by means of thermal desorption and concentric double bags,
      allowing estimation of the magnitude of losses due to adsorption and diffusion,
      respectively. The degree of recovery was found to be PTFE > Tedlar > Nalophan,
      and smaller ratios of bag surface area to sample volume improved the recovery
      significantly. Furthermore, PTFE bags were found far superior for maintaining the
      original sample humidity and for storing 4-methylphenol. Analysis of sample
      humidity, partitioning coefficients, and thermal desorption suggested that the
      loss in PTFE bags was mainly controlled by adsorption, whereas for Nalophan and
      Tedlar, compound loss is a combined effect of adsorption and diffusion. It is
      suggested to heat the bags when evacuating the sample for analysis, as this was
      found to improve the recovery significantly. For a 5-L PTFE bag, all odorants
      could be found at concentration levels between 71.6 and 98.8% even after 48 h of
      storage when heated to 57 degrees C prior to analysis.

PMID- 29634808
TI  - Mineral Fertilizer and Manure Effects on Leached Inorganic Nitrogen, Nitrate
      Isotopic Composition, Phosphorus, and Dissolved Organic Carbon under Furrow
      Irrigation.
AB  - A better understanding of nutrient leaching in furrow irrigated agriculture is
      needed to optimize fertilizer use and avoid contamination of water supplies. In
      this field study (2003-2006), we measured deep percolation fluxes at 1.2-m depth
      and associated nutrient concentrations and mass losses from dairy manure nitrogen
      (N) or mineral N (urea, sodium nitrate [NaNO])-amended soils (372 kg available N
      ha in 4 yr) and nonamended controls and determined the deltaN-NO and deltaO-NO
      isotope ratios in the leached nitrate. Flow-weighted concentration means for
      individual irrigations varied widely, from near zero to as much as 250 mg L for
      NO-N, 480 MUg L for dissolved reactive phosphorus (DRP), 43 mg L for dissolved
      organic C (DOC), and 390 mg L for chloride (Cl). Relative to other treatments,
      mineral fertilizer increased NO-N concentrations 2.6- to 3-fold and Cl
      concentrations 2.6- to 3.6-fold in deep leachate, particularly when NaNO was
      applied in 2004 and 2006, and produced maximum mean season-long NO-N and Cl
      losses. Manure and control treatments produced similar leachate nutrient mass
      losses, and for some irrigation periods, mineral fertilizer produced 85 and 97%
      lesser DRP losses and two times greater Cl losses compared with manure and
      control treatments. Four-year cumulative losses among treatments differed only
      for Cl. Isotopic composition of deep-leached nitrate indicates that both
      transformation and biologic cycling of mineral and manure N are rapid in these
      soils, which, with percolation volume, influence the amounts of NO-N and DOC
      leached. In light of the potential negative effects associated with either
      fertilizer type, and because even nonamended soils produced substantial amounts
      of leached NO-N (69.5 kg ha yr), management must minimize percolation water
      losses to limit nutrient losses from these fertilized, furrow-irrigated soils.

PMID- 29634809
TI  - Chloromethane Degradation in Soils: A Combined Microbial and Two-Dimensional
      Stable Isotope Approach.
AB  - Chloromethane (CHCl, methyl chloride) is the most abundant volatile halocarbon in
      the atmosphere and involved in stratospheric ozone depletion. The global CHCl
      budget, and especially the CHCl sink from microbial degradation in soil, still
      involves large uncertainties. These may potentially be resolved by a combination
      of stable isotope analysis and bacterial diversity studies. We determined the
      stable isotope fractionation of CHCl hydrogen and carbon and investigated
      bacterial diversity during CHCl degradation in three soils with different
      properties (forest, grassland, and agricultural soils) and at different
      temperatures and headspace mixing ratios of CHCl. The extent of chloromethane
      degradation decreased in the order forest > grassland > agricultural soil. Rates
      ranged from 0.7 to 2.5 MUg g dry wt. d for forest soil, from 0.1 to 0.9 MUg g dry
      wt. d for grassland soil, and from 0.1 to 0.4 MUg g dry wt. d for agricultural
      soil and increased with increasing temperature and CHCl supplementation. The
      measured mean stable hydrogen enrichment factor of CHCl of -50 +/- 130/00 was
      unaffected by temperature, mixing ratio, or soil type. In contrast, the stable
      carbon enrichment factor depended on CHCl degradation rates and ranged from -38
      to -110/00. Bacterial community composition correlated with soil properties was
      independent from CHCl degradation or isotope enrichment. Nevertheless, increased
      abundance after CHCl incubation was observed in 21 bacterial operational
      taxonomical units (OTUs at the 97% 16S RNA sequence identity level). This
      suggests that some of these bacterial taxa, although not previously associated
      with CHCl degradation, may play a role in the microbial CHCl sink in soil.

PMID- 29634810
TI  - Enhanced Dissipation of Selected Herbicides in a Simulated Organic Matrix Biobed:
      A System to Control On-Farm Point-Source Pollution.
AB  - Most farms have a centralized location to fill spray tanks with pesticides and to
      flush and clean application equipment. These sites, depending on the frequency of
      use, could be significant sources of surface and groundwater contamination. One
      approach to minimize this contamination is to install a treatment system, such as
      a biobed. This study sought to construct a biobed and test the effects of
      different biomix materials in enhancing the dissipation of herbicides widely used
      in crop production. The four types of biomix evaluated had mixing ratios by
      volume of (1) 12.5% straw:62.5% soil:25% peat, (2) 25% straw:50% soil:25% peat,
      (3) 12.5% straw:62.5% soil:25% compost, and (4) 25% straw:50% soil:25% compost.
      The dissipation rates of acetochlor, atrazine, pendimethalin, and trifluralin at
      different incubation times over 90 d were evaluated. The dissipation of atrazine
      and pendimethalin in the biomixes were faster than in soil. The half-lives for
      atrazine were 27.8 d in soil and 14.3 to 20.2 d in the biomixes and those of
      pendimethalin were 25.5 d in soil and 11.9 to 14.8 d in the biomixes. The
      dissipation rates and half-lives of acetochlor were similar to those in soil; the
      trifluralin dissipation rates were slower in the biomixes. The phenol oxidase
      activity was higher in the peat biomixes than in those containing compost. The
      results showed that biobed materials, especially those with peat, are effective
      in degrading selected herbicides.

PMID- 29634811
TI  - Using Heart Pump Data to Manage Cardiogenic Shock.

PMID- 29634812
TI  - Patient-Derived Organoids Predict Cancer Treatment Response.

PMID- 29634813
TI  - Personal Genomics and Cryptocurrency Team Up.

PMID- 29634815
TI  - Incorrect Data Reported.

PMID- 29634814
TI  - A 58-Year-Old Man With a Macerated Rash of the Neck and Axilla.

PMID- 29634816
TI  - Toward a United States of Health: Implications of Understanding the US Burden of
      Disease.

PMID- 29634818
TI  - Sequencing of Tumor DNA to Guide Cancer Risk Assessment and Therapy.

PMID- 29634819
TI  - Queries and Minor Notes.

PMID- 29634820
TI  - Queries and Minor Notes.

PMID- 29634821
TI  - Acute Malnutrition and Anemia Among Rohingya Children in Kutupalong Camp,
      Bangladesh.

PMID- 29634822
TI  - Fracking and Climate Change.

PMID- 29634823
TI  - Diagnosing Acute Mountain Sickness.

PMID- 29634824
TI  - Treatment Approaches for Malignant Pleural Effusion.

PMID- 29634825
TI  - Fracking and Climate Change-Reply.

PMID- 29634826
TI  - Diagnosing Acute Mountain Sickness-Reply.

PMID- 29634827
TI  - Treatment Approaches for Malignant Pleural Effusion.

PMID- 29634828
TI  - Benralizumab (Fasenra) for Severe Eosinophilic Asthma.

PMID- 29634830
TI  - Medications for Asthma.

PMID- 29634832
TI  - A Third Option.

PMID- 29634834
TI  - Lasting Effects of Childhood TBI.

PMID- 29634835
TI  - Risks of "Raw Water".

PMID- 29634836
TI  - Simulation of the Effect of Different Presbyopia-Correcting Intraocular Lenses
      With Eyes With Previous Laser Refractive Surgery.
AB  - PURPOSE: To simulate the optical performance of three presbyopia-correcting
      intraocular lenses (IOLs) implanted in eyes with previous laser refractive
      surgery. METHODS: A simulation of the through-focus modulation transfer function
      (MTF) was performed for three presbyopia-correcting IOLs (Mplus, Oculentis GmbH,
      Berlin, Germany; Symfony, Johnson & Johnson Vision, Santa Ana, CA; and Mini Well,
      SIFI S.p.A., Lavinaio, Italy) in one eye with previous myopic LASIK and another
      with hyperopic LASIK. Real topographic data and the wavefront aberration profile
      of each IOL obtained with a Hartmann-Shack sensor were used. RESULTS: In the eye
      with myopic LASIK, all IOLs lost optical quality at near and intermediate
      distances for 4- and 4.7-mm pupil size. For 3-mm pupil size, the Mini Well IOL
      showed the best intermediate and near MTF and maintained the far focus
      independently of the pupil. In the eye with hyperopic LASIK, the Mini Well IOL
      showed an intermediate, distance, and -4.00-diopter (D) foci for all pupils. The
      Symfony IOL showed a depth of focus at far and intermediate distance for 3-mm and
      a focus at -2.50 D in the rest. The Mplus showed a focus of -4.50 and -3.00 D for
      the 3- and 4-mm pupil, respectively. CONCLUSIONS: The Mini Well and Symfony IOLs
      seem to work better than the Mplus IOL in eyes with previous myopic LASIK. With
      previous hyperopic LASIK, the Mini Well IOL seems to be able to provide
      acceptable near, intermediate, and far foci for all pupil sizes. These findings
      should be confirmed in future clinical studies. [J Refract Surg. 2018;34(4):222
      227.].

PMID- 29634837
TI  - Visual Performance of a New Extended Depth-of-Focus Intraocular Lens Compared to
      a Distance-Dominant Diffractive Multifocal Intraocular Lens.
AB  - PURPOSE: To investigate the clinical performance of a new extended depth-of-focus
      (EDOF) intraocular lens (IOL) and compare it to that of a distance-dominant
      diffractive multifocal IOL. METHODS: Patients implanted with an EDOF IOL (Mini
      Well; SIFI, Catania, Italy) inducing spherical aberration and with a multifocal
      IOL (ReSTOR SV25T; Alcon Laboratories, Inc., Fort Worth, TX) were analyzed. The
      following monocular parameters were investigated: corrected distance visual
      acuity (CDVA), distance-corrected near visual acuity (DCNVA), reading speed,
      defocus curve, contrast sensitivity, and halos and glare as quantified by a
      simulator (Halo & Glare Simulator; Eyeland-Design Network GmbH, Vreden, Germany)
      and questionnaire. RESULTS: Twenty patients with the EDOF IOL and 37 with the
      multifocal IOL were enrolled. No statistically significant difference was
      observed for CDVA. The defocus curve of the EDOF IOL revealed no gaps for the
      intermediate range. Statistically significant differences were observed at -1.00
      diopter (D) (EDOF IOL: 0.08 +/- 0.09 logMAR; multifocal IOL: 0.21 +/- 0.12
      logMAR; P < .0001) and -1.50 D defocus (EDOF IOL: 0.15 +/- 0.11 logMAR;
      multifocal IOL: 0.24 +/- 0.13 logMAR; P = .0122). The reading speed at 40 cm was
      similar at all print sizes. The mean DCNVA was the same (EDOF IOL: 0.35 +/- 0.14
      logRAD, multifocal IOL: 0.35 +/- 0.13 logRAD). No differences in contrast
      sensitivity were detected. According to the simulator, halos had a smaller mean
      size (P = .0439) and a lower mean intensity (P = .0222) with the EDOF IOL. No
      statistically significant differences were detected for glare size. CONCLUSIONS:
      The new EDOF IOL performed similarly to a multifocal IOL at distance and near but
      was superior at intermediate distances. [J Refract Surg. 2018;34(4):228-235.].

PMID- 29634838
TI  - Through-Focus Optical Bench Performance of Extended Depth-of-Focus and Bifocal
      Intraocular Lenses Compared to a Monofocal Lens.
AB  - PURPOSE: To analyze the optical performance and the effect of halos on modulation
      transfer function (MTF) of an extended depth-of-focus (EDOF) intraocular lens
      (IOL) compared to low add bifocal, high add bifocal, and monofocal IOLs. METHODS:
      The optical bench system was set up to evaluate the MTF and point spread function
      images for analyzing halos around the focused image with four different IOLs
      (TECNIS ZCB00, ZXR00, ZKB00, and ZMB00; Abbott Medical Optics, Inc., Santa Ana,
      CA). They were measured within a defocus range from +0.50 to -4.00 diopters (D).
      RESULTS: The EDOF IOL showed good and stable image quality from far to
      intermediate distance. The near visual performance was limited with the EDOF IOL
      compared to low add and high add power bifocal IOLs. Monofocal and EDOF IOLs
      focused light more tightly at far distance and showed higher intensity at the
      core compared to low and high add bifocal IOLs. The peak core intensity and the
      relative halo intensity of the EDOF IOL were comparable to those obtained from
      the monofocal IOL. A negative significant correlation was found in all IOLs
      between the relative halo intensity and MTF within a defocus diopter range from
      0.00 to -3.00 D (P < .05). CONCLUSIONS: The EDOF IOL had distance acuity optical
      quality and halo effect similar to monofocal IOLs but worse near acuity compared
      to conventional bifocal IOLs. [J Refract Surg. 2018;34(4):236-243.].

PMID- 29634839
TI  - Biological Lenticule Implantation for Correction of Hyperopia: An Ex Vivo Study
      in Human Corneas.
AB  - PURPOSE: To evaluate changes in corneal tomography after stromal lenticule
      implantation ex vivo, with respect to the dependency of the lenticule thickness
      and implantation depth on the corneal curvature and the postoperative
      biomechanical strength at increased chamber pressure. METHODS: Twenty-eight human
      donor corneas underwent pocket implantation of refractive stromal lenticules.
      Four groups were created by the combination of two implantation depths (110 and
      160 um) and two lenticule thicknesses (95 um = 4.00 diopters [D], 150 um = 8.00
      D). Sagittal keratometry and total corneal refractive power (TCRP4mm,apex,zone)
      were obtained for the front and back curvature with Pentacam HR (Oculus
      Optikgerate GmbH, Wetzlar, Germany) at chamber pressures of 15 and 40 mm Hg.
      RESULTS: The anterior curvature steepening was comparable between the 4.00 D and
      8.00 D groups (P > .141), but more pronounced with 110 um implantation depth (P <
      .038). The posterior curvature flattened significantly more after implantation of
      8.00 D than 4.00 D lenticules (P < .002), but was similar at 110 and 160 um
      implantation depths (P > .071). Average DeltaTCRP for the 4.00 D and 8.00 D
      groups was 3.10 +/- 0.60 and 5.30 +/- 1.66 diopters (D) at 110-um depth,
      respectively (P = .003), but 1.99 +/- 0.79 and 3.36 +/- 1.45 D at 160-um depth,
      respectively (P = .066). The relative correction achieved was 66% to 78% at 110
      um depth and 42% to 50% at 160-um depth, but similar when using 4.00 D and 8.00 D
      lenticules. Increased chamber pressure caused significant anterior and posterior
      curvature steepening after implantation in all four groups (P < .001), but not
      before implantation (P > .632). CONCLUSIONS: The power of the implanted lenticule
      must be higher than the intended correction, and customized to the chosen
      implantation depth. Biomechanical strength seems to decrease after lenticule
      implantation. [J Refract Surg. 2018;34(4):245-252.].

PMID- 29634840
TI  - Early Tomographic Changes in the Eyes of Patients With Keratoconus.
AB  - PURPOSE: To identify tomographic variables best suited for detecting keratoconus
      before manifestation of ectatic changes and showing disease progression in the
      early stage. METHODS: Twenty-seven patients with diagnosed unilateral keratoconus
      were followed up for their fellow eye, which had not yet shown any ectatic
      changes, to determine initial change indicators toward keratoconus disease.
      Variables were compared to 50 normal eyes without any known disease. A following
      receiver operating characteristic (ROC) analysis was performed to reveal the
      variables best used to discriminate healthy eyes from early ectatic eyes.
      RESULTS: The calculated mean difference of the cylinder for total corneal
      refractive power was only 0.07 +/- 0.32 diopters (D) (anterior astigmatism = 0.12
      +/- 0.28 D and posterior astigmatism = 0.02 +/- 0.10 D). ROC revealed the index
      of height decentration with an area under the curve of 0.788 +/- 0.054 as the
      most suitable to differentiate between eyes of healthy patients and the non
      ectatic eye of patients with asymmetrical keratoconus, followed by the index of
      vertical asymmetry of 0.772 +/- 0.057 and a keratoconus index of 0.743 +/- 0.062.
      However, with progression of the eyes into early ectactic stages, the ROC showed
      the highest area under the curve for D-index (0.876 +/- 0.039), followed by index
      of height decentration (0.855 +/- 0.046) and index of vertical asymmetry (0.842
      +/- 0.046). CONCLUSIONS: Early stages of keratoconus are hard to diagnose and
      best results can be achieved by using index of height decentration and index of
      vertical asymmetry. As the disease progresses, D-index is better suited to
      diagnose an ectasia. Astigmatism, keratometry, and pachymetry barely change in
      the early stages, so these values are not as fitting as corneal elevation
      parameters for early diagnosis. [J Refract Surg. 2018;34(4):254-259.].

PMID- 29634841
TI  - Variation in the Best Fit Sphere Radius of Curvature as a Test to Detect
      Keratoconus Progression on a Scheimpflug-Based Corneal Tomographer.
AB  - PURPOSE: To evaluate the variation in the best fit sphere radius (BFSR) of
      curvature on a Scheimpflug corneal tomographer as a test to detect keratoconus
      progression. METHODS: In this retrospective, comparative, case-control study, two
      groups of eyes with stable or progressive keratoconus were identified based on
      keratometric, refractive, and visual acuity criteria. Two sequential scans were
      used to assess the variation in topometric variables. Receiver operating
      characteristic analysis was conducted for anterior and posterior BFSR values.
      RESULTS: A total of 94 eyes of 62 patients were included in the study; 43 eyes
      were included in the progressive group and 51 eyes in the stable group. In the
      progressive group, these differences were found to be statistically significant
      in sequential scans for the analyzed variables: steepest axis keratometry value
      (K2) = 1.94 +/- 1.70 D (P < .001), maximum keratometry value (Kmax) = 2.62 +/-
      3.08 D (P <= .001), apex pachymetry = 12.233 +/- 13.728 um (P <= .001), anterior
      BFSR = 0.116 +/- 0.107 mm (P <= .001) and posterior BFSR = 0.082 +/- 0.075 mm (P
      <= .001). In the stable group, changes in K2, Kmax, apex pachymetry, anterior
      BFSR, and posterior BFSR were not found to be statistically significant. Analysis
      of the area under the receiver operating characteristic curve (AUROC) showed that
      the best tests for discriminating between progressive and stable groups were the
      variation in the anterior BFSR and variation in K2 (AUROC = 0.940, 95% confidence
      interval [CI] = 0.884 to 0.996 and AUROC = 0.935, 95% CI = 0.881 to 0.990,
      respectively). Variation in the posterior BFSR had an AUROC of 0.863 with a 95%
      CI of 0.775 to 0.950. CONCLUSIONS: Steepening of the BFSR of anterior and
      posterior surface elevation maps could be used as indices for keratoconous
      progression. [J Refract Surg. 2018;34(4):260-263.].

PMID- 29634829
TI  - The State of US Health, 1990-2016: Burden of Diseases, Injuries, and Risk Factors
      Among US States.
AB  - Introduction: Several studies have measured health outcomes in the United States,
      but none have provided a comprehensive assessment of patterns of health by state.
      Objective: To use the results of the Global Burden of Disease Study (GBD) to
      report trends in the burden of diseases, injuries, and risk factors at the state
      level from 1990 to 2016. Design and Setting: A systematic analysis of published
      studies and available data sources estimates the burden of disease by age, sex,
      geography, and year. Main Outcomes and Measures: Prevalence, incidence,
      mortality, life expectancy, healthy life expectancy (HALE), years of life lost
      (YLLs) due to premature mortality, years lived with disability (YLDs), and
      disability-adjusted life-years (DALYs) for 333 causes and 84 risk factors with
      95% uncertainty intervals (UIs) were computed. Results: Between 1990 and 2016,
      overall death rates in the United States declined from 745.2 (95% UI, 740.6 to
      749.8) per 100 000 persons to 578.0 (95% UI, 569.4 to 587.1) per 100 000 persons.
      The probability of death among adults aged 20 to 55 years declined in 31 states
      and Washington, DC from 1990 to 2016. In 2016, Hawaii had the highest life
      expectancy at birth (81.3 years) and Mississippi had the lowest (74.7 years), a
      6.6-year difference. Minnesota had the highest HALE at birth (70.3 years), and
      West Virginia had the lowest (63.8 years), a 6.5-year difference. The leading
      causes of DALYs in the United States for 1990 and 2016 were ischemic heart
      disease and lung cancer, while the third leading cause in 1990 was low back pain,
      and the third leading cause in 2016 was chronic obstructive pulmonary disease.
      Opioid use disorders moved from the 11th leading cause of DALYs in 1990 to the
      7th leading cause in 2016, representing a 74.5% (95% UI, 42.8% to 93.9%) change.
      In 2016, each of the following 6 risks individually accounted for more than 5% of
      risk-attributable DALYs: tobacco consumption, high body mass index (BMI), poor
      diet, alcohol and drug use, high fasting plasma glucose, and high blood pressure.
      Across all US states, the top risk factors in terms of attributable DALYs were
      due to 1 of the 3 following causes: tobacco consumption (32 states), high BMI (10
      states), or alcohol and drug use (8 states). Conclusions and Relevance: There are
      wide differences in the burden of disease at the state level. Specific diseases
      and risk factors, such as drug use disorders, high BMI, poor diet, high fasting
      plasma glucose level, and alcohol use disorders are increasing and warrant
      increased attention. These data can be used to inform national health priorities
      for research, clinical care, and policy.

PMID- 29634842
TI  - The Relationship Between Mechanical Properties, Ultrastructural Changes, and
      Intrafibrillar Bond Formation in Corneal UVA/Riboflavin Cross-linking Treatment
      for Keratoconus.
AB  - PURPOSE: To determine the relationship between mechanical behavior in cross
      linked corneas and changes in the corneal ultrastructure after corneal cross
      linking (CXL). METHODS: Porcine corneas were treated following the "Dresden"
      protocol, the current gold standard for clinical treatment, consisting of
      dropwise application of 0.1% riboflavin in 20% dextran followed by 30 minutes of
      ultraviolet-A (UVA) irradiation. The effect of CXL was assessed using uniaxial
      tensile testing, transmission electron microscopy, and Fourier transform infrared
      spectroscopy, with results compared against corneas treated with each of the
      treatment solution components individually. RESULTS: UVA/riboflavin cross-linked
      corneas displayed 28% +/- 17% increase in the material tangent modulus compared
      with dextran treatment alone, and altered collagen architecture within the first
      300 um of stromal depth consisting of 5% increase in the thickness of collagen
      fibrils, no significant changes to interfibrillar spacing, and an 8% to 12%
      decrease in number of fibrils per unit area. Fourier transform infrared
      spectroscopy confirmed formation of interfibrillar bonds (P = .012) induced by
      UVA-mediated CXL. CONCLUSIONS: The data support a model wherein collagen fibril
      diameter and structural density are fundamental parameters in defining tissue
      stiffening following UVA/riboflavin CXL and provide benchmarks against which
      modifications to the Dresden CXL protocol can be evaluated. [J Refract Surg.
      2018;34(4):264-272.].

PMID- 29634843
TI  - Comparison of the Visual Performance After Implantation of Bifocal and Trifocal
      Intraocular Lenses Having an Identical Platform.
AB  - PURPOSE: To compare the visual performance after bilateral implantation of a
      diffractive bifocal or trifocal intraocular lens (IOL) from the same manufacturer
      using the same IOL platform. METHODS: This prospective, non-randomized,
      controlled study involved patients who had cataract surgery with bilateral
      implantation of bifocal or trifocal IOLs. The near, intermediate, and distance
      visual acuities, defocus curve, optical quality including modulation transfer
      functions and higher-order aberrations, National Eye Institute Visual Functioning
      Questionnaire-14, patient satisfaction, spectacle independence, and perception of
      visual disturbances were assessed in all patients. RESULTS: Fifty eyes (25
      patients) were implanted with a diffractive trifocal IOL (AT LISA tri 839MP; Carl
      Zeiss Meditec, Jena, Germany) and 60 eyes (30 patients) with a diffractive
      bifocal IOL (AT LISA 809M; Carl Zeiss Meditec). The follow-up was 3 months. No
      statistically significant difference was found in distance or near visual acuity
      between the two groups (P >= .05). Uncorrected, corrected, and distance-corrected
      intermediate visual acuities were significantly better in the trifocal IOL group
      (P < .01). In the binocular defocus curve, the visual acuity was also
      significantly better for defocus of -1.00 to -2.00 diopters in eyes with trifocal
      IOL implantation (P < .01). Similar halos and glare were present in the two
      groups. The levels of overall satisfaction were similarly high between groups.
      CONCLUSIONS: Diffractive trifocal IOLs can provide significantly better
      intermediate vision and equivalent distance and near visual performance compared
      to bifocal IOLs and do not induce extra qualitative vision disturbances. [J
      Refract Surg. 2018;34(4):273-280.].

PMID- 29634844
TI  - Two-Year Outcome of a Patient Treated With Phototherapeutic Keratectomy and
      Autologous SMILE Lenticule Transplantation for Flap-Related Complications
      Following LASIK.
AB  - PURPOSE: To describe a patient with flap complications after LASIK who was
      subsequently treated using phototherapeutic keratectomy (PTK) and an autologous
      lenticule transplant obtained via small incision lenticule extraction (SMILE).
      METHODS: A 23-year-old man experienced free flap and partial flap loss in the
      left eye following LASIK, resulting in corneal stroma opacity 1 month later. The
      manifest refraction was -3.25 diopters sphere (DS)/-0.50 diopters cylinder (DC) *
      100 degrees  in the right eye and +2.50 DS/-1.25 DC * 155 degrees  in the left
      eye. His left eye was treated with PTK and transplantation of an autologous
      lenticule obtained from his right eye using the SMILE procedure. RESULTS: At the
      2-year follow-up visit, the uncorrected distance visual acuity of the left eye
      had improved from 20/100 to 20/22 and the corrected distance visual acuity had
      improved from 20/25 to 20/18. Central corneal thickness had increased from 464 to
      499 um. The mean keratometry value had decreased from 45.00 diopters (D) at the 1
      month follow-up visit to 39.40 D at the 2-year follow-up visit. Optical coherence
      tomography examination revealed that the lenticule remained transparent and
      exhibited a visible demarcation line. CONCLUSIONS: The transplantation of an
      autologous lenticule obtained via SMILE combined with PTK improved uncorrected
      and corrected acuity in this patient with flap loss after LASIK. [J Refract Surg.
      2018;34(4):281-285.].

PMID- 29634845
TI  - Posterior Corneal Astigmatism and Efficacy in Refractive Correction.

PMID- 29634846
TI  - Optimal Pocket Depth for Corneal Inlays.

PMID- 29634847
TI  - Feasibility of Using PROMIS(r) in Individuals With Advanced Parkinson's Disease
      and Their Caregivers.
AB  - The purpose of the current study was to test the feasibility of using the Patient
      Reported Outcomes Measurement Information System (PROMIS(r)) measures to assess
      change in self-reported health status for dyads of individuals with advanced
      Parkinson's disease (PD) and their caregivers. Fifteen dyads (N = 30)
      participated and took 11 PROMIS measures. The measures showed good reliability
      (all Cronbach's alphas > 0.82). Dyads reported worse health status than the
      PROMIS reference groups at baseline and 6-month follow up. Paradoxically,
      individuals with PD scored higher in Applied Cognition-General Concerns,
      Companionship, and Emotional Support than the reference groups at both times. The
      only domain that changed significantly for individuals with PD over 6 months was
      Applied Cognition-General Concerns. The results of this study suggest that future
      research (a) could use the PROMIS measures with dyads, and (b) would be warranted
      for tracking changes over time using the PROMIS measures with larger samples,
      garnering more power. In addition, future research could examine if the computer
      adaptive versions work for individuals with advanced PD. [Res Gerontol Nurs.
      2018; 11(3):129-136.].

PMID- 29634848
TI  - Early Readmission Risk Identification for Hospitalized Older Adults With
      Decompensated Heart Failure.
AB  - The current study evaluated risk factors of early hospital readmission in
      geriatric patients with acute heart failure (HF) and analyzed 2,279 consecutively
      hospitalized older adults with decompensated HF from November 2013 to October
      2014 across 15 U.S. hospitals. The eTracker-HF was designed to make risk factors
      known to treating clinicians in electronic health records. Multilevel
      multivariate logistic regression was applied to examine the association between
      risk factors and all-cause and HF 30-day readmission rates. All-cause and HF 30
      day readmission rates were 22.3% and 9.8%, respectively. Old age, non-White
      ethnicity, delirium, physical impairment, ejection fraction <40%, advanced
      chronic kidney disease, and previous myocardial infarction were associated with
      all-cause and HF readmission. Home health care use was inversely associated with
      early readmission. In addition to demographic and cardiovascular risk factors,
      geriatric syndromes were associated with early readmission. Discharge to home
      health care may reduce early readmission in these patients. [Res Gerontol Nurs.
      2018; 11(4):190-197.].

PMID- 29634849
TI  - Recruitment of Individuals With Dementia and Their Carers for Social Research:
      Lessons Learned From Nine Studies.
AB  - Many health and social care research studies report difficulties recruiting
      sufficient numbers of participants, adding to time and money expenditures and
      potentially jeopardizing the generalizability of findings. The current article
      reports the effectiveness and resource requirements of recruitment strategies
      used in nine dementia-related studies conducted in Australia. Articles, notices,
      or advertisements in targeted specialist newsletters were the most cost-effective
      method of recruitment. The use of service providers to aid recruitment yielded
      mixed results, but was lengthy in terms of research time. Online and social media
      were low cost but not reliably effective in terms of recruitment potential.
      Despite using multiple strategies to maximize recruitment, significant challenges
      were encountered achieving the required sample sizes; in most cases these
      challenges resulted in delays in the recruitment phase. Implications for
      researchers in the fields of dementia and general social/health research are
      discussed. [Res Gerontol Nurs. 2018; 11(3):119-128.].

PMID- 29634851
TI  - Response to "IRIS from the Inside".

PMID- 29634853
TI  - Thyroid FNA biopsies comprised of abundant, mature squamous cells can be reported
      as benign: A cytologic study of 18 patients with clinical correlation.
AB  - BACKGROUND: A thyroid nodule comprised almost exclusively of mature, benign
      appearing squamous cells is an uncommon finding in fine-needle aspiration (FNA)
      biopsies of thyroid nodules. Reporting such specimens was not originally
      addressed by The Bethesda System for Reporting Thyroid Cytopathology. The authors
      correlated the biologic behavior of the specimens with their benign cytologic
      appearance through clinical, radiographic, and surgical follow-up. METHODS: The
      pathology archives of 3 tertiary hospitals were searched for thyroid FNA
      specimens consisting of mature squamous cells without atypia. The authors
      reviewed all available slides and included only cases that were moderately to
      highly cellular; nucleated or anucleate squamous cells without atypia comprised
      the vast majority of the cellularity. Available clinical information and/or
      thyroid ultrasound examination(s) were reviewed by an endocrinologist or
      radiologist, respectively. RESULTS: A total of 18 patients (7 men and 11 women;
      age range, 19-76 years) with 20 nodules met the prespecified inclusion criteria.
      The average nodule size was 2.1 cm. Common sonographic characteristics included a
      well-defined appearance, the lack of internal vascularity, a thin outer wall,
      general hypoechogenicity with low-intermediate internal echoes, and posterior
      acoustic enhancement. Clinical and radiographic follow-up (mean, 3.8 years;
      range, <1 to 9 years) was available for 9 patients, and all nodules were stable.
      All 4 cases with histologic follow-up were benign squamous-lined cysts.
      CONCLUSIONS: The findings of the current study suggest that thyroid FNA specimens
      comprised almost exclusively of mature squamous cells can be reported as benign.
      Cancer Cytopathol 2018;126:336-41. (c) 2018 American Cancer Society.

PMID- 29634854
TI  - Restructuring SCAI Committees for Success.

PMID- 29634855
TI  - The under-appreciated and still under-investigated consequences of "supersized"
      access and closure.
AB  - Large bore access and closure of the femoral artery has the potential to cause or
      accelerate local vascular disease The implications of accelerated disease could
      be substantial Further investigation is needed to assess the true short- and long
      term effects.

PMID- 29634856
TI  - TAVR technique tries to go higher than bicuspid valve hurdles.
AB  - Aortic stenosis developed in bicuspid valves is commonly characterized by a
      complex anatomy TAVR may be considered for high risk patients with bicuspid valve
      stenosis but procedure is usually technically challenging High (supra-annular)
      implantation of self-expandable TAVR prostheses may be a valuable option for
      selected patients with bicuspid valve stenosis.

PMID- 29634857
TI  - Looking for the bare necessities.
AB  - The authors suggest that the early durability of the CoreValve implant should not
      be in question based on the results of this modestly sized, but well-done
      postmortem observational study. Given the ever-expanding knowledge of valvular
      degeneration, one thing is clear: more research and study is needed before any
      routine change in clinical practice, such as change it antithrombotic therapy,
      can be recommended. Further autopsy studies of patients who die outside of
      typical healthcare settings and who have had a longer median implant time would
      aid greatly in furthering the understanding of the degeneration and natural
      history of bioprosthetic transcatheter heart valves.

PMID- 29634858
TI  - Too little, too much or just right? Goldilocks revisited....
AB  - This study highlights the low rates of UCA in OHCA patients in a real-world
      setting Presentation with ST elevation, shockable rhythm and history of CAD were
      more likely to result in UCA for OHCA patients Further studies are required to
      help create a systematic and standardized approach to UCA in OHCA patients.

PMID- 29634859
TI  - TAVR in bicuspid aortic valve stenosis: "We are not there yet" to draw final
      conclusions.
AB  - TAVR for bicuspid AS is not associated with excess mortality, but paravalvular
      leak and pacemaker implant is increased compared to tricuspid AS cohorts
      undergoing TAVR. Operators should weigh these potential complications against the
      clinical benefit obtained with TAVR for bicuspid AS patients at high surgical
      risk. A randomized controlled trial comparing TAVR with SAVR in younger, low
      surgical risk patients with-or at least not excluding-bicuspid AS is strongly
      needed.

PMID- 29634860
TI  - The quest for a "diabetic" stent.
AB  - Patients with diabetes mellitus and extensive coronary artery disease generally
      had worse outcomes with early generation drug eluting stents (DES) as compared to
      coronary artery bypass grafting. Initial results with Amphilimus eluting coronary
      stent in patients with diabetes have been promising in small studies The data
      from Sardella et al. should be used, in conjunction with previous clinical
      studies with this DES type, as hypothesis generating for a large multicenter
      randomized trial to aid in our quest to find the "new diabetic stent."

PMID- 29634861
TI  - Early stent thrombosis: Nearly gone, but never forgotten.
AB  - Early stent thrombosis occurs in ~1% of patients treated with primary PCI and
      increases shock, stroke, and mortality. Early stent thrombosis was associated
      with small stent diameter, failure to use glycoprotein inhibitors, and
      bivalirudin use. Minimizing stent thrombosis may require the use of imaging and
      aggressive antithrombotic therapy.

PMID- 29634862
TI  - [The Impact of Medical And Non-Medical Factors on Population Mortality:
      Environment Factors].
AB  - The second analysis was implemented concerning results of study evaluating impact
      of environmental factors on indices of population mortality on the basis of hard
      copy and digital publications in Russian and English in 1990-2016. It is
      established that air pollution by tiny particles of different origin results in a
      reliable increasing of risk of premature death independently of level of economic
      development and geographical positioning of country. In European countries this
      occurrence conditions shortage of of life-span on 8-13 months. The industrial
      factors are a cause of about 30% of involuntary occupational traumas. The
      limitation of access to clear drinking water specific to developing countries
      conditions death of more than 3 million people annually. The impact of waves of
      cold and heat on mortality depends on particular region, their duration and
      intensity, level of economic development of country, social economic conditions
      and age of particular groups of population and is estimated in 1-16% of
      additional deaths. The global climate warming is associated with decreasing of
      level of mortality. the negative impact of environment is increased by residing
      in underdeveloped regions, lower social economic status, lower level of
      education, population density, shortcomings of architecture and public space, the
      factors of environment play a significant role in population mortality. As
      regards their impact an uncertainty exists: it is quite difficult to separate an
      impact of single factor. So, different approaches are applied in different
      studies.

PMID- 29634863
TI  - [The Problems of Statistical Registration of Mortality Because of External Causes
      in Russia].
AB  - In Russia, the level of mortality of class of external causes in general and of
      particular cause within this class two-fold exceeds similar levels of these
      indices in the developed countries. The actual publications analyzing medical
      death certificates emphasize underestimation of levels of mortality because of
      such external causes as murders, suicides, alcohol intoxications, etc. and their
      transfer to latent form. In this connection, the topic of external causes was
      chosen to be a purpose of interviewing leading specialists in the field of
      demography, statistics and medicine. On the basis of analysis of opinions of
      experts, the issues of quantitative and qualitative statistical registrations of
      mortality because of external causes were considered. According opinion of
      experts, the external causes' statistic is to be published in concordance with
      the ICD-10. On the basis of the short list of ICD-10 the total scale of losses
      because of mortality of class of external causes and their kinds are clearly
      demonstrated. However, an in-depth analysis of mortality the detailed elaboration
      of the short list of ICD-10 is inadequate. The experts also considered both the
      causes of increasing of such a set of external causes as injuries with uncertain
      intentions and the means of decreasing level of mortality because of these causes
      including the main ones - changes of requirements to fill and procedure to issue
      death certificates. The experts considered too the legislative consolidation of
      regulation that inquest is to be initiated on the basis of application, report of
      offense but not the procedural standard concerning institution of prosecution and
      cardinal amelioration of the system of forensic expertise.

PMID- 29634864
TI  - [The Problems of Statistical Registration of Mortality Because of External Causes
      in Russia].
AB  - The physical accessibility of pharmaceuticals considering space-time factors and
      assortment accessibility is minutely considered on the example of the Sakhalin
      oblast. The conclusions considering universality of factors of accessibility and
      availability in every subject are made emphasizing necessity of characteristics
      to be taking into account. The analysis of factors of accessibility in the
      subject permits to establish risk zones preventing accessibility of
      pharmaceutical for population.

PMID- 29634865
TI  - [The Sociological Aspects of Development of Organization and Enhancement of
      Quality of Hospital Medical Care of Patients with Tuberculosis].
AB  - The specially developed questionnaire on studying opinions of physician
      phthisiatrician concerning hospital medical care of patients with tuberculosis
      was applied to survey sampling of 58 physicians phthisiatricians. The questions
      of questionnaire related to analysis of efficiency of hospital treatment of
      patients with tuberculosis, satisfaction with consultative and diagnostic
      activities, support with pharmaceuticals, discovering measures permitting to
      increase commitment of patients to treatment in conditions of hospital.

PMID- 29634866
TI  - [The Medical Social Characteristics of Rural Women].
AB  - The article presents the results of medical social characteristics of rural women
      aged from 20 to 60 years (average age is 44.6+-1.2 years). One third of them have
      secondary special education, 75% are married, 46% are working mainly in
      agricultural sector. Out of all working women 25.8% are exposed to unfavorable
      industrial factors, 20.3% are working in areas related to intensive labor
      processes. In 77.3% of respondents there is no centralized water supply and
      sewerage in home accommodations and there is no gas heating in 45.4% of
      respondents. About half of all surveyed women mentioned environmental pollution
      with livestock, poultry keeping and farm enterprises waste. The low level of
      living was noted more than 80% of respondents. more than 70% suffer from improper
      feeding and 46% have overweight. The rate of occurrence of chronic diseases made
      up to 212.3 per 100 examined women. In the structure of morbidity diseases of
      blood circulation system made up to 28.2%. The health self-estimate of women
      demonstrated that 2.1% of women consider their health as excellent, 11.3% - as a
      good one, 54.4% as a satisfactory one and 32.2% as a bad one.

PMID- 29634867
TI  - [The Morbidity of Students Conditioned by Diet Character in Modern Condition of
      Education].
AB  - The article considers characteristics of nervous psychic adaptation, morbidity
      and character of diet of students of the Russian state social university. The
      main incentives of combination of university studies and work are analyzed. The
      impact of combining of studies and work, regimen and diet quality on health are
      investigated. The psychological studies were implemented using computerized
      techniques of psychological testing and data collection with blank technique. The
      morbidity of students was discovered using questionnaire. It is established that
      students combining studies and work, have optimal indices of nervous psychic
      adaptation. however, level of their morbidity is twice higher than morbidity of
      students not combining studies and work. The analysis of regimen and diet
      character of students established deviations in regimen and structure of diet.
      The ration of proteins, fats and carbohydrates in day ration of students was
      imbalanced (1.0:1.4:6.1) at the expense of surplus of content of fat and
      especially carbohydrates that afterwards can results in development of diseases
      related to irregular diet.

PMID- 29634868
TI  - [About Development of Programs of Struggle with Tobacco Smoking in Medical
      Workers].
AB  - The article presents a review of prevalence of smoking among physicians and
      medical nurses suffering from nicotine dependence. The most of smoking medical
      workers began to smoke already during student years. they don't relate their
      diseases with smoking. The incomplete awareness of true causes of one's own
      diseases is manifested in ignoring preventive activities and healthy life-style.
      The actuality of necessity of development of program of prevention tobacco
      dependence in medical workers suffering from tobacco dependence is demonstrated.

PMID- 29634869
TI  - [The Actual Legal and Organizational Problems of Licensing of Military Medical
      Expertise].
AB  - The article presents analysis of problems of organization of functioning of
      military medical commissions in the light of implementation of complex of
      activities related to licensing of military medical expertise as a type of
      medical activity. The conceptual definitions and main legislative acts regulating
      procedures of licensing of the given type of expertise are considered. The
      characteristics of functioning of military medical expertise in actual conditions
      of Russia, including experience of Moscow and the Moskovskaia oblast are
      established.

PMID- 29634870
TI  - [On Day and Night Teams of Emergency Medical Care].
AB  - The article considers the results of sociological survey of patients related to
      functioning of day and night teams of emergency medical care.Out of all
      respondents, 97.9% were fully satisfied of functioning of team of emergency
      medical care. As cause of calling emergency medical care 57.5% of respondents
      mentioned instant acute disease, 21.5% - exacerbation of chronic disease. Out of
      number of called because of exacerbation of chronic disease 77% prefer emergency
      medical care over visit to territorial polyclinic. The received material testify
      that emergency medical care service is used by population as an alternative to
      out-patient polyclinic that indicates necessity of further activities on
      development of organization of emergency medical care.

PMID- 29634871
TI  - [The Efficiency of Implementation of Detailed Diary of Examination in Electronic
      Medical Record in Municipal Polyclinic].
AB  - The evaluation was carried out concerning efficiency of implementation of
      formalized and detailed form of diary of physician examination in the structure
      of electronic medical record in conditions of municipal polyclinic. The optimal
      direction of modernization of medical record was established as a formalization
      and detalization of patterns of of records in electronic form. It is demonstrated
      that implementation of such a form promotes more qualitative formatting and
      increases quality of medical care in general including increasing of percentage
      of positive outcomes of disease.

PMID- 29634872
TI  - [The Role of Physician In Enhancement of Rehabilitation of Disabled Children].
AB  - The national and international experience of rehabilitation of disabled children
      was investigated. On the basis of monitoring data problem of increasing of number
      of children with diagnosis of infantile cerebral paralysis, including necessity
      of development of new methods of their rehabilitation was established. The
      comparative dynamics of nosology of disabled children permitted to detect
      diseases of nervous system and congenital abnormalities (malformations),
      deformations and chromosomal disorders, psychological disorders and behavioral
      disorders mostly specific for urban and rural area. The model of institutional
      environment of rehabilitation of disabled children was developed including system
      of formal (state, legislative acts, health institutions, organizations of social
      support of population)and non-formal (public, non-commercial and social
      psychological organizations) institutions impacted by economic, social,legal and
      demographic factors. The role of physician is substantiated concerning increasing
      of quality of rehabilitation services: diagnostic of disordered functions,
      detection of optimal volume of medical, psychological and pedagogue activities in
      patients with severe speech disorders, motoric and and neuro-censorial disorders
      developed as a result of early organic damage of brain, neuro-infections,
      strokes, and other affection of brain. The adequate curative rehabilitative
      complex programs were developed of social everyday and social labor
      rehabilitation.

PMID- 29634873
TI  - [The School of S.P. Botkin: Vassili Nikolaievich Sirotinin (1855-1934)].
AB  - The article considers a number of characteristics of the scientific clinical
      school of S.P. Botkin. The exceptional significance of this school in the history
      of national medicine is emphasized. It is demonstrated that V.N. Sirotinin was
      the most outstanding of all his followers, the school leader and one of the
      leaders of the clinic of inner diseases in Russia during the first decades of XX
      century. The article presents the scientific biography of V.N. Sirotinin,
      including his emigration years. It is demonstrated that the issues of
      organization by V.N. Sirotinin of his own clinical school requires and additional
      investigation.

PMID- 29634874
TI  - [From the History of Class Philanthropy in Moscow: the T.G. Gurieva House of
      Charity of Poor People].
AB  - The article, for the first time on the basis of investigation of archive and
      published sources, presents the reconstruction of the picture of building and
      development of the T.G. Gurieva house of charity located in the territory of the
      A.V. Vishnevsky institute of surgery. The characteristics of functioning of this
      social institution during various historical stages are demonstrated. The history
      of class philanthropy in Moscow is supplemented by new information. The little
      known facts of functioning of one of the first specialized institutions of
      gerontological profile in the city are established. The general picture of
      development of the system population health care is reconstructed. The
      significance of the given object for national health care is established.

PMID- 29634875
TI  - [The Organization of Rural Physician Unit in the Stavropolskaia Gubernia, the
      Kubanskaia and Terskaia Oblast Before 1917].
AB  - The article considers becoming of rural health care in the Stavropolskaia
      gubernia, the Kubanskaia and Terskaia oblast prior to 1917. The statistic is
      presented concerning institutions of people's health.

PMID- 29634876
TI  - ProvenCare-Psoriasis: A disease management model to optimize care.
AB  - There are a variety of evidence-based treatments available for psoriasis. The
      transition of this evidence into practice is challenging. In this article, we
      describe the design of our disease management approach for Psoriasis
      (ProvenCare(r)) and present preliminary evidence of the effect of its
      implementation. In designing our approach, we identified three barriers to
      optimal care: 1) lack of a standardized and discrete disease activity measure
      within the electronic health record, 2) lack of a system-wide, standardized
      approach to care, and 3) non-uniform financial access to appropriate non
      pharmacologic treatments. We implemented several solutions, which collectively
      form our approach. We standardized the documentation of clinical data such as
      body surface area (BSA), created a disease management algorithm for psoriasis,
      and aligned incentives to facilitate the implementation of the algorithm. This
      approach provides more coordinated, cost effective care for psoriasis, while
      being acceptable to key stakeholders. Future work will examine the effect of the
      implementation of our approach on important clinical and patient outcomes.

PMID- 29634877
TI  - Peer reviews: the dreaded rejection.
AB  - This commentary considers the reasons for rejection of manuscripts during the
      peer-review process. Poor methodology, inappropriate statistical analysis,
      irrelevance, and technical errors are cited frequently as motives for manuscript
      rejection. Guidance, such as selecting an applicable journal, conducting a
      rigorous study, and writing efficiently, is provided for authors to prevent
      initial rejection. Researchers are reassured that rejection is a common
      consequence of peer-review and subsequent submissions to other journals are often
      successful publications.

PMID- 29634878
TI  - Perforating osteoma cutis: case report and literature review of patients with a
      solitary perforating osteoma cutis lesion.
AB  - Osteoma cutis, the development of bone in the dermis and/or subcutaneous fat, can
      occur as either a primary or secondary condition. Perforating osteoma cutis is
      rare. A man with a solitary lesion of perforating osteoma cutis is described and
      the features of individuals with a single perforating osteoma cutis skin lesion
      are reviewed. A solitary lesion of either primary or secondary perforating
      osteoma cutis has only been observed in two men and one woman; the lesions had
      been present from less than one month to 19 or 20 years prior to establishing the
      diagnosis. The lesion was either located on the forehead (two men) or the breast
      (one woman). The erythematous (two lesions) or flesh-colored nodules ranged in
      size from 8*8 millimeters to 1.5*0.5 centimeters. Each had epidermal perforation
      by bone through a central area that was either crateriform or crusted or
      keratotic. The clinical differential diagnosis included keratoacanthoma,
      phlebolith, pilomatricoma, pilomatrical carcinoma, and squamous cell carcinoma.
      The perforating osteoma cutis lesion was successfully treated with either
      excision or shave biopsy without recurrence at either 10 or 12-months follow-up.

PMID- 29634880
TI  - Mycoplasma-induced pustulosis with perifollicular involvement.
AB  - Mycoplasma pneumoniae-induced rash and mucositis (MIRM) is a disease
      characterized by mucosal involvement with variable cutaneous manifestations
      induced by M. pneumoniae infection. Previously reported rash morphologies include
      vesiculobullous, targetoid, papular, macular, and morbilliform lesions.
      Pustulosis is a rare presentation of MIRM that has been described only once
      before in the literature to our knowledge. We report a case of a 13-year-old boy
      presenting with a pustular skin eruption induced by Mycoplasma infection. Ours'
      is the second report of MIRM, to our knowledge, presenting with pustulosis and
      the first, to our knowledge, to first to describe the histopathologic finding of
      perifollicular neutrophilic infiltration in MIRM.

PMID- 29634879
TI  - Kindler syndrome in a patient with colitis and primary sclerosing cholangitis:
      coincidence or association?
AB  - Kindler syndrome is a rare, autosomal recessive genodermatosis, caused by
      mutations in the FERMT1 gene. It is thought to be primarily a skin disease, but
      other organs may also be involved. We report a case of a novel mutation of FERMT1
      gene in a patient with a probable new phenotype of Kindler syndrome, including
      colitis and primary sclerosing cholangitis. A 42-year-old man, born to first
      cousin parents, was referred to our outpatient dermatology clinic with an unknown
      dermatosis since birth. He presented with neonatal blistering and developed
      photosensitivity and changes in skin pigmentation during childhood. Since the age
      of 20, he has had regular follow-up in the gastroenterology clinic, owing to
      esophageal stenosis, ulcerative colitis, and primary sclerosing cholangitis.
      Clinical examination revealed jaundice, poikiloderma, diffuse cigarette paper
      like atrophy on dorsal surfaces of the hands, and palmoplantar hyperkeratosis.
      Skin biopsy showed epidermal atrophy covered by orthokeratotic hyperkeratosis.
      DNA molecular analysis revealed FERMT1 homozygous mutation c.1179G>A, p.W393X,
      which has not been reported before. The intestinal phenotype of Kindler syndrome
      has already been defined previously. However, to the best of our knowledge, no
      other case of primary sclerosing cholangitis in a patient with Kindler syndrome
      has been reported.

PMID- 29634881
TI  - Thalidomide for the treatment of chronic refractory prurigo nodularis.
AB  - Prurigo nodularis (PN) is a highly pruritic skin condition that is caused by
      chronic scratching. It occurs in patients with chronic itch and is characterized
      by multiple hyperkeratotic papules and nodules. The pathogenesis of PN is
      unclear, but involves a complex interplay of numerous pathways including
      neurogenic and inflammatory factors. As such, PN is very difficult to treat and
      patients are often refractory to multiple medications before finding a treatment
      that is effective. We present a woman with a 20-year history of exuberant prurigo
      nodularis who failed multiple therapies, including dapsone, azathioprine,
      mycophenolic acid, prednisone, topical steroids, and phototherapy. She only
      obtained significant relief of chronic pruritus and lesion flattening with
      thalidomide 100mg daily. Thalidomide is an antipruritic and anti-inflammatory
      agent that has shown to be very effective in treating a variety of dermatologic
      conditions. However, its use today is limited by concerns for its teratogenic and
      neuropathic side effects. With strict adherence to medication protocols, these
      adverse effects can be minimized. As such, thalidomide should be considered for
      patients with refractory dermatologic conditions.

PMID- 29634882
TI  - Genitogluteal porokeratosis in an HIV-positive man: a case report and review of
      the literature on genital porokeratosis.
AB  - Genitogluteal porokeratosis is a disorder of keratinization that may present in
      men in their fourth decade of life. We describe a 52-year-old human
      immunodeficiency virus (HIV)-positive man with history of anal squamous cell
      carcinoma who developed verrucous lesions on the buttocks and genitals. The
      buttock lesions presented shortly after radiotherapy for anal carcinoma a decade
      prior, whereas the genital lesions presented three months prior in areas treated
      with injectable medication for erectile dysfunction. Skin biopsy revealed a
      cornoid lamella, leading to the diagnosis of genitogluteal porokeratosis. The
      buttock lesions were treated with shave excision and the genital lesions were
      treated with topical agents. Using the PubMed database, a literature search was
      performed with combinations of the following key words: acuminata, condyloma,
      cornoid lamella, genital, genitogluteal, HIV, penile, porokeratosis, verrucous,
      vulvar. The generated papers and their references were reviewed. To the best of
      our knowledge, we present the first reported case of genitogluteal porokeratosis
      in an HIV-positive man. Notably, these lesions developed in sites of prior
      radiation or injection. This condition should be included in the differential
      diagnosis of chronic lesions of the genitals and buttocks in patients with HIV
      and/or history of radiation treatment and/or trauma to the genitogluteal region.

PMID- 29634883
TI  - Persistent perpendicular pigmentation: a peculiar but specific type of persistent
      nevus.
AB  - Persistent nevi are commonly encountered in clinical and dermatopathology
      practice. Although they may mimic melanoma on clinical presentation as well as
      microscopic review, they behave in a benign fashion and are not associated with
      more aggressive behavior than the original nevus. Persistent nevi may exhibit
      asymmetry and irregular features that prompt concern for melanoma. However, the
      relative circumscription and restriction of pigment to the surgical scar provides
      a valuable clue to diagnosis. Some persistent nevi may have a linear pattern when
      they are confined to a widening scar. In this situation, the pigment spreads
      along the lines of skin tension (Langer lines). This unique pattern can be easily
      identified and should be a reassuring finding. We present a case of persistent
      nevus with a striking perpendicular pigmentation confined to the scar; the
      clinical and histologic features of persistent nevi are reviewed.

PMID- 29634884
TI  - An amelanotic nail bed melanoma presenting as persistent onychodystrophy.
AB  - Nail apparatus melanomas are rare and may present with a wide variety of clinical
      presentations. In particular, the amelanotic subtype can pose a diagnostic
      challenge, often leading to a poor prognosis related to a delayed diagnosis. We
      report a 69-year-old man with an unusual subungual amelanotic melanoma presenting
      as a persistent single nail dystrophy that was repeatedly treated as
      onychomycosis. Owing to the delayed diagnosis of the melanoma and to minimize
      recurrence risk, the patient underwent a partial amputation of his left thumb.

PMID- 29634885
TI  - A case of segmental Darier disease treated with doxycycline monotherapy.
AB  - Darier disease is a rare autosomal dominant disorder that results from a mutation
      in the gene coding for the endoplasmic reticulum membrane calcium pump Ca2+
      ATPase type 2 (SERCA2), leading to compromised intercellular adhesion. Patients
      typically present in the first two decades of life with keratotic, greasy papules
      in a seborrheic distribution. Segmental Darier disease is a variant with
      localized disease that follows Blaschko lines. Treatment options include topical
      and systemic agents including corticosteroids, retinoids, and antibiotics. We
      present a 67-year-old woman who came to our clinic with segmental Darier disease
      recalcitrant to topical therapy. Owing to cost and side effect profile, the
      patient declined treatment with oral retinoids. Doxycycline 100mg daily was
      started with significant improvement. Tetracyclines both chelate and assist
      calcium to cross membranes. This mechanism may correct the cellular calcium
      imbalance present in Darier disease. In addition, tetracyclines have been shown
      to inhibit metalloproteinase 9, an important part of Darier disease pathogenesis.
      Owing to its favorable side effect profile, further investigation is warranted to
      establish doxycycline as a more widely utilized treatment option for Darier
      disease.

PMID- 29634886
TI  - Temozolomide-induced inflammation of disseminated superficial actinic
      porokeratosis.
AB  - We report a case of temozolomide (TMZ)-induced inflammation of disseminated
      superficial actinic porokeratosis (DSAP), an uncommon and pre-malignant cutaneous
      disorder. Dermatologists and oncologists should be aware of this cutaneous
      eruption of DSAP associated with TMZ to prevent the discontinuation of effective
      medical therapy in cancer patients.

PMID- 29634887
TI  - Cutaneous complication of perinatal hypoxia.
AB  - Subcutaneous fat necrosis of the newborn is an uncommon, transient, and self
      healing panniculitis, mostly affecting term newborns with perinatal
      complications. The authors present a case of a female full-term neonate, born
      from an uncomplicated pregnancy, admitted into the neonatology unit 5 hours after
      delivery because of refractory multifocal seizures in the context of hypoxic
      ischemic encephalopathy. Nine days after birth, indurated and erythematous
      nodules and plaques were noted on the left arm and back. Skin biopsy was
      compatible with subcutaneous fat necrosis of the newborn. Laboratory evaluation
      including serum calcium showed normal values. No treatment was initiated. This
      entity generally follows an uncomplicated course. However, there are important
      complications for which the patient must be regularly monitored, including
      thrombocytopenia, hypoglycemia, hypertriglyceridemia, and most importantly,
      hypercalcemia. Patients should have serial serum calcium determinations for up to
      6 months after the appearance of the skin lesions. The early diagnosis and prompt
      treatment of hypercalcemia are essential to prevent severe complications.

PMID- 29634888
TI  - Circumscribed palmar hypokeratosis.
AB  - Circumscribed palmar hypokeratosis (CPH) is a benign dermatologic condition
      characterized by local thinning of the stratum corneum. Herein, we present a 52
      year-old woman who presented with an asymptomatic pink depressed papule on the
      right palm. This was treated with clobetasol 0.05% topically twice a day with no
      improvement.

PMID- 29634889
TI  - Infiltrative basal cell carcinoma mimicking tinea corporis.
AB  - The diagnosis of infiltrative basal cell carcinoma (BCC) can be delayed owing to
      its often subtle clinical findings. A 90-year-old woman presented with an
      asymptomatic annular pink plaque on her left shin that was clinically diagnosed
      as tinea corporis. After years of not responding to topical anti-fungal therapy,
      biopsies confirmed a diagnosis of infiltrative BCC. We discuss the differential
      diagnosis of the case, the difficulties in identifying infiltrative BCC, and the
      pathologic features of infiltrative BCC.

PMID- 29634890
TI  - Vulvar syringomas as a part of nonfamilial generalized eruptive form: Unusual
      lesions leading to pseudohyper-trophy of the labia majora.
AB  - We present a case of eruptive generalized syringoma with vulvar involvement. This
      case is unique in terms of being a nonfamilial, linear variant, leading to
      pseudohypertrophy of the labia majora.

PMID- 29634891
TI  - Capillary hemangioma associated with dermal atrophy masquerading as a deep fungal
      infection.
AB  - Hemangiomas are benign vascular neoplasms which arise in early adulthood. Herein
      we present a 79-year-old woman with a hemangioma of the lower flank masquerading
      as a cutaneous manifestation of a systemic fungal infection upon initial
      histological analysis. Decreased elastin and collagen within the lesion likely
      accounted for the clumping and splaying of the capillaries into "hyphae-like"
      structures. Loss of dermal elastic tissue and collagen apparently concentrated
      the capillary proliferation into an unusual morphology mimicking the hyphal
      structures. Through additional staining methods the lesion was confirmed to be an
      unusual presentation of a capillary hemangioma.

PMID- 29634892
TI  - Secukinumab shows significant efficacy in two patients with difficult-to-treat
      areas of psoriasis: a Greek experience.
AB  - Psoriasis is one of the most frequently occurring chronic inflammatory skin
      diseases. There are some specialized regions of the body that are considered
      difficult to treat. Secukinumab is a human monoclonal immunoglobulin G antibody
      that blocks the interleukin 17A ligand and has been shown to be highly
      efficacious in treating moderate-to-severe psoriasis. We studied two Greek
      patients, one with scalp psoriasis and the other with palmoplantar psoriasis,
      both resistant to treatment. Patients were treated with secukinumab and efficacy
      and safety were recorded. The patient with severe, refractory palmoplantar
      psoriasis achieved complete clearance at the end of the 4-week treatment period
      with secukinumab. The patient with moderate to severe, chronic scalp psoriasis
      was successfully treated with secukinumab, obtaining complete clearance of
      symptoms and remission of disease after approximately 16 weeks. In both cases
      clinical response was maintained through week 52. Secukinumab has been shown to
      be highly efficacious in the treatment of psoriasis of specific anatomical sites
      with an acceptable safety profile.

PMID- 29634893
TI  - Cutaneous Staphylococcus lugdunensis infection: an emerging bacterial pathogen.
AB  - Staphylococcus lugdunensis is a part of the normal skin flora. However, this
      organism can be a pathogen in certain situations such as advanced age or
      immunosuppression. Further study regarding situations in which this bacterium
      becomes a pathogen is warranted.

PMID- 29634894
TI  - Ectopic intestinal mucosa implanted on the perianal skin of a patient with Crohn
      disease.
AB  - Intestinal mucosa implanted in skin is an exceedingly rare occurrence.
      Implantations are thought to occur during the creation of ostomy sites or other
      surgical procedures in which suture goes through bowel mucosa and then skin.
      Current ostomy literature reports this as a very uncommon complication. We
      present a 54-year-old man diagnosed with Crohn disease with severe perianal
      involvement who was referred to our outpatient clinic because of two persistent
      perianal cutaneous ulcerations. He previously underwent several interventions to
      drain complex perianal fistulas and abscesses, the last of them involved placing
      seton stitches to ensure continuous draining during the healing process. Physical
      examination revealed two painful ulcerations with bleeding on contact. A skin
      biopsy was performed, revealing ectopic intestinal mucosa with crypts, villi, and
      goblet cells. Perianal ulcerations characteristic of Crohn disease might be
      difficult to differentiate from ectopic implant of bowel mucosa secondary to a
      surgical procedure in the perianal area. Therefore, we believe a high degree of
      suspicion and skin biopsy are key to the diagnosis.

PMID- 29634895
TI  - Gel manicures and ultraviolet A light: A call for patient education.
AB  - Gel manicures have become a popular beauty trend in recent years. The specially
      formulated nail polish must undergo curing under light-based units. The majority
      of these curing lamps emit high-intensity ultraviolet A, which can cause skin
      damage and increase the risk for skin cancers. Incorporating relevant information
      in patient education endeavors can help them practice avoidance, apply broad
      spectrum sunscreen prior, or use nitrile exam gloves in order to prevent
      photoaging and skin cancer resulting from these procedures.

PMID- 29634896
TI  - Jaundice in the emergency department: meeting the challenges of diagnosis and
      treatment [digest].
AB  - There are approximately 52,000 visits a year to emergency departments for
      patients presenting with jaundice. While many of these patients will not have
      immediately life-threatening pathology, it is essential that the emergency
      clinician understands the pathophysiology of jaundice, as this will guide the
      appropriate workup to detect critical diagnoses. Patients who present with
      jaundice could require intravenous antibiotics, emergent surgery, and, in severe
      cases, organ transplantation. This issue will focus on the challenge of
      evaluating and treating the jaundiced patient in the ED using the best available
      evidence from the literature. [Points & Pearls is a digest of Emergency Medicine
      Practice.].

PMID- 29634897
TI  - Pediatric emergency transport: communication and coordination are key to
      improving outcomes [digest].
AB  - Pediatric patients who are critically ill or who require urgent subspecialty
      evaluation or specialized imaging, equipment, or procedures must often be
      transferred to tertiary care centers. The safe execution of interfacility
      transfer requires the coordination between the facility healthcare teams at each
      end of the transfer as well as the transport team. This issue discusses the
      process of interfacility transfer, the required services, the role of the
      emergency clinician, the role of the pediatric transport team, and the commonly
      used diagnostic studies and treatment needed during interfacility transfers of
      pediatric patients. [Points & Pearls is a digest of Pediatric Emergency Medicine
      Practice].

PMID- 29634898
TI  - Targeting Tyrosinase: Development and Structural Insights of Novel Inhibitors
      Bearing Arylpiperidine and Arylpiperazine Fragments.
AB  - The inhibition of tyrosinase (Ty, EC 1.14.18.1) represents an efficient strategy
      of decreasing melanogenesis and skin hyperpigmentation. A combination of
      crystallographic and docking studies on two different tyrosinases, that from
      Bacillus megaterium (TyBm) and that from a mushroom (TyM), has contributed to
      increasing our knowledge about their structural information and translating that
      information to the most druggable human Ty (TyH) isozyme. In particular, we
      designed and synthesized a series of 1-(4-fluorobenzyl)piperazine and 1-(4
      fluorobenzyl)piperidine derivatives showing inhibitory activities on TyM at
      micromolar ranges and more potency than that of the reference compound, kojic
      acid. The crystal structures of TyBm with inhibitor 3 (IC50 value of 25.11 MUM)
      and 16 (IC50 value of 5.25 MUM) were solved, confirming the binding poses
      hypothesized by in silico studies and revealing the main molecular determinants
      for the binding recognition of the inhibitors.

PMID- 29634899
TI  - Supramolecular Strategy Based on Conjugated Polymers for Discrimination of Virus
      and Pathogens.
AB  - A conjugated polymer-based supramolecular system is designed for discrimination
      of virus and microbes. The supramolecular system is composed of cationic
      polythiophene derivative (PT) and barrel-shaped macrocyclic molecular
      cucurbit[7]uril (CB[7]). Because PT and PT/CB[7] complexes possess different
      interaction manners toward virus and microbes, the rapid and simple
      discrimination of virus and microbes was realized through polymer fluorescence
      intensity change assisting with standard linear discriminant analysis (LDA). The
      supramolecular strategy would expand the idea of designing biological probes and
      further promote the extensive application of conjugated polymer materials in
      biosensor field.

PMID- 29634900
TI  - Increased Acid Dissociation at the Quartz/Water Interface.
AB  - As shown by a quite significant amount of literature, acids at the water surface
      tend to be "less" acid, meaning that their associated form is favored over the
      conjugated base. What happens at the solid/liquid interface? In the case of the
      silica/water interface, we show how the acidity of adsorbed molecules can instead
      increase. Using a free energy perturbation approach in combination with
      electronic structure-based molecular dynamics simulations, we show how the
      acidity of pyruvic acid at the quartz/water interface is increased by almost two
      units. Such increased acidity is the result of the specific microsolvation at the
      interface and, in particular, of the stabilization of the deprotonated form by
      the silanols on the quartz surface and the special interfacial water layer.

PMID- 29634901
TI  - Engineered and Environmental Controls of Microbial Denitrification in Established
      Bioretention Cells.
AB  - Bioretention cells (BRCs) are effective tools for treating urban stormwater, but
      nitrogen removal by these systems is highly variable. Improvements in nitrogen
      removal are hampered by a lack of data directly quantifying the abundance or
      activity of denitrifying microorganisms in BRCs and how they are controlled by
      original BRC design characteristics. We analyzed denitrifiers in twenty-three
      BRCs of different designs across three mid-Atlantic states (MD, VA, and NC) by
      quantifying two bacterial denitrification genes ( nirK and nosZ) and potential
      enzymatic denitrification rates within the soil medium. Overall, we found that
      BRC design factors, rather than local environmental variables, had the greatest
      effects on variation in denitrifier abundance and activity. Specifically,
      denitrifying populations and denitrification potential increased with organic
      carbon and inorganic nitrogen concentrations in the soil media and decreased in
      BRCs planted with grass compared to other types of vegetation. Furthermore, the
      top layers of BRCs consistently contained greater concentrations and activity of
      denitrifying bacteria than bottom layers, despite longer periods of saturation
      and the presence of permanently saturated zones designed to promote
      denitrification at lower depths. These findings suggest that there is still
      considerable potential for design improvements when constructing BRCs that could
      increase denitrification and mitigate nitrogen export to receiving waters.

PMID- 29634903
TI  - Unbiased Proteomic Study of the Axons of Cultured Rat Cortical Neurons.
AB  - The axon is a long projection connecting a neuron to its targets. Here, the axons
      of cultured rat cortical neurons were isolated with micropatterned chips that
      enable the separation of axons from their cell bodies. Proteins extracted from
      isolated axons and whole neurons were subjected to analyses using two-dimensional
      liquid chromatography-tandem mass spectrometry (2D-LC-MS/MS) analyses without and
      with stable isotope dimethyl labeling, resulting in the identification of >2500
      axonal proteins and 103 axon-enriched proteins. A strong correlation exists
      between the abundances of axonal proteins and their counterparts in whole
      neurons. The proteomic results confirm the axonal protein constituents of the
      subcellular structures documented in earlier electron microscopic studies.
      Cortical axons have proteins that are components of machineries for protein
      degradation and the synthesis of soluble, membrane, and secretory proteins,
      although axons lack conventional Golgi apparatus. Despite the fact that axons
      lack nucleus, nuclear proteins were identified, and 67 of them were found
      enriched in axons. Some of the results obtained by the MS-based studies were
      validated by quantitative Western blotting and immunofluorescence staining
      analyses. The results represent the first comprehensive description of the axonal
      protein landscape. The MS proteomics data are available via ProteomeXchange with
      identifier PXD005527.

PMID- 29634902
TI  - The Excess Chemical Potential of Water at the Interface with a Protein from End
      Point Simulations.
AB  - We use end point simulations to estimate the excess chemical potential of water
      in the homogeneous liquid and at the interface with a protein in solution. When
      the pure liquid is taken as the reference, the excess chemical potential of
      interfacial water is the difference between the solvation free energy of a water
      molecule at the interface and in the bulk. Using the homogeneous liquid as an
      example, we show that the solvation free energy for growing a water molecule can
      be estimated by applying UWHAM to the simulation data generated from the initial
      and final states (i.e., "the end points") instead of multistate free energy
      perturbation simulations because of the possible overlaps of the configurations
      sampled at the end points. Then end point simulations are used to estimate the
      solvation free energy of water at the interface with a protein in solution. The
      estimate of the solvation free energy at the interface from two simulations at
      the end points agrees with the benchmark using 32 states within a 95% confidence
      interval for most interfacial locations. The ability to accurately estimate the
      excess chemical potential of water from end point simulations facilitates the
      statistical thermodynamic analysis of diverse interfacial phenomena. Our focus is
      on analyzing the excess chemical potential of water at protein receptor binding
      sites with the goal of using this information to assist in the design of tight
      binding ligands.

PMID- 29634904
TI  - Insight into Multiple and Multilevel Structures of Biochars and Their Potential
      Environmental Applications: A Critical Review.
AB  - Biochar is the carbon-rich product of the pyrolysis of biomass under oxygen
      limited conditions, and it has received increasing attention due to its multiple
      functions in the fields of climate change mitigation, sustainable agriculture,
      environmental control, and novel materials. To design a "smart" biochar for
      environmentally sustainable applications, one must understand recent advances in
      biochar molecular structures and explore potential applications to generalize
      upon structure-application relationships. In this review, multiple and multilevel
      structures of biochars are interpreted based on their elemental compositions,
      phase components, surface properties, and molecular structures. Applications such
      as carbon fixators, fertilizers, sorbents, and carbon-based materials are
      highlighted based on the biochar multilevel structures as well as their structure
      application relationships. Further studies are suggested for more detailed
      biochar structural analysis and separation and for the combination of macroscopic
      and microscopic information to develop a higher-level biochar structural design
      for selective applications.

PMID- 29634906
TI  - Stepped Propane Adsorption in Pure-Silica ITW Zeolite.
AB  - Gas adsorption over zeolites is at the basis of important applications of this
      class of microporous crystalline solids, notably as separation media and
      catalysts, but it may also be complex and not straightforward to understand. Here
      we report that for temperature below 323 K propane adsorption on the small-pore
      pure-silica zeolite ITW exhibits a clear step (pseudosaturation). This is absent
      in the case of propene and the other small linear alkanes. An intermediate
      plateau, clearly observed in the 293 K isotherm, always occurs when one molecule
      of propane is loaded in every other cage, i.e., at half-saturation. The
      simulation results show a swelling of the ITW structure upon propane adsorption.
      The strong dependence of available pore volume on the adsorbate loading level
      implies that adsorption cannot occur on the void structure while saturation can
      only be reached on highly loaded structures. To account for this unprecedented
      adsorption phenomenon, we propose the term "guest-modulated effect".

PMID- 29634905
TI  - A Triazole Disulfide Compound Increases the Affinity of Hemoglobin for Oxygen and
      Reduces the Sickling of Human Sickle Cells.
AB  - Sickle cell disease is an inherited disorder of hemoglobin (Hb). During a sickle
      cell crisis, deoxygenated sickle hemoglobin (deoxyHbS) polymerizes to form fibers
      in red blood cells (RBCs), causing the cells to adopt "sickled" shapes. Using
      small molecules to increase the affinity of Hb for oxygen is a potential approach
      to treating sickle cell disease, because oxygenated Hb interferes with the
      polymerization of deoxyHbS. We have identified a triazole disulfide compound
      (4,4'-di(1,2,3-triazolyl)disulfide, designated TD-3), which increases the
      affinity of Hb for oxygen. The crystal structures of carboxy- and deoxy-forms of
      human adult Hb (HbA), each complexed with TD-3, revealed that one molecule of the
      monomeric thiol form of TD-3 (5-mercapto-1H-1,2,3-triazole, designated MT-3)
      forms a disulfide bond with beta-Cys93, which inhibits the salt-bridge formation
      between beta-Asp94 and beta-His146. This inhibition of salt bridge formation
      stabilizes the R-state and destabilizes the T-state of Hb, resulting in reduced
      magnitude of the Bohr effect and increased affinity of Hb for oxygen. Intravenous
      administration of TD-3 (100 mg/kg) to C57BL/6 mice increased the affinity of
      murine Hb for oxygen, and the mice did not appear to be adversely affected by the
      drug. TD-3 reduced in vitro hypoxia-induced sickling of human sickle RBCs. The
      percentage of sickled RBCs and the P50 of human SS RBCs by TD-3 were inversely
      correlated with the fraction of Hb modified by TD-3. Our study shows that TD-3,
      and possibly other triazole disulfide compounds that bind to Hb beta-Cys93, may
      provide new treatment options for patients with sickle cell disease.

PMID- 29634907
TI  - Synthesis and Unique Optical Properties of Selenophenyl BODIPYs and Their Linear
      Oligomers.
AB  - A series of selenophene-substituted boron-dipyrrin (BODIPY) monomers and
      selenophene-linked BODIPY oligomers was synthesized. The synthesized BODIPYs show
      good absorption/emission properties in the red to near-infrared region.
      Furthermore, some of the selenophenyl BODIPYs are not only useful fluorophores
      but also good photosensitizers to produce singlet oxygen.

PMID- 29634908
TI  - Understanding the Mechanism of SiC Plasma-Enhanced Chemical Vapor Deposition
      (PECVD) and Developing Routes toward SiC Atomic Layer Deposition (ALD) with
      Density Functional Theory.
AB  - Understanding the mechanism of SiC chemical vapor deposition (CVD) is an
      important step in investigating the routes toward future atomic layer deposition
      (ALD) of SiC. The energetics of various silicon and carbon precursors reacting
      with bare and H-terminated 3C-SiC (011) are analyzed using ab initio density
      functional theory (DFT). Bare SiC is found to be reactive to silicon and carbon
      precursors, while H-terminated SiC is found to be not reactive with these
      precursors at 0 K. Furthermore, the reaction pathways of silane plasma fragments
      SiH3 and SiH2 are calculated along with the energetics for the methane plasma
      fragments CH3 and CH2. SiH3 and SiH2 fragments follow different mechanisms toward
      Si growth, of which the SiH3 mechanism is found to be more thermodynamically
      favorable. Moreover, both of the fragments were found to show selectivity toward
      the Si-H bond and not C-H bond of the surface. On the basis of this, a selective
      Si deposition process is suggested for silicon versus carbon-doped silicon oxide
      surfaces.

PMID- 29634909
TI  - Stable Dispersions of Covalently Tethered Polymer Improved Graphene Oxide
      Nanoconjugates as an Effective Vector for siRNA Delivery.
AB  - Conjugates of poly(amidoamine) (PAMAM) with modified graphene oxide (GO) are
      attractive nonviral vectors for gene-based cancer therapeutics. GO protects siRNA
      from enzymatic cleavage and showed reasonable transfection efficiency along with
      simultaneous benefits of low cost and large scale production. PAMAM is highly
      effective in siRNA delivery but suffers from high toxicity with poor in vivo
      efficacy. Co-reaction of GO and PAMAM led to aggregation and more importantly,
      have detrimental effect on stability of dispersion at physiological pH preventing
      their exploration at clinical level. In the current work, we have designed,
      synthesized, characterized and explored a new type of hybrid vector (GPD), using
      GO synthesized via improved method which was covalently tethered with
      poly(ethylene glycol) (PEG) and PAMAM. The existence of covalent linkage,
      relative structural changes and properties of GPD is well supported by Fourier
      transform infrared (FTIR), UV-visible (UV-vis), Raman, X-ray photoelectron (XPS),
      elemental analysis, powder X-ray diffraction (XRD), thermogravimetry analysis
      (TGA), dynamic light scattering (DLS), and zeta potential. Scanning electron
      microscopy (SEM), and transmission electron microscopy (TEM) of GPD showed
      longitudinally aligned columnar self-assembled ~10 nm thick polymeric
      nanoarchitectures onto the GO surface accounting to an average size reduction to
      ~20 nm. GPD revealed an outstanding stability in both phosphate buffer saline
      (PBS) and serum containing cell medium. The binding efficiency of EPAC1 siRNA to
      GPD was supported by gel retardation assay, DLS, zeta potential and
      photoluminescence (PL) studies. A lower cytotoxicity with enhanced cellular
      uptake and homogeneous intracellular distribution of GPD/siRNA complex is
      confirmed by imaging studies. GPD exhibited a higher transfection efficiency with
      remarkable inhibition of cell migration and lower invasion than PAMAM and
      Lipofectamine 2000 suggesting its role in prevention of breast cancer progression
      and metastasis. A significant reduction in the expression of the specific protein
      against which siRNA was delivered is revealed by Western blot assay. Furthermore,
      a pH-triggered release of siRNA from the GPD/siRNA complex was studied to provide
      a mechanistic insight toward unloading of siRNA from the vector. Current strategy
      is a way forward for designing effective therapeutic vectors for gene-based
      antitumor therapy.

PMID- 29634910
TI  - Determination of enantiomeric excess of some amino acids by second-order
      calibration of kinetic-fluorescence data.
AB  - In this investigation a new non-separative kinetic-spectroflourimetric method is
      proposed for the determination of lysine (lys), leucine (leu) and phenylalanine
      (phe) enantiomers as their o-phthaldialdehyde (OPA) derivatives in the presence
      of an optically active chiral thiol compound, 1-mercapto-2-propanol (MP). At
      ambient temperature and in the borate buffer media of pH 9.6, MP, OPA, as highly
      selective fluorogenic reagents, and amino acid (AA) enantiomers reacts with each
      other to yield two fluorescent diasteriomers of D and L-AA with maximum
      difference in fluorescence intensity at about 450 nm. To achieve information from
      the small spectral changes, the data are analyzed by Multivariate Curve
      Resolution Alternating Least Squares (MCR-ALS) method. Linear calibration curves
      are achieved to distinct D and L-lys, leu and phe in different mole ratios by
      applying appropriate constraints in MCR-ALS procedures. This is the first
      application of MCR-ALS in determination of enantiomeric excess (ee) using OPA/MP
      adduct as chiral reagent, which benefits from direct time dependent-fluorescence
      spectral analysis and does not require prior separation of chiral analytes. Both
      the cross-validated correlation coefficient (Q2) and root mean squares error of
      prediction (RMSEP) indicated satisfactory prediction ability of this method.

PMID- 29634911
TI  - Perioperative pregnancy interval, contraceptive counseling experiences, and
      contraceptive use in women undergoing bariatric surgery.
AB  - BACKGROUND: Reproductive-aged women represent about half of those undergoing
      bariatric surgery in the United States. Obstetric and bariatric professional
      societies recommend that women avoid pregnancy for 12-18 months postoperatively
      due to concern for increased pregnancy risks, and that providers should counsel
      women about these recommendations and their contraceptive options. However,
      knowledge about women's experience with perioperative counseling and
      postoperative contraceptive use is limited. OBJECTIVE: We sought to: (1)
      determine prevalence of perioperative contraceptive and pregnancy interval
      discussions among women who have recently undergone bariatric surgery; and (2)
      describe postoperative contraceptive use within the first year of surgery in this
      population. STUDY DESIGN: We performed a cross-sectional study of US women, aged
      18-45 years and recruited through Facebook, who underwent bariatric surgery
      within the last 24 months. RESULTS: We enrolled 363 geographically diverse women.
      Three-quarters recalled perioperative pregnancy or contraceptive discussions, the
      majority with a bariatric provider. Half felt it was "very important" to discuss
      these issues perioperatively, and 41% of those who reported discussions wished
      they had had more. Of the 66% of women who reported using contraception in the
      first 12 months postoperatively, 27% used oral contraceptives and 26% used an
      intrauterine device. One third of contraceptive users who had undergone Roux-en-Y
      gastric bypass, a combined restrictive-malabsorptive procedure, were using oral
      contraceptives. Perioperative contraceptive or pregnancy discussions were
      independently associated with increased postoperative contraceptive use (odds
      ratios, 2.5; 95% confidence interval, 1.5-4.3, P < .001). CONCLUSION: A
      substantial proportion of women who had undergone bariatric surgery reported
      having had no perioperative pregnancy or contraception counseling, and many women
      who had felt the discussions were insufficient. Those who had had perioperative
      discussions were more likely to use contraception postoperatively. Reproductive
      aged women should be routinely counseled perioperatively about pregnancy and
      contraception in the context of their reproductive desires, so they can make
      informed decisions about perioperative pregnancy prevention and contraceptive
      method use.

PMID- 29634912
TI  - Secondary gastric involvement of follicular lymphoma.

PMID- 29634913
TI  - Linitis plastica in excluded stomach after Roux-en-Y gastric bypass.

PMID- 29634914
TI  - Gastric metastasis from pancreatic neuroendocrine tumor.

PMID- 29634915
TI  - Additional Physical Therapy Services Reduce Length of Stay and Improve Health
      Outcomes in People With Acute and Subacute Conditions: An Updated Systematic
      Review and Meta-Analysis.
AB  - OBJECTIVE: To update a previous review on whether additional physical therapy
      services reduce length of stay, improve health outcomes, and are safe and cost
      effective for patients with acute or subacute conditions. DATA SOURCES:
      Electronic database (AMED, CINAHL, EMBASE, MEDLINE, Physiotherapy Evidence
      Database [PEDro], PubMed) searches were updated from 2010 through June 2017.
      STUDY SELECTION: Randomized controlled trials evaluating additional physical
      therapy services on patient health outcomes, length of stay, or cost
      effectiveness were eligible. Searching identified 1524 potentially relevant
      articles, of which 11 new articles from 8 new randomized controlled trials with
      1563 participants were selected. In total, 24 randomized controlled trials with
      3262 participants are included in this review. DATA EXTRACTION: Data were
      extracted using the form used in the original systematic review. Methodological
      quality was assessed using the PEDro scale, and the Grading of Recommendation
      Assessment, Development, and Evaluation approach was applied to each meta
      analysis. DATA SYNTHESIS: Postintervention data were pooled with an inverse
      variance, random-effects model to calculate standardized mean differences (SMDs)
      and 95% confidence intervals (CIs). There is moderate-quality evidence that
      additional physical therapy services reduced length of stay by 3 days in subacute
      settings (mean difference [MD]=-2.8; 95% CI, -4.6 to -0.9; I2=0%), and low
      quality evidence that it reduced length of stay by 0.6 days in acute settings
      (MD=-0.6; 95% CI, -1.1 to 0.0; I2=65%). Additional physical therapy led to small
      improvements in self-care (SMD=.11; 95% CI, .03-.19; I2=0%), activities of daily
      living (SMD=.13; 95% CI, .02-.25; I2=15%), and health-related quality of life
      (SMD=.12; 95% CI, .03-.21; I2=0%), with no increases in adverse events. There was
      no significant change in walking ability. One trial reported that additional
      physical therapy was likely to be cost-effective in subacute rehabilitation.
      CONCLUSIONS: Additional physical therapy services improve patient activity and
      participation outcomes while reducing hospital length of stay for adults. These
      benefits are likely safe, and there is preliminary evidence to suggest they may
      be cost-effective.

PMID- 29634916
TI  - Revisiting the developmental and cellular role of the pigmentation gene yellow in
      Drosophila using a tagged allele.
AB  - Pigmentation is a diverse and ecologically relevant trait in insects. Pigment
      formation has been studied extensively at the genetic and biochemical levels. The
      temporality of pigment formation during animal development, however, is more
      elusive. Here, we examine this temporality, focusing on yellow, a gene involved
      in the formation of black melanin. We generated a protein-tagged yellow allele in
      the fruit fly Drosophila melanogaster, which allowed us to precisely describe
      Yellow expression pattern at the tissue and cellular levels throughout
      development. We found Yellow expressed in the pupal epidermis in patterns
      prefiguring black pigmentation. We also found Yellow expressed in a few central
      neurons from the second larval instar to adult stages, including a subset of
      neurons adjacent to the clock neurons marked by the gene Pdf. We then
      specifically examined the dynamics of Yellow expression domain and subcellular
      localization in relationship to pigment formation. In particular, we showed how a
      late step of re-internalization is regulated by the large low-density lipoprotein
      receptor-related protein Megalin. Finally we suggest a new function for Yellow in
      the establishment of sharp pigmentation pattern boundaries, whereby this protein
      may assume a structural role, anchoring pigment deposits or pigmentation enzymes
      in the cuticle.

PMID- 29634917
TI  - Ca2+ handling remodeling and STIM1L/Orai1/TRPC1/TRPC4 upregulation in
      monocrotaline-induced right ventricular hypertrophy.
AB  - BACKGROUND: Right ventricular (RV) function is the most important prognostic
      factor for pulmonary arterial hypertension (PAH) patients. The progressive
      increase of pulmonary vascular resistance induces RV hypertrophy (RVH) and at
      term RV failure (RVF). However, the molecular mechanisms of RVH and RVF remain
      understudied. In this study, we gained insights into cytosolic Ca2+ signaling
      remodeling in ventricular cardiomyocytes during the pathogenesis of severe
      pulmonary hypertension (PH) induced in rats by monocrotaline (MCT) exposure, and
      we further identified molecular candidates responsible for this Ca2+ remodeling.
      METHODS AND RESULTS: After PH induction, hypertrophied RV myocytes presented
      longer action potential duration, higher and faster [Ca2+]i transients and
      increased sarcoplasmic reticulum (SR) Ca2+ content, whereas no changes in these
      parameters were detected in left ventricular (LV) myocytes. These modifications
      were associated with increased P-Ser16-phospholamban pentamer expression without
      altering SERCA2a (Sarco/Endoplasmic Reticulum Ca2+-ATPase) pump abundance.
      Moreover, after PH induction, Ca2+ sparks frequency were higher in hypertrophied
      RV cells, while total RyR2 (Ryanodine Receptor) expression and phosphorylation
      were unaffected. Together with cellular hypertrophy, the T-tubules network was
      disorganized. Hypertrophied RV cardiomyocytes from MCT-exposed rats showed
      decreased expression of classical STIM1 (Stromal Interaction molecule) associated
      with increased expression of muscle-specific STIM1 Long isoform, glycosylated
      Orai1 channel form, and TRPC1 and TRPC4 channels, which was correlated with an
      enhanced Ca2+-release-activated Ca2+ (CRAC)-like current. Pharmacological
      inhibition of TRPCs/Orai1 channels in hypertrophied RV cardiomyocytes normalized
      [Ca2+]i transients amplitude, the SR Ca2+ content and cell contractility to
      control levels. Finally, we showed that most of these changes did not appear in
      LV cardiomyocytes. CONCLUSIONS: These new findings demonstrate RV-specific
      cellular Ca2+ cycling remodeling in PH rats with maladaptive RVH and that the
      STIM1L/Orai1/TRPC1/C4-dependent Ca2+ current participates in this Ca2+ remodeling
      in RVH secondary to PH.

PMID- 29634918
TI  - Self-Assembly of alpha-Cyclodextrin and beta-Cyclodextrin: Identification and
      Development of Analytical Techniques.
AB  - Recently, it has been shown that cyclodextrins (CDs) self-assemble in aqueous
      solutions to form aggregates. Such aggregation can give rise to formation of
      particulate matter in aqueous solutions. However, the analytical methodology
      available to detect and quantify these aggregates is still quite inadequate.
      Here, 5 different methods for evaluation of CD aggregate formation and
      determination of the critical aggregation concentration are evaluated: osmometry,
      viscosity, surface tension, dynamic light scattering, and permeability studies.
      Both the viscosity and surface tension methods applied were inadequate for
      aggregate detection, whereas the osmometry method can be used to study CD
      aggregation but with some limitations. Dynamic light scattering has also some
      limitations although it can be applied to detect CD aggregates and to estimate
      their hydrodynamic diameter. Overall, permeation studies proved to be the best
      method to detect and determine critical aggregation concentration. These results
      suggested that beta-cyclodextrin (betaCD) has higher tendency to aggregate than
      alpha-cyclodextrin (alphaCD). Filtration of alphaCD and betaCD solutions affected
      the aggregate size distribution by breaking larger aggregates in to smaller ones
      that then reassembled to regenerate the larger ones upon storage. The osmolality
      studies showed that in aqueous alphaCD and betaCD solutions, solute-solute
      interactions are favored over solute-solvent interactions with consequent CD
      aggregate formation.

PMID- 29634919
TI  - Crystal Structure of Human Dual-Specificity Tyrosine-Regulated Kinase 3 Reveals
      New Structural Features and Insights into its Auto-phosphorylation.
AB  - Dual-specificity tyrosine-regulated kinases (DYRKs) auto-phosphorylate a critical
      tyrosine residue in their activation loop and phosphorylate their substrate on
      serine and threonine residues. The auto-phosphorylation occurs intramolecularly
      and is a one-off event. DYRK3 is selectively expressed at a high level in
      hematopoietic cells and attenuates erythroblast development, leading to anemia.
      In the present study, we determined the crystal structure of the mature form of
      human DYRK3 in complex with harmine, an ATP competitive inhibitor. The crystal
      structure revealed a phosphorylation site, residue S350, whose phosphorylation
      increases the stability of DYRK3 and enhances its kinase activity. In addition,
      our structural and biochemical assays suggest that the N-terminal auto
      phosphorylation accessory domain stabilizes the DYRK3 protein, followed by auto
      phosphorylation of the tyrosine of the activation loop, which is important for
      kinase activity. Finally, our docking analysis provides information for the
      design of novel and potent therapeutics to treat anemia.

PMID- 29634921
TI  - Dynamic changes in ejaculatory bulb size during Drosophila melanogaster aging and
      mating.
AB  - The ejaculatory bulb of Drosophila melanogaster males produces proteins and
      pheromones that play important roles in reproduction. This tissue is also the
      final mixing site for the ejaculate before transfer to the female. The
      ejaculatory bulb's dynamics remain largely unstudied. By microscopy of the
      ejaculatory bulb in maturing adult males, we observed that the ejaculatory bulb
      expands in size as males age. Moreover, we document that when males mate, their
      ejaculatory bulb expands further as ejaculate transfer begins, and then contracts
      halfway through the course of mating as ejaculate transfer finishes. Although
      there is some male-to-male variation in the timing of these changes, ultimately
      the tissue changes in a predictable pattern that gives insight into the active
      mating process in Drosophila.

PMID- 29634922
TI  - Bulimulus tenuissimus (mollusca) as a new potential host of Angiostrogylus
      cantonensis (nematoda), a histological and metabolic study.
AB  - The terrestrial gastropod Bulimulus tenuissimus is widespread in South America.
      It is an intermediate host of many parasites, but there are no records of
      infection of this snail by Angiostrongylus cantonensis, despite the occurrence of
      this parasite and angiostrongyliasis cases in the same areas in which B.
      tenuissimus occurs. For this reason, it is important investigate the
      susceptibility of B. tenuissimus to A. cantonensis-infection, since it can be
      used as intermediate host of A. cantonensis, increasing the list of terrestrial
      gastropods that infect wild and domestic animals and humans with this parasite.
      The purpose of this study was to evaluate the susceptibility of B. tenuissimus to
      experimental infection with L1 larvae of A. cantonensis. The snails were exposed
      to 1200 L1 larvae and it was possible observe many developing larvae in the
      cephalopedal mass and mantle tissues, with intense hemocyte infiltration and
      collagen deposition, but no typical granuloma structures were formed. The glucose
      content and lactate dehydrogenase activity in the hemolymph varied, indicating an
      increase of anaerobic energy metabolism in the middle of infection, but with a
      tendency to return to normal values at the end of pre-patent period. This was
      corroborated by the marked reduction in the glycogen content in the cephalopedal
      mass and digestive gland in the first and second week after exposure, followed by
      a slight increase in the third week. The content of pyruvic acid in the hemolymph
      was 14.84% lower at the end of pre-patent period, and oxalic acid content was
      41.14% higher. These results indicate an aerobic to anaerobic transition process.
      The PAS reaction showed a large amount of glycogen inside the developing larvae
      and muscular tissues of the cephalopedal mass, indicating that despite the high
      consumption of this polysaccharide by the parasite, the snail is able to maintain
      its energy metabolism based on carbohydrates. The results reveal that B.
      tenuissimus is a robust host, which can live with the developing larvae of A.
      cantonensis and overcome the metabolic damages resulting from parasitism.

PMID- 29634920
TI  - Expanding the Paradigm: Intrinsically Disordered Proteins and Allosteric
      Regulation.
AB  - Allosteric regulatory processes are implicated at all levels of biological
      function. Recent advances in our understanding of the diverse and functionally
      significant class of intrinsically disordered proteins have identified a
      multitude of ways in which disordered proteins function within the confines of
      the allosteric paradigm. Allostery within or mediated by intrinsically disordered
      proteins ensures robust and efficient signal integration through mechanisms that
      would be extremely unfavorable or even impossible for globular protein
      interaction partners. Here, we highlight recent examples that indicate the
      breadth of biological outcomes that can be achieved through allosteric regulation
      by intrinsically disordered proteins. Ongoing and future work in this rapidly
      evolving area of research will expand our appreciation of the central role of
      intrinsically disordered proteins in ensuring the fidelity and efficiency of
      cellular regulation.

PMID- 29634923
TI  - Simultaneous exposure of nematophagous fungi, entomopathogenic nematodes and
      entomopathogenic fungi can modulate belowground insect pest control.
AB  - Entomopathogenic nematodes (EPNs) and fungi (EPF) are well known biological
      control agents (BCAs) against insect pests. Similarly, the nematophagous fungi
      (NF) are considered good BCA candidates for controlling plant parasitic
      nematodes. Because NF can employ EPNs as food and interact with EPF, we speculate
      that the simultaneous application of EPNs and EPF might result in higher insect
      mortality, whereas the triple species combination with NF will reduce the EPN and
      EPF activity by predation or inhibition. Here we evaluated single, dual (EPN +
      EPF, EPF + NF, EPN + NF) and triple (EPN + EPF + NF) combinations of one EPN,
      Steinernema feltiae (Rhabditida: Steinernematidae), one EPF, Beauveria bassiana
      (Hypocreales: Clavicipitaceae), and two NF, Arthrobotrys musiformis (Orbiliales:
      Orbiliaceae) and Purpureocillium lilacinum (Hypocreales: Ophiocordycipitaceae)
      under laboratory conditions. First, we showed that EPF reduced the growth rate of
      NF and vice versa when combined in both rich and limiting media, suggesting a
      negative interaction when combining both fungi. Three different fungal
      applications (contact with mycelia-conidia, immersion in conidial suspension, and
      injection of conidial suspension) were tested in single, dual and triple species
      combinations, evaluating Galleria mellonella (Lepidoptera: Pyralidae) larval
      mortality and time to kill. When mycelia was presented, the EPF appeared to be
      the dominant in combined treatments, whereas in immersion exposure was the EPN.
      In both types of exposure, NF alone did not produce any effect on larvae.
      However, when A. musiformis was injected, it produced larval mortalities >70% in
      the same time span as EPN. Overall, additive effects dominated the dual and
      triple combinations, with the exception of injection method, where synergisms
      occurred for both NF species combined with EPN + EPF. This study illustrates how
      differences in species combination and timing of fungal arrival can modulate the
      action of BCAs when augmented in the soil. Further studies are required to fine
      tune these multitrophic interactions to provide successful, sustainable and
      resilient pest management in agroecosystems.

PMID- 29634924
TI  - Loss of nucleolar localization of NAT10 promotes cell migration and invasion in
      hepatocellular carcinoma.
AB  - NAT10, a nucleolar acetyltransferase, participates in a variety of cellular
      processes including ribosome biogenesis and DNA damage response.
      Immunohistochemistry staining showed that cytoplasmic and membranous NAT10 is
      related to the clinical pathologic characteristics in human cancer tissues.
      However, the mechanism about how NAT10 translocates from the nucleolus to
      cytoplasm and membrane is unclear. Here, we obtain a NAT10 deletion mutant
      localizing in cytoplasm and membrane. Bioinformatics analysis showed that
      residues 68-75 and 989-1018 are two potential nuclear localization signals (NLS)
      of NAT10. GFP-NAT10 deletion mutant (Delta989-1018) predominantly translocates
      into cytoplasm with faint signal retained in the nucleolus, while GFP
      NAT10(Delta68-75) still remains in the nucleolus and nucleoplasm, indicating
      residues 989-1018 is the main nucleolar localization signal (NuLS). GFP-NAT10-D3,
      with both fragments (residues 68-75 and 989-1018) deleted, completely excludes
      from the nucleolus and translocates to cytoplasm and membrane. Therefore,
      complete NuLSs of NAT10 should include residues 68-75 and 989-1018. The
      cytoplasmic and membranous NAT10 mutant (Flag-NAT10-D3) colocalizes with alpha
      tubulin in cytoplasm and with integrin on cell membrane. Importantly, Flag-NAT10
      D3 promotes alpha-tubulin acetylation and stabilizes microtubules. Consequently,
      Flag-NAT10-D3 promotes migration and invasion in hepatocellular carcinoma (HCC)
      cells. Statistical analysis of immunohistochemistry staining of NAT10 in HCC
      tissues demonstrates that the cytoplasmic NAT10 is correlated with poorer
      prognosis compared with nuclear NAT10, while the membranous NAT10 predicts the
      poorest clinical outcome of the patients. We thus provide the evidence for the
      function of cytoplasmic and membranous NAT10 in the metastasis and prognosis of
      HCC patients.

PMID- 29634925
TI  - Myeloid sirtuin1 deficiency aggravates hippocampal inflammation in mice fed high
      fat diets.
AB  - Chronic low-grade inflammation-induced insulin resistance is associated with
      neuroinflammation. Myeloid sirtuin1 (SIRT1) deficiency aggravates high-fat diet
      (HFD)-induced insulin resistance. However, the function of myeloid-specific SIRT1
      in the hippocampus of obese mice is largely unknown. To address this question, we
      fed myeloid SIRT1 knockout (KO) mice a HFD for 40 weeks. We found that HFD-fed
      SIRT1 KO mice had increased insulin resistance and macrophage infiltration in
      adipose tissue than wild type (WT) mice. Levels of HFD-induced lipocalin-2 (LCN2)
      were lower in SIRT1 KO mice than in WT. HFD-induced hippocampal LCN2 expression
      was lower in HFD-fed SIRT1 KO mice than in WT. Hippocampal acetylation of nuclear
      factor-kappaB (NF-kappaB) and amyloid precursor protein levels were higher in HFD
      fed SIRT1 KO mice than in HFD-fed WT mice. Taken together, our results suggest
      that targeted induction of the anti-inflammatory effects of SIRT1 and LCN2 may
      help prevent obesity-associated insulin resistance and neuroinflammation.

PMID- 29634926
TI  - Astrocytes synthesize primary and cyclopentenone prostaglandins that are negative
      regulators of their proliferation.
AB  - Recently, the modulation of cellular inflammatory responses via endogenous
      regulators became a major focus of medically relevant investigations.
      Prostaglandins (PGs) are attractive regulatory molecules, but their synthesis and
      mechanisms of action in brain cells are still unclear. Astrocytes are involved in
      manifestation of neuropathology and their proliferation is an important part of
      astrogliosis, a cellular neuroinflammatory response. The aims of our study were
      to measure synthesis of PGs by astrocytes, and evaluate their influence on
      proliferation in combination with addition of inflammatory pathway inhibitors.
      With UPLC-MS/MS analysis we detected primary PGs (1410 +/- 36 pg/mg PGE2, 344 +/-
      24 PGD2) and cyclopentenone PGs (cyPGs) (87 +/- 17 15d-PGJ2, 308 +/- 23 PGA2) in
      the extracellular medium after 24-h lipopolysaccharide (LPS) stimulation of
      astrocytes. PGs reduced astrocytic proliferation with the following order of
      potencies (measured as inhibition at 20 MUM): most potent 15d-PGJ2 (90%) and PGA2
      (80%), > PGD2 (40%) > 15d-PGA2 (20%) > PGE2 (5%), the least potent. However,
      PGF2alpha and 2-cyclopenten-1-one, and ciglitazone and rosiglitazone (synthetic
      agonists of PPARgamma) had no effect. Combinations of cyPGs with SC-560 or NS-398
      (specific anti-inflammatory inhibitors of cyclooxygenase-1 and -2, respectively)
      were not effective; while GW9662 (PPARgamma antagonist) or MK-741 (inhibitor of
      multidrug resistance protein-1, MRP1, and CysLT1 receptors) amplified the
      inhibitory effect of PGA2 and 15d-PGJ2. Although concentrations of individual PGs
      and cyPGs are low, all of them, as well as primary PGs suppress proliferation.
      Thus, the effects are potentially additive, and activated PGs synthesis
      suppresses proliferation in astrocytes.

PMID- 29634927
TI  - The chemorepellent draxin is involved in hippocampal mossy fiber projection.
AB  - Lamina-specific afferent innervation of the mammalian hippocampus is critical for
      its function. We investigated the relevance of the chemorepellent draxin to the
      laminar projections of three principal hippocampal afferents: mossy fibers,
      entorhinal, and associational/commissural fibers. We observed that draxin
      deficiency led to abnormal projection of mossy fibers but not other afferents.
      Immunohistochemical analysis indicated that draxin is expressed in the dentate
      gyrus and cornu ammonis (CA) 3 at postnatal day 0, when dentate granule cells
      begin to extend mossy fibers towards CA3. Furthermore, a neurite growth assay
      using dissociated cells of the neonatal dentate gyrus revealed that draxin
      inhibited the growth of calbindin-D28k-expressing mossy fibers in vitro. Taken
      together, we conclude that draxin is a key molecule in the regulation of mossy
      fiber projections.

PMID- 29634928
TI  - Down-regulation of FOXR2 inhibits non-small cell lung cancer cell proliferation
      and invasion through the Wnt/beta-catenin signaling pathway.
AB  - Forkhead box R2 (FOXR2), a new member of the FOX family, is an important player
      in a wide range of cellular processes such as proliferation, migration,
      differentiation and apoptosis. Recently, FOXR2 has been reported to be implicated
      in cancer development. However, the biological functions of FOXR2 in non-small
      cell lung cancer (NSCLC) remain unclear. In this study, we investigated the
      specific role of FOXR2 in NSCLC. The results showed that down-regulation of FOXR2
      significantly inhibited NSCLC cell proliferation and invasion in vitro and
      suppressed NSCLC cell growth and metastasis in vivo. In addition, the decrease in
      FOXR2 expression markedly reduced the protein levels of beta-catenin, cyclinD1
      and c-Myc and hence inactivated the Wnt/beta-catenin pathway in NSCLC cells.
      Taken together, we concluded that FOXR2 might be considered as a promising
      therapeutic target for NSCLC treatment.

PMID- 29634929
TI  - Structural insights into the backbone-circularized granulocyte colony-stimulating
      factor containing a short connector.
AB  - Backbone circularization is a powerful approach for enhancing the structural
      stability of polypeptides. Herein, we present the crystal structure of the
      circularized variant of the granulocyte colony-stimulating factor (G-CSF) in
      which the terminal helical region was circularized using a short, two-amino acid
      connector. The structure revealed that the N- and C-termini were indeed connected
      by a peptide bond. The local structure of the C-terminal region transited from an
      alpha helix to 310 helix with a bend close to the N-terminal region, indicating
      that the structural change offset the insufficient length of the connector. This
      is the first-ever report of a crystal structure of the backbone of a circularized
      protein. It will facilitate the development of backbone circularization
      methodology.

PMID- 29634930
TI  - HCMV Assembly Is Totally Tubular.
AB  - Microtubules are normally organized at centrosomes, but other sites can also
      serve as microtubule organizing centers (MTOCs). In this issue of Developmental
      Cell, Procter et al. (2018) show that the human cytomegalovirus virion assembly
      compartment acts as a dynamic Golgi-derived MTOC where EB3 nucleates microtubules
      and regulates infectious virion production.

PMID- 29634931
TI  - Neurovascular Communication during CNS Development.
AB  - A precise communication between the nervous and the vascular systems is crucial
      for proper formation and function of the central nervous system (CNS).
      Interestingly, this communication does not only occur by neural cells regulating
      the growth and properties of the vasculature, but new studies show that blood
      vessels actively control different neurodevelopmental processes. Here, we review
      the current knowledge on how neurons in particular influence growing blood
      vessels during CNS development and on how vessels participate in shaping the
      neural compartment. We also review the identified molecular mechanisms of this
      bidirectional communication.

PMID- 29634934
TI  - Metastasis of Circulating Tumor Cells: Speed Matters.
AB  - The mechanisms involved in tumor cell extravasation during metastasis remain
      incompletely understood. In this issue of Developmental Cell, Follain and
      colleagues (2018) demonstrate that blood flow velocity is an important regulator
      of circulating tumor cell exit from the bloodstream.

PMID- 29634933
TI  - The Role of Mitotic Cell-Substrate Adhesion Re-modeling in Animal Cell Division.
AB  - Animal cells undergo a dramatic series of shape changes as they divide, which
      depend on re-modeling of cell-substrate adhesions. Here, we show that while focal
      adhesion complexes are disassembled during mitotic rounding, integrins remain in
      place. These integrin-rich contacts connect mitotic cells to the underlying
      substrate throughout mitosis, guide polarized cell migration following mitotic
      exit, and are functionally important, since adherent cells undergo division
      failure when removed from the substrate. Further, the ability of cells to re
      spread along pre-existing adhesive contacts is essential for division in cells
      compromised in their ability to construct a RhoGEF-dependent (Ect2) actomyosin
      ring. As a result, following Ect2 depletion, cells fail to divide on small
      adhesive islands but successfully divide on larger patterns, as the connection
      between daughter cells narrows and severs as they migrate away from one another.
      In this way, regulated re-modeling of cell-substrate adhesions during mitotic
      rounding aids division in animal cells.

PMID- 29634932
TI  - The RAB11A-Positive Compartment Is a Primary Platform for Autophagosome Assembly
      Mediated by WIPI2 Recognition of PI3P-RAB11A.
AB  - Autophagy is a critical pathway that degrades intracytoplasmic contents by
      engulfing them in double-membraned autophagosomes that are conjugated with LC3
      family members. These membranes are specified by phosphatidylinositol 3-phosphate
      (PI3P), which recruits WIPI2, which, in turn, recruits ATG16L1 to specify the
      sites of LC3-conjugation. Conventionally, phosphatidylinositides act in concert
      with other proteins in targeting effectors to specific membranes. Here we
      describe that WIPI2 localizes to autophagic precursor membranes by binding
      RAB11A, a protein that specifies recycling endosomes, and that PI3P is formed on
      RAB11A-positive membranes upon starvation. Loss of RAB11A impairs the recruitment
      and assembly of the autophagic machinery. RAB11A-positive membranes are a primary
      direct platform for canonical autophagosome formation that enables autophagy of
      the transferrin receptor and damaged mitochondria. While this compartment may
      receive membrane inputs from other sources to enable autophagosome biogenesis,
      RAB11A-positive membranes appear to be a compartment from which autophagosomes
      evolve.

PMID- 29634936
TI  - Mitosis-Resistant Adhesions Provide Molecular Memory to Dividing Cells.
AB  - During mitosis, animal cells disassemble focal adhesions and round up while
      remaining attached to the substrata via actin cables and unknown adhesive
      structures. In this issue of Developmental Cell, Dix et al. (2018) describe
      integrin-positive adhesions, devoid of classical focal adhesion components, that
      persist throughout mitosis to contribute to re-spreading.

PMID- 29634935
TI  - Hemodynamic Forces Tune the Arrest, Adhesion, and Extravasation of Circulating
      Tumor Cells.
AB  - Metastatic seeding is driven by cell-intrinsic and environmental cues, yet the
      contribution of biomechanics is poorly known. We aim to elucidate the impact of
      blood flow on the arrest and the extravasation of circulating tumor cells (CTCs)
      in vivo. Using the zebrafish embryo, we show that arrest of CTCs occurs in
      vessels with favorable flow profiles where flow forces control the adhesion
      efficacy of CTCs to the endothelium. We biophysically identified the threshold
      values of flow and adhesion forces allowing successful arrest of CTCs. In
      addition, flow forces fine-tune tumor cell extravasation by impairing the
      remodeling properties of the endothelium. Importantly, we also observe
      endothelial remodeling at arrest sites of CTCs in mouse brain capillaries.
      Finally, we observed that human supratentorial brain metastases preferably
      develop in areas with low perfusion. These results demonstrate that hemodynamic
      profiles at metastatic sites regulate key steps of extravasation preceding
      metastatic outgrowth.

PMID- 29634938
TI  - A Tale of Two Cycles.
AB  - Two of the fundamental rhythms of eukaryotic life are the circadian clock and the
      cell division cycle. In this issue of Developmental Cell, Fung-Uceda and
      colleagues (2018) have elucidated a molecular mechanism linking the circadian
      clock to the cell cycle in the plant Arabidopsis thaliana.

PMID- 29634940
TI  - Metastatic Renal Cell Carcinoma Presenting as a Solitary Gastric Polyp.

PMID- 29634941
TI  - Mechanistic Insights into Transmissible Cancers of Mammals.
AB  - Transmissible cancers are clonal lineages that spread through populations via
      contagious cancer cells. In this issue of Cancer Cell, two articles by Stammnitz
      et al. and Frampton et al. present novel insights into the potential mechanisms
      underlying the propagation of naturally occurring transmissible cancers in
      mammals.

PMID- 29634939
TI  - The HCMV Assembly Compartment Is a Dynamic Golgi-Derived MTOC that Controls
      Nuclear Rotation and Virus Spread.
AB  - Human cytomegalovirus (HCMV), a leading cause of congenital birth defects, forms
      an unusual cytoplasmic virion maturation site termed the "assembly compartment"
      (AC). Here, we show that the AC also acts as a microtubule-organizing center
      (MTOC) wherein centrosome activity is suppressed and Golgi-based microtubule (MT)
      nucleation is enhanced. This involved viral manipulation of discrete functions of
      MT plus-end-binding (EB) proteins. In particular, EB3, but not EB1 or EB2, was
      recruited to the AC and was required to nucleate MTs that were rapidly
      acetylated. EB3-regulated acetylated MTs were necessary for nuclear rotation
      prior to cell migration, maintenance of AC structure, and optimal virus
      replication. Independently, a myristoylated peptide that blocked EB3-mediated
      enrichment of MT regulatory proteins at Golgi regions of the AC also suppressed
      acetylated MT formation, nuclear rotation, and infection. Thus, HCMV offers new
      insights into the regulation and functions of Golgi-derived MTs and the
      therapeutic potential of targeting EB3.

PMID- 29634937
TI  - Coordination of Receptor Tyrosine Kinase Signaling and Interfacial Tension
      Dynamics Drives Radial Intercalation and Tube Elongation.
AB  - We sought to understand how cells collectively elongate epithelial tubes. We
      first used 3D culture and biosensor imaging to demonstrate that epithelial cells
      enrich Ras activity, phosphatidylinositol (3,4,5)-trisphosphate (PIP3), and F
      actin to their leading edges during migration within tissues. PIP3 enrichment
      coincided with, and could enrich despite inhibition of, F-actin dynamics,
      revealing a conserved migratory logic compared with single cells. We discovered
      that migratory cells can intercalate into the basal tissue surface and contribute
      to tube elongation. We then connected molecular activities to subcellular
      mechanics using force inference analysis. Migration and transient intercalation
      required specific and similar anterior-posterior ratios of interfacial tension.
      Permanent intercalations were distinguished by their capture at the boundary
      through time-varying tension dynamics. Finally, we integrated our experimental
      and computational data to generate a finite element model of tube elongation. Our
      model revealed that intercalation, interfacial tension dynamics, and high basal
      stress are together sufficient for mammary morphogenesis.

PMID- 29634942
TI  - More Rules, Still Exceptions: Understanding Immunomodulatory Antibody Activity In
      Vivo.
AB  - Understanding how agonistic and checkpoint control antibodies mediate their
      activity in vivo is essential for further development of these promising anti
      cancer therapies. In this issue of Cancer Cell, studies by Vargas et al. and Yu
      et al. provide insights into the mode of action of CTLA-4- and CD40-specific
      antibodies.

PMID- 29634943
TI  - T Cell Dysfunction in Cancer.
AB  - Therapeutic reinvigoration of tumor-specific T cells has greatly improved
      clinical outcome in cancer. Nevertheless, many patients still do not achieve
      durable benefit. Recent evidence from studies in murine and human cancer suggest
      that intratumoral T cells display a broad spectrum of (dys-)functional states,
      shaped by the multifaceted suppressive signals that occur within the tumor
      microenvironment. Here we discuss the current understanding of T cell dysfunction
      in cancer, the value of novel technologies to dissect such dysfunction at the
      single cell level, and how our emerging understanding of T cell dysfunction may
      be utilized to develop personalized strategies to restore antitumor immunity.

PMID- 29634944
TI  - The Immune Revolution: A Case for Priming, Not Checkpoint.
AB  - Most tumors are unresponsive to immune checkpoint blockade, especially if deep
      immunosuppression in the tumor develops prior to and prevents T cell
      immunosurveillance. Failed or frustrated T cell priming often needs repair before
      successful sensitization to PD-1/PD-L1 blockade. CD40 activation plays a critical
      role in generating T cell immunity, by activating dendritic cells, and converting
      cold tumors to hot. In preclinical studies, agonistic CD40 antibodies demonstrate
      T cell-dependent anti-tumor activity, especially in combination with
      chemotherapy, checkpoint inhibitory antibodies, and other immune modulators. With
      the advent of multiple CD40 agonists with acceptable single-agent toxicity,
      clinical evaluation of CD40 combinations has accelerated.

PMID- 29634945
TI  - The Influence of the Gut Microbiome on Cancer, Immunity, and Cancer
      Immunotherapy.
AB  - The microbiome is receiving significant attention given its influence on a host
      of human diseases including cancer. Its role in response to cancer treatment is
      becoming increasingly apparent, with evidence suggesting that modulating the gut
      microbiome may affect responses to numerous forms of cancer therapy. A working
      knowledge of the microbiome is vital as we move forward in this age of precision
      medicine, and an understanding of the microbiome's influence on immune responses
      and cancer is key. It is also important to understand factors influencing the gut
      microbiome and strategies to manipulate the microbiome to augment therapeutic
      responses.

PMID- 29634947
TI  - Oncolytic Viruses as Antigen-Agnostic Cancer Vaccines.
AB  - Selective destruction of neoplastic tissues by oncolytic viruses (OVs) leads to
      antigen-agnostic boosting of neoantigen-specific cytotoxic T lymphocyte (CTL)
      responses, making OVs ideal companions for checkpoint blockade therapy. Here we
      discuss the mechanisms whereby OVs modulate both adjuvanticity and antigenicity
      of tumor cells. Suppression of antitumor immunity after OV therapy has not been
      observed, possibly because viral antigen expression diminishes as the antiviral
      response matures, thereby progressively honing the CTL response to tumor
      neoantigens. By combining direct in situ tumor destruction with the ability to
      boost antitumor immunity, OVs also have the potential to be powerful standalone
      cancer therapies.

PMID- 29634946
TI  - Emerging Concepts for Immune Checkpoint Blockade-Based Combination Therapies.
AB  - Checkpoint blockade has formally demonstrated that reactivating anti-tumor immune
      responses can regress tumors. However, this only occurs in a fraction of
      patients. Incorporating these therapies in more powerful combinations is thus a
      logical next step. Here, we review functional roles of immune checkpoints and
      molecular determinants of checkpoint-blockade clinical activity. Limited-size T
      cell-infiltrated tumors, differing substantially from "self," generally respond
      to checkpoint blockade. Therefore, we propose that reducing tumor burden and
      increasing tumor immunogenicity are key factors to improve immunotherapy. Lastly,
      we outline criteria to select proper immunotherapy combination partners and
      highlight the importance of activity biomarkers for timely treatment
      optimization.

PMID- 29634948
TI  - The Origins and Vulnerabilities of Two Transmissible Cancers in Tasmanian Devils.
AB  - Transmissible cancers are clonal lineages that spread through populations via
      contagious cancer cells. Although rare in nature, two facial tumor clones affect
      Tasmanian devils. Here we perform comparative genetic and functional
      characterization of these lineages. The two cancers have similar patterns of
      mutation and show no evidence of exposure to exogenous mutagens or viruses. Genes
      encoding PDGF receptors have copy number gains and are present on
      extrachromosomal double minutes. Drug screening indicates causative roles for
      receptor tyrosine kinases and sensitivity to inhibitors of DNA repair. Y
      chromosome loss from a male clone infecting a female host suggests immunoediting.
      These results imply that Tasmanian devils may have inherent susceptibility to
      transmissible cancers and present a suite of therapeutic compounds for use in
      conservation.

PMID- 29634949
TI  - Molecular Signatures of Regression of the Canine Transmissible Venereal Tumor.
AB  - The canine transmissible venereal tumor (CTVT) is a clonally transmissible cancer
      that regresses spontaneously or after treatment with vincristine, but we know
      little about the regression mechanisms. We performed global transcriptional,
      methylation, and functional pathway analyses on serial biopsies of vincristine
      treated CTVTs and found that regression occurs in sequential steps; activation of
      the innate immune system and host epithelial tissue remodeling followed by immune
      infiltration of the tumor, arrest in the cell cycle, and repair of tissue damage.
      We identified CCL5 as a possible driver of CTVT regression. Changes in gene
      expression are associated with methylation changes at specific intragenic sites.
      Our results underscore the critical role of host innate immunity in triggering
      cancer regression.

PMID- 29634950
TI  - Adipocyte p62/SQSTM1 Suppresses Tumorigenesis through Opposite Regulations of
      Metabolism in Adipose Tissue and Tumor.
AB  - Obesity is a leading risk factor for cancer. However, understanding the crosstalk
      between adipocytes and tumor cells in vivo, independently of dietary
      contributions, is a major gap in the field. Here we used a prostate cancer (PCa)
      mouse model in which the signaling adaptor p62/Sqstm1 is selectively inactivated
      in adipocytes. p62 loss in adipocytes results in increased osteopontin secretion,
      which mediates tumor fatty acid oxidation and invasion, leading to aggressive
      metastatic PCa in vivo. Furthermore, p62 deficiency triggers in adipocytes a
      general shutdown of energy-utilizing pathways through mTORC1 inhibition, which
      supports nutrient availability for cancer cells. This reveals a central role of
      adipocyte's p62 in the symbiotic adipose tissue-tumor collaboration that enables
      cancer metabolic fitness.

PMID- 29634951
TI  - Targeting the Senescence-Overriding Cooperative Activity of Structurally
      Unrelated H3K9 Demethylases in Melanoma.

PMID- 29634952
TI  - Dual Targeting of Oncogenic Activation and Inflammatory Signaling Increases
      Therapeutic Efficacy in Myeloproliferative Neoplasms.

PMID- 29634953
TI  - Circular RNA expression profiles of mouse ovaries during postnatal development
      and the function of circular RNA epidermal growth factor receptor in granulosa
      cells.
AB  - PURPOSE: Circular RNAs (circRNAs) are a class of noncoding RNAs that can regulate
      gene expression at the post-transcriptional level. The contribution of circRNAs
      in the regulation of granulosa cells (GCs) functions is not yet clear. The aim of
      this study was to analyze circRNA expression in adult and neonate ovaries,
      uncover the biological roles of circ_0002861 (circEGFR) and identify the
      mechanism by which it modulates follicular development. BASIC PROCEDURES: The
      circRNA expression profiles of adult and neonatal mouse ovaries were explored by
      high-throughput sequencing. The function of circEGFR was measured by RNA
      fluorescence in situ hybridization, overexpression, knockdown, RNA
      immunoprecipitation and luciferase reporter assays in GCs. MAIN FINDINGS:
      Numerous differentially expressed circRNAs were identified in adult and neonatal
      ovaries. Through circRNAs expression patterns and Kyoto Encyclopedia of Genes and
      Genomes (KEGG) pathway analysis, estrogen signaling was found to be upregulated
      in adult ovaries compared with neonate ovaries. Further analysis revealed that
      the expression of circEGFR (circ_0002861, ID: mmu_circ_0002861 in circBase) was
      increased in adult ovaries compared with neonate ovaries. circEGFR is formed by
      splicing from exons 14 and 15 of the epidermal growth factor receptor (EGFR) gene
      to produce a covalently linked 249-nucleotide circRNA. Overexpression of circEGFR
      increased estradiol (E2) production and GCs growth, whereas circEGFR knockdown
      enhanced progesterone production and inhibited (E2) secretion by GCs.
      Bioinformatic screening identified several binding sites for miR-125a-3p in the
      circEGFR sequence. RNA immunoprecipitation and luciferase reporter assays
      demonstrated that circEGFR may act as a sponge for miR-125a-3p, thus modulating
      Fyn expression. PRINCIPAL CONCLUSIONS: These findings illustrate that circEGFR
      may play a vital role in ovarian GCs by modulating Fyn via competitive binding
      with miR-125a-3p. Our results suggest potential applications of circEGFR in
      reproductive and steroid-related disorder therapy.

PMID- 29634954
TI  - Advances at the intersection of sleep and metabolism research.

PMID- 29634955
TI  - Hazard assessment of three haloacetic acids, as byproducts of water disinfection,
      in human urothelial cells.
AB  - Disinfection by-products (DBPs) are compounds produced in the raw water
      disinfection processes. Although increased cancer incidence has been associated
      with exposure to this complex mixture, the carcinogenic potential of individual
      DBPs remains not well known; thus, further studies are required. Haloacetic acids
      (HAAs) constitute an important group among DBPs. In this study, we have assessed
      the in vitro carcinogenic potential of three HAAs namely chloro-, bromo-, and
      iodoacetic acids. Using a long-term (8 weeks) and sub-toxic doses exposure
      scenario, different in vitro transformation markers were evaluated using a human
      urothelial cell line (T24). Our results indicate that long-term exposure to low
      doses of HAAs did not reproduce the genotoxic effects observed in acute
      treatments, where oxidative DNA damage was induced. No changes in the
      transformation endpoints analyzed were observed, as implied by the absence of
      significant morphological, cell growth rate and anchorage-independent cell growth
      pattern modifications. Interestingly, HAA-long-term exposed cells developed
      resistance to oxidative stress damage, what would explain the observed
      differences between acute and long-term exposure conditions. Accordingly, data
      obtained under long-term exposure to sub-toxic doses of HAAs could be more
      accurate, in terms of risk assessment, than under acute exposure scenarios.

PMID- 29634956
TI  - Accelerated evolution of toxin genes: Exonization and intronization in snake
      venom disintegrin/metalloprotease genes.
AB  - Toxin genes in animals undergo accelerated evolution compared to non-toxin genes
      to be effective and competitive in prey capture, as well as to enhance their
      predator defense. Several mechanisms have been proposed to explain this unusual
      phenomenon. These include (a) frequent mutations in exons compared to introns and
      nonsynonymous substitutions in exons; (b) high frequency of point mutations are
      due to the presence of more unstable triplets in exons compared to introns; (c)
      Accelerated Segment Switch in Exons to alter Targeting (ASSET); (d) Rapid
      Accumulation of Variations in Exposed Residues (RAVERs); (e) alteration in intron
      exon boundary; (f) deletion of exon; and (g) loss/gain of domains through
      recombination. By systematic analyses of snake venom disintegrin/metalloprotease
      genes, I describe a new mechanism in the evolution of these genes through
      exonization and intronization. In the evolution of RTS/KTS disintegrins, a new
      exon (10a) is formed in intron 10 of the disintegrin/metalloprotease gene. Unlike
      more than 90% new exons that are from repetitive elements in introns, exon 10a
      originated from a non-repetitive element. To incorporate exon 10a, part of the
      exon 11 is intronized to retain the open reading frame. This is the first case of
      simultaneous exonization and intronization within a single gene. This new
      mechanism alters the function of toxins through drastic changes to the molecular
      surface via insertion of new exons and deletion of exons.

PMID- 29634957
TI  - The effect of repeated bouts of hyperaemia on sensory nerve-mediated cutaneous
      vasodilatation in humans.
AB  - PURPOSE: To investigate cutaneous sensory nerve contribution to hyperaemia
      following chronic shear stress training. METHODS: Eleven males underwent a shear
      stress intervention (forearm occlusion 5 s, rest 10 s) for 30 min, 5 times.week-1
      for 6 weeks on one arm, the other was an untreated control. Skin blood flow was
      measured using laser-Doppler flowmetry, and sensory nerve function was assessed
      with and without blockade with EMLA cream in response to 3 levels of local
      heating (39, 42, and 44  degrees C) and post-occlusive reactive hyperaemia
      (PORH). RESULTS: In response to local heating, EMLA treatment significantly
      delayed the onset of vasodilatation (p < 0.001), time-to-peak (p < 0.001), time
      to 39  degrees C (p < 0.02), time to 42  degrees C (p < 0.006), but not time to
      44  degrees C (p > 0.2). EMLA treatment also increased time-to-peak for PORH (p
      <= 0.01). In the experimental limb after 6 weeks, both onset time and time to
      peak were shorter in response to local heating at the untreated and EMLA-treated
      sites (all p < 0.001). There were no changes in time-to-peak for PORH at the
      untreated and EMLA-treated sites (p >= 0.4); however, the peak PORH response was
      reduced with EMLA treatment (p <= 0.03). The 6-week intervention increased the
      peak PORH at the untreated sites (p < 0.001) but not at EMLA-treated (p > 0.05)
      sites. Comparing the control limb before and after 6 weeks, no differences in
      responses occurred at either the untreated skin sites (p >= 0.9) or the EMLA
      treated sites (p >= 0.9). CONCLUSIONS: Sensory nerve blockade attenuated the
      improvements in cutaneous vascular responses to thermal hyperaemia and PORH
      following chronic exposure to shear stress. These data demonstrate an important
      role for sensory nerve function in the initiation of vasodilatation to both PORH
      and thermal hyperaemia, in both the time to onset and the magnitude of
      vasodilatation.

PMID- 29634959
TI  - Mechanical differences between ATP and ADP actin states: A molecular dynamics
      study.
AB  - This paper aims to give a comprehensive atomistic modeling of the nanomechanical
      behavior of actin monomer. Actin is a ubiquitous and essential component of
      cytoskeleton which forms many different cellular structures. Despite for several
      years great effort has been devoted to the investigation of mechanical properties
      of the actin filament, studies on the nanomechanical behavior of actin monomer
      are still lacking. These scales are, however, important for a complete
      understanding of the role of actin as an important component in the cytoskeleton
      structure. Based on the accuracy of atomistic modeling methods such as molecular
      dynamics simulations, steered molecular dynamics method is performed to assess
      tension of monomeric G-actin molecule under different types of mechanical loading
      including axial and lateral. As a result, stress-strain curves are obtained in
      aqueous solution, with either ATP or ADP bound in the nucleotide binding pocket.
      The obtained results yield evaluation of the tensile stiffness of a single actin
      monomer in lateral and normal direction. In order to compare the behavior of ATP
      and ADP G-actins, the number of hydrogen bonds and nonbonded interactions between
      the nucleotide and the protein are analyzed. Moreover, The effect of virtual
      spring of steered molecular dynamics on the mechanical behavior of actin monomer
      is investigated. The results reveal increasing the virtual spring constant leads
      to convergence of the stiffness. Moreover, in this paper, a generalized model is
      proposed to extend the obtained results for the monomeric G-actin scale to the
      actin filament. Our modeling estimated a persistence length of actin filament
      15.41 um, close to experimental measurements. Moreover, In this paper, the
      breaking force actin-actin bond is evaluated using steered molecular dynamics
      simulation. By applying a tensile force, actin-actin bond ruptured at 4197.5 pN.

PMID- 29634958
TI  - Anticoagulation Beyond 3 to 6Months: What Does the Data Tell Us?
AB  - Patients with a history of deep vein thrombosis and pulmonary embolism are at
      risk for a recurrent event. This is particularly true of patients with idiopathic
      events or events related to low risk triggers. In these patients extending
      anticoagulation beyond 3 to 6months may be warranted. Using clinical risk,
      biomarker analysis and risk stratification protocols we can make the best
      recommendations to patients with respect to the risks and benefits of ongoing
      therapy. Trials demonstrating benefit from low-dose aspirin for secondary
      prophylaxis may provide an option for patients in whom ongoing anticoagulation is
      deemed unsafe. In addition, recent introduction of the direct oral anticoagulants
      have expanded options for secondary prophylaxis for preventing venous
      thromboembolism recurrence.

PMID- 29634960
TI  - A PDE multiscale model of hepatitis C virus infection can be transformed to a
      system of ODEs.
AB  - Direct-acting antivirals (DAAs) treat hepatitis C virus (HCV) by targeting its
      intracellular viral replication. DAAs are effective and deliver high clinical
      performance against HCV infection, but optimization of the DAA treatment regimen
      is ongoing. Different classes of DAAs are currently under development, and HCV
      treatments that combine two or three DAAs with different action mechanisms are
      being improved. To accurately quantify the antiviral effect of these DAA
      treatments and optimize multi-drug combinations, we must describe the
      intracellular viral replication processes corresponding to the action mechanisms
      by multiscale mathematical models. Previous multiscale models of HCV treatment
      have been formulated by partial differential equations (PDEs). However,
      estimating the parameters from clinical datasets requires comprehensive numerical
      PDE computations that are time consuming and often converge poorly. Here, we
      propose a user-friendly approach that transforms a standard PDE multiscale model
      of HCV infection (Guedj J et al., Proc. Natl. Acad. Sci. USA 2013; 110(10):3991
      6) to mathematically identical ordinary differential equations (ODEs) without any
      assumptions. We also confirm consistency between the numerical solutions of our
      transformed ODE model and the original PDE model. This relationship between a
      detailed structured model and a simple model is called ''model aggregation
      problem'' and a fundamental important in theoretical biology. In particular, as
      the parameters of ODEs can be estimated by already established methods, our
      transformed ODE model and its modified version avoid the time-consuming
      computations and are broadly available for further data analysis.

PMID- 29634961
TI  - Silent pauses in aphasia.
AB  - Pauses may be studied as an aspect of the temporal organization of speech, as
      well as an index of internal cognitive processes, such as word access, selection
      and retrieval, monitoring, articulatory planning, and memory. Several studies
      have demonstrated specific distributional patterns of pauses in typical speech.
      However, evidence from patients with language impairment is sparse and restricted
      to small-scale studies. The aim of the present study is to investigate empty
      pause distribution and associations between pause variables and linguistic
      elements in aphasia. Eighteen patients with chronic aphasia following a left
      hemisphere stroke were recruited. The control group consisted of 19 healthy
      adults matched for age, gender, and years of formal schooling. Speech samples
      from both groups were transcribed, and silent pauses were annotated using ELAN.
      Our results indicate that in both groups, pause duration distribution follows a
      log-normal bimodal model with significantly different thresholds between the two
      populations, yet specific enough for each distribution to justify classification
      into two distinct groups of pauses for each population: short and long. Moreover,
      we found differences between the patient and control group, prominently with
      regard to long pause duration and rate. Long pause indices were also associated
      with fundamental linguistics elements, such as mean length of utterance. Overall,
      we argue that post-stroke aphasia may induce quantitative but not qualitative
      alterations of pause patterns during speech, and further suggest that long pauses
      may serve as an index of internal cognitive processes supporting sentence
      planning. Our findings are discussed within the context of pause pattern
      quantification strategies as potential markers of cognitive changes in aphasia,
      further stressing the importance of such measures as an integral part of language
      assessment in clinical populations.

PMID- 29634962
TI  - Fabrication and characterization of genipin cross-linked chitosan/gelatin
      hydrogel for pH-sensitive, oral delivery of metformin with an application of
      response surface methodology.
AB  - In this study, central composite design was utilized for the preparation and
      optimization of chitosan-gelatin hydrogel films containing metformin using
      different concentrations of genipin as crosslinking agent. Solvent evaporation
      technique was used to develop hydrogel films. The formulated hydrogels were
      subjected to study the drug release in the simulated gastric pH1.2 for 3h.
      Initial burst release was observed from hydrogel during the first 2h of
      dissolution in gastric simulated environment. Different polymer ratios in
      formulation showed significant influence on T50% and dynamic swelling of
      hydrogel. The highest T50% was observed at 40.23min and dynamic swelling at 9.1.
      It was observed that by changing the polymer ratio with cross-linker, release
      rate of metformin could be modified. Cross-linker also affects the release rate
      as its concentration increases, the release rate decreases. The physical state of
      hydrogel was investigated by scanning electron microscope. It indicated the
      uniform presence of drug crystals in hydrogel matrix system. Fourier transform
      infrared spectroscopy (FTIR) confirmed the presence of hydrogen and ionic bonds
      between polymers and crosslinking agent leaving the drug intact in the matrix
      system. Scanning electron microscopy (SEM) images confirmed the uniform drug
      distribution. As per conclusion, the immediate release, pH sensitive, hydrogel
      formulation with good safety profile can be successfully fabricated by using CHI
      and GLN polymers with varying concentration of crosslinking agent.

PMID- 29634963
TI  - Immobilization of dextransucrase on functionalized TiO2 supports.
AB  - The TiO2 based hybrid supports with different functional groups (amino,
      glutaraldehyde or epoxy) were prepared and their influence on immobilization of
      dextransucrase (DS) was studied. Novel synthetic route for surface modification
      of TiO2 with amino and glutaraldehyde groups was developed taking advantage of
      charge transfer complex (CTC) formation between surface Ti atoms and salicylate
      type of ligand (5-aminosalicylic acid (5-ASA)). The proposed coordination of 5
      ASA to the surface of TiO2 powder and optical properties of CTC was presented.
      The pristine TiO2 and amino functionalized TiO2 have higher sorption capacity for
      DS (12.6 and 12.0mgg-1, respectively) compared to glutaraldehyde and epoxy
      activated supports (9.6 and 9.8mgg-1, respectively). However, immobilized enzyme
      to either glutaraldehyde or epoxy functionalized TiO2 have almost two times
      higher expressed activities compared to pristine TiO2 support (258, 235 and
      142IUg-1, respectively). Thermal stability of enzyme immobilized on
      glutaraldehyde and epoxy functionalized supports was studied at 40 degrees C, as
      well as operational stability under long-run working conditions in repeated
      cycles. After five cycles, DS imobilized on glutaraldehyde activated support
      retained almost 70% of its initial expressed activity, while, after five cycles,
      performance of DS immobilized on epoxy activated support was significantly lower
      (15%).

PMID- 29634964
TI  - Effect of sonication and gamma-irradiation on the properties of pea (Pisum
      sativum) and vetch (Vicia villosa) starches: A comparative study.
AB  - In present study, the physicochemical, functional and pasting properties of
      starch obtained from commercially used pea were compared with vetch, an
      underutilized pulse variety. Starch from each cultivar was subjected to
      sonication (33kHz for 45min) and a dual treatment in which sonication was
      followed by irradiation (5kGy). Apparent amylose content of the starch from two
      varieties varied significantly (p>0.05) from 31.08-27.58g/100g. Sonication and
      dual treatment decreased the amylose content of starches. Syneresis varied more
      or less insignificantly (p<0.05) upon sonication. However, upon dual treatment,
      syneresis decreased significantly (p>0.05) from 47.82-35.22g/100g (pea) and 46.36
      26.98g/100g (vetch) during the storage period of 120h. A combined effect of
      sonication and irradiation treatment significantly (p>0.05) changed the
      functional properties and pasting characteristics of starches. The samples that
      received the sonication treatment alone varied non-significantly from native pea
      and vetch starch in their physicochemical, functional and pasting properties.

PMID- 29634965
TI  - Incorporation of ZnO nanoparticles into heparinised polyvinyl alcohol/chitosan
      hydrogels for wound dressing application.
AB  - Available wound dressings have some major deficiencies including low water vapor
      transmission rate (WVTR), low absorption of wound fluids, and not providing a
      suitable and moist environment for wound healing. The main advantage of hydrogels
      is giving aid to the creation of a moist and cool environment for wound healing
      and providing high water vapor permeability along with preventing penetration of
      microbes into the wound surface. Therefore, hydrogels of heparinized polyvinyl
      alcohol (PVA)/chitosan (CS)/nano zinc oxide (nZnO) were prepared to be used as
      wound dressing. Samples were characterized via infrared spectrometry (FTIR), X
      ray diffraction (XRD) and scanning electron microscope (SEM). In addition, other
      properties including swelling ratio, water vapor transmission rate, the size of
      pores, mechanical and thermal properties, cell viability, and antibacterial
      efficiency were investigated. Water vapor permeability, porosity, and swelling
      ratio showed a wide range of numerical values that facilitate the use of provided
      samples as ideal wound dressings. Besides, investigating mechanical and thermal
      properties exhibited the improvement of mentioned properties by adding nano zinc
      oxide. Furthermore, Heparin loading was conducted on optimum samples. Heparin
      release rate decreased and was more sustained by adding nanoparticles compared to
      hydrogel wound dressings without nZnO. Cell viability of bionanocomposite samples
      showed no toxicity after loading nanoparticles and this value was >70% for all
      samples. Antibacterial properties of hydrogel samples can effectively protect
      wounds especially with an increase nZnO content. Hence, these hydrogels were
      found applicable as robust wound dressings.

PMID- 29634966
TI  - Magnetic biocatalysts of pectinase and cellulase: Synthesis and characterization
      of two preparations for application in grape juice clarification.
AB  - In the present study, we prepared two different magnetic biocatalysts of
      pectinase and cellulase: carrier-free magnetic CLEAs (CLEA-MP*) and
      immobilization on glutaraldehyde-activated magnetite (Enz-Glu-MP*). The
      biocatalysts were compared to their magnetic properties, immobilization
      parameters, stability and grape juice clarification. Enz-Glu-MP* presented higher
      magnetic properties than CLEA-MP*, whereas this presented higher surface area and
      pore volume. The KM of the enzyme immobilized on Enz-Glu-MP* was 25.65mM, lower
      in comparison to the CLEA-MP* (33.83mM). On the other hand, CLEA-MP* was the most
      active and stable biocatalyst, presenting higher recovered activity (33.4% of
      cellulase), higher thermal stability (2.39 stabilization factor) and improved
      reusability (8cycles). The integration of magnetic technology with enzymatic
      immobilization emerges as a possibility to increase the recover and reuse of
      biocatalysts for application in juice technology.

PMID- 29634967
TI  - Immunochemical studies on native and glycated LDL - An approach to uncover the
      structural perturbations.
AB  - Glycation initiates with the non-enzymatic reaction of amino group of proteins
      and lipoproteins by carbonyl group of sugar moiety and intermediates of glycative
      stress such as methylglyoxal (MG). The initial glycation leads to the formation
      of early glycation products (Amadori products) which undergo rearrangement,
      cyclization and dehydration to form advanced glycation end products (AGEs). The
      main objective of the present study is to investigate the non-enzymatic glycation
      of low density lipoprotein (LDL) by MG at different concentration and at
      increasing incubation time period in vitro. This modification may increase the
      formation of Amadori products and AGEs which are physico-chemically characterized
      with respect to the extent of LDL modification. Additionally, immunogenicity of
      native and MG modified LDL (MG-LDL) was probed in female rabbits in vivo.
      Immunogenicity of MG-LDL was found to be highly immunogenic, eliciting high titer
      immunogen-specific antibodies while native form of LDL is less immunogenic.
      Furthermore, the histopathology and immune-fluorescence studies suggest that the
      kidney section of immunized rabbits exhibit the presence of immune complex (MG
      LDL-IgG) deposition in the glomerular basement membrane (GBM).

PMID- 29634968
TI  - Integrated multi-spectroscopic and molecular docking techniques to probe the
      interaction mechanism between maltase and 1-deoxynojirimycin, an alpha
      glucosidase inhibitor.
AB  - Interaction mechanism of an antidiabetic agent, 1-deoxynojirimycin (DNJ) with its
      target protein alpha-glucosidase (maltase), was investigated by kinetics,
      fluorescence spectroscopy, UV-vis spectroscopy, circular dichroism, dynamic light
      scattering coupled with molecular docking analysis. It was found that DNJ
      reversibly inhibited activity of maltase through a mixed-type manner with IC50 of
      (1.5+/-0.1) MUM and inhibition constant Ki of (2.01+/-0.02) MUM. Fluorescence
      data and UV-vis information confirmed that the intrinsic fluorescence of maltase
      was quenched by DNJ through a dynamic quenching procedure due to the collision of
      them. The calculated thermodynamic parameters including enthalpy change, entropy
      change and Gibbs free energy change indicated that their binding was spontaneous
      and the driven force was hydrophobic interaction. Besides, circular dichroism
      analysis displayed that their binding resulted conformational changes of maltase,
      characterizing by a decrease of alpha-helix and an increase in beta-sheet.
      Dynamic light scattering measurements demonstrated the reduction in the
      hydrodynamic radii of maltase. Further molecular docking revealed that DNJ formed
      hydrogen bonds with catalytic residues Asp68, Arg212, Asp214, Glu276, Asp349 and
      Arg439 of maltase, then inhibited the enzyme activity by occupying catalytic
      center. This study provided a comprehensively understanding about the action
      mechanism of DNJ on maltase.

PMID- 29634969
TI  - Milk fat globule membrane protein promotes C2C12 cell proliferation through the
      PI3K/Akt signaling pathway.
AB  - Milk fat globule membrane (MFGM) protein is known to have several health
      benefits, including an anti-sarcopenia effect; however, its mechanism is unclear.
      The aim of this study was to investigate the potential mechanism of action of the
      MFGM protein. The MFGM protein was extracted and separated into 4 fractions, and
      Fraction 2 (57% of total MFGM) demonstrated the greatest effect on C2C12 cell
      proliferation. Milk fat globule-EGF factor 8 (MFG-E8) accounted for 82.35% of the
      MFGM protein. The effects of whole Fraction 2 (100MUg/mL, 200MUg/mL and
      300MUg/mL) on cell proliferation and morphology were measured. Using qRT-PCR or a
      Western blot assay, several regulatory factors, e.g., PI3K P85alpha, p-pI3K
      p85alpha (Tyr 508), Akt, p-Akt (Ser 473), mTOR and p-mTOR (Ser 2448), were
      measured in cells incubated with 200MUg/mL of Fraction 2 with or without
      wortmannin. The results demonstrated that Fraction 2 induced C2C12 cell
      proliferation in a dose-dependent manner, upregulated the mRNA expression of mTOR
      and p70S6K, and activated PI3K, Akt, mTOR and P70S6K phosphorylation; however,
      Fraction 2 inhibited FOXO3a and 4E-BP. The results demonstrate that the MFGM
      protein, predominantly MFG-E8, promotes cell proliferation through the
      PI3K/Akt/mTOR signaling pathway. This study elucidated the molecular mechanism of
      the MFGM protein, primarily MFG-E8, in promoting C2C12 cell proliferation via the
      PI3K/Akt/mTOR/P70S6K signal pathway.

PMID- 29634970
TI  - Injectable self-healing carboxymethyl chitosan-zinc supramolecular hydrogels and
      their antibacterial activity.
AB  - Injectable and self-healing hydrogels have found numerous applications in drug
      delivery, tissue engineering and 3D cell culture. Herein, we report an injectable
      self-healing carboxymethyl chitosan (CMCh) supramolecular hydrogels cross-linked
      by zinc ions (Zn2+). Supramolecular hydrogels were obtained by simple addition of
      metal ions solution to CMCh solution at an appropriate pH value. The mechanical
      properties of these hydrogels were adjustable by the concentration of Zn2+. For
      example, the hydrogel with the highest concentration of Zn2+ (CMCh-Zn4) showed
      strongest mechanical properties (storage modulus~11,000Pa) while hydrogel with
      the lowest concentration of Zn2+ (CMCh-Zn1) showed weakest mechanical properties
      (storage modulus~220Pa). As observed visually and confirmed rheologically, the
      CMCh-Zn1 hydrogel with the lowest Zn2+ concentration showed thixotropic property.
      CMCh-Zn1 hydrogel also presented injectable property. Moreover, the antibacterial
      properties of the prepared supramolecular hydrogels were studied against
      Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) by agar well
      diffusion method. The results revealed Zn2+ dependent antibacterial properties
      against both kinds of strains. The inhibition zones were ranging from ~11-24mm
      and ~10-22mm against S. aureus and E. coli, respectively. We believe that the
      prepared supramolecular hydrogels could be used as a potential candidate in
      biomedical fields.

PMID- 29634971
TI  - Recent advances in polysaccharides from Ophiopogon japonicus and Liriope spicata
      var. prolifera.
AB  - O. japonicus and L. spicata var. prolifera are distinguished as sources of highly
      promising yin-tonifying medicinals, namely Ophiopogonis Radix and Liriopes Radix.
      Liriopes Radix is generally medicinally used as a substitute for Ophiopogonis
      Radix in various prescriptions due to their extremely similar nature.
      Ophiopogonis Radix and Liriopes Radix are both very rich in bioactive
      polysaccharides, especially beta-fructans. Over the past twelve years, except for
      work on physical entrapment and chemical modification of obtained beta-fructans,
      the vast majority of studies are carried out to investigate the bioactivities of
      O. japonicus polysaccharides (OJP) and L. spicata var. prolifera polysaccharides
      (LSP), mainly including anti-diabetes, immunomodulation, anti-inflammation,
      antioxidation, anti-obesity, cardiovascular protection, etc. In addition, OJP and
      LSP are considered to have the potential to regulate intestinal flora. The main
      purpose of this review is to provide systematically reorganized information on
      structural characteristics and bioactivities of OJP and LSP to support their
      further therapeutic potentials and sanitarian functions.

PMID- 29634972
TI  - Unravelling variation in feeding, social interaction and growth patterns among
      pigs using an agent-based model.
AB  - Domesticated pigs, Sus scrofa, vary considerably in feeding, social interaction
      and growth patterns. This variation originates partly from genetic variation that
      affects physiological factors and partly from behavioural strategies (avoid or
      approach) in competitive food resource situations. Currently, it is unknown how
      variation in physiological factors and in behavioural strategies among animals
      contributes to variation in feeding, social interaction and growth patterns in
      animals. The aim of this study was to unravel causation of variation in these
      patterns among pigs. We used an agent-based model to explore the effects of
      physiological factors and behavioural strategies in pigs on variation in feeding,
      social interaction and growth patterns. Model results show that variation in
      feeding, social interaction and growth patterns are caused partly by chance, such
      as time effects and coincidence of conflicts. Furthermore, results show that
      seemingly contradictory empirical findings in literature can be explained by
      variation in pig characteristics (i.e. growth potential, positive feedback,
      dominance, and coping style). Growth potential mainly affected feeding and growth
      patterns, whereas positive feedback, dominance and coping style affected feeding
      patterns, social interaction patterns, as well as growth patterns. Variation in
      behavioural strategies among pigs can reduce aggression at group level, but also
      make some pigs more susceptible to social constraints inhibiting them from
      feeding when they want to, especially low-ranking pigs and pigs with a passive
      coping style. Variation in feeding patterns, such as feeding rate or meal
      frequency, can indicate social constraints. Feeding patterns, however, can say
      something different about social constraints at group versus individual level. A
      combination of feeding patterns, such as a decreased feed intake, an increased
      feeding rate, and an increased meal frequency might, therefore, be needed to
      measure social constraints at individual level.

PMID- 29634973
TI  - Subgroups of adolescents differing in physical and social environmental
      preferences towards cycling for transport: A latent class analysis.
AB  - In order to be able to tailor environmental interventions to adolescents at risk
      for low levels of physical activity, the aim of the present study is to identify
      subgroups of adolescents with different physical and social environmental
      preferences towards cycling for transport and to determine differences in
      individual characteristics between these subgroups. In this experimental study,
      882 adolescents (12-16 years) completed 15 choice tasks with manipulated
      photographs. Participants chose between two possible routes to cycle to a
      friend's house which differed in seven physical micro-environmental factors,
      cycling distance and co-participation in cycling (i.e. cycling alone or with a
      friend). Latent class analysis was performed. Data were collected from March till
      October 2016 across Flanders (Belgium). Three subgroups could be identified.
      Subgroup 1 attached most importance to separation of the cycle path and safety
      related aspects. Subgroup 2 attached most importance to being able to cycle
      together with a friend and had the highest percentage of regular cyclists. In
      subgroup 3, the importance of cycling distance clearly stood out. This subgroup
      included the lowest percentage of regular cyclists. Results showed that in order
      to stimulate the least regular cyclists, and thus also the subgroup most at risk
      for low levels of active transport, cycling distances should be as short as
      possible. In general, results showed that providing well-separated cycle paths
      which enable adolescents to cycle side by side and introducing shortcuts for
      cyclists may encourage different subgroups of adolescents to cycle for transport
      without discouraging other subgroups.

PMID- 29634974
TI  - Assessing the impact of the heart of New Ulm Project on cardiovascular disease
      risk factors: A population-based program to reduce cardiovascular disease.
AB  - The Heart of New Ulm Project (HONU), is a population-based project designed to
      reduce modifiable cardiovascular disease (CVD) risk factors in the rural
      community of New Ulm, MN. HONU interventions address multiple levels of the
      social-ecological model. The community is served by one health system, enabling
      the use of electronic health record (EHR) data for surveillance. The purpose of
      this study was to assess if trends in CVD risk factors and healthcare utilization
      differed between a cohort of New Ulm residents age 40-79 and matched controls
      selected from a similar community, using EHR data from baseline (2008-2009)
      through three follow up time periods (2010-2011, 2012-2013, 2014-2015). Matching,
      using covariate balance sparse technique, yielded a sample of 4077 New Ulm
      residents and 4077 controls. We used mixed effects longitudinal models to examine
      trends over time between the two groups. Blood pressure, total cholesterol, low
      density lipoprotein-cholesterol, and triglycerides showed better management in
      New Ulm over time compared to the controls. The proportion of residents in New
      Ulm with controlled blood pressure increased by 6.2 percentage points compared to
      an increase of 2 points in controls (p < 0.0001). As the cohort aged, 10-year
      ASCVD risk scores increased less in New Ulm (5.1) than the comparison community
      (5.9). The intervention and control community did not differ with regard to
      inpatient stays, smoking, or glucose. Findings suggest efficacy for the HONU
      project interventions for some outcomes.

PMID- 29634975
TI  - The clinicopathological significance of micropapillary pattern in colorectal
      cancers.
AB  - The aim of the present study is to elucidate the clinicopathological significance
      and prognostic role of micropapillary pattern (MPP) in colorectal cancer (CRC).
      We investigated the correlation between the presence of MPP and
      clinicopathological characteristics and prognosis in 266 CRCs. In addition, the
      clinicopathological significance of MPP in mucin pools was investigated and
      compared to pure MPP, which is not associated with mucin pools. MPP, regardless
      of its proportion in the overall tumor, was found in 74 of 266 CRCs (27.8%). The
      rate of MPP in proportions >=5% was 9.4% (25 of 266 cases). CRC with MPP showed
      higher rates of vascular and lymphatic invasion, higher metastatic lymph node
      ratio, and higher pT stage compared to CRC without MPP. In addition, increasing
      proportion of MPP in overall tumor showed more frequent vascular and lymphatic
      invasions (P = .002 and P = .008, respectively). Among 74 CRCs with MPP, 25 CRCs
      were found in mucin pools (33.8%). These cases were more right-sided and poorly
      differentiated with less frequent lymphatic invasion and lymph node metastasis,
      compared to CRCs with pure MPP. The presence of MPP significantly correlated with
      worse overall survival (P = .010). In 74 CRCs with MPP, overall survival
      significantly differed between pure MPP and MPP in mucin pools (P = .003). Taken
      together, our data suggest that the presence of MPP significantly correlated with
      aggressive tumor behavior and worse survival in CRC. In addition, the
      clinicopathological significance of MPP in mucin pools differed from CRC with
      pure MPP.

PMID- 29634976
TI  - High expression of synthesis of cytochrome c oxidase 2 and TP53-induced
      glycolysis and apoptosis regulator can predict poor prognosis in human lung
      adenocarcinoma.
AB  - Synthesis of cytochrome c oxidase 2 (SCO2) and TP53-induced glycolysis and
      apoptosis regulator (TIGAR) are 2 p53-mediated proteins that can play a
      regulatory role in cancer energy metabolism. However, no study has examined the
      association of SCO2 and TIGAR with the prognosis of patients with lung
      adenocarcinoma (AC). In our study, the expression of SCO2 and TIGAR proteins in
      lung AC was detected, and the potential relation to prognosis was evaluated,
      aiming to take a further view of lung AC progression. Quantum dots-based
      immunofluorescence histochemistry staining was performed to observe the
      expression of p53, SCO2, and TIGAR in 75 specimens of lung AC. Of these, 51
      (68.0%) showed high expression of SCO2, and 59 (78.7%) showed high expression of
      TIGAR. High TIGAR expression was significantly associated with a history of
      smoking (P = .017) and being male (P = .006). The correlation between high SCO2
      expression and age also was significant (P = .042). Moreover, high TIGAR
      expression was positively correlated with high SCO2 expression (P = .019; rs =
      0.271). High expression of the SCO2 and TIGAR proteins predicted poorer survival
      and a higher mortality rate (P = .024 and .030, respectively). High expression of
      SCO2 and TIGAR proteins is significantly associated with lung AC progression,
      suggesting their potential use as prognostic markers and therapeutic targets.

PMID- 29634977
TI  - Genomic profile of appendiceal goblet cell carcinoid is distinct compared to
      appendiceal neuroendocrine tumor and conventional adenocarcinoma.
AB  - Goblet cell carcinoid (GCC) is a rare appendiceal tumor with unique morphologic
      features that shows glandular and neuroendocrine differentiation on
      immunohistochemistry. An additional component of adenocarcinoma (AC) can be
      present (GCC-AC). Both GCC and GCC-AC are staged and treated like AC. The
      histogenesis and genetic alterations underlying GCC and GCC-AC are unclear.
      Capture-based next-generation DNA sequencing targeting 479 cancer genes was
      performed on 19 appendiceal tumors: 4 GCC, 9 GCC-AC, 3 neuroendocrine tumors
      (NET), and 3 AC (2 conventional, 1 mucinous). Somatic coding mutations were not
      seen in any NET. Pathogenic (P)/likely pathogenic (LP) mutations were present in
      1 GCC, 8 GCC-AC and all 3 AC cases. P/LP mutations in chromatin remodeling genes
      were seen in 4 (44.4%) GCC-AC cases, but not in NET, GCC or AC. In GCC-AC, P/LP
      mutations in ARID1A and RHOA were each present in 3 cases, and KDM6A and SOX9
      mutations were each seen in 2 cases. APC and KRAS mutations were present in 1
      conventional AC case, but were not observed in any GCC or GCC-AC. This limited
      series reveals mutations in SOX9, RHOA, and chromatin-modifier genes in goblet
      cell tumors, and shows that the mutational profile of GCC/GCC-AC is distinct from
      NET and conventional appendiceal AC.

PMID- 29634978
TI  - Clinical implication of programmed cell death-1 ligand-1 expression in tonsillar
      squamous cell carcinoma in association with intratumoral heterogeneity, human
      papillomavirus, and epithelial-to-mesenchymal transition.
AB  - Programmed cell death-1 ligand-1 (PD-L1), essential for immune evasion, is a
      potential candidate for pathogenesis and therapeutic target of human
      papillomavirus (HPV)-positive tonsillar squamous cell carcinomas (TSCCs).
      MET/hepatocyte growth factor signaling and transcription factors involved in
      epithelial-to-mesenchymal transition (EMT) upregulate PD-L1, which can contribute
      to clinical outcome. Intratumoral heterogeneity of PD-L1 expression is of
      clinical importance in selection bias due to false-negative patient enrollment.
      However, the clinicopathological features, prognostic value, and coexpressed
      molecules of PD-L1 remain unclear in TSCCs. PD-L1 expression was evaluated via
      immunohistochemistry using a specific monoclonal antibody (SP142) between whole
      tissue and tissue microarray (TMA) sections of 79 tumors (5% cutoff value with
      weak staining). Expressions of EMT markers (TWIST1, Snail, and SNIP1) and
      MET/hepatocyte growth factor were also analyzed. Staining of the TMA sections
      showed 78.5% concordance rate to the whole section. PD-L1 positivity and its
      intratumoral heterogeneity were 29.1% and 15.2% of TSCCs by whole section,
      respectively. PD-L1 positivity was prevalent in females, HPV-positive tumors
      without base of tongue invasion, and SNIP1-overexpressed tumors. SNIP1
      overexpression, unmethylated TWIST1, smoking, and poorly differentiated tumors
      were predictive for PD-L1 overexpression. PD-L1 positivity was a favorable
      independent prognostic factor. Subgroup analyses according to the coexpression of
      PD-L1 with HPV, SNIP1, or unmethylated TWIST1 indicated the best clinical outcome
      than any other subgroups. In conclusion, intratumoral heterogeneity of PD-L1
      expression was frequent, warranting a caution in punching TMA cores. A combined
      analysis of PD-L1 with EMT and HPV may define a characteristic subset of patients
      and prognostic group.

PMID- 29634979
TI  - Comparison of thyroid transcription factor-1 expression by 2 monoclonal
      antibodies in schwannomas: the chosen clone matters-reply.

PMID- 29634980
TI  - Somatic polymerase epsilon mutations as another route leading to loss of DNA MMR
      protein expression in endometrial carcinoma.

PMID- 29634981
TI  - Comparison of thyroid transcription factor-1 expression by 2 monoclonal
      antibodies in schwannomas: the chosen clone matters.

PMID- 29634982
TI  - Nurr1: A vital participant in the TLR4-NF-kappaB signal pathway stimulated by
      alpha-synuclein in BV-2 cells.
AB  - Parkinson's disease (PD) is a multi-factorial neurodegenerative disease. Abnormal
      alpha-synuclein protein aggregate and sustained microglia activation contribute
      to the pathogenic processes of PD. However, the relationship between alpha
      synuclein and microglia-mediated neuroinflammation remains unclear. We purified
      alpha-synuclein after overexpression in Escherichia coli and then used it to
      stimulate BV-2 cells or primary microglia cells from wild type or toll-like
      receptor 4 (TLR4)-defective mice. Enzyme linked immunosorbent assay (ELISA) and
      real-time PCR results confirmed that alpha-synuclein could enhance the production
      of tumor necrosis factor alpha (TNF-alpha) through TLR4 activation. Western
      blotting results confirmed the involvement of the TLR4/PI3K/AKT/GSK3beta signal
      pathway in the inflammatory response. Nuclear factor kappa B (NF-kappaB) could
      translocate to the nucleus, promoting the expression of TNF-alpha when stimulated
      by alpha-synuclein in BV-2 cells. Nurr1 suppressed the production of TNF-alpha
      via interaction with NF-kappaB/p65 and inhibiting its nuclear translocation. In
      addition, both NF-kappaB and Nurr1 appeared to be regulated by the TLR4-mediated
      signal pathway. Our work demonstrated that TLR4 recognized alpha-synuclein and
      activated downstream signaling mechanisms leading to the release of pro
      inflammatory mediators that are contra-balanced by Nurr1 expression. In
      conclusion, Nurr1 is a novel participant in the neuroinflammation stimulated by
      alpha-synuclein, thus the regulation of Nurr1 may be a novel neuroprotective
      target for PD treatment.

PMID- 29634983
TI  - Peripheral GABAA receptor-mediated signaling facilitates persistent inflammatory
      hypersensitivity.
AB  - Unlike in the central nervous system (CNS), in the adult peripheral nervous
      system (PNS), activation of GABAA receptors (GABAAR) is excitatory because of the
      relatively high concentration of intracellular chloride in these neurons. Indeed,
      exogenous GABA and muscimol, a GABAAR agonist, exacerbate acute inflammatory
      hypersensitivity in rodents. However, it remains unclear whether peripheral
      GABAAR and the endogenous GABA play an important role in persistent inflammatory
      hypersensitivity. In this study, we thus investigated how peripheral GABAAR
      affects pain hypersensitivity by using the complete Freund's adjuvant (CFA)
      induced persistent inflammatory pain mouse model. We found that intraplantar
      (i.pl.) administration of GABAAR antagonists, picrotoxin, and 1(S),9(R)-(-)
      bicuculline methiodide significantly inhibited both spontaneous nociceptive (paw
      licking and flinching) behavior and mechanical hypersensitivity in CFA-injected
      mice at day 3 (D3), but not in naive mice. Interestingly, CFA-induced mechanical
      hypersensitivity was significantly reversed by anti-GABA antibody (anti-GABA,
      i.pl.). In addition, RT-qPCR revealed that glutamate decarboxylase Gad1 (GAD 67)
      and Gad2 (GAD 65) mRNA expression was also upregulated in the ipsilateral hind
      paw of CFA-injected mice at D3. Finally, 5alpha-pregnan-3alpha-ol-20-one
      (3alpha,5alpha-THP), a selective positive allosteric modulator of GABAAR,
      produced mechanical hypersensitivity in naive mice in a dose-dependent manner.
      Taken together, our results indicate that peripheral GABAAR and endogenous GABA,
      possibly produced by the inflamed tissue, potentiate CFA-induced persistent
      inflammatory hypersensitivity, suggesting that they can be used as a therapeutic
      target for alleviating inflammatory pain.

PMID- 29634984
TI  - Environmental enrichment effects on synaptic and cellular physiology of
      hippocampal neurons.
AB  - Exposure of rodents to an enriched environment (EE) has been shown to reliably
      increase performance on hippocampus-dependent learning and memory tasks, compared
      to conspecifics living in standard housing conditions. Here we review the EE
      related functional changes in synaptic and cellular properties for neurons in the
      dentate gyrus and area CA1, as assessed through in vivo and ex vivo
      electrophysiological approaches. There is a growing consensus of findings
      regarding the pattern of effects seen. Most prominently, there are changes in
      cellular excitability and synaptic plasticity in CA1, particularly with short
      term and/or periodic exposure to EE. Such changes are much less evident after
      longer term continuous exposure to EE. In the dentate gyrus, increases in
      synaptic transmission as well as cell excitability become evident after short
      term EE exposure, while the induction of long-term potentiation (LTP) in the
      dentate is remarkably insensitive, even though it is reliably enhanced by
      voluntary running. Recent evidence has added a new dimension to the understanding
      of EE effects on hippocampal electrophysiology by revealing an increased sparsity
      of place cell representations after long periods of EE treatment. It is possible
      that such connectivity change is one of the key factors contributing to the
      enhancement of hippocampus-dependent spatial learning over the long-term, even if
      there are no obvious changes in other markers such as LTP.

PMID- 29634985
TI  - Synergistic effect of caffeic acid phenethyl ester with caspofungin against
      Candida albicans is mediated by disrupting iron homeostasis.

PMID- 29634986
TI  - Use of physiologically based kinetic modelling-facilitated reverse dosimetry to
      convert in vitro cytotoxicity data to predicted in vivo liver toxicity of
      lasiocarpine and riddelliine in rat.
AB  - Lasiocarpine and riddelliine are pyrrolizidine alkaloids (PAs) present in food
      and able to cause liver toxicity. The aim of this study was to investigate
      whether physiologically based kinetic (PBK) modelling-facilitated reverse
      dosimetry can adequately translate in vitro concentration-response curves for
      toxicity of lasiocarpine and riddelliine to in vivo liver toxicity data for the
      rat. To this purpose, PBK models were developed for lasiocarpine and riddelliine,
      and predicted blood concentrations were compared to available literature data to
      evaluate the models. Concentration-response curves obtained from in vitro
      cytotoxicity assays in primary rat hepatocytes were converted to in vivo dose
      response curves from which points of departure (PODs) were derived and that were
      compared to available literature data on in vivo liver toxicity. The results
      showed that the predicted PODs fall well within the range of PODs derived from
      available in vivo toxicity data. To conclude, this study shows the proof-of
      principle for a method to predict in vivo liver toxicity for PAs by an
      alternative testing strategy integrating in vitro cytotoxicity assays with in
      silico PBK modelling-facilitated reverse dosimetry. The approach may facilitate
      prediction of acute liver toxicity for the large number of PAs for which in vivo
      toxicity data are lacking.

PMID- 29634987
TI  - How category average reference points affect choice of sugary foods.
AB  - Improving diet quality is as important as it is difficult. Market-level
      information such as summary information in the form of an average (i.e., category
      average reference point [CARP]) discloses information otherwise difficult to
      obtain by comparing different products. The results of a choice-based conjoint
      experiment (N = 698) show that CARP affects food choice in multicue environments
      and interacts with source credibility in driving consumer acceptance of sugar
      content. In particular, the likelihood of choosing high amounts of sugar
      increases when a high CARP is provided by a credible source because of increased
      consumer acceptance of higher levels of that nutrient. Implications of the
      findings for research and public policy conclude the article.

PMID- 29634988
TI  - Determinants of knowledge and attitudes about sugar and the association of
      knowledge and attitudes with sugar intake among adults: A systematic review.
AB  - Efforts to reduce sugar intake levels have been primarily limited to increasing
      knowledge and changing attitudes. We conducted a systematic review to (1)
      identify factors influencing adults' knowledge and attitudes about sugar, and (2)
      determine if there is an association between knowledge and attitudes about sugar
      and sugar intake. We searched 15 electronic databases from inception to December
      2016 for English language publications including adults with relevant exposure
      and outcome measures. Findings were summarised meta-narratively. Of 3287 studies,
      22 studies (14 for objective one and 8 for objective two) were included.
      Individual (liking of sugary food), interpersonal (attitudes of peers) and
      environmental factors (media, health professionals and food labelling) influenced
      adults' knowledge and attitudes about sugar, at least to some extent. Overall,
      quality of the studies included in our review was weak, and evidence for the
      application of the Knowledge-Attitude-Behavior model for understanding sugar
      intake is limited. Protocol registered in the PROSPERO International prospective
      register of systematic reviews (registration number CRD42015027540).

PMID- 29634989
TI  - A mind cleared by walnut oil: The effects of polyunsaturated and saturated fat on
      extinction learning.
AB  - The treatment of anxiety-based psychopathology often hinges upon extinction
      learning. Research in nutritional neuroscience has observed that the regular
      consumption of perilla oil (50% alpha-linolenic acid (ALA)) facilitates
      extinction learning in rats (Yamamoto et al., 1988). However, acute facilitation
      of extinction learning by oils rich in ALA has not been reported for rats or
      humans, though the acute consumption of rapeseed oil (10% ALA) has been observed
      to improve cognitive processing speed in humans (Jones, Sunram-Lea, & Wesnes,
      2012). For this reason, the present laboratory work examined the effects of
      adding walnut oil (12% ALA) to a chocolate milkshake on the acquisition,
      generalization, and extinction of a fear-based prediction in young adults. It
      compared performance between subjects. The other participants consumed a similar
      milkshake with either an equicaloric amount of cream (saturated fat), or with no
      added fat (control). Acquisition and generalization of the fear-based prediction
      were similar for all groups. However, those who consumed walnut oil extinguished
      most rapidly and profoundly. Implications for extinction learning are discussed.

PMID- 29634990
TI  - ERPs differentiate the sensitivity to statistical probabilities and the learning
      of sequential structures during procedural learning.
AB  - Procedural learning facilitates the efficient processing of complex environmental
      stimuli and contributes to the acquisition of automatic behaviors. Although
      earlier findings suggest different temporal trajectories of the multiple learning
      processes within procedural learning, this has not been clarified at the level of
      neurocognitive correlates. Therefore, we investigated whether two prominent
      learning processes - statistical learning and sequence learning - can be
      distinguished using event-related brain potentials (ERPs) within the same
      experimental setting. Healthy young adults (N = 40) performed the Alternating
      Serial Reaction Time task while RTs and ERPs were measured time-locked to the
      onset of the task's stimuli. Both RT and N2 effects reflected the rapid
      acquisition of statistical probabilities. At the same time, these effects
      reflected the gradual learning of sequential structures. The amplitude change of
      the P3 reflected only gradual sequence learning. The P1 component was sensitive
      to both learning processes, which did not change as the task progressed. Our
      results altogether indicate that statistical learning and sequence learning
      develop differently at the level of both ERPs and overt responses. These findings
      could provide insight to the dynamic change of multiple parallel learning
      processes that occur during procedural memory formation.

PMID- 29634992
TI  - Bioresponsive release of insulin-like growth factor-I from its PEGylated
      conjugate.
AB  - PEGylation of protein ligands, the attachment of polyethylene glycol (PEG)
      polymers to a therapeutic protein, increases therapeutics' half-life but
      frequently comes at the cost of reduced bioactivity. We are now presenting a
      bioinspired strategy leading out of this dilemma. To this end, we selected a
      position within insulin-like growth factor I (IGF-I) for decoration with a
      PEG30kDa-modified protease-sensitive peptide linker (PSL) using a combination of
      enzymatic and chemical bioorthogonal coupling strategies. The PSL sequence
      responded to matrix metalloproteinases (MMP) to provide a targeted release in
      diseased tissue. The IGF-PSL-PEG conjugate had different binding protein
      affinity, cell proliferation, and endocytosis patterns as compared to the wild
      type. Exposure of the conjugate to elevated levels of activated MMPs, as present
      in inflamed tissues, fully reestablished the wild type properties through
      effective PSL cleavage. In conclusion, this bioinspired approach provided a
      blueprint for PEGylated therapeutics combining the pharmacokinetic advantages of
      PEGylation, while locally restoring the full suite of biological potential of
      therapeutics.

PMID- 29634993
TI  - "Life-bearing molecules" versus "life-embodying systems": Two contrasting views
      on the what-is-life (WIL) problem persisting from the early days of molecular
      biology to the post-genomic cell- and organism-level biology.
AB  - "What is life?" is an ultimate biological quest for the principle that makes
      organisms alive. This 'WIL problem' is not, however, a simple one that we have a
      straightforward strategy to attack. From the beginning, molecular biology tried
      to identify molecules that bear the essence of life: the double helical DNA
      represented replication, and enzymes were micro-actuators of biological
      activities. A dominating idea behind these mainstream biological studies relies
      on the identification of life-bearing molecules, which themselves are models of
      life. Another, prevalent idea emphasizes that life resides in the whole system of
      an organism, but not in some particular molecules. The behavior of a complex
      system may be considered to embody the essence of life. The thermodynamic view of
      life system in the early 20th century was remodeled as physics of complex systems
      and systems biology. The two views contrast with each other, but they are no
      longer heritage of the historical dualism in biology, such as
      mechanism/materialism versus vitalism, or reductionism versus holism. These two
      views are both materialistic and mechanistic, and act as driving forces of modern
      biology. In reality, molecules function in a context of systems, whereas systems
      presuppose functional molecules. A key notion to reconcile this conflict is that
      subjects of biological studies are given before we start to study them. Cell- or
      organism-level biology is destined to the dialectic of molecules and systems, but
      this antagonism can be resolved by dynamic thinking involving biological
      evolution.

PMID- 29634991
TI  - Integrating in vitro and in silico approaches to evaluate the "dual
      functionality" of palmatine chloride in inhibiting and disassembling Tau-derived
      VQIVYK peptide fibrils.
AB  - BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative
      disorder which is characterized by the deposits of intra-cellular tau protein and
      extra-cellular amyloid-beta (Abeta) peptides in the human brain. Understanding
      the mechanism of protein aggregation and finding compounds that are capable of
      inhibiting its aggregation is considered to be highly important for disease
      therapy. METHODS: We used an in vitro High-Throughput Screening for the
      identification of potent inhibitors of tau aggregation using a proxy model; a
      highly aggregation-prone hexapeptide fragment 306VQIVYK311 derived from tau.
      Using ThS fluorescence assay we screened a library of 2401 FDA approved, bio
      active and natural compounds in attempt to find molecules which can efficiently
      modulate tau aggregation. RESULTS: Among the screened compounds, palmatine
      chloride (PC) alkaloid was able to dramatically reduce the aggregation propensity
      of PHF6 at sub-molar concentrations. PC was also able to disassemble preformed
      aggregates of PHF6 and reduce the amyloid content in a dose-dependent manner.
      Insights obtained from MD simulation showed that PC interacted with the key
      residues of PHF6 responsible for beta-sheet formation, which could likely be the
      mechanism of inhibition and disassembly. Furthermore, PC could effectively
      inhibit the aggregation of full-length tau and disassemble preformed aggregates.
      CONCLUSIONS: We found that PC possesses "dual functionality" towards PHF6 and
      full-length tau, i.e. inhibit their aggregation and disassemble pre-formed
      fibrils. GENERAL SIGNIFICANCE: The "dual functionality" of PC is valuable as a
      disease modifying strategy for AD, and other tauopathies, by inhibiting their
      progress and reducing the effect of fibrils already present in the brain.

PMID- 29634996
TI  - New mechanistic insights into memory processes.

PMID- 29634995
TI  - The pUL56 of pseudorabies virus variant induces downregulation of swine leukocyte
      antigen class I molecules through the lysosome pathway.
AB  - Pseudorabies virus (PRV) is the causative agent of pseudorabies (PR) which causes
      large economic losses for Chinese swine industry since breaking out in late 2011.
      As a member of herpesviruses, PRV is able to escape the host immune elimination
      and establish latency, resulting in persistent infection. Here, we report that a
      currently prevalent Chinese PRV variant down-regulated swine leukocyte antigen
      class I (SLA-I) molecules on the surface of PK-15 cells and targeted them for
      degradation through lysosome pathway. Viral pUL56 protein, independent of other
      viral proteins, was associated with this function by inducing degradation of
      cellular SLA-I heavy chain (HC) in a manner that was dependent on the lysosome
      machinery. In addition, pUL56 interacted with SLA-I HC and increased its
      ubiquitination. Further studies demonstrated that the late domains (PPXY motifs)
      of pUL56 were required for the ubiquitination and degradation of SLA-I HC by
      pUL56. Together, our findings reveal the mechanisms by which PRV interferes with
      cytotoxic T lymphocyte (CTL) responses and provide novel insights into the roles
      of PRV pUL56.

PMID- 29634994
TI  - Reduced regional volumes associated with total psychopathy scores in an adult
      population with childhood lead exposure.
AB  - Childhood lead exposure has been correlated to acts of delinquency and criminal
      behavior; however, little research has been conducted to examine its potential
      long term influence on behavioral factors such as personality, specifically
      psychopathic personality. Neuroimaging studies have demonstrated that the effects
      of childhood lead exposure persist into adulthood, with structural abnormalities
      found in gray and white matter regions involved in behavioral decision making.
      The current study examined whether measurements of adult psychopathy were
      associated with neuroanatomical differences in structural brain volumes for a
      longitudinal cohort with measured childhood lead exposure. We hypothesized that
      increased total psychopathy scores and increased blood lead concentration at 78
      months of age (PbB78) would be inversely associated with volumetric measures of
      gray and white matter brain structures responsible for executive and emotional
      processing. Analyses did not display a direct effect between total psychopathy
      score and gray matter volume; however, reduced white matter volume in the
      cerebellum and brain stem in relation to increased total psychopathy scores was
      observed. An interaction between sex and total psychopathy score was also
      detected. Females displayed increased gray matter volume in the frontal,
      temporal, and parietal lobes associated with increased total psychopathy score,
      but did not display any white matter volume differences. Males primarily
      displayed reductions in frontal gray and white matter brain volume in relation to
      increased total psychopathy scores. Additionally, reduced gray and white matter
      volume was associated with increased blood lead levels in the frontal lobes;
      reduced white matter volume was also observed in the parietal and temporal lobes.
      Females demonstrated gray and white matter volume loss associated with increased
      PbB78 values in the right temporal lobe, as well as reduced gray matter volume in
      the frontal lobe. Males displayed reduced white matter volumes associated with
      increased PbB78 values in the frontal, temporal, and parietal lobes. Comparison
      of the two primary models revealed a volumetric decrease in the white matter of
      the left prefrontal cortex associated with increased total psychopathy scores and
      increased blood lead concentration in males. The results of this study suggested
      that increased psychopathy scores in this cohort may be attributable to the
      neuroanatomical abnormalities observed and that childhood lead exposure may be
      influential to these outcomes.

PMID- 29634997
TI  - RNAi-mediated SYT14 knockdown inhibits the growth of human glioma cell line
      U87MG.
AB  - SYT14 (Synaptotagmin 14) participates in pathomechanical neurodegeneration and
      contributes to abnormal neurodevelopment. However, the functional mechanism of
      SYT14 in human glioma tumorigenesis remains unclear. In the present study, we
      measured the expression levels of SYT14 mRNA in human glioma cell lines, U373MG,
      U178, and U87MG and neural stem cells (NSC) cell line by RT-PCR, and used
      lentivirus-mediated small hairpin RNAs (shRNAs) to knock down SYT14 expression in
      U87MG cells. Changes in SYT14 expression were determined by real-time PCR. Cell
      proliferation and colony formation assays were used to analyze the role of SYT14
      in U87MG cell proliferation, and cell apoptosis was assessed by flow cytometry.
      SYT14 mRNA expression was detected in the three glioma cell lines, and was
      highest in the U87MG cell line. The RNAi-mediated knockdown of SYT14
      significantly decreased cell proliferation and colony formation in U87MG cells,
      and caused a moderate increase in apoptosis. Fewer S phase cells and more G2/M
      phase cells were observed. These data indicate that SYT14 is highly expressed in
      glioma cells, and may participate in glioma cell proliferation, apoptosis, and
      colony formation.

PMID- 29634998
TI  - Midazolam Attenuates Autophagy and Apoptosis Caused by Ketamine by Decreasing
      Reactive Oxygen Species in the Hippocampus of Fetal Rats.
AB  - Every year between 0.75% and 2% of pregnant women require surgery that is related
      to either the pregnancy or other medical problems in USA. Therefore, the
      neurodegeneration following anesthesia in a variety of animal models has
      attracted our attention. Neurotoxic effects of ketamine cannot be ignored. In
      contrast, some anesthetics, including midazolam, protect neurons and increase
      dendritic spine density. However, the mechanism of neuroprotection by midazolam
      is not clear, and whether midazolam can relieve the damage caused by ketamine is
      unknown. Therefore, in this study, we explored the effects of midazolam on
      ketamine anesthesia. We measured protein levels of cleaved-caspase-3 (c-caspase
      3), beclin-1, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax),
      autophagy-related gene 4 (ATG4), ATG5, p62 (SQSTM1), and the autophagy marker
      light chain 3 (LC3) in hippocampus by Western analysis. We also measured total
      antioxidant capacity (T-AOC), and levels of reactive oxygen species (ROS) and
      malondialdehyde (MDA) in hippocampus and PC12 cells. Results showed that ketamine
      induced apoptosis through activation of the mitochondrial pathway by increasing
      the expression of c-caspase-3 and Bax, and decreasing the expression of Bcl-2 at
      the protein level. Ketamine also increased the expression of LC3II and ATG5,
      proteins, decreased the expression of ATG4 and P62, and finally induced
      autophagy. Ketamine promoted the production of ROS and MDA, and reduced total
      antioxidant capacity (T-AOC); these effects were attenuated by midazolam. In
      conclusion, ketamine induces toxicity in human neurons through ROS-mediated
      activation of mitochondrial apoptotic pathway and autophagy. The harmful effects
      of ketamine can be ameliorated by midazolam.

PMID- 29634999
TI  - Expertise-Level-Dependent Functionally Plastic Changes During Motor Imagery in
      Basketball Players.
AB  - Motor imagery is the mental process of rehearsing or simulating a given action
      without overt movements. The aim of the present study is to examine plastic
      changes in relevant brain areas during motor imagery with increasing expertise
      level. Subjects (novices, intermediate and elite players) performed motor imagery
      of basketball throws under two experimental conditions (with-ball and without
      ball). We found that all basketball players exhibited better temporal congruence
      (between motor imagery and motor execution) and higher vividness of motor imagery
      than novices. The vividness of motor imagery was higher for the with-ball than
      for the without-ball conditions in all three subject groups. The results from
      functional magnetic resonance imaging (fMRI) showed three different patterns of
      cortical activation. Activation in the left middle frontal gyrus increased and
      that in the left supplementary motor area decreased with increasing levels of
      motor expertise. Importantly, brain activation in the left postcentral gyrus was
      the highest in the intermediate players compared to both novices and elite
      players. For the elite group, these three areas showed higher activation in the
      without-ball condition than the with-ball condition, while the opposite trend was
      found in intermediate players. Our findings suggest that the level of motor
      expertise may be related to high-order brain functions that are linked to
      different activation patterns in different brain areas.

PMID- 29635000
TI  - beta-dystroglycan is regulated by a balance between WWP1-mediated degradation and
      protection from WWP1 by dystrophin and utrophin.
AB  - Dystroglycan is a ubiquitous membrane protein that functions as a mechanical
      connection between the extracellular matrix and cytoskeleton. In skeletal muscle,
      dystroglycan plays an indispensable role in regulating muscle regeneration; a
      malfunction in dystroglycan is associated with muscular dystrophy. The regulation
      of dystroglycan stability is poorly understood. Here, we report that WWP1, a
      member of NEDD4 E3 ubiquitin ligase family, promotes ubiquitination and
      subsequent degradation of beta-dystroglycan. Our results indicate that dystrophin
      and utrophin protect beta-dystroglycan from WWP1-mediated degradation by
      competing with WWP1 for the shared binding site at the cytosolic tail of beta
      dystroglycan. In addition, we show that a missense mutation (arginine 440 to
      glutamine) in WWP1-which is known to cause muscular dystrophy in chickens
      increases the ubiquitin ligase-mediated ubiquitination of both beta-dystroglycan
      and WWP1. The R440Q missense mutation in WWP1 decreases HECT domain-mediated
      intramolecular interactions to relieve autoinhibition of the enzyme. Our results
      provide new insight into the regulation of beta-dystroglycan degradation by WWP1
      and other Nedd4 family members and improves our understanding of dystroglycan
      related disorders.

PMID- 29635001
TI  - A new role for mast cells as scavengers for clearance of erythrocytes damaged due
      to oxidative stress.
AB  - Anemia, inflammation, and oxidative stress are interconnected. Erythrocytes are
      continuously exposed to oxidative stress, normally and during inflammatory
      diseases. Systemic mastocytosis and genetic depletion of mast cells affect
      anemia. In the present study, a direct role for mast cells in clearance of
      erythrocytes was explored. We show, for the first time, direct phagocytosis of
      opsonized as well as oxidatively damaged erythrocytes in vitro by mast cell
      lines, bone marrow derived mast cells (BMMCs) and in vivo by murine peritoneal
      mast cells. Also, activated mast cells, as may be present in inflammatory
      conditions, showed a significantly higher uptake of oxidatively damaged
      erythrocytes than resting mast cells. This suggests the involvement of mast cells
      in erythrocyte clearance during oxidative stress or inflammatory disorders.
      Partial inhibition of phagocytosis by various inhibitors indicated that this
      process may be controlled by several pathways. Our study provides important
      evidence for a scavenging role for mast cells in anemia due to inflammation and
      oxidative stress.

PMID- 29635002
TI  - Impact of antiretroviral and tuberculosis therapies on CD4+ and CD8+ HIV/M.
      tuberculosis-specific T-cell in co-infected subjects.
AB  - BACKGROUND: Human Immunodeficiency Virus (HIV) infection is a risk factor for
      tuberculosis (TB). Antiretroviral therapy (ART) changed HIV clinical management
      but it is still unclear how pre-existing HIV/Mycobacterium tuberculosis (Mtb)
      specific CD4+ and CD8+ T-cells are restored. AIM: to evaluate the impact of ART
      and TB therapies on the functional and phenotypic profile of Mtb-specific antigen
      response of CD4+ and CD8+ T-cells in prospectively enrolled HIV-TB co-infected
      patients. METHODS: ART-naive HIV-infected patients, with or without active TB or
      latent TB infection (LTBI), were enrolled before and after starting ART and TB
      therapies. Peripheral blood mononuclear cells (PBMC) were stimulated overnight
      with Mtb and HIV antigens (GAG). Cytokine expression and phenotype profile were
      evaluated by flow cytometry. Cytomegalovirus (CMV) and staphylococcal enterotoxin
      B (SEB) were also used. RESULTS: The median of absolute number of CD4+ T-cells
      increased after ART and TB therapies in all groups analyzed, while the median of
      absolute number of CD8+ T-cells decreases in HIV and HIV-LTBI groups. Treatments
      significantly increased the frequency of Mtb-specific CD4+ T-cells in the HIV
      LTBI (p = 0.015) with a rise of the central memory compartment. The magnitude of
      the CD4+ T-cell response to HIV-GAG significantly increased in active TB (p =
      0.03), whereas the magnitude of CMV-specific CD4+ T-cell response decreased in
      all the groups. Similarly, the treatments increased the number of Mtb-specific
      CD8+ responders in both HIV-LTBI and HIV-TB groups, whereas the phenotype
      distribution was dependent on the antigens used and on the stage of
      infection/disease. CONCLUSIONS: After therapies the median of absolute number and
      the proportion of CD4+ T-cells increased in all groups whereas the median of
      absolute count and proportion of CD8+ T-cells decreased in the HIV and HIV-LTBI
      subjects. Interestingly, an increased frequency of CD4+ T-cell response to RD1
      proteins in HIV-LTBI subjects was found. These results contribute to a better
      understanding of the effect of ART and TB therapies on the modulation of Mtb
      specific CD4+ and CD8+ T-cells subsets.

PMID- 29635003
TI  - STAT3: The art of multi-tasking of metabolic and immune functions in obesity.
AB  - Signal transducer and activator of transcription 3 (STAT3) is a transcription
      factor that has recently attracted increased attention. Accumulating studies have
      demonstrated that STAT3 plays an important role in various diseases, such as
      cancer and ischemic injury. In light of the distinctive effects of STAT3 on the
      regulation of metabolism and immune responses, we present the elaborate network
      of STAT3 in obesity. In this review, we first introduce the general background of
      STAT3, including a discussion regarding the STAT family and the characterization
      and regulation of STAT3. Then, we describe the STAT3 signaling network and its
      pathophysiological roles in lipid and glucose metabolism and immune function.
      Finally, we highlight the research progress regarding STAT3 in obesity. The
      information presented here may be useful for the design of future studies and may
      highlight the potential of STAT3 as a future therapeutic target for obesity.

PMID- 29635004
TI  - Response to Shaw et al.

PMID- 29635005
TI  - Genetic diversification of chemokine CXCL16 and its receptor CXCR6 in primates.
AB  - Chemokine CXCL16 and its receptor CXCR6 are associated with a series of
      physiological and pathological processes in cooperative and stand-alone fashions.
      To shed insight into their versatile nature, we studied genetic variations of
      CXCL16 and CXCR6 in primates. Evolutionary analyses revealed that these genes
      underwent a similar evolutionary fate. Both genes experienced adaptive
      diversification with the phylogenetic division of cercopithecoids (Old World
      monkeys) and hominoids (humans, great apes, and gibbons) from their common
      ancestor. In contrast, they were conserved in the periods preceding and following
      the dividing process. In terms of the adaptive diversification between
      cercopithecoids and hominoids, the adaptive genetic changes have occurred in the
      mucin-like and chemokine domains of CXCL16 and the N-terminus and transmembrane
      helixes of CXCR6. In combination with currently available structural and
      functional information for CXCL16 and CXCR6, the parallels between the
      evolutionary footprints and the co-occurrence of adaptive diversification at some
      evolutionary stage suggest that interplay could exist between the diversification
      related amino acid sites, or between the domains on which the identified sites
      are located, in physiological processes such as chemotaxis and/or cell adhesion.

PMID- 29635006
TI  - A potential robust antiviral defense state in the common vampire bat: Expression,
      induction and molecular characterization of the three interferon-stimulated genes
      -OAS1, ADAR1 and PKR.
AB  - Bats are known to harbor many zoonotic viruses, some of which are pathogenic to
      other mammals while they seem to be harmless in bats. As the interferon (IFN)
      response represents the first line of defense against viral infections in
      mammals, it is hypothesized that activation of the IFN system is one of the
      mechanisms enabling bats to co-exist with viruses. We have previously reported
      induction of type I IFN in a cell line from the common vampire bat, Desmodus
      rotundus, upon polyinosinic:polycytidylic acid (poly(I:C)) stimulation. To deepen
      our knowledge on D. rotundus' IFN-I antiviral response, we molecularly
      characterized three interferon-stimulated genes (ISGs), OAS1, PKR and ADAR1,
      closely implicated in the IFN-I antiviral response, and tested their
      functionality in our cellular model. We first found that D. rotundus encoded two
      OAS1 paralogs, OAS1a and OAS1b, and that the functional domains of the four ISGs
      characterized were highly conserved with those of other mammals. Despite their
      significant transcription level in the absence of stimulation, the transcription
      of the four ISGs characterized was enhanced by poly(I:C). In addition, the
      transcription of OAS1a and OAS1b appears to be differentially regulated. These
      findings demonstrate an active ISG antiviral response in D. rotundus in which
      OAS1b may play an important role.

PMID- 29635007
TI  - Co-occurrence of mcr-1, mcr-4 and mcr-5 genes in multidrug-resistant ST10
      Enterotoxigenic and Shiga toxin-producing Escherichia coli in Spain (2006-2017).
AB  - Colistin is an antimicrobial polypeptide commonly employed for controlling and
      treating neonatal and post-weaning diarrhoea (PWD) diseases caused by
      Enterotoxigenic and Shiga toxin-producing Escherichia coli (ETEC and STEC). The
      plasmid-mediated colistin resistance gene, mcr-1 was first described in late 2015
      and, since then, multiple studies have reported its global distribution. In
      addition, five different mcr genes have been identified. The aim of this study
      was to characterise the colistin-resistant E. coli clonal groups implicated in
      PWD in farms of intensive pig production. Of 186 ETEC and STEC isolated in Spain
      from 2006 to 2017, 76.9% showed resistance to colistin. Of those, 102 were mcr-4
      carriers, 37 mcr-1 and 5 mcr-5, with co-occurrence of mcr-1/mcr-4, mcr-1/mcr-5
      and mcr-4/mcr-5 in five isolates. Three different mcr-4 variants were detected,
      including the new mcr-4.4 and mcr-4.5 described here. Interestingly, the clonal
      group ST10-A (CH11-24) appears to be primarily responsible for the spread of mcr
      4. In summary, our results show that the pig industry is an important reservoir
      of colistin-resistant E. coli, carriers of other additional risk genes, such as
      blaESBL. These food-producing animals might be spreading a cocktail of multiple
      resistances, posing a worrisome threat to human health.

PMID- 29635008
TI  - Primary evidence of the mechanisms of action of HIV aspartyl peptidase inhibitors
      on Trypanosoma cruzi trypomastigote forms.
AB  - The development of HIV aspartyl peptidase inhibitors (HIV-PIs) and their
      introduction into AIDS therapy preceded a significant decrease in the incidence,
      morbidity and mortality of relevant protozoan co-infections. However, few data
      are available about how HIV-PIs act on pathogenic parasites, such as Trypanosoma
      cruzi, the etiological agent of Chagas disease. Therefore, the aim of the present
      work was to evaluate different physiological aspects of the treatment of the
      infective trypomastigote forms of T. cruzi with the HIV-PIs, nelfinavir and
      lopinavir. At the LD50/4 h doses, both HIV-PIs significantly reduced the
      trypomastigote size and markedly increased the granularity/complexity.
      Transmission electron microscopy analysis associated to biochemical assays
      permitted definition of the main HIV-PIs targets in the parasite. Lopinavir and
      nelfinavir induced (i) plasma membrane shedding, particularly in the flagellar
      region, which drastically affected parasite integrity; (ii) strong mitochondrial
      swelling with rare matrix fragmentation, which were linked to severely reduced
      hydrolytic activity of dehydrogenases and organelle membrane depolarization;
      (iii) increased generation of reactive oxygen species (ROS); (iv) dilation of
      both nuclear envelope (without DNA disruption) and endoplasmic reticulum (with
      formation of autophagosomes), and (v) accumulation of intracellular lipid
      droplets, revealing a typical lipid metabolism disorder. Collectively, our study
      demonstrated that nelfinavir and lopinavir target vital cellular structures of
      trypomastigotes, culminating in irreversible metabolic injuries that lead to T.
      cruzi death.

PMID- 29635009
TI  - The impact of CYP2B6 polymorphisms on the interactions of efavirenz with
      lumefantrine: Implications for paediatric antimalarial therapy.
AB  - Lumefantrine is a widely used antimalarial in children in sub-Saharan Africa and
      is predominantly metabolised by CYP3A4. The concomitant use of lumefantrine with
      the antiretroviral efavirenz, which is metabolised by CYP2B6 and is an inducer of
      CYP3A4, increases the risk of lumefantrine failure and can result in an increased
      recrudescence rate in HIV-infected children. This is further confounded by CYP2B6
      being highly polymorphic resulting in a 2-3 fold higher efavirenz plasma
      concentration in polymorphic subjects, which enhances the potential for an
      efavirenz-lumefantrine drug-drug interaction (DDI). This study developed a
      population-based PBPK model capable of predicting the impact of efavirenz
      mediated DDIs on lumefantrine pharmacokinetics in African paediatric population
      groups, which also considered the polymorphic nature of CYP2B6. The validated
      model demonstrated a significant difference in lumefantrine target day 7
      concentrations (Cd7) in the presence and absence of efavirenz and confirmed the
      capability of efavirenz to initiate this DDI. This was more apparent in the *6/*6
      compared to *1/*1 population group and resulted in a significantly lower (P <
      0.001) lumefantrine Cd7. A prospective change in dosing schedule from 3-days to 7
      days resulted in a greater number of *6/*6 subjects (28-57%) attaining the target
      Cd7 across age bands (0.25-13 years), with the greatest increase evident in the 1
      4 year old group (3-day: 1%; 7-day: 28%).

PMID- 29635010
TI  - Dose-reduction antiangiogenic curcumin-low molecular weight heparin nanodrugs for
      enhanced combinational antitumor therapy.
AB  - Curcumin (CUR) is a natural diketone with diverse bioactivities of inhibiting
      angiogenesis and tumor growth. However, its clinical application for cancer
      treatment was severely hindered by poor aqueous solubility and chemical
      instability. To overcome these drawbacks and achieve enhanced antitumor
      efficiency, low molecular weight heparin (LMWH) was conjugated to CUR via the one
      step esterification reaction to yield LMWH-CUR (LCU) nanodrugs with the size of
      180 nm, which exhibited enhanced accumulation within tumor site by EPR effect and
      long circulating capacity by LMWH hydrophilic shell. The solubility of conjugated
      CUR was increased to 0.12 mg/mL (equivalent of CUR) in comparison with 0.006
      mg/mL of free CUR. The bioactivities of CUR were guaranteed because of the
      improved stability of LCU nanodrugs in low pH condition. Moreover, the stronger
      anti-angiogenesis efficacy of LCU nanodrugs than LMWH monotherapy was also
      verified. Notably, at a rather low dose of equivalent LMWH (5 mg/kg) and CUR (0.3
      mg/kg), the tumor inhibition rate of LCU nanodrugs were much higher than that of
      LMWH (10 times) and LMWH plus CUR mixture (3.8 times) respectively, indicating
      its excellent in vivo antitumor efficacy. Overall, our study managed to obtain
      the novel nanodrugs with potent anti-angiogenesis and antitumor effects whereas
      avoiding tedious and complicated synthetic procedures. These results also
      suggested that LCU nanodrugs could be considered as a promising targeted delivery
      system for cancer treatment.

PMID- 29635011
TI  - The cysteine residue of glial fibrillary acidic protein is a critical target for
      lipoxidation and required for efficient network organization.
AB  - The type III intermediate filament protein glial fibrillary acidic protein (GFAP)
      contributes to the homeostasis of astrocytes, where it co-polymerizes with
      vimentin. Conversely, alterations in GFAP assembly or degradation cause
      intracellular aggregates linked to astrocyte dysfunction and neurological
      disease. Moreover, injury and inflammation elicit extensive GFAP organization and
      expression changes, which underline reactive gliosis. Here we have studied GFAP
      as a target for modification by electrophilic inflammatory mediators. We show
      that the GFAP cysteine, C294, is targeted by lipoxidation by cyclopentenone
      prostaglandins (cyPG) in vitro and in cells. Electrophilic modification of GFAP
      in cells leads to a striking filament rearrangement, with retraction from the
      cell periphery and juxtanuclear condensation in thick bundles. Importantly, the
      C294S mutant is resistant to cyPG addition and filament disruption, thus
      highlighting the critical role of this residue as a sensor of oxidative damage.
      However, GFAP C294S shows defective or delayed network formation in GFAP
      deficient cells, including SW13/cl.2 cells and GFAP- and vimentin-deficient
      primary astrocytes. Moreover, GFAP C294S does not effectively integrate with and
      even disrupts vimentin filaments in the short-term. Interestingly, short-spacer
      bifunctional cysteine crosslinking produces GFAP-vimentin heterodimers,
      suggesting that a certain proportion of cysteine residues from both proteins are
      spatially close. Collectively, these results support that the conserved cysteine
      residue in type III intermediate filament proteins serves as an electrophilic
      stress sensor and structural element. Therefore, oxidative modifications of this
      cysteine could contribute to GFAP disruption or aggregation in pathological
      situations associated with oxidative or electrophilic stress.

PMID- 29635012
TI  - A brief history of sex determination.
AB  - A fundamental biological question that has puzzled, but also fascinated mankind
      since antiquity is the one pertaining to the differences between sexes. Ancient
      cultures and mythologies poetically intended to explain the origin of the two
      sexes; philosophy offered insightful albeit occasionally paradoxical perceptions
      about men and women; and society as a whole put forward numerous intuitive
      observations about the traits that distinguish the two sexes. However, it was
      only through meticulous scientific research that began in the 16th century, and
      gradual technical improvements that followed over the next centuries, that the
      study of sex determination bore fruit. Here, we present a brief history of sex
      determination studies from ancient times until today, by selectively interviewing
      some of the milestones in the field. We complete our review by outlining some yet
      unanswered questions and proposing future experimental directions.

PMID- 29635013
TI  - Glyphosate based- herbicide exposure affects gut microbiota, anxiety and
      depression-like behaviors in mice.
AB  - Recently, a number of studies have demonstrated the profound relationship between
      gut microbiota (GM) alterations and behavioral changes. Glyphosate-based
      herbicides (GBH) have been shown to induce behavioral impairments, and it is
      possible that they mediate the effects through an altered GM. In this study, we
      investigated the toxic effects of GBH on GM and its subsequent effects on the
      neurobehavioral functions in mice following acute, subchronic and chronic
      exposure to 250 or 500 mg/kg/day. The effect of these acute and repeated
      treatments was assessed at the behavioral level using the open field, the
      elevated plus maze, the tail suspension and splash tests. Then, mice were
      sacrificed and the intestinal samples were collected for GM analysis. Subchronic
      and chronic exposure to GBH induced an increase of anxiety and depression-like
      behaviors. In addition, GBH significantly altered the GM composition in terms of
      relative abundance and phylogenic diversity of the key microbes. Indeed, it
      decreased more specifically, Corynebacterium, Firmicutes, Bacteroidetes and
      Lactobacillus in treated mice. These data reinforce the essential link between GM
      and GBH toxicity in mice and suggest that observed intestinal dysbiosis could
      increase the prevalence of neurobehavioral alterations.

PMID- 29635014
TI  - A comparative study on the sticking tendency of ibuprofen and ibuprofen sodium
      dihydrate to differently coated tablet punches.
AB  - In the present study, the sticking tendencies of ibuprofen and ibuprofen sodium
      dihydrate as model substances for a lipophilic and a hydrophilic sticky API to
      differently coated punches were investigated. Increased sticking was observed
      with the more polar ibuprofen sodium dihydrate than with the less polar
      ibuprofen. Interestingly, the anti-sticking performance of the punch coatings
      proved to be independent of the APIs' polarity. To understand this phenomenon,
      key properties of the punches were investigated. The AFM adhesive forces of both
      APIs to the differently coated punches as well as the surface free energies and
      the surface texture of these punches were determined. Separately evaluating these
      properties revealed only a partial correlation with the sticking observed during
      tableting. Consistent results with the tableting data could only be achieved if
      evaluating the surface texture in context with the chemical composition of the
      respective punch surfaces. It was concluded that each punch tip coating
      represents an entirely different system, which were described in detail as a
      result of the performed investigations. Particularly, chromium nitride-coated
      punches resulted in excellent anti-sticking performances because of a low
      chemical interaction with the APIs combined with a smooth and homogeneous surface
      texture.

PMID- 29635015
TI  - Ethnobotany of dioecious species: Traditional knowledge on dioecious plants in
      India.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: More than 15,000 angiosperm species are
      dioecious, i.e., having distinct male and female individual plants. The
      allocation of resources between male and female plants is different, and also
      variation in secondary metabolites and sex-biased herbivory is reported among
      dioecious plants. However, little is known about the ethnobotany of dioecious
      species and whether preferences exist for a specific gender, e.g., in food,
      medicine or timber. AIM OF THE STUDY: The aim of this study was: 1) to study
      whether Indian folk healers have preference for plant genders, and to document
      their knowledge and use of dioecious species; 2) to understand the concept of
      plant gender in Indian systems of medicine and folk medicine, and whether
      Ayurvedic literature includes any references to gender preference. MATERIALS AND
      METHODS: Lists of dioecious plants used in Indian systems of medicine and folk
      medicine were compiled. Ethnobotanical data was collected on perceptions and
      awareness of dioecious plants, and preferences of use for specific genders of
      dioecious species using semi-structured interviews with folk healers in Tamil
      Nadu, India. In addition, twenty Ayurvedic doctors were interviewed to gain
      insight into the concept of plant gender in Ayurveda. RESULTS: Indian systems of
      medicine contain 5-7% dioecious species, and this estimate is congruent with the
      number of dioecious species in flowering plants in general. Informants recognized
      the phenomenon of dioecy in 31 out of 40 species, and reported gender preferences
      for 13 species with respect to uses as timber, food and medicine. Among
      informants different plant traits such as plant size, fruit size, and visibility
      of fruits determines the perception of a plant being a male or female. Ayurvedic
      classical literature provides no straightforward evidence on gender preferences
      in preparation of medicines or treatment of illness, however it contains details
      about reproductive morphology and sexual differentiation of plants. CONCLUSIONS:
      A knowledge gap exists in ethnobotanical and ethnopharmacological literature on
      traditional knowledge of dioecious plants. From this explorative study it is
      evident that people have traditional knowledge on plant gender and preferential
      usages towards one gender. Based on this, we propose that researchers conducting
      ethnobotanical and ethnopharmacological studies should consider documenting
      traditional knowledge on sexual systems of plants, and test the existence of
      gender specific usages in their conceptual framework and hypothesis testing.
      Incorporating such concepts could provide new dimensions of scientific knowledge
      with potential implications to conservation biology, chemical ecology,
      ethnoecology and drug discovery.

PMID- 29635017
TI  - Impact of obesity on the efficacy of different biologic agents in inflammatory
      diseases: A systematic review and meta-analysis.
AB  - OBJECTIVE: Obesity is a worldwide epidemic and a growing body of evidence
      suggests that it may affect the body's response to biologic agents. We
      investigated the influence of obesity on the efficacy of different biologic
      agents used to treat inflammatory diseases. METHODS: Medline, EMBASE and the
      Cochrane Database were searched using relevant MeSH and keyword terms for obesity
      and bDMARDs. Articles were selected if they reported a clinical response in obese
      subjects relative to other BMI categories. Response and remission outcomes were
      assessed using meta-analysis and all other reported outcomes were summarized.
      RESULTS: Among the 3850 records retrieved, 24 articles met the inclusion
      criteria, including 10 on rheumatoid arthritis (RA), 4 on axial spondyloarthritis
      (axSpA), 4 on Crohn's disease (CD), 4 on psoriasis (Ps) and 2 on psoriasic
      arthritis (PsA). Four biological disease-modifying anti-rheumatic drugs (bDMARDs)
      - anti-TNF agents, T cell co-stimulation inhibitor (abatacept), IL-6 inhibitor
      (tocilizumab), and B-cell depletion therapy (rituximab) - were involved. The meta
      analysis showed that the odds to reach a good response or achieve remission were
      lower in obese (BMI>30kg/m2) than non-obese (BMI<=30kg/m2) patients who were
      treated with anti-TNF agents (good responder % in RA: OR 0.34, 95% CI 0.18-0.64;
      remission% in RA: OR 0.36, 95% CI 0.21-0.59; BASDAI50% in axSpA: OR 0.41, 95% CI
      0.21-0.83), but no significant difference between obese and non-obese was found
      in patients treated with abatacept (good responder % in RA: OR 0.75, 95% CI 0.42
      1.36; remission% in RA: OR 0.84, 95% CI 0.65-1.09) and tocilizumab (good
      responder % in RA: OR 1.08, 95% CI 0.44-2.63; remission% in RA: OR 0.91, 95% CI
      0.50-1.66). CONCLUSION: Obesity hampered the effect of anti-TNF agents, but not
      those of abatacept and tocilizumab, suggesting that a personalized treatment
      strategy should be considered for obese patients with inflammatory diseases.

PMID- 29635016
TI  - Brain microvascular endothelial-astrocyte cell responses following Japanese
      encephalitis virus infection in an in vitro human blood-brain barrier model.
AB  - Japanese encephalitis virus (JEV) remains a leading cause of encephalitis,
      globally, which continues to grow in importance despite the availability of
      vaccines. Viral entry into the brain can occur via the blood-brain barrier (BBB),
      and inflammation at the BBB is a common final pathway in many brain infections.
      However, the role of the BBB during JEV infection and the contribution of the
      endothelial and astrocytic cell inflammation in facilitating virus entry into the
      brain are incompletely understood. We established a BBB model using human brain
      endothelial cells (HBECs) and human astrocytes. HBECs are polarised, and
      therefore the model was inoculated by JEV from the apical side to simulate the in
      vivo situation. The effects of JEV on the BBB permeability and release of
      inflammatory mediators from both apical and basolateral sides, representing the
      blood and the brain side respectively were investigated. JEV infected HBECs with
      limited active virus production, before crossing the BBB and infecting
      astrocytes. Control of JEV production by HBECs was associated with a significant
      increase in permeability, and with elevation of many host mediators, including
      cytokines, chemokines, cellular adhesion molecules, and matrix metalloproteases.
      When compared to the controls, significantly higher amounts of mediators were
      released from the apical side as opposed to the basolateral side. The increased
      release of mediators over time also correlated with increased BBB permeability.
      Treatment with dexamethasone led to a significant reduction in the release of
      interleukin 6 (IL6), C-C motif chemokine ligand 5 (CCL5) and C-X-C motif
      chemokine ligand 10 (CXCL10) from the apical side with a reduction in BBB
      disruption and no change in JEV production. The results are consistent with the
      hypothesis that JEV infection of the BBB triggers the production of a range of
      host mediators from both endothelial cells and astrocytes, which control JEV
      production but disrupt BBB integrity thus allowing virus entry into the brain.
      Dexamethasone treatment controlled the host response and limited BBB disruption
      in the model without increasing JEV production, supporting a re-investigation of
      its use therapeutically.

PMID- 29635018
TI  - OBscure but not OBsolete: Perturbations of the frontal cortex in common between
      rodent olfactory bulbectomy model and major depression.
AB  - Olfactory bulbectomy (OBX) has been used as a model of depression over several
      decades. This model presupposes a mechanism that is still not proven in clinical
      depression. A wealth of clinical literature has focused on the derangements in
      frontal cortex (prefrontal, orbitofrontal and anterior cingulate cortices)
      associated with depression. In this comprehensive review, anatomical,
      electrophysiological and molecular sequelae of bulbectomy in the rodent frontal
      cortex are explored and compared with findings on brains of humans with major
      depression. Certain commonalities in neurobiological features of the perturbed
      frontal cortex in the bulbectomised rodent and the depressed human brain are
      evident. Also, meta-analysis reports on clinical studies on depressed patients
      provide prima facie evidence that perturbations in the frontal cortex are
      associated with major depression. Analysing the pattern of perturbations in the
      chemical neuroanatomy of the frontal cortex will contribute to understanding of
      the neurobiology of depression. Revisiting the OBX model of depression to examine
      these neurobiological changes in frontal cortex with contemporary imaging,
      proteomics, lipidomics, metabolomics and epigenomics technologies is proposed as
      an approach to enhance the translational value of this animal model to facilitate
      identification of targets and biomarkers for clinical depression.

PMID- 29635020
TI  - Role of the immune system in regeneration and its dynamic interplay with adult
      stem cells.
AB  - The immune system plays an indispensable role in the process of tissue
      regeneration following damage as well as during homeostasis. Inflammation and
      immune cell recruitment are signs of early onset injury. At the wound site,
      immune cells not only help to clear debris but also secrete numerous signalling
      molecules that induce appropriate cell proliferation and differentiation
      programmes essential for successful regeneration. However, the immune system does
      not always perform a complementary role in regeneration and several reports have
      suggested that increased inflammation can inhibit the regeneration process.
      Successful regeneration requires a balanced immune cell response, with the
      recruitment of accurately polarised immune cells in an appropriate quantity. The
      regulatory interactions of the immune system with regeneration are not
      unidirectional. Stem cells, as key players in regeneration, can also modulate the
      immune system in several ways to facilitate regeneration. In this review, we will
      focus on recent research demonstrating the key role of immune system in the
      regeneration process as well as the immunomodulatory effects of stem cells.
      Finally, we propose that research investigating the interplay between the immune
      system and stem cells within highly regenerating animals can benefit the
      identification of the key interactions and molecules required for successful
      regeneration.

PMID- 29635021
TI  - Ocular Metastasis of Bronchial Typical Carcinoid.

PMID- 29635022
TI  - Dynamic interneuron-principal cell interplay leads to a specific pattern of in
      vitro ictogenesis.
AB  - Ictal discharges induced by 4-aminopyridine in the in vitro rodent entorhinal
      cortex present with either low-voltage fast or sudden onset patterns. The role of
      interneurons in initiating low-voltage fast onset ictal discharges is well
      established but the processes leading to sudden onset ictal discharges remain
      unclear. We analysed here the participation of interneurons (n = 75) and
      principal cells (n = 13) in the sudden onset pattern by employing in vitro
      tetrode wire recordings in the entorhinal cortex of brain slices from Sprague
      Dawley rats. Ictal discharges emerged from a background of frequently occurring
      interictal spikes that were associated to a specific interneuron/principal cell
      interplay. High rates of interneuron firing occurred 12 ms before interictal
      spike onset while principal cells fired later during low interneuron firing. In
      contrast, the onset of sudden ictal discharges was characterized by increased
      firing from principal cells 627 ms before ictal onset whereas interneurons
      increased their firing rates 161 ms before ictal onset. Our data show that sudden
      onset ictogenesis is associated with frequently occurring interictal spikes
      resting on the interplay between interneurons and principal cells while ictal
      discharges stem from enhanced principal cell firing leading to increased
      interneuron activity. These findings indicate that specific patterns of
      interactions between interneurons and principal cells shape interictal and ictal
      discharges with sudden onset in the rodent entorhinal cortex. We propose that
      specific neuronal interactions lead to the generation of distinct onset patterns
      in focal epileptic disorders.

PMID- 29635023
TI  - Edaravone attenuates neuronal apoptosis in hypoxic-ischemic brain damage rat
      model via suppression of TRAIL signaling pathway.
AB  - BACKGROUND AND OBJECTIVES: Edaravone is a new type of oxygen free radical
      scavenger and able to attenuate various brain damage including hypoxic-ischemic
      brain damage (HIBD). This study was aimed at investigating the neuroprotective
      mechanism of edaravone in rat hypoxic-ischemic brain damage model and its
      correlation with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)
      signaling pathway. MATERIALS AND METHODS: 75 seven-day-old Sprague-Dawley
      neonatal rats were equally divided into three groups: sham-operated group (sham),
      HIBD group and HIBD rats injected with edaravone (HIBD + EDA) group. Neurological
      severity and space cognitive ability of rats in each group were evaluated using
      Longa neurological severity score and Morris water maze testing. TUNEL assay and
      flow cytometry were used to determine brain cell apoptosis. Western blot was used
      to estimate the expression level of death receptor-5 (DR5), Fas-associated
      protein with death domain (FADD), caspase 8, B-cell lymphoma-2 (Bcl-2) and Bcl-2
      associated X protein (Bax). In addition, immunofluorescence was performed to
      detect caspase 3. RESULTS: Edaravone reduced neurofunctional damage caused by
      HIBD and improved the cognitive capability of rats. The above experiment results
      suggested that edaravone could down-regulate the expression of active caspase 3
      protein, thereby relieving neuronal apoptosis. CONCLUSION: Taken together,
      edaravone could attenuate neuronal apoptosis in rat hypoxic-ischemic brain damage
      model via suppression of TRAIL signaling pathway, which also suggested that
      edaravone might be an effective therapeutic strategy for HIBD clinical treatment.

PMID- 29635024
TI  - The origins of the Psechridae: Web-building lycosoid spiders.
AB  - Psechrids are an enigmatic family of S.E. Asian spiders. This small family builds
      sheet webs and even orb webs, yet unlike other orb weavers, its putative
      relatives are largely cursorial lycosoids - a superfamily of approximately seven
      spider families related to wolf spiders. The orb web was invented at least twice:
      first in a very ancient event, and then second, within this clade of wolf-like
      spiders that reinvented this ability. Exactly how the spiders modified their
      silks, anatomy, and behaviors to accomplish this transition requires that we
      identify their precise evolutionary origins - yet, thus far, molecular
      phylogenies show poor support and considerable disagreement. Using phylogenomic
      methods based on whole body transcriptomes for psechrids and their putative
      relatives, we have recovered a well-supported phylogeny that places the
      Psechridae sister to the Ctenidae - a family of mostly cursorial habits but that,
      as with all psechrids, retains some cribellate species. Although this position
      reinforces the prevailing view that orb weaving in psechrids is largely a
      consequence of convergence, it is still possible that some components of this
      behavior are retained or resurrected in common with more distant true orb weaving
      ancestors.

PMID- 29635019
TI  - Planarian regeneration as a model of anatomical homeostasis: Recent progress in
      biophysical and computational approaches.
AB  - Planarian behavior, physiology, and pattern control offer profound lessons for
      regenerative medicine, evolutionary biology, morphogenetic engineering, robotics,
      and unconventional computation. Despite recent advances in the molecular genetics
      of stem cell differentiation, this model organism's remarkable anatomical
      homeostasis provokes us with truly fundamental puzzles about the origin of large
      scale shape and its relationship to the genome. In this review article, we first
      highlight several deep mysteries about planarian regeneration in the context of
      the current paradigm in this field. We then review recent progress in
      understanding of the physiological control of an endogenous, bioelectric pattern
      memory that guides regeneration, and how modulating this memory can permanently
      alter the flatworm's target morphology. Finally, we focus on computational
      approaches that complement reductive pathway analysis with synthetic, systems
      level understanding of morphological decision-making. We analyze existing models
      of planarian pattern control and highlight recent successes and remaining
      knowledge gaps in this interdisciplinary frontier field.

PMID- 29635025
TI  - A phylotranscriptomic backbone of the orb-weaving spider family Araneidae
      (Arachnida, Araneae) supported by multiple methodological approaches.
AB  - The orb-weaving spider family Araneidae is extremely diverse (>3100 spp.) and its
      members can be charismatic terrestrial arthropods, many of them recognizable by
      their iconic orbicular snare web, such as the common garden spiders. Despite
      considerable effort to better understand their backbone relationships based on
      multiple sources of data (morphological, behavioral and molecular), pervasive low
      support remains in recent studies. In addition, no overarching phylogeny of
      araneids is available to date, hampering further comparative work. In this study,
      we analyze the transcriptomes of 33 taxa, including 19 araneids - 12 of them new
      to this study - representing most of the core family lineages, to examine the
      relationships within the family using genomic-scale datasets resulting from
      various methodological treatments, namely ortholog selection and gene occupancy
      as a measure of matrix completion. Six matrices were constructed to assess these
      effects by varying orthology inference method and gene occupancy threshold.
      Orthology methods used are the benchmarking tool BUSCO and the tree-based method
      UPhO; three gene occupancy thresholds (45%, 65%, 85%) were used to assess the
      effect of missing data. Gene tree and species tree-based methods (including multi
      species coalescent and concatenation approaches, as well as maximum likelihood
      and Bayesian inference) were used totalling 17 analytical treatments. The
      monophyly of Araneidae and the placement of core araneid lineages were supported,
      together with some previously unsound backbone divergences; these include high
      support for Zygiellinae as the earliest diverging subfamily (followed by
      Nephilinae), the placement of Gasteracanthinae as sister group to Cyclosa and
      close relatives, and close relationships between the Araneus + Neoscona clade and
      Cyrtophorinae + Argiopinae clade. Incongruences were relegated to short branches
      in the clade comprising Cyclosa and its close relatives. We found congruence
      between most of the completed analyses, with minimal topological effects from
      occupancy/missing data and orthology assessment. The resulting number of genes by
      certain combinations of orthology and occupancy thresholds being analyzed had the
      greatest effect on the resulting trees, with anomalous outcomes recovered from
      analysis of lower numbers of genes.

PMID- 29635027
TI  - The emerging role of copper-64 radiopharmaceuticals as cancer theranostics.
AB  - Copper radionuclides are rapidly emerging as potential diagnostic and therapeutic
      tools in oncology, particularly 64Cu-radiopharmaceuticals for targeting
      neuroendocrine, prostate, and hypoxic tumors. Unexpectedly, experimental results
      are also revealing the impressive biological behavior of simple [64Cu2+] ions.
      For example, it has been demonstrated that administration of ionic [64Cu2+] in
      physiological solution allows the selective targeting of a variety of
      malignancies. These remarkable biological properties appear to be crucially
      linked to the natural role of copper ions in cell proliferation. Here, we review
      the current status of 64Cu-radiopharmaceuticals in molecular imaging and cancer
      therapy.

PMID- 29635028
TI  - Dynamic reorganization of TMS-evoked activity in subcortical stroke patients.
AB  - Since early days after stroke, the brain undergoes a complex reorganization to
      allow compensatory mechanisms that promote functional recovery. However, these
      mechanisms are still poorly understood and there is urgent need to identify
      neurophysiological markers of functional recovery after stroke. Here we aimed to
      track longitudinally the time-course of cortical reorganization by measuring for
      the first time EEG cortical activity evoked by TMS pulses in patients with
      subcortical stroke. Thirteen patients in the sub-acute phase of ischemic
      subcortical stroke with motor symptoms completed the longitudinal study, being
      evaluated within 20 days and after 40, 60 and 180 days after stroke onset. For
      each time-point, EEG cortical activity evoked by single TMS pulses was assessed
      over the motor and parietal cortex of the affected and unaffected hemisphere. We
      evaluated global TMS-evoked activity and TMS-evoked oscillations in different
      frequency bands. These measurements were paralleled with clinical and behavioral
      assessment. We found that motor cortical activity measured by TMS-EEG varied
      across time in the affected hemisphere. An increase of TMS-evoked activity was
      evident at 40 days after stroke onset. Moreover, stroke patients showed a
      significant increase in TMS-evoked alpha oscillations, as highlighted performing
      analysis in the time-frequency domain. Notably, these changes indicated that
      crucial mechanisms of cortical reorganization occur in this short-time window.
      These changes coincided with the clinical improvement. TMS-evoked alpha
      oscillatory activity recorded at baseline was associated to better functional
      recovery at 40 and 60 days' follow-up evaluations, suggesting that the power of
      the alpha rhythm can be considered a good predictor of motor recovery. This study
      demonstrates that cortical activity increases dynamically in the early phases of
      recovery after stroke in the affected hemisphere. These findings point to TMS
      evoked alpha oscillatory activity as a potential neurophysiological markers of
      stroke recovery and could be helpful to determine the temporal window in which
      neuromodulation should be potentially able to drive neuroplasticity in an
      effective functional direction.

PMID- 29635029
TI  - Microstructural imaging in the spinal cord and validation strategies.
AB  - In vivo histology using magnetic resonance imaging (MRI) is a newly emerging
      research field that aims to non-invasively characterize tissue microstructure.
      The implications of in vivo histology are many, from discovering novel biomarkers
      to studying human development, to providing tools for disease diagnosis and
      monitoring the effects of novel treatments on tissue. This review focuses on
      quantitative MRI (qMRI) techniques that are used to map spinal cord
      microstructure. Opening with a rationale for non-invasive imaging of the spinal
      cord, this article continues with a brief overview of the existing MRI techniques
      for axon and myelin imaging, followed by the specific challenges and potential
      solutions for acquiring and processing such data. The final part of this review
      focuses on histological validation, with suggested tissue preparation,
      acquisition and processing protocols for large-scale microscopy.

PMID- 29635026
TI  - NTM drug discovery: status, gaps and the way forward.
AB  - Incidence of pulmonary diseases caused by non-tuberculous mycobacteria (NTM),
      relatives of Mycobacterium tuberculosis, is increasing at an alarming rate,
      surpassing tuberculosis in many countries. Current chemotherapies require long
      treatment times and the clinical outcomes are often disappointing. There is an
      urgent medical need to discover and develop new, more-efficacious anti-NTM drugs.
      In this review, we summarize the current status of NTM drug development, and
      highlight knowledge gaps and scientific obstacles in NTM drug discovery. We
      propose strategies to reduce biological uncertainties and to begin to populate a
      NTM drug pipeline with attractive leads and drug candidates.

PMID- 29635031
TI  - Sleep loss disrupts Arc expression in dentate gyrus neurons.
AB  - Sleep loss affects many aspects of cognition, and memory consolidation processes
      occurring in the hippocampus seem particularly vulnerable to sleep loss. The
      immediate-early gene Arc plays an essential role in both synaptic plasticity and
      memory formation, and its expression is altered by sleep. Here, using a variety
      of techniques, we have characterized the effects of brief (3-h) periods of sleep
      vs. sleep deprivation (SD) on the expression of Arc mRNA and Arc protein in the
      mouse hippocampus and cortex. By comparing the relative abundance of mature Arc
      mRNA with unspliced pre-mRNA, we see evidence that during SD, increases in Arc
      across the cortex, but not hippocampus, reflect de novo transcription. Arc
      increases in the hippocampus during SD are not accompanied by changes in pre-mRNA
      levels, suggesting that increases in mRNA stability, not transcription, drives
      this change. Using in situ hybridization (together with behavioral observation to
      quantify sleep amounts), we find that in the dorsal hippocampus, SD minimally
      affects Arc mRNA expression, and decreases the number of dentate gyrus (DG)
      granule cells expressing Arc. This is in contrast to neighboring cortical areas,
      which show large increases in neuronal Arc expression after SD. Using
      immunohistochemistry, we find that Arc protein expression is also differentially
      affected in the cortex and DG with SD - while larger numbers of cortical neurons
      are Arc+, fewer DG granule cells are Arc+, relative to the same regions in
      sleeping mice. These data suggest that with regard to expression of plasticity
      regulating genes, sleep (and SD) can have differential effects in hippocampal and
      cortical areas. This may provide a clue regarding the susceptibility of
      performance on hippocampus-dependent tasks to deficits following even brief
      periods of sleep loss.

PMID- 29635032
TI  - Enriched expression of the ciliopathy gene Ick in cell proliferating regions of
      adult mice.
AB  - Cilia are essential for sensory and motile functions across species. In humans,
      ciliary dysfunction causes "ciliopathies", which show severe developmental
      abnormalities in various tissues. Several missense mutations in intestinal cell
      kinase (ICK) gene lead to endocrine-cerebro-osteodysplasia syndrome or short rib
      polydactyly syndrome, lethal recessive developmental ciliopathies. We and others
      previously reported that Ick-deficient mice exhibit neonatal lethality with
      developmental defects. Mechanistically, Ick regulates intraflagellar transport
      and cilia length at ciliary tips. Although Ick plays important roles during
      mammalian development, roles of Ick at the adult stage are poorly understood. In
      the current study, we investigated the Ick gene expression in adult mouse
      tissues. RT-PCR analysis showed that Ick is ubiquitously expressed, with
      enrichment in the retina, brain, lung, intestine, and reproductive system. In the
      adult brain, we found that Ick expression is enriched in the walls of the lateral
      ventricle, in the rostral migratory stream of the olfactory bulb, and in the
      subgranular zone of the hippocampal dentate gyrus by in situ hybridization
      analysis. We also observed that Ick staining pattern is similar to pachytene
      spermatocyte to spermatid markers in the mature testis and to an intestinal stem
      cell marker in the adult small intestine. These results suggest that Ick is
      expressed in proliferating regions in the adult mouse brain, testis, and
      intestine.

PMID- 29635030
TI  - Metaplasticity within the spinal cord: Evidence brain-derived neurotrophic factor
      (BDNF), tumor necrosis factor (TNF), and alterations in GABA function (ionic
      plasticity) modulate pain and the capacity to learn.
AB  - Evidence is reviewed that behavioral training and neural injury can engage
      metaplastic processes that regulate adaptive potential. This issue is explored
      within a model system that examines how training affects the capacity to learn
      within the lower (lumbosacral) spinal cord. Response-contingent (controllable)
      stimulation applied caudal to a spinal transection induces a behavioral
      modification indicative of learning. This behavioral change is not observed in
      animals that receive stimulation in an uncontrollable manner. Exposure to
      uncontrollable stimulation also engages a process that disables spinal learning
      for 24-48 h. Controllable stimulation has the opposite effect; it engages a
      process that enables learning and prevents/reverses the learning deficit induced
      by uncontrollable stimulation. These observations suggest that a learning episode
      can impact the capacity to learn in future situations, providing an example of
      behavioral metaplasticity. The protective/restorative effect of controllable
      stimulation has been linked to an up-regulation of brain-derived neurotrophic
      factor (BDNF). The disruption of learning has been linked to the sensitization of
      pain (nociceptive) circuits, which is enabled by a reduction in GABA-dependent
      inhibition. After spinal cord injury (SCI), the co-transporter (KCC2) that
      regulates the outward flow of Cl- is down-regulated. This causes the
      intracellular concentration of Cl- to increase, reducing (and potentially
      reversing) the inward flow of Cl- through the GABA-A receptor. The shift in GABA
      function (ionic plasticity) increases neural excitability caudal to injury and
      sets the stage for nociceptive sensitization. The injury-induced shift in KCC2 is
      related to the loss of descending serotonergic (5HT) fibers that regulate
      plasticity within the spinal cord dorsal horn through the 5HT-1A receptor.
      Evidence is presented that these alterations in spinal plasticity impact pain in
      a brain-dependent task (place conditioning). The findings suggest that ionic
      plasticity can affect learning potential, shifting a neural circuit from
      dampened/hard-wired to excitable/plastic.

PMID- 29635033
TI  - Treatments of tilapia (Oreochromis niloticus) using nitric oxide for quality
      improvement: Establishing a potential method for large-scale processing of farmed
      fish.
AB  - BACKGROUND: To find a succedaneum of present methods for slaughtering tilapia, we
      have demonstrated the influence of nitric oxide (NO) (saturated NO solution)
      through euthanasia before slaughter on the animal welfare and muscle color of
      tilapia. The results suggested that NO euthanasia significantly improved the
      animal welfare and muscle color. Besides, the investigation of NO postmortem
      treatment on the muscle color and color stability of tilapia fillets suggested
      that NO postmortem treatment not only improved the muscle color and color
      stability but also prolonged the shelf-life of tilapia fillets during the
      refrigerated storage. OBJECTIVE: To further investigate the effect of NO
      euthanasia on the quality of tilapia fillets and to estimate the safety of NO
      treatments (NO euthanasia and NO postmortem treatment) for the application of NO
      treatments in industrial manufacturing of tilapia and possibly of other fish
      species. METHODS: NO euthanasia was adopted in this study following a simulated
      fish processing line. HbNO and MbNO values were measured to clarify the mechanism
      and process of NO euthanasia. The blood parameters, muscle pH, rigor index, drip
      loss and total volatile basic nitrogen (TVB-N) values were measured to evaluate
      the quality of the fillets obtained from NO euthanized tilapia. Besides, the
      nitrate (NO3-) levels in the muscles after the refrigerated storage were detected
      to estimate the food safety of both NO euthanasia and NO postmortem treatment.
      RESULTS: Fillets obtained from the tilapia euthanized by NO showed a later
      reduction of muscle pH, a later onset of rigor mortis postmortem and less drip
      loss during the refrigerated storage than control. NO euthanasia caused less TVB
      N than control and prolonged the shelf life of tilapia fillets. Moreover, the NO3
      levels in the muscles of both NO euthanasia and NO postmortem treatment after
      the refrigerated storage were below the maximum permitted limit. CONCLUSION: Both
      the NO euthanasia and NO postmortem treatment are suitable for improving the
      quality of tilapia fillets and reducing the food safety threats, which may be
      valuable for industrial manufacturing of tilapia and may be applicable for other
      fish species.

PMID- 29635034
TI  - Altered corneal biomechanical properties in children with osteogenesis
      imperfecta.
AB  - PURPOSE: To evaluate biomechanical corneal properties in children with
      osteogenesis imperfecta (OI). METHODS: A prospective, observational, case-control
      study was conducted on children 6-19 years of age diagnosed with OI. Patients
      with OI and healthy control subjects underwent complete ophthalmic examinations.
      Additional tests included Ocular Response Analyzer (ORA) and ultrasonic
      pachymetry. Primary outcomes were central corneal thickness (CCT), corneal
      hysteresis (CH), and corneal resistance factor (CRF). Intraocular pressure (IOP)
      was measured directly by either iCare or Goldmann applanation and indirectly by
      the ORA (Goldmann-correlated and corneal-compensated IOP). Statistically
      significant differences between OI and control groups were determined using
      independent samples t test. RESULTS: A total of 10 of 18 OI cases (mean age, 13
      +/- 4.37 years; 8 males) and 30 controls (mean age, 12.76 +/- 2.62 years; 16
      males) were able to complete the corneal biomechanics and pachymetry testing.
      Children with OI had decreased CH (8.5 +/- 1.0 mm Hg vs 11.6 +/- 1.2 mm Hg [P <
      0.001]), CRF (9.0 +/- 1.9 mm Hg vs 11.5 +/- 1.5 [P < 0.001]) and CCT (449.8 +/-
      30.8 MUm vs 568 +/- 47.6 MUm [P < 0.001]) compared to controls. The corneal
      compensated IOP was significantly higher in OI cases (18.8 +/- 3.1 mm Hg) than in
      controls (15.0 +/- 1.6 mm Hg, P < 0.004), but there was no significant difference
      in Goldmann-correlated IOP (16.3 +/- 4.2 mm Hg vs 15.8 +/- 2.2 mm Hg).
      CONCLUSIONS: Collagen defects in OI alter corneal structure and biomechanics.
      Children with OI have decreased CH, CRF, and CCT, resulting in IOPs that are
      likely higher than measured by tonometry. These corneal alterations are present
      at a young age in OI. Affected individuals should be routinely screened for
      glaucoma and corneal pathologies.

PMID- 29635035
TI  - Reply.

PMID- 29635036
TI  - The wing base of the palaeodictyopteran genus Dunbaria Tillyard: Where are we
      now?
AB  - The structure of insect wing articulation is considered as reliable source of
      high level characters for phylogenetic analyses. However, the correct
      identification of homologous structures among the main groups of Pterygota is a
      hotly debated issue. Therefore, the reconstruction of the wing bases in Paleozoic
      extinct relatives is of great interest, but at the same time it should be treated
      with extreme caution due to distortions caused by taphonomic effects. The present
      study is focused on the wing base in Dunbaria (Spilapteridae). The articulation
      in Dunbaria quinquefasciata is mainly formed by a prominent upright axillary
      plate while the humeral plate is markedly reduced. Due to unique preservation of
      surface relief of the axillary plate, its composition shows a detailed pattern of
      three fused axillary sclerites and presumable position of the sclerite 3Ax. The
      obtained structures were compared among Spilapteridae and to other
      palaeodictyopterans Ostrava nigra (Homoiopteridae) and Namuroningxia elegans
      (Namuroningxiidae). The comparative study uncovered two patterns of 3Ax in
      Dunbaria and Namuroningxia, which correspond to their different suprafamilial
      classification. In contrast to previous studies these new results reveal the
      homologous structural elements in the wing base between Paleozoic
      Palaeodictyoptera and their extant relatives of Ephemeroptera, Odonata and
      Neoptera.

PMID- 29635037
TI  - Fine structure of the ladybird spermatozoa (Insecta, Coleoptera, Coccinellidae).
AB  - The sperm structure of several ladybird species belonging to different
      subfamilies of Coccinellidae was studied. Three main sperm types were clearly
      recognized, and were characterized by differences in acrosomal length, the
      presence of a dense coat around the acrosome, the length of the basal body, the
      amount of the centriole adjunct material, and the diameter of the mitochondrial
      derivatives. However, the whole group shares a pattern of the posterior sperm
      region uncommon for insects, in which the axoneme and other flagellar components
      are running parallel with the nucleus. As a general conclusion, this study has
      revealed an inconsistency between the sperm structure and the systematics of the
      group, indicating that the generic concepts within the group do not reflect a
      natural classification, a statement also shared by molecular studies.

PMID- 29635038
TI  - Functional analysis of N-terminal propeptide in the precursor of Vibrio
      vulnificus metalloprotease by using cell-free translational system.
AB  - Vibrio vulnificus is a human pathogen causing fatal septicemia with edematous and
      hemorrhagic skin damage. Among multiple virulence factors, an extracellular
      metalloprotease termed as V. vulnificus protease (VVP) is known to play a crucial
      role in eliciting the skin damage. The mature VVP (413 aa) is composed of two
      domains, the N-terminal core domain with proteolytic activity and the C-terminal
      domain mediates efficient attachment to protein substrates. However, VVP is
      produced as an inactive precursor (609 aa) with a signal peptide (24 aa) and
      propeptide (172 aa). In order to clarify the function of propeptide, a series of
      DNA fragments encoding the VVP precursor and its various domains were designed
      and the proteins were expressed in vitro by using cell-free translational system.
      The results indicated that the propeptide might function as an intramolecular
      chaperon to promote the proper folding of both N-terminal and C-terminal domains.
      The obtained results also suggest that the propeptide, itself was unstable and
      thus digested easily by the enzymes present in cell lysate used for cell-free
      system. Additionally, the C-terminal domain in VVP found to inhibit the folding
      of the N-terminal domain in absence of propeptide.

PMID- 29635039
TI  - Prednisolone treatment reduces the osteogenic effects of loading in mice.
AB  - Glucocorticoid treatment, a major cause of drug-induced osteoporosis and
      fractures, is widely used to treat inflammatory conditions and diseases. By
      contrast, mechanical loading increases bone mass and decreases fracture risk.
      With these relationships in mind, we investigated whether mechanical loading
      interacts with GC treatment in bone. Three-month-old female C57BL/6 mice were
      treated with high-dose prednisolone (15 mg/60 day pellets/mouse) or vehicle for
      two weeks. During the treatment, right tibiae were subjected to short periods of
      cyclic compressive loading three times weekly, while left tibiae were used as
      physiologically loaded controls. The bones were analyzed using peripheral
      quantitative computed tomography, histomorphometry, real-time PCR, three-point
      bending and Fourier transform infrared micro-spectroscopy. Loading alone
      increased trabecular volumetric bone mineral density (vBMD), cortical thickness,
      cortical area, osteoblast-associated gene expression, osteocyte- and osteoclast
      number, and bone strength. Prednisolone alone decreased cortical area and
      thickness and osteoblast-associated gene expression. Importantly, prednisolone
      treatment decreased the load-induced increase in trabecular vBMD by 57% (p <
      0.001) and expression of osteoblast-associated genes, while completely abolishing
      the load-induced increase in cortical area, cortical thickness, number of
      osteocytes and osteoclasts, and bone strength. When combined, loading and
      prednisolone decreased the collagen content. In conclusion, high-dose
      prednisolone treatment strongly inhibits the loading-induced increase in
      trabecular BMD, and abolishes the loading-induced increase in cortical bone mass.
      This phenomenon could be due to prednisolone inhibition of osteoblast
      differentiation and function.

PMID- 29635040
TI  - Dimer-monomer equilibrium of human HSP27 is influenced by the in-cell
      macromolecular crowding environment and is controlled by fatty acids and heat.
AB  - Small heat shock protein 27 (HSP27) is an essential element of the proteostasis
      network in human cells. The HSP27 monomer coexists with the dimer, which can bind
      unfolded client proteins. Here, we evaluated the in-cell dimer-monomer
      equilibrium and its relevance to the binding of client proteins in a normal human
      vascular endothelial cell line. When cells were treated with a membrane-permeable
      crosslinker, the protein existed primarily as a free monomer (27 kDa) with a
      markedly smaller percentage of dimer (54 kDa), hetero-conjugates, and minor smear
      like bands. When the protein was crosslinked in a cell-free lysate, two of the
      hetero-conjugates that were crosslinked in live cells were also detected, but the
      dimer and other complexes were absent. However, when cells were pretreated with
      fatty acid (FA) and/or heat (42.5  degrees C), dissociation of the dimer was
      selectively prevented and two types of covalently linked dimers were increased.
      These changes occurred most prominently in cells treated with docosahexaenoic
      acid (DHA) and heat, which appeared to intensify the heat resistance of the cell.
      Both the formation of covalently linked dimers and heat resistance were prevented
      by N-acetylcysteine. By contrast, nearly all of the free monomers in the lysate
      converted to disulfide bond-linked dimers by a simple, long incubation at 4 
      degrees C. These results strongly suggest that the monomer-dimer equilibrium of
      HSP27 was inversed between the in-cell and cell-free systems. Temperature- and
      amphiphile-regulated dimerization was restricted probably due to the low
      hydration of the in-cell crowding environment.

PMID- 29635041
TI  - The Biocompatibility of Nanoporous Acupuncture Needles.
AB  - We investigate the biocompatibility of a new class of acupuncture needles that
      possess a hierarchical nano/microscale porous surface topology, referred to as
      porous acupuncture needles (PAN). The PAN is synthesized via a facile
      electrochemical anodization technique by which a surface area approximately 20
      times greater than a conventional acupuncture needle, of approximately the same
      diameter, is obtained. PAN biocompatibility is evaluated using a variety of
      standard tests, with results indicating that the PAN can safely be used within
      therapeutic practice.

PMID- 29635042
TI  - Effect of Ca2+ on the redox potential of heme a in cytochrome c oxidase.
AB  - Subunit I of cytochrome c oxidase (CcO) from mitochondria and many bacteria
      contains a cation binding site (CBS) located at the outer positively charged
      aqueous phase not far from heme a. Binding of Ca2+ with the CBS in bovine CcO
      inhibits activity of the enzyme 2-3 -fold [Vygodina, T., Kirichenko, A. &
      Konstantinov A.A. (2013) Direct Regulation of Cytochrome c Oxidase by Calcium
      Ions, PLoS One.8 e74436]. Here we show that binding of Ca2+ at CBS of bovine CcO
      shifts Em of heme a to the positive by 15-20 mV. Na+ ions that bind to the same
      site and compete with Ca2+ do not affect Em of heme a and also prevent and
      reverse the effect of Ca2+. No effect of Ca2+ or EGTA is observed on Em of heme a
      with the wild type bacterial oxidases from R.sphaeroides or P.denitrificans that
      contain tightly-bound calcium at the site. In the D477A mutant CcO from P.
      denitrificans that binds Ca2+ reversibly like the mitochondrial CcO, calcium
      shifts redox titration curve of heme a to the positive by ~35-50 mV that is in
      good agreement with the results of electrostatic calculations; however, as shown
      earlier, it does not inhibit CcO activity of the mutant enzyme. Therefore the
      data do not support the proposal that the inhibitory effect of Ca2+ on CcO
      activity may be explained by the Ca2+-induced shift of Em of heme a. Rather, Ca2+
      retards electron transfer by inhibition of charge dislocation in the exit part of
      the proton channel H in mammalian CcO, that is absent in the bacterial oxidases.

PMID- 29635043
TI  - Unique nuclear localization of Nile tilapia (Oreochromis niloticus) Neu4
      sialidase is regulated by nuclear transport receptor importin alpha/beta.
AB  - Sialidase catalyzes the removal of sialic acids from glycoconjugates. Different
      from Neu1 and Neu3 sialidases, Neu4 enzymatic properties such as substrate
      specificity and subcellular localization are not well-conserved among
      vertebrates. In fish only zebrafish and medaka neu4 genes have been cloned and
      their polypeptides have been characterized so far. Thus, characterization of Neu4
      from other fish species is necessary to evaluate Neu4 physiological functions.
      Here, Nile tilapia was chosen for the characterization of Neu4 polypeptide
      considering that it is one of the major cultured fish all over the world and that
      its genomic sequences are now available. Coding DNA sequence of tilapia Neu4 was
      identified as 1,497 bp and its recombinant protein showed broad substrate
      specificity and optimal sialidase enzyme activity pH at 4.0. Neu4 activity was
      sustained even in neutral and alkali pH. Interestingly, immunofluorescence
      analysis revealed that major subcellular localization of tilapia Neu4 was
      nuclear, quite distinct from zebrafish (ER) and medaka Neu4 (lysosome).
      Bioinformatic analysis showed the existence of putative nuclear localization
      signal (NLS) in tilapia Neu4. In general, it is known that importin families bind
      to several proteins via NLS and transfer them into nucleus. Therefore, to
      determine the involvement of putative NLS in Neu4 nuclear localization, Neu4
      mutant deleting NLS was constructed and expressed in cultured cells. As a result,
      NLS deletion significantly diminished the nuclear localization. Furthermore,
      treatment of importazole, interrupter of binding importin beta and RanGTP,
      significantly suppressed Neu4 nuclear localization. In summary, tilapia Neu4 is a
      unique sialidase localized at nucleus and its transport system into nucleus is
      regulated by importin.

PMID- 29635044
TI  - Chikungunya virus inhibition by peptidomimetic inhibitors targeting virus
      specific cysteine protease.
AB  - Chikungunya virus (CHIKV), a mosquito-borne pathogenic virus that reemerged and
      caused epidemic in the Indian Ocean island of La Reunion, is a potential public
      health threat. Currently there is no antiviral drug or vaccine commercially
      available for the treatment of chikungunya fever, which necessitates the urge for
      an effective antiviral therapy for chikungunya treatment. In the present study, a
      FRET based protease assay was used to analyze the proteolytic activity of
      chikungunya nsP2 protease (CHIKV nsP2pro) - an essential viral enzyme, with
      fluorogenic substrate peptide. This protease assay was used to assess the
      inhibitory activity of Pep-I (MMsINC(r) database ID MMs03131094) and Pep-II
      (MMsINC(r) database ID MMs03927237), peptidomimetic compounds identified in a
      previous study by our group. Both compounds inhibited CHIKV nsP2pro with half
      maximal inhibition concentration (IC50) values of ~34 MUM and ~42 MUM,
      respectively. Kinetic studies showed that the inhibition constant (Ki) value is
      33.34 +/- 2.53 MUM for Pep-I and 45.89 +/- 4.38 MUM for Pep-II. Additionally,
      these two compounds significantly inhibited CHIKV replication in BHK-21 cells at
      concentrations much lower than their cytotoxic concentrations. Intriguingly,
      these compounds did not show inhibitory effect on Sindbis virus. This suggests
      that Pep-I and Pep-II compounds identified as CHIKV nsP2 substrate
      peptidomimetics, specifically inhibit CHIKV replication.

PMID- 29635045
TI  - Implantation loss induced by ethanolamine in the rat is ameliorated by a choline
      supplemented diet.
AB  - Ethanolamine (EA) reduced implantation success in a two-generation reproduction
      toxicity study; the aim of this work was to explore the underlying basis for this
      response. When administered to pregnant rats during gestation days (GD) 1-3, 4-5,
      or 6-7, EA had no effect upon implantation success. In a second experiment, EA
      was administered either in the diet or by oral gavage from two weeks prior to
      mating through to GD 8. Parallel groups also received a diet supplemented with
      choline. In the absence of supplementary choline, EA induced early resorptions,
      statistically significant only when administered in the diet. A slight reduction
      in implantation success was ameliorated by supplementary choline. We conclude
      that implantation is affected by EA only when exposure starts before mating; that
      dietary administration is more effective than gavage dosing; and that
      interference with choline homeostasis may play a role in the aetiology of this
      lesion.

PMID- 29635046
TI  - Effects of Bisphenol-A on proliferation and expression of genes related to
      synthesis of polyamines, interferon tau and insulin-like growth factor 2 by ovine
      trophectoderm cells.
AB  - This study evaluated the effects of bisphenol A (BPA) on proliferation of ovine
      trophectoderm (oTr1) cells, as well as expression of genes for transport of
      arginine and synthesis of polyamines. BPA reduced proliferation of oTr1 cells at
      concentrations of 1 * 10-6, 1 * 10-5, 1 * 10-4 M compared to concentrations of 0,
      1 * 10-9, and 1 * 10-8 M at 24 and 96 h of culture. Lower concentrations of BPA
      significantly increased expression of mRNAs for agmatinase (AGMAT), arginine
      decarboxylase (ADC), ornithine decarboxylase (ODC1) and solute carrier family 7
      member 1 (SLC7A1). Similarly, synthesis of polyamines by oTr1 cells was greatest
      at lower concentrations of BPA and decreased as the dose of BPA increased.
      Expression of mRNAs for interferon tau (IFNT) and insulin-like growth factor 2
      (IGF2) by oTr1 cells was greater than for controls at 1 * 10-9 M BPA. Overall,
      the effects of BPA on proliferation and gene expression by oTr1 cells were highly
      dose-dependent.

PMID- 29635047
TI  - The impact of confounder selection in propensity scores when applied to
      prospective cohort studies in pregnancy.
AB  - Our work was motivated by small cohort studies on the risk of birth defects in
      infants born to pregnant women exposed to medications. We controlled for
      confounding using propensity scores (PS). The extremely rare events setting
      renders the matching or stratification infeasible. In addition, the PS itself may
      be formed via different approaches to select confounders from a relatively long
      list of potential confounders. We carried out simulation experiments to compare
      different combinations of approaches: IPW or regression adjustment, with 1)
      including all potential confounders without selection, 2) selection based on
      univariate association between the candidate variable and the outcome, 3)
      selection based on change in effects (CIE). The simulation showed that IPW
      without selection leads to extremely large variances in the estimated odds ratio,
      which help to explain the empirical data analysis results that we had observed.

PMID- 29635048
TI  - Expression of kappa opioid receptors in developing rat brain - Implications for
      perinatal buprenorphine exposure.
AB  - Buprenorphine, a mu opioid receptor partial agonist and kappa opioid receptor
      (KOR) antagonist, is an emerging therapeutic agent for maternal opioid dependence
      in pregnancy and neonatal abstinence syndrome. However, the endogenous opioid
      system plays a critical role in modulating neurodevelopment and perinatal
      buprenorphine exposure may detrimentally influence this. To identify aspects of
      neurodevelopment vulnerable to perinatal buprenorphine exposure, we defined KOR
      protein expression and its cellular associations in normal rat brain from
      embryonic day 16 to postnatal day 23 with double-labelling immunohistochemistry.
      KOR was expressed on neural stem and progenitor cells (NSPCs), choroid plexus
      epithelium, subpopulations of cortical neurones and oligodendrocytes, and NSPCs
      and subpopulations of neurones in postnatal hippocampus. These distinct patterns
      of KOR expression suggest several pathways vulnerable to perinatal buprenorphine
      exposure, including proliferation, neurogenesis and neurotransmission. We thus
      suggest the cautious use of buprenorphine in both mothers and infants until its
      impact on neurodevelopment is better defined.

PMID- 29635049
TI  - Effects of maternal subclinical hypothyroidism on amniotic fluid cells oxidative
      status.
AB  - In this study, we researched the effects of maternal subclinical hypothyroidism
      on the amniotic fluid cells oxidative metabolism during the first trimester of
      pregnancy. Oxidative stress and damage biomarkers were assayed in the amniotic
      fluid cells of healthy and pregnant women with subclinical hypothyroidism.
      Obtained results show that amniotic fluid cells of pregnant women with
      subclinical hypothyroidism have significantly higher concentrations of oxidative
      stress biomarkers (superoxide anion, nitric oxide, peroxynitrite) and oxidative
      damage (lipid peroxide and micronuclei frequency), but lower concentrations of
      hydrogen peroxide and oxidized glutathione in comparison to healthy pregnant
      women. We also showed that oxidative stress biomarkers were positively correlated
      with micronuclei frequency and lipid peroxide concentration in amniotic fluid
      cells of pregnant women with subclinical hypothyroidism. The present study
      provides the first evidence for prooxidative effects of maternal subclinical
      hypothyroidism on the fetus obtained by the estimating oxidative metabolism in
      the amniotic fluid cells.

PMID- 29635050
TI  - Enhancing using glucose encapsulation, the efficacy of CdO NPs against multi-drug
      resistant Escherichia coli.
AB  - In this study, monodispersed, highly biocompatible and substantially stable
      glucose encapsulated CdO nanoparticles (G-CdO NPs) of uniform sizes were
      synthesized using a sol-gel route. In addition, naked CdO (n-CdO) NPs without any
      capping or surface functionalization were synthesized using the same method.
      These NPs were uniformly dispersed in an aqueous solution. The synthesis of G-CdO
      and n-CdO NP was confirmed by UV-Vis spectroscopy, transmission electron
      microscopy (TEM), zeta potential, and dynamic light scattering analyses. The
      average size of G-CdO and n-CdO NP was found to be 17+/-1and 27 +/- 1 nm, under
      TEM, respectively. X-ray diffraction analysis of G-CdO and n-CdO NPs confirmed
      their sizes to be 18.83 and 28.41 nm, respectively, and revealed their cubic
      crystal structures with no impurity. The surface functionalization of G-CdO NPs
      with glucose was confirmed by Nuclear Magnetic Resonance and Fourier-transform
      infrared spectroscopy analyses. As per our knowledge, this is the first report to
      investigate the potencies of G-CdO and n-CdO NPs against gram-negative and gram
      positive multi-drug resistant (MDR) bacteria. The minimum inhibitory
      concentrations of G-CdO and n-CdO NPs were6.42 and 16.29 MUg/ml, respectively,
      against Escherichia coli (NCIM 2571-MDR), whereas 7.5 MUg/ml & 11.6 MUg/ml,
      respectively against S. aureus (NCIM- 2079) as determined by the double dilution
      method. The minimum bactericidal concentration was determined at the
      concentration for which no growth was observed. TEM analysis of E. coli cells
      treated with G-CdO NPs revealed cell shrinkage and degraded cell membranes, while
      the cell surfaces of untreated viable cells were smooth.

PMID- 29635052
TI  - Mechanism of pattern recognition receptors (PRRs) and host pathogen interplay in
      bovine mastitis.
AB  - Bacterial infection in the mammary gland parenchyma induces local and
      subsequently systemic inflammation that results in a complex disease. Mastitis in
      bovine is the result of various factors which function together. This review is
      aimed to analyze the factors involved in the pathogenesis of common bacterial
      species for bovine mastitis. The bacterial growth patterns, signaling pathway and
      the pathogen-associated molecular patterns (PAMPs) which activate immune
      responses is discussed. Clear differences in bacterial infection pattern are
      shown between bacterial species and illustrated TLRs, NLRs and RLGs molecular
      mechanism for the initiation of intramammary infection. The underlying reasons
      for the differences and the resulting host response are analyzed. Understandings
      of the mechanisms that activate and regulate these responses are central to the
      development of efficient anticipatory and treatment management. The knowledge of
      bovine mammary gland to common mastitis causing pathogens with possible immune
      mechanism could be a new conceptual understanding for the prospect of mastitis
      control program.

PMID- 29635051
TI  - Analysis of two quorum sensing-deficient isolates of Pseudomonas aeruginosa.
AB  - Three strains of Pseudomonas aeruginosa were isolated: wild-type (WT, NO4) showed
      normal quorum sensing (QS), whereas QSD3 and QSD7 were QS-deficient (QSD)
      containing limited N-butyryl homoserine lactone (C4-HSL). The autoinducer
      activity produced by NO4 was found to be at least 50-fold higher than those by
      the QSD3 and the QSD7 strains. The QSDs produced lower levels of phenazine
      compounds (pyocyanin), siderophores (pyoverdine) and biosurfactants
      (rhamnolipids) than NO4. Therefore, the swarming motility and the swimming
      motility of the QSD3 and the QSD7 strains also decreased. Treatment with
      exogenous C4-HSL completely restored rhamnolipid production in both QSDs,
      suggesting that the biosynthesis of C4-HSL is defective. However, the biofilm
      production of the QSDs reached much higher levels than those of wild-types (NO4
      and P. aeruginosa PAO1). And both QSD strains were more resistant than wild-type
      cell (NO4) against kanamycin and tobramycin. The RpoS gene, which function is
      related with QS, is point-nonsense mutated in QSD3 strain. But eleven QS-related
      genes in QSD3 were not mutated, compared to those of PAO1, which carries intact
      QS genes and is used as a positive control. This study is helpful in the
      development of novel approaches in the treatment of P. aeruginosa infections.

PMID- 29635053
TI  - Resiquimod enhances mucosal and systemic immunity against avian infectious
      bronchitis virus vaccine in the chicken.
AB  - Adjuvant enhancing mucosal immune response is preferred in controlling many
      pathogens at the portal of entry. Earlier, we reported that a toll-like-receptor
      7 (TLR7) agonist, resiquimod (R-848), stimulated the systemic immunity when
      adjuvanted with the inactivated Newcastle disease virus vaccine in the chicken.
      Here, we report the effect of R-848 when adjuvanted with live or inactivated
      avian infectious bronchitis virus (IBV) vaccines with special emphasis on mucosal
      immunity. Specific pathogen free (SPF) chicks (n = 60) were equally divided into
      six groups at two weeks of age and immunized with either inactivated or live IBV
      vaccine adjuvanted with or without R-848. Groups that received either PBS or R
      848 served as control. A booster was given on 14 days post-immunization (dpi). R
      848 enhanced the antigen specific humoral and cellular immune responses when co
      administered with the vaccines as evidenced by an increase in the antibody titre
      in ELISA and stimulation index in lymphocyte transformation test (LTT) till 35
      dpi and increased proportion of CD4+ and CD8+ T cells on 21 dpi in the flow
      cytometry. Interestingly, it potentiated the IgA responses in the tear and
      intestinal secretions when used with both live and inactivated IBV vaccines. The
      combination of IBV vaccine with R-848 significantly up-regulated the transforming
      growth factor beta 4 (TGFbeta4) transcripts in the peripheral blood mononuclear
      cells (PBMCs) than that of the respective vaccine per se. An enhanced secretory
      IgA response is likely due to the up-regulation of TGFbeta4, which is responsible
      for class switching to IgA. In conclusion, co-administration of R-848 with
      inactivated or live IBV vaccine enhanced the systemic as well as mucosal immune
      responses in the chicken.

PMID- 29635054
TI  - Current regulatory requirements and practical approaches for stability analysis
      of pharmaceutical products: A comprehensive review.
AB  - Different regulatory guidelines recommend establishing stability profile of
      pharmaceuticals at the time of drug development. The expiry date, retesting
      period and storage conditions of active drugs or products are established through
      stability analysis. Several regulatory guidelines exist for stability testing of
      pharmaceuticals. Mostly, ICH stability guidelines are followed in practice. This
      guideline recommends to validate stability indicating method using forced
      degradation samples that contains all possible degradation impurities. ICH
      guidelines provide general recommendations for inclusion of stability indicating
      parameters in a stability testing protocol. However, those guidelines do not
      provide specific requirements and experimental methodology to be followed for
      stability studies. Due to this gap, often confusion arises in the scientific
      community in designing stability testing protocol. Therefore, significant
      variations are observed in reported literature in selection of stability
      indicating parameters. Procedural dissimilarity amongst reported stability
      studies is also evident. This review discusses the regulatory guidelines and
      procedures to follow in performing stability testing of pharmaceuticals. Scope of
      this review also includes recommendations on practical approaches for designing
      stability testing protocol to fulfill current regulatory requirements for drug
      substances and their formulations.

PMID- 29635055
TI  - Polysorbate 20 alters the oral bioavailability of etoposide in wild type and
      mdr1a deficient Sprague-Dawley rats.
AB  - The aim of the present work was to investigate the ability of nonionic
      surfactants to increase the oral absorption of the P-glycoprotein substrate
      etoposide in vitro and in vivo. Intestinal absorption was investigated by
      studying bidirectional permeability of etoposide across filter-grown Caco-2 and
      MDCKII MDR1 cell monolayers. The oral absorption of etoposide was investigated in
      wild type (WT) and mdr1a deficient (KO) Sprague-Dawley rats. In cell cultures,
      polysorbate 20 (PS20) decreased P-glycoprotein mediated efflux of etoposide. When
      PS20 and etoposide were co-administered to WT rats, the oral absorption of
      etoposide increased significantly in the presence of 5 and 25% (v/v) PS20.
      However, in KO rats, the exposure of etoposide after oral co-administration with
      5% PS20 was similar to control. Unexpectedly, co-administration of etoposide with
      25% PS20 significantly reduced the absorption fraction of etoposide in mdr1a KO
      rats. In vitro dialysis studies performed on PS20-containing etoposide solutions
      suggested that the reduced bioavailability may be due to etoposide retention in
      PS20 micelles and/or through increased viscosity. In conclusion, PS20 increases
      oral bioavailability of etoposide through inhibition of P-glycoprotein. However,
      the use of the excipient may be challenged by etoposide retention at higher
      concentrations.

PMID- 29635056
TI  - Mass Median Plume Angle: A novel approach to characterize plume geometry in
      solution based pMDIs.
AB  - High-speed laser imaging (HSLI) is the preferred technique to characterize the
      geometry of the plume in pressurized metered dose inhalers (pMDIs). However,
      current methods do not allow for simulation of inhalation airflow and do not use
      drug mass quantification to determine plume angles. To address these limitations,
      a Plume Induction Port Evaluator (PIPE) was designed to characterize the plume
      geometry based on mass deposition patterns. The method is easily adaptable to
      current pMDI characterization methodologies, uses similar calculations methods,
      and can be used under airflow. The effect of airflow and formulation on the plume
      geometry were evaluated using PIPE and HSLI. Deposition patterns in PIPE were
      highly reproducible and log-normal distributed. Mass Median Plume Angle (MMPA)
      was a new characterization parameter to describe the effective angle of the
      droplets deposited in the induction port. Plume angles determined by mass showed
      a significant decrease in size as ethanol increases which correlates to the
      decrease on vapor pressure in the formulation. Additionally, airflow
      significantly decreased the angle of the plumes when cascade impactor was
      operated under flow. PIPE is an alternative to laser-based characterization
      methods to evaluate the plume angle of pMDIs based on reliable drug
      quantification while simulating patient inhalation.

PMID- 29635057
TI  - Long chain fatty acid conjugation remarkably decreases the aggregation induced
      toxicity of Amphotericin B.
AB  - Amphotericin B is an antimicrobial membrane-acting drug used in the treatment of
      systemic fungal infections. However, the clinical utility of AmB is often low as
      a result of (i) dose-limiting toxicity which is closely associated with its
      aggregation wherein the selectivity for its target i.e. ergosterol in fungal
      membranes is diminished and (ii) limited oral bioavailablity. The latter is
      attributed to the unfavorable physicochemical properties of the AmB e.g., low
      solubility, gastrointestinal instability, and poor intestinal permeability. The
      hypothesis of present work was that by applying a lipid conjugation approach the
      aggregation induced toxicity of AmB vis-a-vis permeability can be overcome. From
      the array of fatty acids, the oleic acid (OA) was selected for conjugation due to
      its great impact on increasing the Caco-2 permeability of AmB. AmB-OA conjugate
      was synthesized using standard carbodiimide chemistry and characterized
      thoroughly. Due to the reported strong correlation between the self-aggregation
      of AmB and toxicity, the aggregation behavior of AmB and AmB-OA was studied by in
      silico modeling and confirmed experimentally. In vitro hemolytic studies and
      viability assays in kidney cells (HEK 293 cells) suggested that AmB in aggregated
      was state highly toxic but not AmB-OA. In silico modeling suggested possible
      aggregation conformation of AmB-OA dimers that retains the selectivity for
      cholesterol even in aggregated state when embedded in in silico generated lipid
      bilayers. The results were further confirmed by assessing the interactions of
      monomeric and aggregated state of AmB and AmB-OA with that of cholesterol and
      ergosterol containing liposomes employing circular dichroism spectroscopy. The
      findings were subsequently corroborated by in vivo nephrotoxicity studies. To
      conclude, the lipid conjugation approach may be a promising strategy for reducing
      the dose-limiting toxicity of AmB.

PMID- 29635058
TI  - Elemental impurities in lipsticks: Results from a survey of the Portuguese and
      Brazilian markets.
AB  - For safety reasons, European regulations prohibit the use of a long list of
      metal(loid)s as ingredients of cosmetic products. However, their presence as
      impurities in finished products is virtually unavoidable, even under GMP
      conditions. This study aimed at determining the elemental profile of lipsticks
      available in the Portuguese and Brazilian markets. A total of 96 lipsticks were
      purchased in Brazil (n = 53; 9 brands) and Portugal (n = 43; 7 brands) and the
      content of 44 elements was determined. Results ranged from <1 MUg/g to several
      tens of MUg/g (e.g., Sn, Mn, Zn). Significant differences were found between
      Portuguese and Brazilian products for several elements, particularly for Pb. For
      the elements of major toxicological concern (Pb, Cd, As, Sb, Hg), mean values
      were always below the current limits set by the German competent authority.
      However, a significant percentage of exceedances were observed for Pb (24%) and
      Cd (21%). A safety assessment was carried out for the toxicologically relevant
      elements. Results showed that, except for Pb, the systemic exposure resulting
      from lipstick use represents less than 0.2% (ca. 3% for Pb) of the respective
      permitted daily exposure even in the worst-case scenario (i.e., ingestion of the
      total amount of product applied).

PMID- 29635059
TI  - An innovative investigative approach to characterize the effects observed in a
      combined fertility study in male and female rats.
AB  - This paper describes the characterization of male- and female-mediated effects in
      a standard ICH rat fertility and early embryonic development study with a
      discontinued clinical small molecule. In the standard study, the test item had no
      effect on the number of treated females becoming pregnant, but litter sizes were
      reduced at the high dose level. In the treated male rats, increased incidences of
      abnormal sperm, decreases in average sperm path and straight line velocities, and
      minimal retention of mature sperm in the seminiferous tubules were observed at
      all dose-levels tested. These findings were unexpected in view of a lack of
      histopathological changes in the reproductive organs of either gender in 4-week
      repeat dose studies in rats and monkeys. A follow-up fertility study was
      conducted using an innovative flexible study design and a single high-dose level.
      In the first instance, treated male rats were mated with untreated females,
      followed by necropsy of a subset of males. The intention was then to re-mate the
      males after an 8-week wash-out period with either treated or untreated females
      depending on the outcome of the first mating. On this occasion, litter sizes were
      not affected, but the testicular effects were reproduced. A second mating with
      treated females reproduced the reduced litter sizes due to increased pre- and
      post-implantation loss, demonstrating that the effect on fecundity was female
      mediated. The testicular changes in males were shown to be reversible after a 12
      week recovery period.

PMID- 29635060
TI  - In vitro percutaneous penetration of silver nanoparticles in pig and human skin.
AB  - In this study, the effects of surface charge, dose, and cosmetic vehicle on the
      penetration of silver nanoparticles (AgNPs) into pig and human skin were
      compared. AgNPs (20 nm) with varying surface-charges (polyethylene glycol (PEG;
      neutral), citrate (CIT; negative), and branched polyethylenimine (bPEI; positive)
      were dosed onto skin in in vitro diffusion cells using an aqueous solution and an
      oil-in-water emulsion formulation. Samples were analyzed by inductively coupled
      plasma mass spectroscopy (ICP-MS) and transmission electron microscope (TEM) to
      assess AgNP skin penetration. The results showed that neutral and positive AgNPs
      penetrate human skin when applied in a high dose aqueous solution and less with
      the emulsion vehicle. A mass balance percutaneous penetration study in human skin
      found the majority of AgNPs were washed from the skin or remained mostly in the
      stratum corneum (3.4% of the applied dose for AgbPEI and 1.7% for AgPEG). Very
      little silver was found in the epidermis (1.2% AgbPEI and 0.3% AgPEG) and dermis
      (0.1% AgbPEI and none detected for AgPEG). These results indicate low dermal
      penetration of AgNPs that is not greatly affected by surface coating charge. The
      results will facilitate dermal exposure assessments by better understanding how
      nanoparticle properties affect skin absorption of nanoparticles found in personal
      care products.

PMID- 29635062
TI  - Computational design and experimental characterization of a novel beta-common
      receptor inhibitory peptide.
AB  - In short-term animal models of ischemia, erythropoietin (EPO) signaling through
      the heterodimeric EPO receptor (EPOR)/beta-common receptor (betaCR) is believed
      to elicit tissue protective effects. However, large, randomized, controlled
      trials demonstrate that targeting a higher hemoglobin level by administering
      higher doses of EPO, which are more likely to activate the heterodimeric
      EPOR/betaCR, is associated with an increase in adverse cardiovascular events.
      Thus, inhibition of long-term activation of the betaCR may have therapeutic
      implications. This study aimed to design and evaluate the efficacy of novel
      computationally designed betaCR inhibitory peptides (betaIP). These novel betaIPs
      were designed based on a truncated portion of Helix-A from EPO, specifically
      residues 11-26 (VLERYLLEAKEAEKIT). Seven novel peptides (P1 to P7) were designed.
      Peptide 7 (P7), VLERYLHEAKHAEKIT, demonstrated the most robust inhibitory
      activity. We also report here the ability of P7 to inhibit betaCR-induced nitric
      oxide (NO) production and angiogenesis in human umbilical vein endothelial cells
      (HUVECs). Specifically, we found that P7 betaIP completely abolished EPO-induced
      NO production. The inhibitory effect could be overcome with super physiological
      doses of EPO, suggesting a competitive inhibition. betaCR-induced angiogenesis in
      HUVEC's was also abolished with treatment of P7 betaIP, but P7 betaIP did not
      inhibit vascular endothelial growth factor (VEGF)-induced angiogenesis. In
      addition, we demonstrate that the novel P7 betaIP does not inhibit EPO-induced
      erythropoiesis with use of peripheral blood mononuclear cells (PBMCs). These
      results, for the first time, describe a novel, potent betaCR peptide inhibitor
      that inhibit the actions of the betaCR without affecting erythropoiesis.

PMID- 29635061
TI  - An open-label, randomized, four-treatment crossover study evaluating the effects
      of salt form, acetaminophen, and food on the pharmacokinetics of phenylephrine.
AB  - Phenylephrine hydrochloride (HCl) is a decongestant available in over-the-counter
      (OTC) medicines. Previously marketed prescription products contained
      phenylephrine tannate, an extended-release salt, which allowed dosing every 8-12
      h. Given the regulatory history that cold medicines marketed before 1962 had
      limited supporting clinical data, and with widespread replacement of
      pseudoephedrine by phenylephrine in OTC products over the last ten years, the
      need for contemporary studies grew. This exploratory crossover study evaluated
      effects of salt form, acetaminophen, and food on phenylephrine pharmacokinetics
      and metabolites in healthy adults. Test treatments were 25 mg phenylephrine
      tannate (equivalent to 10 mg phenylephrine HCl) combined with 200 mg guaifenesin,
      fasted; 10 mg phenylephrine HCl combined with 650 mg acetaminophen, fasted; and
      10 mg phenylephrine HCl, fed. The reference treatment was 10 mg phenylephrine
      HCl, fasted. Plasma phenylephrine pharmacokinetics and urine metabolites were
      determined. Although the tannate salt slowed phenylephrine absorption compared
      with the HCl salt, terminal concentrations were similar, suggesting that products
      containing the tannate salt should not be dosed less frequently than those
      containing the HCl salt. The premise that acetaminophen increases phenylephrine
      bioavailability by competition for presystemic sulfation was corroborated by
      increased phenylephrine sulfate in urine. Food delayed phenylephrine absorption,
      but not the total amount absorbed.

PMID- 29635063
TI  - The SAFE pathway is involved in the postconditioning mechanism of oxytocin in
      isolated rat heart.
AB  - Oxytocin (OT) has a postconditioning effect against the ischemia-reperfusion
      (I/R) injury. However, its precise cardioprotection mechanism at the early
      reperfusion phase remains under debate. Our previous study revealed that OT
      postconditioning (OTpost) is cardioprotective by activating the Reperfusion
      Injury Salvage Kinase (RISK) pathway. Therefore, the present study is aimed to
      determine the biological effects of OTpost via the OT receptor and the activation
      of the JAK/STAT3 signaling pathway, mitochondrial adenosine triphosphate
      dependent potassium channel (mitoKATP), nitric oxide (NO) release, and its anti
      apoptotic effects against I/R injury in an isolated rat heart model. Sixty-three
      rats were randomly allocated to one of nine groups. OT was perfused 40 min prior
      to the regional ischemia or 15 min at the early reperfusion phase. AG490 (a
      JAK/STAT3 inhibitor), 5HD (a mitoKATP blocker), atosiban (an OT receptor
      antagonist), L-NAME (a nonspecific nitric oxide synthase inhibitor) were applied
      either alone or in combination with OT during the pre-ischemia phase and/or in
      the early reperfusion phase. Myocardial infarct size, hemodynamic factor,
      ventricular arrhythmia, coronary flow, cardiac biochemical marker, and the
      apoptosis index were determined at the end of reperfusion. Oxytocin
      postconditioning reduced infarct size, lactate dehydrogenase activity, arrhythmia
      score, ventricular fibrillation, and apoptosis. Moreover, AG490, 5HD, atosiban,
      and L-NAME abrogated the cardioprotective effects of OT. Our results demonstrated
      that the cardioprotective effects of OT are mediated by NO release, and the
      activation of mitoKATP and the SAFE pathway through the JAK/STAT3 signaling
      cascade that finally lead to decrease in the apoptosis index during the early
      reperfusion phase.

PMID- 29635064
TI  - Regulation of oyster (Crassostrea virginica) hemocyte motility by the
      intracellular parasite Perkinsus marinus: A possible mechanism for host
      infection.
AB  - Hemocytes associated with the mucus lining of pallial (mantle, gill) surfaces of
      the oyster Crassostrea virginica have been recently suggested to facilitate
      infection by the Alveolate parasite Perkinsus marinus by mediating the uptake and
      dispersion of parasite cells. These "pallial hemocytes", which are directly
      exposed to microbes present in surrounding seawater, are able to migrate bi
      directionally between mucosal surfaces and the circulatory system, potentially
      playing a sentinel role. Interestingly, P. marinus was shown to increase trans
      epithelial migration of hemocytes suggesting it may regulate cell motility to
      favor infection establishment. The purpose of this study was to investigate the
      effect of P. marinus on hemocyte motility and identify specific molecular
      mechanisms potentially used by the parasite to regulate hemocyte migration. In a
      first series of experiments, various components of P. marinus (live P. marinus
      cells, extracellular products, fragments of P. marinus cell membrane, membrane
      modified live P. marinus cells, heat-killed P. marinus) along with components of
      the opportunistic bacterial pathogen Vibrio alginolyticus (bacterial cells and
      extracellular products) were investigated for their effects on hemocyte motility.
      In a second series of experiments, inhibitors of specific molecular pathways
      involved in motility regulation (Y-27632: inhibitor of Rho-associated protein
      kinase, RGDS: integrin inhibitor, CK-666: Arp2/3 inhibitor) were used in
      conjunction with qPCR gene expression experiments to identify pathways regulated
      by P. marinus exposure. Results showed a specific increase in hemocyte motility
      following exposure to live P. marinus cells. The increase in motility induced by
      P. marinus was suppressed by RGDS and CK-666 implicating the involvement of
      integrins and Arp2/3 in cell activation. Gene expression data suggest that Arp2/3
      is possibly regulated directly by an effector produced by P. marinus. The
      implications of increased hemocyte motility prompted by P. marinus during the
      early stage of the infection process are discussed.

PMID- 29635065
TI  - Cloning, characterization and functional analysis of dctn5 in immune response of
      Chinese tongue sole (Cynoglossus semilaevis).
AB  - In mammals, microtubule-dependent trafficking could participate the immune
      response, where the motor proteins are suggested to play an important role in
      this process, while the related study in fish was rare. In this study, dctn5, a
      subunit of dyactin complex for docking motor protein, was obtained by previous
      immune QTL screening. The full-length cDNAs of two dctn5 transcript variants were
      cloned and identified (named dctn5_tv1 and dctn5_tv2, respectively). Tissue
      distribution showed that dctn5_tv1 was widely distributed and high transcription
      was observed in immune tissue (skin), while dctn5_tv2 was predominantly detected
      in gonad and very low in other tissues. Time-course expression analysis revealed
      that dctn5_tv1 could be up-regulated in gill, intestine, skin, spleen, and kidney
      after Vibrio harveyi challenge. Moreover, recombinant Dctn5_tv1 exhibited high
      antimicrobial activity against Escherichia coli and Streptococcus agalactiae due
      to binding to bacteria cells. Taken together, these data suggest Dctn5_tv1 is
      involved in immune response of bacterial invasion in Chinese tongue sole.

PMID- 29635066
TI  - Dietary administration of the probiotic Shewanella putrefaciens Pdp11 promotes
      transcriptional changes of genes involved in growth and immunity in Solea
      senegalensis larvae.
AB  - Senegalese sole (Solea senegalensis) has been proposed as a high-potential
      species for aquaculture diversification in Southern Europe. It has been
      demonstrated that a proper feeding regimen during the first life stages
      influences larval growth and survival, as well as fry and juvenile quality. The
      bacterial strain Shewanella putrefaciens Pdp11 (SpPdp11) has shown very good
      probiotic properties in Senegalese sole, but information is scarce about its
      effect in the earliest stages of sole development. Thus, the aim of this study
      was to investigate the effect of SpPdp11, bioencapsulated in live diet,
      administered during metamorphosis (10-21 dph) or from the first exogenous feeding
      of Senegalese sole (2-21 dph). To evaluate the persistence of the probiotic
      effect, we sampled sole specimens from metamorphosis until the end of weaning
      (from 23 to 73 dph). This study demonstrated that probiotic administration from
      the first exogenous feeding produced beneficial effects on Senegalese sole larval
      development, given that specimens fed this diet exhibited higher and less
      dispersed weight, as well as increases in both total protein concentration and
      alkaline phosphatase activity, and in non-specific immune response. Moreover,
      real-time PCR documented changes in the expression of a set of genes involved in
      central metabolic functions including genes related to growth, genes coding for
      proteases (including several digestive enzymes), and genes implicated in the
      response to stress and in immunity. Overall, these results support the
      application of SpPdp11 in the first life stages of S. senegalensis as an
      effective tool with the clear potential to benefit sole aquaculture.

PMID- 29635067
TI  - Lysine 39 of IKKepsilon of black carp is crucial for its regulation on IRF7
      mediated antiviral signaling.
AB  - Interferon regulatory factor 7 (IRF7) plays a crucial role in the interferon
      (IFN) signaling in mammals, in which it is activated by the TBK1/IKKepsilon
      complex during host antiviral innate immune response. There are few reports about
      the relation between IRF7 and IKKepsilon in teleost fishes. In this study, the
      IRF7 homologue (bcIRF7) of black carp (Mylopharyngodon Piceus) has been cloned
      and characterized. The transcription of bcIRF7 gene increased in host cells in
      response to the stimulation of LPS, poly (I:C) and viral infection. bcIRF7
      migrated around 56 KDa in immunoblot assay and was identified as a predominantly
      cytosolic protein by immunofluorescent staining. bcIRF7 showed IFN-inducing
      ability in reporter assay and EPC cells expressing bcIRF7 showed enhanced
      antiviral ability against both grass carp reovirus (GCRV) and spring viremia of
      carp virus (SVCV). IKKepsilon of black carp (bcIKKepsilon) was found to be
      recruited into host innate immune response initiated by SVCV and GCRV in the
      previous work; in this paper, the kinase dead mutant of bcIKKepsilon,
      bcIKKepsilon-K39A was constructed and showed no IFN-inducing activity. The data
      of reporter assay and plaque assay demonstrated that bcIKKepsilon but not
      bcIKKepsilon-K39A obviously enhanced bcIRF7-mediated IFN production and antiviral
      activity. Our data support the conclusion that bcIKKepsilon upregulates bcIRF7
      mediated antiviral signaling, which most likely depends on its kinase activity.

PMID- 29635068
TI  - Anterior segment optical coherence tomography.
AB  - Optical coherence tomography (OCT) provides non-contact, rapid in vivo imaging of
      ocular structures, and has become a key part of evaluating the anterior segment
      of the eye. Over the years, improvements to technology have increased the speed
      of capture and resolution of images, leading to the increasing impact of anterior
      segment OCT imaging on clinical practice. In this review, we summarize the
      historical development of anterior segment OCT, and provide an update on the
      research and clinical applications of imaging the ocular surface, cornea,
      anterior chamber structures, aqueous outflow system, and most recently anterior
      segment vessels. We also describe advancements in anterior segment OCT technology
      that have improved understanding with greater detail, such as tear film in dry
      eye disease evaluation, intra-operative real-time imaging for anterior segment
      surgery, and aqueous outflow with angle assessment for glaucoma. Improvements to
      image processing and software have also improved the ease and utility of
      interpreting anterior segment OCT images in everyday clinical practice. Future
      developments include refinement of assessing vascular networks for the anterior
      segment, in vivo ultra-high resolution anterior segment optical coherence
      tomography with histology-like detail, en-face image with 3-dimensional
      reconstruction as well as functional extensions of the technique.

PMID- 29635069
TI  - Circular RNA ciRS-7 accelerates ESCC progression through acting as a miR-876-5p
      sponge to enhance MAGE-A family expression.
AB  - As the most well-known circular RNA, ciRS-7 (also termed CDR1as) has been
      reported to act as a miR-7 sponge, resulting in reduced miR-7 activity and
      increased miR-7-targeted transcripts. Here, we showed that ciRS-7 is up-regulated
      in esophageal squamous cell carcinoma (ESCC), and is associated with the poor
      clinicopathological parameters of ESCC patients. Moreover, over-expression of
      ciRS-7 increased the proliferation, migration and invasion of ESCC cells.
      Mechanistic studies revealed that ciRS-7 contains nineteen miR-876-5p binding
      sites and acts as a miR-876-5p sponge. Over-expression of ciRS-7 resulted in the
      reduced tumor-repressive function of miR-876-5p on its downstream target MAGE-A
      family. In animal experiments, enforced ciRS-7 increased ESCC tumor growth and
      metastasis through targeting miR-876-5p/MAGE-A family axis. Collectively, our
      study provided novel evidence that ciRS-7 accelerates ESCC progression by acting
      as a miR-876-5p sponge to enhance MAGE-A family expression.

PMID- 29635070
TI  - A density gradient of VAPG peptides on a cell-resisting surface achieves
      selective adhesion and directional migration of smooth muscle cells over
      fibroblasts.
AB  - : Selective adhesion and migration of smooth muscle cells (SMCs) over fibroblasts
      (FIBs) is required to prevent adventitia fibrosis in vascular regeneration. In
      this study, a uniform cell-resisting layer of poly(ethylene glycol) (PEG) with a
      density gradient of azide groups was generated on a substrate by immobilizing two
      kinds of PEG molecules in a gradient manner. A density gradient of alkynyl
      functionalized Val-Ala-Pro-Gly (VAPG) peptides was then prepared on the PEG layer
      via click chemistry. The VAPG density gradient was characterized by fluorescence
      imaging, revealing the gradual enhancement of the fluorescent intensity along the
      substrate direction. The adhesion and mobility of SMCs were selectively enhanced
      on the VAPG density gradient, leading to directional migration toward the higher
      peptide density (up to 84%). In contrast, the adhesion and mobility of FIBs were
      significantly weakened. The net displacement of SMCs also significantly increased
      compared with that on tissue culture polystyrene (TCPS) and that of FIBs on the
      gradient. The mitogen-activated protein kinase (MAPK) signaling pathways related
      to cell migration were studied, showing higher expressions of functional proteins
      from SMCs on the VAPG-modified surface in a density-dependent manner. For the
      first time the selective adhesion and directional migration of SMCs over FIBs was
      achieved by an elaborative design of a gradient surface, leading to a new insight
      in design of novel vascular regenerative materials. STATEMENT OF SIGNIFICANCE:
      Selective cell adhesion and migration guided by regenerative biomaterials are
      extremely important for the regeneration of targeted tissues, which can avoid the
      drawbacks of incorrect and uncontrolled responses of tissue cells to implants.
      For example, selectivity of smooth muscle cells (SMCs) over fibroblasts (FIBs) is
      required to prevent adventitia fibrosis in vascular regeneration. Herein we
      prepare a uniform cell-repelling layer, on which SMCs-selective Val-Ala-Pro-Gly
      (VAPG) peptides are immobilized in a continuous manner. Selective adhesion and
      enhanced and directional migration of SMCs over FIBs are achieved by the
      interplay of cell-repelling layer and gradient SMCs-selective VAPG peptides,
      paving a new way for the design of novel vascular grafts with enhanced biological
      performance.

PMID- 29635071
TI  - A case of typhoidal tularemia in a male Japanese farmer.
AB  - In Japan, most tularemia cases occur after contact with hares (hunting, cooking)
      and involve the glandular or ulceroglandular form. Here, we present a case of
      typhoidal tularemia in a 72-year-old Japanese male farmer who presented with
      fever, fatigue, and right lower abdominal pain. Computed tomography revealed
      intestinal wall thickening at the ascending colon, pleural effusion, and ascites.
      Following an initial diagnosis of bacterial enteric infection, his symptoms
      deteriorated after a week-long cephalosporin treatment course. The patient lived
      in an area endemic for scrub typhus; the antibiotic was changed to a tetracycline
      on suspicion of scrub typhus infection. His symptoms rapidly improved after
      initiation of minocycline treatment. Later, blood tests revealed marked increases
      in serological tests against Francisella tularensis exclusively, and the patient
      was diagnosed with typhoidal tularemia. Typhoidal tularemia may be characterized
      by any combination of general symptoms, but does not exhibit the local
      manifestations associated with other forms of tularemia. The patient, in this
      case, had no direct contact with hares or other wild animals and did not present
      with local manifestations of tularemia. Physicians should consider this disease,
      especially when tick-borne disease is suspected in the absence of local wounds,
      eschar, ulcers, or lymphadenopathy.

PMID- 29635072
TI  - Modelling nasal high flow therapy effects on upper airway resistance and
      resistive work of breathing.
AB  - AIM: The goal of this paper is to quantify upper airway resistance with and
      without nasal high flow (NHF) therapy. For adults, NHF therapy feeds 30-60 L/min
      of warm humidified air into the nose through short cannulas which do not seal the
      nostril. NHF therapy has been reported to increase airway pressure, increase
      tidal volume (Vt) and decrease respiratory rate (RR), but it is unclear how these
      findings affect the work done to overcome airway resistance to air flow during
      expiration. Also, there is little information on how the choice of nasal cannula
      size may affect work of breathing. In this paper, estimates of airway resistance
      without and with different NHF flow (applied via different cannula sizes) were
      made. The breathing efforts required to overcome airway resistance under these
      conditions were quantified. METHOD: NHF was applied via three different cannula
      sizes to a 3-D printed human upper airway. Pressure drop and flow rate were
      measured and used to estimate inspiratory and expiratory upper airway
      resistances. The resistance information was used to compute the muscular work
      required to overcome the resistance of the upper airway to flow. RESULTS: NHF
      raises expiratory resistance relative to spontaneous breathing if the breathing
      pattern does not change but reduces work of breathing if peak expiratory flow
      falls. Of the cannula sizes used, the large cannula produced the greatest
      resistance and the small cannula produced the least. The work required to cause
      tracheal flow through the upper airway was reduced if the RR and minute volume
      are reduced by NHF. NHF has been observed to do so in COPD patients (Braunlich et
      al., 2013). A reduction in I:E ratio due to therapy was found to reduce work of
      breathing if the peak inspiratory flow is less than the flow below which no
      inspiratory effort is required to overcome upper airway resistance. CONCLUSION:
      NHF raises expiratory resistance but it can reduce the work required to overcome
      upper airway resistance via a fall in inspiratory work of breathing, RR and
      minute volume.

PMID- 29635073
TI  - Modeling and optimization of nebulizers' performance in non-invasive ventilation
      using different fill volumes: Comparative study between vibrating mesh and jet
      nebulizers.
AB  - BACKGROUNDS: Substituting nebulisers by another, especially in non-invasive
      ventilation (NIV), involves many process-variables, e.g. nebulizer-type and fill
      volume of respirable-dose, which might affect patient optimum-therapy. The aim of
      the present work was to use neural-networks and genetic-algorithms to develop
      performance-models for two different nebulizers. METHODS: In-vitro, ex-vivo and
      in-vivo models were developed using input-variables including nebulizer-type [jet
      nebulizer (JN) and vibrating mesh nebulizer (VMN)] fill-volumes of respirable
      dose placed in the nebulization chamber with an output-variable e.g. average
      amount reaching NIV patient. Produced models were tested and validated to ensure
      effective predictivity and validity in further optimization of nebulization
      process. RESULTS: Data-mining produced models showed excellent training, testing
      and validation correlation-coefficients. VMN showed high nebulization efficacy
      than JN. JN was affected more by increasing the fill-volume. The optimization
      process and contour-lines obtained for in-vivo model showed increase in pulmonary
      bioavailability and systemic-absorption with VMN and 2 mL fill-volumes.
      CONCLUSIONS: Modeling of aerosol-delivery by JN and VMN using different fill
      volumes in NIV circuit was successful in demonstrating the effect of different
      variable on dose-delivery to NIV patient. Artificial neural networks model showed
      that VMN increased pulmonary-bioavailability and systemic-absorption compared to
      JN. VMN was less affected by fill-volume change compared to JN which should be
      diluted to increase delivery.

PMID- 29635074
TI  - STEM and APT characterization of scale formation on a La,Hf,Ti-doped NiCrAl model
      alloy.
AB  - A thermally grown scale formed on a cast NiCrAl model alloy doped with lanthanum,
      hafnium, and titanium was examined after isothermal exposure at 1100  degrees C
      for 100 h in dry flowing O2 to understand the dopant segregation along scale
      grain boundaries. The complex scale formed on the alloy surface was composed of
      two types of substrates: phase-dependent, thin (<250 nm) outer layers and a
      columnar-grained ~3.5 MUm inner alumina layer. Two types of oxides formed between
      the inner and outer scale layers: small (3-15 nm) La2O3 and larger (<=50 nm) HfO2
      oxide precipitates. Nonuniform distributions of the hafnium, lanthanum, and
      titanium dopants were observed along the inner scale grain boundaries, with
      hafnium dominating in most of the grain boundaries of alpha-Al2O3. The
      concentration of reactive elements (RE) seemed to strongly depend on the grain
      boundary structure. The level of titanium grain boundary segregation in the inner
      scale decreased toward the model alloy (substrate), confirming the fast outward
      diffusion of titanium. Hafnium was also observed at the metal-scale interface and
      in the gamma' (Ni3Al) phase of the alloy. High-resolution scanning transmission
      electron microscopy (STEM) confirmed the substitution of REs for aluminum atoms
      at the scale grain boundaries, consistent with both the semiconducting band
      structure and the site-blocking models. Both STEM and atom probe tomography
      allowed quantification of REs along the scale grain boundaries across the scale
      thickness. Analysis of the scale morphology after isothermal exposure in flowing
      oxygen revealed a myriad of new precipitate phases, RE segregation dependence on
      grain boundary type, and atomic arrangement along scale grain boundaries, which
      is expected to influence the scale growth rate, stability, and mechanical
      properties.

PMID- 29635075
TI  - From HSV infection to erythema multiforme through autoimmune crossreactivity.
AB  - Scientific and clinical data indicate that human herpes simplex virus 1 (HSV1)
      and, at a lesser extent, human herpes simplex virus 2 (HSV2) are factor(s)
      implicated in the development of erythema multiforme (EM). With a focus on oral
      EM, the present structured review of proteomic and epitope databases searched for
      the molecular basis that might link HSV1 and HSV2 infections to EM. It was found
      that a high number of peptides are shared between the two HSVs and human proteins
      related to the oral mucosa. Moreover, a great number of the shared peptides are
      also present in epitopes that have been experimentally validated as
      immunopositive in the human host. The results suggest the involvement of HSV
      infections in the induction of oral EM via a mechanism of autoimmune cross
      reactivity and, in particular, highlight a potential major role for 180kDa
      bullous pemphigoid antigen and HSV1 infection in the genesis of crossreactions
      potentially conducive to EM.

PMID- 29635076
TI  - The role of ophthalmic imaging in central nervous system degeneration in systemic
      lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disorder
      that can involve any organ system. Central nervous system involvement can be a
      severe life threatening complication, ultimately resulting in severe
      neurodegenerative changes. Magnetic resonance imaging suggests that
      neurodegeneration, which may have deleterious effects on brain function, may
      occur early in SLE and experimental models suggest that neuroprotection may be
      feasible and beneficial. The retina is an extension of the brain. Recent
      ophthalmic imaging technologies are capable of identifying early changes in
      retinal and choroidal morphology and circulation that may reflect CNS
      degeneration. However, their utility in monitoring CNS involvement in SLE has
      been poorly studied as these have only been performed in small cohorts, in a
      cross-sectional design, non-quantitatively and without correlation to disease
      activity. The authors aim to review the current understanding of
      neurodegeneration associated with SLE, with particular focus on the visual
      pathway. We describe the neuropathology of the visual system in SLE and the
      evidence for retinal and choroidal neurodegenerative and microvascular changes
      using optical coherence tomography technology. We aim to describe the potential
      role of optical imaging modalities in NPSLE diagnosis and their likely impact on
      the study of neuronal function.

PMID- 29635077
TI  - Systemic lupus erythematosus and systemic sclerosis: All roads lead to platelets.
AB  - Systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) are two
      phenotypically distincts inflammatory systemic diseases. However, SLE and SSc
      share pathogenic features such as interferon signature, loss of tolerance against
      self-nuclear antigens and increased tissue damage such as fibrosis. Recently,
      platelets have emerged as a major actor in immunity including auto-immune
      diseases. Both SLE and SSc are characterized by strong platelet system
      activation, which is likely to be both the witness and culprit in their
      pathogenesis. Platelet activation pathways are multiple and sometimes redundant.
      They include immune complexes, Toll-like receptors activation, antiphospholipid
      antibodies and ischemia-reperfusion associated with Raynaud phenomenon. Once
      activated, platelet promote immune dysregulation by priming interferon production
      by immune cells, providing CD40L supporting B lymphocyte functions and providing
      a source of autoantigens. Platelets are actively implicated in SLE and SSc end
      organ damage such as cardiovascular and renal disease and in the promotion of
      tissue fibrosis. Finally, after understanding the main pathogenic implications of
      platelet activation in both diseases, we discuss potential therapeutics targeting
      platelets.

PMID- 29635078
TI  - Genetic variation and systemic lupus erythematosus: A field synopsis and
      systematic meta-analysis.
AB  - Systemic lupus erythematosus (SLE) is a multi-systemic severe autoimmune disease
      which results from the irreversible loss of self-tolerance and impaired molecular
      responses, especially an altered interferon signature. We synthesized all meta
      analyses reporting a genetic association of SLE, and further investigated their
      validity to discover false positive results under Bayesian methods. We executed a
      PubMed search to extract the respective results regarding gene polymorphisms of
      SLE, published until June 30th 2017 and selected a single result per genetic
      variant among duplicates. Among 133 significant genotype comparisons, 45 (34%)
      were found noteworthy under both false positive report probability (FPRP) and
      Bayesian false discovery probability (BFDP). From the meta-analysis of genome
      wide association studies (GWAS), we could confirm that all significant
      comparisons were noteworthy under both Bayesian approaches. Both approaches may
      be advantageous for determining whether the reported associations are genuine,
      especially for interpreting results from observational studies instead of GWAS
      whose significance was determined in a more strict manner. When determining
      results from GWAS with a p-value ranging between 0.05 and 5 * 10-8, other
      statistical approaches, rather than single standard significance may be
      beneficial. Taking into account these considerations, a proportion of meta
      analyses claimed statistical significance, but these results need to be
      interpreted with caution.

PMID- 29635079
TI  - Antinuclear antibodies: Is the indirect immunofluorescence still the gold
      standard or should be replaced by solid phase assays?

PMID- 29635080
TI  - Efficacy and safety of rituximab in systemic sclerosis: French retrospective
      study and literature review.
AB  - OBJECTIVE: To describe safety and efficacy of rituximab in patients with systemic
      sclerosis. METHODS: We included 13 patients with systemic sclerosis treated with
      rituximab and pooled with 40 additional patients from the literature. SSc
      rituximab untreated patients were matched to rituximab treated ones. RESULTS:
      Thirteen patients who received rituximab and 26 rituximab-untreated patients were
      included. In comparison to 26 patients who did not received rituximab, FVC
      changes were not significantly different, whereas DLCO improved in 13 patients
      who received rituximab (0 [-4; 4] vs loss of -7 [-19; 0]; p=0.05). Considering 7
      rituximab treated and 14 untreated diffuse SSc, FVC was improved during the 24
      [12; 46] months of follow up in dSSc who received rituximab (gain of 12 [7.5:14]
      % vs loss of 1.5 [-16.8; 2.5], (p=0.003)). Pooled analysis of 53 patients (40
      literature patients and 13 from personal series) showed significant improvement
      of median mRSS from 18 [8; 32] at baseline to 9 [4; 18] at M6 (p=0.007), 13 [8;
      18] at M12 (p=0.008) and 10 [4; 16] at the last follow-up (p=0.0002). FVC
      increased from 71% [66; 80] at baseline to 84% [75; 90] at M12 (p=0.001). DLCO
      increased from 58% [39; 65] at M0 to 63% [53; 78] at M12 (p=0.04). CONCLUSION:
      Our personal data and pooled literature analysis suggest the efficacy of
      rituximab in the subset of diffuse SSc in particular in skin and interstitial
      disease involvements. The safety of rituximab seems to be reasonable and similar
      to previous data in other autoimmune diseases.

PMID- 29635081
TI  - Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Evidence for an autoimmune
      disease.
AB  - Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a frequent and
      severe chronic disease drastically impairing life quality. The underlying
      pathomechanism is incompletely understood yet but there is convincing evidence
      that in at least a subset of patients ME/CFS has an autoimmune etiology. In this
      review, we will discuss current autoimmune aspects for ME/CFS. Immune
      dysregulation in ME/CFS has been frequently described including changes in
      cytokine profiles and immunoglobulin levels, T- and B-cell phenotype and a
      decrease of natural killer cell cytotoxicity. Moreover, autoantibodies against
      various antigens including neurotransmitter receptors have been recently
      identified in ME/CFS individuals by several groups. Consistently, clinical trials
      from Norway have shown that B-cell depletion with rituximab results in clinical
      benefits in about half of ME/CFS patients. Furthermore, recent studies have
      provided evidence for severe metabolic disturbances presumably mediated by serum
      autoantibodies in ME/CFS. Therefore, further efforts are required to delineate
      the role of autoantibodies in the onset and pathomechanisms of ME/CFS in order to
      better understand and properly treat this disease.

PMID- 29635083
TI  - Tuning of elasticity and surface properties of hydrogel cell culture substrates
      by simple chemical approach.
AB  - When designing materials for tissue engineering applications various parameters
      characterizing both materials and tissue have to be taken into account. The
      characteristics such as chemistry, elasticity, wettability, roughness and
      morphology of the substrate's surface have significant impact on cell behavior.
      The paper presents biopolymer (collagen/chitosan) based hydrogel materials with
      tunable elasticity and surface properties useful for fabrication of substrates
      for cell culture. Using simple chemical approach involving the change in
      concentration of crosslinking agent (genipin) and composition of the reaction
      mixture the hydrogels characterized with various features were obtained. Detailed
      analysis of morphology, topography, roughness and elasticity of surface performed
      using Scanning Electron Microscopy (SEM), Atomic Force Microscopy (AFM) and
      rheological measurements has shown that the topographical aspects and roughness
      parameter can be modulated in nanoscale regime (13-47 nm). Substrate's elasticity
      could be modified in a wide range (0.2-270 kPa). Biological in vitro studies on
      fibroblasts behavior revealed that the materials prepared provide satisfactory
      conditions for cell culture, ensuring their high viability, good adhesion and
      normal morphology. The genipin crosslinked collagen-chitosan hydrogels
      characterized by denser fiber structure, higher elasticity and lower surface
      roughness are the most attractive supports for fibroblasts cultivation. The
      results obtained indicate that the properties of the materials developed can be
      easily tailored to the needs of the given type of cells.

PMID- 29635082
TI  - Intraperitoneal nanotherapy for metastatic ovarian cancer based on siRNA-mediated
      suppression of DJ-1 protein combined with a low dose of cisplatin.
AB  - Herein, we report an efficient combinatorial therapy for metastatic ovarian
      cancer based on siRNA-mediated suppression of DJ-1 protein combined with a low
      dose of cisplatin. DJ-1 protein modulates, either directly or indirectly,
      different oncogenic pathways that support and promote survival, growth, and
      invasion of ovarian cancer cells. To evaluate the potential of this novel
      therapy, we have engineered a cancer-targeted nanoplatform and validated that DJ
      1 siRNA delivered by this nanoplatform after intraperitoneal injection
      efficiently downregulates the DJ-1 protein in metastatic ovarian cancer tumors
      and ascites. In vivo experiments revealed that DJ-1 siRNA monotherapy
      outperformed cisplatin alone by inhibiting tumor growth and increasing survival
      of mice with metastatic ovarian cancer. Finally, three cycles of siRNA-mediated
      DJ-1 therapy in combination with a low dose of cisplatin completely eradicated
      ovarian cancer tumors from the mice, and there was no cancer recurrence detected
      for the duration of the study, which lasted 35 weeks.

PMID- 29635084
TI  - Horseradish peroxidase-nanoclay hybrid particles of high functional and colloidal
      stability.
AB  - Highly stable dispersions of enzyme-clay nanohybrids of excellent horseradish
      peroxidase activity were developed. Layered double hydroxide nanoclay was
      synthesized and functionalized with heparin polyelectrolyte to immobilize the
      horseradish peroxidase enzyme. The formation of a saturated heparin layer on the
      platelets led to charge inversion of the positively charged bare nanoclay and to
      highly stable aqueous dispersions. Great affinity of the enzyme to the surface
      modified platelets resulted in strong horseradish peroxidase adsorption through
      electrostatic and hydrophobic interactions as well as hydrogen bonding network
      and prevented enzyme leakage from the obtained material. The enzyme kept its
      functional integrity upon immobilization and showed excellent activity in
      decomposition of hydrogen peroxide and oxidation of an aromatic compound in the
      test reactions. In addition, remarkable long term functional stability of the
      enzyme-nanoclay hybrid was observed making the developed colloidal system a
      promising antioxidant candidate in biomedical treatments and industrial
      processes.

PMID- 29635085
TI  - Synthesis of triblock copolymeric micelle based on poly (ethylene glycol) and
      poly (vinyl acetate) through reversible addition-fragmentation chain transfer
      polymerization.
AB  - HYPOTHESIS: Polymeric micelles are fabricated by the self-aggregation of
      amphiphilic polymers in aqueous medium. Amphiphilic block copolymers consist of
      hydrophobic and hydrophilic blocks. The hydrophilic blocks form corona, while
      hydrophobic blocks produce core of the micelle. EXPERIMENTS: In the present
      manuscript, a triblock copolymer derived from poly (ethylene glycol) and poly
      (vinyl acetate) (PVAc-b-PEG200-b-PVAc) has been prepared via reversible addition
      fragmentation chain transfer polymerization. Its structural properties as well as
      micellar stability have been studied and application as dye carrier has been
      discussed in details. FINDINGS: The GPC analysis shows the low polydispersity of
      the developed copolymer that signifies the controlled nature of polymerization.
      The copolymer demonstrates long-term micellar stability, which has been
      determined by dynamic light scattering (DLS) analysis. The block copolymer
      reveals excellent pH-triggered release behavior of loaded Nile red, which
      ascertained the dye carrier feature of PVAc-b-PEG200-b-PVAc.

PMID- 29635086
TI  - Interaction between U(VI) with sulfhydryl groups functionalized graphene oxides
      investigated by batch and spectroscopic techniques.
AB  - A novel 4-aminothiophenol functionalized graphene oxide composite (GO-SH) was
      prepared by an easy reaction route. Chemical structure and element analysis
      showed that the sulfhydryl groups (-SH) were successfully decorated on GOs. The
      sorption capacity toward U(VI) from aqueous solution was conducted by batch
      experiments. The results indicated the maximum sorption capacity of GO-SH
      composite toward U(VI) at pH = 5.5 and T = 298 K could reach 281.69 mg.g-1 on the
      base of the Langmuir model. The sorption kinetic curve for U(VI) fitted well with
      the pseudo-second-order model. X-ray photoelectron spectroscopy and infrared
      analysis demonstrated that the surface-grafted sulfhydryl groups contributed to
      the sorption of U(VI) by forming the surface complexation. The GO-SH also showed
      high stability and excellent reuse capability. Therefore, GO-SH can be regarded
      as a potential sorbent for the efficient removal of U(VI) from aqueous solutions.

PMID- 29635087
TI  - Carbon materials-functionalized tin dioxide nanoparticles toward robust, high
      performance nitrogen dioxide gas sensor.
AB  - Carbon (C) materials, which process excellent electrical conductivity and high
      carrier mobility, are promising sensing materials as active units for gas
      sensors. However, structural agglomeration caused by chemical processes results
      in a small resistance change and low sensing response. To address the above
      issues, structure-derived carbon-coated tin dioxide (SnO2) nanoparticles having
      distinct core-shell morphology with a 3D net-like structure and highly uniform
      size are prepared by careful synthesis and fine structural design. The optimum
      carbon-coated SnO2 nanoparticles (SnO2/C)-based gas sensor exhibits a low working
      temperature, excellent selectivity and fast response-recovery properties. In
      addition, the SnO2/C-based gas sensor can maintain a sensitivity to nitrogen
      dioxide (NO2) of 3 after being cycled 4 times at 140  degrees C for, suggesting
      its good long-term stability. The structural integrity, good synergistic
      properties, and high gas-sensing performance of SnO2/C render it a promising
      sensing material for advanced gas sensors.

PMID- 29635088
TI  - PdCo nanoparticles supported on carbon fibers derived from cotton: Maximum
      utilization of Pd atoms for efficient reduction of nitroarenes.
AB  - In the present work, a facile and environment-friendly route is illustrated for
      the efficient fabrication of highly dispersed PdCo nanoparticles (NPs) by
      modified cotton-derived carbon fibers (PdCo/CCF). Firstly, commercial cotton was
      impregnated with CoCl2, followed by pyrolysis under high calcination temperature
      to obtain the Co NPs modified CCF sample (Co/CCF). Secondly, Co/CCF was treated
      with Pd(AcO)2 aqueous solution, wherein, through a spontaneous replacement
      reaction process, Pd2+ is reduced to metallic Pd and mostly covered on the
      surface of the Co NPs. Thus, the PdCo/CCF catalyst was obtained avoiding the use
      of toxic reductants like NaBH4, NH2NH2 and HCHO. The PdCo/CCF catalyst exhibits
      excellent catalytic activity and recyclability for the reduction of 4-nitrophenol
      and other nitroarenes compared with Pd/CCF, PdCo NPs and many other noble metals
      based catalysts. The reasons could be attributed to the uniformly dispersed and
      accessible PdCo NPs on the surface of the CCF, and the Pd atoms deposited on the
      Co NPs surface that makes the Pd active sites available for optimum use. The
      PdCo/CCF catalyst also exhibits potential application for catalytic reduction of
      nitroarenes in a fixed bed reactor under mild reaction conditions. Furthermore,
      the PdCo/CCF catalyst can be magnetically recycled and reused for at least ten
      cycles without either losing catalytic activity or leaching of Pd active sites,
      thereby confirming its superior stability.

PMID- 29635089
TI  - Metal-organic framework derived Fe/Fe3C@N-doped-carbon porous hierarchical
      polyhedrons as bifunctional electrocatalysts for hydrogen evolution and oxygen
      reduction reactions.
AB  - The development of simple and cost-effective synthesis methods for
      electrocatalysts of hydrogen evolution reaction (HER) and oxygen reduction
      reaction (ORR) is critical to renewable energy technologies. Herein, we report an
      interesting bifunctional HER and ORR electrocatalyst of Fe/Fe3C@N-doped-carbon
      porous hierarchical polyhedrons (Fe/Fe3C@N-C) by a simple metal-organic framework
      precursor route. The Fe/Fe3C@N-C polyhedrons consisting of Fe and Fe3C
      nanocrystals enveloped by N-doped carbon shells and accompanying with some carbon
      nanotubes on the surface were prepared by thermal annealing of Zn3[Fe(CN)6]2.xH2O
      polyhedral particles in nitrogen atmosphere. This material exhibits a large
      specific surface area of 182.5 m2 g-1 and excellent ferromagnetic property.
      Electrochemical tests indicate that the Fe/Fe3C@N-C hybrid has apparent HER
      activity with a relatively low overpotential of 236 mV at the current density of
      10 mA cm-2 and a small Tafel slope of 59.6 mV decade-1. Meanwhile, this material
      exhibits excellent catalytic activity toward ORR with an onset potential (0.936 V
      vs. RHE) and half-wave potential (0.804 V vs. RHE) in 0.1 M KOH, which is
      comparable to commercial 20 wt% Pt/C (0.975 V and 0.820 V), and shows even better
      stability than the Pt/C. This work provides a new insight to developing multi
      functional materials for renewable energy application.

PMID- 29635090
TI  - An investigation on the seasonal variations of the biomarkers of oxidative stress
      response and their correlations to Polonium-210 in mussel (Mytilus
      galloprovincialis) and common sole (Solea solea) from Izmir Bay, Turkey.
AB  - It is well known that the marine organisms are used as biological indicators for
      environmental pollution studies. Among these studies, the research on oxidative
      stress has been increasing in recent years. In this study, mussels (Mytilus
      galloprovincialis) and fish (Solea solea) samples were collected seasonally from
      Inciralti, Izmir, Turkey. This station was in an area where fishing is carried
      out for human consumption. The relationship between 210Po and oxidative stress
      markers (lipid peroxidation (LPO), H2O2 and proline) was investigated in the
      mussel tissue (digestive gland, gills) and fish tissue (liver, gills) samples.
      The present study indicated that H2O2 accumulated with increasing 210Po
      concentration in mussel samples. Statistically significant correlation were found
      between H2O2 and 210Po and LPO and proline in mussel samples. This correlation
      between LPO and proline can be attributed to common environmental parameters
      (other than 210Po) affecting expression of both LPO and proline levels. There was
      not a significant correlation between 210Po and LPO levels. Similarly, a
      significant correlation was not found between 210Po and proline.

PMID- 29635091
TI  - Co-combustion of anthracite coal and wood pellets: Thermodynamic analysis,
      combustion efficiency, pollutant emissions and ash slagging.
AB  - This work presents studies on the co-combustion of anthracite coal and wood
      pellets in fluidized bed. Prior to the fluidized bed combustion,
      thermogravimetric analysis are performed to investigate the thermodynamic
      behavior of coal and wood pellets. The results show that the thermal
      decomposition of blends is divided into four stages. The co-firing of coal and
      wood pellets can promote the combustion reaction and reduce the emission of
      gaseous pollutants, such as SO2 and NO. It is important to choose the proportion
      of wood pellets during co-combustion due to the low combustion efficiency caused
      by large pellets with poor fluidization. Wood pellets can inhibit the
      volatilization of trace elements, especially for Cr, Ni and V. In addition, the
      slagging ratio of wood pellets ash is reduced by co-firing with coal. The
      research on combustion of coal and wood pellets is of great significance in
      engineering.

PMID- 29635092
TI  - Time trend in the impact of heat waves on daily mortality in Spain for a period
      of over thirty years (1983-2013).
AB  - Many of the studies that analyze the future impact of climate change on mortality
      assume that the temperature that constitutes a heat wave will not change over
      time. This is unlikely, however, given the process of adapting to heat changes,
      prevention plans, and improvements in social and health infrastructure. The
      objective of this study is to analyze whether, during the 1983-2013 period, there
      has been a temporal change in the maximum daily temperatures that constitute a
      heat wave (Tthreshold) in Spain, and to investigate whether there has been
      variation in the attributable risk (AR) associated with mortality due to high
      temperatures in this period. This study uses daily mortality data for natural
      causes except accidents CIEX: A00-R99 in municipalities of over 10,000
      inhabitants in 10 Spanish provinces and maximum temperature data from
      observatories located in province capitals. The time series is divided into three
      periods: 1983-1992, 1993-2003 and 2004-2013. For each period and each province,
      the value of Tthreshold was calculated using scatter-plot diagram of the daily
      mortality pre-whitened series. For each period and each province capitals, it has
      been calculated the number of heat waves and quantifying the impact on mortality
      through generalized linear model (GLM) methodology with the Poisson regression
      link. These models permits obtained the relative risks (RR) and attributable
      risks (AR). Via a meta-analysis, using the Global RR and AR were calculated the
      heat impact for the total of the 10 provinces. The results show that in the first
      two periods RR remained constant RR: 1.14 (CI95%: 1.09 1.19) and RR: 1.14 (CI95%:
      1.10 1.18), while the third period shows a sharp decrease with respect to the
      prior two periods RR: 1.01 (CI95%: 1.00 1.01); the difference is statistically
      significant. In Spain there has been a sharp decrease in mortality attributable
      to heat over the past 10 years. The observed variation in RR puts into question
      the results of numerous studies that analyze the future impact of heat on
      mortality in different temporal scenarios and show it to be constant over time.

PMID- 29635093
TI  - An approach estimating the short-term effect of NO2 on daily mortality in Spanish
      cities.
AB  - BACKGROUND: Road traffic is the most significant source of urban air pollution.
      PM2.5 is the air pollutant whose health effects have been most closely studied,
      and is the variable most commonly used as a proxy indicator of exposure to air
      pollution, whereas evidence on NO2 concentrations per se is still under study. In
      the case of Spain, there are no specific updated studies which calculate short
      term NO2-related mortality. OBJECTIVE: To quantify the relative risks (RRs) and
      attributable risks (ARs) of daily mortality associated with NO2 concentrations
      recorded in Spain across the study period, 2000-2009; and to calculate the number
      of NO2-related deaths. MATERIAL AND METHODS: We calculated daily mortality due to
      natural causes (ICD-10: A00 R99), circulatory causes (ICD-10: I00 I99) and
      respiratory causes (ICD-10: J00 J99) for each province across the period 2000
      2009, using data supplied by the National Statistics Institute. Mean daily NO2
      concentrations in MUg/m3 for each provincial capital were furnished by the
      Ministry of Agriculture & Environment, along with the equivalent figures for the
      control pollutants (PM10). To estimate RRs and ARs, we used generalised linear
      models with a Poisson link, controlling for maximum and minimum daily
      temperature, trend of the series, seasonalities, and the autoregressive nature of
      the series. A meta-analysis with random effects was used to estimate RRs and ARs
      nationwide. RESULTS: The overall RRs obtained for Spain, corresponding to
      increases of 10 MUg/m3 in NO2 concentrations were 1.012 (95% CI: 1.010 1.014) for
      natural-cause mortality, 1.028 (95% CI: 1.019 1.037) for respiratory-cause
      mortality, and 1.016 (95% CI: 1.012 1.021) for circulatory-cause mortality. This
      amounted to an annual overall 6085 deaths (95% CI: 3288 9427) due to natural
      causes, 1031 (95% CI: 466 1585) due to respiratory causes, and 1978 (95% CI: 828
      3197) due to circulatory causes. CONCLUSION: By virtue of the number of cities
      involved and the nature of the analysis performed, with quantification of the RRs
      and ARs of the short-term impact of NO2 on daily mortality in Spain, this study
      provides an updated estimate of the effect had by this type of pollutant on
      causes of mortality, and constitutes an important basis for reinforcing public
      health measures at a national level.

PMID- 29635094
TI  - Comment on 'Pharmacokinetics of bisphenol S in humans after a single oral
      administration'.

PMID- 29635095
TI  - Investigation of the photolysis and TiO2, SrTiO3, H2O2-mediated photocatalysis of
      an antipsychotic drug loxapine - Evaluation of kinetics, identification of
      photoproducts, and in silico estimation of properties.
AB  - The photolytic and photocatalytic transformation of loxapine with the use of
      H2O2, TiO2 and SrTiO3 under the simulated solar radiation was studied. A micro
      scale method for simultaneous irradiation of multiple samples in photostability
      chamber was applied. RP-UHPLC-DAD coupled with ESI-Q-TOF mass spectrometer was
      used for the quantitative and qualitative analysis of the processes. Influence of
      catalysts concentration on kinetic parameters of loxapine photodecomposition was
      evaluated, and TiO2 at medium concentration (100 mg L-1) turned out to be the
      most effective. Sixteen transformation products were detected and their
      structures were elucidated. On the basis of the elucidated structures,
      computational evaluation of toxicity, bioconcentration and bioaccumulation
      factors as well as biodegradability of transformation products were conducted.
      The multivariate chemometric method (principal component analysis) was used to
      compare the calculated properties as well as the applied methods. Most of the
      transformation products were generally less toxic and more biodegradable than the
      parent compound.

PMID- 29635096
TI  - Titanocene binding to oligonucleotides.
AB  - The binding of titanocene to DNA and RNA was examined by means of electrospray
      mass spectrometry. Titanocene served as a model for its therapeutically active
      derivatives. The binding preferences were probed by competition experiments with
      oligonucleotides of varying nucleobase compositions and sequences. Results from
      competition experiments revealed a generally increased preference for the binding
      to phosphate groups adjacent to thymidines, which is affected by the nucleobase
      sequence of T-rich oligonucleotides. More detailed information about the binding
      sites was obtained from tandem mass spectrometric experiments. The binding of the
      transition metal coordination center significantly altered the fragment ion
      patterns of the oligonucleotides. RNA was found to be less prone to adduct
      formation, due to intramolecular interactions. The findings from experiments on
      DNA and RNA were complemented by the examination of backbone- and ribose-modified
      oligonucleotides.

PMID- 29635097
TI  - EPR evidence for a fast-relaxing iron center in Na+-translocating NADH:quinone
      oxidoreductase.
AB  - A paramagnetic Cys4[Fe] center was detected by pulse EPR in Na+-translocating
      NADH:quinone-oxidoreductase (Na+-NQR) by influence of this center on transverse
      and longitudinal spin relaxation of Na+-NQR flavin radicals. The oxidation state
      of the Cys4[Fe] center was Fe3+ in the oxidized and Fe2+ in the reduced Na+-NQR,
      as deduced from the temperature dependence of spin relaxation rates of different
      flavin radicals. A high-spin state of iron in the Cys4[Fe] center was assigned to
      both forms of Na+-NQR.

PMID- 29635098
TI  - Evolution of phosphotriesterase activities of the metallo-beta-lactamase family:
      A theoretical study.
AB  - Metallo-beta-lactamase (MbetaL) is a eubacterial zinc metallo-hydrolase
      superfamily. Despite their well-known lactamase activities, MbetaL family members
      also have the ability to catalyze phosphotriester hydrolysis with different
      phosphotriesterase activities. In the present study, based on crystal structure
      comparisons of the related MbetaL members, a series of models was constructed and
      calculated using the density functional theory (DFT) method to explore the
      relationship between active-site changes and phosphotriesterase activities. These
      calculations show that the energetic barriers for phosphotriesterase activity are
      considerably reduced due to active-site differences, which describes an
      evolutionary trend for the development of phosphotriesterase activity in the
      MbetaL superfamily. The key event is the appearance of a specialized and
      negatively charged residue bridging both zinc ions, which plays the two important
      roles of maintaining charge balance and stabilizing the binuclear active-site
      structure. This pathway is also consistent with the evolutionary relationships
      determined by phylogenetic tree analysis using complete residue sequences. Our
      studies provide the first methodology to explore the development of a new enzyme
      activity within a superfamily, and to shed new light on understanding the
      catalytic mechanism from an evolutionary perspective.

PMID- 29635099
TI  - The relationship between mismatch response and the acoustic change complex in
      normal hearing infants.
AB  - OBJECTIVE: To examine the utility of the mismatch response (MMR) and acoustic
      change complex (ACC) for assessing speech discrimination in infants. METHODS:
      Continuous EEG was recorded during sleep from 48 (24 male, 20 female) normally
      hearing aged 1.77 to -4.57 months in response to two auditory discrimination
      tasks. ACC was recorded in response to a three-vowel sequence (/i/-/a/-/i/). MMR
      was recorded in response to a standard vowel, /a/, (probability 85%), and to a
      deviant vowel, /i/, (probability of 15%). A priori comparisons included: age,
      sex, and sleep state. These were conducted separately for each of the three
      bandpass filter settings were compared (1-18, 1-30, and 1-40 Hz). RESULTS: A
      priori tests revealed no differences in MMR or ACC for age, sex, or sleep state
      for any of the three filter settings. ACC and MMR responses were prominently
      observed in all 44 sleeping infants (data from four infants were excluded).
      Significant differences observed for ACC were to the onset and offset of stimuli.
      However, neither group nor individual differences were observed to changes in
      speech stimuli in the ACC. MMR revealed two prominent peaks occurring at the
      stimulus onset and at the stimulus offset. Permutation t-tests revealed
      significant differences between the standard and deviant stimuli for both the
      onset and offset MMR peaks (p < 0.01). The 1-18 Hz filter setting revealed
      significant differences for all participants in the MMR paradigm. CONCLUSION:
      Both ACC and MMR responses were observed to auditory stimulation suggesting that
      infants perceive and process speech information even during sleep. Significant
      differences between the standard and deviant responses were observed in the MMR,
      but not ACC paradigm. These findings suggest that the MMR is sensitive to
      detecting auditory/speech discrimination processing. SIGNIFICANCE: This paper
      identified that MMR can be used to identify discrimination in normal hearing
      infants. This suggests that MMR has potential for use in infants with hearing
      loss to validate hearing aid fittings.

PMID- 29635101
TI  - Control of Aspergillus carbonarius in grape berries by Lactobacillus plantarum: A
      phenotypic and gene transcription study.
AB  - The in vitro and in situ antifungal activity of Lactobacillus plantarum against
      the ochratoxigenic fungus Aspergillus carbonarius was investigated in this study.
      Four different fungal isolates from grape berries were co-cultured with four
      different strains of L. plantarum on Malt Extract Agar (MEA) plates at 30 
      degrees C. Bacterial strains inhibited fungal growth up to 88% and significantly
      reduced toxin production up to 100%. In addition, L. plantarum was evaluated as
      biocontrol agent against A. carbonarius growth and OTA production on table
      grapes. Temporal studies of bacterial antagonism were performed with two
      different grape cultivars. Artificially wounded and unwounded berries were pre
      treated with 108 CFU/mL bacteria and inoculated with 106 spores/mL of A.
      carbonarius ochratoxigenic isolates. Biocontrol agents displayed high rate of
      colonization on grapes during 5 days of incubation at 30  degrees C. Scanning
      electron microscopy (SEM) also determined the presence of microorganisms on grape
      surface. Bacterial strains were effective in controlling fungal infection
      reaching up to 71% inhibition rates. However the presence of wounds on grape skin
      facilitated infection of berries by A. carbonarius, since unwounded berries
      showed lower levels of infection. Results also revealed significant reduction in
      mycotoxin production ranging between 32% and 92%. Transcriptome analysis
      following exposure to co-cultivation, exhibited differential expression for each
      gene studied of AcOTAnrps (Aspergillus carbonarius OTA nonribosomal), AcOTApks
      (Aspergillus carbonarius OTA polyketide synthase) and laeA, emphasizing the
      significance of strain variability. The genes AcOTAnrps and laeA were most
      influenced by the presence of L. plantarum. This work is a contribution for the
      potential biocontrol of toxigenic fungi in table grapes by lactic acid bacteria
      (LAB). The above findings underline the significance of bacterial strain
      variability on the effectiveness of biopreservative features of L. plantarum
      strains.

PMID- 29635100
TI  - Eyeball pressure stimulation induces subtle sympathetic activation in patients
      with a history of moderate or severe traumatic brain injury.
AB  - OBJECTIVE: After traumatic brain injury (TBI), there may be persistent central
      autonomic-network (CAN) dysfunction causing cardiovascular-autonomic
      dysregulation. Eyeball-pressure-stimulation (EPS) normally induces cardiovagal
      activation. In patients with a history of moderate or severe TBI (post-moderate
      severe-TBI), we determined whether EPS unveils cardiovascular-autonomic
      dysregulation. METHODS: In 51 post-moderate-severe-TBI patients (32.7 +/- 10.5
      years old, 43.1 +/- 33.4 months post-injury), and 30 controls (29.1 +/- 9.8
      years), we recorded respiration, RR-intervals (RRI), systolic and diastolic blood
      pressure (BPsys, BPdia), before and during EPS (120 sec; 30 mmHg), using an
      ocular-pressure-device (Okulopressor(r)). We calculated spectral-powers of mainly
      sympathetic low (LF: 0.04-0.15 Hz) and parasympathetic high (HF: 0.15-0.5 Hz)
      frequency RRI-fluctuations, sympathetically mediated LF-powers of BPsys, and
      calculated normalized (nu) LF- and HF-powers of RRI. We compared parameters
      between groups before and during EPS by repeated-measurement-analysis-of-variance
      with post-hoc analysis (significance: p < 0.05). RESULTS: At rest,
      sympathetically mediated LF-BPsys-powers were significantly lower in the patients
      than the controls. During EPS, only controls significantly increased RRIs and
      parasympathetically mediated HFnu-RRI-powers, but decreased LF-RRI-powers, LFnu
      RRI-powers, and LF-BPsys-powers; in contrast, the patients slightly though
      significantly increased BPsys upon EPS, without changing any other parameter.
      CONCLUSIONS: In post-moderate-severe-TBI patients, autonomic BP-modulation was
      already compromised at rest. During EPS, our patients failed to activate
      cardiovagal modulation but slightly increased BPsys, indicating persistent CAN
      dysregulation. SIGNIFICANCE: Our findings unveil persistence of subtle
      cardiovascular-autonomic dysregulation even years after TBI.

PMID- 29635102
TI  - Facile one-pot hydrothermal synthesis of cubic spinel-type manganese
      ferrite/biochar composites for environmental remediation of heavy metals from
      aqueous solutions.
AB  - This study reports the facile synthesis of cubic spinel-type manganese ferrite
      (MnFe2O4)/biochar (MF/BC) composites via a one-pot hydrothermal technique.
      Multiple characterizations demonstrated that the MnFe2O4 spinel nanoparticles
      were successfully grown on the biochar, which provides magnetic separability with
      superparamagnetic behavior and effective adsorption performance for heavy metals
      (Pb(II), Cu(II), and Cd(II)). The adsorption kinetics and isotherms can be well
      described with a pseudo-second-order and Sips isotherm models, respectively.
      Comparative adsorption in multi-heavy metal systems (binary and ternary)
      indicated that the adsorption affinity of MF/BC composites toward heavy metals
      followed the sequence of Pb(II) > Cu(II) > Cd(II), which followed the order of
      their covalent indexes. Thermodynamic analysis revealed that the adsorption
      process was endothermic and primarily governed by physisorption. This study
      provides a feasible and simple approach for the preparation of high-performance
      materials for the remediation of heavy metal-contaminated wastewater in a cost
      effective manner.

PMID- 29635103
TI  - Effective cancer immunotherapy based on combination of TLR agonists with
      stimulation of phagocytosis.
AB  - Immunotherapy emerges as a fundamental approach in cancer treatment. Up to date,
      the efficacy of numerous different immunotherapies has been evaluated. The use of
      microorganisms or their parts for immune cell activation, referred to as Pathogen
      Associated Molecular Patterns (PAMPs), represents highly promising concept. The
      therapeutic effect of PAMPs can be further amplified by suitable combination of
      different types of PAMPs such as Toll like receptor (TLR) agonists and
      phagocytosis activating ligands. Previously, we used the combination of
      phagocytosis activating ligand (mannan) and mixture of TLR agonists (resiquimod
      (R-848), poly(I:C), inactivated Listeria monocytogenes) for successful treatment
      of melanoma in murine B16-F10 model. In the present study, we optimized the
      composition and timing of previously used mixture. Therapeutic mixture based on
      well-defined chemical compounds consisted of mannan anchoring to tumor cell
      surface by biocompatible anchor for membranes (BAM) and TLR agonists resiquimod,
      poly(I:C), and lipoteichoic acid (LTA). The optimization resulted in (1)
      eradication of advanced stage progressive melanoma in 83% of mice, (2)
      acquisition of resistance to tumor re-transplantation, and (3) potential anti
      metastatic effect. After further investigation of mechanisms, underlying anti
      tumor responses, we concluded that both innate and adaptive immunity are
      activated and involved in these processes. We tested the efficacy of our
      treatment in Panc02 murine model of aggressive pancreatic tumor as well.
      Simultaneous application of agonistic anti-CD40 antibody was necessary to achieve
      effective therapeutic response (80% recovery) in this model. Our results suggest
      that herein presented immunotherapeutic approach is a promising cancer treatment
      strategy with the ability to eradicate not only primary tumors but also
      metastases.

PMID- 29635104
TI  - Generation and validation of murine monoclonal and camelid recombinant single
      domain antibodies specific for human pancreatic glycoprotein 2.
AB  - Pancreatic secretory zymogen-granule membrane glycoprotein 2 (GP2) has been
      identified as a major autoantigenic target in Crohn's disease patients. It was
      reported recently that a long (GP2a) and a short (GP2b) isoform of GP2 exist and
      that in the outcome of inflammatory bowel diseases (IBD) GP2-specific
      autoantibodies probably appear as new serological markers for diagnosis and
      therapeutic monitoring. To investigate this further and in order to establish
      diagnostic tools for the discrimination of both GP2 isoforms, a set of different
      murine monoclonal and camelid recombinant single domain antibodies (camelid VHH)
      was generated and validated in various enzyme-linked immunosorbent assay (ELISA)
      formats, immunofluorescence on transgenic cell lines and immunohistochemistry on
      monkey pancreas tissue sections. Out of six binders identified, one was validated
      as highly specific for GP2a. This murine monoclonal antibody (mAb) was used as
      capture antibody in construction of a sandwich ELISA for the detection of GP2a.
      Camelid VHHs or a second murine mAb served as detection antibodies in this
      system. All antibodies were also able to stain GP2a or GP2b on transgenic cell
      lines as well as on pancreatic tissue in immunohistochemistry. The KD values
      measured for the camelid VHHs were between 7 nM and 23pM. This set of specific
      binders will enable the development of suitable diagnostic tools for GP2-related
      studies in IBD.

PMID- 29635105
TI  - Topographic and microscopic anatomical description of the emissary sinus of
      foramen ovale in adult humans.
AB  - OBJECTIVE: Although the Emissary Sinus of Foramen Ovale (ESFO) was first
      described by Trolard in 1868, its definition remains confused and neglected in
      the medical literature. This structure represents a vein, two veins, a venous
      plexus, or a dural sinus? Does it really exist? To understand this topic, this
      work aimed to describe the anatomy, topography, and microscopic features of the
      ESFO, precisely characterizing its structure, routes and anatomical correlations.
      PATIENTS AND METHODS: ESFO from the skull's base of adults were dissected into
      fifty anatomical blocks and evaluated using Hematoxylin and Eosin, Picro-sirius
      red and Weigert staining, and by Scanning Electron Microscopy (SEM). RESULTS:
      ESFO was always present between cavernous sinus and pterygoid plexus on both
      antimeres, its inferior route passing through the foramen ovale and/or sphenoidal
      emissary foramen (foramen of Vesalius), anterior to the mandibular branch of
      trigeminal nerve. Its microscopic arrangement resembled what was found on
      transverse sinus, that is composed by layers of collagen fibers oriented on
      transversal and longitudinal planes. It wasn't possible to identify the media and
      adventitial tunica, features seen in veins, and the elastic layer was very thin
      near its lumen. SEM analysis showed that, like the transverse sinus, the ESFO was
      composed by parallel cells that presented a rhombus shape containing central
      rounded nuclei. CONCLUSION: In summary, the venous channel passing through the
      foramen ovale and/or sphenoidal emissary foramen (foramen of Vesalius) is a dural
      venous sinus constituted by dura mater layers and should be considered during
      surgical approaches near the foramen ovale in the middle cranial fossa.

PMID- 29635106
TI  - The finding of a new heterozygous mutation site of the SCN2A gene in a
      monozygotic twin family carrying and exhibiting genetic epilepsy with febrile
      seizures plus (GEFS+) using targeted next-generation sequencing.
AB  - OBJECTIVES: Generalized epilepsy with febrile seizures plus (GEFS+) is a new
      epilepsy syndrome named by the International League Against Epilepsy (ILAE) in
      2001. The SCN2A gene encoding alpha2 subunit of the neuronal sodium channel has
      been reported to be associated with BFNIS, GFES+, Dravet syndrome and some
      intractable childhood epilepsies. This study aimed to develop an approach based
      on next-generation sequencing to determine the genetic defects in a monozygotic
      twin family with GEFS+. PATIENTS AND METHODS: We collected a twin family with
      GEFS+. The DNA of the twin patients was extracted from their peripheral venous
      whole blood. A total of 308 known genes related to epilepsies were selected for
      deep exon resequencing. The patients family's DNA was sequenced through Sanger's
      sequencing for expanded validation. Through systematic data analysis using
      established bioinformatics pipeline and segregation analysis techniques, a number
      of genetic variants were released. RESULTS: Through detailed data analysis, we
      found a new heterozygous mutation c.1399G > A on exon11 of SCN2A (Nav1.2) which
      has not been reported in the HGMD (Human Gene Mutation Database), in the twin
      patients. Then we tested and verified the presence of the same mutation site in
      all individuals of the family. Asymptomatic individuals of this family didn't
      show this mutation. CONCLUSION: The methodology provides a reliable strategy for
      routine gene diagnosis of GEFS+. This observation of a potentially pathogenic
      mutation of SCN2A (Nav1.2) indicates that this gene should be further evaluated
      in order to determine possible routes of causation of GEFS+.

PMID- 29635107
TI  - Cytokine induced killer cells-assisted delivery of chlorin e6 mediated self
      assembled gold nanoclusters to tumors for imaging and immuno-photodynamic
      therapy.
AB  - The cytotoxicity and unique tumor-tropic properties of cytokine-induced killer
      (CIK) cells render them promising in the field of cancer immunotherapy and
      delivery systems. Here, we report a novel and facile approach to assemble gold
      nanoclusters (GNCs) into stable and monodispersed nanoparticles (NPs) using
      Chlorin e6 (Ce6) molecules. Notably, the fluorescence intensity of the GNCs-Ce6
      NPs was about 4.5 folds stronger than the GNCs counterparts. The as-prepared GNCs
      Ce6 NPs were conjugated with CD3 antibody (Ab) and further employed to label CIK
      cells to create a CIK cell-based drug delivery system (Ce6-GNCs-Ab-CIK). The Ce6
      GNCs-Ab-CIK exhibited high tumor-targeting efficiency and excellent therapeutic
      efficacy toward MGC-803 tumor-bearing mice. Benefiting from the synergistic
      therapeutic effect between GNCs-Ce6-Ab NPs and CIK cells, the GNCs-Ce6-Ab-CIK
      strategy may present an ideal cancer theranostic platform for tumor targeted
      imaging and combination therapy.

PMID- 29635108
TI  - In situ formation of interpenetrating polymer network using sequential thermal
      and click crosslinking for enhanced retention of transplanted cells.
AB  - Injectable hydrogels, which are used as scaffolds in cell therapy, provide a
      minimally invasive strategy to enhance cell retention and survival at injection
      site. However, till now, slow in situ gelation, undesired mechanical properties,
      and weak cell adhesion characteristics of reported hydrogels, have led to
      improper results. Here, we developed an injectable fully-interpenetrated polymer
      network (f-IPN) by integration of Diels-Alder (DA) crosslinked network and
      thermosensitive injectable hydrogel. The proposed DA hydrogels were formed in a
      slow manner showing robust mechanical properties. Interpenetration of
      thermosensitive network into DA hydrogel accelerated in situ gel-formation and
      masked the slow reaction rate of DA crosslinking while keeping its unique
      features. Two networks were formed by simple syringe injection without the need
      of any initiator, catalyst, or double barrel syringe. The DA and f-IPN hydrogels
      showed comparable viscoelastic properties along with outstanding load-bearing and
      shape-recovery even under high levels of compression. The subcutaneous
      administration of cardiomyocytes-laden f-IPN hydrogel into nude mice revealed
      high cell retention and survival after two weeks. Additionally, the
      cardiomyocyte's identity of retained cells was confirmed by detection of human
      and cardiac-related markers. Our results indicate that the thermosensitive
      covalent networks can open a new horizon within the injection-based cell therapy
      applications.

PMID- 29635110
TI  - Infants learn a rule predicated on the relation same but fail to simultaneously
      learn a rule predicated on the relation different.
AB  - In two experiments, we assessed whether infants are able to learn rules
      predicated on two abstract relations linked by negation: same and different (not
      same). In an anticipatory looking paradigm, the relation between successive
      colored geometrical shapes predicted the location where a puppet would appear
      next. In Experiment 1, 7-month-olds learned and generalized a rule predicated on
      the relation same, but not a rule predicated on the relation different.
      Similarly, in Experiment 2, 12-month-olds learned a rule predicated on the
      relation same-shape, but not a rule predicated on the relation different-shape.
      Comparing our data with that from previous experiments in the speech domain, we
      found no effect of age, modality or rule complexity. We conclude that, in the
      first year of life, infants already possess a representation of the abstract
      relation same, which serves as input to a rule. In contrast, we find no evidence
      that they represent the relation different.

PMID- 29635109
TI  - Ion channelopathies of the immune system.
AB  - Ion channels and transporters move ions across membrane barriers and are
      essential for a host of cell functions in many organs. They conduct K+, Na+ and
      Cl-, which are essential for regulating the membrane potential, H+ to control
      intracellular and extracellular pH and divalent cations such as Ca2+, Mg2+ and
      Zn2+, which function as second messengers and cofactors for many proteins.
      Inherited channelopathies due to mutations in ion channels or their accessory
      proteins cause a variety of diseases in the nervous, cardiovascular and other
      tissues, but channelopathies that affect immune function are not as well studied.
      Mutations in ORAI1 and STIM1 genes that encode the Ca2+ release-activated Ca2+
      (CRAC) channel in immune cells, the Mg2+ transporter MAGT1 and the Cl- channel
      LRRC8A all cause immunodeficiency with increased susceptibility to infection.
      Mutations in the Zn2+ transporters SLC39A4 (ZIP4) and SLC30A2 (ZnT2) result in
      nutritional Zn2+ deficiency and immune dysfunction. These channels, however, only
      represent a fraction of ion channels that regulate immunity as demonstrated by
      immune dysregulation in channel knockout mice. The immune system itself can cause
      acquired channelopathies that are associated with a variety of diseases of
      nervous, cardiovascular and endocrine systems resulting from autoantibodies
      binding to ion channels. These autoantibodies highlight the therapeutic potential
      of functional anti-ion channel antibodies that are being developed for the
      treatment of autoimmune, inflammatory and other diseases.

PMID- 29635111
TI  - Characterizing conditioned reactivity to sequential alcohol-predictive cues in
      well-trained rats.
AB  - Implicit learning about antecedent stimuli and the unconditional stimulus (US)
      properties of alcohol may facilitate the progressive loss of control over
      drinking. To model this learning, Cofresi et al. (2017) developed a procedure in
      which a discrete, visual conditional stimulus (houselight illumination; CS)
      predicted the availability of a retractable sipper that rats could lick to
      receive unsweetened alcohol [Alcoholism: Clinical and Experimental Research, 41,
      608-617]. Here we investigated the possibility that houselight illumination,
      sipper presentation, and oral alcohol receipt might each exert control over
      alcohol seeking and drinking. We also determined the relationship between
      ingested dose and blood alcohol concentration, in order to validate the idea that
      the US is a post-ingestive action of alcohol. Finally, we tested a major
      prediction from the conditioning account of problematic drinking [Tomie, A., &
      Sharma, N. (2013). Current Drug Abuse Reviews, 6, 201-219], which is that once
      learned, responses elicited by a CS will promote drinking. We found that despite
      having constrained opportunities to drink alcohol during the conditioning
      procedure, ingested doses produced discriminable blood concentrations that
      supported cue conditioning. Based on our analysis of the dynamics of cue
      reactivity in well-trained rats, we found that houselight illumination triggered
      conditioned approach, sipper presentation evoked licking behavior, and alcohol
      receipt promoted drinking. Reactivity to these cues, which varied in terms of
      their temporal proximity to the alcohol US, persisted despite progressive
      intoxication or satiety. Additionally, rats with the greatest conditioned
      reactivity to the most distal alcohol cue were also the fastest to initiate
      drinking and drank the most. Our findings indicate that the post-ingestive
      effects of alcohol may condition multiple cues simultaneously in adult rats, and
      these multiple cues help to trigger alcohol seeking and drinking. Moreover,
      identification and characterization of these cues should be helpful for designing
      interventions that attenuate the power of these cues over behavior.

PMID- 29635112
TI  - Underdiagnosed and disfiguring - Radiation-induced morphea following breast
      cancer treatment.
AB  - OBJECTIVES: Radiation-induced morphea (RIM) is a rare, painful and disfiguring
      complication in women who receive adjuvant radiotherapy treatment for breast
      cancer. It is a distinct entity unrelated to radiation-induced fibrosis of the
      breast. MATERIALS AND METHODS: Between the years 2005-2016, approximately 12,000
      breast cancer cases were treated with surgery and radiation in the central
      district of Israel. From that population, we have identified and managed the
      cases of breast RIM by a multidisciplinary team of dermatologists, breast
      surgeons, and plastic surgeons. Demographic, oncologic, diagnostic and treatment
      data were collected and reviewed. RESULTS: Three cases of breast radiation
      induced morphea, with an estimated prevalence of 1:3000 cases of post-breast
      cancer radiation where identified. The first signs of morphea appeared years
      after the completion of standard RT. Early management leads to superior cosmetic
      results. CONCLUSIONS: Unfortunately, there are no known predictors for RIM. Early
      recognition by the oncologist, the breast surgeon or the reconstructive surgeon
      during follow-up enables expeditious provision of patient reassurance and helps
      guide potential treatment options.

PMID- 29635113
TI  - Multifaceted structures and mechanisms of ABC transport systems in health and
      disease.
AB  - ATP-binding cassette (ABC) transporters are found in all domains of life and
      constitute one of the largest protein superfamilies. ABC transporters harness the
      energy of ATP binding and hydrolysis to shuttle a diverse range of substrates
      across cell membranes. While higher-resolution structures of ABC transporters
      have so far exclusively been obtained by X-ray crystallography, recent advances
      in single-particle cryogenic electron microscopy (cryo-EM) have provided a deluge
      of exciting new structures of medically relevant bacterial and human ABC
      proteins, including those of the cystic fibrosis transmembrane conductance
      regulator (CFTR), and of supramolecular assemblies involving ABC transporters,
      like the ATP-sensitive potassium (KATP) channel and the peptide-loading complex
      (PLC), which is crucially involved in the presentation of antigens in adaptive
      immunity.

PMID- 29635114
TI  - Gene expression profile associated with postnatal development of pyramidal
      neurons in the human prefrontal cortex implicates ubiquitin ligase E3 in the
      pathophysiology of schizophrenia onset.
AB  - Schizophrenia is a neurodevelopmental disorder with the typical age of onset of
      overt symptoms and deficits occurring during late adolescence or early adulthood,
      coinciding with the final maturation of the cortical network involving the
      prefrontal cortex. These observations have led to the hypothesis that
      disturbances of the developmental events that take place in the prefrontal cortex
      during this period, specifically the remodeling of synaptic connectivities
      between pyramidal neurons, may contribute to the onset of illness. In this
      context, we investigated the gene expression changes of pyramidal neurons in the
      human prefrontal cortex during normal periadolescent development in order to gain
      insight into the possible molecular mechanisms involved in synaptic remodeling of
      pyramidal neuronal circuitry. Our data suggest that genes associated with the
      ubiquitination system, which has been implicated in the biology of synaptic
      plasticity, may play a major role. Among these genes, UBE3B, which encodes the
      ubiquitin ligase E3, was found to undergo periadolescent increase and was
      validated at the protein level to be upregulated during periadolescent
      development. Furthermore, we found that the density of UBE3B-immunoreactive
      pyramidal neurons was decreased in schizophrenia subjects, consistent with the
      result of a previous study of decreased UBE3B mRNA expression in pyramidal
      neurons in this illness. Altogether these findings point to the novel hypothesis
      that this specific ligase may play a role in the developmental pathogenesis of
      schizophrenia onset by possibly altering the synaptic remodeling process.

PMID- 29635115
TI  - Comparison of familial and non-familial suicidal behaviors among people with
      major depressive disorder: Testing the discriminative predicting role of high
      yield clinical variables.
AB  - BACKGROUND: Suicidal behavior in first-degree relatives of people diagnosed with
      major depressive disorder (MDD) increases the risk of suicidal behavior. Such an
      effect may be the result of genetic risk factors or environmental ones, including
      imitation, or both. Surprisingly few studies have examined this question and
      thus, there still is little known about the effect of first-degree family history
      of suicidal behavior on the type of suicidal behavior and profile of risk factors
      related to the diathesis for suicidal behavior. Even less is known about intra
      familial risk transmission. METHODS: Patients with MDD (n = 252) experiencing a
      current major depressive episode and who had a previous suicide attempt were
      studied. Those with and without a family history of first-degree relatives who
      had made a suicide attempt or died by suicide were compared across clinical and
      suicide-related characteristics. RESULTS: Suicide attempters with (FDR+, n = 59)
      and without a first-degree relative with suicide attempt or suicide (FDR-, n =
      193) were similar in terms of type or frequency of suicide attempts, level of
      lifetime aggression and impulsivity, age of onset of depression and age at first
      suicide attempt. LIMITATIONS: Cross-Sectional study. Lack of additional external
      validators. CONCLUSIONS: Contrary to our hypothesis and the concept of "genetic
      anticipation", a first-degree family history of suicide attempt or suicide in
      currently depressed attempters with MDD was not associated with a range of
      clinical and suicide-related characteristics. Longitudinal studies incorporating
      external validators and potential biological markers may advance this area of
      research.

PMID- 29635116
TI  - Investigating the awareness, behavior, and attitude toward epilepsy among
      university students in Benghazi, Libya.
AB  - OBJECTIVE: The aim of this study was to explore the level of knowledge regarding
      epilepsy and attitudes prevalent toward people with epilepsy (PWE) among Libyan
      university students in comparison with international data. METHODS: A self
      administrated questionnaire on awareness regarding epilepsy and behaviors toward
      PWE was distributed among undergraduate students enrolled in the University of
      Benghazi. The collected data were analyzed against responses from an Italian
      survey that utilized a similar questionnaire to explore epilepsy-related
      knowledge and attitudes among Italian university students in Rome (Mecarelli et
      al., 2007). RESULTS: Out of the 500 interviewed students, 96% successfully
      completed the survey. Further, 96.6% asserted that they possessed some knowledge
      regarding epilepsy, gained mainly from their families (76.6%). A total of 57.5%
      considered epilepsy to be a psychiatric disorder while 11.6% recommended
      psychological tests for the diagnosis of epilepsy. Moreover, 37.5% believed in
      ancient superstitions, such as possession by evil forces, as the underlying cause
      of the condition, and 31.8% recommended traditional remedies to cure it. Further,
      66.6% deemed epilepsy as a barrier for career prospects, 41% indicated that it
      presents an impediment in participation in sports, and 35% considered it as an
      obstacle in marriage. Additionally, epilepsy was perceived as a severe illness by
      53.3% of the respondents and considered to be a moderately severe condition by
      43.7%. The responses were found to be statistically significant (P<0.05) against
      the responses from the Italian study. CONCLUSION: There is a reasonable level of
      awareness regarding epilepsy among Libyan students, though a lack of accuracy in
      the acquired knowledge exists. The ancient misconceptions regarding the nature of
      epilepsy and negative attitudes toward PWE appear to be rather common among the
      Libyan students. Consequently, the discrepancies in the views between the two
      surveys concerning the ways in which epilepsy is perceived and PWE are treated
      were extremely evident, thus reflecting the already established view that
      epilepsy faces greater stigma as a health condition in developing countries in
      comparison with Western nations.

PMID- 29635119
TI  - From competition to compassion: A caregiving approach to intervening with
      appearance comparisons.
AB  - This study used a novel intervention grounded in social mentalities theory to
      compare the effects of cultivating a caregiving versus competitive mentality when
      intervening with appearance comparisons. For 48 hours, 120 female undergraduates
      were randomly assigned to use one of three strategies whenever they made
      unfavorable appearance comparisons: cultivating compassion and loving-kindness
      toward the comparison target (Caregiving); comparing themselves favorably to the
      target in non-appearance domains of superiority (Competition); or distracting
      themselves (Control). Although there was no main effect of condition, trait
      social comparison orientation interacted with condition to predict outcomes.
      Among women engaging more frequently in social comparison, the Caregiving
      condition was more effective than the Competition condition at reducing body
      dissatisfaction, restrained eating, and body, eating, and exercise-related
      comparisons. Findings suggest that cultivating a compassion-focused, caregiving
      mentality when threatened by appearance comparisons could be beneficial to women
      who engage more frequently in social comparison.

PMID- 29635117
TI  - Highly sensitive label-free amperometric immunoassay of prostate specific antigen
      using hollow dendritic AuPtAg alloyed nanocrystals.
AB  - Herein, well-defined hollow dendritic AuPtAg alloyed nanocrystals (ANCs) were
      synthesized by a simple L-proline-mediated one-pot aqueous method. More
      importantly, the synthesized hollow dendritic architectures provide a suitable
      platform for immobilization of anti-prostate specific antigen (PSA). The
      resultant label-free immunosensor exhibited the improved performance for highly
      sensitive detection of PSA based on the enhanced catalytic currents of
      K3[Fe(CN)6] as a signal probe. Impressively, the immunosensor showed the wide
      linear range of 0.05-50 ng mL-1 and low detection limit of 0.017 ng mL-1 under
      optimal conditions for the assay of PSA, couple with the improved stability,
      reproducibility and selectivity. It provides a promising platform for clinical
      research and diagnosis.

PMID- 29635118
TI  - Micro-nano-bio acoustic system for the detection of foodborne pathogens in real
      samples.
AB  - The fast and efficient detection of foodborne pathogens is a societal priority,
      given the large number of food-poisoning outbreaks, and a scientific and
      technological challenge, given the need to detect as little as 1 viable cell in
      25 gr of food. Here, we present the first approach that achieves the above goal,
      thanks to the use of a micro/nano-technology and the detection capability of
      acoustic wave sensors. Starting from 1 Salmonella cell in 25 ml of milk, we
      employ immuno-magnetic beads to capture cells after only 3 h of pre-enrichment
      and subsequently demonstrate efficient DNA amplification using the Loop Mediated
      Isothermal Amplification method (LAMP) and acoustic detection in an integrated
      platform, within an additional 1/2 h. The demonstrated 4 h sample-to-analysis
      time comes as a huge improvement to the current need of few days to obtain the
      same result. In addition, the work presents the first reported Lab-on-Chip
      platform that comprises an acoustic device as the sensing element, exhibiting
      impressive analytical features, namely, an acoustic limit of detection of 2
      cells/MUl or 3 aM of the DNA target and ability to detect in a label-free manner
      dsDNA amplicons in impure samples. The use of food samples together with the
      incorporation of the necessary pre-enrichment step and ability for multiple
      analysis with an internal control, make the proposed methodology highly relevant
      to real-world applications. Moreover, the work suggests that acoustic wave
      devices can be used as an attractive alternative to electrochemical sensors in
      integrated platforms for applications in food safety and the point-of-care
      diagnostics.

PMID- 29635120
TI  - Dual amplification strategy for improved efficiency of forensic DNA analysis
      using NGM DetectTM, NGMTM or GlobalfilerTM kits.
AB  - The new generation of STR amplification kits with improved sensitivity and
      additional genetic markers is designed particularly for analyzing difficult
      traces with a high DNA degradation index, presence of inhibitors and low level of
      DNA. In the new NGM DetectTM kit, modifications including changing the primers'
      sequences and shortening of STR markers are introduced. The quality control
      system (IQCS, IQCL) used to detect DNA degradation and the presence of inhibitors
      in the sample is an additional feature. The purpose of this study was to compare
      the results of analysis of different kinds of typical casework samples obtained
      using NGMTM or GlobalFilerTM kits with those generated using the new NGM DetectTM
      kit. The results indicate that the tested kit is particularly useful for the
      analysis of challenging samples for which incomplete profiles are generated with
      the NGMTM or GlobalFilerTM kits. The increased number of positively typed alleles
      gives better statistical parameters in genetic identification cases. We conclude
      that the NGM DetectTM kit can be recommended for the double amplification
      protocol together with the NGM or GlobalFilerTM kits.

PMID- 29635121
TI  - N-Acetylcysteine protects human bronchi by modulating the release of neurokinin A
      in an ex vivo model of COPD exacerbation.
AB  - AIMS: N-Acetylcysteine (NAC) reduces the risk of exacerbation of chronic
      obstructive pulmonary disease (COPD). Although NAC also has anti-inflammatory
      activity, the detailed mechanism leading to its protective role remains to be
      elucidated. We tested the impact of NAC against the effects of lipopolysaccharide
      (LPS) in an ex vivo model of COPD exacerbation, and investigated the role of
      neurokinin A (NKA) in this context. MAIN METHODS: Isolated airways from COPD
      patients were incubated overnight with LPS (100 ng/ml). NAC was tested at
      concentrations resembling the plasma levels elicited by oral administration of
      NAC at 200 mg/day (very low dose), 600 mg/day (low dose) and 1.200 mg/day (high
      dose). KEY FINDINGS: NAC at high concentrations normalized the peroxidase
      activity, H2O2, malondialdehyde (MDA), nitric oxide, glutathione (GSH), total
      antioxidant capacity (TAC), and interleukin 6 (IL-6) (overall change 34.32% +/-
      4.22%, P < 0.05 vs. LPS-treated). NAC at low concentrations modulated peroxidase
      activity, H2O2, MDA, GSH, TAC, and IL-6 (overall change 34.88% +/- 7.39%, P <
      0.05 vs. LPS-treated). NAC at very-low concentrations was effective on peroxidase
      activity, H2O2, GSH, and IL-6 (overall change 35.05 +/- 7.71%, P < 0.05 vs. LPS
      treated). Binary logistic regression analysis indicated that the modulatory
      effect of NAC on NKA levels was associated with a reduction of pro-oxidant
      factors and IL-6, and selectively blocking the NK2 receptor abolished such an
      association. SIGNIFICANCE: This study demonstrates that, along with its well
      known antioxidant activity, the protective effect of NAC against the detrimental
      effect of LPS is due to the modulation of NKA and IL-6 levels.

PMID- 29635123
TI  - MHC class I chain-related A: Polymorphism, regulation and therapeutic value in
      cancer.
AB  - MICA and MICB are stress-induced molecules recognized by NKG2D, one of major
      activation receptors of natural killer (NK) cells. Upon binding to NKG2D, NKG2D
      mediated cytolytic immune response of immune effector cells will be activated
      against virally infected and tumor cells expressing MICA. In the early oncogenic
      development, membrane-bound MICA serves as a key signal to recruit anti-tumor
      immune effectors. Nevertheless, both MICA polymorphic features and its
      dysregulated expression in evolving tumors have resulted in tumor evasion in
      various cancer types. Therefore, in order to reconstitute tumor
      immunosurveilance, it is of great significance that we understand MICA genetics,
      polymorphisms, mechanisms of MICA-associated tumor escape and molecular/cellular
      modulation of MICA. In this review, the MICA-associated co-expression networks
      involving microRNAs (miRNAs) and novel candidate long non-coding RNAs (lncRNAs)
      were also discussed. Given the current importance in the study of MICA gene, this
      review paper focuses on the role of MICA in different cancer types, and
      strategies that we manipulate MICA regulation against tumor proliferation.

PMID- 29635122
TI  - Hinokiflavone induces apoptosis in melanoma cells through the ROS-mitochondrial
      apoptotic pathway and impairs cell migration and invasion.
AB  - Melanoma, the highest degree of malignancy, is one of the most common skin
      tumors. However, there is no effective strategy to treat melanoma in current
      clinical practice. Therefore, it is urgent to find an efficient drug to overcome
      melanoma. Here, the in vitro anticancer effects of a natural product named
      hinokiflavone on three melanoma carcinoma cell lines (human melanoma A375 and CHL
      1 cells, murine melanoma B16-F10 cells) and mechanisms of action were explored.
      The results of MTT assay revealed that hinokiflavone inhibited cell proliferation
      of these cell lines in a dose- and time-dependent manner. Interestingly,
      hinokiflavone showed low toxicity to normal liver cells. Flow cytometry assay and
      EdU incorporation assay indicated that hinokiflavone affected A375 and B16 cells
      survival by inducing apoptosis and blocking cell cycle progression at S phase in
      a concentration-dependent manner. Moreover, hinokiflavone enhanced the reactive
      oxygen species (ROS) and decreased the mitochondrial membrane potential
      obviously. Furthermore, hinokiflavone effectively impaired A375 cells migration
      and invasion, and down-regulated the expression of matrix metalloproteinase (MMP)
      MMP2 and MMP9. The above-mentioned results demonstrated that hinokiflavone could
      be a novel chemotherapeutic agent in melanoma treatment by inhibiting cell
      proliferation, inducing apoptosis and cell cycle arresting and blocking cell
      migration and invasion.

PMID- 29635125
TI  - Nobiletin (NOB) suppresses autophagic degradation via over-expressing AKT pathway
      and enhances apoptosis in multidrug-resistant SKOV3/TAX ovarian cancer cells.
AB  - Chemotherapy could be used as an effective therapeutic treatment for ovarian
      cancer and subsequent peritoneal metastasis. However, the occurrence of drug
      resistance reduced the treatment effect originated from cancer chemotherapy.
      Accumulating evidences indicated the significant role of autophagy in tumor cell
      resistance to chemotherapy. Thus, inhibition of autophagy using natural compounds
      could be a promising candidate to overcome multidrug resistance in human ovarian
      cancer cells. Nobiletin (NOB), a polymethoxyflavonoid found in citrus fruits such
      as Citrus depressa and Citrus reticulate, exhibits a number of bioactivities. In
      the present study, NOB selectively suppressed the growth and proliferation of
      human SKOV3/TAX cells, inducing G0/G1 phase arrest and reducing G2/M phase, along
      with the increase of p53 and p21. In addition, NOB induced significant apoptosis
      in SKOV3/TAX cells through the intrinsic apoptosis pathway, as evidenced by the
      up-regulation of cleaved Caspase-9/-3 and PARP. Further, NOB impaired the
      autophagic degradation in SKOV3/TAX cells, resulting in autophagic flux
      inhibition. Moreover, the impaired autophagic flux enhanced NOB-induced apoptosis
      in SKOV3/TAX cells. Importantly, AKT signaling was activated by NOB, which was
      involved in autophagic degradation and apoptotic cell death. In conclusion, the
      findings here supplied the illustration that NOB could overcome multidrug
      resistance in human ovarian cancer cells through AKT-regulated suppression of
      autophagic degradation.

PMID- 29635126
TI  - The role of long non-coding RNA ANRIL in the carcinogenesis of oral cancer by
      targeting miR-125a.
AB  - Recently, increasing evidence has indicated that lncRNAs may play a critical role
      in the progression of oral cancer (OC). However, whether lncRNA-ANRIL is involved
      in the tumorigenesis of OC remains undetermined. In the present study, ANRIL
      showed significantly higher, while miR-125a showed lower, expression in OC
      tissues and sera than in normal controls. MTT, colony formation, flow cytometry
      analysis, wound-healing, transwell and mice xenograft model assays were used to
      detect the proliferation, migration, and invasion of ARNIL-overexpressing HB56
      cells and ARNIL-knockdown CAL27 cells. The results showed that cell
      proliferation, migration, and invasion were significantly increased by ARNIL
      overexpression and decreased by ARNIL silencing in oral cancer cells.
      Furthermore, we found a negative correlation between ARNIL and miR-125a, and
      ARNIL acts as a miRNA-sponge by directly interacting with miR-125a.

PMID- 29635124
TI  - Phosphoethanolamine induces caspase-independent cell death by reducing the
      expression of C-RAF and inhibits tumor growth in human melanoma model.
AB  - Phosphoethanolamine (PEA) is a fundamental precursor during the biosynthesis of
      cell membranes phospholipids. In the past few years, it has been described as a
      potential antitumor agent. In previous studies, we demonstrated that PEA showed
      antitumor properties in vitro and in vivo in a wide range of tumor cell lines.
      Herein, we showed that PEA possesses cytotoxic properties and notably revealed to
      induce caspase-independent cell death. Of interest, we provided evidence that PEA
      inhibits melanoma cells proliferation through the reduction of C-RAF. Molecular
      docking of PEA evidenced that this compound indeed fits satisfactory in the
      binding site located between the dimers of C-RAF protein with 107,01 A and score
      of -29,62. Also, PEA arrested A2058 cells at G2/M phase in the cell cycle.
      Moreover, cell proliferation, migration and adhesion capacities of A2058 cells
      were also inhibited by PEA. Most importantly, PEA inhibited tumor growth of
      melanoma tumors and prolonged survival rate of mice. Also, PEA induced a
      significant immune response in a syngeneic metastatic melanoma model. Taken
      together, these data indicate that PEA is a promising candidate for future
      developments in cancer field.

PMID- 29635127
TI  - Impact of stress on female reproductive health disorders: Possible beneficial
      effects of shatavari (Asparagus racemosus).
AB  - Stress is deeply rooted in the society and women are frequently exposed to
      psychological, physical and physiological stressors. Psychological stress
      disturbs reproductive health by inducing generation of reactive oxygen species
      (ROS) and thereby oxidative stress (OS). The increased OS may affect physiology
      of ovary, oocyte quality and cause female reproductive health disorders. To
      overcome stress-mediated reproductive health disorders in women, shatavari
      (Asparagus racemosus) is frequently recommended in Ayurvedic system of medicine.
      Although shatavari is one of the major health tonics and most popular rasayana
      drugs to treat reproductive ailments of women, underlying mechanism of shatavari
      action at the level of ovary remains poorly understood. Based on the existing
      studies, we propose that shatavari may improve female reproductive health
      complications including hormonal imbalance, polycystic ovarian syndrome (PCOS),
      follicular growth and development, oocyte quality and infertility possibly by
      reducing OS level and increasing antioxidants level in the body. Further studies
      are required to elucidate the mechanism of shatavari actions at the level of
      ovary and oocyte that directly impacts the reproductive health of women.

PMID- 29635128
TI  - Naringin attenuates MLC phosphorylation and NF-kappaB activation to protect
      sepsis-induced intestinal injury via RhoA/ROCK pathway.
AB  - BACKGROUND: Sepsis is commonly associated with excessive stimulation of host
      immune system and result in multi-organ failure dysfunction. Naringin has been
      reported to exhibit a variety of biological effects. The present study aimed to
      investigate the protective effect of naringin on sepsis-induced injury of
      intestinal barrier function in vivo and in vitro. METHODS: Mice were randomly
      divided into 4 groups named sham (n = 20), CLP + vehicle (n = 20), CLP + NG (30
      mg/kg) (n = 20) and CLP + NG (60 mg/kg) (n = 20) groups. Sepsis was induced by
      cecal ligation and puncture (CLP). H&E staining and transmission electron
      microscopy (TEM) were performed to observe intestinal mucosal morphology. ELISA
      was used to determine the intestinal permeability and inflammatory response in
      vivo and in vitro. Western blot and RhoA activity assay were performed to
      determine the levels of tight junction proteins and the activation of indicated
      signaling pathways. MTT assay was used to determine cell viability. RESULTS:
      Naringin improved survival rate of CLP mice and alleviated sepsis-induced
      intestinal mucosal injury. Furthermore, naringin improved impaired intestinal
      permeability and inhibited the release of TNF-alpha and IL-6, while increased IL
      10 level in CLP mice and lipopolysaccharide (LPS)-stimulated MODE-K cells in a
      dose-dependent manner. Naringin increased the expression of tight junction
      proteins ZO-1 and claudin-1 via RhoA/ROCK/NF-kappaB/MLCK/MLC signaling pathway in
      vivo and in vitro. CONCLUSION: Naringin improved sepsis-induced intestinal injury
      via RhoA/ROCK/NF-kappaB/MLCK/MLC signaling pathway in vivo and in vitro.

PMID- 29635130
TI  - Avicularin reversed multidrug-resistance in human gastric cancer through
      enhancing Bax and BOK expressions.
AB  - 5-Fluorouracil (5-Fu) and cisplatin (DDP) as important therapies in treatment of
      human gastric cancer have been widely determined. However, the therapeutic
      effects are usually hampered due to drug resistance or toxicity at high
      concentrations for application. Avicularin (AL, quercetin-3-alpha-l
      arabinofuranoside), a bio-active flavonol isolated from a number of plants, has
      been reported to display diverse pharmacological properties. In this study, we
      explored the hypothesis by which AL reversed 5-Fu or DDP resistance in gastric
      cancer and the underlying molecular mechanism. Here, in vitro, the drug-resistant
      cancer cells were incubated to AL or DDP alone or the combination of AL and DDP.
      Then, MTT, colony formation, Hoechst 33258, flow cytometry and western blot
      analysis were used to investigate the effects of AL in the regulation of drug
      resistance gastric cancer cells. The results indicated that AL treatment markedly
      re-sensitizes the drug resistant cells (SGC-7901/5-Fu and SGC-7901/DDP) to
      cytotoxicity of 5-Fu or DDP. Molecular mechanism analysis indicated that AL and
      DDP combination treatment enhanced apoptosis in SGC-7901/DDP cells, accompanied
      with the up-regulation of cleaved Caspase-3 and PARP, as well as the activation
      of pro-apoptotic signals, including Bax and BOK. Significantly, down regulation
      of Bax or BOK expressions using Bax siRNA or BOK siRNA decreased the inhibitory
      role of DDP in apoptosis of SGC-7901/DDP cells pretreated with AL, demonstrating
      that AL-reversed DDP resistance was associated with Bax and BOK expression. In
      vivo, AL and DDP combination significantly reduced gastric tumor growth.
      Immunohistochemical analysis indicated that co-treatment of AL and DDP
      significantly induced apoptosis, and reduced tumor cell proliferation in tumor
      tissue samples. Furthermore, we also found that the Bax, BOK, cleaved Caspase-3
      and PARP expression in tumor tissues were highly induced by AL and DDP co
      treatment. Together, our findings may provide a novel combination therapeutic
      strategy in treatment of human gastric cancer.

PMID- 29635129
TI  - Renal protective effect of SGLT2 inhibitor dapagliflozin alone and in combination
      with irbesartan in a rat model of diabetic nephropathy.
AB  - Considering the complementary mechanisms of SGLT2 inhibitors and angiotensin
      inhibitors on kidney, it is postulated that combination of both agents could
      afford greater protection against diabetic renal injury. So, we investigated
      renal protective effects of SGLT2 inhibitor, dapagliflozin, alone and in
      combination with irbesartan in a rat model of diabetic nephropathy. Diabetic
      rats, injected with nicotinamide-streptozotocin, were treated orally for 12 weeks
      with either vehicle, dapagliflozin 2 mg/kg/day, irbesartan 30 mg/kg/day, or
      combination of both drugs; respectively. Biochemical analysis included blood
      glucose, HbA1c, urinary albumin excretion, creatinine clearance, TGF-beta1,
      sRAGE, oxidative markers, and histopathological examination of kidneys. Treatment
      with dapagliflozin, irbesartan, and especially their combination, produced
      significant reduction in albuminuria, improved renal function parameters,
      increased sRAGE level and improved inflammatory and oxidative markers, together
      with amelioration of renal histopathological changes. Beside glycemic control,
      dapagliflozin produced higher sRAGE levels than irbesartan, suggesting that
      inhibition of AGE-RAGE axis is important in its renoprotective action.
      Combination of dapagliflozin and irbesartan produced more remarkable protective
      effects on renal function and structure, than use of either agent alone. It is
      concluded that, combination of SGLT2 inhibitor, dapagliflozin and ARB, irbesartan
      could offer more effective renal protection and represent a promising therapeutic
      option for management of diabetic nephropathy.

PMID- 29635131
TI  - Betaine treatment protects liver through regulating mitochondrial function and
      counteracting oxidative stress in acute and chronic animal models of hepatic
      injury.
AB  - Betaine is a derivative of the amino acid glycine widely investigated for its
      hepatoprotective properties against alcoholism. The protective properties of
      betaine in different other experimental models also have been documented. On the
      other hand, the exact cellular mechanism of cytoprotection provided by betaine is
      obscure. The current study was designed to evaluate the hepatoprotective effects
      of betaine and its potential mechanisms of hepatoprotection in two animal models
      of acute and chronic liver injury. Bile duct ligation (BDL) was used as a model
      of chronic liver injury and thioacetamide (TAA)-induced hepatotoxicity was
      applied as the acute liver injury model. Severe increase in serum markers of
      liver tissue damage along with significant liver tissue histopathological changes
      were evident in both acute and chronic models of hepatic injury. It was also
      found that tissue markers of oxidative stress were significantly increased in BDL
      and TAA-treated animals. Moreover, liver mitochondrial indices of functionality
      were deteriorated in both investigated models. Betaine supplementation (10 and 50
      mg/kg, i.p) ameliorated hepatic injury as judged by decreased liver tissue
      histopathological alterations, a significant decrease in tissue markers of
      oxidative stress, and mitigation of serum biomarkers of hepatotoxicity. On the
      other hand, betaine (10 and 50 mg/kg, i.p) protected hepatocytes mitochondria in
      both chronic and acute models of hepatotoxicity. These data indicate that the
      antioxidative and mitochondria regulating properties of betaine could play a
      primary role in its mechanisms of hepatoprotection.

PMID- 29635132
TI  - Bombesin attenuated ischemia-induced spatial cognitive and synaptic plasticity
      impairment associated with oxidative damage.
AB  - The dysfunction of spatial cognition is a character to various neurological
      disorders and therapeutic strategy. However, it is limited to known risk factors
      clinically so far. Gastrin releasing peptide (GRP) signaling is a neuropeptide
      system mediating emotional memory events. However, the effects of GRP agonist on
      spatial cognition and hippocampal synaptic plasticity are rarely investigated,
      especially in pathologic condition. This study was designed to investigate the
      long-term effects of GRPR agonist, bombesin, against cognitive impairment induced
      by chronic cerebral ischemia in rats and its possible mechanisms. Our results
      revealed that bombesin administration (30 MUg/kg/day, for 14 continuous days)
      significantly protected the cognitive and synaptic plasticity impairments as
      assessed by the Morris water maze and long-term potentiation tests. The mechanism
      studies demonstrated that bombesin significantly alleviated the decreased
      activity of total superoxide dismutase (T-SOD), catalase (CAT) and altered the
      increased the content of malondialdehyde (MDA). Besides, the decreased expression
      of synapse plasticity-related proteins, calcium- calmodulin- dependent protein
      kinase II (CaMKII) and synaptophysin (SYP) in the hippocampus were increased with
      drug treatment. In conclusion, bombesin could protect the oxidative stress and
      expression of proteins, which were important for synaptic plasticity and
      cognitive function impairment induced by chronic cerebral ischemia. Our study is
      presented to provide novel insights into the effects of bombesin on spatial
      learning and memory, which should be further explored as a potential drug in
      disorders involving deficits in cognitive function.

PMID- 29635134
TI  - The long non-coding RNA-DANCR exerts oncogenic functions in non-small cell lung
      cancer via miR-758-3p.
AB  - Long non-coding RNAs (lncRNAs) have been demonstrated to be involved in the
      occurrence and progression of multiple cancers. In this study, we investigated
      the role of the lncRNA DANCR in the development of non-small cell lung cancer
      (NSCLC). First, we found that DANCR was markedly upregulated in NSCLC tumor
      tissues and cell lines compared with related normal controls. The ectopic
      expression of DANCR significantly increased the proliferation, migration and
      invasion of SPC-A1 and NCL-H1299 cells. Furthermore, we investigated whether
      DANCR regulates NSCLC tumor formation in vivo. Subsequently, we concluded that
      DANCR promotes NSCLC cell proliferation, migration and invasion by regulating the
      tumor suppressor miR-758-3p. These results indicated that the DANCR/miR-758-3p
      axis could be a potential target in the treatment of NSCLC.

PMID- 29635133
TI  - Icariside II alleviates oxygen-glucose deprivation and reoxygenation-induced PC12
      cell oxidative injury by activating Nrf2/SIRT3 signaling pathway.
AB  - Cerebral ischemia-reperfusion (I/R) injury is a key contributing factor to the
      pathogenic mechanisms involved in ischemic stroke. The present study was designed
      to explore the effects of icariside II (ICS II) on oxygen-glucose
      deprivation/reoxygenation (OGD/R)-induced PC12 cell oxidative injury. The results
      showed that ICS II ameliorated OGD/R-induced PC12 cell injury at the
      concentrations of 12.5, 25, and 50 MUM, as evidenced by both the increase of cell
      viability and the decrease of LDH leakage from 33.96% +/- 0.48% to 16.78% +/-
      0.78%, 13.12% +/- 0.17%, 12.96% +/- 0.10%, respectively. Moreover, ICS II not
      only attenuated the reactive oxygen species (ROS) from 212.2% +/- 5.45%, 168.6%
      +/- 5.29%, 148.7% +/- 9.37%, 142.7% +/- 7.76%, respectively, but also decreased
      the overproduction of mitochondrial ROS, as well as recovered the mitochondrial
      membrane potential (MMP) from 60.68% +/- 7.90% to 76.71% +/- 2.87%, 93.69% +/-
      4.41%, 95.92% +/- 3.97%, respectively. Furthermore, OGD/R accelerated neuronal
      oxidative injury and apoptosis along with reduced nucleus-Nrf2, NQO-1, HO-1, Bcl
      2 protein expressions, and increased Keap1, Bax and cleaved caspase-3 contents,
      whereas ICS II significantly reversed the abovementioned changes. Interestingly,
      ICS II also restrained the OGD/R-induced decrease in SIRT3 and IDH2 expressions.
      In conclusion, this study indicates that ICS II alleviates OGD/R-induced
      oxidative injury in PC12 cells, and its underlying mechanisms are due to the
      regulation of Nrf2/SIRT3 signaling pathway.

PMID- 29635138
TI  - Time use-economic approaches.
AB  - I describe an economic approach to studying time use. The literature has applied
      this approach to analyzing: differences and changes in work time; the gender
      division of chores; the determinants of the split of time outside work;
      differences in time use and time stress by earnings and household income; how the
      artificial constructs of time zones and summer time affect what people do and
      when they do it; how and why non-work time is used differently by race, gender
      and age; and how people would use non-work time if they had more.

PMID- 29635135
TI  - Green route for synthesis of multifunctional fluorescent carbon dots from Tulsi
      leaves and its application as Cr(VI) sensors, bio-imaging and patterning agents.
AB  - We report a one pot green strategy for the synthesis of carbon dots using tulsi
      leaves and their potential application in sensing of Cr(VI) selectively. The
      detection mechanism is based on the phenomenon called inner filter effect (IFE)
      and a good linear static quenching was observed in the range of 1.6 MUM to 50 MUM
      with a detection limit of 4.5 ppb. The reversible switching in fluorescence has
      been tested and a good recovery in fluorescence was observed up to three
      consecutive cycles upon addition of ascorbic acid as reducing agent. Also the low
      toxicity, high fluorescence and photostabilty of the CDs make them excellent
      imaging and patterning agent. The acid and alkali resistant property of these CDs
      makes it suitable for real sample analysis. The fluorescent CDs were applied for
      successful detection of Cr(VI) in water with spike-recoveries ranging from 93 to
      99%.

PMID- 29635137
TI  - Improvements in the water dispersibility of paclitaxel by complexing with
      synthetic peptides derived from beta-casein.
AB  - Recently, digestive peptides prepared as a casein hydrolysate have been found to
      be an effective dispersant for the poorly water-soluble drug paclitaxel (Ptx). A
      major hydrophobic peptide in the digested peptides was identified as
      YQEPVLGPVRGPFPIIV (PepY) by matrix-assisted laser desorption/ionization time-of
      flight/time-of-flight mass spectrometry with the "LIFT" technique. In the present
      study, three peptides PepY, VVVPPFLQPEVMGVSKV (PepV), and KFQSEEQQQTEDELQDK
      (PepK) were chemically synthesized by Fmoc solid-phase synthesis to compare their
      function as dispersants for Ptx. PepV and PepK are the most hydrophobic and
      hydrophilic peptides, respectively, in the sequence of beta-casein, which are the
      same length as PepY (PepY, PepV, and PepK are abbreviated as Peps). The complex
      between Ptx and Peps (Ptx-Peps) was prepared by mixing an ethanol solution of Ptx
      and an aqueous solution of Peps, followed by lyophilization. The complex with
      PepV, which is estimated to be the most hydrophobic of the peptides, had the
      greatest ability to improve the water dispersibility of Ptx. The water
      dispersibility of the complexes between Ptx and PepY and PepV increased as the
      amount of the peptides increased, whereas PepK was not effective in enhancing the
      dispersibility of Ptx. Furthermore, a peptide mixture obtained from a casein
      hydrolysate [Pep (fraction A)] was more effective for the enhancement of Ptx
      dispersibility than the single peptide PepY. These results suggests that a
      variety of peptides in the casein hydrolysate contribute toward complexation with
      Ptx.

PMID- 29635136
TI  - Synthesis and characterization of zinc-silibinin complexes: A potential bioactive
      compound with angiogenic, and antibacterial activity for bone tissue engineering.
AB  - Zinc silibinin complex [Zn(sil)(H2O)2] and mixed ligand zinc complexes such as
      Zn(silibinin)(phenanthroline) [Zn(sil)(phen)], and Zn(silibinin)(neocuproine)
      [Zn(sil)(neo)] have been synthesized and characterized. The UV-vis spectra of the
      Zn(II) complexes showed a considerable shift in the intra-ligand transition. From
      the IR spectra, it is clear that carbonyl group in the C-ring is involved in the
      metal chelation besides A/C-ring hydroxyl group. Thermal gravimetric analysis
      showed that [Zn(sil)(neo)] has higher thermal stability compared to the other two
      Zn(II) complexes. The potential biological activities of the synthesized
      complexes were studied systematically. In osteoblast differentiation, silibinin
      and Zn-silibinin complexes enhanced osteoblast differentiation at the cellular
      level by increasing calcium deposition and ALP activity, and at molecular level
      increased osteoblast markers include Runx2, type 1 col, ALP and OC mRNAs
      expression. Additionally, Zn-silibinin complexes showed promising effects on
      osteoblast differentiation by regulating miR-590/Smad7 signaling pathway. Among
      the complexes, Zn(sil)(phen) showed more stimulatory effect on osteoblastic
      differentiation. These complexes also exhibited angiogenic property by increasing
      VEGF and Ang 1 expression in mouse MSCs and antibacterial activity against E.
      coli (Gram-negative) and S. aureus (Gram-positive) strains. Thus, the present
      study demonstrated that the Zn-silibinin complexes exhibit great potential as a
      pharmacological agent for bone tissue engineering.

PMID- 29635139
TI  - Bilateral absence of the cruciate ligaments with meniscal dysplasia: Unexpected
      diagnosis in a child with juvenile idiopathic arthritis.
AB  - Bilateral agenesis of the cruciate ligaments is a rare congenital anomaly. We
      report a unique case of a young girl who had congenital short femur and diagnosed
      with polyarticular juvenile idiopathic arthritis (JIA) and later discovered to
      have congenital absence of both anterior and posterior cruciate ligaments and
      meniscal dysplasia in both the knees when MRI was performed at 11 years of age.
      The MRI was performed to evaluate knee laxity and persistent symptoms despite
      medical management and multiple steroid injections for arthritis treatment. This
      patient is one of the youngest with congenital absence of both the cruciate
      ligaments to be treated with ACL reconstruction. We highlight the unique
      radiographic imaging manifestations of congenital cruciate ligament agenesis and
      emphasize the role of MRI to confirm and depict additional intraarticular
      abnormalities.

PMID- 29635140
TI  - Islam and cannabis: Legalisation and religious debate in Iran.
AB  - Iran is currently discussing cannabis and opium regulations, which could bring a
      legalisation of drug consumption through a state supervised system. The article
      engages with the question of cannabis by looking at the legal interpretation of
      religious authorities in the Islamic Republic of Iran. The choice of Iran is
      justified for several reasons: firstly, Iran has a long history of drug use and
      cannabis has been part of the country's intoxicant traditions since times
      immemorial; secondly, the Iranian state is unique in that it combines religious
      exegesis with political machination through official channels; finally, among all
      Middle East and Islamic countries, Iran is at the avant-garde in experimenting in
      the field of drugs policy which makes an excellent case for the study of cannabis
      regulation. The article is the result of a direct engagement with Iran's leading
      Shi'a authorities, the maraje'-e taqlid, 'source of emulation'. The authors
      redacted a list of eight questions (estefta'at) about the status of cannabis in
      Iranian society. It questioned cannabis' legality in Islam, its potential medical
      use, the feasibility of domestic production and other relevant aspects of its
      social-religious life. Based on the responses, the authors analysed the
      difference in opinions among the religious scholars and speculate on the
      possibility of policy reform. Given the dearth of scholarly work about illicit
      drugs in the Islamic world, about which many readers might not be familiar, the
      article opens with an overview of the place of cannabis in the history of Islamic
      societies. It discusses terminological ambiguities, references in religious texts
      and traditions, and the general interpretations within Muslim religious schools
      of thought. Then, it discusses the status of cannabis in contemporary Iran before
      tackling the responses provided by the religious scholars. Eventually, the paper
      puts forward reflections about the potential implications for future policy
      developments on cannabis.

PMID- 29635144
TI  - Bladder cancer survival: Women better off in the long run.
AB  - AIM: Mortality among patients with bladder cancer is usually reported to be
      higher for women than men, but how the risk differs and why remain largely
      unexplained. We also described gender-specific differences in survival for
      patients with bladder cancer and estimated to what extent they can be explained
      by differences in T-stage distribution at the first diagnosis. METHODS: The
      present study comprised all 15,129 new cases of histologically verified invasive
      and non-invasive urothelial carcinoma of the urinary bladder diagnosed between
      1997 and 2011 as registered in the Cancer Registry of Norway. Gender-specific
      excess mortality risk rates and risk ratios were calculated based on a flexible
      parametric relative survival model adjusting for T-stage and age, allowing the
      effect of gender to vary over time. We also present gender-specific relative
      survival curves for different T-stage patterns adjusted for age. RESULTS: Risk
      rates were significantly higher for women than men up to 2 years after bladder
      cancer diagnosis, particularly for muscle-invasive cancers. Thereafter, risk
      rates appeared to be higher in men. Adverse T-Stage distribution in women
      explained half of the unfavourable survival difference in female patients 2 years
      after diagnosis. CONCLUSION: The common view of worse bladder cancer prognosis in
      women than in men needs to be revised. Norwegian women have a less favourable
      prognosis solely within the first 2 years after diagnosis, particularly when
      diagnosed with a muscle-invasive tumour; parts of this discrepancy can be
      attributed to more severe initial diagnoses in women.

PMID- 29635141
TI  - Posterior cervical spine crisscross fixation: Biomechanical evaluation.
AB  - BACKGROUND: Biomechanical/anatomic limitations may limit the successful
      implantation, maintenance, and risk acceptance of posterior cervical plate/rod
      fixation for one stage decompression-fusion. A method of posterior fixation
      (crisscross) that resolves biomechanical deficiencies of previous facet wiring
      techniques and not reliant upon screw implantation has been devised. The
      biomechanical performance of the new method of facet fixation was compared to the
      traditional lateral mass plate/screw fixation method. METHODS: Thirteen human
      cadaver spine segments (C2-T1) were tested under flexion-compression loading and
      four were evaluated additionally under pure-moment load. Preparations were
      evaluated in a sequence of surgical alterations with intact, laminectomy, lateral
      mass plate/screw fixation, and crisscross facet fixation using forces,
      displacements and kinematics. FINDINGS: Combined loading demonstrated
      significantly lower bending stiffness (p < 0.05) between laminectomy compared to
      crisscross and lateral mass plate/screw preparations. Crisscross fixation showed
      a comparative tendency for increased stiffness. The increased overall motion
      induced by laminectomy was resolved by both fixation techniques, with crisscross
      fixation demonstrating a comparatively more uniform change in segmental motions.
      INTERPRETATION: The crisscross technique of facet fixation offers immediate
      mechanical stability with resolution of increased flexural rotations induced by
      multi-level laminectomy. Many of the anatomic limitations and potentially
      deleterious variables that may be associated with multi-level screw fixation are
      not associated with facet wire passage, and the subsequent fixation using a
      pattern of wire connection crossing each facet joint exhibits a comparatively
      more uniform load distribution. Crisscross wire fixation is a valuable addition
      to the surgical armamentarium for extensive posterior cervical single-stage
      decompression-fixation.

PMID- 29635142
TI  - Predictors of etiological beliefs about panic disorder and impact of beliefs on
      treatment outcomes.
AB  - Little is known about the beliefs people with panic disorder (PD) have about
      their illness and how these beliefs might influence treatment outcome. This study
      explored demographic and clinical predictors of etiological beliefs about PD and
      the impact these beliefs have on treatment response. The sample included 251
      outpatients with PD who participated in a randomized placebo-controlled trial of
      treatments for PD. Regression analyses revealed that sex, duration of PD and
      family history of psychiatric illnesses predicted biological etiological beliefs,
      previous history of psychotherapy predicted environmental etiological beliefs,
      and age, impaired functioning, and measures of "fear of fear" predicted multiple
      etiological beliefs about PD. Etiological beliefs predicted more severe symptoms
      at 12 weeks post-treatment, irrespective of the type of treatment received, but
      had no effect on attrition, treatment adherence or treatment-related adverse
      effects This study contributes to the sparse literature on etiological beliefs
      about PD. Results are preliminary and further research is needed to understand
      more fully the factors that shape etiological beliefs about PD, whether these
      beliefs change over the course of illness, and the impact etiological beliefs
      have on treatment outcome.

PMID- 29635143
TI  - Coping styles in individuals at ultra-high risk for psychosis: Associations with
      cognitive appraisals.
AB  - Maladaptive coping may play an important role in the manifestation of symptoms,
      functioning, and overt psychosis onset in individuals at ultra-high risk (UHR)
      for psychosis. To determine the factors associated with coping strategies, the
      relationships between cognitive appraisals and coping styles were investigated in
      UHR individuals. Sixty-five UHR individuals and 83 healthy controls were assessed
      for coping styles and cognitive appraisals of attribution bias as a primary
      appraisal and self-efficacy and perceived social support as a secondary
      appraisal. UHR participants relied more on a passive, tension-reduction coping
      style and less on an active, problem-focused coping style. These maladaptive
      coping styles in UHR individuals were significantly associated with their
      cognitive appraisals of stress. Aberrant attribution style of hostility
      perception and composite blaming bias were associated with problem-focused coping
      and tension-reduction, respectively. Perceived social support was related to
      problem-focused coping, seeking social support, and wishful thinking. General
      self-efficacy was associated with problem-focused coping. Our findings suggest
      that cognitive appraisals themselves may be the major determinants of coping
      styles in UHR individuals. The identified attribution styles, perceived social
      support, and self-efficacy may provide some clues regarding specialized
      interventions for the buildup of adaptive coping strategies in UHR individuals.

PMID- 29635145
TI  - Treatment decisions and the impact of adverse events before and during extended
      endocrine therapy in postmenopausal early breast cancer.
AB  - BACKGROUND: Extended endocrine therapy beyond 5 years for postmenopausal breast
      cancer has been studied within multiple phase III trials. Treatment compliance in
      these trials is generally poor. In this analysis, we aimed to determine factors
      that were associated with participation in the phase III Investigation on the
      Duration of Extended Adjuvant Letrozole (IDEAL) trial and with early treatment
      discontinuation, and how this influenced survival outcome. METHODS: In the IDEAL
      trial, postmenopausal patients were randomised between 2.5 or 5 years of extended
      letrozole, after completing 5 years of endocrine therapy for hormone receptor
      positive early breast cancer. A subgroup of this population participated earlier
      in the Tamoxifen Exemestane Adjuvant Multinational trial (5 years of exemestane
      or 2.5 years of tamoxifen followed by exemestane as primary adjuvant therapy) in
      which we explored which factors were determinative for enrolment in the IDEAL
      study. In the IDEAL cohort, we evaluated which factors predicted for early
      treatment discontinuation and the effect of early treatment discontinuation on
      disease-free survival (DFS). RESULTS: Nodal status, younger age and adjuvant
      chemotherapy were significantly associated with higher enrolment in the IDEAL
      trial. In the IDEAL cohort, adverse events (AEs), the type of primary endocrine
      therapy and the interval between primary and extended therapy were associated
      with early treatment discontinuation. Among the reported AEs, depressive feelings
      (56%) were most frequently associated with early treatment discontinuation. Early
      treatment discontinuation was not associated with worse DFS (hazard ratio [HR] =
      1.02, 95% confidence interval = 0.76-1.37). CONCLUSIONS: In this analysis, we
      found that risk factors were most strongly associated enrolment in the IDEAL
      trial. In contrast, patient experiences were the most significant factors leading
      to early treatment discontinuation, with no effect on DFS.

PMID- 29635146
TI  - Immunotherapy phase I trials in patients Older than 70 years with advanced solid
      tumours.
AB  - BACKGROUND: The development of immune checkpoint blocker development brings new
      hope in older patients (OPs) because of clinical efficacy and low toxicity.
      Clinical indications are rising steadily, but very few data are available in the
      geriatric population where comorbidities, reduced functional reserve and
      immunosenescence may affect efficacy and tolerance. METHODS: All cases of
      patients enrolled in immunotherapy phase I trials between January 2012 and
      December 2016 in the Drug Development Department (DITEP) at Gustave Roussy were
      retrospectively reviewed. Case-control analysis was performed in OPs (patients >=
      70 years) matched to younger patients (YPs) (patients < 70 years) by trial and
      treatment dose. We compared cumulative incidence, grade and type of immune
      related adverse events (IrAEs) and survival outcomes. RESULTS: Among the 46 OPs
      and the 174 YPs enrolled in 14 phase I/II trials, 10 (22%) and 23 (13%) patients
      experienced grade III-IV IrAEs. Cumulative incidence of grade I-II IrAEs was
      significantly higher in OPs than YPs (p < 0.05). No significant difference was
      observed between the two groups for grade III-IV IrAEs (p = 0.50). Older age was
      not associated with lower dose intensity of treatment (p = 0.14). No significant
      difference was observed between OPs and YPs in median progression-free survival
      (hazards ratio 1.41, 95% confidence interval [CI] [0.94-2.11] p = 0.09) or median
      overall survival (HR 0.92, 95% CI [0.61-1.39] p = 0.77). CONCLUSION: Immune
      checkpoint blockade appears to be an acceptable treatment option for OPs in the
      setting of phase I trials.

PMID- 29635148
TI  - Airtraq(r) reduces the hemodynamic response to tracheal intubation using single
      lumen tubes in adults compared with the Macintosh laryngoscope: A systematic
      review and meta-analysis of randomized control trials.
AB  - STUDY OBJECTIVE: To investigate whether Airtraq(r) attenuate the hemodynamic
      responses to tracheal intubation using single-lumen tubes in adults as compared
      with the Macintosh laryngoscope. DESIGN: Meta-analysis. SETTING: Operating room.
      MEASUREMENTS: The primary outcome of this meta-analysis was to determine whether
      laryngoscopy using the Airtraq(r) reduced hemodynamic responses-heart rate (HR)
      and mean blood pressure (MBP)-at 60 s (s) after tracheal intubation compared to
      laryngoscopy with the Macintosh laryngoscope. Pooled differences in these
      hemodynamic responses between the two devices were expressed as weighted mean
      difference with 95% confidence intervals. We then conducted trial sequential
      analysis (TSA). The secondary outcome was to investigate whether the Airtraq(r)
      reduce the hemodynamic response at 120 s, 180 s, and 300 s after tracheal
      intubation compared to the Macintosh laryngoscope. We also conducted sensitivity
      analysis of the hemodynamic responses to tracheal intubation with the
      laryngoscopes using a multivariate random effects model accounting for within
      study correlation of the longitudinal data. MAIN RESULTS: From electronic
      databases, we selected 11 randomized controlled trials for studies that enrolled
      subjects satisfying our inclusion criteria. Compared with the Macintosh
      laryngoscope, the Airtraq(r) significantly reduced both HR and MBP at 60 s after
      tracheal intubation. In secondary outcome, the Airtraq(r) significantly reduced
      both HR and MBP at all measurement points, excluding HR at 300 s after tracheal
      intubation. TSA showed that total sample size reached the required information
      size for both HR and MBP. The sensitivity analysis revealed that the Airtraq(r)
      reduced both HR and MBP at all measurement points, excluding HR at 300 s after
      tracheal intubation. CONCLUSIONS: The Airtraq(r) attenuates the hemodynamic
      response at 60 s after tracheal intubation compared with the Macintosh
      laryngoscope. (GRADE: Low) These results were supported by the sensitivity
      analysis. TSA suggested that the total sample size was exceeded TSA monitoring
      boundary both HR and MBP.

PMID- 29635147
TI  - Phase I feasibility study for intrathecal administration of trastuzumab in
      patients with HER2 positive breast carcinomatous meningitis.
AB  - PURPOSE: Leptomeningeal carcinomatosis (MC) is commonly associated with HER2
      positive breast cancer (HER2-BC), with a poor prognosis and no standardised
      treatment. We conducted a phase I dose-escalation study of intrathecal (IT)
      administration of trastuzumab in HER2-BC patients with MC to determine the
      maximum tolerated dose (MTD), which was based on both the achievement of a
      trastuzumab intra-cerebrospinal fluid concentration close to a conventional
      therapeutic plasma concentration (30 mg/L) and/or dose-limiting toxicity (DLT).
      METHODS: The protocol planned IT administration of trastuzumab (30 mg, 60 mg, 100
      mg or 150 mg dose levels) once a week, over the course of at least 4 weeks.
      Sixteen patients with MC from HER2-BC received IT trastuzumab. Intra
      cerebrospinal fluid samples were obtained before each injection for
      pharmacokinetics. RESULTS: We did not observe DLT of IT trastuzumab. Eleven
      patients had no toxicity attributed to IT trastuzumab. For 60 mg or higher dose
      levels, minor toxicities attributed to IT trastuzumab included headache (2
      patients), nausea (2 patients), vomiting (1 patient), cervical pain (1 patient)
      and peripheral neuropathy (1 patient). Two patients experienced immediate
      toxicity including headache or vomiting. The mean residual intra-cerebrospinal
      fluid concentration of trastuzumab was 27.9 mg/L for the 150 mg dose level. Three
      patients achieved a clinical response, seven patients had stable disease and four
      patients had progressive disease. CONCLUSIONS: The MTD and recommended phase II
      weekly dose of IT trastuzumab in patients with HER2-BC and MC is 150 mg. A phase
      II trial using this dose regimen in MC from HER2-BC is ongoing. REGISTRATION
      IDENTIFICATION: ClinicalTrials.gov Identifier: NCT01373710
      (https://clinicaltrials.gov/ct2/show/NCT01373710?term=trastuzumab+intrathecal&ran
      =1).

PMID- 29635149
TI  - Comparison of the thermal stabilization of proteins by oligosaccharides and
      monosaccharide mixtures: Measurement and analysis in the context of excluded
      volume theory.
AB  - The thermal stability of apo alpha-lactalbumin (alpha-LA) and lysozyme was
      measured in the presence of mixtures of glucose, fructose, and galactose.
      Mixtures of these monosaccharides in the appropriate stoichiometric ratio were
      found to have a greater stabilizing effect on each of the two proteins than equal
      weight/volume concentrations of di- tri- and tetrasaccharides with identical
      subunit composition (sucrose, trehalose, raffinose, and stachyose). The excluded
      volume model for the effect of a single saccharide on the stability of a protein
      previously proposed by Beg et al. [Biochemistry 54 (2015) 3594] was extended to
      treat the case of saccharide mixtures. The extended model predicts quantitatively
      the stabilizing effect of all monosaccharide mixtures on alpha-LA and lysozyme
      reported here, as well as previously published results obtained for ribonuclease
      A [Biophys. Chem. 138 (2008) 120] to within experimental uncertainty.

PMID- 29635150
TI  - Model-based approach for cyber-physical attack detection in water distribution
      systems.
AB  - Modern Water Distribution Systems (WDSs) are often controlled by Supervisory
      Control and Data Acquisition (SCADA) systems and Programmable Logic Controllers
      (PLCs) which manage their operation and maintain a reliable water supply. As
      such, and with the cyber layer becoming a central component of WDS operations,
      these systems are at a greater risk of being subjected to cyberattacks. This
      paper offers a model-based methodology based on a detailed hydraulic
      understanding of WDSs combined with an anomaly detection algorithm for the
      identification of complex cyberattacks that cannot be fully identified by
      hydraulically based rules alone. The results show that the proposed algorithm is
      capable of achieving the best-known performance when tested on the data published
      in the BATtle of the Attack Detection ALgorithms (BATADAL) competition
      (http://www.batadal.net).

PMID- 29635151
TI  - Vertical-algal-biofilm enhanced raceway pond for cost-effective wastewater
      treatment and value-added products production.
AB  - A win-win strategy by the integration of wastewater treatment with value-added
      products production through a vertical-algal-biofilm enhanced raceway was
      investigated in the present study. Raceway pond was enhanced by vertically
      setting the biofilm in the system with a certain interval distance that could be
      adjusted for different light conditions and wastewater types. Two types of
      synthetic wastewater were treated with suitability-proven materials as biofilm
      carriers under four operation distances. Composition of the harvested algal
      biomass was analyzed. Coral velvet with 5-8 mm length villus was the optimal
      carrier, since it was durable and with high biomass productivity (6.95-8.11 g m
      2.day-1). Nutrients in the wastewaters were efficiently removed with the COD, TN
      and TP reduction of over 86.61%, 73.68% and 89.85%, respectively. Wastewater with
      the low nutrients concentration experienced lower biomass and lipid productivity
      but larger biodiesel productivity and higher nutrient removal efficiency. In
      addition, as the operation distance increased, wastewater treatment efficiency
      was first increased but then decreased, while algal biomass footprint production
      was decreased. Differences in nutrients removal efficiencies were mainly due to
      the distance difference, which caused different biofilm culture surface areas and
      light regimes. The optimal operation distance as a function of the efficient
      nutrient removal and biodiesel production in this study was 6 cm.

PMID- 29635152
TI  - Transport of bacteriophage MS2 and PRD1 in saturated dune sand under suboxic
      conditions.
AB  - Soil passage of (pretreated) surface water to remove pathogenic microorganisms is
      a highly efficient process under oxic conditions, reducing microorganism
      concentrations about 8 log10 within tens of meters. However, under anoxic
      conditions, it has been shown that removal of microorganisms can be limited very
      much. Setback distances for adequate protection of natural groundwater may,
      therefore, be too short if anoxic conditions apply. Because removal of
      microorganisms under suboxic conditions is unknown, this research investigated
      removal of bacteriophage MS2 and PRD1 by soil passage under suboxic conditions at
      field scale. At the field location (dune area), one injection well and six
      monitoring wells were installed at different depths along three suboxic flow
      lines, where oxygen concentrations ranged from 0.4 to 1.7 mg/l and nitrate
      concentrations ranged from 13 to 16 mg/L. PRD1 and MS2 were injected directly at
      the corresponding depths and their removal in each flow line was determined. The
      highest bacteriophage removal was observed in the top layer, with about 9 log
      removal of MS2, and 7 log removal of PRD1 after 16 meters of aquifer transport.
      Less removal was observed at 12 m below surface, probably due to a higher
      groundwater velocity in this coarser grained layer. MS2 was removed more
      effectively than PRD1 under all conditions. Due to short travel times,
      inactivation of the phages was limited and the reported log removal was mainly
      associated with attachment of phages to the aquifer matrix. This study shows that
      attachment of MS2 and PRD1 is similar for oxic and suboxic sandy aquifers, and,
      therefore, setback distances used for sandy aquifers under oxic and suboxic
      conditions provide a similar level of safety. Sticking efficiency and the
      attachment rate coefficient, as measures for virus attachment, were evaluated as
      a function of the physico-chemical conditions.

PMID- 29635154
TI  - Vertical up-flow constructed wetlands exhibited efficient antibiotic removal but
      induced antibiotic resistance genes in effluent.
AB  - The intensive use of antibiotics results in their continuous release into the
      environment and the subsequent widespread dissemination of antibiotic resistance
      genes (ARGs), thus posing potential risks for public health. Although vertical up
      flow constructed wetlands (VUF-CWs) have been widely used to treat wastewater in
      remote or rural regions, few studies have assessed the potential risks of ARG
      dissemination when VUF-CWs are applied to treat wastewaters containing
      antibiotics. In this study, the removal performance of two typical antibiotics
      (sulfamethoxazole (SMX) and tetracycline (TC)) and the fate of ARGs were
      evaluated in three lab-scale VUF-CWs. The results indicated that high removal
      efficiencies (>98%) could be achieved for both SMX and TC. However, the exposure
      of antibiotics resulted in harboring abundant ARGs (mainly sul- and tet-related
      genes), even with increasing abundances with operation time. The abundances of
      ARGs had a positive correlation with the accumulation of SMX and TC in different
      layers of VUF-CWs, where the tet and sul genes have the highest abundance in the
      bottom layer due to the highest antibiotic exposure concentration. Positive
      correlations were observed between the abundance of tet gene and antibiotic
      concentration in effluent. Although the effluent had lower abundances of the ARGs
      than that in the wetland media, the occurrence of ARGs in effluent might still
      pose risk for public health. Further studies are required to explore effective
      control strategies to eliminate ARGs from VUF-CWs.

PMID- 29635153
TI  - Effects of phosphate-enhanced ozone/biofiltration on formation of disinfection
      byproducts and occurrence of opportunistic pathogens in drinking water
      distribution systems.
AB  - The effects of ozone-biologically activated carbon (O3-BAC) treatment with
      various phosphate doses (0, 0.3 or 0.6 mg/L) were investigated on the formation
      of disinfection by-products (DBPs) and occurrence of opportunistic pathogens
      (OPs) in drinking water distribution systems (DWDSs) simulated by annular
      reactors (ARs). It was found that the lowest DBPs and the highest inactivation of
      OPs such as Mycobacterium spp., Mycobacterium avium, Aeromonas spp., Pseudomonas
      aeruginosa and Hartmanella vermiformis, occurred in the effluent of the AR with
      0.6 mg/L phosphate addition. Based on the results of different characterization
      techniques, for the AR with 0.6 mg/L phosphate-enhanced O3-BAC treatment,
      dissolved organic carbon in the influent exhibited the lowest concentration and
      most stable fraction due to the improved biodegradation effect. Moreover, the
      total amount of suspended extracellular polymeric substances (EPS) in the bulk
      water of the AR decreased greatly, resulting in the lowest chlorine consumption
      and DBPs formation in the AR. In Fourier transform infrared spectra of the
      suspended EPS, the amide II band (1600-1500 cm-1) disappeared and the
      protein/polysaccharide ratio decreased remarkably, indicating the destruction of
      protein and a decrease in hydrophobicity. Moreover, beta-sheets and alpha-helices
      in the protein secondary structures were degraded while the random coils
      increased sharply as phosphate addition increased to 0.6 mg/L, inhibiting
      microbial aggregation and hence weakening the chlorine-resistance capability.
      Thus, most of the OPs in suspended biofilms were more easily inactivated by
      residual chlorine, resulting in the lowest OPs occurrence in the effluent of the
      AR. Our findings indicated that enhancing the efficiency of the BAC filter by
      adding phosphate is a promising method for improving water quality in DWDSs.

PMID- 29635155
TI  - Synergistic effects in iron-copper bimetal doped mesoporous gamma-Al2O3 for
      Fenton-like oxidation of 4-chlorophenol: Structure, composition, electrochemical
      behaviors and catalytic performance.
AB  - Iron-copper bimetal supported on mesoporous gamma-Al2O3 with different Fe/Cu
      ratios was prepared via a modified evaporation-induced self-assembly method and
      employed to degrade 4-chlorophenol (4-CP) in a Fenton-like process. The X-ray
      photoelectron spectroscopy, X-ray diffraction spectrum and UV-vis diffuse
      reflectance spectroscopy results confirmed the co-doping of Fe2+/Fe3+ and
      Cu+/Cu2+ into the lattice of gamma-Al2O3 through the bonds of AlOFe and AlOCu.
      With the iron and copper co-doped in gamma-Al2O3, three-fold oxygen vacancies
      (V0) could be achieved compared with that of non-metal catalysts, which was
      favorable for the reduction of iron and copper species. The 1Fe3Cu-gamma-Al2O3
      with a Fe/Cu mass ratio of 1:3 exhibited the highest activity on Fenton-like
      degradation of 4-CP due to the synergistic effects of Fe and Cu by facilitating
      the electron transfer in the recycles of Cu+/Cu2+ and Fe2+/Fe3+ based on the
      results of X-ray photoelectron spectroscopy, cyclic voltammetry and electro
      paramagnetic resonance analysis. The utilization efficiency of H2O2 was as high
      as 86.0% when 4-CP almost disappeared (i.e., 99.7 percent of 0.78 mM 4-CP) at 240
      min and pH 7.0, additionally, their dechlorination and TOC removal efficiencies
      were 92.0% and 81.6%, respectively. The catalyst also displayed a good
      performance after 5th cycles. Furthermore, a possible mechanism for activation of
      OH on the catalyst surface was also proposed.

PMID- 29635159
TI  - Temperature-dependent elimination efficiency on Phaeocystis globosa by different
      initial population sizes of rotifer Brachionus plicatilis.
AB  - Due to sea water eutrophication and global warming, the harmful Phaeocystis
      blooms outbreak frequently in coastal waters, which cause a serious threat to
      marine ecosystem. The application of rotifer to control the harmful alga is a
      promising way. To investigate the influence of initial rotifer density and
      temperature on the ability of rotifer Brachionus plicatilis to eliminate
      Phaeocystis globosa population, we cultured P. globosa with different initial
      rotifer densities (1, 3, 5 inds mL-1) at 19, 22, 25, 28, and 31  degrees C for 9
      16 d. Results showed that the population of rotifer feeding on Phaeocystis
      increased rapidly and higher temperatures favored the growth of P. globosa and B.
      plicatilis. With increased initial rotifer density and temperature, both the
      clearance rate of rotifer and the reduction rate of P. globosa increased, and
      thus P. globosa were eliminated earlier. Both temperature and initial rotifer
      density had significant effects on clearance rate of rotifer and the time to
      Phaeocystis extinction, and there was a significant interaction between the two
      factors on the two parameters, i.e., the effect of initial rotifer density on
      eliminating Phaeocystis decreased with increasing temperature. The rotifer in 5
      inds mL-1 at 28  degrees C eliminated P. globosa in 4 d, whereas the rotifer in 1
      ind mL-1 at 19  degrees C spent about 16 d on eliminating P. globosa. In
      conclusion, higher temperature and bigger initial rotifer density promote rotifer
      to eliminate the harmful P. globosa, and the optimal temperature for rotifer to
      clear P. globosa is 28  degrees C.

PMID- 29635156
TI  - Comparative study of Cu-based bimetallic oxides for Fenton-like degradation of
      organic pollutants.
AB  - In order to provide useful information for the rational design of effective
      Fenton-like catalyst, a series of Cu-based bimetallic oxides were synthesized and
      their Fenton-like performances for the degradation of Orange II and ciprofloxacin
      were compared. The structure, chemical oxidation state, surface charge property
      and redox ability of the catalysts were also investigated by different
      characterization techniques. Among them, NiCu exhibited the highest adsorption
      capacity towards Orange II and the highest activity for the production of OH from
      H2O2 decomposition, which could be attributed to its high surface area and highly
      positively charged surface. However, FeCu exhibited the highest activity for the
      degradation of Orange II. The reason might be that FeCu has more unpaired
      electrons and higher redox ability, thus promoting the activation of adsorbed
      Orange II through the electron transfer process. By contrast, NiCu exhibited the
      highest activity for the removal of ciprofloxacin because ciprofloxacin was
      mainly degraded by OH. Finally, the main degradation intermediates of Orange II
      and ciprofloxacin were determined by liquid chromatography-mass spectrometry.

PMID- 29635157
TI  - Achieving mainstream nitrogen removal through simultaneous partial nitrification,
      anammox and denitrification process in an integrated fixed film activated sludge
      reactor.
AB  - The anaerobic ammonium oxidation (anammox) is becoming a critical technology for
      energy neutral in mainstream wastewater treatment. However, the presence of
      chemical oxygen demanding in influent would result in a poor nitrogen removal
      efficiency during the deammonification process. In this study, the simultaneous
      partial nitrification, anammox and denitrification process (SNAD) for mainstream
      nitrogen removal was investigated in an integrated fixed film activated sludge
      (IFAS) reactor. SNAD-IFAS process achieved a total nitrogen (TN) removal
      efficiency of 72 +/- 2% and an average COD removal efficiency was 88%. The
      optimum COD/N ratio for mainstream wastewater treatment was 1.2 +/- 0.2. Illumina
      sequencing analysis and activity tests showed that anammox and denitrifying
      bacteria were the dominant nitrogen removal microorganism in the biofilm and the
      high COD/N ratios (>=2.0) leaded to the proliferation of heterotrophic bacteria
      (Hydrogenophaga) and nitrite-oxidizing bacteria (Nitrospira) in the suspended
      sludge. Network analysis confirmed that anammox bacteria (Candidatus Kuenenia)
      could survive in organic matter environment due to that anammox bacteria
      displayed significant co-occurrence through positive correlations with some
      heterotrophic bacteria (Limnobacter) which could protect anammox bacteria from
      hostile environments. Overall, the results of this study provided more
      comprehensive information regarding the community composition and assemblies in
      SNAD-IFAS process for mainstream nitrogen removal.

PMID- 29635160
TI  - Simultaneous phosphorous and nitrogen recovery from source-separated urine: A
      novel application for fertiliser drawn forward osmosis.
AB  - Re-thinking our approach to dealing with waste is one of the major challenges in
      achieving a more sustainable society. However, it could also generate numerous
      opportunities. Specifically, in the context of wastewater, nutrients, energy and
      water could be mined from it. Because of its exceptionally high nitrogen (N) and
      phosphorous (P) concentration, human urine is particularly suitable to be
      processed for fertiliser production. In the present study, forward osmosis (FO)
      was employed to mine the P and N from human urine. Two Mg2+-fertilisers, i.e.
      MgSO4 and Mg(NO3)2 were selected as draw solution (DS) to dewater synthetic non
      hydrolysed urine. In this process, the Mg2+ reverse salt flux (RSF) were used to
      recover P as struvite. Simultaneously, the urea was recovered in the DS as it is
      poorly rejected by the FO membrane. The results showed that, after concentrating
      the urine by 60%, about 40% of the P and 50% of the N were recovered. XRD and SEM
      - EDX analysis confirmed that P was precipitated as mineral struvite. If
      successfully tested on real urine, this process could be applied to treat the
      urine collected in urban areas e.g., high-rise building. After the filtration,
      the solid struvite could be sold for inland applications whereas the diluted
      fertiliser used for direct fertigation of green walls, parks or for urban
      farming. Finally, reduction in the load of N, P to the downstream wastewater
      treatment plant would also ensure a more sustainable urban water cycle.

PMID- 29635158
TI  - Effects of triclosan in breast milk on the infant fecal microbiome.
AB  - Triclosan is frequently used for its antimicrobial properties and has been
      detected in human serum, urine, and breast milk. Animal and molecular studies
      have shown that triclosan exerts a wide range of adverse health effects at both
      high (ppm) and low (ppb) concentrations. Since triclosan is of growing concern to
      human and environmental health, there is a need to improve extraction procedures
      and to study additional effects from triclosan exposure. In this study, we have
      improved triclosan extraction from breast milk by using salt (MgSO4) to reduce
      emulsion formation and increase water polarity and water (~80%) to enhance the
      overall extraction efficiency (~3.5 fold). This extraction method was applied to
      breast milk samples collected from donors who i) recorded their use of triclosan
      containing personal care products and ii) provided matching infant stool samples.
      Of the participants who had detectable amounts of triclosan in their breast milk,
      nine (75%) of them reported daily use of triclosan-containing personal care
      products. Levels of triclosan in breast milk were compared to the donor's
      infant's fecal microbiome. We found that the bacterial diversity in the fecal
      microbiome of the infants exposed to breast milk with detectable triclosan levels
      differed compared to their peers exposed to milk containing non-detectable
      amounts. This finding implies that exogenous chemicals are impacting microbiome
      diversity.

PMID- 29635161
TI  - Phase of beta-frequency tACS over primary motor cortex modulates corticospinal
      excitability.
AB  - The assessment of corticospinal excitability by means of transcranial magnetic
      stimulation-induced motor evoked potentials is an established diagnostic tool in
      neurophysiology and a widely used procedure in fundamental brain research.
      However, concern about low reliability of these measures has grown recently. One
      possible cause of high variability of MEPs under identical acquisition conditions
      could be the influence of oscillatory neuronal activity on corticospinal
      excitability. Based on research showing that transcranial alternating current
      stimulation can entrain neuronal oscillations we here test whether alpha or beta
      frequency tACS can influence corticospinal excitability in a phase-dependent
      manner. We applied tACS at individually calibrated alpha- and beta-band
      oscillation frequencies, or we applied sham tACS. Simultaneous single TMS pulses
      time locked to eight equidistant phases of the ongoing tACS signal evoked MEPs.
      To evaluate offline effects of stimulation frequency, MEP amplitudes were
      measured before and after tACS. To evaluate whether tACS influences MEP
      amplitude, we fitted one-cycle sinusoids to the average MEPs elicited at the
      different phase conditions of each tACS frequency. We found no frequency-specific
      offline effects of tACS. However, beta-frequency tACS modulation of MEPs was
      phase-dependent. Post hoc analyses suggested that this effect was specific to
      participants with low (<19 Hz) intrinsic beta frequency. In conclusion, by
      showing that beta tACS influences MEP amplitude in a phase-dependent manner, our
      results support a potential role attributed to neuronal oscillations in
      regulating corticospinal excitability. Moreover, our findings may be useful for
      the development of TMS protocols that improve the reliability of MEPs as a
      meaningful tool for research applications or for clinical monitoring and
      diagnosis.

PMID- 29635162
TI  - Variations in response control within at-risk gamblers and non-gambling controls
      explained by GABAergic inhibition in the motor cortex.
AB  - Paired-pulse Transcranial Magnetic Stimulation (TMS) is used to study inhibitory
      and excitatory mechanisms in the motor cortex through the measurement of short
      interval intracortical inhibition (SICI), indicative of GABAergic activity, and
      intracortical facilitation (ICF), indicative of glutamatergic activity. In the
      present study, TMS was delivered to the left motor cortex of 40 participants
      while we measured SICI and ICF at rest. We were interested in whether variation
      between individuals in these modulatory mechanisms is related to inhibitory
      control over responding measured as stop signal reaction time (SSRT). Within the
      same group of participants, we investigated whether SICI, ICF, SSRT, and self
      reported impulsivity, are impaired in participants identified as At-Risk gamblers
      (n = 20) compared to non-gambling controls (n = 20). We found a significant
      negative correlation between SICI strength and SSRT, but no correlation between
      ICF strength and SSRT after controlling for the correlation between SICI and
      SSRT. Thus, poor inhibitory control of responding was associated with weak
      GABAergic activity. When taking into account the effects of substance/alcohol use
      and attention-deficit hyperactivity disorder (ADHD) symptom severity, At-Risk
      gamblers showed elevated self-reported impulsivity, but did not differ from
      controls on SSRT or SICI/ICF. Our study is the first to show that individual
      differences in motor cortex inhibition can predict stopping performance, and the
      first to investigate paired-pulse TMS parameters (together with other impulse
      control measures) in a gambling population.

PMID- 29635163
TI  - Bispecific antibodies in haematological malignancies.
AB  - Bispecific antibodies (bsAbs) combine the binding sites of two monoclonal
      antibodies in one molecule. The close proximity of a tumor specific antigen and
      an effector cell antigen results in a targeted activation of effector cells. The
      mechanism is similar to the chimeric antigen receptor (CAR) T-cells, recently
      approved in two haematologic cancers. CAR T-cells and bsAb represent the most
      powerful tools for major-histocompatibility complex (MHC) independent T-cell
      immune response against cancer. In contrast to CAR T-cells, bsAbs are "off the
      shelf" drugs. As a drawback, the efficacy is dependent on a prolonged
      application. More than 40 years of intensive research generate a plethora of
      bispecific constructs with a remarkable difference in manufacturability,
      stability, half-life time and receptor affinity. Blinatumomab was the first
      approved bsAb in relapsed and refractory acute lymphoblastic leukemia. By the
      mature experience of blinatumomab in more than 10 clinical trials over more than
      one decade, we learned some lessons on how to use this new principle. The
      efficacy is higher in patients with less tumor burden, suggesting the use as
      consolidation more than for initial debulking. Main resistance mechanisms are
      extramedullary relapses and the expression of the inhibitory PD-L1 molecule,
      suggesting the value of combination with checkpoint inhibitors. CD19 loss is
      infrequent after blinatumomab, preserving the option for alternative CD19-direct
      treatments. New bsAbs in lymphoma, myeloma and acute myeloid leukemia enter phase
      I trials, together with many new constructs in solid cancer.

PMID- 29635164
TI  - Reactor staging influences microbial community composition and diversity of
      denitrifying MBBRs- Implications on pharmaceutical removal.
AB  - The subdivision of biofilm reactor in two or more stages (i.e., reactor staging)
      represents an option for process optimisation of biological treatment. In our
      previous work, we showed that the gradient of influent organic substrate
      availability (induced by the staging) can influence the microbial activity (i.e.,
      denitrification and pharmaceutical biotransformation kinetics) of a denitrifying
      three-stage Moving Bed Biofilm Reactor (MBBR) system. However, it is unclear
      whether staging and thus the long-term exposure to varying organic carbon type
      and loading influences the microbial community structure and diversity. In this
      study, we investigated biofilm structure and diversity in the three-stage MBBR
      system (S) compared to a single-stage configuration (U) and their relationship
      with microbial functions. Results from 16S rRNA amplicon libraries revealed a
      significantly higher microbial richness in the staged MBBR (at 99% sequence
      similarity) compared to single-stage MBBR. A more even and diverse microbial
      community was selected in the last stage of S (S3), likely due to exposure to
      carbon limitation during continuous-flow operation. A core of OTUs was shared in
      both systems, consisting of Burkholderiales, Xanthomonadales, Flavobacteriales
      and Sphingobacteriales, while MBBR staging selected for specific taxa (i.e.,
      Candidate division WS6 and Deinococcales). Results from quantitative PCR (qPCR)
      showed that S3 exhibited the lowest abundance of 16S rRNA but the highest
      abundance of atypical nosZ, suggesting a selection of microbes with more diverse
      N-metabolism (i.e., incomplete denitrifiers) in the stage exposed to the lowest
      carbon availability. A positive correlation (p < 0.05) was observed between
      removal rate constants of several pharmaceuticals with abundance of relevant
      denitrifying genes, but not with biodiversity. Despite the previously suggested
      positive relationship between microbial diversity and functionality in macrobial
      and microbial ecosystems, this was not observed in the current study, indicating
      a need to further investigate structure-function relationships for denitrifying
      systems.

PMID- 29635165
TI  - Discovery of 6-chloro-2-(propylthio)-8,9-dihydro-7H-purines containing a
      carboxamide moiety as potential selective anti-lung cancer agents.
AB  - A new series of 6-chloro-2-(propylthio)-8,9-dihydro-7H-purine-8-caboxamide
      derivatives were designed, synthesized, and further evaluated for their
      antiproliferative activities on four human cancer cell lines (A549, MGC803, PC-3
      and TE-1). The structure-activity relationships (SARs) studies were conducted
      through the variation in the two regions, which including position 8 and 9, of
      purine core. One of the compounds, 8, containing a terminal piperazine appendage
      with a carboxamide moiety at position 8 and phenyl group at position 9 of 6
      chloro-8,9-dihydro-7H-purine core, showed the most potent antiproliferative
      activity and good selectivity between cancer and normal cells (IC50 values of
      2.80 MUM against A549 and 303.03 MUM against GES-1, respectively). In addition,
      compound 8 could inhibit the colony formation and migration of A549 cells in a
      concentration-dependent manner, as well as induce the apoptosis possibly through
      the intrinsic pathway.

PMID- 29635176
TI  - Mechanism and kinetics of photochemical transformation of ketoprofen and its
      degradation intermediates.
AB  - Ketoprofen, 2-(3-benzoylphenyl)-propionic acid, a widely used non-steroidal anti
      inflammatory drug, is considered as an important water pollutant. Kinetics and
      mechanism of its photolytic transformation in aqueous solutions was studied
      experimentally and partial reaction steps were modelled by means of quantum
      chemistry methods. While the rate of ketoprofen photolysis was not significantly
      affected by its acid-base equilibrium, a marked influence of pH on the subsequent
      degradation reactions was observed. At pH 1.3, two oxygenated primary products
      were identified, that underwent fast photolysis. Deprotonated form of ketoprofen
      was transformed preferentially to ethylbenzophenone and further degradation
      proceeded substantially slower. Oxygen participated on photolytic processes both
      as a reactant and the triplet state quencher. The active involvement of water
      molecules in the reaction mechanism was investigated by comparative experiments
      in acetonitrile. The phototransformation mechanism proposed based on the
      experimental data corresponded well with the theoretical results.

PMID- 29635171
TI  - Effects of dietary Allium hookeri root on growth performance and antioxidant
      activity in young broiler chickens.
AB  - The objective of this experiment was to evaluate the antioxidant potential of
      Allium hookeri (AH) root in two forms, powdered AH root and fermented powdered AH
      root, to demonstrate its value as an antibiotic alternative feed additive for
      broiler chickens. A total of 125 male Ross-708 broiler chickens were randomly
      assigned to five groups (n = 25 birds/group) and fed standard diets supplemented
      with root or fermented root of AH at two different levels (1% or 5%). Control
      birds were provided with non-supplemented basal diets. Body weights was measured
      at days 14 and 21 of age. To monitor antioxidant activities, heme oxygenase
      (HMOX), aflatoxin B1 aldehyde reductase (AFAR), superoxide dismutase 1 (SOD1),
      and catalase (CAT) enzyme levels were quantified by real-time PCR in the jejunums
      21-day-old birds. Also, serum levels of SOD, CAT, and malondialdehyde (MDA) were
      measured using commercial kits. The results showed greater body weight gains at
      day 14 in chickens fed diets supplemented with 1% AH root, as compared to the
      control group (p < 0.05). Up-regulated transcript levels of AFAR, HMOX1, and CAT
      were observed in the jejunum of chickens fed diets supplemented with AH. The
      serum levels SOD and CAT were significantly increased (p < 0.05) in groups
      treated with AH, whereas MDA levels were decreased in groups fed diets
      supplemented with AH, as compared to the control group. These results indicated
      that an optimum level of dietary AH supplementation to young broiler chickens
      influences growth and improves antioxidant activities.

PMID- 29635180
TI  - Plasma impact on structural, morphological and optical properties of copper
      acetylacetonate thin films.
AB  - The influence of plasma exposure on structural, morphological and optical
      properties of copper (II) acetylacetonate thin films deposited by thermal
      evaporation technique was investigated. Copper (II) acetylacetonate as-grown thin
      films were exposed to the atmospheric plasma for different times. The exposure of
      as-grown cu(acac)2 thin film to atmospheric plasma for 5min modified its
      structural, morphological and optical properties. The effect of plasma exposure
      on structure and roughness of cu(acac)2 thin films was evaluated by XRD and AFM
      techniques, respectively. The XRD results showed an increment in crystallinity
      due to exposure for 5min, but, when the exposure time reaches 10min, the film was
      transformed to an amorphous state. The AFM results revealed a strong modification
      of films roughness when the average roughness decreased from 63.35nm to ~1nm as a
      result of interaction with plasma. The optical properties of as-grown and plasma
      exposured cu(acac)2 thin films were studied using spectrophotometric method. The
      exposure of cu(acac)2 thin films to plasma produced the indirect energy gap
      decrease from 3.20eV to 2.67eV for 10min exposure time. The dispersion parameters
      were evaluated in terms of single oscillator model for as-grown and plasma
      exposured thin films. The influence of plasma exposure on third order optical
      susceptibility was studied.

PMID- 29635175
TI  - The quantitative studies on gas explosion suppression by an inert rock dust
      deposit.
AB  - The traditional defence against propagating gas explosions is the application of
      dry rock dust, but not much quantitative study on explosion suppression of rock
      dust has been made. Based on the theories of fluid dynamics and combustion, a
      simulated study on the propagation of premixed gas explosion suppressed by
      deposited inert rock dust layer is carried out. The characteristics of the
      explosion field (overpressure, temperature, flame speed and combustion rate) at
      different deposited rock dust amounts are investigated. The flame in the pipeline
      cannot be extinguished when the deposited rock dust amount is less than 12 kg/m3.
      The effects of suppressing gas explosion become weak when the deposited rock dust
      amount is greater than 45 kg/m3. The overpressure decreases with the increase of
      the deposited rock dust amounts in the range of 18-36 kg/m3 and the flame speed
      and the flame length show the same trends. When the deposited rock dust amount is
      36 kg/m3, the overpressure can be reduced by 40%, the peak flame speed by 50%,
      and the flame length by 42% respectively, compared with those of the gas
      explosion of stoichiometric mixture. In this model, the effective raised dust
      concentrations to suppress explosion are 2.5-3.5 kg/m3.

PMID- 29635172
TI  - Combination of human acetylcholinesterase and serum albumin sensing surfaces as
      highly informative analytical tool for inhibitor screening.
AB  - In the continuous research for potential drug lead candidates, the availability
      of highly informative screening methodologies may constitute a decisive element
      in the selection of best-in-class compounds. In the present study, a surface
      plasmon resonance (SPR)-based assay was developed and employed to investigate
      interactions between human recombinant AChE (hAChE) and four known ligands:
      galantamine, tacrine, donepezil and edrophonium. To this aim, a sensor chip was
      functionalized with hAChE using mild immobilization conditions to best preserve
      enzyme integrity. Binding affinities and, for the first time, kinetic rate
      constants for all drug-hAChE complexes formation/disruption were determined.
      Inhibitors were classified in two groups: slow-reversible and fast-reversible
      binders according to respective target residence time. Combining data obtained on
      drug-target residence time with data obtained on serum albumin binding levels, a
      good correlation with potency, plasma protein binding in vivo, and administration
      regimen was found. The outcomes of this work demonstrated that the developed SPR
      based assay is suitable for the screening, the binding affinity ranking and the
      kinetic evaluation of hAChE inhibitors. The method proposed ensures a simpler and
      cost-effective assay to quantify kinetic rate constants for inhibitor-hAChE
      interaction as compared with other proposed and published methods. Eventually,
      the determination of residence time in combination with preliminary ADME studies
      might constitute a better tool to predict in vivo behaviour, a key information
      for the research of new potential drug candidates.

PMID- 29635166
TI  - Targeting the entrance channel of NNIBP: Discovery of diarylnicotinamide 1,4
      disubstituted 1,2,3-triazoles as novel HIV-1 NNRTIs with high potency against
      wild-type and E138K mutant virus.
AB  - Inspired by our previous efforts on the modifications of diarylpyrimidines as HIV
      1 non-nucleoside reverse transcriptase inhibitors (NNRTI) and reported
      crystallography study, novel diarylnicotinamide derivatives were designed with a
      "triazole tail" occupying the entrance channel in the NNRTI binding pocket of the
      reverse transcriptase to afford additional interactions. The newly designed
      compounds were then synthesized and evaluated for their anti-HIV activities in MT
      4 cells. All the compounds showed excellent to good activity against wild-type
      HIV-1 strain with EC50 of 0.02-1.77 MUM. Evaluations of selected compounds
      against more drug-resistant strains showed these compounds had advantage of
      inhibiting E138K mutant virus which is a key drug-resistant mutant to the new
      generation of NNRTIs. Among this series, propionitrile (3b2, EC50(IIIB) = 0.020
      MUM, EC50(E138K) = 0.015 MUM, CC50 = 40.15 MUM), pyrrolidin-1-ylmethanone (3b8,
      EC50(IIIB) = 0.020 MUM, EC50(E138K) = 0.014 MUM, CC50 = 58.09 MUM) and
      morpholinomethanone (3b9, EC50(IIIB) = 0.020 MUM, EC50(E138K) = 0.027 MUM, CC50 =
      180.90 MUM) derivatives are the three most promising compounds which are equally
      potent to the marketed drug Etravirine against E138K mutant strain but with much
      lower cytotoxicity. Furthermore, detailed SAR, inhibitory activity against RT and
      docking study of the representative compounds are also discussed.

PMID- 29635170
TI  - Resilience in high-risk adolescents of mothers with recurrent depressive
      disorder: The contribution of fathers.
AB  - This study examines the role of paternal emotional support as a resilience
      promoter in offspring of mothers with depression by considering the role of
      fathers' mental health and the quality of the couple relationship. Two hundred
      and sixty-five mothers with recurrent unipolar depression, partners and
      adolescents from Wales were assessed. Paternal emotional support, couple
      relationship quality, and paternal depression were assessed at baseline;
      adolescent mental health symptoms were assessed using the Child and Adolescent
      Psychiatric Assessment at follow-up. Results showed evidence of an indirect
      pathway whereby couple relationship quality predicted paternal emotional support
      (beta = -.21, 95% CI [-.34, -.08]; p = .002) which in turn predicted adolescent
      depression (beta = -.18, 95% CI [-.33, -.04]; p = .02), but not disruptive
      behaviours (beta = -.08, 95% CI [-.22, .07]; p = .30), after controlling for
      relevant confounders. The findings highlight that fathers and the broader family
      system play an important role in enhancing resilience to depression symptoms in
      at-risk adolescents.

PMID- 29635178
TI  - The synthesis of super-small nano hydroxyapatite and its high adsorptions to
      mixed heavy metallic ions.
AB  - A "molecular cage" was possibly built in glucose alkaline solution to limit the
      chemical reaction in a tiny space to control the size and morphology of HA
      nanoparticles. A possible reaction mechanism of HA nanoparticles confined space
      synthesis was proposed in this work. The super-small HA nanoparticles were
      successfully obtained in the first time in mild and green condition which had a 7
      nm diameter. The adsorptions to Pb2+, Zn2+, Ni2+, Cd2+ ions in their mixture
      solution by the synthesized HA nanoparticles were studied. The adsorbent showed
      huge adsorption capacities for the targets (Pb2+ = 3289 mg/g, Zn2+ = 3150 mg/g,
      Ni2+ = 3061 mg/g and Cd2+ = 2784 mg/g), which indicated an excellent performance
      of the synthesized nano material in water treatment. Freundlich equation analysis
      and SEM images of the adsorption products suggested multilayer adsorptions to the
      targets, and a new recrystalline type adsorption on the surface of the host was
      found. Some Ca atoms in HA nanoparticles were also found to be substituted by the
      heavy metallic elements in the initial stage of the adsorptions. The synthesized
      nano material exhibits better application prospect in wastewater treatment field
      for its easy synthesis, low-cost and environmental friendly properties.

PMID- 29635183
TI  - Effect of microwave treatment on structure of binders based on sodium
      carboxymethyl starch: FT-IR, FT-Raman and XRD investigations.
AB  - The paper deals with the influence of the microwave treatment on sodium
      carboxymethyl starch (CMS-Na) applied as a binder for moulding sands. The Fourier
      transformation infrared spectrometry (FT-IR), Raman spectroscopy (FT-Raman) and
      XRD analysis data of native potato starch and three different carboxymethyl
      starches (CMS-Na) with various degree of substitution (DS) before and after
      exposition to microwave radiation have been compared. FT-IR studies showed that
      polar groups present in CMS-Na structure take part in the formation of new
      hydrogen bonds network after water evaporation. However, these changes depend on
      DS value of the modified starch. The FT-Raman study confirmed that due to the
      impact on the samples by microwave, the changes of intensity in the
      characteristic bands associated with the crystalline regions in the sample were
      noticed. The X-ray diffraction data for microwave treated CMS-Na samples have
      been compared with the diffractograms of initial materials and analysis of XRD
      patterns confirmed that microwave-treated samples exhibit completely amorphous
      structure. Analysis of structural changes allows to state that the binding of
      sand grains in moulding sand with CMS-Na polymeric binder consists in the
      formation of hydrogen bonds networks (physical cross-linking).

PMID- 29635181
TI  - Investigations on Mg-borate kinetics and mechanisms during evaporation, dilution
      and crystallization by Raman spectroscopy.
AB  - Raman spectra of boron-concentrated, diluted, and corresponding mother solutions
      of brine were recorded at 298.15 K. The main polyborate anions present and their
      interactions in brine during evaporation and dilution were proposed according to
      the Raman spectra. The polyborate anions B(OH)3, B3O3(OH)4-, B5O6(OH)4-, and
      B6O7(OH)62- were found to be the main forms in boron-concentrated brine with
      B3O3(OH)4- ion being the principal form. Diluting brines with water accelerated
      depolymerization of B5O6(OH)4- and B6O7(OH)62- anions into B(OH)3 and B3O3(OH)4-
      ions and generated OH- ions, causing the pH of the solutions to increase from 4.2
      to almost 8.0. Mg-borates precipitated from all diluted solutions could be
      classified as either hexaborates or triborates. A mechanism of solid phase
      transformation was also proposed and discussed based on Raman spectra analysis
      and solid species and solution pH data.

PMID- 29635167
TI  - Novel sarsasapogenin-triazolyl hybrids as potential anti-Alzheimer's agents:
      Design, synthesis and biological evaluation.
AB  - Sarsasapogenin, an active ingredient in Rhizoma anemarrhenae, is a promising
      bioactive lead compound in the treatment of Alzheimer's disease. To search for
      more efficient anti-Alzheimer agents, a series of novel sarsasapogenin-triazolyl
      hybrids were designed, synthesized, and evaluated for their Abeta1-42 aggregation
      inhibitory activities. Most of these new hybrids displayed potent Abeta1-42
      aggregation inhibition. In particular, the promising compounds 6j and 6o
      displayed a better ability to interrupt the formation of Abeta1-42 fibrils than
      curcumin. Moreover, 6j and 6o exhibited moderate neuroprotective effects against
      H2O2-induced neurotoxicity in SH-SY5Y cells. To investigate whether 6j and 6o
      could improve cognitive deficits, we performed behavioral tests to examine the
      learning and memory impairments induced by intracerebroventricular injection of
      Abeta1-42 (ICV-Abeta1-42) in mice and TUNEL staining to observe neuronal
      apoptosis in the hippocampus. The results obtained indicated that oral treatment
      with 6j and 6o significantly ameliorated cognitive impairments in behavioral
      tests and TUNEL staining showed that 6j and 6o attenuated neuronal loss in the
      brain. Taken together, the results we obtained showed that the sarsasapogenin
      skeleton could be a promising structural template for the development of new anti
      Alzheimer drug candidates, and compounds 6j and 6o have the potential to be
      important lead compounds for further research.

PMID- 29635182
TI  - Self-aggregation of bio-surfactants within ionic liquid 1-ethyl-3
      methylimidazolium bromide: A comparative study and potential application in
      antidepressants drug aggregation.
AB  - Aggregation behavior of bio-surfactants (BS) sodium cholate (NaC) and sodium
      deoxycholate (NaDC) within aqueous solution of ionic liquid (IL) 1-ethyl-3
      methylimidazolium bromide [Emim][Br] has been investigated using surface tension,
      conductivity, steady state fluorescence, FT-IR and dynamic light scattering (DLS)
      techniques. Various interfacial and thermodynamic parameters are determined in
      the presence of different wt% of IL [Emim][Br]. Information regarding the local
      microenvironment and size of the aggregates is obtained from fluorescence and
      DLS, respectively. FT-IR spectral response is used to reveal the interactions
      taking place within aqueous NaC/NaDC micellar solutions. It is noteworthy to
      mention that increasing wt% of [Emim][Br] results in an increase in the
      spontaneity of micelle formation and the hydrophilic IL shows more affinity for
      NaC as compared to NaDC. Further, the micellar solutions of BS-[Emim][Br] are
      utilized for studying the aggregation of antidepressants drug promazine
      hydrochloride (pH). UV-vis spectroscopic investigation reveals interesting
      outcomes and the results show changes in spectral absorbance of PH drug on the
      addition of micellar solution (BS-[Emim][Br]). Highest binding affinity and most
      promising activity are shown for NaC as compared to NaDC.

PMID- 29635177
TI  - Novel mesoporous TiO2@g-C3N4 hollow core@shell heterojunction with enhanced
      photocatalytic activity for water treatment and H2 production under simulated
      sunlight.
AB  - A novel mesoporous TiO2@g-C3N4 hollow core@shell heterojunction photocatalyst was
      engineered for the first time by in situ calcining and growing of cyanamide (CY)
      on the surface of TiO2. The HTCN-1 possesses good structure and performance when
      the addition amount of CY is 1 mL. HTCN-1 shows high photocatalytic activity
      toward congo red (CR), rhodamine B (RhB), phenol and ciprofloxacin (CIP) with
      degradation efficiencies of 97%, 100%, 73%, and 74%, respectively. HTCN-1 also
      displays high photocatalytic activity for H2 generation at rate of 7.9 MUmol h-1.
      A possible charger transfer mechanism and photocatalytic degradation mechanism of
      HTCN-1 are proposed basing on the experiment results. The enhanced photocatalytic
      activity may be attributed to the higher charge transfer efficiency of
      photogenerated electron-hole (e--h+) pairs caused by close contacts, a larger
      interfacial area, and the higher barrier for conduction bending. What's more,
      HTCN-1 possesses relatively high stability during the entire photoreaction
      process. Given the unique spatial structure and superior photocatalytic
      characteristics of the HTCN-1, there is great potential for applications in water
      treatment and H2 generation.

PMID- 29635169
TI  - Antiproliferative hydrogen sulfide releasing evodiamine derivatives and their
      apoptosis inducing properties.
AB  - To explore antitumor agents with high efficiency and selectivity, two series of
      16 H2S donating evodiamine derivatives 8-12 were synthesized and characterized by
      1H NMR, 13C NMR and HRMS. Their antiproliferative activities were tested against
      five cancer cell lines (Bel-7402, MCF-7, SGC-7901, Caco-2 and HL-60) and human
      normal peripheral blood mononuclear cells. Among them, compound 12c showed the
      most potent inhibitory activities against human leukemia HL-60 and epithelial
      colorectal adenocarcinoma Caco-2 cells with IC50 values of 0.58 and 2.02 MUM,
      respectively. Additionally, high selectivity was also observed between human
      normal peripheral blood mononuclear cells and human leukemia HL-60 cells. Further
      mechanism studies confirmed that 12c could induce apoptosis, arrest cell cycle at
      the G2/M phase and lead to mitochondrial dysfunction in HL-60 cells. Furthermore,
      western blot assay demonstrated that 12c induced the intrinsic apoptotic
      mitochondrial pathway by upregulating protein expression of Bax, cytochrome c,
      caspase-3, -9 and p53, and downregulating the relative levels of Bcl-2. The
      levels of cell cycle related proteins cyclin B1 and cdc2 were also downregulated
      in which G2/M phase arrest was confirmed. Overall, 12c possessed immense
      potential for the discovery of antitumor candidates with high efficiency and
      selectivity.

PMID- 29635174
TI  - Multiple measures of HPA axis function in ultra high risk and first-episode
      schizophrenia patients.
AB  - INTRODUCTION: Abnormalities within hypothalamus-pituitary-adrenal (HPA) axis
      might interact with other neurobiological systems to enhance the risk of
      psychosis. Most of the neurodevelopmental and HPA axis changes occur in
      adolescence; this is also the period when prodromal and psychotic symptoms occur
      for the first time. More knowledge about how various stress components interact
      can advance understanding of the link between psychosis and the HPA axis. METHOD:
      We examined 41 ultra high-risk (UHR) patients and 40 antipsychotic-naive first
      episode schizophrenia (FES) patients and compared them with 47 matched controls.
      The Perceived Stress Scale and the Recent Life Events Questionnaire were used to
      assess the stress levels. Day-time saliva samples were taken to measure cortisol.
      The pituitary gland volume was measured manually on the structural MRI using
      stereology. RESULTS: Only the UHR patients, had a higher cortisol increase just
      after awakening (p = 0.009) compared to healthy controls. In UHR patients, we
      found a negative correlation between cortisol increase after awakening and
      symptom severity (p = 0.008). Pituitary gland volume and diurnal cortisol were
      not significantly different among the three groups. There was no correlation
      between pituitary gland volume, perceived stress/recent life events and any of
      the cortisol measures or symptoms. CONCLUSION: Symptom severity during the very
      early phase of illness (UHR) seems to be associated with altered cortisol
      increase. Longitudinal studies in UHR patients would be useful to examine how
      stress levels affect the course of the illness.

PMID- 29635173
TI  - Proteomic plasma profile of psoriatic patients.
AB  - BACKGROUND: Psoriasis is a chronic, immune-mediated inflammatory skin disease
      with severe consequences for the whole organism. The lack of complete knowledge
      of the main factors predisposing an individual to the appearance of psoriatic
      lesions, has recently led to the search for modifications in biochemical pathways
      participating in the development of this disease. We therefore aimed to
      investigate changes in the plasma proteomic profile of patients with psoriasis.
      MATERIAL AND METHODS: A proteomics approach was used to analyze the expression of
      proteins in plasma from psoriatic patients and healthy controls (sex- and age
      matched individuals). The analysis was performed using gel electrophoresis,
      followed by nanoflow LC-MS/MS using a Q-Exactive OrbiTrap mass spectrometer.
      RESULTS: Proteomic data indicated a significant decrease in the level of proteins
      involved in lipid metabolism, such as apolipoprotein M, and proteins involved in
      the management of vitamin D levels in psoriatic patients' plasma. These changes
      were accompanied by the expression of proteins involved in immune response and
      signal transduction. This was particularly evident by the level of
      transcriptional factors, including AT motif binding factor 1, which regulates
      excessive cellular proliferation and differentiation. It was also suggested that
      psoriasis development was associated with increased expression of proteins
      directly involved in signaling molecule secretion [biotinidase and BAI1
      associated protein 3]. In addition, the lipid peroxidation product - 4
      hydroxynonenal (4-HNE) generates higher level of adducts with proteins in the
      plasma of psoriatic patients. Moreover, plasma proteins from healthy subjects
      creating with 4-HNE adducts were mainly characterized as structural, while in the
      plasma of psoriatic patients, increased levels of 4-HNE-protein adducts with
      catalytic activity were observed. CONCLUSION: The results presented herein
      confirm the current knowledge about the profile of proteins responsible for the
      immune response and management of vitamin D in the plasma of psoriatic patients.
      However, several new proteins were also identified, which are involved in signal
      transduction and lipid metabolism as well as catalytic activity. The expression
      or structure of these proteins was shown to change through the course of the
      development of psoriasis. This knowledge may help contribute to the design of
      more specific pharmacotherapy.

PMID- 29635179
TI  - Geometry-dependent DNA-TiO2 immobilization mechanism: A spectroscopic approach.
AB  - DNA nucleotides are used as a molecular recognition system on electrodes modified
      to be applied in the detection of various diseases, but immobilization
      mechanisms, as well as, charge transfers are not satisfactorily described in the
      literature. An electrochemical and spectroscopic study was carried out to
      characterize the molecular groups involved in the direct immobilization of DNA
      structures on the surface of nanostructured TiO2 with the aim of evaluating the
      influence of the geometrical aspects. X-ray photoelectron spectroscopy at O1s and
      P2p core levels indicate that immobilization of DNA samples occurs through
      covalent (POTi) bonds. X-ray absorption spectra at the Ti2p edge reinforce this
      conclusion. A new species at 138.5eV was reported from P2p XPS spectra analysis
      which plays an important role in DNA-TiO2 immobilization. The POTi/OTi ratio
      showed that quantitatively the DNA immobilization mechanism is dependent on their
      geometry, becoming more efficient for plasmid ds-DNA structures than for PCR ds
      DNA structures. The analysis of photoabsorption spectra at C1s edge revealed that
      the molecular groups that participate in the C1s->LUMO electronic transitions
      have different pathways in the charge transfer processes at the DNA-TiO2
      interface. Our results may contribute to additional studies of immobilization
      mechanisms understanding the influence of the geometry of different DNA molecules
      on nanostructured semiconductor and possible impact to the charge transfer
      processes with application in biosensors or aptamers.

PMID- 29635168
TI  - 2-Benzylpiperazine: A new scaffold for potent human carbonic anhydrase
      inhibitors. Synthesis, enzyme inhibition, enantioselectivity, computational and
      crystallographic studies and in vivo activity for a new class of intraocular
      pressure lowering agents.
AB  - Two series of 2-benzylpiperazines have been prepared and tested for the
      inhibition of physiologically relevant isoforms of human carbonic anhydrases
      (hCA, EC 4.2.1.1). The new compounds carry on one nitrogen atom of the piperazine
      ring a sulfamoylbenzamide group as zinc-binding moiety, and different
      alkyl/acyl/sulfonyl groups on the other nitrogen. Regio- and stero-isomers are
      described. The majority of these compounds showed Ki values in the low-medium
      nanomolar range against hCA I, II and IV, but not IX. In many instances
      interaction with the enzyme was enantioselective. The binding mode has been
      studied by means of X-ray crystallography and molecular modelling. Two compounds,
      evaluated in rabbit models of glaucoma, were able to significantly reduce
      intraocular pressure, making them interesting candidates for further studies.

PMID- 29635184
TI  - Diketo modification of curcumin affects its interaction with human serum albumin.
AB  - Curcumin isoxazole (CI) and Curcumin pyrazole (CP), the diketo modified
      derivatives of Curcumin (CU) are metabolically more stable and are being explored
      for pharmacological properties. One of the requirements in such activities is
      their interaction with circulatory proteins like human serum albumin (HSA). To
      understand this, the interactions of CI and CP with HSA have been investigated
      employing absorption and fluorescence spectroscopy and the results are compared
      with that of CU. The respective binding constants of CP, CI and CU with HSA were
      estimated to be 9.3*105, 8.4*105 and 2.5*105M-1, which decreased with increasing
      salt concentration in the medium. The extent of decrease in the binding constant
      was the highest in CP followed by CI and CU. This revealed that along with
      hydrophobic interaction other binding modes like electrostatic interactions
      operate between CP/CI/CU with HSA. Fluorescence quenching studies of HSA with
      these compounds suggested that both static and dynamic quenching mechanisms
      operate, where the contribution of static quenching is higher for CP and CI than
      that for CU. From fluorescence resonance energy transfer studies, the binding
      site of CU, CI and CP was found to be in domain IIA of HSA. CU was found to bind
      in closer proximity with Trp214 as compared to CI and CP and the same was
      responsible for efficient energy transfer and the same was also established by
      fluorescence anisotropy measurements. Furthermore docking simulation complemented
      the experimental observation, where both electrostatic as well as hydrophobic
      interactions were indicated between HSA and CP, CI and CU. This study is useful
      in designing more stable CU derivatives having suitable binding properties with
      proteins like HSA.

PMID- 29635186
TI  - Ultrafine particle libraries for exploring mechanisms of PM2.5-induced toxicity
      in human cells.
AB  - Air pollution worldwide, especially in China and India, has caused serious health
      issues. Because PM2.5 particles consist of solid particles of diverse properties
      with payloads of inorganic, organic and biological pollutants, it is still not
      known what the major toxic components are and how these components induce
      toxicities. To explore this complex issue, we apply reductionism principle and an
      ultrafine particle library approach in this work. From investigation of 63
      diversely functionalized ultrafine particles (FUPs) with adsorbed key pollutants,
      our findings indicate that 1) only certain pollutants in the payloads of PM2.5
      are responsible for causing cellular oxidative stress, cell apoptosis, and
      cytotoxicity while the particle carriers are much less toxic; 2) pollutant
      induced cellular oxidative stress and oxidative stress-triggered apoptosis are
      identified as one of the dominant mechanisms for PM2.5-induced cytotoxicity; 3)
      each specific toxic component on PM2.5 (such as As, Pb, Cr or BaP) mainly affects
      its specific target organ(s) and, adding together, these pollutants may cause
      synergistic or just additive effects. Our findings demonstrate that reductionism
      concept and model PM2.5 particle library approach are very effective in our
      endeavor to search for a better understanding of PM2.5-induced health effects.

PMID- 29635187
TI  - Energy security impacts of a severe drought on the future Finnish energy system.
AB  - Finland updated its Energy and Climate Strategy in late 2016 with the aim of
      increasing the share of renewable energy sources, increasing energy self
      sufficiency and reducing greenhouse gas emissions. Concurrently, the issue of
      generation adequacy has grown more topical, especially since the record-high
      demand peak in Finland in January 2016. This paper analyses the Finnish energy
      system in years 2020 and 2030 by using the EnergyPLAN simulation tool to model
      whether different energy policy scenarios result in a plausible generation
      inadequacy. Moreover, as the Nordic energy system is so heavily dependent on
      hydropower production, we model and analyse the impacts of a severe drought on
      the Finnish energy system. We simulate hydropower availability according to the
      weather of the worst drought of the last century (in 1939-1942) with Finnish
      Environment Institute's Watershed Simulation and Forecasting System and we
      analyse the indirect impacts via reduced availability of electricity imports
      based on recent realised dry periods. Moreover, we analyse the environmental
      impacts of hydropower production during the drought and peak demand period and
      the impacts of climate change on generation adequacy in Finland. The results show
      that the scenarios of the new Energy and Climate Strategy result in an improved
      generation adequacy comparing to the current situation. However, a severe drought
      similar to that experienced in 1940s could cause a serious energy security
      threat.

PMID- 29635185
TI  - Acridine-based fluorescence chemosensors for selective sensing of Fe3+ and Ni2+
      ions.
AB  - Two novel acridine-based fluorescence chemosensors (L1 and L2) were prepared and
      their metal ions sensing properties were investigated. L1 (L2) exhibited an
      excellent selective fluorescence response toward Fe3+ (Ni2+) and the
      stoichiometry ratio of L1-Fe3+ and L2-Ni2+ were 1:1. The detection limits of L1
      and L2 were calculated by the fluorescence titration to be 4.13MUM and 1.52MUM,
      respectively, which were below the maximum permissive level of Fe3+ and Ni2+ ions
      in drinking water set by the EPA. The possible mechanism of the fluorescence
      detection of Fe3+ and Ni2+ had been proposed according to the analysis of Job's
      plot, IR spectra and ESI-MS. The determination of Fe3+ and Ni2+ ions in living
      cells had been applied successfully.

PMID- 29635188
TI  - Strategies to reduce mass and photons transfer limitations in heterogeneous
      photocatalytic processes: Hexavalent chromium reduction studies.
AB  - The current work presents different approaches to overcome mass and photon
      transfer limitations in heterogeneous photocatalytic processes applied to the
      reduction of hexavalent chromium to its trivalent form in the presence of a
      sacrificial agent. Two reactor designs were tested, a monolithic tubular
      photoreactor (MTP) and a micro-meso-structured photoreactor (NETmix), both
      presenting a high catalyst surface area per reaction liquid volume. In order to
      reduce photon transfer limitations, the tubular photoreactor was packed with
      transparent cellulose acetate monolithic structures (CAM) coated with the
      catalyst by a dip-coating method. For the NETmix reactor, a thin film of
      photocatalyst was uniformly deposited on the front glass slab (GS) or on the
      network of channels and chambers imprinted in the back stainless steel slab (SSS)
      using a spray system. The reaction rate for the NETmix photoreactor was evaluated
      for two illumination sources, solar light or UVA-LEDs, using the NETmix with the
      front glass slab or/and back stainless steel slab coated with TiO2-P25. The
      reusability of the photocatalytic films on the NETmix walls was also evaluated
      for three consecutive cycles using fresh Cr(VI) solutions. The catalyst
      reactivity in combination with the NETmix-SSS photoreactor is almost 70 times
      superior to one obtained with the MTP.

PMID- 29635193
TI  - Soil microbial biomass: A key soil driver in management of ecosystem functioning.
AB  - Although patterns of microbial diversity and biomass have been described and
      reviewed at local and regional scales, a unifying driver, or set of environmental
      drivers affecting soil microbial biomass (SMB) pattern at global level is still
      missing. Biomass of soil microbial community, known as SMB is considered widely
      as the index of soil fertility and ecosystem productivity. The escalating soil
      stresses due to land degradation and climatic variability are directly correlated
      with loss of microbial diversity and abundance or biomass dynamics. Therefore,
      alleviating soil stresses on microbial communities with ecological restoration
      could reduce the unpredictability and turnover rates of SMB. Thus, the key
      ecological factors which stabilize the SMB and minimize its turnover, are
      supposed to play an important role in the soil nutrient dynamics and productivity
      of the ecosystems. Because of the existing public concern about the deleterious
      impacts of ecosystem degradation, there is an increasing interest in improving
      the understanding of SMB, and the way, it contributes to restoration and
      functioning of ecosystems.

PMID- 29635189
TI  - Simultaneous electricity production and antibiotics removal by microbial fuel
      cells.
AB  - The removal of antibiotics is crucial for improvement of water quality in animal
      wastewater treatment. In this paper, the performance of microbial fuel cell (MFC)
      in terms of degradation of typical antibiotics was investigated. Electricity was
      successfully produced by using sludge supernatant mixtures and synthesized animal
      wastewater as inoculation in MFC. Results demonstrated that the stable voltage,
      the maximum power density and internal resistance of anaerobic self-electrolysis
      (ASE) -112 and ASE-116 without antibiotics addition were 0.574 V, 5.78 W m-3 and
      28.06 Omega, and 0.565 V, 5.82 W m-3 and 29.38 Omega, respectively. Moreover,
      when adding aureomycin, sulfadimidine, roxithromycin and norfloxacin into the
      reactors, the performance of MFC was inhibited (0.51 V-0.41 V), while the output
      voltage was improved with the decreased concentration of antibiotics. However,
      the removal efficiency of ammonia nitrogen (NH3-N) and total phosphorus (TP) were
      both obviously enhanced. Simultaneously, LC-MS analysis showed that the removal
      efficiency of aureomycin, roxithromycin and norfloxacin were all 100% and the
      removal efficiency of sulfadimidine also reached 99.9%. These results indicated
      that antibiotics displayed significantly inhibitions for electricity performance
      but improved the quality of water simultaneously.

PMID- 29635190
TI  - "It can be challenging, it can be scary, it can be gratifying": Obstetricians'
      narratives of negotiating patient choice, clinical experience, and standards of
      care in decision-making.
AB  - This paper examines obstetricians' perceptions of standards of care and patient
      centered care in clinical decision-making in childbirth. Patient-centered care
      and standardization of medicine are two social movements that seek to change how
      physicians make clinical decisions. Sociologists question if these limit
      physician discretion and weaken their social power; the degree to which this
      occurs in everyday practice is up for debate. Of additional concern is how
      physicians deal with observed tensions between these ideals. These questions are
      answered through in-depth interviews with 50 self-selected obstetricians from
      Massachusetts, Louisiana, and Vermont collected between 2013 and 2015. Interview
      data was analyzed using a grounded theory and template approach. The author
      problematizes obstetricians' attitudes about standards of care and shared
      decision-making, mechanisms that encourage or discourage these approaches to
      decision-making, and how obstetricians negotiate tensions between patient choice,
      clinical experience, and standards. The key findings are that most obstetricians
      feel they have the authority to interpret the appropriateness of standards and
      patient choice on a case-by-case basis. They feel empowered and/or constrained by
      pressures to practice patient-centered care and standards depending upon their
      style of practice and the organizational context. Following standards of care is
      encouraged through organizational mechanisms such as pressure from colleagues,
      malpractice threat, hospital policy, and payer restrictions. Practicing shared
      decision-making is challenged when the patient wants something that violates the
      physician's clinical experience and/or standards of care. When obstetricians
      prioritize patient choice over experience and/or standards this is done for moral
      reasons, less so because of organizational pressures. These findings have
      implications for theorizing the social status of medical professionals,
      understanding how physicians deal with tensions between standardized and
      individualized ideals in medicine, and illuminating the way obstetricians
      interpret power in the physician-patient relationship.

PMID- 29635197
TI  - Conversions between natural wetlands and farmland in China: A multiscale
      geospatial analysis.
AB  - Agricultural activity is widely recognized as a leading driver of natural wetland
      loss in many parts of the world. However, little is known about the
      spatiotemporal patterns of conversion between natural wetlands and farmland in
      China. This information deficiency has limited decision-making for the
      sustainable management of natural wetland ecosystems. In this study, we
      explicitly quantified bidirectional natural wetland-farmland conversions during
      the periods of 1990-2000 and 2000-2010 at multiple spatiotemporal scales. Our
      results revealed that about 60% (15,765km2) of China's lost natural wetlands were
      due to agricultural encroachment for grain production, 74.7% (11,778km2) of which
      occurred from 1990 to 2000. Natural wetland conversion to farmland was highest in
      Northeast China (13,467km2 or 85.4%), whereas the natural wetlands in Northwest
      China demand extra attention because of a notable increase of agricultural
      encroachment. Natural wetlands in the humid zone experienced tremendous
      agricultural encroachment, leading to a loss of 10,649km2, accounting for 67.5%
      of the total agriculture-induced natural wetland loss in China. On the other
      hand, a total of 1369km2 of natural wetlands were restored from farmland, with
      66.3% of this restoration occurring between 2000 and 2010, primarily in Northeast
      China and the humid zone. Although a series of national policies and population
      pressure resulted in agricultural encroachment into natural wetlands, there are
      also policies and management measures protecting and restoring natural wetlands
      in China. The spatial differences in natural wetland-farmland conversions among
      different geographic regions and climatic zones suggest that China must develop
      place-based sustainable management policies and plans for natural wetlands. This
      study provides important scientific information necessary for developing such
      policies and implementation plans.

PMID- 29635191
TI  - Dimensional changes of the carpal tunnel and the median nerve during manual
      mobilization of the carpal bones.
AB  - INTRODUCTION: The carpal tunnel is a clinically important fibro-osseous conduit
      for the median nerve and associated tendons. It is mechanically dynamic, such
      that the dimensions of the tunnel and median nerve change with position, movement
      and application of externally applied force with mechanical devices. Therapeutic
      manual techniques that appear to move and change tunnel shape are part of
      clinical practice. The aim of this study was therefore to measure changes in
      dimensions of the carpal tunnel and median nerve with manual mobilization of the
      carpal bones. MATERIAL AND METHODS: An analytical descriptive study with 18
      volunteer subjects and a total of 33 records was designed. Ultrasound
      measurements of the cross-sectional area (CSA), anteroposterior diameter (APD),
      transverse diameter (TD), perimeter, flattening ratio and circularity of the
      carpal tunnel and of the median nerve, were measured, both in the anatomical
      position of the wrist and during mobilization techniques of the carpal bones.
      RESULTS: During the mobilization technique, the tunnel (p = 0.003) CSA
      significantly increased. APD also increased significantly for the tunnel (<0.001)
      while TD decreased. The median nerve showed similar and significant (p < 0.001)
      changes than the tunnel. However, because several of the obtained differences
      where smaller than the SDD obtained in a previous study, these differences were
      considered as irrelevant. CONCLUSIONS: Manual mobilization of the carpal bones
      produced significant changes in the dimensions of the carpal tunnel.

PMID- 29635195
TI  - Driving forces and their contribution to the recent decrease in sediment flux to
      ocean of major rivers in China.
AB  - Understanding the mechanisms behind land-ocean sediment transport processes is
      crucial, due to the resulting impacts on the sustainable management of water and
      soil resources. This study investigated temporal trends and historical phases of
      sediment flux delivered to the sea by nine major rivers in China, while also
      quantifying the contribution of key anthropogenic and natural driving forces.
      During the past six decades, sediment flux from these nine major rivers exhibited
      a statistically significant negative trend, decreasing from 1.92Gtyr-1 during
      1954-1968 to 1.39Gtyr-1, 0.861Gtyr-1 and 0.335Gtyr-1 during 1969-1985, 1986-1999
      and 2000-2016, respectively. We used a recently developed Sediment Identity
      approach and found that the sharp decrease in sediment load observed across China
      was mainly (~95%) caused by a reduction in sediment concentration. Reservoir
      construction exerted the strongest influence on land-ocean sediment fluxes, while
      soil conservation measures represented a secondary driver. Before 1999, soil
      erosion was not controlled effectively in China and reservoirs, especially large
      ones, played a dominant role in reducing riverine sediments. After 1999, soil
      erosion has gradually been brought under control across China, so that
      conservation measures directly accounted for ~40% of the observed decrease in
      riverine sediments. With intensifying human activities, it is predicted that the
      total sediment flux delivered to the sea by the nine major rivers will continue
      to decrease in the coming decades, although at a slower rate, resulting in severe
      challenges for the sustainable management of drainage basins and river deltas.

PMID- 29635200
TI  - Temporal change in the impacts of ambient temperature on preterm birth and
      stillbirth: Brisbane, 1994-2013.
AB  - BACKGROUND: Pregnant women are susceptible to ambient temperature which may
      associate with adverse birth outcomes. These associations might change over time
      due to adaptation. However, no evidence is available worldwide. OBJECTIVES: To
      examine the effects of ambient temperature at three trimesters of pregnancy on
      preterm birth and stillbirth, and evaluate the effect changes during 1994-2013.
      METHODS: Information on birth outcomes and meteorological parameters during 1994
      2013 were obtained in Brisbane, Australia. Cox proportional hazards models were
      employed to evaluate the effects of mean temperature during each trimester of
      pregnancy on preterm birth and stillbirth. An interaction term between time and
      temperature was used to assess the potential changes in effects of temperature
      over time. RESULTS: Both low and high temperatures at the 3rd trimester of
      pregnancy significantly increased the risk of preterm birth, with similar hazard
      ratios (HRs) [95% confidence intervals (CIs)] for low [1.21 (1.16, 1.27)] and
      high [1.21 (1.16, 1.26)] temperatures in comparison with thresholds. Increased
      risk of stillbirth was significantly associated with both low and high
      temperatures at the 2nd trimester of pregnancy, and lower HRs were observed for
      low temperature [1.23 (1.04, 1.45)] than high temperature [1.47 (1.24, 1.74)], in
      comparison with thresholds. The effects of low temperature became stronger,
      whereas the effects of high temperature became weaker from 1994 to 2013 for both
      preterm birth and stillbirth. CONCLUSIONS: Both low and high ambient temperatures
      during pregnancy increase the risks of preterm birth and stillbirth. Pregnant
      women should have adapted to high temperature but not low temperature.

PMID- 29635192
TI  - Enterobacter aerogenes metabolites enhance Microcystis aeruginosa biomass
      recovery for sustainable bioflocculant and biohydrogen production.
AB  - We report a recycling bioresource involving harvesting of Microcystis aeruginosa
      using the bioflocculant (MBF-32) produced by Enterobacter aerogenes followed by
      the recovery of the harvested M. aeruginosa as the main substrate for the
      sustainable production of MBF-32 and biohydrogen. The experimental results
      indicate that the efficiency of bioflocculation exceeded 90% under optimal
      conditions. The harvested M. aeruginosa was further recycled as the main
      substrate for the supply of necessary elements. The highest yield (3.6+/-0.1g/L)
      of MBF-32 could be obtained from 20g/L of wet biomass of M. aeruginosa with an
      additional 20g/L of glucose as the extra carbon source. The highest yield of
      biohydrogen was 35mL of H2/g (dw) algal biomass, obtained from 20g/L of wet
      biomass of M. aeruginosa with an additional 10g/L of glycerol. Transcriptome
      analyses indicated that MBF-32 was mainly composed of polysaccharide and
      tyrosine/tryptophan proteins. Furthermore, NADH synthase and polysaccharide
      export-related genes were found to be up-regulated.

PMID- 29635198
TI  - Fading positive effect of biochar on crop yield and soil acidity during five
      growth seasons in an Indonesian Ultisol.
AB  - Low fertility limits crop production on acidic soils dominating much of the humid
      tropics. Biochar may be used as a soil enhancer, but little consensus exists on
      its effect on crop yield. Here we use a controlled, replicated and long-term
      field study in Sumatra, Indonesia, to investigate the longevity and mechanism of
      the effects of two contrasting biochars (produced from rice husk and cacao shell,
      and applied at dosages of 5 and 15tha-1) on maize production in a highly acidic
      Ultisol (pHKCl3.6). Compared to rice husk biochar, cacao shell biochar exhibited
      a higher pH (9.8 vs. 8.4), CEC (197 vs. 20cmolckg-1) and acid neutralizing
      capacity (217 vs. 45cmolckg-1) and thus had a greater liming potential. Crop
      yield effects of cacao shell biochar (15tha-1) were also much stronger than those
      of rice husk biochar, and could be related to more favorable Ca/Al ratios in
      response to cacao shell biochar (1.0 to 1.5) compared to rice husk biochar (0.3
      to 0.6) and nonamended plots (0.15 to 0.6). The maize yield obtained with the
      cacao shell biochar peaked in season 2, continued to have a good effect in
      seasons 3-4, and faded in season 5. The yield effect of the rice husk biochar was
      less pronounced and already faded from season 2 onwards. Crop yields were
      correlated with the pH-related parameters Ca/Al ratio, base saturation and
      exchangeable K. The positive effects of cocoa shell biochar on crop yield in this
      Ultisol were at least in part related to alleviation of soil acidity. The fading
      effectiveness after multiple growth seasons, possibly due to leaching of the
      biochar-associated alkalinity, indicates that 15tha-1 of cocoa shell biochar
      needs to be applied approximately every third season in order to maintain
      positive effects on yield.

PMID- 29635201
TI  - Bioelectricity production from wood hydrothermal-treatment wastewater: Enhanced
      power generation in MFC-fed mixed wastewaters.
AB  - Electrogenic microorganisms are the heart of microbial fuel cell (MFC) systems
      that enable the conversion of waste into bioelectricity. Bacteria able to
      generate current, found in various natural and anthropogenic environments, need
      simple substrates such as acetate or glucose. Complex substrates are utilized by
      bacterial consortia made up of strains that exhibit a wide range of enzymatic and
      metabolic activity that determines the type of substrate they are able to
      degrade. The characteristics of the environment that a bacterial consortium
      develops in strongly affect the consortium's species composition and electrogenic
      potential. This study presents the first attempt to use industrial raw wastewater
      from the hydrothermal treatment of wood (WHTW) as a substrate and a source of
      bacterial consortia for MFC, so that such wastewater could simultaneously be
      treated and produce bioelectricity. The power generated in MFCs fed with WHTW was
      enhanced remarkably from 70 to 360mW/m2 when municipal wastewater was introduced
      into the reactor. An analysis of the bacterial composition of these two types of
      wastewater revealed that the WHTW was dominated by the genera
      Thermoanaerobacterium and Paenibacillus while in the biofilm developed in the
      anode the main genera were Hydrogenophilus and Anaerobaculum. It has been shown
      for the first time that highly polluted wood industry wastewater may be
      effectively treated in MFC systems and the use of appropriate bacterial
      consortium may result in enhancing power generation accompanying wastewater
      treatment.

PMID- 29635202
TI  - Effects of biochar input on the properties of soil nanoparticles and
      dispersion/sedimentation of natural mineral nanoparticles in aqueous phase.
AB  - Upon addition to or otherwise entering soils and waters, biochar particles
      inevitably interact with natural mineral nanoparticles (NPs). We explored the
      impacts of two biochars made from charring peanut shells at 300 and 600 degrees C
      (P300 and P600) on the characteristics of soil NPs extracted from brown soil and
      laterite soil. The dispersion or sedimentation of montmorillonite (Mon),
      kaolinite (Kao), goethite (Goe), and hematite (Hem) in the aquatic phase were
      investigated in the presence of P300 and P600 or their nano samples (NP300 and
      NP600). P300 and P600 increased the organic C fraction in the soil NPs extracted
      from brown soil, and decreased the amount of Fe-associated NPs. However, no
      significant influence was observed in the organic C and mineral phases of
      laterite soil NPs by P300 and P600. Goe and Hem were slightly adsorbed to P300 at
      pH6.5, while Goe or Hem homoaggregates formed and settled onto P600. NP300 and
      NP600 significantly reduced the dispersion of Goe and Hem in the aquatic
      environment via heteroaggregation, but there was no interaction between NP300 or
      NP600 and Mon or Kao. These findings are helpful for understanding the
      interaction between natural minerals and biochars, and the potential fate and
      ecological services of biochar-mineral complexes in soil and water.

PMID- 29635194
TI  - Maternal exposure to nonylphenol during pregnancy and lactation induces
      microglial cell activation and pro-inflammatory cytokine production in offspring
      hippocampus.
AB  - Recently, environmental nonylphenol (NP) exposure in the fetus and child has
      received increasing attention because of its potentially deleterious effects on
      the central nervous system (CNS). Microglia (MG), resident immune cells in the
      CNS, are vital to CNS homeostasis and defense against exogenous chemicals, which
      makes them a potentially sensitive target of NP. The present study aims to
      explore the effects of maternal NP exposure during pregnancy and lactation on MG
      in offspring hippocampus, the production of pro-inflammatory cytokines by MG, and
      associated underlying mechanisms. We found that maternal NP exposure increased
      the production of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and tumor
      necrosis factor-alpha (TNF-alpha) in offspring hippocampus. Increases in both
      activation and number of MG were observed in offspring hippocampus. Increased
      phosphorylation of Akt was found to co-localize with hippocampal MG, while
      increased phosphorylation of c-Jun N-terminal kinase (JNK), and p38 mitogen
      activated protein kinase (MAPK) were observed in offspring hippocampus. Activator
      protein 1 (AP-1), an inflammatory transcription factor, was also activated in the
      hippocampus of pups subjected to maternal NP exposure. These results suggest that
      maternal NP exposure might activate MG in offspring hippocampus. This activation
      seems to subsequently increase the production of IL-1beta, IL-6, and TNF-alpha.
      Furthermore, Akt/MAPK/AP-1 signaling may be involved in this activation of MG and
      increased production of pro-inflammatory cytokines.

PMID- 29635203
TI  - Pharmaceuticals and illicit drugs - A new threat to the application of sewage
      sludge in agriculture.
AB  - The occurrence of 93 pharmaceuticals, illicit drugs and their metabolites has
      been investigated in stabilized sewage sludge from five municipal wastewater
      treatment plants (WWTPs) in the Slovak Republic. The total population connected
      to the tested WWTPs was approximately 600,000 p.e. which represents >20% of the
      Slovak population connected to public sewer systems. The sludge production from
      the five tested plants was >8100tons in 2016, which is approximately 15% of the
      total Slovak sewage sludge production in 2016. The highest total concentration of
      all pharmaceuticals was found in WWTP Bratislava Devinska Nova Ves (DNV) and
      Senec - 11,800 and 11,300ng/g dry matter (DM), respectively. Among individual
      pharmaceuticals, the highest concentrations were recorded for fexofenadine (mean
      2340ng/g DM, maximum 5600ng/g DM in Bratislava DNV) and telmisartan (mean
      1170ng/g DM, with a maximum of 3370ng/g DM in Senec). A principal component
      analysis revealed differences between pharmaceutical patterns in aerobically and
      anaerobically stabilized sludge. The worst-case scenario based on no further
      degradation of pharmaceuticals between sludge production and field application
      was used to predict pharmaceutical mass loads in agriculture. For the result, we
      estimated an annual load to soil in the Slovak Republic of up to several hundred
      kilograms of pharmaceuticals and drugs, with the maximum for fexofenadine
      (120kg/year) and verapamil (29kg/year).

PMID- 29635196
TI  - Presence of pharmaceuticals in fish collected from urban rivers in the U.S. EPA
      2008-2009 National Rivers and Streams Assessment.
AB  - Fish are good indicators of aquatic environment pollution because of their
      capability to uptake pollutants contained in water. Therefore, accumulation of
      pharmaceutical compounds in freshwater and marine fish and other aquatic
      organisms has been studied extensively in the last decade. In this context, the
      present study investigates the occurrence of pharmaceutical compounds in wild
      fish from 25 polluted river sites in the USA, downstream from wastewater
      treatment plants (WWTPs). Sample sites constitute a subset of urban rivers
      investigated in the U.S. EPA's 2008-2009 National Rivers and Streams Assessment.
      Thirteen pharmaceuticals (out of the twenty compounds analyzed) were quantified
      in fish fillets at concentrations commonly below 10ngg-1, in accordance with the
      findings from previous studies in the USA and Europe. The psychoactive drugs
      venlafaxine, carbamazepine and its metabolite 2-hydroxy carbamazepine were the
      most prevalent compounds (58%, 27% and 42%, respectively). This group of drugs is
      highly prescribed and rather resistant to degradation during conventional
      treatment in WWTPs as well as in natural aquatic environments. Salbutamol, a drug
      used to treat asthma, and the diuretic hydrochlorothiazide were also frequently
      detected (in >20% of the samples). Occurrence of six pharmaceutical families due
      to chronic exposure at environmental concentrations in water was detected in
      eight fish species.

PMID- 29635199
TI  - Genetic polymorphisms are associated with exposure biomarkers for metals and
      persistent organic pollutants among Inuit from the Inuvialuit Settlement Region,
      Canada.
AB  - BACKGROUND: Inuit are exposed to some of the highest levels of contaminants
      worldwide. Studies suggest that several genes that mediate the metabolism of
      these contaminants are polymorphic. We hypothesize that single nucleotide
      polymorphisms (SNPs) in such genes may underline differences in biomarker
      concentrations and/or modify exposure-biomarker associations. METHODS: Members
      from the Inuvialuit Settlement Region (Canada) were recruited. Blood
      concentrations of mercury (Hg), cadmium (Cd), lead (Pb),
      dichlorodiphenyldichloroethylene (DDE), and polychlorinated biphenyl (PCB-153)
      were measured. SNPs from pathways such as glutathione, metallothionein, oxidative
      stress, and xenobiotic transport were genotyped in 281 participants, and data
      from 112 SNPs were included in the analyses. Surveys were administered to obtain
      information on demographics, and key sources of Hg (diet) and Cd (smoking)
      exposure. ANOVA and linear regressions were used for data analyses. RESULTS:
      Geometric mean concentrations of metals were 4.6MUg/L for Hg, 1.3MUg/L for Cd,
      and 32.2MUg/L for Pb. Concentrations of organic pollutants were 2.0MUg/L for DDE
      and 0.6MUg/L for PCB-153. Biomarker levels for Hg, Cd, Pb, DDE, and PCB-153
      differed (p<0.05) by genotype for 4, 3, 4, 3, and 3 SNPs, respectively. In
      multivariable analyses (for Pb, DDE, PCB-153) adjusting age, sex and body mass
      index (BMI), only 2 associations (one for Pb and one for DDE) remained
      significant. In multivariable analyses accounting for sources of Hg or Cd
      exposure, 24 SNPs (9 for Hg, 15 for Cd with 4 overlapping) had significant
      (p<0.05) main effects on biomarker levels and/or modified exposure-biomarker
      associations. CONCLUSION: The findings suggest that polymorphisms in key
      environmentally responsive genes can influence biomarker levels and/or modify
      exposure-biomarker associations for contaminants of concern to Arctic
      populations. Consideration of such gene-environment results may help improve the
      ability to conduct exposure (and ultimately risk) assessments of country foods
      and Inuit health.

PMID- 29635204
TI  - Enhanced performance and microbial community analysis of bioelectrochemical
      system integrated with bio-contact oxidation reactor for treatment of wastewater
      containing azo dye.
AB  - Feasibility and superiority of the bioelectrochemical system integrated with
      biocontact oxidation (BES-BCO) for degradation and/or mineralization of azo dyes
      have been confirmed. In this study, the effects of hydraulic retention time
      (HRT), applied voltage, and dissolved oxygen (DO) concentration at the bioanode
      on the performance of BES-BCO and traditional BES were investigated. Using the
      response surface methodology, the optimum values of HRT, applied voltage, and DO
      concentration at the bioanode of BES-BCO were investigated to obtain the maximum
      decolouration and COD removal efficiency and minimum specific energy consumption
      (SEC). The microbial community structure in BES-BCO was studied for analyzing the
      change following the introduction of oxygen. The optimised solution was an
      applied voltage of 0.59V, HRT of 12h, and DO concentration of 0.96mg/L at the
      bioanode. Under such conditions, the DE, COD removal efficiency, and SEC values
      were 94.62+/-0.63%, 89.12+/-0. 32%, and 687.57+/-3.86J/g, respectively. In
      addition, after changing from BES to BES-BCO, the bacterial community structure
      of the bioanode underwent significant changes. Several aerobic aniline-degrading
      bacteria and anode-respiration bacteria (ARB) were found to dominate the
      community of the anode biofilm. The results showed that the removal of azo dye
      degradation by-products was closely correlated with the o-bioanode and the BCO
      bacterial community structure.

PMID- 29635205
TI  - Lead modulated Heme synthesis inducing oxidative stress mediated Genotoxicity in
      Drosophila melanogaster.
AB  - The mechanism of lead (Pb) modulated heme synthesis pathway induced oxidative
      stress mediated genotoxicity using standard (ST) and high bioactivation (HB)
      crosses of Drosophila melanogaster was addressed in the present study. Third
      instar larvae derived from the ST or HB crosses were reared in sub lethal
      concentrations of lead acetate (PbAc) treated food media and showed that Pb was
      readily taken up and accumulated in the said crosses. Pb modulated heme synthesis
      was evident by significant reductions of delta-aminolevulinic acid dehydratase
      (delta-ALA-D) and cytochrome P450 (CYP450) and increased accumulation of delta
      aminolevulinic acid (delta-ALA). The results have also demonstrated that Pb
      induced oxidative stress by overproducing reactive oxygen species (ROS) and lipid
      peroxidation (LPO) and depletion of the antioxidant enzymes such as superoxide
      dismutase (SOD), catalase (CAT), glutathione (GSH) and glutathione-s-transferase
      (GST). Wing somatic mutation and recombination test (SMART) using ST and HB
      crosses revealed that Pb is mutagenic and weakly recombinogenic. By employing
      larval hemocytes, there was an increase in percent of tail DNA in alkaline comet
      compared to that of neutral comet revealing the DNA single strand breaks were the
      products of Pb modulated heme synthesis pathway induced oxidative free radicals.
      Based on these findings, it can be concluded that Pb modulated heme synthesis
      pathway induces oxidative stress that mediates the genotoxicity in D.
      melanogaster.

PMID- 29635210
TI  - Evaluation of the Architect HIV Ag/Ab Combo Assay in a low-prevalence setting:
      The role of samples with a low S/CO ratio.
AB  - BACKGROUND: The Architect HIV Ag/Ab Combo Assay, a fourth-generation ELISA, has
      proven to be highly reliable for the diagnosis of HIV infection. However, its
      high sensitivity may lead to false-positive results. OBJECTIVES: To evaluate the
      diagnostic performance of Architect in a low-prevalence population and to assess
      the role of the sample-to-cutoff ratio (S/CO) in reducing the frequency of false
      positive results. STUDY DESIGN: We conducted a retrospective study of samples
      analyzed by Architect between January 2015 and June 2017. Positive samples were
      confirmed by immunoblot (RIBA) or nucleic acid amplification tests (NAATs).
      Different S/CO thresholds (1, 2.5, 10, 25, and 100) were analyzed to determine
      sensitivity, specificity, and negative and positive predictive values (NPV, PPV).
      ROC analysis was used to determine the optimal S/CO. RESULTS: A total of 69,471
      samples were analyzed. 709 (1.02%) were positive by Architect. Of these, 63
      (8.89%) were false-positive results. Most of them (93.65%) were in samples with
      S/CO < 100. However, most confirmations by NAATs (12 out of 19 cases) were also
      recorded for these samples. The optimal S/CO was 2.5, which provided the highest
      area under the ROC curve (0.9998) and no false-negative results. With this S/CO,
      sensitivity and specificity were 100.0%, and PPV and NPV were 95.8% and 100.0%,
      respectively. In addition, the frequency of false-positive results decreased
      significantly to 4.15%. CONCLUSIONS: Although Architect generates a relatively
      high number of false-positive results, raising the S/CO limit too much to
      increase specificity can lead to false-negative results, especially in newly
      infected individuals.

PMID- 29635206
TI  - Exploration of severities of rainfall and runoff extremes in ungauged catchments:
      A case study of Lai Chi Wo in Hong Kong, China.
AB  - Exploration for estimating rainfall and runoff extremes in ungauged catchments is
      challenging since there are no field measurements of rainfall and streamflow for
      confirming study results. This study proposed a systematic approach to tackle the
      challenge, and the approach includes field survey, rainfall data collection,
      frequency analysis, installation of equipment in the study area, and numerical
      modeling. The approach was then applied to the Lai Chi Wo (LCW) catchment in Hong
      Kong, China, in order to evaluate the severity of a rainstorm and flood event
      occurred on 11 May 2014. With the collection of rainfall data from the rain
      gauges near the catchment, the proxy rainfall dataset for LCW was developed.
      Since the time of concentration of the catchment is about 30 to 40min, this study
      derived rainfall intensity duration frequency (IDF) curves for 9 different
      durations (5min, 10min, 15min, 20min, 30min, 45min, 1h, 1.5h, and 1day) and 7
      different return periods (2, 3, 5, 10, 20, 50 and 100years). Further, a
      hydrological model, TOPMODEL, was used to simulate streamflow process; to
      calibrate the model parameters, a rain gauge was set up in the catchment and a
      water level sensor was installed at a control cross-section of the LCW river in
      January 2015, and the recorded rainfall and runoff data were used to calibrate
      the model parameters. Using the proxy rainfall data, this study obtained the
      simulated streamflow for the catchment, and then derived the streamflow peaks for
      7 different return periods (2, 3, 5, 10, 20, 50 and 100years). Since the time of
      concentration of the catchment is less than 1h, this study derived that the
      return periods of the rainstorm on 11 May 2014 for the durations of 30min and 1h
      are 2.4 and 1.9years, respectively; the return period of the daily rainfall is
      9.6years. The return period of the peak flood of the event is 7.0years, and this
      value is between the return periods of the rainfall for the durations of the time
      of concentration and 1day. This study revealed that the severities of rainfall
      and runoff extremes are not consistent but rationally related, and the 1- and 3
      day antecedent rainfalls can considerably influence flood peak severity. Overall,
      to achieve rational prediction of ungauged basin hydrological processes, it is
      fundamental to install measurement equipment and to record rainfall and
      streamflow data. Even though the period of the recorded data in the ungauged
      catchment is short, the observations are necessary for evaluating the proxy data
      quality, and calibrating and validating the numerical model.

PMID- 29635209
TI  - A LC/MS/MS method for determination of tenofovir in human plasma and its
      application to toxicity monitoring.
AB  - Tenofovir disoproxil fumarate is a pro-drug of the active metabolite tenofovir
      widely used against the HIV1, HIV2, and Hepatitis B virus. Several studies have
      been conducted and found kidney injury associated with tenofovir exposure. High
      tenofovir plasma concentration correlated with kidney injury in tenofovir-exposed
      patients. The present study developed and validated a simple and cost-effective
      LC/MS/MS method to determine tenofovir level in human plasma. A small plasma
      volume of 80 MUl is utilized for the sample preparation. The samples were
      separated by Luna C18 (100 mm * 2.0 mm, 3 MUm) using gradient elution with a
      mobile phase consisting of water (containing 0.1% formic acid) and acetonitrile
      (90:10, v/v). The detection was achieved through multiple reaction monitoring
      using positive ionization mode on the triple quadrupole mass spectrometer with a
      run time of 10 min. The monitoring transitions were set at m/z 288.0 -> 176.1 and
      136.1 for tenofovir and m/z 226.1 -> 152.0 for acyclovir (as the internal
      standard). This standard curve was linear from 10 to 640 ng/ml, with the lower
      limit of quantification of 10 ng/ml. The inter- and intra-day precision results
      were less than 12.3% and their accuracies were within the acceptable range of
      84.9-113.1%. The validated method was successfully applied to the study of
      tenofovir induced kidney injury in HIV-1 infected patients taking 300 mg once
      daily for more than 4 weeks.

PMID- 29635207
TI  - Involuntary sterilization among HIV-positive Garifuna women from Honduras seeking
      asylum in the United States: Two case reports.
AB  - Voluntary sterilization is one of the most widely used forms of contraception by
      women worldwide; however, involuntary sterilization is considered a violation of
      multiple human rights and grounds for asylum in the United States. Women have
      been disproportionately affected by this practice. We report two cases of
      involuntary sterilization in HIV-positive Garifuna women from Honduras who sought
      asylum in America and were medically evaluated at the request of their attorneys.
      Key lessons can be drawn from these cases with regard to the importance of
      medical evaluations in establishing persecution. These include the need for a
      detailed account of the events surrounding sterilization, radiologic proof of
      tubal blockage if at all possible, and confirmation of significant and enduring
      mental distress as a result of the involuntary sterilization. Immigration
      attorneys and medical evaluators need to be attuned to the possibility of a
      history of involuntary sterilization among at risk women seeking asylum in the
      United States.

PMID- 29635211
TI  - The paradox of oleuropein increase in harvested olives (Olea europea L.).
AB  - Olives are non-climacteric fruit. In a previous article, oleuropein (OE)
      increased substantially in fresh green olives exposed to 20  degrees C for 7 d,
      but the increases were lower in preharvest treated fruit with an ethylene
      synthesis inhibitor. The present aim was to investigate whether phenolic
      compounds, including OE, were affected by ethylene treatment in green harvested
      olives. Postharvest treatments with the ethylene perception inhibitor, 1 
      methylcyclopropene (1-MCP) at 1.5 MUL L-1 for 12 h, and/or ethylene at 1000 MUL L
      1 at 20  degrees C for up to 10 d were applied to fruits of 'Konservolia'
      cultivar. The results showed that ethylene and/or 1-MCP had similar effects on
      total phenolics (TP), total antioxidant capacity (TAC) and OE and these results
      are revealed for the first time in olives. Ethylene had no effect on green loss,
      but 1-MCP prevented it slightly. In all treated fruit, but not in controls, TP
      and TAC were increased soon after harvest and remained almost stable throughout
      exposure, whereas OE increased in controls and all treated at later stages (as
      confirmed by HPLC-DAD-ESI-MS) independently of degreening. The present
      experiments could be applied to studies of ethylene perception and transcription
      related responses in these non- climacteric fruit. In practice, harvested olives
      do not lose their antioxidant capacity, but the OE elevation in short-stored
      olives at ambient temperature might have an impact on olive products quality.

PMID- 29635208
TI  - Metabolites profile of Gualou Xiebai Baijiu decoction (a classical traditional
      Chinese medicine prescription) in rats by ultra-performance liquid chromatography
      coupled with quadrupole time-of-flight tandem mass spectrometry.
AB  - Gualou Xiebai Baijiu decoction (GLXB), a well-known classic traditional Chinese
      medicine prescription, has been widely used to treat coronary heart diseases for
      thousands of years in Eastern Asian countries due to its remarkable clinical
      effect. However, due to lack of in vivo metabolism research, the chemical
      components responsible for the therapeutic effects still remain unclear. In this
      work, a reliable "representative structure based homologous xenobiotics
      identification" (RSBHXI) strategy based on ultra-performance liquid
      chromatography coupled with quadrupole time-of-flight tandem mass spectrometry
      (UPLC/Q-TOF-MS) were applied to investigate the chemical components in GLXB
      extracts. As a result, 133 chemical components were characterized based on
      summarized fragmentation patterns, of which 41 components were confirmed
      unambiguously with authentic standards. Furthermore, a total of 138 GLXB-related
      xenobiotics were identified or tentatively characterized after oral
      administration of GLXB extracts. Moreover, to better understand the metabolic
      pathways of characteristic components in GLXB, metabolites profiles of five
      steroidal saponins and two flavonoids were performed, respectively. Since the
      metabolic pathways of five representative saponins had been finished in our
      previous study, we focused on the in vivo metabolism of two flavonoids. A total
      of 36 and 20 metabolites were detected in rat biological samples after oral
      administration of luteolin-7-O-beta-D-glucopyranoside and rutin, respectively.
      The results indicated that dehydration, hydrolysis, hydroxylation, methylation,
      glucuronidation and sulfation were the main metabolic reactions, following the
      metabolic soft spots of GLXB-related flavonoids. Taken altogether, this study
      would be helpful for the further pharmacokinetics, pharmacological evaluation and
      quality control of GLXB.

PMID- 29635214
TI  - 3D QSAR studies, molecular docking and ADMET evaluation, using thiazolidine
      derivatives as template to obtain new inhibitors of PIM1 kinase.
AB  - Proviral Integration site for Moloney murine leukemia virus-1 (PIM1) belongs to
      the serine/threonine kinase family of Ca2+-calmodulin-dependent protein kinase
      (CAMK) group, which is involved in cell survival and proliferation as well as a
      number of other signal transduction pathways. Thus, PIM1 is regarded as a
      promising target for treatment of cancers. In the present paper, a three
      dimensional quantitative structure activity relationship (3D-QSAR) and molecular
      docking were performed to investigate the binding between PIM1 and thiazolidine
      inhibitors in order to design potent inhibitors. The comparative molecular
      similarity indices analysis (CoMSIA) was developed using twenty-six molecules
      having pIC50 ranging from 8.854 to 6.011 (IC50 in nM). The best CoMSIA model gave
      significant statistical quality. The determination coefficient (R2) and Leave-One
      Out cross-validation coefficient (Q2) are 0.85 and 0.58, respectively.
      Furthermore, the predictive ability of this model was evaluated by external
      validation((n = 11, R2test = 0.72, and MAE = 0.170 log units). The graphical
      contour maps could provide structural features to improve inhibitory activity.
      Furthermore, a good consistency between contour maps and molecular docking
      strongly demonstrates that the molecular modeling is reliable. Based on these
      satisfactory results, we designed several new potent PIM1 inhibitors and their
      inhibitory activities were predicted by the molecular models. Additionally, those
      newly designed inhibitors, showed promising results in the preliminary in silico
      ADMET evaluations, compared to the best inhibitor from the studied dataset. The
      results expand our understanding of thiazolidines as inhibitors of PIM1 and could
      be of great help in lead optimization for early drug discovery of highly potent
      inhibitors.

PMID- 29635215
TI  - Cannabis and joints: scientific evidence for the alleviation of osteoarthritis
      pain by cannabinoids.
AB  - Cannabis has been used for millennia to treat a multitude of medical conditions
      including chronic pain. Osteoarthritis (OA) pain is one of the most common types
      of pain and patients often turn to medical cannabis to manage their symptoms.
      While the majority of these reports are anecdotal, there is a growing body of
      scientific evidence which supports the analgesic potential of cannabinoids to
      treat OA pain. OA pain manifests as a combination of inflammatory, nociceptive,
      and neuropathic pain, each requiring modality-specific analgesics. The body's
      innate endocannabinoid system (ECS) has been shown to ameliorate all of these
      pain subtypes. This review summarizes the components of the ECS and details the
      latest research pertaining to plant-based and man-made cannabinoids for the
      treatment of OA pain. Recent pre-clinical evidence supporting a role for the ECS
      to control OA pain is described as well as current clinical evidence of the
      efficacy of cannabinoids for treating OA pain in mixed patient populations.

PMID- 29635213
TI  - Fermentation performance optimization in an ectopic fermentation system.
AB  - Ectopic fermentation systems (EFSs) were developed for wastewater treatment.
      Previous studies have investigated the ability of thermophilic bacteria to
      improve fermentation performance in EFS. Continuing this research, we evaluated
      EFS performance using principle component analysis and investigated the addition
      of different proportions of cow dung. Viable bacteria communities were clustered
      and identified using BOX-AIR-based repetitive extragenic palindromic-PCR and 16S
      rDNA analysis. The results revealed optimal conditions for the padding were maize
      straw inoculated with thermophilic bacteria. Adding 20% cow dung yielded the best
      pH values (6.94-8.56), higher temperatures, increased wastewater absorption,
      improved litter quality, and greater microbial quantities. The viable bacteria
      groups were enriched by the addition of thermophilic consortium, and exogenous
      strains G21, G14, G4-1, and CR-15 were detected in fermentation process. The
      proportion of Bacillus species in treatment groups reached 70.37% after
      fermentation, demonstrating that thermophilic bacteria, especially Bacillus, have
      an important role in EFS, supporting previous predictions.

PMID- 29635218
TI  - Validating post-slaughter interventions to produce consistently high quality pork
      cuts from female and immunocastrated male pigs.
AB  - Eating quality attributes of pork loin (M. longissimus thoracis et lumborum) and
      silverside (M. biceps femoris) from female and immunocastrated male carcases hung
      from either the Achilles tendon or aitchbone, aged for either 2 or 7 days post
      slaughter and cooked as roasts, stir fry and steak (loin only) (n = 25/gender)
      was assessed. A positive control treatment of moisture infusion (10% injection
      rate) was applied to Achilles hung sides with cuts aged for 2 d post-slaughter.
      Neither gender nor ageing period influenced consumer sensory scores. Beneficial
      effects of aitchbone hanging on eating quality compared with Achilles hanging
      were largely observed after 2 d ageing, with improvements (P < 0.05) in overall
      liking scores found for loin stir fry and silverside stir fry and roasts. Overall
      liking scores of all cuts, except silverside stir fry, were increased (P < 0.05)
      when moisture infused compared with those from aitchbone-hung sides. However,
      targeted fail rates of <10% were not consistently achieved across all cuts
      evaluated.

PMID- 29635216
TI  - Towards circuit optogenetics.
AB  - Optogenetics neuronal targeting combined with single-photon wide-field
      illumination has already proved its enormous potential in neuroscience, enabling
      the optical control of entire neuronal networks and disentangling their role in
      the control of specific behaviors. However, establishing how a single or a sub
      set of neurons controls a specific behavior, or how functionally identical
      neurons are connected in a particular task, or yet how behaviors can be modified
      in real-time by the complex wiring diagram of neuronal connections requires more
      sophisticated approaches enabling to drive neuronal circuits activity with single
      cell precision and millisecond temporal resolution. This has motivated on one
      side the development of flexible optical methods for two-photon (2P) optogenetic
      activation using either, or a hybrid of two approaches: scanning and parallel
      illumination. On the other side, it has stimulated the engineering of new opsins
      with modified spectral characteristics, channel kinetics and spatial distribution
      of expression, offering the necessary flexibility of choosing the appropriate
      opsin for each application. The need for optical manipulation of multiple targets
      with millisecond temporal resolution has imposed three-dimension (3D) parallel
      holographic illumination as the technique of choice for optical control of
      neuronal circuits organized in 3D. Today 3D parallel illumination exists in
      several complementary variants, each with a different degree of simplicity, light
      uniformity, temporal precision and axial resolution. In parallel, the possibility
      to reach hundreds of targets in 3D volumes has prompted the development of low
      repetition rate amplified laser sources enabling high peak power, while keeping
      low average power for stimulating each cell. All together those progresses open
      the way for a precise optical manipulation of neuronal circuits with
      unprecedented precision and flexibility.

PMID- 29635217
TI  - Prevalence, patterns, and correlates of multiple substance use disorders among
      adult primary care patients.
AB  - BACKGROUND: Addressing multiple substance use disorders (SUDs) in primary care
      based screening and intervention may improve SUD treatment access, engagement,
      and outcomes. To inform such efforts, research is needed on the prevalence and
      patterns of multiple SUDs among primary care patients. METHODS: Data were
      analyzed from a sample of 2000 adult (aged >= 18) primary care patients recruited
      for a multisite National Drug Abuse Treatment Clinical Trials Network (CTN) study
      (CTN-0059). Past-year DSM-5 SUDs (tobacco, alcohol, and drug) were assessed by
      the modified Composite International Diagnostic Interview. Prevalence and
      correlates of multiple versus single SUDs were examined. Latent class analysis
      (LCA) was used to explore patterns of multiple SUDs. RESULTS: Multiple SUDs were
      found among the majority of participants with SUD for alcohol, cannabis,
      prescription opioids, cocaine, and heroin. Participants who were male, ages 26
      34, less educated, and unemployed had increased odds of multiple SUDs compared to
      one SUD. Having multiple SUDs was associated with greater severity of tobacco or
      alcohol use disorder. LCA of the sample identified three classes: class 1 (83.7%)
      exhibited low prevalence of all SUDs; class 2 (12.0%) had high-moderate
      prevalence of SUDs for tobacco, alcohol, and cannabis; class 3 (4.3%) showed high
      prevalence of SUD for tobacco, opioids, and cocaine. LCA-defined classes were
      distinguished by sex, age, race, education, and employment status. CONCLUSIONS:
      Findings suggest that primary care physicians should be aware of multiple SUDs
      when planning treatment, especially among adults who are male, younger, less
      educated, or unemployed. Interventions that target multiple SUDs warrant future
      investigation.

PMID- 29635219
TI  - Proteomic analysis to investigate color changes of chilled beef longissimus
      steaks held under carbon monoxide and high oxygen packaging.
AB  - This study investigated the proteome basis for color stability variations in beef
      steaks packaged under two modified atmosphere packaging (MAP) methods: HiOx-MAP
      (80% O2/20% CO2) and CO-MAP (0.4% CO/30% CO2/69.6% N2) during 15 days of storage.
      The color stability, pH, and sarcoplasmic proteome analysis of steaks were
      evaluated on days 0, 5, 10 and 15 of storage. Proteomic results revealed that the
      differential expression of the sarcoplasmic proteome during storage contributed
      to the variations in meat color stability between the two MAP methods. Compared
      with HiOx-MAP steaks, some glycolytic and energy metabolic enzymes important in
      NADH regeneration and antioxidant processes, antioxidant peroxiredoxins
      (thioredoxin-dependent peroxide reductase, peroxiredoxin-2, peroxiredoxin-6) and
      protein DJ-1 were more abundant in CO-MAP steaks. The over-expression of these
      proteins could induce CO-MAP steaks to maintain high levels of metmyoglobin
      reducing activity and oxygen consumption rate, resulting in CO-MAP steaks
      exhibiting better color stability than HiOx-MAP steaks during storage.

PMID- 29635221
TI  - Changes in length of hospital stay and number of hospitalization before and after
      the administration of three second-generation antipsychotics long-acting
      injections in patients with schizophrenia: Mirror-image study.

PMID- 29635220
TI  - Consumers' perceptions, attitudes and perceived quality of game meat in ten
      European countries.

PMID- 29635212
TI  - SPL7 locally regulates copper-homeostasis-related genes in Arabidopsis.
AB  - In Arabidopsis, a central regulator of copper (Cu) homeostasis is the
      transcription factor SQUAMOSA promoter binding protein-like7 (SPL7). Under Cu
      deficiency, SPL7 induces the expression of miR398, which suppresses the
      expression of the genes CSD1 and CSD2, which encode cytosolic and chloroplastic
      isoforms of Cu/Zn superoxide dismutase, respectively. Consequently, the limited
      Cu is preferentially assigned to plastocyanin, which is essential for
      photosynthetic electron transport. Consistent with this function of miR398
      related to photosynthesis, its expression is strongly induced in leaves. In this
      study, however, we showed that SPL7 was transcribed mainly around the vasculature
      in roots, where Cu levels were likely sensed. To test the possible long-distance
      signaling of Cu availability from roots to shoots, we conducted a series of
      grafting experiments using spl7 mutant and wild-type (WT) plants. Expression of
      Cu-responsive microRNAs and the resulting suppression of CSD1 and CSD2 mRNAs were
      observed in leaves only when the aerial part was from WT plants, in which a low
      level of SPL7 was transcribed also in the vascular tissues. Although local
      sensing of Cu was disturbed in the spl7 mutant, the Cu level was not affected in
      the shoots. SPL7 is expressed in specific cell layers in both roots and shoots
      and locally senses Cu availability, transmitting the information to surrounding
      cells.

PMID- 29635222
TI  - Psychiatric morbidities and risk factors of suicidal ideation among patients
      attending for psychiatric services at a tertiary teaching hospital in Bangladesh.

PMID- 29635223
TI  - Correlates of self-reported, autobiographical, and mini-mental status examination
      defined memory deficits following electroconvulsive therapy in South India.
AB  - BACKGROUND: Cognitive deficits, self-reported or found following
      electroconvulsive therapy (ECT), and their correlates are diverse. Despite the
      characteristics of people receiving ECT in Asia differ widely from the west,
      pertinent research from Asia remains sparse. METHODS: We investigated the
      correlates of self-reported, mini-mental status examination (MMSE) defined, and
      autobiographical memory deficits in a cohort that received ECT in a south Indian
      tertiary-care setting. 76 consecutive consenting people were recruited within
      seven days of completing their ECT course. Memory was assessed by a subjective
      Likert scale, MMSE, and an autobiographical memory scale (AMS). Psychopathology
      was assessed by brief psychiatric rating scale, and serum cortisol levels were
      estimated by chemi-luminescence immunoassays. Relevant sociodemographic and
      clinical data were collected from the participants, and their medical records.
      The correlates were analysed using generalised linear models after adjusting for
      the effects of potential confounders. RESULTS: Self-reported, MMSE-defined, and
      autobiographical memory deficits were present in 27.6% (95%CI 17.6-37.7%), 42.1%
      (95%CI 31.0-53.2%), and 36.8% (95%CI 26.0-47.7%) of participants, respectively.
      Agreement between the memory deficits was poor. Age, less education, duration of
      illness, hypothyroidism, and past history of another ECT course were
      significantly associated with MMSE-defined deficits. Age, anaemia, past ECT
      course, and pre-ECT blood pressure were significantly associated with
      autobiographical memory deficits, while residual psychopathology and cortisol
      levels were significantly associated with self-reported memory deficits.
      CONCLUSION: Self-reported, MMSE-defined, and autobiographical memory deficits are
      common at the completion of ECT course, and their correlates differ. All service
      users receiving ECT need periodic cognitive assessments evaluating multiple
      cognitive domains.

PMID- 29635224
TI  - Enabling physical activity participation for children and youth with disabilities
      following a goal-directed, family-centred intervention.
AB  - BACKGROUND: There is a paucity of research demonstrating the optimisation and
      maintenance of participation outcomes following physical activity interventions
      for children and youth with disabilities. AIM: To evaluate changes in physical
      activity participation in children with disabilities following a goal-directed,
      family-centred intervention at a healthsports centre, and to identify factors
      influencing participation following the intervention. METHODS AND PROCEDURES: A
      mixed methods pre-test post-test cohort design was applied. Recruitment occurred
      over a 12 month period during standard clinical service provision. The Canadian
      Occupational Performance Measure (COPM) was administered to children and parents
      pre (T1) and post-intervention (T2), and at 12 weeks follow-up (T3). Goal
      Attainment Scaling (GAS) was applied to assess outcomes at 12 weeks follow-up (T2
      T3). Qualitative inquiry described barriers to goal attainment at T3. OUTCOMES
      AND RESULTS: Ninety two children with a range of disabilities (mean age 11.1yr;
      49 males) were included in the study. Statistically significant and clinically
      meaningful improvements in parent ratings of COPM performance and satisfaction of
      participation goals were observed following intervention. Ratings at 12 weeks
      follow-up remained significantly higher than baseline, and 32% of children
      attained their COPM-derived GAS goal. Environmental factors were the most
      frequent barrier to goal attainment following intervention. CONCLUSION AND
      IMPLICATIONS: These results provide preliminary evidence for goal-directed,
      family-centred interventions to optimise physical activity participation outcomes
      for children with disabilities.

PMID- 29635226
TI  - The Role of Central Androgen Receptor Actions in Regulating the Hypothalamic
      Pituitary-Ovarian Axis.
AB  - The androgen receptor (AR) is expressed throughout the hypothalamic-pituitary
      gonadal (HPG) axis, and findings from female global AR knockout mice confirm that
      AR-mediated androgen actions play important roles in regulating female
      reproductive function. We generated neuron-specific AR knockout mice (NeurARKO)
      to investigate the functional role of neuronal AR-mediated androgen action in
      regulating the female HPG axis and fertility. Relative to control females,
      NeurARKO females exhibited elevated luteinizing hormone (LH) levels at diestrus
      (p < 0.05) and a compromised serum LH response to ovariectomy and E2 priming (p <
      0.01). Furthermore, NeurARKO females displayed reduced Kiss1 mRNA expression in
      the anteroventral periventricular nucleus at diestrus (p < 0.05) and proestrus (p
      < 0.05), but elevated Kiss1 (p < 0.05) and neurokinin B (Tac2, p < 0.05) mRNA
      expression in the arcuate nucleus at proestrus compared to WT controls. Ovarian
      follicle dynamics were also altered in NeurARKO ovaries at 3 months of age, with
      a significant reduction in large antral follicle numbers at the proestrus stage
      compared to control WT ovaries (p < 0.05). Increased follicular atresia was
      evident in NeurARKO ovaries with a 4-fold increase in unhealthy large preantral
      follicles (p < 0.01). Despite the findings of aberrant neuroendocrine and ovarian
      characteristics in the NeurARKO females, estrous cyclicity and overall fertility
      were comparable between NeurARKO and WT females. In conclusion, our findings
      revealed that selective loss of neuronal AR actions impacts the
      kisspeptin/GnRH/LH cascade leading to compromised ovarian follicle dynamics.

PMID- 29635227
TI  - Focus/Summary.

PMID- 29635225
TI  - Nutrition for Preterm Infants: 75 Years of History.
AB  - As technology has advanced, survival rates of preterm infants have improved
      dramatically. Human milk was the primary source of enteral nutrition during the
      early days of neonatology, but the HIV/AIDS epidemic resulted in an increased use
      of preterm formula. More recently, the benefits of human milk were rediscovered,
      resulting in increased use of donor human milk as well. The awareness that human
      milk does not contain the amounts of nutrients to meet the high requirements of
      infants born premature resulted in the development of human milk fortifiers. The
      development of these fortifiers is still ongoing, as are alternative methods of
      pasteurization of donor milk. Those initiatives will increase the use of human
      milk with consequently short- and long-term benefits for preterm infants.

PMID- 29635228
TI  - Surgical Treatment of Spinal Deformities in Young Paraplegic Children with
      Intraspinal Tumors.
AB  - Bilateral vertical expandable prosthetic titanium rib (VEPTR) treatment using rib
      to-pelvis constructs without touching the spine is a safe surgical technique to
      correct scoliosis while still allowing further MRI or neurosurgical
      interventions. In this retrospective cohort study, 4 paraplegic children with
      spinal deformity after intraspinal tumors and 4 children with neuromuscular
      diseases were compared. VEPTR treatment was able to considerably reduce the main
      scoliotic curve in both patient groups (41 vs. 40%). However, the tumor group
      constantly showed more severe curve progression over time and less favorable
      pelvic obliquity control. In conclusion, bilateral VEPTR can be expected to be
      less satisfying in children with tumors.

PMID- 29635229
TI  - Cyclophosphamide or Rituximab Treatment of Scleritis and Uveitis for Patients
      with Granulomatosis with Polyangiitis.
AB  - PURPOSE: Vision-threatening ocular inflammation can be a devastating complication
      of granulomatosis with polyangiitis (GPA). Here we performed a retrospective
      observational study to describe the safety and efficacy of treating scleritis and
      uveitis with either cyclophosphamide or rituximab in GPA. METHODS: A chart review
      of patients diagnosed with GPA-associated scleritis or uveitis, treated with
      either cyclophosphamide or rituximab as the final therapy at our clinic, was
      conducted. A total of 1 year of follow-up visits was required for inclusion in
      the study. RESULTS: Thirteen patients (19 eyes) suffering from GPA-associated
      scleritis and/or uveitis were identified. As the final therapy, rituximab was
      administered to 9 patients and cyclophosphamide to 4. Mean duration of follow-up
      was 55 months (range 16-23 months). Remission was observed in all patients. Three
      patients had a flare of scleritis after the completion of therapy, and they were
      restarted on their respective agents. One patient had a flare of retinal
      vasculitis during rituximab therapy. One patient on cyclophosphamide experienced
      transient leukopenia. No adverse side effects of rituximab were noted throughout
      the course of treatment. CONCLUSIONS: Cyclophosphamide and rituximab are safe and
      effective agents for controlling scleritis and uveitis associated with GPA, with
      eventual progression towards steroid-sparing remission.

PMID- 29635230
TI  - Cost-Effectiveness of Intensive Short-Term Dynamic Psychotherapy Trial Therapy.

PMID- 29635231
TI  - RANKL Inhibits the Production of Osteoprotegerin from Smooth Muscle Cells under
      Basal Conditions and following Exposure to Cyclic Strain.
AB  - Receptor activator of nuclear factor-kappaB ligand (RANKL) promotes vascular
      calcification, while osteoprotegerin (OPG) opposes it by blocking RANKL activity.
      It remains unclear which vascular cell populations produce and secrete OPG/RANKL.
      This study characterizes the production of OPG/RANKL from human aortic
      endothelial and smooth muscle cells (HAECs and HASMCs) under various conditions.
      HAECs and HASMCs were exposed to inflammatory stimuli (tumor necrosis factor
      alpha or hyperglycemia) or physiological levels of hemodynamic (cyclic) strain.
      After 72 h, both cells and supernatant media were harvested for assessment of
      OPG/RANKL production. Based on initial findings, the experiments involving HASMCs
      were then repeated in the presence of exogenous RANKL. OPG was produced and
      secreted by HASMCs and (to a considerably lesser degree) HAECs under basal
      conditions. Inflammatory stimuli upregulated OPG production in both cell
      populations. Cyclic strain significantly upregulated OPG production in HASMCs.
      Neither cell population produced RANKL. Exposing HASMCs to exogenous RANKL
      inhibited basal OPG production and completely abrogated the strain-mediated
      upregulation of OPG. These data suggest that HASMCs are a significant source of
      OPG within the vasculature but that RANKL, once present, downregulates this
      production and appears capable of preventing the "protective" upregulation of OPG
      seen with HASMCs exposed to physiological levels of cyclic strain.

PMID- 29635233
TI  - The Double Burden of Malnutrition in Countries Passing through the Economic
      Transition.
AB  - Undernutrition in both its acute and chronic forms (wasting and stunting) is
      strongly inversely correlated with the wealth of nations. Consequently, as many
      low- and middle-income countries (LMICs) achieve economic advancement and pass
      through the so-called "nutrition transition," their rates of undernutrition
      decline. Many countries successfully achieved the Millennium Development Goal of
      halving undernutrition and whole continents have been transformed in recent
      decades. The exception is Africa where the slower rates of decline in the
      prevalence of undernutrition has been overtaken by population growth so that the
      absolute number of stunted children is rising. In many regions, economic
      transition is causing a rapid increase in the number of overweight and obese
      people. The rapidity of this rise is such that many nations bear the simultaneous
      burdens of under- and overnutrition; termed the "double burden" of malnutrition.
      This double burden, accompanied as it is by the unfinished agenda of high levels
      of infectious diseases, is crippling the health systems of many LMICs and thus
      requires urgent attention. Although the prognosis looks threatening for many poor
      countries, they have the advantage of being able to learn from the mistakes made
      by other nations that have passed through the transition before them. Concerted
      action across many arms of government would achieve huge future dividends in
      health and wealth for any nations that can grasp the challenge.

PMID- 29635232
TI  - New Innovative Approaches for Difficult Retained Intraocular Foreign Bodies.
AB  - PURPOSE: To describe innovative ways of removal of complicated difficult large
      retained intraocular foreign bodies (RIOFBs). SETTINGS: Both cases were treated
      at Disha Eye Hospitals, Kolkata, a tertiary eye hospital in eastern India.
      METHODS: Innovative approaches were taken to remove 2 difficult RIOFBs. In the
      first case, a large RIOFB was just beyond the posterior exit wound, trapped in
      the sclera. A 23-G MVR blade was used to create multiple radial releasing scleral
      nicks and bimanually moving the RIOFB into the vitreous cavity using a bent-tip
      24G needle and magnet, and the RIOFB was removed through the limbal section. In
      the second case, a 21-mm long thick nail was deeply embedded in the superior
      sclera with partial localised retinal detachment with its bulbous end just behind
      the clear lens. A lasso technique was used to remove the RIOFB without lens
      touch. RESULTS: In the first case, the patient finally achieved logMAR 0.2 vision
      after silicone oil removal and glued scleral fixation of the intraocular lens. In
      the second case, the patient finally achieved logMAR 0.3 vision after silicone
      oil removal and phacoemulsification with intraocular lens implantation.
      CONCLUSION: Each case of RIOFB is unique and challenging. Here, innovative
      techniques are helpful to rescue these difficult RIOFB situations, which can
      result in excellent outcomes.

PMID- 29635234
TI  - Does Dietary Provision of Guanidinoacetic Acid Induce Global DNA Hypomethylation
      in Healthy Men and Women?
AB  - BACKGROUND/AIMS: Guanidinoacetic acid (GAA) is an experimental dietary additive
      and has been reported to induce methyl depletion when provided by the diet.
      However, no study evaluated whether supplemental GAA affects DNA methylation, a
      critical epigenetic process for genome regulation. METHODS: In this open-label,
      repeated-measure interventional trial, we evaluated the impact of 12 weeks of GAA
      supplementation on global DNA methylation in 14 healthy participants (8 women and
      6 men, age 22.2 +/- 2.3 years, body mass index 24.8 +/- 5.7). RESULTS: Dietary
      provision of GAA had no effect on global DNA methylation, with 5-methylcytosine
      (m5C) nonsignificantly increased by 13.4% at postadministration when averaged
      across participants (95% confidence interval -5.5 to 32.3; p = 0.26). Notable DNA
      hypomethylation (corresponding to a 5% drop in m5C) was found in 3 of 14
      participants at follow-up. CONCLUSION: Global DNA methylation seems to be
      unaltered by dietary provision of 3 g of GAA per day for 12 weeks in healthy men
      and women.

PMID- 29635235
TI  - Cranial Irradiation Induces Hypothalamic Injury and Late-Onset Metabolic
      Disturbances in Juvenile Female Rats.
AB  - Cranial radiotherapy is one of the most effective tools for treating children
      with brain tumors. However, radiotherapy-induced late-onset side effects have a
      significant impact on patients' quality of life. The purpose of this study was to
      investigate the effects of irradiation on metabolism and the possible molecular
      and cellular mechanisms behind such effects. Female Wistar rats were subjected to
      a single dose of 6-Gy whole-brain irradiation on postnatal day 11. The animals
      were sacrificed 6 h or 20 weeks after irradiation. Cell death and proliferation,
      microglial activation, and inflammation were analyzed and RNA sequencing was
      performed. We found that irradiation led to a significantly increased body weight
      from 15 weeks (p < 0.05) along with white adipose tissue accumulation and
      adipocyte hypertrophy at 20 weeks, and these changes were accompanied by glucose
      and lipid metabolic disturbances as indicated by reduced glucose tolerance,
      increased insulin resistance, increased serum triglycerides, and an increased
      leptin/adiponectin ratio. Furthermore, irradiation induced cell death, microglial
      activation, inflammation, and persistent astrocyte reactivity in the
      hypothalamus. Hypothalamic transcriptome analysis showed that 865 genes were
      downregulated and 290 genes were upregulated in the irradiated group 20 weeks
      after irradiation, and further pathway analysis showed that the insulin
      resistance-related PI3K-Akt signaling pathway and the energy expenditure-related
      adipocytokine signaling pathway were downregulated. Gene Ontology enrichment
      analysis showed that the expression of fatty acid metabolism-related proteins and
      effector proteins was significantly different in the irradiation group. This
      study demonstrates that ionizing radiation to the juvenile female brain induces
      hypothalamic damage that is likely to be associated with delayed metabolic
      abnormalities, and this critical vulnerability of the hypothalamus to irradiation
      should be taken into consideration in the development of future protective
      strategies for radiotherapy.

PMID- 29635236
TI  - A Preliminary Probe of Personality Predicting Psychotherapy Outcomes:
      Perspectives from Therapists and Their Clients.
AB  - BACKGROUND: It is widely established that personality disorder has as broad
      negative impact on psychotherapy outcomes. Given the increased emphasis on
      dimensional traits for personality pathology in the DSM-5 and the proposal for
      the ICD-11, it is important to understand how traits are linked to treatment
      outcomes. Building on past research with general traits, we hypothesized that
      more nuanced and specific relations would be apparent. Furthermore, much of the
      past research has relied upon self-reports of personality and little is known
      about how ratings from therapists might be related to outcomes. SAMPLING AND
      METHODS: The present paper examined how dimensional traits from the Five-Factor
      Model predicted outcomes in a case series of 54 therapist-client dyads within a
      doctoral training clinic. Importantly, this extends past research as dimensional
      traits were rated by both therapists and clients at intake as well as
      sequentially over the course of therapy. RESULTS: Correlations and regression
      analyses indicated that traits predicted a variety of outcomes including initial
      engagement in treatment as well as overall symptom reduction across therapy.
      Specifically, preliminary evidence suggests that therapist-rated
      conscientiousness at intake was positively related to clients' early engagement
      in therapy. In addition, openness to experience after the 4th session -
      particularly as rated by the client - was predictive of long-term therapy
      outcomes. CONCLUSIONS: Broadly, these results provided preliminary information
      about the promise of dimensional models for improving the clinical utility of
      personality disorder diagnoses. More specifically, these results reinforced the
      relevance of personality assessment during therapy and indicated the potential
      predictive value of ratings by therapists and their clients.

PMID- 29635237
TI  - Maternal Serum Interleukin-6: A Non-Invasive Predictor of Histological
      Chorioamnionitis in Women with Preterm-Prelabor Rupture of Membranes.
AB  - OBJECTIVE: To assess the added value of maternal serum levels of IL-6 in women
      with preterm-prelabor rupture of membranes (PPROM) as a non-invasive test for the
      prediction of histological chorioamnionitis (HCA). METHODS: This was a
      prospective cohort study of pregnant women between 20 + 0 and 36 + 6 weeks of
      gestation with a confirmed diagnosis of PPROM. Logistic regression models were
      created for the prediction of HCA and compared by assessing the improvement in
      their Naegelkerke R2 as a measure of goodness of fit. Predictive performance of
      all models was assessed by receiver operating characteristics curve (ROC)
      analysis and compared by the DeLong method. RESULTS: From 47 women with PPROM, 31
      (66%) developed HCA. Maternal serum IL-6 >=19.5 pg/dL was the best cut-off point
      for the prediction of HCA (OR = 15; 95% CI: 3.6-61; p < 0.01). A model comprising
      maternal characteristics and IL-6 >=19.5 pg/dL showed an area under the curve of
      0.85 (95% CI: 0.74-0.95), significantly improving the previous models of IL-6
      >=19.5 pg/dL (R2: 23.3 vs. 34.1%; p = 0.01) or maternal characteristics (R2: 8.4
      vs. 34.1%; p < 0.01). CONCLUSIONS: A model comprising maternal serum levels of IL
      6 plus maternal characteristics proves to be a good non-invasive predictor of
      HCA.

PMID- 29635238
TI  - Healthy Lifestyle: A Virtue in Search of a Vision.

PMID- 29635239
TI  - Cervical Myelopathy Caused by Invaginated Laminae of the Axis into the Spinal
      Canal in a Pediatric Patient.
AB  - Cervical myelopathy caused by invaginated laminae of the axis is an extremely
      rare entity. Advanced imaging techniques are useful to define this rare pathology
      and site of the spinal canal compression. Surgical removal of the floating
      laminae is commonly an adequate treatment method. Fusion procedures should be
      added in the presence of instability. There are few cases of invaginated
      anomalous laminae of the axis in the literature. In this report, to the best of
      our knowledge having reviewed the literature, the youngest and first female
      patient is presented.

PMID- 29635240
TI  - Heterogeneity in Lung Cancer.
AB  - Lung cancer diagnosis is a challenge since it is also one of the most frequently
      diagnosed cancers. Diagnostic challenges are deeply related to the development of
      personalized therapy and molecular and precise histological characterizations of
      lung cancer. When addressing these features, it is very important to acknowledge
      the issue of tumour heterogeneity, as it imposes several questions. First of all,
      lung cancer is a very heterogeneous disease, at a cellular and histological
      level. Cellular and histological heterogeneity are addressed with emphasis on the
      diagnosis, pre-neoplastic lesions, and cell origin, trying to contribute to a
      better knowledge of carcinogenesis. Molecular intra-tumour and inter-tumour
      heterogeneity are also addressed as temporal heterogeneity. Lung cancer
      heterogeneity has implications in pathogenesis understanding, diagnosis,
      selection of tissue for molecular diagnosis, as well as therapeutic decision. The
      understanding of tumour heterogeneity is crucial and we must be aware of the
      implications and future developments regarding this field.

PMID- 29635241
TI  - Focus/Summary.

PMID- 29635242
TI  - Pulmonary Catherization Data Correlate Poorly with Renal Function in Heart
      Failure.
AB  - BACKGROUND: The mechanisms of renal dysfunction in heart failure are poorly
      understood. We chose to explore the relationship of cardiac filling pressures and
      cardiac index (CI) in relation to renal dysfunction in advanced heart failure.
      OBJECTIVES: To determine the relationship between renal function and cardiac
      filling pressures using the United Network of Organ Sharing (UNOS) pulmonary
      artery catherization registry. METHODS: Patients over the age of 18 years who
      were listed for single-organ heart transplantation were included. Exclusion
      criteria included a history of mechanical circulatory support, previous
      transplantation, any use of renal replacement therapy, prior history of
      malignancy, and cardiac surgery, amongst others. Correlations between serum
      creatinine (SCr) and CI, pulmonary capillary wedge pressure (PCWP), pulmonary
      artery systolic pressure (PASP), and pulmonary artery diastolic pressure (PADP)
      were assessed by Pearson correlation coefficients and simple linear regression
      coefficients. RESULTS: Pearson correlation coefficients between SCr and PCWP,
      PASP, and PADP were near zero with values of 0.1, 0.07, and 0.08, respectively (p
      < 0.0001). A weak negative correlation coefficient between SCr and CI was found
      (correlation coefficient, -0.045, p = 0.027). In a subgroup of young patients
      unlikely to have noncardiac etiologies, no significant correlations between these
      values were identified. CONCLUSION: These findings suggest that, as assessed by
      pulmonary artery catherization, none of the factors - PCWP, PASP, PADP, or CI -
      play a prominent role in cardiorenal syndromes.

PMID- 29635243
TI  - A Novel SCN5A Variant Associated with Abnormal Repolarization, Atrial
      Fibrillation, and Reversible Cardiomyopathy.
AB  - A variety of life-threating arrhythmias are caused by mutations in the cardiac
      voltage-gated sodium channel encoded by the SCN5A gene. In this study, we report
      a novel loss-of-function SCN5A variant, p.Ile1343Val (c.4027A>G), identified in a
      42-year-old proband who presented with an unusual ECG with abnormal
      repolarization with biphasic T-waves in anteroseptal leads, persistent atrial
      fibrillation (AF), intermittent left bundle branch block (LBBB), and reversible
      cardiomyopathy. The patient did not meet the diagnostic criteria for Brugada
      syndrome, long QT syndrome, or any other known SCN5A-associated phenotype.
      Characterization of the biophysical properties of the variant by in vitro patch
      clamp experiments revealed a reduced Na+ current with no effect on the
      inactivation kinetics of the channel. This loss-of-function of Na+ current could
      explain the intermittent LBBB as well as the AF. In conclusion, we describe a
      unique combination of electrical and structural abnormalities associated with a
      novel SCN5A variant. Our findings broaden the spectrum of cardiac phenotypes
      associated with SCN5A channelopathy, underlining the complex clinical
      manifestations of genetic variations within this gene.

PMID- 29635244
TI  - Autophagy Facilitates Metadherin-Induced Chemotherapy Resistance Through the
      AMPK/ATG5 Pathway in Gastric Cancer.
AB  - BACKGROUND/AIMS: Metadherin (MTDH) is overexpressed in some malignancies and
      enhances drug resistance; however, its role in gastric cancer (GC) and the
      underlying mechanisms remain largely unexplored. Here, we explore the mechanism
      by which MTDH induces drug resistance in GC. METHODS: We analysed the level of
      MTDH in GC and adjacent normal gastric mucosal tissues by real-time quantitative
      PCR (q-PCR). We also analysed the level of autophagy by western blot analysis,
      confocal microscopy, and transmission electron microscopy after MTDH knockdown
      and overexpression, and examined fluorouracil (5-FU) resistance by Cell Counting
      Kit-8 at the same time. Finally, GC patient-derived xenograft tumours were used
      to demonstrate 5-FU resistance. An AMPK pathway inhibitor was applied to
      determine the molecular mechanisms of autophagy. RESULTS: MTDH expression was
      significantly increased in the GC specimens compared with that in the adjacent
      normal gastric mucosal tissues. Further study showed a positive correlation
      between the expression level of MTDH and 5-FU resistance. MTDH overexpression in
      MKN45 cells increased the levels of P-glycoprotein (P-gp) and promoted 5-FU
      resistance, while inhibition of MTDH showed the opposite result. The simultaneous
      inhibition of autophagy and overexpression of MTDH decreased the levels of P-gp
      and inhibited 5-FU resistance. Moreover, MTDH induced AMPK phosphorylation,
      regulated ATG5 expression, and finally influenced autophagy, suggesting that MTDH
      may activate autophagy via the AMPK/ATG5 signalling pathway. Our findings reveal
      a unique mechanism by which MTDH promotes GC chemoresistance and show that MTDH
      is a potential target for improved chemotherapeutic sensitivity and GC patient
      survival. CONCLUSIONS: MTDH-stimulated cancer resistance to 5-FU may be mediated
      through autophagy activated by the AMPK/ATG5 pathway in GC.

PMID- 29635245
TI  - Downregulation and Aberrant Localization of Forkhead Box J1 in Allergic Nasal
      Mucosa.
AB  - BACKGROUND: Forkhead box J1 (FOXJ1) plays pivotal roles in motile cilia
      formation. However, it remains unclear whether abnormal expression or
      localization of FOXJ1 in nasal mucosa tissues is associated with allergic
      rhinitis (AR), in which impaired mucociliary clearance is implicated. OBJECTIVE:
      We sought to investigate the expression and localization of FOXJ1 in inferior
      turbinate from patients with AR and controls. METHODS: We assayed mRNA levels of
      FOXJ1, DNAI1, DNALI1, and DNAH9 by using whole-genome expression array and
      quantitative real-time polymerase chain reaction. We elucidated the localization
      of FOXJ1 by using immunofluorescence assays in paraffin sections and primary
      single cells. Four patterns of FOXJ1 localization (normal, N; intermediate, I;
      mislocalization, M; absence, A) were defined. We developed a semiquantitative
      scoring system to elucidate their localization in 5 areas per paraffin section,
      with individual sections being assigned a score between 0 and 2. RESULTS: The
      mRNA levels of FOXJ1, DNAI1, DNALI1, and DNAH9 were significantly reduced in
      patients with AR compared with controls (all p < 0.05). The median (1st and 3rd
      quartile) of the FOXJ1 score was 0.4 (0.0 and 0.85) in patients with AR, and 0.2
      (0.0 and 0.4) in controls (p < 0.05). For primary cytospin samples, the mean
      percentages of FOXJ1 localization patterns N, I, M, and A were 46.7, 10.0, 30.0,
      and 26.7% in patients with AR, and 82.5, 5.0, 5.0, and 7.5% in controls,
      respectively (p < 0.05). CONCLUSION: Downregulation and aberrant localization of
      FOXJ1 may be crucial characteristics of the allergic nasal mucosa.

PMID- 29635246
TI  - Endocranial Development in the Coyote (Canis latrans) and Gray Wolf (Canis
      lupus): A Computed Tomographic Study.
AB  - The purpose of this study was to examine the pattern of postnatal brain growth in
      two wild canid species: the coyote (Canis latrans) and gray wolf (Canis lupus).
      Adult regional and total brain volume differences were also compared between the
      two species as well as within each species by sex. Three-dimensional virtual
      endocasts of endocranial airspace were created from computed tomography scans of
      52 coyote skulls (28 female, 24 male; 1 day to 13.4 years) and 46 gray wolf
      skulls (25 female, 21 male; 1 day to 7.9 years). Age was known in coyotes or
      estimated from dentition patterns in wolves. The 95% asymptotic growth of the
      endocranium is completed by 21 weeks in male and 17.5 weeks in female coyotes and
      by 27 weeks in male and 18.5 weeks in female wolves. These ages are well before
      age at first reproduction (coyote - 40.4 weeks; wolf - 91.25 weeks). Skull growth
      as measured by centroid size lags behind endocranial growth but is also completed
      before sexual maturity. Intra- and interspecific comparisons of brain volumes in
      the adult wolves and coyotes revealed that relative anterior cerebrum (AC) volume
      was greater in males than females in both species. Relative brain size was
      greater in the coyote than in the wolf as was relative cerebrum volume. However,
      relative AC volume and relative cerebellum and brainstem volume was greater in
      the wolf than coyote. One explanation for the increased AC volume in males
      compared to females may be related to the role of social information processing.
      However, additional data are needed to determine the correspondence between
      regional volumes and functional differences either between or within these
      species. Nonetheless, these findings provide important baseline data for further
      studies on wild canid brain variations and development.

PMID- 29635248
TI  - Chromosomal Mapping of Repeat DNA in Bergiaria westermanni (Pimelodidae,
      Siluriformes): Localization of 45S rDNA in B Chromosomes.
AB  - The occurrence of repetitive DNA in autosomes and B chromosomes of Bergiaria
      westermanni was examined using conventional and molecular cytogenetic techniques.
      This species exhibited 2n = 56 chromosomes, with intra- and interindividual
      variation in the number of heterochromatic B chromosomes (from 0 to 4). The 5S
      rDNA was localized in pairs 1 and 5, and histone probes (H1, H3, and H4) and U2
      small nuclear RNA were syntenic with 5S rDNA in pair 5. Histone sequences were
      also located in chromosome pair 14. The (GATA)n sequence was dispersed throughout
      the autosomes and B chromosomes, with clusters (microsatellite accumulation) in
      some chromosome regions. The telomeric probe revealed no signs of chromosomal
      rearrangements in the genome of B. westermanni. The 45S rDNA sites were detected
      in the terminal region of pair 27; these sites corresponded to a GC-rich
      heterochromatin block. In addition, 3 of the 4 B chromosomes also contained 45S
      rDNA copies. Silver nitrate staining in interphase nuclei provided indirect
      evidence of the expression of these rRNA genes in B chromosomes, indicating the
      probable origin of these elements. This report shows plasticity in the
      chromosomal localization of repeat DNA in B. westermanni and features a
      discussion of genomic diversification.

PMID- 29635247
TI  - Efficacy and Survival Outcome Associated with the Use of Novel Agents and
      Autologous Stem Cell Transplantation in Cases of Immunoglobulin D Multiple
      Myeloma in Korea.
AB  - BACKGROUND: Immunoglobulin D multiple myeloma (IgD MM) is characterized by a poor
      prognosis. Data are lacking on the survival benefits associated with the use of
      novel agents followed by autologous stem cell transplantation (ASCT) in IgD MM
      patients. We evaluated the clinical outcomes of induction treatment with novel
      agents followed by ASCT. METHODS: This was a single-center, retrospective study
      of 22 IgD MM patients who underwent ASCT between 1995 and 2016. Of these, 10
      (45.4%) received novel agents and 12 (54.6%) received nonnovel agents. Clinical
      features and survival outcomes were examined. RESULTS: Median overall survival
      (OS) was 37.7 months in the 22 patients. Those in the novel-agents group received
      bortezomib or thalidomide-based regimens, whereas 91.7% of the nonnovel-agents
      group received a vincristine-based regimen. The median progression-free survival
      and OS in the novel-agent/nonnovel-agent groups were 8.3/7.4 and 38.6/12.5
      months, respectively. The median OS of patients receiving maintenance therapy was
      not reached. CONCLUSION: This study showed improved survival outcomes compared to
      our previous study (37.7 vs. 12 months), suggesting that the use of a novel agent
      as induction and maintenance therapy may be beneficial in patients with IgD MM
      who undergo ASCT.

PMID- 29635249
TI  - Alterations in Heterochromatic Knobs in Maize Callus Culture by Breakage-Fusion
      Bridge Cycle and Unequal Crossing Over.
AB  - The meiotic and mitotic behavior of regenerated plants derived from a long-term
      callus culture, designated 12-F, was analyzed. This culture was heterozygous for
      an amplification of the heterochromatic knob on the long arm of chromosome 7
      (K7L). We aimed to investigate if the amplification resulted from a breakage
      fusion-bridge (BFB) cycle or from unequal sister chromatid recombination.
      Therefore, C-banded mitotic metaphases and pachytene, diakinesis, and anaphase I
      of regenerated plants were analyzed. Additionally, the occurrence of alterations
      in K7L was investigated in C-banded metaphases from short-term callus cultures
      derived from lines related to the donor genotype of the 12-F culture. As a
      result, plants homozygous and heterozygous for the amplification were detected.
      Meiosis was normal with few abnormalities, such as a low frequency of univalents
      at diakinesis. In the callus cultures a chromosome 7 with knobs of different
      sizes in the sister chromatids was detected and interpreted as a result of
      unequal crossing over. Other chromosomal alterations were consistent with the
      occurrence of BFB cycles. The finding of unequal crossing over in the cultures
      supports the conclusion that the amplification in the culture 12-F would be
      derived from this mechanism. If the amplification was derived from a BFB cycle,
      the terminal euchromatic segment between knob and the telomere would be deleted,
      and possibly, homozygous plants would not be viable.

PMID- 29635250
TI  - A Systematic Review of Genetic Testing and Lifestyle Behaviour Change: Are We
      Using High-Quality Genetic Interventions and Considering Behaviour Change Theory?
AB  - BACKGROUND: Studying the impact of genetic testing interventions on lifestyle
      behaviour change has been a priority area of research in recent years.
      Substantial heterogeneity exists in the results and conclusions of this
      literature, which has yet to be explained using validated behaviour change theory
      and an assessment of the quality of genetic interventions. The theory of planned
      behaviour (TPB) helps to explain key contributors to behaviour change. It has
      been hypothesized that personalization could be added to this theory to help
      predict changes in health behaviours. PURPOSE: This systematic review provides a
      detailed, comprehensive identification, assessment, and summary of primary
      research articles pertaining to lifestyle behaviour change (nutrition, physical
      activity, sleep, and smoking) resulting from genetic testing interventions. The
      present review further aims to provide in-depth analyses of studies conducted to
      date within the context of the TPB and the quality of genetic interventions
      provided to participants while aiming to determine whether or not genetic testing
      facilitates changes in lifestyle habits. This review is timely in light of a
      recently published "call-to-action" paper, highlighting the need to incorporate
      the TPB into personalized healthcare behaviour change research. METHODS: Three
      bibliographic databases, one key website, and article reference lists were
      searched for relevant primary research articles. The PRISMA Flow Diagram and
      PRISMA Checklist were used to guide the search strategy and manuscript
      preparation. Out of 32,783 titles retrieved, 26 studies met the inclusion
      criteria. Three quality assessments were conducted and included: (1) risk of
      bias, (2) quality of genetic interventions, and (3) consideration of theoretical
      underpinnings - primarily the TPB. RESULTS: Risk of bias in studies was overall
      rated to be "fair." Consideration of the TPB was "poor," with no study making
      reference to this validated theory. While some studies (n = 11; 42%) made
      reference to other behaviour change theories, these theories were generally
      mentioned briefly, and were not thoroughly incorporated into the study design or
      analyses. The genetic interventions provided to participants were overall of
      "poor" quality. However, a separate analysis of studies using controlled
      intervention research methods demonstrated the use of higher-quality genetic
      interventions (overall rated to be "fair"). The provision of actionable
      recommendations informed by genetic testing was more likely to facilitate
      behaviour change than the provision of genetic information without actionable
      lifestyle recommendations. Several studies of good quality demonstrated changes
      in lifestyle habits arising from the provision of genetic interventions. The most
      promising lifestyle changes were changes in nutrition. CONCLUSIONS: It is
      possible to facilitate behaviour change using genetic testing as the catalyst.
      Future research should ensure that high-quality genetic interventions are
      provided to participants, and should consider validated theories such as the TPB
      in their study design and analyses. Further recommendations for future research
      are provided.

PMID- 29635251
TI  - Clinical, Diagnostic, and Treatment Disparities between HIV-Infected and Non-HIV
      Infected Immunocompromised Patients with Pneumocystis jirovecii Pneumonia.
AB  - The substantial decline in the Pneumocystis jirovecii pneumonia (PCP) incidence
      in HIV-infected patients after the introduction of antiretroviral therapy (ART)
      in resource-rich settings and the growing number of non-HIV-infected
      immunocompromised patients at risk leads to considerable epidemiologic changes
      with clinical, diagnostic, and treatment consequences for physicians. HIV
      infected patients usually develop a subacute course of disease, while non-HIV
      infected immunocompromised patients are characterized by a rapid disease
      progression with higher risk of respiratory failure and higher mortality. The
      main symptoms usually include exertional dyspnea, dry cough, and subfebrile
      temperature or fever. Lactate dehydrogenase may be elevated. Typical findings on
      computed tomography scans of the chest are bilateral ground-glass opacities with
      or without cystic lesions, which are usually associated with the presence of
      AIDS. Empiric treatment should be initiated as soon as PCP is suspected.
      Bronchoalveolar lavage has a higher diagnostic yield compared to induced sputum.
      Immunofluorescence is superior to conventional staining. A combination of
      different diagnostic tests such as microscopy, polymerase chain reaction, and
      (1,3)-beta-D-glucan is recommended. Trimeth-oprim/sulfamethoxazole for 21 days is
      the treatment of choice in adults and children. Alternative treatment regimens
      include dapsone with trimethoprim, clindamycin with primaquine, atovaquone, or
      pentamidine. Patients with moderate to severe disease should receive adjunctive
      corticosteroids. In newly diagnosed HIV-infected patients with PCP, ART should be
      initiated as soon as possible. In non-HIV-infected immunocompromised patients,
      improvement of the immune status should be discussed (e.g., temporary reduction
      of immunosuppressive agents). PCP prophylaxis is effective and depends on the
      immune status of the patient and the underlying immunocompromising disease.

PMID- 29635252
TI  - Study of the Association of PEAR1, P2Y12, and UGT2A1 Polymorphisms with Platelet
      Reactivity in Response to Dual Antiplatelet Therapy in Chinese Patients.
AB  - OBJECTIVES: Genetic variation is thought to contribute to considerable
      interindividual variability in platelet function, and there is a pressing need to
      identify genetic markers that can be used to predict the response to treatment.
      Our study investigated whether PEAR1, P2Y12, and UGT2A1 polymorphisms were
      associated with platelet reactivity in response to dual antiplatelet therapy in
      Chinese patients with acute coronary syndrome. METHODS: Patients with inhibition
      of platelet aggregation (IPA) < 30% after treatment were classified as the high
      platelet reactivity (HPR) group. Patients with IPA > 30% were classified as the
      normal platelet reactivity (NPR) group. ADP-induced platelet aggregation was
      measured by thromboelastography (TEG) platelet-mapping assay. Thirteen single
      nucleotide polymorphisms (SNPs) of PEAR1, P2Y12 and UGT2A1 were genotyped using
      the Mass-ARRAY platform. RESULTS: Seven SNPs were significantly associated with
      ADP-induced platelet aggregation by univariate analysis. Major allele G at
      rs12041331, minor allele G at rs2644592, minor allele C at rs11264580, and minor
      allele C at rs11249454 were significantly associated with HPR, whereas minor
      allele T at rs57731889, minor allele A at rs16863356, and minor allele T at
      rs7634096 were significantly associated with NPR. The mean IPA was significantly
      lower in patients suffering recurrent ischemic events than in patients without
      recurrent events in our study (p = 0.048). CONCLUSIONS: Our findings suggest that
      PEAR1, P2Y12, and UGT2A1 genetic variants may be potential biomarkers that can be
      used to guide clinical applications of clopidogrel and aspirin in Chinese
      patients.

PMID- 29635253
TI  - Prophylactic Chorioretinectomy in Open Ocular Trauma: A Series of 36 Eyes.
AB  - PURPOSE: The aim of this paper was to report the outcomes of prophylactic
      chorioretinectomy in open-globe injuries where a foreign body penetrated the
      choroid or perforated the globe. METHODS: We conducted a retrospective,
      consecutive, noncomparative, and descriptive study of patients registered in the
      ocular trauma database between January 2006 and December 2014, who underwent
      vitrectomy with chorioretinectomy. RESULTS: Thirty-six patients (33 male, 3
      female) with a mean age of 40 years and a median of follow-up of 13 months were
      included. Twenty-one cases had penetrating globe injuries with an intraocular
      foreign body and 15 cases had perforating globe injuries. A concomitant
      chorioretinectomy was performed in all eyes, although it was only partial in 8
      eyes. At the end of follow-up, proliferative vitreoretinopathy (PVR) rates were
      6.5%, anatomical success was 80.6%, and the globe survival rate was 96.8%.
      CONCLUSION: Prophylactic chorioretinectomy is a surgical procedure that may
      decrease posttraumatic PVR, thus improving final visual acuity and increasing
      globe survival rates.

PMID- 29635255
TI  - Central Blood Pressure Parameters Correlate with Cardiac Structure and Function
      in Healthy Chinese Individuals without Cardiovascular Disease.
AB  - PURPOSE: To explore the relationship between central blood pressure (BP)
      parameters and cardiac structure and function parameters in healthy individuals.
      METHODS: Four hundred Chinese participants with no overt cardiovascular disease
      participated in this study. One hundred and seventy-one participants (42.8%) were
      male and the mean age was 60 years. Central BP was measured with the SphygmoCor
      system. Cardiac structure and function were assessed by echocardiography.
      RESULTS: We showed a significant association of left atrial volume and left
      ventricular mass index (LVMI) with brachial and central systolic BP (SBP) and
      pulse pressure (PP; r = 0.189-0.0.39, p < 0.001). Left ventricular diastolic
      function and the E/A ratio were significantly associated with brachial and
      central BP (r = 0.228-0.469, p < 0.001). Multivariate regression analysis
      revealed that central SBP and PP were independently correlated with LVMI after
      normalization for age and other confounding variables (sex, body mass index,
      smoking, and alcohol intake, and the levels of triglycerides, high-density
      lipoprotein, low-density lipoprotein, creatinine, uric acid, fasting blood
      glucose, log C-reactive protein, and fibrinogen. However, only central SBP was
      found to be independently correlated with the E/A ratio. CONCLUSIONS: Cardiac
      structure and diastolic function were associated with brachial and central BP.
      However, after normalization, cardiac structure parameters were independently
      correlated with central SBP and PP. Diastolic function was the only cardiac
      function parameter that correlated with central SBP.

PMID- 29635254
TI  - Specific IgE for Fag e 3 Predicts Oral Buckwheat Food Challenge Test Results and
      Anaphylaxis: A Pilot Study.
AB  - BACKGROUND: Buckwheat (BW) is the source of a life-threatening allergen. Fag e 3
      specific serum IgE (sIgE) is more useful than BW-sIgE for diagnosis; however, it
      is unknown whether Fag e 3-sIgE can predict oral food challenge (OFC) results and
      anaphylaxis. This study aimed to clarify the efficacy of Fag e 3-sIgE in
      predicting OFC results and anaphylaxis. METHODS: We conducted a retrospective
      review of BW- and Fag e 3-sIgE data obtained using the ImmunoCAP(r) assay system
      and fluorescent enzyme-linked immunosorbent assay from children who underwent OFC
      using 3,072 mg of BW protein between July 2006 and March 2014 at Sagamihara
      National Hospital, Kanagawa, Japan. RESULTS: We analyzed 60 patients aged 1.9
      13.4 years (median 6.0 years); 20 (33%) showed objective symptoms upon BW OFC.
      The patients without symptoms had significantly lower Fag e 3-sIgE than those
      with non-anaphylactic (p < 0.001) and anaphylactic reactions to BW (p = 0.004).
      Fag e 3-sIgE was the only tested factor that significantly predicted positive OFC
      results (odds ratio 8.93, 95% confidence interval 3.10-25.73, p < 0.001) and OFC
      induced anaphylaxis (2.67, 1.12-6.35, p = 0.027). We suggest that a threshold Fag
      e 3-sIgE level of 18.0 kUE/L has 95% probability of provoking a positive reaction
      to BW. CONCLUSIONS: Fag e 3-sIgE predicted OFC results and OFC-induced
      anaphylaxis. We further emphasize paying careful attention to the risk of BW OFC
      induced anaphylaxis.

PMID- 29635257
TI  - Characterization of IDH1 p.R132H Mutant Clones Using Mutation-specific Antibody
      in Myeloid Neoplasms.
AB  - Isocitrate dehydrogenase 1 (IDH1) and IDH2 mutations occur in a variety of
      myeloid neoplasms. Immunohistochemistry (IHC)-based direct visualization of
      mutant clones of hematopoietic cells can be useful for rapid diagnostic screening
      and for monitoring treatment response. In this study, we first evaluated the
      sensitivity and specificity of the IDH1 p.R132H mutation-specific antibody by
      IHC. All IDH1 wild type cases (n=11) and IDH1 mutant cases with a non-p.R132H
      mutation (n=30) were negative by IHC, demonstrating 100% antibody specificity.
      All the initial diagnostic specimens with IDH1 p.R132H mutation including acute
      myeloid leukemia (n=30), myelodysplastic syndromes (MDS) (n=10),
      MDS/myeloproliferative neoplasms (MPN) (n=4), and MPN (n=5) were positive by IHC,
      demonstrating 100% antibody sensitivity. Both immature and mature myeloid cells
      showed immunoreactivity. Erythroid precursors, lymphoid cells, endothelial cells,
      and osteoblasts were consistently negative by IHC. We then evaluated the follow
      up specimens with a known IDH1 mutation status including acute myeloid leukemia
      (n=23), MDS (n=2), MDS/MPN (n=2), and MPN (n=2). Thirty-three IDH1 p.R132H mutant
      cases were positive by IHC and 12 IDH1 mutation negative cases were negative by
      IHC. However, IHC reactivity in up to 25% of bone marrow cells was noted in 8 of
      20 polymerase chain reaction-negative cases, all from patients with a known
      history of IDH1 p.R132H mutation indicating sampling error or a sensitivity issue
      with molecular tests. These data indicate that IHC is a highly specific and
      sensitive tool to detect IDH1 p.R132H mutation in bone marrow involved by myeloid
      neoplasms. In addition, IDH1 p.R132H IHC also allows localization and assessment
      of the maturation stage of the clones carrying the mutation.

PMID- 29635258
TI  - The Spectrum of Thyroid Gland Pathology in Carney Complex: The Importance of
      Follicular Carcinoma.
AB  - The initial description of Carney complex (CNC) in 1985 included myxomas, spotty
      skin pigmentation, and endocrine overactivity (of the adrenal, the pituitary, and
      the testis). In 1997, thyroid neoplasms were found in 3 patients with CNC and
      involvement of the gland in the syndrome was apparent. Herein, we describe the
      clinical, pathologic, and follow-up findings in 26 patients with CNC and a
      disorder of the thyroid gland. The patients were predominantly middle-aged women
      with an asymptomatic thyroid mass. Four patients had hyperthyroidism, which was
      caused by follicular hyperplasia in 2 patients and by toxic adenoma in 2 others.
      Pathologic findings included benign lesions (follicular hyperplasia, nodular
      hyperplasia, and follicular adenoma) in 16 patients and carcinomas (follicular or
      papillary) in 10 patients. The follicular carcinomas had unusual features,
      multifocality, bilaterality, and lymph node metastasis. The tumor was fatal in 3
      of 4 patients with a tumor >=3 cm in diameter. One patient had an unusual
      multifocal microscopic follicular hyperplasia. Detection and treatment of the
      thyroid neoplasms in patients with CNC requires long-term follow-up of patients
      with the syndrome.

PMID- 29635259
TI  - Melanocytic Myxoid Spindle Cell Tumor With ALK Rearrangement (MMySTAR): Report of
      4 Cases of a Nevus Variant With Potential Diagnostic Challenge.
AB  - Melanocytic tumors rarely display extensive dermal myxoid deposits except in the
      myxoid variant of melanoma. We describe in 4 patients the unusual association of
      morphologic and genetic features. All cases occurred in males and were located on
      the limbs or proximal girdle area. Age at diagnosis ranged from 8 to 47 years.
      Size ranged from 6 to 11 mm. Microscopic analysis showed compound, but mainly
      dermal melanocytic nevi, all presenting a deep dermal expansion with fascicules
      of amelanotic spindled cells floating in a myxoid background. Cytologic atypia
      and mitotic activity were low. The superficial portion was either of spitzoid or
      nevoid cytology with a limited junctional component. In the initial case, the
      dermal myxoid component was predominant with rare, barely visible, superficial
      melanocytic nests. This peculiar morphology was responsible for a delayed
      diagnostic, which required an extensive panel of antibodies ruling out most,
      potentially myxoid, soft tissue tumors. We later observed the presence of
      similar, but more limited, dermal morphologic features in 3 other cases.
      Immunohistochemistry in the deep myxoid areas was melanA, ALK, SOX10, and MiTF.
      Molecular studies confirmed the ALK rearrangement by an ALK break-apart
      fluorescence in situ hybridization technique and by RNA sequencing. The latter
      identified 4 different 5'-fusion partners. Two gene fusions were undescribed:
      FBXO28(e2)-ALK(e19) and NPAS2(e2)-ALK(e19), and 2 previously described: TPM3(e7)
      ALK(e20) and PPFIBP1(e9)-ALK(e19). No relapse or metastatic evolution was seen
      during follow-up (3 to 24 mo). We denominated this potentially challenging new
      variant of compound nevus linked to a kinase fusion: Melanocytic Myxoid Spindle
      Cell Tumor with ALK Rearrangement.

PMID- 29635260
TI  - Incidence, Risk Factors, and Definition for Nonunion in Pediatric Lateral Condyle
      Fractures.
AB  - INTRODUCTION: Lateral condyle fractures are a common pediatric elbow injury.
      Nonunion is a known complication of this injury but its incidence and causative
      risk factors are unknown. Further, a clear and consistent definition of nonunion
      for pediatric lateral condyle fractures does not exist. The purpose of this study
      is to determine the rate of nonunion, the risk factors associated with it and to
      provide a clear definition. METHODS: A retrospective chart review of all
      pediatric lateral condyle fractures treated at an urban, tertiary pediatric care
      center between 2001 and 2014. Data collected included demographics, Weiss
      classification, type of treatment, follow-up, time from injury to surgery and
      complications. For patients with nonunions, additional treatments and final range
      of motion were also recorded. A nonunion was defined as lack of callus with
      fragment migration by 8 weeks after initiation of treatment. RESULTS: A total of
      530 patients were identified of which 500 were available for review. There were
      7/500 (1.4%) nonunions in the cohort. Nonunion occurred in 1.4% (2/140) of type I
      fractures, 0% (0 /178) of type II fractures, and 3% (5/168) of type III
      fractures. The only significant risk factor for nonunion was the presence of a
      type III fracture (P=0.05). Five patients with nonunion underwent revision
      surgery with a partially threaded cannulated cancellous screw. All of these
      patients went on to union. Four of the 5 patients had their screws removed after
      union. CONCLUSION: Nonunion after pediatric lateral condyle fracture is rare and
      is defined by lack of any callus with fragment migration at 8 weeks. The only
      significant risk factor for nonunion development was the presence of a type III
      fracture. Revision surgery with a partially threaded screw achieved union in all
      cases. LEVEL OF EVIDENCE: Level IV-retrospective case review.

PMID- 29635261
TI  - Residual Equinus After the Ponseti Method: An MRI-based 3-Dimensional Analysis.
AB  - BACKGROUND: Residual equinus deformity is present in up to 20% of clubfeet
      treated by the Ponseti method. These patients may require surgical release to
      restore dorsiflexion. Despite complete posterior release; persistent
      intraoperative equinus may be present and suggest concurrent joint incongruity.
      The purpose of this study was to characterize differences in ankle morphology in
      toddlers with residual equinus following the Ponseti method. METHODS:
      Preoperative magnetic resonance imaging (MRI) data from 10 patients who underwent
      reconstruction (17 feet; 7 bilateral, 3 unilateral clubfeet) for persistent
      equinus were compared with 16 age-matched controls. Through reverse engineering
      software, MRI data were used to generate 3-dimensional (3D) models. Four talus
      based measures were performed on both MRI data and 3D models-neck depth, neck
      angle, width, and length. Models were also used to calculate talus volume and arc
      of curvature (plafond and talar dome). Standard statistical analyses were
      performed. RESULTS: Talus volumes, width, and length were less in clubfeet then
      in control feet. Although some measures were significant there was no mismatch
      with the ankle mortise dimensions or arc curvature that could account for any
      decrease in dorsiflexion. We found that from MRI measures the clubfoot neck depth
      was 2.3 versus 3.6 mm in controls (P<0.001) and from 3D modeling the clubfoot
      neck depth was 2.3 and 3.5 mm in controls (P=0.003). With 3D modeling talus
      clubfoot neck angle was 153.7 versus 140.4 degrees in controls (P=0.01). The
      clubfoot neck angle obtained from MRI measures were also different yet not
      significant [126.6 in clubfeet versus 122.5 degrees in controls (P=0.12)].
      CONCLUSIONS: In comparison to age-matched feet; we have noted a decrease in talar
      neck depth and an obtuse talar neck angle in clubfeet treated in the manner of
      Ponseti. This may result in anterior ankle impingement and be the cause of
      residual equinus despite posterior release. In these procedures, the surgeon
      should recognize this possibility when the amount of dorsiflexion is less than
      expected. LEVEL OF EVIDENCE: Level III-case control study.

PMID- 29635262
TI  - Childhood Obesity is Associated With Osteochondritis Dissecans of the Knee,
      Ankle, and Elbow in Children and Adolescents.
AB  - BACKGROUND: Osteochondritis dissecans (OCD) is a joint disorder of the
      subchondral bone and articular cartilage whose association with obesity in
      children is not clearly known. The purpose of this study was to assess the
      magnitude of the association between childhood obesity and the occurrence of OCD
      of the knee, ankle, and elbow in children. METHODS: A retrospective chart review
      of an integrated health system was performed on OCD patients aged 2 to 19 from
      2007 to 2011, with over 1 million patients in this cohort. Lesion location,
      laterality, and all patient demographics were recorded. The body mass index (BMI)
      for each patient in the cohort was used to stratify patients into 5 weight
      classes (underweight, normal weight, overweight, moderately obese, and extremely
      obese) based on BMI-for-age. The associations between the 5 weight classes and
      OCD of the ankle, knee, and elbow were assessed using multiple logistic
      regression models to estimate odds ratios (OR) and 95% confidence intervals using
      multivariate analysis to adjust for patient demographic variables. RESULTS: In
      total, 269 patients fit the inclusion criteria. Mean BMI, both absolute and
      percentile, was significantly higher for patients with OCD of the knee, elbow,
      and ankle than patients without OCD. In the multivariate analysis, extremely
      obese patients were found to have an increased OR of OCD for all patients, with
      an 86% increased risk of any OCD compared with normal weight patients. In
      addition, assessment by different types of OCD revealed that extremely obese
      patients had an increased OR of OCD of the elbow and ankle individually, with a
      3.1 times increased OCD elbow risk and 3.0 times increased risk of ankle OCD in
      extremely obese patients. Although extremely obese patients did not have a
      statistically significant increased risk of knee OCD, moderately obese patients
      did have a 1.8 times increased risk of knee OCD as compared with normal weight
      children. There were no significantly different risks of any type of OCD seen in
      overweight or underweight patients as compared with normal weight patients.
      CONCLUSIONS: In this population-based cohort study, extreme obesity is strongly
      associated with an increased risk of OCD overall and OCD of the elbow and ankle
      specifically. In addition, moderate obesity is associated with an increased risk
      of knee OCD. All types of OCD were also found to have a significantly greater
      average BMI when compared with patients without OCD. LEVEL OF EVIDENCE: Level IV
      descriptive epidemiology study.

PMID- 29635263
TI  - Delafloxacin (Baxdela)--a new fluoroquinolone antibiotic.

PMID- 29635264
TI  - Secnidazole (Solosec) for bacterial vaginosis.

PMID- 29635265
TI  - Voretigene neparvovec-rzyl (Luxturna) for inherited retinal dystrophy.

PMID- 29635267
TI  - In brief: Two new drugs for AML.

PMID- 29635266
TI  - Dapagliflozin/saxagliptin (Qtern) for type 2 diabetes.

PMID- 29635268
TI  - Comparison table: some systemic fluoroquinolones.

PMID- 29635269
TI  - Comparison table: some antibiotics for MRSA skin and skin structure infections.

PMID- 29635271
TI  - Methodologic weaknesses notwithstanding, can a study examining the association
      between potatoes (or really any food or nutrient) and "all-cause mortality" truly
      tell us anything meaningful?

PMID- 29635270
TI  - Inactive Matrix Gla Protein, Arterial Stiffness, and Endothelial Function in
      African American Hemodialysis Patients.
AB  - BACKGROUND: Matrix Gla protein (MGP) is a vascular calcification inhibitor
      dependent upon vitamin K for activation. Evidence suggests that elevated plasma
      inactive MGP levels (desphospho-uncarboxylated MGP, dp-ucMGP; indicating poorer
      vascular vitamin K status) are associated with greater cardiovascular disease
      (CVD) risk. Despite African Americans experiencing highest rates of kidney
      failure and CVD events, relationships between dp-ucMGP and CVD risk markers have
      not been examined in this population. We investigated vascular vitamin K status
      (via plasma dp-ucMGP) between African American hemodialysis (HD) patients and
      healthy controls, and the associations of dp-ucMGP with arterial stiffness and
      endothelial function in HD patients only. METHODS: In 37 African American HD
      patients and 37 age- and race-matched controls, plasma dp-ucMGP was measured by
      enzyme immunoassay as a marker of vascular vitamin K status. Carotid-femoral
      pulse wave velocity (PWV; arterial stiffness measurement) and brachial artery
      flow-mediated dilation (FMD; endothelial function measurement) were assessed by
      applanation tonometry and ultrasound, respectively, in HD patients only. RESULTS:
      Mean dp-ucMGP levels were 5.6 times higher in HD patients vs. controls (2,139 +/-
      1,102 vs. 382 +/- 181 pmol/l, P < 0.01). Multiple linear regression, adjusting
      for age, sex, dialysis vintage, diabetes mellitus, CVD history, body mass index,
      and blood pressure, revealed that dp-ucMGP was independently related to PWV
      (standardized beta = 0.49) and FMD (standardized beta = -0.53) (both P < 0.01).
      CONCLUSIONS: Our data suggest that the higher plasma dp-ucMGP concentrations
      found in African American HD patients may be associated with greater arterial
      stiffness and endothelial dysfunction.

PMID- 29635272
TI  - Sox17 is essential for proper formation of the marginal zone of extraembryonic
      endoderm adjacent to a developing mouse placental disk.
AB  - In mouse conceptus, two yolk-sac membranes, the parietal endoderm (PE) and
      visceral endoderm (VE), are involved in protecting and nourishing early-somite
      stage embryos prior to the establishment of placental circulation. Both PE and VE
      membranes are tightly anchored to the marginal edge of the developing placental
      disk, in which the extraembryonic endoderm (marginal zone endoderm: ME) shows the
      typical flat epithelial morphology intermediate between those of PE and VE in
      vivo. However, the molecular characteristics and functions of the ME in mouse
      placentation remain unclear. Here, we show that SOX17, not SOX7, is continuously
      expressed in the ME cells, whereas both SOX17 and SOX7 are coexpressed in PE
      cells, by at least 10.5 days postconception. The Sox17-null conceptus, but not
      the Sox7-null one, showed the ectopic appearance of squamous VE-like epithelial
      cells in the presumptive ME region, together with reduced cell density and
      aberrant morphology of PE cells. Such aberrant ME formation in the Sox17-null
      extraembryonic endoderm was not rescued by the chimeric embryo replaced with the
      wild-type gut endoderm by the injection of wild-type ES cells into the Sox17-null
      blastocyst, suggesting the cell autonomous defects in the extraembryonic endoderm
      of Sox17-null concepti. These findings provide direct evidence of the crucial
      roles of SOX17 in proper formation and maintenance of the ME region, highlighting
      a novel entry point to understand the in vivo VE-to-PE transition in the marginal
      edge of developing placenta.

PMID- 29635273
TI  - Quality Control of the Fuzi Lizhong Pill Through Simultaneous Determination of 16
      Major Bioactive Constituents by RRLC-MS-MS.
AB  - Fuzi Lizhong pill (FLP) is used to treat gastritis, and the monarch drug of it is
      Aconiti Lateralis Radix Praeparata (Fuzi, aconite roots) which is a toxic herbal
      medicine. To better control the safety and quality of FLP, an effective method to
      analyze the contents of 16 toxic and bioactive components using rapid resolution
      liquid chromatography-tandem triple-quadrupole mass spectrometer was established.
      The 16 constituents included aconine, mesaconine, hypaconitine, benzoylaconine,
      benzoylmesaconine, benzoylhypaconine, adenosine, liquiritin, liquiritigenin,
      glycyrrhizic acid, isoliquiritigenin, 6-gingerol, atractylenolide III,
      atractylenolide I, atractylenolide II and glycyrrhetic acid. Ideal separation was
      performed using gradient elution in 13 min by optimized conditions. All the
      isomerides were isolated to baseline. The improved method with a polarity switch
      in contiguous time segments could analyze the five types of components, including
      polar and nonpolar compounds, without decreasing sensitivity. The proposed method
      was fully validated. The results revealed that contents of six alkaloids from
      Fuzi were significantly different among the samples. Using the established method
      and multivariate statistical method, the quality consistency of two dosage forms
      of FLP from different companies were analyzed. The optimized method could be used
      for the quality control of FLP and investigate index compound variation between
      two dosage forms.

PMID- 29635274
TI  - Long-term heart-specific mortality among 347 476 breast cancer patients treated
      with radiotherapy or chemotherapy: a registry-based cohort study.
AB  - Aims: Breast cancer survival has improved throughout the last decades, but
      treatment-induced cardiotoxicity remains a major concern. This study aimed to
      investigate competing causes of death and prognostic factors within a large
      cohort of breast cancer patients and to describe the heart-specific mortality in
      relation to the general population. Methods and results: In this registry-based
      cohort study, women diagnosed with breast cancer between 2000 and 2011, who were
      treated with radiotherapy or chemotherapy and followed until 2014, were
      identified from the Surveillance, Epidemiology, and End Results-18 (SEER-18)
      database. Cumulative mortality functions were computed. To investigate heart
      specific mortality relative to the general population, long-term (>=10 years)
      standardized mortality ratios (SMRs) were calculated. Prognostic factors for
      heart-specific mortality were assessed by calculating cause-specific hazard
      ratios (HRcs) with corresponding 95% confidence intervals using the Cox
      proportional hazards regression. Subgroup analysis on intermediate-term mortality
      according to molecular subtypes, for which information was available since 2010,
      was performed. In total, 347 476 breast cancer patients were eligible to be
      included in the study. Among all possible competing causes of death, breast
      cancer accounted for the highest cumulative mortality. Compared with the general
      population, heart-specific mortality of breast cancer patients treated with
      radiotherapy or chemotherapy was lower [SMRoverall 0.84 (0.79-0.90)]. In subgroup
      analysis, human epidermal growth factor receptor 2 (HER2)-positive subtype was
      not associated with increased heart-specific mortality relative to HER2-negative
      patients [HRcs 0.96 (0.70-1.32)]. Conclusion: Heart-specific mortality among
      breast cancer survivors is not increased compared with the general population.
      Human epidermal growth factor receptor 2-positive patients do not have increased
      heart-specific mortality compared to HER2-negative patients.

PMID- 29635275
TI  - Demystifying O-GlcNAcylation: hints from peptide substrates.
AB  - O-GlcNAcylation, analogous to phosphorylation, is an essential post-translational
      modification of proteins at Ser/Thr residues with a single beta-N
      acetylglucosamine moiety. This dynamic protein modification regulates many
      fundamental cellular processes and its deregulation has been linked to chronic
      diseases such as cancer, diabetes and neurodegenerative disorders. Reversible
      attachment and removal of O-GlcNAc is governed only by O-GlcNAc transferase and O
      GlcNAcase, respectively. Peptide substrates, derived from natural O-GlcNAcylation
      targets, function in the catalytic cores of these two enzymes by maintaining
      interactions between enzyme and substrate, which makes them ideal models for the
      study of O-GlcNAcylation and deglycosylation. These peptides provide valuable
      tools for a deeper understanding of O-GlcNAc processing enzymes. By taking
      advantage of peptide chemistry, recent progress in the study of activity and
      regulatory mechanisms of these two enzymes has advanced our understanding of
      their fundamental specificities as well as their potential as therapeutic
      targets. Hence, this review summarizes the recent achievements on this
      modification studied at the peptide level, focusing on enzyme activity, enzyme
      specificity, direct function, site-specific antibodies and peptide substrate
      inspired inhibitors.

PMID- 29635276
TI  - Multilevel Regression and Poststratification: A Modelling Approach to Estimating
      Population Quantities From Highly Selected Survey Samples.
AB  - Large-scale population health studies face increasing difficulties in recruiting
      representative samples of participants. Non-participation, item non-response and
      attrition, when follow-up is involved, often result in highly selected samples
      even in well-designed studies. We aimed to assess the potential value of
      multilevel regression and poststratification, a method previously used to
      successfully forecast US presidential election results, for addressing biases due
      to non-participation in the estimation of population descriptive quantities in
      large cohort studies. The investigation was performed as an extensive case study
      using a large national health survey of Australian males, the Ten to Men study.
      Analyses were performed in the Bayesian computational package RStan. Results
      showed greater consistency and precision across population subsets of varying
      sizes, when compared with estimates obtained using conventional survey sampling
      weights. Estimates for smaller population subsets exhibited a greater degree of
      shrinkage towards the national estimate. Multilevel regression and
      poststratification provides a promising analytic approach to addressing potential
      participation bias in the estimation of population descriptive quantities from
      large-scale health surveys and cohort studies.

PMID- 29635278
TI  - Obtaining a Correct Diagnosis Rapidly in the United States Is Associated With
      Many Barriers Not Present in Other Countries.

PMID- 29635277
TI  - Impact of Public Health Responses During a Measles Outbreak in an Amish Community
      in Ohio: Modeling the Dynamics of Transmission.
AB  - We quantified measles transmissibility during a measles outbreak in Ohio in 2014
      to evaluate the impact of public health responses. Case incidence and the serial
      interval (time between symptom onset in primary cases and secondary cases) were
      used to assess trends in the effective reproduction number R (the average number
      of secondary cases generated per case). A mathematical model was parameterized
      using early R values to determine the size and duration of the outbreak that
      would have occurred if containment measures had not been initiated, as well as
      the impact of vaccination. As containment started, we found a 4-fold decline in R
      (from approximately 4 to 1) over the course of 2 weeks and maintenance of R < 1
      as control measures continued. Under a conservative scenario, the model estimated
      8,472 cases (90% confidence interval (CI): 8,447, 8,489) over 195 days (90% CI:
      179, 223) without control efforts and 715 cases (90% CI: 103, 1,338) over 128
      days (90% CI: 117, 139) when vaccination was included; 7,757 fewer cases (90% CI:
      7,130, 8,365) and 67 fewer outbreak days (90% CI: 48, 98) were attributed to
      vaccination. Vaccination may not account entirely for transmission reductions,
      suggesting that changes in community behavior (social distancing) and other
      control efforts (isolation, quarantining) are important. Our findings highlight
      the benefits of measles outbreak response and of understanding behavior change
      dynamics.

PMID- 29635279
TI  - Ceragenins are active against drug-resistant Candida auris clinical isolates in
      planktonic and biofilm forms.
AB  - Background: Candida auris has emerged as a serious threat to human health. Of
      particular concern are the resistance profiles of many clinical isolates, with
      some being resistant to multiple classes of antifungals. Objectives: Measure
      susceptibilities of C. auris isolates, in planktonic and biofilm forms, to
      ceragenins (CSAs). Determine the effectiveness of selected ceragenins in gel and
      cream formulations in eradicating fungal infections in tissue explants. Materials
      and methods: A collection of 100 C. auris isolates available at CDC was screened
      for susceptibility to a lead ceragenin. A smaller collection was used to
      characterize antifungal activities of other ceragenins against organisms in
      planktonic and biofilm forms. Effects of ceragenins on fungal cells and biofilms
      were observed via microscopy. An ex vivo model of mucosal fungal infection was
      used to evaluate formulated forms of lead ceragenins. Results: Lead ceragenins
      displayed activities comparable to those of known antifungal agents against C.
      auris isolates with MICs of 0.5-8 mg/L and minimum fungicidal concentrations
      (MFCs) of 2-64 mg/L. No cross-resistance with other antifungals was observed.
      Fungal cell morphology was altered in response to ceragenin treatment. Ceragenins
      exhibited activity against sessile organisms in biofilms. Gel and cream
      formulations including 2% CSA-44 or CSA-131 resulted in reductions of over 4 logs
      against established fungal infections in ex vivo mucosal tissues. Conclusions:
      Ceragenins demonstrated activity against C. auris, suggesting that these
      compounds warrant further study to determine whether they can be used for topical
      applications to skin and mucosal tissues for treatment of infections with C.
      auris and other fungi.

PMID- 29635280
TI  - Successful Development by Design of Experiments of a Gas Chromatography Method
      for Simultaneous Analysis of Residual Solvents of Classes 1 and 2.
AB  - In this study, design of experiments (DoE) was employed to develop a single
      injection method using a headspace gas chromatograph with flame ionization
      detector for resolution of residual solvents of United States Pharmacopeia (USP)
      listed classes 1 and 2, against current recommendation of independent injections.
      G43 column (6% cyanopropylphenyl and 94% dimethylpolysiloxane) and nitrogen were
      used as the stationary phase and carrier gas, respectively. Initial temperature,
      hold time, temperature ramp and carrier gas velocity were the critical method
      parameters. Resolution of 1,1,1-trichloroethane and tetrahydrofuan (THF); THF and
      chloroform; benzene and 1,2-dichloroethane (DCE), and 1,2-dimethoxyethane and DCE
      were selected as critical quality attributes. These were optimized by DoE that
      resulted in resolution of >1.34 among various solvents. The separation of all the
      solvents was achieved within total run time of 77 min. A better resolution of
      2.66 was observed in the case of acetonitrile and methylene chloride; there was
      improved Signal/Noise ratio of 8.86 for 1,1,1-trichloroethane; tailing factor for
      pyridine was 1.00, and the method showed acceptable repeatability of peak areas
      (%RSDmax = 11.53) and retention times (%RSDmax = 0.45). Thus, while system
      suitability criteria and validation results very well met the USP requirements,
      the optimized method proposed in this study proved advantageous additionally in
      terms of single injection; short run time, and use of nitrogen as a carrier gas
      instead of costly helium in the USP method.

PMID- 29635281
TI  - Germline genetic variants in somatically significantly mutated genes in tumors
      are associated with renal cell carcinoma risk and outcome.
AB  - Genome-wide association studies (GWAS) have identified 13 susceptibility loci for
      renal cell carcinoma (RCC). Additional genetic loci of risk remain to be
      explored. Moreover, the role of germline genetic variants in predicting RCC
      recurrence and overall survival (OS) is less understood. In this study, we
      focused on 127 significantly mutated genes from The Cancer Genome Atlas (TCGA)
      Pan-Cancer Analysis across 12 major cancer sites to identify potential genetic
      variants predictive of RCC risk and clinical outcomes. In a three-phase design
      with a total of 2657 RCC cases and 5315 healthy controls, two single nucleotide
      polymorphisms (SNPs) that map to PIK3CG (rs6466135:A, ORmeta = 0.85, 95% CI =
      0.77-0.94, Pmeta = 1.4 * 10-3) and ATM (rs611646:T, ORmeta = 1.17, 95% CI = 1.05
      1.31, Pmeta = 3.5 * 10-3) were significantly associated with RCC risk. With
      respect to RCC recurrence and OS, two separate datasets with a total of 661
      stages I-III RCC patients (discovery: 367; validation: 294) were analyzed. The
      most significant association was observed for rs10932384:C (ERBB4) with both
      outcomes (recurrence: HRmeta = 0.52, 95% CI = 0.39-0.68, Pmeta = 3.81 * 10-6; OS:
      HRmeta = 0.50, 95% CI = 0.37-0.67, Pmeta = 6.00 * 10-6). In addition, six SNPs
      were significantly associated with either RCC recurrence or OS but not both
      (Pmeta < 0.01). Rs10932384:C was significantly correlated with mutation frequency
      of ERBB4 in clear cell RCC (ccRCC) patients (P = 0.003, Fisher's exact test). Cis
      eQTL was observed for several SNPs in blood/transformed fibroblasts but not in
      RCC tumor tissues. In summary, we identified promising genetic predictors of
      recurrence and OS among RCC patients with localized disease.

PMID- 29635283
TI  - Errata.

PMID- 29635282
TI  - Distinct child-to-adult body mass index trajectories are associated with
      different levels of adult cardiometabolic risk.
AB  - Aims: The relationship between life-course body mass index (BMI) trajectories and
      adult risk for cardiovascular disease (CVD) is poorly described. In a
      longitudinal cohort, we describe BMI trajectories from early childhood to
      adulthood and investigate their association with CVD risk factors [Type 2
      diabetes mellitus (T2DM), high-risk lipid levels, hypertension, and high carotid
      intima-media thickness (cIMT)] in adulthood (34-49 years). Methods and results:
      Six discrete long-term BMI trajectories were identified using latent class growth
      mixture modelling among 2631 Cardiovascular Risk in Young Finns Study
      participants (6-49 years): stable normal (55.2%), resolving (1.6%), progressively
      overweight (33.4%), progressively obese (4.2%), rapidly overweight/obese (4.3%),
      and persistent increasing overweight/obese (1.2%). Trajectories of worsening or
      persisting obesity were generally associated with increased risk of CVD outcomes
      in adulthood (24-49 years) [all risk ratios (RRs) >15, P < 0.05 compared with the
      stable normal group]. Although residual risk for adult T2DM could not be
      confirmed [RR = 2.6, 95% confidence interval (CI) = 0.14-8.23], participants who
      resolved their elevated child BMI had similar risk for dyslipidaemia and
      hypertension as those never obese or overweight (all RRs close to 1). However,
      they had significantly higher risk for increased cIMT (RR = 3.37, 95% CI = 1.80
      6.39). Conclusion: The long-term BMI trajectories that reach or persist at high
      levels associate with CVD risk factors in adulthood. Stabilizing BMI in obese
      adults and resolving elevated child BMI by adulthood might limit and reduce
      adverse cardiometabolic profiles. However, efforts to prevent child obesity might
      be most effective to reduce the risk for adult atherosclerosis.

PMID- 29635284
TI  - Divergent Role of Estrogen-Related Receptor alpha in Lipid- and Fasting-Induced
      Hepatic Steatosis in Mice.
AB  - Given the increasing prevalence of obesity and the metabolic syndrome,
      identification of intrinsic molecular programs responsible for ensuring fuel
      homeostasis and preventing metabolic disease is needed. We investigated whether
      the orphan nuclear receptor estrogen-related receptor alpha (ERRalpha), a major
      regulator of energy metabolism, plays a role in lipid homeostasis and the
      development of nonalcoholic fatty liver disease (NAFLD) in response to chronic
      high-fat diet (HFD) consumption and long-term fasting. Systemic ablation of
      ERRalpha in mice demonstrated clear beneficial effects for loss of ERRalpha
      function in protection from HFD-provoked body weight gain manifested not only
      from a reduction in white adipose tissue stores but also from an impediment in
      intrahepatic lipid accumulation. The prevention of HFD-induced NAFLD in ERRalpha
      null mice was underscored by transcriptional repression of de novo lipogenesis,
      which was upregulated in wild-type mice, a known contributing factor to lipid
      stimulated hepatic steatosis. Surprisingly, given these findings, ERRalpha
      deficiency had no significant impact on the degree of fasting-induced NAFLD,
      involving the mobilization of adipocyte triglyceride (TG) stores into the liver.
      However, the presence of ERRalpha was essential for acute refeeding-mediated
      reversal of fasting-induced hepatic TG accretion, underpinned by impaired
      downregulation of adipose TG lipolysis and reduced hepatic mitochondrial
      oxidative activity. Taken together, the regulation of lipid handling by ERRalpha
      depended on the nutritional state, suggesting that negative modulation of
      ERRalpha activity could be envisaged to prevent lipid-induced NAFLD, whereas
      inducing its activity would be useful to treat and reverse the instilled disease.

PMID- 29635285
TI  - Chronic Medical Conditions and Peripartum Mental Illness: A Systematic Review and
      Meta-Analysis.
AB  - The objective of this systematic review and meta-analysis was to examine the
      association between maternal chronic medical conditions (CMCs) and peripartum
      mental illness. MEDLINE, Embase, CINAHL, and PsycINFO were searched to September
      2017. Data were extracted and quality was assessed using standardized
      instruments. We generated unadjusted and adjusted pooled odds ratios and 95%
      confidence intervals using DerSimonian and Laird random effects models. The
      review included 16 papers representing 12 studies and 1,626,260 women. CMCs
      overall were associated with peripartum mental illness overall (adjusted pooled
      odds ratios (aPOR) = 1.43, 95% confidence interval (CI): 1.25, 1.63). CMCs
      overall were associated with antepartum (aPOR = 1.41, 95% CI: 1.10, 1.81) and
      postpartum mental illness separately (aPOR = 1.44, 95% CI: 1.13, 1.85) and with
      peripartum depression (aPOR = 1.45, 95% CI: 1.25, 1.67) and anxiety separately
      (aPOR = 1.63, 95% CI: 1.35, 1.95). No studies examined bipolar or psychotic
      disorders. Diabetes (aPOR = 1.34, 95% CI: 1.07, 1.69), hypertension/heart disease
      (aPOR = 1.60, 95% CI: 1.05, 2.45), migraine (aPOR = 1.75, 95% CI: 1.20, 2.54),
      and other neurological disorders (aPOR = 1.45, 95% CI: 1.19, 1.77), but not
      asthma, were each associated with peripartum mental illness. Findings suggest
      that mental health resources should be integrated in medical settings where
      pregnant and postpartum women with CMCs are treated.

PMID- 29635286
TI  - Preliminary Efficacy Testing of the Disinfectant MicrobeCare XLP for Potential
      Use in Military Operational Environments.
AB  - Introduction: A safe, easy-to-use, permanently bonded antiseptic that does not
      require post-exposure bioload reduction but maintains effectiveness over time
      would have far-reaching implications across multiple industries. Health care is
      one such arena, particularly in austere military settings where resources are at
      a premium. MicrobeCare XLP (MicrobeCare, Buffalo Grove, IL, USA) is a
      commercially available spray-on agent that is advertised to covalently bond to
      surfaces and provide a long-lasting antimicrobial coating inhospitable to >99.99%
      of surface microorganisms. A pilot study was devised to gather baseline data
      regarding product efficacy and laboratory parameters before consideration of
      extended investigations and military utilization. The product manufacturer
      recommends bioload reductions before product application, following product
      application, and after each pathogenic exposure. To investigate the product's
      efficacy in circumstances more closely simulating a military operational setting
      in which post-pathogenic exposure bioload reduction would not be possible, this
      step was deliberately excluded from the test sequences. Materials and Methods:
      Using autoclaved surgical forceps, growth of Staphylococcus aureus and
      Acinetobacter baumannii was evaluated in a controlled manner under multiple
      conditions. Test variations included duration of submersion in the MicrobeCare
      XLP solution and air-drying and a second autoclave sterilization. Control and
      treated forceps were exposed to a bacterial suspension and air-dried before being
      submerged in sterile saline and vortex mixed. The saline solution was serially
      diluted and plated on tryptic soy agar (TSA) II plates. Plates were incubated for
      24 h and bacterial colony-forming units (CFU)/mL were counted. Results:
      Statistical significance was defined according to the American Society for
      Testing and Materials (ASTM) International passing criteria of 3 Log10 or 99.9%
      reduction of microorganisms. Additionally, p-values were calculated using two
      tailed unpaired two-sample t-tests with unequal variance with a threshold of
      0.05. In the S. aureus tests, none of the reduction calculations met the ASTM
      International passing criteria. In addition, the difference between the means of
      the colony counts in the MicrobeCare XLP-treated forceps and untreated control
      forceps was not statistically significant (p-value 0.109). Conversely, in the A.
      baumannii tests, each of the percent reduction calculations met the ASTM
      International passing criteria; the difference between the means of the colony
      counts in the treatment and control groups was statistically significant (p-value
      0.008). Conclusion: In these independent tests, MicrobeCare XLP effectively
      prevented growth of A. baumannii but had unpredictable results suppressing S.
      aureus. These results may relate to inherent properties of the bacteria or
      autoclave exposure, although the manufacturer asserts that the coating withstands
      such degradation. Additional testing could be performed using a broader range of
      microorganisms and exposure to varying conditions including other sterilization
      methods.

PMID- 29635287
TI  - The draft genome sequence of forest musk deer (Moschus berezovskii).
AB  - Background: The forest musk deer, Moschus berezovskii, is one of seven musk deer
      (Moschus spp.) and is distributed in Southwest China. Akin to other musk deer,
      the forest musk deer has been traditionally and is currently hunted for its musk
      (i.e., global perfume industry). Considerable hunting pressure and habitat loss
      have caused significant population declines. Consequently, the Chinese government
      commenced captive breeding programs for musk harvesting in the 1950s. However,
      the prevalence of fatal diseases is considerably restricting population
      increases. Disease severity and extent are exacerbated by inbreeding and genetic
      diversity declines in captive musk deer populations. It is essential that
      knowledge of captive and wild forest musk deer populations' immune system and
      genome be gained in order to improve their physical and genetic health. We have
      thus sequenced the whole genome of the forest musk deer, completed the genomic
      assembly and annotation, and performed preliminary bioinformatic analyses.
      Findings: A total of 407 Gb raw reads from whole-genome sequencing were generated
      using the Illumina HiSeq 4000 platform. The final genome assembly is around 2.72
      Gb, with a contig N50 length of 22.6 kb and a scaffold N50 length of 2.85 Mb. We
      identified 24,352 genes and found that 42.05% of the genome is composed of
      repetitive elements. We also detected 1,236 olfactory receptor genes. The genome
      wide phylogenetic tree indicated that the forest musk deer was within the order
      Artiodactyla, and it appeared as the sister clade of four members of Bovidae. In
      total, 576 genes were under positive selection in the forest musk deer lineage.
      Conclusions: We provide the first genome sequence and gene annotation for the
      forest musk deer. The availability of these resources will be very useful for the
      conservation and captive breeding of this endangered and economically important
      species and for reconstructing the evolutionary history of the order
      Artiodactyla.

PMID- 29635289
TI  - Re: Spinal Cord Stimulation (SCS) with Anatomically Guided (3D) Neural Targeting
      Shows Superior Chronic Axial Low Back Pain Relief Compared to Traditional SCS
      LUMINA Study.

PMID- 29635288
TI  - Maternal diet-induced obesity programmes cardiac dysfunction in male mice
      independently of post-weaning diet.
AB  - Aims: Obesity during pregnancy increases risk of cardiovascular disease (CVD) in
      the offspring and individuals exposed to over-nutrition during fetal life are
      likely to be exposed to a calorie-rich environment postnatally. Here, we
      established the consequences of combined exposure to a maternal and post-weaning
      obesogenic diet on offspring cardiac structure and function using an established
      mouse model of maternal diet-induced obesity. Methods and results: The impact of
      the maternal and postnatal environment on the offspring metabolic profile,
      arterial blood pressure, cardiac structure, and function was assessed in 8-week
      old C57BL/6 male mice. Measurement of cardiomyocyte cell area, the
      transcriptional re-activation of cardiac fetal genes as well as genes involved in
      the regulation of contractile function and matrix remodelling in the adult heart
      were determined as potential mediators of effects on cardiac function. In the
      adult offspring: a post-weaning obesogenic diet coupled with exposure to maternal
      obesity increased serum insulin (P < 0.0001) and leptin levels (P < 0.0001);
      maternal obesity (P = 0.001) and a post-weaning obesogenic diet (P = 0.002)
      increased absolute heart weight; maternal obesity (P = 0.01) and offspring
      obesity (P = 0.01) caused cardiac dysfunction but effects were not additive;
      cardiac dysfunction resulting from maternal obesity was associated with re
      expression of cardiac fetal genes (Myh7: Myh6 ratio; P = 0.0004), however, these
      genes were not affected by offspring diet; maternal obesity (P = 0.02); and
      offspring obesity (P = 0.05) caused hypertension and effects were additive.
      Conclusions: Maternal diet-induced obesity and offspring obesity independently
      promote cardiac dysfunction and hypertension in adult male progeny. Exposure to
      maternal obesity alone programmed cardiac dysfunction, associated with hallmarks
      of pathological left ventricular hypertrophy, including increased cardiomyocyte
      area, upregulation of fetal genes, and remodelling of cardiac structure. These
      data highlight that the perinatal period is just as important as adult-onset
      obesity in predicting CVD risk. Therefore, early developmental periods are key
      intervention windows to reduce the prevalence of CVD.

PMID- 29635290
TI  - Appropriateness of magnetic resonance imaging requested by primary care
      physicians for patients with knee pain.
AB  - Objective: To evaluate the appropriateness of magnetic resonance imaging (MRI) of
      the knee requested by primary care physicians. Design: Retrospective
      observational study. Setting: Six primary care centres in the Elche Department of
      Health of the Valencian Community, Spain. Participants: Three hundred patients
      with knee pain who were prescribed MRI. Main Outcome Measures: Data were
      collected from the electronic clinical history, which allowed us to assess the
      appropriateness and inappropriateness of the MRI requests for the knee based on
      the American College of Radiology (ACR) criteria. A multivariate logistic
      regression model was used to identify factors associated with an inappropriate
      request. Results: About 45% (41-49%) of knee MRI prescriptions were assessed as
      inappropriate. The frequency was higher in female patients (odds ratio, OR =
      1.96; P = 0.03). A history of knee trauma and urgent use of MRI were associated
      with a lower frequency of inappropriate requests (OR = 0.14, P < 0.001 and OR =
      0.32, P = 0.03, respectively). In 82% of cases, the request for MRI was deemed
      inappropriate because it was used as the initial imaging test. The availability
      of a previous radiograph of the knee significantly reduced the rate of
      inappropriate requests (OR = 0.05, P < 0.001); only 47% of the patients had a
      previous radiograph. Conclusions: The percentage of inappropriate knee MRI
      prescriptions is high. Protocols should be put in place to improve the
      appropriateness of MRI requests by promoting understanding of the appropriate use
      of MRI among primary care physicians.

PMID- 29635291
TI  - Increased Circulating FGF23 Does Not Lead to Cardiac Hypertrophy in the Male Hyp
      Mouse Model of XLH.
AB  - Serum levels of fibroblast growth factor 23 (FGF23) markedly increase with renal
      impairment, with FGF23 levels correlating with the presence of left ventricular
      hypertrophy (LVH) and mortality in patients with chronic kidney disease (CKD).
      FGF23 activates calcineurin/nuclear factor of activated T cell (NFAT) signaling
      and induces hypertrophy in murine cardiomyocytes. X-linked hypophosphatemia (XLH)
      is characterized by high circulating levels of FGF23 but, in contrast to CKD, is
      associated with hypophosphatemia. The cardiac effects of high circulating levels
      of FGF23 in XLH are not well defined. Thus, studies were undertaken to define the
      cardiac phenotype in the mouse model of XLH (Hyp mice). Echocardiographic and
      histological analyses demonstrated that Hyp left ventricles (LVs) are smaller
      than those of wild-type mice. Messenger RNA expression of cardiac hypertrophy
      markers was not altered in the LV or right ventricle of Hyp mice. However, the
      Hyp LVs had increased expression of the NFAT target genes NFATc1 and RCAN1. To
      determine whether phosphate alone can induce markers of hypertrophy,
      differentiated C2C12 myocytes were treated with phosphate. Phosphate treatment
      increased expression of cardiac hypertrophy markers, supporting a primary role
      for phosphate in inducing LVH. Although previous studies showed that increased
      circulating FGF23 and phosphate levels are associated with LVH, our results
      demonstrated that in XLH, high circulating levels of FGF23 in the setting of
      hypophosphatemia do not induce cardiac hypertrophy.

PMID- 29635293
TI  - Effects of Moth Age and Rearing Temperature on the Flight Performance of the
      Loreyi Leafworm, Mythimna loreyi (Lepidoptera: Noctuidae), in Tethered and Free
      Flight.
AB  - To understand the migratory flight behaviors of the loreyi leafworm, Mythimna
      loreyi Walker (Lepidoptera: Noctuidae), both tethered (flight distance, time, and
      velocity) and free-flight activity (flight action, duration, and frequency) of
      adults at different ages, sexes, and temperatures were investigated using
      computer-controlled insect flight mills and an autonomous flight monitoring
      system. Tethered flight activity differed significantly among ages and rearing
      temperature, but not sex. Newly emerged adults (the first day after emergence)
      displayed the lowest flight time, distance, and speed. However, flight
      performance increased with age, peaking at 3 d. Relatively strong flight
      performance was maintained up to 5 d postemergence and then declined
      significantly by day 6. There was no significant difference in flight performance
      between sexes for 3-d-old moths. Adults reared as larvae at 24 degrees C averaged
      significantly longer flight duration and distance than those reared at other
      temperatures. Both lower and higher rearing temperatures negatively affected
      tethered flight. Similar results among age and rearing temperature treatments
      were observed in autonomous free-flight tests. During 12-h free-flight tests,
      flight activity peaked from 6 to 10 h after beginning of darkness. Free-flight
      activity of 1- and 6-d-old adults was significantly less than that of 3-, 4-, and
      5-d-old adults. Adults reared at 24 degrees C showed significantly greater free
      flight action, duration, and frequency than those reared at other temperatures.
      The results suggest that M. loreyi may be a migratory species.

PMID- 29635292
TI  - Comparative whole genome DNA methylation profiling of cattle sperm and somatic
      tissues reveals striking hypomethylated patterns in sperm.
AB  - Background: Although sperm DNA methylation has been studied in humans and other
      species, its status in cattle is largely unknown. Results: Using whole-genome
      bisulfite sequencing (WGBS), we profiled the DNA methylome of cattle sperm
      through comparison with three somatic tissues (mammary gland, brain, and blood).
      Large differences between cattle sperm and somatic cells were observed in the
      methylation patterns of global CpGs, pericentromeric satellites, partially
      methylated domains (PMDs), hypomethylated regions (HMRs), and common repeats. As
      expected, we observed low methylation in the promoter regions and high
      methylation in the bodies of active genes. We detected selective hypomethylation
      of megabase domains of centromeric satellite clusters, which may be related to
      chromosome segregation during meiosis and their rapid transcriptional activation
      upon fertilization. We found more PMDs in sperm cells than in somatic cells and
      identified meiosis-related genes such asKIF2B and REPIN1, which are
      hypomethylated in sperm but hypermethylated in somatic cells. In addition to the
      common HMRs around gene promoters, which showed substantial differences between
      sperm and somatic cells, the sperm-specific HMRs also targeted to distinct
      spermatogenesis-related genes, including BOLL, MAEL, ASZ1, SYCP3, CTCFL, MND1,
      SPATA22, PLD6, DDX4, RBBP8, FKBP6, and SYCE1. Although common repeats were
      heavily methylated in both sperm and somatic cells, some young Bov-A2 repeats,
      which belong to the SINE family, were hypomethylated in sperm and could affect
      the promoter structures by introducing new regulatory elements. Conclusions: Our
      study provides a comprehensive resource for bovine sperm epigenomic research and
      enables new discoveries about DNA methylation and its role in male fertility.

PMID- 29635294
TI  - Criteria for evaluating programme theory diagrams in quality improvement
      initiatives: a structured method for appraisal.
AB  - Background: Despite criticisms that many quality improvement (QI) initiatives
      fail due to incomplete programme theory, there is no defined way to evaluate how
      programme theory has been articulated. The objective of this research was to
      develop, and assess the usability and reliability of scoring criteria to evaluate
      programme theory diagrams. Methods: Criteria development was informed by
      published literature and QI experts. Inter-rater reliability was tested between
      two evaluators. About 63 programme theory diagrams (42 driver diagrams and 21
      action-effect diagrams) were reviewed to establish whether the criteria could
      support comparative analysis of different approaches to constructing diagrams.
      Results: Components of the scoring criteria include: assessment of overall aim,
      logical overview, clarity of components, cause-effect relationships, evidence and
      measurement. Independent reviewers had 78% inter-rater reliability. Scoring
      enabled direct comparison of different approaches to developing programme theory;
      action-effect diagrams were found to have had a statistically significant but
      moderate improvement in programme theory quality over driver diagrams; no
      significant differences were observed based on the setting in which driver
      diagrams were developed. Conclusions: The scoring criteria summarise the
      necessary components of programme theory that are thought to contribute to
      successful QI projects. The viability of the scoring criteria for practical
      application was demonstrated. Future uses include assessment of individual
      programme theory diagrams and comparison of different approaches (e.g.
      methodological, teaching or other QI support) to produce programme theory. The
      criteria can be used as a tool to guide the production of better programme theory
      diagrams, and also highlights where additional support for QI teams could be
      needed.

PMID- 29635295
TI  - The Emergence and Development of Bioethics in the Uk.
AB  - Bioethics emerged in a specific social and historical context. Its relationship
      to older traditions in medical ethics and to environmental ethics is an ongoing
      matter of debate. This article analyses the social, institutional, and economic
      factors that led to the development of bioethics in the UK in the 1980s, and the
      course it has taken since. We show how phenomena such as globalisation, the focus
      on 'ethical legal and social issues' and the empirical turn have affected the
      methods employed, and argue that ongoing controversies about the nature and
      possibility of ethical expertise will affect its future.

PMID- 29635296
TI  - Piggy: a rapid, large-scale pan-genome analysis tool for intergenic regions in
      bacteria.
AB  - Background: The concept of the "pan-genome," which refers to the total complement
      of genes within a given sample or species, is well established in bacterial
      genomics. Rapid and scalable pipelines are available for managing and
      interpreting pan-genomes from large batches of annotated assemblies. However,
      despite overwhelming evidence that variation in intergenic regions in bacteria
      can directly influence phenotypes, most current approaches for analyzing pan
      genomes focus exclusively on protein-coding sequences. Findings: To address this
      we present Piggy, a novel pipeline that emulates Roary except that it is based
      only on intergenic regions. A key utility provided by Piggy is the detection of
      highly divergent ("switched") intergenic regions (IGRs) upstream of genes. We
      demonstrate the use of Piggy on large datasets of clinically important lineages
      of Staphylococcus aureus and Escherichia coli. Conclusions: For S. aureus, we
      show that highly divergent (switched) IGRs are associated with differences in
      gene expression and we establish a multilocus reference database of IGR alleles
      (igMLST; implemented in BIGSdb).

PMID- 29635298
TI  - A micro X-ray computed tomography dataset of South African hermit crabs
      (Crustacea: Decapoda: Anomura: Paguroidea) containing scans of two rare specimens
      and three recently described species.
AB  - Background: Along with the conventional deposition of physical types at natural
      history museums, the deposition of 3-dimensional (3D) image data has been
      proposed for rare and valuable museum specimens, such as irreplaceable type
      material. Findings: Micro computed tomography (MUCT) scan data of 5 hermit crab
      species from South Africa, including rare specimens and type material, depicted
      main identification characteristics of calcified body parts. However, low-image
      contrasts, especially in larger (>50 mm total length) specimens, did not allow
      sufficient 3D reconstructions of weakly calcified and fine characteristics, such
      as soft tissue of the pleon, mouthparts, gills, and setation. Reconstructions of
      soft tissue were sometimes possible, depending on individual sample and scanning
      characteristics. The raw data of seven scans are publicly available for download
      from the GigaDB repository. Conclusions: Calcified body parts visualized from
      MUCT data can aid taxonomic validation and provide additional, virtual deposition
      of rare specimens. The use of a nondestructive, nonstaining MUCT approach for
      taxonomy, reconstructions of soft tissue structures, microscopic spines, and
      setae depend on species characteristics. Constrained to these limitations, the
      presented dataset can be used for future morphological studies. However, our
      virtual specimens will be most valuable to taxonomists who can download a digital
      avatar for 3D examination. Simultaneously, in the event of physical damage to or
      loss of the original physical specimen, this dataset serves as a vital insurance
      policy.

PMID- 29635297
TI  - Genome Annotation Generator: a simple tool for generating and correcting WGS
      annotation tables for NCBI submission.
AB  - Background: One of the most overlooked, yet critical, components of a whole
      genome sequencing (WGS) project is the submission and curation of the data to a
      genomic repository, most commonly the National Center for Biotechnology
      Information (NCBI). While large genome centers or genome groups have developed
      software tools for post-annotation assembly filtering, annotation, and conversion
      into the NCBI's annotation table format, these tools typically require back-end
      setup and connection to an Structured Query Language (SQL) database and/or some
      knowledge of programming (Perl, Python) to implement. With WGS becoming
      commonplace, genome sequencing projects are moving away from the genome centers
      and into the ecology or biology lab, where fewer resources are present to support
      the process of genome assembly curation. To fill this gap, we developed software
      to assess, filter, and transfer annotation and convert a draft genome assembly
      and annotation set into the NCBI annotation table (.tbl) format, facilitating
      submission to the NCBI Genome Assembly database. This software has no
      dependencies, is compatible across platforms, and utilizes a simple command to
      perform a variety of simple and complex post-analysis, pre-NCBI submission WGS
      project tasks. Findings: The Genome Annotation Generator is a consistent and user
      friendly bioinformatics tool that can be used to generate a .tbl file that is
      consistent with the NCBI submission pipeline. Conclusions: The Genome Annotation
      Generator achieves the goal of providing a publicly available tool that will
      facilitate the submission of annotated genome assemblies to the NCBI. It is
      useful for any individual researcher or research group that wishes to submit a
      genome assembly of their study system to the NCBI.

PMID- 29635299
TI  - Evaluation of Alternatives to an Organophosphate Insecticide with Selected
      Cultural Practices: Effects on Thrips, Frankliniella fusca, and Incidence of
      Spotted Wilt in Peanut Farmscapes.
AB  - Peanut growers use a combination of tactics to manage spotted wilt disease caused
      by thrips-transmitted Tomato spotted wilt virus (TSWV). They include planting
      TSWV-resistant cultivars, application of insecticides, and various cultural
      practices. Two commonly used insecticides against thrips are aldicarb and
      phorate. Both insecticides exhibit broad-spectrum toxicity. Recent research has
      led to the identification of potential alternatives to aldicarb and phorate. In
      this study, along with reduced-risk, alternative insecticides, we evaluated the
      effect of conventional versus strip tillage; single versus twin row seeding
      pattern; and 13 seed/m versus 20 seed/m on thips density, feeding injury, and
      spotted wilt incidence. Three field trials were conducted in Georgia in 2012 and
      2013. Thrips counts, thrips feeding injuriy, and incidence of spotted wilt were
      less under strip tillage than under conventional tillage. Reduced feeding injury
      from thrips was observed on twin-row plots compared with single-row plots. Thrips
      counts, thrips feeding injury, and incidence of spotted wilt did not vary by
      seeding rate. Yield from twin-row plots was greater than yield from single-row
      plots only in 2012. Yield was not affected by other cultural practices.
      Alternative insecticides, including imidacloprid and spinetoram, were as
      effective as phorate in suppressing thrips and reducing incidence of spotted wilt
      in conjunction with cultural practices. Results suggest that cultural practices
      and reduced-risk insecticides (alternatives to aldicarb and phorate) can
      effectively suppress thrips and incidence of spotted wilt in peanut.

PMID- 29635301
TI  - Review of VA Clinical Guidance for the Health Conditions Identified by the Camp
      Lejeune Legislation.

PMID- 29635300
TI  - Folate Receptor Near-Infrared Optical Imaging Provides Sensitive and Specific
      Intraoperative Visualization of Nonfunctional Pituitary Adenomas.
AB  - BACKGROUND: Surgical resection is the primary treatment for nonfunctional (NF)
      pituitary adenomas, but gross-total resection is difficult to achieve in all
      cases. NF adenomas overexpress folate receptor alpha (FRalpha). OBJECTIVE: To
      test the hypothesis that we could target FRalpha for highly sensitive and
      specific intraoperative detection of NF adenomas using near-infrared (NIR)
      imaging. METHODS: Fourteen patients with NF pituitary adenoma were infused with
      the folate analog NIR dye OTL38 preoperatively. NIR fluorescence signal-to
      background ratio (SBR) was recorded for each tumor during resection of the
      adenomas. Extent of surgery was not modified based on the presence or absence of
      fluorescence. Immunohistochemistry was performed to assess FRalpha expression in
      all specimens. Magnetic resonance imaging (MRI) was performed postoperatively to
      assess residual neoplasm. RESULTS: Nine adenomas overexpressed FRalpha and
      fluoresced with a NIR SBR of 3.2 +/- 0.52, whereas the 5 non-FRalpha
      overexpressing adenomas fluoresced with an SBR of 1.5 +/- 0.21. Linear regression
      demonstrated a significant correlation between intraoperative SBR and the FRalpha
      expression (P-value < .001). Analysis of 14 margin samples revealed that the
      surgeon's impression of the tissue had 83% sensitivity, 100% specificity, 100%
      positive predictive value, and 89% negative predictive value, while NIR
      fluorescence had 100% for all values. NIR fluorescence accurately predicted
      postoperative MRI results in 78% of FRalpha-overexpressing patients. CONCLUSION:
      Preoperative injection of folate-tagged NIR dye provides strong signal and
      visualization of NF pituitary adenomas. It is 100% sensitive and specific for
      detecting margin neoplasm and can predict postoperative MRI findings. Our results
      suggest that NIR fluorescence may be superior to white-light visualization alone
      and may improve resection rates in NF pituitary adenomas.

PMID- 29635302
TI  - Microsurgical Resection of Medulla Oblongata Hemangioblastoma: 2-Dimensional
      Operative Video.
AB  - This video demonstrates the microsurgical resection of brainstem
      hemangioblastoma. The patient is a 32-yr-old woman with Von Hippel Lindau
      syndrome who presented with quadriparesis and inability to swallow. Magnetic
      resonance imaging (MRI) of the neuroaxis revealed a brainstem cystic lesion with
      contrast-enhancing tumor nodule right along the posterior aspect of the lower
      part of medulla oblongata. The surgery was performed in the prone position with
      suboccipital craniectomy and partial C1 posterior arch removal. The aim of the
      surgery was to remove the tumor nodule.1-12The tumor was separated from the right
      dorsal nerve roots, and then progressively dissected with coagulation of arterial
      feeders and draining vein and division of the pia circumferentially.
      Postoperative MRI revealed complete resection. The patient completely recovered
      from her quadriparesis and difficulty swallowing.

PMID- 29635303
TI  - The Effectiveness of Mindfulness- and Acceptance-Based Interventions for Informal
      Caregivers of People With Dementia: A Meta-Analysis.
AB  - Background and Objectives: The application of mindfulness- and acceptance-based
      interventions (MABIs) for informal caregivers of people with dementia (PwD) is
      relatively novel, and the current state of the evidence base is unclear. This
      meta-analysis examined the effectiveness of MABIs on reducing symptoms of
      depression and burden in informal caregivers of PwD. The quality of included
      studies was evaluated and moderator variables explored. Research Design and
      Methods: A literature search of six electronic databases (PsycARTICLES, PsycINFO,
      MEDLINE Complete, SCOPUS, Web of Science, and ProQuest) was conducted from the
      first available date to 20 December 2016. Inclusion criteria involved studies
      that quantitatively investigated the impact of MABIs on depression and/or burden
      in informal caregivers of PwD. Results: Twelve studies, providing data on 321
      caregivers, were included. Most used mindfulness-based stress reduction and were
      conducted in the United States. The average attrition among participants was
      15.83%. The pre-post effect of MABIs was large for depression and moderate for
      burden. These effects were largely maintained at follow-up. Significant
      heterogeneity of effect sizes was observed, with no significant moderators
      identified. Study quality varied from very poor to moderately good. Discussion
      and Implications: The low attrition and moderate to large effects suggest that
      MABIs are acceptable and beneficial for informal caregivers of PwD. The lack of
      significant moderators could advocate services using more cost-effective forms of
      MABIs. Further higher-quality research is needed to improve the robustness of the
      evidence base and enable a meta-analysis to thoroughly examine and quantify
      moderator variables.

PMID- 29635304
TI  - Electronic checklists improve referral letters in gastroenterology: a randomized
      vignette survey.
AB  - Objective: Investigate whether gastroenterologists rate the quality of referral
      letters higher if electronic dynamic checklist items are added to a standard free
      text referral letter. Assess how this affects the gastroenterologists' assessment
      of the patient's need for healthcare and the agreement between their assessments.
      Design: Randomized vignette study. Setting: Norwegian primary gastroenterology
      services. Participants: Thirty-two Norwegian gastroenterologists. Intervention:
      Between June 2015 and January 2016, participants were recruited through an open
      invitation to all members of the Norwegian Society of Gastroenterology. They were
      asked to rate 16 referral letters (vignettes) in a web interface: eight letters
      in free text following a general template and eight letters based on a general
      referral template combined with diagnosis-specific checklist items. The study was
      completed in two subsequent rounds >=3 months apart. Main Outcome Measures:
      Quality of referral letters assessed on a rating scale from 0 to 10. Agreement in
      the referral assessment and accuracy of the selection of correct preliminary
      diagnosis and appropriate work-up. Results: The mean quality assesses on the
      rating scale was 7.0 (95% confidence interval [CI] 6.8-7.2) for all letters
      combined (n = 511), 6.5(CI 6.2-6.8) for the free-text referrals (n = 256) and
      7.5(CI 7.3-7.7) for the checklist referrals (n = 255) (P < 0.001, paired t-test).
      No difference was observed in the triage of the patients, but fewer
      gastroenterologists felt the need to collect additional information about the
      patients in the checklist group. Conclusion: Checklist items may ease the
      assessment of the referrals for gastroenterologists. We were not able to show
      that checklists significantly influence the management of patients.

PMID- 29635305
TI  - Modeling the Western Diet for Preclinical Investigations.
AB  - Rodent models have been invaluable for biomedical research. Preclinical
      investigations with rodents allow researchers to investigate diseases by using
      study designs that are not suitable for human subjects. The primary criticism of
      preclinical animal models is that results are not always translatable to humans.
      Some of this lack of translation is due to inherent differences between species.
      However, rodent models have been refined over time, and translatability to humans
      has improved. Transgenic animals have greatly aided our understanding of
      interactions between genes and disease and have narrowed the translation gap
      between humans and model animals. Despite the technological innovations of animal
      models through advances in genetics, relatively little attention has been given
      to animal diets. Namely, developing diets that replicate what humans eat will
      help make animal models more relevant to human populations. This review focuses
      on commonly used rodent diets that are used to emulate the Western dietary
      pattern in preclinical studies of obesity and type 2 diabetes, nonalcoholic liver
      disease, maternal nutrition, and colorectal cancer.

PMID- 29635307
TI  - It Takes Two to Read: Interactive Reading with Young Deaf and Hard-of-Hearing
      Children.
AB  - Interactive storybook reading is an important activity to enhance the emergent
      literacy skills of young deaf and hard-of-hearing (DHH) children. Parents have a
      crucial role to play in promoting their children's literacy development. However,
      parents often do not read in an interactive way; therefore guidance is
      recommended in applying these interactive reading strategies. In the present
      study we examined how parent reading behavior was affected by implementing an
      interactive reading training program for parents of young DHH children. Parents
      of 18 DHH toddlers in the Netherlands participated in a series of group training
      sessions and their interactive reading behavior was compared to that of 10
      parents who did not participate. The results showed that parents' interactive
      reading behavior tended to increase after they participated in the interactive
      reading program. After the program, they applied the interactive reading
      strategies more often than parents who had not participated in the program. The
      findings suggest that interactive reading programs should be incorporated into
      early intervention programs for DHH children.

PMID- 29635308
TI  - Target-based selectivity of strigolactone agonists and antagonists in plants and
      their potential use in agriculture.
AB  - Strigolactones (SLs) are small carotenoid-derived molecules that possess a wide
      spectrum of functions, including plant hormonal activities and chemical mediation
      of rhizosphere communication with both root parasitic plants and symbiotic
      arbuscular mycorrhizal fungi. Chemicals that regulate the functions of SLs may
      therefore have the potential to become widely used in agricultural applications.
      For example, various SL analogs and mimics have been developed to reduce the seed
      banks of root parasites in the field. Other analogs and mimics act selectively to
      suppress branching, with weak, or no stimulation, of germination in root
      parasites. In addition, some antagonists for SL receptors have been developed
      based on the mechanisms of SL perception. A better understanding of the modes of
      action of SL perception by various receptors will help to support the design of
      SL analogs, mimics, and antagonists with high activity and selectivity. Here, we
      review the compounds reported so far from the viewpoint of their selectivity to
      their targets, and the possibilities for their use in agriculture.

PMID- 29635306
TI  - Pleiotropic mapping and annotation selection in genome-wide association studies
      with penalized Gaussian mixture models.
AB  - Motivation: Genome-wide association studies (GWASs) have identified many genetic
      loci associated with complex traits. A substantial fraction of these identified
      loci is associated with multiple traits-a phenomena known as pleiotropy.
      Identification of pleiotropic associations can help characterize the genetic
      relationship among complex traits and can facilitate our understanding of disease
      etiology. Effective pleiotropic association mapping requires the development of
      statistical methods that can jointly model multiple traits with genome-wide
      single nucleic polymorphisms (SNPs) together. Results: We develop a joint
      modeling method, which we refer to as the integrative MApping of Pleiotropic
      association (iMAP). iMAP models summary statistics from GWASs, uses a
      multivariate Gaussian distribution to account for phenotypic correlation,
      simultaneously infers genome-wide SNP association pattern using mixture modeling
      and has the potential to reveal causal relationship between traits. Importantly,
      iMAP integrates a large number of SNP functional annotations to substantially
      improve association mapping power, and, with a sparsity-inducing penalty, is
      capable of selecting informative annotations from a large, potentially non
      informative set. To enable scalable inference of iMAP to association studies with
      hundreds of thousands of individuals and millions of SNPs, we develop an
      efficient expectation maximization algorithm based on an approximate penalized
      regression algorithm. With simulations and comparisons to existing methods, we
      illustrate the benefits of iMAP in terms of both high association mapping power
      and accurate estimation of genome-wide SNP association patterns. Finally, we
      apply iMAP to perform a joint analysis of 48 traits from 31 GWAS consortia
      together with 40 tissue-specific SNP annotations generated from the Roadmap
      Project. Availability and implementation: iMAP is freely available at
      http://www.xzlab.org/software.html. Supplementary information: Supplementary data
      are available at Bioinformatics online.

PMID- 29635309
TI  - The Neuropsychological Profile and Phenomenology of Late Onset Psychosis: A Cross
      sectional Study on the Differential Diagnosis of Very-Late-Onset Schizophrenia
      Like Psychosis, Dementia with Lewy Bodies and Alzheimer's Type Dementia with
      Psychosis.
AB  - Objective: Late onset psychosis not only occurs as a prodromal symptom to
      neurodegeneration, but it can also be associated with a non-progressive mild
      cognitive deficit. Studying the phenomenology of psychotic symptoms and the
      neuropsychological profile may serve as sensitive and non-invasive tools for
      differential diagnosis. Method: We compared 57 individuals with very-late-onset
      schizophrenia-like psychosis (VLOSLP), 49 participants with Dementia with Lewy
      Bodies (DLB) and 35 patients with Alzheimer's type Dementia and psychosis (AD+P)
      concerning the phenomenology of psychotic symptoms and the neuropsychological
      profile using several measures of cognitive function in a cross-sectional study.
      Results: Participants with DLB exhibited more visual hallucinations, especially
      those involving animals, and less partition/paranoid delusions than both other
      groups. VLOSLP showed more partition delusions and auditory hallucinations of
      human voices than both other groups. Hence, patients with DLB and VLOSLP showed
      greater dissimilarity in the phenomenology of psychosis, whereas individuals with
      AD+P held an intermediate position. Processing speed and executive function were
      comparably impaired among the three groups, as was expected considering a common
      underlying set of neurobiological abnormalities for psychosis. However, AD+P
      showed more strongly reduced learning and consolidation skills, whereas DLB was
      associated with prominent visuoconstructive deficits. Conclusions: Phenomenology
      of psychosis may prove especially informative when comparing individuals with DLB
      to those with VLOSLP. Neuropsychological profiles are able to further aid
      differential diagnosis of the three groups.

PMID- 29635310
TI  - 3DClusterViSu: 3D clustering analysis of super-resolution microscopy data by 3D
      Voronoi tessellations.
AB  - Motivation: Single-molecule localization microscopy (SMLM) can play an important
      role in integrated structural biology approaches to identify, localize and
      determine the 3D structure of cellular structures. While many tools exist for the
      3D analysis and visualization of crystal or cryo-EM structures little exists for
      3D SMLM data, which can provide unique insights but are particularly challenging
      to analyze in three dimensions especially in a dense cellular context. Results:
      We developed 3DClusterViSu, a method based on 3D Voronoi tessellations that
      allows local density estimation, segmentation and quantification of 3D SMLM data
      and visualization of protein clusters within a 3D tool. We show its robust
      performance on microtubules and histone proteins H2B and CENP-A with distinct
      spatial distributions. 3DClusterViSu will favor multi-scale and multi-resolution
      synergies to allow integrating molecular and cellular levels in the analysis of
      macromolecular complexes. Availability and impementation: 3DClusterViSu is
      available under http://cbi-dev.igbmc.fr/cbi/voronoi3D. Supplementary information:
      Supplementary figures are available at Bioinformatics online.

PMID- 29635311
TI  - The Impact of an Electronic Expensive Test Notification.
AB  - Objectives: The impact of clinical decision support tools (CDSTs) that display
      test cost information has been variable. Methods: We retrospectively analyzed the
      3-year impact of a passive CDST that notified providers when the test order cost
      was $1,000 or more. We determined the most common expensive tests ordered, the
      frequency with which providers abandoned the order after notification, and the
      costs saved through this intervention. Results: The average monthly abandonment
      rate was 12.5% (2014), 12.9% (2015), and 14.3% (2016). The cost savings from
      tests not performed for this 3-year period was $696,007. Molecular
      hematopathology assays were the most frequently ordered tests, with variable
      abandonment rates. Conclusions: Although this CDST was passive (ie, could be
      overridden at the point of order entry) and was associated with a relatively low
      abandonment rate, it achieved a considerable cost savings each year since each
      abandoned test saved the institution $1,000 or more.

PMID- 29635312
TI  - Primary Intestinal Epstein-Barr Virus-associated Natural Killer/T-cell
      Lymphoproliferative Disorder: A Disease Mimicking Inflammatory Bowel Disease.
AB  - Background and Aims: Primary intestinal Epstein-Barr virus [EBV]-associated
      natural killer/T-cell lymphoproliferative disorder [PIEBV+ NK/T-LPD] is a rare
      clinical entity, which is difficult to differentiate from inflammatory bowel
      disease [IBD]. We present a series of Chinese patients with PIEBV+ NK/T-LPD to
      increase awareness among clinicians of this condition. Methods: Patients
      diagnosed with PIEBV+ NK/T-LPD at West China hospital between 2014 and 2016 were
      included. Clinical and histopathological characteristics were reviewed, and key
      aspects of differential diagnosis were presented. Results: Twelve patients
      diagnosed with PIEBV+ NK/T-LPD were identified. Initial symptoms included
      intermittent fever [11/12 patients], abdominal pain [9/12], haematochezia [8/12],
      and diarrhoea [3/12]. Main endoscopic findings included multisegmental irregular,
      variable-sized ulcers, isolated giant ulcers, and diffuse inflammation. Colon and
      ileocaecum were mainly affected in 11 patients. The main PIEBV+ NK/T-LPD
      immunophenotypic profile of the infiltrating cells was CD3epsilon-positive NK/T
      cells characterised by positive T-cell intracellular antigen-1 and granzyme B,
      with CD5 deletion. In situ hybridisation was positive for EBV-encoded small RNAs
      1/2 in all patients. Eleven patients were misdiagnosed with ulcerative colitis
      [4/11], Crohn's disease [4/11], or tuberculosis [TB, 3/11], owing to the similar
      endoscopic and histopathological features. The mean number of endoscopic
      procedures performed before reaching the diagnosis of PIEBV+ NK/T-LPD was 3.58;
      in four patients, the diagnosis was confirmed only after surgical resection
      following complications. Conclusions: PIEBV+ NK/T-LPD may be difficult to
      differentiate from IBD or TB owing to overlapping endoscopic and pathological
      findings. Early identification of EBV reactivation in tissue samples is essential
      for the accurate diagnosis.

PMID- 29635314
TI  - Growth characteristics of Chlamydia trachomatis in human intestinal epithelial
      Caco-2 cells.
AB  - Chlamydia trachomatis is an obligate intracellular bacterium causing infections
      of the eyes, urogenital and respiratory tracts. Asymptomatic, repeat and chronic
      infections with C. trachomatis are common in the urogenital tract potentially
      causing severe reproductive pathology. Animal models of infection and
      epidemiological studies suggested the gastrointestinal tract as a reservoir of
      chlamydiae and as a source of repeat urogenital infections. Thus, we investigated
      the growth characteristics of C. trachomatis in human intestinal epithelial Caco
      2 cells and the infection-induced defensin production. Immunofluorescence
      staining and transmission electron microscopy showed the presence of chlamydial
      inclusions in the cells. Chlamydial DNA and viable C. trachomatis were recovered
      from Caco-2 cells in similar quantity compared to that detected in the usual in
      vitro host cell of this bacterium. The kinetics of expression of selected C.
      trachomatis genes in Caco-2 cells indicated prolonged replication with persisting
      high expression level of late genes and of heat shock protein gene groEL.
      Replication of C. trachomatis induced moderate level of beta-defensin-2
      production by Caco-2 cells, which might contribute to avoidance of immune
      recognition in the intestine. According to our results, Caco-2 cells support C.
      trachomatis replication, suggesting that the gastrointestinal tract is a site of
      residence for these bacteria.

PMID- 29635313
TI  - Perspective: Protein Requirements and Optimal Intakes in Aging: Are We Ready to
      Recommend More Than the Recommended Daily Allowance?
AB  - The Dietary Reference Intakes set the protein RDA for persons >19 y of age at 0.8
      g protein ? kg body weight-1 ? d-1. A growing body of evidence suggests, however,
      that the protein RDA may be inadequate for older individuals. The evidence for
      recommending a protein intake greater than the RDA comes from a variety of
      metabolic approaches. Methodologies centered on skeletal muscle are of paramount
      importance given the age-related decline in skeletal muscle mass and function
      (sarcopenia) and the degree to which dietary protein could mitigate these
      declines. In addition to evidence from short-term experimental trials,
      observational data show that higher protein intakes are associated with greater
      muscle mass and, more importantly, better muscle function with aging. We are in
      dire need of more evidence from longer-term intervention trials showing the
      efficacy of protein intakes that are higher than the RDA in older persons to
      support skeletal muscle health. We propose that it should be recommended that
      older individuals consume >=1.2 g protein . kg-1 . d-1 and that there should be
      an emphasis on the intake of the amino acid leucine, which plays a central role
      in stimulating skeletal muscle anabolism. Critically, the often-cited potential
      negative effects of consuming higher protein intakes on renal and bone health are
      without a scientific foundation in humans.

PMID- 29635315
TI  - Elimination of primordial germ cells in sturgeon embryos by ultraviolet
      irradiation.
AB  - A technique for rescuing and propagating endangered species involves implanting
      germ line stem cells into surrogates of a host species whose primordial germ
      cells (PGCs) have been destroyed. We induced sterilization in sterlet (Acipenser
      ruthenus) embryos by means of ultraviolet (UV) irradiation at the vegetal pole,
      the source of early-stage PGCs of sturgeon eggs. The optimal cell stage and
      length of UV irradiation for the effective repression of the developing PGCs were
      determined by exposing embryos at the one- to four-cell stage to different doses
      of irradiation at a wavelength of 254 nm (the optimal absorbance spectrum for
      germplasm destruction). The vegetal pole region of the embryos was labeled
      immediately upon irradiation with GFP bucky ball mRNA to monitor the amount of
      germ plasm and FITC-dextran (M.W. 500,000) to obtain the number of PGCs in the
      embryos. The size of the germ plasm and number of surrounding mitochondria in the
      irradiated embryos and controls were observed using transmission electron
      microscopy, which revealed a drastic reduction in both on the surface of the
      vegetal pole in the treated embryos. Furthermore, the reduction in the number of
      PGCs was proportional to the dose of UV irradiation. Under the conditions tested,
      optimum irradiation for PGCs removal was seen at 360 mJ/cm2 at the one-cell
      stage. Although some PGCs were observed after the UV irradiation, they
      significantly reduced in number as the embryos grew. We conclude that UV
      irradiation is a useful and efficient technique to induce sterility in surrogate
      sturgeons.

PMID- 29635316
TI  - Induction chemotherapy in locally advanced squamous cell carcinoma of the head
      and neck: role, controversy, and future directions.
AB  - Background: The value of induction chemotherapy (ICT) remains under investigation
      despite decades of research. New advancements in the field, specifically
      regarding the induction regimen of choice, have reignited interest in this
      approach for patients with locally advanced squamous cell carcinoma of the head
      and neck (LA SCCHN). Sufficient evidence has accumulated regarding the benefits
      and superiority of TPF (docetaxel, cisplatin, and fluorouracil) over the
      chemotherapy doublet cisplatin and fluorouracil. We therefore sought to collate
      and interpret the available data and further discuss the considerations for
      delivering ICT safely and optimally selecting suitable post-ICT regimens. Design:
      We nonsystematically reviewed published phase III clinical trials on TPF ICT in a
      variety of LA SCCHN patient populations conducted between 1990 and 2017. Results:
      TPF may confer survival and organ preservation benefits in a subgroup of patients
      with functionally inoperable or poor-prognosis LA SCCHN. Additionally, patients
      with operable disease or good prognosis (who are not candidates for organ
      preservation) may benefit from TPF induction in terms of reducing local and
      distant failure rates and facilitating treatment deintensification in selected
      populations. The safe administration of TPF requires treatment by a
      multidisciplinary team at an experienced institution. The management of adverse
      events associated with TPF and post-ICT radiotherapy-based treatment is crucial.
      Finally, post-ICT chemotherapy alternatives to cisplatin concurrent with
      radiotherapy (i.e. cetuximab or carboplatin plus radiotherapy) appear promising
      and must be investigated further. Conclusions: TPF is an evidence-based ICT
      regimen of choice in LA SCCHN and confers benefits in suitable patients when it
      is administered safely by an experienced multidisciplinary team and paired with
      the optimal post-ICT regimen, for which, however, no consensus currently exists.

PMID- 29635317
TI  - The latent geometry of the human protein interaction network.
AB  - Motivation: A series of recently introduced algorithms and models advocates for
      the existence of a hyperbolic geometry underlying the network representation of
      complex systems. Since the human protein interaction network (hPIN) has a complex
      architecture, we hypothesized that uncovering its latent geometry could ease
      challenging problems in systems biology, translating them into measuring
      distances between proteins. Results: We embedded the hPIN to hyperbolic space and
      found that the inferred coordinates of nodes capture biologically relevant
      features, like protein age, function and cellular localization. This means that
      the representation of the hPIN in the two-dimensional hyperbolic plane offers a
      novel and informative way to visualize proteins and their interactions. We then
      used these coordinates to compute hyperbolic distances between proteins, which
      served as likelihood scores for the prediction of plausible protein interactions.
      Finally, we observed that proteins can efficiently communicate with each other
      via a greedy routing process, guided by the latent geometry of the hPIN. We show
      that these efficient communication channels can be used to determine the core
      members of signal transduction pathways and to study how system perturbations
      impact their efficiency. Availability and implementation: An R implementation of
      our network embedder is available at https://github.com/galanisl/NetHypGeom.
      Also, a web tool for the geometric analysis of the hPIN accompanies this text at
      http://cbdm-01.zdv.uni-mainz.de/~galanisl/gapi. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 29635318
TI  - The Voice of the Consumer: A Survey of Veterans and Other Users of Assistive
      Technology.
AB  - Introduction: A total of 3.6 million Americans and over 250,000 veterans use
      wheelchairs. The need for advancements in mobility-assistive technologies is
      continually growing due to advances in medicine and rehabilitation that preserve
      and prolong the lives of people with disabilities, increases in the senior
      population, and increases in the number of veterans and civilians involved in
      conflict situations. The purpose of this study is to survey a large sample of
      veterans and other consumers with disabilities who use mobility-assistive
      technologies to identify priorities for future research and development.
      Materials and Methods: This survey asked participants to provide opinions on the
      importance of developing various mobility-assistive technologies and to rank the
      importance of certain technologies. Participants were also asked to provide open
      ended comments and suggestions. Results: A total of 1,022 individuals, including
      500 veterans, from 49 states within the USA and Puerto Rico completed the survey.
      The average age of respondents was 54.3 yr, and they represented both new and
      experienced users of mobility-assistive technologies. The largest diagnostic
      group was spinal cord injury (SCI) (N = 491, 48.0%). Several themes on critical
      areas of research emerged from the open-ended questions, which generated a total
      of 1,199 comments. Conclusion: This survey revealed several themes for future
      research and development. Advanced wheelchair design, smart device applications,
      human-machine interfaces, and assistive robotics and intelligent systems emerged
      as priorities. Survey results also demonstrated the importance for researchers to
      understand the effects of policy and cost on translational research and to be
      involved in educating both consumers and providers.

PMID- 29635320
TI  - Simultaneous HPLC Determination of Cisatracurium and Propofol in Human Plasma via
      Fluorometric Detection.
AB  - The proposed method describes a high performance liquid chromatographic method
      with fluoremetric detection for the determination of cisatracurium (CIS) and
      propofol (PRP) simultaneously, which are co-administered as a pre-operative
      injection mixture. The separation of the two drugs was achieved using monolithic
      column (100 mm and 4.6 mm internal diameter) and mixture of methanol and 0.1 M
      phosphate buffer in the ratio of 80:20 (v/v) at pH 4.5 as a mobile phase. The
      fluorescence detection was carried out at 230/324 nm. The procedure showed good
      linearity through the concentration ranges of 0.01-1.00 MUg/mL and 0.1-3.0 MUg/mL
      with limits of detection of 0.002, 0.030 MUg/mL and limits of quantification of
      0.006, 0.100 MUg/mL for CIS and PRP, respectively. Simultaneous determination of
      CIS and PRP in spiked human plasma samples was additionally executed and the
      results were satisfactory precise and accurate.

PMID- 29635319
TI  - Cortico-Amygdala-Striatal Activation by Modafinil/Flecainide Combination.
AB  - Background: Modafinil, a nonamphetaminic wake-promoting compound, is prescribed
      as first line therapy in narcolepsy, an invalidating disorder characterized by
      excessive daytime sleepiness and cataplexy. Although its mode of action remains
      incompletely known, recent studies indicated that modafinil modulates astroglial
      connexin-based gap junctional communication as administration of a low dose of
      flecainide, an astroglial connexin inhibitor, enhanced the wake-promoting and
      procognitive activity of modafinil in rodents and healthy volunteers. The aim of
      this study is to investigate changes in glucose cerebral metabolism in rodents,
      induced by the combination of modafinil+flecainide low dose (called THN102).
      Methods: The impact of THN102 on brain glucose metabolism was noninvasively
      investigated using 18F-2-fluoro-2-deoxy-D-glucose Positron Emission Tomography
      imaging in Sprague-Dawley male rats. Animals were injected with vehicle,
      flecainide, modafinil, or THN102 and further injected with 18F-2-fluoro-2-deoxy-D
      glucose followed by 60-minute Positron Emission Tomography acquisition. 18F-2
      fluoro-2-deoxy-D-glucose Positron Emission Tomography images were coregistered to
      a rat brain template and normalized from the total brain Positron Emission
      Tomography signal. Voxel-to-voxel analysis was performed using SPM8 software.
      Comparison of brain glucose metabolism between groups was then performed.
      Results: THN102 significantly increased regional brain glucose metabolism as it
      resulted in large clusters of 18F-2-fluoro-2-deoxy-D-glucose uptake localized in
      the cortex, striatum, and amygdala compared with control or drugs administered
      alone. These regions, highly involved in the regulation of sleep-wake cycle,
      emotions, and cognitive functions were hence quantitatively modulated by THN102.
      Conclusion: Data presented here provide the first evidence of a regional brain
      activation induced by THN102, currently being tested in a phase II clinical trial
      in narcoleptic patients.

PMID- 29635322
TI  - Atrial approaches to the mitral valve: is there a difference in postoperative
      rhythm disturbance and permanent pacemaker implantation?
AB  - A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed was whether there was a difference in
      postoperative outcomes [namely permanent pacemaker (PPM) insertion, rhythm
      disturbance, reoperation for bleeding, hospital stay and in-hospital mortality]
      between trans-septal or superior (extended) trans-septal (STS) approaches in
      comparison with the conventional left atriotomy (LA) used in mitral valve
      surgery. Using the reported search strategy, 353 papers were found of which 11
      represented the best evidence to answer the clinical question. The authors,
      journal, year and country of publication, patient group studied, study type,
      relevant outcomes and results of these papers are tabulated. Two papers compared
      all 3 atrial incisions with neither showing a difference in PPM implantation
      rate, whereas 2 papers compared just the trans-septal with the LA approach, again
      both finding no significant difference in PPM implantation. Seven studies
      compared the STS approach with the LA approach with regard to PPM implantation; 1
      study showed that the STS approach was an independent risk factor for PPM
      implantation, PPM insertion was not necessary in 2 studies and there was no
      difference in PPM insertion in 4 studies. Postoperative junctional rhythm was
      studied in 5 papers that compared the STS approach with the LA approach;
      junctional rhythm was more prevalent in the STS approach in 2 studies, albeit
      transient, whereas 3 papers did not show a significant difference. Mortality,
      hospital stay and re-exploration for bleeding did not differ among the 3 groups.

PMID- 29635321
TI  - Inhibition of transient receptor potential melastatin 8 alleviates airway
      inflammation and remodeling in a murine model of asthma with cold air stimulus.
AB  - Cold air stimulus is an important environmental factor that exacerbates asthma.
      At the molecular level, the transient receptor potential melastatin 8 (TRPM8)
      plays a crucial part in cold detection. The roles of TRPM8 in airway inflammation
      and remodeling in a murine model of asthma with cold stimulus and the related
      molecular mechanism are largely unknown. In this study, C57BL/6 mice were
      randomly divided into four groups: phosphate-buffered saline control group
      (control), ovalbumin (OVA)-induced asthma group (OVA), OVA with cold air stimulus
      group (OVA+cold), and OVA+cold+shTRPM8 (TRPM8 short hairpin RNA) group. We showed
      that cold air stimulus-induced TRPM8 upregulation in the OVA+cold group.
      Moreover, TRPM8 knockdown significantly attenuated cold-induced inflammation and
      infiltration, decreased levels of immunoglobulin E, restored the Th1/Th2 balance,
      and reduced inflammatory cell accumulation and airway remodeling. Furthermore, we
      demonstrated that TRPM8 knockdown dramatically inhibited mitogen-activated
      protein kinase and nuclear factor-kappaB pathways. Collectively, these results
      revealed that cold air stimulus induced an airway inflammatory response and
      remodeling by increasing TRPM8 expression and that downregulation of TRPM8
      alleviated these responses.

PMID- 29635323
TI  - Myocardial fibrosis as an early feature in phospholamban p.Arg14del mutation
      carriers: phenotypic insights from cardiovascular magnetic resonance imaging.
AB  - Aims: The p.Arg14del founder mutation in the gene encoding phospholamban (PLN) is
      associated with an increased risk of malignant ventricular arrhythmia (VA) and
      heart failure. It has been shown to lead to calcium overload, cardiomyocyte
      damage, and eventually to myocardial fibrosis. This study sought to investigate
      ventricular function, the extent and localization of myocardial fibrosis and the
      associations with ECG features and VA in PLN p.Arg14del mutation carriers.
      Methods and results: Cardiovascular magnetic resonance (CMR) data of 150 mutation
      carriers were analysed retrospectively. Left ventricular (LV) and right
      ventricular (RV) volumes, mass, and ejection fraction were measured. The extent
      of late gadolinium enhancement (LGE) was expressed as a percentage of myocardial
      mass. All standard ECG parameters were measured. Occurrence of VA was analysed on
      ambulatory 24-h and/or exercise electrocardiography, if available. Mean age was
      40 +/- 15 years, 42% males, and 7% were index patients while 93% were pre
      symptomatic carriers identified after family cascade screening. Mean LV ejection
      fraction (LVEF) and RV ejection fraction were 58 +/- 9% and 55 +/- 9%,
      respectively. LV-LGE was present in 91% of mutation carriers with reduced LVEF
      (<45%) and in 30% of carriers with preserved LVEF. In carriers with positive LV
      LGE, its median extent was 5.9% (interquartile range 3.2-12.7). LGE was mainly
      observed in the inferolateral wall. Carriers with inverted T-waves in the lateral
      ECG leads more often had LV-LGE (P < 0.01) than carriers without. Finally, the
      presence of LV-LGE, but not attenuated R-waves and inverted lateral T-waves, was
      independently associated with VA. Conclusion: LV myocardial fibrosis is present
      in many PLN p.Arg14del mutation carriers, and who still have a preserved LVEF. It
      is seen predominantly in the LV inferolateral wall and corresponds with
      electrocardiographic repolarization abnormalities. Although preliminary,
      myocardial fibrosis was found to be independently associated with VA. Our
      findings support the use of CMR with LGE early in the diagnostic work-up.

PMID- 29635324
TI  - Biceps Tendon Sheath Injection: An Anatomical Conundrum.
AB  - Objective: Long head biceps tendon peritendinous or sheath injections are
      routinely administered at or immediately distally to the bicipital groove. The
      main indication for injection remains the clinical diagnosis or treatment of
      biceps tendinopathy, although true inflammation of the tendon within the
      bicipital groove is rare. Because the tendon sheath is merely an extension of the
      joint cavity, it is plausible to assume that an injection into the sheath would
      result in intraarticular spread. Surprisingly, such an anatomical tenet has a
      vague confirmation in the published clinical literature. This experiment was
      undertaken to investigate patterns of injectate spread when peri-tendon injection
      at the bicipital groove is performed. Design: An experimental cadaveric study.
      Setting: An institutional clinical anatomy laboratory. Methods: Twelve ultrasound
      guided methylene blue injections of the bicep tendon sheath were performed on
      cadaver specimens. Dissections and gross examination of staining of the internal
      joint surfaces were performed. Visual confirmation of the intra- and/or extra
      articular spread of the injectate was performed. Results: In 11 specimens,
      injected contrast was found spreading onto the entire internal joint surface,
      including glenoid cartilage. One extraarticular injection was attributable to a
      technical issue. Conclusions: The experiment confirmed continuity of the joint
      capsule and the biceps tendon sheath. These results suggest a low diagnostic
      utility of peritendinous injections at the level of the bicep groove. Such
      injections would likely result in intraarticular deposit of the injectate.
      Nonetheless, this approach may be utilized as an alternative simplified access to
      the glenohumeral joint.

PMID- 29635325
TI  - The effect of cellobiose on the health status of growing rabbits depends on the
      dietary level of soluble fiber.
AB  - The aim of this study was to examine whether the combination of dietary soluble
      fiber and cellobiose exerts a synergistic effect on growth performance, health
      status, fermentation traits, and immune response in rabbits. Six treatments in a
      3 * 2 factorial arrangement were used: 3 cellobiose concentrations in drinking
      water (0.0, 7.5, and 15.0 g/L) * 2 dietary levels of soluble fiber (84.0 and 130
      g/kg DM, for the low soluble fiber [LSF] and high soluble fiber [HSF] diets,
      respectively). A total of 318 young rabbits (53/treatment) were weaned at 34 d of
      age and had ad libitum access to feed and water. At 46 d of age, 9
      rabbits/treatment were slaughtered and ileal and cecal digesta were collected to
      analyze VFA profile and the immune response in the cecal appendix mucosa. At 48 d
      of age, the cellobiose supplementation was withdrawn and the experimental diets
      were replaced by a standard commercial diet until 61 d of age. From 34 to 48 d of
      age, there was a linear increase of mortality with the level of cellobiose in the
      HSF group (0% vs. 17.1%; P = 0.017). In contrast, a quadratic effect of
      cellobiose level on mortality was observed in the LSF group, the rabbits offered
      7.5-cellobiose showing the lowest mortality (5.7% vs. 21.4%; P = 0.030).
      Cellobiose level had a quadratic effect on ADFI, ADG, and G:F in this period (P
      <= 0.047), with the 7.5-cellobiose groups having the best growth performance. In
      contrast, only minor changes on these traits were observed from 48 d of age
      onwards. Cellobiose level influenced quadratically the ileal VFA concentrations
      (P = 0.014), showing the maximal value in the 7.5-cellobiose groups. In rabbits
      fed 7.5-cellobiose-LSF, a change of acetate to propionate, butyrate, and valerate
      was observed in the ileum. Increasing cellobiose levels reduced linearly cecal
      VFA concentrations in HSF fed rabbits, but no effect was detected in LSF groups
      (P = 0.046). The level of soluble fiber increased VFA concentrations in both the
      ileum (by 22%; P < 0.001), and the cecum (by 11%; P = 0.005). The relative gene
      expression of IL-6, IL-10, TNF-alpha, iNOS, MUC-1, and toll-like receptors (TLR-2
      and TLR-4) in the cecal appendix increased linear and quadratically with
      increasing levels of cellobiose (P <= 0.063). In conclusion, in rabbits fed LSF
      diets, a dose of 7.5 g cellobiose/L drinking water would be recommended, whereas
      these levels of cellobiose supplementation should be avoided in rabbits fed HSF
      diets.

PMID- 29635326
TI  - Landscape Effects on Reproduction of Euschistus servus (Hemiptera: Pentatomidae),
      a Mobile, Polyphagous, Multivoltine Arthropod Herbivore.
AB  - Landscape factors can significantly influence arthropod populations. The
      economically important brown stink bug, Euschistus servus (Say) (Hemiptera:
      Pentatomidae), is a native mobile, polyphagous and multivoltine pest of many
      crops in southeastern United States and understanding the relative influence of
      local and landscape factors on their reproduction may facilitate population
      management. Finite rate of population increase (lambda) was estimated in four
      major crop hosts-maize, peanut, cotton, and soybean-over 3 yr in 16 landscapes of
      southern Georgia. A geographic information system (GIS) was used to characterize
      the surrounding landscape structure. LASSO regression was used to identify the
      subset of local and landscape characteristics and predator densities that account
      for variation in lambda. The percentage area of maize, peanut and woodland and
      pasture in the landscape and the connectivity of cropland had no influence on E.
      servus lambda. The best model for explaining variation in lambda included only
      four predictor variables: whether or not the sampled field was a soybean field,
      mean natural enemy density in the field, percentage area of cotton in the
      landscape and the percentage area of soybean in the landscape. Soybean was the
      single most important variable for determining E. servus lambda, with much
      greater reproduction in soybean fields than in other crop species. Penalized
      regression and post-selection inference provide conservative estimates of the
      landscape-scale determinants of E. servus reproduction and indicate that a
      relatively simple set of in-field and landscape variables influences reproduction
      in this species.

PMID- 29635327
TI  - Use of a Lysine-Derived Urethane Surgical Adhesive as an Alternative to
      Progressive Tension Sutures in Abdominoplasty Patients: A Cohort Study.
AB  - Background: Fluid accumulation is a common complication after abdominoplasty
      procedures, and is typically managed by the placement of post-surgical drains.
      Progressive tension sutures (PTS) have been shown to be an effective approach to
      reduce the dead space by point-wise mechanical fixation, allowing for drain-free
      procedures. Lysine-derived urethane surgical adhesive provides an alternative
      approach for mechanical fixation and reduction of dead space, and may reduce
      surgery time compared to PTS. Objectives: This prospective, controlled, single
      center clinical study compared progressive tension suture wound closure technique
      without drains (control) to tissue adhesive wound closure technique without
      drains (test) during abdominoplasty surgery. The objective was to determine if
      lysine-derived urethane surgical adhesive is an effective alternative to PTS for
      drain-free abdominoplasty procedures. Methods: Patients undergoing abdominoplasty
      who met the established inclusion/exclusion criteria were consented and enrolled
      in the study. Ten PTS (control) cases were performed, followed immediately by 10
      tissue adhesive (test) cases. Results: Surgeries were completed over an 8-month
      period. No statistical differences were identified between the two groups with
      regard to age, BMI, dissection surface area or flap weight. No clinical seroma
      formation was observed in either group. In the control (PTS) group, two patients
      developed small areas of dermal closure suture abscess requiring removal of
      suture material. One control patient developed drainage and fat necrosis thought
      to be related to PTS above the incision and later required a scar revision. One
      tissue adhesive patient developed hypertrophic scars of both her breast reduction
      and abdominoplasty scars requiring additional treatment. Conclusions: Lysine
      derived urethane surgical adhesive was applied in less time than PTS, even after
      accounting for holding pressure for 5 minutes. The tissue adhesive provided four
      times the number of attachment points compared to PTS, although the significance
      of this is not clear. Based on these results, the use of lysine-derived urethane
      surgical adhesive was found to be a safe and effective alternative to PTS to
      reduce seroma formation in drain-free abdominoplasty procedures. Level of
      Evidence 2: 

PMID- 29635328
TI  - Genetic Diversity on the Sex Chromosomes.
AB  - Levels and patterns of genetic diversity can provide insights into a population's
      history. In species with sex chromosomes, differences between genomic regions
      with unique inheritance patterns can be used to distinguish between different
      sets of possible demographic and selective events. This review introduces the
      differences in population history for sex chromosomes and autosomes, provides the
      expectations for genetic diversity across the genome under different evolutionary
      scenarios, and gives an introductory description for how deviations in these
      expectations are calculated and can be interpreted. Predominantly, diversity on
      the sex chromosomes has been used to explore and address three research areas: 1)
      Mating patterns and sex-biased variance in reproductive success, 2) signatures of
      selection, and 3) evidence for modes of speciation and introgression. After
      introducing the theory, this review catalogs recent studies of genetic diversity
      on the sex chromosomes across species within the major research areas that sex
      chromosomes are typically applied to, arguing that there are broad similarities
      not only between male-heterogametic (XX/XY) and female-heterogametic (ZZ/ZW) sex
      determination systems but also any mating system with reduced recombination in a
      sex-determining region. Further, general patterns of reduced diversity in
      nonrecombining regions are shared across plants and animals. There are unique
      patterns across populations with vastly different patterns of mating and
      speciation, but these do not tend to cluster by taxa or sex determination system.

PMID- 29635329
TI  - Large Diversity of Nonstandard Genes and Dynamic Evolution of Chloroplast Genomes
      in Siphonous Green Algae (Bryopsidales, Chlorophyta).
AB  - Chloroplast genomes have undergone tremendous alterations through the
      evolutionary history of the green algae (Chloroplastida). This study focuses on
      the evolution of chloroplast genomes in the siphonous green algae (order
      Bryopsidales). We present five new chloroplast genomes, which along with existing
      sequences, yield a data set representing all but one families of the order. Using
      comparative phylogenetic methods, we investigated the evolutionary dynamics of
      genomic features in the order. Our results show extensive variation in
      chloroplast genome architecture and intron content. Variation in genome size is
      accounted for by the amount of intergenic space and freestanding open reading
      frames that do not show significant homology to standard plastid genes. We show
      the diversity of these nonstandard genes based on their conserved protein
      domains, which are often associated with mobile functions (reverse
      transcriptase/intron maturase, integrases, phage- or plasmid-DNA primases,
      transposases, integrases, ligases). Investigation of the introns showed
      proliferation of group II introns in the early evolution of the order and their
      subsequent loss in the core Halimedineae, possibly through RT-mediated intron
      loss.

PMID- 29635330
TI  - Live growth performance, carcass grading characteristics, and harvest yields of
      beef steers supplemented zilpaterol hydrochloride and offered ad libitum or
      maintenance energy intake.
AB  - A trial was conducted to examine live growth efficiency, harvest yields, and
      carcass grading performance of steers fed at maintenance (M) or at ad libitum (A)
      level of intake during zilpaterol hydrochloride (Z) supplementation. Single
      sired, beef steers (n = 56; start of trial BW 590 +/- 36 kg) blocked (n = 2) by
      weight and terminal implant were sorted into pairs (n = 14 per block) by weight.
      Pairs of steers were initially assigned to 0, 28, or 56 d of feeding. Within 28
      or 56 d, pairs were assigned to M or A intake. Steers within a pair assigned to
      56 d of feeding were randomly assigned to either 20 d of Z supplementation (90
      mg/d per steer) with a 4 d withdrawal period prior to slaughter or to no ZH
      supplementation (C). Steers were housed and fed in individual pens. Weights of
      all non-carcass and carcass components were recorded at slaughter; carcasses were
      graded 24-h postmortem. Data were analyzed via a mixed model; the fixed effect
      was treatment combination with random effects of block and pair. Live growth data
      used harvest day as the repeated measure and animal as the subject. Single df
      contrasts were constructed for day 0 vs. day 28, day 0 vs. day 56, day 28 vs. day
      56, M vs. A, and C vs. Z. Treatment impacted (P <= 0.05) live ADG; contrasts
      indicated A (1.33) was greater than M (0.14 kg), and Z (1.12) was greater than C
      (0.82 kg). Similarly, carcass ADG differences (P < 0.01) indicated A (1.04) was
      greater than M (0.36 kg), and Z (1.35) was greater than C (0.71 kg). Intake level
      altered BW and empty body weight (EBW); M cattle had reduced BW and EBW (P <
      0.01, 585 and 540 kg) than A cattle (647 and 597 kg). Cattle fed at M had less
      carcass and internal cavity mass (P < 0.01, 359 and 79.4 kg) than A cattle (394
      and 93.5 kg). Liver mass was reduced by M feeding (P < 0.01; M-5.03, A-6.69 kg)
      and Z treatment (P < 0.01; Z-5.64, C-6.06 kg). Moreover, mass of total splanchnic
      tissue was less (P < 0.01) for M cattle than A cattle (59.8 vs. 72.5 kg). Dressed
      carcass yield was greater (P < 0.01) for Z than C cattle (63.5 vs. 61.6%). Cattle
      fed at M had less 12th rib s.c. fat, lower numerical U.S. yield grades (P < 0.01;
      M-1.71 cm and 3.3, A-2.46 cm and 4.3) and lower numerical Canadian yield grades
      (P < 0.01; 51.9 vs. 53.9% for M and A, respectively) than A cattle. Results
      indicate that energy intake level and Z supplementation influence live and
      carcass growth, carcass transfer, kill yields, and carcass characteristics across
      time.

PMID- 29635331
TI  - Response to K. Hemminki et al.

PMID- 29635332
TI  - Contribution of Smoking to Tuberculosis Incidence and Mortality in High
      Tuberculosis-Burden Countries.
AB  - Globally, 10 million incident cases of tuberculosis (TB) are reported annually,
      and 95% of TB cases and 80% of tobacco users reside in low- and middle-income
      countries. Smoking approximately doubles the risk of TB disease and TB mortality.
      We estimated the proportion of annual incident TB cases and TB mortality
      attributable to tobacco smoking in 32 high-TB-burden countries. We obtained
      country-specific estimates of TB incidence, TB mortality, and smoking prevalence
      from the World Health Organization Global TB Report (2017), tobacco surveillance
      reports (2015), and the Tobacco Atlas. Risk ratios for the effect of smoking on
      TB incidence and TB mortality were obtained from published meta-analyses. An
      estimated 17.6% (95% confidence interval (CI): 8.4, 21.4) of TB cases and 15.2%
      (95% CI: 1.8, 31.9) of TB mortality were attributable to smoking. Among high-TB
      burden countries, Russia had the highest proportion of smoking-attributable TB
      disease (31.6%, 95% CI: 15.9, 37.6) and deaths (28.1%, 95% CI: 3.8, 51.4). Men
      had a greater proportion of TB cases attributable to smoking (30.3%, 95% CI:
      14.7, 36.6) than did women (4.3, 95% CI: 1.7, 5.7). Our findings highlight the
      need for tobacco control in high-TB-burden countries to combat TB incidence and
      TB mortality.

PMID- 29635334
TI  - Clinical Significance of Human Herpesvirus 6 Positivity on the FilmArray
      Meningitis/Encephalitis Panel.
AB  - A review of 15 patients who tested positive for human herpesvirus 6 (HHV-6) on
      the FilmArray Meningitis/Encephalitis panel revealed that the majority were
      unlikely to have HHV-6 encephalitis. Criteria to assist interpretation of HHV-6
      positive results are presented.

PMID- 29635333
TI  - Genes from the TAS1R and TAS2R Families of Taste Receptors: Looking for
      Signatures of Their Adaptive Role in Human Evolution.
AB  - Taste perception is crucial in monitoring food intake and, hence, is thought to
      play a significant role in human evolution. To gain insights into possible
      adaptive signatures in genes encoding bitter, sweet, and umami taste receptors,
      we surveyed the available sequence variation data from the 1000 Genomes Project
      Phase 3 for TAS1R (TAS1R1-3) and TAS2R (TAS2R16 and TAS2R38) families. Our study
      demonstrated that genes from these two families have experienced contrasting
      evolutionary histories: While TAS1R1 and TAS1R3 showed worldwide evidence of
      positive selection, probably correlated with improved umami and sweet perception,
      the patterns of variation displayed by TAS2R16 and TAS2R38 were more consistent
      with scenarios of balancing selection that possibly conferred a heterozygous
      advantage associated with better capacity to perceive a wide range of bitter
      compounds. In TAS2R16, such adaptive events appear to have occurred restrictively
      in mainland Africa, whereas the strongest evidence in TAS2R38 was detected in
      Europe. Despite plausible associations between taste perception and the TAS1R and
      TAS2R selective signatures, we cannot discount other biological mechanisms as
      driving the evolutionary trajectories of those TAS1R and TAS2R members,
      especially given recent findings of taste receptors behaving as the products of
      pleiotropic genes involved in many functions outside the gustatory system.

PMID- 29635335
TI  - Risk profile, quality of life and care of patients with moderate and advanced CKD
      : The French CKD-REIN Cohort Study.
AB  - Background: The French Chronic Kidney Disease-Renal Epidemiology and Information
      Network (CKD-REIN) cohort study was designed to investigate the determinants of
      prognosis and care of patients referred to nephrologists with moderate and
      advanced chronic kidney disease (CKD). We examined their baseline risk profile
      and experience. Methods: We collected bioclinical and patient-reported
      information from 3033 outpatients with CKD and estimated glomerular filtration
      rates (eGFRs) of 15-60 mL/min/1.73 m2 treated at 40 nationally representative
      public and private facilities. Results: The patients' median age was 69 (60-76)
      years, 65% were men, their mean eGFR was 33 mL/min/1.73 m2, 43% had diabetes, 24%
      had a history of acute kidney injury (AKI) and 57% had uncontrolled blood
      pressure (BP; >140/90 mmHg). Men had worse risk profiles than women and were more
      likely to be past or current smokers (73% versus 34%) and have cardiovascular
      disease (59% versus 42%), albuminuria >30 mg/mmol (or proteinuria > 50) (40%
      versus 30%) (all P < 0.001) and a higher median risk of end-stage renal disease
      within 5 years, predicted by the kidney failure risk equation {12% [interquartile
      range (IQR) 3-37%] versus 9% [3-31%], P = 0.008}. During the previous year, 60%
      of patients reported one-to-two nephrologist visits and four or more general
      practitioner visits; only 25% saw a dietician and 75% were prescribed five or
      more medications daily. Physical and mental quality of life (QoL) were poor, with
      scores <50/100. Conclusions: The CKD-REIN study highlights high-risk profiles of
      cohort members and identifies several priorities, including improving BP control
      and dietary counselling and increasing doctors' awareness of AKI, polypharmacy
      and QoL. Trial registration: ClinicalTrials.gov identifier: NCT03381950.

PMID- 29635336
TI  - A systematic approach to develop a core set of parameters for boards of directors
      to govern quality of care in the ICU.
AB  - Objective: Hospital boards are legally responsible for the quality of care
      delivered by healthcare professionals in their hospitals, but experience
      difficulties in overseeing quality and safety risks. This study aimed to select a
      core set of parameters for boards to govern quality of care in the intensive care
      unit (ICU). Design: Two-round Delphi study. Setting: Two university hospitals in
      the Netherlands. Participants: An expert panel of 12 former ICU patients or their
      family members, 12 ICU nurses, 12 ICU physicians and 12 members of boards of
      directors and quality managers. Main outcome measures: Participants indicated the
      relevance of existing parameters for assessing the quality of ICU care for
      governance purposes (round 1) and selected 10 quality parameters that together
      provide boards of directors with a good representation of quality of care in
      their ICU (round 2). Results: We identified 122 quality parameters related to
      care in the ICU, which we limited to a short list to present to participants in
      round 1. The response rate was 94% in round 1 and 85% in round 2. The final set
      consisted of the 10 most frequently selected quality parameters per hospital.
      Five parameters were included in both sets; all related to patient safety and
      continuous quality improvement. Conclusions: Parameters in the core set were
      mostly qualitative and generic, rather than quantitative and ICU-specific in
      nature. To engage in a true dialog about quality of care, boards are more
      interested in the story behind the numbers than in just the numbers themselves.

PMID- 29635337
TI  - RE: Familial Cancer Clustering of Urothelial Cancer: A Population-Based Case
      Control Study.

PMID- 29635338
TI  - Increased cardiac fatty acid oxidation in a mouse model with decreased malonyl
      CoA sensitivity of CPT1B.
AB  - Aims: Mitochondrial fatty acid oxidation (FAO) is an important energy provider
      for cardiac work and changes in cardiac substrate preference are associated with
      different heart diseases. Carnitine palmitoyltransferase 1B (CPT1B) is thought to
      perform the rate limiting enzyme step in FAO and is inhibited by malonyl-CoA. The
      role of CPT1B in cardiac metabolism has been addressed by inhibiting or
      decreasing CPT1B protein or after modulation of tissue malonyl-CoA metabolism. We
      assessed the role of CPT1B malonyl-CoA sensitivity in cardiac metabolism. Methods
      and results: We generated and characterized a knock in mouse model expressing the
      CPT1BE3A mutant enzyme, which has reduced sensitivity to malonyl-CoA. In isolated
      perfused hearts, FAO was 1.9-fold higher in Cpt1bE3A/E3A hearts compared with
      Cpt1bWT/WT hearts. Metabolomic, proteomic and transcriptomic analysis showed
      increased levels of malonylcarnitine, decreased concentration of CPT1B protein
      and a small but coordinated downregulation of the mRNA expression of genes
      involved in FAO in Cpt1bE3A/E3A hearts, all of which aim to limit FAO. In vivo
      assessment of cardiac function revealed only minor changes, cardiac hypertrophy
      was absent and histological analysis did not reveal fibrosis. Conclusions:
      Malonyl-CoA-dependent inhibition of CPT1B plays a crucial role in regulating FAO
      rate in the heart. Chronic elevation of FAO has a relatively subtle impact on
      cardiac function at least under baseline conditions.

PMID- 29635339
TI  - Screening oligonucleotide sequences for silver staining and d-galactose visual
      detection using RCA silver staining in a tube.
AB  - Oligonucleotides were screened for strongly silver-stained repetitive sequences.
      An 'AG'-clustered purine sequence showed strong staining, and the staining
      density can be compromised by disrupting the continuity of the 'AG'-clustered
      sequence. The staining-favored sequence was then employed in rolling circle
      amplification (RCA) for its product detection. A tube-staining method was
      developed for convenient and visual RCA assay. Moreover, by introducing GalR into
      RCA, d-galactose was detected by RCA tube-staining with naked eyes without any
      equipment. About 10 mM d-galactose can be easily identified, and the detection of
      d-galactose was specific in comparison with that of several other
      monosaccharides.

PMID- 29635341
TI  - Motivation for Writing.

PMID- 29635340
TI  - Structurally Related Kappa Opioid Receptor Agonists with Substantial Differential
      Signaling Bias: Neuroendocrine and Behavioral Effects in C57BL6 Mice.
AB  - Background: The kappa opioid receptor system has been revealed as a potential
      pharmacotherapeutic target for the treatment of addictions to substances of
      abuse. Kappa opioid receptor agonists have been shown to block the rewarding and
      dopamine-releasing effects of psychostimulants. Recent investigations have
      profiled the in vivo effects of compounds biased towards G-protein-mediated
      signaling, with less potent arrestin-mediated signaling. The compounds studied
      here derive from a series of trialkylamines: N-substituted-N- phenylethyl-N-3
      hydroxyphenylethyl-amine, with N-substituents including n-butyl (BPHA),
      methylcyclobutyl (MCBPHA), and methylcyclopentyl (MCPPHA). Methods: BPHA, MCBPHA,
      and MCPPHA were characterized in vitro in a kappa opioid receptor-expressing cell
      line in binding assays and functional assays. We also tested the compounds in
      C57BL6 mice, assaying incoordination with rotarod, as well as circulating levels
      of the neuroendocrine kappa opioid receptor biomarker, prolactin. Results: BPHA,
      MCBPHA, and MCPPHA showed full kappa opioid receptor agonism for G-protein
      coupling compared with the reference compound U69,593. BPHA showed no measurable
      beta-arrestin-2 recruitment, indicating that it is extremely G-protein biased.
      MCBPHA and MCPPHA, however, showed submaximal efficacy for recruiting beta
      arrestin-2. Studies in C57BL6 mice reveal that all compounds stimulate release of
      prolactin, consistent with dependence on G-protein signaling. MCBPHA and MCPPHA
      result in rotarod incoordination, whereas BPHA does not, consistent with the
      reported requirement of intact kappa opioid receptor/beta-arrestin-2 mediated
      coupling for kappa opioid receptor agonist-induced rotarod incoordination.
      Conclusions: BPHA, MCBPHA, and MCPPHA are thus novel differentially G-protein
      biased kappa opioid receptor agonists. They can be used to investigate how
      signaling pathways mediate kappa opioid receptor effects in vitro and in vivo and
      to explore the effects of candidate kappa opioid receptor-targeted
      pharmacotherapeutics.

PMID- 29635342
TI  - Editorial: Mapping microbiology with scientometrics - help provide a clearer
      vision of microbiology research around the globe.

PMID- 29635343
TI  - Decision-Making in Adolescents with Profound Hearing Loss.
AB  - People with profound hearing loss show differences in language-related cognitive
      functions that may affect decision-making processes, but few studies have
      examined their decision-making behavior. The current study used the Iowa Gambling
      Task and the Game of Dice Task to explore the decision-making characteristics of
      adolescents with profound hearing loss. In the Iowa Gambling Task, deaf
      adolescents were more inclined to choose from the deck of infrequent losses with
      large immediate gains and larger future losses. In the Game of Dice Task, the
      deaf adolescents showed a preference for high-risk choices with high gains and
      high losses. These results suggest that deaf adolescents show a stronger
      preference for choices with immediate high gains and underestimate the potential
      risks, which may be related to differences in executive function or utilization
      of feedback.

PMID- 29635344
TI  - Histone H3 lysine 36 methyltransferase mobilizes NER factors to regulate
      tolerance against alkylation damage in fission yeast.
AB  - The Set2 methyltransferase and its target, histone H3 lysine 36 (H3K36), affect
      chromatin architecture during the transcription and repair of DNA double-stranded
      breaks. Set2 also confers resistance against the alkylating agent, methyl
      methanesulfonate (MMS), through an unknown mechanism. Here, we show that
      Schizosaccharomyces pombe (S. pombe) exhibit MMS hypersensitivity when expressing
      a set2 mutant lacking the catalytic histone methyltransferase domain or a H3K36R
      mutant (reminiscent of a set2-null mutant). Set2 acts synergistically with base
      excision repair factors but epistatically with nucleotide excision repair (NER)
      factors, and determines the timely nuclear accumulation of the NER initiator,
      Rhp23, in response to MMS. Set2 facilitates Rhp23 recruitment to chromatin at the
      brc1 locus, presumably to repair alkylating damage and regulate the expression of
      brc1+ in response to MMS. Set2 also show epistasis with DNA damage checkpoint
      proteins; regulates the activation of Chk1, a DNA damage response effector
      kinase; and acts in a similar functional group as proteins involved in homologous
      recombination. Consistently, Set2 and H3K36 ensure the dynamicity of Rhp54 in DNA
      repair foci formation after MMS treatment. Overall, our results indicate a novel
      role for Set2/H3K36me in coordinating the recruitment of DNA repair machineries
      to timely manage alkylating damage.

PMID- 29635345
TI  - Bis-Indole-Derived NR4A1 Ligands and Metformin Exhibit NR4A1-Dependent Glucose
      Metabolism and Uptake in C2C12 Cells.
AB  - Treatment of C2C12 muscle cells with metformin or the NR4A1 ligand 1,1-bis(3'
      indolyl)-1-(p-hydroxyphenyl)methane (DIM-C-pPhOH) induced NR4A1 and Glut4
      messenger RNA and protein expression. Similar results were observed with
      buttressed (3- or 3,5-substituted) analogs of DIM-C-pPhOH, including 1,1-bis(3'
      indolyl)-1-(3-chloro-4-hydroxy-5-methoxyphenyl)methane (DIM-C-pPhOH-3-Cl-5-OCH3),
      and the buttressed analogs were more potent than DIM-C-pPhOH NR4A1 agonists.
      Metformin and the bis-indole substituted analogs also induced expression of
      several glycolytic genes and Rab4, which has previously been linked to enhancing
      cell membrane accumulation of Glut4 and overall glucose uptake in C2C12 cells,
      and these responses were also observed after treatment with metformin and the
      NR4A1 ligands. The role of NR4A1 in mediating the responses induced by the bis
      indoles and metformin was determined by knockdown of NR4A1, and this resulted in
      attenuating the gene and protein expression and enhanced glucose uptake responses
      induced by these compounds. Our results demonstrate that the bis-indole-derived
      NR4A1 ligands represent a class of drugs that enhance glucose uptake in C2C12
      muscle cells, and we also show that the effects of metformin in this cell line
      are NR4A1-dependent.

PMID- 29635347
TI  - Erratum for Bahadoran et al. The nitrate-independent blood pressure-lowering
      effect of beetroot juice: a systematic review and meta-analysis. Adv Nutr
      2017;8(6):830-8.

PMID- 29635346
TI  - Early life thermal stress: Impact on future thermotolerance, stress response,
      behavior, and intestinal morphology in piglets exposed to a heat stress challenge
      during simulated transport.
AB  - Study objectives were to evaluate the impact of early life thermal stress (ELTS)
      on thermoregulation, stress response, and intestinal health of piglets subjected
      to a future heat stress (HS) challenge during simulated transport. From d 7 to 9
      post-farrowing, 12 first-parity sows and their litters were exposed to
      thermoneutral (ELTN; 25.4 +/- 1.1  degrees C w/heat lamp; n = 4), HS (ELHS;
      cycling 32-38  degrees C w/heat lamp; n = 4), or cold stress (ELCS; 25.4 +/- 1.1 
      degrees C w/no heat lamp; n = 4) conditions, and then from d 10 until weaning all
      piglets were exposed to thermoneutral (TN) conditions (25.3 +/- 1.9  degrees C
      w/heat lamp). During the ELTS period, respiration rate, rectal temperature (TR),
      and skin temperature (TS) of three mixed-sex piglets per dam were monitored daily
      (0800, 1200, 1600, 2000 h). At 13 +/- 1.3 d of age, temperature recorders were
      implanted intra-abdominally into all piglets. At weaning (20.0 +/- 1.3 d of age),
      piglets were bled and then herded up a ramp into a simulated transport trailer
      and exposed to HS conditions (cycling 32-38  degrees C) for 8 h. During the 8 h
      simulated transport, core body temperature (TC) and TS were assessed every 15
      min. After the simulated transport, piglets were unloaded from the trailer, bled,
      weighed, and then housed individually in TN conditions (28.5 +/- 0.7  degrees C)
      for 7 d. During this time, ADFI and ADG were monitored, blood samples were taken
      on d 1, 4, and 7, and piglets were video-recorded to assess behavior. Piglets
      were sacrificed on d 8 post-simulated transport and intestinal morphology was
      assessed. Data were analyzed using PROC MIXED in SAS 9.4. In the ELTS period,
      piglet TR was increased overall (P = 0.01) in ELHS (39.77 +/- 0.05  degrees C)
      compared to ELTN (39.34 +/- 0.05  degrees C) and ELCS (39.40 +/- 0.05  degrees C)
      litters. During simulated transport, TC was greater (P = 0.02) in ELHS (40.84 +/-
      0.12  degrees C) compared to ELTN (40.49 +/- 0.12  degrees C) and ELCS (40.39 +/-
      0.12  degrees C) pigs. Following simulated transport, BW loss was greater (P =
      0.01; 40%) for ELHS compared to ELTN and ELCS pigs and ADFI was reduced (P =
      0.05; 28.6%) in ELHS compared to ELTN pigs. Sitting behavior tended to be
      increased (P = 0.06; 47.4%) in ELHS vs. ELCS or ELTN pigs. Overall, circulating
      cortisol was greater for ELHS (P <= 0.01; 38.8%) compared to ELCS and ELTN pigs.
      Goblet cells per villi were reduced (P = 0.02; 20%) in the jejunum of ELHS vs.
      ELCS and ELTN pigs. In summary, ELHS reduced thermotolerance and increased the
      future stress response of piglets compared to ELCS and ELTN.

PMID- 29635348
TI  - Force Modulating Tissue Bridges for Reduction of Tension and Scar: Finite Element
      and Image Analysis of Preclinical Incisional and Nonincisional Models.
AB  - Background: Force modulating tissue bridges (FMTB) represent a new class of
      combined wound closure and scar reduction device designed to optimize the tension
      milieu of the healing wound. Objectives: Engineering analysis and testing in both
      intact skin and incisional models was undertaken to assess changes in tissue
      tension associated with device placement and compare to standard suture closure.
      Methods: Nonlinear, large deformation finite element analyses (FEA) were
      performed to compare the strains applied to tissues with sutures and FMTB. In the
      incisional model, a freshly euthanized Yorkshire pig received full thickness
      cutaneous incisions followed by alternating closure with sutures and FMTBs. FMTBs
      were also applied to intact adult human skin after pattern application. In each
      of the experiments, photographs were taken preapplication and postapplication and
      the resultant dot grid pattern changes were analyzed by image recognition
      algorithms to calculate applied strains. Results: FEA indicate compressive
      stresses at the tissue:suture interface on the order of 4000 mmHg and 20 mmHg at
      the tissue:FMTB interface. Strain analysis of the sutures and FMTBs applied in
      the incisional lab testing indicated imposed strains on the tissues of around
      40%, with FMTBs providing 10% more compression than sutures and 25% more
      compression between the applied devices (P = 0.000057). In the longitudinal
      study, tension reduction of the order of 30% was maintained over the treatment
      period of 10 days to verify device efficacy. Conclusions: FMTBs provide wounds
      while simultaneously modulating skin tension and thus have the potential to
      improve scar appearance.

PMID- 29635349
TI  - Linking inflammation and cancer: the unexpected SYK world.

PMID- 29635352
TI  - Improving Estimation of HIV Viral Suppression in the United States: A Method to
      Adjust HIV Surveillance Estimates From the Medical Monitoring Project Using
      Cohort Data.
AB  - The US Centers for Disease Control and Prevention has estimated human
      immunodeficiency virus (HIV) viral suppression (VS) using 2 data sources. The
      National HIV Surveillance System estimate (50% of HIV-diagnosed persons in 2012)
      is derived from viral load reporting from a subset of jurisdictions that vary
      yearly. The Medical Monitoring Project (MMP) estimate (42% of HIV-diagnosed
      persons in 2012) is based on a sample of persons receiving HIV care during the
      first 4 months of each year. We developed the cohort-adjustment method to
      reconstruct VS estimates, accounting for persons receiving care later in the
      year. Using the HIV Outpatient Study cohort, we assessed timing of care receipt,
      demographics, and VS at last test (<200 vs. >=200 copies/mL), standardizing MMP
      to HIV Outpatient Study data using multivariable regression models and yielding
      adjusted VS estimates. We estimated that 52% (95% CI: 48, 56) of HIV-diagnosed
      persons achieved VS in 2012. Differences from previously published estimates were
      due to: 1) 23% underestimation of persons receiving HIV care, and 2) lower VS
      rates among persons receiving care outside versus inside the 4-month MMP sampling
      period (79% vs. 88%). This methodology yielded VS estimates closer to the
      National HIV Surveillance System estimate than previously published. Use of more,
      geographically diverse cohort data may enable assessment of temporal trends.

PMID- 29635351
TI  - Inequality signals in dorsolateral prefrontal cortex inform social preference
      models.
AB  - Humans typically display inequality aversion in social situations, which
      manifests itself as a preference for fairer distributions of resources. However,
      people differ in the degree to which they dislike being worse off
      [disadvantageous inequality (DI) aversion] or better off [advantageous inequality
      (AI) aversion] than others. Competing models explain such behavior by focusing on
      aversion to payoff differences, maximization of total payoff or reciprocity.
      Using functional near-infrared spectroscopy, we asked which of these theories
      could better explain dorsolateral prefrontal cortex (dlPFC) activity while
      participants accepted or punished fair vs unfair monetary transfers in an
      anonymous norm compliance task. We found that while all participants exhibited DI
      aversion, there were substantial differences in preferences for AI, which were
      strongly predicted by dlPFC activation. Model comparisons revealed that both
      punishment behavior and prefrontal activity were best explained by a model that
      allowed for AI seeking rather than imposing aversion. Moreover, enhancing this
      model by taking into account behavioral response times, as a proxy for choice
      difficulty, further improved model fits. Our data provide evidence that the dlPFC
      encodes subjective values of payoff inequality and that this representation is
      richer than envisaged by standard models of social preferences.

PMID- 29635353
TI  - The relation of age at menarche with age at natural menopause: a population study
      of 336 788 women in Norway.
AB  - STUDY QUESTION: Is age at menarche associated with age at menopause or with
      duration of the reproductive period (interval between menarche and menopause)?
      SUMMARY ANSWER: The association of age at menarche with age at menopause was weak
      and non-linear, and the duration of the reproductive period decreased by
      increasing age at menarche. WHAT IS KNOWN ALREADY: It remains uncertain whether
      age at menarche is associated with age at menopause. Some studies report that
      women with early menarche also have early menopause. Other studies report that
      women with early menarche have late menopause, or they report no association. The
      duration of the reproductive period may be an indicator of the cumulative
      endogenous exposure to estrogens and progestogens during life course and is
      associated with risk of breast cancer and endometrial cancer. STUDY DESIGN, SIZE,
      DURATION: A retrospective cohort study of 336 788 women, aged 48-71 years, in the
      BreastScreen Norway during the years 2006-2014 was performed.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: Information about age at menarche and
      menopausal status was obtained by self-administered questionnaires. We used time
      to event approaches to estimate the associations. MAIN RESULTS AND THE ROLE OF
      CHANCE: Median age at menopause was 51 years in most menarche groups. Women with
      menarche at age 16 years or age >= 17 years had menopause 1 year later [median:
      52 years, interquartile range (IQR): 49-54 years] than women with menarche at age
      13 years (median: 51 years, IQR: 49-54 years, reference) (crude hazard ratio (HR)
      = 0.95; 95% CI: 0.93-0.97 and 0.95; 95% CI: 0.92-0.99, Pnon-linearity < 0.001).
      The reproductive period decreased with increasing age at menarche (Pnon-linearity
      < 0.001), and women with menarche at age <= 9 years had 9 years longer median
      reproductive period than women with menarche at age >= 17 years (median: 43
      versus 34 years). Adjustment for year of birth did not change the HR estimates
      notably. LARGE SCALE DATA: Not applicable. LIMITATIONS, REASONS FOR CAUTION:
      Information about age at menarche and age at menopause was based on self-reports.
      Particularly for age at menarche, the long time interval between the event and
      data collection may have caused imprecise reporting. WIDER IMPLICATIONS OF THE
      FINDINGS: Our study suggests that age at menarche is a strong indicator for the
      duration of women's reproductive period. Our findings should encourage studies of
      the independent role of duration of the reproductive period on the risk of breast
      cancer and endometrial cancer, since these cancers have been associated with
      exposure to estrogens and progestogens. STUDY FUNDING/COMPETING INTEREST(S): The
      present study was funded by the Norwegian Cancer Society [Grant number 6863294
      2015]. The authors declare no conflicts of interest.

PMID- 29635354
TI  - The SlFSR gene controls fruit shelf-life in tomato.
AB  - Fruit ripening represents a process that changes flavor and appearance and also a
      process that dramatically increases fruit softening. Fruit softening and textural
      variations mainly result from disruptions to the cell walls of the fruit
      throughout ripening, but the exact mechanisms and specific modifications of the
      cell wall remain unclear. Plant-specific GRAS proteins play a critical role in
      development and growth. To date, few GRAS genes have been functionally
      categorized in tomato. The expression of a novel GRAS gene described in this
      study and designated as SlFSR (fruit shelf-life regulator) specifically increased
      during fruit ripening, but was significantly decreased in the tomato mutant rin
      (ripening inhibitor). RNAi repression of SlFSR resulted in reduced expression of
      multiple cell wall modification-related genes, decreased the activities of PG
      (polygalacturonase), TBG (tomato beta-galactosidase), CEL (cellulase), and XYL
      (beta-D-xylosidase), and significantly prolonged fruit shelf-life. Furthermore,
      overexpression of SlFSR in mutant rin gave rise to up-regulated expression of
      multiple cell wall modification-related genes, such as PG, TBG4, CEL2, XYL1, PL,
      PE, MAN1, EXP1, and XTH5, and significantly shortened the fruit shelf-life. These
      findings reveal some of the genetic mechanisms underlying fruit cell wall
      metabolism and suggest that the SlFSR gene is another potential biotechnological
      target for the control of tomato fruit shelf-life.

PMID- 29635355
TI  - Paul Hugenholtz MD at 90.

PMID- 29635356
TI  - Carlos E Ruiz.

PMID- 29635357
TI  - Neglected Populations, Neglected Diseases.

PMID- 29635358
TI  - German Cardiac Society: Its History.

PMID- 29635359
TI  - VSClust: feature-based variance-sensitive clustering of omics data.
AB  - Motivation: Data clustering is indispensable for identifying biologically
      relevant molecular features in large-scale omics experiments with thousands of
      measurements at multiple conditions. Optimal clustering results yield groups of
      functionally related features that may include genes, proteins and metabolites in
      biological processes and molecular networks. Omics experiments typically include
      replicated measurements of each feature within a given condition to statistically
      assess feature-specific variation. Current clustering approaches ignore this
      variation by averaging, which often leads to incorrect cluster assignments.
      Results: We present VSClust that accounts for feature-specific variance. Based on
      an algorithm derived from fuzzy clustering, VSClust unifies statistical testing
      with pattern recognition to cluster the data into feature groups that more
      accurately reflect the underlying molecular and functional behavior. We apply
      VSClust to artificial and experimental datasets comprising hundreds to >80 000
      features across 6-20 different conditions including genomics, transcriptomics,
      proteomics and metabolomics experiments. VSClust avoids arbitrary averaging
      methods, outperforms standard fuzzy c-means clustering and simplifies the data
      analysis workflow in large-scale omics studies. Availability and implementation:
      Download VSClust at https://bitbucket.org/veitveit/vsclust or access it through
      computproteomics.bmb.sdu.dk/Apps/VSClust. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 29635360
TI  - Longitudinal Assessment of Multidrug-Resistant Organisms in Newly Admitted
      Nursing Facility Patients: Implications for an Evolving Population.
AB  - Background: The spread of multidrug-resistant organisms (MDROs) is a global
      concern, and much about transmission in healthcare systems remains unknown. To
      reduce hospital stays, nursing facilities (NFs) have increasingly assumed care of
      post-acute populations. We estimate the prevalence of MDRO colonization in NF
      patients on enrollment and discharge to community settings, risk factors for
      colonization, and rates of acquiring MDROs during the stay. Methods: We conducted
      a prospective, longitudinal cohort study of newly admitted patients in 6 NFs in
      southeast Michigan using active microbial surveillance of multiple anatomic sites
      sampled at enrollment, days 14 and 30, and monthly thereafter for up to 6 months.
      Results: We enrolled 651 patients and collected 7526 samples over 1629 visits,
      with an average of 29 days of follow-up per participant. Nearly all participants
      were admitted for post-acute care (95%). More than half (56.8%) were colonized
      with MDROs at enrollment: methicillin-resistant Staphylococcus aureus (MRSA),
      16.1%; vancomycin-resistant enterococci (VRE), 33.2%; and resistant gram-negative
      bacilli (R-GNB), 32.0%. Risk factors for colonization at enrollment included
      prolonged hospitalization (>14 days), functional disability, antibiotic use, or
      device use. Rates per 1000 patient-days of acquiring a new MDRO were MRSA, 3.4;
      VRE, 8.2; and R-GNB, 13.6. MDRO colonization at discharge was similar to that at
      enrollment (56.4%): MRSA, 18.4%; VRE, 30.3%; and R-GNB, 33.6%. Conclusions: Short
      stay NF patients exhibit a high prevalence of MDROs near the time of admission,
      as well as at discharge, and may serve as a reservoir for spread in other
      healthcare settings. Future interventions to reduce MDROs should specifically
      target this population.

PMID- 29635361
TI  - Central IKK2 Inhibition Ameliorates Air Pollution-Mediated Hepatic Glucose and
      Lipid Metabolism Dysfunction in Mice With Type II Diabetes.
AB  - Previous studies supported a role of hypothalamic inflammation in fine ambient
      particulate matter (PM2.5) exposure-mediated diabetes development. We therefore
      investigated the effects of PM2.5 exposure on insulin resistance and the
      disorders of hepatic glucose and lipid metabolism via hypothalamic inflammation.
      KKAy mice, a genetically susceptible model of type II diabetes mellitus, were
      administered intra-cerebroventricularly with IKK2 inhibitor (IMD-0354) and were
      exposed to either concentrated PM2.5 or filtered air (FA) for 4 weeks
      simultaneously via a versatile aerosol concentration exposure system. At the end
      of the exposure, fasting blood glucose and serum insulin were evaluated before
      epididymal adipose tissue and liver were collected, flow cytometry, quantitative
      PCR and Western blot were performed at euthanasia. We observed that
      intracerebroventricular administration of IMD-0354 attenuated insulin resistance,
      inhibited macrophage polarization to M1 phenotype in epididymal adipose tissue in
      response to PM2.5 exposure. Although the treatment did not affect hepatic
      inflammation or endoplasmic reticulum stress, it inhibited the expression of the
      enzymes for gluconeogenesis and lipogenesis in the liver. Therefore, our current
      finding indicates an important role of hypothalamic inflammation in PM2.5
      exposure-mediated hepatic glucose and lipid metabolism disorder.

PMID- 29635362
TI  - Using clinician text notes in electronic medical record data to validate
      transgender-related diagnosis codes.
AB  - Objective: Transgender individuals are vulnerable to negative health risks and
      outcomes, but research remains limited because data sources, such as electronic
      medical records (EMRs), lack standardized collection of gender identity
      information. Most EMR do not include the gold standard of self-identified gender
      identity, but International Classification of Diseases (ICDs) includes diagnostic
      codes indicating transgender-related clinical services. However, it is unclear if
      these codes can indicate transgender status. The objective of this study was to
      determine the extent to which patients' clinician notes in EMR contained
      transgender-related terms that could corroborate ICD-coded transgender identity.
      Methods: Data are from the US Department of Veterans Affairs Corporate Data
      Warehouse. Transgender patients were defined by the presence of ICD9 and ICD10
      codes associated with transgender-related clinical services, and a 3:1 comparison
      group of nontransgender patients was drawn. Patients' clinician text notes were
      extracted and searched for transgender-related words and phrases. Results: Among
      7560 patients defined as transgender based on ICD codes, the search algorithm
      identified 6753 (89.3%) with transgender-related terms. Among 22 072 patients
      defined as nontransgender without ICD codes, 246 (1.1%) had transgender-related
      terms; after review, 11 patients were identified as transgender, suggesting a
      0.05% false negative rate. Conclusions: Using ICD-defined transgender status can
      facilitate health services research when self-identified gender identity data are
      not available in EMR.

PMID- 29635363
TI  - Sprouty2 enhances the tumorigenic potential of glioblastoma cells.
AB  - Background: Sprouty2 (SPRY2), a feedback regulator of receptor tyrosine kinase
      (RTK) signaling, has been shown to be associated with drug resistance and cell
      proliferation in glioblastoma (GBM), but the underlying mechanisms are still
      poorly defined. Methods: SPRY2 expression and survival patterns of patients with
      gliomas were analyzed using publicly available databases. Effects of RNA
      interference targeting SPRY2 on cellular proliferation in established GBM or
      patient-derived GBM stemlike cells were examined. Loss- or gain-of-function of
      SPRY2 to regulate the tumorigenic capacity was assessed in both intracranial and
      subcutaneous xenografts. Results: SPRY2 was found to be upregulated in GBM, which
      correlated with reduced survival in GBM patients. SPRY2 knockdown significantly
      impaired proliferation of GBM cells but not of normal astrocytes. Silencing of
      SPRY2 increased epidermal growth factor-induced extracellular signal-regulated
      kinase (ERK) and Akt activation causing premature onset of DNA replication,
      increased DNA damage, and impaired proliferation, suggesting that SPRY2
      suppresses DNA replication stress. Abrogating SPRY2 function strongly inhibited
      intracranial tumor growth and led to significantly prolonged survival of U87
      xenograft-bearing mice. In contrast, SPRY2 overexpression promoted tumor
      propagation of low-tumorigenic U251 cells. Conclusions: The present study
      highlights an antitumoral effect of SPRY2 inhibition that is based on excessive
      activation of ERK signaling and DNA damage response, resulting in reduced cell
      proliferation and increased cytotoxicity, proposing SPRY2 as a promising
      pharmacological target in GBM patients.

PMID- 29635365
TI  - Complete Genome Sequences of Seven Vibrio anguillarum Strains as Derived from
      PacBio Sequencing.
AB  - We report here the complete genome sequences of seven Vibrio anguillarum strains
      isolated from multiple geographic locations, thus increasing the total number of
      genomes of finished quality to 11. The genomes were de novo assembled from long
      sequence PacBio reads. Including draft genomes, a total of 44 V. anguillarum
      genomes are currently available in the genome databases. They represent an
      important resource in the study of, for example, genetic variations and for
      identifying virulence determinants. In this article, we present the genomes and
      basic genome comparisons of the 11 complete genomes, including a BRIG analysis,
      and pan genome calculation. We also describe some structural features of
      superintegrons on chromosome 2 s, and associated insertion sequence (IS)
      elements, including 18 new ISs (ISVa3 - ISVa20), both of importance in the
      complement of V. anguillarum genomes.

PMID- 29635366
TI  - Thermal Performance of Two Indigenous Pupal Parasitoids Attacking the Invasive
      Drosophila suzukii (Diptera: Drosophilidae).
AB  - Pachycrepoideus vindemiae (Rondani) and Trichopria drosophilae (Perkins) are
      among a few indigenous parasitoids attacking the invasive Drosophila suzukii
      (Matsumura) (Diptera: Drosophilidae) in North America. Both parasitoid species
      occur in California, whereas only P. vindemiae has been reported from Oregon. We
      compared the thermal performance of the California populations of P. vindemiae
      and T. drosophilae, and the Oregon population of P. vindemiae at eight constant
      temperatures (12.6-32.8 degrees C). Both P. vindemiae populations could develop
      at all tested temperatures. T. drosophilae failed to develop at or above 29.6
      degrees C. This species was, however, able to develop at a diurnal temperature
      regime of 15-32 degrees C, and survival was higher in older developmental stages.
      T. drosophilae was less tolerant to both low and high temperatures than P.
      vindemiae, whereas the Oregon P. vindemiae population was more cold-tolerant but
      less heat-tolerant than the California population in terms of offspring survival,
      development, and reproduction. To develop storage strategies for mass-cultured
      parasitoids, we compared the cold tolerance of immature P. vindemiae and T.
      drosophilae of the California populations at 12 degrees C for 1, 2, or 3 mo,
      followed by a 23 degrees C holding period. Successful development to the adult
      stage decreased as cold storage duration increased. Successful development,
      however, increased when cold storage was initiated during the older developmental
      stages for 1-mo exposure for both parasitoid species. The results are discussed
      with regards to parasitoid thermal adaptation and the potential use of P.
      vindemiae and T. drosophilae for biological control of spotted-wing drosophila.

PMID- 29635364
TI  - MIR137 schizophrenia-associated locus controls synaptic function by regulating
      synaptogenesis, synapse maturation and synaptic transmission.
AB  - The MIR137 locus is a replicated genetic risk factor for schizophrenia. The risk
      associated allele is reported to increase miR-137 expression and miR-137
      overexpression alters synaptic transmission in mouse hippocampus. We investigated
      the cellular mechanisms underlying these observed effects in mouse hippocampal
      neurons in culture. First, we correlated the risk allele to expression of the
      genes in the MIR137 locus in human postmortem brain. Some evidence for increased
      MIR137HG expression was observed, especially in hippocampus of the disease
      associated genotype. Second, in mouse hippocampal neurons, we confirmed
      previously observed changes in synaptic transmission upon miR-137 overexpression.
      Evoked synaptic transmission and spontaneous release were 50% reduced. We
      identified defects in release probability as the underlying cause. In contrast to
      previous observations, no evidence was obtained for selective synaptic vesicle
      docking defects. Instead, ultrastructural morphometry revealed multiple effects
      of miR-137 overexpression on docking, active zone length and total vesicle
      number. Moreover, proteomic analyses of neuronal protein showed that expression
      of Syt1 and Cplx1, previously reported as downregulated upon miR-137
      overexpression, was unaltered. Immunocytochemistry of synapses overexpressing miR
      137 showed normal Synaptotagmin1 and Complexin1 protein levels. Instead, our
      proteomic analyses revealed altered expression of genes involved in
      synaptogenesis. Concomitantly, synaptogenesis assays revealed 31% reduction in
      synapse formation. Taken together, these data show that miR-137 regulates
      synaptic function by regulating synaptogenesis, synaptic ultrastructure and
      synapse function. These effects are plausible contributors to the increased
      schizophrenia risk associated with miR-137 overexpression.

PMID- 29635368
TI  - DNA Barcodes for Forensically Important Fly Species in Brazil.
AB  - Here, we analyze 248 DNA barcode sequences of 35 fly species of forensic
      importance in Brazil. DNA barcoding can be effectively used for specimen
      identification of these species, allowing the unambiguous identification of 31
      species, an overall success rate of 88%. Our results show a high rate of success
      for molecular identification using DNA barcoding sequences and open new
      perspectives for immature species identification, a subject on which limited
      forensic investigations exist in Tropical regions. We also address the
      implications of building a robust forensic DNA barcode database. A geographic
      bias is recognized for the COI dataset available for forensically important fly
      species in Brazil, with concentration of sequences from specimens collected
      mainly in sites located in the Cerrado, Mata Atlantica, and Pampa biomes.

PMID- 29635367
TI  - First nationwide antimicrobial susceptibility surveillance for Neisseria
      gonorrhoeae in Brazil, 2015-16.
AB  - Objectives: Gonorrhoea and antimicrobial resistance (AMR) in Neisseria
      gonorrhoeae are major public health concerns globally. Enhanced AMR surveillance
      for gonococci is essential worldwide; however, recent quality-assured gonococcal
      AMR surveillance in Latin America, including Brazil, has been limited. Our aims
      were to (i) establish the first nationwide gonococcal AMR surveillance, quality
      assured according to WHO standards, in Brazil, and (ii) describe the
      antimicrobial susceptibility of clinical gonococcal isolates collected from 2015
      to 2016 in all five main regions (seven sentinel sites) of Brazil. Methods:
      Gonococcal isolates from 550 men with urethral discharge were examined for
      susceptibility to ceftriaxone, cefixime, azithromycin, ciprofloxacin,
      benzylpenicillin and tetracycline using the agar dilution method, according to
      CLSI recommendations and quality assured according to WHO standards. Results: The
      levels of resistance (intermediate susceptibility) to tetracycline,
      ciprofloxacin, benzylpenicillin and azithromycin were 61.6% (34.2%), 55.6%
      (0.5%), 37.1% (60.4%) and 6.9% (8.9%), respectively. All isolates were
      susceptible to ceftriaxone and cefixime using the US CLSI breakpoints. However,
      according to the European EUCAST cefixime breakpoints, 0.2% (n = 1) of isolates
      were cefixime resistant and 6.9% (n = 38) of isolates had a cefixime MIC
      bordering on resistance. Conclusions: This study describes the first national
      surveillance of gonococcal AMR in Brazil, which was quality assured according to
      WHO standards. The high resistance to ciprofloxacin (which promptly informed a
      revision of the Brazilian sexually transmitted infection treatment guideline),
      emerging resistance to azithromycin and decreasing susceptibility to extended
      spectrum cephalosporins necessitate continuous surveillance of gonococcal AMR and
      ideally treatment failures, and increased awareness when prescribing treatment in
      Brazil.

PMID- 29635369
TI  - Proteomic Comparison of Various Hepatic Cell Cultures for Preclinical Safety
      Pharmacology.
AB  - Experimental drugs need to be screened for safety within time constraints.
      Hepatotoxicity is one concerning contributor to the failure of investigational
      new drugs and a major rationale for postmarketing withdrawal decisions. Ethical
      considerations in preclinical research force the requirement for highly
      predictive in vitro assays using human tissue which retains functionality
      reflective of primary tissue. Here, the proteome of cells commonly used to assess
      preclinical hepatotoxicity was compared. Primary human hepatocytes (PHHs),
      hepatocyte-like cells (HLCs) differentiated from human pluripotent stem cells,
      HepG2 cell monolayers and HepG2 cell 3D spheroids were cultured and collected as
      whole cell lysates. Over 6000 proteins were identified and quantified in terms of
      relative abundance in replicate proteomic experiments using isobaric tagging
      methods. Comparison of these quantitative data provides biological insight into
      the feasibility of using HLCs, HepG2 monolayers, and HepG2 3D spheroids for
      hepatotoxicity testing. Collectively these data reveal how HLCs differentiated
      for 35 days and HepG2 cells proteomes differ from one another and that of PHHs.
      HepG2 cells possess a strong cancer cell signature and do not adequately express
      key metabolic proteins which mark the hepatic phenotype, this was not
      substantially altered by culturing as 3D spheroids. These data suggest that while
      no single hepatic model reflects the diverse array of outcomes required to mimic
      the in vivo liver functions, that HLCs are the most suitable investigational
      avenue for replacing PHHs in vitro.

PMID- 29635370
TI  - The health of Antillean migrants in the Netherlands: a comparison with the health
      of non-migrants in both the countries of origin and destination.
AB  - Background: This article examines risk factor and health differences between
      Antillean migrants in the Netherlands and Antillean and Dutch non-migrants, and
      relates these findings to four commonly used explanations for migrant health
      disparities. Methods: Nationally representative data from the 2012 Dutch Public
      Health Monitor and the 2013 National Health Survey Curacao was used. The weighted
      rates were calculated and significance assessed using the chi2 test. Logistic
      regression analyses were used to compare health behaviours and outcomes between
      Antillean migrants and the non-migrant populations. Results: Overall, Antillean
      migrants had poorer physical and mental health than Antillean and Dutch non
      migrants. For overweight/obesity and tobacco and alcohol use, Antillean migrants
      had rates in-between those of the Antillean and Dutch non-migrants. The poor
      health of Antillean migrants persisted in the second generation, who were born in
      the Netherlands. Conclusions: Patterns of differences in physical and mental
      health among the study populations were suggestive of a 'stressful environment'
      effect. The poorer health of Antillean migrants may be partly determined by host
      country-specific stressors, such as perceived discrimination, spatial
      concentration in multi-ethnic neighbourhoods and reduced social mobility.

PMID- 29635371
TI  - Two-step transplantation with adipose tissue-derived stem cells increases
      follicle survival by enhancing vascularization in xenografted frozen-thawed human
      ovarian tissue.
AB  - STUDY QUESTION: Do adipose tissue-derived stem cells (ASCs) enhance
      vascularization and follicle survival in xenografted ovarian tissue using a two
      step transplantation approach? SUMMARY ANSWER: Higher rates of oxygenation and
      vascularization of ovarian tissue, as well as increased follicle survival rates,
      were detected in the early post-grafting period. WHAT IS KNOWN ALREADY: ASCs have
      multilineage differentiation potential, proangiogenic properties and enhance
      vascularization in a peritoneal grafting site. Some studies suggest that using
      ASCs may improve ovarian tissue quality by enhancing graft angiogenesis. STUDY
      DESIGN, SIZE, DURATION: A total of 15 severe combined immunodeficient (SCID) mice
      were intraperitoneally grafted with frozen-thawed human ovarian tissue (OT) from
      five different patients. A peritoneal transplantation site had been previously
      prepared in a first step using either empty fibrin (Fi+OT group [n = 5]) or ASC
      loaded fibrin (Fi/ASCs+OT group [n = 5]) for 14 days prior to grafting. Five mice
      underwent the standard one-step transplantation procedure and served as controls
      (OT group). Lithium phthalocyanine (LiPc) crystals were inserted into all grafted
      human ovarian tissue before transplantation. Levels of partial pressure of oxygen
      (pO2) in grafts were monitored in vivo by electron paramagnetic resonance (EPR)
      oximetry on Days 3 and 7. Samples for histology and immunohistochemistry (IHC)
      were collected after euthanizing the mice on Day 7 following EPR. One piece of
      ovarian tissue per patient was fixed for analysis to serve as non-grafted
      controls. PARTICIPANTS/MATERIALS, SETTING, METHODS: Prospective experimental
      study conducted at the Gynecology Research Unit, Universite Catholique de
      Louvain. All materials were used to perform pO2 measurements (EPR oximetry),
      histological (haematoxylin and eosin staining), immunohistochemistry (anti-mouse
      and human double CD34 and anti-human Ki-67) and TUNEL analyses. MAIN RESULTS AND
      THE ROLE OF CHANCE: A significant increase in pO2 was observed in all groups
      between Days 3 and 7 (P < 0.001). A significantly higher pO2 level was observed
      in the Fi/ASCs+OT group compared to the OT group on Day 7 (P = 0.028). Total CD34
      positive vessel area on Day 7 was greater in the Fi/ASCs+OT group than in any
      other group (vs non-grafted group: P = 0.0014; vs OT group: P = 0.013; vs Fi+OT
      group: P = 0.018). Primordial follicle survival rates after grafting were higher
      in the Fi/ASCs+OT group than in the OT (P = 0.0059) or Fi+OT groups (P = 0.0307).
      TUNEL-positive follicle percentages after grafting were significantly lower in
      the Fi/ASCs+OT group than in any other grafted tissue (vs OT group: P = 0.045; vs
      Fi+OT group: P = 0.0268). Percentages of Ki-67-positive primordial follicles were
      significantly higher in all grafted groups compared to non-grafted tissue
      controls (P < 0.01). LIMITATIONS REASONS FOR CAUTION: As demonstrated by our
      results, the proposed two-step ovarian tissue transplantation procedure using
      ASCs enhances vascularization in the early post-grafting period, leading to
      increased follicle survival rates and decreased apoptosis. However, mechanisms
      involved in the proangiogenic behavior of ASCs remain to be elucidated. WIDER
      IMPLICATIONS OF THE FINDINGS: Our results suggest that the proposed
      transplantation procedure with ASCs is a promising step towards potentially
      solving the problem of massive follicle loss after ovarian tissue grafting. STUDY
      FUNDING/COMPETING INTEREST(S): This study was supported by grants from the Fonds
      National de la Recherche Scientifique de Belgique (FNRS-PDR Convention T.0077.14,
      grant Televie No. 7.6515.16 F to DDM and grant 5/4/150/5 awarded to MMD and CAA
      is research associate, FRS-FNRS), Fonds Speciaux de Recherche, Fondation St Luc,
      and Foundation Against Cancer, and donations from the Ferrero family.

PMID- 29635372
TI  - Genome Sequences of Apibacter spp., Gut Symbionts of Asian Honey Bees.
AB  - Honey bees have distinct gut microbiomes consisting almost entirely of several
      host-specific bacterial species. We present the genomes of three strains of
      Apibacter spp., bacteria of the Bacteroidetes phylum that are endemic to Asian
      honey bee species (Apis dorsata and Apis cerana). The Apibacter strains have
      similar metabolic abilities to each other and to Apibacter mensalis, a species
      isolated from a bumble bee. They use microaerobic respiration and fermentation to
      catabolize a limited set of monosaccharides and dicarboxylic acids. All strains
      are capable of gliding motility and encode a type IX secretion system. Two
      strains and A. mensalis have type VI secretion systems, and all strains encode
      Rhs or VgrG proteins used in intercellular interactions. The characteristics of
      Apibacter spp. are consistent with adaptions to life in a gut environment;
      however, the factors responsible for host-specificity and mutualistic
      interactions remain to be uncovered.

PMID- 29635373
TI  - Structural dynamics of the N-terminal domain and the Switch loop of Prp8 during
      spliceosome assembly and activation.
AB  - Precursor message RNA (pre-mRNA) splicing is executed by the spliceosome, a large
      ribonucleoprotein (RNP) machinery that is comparable to the ribosome. Driven by
      the rapid progress of cryo-electron microscopy (cryo-EM) technology, high
      resolution structures of the spliceosome in its different splicing stages have
      proliferated over the past three years, which has greatly facilitated the
      mechanistic understanding of pre-mRNA splicing. As the largest and most conserved
      protein in the spliceosome, Prp8 plays a pivotal role within this protein
      directed ribozyme. Structure determination of different spliceosomal complexes
      has revealed intimate and dynamic interactions between Prp8 and catalytic RNAs as
      well as with other protein factors during splicing. Here we review the structural
      dynamics of two elements of Prp8, the N-terminal domain (N-domain) and the Switch
      loop, and delineate the dynamic organisation and underlying functional
      significance of these two elements during spliceosome assembly and activation.
      Further biochemical and structural dissections of idiographic splicing stages are
      much needed for a complete understanding of the spliceosome and pre-mRNA
      splicing.

PMID- 29635375
TI  - Patterns of radiotherapy infrastructure in Japan and in other countries with well
      developed radiotherapy infrastructures.
AB  - Background: In high-income countries, the number of radiotherapy machine per
      population reaches a sufficient level. However, the patterns of infrastructure of
      radiotherapy in high-income countries are not well known. Methods: Among 29 high
      income countries with gross national income of $25,000 or more per capita, we
      selected 23 countries whose total number of newly diagnosed cancer patients in
      2012 was reported in the Organisation for Economic Co-operation and Development
      Health Statistics 2017. The numbers of radiotherapy centers and teletherapy
      machines in each of these 23 countries were collected using the Dictionary of
      Radiotherapy Centers database. Results: The number of cancer patients per
      teletherapy machine was 452.35-1398.22 (median 711.66) with a three-fold
      variation, whereas the number of cancer patients per radiotherapy center varied
      even more widely, from 826.16 to 5159.86 (median 2259.83) with a six-fold
      variation. The average number of teletherapy machines per radiotherapy center
      also ranged widely, from 1.24 to 8.29 (median 3.11) with a seven-fold variation.
      The number of teletherapy machines in each country was almost proportional to
      that of cancer patients, and the number of teletherapy machines per radiotherapy
      center was inversely related to the number of radiotherapy centers per cancer
      patients. The number of teletherapy machines per radiotherapy center in Japan was
      1.24, the most fragmented among the high-income countries. The percentage of
      large radiotherapy centers having three or more teletherapy machines in Japan was
      the smallest among 23 high-income countries. Conclusions: Optimization of the
      radiotherapy infrastructure in Japan should be carefully considered.

PMID- 29635376
TI  - Analysis of the effects of EHR implementation on timeliness of care in a
      dermatology clinic: a simulation study.
AB  - Objective: Quantify the downstream impact on patient wait times and overall
      length of stay due to small increases in encounter times caused by the
      implementation of a new electronic health record (EHR) system. Methods: A
      discrete-event simulation model was created to examine the effects of increasing
      the provider-patient encounter time by 1, 2, 5, or 10 min, due to an increase in
      in-room documentation as part of an EHR implementation. Simulation parameters
      were constructed from an analysis of 52 000 visits from a scheduling database and
      direct observation of 93 randomly selected patients to collect all the steps
      involved in an outpatient dermatology patient care visit. Results: Analysis of
      the simulation results demonstrates that for a clinic session with an average
      booking appointment length of 15 min, the addition of 1, 2, 5, and 10 min for in
      room physician documentation with an EHR system would result in a 5.2 (22%), 9.8
      (41%), 31.8 (136%), and 87.2 (373%) minute increase in average patient wait time,
      and a 6.2 (12%), 11.7 (23%), 36.7 (73%), and 96.9 (193%) minute increase in
      length of stay, respectively. To offset the additional 1, 2, 5, or 10 min,
      patient volume would need to decrease by 10%, 20%, 40%, and >50%, respectively.
      Conclusions: Small changes to processes, such as the addition of a few minutes of
      extra documentation time in the exam room, can cause significant delays in the
      timeliness of patient care. Simulation models can assist in quantifying the
      downstream effects and help analyze the impact of these operational changes.

PMID- 29635374
TI  - Genome-wide determination of on-target and off-target characteristics for RNA
      guided DNA methylation by dCas9 methyltransferases.
AB  - Background: Fusion of DNA methyltransferase domains to the nuclease-deficient
      clustered regularly interspaced short palindromic repeat (CRISPR) associated
      protein 9 (dCas9) has been used for epigenome editing, but the specificities of
      these dCas9 methyltransferases have not been fully investigated. Findings: We
      generated CRISPR-guided DNA methyltransferases by fusing the catalytic domain of
      DNMT3A or DNMT3B to the C terminus of the dCas9 protein from Streptococcus
      pyogenes and validated its on-target and global off-target characteristics. Using
      targeted quantitative bisulfite pyrosequencing, we prove that dCas9-BFP-DNMT3A
      and dCas9-BFP-DNMT3B can efficiently methylate the CpG dinucleotides flanking its
      target sites at different genomic loci (uPA and TGFBR3) in human embryonic kidney
      cells (HEK293T). Furthermore, we conducted whole genome bisulfite sequencing
      (WGBS) to address the specificity of our dCas9 methyltransferases. WGBS revealed
      that although dCas9-BFP-DNMT3A and dCas9-BFP-DNMT3B did not cause global
      methylation changes, a substantial number (more than 1000) of the off-target
      differentially methylated regions (DMRs) were identified. The off-target DMRs,
      which were hypermethylated in cells expressing dCas9 methyltransferase and guide
      RNAs, were predominantly found in promoter regions, 5? untranslated regions, CpG
      islands, and DNase I hypersensitivity sites, whereas unexpected hypomethylated
      off-target DMRs were significantly enriched in repeated sequences. Through
      chromatin immunoprecipitation with massive parallel DNA sequencing analysis, we
      further revealed that these off-target DMRs were weakly correlated with dCas9 off
      target binding sites. Using quantitative polymerase chain reaction, RNA
      sequencing, and fluorescence reporter cells, we also found that dCas9-BFP-DNMT3A
      and dCas9-BFP-DNMT3B can mediate transient inhibition of gene expression, which
      might be caused by dCas9-mediated de novo DNA methylation as well as interference
      with transcription. Conclusion: Our results prove that dCas9 methyltransferases
      cause efficient RNA-guided methylation of specific endogenous CpGs. However,
      there is significant off-target methylation indicating that further improvements
      of the specificity of CRISPR-dCas9 based DNA methylation modifiers are required.

PMID- 29635377
TI  - A Soft Casting Technique for Managing Pediatric Hand and Foot Burns.
AB  - Hand and foot burns in children are difficult to dress. The authors have
      developed a soft casting technique to manage burns to these areas. The aim of
      this study is to report the outcomes using weekly dressing changes with a soft
      casting technique to manage pediatric hand and foot burns in the outpatient
      setting. A retrospective chart review was performed on children with burns to the
      hands or feet, who underwent dressing changes with a soft casting technique at
      the Children's Hospital Colorado Burn Center. Soft casting was performed by
      placing antibiotic ointment-impregnated nonadherent gauze over the burn wound(s),
      wrapping the extremity using rolled gauze, applying soft cast pad, plaster, soft
      cast tape, and an elastic bandage. This was changed weekly. Two hundred ninety
      eight children with hand burns had a mean age of 16.8 +/- 2 months. Two hundred
      forty-eight children had partial thickness burn injuries (83%), 50 had full
      thickness burn injuries (17%), and the mean total body surface area (TBSA) was 1
      +/- 2.4%. The mean time to heal was 10.1 +/- 1.7 days for all subjects. Sixty-six
      children with foot burns were identified with a mean age of 24 +/- 2.6 months.
      Forty-six children had partial thickness injuries (70%), 20 had full thickness
      burn injuries (30%), and the mean TBSA was 2.3 +/- 2.9%. The mean time to heal
      was 14.1 +/- 2.2 days for all subjects. Weekly dressing changes using a soft
      casting technique are effective for the outpatient management of pediatric hand
      and foot burns. This method avoids costly inpatient hospital care, reduces the
      number of painful dressing changes, and allows children to heal in their own
      environment.

PMID- 29635378
TI  - FGF2 and EGF induce epithelial-mesenchymal transition in malignant pleural
      mesothelioma cells via a MAPKinase/MMP1 signal.
AB  - Malignant pleural mesothelioma (MPM), an aggressive malignancy affecting pleural
      surfaces, occurs in three main histological subtypes. The epithelioid and
      sarcomatoid subtypes are characterized by cuboid and fibroblastoid cells,
      respectively. The biphasic subtype contains a mixture of both. The sarcomatoid
      subtype expresses markers of epithelial-mesenchymal transition (EMT) and confers
      the worst prognosis, but the signals and pathways controlling EMT in MPM are not
      well understood. We demonstrate that treatment with FGF2 or EGF induced a
      fibroblastoid morphology in several cell lines from biphasic MPM, accompanied by
      scattering, decreased cell adhesion and increased invasiveness. This depended on
      the MAP-kinase pathway but was independent of TGFbeta or PI3-kinase signaling. In
      addition to changes in known EMT markers, microarray analysis demonstrated
      differential expression of MMP1, ESM1, ETV4, PDL1 and BDKR2B in response to both
      growth factors and in epithelioid versus sarcomatoid MPM. Inhibition of MMP1
      prevented FGF2-induced scattering and invasiveness. Moreover, in MPM cells with
      sarcomatoid morphology, inhibition of FGF/MAP-kinase signaling induced a more
      epithelioid morphology and gene expression pattern. Our findings suggest a
      critical role of the MAP-kinase axis in the morphological and behavioral
      plasticity of mesothelioma.

PMID- 29635379
TI  - Apremilast monotherapy in DMARD-naive psoriatic arthritis patients: results of
      the randomized, placebo-controlled PALACE 4 trial.
AB  - Objectives: The PALACE 4 trial evaluated apremilast monotherapy in patients with
      active PsA who were DMARD-naive. Methods: Eligible patients were randomized
      (1:1:1) to placebo, apremilast 20 mg twice a day or apremilast 30 mg twice a day.
      At week 16 or 24, placebo patients were rerandomized to apremilast. Double-blind
      apremilast treatment continued to week 52, with extension up to 4 years. The
      primary endpoint was the proportion of patients achieving ?20% improvement in ACR
      response criteria (ACR20) at week 16; secondary endpoints included the mean
      change in the HAQ Disability Index (HAQ-DI) score at week 16. Results: A total of
      527 patients with mean disease duration of 3.4 years and high disease activity
      were randomized and received treatment. More apremilast patients achieved ACR20
      response at week 16 [placebo, 15.9%; 20 mg, 28.0% (P = 0.0062); 30 mg, 30.7% (P =
      0.0010)]. The mean HAQ-DI improvements were -0.17 (20 mg; P = 0.0008) and -0.21
      (30 mg; P < 0.0001) vs 0.03 (placebo). Both apremilast doses showed significant
      ACR50 responses vs placebo at week 16 and improvements in secondary efficacy
      measures (swollen/tender joint counts) and psoriasis assessments, with sustained
      improvements through week 52. Common adverse events (AEs) over 52 weeks were
      diarrhoea, nausea, headache and upper respiratory tract infection; most events
      were mild or moderate. Serious AEs and AEs leading to discontinuation were
      comparable between groups. Laboratory abnormalities were infrequent and
      transient. Conclusions: In DMARD-naive patients, apremilast monotherapy improved
      PsA signs/symptoms over 52 weeks and was generally well tolerated. Trial
      registration: ClinicalTrials.gov (http://clinicaltrials.gov), NCT01307423.

PMID- 29635380
TI  - Ultrasound guidance for central venous catheterisation. A Colombian national
      survey.
AB  - Quality problem or issue: Ultrasound (US) is a widely propagated medical
      technology. Anaesthesiologists increase procedural safety by using US techniques,
      but training and availability are essential for its usage. Although its utility
      for central venous catheterisation (CVC) is well established, only a paucity of
      evidence is available regarding its use in low- and middle-income countries. This
      study is a nationwide survey of Colombian anaesthesiologists designed to explore
      the current use of US guidance for CVC. Initial assessment and implementation:
      Web-based survey at National level. Anaesthesiologists registered in the
      Colombian Society of Anaesthesiology and Resuscitation database. Choice of
      solution: Demographic variables (age and gender), anaesthesia expertise, years of
      anaesthesiology practice, US availability, use of US during CVC, reasons for not
      using US and training experience were collected. Evaluation: Of 351 respondents
      (12.3% response rate), 45% reported using US sometimes and always for CVC (95% CI
      39%-50%) (n = 157). Most anaesthesiologists obtained training in US through
      external courses (50.4%) or from colleagues (22.8%). Of the total respondents,
      62.7% (n = 220) have US equipment available at all time and this factor was
      independently associated with the use of US for CVC (adjusted odds ratio [OR] =
      38.6, P < 0.001). Lessons learned: US guidance is not a common technique used for
      CVC by Colombian anaesthesiologists; an important barrier for its use is lack of
      equipment.

PMID- 29635381
TI  - Physical, Physiological, and Dietary Comparisons Between Marine Corps Forces
      Special Operations Command Critical Skills Operators and Enablers.
AB  - Introduction: Tactical demands of a Marine Corps Forces Special Operations
      Command (MARSOC) Critical Skills Operator (CSO) require high levels of physical
      performance. During combat deployments, teams of CSOs are supplemented with
      enablers who specialize in mission-specific tasks. MARSOC CSOs and enablers serve
      alongside each other in extreme combat environments, often enduring the same
      physical demands, but the selection process for each group is very different. The
      purpose of this observational study was to quantify the physical, physiological,
      and dietary differences of MARSOC CSOs and enablers, as this may have a direct
      impact on tactical performance and provide important information to shape future
      research. Materials and Methods: Fat free mass (FFM), fat mass (FM), fat mass
      index (FMI), fat free mass index (FFMI), anaerobic power (AP), anaerobic capacity
      (AC), aerobic capacity (VO2max), knee flexion (KF), knee extension (KE), trunk
      extension (TE), and trunk flexion (TF) isokinetic strength were collected.
      Dietary intake was collected using automated self-administered 24-hr dietary
      recalls (ASA24) for a subgroup of subjects. Results: Testing on 164 male CSOs
      (age: 27.5 +/- 3.8 yr, height: 178.7 +/- 6.5 cm, mass: 85.7 +/- 9.1 kg, and 7.6
      +/- 2.9 yr of military service) and 51 male enablers (age: 27.8 +/- 5.4 yr,
      height: 178.4 +/- 8.5 cm, mass: 83.8 +/- 11.8 kg, and 7.9 +/- 5.4 yr of military
      service) showed there were no significant differences for age, height, mass, or
      years of military service. (p > 0.05). CSOs demonstrated greater physiological
      performance in AP (W/kg) (p = 0.020), AC (W/kg) (p = 0.001), and VO2max
      (ml/kg/min) (p = 0.018). There were no significant differences in FM and FFM (p >
      0.05), however CSOs demonstrated significantly higher FFMI (p = 0.011). CSOs also
      demonstrated greater KF (%BW) (p = 0.001), KE (%BW) (p = 0.001), TE (%BW) (p =
      0.010), and TF (%BW) (p = 0.016). No differences in energy or macronutrient
      intake were observed in the subgroup. Conclusions: MARSOC CSOs demonstrated
      significantly greater FFMI, AP, AC, VO2max, KF, KE, TE, and TF compared with
      enablers. Dietary intake was consistent between groups, but fueling concerns were
      identified for all personnel in the subgroup. These findings suggest the need for
      future studies to examine what physiological and strength thresholds are
      necessary to operate effectively as a member of a MSOT and determine the
      relationship between specific performance deficits and risk of injury. In
      addition, the integration of nutrition strategies that augment and optimize the
      performance of both CSOs and enablers may be beneficial.

PMID- 29635382
TI  - Exploring Mosquito Fauna of Majuro Atoll (Republic of Marshall Islands) in the
      Context of Zika Outbreak.
AB  - First autochthonous Zika clinical case was reported in the Republic of Marshall
      Islands (RMI) on Majuro Atoll in February 2016. An entomological survey of
      mosquito larvae and adult populations was carried out in four areas of Majuro,
      the most populated atoll of RMI encompassing different habitats (forest, rural,
      or urban) including some with confirmed clinical Zika cases to evaluate which
      mosquito species could be involved in the Zika transmission. A total of 2,367
      immature and adult mosquito specimens were collected and identified to the
      species level. In total, five mosquito species were detected, Aedes aegypti
      (Linnaeus), Aedes albopictus (Skuse), Aedes marshallensis (Stone and Bohart),
      Culex quinquefasciatus (Say), and Culex annulirostris (Skuse) (Diptera:
      Culicidae), a first record for RMI. The most abundant species was Ae. aegypti
      presumed to be the main vector of Zika virus followed by Ae. albopictus. Improved
      management of breeding containers through better public awareness and community
      engagement, mosquito surveillance and innovative mosquito control strategies
      using the sterile insect technique (SIT) and/or the incompatible insect technique
      (IIT) could help prevent outbreaks of arboviruses in the RMI.

PMID- 29635383
TI  - Attention Measures of Accuracy, Variability, and Fatigue Detect Early Response to
      Donepezil in Alzheimer's Disease: A Randomized, Double-blind, Placebo-Controlled
      Pilot Trial.
AB  - Objective: Donepezil is widely used to treat Alzheimer's disease (AD), but
      detecting early response remains challenging for clinicians. Acetylcholine is
      known to directly modulate attention, particularly under high cognitive
      conditions, but no studies to date test whether measures of attention under high
      load can detect early effects of donepezil. We hypothesized that load-dependent
      attention tasks are sensitive to short-term treatment effects of donepezil, while
      global and other domain-specific cognitive measures are not. Method: This
      longitudinal, randomized, double-blind, placebo-controlled pilot trial
      (ClinicalTrials.gov Identifier: NCT03073876) evaluated 23 participants newly
      diagnosed with AD initiating de novo donepezil treatment (5 mg). After baseline
      assessment, participants were randomized into Drug (n = 12) or Placebo (n = 11)
      groups, and retested after approximately 6 weeks. Cognitive assessment included:
      (a) attention tasks (Foreperiod Effect, Attentional Blink, and Covert Orienting
      tasks) measuring processing speed, top-down accuracy, orienting, intra-individual
      variability, and fatigue; (b) global measures (Alzheimer's Disease Assessment
      Scale-Cognitive Subscale, Mini-Mental Status Examination, Dementia Rating Scale);
      and (c) domain-specific measures (memory, language, visuospatial, and executive
      function). Results: The Drug but not the Placebo group showed benefits of
      treatment at high-load measures by preserving top-down accuracy, improving intra
      individual variability, and averting fatigue. In contrast, other global or
      cognitive domain-specific measures could not detect treatment effects over the
      same treatment interval. Conclusions: The pilot-study suggests that attention
      measures targeting accuracy, variability, and fatigue under high-load conditions
      could be sensitive to short-term cholinergic treatment. Given the central role of
      acetylcholine in attentional function, load-dependent attentional measures may be
      valuable cognitive markers of early treatment response.

PMID- 29635384
TI  - Pulmonary Non-Small Cell Carcinoma With Morphologic Features of Adenocarcinoma or
      "Non-Small Cell Carcinoma Favor Adenocarcinoma" in Cytologic Specimens Share
      Similar Clinical and Molecular Genetic Characteristics.
AB  - Objectives: Define if the presence of morphologic features of adenocarcinoma
      (ACA) in non-small cell lung carcinoma (NSCLC) on cytology specimens correlates
      with clinical and biologic features. Methods: A total of 209 cases of NSCLC
      diagnosed on fine-needle aspiration in a 3-year period were included. Results:
      After morphologic review, the cases were classified as ACA (n = 115), NSCLC favor
      ACA (n = 43), and NSCLC-not otherwise specified (NOS) (n = 18). Squamous cell
      (SCC) (n = 14) and NSCLC favor SCC (n = 19) were excluded from further analysis.
      Patients with EGFR-mutated tumors had longer overall survival than those with
      EGFR wild-type tumors (P = .01). When comparing cases with morphologic features
      of ACA, NSCLC favor ACA, and NSCLC-NOS, there were no differences in the presence
      or absence of tested mutations, clinical stage, or survival. Conclusion: Patients
      diagnosed with pulmonary ACA, NSCLC favor ACA, or NSCLC-NOS in cytology specimens
      have similar clinical stage, survival, and molecular alterations.

PMID- 29635385
TI  - The Fukushima Daiichi Nuclear Power Plant accident and school bullying of
      affected children and adolescents: the need for continuous radiation education.
AB  - The health threats of radiation-release incidents are diverse and long term. In
      addition to direct radiation effects, it is imperative to manage the indirect
      effects of radiation such as stigma, prejudice and broader mental health impacts.
      Six years after the Fukushima Daiichi Nuclear Power Plant accident of March 2011,
      bullying caused by stigma and prejudice toward evacuees, including children, has
      become a social problem in Japan. This phenomenon may be associated with the fact
      that knowledge about radiation has still not reached the general public, and to a
      potential lack of motivation among Japanese citizens to learn about radiation and
      bullying. Continuous and sustained education regarding radiation is warranted in
      order to enhance the general knowledge level about the effects of radiation in
      Japan after the Fukushima Daiichi Nuclear Power Plant accident, and this
      education will become an important reference for education after future nuclear
      disasters.

PMID- 29635386
TI  - Amniotic Fluid Exosome Proteomic Profile Exhibits Unique Pathways of Term and
      Preterm Labor.
AB  - Our objective was to determine the amniotic fluid-derived exosomal proteomic
      profile in patients who had spontaneous preterm birth (PTB) or preterm premature
      rupture of membranes (pPROM) compared with those who delivered at term. A cross
      sectional study of a retrospective cohort was used to quantify and determine the
      protein content of exosomes present in amniotic fluid, in PTB or pPROM, and
      normal term labor (TL) or term not in labor (TNIL) pregnancies. Exosomes were
      isolated by differential centrifugation and quantified using nanocrystals (Qdot)
      coupled to CD63 and placental alkaline phosphatase (PLAP) by fluorescence
      nanoparticle tracking analysis. The exosomal proteomic profile was identified by
      liquid chromatography-tandem mass spectrometry, and a small ion library was
      constructed to quantify the proteomic data by Sequential Window Acquisition of
      All Theoretical analysis. Ingenuity Pathway Analysis determined canonical
      pathways and biofunctions associated with dysregulated proteins. Amniotic fluid
      exosomes have similar shape and quantity regardless of the conditions; however,
      the PLAP/CD63 ratios for TL, PTB, and pPROM were significantly higher (~3.8-,
      ~4.4-, and ~3.5-fold, respectively) compared with TNIL. The PLAP/CD63 ratio was
      also significantly higher (~1.3-fold) in PTB compared with pPROM. Biological
      functions primarily indicated nonspecific inflammatory response regardless of
      condition, but unique profiles were also identified in cases (PTB and pPROM)
      compared with term. Amniotic fluid exosomes provide information specific to
      normal and abnormal parturition. Inflammatory marker enrichment and its
      uniqueness in term and preterm pregnancies support the value of exosomes in
      determining underlying physiology associated with term and preterm parturition.

PMID- 29635387
TI  - Degradation Capacity and Diapause Effects on Oviposition of Hermetia illucens
      (Diptera: Stratiomyidae).
AB  - Although well known for its organic waste decomposing capability, much of the
      biology of Hermetia illucens (L.) (Diptera: Stratiomyidae) remains unknown,
      including details involving its diapause. The present study provides a better
      understanding of the effects of diapause on the fecundity and longevity of H.
      illucens. The daily degradation rates (dry weight of the uneaten residue) of a H.
      illucens cohort were also evaluated. Data were collected and analyzed based on
      the age-stage, two-sex life table. The intrinsic rate of increase (r), finite
      rate of increase (lambda), net reproduction rate (R0), and mean generation time
      (T) were 0.0498 (d-1), 1.0511 (d-1), 118.3 offspring, and 95.8 d, respectively.
      The maximum net maternity was 22.5 eggs after 88 d. Only 12 females out of 22
      were able to successfully oviposit. The number of eggs produced per female ranged
      from 508 to 1,047. Degradation and consumption occurred during each of the 23 d
      until all larvae developed into the prepupal stage. The age-stage net consumption
      rate (Bxj) dropped at day 11 (1.05 mg) and then reached its highest level at day
      14 (1.72 mg). The mean degradation rate was 26.69 mg and the total degradation
      and consumption was 1,921.52 mg. Linking life table data and degradation rates
      provides the necessary data for predicting a population's growth and its
      degradation capacity. Results of this study demonstrated the importance of adding
      moisture during the prepupal stage. This information will provide a better
      understanding for an implementation program using H. illucens as a biodegrading
      agent of organic waste matter.

PMID- 29635388
TI  - Identification and Characterization of Compounds that Affect Stomatal Movements.
AB  - Regulation of stomatal aperture is essential for plant growth and survival in
      response to environmental stimuli. Opening of stomata induces uptake of CO2 for
      photosynthesis and transpiration, which enhances uptake of nutrients from roots.
      Light is the most important stimulus for stomatal opening. Under drought stress,
      the plant hormone ABA induces stomatal closure to prevent water loss. However,
      the molecular mechanisms of stomatal movements are not fully understood. In this
      study, we screened chemical libraries to identify compounds that affect stomatal
      movements in Commelina benghalensis and characterize the underlying molecular
      mechanisms. We identified nine stomatal closing compounds (SCL1-SCL9) that
      suppress light-induced stomatal opening by >50%, and two compounds (temsirolimus
      and CP-100356) that induce stomatal opening in the dark. Further investigations
      revealed that SCL1 and SCL2 had no effect on autophosphorylation of phototropin
      or the activity of the inward-rectifying plasma membrane (PM) K+ channel, KAT1,
      but suppressed blue light-induced phosphorylation of the penultimate residue,
      threonine, in PM H+-ATPase, which is a key enzyme for stomatal opening. SCL1 and
      SCL2 had no effect on ABA-dependent responses, including seed germination and
      expression of ABA-induced genes. These results suggest that SCL1 and SCL2
      suppress light-induced stomatal opening at least in part by inhibiting blue light
      induced activation of PM H+-ATPase, but not by the ABA signaling pathway.
      Interestingly, spraying leaves onto dicot and monocot plants with SCL1 suppressed
      wilting of leaves, indicating that inhibition of stomatal opening by these
      compounds confers tolerance to drought stress in plants.

PMID- 29635389
TI  - Hrp48 and eIF3d contribute to msl-2 mRNA translational repression.
AB  - Translational repression of msl-2 mRNA in females of Drosophila melanogaster is
      an essential step in the regulation of X-chromosome dosage compensation.
      Repression is orchestrated by Sex-lethal (SXL), which binds to both untranslated
      regions (UTRs) of msl-2 and inhibits translation initiation by poorly understood
      mechanisms. Here we identify Hrp48 as a SXL co-factor. Hrp48 binds to the 3' UTR
      of msl-2 and is required for optimal repression by SXL. Hrp48 interacts with
      eIF3d, a subunit of the eIF3 translation initiation complex. Reporter and RNA
      chromatography assays showed that eIF3d binds to msl-2 5' UTR, and is required
      for efficient translation and translational repression of msl-2 mRNA. In line
      with these results, eIF3d depletion -but not depletion of other eIF3 subunits- de
      represses msl-2 expression in female flies. These data are consistent with a
      model where Hrp48 inhibits msl-2 translation by targeting eIF3d. Our results
      uncover an important step in the mechanism of msl-2 translation regulation, and
      illustrate how general translation initiation factors can be co-opted by RNA
      binding proteins to achieve mRNA-specific control.

PMID- 29635391
TI  - A005, a novel inhibitor of phosphatidylinositol 3-kinase/mammalian target of
      rapamycin, prevents osteosarcoma-induced osteolysis.
AB  - Osteosarcoma is the most frequent primary bone tumor in children and adolescents.
      The phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR)
      signaling pathway is an attractive anticancer target because it plays key roles
      in the regulation of cell growth, division and differentiation. In this study, we
      demonstrated high expression of PI3K/mTOR signaling pathway-related genes in
      patients with osteosarcoma. We thus investigated the effects of A005, a newly
      synthesized dual PI3K/mTOR inhibitor, on osteosarcoma cells and in a mouse
      xenograft tumor model. The results confirmed that A005 inhibited the
      proliferation, migration and invasion of human osteosarcoma cells. In addition,
      A005 also inhibited receptor activator of nuclear factor kappa-B ligand (RANKL)
      induced osteoclast differentiation and bone resorption in vitro. Therefore, A005
      was further applied to a SaOS-2 osteosarcoma-induced mouse osteolysis model. A005
      inhibited tumor growth and prevented osteosarcoma-associated osteolysis via
      modulation of the PI3K/AKT/mTOR pathway. Overall, our results showed that A005
      inhibited osteoclastogenesis and prevented osteosarcoma-induced bone osteolysis
      by suppressing PI3K/AKT/mTOR signaling. These findings indicated that A005 may be
      a promising candidate drug for the treatment of human osteosarcoma.

PMID- 29635390
TI  - RAD51 foci as a functional biomarker of homologous recombination repair and PARP
      inhibitor resistance in germline BRCA-mutated breast cancer.
AB  - Background: BRCA1 and BRCA2 (BRCA1/2)-deficient tumors display impaired
      homologous recombination repair (HRR) and enhanced sensitivity to DNA damaging
      agents or to poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi). Their
      efficacy in germline BRCA1/2 (gBRCA1/2)-mutated metastatic breast cancers has
      been recently confirmed in clinical trials. Numerous mechanisms of PARPi
      resistance have been described, whose clinical relevance in gBRCA-mutated breast
      cancer is unknown. This highlights the need to identify functional biomarkers to
      better predict PARPi sensitivity. Patients and methods: We investigated the in
      vivo mechanisms of PARPi resistance in gBRCA1 patient-derived tumor xenografts
      (PDXs) exhibiting differential response to PARPi. Analysis included exome
      sequencing and immunostaining of DNA damage response proteins to functionally
      evaluate HRR. Findings were validated in a retrospective sample set from gBRCA1/2
      cancer patients treated with PARPi. Results: RAD51 nuclear foci, a surrogate
      marker of HRR functionality, were the only common feature in PDX and patient
      samples with primary or acquired PARPi resistance. Consistently, low RAD51 was
      associated with objective response to PARPi. Evaluation of the RAD51 biomarker in
      untreated tumors was feasible due to endogenous DNA damage. In PARPi-resistant
      gBRCA1 PDXs, genetic analysis found no in-frame secondary mutations, but BRCA1
      hypomorphic proteins in 60% of the models, TP53BP1-loss in 20% and RAD51
      amplification in one sample, none mutually exclusive. Conversely, one of three
      PARPi-resistant gBRCA2 tumors displayed BRCA2 restoration by exome sequencing. In
      PDXs, PARPi resistance could be reverted upon combination of a PARPi with an
      ataxia-telangiectasia mutated (ATM) inhibitor. Conclusion: Detection of RAD51
      foci in gBRCA tumors correlates with PARPi resistance regardless of the
      underlying mechanism restoring HRR function. This is a promising biomarker to be
      used in the clinic to better select patients for PARPi therapy. Our study also
      supports the clinical development of PARPi combinations such as those with ATM
      inhibitors.

PMID- 29635392
TI  - Do plasma neprilysin activity and plasma neprilysin concentration predict cardiac
      events in chronic kidney disease patients?
AB  - Background: Since the introduction of sacubitril/valsartan in clinical
      cardiology, neprilysin has become a major target for heart failure treatment.
      Plasma neprilysin concentration has been discussed as a novel biomarker that
      predicts cardiac events. Natriuretic peptides may inhibit plasma neprilysin. As
      they accumulate in chronic kidney disease (CKD), we hypothesized that high plasma
      neprilysin loses its predictive role in CKD patients. Methods: We measured plasma
      levels of neprilysin concentration, neprilysin activity and brain natriuretic
      peptide (BNP) in 542 CKD G2-G4 patients within the CARE FOR HOMe study. Patients
      were followed for predefined endpoints of hospitalization for acute decompensated
      heart failure and incident atherosclerotic cardiovascular events. Results: During
      5.1 +/- 2.1 years, 63 patients had acute decompensated heart failure and 125
      patients had incident atherosclerotic cardiovascular events. In both Kaplan-Meier
      and multivariate Cox regression analyses, high plasma BNP and low, rather than
      elevated, neprilysin activity predicted future hospitalization for acute
      decompensated heart failure; neprilysin concentration was not predictive.
      Furthermore, only BNP was an independent predictor of incident atherosclerotic
      cardiovascular events. Conclusions: In line with experimental studies, high
      natriuretic peptides may inhibit neprilysin activity in CKD. Therefore, high
      neprilysin activity and concentrations are not predictors of adverse
      cardiovascular outcome in CKD patients. Thus neprilysin inhibitors should be
      implemented with caution in patients with advanced CKD.

PMID- 29635393
TI  - Calvarial Volume Loss and Facial Aging: A Computed Tomographic (CT)-Based Study.
AB  - Background: Our understanding of the aging changes involving the cranium and its
      impact on the overlying soft tissues is limited. Objectives: This study was
      designed to look at the changes that occur in the cranium with aging and to
      propose an additional mechanism for loss of support for overlying soft tissues.
      Methods: One hundred and fifty-seven white individuals (10 males and 10 females
      in each decade: 20-29 years, 30-39 years, 40-49 years, 50-59 years, 60-69 years,
      70-79 years, 80-89 years, and 8 males and 9 females aged 90-98 years) were
      investigated. Computed tomographic (CT) multiplanar scans with standardized
      measurements of cranial thickness were performed for the frontal bone, nasion,
      vertex, pterion, lambda, calvarial and midfacial height, and sagittal and
      transverse diameter. Results: Increasing age correlated with a decrease in
      sagittal diameter in both males (rp = -0.201) and females (rp = -0.055) but with
      an increase in transverse diameter in both males (rp = 0.233) and females (rp =
      0.207). Frontal bone thickness decreased in males -1.57mm/-18.14%, whereas it
      increased slightly in females +0.26mm/+3.04%. At the pterion, bone thickness
      increased significantly in both genders. Calvarial volume decreased with
      increased age in both males and females: -70.2 ml/-5.35% and -61.4 ml/-5.10%,
      respectively. Conclusions: The lateral expansion of the skull may favor a
      skeletonized appearance of the face in elderly individuals. The computed volume
      of the calvaria decreased with advancing age in both genders, providing an
      additional element in the multifactorial model for facial soft-tissue laxity.
      Level of Evidence 2: 

PMID- 29635394
TI  - Field of genes: using Apache Kafka as a bioinformatic data repository.
AB  - Background: Bioinformatic research is increasingly dependent on large-scale
      datasets, accessed either from private or public repositories. An example of a
      public repository is National Center for Biotechnology Information's (NCBI's)
      Reference Sequence (RefSeq). These repositories must decide in what form to make
      their data available. Unstructured data can be put to almost any use but are
      limited in how access to them can be scaled. Highly structured data offer
      improved performance for specific algorithms but limit the wider usefulness of
      the data. We present an alternative: lightly structured data stored in Apache
      Kafka in a way that is amenable to parallel access and streamed processing,
      including subsequent transformations into more highly structured representations.
      We contend that this approach could provide a flexible and powerful nexus of
      bioinformatic data, bridging the gap between low structure on one hand, and high
      performance and scale on the other. To demonstrate this, we present a proof-of
      concept version of NCBI's RefSeq database using this technology. We measure the
      performance and scalability characteristics of this alternative with respect to
      flat files. Results: The proof of concept scales almost linearly as more compute
      nodes are added, outperforming the standard approach using files. Conclusions:
      Apache Kafka merits consideration as a fast and more scalable but general-purpose
      way to store and retrieve bioinformatic data, for public, centralized reference
      datasets such as RefSeq and for private clinical and experimental data.

PMID- 29635395
TI  - Clinical, Empirical, and Theoretical Rationale for Selection of Accelerated
      Resolution Therapy for Treatment of Post-traumatic Stress Disorder in VA and DoD
      Facilities.
AB  - Introduction: Post-traumatic stress disorder (PTSD) is a chronic, disabling
      psychiatric disorder prevalent among U.S. service members and veterans. First
      line treatments for PTSD endorsed in the 2017 Veterans Affairs (VA)/Department of
      Defense (DoD) Clinical Practice Guideline for PTSD emphasize individual,
      manualized trauma-focused psychotherapies that have a primary component of
      exposure and/or cognitive restructuring. These include prolonged exposure (PE)
      therapy, cognitive processing therapy (CPT), eye movement desensitization and
      reprocessing (EMDR), and others. Accelerated resolution therapy (ART) is an
      emerging trauma-focused therapy not specifically referenced in the guideline, but
      one that is consistent with the recommendations and is derived directly from
      EMDR. One randomized clinical trial and multiple observational studies have
      suggested that ART can be delivered in an average of just four treatment
      sessions. This commentary reviews the clinical, empirical, and theoretical
      rationale for use of ART as a potential first-line PTSD treatment modality in VA
      and DoD facilities. Materials and Methods: The clinical protocol of ART is
      summarized into discrete procedural steps. The theoretical rationale as to how
      ART may help clients process traumatic memories and resolve symptoms of PTSD is
      also discussed, including how repeated sets of smooth pursuit horizontal eye
      movements may facilitate a relaxation response and assist with processing
      emotionally intrusive memories. Herein, we review primary treatment results from
      four published studies of ART, including mean symptom score reductions on the 17
      item PCL (PTSD checklist) after treatment with ART, along with effect sizes and
      percentage of treatment responders. Finally, the ART protocol is compared
      directly against specific recommended elements of trauma-focused therapy
      described in the VA/DoD Clinical Practice Guideline. Results: The four published
      studies of ART reviewed (n = 291) included adult civilians and service
      members/veterans; the mean age was 42.3 +/- 12.3 yr and 28.9% were female. Among
      237 treatment completers (81.4% of the combined cohort), the mean number of ART
      sessions received was 3.9 +/- 1.1. Across the four studies, mean treatment
      related reductions in PCL scores ranged from 15.6 +/- 13.2 to 25.6 +/- 11.3, with
      a pooled mean reduction on the PCL of 20.6 +/- 15.0. Effect sizes were large and
      ranged from 1.18 to 2.26 (p< 0.0005) across studies, with a pooled effect size of
      1.38 (95% confidence interval: 1.20-1.56, p < 0.0001). Using the clinical
      cutpoint of >10-point reduction on the PCL instrument, clinically significant
      change (response) ranged from 63.8% to 100.0% across the four studies, with a
      pooled treatment response rate of 74.7%. Results were nominally attenuated when
      conservatively assuming no treatment response for non-completers. Conclusion: The
      ART protocol contains the core therapeutic elements and aligns closely with the
      current VA/DoD Clinical Practice Guideline. It has a plausible theoretical
      rationale and an evolving empirical research base that includes four studies with
      peer-reviewed publications, one of which was a randomized controlled trial. These
      features, along with the brevity of the treatment protocol, no requirement for
      narration, and high provider satisfaction rates, provide a rationale for the
      potential use of ART as a first-line PTSD treatment modality for active duty and
      veteran military personnel.

PMID- 29635396
TI  - Takayasu arteritis: advanced understanding is leading to new horizons.
AB  - Although outcomes in Takayasu arteritis (TAK) are improving, diagnosis is
      typically delayed and significant arterial injury accrues. While wider use of non
      invasive imaging is impacting this, the onus remains with clinicians to consider
      a diagnosis of TAK earlier. Meanwhile, morbidity and mortality in TAK remains
      increased. Herein we review the current situation, outline recent advances and
      summarize remaining challenges. Understanding of disease pathogenesis remains
      poor. However, recent genetic data and identification of pathogenic cytokines may
      facilitate the search for biomarkers capable of distinguishing active and
      inactive disease, inflammatory and non-inflammatory arterial remodelling. Imaging
      is critical for TAK, and each modality has important strengths and limitations.
      Dependence upon CS therapy remains too high. However, the impact of combination
      immunosuppressive therapy is now recognized, biologic therapies are increasingly
      available and new agents offer promise. Multicentre clinical trials are now
      required, and these will depend upon development of defined clinical and imaging
      end-points.

PMID- 29635397
TI  - Simultaneous Determination of Antipsychotic Drugs and Their Active Metabolites by
      LC-MS-MS and its Application to Therapeutic Drug Monitoring.
AB  - A quantitative method was developed to support therapeutic drug monitoring of
      eight antipsychotic drugs: chlorpromazine, haloperidol, zuclopenthixol,
      clozapine, risperidone, quetiapine, aripiprazole or olanzapine and some active
      metabolites (dehydroaripiprazole, N-desmethylclozapine and 9-hydroxyrisperidone)
      in human serum. Separation of the compounds was achieved using a Zorbax SB-C18
      (150 mm * 4.6 mm, 5 MUm) column and mass-spectrometric detection in multiple
      reaction monitoring mode. Human blood samples were collected in vacutainer tubes
      and the analytes were extracted with methyl-tert-butyl ether. The lower limits of
      quantitation were equal 0.5-1 ng/mL for all analytes. The method was applied with
      success to serum samples from schizophrenic patients undergoing polypharmacy with
      two or more different antipsychotic drugs. Precision data, accuracy results were
      satisfactory, and no interference from other psychotropic drugs was found. Hence,
      the method is suitable for the TDM of the analytes in psychotic patients' serum.

PMID- 29635398
TI  - The predictive value of new-onset atrial fibrillation on postoperative morbidity
      after esophagectomy.
AB  - New-onset atrial fibrillation (AF) is frequently observed following esophagectomy
      and may predict other complications. The aim of the current study was to
      determine the association between, and the possible predictive value of, new
      onset AF and infectious complications following esophagectomy. Consecutive
      patients who underwent elective esophagectomy with curative intent for esophageal
      cancer between 2004 and 2016 in the University Medical Center Utrecht were
      included from a prospective database. The date of diagnosis of the complications
      included in the current analysis was retrospectively collected from the
      computerized medical record. The association between new-onset AF and infectious
      complications was studied in univariable and multivariable logistic regression
      analyses. A total of 455 patients were included. In 93 (20.4%) patients new-onset
      AF was encountered after esophagectomy. There were no significant differences in
      patient and treatment-related characteristics between the patients with and
      without AF. In 9 (9.7%) patients, AF was the only adverse event following
      surgery. In multivariable analyses, AF was significantly associated with
      infectious complications in general (OR 3.00, 95% CI: 1.73-5.21). More
      specifically, AF was associated with pulmonary complications (OR 2.06, 95% CI:
      1.29-3.30), pneumonia (OR 2.41, 95% CI: 1.48-3.91) and anastomotic leakage (OR
      3.00, 95% CI: 1.80-4.99). In patients who underwent esophagectomy, new-onset AF
      was highly associated with infectious complications. AF may serve as an early
      clinical warning sign for anastomotic leakage. Therefore, further evaluation of
      patients who develop new-onset AF after esophagectomy is warranted.

PMID- 29635399
TI  - Does the Visual Channel Improve the Perception of Consonants Produced by Speakers
      of French With Down Syndrome?
AB  - Purpose: This work evaluates whether seeing the speaker's face could improve the
      speech intelligibility of adults with Down syndrome (DS). This is not
      straightforward because DS induces a number of anatomical and motor anomalies
      affecting the orofacial zone. Method: A speech-in-noise perception test was used
      to evaluate the intelligibility of 16 consonants (Cs) produced in a vowel
      consonant-vowel context (Vo = /a/) by 4 speakers with DS and 4 control speakers.
      Forty-eight naive participants were asked to identify the stimuli in 3
      modalities: auditory (A), visual (V), and auditory-visual (AV). The probability
      of correct responses was analyzed, as well as AV gain, confusions, and
      transmitted information as a function of modality and phonetic features. Results:
      The probability of correct response follows the trend AV > A > V, with smaller
      values for the DS than the control speakers in A and AV but not in V. This trend
      depended on the C: the V information particularly improved the transmission of
      place of articulation and to a lesser extent of manner, whereas voicing remained
      specifically altered in DS. Conclusions: The results suggest that the V
      information is intact in the speech of people with DS and improves the perception
      of some phonetic features in Cs in a similar way as for control speakers. This
      result has implications for further studies, rehabilitation protocols, and
      specific training of caregivers. Supplemental Material:
      https://doi.org/10.23641/asha.6002267.

PMID- 29635400
TI  - Time needed to resolve patient complaints and factors influencing it: a cohort
      study.
AB  - Objective: There has been an increase in the number and complexity of patient
      complaints against healthcare institutions. An understanding of the resources
      needed in this area is important for proper planning. Design: Cohort study.
      Setting: A 1250-bed tertiary-care teaching hospital. Participants: All patient
      complaints received between 1 February 2014 and 31 January 2015 were
      prospectively included in this cohort study. Main Outcome Measures: The amount of
      time spent on the investigation and liaising with the complainant for each case
      was recorded. The complainant's personal details and characteristics were
      recorded anonymously. Results: In total, 908 patient complaints were recorded
      from 801 individuals during the study period. Longer median person-hours were
      spent on managing complaints that were brought forward by men (1.48 h), those who
      were distant relatives of the patients (2.08 h), foreigners (1.58 h) and non
      subsidised patients (1.83 h). Patient complaints falling into the categories of
      clinical domain (3.00 h) and patient rights (2.54 h), quality (3.00 h) and safety
      (2.83 h) required the longest median time to manage. Multiple logistic regression
      analysis revealed that the total amount of time spent on the complaints was
      predicted by the gender of the complainant, the relationship of the complainant
      with the patient, the subsidy status of the patient, the severity and the domain
      of the complaint. Conclusions: This study reported the time required to manage
      patient complaints in a larger tertiary-care academic medical centre. Predictors
      of the time spent on resolving patient complaints can be used as parameters for
      resource planning.

PMID- 29635401
TI  - One hundred and fifty-six cases of anatomical pulmonary segmentectomy by
      uniportal video-assisted thoracic surgery: a 2-year learning experience.
AB  - OBJECTIVES: Our goal was to explore the outcome of the study and the feasibility
      for patients of the technique of anatomical pulmonary segmentectomy by uniportal
      video-assisted thoracic surgery (VATS). METHODS: A total of 156 consecutive
      patients with lung lesions who received anatomical pulmonary segmentectomy by
      VATS between 2015 and 2016 in our hospital were enrolled. All the subjects had
      high-resolution, thin-section chest computed tomography (CT) examinations with 3
      dimensional reconstruction, a pulmonary function test, abdominal ultrasonography,
      electrocardiogram and cardiac ultrasonography. The lung lesion was localized
      before the operation using CT reconstruction or a hookwire to plan the operative
      method. RESULTS: Uniportal VATS pulmonary segmentectomy was successfully
      completed in 151 (96.8%) patients. Most cases involved the right apical and
      apical posterior segments and the left trisegment. Only 1 patient had a right
      middle interior segmentectomy, left upper apical anterior segmentectomy or a
      right lower posteriolateral segmentectomy, respectively. There were 26 cases of
      benign lesions (including 17 cases of atypical hyperplasia) and 130 cases of non
      small-cell lung cancer. Operation time (146 +/- 56 vs 113 +/- 32 min), blood loss
      (63 +/- 17 vs 54 +/- 13 ml) and complication rates (13.5% vs 5.8%) were obviously
      lower in 2016 compared with 2015 (P < 0.01). In contrast, the preoperative
      hookwire localization rate was markedly higher in 2016 compared with 2015.
      CONCLUSIONS: Uniportal VATS anatomical pulmonary segmentectomy is safe and
      feasible in clinical applications. Compared with the 2- or 3-port method, there
      were some technical difficulties in the early phase of the learning curve for
      uniportal VATS that were overcome through a period of practice.

PMID- 29635402
TI  - Effect of intensive diet and exercise on self-efficacy in overweight and obese
      adults with knee osteoarthritis: The IDEA randomized clinical trial.
AB  - Physical activity decreases the risk of osteoarthritis (OA)-related disability;
      however, pain and lack of confidence represent barriers for older adults with
      knee OA. The purpose of this study was to examine (a) the baseline associations
      among self-efficacy and physical activity, function, and pain; (b) longitudinal
      changes in self-efficacy; and (c) whether self-efficacy mediates treatment
      effects on clinical outcomes. The Intensive Diet and Exercise for Arthritis
      (IDEA) trial was a single-blind, randomized controlled 18-month study including
      454 overweight/obese older adults (M age = 66 years) with knee OA. Participants
      were randomized to one of three interventions: exercise (E), diet-induced weight
      loss (D), or both (D+E). Self-efficacy for gait, balance, and walking duration
      were assessed at baseline, 6 months, and 18 months. Baseline associations were
      tested using Pearson correlations, and group least squares means were compared
      using mixed linear models at follow-up. Participants with higher self-efficacy
      reported significantly better physical function and less knee pain at baseline,
      walked farther (6-min walk), and were more physically active (all |r| > 0.12, all
      p < .01). Significant differences between groups were detected for all self
      efficacy measures at 18 months; the D+E group reported significantly (all p <
      .005) higher self-efficacy for gait, walking duration, and balance compared with
      the D- or E-only groups. Self-efficacy significantly (p < .05) mediated treatment
      effects on physical function and pain at 18 months. A combined intervention of
      diet-induced weight loss and exercise is the treatment of choice to maximize self
      efficacy, improve physical function, and reduce pain in overweight/obese adults
      with knee OA.

PMID- 29635403
TI  - C5-C6 Cervical Spinal Cord Cavernous Malformation Microsurgical Resection: 2
      Dimensional Operative Video.
AB  - We describe the case of a previously healthy 44-yr-old female patient presenting
      with a sudden onset of numbness, paresthesias, and decreased sensation in her
      lower limbs. Physical examination revealed a decreased sensation to vibration and
      light touch in her lower extremities, primarily in the left limb. Impaired
      proprioception was also evident primarily in the left toe. Full strength with 2+
      reflexes was observed in all extremities. Magnetic resonance imaging demonstrated
      an exophytic lesion in the posterior aspect of the cervical spinal cord at the C5
      C6 level, with a hemosiderin halo, consistent with a cavernous malformation.
      Given the evidence of past hemorrhage and the location of the lesion,
      microsurgical intervention was indicated. A midline cervical C5-C6 laminectomy
      under neurophysiologic monitoring was performed, and complete resection of the
      lesion was achieved with mild improvement of the sensitive symptoms and no
      evidence of new motor deficits. Any microsurgical resection of a cervical spinal
      cord lesion can be technically difficult and adequate patient selection with
      evaluation of the accessibility to the lesion is key.1 Surgical resection of
      cavernous malformations in selected patients eliminates the risk of future
      hemorrhage and may achieve satisfactory outcomes comparable to patients who
      undergo conservative management.2 In the following video illustration, we narrate
      this operative case, and highlight the nuances of this approach. Patient consent
      was obtained for the submission of the video to this journal.

PMID- 29635406
TI  - Corrigendum.

PMID- 29635404
TI  - Species Identity Supersedes the Dilution Effect Concerning Hantavirus Prevalence
      at Sites across Texas and Mexico.
AB  - Recent models suggest a relationship exists between community diversity and
      pathogen prevalence, the proportion of individuals in a population that are
      infected by a pathogen, with most inferences tied to assemblage structure. Two
      contrasting outcomes of this relationship have been proposed: the "dilution
      effect" and the "amplification effect." Small mammal assemblage structure in
      disturbed habitats often differs from assemblages in sylvan environments, and
      hantavirus prevalence is often negatively correlated with habitats containing
      high species diversity via dilution effect dynamics. As species richness
      increases, prevalence of infection often is decreased. However, anthropogenic
      changes to sylvan landscapes have been shown to decrease species richness and/or
      increase phylogenetic similarities within assemblages. Between January 2011 and
      January 2016, we captured and tested 2406 individual small mammals for hantavirus
      antibodies at 20 sites across Texas and Mexico and compared differences in
      hantavirus seroprevalence, species composition, and assemblage structure between
      sylvan and disturbed habitats. We found 313 small mammals positive for antibodies
      against hantaviruses, evincing an overall prevalence of 9.7% across all sites. In
      total, 40 species of small mammals were identified comprising 2 taxonomic orders
      (Rodentia and Eulipotyphla). By sampling both habitat types concurrently, we were
      able to make real-world inferences into the efficacy of dilution effect theory in
      terms of hantavirus ecology. Our hypothesis predicting greater species richness
      higher in sylvan habitats compared to disturbed areas was not supported,
      suggesting the characteristics of assemblage structure do not adhere to current
      conceptions of species richness negatively influencing prevalence via a dilution
      effect.

PMID- 29635405
TI  - The Effects of Caloric Education, Trial-by-Trial Feedback, and their Interaction
      on College-Aged Women's Abilities to Estimate Caloric Content.
AB  - Background: Many people track the caloric content of food, given its relevance to
      weight loss, gain, or maintenance. A better understanding of the psychological
      underpinnings of caloric-content estimation for unhealthy foods is of significant
      psychological and public-health interest. Purpose: This study investigated
      whether college-aged women could be trained to estimate the caloric content of
      unhealthy foods more accurately via exposure to caloric-content education, trial
      by-trial feedback, and their combination. Methods: The caloric content of 84
      foods was estimated and three transfer tasks were completed by 238 undergraduate
      women. Mixed-effects modeling estimated three aspects of the quadratic function
      linking true and judged caloric content: threshold (average perceived caloric
      content), linear sensitivity, and change in sensitivity as caloric content
      increases. Results: On average, college-aged women underestimated caloric
      content, demonstrated substantial linear sensitivity to caloric content, and did
      not show reduced sensitivity as caloric content increased. Trial-by-trial
      feedback, but not Caloric Education, enhanced caloric estimation on the first two
      tasks. Conclusions: College-aged women show biased but sensitive judgments of the
      caloric content of unhealthy food presented in images. Initial evidence suggests
      that trial-by-trial feedback may be an efficacious strategy to enhance caloric
      content estimation, at least when viewing static images of foods.

PMID- 29635407
TI  - Job Stressors and Employment Precarity as Risks for Thoughts About Suicide: An
      Australian Study Using the Ten to Men Cohort.
AB  - Aims: Past research suggests that adverse experiences at work (such as job
      stressors and precarious employment) are associated with thoughts about suicide,
      especially among males. A limitation of this research is that it is largely cross
      sectional. Thus, it is unknown whether job stressors are a prior cause of
      thoughts about suicide. This study examined the baseline association between
      adverse experiences at work and thoughts about suicide at follow-up in a large
      nationally representative cohort of employed men. Methods: We used data from the
      Australian Longitudinal Study on Male Health (Ten to Men). The outcome was
      thoughts about suicide in the prior 12 months (reported in wave 2) and the key
      exposure variables were: high job demands, low job control, job insecurity,
      perceived unfairness of pay, occupational skill level, and employment arrangement
      (all reported in wave 1). We adjusted for possible confounders, including mental
      health and suicidal thoughts (wave 1). Results: In a sample of 8379 and after
      adjustment, job insecurity (OR 1.35, 95% CI 1.13-1.61, P = 0.001), low job
      control (OR 1.19, 95% CI 1.06-1.33, P = 0.004), and employment on a casual or on
      a fixed term basis (OR 1.30, 95% 1.01-1.67, P = 0.041) were associated with a
      greater odds of thoughts about suicide at follow up. Results for all by job
      control were maintained after removing those who reported thoughts of suicide at
      baseline. Conclusion: This study suggests that experiences at work may be risk
      factors for thoughts about suicide among employed men. More research is needed to
      unpack the complex associations between, employment, and experiences of suicide.

PMID- 29635408
TI  - Acceptability and Suitability of Three Liriomyza Leafminer Species as Host for
      the Endoparasitoid Chrysocharis flacilla (Hymenoptera: Eulophidae).
AB  - Liriomyza leafminers represent important threats to the horticulture sector in
      East Africa. Parasitism rates of local parasitoids are reported to be low and the
      endoparasitoid, Chrysocharis flacilla (Walker) (Hymenoptera: Eulophidae), was
      introduced in Kenya for a classical biological control program. Acceptability and
      suitability bioassays were conducted on the three economically important
      Liriomyza species in Africa (Liriomyza huidobrensis (Blanchard) (Diptera:
      Agromyzidae), Liriomyza sativae (Blanchard) (Diptera: Agromyzidae), and Liriomyza
      trifolii (Burgess) (Diptera: Agromyzidae). Foraging behavior, developmental time,
      sex ratio, parasitism rates, host pupal mortality, and body indices of C.
      flacilla were assessed. Results showed that the three Liriomyza leafminer species
      were accepted and suitable to C. flacilla. Foraging time was significantly
      shorter on L. trifolii than on L. sativae and L. huidobrensis. Ninety-eight per
      cent of females successfully oviposited in the three-host species. Female
      parasitoids were significantly aggressive in attempting to oviposit on L.
      huidobrensis than on L. sativae and L. trifolii. High parasitism rates ranging
      between 73 and 78% were observed from the three Liriomyza hosts, but no
      significant difference among hosts. C. flacilla-induced significant
      nonreproductive pupal mortality ranging from 23 to 35%, an attribute rare among
      endoparasitoids. In all three Liriomyza hosts, the parasitoid progeny was female
      biased. Parasitoid development period ranged between 16 and 24 d. Female
      parasitoids reared on L. huidobrensis were significantly bigger than those reared
      on L. sativae and L. trifolii. The acceptance to local Liriomyza leafminers and
      high host suppression ability is potential for considerations of C. flacilla in
      the management of Liriomyza spp. in Africa.

PMID- 29635409
TI  - Whole-genome resequencing reveals signatures of selection and timing of duck
      domestication.
AB  - Background: The genetic basis of animal domestication remains poorly understood,
      and systems with substantial phenotypic differences between wild and domestic
      populations are useful for elucidating the genetic basis of adaptation to new
      environments as well as the genetic basis of rapid phenotypic change. Here, we
      sequenced the whole genome of 78 individual ducks, from two wild and seven
      domesticated populations, with an average sequencing depth of 6.42X per
      individual. Results: Our population and demographic analyses indicate a complex
      history of domestication, with early selection for separate meat and egg
      lineages. Genomic comparison of wild to domesticated populations suggests that
      genes that affect brain and neuronal development have undergone strong positive
      selection during domestication. Our FST analysis also indicates that the duck
      white plumage is the result of selection at the melanogenesis-associated
      transcription factor locus. Conclusions: Our results advance the understanding of
      animal domestication and selection for complex phenotypic traits.

PMID- 29635411
TI  - Should decisions on adding adjuvant chemotherapy in early-stage ER-positive
      breast cancer be based on gene expression testing or clinicopathologic factors or
      both?

PMID- 29635413
TI  - Correction and Prevention of the Pixie Ear Deformity: A Combined Technique.
AB  - Background: Ear and earlobe deformities after surgical rhytidectomy are common
      and can significantly diminish the aesthetic outcome. The main causes of
      ear/earlobe distortion are skin over-resection, an imbalance between
      vertical/horizontal skin-lift vectors, and tractional distortions through
      superficial muscularaponeurotic system (SMAS) tension. Objective: To demonstrate
      a new method for earlobe suturing and ear fixation that would prevent aesthetics
      related complications after facelift surgery. Methods: A total of 105 primary
      SMAS facelift surgeries were performed between 2015 and 2016 by the first author.
      A combination technique consisting of a posterior earlobe rotation flap (PERF)
      and a concha-mastoid suspension suture (CMSS) was executed bilaterally within
      each facelift procedure (n=210). A retrospective data analysis was conducted
      (preoperatively and one year postoperatively) using our hospital information
      system and a photometric data analysis to assess auricular displacement, earlobe
      distortion, and hypertrophic scarring. Results: Pseudoptosis of the earlobe was
      noted in two cases, and auricular displacement was observed in four cases.
      Bilateral mild hypertrophic scarring was seen in one patient. The postoperative
      photometric analysis showed a natural ptosis grade I/II in all the patients, with
      a statistically significantly reduced postoperative earlobe size (p<0.05). The
      total rate of aesthetics-related complications was 4% in our cohort (earlobe
      distortion with pseudoptosis: 1%; auricular displacement: 2%; hypertrophic
      scarring: 1%). Conclusions: Our modification of the facial flap anchoring at the
      ear base in combination with a CMSS stabilizes the natural position of the ear
      and prevents distortion while allowing better control over the earlobe's
      aesthetic shaping. This novel method reduces the incidence of ear/earlobe
      deformities and hypertrophic scarring at the ear base after rhytidectomy and,
      therefore, promises to be a valuable advancement.

PMID- 29635412
TI  - Nutritive value of corn distiller's dried grains with solubles steeped without or
      with exogenous feed enzymes for 24 h and fed to growing pigs.
AB  - The use of corn distillers dried grains with solubles (DDGS) in pig diets is
      limited due to high fiber concentration. Steeping with exogenous fiber-degrading
      enzymes (FDE) may improve their feeding value. We evaluated apparent ileal
      digestibility (AID), standardized ileal digestibility (SID), and apparent total
      tract digestibility (ATTD) of components and DE content in DDGS steeped without
      or with two commercial FDE (A and B). Mixture of 350 g of DDGS, FDE (none for
      control), and 1.5 liters of water was incubated at 40  degrees C for 24 h with 15
      min agitation every 40 min. FDE-A (pure combination) supplied 5,500 U of xylanase
      and 1,050 U of beta-glucanase while FDE-B (multienzyme complex) supplied 1,200 U
      of xylanase, 150 U of beta-glucanase, 500 U of cellulase, and 5,000 U of protease
      per kg of DDGS plus side activities. Samples were taken at time 0, 4, 8, and 24 h
      for organic acids and pH measurements. Three semi-purified corn starch-based
      diets were formulated with steeped DDGS as the sole source of CP. The basal
      mixture contained 0.2% TiO2 as indigestible marker. Six ileal-cannulated pigs (20
      kg BW) were fed the three diets in a replicated 3 * 3 Latin square design to give
      six replicates per diet. Pigs were fed at 2.8* maintenance energy requirements
      and had free access to water. In each period, pigs were adjusted to diets for 7 d
      followed by 2 d for grab fecal and 2 d of 8 h continuous ileal digesta
      collection. There were no (P > 0.05) treatment and sampling time interaction or
      treatment effects on pH and lactic concentration. Lactic and acetic acids
      increased, and pH decreased (P < 0.05) over time points. The AID of CP, NDF, and
      crude fat and SID of CP were not different (P > 0.05) among treatments. Steeping
      DDGS with FDE-A had lower (P = 0.01) ATTD of NDF than control but higher (P =
      0.001) ATTD of crude fat compared with the control or DDGS steeped with FDE-B.
      Values for DE content in steeped DDGS were not different (P > 0.05) and amounted
      to 4,095, 4,039, and 3,974 kcal/kg DM for the control, FDE-A, and FDE-B,
      respectively. In conclusion, under conditions of the study, steeping DDGS with
      exogenous enzymes did not improve fiber and energy digestibility.

PMID- 29635414
TI  - The passage of tobacco control law 174 in Lebanon: reflections on the problem,
      policies and politics.
AB  - Progress in tobacco control policy making has occurred worldwide through advocacy
      campaigns involving multiple players- civil society groups, activists, academics,
      media and policymakers. The Framework Convention on Tobacco Control (FCTC)-the
      first ever global health treaty-outlines evidence-based tobacco control policies.
      Lebanon ratified the FCTC in 2005, but until 2011, tobacco control policies
      remained rudimentary and not evidence-based. Beginning in 2009, a concerted
      advocacy campaign was undertaken by a variety of stakeholders with the aim of
      accelerating the process of adopting a strong tobacco control policy. The
      campaign was successful, and Law 174 passed the Lebanese Parliament in August
      2011. In this article, we analyse the policy making process that led to the
      adoption of Law 174 using Kingdon's model. The analysis relies on primary and
      secondary data sources including historical records of key governmental
      decisions, documentation of the activities of the concerted advocacy campaign and
      in-depth interviews with key stakeholders. We describe the opening of a window of
      opportunity as a result of the alignment of the problem, policy and politics
      streams. Furthermore, findings revealed that despite the challenge of persistent
      tobacco industry interference and established power relations between the
      industry, its allies and policymakers; policy entrepreneurs succeeded in
      supporting the alignment of the streams, and influencing the passage of the law.
      Kingdon's multiple stream approach was useful in explaining how tobacco control
      became an emerging policy issue at the front of the policy agenda in Lebanon.

PMID- 29635410
TI  - Diagnosis and management of asymptomatic bacteriuria in kidney transplant
      recipients: a survey of current practice in Europe.
AB  - Background: Asymptomatic bacteriuria is frequent in kidney transplant recipients
      (KTRs). However, there is no consensus on diagnosis or management. We conducted a
      European survey to explore current practice related to the diagnosis and
      management of asymptomatic bacteriuria in adult KTRs. Methods: A panel of experts
      from the European Renal Association-European Dialysis Transplant
      Association/Developing Education Science and Care for Renal Transplantation in
      European States working group and the European Study Group for Infections in
      Compromised Hosts of the European Society of Clinical Microbiology and Infectious
      Diseases designed this cross-sectional, questionnaire-based, self-administered
      survey. Invitations to participate were e-mailed to European physicians involved
      in the care of KTRs. Results: Two hundred and forty-four participants from 138
      institutions in 25 countries answered the survey (response rate 30%). Most
      participants [72% (176/244)] said they always screen for asymptomatic bacteriuria
      in KTRs. Six per cent (15/240) reported never treating asymptomatic bacteriuria
      with antibiotics. When antimicrobial treatment was used, 24% of the participants
      (53/224) said they would start with empirical antibiotics. For an episode of
      asymptomatic bacteriuria caused by a fully susceptible microorganism and despite
      no contraindications, a majority of participants (121/223) said they would use a
      fluoroquinolone (n = 56), amoxicillin/clavulanic acid (n = 38) or oral
      cephalosporins (n = 27). Conclusions: Screening for and treating asymptomatic
      bacteriuria are common in KTRs despite uncertainties around the benefits and
      harms. In an era of antimicrobial resistance, further studies are needed to
      address the diagnosis and management of asymptomatic bacteriuria in these
      patients.

PMID- 29635415
TI  - Beyond the Biomedical: Preexposure Prophylaxis Failures in a Cohort of Young
      Black Men Who Have Sex With Men in Atlanta, Georgia.
AB  - Human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP) has high
      biomedical efficacy; however, awareness, access, uptake, and persistence on
      therapy remain low among black men who have sex with men (BMSM), who are at
      highest risk of HIV in the United States. To date, discussions of "PrEP failure"
      have focused on one typology: rare, documented HIV acquisitions among PrEP users
      with adequate serum drug levels (ie, biomedical failure). In our cohort of HIV
      negative young BMSM in Atlanta, Georgia, we continue to observe a high HIV
      incidence (6.2% annually at interim analysis) despite access to free PrEP
      services. Among 14 seroconversions, all were offered PrEP before acquiring HIV.
      Among these participants, we identified 4 additional typologies of PrEP failure
      that expand beyond biomedical failure: low PrEP adherence, PrEP discontinuation,
      PrEP contemplation without initiation, and PrEP refusal. We describe the 5
      typologies and suggest interventions to improve PrEP effectiveness among those at
      highest risk.

PMID- 29635416
TI  - New Methods for Inferring the Distribution of Fitness Effects for INDELs and
      SNPs.
AB  - Small insertions and deletions (INDELs; <=50 bp) are the most common type of
      variability after single nucleotide polymorphism (SNP). However, compared with
      SNPs, we know little about the distribution of fitness effects (DFE) of new INDEL
      mutations and how prevalent adaptive INDEL substitutions are. Studying INDELs has
      been difficult partly because identifying ancestral states at these sites is
      error-prone and misidentification can lead to severely biased estimates of the
      strength of selection. To solve these problems, we develop new maximum likelihood
      methods, which use polymorphism data to simultaneously estimate the DFE, the
      mutation rate, and the misidentification rate. These methods are applicable to
      both INDELs and SNPs. Simulations show that they can provide highly accurate
      results. We applied the methods to an INDEL polymorphism data set in Drosophila
      melanogaster. We found that the DFE for polymorphic INDELs in protein-coding
      regions is bimodal, with the variants being either nearly neutral or strongly
      deleterious. Based on the DFE, we estimated that 71.5-83.7% of the INDEL
      substitutions that took place along the D. melanogaster lineage were fixed by
      positive selection, which is comparable with the prevalence of adaptive
      substitutions at nonsynonymous sites. The new methods have been implemented in
      the software package anavar.

PMID- 29635417
TI  - Quality of cross-infection control in dental laboratories. A critical systematic
      review.
AB  - Purpose: To identify reported practices for cross-infection control in dental
      laboratories and to quantify the importance of the flaws encountered. Data
      sources: Systematic search (cross-infection AND dental laboratory) at EMBASE,
      PubMed, SciELO and Scopus databases. Study selection: Papers reporting on cross
      sectional studies providing original data about cross-infection knowledge,
      practices and attitudes of dental technicians. Papers reporting on a single
      laboratory or institution were excluded. Data extraction: Data extraction was
      undertaken independently by three reviewers using a purpose made form. The
      outcome of this study was analyzed in five aspects, namely process organization,
      disinfection, working environment, use of individual protective equipment and
      vaccination policy. Results of data synthesis: The systematic search output was
      1651 references and 11 papers were finally selected. Flaws were more frequently
      identified in terms of vaccination policy, biological safety of the working
      environment and use of individual protective equipment (100%). Slightly better
      results were found in terms of organization of the cross-infection control
      process (89.47%) and disinfection practices (85.71%). The application of the
      formula for disclosing the relative importance of the flaws identified in the
      literature prioritizes the need for interventions aimed at improving the
      organization of the cross-infection control procedures, followed by training in
      item disinfection. The control of the working environment together with the use
      of individual protective equipments rank closely in importance, followed by the
      existence of a vaccination policy. Conclusions: Sub-standard cross-contamination
      practices seem to be a common finding in dental laboratories, which may well
      compromise the quality of certain dental treatments.

PMID- 29635418
TI  - Dysglycaemia, Inflammation and Psychosis: Findings From the UK ALSPAC Birth
      Cohort.
AB  - Background: Psychosis is associated with both dysglycaemia and low-grade
      inflammation, but population-based studies investigating the interplay between
      these factors are scarce. Aims: (1) To explore the direction of association
      between markers of dysglycaemia, inflammation and psychotic experiences (PEs);
      and (2) To explore whether dysglycaemia moderates and/or mediates the association
      between inflammation and PEs. Method: Data from the Avon Longitudinal Study of
      Parents and Children (ALSPAC) birth cohort were modeled using logistic and linear
      regression to examine cross-sectional and longitudinal associations between
      markers of dysglycaemia (ages 9 and 18), interleukin-6 (IL-6) (age 9), and PEs
      (ages 12 and 18). We tested for an interaction between dysglycaemia and IL-6 on
      risk of PEs at age 18, and tested whether dysglycaemia mediated the relationship
      between IL-6 and PEs. Results: Based on 2627 participants, at age 18, insulin
      resistance (IR) was associated with PEs (adjusted OR = 2.32; 95% CI, 1.37-3.97).
      IR was associated with IL-6 both cross-sectionally and longitudinally.
      Interaction analyses under a multiplicative model showed that IR moderated the
      association between IL-6 at age 9 and PEs at age 18 (adjusted OR for interaction
      term = 2.18; 95% C.I., 1.06-4.49). Mediation analysis did not support a model of
      IR mediating the relationship between IL-6 and PEs. Implications: IR is
      associated with PEs in young people even before the onset of clinical psychosis.
      Metabolic alterations may interact with childhood inflammation to increase risk
      of PEs. The findings have implications for clinical practice and future research.

PMID- 29635419
TI  - BCG Vaccination at Birth and Rate of Hospitalization for Infection Until 15
      Months of Age in Danish Children: A Randomized Clinical Multicenter Trial.
AB  - Background: The bacillus Calmette-Guerin (BCG) vaccine against tuberculosis might
      reduce the non-tuberculosis-related child mortality rate in low-income settings.
      We tested the hypothesis that BCG vaccination at birth would reduce early
      childhood hospitalization for infection in Denmark, a high-income setting.
      Hospitalization for infection was a secondary outcome in a randomized trial with
      the primary aim to estimate the potential non-specific effects of BCG vaccination
      at birth on all-cause hospitalization. Methods: A total of 4262 children included
      in the Danish Calmette Study were assigned randomly to either receive the BCG
      vaccine or not and were followed through the Danish National Patient Register.
      The outcome was number of hospitalizations for infection until the age of 15
      months. Data were analyzed by Cox regression in intention-to-treat (ITT) and per
      protocol (PP) analyses. Results: In the ITT analysis, we observed 588
      hospitalizations for infection (mean, 0.28 hospitalization per child) among the
      2129 children allocated to receive the BCG vaccine and 595 hospitalizations for
      infection (mean, 0.28 hospitalization per child) among the 2133 children
      allocated to the control group (hazard ratio [HR], 0.99 [95% confidence interval
      (CI), 0.85-1.15]). The PP analysis yielded an HR of 1.00 (95% CI, 0.86-1.16).
      Predefined interaction ITT analyses showed that among 740 children with a BCG
      vaccinated mother, the HR for BCG-vaccinated children was 0.65 (95% CI, 0.45
      0.94); the HR for children who had a non-BCG-vaccinated mother was 1.10 (95% CI,
      0.93-1.29) (P = .01, test of no interaction). Cesarean delivery modified the
      effect of BCG vaccination (HRs, 0.73 [95% CI, 0.54-0.99] in children born by
      cesarean section vs 1.10 [95% CI, 0.92-1.30] in other children; P = .02). When
      the outcome was defined as time to first hospitalization, the HR for premature
      children after BCG vaccination was 1.81 (95% CI, 0.95-3.43), whereas the HR was
      0.94 (95% CI, 0.82-1.08) for children born at term (P = .05). Conclusion: BCG
      vaccination did not affect the rate of hospitalization for infection up to the
      age of 15 months in Danish children. In future studies, the role of maternal BCG
      vaccination, premature birth, and cesarean delivery needs further exploration.

PMID- 29635420
TI  - Validation of a biomarker panel in Barrett's esophagus to predict progression to
      esophageal adenocarcinoma.
AB  - In a prior study, baseline mutational load (ML) predicted progression to high
      grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) in Barrett's esophagus
      (BE) with an area under the curve (AUC) of 0.95. We aimed to validate the test
      characteristics of this predictive biomarker panel using crude DNA lysates in a
      larger well-characterized cohort. We performed a nested case-control study of BE
      patients from three tertiary referral centers in the Netherlands. Cases had
      baseline nondysplastic BE (NDBE) and developed HGD/EAC >= 2 years later. Controls
      were matched 2:1, had baseline NDBE, and no progression. Polymerase chain
      reaction (PCR)-based mutational analysis was performed on crude lysates from
      formalin-fixed, paraffin-embedded tissue. ML was calculated from loss of
      heterozygosity (LOH) and microsatellite instability (MSI) at 10 genomic loci.
      Receiver operator characteristic (ROC) curves were created to assess the
      diagnostic utility of various cutoffs of ML for progression. Of 159 subjects, 58
      were progressors and 101 were nonprogressors, there was no difference in mean ML
      in preprogression tissue in progressors and nonprogressors (ML = 0.73 +/- 0.69
      vs. ML = 0.74 +/- 0.61, P = 0.93). ROC curves showed poor discrimination of ML in
      predicting progression with AUC of 0.50 at ML >= 1. AUC did not vary with
      different ML cut-points. The utility of the ML to stratify BE patients for risk
      of progression was not confirmed in this study. The etiology for discrepancies
      between this and prior studies showing high predictiveness is likely due to the
      use of crude lysates in this study, but requires further investigation.

PMID- 29635421
TI  - Prospective association between added sugars and frailty in older adults.
AB  - Background: Sugar-sweetened beverages and added sugars (monosaccharides and
      disaccharides) in the diet are associated with obesity, diabetes, and
      cardiovascular disease, which are all risk factors for decline in physical
      function among older adults. Objective: The aim of this study was to examine the
      association between added sugars in the diet and incidence of frailty in older
      people. Design: Data were taken from 1973 Spanish adults >=60 y old from the
      Seniors-ENRICA cohort. In 2008-2010 (baseline), consumption of added sugars
      (including those in fruit juices) was obtained using a validated diet history.
      Study participants were followed up until 2012-2013 to assess frailty based on
      Fried's criteria. Statistical analyses were performed with logistic regression
      adjusted for age, sex, education, smoking status, body mass index, energy intake,
      self-reported comorbidities, Mediterranean Diet Adherence Score (excluding
      sweetened drinks and pastries), TV watching time, and leisure-time physical
      activity. Results: Compared with participants consuming <15 g/d added sugars
      (lowest tertile), those consuming >=36 g/d (highest tertile) were more likely to
      develop frailty (OR: 2.27; 95% CI: 1.34, 3.90; P-trend = 0.003). The frailty
      components "low physical activity" and "unintentional weight loss" increased dose
      dependently with added sugars. Association with frailty was strongest for sugars
      added during food production. Intake of sugars naturally appearing in foods was
      not associated with frailty. Conclusions: The consumption of added sugars in the
      diet of older people was associated with frailty, mainly when present in
      processed foods. The frailty components that were most closely associated with
      added sugars were low level of physical activity and unintentional weight loss.
      Future research should determine whether there is a causal relation between added
      sugars and frailty.

PMID- 29635423
TI  - Higher incidence of screening-related cancers in the employed population.
AB  - Background: Employment may confound the risk of a cancer diagnosis in both
      directions. We hypothesized that a higher baseline rate of employment among
      cancer patients may explain the lack of association between a cancer diagnosis
      and later unemployment in many studies. Aims: To assess the unemployment rate
      among cancer patients before diagnosis compared with a matched cancer-free
      control group. Methods: Using data from the Israeli National Central Bureau of
      Statistics 1995 census (persons aged between 15 and 60 years old), the Israeli
      Tax Authority database and the Israel Cancer Registry, cancer patients (diagnosed
      between the years 2000 and 2007 and alive at 2011) were compared with matched
      cancer-free controls. Results: There were 8797 cancer patients and 26166 cancer
      free controls. We found that, in general, cancer was not associated with
      unemployment 2 years before diagnosis (adjusted odds ratio [OR] = 0.96, 95%
      confidence interval [CI] 0.90-1.009, P = NS) after adjustment for age, gender,
      ethnicity, educational years and residential socioeconomic position. However, the
      diagnoses associated with screening (breast, prostate, colorectal and cervix
      cancers) were inversely associated with unemployment 2 years before diagnosis
      (adjusted OR = 0.90, 95% CI 0.84-0.97, P < 0.01). Conclusions: The results from
      the current study suggest that a higher baseline rate of employment among cancer
      patients, mainly those who were diagnosed with screening-associated cancers,
      explains false negative results in previous studies assessing cancer survivors'
      work issues.

PMID- 29635422
TI  - Characterization of poxtA, a novel phenicol-oxazolidinone-tetracycline resistance
      gene from an MRSA of clinical origin.
AB  - Objectives: To characterize a novel phenicol-oxazolidinone-tetracycline
      resistance gene, named poxtA, identified in a previously described MRSA strain
      that was highly resistant to linezolid and also carried the cfr gene. Methods:
      The poxtA gene was identified by bioinformatic analysis of the whole genome
      sequence of Staphylococcus aureus AOUC-0915. The poxtA gene was cloned in a
      shuttle plasmid vector and expressed in Escherichia coli, S. aureus and
      Enterococcus faecalis to investigate the protein function. Comparative sequence
      analyses at the protein and genetic levels were carried out using standard
      procedures. Results: The poxtA gene encodes a protein that is 32% identical to
      OptrA and exhibits structural features typical of the F lineage of the ATP
      binding cassette (ABC) protein superfamily that cause antibiotic resistance by
      ribosomal protection. Expression of poxtA in E. coli, S. aureus and E. faecalis
      was able to decrease susceptibility to phenicols, oxazolidinones and
      tetracyclines. A database search identified the presence of poxtA in E. faecalis,
      Enterococcus faecium and Pediococcus acidilactici strains, mostly of animal
      origin, and revealed the presence of poxtA homologues in the genomes of some
      Clostridiales. Analysis of the genetic context revealed that poxtA was located in
      a composite transposon-like structure containing two IS1216 elements.
      Conclusions: A novel resistance gene, named poxtA, encoding a protein of the
      antibiotic resistance (ARE) ABC-F lineage, was identified in the genome of an
      MRSA of clinical origin. PoxtA can confer decreased susceptibility to phenicols,
      oxazolidinones and tetracyclines and is associated with a putative mobile element
      that could contribute to its horizontal dissemination.

PMID- 29635424
TI  - Breast Implant-Associated Anaplastic Large Cell Lymphoma With Bone Marrow
      Involvement.
AB  - Level of Evidence 5: 

PMID- 29635425
TI  - Parental Unemployment and Offspring Psychotropic Medication Purchases: A
      Longitudinal Fixed-Effects Analysis of 138,644 Adolescents.
AB  - Parental unemployment is associated with worse adolescent mental health, but
      prior evidence has primarily been based on cross-sectional studies subject to
      reverse causality and confounding. We assessed the association between parental
      unemployment and changes in adolescent psychotropic medication purchases, with
      longitudinal individual-level fixed-effects models that controlled for time
      invariant confounding. We used data from a large, register-based panel of Finnish
      adolescents aged 13-20 years in 1987-2012 (n = 138,644) that included annual
      measurements of mothers' and fathers' employment and offspring psychotropic
      medication purchases. We assessed changes in the probability of adolescent
      psychotropic medication purchases in the years before, during, and after the
      first episode of parental unemployment. There was no association between mother's
      unemployment and offspring psychotropic purchases in the fixed-effects models,
      suggesting this association is largely driven by unmeasured confounding and
      selection. By contrast, father's unemployment led to a significant 15%-20%
      increase in the probability of purchasing psychotropic medication among
      adolescents even after extensive controls for observed and unobserved
      confounding. This change takes at least 1 year to emerge, but it is long-lasting;
      thus, policies are needed that mitigate the harm of father's unemployment on
      offspring's mental well-being.

PMID- 29635426
TI  - Human alpha-defensin-1 protects cells from intoxication with Clostridium
      perfringens iota toxin.
AB  - Iota toxin is produced by Clostridium perfringens type E strains and associated
      with diarrhea in cattle and lambs. This binary protein toxin comprises the enzyme
      component iota a (Ia), which ADP-ribosylates G-actin, and the separate transport
      component iota b (Ib), which delivers Ia into the cytosol of target cells. Ib
      binds to cell receptors and forms biologically active toxin complexes with Ia,
      which cause rounding of adherent cells due to the destruction of the actin
      cytoskeleton. Here, we report that the human peptide alpha-defensin-1 protects
      cultured cells including human colon cells from intoxication with iota toxin. In
      contrast, the related beta-defensin-1 had no effect, indicating a specific mode
      of action. The alpha-defensin-1 did not inhibit ADP-ribosylation of actin by Ia
      in vitro. Pretreatment of Ib with alpha-defensin-1 prior to addition of Ia
      prevented intoxication. Additionally, alpha-defensin-1 protected cells from
      cytotoxic effects mediated by Ib in the absence of Ia, implicating that alpha
      defensin-1 interacts with Ib to prevent the formation of biologically active iota
      toxin on cells. In conclusion, the findings contribute to a better understanding
      of the functions of alpha-defensin-1 and suggest that this human peptide might be
      an attractive starting point to develop novel pharmacological options to
      treat/prevent diseases associated with iota toxin-producing Clostridium
      perfringens strains.

PMID- 29635427
TI  - Caregiver-Reported Indicators of Communication and Social Functioning for Young
      Children Who Are Deaf or Hard of Hearing.
AB  - We elicited caregiver-reported observations of children aged 5-10 who were deaf
      or hard of hearing (DHH) that resulted in two age-specific instruments: Caregiver
      Report of Behaviors and Events (CROBE-DHH 5-7 and 8-10). These new instruments
      record observations on communication and social behaviors/events. In Study 1, 36
      caregivers provided qualitative data on important content on what they were able
      to observe for instrument development and in Study 2, 271 provided data for
      studying cross-sectional measurement properties. Two modules resulted in 11 items
      for children age 5-7 and 15 items for children 8-10 years. Items showing good 7
      day reproducibility (ICC over .70) and fair 4-week reproducibility (ICC over .50)
      were retained. Children with milder hearing loss received higher (better) scores.
      Items did not distinguish between those with or without cochlear implants.
      Analyses suggest that the instruments are best used as individual indicator
      items. In both age groups, caregivers reported youths missed out on family
      conversations and spent little time on their own. These content-validated
      indicators apply to all children with DHH. Further work will evaluate the
      usefulness of these indicators in evaluating change in communication and social
      behaviors, and the implications of results for intervention.

PMID- 29635429
TI  - Spatiotemporal dynamics of human leptospirosis and its relationship with rainfall
      anomalies in Colombia.
AB  - Background: In Colombia, human leptospirosis (HL) is a disease that has had a
      mandatory notification rule since 2007. Humans usually acquire the infection
      through water contaminated with animal urine that comes into direct contact with
      cutaneous lesions, eyes or mucous membranes. Objectives: To analyze the
      spatiotemporal variability in the occurrence of HL cases in Colombia between 2007
      and 2016, and its relation with the El Nino Southern Oscillation (ENSO) cycle and
      the consequent anomalies in rainfall in spatiotemporal clusters. Methods: An
      ecological study of the HL cases, aggregated by municipality, and reported
      between 2007 and 2016, is presented. Findings: During the period of study, 9928
      cases of HL were reported, and 58.9% of the municipalities reported at least one
      case of leptospirosis. Six spatiotemporal clusters were identified-five were in
      the Andean region and one was in the Caribbean region. The assessment of the ENSO
      cycle and rainfall anomalies suggests the importance of La Nina episodes, and
      excess rainfall periods in the occurrence of cases of HL. Conclusions: Our
      results demonstrate the importance of the ENSO cycle, rainfall periods and
      periods with excess rainfall in the occurrence of cases and outbreaks of HL in
      Colombia, and suggest the importance of the topography of valleys and flood zones
      as zones in which the risk of infection is elevated.

PMID- 29635430
TI  - Knockout of the Gnrh genes in zebrafish: effects on reproduction and potential
      compensation by reproductive and feeding-related neuropeptides.
AB  - Gonadotropin-releasing hormone (GNRH) is known as a pivotal upstream regulator of
      reproduction in vertebrates. However, reproduction is not compromised in the
      hypophysiotropic Gnrh3 knockout line in zebrafish (gnrh3-/-). In order to
      determine if Gnrh2, the only other Gnrh isoform in zebrafish brains, is
      compensating for the loss of Gnrh3, we generated a double Gnrh knockout zebrafish
      line. Surprisingly, the loss of both Gnrh isoforms resulted in no major impact on
      reproduction, indicating that a compensatory response, outside of the Gnrh
      system, was evoked. A plethora of factors acting along the reproductive
      hypothalamus-pituitary axis were evaluated as possible compensators based on
      neuroanatomical and differential gene expression studies. In addition, we also
      examined the involvement of feeding factors in the brain as potential
      compensators for Gnrh2, which has known anorexigenic effects. We found that the
      double knockout fish exhibited upregulation of several genes in the brain,
      specifically gonadotropin-inhibitory hormone (gnih), secretogranin 2 (scg2),
      tachykinin 3a (tac3a), and pituitary adenylate cyclase-activating peptide 1
      (pacap1), and downregulation of agouti-related peptide 1 (agrp1), indicating the
      compensation occurs outside of Gnrh cells and therefore is a noncell autonomous
      response to the loss of Gnrh. While the differential expression of gnih and agrp1
      in the double knockout line was confined to the periventricular nucleus and
      hypothalamus, respectively, the upregulation of scg2 corresponded with a broader
      neuronal redistribution in the lateral hypothalamus and hindbrain. In conclusion,
      our results demonstrate the existence of a redundant reproductive regulatory
      system that comes into play when Gnrh2 and Gnrh3 are lost.

PMID- 29635428
TI  - Inverse correlation between vascular endothelial growth factor back-filtration
      and capillary filtration pressures.
AB  - Background: Vascular endothelial growth factor A (VEGF) is an essential growth
      factor during glomerular development and postnatal homeostasis. VEGF is secreted
      in high amounts by podocytes into the primary urine, back-filtered across the
      glomerular capillary wall to act on endothelial cells. So far it has been assumed
      that VEGF back-filtration is driven at a constant rate exclusively by diffusion.
      Methods: In the present work, glomerular VEGF back-filtration was investigated in
      vivo using a novel extended model based on endothelial fenestrations as surrogate
      marker for local VEGF concentrations. Single nephron glomerular filtration rate
      (SNGFR) and/or local filtration flux were manipulated by partial renal mass
      ablation, tubular ablation, and in transgenic mouse models of systemic or
      podocytic VEGF overexpression or reduction. Results: Our study shows positive
      correlations between VEGF back-filtration and SNGFR as well as effective
      filtration rate under physiological conditions along individual glomerular
      capillaries in rodents and humans. Conclusion: Our results suggest that an
      additional force drives VEGF back-filtration, potentially regulated by SNGFR.

PMID- 29635431
TI  - Does BCG Vaccination Protect Against Nontuberculous Mycobacterial Infection? A
      Systematic Review and Meta-Analysis.
AB  - Background: The incidence of nontuberculous mycobacterial (NTM) infections is
      increasing worldwide, particularly NTM lymphadenitis and skin infections (Buruli
      ulcer). This review summarizes the evidence for the protective effectiveness of
      BCG vaccination against NTM disease. Methods: A systematic search using PRISMA
      guidelines was done for controlled studies investigating the protective
      effectiveness of BCG vaccination against NTM disease in immunocompetent
      individuals. This revealed 10 studies, including almost 12 million participants.
      Results: Three cohort studies in industrialized countries suggest that the
      incidence of NTM lymphadenitis is greatly reduced among BCG-vaccinated children
      compared with BCG-unvaccinated children, with a risk ratio (RR) of 0.04 (95%
      confidence interval [CI], .01-.21). In two randomized trials in low-income
      countries, BCG protected against Buruli ulcer for the first 12 months following
      vaccination (RR, 0.50 [95% CI, .37-.69]). Four case-control studies had
      conflicting results. One cohort study found that individuals with Buruli ulcer
      are less likely to develop osteomyelitis if they have a BCG scar (RR, 0.36 [95%
      CI, .22-.58]). No studies have compared different BCG vaccine strains or the
      effect of revaccination in this setting. Conclusions: The protective effect of
      BCG vaccination against NTM should be taken into consideration when deciding on
      recommendations for discontinuation of universal BCG vaccination programs and in
      assessing new vaccines designed to replace BCG.

PMID- 29635432
TI  - Absolute Lymphocyte Count: A Predictor of Recurrent Cytomegalovirus Disease in
      Solid Organ Transplant Recipients.
AB  - Background: Recurrent cytomegalovirus (CMV) disease in solid organ transplant
      recipients frequently occurs despite effective antiviral therapy. We previously
      demonstrated that patients with lymphopenia before liver transplantation are more
      likely to develop posttransplant infectious complications including CMV. The aim
      of this study was to explore absolute lymphocyte count (ALC) as a predictor of
      relapse following treatment for CMV disease. Methods: We performed a
      retrospective cohort study of heart, liver, and kidney transplant recipients
      treated for an episode of CMV disease. Our primary outcome was time to relapse of
      CMV within 6 months. Data on potential predictors of relapse including ALC were
      collected at the time of CMV treatment completion. Univariate and multivariate
      hazard ratios (HRs) were calculated with a Cox model. Multiple imputation was
      used to complete the data. Results: Relapse occurred in 33 of 170 participants
      (19.4%). Mean ALC in relapse-free patients was 1.08 +/- 0.69 vs 0.73 +/- 0.42 *
      103 cells/MUL in those who relapsed, corresponding to an unadjusted hazard ratio
      of 1.11 (95% confidence interval, 1.03-1.21; P = .009, n = 133) for every
      decrease of 100 cells/MUL. After adjusting for potential confounders, the
      association between ALC and relapse remained significant (HR, 1.11 [1.03-1.20]; P
      = .009). Conclusions: Low ALC at the time of CMV treatment completion was a
      strong independent predictor for recurrent CMV disease. This finding is
      biologically plausible given the known importance of T-cell immunity in
      maintaining CMV latency. Future studies should consider this inexpensive, readily
      available marker of host immunity.

PMID- 29635433
TI  - Green tea polyphenols enhance gingival keratinocyte integrity and protect against
      invasion by Porphyromonas gingivalis.
AB  - The gingival epithelium, a stratified squamous tissue that acts as an interface
      between the external environment and the underlying connective tissue, plays an
      active role in maintaining periodontal health. The aim of the present study was
      to investigate the ability of green tea catechins to enhance gingival epithelial
      barrier function and protect against the disruption of epithelial integrity
      induced by Porphyromonas gingivalis. Both the green tea extract and
      epigallocatechin-3-gallate (EGCG) dose- and time-dependently increased the
      transepithelial electrical resistance (TER) of a gingival keratinocyte model and
      decreased the permeability of the cell monolayer to fluorescein isothyocyanate
      conjugated 4.4-kDa dextran. This was associated with the increased expression of
      zonula occludens-1 (ZO-1) and occludin, two tight junction proteins. Treating the
      gingival keratinocyte monolayer with P. gingivalis caused a reduction in TER and
      affected the distribution of ZO-1 and occludin, allowing P. gingivalis to
      translocate through the cell monolayer. These deleterious effects mediated by P.
      gingivalis were abolished by the green tea extract and EGCG. This protection may
      be in part related to the ability of tea catechins to inhibit the protease
      activities of P. gingivalis. Given the above properties, green tea catechins may
      represent promising preventive and therapeutic molecules against periodontal
      disease.

PMID- 29635435
TI  - Axillo-iliac artery bypass for recurrent aortic coarctation to reduce cardiac
      afterload.
AB  - A 13-year-old girl, who had undergone interrupted aortic arch repair with an 8-mm
      graft as a neonate and Fontan completion in childhood, developed ventricular
      fibrillation due to long-QT syndrome. Cardioverter defibrillator implantation was
      planned. Preoperative catheterization showed a 45-mmHg aortic pressure gradient
      and ventricular end-diastolic pressure of 11 mmHg. This indicated that recurrent
      coarctation had adversely affected ventricular function. After consideration of
      the patient's age, symptoms and anatomical/surgical complexities, axillo-iliac
      bypass with cardioverter defibrillator implantation was performed. Postoperative
      ventricular end-diastolic pressure was 6 mmHg. Axillo-iliac bypass is a surgical
      option for coarctation that can reduce cardiac afterload.

PMID- 29635434
TI  - Fatigue Related to Speech Processing in Children With Hearing Loss: Behavioral,
      Subjective, and Electrophysiological Measures.
AB  - Purpose: The purpose of this study was to examine fatigue associated with
      sustained and effortful speech-processing in children with mild to moderately
      severe hearing loss. Method: We used auditory P300 responses, subjective reports,
      and behavioral indices (response time, lapses of attention) to measure fatigue
      resulting from sustained speech-processing demands in 34 children with mild to
      moderately severe hearing loss (M = 10.03 years, SD = 1.93). Results: Compared to
      baseline values, children with hearing loss showed increased lapses in attention,
      longer reaction times, reduced P300 amplitudes, and greater reports of fatigue
      following the completion of the demanding speech-processing tasks. Conclusions:
      Similar to children with normal hearing, children with hearing loss demonstrate
      reductions in attentional processing of speech in noise following sustained
      speech-processing tasks-a finding consistent with the development of fatigue.

PMID- 29635436
TI  - Validated HPTLC Method for Dihydrokaempferol-4'-O-glucopyranoside Quantitative
      Determination in Alcea Species.
AB  - Dihydrokaempferol-4'-O-glucopyranoside, a flavanonol glucoside, is the major
      compound in the flower of Alcea rosea L. which possesses significant antioxidant
      and anticancer activity against HepG-2 cell line and thus can be considered a
      marker compound for A. rosea L. We attempted to establish a new simple, validated
      high-performance thin-layer chromatographic (HPTLC) method for the quantitation
      of dihydrokaempferol-4'-O-glucopyranoside to help in the standardization of the
      hydroalcoholic extracts of A. rosea L. flowers and to evaluate the best method
      for its extraction from the plant material. The separation was carried out on an
      HPTLC aluminum plate pre-coated with silica gel 60F-254, eluted with ethyl
      acetate-methanol-water-acetic acid (30:5:4:0.15 v/v). Densitometric scanning was
      performed using a Camag TLC scanner III, at 295 nm. A linear relationship was
      obtained between the concentrations (0.9-3.6 mg) and peak areas with the
      correlation coefficient (r) of 0.9971 +/- 0.0002. The percentage relative
      standard deviations of intra-day and inter-day precisions were 0.22-1.45 and 0.49
      1.66, respectively. The percentage w/w of dihydrokaempferol-4'-O-glucopyranoside
      in the flowers of A. rosea L. after maceration and sonication for 15 min was
      found to be 0.733 g/100 g and 0.928 g/100 g, respectively.

PMID- 29635437
TI  - A 5-Year Prospective Multicenter Evaluation of Influenza Infection in Transplant
      Recipients.
AB  - Background: Seasonal influenza infection may cause significant morbidity and
      mortality in transplant recipients. The purpose of this study was to assess the
      epidemiology of symptomatic influenza infection posttransplant and determine risk
      factors for severe disease. Methods: Twenty centers in the United States, Canada,
      and Spain prospectively enrolled solid organ transplant (SOT) or hematopoietic
      stem cell transplant (HSCT) recipients with microbiologically confirmed influenza
      over 5 consecutive years (2010-2015). Demographics, microbiology data, and
      outcomes were collected. Serial nasopharyngeal swabs were collected at diagnosis
      and upto 28 days, and quantitative polymerase chain reaction for influenza A was
      performed. Results: We enrolled 616 patients with confirmed influenza (477 SOT;
      139 HSCT). Pneumonia at presentation was in 134 of 606 (22.1%) patients.
      Antiviral therapy was given to 94.1% for a median of 5 days (range, 1-42 days);
      66.5% patients were hospitalized and 11.0% required intensive care unit (ICU)
      care. The receipt of vaccine in the same influenza season was associated with a
      decrease in disease severity as determined by the presence of pneumonia (odds
      ratio [OR], 0.34 [95% confidence interval {CI}, .21-.55], P < .001) and ICU
      admission (OR, 0.49 [95% CI, .26-.90], P = .023). Similarly, early antiviral
      treatment (within 48 hours) was associated with improved outcomes. In patients
      with influenza A, pneumonia, ICU admission, and not being immunized were also
      associated with higher viral loads at presentation (P = .018, P = .008, and P =
      .024, respectively). Conclusions: Annual influenza vaccination and early
      antiviral therapy are associated with a significant reduction in influenza
      associated morbidity, and should be emphasized as strategies to improve outcomes
      of transplant recipients.

PMID- 29635438
TI  - Neoadjuvant chemotherapy followed by chemoradiation and surgery with and without
      cetuximab in patients with resectable esophageal cancer: a randomized, open
      label, phase III trial (SAKK 75/08).
AB  - Background: This open-label, phase III trial compared chemoradiation followed by
      surgery with or without neoadjuvant and adjuvant cetuximab in patients with
      resectable esophageal carcinoma. Patients and methods: Patients were randomly
      assigned (1 : 1) to two cycles of chemotherapy (docetaxel 75 mg/m2, cisplatin 75
      mg/m2) followed by chemoradiation (45 Gy, docetaxel 20 mg/m2 and cisplatin 25
      mg/m2, weekly for 5 weeks) and surgery, with or without neoadjuvant cetuximab 250
      mg/m2 weekly and adjuvant cetuximab 500 mg/m2 fortnightly for 3 months. The
      primary end point was progression-free survival (PFS). Results: In total, 300
      patients (median age, 61 years; 88% male; 63% adenocarcinoma; 85% cT3/4a, 90%
      cN+) were assigned to cetuximab (n = 149) or control (n = 151). The R0-resection
      rate was 95% for cetuximab versus 97% for control. Postoperative treatment
      related mortality was 6% in both arms. Median PFS was 2.9 years [95% confidence
      interval (CI), 2.0 to not reached] with cetuximab and 2.0 years (95% CI, 1.5-2.8)
      with control [hazard ratio (HR), 0.79; 95% CI, 0.58-1.07; P = 0.13]. Median
      overall survival (OS) time was 5.1 years (95% CI, 3.7 to not reached) versus 3.0
      years (95% CI, 2.2-4.2) for cetuximab and control, respectively (HR, 0.73; 95%
      CI, 0.52-1.01; P = 0.055). Time to loco-regional failure after R0-resection was
      significantly longer for cetuximab (HR 0.53; 95% CI, 0.31-0.90; P = 0.017); time
      to distant failure did not differ between arms (HR, 1.01; 95% CI, 0.64-1.59, P =
      0.97). Cetuximab did not increase adverse events in neoadjuvant or postoperative
      settings. Conclusion: Adding cetuximab to multimodal therapy significantly
      improved loco-regional control, and led to clinically relevant, but not
      significant improvements in PFS and OS in resectable esophageal carcinoma.
      Clinical trial information: NCT01107639.

PMID- 29635439
TI  - Novel bacterial diversity is enriched with chloroperoxidase-reacted organic
      matter under anaerobic conditions.
AB  - Fungal chloroperoxidases (CPOs) are one class of enzymes that produce natural
      organochlorides in soils. The microbial degradation of these organochlorides is
      not well known, though has implications for bioremediation, microbial ecology and
      natural chlorine and carbon cycling. In this study, Illumina-based 16S rRNA gene
      sequencing and real-time quantitative PCR (qPCR) was used to characterize the
      bacterial community enriched from an amendment of organic matter reacted with CPO
      under conditions conducive towards chlorination (CPO-OM). In total, 17 bacterial
      groups were enriched in triplicate microcosms inoculated with creek sediment and
      amended with CPO-OM. These bacterial groups were neither enriched with amendments
      of non-reacted organic matter extract, with or without oxidative stress induced
      by H2O2, nor with amendments of organic matter reacted with CPO under non
      chlorinating conditions. Of these, only two represented genera with known
      organohalide respiring bacteria-Dehalogenimonas and Dehalobacter. The genus
      Acetobacterium was also found to be enriched but the other 14 groups of enriched
      bacteria do not currently have any close phylogenetically related isolates. This
      study highlights a gap in the current understanding of the microbiology involved
      in natural organochloride turnover and suggests that CPO-OM could be used for
      isolating and culturing strains from novel bacteria genera.

PMID- 29635440
TI  - Neighborhood stress and autonomic nervous system activity during sleep.
AB  - Study Objectives: Stressful neighborhood environments are known to adversely
      affect health and contribute to health disparities but underlying mechanisms are
      not well understood. Healthy sleep can provide a respite from sustained
      sympathetic nervous system (SNS) activity. Our objective was to evaluate
      relationships between neighborhood stress and nocturnal and daytime SNS and
      parasympathetic nervous system (PNS) activity. Methods: Eighty-five urban
      residing African Americans (56.5% female; mean age of 23.0) participated.
      Evaluation included surveys of neighborhood stress and sleep-related vigilance,
      and continuous electrocardiogram (ECG) and actigraphic recording in participants'
      homes from which heart rate variability (HRV) analysis for low frequency/high
      frequency (LF/HF) ratio and normalized high frequency (nHF), as indicators of SNS
      and PNS activity, respectively, and total sleep time (TST), and wake after sleep
      onset were derived. Results: All significant relationships with HRV measures were
      from the sleep period. Neighborhood disorder correlated negatively with nHF (r = 
      .24, p = .035). There were also significant correlations of HRV indices with
      sleep duration and sleep fears. Among females, LF/HF correlated with exposure to
      violence, r = .39, p = .008, and nHF with census tract rates for violent crime (r
      = -.35, p = .035). In a stepwise regression, TST accounted for the variance
      contributed by violent crime to nHF in the female participants. Conclusions:
      Further investigation of relationships between neighborhood environments and
      SNS/PNS balance during sleep and their consequences, and strategies for
      mitigating such effects would have implications for health disparities.

PMID- 29635441
TI  - Twenty Thousand Needles Under the Sea. Trigger Point Dry Needling Aboard an
      Israeli Navy Submarine: A Case Report.
AB  - Nonspecific lower back pain affects a major part of the population at a certain
      point of their life. The intensity of pain can be debilitating and it causes a
      significant burden on society. Trigger point dry needling is a method of
      alleviating such pain by the introduction of needles into trigger points in
      muscles. A growing body of evidence supports its use in myofascial pain and
      specifically lower back pain. Submarine Medicine is a unique field due to the
      special characteristics and the environment of the submarine. It poses challenges
      that are not always seen by primary care physicians. Here, we present a case of a
      40-yr-old senior submarine officer who complained of pain in his lower back and
      pelvis before departing on a mission. The pain persisted in spite of treatment
      with nonsteroidal anti-inflammatory drugs and he was then treated by the
      submarine's physician with trigger point dry needling. The officer showed rapid
      improvement following this treatment, both regarding pain and the range of
      motion.

PMID- 29635443
TI  - Commentary on: Patients' and Surgeons' Perceptions of Social Media's Role in the
      Decision Making for Primary Aesthetic Breast Augmentation.

PMID- 29635442
TI  - Systemic-to-pulmonary artery shunting using heparin-bonded grafts.
AB  - OBJECTIVES: Systemic-to-pulmonary artery shunting remains an important palliative
      procedure in the staged management of complex congenital heart defects. The use
      of heparin-bonded polytetrafluoroethylene shunts (HBPSs) should enhance graft
      patency. This study aimed to review the single-centre experience using HBPS in
      the context of congenital cardiac surgery. METHODS: The records of 51 patients
      treated using HBPS between 2010 and 2016 were retrospectively reviewed. The
      median age and weight of the patients were 8 (range 3-83) days and 3.2 (range 1.8
      5.7) kg, respectively. Selected shunt size was 3.5 mm in all patients. Fourteen
      (27.5%) patients were planned for future biventricular repair and 37 (72.5%)
      patients underwent univentricular pathway. Shunt modifications included central
      aortopulmonary shunts (n = 35; 68.6%) and modified Blalock-Taussig shunts (n =
      16; 31.4%). Shunt patency and survival until estimated 2nd procedure were
      calculated using the Kaplan-Meier method. RESULTS: Shunt patency was 90 +/- 4%
      after a median duration of 133 (range 0-315) days. Early mortality (30 days) was
      3.9% (n = 2). Another 3 patients died during their hospital stay. All the
      deceased patients had univentricular morphology, and the cause of death was not
      shunt related in all patients. Five patients developed subtotal HBPS thrombosis
      intraoperatively (n = 3), early postoperatively after 3 days (n = 1, 1.9%) or
      late after 41 days (n = 1, 1.9%). Treatment of those patients comprised right
      ventricular outflow tract opening (n = 2, 3.9%) or new shunting (n = 3, 5.9%).
      Elective shunt takedown was performed during corrective surgery (n = 10, 19.6%),
      bidirectional Glenn (n = 25, 49%) or shunt replacement (n = 5, 9.8%). At the end
      of follow-up, 1 (1.9%) patient had still an HBPS in situ. The survival rate until
      planned 2nd procedure was 87 +/- 6% in univentricular patients and 100% in
      biventricular patients (P = 0.17). CONCLUSIONS: The use of HBPS in the context of
      palliative heart surgery is safe and seems to warrant a long-term patency of
      systemic-to-pulmonary shunts. However, by acting on only 1 site of Virchow's
      triad, shunt thrombosis, occurring predominantly early, cannot be totally
      excluded.

PMID- 29635444
TI  - Parental Incarceration and Child Health in the United States.
AB  - Mass incarceration has profoundly restructured the life courses of not only
      marginalized adult men for whom this event is now so prevalent but also their
      families. We examined research published from 2000 to 2017 on the consequences of
      parental incarceration for child health in the United States. In addition to
      focusing on specific health outcomes, we also considered broader indicators of
      child well-being because there has been little research on the association
      between parental incarceration and objectively measured child health outcomes.
      Our findings support 4 conclusions. First, paternal incarceration is negatively
      associated-possibly causally so-with a range of child health and well-being
      indicators. Second, although some research has suggested a negative association
      between maternal incarceration and child health, the evidence on this front is
      mixed. Third, although the evidence for average effects of paternal incarceration
      on child health and well-being is strong, research has also suggested that some
      key factors moderate the association between paternal incarceration and child
      health and well-being. Finally, because of the unequal concentration of parental
      incarceration and the negative consequences this event has for children, mass
      incarceration has increased both intracountry inequality in child health in the
      United States and intercountry inequality in child health between the United
      States and other developed democracies. In light of these important findings,
      investment in data infrastructure-with emphasis on data sets that include
      reliable measures of parental incarceration and child health and data sets that
      facilitate causal inferences-is needed to understand the child health effects of
      parental incarceration.

PMID- 29635445
TI  - GntR is involved in the expression of virulence in strain Streptococcus suis
      P1/7.
AB  - Streptococcus suis is a severe zoonotic pathogen, responsible for acute diseases
      in pigs and human. GntR proteins are widely distributed in various bacterial
      species. In a previous study, GntR proteins were reported to be involved in
      virulence in many pathogens. To investigate the relationship between GntR and S.
      suis serotype 2, we constructed an isogenic deletion mutant P1/7DeltagntR and an
      isogenic single-nucleotide substitution mutant P1/7gntR(SC070731), which took
      strain P1/7 as parent. The results show that the mutants P1/7DeltagntR and
      P1/7gntR(SC070731) have a stronger ability to tolerate oxidative stress and to
      reproduce in blood. Moreover, a higher fatality rate was observed in mice when
      challenged with P1/7DeltagntR or P1/7gntR(SC070731) compared with that of P1/7.
      Overall, all results suggest that GntR greatly impacts the virulence of S. suis
      serotype 2 strain P1/7 and give a new perspective on virulence generation in S.
      suis.

PMID- 29635446
TI  - Resistance of Selected Sorghum Genotypes to Maize Weevil (Coleoptera:
      Curculionidae).
AB  - The maize weevil, Sitophilus zeamais (Motschulsky) (Coleoptera: Curculionidae),
      is a major insect pest of stored grain. This study evaluated resistance of grain
      of 26 sorghum genotypes, Sorghum bicolor (L.) Moench, to maize weevil under
      laboratory conditions. Three female and two male newly emerged maize weevils were
      reared with 5 g of grain in each of 10 vials for each of the 26 sorghum genotypes
      in a laboratory experiment. The weevils and grain of each genotype were scored
      once every 3 wk for a total of five times during 105 d. The numbers of live and
      newly emerged maize weevils, dead weevils from the initial population, damage
      score (scale of 1-5), and grain weight loss were used to indicate resistance. The
      least percentage weight loss of 23.9 and 24.1% was recorded for sorghum genotypes
      Sureno and (5BRON151*Tegemeo)-HG7, respectively. Genotypes B.HF8 and
      (A964*P850029)-HW6 had the most weight loss, 70.6 and 67.7%, at 105 d after
      infestation. Genotypes B.HF8 and (A964*P850029)-HW6 consistently exhibited the
      highest numbers of maize weevil, 63 and 84, per vial at 105 d after infestation.
      Sorghum genotypes Sureno, (SV1*Sima/IS23250)-LG15, (5BRON151*Tegemeo)-HG7, and
      (B35*B9501)-HD9 ranked among the top four genotypes with least damage rating more
      often than any other genotype across the five sampling dates. On the other hand,
      genotypes B.HF8, (A964*P850029)-HW6, (Segaolane*WM#322)LG2, and
      (Tx2880*(Tx2880*(Tx2864*(Tx436*(Tx2864*PI550607)))))-PR3-CM1 were more often
      ranked among the top four genotypes with the highest damage rating. Our results
      indicate that grain of genotype Sureno is most resistant to the maize weevil
      among screened genotypes.

PMID- 29635447
TI  - Psychosocial Predictors of Self-reported Medical Adherence in Patients With Heart
      Failure Over 6 Months: An Examination of the Influences of Depression, Self
      efficacy, Social Support, and Their Changes.
AB  - Background: Poor adherence to medical regimens is a serious problem that
      interferes with heart failure (HF) patients' disease management and contributes
      to poor clinical outcomes. Few prospective studies have examined the psychosocial
      predictors of adherence over time in HF patients. Purpose: This study examined
      the influences of depression, self-efficacy, social support, and their changes on
      self-reported medical adherence over 6 months in HF patients. Methods:
      Participants were 252 HF outpatients, among whom 168 completed follow-up
      assessments. Hierarchical multiple regression analyses were conducted to examine
      whether psychosocial variables and their changes prospectively predicted
      adherence at 6 months, after adjusting for baseline adherence, age, gender,
      ethnicity, marital status, education, HF severity, medical comorbidity, and
      mental health treatment. Results: Baseline self-efficacy (beta = .22, p < .05),
      increase in self-efficacy (beta = .34, p < .001), and decrease in depression
      (beta = -.15, p = .05) predicted improved adherence over 6 months, but social
      support did not. In the combined model that included all significant psychosocial
      predictors from previous analyses, baseline self-efficacy (beta = .37, p = .001)
      and its increase (beta = .35, p < .001) emerged as independent predictors of
      improved adherence at 6 months. Conclusions: Promoting self-efficacy and reducing
      depressive symptoms may be promising targets of behavioral interventions to
      facilitate long-term disease management in HF patients.

PMID- 29635449
TI  - The use of electronic consultations is associated with lower specialist referral
      rates: a cross-sectional study using population-based health administrative data.
AB  - Background: The referral-consultation process can be difficult to navigate.
      Electronic consultations (eConsults) can help streamline referrals by
      facilitating inter-provider communication. Objective: We evaluated the potential
      effect of eConsult on specialist referral rates in Ontario among family
      physicians providing comprehensive care. Methods: We conducted a retrospective
      1:3 matched cohort study examining total referrals and referrals to all available
      medical specialties from primary care providers between 1 April 2014 and 31 March
      2015. We used multivariable random effects Poisson regression analysis to compare
      referral rates between eConsult and non-eConsult users while adjusting for
      relevant patient and provider characteristics. Referral rates were expressed per
      physician, per 100 patients and per 100 patient encounters. Results: There were
      113197 referrals across all medical specialties made by 119 eConsult physicians
      and 352 matched controls. Referral rates per physician were significantly lower
      in the eConsult group for all specialty groupings [unadjusted rate ratio (RR) =
      0.87, 95% confidence interval (CI) = 0.80-0.95; adjusted RR = 0.92, 95% CI = 0.85
      1.00]. Referral rates per patient were lower among eConsult physicians
      (unadjusted RR = 0.91, 95% CI = 0.84-0.98) but this difference was not
      statistically significant after adjustment (adjusted RR = 0.96, 95% CI = 0.90
      1.02). No statistically significant difference was observed when referrals were
      expressed per 100 patient encounters. Conclusion: This is the first Canadian
      study to examine the potential effect of eConsult on overall referrals at a
      population level. Our findings demonstrate that using eConsult service is
      associated with fewer referrals from primary to specialist care, with
      considerable potential for cost savings to our single-payer system.

PMID- 29635450
TI  - Is there a relation between the time to ICSI and the reproductive outcomes?
AB  - STUDY QUESTION: Does time to ICSI affect reproductive outcomes? SUMMARY ANSWER:
      Biochemical and clinical pregnancy diminish progressively as time between oocyte
      pick up (OPU) and ICSI increases after fresh embryo transfer. WHAT IS KNOWN
      ALREADY: Appropriate oocyte cytoplasmic and nuclear maturation are of paramount
      importance to ensure an optimal embryonic developmental competence. While nuclear
      maturation is usually attained by the time an oocyte reaches OPU, cytoplasmic
      maturation cannot be readily assessed and might be incomplete. On the other hand,
      excessive in vitro culture of mature human oocytes can affect their
      ultrastructural characteristics and, in mice, induces alterations in gene
      expression and changes of chromatin and histone modification patterns. STUDY
      DESIGN, SIZE, DURATION: Retrospective consecutive cohort study including 1468
      ICSI cycles carried out in a single center between December 2012 and September
      2015. All cycles were with patient's own oocytes and fresh embryo transfer (ET).
      A radiofrequency-based system was used to record exact culture times, namely, OPU
      denudation (DN); DN-ICSI and OPU-ICSI. We analyzed the effect of total and
      partial time intervals between procedures, from OPU to ICSI, on fertilization
      rate and biochemical, clinical, ongoing pregnancy and live birth rates.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: Differences in laboratory times between
      positive and negative biochemical, clinical, ongoing pregnancies and birth
      results were tested by Mann-Whitney U test. The likelihood of positive clinical
      outcomes was further modeled by locally weighted scatterplot smoothing (LOWESS)
      regression and logistic regression, adjusting for woman's age and BMI, number of
      transferred embryos; mean embryo morphological score, sperm origin and status,
      and number of mature oocytes obtained at OPU. Effect of time on fertilization
      rate was modeled by Generalized Linear Modeling (GLM) and LOWESS regression. MAIN
      RESULTS AND THE ROLE OF CHANCE: The mean woman's age was 38.4 years (SD 4.6).
      Biochemical, clinical, ongoing pregnancy and live birth rates after the fresh ET
      were: 39.6, 33.1, 25.7 and 20.8%, respectively. Cumulative values for biochemical
      pregnancy and live birth were 46.4 and 26.3%, respectively. Mean times in hours
      for OPU-DN, DN-ICSI and OPU-ICSI were: 1.00 (SD 0.20); 3.86 (SD 1.93) and 4.87
      (SD 1.96), respectively, and were not different for pregnant and non-pregnant
      patients. However, multivariate analyses showed that on average (anti-log
      transformed), each 1-h increase in the OPU-ICSI time reduced the likelihood of
      biochemical pregnancy by 7.3% (95% CI: 0.7-13.5%) and of clinical pregnancy by
      7.7% (95% CI 0.8-14.1%), after the fresh ET. No effect of time was observed for
      ongoing pregnancy or live birth rates. Increasing OPU-ICSI time increased the
      fertilization rate (B = 0.052, 95% CI: 0.022, 0.082). LIMITATIONS, REASONS FOR
      CAUTION: The lack of relationship between incubation time of oocytes and live
      birth rates might be due to uncontrolled variables. Given the population
      analyzed, these results should not be extended to other ART protocols such as in
      vitro maturation of oocytes or classical IVF fertilization. WIDER IMPLICATIONS OF
      THE FINDINGS: This study indicates that in vitro ageing of mature oocytes
      significantly affects the chances to become pregnant. Effect on live birth rates,
      although not evident in this study, cannot be excluded. Limiting incubation time
      of mature oocytes in the embryology laboratory should improve reproductive
      results for patients using their own oocytes and with a transfer of fresh
      embryos. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER:
      NA.

PMID- 29635448
TI  - Little genetic variability in resilience among cattle exists for a range of
      performance traits across herds in Ireland differing in Fasciola hepatica
      prevalence.
AB  - It is anticipated that in the future, livestock will be exposed to a greater risk
      of infection from parasitic diseases. Therefore, future breeding strategies for
      livestock, which are generally long-term strategies for change, should target
      animals adaptable to environments with a high parasitic load. Covariance
      components were estimated in the present study for a selection of dairy and beef
      performance traits over herd-years differing in Fasciola hepatica load using
      random regression sire models. Herd-year prevalence of F. hepatica was determined
      by using F. hepatica-damaged liver phenotypes which were recorded in abattoirs
      nationally. The data analyzed consisted up to 83,821 lactation records from dairy
      cows for a range of milk production and fertility traits, as well as 105,054
      young animals with carcass-related information obtained at slaughter. Reaction
      norms for individual sires were derived from the random regression coefficients.
      The heritability and additive genetic standard deviations for all traits analyzed
      remained relatively constant as herd-year F. hepatica prevalence gradient
      increased up to a prevalence level of 0.7; although there was a large increase in
      heritability and additive genetic standard deviation for milk and fertility
      traits in the observed F. hepatica prevalence levels >0.7, only 5% of the data
      existed in herd-year prevalence levels >0.7. Very little rescaling, therefore,
      exists across differing herd-year F. hepatica prevalence levels. Within-trait
      genetic correlations among the performance traits across different herd-year F.
      hepatica prevalence levels were less than unity for all traits. Nevertheless,
      within-trait genetic correlations for milk production and carcass traits were all
      >0.8 for F. hepatica prevalence levels between 0.2 and 0.8. The lowest estimate
      of within-trait genetic correlations for the different fertility traits ranged
      from -0.03 (SE = 1.09) in age of first calving to 0.54 (SE = 0.22) for calving to
      first service interval. Therefore, there was reranking of sires for fertility
      traits across different F. hepatica prevalence levels. In conclusion, there was
      little or no genetic variability in sensitivity to F. hepatica prevalence levels
      among cattle for milk production and carcass traits. But, some genetic
      variability in sensitivity among dairy cows did exist for fertility traits
      measured across herds differing in F. hepatica prevalence.

PMID- 29635451
TI  - Eribulin in BRAF V600E-mutant metastatic colorectal cancer: case series and
      potential rationale.

PMID- 29635452
TI  - Stability Study of Finasteride: Stability-Indicating LC Method, In Silico and LC
      ESI-MS Analysis of Major Degradation Product, and an In Vitro Biological Safety
      Study.
AB  - Stability studies of the pharmaceutically important compound finasteride were
      conducted in order to evaluate decomposition of the drug under forced degradation
      conditions. A simple stability-indicating liquid chromatography method was
      developed and validated for the evaluation of finasteride and degradation
      products formed in pharmaceutical preparations and the raw material. Isocratic LC
      separation was achieved on a C18 column using a mobile phase of o-phosphoric acid
      (0.1% v/v), adjusted to pH 2.8 with triethylamine (10% v/v) and acetonitrile
      (52:48 v/v), with a flow rate of 1.0 mL min-1. The alkaline degradation kinetics
      of the drug were also evaluated and could be best described as second-order
      kinetics under the experimental conditions applied for the tablets and raw
      material. Based on in silico studies and molecular weight confirmation, a
      comprehensive degradation pathway for the drug and the identity of its major
      product could be suggested without complicated isolation or purification
      processes. Furthermore, a biological safety study was performed to evaluate the
      effect of the degraded sample in relation to the intact molecule. The results
      showed that the degraded sample affected the cell proliferation. Therefore, these
      studies show that special care must be taken during the manipulation, manufacture
      and storage of this pharmaceutical drug.

PMID- 29635453
TI  - Circulating tumor DNA detection in hepatocellular carcinoma.

PMID- 29635454
TI  - Response to Dr. Kapural.

PMID- 29635456
TI  - Of mice and men: long-term safety of assisted reproduction treatments.

PMID- 29635455
TI  - Microbiome profiling of commercial pigs from farrow to finish.
AB  - Balanced bacterial communities within the gastrointestinal (GI) tract of animals
      are a key component of gut health, resulting in optimal performance and the
      prevention of disease. The purpose of this study was to characterize the
      commercial pig's baseline bacterial microbiome over time and across anatomical
      site. Several anatomical sites (duodenum/jejunum, ileum, cecum, and colon) were
      examined across multiple ages (days 0, 10, 21, 33, 62, 84, and market) for
      bacterial microbiome structure using 16S rRNA V4 region sequencing with Illumina
      MiSeq. General trends in the succession of the bacterial microbiome were observed
      over age, such as increasing populations of Clostridia and decreasing populations
      of Gammaproteobacteria (P < 0.05). However, apparent disruptions in the
      microbiome were also observed that did not follow these trends, specifically at
      sampling 24 h post-weaning where Lactobacillaceae were drastically reduced in
      relative abundance (P < 0.05). The introduction of solid feed between days 21 and
      33 had the greatest overall impact on bacterial community structure as compared
      with the effects of age, changes in solid feed type, and pig movement. A core
      bacterial microbiome was identified across all anatomical sites consisting of the
      dominant operational taxonomic units (OTUs); samples were only differentiated
      based upon anatomical site when considering less abundant OTUs and differences in
      relative abundance. When considering mucosal vs. digesta samples from the cecum
      and ileum, several taxa were of significantly higher relative abundance in the
      mucosa (P < 0.05), including Anaerovibrio, Bacteroides, Desulfovibrio,
      Helicobacter, Oscillospira, Phascolarctobacterium, and Prevotella. Correlations
      between several genus-level taxa and pig weight were observed. Overall, this
      study provides an expanded view of the dynamic pig GI microbiome from farrow to
      finish.

PMID- 29635457
TI  - Impact of Defaulting to Single-Lumen Peripherally Inserted Central Catheters on
      Patient Outcomes: An Interrupted Time Series Study.
AB  - Defaulting to single-lumen peripherally inserted central catheters (PICCs)
      ordered from non-critical care units resulted in a sustained reduction in PICC
      related complications. This system of care is transferrable to other
      institutions, with potential for improved patient safety and efficiency in
      outpatient parenteral antimicrobial therapy clinics.

PMID- 29635459
TI  - Corrigendum to "Reported Incidence and Survival of Fallopian Tube Carcinomas: A
      Population-Based Analysis From the North American Association of Central Cancer
      Registries".

PMID- 29635458
TI  - Selection in the Introgressed Regions of the Chimpanzee Genome.
AB  - During the demographic history of the Pan clade, there has been gene-flow between
      species, likely >200,000 years ago. Bonobo haplotypes in three subspecies of
      chimpanzee have been identified to be segregating in modern-day chimpanzee
      populations, suggesting that these haplotypes, with increased differentiation,
      may be a target of natural selection. Here, we investigate signatures of adaptive
      introgression within the bonobo-like haplotypes in chimpanzees using site
      frequency spectrum-based tests. We find evidence for subspecies-specific
      adaptations in introgressed regions involved with male reproduction in central
      chimpanzees, the immune system in eastern chimpanzees, female reproduction and
      the nervous system in Nigeria-Cameroon chimpanzees. Furthermore, our results
      indicate signatures of balancing selection in some of the putatively introgressed
      regions. This might be the product of long-term balancing selection resulting in
      a similar genomic signature as introgression, or possibly balancing selection
      acting on alleles reintroduced through gene flow.

PMID- 29635460
TI  - Breast Implant-Associated Bilateral B-Cell Lymphoma.
AB  - Lymphomas associated with implants are predominantly of T-cell type-with
      anaplastic large cell lymphoma (ALCL) being most reported. That said, to date 6
      cases of B-cell lymphoma associated with breast implants have been reported. All
      cases exhibited unilateral breast involvement. Here, the authors report a case of
      low-grade B-cell lymphoma occurring bilaterally in a 34-year-old woman with a
      history of Poly Implant Prosthese silicone implants at age 20, T-cell
      angioimmunoblastic lymphoma, and subsequent myeloablative double cord blood
      transplantation. Lymphoma cells were positive for CD20, CD5, BCL-2, CD21, CD23,
      IgD, IgM, with very low Ki-67 of 1%. Nevertheless, cases of ALCL associated with
      breast implants are rare but much more documented in literature than B-cell
      lymphomas associated with breast implants, as in this patient. Identification of
      a relationship between breast cancer and silicone is still ongoing in the
      literature, with long-term clinical follow-up required. More research will be
      necessary to fully characterize the occurrence, course, and association of this
      disease with breast implants in order to properly guide diagnosis and management.

PMID- 29635461
TI  - Doctor-couple communication during assisted reproductive technology visits.
AB  - STUDY QUESTION: What are the characteristics of doctor-couple communication
      content during actual ART visits? SUMMARY ANSWER: Physicians were mainly focused
      on providing biomedical information, while communication content from couples had
      a 2-fold focus on providing biomedical information and on positive talk. WHAT IS
      KNOWN ALREADY: Communication aspects in ART seem crucial for clinical decision
      making, retention in care and critical conversations with couples due to low
      treatment success rates. However, no studies have been carried out on the actual
      interaction between the doctor and the couple in this context. STUDY DESIGN,
      SIZE, DURATION: This observational study involved 28 clinicians and 160 patients
      referred to eight Italian ART clinics during a one-year recruitment period.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: ART visits at eight Italian clinics
      were videotaped. The visits were coded using the Roter Interaction Analysis
      System (RIAS), particularly focusing on RIAS composite categories, verbal
      dominance and patient-centeredness score. MAIN RESULTS AND THE ROLE OF CHANCE: A
      total of 85 visits were eligible for analysis (62% acceptance rate), involving 28
      clinicians and 160 patients (including 75 couples). The average visit duration
      was 37 +/- 17.7 min. The mean verbal dominance was 1.9 +/- 0.86 (range: 0.72
      5.74). Physicians mainly focused on providing biomedical information.
      Communication content from couples had a 2-fold focus on providing biomedical
      information and on positive talk. The mean of patient centeredness index (PCI)
      was 0.51 (SD = 0.28; range 0.08-1.77); visits in which the doctor was a woman or
      the treatment indication was for heterologous fertilization showed higher PCI
      scores. Overall, females accounted for 67% of all patient talk. Taking this
      imbalance into account as expected frequencies for each composite category, males
      reported significantly more utterances in almost all of the socioemotional
      categories. LIMITATIONS, REASONS FOR CAUTION: These results are preliminary and
      observational and only regard Italy. Communication during visits may have been
      biased since the professionals who agreed to participate showed an interest in
      communication issues. Another limitation is a possible Hawthorne effect due to
      the fact that participants were aware of being videotaped. WIDER IMPLICATIONS OF
      THE FINDINGS: Our study showed that ART physicians mainly adopted an informative
      model of communication and a more disease-oriented approach. Findings revealed
      the complexity of communication content during ART consultations, given its
      triadic characteristic in which the third party is also a patient; clinicians
      should be aware of this complex aspect and of the specific male and female
      perspectives to be taken into account. The results could be useful for training
      ART professionals. STUDY FUNDING/COMPETING INTEREST(S): This study was possible
      thanks to an unconditional grant from Ferring Spa to the Department of Health
      Sciences, University of Milan. There are no competing interests to declare. TRIAL
      REGISTRATION NUMBER: N/A.

PMID- 29635462
TI  - Low prevalence of transmitted HIV-1 drug resistance detected by a dried blood
      spot (DBS)-based next-generation sequencing (NGS) method in newly diagnosed
      individuals in Cameroon in the years 2015-16.
AB  - Objectives: To determine the most recent prevalence, transmission patterns and
      risk factors of transmitted drug-resistance mutations (TDRMs) in Cameroon, we
      initiated a multicentre study monitoring HIV-1 drug resistance in newly HIV-1
      diagnosed individuals using a novel next-generation sequencing (NGS) assay
      applicable to fingerprick dried blood spot (DBS) samples. Methods: Fingerprick
      DBS samples and questionnaires were collected from 360 newly HIV-1-diagnosed
      individuals in four hospitals in urban areas in Cameroon in the years 2015-16. We
      developed an HIV-1 protease and reverse transcriptase drug resistance genotyping
      assay applicable to DBS samples and HIV-1 genomes of groups M, N and O. The WHO
      2009 list of mutations for surveillance of transmitted drug-resistant HIV strains
      was used to analyse TDRMs. Results: Applying our 'DBS-NGS-genotypic resistance
      test', baseline HIV-1 drug resistance data were successfully obtained from 82.8%
      (298/360) of newly diagnosed individuals. At nucleotide frequencies >15%, TDRMs
      to NRTIs were observed in 3.0% (9/298), to NNRTIs in 4.0% (12/298) and to PIs in
      1.3% (3/240). The NNRTI mutation K103N was most commonly detected (2.7%).
      Expanding the analysis to low-abundance TDRMs, i.e. 3%-15%, 12 additional
      individuals (4.0%) harbouring TDRMs were identified. Having unprotected sex with
      a known HIV-1-positive person was significantly associated with the transmission
      of DRMs (adjusted OR 9.6; 95% CI 1.79-51.3). Conclusions: The prevalence of
      transmitted HIV-1 drug resistance is currently low in the study sites in
      Cameroon. Evidence of some risky sexual behaviours depicts a public health
      problem with possible implications for the prevention of new HIV-1 infections.

PMID- 29635463
TI  - Lexical and Grammatical Factors in Sentence Production in Semantic Dementia:
      Insights From Greek.
AB  - Purpose: Language production in semantic dementia (SD) is characterized by a
      lexical-semantic deficit and largely preserved argument structure and inflection
      production. This study investigates (a) the effect of argument structure on verb
      retrieval and (b) the interrelation between inflection marking and verb retrieval
      in SD. Method: Seven individuals with SD and 7 healthy controls performed 2
      sentence elicitation tasks. In Experiment 1, participants described the action
      taking place in a video. In Experiment 2, they watched the same videos preceded
      by a phrase prompting the production of past tense. Three verb classes were
      tested: (a) unergative (e.g., to walk), (b) unaccusative (e.g., to fall), and (c)
      transitive with 1 object (e.g., to read a book). Results: There was not any
      quantitative difference among the verb classes in Experiment 1, but error
      analysis hinted at difficulties related with argument structure complexity. The
      findings of Experiment 2 suggest no general effect of inflection on verb
      retrieval; nevertheless, inflection marking impeded the retrieval of verbs with
      complex argument structure. Large individual variation was established.
      Conclusions: Argument structure complexity may challenge speakers with SD. Verb
      retrieval and inflection marking seem to interrelate at the expense of the
      former. Inflection production may be affected at severe stages of the disease.
      Supplemental Material: https://doi.org/10.23641/asha.6030779.

PMID- 29635464
TI  - Alcohol and gender gaps in life expectancy in eight Central and Eastern European
      countries.
AB  - Background: Gender differences in life expectancy (LE) have been traditionally
      large in Central and Eastern Europe (CEE), and alcohol has been hypothesized to
      be one of its main determinants. We examined the role of alcohol in gender
      differences in LE in Estonia, Lithuania, Latvia, Moldova, Poland, Romania, Russia
      and Ukraine, and changes in this role from 1965 until 2012. Methods: We
      decomposed the gender differences in LE at birth into alcohol- and non-alcohol
      related mortality. We examined causes of death wholly attributable to alcohol
      over the whole period, and estimated from 1990 onwards additional alcohol
      attributable mortality by using alcohol-attributable fractions from the Global
      Burden of Disease study. Results: In the eight CEE countries, women's advantage
      in LE relative to men increased from 7.3 years on average in 1965 to 10.0 years
      on average in 2012. All alcohol-attributable mortality contributed 1.9 years on
      average (uncertainty intervals (UI): 1.2-2.5; 18.8%) to the gender differences
      from 1990 to 2012. Its relative contribution increased in most countries until
      around 2005, and declined thereafter, resulting in a contribution of at least 15%
      in 2012. The absolute contribution of alcohol to the LE gender gap was strongly
      correlated with the overall LE gender differences (Pearson's r > 0.75), except in
      Poland and Estonia. Conclusions: Despite recent declines, the contribution of sex
      differences in excessive alcohol consumption to the LE gender gap is substantial,
      and should not be neglected. Tackling gender differences in alcohol consumption
      and alcohol-attributable mortality would contribute to further progress in
      reducing mortality.

PMID- 29635467
TI  - Role of medical ozone in attenuating age-related changes in the rat cerebellum.
AB  - Aging is an inevitable biological process characterized by motor in coordination
      and decline in the ability to learn new motor skills. The purpose of this study
      is to investigate, for the first time, the beneficial antiaging effects of
      medical ozone (O3) on the age-related structural damage of the rat cerebellum. We
      have examined the cerebellum of albino rats at the ages of 6, 20 and 22, and the
      effect of intraperitoneal medical O3 administration (0.7 g/kg) by histological,
      immunohistochemical and morphometric studies. Age-related changes in the
      cerebellum were in the form of a significant reduction in the number of Purkinje
      cells (PCs), which appeared shrunken with a darkly stained cytoplasm and
      vacuolated spaces in all layers. The decrease in Nissl granule content of the PCs
      was also observed. A significant reduction in Mab2, Ki67 immunoreactivity
      associated with significant increase in glial fibrillary acidic protein, Caspase
      3 and iNos immunoreactivity were also detected. Medical O3 administration
      reversed all these histopathological and immunohistochemical changes. This
      protective effect was mediated by reducing oxidative stress, apoptosis, astrocyte
      activation and improving both neuritogenesis and neurogenesis. We can conclude
      from the results of the present study that medical O3 can prevent the retardation
      of age-related changes in rat cerebellum.

PMID- 29635465
TI  - Risk of Progressive Multifocal Leukoencephalopathy in the Combination
      Antiretroviral Therapy Era in the French Hospital Database on Human
      Immunodeficiency Virus (ANRS-C4).
AB  - Background: Risk factors for progressive multifocal leukoencephalopathy (PML) in
      individuals with human immunodeficiency virus (HIV) infection are poorly
      documented in the era of combination antiretroviral therapy (cART). Methods: We
      studied HIV-1-infected individuals aged >=15 years who had no history of PML and
      were prospectively followed up between 1997 and 2011 in the French Hospital
      Database on HIV (FHDH-ANRS CO4) cohort. Cox models were used to calculate
      adjusted hazard ratios (HRs), focusing on sub-Saharan origin, suggested to be
      protective, and recent cART initiation, potentially associated with an increased
      risk of PML. Results: PML developed in 555 individuals, in 57 during the first 6
      months of cART. From 1997-2000 to 2009-2011, the incidence fell from 1.15 (95%
      confidence interval [CI], .98-1.31) to 0.49 (.37-.61) per 1000 person-years. Sub
      Saharan African origin had no clear influence (HR, 0.80; 95% CI, .58-1.11).
      Compared with men who have sex with men, injection drug users (IDUs) were at
      higher risk (HR, 1.80 [95% CI, 1.32-2.45] for male and 1.68 [1.13-2.48] for
      female IDUs). When IDUs were excluded, hepatitis C virus seropositivity was
      associated with an increased risk (HR, 1.40; 95% CI, 1.02-1.93). Compared with no
      cART initiation, initiation <6 months previously was associated with PML onset
      (HR, 4.91; 95% CI, 2.42-9.95). Conclusions: Recent cART initiation is associated
      with an increased risk of PML, as are injection drug use and hepatitis C virus
      seropositivity. Sub-Saharan African origin had no protective effect.

PMID- 29635466
TI  - Application of a Multistate Model to Evaluate Visit Burden and Patient Stability
      to Improve Sustainability of Human Immunodeficiency Virus Treatment in Zambia.
AB  - Background: Differentiated service delivery (DSD) for human immunodeficiency
      virus (HIV)-infected persons who are clinically stable on antiretroviral therapy
      (ART) has been embraced as a solution to decrease access barriers and improve
      quality of care. However, successful DSD implementation is dependent on
      understanding the prevalence, incidence, and durability of clinical stability.
      Methods: We evaluated visit data in a cohort of HIV-infected adults who made at
      least 1 visit between 1 March 2013 and 28 February 2015 at 56 clinics in Zambia.
      We described visit frequency and appointment intervals using conventional
      stability criteria and used a mixed-effects linear regression model to identify
      predictors of appointment interval. We developed a multistate model to
      characterize patient stability over time and calculated incidence rates for
      transition between states. Results: Overall, 167819 patients made 3418018 post
      ART initiation visits between 2004 and 2015. Fifty-four percent of visits were
      pharmacy refill-only visits, and 24% occurred among patients on ART for >6 months
      and whose current CD4 was >500 cells/mm3. Median appointment interval at
      clinician visits was 59 days, and time on ART and current CD4 were not strong
      predictors of appointment interval. Cumulative incidence of clinical stability
      was 66.2% at 2 years after enrollment, but transition to instability (31 events
      per 100 person-years) and lapses in care (41 events per100 person-years) were
      common. Conclusions: Current facility-based care was characterized by high visit
      burden due to pharmacy refills and among treatment-experienced patients.
      Differentiated service delivery models targeted toward stable patients need to be
      adaptive given that clinical stability was highly transient and lapses in care
      were common.

PMID- 29635468
TI  - Antibiotic resistance phenotypes and virulence-associated genes in Escherichia
      coli isolated from animals and animal food products in Tunisia.
AB  - Livestock and food products of animal origin constitute important reservoirs of
      intestinal and extraintestinal pathogenic Escherichia coli including antibiotic
      resistant E. coli isolates. To assess potential risks to public health related to
      E. coli strains of animal origin in Tunisia, 65 E. coli isolates recovered from
      healthy animals and food products of animal origin were studied. Antimicrobial
      susceptibility was determined according to CLSI guidelines and genes encoding
      antibiotic resistance as well as virulence factors were investigated by PCR. High
      rates of antibiotic resistance were observed to kanamycin (78.4%), gentamicin
      (75.3%) and streptomycin (75.3%, encoded by strA-strB (7 isolates)), amoxicillin
      (64.6%), amoxicillin/clavulanic acid (60%), tetracycline (44.6%; tetA (8
      isolates) and tetB (7 isolates)), nalidixic acid (27.6%, qnrS (3 isolates), qnrB
      (2 isolates) and qnrA (one isolate)) and sulfonamides (36.9%; sul1 (1 isolate),
      sul2 (4 isolates), and sul3 (1 isolate)). Virulotypes classified some isolates as
      STEC (3%), MNEC (1.5%) and atypical EPEC (1.5%). This study demonstrated high
      rates of antimicrobial resistance and the presence of some pathogenic pathovars
      from animal origins that are a cause of concern for public health.

PMID- 29635469
TI  - Toward a normalized clinical drug knowledge base in China-applying the RxNorm
      model to Chinese clinical drugs.
AB  - Objective: In recent years, electronic health record systems have been widely
      implemented in China, making clinical data available electronically. However,
      little effort has been devoted to making drug information exchangeable among
      these systems. This study aimed to build a Normalized Chinese Clinical Drug
      (NCCD) knowledge base, by applying and extending the information model of RxNorm
      to Chinese clinical drugs. Methods: Chinese drugs were collected from 4 major
      resources-China Food and Drug Administration, China Health Insurance Systems,
      Hospital Pharmacy Systems, and China Pharmacopoeia-for integration and
      normalization in NCCD. Chemical drugs were normalized using the information model
      in RxNorm without much change. Chinese patent drugs (i.e., Chinese herbal
      extracts), however, were represented using an expanded RxNorm model to
      incorporate the unique characteristics of these drugs. A hybrid approach
      combining automated natural language processing technologies and manual review by
      domain experts was then applied to drug attribute extraction, normalization, and
      further generation of drug names at different specification levels. Lastly, we
      reported the statistics of NCCD, as well as the evaluation results using several
      sets of randomly selected Chinese drugs. Results: The current version of NCCD
      contains 16 976 chemical drugs and 2663 Chinese patent medicines, resulting in 19
      639 clinical drugs, 250 267 unique concepts, and 2 602 760 relations. By manual
      review of 1700 chemical drugs and 250 Chinese patent drugs randomly selected from
      NCCD (about 10%), we showed that the hybrid approach could achieve an accuracy of
      98.60% for drug name extraction and normalization. Using a collection of 500
      chemical drugs and 500 Chinese patent drugs from other resources, we showed that
      NCCD achieved coverages of 97.0% and 90.0% for chemical drugs and Chinese patent
      drugs, respectively. Conclusion: Evaluation results demonstrated the potential to
      improve interoperability across various electronic drug systems in China.

PMID- 29635470
TI  - In pursuit of quality and safety: an 8-year study of clinical peer review best
      practices in US hospitals.
AB  - Objectives: Gather normative data on the goals of clinical peer review; refine a
      best-practice model and related self-assessment inventory; identify the interval
      progress towards best-practice adoption. Design: Online survey (2015-16) of a
      cohort of 457 programs first studied by volunteer sampling in either 2007 or 2009
      on 40 items assessing the degree of conformance to a validated quality
      improvement (QI) model and addressing program goals, structure, process,
      governance, and impact on quality and safety. Setting: Acute care hospitals of
      all sizes in the USA. Study Participants: Physicians and hospital leaders or
      hospital staff with intimate program knowledge. Intervention: None. Main Outcome
      Measures: Subjectively-rated program impact on quality and safety; QI model
      score. Results: Two hundred and seventy responses (59% response rate) showed that
      clinical peer review most commonly aims to improve quality and safety. From 2007
      to 2015, the median [inter-quartile range, IQR] annual rate of major program
      change was 20% [11-24%]. Mean [confidence interval, CI] QI model scores increased
      5.6 [2.9-8.3] points from 46.2 at study entry. Only 35% scored at least 60 of 80
      possible points-'C' level progress in adopting the QI model. The analysis
      supports expansion of the QI model and an associated self-assessment inventory to
      include 20 items on a 100-point scale for which a 10-point increase predicts a
      one level improvement in quality impact with an odds ratio [CI] of 2.5 [2.2-3.0].
      Conclusions: Hospital and physician leaders could potentially accelerate progress
      in quality and safety by revisiting their clinical peer review practices in light
      of the evidence-based QI model.

PMID- 29635471
TI  - Impact of mass drug administration campaigns depends on interaction with seasonal
      human movement.
AB  - Background: Mass drug administration (MDA) is a control and elimination tool for
      treating infectious diseases. For malaria, it is widely accepted that conducting
      MDA during the dry season results in the best outcomes. However, seasonal
      movement of populations into and out of MDA target areas is common in many places
      and could potentially fundamentally limit the ability of MDA campaigns to achieve
      elimination. Methods: A mathematical model was used to simulate malaria
      transmission in two villages connected to a high-risk area into and out of which
      10% of villagers traveled seasonally. MDA was given only in the villages.
      Prevalence reduction under various possible timings of MDA and seasonal travel
      was predicted. Results: MDA is most successful when distributed outside the
      traveling season and during the village low-transmission season. MDA is least
      successful when distributed during the traveling season and when traveling
      overlaps with the peak transmission season in the high-risk area. Mistiming MDA
      relative to seasonal travel resulted in much poorer outcomes than mistiming MDA
      relative to the peak transmission season within the villages. Conclusions:
      Seasonal movement patterns of high-risk groups should be taken into consideration
      when selecting the optimum timing of MDA campaigns.

PMID- 29635472
TI  - Limitations of ceftriaxone compared with cefazolin against MSSA: an integrated
      pharmacodynamic analysis.
AB  - Objectives: Despite the convenience of once-daily dosing, the use of ceftriaxone
      for Staphylococcus aureus infections has significant limitations, including
      scarce clinical evidence and increasingly questionable pharmacodynamic activity.
      Our goal was to conduct an integrated pharmacokinetic-pharmacodynamic analysis of
      the appropriateness of ceftriaxone compared with cefazolin for treating serious
      MSSA infections. Methods: Ceftriaxone and cefazolin activity against five
      clinical MSSA isolates was characterized in an in vitro pharmacodynamic model.
      Monte Carlo simulations were then used to evaluate various dosing regimens of
      ceftriaxone and cefazolin based on relevant patient pharmacokinetic data,
      significant pharmacodynamic targets derived from the in vitro studies (55%fT>MIC
      for bacteriostasis, 75%fT>MIC for 1 log10 bacterial kill, 100%fT>MIC for >=3
      log10 bacterial kill) and MIC distributions for MSSA from national surveillance
      data. Results: Ceftriaxone at 1 g once daily had poor activity against MSSA with
      net bacterial growth predicted in 76% of simulated subjects. The standard 2 g of
      ceftriaxone once daily had predicted bacterial growth or bacteriostasis in 54% of
      cases with bactericidal effects in only 17%. Cefazolin at 2 g once daily was
      notably similar to ceftriaxone in expected target attainments. Cefazolin at 2 g
      twice daily demonstrated maximal pharmacodynamic activity with bactericidal
      effects in 97% of simulated subjects. Conclusions: Given the limited activity of
      ceftriaxone against S. aureus, particularly for serious infections when bacterial
      kill is desired, the convenience of once-daily dosing should be weighed against
      the risks of using an overly broad, suboptimal therapy. Cefazolin warrants
      further consideration, particularly as optimal pharmacodynamics against MSSA may
      be achieved with twice-daily dosing in most patients.

PMID- 29635473
TI  - Type 1 diabetes mellitus and risk of cancer: a meta-analysis of observational
      studies.
AB  - Objective: Previous observational studies have focused on the link between type 2
      diabetes and the risk of cancer. However, the association between type 1 diabetes
      and the risk of cancer has not been well addressed. This study aimed to
      investigate the association between type 1 diabetes and the risk of cancer by
      using a meta-analysis of observational studies. Methods: We searched PubMed and
      EMBASE for observational studies that examined the association between type 1
      diabetes and cancer in April 2017. We calculated the pooled odds ratios (ORs) or
      relative risks (RRs) with confidence intervals (CIs) from individual studies
      based on a random-effects model meta-analysis. Results: We included a total of 15
      observational studies with two case-control studies and 13 cohort studies
      involving 31 893 cancer patients among a total of 1 915 179 participants in the
      final analysis. In the random-effects meta-analysis of all studies, patients with
      type 1 diabetes had an increased risk of cancer (OR or RR, 1.29; 95% CI, 1.09
      1.52; n = 15; I2 = 95.2%). In the subgroup meta-analysis by type of cancer, type
      1 diabetes significantly increased the risk of cancers of stomach, lung,
      pancreas, liver, ovary and kidney, whereas it significantly decreased the risk of
      breast cancer (OR or RR, 0.91; 95% CI, 0.86-0.95; n = 9; I2 = 0%). Conclusion:
      This meta-analysis suggests that type 1 diabetes is associated with the increased
      risk of several types of cancer and the decreased risk of breast cancer. However,
      the plausible mechanisms for the decreased risk of breast cancer remain unclear.
      Further prospective studies with proper adjustment for possible confounding
      factors are warranted.

PMID- 29635474
TI  - Crystal structure and mutational analysis of Mycobacterium smegmatis FenA
      highlight active site amino acids and three metal ions essential for flap
      endonuclease and 5' exonuclease activities.
AB  - Mycobacterium smegmatis FenA is a nucleic acid phosphodiesterase with flap
      endonuclease and 5' exonuclease activities. The 1.8 A crystal structure of FenA
      reported here highlights as its closest homologs bacterial FEN-family enzymes
      ExoIX, the Pol1 exonuclease domain and phage T5 Fen. Mycobacterial FenA
      assimilates three active site manganese ions (M1, M2, M3) that are coordinated,
      directly and via waters, to a constellation of eight carboxylate side chains. We
      find via mutagenesis that the carboxylate contacts to all three manganese ions
      are essential for FenA's activities. Structures of nuclease-dead FenA mutants
      D125N, D148N and D208N reveal how they fail to bind one of the three active site
      Mn2+ ions, in a distinctive fashion for each Asn change. The structure of FenA
      D208N with a phosphate anion engaged by M1 and M2 in a state mimetic of a product
      complex suggests a mechanism for metal-catalyzed phosphodiester hydrolysis
      similar to that proposed for human Exo1. A distinctive feature of FenA is that it
      does not have the helical arch module found in many other FEN/FEN-like enzymes.
      Instead, this segment of FenA adopts a unique structure comprising a short 310
      helix and surface beta-loop that coordinates a fourth manganese ion (M4).

PMID- 29635475
TI  - Socioeconomic multi-domain health inequalities in Dutch primary school children.
AB  - Background: This study assesses socio-economic health inequalities (SEHI) over
      primary school-age (4- to 12-years old) across 13 outcomes (i.e. body-mass index
      [BMI], handgrip strength, cardiovascular fitness, current physical conditions,
      moderate to vigorous physical activity, sleep duration, daily fruit and vegetable
      consumption, daily breakfast, exposure to smoking, mental strengths and
      difficulties, self-efficacy, school absenteeism and learning disabilities),
      covering four health domains (i.e. physical health, health behaviour, mental
      health and academic health). Methods: Multilevel mixed effect (linear and
      logistic) regression analyses were applied to cross-sectional data of a Dutch
      quasi-experimental study that included 1403 pupils from nine primary schools.
      Socioeconomic background (high-middle-low) was indicated by maternal education (n
      = 976) and parental material deprivation (n = 784). Results: Pupils with higher
      educated mothers had lower BMIs, higher handgrip strength and higher
      cardiovascular fitness; their parents reported more daily fruit and vegetable
      consumption, daily breakfast and less exposure to smoking. Furthermore these
      pupils showed less mental difficulties and less school absenteeism compared with
      pupils whose mothers had a lower education level. When using parental material
      deprivation as socio-economic indicator, similar results were found for BMI,
      cardiovascular fitness, sleep duration, exposure to smoking and mental strengths
      and difficulties. Socio-economic differences in handgrip strength, cardiovascular
      fitness and sleep duration were larger in older than in younger pupils.
      Conclusions: Childhood SEHI are clearly found across multiple domains, and some
      are larger in older than in younger pupils. Interventions aiming to tackle SEHI
      may therefore need a comprehensive and perhaps more fundamental approach.

PMID- 29635476
TI  - Targeting IS608 transposon integration to highly specific sequences by structure
      based transposon engineering.
AB  - Transposable elements are efficient DNA carriers and thus important tools for
      transgenesis and insertional mutagenesis. However, their poor target sequence
      specificity constitutes an important limitation for site-directed applications.
      The insertion sequence IS608 from Helicobacter pylori recognizes a specific
      tetranucleotide sequence by base pairing, and its target choice can be re
      programmed by changes in the transposon DNA. Here, we present the crystal
      structure of the IS608 target capture complex in an active conformation,
      providing a complete picture of the molecular interactions between transposon and
      target DNA prior to integration. Based on this, we engineered IS608 variants to
      direct their integration specifically to various 12/17-nt long target sites by
      extending the base pair interaction network between the transposon and the target
      DNA. We demonstrate in vitro that the engineered transposons efficiently select
      their intended target sites. Our data further elucidate how the distinct
      secondary structure of the single-stranded transposon intermediate prevents
      extended target specificity in the wild-type transposon, allowing it to move
      between diverse genomic sites. Our strategy enables efficient targeting of unique
      DNA sequences with high specificity in an easily programmable manner, opening
      possibilities for the use of the IS608 system for site-specific gene insertions.

PMID- 29635477
TI  - Pharmacogenomics and big genomic data: from lab to clinic and back again.
AB  - The field of pharmacogenomics is an area of great potential for near-term human
      health impacts from the big genomic data revolution. Pharmacogenomics research
      momentum is building with numerous hypotheses currently being investigated
      through the integration of molecular profiles of different cell lines and large
      genomic data sets containing information on cellular and human responses to
      therapies. Additionally, the results of previous pharmacogenetic research efforts
      have been formulated into clinical guidelines that are beginning to impact how
      healthcare is conducted on the level of the individual patient. This trend will
      only continue with the recent release of new datasets containing linked genotype
      and electronic medical record data. This review discusses key resources available
      for pharmacogenomics and pharmacogenetics research and highlights recent work
      within the field.

PMID- 29635478
TI  - Nightly Biting Cycles of Anopheles Species in Rural Northwestern Burkina Faso.
AB  - The biting behavior of anophelines is an important determinant of malaria
      transmission. Understanding the local vector host-seeking behavior, its outdoor/
      indoor biting preference, and nocturnal biting periods is essential for
      effectively applying and improving vector control methods, such as Long Lasting
      Insecticidal Nets (LLINs) and personal protective measures. To better understand
      the biting and host-seeking patterns of Anopheles mosquitoes in Northwestern
      Burkina Faso, we performed biweekly Human Landing Catches (HLC) in six villages
      during the period of highest mosquito abundance and malaria transmission. We
      applied a negative binomial regression framework to statistically analyze the
      host-seeking activities of Anopheles species and test for differences across
      hours, months, and villages, as well as for differences between indoor and
      outdoor capture points. Anopheles gambiae s.l. was identified as the main malaria
      vector in this region, representing about 90% of the total anopheline population.
      Biting activity was significantly different across hours and showed a peaked
      plateau between 2000 and 0200 hours. Differences in the pattern of biting cycles
      were observed between the early and late rainy season. This study shows that
      anopheline biting activity in Northwest Burkina Faso is high throughout the
      night, at indoor and outdoor posts alike. Consequently, bed nets alone may not
      provide sufficient protection against early biting anophelines and should be
      complemented with additional strategies such as indoor residual spraying (IRS)
      and larval source management (LSM) to meet the WHO's ambitious goals that are
      reflected in the global technical malaria strategy for 2030.

PMID- 29635480
TI  - Two J domains ensure high cochaperone activity of DnaJ, Escherichia coli heat
      shock protein 40.
AB  - Heat shock protein 70 (Hsp70) chaperone systems consist of Hsp70, Hsp40 and a
      nucleotide-exchange factor and function to help unfolded proteins achieve their
      native conformations. Typical Hsp40s assume a homodimeric structure and have both
      chaperone and cochaperone activity. The dimeric structure is critical for
      chaperone function, whereas the relationship between the dimeric structure and
      cochaperone function is hardly known. Here, we examined whether two intact
      protomers are required for cochaperone activity of Hsp40 using an Escherichia
      coli Hsp70 chaperone system consisting of DnaK, DnaJ and GrpE. The expression
      systems were generated and two heterodimeric DnaJs that included a mutated
      protomer lacking cochaperone activity were purified. Normal chaperone activity
      was demonstrated by assessing aggregation prevention activity using urea
      denatured luciferase. The heterodimeric DnaJs were investigated for cochaperone
      activity by measuring DnaK ATPase activity and the heat-denatured glucose-6
      phosphate dehydrogenase refolding activity of the DnaK chaperone system, and they
      showed reduced cochaperone activity. These results indicate that two intact
      protomers are required for high cochaperone activity of DnaJ, suggesting that one
      homodimeric DnaJ molecule promotes the simultaneous binding of multiple DnaK
      molecules to one substrate molecule, and that this binding mode is required for
      the efficient folding of denatured proteins.

PMID- 29635479
TI  - A practical blueprint to systematically study life-long health consequences of
      novel medically assisted reproductive treatments.
AB  - In medicine, safety and efficacy are the two pillars on which the implementation
      of novel treatments rest. To protect the patient from unnecessary or unsafe
      treatments, usually, a stringent path of (pre) clinical testing is followed
      before a treatment is introduced into routine patient care. However, in
      reproductive medicine several techniques have been clinically introduced without
      elaborate preclinical studies. Moreover, novel reproductive techniques may harbor
      safety risks not only for the patients undergoing treatment, but also for the
      offspring conceived through these techniques. If preclinical (animal) studies
      were performed, efficacy and functionality the upper hand. When a new medically
      assisted reproduction (MAR) treatment was proven effective (i.e. if it resulted
      in live birth) the treatment was often rapidly implemented in the clinic. For
      IVF, the first study on the long-term health of IVF children was published a
      decade after its clinical implementation. In more recent years, prospective
      follow-up studies have been conducted that provided the opportunity to study the
      health of large groups of children derived from different reproductive
      techniques. Although such studies have indicated differences between children
      conceived through MAR and children conceived naturally, results are often
      difficult to interpret due to the observational nature of these studies (and the
      associated risk of confounding factors, e.g. subfertility of the parents),
      differences in definitions of clinical outcome measures, lack of uniformity in
      assessment protocols and heterogeneity of the underlying reasons for fertility
      treatment. With more novel MARs waiting at the horizon, there is a need for a
      framework on how to assess safety of novel reproductive techniques in a
      preclinical (animal) setting before they are clinically implemented. In this
      article, we provide a blueprint for preclinical testing of safety and health of
      offspring generated by novel MARs using a mouse model involving an array of tests
      that comprise the entire lifespan. We urge scientists to perform the proposed
      extensive preclinical tests for novel reproductive techniques with the goal to
      acquire knowledge on efficacy and the possible health effects of to-be
      implemented reproductive techniques to safeguard quality of novel MARs.

PMID- 29635481
TI  - B chromosomes are associated with redistribution of genetic recombination towards
      lower recombination chromosomal regions in perennial ryegrass.
AB  - Supernumerary 'B' chromosomes are non-essential components of the genome present
      in a range of plant and animal species-including many grasses. Within diploid and
      polyploid ryegrass and fescue species, including the forage grass perennial
      ryegrass (Lolium perenne L.), the presence of B chromosomes has been reported as
      influencing both chromosome pairing and chiasma frequencies. In this study, the
      effects of the presence/absence of B chromosomes on genetic recombination has
      been investigated through generating DArT (Diversity Arrays Technology) marker
      genetic maps for six perennial ryegrass diploid populations, the pollen parents
      of which contained either two B or zero B chromosomes. Through genetic and
      cytological analyses of these progeny and their parents, we have identified that,
      while overall cytological estimates of chiasma frequencies were significantly
      lower in pollen mother cells with two B chromosomes as compared with zero B
      chromosomes, the recombination frequencies within some marker intervals were
      actually increased, particularly for marker intervals in lower recombination
      regions of chromosomes, namely pericentromeric regions. Thus, in perennial
      ryegrass, the presence of two B chromosomes redistributed patterns of meiotic
      recombination in pollen mother cells in ways which could increase the range of
      allelic variation available to plant breeders.

PMID- 29635482
TI  - MADS transcription factors cooperate: complexities of complex formation.

PMID- 29635483
TI  - Reflections from the Janus face of gibberellin in legume nodulation.

PMID- 29635484
TI  - A Comparative Assessment of the Response of Two Species of Cucumber Beetles
      (Coleoptera: Chrysomelidae) to Visual and Olfactory Cues and Prospects for Mass
      Trapping.
AB  - Spotted (Diabrotica undecimpunctata howardii) and striped (Acalymma vittatum)
      cucumber beetles (Coleoptera: Chrysomelidae) are serious pests of field-grown
      cucurbits in most areas of the United States where these crops are grown. This
      study aimed at quantifying, using a comparative approach, the behavioral response
      of A. vittatum and D. u. howardii to visual and olfactory cues associated with
      different trap types. In a first field study, Pherocon corn rootworm (CRW) traps
      baited with a 5-component floral-based lure (= AgBio lure) captured significantly
      more A. vittatum than traps baited with any other commercial lure. When used in
      combination with yellow sticky cards, the AgBio lure outperformed the other lures
      except for the Trece lure TRE8274. Subsequent tests revealed that the response of
      both cucumber beetle species to the AgBio lure was positively associated with
      increases in the amount of lure used. In the last series of tests that involved
      color discrimination by the beetles, traps constructed using 3.8-liter jugs
      painted yellow outperformed the CRW trap. Results from on-farm research,
      conducted at a commercial vegetable farm, confirmed the beetles' visual
      preference for yellow, and also revealed an excellent performance of the mass
      trapping system, which kept cucumber beetle densities in the cash crop below
      economic thresholds. Combined findings indicate that the mass trapping system
      developed can be implemented as part of a broader IPM program aimed at managing
      cucumber beetles.

PMID- 29635486
TI  - Erratum for Langeveld et al. No metabolic effects of mustard allyl-isothiocyanate
      compared with placebo in men. Am J Clin Nutr 2017;106:1197-205.

PMID- 29635487
TI  - The effect of dietary glycemic index and glycemic load on inflammatory
      biomarkers: a systematic review and meta-analysis of randomized clinical trials.
AB  - Background: To our knowledge, there is no study available that summarizes earlier
      findings on the effect of dietary glycemic index (GI) and glycemic load (GL) on
      inflammatory biomarkers. Objective: This systematic review and meta-analysis was
      conducted to systematically review the available clinical trials that examined
      the effects of low-GI (LGI) and low-GL (LGL) diets on several inflammatory
      biomarkers in adults. Design: We searched for relevant articles published up to
      June 2017 through PubMed, Medline, SCOPUS, EMBASE, and Google Scholar with the
      use of relevant keywords. Clinical trials that examined the effect of dietary GI
      and GL on inflammation in adults were included. Results: Overall, 28 randomized
      controlled trials (RCTs) including 2961 participants (59% women, 41% men) were
      included in this meta-analysis. By combining findings from 14 studies on high
      sensitivity C-reactive protein (hs-CRP) concentrations, we found no significant
      effect of LGI or LGL diets on serum hs-CRP concentrations compared with the
      control diet [weighted mean difference (WMD) for dietary GI: -0.05 mg/L (95% CI: 
      0.21, 0.10 mg/L); and WMD for dietary GL: 0.08 mg/L (95% CI: -0.26, 0.42 mg/L),
      respectively]. After combining effect sizes from 5 studies, we did not find
      significant changes in serum tumor necrosis factor alpha (TNF-alpha)
      concentrations comparing control diets with LGI (WMD: -0.18 mg/L; 95% CI: -0.43,
      0.06 mg/L) or LGL (WMD: -0.20 mg/L; 95% CI: -0.33, 0.07 mg/L) diets. Significant
      changes were also not seen in leptin and interleukin 6 (IL-6) concentrations
      after the consumption of LGI or LGL diets. Conclusions: We did not find any
      significant effect of dietary GI or GL on serum concentrations of inflammatory
      cytokines, including hs-CRP, leptin, IL-6, and TNF-alpha in adults. Additional
      RCTs-in particular, feeding trials-are required to shed light on this issue.

PMID- 29635485
TI  - Elotuzumab-induced interstitial lung disease: the first case report.
AB  - Elotuzumab, a humanized immunoglobulin G1 monoclonal antibody targeted against
      signaling lymphocytic activation molecule F7 (SLAMF7), has recently been used in
      combination with lenalidomide and dexamethasone for the treatment of patients
      with relapsed or refractory multiple myeloma. The clinical characteristics of
      drug-induced interstitial lung disease (ILD) due to elotuzumab have not been
      clarified. In this report, we describe a patient with refractory multiple myeloma
      who received elotuzumab in combination with lenalidomide and dexamethasone in
      whom fatigue, fever and diffuse pulmonary infiltration developed. The patient had
      a history of long-term therapy with lenalidomide without pulmonary toxicity.
      Bronchoscopy with bronchoalveolar lavage was negative for infection, and
      transbronchial lung biopsies showed active alveolitis with lymphocytic
      infiltration and myxomatous change of the thick alveolar wall. After the
      discontinuation of elotuzumab and lenalidomide, the patient's clinical symptoms
      gradually improved, and spontaneous remission of the pulmonary infiltration was
      observed. Based on the chest CT and lung pathology findings, the exclusion of
      infection and pulmonary edema, and according to the clinical course, we
      established a diagnosis of drug-induced ILD due to elotuzumab. Clinicians should
      bear in mind the potential for pulmonary toxicity in patients receiving
      elotuzumab-containing therapy.

PMID- 29635488
TI  - Effect of motilin receptor activation on food intake and food timing.
AB  - Background: Motilin plasma concentrations are positively correlated with hunger
      ratings during the fasting state. Moreover, the motilin agonist erythromycin
      stimulates meal requests. Objectives: The first aim of the study was to evaluate
      the effect of erythromycin on ad libitum food intake. The second aim was to study
      the involvement of endogenous motilin and octanoylated ghrelin on voluntary meal
      initiations. Design: Study 1: Fourteen healthy participants were studied twice
      after an overnight fast. Intravenous administration of placebo (saline) or
      erythromycin (40 mg) was given in a double-blind randomized order. Participants
      had the opportunity to eat ad libitum from an excess free-choice buffet (2330
      kcal) for the duration of 1 h. The primary outcome was total caloric intake.
      Study 2: Thirteen healthy participants were studied after an overnight fast.
      Baseline blood samples were collected before a breakfast (245 kcal). After a rest
      period of 90 min, blood samples were collected every 15 min for a duration of 5
      h. During this period, volunteers could request small meal portions (164
      kcal/serving) at time points of their choosing and unlimited in numbers. The
      primary outcome was the determination of plasma concentrations before
      postbreakfast spontaneous meal requests. Results: Ad libitum food intake did not
      differ between placebo and erythromycin groups (difference compared with placebo:
      79 kcal; 95% CI: -245.9, 403.97 kcal; P = 0.3). Octanoylated ghrelin
      concentrations before spontaneous meal requests were, on average, 36% (95% CI:
      5.8%, 65.7%; P = 0.02) higher than values before breakfast, whereas motilin
      concentrations did not increase (6% increase: 95% CI: -5.9%, 17.2% increase; P =
      0.3). Conclusions: Motilin receptor stimulation during the fasting state does not
      affect total caloric intake nor does endogenous motilin stimulate meal requests
      after breakfast in the current study population. This trial was registered at
      www.clinicaltrials.gov as NCT03024879.

PMID- 29635489
TI  - Nitrate, the oral microbiome, and cardiovascular health: a systematic literature
      review of human and animal studies.
AB  - Background: Dietary nitrate is an important source of nitric oxide (NO), a
      molecule critical for cardiovascular health. Nitrate is sequentially reduced to
      NO through an enterosalivary nitrate-nitrite-NO pathway that involves the oral
      microbiome. This pathway is considered an important adjunct pathway to the
      classical l-arginine-NO synthase pathway. Objective: The objective of this study
      was to systematically assess the evidence for dietary nitrate intake and improved
      cardiovascular health from both human and animal studies. Design: A systematic
      literature search was performed according to PRISMA (Preferred Reporting Items
      for Systematic Reviews and Meta-Analyses) guidelines by using key search terms in
      Medline and EMBASE databases and defined inclusion and exclusion criteria.
      Results: Thirty-seven articles on humans and 14 articles on animals were included
      from 12,541 screened references. Data on the effects of dietary nitrate on blood
      pressure, endothelial function, ischemic reperfusion injury, arterial stiffness,
      platelet function, and cerebral blood flow in both human and animal models were
      identified. Beneficial effects of nitrate on vascular health have predominantly
      been observed in healthy human populations, whereas effects in populations at
      risk of cardiovascular disease are less clear. Few studies have investigated the
      long-term effects of dietary nitrate on cardiovascular disease clinical
      endpoints. In animal studies, there is evidence that nitrate improves blood
      pressure and endothelial function, particularly in animal models with reduced NO
      bioavailability. Nitrate dose seems to be a critical factor because there is
      evidence of cross-talk between the 2 pathways of NO production. Conclusions:
      Evidence for a beneficial effect in humans at risk of cardiovascular disease is
      limited. Furthermore, there is a need to investigate the long-term effects of
      dietary nitrate on cardiovascular disease clinical endpoints. Further animal
      studies are required to elucidate the mechanisms behind the observed effects.

PMID- 29635491
TI  - Erratum for Velmurugan et al. Dietary nitrate improves vascular function in
      patients with hypercholesterolemia: a randomized, double-blind, placebo
      controlled study. Am J Clin Nutr 2016;103:25-38.

PMID- 29635490
TI  - Cancer and vitamin D supplementation: a systematic review and meta-analysis.
AB  - Background: Low 25-hydroxyvitamin D status has been associated with a higher risk
      of cancer in epidemiologic studies. Objective: The aim of this study was to
      undertake a systematic review and meta-analysis of randomized clinical trials
      (RCTs) investigating the effect of vitamin D supplementation alone on cancer
      incidence and mortality. Design: A systematic review was undertaken. MEDLINE,
      Embase, CENTRAL, conference abstracts, and clinical trial registries were
      searched (last search March 2017) for RCTs investigating vitamin D
      supplementation alone. RCTs with >=12 mo of follow-up and in participants with a
      mean or median age >=60 y were eligible. During-study events were used as the
      main analysis, but after-study events were included in a secondary analysis.
      Subgroup analyses concerning different forms of vitamin D supplementation, 25
      hydroxyvitamin D status at baseline, vitamin D dose, and exclusion of open-label
      trials were undertaken. Results: Thirty studies in 18,808 participants were
      included in the systematic review, with a median follow-up ranging from 1 to 6.2
      y. The results of the meta-analysis for during-study events showed no evidence of
      an effect of vitamin D supplementation for cancer incidence (RR: 1.03; 95% CI:
      0.91, 1.15) and cancer-related deaths (RR: 0.85; 95% CI: 0.70, 1.04). Including
      after-study events, the RRs were 1.02 (95% CI: 0.92, 1.13) and 0.85 (95% CI:
      0.72, 1.00), respectively. These results did not appear to be affected by
      baseline 25-hydroxyvitamin D status, vitamin D dose, or the exclusion of open
      label trials. Conclusion: We did not find evidence to suggest that vitamin D
      supplementation alone reduces the incidence of cancer or cancer mortality, even
      after including long-term follow-up results.

PMID- 29635492
TI  - Gene-specific DNA methylation in newborns in response to folic acid
      supplementation during the second and third trimesters of pregnancy: epigenetic
      analysis from a randomized controlled trial.
AB  - Background: Emerging evidence suggests that maternal folate status can impact
      cognitive development in childhood. Folate-dependent DNA methylation may provide
      a biological mechanism to link folate status during pregnancy with cognition in
      the offspring. Objective: The objective was to investigate the effect of
      continued folic acid (FA) supplementation beyond the first trimester of pregnancy
      on DNA methylation in cord blood of epigenetically controlled genes related to
      brain development and function. Design: Using available cord blood samples (n =
      86) from the Folic Acid Supplementation in the Second and Third Trimesters
      (FASSTT) trial in pregnancy, we applied pyrosequencing techniques to analyze cord
      blood DNA at 9 candidate loci known to be regulated by methylation, including
      some previously implicated in observational studies: the widely dispersed
      retrotransposon long interspersed nuclear element-1 (LINE-1) and 8 single-copy
      loci (RBM46, PEG3, IGF2, GRB10, BDNF, GRIN3B, OPCML, and APC2). Results: The
      newborns of mothers who received ongoing FA (400 ug/d) through the second and
      third trimesters, compared with placebo, had significantly lower overall DNA
      methylation levels at LINE-1 (56.3% +/- 1.7% compared with 57.2% +/- 2.1%; P =
      0.024), IFG2 (48.9% +/- 4.4% compared with 51.2% +/- 5.1%; P = 0.021), and BDNF
      (2.7% +/- 0.7% compared with 3.1% +/- 0.8%; P = 0.003). The effect of FA
      treatment on DNA methylation was significant only in female offspring for IGF2 (P
      = 0.028) and only in males for BDNF (P = 0.012). For GRB10 and GRIN3B, we
      detected no effect on overall methylation; however, individual cytosine-phosphate
      guanine sites showed significant DNA methylation changes in response to FA.
      Conclusions: Continued supplementation with FA through trimesters 2 and 3 of
      pregnancy results in significant changes in DNA methylation in cord blood of
      genes related to brain development. The findings offer a potential biological
      mechanism linking maternal folate status with neurodevelopment of the offspring,
      but this requires further investigation using a genome-wide approach. This trial
      was registered at www.isrctn.com as ISRCTN19917787.

PMID- 29635493
TI  - Avocado consumption and risk factors for heart disease: a systematic review and
      meta-analysis.
AB  - Background: Nutrients in avocados are associated with cardiovascular benefits.
      Objective: The aim of this study was to determine the effect of avocado intake on
      cardiovascular disease (CVD) risk with the use of a systematic review and meta
      analysis. Design: MEDLINE, Cochrane Central, and Commonwealth Agricultural Bureau
      abstracts were searched from 1946 through September 2017 for publications on
      avocado intake and CVD risk. All designs except for cross-sectional studies that
      evaluated avocado intake were included. Two investigators independently screened
      citations and extracted data. Random-effects models meta-analysis was used when
      >=3 studies reported the same outcome. Results: Of 18 eligible studies (481
      subjects), 7 studies compared avocado intake with no intake, 3 studies compared
      avocado plus monounsaturated fat intake with a control, and 8 studies reported
      data for qualitative synthesis. In 7 studies, avocado intake significantly
      increased HDL cholesterol (summary net change: 2.84 mg/dL; 95% CI: 0.18, 5.49
      mg/dL), with significant heterogeneity. This remained consistent in sensitivity
      and subgroup analyses. There was no significant difference between avocado intake
      and the control for the outcomes of serum total cholesterol (TC), LDL
      cholesterol, triglycerides (TGs), ratios of TC to HDL cholesterol and LDL
      cholesterol to HDL cholesterol, and body weight. In qualitative synthesis, there
      was no significant difference between groups for blood glucose (2 studies),
      homeostasis model assessment (1 of 2 studies), oxidized LDL (2 studies), high
      sensitivity C-reactive protein (2 studies), or apolipoprotein B (2 studies) or,
      in 1 study each, for body mass index, systolic and diastolic blood pressure,
      arterial compliance, fibrinogen, interleukin 6, tumor necrosis factor alpha, and
      serum nitric oxide. No studies reported incident clinical outcomes of CVD,
      including myocardial infarction, stroke, and other clinical endpoints.
      Conclusions: Avocado intake resulted in no difference in serum TC, LDL
      cholesterol, and TG concentrations, but it did increase serum HDL-cholesterol
      concentrations, with significant heterogeneity. The association between avocado
      intake and CVD risk should be confirmed by well-conducted prospective
      observational studies or long-term trials.

PMID- 29635494
TI  - Variety and content of commercial infant and toddler vegetable products
      manufactured and sold in the United States.
AB  - Background: Exposure to vegetable flavors during infancy and toddlerhood is
      hypothesized to enhance vegetable acceptance when children transition to table
      foods. Objective: We sought to examine the vegetable types, ingredients, and
      nutrient contents of vegetable-containing infant and toddler foods (ITFs)
      manufactured and sold in the United States. Design: A database of ITFs that
      contain vegetables (n = 548) was compiled from websites of companies based in the
      United States (n = 24). Product information was recorded, including intended age
      or stage, ingredient lists, and selected nutrients from the Nutrition Facts
      label. Ingredient lists were used to categorize vegetables using the USDA
      vegetable categories: dark green (e.g., spinach), red and orange (e.g., carrots),
      starchy (e.g., green peas, corn), beans and peas (e.g., black beans), and other
      (e.g., green beans, beets). Furthermore, products were categorized as single
      vegetable, multi-vegetable, vegetable and fruit, vegetable and meat, or vegetable
      and other combinations (e.g., grains and and or dairy). Nutrients were examined,
      including energy (kilocalories), carbohydrates, fiber, and total sugars [per
      serving, per 100 g, per reference amount customarily consumed (RACC), and
      percentage of kilocalories from sugars]. Results: Of the 548 vegetable products,
      only 52 single-vegetable products (9.5%) were identified, none of which contained
      dark green vegetables or beans and peas. Red and orange vegetables most often
      appeared as the first ingredient (23.7%) compared to other vegetable types, such
      as dark green vegetables, which were rarely listed first (1.1%). Fruits were
      listed as the first ingredient more commonly than all vegetables (37.8%). One-way
      ANOVA revealed that vegetable and fruit products contained more sugars on average
      than did vegetable products with other ingredients, such as dairy and/or grains
      (all P values < 0.001). Conclusions: Current available products do not provide
      caregivers with a sufficient variety of single-vegetable products or products
      containing dark green vegetables to facilitate children's subsequent acceptance
      of these vegetables. Guidance should include making caregivers aware of the
      limitations of commercial ITFs manufactured and sold in the US market.

PMID- 29635495
TI  - Simulating long-term human weight-loss dynamics in response to calorie
      restriction.
AB  - Background: Mathematical models have been developed to predict body weight (BW)
      and composition changes in response to lifestyle interventions, but these models
      have not been adequately validated over the long term. Objective: We compared
      mathematical models of human BW dynamics underlying 2 popular web-based weight
      loss prediction tools, the National Institutes of Health Body Weight Planner (NIH
      BWP) and the Pennington Biomedical Research Center Weight Loss Predictor (PBRC
      WLP), with data from the 2-year Comprehensive Assessment of Long-term Effects of
      Reducing Intake of Energy (CALERIE) study. Design: Mathematical models were
      initialized using baseline CALERIE data, and changes in body weight (DeltaBW),
      fat mass (DeltaFM), and energy expenditure (DeltaEE) were simulated in response
      to time-varying changes in energy intake (DeltaEI) objectively measured using the
      intake-balance method. No model parameters were adjusted from their previously
      published values. Results: The PBRC WLP model simulated an exaggerated early
      decrease in EE in response to calorie restriction, resulting in substantial
      underestimation of the observed mean (95% CI) BW losses by 3.8 (3.5, 4.2) kg. The
      NIH WLP simulations were much closer to the data, with an overall mean DeltaBW
      bias of -0.47 (-0.92, -0.015) kg. Linearized model analysis revealed that the
      main reason for the PBRC WLP model bias was a parameter value defining how
      spontaneous physical activity expenditure decreased with caloric restriction.
      Both models exhibited substantial variability in their ability to simulate
      individual results in response to calorie restriction. Monte Carlo simulations
      demonstrated that DeltaEI measurement uncertainties were a major contributor to
      the individual variability in NIH BWP model simulations. Conclusions: The NIH BWP
      outperformed the PBRC WLP and accurately simulated average weight-loss and energy
      balance dynamics in response to long-term calorie restriction. However, the
      substantial variability in the NIH BWP model predictions at the individual level
      suggests cautious interpretation of individual-level simulations. This trial was
      registered at clinicaltrials.gov as NCT00427193.

PMID- 29635496
TI  - Breastfeeding duration, maternal body mass index, and birth weight are associated
      with differences in body mass index growth trajectories in early childhood.
AB  - Background: Accelerated postnatal growth is an important predictor for obesity
      risk. It is unknown whether early-life obesity-related risk factors affect body
      mass index (BMI) growth rates during distinct growth periods from early infancy
      through preschool years. Objective: We examined whether breastfeeding duration,
      maternal BMI, and birth weight are associated with growth trajectories of age-
      and sex-standardized WHO BMI z scores (zBMIs) in young children. Design: Children
      (n = 5905) in The Applied Research Group for Kids (TARGet Kids!) prospective
      cohort study underwent repeated measures of weight and length or height from
      birth to 10 y of age. Piecewise linear mixed models were used to determine
      whether zBMI growth rates differ for each risk factor during periods of growth
      between birth and 1, 3, 18, 36, and 72 mo of age. Results: Children who were
      breastfed <6 mo compared with >=6 mo showed a higher growth rate between 1-3 and
      3-18 mo, resulting in higher standardized BMIs (zBMIs) of +0.24, +0.12, and +0.19
      at 18, 36, and 72 mo, respectively. Maternal BMI (in kg/m2) >=30 compared with
      <30 resulted in higher growth rates between 1-3 and 36-72 mo and higher zBMIs of
      +0.22, +0.14, +0.18, and +0.41 at 3, 18, 36, and 72 mo, respectively. Infants
      weighing <2.5 kg at birth (compared with 2.5-4 kg) experienced higher growth
      rates between 1-3 and 3-18 mo but had lower zBMIs at all time points (zBMI: -1.45
      to -0.21). Infants weighing >=4 kg at birth (compared with 2.5-4 kg) had
      significantly lower growth rates in the first 3 mo but higher zBMIs at all time
      points (zBMI: +1.16 to +0.27). Conclusion: Differences in zBMI growth rates by
      breastfeeding duration, maternal BMI, and birth weight are seen in early infancy
      and contribute to differences in zBMI, which persist into midchildhood. This
      trial was registered at www.clinicaltrials.gov as NCT01869530.

PMID- 29635498
TI  - Dietary glucosinolates and risk of type 2 diabetes in 3 prospective cohort
      studies.
AB  - Background: Glucosinolates are a group of phytochemicals that are abundant in
      cruciferous vegetables and precursors of the potentially chemopreventive
      isothiocyanates. Isothiocyanates may reduce oxidative stress and inflammation,
      but little is known regarding the association between glucosinolate intake and
      risk of type 2 diabetes (T2D). Objective: To evaluate the association between the
      intake of glucosinolates and the incidence of T2D in US men and women. Design:
      This prospective cohort study investigated 200,907 women and men [71,256 women
      from the Nurses' Health Study (NHS; 1984-2012), 88,293 women from the NHS II
      (1991-2013), and 41,358 men from the Health Professionals Follow-Up Study (1986
      2012)] who were free of diabetes, cardiovascular disease, and cancer at baseline.
      Diet was assessed using validated semiquantitative food frequency questionnaires.
      Self-reported T2D incidence was confirmed by a supplementary questionnaire.
      Results: During follow-up in the 3 cohorts, we accumulated 4,303,750 person-years
      and 16,567 incident cases of T2D. After adjustment for major lifestyle and
      dietary risk factors for T2D, participants in the highest quintile of total
      glucosinolate intake had a 19% higher risk (95% CI: 13%, 25%; Ptrend < 0.001) of
      T2D than did those in the lowest quintile. The intake of 3 major glucosinolate
      subtypes was consistently and significantly associated with T2D risk, with pooled
      HRs ranging from 1.13 to 1.18 (all Ptrend < 0.001). A significant association was
      also observed between total cruciferous vegetable consumption and T2D (HR: 1.16;
      95% CI :1.07, 1.25; Ptrend < 0.001). These associations persisted in subgroups
      defined by demographic, lifestyle, and other dietary factors. Conclusions:
      Dietary glucosinolate intake was associated with a moderately higher risk of T2D
      in US adults. These results need to be replicated in further investigations,
      including biomarker-based studies. Mechanistic research is also needed to
      understand the relation between exposures to glucosinolates, isothiocyanates, and
      other metabolites with T2D risk. This trial was registered at clinicaltrials.gov
      as NCT03366532.

PMID- 29635497
TI  - Inflammatory potential of the diet and risk of gastric cancer in the European
      Prospective Investigation into Cancer and Nutrition (EPIC) study.
AB  - Background: Chronic inflammation plays a critical role in the pathogenesis of the
      2 major types of gastric cancer. Several foods, nutrients, and nonnutrient food
      components seem to be involved in the regulation of chronic inflammation.
      Objective: We assessed the association between the inflammatory potential of the
      diet and the risk of gastric carcinoma, overall and for the 2 major subsites:
      cardia cancers and noncardia cancers. Design: A total of 476,160 subjects (30%
      men, 70% women) from the European Investigation into Cancer and Nutrition (EPIC)
      study were followed for 14 y, during which 913 incident cases of gastric
      carcinoma were identified, including 236 located in the cardia, 341 in the distal
      part of the stomach (noncardia), and 336 with overlapping or unknown tumor site.
      The dietary inflammatory potential was assessed by means of an inflammatory score
      of the diet (ISD), calculated with the use of 28 dietary components and their
      corresponding inflammatory scores. The association between the ISD and gastric
      cancer risk was estimated by HRs and 95% CIs calculated by multivariate Cox
      regression models adjusted for confounders. Results: The inflammatory potential
      of the diet was associated with an increased risk of gastric cancer. The HR (95%
      CI) for each increase in 1 SD of the ISD were 1.25 (1.12, 1.39) for all gastric
      cancers, 1.30 (1.06, 1.59) for cardia cancers, and 1.07 (0.89, 1.28) for
      noncardia cancers. The corresponding values for the highest compared with the
      lowest quartiles of the ISD were 1.66 (1.26, 2.20), 1.94 (1.14, 3.30), and 1.07
      (0.70, 1.70), respectively. Conclusions: Our results suggest that low-grade
      chronic inflammation induced by the diet may be associated with gastric cancer
      risk. This pattern seems to be more consistent for gastric carcinomas located in
      the cardia than for those located in the distal stomach. This study is listed on
      the ISRCTN registry as ISRCTN12136108.

PMID- 29635499
TI  - Neither body mass nor sex influences beverage hydration index outcomes during
      randomized trial when comparing 3 commercial beverages.
AB  - Background: The beverage hydration index (BHI) assesses the hydration potential
      of any consumable fluid relative to water. The BHI is a relatively new metric,
      and the impact of body mass, sex, and reproducibility has yet to be investigated.
      Objectives: To assess the independent impact of body mass and sex on BHI using
      beverages not previously assessed, including an amino acid-based oral rehydration
      solution (AA-ORS), a glucose-containing ORS (G-ORS), and a sports drink (SpD),
      compared with water (control). The reproducibility of the results was examined
      using statistical modeling (bootstrap analysis). Design: Using a repeated
      measures design, 40 euhydrated and fasted subjects (17 male, 23 female; urine
      specific gravity <1.025) were studied on 4 separate occasions. During each trial,
      subjects ingested 1 L of each beverage, and urine output was measured immediately
      postingestion and at 1-h intervals for the next 4 h. The BHI was calculated as a
      ratio of each individual's cumulative urine output after drinking 1 L of water
      over their cumulative urine output after drinking each of the test beverages.
      Results: The calculated mean +/- SD BHIs of the beverages were as follows: water
      (1.0 +/- 0.0), AA-ORS (1.15 +/- 0.28), G-ORS (1.21 +/- 0.28), and SpD (1.09 +/-
      0.26). The BHI for both AA-ORS and G-ORS was greater than that for water (P <
      0.05). Despite overall differences in body mass, neither body mass nor sex
      independently affected BHI. Based upon statistical modeling, our results
      demonstrate excellent reproducibility of outcomes and external validity.
      Conclusions: Our results suggest that the BHI may be used and interpreted with
      confidence independently of body mass or sex. Furthermore, a novel carbohydrate
      free AA-ORS and a traditional commercially available G-ORS were superior to water
      in optimizing hydration, whereas SpD was not. This trial was registered at
      clinicaltrials.gov as NCT03262597.

PMID- 29635500
TI  - Normal-weight obesity and clinical outcomes in nondiabetic chronic kidney disease
      patients: a cohort study.
AB  - Background: Normal-weight obesity (NWO), defined by a normal body mass index
      (BMI) and high body fat percentage, has been shown to be associated with
      cardiometabolic dysfunction and an increased risk of cardiovascular disease and
      mortality in the general population. However, little is known about the clinical
      implications of NWO among patients with chronic kidney disease (CKD). Objective:
      The aim of this study was to assess the characteristics and outcomes of
      nondiabetic CKD patients with NWO. Design: A total of 178 nondiabetic patients
      with stages 3-5 CKD were prospectively followed for a median of 4.9 y. The
      patients were classified into 3 different adiposity phenotypes: nonobese [BMI (in
      kg/m2) <25 and fat mass percentage (FM%) <=25% for men or <=35% for women], NWO
      (BMI <25 and FM% >25% for men or >35% for women), and preobese-obese (BMI >=25).
      FM% was determined using the Body Composition Monitor, a multifrequency
      bioimpedance spectroscopy device. The outcome was a composite of cardiovascular
      events or all-cause mortality. Results: The prevalence of NWO was 28.1% among
      nondiabetic CKD patients with a normal BMI. NWO patients were older, had lower
      lean body mass, and had higher plasma interleukin-6 concentrations than nonobese
      patients. However, homeostatic model assessment for insulin resistance levels did
      not differ between the 2 groups. NWO patients showed a significant 3-fold higher
      risk of the composite outcome (HR 2.96, 95% CI: 1.13, 7.77; P < 0.05) than did
      nonobese patients in the fully adjusted model. Preobese-obese patients were not
      at increased risk compared to nonobese patients. Conclusions: NWO was associated
      with the worst prognosis among the 3 different adiposity phenotypes in
      nondiabetic CKD patients. Our findings suggest the importance of using direct
      measures of adiposity for risk assessment in CKD patients who are normal-weight.
      This trial was registered at clinicaltrials.gov as NCT03285074.

PMID- 29635502
TI  - Infant feeding and growth: putting the horse before the cart.
AB  - Background: Previous observational studies have consistently shown slower weight
      and length gains in infants with prolonged breastfeeding than in those who were
      formula-fed from birth or breastfed for a shorter duration. These studies
      inferred that prolonged breastfeeding causes slower growth in infancy. Objective:
      We compared infant growth associated with >=12 mo of breastfeeding with a shorter
      duration of breastfeeding on the basis of 3 different analytic approaches to the
      same data from a randomized trial: intention-to-treat (ITT; "as randomized"),
      observational ("as fed"), and instrumental variable (IV; by using randomization
      as an "instrument" to achieve >=12 mo of breastfeeding). Design: This was a
      cluster-randomized trial of a breastfeeding-promotion intervention.
      Anthropometric measurements were obtained at birth and at 1, 2, 3, 6, 9, and 12
      mo. Results: The 3 analytic approaches yielded different results. The ITT
      approach showed more rapid growth in the first 2 mo among infants randomly
      assigned to the breastfeeding-promotion intervention than among control infants,
      with a decreasing difference over the ensuing months and nearly identical weight,
      length, and body mass index by 12 mo. The observational analysis showed a
      different trend: higher weight and length in infants who were breastfed >=12 mo
      than in those who were breastfed <12 mo during the first 3 mo and no difference
      by 6 mo, while infants who were breastfed <12 mo showed increasingly higher
      weight and length from 6 to 12 mo. The IV analysis showed a temporal pattern that
      was similar to that seen in the ITT analysis, but with larger (and less precise)
      differences between infants breastfed for >=12 compared with <12 mo. Conclusions:
      We observed major differences in experimental (ITT and IV) compared with
      observational approaches to analyzing data obtained from the same children. These
      approaches lead to opposite causal inferences about the relation between infant
      feeding and growth and underline the importance of ensuring that the postulated
      cause (feeding) temporally precedes its hypothesized effect (growth). This trial
      is registered at http://www.isrctn.org/ as ISRCTN37687716.

PMID- 29635501
TI  - Changes in susceptibility to life-threatening infections after treatment for
      complicated severe malnutrition in Kenya.
AB  - Background: Goals of treating childhood severe acute malnutrition (SAM), in
      addition to anthropometric recovery and preventing short-term mortality, include
      reducing the risks of subsequent serious infections. How quickly and how much the
      risk of serious illness changes during rehabilitation are unknown but could
      inform improving the design and scope of interventions. Objective: The aim of
      this study was to investigate changes in the risk of life-threatening events
      (LTEs) in relation to anthropometric recovery from SAM. Design: This was a
      secondary analysis of a clinical trial including 1778 HIV-uninfected Kenyan
      children aged 2-59 mo with complicated SAM, enrolled after the inpatient
      stabilization phase of treatment, and followed for 12 mo. The main outcome was
      LTEs, defined as infections requiring rehospitalization or causing death. We
      examined anthropometric variables measured at months 1, 3, and 6 after enrollment
      in relation to LTEs occurring during the 6 mo after each of these time points.
      Results: Over 12 mo, there were 823 LTEs (257 fatal), predominantly severe
      pneumonia and diarrhea. At months 1, 3, and 6, 557 (34%), 764 (49%), and 842
      (56%) children had a weight-for-height or -length z score (WHZ) >=-2,
      respectively, which, compared with a WHZ <-3, was associated with lower risks of
      subsequent LTEs [adjusted HRs (95% CIs): 0.50 (0.40, 0.64), 0.30 (0.23, 0.39),
      and 0.23 (0.16, 0.32), respectively]. However, children with a WHZ >=-2 at 1, 3,
      and 6 mo still had 39 (95% CI: 32, 47), 26 (95% CI: 22, 32), and 15 (95% CI: 12,
      20) LTEs/100 child-years of observation during the following 6 mo. WHZ at study
      enrollment predicted subsequent WHZ but not the risk of LTEs. Changes in height
      for-age z score did not predict LTEs. Conclusions: Anthropometric response was
      associated with a rapid and substantial reduction in risk of LTEs. However,
      reduction in susceptibility lagged behind anthropometric improvement. Disease
      events, together with anthropometric assessment, may provide a clearer picture of
      the effectiveness of interventions. Robust protocols for detecting and treating
      poor anthropometric recovery and addressing broader vulnerabilities that
      complicated SAM indicates may save lives. This trial was registered at
      www.clinicaltrials.gov as NCT00934492.

PMID- 29635503
TI  - Portion size and later food intake: evidence on the "normalizing" effect of
      reducing food portion sizes.
AB  - Background: Historical increases in the size of commercially available food
      products have been linked to the emergence of a worldwide obesity crisis.
      Although the acute effect that portion size has on food intake is well
      established, the effect that exposure to smaller portion sizes has on future
      portion size selection has not been examined. Objective: We tested whether
      reducing a food portion size "renormalizes" perceptions of what constitutes a
      normal amount of that food to eat and results in people selecting and consuming
      smaller portions of that food in the future. Design: Across 3 experiments,
      participants were served a larger or smaller portion of food. In experiments 1
      and 2, participants selected and consumed a portion of that food 24 h later. In
      experiment 3, participants reported on their preferred ideal portion size of that
      food after 1 wk. Results: The consumption of a smaller, as opposed to a larger,
      portion size of a food resulted in participants believing a "normal"-sized
      portion was smaller (experiments 1-3, P <= 0.001), consuming less of that food 1
      d later (experiments 1-2, P <= 0.003), and displaying a tendency toward choosing
      a smaller ideal portion of that food 1 wk later (experiment 3, P = 0.07),
      although the latter finding was not significant. Conclusion: Because consumer
      preferences appear to be driven by environmental influences, reducing food
      portion sizes may recalibrate perceptions of what constitutes a "normal" amount
      of food to eat and, in doing so, decrease how much consumers choose to eat. This
      trial was registered at www.clinicaltrials.gov as NCT03241576.

PMID- 29635504
TI  - Identifying the effect of shelf nutrition labels on consumer purchases: results
      of a natural experiment and consumer survey.
AB  - Background: NuVal, developed by NuVal, LLC, is a shelf nutrition label that rates
      the nutritional quality of foods on a scale of 1 (worst) to 100 (best).
      Objective: The objective of this study was to explore the impact of the NuVal
      labels on food-purchasing patterns. Design: In 2014, NuVal updated its nutrient
      profiling system, which changed the NuVal score on many foods. We took advantage
      of this "natural experiment" to assess the extent to which a change in the NuVal
      score influenced purchases of yogurts, a category with a wide range of more and
      less healthy alternatives. We supplemented these data with a survey of consumers
      in stores using NuVal labels to obtain their experience with the labels and the
      extent to which they state that the labels influence their purchases. Results:
      Results suggested that a 1-point increase in the NuVal score is associated with a
      0.49% increase in sales. Because only 8% of survey respondents reported using
      NuVal to influence dairy purchases, the impact of a change in the score among
      users may be >10 times the average effect. Conclusion: Results suggest that front
      of-package nutrition labels are likely to influence purchasing patterns. This
      trial was registered at www.clinicaltrials.gov as NCT03390075.

PMID- 29635505
TI  - A small dose of whey protein co-ingested with mixed-macronutrient breakfast and
      lunch meals improves postprandial glycemia and suppresses appetite in men with
      type 2 diabetes: a randomized controlled trial.
AB  - Background: Large doses of whey protein consumed as a preload before single high
      glycemic load meals has been shown to improve postprandial glycemia in type 2
      diabetes. It is unclear if this effect remains with smaller doses of whey co
      ingested at consecutive mixed-macronutrient meals. Moreover, whether hydrolyzed
      whey offers further benefit under these conditions is unclear. Objective: The aim
      of this study was to investigate postprandial glycemic and appetite responses
      after small doses of intact and hydrolyzed whey protein co-ingested with mixed
      nutrient breakfast and lunch meals in men with type 2 diabetes. Design: In a
      randomized, single-blind crossover design, 11 men with type 2 diabetes [mean +/-
      SD age: 54.9 +/- 2.3 y; glycated hemoglobin: 6.8% +/- 0.3% (51.3 +/- 3.4
      mmol/mol)] attended the laboratory on 3 mornings and consumed 1) intact whey
      protein (15 g), 2) hydrolyzed whey protein (15 g), or 3) placebo (control)
      immediately before mixed-macronutrient breakfast and lunch meals, separated by 3
      h. Blood samples were collected periodically and were processed for insulin,
      intact glucagon-like peptide 1 (GLP-1), gastric inhibitory polypeptide (GIP),
      leptin, peptide tyrosine tyrosine (PYY3-36), and amino acid concentrations.
      Interstitial glucose was measured during and for 24 h after each trial.
      Subjective appetite was assessed with the use of visual analog scales. Results:
      Total postprandial glycemia area under the curve was reduced by 13% +/- 3% after
      breakfast following the intact whey protein when compared with control (P <
      0.05). Hydrolyzed whey attenuated early glucose after breakfast when compared
      with control (P < 0.05). Glycemia was improved postlunch after the intact whey
      protein only when compared with control (P < 0.05). Greater satiety was observed
      after the intact whey protein only after both meals when compared with control (P
      < 0.05). Insulin concentrations increased after both the intact and hydrolyzed
      whey protein, showing strong positive correlations with increases in valine and
      isoleucine (P < 0.05). Incretin and appetite regulatory hormone responses were
      similar across trials (P > 0.05). Conclusions: The consumption of a small 15-g
      dose of intact whey protein immediately before consecutive mixed-macronutrient
      meals improves postprandial glycemia, stimulates insulin release, and increases
      satiety in men with type 2 diabetes. This trial was registered at
      www.clinicialtrials.gov as NCT02903199.

PMID- 29635506
TI  - The challenge of meeting prescribed carbohydrate intake goals in low-carbohydrate
      diet studies.

PMID- 29635507
TI  - Reply to JN Orloff et al.

PMID- 29635508
TI  - Corrigendum for Al Khatib et al. Sleep extension is a feasible lifestyle
      intervention in free-living adults who are habitually short sleepers: a potential
      strategy for decreasing intake of free sugars? A randomized controlled pilot
      study. Am J Clin Nutr 2018;107:43-53.

PMID- 29635509
TI  - Evidence on the "normalizing" effect of reducing food-portion sizes.

PMID- 29635510
TI  - Folic acid throughout pregnancy: too much?

PMID- 29635511
TI  - Breastfeeding newborns and infants: some new food for thought about an old
      practice.

PMID- 29635512
TI  - Using total knee arthroplasty as a primary outcome measure is too "hard" in
      lifestyle intervention trials in osteoarthritis.

PMID- 29635514
TI  - PROFICIENCY TEST OF THE SSDL-ININ-MEXICO FOR THE CALIBRATION OF WELL-TYPE
      CHAMBERS WITH HDR 192IR SOURCES USING TWO DIFFERENT DOSIMETRY CODES OF PRACTICE
      FOR THE DETERMINATION OF REFERENCE AIR KERMA RATE KR.
AB  - The results of the comparison between SSDL-ININ and SSDL-CPHR (pilot laboratory)
      demonstrates the competence of the SSDL-ININ for the performance of the KR in
      192Ir. The RININ/CHPR ratio for the calibration coefficients is 0.989 +/- 0.005.
      The comparison uses three SI-HDR 1000-Plus as transfer chambers, series: A02423,
      A941755 and A973052. CPHR used a secondary standard PTW 3304 chamber, s/n 154,
      calibrated at PTB and ININ employed a secondary standard SI-90008 s/n A963391,
      calibrated at NPL. To determine KR, the SSDL-CPHR used the IAEA TEC-DOC-1274 and
      the SSDL-ININ used the IPEM (UK) code of practice. The latter uses a correction
      factor by source's geometry, ksg. The results show that both codes are
      equivalent; however, for the use of well chambers in the highlands or in
      locations with reduced atmospheric pressure, it is needed to apply an additional
      factor k'P, or, to design a well chamber with air-equivalent walls for the
      application of the conventional kPT.

PMID- 29635513
TI  - SNX14 mutations affect endoplasmic reticulum-associated neutral lipid metabolism
      in autosomal recessive spinocerebellar ataxia 20.
AB  - Mutations in SNX14 cause the autosomal recessive cerebellar ataxia 20 (SCAR20).
      Mutations generally result in loss of protein although several coding region
      deletions have also been reported. Patient-derived fibroblasts show disrupted
      autophagy, but the precise function of SNX14 is unknown. The yeast homolog, Mdm1,
      functions in endoplasmic reticulum (ER)-lysosome/vacuole inter-organelle
      tethering, but functional conservation in mammals is still required. Here, we
      show that loss of SNX14 alters but does not block autophagic flux. In addition,
      we find that SNX14 is an ER-associated protein that functions in neutral lipid
      homeostasis and inter-organelle crosstalk. SNX14 requires its N-terminal
      transmembrane helices for ER localization, while the Phox homology (PX) domain is
      dispensable for subcellular localization. Both SNX14-mutant fibroblasts and
      SNX14KO HEK293 cells accumulate aberrant cytoplasmic vacuoles, suggesting defects
      in endolysosomal homeostasis. However, ER-late endosome/lysosome contact sites
      are maintained in SNX14KO cells, indicating that it is not a prerequisite for ER
      endolysosomal tethering. Further investigation of SNX14- deficiency indicates
      general defects in neutral lipid metabolism. SNX14KO cells display distinct
      perinuclear accumulation of filipin in LAMP1-positive lysosomal structures
      indicating cholesterol accumulation. Consistent with this, SNX14KO cells display
      a slight but detectable decrease in cholesterol ester levels, which is
      exacerbated with U18666A. Finally, SNX14 associates with ER-derived lipid
      droplets (LD) following oleate treatment, indicating a role in ER-LD crosstalk.
      We therefore identify an important role for SNX14 in neutral lipid homeostasis
      between the ER, lysosomes and LDs that may provide an early intervention target
      to alleviate the clinical symptoms of SCAR20.

PMID- 29635515
TI  - Defensive medicine among antibiotic stewards: the international ESCMID
      AntibioLegalMap survey.
AB  - Objectives: To investigate fear of legal claims and defensive behaviours among
      specialists in infectious diseases (ID) and clinical microbiology (CM) and to
      identify associated demographic and professional characteristics. Methods:
      AntibioLegalMap was an international cross-sectional internet-based survey
      targeting specialists in ID and CM. Three variables were explored: fear of legal
      liability in antibiotic prescribing/advising on antibiotic prescription;
      defensive behaviours in antibiotic prescribing; and defensive behaviours in
      advising. A multivariable logistic regression analysis was performed to identify
      factors significantly associated with each of the three variables. Results: Eight
      hundred and thirty individuals from 74 countries participated. Only 0.4% (3/779)
      had any kind of condemnation for malpractice related to antibiotic prescription.
      Concerning the fear of liability, 21.2% (164/774) of respondents said they never
      worried, 45.1% (349/774) sometimes worried and 28.6% (221/774) frequently worried
      when prescribing/advising on antibiotic prescription. Being female, younger than
      or equal to 35 years and aware of previous cases of litigation were independently
      associated with fear. Most respondents (85.0%, 525/618) reported some defensive
      behaviour in antibiotic prescribing. These behaviours were independently
      associated with being younger than or equal to 35 years and sometimes or often
      worried about liability. Similarly, 76.4% (505/661) reported defensive behaviours
      in advising. These behaviours were associated with being sometimes or often
      worried about liability. The preferred measures to reduce fear and defensive
      behaviours were having local guidelines and sharing decisions through teamwork.
      Conclusions: A significant proportion of specialists in ID and CM reported some
      form of defensive behaviour in prescribing or advising to prescribe antibiotics.
      Defensive medicine should be considered when implementing antibiotic stewardship
      programmes.

PMID- 29635517
TI  - S100A12 and S100A8/9 proteins are biomarkers of articular disease activity in
      Blau syndrome.
AB  - Objective: To identify biomarkers of articular and ocular disease activity in
      patients with Blau syndrome (BS). Methods: Multiplex plasma protein arrays were
      performed in five BS patients and eight normal healthy volunteers (NHVs). Plasma
      S100A12 and S100A8/9 were subsequently measured by ELISA at baseline and 1-year
      follow-up in all patients from a prospective multicentre cohort study. CRP was
      measured using Meso Scale Discovery immunoassay. Active joint counts,
      standardization uveitis nomenclature for anterior uveitis cells and vitreous haze
      by Nussenblatt scale were the clinical parameters. Results: Multiplex Luminex
      arrays identified S100A12 as the most significantly elevated protein in five
      selected BS vs eight NHVs and this was confirmed by ELISA on additional samples
      from the same five BS patients. In the patient cohort, S100A12 (n = 39) and
      S100A8/9 (n = 33) were significantly higher compared with NHVs (n = 44 for
      S100A12, n = 40 for S100A8/9) (P = 0.0000004 and P = 0.0003, respectively).
      Positive correlations between active joint counts and S100 levels were
      significant for S100A12 (P = 0.0008) and S100A8/9 (P = 0.015). CRP levels did not
      correlate with active joint count. Subgroup analysis showed significant
      association of S100 proteins with active arthritis (S100A12 P = 0.01, S100A8/9 P
      = 0.008). Active uveitis was not associated with increased S100 levels.
      Conclusion: S100 proteins are biomarkers of articular disease activity in BS and
      potential outcome measures in future clinical trials. As secreted neutrophil and
      macrophage products, S100 proteins may reflect the burden of granulomatous tissue
      in BS.

PMID- 29635516
TI  - Metabolomic studies identify changes in transmethylation and polyamine metabolism
      in a brain-specific mouse model of tuberous sclerosis complex.
AB  - Tuberous sclerosis complex (TSC) is an autosomal dominant neurodevelopmental
      disorder and the quintessential disorder of mechanistic Target of Rapamycin
      Complex 1 (mTORC1) dysregulation. Loss of either causative gene, TSC1 or TSC2,
      leads to constitutive mTORC1 kinase activation and a pathologically anabolic
      state of macromolecular biosynthesis. Little is known about the organ-specific
      metabolic reprogramming that occurs in TSC-affected organs. Using a mouse model
      of TSC in which Tsc2 is disrupted in radial glial precursors and their neuronal
      and glial descendants, we performed an unbiased metabolomic analysis of
      hippocampi to identify Tsc2-dependent metabolic changes. Significant metabolic
      reprogramming was found in well-established pathways associated with mTORC1
      activation, including redox homeostasis, glutamine/tricarboxylic acid cycle,
      pentose and nucleotide metabolism. Changes in two novel pathways were identified:
      transmethylation and polyamine metabolism. Changes in transmethylation included
      reduced methionine, cystathionine, S-adenosylmethionine (SAM-the major methyl
      donor), reduced SAM/S-adenosylhomocysteine ratio (cellular methylation
      potential), and elevated betaine, an alternative methyl donor. These changes were
      associated with alterations in SAM-dependent methylation pathways and expression
      of the enzymes methionine adenosyltransferase 2A and cystathionine beta synthase.
      We also found increased levels of the polyamine putrescine due to increased
      activity of ornithine decarboxylase, the rate-determining enzyme in polyamine
      synthesis. Treatment of Tsc2+/- mice with the ornithine decarboxylase inhibitor
      alpha-difluoromethylornithine, to reduce putrescine synthesis dose-dependently
      reduced hippocampal astrogliosis. These data establish roles for SAM-dependent
      methylation reactions and polyamine metabolism in TSC neuropathology.
      Importantly, both pathways are amenable to nutritional or pharmacologic therapy.

PMID- 29635518
TI  - Presence of aggregates of smooth endoplasmic reticulum in MII oocytes affects
      oocyte competence: molecular-based evidence.
AB  - STUDY QUESTION: Does the presence of aggregates of smooth endoplasmic reticulum
      (SERa) impact the transcriptome of human metaphase II (MII) oocytes?. SUMMARY
      ANSWER: The presence of SERa alters the molecular status of human metaphase II
      oocytes. WHAT IS KNOWN ALREADY: Oocytes presenting SERa are considered
      dysmorphic. Oocytes with SERa (SERa+) have been associated with reduced
      embryological outcome and increased risk of congenital anomalies, although some
      authors have reported that SERa+ oocytes can lead to healthy newborns. The
      question of whether or not SERa+ oocytes should be discarded is still open for
      debate, and no experimental information about the effect of the presence of SERa
      on the oocyte molecular status is available. STUDY DESIGN, SIZE, DURATION: This
      study included 28 women, aged <38 years, without any ovarian pathology, and
      undergoing IVF treatment. Supernumerary MII oocytes with no sign of morphological
      alterations as well as SERa+ oocytes were donated after written informed consent.
      A total of 31 oocytes without SERa (SERa-) and 24 SERa+ oocytes were analyzed.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: Pools of 8-10 oocytes for both group
      were prepared. Total RNA was extracted from each pool, amplified, labeled and
      hybridized on oligonucleotide microarrays. Analyses were performed by R software
      using the limma package. MAIN RESULTS AND THE ROLE OF CHANCE: The expression
      profiles of SERa+ oocytes significantly differed from those of SERa- oocytes in
      488 probe sets corresponding to 102 down-regulated and 283 up-regulated unique
      transcripts. Gene Ontology analysis by DAVID bioinformatics disclosed that genes
      involved in three main biological processes were significantly down-regulated in
      SERa+ oocytes respective to SERa- oocytes: (i) cell and mitotic/meiotic nuclear
      division, spindle assembly, chromosome partition and G2/M transition of mitotic
      cell cycle; (ii) organization of cytoskeleton and microtubules; and (iii)
      mitochondrial structure and activity. Among the transcripts up-regulated in SERa+
      oocytes, the most significantly (P = 0.002) enriched GO term was 'GoLoco motif',
      including the RAP1GAP, GPSM3 and GPSM1 genes. LARGE SCALE DATA: Raw microarray
      data are accessible through GEO Series accession number GSE106222
      (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE106222). LIMITATIONS,
      REASONS FOR CAUTION: Data validation in a larger cohort of samples would be
      beneficial, although we applied stringent criteria for gene selection (fold
      change >3 or <1/3 and FDR < 0.1). Surveys on clinical outcomes, malformation
      rates and follow-up of babies born after transfer of embryos from SERa+ oocytes
      are necessary. WIDER IMPLICATIONS OF THE FINDINGS: We provide information on the
      molecular status of SERa+ oocytes, highlighting possible associations between
      presence of SERa, altered oocyte physiology and reduced developmental competence.
      Our study may offer further information that can assist embryologists to make
      decisions on whether, and with what possible implications, SERa+ oocytes should
      be used. We believe that the presence of SERa should be still a 'red flag' in IVF
      practices and that the decision to inseminate SERa+ oocytes should be discussed
      on a case-by-case basis. STUDY FUNDING/COMPETING INTEREST(s): This study was
      partially supported by Ferring Pharmaceuticals. The authors have no conflicts of
      interest to declare.

PMID- 29635519
TI  - CoERG11 A395T mutation confers azole resistance in Candida orthopsilosis clinical
      isolates.
AB  - Background: Candida orthopsilosis is a human fungal pathogen responsible for a
      wide spectrum of symptomatic infections. Evidence suggests that C. orthopsilosis
      is mainly susceptible to azoles, the most extensively used antifungals for
      treatment of these infections. However, fluconazole-resistant clinical isolates
      are reported. Objectives: This study evaluated the contribution of a single amino
      acid substitution in the azole target CoErg11 to the development of azole
      resistance in C. orthopsilosis. Methods: C. orthopsilosis clinical isolates (n =
      40) were tested for their susceptibility to azoles and their CoERG11 genes were
      sequenced. We used a SAT1 flipper-driven transformation to integrate a mutated
      CoERG11 allele in the genetic background of a fluconazole-susceptible isolate.
      Results: Susceptibility testing revealed that 16 of 40 C. orthopsilosis clinical
      isolates were resistant to fluconazole and to at least one other azole. We
      identified an A395T mutation in the CoERG11 coding sequence of azole-resistant
      isolates only that resulted in the non-synonymous amino acid substitution Y132F.
      The SAT1 flipper cassette strategy led to the creation of C. orthopsilosis
      mutants that carried the A395T mutation in one or both CoERG11 alleles
      (heterozygous or homozygous mutant, respectively) in an azole-susceptible genetic
      background. We tested mutant strains for azole susceptibility and for hot-spot
      locus heterozygosity. Both the heterozygous and the homozygous mutant strains
      exhibited an azole-resistant phenotype. Conclusions: To the best of our
      knowledge, these findings provide the first evidence that the CoErg11 Y132F
      substitution confers multi-azole resistance in C. orthopsilosis.

PMID- 29635520
TI  - Symptomatic Adjacent Level Disease Requiring Surgery: Analysis of 10-Year Results
      From a Prospective, Randomized, Clinical Trial Comparing Cervical Disc
      Arthroplasty to Anterior Cervical Fusion.
AB  - BACKGROUND: Ten-year follow-up data from the US Food and Drug Administration
      investigational device exemption trial comparing BRYAN(r) Cervical Disc
      (Medtronic, Dublin, Ireland) arthroplasty to anterior cervical discectomy and
      fusion (ACDF) demonstrated that disc arthroplasty maintained range of motion and
      improvements in overall success and neck disability. OBJECTIVE: To compare the 10
      yr rates of symptomatic adjacent level disease requiring surgery (SALDRS).
      METHODS: Prospective randomized trial data were analyzed comparing BRYAN(r)
      Cervical Disc arthroplasty to ACDF for single-level cervical disc disease with
      concordant radiculopathy or myelopathy with clinicoradiographic analysis at 10
      yr. Secondarily, 84-mo data were pooled with PRESTIGE(r) Cervical Disc
      arthroplasty (Medtronic) study data to provide overall rates of SALDRS. RESULTS:
      Significantly greater overall success was maintained at every postoperative
      interval with an overall success rate of 81.3% with BRYAN(r) disc and 66.3% with
      ACDF (P = .005) without loss of motion preservation (8.69 degrees  vs 0.60
      degrees ). Reoperation at adjacent levels up to the 120-mo visit was 9.7% in the
      arthroplasty group and 15.8% in the ACDF group (P = .146). The combined data from
      BRYAN(r) and Prestige ST demonstrate that BRYAN(r) and Prestige disc groups had a
      lower rate of second surgeries at the adjacent levels, up to the 84-mo visit,
      compared to the combined ACDF groups (6.9% vs 11.7%; P = .023). CONCLUSION:
      Compared with ACDF, fewer patients with the BRYAN(r) disc required surgery for
      symptomatic adjacent level degeneration, but this did not achieve statistical
      significance. Analysis of combined study data using Bryan and Prestige discs
      shows significant differences in SADLRS as early as 7 yr.

PMID- 29635521
TI  - Getting the balance right-tackling the obesogenic environment by reducing
      unhealthy options in a hospital shop without affecting profit.
AB  - Background: UK hospitals have been criticized for fuelling obesity by allowing
      contracts with food retailers selling high fat and high-sugar products on
      hospital premises. Methods: We assessed the impact for a major retailer of
      increasing healthy food choices at their Royal Free London NHS Foundation Trust
      outlet. To assess the impact on sales, profit and acceptability to customers, a
      multi-component intervention based on behavioural insights theory was enacted
      over 2 months (November-December 2014) at the Royal Free site WHSmith. Sales data
      on all food and drink were assessed over three time periods: (i) 2 months
      immediately prior to, and (ii) immediately after the intervention, and (iii) the
      equivalent period 10 months later. Acceptability to customers was assessed via
      questionnaires, and profit assessed as a proxy for retailer satisfaction.
      Results: Compared to the pre-intervention period, total sales increased
      immediately after the intervention, and again 10 months after the intervention.
      Sales of healthier options increased as a proportion of total sales following the
      intervention, sales of sweets and chocolates decreased, while the relative sales
      of other items remained similar. Conclusions: We demonstrated that healthier
      alternatives could be provided in a hospital retail premises without negatively
      affecting total sales, retailer or customer satisfaction.

PMID- 29635522
TI  - Contemporary Factors Associated with the Use of Laparoscopy for Inguinal Hernia
      Repair Among Department of Defense Beneficiaries.
AB  - Introduction: The factors that contribute to variation in utilization of
      laparoscopic inguinal hernia repair are unknown. We sought to determine the
      current usage patterns of laparoscopic and open surgery in the elective repair of
      uncomplicated unilateral inguinal hernia in a large population with universal
      health care coverage comprised of Department of Defense (DoD) beneficiaries.
      Materials and methods: The DoD Military Health System Data Repository (MDR)
      tracks health care delivered to a universally insured population of
      active/reserve/retired members of the U.S. Armed Services and their dependents.
      The MDR was queried for elective unilateral inguinal hernia repair among adult
      patients between 2008 and 2014. The primary outcome was laparoscopic (vs. open)
      approach to hernia repair. We conducted univariable and multivariable analyses of
      patient- and systems-level factors associated with approach to inguinal hernia
      repair. This research was approved by our institutional review board prior to
      commencement of the study and need for informed consent was waived given the
      design of this study. Results: Among 37,742 elective uncomplicated unilateral
      inguinal hernia repairs, 35% (n = 13,114) were performed laparoscopically. In
      2014, 40% of inguinal hernia repairs were performed laparoscopically, compared
      with 27% of repairs in 2008 (P < 0.01). In multivariable analysis, laparoscopic
      hernia repair was more likely for male patients (OR = 1.38, 95% CI = 1.23-1.54, P
      < 0.01), military (vs. civilian) institutions (OR = 1.34, 95% CI = 1.28-1.41, P <
      0.01), active-duty officers (vs. active-duty enlisted; OR = 1.21, 95% CI = 1.12
      1.30, P < 0.01), and more recent year of surgery (P < 0.01). Laparoscopic repair
      was significantly less likely among patients with greater than one comorbidity
      (vs. none; OR = 0.68, 95% CI = 0.61-0.76, P < 0.01). Conclusion: In a large,
      universally insured population of military service members and their dependents,
      laparoscopic inguinal repair is increasingly used and was preferred over open
      repair for younger, healthier, active-duty patients and those treated within the
      military (vs. non-military) care system.

PMID- 29635523
TI  - Early Tympanoplasty Using a Synthetic Biomembrane for Military-Related Blast
      Induced Large Tympanic Membrane Perforation.
AB  - Introduction: Blast injuries in modern warfare are common, and tympanic
      perforation is often found. Spontaneous closures of large perforations that
      encompass greater than 80% of the tympanic surface are rare. Early closure of the
      tympanic membrane avoids the immediate infectious risk, which potentially
      complicates the initial management of these war-wounded patients, and allows for
      safe and early recovery of military activity. This study compared the outcomes of
      spontaneous closures and early biomembrane myringoplasty in subjects with large
      blast injury-induced tympanic perforation following a massive explosion.
      Materials and Methods: This is a retrospective, observational, cohort study
      military troops with large barotraumatic tympanic membrane perforation. The study
      investigates early surgical tympanoplasty versus observation for spontaneous
      closure. The hearing loss, tympanic perforation closure rate, and closure time
      were noted. Results: Fourteen patients (19 ears) were referred from May 2008 to
      April 2017, and 6 patients (9 ears) underwent early myringoplasty. A total of 89%
      (n = 8) and 100% (n = 9) of the ears exhibited successful sealing of the
      perforation at one and 6 mo, respectively. In contrast, 60% (n = 6) of the 10
      ears (8 patients) without initial myringoplasty did not heal spontaneously at 6
      mo, and these ears underwent a delayed tympanoplasty procedure. Notably, patients
      with early myringoplasty suffered lower conductive hearing loss and fewer
      functional signs remotely. Conclusion: Early myringoplasty using a biomembrane
      for blast injury-induced large tympanic perforation is a fast and minimally
      invasive method to achieve earlier tympanic closure and a higher closure rate for
      safe recovery of activity. It can be performed under general anesthesia
      concurrently with surgery for additional body-wide trauma. The deployment of ENT
      surgeons on the battlefield in the French Army has enabled early management of
      these patients.

PMID- 29635524
TI  - Placental defects are involved in most gene mutations that cause embryonic and
      fetal death.

PMID- 29635525
TI  - Effects of isoniazid resistance on TB treatment outcomes under programmatic
      conditions in a high-TB and -HIV setting: a prospective multicentre study
      authors' response.

PMID- 29635526
TI  - Oncological and peri-surgical outcomes of radical prostatectomy for non
      metastatic prostate cancer with prostate-specific antigen level of 50 ng/ml or
      greater.
AB  - Background: The role of radical prostatectomy in treating non-metastatic prostate
      cancer patients with high prostate-specific antigen levels remains unclear. We
      evaluated the feasibility and oncological outcomes of radical prostatectomy in
      non-metastatic prostate cancer patients with prostate-specific antigen levels of
      50 ng/ml or higher. Methods: This retrospective study included 31 patients who
      were diagnosed as very high-risk prostate cancer (clinical stage of any T, N0-1
      M0 and PSA levels >=50 ng/ml) and underwent radical prostatectomy either as a
      monotherapy or as a component of multimodal therapy (RP group). Surgery-related
      complications were investigated. Time to castration-resistant prostate cancer,
      cancer-specific survival, and overall survival were estimated using the Kaplan
      Meier method. A total of 47 patients with very high-risk prostate cancer who were
      treated with androgen deprivation therapy without local therapy served as a
      control group (ADT group). Survivals were compared between RP group and ADT group
      in exploratory analyses. Results: The median pretreatment prostate-specific
      antigen was 87 ng/ml and 100 ng/ml in the RP and ADT groups, respectively (P =
      0.67). Surgical complications of Clavien-Dindo Grade 3 were documented in nine
      patients (29%). Ten-year castration-resistant prostate cancer-free, cancer
      specific and overall survivals were 78%, 81% and 77% in RP group, respectively,
      and they were significantly better than those of ADT group (54%, P = 0.006; 54%,
      P = 0.006 and 38%, P < 0.001). Exploratory multivariate analysis identified
      radical prostatectomy as the only significant factor associated with a better
      cancer-specific survival (hazard ratio: 0.25, P = 0.006). Conclusions: Radical
      prostatectomy is feasible for non-metastatic prostate cancer patients with
      prostate-specific antigen levels of 50 ng/ml or higher. Radical prostatectomy is
      a viable option for select patients with non-metastatic, very high-risk prostate
      cancer.

PMID- 29635527
TI  - Impact of intensification with raltegravir on HIV-1-infected individuals
      receiving monotherapy with boosted PIs.
AB  - Background: Monotherapy with ritonavir-boosted PIs (PI/r) has been used to
      simplify treatment of HIV-1-infected patients. In previous studies raltegravir
      intensification evidenced ongoing viral replication and reduced T cell
      activation, preferentially in subjects receiving PI-based triple ART. However,
      data about low-level viral replication and its consequences in patients receiving
      PI/r monotherapy are scarce. Methods: We evaluated the impact of 24 weeks of
      intensification with raltegravir on markers of viral persistence, cellular immune
      activation and inflammation biomarkers in 33 patients receiving maintenance PI/r
      monotherapy with darunavir or lopinavir boosted with ritonavir.
      ClinicalTrials.gov identifier: NCT01480713. Results: The addition of raltegravir
      to PI/r monotherapy resulted in a transient increase in 2-LTR (long-terminal
      repeat) circles in a significant proportion of participants, along with decreases
      in CD8+ T cell activation levels and a temporary increase in the expression of
      the exhaustion marker CTLA-4 in peripheral T lymphocytes. Intensification with
      raltegravir also reduced the number of samples with intermediate levels of
      residual viraemia (10-60 HIV-1 RNA copies/mL) compared with samples taken during
      PI/r monotherapy. However, there were no changes in cell-associated HIV-1 DNA in
      peripheral CD4+ T cells or soluble inflammatory biomarkers (CD14, IP-10, IL-6, C
      reactive protein and D-dimer). Conclusions: Intensification of PI/r monotherapy
      with raltegravir revealed persistent low-level viral replication and reduced
      residual viraemia in some patients during long-term PI/r monotherapy. The
      concomitant change in T cell phenotype suggests an association between active
      viral production and T cell activation. These results contribute to understanding
      the lower efficacy rates of PI/r monotherapies compared with triple therapies in
      clinical trials.

PMID- 29635528
TI  - Tocilizumab concentrations in maternal serum and breast milk during breastfeeding
      and a safety assessment in infants: a case study.

PMID- 29635529
TI  - Acute Encephalitis Syndrome in Eastern Uttar Pradesh, India: Changing Etiological
      Understanding.
AB  - Seasonal outbreaks of acute encephalitis syndrome (AES) with high case fatality
      have been occurring in Gorakhpur division in Eastern Uttar Pradesh, India, for
      more than three decades. Japanese encephalitis virus (JEV) accounted for <10% of
      AES cases, while the etiology of the remaining cases remained largely unknown.
      Investigations conducted during the 2014 and 2015 outbreaks indicated Orientia
      tsutsugamushi (Haruo Hayashi 1920) (Norio Ogata 1929) Tamura et al. 1995
      (Rickettsiales: Rickettsiaceae) as the etiology in about 60% of AES cases.
      Hospital-based surveillance studies indicated that about one-fifth of the
      patients with acute febrile illness were due to scrub typhus. Further studies are
      required to identify the etiology of about a third of AES cases that test
      negative for scrub typhus, JEV, or dengue.

PMID- 29635530
TI  - The Impact of Stressful Life Events on the Incidence of Type 2 Diabetes in U.S.
      Adults from the Health and Retirement Study.
AB  - Objectives: We evaluated the association between cumulative stressful life events
      (SLE) and type of stress (lifetime vs. recent) and incident diabetes (T2DM) in
      middle-aged U.S. adults. Methods: Data from the 2006-2014 waves of the Health and
      Retirement Study (HRS) were analyzed (n = 7956). Stress-related differences in
      age at T2DM diagnosis were estimated using Cox proportional hazards models.
      Results: The adjusted risk of T2DM significantly increased by six percent per
      unit increase in cumulative SLE (95% CI = 1.03, 1.11), by five percent per unit
      increase in lifetime stress (95% CI = 1.00, 1.09), and by 23% per unit increase
      in recent stress (95% CI = 1.12, 1.36). Each level of cumulative SLE (one, two,
      three, and > four events) and recent stress (one and > two events) compared to no
      stress was significantly associated with an increased risk of T2DM. Each level of
      lifetime stress compared to no stress was significantly associated with an
      elevated risk of T2DM except for three events. Discussion: Cumulative SLE and
      type of stress were associated with incident T2DM in middle-aged adults. Reducing
      the direct effect of stress with management interventions may reduce the indirect
      effect of developing T2DM and warrants further investigation.

PMID- 29635531
TI  - Independent Predictors for Higher Postoperative Pain Intensity During Recovery
      After Open Thoracic Surgery: A Retrospective Analysis in 621 Patients.
AB  - Objective: To evaluate two standard procedure-specific pain regimens and to
      assess independent predictors for higher pain intensity after thoracic surgery.
      Methods: Patients received either oral opioid analgesia (Opioid Group) or
      epidural analgesia and were then bridged to systemic opioid analgesia (EDA + O
      Group) in this retrospective observational study. Medical history, discharge
      letters, anesthetic protocols, and pain protocols were evaluated in 621 patients
      after open thoracotomy and assessed with a stepward back elimination in a
      multivariate logistic regression model. Results: Data of 621 thoracotomies in
      2014 were analyzed, 309 patients in the Opioid Group and 312 patients in the EDA
      + O Group. Pain scores at rest and on coughing were significantly lower in the
      EDA + O Group on postoperative days (PODs) 1-4 (P < 0.001). Stepwise backward
      elimination in multivariate logistic regression identified preexisting pain
      disease (P = 0.034), no epidural analgesia (P < 0.001), opioids in preoperative
      pain therapy (P < 0.001), and antidepressant medication (P = 0.003) as
      independent risk factors for higher pain intensity at rest on PODs 1-4. Same on
      PODs 5-8 with regard to opioids in preoperative pain therapy (P < 0.001) and
      antidepressant medication (P = 0.018). Moreover, on PODs 5-8, male gender had a
      lower risk (P < 0.003) for pain, and preexisting musculosceletal disease had a
      lower risk for more postoperative pain (P = 0.009). On coughing, male gender and
      younger age proved to have a lower risk for postoperative pain on PODs 1-8 and on
      PODs 1-4, respectively. Opioids in preexisting pain therapy and antidepressant
      medication were identified as risk factors for pain on PODs 1-8 on coughing, and
      pain disease was identified as a risk factor for more pain on PODs 1-4 (P =
      0.041). Moreover, preexisting cardiac disease indicated more pain on PODs 1-4 (P
      = 0.05), and musculoskeletal disease and neurological disease indicated more pain
      on PODs 5-8 (P = 0.041, and P = 0.023). Conclusions: We present data on
      independent risk factors for higher pain intensity during recovery after
      thoracotomy. The lack of postoperative epidural analgesia, female gender,
      preexisting opioid pain therapy, and chronic pain are the strongest risk factors
      for higher pain intensity. Antidepressant medication was identified as an
      independent risk factor at rest and on coughing on all PODs. Study limitations:
      The study design is retrospective.

PMID- 29635532
TI  - Transmural circumflex infarction in a young Fontan patient: to leave home to find
      it.

PMID- 29635533
TI  - Effect of Military Deployment on Diabetes Mellitus in Air Force Personnel.
AB  - Introduction: Military deployments relocate service members to austere locations
      with limited medical capabilities, raising uncertainties whether members with
      diabetes can participate safely. Military regulations require a medical clearance
      for service members with diabetes prior to deployment, but there is a dearth of
      data that can guide the provider in this decision. To alleviate the lack of
      evidence in this area, we analyzed the change in glycated hemoglobin (HbA1c) and
      body mass index (BMI) before and after a deployment among active duty U.S. Air
      Force personnel who deployed with diabetes. Materials and Methods: A
      retrospective analysis was conducted using HbA1c and BMI values obtained within 3
      mo before and within 3 mo after repatriation from a deployment of at least 90 d
      between January 1, 2004 through December 31, 2014. The study population consisted
      of 103 and 195 subjects who had an available pre- and post-deployment HbA1c and
      BMI values, respectively. Paired t-tests were conducted to determine significant
      differences in HbA1C and BMI values. Results: The majority (73.8%) of members had
      a HbA1c <7.0% (53 mmol/mol) prior to deployment. For the overall population,
      HbA1c before and after deployment decreased from 6.7% (50 mmol/mol) to 6.5% (40
      mmol/mol) (p = 0.03). Subgroup analysis demonstrated a significant decline in
      HbA1c among males, those aged 31-40 yr, and those with a pre-deployment HbA1c of
      >7%. BMI declined for the overall population (28.3 kg/m2 vs. 27.7 kg/m2, p <
      0.0001) and for most of the subgroups. Conclusion: Air Force service members who
      deployed with diabetes, including those with a HbA1c > 7%, experienced a
      statistically significant improvement in HbA1c and BMI upon repatriation. A
      prospective study design in the future can better reconcile the effect of a
      military deployment on a more comprehensive array of diabetes parameters.

PMID- 29635534
TI  - Efficacy of heparinoid moisturizer as a prophylactic agent for radiation
      dermatitis following radiotherapy after breast-conserving surgery: a randomized
      controlled trial.
AB  - Background: The application of heparinoid moisturizer for 2 weeks following whole
      breast radiotherapy (WBRT) was previously reported to significantly increase skin
      water content (WC) and help improve skin dryness and desquamation. The
      prospective open-label, randomized trial included an exploratory arm to
      investigate the preventive efficacy of heparinoid moisturizer for acute radiation
      dermatitis (ARD). Methods: Between April 2011 and April 2013, patients receiving
      WBRT were assigned (1:2:2) to receive either: moisturizer for prophylaxis (group
      P), moisturizer starting 2 weeks after WBRT for treatment (group M), and no
      moisturizer (group C). This paper presents the results of comparison between the
      exploratory arm and no moisturizer group. Skin WC was measured prior to WBRT, on
      the last day of WBRT, and 2 weeks, 4 weeks and 3 months following WBRT. Signs and
      symptoms were also assessed. Results: Comparing two groups, WC values were
      significantly higher in group P until 4 weeks following WBRT. At 2 weeks
      following WBRT, mean WC values in group P and C were 38.5 +/- 6.1 arbitrary units
      (a.u.) and 30.2 +/- 7.8 a.u., respectively (P < 0.001). In group C, dryness was
      more severe at 2 and 4 weeks following WBRT and desquamation more severe until 3
      months following WBRT. However, the erythema score showed no difference between
      the two groups. Regarding symptoms, group C pain scores on the last day of WBRT
      were significantly higher than in group P (P < 0.030). Conclusions: The
      preventive application of heparinoid moisturizer has the potential of reducing
      skin desquamation and dryness in patients receiving WBRT.

PMID- 29635535
TI  - Defective gene expression of the membrane complement inhibitor CD46 in patients
      with progressive immunoglobulin A nephropathy.
AB  - Background: Complement is thought to play a role in immunoglobulin A nephropathy
      (IgAN), though the activating mechanisms are unknown. This study focused on the
      gene expression of CD46 and CD55, two key molecules for regulating C3 convertase
      activity of lectin and alternative complement pathways at a cellular level.
      Methods: The transcriptional expression in peripheral white blood cells (WBCs) of
      CD46 and CD55 was investigated in 157 patients enrolled by the Validation of the
      Oxford Classification of IgAN group, looking for correlations with clinical and
      pathology features and estimated glomerular filtration rate (eGFR) modifications
      from renal biopsy to sampling. Patients had a previous median follow-up of 6.4
      (interquartile range 2.8-10.7) years and were divided into progressors and non
      progressors according to the median value of their velocity of loss of renal
      function per year (-0.41 mL/min/1.73 m2/year). Results: CD46 and CD55 messenger
      RNA (mRNA) expression in WBCs was not correlated with eGFR values or proteinuria
      at sampling. CD46 mRNA was significantly correlated with eGFR decline rate as a
      continuous outcome variable (P = 0.014). A significant difference was found in
      CD46 gene expression between progressors and non-progressors (P = 0.013). CD46
      and CD55 mRNA levels were significantly correlated (P < 0.01), although no
      difference between progressors and non-progressors was found for CD55 mRNA
      values. The prediction of progression was increased when CD46 and CD55 mRNA
      expressions were added to clinical data at renal biopsy (eGFR, proteinuria and
      mean arterial blood pressure) and Oxford MEST-C (mesangial hypercellularity,
      endocapillary hypercellularity, segmental glomerulosclerosis, tubular
      atrophy/interstitial fibrosis, presence of any crescents) score. Conclusions:
      Patients with progressive IgAN showed lower expression of mRNA encoding for the
      complement inhibitory protein CD46, which may implicate a defective regulation of
      C3 convertase with uncontrolled complement activation.

PMID- 29635536
TI  - Stereotactic body radiotherapy (SBRT) for Stage I lung cancer.
AB  - Stereotactic body radiation therapy (SBRT) is a newly developed technique
      currently in clinical use. SBRT originated from stereotactic radiosurgery (SRS)
      for intracranial tumors. Since the 1990s, SBRT has been widely used in clinical
      settings for the treatment of lung cancer. We review the history and current
      standard techniques. Previous clinical studies of lung cancer showed high local
      control rates with acceptable toxicities. Past and on-going clinical trials are
      also reviewed.

PMID- 29635537
TI  - Revision of the medically relevant species of the yeast genus Diutina.
AB  - Diutina (Candida) rugosa is emerging as a causative agent of human infections.
      Recently some close relatives have been described, that is, D. mesorugosa, D.
      pseudorugosa, and D. neorugosa, some of which have also been implicated in human
      infection. Phylogenetic relationships of 24 clinical isolates of the D. rugosa
      complex are reconstructed using multilocus sequence analysis of five housekeeping
      genes, supplemented with phenotypic studies of CandiSelectTM 4 Agar and
      nutritional physiology. Diutina mesorugosa could not meaningfully be
      distinguished from D. rugosa and is regarded as a synonym. Diutina neorugosa and
      D. pseudorugosa represent separate, distantly related species within the genus
      Diutina, but have as yet not been encountered in clinical settings.

PMID- 29635538
TI  - Genome Re-Sequencing of Diverse Sweet Cherry (Prunus avium) Individuals Reveals a
      Modifier Gene Mutation Conferring Pollen-Part Self-Compatibility.
AB  - The S-RNase-based gametophytic self-incompatibility (GSI) reproduction barrier is
      important for maintaining genetic diversity in species of the families
      Solanaceae, Plantaginaceae and Rosaceae. Among the plant taxa with S-RNase-based
      GSI, Prunus species in the family Rosaceae exhibit Prunus-specific self
      incompatibility (SI). Although pistil S and pollen S determinants have been
      identified, the mechanism underlying SI remains uncharacterized in Prunus
      species. A putative pollen-part modifier was identified in this study. Disruption
      of this modifier supposedly confers self-compatibility (SC) to sweet cherry
      (Prunus avium) 'Cristobalina'. To identify the modifier, genome re-sequencing
      experiments were completed involving sweet cherry individuals from 18 cultivars
      and 43 individuals in two segregating populations. Cataloging of subsequences (35
      bp kmers) from the obtained genomic reads, while referring to the mRNA sequencing
      data, enabled the identification of a candidate gene [M locus-encoded GST
      (MGST)]. Additionally, the insertion of a transposon-like sequence in the
      putative MGST promoter region in 'Cristobalina' down-regulated MGST expression
      levels, probably leading to the SC of this cultivar. Phylogenetic, evolutionary
      and gene expression analyses revealed that MGST may have undergone lineage
      specific evolution, and the encoded protein may function differently from the
      corresponding proteins encoded by GST orthologs in other species, including
      members of the subfamily Maloideae (Rosaceae). Thus, MGST may be important for
      Prunus-specific SI. The identification of this novel modifier will expand our
      understanding of the Prunus-specific GSI system. We herein discuss the possible
      functions of MGST in the Prunus-specific GSI system.

PMID- 29635539
TI  - The Initial Impact of Tele-Critical Care on the Surgical Services of a Community
      Military Hospital.
AB  - Introduction: Mortality is reduced in hospitals staffed with intensivists,
      however, many smaller military hospitals lack intensivist support. Naval Hospital
      Camp Pendleton (NHCP) is a Military Treatment Facility (MTF) that operates a 6
      bed Intensive Care Unit (ICU) north of its referral center, Naval Medical Center
      San Diego (NMCSD). To address a gap in NHCP on-site intensivist coverage, a
      comprehensive Tele-Critical Care (TCC) support system was established between
      NHCP and NMCSD. To examine the initial impact of telemedicine on surgical ICU
      patients, we compare NHCP surgical ICU admissions before and after TCC
      implementation. Materials and methods: Patient care by remote intensivist was
      achieved utilizing video teleconferencing technology, and remote access to
      electronic medical records. Standardization was promoted by adopting protocols
      and mandatory intensivist involvement in all ICU admissions. Surgical ICU
      admissions prior to TCC implementation (pre-TCC) were compared to those following
      TCC implementation (post-TCC). Results: Of 828 ICU admissions, 21% were surgical.
      TCC provided coverage during 35% of the intervention period. Comparing pre-TCC
      and post-TCC periods, there was a significant increase in the percentage of
      surgical ICU admissions [15.3 % vs 24.6%, p = 0.01] and the average monthly
      APACHE II score [4.1vs 6.5, p = 0.03]. The total number of surgical admissions
      per month also increased [3.9 vs 6.3, p = 0.009]. No adverse outcomes were
      identified. Conclusion: Implementation of TCC was associated with an increase in
      the scope and complexity of surgical admissions with no adverse outcomes.
      Surgeons were able to safely expand the surgical services offered requiring
      perioperative ICU care to patients who previously may have been transferred.
      Caring for these types of patients not only maintains the operational readiness
      of deployable caregivers but patient experience is also enhanced by minimizing
      transfers away from family. Further exploration of TCC on surgical case volume
      and complexity is warranted.

PMID- 29635541
TI  - Jumpstarting Monitoring and Evaluation for Global Health Engagement.

PMID- 29635540
TI  - A Framework for Resolving Cryptic Species: A Case Study from the Lizards of the
      Australian Wet Tropics.
AB  - As we collect range-wide genetic data for morphologically-defined species, we
      increasingly unearth evidence for cryptic diversity. Delimiting this cryptic
      diversity is challenging, both because the divergences span a continuum and
      because the lack of overt morphological differentiation suggests divergence has
      proceeded heterogeneously. Herein, we address these challenges as we diagnose and
      describe species in three co-occurring species groups of Australian lizards. By
      integrating genomic and morphological data with data on hybridization and
      introgression from contact zones, we explore several approaches-and their
      relative benefits and weaknesses-for testing the validity of cryptic lineages.
      More generally, we advocate that genetic delimitations of cryptic diversity must
      consider whether these lineages are likely to be durable and persistent through
      evolutionary time.

PMID- 29635542
TI  - Targeted methylation sequencing of plasma cell-free DNA for cancer detection and
      classification.
AB  - Background: Targeted methylation sequencing of plasma cell-free DNA (cfDNA) has a
      potential to expand liquid biopsies to patients with tumors without detectable
      oncogenic alterations, which can be potentially useful in early diagnosis.
      Patients and methods: We developed a comprehensive methylation sequencing assay
      targeting 9223 CpG sites consistently hypermethylated according to The Cancer
      Genome Atlas. Next, we carried out a clinical validation of our method using
      plasma cfDNA samples from 78 patients with advanced colorectal cancer, non-small
      cell lung cancer (NSCLC), breast cancer or melanoma and compared results with
      patients' outcomes. Results: Median methylation scores in plasma cfDNA samples
      from patients on therapy were lower than from patients off therapy (4.74 versus
      85.29; P = 0.001). Of 68 plasma samples from patients off therapy, methylation
      scores detected the presence of cancer in 57 (83.8%), and methylation-based
      signatures accurately classified the underlying cancer type in 45 (78.9%) of
      these. Methylation scores were most accurate in detecting colorectal cancer
      (96.3%), followed by breast cancer (91.7%), melanoma (81.8%) and NSCLC (61.1%),
      and most accurate in classifying the underlying cancer type in colorectal cancer
      (88.5%), followed by NSCLC (81.8%), breast cancer (72.7%) and melanoma (55.6%).
      Low methylation scores versus high were associated with longer survival (10.4
      versus 4.4 months, P < 0.001) and longer time-to-treatment failure (2.8 versus
      1.6 months, P = 0.016). Conclusions: Comprehensive targeted methylation
      sequencing of 9223 CpG sites in plasma cfDNA from patients with common advanced
      cancers detects the presence of cancer and underlying cancer type with high
      accuracy. Methylation scores in plasma cfDNA correspond with treatment outcomes.

PMID- 29635543
TI  - Processing diets containing corn distillers' dried grains with solubles in
      growing broiler chickens: effects on performance, pellet quality, ileal amino
      acids digestibility, and intestinal microbiota.
AB  - The present study investigated the effects of feed form and distillers' dried
      grains with solubles (DDGS) on growth performance, nutrient digestibility, and
      intestine microbiota in broilers. A total of 720 broilers (Ross 308; average BW
      541 +/- 6 g) was randomly allotted to 6 treatments on the basis of BW. There were
      6 replicates in each treatment with 20 birds per replicate. Birds were fed 3
      different feed forms (mash, simple pellet, and expanded pellet) and DDGS (0 or
      20% of diet) in a 3 * 2 factorial arrangement. Simple pellet (SP) and expanded
      pellet (EP) fed birds showed an increase in BW gain (P < 0.05). The interaction
      between feed processing and DDGS level was observed on pellet hardness (P <
      0.01). The lowest (P < 0.01) pellet durability index (PDI) and hardness were
      observed in the diet with DDGS. Values for PDI and hardness were higher for EP
      compared with SP (P < 0.01). Simple pellet decreased ileal digestibility of CP
      compared to mash feed. The inclusion of DDGS decreased the digestibility of CP,
      and tended to decrease digestibility of DM (P = 0.056) and gross energy (P =
      0.069). Expanded pellet feeding decreased (P < 0.05) the ileal digestibility of
      isoleucine, lysine, methionine, phenylalanine, threonine, cysteine, and glutamine
      compared with mash diet. Processed feed increased (P < 0.01) pH in the gizzard
      and duodenum; however, processing decreased pH in ileum. The addition of DDGS to
      the diet reduced pH in the duodenum. The population of Lactobacillus spp. was
      lower in the duodenum of birds fed the EP diet compared to the mash diet.
      Processed feed increased the colonization of Clostridium spp. in the gizzard.
      These results indicated that SP and EP in broiler diet had a potential to improve
      BW gain, but EP compromised amino acid digestibility. In addition, DDGS
      supplementation (20%) decreased pellet quality and CP digestibility in broiler
      chickens; however, the growth performance and feed intake were not affected.

PMID- 29635545
TI  - Influenza in Transplant Recipients: Many Outstanding Questions Despite a Growing
      Body of Data.

PMID- 29635544
TI  - Hypovolemia due to cerebral salt wasting may contribute to stroke in tuberculous
      meningitis.
AB  - Background: Both stroke and cerebral salt wasting (CSW) are common in tuberculous
      meningitis (TBM), but there is paucity of studies evaluating their combined
      effect. Aim: The present study has been undertaken to evaluate the spectrum of
      stroke in TBM and its relation to CSW. Design: Hospital-based prospective cohort
      study. Methods: Eighty-one patients with TBM diagnosed on the basis of clinical,
      cerebrospinal fluid and magnetic resonance imaging (MRI) criteria were
      prospectively included. Stroke was diagnosed on the basis of clinical, MRI
      findings or both. Stroke risk factors were noted. Patients with hyponatremia were
      categorized into CSW and other causes. Three and 6 months outcome was defined
      using modified Rankin Scale (mRS) as good (<2) or poor (>=2). Results: Out of 81
      patients with TBM, 32 (39.5%) had ischemic stroke. CSW was the commonest cause of
      hyponatremia and occurred in 34 (42%) patients. Stroke occurred in tubercular
      zone in 10, ischemic zone in 15 and both in 7 patients. The patients with
      ischemic zone infarction were older and had stroke risk factors such as diabetes
      mellitus, hypertension and hyperlipidemia. Out of 16 (47%) patients with CSW, 10
      (62.5%) had stroke during the polyuric phase. The patients with CSW had more
      frequent deep white matter infarcts (P = 0.01) which were in internal border zone
      in 4 (40%). Conclusion: In TBM, stroke occurred in 39.5% of the patients, 50% of
      whom had CSW. Volume contraction due to CSW may contribute to stroke.

PMID- 29635546
TI  - Non-disclosure of symptoms in primary care: an observational study.
AB  - Background: Symptoms form a major component of patient agendas, with the need for
      an explanation of symptoms being a prominent reason for consultation. Objectives:
      To estimate the prevalence of different symptoms pre-consultation, to investigate
      whether intention to mention a symptom in the consultation varied between
      patients and across symptoms, and to determine how patients' intended agendas for
      mentioning symptoms compared with what was discussed. Method: We videorecorded
      consultations of an unselected sample of people aged 45 and over consulting their
      GP in seven different practices in UK primary care. A pre-consultation
      questionnaire recorded the patient's agenda for the consultation, current
      symptoms and symptoms the patient intended to discuss with their GP. The
      videorecorded consultation was viewed and all patient agendas and 'symptoms with
      intention to discuss' were compared with the actual topics of discussion.
      Results: Totally, 190 patients participated. Eighty-one (42.6%) were female and
      the mean age was 68 (range 46-93). Joint pain was the most commonly reported
      symptom. One hundred thirty-nine (81.8% of those reporting symptoms) patients
      reported intention to discuss a symptom. In 43 (22.6%) consultations, 67 symptoms
      (27.2%), where an intention to discuss had been expressed, remained undisclosed.
      Tiredness and sleeping difficulty were more likely to be withheld than other
      symptoms after an intention to discuss had been expressed. Of the more physically
      located symptoms, joint pain was the most likely to remain undisclosed.
      Conclusion: This study suggests that the extent of symptom non-disclosure varies
      between patients, physicians and symptoms. Further work needs to explore the
      consequences of non-disclosure.

PMID- 29635547
TI  - Continuous Veno-Venous Hemofiltration During Intercontinental Aeromedical
      Evacuation.
AB  - Overseas contingency operations which occur in areas lacking medical
      infrastructure pose challenges to the stabilization and transportation of
      critically ill patients. In particular, metabolic derangements resulting from
      acute kidney injury (AKI) make long-distance aeromedical evacuation risky. Here,
      we report the first modern use of in-flight continuous veno-venous hemofiltration
      (CVVH) for intercontinental aeromedical evacuation. Hospital and transport
      records were reviewed for a 31-yr-old male active duty service member who
      sustained 40% total body surface area full thickness burns after high-voltage
      electrical exposure in the southern Philippines. He was evacuated to the Burns
      Centre at Singapore General Hospital, where CVVH was initiated for anuric AKI
      secondary to rhabdomyolysis. The United States Army Institute of Surgical
      Research (USAISR) Burn Flight Team transported the patient to the USAISR Burn
      Center at Fort Sam Houston, TX, USA. CVVH was performed in-flight for 15 h out of
      19.5 h of total flight time. CVVH settings were maintained as follows: blood flow
      250 mL/min; replacement fluid rate 3,500 mL/h; and no ultra-filtrate removal.
      Unfractionated heparin at 500 units/h was utilized for regional anticoagulation.
      No filter clotting was encountered; a planned filter change was performed during
      a midway refueling stop. Pre-flight hyperkalemia was managed with low-potassium
      replacement fluid. No fluid was removed in the setting of large wound insensible
      losses. The patient remained hemodynamically stable and required no vasoactive
      medications. Continuous veno-venous hemofiltration can be used safely during high
      altitude flight to evacuate casualties with AKI from distant contingency
      operations. The use of portable hemodialysis equipment in this case also proves
      the feasibility of deploying renal replacement therapies to more forward
      facilities than previously considered.

PMID- 29635548
TI  - A Novel Peptide-Based Antimicrobial Wound Treatment is Effective Against Biofilms
      of Multi-Drug Resistant Wound Pathogens.
AB  - Wound infections are a common complication of combat-related injuries that
      significantly increase morbidity and mortality. Multi-drug resistant (MDR)
      organisms and their associated biofilms play a significant role in the
      pathogenicity and chronicity of wound infections. A critical barrier to progress
      in the treatment of traumatic wounds is the need for broad spectrum
      antimicrobials that are effective against biofilms and compatible with topical
      delivery. In this study, we present the in vitro efficacy of two de novo designed
      cationic, antimicrobial peptides and related topical formulations against single
      species and polymicrobial biofilms of MDR bacteria. Minimum biofilm eradication
      concentrations for peptides ranged from 0.7 MUM for Staphylococcus aureus to 13.2
      MUM for Pseudomonas aeruginosa. Varying pH did not adversely impact peptide
      activity, however, in the presence of albumin, minimum biofilm eradication
      concentrations generally increased. When formulated into gels or dressings, both
      peptides eradicated mono- and polymicrobial biofilms of MDR pathogens. The
      biocompatibility index (BI) was found to be greater than one for both ASP-1 and
      ASP-2, with a slightly greater (more favorable) BI for ASP-2. The BIs for both
      peptides were greater than BIs previously reported for commonly used topical
      antimicrobial agents. The antimicrobial peptides and related formulations
      presented provide a promising platform for treatment of wound biofilms to improve
      outcomes for those injured in combat.

PMID- 29635549
TI  - Perceptions of Simulator- and Live Tissue-Based Combat Casualty Care Training of
      Senior Special Operations Medics.
AB  - The relative effectiveness of live tissue (LT)- and inanimate simulation (SIM)
      based training of combat medics is the subject of intense debate. A structured
      interview was utilized to determine the training modality preferences and the
      perceived value of LT- and SIM-based combat casualty care training of 25 senior
      special operations medics. Participant demographics and training experience,
      Likert scale-based assessment of training modality value, selection of preferred
      training modality for 11 combat casualty care procedures, and 12 open-ended
      questions probing opinions of the limitations and benefits of LT- and SIM-based
      training were collected from this convenience sample. All participants indicated
      significant combat medic experience and training. Of the 11 procedures
      questioned, LT was identified as superior for seven with mixed responses for the
      remaining four. LT was consistently identified as an essential training modality
      with tactile sensation and the physiologic responses of animal models to injury
      and therapy as primary benefits. Across procedures, 100% of participants felt
      that LT should be used in combat casualty care training and 96% felt that SIM
      should also be utilized. Repeatability and accuracy of size/weight were
      identified as key benefits of SIM training. Respondents reported that capability,
      self-confidence, success, and resilience of the combat medic all benefitted from
      LT training. The overriding theme was the general superiority of LT with
      recognition of the unique and complementary benefits of SIM.

PMID- 29635550
TI  - Utilizing Propensity Score Analyses in Prehospital Blood Product Transfusion
      Studies: Lessons Learned and Moving Toward Best Practice.
AB  - Recently, observational studies analyzing prehospital blood product transfusions
      (PHT) for trauma have become more widespread in both military and civilian
      communities. Due to these studies' non-random treatment assignment, propensity
      score (PS) methodologies are often used to determine an intervention's
      effectiveness. However, there are no guidelines on how to appropriately conduct
      PS analyses in prehospital studies. Such analyses are complicated when treatments
      are given in emergent settings as the ability to administer treatment early,
      often before hospital admission, can interfere with assumptions of PS modeling.
      This study conducts a systematic review of literature from military and civilian
      populations to assess current practice of PS methodology in PHT analyses. The
      decision-making process from the multicenter Prehospital Resuscitation on
      Helicopter Study (PROHS) is discussed and used as a motivating example. Results
      show that researchers often omit or incorrectly assess variable balance between
      treatment groups and include inappropriate variables in the propensity model.
      When used correctly, PS methodology is an effective statistical technique to show
      that aggressive en route resuscitation strategies, including PHT, can reduce
      mortality in individuals with severe trauma. This review provides guidelines for
      best practices in study design and analyses that will advance trauma care.

PMID- 29635551
TI  - Virtual Reality Training System for Anytime/Anywhere Acquisition of Surgical
      Skills: A Pilot Study.
AB  - This article presents a hardware/software simulation environment suitable for
      anytime/anywhere surgical skills training. It blends the advantages of physical
      hardware and task analogs with the flexibility of virtual environments. This is
      further enhanced by a web-based implementation of training feedback accessible to
      both trainees and trainers. Our training system provides a self-paced and
      interactive means to attain proficiency in basic tasks that could potentially be
      applied across a spectrum of trainees from first responder field medical
      personnel to physicians. This results in a powerful training tool for surgical
      skills acquisition relevant to helping injured warfighters.

PMID- 29635552
TI  - Modeling and Comparing Nurse and Physician Trauma Assessment Skills.
AB  - Medical providers must master a large number of complicated tasks to deliver
      quality care and minimize unwanted clinical outcomes. In order to optimally train
      these tasks, medical training systems would benefit from models of skill that
      enable objective assessment of proficiency and define important declarative
      knowledge, cognitive states, and decision-making rules that are necessary for
      effective learning and performance. This article describes the Methodology for
      Annotated Skill Trees (MAST), a skill-modeling framework that facilitates the
      creation of descriptive and rule-based content that supports skill acquisition.
      This framework is used to generate models of trauma assessment skills from two
      existing curricula: Advanced Trauma Life Support (ATLS) and the Trauma Nurse Core
      Course (TNCC). Key differences between these curricula's teaching methods for the
      same procedure and skill are highlighted through the use of the model framework.
      The framework comparison provides insight into the underlying teaching approach
      and highlights the fact that some skills are not represented in medical education
      materials.

PMID- 29635553
TI  - Simulation Training for Operational Medicine Providers (STOMP): Design and
      Implementation of a Novel Comprehensive Skills-Based Curriculum for Military
      General Medical Officers.
AB  - Background: Fifty percent of graduating U.S. Navy post-graduate year (PGY)-1
      physicians will practice in the operational environment before returning to
      residency training. However, current internship structure is less rotational and
      focuses more on specialty-specific training. Therefore, these physicians may not
      be fully prepared for this primary care role. Methods: Based on the U.S. Navy
      privileges for General Medical Officers, a comprehensive didactic and simulation
      curriculum was developed. Twenty-three procedural skill competencies (SK) and
      five validated standardized patient (SP) scenarios were identified. During the SK
      portion, learners reviewed instructional videos, read reference materials, and
      practiced with partial task trainers before small-group sessions with subject
      matter experts (SME). Separate SP round-robin sessions were conducted and
      feedback provided by SMEs and SPs. Learners demonstrated competency or were
      remediated. Results: One hundred and three PGY-1 trainees participated over 2 yr.
      All trainees met requirements during the SK phase. During the SP phase, seven
      learners required remediation. All learners ultimately met requirements for
      privileging. Conclusion: The Simulation Training for Operational Medicine
      Providers curriculum for future General Medical Officers is an effective tool for
      primary care skill training and credentialing. Plans for export to other Graduate
      Medical Education sites are underway and further evaluation of skills retention
      is warranted.

PMID- 29635554
TI  - Videoconferenced Telebehavioral Health Referral Process Adherence.
AB  - Background: In 2015, the Army mandated 100% digital storage of telehealth consent
      forms (DA4700) in the Health Artifact and Image Management Solution (HAIMS)
      system, and a telebehavioral health (TBH) hub clinic set an aim to accomplish
      this by improving adherence to referral procedures essential to expanding patient
      access to videoconferenced (VC) behavioral health care. Methods: The Knowledge-to
      Action (KTA) planned action framework underpinned development of a two-phase,
      PDSA (Plan-Do-Study-Act) quality improvement project to increase the rates of TBH
      new intake consent form completeness and upload adherence. First, a provider
      education initiative addressed form uploads. Second, TBH consultants prepared
      (signed and sent) intake forms to referring sites for their patients to finalize
      during the initial VC encounter. A chart review of consecutive new intake
      encounters compared data extracted from CY2015 Q1 baseline records (n = 65) with
      data from CY2016 Q1 improvement period records (n = 40). A total of 352 forms
      were reviewed. Results: Referrals (N = 118) that resulted in kept new VC TBH
      intake visits (n = 105), originated from three military behavioral health clinic
      referral sites. In CY2016 Q1, all DA4700 consent forms were uploaded to HAIMS.
      Telehealth treatment and medication consent form upload adherence increased from
      94% and 68%, respectively, to 100% (p > 0.05). Form completeness increased from
      36% to 95% (p < 0.001), and multiple linear regression analysis predicted an
      average 59% increase across the three referral sites (sr2 = 0.54). Conclusion:
      Consultant preparation of telehealth new intake consent forms effectively
      improved form completeness and increased adherence to new intake referral
      processes essential to this hub clinic expanding patient access to TBH care.

PMID- 29635555
TI  - Using 3D Printing (Additive Manufacturing) to Produce Low-Cost Simulation Models
      for Medical Training.
AB  - Objectives: This work describes customized, task-specific simulation models
      derived from 3D printing in clinical settings and medical professional training
      programs. Methods: Simulation models/task trainers have an array of purposes and
      desired achievements for the trainee, defining that these are the first step in
      the production process. After this purpose is defined, computer-aided design and
      3D printing (additive manufacturing) are used to create a customized anatomical
      model. Simulation models then undergo initial in-house testing by medical
      specialists followed by a larger scale beta testing. Feedback is acquired, via
      surveys, to validate effectiveness and to guide or determine if any future
      modifications and/or improvements are necessary. Results: Numerous custom
      simulation models have been successfully completed with resulting task trainers
      designed for procedures, including removal of ocular foreign bodies, ultrasound
      guided joint injections, nerve block injections, and various suturing and
      reconstruction procedures. These task trainers have been frequently utilized in
      the delivery of simulation-based training with increasing demand. Conclusions: 3D
      printing has been integral to the production of limited-quantity, low-cost
      simulation models across a variety of medical specialties. In general, production
      cost is a small fraction of a commercial, generic simulation model, if available.
      These simulation and training models are customized to the educational need and
      serve an integral role in the education of our military health professionals.

PMID- 29635556
TI  - HIV PrEP in the Military: Experience at a Tertiary Care Military Medical Center.
AB  - Objectives: We evaluated human immunodeficiency virus (HIV) pre-exposure
      prophylaxis (PrEP) administration at the Walter Reed National Military Medical
      Center (WRNMMC), which serves a geographic area at high risk of HIV infection.
      Methods: Medical records were reviewed for all patients initiating PrEP at WRNMMC
      from November 1, 2013, to March 30, 2016. Demographic, laboratory, clinical, and
      risk exposure characteristics and outcomes were described. Results: One hundred
      fifty-nine patients received PrEP; 133 (84%) patients were active duty, 95 (60%)
      patients were over 28 yr old. The majority were non-Hispanic Whites (n = 87,
      55%). The median men who have sex with men (MSM) risk index score was 18.0 (IQR
      12.0-22.0); 20 patients scored less than 10. One hundred and thirty-one (82%)
      patients remained on PrEP through the evaluation period. Patients mainly
      discontinued PrEP for service-related or toxicity reasons. Incident STIs occurred
      in 31 (19%) patients. No cases of HIV seroconversion were observed. Conclusions:
      In this first description of PrEP utilization in a U.S. military health care
      system, a significant number of patients were non-Hispanic Whites, well-educated,
      were older, or were otherwise at low risk for HIV acquisition. Further effort is
      needed to enhance PrEP use among the higher risk young African-American MSM
      population, and further studies are needed to determine the cost-effectiveness of
      PrEP in individuals who are not categorized as high risk.

PMID- 29635557
TI  - Antibiotic Treatment - What Can Be Learned from Point of Injury Experience?
AB  - Introduction: Early antibiotic administration after trauma reduces infection
      rates of open wounds. A clinical practice guideline (CPG) was created to ensure
      that wounded personnel who are not expected to arrive at the hospital within an
      hour receive antibiotic treatment in the field. This study evaluated how well
      advanced life saver (ALS) providers complied with Israeli Defense Force (IDF)
      CPG. Materials and Methods: A retrospective review of all trauma patients between
      November 2011 and January 2015 was conducted. All casualties who suffered from
      penetrating injuries with evacuation times greater than 60 min were examined.
      Casualties who should have received antibiotic treatment in accordance with the
      IDF CPG were further divided into those who received antibiotics (i.e.,
      "Antibiotic" group) and those who did not receive antibiotic treatment (i.e., "No
      Antibiotics" group). Results: For a 3-yr period, a total of 5,142 casualties
      occurred in the pre-hospital environment. According to parameters established in
      the CPG, 600 casualties should have received antibiotic treatment. Of these
      patients, only 49 (8.2%) received antibiotic treatment. Comparative analysis
      between these groups revealed no significant differences in regards to gender,
      age, and time to MTF; however, significant differences were found in regards to
      injury severity score (ISS) (p < 0.01), care under fire (i.e., treatment at a
      combat zone) criteria (p < 0.00001), and life-saving interventions (p < 0.005).
      Discussion: Although the reasons for poor adherence to IDF CPG's are not entirely
      clear, the data suggest that the severity of the injuries sustained by these
      casualties requiring a greater number of LSIs, longer evacuation distances, and a
      more hostile battlefield environment may each contribute to poor adherence. Since
      this has been identified as a training gap, the importance of antibiotic
      administration at point of injury in delayed evacuation scenarios has been
      reinforced.

PMID- 29635558
TI  - Autofluorescence Imaging for Evaluating Debridement in Military and Trauma
      Wounds.
AB  - Background: Mechanisms for military injury have evolved in the past century.
      Debridement is the gold standard for preparing a clean wound bed, decreasing the
      bacterial load, and reducing the likelihood of infection. However, bacteria may
      continue to linger in these wounds. The MolecuLight i:X Imaging Device uses the
      principle of autofluorescence to detect bacteria under violet light. Thus,
      visualizing bacteria will not only guide clinicians in their management of the
      wound but it will also serve as a means of evaluating debridement efforts. We
      hope to improve traumatic wound management by targeting debridement and assessing
      its quality. Methods: We describe the use of the MolecuLight i:X to photograph
      wounds under standard and violet light in three patients. Images were captured
      before and after debridement. Microbiology swabs were collected to correlate the
      bacteria found in the images to the wounds. Results: The post-debridement images
      demonstrate a marked decrease or complete removal of bacteria. The microbiology
      swabs confirmed the pre-debridement presence of bacteria. Conclusions: The
      MolecuLight i:X shows promise for debridement evaluation. The use of the
      MolecuLight i:X may reduce the likelihood of infection, thus having positive
      implications for military and trauma wounds.

PMID- 29635560
TI  - Chronic Neurological Morbidities and Elevated Hippocampal Calcium Levels in a DFP
      Based Rat Model of Gulf War Illness.
AB  - Over 20 yr have elapsed since the end of the First Gulf War, yet approximately
      one-third of the veterans exhibit Gulf War Illness (GWI) symptoms, particularly
      depression and memory impairments. Exposure to organophosphate (OP) compounds is
      implicated for GWI development. The role of calcium (Ca2+) signaling in learning,
      memory, and mood is well established and disruptions in Ca2+ homeostasis are
      observed in many neurological disorders. However, the status of Ca2+ homeostasis
      in the development of GWI behavioral impairments is not known. Male Sprague
      Dawley rats were exposed to OP agent diisopropyl fluorophosphate (DFP; 0.5 mg/kg,
      s.c. 5 days), and at 6 mo post-DFP exposure, rats were subjected to behavioral
      assays for the determination of GWI neurological morbidities. Fura-2AM loaded
      acutely isolated hippocampal neurons were used for [Ca2+]i estimations. We
      observed chronic depressive symptoms and cognitive deficits in rats exposed to
      repeated low-dose DFP. The GWI rats also manifested elevations in hippocampal
      [Ca2+]i along with a significant increase in the number of neurons displaying
      these elevations. As Ca2+ is a major second-messenger molecule, such sustained
      increases in its levels could activate multiple signaling cascades and alter gene
      expression of proteins involved in synaptic plasticity and possibly underlie the
      neuronal injury and chronic morbidities in GWI.

PMID- 29635559
TI  - Risk Factors for Training-Related Injuries During U.S. Army Basic Combat
      Training.
AB  - Background: Injuries during basic combat training (BCT) impact military health
      and readiness in the U.S. Army. Identifying risk factors is crucial for injury
      prevention, but few Army-wide studies to identify risk factors for injury during
      BCT have been completed to date. This study examines associations between
      individual and training-related characteristics and injuries during Army BCT.
      Methods: Using administrative data from the Total Army Injury and Health Outcomes
      Database (TAIHOD), we identified individuals who apparently entered BCT for the
      first time between 1 January 2002 and 30 September 2007, based on review of
      administrative records. Injuries were identified and categorized based on coded
      medical encounter data. When combined with dates of medical services, we could
      count injuries per person, identify unique injuries, and identify the quantity
      and type of medical care delivered. Regression models produced odds ratios (ORs)
      and 95% confidence intervals (CIs) to identify risk factors for injury during BCT
      (yes/no), adjusted for potential confounders. Results: Of the 278,045 (83.4%) men
      and 55,302 (16.6%) women who were apparently first-time trainees, 39.5% (n =
      109,760) of men and 60.9% (n = 33,699) of women were injured during training
      based on over 2 million recorded medical encounters entries. The large cohort
      yielded statistically significant, small magnitude associations between injury
      and all individual and training-related covariates for men, and all but medical
      accession waivers and weight for women. After adjustment, largest magnitude
      effects among men were due to age > 25 yr vs. 17-18 yr (OR = 1.83, 95% CI: 1.75,
      1.91); having been married in the past vs. being single (OR = 1.36, 95% CI: 1.24,
      1.49); rank E4-E7 vs. E1 (OR = 0.56, 95% CI: 0.53. 0.59); training at Ft. Jackson
      (OR = 0.66, 95% CI: 0.64, 0.69), Ft. Leonard Wood (OR = 0.67, 95% CI: 0.65,
      0.70), or Ft. Knox (OR = 0.69, 95% CI: 066, 0.72) vs. Ft. Benning. Odds of injury
      were highest during 2005, 2006, and 2007. After adjustment for weight and body
      mass index, taller men had higher odds of BCT injury than average height men (OR
      = 1.08, 95% CI: 1.05, 1.11). Among women, short stature (OR = 1.11; 95% CI: 1.04,
      1.19), training at Ft Leonard Wood (OR = 1.10; 95% CI: 1.04, 1.16) and evidence
      of injury prior to training based on accession waiver (OR = 1.12; 95% CI: 1.00,
      1.26) increased injury risk. Conclusions: This Army-wide analysis reveals higher
      BCT-related injury rates for both men and women than prior studies and identifies
      risk factors for injuries during BCT. The large data set allows adjustment for
      many covariates, but because statistical analysis may yield significant findings
      for small differences, results must be interpreted based on minimally important
      differences determined by military and medical professionals. Results provide
      information that may be used to adapt training or medical screening and
      examination procedures for basic trainees.

PMID- 29635561
TI  - Biomechanical Measurement and Modeling of Human Eardrum Injury in Relation to
      Blast Wave Direction.
AB  - Rupture of the eardrum or tympanic membrane (TM) is one of the most frequent
      injuries of the ear after blast exposure. To understand how the TM damage is
      related to blast wave direction, human cadaver ears were exposed to blast waves
      along three directions: vertical, horizontal, and front with respect to the head.
      Blast overpressure waveforms were recorded at the ear canal entrance (P0), near
      the TM (P1), and inside the middle ear (P2). Thirteen to fourteen cadaver ears
      were tested in each wave direction and the TM rupture thresholds were identified.
      Results show that blast wave direction affected the peak P1/P0 ratio, TM rupture
      threshold, and energy flux distribution over frequencies. The front wave resulted
      in lowest TM rupture threshold and the horizontal wave resulted in highest P1/P0
      ratio. To investigate the mechanisms of TM injury in relation to blast wave
      direction, the recorded P1 waveforms were applied onto the surface of the TM in a
      three-dimensional finite element model of the human ear and distributions of the
      stress in TM were calculated. Modeling results indicate that the sensitivity of
      TM stress change with respect to P1 pressure (dsigma/dP1) may characterize
      mechanical damage of the TM in relation to blast waves.

PMID- 29635562
TI  - Assessment of Anatomical Knowledge and Core Trauma Competency Vascular Skills.
AB  - Objectives: Surgical residents express confidence in performing specific vascular
      exposures before training, but such self-reported confidence did not correlate
      with co-located evaluator ratings. This study reports residents' self-confidence
      evaluated before and after Advanced Surgical Skills for Exposure in Trauma
      (ASSET) cadaver-based training, and 12-18 mo later. We hypothesize that residents
      will better judge their own skill after ASSET than before when compared with
      evaluator ratings. Methods: Forty PGY2-7 surgical residents performed four
      procedures: axillary artery (AA), brachial artery (BA), femoral artery exposure
      and control (FA), and lower extremity fasciotomy (FAS) at the three evaluations.
      Using 5-point Likert scales, surgeons self-assessed their confidence in
      anatomical understanding and procedure performance after each procedure and
      evaluators rated each surgeon accordingly. Results: For all the three
      evaluations, residents consistently rated their anatomical understanding (p <
      0.04) and surgical performance (p < 0.03) higher than evaluators for both FA and
      FAS. Residents rated their anatomical understanding and surgical performance
      higher (p < 0.005) than evaluators for BA after training and up to 18 mo later.
      Only for third AA evaluation were there no rating differences. Conclusions:
      Residents overrate their anatomical understanding and performance abilities for
      BA, FA, and FAS even after performing the procedures and being debriefed three
      times in 18 mo.

PMID- 29635563
TI  - TRR's Warrior Camp: An Intensive Treatment Program for Combat Trauma in Active
      Military and Veterans of All Eras.
AB  - Effective treatments for combat trauma in military service members exist, but
      barriers to care abound, including poor access, stigma, and dropout. Although the
      effects of post-traumatic stress disorder (PTSD) can be severe, recovery is
      possible when proper treatment is implemented. Trauma and Resiliency Resources,
      Inc.'s Warrior Camp (WC) program is designed to address the effects of combat
      trauma in military service members and veterans. This intensive, 7-d treatment
      incorporates eye movement desensitization and reprocessing therapy, equine
      assisted psychotherapy, yoga, and narrative writing in context of community. This
      single-group pretest-posttest design included paired t-tests and effect size
      analyses for 85 participants of WC. Outcome measures included the Mississippi
      Scale for Combat-related PTSD, the Patient Health Questionnaire, the Revised
      Adult Attachment Scales, and the Moral Injury Events Scale. Clinician
      administered measures included the Davidson Trauma Scale and the Dissociative
      Experiences Scale. All measures showed statistically significant reductions in
      distress. The effect sizes ranged from small to large. Results suggest that WC
      participants experienced significant improvement in PTSD, depression, moral
      injury, dissociation and adult attachment. Clinicians should consider the
      potential benefits of this short-term, intensive treatment when addressing combat
      related PTSD among military service members and veterans.

PMID- 29635564
TI  - Physiological Effects of Wearing Athletic Mouth Pieces While Performing Various
      Exercises.
AB  - The purpose of this study is to evaluate physiological responses associated with
      exercise using two different mouthpieces compared with not using a mouthpiece.
      Improved performance while using the PX3 Bite Regulator (PX3) may significantly
      reduce the risk of concussions by allowing an athlete to better prepare, react,
      absorb, and/or avoid impact completely compared with the restricted breathing or
      mandibular instability that occurs when using mouthguards. Twenty-three subjects
      completed a battery of five physiological tests; the 1.5-mile run, sit and reach,
      anaerobic endurance, leg press, and bench press. Each test battery was completed
      under three conditions: wearing a PX3, wearing a mouthguard, or no mouthpiece
      respectfully. The PX3 resulted in significantly faster 1.5-mile run times (667.4
      +/- 9.4 vs. 684.9 +/- 9.2 vs. 679 +/- 7.9 s, p <= 0.05) and significantly longer
      anaerobic endurance runs (311 +/- 23 vs. 283 +/- 18 vs. 286 +/- 18yds, p <= 0.05)
      compared with the mouthguard and no mouthpiece. The leg press lifts (51.8 +/- 4.1
      vs. 46.0 +/- 4.3, p <= 0.05) while wearing the PX3 were significantly greater
      than when wearing a mouthguard. There were improvements, but no significant
      differences for sit and reach (16.8 +/- 0.8 vs. 15.9 +/- 0.8 vs. 16.4 +/- 0.8
      in., p = 0.73) and bench press (17.7 +/- 1.8 vs. 17.2 +/- 1.6 vs. 17.2 +/- 1.7
      lifts, p = 0.94). The increased performance with the PX3 could be a result of
      better jaw alignment and/or decreased resistance to airflow.

PMID- 29635565
TI  - A Family's Affair: Caring for Veterans with Penetrating Traumatic Brain Injury.
AB  - Approximately 1.1 million family members are primary caregivers to post 9/11
      veterans. These military caregivers assume a role that requires a long-term
      commitment that may affect their own health status; however, the impact on health
      among military caregivers is underestimated and underrepresented. As part of a
      larger retrospective cohort study that aimed to assess the health-related
      outcomes of post 9/11 veterans with penetrating traumatic brain injury (pTBI), we
      examined the health impact of caregiving on caregivers. Caregivers (n = 66) of
      veterans with pTBI completed a survey that captured the veterans' and their own
      health-related outcomes. Surveys included veteran and caregiver
      sociodemographics, caregiver role, tasks, burden, and caregiver-reported measures
      of veterans' health and quality of life. The participants were spouses (58%) and
      parents (32%) providing full-time assistance for more than 5 yr (74%). In their
      caregiver role, they provided assistance with activities of daily living and
      emotional/social support. Forty-eight percent of these caregivers met the
      definition of experiencing clinically significant burden. Veterans with pTBI had
      other comorbidities (e.g., depression, cognitive dysfunction, and anger), which
      were associated with caregiver burden. The findings further confirm the impact of
      caregiving on health status of caregivers, specifically when assisting veterans
      with pTBI.

PMID- 29635566
TI  - PHIT for Duty, a Mobile Application for Stress Reduction, Sleep Improvement, and
      Alcohol Moderation.
AB  - Post-traumatic stress and other problems often occur after combat, deployment,
      and other military operations. Because techniques such as mindfulness meditation
      show efficacy in improving mental health, our team developed a mobile application
      (app) for individuals in the armed forces with subclinical psychological problems
      as secondary prevention of more significant disease. Based on the Personal Health
      Intervention Toolkit (PHIT), a mobile app framework for personalized health
      intervention studies, PHIT for Duty integrates mindfulness-based relaxation,
      behavioral education in sleep quality and alcohol use, and psychometric and
      psychophysiological data capture. We evaluated PHIT for Duty in usability and
      health assessment studies to establish app quality for use in health research.
      Participants (N = 31) rated usability on a 1 (very hard) to 5 (very easy) scale
      and also completed the System Usability Scale (SUS) questionnaire (N = 9).
      Results were (mean +/- SD) overall (4.5 +/- 0.6), self-report instruments (4.5 +/
      0.7), pulse sensor (3.7 +/- 1.2), sleep monitor (4.4 +/- 0.7), sleep monitor
      comfort (3.7 +/- 1.1), and wrist actigraphy comfort (2.7 +/- 0.9). The average
      SUS score was 85 +/- 12, indicating a rank of 95%. A comparison of PHIT-based
      assessments to traditional paper forms demonstrated a high overall correlation (r
      = 0.87). These evaluations of usability, health assessment accuracy,
      physiological sensing, system acceptability, and overall functionality have shown
      positive results and affirmation for using the PHIT framework and PHIT for Duty
      application in mobile health research.

PMID- 29635567
TI  - Effects on Neurons and Hippocampal Slices by Single and Multiple Primary Blast
      Pressure Waves From Detonating Spherical Cyclotrimethylenetrinitramine (RDX)
      Explosive Charges.
AB  - Threshold shock-impulse levels required to induce cellular injury and cumulative
      effects upon single and/or multiple exposures are not well characterized.
      Currently, there are few in vitro experimental models with blast pressure waves
      generated by using real explosives in the laboratory for investigating the
      effects of primary blast-induced traumatic brain injury. An in vitro indoor
      experimental platform is developed using real military explosive charges to
      accurately represent battlefield blast exposure and to probe the effects of
      primary explosive blast on dissociated neurons and tissue slices. Preliminary
      results indicate that physical insults altered membrane permeability, impacted
      cellular viability, created axonal beadings, and led to synaptic protein loss in
      hippocampal slice cultures. Injuries from blast under the conditions that were
      examined did not appear to cause immediate or sustained damage to the cells.
      Three consecutive primary blasts failed to disrupt the overall cellular integrity
      in the hippocampal slice cultures and produced a unique type of pathology
      comprised with distinct reduction in synaptic proteins before cellular
      deterioration set in. These observed changes might add to the challenges in
      regard to enhancing our understanding of the complex biochemical and molecular
      mechanisms caused by primary blast-induced injury.

PMID- 29635568
TI  - A Cluster of Exertional Rhabdomyolysis Cases in a ROTC Program Engaged in an
      Extreme Exercise Program.
AB  - Exertional rhabdomyolysis (ER) is on the rise among service members and high
      school and college athletes. Reported risk factors for ER include fitness level,
      sudden increase in exercise intensity and duration, and eccentric predominant
      exercise. This study examined an ER cluster among Reserve Officer Training Corps
      cadets who participated in a mandatory, timed, extreme conditioning program (ECP)
      workout. Forty-four cadets participated in this ECP; 11 were subsequently
      hospitalized with ER. Thirty-five cadets, including all who developed ER,
      completed a questionnaire to assess ECP times, prior fitness scores, and other ER
      risk factors. Cadets completed the ECP workout as individuals or in teams. Nine
      of 29 (31%) individual and two of 15 (13%) team participants were hospitalized
      with ER. Among the cadets, no associations were noted between hospitalization for
      ER and finish time, previous fitness scores, or dietary supplement use. The
      relative risk of developing ER was significantly increased in those who consumed
      alcohol in the week preceding the ECP (RR = 4.20; 95% CI 1.95, 9.03). In this
      cohort of Reserve Officer Training Corps cadets, an ECP resulted in a high rate
      of hospitalization for ER. Contrary to reported ER risk factors, higher baseline
      fitness was not protective. Rather, cadet knowledge that ECP performance was
      strongly linked to final cadet ranking greatly influenced intensity of effort.

PMID- 29635569
TI  - Case Report of Extracorporeal Membrane Oxygenation and Aeromedical Evacuation at
      a Deployed Military Hospital.
AB  - The U.S. Military no longer maintains overseas extracorporeal membrane
      oxygenation (ECMO) capability for patients with severe lung injury including
      acute respiratory distress syndrome (ARDS). The authors present a case of severe
      ARDS at a military hospital in Afghanistan with limited capability for rescue
      therapies to include presentation, treatment, transport, and use of ECMO in the
      deployed military environment at one Role 3 medical facility. Lack of ECMO in the
      overseas environment is a significant gap in U.S. Military medical capability.
      The authors propose a novel solution, "ECMO packs," for prepositioning at
      strategic Role 3 facilities for early intervention in patients with severe lung
      injury to close this lethal and unnecessary capability gap.

PMID- 29635570
TI  - Non-invasive Dual-Channel Broadband Diffuse Optical Spectroscopy of Massive
      Hemorrhage and Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA)
      in Swine.
AB  - Objective: To quantitatively measure tissue composition and hemodynamics during
      resuscitative endovascular balloon occlusion of the aorta (REBOA) in two tissue
      compartments using non-invasive two-channel broadband diffuse optical
      spectroscopy (DOS). Methods: Tissue concentrations of oxy- and deoxyhemoglobin
      (HbO2 and HbR), water, and lipid were measured in a porcine model (n = 10) of
      massive hemorrhage (65% total blood volume over 1 h) and 30-min REBOA superior
      and inferior to the aortic balloon. Results: After hemorrhage, hemoglobin oxygen
      saturation (StO2 = HbO2/[HbO2 + HbR]) at both sites decreased significantly (
      29.9% and -42.3%, respectively). The DOS measurements correlated with mean
      arterial pressure (MAP) (R2 = 0.79, R2 = 0.88), stroke volume (SV) (R2 = 0.68, R2
      = 0.88), and heart rate (HR) (R2 = 0.72, R2 = 0.88). During REBOA, inferior StO2
      continued to decline while superior StO2 peaked 12 min after REBOA before
      decreasing again. Inferior DOS parameters did not associate with MAP, SV, or HR
      during REBOA. Conclusions: Dual-channel regional tissue DOS measurements can be
      used to non-invasively track the formation of hemodynamically distinct tissue
      compartments during hemorrhage and REBOA. Conventional systemic measures MAP, HR,
      and SV are uncorrelated with tissue status in inferior (downstream) sites. Multi
      compartment DOS may provide a more complete picture of the efficacy of REBOA and
      similar resuscitation procedures.

PMID- 29635571
TI  - The Uniformed Services University's Surgical Critical Care Initiative (SC2i):
      Bringing Precision Medicine to the Critically Ill.
AB  - Precision medicine endeavors to leverage all available medical data in pursuit of
      individualized diagnostic and therapeutic plans to improve patient outcomes in a
      cost-effective manner. Its promise in the field of critical care remains
      incompletely realized. The Department of Defense has a vested interest in
      advancing precision medicine for those sent into harm's way and specifically
      seeks means of individualizing care in the context of complex and highly dynamic
      combat clinical decision environments. Building on legacy research efforts
      conducted during the Afghanistan and Iraq conflicts, the Uniformed Service
      University (USU) launched the Surgical Critical Care Initiative (SC2i) in 2013 to
      develop clinical- and biomarker-driven Clinical Decision Support Systems (CDSS),
      with the goals of improving both patient-specific outcomes and resource
      utilization for conditions with a high risk of morbidity or mortality. Despite
      technical and regulatory challenges, this military-civilian partnership is
      beginning to deliver on the promise of personalized care, organizing and
      analyzing sizable, real-time medical data sets to support complex clinical
      decision-making across critical and surgical care disciplines. We present the
      SC2i experience as a generalizable template for the national integration of
      federal and non-federal research databanks to foster critical and surgical care
      precision medicine.

PMID- 29635572
TI  - Validation of Visual Objective Biomarkers for Acute Concussion.
AB  - Objective: Despite an increase in the awareness and diagnosis of mild traumatic
      brain injury (mTBI), there remains a paucity of data examining the comparative
      efficacy of available assessments. This study aims to validate visual functions
      as potential biomarkers for mTBI. Methods: This case-control correlational design
      utilizes military personnel diagnosed with acute (<=72 h post-injury) mTBI (n =
      100) and age-matched controls (n = 100) to examine the relative effectiveness of
      the pupillary light reflex (PLR), near point of convergence (NPC) break, King
      Devick (KD) test time, and Convergence Insufficiency Symptom Survey (CISS) score
      to discriminate between participants with mTBI. Results: Three of the eight PLR
      parameters (i.e., average constriction velocity (ACV), average dilation velocity
      (ADV), and 75% re-dilation time; all p < 0.001) were affected in mTBI
      participants. Similarly, NPC break, KD test time, and CISS scores showed a
      statistically significant difference between groups (all p < 0.001). Area under
      the curve showed that ADV (0.82) and NPC (0.74) have the higher predictive values
      of all objective parameters. Conclusions: ADV, ACV, and NPC break are objective
      visual functions markedly affected in the acute mTBI group compared with
      controls; therefore, we proposed that they could be used as biomarkers for acute
      mTBI.

PMID- 29635573
TI  - Evaluation of a Novel Wireless Transmission System for Trauma Ultrasound
      Examinations From Moving Ambulances.
AB  - Objective: To determine if physicians trained in ultrasound interpretation
      perceive a difference in image quality and usefulness between Extended Focused
      Assessment with Sonography ultrasound examinations performed at bedside in a
      hospital vs. by emergency medical technicians minimally trained in medical
      ultrasound on a moving ambulance and transmitted to the hospital via a novel
      wireless system. In particular, we sought to demonstrate that useful images could
      be obtained from patients in less than optimal imaging conditions; that is, while
      they were in transport. Methods: Emergency medical technicians performed the
      examinations during transport of blunt trauma patients. Upon patient arrival at
      the hospital, a bedside Extended Focused Assessment with Sonography examination
      was performed by a physician. Both examinations were recorded and later reviewed
      by physicians trained in ultrasound interpretation. Results: Data were collected
      on 20 blunt trauma patients over a period of 13 mo. Twenty ultrasound-trained
      physicians blindly compared transmitted vs. bedside images using 11 Questionnaire
      for User Interaction Satisfaction scales. Four paired samples t-tests were
      conducted to assess mean differences between ratings for ambulatory and base
      images. Conclusion: Although there is a slight tendency for the average rating
      across all subjects and raters to be slightly higher in the base than in the
      ambulatory condition, none of these differences are statistically significant.
      These results suggest that the quality of the ambulatory images was viewed as
      essentially as good as the quality of the base images.

PMID- 29635574
TI  - Splenic Trauma in the Israeli Defense Forces - Do Not Underestimate Minor Trauma.
AB  - Background: The spleen is the most commonly damaged abdominal organ following
      blunt abdominal trauma (BAT), usually involving a major injury mechanism. Several
      cases of splenic rupture caused by minor BAT in the Israeli Defense Forces (IDF)
      have recently occurred. This led us to explore the demographics and mechanisms of
      trauma resulting in splenic injury among IDF personnel. Methods: All cases of
      splenic injury between 2007 and 2015 were pulled from the computerized patient
      records of the IDF. Data regarding patient demographics, injury mechanism,
      presenting symptoms, treatment, and outcomes were collected. Three independent
      physicians graded the injury mechanism as major or minor. Results: Fifty-two
      cases of splenic injury were identified. Of them, 82.7% resulted from a blunt
      trauma, 9.6% occurred after a penetrating trauma and 7.7% occurred spontaneously.
      37.2% of BAT were unanimously considered as minor. Patients who suffered minor
      trauma were more likely to experience delayed diagnosis (85.7% vs. 0% p < 0.0001)
      and had significantly less concomitant injuries (12.5% vs. 88.8% p < 0.0001). The
      presentation, treatment, and outcome of the patients were similar, regardless of
      the severity of trauma mechanism. Conclusion: Our findings indicate that although
      minor BAT results from a milder traumatic mechanism, it is a significant cause of
      splenic injury among active duty personnel. We suggest that military physicians
      maintain a high level of suspicion while managing minor BAT cases.

PMID- 29635575
TI  - Comparison of Two Tourniquets on a Mid-Thigh Model: The Israeli Silicone Stretch
      and Wrap Tourniquet vs. The Combat Application Tourniquet.
AB  - Introduction: Experience from recent conflicts underlines the dramatic impact of
      effective tourniquet use on combat casualty mortality. Although the Combat
      Application Tourniquet (CAT) is replacing the silicone band tourniquets (IST;
      "Israeli Silicone Tourniquet") in the Israeli Defense Forces, no direct
      comparison was made between them. The purpose of this study is to compare the
      performance of the two tourniquets on a mid-thigh model. Methods: Participants
      were Israeli military recruits who previously had the military first aid course.
      Each participant applied both the CAT and the IST. Applications were assessed by
      the HapMed Leg Tourniquet Trainer, which measured the applied pressure and the
      time required to reach it. Results: IST application resulted in higher rates of
      effective occlusion pressure compared with the CAT (91% vs. 73.1%, p < 0.01), and
      a higher mean occlusion pressure (41 mmHg, p < 0.01) was recorded using the IST.
      Among effective attempts, application time did not differ significantly between
      the tourniquets. Conclusion: The IST was superior to the CAT in producing
      effective occlusion pressure while not prolonging application time. These results
      may indicate that the IST remains a valid option for controlling mid-thigh
      bleeding.

PMID- 29635576
TI  - Vestibular Test Patterns in the NICoE Intensive Outpatient Program Patient
      Population.
AB  - The National Intrepid Center of Excellence (NICoE), on the campus of Walter Reed
      National Military Medical Center, was developed to help improve the lives of
      active duty service members (SMs) with traumatic brain injury (TBI) and comorbid
      behavioral health (BH) conditions. During the NICoE intensive outpatient program,
      SM who have all been identified as having some degree of TBI, undergo extensive
      interdisciplinary evaluations, including comprehensive vestibular assessment.
      These SMs sometimes present with vestibular symptoms ranging from lightheadedness
      to vertigo associated with the dual TBI/BH diagnoses, and vestibular testing
      results reported elsewhere have varied among this population. The study's purpose
      was to collate the vestibular test results obtained from a sample of the NICoE
      patients to determine if specific tests have a tendency to be abnormal in these
      SMs. Results indicate that oculomotor tests, particularly pursuit and saccade,
      were most often abnormal. The vertical subtests of the pursuit and saccade tests
      were abnormal more frequently than the horizontal subtests, suggesting that the
      vertical subtests should be utilized when evaluating the TBI population. Overall,
      oculomotor tests of vertical pursuit and saccades, as well as tests of central
      vestibular function, appear useful for detecting neurologic changes in active
      duty SMs with chronic symptoms after TBI.

PMID- 29635577
TI  - Clinical Impact of Cabin Altitude Restriction Following Aeromedical Evacuation.
AB  - Combat medical care relies on aeromedical evacuation (AE). Vital to AE is the
      validating flight surgeon (VFS) who warrants a patient is "fit to fly." To do
      this, the VFS considers clinical characteristics and inflight physiological
      stressors, often prescribing specific interventions such as a cabin altitude
      restriction (CAR). Unfortunately, limited information is available regarding the
      clinical consequences of a CAR. Consequently, a dual case-control study (CAR
      patients versus non-CAR patients and non-CAR patients flown with a CAR versus non
      CAR patients) was executed. Data on 1,114 patients were obtained from TRANSCOM
      Regulating and Command and Control Evacuation System and Landstuhl Regional
      Medical Center trauma database (January 2007 to February 2008). Demographic and
      clinical factors essentially showed no difference between groups; however, CAR
      patients appeared more severely injured than non-CAR patients. Despite being
      sicker, CAR patients had similar clinical outcomes when compared with non-CAR
      patients. In contrast, despite an equivocal severity picture, the non-CAR
      patients flown with a CAR had superior clinical outcomes when compared with non
      CAR patients. It appeared that the CAR prescription normalized severely injured
      to moderately injured and brought moderately injured into a less morbid state.
      These results suggest that CAR should be seriously considered when evacuating
      seriously ill/injured patients.

PMID- 29635578
TI  - Preliminary Evidence for Improvement in Symptoms, Cognitive, Vestibular, and
      Oculomotor Outcomes Following Targeted Intervention with Chronic mTBI Patients.
AB  - Introduction: To determine if targeted, active interventions would improve
      symptoms and impairment in previously intractable patients with chronic mild
      traumatic brain injury (mTBI). Materials and Methods: Twenty-six (20 males; 6
      females) out of 51 (51%) former military and civilian patients with chronic (1-3
      yr) mTBI enrolled in the TEAM traumatic brain injury (TBI) study completed both
      an initial and 6-mo post-intervention comprehensive mTBI assessment including
      symptoms (Post-concussion Symptom Scale [PCSS], Dizziness Handicap Inventory
      [DHI]), cognitive (Immediate Post-concussion Assessment and Cognitive Testing
      [ImPACT]), vestibular/oculomotor (Vestibular/Ocular Motor Screening [VOMS]),
      balance (Activities-specific Balance Confidence [ABC] scale, Balance Error
      Scoring System [BESS]), and cervical (Neck Disability Index [NDI]). Patients were
      prescribed progressive, targeted interventions and therapies (e.g., behavioral,
      vestibular, vision, and exertion) that matched their mTBI clinical profile. A
      series of paired t-tests adjusted for multiple corrections were used to compare
      pre- and post-intervention assessment scores. Results: Patients demonstrated
      significant improvement from pre- to post-intervention on total symptoms (t =
      2.69, p = 0.01), verbal memory (t = -1.96, p = 0.05), ABC balance score (t = 
      2.05, p = 0.05), smooth pursuits (t = 2.32, p = 0.04), near-point convergence
      distance (t = -3.58, p = 0.01), vestibular ocular reflex (t = 2.31, p = 0.03),
      and visual motion sensitivity (t = 2.43, p = 0.03). Conclusions: Previously
      recalcitrant patients with chronic complex mTBI demonstrated significant
      improvement in symptoms, cognitive, vestibular, oculomotor, and balance function
      following targeted interventions.

PMID- 29635579
TI  - Coagulopathy and Mortality in Combat Casualties: Do the Kidneys Play a Role?
AB  - Background: Acute traumatic coagulopathy (ATC) is a common condition after
      traumatic injury and is known to be associated with an increase in morbidity and
      mortality in trauma patients. ATC has been implicated as a causative factor in
      both early hemorrhage and late organ failure in this population, yet the
      pathophysiology remains largely unknown. Additionally, acute kidney injury (AKI)
      is a common condition among critically injured trauma patients. AKI has been
      associated with an elevated International Normalized Ratio (INR) and warfarin
      use, but its development has not been well studied in the setting of ATC. We
      hypothesized that the presence of ATC influences the development of AKI and may
      mediate mortality in combat casualties. Methods: Data were obtained from the
      Department of Defense Trauma Registry, Medical Data Store and Composite
      Healthcare System, and the Armed Forces Medical Examiner System. A retrospective
      review was conducted of US service members injured in Iraq or Afghanistan between
      February 1, 2002 and February 1, 2011, who required ICU level care and survived
      evacuation out of theater. Exclusions were made for missing data. Cox
      proportional hazard regression was performed to determine the effect of ATC (a
      priori defined as first INR > 1.3) on the development of AKI. Further analysis
      was conducted to determine the influence of these variables on 30-d mortality,
      and multiple sensitivity analyses were performed to determine the effect of ATC
      on both AKI and mortality. Results: A total of 1,288 patients were identified for
      analysis. ATC was a risk factor for subsequent AKI after adjustment (HR 1.67, 95%
      CI 1.28-2.18; p < 0.001). However, ATC was not a risk factor for mortality after
      adjustment in the full model (HR 1.87, 95% CI 0.95-3.65; p = 0.069). On
      sensitivity analyses exploring alternate definitions of ATC, an INR of 1.2
      remained associated with AKI (HR 1.46, 95% CI 1.13-1.88; p = 0.004) and an INR of
      1.5 became significant for mortality (HR 1.76, 95% CI 1.32-2.35; p < 0.001).
      Conclusion: ATC is independently associated with the development of AKI. Although
      ATC is associated with mortality in the unadjusted model, it is not significant
      after adjustment for AKI. This implies that the kidneys may play a role in the
      adverse outcomes observed after ATC. Increased awareness and monitoring for
      coagulopathy and the subsequent development of AKI in combat casualty patients
      may lead to earlier diagnosis and treatment of these conditions, possibly
      decreasing morbidity and mortality.

PMID- 29635580
TI  - Trabectome-Initiated Gonioscopy-Assisted Transluminal Trabeculotomy.
AB  - Introduction: To introduce a trabectome-initiated gonioscopy-assisted
      transluminal trabeculotomy (TIGATT) procedure and to report preliminary results.
      Materials and Methods: A preliminary case series of eight patients who have
      undergone the newly proposed TIGATT procedure is presented. TIGATT is a new
      concept that modifies established techniques by replacing the initial goniotomy
      incision of gonioscopy-assisted transluminal trabeculotomy (GATT) with an ab
      interno trabeculectomy ablation utilizing the trabectome. All surgeries were
      performed by a single surgeon (W.I.K.) between November 2014 and October 2015 in
      adults with primary open-angle glaucoma. Recorded outcome measures were
      intraocular pressure (IOP), number of medications, and complications. Results:
      Eight patients with an age range of 63-93 yr underwent TIGATT with at least 3 mo
      of follow-up. Five of the eight initial patients had follow-up to 2 yr. The mean
      pre-operative IOP was 25 mmHg (standard deviation [SD] 7.0) on four medications
      (SD 1.1). The mean post-operative IOP at 3 mo was 14 mmHg (SD 1.8) on two
      medications (SD 1.3). The average decrease in IOP was 9.9 mmHg (SD 7.5) with an
      average decrease in medications of two (SD 1.4) at 3 mo. At 2 yr, the mean post
      operative IOP was 14 mmHg (SD 3.2) on one medication (SD 1.1). The average
      decrease in IOP was 7.8 mmHg (SD 3.1) with an average decrease in medications of
      two (SD 1.8). There were two treatment failures that required further glaucoma
      surgery and one patient was lost to follow-up. Conclusions: The preliminary
      results and safety profile for TIGATT are promising and appear at least
      comparable with previously published results for both GATT and trabectome.
      Initiating the transluminal trabeculotomy with trabectome clearly exposes
      Schlemm's canal and facilitates threading the microcatheter into the canal.
      Additionally, if the 360-degree trabeculotomy cannot be completed because of an
      incompletely patent Schlemm's canal, the patient will at least have a trabectome
      ablation that can serve as their glaucoma surgery.

PMID- 29635581
TI  - Simplified Method for Rapid Field Assessment of Visual Acuity by First Responders
      After Ocular Injury.
AB  - Objective: Initial visual acuity after ocular injury is an important measure, as
      it is an accurate predictor of final visual outcome and gives a rapid estimation
      of the overall severity of the injury, thereby aiding evacuation prioritization.
      We devised a simple method for rapidly assessing visual acuity in the field
      without having to rely on formal screening cards. Methods: Using common objects,
      icons, and text found in the injury zone - for example, common military name
      tapes, rank insignias, patches, emblems, and helmet camouflage bands, which will
      be known collectively as the Army Combat Optotypes (ACOs) - a Snellen-equivalent
      method of assessing visual acuity was devised and correlated to the ocular trauma
      score (OTS). Results: Ability to read the ACOs at 2, 3, and 5 ft correlates with
      acuities in the range from 20/20 to 20/400. Identification of ACOs with visual
      acuity of 20/50 and 20/200 approximates important inflection points of severity
      for the OTS. Conclusion: Accurately assessing visual acuity in the field after
      ocular injury provides essential information but does not require sophisticated
      screening equipment. Pertinent and accurate acuities can be rapidly estimated
      using commonly available text or graphical icons such as standard name tapes,
      patches, and rank insignias.

PMID- 29635582
TI  - Stability of Fibrinogen Concentrate in Human Blood Samples: An In Vitro Study.
AB  - Objectives: This study was designed to assess the stability and functional
      activity of fibrinogen concentrates subjected to the changes in temperature and
      duration observed in field conditions. Methods: Fibrinogen concentrate was stored
      at -20 degrees C (12 vials), 22 degrees C (12 vials), and 50 degrees C with 80%
      humidity (12 vials), for up to 6 mo. At each temperature, three vials of
      fibrinogen concentrate were taken out at 0, 1, 3, and 6 mo and reconstituted. On
      analysis days, blood samples were taken from a single healthy donor to collect
      plasma samples. The donor plasma was mixed with commercial fibrinogen-deficient
      plasma to make fibrinogen-adjusted plasma (FAP). An aliquot of the reconstituted
      fibrinogen concentrate was used for quantification of stored fibrinogen content
      (using STA-R) and function (Rotem - Fibtem) in FAP. Results: At 22 degrees C for
      0, 1, 3, and 6 mo, there were no significant changes observed in fibrinogen
      content (1,223 +/- 42 mg/vial, 1,286 +/- 86 mg/vial, 1,234 +/- 76 mg/vial, and
      1,178 +/- 64 mg/vial), prothrombin time (13.5 +/- 0.1 s, 13.7 +/- 0.6 s, 13.3 +/-
      0.4 s, and 13.7 +/- 0.2 s), or activated partial thromboplastin time (31.1 +/-
      0.2 s, 32.0 +/- 0.2 s, 31.5 +/- 0.2 s, and 32.0 +/- 0.8 s), respectively. There
      were also no significant changes observed in any of the Fibtem measurements.
      Similarly, no differences were observed in these variables over time at -20
      degrees C and 50 degrees C with 80% humidity. Conclusions: Fibrinogen concentrate
      maintained its content and function when stored at -20 degrees C to 50 degrees C
      with up to 80% humidity for 6 mo.

PMID- 29635583
TI  - Development of the Warfighter's Hearing Health Instructional (WHHIP) Primer App.
AB  - The Warfighter's Hearing Health Instructional Primer (WHHIP) is a supplemental
      tool for military hearing conservation programs (MHCPs) and can be accessed by
      the warfighter on his/her own personal mobile phone. A gap was identified for a
      supplement to MHCPs that is easily accessible by warfighters to improve hearing
      health knowledge. The WHHIP aims to instruct the warfighter in best hearing
      health practices. To do so, four activities are included: Learn, Demos, HPD
      Check, and Glossary. Learn and Glossary allow the warfighter to scroll through
      various informational topics related to hearing conservation - including videos,
      descriptions of noise, and results of hearing tests. In the Demos activity, the
      warfighter can explore the difficulties that hearing loss and tinnitus pose to
      sound and speech identification. The HPD Check feature allows the warfighter to
      take a picture of the fit of hearing protection devices (HPDs) in his/her own
      ears then compare the images to ones that he/she had previously taken or of
      standard images of good fitting devices. The WHHIP is an easily accessed
      reference tool available for free via Google Play; if a warfighter has a question
      or concern regarding his/her hearing health, the WHHIP can be used to verify or
      improve knowledge.

PMID- 29635584
TI  - Olfactory Testing Informs the Decision Process to Obtain Advanced Neuroimaging in
      Traumatic Brain Injury.
AB  - The purpose of this article is to examine the usefulness of olfactory testing as
      a tool for the evaluation or stratification of traumatic brain injury (TBI)
      patients. Olfactory dysfunction is more likely to be overlooked by both the
      patient and the provider, especially in the acute setting, in contrast to
      deficits in other senses like vision or hearing. This is a retrospective clinical
      analysis (case series) of eight active duty service members referred to ear,
      nose, and throat clinic at Walter Reed National Military Medical Center during a
      2-yr period between March 2014 and March 2016 for subspecialist evaluation of
      suspected olfactory impairment after an exposure to closed head trauma. Advanced
      neuroimaging revealed evidence of frontal lobe injury in all eight patients,
      which was subtle and subcentimeter in half of the cases, best demonstrated with
      high-resolution imaging in the coronal plane. In this article, we discuss the
      correlation between olfactory dysfunction and brain pathology in both TBI and non
      TBI settings. We then provide our recommendation for an orbit magnetic resonance
      imaging (MRI) to evaluate the inferior frontal lobes and olfactory bulbs in
      patients with unexplained anosmia.

PMID- 29635585
TI  - Observations of Pediatric Disease Prevalence from Pacific Partnership 2015.
AB  - Pacific Partnership is an ongoing yearly humanitarian assistance mission to
      Pacific Rim countries. Although many case reports and surgical successes have
      been documented, few data have been published specifically about the primary care
      mission. This article analyzes outpatient pediatric data collected during Pacific
      Partnership 2015. Eleven different providers documented care delivered to
      children from birth through age 18 yr, inclusive. Personally de-identified data
      were entered into spreadsheets, sorted according to country visited, and analyzed
      with IBM SPSS software looking for disease frequency. One thousand eighty-seven
      pediatric patients were seen across Fiji, Papua New Guinea (PNG), and the
      Philippines (PI). Asthma was the first, second, and third most prevalent
      diagnosis in PNG, Fiji, and PI, with a relative proportion of the total patients
      seen at 5.4%, 7.2%, and 5%, respectively. In PI, 123 cases of upper respiratory
      infection were seen, more than four times the next most common diagnosis of
      normal exam. Thirty-six patients with scabies were seen in Fiji (number 1), with
      abdominal pain at number 3 (26 cases, 6.5%). Surprisingly, helminths were rarely
      seen, comprising the sixteenth and fourteenth most common diagnoses in Fiji and
      PI and only two cases in PNG. Future Pacific Partnership missions can plan
      medication stock, personnel assignment, equipment needs, and educational
      literature based on these data.

PMID- 29635586
TI  - Hemodilution and Endothelial Cell Regulation of Whole Blood Coagulation.
AB  - Background: Beyond localized damage to the circulatory system and surrounding
      tissue, trauma stresses endothelial cells throughout the vasculature, potentially
      leading to hemorrhagic or thrombotic complications away from the injury site.
      Objective: Use a whole blood endothelial cell model to define the effects of
      crystalloid fluid therapy on protein C pathway regulation of tissue factor
      initiated coagulation. Methods: Tissue factor-initiated coagulation was studied
      in the presence of EA.hy926 cells. Blood was diluted to 70% or 40% using normal
      saline or lactated ringers. Analyses of coagulation dynamics included clot times,
      thrombin formation (thrombin-antithrombin complex), FV activation/inactivation,
      fibrinogen consumption, FXIII activation, and platelet activation. Results: In
      all donors, the onset of thrombin generation was not altered in 70% blood using
      either diluent; with the blood component reduced to 40%, clot time was prolonged
      two-fold when normal saline was utilized but was unchanged with lactated ringers.
      The timing of the activations of FV, fibrinogen, and platelets paralleled the
      effects of dilution on clot times. Extensive inactivation of FVa was observed in
      undiluted blood and where lactated ringers was the diluent but not in trials with
      40% blood/60% normal saline. Conclusion: Feedback inhibition of tissue factor
      initiated coagulation by the protein C pathway is not compromised by hemodilution
      with crystalloids.

PMID- 29635587
TI  - Combat Helmet Suspension System Stiffness Influences Linear Head Acceleration and
      White Matter Tissue Strains: Implications for Future Helmet Design.
AB  - Combat helmets are expected to protect the warfighter from a variety of blunt,
      blast, and ballistic threats. Their blunt impact performance is evaluated by
      measuring linear headform acceleration in drop tower tests, which may be
      indicative of skull fracture, but not necessarily brain injury. The current study
      leverages a blunt impact biomechanics model consisting of a head, neck, and
      helmet with a suspension system to predict how pad stiffness affects both (1)
      linear acceleration alone and (2) brain tissue response induced by both linear
      and rotational acceleration. The approach leverages diffusion tensor imaging
      information to estimate how pad stiffness influences white matter tissue strains,
      which may be representative of diffuse axonal injury. Simulation results
      demonstrate that a softer pad material reduces linear head accelerations for mild
      and moderate impact velocities, but a stiffer pad design minimizes linear head
      accelerations at high velocities. Conversely, white matter tract-oriented strains
      were found to be smallest with the softer pads at the severe impact velocity. The
      results demonstrate that the current helmet blunt impact testing standards'
      standalone measurement of linear acceleration does not always convey how the
      brain tissue responds to changes in helmet design. Consequently, future helmet
      testing should consider the brain's mechanical response when evaluating new
      designs.

PMID- 29635588
TI  - Healthy Active Duty Military with Lifetime Experience of Mild Traumatic Brain
      Injury Exhibits Subtle Deficits in Sensory Reactivity and Sensory Integration
      During Static Balance.
AB  - Postural control and stress reactivity were investigated in active duty coast
      guard personnel to determine whether they are sensitive to lifetime effects of
      mild traumatic brain injury (mTBI). A custom-designed and validated virtual
      reality-based computerized posturography device was used to assess postural
      stability, whereas emotional reactivity was assessed using the acoustic startle
      response (ASR), and neurocognitive performance was assessed using the defense
      automated neurobehavioral assessment (DANA). It was hypothesized that residual
      and subtle postural control imbalance and deficits in cognitive and sensory
      reactivity would be evident in those reporting multiple lifetime mTBI. Active
      duty military personnel (N = 36; 7 females and 29 males) with no Deployment
      Limiting Medical Condition were recruited and tested on all assessments. Medical
      history information provided a history of head injury. Thirty-nine percent of
      participants reported having a previous mTBI (nine reporting one and five
      reporting more than one incident). No participant had experienced a head injury
      within the past year and all were symptom free. A significant effect of number of
      mTBI was found in the postural assessment (p = 0.002). Lifetime mTBI was
      associated with suppressed ASR magnitude (p = 0.03) but did not affect
      neurocognitive performance. The current findings provide new insight into ongoing
      controversies concerning sensitivity to functional deficits following mTBI and
      when the window for treatment or restoration ends.

PMID- 29635589
TI  - Operation Brain Trauma Therapy: 2016 Update.
AB  - Operation brain trauma therapy (OBTT) is a multi-center, pre-clinical drug and
      biomarker screening consortium for traumatic brain injury (TBI). Therapies are
      screened across three rat models (parasagittal fluid percussion injury,
      controlled cortical impact [CCI], and penetrating ballistic-like brain injury).
      Operation brain trauma therapy seeks to define therapies that show efficacy
      across models that should have the best chance in randomized clinical trials
      (RCTs) and/or to define model-dependent therapeutic effects, including TBI
      protein biomarker responses, to guide precision medicine-based clinical trials in
      targeted pathologies. The results of the first five therapies tested by OBTT
      (nicotinamide, erythropoietin, cyclosporine [CsA], simvastatin, and
      levetiracetam) were published in the Journal of Neurotrauma. Operation brain
      trauma therapy now describes preliminary results on four additional therapies
      (glibenclamide, kollidon-VA64, AER-271, and amantadine). To date, levetiracetam
      was beneficial on cognitive outcome, histology, and/or biomarkers in two models.
      The second most successful drug, glibenclamide, improved motor function and
      histology in CCI. Other therapies showed model-dependent effects (amantadine and
      CsA). Critically, glial fibrillary acidic protein levels predicted treatment
      effects. Operation brain trauma therapy suggests that levetiracetam merits
      additional pre-clinical and clinical evaluation and that glibenclamide and
      amantadine merit testing in specific TBI phenotypes. Operation brain trauma
      therapy has established that rigorous, multi-center consortia could revolutionize
      TBI therapy and biomarker development.

PMID- 29635590
TI  - Two-Stage Osseointegrated Reconstruction of Post-traumatic Unilateral
      Transfemoral Amputees.
AB  - A new technique called osseointegration was introduced recently by intimately
      connecting the artificial limb prosthesis to the residual bone, eliminating the
      problematic socket-residuum interface. The objective here is to describe the two
      stage strategy for the osseointegrated reconstruction of amputated limbs and
      discuss the clinical outcomes of the procedure. This is a prospective case series
      of 37 post-traumatic unilateral transfemoral amputees with a minimum 2-yr follow
      up. Outcome measures included the Questionnaire for persons with a Transfemoral
      Amputation (Q-TFA), the Short Form Health Survey 36 (SF-36), the 6 Minute Walk
      Test (6MWT), and Timed Up and Go (TUG) tests. Adverse events including infection,
      revision surgery, fractures, and implant failures were reported. Clinical
      outcomes for all outcome measures were significantly improved at follow-up.
      Twelve participants were wheelchair bound pre-operatively; however, all 12 were
      able to ambulate after osseointegrated reconstruction. Sixteen patients
      experienced infection episodes but were managed successfully without the need for
      implant removal. One periprosthetic fracture occurred due to increased activity,
      which was revised successfully. These results confirm that the procedure is a
      suitable alternative for post-traumatic unilateral transfemoral amputees
      experiencing socket-related discomfort, with the potential to reduce recovery
      time compared with other treatment protocols.

PMID- 29635591
TI  - Longitudinal Investigation of Neurotrauma Serum Biomarkers, Behavioral
      Characterization, and Brain Imaging in Soldiers Following Repeated Low-Level
      Blast Exposure (New Zealand Breacher Study).
AB  - "Breachers" (dynamic entry personnel) are routinely exposed to low-level blast
      overpressure during training and occupational duties. Data were collected from 22
      military breachers (mean 29.7 yr) over a 5-yr period to characterize the
      longitudinal effects of repeated low-level blast overpressure exposure. None of
      the participants reported a diagnosed concussion during the study period. Blood
      based biomarker concentrations (n = 22) showed either no significant change or a
      significant decrease over time. Neurocognitive performance (n = 20) and symptom
      reporting (n = 22) did not change over time. Neuroimaging analyses resulted in no
      significant differences for within-subject (baseline vs follow-up, n = 8) and
      between-subject (naive, n = 5 vs experienced, n = 8) comparisons. Changes to
      training doctrine mid-study reduced blast exposure (< 4 psi) and may have
      mitigated any measurable effects associated with long-term, low-level blast
      exposure. The results suggest that the first 5 yr of a breaching career in
      healthy, young individuals is unlikely to result in measurable effects when
      overpressure exposure is maintained within the 4 psi safe limit. The lack of any
      significant changes in these operators suggests that either no identifiable
      injuries occurred and/or measurement tools may not be sensitive enough to
      identify any negative subconcussive effects.

PMID- 29635592
TI  - Protective Effects of Psychological Strengths Against Psychiatric Disorders Among
      Soldiers.
AB  - This study prospectively examined psychological strengths targeted in U.S. Army
      training programs as predictors of psychiatric diagnosis in active duty soldiers.
      At baseline, the cohort (140,584 soldiers) was without psychiatric disorder.
      Soldiers were then followed for 2 yr and classified as healthy, or acquiring a
      psychiatric diagnosis (adjustment disorder, anxiety disorder, depression, or post
      traumatic stress disorder), or being prescribed psychotropic medication without a
      psychiatric diagnosis. Soldiers who remained healthy reported significantly
      higher strengths scores at baseline, compared with soldiers who were diagnosed
      with a psychiatric disorder. In addition, soldiers in the worst strengths decile
      were twice as likely to develop a psychiatric disorder, compared with soldiers in
      the top 50% on baseline strengths. Strengths afforded the greatest protection
      against depression. Offering tailored resilience training programs could help the
      Army steel vulnerable soldiers against the challenges of life, military training,
      and combat.

PMID- 29635593
TI  - Forward.

PMID- 29635594
TI  - Development of a Non-invasive Cerebrovascular Status Algorithm to Estimate
      Cerebral Perfusion Pressure and Intracranial Pressure in a Porcine Model of Focal
      Brain Injury.
AB  - Background: New tools for diagnosis, monitoring, and treatment of elevated
      intracranial pressure (ICP) or compromised cerebral perfusion pressure (CPP) are
      urgently needed to improve outcomes after brain injury. Previous success in
      applying advanced data analytics to build precision monitors based on large,
      noisy sensor datasets suggested applying the same approach to monitor
      cerebrovascular status. In these experiments, a new algorithm was developed to
      estimate ICP and CPP using the arterial pressure waveform. Methods: Sixty-five
      porcine subjects were subjected to a focal brain injury to simulate a mass lesion
      with elevated ICP. The arterial pressure waveform and the measured ICP from these
      subjects during injury and treatment were then utilized to develop and calibrate
      an ICP and CPP estimation algorithm. These estimation algorithms were then
      subsequently evaluated on 14 new subjects. Results: The root mean square
      difference between actual ICP and estimated ICP was 2.0961 mmHg. The root mean
      square difference between the actual CPP and the estimated CPP was 2.6828 mmHg.
      Conclusion: A novel ICP or CPP monitor based on the arterial pressure signal
      produced a very close approximation to actual measured ICP and CPP and warrants
      further evaluation.

PMID- 29635595
TI  - A Retrospective Cohort Study of QuickDASH Scores for Three Hand Therapy Acute
      Upper Limb Conditions.
AB  - Introduction: The QuickDASH is a valid and reliable outcome measure widely used
      to assess the function and pain in arm, shoulder, and hand disabilities. A recent
      study introduced a QuickDASH 80% cut point test to gauge patients at risk of poor
      outcomes. However, the utility of this test has not been validated. Purpose: To
      determine typical QuickDASH scores for three upper limb conditions and to test
      the sensitivity and specificity of the QuickDASH 80% cut point test in predicting
      patients at risk of poor outcomes. Methods: This is a retrospective study with a
      total of 406 patient records for whom QuickDASH scores were examined. The
      sensitivity and specificity of the QuickDASH 80% cut point test was investigated
      for three acute upper limb conditions seen in hand therapy: surgical distal
      radius fracture, nonsurgical lateral epicondylitis, and carpal tunnel release.
      Results: Typical scores were determined for three upper limb conditions. The
      QuickDASH 80% cut point test per upper limb condition returned poor sensitivity
      between 28.57% and 41.67%. Conclusion: The results did not support the QuickDASH
      80% cut point test as a predictor of final outcome in these three patient
      populations. Patients with the worse initial 20% scores were not correctly
      classified as worse 20% final scores. This study provides summary data from three
      upper limb conditions to provide clinicians with comparison data to establish
      goals and educate patients.

PMID- 29635596
TI  - A Fast-Running, End-to-End Concussion Risk Model for Assessment of Complex Human
      Head Kinematics.
AB  - An end-to-end, mechanism-based concussion risk model, linking head motion to
      axonal injury, has been demonstrated to predict concussion outcomes with greater
      sensitivity and specificity than external correlates such as peak head
      acceleration. The development of this model was driven by the need to more
      accurately translate head-worn sensor measurements into injury assessment in near
      real time. The full end-to-end model is a detailed multi-scale model, composed of
      complex components (e.g., a human head finite element model), is computationally
      expensive, and requires specialized software. For practicality, this research
      level model must be simplified into a standalone, fast-running algorithm that can
      be embedded on the microprocessor of a head-worn sensor. This article describes
      the development of a simplified, fast-running algorithm that delivers comparable
      results to those of the full end-to-end model. The dynamic axonal response of the
      human head finite element model to head motion is mathematically modeled using a
      lumped parameter system fitted to the finite element model response for a range
      of head motions. The other component models of the full end-to-end model were
      similarly reduced. For the same head kinematic scenarios, the probabilities of
      concussion obtained from the end-to-end model and from the simplified algorithm
      are compared well.

PMID- 29635597
TI  - A Step Toward Identifying Sources of Medical Errors: Modeling Standards of Care
      Deviations for Different Disease States.
AB  - Objective: To examine the feasibility of utilizing electronic health records
      (EHR) to determine a metric for identifying physician diagnostic and treatment
      deviations in standards of care for different disease states. Methods: A Boolean
      rule-based model compared deviations in standards of care across four disease
      states: diabetes, cardiovascular disease, asthma, and rheumatoid arthritis. This
      metric was used to identify the relationship between physician deviations in
      standards of care procedures, before and after diagnosis, for 76 internal
      medicine physicians. Results: The Boolean-rule-based model identified patterns of
      standards of care deviation for the physicians before diagnosis and during
      treatment. The deviations identified for each of the four disease states were
      then related to Continuing Medical Education courses that could support further
      training. The rule-based model was extended and improved by including system and
      process aspects of medical care that are not specifically related to the
      physician, yet potentially have an impact on the physician's decision to deviate
      from the standards of care. Conclusion: The Boolean-rule-based approach provided
      a means to systematically mine EHRs and use these data to assess deviations in
      standards of care that could identify quality of care issues stemming from system
      processes or the need for specific CME for a physician.

PMID- 29635598
TI  - Retrospective Analysis of Esophageal Heat Transfer for Active Temperature
      Management in Post-cardiac Arrest, Refractory Fever, and Burn Patients.
AB  - Core temperature management is an important aspect of critical care; preventing
      unintentional hypothermia, reducing fever, and inducing therapeutic hypothermia
      when appropriate are each tied to positive health outcomes. The purpose of this
      study is to evaluate the performance of a new temperature management device that
      uses the esophageal environment to conduct heat transfer. De-identified patient
      data were aggregated from three clinical sites where an esophageal heat transfer
      device (EHTD) was used to provide temperature management. The device was
      evaluated against temperature management guidelines and best practice
      recommendations, including performance during induction, maintenance, and
      cessation of therapy. Across all active cooling protocols, the average time-to
      target was 2.37 h and the average maintenance phase was 22.4 h. Patients spent
      94.9% of the maintenance phase within +/-1.0 degrees C and 67.2% within +/-0.5
      degrees C (574 and 407 measurements, respectively, out of 605 total). For warming
      protocols, all of the patient temperature readings remained above 36 degrees C
      throughout the surgical procedure (average 4.66 h). The esophageal heat transfer
      device met performance expectations across a range of temperature management
      applications in intensive care and burn units. Patients met and maintained
      temperature goals without any reported adverse events.

PMID- 29635599
TI  - Evaluation of Environmental Sensors During Laboratory Direct and Indirect Head
      Exposures.
AB  - With the prevalence of traumatic brain injury (TBI) in the military and
      athletics, several commercial and military environmental sensors (ES) have been
      developed to quantify head impact exposures. The performance of five ES in
      controlled laboratory exposures from direct and indirect loadings, and the effect
      on impact protection and dynamic retention of the worn Advanced Combat Helmet
      (ACH) was evaluated. Direct impacts were conducted on a drop tower and indirect
      impacts used a mini-sled. The ES data were compared with laboratory sensors
      through cross-correlation and comparison of peak values. The effects of ES on
      dynamic retention were assessed using a one-way ANOVA with Tukey's post hoc
      analysis against baseline ACH performance. Two ES provided data during the blunt
      impact tests: one, attached to the side of the headform, correlated well (phi >
      0.92) with the laboratory data; the other, mounted in the helmet crown,
      calculated peak headform velocity, which predicted laboratory velocity well.
      During indirect impact tests, one environmental sensor (attached to the side of
      the headform) provided usable data, which correlated well (phi > 0.92) with
      laboratory data. The inclusion of the environmental sensors did not introduce any
      safety hazards during the blunt impact attenuation tests or the dynamic retention
      tests.

PMID- 29635600
TI  - Suicide Rates Among Active Duty Service Members Compared with Civilian
      Counterparts, 2005-2014.
AB  - The objective of this study was to compare military suicide rates with civilian
      suicide rates, adjusting for age and sex differences that exist between the two
      populations. The number of active component (AC) service members whose manner of
      death was certified as suicide was determined for specific age and sex groups for
      each year from 2005 to 2014. Indirect standardization was then used to determine
      the expected number of suicides for each age/sex group, based on the U.S. suicide
      rates for the corresponding age/sex groups obtained from the Centers for Disease
      Control and Prevention's Web-based Injury Statistics Query and Reporting System.
      Although suicide rates among U.S. active duty Service Members were found to
      increase between 2005 and 2009, overall age- and sex-adjusted AC suicide rates
      were lower than or comparable to civilian rates every year of the study period.
      When suicide numbers were analyzed within specific age and sex categories, there
      was a significant association between higher suicide incidence and AC military
      status for 17-29-yr-old females in 2010, 2012, and 2014, and a significant
      association between lower suicide incidence and AC military status for 25-49 -yr
      old males in some years.

PMID- 29635601
TI  - Preliminary Investigation of Skull Fracture Patterns Using an Impactor
      Representative of Helmet Back-Face Deformation.
AB  - Military combat helmets protect the wearer from a variety of battlefield threats,
      including projectiles. Helmet back-face deformation (BFD) is the result of the
      helmet defeating a projectile and deforming inward. Back-face deformation can
      result in localized blunt impacts to the head. A method was developed to
      investigate skull injury due to BFD behind-armor blunt trauma. A representative
      impactor was designed from the BFD profiles of modern combat helmets subjected to
      ballistic impacts. Three post-mortem human subject head specimens were each
      impacted using the representative impactor at three anatomical regions (frontal
      bone, right/left temporo-parietal regions) using a pneumatic projectile launcher.
      Thirty-six impacts were conducted at energy levels between 5 J and 25 J.
      Fractures were detected in two specimens. Two of the specimens experienced
      temporo-parietal fractures while the third specimen experienced no fractures.
      Biomechanical metrics, including impactor acceleration, were obtained for all
      tests. The work presented herein describes initial research utilizing a test
      method enabling the collection of dynamic exposure and biomechanical response
      data for the skull at the BFD-head interface.

PMID- 29635602
TI  - A Review of Casualties Transported to Role 2 Medical Treatment Facilities in
      Afghanistan.
AB  - Critically injured trauma patients benefit from timely transport and care.
      Accordingly, the provision of rapid transport and effective treatment
      capabilities in appropriately close proximity to the point of injury will
      optimize time and survival. Pre-transport tactical combat casualty care, rapid
      transport with en route casualty care, and advanced damage control resuscitation
      and surgery delivered early by small, mobile, forward-positioned Role 2 medical
      treatment facilities have potential to reduce morbidity and mortality from
      trauma. This retrospective review and descriptive analysis of trauma patients
      transported from Role 1 entities to Role 2 facilities in Afghanistan from 2008 to
      2014 found casualties to be diverse in affiliation and delivered by various types
      and modes of transport. Air medical evacuation provided transport for most
      patients, while the shortest transport time was seen with air casualty
      evacuation. Although relatively little data were collected for air casualty
      evacuation, this rapid mode of transport remains an operationally important
      method of transport on the battlefield. For prehospital care provided before and
      during transport, continued leadership and training emphasis should be placed on
      the administration and documentation of tactical combat casualty care as
      delivered by both medical and non-medical first responders.

PMID- 29635603
TI  - Evaluations of Sexual Assault Prevention Programs in Military Settings: A
      Synthesis of the Research Literature.
AB  - The prevention of sexual assault (SA) in the U.S. military is a significant
      priority. This study applied the Preferred Reporting Items for Systematic Reviews
      and Meta-Analyses (PRISMA) guidelines to a literature search that identified
      research evaluating SA prevention programs conducted within military settings.
      Only six studies published between 2005 and 2016 met criteria for inclusion in
      the review. Studies demonstrated high heterogeneity in the: (1) conceptual
      framework of the prevention approach; (2) target population and timing of
      administration; (3) study recruitment methods; (4) methodological design; (5)
      method of delivery, program dosage and theory of change; and (6) outcome
      administration and efficacy. Scientific rigor according to the Oxford Center for
      Evidence-based Medicine was also variable. Several gaps in the research base were
      identified. Specifically, research evaluating SA prevention programs have only
      been conducted among U.S. Army and U.S. Navy samples. Most studies did not
      examine whether program participation was associated with reductions in rates of
      sexual violence. Studies also lacked utilization of a long-term follow-up period.
      Additionally, studies did not reflect the types of SA prevention programs
      currently being implemented in military settings. Taken together, further
      research is needed to enhance the evidence base for SA prevention in the
      military, and to evaluate the effectiveness of the approaches currently being
      conducted with service members.

PMID- 29635604
TI  - Non-invasive Detection of Unique Molecular Signatures in Laser-Induced Retinal
      Injuries.
AB  - Unintentional laser exposure is an increasing concern in many operational
      environments. Determining whether a laser exposure event caused a retinal injury
      currently requires medical expertise and specialized equipment that are not
      always readily available. The purpose of this study is to test the feasibility of
      using dynamic light scattering (DLS) to non-invasively detect laser retinal
      injuries through interrogation of the vitreous humor (VH). Three grades of
      retinal laser lesions were studied: mild (minimally visible lesions), moderate
      (Grade II), and severe (Grade III). A pre-post-treatment design was used to
      collect DLS measurements in vivo at various time points, using a customized
      instrument. VH samples were analyzed by liquid chromatography/tandem mass
      spectrometry (LC-MS/MS) and relative protein abundances were determined by
      spectral counting. DLS signal analysis revealed significant changes in particle
      diameter and intensity in laser-treated groups as compared with control.
      Differences in protein profile in the VH of the laser-treated eyes were noted
      when compared with control. These results suggest that laser injury to the retina
      induces upregulation of proteins that diffuse into the VH from the damaged
      tissue, which can be detected non-invasively using DLS.

PMID- 29635605
TI  - Incident Angle Correction Algorithm For Impulse Noise Injury Assessment.
AB  - Objectives: We developed an empirical algorithm to account for the effect of the
      change in the A-weighted sound exposure level (SELA) as a result of the change in
      angle of incidence (AoI) of the impulse noise on the prediction of hearing loss.
      The product is the upgraded software tool, Auditory 4.5 that incorporates the
      incident angle correction algorithm. Methods: The SELA calculated from free-field
      pressure data is used as the dose metric that was corrected for AoI. The angle
      dependent eardrum pressure was measured by performing shock tube tests with the
      Acoustical Testing Fixture varied over a wide range of orientation angles. The
      yaw angle was varied from 0 to 360 degrees  and the pitch angle from -60 degrees 
      to +90 degrees  in 15 degrees  steps. The algorithm was constructed by
      calculating a correction factor, DeltaSELA for any given AoI at the ear relative
      to the SELA at normal incidence. The DeltaSELA values were applied to correct the
      dose values to predict injury for all AoI. Results: A three-dimensional contour
      of DeltaSELA as a function of the AoI was produced. The largest DeltaSELA was
      9.81 dB at pitch = -15 degrees  and yaw = 255 degrees . DeltaSELA values compared
      well against available benchmark data. Conclusions: A new capability has been
      incorporated in Auditory 4.5 to predict the effects of AoI on impulse noise
      injury.

PMID- 29635606
TI  - Comparison of Intubation Using Personal Protective Equipment and Standard Uniform
      in Simulated Cadaveric Models.
AB  - Introduction: The use of personal protection equipment (PPE) for patient care can
      have an impact on the delivery of effective patient care. The purpose of this
      study is to examine the effects of basic PPE on intubation times and
      corresponding success rates in cadaver models. Methods: A prospective crossover
      design using a single cohort of emergency medicine residents was used for this
      study. The primary objective is to compare time with intubation in standard
      uniform (e.g., scrubs without PPE) and using PPE. The secondary objectives are
      measuring success rates of intubation and the perceived difficulty of intubation
      when using PPE. Results: The mean time to intubation in the standard uniform
      group was 18.85 s, whereas the mean time to intubation in the PPE group was
      19.29. The overall success rate in the standard uniform group was 83% compared
      with the PPE group, which was 72%. The perceived difficulty was higher in the PPE
      group (3.38) when compared with the standard uniform. Conclusion: Although the
      mean intubation times between the groups were not significantly different, the
      overall success rate was significantly higher in the standard uniform group when
      compared with PPE group. The perceived difficulty rating was also noted to be
      significantly higher in the PPE group when compared with the standard uniform
      group.

PMID- 29635607
TI  - Retrospective Analysis of Injuries in Underbody Blast Events: 2007-2010.
AB  - Underbody Blast (UBB) exposure emerged as a substantial cause of morbidity and
      mortality of Service Members in Iraq and Afghanistan, which was unique to OIF/OEF
      due to the frequent use of improvised explosive devices. Improvised explosive
      devices under the vehicle delivered high-rate vertical loading to the vehicle
      translating energy to the occupant(s) resulting in injuries. Injury mitigating
      technologies needed to be developed; however, technologies rely on biomechanical
      human response data for research and development. Widely accepted human response
      corridors have been developed and established for slower frontal and side impact
      exposures. Currently, there are no accepted human response data for high-rate
      vertical exposures, like those experienced during UBB events. To understand the
      mechanisms and replicate the exposures, analyses of injuries caused by UBB events
      were required. Medical injury data from UBB events during OIF/OEF were examined.
      Data were categorized by disposition, body region, injury type, and severity.
      Data analyses were performed on 555 Service Members receiving a total of 3,844
      injuries. The Torso and the Head/face regions were the most injured and sustained
      predominately fractures/dislocations and internal organ injuries. This work will
      allow others to prioritize injuries to develop the methodology required to create
      response metrics to improve energy mitigating technology.

PMID- 29635608
TI  - The 2016 Military Health System Research Symposium Awards.

PMID- 29635609
TI  - Computational Modeling of Blast Wave Transmission Through Human Ear.
AB  - Hearing loss has become the most common disability among veterans. Understanding
      how blast waves propagate through the human ear is a necessary step in the
      development of effective hearing protection devices (HPDs). This article presents
      the first 3D finite element (FE) model of the human ear to simulate blast wave
      transmission through the ear. The 3D FE model of the human ear consisting of the
      ear canal, tympanic membrane, ossicular chain, and middle ear cavity was imported
      into ANSYS Workbench for coupled fluid-structure interaction analysis in the time
      domain. Blast pressure waveforms recorded external to the ear in human cadaver
      temporal bone tests were applied at the entrance of the ear canal in the model.
      The pressure waveforms near the tympanic membrane (TM) in the canal (P1) and
      behind the TM in the middle ear cavity (P2) were calculated. The model-predicted
      results were then compared with measured P1 and P2 waveforms recorded in human
      cadaver ears during blast tests. Results show that the model-derived P1 waveforms
      were in an agreement with the experimentally recorded waveforms with statistic
      Kurtosis analysis. The FE model will be used for the evaluation of HPDs in future
      studies.

PMID- 29635610
TI  - Impact of In-Person and Virtual World Mindfulness Training on Symptoms of Post
      Traumatic Stress Disorder and Attention Deficit and Hyperactivity Disorder.
AB  - Mindfulness meditation training has been shown to reduce stress and improve short
      term memory for military personnel. However, no studies have investigated the
      effects of in-person and virtual world (VW) mindfulness training on Post
      Traumatic Stress Disorder (PTSD) or Attention Deficit Hyperactivity Disorder
      (ADHD) symptoms. In this study, U.S. military active duty service members and
      veterans were pseudo-randomized into two mindfulness training groups: in-person
      (IP) and online via a VW, and a wait-list control group. Volunteers answered a
      demographic questionnaire, and completed the PTSD Checklist-Military Version (PCL
      M) and ADHD Current Symptoms Scale before and after training. The results showed
      practical and clinically relevant reductions in PTSD symptoms, particular for the
      IP group, but did not show statistical relevance with hypothesis testing. Results
      also showed post-training reductions in ADHD symptoms for both IP and VW groups,
      but no change for the control group. To investigate the effects of initial ADHD
      symptoms, IP and VW groups were combined into a single Mindfulness Training
      group. Those with high-initial ADHD symptoms attending training showed
      improvements, but the control group did not. These results expand research on the
      mindfulness training, and suggest that IP mindfulness training, rather than VW
      training, may be of greater benefit for those with PTSD symptoms, while either
      delivery system appears adequate for reducing attentional symptoms.

PMID- 29635611
TI  - Potential of Intranasal Neuropeptide Y (NPY) and/or Melanocortin 4 Receptor
      (MC4R) Antagonists for Preventing or Treating PTSD.
AB  - There is a great need for effective treatment options for post-traumatic stress
      disorder (PTSD). Neuropeptide Y (NPY) is associated with resilience to traumatic
      stress. MC4R antagonists, such as HS014, also reduce response to stress. Both
      regulate stress-responsive systems - the hypothalamic-pituitary-axis (HPA) and
      the noradrenergic nervous system and their associated behaviors. Therefore, we
      examined if their intranasal delivery to brain could attenuate development of
      PTSD-related symptoms in single prolonged stress (SPS) rodent PTSD model. Three
      regimens were used: (1) prophylactic treatment 30 min before SPS stressors, (2)
      early intervention right after SPS stressors, (3) therapeutic treatment when PTSD
      behaviors are manifested 1 wk or more after the traumatic stress. NPY delivered
      by regimen 1 or 2 prevented SPS-triggered elevation in anxiety, depressive-like
      behavior, and hyperarousal and reduced dysregulation of HPA axis. Hypothalamic
      CRH mRNA and GR in ventral hippocampus were significantly induced in vehicle- but
      not NPY-treated group. NPY also prevented hypersensitivity of LC/NE system to
      novel mild stressor and induction of CRH in amygdala. Some of these impairments
      were also reduced with HS014, alone or together with NPY. When given after
      symptoms were manifested (regiment 3), NPY attenuated anxiety and depressive
      behaviors. This demonstrates strong preclinical proof of concept for intranasal
      NPY, and perhaps MC4R antagonists, for non-invasive early pharmacological
      interventions for PTSD and comorbid disorders and possibly also as therapeutic
      strategy.

PMID- 29635612
TI  - Feasibility of Training Physical Therapists to Implement a Psychologically
      Informed Physical Therapy Program for Deployed U.S. Sailors and Marines with
      Musculoskeletal Injuries.
AB  - This study assesses the feasibility of training U.S. Navy Physical Therapy staff
      members (PT staff) aboard a U.S. Navy Aircraft Carrier in psychologically
      informed physical therapy (PiPT). Training was conducted prior to deployment over
      3 d and included background information, skills development, and application in
      the form of role playing and case studies. During deployment, nine phone
      conferences were conducted to reinforce training, assess skills, and discuss
      implementation. PiPT knowledge was assessed by a written test and role-playing
      skills. The adoption of the training was determined by analysis of clinical notes
      and verbal responses of the PT staff during phone conferences. There were two PT
      staff members on the carrier. Both received passing knowledge test scores and
      demonstrated role-playing proficiency. Clinical note assessment and discussions
      during conference calls also indicated successful implementation. The feasibility
      of training Navy PT staff to implement PiPT was demonstrated. PT staff
      successfully translated training into practice. This is significant, since PiPT
      has the potential to limit attrition due to musculoskeletal injuries in Navy
      personnel. Factors believed to be associated with the success of the training
      include adoption of the PiPT model by PT staff and reinforcement of changes in
      clinical practice during deployment.

PMID- 29635613
TI  - Using the RE-AIM Model of Health Promotion to Implement a Military Women's Health
      Promotion Program for Austere Settings.
AB  - The health concerns for military women who serve in austere environments include
      feminine hygiene, risk of infection, and limited knowledge of gynecologic
      conditions, symptoms, and prevention. The purpose of this study is to evaluate
      the effectiveness of the Women's Health Promotion Program (WHPP) for Austere
      Environments that was implemented in the military community setting of a large
      operational military unit on a southeastern U.S. military base. The WHPP is a
      pilot-tested program designed to educate women to recognize and prepare for
      environments that require alteration of feminine hygiene behaviors, with the goal
      of maintaining genitourinary health. Evaluation of the WHPP was designed
      according to the RE-AIM framework, which measures the Reach,
      Efficacy/effectiveness, Adoption, Implementation, and Maintenance of a health
      promotion program. The WHPP was offered to 49 military units (none of which
      declined) and presented to 443 military women in those units. One year after the
      implementation of the WHPP, the rates of urinary tract infections, vaginal
      candidiasis infections, and menstrual disorders decreased among the units that
      participated in the WHPP. These findings lay the foundation for an Army-wide
      adoption of this WHPP that could enhance readiness in military women.

PMID- 29635614
TI  - Army Combat Medic Resilience: The Process of Forging Loyalty.
AB  - This study presents a grounded theory analysis of in-depth interviews of United
      States Army Combat Medics (CMs) who had served in Iraq and/or Afghanistan. The
      study explores how 17 CMs nominated by their peers as resilient cope with
      military stressors in order to identify the factors that enable them to thrive
      amidst harsh conditions. Four distinct categories of characteristics unique to
      this group emerged: (1) social bonding, (2) readiness, (3) dual loyalty as
      performance, and (4) leader by example. Forging loyalty underpins these
      characteristics and represents the main process used by resilient CMs and
      comprised three behavior patterns: (1) commitment to the family, (2) commitment
      to the military mission, and (3) commitment to their guiding religious and
      spiritual beliefs. Prominent behavioral tendencies of forging loyalty likely
      developed during childhood and re-enforced by families, friends, and other role
      models. Based on the findings, new training and education efforts should focus on
      developing positive emotional, environmental, and social resources to enhance the
      health and well-being of service members and their families.

PMID- 29635615
TI  - Hydrogel Contact Lens Water Content is Dependent on Tearfilm pH.
AB  - Introduction: Based on clinical inferences, investigators theorized in situ soft
      lens hydration was linked to the precorneal tearfilm pH. Methods: Forty-one
      myopic subjects at Fort Rucker, AL, USA were fitted with one of two types of
      extended-wear soft contact lenses, and were followed quarterly for a period of 33
      mo. The anterior soft contact lens surface pH was measured in situ, while the in
      vitro lens water content was measured immediately after lens removal, using a
      hand-held refractometer on one lens, and a gravimetric means of hydration
      measurement on the other lens. Results: The in situ pH increased logarithmically
      across extended wearing time, reaching an asymptote at approximately 5 d' wearing
      time at a pH of 7.45 +/- 0.03. Lens water content was shown to similarly decrease
      at an inversely logarithmic rate, leveling off at 4-5 d' extended wearing time.
      Both means of hydration assessment correlated well with each other across days'
      extended wearing time (R = 0.98; p < 0.0001). Discussion: A log-log dual
      conversion yielded significantly different linear slopes (p < 0.001), based on a
      multifactorial analysis of both lens types, by the pH, and by their water
      content. The differing ionic status of each material accentuated their varied
      polar attraction characteristics. Two soft lenses, identical in all patient-based
      parameters, could provide differing oxygen availability, as well as differing
      physical fits in patients of identical physical characteristics, as a result of
      their unique tearfilm pH differences. Conclusion: The in situ hydrogel lens water
      content is directly dependent on the precorneal tearfilm pH.

PMID- 29635616
TI  - Issue Overview.

PMID- 29635617
TI  - Surfactant Dysfunction in ARDS and Bronchiolitis is Repaired with Cyclodextrins.
AB  - Objectives: Acute respiratory distress syndrome (ARDS) is caused by many factors
      including inhalation of toxicants, acute barotrauma, acid aspiration, and burns.
      Surfactant function is impaired in ARDS and acute airway injury resulting in high
      surface tension with alveolar and small airway collapse, edema, hypoxemia, and
      death. In this study, we explore the mechanisms whereby surfactant becomes
      dysfunctional in ARDS and bronchiolitis and its repair with a cyclodextrin drug
      that sequesters cholesterol. Methods: We used in vitro model systems, a mouse
      model of ARDS, and samples from patients with acute bronchiolitis. Surface
      tension was measured by captive bubble surfactometry. Results: Patient samples
      showed severe surfactant inhibition even in the absence of elevated cholesterol
      levels. Surfactant was also impaired in ARDS mice where the cholesterol to
      phospholipid ratio (W/W%) was increased. Methyl-beta-cyclodextrin (MbetaCD)
      restored surfactant function to normal in both human and animal samples. Model
      studies showed that the inhibition of surfactant was due to both elevated
      cholesterol and an interaction between cholesterol and oxidized phospholipids.
      MbetaCD was also shown to have anti-inflammatory effects. Conclusions: Inhaled
      cyclodextrins have potential for the treatment of ARDS. They could be delivered
      in a portable device carried in combat and used following exposure to toxic gases
      and fumes or shock secondary to hemorrhage and burns.

PMID- 29635618
TI  - Medical Device Connectivity Challenges Outline the Technical Requirements and
      Standards For Promoting Big Data Research and Personalized Medicine in
      Neurocritical Care.
AB  - Brain injuries are complicated medical problems and their management requires
      data from disparate sources to extract actionable information. In neurocritical
      care, interoperability is lacking despite the perceived benefits. Several efforts
      have been underway, but none have been widely adopted, underscoring the
      difficulty of achieving this goal. We have identified the current pain points of
      data collection and integration based on the experience with two large multi-site
      clinical studies: Transforming Research And Clinical Knowledge in Traumatic Brain
      Injury (TRACK-TBI) in the United States and Collaborative European Neuro Trauma
      Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) in Europe. The
      variability of measurements across sites remains a barrier to uniform data
      collection. We found a need for annotation standards and for a standardized
      archive format for high-resolution data. Overall, the hidden cost for successful
      data collection was initially underestimated.Although the use of bedside data
      integration solutions, such as the Moberg's Component Neuromonitoring System
      (Moberg Research, Inc., Ambler, PA, USA) or ICM+ software (Cambridge Enterprise,
      Cambridge, UK), facilitated the homogenous collection of synchronized data, there
      remain issues that need to be addressed by the neurocritical care community. To
      this end, we have organized a Working Group on Neurocritical Care Informatics,
      whose next step is to create an overarching informatics framework that takes
      advantage of the collected information to answer scientific questions and to
      accelerate the translation of trial results to actions benefitting military
      medicine.

PMID- 29635619
TI  - Ciprofloxacin and Rifampin Dual Antibiotic-Loaded Biopolymer Chitosan Sponge for
      Bacterial Inhibition.
AB  - Complex extremity wounds in Wounded Warriors can become contaminated with
      microbes, which may cause clinical outcomes resulting in amputation, morbidity,
      or even fatality. Local delivery of multiple or broad-spectrum antibiotics allows
      practicing clinicians treatment solutions that may inhibit biofilm formation.
      Propagation of vancomycin-resistant Staphylococcus aureus is also a growing
      concern. The development of vancomycin-resistant S. aureus has become a critical
      challenge in nosocomial infection prevention in the USA, but to date has seen
      little occurrence in osteomyelitis. As an alternative, locally delivered
      ciprofloxacin and rifampin were investigated in a preclinical model for the
      prevention of biofilm in complex extremity wounds with implanted fixation device.
      In vitro assays demonstrated ciprofloxacin and rifampin possess an additive
      effect against Gram-negative Pseudomonas aeruginosa and were actively eluted from
      a chitosan sponge based local delivery system. In an in vivo orthopedic hardware
      associated polymicrobial model (S. aureus and Escherichia coli) the combination
      was able to achieve complete clearance of both bacterial strains. E. coli was
      detected in bone of untreated animals, but did not form biofilm on wires. Results
      reveal the clinical potential of antibiotic-loaded chitosan sponges to inhibit
      infection through tailored antibiotic selection at desired concentrations with
      efficacy towards biofilm inhibition.

PMID- 29635620
TI  - Association of 25-OH Vitamin D Status with Findings on Screening Colonoscopy.
AB  - Objectives: Greater serum levels and dietary intake of vitamin D have been
      inversely associated with the risk of multiple cancers including colon cancer.
      Most colorectal cancers are thought to arise from adenomatous polyps, which
      become dysplastic under the influence of numerous factors. Prospective data are
      needed to distinguish between association or a causative role of vitamin D in the
      pathogenesis of colorectal cancer. Methods: A prospective cohort study was
      designed, located at a hospital-based screening colonoscopy referral center,
      including Department of Defense beneficiaries aged 18 yr or older. A serum 25
      hydroxyvitamin D level was drawn, and colonoscopy findings were recorded. A power
      calculation using p = 0.8, alpha = 0.05 generated a necessary sample size of n =
      224 to detect an association between vitamin D level and adenomatous polyp.
      Unconditional multivariable logistic regression modeling was used to evaluate
      associations between outcomes, adjusted for known risk factors. Results: Of final
      population (n) = 228, 155 (68%) were diagnosed with vitamin D insufficiency (<30
      ng/mL) and 104 (46%) were found to have adenomatous polyps. Adjusted odds ratio
      for adenomatous colon polyp given vitamin D <30 ng/mL = 1.16 (95% CI 0.57-2.36).
      Conclusions: Serum vitamin D level was not associated with increased adenomatous
      polyp detection at screening colonoscopy in this population.

PMID- 29635621
TI  - Deployment Anxiety Reduction Training: A Pilot Study of Acceptability and
      Feasibility in Current or Recent Active Duty Service Members.
AB  - Objectives: The Deployment Anxiety Reduction Training (DART) is a manualized tool
      that was developed and piloted with active duty service members and recently
      deployed veterans regarding their response to potential and experienced acute
      combat stress reactions. DART is low risk and has high potential to be
      beneficial. It is a brief, one-session, non-pharmacological approach designed to
      reduce symptoms of peritraumatic panic and increase resilience in the face of a
      potentially traumatic stressor. Methods: This study was a mixed-methods pilot
      study to assess the utility and acceptability of DART during deployment. Results:
      Self-report and interview responses indicated that participants generally found
      the DART techniques acceptable and easy to understand. Overall, the techniques
      were perceived as likely to be helpful with high utility, although there was
      variation in perceived helpfulness among the different techniques. Participants
      overwhelmingly positively endorsed delivery of the DART protocol through use of
      smartphone technology. Conclusions: Results indicate that the DART components
      were considered highly acceptable and feasible for use in the deployed
      environment.

PMID- 29635622
TI  - Local Delivery of Amikacin and Vancomycin from Chitosan Sponges Prevent
      Polymicrobial Implant-Associated Biofilm.
AB  - Military personnel have high risk for infection, particularly those with combat
      related extremity trauma. Administration of multiple or broad-spectrum
      antibiotics provides clinicians with a strategy for preventing biofilm-based
      medical device infections. Selection of effective antibiotic combinations based
      on common pathogens may be used to improve chitosan wound dressing sponge-based
      local antibiotic delivery systems. In vitro assays in this study demonstrate that
      vancomycin and amikacin have a synergistic relationship against a strain of
      osteomyelitis-producing Gram-positive Staphylococcus aureus, although an
      indifferent relationship was observed against Gram-negative Pseudomonas
      aeruginosa. In an in vivo model of orthopedic hardware-associated polymicrobial
      (S. aureus and Escherichia coli) biofilm, chitosan sponges loaded with a
      combination of vancomycin and amikacin at 5 mg/mL each showed a greater
      percentage of complete clearance, 50%, than either antibiotic alone, 8.33%.
      Doubling the loading concentration of the combination achieved a complete
      clearance rate of 100%, a four log-fold reduction of S. aureus on the wire and a
      six log-fold reduction in bone. E. coli was detected in bone of untreated animals
      but did not form biofilm on wires. Results demonstrate the clinical potential of
      chitosan sponges to prevent infection and illustrates antibiotic selection and
      loading concentrations necessary for effective biofilm prevention.

PMID- 29635623
TI  - Inertial Sensor-Based Assessment of Central Sensory Integration for Balance After
      Mild Traumatic Brain Injury.
AB  - Introduction: Optimal balance control requires a complex integration of sensory
      information from the visual, vestibular, and proprioceptive systems. The goal of
      this study is to determine if the instrumented modified Clinical Test of Sensory
      Integration and Balance (mCTSIB) was impaired acutely after mild traumatic brain
      injury (mTBI) when postural sway under varying sensory conditions was measured
      with a wearable inertial sensor. Materials and Methods: Postural sway was
      assessed in athletes who had sustained a mTBI within the past 2-3 d (n = 38) and
      control athletes (n = 81). Postural sway was quantified with a wearable inertial
      sensor (Opal; APDM, Inc.) during four varying sensory conditions of quiet stance:
      (1) eyes open (EO) firm surface, (2) eyes closed (EC) firm surface, (3) eyes open
      (EO) foam surface, and (4) eyes closed (EC) foam surface. Sensory reweighting
      deficits were computed by comparing the postural sway area in eyes closed versus
      eyes open conditions for firm and foam condition. Results: Postural sway was
      higher for mTBI compared with the control group during three of the four
      conditions of instrumented mCTSIB (EO firm, EC firm, and EC foam; p < 0.05).
      Sensory reweighting deficits were evident for mTBI individuals compared with
      control group on foam surface (EC firm vs EO firm; p < 0.05) and not on firm
      surface (EC firm vs EO firm; p = 0.63). Conclusions: The results from this study
      highlight the importance of detecting postural sway deficits during sensorimotor
      integration in mild TBI individuals.

PMID- 29635624
TI  - An Innovative Advance in Non-invasive Wound Closure: A New Paradigm.
AB  - Injury is the leading health and readiness threat to the armed forces, with two
      million instances per year; therefore, innovating wound care solutions can help
      improve readiness. The DermaClip Skin Closure Device is a new, non-invasive,
      painless, and easy-to-apply wound closure device that does not require either
      needles or painful anesthesia injections or create additional damage to the
      wounded area. The efficacy of the device was tested in a 120-patient trial,
      composed of 60 experimental cases and 60 control cases. The trial of the
      DermaClip device demonstrated the device's efficacy in meeting the needs of
      clinical applications. Additionally, the experimental group had no adverse events
      in the product safety test. The efficacy of the device coupled with the features
      of ease of use and limited requirements for application make this a wound closure
      device particularly applicable to the emergency and battlefield setting.

PMID- 29635625
TI  - Ocular Manifestations of Mosquito-Transmitted Diseases.
AB  - Of the 3,548 known mosquito species, about 100 transmit human diseases.
      Mosquitoes are distributed globally throughout tropical and temperate regions
      where standing water sources are available for egg laying and the maturation of
      larva. Female mosquitoes require blood meals for egg production. This is the main
      pathway for disease transmission. Mosquitoes carry several pathogenic organisms
      responsible for significant ocular pathology and vision loss including West Nile,
      Rift Valley, chikungunya, dengue viruses, various encephalitis viruses, malarial
      parasites, Francisella tularensis, microfilarial parasites, including
      Dirofilaria, Wuchereria, and Brugia spp., and human botfly larvae. Health care
      providers may not be familiar with many of these mosquito-transmitted diseases or
      their associated ocular findings delaying diagnosis, treatment, and recovery of
      visual function. This article aims to provide an overview of the ocular
      manifestations associated with mosquito-transmitted diseases.

PMID- 29635626
TI  - Exosomal microRNAs in seminal plasma are markers of the origin of azoospermia and
      can predict the presence of sperm in testicular tissue.
AB  - STUDY QUESTION: Are exosomal microRNAs (miRNAs) in seminal plasma (SP) useful as
      markers of the origin of azoospermia and the presence of sperm in the testis?
      SUMMARY ANSWER: Our study demonstrated the potential of several miRNAs contained
      in small extracellular vesicles (sEVs) of seminal fluid as sensitive and specific
      biomarkers for selecting those azoospermic individuals with real chances of
      obtaining spermatozoa from the testicular biopsy. WHAT IS KNOWN ALREADY: There
      are no precise non-invasive diagnostic methods for classifying the origin of the
      sperm defects in semen and the spermatogenic reserve of the testis in those
      infertile men with a total absence of sperm in the ejaculate (azoospermia). The
      diagnosis of such individuals is often based on the practice of biopsies. In this
      context it is reasonable to study the presence of organ-specific markers in human
      semen that contains fluid from the testis and the male reproductive glands, which
      could help in the diagnosis and prognosis of male infertility. Additionally,
      seminal fluid contains high concentrations of sEVs that are morphologically and
      molecularly consistent with exosomes, which originate from multiple cellular
      sources in the male reproductive tract. STUDY DESIGN, SIZE, DURATION: A case and
      control prospective study was performed. This study compares the miRNA content of
      exosomes in semen samples obtained from nine normozoospermic fertile individuals
      (control group), 14 infertile men diagnosed with azoospermia due to spermatogenic
      failure, and 13 individuals with obstructive azoospermia and conserved
      spermatogenesis. Additionally, three severe oligozoospermic individuals (<5 * 106
      sperm/ml) were included in the study. PARTICIPANTS/MATERIALS, SETTING, METHODS: A
      differential high-throughput miRNA profiling analysis using miRNA quantitative
      PCR panels was performed in SP exosomes from azoospermic patients and fertile
      individuals. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 623 miRNAs were
      included in the miRNA profiling stage of the study. A total of 397 miRNAs (63.7%)
      were consistently detected in samples from all groups and statistically analysed,
      which revealed altered patterns of miRNA expression in infertile patients. We
      focused on the miRNAs that were differentially expressed between azoospermia as a
      result of an obstruction in the genital tract (i.e. having conserved
      spermatogenesis) and azoospermia caused by spermatogenic failure, and described,
      in a miRNA validation stage of the study, the expression values of one miRNA (miR
      31-5p) in exosomes from semen as a predictive biomarker test for the origin of
      azoospermia with high sensitivity and specificity (>90%). The efficacy of the
      predictive test was even better when the blood FSH values were included in the
      analysis. Furthermore a model that included miR-539-5p and miR-941 expression
      values is also described as being useful for predicting the presence of residual
      spermatogenesis in individuals with severe spermatogenic disorders with
      diagnostic accuracy. LIMITATIONS, REASONS FOR CAUTION: Further studies, with an
      independent second population involving a larger number of samples, are needed to
      confirm our findings. WIDER IMPLICATIONS OF THE FINDINGS: Our findings contribute
      to the search for the most valuable genetic markers that are potentially useful
      as tools for predicting the presence of testicular sperm in azoospermic
      individuals. STUDY FUNDING/COMPETING INTEREST(S): This work was financially
      supported by grants from the Fondo de Investigaciones Sanitarias/Fondo Europeo de
      Desarrollo Regional "Una manera de hacer Europa" (FIS/FEDER) [Grant number
      PI15/00153], the Generalitat de Catalunya [Grant number 2014SGR5412]. S.L. is
      sponsored by the Researchers Stabilization Program (ISCIII/Generalitat de
      Catalunya) from the Spanish National Health System [CES09/020].

PMID- 29635628
TI  - Outstanding Merit Award for 2017.

PMID- 29635627
TI  - An exclusion criterion for acute pericarditis.

PMID- 29635629
TI  - Temocillin against Enterobacteriaceae isolates from community-acquired urinary
      tract infections: low rate of resistance and good accuracy of routine
      susceptibility testing methods.
AB  - Background: Temocillin is an old 'revived' antibiotic that may play an important
      role in the treatment of febrile urinary tract infection (UTI). Data regarding
      its activity against current Enterobacteriaceae isolates as well as the
      performance of routine susceptibility testing methods are, however, scarce.
      Objectives: To determine the MICs of temocillin for Enterobacteriaceae strains
      reflecting the current epidemiology and to analyse the accuracy of three
      commercial methods. Methods: Enterobacteriaceae isolates causing community
      acquired UTI were prospectively collected from September 2015 to January 2017 in
      two French centres. Temocillin MIC was determined by agar dilution (AD) as the
      reference method and then compared with: (i) susceptibility testing by disc
      diffusion; (ii) MIC determination by Etest; and (iii) MIC estimation by the Vitek
      2 automated system. Results: A total of 762 Enterobacteriaceae were analysed
      comprising 658 (86.4%) Escherichia coli and 37 (4.9%) ESBL-producing isolates.
      Susceptibility rate assessed by AD was 99.6% according to the 8 mg/L clinical
      breakpoint and was significantly lower against the ESBL-producing isolates than
      the non-ESBL-producing isolates (94.6% versus 99.9%, P < 0.01). The MIC50 and
      MIC90 for the total set were 3 and 6 mg/L, respectively. According to the 8 mg/L
      clinical breakpoint, the major error rate was <1% for disc diffusion and Etest,
      and significantly higher for Vitek 2 (4.3%, P < 0.01), but still low. No very
      major error was noticed. Conclusions: Temocillin showed a high level of activity
      against Enterobacteriaceae from community-acquired UTI and good to excellent
      reliability of routine methods for susceptibility testing in such a setting.

PMID- 29635631
TI  - Trend Analysis of Current Modalities for Monitoring Fluid Therapy in Patients
      With Large Burns: Echoing the Call for Better Resuscitation Indices.
AB  - The aim of this study was to investigate whether current standards at our
      institution have effectively monitored resuscitations of severely burned patients
      during the first 48 hours postburn. Demographics, injuries assessed by TBSA and
      full thickness (FT), and resuscitation volumes (lactated Ringer's [LR]) were
      compared for all patients and those who died or survived. Means and standard
      deviations of hourly indices (urinary output [UOP], lactate [LAC], base excess
      [BE]) vs LR were analyzed. Waveforms, four-quadrant concordance, and correlation
      were also employed to compare the trending abilities (hourly changes [?]) of
      aforementioned variables vs LR. A total of 203 patients were included in the
      analysis. Of these patients, 71 (35%) died, and 50 (25%) had inhalation injuries.
      Mean age and weight were 47 +/- 19 years and 87 +/- 18 kg, respectively. Mean
      TBSA burned was 41 +/- 20%, with a mean FT of 18 +/- 24%. Importantly, normalized
      waveform plots demonstrated the inability of UO, LAC, and BE to follow hourly
      changes in LR. Correlation of these variables was weak (r>>-1). This was
      confirmed by concordance plots. Slopes in all groups demonstrated that UOP was a
      better resuscitative monitor than LAC or BE. ?UOP responded to ?LR better in
      patients who survived than died. Reliance on hourly UOP as the sole index of
      optimal resuscitation is not supported. This study echoed the call for better
      resuscitation indices.

PMID- 29635630
TI  - Creatine enhances the duration of sperm capacitation: a novel factor for
      improving in vitro fertilization with small numbers of sperm.
AB  - STUDY QUESTION: Why are many sperm required for successful fertilization of
      oocytes in vitro, even though fertilization occurs in vivo when only a few sperm
      reach the oocyte? SUMMARY ANSWER: Creatine produced in the ovary promotes
      efficient fertilization in vivo; however, in vitro, creatine is not contained in
      the in vitro fertilization (IVF) medium. WHAT IS KNOWN ALREADY: The IVF medium
      enables capacitation of sperm. However, the IVF medium does not fully mimic the
      in vivo environment during fertilization. Consequently, fertilization in vitro is
      more inefficient than in the oviduct. STUDY DESIGN, SIZE, DURATION: Follicular
      and oviductal fluids were collected and then analyzed for creatine and glucose
      levels. To determine the physiological functions of creatine, the creatine
      antagonist 3-guanidinopropionic acid (GPA) was injected into hormonally primed
      mice. Using conventional IVF protocols, sperm were pre-incubated in IVF medium
      with creatine and then co-cultured with 10 ovulated cumulus-oocyte complexes (1
      1000 per oocyte) in 50 MUl medium droplets. PARTICIPANTS/MATERIALS, SETTING,
      METHODS: Glucose and creatine levels were measured using commercial enzymatic
      assay kits. The effect of creatine in vivo was assessed by mating experiments
      using mice treated with or without GPA just before ovulation. To assess the
      functions of sperm incubated in IVF medium containing creatine, we analyzed (1)
      the motility of sperm using computer-assisted sperm assay, (2) the capacitation
      level of sperm by western blot analyses, and (3) the condition of sperm acrosomes
      by peanut agglutinin lectin-FITC staining. MAIN RESULTS AND THE ROLE OF CHANCE:
      Oviductal creatine levels were significantly increased following ovulation.
      Injecting mice with GPA just before ovulation significantly reduced the number of
      fertilized oocytes. The addition of creatine to IVF medium enhanced sperm
      capacitation by increasing ATP levels. Successful fertilization was achieved with
      as few as five sperm/oocyte in the creatine group, and the number of fertilized
      oocytes was significantly higher than in the control without creatine (P < 0.01).
      LIMITATIONS, REASONS FOR CAUTION: In the present study, a pharmacological
      approach, creatine antagonist (GPA) treatment, but not a knockout mouse model,
      was used to understand the role of creatine in vivo. The role of creatine in
      fertilization processes can only be shown in a mouse model. WIDER IMPLICATIONS OF
      THE FINDINGS: A modified IVF technique using creatine-containing medium was
      developed and shown to markedly improve fertilization with small numbers of
      sperm. This approach has the potential to be highly beneficial for human assisted
      reproductive technologies, especially for patients with a limited number of good
      quality sperm. STUDY FUNDING/COMPETING INTEREST(S): This work was supported in
      part by JSPS KAKENHI Grant numbers JP24688028, JP16H05017 (to M.S.), and
      JP15J05331 (to T.U.), the Japan Agency for Medical Research and Development
      (AMED) (16gk0110015h0001 to M.S.), and National Institutes of Health (NIH-HD
      076980 to J.S.R). The authors have nothing to disclose.

PMID- 29635632
TI  - A double-blind, randomized comparative study to investigate the morphine to
      hydromorphone conversion ratio in Japanese cancer patients.
AB  - Objective: To confirm the morphine to hydromorphone conversion ratio for
      hydromorphone (DS-7113b) immediate-release tablets in cancer patients who
      achieved pain control with oral morphine. Methods: This was a multicenter, active
      controlled, randomized, double-blind, parallel-group, comparative study (July
      2013 to December 2014) at 39 Japanese sites. Seventy-one patients (aged >20
      years) who had achieved pain control with morphine 60 mg/day and 90 mg/day were
      randomly allocated 1:1 to hydromorphone immediate-release tablets at a dose
      converted at a hydromorphone:morphine ratio of 1:5 or 1:8, respectively, and
      treated for up to 5 days. The efficacy was evaluated as the pain control ratio.
      Results: The pain control ratio in the full analysis set was 83.3% (25/30) in the
      conversion ratio 1:5 group and 95.0% (38/40) in the conversion ratio 1:8 group,
      and both groups demonstrated highly successful pain control. The incidence of
      adverse events was 46.7% (14/30) in the conversion ratio 1:5 group and 58.5%
      (24/41) in the 1:8 group; the difference was not clinically relevant. Frequently
      observed adverse events (incidence >=5%) were nausea, vomiting, diarrhea,
      somnolence and dyspnea. Conclusions: A high pain control ratio was maintained by
      a switch at either conversion ratio, and no notable difference was observed in
      the incidence of adverse events. A switch from morphine to hydromorphone is
      effective at a dose converted at ratios of 1:5 and 1:8.

PMID- 29635633
TI  - Genetic parameters for fecal egg counts and their relationship with body weights
      in Katahdin lambs.
AB  - Reliance on anthelmintic drugs to control internal parasites in sheep is no
      longer sustainable because of the development of resistance to these drugs in
      parasite populations. Genetic selection may offer an alternative long-term
      solution, as differences in parasite resistance exist both within and among sheep
      breeds. However, selection for parasite resistance may have correlated effects on
      other production traits. The objectives of this study were to estimate genetic
      parameters for weaning (WFEC) and postweaning (PWFEC) fecal egg counts (FEC) and
      assess their relationship with birth (BWT), weaning (WWT), and postweaning (PWWT)
      BW in Katahdin lambs. The study used WFEC (n = 2,537), PWFEC (n = 3.421), BWT (n
      = 12,869), WWT (n = 10,961), and PWWT (n = 7,812) from 12,869 lambs measured
      between 2003 and 2015 in 13 flocks enrolled in the U.S. National Sheep
      Improvement Program. Animal and sire models were fitted to the data using the
      ASReml statistical package. Records were corrected for fixed effects of dam age,
      joint effect of type of birth and rearing, and management group (defined by joint
      effects of flock, sex, and birth year and season); lamb age in days at each
      measurement time was fitted as a covariate. Maternal additive and maternal
      permanent environmental effects were not significant (P > 0.05), but litter
      effects influenced (P < 0.01) both WFEC and PWFEC. Heritability estimates ranged
      from 0.18 to 0.26 for WFEC and 0.23 to 0.46 for PWFEC, depending on the model
      used. Heritability estimates from sire models were higher than estimates from
      animal models. Direct additive, litter, residual, and phenotypic correlations
      between WFEC and PWFEC were 0.82, 0.25, 0.15, and 0.29, respectively. Bivariate
      analyses revealed low to moderate correlations between BW and FEC. Moderate
      heritabilities for FEC in this study indicated that genetic progress for this
      trait can be achieved in Katahdin lambs and that selection for low FEC should
      have little or no effect on BW.

PMID- 29635634
TI  - Phosphofructokinase and mitochondria partially explain the high ultimate pH of
      broiler pectoralis major muscle.
AB  - During postmortem metabolism, muscle pH gradually declines to reach an ultimate
      pH near 5.6 across most meat species. Yet, broiler pectoralis major (P. major)
      muscle generates meat with high ultimate pH (pH ~ 5.9). For better understanding
      of the underlying mechanism responsible for this phenomenon, we evaluated the
      involvement of breast muscle chilling on the extent of postmortem metabolism.
      Broiler breast muscles were either subjected to chilling treatment (control) or
      left at room temperature (RT) for 120 min. P. major muscle from the RT treatment
      had lower ultimate pH, greater glycogen degradation and lactate accumulation.
      While these findings suggest that carcass chilling can contribute to the
      premature termination of postmortem metabolism, chilling did not fully explain
      the high ultimate pH of P. major muscle. Our results also revealed that glucose-6
      phosphate (G6P) was very low at 24 h, and therefore we hypothesized that G6P was
      limiting. To test this hypothesis, muscle samples from P. major and porcine
      longissimus lumborum (LL) muscle were homogenized into a reaction buffer that
      mimics postmortem glycolysis with or without 0.5 mg/mL isolated mitochondria.
      While samples containing porcine LL muscle reached the normal level of ultimate
      pH, P. major muscle samples reached a value similar to that observed in vivo even
      in the presence of excess G6P, indicating that G6P was not limiting. Mitochondria
      enhanced the glycolytic flux and pH decline in systems containing muscle from
      both species. More importantly, however, was that in vitro system containing
      chicken with mitochondria reached pH value similar to that of samples containing
      LL muscle without mitochondria. To investigate further, phosphofructokinase (PFK)
      activity was compared in broiler P. major and porcine LL muscle at different pH
      values. PFK activity was lower in P. major muscle at pH 7, 6.5, and 6.2 than LL
      muscle. In conclusion, carcass chilling can partially contribute to the high
      ultimate pH of broiler P. major muscle, while low PFK activity and mitochondria
      content limit the flux through glycolysis.

PMID- 29635635
TI  - A Healthy Eating Identity is Associated with Healthier Food Choice Behaviors
      Among U.S. Army Soldiers.
AB  - Introduction: Promoting healthy eating among Soldiers is a priority to the Army
      due to the link between nutrition and performance. The Army typically uses
      nutrition education to encourage Soldiers to make healthier food choices with low
      emphasis on other psychosocial determinants of food choice behaviors. Materials
      and Methods: Drill Sergeant Candidates (n = 575) completed surveys assessing
      nutrition knowledge, eating identity type, and food choice behaviors including
      fruit and vegetable intake, skipping meals, and eating out frequency. In multiple
      linear regression models using full-information maximum likelihood estimation
      while controlling for race/ethnicity, education, and marital status, we examined
      relationships between nutrition knowledge, a healthy eating identity, and
      Soldiers' food choice behaviors. The study was approved by the Department of
      Defense and University of South Carolina's Institutional Review Boards. Results:
      A healthy eating identity was positively associated with greater fruit and
      vegetable consumption (p < 0.05), and negatively associated with skipping meals
      and eating out frequency (p < 0.05). Nutrition knowledge was negatively
      associated with skipping meals (p < 0.05). Conclusions: Findings suggest that
      fostering a healthy eating identity may be more effective for promoting healthy
      food choice behaviors than nutrition education alone. Determining if various
      points in a Soldier's career could be leveraged to influence a healthy eating
      identity and behaviors could be an important strategy to improve compliance with
      health promotion programs.

PMID- 29635636
TI  - Electric shielding films for biased TEM samples and their application to in situ
      electron holography.
AB  - We developed a novel sample preparation method for transmission electron
      microscopy (TEM) to suppress superfluous electric fields leaked from biased TEM
      samples. In this method, a thin TEM sample is first coated with an insulating
      amorphous aluminum oxide (AlOx) film with a thickness of about 20 nm. Then, the
      sample is coated with a conductive amorphous carbon film with a thickness of
      about 10 nm, and the film is grounded. This technique was applied to a model
      sample of a metal electrode/Li-ion-conductive-solid-electrolyte/metal electrode
      for biasing electron holography. We found that AlOx film with a thickness of 10
      nm has a large withstand voltage of about 8 V and that double layers of AlOx and
      carbon act as a 'nano-shield' to suppress 99% of the electric fields outside of
      the sample. We also found an asymmetry potential distribution between high and
      low potential electrodes in biased solid-electrolyte, indicating different
      accumulation behaviors of lithium-ions (Li+) and lithium-ion vacancies (VLi-) in
      the biased solid-electrolyte.

PMID- 29635637
TI  - Are We Delivering Optimal Pulmonary Rehabilitation? The Importance of Quality
      Indicators in Evaluating Clinical Practice.
AB  - Pulmonary rehabilitation (PR) is a complex intervention that has been shown to
      improve exercise capacity and quality of life, reduce dyspnea, and decrease the
      risk of exacerbations and hospitalization. Although the evidence for PR is
      strong, the translation of this evidence into clinical practice remains a
      challenge, and important gaps in care exist. To date, most research in PR has
      focused on questions related to treatment efficacy. Less attention has been paid
      to confirming whether the strong evidence base of PR has been effectively
      translated to this complex clinical setting. Policy makers and other stakeholders
      in PR are calling for the establishment of core standards and quality indicators
      in PR to evaluate existing programs and improve patient care. However, what are
      quality indicators, and how are they used? This Perspective explores quality
      assurance in the context of PR and introduces the concepts and uses of quality
      indicators that can be used to evaluate and improve the quality of care.

PMID- 29635639
TI  - Subcutaneous tocilizumab in rheumatoid arthritis: findings from the common
      framework phase 4 study programme TOZURA conducted in 22 countries.

PMID- 29635638
TI  - Enhanced detection of microsatellite instability using pre-PCR elimination of
      wild-type DNA homo-polymers in tissue and liquid biopsies.
AB  - Detection of microsatellite-instability in colonoscopy-obtained polyps, as well
      as in plasma-circulating DNA, is frequently confounded by sensitivity issues due
      to co-existing excessive amounts of wild-type DNA. While also an issue for point
      mutations, this is particularly problematic for microsatellite changes, due to
      the high false-positive artifacts generated by polymerase slippage (stutter
      bands). Here, we describe a nuclease-based approach, NaME-PrO, that uses
      overlapping oligonucleotides to eliminate unaltered micro-satellites at the
      genomic DNA level, prior to PCR. By appropriate design of the overlapping
      oligonucleotides, NaME-PrO eliminates WT alleles in long single-base homopolymers
      ranging from 10 to 27 nucleotides in length, while sparing targets containing
      variable-length indels at any position within the homopolymer. We evaluated 5 MSI
      targets individually or simultaneously, NR27, NR21, NR24, BAT25 and BAT26 using
      DNA from cell-lines, biopsies and circulating-DNA from colorectal cancer
      patients. NaME-PrO enriched altered microsatellites and detected alterations down
      to 0.01% allelic-frequency using high-resolution-melting, improving detection
      sensitivity by 500-1000-fold relative to current HRM approaches. Capillary
      electrophoresis also demonstrated enhanced sensitivity and enrichment of indels 1
      16 bases long. We anticipate application of this highly-multiplex-able method
      either with standard 5-plex reactions in conjunction with HRM/capillary
      electrophoresis or massively-parallel-sequencing-based detection of MSI on
      numerous targets for sensitive MSI-detection.

PMID- 29635640
TI  - Reply to comment "Do prebiotics reduce the risk of travelers' diarrhea? Promising
      but more research needed".

PMID- 29635641
TI  - Travel and biologic therapy: travel-related infection risk, vaccine response and
      recommendations.
AB  - Background: Biologic therapy has revolutionized the management of refractory
      chronic autoimmune and auto-inflammatory disease, as well as several
      malignancies, providing rapid symptomatic relief and/or disease remission.
      Patients receiving biologic therapies have an improved quality of life,
      facilitating travel to exotic destinations and potentially placing them at risk
      of a range of infections. For each biologic agent, we review associated travel
      related infection risk and expected travel vaccine response and effectiveness.
      Methods: A PUBMED search [vaccination OR vaccine] AND/OR ['specific vaccine']
      AND/OR [immunology OR immune response OR response] AND [biologic OR biological OR
      biologic agent] was performed. A review of the literature was performed in order
      to develop recommendations on vaccination for patients in receipt of biologic
      therapy travelling to high-risk travel destinations. Results: There is a paucity
      of literature in this area, however, it is apparent that travel-related infection
      risk is increased in patients on biologic therapy and when illness occurs they
      are at a higher risk of complication and hospitalization. Patients in receipt of
      biologic agents are deemed as having a high level of immunosuppression-live
      vaccines, including the yellow fever vaccine, are contraindicated. Inactivated
      vaccines are considered safe; however, vaccine response can be attenuated by the
      patient's biologic therapy, thereby resulting in reduced vaccine effectiveness
      and protection. Conclusions: Best practice requires a collaborative approach
      between the patient's primary healthcare physician, relevant specialist and
      travel medicine expert, who should all be familiar with the immunosuppressive and
      immunomodulatory effects resulting from the biologic therapies. Timing of
      vaccines should be carefully planned, and if possible, vaccination provided well
      before established immunosuppression.

PMID- 29635642
TI  - An analysis of international traveller deaths at the Cliffs of Moher in Ireland,
      1993-2017.
AB  - Background: Traumatic deaths, and more particularly suicides, during
      international travel receive a disproportionately low level of attention in the
      travel medicine literature. We describe the demographic profile of international
      travellers whose death occurred at the Cliffs of Moher along the Atlantic
      seaboard in Ireland. Methods: Coroners' files for the 25 years between 1993 and
      2017 were interrogated. All cases of death on or at the cliffs were examined, and
      demographic data were extracted, including date of death, gender, age,
      nationality, whether the victims were alone at the cliffs prior to their death,
      whether the fall was witnessed, prevailing weather conditions, post-mortem
      examinations, toxicology reports and inquest verdicts. Results: Overall, 66
      deaths occurred on or at the base of the Cliffs of Moher during the period 1993
      through August 2017. In total, 18 (27.3%) of the victims were international
      visitors to Ireland, including 11 males (61.1%). The mean age of travellers (n =
      17) was 34.2 years. Victims were nationals of 12 different countries, with 13
      being European nationals. Most deaths occurred in summer (n = 7) or spring (n =
      6), with eight deaths (44%) reported at weekends. In total, 15 victims (83.3%)
      had walked along the cliff path alone. A jump or fall from the cliffs was
      witnessed in only two cases (11.1%). Post-mortem examinations revealed multiple
      traumatic injuries consistent with a fall from a height. Four cases had evidence
      of alcohol intoxication. Suicide or open verdicts were returned in 50% (n = 9) of
      the cases. Conclusions: Travelling alone to the site, purchasing one-way tickets,
      or depositing belongings on the clifftop support the possibility of suicidal
      intent, while being intoxicated could be a co-factor in suicidal jumps or support
      the possibility of an accidental fall. This knowledge could help to identify
      travellers at the greatest risk of death at cliffs.

PMID- 29635643
TI  - LTBI among migrants by Mediterranean Sea: assessing prevalence and its variations
      according with different thresholds and diagnostic tools. A 10-month on-field
      experience.
AB  - Background: In 2016, 362 753 migrants reached Europe by sea. Most of migrants
      come from high tuberculosis (TB) burden countries and travel in conditions that
      increase the risk for communicable diseases. The goal of WHO End TB Strategy is
      to end global epidemic by 2035. Management of latent TB infection (LTBI) in low
      TB incidence countries is thus essential. Nevertheless, a lack of uniformity in
      policies and procedures for LTBI screening in Europe is perceived. The aim of
      this study was to estimate the LTBI prevalence in migrants by Mediterranean Sea.
      Methods: A cross-sectional study was conducted, involving 1038 migrants. Since a
      gold standard method is not available, LTBI prevalence was assessed in four
      alternative scenarios with different thresholds and diagnostic tools: (i) TST >=
      5 mm; (ii) TST >= 10 mm; (iii) TST >= 5 mm plus IGRA; and (iv) TST >= 10 mm plus
      IGRA. TST = tuberculin skin test; IGRA = interferon-gamma release assay. Results:
      The four scenarios returned the following prevalence: (i) TST >= 5 mm: 40%; (ii)
      TST >= 10 mm: 33%; (iii) TST >= 5 mm plus IGRA: 27%; and (iv) TST >= 10 mm plus
      IGRA: 25%. Moreover, a positive association was found between the proportion of
      IGRA positive patients and the size of TST induration site. No patient who
      reported TST >= 18 mm tested IGRA negative. Conclusions: Prevalence varied
      substantially in the investigated scenarios. Significant differences were noted
      according with the nationality of migrants, probably attributable to different
      Bacillus Calmette-Guerin vaccination coverage rates in the countries of origin or
      different exposition to non-tuberculous mycobacteria infection. Data about the
      nationality can suggest the need of a tailored approach according to migrants'
      area of origin.

PMID- 29635644
TI  - Recommendations for travellers during the yellow fever outbreaks in Brazil-2018.

PMID- 29635645
TI  - Acute kidney injury changes with the seasons.

PMID- 29635646
TI  - Developmental Exposure to Aluminum Chloride Irreversibly Affects Postnatal
      Hippocampal Neurogenesis Involving Multiple Functions in Mice.
AB  - Aluminum (Al) is neurotoxic to adults and also to infants. In this study, we
      investigated the developmental exposure effect of AlCl3 on postnatal hippocampal
      neurogenesis. Pregnant mice were administered 0-, 900-, or 1800-ppm AlCl3 via
      drinking water from gestational day 6 to postnatal day (PND) 21, with their
      offspring examined on PND 21 and PND 77. On PND 21, GFAP-immunoreactive (+)
      neural stem cells (NSCs) and p21Cip1/Waf1+ cells were decreased in number in the
      subgranular zone at 900 and >=900 ppm, respectively. Pcna transcript level
      examined at 1800 ppm was decreased in the dentate gyrus. These results suggest
      induction of compromised cell quiescence that caused impaired self-renewal
      capacity of NSCs accompanying slowing down of cell cycling, which ultimately
      resulted in exhaustion of the NSC pool. At 1800 ppm, Reelin+ hilar GABAergic
      interneurons were also decreased, suggesting a contribution to the NSC reduction.
      At this dose, TBR2+ or DCX+ progenitor and immature granule cells and PVALB+
      interneurons were increased. Moreover, COX-2+ granule cells were increased at
      >=900 ppm. These results suggest facilitation of transient progenitor cell
      proliferation and differentiation during exposure. Moreover, TUNEL+ or Morin
      stained granule cells were increased, together with Casp12 transcript
      upregulation, suggesting induction of Al accumulation-related endoplasmic
      reticulum stress-mediated granule cell apoptosis. Transcript expression changes
      on cholinergic and glutamatergic signals and synaptic plasticity suggested
      contribution to disruptive neurogenesis. The NSC-targeting effects sustained
      through the adult stage despite no sustained Al-accumulation. These results
      suggest that developmental AlCl3-exposure irreversibly affects postnatal
      hippocampal neurogenesis involving multiple functions in mice.

PMID- 29635647
TI  - Tension Band Wire Fixation Technique for Anterior Cruciate Ligament Tibial
      Avulsion Fracture: A New Fixation Technique.
AB  - This study evaluated clinical results of tension band wire fixation technique in
      the arthroscopic treatment of anterior cruciate ligament (ACL) tibial avulsion
      fracture. This study included 148 cases of ACL tibial avulsion fracture treated
      using arthroscopic tension band wire fixation technique. Patients were followed
      up for 25 to 36 months with an average of 27 months and evaluated in accordance
      with the International Knee Documentation Committee (IKDC) and Lysholm knee
      scoring scale. Fractures were united within 3 months after surgery in all cases.
      During the last follow-up, the anterior drawer, Lachman, and pivot shift tests
      showed negative, except for eight patients who had a 1-degree positive anterior
      drawer test. KT-1000 knee stability test showed no anterior instability exceeding
      2 mm in 132 patients and 4 mm in 8 patients. In accordance with the IKDC scale,
      the knees of 132 patients were graded normal, whereas 8 other patients were
      nearly normal. Lysholm scores before surgery and during the last follow-up were
      72.4 +/- 3.2 and 97.5 +/- 2.2, respectively. Statistically significant
      differences were observed among the Lysholm scores (p < 0.05). The Tegner scores
      were 6.5 +/- 0.9 before injury and 6.4 +/- 0.7 at the last follow-up (p > 0.05).
      No statistically significant differences between the preinjury and postoperative
      activity level were observed. All patients were satisfied with the outcomes of
      operation. Arthroscopic treatment of ACL tibial avulsion fracture by using
      tension band wire fixation technique ensures fracture healing and restores the
      stability and function of the joint in most patients. The level of evidence for
      this study is III.

PMID- 29635648
TI  - Ten-Year Results of the Press Fit Condylar Sigma Cobalt-Chrome Total Knee
      Replacement.
AB  - Total knee arthroplasty (TKA) is reliant on safe and effective implants. The
      Press Fit Condylar Sigma Cobalt-Chrome (PFCSCC) was introduced in 2006, but no
      reports have examined long-term failure rates and patient-reported outcome
      measures (PROMs). The primary aim of this study was to assess survival outcomes
      of the PFCSCC at 10 years after implantation. Prospective data collection was
      performed on all patients undergoing primary TKA in one orthopaedic department
      using this prosthesis exclusively from February 1, 2006, to January 31, 2007.
      Follow-up was at 10 years. Survival analysis was performed using two primary
      outcome measures: (1) all-cause joint revision and (2) aseptic revision.
      Secondary outcomes measures included the American Knee Society Score (AKSS) and
      Oxford Knee Score (OKS). In total, 249 knees of 233 patients underwent primary
      TKA. Mean patient age was 66.7 years (range 34-80), and mean body mass index
      (BMI) was 30 kg/m2 (20.7-40.1). Reviewing all causes of revisions, 14 joints
      (5.6%) of 14 patients required reoperation. Of these, nine were for deep
      infection, including six in the first year. Four (1.6%) underwent aseptic
      revision. Mean AKSS changed from 47.6 to 90.4 (n = 140; p < 0.001) at 10 years,
      and mean OKS changed from 38.3 to 23.2 (n = 149; p < 0.001). Prospective analysis
      of consecutive TKA cases using this design of prosthesis demonstrated high
      survival rates of 94.4% (all-cause revision) and 98.4% (aseptic revision) at 10
      years. Postoperative gains in PROMs were sustained at 10 years. These real-world
      data represent a substantial extension to previous reports for the PFCSCC and
      suggest that it is not prone to late mechanical failure.

PMID- 29635649
TI  - Achieving Minimum Clinically Important Difference in Oxford Knee Score and Short
      Form-36 Physical Component Summary Is Less Likely with Single-Radius Compared
      with Multiradius Total Knee Arthroplasty in Asians.
AB  - Single-radius (SR) and multiradius (MR) total knee arthroplasties (TKAs) have
      produced similar outcomes, albeit most studies originate from Western nations.
      There are known knee kinematic differences between Western and Asian patients
      after TKA. The aim of this study is to compare the short-term patient-reported
      outcome measures (PROMs) of SR-TKA versus MR-TKA in Asians. Registry data of 133
      SR-TKA versus 363 MR-TKA by a single surgeon were analyzed. Preoperative and 2
      year postoperative range of motion (ROM) and PROMs were compared with Student's t
      test and Mann-Whitney U-test. Logistic regression model was used to evaluate the
      odds of SR-TKA or MR-TKA achieving the minimum clinically important difference
      (MCID) of studied outcomes. Patients in both groups had similar age (65.7 +/- 7.6
      vs. 65.8 +/- 8.2 years; p = 0.317), gender proportion (71% females vs. 79%
      females; p = 0.119), and ethnic distribution (80% Chinese vs. 84% Chinese; p =
      0.258). Preoperatively, there were no statistically significant differences
      between both groups for ROM, Knee Society Score (KSS), Oxford Knee Score (OKS),
      and Short Form (SF)-36 scores. At 2 years, all outcomes were statistically
      similar or failed to achieve a difference of MCID. Controlling for all
      preoperative variables, SR-TKA has significantly lower odds of achieving MCID for
      OKS (odds ratio [OR]: 0.275, 95% confidence interval [CI]: 0.114-0.663; p =
      0.004) and SF-36 Physical Component Summary (PCS) (OR: 0.547; 95% CI: 0.316
      0.946; p = 0.031) compared with MR-TKA. In conclusion, there are no significant
      differences in the absolute PROMs between SR-TKA and MR-TKA at 2 years following
      TKA in Asians. However, SR-TKA has significantly lower odds of achieving the MCID
      for OKS and SF-36 PCS.

PMID- 29635650
TI  - Expression of LOXs and MMP-1, 2, 3 by ACL Fibroblasts and Synoviocytes Impact of
      Coculture and TNF-alpha.
AB  - This study aims to confirm the effects of synoviocytes (SCs) on regulating lysyl
      oxidases (LOXs) and matrix metalloproteinase (MMP)-1, 2, 3 in the normal and
      injured anterior cruciate ligament (ACL) fibroblasts response to tumor necrosis
      factor-alpha(TNF-alpha). The gene and protein expression levels of LOXs and MMP
      1, 2, 3 in SCs cocultured ACL fibroblasts (ACLfs) induced by TNF-alpha and
      mechanical injury were analyzed by real-time polymerase chain reaction (PCR) and
      western bolting; the MMP-2 activity were analyzed by zymography. The results
      exhibited that TNF-alpha alone slightly downregulated the expressions of LOXs and
      upregulated the expression of MMP-1, 2, 3 in both normal and injured ACL
      fibroblasts. The decrease of LOXs and increase of MMP-1, 2, 3 in ACLfs response
      to TNF-alpha were further promoted by coculture. Taken together, these results
      show for the first time that the crosstalk between ACLfs and SCs could modulate
      the LOXs and MMP-1, 2, 3 synthesis in ACLfs in the presence of TNF-alpha.
      Accumulation of MMPs in the isolated fluid-containing space not only disrupts the
      balance of ACL healing, but also increases cartilage degradation and accelerates
      osteoarthritis (OA) in injured joint. Based on this mechanism, targeting
      inhibition of MMPs could provide a promising therapeutic strategy for acute
      ligament injury.

PMID- 29635651
TI  - Congenital Esophageal Atresia-Surgical Treatment Results in the Context of
      Quality of Life.
AB  - INTRODUCTION:  Esophageal atresia (EA) is one of the most frequent congenital
      malformations of the gastrointestinal tract. The aim of the study was to assess
      surgical treatment results in the context of the quality of life (QoL) of
      children after correction of EA. MATERIALS AND METHODS:  The data were collected
      among 73 patients after surgery of EA. The work diagnostic survey method was
      applied using authors' own questionnaire and standardized questionnaire, the
      PedsQL 4.0 generic core scales. Analysis of children growth was done based on
      World Health Organization percentile charts for body height and weight. Medical
      background for each patient, including demographic data, type of EA, type of
      delivery, the age of gestation, associated anomalies, mode of repair-primary and
      subsequent, if applicable, was collected from clinical records. Additional
      anomalies were divided into cardiac, skeletal, respiratory, renal, central
      nervous system, and other malformations (VACTERL association, CHARGE syndrome,
      trisomy chromosomes 18 and 21, and others). RESULTS:  In this study, 23% of
      children in the study group weighted below third percentile, 36% were born
      between 33rd and 37th week of gestation; 56% had at least one associated
      congenital anomalies. The QoL of children born before 37th week of gestational
      age was lower (p < 0.034) in social functioning than children born in term. The
      presence of concomitant anomalies does affect the overall generic QoL. No
      statistical correlation was found between the type of anomaly (with/without TEF)
      and patients' QoL. CONCLUSION:  It seems to be needed to extend psychological
      care of premature infants with EA.

PMID- 29635652
TI  - Relationship between In Vitro Fertilization and Neonatal Outcomes in Very Low
      Birth Weight Preterm Infants.
AB  - OBJECTIVE:  To assess the association of in vitro fertilization (IVF) with
      neonatal outcomes and duration of stay in neonatal intensive care unit (NICU)
      among very low birth weight (VLBW) preterm infants. METHODS:  This was a cohort
      study of VLBW preterm infants admitted to NICU over 15 years. We assessed
      neonatal outcomes including composite outcome of mortality or severe morbidity,
      risk for major birth defects, survival without severe morbidity, and the duration
      of NICU stay across three birth-year epochs. RESULTS:  A total of 1,533 infants
      were eligible for data analysis. Of these, 236 were born following IVF and 1,297
      were born following spontaneous conception (SC). After adjustment for baseline
      variables, regression analysis revealed no statistically significant differences
      between IVF and SC groups in terms of the composite outcome of mortality or
      severe morbidity, risk for major birth defects, survival without severe
      morbidity, or duration of NICU stay. CONCLUSION:  Among VLBW preterm infants, IVF
      had no detectable relationship with neonatal outcomes and duration of NICU stay.
      These findings can help provide guidance in professional counseling of affected
      families.

PMID- 29635653
TI  - Might Bilirubin Serve as a Natural Antioxidant in Response to Neonatal
      Encephalopathy?
AB  - BACKGROUND:  Neonatal asphyxia is often associated with hepatic injury. We
      hypothesized that this might lead to increased bilirubin concentrations. STUDY
      DESIGN:  Term neonates admitted between January 2015 and April 2017 who remained
      hospitalized for >= 4 days and who had serial serum bilirubin concentrations
      recorded were divided into those with neonatal encephalopathy (NE) and controls.
      Serial serum bilirubin concentrations during the first days of life were compared
      between groups. RESULTS:  Twenty-nine neonates with NE and 84 age-matched
      controls were identified. Mean total serum bilirubin concentrations of NE babies
      were significantly lower than those controls throughout the first days of life.
      At 96 hours of age, NE serum bilirubin concentrations were 4.5 (3.2, 5.8) versus
      controls of 10.5 (9.4, 11.5) mg/dL (p < 0.0001). The mean area under the curve
      (AUC) for the NE group was 268 (215, 321) versus 663 (608, 718), p < 0.0001, for
      the control group. All of the NE babies remained below the 40th percentile of the
      Bhutani curve and none required phototherapy. CONCLUSION:  Contrary to our
      hypothesis, bilirubin concentrations in NE infants are significantly lower than
      expected during the first 4 days postnatally. We speculate that, under conditions
      of severe oxidative stress, bilirubin is consumed as an antioxidant.

PMID- 29635654
TI  - Acute Hypoxia Induces Enkephalin Production and Release in an Adrenergic Cell
      Line Model of Neonatal Chromaffin Cell Responses to Hypoxic Stress.
AB  - OBJECTIVE:  Prior to maturation of the human sympathetic nervous system, the
      neonatal adrenal medulla senses and responds to hypoxia. In addition to
      catecholamine release, the adrenal medulla synthesizes and stores opioid
      peptides, notably enkephalin (ENK). However, it is not known whether acute
      hypoxia evokes adrenal ENK production and release, as seen in the central nervous
      system (CNS). We hypothesize that acute hypoxia stimulates synthesis and release
      of ENK in chromaffin cells. STUDY DESIGN:  Cultures of adrenergic mouse
      pheochromocytoma cells (MPC) 10/9/96CR were incubated in 10% oxygen (O2) at
      intervals of up to 60 minutes. ENK content and release were measured by Met-ENK
      enzyme-linked immunosorbent assay (ELISA). ENK messenger ribonucleic acid (mRNA)
      was analyzed by quantitative reverse-transcriptase polymerase chain reaction
      (PCR). RESULTS:  Incubation of MPC 10/9 cells in 10% O2 evoked rapid release of
      epinephrine and of Met-ENK which increased approximately twofold in 15 minutes.
      Reduced [O2] also induced an overall increase (14%) in cellular ENK peptide
      content within 60 minutes. Acute hypoxia-stimulated release of Met-ENK was
      accompanied by increased mRNAENK expression in MPC 10/9s, a cell culture model of
      adrenergic chromaffin cells. CONCLUSION:  We speculate that the ability of
      reduced [O2] to evoke ENK release from chromaffin cells may influence blood
      pressure regulation and heart contractility, thereby providing an adaptive
      survival advantage during neonatal asphyxia.

PMID- 29635655
TI  - Are Anti-beta2 Glycoprotein 1 Antibodies Associated with Placenta-Mediated
      Pregnancy Complications? A Nested Case-Control Study.
AB  - BACKGROUND:  While anti-beta2 glycoprotein 1 (anti-beta2GP1) antibody positivity
      is included in the diagnostic criteria for antiphospholipid syndrome (APS), the
      association between anti-beta2GP1 and the obstetrical complications of APS has
      been inconsistently reported and remains unclear. OBJECTIVE:  We completed a case
      control study nested within the Canadian Ottawa and Kingston (OaK) Birth Cohort
      to evaluate the association between anti-beta2GP1 antibody positivity and
      placenta-mediated pregnancy complications. STUDY DESIGN:  Five hundred cases were
      randomly selected among pregnant women who experienced any of the following
      independently adjudicated placenta-mediated pregnancy complications:
      preeclampsia, placental abruption, late pregnancy loss (>= 12 weeks' gestation),
      and birth of a small-for-gestational age (SGA) infant < 10th percentile. Five
      hundred pregnant women without any placenta-mediated pregnancy complications were
      selected as controls. Stored blood samples were analyzed for the presence of anti
      beta2GP1 antibodies by enzyme-linked immunosorbent assay. RESULTS:  Anti-beta2GP1
      immunoglobulin G (IgG) and/or immunoglobulin M (IgM) antibodies in titers >= 20
      G/M units (> 99th percentile) were present in 24 of 497 (4.8%) of controls and 33
      of 503 (6.6%) of cases. There was no significant difference between cases and
      controls for the composite outcome of any placenta-mediated pregnancy
      complications (odds ratio, 1.38, 95% confidence interval [CI], 0.8-2.37, p =
      0.25). CONCLUSION:  Our results call into question the association between anti
      beta2GP1 antibodies and placenta-mediated pregnancy complications, with further
      research needed.

PMID- 29635656
TI  - Preterm Pulmonary Hemorrhage Is Associated with Multiple Births but Not with
      Intracytoplasmic Sperm Injection: A Cohort Study on Medical Records.
AB  - OBJECTIVE:  Pulmonary hemorrhage (PH) is a severe complication in preterm
      neonates. This study aims to identify risk factors and comorbidities of PH. STUDY
      DESIGN:  A single-center cohort study on medical records including all preterm
      neonates of <30 weeks' gestational age was conducted in the neonatal intensive
      care unit of Universitatsklinikum Aachen, Germany. The occurrence of PH served as
      a primary end point. Gestational age, birthweight, sex, multiple births,
      intracytoplasmic sperm injection (ICSI), intubation, surfactant, antenatal
      steroids, intraventricular hemorrhage (IVH), amniotic infection syndrome, and
      persistent ductus arteriosus were studied as risk factors. RESULTS:  In this
      study, 344 preterm neonates were included, of whom 36 suffered from PH (10.5%).
      The mean time of the first occurrence was the third day of life (standard
      deviation [SD]: 1.2). On average, the patients suffered from 1.5 incidents (SD:
      0.8) of PH, of whom 50% were severe. Preterm neonates born as multiples (95%
      confidence interval [CI]: 3.1, 26.9) and those who suffered from IVH (95% CI:
      2.7, 18.9) had a significantly increased risk of PH. ICSI was not an independent
      risk factor. CONCLUSION:  PH is significantly associated with IVH and multiple
      births but not with ICSI. The identification of patients at risk allows to apply
      prophylactic strategies of ventilation and pharmacological treatment.

PMID- 29635657
TI  - ?

PMID- 29635658
TI  - [Rare Differential Diagnosis of a Neonatal Bacterial Sepsis: The Neonatal Viral
      Myocarditis].
AB  - The neonatal bacterial infection is a potentially life-threatening condition that
      justifies intravenous antibiotic therapy. However, clinical symptoms are often
      unspecific. Particularly in the absence of a response to antibiotic therapy,
      various differential diagnoses can be considered. We report the clinical
      presentation, the diagnostic steps, the therapy as well as the long-term
      progression of a preterm infant who acquired a perinatal enterovirus infection
      including viral myocarditis. The case underlines the clinical relevance of
      enterovirus infections in newborns. The current literature, however, describes
      only single aspects and lacks, in particular, accurate data on both epidemiology
      and morbidity.

PMID- 29635659
TI  - ?

PMID- 29635660
TI  - ?

PMID- 29635661
TI  - [Editor's Comment].

PMID- 29635662
TI  - ?

PMID- 29635663
TI  - ?

PMID- 29635664
TI  - ?

PMID- 29635667
TI  - [Techniques of stapedotomy].

PMID- 29635668
TI  - [Laryngopharyngeal Reflux].
AB  - The prevalence of laryngopharyngeal reflux (LPR) is around 31 % in the general
      population. Patients with a dysphonia or other laryngeal diseases are accompanied
      up to 50 % by an LPR. Typical reflux associated diseases of the larynx are a
      chronical laryngitis and a contact granuloma. The role of LPR is still not
      clarified in the development of a glottic carcinoma. There still doesn't exist
      evidence based data for the diagnosis of a LPR. Therefore LPR is usually
      clinically diagnosed by a combination of typical symptoms like hoarseness,
      chronic coughing, relapsing throat clearing, globus pharyngis and dysphagia as
      well as through the laryngoscopic characteristics like mucosal erythema, mucosal
      hyperplasia with plication of the interarytenoid region and an edema of the vocal
      cords. Occasionally the LPR can be ensured with the additional method of the
      pharyngeal 24-hour pH-monitoring. The therapy of the LPR is a multimodal for
      example dietary arrangements, medication with proton pump inhibitors and where
      indicated a surgical intervention. The treatment of a symptomatic patient is
      administered by proton pump inhibitors in a close dialog with the ENT
      practitioner and the gastroenterologist.

PMID- 29635669
TI  - [The correct handling of bonus miles].

PMID- 29635670
TI  - [Endoscopic early diagnosis of carcinomas in upper respiratory and digestive
      tract].
AB  - Modern endoscopic imaging techniques make it possible to detect tumor diseases of
      the upper respiratory and digestive tract and treat them minimally invasive -
      with a good oncologic outcome and maintaining the functionality of the
      tissue.Horizontal techniques permit the inspection of big mucous membrane
      surfaces, searching vor areas suspicious of dysplasia or tumor. They can be used
      as screening techniques. Vertical techniques serve for precise examination of in
      depth expansion, infiltration chraracteristics and dignity of known lesions.
      Cellular techniques deal with the detection of cellular changes in vivo. As the
      techniques have different advantages and disandvantages, it is recommended to
      combine several techniques for best diagnostic gains.

PMID- 29635671
TI  - ?

PMID- 29635672
TI  - ?

PMID- 29635673
TI  - HPLC-ESI-MS Characterization of Certain Polyphenolic Compounds of Carica papaya
      L. Fruit Extracts and Evaluation of Their Potential Against Murine
      Schistosomiasis mansoni.
AB  - The in vivo antischistosomal activities of Carica papaya L. extracts were
      evaluated and the characterization of the active secondary metabolites of the
      defatted methanolic extract was performed using HPLC-ESI-MS. The plant fruit
      powders were extracted with 85% methanol and fractionated using organic solvents.
      The in vivo antischistosomal effects of the methanolic extracts and its
      fractions, as well as the assessment of the relationship between the
      antischistosomal activity of these plant extracts and oxidative stress, was
      determined. In addition, the defatted methanolic extract was characterized by
      HPLC-ESI-MS analysis. The number of worms, ova, and the Oogram pattern displayed
      typical Schistosoma mansoni pathology 8 weeks after infection in mice. Treatment
      of the infected group with the defatted methanolic extracts significantly
      decreased worm burden, immature ova and mature ova, while increasing the
      percentage of dead ova in vivo. The butanol fraction was the most effective
      fraction reducing worm burden by 77%, ova count in the intestine by 76% and in
      the liver by 80%, and significantly decreased immature and mature ova (P<0.001)
      compared to the infected group. Additionally, the defatted methanolic extracts
      improved the reduced glutathione and malondialdehyde levels in hepatic tissues in
      the treated groups compared to the infected group. The HPLC-ESI-MS analysis of
      the Carica papaya defatted methanolic extract revealed the presence of several
      polyphenolic compounds. Carica papaya fruit extracts are rich with phenolic acids
      and flavonoids and show a significant effect against S. mansoni infections which
      may be used alternative to PZQ as anti-schistosomal drug against schistosomiasis.

PMID- 29635674
TI  - Anti-Obesity Effect of Arq Zeera and Its Main Components Thymol and Cuminaldehyde
      in High Fat Diet Induced Obese Rats.
AB  - Arq zeera is a distillate product that prepared from four different herbs namely
      Trachyspermum ammi L., apiaceae, Zingiber officinale Roxb., zingiberaceae, Carum
      carvi L.,apiaceae and Cuminum cyminum L., apiaceae. The present study aims to
      determine the antiobesity effect of arq zeera and its main components thymol and
      cuminaldehyde in high fat diet induced obese rats and to explore its mechanism of
      action. In current study, orlistat was used as positive controls. Male Wistar
      rats were fed with HFD for 42 days to induce obesity. HFD-fed rats were
      administered with arq zeera, thymol, cumic aldehyde, thymol + cuminaldehyde and
      orlistat for 28 days. During the course of treatment, body weight and food intake
      frequently observed and after end of treatments, liver weight, visceral fat pad
      weight, plasma lipid proflie, alanine aminotransferase, aspartate
      aminotransferase, glucose, insulin, leptin levels and pancreatic lipase activity
      were studied on all treated obese rats. The histopathology of liver was also
      studied. After the treatments of arq zeera and its main components, body weight,
      food intake, liver weight, visceral fat pad weight and the level of lipid
      profile, alanine aminotransferase, aspartate aminotranferase, glucose, insulin,
      and leptin were found to be decreased and pancreatic lipase inhibition were
      increased. Arq zeera showed more potential antiobesity effect than orlistat.
      According to our present findings, arq zeera and its main components possessed
      potent antiobesity effect on high fat diet -induced obese rats and excreted anti
      obesity effect partly via hypolipidemic, hypoglycemic, hypoinsulinemic,
      hypoleptinemic and pancreatic lipase inhibition action.

PMID- 29635675
TI  - [Submucosal supraglottic mass: A first case report].

PMID- 29635676
TI  - [Painless tumor of the facial bone with osseous arrosion and secondary mucocele
      of the frontal sinus].

PMID- 29635677
TI  - [Altered indication for parotidectomy in north-western Brandenburg: A
      longitudinal study].
AB  - OBJECTIVE: Knowledge about parotoidectomy indications is based on notifications
      to ENT departments and tumor databases. The study investigates the hypothesis
      that the surgical indication for parotoidectomy has changed over recent years.
      MATERIAL AND METHODS: We performed a retrospective observation study of patients
      who underwent parotidectomy between 1975 and 2016 (subdivided into 4 quartiles)
      in a teaching hospital of a medical university. RESULTS: 405 men and 366 women
      underwent operation for benign tumors (600/78 %), malignant tumors (116/15 %) or
      parotitis (55/7 %). The proportion of benign tumors remained unchanged (78 %),
      whereas malignant tumors increased (7 % - 23 %) and parotitides decreased (17 % -
      < 1 %). In benign tumors, the proportion of pleomorphic adenomas decreased (60 % 
      24 %), whereas Warthin tumors increased (23 % - 58 %). Among malignant tumors,
      the proportion of metastases increased from 2/13 to 31/49 (in particular squamous
      cell carcinomas of the skin). CONCLUSIONS: The present the study shows the
      decreasing importance of parotitis as an indication for parotidectomy due to
      improved non-surgical procedures. The increasing prevalence of Warthin tumors was
      associated with an increasing proportion of smokers. Increased number of
      malignant tumors was caused by an increased prevalence of intraparotidial
      matastases of cutaneous squamous cell carcinoma. The presented results are based
      on the evaluation of patient charts. Due to their ICD or DRG reference,
      histological findings cannot be generated by evaluating databases. For this
      purpose, a special salivary gland tumor database should be established.

PMID- 29635678
TI  - [Prediction of modality-specific working memory performance in kindergarten age].
AB  - OBJECTIVE: Working memory (WM) as a central cognitive construct is a fundamental
      prerequisite for learning and provides a marker of developmental disorders. It
      has received considerable attention in recent years. Here, multivariate
      regression analyses using generalized linear models were conducted to determine
      predictor variables for phonological and visuospatial WM. MATERIAL AND METHODS:
      The phonological WM was investigated by repetition of non-words (subtest PGN of
      the German SETK 3-5) and number recall (K-ABC-subtest), the visuospatial WM by
      the imitation of a sequence hand movements (K-ABC-subtest hand movements). The
      estimation of intelligence was operationalized by the performance in the K-ABC
      scale "Simultaneous Processing". SAMPLE: Kindergarten kids (N = 169; 49 % boys;
      51 % girls), mostly with migration background and German as second language (mean
      age: 45.9; SD 6.2; min 36, max 61 months). They visited the kindergarten at the
      time of testing for 9.9 (SD 6.9) months, on average and had an average
      intelligence. Independent variables were chronological age, gender, kindergarten
      attendance until the test examination, intelligence, migration background.
      RESULTS: Both phonological and visuospatial working WM performance were on
      average not reduced. Chronological age and simultaneous processing were found to
      be significant predictors for the performance in all WM tests. CONCLUSION: In the
      age from 36 to 61 months both working memory systems can be described as a
      congenital, maturity-dependent and rather gender non-specific mechanism.

PMID- 29635679
TI  - [Internal Validation of the Acoustic Voice Quality Index version 03.01 und
      Acoustic Breathiness Index].
AB  - OBJECTIVE: Acoustics might have the potential to objectify voice quality (eg,
      hoarseness and breathiness). The Acoustic Voice Quality Index (AVQI) and the
      Acoustic Breathiness Index (ABI) revealed sufficient valid and reliable results
      in the evaluation of voice quality. The aim of the present study is to validate
      the recent version of AVQI 03.01 and ABI in their internal validation. The
      responsiveness of change is evaluated on the hoarseness and breathiness severity
      after voice therapy. MATERIALS AND METHODS: In total, 84 voice samples of
      continuous speech and sustained vowel [a:] before and after a voice therapy were
      used. All 42 subjects presented organic and nonorganic voice disorders and
      various degrees of dysphonia severity before and after behavioral voice therapy.
      The voice samples were judged by three voice experts using the RBH-scale, which
      is based on the GRBAS-scale. RESULTS: The intra-rater reliability was high for
      hoarseness (mean kappa = 0.76) and breathiness (mean kappa = 0.69).The inter
      rater reliability was lower for both voice quality characteristics and ranged
      between kappa = 0.27 to 0.29. A strong correlation was identified between the
      perceived rating of hoarseness and breathiness and AVQI and ABI before and after
      voice therapy (r = 0.715, p < 0.01, and r = 0.712, p < 0.01, respectively).
      Additionally, no significant differences were revealed. CONCLUSION: The present
      results showed that AVQI version 03.01 und ABI had a high internal validity to
      assess voice changes after voice therapy. AVQI and ABI are two valid and robust
      voice measures to objectify hoarseness and breathiness.

PMID- 29635680
TI  - [Aerobic exercises worsen the detection threshold of short H2S pulses].
AB  - BACKGROUND: Whether smelling is reduced during aerobic exercise is described
      contradictorily in the sparse literature. MATERIAL AND METHODS: To clarify this
      question, in healthy subjects the passive detection thresholds for short H2S
      stimuli were determined by means of a flow olfactometer in an inspiration
      synchronous manner during nasal breathing in a staircase procedure during a
      resting phase, a subsequent submaximal load on a bicycle ergometer and a
      subsequent recovery phase. In parallel, the measurements of heart rate, blood
      pressure, blood lactate and body temperature were monitored to confirm an aerobic
      exercise. RESULTS: The participants achieved the highest values for the detection
      threshold in the load phase. By means of rm-ANOVA and post-hoc tests, a
      significant difference in the mean values of detection thresholds between the
      measurements at rest and during cycling as well as between the recovery and load
      phases was observed. However, the mean values of the detection thresholds between
      the resting and recovery phases did not differ. CONCLUSION: The worsening of
      olfactory detection thresholds during acute aerobic physical exercise and their
      immediate improvement during recovery phase to rest values suggests that the
      detection threshold is influenced by exercise. The most probable cause for this
      is a dilution effect caused by additional inflowing neutral ambient air in the
      case of forced nasal breathing.

PMID- 29635681
TI  - [Validation of the German version of Eating Assessment Tool for head and neck
      cancer patients].
AB  - OBJECTIVE: The assessment of subjective swallowing complaints constitutes an
      important element in a multidimensional, modern management of head and neck
      cancer patients suffering from dysphagia. For this purpose, an internationally
      recognized and validated 10-item questionnaire EAT-10 is used that was developed
      and validated by Belafski et al. in 2008. The purpose of the present study is the
      translation of EAT-10 into the German language and its validation for head and
      neck cancer patients. MATERIAL AND METHODS: After the translation of EAT-10 into
      German according to the guidelines for the translation of foreign measuring
      instruments, a validation of gEAT-10 was carried out on the basis of the sample
      of 210 head and neck cancer patients. The reliability was determined by means of
      the internal consistency (Cronbach's Alpha) and item-total correlations
      (Spearman). The construct validity was verified by the uni- and multivariate
      analyses of the distribution of gEAT-10 total scores depending on gender, age,
      BMI, tumor stage and localization as well as type of the oncological therapy.
      RESULTS: The internal consistency amounted to alpha = .94, the item-total
      correlations varied between rho = .59 and rho = .85. No significant associations
      between gEAT-10 total scores and gender as well as age were identified in
      univariate calculations. Such associations were found for BMI, tumor stage and
      localization as well as type of the oncological therapy. However, only the tumor
      stage yielded a significant result in a regression. CONCLUSIONS: The gEAT-10 was
      shown to be a reliable and construct valid questionnaire for the assessment of
      subjective swallowing complaints in patients with head and neck cancer.

PMID- 29635682
TI  - Hydroxypropyl-beta-cyclodextrin-containing hydrogel enhances skin formononetin
      permeation/retention.
AB  - OBJECTIVES: This study was aimed to investigate the in vitro permeation potential
      of hydrogel formulations containing the isoflavones formononetin and biochanin A
      and cyclodextrins in different combinations. METHODS: The permeation assay was
      performed using porcine skin discs on Franz diffusion cells model. The isoflavone
      contents of the formulations were quantified in the different layers of the skin
      using a validated HPLC-PDA method. KEY FINDINGS: The isoflavones individually
      incorporated into the formulations showed high permeation potential, especially
      formononetin, after the incorporation of hydroxypropyl-beta-cyclodextrin that
      enhanced its permeation in the epidermis and dermis. Biochanin A showed 2.7 times
      of permeation capacity in the epidermis and dermis mainly after incorporation of
      cyclodextrins in the formulations. Formononetin showed reduction in its
      permeation when incorporated in the formulations together to biochanin A, showing
      the absence of synergism. CONCLUSIONS: Our results indicated a noticeable skin
      permeation promoting effect of HPbetaCD in formononetin formulation. Furthermore,
      formononetin and biochanin A can permeate the skin being mostly retained in the
      epidermis and dermis, revealing its potential use in cosmetic preparations
      intended to prevent skin aging.

PMID- 29635683
TI  - Assessment of burbot Lota lota (L. 1758) population sustainability in central
      European reservoirs.
AB  - A novel sampling scheme, using a combination of electrofishing, visual
      exploration by scuba divers, two types of fyke nets and longlines, was tested in
      four reservoirs (including their inlets and outlets) to monitor a population of
      burbot Lota lota. This was supplemented by fry trawling and vertical hydro
      acoustics, to detect L. lota larvae in two deep reservoirs that have had a long
      term stocking programme. The majority of the L. lota detected were juveniles,
      captured by electrofishing in the littoral zones of the reservoirs and in running
      waters. Older individuals were rarely captured with longlines or fyke nets in
      deeper zones or structured habitats within the reservoirs. A combination of
      multiple sampling methods provided an assessment of the whole population.
      Population establishment could not be demonstrated as the age structure of the
      sampled fish corresponded with that of the stocked fish. Low post-stocking
      survival, migratory behaviour, interactions with other species and warmer water
      temperatures are considered the potential drivers for unsuccessful establishment
      of L. lota populations in these reservoirs.

PMID- 29635684
TI  - Catch composition and aspects of the biology of sharks caught by Thai commercial
      fisheries in the Andaman Sea.
AB  - Catch composition, landing patterns and biological aspects of sharks caught by
      commercial fishing fleet operating in the Andaman Sea were recorded from landing
      sites in Ranong province of Thailand over a period of 1 year. Of the 64 species
      previously reported in the existing Thailand checklist, only 17 species were
      recorded in this study. Shark landings from the Andaman Sea appear now to be
      dominated largely by bamboo sharks Chiloscyllium spp. (Hemiscylliidae), which
      contribute c. 65% of the total number of sharks recorded. The carcharhinid sharks
      comprised c. 30.5% to the total catch, while the remaining c. 4.5% of landings
      comprised sharks from the families Squalidae, Stegostomatidae, Sphyrnidae and
      Triakidae. The catch composition is remarkably different from the previous
      landing survey in 2004, in that the current study found noticeable declines in
      landings of slow-growing, late- maturing and low-fecundity species (especially
      sphyrnid and carcharhinid species). The absences of many species and changes in
      life-stage composition suggest that the populations of these groups may be close
      to collapse. The results from this study emphasize the urgency for additional
      research and monitoring efforts and also the need for management incentives in
      order to manage shark fisheries effectively in the Andaman Sea.

PMID- 29635686
TI  - The anatomy and physiology of the terminal thoracic duct and ostial valve in
      health and disease: potential implications for intervention.
AB  - The thoracic duct (TD) transports lymph drained from the body to the venous
      system in the neck via the lymphovenous junction. There has been increased
      interest in the TD lymph (including gut lymph) because of its putative role in
      the promotion of systemic inflammation and organ dysfunction during acute and
      critical illness. Minimally invasive TD cannulation has recently been described
      as a potential method to access TD lymph for investigation. However, marked
      anatomical variability exists in the terminal segment and the physiology
      regarding the ostial valve and terminal TD is poorly understood. A systematic
      review was conducted using three databases from 1909 until May 2017. Human and
      animal studies were included and data from surgical, radiological and cadaveric
      studies were retrieved. Sixty-three articles from the last 108 years were
      included in the analysis. The terminal TD exists as a single duct in its terminal
      course in 72% of cases and 13% have multiple terminations: double (8.5%), triple
      (1.8%) and quadruple (2.2%). The ostial valve functions to regulate flow in
      relation to the respiratory cycle. The patency of this valve found at the
      lymphovenous junction opening, is determined by venous wall tension. During
      inspiration, central venous pressure (CVP) falls and the valve cusps collapse to
      allow antegrade flow of lymph into the vein. During early expiration when CVP and
      venous wall tension rises, the ostial valve leaflets cover the opening of the
      lymphovenous junction preventing antegrade lymph flow. During chronic disease
      states associated with an elevated mean CVP (e.g. in heart failure or cirrhosis),
      there is a limitation of flow across the lymphovenous junction. Although lymph
      production is increased in both heart failure and cirrhosis, TD lymph outflow
      across the lymphovenous junction is unable to compensate for this increase. In
      conclusion the terminal TD shows marked anatomical variability and TD lymph flow
      is controlled at the ostial valve, which responds to changes in CVP. This
      information is relevant to techniques for cannulating the TD, with the aid of
      minimally invasive methods and high resolution ultrasonography, to enable
      longitudinal physiology and lymph composition studies in awake patients with both
      acute and chronic disease.

PMID- 29635685
TI  - The pig as a preclinical model for predicting oral bioavailability and in vivo
      performance of pharmaceutical oral dosage forms: a PEARRL review.
AB  - OBJECTIVES: In pharmaceutical drug development, preclinical tests in animal
      models are essential to demonstrate whether the new drug is orally bioavailable
      and to gain a first insight into in vivo pharmacokinetic parameters that can
      subsequently be used to predict human values. Despite significant advances in the
      development of bio-predictive in vitro models and increasing ethical expectations
      for reducing the number of animals used for research purposes, there is still a
      need for appropriately selected pre-clinical in vivo testing to provide guidance
      on the decision to progress to testing in humans. The selection of the
      appropriate animal models is essential both to maximise the learning that can be
      obtained from such experiments and to avoid unnecessary testing in a range of
      species. KEY FINDINGS: The present review, provides an insight into the
      suitability of the pig model for predicting oral bioavailability in humans, by
      comparing the conditions in the GIT. It also contains a comparison between the
      bioavailability of compounds dosed to both humans and pigs, to provide an insight
      into the relative correlation and examples on why a lack of correlation may be
      observed. SUMMARY: While there is a general trend towards predicting human
      bioavailability from pig data, there is considerable variability in the data set,
      most likely reflecting species specific differences in individual drug
      metabolism. Nonetheless, the correlation between pigs vs. humans was comparable
      to that reported for dogs vs. humans. The presented data demonstrate the
      suitability of the pig as a preclinical model to predict bioavailability in
      human.

PMID- 29635687
TI  - The inter-observer agreement in the assessment of carotid plaque
      neovascularization by contrast-enhanced ultrasonography: The impact of plaque
      thickness.
AB  - BACKGROUND: The interobserver agreement in the assessment of the grade of carotid
      plaque neovascularization by contrast-enhanced ultrasonography is poorly
      established. METHOD: We examined 140 carotid plaques in 66 patients (all patients
      had bilateral plaques, and 8 patients had 2 plaques on one side). We performed
      conventional and contrast-enhanced ultrasonography to analyze the presence of
      carotid plaque neovascularization, which was graded by two independent observers
      whose interobserver agreement (kappa) was evaluated according to the thickness of
      carotid plaque. RESULTS: For all carotid plaques, the mean kappa was 0.689 (95%
      confidence interval 0.604-0.774). It was 0.689 (0.569-0.808), 0.637 (0.487
      0.787), and 0.740 (0.585-0.896), respectively for carotid plaques with maximal
      thickness <2 mm, from 2 mm to 3 mm, and >3 mm. CONCLUSION: The interobserver
      agreement for assessing carotid plaque neovascularization by using contrast
      enhanced ultrasonography is substantial and acceptable for research purposes,
      regardless of the maximal thickness of the plaque.

PMID- 29635688
TI  - Umbilical cord arterial base deficit and arterial pH as predictors of adverse
      outcomes among term neonates.
AB  - OBJECTIVE: To determine the importance of arterial pH and arterial base deficit
      (ABD) for predicting adverse outcomes among all term neonates, regardless of
      acidemic status. METHODS: The present observational cohort study included
      consecutive term, non-anomalous singleton neonates with validated paired cord gas
      data at a single UK teaching hospital between June 23, 2005, and December 31,
      2009. Outcomes included encephalopathy (Sarnat grade 2-3) and/or death; 5-minute
      Apgar score below 7; a composite neurologic adverse outcome; and systemic
      involvement. Comparison of areas under the curve and hierarchical logistical
      regressions were used to examine the importance of arterial pH and arterial base
      deficit (ABD) in predicting adverse outcomes. RESULTS: There were 8759 neonates
      included. In all, 111 (1.3%) neonates had high ABD (>=12 mmol/L). Encephalopathy
      and/or death was recorded in 17 (0.2%) neonates in the whole cohort and 6 (5.4%)
      from the high ABD group. The mean arterial pH values for these two groups were
      7.23 and 7.03, respectively. Comparison of the area under the receiver operating
      characteristic curves showed that adding ABD to arterial pH did not improve the
      prediction. Further, hierarchical logistic regression analysis demonstrated that
      ABD was not an independent predictor of adverse outcomes when adjusted for
      arterial pH. CONCLUSIONS: ABD demonstrated no predictive value for adverse
      neonatal outcomes beyond using arterial pH alone.

PMID- 29635689
TI  - Large sensitivity in land carbon storage due to geographical and temporal
      variation in the thermal response of photosynthetic capacity.
AB  - Plant temperature responses vary geographically, reflecting thermally contrasting
      habitats and long-term species adaptations to their climate of origin. Plants
      also can acclimate to fast temporal changes in temperature regime to mitigate
      stress. Although plant photosynthetic responses are known to acclimate to
      temperature, many global models used to predict future vegetation and climate
      carbon interactions do not include this process. We quantify the global and
      regional impacts of biogeographical variability and thermal acclimation of
      temperature response of photosynthetic capacity on the terrestrial carbon (C)
      cycle between 1860 and 2100 within a coupled climate-carbon cycle model, that
      emulates 22 global climate models. Results indicate that inclusion of
      biogeographical variation in photosynthetic temperature response is most
      important for present-day and future C uptake, with increasing importance of
      thermal acclimation under future warming. Accounting for both effects narrows the
      range of predictions of the simulated global land C storage in 2100 across
      climate projections (29% and 43% globally and in the tropics, respectively).
      Contrary to earlier studies, our results suggest that thermal acclimation of
      photosynthetic capacity makes tropical and temperate C less vulnerable to
      warming, but reduces the warming-induced C uptake in the boreal region under
      elevated CO2 .

PMID- 29635690
TI  - Are there multiple ways to direct attention in working memory?
AB  - In visual working memory tasks, memory for an item is enhanced if participants
      are told that the item is relatively more valuable than others presented within
      the same trial. Experiment 1 explored whether these probe value boosts (termed
      prioritization effects in previous literature) are affected by probe frequency
      (i.e., how often the more valuable item is tested). Participants were presented
      with four colored shapes sequentially and asked to recall the color of one probed
      item following a delay. They were informed that the first item was more valuable
      (differential probe value) or as valuable as the other items (equal probe value),
      and that this item would be tested more frequently (differential probe frequency)
      or as frequently (equal probe frequency) as the other items. Probe value and
      probe frequency boosts were observed at the first position, though both were
      accompanied by costs to other items. Probe value and probe frequency boosts were
      additive, suggesting the manipulations yield independent effects. Further
      supporting this, experiment 2 revealed that probe frequency boosts are not
      reliant on executive resources, directly contrasting with previous findings
      regarding probe value. Taken together, these outcomes suggest there may be
      several ways in which attention can be directed in working memory.

PMID- 29635691
TI  - Peptides derived from lupin proteins confer potent protection against oxidative
      stress.
AB  - BACKGROUND: Lupin seeds are rich in proteins, which are utilized in the food
      industry. There is an increased interest in lupin research due to its association
      with health-related benefits, such as reduction of hypertension and
      hyperglycemia. However, studies on the peptides derived from lupin proteins are
      rare. RESULTS: Lupin protein hydrolysates (LPHs) were prepared by proteolysis
      using alcalase, trypsin and pepsin, respectively. All the hydrolysates
      demonstrated higher antioxidant and angiotensin I-converting enzyme (ACE)
      inhibitory activities compared to lupin proteins. The hydrolysates were
      fractionated into three fractions based on molecular weight (MW), and the
      peptides with MW < 3 kDa (LPH3) had the highest antioxidant and ACE inhibitory
      activities compared to other fractions. Cell model study revealed that LPH3
      fraction had the highest protection against the generation of reactive oxygen
      species in HepG2 cells, which was associated with increased activities of
      superoxide dismutase and glutathione peroxidase through upregulation of SOD1,
      GPX1, GCLM, SLC7A11 and SRXN1 expression. CONCLUSIONS: The analysis of amino acid
      composition indicated that the peptides were characterized with high content of
      hydrophobic amino acids, which may be responsible for the greatest antioxidant
      activity. This study highlights the promising potential of lupin peptides as a
      functional ingredient in healthy foods. (c) 2018 Society of Chemical Industry.

PMID- 29635692
TI  - Novel insights into Sabino1 and splashed white coat color patterns in horses.
AB  - Within the framework of genome-wide analyses using the novel Axiom(r) genotyping
      array, we investigated the distribution of two previously described coat color
      patterns, namely sabino1 (SBI), associated with the KIT gene (KI16+1037A), and
      splashed white, associated with the PAX3 gene (ECA6:g.11429753C>T; PAX3C70Y ),
      including a total of 899 horses originating from eight different breeds (Achal
      Theke, Purebred Arabian, Partbred Arabian, Anglo-Arabian, Shagya Arabian,
      Haflinger, Lipizzan and Noriker). Based on the data we collected we were able to
      demonstrate that, besides Quarter horses, the PAX3C70Y allele is also present in
      Noriker (seven out of 189) and Lipizzan (three out of 329) horses. The SB1 allele
      was present in three breeds (Haflinger, 14 out of 98; Noriker, four out of 189;
      Lipizzan one out of 329). Furthermore, we examined the phenotypes of SB1- and
      PAX3C70Y -carrier horses for their characteristic white spotting patterns. None
      of the SB1/sb1-carrier horses met the criteria defining the Sabino1 pattern
      according to current applied protocols. From 10 heterozygous PAX3C70Y -carrier
      horses, two had nearly a splashed white phenotype. The results of this large
      scale experiment on the genetic association of white spotting patterns in horses
      underline the influence of gene interactions and population differences on
      complex traits such as Sabino1 and splashed white.

PMID- 29635693
TI  - Preliminary study on the treatment of vitiligo with carbon dioxide fractional
      laser together with tacrolimus.
AB  - BACKGROUND: Tacrolimus is a conventional medication for the treatment of
      vitiligo, but the effect of a single medication is limited. OBJECTIVE: This paper
      aims at observing the effects, adverse responses, and repigmentation results of
      the joint treatment of vitiligo by Carbon dioxide (CO2 ) fractional laser
      together with tacrolimus. METHODS: Forty-five patients with vitiligo were
      randomly divided into two groups: treatment (T) group and control (C) group, and
      each group was further divided into three subgroups (face, torso and limbs, and
      hand and foot) according to the location of the skin defect. Both groups used
      topical 0.1% tacrolimus cream, but the T group was given one CO2 fractional laser
      treatment each month. We observed the clinical efficacy, adverse responses, and
      repigmentation results after 6 months. RESULTS: Compared to the C group, the T
      group showed better improvement in both objective and subjective assessments.
      When the treatment time was increased, the efficacy was also improved, and the
      repigmentation in the T group occured in three ways: perifollicular
      repigmentation, marginal repigmentation and diffuse repigmentation. There were
      three cases of isomorphic responses (2 cases in the rapid progression stage, one
      case in the progression stage), and 1 case formed scarring on the neck in the T
      group. CONCLUSIONS: The treatment of vitiligo by CO2 fractional laser together
      with tacrolimus is significantly effective and is most suitable for patients in
      the progression stage. Patients in the rapid progression stage should use this
      approach with caution, and its efficacy was limited for patients in the stable
      stage. An extended course of treatment is helpful for the repigmentation of white
      patches. All three forms of repigmentation can occur in the joint treatment of
      vitiligo by CO2 fractional laser together with tacrolimus. Lasers Surg. Med.
      50:829-836, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29635694
TI  - Working memory consolidation: insights from studies on attention and working
      memory.
AB  - Working memory, the system that maintains a limited set of representations for
      immediate use in cognition, is a central part of human cognition. Three processes
      have recently been proposed to govern information storage in working memory:
      consolidation, refreshing, and removal. Here, we discuss in detail the
      theoretical construct of working memory consolidation, a process critical to the
      creation of a stable working memory representation. We present a brief overview
      of the research that indicated the need for a construct such as working memory
      consolidation and the subsequent research that has helped to define the
      parameters of the construct. We then move on to explicitly state the points of
      agreement as to what processes are involved in working memory consolidation.

PMID- 29635695
TI  - Is the choice of a standard zeroth-order hamiltonian in CASPT2 ansatz optimal in
      calculations of excitation energies in protonated and unprotonated schiff bases
      of retinal?
AB  - To account for systematic error of CASPT2 method empirical modification of the
      zeroth-order Hamiltonian with Ionization Potential-Electron Affinity (IPEA) shift
      was introduced. The optimized IPEA value (0.25 a.u.), called standard IPEA (S
      IPEA), was recommended but due to its unsatisfactory performance in multiple
      metallic and organic compounds it has been questioned lately as a general
      parameter working properly for all molecules under CASPT2 study. As we are
      interested in Schiff bases of retinal, an important question emerging from this
      conflict of choice, to use or not to use S-IPEA, is whether the introduction of
      the modified zeroth-order Hamiltonian into CASPT2 ansatz does really improve
      their energetics. To achieve this goal, we assessed an impact of the IPEA shift
      value, in a range of 0-0.35 a.u., on vertical excitation energies to low-lying
      singlet states of two protonated (RPSBs) and two unprotonated (RSBs) Schiff bases
      of retinal for which experimental data in gas phase are available. In addition,
      an effect of geometry, basis set, and active space on computed VEEs is also
      reported. We find, that for these systems, the choice of S-IPEA significantly
      overestimates both S0 ->S1 and S0 ->S2 energies and the best theoretical
      estimate, in reference to the experimental data, is provided with either
      unmodified zeroth-order Hamiltonian or small value of the IPEA shift in a range
      of 0.05-0.15 a.u., depending on active space and basis set size, equilibrium
      geometry, and character of the excited state. (c) 2018 Wiley Periodicals, Inc.

PMID- 29635696
TI  - Feasibility of cathodic-anodal left ventricular stimulation for alternative
      multisite pacing.
AB  - BACKGROUND: Simultaneous cathodic-anodal capture by a bipole of a cardiac
      resynchronization therapy (CRT) left-ventricular (LV) catheter may depolarize a
      larger LV area than conventional multipoint pacing. We evaluated the feasibility
      of cathodic-anodal LV stimulation. METHODS: In 30 patients undergoing CRT with a
      quadripolar LV lead, we evaluated the cathodic and anodal capture threshold for
      each LV pole and compared QRS on electrocardiogram (ECG) during single-point
      cathodic biventricular stimulation (S-BS), multipoint BS (M-BS), and cathodic
      anodal BS (CA-BS). RESULTS: Anodal capture was obtained by three poles in 23/30
      patients, by two poles in five, and was not feasible in two. The mean single
      point anodal threshold was 3.93 V versus single-point cathodic threshold of 1.95
      V. On comparing ECGs, M-BS and CA-BS produced similar QRS wavefront activation in
      90% of patients. CONCLUSIONS: CA-BS is feasible and may be used in LV pacing to
      achieve a different wavefront of electrical activation. Further prospective
      studies are needed in order to verify the clinical impact of this kind of
      stimulation.

PMID- 29635697
TI  - 2,3,5,4'-Tetrahydroxystilbene-2-O-beta-glucoside potentiates self-renewal of
      human dental pulp stem cells via the AMPK/ERK/SIRT1 axis.
AB  - AIM: To evaluate the effect of 2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside
      (THSG) on cell proliferation and examine the mechanisms of THSG-enhanced
      proliferative potential in human dental pulp stem cells (hDPSC). METHODOLOGY:
      After treatment with THSG, hDPSC were collected. Cell viability was determined by
      MTS assay, while messenger RNA (mRNA) expressions of proliferation and stem cell
      markers were analyzed using real-time PCR. Flow cytometry was also conducted to
      analysis protein expression of stem cell markers. A colony-forming unit assay of
      hDPSC was carried out. Cellular telomerase activity was also identified using
      real-time PCR. In addition, proliferation-related proteins involved in the
      effects of THSG on hDPSC were analyzed by Western blotting. Data were analyzed
      using one-way analysis of variance and two-tailed Student's t-test. RESULTS: Cell
      viability, colony-forming rates and telomerase activities of hDPSCs were enhanced
      after THSG treatment. mRNA expressions of proliferation markers (including
      expressions of NAD+-dependent histone deacetylase sirtuin 1 (SIRT1),
      proliferating cell nuclear antigen (PCNA), cyclin D1 and ribonucleotide reductase
      subunit M2 (RRM2)) increased significantly after THSG treatment (P < 0.05).
      Treatment with THSG for 3 h significantly augmented SIRT1 protein expression (P <
      0.05). Furthermore, activities of proliferation-related proteins (including AMP
      activated protein kinase (AMPK) and extracellular signal-regulated kinase (ERK)
      had also significantly increased at 3 h (P < 0.05). After THSG treatment,
      increased gene and protein expressions of pluripotent-like stem cell markers
      (including NANOG, OCT4, and SOX2) were observed. CONCLUSIONS: 2,3,5,4'
      Tetrahydroxystilbene-2-O-beta-glucoside treatment enhanced the renewal ability
      and proliferative potential of hDPSCs via the AMPK/ERK/SIRT1 axis, which may
      provide a novel autogenic cell-based therapeutic strategy in regenerative
      dentistry.

PMID- 29635698
TI  - Detection of genetic variants between different Polish Landrace and Pulawska pigs
      by means of RNA-seq analysis.
AB  - Variant calling analysis based on RNA sequencing data provides information about
      gene variants. RNA-seq is cheaper and faster than is DNA sequencing. However, it
      requires individual hard filters during data processing due to post
      transcriptional modifications such as splicing and RNA editing. In the present
      study, RNA-seq transcriptome data on two Polish pig breeds (Pulawska, PUL, n = 8,
      and Polish Landrace, PL, n = 8) were included. The pig breeds are significantly
      different with regard to meat qualities such as texture, water exudation, growth
      traits and fat content in carcasses. A total of 2451 significant mutations were
      identified by a chi square tests, and functional analysis was carried out using
      Panther, KEGG and Kobas. Interesting missense gene variants and mutations located
      in regulatory regions were found in a few genes related to fatty acid metabolism
      and lipid storage such as ACSL5, ALDH3A2, FADS1, SCD, PLA2G12A and ATGL. A
      validation of mutational influences on pig traits was performed for ALDH3A2,
      ATGL, PLA2G12A and MYOM1 variants using association analysis including 215 pigs
      of the PL and PUL breeds. The ALDH3A2ENSSSCT00000019636.2:c.470T>C polymorphism
      was found to affect the weight of the ham and loin eye area. In turn, an
      ENSSSCT00000004091.2:c.2836G>A MYOM1 mutation, which could be implicated in
      myofibrillar network organisation, had an effect on meatiness and loin texture
      parameters. The study aimed to estimate the usefulness of RNA-seq results for a
      purpose other than differentially expressed gene analysis. The analysis performed
      indicated interesting gene variants that could be used in the future as markers
      during selection.

PMID- 29635699
TI  - Pulsed dye laser treatment of rosacea using a novel 15 mm diameter treatment
      beam.
AB  - BACKGROUND: The pulsed-dye laser has been used to treat facial redness and
      rosacea for decades. Recent advances in dye laser technology enable 50% higher
      output energies supporting 50% larger treatment areas, and beam-diameters up to
      15 mm with clinically-relevant fluences. In this study, we investigate this novel
      pulsed-dye laser using a 15 mm diameter beam for treatment of rosacea. METHODS:
      Twenty subjects with erythemato-telangiectatic rosacea were enrolled in the
      study. A total of 4 monthly treatments were administered, first treating linear
      vessels with a 3 * 10 mm elliptical beam, then diffuse redness with a 15-mm
      diameter circular beam. Blinded assessment of digital, cross-polarized
      photographs taken 2 months following the last treatment was performed using an 11
      point clearance scale. RESULTS: Nineteen subjects completed the study. Blinded
      reviewers correctly identified baseline photos in 55 out of the total of 57
      images (96.5%). The blinded reviewers scored 17 of the 19 subjects with an
      improvement greater than 40%, and 11 of the 19 subjects greater than 50%. The
      average improvement was 53.9%. Side effects were limited to mild edema, mild to
      moderate erythema, and mild to moderate bruising. CONCLUSION: This study
      demonstrates that a newly designed pulsed-dye laser having a novel 15-mm diameter
      treatment beam improves the appearance of rosacea with a favorable safety
      profile. Lasers Surg. Med. 50:808-812, 2018. (c) 2018 The Authors. Lasers in
      Surgery and Medicine Published by Wiley Periodicals, Inc.

PMID- 29635701
TI  - Complications after minimally invasive sacrocolpopexy with and without
      concomitant incontinence surgery: A National Surgical Quality Improvement Program
      (NSQIP) database study.
AB  - AIMS: To compare surgical complications for patients having minimally invasive
      sacrocolpopexy (MISCP) with concomitant incontinence procedure, to those having
      MISCP alone. METHODS: Patients undergoing MISCP with and without a concomitant
      incontinence procedure between 2006 and 2015 were identified in the American
      College of Surgeons National Surgical Quality Improvement Program database using
      Current Procedural Terminology codes. The main outcome of interest was a
      composite of surgical site infection, bleeding requiring blood transfusion,
      return to the operating room within 30 days, and surgical stay >48 h. Log
      binomial regression was used to identify independent risk factors for the outcome
      and to generate adjusted effect measures for variables of interest. RESULTS:
      Seven thousand ninety-seven women met the inclusion criteria, of which 2433 (34%)
      underwent a concomitant incontinence procedure. Patients having incontinence
      procedures were slightly older (59 +/- 11 vs 58 +/- 12, P < 0.0001) and had
      longer total operating time (225 IQR 170-267 vs 184 IQR 120-232 min, P < 0.0001).
      Pre-operative steroid use, wound class III/IV (vs I/II), and longer operative
      time were independent predictors of the composite outcome. After adjusting for
      baseline patient characteristics and co-morbidities, no association was observed
      between concomitant incontinence procedure and the composite outcome (adjusted RR
      0.87, 95%CI 0.65-1.18) but there was an increased likelihood of urinary tract
      infection (adjusted RR 2.47 95%CI 1.89-3.27). CONCLUSIONS: Despite being
      associated with a longer operative time, performing an incontinence procedure at
      the time of MSCIP was not associated with an increased risk of clinically
      important surgical complications other than urinary tract infection.

PMID- 29635700
TI  - Procalcitonin measurement to screen medullary thyroid carcinoma: A prospective
      evaluation in a series of 2705 patients with thyroid nodules.
AB  - BACKGROUND: To prospectively evaluate the role of procalcitonin (PCT) in
      screening of patients with thyroid nodules for medullary thyroid carcinoma (MTC).
      MATERIALS AND METHODS: We measured PCT in 2705 patients with thyroid nodules
      referred to our centre between January 2011 and December 2017. Those with a
      positive PCT were operated after positive confirmatory tests such as fine-needle
      aspiration, measurement of calcitonin (CT) in serum and fine-needle aspiration
      washouts or CT stimulation testing. Patients with a negative PCT were operated
      based on the results of further diagnostics. The diagnostic performance of PCT
      was evaluated, and the best cut-off level was selected by ROC curve analysis.
      RESULTS: Among 2705 patients, 9 with positive serum PCT (ie, above 0.1 MUg/L) and
      370 with negative PCT underwent thyroid surgery. MTC was histologically confirmed
      in all patients with positive PCT but not found in patients with negative PCT.
      Serum PCT levels were significantly higher in patients with MTC (median 0.64
      MUg/L, range 0.16-12.9 MUg/L) than in those without (median 0.075 MUg/L, range
      0.075-0.16 MUg/L; P < .0001). ROC curves were plotted to calculate the optimal
      PCT value separating patients with MTC from those without. The best cut-off was
      0.155 MUg/L with sensitivity, specificity, positive and negative predictive
      values as well as accuracy of 100%, 99.7%, 91.7%, 100% and 99.7%, respectively.
      Positive and negative likelihood ratios were 329 and zero, respectively.
      CONCLUSIONS: Measurement of PCT is a sensitive and accurate method for detecting
      MTC in patients with thyroid nodules and can thus be a reliable alternative to CT
      measurement.

PMID- 29635703
TI  - Fast determination of lactic, succinic, malic, tartaric, shikimic, and citric
      acids in red Vranec wines by CZE-ESI-QTOF-MS.
AB  - A fast and simple method with CZE coupled to ESI/QTOF-MS was optimized and
      validated for quantitative determination of organic acids (lactic acid, succinic
      acid, malic acid, tartaric acid, shikimic acid, and citric acid) in red wines.
      The BGE was ammonium acetate and the separation of the analytes was performed in
      a polybrene-coated capillary in the presence of EOF. The sample preparation
      included dilution and filtration of the wine. The method showed satisfactory
      performance characteristics: good linearity for each organic acid, with
      correlation coefficients ranging from r2  = 0.9902 (shikimic acid) to r2  =
      0.9990 (tartaric acid). The limit of quantification was between 0.0034 mM (for
      shikimic acid) and 0.107 mM (for citric acid), and the recovery data fell between
      95.8% (malic acid) and 102.7% (lactic acid); the total run time was less than 4
      min. The RSD values for the interday repeatability and intraday reproducibility
      were between 3.44 and 9.50%, and between 1.75 and 8.29%, respectively. Seventeen
      Macedonian red Vranec wines were studied demonstrating a wide variation in the
      organic acids' concentration, which should be most probably due to the variation
      of the climate conditions in the vine areas.

PMID- 29635702
TI  - Bowel function, sexual function, and symptoms of pelvic organ prolapse in women
      with and without urinary incontinence.
AB  - AIMS: Bowel symptoms, pelvic organ prolapse, and sexual dysfunction are common,
      but their frequency among women with lower urinary tract symptoms (LUTS) has not
      been well described. Our aims were to describe pelvic floor symptoms among women
      with and without urinary incontinence (UI) and among subtypes of UI. METHODS:
      Women with LUTS seeking care at six U.S. tertiary care centers enrolled in
      prospective cohort study were studied. At baseline, participants completed the
      Pelvic Floor Distress Inventory (PFDI-20), Pelvic Organ Prolapse/Incontinence
      Sexual Questionnaire (PISQ-IR), and PROMIS GI Diarrhea, Constipation, and Fecal
      Incontinence Scales. RESULTS: Mean age among the 510 women was 56.4 +/- 14.4
      years. Women who reported UI (n = 420) had more diarrhea and constipation
      symptoms (mean scores 49.5 vs 46.2 [P = 0.01] and 51.9 vs 48.4 [P < 0.01],
      respectively) at baseline. Among sexually active women, mean PISQ-IR subscale
      scores were lower among those with UI (condition specific: 89.8 vs 96.7, P <
      0.01; condition impact: 79.8 vs 92.5, P < 0.01). Women with mixed urinary
      incontinence (MUI) (n = 240) reported more prolapse symptoms, fecal incontinence,
      and worse sexual function compared to those with stress urinary incontinence
      (SUI) and urgency urinary incontinence (UUI). CONCLUSIONS: Women presenting with
      LUTS with UI reported significantly worse constipation, diarrhea, fecal
      incontinence, and sexual function compared to women without UI. In women with UI,
      sexual function and pelvic organ prolapse (POP) symptoms were worse in those with
      MUI compared to SUI and UUI.

PMID- 29635704
TI  - A cost-utility analysis of artificial urinary sphincter versus AdVance male sling
      in post prostatectomy stress urinary incontinence: A publicly funded health care
      perspective.
AB  - AIMS: To investigate the long-term cost-utility of the artificial urinary
      sphincter (AUS) compared with Transobturator Retroluminal Sling (AdVance) in the
      treatment of patients with severe post prostatectomy stress urinary incontinence
      (PPSUI) from a Canadian provincial health perspective. METHODS: A Markov model
      with Monte Carlo simulation was developed with a cycle length of 1 year and time
      horizon up to 10 years to estimate the incremental cost per quality-adjusted life
      years (QALYs). Patients were assigned to treatment with either AUS or an AdVance
      sling. Transition probabilities, efficacy data, and utility indices were derived
      from published literature and expert opinion. Cost data were obtained from
      provincial health care system and hospital data in 2016-Canadian dollars. The
      primary outcome was cost per quality-adjusted life year. A standard discount rate
      of 1.5% was applied annually. Probabilistic and one way deterministic sensitivity
      analyses were performed. RESULTS: AUS implantation had a 10-year mean total cost
      of $14 228 (SD +/- 3,509) for 7.58 QALYs. AdVance sling had a mean total cost $18
      938 (SD +/- 12,435) for 6.43 QALYs. The incremental cost savings of AUS over 10
      years was -$ 4710 with an added effectiveness of 1.15 QALYs. At a willingness to
      pay threshold of $50 000, AUS remained the most cost-effective option. A
      limitation of our analysis is the lack of direct long-term comparisons between
      both scenarios along with standard success definition. CONCLUSIONS: AUS
      implantation appears to be more economical treatment strategy for severe PPSUI
      compared with AdVance sling for a publicly funded health care system over a 5-
      and 10-year time horizon.

PMID- 29635705
TI  - Multiple perioral homogenous blue macules.

PMID- 29635706
TI  - Therapeutic effect of TAC-302, a cyclohexenoic fatty alcohol derivative, on
      bladder denervation-related storage and voiding dysfunctions in rats.
AB  - AIMS: To evaluate the therapeutic effect of TAC-302, a cyclohexenoic fatty
      alcohol derivative, on bladder denervation-related storage and voiding
      dysfunctions in rats with bladder outlet obstruction (BOO). METHODS: BOO was
      achieved by partial ligature of the proximal urethra in female rats. Two weeks
      later, BOO rats were divided into two groups and treated orally with vehicle or
      10 mg/kg TAC-302 twice a day for 4 weeks. Urodynamic and immunohistochemical
      evaluation of the bladder muscle layer was performed. In another study, the BOO
      rats were treated with intravenous tamsulosin at cystometry. The detrusor
      contractility in each group was evaluated using the modified Shafer's nomogram.
      RESULTS: Two weeks after BOO, the rats showed significant increases in non
      voiding contraction (NVCs) and residual urine volume (RUV) compared to the sham
      group. Moreover, 6 weeks after BOO, BOO vehicle rats showed significant increases
      in NVCs and RUV and decreases in detrusor contractility and in the nerve fiber
      density in the urinary bladder compared to the sham group. BOO-induced
      denervation of the urinary bladder was partially improved by oral treatment with
      TAC-302. Oral treatment with TAC-302 significantly reduced the amplitude and
      frequency of NVCs (P < 0.05) and increased detrusor contractility and tended to
      reduce RUV compared with the BOO vehicle group. In contrast, the intravenous
      administration of tamsulosin significantly reduced the frequency of NVCs, but not
      RUV. CONCLUSIONS: TAC-302 improved storage and voiding dysfunctions by improving
      bladder denervation and detrusor underactivity even when the treatment was
      started after storage and voiding dysfunctions had already occurred.

PMID- 29635707
TI  - Impact of heat stress during seed filling on seed quality and seed yield in
      lentil (Lens culinaris Medikus) genotypes.
AB  - BACKGROUND: Lentil, a cool-season food legume, is highly sensitive to high
      temperatures, which drastically reduce biomass and seed yield. The effects of
      heat stress on qualitative and quantitative aspects of seeds are not yet known.
      RESULTS: In this study, we assessed the effects of high temperatures on
      quantitative and qualitative aspects of seeds in a heat-tolerant (HT; FLIP2009)
      and heat-sensitive (HS; IG4242) genotypes in a controlled environment. Initially,
      the plants were raised in a natural, outdoor environment (22/10  degrees C mean
      day/night temperature, 1350 umol m-2 s-1 light intensity, 60-65% relative
      humidity) from November to mid-February until 50% flowering (114-115 days after
      sowing). After that, one set of plants was maintained in a controlled environment
      (28/23  degrees C, as mean day and night temperature, 500 umol m-2 s-1 light
      intensity, 60-65% relative humidity;control) and one set was exposed to heat
      stress (33/28  degrees C, as mean day and night temperature, 500 umol m-2 s-1
      light intensity, 60-65% relative humidity), where they remained until maturity.
      Compared to control, heat stress reduced the seed growth rate by 30-44% and the
      seed-filling duration by 5.5-8.1 days, which ultimately reduced the seed yield by
      38-58% and individual seed weights by 20-39%. Heat stress significantly damaged
      cell membranes and reduced chlorophyll concentration and fluorescence, and the
      photosynthetic rate, which was associated with a significant reduction in
      relative leaf water content. The proximate analysis of seed reserves showed that
      heat stress reduced starch (25-43%), protein (26-41%) and fat (39-57%) content,
      and increased total sugars (36-68%), relative to the controls. Heat stress also
      inhibited the accumulation of storage proteins including albumins, globulins,
      prolamins and glutelins (22-42%). Most of the amino acids decreased significantly
      under heat stress in comparison to control, whereas some, such as proline,
      followed by glycine, alanine, isoleucine, leucine and lysine, increased. Heat
      stress reduced Ca (13-28%), Fe (17-52%), P (10-54%), K (12.4-28.3%) and Zn (36
      59%) content in seeds, compared to the controls. CONCLUSIONS: High temperatures
      during seed filling are detrimental for seed yield and quality components in
      lentil genotypes, with severe impacts on heat-sensitive genotypes. (c) 2018
      Society of Chemical Industry.

PMID- 29635709
TI  - De novo overactive bladder after robot-assisted laparoscopic radical
      prostatectomy.
AB  - AIMS: To investigate storage symptoms following robot-assisted laparoscopic
      radical prostatectomy (RARP), focused on de novo overactive bladder (OAB), and to
      evaluate the factors related to de novo OAB occurrence. METHODS: We prospectively
      examined 245 patients without OAB who underwent RARP for localized prostate
      cancer. Subjective and objective symptoms in the lower urinary tract were
      evaluated before and after surgery. At 3 months after RARP, the patients were
      divided into two groups: patients with de novo OAB (de novo OAB group) and those
      without OAB (OAB-free group). We compared the operative and urodynamic parameters
      between both groups and evaluated the factors related to OAB. RESULTS: De novo
      OAB was observed in 37.8% (87/230) of patients. Post-operative continence rate
      was significantly higher in the OAB-free group (79.7%) than in the de novo OAB
      group (8.0%). Although the International Prostate Symptom Score (IPSS) and
      Overactive Bladder Symptom Score (OABSS) in the de novo OAB group significantly
      deteriorated from 9.7 to 14.1 and from 2.4 to 8.3, respectively, no corresponding
      significant changes occurred in the OAB-free group. Additionally, there was a
      significant difference in pre-operative IPSS-QOL score, continence rate, pre-and
      post-operative maximum urethral closing pressure (MUCP), and post-operative
      functional profile length (FPL) between both groups. Multivariable logistic
      regression analysis showed pre-operative IPSS-QOL score and post-operative MUCP
      were significant predictive factors for de novo OAB. CONCLUSIONS: The incidence
      rate of de novo OAB after RARP was about 40%, and seemed unexpectedly high.
      Decreased urethral function was significantly related to de novo OAB after
      surgery.

PMID- 29635708
TI  - Human CD31 on porcine cells suppress xenogeneic neutrophil-mediated cytotoxicity
      via the inhibition of NETosis.
AB  - BACKGROUND: Xenotransplantation is one of the promising strategies for overcoming
      the shortage of organs available for transplant. However, many immunological
      obstructions need to be overcome for practical use. Increasing evidence suggests
      that neutrophils contribute to xenogeneic cellular rejection. Neutrophils are
      regulated by activation and inhibitory signals to induce appropriate immune
      reactions and to avoid unnecessary immune reactivity. Therefore, we hypothesized
      that the development of neutrophil-targeted therapies may have the potential for
      increased graft survival in xenotransplantation. METHODS: A plasmid containing a
      cDNA insert encoding the human CD31 gene was transfected into swine endothelial
      cells (SEC). HL-60 cells were differentiated into neutrophil-like cells by
      culturing them in the presence of 1.3% dimethyl sulfoxide for 48 hours. The
      cytotoxicity of the differentiated HL-60 cells (dHL-60) and peripheral blood
      derived neutrophils was evaluated by WST-8 assays. To investigate the mechanism
      responsible for hCD31-induced immunosuppression, citrullinated histone 3 (cit-H3)
      and phosphorylation of SHP-1 were detected by a cit-H3 enzyme-linked
      immunosorbent assay (ELISA) and Western blotting, respectively. RESULTS: A
      significant decrease in dHL-60 and neutrophil-mediated cytotoxicity in SEC/hCD31
      compared with SEC was seen, as evidenced by a cytotoxicity assay. Furthermore,
      the suppression of NETosis and the induction of SHP-1 phosphorylation in
      neutrophils that had been co-cultured with SEC/CD31 were confirmed by cit-H3
      ELISA and Western blotting with an anti-phosphorylated SHP-1. CONCLUSION: These
      data suggest that human CD31 suppresses neutrophil-mediated xenogenic
      cytotoxicity via the inhibition of NETosis. As CD31 is widely expressed in a
      variety of inflammatory cells, human CD31-induced suppression may cover the
      entire xenogeneic cellular rejection, thus making the generation of human CD31
      transgenic pigs very attractive for use in xenografts.

PMID- 29635710
TI  - Antibacterial Activity of Constituents from Mangosteen Garcinia mangostana Fruit
      Pericarp against Several Channel Catfish Pathogens.
AB  - Bacterial diseases cause major financial damage to the producers of Channel
      Catfish Ictalurus punctatus in the southeastern USA. The two most common
      bacterial diseases among pond-raised Channel Catfish are enteric septicemia of
      catfish, caused by the gram-negative bacterium Edwardsiella ictaluri, and
      columnaris disease, caused by the rod-shaped, gram-negative bacterium
      Flavobacterium columnare. Streptococcosis is another, less-common bacterial
      disease in catfish and is caused by the gram-positive coccus Streptococcus iniae.
      Catfish farmers typically rely on commercial antibiotics and other chemicals to
      prevent the economic damage from these diseases. Environmentally benign and
      efficacious alternatives to the currently used antibiotics and chemicals will
      tremendously help the catfish aquaculture industry. As part of our ongoing
      efforts in the search for such novel compounds, we investigated ethyl acetate and
      methanol extracts of mangosteen Garcinia mangostana fruit pericarp via bioassay
      guided fractionation. Gamma-mangostin (gamma-mangostin) was isolated and
      identified as the most promising active metabolite against F. columnare. One of
      the constituents in the mangosteen fruit pericarp, alpha-mangostin (alpha
      mangostin), is the major xanthone; alpha-mangostin was found to be 10-fold less
      active than gamma-mangostin when minimum inhibitory concentration values were
      compared.

PMID- 29635711
TI  - Genetics of gallstone disease.
AB  - BACKGROUND: Gallstone disease (GD) belongs to the most frequent disorders in
      gastroenterology and causes high costs in our health-care systems. Gallstones are
      uncommon in children but frequent in adults, in particular in women, and are
      triggered by exogenous risk factors. Here, we summarize the current knowledge
      concerning the contribution of inherited predisposition to gallstone risk.
      DESIGN: In this review, we present the current data and recent research on the
      genetics of gallstone disease. RESULTS: Several GD-predisposing gene variants
      have been reported, with most prominent effects being conferred by a common
      variant (p.D19H) of the hepatic and intestinal cholesterol transporter ABCG5/G8.
      A smaller group of patients might develop gallstones primarily due low
      phosphatidylcholine concentrations in bile as a result of loss-of-function
      mutations of the ABCB4 transporter (low phospholipid-associated cholelithiasis
      syndrome). Regardless of the origin, the risk factors for gallstones lead to the
      supersaturation of bile with insoluble compounds, in particular cholesterol. As
      result, cholesterol stones develop and present the most frequent type of
      gallstones. Laparoscopic cholecystectomy with low morbidity and mortality is
      currently the most common and effective method for the therapy of symptomatic
      gallbladder stones. CONCLUSIONS: Gallstone disease represents a multifactorial
      condition and previous studies have identified the major genetic contributors to
      gallstone formation. The increasing knowledge about the pathomechanisms of
      hepatobiliary metabolism and GD as well as the identification of additional risk
      factors might help to overcome the current invasive therapy by specific lifestyle
      intervention and precise molecular treatment.

PMID- 29635712
TI  - Anaesthetic efficacy of articaine versus lidocaine in children's dentistry: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Over the last few years, numerous reviews and studies have awarded
      articaine hydrochloride local anaesthetic (LA) a superior reputation, with
      outcomes of different studies demonstrating a general tendency for articaine
      hydrochloride to outperform lidocaine hydrochloride for dental treatment.
      Nevertheless, there seems to be no clear agreement on which LA solution is more
      efficacious in dental treatment for children. There is no previous publication
      systematically reviewing and summarising the current best evidence with respect
      to the success rates of LA solutions in children. AIMS: To evaluate the available
      evidence on the efficacy of lidocaine and articaine, used in paediatric
      dentistry. DESIGN: A systematic search was conducted on Cochrane CENTRAL Register
      of Controlled Trials, MEDLINE (OVID; 1950 to June 2017), Cumulative Index to
      Nursing and Allied Health Literature (CINAHL; EBSCOhost; 1982 to June 2017),
      EMBASE (OVID; 1980 to June 2017), SCI-EXPANDED (ISI Web of Knowledge; 1900 to
      June 2017), key journals, and previous review bibliographies through June 2017.
      Original research studies that compared articaine with lidocaine for dental
      treatment in children were included. Methodological quality assessment and
      assessment of risk of bias were carried out for each of the included studies.
      RESULTS: Electronic searching identified 525 publications. Following the primary
      and secondary assessment process, six randomised controlled trials (RCT) were
      included in the final analysis. There was no difference between patient self
      reported pain between articaine and lidocaine during treatment procedures (SMD =
      0.06, P-value = 0.614), and no difference in the occurrence of adverse events
      between articaine and lidocaine injections following treatment in paediatric
      patients (RR = 1.10, P-value = 0.863). Yet, patients reported significantly less
      pain post-procedure following articaine injections (SMD = 0.37, P-value = 0.013).
      Substantial heterogeneity was noted in the reporting of outcomes among studies,
      with the overall quality of majority of studies being at high risk of bias.
      CONCLUSIONS: There is low quality evidence suggesting that both articaine as
      infiltration and lidocaine IAD nerve blocks presented the same efficacy when used
      for routine dental treatments, with no difference between patient self-reported
      pain between articaine and lidocaine during treatment procedures. Yet,
      significantly less pain post-procedure was reported following articaine
      injections. There was no difference in the occurrence of adverse events between
      articaine and lidocaine injections following treatment in paediatric patients.

PMID- 29635713
TI  - A lifeSPANS approach: Addressing child obesity in Australia.

PMID- 29635714
TI  - Pallidal Deep Brain Stimulation in Patients With Chorea-Acanthocytosis.
AB  - INTRODUCTION: Chorea-acanthocytosis (ChAc) is an autosomal recessive hereditary
      disorder caused by the mutation of gene VPS13A. Deep brain stimulation of ChAc
      has made substantial progress in the recent decades. However, the reports were
      scattered across centers and performed by different neurosurgeons. Here, we
      report a case series consisting of six patients diagnosed with ChAc, receiving
      bilateral high-frequency stimulation of globus pallidus internus (GPi) in a
      single center. METHODS: We report six consecutive patients diagnosed with ChAc
      and present a review of the literature. All patients received neurological
      evaluations using the Unified Huntington's Disease Rating Scale (UHDRS) motor
      score before surgery and during clinical follow-ups. One patient was observed
      over six months, while five patients were seen over 12 months. RESULTS: All
      patients underwent high-frequency stimulation ranging from 130 Hz to 175 Hz. In
      the follow-up period, a general trend was found toward higher amplitude and
      broader pulse widths, with a mean current range of 2.08 mA to 3.06 mA and a mean
      pulse width range of 75 MUsec to 98 MUsec. On preoperative evaluation, the mean
      UHDRS motor score was 35.7 +/- 16.3 and the chorea subscore was 11.3 +/- 4.7. At
      the three-month postoperative follow-up, both UHDRS motor score (13.5 +/- 5.8)
      and chorea subscore (3.0 +/- 1.2) reached valley values. Thereafter, the UHDRS
      motor score and chorea subscore showed a gradual rise, reaching 19.2 +/- 5.9 and
      4.8 +/- 1.7, respectively, at the 12-month follow-up. In addition, adverse events
      were also seen. Patient 1 developed dysarthria six months after surgery, whereas
      Patient 6 had a generalized tonic-clonic seizure attack one day after surgery
      CONCLUSION: High frequency stimulation of the GPi is an effective and safe
      modality for the treatment of ChAc, with both rapid symptomatic improvements and
      steady chronic outcomes.

PMID- 29635715
TI  - In vivo evaluation of garlic (Allium sativum) supplementation to rice straw-based
      diet on mitigation of CH4 and CO2 emissions and blood profiles using crossbreed
      rams.
AB  - BACKGROUND: Two experiments were implemented using three cannulated crossbreed
      rams (Corriedale * Suffolk) fed rice straw-based diet. In vivo evaluation of
      garlic powder (GP) supplementation to rice straw-based diet on CH4 and CO2
      emissions and blood profiles of the rams (body weight = 52 +/- 3 kg) was
      performed. The design was a triplicate 3 * 3 Latin square. Groups were the
      control (no GP) and two GP groups, which were given supplementation for 0.1
      (GP0.1) and 0.5% (GP0.5) of concentrate. The differences between two experiments
      were data missing of GP0.1 and uncontrolled environment in Experiment 1. Blood
      profiles were added in Experiment 2. RESULTS: In Experiment 1, supplementation of
      GP to the rams reduced CH4 production significantly (P < 0.05) by 38%. Dry matter
      intake was not different among the groups in both experiments. In Experiment 2,
      CH4 was lower in the GP0.5 group than the control group by 7%, whereas CO2 showed
      no difference among the groups. Serum glutamic oxaloacetic transaminase was
      significantly (P > 0.05) lower in the GP0.5 group than the control group, whereas
      glutamic pyruvic transaminase, total protein, urea N, total cholesterol, low
      density lipoprotein, calcium, phosphorus, magnesium and non-esterified fatty
      acids were not significantly (P > 0.05) different. CONCLUSIONS: GP
      supplementation, particularly GP0.5, decreases CH4 emissions in rams fed rice
      straw-based diets. (c) 2018 Society of Chemical Industry.

PMID- 29635716
TI  - Beta-3 adrenoceptor expression in the uterosacral ligament in the postmenopausal
      women with pelvic organ prolapse.
AB  - AIMS: beta3-adrenoceptor (beta3-AR) agonist is known to relax the detrusor
      muscles. Considering that both pelvic organ prolapse (POP) and overactive-bladder
      (OAB) are frequently seen in the elderly population, the effect of beta3-AR
      agonist on the pelvic floor tissues should be investigated. As a first step, this
      pilot, experimental, and descriptive study was designed to investigate the
      presence of beta3-AR expression in the uterosacral-ligaments (USLs) in
      postmenopausal (PMP) women with POP. METHODS: After informed consent, PMP women
      undergoing hysterectomy for POP were recruited for the intraoperative collection
      of distal USL between 5/2016 and 8/2016. H&E analysis for the USLs and
      immunohistochemistry (IHC) analysis for beta3-AR and alpha-actin smooth muscle
      (SM) were carried out. Tissue composition and percentage of beta3-AR expression
      in the USLs were subjectively measured and the staining results were expressed as
      descriptive analysis. RESULTS: Total 11 USL specimens were collected and nine
      specimens were included for the final analysis (one specimen: used for antibody
      concentration adjustment and one specimen: failed proper staining). Under high
      power-field, the USLs were composed of SM cells (81.5 +/- 7.47%) and connective
      tissues (16.5 +/- 7.9%). On IHC analysis, six out of nine specimens expressed
      beta3-AR with a different level of expression in SM cells in the USLs.
      CONCLUSIONS: The majority of distal USLs were composed of SM cells. beta3-ARs are
      expressed in 67% of the study specimens. Considering that both POP and OAB are
      frequently seen in the elderly population, the effect of beta3-AR agonist on the
      pelvic floor tissues should be investigated further.

PMID- 29635717
TI  - Endoscopy screening effect on stage distributions of esophageal cancer: A cluster
      randomized cohort study in China.
AB  - Efficacy of endoscopic screening for esophageal cancer is not sufficiently
      definitive and lacks randomized controlled trial evidence. The present study
      proved short-term screening efficacy through describing and comparing disease
      stage distributions of intervention and control populations. Villages from
      Linzhou and Cixian were cluster randomly allocated to the intervention or to the
      control group and the target population of 52 729 and 43 068 individuals was 40
      69 years old, respectively, and the actual enrolled numbers were 18 316 and 21
      178, respectively. TNM stage information and study-defined stage information of
      esophageal cases from 2012 to 2016 were collected. Stage distributions were
      compared between the intervention and control groups in the total target
      population, as well as in the subgroup populations in terms of enrolment and
      before or after intervention. There were a total of 199 and 141 esophageal cancer
      cases in the intervention and control groups, respectively. For the target
      population, distributions of TNM stage were borderline significant between the
      two groups after intervention (P = .093). However, subgroup analysis of the
      enrolled population during the after-intervention period had statistical
      significance for both TNM and study-defined stage. Natural TNM stage
      distributions were approximately 32%, 41%, 24% and 3% for stages I to IV vs 71%,
      19%, 7% and 3% in the intervention population. The natural study-defined stage
      distributions from early, middle to advanced stages were approximately 18%, 49%
      and 33% vs 59%, 33% and 8%. Early-stage esophageal cancer cases accounted for a
      higher proportion after endoscopy screening, and the efficacy in the target
      population depends on the intervention compliance.

PMID- 29635718
TI  - A Beautiful Life in a Vibrant Yet Vulnerable City.

PMID- 29635719
TI  - Response to the letter to the Editor: Comments on marital status is a prognostic
      factor in amyotrophic lateral sclerosis. Safiri S et al.

PMID- 29635720
TI  - Comments on marital status is a prognostic factor in amyotrophic lateral
      sclerosis.

PMID- 29635721
TI  - Phenotype and genotype of muscle ryanodine receptor rhabdomyolysis-myalgia
      syndrome.
AB  - OBJECTIVES: Rhabdomyolysis and myalgia are common conditions, and mutation in the
      ryanodine receptor 1 gene (RYR1) is suggested to be a common cause. Due to the
      large size of RYR1, however, sequencing has not been widely accessible before the
      recent advent of next-generation sequencing technology and limited phenotypic
      descriptions are therefore available. MATERIAL & METHODS: We present the medical
      history, clinical and ancillary findings of patients with RYR1 mutations and
      rhabdomyolysis and myalgia identified in Denmark, France and The Netherlands.
      RESULTS: Twenty-two patients with recurrent rhabdomyolysis (CK > 10 000) or
      myalgia with hyperCKemia (>1.5 * ULN) and a RYR1 mutation were identified. One
      had mild wasting of the quadriceps muscle, but none had fixed weakness. Symptoms
      varied from being restricted to intense exercise to limiting ADL function. One
      patient developed transient kidney failure during rhabdomyolysis. Two received
      immunosuppressants on suspicion of myositis. None had episodes of malignant
      hyperthermia. Muscle biopsies were normal, but CT/MRI showed muscle hypertrophy
      in most. Delay from first symptom to diagnosis was 12 years on average. Fifteen
      different dominantly inherited mutations were identified. Ten were previously
      described as pathogenic and 5 were novel, but rare/absent from the background
      population, and predicted to be pathogenic by in silico analyses. Ten of the
      mutations were reported to give malignant hyperthermia susceptibility.
      CONCLUSION: Mutations in RYR1 should be considered as a significant cause of
      rhabdomyolysis and myalgia syndrome in patients with the characteristic
      combination of rhabdomyolysis, myalgia and cramps, creatine kinase elevation, no
      weakness and often muscle hypertrophy.

PMID- 29635722
TI  - Short-term swimming exercise attenuates the sensitization of dorsal horn neurons
      in rats with NGF-induced low back pain.
AB  - BACKGROUND: Physical exercise has been shown to be an effective therapy for non
      specific low back pain. The study investigated if swimming exercise is a means to
      reduce the spinal sensitization in an animal model of non-specific low back pain.
      METHODS: In deeply anesthetized rats, dorsal horn neurons were recorded in spinal
      segment L2. To induce sensitization of dorsal horn neurons, two injections of
      nerve growth factor were made into the lumbar multifidus muscle at an interval of
      5 days. Swimming exercise for 30 min was performed on the 5 days between both NGF
      injections. A control group received the NGF injections without exercise
      treatment. RESULTS: Swimming exercise caused a significant decrease in the NGF
      induced hyperexcitability of dorsal horn neurons. Compared to control, the
      proportion of neurons with input from deep somatic tissues and of convergent
      neurons with input from at least two types of different tissues decreased
      significantly (50% vs. 25% and 37% vs. 15%; both p < 0.05). Swimming exercise
      also reduced the NGF-induced increase in neuronal resting activity. Both the
      proportion of active neurons and the mean discharge frequency of all neurons
      decreased significantly (60%, 76.3 +/- 23.1 imp/min; vs. 25%, 51.7 +/- 35.1
      imp/min; both p < 0.01). CONCLUSIONS: In our animal model of low back pain, short
      term swimming exercise effectively reduced the latent sensitization of spinal
      dorsal horn neurons. Swimming exercise decreased the hyperexcitability of the
      neurons to low back input and lowered the resting activity of sensitized neurons.
      SIGNIFICANCE: Physical exercise is a common treatment for low back pain. The
      possible mechanisms underlying the effects of exercise are probably multifold.
      This work shows that swimming exercise prevents sensitization of dorsal horn
      neurons, which may be one mechanism for the positive effects of exercise.

PMID- 29635723
TI  - Successful treatment of chronic norovirus gastroenteritis with nitazoxanide in a
      pediatric kidney transplant recipient.
AB  - Uncontrolled studies suggest a benefit of nitazoxanide for the treatment of
      norovirus gastroenteritis in immunocompromised individuals. Here, we report the
      use of nitazoxanide in a 13-year-old male kidney transplant recipient who
      developed intractable norovirus gastroenteritis. Reduction of immunosuppression
      was not possible due to refractory TCMR. Administration of oral immunoglobulin
      and switching from tacrolimus to sirolimus failed to produce a meaningful
      clinical response. Treatment with a 14-day course of nitazoxanide resulted in
      prompt resolution of diarrhea as well as clearance of norovirus from the stool
      despite intense immunosuppression. Nitazoxanide may be considered as an option
      for the treatment of intractable norovirus gastroenteritis in pediatric
      transplant patients when reduced immunosuppression is not feasible or other
      treatment options have failed. Further studies to evaluate the safety and
      effectiveness of nitazoxanide in immunocompromised children are needed.

PMID- 29635724
TI  - Cerebellar high-grade astrocytoma with IDH mutations in the elderly: A report of
      two cases.
AB  - Cerebellar high-grade gliomas are rare, and likely to affect younger patients
      compared with those of cerebral origin. Recent genetic analyses have revealed
      that isocitrate dehydrogenase (IDH) 1/2 mutations are rare in infratentorial
      gliomas. In this paper, we report two elderly cases of IDH-mutated cerebellar
      high-grade glioma with unusual histological features and uncommon patient ages.
      One case was an 83-year-old man, whose tumor was predominantly composed of
      densely packed round-to-polygonal epithelioid cells. The other was a 75-year-old
      woman's high-grade astrocytoma characterized by cord-like structures and the
      perivascular papillary arrangements with varying amounts of myxoid matrix. The
      former harbored IDH1 R132H mutation, whereas the latter had IDH2 R172K mutation.
      According to our literature review, eight cases of IDH-mutated infratentorial
      gliomas including the present cases have been reported, and four had mutations
      other than IDH1 R132H. Moreover, we herein report the first elderly case of IDH2
      mutation. Although the number is limited, IDH-mutant infratentorial diffuse
      gliomas may have clinical, histological and genetic features different from
      supratentorial cases.

PMID- 29635725
TI  - Sustainable Synthesis of Co@NC Core Shell Nanostructures from Metal Organic
      Frameworks via Mechanochemical Coordination Self-Assembly: An Efficient
      Electrocatalyst for Oxygen Reduction Reaction.
AB  - Herein, a new type of cobalt encapsulated nitrogen-doped carbon (Co@NC)
      nanostructure employing Znx Co1-x (C3 H4 N2 ) metal-organic framework (MOF) as
      precursor is developed, by a simple, ecofriendly, solvent-free approach that
      utilizes a mechanochemical coordination self-assembly strategy. Possible
      evolution of Znx Co1-x (C3 H4 N2 ) MOF structures and their conversion to Co@NC
      nanostructures is established from an X-ray diffraction technique and
      transmission electron microscopy analysis, which reveal that MOF-derived Co@NC
      core-shell nanostructures are well ordered and highly crystalline in nature.
      Co@NC-MOF core-shell nanostructures show excellent catalytic activity for the
      oxygen reduction reaction (ORR), with onset potential of 0.97 V and half-wave
      potential of 0.88 V versus relative hydrogen electrode in alkaline electrolyte,
      and excellent durability with zero degradation after 5000 potential cycles;
      whereas under similar experimental conditions, the commonly utilized Pt/C
      electrocatalyst degrades. The Co@NC-MOF electrocatalyst also shows excellent
      tolerance to methanol, unlike the Pt/C electrocatalyst. X-ray photoelectron
      spectroscopy (XPS) analysis shows the presence of ORR active pyridinic-N and
      graphitic-N species, along with CoNx ?Cy and Co?Nx ORR active (M-N-C) sites.
      Enhanced electron transfer kinetics from nitrogen-doped carbon shell to core Co
      nanoparticles, the existence of M-N-C active sites, and protective NC shells are
      responsible for high ORR activity and durability of the Co@NC-MOF
      electrocatalyst.

PMID- 29635726
TI  - Synthesis, Structure, and Anion Binding Properties of Electron-Deficient
      Tetrahomocorona[4]arenes: Shape Selectivity in Anion-pi Interactions.
AB  - Tetrahomocorona[2]arene[2]tetrazines were constructed by means of a fragment
      coupling strategy based on nucleophilic aromatic substitution reaction starting
      from 3,6-dichlorotetrazine and o-, m-, and p-bis(hydroxymethyl)benzenes. The
      unprecedented macrocycles gave rectangular box-like cavities with tunable cavity
      sizes and deficient electronic properties depending on the substitution pattern
      of phenylene. Due to anion-pi interactions, they formed complexes selectively
      with azide and thiocyanate owing to complementary shapes between host and guest.

PMID- 29635727
TI  - Reverse Solvatochromism of Imine Dyes Comprised of 5-Nitrofuran-2-yl or 5
      Nitrothiophen-2-yl as Electron Acceptor and Phenolate as Electron Donor.
AB  - Eight compounds with phenols as electron-donating groups and 5-nitrothiophen-2-yl
      or 5-nitrofuran-2-yl acceptor moieties in their molecular structures were
      synthesized. The crystalline structures of six compounds were obtained. Their
      corresponding phenolate dyes were studied in 29 solvents and the data showed that
      in all cases a reverse solvatochromism occurred. The results are explained in
      terms of the ability of the medium to stabilize the electronic ground and excited
      states of the probes to different extents. The frontier molecular orbitals were
      analyzed for the protonated and deprotonated forms of the compounds. The
      calculated geometries are in agreement with the X-ray structures determined for
      the compounds and it was verified that after their deprotonation an increase in
      the electron delocalization occurs. Radial distribution functions were calculated
      for the dyes in water and n-hexane to analyze different solvation patterns
      resulting from the interaction of the solvents with the dyes. Data obtained by
      using the Catalan multiparameter equation revealed that the medium acidity is
      responsible for hypsochromic shifts, whereas the solvent basicity,
      polarizability, and dipolarity contributed to bathochromic shifts of the
      solvatochromic band of these dyes. Two model "hybrid cyanine" dyes were used in
      the design of simple experiments to demonstrate that the solvatochromic behavior
      of these dyes in solution can be tuned with careful consideration of the
      properties of the medium.

PMID- 29635728
TI  - Characteristics of deposits and pump exchange in the Berlin Heart EXCOR
      ventricular assist device: Experience with 67 cases.
AB  - Pump exchanges are frequently required in the Berlin Heart EXCOR VAD. We intended
      to describe the characteristics of pump deposits in a larger patient series and
      evaluate if changes in our exchange procedure over time have led to increased
      complications. We reviewed all EXCOR pump exchanges in our institution from July
      2004 to October 2014. We gathered data on size and location of pump deposits and
      exchange procedures. EXCOR devices were implanted in 38 children. Support was
      LVAD only in 22, BiVAD in 13, and SVAD in 3 cases. Sixty-seven pumps were
      exchanged. The incidence of pump exchanges per month was higher for smaller pumps
      and for RVADs vs LVADs. Indications were visible pump deposit in 55, stroke
      without visible deposit in 5, incorporation of membrane oxygenator in 3, pump
      size change in 2, and sepsis in 1 case, respectively. Deposits were located in
      the outflow valve in 73%, inflow valve in 22%, pump body in 3%, and outflow
      cannula in 3%. EXCOR pumps are predominantly exchanged for deposits, which are
      most frequently located in the outflow valves. The procedure is now carried out
      without sedation at the bedside. No major complications were observed during
      exchanges.

PMID- 29635729
TI  - Novel modification of the Reported Edmonton Frail Scale.
AB  - OBJECTIVES: The Reported Edmonton Frail Scale (REFS) uses clock drawing as a
      measure of cognition. However, many patients in the acute hospital setting
      present with an inability to clock-draw. We considered an alternative method for
      assessing cognition based on a history of cognitive impairment. METHODS: We
      created a modified version of the REFS (mod-REFS), utilising the same domains as
      the REFS, in which a screening question of cognition substitutes the clock
      drawing task. Data were collected from a prospective cohort study. RESULTS: Of
      181 participants, frailty measured with either the REFS or the mod-REFS found
      equivalence. A comparison between clock drawing and cognitive question scores
      demonstrated a complete agreement for 152 patients (84%), a reduction in
      cognition score for 25 (14%) and an increase for 4 (2%). CONCLUSION: We suggest
      the mod-REFS will improve the frailty assessment in the acute hospital setting,
      overcoming the limitations associated with clock drawing.

PMID- 29635730
TI  - Phase-Engineered PtSe2 -Layered Films by a Plasma-Assisted Selenization Process
      toward All PtSe2 -Based Field Effect Transistor to Highly Sensitive, Flexible,
      and Wide-Spectrum Photoresponse Photodetectors.
AB  - The formation of PtSe2 -layered films is reported in a large area by the direct
      plasma-assisted selenization of Pt films at a low temperature, where
      temperatures, as low as 100  degrees C at the applied plasma power of 400 W can
      be achieved. As the thickness of the Pt film exceeds 5 nm, the PtSe2 -layered
      film (five monolayers) exhibits a metallic behavior. A clear p-type
      semiconducting behavior of the PtSe2 -layered film (~trilayers) is observed with
      the average field effective mobility of 0.7 cm2 V-1 s-1 from back-gated
      transistor measurements as the thickness of the Pt film reaches below 2.5 nm. A
      full PtSe2 field effect transistor is demonstrated where the thinner PtSe2 ,
      exhibiting a semiconducting behavior, is used as the channel material, and the
      thicker PtSe2 , exhibiting a metallic behavior, is used as an electrode, yielding
      an ohmic contact. Furthermore, photodetectors using a few PtSe2 -layered films as
      an adsorption layer synthesized at the low temperature on a flexible substrate
      exhibit a wide range of absorption and photoresponse with the highest
      photocurrent of 9 uA under the laser wavelength of 408 nm. In addition, the
      device can maintain a high photoresponse under a large bending stress and 1000
      bending cycles.

PMID- 29635731
TI  - Chemiluminescent Probes for Activity-Based Sensing of Formaldehyde Released from
      Folate Degradation in Living Mice.
AB  - Formaldehyde (FA) is a common environmental toxin that is also produced naturally
      in the body through a wide range of metabolic and epigenetic processes,
      motivating the development of new technologies to monitor this reactive carbonyl
      species (RCS) in living systems. Herein, we report a pair of first-generation
      chemiluminescent probes for selective formaldehyde detection. Caging phenoxy
      dioxetane scaffolds bearing different electron-withdrawing groups with a general
      2-aza-Cope reactive formaldehyde trigger provides chemiluminescent formaldehyde
      probes 540 and 700 (CFAP540 and CFAP700) for visible and near-IR detection of FA
      in living cells and mice, respectively. In particular, CFAP700 is capable of
      visualizing FA release derived from endogenous folate metabolism, providing a
      starting point for the use of CFAPs and related chemical tools to probe FA
      physiology and pathology, as well as for the development of a broader palette of
      chemiluminescent activity-based sensing (ABS) probes that can be employed from in
      vitro biochemical to cell to animal models.

PMID- 29635732
TI  - Breakthrough cancer pain: The importance of the right treatment at the right
      time.
AB  - BACKGROUND: Confusion remains over the definition of breakthrough cancer pain
      (BTcP) potentially leading to delayed diagnosis and treatment. METHODS: An on
      line survey was conducted in four EU countries among relevant healthcare
      professionals and cancer patients diagnosed with BTcP. The roles of healthcare
      professionals (HCPs) were examined and their knowledge and use of available
      medications recorded. Patients were questioned on how BTcP affected their lives
      and on the medications they had received/were receiving. RESULTS: There was a
      'time lag' of 58 and 13 weeks in Germany and Spain respectively between the
      initial diagnosis of BTcP and its treatment. Four in ten oncologists across the
      four countries considered themselves not fully confident in their choice of the
      appropriate therapy. A quarter of patients in Germany, Italy and Spain and four
      in ten in France were treated only with increased dosages of the therapy already
      prescribed for their background pain - often morphine. Almost another quarter
      received morphine in addition to their treatment for background pain. Oncologists
      indicated a need for faster-acting treatments revealing a potential lack of
      awareness of rapid onset oral opioids and patients expressed a desire for more
      effective pain relief and better psychological support. CONCLUSIONS: There is a
      need for a universal definition of BTcP to facilitate earlier and more accurate
      diagnosis. It is essential that BTcP is treated immediately on diagnosis with
      therapies that more closely mirror its temporal characteristics to ensure that
      patients' desire for more effective pain relief is fulfilled. SIGNIFICANCE: Many
      cancer patients suffered episodes of BTcP needlessly over many months due to
      missed diagnosis. Even after diagnosis, many physicians were not fully confident
      in their choice of 'rescue' therapy which perhaps is not surprising given the
      very low level of awareness of treatment guidelines, both national and
      international.

PMID- 29635733
TI  - Renal impairment markers in type 2 diabetes patients with different types of
      hyperuricemia.
AB  - AIMS/INTRODUCTION: Hyperuricemia (HUA) occurs because of decreased excretion of
      uric acid, increased synthesis of uric acid or a combination of both mechanisms.
      The proportions of these three types of HUA in type 2 diabetes patients are not
      known. In the mean time, we assume that different types of HUA might manifest
      with different renal damage, even in patients with normal renal filtration
      function. MATERIALS AND METHODS: We included 435 inpatients with type 2 diabetes
      at the Metabolic Disease Hospital of Tianjin Medical University from 2015 to
      2016. Based on the clearance of uric acid, 90 patients with HUA were divided into
      three types: synthesis-increased HUA, excretion-decreased HUA and mixed type of
      HUA. RESULTS: Patients with the mixed type of HUA had the severest kidney injury
      manifested by a high level of 24 h urinary microalbumin, urinary immunoglobulin
      G, transferrin, alpha-galactosidase and beta2-microglobulin compared with the
      normal uric acid group. Urinary immunoglobulin G, transferrin and alpha
      galactosidase were also increased in patients with synthesis-increased HUA
      compared with the normal uric acid group. Patients with excretion-decreased HUA
      did not have an increased level of renal impairment markers; however, these
      patients had an increased body mass index, which might cause dysfunction of
      kidney excretion. CONCLUSIONS: Excretion-decreased HUA is a more common type of
      HUA in type 2 diabetes patients that might be caused by dysfunction of tubular
      excretion instead of structural damage. The mixed type of HUA patients had the
      severest kidney glomerular and tubular damage compared with the normal uric acid
      group. Clinically, different types of hyperuricemia should be given
      individualized treatment according to their own characteristics.

PMID- 29635734
TI  - An edge-readout, multilayer detector for positron emission tomography.
AB  - PURPOSE: We present a novel gamma-ray-detector design based on total internal
      reflection (TIR) of scintillation photons within a crystal that addresses many
      limitations of traditional PET detectors. Our approach has appealing features,
      including submillimeter lateral resolution, DOI positioning from layer thickness,
      and excellent energy resolution. The design places light sensors on the edges of
      a stack of scintillator slabs separated by small air gaps and exploits the
      phenomenon that more than 80% of scintillation light emitted during a gamma-ray
      event reaches the edges of a thin crystal with polished faces due to TIR. Gamma
      ray stopping power is achieved by stacking multiple layers, and DOI is determined
      by which layer the gamma ray interacts in. METHOD: The concept of edge readouts
      of a thin slab was verified by Monte Carlo simulation of scintillation light
      transport. An LYSO crystal of dimensions 50.8 mm * 50.8 mm * 3.0 mm was modeled
      with five rectangular SiPMs placed along each edge face. The mean-detector
      response functions (MDRFs) were calculated by simulating signals from 511 keV
      gamma-ray interactions in a grid of locations. Simulations were carried out to
      study the influence of choice of scintillator material and dimensions, gamma-ray
      photon energies, introduction of laser or mechanically induced optical barriers
      (LIOBs, MIOBs), and refractive indices of optical-coupling media and SiPM
      windows. We also analyzed timing performance including influence of gamma-ray
      interaction position and presence of optical barriers. We also modeled and built
      a prototype detector, a 27.4 mm * 27.4 mm * 3.0 mm CsI(Tl) crystal with 4 SiPMs
      per edge to experimentally validate the results predicted by the simulations. The
      prototype detector used CsI(Tl) crystals from Proteus outfitted with 16 Hamamatsu
      model S13360-6050PE MPPCs read out by an AiT-16-channel readout. The MDRFs were
      measured by scanning the detector with a collimated beam of 662-keV photons from
      a 137 Cs source. The spatial resolution was experimentally determined by imaging
      a tungsten slit that created a beam of 0.44 mm (FWHM) width normal to the
      detector surface. The energy resolution was evaluated by analyzing list-mode data
      from flood illumination by the 137 Cs source. RESULT: We find that in a block
      detector-sized LYSO layer read out by five SiPMs per edge, illuminated by 511-keV
      photons, the average resolution is 1.49 mm (FWHM). With the introduction of
      optical barriers, average spatial resolution improves to 0.56 mm (FWHM). The DOI
      resolution is the layer thickness of 3.0 mm. We also find that optical-coupling
      media and SiPM-window materials have an impact on spatial resolution. The timing
      simulation with LYSO crystal yields a coincidence resolving time (CRT) of 200-400
      ps, which is slightly position dependent. And the introduction of optical
      barriers has minimum influence. The prototype CsI(Tl) detector, with a smaller
      area and fewer SiPMs, was measured to have central-area spatial resolutions of
      0.70 and 0.39 mm without and with optical barriers, respectively. These results
      match well with our simulations. An energy resolution of 6.4% was achieved at 662
      keV. CONCLUSION: A detector design based on a stack of monolithic scintillator
      layers that uses edge readouts offers several advantages over current block
      detectors for PET. For example, there is no tradeoff between spatial resolution
      and detection sensitivity since no reflector material displaces scintillator
      crystal, and submillimeter resolution can be achieved. DOI information is readily
      available, and excellent timing and energy resolutions are possible.

PMID- 29635735
TI  - Descriptive profile of the academic integrity of Australian occupational therapy
      students.
AB  - BACKGROUND: Academic integrity is the moral code of academia. Students who
      demonstrate trustworthiness in an academic setting are more likely to be
      dependable in a clinical setting. It is, therefore, important for occupational
      therapy academic and fieldwork educators to know the academic integrity profile
      of their students and to address any areas of academic dishonesty in curriculum
      design and delivery. To date, there has been no baseline description of the
      academic honesty profile of Australian occupational therapy students. AIM: To
      establish a baseline of academic integrity and academic dishonesty among
      occupational therapy undergraduate and graduate-entry masters students in a
      cohort of Australian students. METHODS: Seven hundred and one students from five
      Australian universities completed a self-report questionnaire comprising
      demographic questions and six standardised scales measuring academic integrity.
      RESULTS: Overall, occupational therapy students reported high levels of academic
      and fieldwork integrity; however, some areas of concerns exist. Students report
      copying material without citations at least once during their studies (55%),
      obtaining test questions at least once during their studies (42.6%) or padding
      out a bibliography (39.5%). CONCLUSION: Occupational therapy education needs to
      continue to emphasise the importance of academic and fieldwork integrity.
      Students need to be explicitly taught what academic honesty and dishonesty is and
      be provided with the resources and time to complete academic work to reduce the
      risk of academic dishonesty.

PMID- 29635736
TI  - Comments on Effect of Gabapentin on Delayed Discharge from the Postanesthesia
      Care Unit.

PMID- 29635738
TI  - Genealogy as a Counter-Human Science.

PMID- 29635737
TI  - Evolutionary history of HOMEODOMAIN LEUCINE ZIPPER transcription factors during
      plant transition to land.
AB  - Plant transition to land required several regulatory adaptations. The mechanisms
      behind these changes remain unknown. Since the evolution of transcription factors
      (TFs) families accompanied this transition, we studied the HOMEODOMAIN LEUCINE
      ZIPPER (HDZ) TF family known to control key developmental and environmental
      responses. We performed a phylogenetic and bioinformatics analysis of HDZ genes
      using transcriptomic and genomic datasets from a wide range of Viridiplantae
      species. We found evidence for the existence of HDZ genes in chlorophytes and
      early-divergent charophytes identifying several HDZ members belonging to the four
      known classes (I-IV). Furthermore, we inferred a progressive incorporation of
      auxiliary motifs. Interestingly, most of the structural features were already
      present in ancient lineages. Our phylogenetic analysis inferred that the origin
      of classes I, III, and IV is monophyletic in land plants in respect to
      charophytes. However, class IIHDZ genes have two conserved lineages in
      charophytes and mosses that differ in the CPSCE motif. Our results indicate that
      the HDZ family was already present in green algae. Later, the HDZ family expanded
      accompanying critical plant traits. Once on land, the HDZ family experienced
      multiple duplication events that promoted fundamental neo- and
      subfunctionalizations for terrestrial life.

PMID- 29635740
TI  - Why do children read more? The influence of reading ability on voluntary reading
      practices.
AB  - BACKGROUND: This study investigates the causal relationships between reading and
      print exposure and investigates whether the amount children read outside school
      determines how well they read, or vice versa. Previous findings from behavioural
      studies suggest that reading predicts print exposure. Here, we use twin-data and
      apply the behaviour-genetic approach of direction of causality modelling,
      suggested by Heath et al. (), to investigate the causal relationships between
      these two traits. METHOD: Partial data were available for a large sample of twin
      children (N = 11,559) and 262 siblings, all enrolled in the Netherlands Twin
      Register. Children were assessed around 7.5 years of age. Mothers completed
      questionnaires reporting children's time spent on reading activities and reading
      ability. Additional information on reading ability was available through teacher
      ratings and performance on national reading tests. For siblings reading test,
      results were available. RESULTS: The reading ability of the twins was comparable
      to that of the siblings and national norms, showing that twin findings can be
      generalized to the population. A measurement model was specified with two latent
      variables, Reading Ability and Print Exposure, which correlated .41. Heritability
      analyses showed that Reading Ability was highly heritable, while genetic and
      environmental influences were equally important for Print Exposure. We exploited
      the fact that the two constructs differ in genetic architecture and fitted
      direction of causality models. The results supported a causal relationship
      running from Reading Ability to Print Exposure. CONCLUSIONS: How much and how
      well children read are moderately correlated. Individual differences in print
      exposure are less heritable than individual differences in reading ability.
      Importantly, the present results suggest that it is the children's reading
      ability that determines how much they choose to read, rather than vice versa.

PMID- 29635739
TI  - Smart-Dust-Nanorice for Enhancement of Endogenous Raman Signal, Contrast in
      Photoacoustic Imaging, and T2-Shortening in Magnetic Resonance Imaging.
AB  - Raman microspectroscopy provides chemo-selective image contrast, sub-micrometer
      resolution, and multiplexing capabilities. However, it suffers from weak signals
      resulting in image-acquisition times of up to several hours. Surface-enhanced
      Raman scattering (SERS) can dramatically enhance signals of molecules in close
      vicinity of metallic surfaces and overcome this limitation. Multimodal, SERS
      active nanoparticles are usually labeled with Raman marker molecules, limiting
      SERS to the coating material. In order to realize multimodal imaging while
      acquiring the rich endogenous vibronic information of the specimen, a core-shell
      particle based on "Nanorice", where a spindle-shaped iron oxide core is
      encapsulated by a closed gold shell, is developed. An ultrathin layer of silica
      prevents agglomeration and unwanted chemical interaction with the specimen. This
      approach provides Raman signal enhancement due to plasmon resonance effects of
      the shell while the optical absorption in the near-infrared spectral region
      provides contrast in photoacoustic tomography. Finally, T2-relaxation of a
      magnetic resonance imaging (MRI) experiment is altered by taking advantage of the
      iron oxide core. The feasibility for Raman imaging is evaluated by nearfield
      simulations and experimental studies on the primate cell line COS1. MRI and
      photoacoustics are demonstrated in agarose phantoms illustrating the promising
      translational nature of this strategy for clinical applications in radiology.

PMID- 29635741
TI  - In vivo photoacoustic/ultrasonic dual-modality endoscopy with a miniaturized full
      field-of-view catheter.
AB  - Endoscopy is an essential clinical tool for the diagnosis of gastrointestinal
      (GI) tract cancer. A photoacoustic system that elegantly combines optical and
      ultrasound endoscopy advantages by providing high-sensitivity functional
      information and large imaging depth is a potentially powerful tool for GI tract
      imaging. Recently, several photoacoustic endoscopic imaging systems have been
      proposed and developed. However, the relatively large size and rigid length of
      the catheter make it difficult to translate them into wide clinical applications;
      while the existing system of a relatively small catheter, capable of in vivo
      animal imaging, is unable to acquire full (360 degrees ) field-of-view cross
      section images. In this study, we developed a photoacoustic/ultrasonic dual
      modality endoscopic system and a corresponding miniaturized, encapsulated imaging
      catheter, which provides a full 360 degrees  field-of-view. The diameter of the
      catheter is 2.5 mm, which is compatible with the 2.8-mm instrumental channel of a
      conventional clinical optical endoscope. Using this system, we demonstrate in
      vivo 3-dimensional endoscopic photoacoustic/ultrasonic imaging of the colorectum
      of a healthy Sprague Dawley rat, by depicting vasculature and morphology of the
      GI tract. The significantly improved imaging field of view, reduced catheter
      size, high-quality imaging results suggest that the developed
      photoacoustic/ultrasonic dual-modality endoscopy has a great potential to be
      translated into a broad range of clinical applications in gastroenterology.

PMID- 29635742
TI  - Morphosyntactic abilities of toddlers with hearing impairment and normal hearing:
      evidence from a sentence-repetition task.
AB  - BACKGROUND: While considerable research exists on morphosyntax of school-age
      children with hearing impairment (HI), little is known about development of
      morphosyntax at younger ages. Some studies show that young children with HI have
      a delay in language abilities compared with children with normal hearing (NH);
      conversely, other studies show evidence that they achieve age-appropriate
      language development. AIMS: To investigate whether characteristics of
      morphosyntactic development displayed by young children with HI are unique or
      whether they are similar to those of NH children. METHODS & PROCEDURES: Fifty
      four Hebrew-speaking children (15 with HI and 39 with NH), aged 22-40 months,
      completed a novel Hebrew sentence repetition (SRep) task designed to evaluate
      morphosyntactic abilities. Accuracy on the total correct structure, repetition of
      content and function words, and repetition of specific morphemes were compared
      across groups. OUTCOMES & RESULTS: At the earliest stages of combining words to
      sentences, toddlers in both groups showed a large variation in morphosyntactic
      development, with no significant difference between the two groups. Children with
      HI and NH showed similar results for the acquisition of morphemes and various
      syntactic structures. In the group of children with HI, hearing capability
      accounted for 28% of the variance of the SRep task. CONCLUSIONS & IMPLICATIONS:
      The findings suggest typical morphosyntax capacity at the onset of language
      development among of children with HI who are diagnosed early and receive
      intensive intervention.

PMID- 29635744
TI  - Regulated Expression of sgRNAs Tunes CRISPRi in E. coli.
AB  - Methods for implementing dynamically-controlled multi-gene programs could expand
      capabilities to engineer metabolism for efficiently producing high-value
      compounds. This work explores whether CRISPRi repression can be tuned in E. coli
      through the regulated expression of the CRISPRi machinery. When dCas9 is not
      limiting, variations in sgRNA expression alone can lead to CRISPRi repression
      levels ranging from 5- to 300-fold. Titrating sgRNA expression over a 2.5-fold
      range results in 16-fold changes in reporter gene expression. Many different
      classes of genetic controllers can generate 2.5-fold differences in
      transcription, suggesting they may be integrated into dynamically-regulated
      CRISPRi circuits. Finally, CRISPRi cannot be reversed for up to 12 hours by
      expressing a competing sgRNA later in the growth phase, indicating that CRISPR
      Cas:DNA interactions can be persistent in vivo. Collectively, these results
      identify genetic architectures for tuning CRISPRi repression through regulated
      sgRNA expression and suggest that dynamically-regulated CRISPRi systems targeting
      multiple genes may be within reach.

PMID- 29635743
TI  - In vitro assessment of quality of citrate-phosphate-dextrose-adenine-1 preserved
      feline blood collected by a commercial closed system.
AB  - BACKGROUND: Optimal procedure for storage of feline blood is needed. Open
      collection systems have been employed in feline medicine, thus limiting the
      possibility for storage. OBJECTIVES: To evaluate indicators of quality of feline
      blood stored for 35 days at +4 degrees C in a closed-collection system
      specifically designed for cats. ANIMALS: Eight healthy adult European domestic
      shorthair cats with a weight of 5-6.8 kg. METHODS: This is a case series study. A
      bacteriological test, CBC, blood smear, pH, osmotic fragility, 2,3
      diphosphoglycerate (2,3-DPG), and adenosine triphosphate (ATP) measurement were
      performed weekly on whole blood (WB) units from day 1 to day 35 after donation.
      The hemolysis index, lactate and potassium concentrations, prothrombin time (PT),
      activated partial thromboplastin time (aPTT), and fibrinogen were measured on
      plasma aliquots. RESULTS: One out of eight blood units (BUs) had bacterial growth
      (Serratia marcescens) at day 35. No significant differences were found regarding
      CBC, morphology, pH, and osmotic fragility. Despite high inter-individual
      variability and low starting levels, significant decreases in the mean
      concentrations of 2,3-DPG (T0 1.99 mmol/g Hb, SD 0.52, T35 1.25 mmol/g Hb, SD
      1.43; P = .003) and ATP (T0 1.45 mmol/g Hb, SD 0.71, T35 0.62 mmol/g Hb, SD 0.51;
      P < .001) were detected during the study, as opposed to an increase in hemolysis
      (T0 0.11 mmol/L, SD 0.07, T35 0.84 mmol/L, SD 0.19; P < .001), lactate (T0 3.30
      mmol/L, SD 0.86, T35 13.36 mmol/L, SD 2.90; P < .001), and potassium (T0 3.10
      mmol/L, SD 0.21, T35 4.12 mmol/L, SD 0.35; P < .001) concentrations. CONCLUSIONS
      AND CLINICAL IMPORTANCE: The commercial BU kit is appropriate for blood
      collection and conservation of WB in cats. The maintenance of WB quality
      indicators during storage is essential for future improvements of feline
      transfusion medicine.

PMID- 29635746
TI  - Isolation of pulmonary veins using a thermoreactive implantable device with
      external energy transfer: Evaluation in a porcine model.
AB  - BACKGROUND: Pulmonary vein isolation (PVI) is a well-established method for the
      treatment of symptomatic paroxysmal atrial fibrillation, but is only partly
      successful with a high rate of electrical reconnection. We introduce a novel
      technique in which PVI is accomplished by noninvasive heating of a dedicated
      thermoresponse implant inserted into the pulmonary veins (PV), demonstrated in a
      porcine model. METHODS: A self-expanding nitinol-based implant was positioned in
      the common inferior PV of 11 pigs, using a fluoroscopy-guided transatrial
      appendage approach. Ablation was performed through contactless energy transfer
      from a primary extracorporal coil to a secondary heat ring (HR) embedded in the
      proximal part of the implant. Electrophysiological conduction was assessed prior
      to and postablation, and at 3 months. Histological samples were obtained acutely
      (n  =  4) and after 3 months (n  =  7). RESULTS: In total, 13 PV implants were
      successfully positioned in the inferior PVs of 11 animals. Ablation was performed
      without injury of adjacent structures. PVI and bidirectional block was
      electrophysiologically confirmed in all cases immediately at the time of
      implantation and 3 months later in seven chronic animals in whom testing was
      repeated. Marked evidence of ablation around the proximal HR was evident at 3
      months postprocedure, with scar tissue formation and only mild neointimal
      proliferation. CONCLUSIONS: Successful PVI can be obtained by external
      electromagnetic heat transfer to a novel pulmonary vein implant.

PMID- 29635747
TI  - "... Casting Our Lot with Some Ways of Life and Not Others": Epistemic
      Reflexivity, Diffraction, Epistemic Responsibilities.

PMID- 29635745
TI  - The design and rationale of SAVE BC: The Study to Avoid CardioVascular Events in
      British Columbia.
AB  - Atherosclerotic cardiovascular disease (ASCVD) is highly heritable, particularly
      when it occurs at a young age. The screening of individuals with premature ASCVD,
      although often recommended, is not routinely performed. Strategies to address
      this gap in care are essential. We designed the Study to Avoid CardioVascular
      Events in British Columbia (SAVE BC) as a prospective, observational study of
      individuals with a new diagnosis of very premature ASCVD (defined as age <= 50
      years in males and age <= 55 years in females) and their first-degree relatives
      (FDRs) and spouses. FDRs and spouses will undergo screening for cardiovascular
      (CV) risk factors and subclinical ASCVD using a structured screening algorithm.
      All subjects will be followed longitudinally for >=10 years. The overall goal of
      SAVE BC is to evaluate the yield of a structured screening program for
      identifying individuals at risk of premature ASCVD. The primary objectives of
      SAVE BC are to identify and follow index cases with very premature ASCVD and
      their FDRs and to determine the diagnostic yield of a structured screening
      program for these individuals. We will collect data on CV risk factors,
      medication use, CV events, and healthcare costs in these individuals. SAVE BC
      will provide insight regarding approaches to identify individuals at risk for
      premature ASCVD with implications for prevention and treatment in this
      population.

PMID- 29635748
TI  - Neural correlates of enhanced executive functions: is less more?
AB  - Musical training has been associated with superior performance in various
      executive function tasks. To date, only a few neuroimaging studies have
      investigated the neural substrates of the supposed "musician advantage" in
      executive functions, precluding definite conclusions about its neural basis.
      Here, we provide a selective review of neuroimaging studies on plasticity and
      typical maturation of executive functions, with the aim of investigating how
      proficient performance in executive function tasks is reflected in brain
      activity. Specifically, we examine the evidence for the hypothesis that enhanced
      or mature executive functions are manifested as efficient use of neural systems
      supporting those functions. We also present preliminary results from a functional
      magnetic resonance imaging study suggesting-in line with this hypothesis-that
      musically trained adolescents recruit frontoparietal regions less strongly during
      executive functions tasks than untrained peers.

PMID- 29635749
TI  - Use of cosmetic products for treating certain diseases-Know the science.
AB  - BACKGROUND: Psoriasis being an incurable disease, the drug dependency of the
      patient in most occasions causes greater health problem than psoriasis. Wherever
      there is flare-up, immunosuppressive drugs and other antimitotic medicaments are
      necessary. Therefore, a safe cosmetic preparation with drug-like effect on
      certain triggering factors of psoriasis may revolutionize the treatment.
      OBJECTIVES: Objectives of this study were to determine the effect of the
      developed formulation on several key enzymes such as lipoxygenase, collagenase,
      elastase, and nullifying the free radicals and glycation. All these enzymes have
      cascading effect in triggering the problem to inflammatory level. METHODS:
      Biochemical and enzymatic assay was performed to determine the effect of the
      cosmetic formulation and its effective dosage. RESULT: The findings clearly show
      that the formulation is effective against all the key triggering factors of
      psoriasis. CONCLUSION: Findings undoubtedly establish the drug-like effect of
      nondrug formulation (cosmetic formulation). The use of this formulation may
      minimize the relative dependency of many steroids and other medicament. As the
      formulation contains only proven cosmetic ingredients and herbs, long-term use is
      unlikely to produce any side effects.

PMID- 29635750
TI  - High Intracellular Seed Train BiP Levels Correlate With Poor Production Culture
      Performance in CHO Cells.
AB  - Consistent cell culture performance is a prerequisite to ensure product quality
      consistency and achieve productivity goals for the manufacture of recombinant
      protein therapeutics, including monoclonal antibodies. Here a peculiar
      observation is reported where high levels of intracellular BiP in seed train
      cultures are consistently predictive of poor cell culture performance in the
      subsequent inoculum and production cultures for a monoclonal antibody produced in
      CHO cells. This investigation suggests that in this cell line the high
      intracellular BiP levels in the seed train are triggered by a slightly lower
      culture pH, which interferes with proper antibody folding and secretion. While
      the seed train culture does not display any obvious signs of the problem at
      slightly lower culture pH, inoculum trains, and production cultures sourced from
      these low pH seed trains display significantly lower cell growth and cell size.
      High intracellular BiP levels may interfere with UPR signaling, thereby hampering
      a proper and timely UPR response in the production media. Studies of other
      problematic cell lines have shown a similar correlation between intracellular BiP
      accumulation and poor production performance. The authors believe intracellular
      BiP levels in seed train should hence be low in order to increase the success
      rate in production.

PMID- 29635751
TI  - Quercetin reversed MDR in breast cancer cells through down-regulating P-gp
      expression and eliminating cancer stem cells mediated by YB-1 nuclear
      translocation.
AB  - Overexpression of P-glycoprotein (P-gp) plays an important role in mediating
      multidrug resistance (MDR), resulting in chemotherapy failure of tumor patients
      and enhancement of cancer stem cell characteristics. By preparing doxorubicin
      (Dox) resistant human breast cancer MCF-7 cells, here, we wanted to evaluate the
      effects of quercetin (Que) on MDR reversal activity and investigate its possible
      mechanism. MCF-7 and MCF-7/dox cells were respectively treated by Dox, paclitaxel
      (Pac), or vincristine (Vcr) with or without Que intervention for 24 hr. Cell
      viability, cell apoptosis, cell cycle, intracellular drug accumulation, the
      expression of P-gp and Y-box binding protein 1 (YB-1), and breast cancer stem
      cells (BCSCs) were then assessed. The results showed that Que significantly
      enhanced the antitumor activities of Dox, Pac, and Vcr in breast cancer cells. In
      addition, combined treatment of Dox, Pac, or Vcr with Que significantly
      downregulated P-gp expression and eliminated BCSCs. Furthermore, combined
      treatment of Dox, Pac, or Vcr with Que significantly inhibited nuclear
      translocation of YB-1. Thus, we speculated that Que reversed MDR in breast cancer
      cells through downregulating P-gp expression and eliminating cancer stem cells
      mediated by YB-1 nuclear translocation.

PMID- 29635753
TI  - Differences in physiological and biochemical characteristics in response to
      single and combined drought and salinity stresses between wheat genotypes
      differing in salt tolerance.
AB  - The combined drought and salinity stresses pose a serious challenge for crop
      production, but the physiological mechanisms behind the stresses responses in
      wheat remains poorly understood. Greenhouse pot experiment was performed to study
      differences in genotype response to the single and combined (D + S) stresses of
      drought (4% soil moisture, D) and salinity (100 mM NaCl, S) using two wheat
      genotypes: Jimai22 (salt tolerant) and Yangmai20 (salt-sensitive). Results showed
      that salinity, drought and/or D + S severely reduces plant growth, biomass and
      net photosynthetic rate, with a greater effect observed in Yangmai20 than
      Jimai22. A notable improvement in water use efficiency (WUE) by 239, 77 and 103%
      under drought, salinity and D + S, respectively, was observed in Jimai22.
      Moreover, Jimai22 recorded higher root K+ concentration in drought and salinity
      stressed condition and shoot K+ under salinity alone than that of Yangmai20.
      Jimai22 showed lower increase in malondialdehyde (MDA) accumulation, but higher
      activities of superoxide dismutase (SOD, EC 1.15.1.1) and guaicol peroxidase
      (POD, EC 1.11.1.7), under single and combined stresses, and catalase (CAT, EC
      1.11.1.6) and ascorbate peroxidase (APX, EC 1.11.1.11) under single stress. Our
      results suggest that high tolerance of Jimai22 in both drought and D + S stresses
      is closely associated with larger root length, higher Fv/Fm and less MDA contents
      and improved capacity of SOD and POD. Moreover, under drought Jimai22 tolerance
      is firmly related to higher root K+ concentration level and low level of Na+ ,
      high-net photosynthetic rate and WUE as well as increased CAT and APX activities
      to scavenge reactive oxygen species.

PMID- 29635752
TI  - Inhibition of carbonic anhydrase IX targets primary tumors, metastases, and
      cancer stem cells: Three for the price of one.
AB  - Human carbonic anhydrase (CA) IX is a tumor-associated protein, since it is
      scarcely present in normal tissues, but highly overexpressed in a large number of
      solid tumors, where it actively contributes to survival and metastatic spread of
      tumor cells. Due to these features, the characterization of its biochemical,
      structural, and functional features for drug design purposes has been extensively
      carried out, with consequent development of several highly selective small
      molecule inhibitors and monoclonal antibodies to be used for different purposes.
      Aim of this review is to provide a comprehensive state-of-the-art of studies
      performed on this enzyme, regarding structural, functional, and biomedical
      aspects, as well as the development of molecules with diagnostic and therapeutic
      applications for cancer treatment. A brief description of additional
      pharmacologic applications for CA IX inhibition in other diseases, such as
      arthritis and ischemia, is also provided.

PMID- 29635754
TI  - The effect of iron chelation therapy on overall survival in sickle cell disease
      and beta-thalassemia: A systematic review.
AB  - Red blood cell transfusions have become standard of care for the prevention of
      life-threatening anemia in patients with beta-thalassemia and sickle cell disease
      (SCD). However, frequent transfusions can lead to accumulation of iron that can
      result in liver cirrhosis, diabetes mellitus, arthritis, arrhythmias,
      cardiomyopathy, heart failure, and hypogonadotropic hypogonadism. Iron chelation
      therapy has been shown to reduce serum ferritin levels and liver iron content,
      but limitations of trial design have prevented any demonstration of improved
      survival. The objective of this systematic review was to investigate the impact
      of iron chelation therapy on overall and event-free survival in patients with
      beta-thalassemia and SCD. Eighteen articles discussing survival in beta
      thalassemia and 3 in SCD were identified. Overall iron chelation therapy resulted
      in better overall survival, especially if it is instituted early and compliance
      is maintained. Comparative studies did not show any significant differences
      between available iron chelation agents, although there is evidence that
      deferiprone is better tolerated than deferoxamine and that compliance is more
      readily maintained with the newer oral drugs, deferiprone and deferasirox. Iron
      chelation therapy, particularly the second-generation oral agents, appears to be
      associated with improved overall and event-free survival in transfusion-dependent
      patients with beta-thalassemia and patients with SCD.

PMID- 29635755
TI  - Exact and exclusive electron localization indices within QTAIM atomic basins.
AB  - Novel measures of electron (de)localization within the Quantum Theory of Atoms in
      Molecules (QTAIM) atomic basins are presented which, unlike orthodox localization
      indices (LIs), are fully exclusive and can be easily visualized. This work shows
      that QTAIM-defined LIs describe a portion of interatomic delocalized electrons;
      hence, the chemical/physical interpretation of orthodox LIs is misleading. Using
      the recently introduced Fragment, Atomic, Localized, Delocalized, and Interatomic
      (FALDI) density decomposition technique we derive two novel sets of LIs and
      delocalization indices (DIs), by accounting for the overlap between localized and
      delocalized density functions. The FALDI-based LIs and DIs perfectly recover
      chemically expected core and bonded electron count. Usefulness of new
      (de)localization indices and their 3D representations were demonstrated on a
      number of examples, including formamide and benzene. We therefore expect that the
      scheme reported in this work will provide a valuable stepping stone between
      classical conceptual chemistry and quantum chemical topology. (c) 2018 Wiley
      Periodicals, Inc.

PMID- 29635756
TI  - 3D Aerogel of Graphitic Carbon Nitride Modified with Perylene Imide and Graphene
      Oxide for Highly Efficient Nitric Oxide Removal under Visible Light.
AB  - 3D materials are considered promising for photocatalytic applications in air
      purification because of their large surface areas, controllability, and
      recyclability. Here, a series of aerogels consisting of graphitic-carbon nitride
      (g-C3 N4 ) modified with a perylene imide (PI) and graphene oxide (GO) are
      prepared for nitric oxide (NO) removal under visible-light irradiation. All of
      the photocatalysts exhibit excellent activity in NO removal because of the strong
      light absorption and good planarity of PI-g-C3 N4 coupled with the favorable
      charge transport properties of GO, which slow the recombination of electron-hole
      pairs. The aerogel containing thiophene displays the most efficient NO removal of
      the aerogel series, with a removal ratio of up to 66%. Density functional theory
      calculations are conducted to explain this result and recycling experiments are
      carried out to verify the stability and recyclability of these photocatalysts.

PMID- 29635757
TI  - Oesophageal causes of dysphagia localised only to the pharynx: Implications for
      the suspected head and neck cancer pathway.
AB  - OBJECTIVES: Dysphagia is a presenting symptom of both pharyngeal and oesophageal
      cancers. The referral pathway choice is determined by whether it is thought to be
      oropharyngeal or oesophageal, and this is in turn influenced by whether dysphagia
      is perceived to be above or below the suprasternal notch. We studied the
      concordance between the presence of pharynx-localised dysphagia (PLD) and the
      location of the underlying disease processes. DESIGN: A subset analysis of the
      Dysphagia Hotline Cohort, collected between 2004 and 2015, of patients with PLD
      and a structural diagnosis. MAIN OUTCOME MEASURES: Information about patient
      demography and presenting symptoms were recorded. The incisor-to-pathology
      distance, and the nature of the pathology, were recorded. Logistic regression
      analysis was used to identify independent predictors of malignancy. RESULTS: The
      study included 177 patients. There were 92 males, and mean age at presentation
      was 74 years. The commonest benign pathologies were cricopharyngeal dysfunction
      with or without pharyngeal pouch (n = 67), peptic stricture (n = 44) and
      Schatzki's ring (n = 11). There were 49 cases of cancer, including one
      hypopharyngeal cancer, one cervical oesophageal cancer, 28 cancers of the
      upper/mid-thoracic oesophagus, 15 cancers of the lower thoracic oesophagus and 4
      cardio-oesophageal cancers. In 105 (59%) patients, PLD was caused by oesophageal
      disease. Independent predictors of malignancy were weight-change (loss >2.7 kg),
      a short history (<12 weeks) and presence of odynophagia. Nineteen (39%) of
      oesophageal cancers that presented with dysphagia that was localised only to the
      pharynx would have been beyond the reach of rigid oesophagoscopy. CONCLUSIONS:
      Pharynx-localised dysphagia is more likely to be a referred symptom of structural
      oesophageal disease, including cancer, than a primary symptom of structural
      pharyngeal disease. Absence of additional alarm symptoms such as a short history,
      weight-loss, and odynophagia, do not adequately exclude the possibility of
      oesophageal cancer. When the differential diagnosis of PLD includes malignancy,
      cancer should be presumed to be arising from the oesophagus or the cardio
      oesophageal region until proven otherwise. This requires direct visualisation of
      the mucosal surfaces of the oesophagus and the cardio-oesophageal region, using
      either transoral or transnasal flexible endoscopy, irrespective of whether the
      initial assessment occurs within head and neck or upper gastrointestinal
      suspected cancer pathways.

PMID- 29635758
TI  - Hyperpolarization-activated channels shape temporal patterns of ectopic
      spontaneous discharge in C-nociceptors after peripheral nerve injury.
AB  - BACKGROUND: Neuropathic pain is thought to be mediated by aberrant impulses from
      sensitized primary afferents, and the temporal summation of the discharges might
      also influence nociceptive processing. Hyperpolarization-activated cyclic
      nucleotide-gated (HCN) channels (Ih current) generate rhythmic activity in
      neurons within the central nervous system and contribute to nociceptors
      excitability in neuropathic pain. METHODS: We searched for single fibres with
      ectopic spontaneous discharges from an in vitro preparation in mice containing a
      neuroma formed in a peripheral branch of the saphenous nerve together with the
      undamaged branches. RESULTS: Both damaged (axotomized) and undamaged fibres
      (putative intact) developed ectopic spontaneous activity with different temporal
      spike trains: Clock-like, Irregular or Bursts. The Ih current blocker, ZD7288,
      significantly suppressed ectopic spontaneous discharges in nociceptive fibres
      (3/5 Adelta- and 24/31 C-units and 1 nonclassified) by 64%. Additionally, ZD7288
      changed the spike patterns of 5/7 Clock-like and 3/4 Burst units to Irregular.
      Exogenous cAMP produced a significant ~65% increase in the ectopic firing in 5
      Irregular fibres, which was restored by ZD7288. In six additional fibres (three
      Clock-like and three Irregular), exogenous cAMP had no further effect, but co
      application with ZD7288 decreased their discharge by half. These units showed
      significant higher levels of discharges than the cAMP-sensitive ones.
      CONCLUSIONS: Our data suggest that HCN channels modulate ectopic spontaneous
      firing in C-nociceptors and shape their temporal patterns of discharge which
      will, ultimately, modify the nociceptive message received and processed by second
      order neurons. SIGNIFICANCE: We show an involvement of HCN channels in the
      modulation of ectopic spontaneous discharges from C-nociceptors. This finding
      exposes a mechanism of nociceptive transmission enhancement and highlights the
      clinical relevance of peripheral HCN blockade for spontaneous pain relief during
      neuropathy.

PMID- 29635759
TI  - Response to adenosine during narrow QRS tachycardia and sinus rhythm: What is the
      mechanism?

PMID- 29635760
TI  - What are the additional signs and symptoms in patients with detrusor
      underactivity and coexisting detrusor overactivity?
AB  - AIMS: This study aimed to determine what difference the inclusion of patients
      with coexisting detrusor overactivity (DO) makes to the signs and symptoms of
      patients with detrusor underactivity (DU). METHODS: A total of 250 male and 435
      female urodynamic tests were analyzed retrospectively. Signs and symptoms which
      showed a statistically significant difference between DU without DO and DU with
      DO were identified. RESULTS: Males with DO in addition to DU had higher age and
      number of daily micturitions, and were more likely to report urgency with or
      without urgency incontinence than males with DU without DO. They also had lower
      volumes for first desire to void, volume voided, and post void residual urine,
      lower abdominal pressure at Qmax and were less likely to report a history of
      retention or reduced bladder filling sensation than males with DU without DO.
      Females with DO in addition to DU had higher age and BMI, and were more likely to
      report urgency incontinence, higher day and night pad usage, constipation and
      have reduced anal tone than females with DU without DO. They also had lower
      volumes for first desire to void, volume voided, and post void residual urine,
      and lower abdominal pressure at Qmax than females who had DU without DO.
      CONCLUSIONS: There are differences in signs and symptoms between patients who
      have DU without DO, compared to patients having DU with DO. This understanding
      will help future studies investigating treatment options for DU patients.

PMID- 29635761
TI  - Water-Dispersible Polydopamine-Coated Nanofibers for Stimulation of Neuronal
      Growth and Adhesion.
AB  - Hybrid nanomaterials have shown great potential in regenerative medicine due to
      the unique opportunities to customize materials properties for effectively
      controlling cellular growth. The peptide nanofiber-mediated auto-oxidative
      polymerization of dopamine, resulting in stable aqueous dispersions of
      polydopamine-coated peptide hybrid nanofibers, is demonstrated. The catechol
      residues of the polydopamine coating on the hybrid nanofibers are accessible and
      provide a platform for introducing functionalities in a pH-responsive polymer
      analogous reaction, which is demonstrated using a boronic acid modified
      fluorophore. The resulting hybrid nanofibers exhibit attractive properties in
      their cellular interactions: they enhance neuronal cell adhesion, nerve fiber
      growth, and growth cone area, thus providing great potential in regenerative
      medicine. Furthermore, the facile modification by pH-responsive supramolecular
      polymer analog reactions allows tailoring the functional properties of the hybrid
      nanofibers in a reversible fashion.

PMID- 29635762
TI  - Principal component analysis-based imaging angle determination for 3D motion
      monitoring using single-slice on-board imaging.
AB  - PURPOSE: Through-plane motion introduces uncertainty in three-dimensional (3D)
      motion monitoring when using single-slice on-board imaging (OBI) modalities such
      as cine MRI. We propose a principal component analysis (PCA)-based framework to
      determine the optimal imaging plane to minimize the through-plane motion for
      single-slice imaging-based motion monitoring. METHODS: Four-dimensional computed
      tomography (4DCT) images of eight thoracic cancer patients were retrospectively
      analyzed. The target volumes were manually delineated at different respiratory
      phases of 4DCT. We performed automated image registration to establish the 4D
      respiratory target motion trajectories for all patients. PCA was conducted using
      the motion information to define the three principal components of the
      respiratory motion trajectories. Two imaging planes were determined perpendicular
      to the second and third principal component, respectively, to avoid imaging with
      the primary principal component of the through-plane motion. Single-slice images
      were reconstructed from 4DCT in the PCA-derived orthogonal imaging planes and
      were compared against the traditional AP/Lateral image pairs on through-plane
      motion, residual error in motion monitoring, absolute motion amplitude error and
      the similarity between target segmentations at different phases. We evaluated the
      significance of the proposed motion monitoring improvement using paired t test
      analysis. RESULTS: The PCA-determined imaging planes had overall less through
      plane motion compared against the AP/Lateral image pairs. For all patients, the
      average through-plane motion was 3.6 mm (range: 1.6-5.6 mm) for the AP view and
      1.7 mm (range: 0.6-2.7 mm) for the Lateral view. With PCA optimization, the
      average through-plane motion was 2.5 mm (range: 1.3-3.9 mm) and 0.6 mm (range:
      0.2-1.5 mm) for the two imaging planes, respectively. The absolute residual error
      of the reconstructed max-exhale-to-inhale motion averaged 0.7 mm (range: 0.4-1.3
      mm, 95% CI: 0.4-1.1 mm) using optimized imaging planes, averaged 0.5 mm (range:
      0.3-1.0 mm, 95% CI: 0.2-0.8 mm) using an imaging plane perpendicular to the
      minimal motion component only and averaged 1.3 mm (range: 0.4-2.8 mm, 95% CI: 0.4
      2.3 mm) in AP/Lateral orthogonal image pairs. The root-mean-square error of
      reconstructed displacement was 0.8 mm for optimized imaging planes, 0.6 mm for
      imaging plane perpendicular to the minimal motion component only, and 1.6 mm for
      AP/Lateral orthogonal image pairs. When using the optimized imaging planes for
      motion monitoring, there was no significant absolute amplitude error of the
      reconstructed motion (P = 0.0988), while AP/Lateral images had significant error
      (P = 0.0097) with a paired t test. The average surface distance (ASD) between
      overlaid two-dimensional (2D) tumor segmentation at end-of-inhale and end-of
      exhale for all eight patients was 0.6 +/- 0.2 mm in optimized imaging planes and
      1.4 +/- 0.8 mm in AP/Lateral images. The Dice similarity coefficient (DSC)
      between overlaid 2D tumor segmentation at end-of-inhale and end-of-exhale for all
      eight patients was 0.96 +/- 0.03 in optimized imaging planes and 0.89 +/- 0.05 in
      AP/Lateral images. Both ASD (P = 0.034) and DSC (P = 0.022) were significantly
      improved in the optimized imaging planes. CONCLUSIONS: Motion monitoring using
      imaging planes determined by the proposed PCA-based framework had significantly
      improved performance. Single-slice image-based motion tracking can be used for
      clinical implementations such as MR image-guided radiation therapy (MR-IGRT).

PMID- 29635763
TI  - Association of support from family and friends with self-leadership for making
      long-term lifestyle changes in patients with colorectal cancer.
AB  - The purpose of this study was to examine the association of support from family
      and friends for adoption of healthy eating habits and performing exercise with
      improvements of self-leadership in patients with colorectal cancer (CRC). This
      cross-sectional study examined 251 patients with CRC who received primary
      curative surgery in South Korea. Demographic and clinical information, receipt of
      social support for adoption of healthy eating habits and performing exercise and
      self-leadership were collected. Greater participation by family and the use of
      rewards for performance of exercise were associated with greater behavioural
      awareness and volition, greater task motivation and constructive cognition of
      self-leadership in patients. Patients exercising with friends had greater task
      motivation in self-leadership. The use of rewards by family was associated with
      performing and maintaining exercise programme for more than 6 months, and family
      encouragement to adopt healthy eating habits was associated with excellent
      quality of diet. Family support for exercising and adopting healthy eating habits
      had more wide-ranging benefits in self-leadership than support from friends;
      however, support from each group improved self-leadership. Support from family
      was valuable for increasing the actual performance of exercise and for helping
      patients with cancer to adopt healthy diets.

PMID- 29635764
TI  - Postoperative pain management in children: Guidance from the pain committee of
      the European Society for Paediatric Anaesthesiology (ESPA Pain Management Ladder
      Initiative).
AB  - The main remit of the European Society for Paediatric Anaesthesiology (ESPA) Pain
      Committee is to improve the quality of pain management in children. The ESPA Pain
      Management Ladder is a clinical practice advisory based upon expert consensus to
      help to ensure a basic standard of perioperative pain management for all
      children. Further steps are suggested to improve pain management once a basic
      standard has been achieved. The guidance is grouped by the type of surgical
      procedure and layered to suggest basic, intermediate, and advanced pain
      management methods. The committee members are aware that there are marked
      differences in financial and personal resources in different institutions and
      countries and also considerable variations in the availability of analgesic drugs
      across Europe. We recommend that the guidance should be used as a framework to
      guide best practice.

PMID- 29635766
TI  - Complex Coacervate Core Micelles Containing Poly(vinyl alcohol) Inhibit Ice
      Recrystallization.
AB  - Complex coacervate core micelles (C3Ms) form upon complexation of oppositely
      charged copolymers. These co-assembled structures are widely investigated as
      promising building blocks for encapsulation, nanoparticle synthesis, multimodal
      imaging, and coating technology. Here, the impact on ice growth is investigated
      of C3Ms containing poly(vinyl alcohol), PVA, which is well known for its high ice
      recrystallization inhibition (IRI) activity. The PVA-based C3Ms are prepared upon
      co-assembly of poly(4-vinyl-N-methyl-pyridinium iodide) and poly(vinyl alcohol)
      block-poly(acrylic acid). Their formation conditions, size, and performance as
      ice recrystallization inhibitors are studied. It is found that the C3Ms exhibit
      IRI activity at PVA monomer concentrations as low as 1 * 10-3 m. The IRI efficacy
      of PVA-C3Ms is similar to that of linear PVA and PVA graft polymers, underlining
      the influence of vinyl alcohol monomer concentration rather than polymer
      architecture.

PMID- 29635765
TI  - Mice with reduced expression of the telomere-associated protein Ft1 develop p53
      sensitive progeroid traits.
AB  - Human AKTIP and mouse Ft1 are orthologous ubiquitin E2 variant proteins involved
      in telomere maintenance and DNA replication. AKTIP also interacts with A- and B
      type lamins. These features suggest that Ft1 may be implicated in aging
      regulatory pathways. Here, we show that cells derived from hypomorph Ft1 mutant
      (Ft1kof/kof ) mice exhibit telomeric defects and that Ft1kof/kof animals develop
      progeroid traits, including impaired growth, skeletal and skin defects, abnormal
      heart tissue, and sterility. We also demonstrate a genetic interaction between
      Ft1 and p53. The analysis of mice carrying mutations in both Ft1 and p53
      (Ft1kof/kof ; p53ko/ko and Ft1kof/kof ; p53+/ko ) showed that reduction in p53
      rescues the progeroid traits of Ft1 mutants, suggesting that they are at least in
      part caused by a p53-dependent DNA damage response. Conversely, Ft1 reduction
      alters lymphomagenesis in p53 mutant mice. These results identify Ft1 as a new
      player in the aging process and open the way to the analysis of its interactions
      with other progeria genes using the mouse model.

PMID- 29635767
TI  - Movement-based seizure detection.
AB  - This is a critical review and comment on the use of movement detection in
      epileptic seizures. The detection of rhythmic movement components, such as the
      clonic part of tonic-clonic seizures, is essential in all seizure detection based
      on movement sensors. Of the many available movement sensor types, accelerometric
      sensors are used most often. Eleven video-electroencephalographic (EEG) and 1
      field study have been carried out. The results of these clinical trials depend on
      the population, study design, and seizure evolution. In video-EEG monitoring
      units, sensitivity for tonic-clonic seizures varied from 31% to 95%, and positive
      predictive value from 4% to 60%. In a field trial in a residential adult
      population with intellectual disability, sensitivity was 14% and positive
      predictive value was 82%, whereas in patients admitted to an epilepsy clinic, a
      bed sensor had a sensitivity of 84% (no positive predictive value was given). The
      algorithms using the "rhythmic movement" component at the end of a tonic-clonic
      seizure are reliable (few false-positive alarms) but miss less typical seizure
      patterns that are mostly present in people with associated brain development
      disturbances. Other modalities (heart rate and electromyography) are needed to
      increase the detection performance. Advanced accelerometric techniques allow us
      to gain greater insight into seizure evolution patterns, possibilities for
      neuromodulation, and the influence of antiepileptic drugs on specific seizure
      components.

PMID- 29635768
TI  - Post-translational cleavage pattern of Lupinus angustifolius gamma-conglutin.
AB  - BACKGROUND: Protein post-translational modifications are a key element for the
      functional diversity of the proteome. The modifications generally refer to the
      addition of functional groups to certain proteins; however, proteolytic cleavage
      is also one of the relevant events during protein maturation. gamma-Conglutin is
      a unique protein fraction present in lupin seeds that is marked by numerous
      unusual properties. This protein fraction undergoes very complex post
      translational maturation. Unfortunately, the precise mechanism of gamma-conglutin
      post-translational processing is not yet fully understood. RESULTS: Two
      independent methods were used to study gamma-conglutin post-translational
      cleavage processing. Edman N-terminal sequencing indicates that the signal
      peptide is processed at Tyr34, while alpha- and beta-subunit cleavage takes place
      between Ser295 and Ser296. High-resolution mass spectrometry revealed a great
      diversity of N-terminal sequences of gamma-conglutin alpha-subunit. However, most
      abundant peptides also began from Tyr34. Mass spectrometric analyses additionally
      confirmed the subunit cleavage position between two serine residues. CONCLUSIONS:
      The results indicate that the proteolytic processing of gamma-conglutin signal
      peptide is not precise. On the other hand, the post-translational cleavage
      between alpha- and beta-subunits of gamma-conglutin is very conserved.
      Interestingly, the results also indicate that proteolytic processing leading to
      the formation of two subunits of gamma-conglutin is incomplete, leaving a certain
      amount of the protein in an uncut form. (c) 2018 Society of Chemical Industry.

PMID- 29635769
TI  - Degradation kinetics of aflatoxin B1 and B2 in solid medium by using pulsed light
      irradiation.
AB  - BACKGROUND: Pulsed light (PL) is a new potential technology to degrade aflatoxin.
      The objective of this study was to investigate the degradation characters of
      aflatoxin B1 (AFB1 ) and B2 (AFB2 ) treated under PL irradiation. A kinetic
      degradation study of AFB1 and AFB2 in solid medium was performed under PL
      irradiation at different initial concentrations of AFB1 (229.9, 30.7 and 17.8 MUg
      kg-1 ) and AFB2 (248.2, 32.2 and 19.5 MUg kg-1 ) and irradiation intensities
      (2.86, 1.60 and 0.93 W cm-2 ) of PL. A second-order reaction model was applied to
      describe degradation of AFB1 and AFB2 . RESULTS: The results showed that the
      degradation of AFB1 and AFB2 followed the second-order reaction kinetic model
      well (R2  > 0.97). The degradation rate was proportional to the intensities of PL
      irradiation and the initial concentrations of aflatoxins. CONCLUSION: It is
      concluded that the degradation of AFB1 and AFB2 with the use of PL could be
      accurately described using the second-order reaction kinetic model. (c) 2018
      Society of Chemical Industry.

PMID- 29635770
TI  - Chromhidrosis due to exogenous oxidizing heavy metals: Clinical and laboratory
      findings.
AB  - BACKGROUND/OBJECTIVES: Chromhidrosis is a rare condition of which there are only
      a few case reports in the literature. The aim of this study was to evaluate
      clinical, laboratory, and possible environmental factors in 13 patients with
      chromhidrosis to elucidate causative agents. METHODS: Data were obtained from the
      medical records of 13 patients with colored sweating between October 2015 and
      November 2016 (7 infants <1 year of age, 5 adults, 1 adolescent). RESULTS:
      Physical examination was normal in all patients. Nine of 12 had high calculated
      serum free copper (75%). Urine glutamine was measured in 13 patients and was high
      in 11 (84.6%). Ten patients drank natural mineral water from Uludag Mountain, and
      two were exposed to an intrauterine device containing copper. One patient (8%)
      was not exposed to Uludag Mountain natural water or an intrauterine device.
      CONCLUSION: We propose that chronic exposure to water or devices that contain
      high amounts of heavy metal and ammonium may contribute to CH.

PMID- 29635771
TI  - Diagnosing latent bipolar disorder: A clinical dilemma.

PMID- 29635772
TI  - Biogenic selenium nanoparticles synthesized by Stenotrophomonas maltophilia
      SeITE02 loose antibacterial and antibiofilm efficacy as a result of the
      progressive alteration of their organic coating layer.
AB  - Increasing emergence of drug-resistant microorganisms poses a great concern to
      clinicians; thus, new active products are urgently required to treat a number of
      infectious disease cases. Different metallic and metalloid nanoparticles have so
      far been reported as possessing antimicrobial properties and proposed as a
      possible alternative therapy against resistant pathogenic microorganisms. In this
      study, selenium nanoparticles (SeNPs) synthesized by the environmental bacterial
      isolate Stenotrophomonas maltophilia SeITE02 were shown to exert a clear
      antimicrobial and antibiofilm activity against different pathogenic bacteria,
      either reference strains or clinical isolates. Antimicrobial and antibiofilm
      capacity seems to be strictly linked to the organic cap surrounding biogenic
      nanoparticles, although the actual role played by this coating layer in the
      biocidal action remains still undefined. Nevertheless, evidence has been gained
      that the progressive loss in protein and carbohydrate content of the organic cap
      determines a decrease in nanoparticle stability. This leads to an alteration of
      size and electrical properties of SeNPs along with a gradual attenuation of their
      antibacterial efficacy. Denaturation of the coating layer was proved even to have
      a negative effect on the antibiofilm activity of these nanoparticles. The
      pronounced antimicrobial efficacy of biogenic SeNPs compared to the denatured
      ones can - in first instance - be associated with their smaller dimensions. This
      study showed that the native organic coating layer of biogenic SeNPs functions in
      avoiding aggregation and maintaining electrostatic stability of the
      nanoparticles, thus allowing them to maintain efficient antimicrobial and
      antibiofilm capabilities.

PMID- 29635773
TI  - Synthesis and Stereochemical Revision of the C31-C67 Fragment of Amphidinol 3.
AB  - Amphidinol 3 (AM3) is a marine natural product produced by the dinoflagellate
      Amphidinium klebsii. Although the absolute configuration of AM3 was determined in
      1999 by extensive NMR analysis and degradation of the natural product, it was a
      daunting task because of the presence of numerous stereogenic centers on the
      acyclic carbon chain and the limited availability from natural sources.
      Thereafter, revisions of the absolute configurations at C2 and C51 were reported
      in 2008 and 2013, respectively. Reported herein is the revised absolute
      configuration of AM3: 32S, 33R, 34S, 35S, 36S, and 38S based on the chemical
      synthesis of partial structures corresponding to the C31-C67 fragment of AM3 in
      combination with degradation of the natural product. The revised structure is
      unique in that both antipodal tetrahydropyran counterparts exist on a single
      carbon chain. The structural revision of AM3 may affect proposed structures of
      congeners related to the amphidinols.

PMID- 29635774
TI  - Fermented meat sausages from game and venison: what are the opportunities and
      limitations?
AB  - An increase in the acceptance, demand and production of game meat and venison has
      been experienced globally. Game meat and venison fit into consumers' ideology of
      healthy and environmentally friendly meat when compared to domesticated animals.
      Opportunities exist to explore the use of these meat sources in developing new
      products, particularly as game meat and venison in their fresh state are
      sometimes perceived as being tough. Consumers have shown a trend for trying
      exciting new products with different organoleptic qualities, and fermented
      sausages occupy a special niche in the gastro-economic trade. In this review, the
      production potential of game meat and venison and its prospective use in the
      development of fermented sausages are discussed. Emphasis is placed on the
      importance of meat characteristics in textural and sensorial development as well
      as the safety of fermented sausages. Additionally, consumers' perception of
      venison and game meat is discussed. Possible areas of research and knowledge gaps
      are highlighted, particularly the potential use of meat with high pH and
      microbial load. (c) 2018 Society of Chemical Industry.

PMID- 29635776
TI  - An automated intravaginal dynamometer: Reliability metrics and the impact of
      testing protocol on active and passive forces measured from the pelvic floor
      muscles.
AB  - AIMS: (1) To determine the reliability of an automated dynamometer designed to
      assess pelvic floor muscle (PFM) strength and resistance to passive elongation.
      (2) To evaluate the impact of PFM length and rate of tissue elongation on
      dynamometric outcomes. METHODS: At each of two sessions, twenty nulliparous women
      performed three maximum voluntary contractions (MVC) of their PFMs with the
      dynamometer set to two different anteroposterior (AP) diameters (25 mm, 35 mm).
      Next, with PFMs relaxed, the arms of the dynamometer opened three times to 40 mm
      at two speeds (25 mm/s, 50 mm/s). Outcomes included baseline force, peak force,
      relative peak force, rate of force development (RFD), stiffness and stress
      relaxation. Repeated-measures ANOVAs were used to test trial, day, and task
      effects (alpha = 0.05), and intra-class correlation coefficients (ICCs) were
      computed. RESULTS: Forces measured on MVC were higher with the larger AP
      diameter, and passive resistance was higher for the faster rate of tissue
      elongation. The between-trial reliability of all outcomes was excellent (0.82 <
      ICC < 0.98) for all measures except for peak force during the passive elongation
      task (0.56 < ICC < 0.93). Between-day reliability was good to excellent for
      active and passive RFD (0.75 < ICC < 0.93), stiffness (ICC = 0.77) and relative
      peak force (0.71 < ICC < 0.87); absolute force (0.11 < ICC < 0.85) and stress
      relaxation responses (0.19 < ICC < 0.98) tended to be less reliable. CONCLUSIONS:
      The reliability of the dynamometer is adequate for both clinical and research
      applications. Relative forces were more reliable than absolute forces. Dimensions
      and rate of tissue elongation should be controlled and reported with all pelvic
      floor muscle assessments as these parameters impact outcomes.

PMID- 29635775
TI  - Effects of renal impairment on transporter-mediated renal reabsorption of drugs
      and renal drug-drug interactions: A simulation-based study.
AB  - Renal impairment (RI) significantly impacts the clearance of drugs through
      changes in the glomerular filtration rate, protein binding and alterations in the
      expression of renal drug transport proteins and hepatic metabolizing enzymes. The
      objectives of this study were to evaluate quantitatively the effects of renal
      impairment on the pharmacokinetics of drugs undergoing renal transporter-mediated
      reabsorption. A previously published semi-mechanistic kidney model incorporating
      physiologically relevant fluid reabsorption and transporter-mediated active renal
      reabsorption (PMID: 26341876) was utilized in this study. The probe
      drug/transporter pair utilized was gamma-hydroxybutyric acid (GHB) and
      monocarboxylate transporter 1 (SCL16A1, MCT1). gamma-Hydroxybutyric acid
      concentrations in the blood and amount excreted into urine were simulated using
      ADAPT 5 for the i.v. dose range of 200-1500 mg/kg in rats and the impact of renal
      impairment on CLR and AUC was evaluated. A 90% decrease in GFR resulted in a >
      100-fold decrease in GHB CLR . When expression of reabsorptive transporters was
      decreased and fu was increased, CLR approached GFR. The effect of renal
      impairment on CLR was reduced when the expression of drug metabolizing enzymes
      (DME) was increased as a result of increased metabolic clearance; the converse
      held true when the DME expression was decreased. In conclusion, this study
      quantitatively demonstrated that the effects of renal insufficiency on the
      clearance of drugs is modulated by transporter expression, contribution of renal
      clearance to overall clearance, expression of drug metabolizing enzymes, fraction
      unbound and drug-drug interactions with inhibitors of renal transporters that may
      be increased in the presence of renal impairment.

PMID- 29635778
TI  - Corrigendum.

PMID- 29635777
TI  - Practical experiences of adopting assurance as a quantitative framework to
      support decision making in drug development.
AB  - All clinical trials are designed for success of their primary objectives. Hence,
      evaluating the probability of success (PoS) should be a key focus at the design
      stage both to support funding approval from sponsor governance boards and to
      inform trial design itself. Use of assurance-that is, expected success
      probability averaged over a prior probability distribution for the treatment
      effect-to quantify PoS of a planned study has grown across the industry in recent
      years, and has now become routine within the authors' company. In this paper, we
      illustrate some of the benefits of systematically adopting assurance as a
      quantitative framework to support decision making in drug development through
      several case-studies where evaluation of assurance has proved impactful in terms
      of trial design and in supporting governance-board reviews of project proposals.
      In addition, we describe specific features of how the assurance framework has
      been implemented within our company, highlighting the critical role that prior
      elicitation plays in this process, and illustrating how the overall assurance
      calculation may be decomposed into a sequence of conditional PoS estimates which
      can provide greater insight into how and when different development options are
      able to discharge risk.

PMID- 29635779
TI  - A retrospective clinico-pathological study comparing lichen planus pigmentosus
      with ashy dermatosis.
AB  - BACKGROUND/OBJECTIVES: Controversy persists as to whether lichen planus
      pigmentosus and ashy dermatosis are separate clinical entities. This study was
      conducted to examine the clinicopathological features and treatment outcome of
      the two conditions. METHODS: A retrospective medical chart review of all patients
      who were diagnosed with lichen planus pigmentosus or ashy dermatosis was
      conducted. The information collected included the participants' age at onset,
      site of onset, duration of disease, presence of precipitating factors,
      distribution of disease, pigmentation and presence of symptoms. In patients from
      whom a biopsy was taken the histopathological reports were included. RESULTS:
      Altogether 26 patients with ashy dermatosis and 29 with lichen planus pigmentosus
      were included in the study. Compared with ashy dermatosis, lichen planus
      pigmentosus had a more localised distribution with a preponderance for facial
      involvement, compared with the truncal preponderance in ashy dermatosis. Ashy
      dermatosis tended to have a more stable clinical course than lichen planus
      pigmentosus, which was more likely to wax and wane. The utility of histopathology
      in differentiating between the two conditions is low. CONCLUSION: Ashy dermatosis
      and lichen planus pigmentosus, as defined in this study, appear to be two
      separate clinical entities with distinguishable clinical features and natural
      histories.

PMID- 29635780
TI  - In vitro cytotoxicity of galvanically coupled magnesium-titanium particles on
      human osteosarcoma SAOS2 cells: A potential cancer therapy.
AB  - Osteosarcoma is a malignant bone cancer that occurs mostly in children and young
      adults. This study investigated the cytotoxicity of Mg and Mg-Ti microparticles
      to human osteosarcoma cells. Osteosarcoma cells were killed in a dosage-dependent
      manner when cells, with a cell seeding density of 30,000 cells/cm2 , were
      cultured with 0 to 2500 ug/mL of Mg or Mg-Ti in cell culture media for 24-72 h.
      Mg-Ti killed cells more effectively, where 1250 ug/mL of Mg-Ti killed cells
      completely by 24 h, while 2500 ug/mL of Mg killed nearly all cells, but not all.
      Killing due to particle corrosion occurred mostly during the first 24 h, and so
      the percent cell viability between 24 and 72 h showed not much variability.
      However, the measurement of live and dead cell numbers, over the timeframe of 24
      72 h, showed more insight, such as cell recovery. If particle concentrations were
      low, the number of live cells increased after 24 h, indicating cell
      proliferation. If particle concentrations were high, the number of live cells
      either remained steady or decreased, indicating cell quiescence or continued
      killing, respectively. Increase in the number of dead cells also indicated
      killing, while plateau meant discontinued killing. In addition, repeated killing
      of recovered cells exhibited the same dose-dependent killing profile as the
      initial experiment, implying little development of cell resistance to treatment.
      These results, together, show that osteosarcoma cells are susceptible to killing
      by way of exposure to corroding particles, showing highly effective killing using
      the galvanic couple of Mg-Ti. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res
      Part B: Appl Biomater, 2018.

PMID- 29635781
TI  - Interaction among variants in the SLC gene family (SLC6A14, SLC26A9, SLC11A1, and
      SLC9A3) and CFTR mutations with clinical markers of cystic fibrosis.
AB  - BACKGROUND: Cystic fibrosis (CF) is due to dysfunction of the CFTR channel and
      function of this channel is, in turn, affected by modifier genes that can impact
      the clinical phenotype. In this context, we analyzed the interaction among
      rs3788766*SLC6A14, rs7512462*SLC26A9, rs17235416*SLC11A1, and rs17563161*SLC9A3
      variants, CFTR mutations and 40 CF severity markers by the Multifactor
      Dimensionality Reduction (MDR) model. METHODS: A total of 164 patients with CF
      were included in the study. The variants in the modifier genes were identified by
      real-time PCR and the genotype of the CFTR gene in the diagnostic routine.
      Analysis of interaction between variants, CFTR mutations groupings and
      demographic, clinical and laboratory data were performed by the MDR. RESULTS:
      There were interaction between the rs3788766, rs7512462, rs17235416, and
      rs17563161 variants, and CFTR mutations with pancreatic insufficiency (PI), onset
      of digestive symptoms, and presence of mucoid Pseudomonas aeruginosa. Regarding
      PI, the interaction was observed for CFTR*rs17563161 (P-value = 0.015). Also, for
      onset of digestive symptoms the interaction was observed for
      CFTR*rs3788766*rs7512462*rs17235416*rs17563161 (P-value = 0.036). Considering the
      presence of mucoid P. aeruginosa, the interaction occurred for
      CFTR*rs3788766*rs7512462*rs17563161 (P-value = 0.035). CONCLUSION: Interaction
      between variants in the SLC family genes and the grouping for CFTR mutations were
      associated with PI, onset of digestive symptoms and mucoid P. aeruginosa, being
      important to determine one of the factors that may cause the diversity among the
      patients with CF.

PMID- 29635782
TI  - Group 9 Metallacyclopentadienes as Key Intermediates in [2+2+2] Alkyne
      Cyclotrimerizations. Insight from Activation Strain Analyses.
AB  - The intramolecular oxidative coupling converting a bis-acetylene complex of
      formula CpM (C2 H2 )2 (Cp=C5 H5- ; M=Co, Rh, Ir) into a 16-electron metallacycle
      is studied in silico. This reaction is paradigmatic in acetylene [2+2+2]
      cycloaddition to benzene catalyzed by CpM fragments, being the step with the
      highest activation energy, and thus affecting the whole catalysis. Our activation
      strain and quantitative molecular orbital (MO) analyses elucidate the mechanistic
      details and reveal why cobalt performs better than rhodium and iridium catalysts
      outlining general principles for rational design of catalysts to be used in these
      processes.

PMID- 29635783
TI  - Allergic reaction to 3 tattoo inks containing Pigment Yellow 65.

PMID- 29635784
TI  - Activation of T cells by dendritic cells exposed to a reference sensitizer:
      Towards a promising model to assess the allergenic potential of chemicals.
AB  - BACKGROUND: Low molecular weight chemicals constitute one of the major causes of
      occupational allergies. European legislation on chemicals recommends limiting the
      use of in vivo models for assessing the sensitizing potential of chemicals, and
      encourages the development of integrated alternative methods. An in vitro mouse
      model of bone marrow-derived dendritic cells (BMDCs) that showed good accuracy
      (75%) and sensitivity (69%) has previously been developed to assess the
      sensitizing potential of chemicals. OBJECTIVE: To assess the ability of BMDCs to
      activate T cells (TCs) in vitro. METHODS: BMDCs pre-exposed to the reference
      sensitizer ammonium hexachloroplatinate (AHCP) were co-cultured with different
      subpopulations of TCs. TC activation was assessed by surface marker expression,
      proliferation, and cytokine release. RESULTS: The results showed significant
      activation of TCs co-cultured with dendritic cells pre-exposed to AHCP as
      evaluated by CD124 expression, proliferation, and cytokine secretion. Moreover,
      the response of TCs appeared to be Th2-oriented. Naive TCs were shown to be
      involved in this response, and the removal of regulatory TCs did not improve the
      cell response. CONCLUSIONS: The BMDCs used in this previously developed model
      appear to have the ability to activate TCs, confirming that the BMDC model
      represents a reliable assay for assessing the sensitizing potential of chemicals.

PMID- 29635785
TI  - From Exploration to Instruction: Children Learn From Exploration and Tailor Their
      Demonstrations to Observers' Goals and Competence.
AB  - This study investigated whether children learn from exploration and act as
      effective informants by providing informative demonstrations tailored to
      observers' goals and competence. Children (4.0-6.9 years, N = 98) explored a
      causally ambiguous toy to discover its causal structure and then demonstrated the
      toy to a naive observer. Children provided more costly and informative evidence
      when the observer wanted to learn about the toy than observe its effects
      (Experiment 1) and when the observer was ordinary than exceptionally intelligent
      (Experiment 2). Relative to the evidence they generated during exploration,
      children produced fewer, less costly actions when the observer wanted or needed
      less evidence. Children understand the difference between acting-to-learn and
      acting-to-inform; after learning from exploration, they consider others' goals
      and competence to provide "uninstructed instruction".

PMID- 29635786
TI  - It's All Been Done Before: Rethinking Objectivity and Values in Public Sociology
      Debates.

PMID- 29635787
TI  - Effect of centrally acting angiotensin converting enzyme inhibitor on the
      exercise-induced increases in muscle sympathetic nerve activity.
AB  - KEY POINTS: The arterial baroreflex's operating point pressure is reset upwards
      and rightwards from rest in direct relation to the increases in dynamic exercise
      intensity. The intraneural pathways and signalling mechanisms that lead to
      upwards and rightwards resetting of the operating point pressure, and hence the
      increases in central sympathetic outflow during exercise, remain to be
      identified. We tested the hypothesis that the central production of angiotensin
      II during dynamic exercise mediates the increases in sympathetic outflow and,
      therefore, the arterial baroreflex operating point pressure resetting during
      acute and prolonged dynamic exercise. The results identify that perindopril, a
      centrally acting angiotensin converting enzyme inhibitor, markedly attenuates the
      central sympathetic outflow during acute and prolonged dynamic exercise.
      ABSTRACT: We tested the hypothesis that the signalling mechanisms associated with
      the dynamic exercise intensity related increases in muscle sympathetic nerve
      activity (MSNA) and arterial baroreflex resetting during exercise are located
      within the central nervous system. Participants performed three randomly ordered
      trials of 70 degrees  upright back-supported dynamic leg cycling after ingestion
      of placebo and two different lipid soluble angiotensin converting enzyme
      inhibitors (ACEi): perindopril (high lipid solubility), captopril (low lipid
      solubility). Repeated measurements of whole venous blood (n = 8), MSNA (n = 7)
      and arterial blood pressures (n = 14) were obtained at rest and during an acute
      (SS1) and prolonged (SS2) bout of steady state dynamic exercise. Arterial
      baroreflex function curves were modelled at rest and during exercise. Peripheral
      venous superoxide concentrations measured by electron spin resonance spectroscopy
      were elevated during exercise and were not altered by ACEi at rest (P >= 0.4) or
      during exercise (P >= 0.3). Baseline MSNA and mean arterial pressure were
      unchanged at rest (P >= 0.1; P >= 0.8, respectively). However, during both SS1
      and SS2, the centrally acting ACEi perindopril attenuated MSNA compared to
      captopril and the placebo (P < 0.05). Arterial pressures at the operating point
      and threshold pressures were decreased with perindopril from baseline to SS1 with
      no further changes in the operating point pressure during SS2 under all three
      conditions. These data suggest that centrally acting ACEi is significantly more
      effective at attenuating the increase in the acute and prolonged exercise-induced
      increases in MSNA.

PMID- 29635788
TI  - Clinical findings and survival time in dogs with advanced heart failure.
AB  - BACKGROUND: Dogs with advanced heart failure are a clinical challenge for
      veterinarians but there are no studies reporting clinical features and outcome of
      this population. HYPOTHESIS/OBJECTIVES: To describe clinical findings and outcome
      of dogs with advanced heart failure caused by degenerative mitral valve disease
      (DMVD). ANIMALS: Fifty-four dogs with advanced heart failure because of DMVD.
      METHODS: For study purposes, advanced heart failure was defined as recurrence of
      congestive heart failure signs despite receiving the initially prescribed dose of
      pimobendan, angiotensin-converting-enzyme inhibitor (ACEI), and furosemide >4
      mg/kg/day. Data were collected for the time of diagnosis of Stage C heart failure
      and time of diagnosis of advanced heart failure. Date of death was recorded.
      RESULTS: At the diagnosis of advanced heart failure, doses of pimobendan (n =
      30), furosemide (n = 28), ACEI (n = 13), and spironolactone (n = 4) were
      increased, with >=1 new medications added in most dogs. After initial diagnosis
      of advanced heart failure, 38 (70%) dogs had additional medications adjustments
      (median = 2 [range, 0-27]), with the final total medication number ranging from 2
      10 (median = 5). Median survival time after diagnosis of advanced heart failure
      was 281 days (range, 3-885 days). Dogs receiving a furosemide dose >6.70
      mg/kg/day had significantly longer median survival times (402 days [range, 3-885
      days] versus 129 days [range 9-853 days]; P = .017). CONCLUSIONS AND CLINICAL
      IMPORTANCE: Dogs with advanced heart failure can have relatively long survival
      times. Higher furosemide dose and non-hospitalization were associated with longer
      survival.

PMID- 29635789
TI  - Robust analysis of stepped wedge trials using cluster-level summaries within
      periods.
AB  - In stepped-wedge trials (SWTs), the intervention is rolled out in a random order
      over more than 1 time-period. SWTs are often analysed using mixed-effects models
      that require strong assumptions and may be inappropriate when the number of
      clusters is small. We propose a non-parametric within-period method to analyse
      SWTs. This method estimates the intervention effect by comparing intervention and
      control conditions in a given period using cluster-level data corresponding to
      exposure. The within-period intervention effects are combined with an inverse
      variance-weighted average, and permutation tests are used. We present an example
      and, using simulated data, compared the method to (1) a parametric cluster-level
      within-period method, (2) the most commonly used mixed-effects model, and (3) a
      more flexible mixed-effects model. We simulated scenarios where period effects
      were common to all clusters, and when they varied according to a distribution
      informed by routinely collected health data. The non-parametric within-period
      method provided unbiased intervention effect estimates with correct confidence
      interval coverage for all scenarios. The parametric within-period method produced
      confidence intervals with low coverage for most scenarios. The mixed-effects
      models' confidence intervals had low coverage when period effects varied between
      clusters but had greater power than the non-parametric within-period method when
      period effects were common to all clusters. The non-parametric within-period
      method is a robust method for analysing SWT. The method could be used by trial
      statisticians who want to emphasise that the SWT is a randomised trial, in the
      common position of being uncertain about whether data will meet the assumptions
      necessary for mixed-effect models.

PMID- 29635790
TI  - Popolohuanones G - I, Dimeric Sesquiterpene Quinones with IL-6 Inhibitory
      Activity from the Marine Sponge Dactylospongia elegans.
AB  - Chemical investigation of the marine sponge Dactylospongia elegans, collected
      from the South China Sea, afforded three new dimeric sesquiterpene quinones,
      popolohuanones G - I (1 - 3), together with two known analogs, popolohuanones B
      (4) and C (5). The new structures were determined by HR-ESI-MS and 1D- and 2D-NMR
      analyses. All the five compounds showed no cytotoxic activity against five human
      cancer cell lines, while popolohuanone H (2) showed potent inhibitory activity
      against IL-6, an inflammatory cytokine, at the concentration of 10 MUm.

PMID- 29635791
TI  - Fecal bacterial diversity of wild Sichuan snub-nosed monkeys (Rhinopithecus
      roxellana).
AB  - The gastrointestinal tract of primates harbors a complex microbial community,
      playing an essential role in the degradation of otherwise indigestible structural
      carbohydrates. The phylogenetic and functional diversity of the bacterial
      community in the feces as a surrogate for the gastrointestinal tract of wild
      Sichuan snub-nosed monkeys (Rhinopithecus roxellana, N = 6) was characterized
      based on sequence analysis of 16S rRNA genes. A sex comparison was conducted,
      with a prior hypothesis that the abundances of the bacterial taxa and/or
      functional categories associated with energy and nutrient metabolism would be
      higher in adult females (N = 3) due to the higher reproductive costs compared to
      adult males (N = 3). Ten phyla were identified in all samples, among which
      Bacteroidetes and Firmicutes were the predominant. Included in the above two
      phyla, the members of Prevotellaceae (Prevotella in particular) and
      Ruminococcaceae were highly abundant, which are common bacteria in the
      gastrointestinal tract of primates and can degrade various structural
      carbohydrates such as cellulose, hemicellulose, and pectin. This functionality
      was in line with the high abundances of the metagenomes associated with
      carbohydrate metabolism. Consistent with our hypothesis, the abundances of the
      metagenomes associated with energy metabolism, folding/sorting and degradation,
      glycan biosynthesis and metabolism, and metabolism of amino acids were higher in
      adult females relative to adult males. Sex differences were also detected in the
      bacterial community structure, although no sex differences in the proportions of
      any bacterial taxa were found likely due to the small sample size. These results
      suggested that gastrointestinal bacterial communities may aid adult females in
      increasing energy and nutrition utilization efficiencies compared to adult males.
      Fecal bacterial communities were found to be more similar between individuals in
      adult females than in adult males. Our study presented the first examination of
      the fecal bacterial diversity of a little-studied, endangered foregut fermenter.

PMID- 29635792
TI  - Haste makes waste-Should current guideline recommendations for initiation of
      renal replacement therapy for acute kidney injury be changed?
AB  - There is broad consensus among guideline organizations that renal replacement
      therapy (RRT) should not be delayed in case of life-threatening conditions.
      However, in case of severe acute kidney injury (AKI) without these conditions, it
      is unclear whether immediate RRT has an advantage over delayed RRT. Two recently
      published randomized controlled trials (AKIKI and ELAIN) with seemingly opposite
      results have reignited the discussion whether guideline recommendations on
      initiation strategies in severe AKI should be adapted. This editorial discusses
      RRT initiation strategies in severe AKI, based on recent literature and
      highlights the potential advantages and disadvantages of immediate vs delayed
      start. Overall, evidence in favor of immediate compared to delayed strategies is
      sparse and there is wide heterogeneity across studies making it difficult to draw
      firm conclusions. RRT should not be delayed in case of refractory hyperkalemia,
      severe metabolic acidosis or pulmonary edema resistant to diuretics. In all other
      cases, a delayed strategy seems justified and might enhance renal recovery. RRT
      is not a "it doesn't hurt to try" technique and can expose the patient to a
      higher risk of bleeding, hemodynamic problems, under-dosing of antibiotics, loss
      of nutrients, catheter-related complications and the uncertain effects of blood
      membrane interactions. There is no compelling reason to change current guideline
      recommendations and research focus should shift toward the development of
      algorithms as a decision aid tool for RRT initiation in severe AKI.

PMID- 29635793
TI  - Role of alkyl silatranes as plant growth regulators: comparative substitution
      effect on root and shoot development of wheat and maize.
AB  - BACKGROUND: The present investigation reports the stimulating effects of
      different substituted alkyl silatranes (3a-3e) on the early seedling growth of
      wheat (Triticum aestivum) and maize (Zea mays). Seeds of these plants were
      exposed to six different concentrations (0, 10, 50, 100, 200 and 500 umol L-1 ).
      The results revealed that different substitutions (3a-3e) had different effects
      on root and shoot elongation. Silatranes (3a-3e) were synthesized employing
      microwave irradiation by a solvent-mediated transesterification reaction, thereby
      reducing reaction times from several hours under conventional reflux conditions
      to 15 min under microwave irradiation. RESULTS: It was of interest that the
      effect of these silatranes did not show a dose-dependent relationship but an
      optimum concentration, which was 100 umol L-1 for maize and 200 umol L-1 for
      wheat. gamma-Aminopropyl silatranes (3b and 3e) gave the best results in maize,
      whereas gamma-chloropropyl silatrane (3a) was most efficient for wheat at these
      optimum concentrations. CONCLUSION: All the synthesized silatranes were effective
      in promoting root and shoot growth of wheat and maize. Furthermore, an efficient
      green microwave methodology was successful for the synthesis of silatranes. These
      observations pave the way for silatranes as efficient plant growth regulators for
      crops. (c) 2018 Society of Chemical Industry.

PMID- 29635794
TI  - Integration of nicotinic acid adenine dinucleotide phosphate (NAADP)-dependent
      calcium signalling.
AB  - Nicotinic acid adenine dinucleotide phosphate (NAADP) is currently the most
      potent endogenous Ca2+ mobilizing second messenger. Upon specific extracellular
      stimulation, rapid production of NAADP has been observed in different cell types
      from sea urchin eggs to mammalian cells. More than 20 years after the discovery
      of NAADP, there is still controversy surrounding its metabolism and target
      receptors/ion channels and organelles. This article briefly reviews recent
      developments in the NAADP field. Besides the metabolism of NAADP, this review
      focuses on assumed organelles and putative targets, e.g. ion channels, with
      special emphasis on ryanodine receptor type 1 (RyR1) and two-pore channels
      (TPCs). The role of NAADP as a Ca2+ trigger is also discussed and the importance
      of NAADP in the formation of initial Ca2+ microdomains is highlighted.

PMID- 29635795
TI  - Design and characterization of tissue-mimicking gel phantoms for diffusion
      kurtosis imaging.
AB  - PURPOSE: The aim of this work was to create tissue-mimicking gel phantoms
      appropriate for diffusion kurtosis imaging (DKI) for quality assurance, protocol
      optimization, and sequence development. METHODS: A range of agar, agarose, and
      polyvinyl alcohol phantoms with concentrations ranging from 1.0% to 3.5%, 0.5% to
      3.0%, and 10% to 20%, respectively, and up to 3 g of glass microspheres per 100
      ml were created. Diffusion coefficients, excess kurtosis values, and relaxation
      rates were experimentally determined. RESULTS: The kurtosis values for the plain
      gels ranged from 0.05 with 95% confidence interval (CI) of (0.029,0.071) to
      0.216(0.185,0.246), well below the kurtosis values reported in the literature for
      various tissues. The addition of glass microspheres increased the kurtosis of the
      gels with values up to 0.523(0.465,0.581) observed for gels with the highest
      concentration of microspheres. Repeat scans of some of the gels after more than 6
      months of storage at room temperature indicate changes in the diffusion
      parameters of less than 10%. The addition of the glass microspheres reduces the
      apparent diffusion coefficients (ADCs) and increases the longitudinal and
      transverse relaxation rates, but the values remain comparable to those for plain
      gels and tissue, with ADCs observed ranging from 818(585,1053) * 10-6  mm2 /s to
      2257(2118,2296) * 10-6  mm2 /s, R1 values ranging from 0.34(0.32,0.35) 1/s to
      0.51(0.50,0.52) 1/s, and R2 values ranging from 9.69(9.34,10.04) 1/s to
      33.07(27.10, 39.04) 1/s. CONCLUSIONS: Glass microspheres can be used to
      effectively modify diffusion properties of gel phantoms and achieve a range of
      kurtosis values comparable to those reported for a variety of tissues.

PMID- 29635796
TI  - Hierarchical MoS2 @TiO2 Heterojunctions for Enhanced Photocatalytic Performance
      and Electrocatalytic Hydrogen Evolution.
AB  - Hierarchical MoS2 @TiO2 heterojunctions were synthesized through a one-step
      hydrothermal method by using protonic titanate nanosheets as the precursor. The
      TiO2 nanosheets prevent the aggregation of MoS2 and promote the carrier transfer
      efficiency, and thus enhance the photocatalytic and electrocatalytic activity of
      the nanostructured MoS2 . The obtained MoS2 @TiO2 has significantly enhanced
      photocatalytic activity in the degradation of rhodamine B (over 5.2 times
      compared with pure MoS2 ) and acetone (over 2.8 times compared with pure MoS2 ).
      MoS2 @TiO2 is also beneficial for electrocatalytic hydrogen evolution (26 times
      compared with pure MoS2 , based on the cathodic current density). This work
      offers a promising way to prevent the self-aggregation of MoS2 and provides a new
      insight for the design of heterojunctions for materials with lattice mismatches.

PMID- 29635798
TI  - International Alcohol Control Study: Analyses from the first wave.

PMID- 29635797
TI  - Cardiac papillary fibroelastoma originating from the left ventricular septum.

PMID- 29635799
TI  - Social health insurance in Nepal: A health system departure toward the universal
      health coverage.
AB  - The World Health Organization has identified universal health coverage (UHC) as a
      key approach in reducing equity gaps in a country, and the social health
      insurance (SHI) has been recommended as an important strategy toward it. This
      article aims to analyze the design, expected benefits and challenges of realizing
      the goals of UHC through the recently launched SHI in Nepal. On top of the
      earlier free health-care policy and several other vertical schemes, the SHI
      scheme was implemented in 2016 and has reached population coverage of 5% in the
      implemented districts in just within a year of implementation. However, to
      achieve UHC in Nepal, in addition to operationalizing the scheme, several other
      requirements must be dealt simultaneously such as efficient health-care delivery
      system, adequate human resources for health, a strong information system,
      improved transparency and accountability, and a balanced mix of the preventive,
      health promotion, curative, and rehabilitative services including actions to
      address the social determinants of health. The article notes that strong
      political commitment and persistent efforts are the key lessons learnt from
      countries achieving progressive UHC through SHI.

PMID- 29635800
TI  - Spring weather conditions influence breeding phenology and reproductive success
      in sympatric bat populations.
AB  - Climate is known to influence breeding phenology and reproductive success in
      temperate-zone bats, but long-term population level studies and interspecific
      comparisons are rare. Investigating the extent to which intrinsic (i.e. age), and
      extrinsic (i.e. spring weather conditions), factors influence such key
      demographic parameters as the proportion of females becoming pregnant, or
      completing lactation, each breeding season, is vital to understanding of bat
      population ecology and life-history traits. Using data from 12 breeding seasons
      (2006-2017), encompassing the reproductive histories of 623 Myotis daubentonii
      and 436 Myotis nattereri adult females, we compare rates of recruitment to the
      breeding population and show that these species differ in their relative
      sensitivity to environmental conditions and climatic variation, affecting annual
      reproductive success at the population level. We demonstrate that (1) spring
      weather conditions influence breeding phenology, with warm, dry and calm
      conditions leading to earlier parturition dates and advanced juvenile
      development, whilst cold, wet and windy weather delays birth timing and juvenile
      growth; (2) reproductive rates in first-year females are influenced by spring
      weather conditions in that breeding season and in the preceding breeding season
      when each cohort was born. Pregnancy and lactation rates were both higher when
      favourable spring foraging conditions were more prevalent; (3) reproductive
      success increases with age in both species, but at different rates; (4)
      reproductive rates were consistently higher, and showed less interannual
      variation, in second-year and older M. daubentonii (mean 91.55% +/- 0.05 SD) than
      M. nattereri (mean 72.74% +/- 0.15 SD); (5) estimates of reproductive success at
      the population level were highly correlated with the size of the juvenile cohort
      recorded each breeding season. Improving understanding of the influence of
      environmental conditions, especially extreme climatic fluctuations, and the
      identification of critical periods (i.e. spring for reproductive female bats in
      temperate zones), which have disproportionate and lasting impacts on breeding
      phenology and reproductive success at a population level, is critical for
      improving predictions of the likely impact of climate change on bat populations.

PMID- 29635801
TI  - Drug reaction with eosinophilia and systemic symptoms syndrome induced by
      benznidazole.

PMID- 29635804
TI  - Do the potential benefits outweigh the risks? An update on the use of ziconotide
      in clinical practice.
AB  - Ziconotide is a selective and potent blocker of N-type voltage-gated calcium
      channels. It was approved by the Food and Drug Administration in 2004 and by the
      European Medicines Agency in 2005 for the treatment of severe chronic pain in
      patients needing intrathecal analgesia (ITA). The aim of this paper is to provide
      a practitioner-oriented, educational, narrative, up-to-date review on the use of
      ziconotide in clinical pain medicine. Of special concern regarding safety is the
      partial incongruity between dosing statements in the Summary of Product
      Characteristics and novel low-dosage, slow uptitration recommendations. Even
      though ziconotide has obvious advantages compared to opioids, pain practitioners
      pondering the use of ziconotide nonetheless have to balance its proved potential
      analgesic effect against its neurological side effects, with special
      consideration being given to dosing and neuropsychiatric dangers. Using a seesaw
      analogy, the paper discusses what factors pain physicians should weigh in when
      considering ziconotide as ITA drug, the non-opioid advantages of ziconotide being
      counterbalanced by its potential psychiatric side effects. Ziconotide is an
      important part of the armamentarium of modern interventional pain medicine. If
      ITA is deemed necessary, ziconotide is a rational alternative, at least in
      chronic (neuropathic) non-cancer pain. However, in many European countries,
      ziconotide treatment is only available in a few (if any) centres. The safety
      profile of ziconotide is not fundamentally more worrying than that of opioids or
      cannabinoids; it is just different. This paper provides a concise, up-to-date and
      clinically-oriented summary of the use of ziconotide in clinical practice, not
      least concerning safety and dosage issues.

PMID- 29635803
TI  - Stimulating effect of palmitate and insulin on cell migration and proliferation
      in PNT1A and PC3 prostate cells: Counteracting role of metformin.
AB  - BACKGROUND: A potential association between obesity and prostate cancer has been
      proposed. Metformin, an antidiabetes drug, has antiproliferative effects being
      proposed for cancer treatment. However, under intense proliferative stimulation
      conditions such as those found in obesity, its efficacy is still uncertain. Thus,
      we analyzed the effects of saturated fatty acid and/or insulin under high
      concentrations, with or without metformin, on the proliferation and migration of
      prostate cells. METHODS: Human prostate epithelial cell lines non-tumor (PNT1A)
      and tumor (PC3) were treated with control media (DMEM, C), palmitate (100 uM,
      HF), and/or insulin (50 uU, HI) with or without metformin (100 uM) for 24 or 48
      h. RESULTS: Both PNT1A and PC3 cells had greater proliferation when treated with
      HF, while HI treatment stimulated only PNT1A. Metformin inhibited cell
      proliferation caused by HF in both cell lines, but it did not block the
      proliferative action of HI in PNT1A cells. PNT1A increased cell migration after
      all treatments, while only HF influenced PC3; metformin inhibited the migration
      stimulated by all obese microenvironments. Both HF and HI treatments in PNT1A and
      HF treatment in PC3 augmented vimentin expression, resulting in a higher
      epithelial-mesenchymal transition (which, in turn, could influence cell
      migration). Metformin inhibited vimentin expression in both normal and tumor
      cells. Although HF treatment had increased AMPK activation, it also increased the
      levels of activated ERK1/2, which could be responsible for high cell
      proliferation in both cell lines. In contrast, HI decreased AMPK activation in
      both cell lines, whereas it increased ERK1/2 levels in PNT1A and decreased them
      in PC3 (reflecting greater cell proliferation only in non-tumor cells). Metformin
      maintained high activation of AMPK and decreased ERK1/2 levels after HF in both
      cell lines and only after HI in PNT1A, which was able to decrease the cell
      proliferation triggered by these treatments. CONCLUSIONS: Higher concentrations
      of palmitate on PC3 cells and palmitate and insulin on PNT1A cells stimulate
      cellular activities that could favor cancer progression. Metformin inhibited most
      of these stimuli, showing the efficacy of this drug for cancer adjuvant therapy
      in obese patients (a group at increased risk for the development of prostrate
      cancer).

PMID- 29635802
TI  - Prevalence of contact allergy to metals in the European general population with a
      focus on nickel and piercings: The EDEN Fragrance Study.
AB  - BACKGROUND: Studies on sensitization to metals in the general population are
      scarce. OBJECTIVES: To determine the prevalence of sensitization to metals in the
      general population, and factors associated with nickel sensitization. METHODS: In
      5 European countries (The Netherlands, Germany, Italy, Portugal and Sweden), a
      random sample (N = 3119) from the general population (aged 18-74 years) was patch
      tested and interviewed by use of a questionnaire on exposure to metals, piercing,
      and jewellery. RESULTS: Overall, the age-standardized prevalences of
      sensitization to nickel, cobalt and chromium were, respectively, 14.5%, 2.1%, and
      0.8%. The highest prevalence of nickel sensitization was seen in Portugal (18.5%)
      and the lowest (8.3%) in Sweden. The prevalence of cobalt sensitization varied
      between 3.8% (The Netherlands) and 0.9% (Italy), and the prevalence of chromium
      sensitization varied between 1.3% (Portugal) and 0.2% (Sweden). Significant
      associations were observed between nickel allergy and female sex (odds ratio [OR]
      5.19; 95% confidence interval [95%CI]: 3.99-6.74), past piercing use (OR 3.86;
      95%CI: 2.85-5.24), and currently having >=3 piercings (OR 5.58; 95%CI: 4.02
      7.76). CONCLUSIONS: The prevalence of sensitization to metals in the European
      general population was high, mostly because of nickel. The lowest prevalence of
      contact allergy to nickel and chromium observed in Sweden supports the
      effectiveness of long-standing regulation.

PMID- 29635805
TI  - Ge2 Sb2 Te5 -Based Tunable Perfect Absorber Cavity with Phase Singularity at
      Visible Frequencies.
AB  - The metal-dielectric stacks-based asymmetric Fabry-Perot (F-P) cavity systems
      have recently attracted much interest from the scientific community for realizing
      perfect absorption over the spectral bands from visible to infrared since they
      possess a lithography-free design that is cost-effective and scalable. This study
      experimentally demonstrates an asymmetric F-P cavity system for achieving tunable
      wide angle perfect absorption and phase singularity. The proposed system shows
      tunable multiband perfect absorption in the visible spectral region by
      incorporating an ultrathin layer of phase change material such as Ge2 Sb2 Te5
      (GST) in the stack. The system shows multi-narrowband perfect absorption with a
      maximum of 99.8% at a specific incident angle and polarization state when the GST
      is in amorphous phase; however, the absorption bands blueshift and broaden after
      switching to the crystalline phase. More importantly, the proposed scheme shows
      tunable phase singularity at the reflection-less point. The obtained tunable
      perfect absorption and abrupt phase change are solely due to the presence of a
      highly absorbing ultrathin layer of GST in the stack. Experimental results are
      validated using an analytical simulation model based on a transfer matrix method.
      The proposed scheme could find potential applications in active photonic devices
      such as phase-sensitive biosensors and absorption filters.

PMID- 29635806
TI  - Has aerobic exercise effect on pain perception in persons with migraine and
      coexisting tension-type headache and neck pain? A randomized, controlled,
      clinical trial.
AB  - BACKGROUND: A large subset of persons with migraine suffers from coexisting
      tension-type headache and neck pain which may adversely affect the prognosis of
      migraine. Aerobic exercise has been shown to decrease migraine burden in these
      persons. Therefore, the aim of this study was to investigate whether the effect
      of aerobic exercise in persons with migraine and coexisting tension-type headache
      and neck pain can be explained by changes in pain perception. METHOD: Seventy
      consecutively recruited persons with migraine and coexisting tension-type
      headache and neck pain were randomized into exercise group or control group.
      Aerobic exercise consisted of bike/cross-trainer/brisk walking for 45 min, three
      times/week for 3 months. Controls continued their usual daily activities.
      Pericranial tenderness, pain thresholds, supra-thresholds and temporal summation
      were assessed at baseline, after treatment and at follow-up (6 months from
      baseline). RESULTS: Fifty-two persons with migraine and coexisting tension-type
      headache and neck pain completed the study. Aerobic exercise did not induce
      consistent changes in nociceptive pathways measured by pericranial tenderness,
      pressure pain thresholds and sensitivity to electrical stimulation. CONCLUSION:
      The effect of aerobic exercise cannot be explained by measurable effects on the
      pain modulation system. Thus, the positive effect on migraine burden may rather
      be explained by positive alteration of avoidance behaviour. Aerobic exercise can
      be recommended as a safe and inexpensive migraine treatment strategy.
      SIGNIFICANCE: This study adds further knowledge about the positive effect of
      aerobic exercise for persons with migraine and coexisting tension-type headache
      and neck pain. This effect cannot be measured by changes in pain modulation, but
      may rather be explained by positive alteration of avoidance behaviour.

PMID- 29635807
TI  - The relationship between masking and short-term consolidation during recall from
      visual working memory.
AB  - The presentation of a similar but irrelevant stimulus immediately following
      presentation of a memory item is called masking. Masking is known to reduce
      performance on working memory tests. This is the type of memory used to hold
      information in mind for brief periods of time for use in ongoing cognition. Two
      approaches to understanding masking effects have been proposed in different
      literatures. Working memory researchers often assume that the reduction in
      working memory performance after masking is because masking interferes with a
      transient sensory representation that is needed to complete consolidation into a
      working memory state. Researchers focused on the attentional blink, a finding
      that attention cannot be directed to new stimuli during working memory
      consolidation, have an alternative theory. Attentional blink researchers assume
      that masking slows the short-term consolidation process, thereby extending the
      length of the attentional blink. In two experiments, we contrast these two
      approaches to explaining masking effects and investigate the validity of both
      hypotheses. Some aspects of both approaches are validated, but neither
      theoretical perspective alone sufficiently explains the entire pattern of
      results.

PMID- 29635808
TI  - Cancer drug shortages: Awareness and perspectives from a representative sample of
      the US population.
AB  - BACKGROUND: Although cancer drug shortages are a persistent problem in oncology,
      little is known about the awareness and perspectives of the US population with
      respect to shortages. METHODS: In 2016, we administered a 13-item cross-sectional
      survey to 420 respondents who were randomly selected from an online, probability
      based sample demographically representative of the adult US population with
      respect to sex, age, race/ethnicity, education, geography, and income. Analyses
      applied poststratification sampling weights to draw national inferences. RESULTS:
      Overall, 16% of respondents reported being aware of drug shortages. Those with a
      personal history of cancer were more likely to be aware (31% vs 14% [P = .03]).
      In the overall cohort, most reported wanting to be informed about a substitution
      due to shortage: 87% and 82% for major or minor differences in efficacy, and 87%
      and 83% for major or minor differences in side effects. Most also reported they
      would transfer care to avoid a substitution: 72% for major differences in
      efficacy, and 61% for major differences in side effects. Black respondents, the
      uninsured, the unemployed, those with lower income, and the less well-educated
      were all less likely to report that they would transfer care to avoid major
      differences in efficacy (all P < .05). CONCLUSION: These data suggest that the US
      population is largely unaware of cancer drug shortages. Moreover, if being
      treated for cancer, most people would want to know about drug substitutions, even
      if it were to result in only minor differences in efficacy or side effects. With
      more significant differences, many would transfer care. Cancer 2018;124:2205-11.
      (c) 2018 American Cancer Society.

PMID- 29635809
TI  - Gingival crevicular fluid and salivary resistin and tumor necrosis factor-alpha
      levels in obese children with gingivitis.
AB  - BACKGROUND: This study aimed to evaluate the levels of resistin and tumor
      necrosis factor-alpha (TNF-alpha) in gingival crevicular fluid (GCF) and saliva
      of obese children with gingivitis. METHODS: One-hundred and thirty children (65
      obese and 65 normal weight; age range 8 to 12 years) were recruited for the
      study. The children were classified into four subgroups based on their body mass
      and periodontal status; 1) obese children with gingivitis (OG, n = 33); 2) obese
      children with healthy periodontium (OH, n = 32); 3) normal weight children with
      gingivitis (NWG, n = 32); 4) normal weight children with healthy periodontium
      (NWH, n = 33). Body mass index (BMI) percentile, probing pocket depth (PPD),
      gingival index (GI), and plaque index (PI) were recorded. Resistin and TNF-alpha
      were analyzed in GCF and saliva samples by ELISA. RESULTS: Obese children had
      higher BMI percentiles than normal weight children (p < 0.0001). PPD, GI, PI, GCF
      volume, GCF, and salivary resistin and TNF-alpha levels were similar between
      obese and normal weight children (P > 0.05). OG and NWG subgroups had
      significantly higher GI, PI, GCF volume, GCF resistin total amounts, and salivary
      resistin concentrations but lower GCF resistin and TNF-alpha concentrations than
      OH and NWH (P < 0.0001 for all). GCF resistin total amounts were positively
      correlated with GI, PI, and GCF TNF-alpha total amounts (P < 0.05). CONCLUSIONS:
      To our knowledge, this is the first study evaluated the levels of resistin in GCF
      and saliva of children. Obesity is not associated with GCF and salivary resistin
      and TNF-alpha levels in children in the presence of gingival inflammation.

PMID- 29635810
TI  - Earlier use of androgen receptor-axis-targeted drugs may improve overall survival
      in patients with non-metastatic castration-resistant prostate cancer.
AB  - BACKGROUND: To evaluate the role of androgen receptor-axis-targeted drugs (ARAT)
      in non-metastatic castration-resistant prostate cancer (nmCRPC) versus mCRPC.
      METHODS: Chemotherapy-naive patients (n = 114) with CRPC who had no metastasis at
      the time of diagnosis were included in this retrospective study. All patients
      were treated with ARAT at Jikei University and its affiliated hospitals from July
      2014 to March 2017. The patients were stratified into nmCRPC (n = 81) and mCRPC
      (n = 33) groups according to their metastatic status at ARAT induction. The
      primary outcome measure was difference in overall survival (OS) between groups
      from the time of CRPC diagnosis. The patients were compared for progression-free
      survival (PFS) and prostate-specific antigen (PSA) response. The predictors of OS
      were explored by a multivariate Cox model. RESULTS: The baseline demographics did
      not differ significantly between the groups. The median observation period from
      the diagnosis of CRPC was 24.5 months (range: 3-135) and 20 months (range: 1-66)
      in nmCRPC and mCRPC groups, respectively. The nmCRPC group demonstrated better OS
      from the time of diagnosis of CRPC in Kaplan-Meier analysis than mCRPC group (86
      months vs 40 months; P = 0.004), with similar results obtained for PFS (P =
      0.048) and PSA response (P = 0.0014). Multivariate analysis demonstrated non
      metastatic status, low PSA, and long PSA doubling time (PSADT) at ARAT induction
      as the significant predictors of longer OS (P = 0.044, 0.0001, and 0.026,
      respectively). CONCLUSIONS: Early use of ARAT may improve OS, PFS, and PSA
      response in CRPC. Larger, prospective studies will be required to confirm our
      findings.

PMID- 29635811
TI  - Group-level competition influences urinary steroid hormones among wild red-tailed
      monkeys, indicating energetic costs.
AB  - Various theories emphasize that intergroup competition should affect intragroup
      cooperation and social relationships, especially if the cost of intergroup
      competition outweighs that of intragroup competition. This cost of intergroup
      competition may be quantified by changes in physiological status, such as in the
      steroid hormones cortisol (C) and testosterone (T), which rise or are depressed
      during periods of energetic stress, respectively. Here we tested for changes in
      urinary C and T after intergroup encounters (IGEs) among wild red-tailed monkeys
      (Cercopithecus ascanius), a species that experiences frequent intergroup feeding
      competition, at the Ngogo station in Kibale National Park, Uganda. We assayed 108
      urine samples, of which 36 were collected after IGEs, from 23 individuals in four
      social groups. Bayesian multilevel models controlling for various confounds
      revealed that IGEs increased C and decreased T relative to baseline, consistent
      with an energetic cost to IGEs. The C change was more apparent in samples
      collected early after IGEs, suggesting an anticipatory increase, whereas the T
      change was stronger in later samples, suggesting sustained energetic trade-offs.
      Hormone responses were not affected by the IGE outcome. This cost to intergroup
      competition, together with little evidence for intragroup competition in redtails
      and other guenons, establishes an interesting test case for theories emphasizing
      the effect of intergroup competition on intragroup cooperation.

PMID- 29635812
TI  - The Multidimensional Symptom Index: A new patient-reported outcome for pain
      phenotyping, prognosis and treatment decisions.
AB  - BACKGROUND: There are few patient-reported outcomes routinely used that capture
      frequency and interference of different pain-related symptoms on a single scale.
      The purpose of this study was to describe the development and initial validation
      of the new Multidimensional Symptom Index (MSI). METHODS: Items were generated
      from patient interviews of the experience of chronic pain. Health valuations were
      created from rankings of 82 healthy subjects for each of 120 symptom (*10) *
      frequency (*3) * interference (*4) combinations using preference-based health
      valuations (0-100). Ranks for each symptom combination were then used in scale
      scoring. A sample of 300 patients with acute or chronic pain subsequently
      completed the MSI and a battery of other tools. Exploratory (EFA) and
      Confirmatory (CFA) factor analyses were triangulated with theory to arrive at the
      factor structure. Convergent validity was tested against established measures.
      RESULTS: Health rankings resulted in scores of 0-12 for each of the 10 symptom
      types. Factor analyses revealed two factors: MSI Somatic Symptoms and MSI Non
      Somatic Symptoms. The MSI also quantified number of symptoms experienced (/10),
      mean frequency (/3) and mean interference (/4). The indices showed appropriate
      associations with the established PROs. CONCLUSIONS: The MSI is a new symptom
      focused PRO that allows patient phenotyping and may have value for screening,
      prognosis and evaluating change. SIGNIFICANCE: This article presents the
      development and psychometric properties of a new measure of pain and related
      symptom frequency and interference. This measure could aid clinicians in
      establishing clinically relevant pain phenotypes for screening, prognosis and
      treatment decisions.

PMID- 29635813
TI  - Successful merging of data from the United Network for Organ Sharing and the
      Pediatric Health Information System databases.
AB  - Data routinely collected through United Network for Organ Sharing (UNOS) lack the
      detailed information on medical resource utilization and treatment costs required
      to accomplish for center-level comparisons of quality of care and cost for
      pediatric heart transplantation. We aimed to overcome this limitation by merging
      UNOS with the Pediatric Health Information System (PHIS) database, an
      administrative database containing inpatient, emergency department, ambulatory
      surgery, and observation unit information from over 40 not-for-profit, tertiary
      care pediatric hospitals. Utilizing a probabilistic match based on center, date
      of birth, recipient gender, and transplant date within +/-2 days, more than 90%
      of eligible UNOS patients (N = 2264) were successfully merged to their
      corresponding PHIS records. Thirty-day and 1-year mortality rates observed for
      the merged cohort (3.2% and 9.0%, respectively) were compared with those
      previously reported for pediatric heart transplants, as were the significant
      predictors of increased mortality. These results demonstrate that the established
      UNOS-PHIS cohort will provide a valid platform for subsequent research aimed at
      identifying center-level differences that could be exploited to optimize quality
      of care while minimizing cost across institutions.

PMID- 29635814
TI  - An Optically Flat Conductive Outcoupler Using Core/Shell Ag/ZnO Nanochurros.
AB  - Transparent conductive electrodes (TCEs) featuring a smooth surface are
      indispensable for preserving pristine electrical characteristics in
      optoelectronic and transparent electronic devices. For high-efficiency organic
      light emitting diodes (OLEDs), a high outcoupling efficiency, which is crucial,
      is only achieved by incorporating a wavelength-scale undulating surface into a
      TCE layer, but this inevitably degrades device performance. Here, an optically
      flat, high-conductivity TCE composed of core/shell Ag/ZnO nanochurros (NCs) is
      reported embedded within a resin film on a polyethylene terephthalate substrate,
      simultaneously serving as an efficient outcoupler and a flexible substrate. The
      ZnO NCs are epitaxially grown on the {100} planes of a pentagonal Ag core and the
      length of ZnO shells is precisely controlled by the exposure time of Xe lamp.
      Unlike Ag nanowires films, the Ag/ZnO NCs films markedly boost the optical
      tunneling of light. Green-emitting OLEDs (2.78 * 3.5 mm2 ) fabricated with the
      Ag/ZnO TCE exhibit an 86% higher power efficiency at 1000 cd m-2 than ones with
      an Sn-doped indium oxide TCE. A full-vectorial electromagnetic simulation
      suggests the suppression of plasmonic absorption losses within their Ag cores.
      These results provide a feasibility of multifunctional TCEs with synthetically
      controlled core/shell nanomaterials toward the development of high-efficiency LED
      and solar cell devices.

PMID- 29635815
TI  - Psychosocial impact, perceived stress and learning effect in undergraduate dental
      students during transition from pre-clinical to clinical education.
AB  - INTRODUCTION: This study aimed to develop a suitable instrument for a
      comprehensive quantitative and qualitative assessment of perceived psychosocial
      impact, levels of stress and learning effect in undergraduate dental students
      during the transition from pre-clinical to clinical education. These findings
      might improve curricular structures and didactic organisation during this period.
      MATERIALS AND METHODS: At the beginning of their first clinical year,
      undergraduate dental students were asked to complete an anonymous forty-item
      questionnaire. Two hundred and seventy-six undergraduate dental students were
      willing to participate and completed the questionnaire and participated during
      the years 2011-2016. RESULTS: The response rate was between 45% and 96%.
      Correlational analysis (Spearman-Rho) in the field of psychosocial impact showed
      the dental teacher to be the most important multiplier of students' feelings. If
      the students feel that their teacher acts cooperatively, positive items increase
      and negative items decrease significantly (P < .0001). Also, students who report
      high levels of stress are affected significantly in their psychosocial
      interaction (P < .0001). Wilcoxon test yielded highest levels of stress in
      endodontology during the first weeks (P < .0001). During the same period, the
      greatest learning increment was seen for diagnostics and caries excavation.
      CONCLUSION: In conclusion, teaching of undergraduate dental students during the
      transition period from pre-clinical to clinical education can be positively
      influenced by a supportive learning environment and by specific chronological
      modifications in the curriculum. Students should start their clinical training
      with diagnostics, preventive dentistry and initial periodontal treatment. Due to
      high levels of perceived stress, endodontology should be introduced later in the
      clinical curriculum.

PMID- 29635817
TI  - Dipole moments of molecules with multi-reference character from optimally tuned
      range-separated density functional theory.
AB  - Dipole moment is the first nonzero moment of the charge density of neutral
      systems. If a density functional theory (DFT) method is able to yield accurate
      dipole moments, it should first provide an accurate geometry and then predict a
      reliable charge distribution for that geometry. In this respect, recent
      literatures have revealed that most DFT approximations work considerably better
      for single-reference molecules with respect to multi-reference ones, as may be
      expected from this fact that DFT utilizes a single configuration state function
      as reference function to represent the density. Putting together, it seems that
      as compared to the single-reference systems, situation is slightly more involved
      in the case of dipole moment calculations of multi-reference molecules. Effort to
      address this latter issue constitutes the cornerstone of the present
      investigation. To this end, we rely on a different approach where the new
      optimally (nonempirically) tuned range-separated hybrid density functionals (OT
      RSHs) without invoking any empirical fitting are proposed for predicting the
      dipole moments of multi-reference molecules containing both main-group elements
      and transition metals. We have scanned the controlling factors of OT-RSHs like
      short- and long-range exchange contributions and range-separation parameter with
      the aim of deriving the best performing models for the purpose. The obtained
      results unveil that, as compared to the standard range-separated density
      functionals, our newly developed OT-RSHs not only give an improved description on
      the dipole moments of the molecules with multi-reference character but also the
      quality of their predictions is better than other conventional and recently
      proposed DFT approximations. (c) 2018 Wiley Periodicals, Inc.

PMID- 29635816
TI  - Nutritional profiling of Eurasian woodcock meat: chemical composition and
      myoglobin characterization.
AB  - BACKGROUND: Meat from birds is a rich source of proteins for the human diet. In
      this framework, Eurasian woodcock (Scolopax rusticola L.), a medium-small wading
      bird hunted as game in many Eurasian countries, is considered one of the best
      meats for culinary purposes. Since the nutritional composition of Eurasian
      woodcock meat has not yet been reported, we decided to determine the nutritional
      profile of S. rusticola meat. RESULTS: Macronutrient components (proteins, lipids
      and fatty acids) were determined, as well as free and total amino acids, and
      compared with those of the common pheasant. Eurasian woodcock meat contains high
      levels of proteins and essential amino acids. The levels of unsaturated fatty
      acids represent a great contribution to the total lipid amount. Among
      polyunsaturated fatty acids, linoleic acid (C18:2, n-6) is the major essential
      fatty acid. Finally, we report the characterization of myoglobin (Mb) from
      Eurasian woodcock. CONCLUSION: The data revealed that meat from this bird could
      be a good source of quality raw proteins because of its amino acid composition,
      and it had a low lipid content. On the other hand, Mb characterization might be
      of benefit to the meat industry, by providing useful information for the
      determination of species-specific differences in meat from birds. (c) 2018
      Society of Chemical Industry.

PMID- 29635818
TI  - The microRNA-1908 up-regulation in the peripheral blood cells impairs amyloid
      clearance by targeting ApoE.
AB  - OBJECTIVE: To give a new insight into the mechanism of ApoE dysregulation and
      microRNA-1908 in Alzheimer's disease (AD). METHODS: Plasma ApoE levels were
      measured in 20 AD patients and 20 healthy controls. THP-1 was maintained in
      RPMI1640 with 10% fetal bovine serum. Quantitative real-time polymerase chain
      reaction was performed to detect 13-microRNA and ApoE mRNA in cultured cell
      lines. Enzyme-linked immunosorbent assay was used to measure human ApoE in the
      plasma or culture medium of cell lines and also used to quantify the human
      Abeta42 in the culture medium of cell lines. RESULTS: We found plasma ApoE level
      reduced in AD patients (2.28 vs 3.78 MUg/mL, P < .001), and microRNA-1908 was up
      regulated in AD patients and was negatively associated with plasma ApoE (r = 
      0.32, P = .012). In human macrophage cell line THP-1 and astrocytoma cell line
      U87, microRNA-1908 could inhibit the mRNA and protein levels of ApoE by targeting
      its 3'untranslated region. Consistently, microRNA-1908 inhibits the ApoE-mediated
      Abeta clearance. CONCLUSIONS: Our study provides new insight into the mechanism
      of ApoE dysregulation in AD patients, and microRNA-1908 might be a therapeutic
      target for AD treatment.

PMID- 29635819
TI  - British Association of Urological Surgeons (BAUS) consensus document for the
      management of male genital emergencies - testicular trauma.
AB  - Male genital emergencies relating to the penis and scrotum are rare and require
      prompt investigation and surgical intervention. Clinicians are often unfamiliar
      with the management of these conditions and may not work in a specialist centre
      with on-site expertise in genitourethral surgery. A series of consensus
      statements have been developed by an expert consensus comprising British
      Association of Urological Surgeons (BAUS) Section of Andrology and Genitourethral
      Surgery together with experts from units throughout the UK. Testicular trauma
      requires prompt investigation and treatment in order to prevent the development
      of subfertility or hypogonadism. This series of consensus statements provide
      guidance for UK practice.

PMID- 29635820
TI  - Factors influencing nurses' intentions to leave adult critical care settings.
AB  - BACKGROUND: The shortage of critical care and specialist nurses has been an
      ongoing issue for many decades. Although all areas of nursing are affected,
      critical care areas are especially vulnerable to recruitment and retention
      problems. High nursing turnover in critical care areas is evident; however,
      research into the factors that influence nurses' intentions to leave adult
      critical care areas is limited. AIM: To explore factors that may influence
      nurses' intentions to leave adult critical care areas. OBJECTIVES: To appraise
      existing evidence and highlight gaps in knowledge regarding factors that may
      influence nurses' intentions to leave adult critical care areas. METHODS: A
      systematic mixed-method literature review was conducted. The search strategy was
      developed using the List, Keep and Delete approach, a framework used to identify
      search terms for systematic health care reviews. The following key words were
      used: intentions to leave, nurses, adult and critical care. The databases
      searched were BNI, CINAHL, PubMed, PsycINFO, Embase and Health B Elite from 2005
      to 2016. Primary data from non-critical care areas and neonatal and paediatric
      critical care areas were excluded. Comprehensive supplementary searching was
      performed. Papers were critically appraised using the NICE (2012) checklists.
      Data were analysed using the Braun and Clarke (2006) thematic framework. RESULTS:
      A total of 15 studies, including 13 cross-sectional studies and 2 qualitative
      studies, were reviewed. Three main themes emerged following data analysis. These
      themes were quality of the work environment, nature of working relationships and
      traumatic/stressful workplace experiences. CONCLUSIONS: The literature review
      highlighted the need for further research and greater understanding of how these
      themes may impact critical care nurses. Nurse managers and leaders should
      consider these findings when developing strategies to improve nurse retention.
      RELEVANCE TO PRACTICE: The shortage of critical care nurses is currently a global
      issue impacting costs and quality of patient care.

PMID- 29635822
TI  - The Ability to Deal With Difference: Turkish-Dutch Professionals as Go-Betweens
      in the Education Sector.
AB  - Based on sixteen semi-structured interviews, this article examines how second
      generation Turkish-Dutch education professionals experience their professional
      position in the ethnically homogeneous upper echelons of the Dutch education
      sector. The analysis shows that second-generation education professionals, being
      newcomers to higher-level positions in the sector, have to engage with diverse
      cultural repertoires at work. Instead of being stuck in-between these
      repertoires, second-generation education professionals actively "go-between"
      repertoires, employing their ability to deal with difference. In the increasingly
      super-diverse Dutch classrooms, this "go-between" attitude functions as a second
      generation advantage and is conceptually better suited than in-betweenness to
      describe the position of second-generation professionals.

PMID- 29635823
TI  - Occupational contact dermatitis caused by hydroxychloroquine sulfate.

PMID- 29635824
TI  - Psychometric properties of the "parental questionnaire: Enuresis/urinary
      incontinence" (PQ-EnU).
AB  - AIMS: The "Parental Questionnaire: Enuresis/Urinary Incontinence" (PQ-EnU) is
      widely-used in clinical assessment of nocturnal enuresis (NE) and daytime urinary
      incontinence (DUI). It includes 18 items regarding daytime (DW) and nighttime
      wetting (NW), 24 items concerning toilet habits (TH), and 14 items regarding
      behavioral problems (BP). The aim of the study was to evaluate reliability and
      validity of the PQ-EnU. METHODS: Parents of 490 children (M = 8.7 years [SD =
      2.9], 68.2% male) presented in an outpatient incontinence clinic completed the PQ
      EnU and the Child Behavior Checklist (CBCL). Internal consistencies, factorial
      structure, and convergent validity regarding incontinence diagnoses and
      psychopathology were examined. RESULTS: 84.1% had NE, 38.8% DUI, and 20.8% fecal
      incontinence (FI). Internal consistencies were good for TH and BP. A factor
      analysis of the TH scale revealed three subscales ("Lower urinary tract symptoms
      (LUTS)," "Bowel symptoms," and "Voiding dysfunctions"). The LUTS and "Bowel
      symptoms" subscales were significantly correlated to clinical diagnoses of DUI
      and FI, respectively. A factor analysis of the BP scale revealed also three
      subscales ("attention/school deficits," "impulsive-aggressive behavior" and
      "internalizing problems," which were all significantly correlated with the CBCL.
      The questionnaire discriminated significantly between children with and without
      DUI or FI, and children with and without a clinical CBCL score. CONCLUSIONS: The
      PQ-EnU is a valid and reliable parental questionnaire to measure incontinence,
      bladder/bowel symptoms, and behavioral problems in children. Due to its
      shortness, the PQ-EnU is an efficient measurement, which can be used in clinical
      settings and also as a screening tool for psychological symptoms.

PMID- 29635825
TI  - Influence of protein properties and protein modification on biodistribution and
      tumor uptake of anticancer antibodies, antibody derivatives, and non-Ig
      scaffolds.
AB  - Newly developed protein drugs that target tumor-associated antigens are often
      modified in order to increase their therapeutic effect, tumor exposure, and
      safety profile. During the development of protein drugs, molecular imaging is
      increasingly used to provide additional information on their in vivo behavior. As
      a result, there are increasing numbers of studies that demonstrate the effect of
      protein modification on whole body distribution and tumor uptake of protein
      drugs. However, much still remains unclear about how to interpret obtained
      biodistribution data correctly. Consequently, there is a need for more insight in
      the correct way of interpreting preclinical and clinical imaging data.
      Summarizing the knowledge gained to date may facilitate this interpretation. This
      review therefore provides an overview of specific protein properties and
      modifications that can affect biodistribution and tumor uptake of anticancer
      antibodies, antibody fragments, and nonimmunoglobulin scaffolds. Protein
      properties that are discussed in this review are molecular size, target
      interaction, FcRn binding, and charge. Protein modifications that are discussed
      are radiolabeling, fluorescent labeling drug conjugation, glycosylation,
      humanization, albumin binding, and polyethylene glycolation.

PMID- 29635826
TI  - Granulomatous tattoo reactions in permanent makeup of the eyebrows.

PMID- 29635827
TI  - Perfectionism and cognitive rigidity in anorexia nervosa: Is there an
      association?
AB  - Little is known about the relationship between neuropsychology, personality, and
      eating psychopathology in anorexia nervosa (AN). We aimed to investigate the
      interaction between set shifting and perfectionism in AN and to ascertain the
      role of perfectionism as a mediator between set shifting and eating
      psychopathology. Eighty-five patients with AN and 71 healthy controls completed
      Eating Disorder Inventory-2 (using 8 as a cut-off for generating groups with high
      vs. low perfectionism), Beck Depression Inventory, Wisconsin Card Sorting Test,
      Trail Making Task, and Hayling Sentence Completion Task. Our findings support
      heightened cognitive inflexibility in individuals with AN, particularly in those
      with high perfectionism. Perfectionism resulted to be a mediator of the
      relationship between a measure of set shifting and drive for thinness, but this
      finding did not remain significant when including in the model only those with
      AN. Taken together, these data suggest a complex and nonexclusive association
      between set shifting, eating psychopathology, and perfectionism.

PMID- 29635828
TI  - Maneuverability of Magnetic Nanomotors Inside Living Cells.
AB  - Spatiotemporally controlled active manipulation of external micro-/nanoprobes
      inside living cells can lead to development of innovative biomedical technologies
      and inspire fundamental studies of various biophysical phenomena. Examples
      include gene silencing applications, real-time mechanical mapping of the
      intracellular environment, studying cellular response to local stress, and many
      more. Here, for the first time, cellular internalization and subsequent
      intracellular manipulation of a system of helical nanomotors driven by small
      rotating magnetic fields with no adverse effect on the cellular viability are
      demonstrated. This remote method of fuelling and guidance limits the effect of
      mechanical transduction to cells containing external probes, in contrast to
      ultrasonically or chemically powered techniques that perturb the entire
      experimental volume. The investigation comprises three cell types, containing
      both cancerous and noncancerous types, and is aimed toward analyzing and
      engineering the motion of helical propellers through the crowded intracellular
      space. The studies provide evidence for the strong anisotropy, heterogeneity, and
      spatiotemporal variability of the cellular interior, and confirm the suitability
      of helical magnetic nanoprobes as a promising tool for future cellular
      investigations and applications.

PMID- 29635830
TI  - Trust and Society: Suggestions for Further Development of Niklas Luhmann's Theory
      of Trust.
AB  - This paper addresses an apparent gap in the work of Niklas Luhmann. While the
      issue of trust continues to receive widespread attention in the social sciences,
      Luhmann's interest in this topic declined following the development of his
      systems theory. It is argued that this decline does not reflect any diminished
      relevance of trust for systems theory, but rather that the architectural
      remodeling of theory cannot easily be applied to the issue of trust. Here, the
      issue of trust is reconceptualized as a connection medium. This entails a
      reconstruction of Luhmann's early theory of trust, especially with regard to
      function and social positioning. In this context, trust can in turn be linked to
      the concept of medium in Luhmann's late work. As a connection medium, trust
      mediates between the different levels of sociality-interaction, organization, and
      society. These theoretical considerations are employed to develop a more applied
      framework for empirical research, with a brief case study from southern Italy.
      From this perspective, the idea of trust as society's glue is seen to be overly
      simplistic. The common ethical understanding that more trust leads to a better
      society is also questioned on the grounds that social cooperation can also lead
      to social sclerosis. Finally, risk and trust are shown to accommodate the
      formation of different cultures of trust. The paper shows how Luhmann's updated
      version of trust can inspire current research and enhance our understanding of
      how trust operates in contemporary society.

PMID- 29635829
TI  - Percutaneous transapical approach and transcatheter closure for ventricular
      tachycardia ablation.

PMID- 29635831
TI  - Youth participation in 'post-secular' times: young Muslim and Buddhist
      practitioners as religious citizens.
AB  - Recently there has been renewed interest in the role of religion in the public
      sphere in the context of a 'post-secular' age characterized by the resurgence of
      religious identities and communities in increasingly diverse, multi-faith
      societies. Young people's active political and civic engagement has also emerged
      as a core challenge for robust democracies. While an interesting body of current
      research suggests that religious commitment may cultivate participation amongst
      youth by acting as an incubator of civic and political engagement, such
      literature often positions religiosity as outside of, and consequently at odds
      with participation in a secular public sphere. We suggest that while religiosity
      may indeed act as an incubator for civic and political engagement, we propose
      greater attention to an emergence of alternative, entwined conceptualizations of
      religious citizenship evident in the practices, performances and dispositions of
      young Muslim and Buddhist religious practitioners in Australia, whereby processes
      of individuation contribute to greater fluidity within and across the domains of
      the religious and the civic.

PMID- 29635832
TI  - Coping behavior in multiple sclerosis-complementary and alternative medicine: A
      cross-sectional study.
AB  - MAIN PROBLEM: Treatment options for multiple sclerosis (MS) have enlarged
      tremendously over the last years. Nonetheless, lots of patients look for
      alternative treatment options. The use of complementary and alternative medicine
      (CAM) is widespread in MS, however, its scientific investigation is limited so
      far. The aim of the study is to analyse clinical and demographical differences of
      MS patients in dependency of their CAM utilization as coping strategy. METHODS: A
      total of 254 patients with a clinically definite MS were examined in a
      semistructured interview. Additional standardized questionnaires were used to
      measure different aspects of coping with illness. All patients underwent
      neurological examination. RESULTS: About 206 of all enrolled patients are CAM
      users (81.1%). They have a longer disease duration (8.3 years vs 7.3 years, P =
      0.028) and show higher disability (median EDSS 4.0 vs 2.0, P < 0.001) than
      nonusers. CAM users differed significantly from nonusers in their coping behavior
      (P = 0.035). Users are brooding more heavily over the disease, looking for more
      information about MS, and are looking for a sense of their disease in religion
      more often than nonusers. CAM users are at a higher risk of depression. Almost
      two-thirds of CAM users (57.6%) reported positive effects on the well-being of
      their state of health. CONCLUSION: Coping behavior differs significantly between
      CAM users and nonusers. CAM utilization is associated with higher disability and
      depression. More than 80% of our cohort has used alternative or complementary
      methods. CAM utilization may mirror unmet needs in the treatment of MS.

PMID- 29635833
TI  - Seasonal variation in diet and nutrition of the northern-most population of
      Rhinopithecus roxellana.
AB  - There is a great deal of spatial and temporal variation in the availability and
      nutritional quality of foods eaten by animals, particularly in temperate regions
      where winter brings lengthy periods of leaf and fruit scarcity. We analyzed the
      availability, dietary composition, and macronutrients of the foods eaten by the
      northern-most golden snub-nosed monkey (Rhinopithecus roxellana) population in
      the Qinling Mountains, China to understand food choice in a highly seasonal
      environment dominated by deciduous trees. During the warm months between April
      and November, leaves are consumed in proportion to their availability, while
      during the leaf-scarce months between December and March, bark and leaf/flower
      buds comprise most of their diet. When leaves dominated their diet, golden snub
      nosed monkeys preferentially selected leaves with higher ratios of crude protein
      to acid detergent fiber. While when leaves were less available, bark and
      leaf/flower buds that were high in nonstructural carbohydrates and energy, and
      low in acid detergent fiber were selected. Southern populations of golden snub
      nosed monkey can turn to eating lichen, however, the population studied here in
      this lichen-absent area have adapted to their cool deciduous habitat by instead
      consuming buds and bark. Carbohydrate and energy rich foods appear to be the
      critical resources required for the persistence of this species in temperate
      habitat. The dietary flexibility of these monkeys, both among seasons and
      populations, likely contributes to their wide distribution over a range of
      habitats and environments.

PMID- 29635834
TI  - Bladder underactivity after prolonged stimulation of somatic afferent axons in
      the tibial nerve in cats.
AB  - AIMS: To establish an animal model of bladder underactivity induced by prolonged
      and intense stimulation of somatic afferent axons in the tibial nerve. METHODS:
      In seven cats under alpha-chloralose anesthesia, tibial nerve stimulation (TNS)
      of 30-min duration was repeatedly (3-8 times) applied at 4-6 times threshold (T)
      intensity for inducing a toe twitch to produce bladder underactivity determined
      by cystometry. Naloxone (1 mg/kg, i.v.) was administered to examine the role of
      opioid receptors in TNS-induced bladder underactivity. RESULTS: After prolonged
      (1.5-4 h) and intense (4-6T) TNS, a complete suppression of the micturition
      reflex occurred in six cats and an increase in bladder capacity to about 150% of
      control and a decrease in the micturition contraction amplitude to 50% of control
      occurred in one cat. The bladder underactivity was maintained for at least 1-1.5
      h. Naloxone reversed the bladder underactivity, but an additional 30-min TNS
      removed the naloxone effect. CONCLUSIONS: The results indicate that prolonged and
      intense activation of somatic afferent axons in the tibial nerve can suppress the
      central reflex mechanisms controlling micturition. This animal model may be
      useful for examining the pathophysiology of neurogenic bladder underactivity and
      for development of new treatments for underactive bladder symptoms.

PMID- 29635835
TI  - Biological signaling pathways and potential mathematical network representations:
      biological discovery through optimization.
AB  - Establishing the role that different genes play in the development of cancer is a
      daunting task. A step toward this end is the detection of genes that are
      important in the illness from high-throughput biological experiments.
      Furthermore, it is safe to say that it is highly unlikely that these show
      expression changes independently, even with a list of potentially important
      genes. A biological signaling pathway is a more plausible underlying mechanism as
      favored in the literature. This work attempts to build a mathematical network
      problem through the analysis of microarray experiments. A preselection of genes
      is carried out with a multiple criteria optimization framework previously
      published by our research group . Afterward, application of the Traveling
      Salesperson Problem and Minimum Spanning Tree network optimization models are
      proposed to identify potential signaling pathways via the most correlated path
      among the genes of interest. Biological evidencing is provided to assess the
      effectiveness of the proposed methods. The capability of our analysis strategy is
      also demonstrated through the undertaking of meta-analysis studies. Three
      important aspects are novel in this work: (1) our joint analyses of different
      groups of lung cancer states reveal new correlations, biologically evidenced, and
      previously undocumented; (2) computation of the correlation coefficients from
      expression differences leads to an effective use of network optimization methods;
      and (3) the methods yield mathematically optimal correlation structures: no other
      configuration is better correlated using the available information.

PMID- 29635837
TI  - Lethal fibrosing mediastinitis in a child possibly due to Mycobacterium
      tuberculosis.
AB  - Fibrosing mediastinitis (FM) is a rare benign disease resulting from an excessive
      fibro-inflammatory reaction in the mediastinum that can compress and occlude
      mediastinal structures. There is a granulomatous and a diffuse non-granulomatous
      form of FM. We present a case of granulomatous FM following possible tuberculosis
      in a young child who presented with severe compression of the airways, pulmonary
      artery and the superior vena cava (SVC), unresponsive to treatment, resulting in
      death. Bronchoscopic findings included concentric narrowing and mucosal
      hyperaemia of the tracheobronchial airways. This case raises awareness of this
      rare complication and the limited treatment options available.

PMID- 29635836
TI  - Attitudes and intentions of Greek teachers towards teaching pupils with dyslexia:
      An application of the theory of planned behaviour.
AB  - The present study aims to examine Greek public primary school teachers' attitudes
      and intention towards teaching pupils with dyslexia using a model of the theory
      of planned behaviour (TPB). Toward that aim, 304 teachers aged between 22 and 59
      years old, with an average overall work experience of 16.6 years completed a TPB
      questionnaire which assessed their attitudes, subjective norms and perceived
      behavioural control, their intention, as well as other exogenous factors. The
      validity and the reliability of the questionnaire were found to be adequate.
      Overall, the participating teachers report a wide range of educational
      interventions for pupils with dyslexia emphasizing the psychological aspects of
      support. They also face a number of barriers, but in general they express neutral
      to positive attitudes to dyslexia. Results show that attitudes, subjective norms
      and perceived behavioural control significantly predicted the teachers' intention
      towards teaching dyslexic pupils, thus confirming the applicability of the
      selected TPB model. Recommendations for teachers' training and limitations of the
      study are discussed.

PMID- 29635838
TI  - Interventions in children with renovascular hypertension: A 27-year retrospective
      single-center experience.
AB  - BACKGROUND: Renovascular hypertension (RVH) can be caused by renal artery
      stenosis (RAS) and/or middle aortic syndrome (MAS). METHODS: Patients who
      received surgical or transcatheter treatment for RVH between 1/1991 and 11/2017
      were retrospectively reviewed using age = adjusted blood pressure ratio (BPR).
      RESULTS: Fifty-three patients diagnosed with RVH at a median age of 4.5 (0-18)
      years were included. Vascular involvement ranged from MAS with RAS (20), RAS only
      (32), and MAS only (1). The first intervention was transcatheter in 47 patients
      (transcatheter group: angioplasty = 41, stenting = 5, and thrombectomy = 1), and
      surgical in 6 patients (surgical group), occurring at a median age of 6.2 (0.1
      19.6) years. There was a change toward transcatheter interventions as the first
      procedure over the study period. First reinterventions in the transcatheter group
      (27 lesions in 18 patients) were repeat transcatheter (in 20 lesions) and surgery
      (7 lesions) at a median of 92 (2-2555) days; in the surgical group (5 lesions in
      4 patients) first reinterventions were transcatheter (4 lesions) and repeat
      surgery (1) at a median of 2.2 (1.1-12.0) years. A total of 136 transcatheter and
      30 surgical discrete interventions were performed. There was a significant
      decline in antihypertensive medications and BPR at 4-6 months after the first
      intervention and on last follow-up in patients initially treated by transcatheter
      means while the decline was not significant in the surgical group (limited by
      small sample size). Complications were significantly more common in the surgical
      group (P < .01), 11/27 (41%) vs 10/136 (7.4%). Four patients died (2 from each
      group): 2 with congenital renal artery atresia and MAS, 2 with MAS and RAS. The
      median follow-up interval was 3.6 (0.1-35.2) years. CONCLUSION: Pediatric
      patients with RVH treated with transcatheter means as the first intervention had
      significant improvement in BPR, as well as decline in antihypertensive
      medications and were less likely to suffer major complications.

PMID- 29635839
TI  - Mental load during cognitive performance in complex regional pain syndrome I.
AB  - BACKGROUND: Complex regional pain syndrome (CRPS) is associated with deficits in
      limb recognition. The purpose of our study was to determine whether mental load
      during this task affected performance, sympathetic nervous system activity or
      pain in CRPS patients. METHODS: We investigated twenty CRPS-I patients with pain
      in the upper extremity and twenty age- and sex-matched healthy controls. Each
      participant completed a limb recognition task. To experimentally manipulate
      mental load, the presentation time for each picture varied from 2 s (greatest
      mental load), 4, 6 to 10 s (least mental load). Before and after each run, pain
      intensity was assessed. Skin conductance was recorded continuously. RESULTS:
      Patients with CRPS did not differ from controls in terms of limb recognition and
      skin conductance reactivity. However, patients with CRPS reported an increase in
      pain during the task, particularly during high mental load and during the latter
      stages of the task. Interestingly, state anxiety and depressive symptoms were
      also associated with increases in pain intensity during high mental load.
      CONCLUSIONS: These findings indicate that high mental load intensifies pain in
      CRPS. The increase of pain in association with anxiety and depression indicates a
      detrimental effect of negative affective states in situations of high stress and
      mental load in CRPS. SIGNIFICANCE: The effects of mental load need to be
      considered when patients with CRPS-I are investigated for diagnostic or
      therapeutic reasons.

PMID- 29635840
TI  - Of Babies and Bath Water.

PMID- 29635841
TI  - Occupational contact dermatitis caused by polyurethane foam: 6 cases.

PMID- 29635842
TI  - A randomised controlled trial of the clinical effectiveness of multi-layer
      silicone foam dressings for the prevention of pressure injuries in high-risk aged
      care residents: The Border III Trial.
AB  - Pressure injuries are prevalent in highly dependent aged care residents. This
      study investigated the clinical effectiveness of the application of the Mepilex
      Border Sacrum and Mepilex Heel dressings to prevent the development of facility
      acquired pressure injuries. A total of 288 recently admitted residents were
      enrolled from 40 Australian nursing homes into a randomised controlled trial.
      Residents randomised to standard care (n = 150) received pressure injury
      prevention as recommended by international guidelines. Residents randomised to
      the intervention (n = 138) received standard pressure injury prevention care and
      had dressings applied to their sacrum and heels. Participants were comparable on
      demographic and physiological parameters. More residents in the control group
      developed pressure injuries than in the intervention group (16 vs 3, P = 0.004),
      and they developed more pressure injuries in total than residents in the
      intervention group. The results represent a relative risk reduction of 80% for
      residents treated with the dressings and for every 12 patients that we treated we
      prevented one pressure injury. Based on our findings, we conclude that the use of
      the Molnlycke Mepilex Border Sacrum and Mepilex Heel dressings confers a
      significant additional protective benefit to nursing home residents with a high
      risk of developing a facility-acquired pressure injury.

PMID- 29635843
TI  - Therapeutic prospects of targeting myeloid-derived suppressor cells and immune
      checkpoints in cancer.
AB  - Immune evasion is a characteristic of most human malignancies and is induced via
      various mechanisms. Immunosuppressive cells, including myeloid-derived suppressor
      cells (MDSC) and regulatory T cells (Treg), are key mediators in assisting tumors
      to escape immune surveillance. Expansion of MDSC, Treg and elevated levels of
      immune checkpoints (IC) are frequently detected in the tumor microenvironment and
      periphery of cancer patients. Various therapeutic agents have been shown to
      target MDSC and to block IC for inducing anti-tumor immunity and reversal of
      tumor immune escape. Importantly, some recent studies have shown that MDSC
      targeting improves the efficacy of IC blockade in cancer therapy. However, there
      is a pressing need to improve our understanding of the distinct role of these
      cells to develop combination therapy that attacks tumor cells from all frontiers
      to improve cancer therapeutics. Herein, we discuss the role of MDSC in cancer
      progression, interactions with IC in the context of anti-cancer immunity and the
      current therapeutic strategies to target MDSC and block IC in cancer.

PMID- 29635844
TI  - Children with severe acute asthma admitted to Dutch PICUs: A changing landscape.
AB  - : The number of children requiring pediatric intensive care unit (PICU) admission
      for severe acute asthma (SAA) around the world has increased. OBJECTIVES: We
      investigated whether this trend in SAA PICU admissions is present in the
      Netherlands. METHODS: A multicenter retrospective cohort study across all
      tertiary care PICUs in the Netherlands. Inclusion criteria were children (2-18
      years) hospitalized for SAA between 2003 and 2013. Data included demographic
      data, asthma diagnosis, treatment, and mortality. RESULTS: In the 11-year study
      period 590 children (660 admissions) were admitted to a PICU with a threefold
      increase in the number of admissions per year over time. The severity of SAA
      seemed unchanged, based on the first blood gas, length of stay and mortality rate
      (0.6%). More children received highflow nasal cannula (P < 0.001) and fewer
      children needed invasive ventilation (P < 0.001). In 58% of the patients the
      maximal intravenous (IV) salbutamol infusion rate during PICU admission was 1
      mcg/kg/min. However, the number of patients treated with IV salbutamol in the
      referring hospitals increased significantly over time (P = 0.005). The proportion
      of steroid-naive patients increased from 35% to 54% (P = 0.004), with a
      significant increase in both age groups (2-4 years [P = 0.026] and 5-17 years [P
      = 0.036]). CONCLUSIONS: The number of children requiring PICU admission for SAA
      in the Netherlands has increased. We speculate that this threefold increase is
      explained by an increasing number of steroid-naive children, in conjunction with
      a lowered threshold for PICU admission, possibly caused by earlier use of
      salbutamol IV in the referring hospitals.

PMID- 29635845
TI  - Chitosan nanoparticles-loaded Citrus aurantium essential oil: a novel delivery
      system for preserving the postharvest quality of Agaricus bisporus.
AB  - BACKGROUND: One of the main problems in the button mushroom industry is the rapid
      deterioration of fruit bodies after harvest. Today, nanotechnology has become a
      more reliable technique to improve the quality of products in food packaging. In
      the present study, the effectiveness of chitosan nanoparticles containing Citrus
      aurantium essential oil on postharvest quality of white button mushroom was
      examined and compared to essential oil fumigation and control treatments.
      RESULTS: Based on high-resolution transmission electron microscopy and dynamic
      light scattering, nanoparticles exhibited a spherical shape of 20-60 nm diameter.
      The results revealed that the application of chitosan nanoparticles loaded with
      C. aurantium oil significantly decelerated the rate of color change, weight loss
      and firmness compared to fumigation with essential oil and control treatments.
      Treatment of fruit bodies with chitosan nanoparticles loaded with C. aurantium
      oil promoted the accumulation of phenolic compounds and ascorbic acid, and
      resulted in increases in catalase and superoxide dismutase and a decrease in
      polyphenol oxidase activities, as the highest antioxidant capacity was observed
      after 15 days of cold storage. CONCLUSION: This present research demonstrates
      that gradual release of C. aurantium essential oil from chitosan nanoparticles
      could be an effective and practical method for extending the shelf life of white
      button mushroom up to 15 days without significant decrease in antioxidant
      capacity. (c) 2018 Society of Chemical Industry.

PMID- 29635846
TI  - Primary lymphomatoid granulomatosis in the central nervous system: A report of
      three cases.
AB  - Lymphomatoid granulomatosis (LYG) is a rare lymphoproliferative disorder
      characterized by infiltration of Epstein-Barr virus (EBV)-positive large atypical
      B-cells in an angiocentric fashion in a mixed inflammatory background. The
      histologic spectrum of LYG ranges from reactive proliferation to diffuse large B
      cell lymphoma according to the number of EBV+ B-cells. It is known that virtually
      all patients have pulmonary involvement, whereas primary LYG of the other organs
      has been rarely reported. Herein, we describe three cases of primary LYG of the
      central nervous system (CNS) without pulmonary lesions, and this is the first
      collection to be reported in Korea. All of the cases revealed multifocal
      enhancing necrotic brain lesions masking as metastatic tumors, infection or
      vasculitis. These patients were successfully managed by corticosteroids and
      immunomodulating agents without chemotherapy against malignant lymphoma even in
      grade 3 LYG. We assume that primary CNS LYG might be less aggressive and more
      controllable than pulmonary LYG. The clinicopathologic characteristics of the
      cases with a special regard to the differential diagnosis and clinical courses
      are discussed in combination with an overview of the literature.

PMID- 29635847
TI  - A Q-methodology study among caregivers of people with moderate intellectual
      disabilities on their clients' health care: An example in oral health.
AB  - BACKGROUND: People with intellectual disabilities have less favourable outcomes
      in-among others-oral health variables, compared to their peers without
      intellectual disabilities. Before being able to develop target interventions for
      caregivers, all their prevailing viewpoints regarding oral hygiene need to be
      identified. METHODS: This Q-methodology study-conducted among 40 caregivers of
      care-dependent Institutionalized living persons with moderate intellectual
      disability-used by-person factor analysis to reveal clusters of caregivers based
      on the way their statements were sorted. RESULTS: A 4-factor solution was chosen
      based on both the Q-sorting and the interviews. The four factors identified were
      responsible and perseverant, motivated but aware of obstacles, social minded and
      knowledgeable and concerned and insecure. CONCLUSION: Q-methodology can be used
      to determine the different attitudes that caregivers have regarding oral health
      care. Developing a tool to determine into which factor caregivers should be
      categorized may be the next step in tailoring oral health instruction.

PMID- 29635848
TI  - Quorum-dependent transfer of the opine-catabolic plasmid pAoF64/95 is regulated
      by a novel mechanism involving inhibition of the TraR antiactivator TraM.
AB  - We previously described a plasmid of Agrobacterium spp., pAoF64/95, in which the
      quorum-sensing system that controls conjugative transfer is induced by the opine
      mannopine. We also showed that the quorum-sensing regulators TraR, TraM, and TraI
      function similarly to their counterparts in other repABC plasmids. However, traR,
      unlike its counterpart on Ti plasmids, is monocistronic and not located in an
      operon that is inducible by the conjugative opine. Here, we report that both traR
      and traM are expressed constitutively and not regulated by growth with mannopine.
      We report two additional regulatory genes, mrtR and tmsP, that are involved in a
      novel mechanism of control of TraR activity. Both genes are located in the
      distantly linked region of pAoF64/95 encoding mannopine utilization. MrtR, in the
      absence of mannopine, represses the four-gene mocC operon as well as tmsP, which
      is the distal gene of the eight-gene motA operon. As judged by a bacterial two
      hybrid analysis, TmsP, which shows amino acid sequence relatedness with the TraM
      binding domain of TraR, interacts with the antiactivator. We propose a model in
      which mannopine, acting through the repressor MrtR, induces expression of TmsP
      which then titrates the levels of TraM thereby freeing TraR to activate the tra
      regulon.

PMID- 29635849
TI  - The impact of weather, road surface, time-of-day, and light conditions on
      severity of bicycle-motor vehicle crash injuries.
AB  - BACKGROUND: This study examined whether environmental variables including
      weather, road surface, time-of-day, and light conditions were associated with the
      severity of injuries resulting from bicycle-motor vehicle crashes. METHODS: Using
      log-binomial regressions, we analyzed 113 470 police reports collected between
      2000 and 2014 in four U.S. states with environmental and injury severity
      information. "Severe" injuries included fatal and incapacitating injuries, and
      "non-severe" included non-incapacitating, possible or no-injuries. RESULTS: Light
      condition was significantly associated with the injury severity to the bicyclist
      with more severe injuries at dawn (RR = 1.62 [95%CI 1.35-1.94]) and during
      darkness (both lighted and unlighted roads: 1.32 [1.24-1.40], respectively, 1.57
      [1.41-1.76]) as compared to daylight. In these conditions of low visibility, risk
      was further increased during early morning hours before 7 am (1.61 [1.22-2.13]).
      CONCLUSIONS: Crashes in low light conditions and during early morning hours are
      more likely to result in higher injury severity.

PMID- 29635850
TI  - Phototunable Dielectric Huygens' Metasurfaces.
AB  - Conventional dielectric metasurfaces achieve their properties through geometrical
      tuning and consequently are static. Although some unique properties are
      demonstrated, the usefulness for realistic applications is thus inherently
      limited. Here, control of the resonant eigenmodes supported by Huygens'
      metasurface (HMS) absorbers through optical excitation is proposed and
      demonstrated. An intensity transmission modulation depth of 99.93% is
      demonstrated at 1.03 THz, with an associated phase change of greater than pi/2
      rad. Coupled mode theory and S-parameter simulations are used to elucidate the
      mechanism underlying the dynamics of the metasurface and it is found that the
      tuning is primarily governed by modification of the magnetic dipole-like odd
      eigenmode, which both lifts the degeneracy, and eliminates critical coupling. The
      dynamic HMS demonstrates wide tunability and versatility which is not limited to
      the spectral range demonstrated, offering a new path for reconfigurable
      metasurface applications.

PMID- 29635851
TI  - Brain PET substrate of impulse control disorders in Parkinson's disease: A
      metabolic connectivity study.
AB  - Impulse control disorders (ICDs) have received increased attention in Parkinson's
      disease (PD) because of potentially dramatic consequences. Their physiopathology,
      however, remains incompletely understood. An overstimulation of the
      mesocorticolimbic system has been reported, while a larger network has recently
      been suggested. The aim of this study is to specifically describe the metabolic
      PET substrate and related connectivity changes in PD patients with ICDs. Eighteen
      PD patients with ICDs and 18 PD patients without ICDs were evaluated using
      cerebral 18F-fluorodeoxyglucose positron emission tomography. SPM-T maps
      comparisons were performed between groups and metabolic connectivity was
      evaluated by interregional correlation analysis (IRCA; p < .005, uncorrected; k >
      130) and by graph theory (p < .05). PD patients with ICDs had relative increased
      metabolism in the right middle and inferior temporal gyri compared to those
      without ICDs. The connectivity of this area was increased mostly with the
      mesocorticolimbic system, positively with the orbitofrontal region, and
      negatively with both the right parahippocampus and the left caudate (IRCA).
      Moreover, the betweenness centrality of this area with the mesocorticolimbic
      system was lost in patients with ICDs (graph analysis). ICDs are associated in PD
      with the dysfunction of a network exceeding the mesocorticolimbic system, and
      especially the caudate, the parahippocampus, and the orbitofrontal cortex,
      remotely including the right middle and inferior temporal gyri. This latest area
      loses its central place with the mesocorticolimbic system through a connectivity
      dysregulation.

PMID- 29635852
TI  - Intracranial haemorrhage in children with inherited bleeding disorders in the UK
      2003-2015: A national cohort study.
AB  - INTRODUCTION: Intracranial haemorrhage in children with inherited bleeding
      disorders is a potentially life-threatening complication and presents a
      significant therapeutic challenge. AIM: To define the characteristics, management
      and outcomes of intracranial haemorrhage presenting in UK children <=16 years of
      age with inherited bleeding disorders from 2003 to 2015. METHOD: Retrospective
      analysis of children treated at UK haemophilia centres. RESULTS: Of 66 children
      presenting with Intracranial haemorrhage (ICH), 82% had haemophilia A or B, 3%
      VWD and 15% a rare IBD. The IBD was a severe phenotype in 91%. The rates of ICH
      were 6.4 and 4.2 per 1000 patient years for haemophilia A and B, respectively.
      Median age at presentation was 4 months (33% neonates; 91% children <2 years of
      age). In neonates, delivery was spontaneous vaginal (SV) in 11, instrumental in
      6, caesarean in 4 and unknown in 1. In children with haemophilia, the risk of ICH
      after instrumental delivery was 10.6 times greater than after SV delivery. Trauma
      was more common in children >2 years (67%) than in children 1 month to 2 years
      (18%; P = .027). Prior to ICH, only 4.5% of children were on prophylaxis. 6% of
      haemophiliacs had an inhibitor. The median duration of initial replacement
      therapy was 15 days. Mortality was 13.5%. Neurological sequelae occurred in 39%
      of survivors, being more common following intracerebral bleeding. In haemophilia
      survivors, 52% subsequently developed a FVIII inhibitor. CONCLUSION: Intracranial
      haemorrhage occurs most frequently in children with severe IBDs, during the first
      2 years of life and in children not receiving prophylaxis. Intracranial
      haemorrhage often occurs without documented trauma.

PMID- 29635853
TI  - Allergic contact dermatitis caused by isobornyl acrylate in OmniPod, an
      innovative tubeless insulin pump.
AB  - BACKGROUND: The frequency of allergic contact dermatitis caused by
      (meth)acrylates is increasing worldwide, and isobornyl acrylate (IBOA) has been
      identified as a culprit sensitizer in FreeStyle Libre, a medical device used by
      diabetic patients. OBJECTIVES: To report on 4 patients sensitized to IBOA
      contained in OmniPod, a new, tubeless insulin pump, and to describe the clinical
      and chemical analytical work-up. METHOD: Four patients with eczematous skin
      eruptions after using OmniPod, including 2 with previous adverse skin reactions
      to FreeStyle Libre, were patch tested with a baseline series and additional
      (meth)acrylates, including IBOA in several concentrations and/or vehicles. Gas
      chromatography-mass spectrometry (GC-MS) was used to identify the presence of
      IBOA in OmniPod. RESULTS: All patients were shown to be sensitized to IBOA. GC-MS
      identified IBOA in OmniPod, with the highest concentrations being found in the
      unit itself and not in the adhesive patch. CONCLUSIONS: The OmniPod tubeless
      insulin pump is another source of IBOA, and its use may lead to primary
      sensitization to this acrylate, or may provoke elicitation of allergic contact
      dermatitis in previously sensitized patients. Our cases highlight the need to
      obtain satisfactory cooperation from pharmaceutical companies involved in the
      manufacture of these widely used medical devices.

PMID- 29635854
TI  - Urea plus nitrate pretreatment of rice and wheat straws enhances degradation and
      reduces methane production in in vitro ruminal culture.
AB  - BACKGROUND: Urea pretreatment of straw damages fiber structure, while nitrate
      supplementation of ruminal diets inhibits enteric methane production. The study
      examined the combined effects of these treatments on ruminal substrate
      biodegradation and methane production using an in vitro incubation system. Rice
      and wheat straws were pretreated with urea (40 g kg-1 straw dry matter, DM) and
      urea + ammonium nitrate (34 + 6 g kg-1 dry matter (DM), respectively), and each
      straw (control, urea, urea+nitrate) was used in batch culture incubations in
      three replications (runs). RESULTS: Urea pretreatment increased (P < 0.05)
      neutral-detergent solubles (NDS) content (+17%) and in vitro DM degradation of
      rice straw, in comparison with control. Urea+nitrate pretreatment of rice and
      wheat straws had higher (P < 0.05) NDS content, in vitro DM degradation and
      propionate molar proportion, and lower (P < 0.05) acetate:propionate ratio and
      lower methane production with a decline of methanogens, in comparison to control.
      CONCLUSIONS: Urea+nitrate pretreatment combines positive effects of urea
      pretreatment and nitrate supplementation, and can be a potential strategy to
      improve ruminal biodegradation, facilitate propionate production and reduce
      methane production from lignified straws. (c) 2018 Society of Chemical Industry.

PMID- 29635855
TI  - Identification and description of controlled clinical trials in Spanish language
      dental journals.
AB  - BACKGROUND: To identify controlled clinical trials (CCTs) published in Spanish
      and in Latin American dental journals, and provide access to this body of
      evidence in a single source. METHODS: Handsearching, following Cochrane
      Collaboration guidelines, of CCTs published in Spanish dental journals from Spain
      and Latin America. For each eligible trial, we collected the dental specialty,
      the interventions evaluated, whether and how randomisation was achieved, and the
      corresponding bibliographic reference. RESULTS: We handsearched 107 journals
      published in Spain and Latin America in Spanish. Over 17 051 articles, 244
      (1.43%) were CCTs. These studies focused mainly on periodontics (70, 29.0%) and
      oral and maxillofacial surgery (66, 27.0%), assessing mostly pharmacological
      interventions (112, 46.0%). One hundred fifty-three studies (62.7%) used a random
      allocation of participants to study arms. CONCLUSIONS: A significant number of
      dental journals published in Spain and Latin America in Spanish language present
      original research relevant to inform clinical practice. These journals are not
      indexed in the major electronic databases. PRACTICAL IMPLICATIONS: References to
      the identified CCTs are now available in CENTRAL, the Cochrane Collaboration
      repository for these studies. We call for adherence to the CONSORT statement in
      dentistry to improve reporting of CCTs in journals published in Spanish language.

PMID- 29635856
TI  - Impact of Medicare Advantage penetration and hospital competition on technical
      efficiency of nursing care in US intensive care units.
AB  - This study aimed to evaluate technical efficiency of US intensive care units and
      determine the effects of environmental factors on technical efficiency in
      providing quality of nursing care. Data were obtained from the 2014 National
      Database of Nursing Quality Indicators and the Centers for Medicare and Medicaid
      Services. Data envelopment analysis was used to estimate technical efficiency for
      each intensive care unit. Multilevel modeling was used to determine the effects
      of environmental factors on technical efficiency. Overall, Medicare Advantage
      penetration and hospital competition in a market did not create pressure for
      intensive care units to become more efficient by reducing their inputs. However,
      these 2 environmental factors showed positive influences on technical efficiency
      in intensive care units with certain levels of technical efficiency. The
      implications of the study results for management strategies and health policy may
      vary according to the levels of technical efficiency in intensive care units.
      Further studies are needed to examine why and how intensive care units with
      particular levels of technical efficiency are differently affected by certain
      environmental factors.

PMID- 29635857
TI  - Effect profile of paracetamol, Delta9-THC and promethazine using an evoked pain
      test battery in healthy subjects.
AB  - BACKGROUND: A battery of evoked pain tasks (PainCart) was developed to
      investigate the pharmacodynamic properties of novel analgesics in early-phase
      clinical research. As part of its clinical validation, compounds with different
      pharmacological mechanisms of actions are investigated. The aim was to
      investigate the analgesic effects of classic and nonclassic analgesics compared
      to a sedating negative control in a randomized placebo-controlled crossover study
      in 24 healthy volunteers using the PainCart. METHODS: The PainCart consisted of
      pain tasks eliciting electrical, pressure, heat, cold and inflammatory pain.
      Subjective scales for cognitive functioning and psychotomimetic effects were
      included. Subjects were administered each of the following oral treatments:
      paracetamol (1000 mg), Delta9-THC (10 mg), promethazine (50 mg) or matching
      placebo. Pharmacodynamic measurements were performed at baseline and repeated up
      to 10 h postdose. RESULTS: Paracetamol did not show a significant reduction in
      pain sensation or subjective cognitive functioning compared to placebo.
      Promethazine induced a statistically significant reduction in PTT for cold
      pressor and pressure stimulation. Furthermore, reduced subjective alertness was
      observed. Delta9-THC showed a statistically significant decrease in PTT for
      electrical and pressure stimulation. Delta9-THC also demonstrated subjective
      effects, including changes in alertness and calmness, as well as feeling high and
      psychotomimetic effects. CONCLUSIONS: This study found a decreased pain tolerance
      due to Delta9-THC and promethazine, or lack thereof, using an evoked pain task
      battery. Pain thresholds following paracetamol administration remained unchanged,
      which may be due to insufficient statistical power. We showed that pain
      thresholds determined using this pain test battery are not driven by sedation.
      SIGNIFICANCE: The multimodal battery of evoked pain tasks utilized in this study
      may play an important role in early-phase clinical drug development. This battery
      of pain tasks is not sensitive to the effects of sedation alone, and thus
      suitable to investigate the analgesic potential of novel analgesic compounds.

PMID- 29635858
TI  - Propagation of Enzyme-Induced Surface Events inside Polymer Nanoassemblies for a
      Fast and Tunable Response.
AB  - We report a new molecular design strategy that allows for the propagation of
      surface enzymatic events inside a supramolecular assembly for accelerated
      molecular release. The approach addresses a key shortcoming encountered with many
      of the currently available enzyme-induced disassembly strategies, which rely on
      the unimer-aggregate equilibria of amphiphilic assemblies. The enzymatic response
      of the host to predictably tune the kinetics of guest-molecule release can be
      programmed by controlling substrate accessibility through electrostatic
      complexation with a complementary polymer. Accelerated guest release in response
      to the enzyme is shown to be accomplished by a cooperative mechanism of enzyme
      triggered supramolecular host disassembly and host reorganization.

PMID- 29635859
TI  - Disturbance from traditional fire management in subalpine heathlands increases
      Afro-alpine plant resilience to climate change.
AB  - Species are often controlled by biotic factors such as competition at the warm
      edge of their distribution range. Disturbances at the treeline, disrupting
      competitive dominance, may thus enable alpine species to utilize lower altitudes.
      We searched for evidence for range expansion in grazed, fire-managed Ethiopian
      subalpine Erica heathlands across a 25-year chronosequence. We examined vascular
      plant composition in 48 plots (5 * 5 m) across an altitudinal range of 3,465
      3,711 m.a.s.l. and analyzed how community composition changed in relation to
      increasing competition over time (using a Shade index based on Erica shrub height
      and cover) and altitude. Species' habitats and altitudinal ranges were derived
      from literature. Time since fire explained more variation (r2  = .41) in species
      composition than altitude did (r2  = .32) in an NMDS analysis. Community-weighted
      altitudinal optima for species in a plot decreased strongly with increasing shade
      (GLM, Standardized Regression Coefficient SRC = -.41, p = .003), but increased
      only weakly with altitude (SRC = .26, p = .054). In other words, young stands
      were dominated by species with higher altitudinal optima than old stands. Forest
      species richness increased with Log Shade index (SRC = .12, p = .008), but was
      unaffected by altitude (SRC = -.07, p = .13). However, richness of alpine and
      heathland species was not highest in plots with lowest Shade index, but displayed
      a unimodal pattern with an initial increase, followed by a decrease when shading
      increased (altitude was not significant). Our results indicate that disturbance
      from the traditional patch burning increases the available habitat for less
      competitive high-altitude plants and prevents tree line ascent. Therefore,
      maintaining, but regulating, the traditional land use increases the Afro-alpine
      flora's resilience to global warming. However, this system is threatened by a new
      REDD+ program attempting to increase carbon storage via fire suppression. This
      study highlights the importance of understanding traditional management regimes
      for biodiversity conservation in cultural landscapes in an era of global change.

PMID- 29635860
TI  - Social and ecological correlates of space use patterns in Bwindi mountain
      gorillas.
AB  - Space use patterns determine access to resources necessary for survival and
      reproduction. Although it is recognized that the interplay between social and
      ecological variables shapes spacing patterns, few studies in group-living animals
      have simultaneously assessed their importance in a comprehensive approach using
      different spatiotemporal space use measures. In territorial species, such
      patterns are strongly determined by between-group competition, but its impact in
      non-territorial species is poorly understood. To better understand the role of
      social and ecological variables in non-territorial mountain gorillas (Gorilla
      beringei beringei), we simultaneously evaluated the impact of between-group
      competition (local gorilla population density and frequency of intergroup
      encounters) and within-group competition (group size) on space use patterns in 13
      gorilla groups in Bwindi Impenetrable National Park, Uganda, while also examining
      variation in food availability (herbaceous food availability and level of
      frugivory). We found evidence of between-group competition, indicated by a
      decline of both monthly home range size and frequency of revisits to each part of
      the home range as the local gorilla population density increased and by an
      increase in daily travel distance on days when intergroup encounters occurred.
      Within-group feeding competition was inferred by a decrease in the frequency of
      revisits as group size increased. Lastly, food availability influenced the
      gorillas' spacing patterns, as indicated by a decline in monthly home range size
      as herbaceous food availability increased and by an increase in daily travel
      distance as the degree of frugivory increased. In sum, our results suggest that
      Bwindi gorillas adapted their space use according to the constraints of
      intraspecific competition and the availability of food resources. We provide some
      of the first evidence of between-group competition influencing spacing patterns
      in a non-territorial species. This study suggests a gradient between
      territoriality and non-territoriality, along which the level of between-group
      competition varies.

PMID- 29635861
TI  - Identification of novel antilipogenic agents targeting fatty acid biosynthesis
      through structure-based virtual screening.
AB  - An Asinex Gold Platinium chemical library subset of 12 055 compounds was screened
      employing docking simulations in the active site of the human FAS KS domain.
      Among them, 13 compounds were further evaluated for their ability to inhibit
      fatty acid biosynthesis. Four compounds were found to be active in particular
      ASN05064661 and ASN05374526 with IC50 values of 6.6 and 10.5 MUm, respectively. A
      binding mode study was further conducted with these two compounds structurally
      related to benzene sulfonamide and aromatic polyamide. This study showed that
      they fit tightly with the active site with several interactions, notably with the
      key residues Cys161, His293, and His331.

PMID- 29635862
TI  - A functional haplotype of NFKB1 influence susceptibility to oral cancer: a
      population-based and in vitro study.
AB  - Genetic variations of NF-kappaB and its inhibitor IkappaB genes and their
      biological mechanism in oral cancer were not well recognized. The purpose of this
      study was to evaluate the associations of polymorphisms in NFKB1 and NFKBIA with
      oral cancer susceptibility, and further explore their potential mechanism in
      vitro. First, the polymorphisms of NFKB1 and NFKBIA were genotyped through iPLEX
      Sequenom MassARRAY platform in a case-control study with 425 oral cancer patients
      and 485 healthy controls. Then, the function was explored by a luciferase
      reporter assay and an electrophoretic mobility shift assay (EMSA) in human tongue
      squamous cell carcinoma cell lines. The results indicated that NFKB1 rs28362491
      Del/Del and rs72696119 G/G genotypes were associated with the risk of oral
      cancer, with a strong linkage disequilibrium (D' = 0.991, r2  = 0.971). Moreover,
      DG haplotype of NFKB1 also showed a significant increased risk (OR = 1.25, 95%
      CI: 1.02-1.53, P = 0.030). Dual-luciferase reporter assays further revealed that
      the plasmids with DG or IG or DC haplotype transfected with Tca-8113 cells or CAL
      27 cells had a lower luciferase expression than that with IC haplotype. EMSA
      demonstrated that 4-bp ATTG deletion in the promoter of NFKB1 abolished the
      binding site of transcription factor. Our preliminary findings suggest that the
      haplotype of rs28362491 and rs72696119 in NFKB1 could act as a novel genetic
      marker to predict oral cancer risk in the southeast of China, but much more
      extensive researches still need to be conducted.

PMID- 29635864
TI  - Using efficacy cues in persuasive health communication is more effective than
      employing threats - An experimental study of a vaccination intervention against
      Ebola.
AB  - OBJECTIVES: Although much effort has been made to study fear appeals in
      persuasive health communication, there is still mixed support for the
      effectiveness of this approach. Therefore, this research investigated the effect
      of invoked fear via health communication messages on crucial components of the
      Extended Parallel Process Model (EPPM) by focusing on the rarely examined
      interaction between perceptions of threat and efficacy and their effects on fear
      control and danger control processes as well as health-relevant outcomes. DESIGN:
      We recruited 447 participants (Mage  = 32.00 years; 64% female) for a 2 * 2
      between-subjects experimental study via quota sampling. While completing an
      online questionnaire, subjects were randomly assigned to view one of four
      versions of a mock website containing information about vaccinations against
      Ebola virus disease (EVD), which varied in threat and efficacy. METHODS: After
      seeing the stimulus, participants completed assessments of their perceptions of
      threat and efficacy, evoked fear, adaptive and defensive responses to the
      presented message, attitudes, and intentions. Structure equation modelling (SEM)
      was used to analyse the relationships within the model (EPPM). RESULTS: Promoting
      efficacy with respect to EVD was more effective than emphasizing threat,
      resulting in danger control rather than fear control processes. Although threat
      may be effective in attracting peoples' attention, there is a comparatively small
      effect of evoked fear on attitudes and intentions. CONCLUSIONS: The data support
      the assumption that there is an important association between threat and coping
      appraisals facilitating behaviour change. Moreover, the widely held notion that
      people have to be scared or threatened to encourage attitude and behaviour
      changes should be treated with caution. Communication should instead focus on
      efficacy to foster adaptive responses. Statement of contribution What is already
      known on this subject? There is mixed support for the effectiveness of fear
      appeals in persuasive health communication, especially regarding the interaction
      of threat perceptions and coping appraisals for fear and danger control
      processes. The Extended Parallel Process Model - being a current and often
      applied model to investigate the effects of fear appeals - suggests a
      multiplicative relationship between threat perceptions and coping perceptions
      Most studies applying conventional analysis strategies (e.g., [M] ANOVAs)
      indicate that perceptions and appraisals of threat and efficacy are not directly
      related to each other. What does this study add? It demonstrates the parallelism
      and interaction between threat appraisal and coping appraisal processes and
      demonstrates the usefulness of SEM in testing associations within the EPPM. It
      confirms the assumption of an important multiplicative association between threat
      and coping appraisals within the EPPM, while related cognitive processes still
      seem to operate independently. Adaptive responses to persuasive messages are
      mainly triggered using efficacy cues, not threat, which could also be triggered
      by promoting positive emotional experiences (e.g., gain-framing or entertainment
      education).

PMID- 29635863
TI  - Concurrent Drug Unplugging and Permeabilization of Polyprodrug-Gated Crosslinked
      Vesicles for Cancer Combination Chemotherapy.
AB  - Combination chemotherapy with both hydrophobic and hydrophilic therapeutic drugs
      is clinically vital toward the treatment of persistent cancers. Though
      conventional liposomes and polymeric vesicles possessing hydrophobic bilayers and
      aqueous interiors can serve as codelivery nanocarriers, it remains a considerable
      challenge to achieve synchronized release of both types of drugs due to distinct
      encapsulation mechanisms; premature release of water-soluble cargos from unstable
      liposomes and ruptured vesicles is also a major concern. Herein, the fabrication
      of physiologically stable polyprodrug-gated crosslinked vesicles (GCVs) via the
      self-assembly of camptothecin (CPT) polyprodrug amphiphiles and in situ bilayer
      crosslinking through traceless sol-gel reaction is reported. Polyprodrug-GCVs
      possess high CPT loading (>30 wt%) and minimized leakage of encapsulated
      hydrophilic doxorubicin (DOX) hydrochloride due to the suppressed permeability of
      crosslinked membrane, exhibiting extended blood circulation (t 1/2 > 13 h) with
      caged cytotoxicity in physiological circulation. Upon cellular uptake by cancer
      cells, cytosolic reductive milieu-triggered CPT unplugging from vesicle bilayers
      is demonstrated to generate hydrophilic mesh channels and make the membrane
      highly permeable. Concurrently, it will promote DOX corelease from hydrophilic
      lumen (~36-fold increase). The reduction-activated combination chemotherapeutic
      potency based on polyprodrug-GCVs is confirmed by both in vitro and in vivo
      explorations.

PMID- 29635865
TI  - Eye care in young children: a parent survey exploring access and barriers.
AB  - BACKGROUND: A questionnaire was designed to investigate the attitudes of parents
      toward eye care for their young children (4-6-year-olds) and possible barriers to
      accessing eye care for this age group. An exploration was undertaken to determine
      whether these beliefs and barriers are influenced by certain demographic factors
      such as ethnicity, level of parental income, level of parental education,
      confidence with speaking English and a reported family history of eye problems.
      METHODS: A total of 1,317 questionnaires (hard copies) were distributed to
      parents of children in primary school reception and year one classes (ages four
      to six) from 14 schools across five London boroughs. Ninety online surveys were
      sent to parents at two further London schools. All questionnaires were anonymous.
      RESULTS: A total of 384 completed questionnaires were analysed (27 per cent
      response rate). Three hundred and thirty-eight parents (24 per cent) completed
      the 'parental knowledge' section of the questionnaire. Of all responses, 65 per
      cent (n = 249) were from parents whose children attended a school where a program
      of school entry vision screening took place. Of these, 15 per cent (n = 36) of
      parents reported that they were aware of the screening program. Barriers to
      accessing eye care for their children were reported by 38 per cent (n = 153) of
      parents/carers who responded. Twelve per cent (n = 47) reported not knowing how
      to access an eye test for their child and 12 per cent (n = 47) reported that they
      were concerned their child would be given glasses that were not needed. When
      compared to parents from White ethnic groups, parents from African/Afro-Caribbean
      ethnic groups were more likely to report not knowing how to access an age
      appropriate eye test for their child (p = 0.001). Parents of African/Afro
      Caribbean ethnic origins were statistically more likely to report barriers to eye
      care (p = 0.001). CONCLUSION: The study provides evidence of some parental
      misconceptions around eye care for young children and some barriers to access.
      Possible solutions to this are discussed.

PMID- 29635866
TI  - Prevalence of fecal viruses and bacteriophage in Canadian farmed mink (Neovison
      vison).
AB  - Recent viral metagenomic studies have demonstrated the diversity of eukaryotic
      viruses and bacteriophage shed in the feces of domestic species. Although enteric
      disease is a major concern in the commercial mink farming industry, few etiologic
      agents have been well characterized. This study aimed to identify viruses shed in
      the fecal matter of clinically healthy commercial mink from 40 southern Ontario
      farms. Viral RNA was extracted from 67 pooled fecal samples (30 adult female mink
      and 37 kit) and amplified for Illumina sequencing on the NextSeq platform, and
      the resulting contigs were trimmed and assembled using Trimmomatic 0.36.0 and
      Spades 3.8.0 in iVirus (CyVerse, AZ, USA) and SeqMan NGen 12 (DNAStar, WI, USA).
      Identification of assembled sequences >100 bp (Geneious 10.1.3) showed an
      abundance of bacteriophage sequences, mainly from families Siphoviridae (53%),
      Podoviridae (22%), Myoviridae (20%), Inoviridae (1%), Leviviridae (0.04%),
      Tectiviridae (0.01%), and Microviridae (0.01%). A diverse range of vertebrate
      viruses were detected, of which posavirus 3, mink bocavirus, gyroviruses, and
      avian-associated viruses were most abundant. Additionally, sequences from
      nonvertebrate viruses with water and soil-associated amebal and algal hosts were
      also highly prevalent. The results of this study show that viruses shed in the
      fecal matter of healthy commercial mink are highly diverse and could be closely
      associated with diet, and that more research is necessary to determine how the
      detected viruses may impact mink health.

PMID- 29635867
TI  - Is refreshing in working memory impaired in older age? Evidence from the retro
      cue paradigm.
AB  - Impairments in refreshing have been suggested as one source of working memory
      (WM) deficits in older age. Retro-cues provide an important method of
      investigating this question: a retro-cue guides attention to one WM item, thereby
      arguably refreshing it and increasing its accessibility compared with a no-cue
      baseline. In contrast to the refreshing deficit hypothesis, intact retro-cue
      benefits have been found in older adults. Refreshing, however, is assumed to
      boost not one but several WM representations when sequentially applied to them.
      Hence, intact refreshing requires the flexible switching of attention among WM
      items. So far, it remains an open question whether older adults show this
      flexibility. Here, we investigated whether older adults can use multiple cues to
      sequentially refresh WM representations. Younger and older adults completed a
      continuous-color delayed-estimation task, in which the number of retro-cues (0,
      1, or 2) presented during the retention interval was manipulated. The results
      showed a similar retro-cue benefit for younger and older adults, even in the two
      cue condition in which participants had to switch attention between items to
      refresh representations in WM. These findings suggest that the capacity to use
      cues to refresh information in visual WM may be preserved with age.

PMID- 29635869
TI  - The epidemiology of Helicobacter pylori infection in Europe and the impact of
      lifestyle on its natural evolution toward stomach cancer after infection: A
      systematic review.
AB  - BACKGROUND: Helicobacter pylori is a recognized cause of stomach cancer, but only
      a fraction of infected subjects develop cancer. This systematic review 1,
      summarizes the prevalence of infection with this bacterium in Europe; and 2,
      reviews the possible impact of particular lifestyles in progression from
      infection to stomach cancer. MATERIALS AND METHODS: A systematic literature
      search was conducted in two databases by two independent investigators. Studies
      describing prevalence of infection among European healthy adult populations and
      worldwide studies analyzing the impact of lifestyle factors in association with
      H. pylori on stomach cancer risk were included. RESULTS: Variable H. pylori
      infection prevalence was observed depending on region and study period. The
      lowest infection prevalences were found in Northern Europe, while the highest
      were in Eastern and Southern Europe, up to 84% in Portugal and Poland. Studies on
      smoking, salt, and meat consumption demonstrated increased risks of developing
      stomach cancer among H. pylori-infected individuals, while studies relating the
      intake of fruit, vegetables, and vitamins demonstrated decreased risks, but the
      levels of significance differed importantly between studies. No significant
      interaction could be found for alcohol consumption or physical activity.
      CONCLUSIONS: Recent data showed remaining high H. pylori infection rates in
      several European regions. This systematic review suggests that a number of
      correctable lifestyle factors could impact the disease progression toward H.
      pylori-associated stomach cancer. However, additional research is required to
      determine the potential role of targeted interventions in reducing stomach cancer
      development after H. pylori infection.

PMID- 29635868
TI  - Mesenchymal Stem Cells (MSC) Derived from Induced Pluripotent Stem Cells (iPSC)
      Equivalent to Adipose-Derived MSC in Promoting Intestinal Healing and Microbiome
      Normalization in Mouse Inflammatory Bowel Disease Model.
AB  - Cellular therapy with allogeneic or autologous mesenchymal stem cells (MSC) has
      emerged as a promising new therapeutic strategy for managing inflammatory bowel
      disease (IBD). However, MSC therapy ideally requires a convenient and relatively
      homogenous cell source (typically bone marrow or adipose tissues) and the ability
      to generate cells with stable phenotype and function. An alternative means of
      generating allogeneic MSC is to derive them from induced pluripotent stem cells
      (iPSC), which could in theory provide an indefinite supply of MSC with well
      defined phenotype and function. Therefore, we compared the effectiveness of iPSC
      derived MSC (iMSC) and adipose-derived MSC (adMSC) in a mouse model of IBD
      (dextran sodium sulfate-induced colitis), and investigated mechanisms of
      intestinal protection. We found that iMSC were equivalent to adMSC in terms of
      significantly improving clinical abnormalities in treated mice and reducing
      lesion scores and inflammation in the gut. Administration of iMSC also stimulated
      significant intestinal epithelial cell proliferation, increased in the numbers of
      Lgr5+ intestinal stem cells, and increased intestinal angiogenesis. In addition,
      the microbiome alterations present in mice with colitis were partially restored
      to resemble those of healthy mice following treatment with iMSC or adMSC. Thus,
      iMSC administration improved overall intestinal health and healing with
      equivalent potency to treatment with adMSC. This therefore is the first report of
      the effectiveness of iMSC in the treatment of IBD, along with a description of
      unique mechanisms of action with respect to intestinal healing and microbiome
      restoration. Stem Cells Translational Medicine 2018;7:456-467.

PMID- 29635870
TI  - Efficient Hydrogen Production on a 3D Flexible Heterojunction Material.
AB  - A novel heterojunction material, with electron-rich graphdiyne as the host and
      molybdenum disulfide as the catalytic center (eGDY/MDS), to produce
      ultraefficient hydrogen-evolution reaction (HER) at all pH values is described.
      It is a surprise that the metallic conductor combined from two semiconductor
      materials, eGDY and MDS, leads to optimal free energy (DeltaGH ) and enhancement
      in the intrinsic HER catalytic performances. The calculated and experimental
      results indicate that eGDY/MDS shows greatly enhanced catalytic activities and
      high stabilities in both acidic and alkaline conditions; these approach the
      outstanding performances of the state-of-the-art noble-metal-based catalysts. The
      eGDY/MDS shows better activity than Pt/C in alkaline media and remarkable
      enhancement in photocurrent density. The high catalytic activity of eGDY/MDS
      originates from facilitated electronic transfer kinetics, high conductivity, more
      exposed catalytic active sites, and excellent mass transport.

PMID- 29635871
TI  - Active Sites Engineering toward Superior Carbon-Based Oxygen Reduction Catalysts
      via Confinement Pyrolysis.
AB  - Developing efficient and low-cost defective carbon-based catalysts for the oxygen
      reduction reaction (ORR) is essential to metal-air batteries and fuel cells.
      Active sites engineering toward these catalysts is highly desirable but
      challenging to realize boosted catalytic performance. Herein, a sandwich-like
      confinement route to achieve the controllable regulation of active sites for
      carbon-based catalysts is reported. In particular, three distinct catalysts
      including metal-free N-doped carbon (NC), single Co atoms dispersed NC (Co-N-C),
      and Co nanoparticles-contained Co-N-C (Co/Co-N-C) are controllably realized and
      clearly identified by synchrotron radiation-based X-ray spectroscopy.
      Electrochemical measurements suggest that the Co/Co-N-C catalyst delivers
      optimized ORR performance due to the rich Co-Nx active sites and their
      synergistic effect with metallic Co nanoparticles. This work provides deep
      insight for rationally designing efficient ORR catalyst based on active sites
      engineering.

PMID- 29635873
TI  - Once daily oral extended-release hydrocodone as analgesia following tibial
      plateau leveling osteotomy in dogs.
AB  - OBJECTIVE: To determine the efficacy of oral extended-release hydrocodone
      compared with oral firocoxib for analgesia following tibial plateau leveling
      osteotomy surgery in dogs in a hospital setting. STUDY DESIGN: Prospective,
      randomized, blinded, clinical trial. ANIMALS: Thirty-six client-owned dogs
      weighing 25-43 kg with unilateral hindlimb lameness and cranial cruciate ligament
      rupture. METHODS: Dogs were assigned to 1 of 2 groups (n = 18/group). Group 1
      received hydrocodone 3 mg/kg orally every 24 hours, and group 2 received
      firocoxib 5 mg/kg orally every 24 hours. Both hydrocodone and firocoxib
      (according to group assignment) were provided as preemptive analgesia 10 hours
      before induction to anesthesia and then every 24 hours for the remainder of the
      study period The level of analgesia was compared between treatments on the basis
      of a modified Glasgow Composite Pain Score (mGCPS) in each dog, the number of
      dogs requiring rescue analgesia (hydromorphone 0.05 mg/kg subcutaneously),
      pressure platform stance data, and number of adverse events. RESULTS: Nine of 18
      dogs that received hydrocodone and 2/18 dogs that received firocoxib had an mGCPS
      >=6 (P = .02). Two dogs had an mGCPS >=6 three times, and 1 had an mGCPS >=6 two
      times; all 3 of these dogs were in the hydrocodone group. Average postoperative
      peak pressure placed on the affected limb was lower in dogs that received
      hydrocodone (P = .01). Regurgitation and decreased appetite were more common in
      the dogs that received hydrocodone. CONCLUSION: Dogs that were treated with
      hydrocodone exhibited higher pain scores and lower limb function than dogs
      treated with firocoxib under the conditions of our study. CLINICAL SIGNIFICANCE:
      Our results do not provide evidence to justify the administration of extended
      release hydrocodone at 3 mg/kg orally every 24 hours rather than firocoxib at 5
      mg/kg orally every 24 hours in dogs undergoing tibial plateau leveling osteotomy.

PMID- 29635874
TI  - Prediction of taper performance using quasi static FE models: The influence of
      loading, taper clearance and trunnion length.
AB  - The head-neck taper junction has been widely reported to corrode leading to
      adverse tissue reactions. Taper corrosion is a poorly understood phenomenon but
      has been associated with oxide layer damage and ingress of corrosive
      physiological fluids. Micromotion may damage the oxide layer; although little is
      understood about the prevailing stresses which cause this. The ingress of fluid
      around the joint space into the taper will depend on the taper contact position
      and the separation of the interfaces during loading. The current work reports on
      the effect of taper clearances and trunnion length on the taper surface stresses
      and the taper gap opening. These were determined for CoCr/Ti taper interfaces
      using FE under loading conditions including walking and stair climb as well as
      hip simulator load profiles. Shorter trunnions and stair climb loading were shown
      to generate the greatest taper gaps (82 um) and also the largest surface stresses
      (1200 MPa) on the head taper. The largest taper gaps were associated with smaller
      taper contact areas. Clearances within +/-0.1 degrees  had no effect on the taper
      gaps generated, as the tapers engaged over comparable lengths; the taper gap
      opening was dependent upon the taper engagement length rather than location
      (proximal or distal) of contact. The walking profile or variants applied by hip
      simulators, was insufficient to differentiate between taper designs and evaluate
      differences in the magnitudes of taper gaps. The use of more demanding activity
      such as stair climb during in vitro evaluations could provide better predictions
      of taper performance in vivo. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res
      Part B: Appl Biomater, 2018.

PMID- 29635872
TI  - A randomized, blinded, prospective clinical trial of postoperative rehabilitation
      in dogs after surgical decompression of acute thoracolumbar intervertebral disc
      herniation.
AB  - BACKGROUND: Experimental evidence shows benefit of rehabilitation after spinal
      cord injury (SCI) but there are limited objective data on the effect of
      rehabilitation on recovery of dogs after surgery for acute thoracolumbar
      intervertebral disc herniations (TL-IVDH). OBJECTIVE: Compare the effect of basic
      and intensive post-operative rehabilitation programs on recovery of locomotion in
      dogs with acute TL-IVDH in a randomized, blinded, prospective clinical trial.
      ANIMALS: Thirty non-ambulatory paraparetic or paraplegic (with pain perception)
      dogs after decompressive surgery for TL-IVDH. METHODS: Blinded, prospective
      clinical trial. Dogs were randomized (1:1) to a basic or intensive 14-day in
      house rehabilitation protocol. Fourteen-day open field gait score (OFS) and
      coordination (regulatory index, RI) were primary outcomes. Secondary measures of
      gait, post-operative pain, and weight were compared at 14 and 42 days. RESULTS:
      Of 50 dogs assessed, 32 met inclusion criteria and 30 completed the protocol.
      There were no adverse events associated with rehabilitation. Median time to
      walking was 7.5 (2 - 37) days. Mean change in OFS by day 14 was 6.13 (confidence
      intervals: 4.88, 7.39, basic) versus 5.73 (4.94, 6.53, intensive) representing a
      treatment effect of -0.4 (-1.82, 1.02) which was not significant, P=.57. RI on
      day 14 was 55.13 (36.88, 73.38, basic) versus 51.65 (30.98, 72.33, intensive), a
      non-significant treatment effect of -3.47 (-29.81, 22.87), P = .79. There were no
      differences in secondary outcomes between groups. CONCLUSIONS: Early
      postoperative rehabilitation after surgery for TL-IVDH is safe but doesn't
      improve rate or level of recovery in dogs with incomplete SCI.

PMID- 29635875
TI  - Recurrent seascape units identify key ecological processes along the western
      Antarctic Peninsula.
AB  - The western Antarctic Peninsula (WAP) is a bellwether of global climate change
      and natural laboratory for identifying interactions between climate and
      ecosystems. The Palmer Long-Term Ecological Research (LTER) project has collected
      data on key ecological and environmental processes along the WAP since 1993. To
      better understand how key ecological parameters are changing across space and
      time, we developed a novel seascape classification approach based on in situ
      temperature, salinity, chlorophyll a, nitrate + nitrite, phosphate, and silicate.
      We anticipate that this approach will be broadly applicable to other geographical
      areas. Through the application of self-organizing maps (SOMs), we identified
      eight recurrent seascape units (SUs) in these data. These SUs have strong
      fidelity to known regional water masses but with an additional layer of
      biogeochemical detail, allowing us to identify multiple distinct nutrient
      profiles in several water masses. To identify the temporal and spatial
      distribution of these SUs, we mapped them across the Palmer LTER sampling grid
      via objective mapping of the original parameters. Analysis of the abundance and
      distribution of SUs since 1993 suggests two year types characterized by the
      partitioning of chlorophyll a into SUs with different spatial characteristics. By
      developing generalized linear models for correlated, time-lagged external
      drivers, we conclude that early spring sea ice conditions exert a strong
      influence on the distribution of chlorophyll a and nutrients along the WAP, but
      not necessarily the total chlorophyll a inventory. Because the distribution and
      density of phytoplankton biomass can have an impact on biomass transfer to the
      upper trophic levels, these results highlight anticipated links between the WAP
      marine ecosystem and climate.

PMID- 29635877
TI  - Are tree squirrels involved in the circulation of flaviviruses in Italy?
AB  - West Nile virus (WNV), Usutu virus (USUV) and tick-borne encephalitis virus
      (TBEV) are emerging zoonotic flaviviruses (family Flaviviridae), which have
      circulated in Europe in the past decade. A cross-sectional study was conducted to
      assess exposure to these antigenically related flaviviruses in eastern grey
      squirrels (Sciurus carolinensis) in Italy. Seventeen out of 158 (10.8%; CI95% :
      5.9-15.6) squirrels' sera tested through bELISA had antibodies against
      flaviviruses. Specific neutralizing antibodies to WNV, USUV and TBEV were
      detected by virus neutralization tests. Our results indicate that tree squirrels
      are exposed to Culex and tick-borne zoonotic flaviviruses in Italy. Moreover,
      this study shows for the first time USUV and TBEV exposure in grey squirrels,
      broadening the host range reported for these viruses. Even though further studies
      are needed to define the real role of tree squirrels in the epidemiology of
      flaviviruses in Europe, this study highlights that serology could be an effective
      approach for future investigations aimed at broadening our knowledge about the
      species exposed to these zoonotic infections.

PMID- 29635876
TI  - Intravenous immunoglobulin for maintenance treatment of multifocal motor
      neuropathy: A multi-center, open-label, 52-week phase 3 trial.
AB  - Intravenous immunoglobulin (IVIg) therapy is currently the only established
      treatment in patients with multifocal motor neuropathy (MMN), and many patients
      have an IVIg-dependent fluctuation. We aimed to investigate the efficacy and
      safety of every 3 week IVIg (1.0 g/kg) for 52 weeks. This study was an open-label
      phase 3 clinical trial, enrolling 13 MMN patients. After an induction IVIg
      therapy (0.4 g/kg/d for 5 consecutive days), maintenance dose (1.0 g/kg) was
      given every 3 weeks for 52 weeks. The major outcome measures were the Medical
      Research Council (MRC) sum score and hand-grip strength at week 52. This trial is
      registered with ClinicalTrials.gov, number NCT01827072. At week 52, 11 of the 13
      patients completed the study, and all 11 had a sustained improvement. The mean
      (SD) MRC sum score was 85.6 (8.7) at the baseline, and 90.6 (12.8) at week 52.
      The mean grip strength was 39.2 (30.0) kPa at the baseline and 45.2 (32.8) kPa at
      week 52. Two patients dropped out because of adverse event (dysphagia) and
      decision of an investigator, respectively. Three patients developed coronary
      spasm, dysphagia, or inguinal herniation, reported as the serious adverse events,
      but considered not related with the study drug. The other adverse effects were
      mild and resolved by the end of the study period. Our results show that
      maintenance treatment with 1.0 g/kg IVIg every 3 week is safe and efficacious for
      MMN patients up to 52 weeks. Further studies are required to investigate optimal
      dose and duration of maintenance IVIg for MMN.

PMID- 29635878
TI  - In Praise of Value-Interrogating Sociology.

PMID- 29635879
TI  - Baseline symptom severity and therapeutic success in a large prospective trial of
      sacral neuromodulation therapy for overactive bladder patients.
AB  - INTRODUCTION: The InSite trial is a prospective, multicenter post-approval study
      of subjects receiving sacral neuromodulation (SNM) therapy with the InterStim(r)
      System. Enrolled subjects had bothersome symptoms of overactive bladder (OAB).
      The purpose of this analysis was to determine if severity of baseline symptoms
      had an impact on clinical outcomes. METHODS: For device implant, therapeutic
      success was defined as a  >=50% improvement in average leaks/day, or in voids/day
      or a return to normal voiding frequency. Groups were dichotomized into less
      versus more severe based on median number of leaks and voids. Subjects were
      grouped as less severe <2 leaks/day for UI; <11 voids/day for UF and more severe
      >=2 leaks/day for UI;  >=11 voids/day for UF. Therapeutic success at 12 and 24
      months were compared between groups. RESULTS: Three hundred and forty subjects
      completed test stimulation and 272 (80%) subjects received a full system implant.
      On average UI subjects had 1.3 leaks/day in the less severe group and 4.5
      leaks/day in the more severe group. UI success rates were not statistically
      different between severity groups at 12 months or 24 months). At baseline, on
      average UF subjects had 9.4 voids/day for the less severe group and 15.1
      voids/day for the more severe group. UF success rates were not statistically
      different between severity groups at 12 months or 24 months. CONCLUSION: Data
      evaluating efficacy based on symptom severity demonstrates that SNM is effective
      in treating both less severe and more severely affected groups for both UI and UF
      at 12 and 24 months.

PMID- 29635880
TI  - Avoiding or enduring painful sex? A prospective study of coping and psychosexual
      function in vulvovaginal pain.
AB  - BACKGROUND: Recurring vulvovaginal pain is common, with evident effects on
      affected women's lives. Little is known about how affected women cope with
      painful sexual activities and how coping relates to pain intensity and
      psychosexual functioning over time. This prospective study explored the impact of
      avoidance and endurance on sexual function over time. Additionally, patterns of
      coping were studied on an individual level to increase knowledge about coping and
      its relation to psychosexual functioning. METHODS: One hundred and seventeen
      women, 18-35 years old, with recurring vulvovaginal pain answered questionnaires
      at two measurement points, five months apart, assessing avoidance and endurance
      coping, pain intensity and psychosexual functioning. A multiple regression model
      explored the predictive value of avoidance and endurance on sexual function over
      time. Cluster analyses investigated patterns of coping and stability within the
      clusters. These subgroups were compared on psychosexual outcomes. RESULTS:
      Avoidance at baseline was the only significant predictor of sexual function five
      months later. Distinct and stable subgroups with different patterns of coping
      were identified, where avoidance and endurance coping were used both separately
      and combined. Women who both avoided and endured had the most unfavourable
      outcomes in terms of psychosexual functioning. CONCLUSIONS: Avoidance of sexual
      activities was related to reduced sexual function over time, which calls for
      attention and clinical interventions targeting avoidance. Additionally, women who
      both avoid and endure sexual activities despite pain possibly need tailored
      interventions, as women with this coping pattern reported the lowest levels of
      psychosexual functioning. SIGNIFICANCE: In this prospective study, avoidance of
      sexual activities predicted sexual function over time, when controlling for pain
      intensity. Subgroups of women using distinct patterns of coping were identified.
      Those who both avoided and endured had the lowest levels of psychosexual
      functioning.

PMID- 29635881
TI  - I will take my heart failure 'lactate-free' please.

PMID- 29635882
TI  - Identification of genes related to chlamydospore formation in Clonostachys rosea
      67-1.
AB  - Chlamydospores are specific structures that are of great significance to the
      commercialization of fungal biopesticides. To explore the genes associated with
      chlamydospore formation, a biocontrol fungus Clonostachys rosea 67-1 that is
      capable of producing resistant spores under particular conditions was
      investigated by transcriptome sequencing and analysis. A total of 549,661,174
      clean reads were obtained, and a series of differentially expressed genes
      potentially involved in fungal chlamydospore formation were identified. At 36 hr,
      67 and 117 genes were up- and downregulated in C. rosea during chlamydospore
      production, compared with the control for conidiation, and 53 and 24 genes were
      up- and downregulated at 72 hr. GO classification suggested that the
      differentially expressed genes were related to cellular component, biological
      process, and molecular function categories. A total of 188 metabolism pathways
      were linked to chlamydospore production by KEGG analysis. Sixteen differentially
      expressed genes were verified by reverse transcription quantitative PCR, and the
      expression profiles were consistent with the transcriptome data. To the best of
      our knowledge, it is the first report on the genes associated with chlamydospore
      formation in C. rosea. The results provide insight into the molecular mechanisms
      underlying C. rosea sporulation, which will assist the development of fungal
      biocontrol agents.

PMID- 29635883
TI  - A person-centred approach to family carer needs assessment and support in
      dementia community care in Western Australia.
AB  - This feasibility study aimed to identify and address the support needs of family
      carers (FCs) of people living with dementia and to assess whether the use of the
      Carer Support Needs Assessment Tool (CSNAT) intervention in home-based care was
      acceptable and relevant to FCs. The CSNAT intervention comprised two FC support
      needs assessment visits, 7 weeks apart, plus associated actions addressing
      prioritised needs by the Client Care Advisors of a community care service in
      Western Australia in 2015. Telephone interviews were conducted with FCs on their
      experience using the CSNAT at the end of the intervention. Twenty-one FCs were
      involved in the intervention and 15 of them completed the feedback interviews.
      Care recipients had moderate to severe dementia. The top five support needs
      reported by FCs were: having time to yourself in the day; knowing what to expect
      in the future; practical help in the home; looking after your own health and
      dealing with your feelings and worries. Three themes summarised their experience:
      a straightforward structured approach; awareness, acknowledgement and acceptance
      of their situation; and provision of support. FCs appreciated the opportunity to
      be heard and acknowledged, to have their practical and psychosocial support needs
      facilitated, to identify what is important to them and to receive a response in a
      timely manner. The CSNAT approach offered a structured carer-led, person-centred,
      supportive intervention that facilitated discussion between the family carer and
      the service provider about support needs and strategies to address them.

PMID- 29635884
TI  - Deposition of inhaled nanoparticles is reduced in subjects with COPD and
      correlates with the extent of emphysema: proof of concept for a novel diagnostic
      technique.
AB  - BACKGROUND: The diagnosis of chronic obstructive pulmonary disease (COPD) is
      often based on spirometry, which is not sensitive to early emphysema. We have
      recently described a method for assessing distal airspace dimensions by measuring
      recovery of nanoparticles in exhaled air after a single-breath inhalation
      followed by breath-hold. Recovery refers to the non-deposited particle fraction.
      The aim of this study was to explore differences in the recovery of exhaled
      nanoparticles in subjects with COPD and never-smoking controls. A secondary aim
      was to determine whether recovery correlates with the extent of emphysema.
      METHOD: A total of 19 patients with COPD and 19 controls underwent three repeats
      of single-breath nanoparticle inhalation followed by breath-hold. Particle
      concentrations in the inhaled aerosol, and in an alveolar sample exhaled after
      breath-hold, were measured to obtain recovery. FINDINGS: The patients with COPD
      had a significantly higher mean recovery than controls, 0.128 +/- 0.063 versus
      0.074 +/- 0.058; P = 0.010. Also, recovery correlated significantly with computed
      tomography (CT) densitometry variables (P<0.01) and diffusing capacity for carbon
      monoxide (DL,CO ; P = 0.002). INTERPRETATION: Higher recovery for emphysema
      patients, relative to controls, is explained by larger diffusion distances in
      enlarged distal airspaces. The nanoparticle inhalation method shows potential to
      be developed towards a tool to diagnose emphysema.

PMID- 29635885
TI  - Fused Isoindigo Ribbons with Absorption Bands Reaching Near-Infrared.
AB  - Through fusing isoindigo (IID) units at 6,7;6',7'-positions, a series of new near
      infrared (NIR) absorbing and stable ribbon-like conjugated molecules, namely
      nIIDs in which n represents the number of IID units, have been synthesized. The
      optical band gaps of the molecules are lowered from 2.03 eV of 1IID to 1.12 eV of
      6IID with the increase of the conjugation length. 3IID, 4IID, and 6IID have
      strong absorption in the NIR region and exhibit photothermal conversion
      efficiencies of greater than 50 % under laser irradiation at lambda=808 nm.

PMID- 29635886
TI  - Evaluation of the association between strong ion acid-base disturbances and
      mortality in dogs: a retrospective study.
AB  - Acid-base abnormalities are frequently encountered in veterinary emergency and
      critical care, but information regarding the prognostic value of these findings
      is limited. Several systems for analysing acid-base disturbances have been
      reported, but the prognostic abilities of these systems have not been compared in
      dogs. The objectives of this retrospective study were to determine if the
      commonly used acid-base interpretation methods (Henderson-Hasselbalch, Stewart
      and semi-quantitative) have prognostic value, and to compare the performance of
      the three methods. Electronic medical records were searched to create a database
      containing point-of-care blood-gas, electrolyte and serum chemistry values for
      1024 dogs assessed at a university teaching hospital. Dogs with contemporaneous
      blood-gas analysis, blood lactate and serum biochemistry samples were eligible
      for study, and only the first recorded analyses for each patient visit were
      included. Components of the Henderson-Hasselbalch, Stewart and semi-quantitative
      methods were calculated. To assess prognostic ability and to compare analysis
      system performance, receiver-operating characteristic (ROC) curves for survival
      to hospital discharge were created. Of the 1024 dogs identified, case fatality
      rate was 23.8%. Area under the ROC curve did not exceed 0.63 for any calculated
      variable. Performance of all three analysis systems was similar. While some acid
      base abnormalities identified were associated with mortality, no individual
      abnormality or system output yielded sensitive and specific cut-off values for
      mortality prediction, and no interpretation method outperformed the others. This
      study suggests that initial acid-base abnormalities have limited prognostic
      utility and that various analysis systems can be used to assess acid-base
      disturbances in critically ill dogs.

PMID- 29635887
TI  - Associations between maternal mental health and early child wheezing in a South
      African birth cohort.
AB  - BACKGROUND: Wheezing in early childhood is common and has been identified in high
      income countries (HIC) as associated with maternal antenatal or postnatal
      psychosocial risk factors. However, the association between maternal mental
      health and childhood wheezing has not been well studied in low and middle-income
      countries (LMIC), such as South Africa. METHODS: A total of 1137 pregnant women
      over 18 year old, between 20 and 28 weeks' gestation, and attending either of two
      catchment area clinics were enrolled in a South African parent study, the
      Drakenstein Child Health Study (DCHS). Psychosocial risk factors including
      maternal depression, psychological distress, early adversity, and intimate
      partner violence (IPV), were measured antenatally and postnatally by validated
      questionnaires. Two outcomes were evaluated: Presence of wheeze (at least one
      episode of child wheeze during the first 2 years of life); and recurrent wheeze
      (two or more episodes of wheezing in a 12-month period). Logistic regression was
      used to investigate the association between antenatal or postnatal psychosocial
      risk factors and child wheeze, adjusting for clinical and socio-demographic
      covariates. RESULTS: Postnatal psychological distress and IPV were associated
      with both presence of wheeze (adjusted OR = 2.09, 95%CI: 1.16-3.77 and 1.63,
      95%CI: 1.13-2.34, respectively), and recurrent child wheeze (adjusted OR = 2.26,
      95%CI: 1.06-4.81 and 2.20, 95%CI: 1.35-3.61, respectively). CONCLUSION: Maternal
      postnatal psychological distress and IPV were associated with wheezing in early
      childhood. Thus, screening and treatment programs to address maternal
      psychosocial risk factors may be potential strategies to reduce the burden of
      childhood wheeze in LMICs.

PMID- 29635888
TI  - Repetitive and compulsive-like behaviors lead to cognitive dysfunction in
      Disc1Delta2-3/Delta2-3 mice.
AB  - Disrupted-in-schizophrenia 1 (Disc1) is a key molecular driver for the biology of
      mental diseases. In order to investigate its role in brain function, we
      previously generated mice lacking exons 2 and 3 of Disc1 on a C57BL/6J genetic
      background (Disc1Delta2-3/Delta2-3 mice), which have a deficiency of the full
      length Disc1 protein. In the present study, we examined the role of Disc1 in
      cognitive function using a touchscreen-based visual discrimination (VD) task in
      which mice had to discriminate 1 of 2 stimuli simultaneously displayed on the
      screen and received a liquid reward. Disc1Delta2-3/Delta2-3 mice showed impaired
      performance in the VD task, and this was mainly attributed to the perseverative
      response being significantly stronger than that in wild-type (WT) mice.
      Furthermore, the numbers of marbles buried in the marble burying test and
      nestlets shredded in the nestlet shredding test by Disc1Delta2-3/Delta2-3 mice
      were significantly higher than those by WT mice, suggesting
      perseverative/compulsive behaviors by Disc1Delta2-3/Delta2-3 mice. A treatment
      with clozapine ameliorated behavioral deficits in the VD and marble burying
      tasks. c-Fos expression was significantly stronger in the dorsomedial striatum
      (DMS), but not the dorsolateral striatum (DLS) after the first VD session in
      Disc1Delta2-3/Delta2-3 mice than in WT mice. The treatment of mice that had
      previously expressed hM3Dq in the DMS with clozapine-N-oxide (CNO) impaired
      performance in the VD task. These results suggest that cognitive impairments
      accompanied by perseverative/compulsive behaviors in Disc1Delta2-3/Delta2-3 mice
      are associated with hyperactivity of the DMS.

PMID- 29635889
TI  - Neural architecture in lymphoid organs: Hard-wired antigen presenting cells and
      neurite networks in antigen entrance areas.
AB  - INTRODUCTION: Recently, we found abundant innervation of antigen presenting cells
      that were reached and enclosed by single neurites. These neurally hard-wired
      antigen presenting cells (wAPC) could be observed in the T-cell zone of
      superficial cervical lymph nodes of rats and other mammalians, including humans.
      METHODS: As a consequence, we investigated lymph nodes at many different
      anatomical positions as well as all primary and secondary lymphoid organs (SLO)
      in rodents for a similar morphology of innervation regarding antigen presenting
      cells known in those tissues. RESULTS: As a result, we confirmed wAPC in lymph
      nodes independent from their draining areas and anatomical positions but also in
      all other T-cell zones of lymphoid organs, like Peyer's patches, NALT and BALT,
      as well as in the thymic medulla. Other cells were innervated in a similar
      fashion but with seemingly missing antigen presenting capacity. Both types of
      innervated immune cells were observed as being also present in the dermis of the
      skin. Only in the spleen wAPC could not be detected. Beyond this systematic
      finding, we also found another regular phenomenon: a dense network of neurites
      that stained for neurofilament always in antigen entrance areas of lymphoid
      organs (subsinoidal layer of lymph nodes, subepithelial dome of Peyer's patches,
      subsinoidal layer of the splenic white pulp, margins of NALT and BALT). Lastly,
      also thymic epithelial cells (TEC) restricted to the corticomedullary junction of
      the thymus showed similar neurofilament staining. CONCLUSIONS: Therefore, we
      propose much more hard-wired and probably afferent connections between lymphoid
      organs and the central nervous system than is hitherto known.

PMID- 29635890
TI  - MiR-21 attenuates apoptosis-triggered by amyloid-beta via modulating PDCD4/
      PI3K/AKT/GSK-3beta pathway in SH-SY5Y cells.
AB  - Alzheimer's disease (AD) remains the most common neurodegenerative disease with
      amyloid beta (Abeta) formatted and accumulated. Recently, microRNAs have been
      identified as significant regulators in neurogenesis of the central nervous
      system (CNS). However, the biological role of miR-21 in AD remains unclear. The
      purpose of our study was to investigate the mechanism of miR-21 in AD. AD model
      was established using 20 MUM Abeta1-42 in SH-SY5Y cells. Abeta1-42 can induce
      cell apoptosis via increasing Bax and decreasing Bcl-2 protein levels. Meanwhile,
      we observed that miR-21 was remarkably elevated by indicated Abeta1-42 in vitro.
      Subsequently, miR-21 mimics were transfected into SH-SY5Y cells and it was found
      that miR-21 can inhibit cell apoptosis induced by Abeta1-42. Programmed cell
      death protein 4 (PDCD4), an important tumor suppressor in various cancers has
      been reported to prevent AKT activation. The phosphatidylinositol 3-kinase
      (PI3K)/AKT/GSK-3beta pathway can release a survival signal to protect from
      multiple injuries. Interestingly, it was found that PDCD4 was involved in miR-21
      repressed cell apoptosis in AD models. miR-21 mimics can increase the PI3K, AKT
      and GSK-3beta activity while PDCD4 ovexexpression inhibited their activity
      respectively. Moreover, knockdown of PDCD4 can rescue PI3K/AKT/GSK-3beta pathway
      in SH-SY5Y cells. Taken these together, it was suggested by our data that miR-21
      can exert protective roles in AD, which might be dependent on PDCD4/PI3K/AKT/GSK
      3beta signaling pathway in vitro.

PMID- 29635891
TI  - Phloretin either alone or in combination with duloxetine alleviates the STZ
      induced diabetic neuropathy in rats.
AB  - Diabetic neuropathy (DN) is one of most disabling disorder complicating diabetes
      mellites (DM), which affects more than 50% of the all diabetic patients during
      the disease course. Duloxetine (DX) is one of the first-line medication that
      approved by FDA for management of DN, nevertheless, it is too costly and has many
      adverse effects. Recently, phloretin (PH) exhibited powerful euglycemic,
      antihyperlipidemic, antioxidant, and anti-inflammatory activities. Therefore, we
      investigated the in vivo possible antineuropathic activity of phloretin, besides,
      its modulating effects on duloxetine potency, in a rat model of DN. Twelve-week
      old male Wistar rats received a single intraperitoneal injection of 55 mg/kg STZ
      to induce DM. Either DX (30 or 15 mg/kg dissolved in distilled water), PH (50 0r
      25 mg/kg dissolved in 0.5% DMSO) or a combination of 15 mg/kg DX and 25 mg/kg PH,
      used daily orally for 4 weeks to treat DN, starting from the end of the 4th week
      of DM development, when DN confirmed. Our finding showed that both DX and PH dose
      dependently improved behavioral parameters (with the superiority of DX), sciatic
      nerve tissue antioxidant state, and suppressed tissue inflammatory cytokine,
      besides, they abrogated the tissue histopathological changes (with the
      superiority of PH). Moreover, DX augmented the DM metabolic disturbance and
      hepatic dysfunction, however, PH effectively amended these disorders.
      Furthermore, the low-dose combination of both, had the merits of both
      medications, with the alleviation of their disadvantages. Therefore, phloretin
      could be a promising agent in the management of DN either alone or in combination
      with duloxetine.

PMID- 29635892
TI  - Animal models and natural products to investigate in vivo and in vitro
      antidiabetic activity.
AB  - Diabetes mellitus is a chronic disease which has high prevalence. The deficiency
      in insulin production or impaired insulin function is the underlying cause of
      this disease. Utilization of plant sources as a cure of diabetes has rich
      evidence in the history. Recently, the traditional medicinal plants have been
      investigated scientifically to understand the underlying mechanism behind
      antidiabetic potential. In this regard, a substantial number of in vivo and in
      vitro models have been introduced for investigating the bottom-line mechanism of
      the antidiabetic effect. A good number of methods have been reported to be used
      successfully to determine antidiabetic effects of plant extracts or isolated
      compounds. This review encompasses all the possible methods with a list of
      medicinal plants which may contribute to discovering a novel drug to treat
      diabetes more efficaciously with the minimum or no side effects.

PMID- 29635893
TI  - MicroRNA-30b promotes lipopolysaccharide-induced inflammatory injury and
      alleviates autophagy through JNK and NF-kappaB pathways in HK-2 cells.
AB  - BACKGROUND: Acute kidney injury (AKI) is an abrupt loss of kidney function.
      MicroRNA-30b (miR-30b) has been reported to be involved in the inflammatory
      reaction of a variety of diseases. However, the role of miR-30b in AKI remains
      unknown. In this research, we aimed to investigate the role of miR-30b in
      lipopolysaccharide (LPS)-induced kindey inflammatory injury in vitro and in vivo.
      METHODS: In vitro, after miR-30b mimic/inhibitor transfection and/or LPS
      treatment, the viability, apoptosis, autophagy and inflammatory cytokines
      releases, as well as activation of c-Jun-N-terminal kinase (JNK) and nuclear
      factor-kappa B (NF-kappaB) pathways were detected by cell counting kit-8 (CCK-8)
      assay, flow cytometry, qRT-PCR, enzyme-linked immunosorbent assay (ELISA) and
      western blot, respectively. In vivo, after LPS treatment and/or anti-miR-30b
      administration, the levels of creatinine, the activities of alanine
      aminotransferase (ALT) and histologic scores, as well as concentrations of
      inflammatory cytokines were assessed by creatinine assay kit, ALT assay kit and
      ELISA, respectively. RESULTS: LPS inhibited HK-2 cell viability and induced HK-2
      cell apoptosis, autophagy and the releases of inflammatory cytokines.
      Overexpression of miR-30b promoted LPS-induced HK-2 cell viability inhibition,
      cell inflammatory cytokines releases, cell apoptosis induction and activation of
      JNK and NF-kappaB signaling pathways, but inhibited LPS-induced HK-2 cell
      autophagy. Suppression of miR-30b had opposite effects. Moreover, suppression of
      miR-30b alleviated the LPS-induced kidney injury in mice model by decreasing
      creatinine level, ALT activity and histologic scores, as well as concentrations
      of inflammatory cytokines. CONCLUSION: miR-30b participated in the LPS-induced
      kindey inflammatory injury in vitro and in vivo.

PMID- 29635894
TI  - Pterostilbene inhibits MTA1/HDAC1 complex leading to PTEN acetylation in
      hepatocellular carcinoma.
AB  - PURPOSE: The aim of this study is to investigate the inhibition of cancer growth
      by pterostilbene through Metastasis-Associated Protein 1 (MTA1) and the histone
      deacetylase 1 (HDAC1) complex in hepatocellular carcinoma (HCC). METHODS: We
      investigate the antitumor effects of pterostilbene (PTER) in HCC. The SMMC-7721
      hepatoma cell line was cultured and treated with PTER for different time
      depending on the experiment. After treatment, we tested the cellular expression
      of proteins by Western blot and the expression of MTA1 mRNA by real-time PCR. And
      the immunoprecipitation was performed to confirm the acetylation in PTEN. Animal
      models have been established to confirm the anti-cancer effects of PTER. RESULTS:
      PTER treatment could downregulate the expression of MTA1, and HDAC1 and elevates
      the Ac-PTEN ratio in tumors. The results suggest that PTER can decrease the
      expression of MTA1 and destabilize the MTA1/HDAC1 complex allowing
      acetylation/activation of PTEN on Lys402 site. The expression of MTA1 may be
      linked to cell apoptosis and invasion in HCC. CONCLUSION: We demonstrated that
      PTER suppressed the growth, and invasion of HCC and was effective in regulating
      the levels of the MTA1/HDAC1/NuRD complex, promoting PTEN acetylation and
      apoptosis in HCC. Our findings suggest that the novel epigenetic nature of PTER
      anticancer activity opens up new avenues for primary chemoprevention, as well as
      anticancer and antimetastatic treatment.

PMID- 29635895
TI  - Flavonoids as acetylcholinesterase inhibitors: Current therapeutic standing and
      future prospects.
AB  - BACKGROUND: Acetylcholinesterase (AChE), a serine hydrolase, is primarily
      responsible for the termination of signal transmission in the cholinergic system,
      owing to its outstanding hydrolyzing potential. Its substrate acetylcholine
      (ACh), is a neurotransmitter of the cholinergic system, with a predominant effect
      on motor neurons involved in memory formation. So, by decreasing the activity of
      this enzyme by employment of specific inhibitors, a number of motor neuron
      disorders such as myasthenia gravis, glaucoma, Lewy body dementia, and
      Alzheimer's disease, among others, can be treated. However, the current-available
      AChE inhibitors have several limitations in terms of efficacy, therapeutic range,
      and safety. SCOPE AND APPROACH: Primarily due to the non-compliance of current
      therapies, new, effective and safe inhibitors are being searched for, especially
      those which act through multiple receptor sites, but do not elicit undesirable
      effects. In this regard, the evaluation of phytochemicals such as flavonoids, can
      be a rational approach. The therapeutic potential of flavonoids has already been
      recognized agaisnt several ailments. This review deals with various plant-derived
      flavonoids, their preclinical potential as AChE inhibitors, in established
      assays, possible mechanisms of action, and structural activity relationship
      (SAR). RESULTS AND CONCLUSIONS: Subsequently, a number of plant-derived
      flavonoids with outstanding efficacy and potency as AChE inhibitors, the
      mechanistic, their safety profiles, and pharmacokinetic attributes have been
      discussed. Through derivatization of these reported flavonoids, some limitation
      in efficacy or pharmacokinetic parameters can be addressed. The selected
      flavonoids ought to be tested in clinical studies to discover new neuro
      therapeutic candidates.

PMID- 29635896
TI  - Helix aspersa maxima mucus exhibits antimelanogenic and antitumoral effects
      against melanoma cells.
AB  - Snail secretion is currently revolutionizing the world of cosmetics and human
      skin care. The efficacy of snail secretion in wounds healing has been proven both
      in vitro and by clinical studies. However, the potential anti-tumor effect of
      snail secretion was poorly investigated. In this report, our in vitro study
      showed that Helix aspersa maxima species snail slime (SS) could not only treat
      melanogenesis but also endowed with anti-tumoral activity against human melanoma
      cells. Indeed, SS reduced melanin content and tyrosinase activity on B16F10 cells
      with IC50 values of 288 MUg/mL and 286 MUg/mL, respectively, without altering
      cell viability. This effect was also observed, at a lesser extent, on human
      melanoma IGR-39 and SK-MEL-28 cell lines. On another hand, SS specifically
      inhibited the viability of IGR-39 and SK-MEL-28 cells associated to an apoptotic
      effect highlighted by PARP cleavage. It is worth to note that SS did not affect
      the viability of B16F10 cells and non tumorigenic HaCaT cells. Interestingly,
      this extract was found to inhibit migration and invasion of both human melanoma
      cells through reducing the expression of Matrix metalloproteinase MMP2. Snail
      slime also exerted a high inhibitory effect on IGR-39 cell adhesion through
      blocking the function of alpha2beta1 (45%), alphavbeta3 (38%) integrins and by
      reducing the expression levels of alphav and beta1 integrins. The presented
      results shed light on the potential anti-melanoma effect of SS and support its
      use against skin diseases.

PMID- 29635897
TI  - Immunomodulatory activity of polysaccharide from Helicteres angustifolia L. on
      4T1 tumor-bearing mice.
AB  - To evaluate the in vivo immunomodulatory activity of the crude polysaccharide
      from Helicteres angustifolia L. (HACP), a 4T1 breast tumor model in BALB/c mice
      was used in this study. After tumor incubation for 6 days, mice were orally
      administered with 100, 200, and 300 mg/kg of HACP for 15 days. The results show
      that HACP administration resulted in a remarkable immunomodulatory effect
      attributable to the increased spleen and thymus indices, unregulated CD4+/CD8+
      ratios in spleen lymphocytes, and the augmentation of IL-1beta, IFN-gamma, and
      TNF-alpha productions in the serum of tumor-bearing mice. The increased immunity
      resulted in a significant reduction in the tumor weight in 100, 200, and 300
      mg/kg of HACP treatment groups, achieving inhibition rates of 34.58 +/- 10.20%,
      57.80 +/- 8.65% and 67.71 +/- 5.80%, respectively. In addition, a reduced lung
      metastasis was also detected in the HACP treatment groups. These findings, for
      the first time, provide scientific evidence that HACP can improve the immune
      response in 4T1 tumor-bearing mice, which plays a major role in the antitumor
      effect. Thus, HACP is prospectively valuable to be developed as new products with
      immunomodulatory activity and used for the treatment of breast cancer.

PMID- 29635898
TI  - Heme oxygenase byproducts variably influences myocardial and autonomic
      dysfunctions induced by the cyclosporine/diclofenac regimen in female rats.
AB  - We recently reported that exposure to cyclosporine (CSA) plus diclofenac causes
      hypertension and impairs left ventricular (LV) and cardiac autonomic functions in
      female rats. Here, we tested the hypothesis that these effects could be mitigated
      by facilitated heme oxygenase (HO) signaling. Experiments were performed in
      female rats to assess the effects of 10-day treatment with CSA (25
      mg/kg/day)/diclofenac (1 mg/kg/day) regimen on cardiovascular functions in
      absence and presence of maneuvers that upregulate HO or its enzymatic products.
      The CSA/diclofenac-induced hypertension and impairment in cardiac sympathovagal
      balance (i.e. reduced low-frequency/high-frequency spectral ratio) were blunted
      upon concurrent treatment with hemin (HO-1 inducer), tricarbonyldichlororuthenium
      (II) dimer (CORM-2, carbon monoxide-releasing molecule), or bilirubin. While none
      of the latter treatments affected the CSA/diclofenac-evoked decrease in
      isovolumic relaxation constant (Tau, a measure of diastolic function), the
      increased LV contractility (dP/dtmax) and attenuated reflex bradycardia in
      CSA/diclofenac-treated rats was abolished by bilirubin only. Paradoxically, the
      CSA/diclofenac-evoked attenuation in reflex tachycardia was improved in presence
      of hemin or CORM-2, but not bilirubin. The favorable hemin effects were abrogated
      after inhibition of HO (ZnPP) or nitric oxide synthase (NOS, l-NAME). These
      finding highlights NOS-dependent modulatory roles for HO and its enzymatic
      products in improving the worsened cardiovascular profile in CSA/diclofenac
      treated female rats.

PMID- 29635899
TI  - The effects of Ciji-Hua'ai-Baosheng on immune function of mice with H22
      hepatocellular carcinoma receiving chemotherapy.
AB  - BACKGROUND: Ciji-Hua'ai-Baosheng Decoction (CHBD) is a traditional Chinese
      formula that may attenuate the toxicity and side-effects of chemotherapy. The
      formula may also prolong the life of cancer patients. Whether CHBD should be
      employed as adjunctive therapy for cancer patients receiving chemotherapy has yet
      to be determined as does the mechanism whereby CHBD exerts its beneficial
      effects. AIM OF THE STUDY: To document the potential effects of CHBD on tumor
      growth and immune function in a murine model of hepatocellular carcinoma (HCC)
      receiving chemotherapy. MATERIALS AND METHODS: Sixty Kunming mice were injected
      subcutaneously with H22 hepatoma cells in the right anterior armpit. After seven
      days, the mice with formed tumors were injected with Cytoxan (CTX) (200 mg/kg) to
      establish the chemotherapy model. These mice were randomly divided into 5 groups:
      model (untreated controls), control (CTX,33.33 mg/kg), and high CHBD (H) (117
      g/kg), moderate CHBD (M) (58.5 g/kg) and low CHBD (L) (29.25 g/kg) treated
      groups. Tumor weights and inhibitory ratio (decrease in tumor dimensions),
      histology of tumor, colon, spleen and liver, and biochemical tests of liver and
      kidney function were documented after 10 days. Serum and tumor IL-2, IFN-gamma,
      IL-6, and TNF-alpha levels were determined by enzyme-linked immunosorbent assay
      (ELISA) and Western blot respectively. The potential bioactive compounds in CHBD
      were characterized by UHPLC-MS. RESULTS: Although tumor weights were decreased in
      CTX alone and CHBD (H) and CHBD (M) groups (-66%, -41% and -25% respectively),
      tumor cell density was reduced to the greatest extent in the CHBD (H) group. CHBD
      had no evident effects on liver and kidney function. CTX-induced colon
      inflammation and decrease in spleen lymphocytes were attenuated with CHBD
      treatment. CHBD increased serum IL-2, IFN-gamma and TNF-alpha, but decreased IL-6
      levels in serum and tumor tissue. UHPLC-MS analysis of CHBD revealed the presence
      of 11 bioactive compounds. CONCLUSIONS: In this murine model of HCC receiving
      chemotherapy, CHBD inhibited tumor growth, improved immune function and pro
      inflammatory cytokine responses while attenuating CTX-associated side effects.

PMID- 29635900
TI  - Pharmacological inhibition of TRPV4 channel suppresses malignant biological
      behavior of hepatocellular carcinoma via modulation of ERK signaling pathway.
AB  - TRPV4 (transient receptor potential vanilloid 4), a member of the TRP
      superfamily, has been reported to correlate with several different forms of
      cancers. However, the role of TRPV4 in human hepatocellular carcinoma (HCC)
      remains unclear. The present study demonstrated that elevated expression of TRPV4
      was shown in HCC tumor tissues when compared with paired non-tumoral livers both
      in protein and mRNA levels. Furthermore, the enhanced expression of TRPV4 was
      highly associated with histological grade (P = 0.036) and the number of tumors (P
      = 0.045). Pharmacological inhibition of TRPV4 channels in HCC cells with the
      specific antagonist HC-067047 suppressed cell proliferation, induced apoptosis
      and decreased the migration capability by attenuating the epithelial-mesenchymal
      transition (EMT) process in vitro. The p-ERK expression was apparently repressed
      after treatment with the TRPV4 antagonist, further blockade of the ERK pathway
      with U0126 could significantly aggravate HCC cells apoptosis. In NOD-SCID mouse
      xenograft models, intraperitoneal injection of HC-067047 could obviously suppress
      tumor growth and induce apoptosis in vivo. Together, our studies showed that the
      antitumor effects caused by TRPV4 channel inhibition in HCC cell lines might be
      attributed to the suppression of EMT process and inactivation of p-ERK which
      induced subsequent cell apoptosis. Thus, pharmacological inhibition of TRPV4
      channel may be an option for HCC treatment.

PMID- 29635901
TI  - Subacute ghrelin administration inhibits apoptosis and improves ultrastructural
      abnormalities in remote myocardium post-myocardial infarction.
AB  - This study investigated the effect of ghrelin on cardiomyocytes function,
      apoptosis and ultra-structural alterations of remote myocardium of the left
      ventricle (LV) of rats, 21 days post myocardial infarction (MI). Rats were
      divided into 4 groups as a control, a sham-operated rats, a sham
      operated+ghrelin, an MI + vehicle and an MI + ghrelin-treated rats. MI was
      induced by LAD ligation and then rats were recievd a concomitant doe of either
      normal saline as a vehicle or treated with ghrelin (100 MUg/kg S.C., 2x/day) for
      21 consecutive days. Ghrelin enhanced myocardial contractility in control rats
      and reversed the decreases in myocardial contractility and the increases in the
      serum levels of CK-MB and LDH in MI-induced rats. Additionally, it inhibited the
      increases in levels of Bax and cleaved caspase 3 and increased those for Bcl-2 in
      the remote myocardium of rat's LV, post-MI. At ultra-structural level, while
      ghrelin has no adverse effects on LV myocardium obtained from control or sham
      treated rats, ghrelin post-administration to MI-induced rats reduced vascular
      formation, restored normal microfilaments appearance and organization, preserved
      mitochondria structure, and prevented mitochondrial swelling, collagen deposition
      and number of ghost bodies in the remote areas of their LV. Concomitantly, in
      remote myocardium of MI-induced rats, ghrelin enhanced endoplasmic reticulum
      intracellular organelles count, decreased number of atrophied nuclei and
      phagocytes, diminished the irregularity in the nuclear membranes and inhibited
      chromatin condensation. In conclusion, in addition to the physiological,
      biochemical and molecular evidence provided, this is the first study that
      confirms the anti-apoptotic effect of ghrelin in the remote myocardium of the LV
      during late MI at the level of ultra-structural changes.

PMID- 29635902
TI  - New therapeutics from Nature: The odd case of the bacterial cytotoxic necrotizing
      factor 1.
AB  - Natural products may represent a rich source of new drugs. The enthusiasm toward
      this topic has recently been fueled by the 2015 Nobel Prize in Physiology or
      Medicine, awarded for the discovery of avermectin and artemisinin, natural
      products from Bacteria and Plantae, respectively, which have targeted one of the
      major global health issues, the parasitic diseases. Specifically, bacteria either
      living in the environment or colonizing our body may produce compounds of
      unexpected biomedical value with the potentiality to be employed as therapeutic
      drugs. In this review, the fascinating history of CNF1, a protein toxin produced
      by pathogenic strains of Escherichia coli, is divulged. Even if produced by
      bacteria responsible for a variety of diseases, CNF1 can behave as a promising
      benefactor to mankind. By modulating the Rho GTPases, this bacterial product
      plays a key role in organizing the actin cytoskeleton, enhancing synaptic
      plasticity and brain energy level, rescuing cognitive deficits, reducing glioma
      growth in experimental animals. These abilities strongly suggest the need to
      proceed with the studies on this odd drug in order to pave the way toward
      clinical trials.

PMID- 29635903
TI  - The dialyzable leukocyte extract TransferonTM inhibits tumor growth and brain
      metastasis in a murine model of prostate cancer.
AB  - Prostate cancer (PCa) is the second most frequently diagnosed cancer in men
      worldwide. Dialyzed Leukocyte Extracts (DLEs) are heterogeneous mixtures of low
      molecular-weight peptides that improve clinical responses in various diseases.
      Here, we analyzed the effects of TransferonTM, a commercial DLE with
      characterized active pharmaceutical ingredient and proven batch-to-batch
      reproducibility, in preclinical models of PCa. We employed v-Src-transformed
      murine prostate epithelial (PEC-Src) cells, which recapitulate the
      transcriptional profiles in human PCa, can be grown in immunocompetent mice, and
      consistently form bone and brain metastases. In vitro, TransferonTM did not
      induce cytotoxicity nor alterations in migration /invasion of PEC-Src cells. In
      vivo, TransferonTM reduced metastatic dissemination after intracardiac injection
      of PEC-Src and inhibited tumor growth of subcutaneous isotransplants. The
      antineoplastic effect of TransferonTM correlated with changes in tumor
      infiltration, increased serum concentrations of IL-12 and CXCL1, and reduced
      levels of VEGF. Our results suggest that the antineoplastic effect produced by
      TransferonTM is due to its immunomodulatory activity and not by a direct effect
      on cancer cells, and indicate that TransferonTM could be beneficial as adjuvant
      therapy in PCa patients.

PMID- 29635904
TI  - GDPD5, a target of miR-195-5p, is associated with metastasis and chemoresistance
      in colorectal cancer.
AB  - PURPOSE: Successful treatment of colorectal cancer (CRC) is greatly impeded by
      metastasis and chemoresistance, particularly to 5-fluoruracil (5-Fu), one of the
      staples of clinical intervention in advanced CRC. The purpose of this study is to
      determine whether the gene glycerophosphodiester phosphodiesterase domain
      containing 5 (GDPD5) contributes to CRC cell metastasis and 5-Fu resistance.
      Ultimately, we evaluated the ability of microRNA 195-5p (miR-195-5p) to reduce
      GDPD5 expression and thus to enhance CRC cell susceptibility to chemotherapy.
      METHODS: We obtained human primary CRC and adjacent normal tissues from 15
      patients who underwent CRC resection. Quantitative real-time polymerase chain
      reactions (qRT-PCR), western blot, and immunohistochemistry (IHC) were used to
      determine GDPD5 expression levels in the human CRC tissues, four CRC cell lines,
      and two 5-Fu resistant CRC cell lines. To measure the impact of GDPD5 on CRC cell
      chemoresistance, we silenced GDPD5 using GDPD5 siRNA and measured cell survival
      and apoptosis using MTT assays and TUNEL staining, respectively. Transwell
      Matrigel invasion assays were performed to explore whether GDPD5 affects the
      invasion capabilities of 5-Fu resistant CRC cells. Finally, to assess the effects
      of miR-195-5p on GDPD5 levels and CRC cell chemoresistance, we generated
      luciferase reporter plasmids with either the wild-type 3'UTR miR-195-5p potential
      binding sites or mutant binding sites of GDPD5. RESULTS: We first determined that
      GDPD5 mRNA and protein are overexpressed in human primary CRC tissues as compared
      to adjacent normal tissues. GDPD5 overexpression was also evident in four CRC
      cell lines (Caco-2, HCT8, HCT116 and SW480), as well as in the two 5-Fu resistant
      CRC cell lines that we generated (HCT116/5-Fu and SW480/5-Fu). Using MTT assays
      and TUNEL staining of HCT116/5-Fu and SW480/5-Fu cells, we found that GDPD5
      silencing sensitizes 5-Fu resistant CRC cells to 5-Fu. Furthermore, GDPD5
      silencing in 5-Fu resistant CRC cells reduced the epithelial-to-mesenchymal
      transition (EMT) and cell invasion, both of which are crucial for CRC metastasis.
      We then used the bioinformatics algorithm TargetScan to identify the miRNA miR
      195-5p, which targets two regions of GDPD5 3'UTR. By generating luciferase
      reporter plasmids with the 3'UTR miR-195-5p binding sites, we ultimately
      determined that miR-195-5p increases chemosensitivity and cell apoptosis in 5-Fu
      resistant CRC cells. CONCLUSION: This study identifies the gene GDPD5 as an
      effector of chemoresistance and metastasis in CRC. Furthermore, our results
      demonstrate that miR-195-5p is a potent suppressor of GDPD5 and that, as such, it
      significantly increases chemosensitivity and apoptosis in chemoresistant CRC
      cells. This study thus not only identifies potential prognostic biomarkers of
      CRC, but it also opens the possibility for incorporating miR-195-5p into current
      therapeutic regimens to overcome barriers to successful CRC treatment.

PMID- 29635905
TI  - Protective roles and mechanisms of polysaccharides from Dendrobium officinal on
      natural aging-induced premature ovarian failure.
AB  - This study was designed to investigate the pharmacological effects and mechanisms
      of polysaccharides from Dendrobium officinal (DOP) on premature ovarian failure
      (POF) in natural aging mice. Fifteen months old female mice (n  =  28) and young
      adult female mice (n  =  14, 6 weeks) were used. DOP (70 mg/kg) was administrated
      to mice by oral gavage for 10 weeks and the protection effects of DOP on ovaries
      were investigated in vivo. The results showed that DOP reduced body weight, ovary
      and uterus/body weight parameters to normal level and alleviated ovarian
      pathological damage. Moreover, DOP could reduce pro-inflammatory cytokines (TNF
      alpha, IL-6) and MDA levels and improve estradiol, SOD, GSH-Px, T-AOC and IL-10
      levels in serum. These results suggested that DOP may alleviate the damage caused
      by aging through the inhibition of the nuclear factor -kappaB (NF-kappaB) and
      p53/Bcl-2-mediate signaling pathways. Moreover, we found that DOP can increase
      the numbers of mitochondria and endoplasmic reticulum. Moreover, DOP increased
      the numbers of different stages of follicular cells and improved mitochondrial
      membrane potential in ovaries. These results indicated that DOP may relieve
      ovarian damage through the protection of mitochondria in the ovaries. These
      findings suggest that DOP may be a promising drug for treating POF caused by
      natural aging in females.

PMID- 29635906
TI  - Diterpenoid trigonoreidon B isolated from Trigonostemon reidioides alleviates
      inflammation in models of LPS-stimulated murine macrophages and inflammatory
      liver injury in mice.
AB  - The roots of Trigonostemon reidioides, Thai medicinal plant, have long been used
      as an antidote, laxative, and antiasthmatic, and also used as folk remedy for
      relieving inflammatory symptoms from poisonous insect and snake bites as well as
      abscesses and sprains. Here, we studied anti-inflammatory effects of a major
      diterpenoid named trigonoreidon B (TR-B) isolated from T. reidioides roots in
      lipopolysaccharide (LPS)-activated RAW264.7 macrophages and D-galactosamine (D
      GalN)/LPS-induced inflammatory liver injury in mice. RAW264.7 cells were treated
      with TR-B or other available minor diterpenoids, and cell viability was
      determined by AlamarBlue. The levels of inflammatory mediators were determined by
      nitrite assay, ELISA, and luminescence. NF-kappaB nuclear translocation was
      investigated by indirect immunofluorescence. Expression levels were determined by
      real-time PCR and Western blotting. Transaminases and caspase activities were
      determined by using assay kits. Our results showed that TR-B was able to suppress
      PI3K/Akt activation and inflammatory induction in LPS-activated macrophages.
      These events were concomitant with TR-B's ability to hamper activated generation
      of reactive oxygen species, nitric oxide, prostaglandin E2, and cytokines as well
      as NF-kappaB p65 nuclear translocation. In an in vivo model of inflammatory liver
      injury, an administration of TR-B protected mice from D-GalN/LPS-induced liver
      injury by suppressing the elevation of serum TNF-alpha, transaminase activities,
      and hepatocyte apoptosis as well as an improvement of liver histopathology.
      During protection against liver damage, TR-B also prevented the loss of Akt
      phosphorylation. Collectively, the results of this present study suggested that
      TR-B exerted an anti-inflammatory effect via attenuating macrophage-mediated
      inflammation and inflammatory liver injury in vivo. TR-B may represent a
      promising lead compound for anti-inflammatory drug development.

PMID- 29635907
TI  - Ameliorative effect of ursolic acid on renal fibrosis in adenine-induced chronic
      kidney disease in rats.
AB  - Ursolic acid (UA), an ursane-type pentacyclic triterpenoid commonly found in
      apple peels and holy basil has been shown to possess many beneficial effects.
      Renal fibrosis is a complication of kidney injury and associated with increased
      risk of morbidity and mortality. In our previous investigation, a lupane-type
      pentacyclic triterpenoid, betulinic acid (BA) was found to have protective effect
      on chronic kidney disease (CKD) and renal fibrosis. This prompted us to explore
      the therapeutic value of UA, a chemically related compound to BA in CKD. CKD was
      induced by feeding adenine with the feed at a concentration of 0.75% for 28 days.
      UA at the dose rate of 30 mg/kg in 0.5% carboxy methyl cellulose (CMC) was
      administered by oral route, simultaneously with adenine feeding for 28 days.
      Adenine feeding increased the kidney weight to body weight index, decreased the
      kidney function due to injury as indicated by increased markers like serum urea,
      uric acid, creatinine, cystatin C and neutrophil gelatinase-associated lipocalin
      (NGAL) and initiated the fibrotic response in kidney by increasing the
      profibrotic proteins viz. transforming growth factor-beta (TGF-beta), connective
      tissue growth factor (CTGF), fibronectin and collagen. However, treatment with UA
      reversed the damage induced by adenine as shown by reduced kidney injury and
      fibrosis markers which was further clearly evident in histological picture
      indicating the suitability of UA for use in CKD.

PMID- 29635908
TI  - Possible mechanisms of prednisolone-induced osteoporosis in zebrafish larva.
AB  - Glucocorticoid-induced osteoporosis (GIOP) is a serious clinical bone disease
      that results from the long-term consumption of glucocorticoids or glucocorticoid
      like drugs. Although many studies have attempted to determine the mechanisms of
      GIOP, they are still unclear. In this study, we established a zebrafish model of
      glucocorticoid-like drug-induced osteoporosis by treating larvae with
      prednisolone. We then quantified the expression of a selection of extracellular
      matrix (ECM)-, osteoblast-, and osteoclast-related genes. Our results showed that
      at 15 days post fertilization, zebrafish larvae treated with 25 MUM prednisolone
      are a suitable model for GIOP, not only owing to the decrease in robust bone mass
      but also because of significant alterations in gene expression. The
      quantification of the expression of ECM-, osteoblast-, and osteoclast- related
      genes revealed that mmp9 and mmp13 were significantly upregulated and entpd5a,
      acp5a, and sost were significantly downregulated. These genes may be a target for
      future research into GIOP. Our study thus provides new insights into GIOP.

PMID- 29635909
TI  - Porphyromonas gingivalis lipopolysaccharide-induced macrophages modulate
      proliferation and invasion of head and neck cancer cell lines.
AB  - AIM: The aim of this study was to investigate the effect of Porphyromonas
      gingivalis lipopolysaccharide (LPS)-induced macrophages on head and neck squamous
      cell carcinoma (HNSCC) cell line proliferation and invasion. MAIN METHODS: THP-1
      monocytes were differentiated toward macrophages using 12.5 ng/ml phorbol 12
      myristate 13-acetate treatment for 48 h. The expression of interleukin-6 (IL-6)
      mRNA and cytokine by monocytes and macrophages was determined using real time PCR
      and ELISA, respectively. The cells were analyzed for CD14 expression using
      immunofluorescent labeling. The macrophages were induced using 1 MUg/ml P.
      gingivalis LPS for 24 h, and the conditioned medium (CM) was collected. The
      monocyte, macrophage, and LPS-induced macrophage CM were evaluated for IL-6 and
      tumor necrosis factor-alpha (TNF-alpha), and nitric oxide (NO) content using
      ELISA and the Griess Reagent System, respectively. Human primary (HN18, HN30, and
      HN4) and metastatic (HN17, HN31, and HN12) HNSCC cell lines were treated with the
      monocyte, macrophage, and LPS-induced macrophage CM. The proliferation and
      invasion of the HNSCC cell lines were evaluated using MTT and modified Boyden
      chamber assays, respectively. KEY FINDINGS: Macrophages demonstrated increased IL
      6 and CD14 expression. The P. gingivalis LPS significantly induced macrophage NO
      secretion, however, that of TNF-alpha decreased. The LPS-induced macrophages CM
      inhibited HN4 proliferation. Interestingly, the LPS-induced macrophage CM
      promoted invasion of all HNSCC cell lines. SIGNIFICANCE: Our data demonstrate
      that P. gingivalis LPS-induced macrophages increased NO secretion. The activated
      macrophage CM inhibited HN4 cell proliferation and promoted invasion of all HNSCC
      cell lines.

PMID- 29635910
TI  - Process evaluation and in vitro selectivity analysis of aptamer-drug polymeric
      formulation for targeted pharmaceutical delivery.
AB  - Targeted drug delivery is a promising strategy to promote effective delivery of
      conventional and emerging pharmaceuticals. The emergence of aptamers as superior
      targeting ligands to direct active drug molecules specifically to desired
      malignant cells has created new opportunities to enhance disease therapies. The
      application of biodegradable polymers as delivery carriers to develop aptamer
      navigated drug delivery system is a promising approach to effectively deliver
      desired drug dosages to target cells. This study reports the development of a
      layer-by-layer aptamer-mediated drug delivery system (DPAP) via a w/o/w double
      emulsion technique homogenized by ultrasonication or magnetic stirring.
      Experimental results showed no significant differences in the biophysical
      characteristics of DPAP nanoparticles generated using the two homogenization
      techniques. The DPAP formulation demonstrated a strong targeting performance and
      selectivity towards its target receptor molecules in the presence of non-targets.
      The DPAP formulation demonstrated a controlled and sustained drug release profile
      under the conditions of pH 7 and temperature 37  degrees C. Also, the drug
      release rate of DPAP formulation was successfully accelerated under an endosomal
      acidic condition of ~pH 5.5, indicating the potential to enhance drug delivery
      within the endosomal micro-environment. The findings from this work are useful to
      understanding polymer-aptamer-drug relationship and their impact on developing
      effective targeted delivery systems.

PMID- 29635912
TI  - Directional Building Blocks Determine Linear and Cyclic Silicon Architectures.
AB  - Silicon nanomaterials combine earth abundance and biodegradability with
      exceptional electronic properties. Strategic synthesis promises access to novel
      architectures with well-defined surface structure, size, and shape. Herein, we
      describe a five-step synthesis of functional macrocyclic polysilanes. Comparison
      of the materials isolated from isomeric building blocks provides evidence that
      building block directionality controls the shape of the resulting nanomaterial.
      Infrared (IR) and 1H and 29Si NMR spectroscopies, coupled to computational data,
      provide evidence of a well-defined Si-H and Si-Me terminated structure. The
      intrinsic porosity and the polarization arising from the hydridic character of
      the Si-H bond suggest applications in lithium-ion batteries, which are supported
      by quantum chemical calculations.

PMID- 29635911
TI  - Neural Stem Cell Differentiation Using Microfluidic Device-Generated Growth
      Factor Gradient.
AB  - Neural stem cells (NSCs) have the ability to self-renew and differentiate into
      multiple nervous system cell types. During embryonic development, the
      concentrations of soluble biological molecules have a critical role in
      controlling cell proliferation, migration, differentiation and apoptosis. In an
      effort to find optimal culture conditions for the generation of desired cell
      types in vitro, we used a microfluidic chip-generated growth factor gradient
      system. In the current study, NSCs in the microfluidic device remained healthy
      during the entire period of cell culture, and proliferated and differentiated in
      response to the concentration gradient of growth factors (epithermal growth
      factor and basic fibroblast growth factor). We also showed that overexpression of
      ASCL1 in NSCs increased neuronal differentiation depending on the concentration
      gradient of growth factors generated in the microfluidic gradient chip. The
      microfluidic system allowed us to study concentration-dependent effects of growth
      factors within a single device, while a traditional system requires multiple
      independent cultures using fixed growth factor concentrations. Our study suggests
      that the microfluidic gradient-generating chip is a powerful tool for determining
      the optimal culture conditions.

PMID- 29635913
TI  - Bioluminescence Imaging of Carbon Monoxide in Living Cells and Nude Mice Based on
      Pd0-Mediated Tsuji-Trost Reaction.
AB  - Carbon monoxide (CO) is highly toxic and lethal to humans and animals because of
      its strong affinity for hemoglobin, while this "silent killer" is constantly
      generated in the body as a cell-signaling molecule of the gasotransmitter family
      in various pathological and physiological conditions. Up to now, designing
      fluorescent probes for real-time imaging of CO in living species is a continuous
      challenge due to background interference, light scattering, and
      photoactivation/photobleaching. Herein, a novel type of bioluminescence probe
      (allyl-luciferin) was synthesized and exploited to realize CO imaging with high
      signal-to-noise ratios. Based on Pd0-mediated Tsuji-Trost reaction, allyl
      luciferin specifically reacted with CO to yield D-luciferin and thus generate a
      turn-on bioluminescence response, exhibiting high selectivity against bioactive
      small molecules such as reactive nitrogen, oxygen, and sulfur species.
      Furthermore, the new probe can be easily employed to detect exogenous CO in Huh7
      cells and MDA-MB-231 cells, and CO production was enhanced greatly in these
      living cells after pretreatment with [Ru(CO)3Cl-(glycinate)] (CORM-3). Through
      the use of PdCl2-containing liposomes to improve poor membrane permeability of
      PdCl2, endogenous CO stimulated by heme was also seen clearly. In addition, the
      probe was successfully used to monitor exogenous and endogenous CO in nude mice.
      Overall, our data proved that the allyl-luciferin is a promising tool for
      exogenous and endogenous CO detection and imaging within living species. This is
      the first demonstration of bioluminescence imaging obtained by a probe for CO. We
      anticipate that the good imaging properties of allyl-luciferin presented in this
      study will provide a potentially powerful approach for illuminating CO functions
      in the future.

PMID- 29635914
TI  - Electrical Transport Signature of the Magnetic Fluctuation-Structure Relation in
      alpha-RuCl3 Nanoflakes.
AB  - The small gap semiconductor alpha-RuCl3 has emerged as a promising candidate for
      quantum spin liquid materials. Thus far, Raman spectroscopy, neutron scattering,
      and magnetization measurements have provided valuable hints for collective spin
      behavior in alpha-RuCl3 bulk crystals. However, the goal of implementing alpha
      RuCl3 into spintronic devices would strongly benefit from the possibility of
      electrically probing these phenomena. To address this, we first investigated
      nanoflakes of alpha-RuCl3 by Raman spectroscopy and observed similar behavior as
      in the case of the bulk material, including the signatures of possible
      fractionalized excitations. In complementary experiments, we investigated the
      electrical charge transport properties of individual alpha-RuCl3 nanoflakes in
      the temperature range between 120 and 290 K. The observed temperature-dependent
      electrical resistivity is consistent with variable range hopping behavior and
      exhibits a transition at about 180 K, close to the onset temperature observed in
      our Raman measurements. In conjunction with the established relation between
      structure and magnetism in the bulk, we interpret this transition to coincide
      with the emergence of fractionalized excitations due to the Kitaev interactions
      in the nanoflakes. Compared to the bulk samples, the transition temperature of
      the underlying structural change is larger in the nanoflakes. This difference is
      tentatively attributed to the dimensionality of the nanoflakes as well as the
      formation of stacking faults during mechanical exfoliation. The demonstrated
      devices open up novel perspectives toward manipulating the Kitaev-phase in alpha
      RuCl3 via electrical means.

PMID- 29635915
TI  - Three-Dimensional Hierarchical Framework Assembled by Cobblestone-Like CoSe2@C
      Nanospheres for Ultrastable Sodium-Ion Storage.
AB  - Sodium-ion batteries (SIBs), as the promising commercial energy system, are
      restricted by their sluggish kinetics and low sodium-ion storage. Metal selenide
      possesses good conductivity and capacity but still suffers from the stacked
      problem and volume expansion. Significantly, CoSe2/C is successfully prepared
      with the assistance of citric acid as both a chelating agent and carbon
      precursor, displaying that cobblestone-like nanospheres with the radii (<25 nm)
      distribute uniformly in the carbon matrix. It is expected that the established Co
      O-C bonds enhance the stability of the structure with faster ion shuttling. With
      the available electrolyte (NaCF3SO3/diethylene glycol dimethyl ether) in a
      potential window range from 0.5 to 3.0 V, the as-obtained sample shows the
      ultralong lifespan at 4.5 A g-1, retaining a capacity of 345 mA h g-1 after 10
      000 cycles. From the detailed kinetic analysis, it is clear that the surface
      controlled electrochemical behavior mainly contributes to the excellent large
      current cycling stability and Na storage capacity. The ex situ results support
      that the crystal and morphological structure remains stable. This work is
      anticipated to enhance the in-depth understanding of the CoSe2/C anode and supply
      a facile manner to obtain electrode materials for SIBs.

PMID- 29635916
TI  - Proteome-Wide Evaluation of Two Common Protein Quantification Methods.
AB  - Proteomics experiments commonly aim to estimate and detect differential abundance
      across all expressed proteins. Within this experimental design, some of the most
      challenging measurements are small fold changes for lower abundance proteins.
      While bottom-up proteomics methods are approaching comprehensive coverage of even
      complex eukaryotic proteomes, failing to reliably quantify lower abundance
      proteins can limit the precision and reach of experiments to much less than the
      identified-let alone total-proteome. Here we test the ability of two common
      methods, a tandem mass tagging (TMT) method and a label-free quantitation method
      (LFQ), to achieve comprehensive quantitative coverage by benchmarking their
      capacity to measure 3 different levels of change (3-, 2-, and 1.5-fold) across an
      entire data set. Both methods achieved comparably accurate estimates for all 3
      fold-changes. However, the TMT method detected changes that reached statistical
      significance three times more often due to higher precision and fewer missing
      values. These findings highlight the importance of refining proteome quantitation
      methods to bring the number of usefully quantified proteins into closer agreement
      with the number of total quantified proteins.

PMID- 29635919
TI  - Natural Product Total Synthesis: As Exciting as Ever and Here To Stay.

PMID- 29635917
TI  - Development of a PEGylated-Based Platform for Efficient Delivery of Dietary
      Antioxidants Across the Blood-Brain Barrier.
AB  - The uptake and transport of dietary antioxidants remains the most important
      setback for their application in therapy. To overcome the limitations, a
      PEGylated-based platform was developed to improve the delivery properties of two
      dietary hydroxycinnamic (HCA) antioxidants-caffeic and ferulic acids. The
      antioxidant properties of the new polymer-antioxidant conjugates (PEGAntiOxs),
      prepared by linking poly(ethylene glycol) (PEG) to the cinnamic acids by a one
      step Knovenagel condensation reaction, were evaluated. PEGAntiOxs present a
      higher lipophilicity than the parent compounds (caffeic and ferulic acids) and
      similar, or higher, antioxidant properties. PEGAntiOxs were not cytotoxic at the
      tested concentrations in SH-SY5Y, Caco-2, and hCMEC/D3 cells. By contrast,
      cytotoxic effects in hCMEC/D3 and SH-SY5Y cells were observed, at 50 and 100 MUM,
      for caffeic and ferulic acids. PEGAntiOxs operate as antioxidants against several
      oxidative stress-cellular inducers in a neuronal cell-based model, and were able
      to inhibit glycoprotein-P in Caco-2 cells. PEGAntiOxs can cross hCMEC/D3
      monolayer cells, a model of the blood-brain barrier (BBB) endothelial membrane.
      In summary, PEGAntiOxs are valid antioxidant prototypes that can uphold the
      antioxidant properties of HCAs, reduce their cytotoxicity, and improve their BBB
      permeability. PEGAntiOxs can be used in the near future as drug candidates to
      prevent or slow oxidative stress associated with neurodegenerative diseases.

PMID- 29635920
TI  - Additive Manufacturing of Nano- and Microarchitected Materials.

PMID- 29635921
TI  - Negative Correlation of Serum Adiponectin Levels With Carotid-Femoral Pulse Wave
      Velocity in Patients Treated With Hemodialysis.
AB  - PURPOSE: The aim of this study was to evaluate the relationship between serum
      adiponectin levels and carotid-femoral pulse wave velocity (cfPWV) in
      hemodialysis (HD) patients. METHOD: Blood samples were obtained from 120 HD
      patients. cfPWV was measured with a validated tonometry system (SphygmoCor; AtCor
      Medical, West Ryde, Australia). Serum adiponectin levels were measured using a
      commercially available enzyme-linked immunosorbent assay kit. RESULTS: By
      univariate linear analysis of cfPWV in HD patients, we found that diabetes ( r =
      .281, p = .002), pre-HD body weight ( r = .194, p = .033), post-HD body weight (
      r = .192, p = .036), waist circumference ( r =.210, p = .022), and body fat mass
      ( r = .194, p = .034) were positively correlated, whereas adiponectin level ( r =
      -.254, p = .005) was negatively correlated with cfPWV in HD patients.
      Multivariate forward stepwise linear regression analysis showed that diabetes
      (beta = .274, p = .006) and adiponectin level (beta = -.215, p = .016) were
      independent predictors of cfPWV in HD patients. Moreover, post-HD body weight
      (beta = -.274, p = .041), waist circumference (beta = -.311, p < .001),
      logarithmically transformed triglyceride level (log-TG; beta = -.186, p = .031),
      and log-glucose (beta = -.225, p = .008) were negatively associated with
      adiponectin levels in HD patients after multivariable forward stepwise linear
      regression analysis. CONCLUSIONS: Among HD patients, serum adiponectin level was
      inversely associated with cfPWV level, and post-HD body weight, waist
      circumference, log-TG, and log-glucose were negatively associated with
      adiponectin level.

PMID- 29635922
TI  - Driving with Parkinson's disease: Cut points for clinical predictors of on-road
      outcomes: La conduite automobile et la maladie de Parkinson : Points de decoupage
      pour les predicteurs clinique des resultats des epreuves sur route.
AB  - BACKGROUND: Parkinson's disease (PD) is a common neurodegenerative disorder that
      impacts a person's fitness to drive. Practitioners require a sensitive and
      predictive battery of clinical tests to identify at-risk drivers. PURPOSE: This
      study aimed to identify clinical predictors and their optimal cut points,
      sensitivity, specificity, and predictive values of on-road outcomes in drivers
      with PD. METHOD: Participants ( N = 101) underwent a comprehensive driving
      evaluation. We identified predictors of pass/fail outcomes through logistic
      regression and computed optimal cut points through receiver operating
      characteristic curves and corresponding Youden indexes. FINDINGS: The Trail
      Making Test Part B (Trails B; sensitivity = .89, specificity = .74; positive
      predictive value [PPV] = .71; negative predictive value [NPV] = .91) and contrast
      sensitivity (sensitivity = .82, specificity = .63; PPV = .61; NPV = .84) emerged
      as significant predictors. The optimal cut point for the Trails B was 108 s (area
      under the curve = .86). IMPLICATIONS: Occupational therapists can benefit from
      implementing Trails B and contrast sensitivity screening as part of in-office
      screening of potentially at-risk drivers with PD.

PMID- 29635924
TI  - Corrigendum.

PMID- 29635923
TI  - Postfilter ionized calcium measurements in citrate anticoagulation for continuous
      renal replacement therapy: How often should Ca2+-membrane in blood gas analyser
      ABL800 be replaced?

PMID- 29635925
TI  - Effects of bismuth breast shielding on iodine quantification in dual-energy
      computed tomography: an experimental phantom study.
AB  - BACKGROUND: Although the bismuth breast shield can reduce radiation exposure to
      the breast during dual-energy computed tomography (DECT), it can potentially
      affect material quantification on DECT due to artifacts. PURPOSE: To evaluate the
      effects of bismuth breast shielding on iodine quantification and radiation
      exposure in DECT. MATERIAL AND METHODS: Small balloons were made with 0.2%, 0.6%
      and 1.0% blended iodinated contrast (370 mg/mL of iodine) with water. The
      balloons were located at both anterior and posterior lungs in an adult
      anthropomorphic chest phantom. DECT was performed with and without breast
      shielding. Afterwards, iodine concentration values were measured for each balloon
      on the iodine maps. Absorbed radiation doses in the breast were measured with the
      optically stimulated luminescence dosimeter. RESULTS: After shielding, we
      obtained significantly decreased iodine quantification for all three
      concentrations with 0.78 +/- 0.13 to 0.46 +/- 0.13 mg/mL, 2.31 +/- 0.17 to 1.68
      +/- 0.19 mg/mL, and 3.82 +/- 0.10 to 2.84 +/- 0.20 mg/mL at the anterior
      location, and 0.72 +/- 0.11 to 0.48 +/- 0.09 mg/mL, 2.24 +/- 0.13 to 1.87 +/-
      0.21 mg/mL, and 3.75 +/- 0.16 to 3.15 +/- 0.14 mg/mL at the posterior location
      for the 0.2%, 0.6%, and 1.0% balloons, respectively ( P = 0.001 for all). After
      shielding, absorbed radiation doses to the breast significantly decreased by
      14.8% (4.32 +/- 0.33 to 3.68 +/- 0.30 mGy; P = 0.005). CONCLUSION: Although using
      the bismuth breast shield may decrease radiation exposure to the breast on DECT,
      it may also significantly affect iodine quantification.

PMID- 29635926
TI  - Bacillus spp. as direct-fed microbial antibiotic alternatives to enhance growth,
      immunity, and gut health in poultry.
AB  - The increasing occurrence of antibiotic-resistant bacteria combined with
      regulatory pressure and consumer demands for foods produced without antibiotics
      has caused the agricultural industry to restrict its practice of using antibiotic
      growth promoters (AGP) in food animals. The poultry industry is not immune to
      this trend, and has been actively seeking natural alternatives to AGP that will
      improve the health and growth performance of commercial poultry flocks. Bacillus
      probiotics have been gaining in popularity in recent years as an AGP alternative
      because of their health-promoting benefits and ability to survive the harsh
      manufacturing conditions of chicken feed production. This review provides an
      overview of several modes of action of some Bacillus direct-fed microbials as
      probiotics. Among the benefits of these direct-fed microbials are their
      production of naturally synthesized antimicrobial peptides, gut flora modulation
      to promote beneficial microbiota along the gastrointestinal tract, and various
      immunological and gut morphological alterations. The modes of action for
      increased performance are not well defined, and growth promotion is not equal
      across all Bacillus species or within strains. Appropriate screening and
      characterization of Bacillus isolates prior to commercialization are necessary to
      maximize poultry growth to meet the ultimate goal of eliminating AGP usage in
      animal husbandry.

PMID- 29635927
TI  - Potential and limitations of health policy to improve coronary heart disease
      prevention and to reduce the burden of disease: A Russian experience.
AB  - Background Mortality from cardiovascular diseases is particularly high in Russia
      compared with the European average. The National Priority Project 'Health',
      launched in 2005, aimed to promote prevention of non-communicable diseases,
      particularly cardiovascular diseases, in primary care and to increase
      availability of state-of-art cardiovascular disease management. Methods This is a
      multiregional population based study with analysis of indicators for
      cardiovascular health and coronary heart disease in Moscow, St Petersburg, the
      Moscow region and across Russia, including a total population of 143.7 million
      inhabitants between 2005 and 2013. Data were collected using conventional
      methodology and originate from open statistical sources. Results The overall age
      standardized coronary heart disease mortality decreased in 2005-2013 by 24.7%
      from 383.6 to 289.0 per 100000 population, but with substantial interregional
      differences: it declined from 306.1 to 196.9 per 100,000 in Moscow (-35.7%), from
      362.1 to 258.9 per 100,000 in St Petersburg (-28.5%) and from 433.8 to 374.3 per
      100,000 in the Moscow region (-13.7%). Income in Moscow exceeded the national
      average 2-3-fold, and Moscow had the highest availability of modern treatments
      and interventions. Although vegetables, fruits and fish consumption increased
      overall in Russia, this trend was most prominent in Moscow. Indicators for
      psychosocial well-being also were best in Moscow. Life expectancy in Moscow is
      almost six years higher than the Russian average. Conclusion Health policy
      interventions turned out to be successful but with substantial interregional
      differences. Lower coronary heart disease mortality and higher life expectancy in
      Moscow may be due to a more favourable socioeconomic and psychological
      environment, more healthy eating and greater availability of medical care.

PMID- 29635928
TI  - The mystery further deepens: How much exercise is harmful for atrial
      fibrillation?

PMID- 29635929
TI  - "For Their Own Good": A Response to Popular Arguments Against Permitting Medical
      Assistance in Dying (MAID) where Mental Illness Is the Sole Underlying Condition.
AB  - Canada is approaching its federal government's review of whether patients should
      be eligible for medical assistance in dying (MAID) where mental illness is the
      sole underlying medical condition, and when "natural death" is not "reasonably
      foreseeable". For those opposed, arguments involve the following themes:
      capacity, value of life, vulnerability, stigma, irremediability, and the role of
      physicians. It has also been suggested that those who are able-bodied should have
      to kill themselves, even though suicide may be painful, lonely, and violent.
      Opponents of MAID for severe, refractory suffering due to mental illness imply
      that it is acceptable to remove agency from such patients on paternalistic
      grounds. After years of efforts to destigmatise mental illness, these kinds of
      arguments effectively declare all patients with mental illness, regardless of
      capacity, unable to make considered choices for themselves. The current paper
      argues that decisions about capacity must be made on an individual-patient basis.
      Given the rightful importance granted to respect for patient autonomy in liberal
      democracies, the wholesale removal of agency advocated by opponents of a
      permissive MAID regime is difficult to reconcile with Canadian constitutional
      values.

PMID- 29635930
TI  - Protein Promiscuity in H2O2 Signaling.
AB  - SIGNIFICANCE: Decrypting the cellular response to oxidative stress relies on a
      comprehensive understanding of the redox signaling pathways stimulated under
      oxidizing conditions. Redox signaling events can be divided into upstream sensing
      of oxidants, midstream redox signaling of protein function, and downstream
      transcriptional redox regulation. Recent Advances: A more and more accepted
      theory of hydrogen peroxide (H2O2) signaling is that of a thiol peroxidase redox
      relay, whereby protein thiols with low reactivity toward H2O2 are instead
      oxidized through an oxidative relay with thiol peroxidases. CRITICAL ISSUES:
      These ultrareactive thiol peroxidases are the upstream redox sensors, which form
      the first cellular port of call for H2O2. Not all redox-regulated interactions
      between thiol peroxidases and cellular proteins involve a transfer of oxidative
      equivalents, and the nature of redox signaling is further complicated through
      promiscuous functions of redox-regulated "moonlighting" proteins, of which the
      precise cellular role under oxidative stress can frequently be obscured by
      "polygamous" interactions. An ultimate goal of redox signaling is to initiate a
      rapid response, and in contrast to prokaryotic oxidant-responsive transcription
      factors, mammalian systems have developed redox signaling pathways, which
      intersect both with kinase-dependent activation of transcription factors, as well
      as direct oxidative regulation of transcription factors through peroxiredoxin
      (Prx) redox relays. FUTURE DIRECTIONS: We highlight that both transcriptional
      regulation and cell fate can be modulated either through oxidative regulation of
      kinase pathways, or through distinct redox-dependent associations involving
      either Prxs or redox-responsive moonlighting proteins with functional
      promiscuity. These protein associations form systems of crossregulatory networks
      with multiple nodes of potential oxidative regulation for H2O2-mediated
      signaling. Antioxid. Redox Signal. 00, 000-000.

PMID- 29635932
TI  - 2017 Diabetic Foot Conference Abstracts.

PMID- 29635931
TI  - Health Sensors, Smart Home Devices, and the Internet of Medical Things: An
      Opportunity for Dramatic Improvement in Care for the Lower Extremity
      Complications of Diabetes.
AB  - OBJECTIVE: The prevalent and long-neglected diabetic foot ulcer (DFU) and its
      related complications rank among the most debilitating and costly sequelae of
      diabetes. With the rise of the Internet of medical things (IoMT), along with
      smart devices, the med-tech industry is on the cusp of a home-care revolution,
      which could also create opportunity for developing effective solutions with
      significant potential to reduce DFU-associated costs and saving limbs. This
      article discusses potential applications of IoMT to the DFU patient population
      and beyond. METHODS: To better understand potential opportunities and challenges
      associated with implementing IoMT for management of DFU, the authors reviewed
      recent relevant literatures and included their own expert opinions from a
      multidisciplinary point of view including podiatry, engineering, and data
      security. RESULTS: The IoMT has opened digital transformation of home-based
      diabetic foot care, as it enables promoting patient engagement, personalized care
      and smart management of chronic and noncommunicable diseases through individual
      data-driven treatment regimens, telecommunication, data mining, and comprehensive
      feedback tailored to individual requirements. In particular, with recent advances
      in voice-activated commands technology and its integration as a part of IoMT, new
      opportunities have emerged to improve the patient's central role and
      responsibility in enabling an optimized health care ecosystem. CONCLUSIONS: The
      IoMT has opened new opportunities in health care from remote monitoring to smart
      sensors and medical device integration. While it is at its early stage of
      development, ultimately we envisage a connected home that, using voice-controlled
      technology and Bluetooth-radio-connected add-ons, may augment much of what home
      health does today.

PMID- 29635933
TI  - Multiple domains of social support are associated with diabetes self-management
      among Veterans.
AB  - Objectives To examine, among Veterans, relationships of general social support
      and diabetes-specific social support for physical activity and healthy eating
      with diabetes self-management behaviors. Methods Patients from VA Puget Sound,
      Seattle completed a cross-sectional survey in 2012-2013 ( N = 717). We measured
      (a) general social support and (b) diabetes-specific social support for healthy
      eating and physical activity with domains reflecting support person
      participation, encouragement, and sharing ideas. Among 189 self-reporting
      diabetes patients, we fit linear and modified Poisson regression models
      estimating associations of social support with diabetes self-management
      behaviors: adherence to general and diabetes-specific diets and blood glucose
      monitoring (days/week); physical activity (< vs. >=150 min/week); and smoking
      status (smoker/non-smoker). Results General social support was not associated
      with diabetes self-management. For diabetes-specific social support, higher
      healthy eating support scores across all domains were associated with better
      adherence to general and diabetes-specific diets. Higher physical activity
      support scores were positively associated with >=150 min/week of physical
      activity only for the participation domain. Discussion Diabetes-specific social
      support was a stronger and more consistent correlate of improved self-management
      than general social support, particularly for lifestyle behaviors. Incorporating
      family/friends into Veterans' diabetes self-management routines may lead to
      better self-management and improvements in disease control and outcomes.

PMID- 29635934
TI  - Levetiracetam Use in Peritoneal Dialysis.

PMID- 29635935
TI  - Factors associated to chronic migraine with medication overuse: A cross-sectional
      study.
AB  - BACKGROUND AND AIM: Factors implicated in the evolution of episodic migraine into
      chronic migraine are largely elusive. Medication overuse is considered to be one
      of the main determinants, but other possible clinical and psychological factors
      can play a role. The aim of this study is to identify factors that are associated
      with chronic migraine with medication overuse. METHOD: We enrolled consecutive
      migraine patients, subdividing them in two groups: Subjects with a long history
      of episodic migraine and subjects with chronic migraine and medication overuse.
      We then compared their clinical and psychological variables in a cross-sectional
      study. RESULTS: Three hundred and eighteen patients were enrolled, of which 156
      were episodic migraine and 162 were chronic migraine and medication overuse
      patients. The mean age was 42.1 +/- 10.3, 80.8% were female. The duration of
      migraine was 24.6 years in episodic migraine and 24.0 years in chronic migraine
      and medication overuse ( p = 0.57). After the multivariate analysis, the factors
      associated to chronic migraine and medication overuse were: Marital status
      (married vs. unmarried, OR 3.65, 95% CI 1.63-8.19, p = 0.002;
      separated/divorced/widowed vs. unmarried, OR 4.19, 95% CI 1.13-15.47, p = 0.031),
      physical activity (OR 0.42, 95% CI 0.19-0.91, p = 0.029), age at onset of
      migraine (OR 0.94, 95% CI 0.89-0.98, p = 0.016), use of at least one migraine
      preventive medication (OR 2.36, 95% CI 1.18-4.71, p = 0.014), history of
      depression (OR 2.91, 95% CI 1.25-6.73, p = 0.012), insomnia associated with the
      use of hypnotics (OR 5.59, 95% CI 1.65-18.93, p = 0.006), traumatic head injuries
      (OR 3.54, 95% CI 1.57-7.99, p = 0.002), snoring (OR 2.24, 95% CI 1.05-4.79, p =
      0.036), previous and/or actual use of combined oral contraceptives (OR 3.38, 95%
      CI 1.10-10.3, p = 0.031) and higher scores in the Childhood Trauma questionnaire
      (OR 1.48, 95% CI 1.09-2.02, p = 0.012). CONCLUSION: We considered several aspects
      that may be involved in the development of chronic migraine and medication
      overuse. A multivariate analysis identified 10 factors belonging to five
      different areas, to suggest that chronic migraine and medication overuse onset is
      likely influenced by a complex mixture of factors. This information is useful
      when planning strategies to prevent and manage chronic migraine and medication
      overuse.

PMID- 29635936
TI  - Chronorisk in cluster headache: A tool for individualised therapy?
AB  - BACKGROUND: The mechanisms behind the severe pain of cluster headache remain
      enigmatic. A distinguishing feature of the attacks is the striking rhythms with
      which they occur. We investigated whether statistical modelling can be used to
      describe 24-hour attack distributions and identify differences between subgroups.
      METHODS: Common hours of attacks for 351 cluster headache patients were
      collected. Probability distributions of attacks throughout the day (chronorisk)
      was calculated. These 24-hour distributions were analysed with a multimodal
      Gaussian fit identifying periods of elevated attack risk and a spectral analysis
      identifying oscillations in risk. RESULTS: The Gaussian model fit for the
      chronorisk distribution for all patients reporting diurnal rhythmicity (n = 286)
      had a goodness of fit R2 value of 0.97 and identified three times of increased
      risk peaking at 21:41, 02:02 and 06:23 hours. In subgroups, three to five modes
      of increased risk were found and goodness of fit values ranged from 0.85-0.99.
      Spectral analysis revealed multiple distinct oscillation frequencies in
      chronorisk in subgroups including a dominant circadian oscillation in episodic
      patients and an ultradian in chronic. CONCLUSIONS: Chronorisk in cluster headache
      can be characterised as a sum of individual, timed events of increased risk, each
      having a Gaussian distribution. In episodic cluster headache, attacks follow a
      circadian rhythmicity whereas, in the chronic variant, ultradian oscillations are
      dominant reflecting a loss of association with sleep and perhaps explaining
      observed differences in the effects of specific treatments. The results
      demonstrate the ability to accurately model chronobiological patterns in a
      primary headache.

PMID- 29635937
TI  - A pilot investigation of a mobile phone application and progressive reminder
      system to improve adherence to daily prevention treatment in adolescents and
      young adults with migraine.
AB  - BACKGROUND: Effective management of migraine requires adherence to treatment
      recommendations; however, adolescents with migraine take their daily medications
      only 75% of the time. Low-cost adherence-focused interventions using technology
      may improve adherence, but have not been investigated. METHODS: Thirty-five
      adolescents and young adults (13-21 years) with migraine participated in an AB
      design pilot study to assess the use of a mobile phone adherence-promotion
      application ("app") and progressive reminder system. Adherence was calculated
      using electronic monitoring during the baseline period and medication adherence
      intervention. RESULTS: Relative to baseline, adherence significantly improved
      during the first month of the intervention. Specifically, improvements existed
      for older participants with lower baseline adherence. Self-reported app-based
      adherence rates were significantly lower than electronically monitored adherence
      rates. Participants rated the intervention as acceptable and easy to use.
      CONCLUSIONS: "Apps" have the potential to improve medication adherence and are a
      promising intervention for adolescents and young adults with low adherence.
      Involving parents in the intervention is also helpful. Providers should assess
      barriers to adherence and use of technology-based interventions, encourage
      parents to incorporate behavioral incentives, and provide referrals for more
      intensive interventions to improve long-term outcomes. Further, tracking
      adherence in an app may result in an underestimation of adherence. Future full
      scale studies should be conducted to examine adherence promotion app
      interventions.

PMID- 29635938
TI  - Presence of vestibular symptoms and related disability in migraine with and
      without aura and chronic migraine.
AB  - Objective To assess the presence and handicap due to vestibular symptoms in three
      subgroups of patients with migraine and controls. Methods Women between 18-55
      years old were diagnosed by headache specialists and stratified as migraine with
      aura (n = 60), migraine without aura (n = 60), chronic migraine (n = 60) and
      controls (n = 60). Information regarding demographics, headache and vestibular
      symptoms were collected in this cross-sectional study. The self-perceived
      handicap related to vestibular symptoms was assessed through the Dizziness
      Handicap Inventory questionnaire. Results A total of 85% of women with migraine
      with aura and chronic migraine had vestibular symptoms contrasted to 70% of the
      migraine without aura group ( p < 0.05), and 12% of the control group reported
      symptoms ( p < 0.0001). Patients with migraine exhibited greater Dizziness
      Handicap Inventory scores than controls ( p < 0.001); and migraine with aura and
      chronic migraine groups reached greater scores than migraine without aura ( p <
      0.01). Presence of migraine is associated with a greater risk of vestibular
      symptoms (migraine without aura: 5.20, migraine with aura: 6.60, chronic
      migraine:6.20, p < 0.0003) and with a greater risk of moderate-to-severe handicap
      (migraine without aura: 20.0, migraine with aura: 40.0, chronic migraine: 40.0, p
      < 0.0003). The presence of aura and greater migraine frequency adds to the risk
      of any handicap (migraine with aura: 1.9, chronic migraine: 1.7, p < 0.04) and to
      the risk of moderate-to-severe handicap (migraine with aura: 2.0, chronic
      migraine: 2.0, p < 0.0003). Migraine aura, intensity and frequency predict 36% of
      the dizziness handicap. Conclusion The prevalence of vestibular symptoms is
      increased in migraine during and between headache attacks, particularly in
      migraine with aura and chronic migraine along with an increased handicap due to
      those symptoms. Vestibular symptoms among subgroups of migraine should be
      considered when evaluating the functional impact of migraine.

PMID- 29635939
TI  - Concept mapping to improve team work, team learning and care of the person with
      dementia and behavioural and psychological symptoms.
AB  - The incidence of behavioural and psychological symptoms of dementia in
      residential aged care facilities is high. Effective team work and knowledgeable
      staff are cited as important facilitators of appropriate care responses to
      clients with these symptoms, but to achieve this within a resource-poor workplace
      can be challenging. In the study reported in this paper, concept mapping was
      trialled to enhance multifocal person-centred assessment and care planning as
      well as team learning. The outcomes of team concept mapping were evaluated using
      a quasi-experimental design with pre- and post-testing in 11 selected Australian
      residential aged care facilities , including two control residential aged care
      facilities , over a nine-month period. It was demonstrated that use of concept
      mapping improved team function, measured as effectiveness of care planning, as
      well as enhancing learning, with increased knowledge of dementia care even
      amongst staff who were not directly involved with the process. It is suggested
      that these results may be generalizable to other countries and care settings.

PMID- 29635940
TI  - Primer in Genetics and Genomics Series: Final Remarks.

PMID- 29635941
TI  - The prevalence and predictors of elevated C-reactive protein after a coronary
      heart disease event.
AB  - Objective An interleukin-beta antagonist reduces the risk of subsequent
      cardiovascular events in coronary patients with high-sensitivity C-reactive
      protein (hs-CRP) >=2 mg/L. It remains to be defined how large the coronary
      population at inflammatory risk is, and what the predictors of elevated risk are.
      Methods A cross-sectional study investigated the proportion of patients with
      elevated hs-CRP (i.e. >=2 mg/L) and the respective demographic and clinical
      predictors in 971 patients without concomitant inflammatory diseases who had been
      hospitalized with myocardial infarction (80%) and/or a revascularization
      procedure. Data were collected from hospital records, a self-report questionnaire
      and a clinical examination with blood samples. Results After 2-36 month follow
      up, 39% ( n = 378) had hs-CRP >= 2 mg/L, among whom 64% ( n = 243) had low
      density lipoprotein cholesterol (LDL-C) >=1.8 mmol/L and 47% ( n = 176) used a
      low-intensity statin regime. Only 24% had both LDL and hs-CRP at target range,
      27% had elevation of both, whereas 12% had hs-CRP >= 2 mg/L and LDL-C < 1.8
      mmol/L. Somatic comorbidity (odds ratio (OR) 1.3/1.0 point on the Charlson
      score), >=1 previous coronary event (OR 2.4), smoking (OR 2.2), higher body mass
      index (OR 1.2/1.0 kg/m2), high LDL-C (OR 1.4/1.0 mmol/L) and higher anxiety
      scores (OR 1.1/1.0 point increase on the Hospital Anxiety and Depression Scale
      Anxiety subscale score) were significantly associated with hs-CRP >=2 mg/L in
      adjusted analyses. Conclusions Elevated hs-CRP was frequently observed after a
      coronary event and associated with unfavourable LDL-C and unhealthy lifestyles
      and psychosocial distress. Intensified statin therapy and strategies to target
      these modifiable factors are the encouraged first steps to reduce inflammation
      and improve LDL-C in these patients.

PMID- 29635942
TI  - Erratum.
AB  - The affiliations of the authors were incorrectly published in this article. SAGE
      regrets this error. The correct affiliations are listed below.

PMID- 29635944
TI  - Erratum.

PMID- 29635945
TI  - LC-MS-based lipidomics to examine acute rat pulmonary responses after nano- and
      fine-sized ZnO particle inhalation exposure.
AB  - Zinc oxide (ZnO) nano- and fine-sized particles are associated with respiratory
      toxicity in humans, but the underlying molecular mechanisms remain unclear. Our
      previous nuclear magnetic resonance-based metabolomic study demonstrated that
      changes in phosphorylcholine-containing lipids (PC-CLs) in the respiratory system
      were associated with ZnO particle-induced respiratory toxicity. However, the
      details of the lipid species associated with adverse effects and possible
      biomarker signatures have not been identified. Thus, a liquid chromatography-mass
      spectrometry (LC-MS)-based lipidomics platform was applied to examine the
      alterations of PC-CL species in the lungs of rats treated with a series of
      concentrations of nano-sized (35 nm) or fine-sized (250 nm) ZnO particles via
      inhalation. Principal component analysis (PCA), partial least squares
      discriminant analysis (PLS-DA), and the Mann-Whitney U (MWU) test with false
      discovery rate (FDR) control were conducted to explore the perturbed lipid
      species and to discriminate a potential pulmonary biomarker signature after ZnO
      particle exposure. The PCA and PLS-DA models revealed that the fine-sized ZnO
      particle-treated groups and the high-concentration nano-sized group were
      separated from the control groups as well as from the low and moderate nano-sized
      groups. The results from the MWU test further suggested that after FDR
      adjustment, numerous PC-CL species were altered in the high-concentration and
      moderate-concentration fine-sized groups. Furthermore, our results suggested that
      lipids involved in anti-oxidation, membrane conformation, and cellular signal
      transduction were altered in response to ZnO-induced oxidative stress and
      inflammation. One lipid, PC(18:0/18:1), exhibited good performance (AUC > 0.8) of
      discriminative ability in distinguishing ZnO particle exposure from the control.
      These findings not only provide a foundation for the exploration of possible ZnO
      particle-mediated mechanisms but also suggest a lipid biomarker for ZnO particle
      exposure.

PMID- 29635946
TI  - Neonatal acute kidney injury: recording rate, course, and outcome: one center
      experience.
AB  - BACKGROUND: Neonates, and particularly preterm newborns, are at increased risk
      for acute kidney injury (AKI) due to immature kidney function. While specific
      criteria have been defined for AKI in this particular population, this diagnosis
      is frequently overlooked, and consequently, is often not recorded in patients'
      medical files. AKI-associated short- and long-term morbidity and mortality
      underline the importance of this diagnosis Objective: To assess the recording
      rate of AKI in the neonatal intensive care unit (NICU), and to identify clinical
      features that may promote awareness to this condition. STUDY DESIGN: The database
      of one medical center was searched for serum creatinine values above 1 mg% among
      all the newborns (more than 48 hours old) who were hospitalized in the neonatal
      intensive care unit (NICU) during the years 2010-2015, and who underwent at least
      two blood tests during their hospitalization. The files of patients who met acute
      kidney injury (AKI) diagnostic criteria were searched for AKI diagnosis,
      maternal, fetal, and postnatal course and outcome. RESULTS: Of 59 newborns who
      met AKI criteria, 51 (86%) were preterm and 8 term newborns. The respective mean
      gestational weeks at birth were: 28 +/- 3 and 38.5 +/- 1, and mean birth weights:
      1002 +/- 57 and 3157 +/- 375 grams. Mortality rates were 14/51 (27%) versus 1/8
      (12.5%). Of the 44 survivors, AKI was recorded in the medical files of 9/37 (24%)
      preterm versus 5/7 (71%) term-newborns. AKI associated with twin pregnancy in
      preterm neonates: 22 (43%) versus 1 (12.5%) in term-newborn. Unexpected high
      frequencies of maternal obstetrical problems and cesarean section delivery: 62.5
      and 78%, respectively, along with persistently depressed 5-min Apgar 6.6 +/- 3.5
      were found in term newborns with AKI. Congenital anomalies of the urinary tract
      (CAKUT) were suspected prenatally on fetal ultrasound in 3 (6%) and 1 (12.5%) of
      the respective groups, a 10-fold higher rate than that observed in the general
      population. AKI recurred in 18 (35%) of the preterm and none of the term
      neonates. Mild AKI episodes (Stage 1-2) occurred in 30/37 (81%) by contrast to
      severe events (Stage 3) in 4/7 (57%) preterm and term survivors, respectively.
      Ventilation duration associated significantly with AKI recurrence, and sepsis
      with mortality: OR 1.25 (95%CI = 1.09-1.43) (p < .001) and OR = 4.65 (95%CI =
      1.26-17.2) (p = .014), respectively. CONCLUSIONS: We demonstrated underreporting
      of AKI, particularly among preterm newborns, a population at high risk of
      developing recurrent episodes. Our data suggest different clinical profiles of
      AKI among preterm and term neonates: with later onset, milder but recurrent
      episodes in the former. Increased alertness for AKI diagnosis is needed for
      neonates with prolonged respiratory support, treated with diuretics and after
      sepsis. Newborns suspected of CAKUT (Congenital Anomalies of Kidneys and Urinary
      Tract) as per fetal ultrasound might need closer observation for AKI occurrence.

PMID- 29635947
TI  - An update on the clinical pharmacokinetics of fexofenadine enantiomers.
AB  - INTRODUCTION: Fexofenadine is administered as a racemic mixture of (R)- and (S)
      enantiomers. The plasma concentrations of (R)-fexofenadine in humans are about
      1.5-fold higher than those of the (S)-enantiomer. Such differences in the
      pharmacokinetics between fexofenadine enantiomers are likely to be dependent on
      stereoselectivity for affinity to drug-transporters. Areas covered: This review
      focuses on elucidation of differences in clinical pharmacokinetics between
      fexofenadine enantiomers. Expert opinion: Differences in pharmacokinetics between
      fexofenadine enantiomers were caused by organic anion transporting polypeptide
      (OATP) 2B1, with a minor contribution from P-glycoprotein (P-gp). In vitro
      studies using OATP2B1 cRNA showed that (R)-fexofenadine uptake into oocytes is
      greater than (S)-enantiomer uptake. P-gp inducers, carbamazepine, and inhibitors
      such as itraconazole and verapamil show greater effects on the pharmacokinetics
      of (S)-fexofenadine. Apple juice and grape fruit juice, OATP2B1 inhibitors,
      significantly decrease the exposure of both fexofenadine enantiomers,
      particularly the (S)-enantiomer, but do not change the t1/2. Rifampicin
      significantly increases plasma concentrations of both enantiomers through
      inhibition of OATP1B3, whereas enantioselectivity of fexofenadine uptake by
      OATP1B3-expressing cells has not been observed. Combinations of multiple
      transporters such as OATP2B1 and P-gp facilitate enantioselective disposition of
      fexofenadine. Drug-transporters appear to be capable of chiral discrimination for
      transport of drugs with an asymmetric center.

PMID- 29635948
TI  - Prenatal diagnosis of Wolf-Hirschhorn syndrome at the first trimester using
      chromosomal microarray analysis.

PMID- 29635949
TI  - Multigroup Propensity Score Approach to Evaluating an Effectiveness Trial of the
      New Beginnings Program.
AB  - We used a multigroup propensity score approach to evaluate a randomized
      effectiveness trial of the New Beginnings Program (NBP), an intervention
      targeting divorced or separated families. Two features of effectiveness trials,
      high nonattendance rates and inclusion of an active control, make program effects
      harder to detect. To estimate program effects based on actual intervention
      participation, we created a synthetic inactive control comprised of nonattenders
      and assessed the impact of attending the NBP or active control relative to no
      intervention (inactive control). We estimated propensity scores using generalized
      boosted models and applied inverse probability of treatment weighting for the
      comparisons. Relative to the inactive control, NBP strengthened parenting quality
      as well as reduced child exposure to interparental conflict, parent psychological
      distress, and child internalizing problems. Some effects were moderated by parent
      gender, parent ethnicity, or child age. On the other hand, the effects of active
      versus inactive control were minimal for parenting and in the unexpected
      direction for child internalizing problems. Findings from the propensity score
      approach complement and enhance the interpretation of findings from the intention
      to-treat approach.

PMID- 29635950
TI  - What Is Lean Management in Health Care? Development of an Operational Definition
      for a Cochrane Systematic Review.
AB  - Industrial improvement approaches such as Lean management are increasingly being
      adopted in health care. Synthesis is necessary to ensure these approaches are
      evidence based and requires operationalization of concepts to ensure all relevant
      studies are included. This article outlines the process utilized to develop an
      operational definition of Lean in health care. The literature search, screening,
      data extraction, and data synthesis processes followed the recommendations
      outlined by the Cochrane Collaboration. Development of the operational definition
      utilized the methods prescribed by Kinsman et al. and Wieland et al. This
      involved extracting characteristics of Lean, synthesizing similar components to
      establish an operational definition, applying this definition, and updating the
      definition to address shortcomings. We identified two defining characteristics of
      Lean health-care management: (1) Lean philosophy, consisting of Lean principles
      and continuous improvement, and (2) Lean activities, which include Lean
      assessment activities and Lean improvement activities. The resulting operational
      definition requires that an organization or subunit of an organization had
      integrated Lean philosophy into the organization's mandate, guidelines, or
      policies and utilized at least one Lean assessment activity or Lean improvement
      activity. This operational definition of Lean management in health care will act
      as an objective screening criterion for our systematic review. To our knowledge,
      this is the first evidence-based operational definition of Lean management in
      health care.

PMID- 29635951
TI  - The role of prophylactic internal iliac artery ligation in abnormally invasive
      placenta undergoing caesarean hysterectomy: a randomized control trial.
AB  - OBJECTIVE: To identify the role of bilateral internal iliac artery (IIA) ligation
      on reducing blood loss in abnormally invasive placenta (AIP) undergoing caesarean
      hysterectomy. METHODS: In this parallel-randomized control trial, 57 pregnant
      females with ultrasound features suggestive of AIP were enrolled. They were
      randomized into two groups; IIA group (n = 29 cases) performed bilateral IIA
      ligation followed by caesarean hysterectomies, while Control group (n = 28 cases)
      underwent caesarean hysterectomy only. The main outcome was the difference in the
      estimated intraoperative blood loss between the two groups. RESULTS: There was no
      significant difference between the two groups regarding the intraoperative
      estimated blood loss (1632 +/- 804 versus 1698 +/- 1251, p value .83). The
      operative procedure duration (minutes) (223 +/- 66 versus 171 +/- 41.4, p value
      .001) varied significantly between the two groups. CONCLUSIONS: Bilateral
      internal iliac artery ligation, in cases of AIP undergoing caesarean
      hysterectomy, is not recommended for routine practice to minimize blood loss
      intraoperatively.

PMID- 29635953
TI  - Noninvasive, continuous, real-time glucose measurements compared to reference
      laboratory venous plasma glucose values.
AB  - PURPOSE: Current modalities for glucose monitoring are invasive and inconvenient.
      The search for a noninvasive technique is still ongoing, without a clinically
      viable product. The aim of our study was to evaluate the safety and accuracy of a
      novel non-invasive continuous glucometer - the WizmiTM device. METHODS:
      Prospective, observational, controlled clinical trial. We included healthy
      pregnant women designated to undergo a 3-hour oral glucose tolerance test. Each
      participant underwent synchronous and simultaneous glucose measurement by venous
      sampling of plasma glucose and non-invasive glucose by Wizmi device. Primary
      outcome was the accuracy of the Wizmi device as assessed by comparing between
      paired measurements, i.e. non-invasive glucose measurements by Wizmi versus
      standard plasma glucose levels, which were taken at the exact same time. RESULTS:
      Thirty-two women underwent oral glucose tolerance test (OGTT), contributing 224
      paired glucose measurements. Of the 224 paired measurements, all were within the
      clinically appropriate zones of the Clarke error grid analysis zones -208 (93%)
      in Zone A and 16 (7%) in zone B. Mean absolute relative difference of the Wizmi
      non-invasive glucose versus plasma glucose laboratory reference was 7.23% or 9.66
      mg/dl. Overall, for all 224 paired measurements, across all Wizmi glucose ranges,
      the agreement was 86.6, 92.0, 97.8 and 99.5% for deviations within +/-15, 20, 30,
      40% (if glucose >80 mg/dl) or mg/dl (if glucose <=80 mg/dl). CONCLUSIONS: Wizmi
      device is novel non-invasive continuous glucose monitor, safe to use, with
      overall high accuracy compared to a gold standard reference of plasma glucose.

PMID- 29635952
TI  - Nuchal cord: impact of umbilical artery Doppler indices on intrapartum and
      neonatal outcomes: a prospective cohort study.
AB  - BACKGROUND/OBJECTIVE: The purpose of this study is to investigate the use of a
      more biologic parameter for evaluation of the effect of nuchal cord tightness;
      the study of blood flow in the umbilical arteries of nuchal cord using Doppler
      ultrasonography. METHODS: This prospective cohort study was conducted at Ain
      Shams University Maternity Hospital, Cairo, Egypt in the period between August
      2015 and August 2017. Hundred primigravidas were recruited with nuchal cord
      diagnosed by Doppler ultrasonography; whereas the rest of the study population
      was included in the "Control group". Doppler velocimetry study was then performed
      on a free-floating loop of the umbilical cord and Doppler indices were
      calculated. Both groups were followed up during labor: intrapartum events, mode
      of delivery, and neonatal outcome were recorded. RESULTS: Intrapartum fetal heart
      rate abnormalities were significantly more common in the nuchal cord group
      compared to the control group. The overall cardiotocography category was
      significantly more commonly reflecting abnormal fetal heart rate patterns in the
      nuchal cord group compared to the control group with 46.74% of the nuchal group
      patients falling within the "suspicious - pathological - need urgent
      intervention" categories. Intervention rate was significantly higher in the
      nuchal cord group than the control group (33.69 versus 21.84%). Moreover,
      incidence of intrapartum fetal heart rate abnormalities and intervention rate
      were significantly higher in the nuchal cord with abnormal Doppler subgroup
      compared to both nuchal cord with normal Doppler subgroup and the control group;
      with a calculated number needed to harm of 2.11. CONCLUSIONS: In view of these
      results, it might be concluded that umbilical cord tightness affecting fetal
      hemodynamics (expressed by changes in umbilical artery Doppler) might be a
      determinate factor affecting the intrapartum course.

PMID- 29635954
TI  - Pelvic floor muscle function and EMG in nulliparous women of different ages: a
      cross-sectional study.
AB  - BACKGROUND: Although aging is considered a risk factor for pelvic floor muscle
      dysfunction (PFMD), the effect of aging on the function of the pelvic floor
      muscles (PFM) remains unclear. OBJECTIVE: To compare PFM function and activity in
      nulliparous women in different age groups. METHODS: This was a cross-sectional
      study in which 70 women with ages between 18 and 69 years were divided into five
      age groups for evaluation. Initially, medical histories were taken, and then the
      PFM function was assessed using digital palpation (Modified Oxford Scale),
      manometry and surface electromyography (sEMG). The Kruskal-Wallis test was
      applied to check the differences between the groups. The Spearman correlation
      coefficient was used to verify the correlations between age and PFM function,
      manometry values and sEMG. A significance level of 5% was adopted. RESULTS: No
      significant differences were observed between the different age groups in PFM
      digital palpation, manometry values and sEMG. There was a low negative
      correlation between age root mean square and peak of sEMG signals. CONCLUSION:
      This study found no difference in PFM function and activity between nulliparous
      women in the five different age groups. Future long-term large prospective
      studies are required to confirm these findings.

PMID- 29635956
TI  - Osteoarthritis progression of the shoulder: A long-term follow-up after mini-open
      rotator cuff repair.
AB  - OBJECTIVE: This study aimed to investigate whether (1) the primary repair of
      rotator cuff tears can prevent the progression of osteoarthritis (OA) and (2) the
      quality of postoperative cuff integrity affects the incidence of osteoarthritic
      changes. METHODS: A total of 86 patients treated with mini-open repair for
      rotator cuff tears over a minimum of 10 years of follow-up (mean +/- standard
      deviation 11.1 +/- 1.0 years) were retrospectively analyzed. Preoperative and
      postoperative radiographs of the affected and unaffected sides were compared, and
      the degree of OA was evaluated using the Samilson and Prieto classification.
      Magnetic resonance imaging was used to evaluate cuff integrity, classify patients
      into good and poor cuff integrity groups, and compare the degree of OA between
      the two groups. RESULTS: OA deteriorated either significantly or to a similar
      degree on both sides postoperatively. However, OA progressed in significantly
      more cases on the affected side. A comparison between the aforementioned cuff
      integrity groups showed that the postoperative OA of the poor cuff integrity
      group was significantly worse than that of the good cuff integrity group on the
      affected side. CONCLUSION: Our study showed that even if rotator cuff tears are
      repaired, the progression of osteoarthritic changes cannot be halted. The
      progression of OA was affected by cuff integrity. Rotator cuff dysfunction due to
      poor cuff integrity was a risk factor for shoulder arthritis.

PMID- 29635957
TI  - Analysis of glenohumeral morphological factors for anterior shoulder instability
      and rotator cuff tear by magnetic resonance imaging.
AB  - OBJECTIVE: The aim of this study was to investigate whether there are
      glenohumeral morphological differences between normal population, glenohumeral
      instability, and rotator cuff pathology. METHOD: In this study, shoulder magnetic
      resonance (MR) images of 150 patients were evaluated. Patients included in the
      study were studied in three groups of 50 individuals: patients with anterior
      shoulder instability in group 1, patients with rotator cuff tear in group 2, and
      control subjects without shoulder pathology in group 3. RESULTS: There were
      statistically significant differences between groups in evaluations for glenoid
      version, glenoid coronal height, glenoid coronal diameter, humeral axial and
      coronal diameters, and coracohumeral interval distances. Significant differences
      were observed between groups 2 and 3 in glenoid axial diameter, glenoid coronal
      height, glenoid depth, humeral coronal diameter, and coracohumeral distances.
      CONCLUSION: The results obtained in this study suggest that glenoid version,
      glenoid coronal height and diameter, humeral diameter, and coracohumeral interval
      parameters in glenohumeral morphology-related parameters in patients with
      anterior instability are different from those of normal population and patients
      with rotator cuff pathology. In cases where there is a clinically difficult
      diagnosis, these radiological measurements will be helpful to clinicians in
      diagnosis and treatment planning, especially in cases of treatment-resistant
      cases.

PMID- 29635958
TI  - Hydrogen peroxide promotes the activation of preeclampsia peripheral T cells.
AB  - Preeclampsia (PE) is a pregnancy disorder with a high mortality rate. Patients
      with PE exhibit systemic high oxidative stress status and inflammatory immune
      activation. This study aims to define the role of H2O2 in the activation of
      neutrophils and T lymphocytes in PE patients. CD3+/HLA-DR+ cells in blood from PE
      patients are remarkably increased compared with those of normal non-pregnancies
      or normal pregnancies, while the percentage of CD3+/CD62L+ cells is significantly
      reduced in PE patients compared to normal pregnancies. Furthermore, CD62L levels
      in granulocytes of periphery blood of PE patients are significantly higher than
      non-pregnancies, but significantly lower than normal pregnancies. To characterize
      the effects of intracellular reactive oxygen species (ROS) on T lymphocyte
      activation in PE patients, PBMCs from normal pregnancies were challenged with
      H2O2, and intracellular ROS levels in neutrophil granulocytes, as well as T cell
      surface marker levels, have been determined. We confirm that H2O2 exposure
      increases intracellular ROS levels in neutrophil granulocytes, and increases the
      proportion of CD3+/HLA-DR+ cells, but does not alter the percentage of
      CD3+/CD62L+ cells in PBMCs. Our study has confirmed dysregulated CD3+/HLA-DR+ and
      CD3+/CD62L+ T lymphocytes in PE patient peripheral blood, and the dysregulative
      effects of H2O2 on T lymphocyte activation, suggesting a novel mechanism of
      immune activation in PE.

PMID- 29635959
TI  - Exploring the diet and lifestyle changes contributing to weight gain among
      Australian West African women following migration: A qualitative study.
AB  - AIMS AND OBJECTIVES: This paper reports on women's experiences of weight gain and
      obesity as they became acculturated to the Australian diet and lifestyle.
      BACKGROUND: Migrants from sub-Saharan Africa have a much higher risk of obesity
      than the native population when settling in industrialised countries. METHOD:
      Qualitative. RESULTS: Women in this study reported weight gain post-migration.
      This was attributed to increased access to a wide variety of food including
      takeaway food and more sedentary lifestyles. CONCLUSIONS: Obesity has long-term
      consequences for health and well-being. Further research is needed to support a
      healthy transition to life in Australia. RELEVANCE TO CLINICAL PRACTICE: Gaining
      insight into the underlying reasons that West African immigrants to Australia
      become obese could contribute to assisting health professionals design culturally
      appropriate interventions and health education programmes to support new
      arrivals.

PMID- 29635960
TI  - Abdominal organ protection strategy for aortic arch aneurysm surgery.
AB  - INTRODUCTION: Body temperature maintained during open distal anastomosis in
      patients who undergo aortic surgery has been showing an upward trend; however, a
      higher temperature may increase visceral organ and spinal cord injury. Distal
      perfusion may reduce abdominal organ injury, especially acute kidney injury
      (AKI). METHODS: From 2009 to 2016, 56 patients who underwent ascending aortic
      and/or aortic arch surgery were enrolled. Open distal anastomosis was performed
      using one of three protection strategies: 1) systemic temperature of 25 degrees C
      followed by selective cerebral perfusion (SCP) with lower body circulatory arrest
      (Group CA25, n=27); 2) systemic temperature of 28 degrees C followed by SCP with
      lower body circulatory arrest (Group CA28, n=4); and 3) systemic temperature of
      28 degrees C followed by SCP with distal aortic perfusion (Group DP, n=25).
      RESULTS: During the postoperative course, levels of blood urea nitrogen,
      creatinine, liver enzymes, lactate dehydrogenase and lactate in Groups CA28 and
      CA25 were significantly higher than those in Group DP. AKI defined by the AKI
      Network occurred in 28 cases (50%) and 3 cases required permanent hemodialysis.
      AKI was significantly higher in Groups CA25 and CA28 than in Group DP (p=0.026).
      Mid-term follow-up showed that patients who developed postoperative AKI were more
      likely to suffer from cardiovascular events. CONCLUSIONS: Distal perfusion during
      open distal anastomosis reduced kidney and liver injury after thoracic aortic
      surgery despite an increased body temperature of up to 28 degrees C. This
      strategy may be useful to prevent AKI, liver dysfunction, the need for
      hemodialysis and multiple organ failure and could improve mid-term results.

PMID- 29635961
TI  - Extended negative binomial hurdle models.
AB  - Poisson models are widely used for statistical inference on count data. However,
      zero-inflation or zero-deflation with either overdispersion or underdispersion
      could occur. Currently, there is no available model for count data, that allows
      excessive occurrence of zeros along with underdispersion in non-zero counts, even
      though there have been reported necessity of such models. Furthermore, given an
      excessive zero rate, we need a model that allows a larger degree of
      overdispersion than existing models. In this paper, we use a random-effect model
      to produce a general statistical model for accommodating such phenomenon
      occurring in real data analyses.

PMID- 29635962
TI  - An omnibus test for the global null hypothesis.
AB  - Global hypothesis tests are a useful tool in the context of clinical trials,
      genetic studies, or meta-analyses, when researchers are not interested in testing
      individual hypotheses, but in testing whether none of the hypotheses is false.
      There are several possibilities how to test the global null hypothesis when the
      individual null hypotheses are independent. If it is assumed that many of the
      individual null hypotheses are false, combination tests have been recommended to
      maximize power. If, however, it is assumed that only one or a few null hypotheses
      are false, global tests based on individual test statistics are more powerful
      (e.g. Bonferroni or Simes test). However, usually there is no a priori knowledge
      on the number of false individual null hypotheses. We therefore propose an
      omnibus test based on cumulative sums of the transformed p-values. We show that
      this test yields an impressive overall performance. The proposed method is
      implemented in an R-package called omnibus.

PMID- 29635963
TI  - Tau-independent Phase Analysis: A Novel Method for Accurately Determining Phase
      Shifts.
AB  - Estimations of period and phase are essential in circadian biology. While many
      techniques exist for estimating period, comparatively few methods are available
      for estimating phase. Current approaches to analyzing phase often vary between
      studies and are sensitive to coincident changes in period and the stage of the
      circadian cycle at which the stimulus occurs. Here we propose a new technique,
      tau-independent phase analysis (TIPA), for quantifying phase shifts in multiple
      types of circadian time-course data. Through comprehensive simulations, we show
      that TIPA is both more accurate and more precise than the standard actogram
      approach. TIPA is computationally simple and therefore will enable accurate and
      reproducible quantification of phase shifts across multiple subfields of
      chronobiology.

PMID- 29635964
TI  - Validation of the Reading the Mind in the Eyes Test in a healthy Spanish sample
      and women with anorexia nervosa.
AB  - INTRODUCTION: The aim of this study was to build a Spanish version of the Reading
      the Mind in the Eyes Test (RMET) including limited time of response and an
      integrated glossary, and to test its validity. METHODS: A total of 433 university
      students (121 men and 350 women) and 38 anorexic women completed the RMET and
      other related measures of empathy and alexithymia. The results of the Parallel
      Analysis suggested a unidimensional structure for 19 items, which was verified
      through a Confirmatory Factor Analysis. RESULTS: Similarly to other research,
      this factor had a low reliability (alpha = .56, rho = .59); however, regarding
      validity, the total score of the instrument showed positive correlations with
      empathy and negatives with alexithymia. Furthermore, healthy females were
      superior to males in RMET, and to anorexic women; but no significant differences
      appeared between healthy men and the anorexic group. CONCLUSION: This study
      confirms the validity of the test and permits a relatively short and inexpensive
      means of administration in large samples of adults. Besides, it suggests the
      necessity of assessing and treating the theory of mind in anorexic women.

PMID- 29635965
TI  - Diagnosis and endovascular treatment of iliac venous compression syndrome.
AB  - Objectives To report *The first two authors contributed equally to this work. our
      clinical experience on diagnostic criteria and endovascular management in
      patients with iliac venous compression syndrome. Method Between July 2013 and May
      2015, 85 consecutive patients with suspected iliac venous compression syndrome
      were evaluated by transfemoral venography and intravascular ultrasonography.
      Venographic evidence of iliac venous occlusion, stenosis, or pelvic collateral
      vessels, and the degree of stenosis as examined with intravascular
      ultrasonography were recorded. The endovascular procedure, complications,
      clinical outcome, and the Venous Clinical Severity Score were evaluated before
      and after the intervention. Results Of the 85 limbs, 66 cases of iliac venous
      compression syndrome were confirmed and 19 cases were excluded. In all of the 66
      patients, we successfully performed endovascular intervention (22 balloon
      dilations, 44 balloon dilations + stenting). Two patients with stent implantation
      developed acute lower extremity deep vein thrombosis, resulted in successful
      lysis of the thrombus with catheter-directed thrombolysis. Conclusions The
      presence of intraluminal spurs and pelvic collateral vessels represents not only
      pathological and anatomical changes by long-term mechanical compression, but also
      indicators of the severity of iliac venous compression syndrome. The degree of
      stenosis cannot accurately represent the severity and treatment of iliac venous
      compression syndrome, especially in the right iliac vein. Endovascular
      intervention is a safe and effective treatment that reduces lower extremity
      symptoms. Full and intentional dilation of the intraluminal spurs is an important
      technical aspect, which is often ignored.

PMID- 29635966
TI  - A survey of mobile phone use in the provision of palliative care services in the
      African region and priorities for future development.
AB  - Introduction Palliative care (PC) services in the African region need to adapt to
      manage rising numbers of patients with cancer or other life-limiting conditions.
      Mobile phone use in healthcare delivery (mHealth) is at an early stage of
      development for PC, but may provide new approaches to supporting patients
      regionally, particularly those with non-communicable diseases. Methods We
      conducted an online survey of 51 PC providers across 21 countries in the African
      region to identify: (i) current mHealth use in PC service delivery; (ii)
      potential barriers to mHealth use; and (iii) provider priorities for research
      development. Results mHealth approaches were reported across 71.4% of services in
      which respondents were based. Barriers to mHealth research include patients not
      having access to phones, mobile network access, and limited access to expertise
      and hardware required for mHealth. Research priorities were identified which
      included exploring ways of incorporating mHealth into patient care and ensuring
      access and relevance of mHealth for patients and health professionals. Discussion
      mHealth approaches are present across PC services in the African region, but so
      too are barriers to their use. Further work is required to explore how existing
      mHealth activities might be further developed and aligned with priority areas for
      PC development. Crucially, user engagement that seeks to understand the
      preferences and priorities of patients with PC needs, their caregivers, and those
      involved in the provision of PC should remain central to these efforts.

PMID- 29635967
TI  - Anabolic-androgenic steroid use and correlates in Norwegian adolescents.
AB  - This paper surveys the prevalence and correlates of anabolic androgenic steroids
      (AAS) use among Norwegian adolescents, and examines the degree to which sports
      participation is a mediating or moderating factor to well-known correlations
      between AAS use and problem behaviour. The data come from the "Ungdata" study, a
      cross-national youth survey system offered to all municipalities in Norway
      (response rate: 74%, N = 77,572). The study demonstrates a lifetime prevalence of
      AAS use of 1.27% and a higher prevalence among boys (1.81%) than girls (0.76%).
      The analyses show that AAS use is clearly related to problem behaviour such as
      violence and other substance use. When controlling for problem behaviour, there
      are no correlations between AAS use and exercising in a sports club or on one's
      own, whilst there is a weak positive correlation between AAS use and exercising
      in a gym or engaging in other forms of physical exercise such as dancing or
      martial arts. These patterns are more or less the same for boys and for girls. We
      conclude that adolescent AAS use is a low-prevalence phenomenon that primarily
      takes place in smaller subgroups of individuals who engage in other forms of
      problem behaviour as well.

PMID- 29635968
TI  - Kallikreins Stepwise Scoring Reveals Three Subtypes of Papillary Thyroid Cancer
      with Prognostic Implications.
AB  - BACKGROUND: Papillary thyroid cancer (PTC) is the most common type of thyroid
      cancer. Unlike most cancers, its incidence has dramatically increased in the last
      decades mainly due to increased diagnosis of indolent PTCs. Adequate risk
      stratification is crucial to avoid the over-treatment of low-risk patients, as
      well as the under-treatment of high-risk patients, but the currently available
      markers are still insufficient. Kallikreins (KLKs) are emergent biomarkers in
      cancer, but their involvement in PTC is unknown. METHODS: This study analyzed DNA
      methylation (HumanMethylation arrays) and gene expression (RNA-Seq) of KLKs, BRAF
      and RAS mutations, and clinical data from four published thyroid cancer data sets
      including normal and tumor tissues (n = 73, n = 475, n = 20, and n = 82) as
      discovery, training, and validation series. The C4.5 classification algorithm was
      used to generate a decision tree. Disease-free survival was estimated using
      Kaplan-Meier and Cox approaches. Specific analyses were performed using real-time
      polymerase chain reaction and immunohistochemistry. RESULTS: The entire KLK
      family was deregulated in PTC, displaying a specific epigenetic and
      transcriptional profile strongly associated with BRAFV600E or RAS mutations.
      Thus, a decision-tree algorithm was developed based on three KLKs with >80%
      sensitivity and >95% specificity, identifying BRAF- and RAS-mutated tumors.
      Notably, tumors lacking these mutations were classified as BRAF- or RAS-like.
      Most importantly, the KLK algorithm uncovered a novel PTC subtype showing
      favorable prognostic features. CONCLUSIONS: The KLK algorithm could lead to a new
      clinically applicable strategy with important implications for the risk
      stratification of PTC and the management of patients.

PMID- 29635969
TI  - Investigating the use of pre-training measures of autonomic regulation for
      assessing functional overreaching in endurance athletes.
AB  - The use of heart rate variability (HRV) to inform daily training prescription is
      becoming common in endurance sport. Few studies, however, have investigated the
      use of pre-training HRV to predict decreased performance or altered exercising
      autonomic response, typical of functional overreaching (FOR). Further, a new
      cardiac vagal tone (ProCVT) technology purports to eliminate some of the noise
      associated with daily HRV, and therefore may be better at predicting same-day
      performance. The purpose of this investigation was to examine if changes to
      resting HRV and ProCVT were associated with alterations in performance, maximal
      heart rate (HRmax), or heart rate recovery (HRrec) in FOR athletes. Twenty-eight
      recreational cyclists and triathletes were assigned to experimental/control
      conditions and underwent: 1 week of reduced training, 3 weeks of overload (OL) or
      regular training (CON), and 1 week of recovery. Testing occurred following the
      reduced training week (T1), post-3 weeks of training (T2), and following the
      recovery week (T3). Measures of resting HRV/ProCVT were collected each testing
      session, followed by maximal incremental exercise tests with HRrec taken 60 s
      post-exercise. Performance decreased from T1 to T2 in the OL group vs. CON (Delta
      9 +/- 12 vs. Delta9 +/- 11 W, P < .001), as did HRmax (Delta-8 +/- 4 vs. Delta-2
      +/- 4 bpm, P < .001). HRrec increased from T1 to T2 in the OL group vs. CON
      (Delta10 +/- 9 vs. Delta2 +/- 5 beats/min, P < .01). HRV and ProCVT did not
      change in either group. Same-day resting autonomic measures are insufficient in
      predicting alterations to performance or exercising HR measures following
      overload training.

PMID- 29635970
TI  - Bone mineral density changes in the graft after acetabular impaction bone
      grafting in primary and revision hip surgery.
AB  - Background and purpose - Impaction bone grafting (IBG) is an established method
      in hip revision surgery to reconstruct loss of bone stock. There is limited
      knowledge concerning the actual bone remodelling process within the allograft. We
      investigated with repeated bone mineral density (BMD) measurements the biological
      process of bone remodelling in the allograft in vivo. We hypothesized that an
      initial decrease in BMD would be followed by an increase towards baseline values.
      Patients and methods - Dual-energy X-ray absorptiometry (DXA) was used to measure
      BMD values in 3 regions of interest (ROI) in 20 patients (average age at surgery
      70 years, 11 males) after an acetabular reconstruction with IBG and a cemented
      cup. A postoperative DXA was used as baseline and DXA was repeated at 3 and 6
      months and at 1 and 2 years. The Oxford Hip Score (OHS), the 12-Item Short Form
      Health Survey (SF12), and a 0 to 100 mm visual analogue scale (VAS) for pain and
      satisfaction were obtained simultaneously. Results - The overall mean BMD in the
      IBG regions increased significantly by 9% (95% CI 2-15) at 2 years' follow-up. In
      the cranial ROI BMD increased 14% (CI 6-22), whereas the BMD in the medial and
      caudal ROI showed an increase of 10% (CI 1-18) and 4% (CI -6-16), respectively.
      The OHS, SF12-mental, and VAS for pain all improved statistically significantly 2
      years after surgery, with a mean VAS for satisfaction of 77 (CI 63-90) out of 100
      points. The SF12-physical showed non-significant improvement. Interpretation -
      The BMD in the allograft gradually increased after IBG for acetabular
      reconstruction arthroplasties, particularly in the cranial ROI. An initial
      decrease in the BMD was not encountered. These BMD changes, as proxy measurements
      for bone remodeling, may indicate progressive apposition of vital new host bone
      in the grafted area.

PMID- 29635971
TI  - Osteochondral lesions of the talus.
AB  - Background and purpose - The frequency of progression of osteoarthritis and
      persistence of symptoms in untreated osteochondral lesion of the talus (OCL) is
      not well known. We report the outcome of a nonoperative treatment for symptomatic
      OCL. Patients and methods - This study included 142 patients with OCLs from 2003
      to 2013. The patients did not undergo immobilization and had no restrictions of
      physical activities. The mean follow-up time was 6 (3-10) years. Initial MRI and
      CT confirmed OCL and showed lesion size, location, and stage of the lesion.
      Progression of osteoarthritis was evaluated by standing radiographs. In 83
      patients, CT was performed at the final follow-up for analyses of the lesion
      size. We surveyed patients for limitations of sports activity, and Visual
      Analogue Scales (VAS), AOFAS, and SF-36 were assessed. Results - No patients had
      progression of osteoarthritis. The lesion size as determined by CT did not change
      in 69/83 patients, decreased in 5, and increased in 9. The mean VAS score of the
      142 patients decreased from 3.8 to 0.9 (p < 0.001), the mean AOFAS ankle-hindfoot
      score increased from 86 to 93 (p < 0.001), and the mean SF-36 score increased
      from 52 to 72 (p < 0.001). Only 9 patients reported limitations of sports
      activity. The size and location of the lesion did not correlate with any of the
      outcome scores. Interpretation - Nonoperative treatment can be considered a good
      option for patients with OCL.

PMID- 29635972
TI  - Introduction to human factors and ergonomics.

PMID- 29635974
TI  - A Bayesian two-stage spatially dependent variable selection model for space-time
      health data.
AB  - In space-time epidemiological modeling, most studies have considered the overall
      variations in relative risk to better estimate the effects of risk factors on
      health outcomes. However, the associations between risk factors and health
      outcomes may vary across space and time. Especially, the temporal patterns of the
      covariate effects may depend on space. Thus, we propose a Bayesian two-stage
      spatially dependent variable selection approach for space-time health data to
      determine the spatially varying subsets of regression coefficients with common
      temporal dependence. The two-stage structure allows reduction of the spatial
      confounding bias in the estimates of the regression coefficients. A simulation
      study is conducted to examine the performance of the proposed two-stage model. We
      apply the proposed model to the number of inpatients with lung cancer in 159
      counties of Georgia, USA.

PMID- 29635975
TI  - Bootstrap-based testing approaches for the assessment of the diagnostic accuracy
      of biomarkers subject to a limit of detection.
AB  - Assessment of the diagnostic accuracy of biomarkers through receiver operating
      characteristic curve analysis frequently involves a limit of detection imposed by
      the laboratory analytical system precision. As a consequence, measurements below
      a certain level are undetectable and ignoring these is known to lead to
      negatively biased estimates of the area under the receiver operating
      characteristic curve. In this article, we introduce two receiver operating
      characteristic curve-based parametric approaches that tackle the issue of correct
      assessment of diagnostic markers in the presence of a limit of detection.
      Proposed approaches are simulation-based utilising bootstrap methodology. Non
      parametric alternatives that are naively used in the literature do not solve the
      inherent problem of limit of detection values which are treated as censored
      observations. However, the latter seems to perform adequately well in our
      simulation study. Nonparametric bootstrap was consistently used throughout, while
      other bootstrap alternatives performed similarly in our pilot simulation study.
      The simulation study involves the comparison of parametric and non-parametric
      options described here versus alternative strategies that are routinely used in
      the literature. We apply all methods to a study-setting resembling a chemical
      quasi-standard situation, where compound tumour biomarkers were searched within a
      multi-variable set of measurements to discriminate between two groups, namely
      colorectal cancer and controls. We focus in the assessment of glutamine and
      methionine.

PMID- 29635976
TI  - Disability and health outcomes - from a cohort of people on long-term anti
      retroviral therapy.
AB  - Human-immunodeficiency virus (HIV)/Acquired immunodeficiency Syndrome (AIDS)
      remains a major health problem in South Africa - even after two decades since the
      introduction of antiretroviral therapy (ART). Long-term survival with HIV is
      associated with new health-related issues and a risk of functional
      limitation/disability. The aim of this study was to assess functional limitation
      associated with HIV/AIDS among people living with HIV (PLHIV) in South Africa.
      This study is a cross-sectional survey using a cohort in an urban area in Gauteng
      province, South Africa. Data were collected using questionnaires through an
      interview process. The information collected included aspects such as
      demographics, livelihood, the state of mental and physical health, adherence and
      disability. A total of 1044 participants with an average age of 42 +/- 12 years
      were included in the study, with 51.9% of the participants reporting functional
      limitations (WHODAS >= 2). These were reported mainly in the domains of
      participation (40.2%) and mobility (38.7%). In addition, adherence to ART,
      symptoms of poor physical health and depression were strongly associated with
      their functional limitations/disability. HIV as a chronic disease is associated
      with functional limitations that are not adequately addressed and pose a risk of
      long-term disability and negative adherence outcomes. Therefore, wellness for
      PLHIV/AIDS needs to include interventions that can prevent and manage disability.

PMID- 29635977
TI  - The Sharing of Research Data in the Cell & Tissue Engineering Area: Is It a
      Common Practice?
AB  - The availability of research data sets is an important milestone because it can
      enhance the dynamics of research. This study aims to analyze the PubMed Central
      repository to determine the availability and type of raw data sets in Cell &
      Tissue Engineering journals indexed in Journal Citation Reports. The number and
      types of files were registered. The main finding of this study is that, beyond
      the mandatory deposit of data in specific repositories that some journals
      require, the exchange of data as supplementary material in the Cell & Tissue
      Engineering journals is not a common practice since researchers are still
      reticent to do so.

PMID- 29635978
TI  - Brn2 Alone Is Sufficient to Convert Astrocytes into Neural Progenitors and
      Neurons.
AB  - Generating neurons or neural progenitor cells (NPCs) from astrocytes is a
      potential strategy for neurological repair by reprogramming. Previous study has
      showed that Brn2, by cooperating with other factors, participates in neurogenesis
      and neuronal reprogramming. However, it is still unclear whether the Brn2 alone
      can convert astrocytes into neurons or NPCs. Here, we explored the effect of Brn2
      on reprogramming of astrocytes, and found that a single transcription factor Brn2
      can convert mouse astrocytes into functional neurons. Furthermore, the Brn2
      infected astrocytes can be induced into NPCs after changing culture condition. In
      addition, our study found that the reprogramming of astrocytes and the fate of
      transdifferentiated cells are closely associated with cell microenvironmental
      factors, such as the brain regions where the astrocytes come from, the
      proliferation ability of astrocytes, and culture condition of infected
      astrocytes. To sum up, for the first time, our results demonstrated that Brn2
      alone is sufficient to convert astrocytes into neural progenitors and neurons,
      and the conversion is associated with cell microenvironments. This new conversion
      method will be a potential therapeutic approach to restore the injured diseased
      brain in regenerative medicine.

PMID- 29635980
TI  - Professor Krystyna Kotelko and her contribution to the study of Proteus
      endotoxin.
AB  - Professor Krystyna Kotelko was working as a microbiologist at the University of
      Lodz (Poland). Her main object of study was the LPS (endotoxin) of opportunistic
      urinary pathogens from the genus Proteus. She demonstrated, for the first time,
      the presence of uronic acids and amino acids, as well as two heptoses (L- glycero
      D- manno-heptose and D- glycero-D- manno-heptose) and hexosamines in Proteus LPS,
      and developed a classification scheme of the Proteus LPS into chemotypes. Prof
      Kotelko also initiated studies on the chemical structure of Proteus O-specific
      polysaccharide and investigations on the serological specificity of this part of
      LPS, as well its core region. She also analysed the virulence factors of these
      bacteria, such as haemolysin and invasiveness.

PMID- 29635981
TI  - Plasma microRNA-21, microRNA-146a and IL-13 expression in asthmatic children.
AB  - Childhood asthma represents a worldwide problem, involving genetic, immune
      defense and environmental components. MicroRNAs (miRs) are non-coding, single
      stranded RNAs involved in immune regulation. The aim was to evaluate clinical
      potential of plasma miR-21 and miR-146a involved in T helper differentiation in
      childhood asthma and non-asthmatic controls. Group 1 consisted of 27 asthmatic
      children receiving inhaled corticosteroids (ICSs), which was compared to group 2
      with 21 healthy control children. All patients were assessed by pulmonary
      function tests. miR-21 and miR-146a expression levels were determined by real
      time quantitative PCR, and IL-13 was measured using ELISA. Group 1 showed
      significant up-regulation of plasma miR-21 and miR-146a levels with mean values
      42.6-fold and 4.7-fold higher than average expression, respectively, in group 2.
      miR-21 levels positively correlated with IL-13 levels and eosinophil percentage,
      while miR-146a only correlated to eosinophil percentage. There was a linear
      association between each of miR-21 and miR-146a expression and FEV1 (forced
      expiratory volume in the first second), miR-21 and miR-146a are up-regulated in
      asthmatic children. miR-21 served as a better asthma biomarker. Association
      between both markers and FEV1 points to their role in determining asthma outcome
      following ICS treatment. miR-21 and miR-146a play a role in eosinophilic
      endotypic classification of asthma.

PMID- 29635984
TI  - 'Marginal voices' - a quest to improve mental health diagnosis among the deaf
      community in the UK.

PMID- 29635986
TI  - Cultural postpartum practices of 'doing the month' in China.

PMID- 29635987
TI  - The power of the senses in public health.

PMID- 29635988
TI  - From high street to main street: revising and utilizing the Richter Scale for
      Health in an urban center in the US.

PMID- 29635989
TI  - Reducing tobacco smoke exposure for vulnerable groups: hospital settings and
      teachable moments.

PMID- 29635991
TI  - Medical students are well placed to promote health.

PMID- 29635992
TI  - Erratum.
AB  - Pasolini MP, Pagano TB, Costagliola A, et al. Inflammatory Myopathy in Horses
      With Chronic Piroplasmosis. Vet Path. 2017; 55(1):133-143. (Original DOI:
      10.1177/0300985817716262) In volume 55, issue 1, page 133, the tenth author
      Vincenzo Veneziano was incorrectly listed as Veneziano Veneziano. This has been
      corrected online.

PMID- 29635993
TI  - Promoting Global Health Through Pathology: Initiation of the Global Health
      Pathology Network.

PMID- 29635994
TI  - Multifaceted Roles of Autophagy in Health and Disease.

PMID- 29635995
TI  - Reconsidering Forced Labels: Outcomes of Sexual Assault Survivors Versus Victims
      (and Those Who Choose Neither).
AB  - The goal of the current study was to assess the effects of self-labeling on
      attitudes related to victim- and self-blaming and self-compassion outcomes in 85
      participants (75 women, 10 men) who have experienced sexual assault. Participants
      classified themselves as either a survivor, victim, or neither survivor nor
      victim of sexual assault. Regardless of self-classification, groups did not
      differ in victim-blaming (rape myth acceptance), self-blaming, or levels of self
      compassion. Implications for language and forced labels of those who have
      experienced sexual assault are discussed.

PMID- 29635996
TI  - Increased flexibility, pain reduction and unaltered levels of IL-10 and CD11b +
      lymphocytes in patients with systemic lupus erythematosus were associated with
      kinesiotherapy.
AB  - The effect of physical activity on the immune system is still poorly understood
      in cases of systemic lupus erythematosus (SLE). Therefore, our aim was to
      investigate differences in the serum levels of cytokines (IL-2, IL-5, IL-6, IL-8,
      IL-10 and TNF-alpha) and the numbers of CD11b + and CXCR2 + neutrophils and
      lymphocytes in women with SLE undergoing drug treatment, without ( n = 9) or with
      ( n = 5) 4 months of kinesiotherapy. Parameters related to functional capacity
      were also analyzed. In the case of the patients who were not submitted to
      kinesiotherapy, there were reductions in the levels of IL-5, IL-6 and IL-10, and
      an increase in the number of CD11b + leukocytes, in addition to an increase in
      abdominal circumference after the monitoring time. Patients submitted to
      kinesiotherapy did not present changes in serum cytokines or in the numbers of
      CD11b + and CXCR2 + neutrophils and lymphocytes, but there were increases of
      flexibility and strength, as well as a reduction in pain sensation after the
      monitoring time. In conclusion, kinesiotherapy was able to increase flexibility
      and reduce pain in SLE patients without influencing immune parameters.

PMID- 29635997
TI  - Natural history of longitudinally extensive transverse myelitis in 35 Hispanic
      patients with systemic lupus erythematosus: good short-term functional outcome
      and paradoxical increase in long-term mortality.
AB  - Background and objective Acute transverse myelitis (TM) is an infrequent
      neurological complication of systemic lupus erythematosus (SLE). Short-term
      outcome varies widely between cohorts. Little is known about the epidemiology and
      long-term functional outcome of TM associated to SLE. Methods Patients with SLE
      and acute TM were identified during hospital admission, visits to the Emergency
      Room or the Neurology Outpatient Clinic. We evaluated ambispectively those
      patients with SLE presenting with clinical myelopathy and corroborated with
      spinal MRI. Cases were divided as partial (non-paralyzing) or complete
      (paralyzing). We determined long-term functional outcome as well as mortality in
      those patients with follow-up periods of at least five years. Results We
      identified 35 patients (partial, n = 15; complete, n = 20) in which complete
      clinical and imaging data were available (26 with follow-up >= 5 years). Patients
      with complete TM were significantly older than those with partial forms. Positive
      antiphospholipid antibodies were observed in 80% of patients, suggesting a
      possible mechanistical role. Surprisingly, functional recovery at one year was in
      general good; however, we observed a five-year mortality of 31% because of sepsis
      (in 10 cases) or pulmonary embolism (in one case). Conclusions Short-term outcome
      of SLE-related TM is generally good, and recurrence rate is low. However, we
      observed a long-term fatality rate of 31% for reasons unrelated to TM, suggesting
      that TM is a manifestation of severe immune dysregulation and a predictor of
      severity and mortality in patients with SLE.

PMID- 29635998
TI  - Combined mepacrine-hydroxychloroquine treatment in patients with systemic lupus
      erythematosus and refractory cutaneous and articular activity.
AB  - Aim The aim of this study was to evaluate the clinical response to combined
      therapy with hydroxychloroquine and mepacrine in patients with systemic lupus
      erythematosus and refractory joint and/or skin disease. Methods Mepacrine was
      added to 46 systemic lupus erythematosus patients unresponsive to treatment with
      the following drug combinations: hydroxychloroquine + prednisone +
      immunosuppressive drugs ( n = 24), hydroxychloroquine + prednisone ( n = 16),
      hydroxychloroquine + prednisone + retinoids ( n = 2), hydroxychloroquine alone (
      n = 1), hydroxychloroquine + one immunosuppressive drug ( n = 1),
      hydroxychloroquine + prednisone + one immunosuppressive drug + belimumab ( n = 1)
      or hydroxychloroquine + prednisone + belimumab ( n = 1). The outcome variable was
      the clinical response, either complete or partial, based on clinical judgement.
      The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) and the
      Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score were
      additionally used. Results A total of 91% patients showed complete/partial
      response, with similar rates among those with joint or skin disease. In patients
      with cutaneous activity, a statistically significant decrease in the CLASI was
      seen. There also was a statistically significant decrease in the SLEDAI. The mean
      daily dose of prednisone decreased from 5.8 to 3.4 mg/d ( p = 0.001). Prednisone
      could be discontinued in 20% of patients. No serious adverse events were seen.
      Smoking was the only predictor of complete response. Conclusion In the setting of
      refractory skin and/or joint disease, the addition of mepacrine to previous
      therapy including hydroxychloroquine was safe and effective in reducing disease
      activity and decreasing prednisone doses. The fact that smokers responded better
      opens the door to further studying the combination of mepacrine
      hydroxychloroquine as a first-line therapy in such patients.

PMID- 29635999
TI  - Microthrombotic renal involvement in an SLE patient with concomitant catastrophic
      antiphospholipid syndrome: the beneficial effect of rituximab treatment.
AB  - Antiphospholipid syndrome is characterized by multiple arterial and/or venous
      thrombotic events, recurrent fetal losses in the presence of antiphospholipid
      antibodies (aPL). Catastrophic antiphospholipid syndrome is a life-threatening,
      rare subset of antiphospholipid syndrome when the thrombotic events affect at
      least three organs, and clinical manifestations develop simultaneously or within
      a week. Diagnostically, small vessel occlusions can be detected by histopathology
      in the presence of aPL. Our case report describes an 18-year-old man who has been
      treated for antiphospholipid syndrome associated with systemic lupus
      erythematosus (SLE) since 2011. The clinical findings were dominated by recurrent
      deep vein thrombosis, and severe proteinuria caused by lupus nephritis,
      accompanied by mild serological and laboratory findings. The patient was
      hospitalized in March 2014 because of severe thrombocytopenia and infective
      diarrhoea. At this time the renal functions deteriorated rapidly. Simultaneously,
      left upper extremity paresis was observed; computed tomography showed ischaemic
      lesions in the territory of the middle cerebral artery. Abdominal discomfort and
      pain occurred. On computed tomography scan ischaemic lesions were seen in the
      spleen, the right kidney and the coeliac trunk. Laboratory and serological
      findings verified the presence of aPL and anti-DNA antibodies, anaemia and
      thrombocytopenia. Based on the above-mentioned clinical and laboratory findings,
      the diagnosis of catastrophic antiphospholipid syndrome was established.
      Anticoagulation, corticosteroids and plasma exchange treatment, as well as
      haemodiafiltration were initiated. Although the thrombotic cascade decelerated
      following these interventions, we could not see an improvement in the renal
      function. Rituximab treatment was started, leading to a significant improvement
      in renal function. After 5 weeks of treatment the patient was discharged from
      hospital.

PMID- 29636000
TI  - Disjunct distribution and distinct intraspecific diversification of Eothenomys
      melanogaster in South China.
AB  - BACKGROUND: South China encompasses complex and diverse landforms, giving rise to
      high biological diversity and endemism from the Hengduan Mountains to Taiwan
      Island. Many species are widely distributed across South China with similar
      disjunct distribution patterns. To explore the causes of these disjunct
      distribution patterns and their genetic consequences, we investigated the endemic
      species Pere David's Chinese Vole (Eothenomys melanogaster) by integrating
      geological and ecological factors. We analysed the genetic structure and
      divergence time of E. melanogaster based on fast-evolving mitochondrial and
      nuclear markers using Bayesian trees and coalescent species tree approaches.
      Historical scenarios of distribution range and demography were reconstructed
      based on spatial interpolations of genetic diversity and distance, extended
      Bayesian skyline plots, phylogeographic diffusion analysis, and ecological niche
      modelling (ENM) during different periods. We also assessed the relationships
      between geographical distance/ecological vicariance and genetic distance
      (isolation by distance, IBD; isolation by environment, IBE). RESULTS: The genetic
      analysis revealed three deeply divergent clades-Southeast, Southwest and Central
      clades, centred on the Wuyi Mountains, the Yunnan-Guizhou Plateau (YGP) and the
      mountains around the Sichuan Basin, respectively-that have mostly developed since
      the Pleistocene. IBD played an important role in early divergence, and geological
      events (sedimentation of plains and linking of palaeo-rivers) and IBE further
      reinforced genetic differentiation. ENM shows the importance of suitable habitats
      and elevations. CONCLUSIONS: Our results suggest that the primary cause of the
      disjunct distribution in E. melanogaster is the high dependence on middle-high
      altitude habitat in the current period. Mountains in the occurence range have
      served as "sky islands" for E. melanogaster and hindered gene flow. Pleistocene
      climatic cycles facilitated genetic admixture in cold periods and genetic
      diversification in warm periods for inland clades. During cold periods, these
      cycles led to multiple colonization events between the mainland and Taiwan and
      erased genetic differentiation.

PMID- 29636001
TI  - Genome-wide (ChIP-seq) identification of target genes regulated by BdbZIP10
      during paraquat-induced oxidative stress.
AB  - BACKGROUND: bZIP transcription factors play a significant role in many aspects of
      plant growth and development and also play critical regulatory roles during plant
      responses to various stresses. Overexpression of the Brachypodium bZIP10
      (Bradi1g30140) transcription factor conferred enhanced oxidative stress tolerance
      and increased viability when plants or cells were exposed to the herbicide
      paraquat. To gain a better understanding of genes involved in bZIP10 conferred
      oxidative stress tolerance, chromatin immunoprecipitation followed by high
      throughput sequencing (ChIP-Seq) was performed on BdbZIP10 overexpressing plants
      in the presence of oxidative stress. RESULTS: We identified a transcription
      factor binding motif, TGDCGACA, different from most known bZIP TF motifs but with
      strong homology to the Arabidopsis zinc deficiency response element. Analysis of
      the immunoprecipitated sequences revealed an enrichment of gene ontology groups
      with metal ion transmembrane transporter, transferase, catalytic and binding
      activities. Functional categories including kinases and phosphotransferases,
      cation/ion transmembrane transporters, transferases (phosphorus-containing and
      glycosyl groups), and some nucleoside/nucleotide binding activities were also
      enriched. CONCLUSIONS: Brachypodium bZIP10 is involved in zinc homeostasis, as it
      relates to oxidative stress.

PMID- 29636002
TI  - Analyses of starch biosynthetic protein complexes and starch properties from
      developing mutant rice seeds with minimal starch synthase activities.
AB  - BACKGROUND: Starch is the major component of cereal grains and is composed of
      essentially linear amylose and highly branched amylopectin. The properties and
      composition of starch determine the use and value of grains and their products.
      Starch synthase (SS) I, SSIIa, and SSIIIa play central roles in amylopectin
      biosynthesis. These three SS isozymes also affect seed development, as complete
      loss of both SSI and SSIIIa under reduced SSIIa activity in rice lead to
      sterility, whereas presence of minimal SSI or SSIIIa activity is sufficient for
      generating fertile seeds. SSs, branching enzymes, and/or debranching enzymes form
      protein complexes in cereal. However, the relationship between starch properties
      and the formation of protein complexes remain largely unknown. To better
      understand this phenomenon, properties of starch and protein complex formation
      were analyzed using developing mutant rice seeds (ss1 L /ss2a L /ss3a) in which
      all three major SS activities were reduced. RESULTS: The SS activity of ss1 L
      /ss2a L /ss3a was 25%-30% that of the wild-type. However, the grain weight of ss1
      L /ss2a L /ss3a was 89% of the wild-type, 55% of which was starch, showing
      considerable starch synthesis. The reduction of soluble SS activity in ss1 L
      /ss2a L /ss3a resulted in increased levels of ADP-glucose pyrophosphorylase and
      granule-bound starch synthase I, which are responsible for substrate synthesis
      and amylose synthesis, respectively. Together, these features led to an increase
      in apparent amylose content (34%) in ss1 L /ss2a L /ss3a compared with wild-type
      (20%). Gel filtration chromatography of the soluble proteins in ss1 L /ss2a L
      /ss3a showed that the majority of the starch biosynthetic enzymes maintained the
      similar elution patterns as wild-type, except that the amounts of high-molecular
      weight SSI (> 300 kDa) were reduced and SSIIa of approximately 200-300 kDa were
      present instead of those > 440 kDa, which predominate in wild-type. Immuno
      precipitation analyses suggested that the interaction between the starch
      biosynthetic enzymes maybe reduced or weaker than in wild-type. CONCLUSIONS:
      Although major SS isozymes were simultaneously reduced in ss1 L /ss2a L /ss3a
      rice, active protein complexes were formed with a slightly altered pattern,
      suggesting that the assembly of protein complexes may be complemented among the
      SS isozymes. In addition, ss1 L /ss2a L /ss3a maintained the ability to
      synthesize starch and accumulated less amylopectin and more amylose in starch.

PMID- 29636004
TI  - Dose selection of central or peripheral administration of sufentanil affect
      opioid induced cough?: a prospective, randomized, controlled trial.
AB  - BACKGROUND: Opioid-induced cough (OIC) is one of the most common complications of
      opioids during anesthesia induction. This study was designed to assess the
      incidence of OIC mediated by different intravenous route. METHODS: A total of
      102(ASA I-II) scheduled for elective surgery under general anesthesia were
      randomly allocated into two groups: central vein group (group CV, n = 51) and
      peripheral vein group (group PV, n = 51). The incidence, onset time and severity
      of OIC were evaluated within 1 min just after sufentanil injection during
      induction. Meanwhile, heart rate (HR) and blood pressure (BP) were also recorded
      to assess the hemodynamic changes. RESULTS: The incidence of OIC was 10/51
      (20.4%) in group CV and 16/51 (32%) in group PV, patients received central venous
      administration of sufentanil experienced less OIC compared with those injected by
      peripheral venous route (P < 0.05), as well as a significantly lower incidence of
      severe OIC (P < 0.05). Nevertheless, the onset of OIC and hemodynamic data were
      comparable between two groups (P > 0.05). CONCLUSION: Our study indicates that
      sufentanil administration by central venous route reduces the incidence and
      severity of OIC, but without significant changes in hemodynamic status. TRIAL
      REGISTRATION: Chinese Clinical Trial Registry with registration number ChiCTR-IOR
      15006075 . Registered 28 February 2015.

PMID- 29636003
TI  - Malaria parasites of long-tailed macaques in Sarawak, Malaysian Borneo: a novel
      species and demographic and evolutionary histories.
AB  - BACKGROUND: Non-human primates have long been identified to harbour different
      species of Plasmodium. Long-tailed macaques (Macaca fascicularis), in particular,
      are reservoirs for P. knowlesi, P. inui, P. cynomolgi, P. coatneyi and P. fieldi.
      A previous study conducted in Sarawak, Malaysian Borneo, however revealed that
      long-tailed macaques could potentially harbour novel species of Plasmodium based
      on sequences of small subunit ribosomal RNA and circumsporozoite genes. To
      further validate this finding, the mitochondrial genome and the apicoplast
      caseinolytic protease M genes of Plasmodium spp. were sequenced from 43 long
      tailed macaque blood samples. RESULTS: Apart from several named species of
      malaria parasites, long-tailed macaques were found to be potentially infected
      with novel species of Plasmodium, namely one we refer to as "P. inui-like." This
      group of parasites bifurcated into two monophyletic clades indicating the
      presence of two distinct sub-populations. Further analyses, which relied on the
      assumption of strict co-phylogeny between hosts and parasites, estimated a
      population expansion event of between 150,000 to 250,000 years before present of
      one of these sub-populations that preceded that of the expansion of P. knowlesi.
      Furthermore, both sub-populations were found to have diverged from a common
      ancestor of P. inui approximately 1.5 million years ago. In addition, the
      phylogenetic analyses also demonstrated that long-tailed macaques are new hosts
      for P. simiovale. CONCLUSIONS: Malaria infections of long-tailed macaques of
      Sarawak, Malaysian Borneo are complex and include a novel species of Plasmodium
      that is phylogenetically distinct from P. inui. These macaques are new natural
      hosts of P. simiovale, a species previously described only in toque monkeys
      (Macaca sinica) in Sri Lanka. The results suggest that ecological factors could
      affect the evolution of malaria parasites.

PMID- 29636005
TI  - Nuancing the role of social skills- a longitudinal study of early maternal
      psychological distress and adolescent depressive symptoms.
AB  - BACKGROUND: Social skills might play an important role for the relationship
      between maternal psychological distress and subsequent development of depressive
      symptoms. The majority perspective is that social skills is adaptive and
      protective, but there is a need to also highlight the potential maladaptive
      effect of social skills in some settings or for some sub groups. The current
      study examined the longitudinal interplay between maternal-reported psychological
      distress in early childhood (age 1.5), and offspring reports on social skills and
      depressive symptoms in early (age 12.5) and middle adolescence (age 14.5).
      METHODS: We used data from the Tracking Opportunities and Problems Study (TOPP),
      a community-based longitudinal study following Norwegian families to examine
      direct links and interactions between early maternal distress (measured with the
      Hopkins Symptom Checklist) and early adolescent offspring social skills (measured
      with the Social Skills Rating System) and middle adolescent depressive symptoms
      (measured with the Moods and Feelings Questionnaire) in 370 families (in total
      740 mothers and adolescents). RESULTS: Exposure to childhood maternal distress
      predicted offspring depressive symptoms in middle adolescence. Higher social
      skills in early adolescence predicted lower levels of depressive symptoms for
      girls, but not for boys, in middle adolescence. An interaction effect was found
      in which adolescents exposed to early maternal distress who reported high social
      skills in early adolescence had the highest level of depressive symptoms in
      middle adolescence. CONCLUSIONS: The findings highlight the nuances in the role
      of social skills for adolescent depressive symptoms - having the potential to be
      both adaptive as well as maladaptive for some subgroups (those experiencing
      maternal psychological distress). This has important implications for social
      skill programs.

PMID- 29636007
TI  - DNA methylation profiles correlated to striped bass sperm fertility.
AB  - BACKGROUND: Striped bass (Morone saxatilis) spermatozoa are used to fertilize in
      vitro the eggs of white bass (M. chrysops) to produce the preferred hybrid for
      the striped bass aquaculture industry. Currently, only one source of domestic
      striped bass juveniles is available to growers that is not obtained from wild
      caught parents and is thus devoid of any genetic improvement in phenotypic traits
      of importance to aquaculture. Sperm epigenetic modification has been predicted to
      be associated with fertility, which could switch genes on and off without
      changing the DNA sequence itself. DNA methylation is one of the most common
      epigenetic modification types and changes in sperm epigenetics can be correlated
      to sub-fertility or infertility in male striped bass. The objective of this study
      was to find the differentially methylated regions (DMRs) between high-fertility
      and sub-fertility male striped bass, which could potentially regulate the
      fertility performance. RESULTS: In our present study, we performed DNA
      methylation analysis of high-fertility and sub-fertility striped bass spermatozoa
      through MBD-Seq methods. A total of 171 DMRs were discovered in striped bass
      sperm correlated to fertility. Based on the annotation of these DMRs, we
      conducted a functional classification analysis and two important groups of genes
      including the WDR3/UTP12 and GPCR families, were discovered to be related to
      fertility performance of striped bass. Proteins from the WDR3/UTP12 family are
      involved in forming the sperm flagella apparatus in vertebrates and GPCRs are
      involved in hormonal signaling and regulation of tissue development,
      proliferation and differentiation. CONCLUSIONS: Our results contribute insights
      into understanding the mechanism of fertility in striped bass, which will provide
      powerful tools to maximize reproductive efficiencies and to identify those males
      with superior gametes for this important aquaculture species.

PMID- 29636006
TI  - Genomic architecture of haddock (Melanogrammus aeglefinus) shows expansions of
      innate immune genes and short tandem repeats.
AB  - BACKGROUND: Increased availability of genome assemblies for non-model organisms
      has resulted in invaluable biological and genomic insight into numerous
      vertebrates, including teleosts. Sequencing of the Atlantic cod (Gadus morhua)
      genome and the genomes of many of its relatives (Gadiformes) demonstrated a
      shared loss of the major histocompatibility complex (MHC) II genes 100 million
      years ago. An improved version of the Atlantic cod genome assembly shows an
      extreme density of tandem repeats compared to other vertebrate genome assemblies.
      Highly contiguous assemblies are therefore needed to further investigate the
      unusual immune system of the Gadiformes, and whether the high density of tandem
      repeats found in Atlantic cod is a shared trait in this group. RESULTS: Here, we
      have sequenced and assembled the genome of haddock (Melanogrammus aeglefinus) - a
      relative of Atlantic cod - using a combination of PacBio and Illumina reads.
      Comparative analyses reveal that the haddock genome contains an even higher
      density of tandem repeats outside and within protein coding sequences than
      Atlantic cod. Further, both species show an elevated number of tandem repeats in
      genes mainly involved in signal transduction compared to other teleosts. A
      characterization of the immune gene repertoire demonstrates a substantial
      expansion of MCHI in Atlantic cod compared to haddock. In contrast, the Toll-like
      receptors show a similar pattern of gene losses and expansions. For the NOD-like
      receptors (NLRs), another gene family associated with the innate immune system,
      we find a large expansion common to all teleosts, with possible lineage-specific
      expansions in zebrafish, stickleback and the codfishes. CONCLUSIONS: The
      generation of a highly contiguous genome assembly of haddock revealed that the
      high density of short tandem repeats as well as expanded immune gene families is
      not unique to Atlantic cod - but possibly a feature common to all, or most,
      codfishes. A shared expansion of NLR genes in teleosts suggests that the NLRs
      have a more substantial role in the innate immunity of teleosts than other
      vertebrates. Moreover, we find that high copy number genes combined with variable
      genome assembly qualities may impede complete characterization of these genes,
      i.e. the number of NLRs in different teleost species might be underestimates.

PMID- 29636008
TI  - Community health education improves child health care in Rural Western China.
AB  - BACKGROUND: Rural infant growth failure has been highlighted as a priority for
      action in China's national nutrition and child development policies. The aim of
      this paper was to evaluate the effect of community-based intervention project on
      child feeding, child health care and child growth. METHODS: From 2001 to 2005,
      UNICEF and China's Ministry of Health worked together to develop holistic
      strategies for child health care. All the interventions were implemented through
      the three-tier (county-township-village) rural health care network.In this study,
      34 counties were included in both surveys in 2001 and 2005. Among these 34
      counties, nine were subjected to the intervention and 25 counties were used as
      controls. In nine intervention counties, leaflets containing information of
      supplemental feeding of infants and young children were printed and distributed
      to women during hospital delivery or visit to newborn by village doctors. Two
      cross-sectional surveys were both conducted from July to early September in 2001
      and 2005. We calculated Z-scores of height-for-age (HAZ), weight-for-age (WAZ)
      and weight-for-height (WHZ), with the new WHO growth standard. HAZ < - 2 was
      defined as stunting, WAZ < - 2 was defined as underweight, and WHZ < - 2 was
      defined as wasting. RESULTS: Following the four-year study period, the parents in
      the intervention group showed significantly better infant and young child feeding
      practices and behaviors of child care than did their control group counterparts.
      In addition, all three anthropometric indicators in 2005 in the intervention
      group were better than in the control, with stunting 4.9% lower (p < 0.001),
      underweight 2.2% lower (p < 0.001), and wasting 1.0% lower (p < 0.05).
      CONCLUSIONS: We concluded that the health care education intervention embed in
      government had the potential to be successfully promoted in rural western China.

PMID- 29636009
TI  - Genome and transcriptome of the natural isopropanol producer Clostridium
      beijerinckii DSM6423.
AB  - BACKGROUND: There is a worldwide interest for sustainable and environmentally
      friendly ways to produce fuels and chemicals from renewable resources. Among
      them, the production of acetone, butanol and ethanol (ABE) or Isopropanol,
      Butanol and Ethanol (IBE) by anaerobic fermentation has already a long industrial
      history. Isopropanol has recently received a specific interest and the best
      studied natural isopropanol producer is C. beijerinckii DSM 6423 (NRRL B-593).
      This strain metabolizes sugars into a mix of IBE with only low concentrations of
      ethanol produced (< 1 g/L). However, despite its relative ancient discovery, few
      genomic details have been described for this strain. Research efforts including
      omics and genetic engineering approaches are therefore needed to enable the use
      of C. beijerinckii as a microbial cell factory for production of isopropanol.
      RESULTS: The complete genome sequence and a first transcriptome analysis of C.
      beijerinckii DSM 6423 are described in this manuscript. The combination of MiSeq
      and de novo PacBio sequencing revealed a 6.38 Mbp chromosome containing 6254
      genomic objects. Three Mobile Genetic Elements (MGE) were also detected: a linear
      double stranded DNA bacteriophage (phi6423) and two plasmids (pNF1 and pNF2)
      highlighting the genomic complexity of this strain. A first RNA-seq
      transcriptomic study was then performed on 3 independent glucose fermentations.
      Clustering analysis allowed us to detect some key gene clusters involved in the
      main life cycle steps (acidogenesis, solvantogenesis and sporulation) and
      differentially regulated among the fermentation. These putative clusters included
      some putative metabolic operons comparable to those found in other reference
      strains such as C. beijerinckii NCIMB 8052 or C. acetobutylicum ATCC 824.
      Interestingly, only one gene was encoding for an alcohol dehydrogenase converting
      acetone into isopropanol, suggesting a single genomic event occurred on this
      strain to produce isopropanol. CONCLUSIONS: We present the full genome sequence
      of Clostridium beijerinckii DSM 6423, providing a complete genetic background of
      this strain. This offer a great opportunity for the development of dedicated
      genetic tools currently lacking for this strain. Moreover, a first RNA-seq
      analysis allow us to better understand the global metabolism of this natural
      isopropanol producer, opening the door to future targeted engineering approaches.

PMID- 29636010
TI  - Metformin restores electrophysiology of small conductance calcium-activated
      potassium channels in the atrium of GK diabetic rats.
AB  - BACKGROUND: Small conductance calcium-activated potassium channels (SK channels)
      play a critical role in action potential repolarization in cardiomyocytes.
      Recently, the potential anti-arrhythmic effect of metformin in diabetic patients
      has been recognized, yet the underlying mechanism remains elusive. METHODS:
      Diabetic Goto-Kakizaki (GK) rats were untreated or treated with metformin (300
      mg/kg/day) for 12 weeks, and age-matched Wistar rats were used as control (n = 6
      per group). Electrocardiography, Hematoxylin-eosin staining and Masson's trichome
      staining were performed to assess cardiac function, histology and fibrosis. The
      expression levels of the SK channels in the myocardium were determined by real
      time PCR and Western blotting. The electrophysiology of the SK channels in the
      cardiomyocytes isolated from the three groups of rats was examined by patch clamp
      assay, with specific blockade of the SK channels with apamin. RESULTS: Metformin
      treatment significantly reduced cardiac fibrosis and alleviated arrhythmia in the
      diabetic rats. In the atrial myocytes from control, GK and metformin-treated GK
      rats, the expression of KCa2.2 (SK2 channel) was down-regulated and the
      expression of KCa2.3 (SK3 channel) was up-regulated in the atrium of GK rats as
      compared with that of control rats, and metformin reversed diabetes-induced
      alterations in atrial SK channel expression. Moreover, patch clamp assay revealed
      that the SK current was markedly reduced and the action potential duration was
      prolonged in GK atrial myocytes, and the SK channel function was partially
      restored in the atrial myocytes from metformin-treated GK rats. CONCLUSIONS: Our
      data suggests an involvement of the SK channels in the development of arrhythmia
      under diabetic conditions, and supports a potential beneficial effect of
      metformin on atrial electrophysiology.

PMID- 29636011
TI  - Prospective investigation of intravenous patient-controlled analgesia with
      hydromorphone or sufentanil: impact on mood, opioid adverse effects, and
      recovery.
AB  - BACKGROUND: Radical surgery for colorectal cancer, associated with moderate to
      severe postoperative pain, needs multimodal analgesia with opioid for analgesia.
      Despite considerable advancements, the psychological implications and other side
      effects with opioid remain substantially unresolved. This study aimed to
      investigate the impact on mood, side effects relative to opioid, and recovery of
      the patients with hydromorphone or sufentanil intravenous patient-controlled
      analgesia (IV-PCA) in a multimodal perioperative analgesia regimen undergoing
      radical surgery for colorectal cancer. METHODS: Eighty patients undergoing
      elective laparoscopic or open radical surgery for colorectal cancer under general
      anesthesia were randomized to receive postoperative IV-PCA with either sufentanil
      (group S) or hydromorphone (group H). All patients received additionally
      flurbiprofen axetil 50 mg 30 min before the end of surgery and wound infiltration
      with 10 ml of 0.75% ropivacaine at the end of surgery. The primary endpoint was
      mood changes at 48 and 96 h after surgery. The secondary endpoints were the
      incidence of opioid-related adverse effects, recovery results and patient
      satisfaction after surgery. RESULTS: Seventy-two patients completed the study
      finally. There were no significant differences between the two groups with
      respect to preoperative parameters, surgical and anesthetic characteristics (P >
      0.05). No obvious significant differences were observed in VAS score (at rest and
      during mobilization) and rescue analgesics use (P > 0.05). Compared with group S,
      the anger scores in the group H at 48 h and 96 h after surgery were significantly
      lower (P = 0.012 and 0.005; respectively), but the incidences of pruritus and
      nausea were higher (P = 0.028 and 0.008; respectively). There were no significant
      differences in the incidences of vomiting, respiratory depression, dizziness,
      Ramsay score, and hemodynamic changes between the two groups (P > 0.05).
      Moreover, there were no significant differences in the time to gastrointestinal
      recovery, time to drainage tube removal, time to walk, hospital stay after
      surgery and patient satisfaction between the two groups (P > 0.05). CONCLUSIONS:
      Under the similar analgesia effect with different opoiods postoperatively,
      hydromorphone IV-PCA resulted in an improved mood, however, a higher occurrence
      of pruritus and nausea while compared to sufentanil IV-PCA in a multimodal
      perioperative analgesia regimen. Both regimens of opioid with IV-PCA may serve as
      promising candidates for good postoperative pain management, and provide with
      similar postoperative recovery for the patients undergoing radical surgery for
      colorectal cancer. TRIAL REGISTRATION: This study was registered with the Chinese
      Clinical Trial Registry on September 20, 2015 (URL: http://www.chictr.org.cn .
      Registry number: ChiCTR-IPR-15007112).

PMID- 29636012
TI  - Trends in the contemporary incidence of colorectal cancer and patient
      characteristics in the United Kingdom: a population-based cohort study using The
      Health Improvement Network.
AB  - BACKGROUND: Cancer registry data show that survival of colorectal cancer (CRC) in
      the United Kingdom is poor compared with other European countries and the United
      States, yet these data sources lack information on patient comorbidities and
      medication use, which could help explain these differences. METHODS: Among
      individuals aged 40-89 years in The Health Improvement Network (2000-2014), we
      identified first ever cases of CRC and calculated incidence rates with 95%
      confidence intervals (CIs). For CRC cases and non-cases in two separate calendar
      years (2002 and 2014), we evaluated patient demographics, lifestyle factors,
      comorbidities and medication use and bowel screening. RESULTS: The incidence of
      CRC remained relatively constant across the study period; incidence rates per
      10,000 person-years (95% CIs) were 9.27 (8.59-1.01) in 2000, 10.65 (10.15-11.18)
      in 2007 and 8.37 (7.93-8.83) in 2014. Incidence rates per 10,000 person-years
      were higher in men than women at 11.44 (95% CI: 10.35-12.66) vs. 7.40 (95% CI:
      6.59-8.32) in 2000, and 9.39 (95% CI: 8.74-10.10) vs. 7.38 (95% CI: 6.81-8.00) in
      2014. An increase was seen in the proportion of CRC cases diagnosed at age < 60
      years. In 2002, 3.5% of CRC cases were diagnosed at age 40-49 compared with 5.1%
      in 2014 (p = 0.064). Similarly, in 2002, 12.5% were diagnosed at age 50-59 years
      compared with 16.2% in 2014 (p = 0.002). Between 2002 and 2014, previous bowel
      screening increased in both CRC cases (+ 10.6%) and non-cases (+ 9.7%)(p < 0.001
      for both groups). Greater rises in the following were seen among CRC cases
      compared with non-cases: diabetes (+ 9.3% vs. + 3.3%; p < 0.001 for both),
      obesity (+ 14.5% vs. + 10.1%; p < 0.001 for both), hypertension (+ 8.3% vs. +
      3.6%; p < 0.001 for both), atrial fibrillation (+ 2.6% [p < 0.01] vs. + 0.3% [p <
      0.001]), and use of proton pump inhibitors (+ 11.5% vs. + 9.0%), anti
      hypertensives (+ 9.9% vs. + 1.4%) and warfarin (+ 3.2% vs. + 0.4%); p < 0.001 for
      CRC cases and non-cases with respect to each medication. CONCLUSIONS: CRC
      incidence has remained relatively stable in the UK over the last decade. The
      increased prevalence of some comorbidities and medications among CRC cases should
      be considered when evaluating patterns in CRC survival.

PMID- 29636013
TI  - Education and micronutrient deficiencies: an ecological study exploring
      interactions between women's schooling and children's micronutrient status.
AB  - BACKGROUND: Formal education can be a nutrition-sensitive intervention that
      supports the scale-up and impact of nutrition-specific actions. Maternal
      education has long been linked to child survival, growth, and development while
      adult earnings and nutrition are tied to years in school as a child. However,
      less is known about the relationship between maternal education and the
      micronutrient status of children, women and the general population. METHODS:
      Using country-level data and an ecological study design, we explored the global
      associations between women's educational attainment and: a) anemia and vitamin A
      deficiency (VAD) in children aged 6-59 months; b) anemia in non-pregnant women;
      and c) zinc deficiency, urinary iodine excretion (UIE), and the proportion of
      infants protected against iodine deficiency in the general population Cross
      sectional relationships (2005-2013) were assessed using linear regression models.
      RESULTS: Percentage of women without schooling was negatively associated with all
      outcomes. Number of years of schooling among women was positively associated with
      all outcomes except for UIE and the proportion of infants protected against
      iodine deficiency. Income level was a significant effect modifier of the effect
      of years of women's schooling on child anemia as well as of the proportion of
      women without formal education on zinc deficiency in the population. The
      relationship was strongest in low-income countries for child anemia, and was not
      significant in upper middle-income countries. For zinc deficiency, the
      relationship was not significant in low or lower middle income countries, which
      may suggest that a minimum threshold of resources needs to be reached before
      education can influence zinc status. CONCLUSIONS: While relationships between
      maternal schooling and micronutrient outcomes vary around the globe, more
      schooling is generally linked to lower rates of deficiency. These findings draw
      policy-relevant connections between formal education and anemia and micronutrient
      status globally. It is necessary to examine the mechanisms through which this
      relationship may be working at both household and country level.

PMID- 29636014
TI  - Genetic loci for resistance to podocyte injury caused by the tensin2 gene
      deficiency in mice.
AB  - BACKGROUND: Tensin2 is a focal adhesion-localized multidomain protein expressed
      in various tissues, and its dysfunction leads to alterations in podocytes.
      However, these podocyte-related manifestations are dependent on murine strain.
      Tensin2 dysfunction results in susceptible strains developing podocyte foot
      process effacement and massive albuminuria, whereas podocytes in resistant
      strains remain almost intact. In our previous studies, quantitative trait loci
      analysis and congenic analysis using resistant C57BL/6J and susceptible ICGN mice
      identified a modifier locus associated with podocyte injury caused by tensin2
      dysfunction on chromosome 2. However, the effect of this modifier locus on
      chromosome 2 is insufficient to explain the resistance of C57BL/6J mice to
      tensin2 dysfunction, indicating the existence of other modifier genes. RESULTS:
      Whereas previous studies focused on the severity of chronic kidney disease, the
      present study focused on podocyte injury. We performed a genome-wide linkage
      analysis of backcrosses between two tensin2-deficient mouse strains, B6.ICGN-Tns2
      nph and FVB.ICGN-Tns2 nph , and detected a novel major modifier locus on
      chromosome 10. The combined effect of the C57BL/6J alleles of the two loci on
      chromosomes 2 and 10 reduced the urinary albumin excretion caused by tensin2
      dysfunction to a level comparable to that of C57BL/6J mice. CONCLUSIONS: These
      data indicate that the resistance to podocyte injury caused by tensin2
      dysfunction is mainly produced by the effects of the modifier genes on the two
      loci. The identification of these modifier genes is expected to help elucidate
      the mechanism underlying podocyte injury.

PMID- 29636015
TI  - MicroRNA expression profiles of bovine monocyte-derived macrophages infected in
      vitro with two strains of Streptococcus agalactiae.
AB  - BACKGROUND: MicroRNAs (miRNAs) are short, non-coding RNAs that regulate gene
      expression at the post-transcriptional level and play a key role in the control
      of innate and adaptive immune responses. For a subclinical infection such as
      bovine streptococcal mastitis, early detection is a great challenge, and miRNA
      profiling could potentially assist in the diagnosis and contribute to the
      understanding of the pathogenicity and defense mechanisms. We have examined the
      miRNA repertoire and the transcript level of six key immune genes [tumor necrosis
      factor alpha (TNFalpha), interleukin-1 beta (IL-1beta), interleukin-6 (IL-6),
      interleukin-8 (IL-8), interleukin-10 (IL-10) and transforming growth factor beta
      1 (TGFbeta1)] during the early phase response of bovine immature macrophages to
      in vitro infection with live Streptococcus agalactiae. Next generation sequencing
      of small RNA libraries from 20 cultures of blood monocyte-derived macrophages
      exposed to either one of two sequence types of S. agalactiae (ST103 or ST12) for
      6 h in vitro and unchallenged controls was performed. RESULTS: Analyzes of over
      356 million high quality sequence reads, revealed differential expression of 17
      and 44 miRNAs (P < 0.05) in macrophages infected with ST103 and ST12,
      respectively, versus unchallenged control cultures. We also identified the
      expression of 31 potentially novel bovine miRNAs. Pathway analysis of the
      differentially regulated miRNAs and their predicted target genes in the
      macrophages infected with ST12 revealed significant enrichment for inflammatory
      response and apoptosis, while significant enrichment for integrin and GABA
      signaling were found in ST103 infected macrophages. Furthermore, both bacterial
      strains regulated miRNAs involved in the alternative activation of macrophages.
      The transcript levels of TNF-alpha, IL-1beta, IL-6, IL-8 and IL-10 were
      significantly up-regulated by both bacterial strains, however the expression of
      TGFbeta1 was significantly down-regulated only by ST12. CONCLUSIONS: Our study
      identified pathogen-induced differential regulation of miRNAs controlling
      inflammation and polarization in bovine macrophages. This implies that miRNAs
      have potential to serve as biomarkers for early detection of bacterial infection.

PMID- 29636016
TI  - Machine learning classification of first-episode schizophrenia spectrum disorders
      and controls using whole brain white matter fractional anisotropy.
AB  - BACKGROUND: Early diagnosis of schizophrenia could improve the outcome of the
      illness. Unlike classical between-group comparisons, machine learning can
      identify subtle disease patterns on a single subject level, which could help
      realize the potential of MRI in establishing a psychiatric diagnosis. Machine
      learning has previously been predominantly tested on gray-matter structural or
      functional MRI data. In this paper we used a machine learning classifier to
      differentiate patients with a first episode of schizophrenia-spectrum disorder
      (FES) from healthy controls using diffusion tensor imaging. METHODS: We applied
      linear support-vector machine (SVM) and traditional tract based spatial
      statistics between group analyses to brain fractional anisotropy (FA) data from
      77 FES and 77 age and sex matched healthy controls. We also evaluated the effects
      of medication and symptoms on the SVM classification. RESULTS: The SVM
      distinguished between patients and controls with significant accuracy of 62.34%
      (p = 0.005). Participants with FES showed widespread FA reductions relative to
      controls in a large cluster (N  = 56,647 voxels, corrected p = 0.002). The white
      matter regions, which contributed to the correct identification of participants
      with FES, overlapped with the regions, which showed lower FA in patients relative
      to controls. There was no association between the classification performance and
      medication or symptoms. CONCLUSIONS: Our results provide a proof of concept that
      SVM might help differentiate FES patients early in the course of illness from
      healthy controls using white-matter fractional anisotropy. As there was no effect
      of medications or symptoms, the SVM classification seemed to be based on trait
      rather than state markers and appeared to capture the lower FA in FES
      participants relative to controls.

PMID- 29636017
TI  - Dissection of MAPK signaling specificity through protein engineering in a
      developmental context.
AB  - BACKGROUND: Mitogen-activated protein kinases (MAPK) signaling affects many
      processes, some of which have different outcomes in the same cell. In
      Arabidopsis, activation of a MAPK cascade consisting of YODA, MKK4/5 and MPK3/6
      inhibits early stages of stomatal developmental, but the ability to halt stomatal
      progression is lost at the later stage when guard mother cells (GMCs) transition
      to guard cells (GCs). Rather than downregulating cascade components, stomatal
      precursors must have a mechanism to prevent late stage inhibition because the
      same MKKs and MPKs mediate other physiological responses. RESULTS: We
      artificially activated the MAPK cascade using MKK7, another MKK that can modulate
      stomatal development, and found that inhibition of stomatal development is still
      possible in GMCs. This suggests that MKK4/5, but not MKK7, are specifically
      prevented from inhibiting stomatal development. To identify regions of MKKs
      responsible for cell-type specific regulation, we used a domain swap approach
      with MKK7 and a battery of in vitro and in vivo kinase assays. We found that N
      terminal regions of MKK5 and MKK7 establish specific signal-to-output connections
      like they do in other organisms, but they do so in combination with previously
      undescribed modules in the C-terminus. One of these modules encoding the GMC
      specific regulation of MKK5, when swapped with sequences from the equivalent
      region of MKK7, allows MKK5 to mediate robust inhibition of late stomatal
      development. CONCLUSIONS: Because MKK structure is conserved across species, the
      identification of new MKK specificity modules and signaling rules furthers our
      understanding of how eukaryotes create specificity in complex biological systems.

PMID- 29636019
TI  - Survival analysis of patients with invasive extramammary Paget disease:
      implications of anatomic sites.
AB  - BACKGROUND: Extramammary Paget disease (EMPD) is a rare malignant dermatosis with
      poorly defined outcomes. We investigated clinical characteristics of invasive
      EMPD at different anatomic sites and by subject demographics to determine
      prognostic factors for overall survival (OS). METHODS: All patient data were
      collected from the Surveillance, Epidemiology, and End Results (SEER) program,
      1973-2013, of the U.S. National Cancer Institute. Patients with invasive EMPD of
      skin, vulva/labia, vagina, scrotum/penis, or other sites were included. After
      excluding patients with unknown radiation status, data of 2001 patients were
      analyzed. Primary endpoint was EMPD mortality by anatomic sites. Independent
      variables included patients' demographic data, concurrent malignancy (ie, non
      EMPD related cancers), tumor size, distant metastasis, and surgery and/or
      radiation or not. RESULTS: Multivariate regression analysis showed that mortality
      was significantly higher in patients with vaginal EMPD than in patients with
      vulvar/labial EMPD (adjusted hazard ratio [aHR] = 3.26, p < 0.001). Patients with
      distant metastasis had higher mortality than those without (aHR = 3.36, p <
      0.001). Patients who received surgery had significantly lower mortality than
      those who did not receive surgery (aHR = 0.77, p = 0.030), and those treated with
      radiation had significantly higher mortality than those who did not receive
      radiation (aHR = 1.60, p = 0.002). Older age was associated with significantly
      increased mortality (aHR = 1.09, p < 0.001), and mortality was significantly
      higher in males than in females (aHR = 1.42, p = 0.008). CONCLUSIONS: In
      conclusion, among EMPD patients, mortality is higher in patients with vaginal
      EMPD than in those with vulvar/labial EMPD and higher in those who are older,
      those with concurrent malignancy or distant metastasis. Mortality is also higher
      in males than in females. Surgery is a protective factor and radiation is a risk
      factor for OS. Greater understanding of EMPD clinical characteristics, and
      considering EMPD in differential diagnosis of chronic genital and perianal
      dermatoses may provide support for early EMPD diagnosis and definitive surgical
      treatment.

PMID- 29636018
TI  - Lactobacillus paracasei feeding improves the control of secondary experimental
      meningococcal infection in flu-infected mice.
AB  - BACKGROUND: The use of probiotics to improve anti-microbial defence, such as for
      influenza infections, is increasingly recommended. However, no data are available
      on the effect of probiotics on flu-associated secondary bacterial infections.
      There is strong evidence of a spatiotemporal association between influenza virus
      infection and invasive Neisseria meningitidis. We thus investigated the effect of
      feeding mice Lactobacillus paracasei CNCM I-1518 in a mouse model of sequential
      influenza-meningococcal infection. METHODS: We intranasally infected BALB/c mice
      with a strain of influenza A virus (IAV) H3N2 that was first adapted to mice.
      Seven days later, a secondary bacterial infection was induced by intranasal
      administration of bioluminescent N. meningitidis. During the experiment, mice
      orally received either L. paracasei CNCM I-1518 or PBS as a control. The effect
      of L. paracasei administration on secondary bacterial infection by N.
      meningitidis was evaluated. RESULTS: Oral consumption of L. paracasei CNCM I-1518
      reduced the weight loss of infected mice and lowered the bioluminescent signal of
      infecting meningococci. This improvement was associated with higher recruitment
      of inflammatory myeloid cells, such as interstitial monocytes and dendritic
      cells, to the lungs. CONCLUSIONS: Our data highlight the role of the gut-lung
      axis. L. paracasei CNCM I-1518 may boost the defence against IAV infection and
      secondary bacterial infection, which should be further studied and validated in
      clinical trials.

PMID- 29636020
TI  - Sarcomatoid renal cell carcinoma: a case report and literature review.
AB  - BACKGROUND: The poorly differentiated renal cell carcinoma (RCC) with
      rhabdomyosarcomatous sarcomatoid differentiation shows a severely aggressive
      biological behavior characterized by rapid disease progression. Preoperative
      identification of the subtype with the prognostic factors and imaging features of
      sarcomatoid renal cell carcinoma (SRCC) would be of great clinical significance.
      CASE PRESENTATION: A 45-year-old male patient presented a nine day history of
      gross hematuria without any other symptoms. A computed tomography (CT) and a full
      body fluorine-18 fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) -
      computed tomography (CT) scan urogram were performed. An initial diagnosis
      identified a space-occupying lesion of the right kidney, retroperitoneal and
      right renal hulum lymph node metastases, as well as a space-occupying lesion of
      the third thoracic vertebra (T3). A right radical nephrectomy was performed.
      Pathologic analysis revealed poorly differentiated RCC with rhabdomyosarcomatous
      sarcomatoid differentiation that extends into the renal sinus and the ureteral
      (T3N1M1). Five days later, the Magnetic Resonance imaging (MRI) evidenced a
      diffused osseous metastatic disease in the thoracic and lumbar vertebra and
      multiple retroperitoneal lymph node metastases. The disease progressed quickly to
      multiple organ dysfunction syndrome (MODS) in half a month and the patient died
      of respiratory failure two days later. The patient refused any chemoradiotherapy
      in the hospital. CONCLUSIONS: Our case presents a SRCC with severe, aggressive,
      and rapid disease progression. Classifying SRCC imaging features by CT, MRI as
      well as PET-CT techniques could potentially be helpful for preoperative
      identification of the subtype. The prognostic factors of SRCC would be of great
      clinical interest.

PMID- 29636021
TI  - Perceptions, careseeking, and experiences pertaining to non-cephalic births in
      rural Sarlahi District, Nepal: a qualitative study.
AB  - BACKGROUND: In low-resource settings, a significant proportion of fetal,
      neonatal, and maternal deaths can be attributed to intrapartum-related
      complications. Certain risk factors, such as non-cephalic presentation, have a
      particularly high risk of complications. This qualitative study describes
      experiences around non-cephalic births and highlights existing perceptions and
      care-seeking behavior specific to non-cephalic presentation in rural Sarlahi
      District, Nepal. METHODS: We conducted in-depth interviews with 34 individuals,
      including women who recently gave birth to a non-cephalic infant and female
      decision-makers in their households. We also conducted two focus groups with
      mothers (have two or more children, with at least one child under age five) and
      two focus groups with grandmothers in the community. RESULTS: Several women
      described scenes of obstructed labor and practices like provision of unspecified
      injections early in labor to assist with the delivery. There were reports of
      arduous care-seeking processes from primary health centers to tertiary
      facilities, and mixed quality of care among home birth attendants and facility
      based health workers respectively. Very few women were aware of the fetal
      presentation prior to delivery, and we identified no consistent understanding
      among participants of the risks of and care strategies for non-cephalic births.
      Risk perception around non-cephalic presentation varied widely. Some participants
      were acutely aware of potential dangers, while others had not heard of non
      cephalic birth. Many interviewees said that the position in which a pregnant
      woman sleeps could impact the fetal position. Several participants had either
      taken or heard of medication intended to rotate the fetus into the correct
      position. CONCLUSIONS: Our findings suggest the mixed quality of and access to
      care associated with non-cephalic birth and a lack of consistent understanding of
      the risk of and care for non-cephalic births in rural Nepal. The high risk of the
      condition and the recommended tertiary care present a dilemma in low-resource
      settings; the logistical difficulties and the mixed quality of care make care
      seeking and referral decisions complex. While public health stakeholders strive
      to improve the quality of and access to the formal health system, those players
      must also be sensitive to the potential negative implications of promoting
      institutional care-seeking.

PMID- 29636022
TI  - Genomic heritability estimates in sweet cherry reveal non-additive genetic
      variance is relevant for industry-prioritized traits.
AB  - BACKGROUND: Sweet cherry is consumed widely across the world and provides
      substantial economic benefits in regions where it is grown. While cherry breeding
      has been conducted in the Pacific Northwest for over half a century, little is
      known about the genetic architecture of important traits. We used a genome
      enabled mixed model to predict the genetic performance of 505 individuals for 32
      phenological, disease response and fruit quality traits evaluated in the RosBREED
      sweet cherry crop data set. Genome-wide predictions were estimated using a
      repeated measures model for phenotypic data across 3 years, incorporating
      additive, dominance and epistatic variance components. Genomic relationship
      matrices were constructed with high-density SNP data and were used to estimate
      relatedness and account for incomplete replication across years. RESULTS: High
      broad-sense heritabilities of 0.83, 0.77, and 0.76 were observed for days to
      maturity, firmness, and fruit weight, respectively. Epistatic variance exceeded
      40% of the total genetic variance for maturing timing, firmness and powdery
      mildew response. Dominance variance was the largest for fruit weight and fruit
      size at 34% and 27%, respectively. Omission of non-additive sources of genetic
      variance from the genetic model resulted in inflation of narrow-sense
      heritability but minimally influenced prediction accuracy of genetic values in
      validation. Predicted genetic rankings of individuals from single-year models
      were inconsistent across years, likely due to incomplete sampling of the
      population genetic variance. CONCLUSIONS: Predicted breeding values and genetic
      values revealed many high-performing individuals for use as parents and the most
      promising selections to advance for cultivar release consideration, respectively.
      This study highlights the importance of using the appropriate genetic model for
      calculating breeding values to avoid inflation of expected parental contribution
      to genetic gain. The genomic predictions obtained will enable breeders to
      efficiently leverage the genetic potential of North American sweet cherry
      germplasm by identifying high quality individuals more rapidly than with
      phenotypic data alone.

PMID- 29636023
TI  - Mortality and treatment response amongst HIV-infected patients 50 years and older
      accessing antiretroviral services in South Africa.
AB  - BACKGROUND: Little is known about the clinical presentation and outcomes amongst
      older HIV infected populations accessing ART in sub-Saharan Africa. We compared
      mortality amongst HIV infected patients accessing ART that were <  50 years to
      those >=50 years in Kwa-Zulu Natal, South Africa. METHODS: We undertook a
      retrospective review of medical records of patients that accessed HIV services at
      the CAPRISA AIDS Treatment program (CAT) between June 2004 to December 2012 (N =
      4003). HIV infected patients, 14 years or older were enrolled. All-cause
      mortality and treatment response to ART in those < 50 years to those >=50 years
      were compared. A Kaplan-Meier curve and log-rank test were used to compare the
      cumulative probability of death between the two age groups with the primary
      endpoint being mortality. Statistical analysis was done using SAS (version 9.4.;
      SAS Institute Inc., Cary, NC, USA). RESULTS: Of 4003 individuals, 262 (6.5%) were
      >= 50 years (older group). The median age in those >=50 years and <  50 year was
      54.5 and 32.0 years, respectively. The younger group was mainly female (64.7%).
      There was no difference in mortality rate, between the older (6.9/100 person
      years (py), 95% confidence interval (CI): 4.7-9.6) and younger group (5.3/100 py,
      95% CI: 4.7-5.8) at 60 months (p = 0.137). In the multivariable model older
      patients had a significantly higher risk of death compared to younger patients.
      (hazard ratio (HR) 1.60, 95% CI: 1.08-2.39, p = 0.019).The rate of CD4+ cell
      count increase was higher in those < 50 years (beta = 0.34, 95% CI: 0.19-0.50, p
      < 0.001) with no difference in viral suppression. The older group showed
      significantly higher prevalence of diabetes (6.3%) and hypertension (21.5%), p <
      0.001. CONCLUSION: ART initiation in older HIV infected patients was associated
      with a higher mortality compared to those younger than 50 years. ART
      immunological response was less robust in older individuals. The increase in
      hypertension and diabetes among older patients suggests the need to restructure
      and integrate primary and specialized health care services into ART services.

PMID- 29636024
TI  - An ontological approach to identifying cases of chronic kidney disease from
      routine primary care data: a cross-sectional study.
AB  - BACKGROUND: Accurately identifying cases of chronic kidney disease (CKD) from
      primary care data facilitates the management of patients, and is vital for
      surveillance and research purposes. Ontologies provide a systematic and
      transparent basis for clinical case definition and can be used to identify
      clinical codes relevant to all aspects of CKD care and its diagnosis. METHODS: We
      used routinely collected primary care data from the Royal College of General
      Practitioners Research and Surveillance Centre. A domain ontology was created and
      presented in Ontology Web Language (OWL). The identification and staging of CKD
      was then carried out using two parallel approaches: (1) clinical coding
      consistent with a diagnosis of CKD; (2) laboratory-confirmed CKD, based on
      estimated glomerular filtration rate (eGFR) or the presence of proteinuria.
      RESULTS: The study cohort comprised of 1.2 million individuals aged 18 years and
      over. 78,153 (6.4%) of the population had CKD on the basis of an eGFR of < 60
      mL/min/1.73m2, and a further 7366 (0.6%) individuals were identified as having
      CKD due to proteinuria. 19,504 (1.6%) individuals without laboratory-confirmed
      CKD had a clinical code consistent with the diagnosis. In addition, a subset of
      codes allowed for 1348 (0.1%) individuals receiving renal replacement therapy to
      be identified. CONCLUSIONS: Finding cases of CKD from primary care data using an
      ontological approach may have greater sensitivity than less comprehensive
      methods, particularly for identifying those receiving renal replacement therapy
      or with CKD stages 1 or 2. However, the possibility of inaccurate coding may
      limit the specificity of this method.

PMID- 29636025
TI  - Correlates of screen time among 8-19-year-old students in China.
AB  - BACKGROUND: Previous studies have shown that prolonged time spent on screen-based
      sedentary behavior was significantly associated with lower health status in
      children, independent of physical activity levels. The study aimed to explore the
      individual and environmental correlates of screen time (ST) among 8-19-year-old
      students in China. METHODS: The study surveyed ST using a self-administered
      questionnaire in Chinese students aged 8-19 years; 1063 participants were
      included in the final analysis. Individual and environmental correlates of ST
      were assessed using a mixed-effects model (for continuous outcome variables) and
      multiple logistic regression model (for binary outcome variables). RESULTS:
      Prolonged ST was observed in 14.7% of boys and 8.9% of girls. Of the ST, weekend
      and mobile phone/tablet use represented 80% and 40%, respectively. A positive
      relationship was observed between media accessibility and ST in both boys and
      girls (p < 0.05), whereas the presence of parents/others while using screens was
      a negative factor for longer ST (p < 0.05). Among the assessed correlates, access
      to a television (TV) in students' bedrooms was associated with prolonged total
      and weekend ST (p < 0.05 and p < 0.001, respectively). However, spending time on
      a mobile phone/tablet or a computer rather than viewing a TV, along with
      increased media accessibility, increased ST. CONCLUSIONS: These results indicate
      that greater media accessibility was positively associated and the presence of
      parents/others was negatively associated with prolonged ST in both Chinese boys
      and girls. Development of new and effective strategies against prolonged ST are
      required, especially for small screen device-based ST on weekends.

PMID- 29636026
TI  - Association of IL10 and TGFB single nucleotide polymorphisms with intervertebral
      disc degeneration in Iranian population: a case control study.
AB  - BACKGROUND: Considered as one of the major causes of low back pain,
      Intervertebral disc degeneration (IVDD) is caused by several genetic and
      environmental factors. As inflammation plays an important role in disc
      degeneration, the genetic changes in both inflammatory and anti-inflammatory
      genes may play causative roles in IVDD as well. Therefore, the interactions
      between inflammatory and anti-inflammatory cytokines and also other components of
      disc matrix would determine the degree of tissue destruction in disc
      degeneration. However, there is still controversy regarding the exact role of
      inflammation and disc homeostasis imbalance in pathophysiology of IVDD.
      Therefore, current study was conducted to investigate the role of IL-10 and TGF
      beta single nucleotide polymorphisms (SNP) in Iranian IVDD patients. METHODS:
      Seventy-six IVDD patients and 140 healthy controls were enrolled in this study.
      Genomic DNA from peripheral leukocytes was tested for 3 SNPs in IL10 (L-10 
      1082G/A (rs1800896), IL-10 -819C/T (rs1800871), IL-10 -592A/C (rs1800872)) and 2
      SNPs in TGF-beta (TGF-beta Codon 10 C/T (rs1982037), and TGF-beta Codon 25 C/T
      (rs1800471) genes through PCR-SSP method. The extracted genomic DNA was genotyped
      for the aforementioned SNPs of interest using specific primers, which were coated
      in the cytokines KITs and based on the PCR-SSP method for sequencing. RESULTS:
      The 'T' allele of IL-10 -819C/T and the 'C' allele of IL-10 -592A/C were more
      prevalent among patients, whereas the 'C' and 'A' alleles of respective SNPs were
      significantly more frequent in controls. The genotypes including 'CT' of IL-10 
      819C/T, 'CA' of IL-10 -592A/C, and 'GA' of IL-10 -1082A/G were more common among
      patients, while the 'CC' genotype of both IL-10 -819C/T and IL-10 -592A/C SNPs
      were more frequent in controls. In addition, the IL-10 haplotypes including
      'ACC', 'ATA', and 'ACA' were significantly associated with disease. Meanwhile,
      the 'TC' haplotype of TGF-beta was more common among patients as well.
      CONCLUSIONS: The IL-10 SNPs were significantly associated with IVDD in Iranian
      population; which proposes that genomic alterations of anti-inflammatory
      cytokines could lead to homeostasis imbalance in intervertebral discs and
      degenerative changes.

PMID- 29636027
TI  - Contesting restrictive mobility norms among female mentors implementing a sport
      based programme for young girls in a Mumbai slum.
AB  - BACKGROUND: Harmful gender norms are known structural barriers to many public
      health and development interventions involving adolescent girls. In India,
      restrictions on girls' liberty to move freely in public spaces contribute to
      school dropout and early marriage, and negatively affect girls' health and
      wellbeing, from adolescence into adulthood. We report on mechanisms of change
      among female mentors 18 to 24 years old who contested discriminatory norms while
      implementing a sports-based programme for adolescent girls in a Mumbai slum.
      METHODS: We adopted a prospective qualitative research design. Our analysis is
      based on case studies derived from two rounds of face to face, in -depth
      interviews with 10 young women recruited to serve as mentors for the project's
      young female athletes. We combined both thematic and narrative analysis. RESULTS:
      The programme created opportunities for collective action, increasing mentors'
      ability to think and relate in a collectivized manner, and challenged the
      traditional female identity constructed for young women, which centres on
      domestic duties. The mentors themselves negotiated freedoms both in and outside
      their homes, which required careful and strategic bargaining. They changed the
      nature of key day-to-day social interactions with parents and brothers, as well
      as with neighbours, parents of their groups of athletes and men on the streets.
      They formed a new reference group for each other in terms of what was possible
      and acceptable. Demonstrating greater negotiation skills within the family helped
      win parents' trust in the mentor's ability to be safe in public spaces. Parents
      became active supporters by not giving into social sanctions of neighbours and
      relatives thus co-producing a new identity for their daughters as respectable
      young women doing 'good work'. They effectively side stepped reputational risk
      with their presence in public spaces becoming de-sexualised. CONCLUSIONS: Mentors
      contested mobility restrictions by taking risks as a group first, with collective
      agency an important step towards greater individual agency. This research
      provides important insights into addressing embedded social norms that perpetuate
      gender discriminatory practices and the social patterning of health inequalities.

PMID- 29636028
TI  - Comprehensive analysis of blood cells and plasma identifies tissue-specific
      miRNAs as potential novel circulating biomarkers in cattle.
AB  - BACKGROUND: The potential of circulating miRNAs as biomarkers of tissue function,
      both in health and disease, has been extensively demonstrated in humans. In
      addition, circulating miRNA biomarkers offer significant potential towards
      improving the productivity of livestock species, however, such potential has been
      hampered by the absence of information on the nature and source of circulating
      miRNA populations in these species. In addition, many miRNAs originally proposed
      as robust biomarkers of a particular tissue or disease in humans have been later
      shown not to be tissue specific and thus to actually have limited biomarker
      utility. In this study, we comprehensively analysed miRNA profiles in plasma and
      cell fractions of blood from cattle with the aim to identify tissue-derived
      miRNAs which may be useful as biomarkers of tissue function in this important
      food animal species. RESULTS: Using small RNA sequencing, we identified 92 miRNAs
      with significantly higher expression in plasma compared to paired blood cell
      samples (n = 4 cows). Differences in miRNA levels between plasma and cell
      fractions were validated for eight out of 10 miRNAs using RT-qPCR (n = 10 cows).
      Among miRNAs found to be enriched in plasma, we confirmed miR-122 (liver), miR
      133a (muscle) and miR-215 (intestine) to be tissue-enriched, as reported for
      other species. Profiling of additional miRNAs across different tissues identified
      the human homologue, miR-802, as highly enriched specifically in liver.
      CONCLUSIONS: These results provide novel information on the source of bovine
      circulating miRNAs and could significantly facilitate the identification of
      production-relevant tissue biomarkers in livestock. In particular, miR-802, a
      circulating miRNA not previously identified in cattle, can reportedly regulate
      insulin sensitivity and lipid metabolism, and thus could potentially provide a
      specific biomarker of liver function, a key parameter in the context of post
      partum negative energy balance in dairy cows.

PMID- 29636029
TI  - Efficacy of levetiracetam for neonatal seizures in preterm infants.
AB  - BACKGROUND: Neonatal seizures remain a significant clinical problem, and
      therapeutic options are still not diverse with limited efficacy. Levetiracetam
      (LEV) is a relatively new and wide spectrum anti-seizure medication with
      favorable pharmacokinetics and safety profile. In the recent decades, LEV has
      been increasingly used for the treatment of neonatal seizures. The aim of this
      study was to describe the experience of using LEV as the first line anti-seizure
      medication for preterm infants. METHODS: A retrospective analysis of 37 preterm
      infants who were treated with LEV as the first-line anti-seizure medication was
      performed. RESULTS: Mean gestational age of the 37 preterm infants was 31.5 +/-
      1.9 weeks (range, 26 to 36+ 6 weeks). Twenty-one infants (57%) were seizure-free
      while given LEV at the end of the first week, and no additional anti-seizure
      medication was required. Loading doses of LEV ranged from 40 to 60 mg/kg (mean 56
      mg/kg) and the maintenance dose ranged from 20 to 30 mg/kg (mean 23 mg/kg). No
      adverse effect was observed. CONCLUSIONS: Levetiracetam can be a good and safe
      choice for treatment of neonatal seizures in preterm infants. Prospective double
      blind controlled studies are needed in the future.

PMID- 29636031
TI  - Shared facial emotion processing functional network findings in medication-naive
      major depressive disorder and healthy individuals: detection by sICA.
AB  - BACKGROUND: The fundamental mechanism underlying emotional processing in major
      depressive disorder (MDD) remains unclear. To better understand the neural
      correlates of emotional processing in MDD, we investigated the role of multiple
      functional networks (FNs) during emotional stimuli processing. METHODS: Thirty
      two medication-naive subjects with MDD and 36 healthy controls (HCs) underwent an
      emotional faces fMRI task that included neutral, happy and fearful expressions.
      Spatial independent component analysis (sICA) and general linear model (GLM) were
      conducted to examine the main effect of task condition and group, and two-way
      interactions of group and task conditions. RESULTS: In sICA analysis, MDD
      patients and HCs together showed significant differences in task-related
      modulations in five FNs across task conditions. One FN mainly involving the
      ventral medial prefrontal cortex showed lower activation during fearful relative
      to happy condition. Two FNs mainly involving the bilateral inferior frontal gyrus
      and temporal cortex, showed opposing modulation relative to the ventral medial
      prefrontal cortex FN, i.e., greater activation during fearful relative to happy
      condition. Two remaining FNs involving the fronto-parietal and occipital
      cortices, showed reduced activation during both fearful and happy conditions
      relative to the neutral condition. However, MDD and HCs did not show significant
      differences in expression-related modulations in any FNs in this sample.
      CONCLUSIONS: SICA revealed differing functional activation patterns than typical
      GLM-based analyses. The sICA findings demonstrated unique FNs involved in
      processing happy and fearful facial expressions. Potential differences between
      MDD and HCs in expression-related FN modulation should be investigated further.

PMID- 29636032
TI  - Effect of Moringa oleifera consumption on diabetic rats.
AB  - BACKGROUND: Therapeutic use of leaves of M. oleifera has been evaluated in
      diabetes because of its possible capacity to decrease blood glucose and lipids
      concentration after ingestion, as result of the polyphenols content and others
      compounds. Nevertheless most results have been obtain from leaf extract,
      therefore this study would use leaf powder as the regular way of consumption of
      population to know effects over toxicity glucose, triglycerides, cholesterol,
      corporal weight, and predominant groups of microbiota. METHODS: Powdered leaf was
      administrated in different doses to know toxicity and genotoxicity using LD50 and
      micronuclei assay. Hyperglycemia was induced by alloxan on Sprague Dawley rats.
      Glucose and body weight were measured once a week meanwhile cholesterol and
      triglycerides were analyzed at the end of the study by commercial kits. Different
      organs were examined by hematoxylin-eosin technique. Lactic acid bacteria and
      Enterobacteriaceae were enumerated from stool samples. RESULTS: The tested doses
      revealed no lethal dose and no significant differences in genotoxicity parameter.
      The consumption of the leaves showed a hypoglycemic effect (< 250 mg/dL in
      diabetic M. oleifera treated group), however in corporal weight showed an
      increased (> 30 g over no M. oleifera treated groups). There was no change in
      enumeration of lactic acid bacteria (8.4 CFU/g) but there were differences in the
      predominance of type of lactobacillus and enterobacteria enumeration.
      CONCLUSIONS: These results help to increase information over the most popular use
      of M. oleifera and its safety. However there are needed more studies over the
      hypoglycemic mechanisms and effects over intestinal microbiota.

PMID- 29636033
TI  - Skepticism towards the Swedish vision zero for suicide: interviews with 12
      psychiatrists.
AB  - BACKGROUND: The main causes of suicide and how suicide could and should be
      prevented are ongoing controversies in the scientific literature as well as in
      public media. In the bill on public health from 2008 (Prop 2007/08:110), the
      Swedish Parliament adopted an overarching "Vision Zero for Suicide" (VZ) and nine
      strategies for suicide prevention. However, how the VZ should be interpreted in
      healthcare is unclear. The VZ has been criticized both from a philosophical
      perspective and against the background of clinical experience and alleged
      empirical claims regarding the consequences of regulating suicide prevention.
      This study is part of a larger research project in medical ethics with the
      overarching aim to explore whether the VZ is ethically justifiable. The aim is to
      enrich the normative discussion by investigating empirically how the VZ is
      perceived in healthcare. METHODS: Interviews based on a semi-structured interview
      guide were performed with 12 Swedish psychiatrists. The interviews were analysed
      with descriptive qualitative content analysis aiming for identifying perceptions
      of the Vision Zero for Suicide as well as arguments for and against it. RESULTS:
      Though most of the participants mentioned at least some potential benefit of the
      Vision Zero for Suicide, the overall impression was a predominant skepticism.
      Some participants focused on why they consider the VZ to be unachievable, while
      others focused more on its potential consequences and normative implications.
      CONCLUSIONS: The VZ was perceived to be impossible to realize, nonconstructive or
      potentially counterproductive, and undesirable because of potential conflicts
      with other values and interests of patients as well as the general public. There
      were also important notions of the VZ having negative consequences for the
      working conditions of psychiatrists in Sweden, in increasing their work-related
      anxiety and thwarting the patient-physician relationship.

PMID- 29636030
TI  - Pressure ulcer-related pelvic osteomyelitis: evaluation of a two-stage surgical
      strategy (debridement, negative pressure therapy and flap coverage) with
      prolonged antimicrobial therapy.
AB  - BACKGROUND: A two-stage surgical strategy (debridement-negative pressure therapy
      (NPT) and flap coverage) with prolonged antimicrobial therapy is usually proposed
      in pressure ulcer-related pelvic osteomyelitis but has not been widely evaluated.
      METHODS: Adult patients with pressure ulcer-related pelvic osteomyelitis treated
      by a two-stage surgical strategy were included in a retrospective cohort study.
      Determinants of superinfection (i.e., additional microbiological findings at
      reconstruction) and treatment failure were assessed using binary logistic
      regression and Kaplan-Meier curve analysis. RESULTS: Sixty-four pressure ulcer
      related pelvic osteomyelitis in 61 patients (age, 47 (IQR, 36-63)) were included.
      Osteomyelitis was mostly polymicrobial (73%), with a predominance of S. aureus
      (47%), Enterobacteriaceae spp. (44%) and anaerobes (44%). Flap coverage was
      performed after 7 (IQR, 5-10) weeks of NPT, with 43 (68%) positive bone samples
      among which 39 (91%) were superinfections, associated with a high ASA score (OR,
      5.8; p = 0.022). An increased prevalence of coagulase negative staphylococci (p =
      0.017) and Candida spp. (p = 0.003) was observed at time of flap coverage. An
      ESBL Enterobacteriaceae spp. was found in 5 (12%) patients, associated with
      fluoroquinolone consumption (OR, 32.4; p = 0.005). Treatment duration was as 20
      (IQR, 14-27) weeks, including 11 (IQR, 8-15) after reconstruction. After a follow
      up of 54 (IQR, 27-102) weeks, 15 (23%) failures were observed, associated with
      previous pressure ulcer (OR, 5.7; p = 0.025) and Actinomyces spp. infection (OR,
      9.5; p = 0.027). CONCLUSIONS: Pressure ulcer-related pelvic osteomyelitis is a
      difficult-to-treat clinical condition, generating an important consumption of
      broad-spectrum antibiotics. The lack of correlation between outcome and the
      debridement-to-reconstruction interval argue for a short sequence to limit the
      total duration of treatment.

PMID- 29636034
TI  - Procedural and documentation variations in intravenous infusion administration: a
      mixed methods study of policy and practice across 16 hospital trusts in England.
AB  - BACKGROUND: Procedural and documentation deviations relating to intravenous (IV)
      infusion administration can have important safety consequences. However, research
      on such deviations is limited. To address this we investigated the prevalence of
      procedural and documentation deviations in IV infusion administration and
      explored variability in policy and practice across different hospital trusts.
      METHODS: We conducted a mixed methods study. This involved observations of
      deviations from local policy including quantitative and qualitative data, and
      focus groups with clinical staff to explore the causes and contexts of
      deviations. The observations were conducted across five clinical areas (general
      medicine, general surgery, critical care, paediatrics and oncology day care) in
      16 National Health Service (NHS) trusts in England. All infusions being
      administered at the time of data collection were included. Deviation rates for
      procedural and documentation requirements were compared between trusts. Local
      data collectors and other relevant stakeholders attended focus groups at each
      trust. Policy details and reasons for deviations were discussed. RESULTS: At
      least one procedural or documentation deviation was observed in 961 of 2008 IV
      infusions (deviation rate 47.9%; 95% confidence interval 45.5-49.8%). Deviation
      rates at individual trusts ranged from 9.9 to 100% of infusions, with
      considerable variation in the prevalence of different types of deviation. Focus
      groups revealed lack of policy awareness, ambiguous policies, safety and
      practicality concerns, different organisational priorities, and wide variation in
      policies and practice relating to prescribing and administration of IV flushes
      and double-checking. CONCLUSIONS: Deviation rates and procedural and
      documentation requirements varied considerably between hospital trusts. Our
      findings reveal areas where local policy and practice do not align. Some policies
      may be impractical and lack utility. We suggest clearer evidence-based
      standardisation and local procedures that are contextually practical to address
      these issues.

PMID- 29636035
TI  - Motivational profiles, accelerometer-derived physical activity, and acute
      diabetes-related symptoms in adults with type 2 diabetes.
AB  - BACKGROUND: Using self-determination theory, the objective of this study was to
      examine, over a one-month period, how physical activity (PA) motivation would
      influence accelerometer-derived PA behavior, and ultimately, acute diabetes
      related symptoms burden among adults with type 2 diabetes (T2D adults). Using
      both a person and variable-centered approach, this objective was attained by
      means of: 1) investigating the indirect effect of PA participation on the
      relationship between PA motivation and acute diabetes-related symptom burden and
      2) examining whether participants who met PA recommendations (i.e., 150 min of
      moderate-to-vigorous PA per week) would experience less acute diabetes-related
      symptom burden over a one-month period. METHODS: A two-wave prospective
      longitudinal design was used. At time 1, participants completed a questionnaire
      assessing their PA motivation and were asked to wear an ActiGraph GT3x
      accelerometer for four consecutive weeks. At time 2, they completed a short
      questionnaire assessing their acute diabetes-related symptoms (i.e., symptoms
      related to fatigue, cognitive distress, hyperglycemia, and hypoglycemia). The
      final sample includes 165 adults (89 or 53.61% women) aged from 26 to 75 years (M
      = 62.05, SD = 8.75) with T2D, which provided at least 21 valid days of
      accelerometer-derived data. RESULTS: First, results of a path analysis
      demonstrated that over a one-month period, the average number of minutes spent
      practicing moderate to vigorous PA per week mediated the relationship between
      intrinsic and external PA motivation and the level of burden associated with the
      following diabetes-related symptoms: fatigue, cognitive distress, and
      hyperglycemia. In addition, results of covariance analyses showed that
      participants meeting PA recommendations also reported significantly less burden
      associated with these three symptoms over a month period. Then, the existence of
      four motivational profiles (Self-Determined, High Introjected, Low Motivation,
      and Non-Self-Determined) was confirmed using a k-means analysis. Results of
      covariance and chi-square analyses further showed, respectively, that compared to
      other motivational profiles, the Self-Determined profile was associated with a
      higher score on weekly PA participation and meeting PA recommendations.
      CONCLUSIONS: The results highlight the importance of promoting autonomous motives
      for PA participation among T2D adults. They also suggest that T2D adults meeting
      PA recommendations experience less acute diabetes-related symptoms burden, which
      further support the importance of their PA motivation.

PMID- 29636037
TI  - Correction to: Development and application of an indirect enzyme-linked
      immunosorbent assay based on recombinant capsid protein for the detection of mink
      circovirus infection.
AB  - The original article [1] contained an error whereby Fig. 2 had processed
      incorrectly. The correct version of Fig. 2 is now displayed in the original
      article as well as ahead.

PMID- 29636036
TI  - Leaving the emergency department without complete care: disparities in American
      Indian children.
AB  - BACKGROUND: Children who leave the emergency department (ED) without complete
      evaluation or care (LWCET) have poorer outcomes in general. Previous studies have
      found that American Indian (AI) children have higher rates of LWCET than other
      racial or ethnic groups. Therefore, this study aims to examine LWCET in AI
      children by exploring differences by ED location and utilization patterns.
      METHODS: This is a retrospective cohort study of five EDs in the upper Midwest
      between June 2011 and May 2012. We included all visits by children aged 0-17 who
      identified as African American (AA), AI or White. Logistic regression was used to
      determine differences in LWCET by race and ED location controlling for other
      possible confounding factors including sex, age, insurance type, triage level,
      distance from ED, timing of visit, and ED activity level. RESULTS: LWCET occurred
      in 1.73% of 68,461 visits made by 47,228 children. The multivariate model
      revealed that AIs were more likely to LWCET compared to White children (Odds
      Ratio (OR) = 1.62, 95% Confidence Interval (CI) = 1.30-2.03). There was no
      significant difference in LWCET between AA and White children. Other factors
      significantly associated with LWCET included triage level, distance from the ED,
      timing of visit, and ED activity level. CONCLUSION: Our results show that AI
      children have higher rates of LWCET compared to White children; this association
      is different from other racial minority groups. There are likely complex factors
      affecting LWCET in AI children throughout the upper Midwest, which necessitates
      further exploration.

PMID- 29636038
TI  - Severity and susceptibility: measuring the perceived effectiveness and
      believability of tobacco health warnings.
AB  - BACKGROUND: Pictorial tobacco health warning labels (HWLs) have been shown to be
      more effective than text-only HWLs in changing smoking attitudes and intentions.
      However, there is contradictory evidence regarding how the severity of the
      content of HWLs influences responses to them. METHODS: We examined the perceived
      believability and effectiveness of HWLs in an online study using a convenience
      sample of non-smokers (N = 437) and smokers (N = 436). HWLs were in one of three
      presentation formats: (text-only, a moderately severe image or highly severe
      image) and focussed on three disease outcomes (lung cancer, blindness or tooth
      and gum disease). Participants rated the effectiveness and believability of each
      HWL and also rated their perceived susceptibility to each disease. RESULTS: A 2
      (smoking status) * 3 (presentation format) * 3 (disease outcome) ANOVA was run
      for both believability and effectiveness ratings. The most severe pictorial HWLs
      received the highest believability and effectiveness ratings and as expected, the
      text-only HWLs received the lowest. Lung cancer HWLs were rated most believable
      and effective, with the blindness HWLs receiving the lowest scores. A 2 (smoking
      status) * 3 (disease outcome) ANOVA was conducted on the ratings of perceived
      susceptibility to the three diseases. Smokers considered themselves to be more
      susceptible to all three diseases, and among smokers, perceived susceptibility to
      the diseases was positively correlated with effectiveness and believability
      ratings of the HWLs. CONCLUSION: Our findings support previous evidence that
      pictorial HWLs are rated as more effective and believable than text-only
      warnings, and provide some support for the use of severe or 'grotesque' HWLs on
      tobacco products. Our data also suggest that HWLs should aim to increase
      perceived susceptibility to disease, as this was positively related to perceived
      message effectiveness and believability.

PMID- 29636039
TI  - Meta-analysis on the effectiveness of team-based learning on medical education in
      China.
AB  - BACKGROUND: Team-based learning (TBL) has been adopted as a new medical
      pedagogical approach in China. However, there are no studies or reviews
      summarizing the effectiveness of TBL on medical education. This study aims to
      obtain an overall estimation of the effectiveness of TBL on outcomes of
      theoretical teaching of medical education in China. METHODS: We retrieved the
      studies from inception through December, 2015. Chinese National Knowledge
      Infrastructure, Chinese Biomedical Literature Database, Chinese Wanfang Database,
      Chinese Scientific Journal Database, PubMed, EMBASE and Cochrane Database were
      searched. The quality of included studies was assessed by the Newcastle-Ottawa
      scale. Standardized mean difference (SMD) was applied for the estimation of the
      pooled effects. Heterogeneity assumption was detected by I2 statistics, and was
      further explored by meta-regression analysis. RESULTS: A total of 13 articles
      including 1545 participants eventually entered into the meta-analysis. The
      quality scores of these studies ranged from 6 to 10. Altogether, TBL
      significantly increased students' theoretical examination scores when compared
      with lecture-based learning (LBL) (SMD = 2.46, 95% CI: 1.53-3.40). Additionally,
      TBL significantly increased students' learning attitude (SMD = 3.23, 95% CI: 2.27
      4.20), and learning skill (SMD = 2.70, 95% CI: 1.33-4.07). The meta-regression
      results showed that randomization, education classification and gender diversity
      were the factors that caused heterogeneity. CONCLUSIONS: TBL in theoretical
      teaching of medical education seems to be more effective than LBL in improving
      the knowledge, attitude and skill of students in China, providing evidence for
      the implement of TBL in medical education in China. The medical schools should
      implement TBL with the consideration on the practical teaching situations such as
      students' education level.

PMID- 29636040
TI  - Telemedical monitoring of patients with chronic heart failure has a positive
      effect on total health costs.
AB  - BACKGROUND: Telemedical programs for patients with chronic heart failure have
      shown inconsistent effects on survival and hospitalization. Few studies analyzed
      effects of telemedical interventions on health costs, although this outcome may
      determine whether or not a successful program will be adopted by health insurance
      providers. We evaluated a large sized telemedicine program provided by a German
      statutory health insurance, consisting of regular telephone contacts and, for a
      subgroup of the participants, provision of an electronic scale in a routine care
      setting. We examined the effects of the program on the total healthcare costs
      after one year compared to a matched control group. METHODS: The evaluation was
      based on reimbursement data of the statutory health insurance. Participants of
      the program were matched to appropriate controls using a combination of exact
      (e.g. 5-year age group, gender, NYHA class) and propensity score (e.g.
      medication, psychiatric comorbidity) matching. The total health costs after one
      year were calculated on the basis of regression analyses in an intention-to-treat
      approach. In a sensitivity analysis, the subgroup of patients with a documented
      beginning of the intervention was examined. RESULTS: Two thousand six hundred
      twenty two patients with chronic heart failure (55% male, mean age: 73.7 years)
      were included in the intervention program. 1943 participants (74%) could be
      matched with appropriate control patients. The telemedicine monitoring program
      for patients with chronic heart failure reduced total health costs after 12
      months of the intervention: - 276? per quarter year in rural regions and - 18? in
      urban regions compared to the control group. CONCLUSIONS: The telemedicine
      program could reduce total health costs, especially in rural regions in Germany.

PMID- 29636041
TI  - Voices from the frontline: barriers and strategies to improve tuberculosis
      infection control in primary health care facilities in South Africa.
AB  - BACKGROUND: Tuberculosis (TB) infection control at primary healthcare (PHC) level
      remains problematic, especially in South Africa. Improvements are significantly
      dependent on healthcare workers' (HCWs) behaviours, underwriting an urgent need
      for behaviour change. This study sought to 1) identify factors influencing TB
      infection control behaviour at PHC level within a high TB burden district and 2)
      in a participatory manner elicit recommendations from HCWs for improved TB
      infection control. METHOD: A qualitative case study was employed. TB nurses and
      facility managers in the Mangaung Metropolitan District, South Africa,
      participated in five focus group and nominal group discussions. Data was
      thematically analysed. RESULTS: Utilising the Information Motivation and
      Behaviour (IMB) Model, major barriers to TB infection control information
      included poor training and conflicting policy guidelines. Low levels of
      motivation were observed among participants, linked to feelings of powerlessness,
      negative attitudes of HCWs, poor district health support, and general health
      system challenges. With a few exceptions, most behaviours necessary to achieve TB
      risk-reduction, were generally regarded as easy to accomplish. CONCLUSIONS:
      Strategies for improved TB infection control included: training for comprehensive
      TB infection control for all HCWs; clarity on TB infection control policy
      guidelines; improved patient education and awareness of TB infection control
      measures; emphasis on the active role HCWs can play in infection control as
      change agents; improved social support; practical, hands-on training or role
      playing to improve behavioural skills; and the destigmatisation of TB/HIV among
      HCWs and patients.

PMID- 29636042
TI  - Gender differences in the evaluation of care for patients with type 2 diabetes: a
      cross-sectional study (ZODIAC-52).
AB  - BACKGROUND: Little is known about the association between patient-related factors
      and patients' evaluation of care. Aim was to investigate which patient-related
      factors are associated with patients' evaluation of care in men and women with
      type 2 diabetes (T2D) in primary care. METHODS: This cross-sectional study
      included 1102 patients with T2D from 52 general practices. We measured patients'
      evaluation with the EUROPEP questionnaire and collected demographic, clinical and
      psychological data from questionnaires and health records. Stepwise linear
      regression analyses were used. RESULTS: The location where the questionnaire was
      completed (at home or at the general practice) was associated with all outcomes
      in men and women. Next to this, in men, explanatory factors for the care provider
      EUROPEP subscale were use of insulin, having some problems with T2D self-care and
      coffee consumption (R2 8.4%); coffee consumption was associated with the general
      practice subscale (R2 4.0%). In women, well-being, quality of life, following a
      general diet, and use of oral glucose-lowering drugs were associated with the
      care provider subscale (R2 16.8%). For the general practice subscale, well-being
      and age were explanatory factors (R2 9.4%). CONCLUSIONS: Only a few factors were
      found to be associated with patients' evaluation of care for men and women with
      T2D. Taken together, these factors explained only a small part of the variance of
      the EUROPEP scores. This explained variance was largely attributable to the
      location where the questionnaire was completed. We therefore advise to be aware
      of the possible consequences of filing-out questionnaires about patients'
      evaluation of care at the general practice. TRIAL REGISTRATION: NCT01570140
      (Clinicaltrials.gov). Registered 29 March 2012.

PMID- 29636043
TI  - Experiences of young smokers in quitting smoking in twin cities of Pakistan: a
      phenomenological study.
AB  - BACKGROUND: Smoking is highly prevalent in Pakistan claiming the lives of over
      100,000 individuals every year. A significant proportion of smokers (24.7%) make
      an attempt to quit each year but 97.4% fail to quit successfully. Little is known
      about the reasons for, and experiences of, failed quit attempts. This study was
      carried out to explore the experiences of young male smokers in quitting smoking
      in the twin cities of Pakistan METHOD: A qualitative study was carried out using
      a phenomenological approach in Rawalpindi and Islamabad. A total of 11
      participants were interviewed. All study participants were male and had made at
      least one quit attempt. Study participants were a mix of smokers who failed to
      quit smoking, intermittent smokers and successful quitters. Streubert's (1991)
      method of phenomenology was followed during data analysis. RESULTS: The
      experiences of smokers while smoking "the smoking phase" have major effects on
      their journey towards quitting smoking. The smoking phase consists of three major
      stages: contact with initial smoking stimuli, the journey from first puff to
      enjoying smoking and then finally smoking becoming part of life. However, the
      journey towards quitting smoking is not as simple as the journey towards becoming
      a smoker. Instead, smokers get trapped in three overlapping cycles of smoking and
      quit attempts: smoking & forced quitting, smoking & intentional quitting, and
      smoking & intermittent smoking before successful quitting. Breaking the cycle is
      not easy in the presence of trapping factors (addiction, high availability, easy
      affordability, conducive social setup and low perceived risks of smoking). Three
      factors play a major role in breaking these cycles which are strong will power,
      continuous peer support and avoidance of smokers' company. CONCLUSION: A young
      smoker, during his experience of quitting smoking gets entrapped in several
      overlapping cycles of smoking & quit attempts before successful quitting. There
      are known entrapping factors as well as factors which help in breaking these
      cycles. Targeted interventions are needed to facilitate smoking cessation among
      young smokers in Pakistan.

PMID- 29636044
TI  - Serum and salivary ferritin and Hepcidin levels in patients with chronic
      periodontitis and type 2 diabetes mellitus.
AB  - BACKGROUND: Iron disorder and abnormal expression of hepcidin play important
      roles in many diseases, but it is still unclear in chronic periodontitis (CP) and
      type 2 diabetes mellitus (T2DM). We aimed to assess ferritin and hepcidin levels
      in serum and saliva of CP patients with or without T2DM. METHODS: Serum and
      unstimulated whole saliva samples were collected from 88 participants, who were
      categorized into 4 groups based on the presence or absence of CP or T2DM.
      Demographics and general health parameters were recorded. Full-mouth clinical
      periodontal parameters including probing pocket depth, clinical attachment loss,
      bleeding index, and plaque index were recorded. Chemiluminescence microparticle
      immunoassay and enzyme-linked immunosorbent assay were used to detect ferritin
      and hepcidin concentrations, respectively, in serum and saliva. RESULTS: Serum
      ferritin and hepcidin levels in the CP and CP with T2DM groups were higher than
      in the control group (P < 0.05). Serum hepcidin and serum ferritin are linear
      correlated (P < 0.001). Serum hepcidin/ferritin values in the CP with T2DM group
      were significantly lower than those in the T2DM and control groups. Moreover,
      salivary ferritin levels in the CP and T2DM groups were higher than those in the
      control group (P < 0.05). There was positively correlation between salivary
      ferritin and serum ferritin (P = 0.017). Hepcidin concentrations were relatively
      low in saliva. CONCLUSIONS: These results suggest that iron overload and hepcidin
      inadequacy existed in CP with T2DM patients. Salivary ferritin might provide a
      reference for body iron load. TRIAL REGISTRATION: ChiCTR-ROC-17012780.

PMID- 29636045
TI  - Sarcopenic obesity assessed using dual energy X-ray absorptiometry (DXA) can
      predict cardiovascular disease in patients with type 2 diabetes: a retrospective
      observational study.
AB  - BACKGROUND: Sarcopenic obesity, defined as reduced skeletal muscle mass and power
      with increased adiposity, was reported to be associated with cardiovascular
      disease risks in previous cross-sectional studies. Whole body dual-energy X-ray
      absorptiometry (DXA) can simultaneously evaluate both fat and muscle mass,
      therefore, whole body DXA may be suitable for the diagnosis of sarcopenic
      obesity. However, little is known regarding whether sarcopenic obesity determined
      using whole body DXA could predict incident cardiovascular disease (CVD). The aim
      of this study was to investigate the impact of sarcopenic obesity on incident CVD
      in patients with type 2 diabetes. METHODS: A total of 716 Japanese patients (mean
      age 65 +/- 13 years; 47.0% female) were enrolled. Android fat mass (kg), gynoid
      fat mass (kg), and skeletal muscle index (SMI) calculated as appendicular non-fat
      mass (kg) divided by height squared (m2), were measured using whole body DXA.
      Sarcopenic obesity was defined as the coexistence of low SMI and obesity
      determined by four patterns of obesity as follows: android to gynoid ratio (A/G
      ratio), android fat mass or percentage of body fat (%BF) was higher than the sex
      specific median, or body mass index (BMI) was equal to or greater than 25 kg/m2.
      The study endpoint was the first occurrence or recurrence of CVD. RESULTS: Over a
      median follow up of 2.6 years (IQR 2.1-3.2 years), 53 patients reached the
      endpoint. Sarcopenic obesity was significantly associated with incident CVD even
      after adjustment for the confounding variables, when using A/G ratio [hazard
      ratio (HR) 2.63, 95% CI 1.10-6.28, p = 0.030] and android fat mass (HR 2.57, 95%
      CI 1.01-6.54, p = 0.048) to define obesity, but not %BF (HR 1.67, 95% CI 0.69
      4.02, p = 0.252), and BMI (HR 1.55, 95% CI 0.44-5.49, p = 0.496). CONCLUSIONS:
      The present data suggest that the whole body DXA is valuable in the diagnosis of
      sarcopenic obesity (high A/G ratio or android fat mass with low SMI) to determine
      the risk of CVD events in patients with type 2 diabetes. Meanwhile, sarcopenic
      obesity classified with low SMI, and high %BF or BMI was not associated with
      incident CVD.

PMID- 29636046
TI  - Health economic evaluations based on routine data in Germany: a systematic
      review.
AB  - BACKGROUND: Improved data access and funding for health services research have
      promoted the application of routine data to measure costs and effects of
      interventions within the German health care system. Following the trend towards
      real world evidence, this review aims to evaluate the status and quality of
      health economic evaluations based on routine data in Germany. METHODS: To
      identify relevant economic evaluations, a systematic literature search in the
      databases PubMed and EMBASE was complemented by a manual search. The included
      studies had to be full economic evaluations using German routine data to measure
      either costs, effects, or both. Study characteristics were assessed with a
      structured template. Additionally, the Consolidated Health Economic Evaluation
      Reporting Standards (CHEERS) were used to measure quality of reporting. RESULTS:
      In total, 912 records were identified and 35 studies were included in the further
      analysis. The majority of these studies was published in the past 5 years (n =
      27, 77.1%) and used insurance claims data as a source of routine data (n = 30,
      85.7%). The most common method used for handling selection bias was propensity
      score matching. With regard to the reporting quality, 42.9% (n = 15) of the
      studies satisfied at least 80% of the criteria on the CHEERS checklist.
      CONCLUSIONS: This review confirms that routine data has become an increasingly
      common data source for health economic evaluations in Germany. While most studies
      addressed the application of routine data, this analysis reveals deficits in
      considering methodological particularities and in reporting quality of economic
      evaluations based on routine data. Nevertheless, this review demonstrates the
      overall potential of routine data for economic evaluations.

PMID- 29636047
TI  - Liraglutide suppresses non-esterified free fatty acids and soluble vascular cell
      adhesion molecule-1 compared with metformin in patients with recent-onset type 2
      diabetes.
AB  - BACKGROUND: It has been suggested that liraglutide could have an impact on
      glucose and lipid metabolism disorder and adhesion molecule activation, which may
      play important roles in the vascular damage of diabetes. In this study, we
      examined the effects of liraglutide versus metformin on non-esterified free fatty
      acids, beta-cell insulin secretion, and adhesion molecule levels in patients with
      recent-onset type 2 diabetes mellitus. METHODS: In this study, 60 patients newly
      diagnosed with type 2 diabetes mellitus (mean age 33.97 +/- 5.67 years) were
      randomly assigned to receive once-daily subcutaneous liraglutide or oral
      metformin. Before the study and after the 8-week treatment period, a 75 g oral
      glucose tolerance test was performed. Plasma glucose, lipids and lipoprotein,
      plasma insulin, glycaemic and insulin responses, non-esterified free fatty acids
      (NEFA), and soluble vascular cell adhesion molecule-1 (sVCAM-1) levels were
      evaluated. RESULTS: After 8 weeks, 120 min of NEFA (155 +/- 125 vs 99 +/- 73
      umol/L, P = 0.026) and the levels of sVCAM-1 (465 +/- 136 vs 382 +/- 131 ng/ml, P
      = 0.013) significantly decreased, while the early phase insulin secretion index
      (24.94 [7.78, 38.89] vs. 31.13 [17.67, 59.09], P = 0.031), fasting plasma insulin
      (104 [51, 123] vs 113 [54, 171] mIU/L, P = 0.015), 60 min plasma insulin (326
      [165, 441] vs 471 [334, 717] mIU/L, P = 0.005), 120 min plasma insulin (401 [193,
      560] vs 500 [367, 960] mIU/L, P = 0.047), and insulin area under the curve
      (AUCins) (648 [321, 742] vs 738 [451, 1118] mIU/L, P = 0.005) remarkably
      increased for patients in the liraglutide treatment group. The levels of sVCAM-1
      dramatically decreased after 8 weeks of liraglutide treatment (503 +/- 182 vs 382
      +/- 131 ng/ml, P = 0.046) compared to that of the metformin treatment group. At
      the same time, the differences before and after liraglutide treatment in 120 min
      of NEFA (- 32 [- 96, - 5] vs 5 [- 35, 38] umol/L, P = 0.033) and AUCins (738
      [451, 1118] vs 594 [357, 1216] mIU/L, P = 0.014) were remarkably enhanced
      compared to that of the metformin therapy. Nevertheless, there were no
      significant differences in fasting NEFA after liraglutide or metformin treatment.
      The reduction of 120 min NEFA (DeltaNEFA) was positively correlated with the
      decrease of sVCAM-1 (DeltasVCAM-1) after 8 weeks of liraglutide treatment (r =
      0.523, P = 0.003). CONCLUSIONS: Our results demonstrate that liraglutide
      administration is more effective than metformin in reducing 120 min NEFA and
      suppressing sVCAM-1 levels for recent-onset type 2 diabetes mellitus. We suggest
      that this outcome may be because liraglutide is associated with potentiating
      insulin secretion capacity, inhibiting vascular inflammatory cytokines, and
      antagonizing atherosclerosis.

PMID- 29636048
TI  - Surgical management of urolithiasis - a systematic analysis of available
      guidelines.
AB  - BACKGROUND: Several societies around the world issue guidelines incorporating the
      latest evidence. However, even the most commonly cited guidelines of the European
      Association of Urology (EAU) and the American Urological Association (AUA) leave
      the clinician with several treatment options and differ on specific points. We
      aimed to identify discrepancies and areas of consensus between guidelines to give
      novel insights into areas where low consensus between the guideline panels
      exists, and therefore where more evidence might increase consensus. METHODS: The
      webpages of the 61 members of the Societe Internationale d'Urologie were analysed
      to identify all listed or linked guidelines. Decision trees for the surgical
      management of urolithiasis were derived, and a comparative analysis was performed
      to determine consensus and discrepancies. RESULTS: Five national and one
      international guideline (EAU) on surgical stone treatment were available for
      analysis. While 7 national urological societies refer to the AUA guidelines and
      11 to the EAU guidelines, 43 neither publish their own guidelines nor refer to
      others. Comparative analysis revealed a high degree of consensus for most renal
      and ureteral stone scenarios. Nevertheless, we also identified a variety of
      discrepancies between the different guidelines, the largest being the approach to
      the treatment of proximal ureteral calculi and larger renal calculi. CONCLUSIONS:
      Six guidelines with recommendations for the surgical treatment of urolithiasis to
      support urologists in decision-making were available for inclusion in our
      analysis. While there is a high grade of consensus for most stone scenarios, we
      also detected some discrepancies between different guidelines. These are,
      however, controversial situations where adequate evidence to assist with decision
      making has yet to be elicited by further research.

PMID- 29636049
TI  - Associations of the plasma lipidome with mortality in the acute respiratory
      distress syndrome: a longitudinal cohort study.
AB  - BACKGROUND: It is unknown if the plasma lipidome is a useful tool for improving
      our understanding of the acute respiratory distress syndrome (ARDS). Therefore,
      we measured the plasma lipidome of individuals with ARDS at two time-points to
      determine if changes in the plasma lipidome distinguished survivors from non
      survivors. We hypothesized that both the absolute concentration and change in
      concentration over time of plasma lipids are associated with 28-day mortality in
      this population. METHODS: Samples for this longitudinal observational cohort
      study were collected at multiple tertiary-care academic medical centers as part
      of a previous multicenter clinical trial. A mass spectrometry shot-gun lipidomic
      assay was used to quantify the lipidome in plasma samples from 30 individuals.
      Samples from two different days were analyzed for each subject. After removing
      lipids with a coefficient of variation > 30%, differences between cohorts were
      identified using repeated measures analysis of variance. The false discovery rate
      was used to adjust for multiple comparisons. Relationships between significant
      compounds were explored using hierarchical clustering of the Pearson correlation
      coefficients and the magnitude of these relationships was described using
      receiver operating characteristic curves. RESULTS: The mass spectrometry assay
      reliably measured 359 lipids. After adjusting for multiple comparisons, 90
      compounds differed between survivors and non-survivors. Survivors had higher
      levels for each of these lipids except for five membrane lipids. Glycerolipids,
      particularly those containing polyunsaturated fatty acid side-chains, represented
      many of the lipids with higher concentrations in survivors. The change in lipid
      concentration over time did not differ between survivors and non-survivors.
      CONCLUSIONS: The concentration of multiple plasma lipids is associated with
      mortality in this group of critically ill patients with ARDS. Absolute lipid
      levels provided more information than the change in concentration over time.
      These findings support future research aimed at integrating lipidomics into
      critical care medicine.

PMID- 29636050
TI  - Pectoralis muscle area and mortality in smokers without airflow obstruction.
AB  - BACKGROUND: Low muscle mass is associated with increased mortality in the general
      population but its prognostic value in at-risk smokers, those without expiratory
      airflow obstruction, is unknown. We aimed to test the hypothesis that reduced
      muscle mass is associated with increased mortality in at-risk smokers. METHODS:
      Measures of both pectoralis and paravertebral erector spinae muscle cross
      sectional area (PMA and PVMA, respectively) as well as emphysema on chest
      computed tomography (CT) scans were performed in 3705 current and former at-risk
      smokers (>=10 pack-years) aged 45-80 years enrolled into the COPDGene Study
      between 2008 and 2013. Vital status was ascertained through death certificate.
      The association between low muscle mass and mortality was assessed using Cox
      regression analysis. RESULTS: During a median of 6.5 years of follow-up, 212
      (5.7%) at-risk smokers died. At-risk smokers in the lowest (vs. highest) sex
      specific quartile of PMA but not PVMA had 84% higher risk of death in adjusted
      models for demographics, smoking, dyspnea, comorbidities, exercise capacity, lung
      function, emphysema on CT, and coronary artery calcium content (hazard ratio [HR]
      1.85 95% Confidence interval [1.14-3.00] P = 0.01). Results were consistent when
      the PMA index (PMA/height2) was used instead of quartiles. The association
      between PMA and death was modified by smoking status (P = 0.04). Current smokers
      had a significantly increased risk of death (lowest vs. highest PMA quartile, HR
      2.25 [1.25-4.03] P = 0.007) while former smokers did not. CONCLUSIONS: Low muscle
      mass as measured on chest CT scans is associated with increased mortality in
      current smokers without airflow obstruction. TRIAL REGISTRATION: NCT00608764.

PMID- 29636051
TI  - Scaling up malaria intervention "packages" in Senegal: using cost effectiveness
      data for improving allocative efficiency and programmatic decision-making.
AB  - BACKGROUND: Senegal's National Malaria Control Programme (NMCP) implements
      control interventions in the form of targeted packages: (1) scale-up for impact
      (SUFI), which includes bed nets, intermittent preventive treatment in pregnancy,
      rapid diagnostic tests, and artemisinin combination therapy; (2) SUFI + reactive
      case investigation (focal test and treat); (3) SUFI + indoor residual spraying
      (IRS); (4) SUFI + seasonal malaria chemoprophylaxis (SMC); and, (5) SUFI + SMC +
      IRS. This study estimates the cost effectiveness of each of these packages to
      provide the NMCP with data for improving allocative efficiency and programmatic
      decision-making. METHODS: This study is a retrospective analysis for the period
      2013-2014 covering all 76 Senegal districts. The yearly implementation cost for
      each intervention was estimated and the information was aggregated into a package
      cost for all covered districts. The change in the burden of malaria associated
      with each package was estimated using the number of disability adjusted life
      years (DALYs) averted. The cost effectiveness (cost per DALY averted) was then
      calculated for each package. RESULTS: The cost per DALY averted ranged from $76
      to $1591 across packages. Using World Health Organization standards, 4 of the 5
      packages were "very cost effective" (less than Senegal's GDP per capita).
      Relative to the 2 other packages implemented in malaria control districts, the
      SUFI + SMC package was the most cost-effective package at $76 per DALY averted.
      SMC seems to make IRS more cost effective: $582 per DALY averted for SUFI + IRS
      compared with $272 for the SUFI + IRS + SMC package. The SUFI + focal test and
      treat, implemented in malaria elimination districts, had a cost per DALY averted
      of $1591 and was only "cost-effective" (less than three times Senegal's per
      capita GDP). CONCLUSION: Senegal's choice of deploying malaria interventions by
      packages seems to be effectively targeting high burden areas with a wide range of
      interventions. However, not all districts showed the same level of performance,
      indicating that efficiency gains are still possible.

PMID- 29636052
TI  - Experiences of primary care physicians and staff following lean workflow
      redesign.
AB  - BACKGROUND: In response to growing pressures on primary care, leaders have
      introduced a wide range of workforce and practice innovations, including team
      redesigns that delegate some physician tasks to nonphysicians. One important
      question is how such innovations affect care team members, particularly in view
      of growing dissatisfaction and burnout among healthcare professionals. We examine
      the work experiences of primary care physicians and staff after implementing Lean
      based workflow redesigns. This included co-locating physician and medical
      assistant dyads, delegating significant responsibilities to nonphysician staff,
      and mandating greater coordination and communication among all care team members.
      METHODS: The redesigns were implemented and scaled in three phases across 46
      primary care departments in a large ambulatory care delivery system. We fielded
      1164 baseline and 1333 follow-up surveys to physicians and other nonphysician
      staff (average 73% response rate) to assess workforce engagement (e.g., job
      satisfaction, motivation), perceptions of the work environment, and job-related
      burnout. We conducted multivariate regressions to detect changes in experiences
      after the redesign, adjusting for respondent characteristics and clustering of
      within-clinic responses. RESULTS: We found that both physicians and nonphysician
      staff reported higher levels of engagement and teamwork after implementing
      redesigns. However, they also experienced higher levels of burnout and
      perceptions of the workplace as stressful. Trends were the same for both
      occupational groups, but the increased reports of stress were greater among
      physicians. Additionally, members of all clinics, except for the pilot site that
      developed the new workflows, reported higher burnout, while perceptions of
      workplace stress increased in all clinics after the redesign. CONCLUSIONS: Our
      findings partially align with expectations of work redesign as a route to
      improving physician and staff experiences in delivering care. Although teamwork
      and engagement increased, the redesigns in our study were not enough to moderate
      long-standing challenges facing primary care. Yet higher levels of empowerment
      and engagement, as observed in the pilot clinic, may be particularly effective in
      facilitating improvements while combating fatigue. To help practices cope with
      increasing burdens, interventions must directly benefit healthcare professionals
      without overtaxing an already overstretched workforce.

PMID- 29636053
TI  - What should we expect from Switzerland's compulsory dental insurance reform?
AB  - BACKGROUND: A vast and heated debate is arising in Switzerland as a result of
      some recent citizens' initiatives aimed at introducing compulsory dental health
      care insurance. The Grand Conseils of the Vaud, Geneva, and Neuchatel cantons
      recently approved three public initiatives and their citizens are expected to
      vote on the proposal in 2018. The process of collecting signatures has begun in
      several other cantons and the discussion has now moved to a national level.
      DISCUSSION: At present, there is no scientific research that can help policy
      makers and citizens to understand the main economic implications of such reform.
      We attempt to fill this gap by analysing three critical issues: the level and
      determinants of unmet needs for dental care in Switzerland; the protection of
      vulnerable individuals; and the economic sustainability of reform. RESULTS AND
      SHORT CONCLUSIONS: The results show that income is not a unique determinant of
      barriers to access to dental care but rather, cultural and socio-demographic
      factors impact the perceived level of unmet dental care needs. The reform might
      only partially, if at all, improve the equity of the current system. In addition,
      the results show that the 1% wage-based contribution that the reform promoters
      suggest should finance the insurance is inadequate to provide full and free
      dental care to Swiss residents, but is merely sufficient to guarantee basic
      preventive care, whereas this could be provided by dental hygienists for less.

PMID- 29636055
TI  - Evaluation of the antioxidant and endothelial protective effects of Lysimachia
      christinae Hance (Jin Qian Cao) extract fractions.
AB  - BACKGROUND: Lysimachia christinae Hance is a traditional Chinese medicine with
      diuretic, detumescent, and detoxifying effects. Our aimed to optimize the
      extraction protocol to maximize the yield of flavonoids from Lysimachia
      christinae Hance, and evaluate the pharmacological activities of four fractions,
      namely, petroleum ether (PE), ethyl acetate (EA), n-butanol (NB), and aqueous
      (AQ) fractions, of the ethanolic extract of Lysimachia christinae Hance. METHODS:
      The flavonoid monomers in the crude extract were characterized via high
      performance liquid chromatography (HPLC), were used as markers for extract
      quality control and standardization. The total flavonoid, total phenolic, and
      total polysaccharide contents of each fraction were determined by
      spectrophotometry. Further, the in vitro free radical (diphenylpicrylhydrazyl,
      2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid), superoxide, and hydroxyl
      radicals) scavenging activities, and antioxidant capacity in endothelial cells
      were evaluated for each fraction. RESULTS: After optimizing the extraction
      protocol to maximize the total flavonoid yield from L. christinae Hance, the NB
      fractions had the highest total flavonoid (39.4 +/- 4.55 mg RE/g), total phenolic
      (41.1 +/- 3.07 mg GAE/g) and total polysaccharide (168.1 +/- 7.07 mg GE/g); In
      addition, the NB fraction of the ethanolic extract of L. christinae Hance reveal
      the strongest radical-scavenging activity, antioxidant activity and protective
      effects against H2O2-induced injury in HUVECs. CONCLUSIONS: Among the four
      fractions of L. christinae Hance, the NB fraction showed the most potent
      antioxidant and endothelial protective effects, which may be attributed to its
      high flavonoid, phenolic contents and optimal portfolio of different active
      ingredients of NB fractions of the ethanolic extract of L. christinae Hance. This
      study might improve our understanding of the pharmacological activities of L.
      christinae Hance, thereby facilitating its use in disease prevention and
      treatment.

PMID- 29636054
TI  - Policy implications of regional variations in eye disease detection and treatment
      on Prince Edward Island: a repeated cross-sectional analysis, 2010-2012.
AB  - BACKGROUND: In Canada, government insurance covers eye care services provided by
      ophthalmologists and other physicians. However, government coverage for services
      provided by optometrists, non-medical school trained primary eye care providers,
      varies regionally. Little is known about the impact of a funding model in which
      ophthalmologist services are government-insured but services provided by
      optometrists are not, on eye care utilization and eye disease detection and
      treatment. We aimed to address this question by examining geographic variations
      in eye care service utilization on Prince Edward Island (PEI). METHODS: PEI
      physician-billing data from 2010 to 2012 was analyzed across five distinct
      geographic regions (Charlottetown, Summerside, Prince, Queens & Kings and
      Stratford). The residential location of patients and practice locations of eye
      care providers were identified using the first three digits of their respective
      postal code. Age-standardized rates were computed for comparisons across
      different regions. RESULTS: There were six ophthalmologists practicing on PEI,
      five with offices in Charlottetown. Twenty optometrists practiced on the island
      with offices across the province. Stratford is closest and Prince farthest from
      Charlottetown. Age-standardized utilization rates of ophthalmologists per 100
      populations were 10.44 in Charlottetown and 10.90 in Stratford, which was
      significantly higher than in other regions (7.74-8.92; p < 0.05). The disparities
      were most pronounced amongst the elderly. The prevalence of glaucoma visits was
      higher in Charlottetown (6.10%) and Stratford (6.38%) and lower in other regions.
      A similar pattern was observed for the prevalence of cataract visits. While the
      prevalence of diabetes visits was higher in Prince and Summerside, the
      utilization of ophthalmologists by people with diabetes was almost twice as high
      in Charlottetown (6.49%) than in Prince (3.88%). CONCLUSIONS: The observed
      discrepancies in vision care utilization across geographic regions were likely
      attributed to barriers in accessing government-insured, geographically
      concentrated ophthalmologists, as opposed to a reflection of the true differences
      in eye disease occurrence. The lower prevalence of glaucoma visits in regions
      farther away from ophthalmologist offices may result in delayed detection and
      blindness in this population. Encouraging ophthalmologists to work in other areas
      of the province and/or to publicly fund services provided by optometrists may
      mitigate the observed disparities. TRIAL REGISTRATION: Not applicable.

PMID- 29636057
TI  - A case of complete splenic infarction after laparoscopic spleen-preserving distal
      pancreatectomy.
AB  - BACKGROUND: Laparoscopic spleen-preserving distal pancreatectomy (LSPDP), a newly
      developed operative procedure, is indicated for benign and low-grade malignant
      disease of the pancreas. However, few studies have reported on postoperative
      splenic infarction after LSPDP. CASE PRESENTATION: We report a case of complete
      splenic infarction and obliteration of the splenic artery and vein after LSPDP.
      The patient was a 69-year-old woman with a 35-mm cystic tumor of the pancreatic
      body who underwent LSPDP. Although the operation was completed with preservation
      of the splenic artery and vein, postoperative splenic infarction was revealed
      with left back pain and fluid collection around the stump of the pancreas on
      postoperative day 9. Fortunately, clinical symptoms disappeared within days and
      additional splenectomy was not needed. Splenic infarction was attributed to
      scattered micro-embolizations within the spleen after drawing strongly on the
      tape encircling the splenic vessels. CONCLUSION: Preserving splenic vessels in
      LSPDP is a demanding procedure. To prevent splenic infarction in LSPDP, we should
      carefully isolate the pancreatic parenchyma from the splenic vessels, and must
      avoid drawing tightly on the vessel loop encircling splenic vessels.

PMID- 29636056
TI  - From top to bottom: Cell polarity in Hedgehog and Wnt trafficking.
AB  - Spatial organization of membrane domains within cells and cells within tissues is
      key to the development of organisms and the maintenance of adult tissue. Cell
      polarization is crucial for correct cell-cell signalling, which, in turn,
      promotes cell differentiation and tissue patterning. However, the mechanisms
      linking internal cell polarity to intercellular signalling are just beginning to
      be unravelled. The Hedgehog (Hh) and Wnt pathways are major directors of
      development and their malfunction can cause severe disorders like cancer. Here we
      discuss parallel advances into understanding the mechanism of Hedgehog and Wnt
      signal dissemination and reception. We hypothesize that cell polarization of the
      signal-sending and signal-receiving cells is crucial for proper signal spreading
      and activation of the pathway and, thus, fundamental for development of
      multicellular organisms.

PMID- 29636058
TI  - Effect of continuous positive airway pressure on long-term cardiovascular
      outcomes in patients with coronary artery disease and obstructive sleep apnea: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is highly prevalent in patients with
      coronary artery disease (CAD) and is associated with recurrent cardiovascular
      risk. However, whether treatment with continuous positive airway pressure (CPAP)
      reduces this risk remains unclear. We performed a systematic review and meta
      analysis to assess the effect of CPAP on long-term cardiovascular outcomes in
      patients with concomitant CAD and OSA. METHODS: We searched the PubMed, EMBASE,
      and Cochrane library from their inceptions to October 7, 2017. We included
      observational studies and randomized controlled trials (RCTs) that described the
      association of CPAP treatment with cardiovascular events in patients with CAD and
      OSA. The primary outcome of interest was major adverse cardiovascular event
      (MACE), including all-cause or cardiovascular death, myocardial infarction,
      stroke, repeat revascularization, or hospitalization for heart failure. Outcomes
      data were pooled using random effects models and heterogeneity assessed with the
      I2 statistic. RESULTS: We identified 9 studies (2 RCTs and 7 observational
      studies) with 1430 participants. The median follow-up duration was from 36 to
      86.5 months. Treatment with CPAP was associated with a significantly lower risk
      of MACE in 6 observational studies (RR 0.61, 95% CI: 0.39-0.94, P = 0.02), but
      this was not reproduced in 2 RCTs (RR 0.57, 95% CI: 0.32-1.02, P = 0.06).
      Similarly, CPAP significantly reduced the risk of all-cause death (4
      observational studies) and cardiovascular death (3 observational studies), which
      were also not confirmed in RCTs. CONCLUSIONS: The use of CPAP in patients with
      CAD and OSA might prevent subsequent cardiovascular events, which was only
      demonstrated in observational studies, but not in RCTs. The value of CPAP therapy
      as second prevention for CAD needs further investigation.

PMID- 29636059
TI  - beta-arrestin2 functions as a key regulator in the sympathetic-triggered
      immunodepression after stroke.
AB  - BACKGROUND: Stroke-induced immunodeficiency syndrome (SIDS) is regarded as a
      protective mechanism for secondary inflammatory injury as well as a contributor
      to infection complications. Although stroke-induced hyperactivation of the
      sympathetic system is proved to facilitate SIDS, the involved endogenous factors
      and pathways are largely elusive. In this study, we aim to investigate the
      function of beta-arrestin-2 (ARRB2) in the sympathetic-mediated SIDS. METHODS:
      Splenic ARRB2 expression and the sympathetic system activity were detected after
      establishing transient models of middle cerebral artery occlusion (MCAO). In
      addition, a correlation between ARRB2 expression and the sympathetic system
      activity was analyzed using a linear correlation analysis. Any SIDS reflected in
      monocyte dysfunction was investigated by measuring inflammatory cytokine
      secretion and neurological deficit scores and infarct volume were tested to
      assess neurological outcome. Further, ARRB2 expression in the monocytes was
      knocked down in vitro by siRNAs. Following the stimulation of noradrenaline and
      lipopolysaccharide, cytokine secretion and the nuclear factor-kappaB (NF-kappaB)
      pathway were evaluated to gain insight into the mechanisms related to the
      contribution of ARRB2 to adrenergic-induced monocyte dysfunction. RESULTS:
      Splenic ARRB2 expression was significantly increased after stroke and also showed
      a significant positive correlation with the sympathetic system activity. Stroke
      induced monocyte dysfunction resulted in an increase of the interleukin-10 (IL
      10) level as well as a decrease of the interleukin-6 (IL-6), tumor necrosis
      factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) levels. Also, blockade
      of adrenergic-activity significantly reversed these cytokine levels, and blockade
      of adrenergic-activity improved stroke-induced neurological results. However, the
      improved neurological results had no significant correlation with ARRB2
      expression. Furthermore, the in vitro results showed that the deficiency of ARRB2
      dramatically repealed adrenergic-induced monocyte dysfunction and the inhibition
      of NF-kappaB signaling phosphorylation activity. CONCLUSIONS: ARRB2 is implicated
      in the sympathetic-triggered SIDS, in particular, monocyte dysfunction after
      stroke. Accordingly, ARRB2 may be a promising therapeutic target for the
      immunological management of stroke in a clinic.

PMID- 29636060
TI  - Effects of apoC1 genotypes on the hormonal levels, metabolic profile and PAF-AH
      activity in Chinese women with polycystic ovary syndrome.
AB  - BACKGROUND: Elevated serum levels of apolipoprotein (apo) C1 may be an early
      protein marker of metabolic abnormality in women with polycystic ovary syndrome
      (PCOS). It is not clear, however, whether there are any relationships between the
      apoC1 rs4420638A/G and -317deletion (H1)/insertion (H2) polymorphisms and PCOS.
      We investigated the relationship between these two variants and the risk of PCOS,
      evaluated the genotypic effects on clinical, hormonal and metabolic indexes and
      plasma platelet-activating factor acetylhydrolase (PAF-AH) activity, and defined
      the association of apoC1 gene variants with apoE epsilon2/epsilon3/epsilon4
      polymorphisms. METHODS: This is a cross-sectional study of 877 women with PCOS
      and 761 controls. The apoC1 rs4420638A/G genotype was determined by a Taqman real
      time PCR allelic discrimination assay. The apoC1-317H1/H2 and apoE
      epsilon2/epsilon3/epsilon4 genotypes were measured using PCR and restriction
      fragment length polymorphism analysis. The clinical, hormonal and metabolic
      parameters and PAF-AH activity were measured. RESULTS: The frequencies of apoC1
      rs4420638A/G and -317H1/H2 genotypes and alleles were similar between PCOS and
      control groups (P > 0.05). However, the rs4420638 G allele was related to
      increased serum luteinizing hormone, cholesterol and apoB levels, and the ratio
      of apoB to apoA1 (P < 0.05), and the -317H1H1 genotype was associated with a
      higher acne grade score and a higher ratio of apoB-PAF-AH to H-PAF-AH activity (P
      < 0.05) in patients with PCOS. We also demonstrated that the apoC1 rs4420638A/G
      and -317H1/H2 gene variants existed in moderate to reasonably high linkage
      disequilibrium with apoE epsilon2/epsilon3/epsilon4 polymorphisms in Chinese
      women. CONCLUSION: The apoC1 rs4420638A/G and -317H1/H2 gene variants might be
      involved in endocrine abnormalities of reproductive axis, metabolic abnormalities
      and chronic inflammation in PCOS, although no association was observed between
      the apoC1 genetic variants and the risk of PCOS in Chinese women.

PMID- 29636061
TI  - SIRT1 overexpression is an independent prognosticator for patients with
      esophageal squamous cell carcinoma.
AB  - BACKGROUND: Sirtuin 1 (SIRT1) regulates DNA repair and metabolism by
      deacetylating target proteins. SIRT1 may be oncogenic because its overexpression
      has been detected in many cancers. The aim of the present study was to clarify
      the prognostic role of SIRT1 in patients with esophageal squamous cell carcinoma
      (ESCC) and evaluate the effect of SIRT1 inhibitor in vitro. METHODS: The
      expression of SIRT1 was evaluated immunohistochemically in 155 surgically
      resected ESCC and the staining results were evaluated semiquantitatively by the
      Immunoreactive Scoring System. The clinical features and treatment outcome were
      analyzed. The effect of SIRT1 inhibitor, SIRT 1 inhibitor IV, (S)-35, was
      investigated in vitro on ESCC cell lines. RESULTS: The expression of SIRT1 on
      ESCC did not correlate with age, gender, tumor location, stage, T classification,
      N classification, surgical margin or histology. Univariate analysis showed that
      SIRT1 overexpression was associated with inferior overall survival (P = 0.004)
      and disease-free survival (P = 0.004). In multivariate comparison, SIRT1
      overexpression remained independently associated with worse overall survival (P =
      0.009, hazard ratio = 1.776) and disease-free survival (P = 0.017, hazard ratio =
      1.642). In cell lines, SIRT1 inhibitor inhibited ESCC growth. CONCLUSIONS: Our
      study suggests that SIRT1 overexpression is an independent prognosticator for
      patients with ESCC and the SIRT1 inhibitor suppressed cell proliferation of ESCC
      cell lines. Our findings suggest that inhibition of SIRT1 signaling may be a
      promising novel target for ESCC.

PMID- 29636062
TI  - Intraoperative assessment of reduction and implant placement in acetabular
      fractures-limitations of 3D-imaging compared to computed tomography.
AB  - BACKGROUND: In acetabular fractures, the assessment of reduction and implant
      placement has limitations in conventional 2D intraoperative imaging. 3D imaging
      offers the opportunity to acquire CT-like images and thus to improve the results.
      However, clinical experience shows that even 3D imaging has limitations,
      especially regarding artifacts when implants are placed. The purpose of this
      study was to assess the difference between intraoperative 3D imaging and
      postoperative CT regarding reduction and implant placement. METHODS: Twenty
      consecutive cases of acetabular fractures were selected with a complete set of
      intraoperative 3D imaging and postoperative CT data. The largest detectable step
      and the largest detectable gap were measured in all three standard planes. These
      values were compared between the 3D data sets and CT data sets. Additionally,
      possible correlations between the possible confounders age and BMI and the
      difference between 3D and CT values were tested. RESULTS: The mean difference of
      largest visible step between the 3D imaging and CT scan was 2.0 +/- 1.8 mm (0.0
      5.8, p = 0.02) in the axial, 1.3 +/- 1.4 mm (0.0-3.7, p = 0.15) in the sagittal
      and 1.9 +/- 2.4 mm (0.0-7.4, p = 0.22) in the coronal views. The mean difference
      of largest visible gap between the 3D imaging and CT scan was 3.1 +/- 3.6 mm (0.0
      14.1, p = 0.03) in the axial, 4.6 +/- 2.7 mm (1.2-8.7, p = 0.001) in the sagittal
      and 3.5 +/- 4.0 mm (0.0-15.4, p = 0.06) in the coronal views. A positive
      correlation between the age and the difference in gap measurements in the
      sagittal view was shown (rho = 0.556, p = 0.011). CONCLUSIONS: Intraoperative 3D
      imaging is a valuable adjunct in assessing reduction and implant placement in
      acetabular fractures but has limitations due to artifacts caused by implant
      material. This can lead to missed malreduction and impairment of clinical
      outcome, so postoperative CT should be considered in these cases.

PMID- 29636063
TI  - Neuregulin-1 attenuates experimental cerebral malaria (ECM) pathogenesis by
      regulating ErbB4/AKT/STAT3 signaling.
AB  - BACKGROUND: Human cerebral malaria (HCM) is a severe form of malaria
      characterized by sequestration of infected erythrocytes (IRBCs) in brain
      microvessels, increased levels of circulating free heme and pro-inflammatory
      cytokines and chemokines, brain swelling, vascular dysfunction, coma, and
      increased mortality. Neuregulin-1beta (NRG-1) encoded by the gene NRG1, is a
      member of a family of polypeptide growth factors required for normal development
      of the nervous system and the heart. Utilizing an experimental cerebral malaria
      (ECM) model (Plasmodium berghei ANKA in C57BL/6), we reported that NRG-1 played a
      cytoprotective role in ECM and that circulating levels were inversely correlated
      with ECM severity. Intravenous infusion of NRG-1 reduced ECM mortality in mice by
      promoting a robust anti-inflammatory response coupled with reduction in
      accumulation of IRBCs in microvessels and reduced tissue damage. METHODS: In the
      current study, we examined how NRG-1 treatment attenuates pathogenesis and
      mortality associated with ECM. We examined whether NRG-1 protects against CXCL10-
      and heme-induced apoptosis using human brain microvascular endothelial (hCMEC/D3)
      cells and M059K neuroglial cells. hCMEC/D3 cells grown in a monolayer and a co
      culture system with 30 MUM heme and NRG-1 (100 ng/ml) were used to examine the
      role of NRG-1 on blood brain barrier (BBB) integrity. Using the in vivo ECM
      model, we examined whether the reduction of mortality was associated with the
      activation of ErbB4 and AKT and inactivation of STAT3 signaling pathways. For
      data analysis, unpaired t test or one-way ANOVA with Dunnett's or Bonferroni's
      post test was applied. RESULTS: We determined that NRG-1 protects against cell
      death/apoptosis of human brain microvascular endothelial cells and neroglial
      cells, the two major components of BBB. NRG-1 treatment improved heme-induced
      disruption of the in vitro BBB model consisting of hCMEC/D3 and human M059K
      cells. In the ECM murine model, NRG-1 treatment stimulated ErbB4 phosphorylation
      (pErbB4) followed by activation of AKT and inactivation of STAT3, which
      attenuated ECM mortality. CONCLUSIONS: Our results indicate a potential pathway
      by which NRG-1 treatment maintains BBB integrity in vitro, attenuates ECM-induced
      tissue injury, and reduces mortality. Furthermore, we postulate that augmenting
      NRG-1 during ECM therapy may be an effective adjunctive therapy to reduce CNS
      tissue injury and potentially increase the effectiveness of current anti-malaria
      therapy against human cerebral malaria (HCM).

PMID- 29636064
TI  - Traditional Chinese and western medicine for the prevention of deep venous
      thrombosis after lower extremity orthopedic surgery: a meta-analysis of
      randomized controlled trials.
AB  - BACKGROUND: Chinese herbal medicine has traditionally been considered to promote
      blood circulation to remove obstruction in the channels and clear pathogenic heat
      to drain dampness effects. We conducted this meta-analysis to evaluate its
      benefits for the prevention of deep venous thrombosis (DVT) after lower extremity
      orthopedic surgery. METHODS: Relevant, published studies were identified using
      the following keywords: lower extremity orthopedic surgery, arthroplasty, joint
      replacement, fracture, traditional Chinese and western medicine, Chinese herbal
      medicine, deep venous thrombosis (DVT), and Venous thromboembolism (VTE). The
      following databases were used to identify the literature consisting of RCTs with
      a date of search of 31 May 2017: PubMed, Cochrane Library, Web of knowledge, the
      Chinese National Knowledge Infrastructure Database, the Chongqing VIP Database,
      the Chinese Biomedical Database, and the Wanfang Database (including three
      English and four Chinese databases). All relevant data were collected from
      studies meeting the inclusion criteria. The outcome variables were the incidence
      rate of DVT, activated partial thromboplastin time (APTT), prothrombin time (PT),
      and D-dimer; subcutaneous hematoma; and other reported outcomes. RevMan5.2.
      software was adopted for the meta-analysis. RESULTS: A total of 20 published
      studies (1862 cases) met the inclusion criteria. The experimental group, 910
      patients (48.87%), received the Chinese herbal medicine or traditional Chinese
      and western medicine for prevention of DVT; the control group, 952 patients
      (51.13%), received the standard western treatment. The meta-analysis showed that
      traditional Chinese and western medicine therapy reduced the incidence rates of
      DVT significantly when compared with controls (risk ratio [RR] = 0.40; 95% CI,
      0.30 to 0.54; P < 0.00001), and the D-dimer was lower in the experimental group
      (P = 0.01). Besides, the incidence rate of subcutaneous hematoma was lower in the
      experimental group (P < 0.0001). However, no significant difference was found in
      the PT (P = 0.98) and APTT (P = 0.75) in two groups. No serious adverse events
      were reported. CONCLUSION: Traditional Chinese and western medicine therapy may
      be a safe, effective prevention modality for DVT after lower extremity orthopedic
      surgery. Further rigorously designed, randomized trials are warranted.

PMID- 29636065
TI  - Urinary miR-196a predicts disease progression in patients with chronic kidney
      disease.
AB  - BACKGROUND: Urinary miRNAs may potentially serve as noninvasive biomarkers in
      various kidney diseases to reflect disease activity, severity and progression,
      especially those correlated with the pathogenesis of kidney diseases. This study
      demonstrates that urinary miR-196a, a kidney-enriched miRNA, can predict
      progression of chronic kidney disease (CKD). METHODS: Focal segmental
      glomerulosclerosis (FSGS) cohorts were used as the representative example of CKD.
      First, correlation of miR-196a with disease activity was analyzed using paired
      urine and plasma samples from FSGS patients with nephrotic-range proteinuria
      (FSGS-A), complete remission (FSGS-CR) and normal controls (NCs). Then, the value
      of urinary miR-196a in predicting disease progression was validated using another
      cohort of 231 FSGS patients who were followed-up until over 36 months or reaching
      end-stage renal disease (ESRD). MiR-196a levels were analyzed by quantitative
      reverse transcription-polymerase chain reaction. RESULTS: The results showed that
      urinary miR-196a significantly increased in FSGS-A compared with FSGS-CR and NCs,
      clearly distinguishing FSGS-A from FSGS-CR and NCs, whereas plasma miR-196a
      showed no difference among these groups. Moreover, urinary miR-196a, which was
      associated with proteinuria, estimated glomerular filtration rate (eGFR),
      interstitial fibrosis and tubular atrophy, significantly increased in patients
      progressed to ESRD compared to those not. Furthermore, patients with higher
      urinary miR-196a displayed poorer renal survival than those with lower urinary
      miR-196a. Multivariate Cox analysis confirmed urinary miR-196a as an independent
      risk factor for FSGS progression after adjusting for age, sex, proteinuria and
      eGFR. Prediction accuracy of ESRD was significantly improved by combining urinary
      miR-196a with other indicators including eGFR and proteinuria. CONCLUSION:
      Urinary miR-196a may serve as a biomarker for predicting CKD progression.

PMID- 29636066
TI  - Giant thymoma successfully resected via median sternotomy and anterolateral
      thoracotomy: a case report.
AB  - BACKGROUND: Some patients with thymoma present with a very large mass in the
      thoracic cavity. Although the most effective treatment for thymoma is surgical
      resection, it is difficult to perform because of the size of the tumor and the
      infiltration of tumor into the surrounding organs and vessels. We report a
      patient with a giant thymoma that was completely resected via a median sternotomy
      and left anterolateral thoracotomy. CASE PRESENTATION: A 63-year-old woman
      presented with a mass in the left thoracic cavity that was incidentally found on
      a chest X-ray. Chest computed tomography revealed a giant mass (16 * 10 cm)
      touching the chest wall and diaphragm and pressed against the heart and left
      upper pulmonary lobe. Complete resection was performed via a median sternotomy
      and left anterolateral thoracotomy. The tumor was histologically diagnosed as a
      WHO type B2 thymoma, Masaoka stage II. CONCLUSIONS: Giant thymomas tend to grow
      expansively without invasion into surrounding organs and vessels. Surgical
      resection that employs an adequate approach must be considered, regardless of the
      size of the tumor.

PMID- 29636067
TI  - A novel neuregulin - jagged1 paracrine loop in breast cancer transendothelial
      migration.
AB  - BACKGROUND: The interaction of breast cancer cells with other cells in the tumor
      microenvironment plays an important role in metastasis. Invasion and
      intravasation, two critical steps in the metastatic process, are influenced by
      these interactions. Macrophages are of particular interest when it comes to
      studying tumor cell invasiveness. Previous studies have shown that there is
      paracrine loop signaling between breast cancer cells and macrophages involving
      colony stimulating factor 1 (CSF-1) produced by tumor cells and epidermal growth
      factor (EGF) production by macrophages. In this paper, we identify a novel
      paracrine loop between tumor cells and macrophages involving neuregulin (NRG1)
      and notch signaling. METHODS: The aim of this study was to determine the role of
      NRG1, a ligand of the ErbB3 receptor, in macrophage stimulation of tumor cell
      transendothelial migration and intravasation. We used fluorescence-activated cell
      sorting (FACS) and western blot to determine ErbB3 and NRG1 expression,
      respectively. An in vitro transendothelial migration (iTEM) assay was used to
      examine the effects of short hairpin (sh)RNA targeting NRG1 in tumor cells and
      clustered regularly interspaced short palindromic repeats (CRISPR) knockout of
      jagged 1 (JAG1) in macrophages. Orthotopic xenograft injections in mice were used
      to confirm results in vivo. RESULTS: In our system, macrophages were the primary
      cells showing expression of ErbB3, and a blocking antibody against ErbB3 resulted
      in a significant decrease in macrophage-induced transendothelial migration of
      breast cancer cells. Stimulation of macrophages with NRG1 upregulated mRNA and
      protein expression of JAG1, a ligand of the Notch receptor, and JAG1 production
      by macrophages was important for transendothelial migration of tumor cells.
      CONCLUSIONS: This study demonstrates that stimulation of macrophages by tumor
      cell NRG1 can enhance transendothelial migration and intravasation. We also
      demonstrate that this effect is due to induction of macrophage JAG1, an important
      ligand of the Notch signaling pathway.

PMID- 29636068
TI  - Iron-dependent cell death as executioner of cancer stem cells.
AB  - This commentary highlights the findings by Mai, et al. that ironomycin,
      derivatives of salinomycin, exhibited more potent and selective therapeutic
      activity against breast cancer stem cells by accumulating and sequestering iron
      in lysosome, followed by an iron-mediated lysosomal production of reactive oxygen
      species and an iron-dependent cell death. These unprecedented findings identified
      iron homeostasis and iron-mediated processes as potentially druggable in the
      context of cancer stem cells.

PMID- 29636070
TI  - Neural correlates of interference resolution in the multi-source interference
      task: a meta-analysis of functional neuroimaging studies.
AB  - BACKGROUND: Interference resolution refers to cognitive control processes
      enabling one to focus on task-related information while filtering out unrelated
      information. But the exact neural areas, which underlie a specific cognitive task
      on interference resolution, are still equivocal. The multi-source interference
      task (MSIT), as a particular cognitive task, is a well-established experimental
      paradigm used to evaluate interference resolution. Studies combining the MSIT
      with functional magnetic resonance imaging (fMRI) have shown that the MSIT evokes
      the dorsal anterior cingulate cortex (dACC) and cingulate-frontal-parietal
      cognitive-attentional networks. However, these brain areas have not been
      evaluated quantitatively and these findings have not been replicated. METHODS: In
      the current study, we firstly report a voxel-based meta-analysis of functional
      brain activation associated with the MSIT so as to identify the localization of
      interference resolution in such a specific cognitive task. Articles on MSIT
      related fMRI published between 2003 and July 2017 were eligible. The electronic
      databases searched included PubMed, Web of Knowledge, and Google Scholar.
      Differential BOLD activation patterns between the incongruent and congruent
      condition were meta-analyzed in anisotropic effect-size signed differential
      mapping software. RESULTS: Robustness meta-analysis indicated that two
      significant activation clusters were shown to have reliable functional activity
      in comparisons between incongruent and congruent conditions. The first reliable
      activation cluster, which included the dACC, medial prefrontal cortex,
      supplementary motor area, replicated the previous MSIT-related fMRI study
      results. Furthermore, we found another reliable activation cluster comprising
      areas of the right insula, right inferior frontal gyrus, and right lenticular
      nucleus-putamen, which were not typically discussed in previous MSIT-related fMRI
      studies. CONCLUSIONS: The current meta-analysis study presents the reliable brain
      activation patterns on MSIT. These findings suggest that the cingulate-frontal
      striatum network and right insula may allow control demands to resolve
      interference on MSIT. These results provide new insights into the neural
      mechanisms underlying interference resolution.

PMID- 29636071
TI  - A better start for health equity? Qualitative content analysis of implementation
      of extended postnatal home visiting in a disadvantaged area in Sweden.
AB  - BACKGROUND: Health inequities among children in Sweden persist despite the
      country's well-developed welfare system and near universal access to the national
      child health care programme. A multisectoral extended home visiting intervention,
      based on the principles of proportionate universalism, has been carried out in a
      disadvantaged area since 2013. The present study investigates the content of the
      meetings between families and professionals during the home visits to gain a
      deeper understanding of how it relates to a health equity perspective on early
      childhood development. METHODS: Three child health care nurses documented 501
      visits to the families of 98 children between 2013 and 2016. A qualitative data
      driven conventional content analysis was performed on all data from the cycle of
      six visits per child, and a general content model was developed. Additional
      content analysis was carried out on the data from visits to families who
      experienced adverse situations or greater needs. RESULTS: The analysis revealed
      that the home visits covered three main categories of content related to the
      health, care and development of the child; the strengthening of roles and
      relations within the new family unit; and the influence and support located in
      the broader external context around the family. The model of categories and sub
      categories proved stable over all six visits. Families with extra needs received
      continuous attention to their additional issues during the visits, as well as the
      standard content described in the content model. CONCLUSIONS: This study on home
      visiting implementation indicates that the participating families received
      programme content which covered all the domains of nurturing care as recommended
      by the WHO Commission on Social Determinants of Health and recent research. The
      content of the home visits can be understood to create enabling conditions for
      health equity effects. The intervention can be seen to represent a practical
      example of proportionate universalism.

PMID- 29636069
TI  - New World feline APOBEC3 potently controls inter-genus lentiviral transmission.
AB  - BACKGROUND: The apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3
      (APOBEC3; A3) gene family appears only in mammalian genomes. Some A3 proteins can
      be incorporated into progeny virions and inhibit lentiviral replication. In turn,
      the lentiviral viral infectivity factor (Vif) counteracts the A3-mediated
      antiviral effect by degrading A3 proteins. Recent investigations have suggested
      that lentiviral vif genes evolved to combat mammalian APOBEC3 proteins, and have
      further proposed that the Vif-A3 interaction may help determine the co
      evolutionary history of cross-species lentiviral transmission in mammals.
      RESULTS: Here we address the co-evolutionary relationship between two New World
      felids, the puma (Puma concolor) and the bobcat (Lynx rufus), and their
      lentiviruses, which are designated puma lentiviruses (PLVs). We demonstrate that
      PLV-A Vif counteracts the antiviral action of APOBEC3Z3 (A3Z3) of both puma and
      bobcat, whereas PLV-B Vif counteracts only puma A3Z3. The species specificity of
      PLV-B Vif is irrespective of the phylogenic relationships of feline species in
      the genera Puma, Lynx and Acinonyx. We reveal that the amino acid at position 178
      in the puma and bobcat A3Z3 is exposed on the protein surface and determines the
      sensitivity to PLV-B Vif-mediated degradation. Moreover, although both the puma
      and bobcat A3Z3 genes are polymorphic, their sensitivity/resistance to PLV Vif
      mediated degradation is conserved. CONCLUSIONS: To the best of our knowledge,
      this is the first study suggesting that the host A3 protein potently controls
      inter-genus lentiviral transmission. Our findings provide the first evidence
      suggesting that the co-evolutionary arms race between lentiviruses and mammals
      has occurred in the New World.

PMID- 29636072
TI  - Deciphering viral presences: two novel partial giant viruses detected in marine
      metagenome and in a mine drainage metagenome.
AB  - Nucleo-cytoplasmic large DNA viruses are doubled stranded DNA viruses capable of
      infecting eukaryotic cells. Since the discovery of Mimivirus and Pandoravirus,
      there has been no doubt about their extraordinary features compared to "classic"
      viruses. Recently, we reported the expansion of the proposed family Pithoviridae,
      with the description of Cedratvirus and Orpheovirus, two new viruses related to
      Pithoviruses. Studying the major capsid protein of Orpheovirus, we detected a
      homologous sequence in a mine drainage metagenome. The in-depth exploration of
      this metagenome, using the MG-Digger program, enabled us to retrieve up to 10
      contigs with clear evidence of viral sequences. Moreover, phylogenetic analyses
      further extended our screening with the discovery in another marine metagenome of
      a second virus closely related to Orpheovirus IHUMI-LCC2. This virus is a
      misidentified virus confused with and annotated as a Rickettsiales bacterium. It
      presents a partial genome size of about 170 kbp.

PMID- 29636073
TI  - Vast diversity of prokaryotic virus genomes encoding double jelly-roll major
      capsid proteins uncovered by genomic and metagenomic sequence analysis.
AB  - BACKGROUND: Analysis of metagenomic sequences has become the principal approach
      for the study of the diversity of viruses. Many recent, extensive metagenomic
      studies on several classes of viruses have dramatically expanded the visible part
      of the virosphere, showing that previously undetected viruses, or those that have
      been considered rare, actually are important components of the global virome.
      RESULTS: We investigated the provenance of viruses related to tail-less
      bacteriophages of the family Tectiviridae by searching genomic and metagenomics
      sequence databases for distant homologs of the tectivirus-like Double Jelly-Roll
      major capsid proteins (DJR MCP). These searches resulted in the identification of
      numerous genomes of virus-like elements that are similar in size to tectiviruses
      (10-15 kilobases) and have diverse gene compositions. By comparison of the gene
      repertoires, the DJR MCP-encoding genomes were classified into 6 distinct groups
      that can be predicted to differ in reproduction strategies and host ranges. Only
      the DJR MCP gene that is present by design is shared by all these genomes, and
      most also encode a predicted DNA-packaging ATPase; the rest of the genes are
      present only in subgroups of this unexpectedly diverse collection of DJR MCP
      encoding genomes. Only a minority encode a DNA polymerase which is a hallmark of
      the family Tectiviridae and the putative family "Autolykiviridae". Notably, one
      of the identified putative DJR MCP viruses encodes a homolog of Cas1
      endonuclease, the integrase involved in CRISPR-Cas adaptation and integration of
      transposon-like elements called casposons. This is the first detected occurrence
      of Cas1 in a virus. Many of the identified elements are individual contigs
      flanked by inverted or direct repeats and appear to represent complete,
      extrachromosomal viral genomes, whereas others are flanked by bacterial genes and
      thus can be considered as proviruses. These contigs come from metagenomes of
      widely different environments, some dominated by archaea and others by bacteria,
      suggesting that collectively, the DJR MCP-encoding elements have a broad host
      range among prokaryotes. CONCLUSIONS: The findings reported here greatly expand
      the known host range of (putative) viruses of bacteria and archaea that encode a
      DJR MCP. They also demonstrate the extreme diversity of genome architectures in
      these viruses that encode no universal proteins other than the capsid protein
      that was used as the marker for their identification. From a supposedly minor
      group of bacterial and archaeal viruses, these viruses are emerging as a
      substantial component of the prokaryotic virome.

PMID- 29636074
TI  - LncRNA H19 contributes to hippocampal glial cell activation via JAK/STAT
      signaling in a rat model of temporal lobe epilepsy.
AB  - BACKGROUND: Astrocyte and microglia activation are well-known features of
      temporal lobe epilepsy that may contribute to epileptogenesis. However, the
      mechanisms underlying glia activation are not well understood. Long non-coding
      RNA (lncRNA) H19 has diverse functions depending on physiological or pathological
      state, and its role in epilepsy is unknown. We previously demonstrated that H19
      was significantly upregulated in the latent period of epilepsy and may be
      associated with cell proliferation and immune and inflammatory responses. We
      therefore speculated that H19 is involved in the hippocampal glial cell
      activation during epileptogenesis. METHODS: H19 was overexpressed or knocked down
      using an adeno-associated viral vector delivery system. A rat status epilepticus
      model was induced by intra-amygdala kainic acid injection. Astrocyte and
      microglia activation were assessed by immunofluorescence and western blot
      analyses. Expression of proinflammatory cytokines and components of the Janus
      kinase (JAK)/signal transducer and activator of transcription (STAT) signaling
      pathways were evaluated with western blotting. RESULTS: H19 overexpression
      induced the activation of astrocytes and microglia and the release of
      proinflammatory cytokines (interleukin-1beta and interleukin-6 and tumor necrosis
      factor-alpha) in the hippocampus, whereas H19 knockdown inhibited status
      epilepticus-induced glial cell activation. Moreover, H19 activated JAK/STAT
      signaling by promoting the expression of Stat3 and c-Myc, which is thought to be
      involved in astrocyte activation. CONCLUSIONS: LncRNA H19 contributes to
      hippocampal glial cell activation via modulation of the JAK/STAT pathway and
      could be a therapeutic tool to prevent the development of epilepsy.

PMID- 29636075
TI  - Identification of lncRNA expression profiles and ceRNA analysis in the spinal
      cord of morphine-tolerant rats.
AB  - Morphine tolerance is a challenging clinical problem that limits the use of
      morphine in pain treatment, but the mechanisms of morphine tolerance remain
      unclear. Recent research indicates that long noncoding RNAs (lncRNAs) might be a
      novel and promising target in the pathogeneses of diseases. Therefore, we
      hypothesized that lncRNAs might play a role in the development of morphine
      tolerance. Male Sprague-Dawley rats were intrathecally injected with 10 MUg
      morphine twice daily for 7 consecutive days. The animals were then sacrificed for
      lncRNA microarray tests, and the results were validated by RT-qPCR. Next,
      functional predictions for the differentially expressed mRNAs (DEmRNAs) were made
      with the Gene Ontology/Kyoto Encyclopedia of Genes and Genomes (GO/KEGG), and
      predictions for the differentially expressed lncRNAs (DElncRNAs) were made based
      on competitive endogenous RNA (ceRNA) analyses. The rats successfully developed
      morphine tolerance. LncRNA microarray analysis revealed that, according to the
      criteria of a log2 (fold change) > 1.5 and a P-value < 0.05, 136 lncRNAs and 278
      mRNAs were differentially expressed in the morphine tolerance group (MT) compared
      with the normal saline group (NS). The functions of the DEmRNAs likely involve in
      the processes of the ion channel transport, pain transmission and immune
      response. The ceRNA analysis indicated that several possible interacting networks
      existed, including (MRAK150340, MRAK161211)/miR-219b/Tollip.Further annotations
      of the potential target mRNAs of the miRNAs according to the gene database
      suggested that the possible functions of these mRNAs primarily involved the
      regulation of ubiquitylation, G protein-linked receptors, and Toll-like
      receptors, which play roles in the development of morphine tolerance. Our
      findings revealed the profiles of differentially expressed lncRNAs in morphine
      tolerance conditions, and among these lncRNAs, some DElncRNAs might be new
      therapeutic targets for morphine tolerance.

PMID- 29636076
TI  - GAD65 autoantibody characteristics in patients with co-occurring type 1 diabetes
      and epilepsy may help identify underlying epilepsy etiologies.
AB  - BACKGROUND: Autoantibodies against the smaller isoform of glutamate decarboxylase
      (GAD65Ab) reflect autoimmune etiologies in Type 1 diabetes (T1D) and several
      neurological disorders, including Stiff Person Syndrome (SPS). GAD65Ab are also
      reported in cases of epilepsy, indicating an autoimmune component. GAD65Ab in
      patients with co-occurring T1D, epilepsy or SPS may be part of either autoimmune
      pathogenesis. To dissect the etiologies associated with GAD65Ab, we analyzed
      GAD65Ab titer, epitope specificity and enzyme inhibition in GAD65Ab-positive
      patients diagnosed with epilepsy (n = 28), patients with epilepsy and T1D (n =
      10), patients with SPS (n = 20), and patients with T1D (n = 42). RESULTS: GAD65Ab
      epitope pattern in epilepsy differed from T1D and SPS patients. Four of 10
      patients with co-occurring T1D and epilepsy showed GAD65Ab profiles similar to
      T1D patients, while lacking GAD65Ab characteristics found in GAD65Ab-positive
      epilepsy patients. One of these patients responded well to anti-epileptic drugs
      (AEDs), while another patient did not require medication for seizure control. The
      third patient was refractory due to a diagnosis of meningioma. The response of
      the remaining patient to AEDs was unknown. GAD65Ab in the remaining six patients
      with T1D and epilepsy showed profiles similar to those in epilepsy patients.
      CONCLUSIONS: Different autoimmune responses associated with T1D, epilepsy and SPS
      are reflected by disease-specific GAD65Ab patterns. Moreover, the epileptic
      etiology in patients diagnosed with both T1D and epilepsy may present two
      different etiologies regarding their epileptic condition. In one group T1D co
      occurs with non-autoimmune epilepsy. In the other group GAD65Ab are part of an
      autoimmune epileptic condition.

PMID- 29636078
TI  - Bat lung epithelial cells show greater host species-specific innate resistance
      than MDCK cells to human and avian influenza viruses.
AB  - BACKGROUND: With the recent discovery of novel H17N10 and H18N11 influenza viral
      RNA in bats and report on high frequency of avian H9 seroconversion in a species
      of free ranging bats, an important issue to address is the extent bats are
      susceptible to conventional avian and human influenza A viruses. METHOD: To this
      end, three bat species (Eidolon helvum, Carollia perspicillata and Tadarida
      brasiliensis) of lung epithelial cells were separately infected with two avian
      and two human influenza viruses to determine their relative host innate immune
      resistance to infection. RESULTS: All three species of bat cells were more
      resistant than positive control Madin-Darby canine kidney (MDCK) cells to all
      four influenza viruses. TB1-Lu cells lacked sialic acid alpha2,6-Gal receptors
      and were most resistant among the three bat species. Interestingly, avian viruses
      were relatively more replication permissive in all three bat species of cells
      than with the use of human viruses which suggest that bats could potentially play
      a role in the ecology of avian influenza viruses. Chemical inhibition of the JAK
      STAT pathway in bat cells had no effect on virus production suggesting that type
      I interferon signalling is not a major factor in resisting influenza virus
      infection. CONCLUSION: Although all three species of bat cells are relatively
      more resistant to influenza virus infection than control MDCK cells, they are
      more permissive to avian than human viruses which suggest that bats could have a
      contributory role in the ecology of avian influenza viruses.

PMID- 29636077
TI  - Clinical value of miR-182-5p in lung squamous cell carcinoma: a study combining
      data from TCGA, GEO, and RT-qPCR validation.
AB  - BACKGROUND: MiR-182-5p, as a member of miRNA family, can be detected in lung
      cancer and plays an important role in lung cancer. To explore the clinical value
      of miR-182-5p in lung squamous cell carcinoma (LUSC) and to unveil the molecular
      mechanism of LUSC. METHODS: The clinical value of miR-182-5p in LUSC was
      investigated by collecting and calculating data from The Cancer Genome Atlas
      (TCGA) database, the Gene Expression Omnibus (GEO) database, and real-time
      quantitative polymerase chain reaction (RT-qPCR). Twelve prediction platforms
      were used to predict the target genes of miR-182-5p. Protein-protein interaction
      (PPI) networks and gene ontology (GO), and Kyoto Encyclopedia of Genes and
      Genomes (KEGG) analyses were used to explore the molecular mechanism of LUSC.
      RESULTS: The expression of miR-182-5p was significantly over-expressed in LUSC
      than in non-cancerous tissues, as evidenced by various approaches, including the
      TCGA database, GEO microarrays, RT-qPCR, and a comprehensive meta-analysis of 501
      LUSC cases and 148 non-cancerous cases. Furthermore, a total of 81 potential
      target genes were chosen from the union of predicted genes and the TCGA database.
      GO and KEGG analyses demonstrated that the target genes are involved in pathways
      related to biological processes. PPIs revealed the relationships between these
      genes, with EPAS1, PRKCE, NR3C1, and RHOB being located in the center of the PPI
      network. CONCLUSIONS: MiR-182-5p upregulation greatly contributes to LUSC and may
      serve as a biomarker in LUSC.

PMID- 29636079
TI  - DACH1 antagonizes CXCL8 to repress tumorigenesis of lung adenocarcinoma and
      improve prognosis.
AB  - BACKGROUND: C-X-C motif ligand 8 (CXCL8), known as a proinflammatory chemokine,
      exerts multiple effects on the proliferation, invasion, and migration of tumor
      cells via the autocrine or paracrine manner. Conversely, the human Dachshund
      homologue 1 (DACH1) is recognized as a tumor suppressor which retards the
      progression of various cancers. In prostate cancer, it has been demonstrated that
      DACH1 was negatively correlated with the expression of CXCL8 and able to
      antagonize the effects of CXCL8 on cellular migration. Herein, we explored the
      mechanisms by which DACH1 regulated the CXCL8 in non-small cell lung cancer
      (NSCLC). METHODS: Public microarray and Kaplan-Meier plotter datasets were
      analyzed. Blood serum samples from lung adenocarcinoma (ADC) patients were
      collected for enzyme-linked immunosorbent assay (ELISA) analysis.
      Immunohistochemical staining was conducted on tissue microarray. Cell lines with
      stable expression of DACH1 were established, and relative gene expression was
      measured by Western blot, ELISA, real-time PCR, and human cytokine array.
      Correspondingly, cell lines transfected with shDACH1 were established, and
      relative gene expression was measured by real-time PCR and immunofluorescence
      array. Functional studies were performed by transwell and xenograft mice models.
      Luciferase reporter gene assay was applied to measure the regulation of DACH1 on
      CXCL8. RESULTS: Our study indicated that CXCL8 both at the mRNA and protein level
      was associated with the high tumor burden of ADC. Correlational analyses in ADC
      cell lines and ADC tissues showed that DACH1 was inversely correlated with CXCL8.
      Meanwhile, patients with high DACH1 expression and low CXCL8 expression had
      prolonged time to death and recurrence. Moreover, we verified the inhibitory
      effects of DACH1 on CXCL8 both in vitro and in vivo. Mechanism studies proved
      that DACH1 transcriptionally repressed CXCL8 promoter activity through activator
      protein-1 (AP-1) and nuclear transcription factor-kappa B (NF-kappaB) sites.
      CONCLUSIONS: Our study proved that CXCL8 acted as an unfavorable factor promoting
      to tumor progression and poor prognosis of ADC, while DACH1 antagonized CXCL8 to
      provide a favorable survival of ADC patients. Double detection of DACH1 and CXCL8
      may provide a precise information for further evaluating the prognosis of ADC
      patients.

PMID- 29636080
TI  - Transparency in ovarian cancer clinical trial results: ClinicalTrials.gov versus
      PubMed, Embase and Google scholar.
AB  - BACKGROUND: In recent years the question of the lack of transparency in clinical
      research has been debated by clinicians, researchers, citizens and their
      representatives, authors and publishers. This is particularly important for
      infrequent cancers such as ovarian cancer, where treatment still gives
      disappointing results in the majority of cases. Our aim was to assess the
      availability to the public of results in ClinicalTrials.gov, and the frequency of
      non-publication of results in ClinicalTrials.gov and in PubMed, Embase and Google
      Scholar. We collected all trials on ovarian cancer identified as "completed
      status" in the ClinicalTrials.gov registry on 17 January 2017. We checked the
      availability of the results in ClinicalTrials.gov and systematically identified
      published manuscripts on results. RESULTS: Out of 2725 trials on ovarian cancer
      identified, 752 were classified as "completed status". In those closed between
      2008 and 2015, excluding phase I, the frequency of results in ClinicalTrials.gov
      was 35%. Of the 752 completed studies the frequency of published results in
      PubMed, Embase or Google Scholar ranged from 57.9% to 69.7% in the last years.
      CONCLUSIONS: These findings show a lack of transparency and credibility of
      research. Citizens or patients' representatives, with the medical community,
      should continuously support initiatives to improve the publication and
      dissemination of clinical study results.

PMID- 29636081
TI  - Pregnancy outcomes of PCOS overweight/obese patients after controlled ovarian
      stimulation with the GnRH antagonist protocol and frozen embryo transfer.
AB  - BACKGROUND: Overweight/obese women with polycystic ovary syndrome (PCOS) are at
      increased risk of subfertility and complications of pregnancy, compared with
      normal-weight women. To implement controlled ovarian hyperstimulation (COH), the
      improved efficacy of the gonadotrophin-releasing hormone antagonist (GnRH-ant)
      protocol has been demonstrated, as well as frozen embryo transfer (FET).
      OBJECTIVE: This retrospective study evaluated the pregnancy outcomes after
      combined GnRH-ant protocol and FET in overweight/obese women with PCOS, with
      reference to that of normal-weight women with PCOS. METHODS: Women with PCOS (n =
      398) who underwent the GnRH-ant protocol for COH followed by FET, were stratified
      as normal-weight (BMI < 24 kg/m2) or overweight/obese (BMI >=24 kg/m2). The
      outcomes of pregnancy were compared. RESULTS: The overweight/obese patients had
      significantly lower rates of embryo implantation (47.7%), live birth (47.8%), and
      live births of twins (10.9%) compared with the normal-weight group (58.4%, 60.8%,
      and 30.0%, respectively; P = 0.006, 0.015, and 0.000), while the rate of late
      abortion was significantly higher (11.0% cf. 3.8%, P = 0.030). BMI was the only
      significant factor affecting the probability of live birth. CONCLUSION: The
      pregnancy outcomes of overweight/obese women with PCOS after COH via the GnRH-ant
      protocol and FET remained at a significant deficit compared with that of normal
      weight women with PCOS.

PMID- 29636082
TI  - Identification of novel biomarker as citrullinated inter-alpha-trypsin inhibitor
      heavy chain 4, specifically increased in sera with experimental and rheumatoid
      arthritis.
AB  - BACKGROUND: Anticitrullinated protein antibodies (ACPA) and citrullinated
      proteins play key roles in the pathogenesis of rheumatoid arthritis (RA). Many
      candidate citrullinated antigens have been identified in joints, but
      citrullinated proteins in sera are mostly uncertain in patients with RA. We
      explored the expression of citrullinated proteins in joints and sera of
      experimental arthritis, and we further investigated their specific expression
      correlated with the disease activity in patients with RA. METHODS: Citrullinated
      protein expression in tissues was examined by IHC in peptide glucose-6-phosphate
      isomerase-induced arthritis (pGIA). Serum citrullinated proteins from pGIA were
      examined by Western blotting, and the sequence was identified by MS. With the
      same methods, serum citrullinated proteins were analyzed in patients with RA,
      primary Sjogren's syndrome, systemic lupus erythematosus, and osteoarthritis as
      well as in healthy subjects, by Western blotting and MS. In patients with RA, the
      relationship between the expression of the identified protein (inter-alpha
      trypsin inhibitor heavy chain 4 [ITIH4]) and clinical features was evaluated, and
      the levels of citrullinated ITIH4 were compared before and after biological
      treatment. The antibody response against citrullinated ITIH4 peptide was measured
      by enzyme-linked immunosorbent assay. RESULTS: Citrullinated proteins were
      detected specifically in arthritic joints and sera from pGIA relative to
      controls. In sera, a common band of citrullinated protein at 120 kDa was
      revealed, and it fluctuated in parallel with arthritis score of pGIA by Western
      blotting. Interestingly, in 82% of RA patient sera, similar bands of
      citrullinated protein were specifically detected. These proteins were identified
      as citrullinated ITIH4, and especially the R438 site was commonly citrullinated
      between mice and humans. Citrullinated ITIH4 levels were associated with clinical
      parameters such as C-reactive protein (CRP), rheumatoid factor, and Disease
      Activity Score in 28 joints as measured by CRP in patients with RA. Its levels
      were decreased in correlation with the reduction of disease activity score after
      effective treatment in patients with RA. Moreover, antibody response to
      citrullinated epitope in ITIH4 was specifically observed in patients with RA.
      CONCLUSIONS: Our results suggest that serum citrullinated ITIH4 was specifically
      increased in patients with RA and could be a novel biomarker for assessing
      disease activity in patients with RA.

PMID- 29636083
TI  - In-feed bambermycin medication induces anti-inflammatory effects and prevents
      parietal cell loss without influencing Helicobacter suis colonization in the
      stomach of mice.
AB  - The minimum inhibitory concentration of bambermycin on three porcine Helicobacter
      suis strains was shown to be 8 MUg/mL. The effect of in-feed medication with this
      antibiotic on the course of a gastric infection with one of these strains, the
      host response and the gastric microbiota was determined in mice, as all of these
      parameters may be involved in gastric pathology. In H. suis infected mice which
      were not treated with bambermycin, an increased number of infiltrating B-cells, T
      cells and macrophages in combination with a Th2 response was demonstrated, as
      well as a decreased parietal cell mass. Compared to this non-treated, infected
      group, in H. suis infected mice medicated with bambermycin, gastric H. suis
      colonization was not altered, but a decreased number of infiltrating T-cells, B
      cells and macrophages as well as downregulated expressions of IL-1beta, IL-8M, IL
      10 and IFN-gamma were demonstrated and the parietal cell mass was not affected.
      In bambermycin treated mice that were not infected with H. suis, the number of
      infiltrating T-cells and expression of IL-1beta were lower than in non-infected
      mice that did not receive bambermycin. Gastric microbiota analysis indicated that
      the relative abundance of bacteria that might exert unfavorable effects on the
      host was decreased during bambermycin supplementation. In conclusion, bambermycin
      did not affect H. suis colonization, but decreased gastric inflammation and
      inhibited the effects of a H. suis infection on parietal cell loss. Not only
      direct interaction of H. suis with parietal cells, but also inflammation may play
      a role in death of these gastric acid producing cells.

PMID- 29636085
TI  - Population aging: opportunity for business expansion, an invitational paper
      presented at the Asia-Pacific Economic Cooperation (APEC) International Workshop
      on Adaptation to Population Aging Issues, July 17, 2017, Ha Noi, Viet Nam.
AB  - A longer life brings opportunities for older adults and their families as well as
      for their communities. Commercial businesses can be successful in innovating on
      these opportunities and achieving business expansion when they better understand
      the market dynamics and spectrum of older adults as consumers and view them more
      as assets rather than as burdens to society. While there is no "typical" older
      adult consumer, some traits, characteristics, and physical realities may be more
      common, including those related to family and community, the shopping experience,
      brand marketing and packaging, food and nutrition, and health. The opportunities
      of longer life are impacted by health and underscore the importance of positive,
      healthy aging-related behaviors like good nutrition and active lifestyles.
      Healthy aging also requires a sustained commitment and action from country
      leaders to formulate evidence-based polices--like systematic nutrition screening
      and intervention-and healthcare workforce training and education that can
      strengthen and support an active aging population. In addition, governments
      should consider engaging commercial businesses to help set sustainable policies
      that can advance products for older adults. Finally, governments should set
      national and local goals to incentivize commercial business development and
      investment in public-private partnerships to improve quality of care, promote
      healthy aging, and impact outcomes for noncommunicable diseases, ultimately
      benefitting population health for Asia-Pacific Economic Cooperation (APEC)
      countries.

PMID- 29636084
TI  - Does the presence of magnetic resonance imaging-detected osteitis at diagnosis
      with rheumatoid arthritis lower the risk for achieving disease-modifying
      antirheumatic drug-free sustained remission: results of a longitudinal study.
AB  - BACKGROUND: Although infrequent, some rheumatoid arthritis (RA) patients achieve
      disease-modifying antirheumatic drug (DMARD)-free sustained remission. The
      absence of RA-specific autoantibodies, such as anticitrullinated protein
      antibodies (ACPA), is known to be associated with this outcome but further
      mechanisms underlying the chronic nature of RA are largely unknown. Magnetic
      resonance imaging (MRI)-detected bone marrow edema (BME), or osteitis, strongly
      predicts erosive progression and is associated with ACPA positivity. Therefore,
      we hypothesized that the presence of MRI-detected osteitis is also predictive of
      not achieving DMARD-free sustained remission and that the presence of osteitis
      mediates the association between ACPA and DMARD-free sustained remission.
      METHODS: A 1.5 T unilateral hand and foot MRI was performed at disease
      presentation in 238 RA patients, evaluating BME, synovitis, and tenosynovitis
      (summed as MRI inflammation score). DMARD-free sustained remission, defined as
      the absence of clinical synovitis after DMARD cessation that persisted during the
      total follow-up, was assessed (median follow-up 3.8 years). Associations between
      the different MRI-detected inflammatory features and this outcome were studied. A
      mediation analysis was performed to study whether the presence of BME mediated
      the association between ACPA and DMARD-free sustained remission. Finally,
      patterns of MRI-detected inflammation with regard to DMARD-free sustained
      remission were studied using partial least squares (PLS) regression. RESULTS:
      Forty-six (19.3%) patients achieved DMARD-free sustained remission. ACPA
      positivity associated independently with remission (hazard ratio (HR) 0.16, 95%
      confidence interval (CI) 0.06-0.39). In contrast, no associations were observed
      between MRI-detected BME (HR 0.99, 95% CI 0.94-1.03), or other MRI inflammatory
      features, and achieving DMARD-free sustained remission. Thus, the presence of BME
      did not mediate the association between ACPA and DMARD-free sustained remission.
      Furthermore, a PLS analysis revealed that patients who did or did not achieve
      remission could not be distinguished by patterns of MRI-detected inflammation.
      CONCLUSIONS: At disease presentation, osteitis, as well as other MRI-detected
      inflammatory features, was not associated with achieving DMARD-free sustained
      remission over time. Thus, imaging predictors for joint damage and disease
      persistence differ. The processes mediating RA chronicity remain largely
      unsolved.

PMID- 29636086
TI  - Investigation into the role of the germline epigenome in the transmission of
      glucocorticoid-programmed effects across generations.
AB  - BACKGROUND: Early life exposure to adverse environments affects cardiovascular
      and metabolic systems in the offspring. These programmed effects are
      transmissible to a second generation through both male and female lines,
      suggesting germline transmission. We have previously shown that prenatal
      overexposure to the synthetic glucocorticoid dexamethasone (Dex) in rats reduces
      birth weight in the first generation (F1), a phenotype which is transmitted to a
      second generation (F2), particularly through the male line. We hypothesize that
      Dex exposure affects developing germ cells, resulting in transmissible
      alterations in DNA methylation, histone marks and/or small RNA in the male
      germline. RESULTS: We profile epigenetic marks in sperm from F1 Sprague Dawley
      rats expressing a germ cell-specific GFP transgene following Dex or vehicle
      treatment of the mothers, using methylated DNA immunoprecipitation sequencing,
      small RNA sequencing and chromatin immunoprecipitation sequencing for H3K4me3,
      H3K4me1, H3K27me3 and H3K9me3. Although effects on birth weight are transmitted
      to the F2 generation through the male line, no differences in DNA methylation,
      histone modifications or small RNA were detected between germ cells and sperm
      from Dex-exposed animals and controls. CONCLUSIONS: Although the phenotype is
      transmitted to a second generation, we are unable to detect specific changes in
      DNA methylation, common histone modifications or small RNA profiles in sperm. Dex
      exposure is associated with more variable 5mC levels, particularly at non
      promoter loci. Although this could be one mechanism contributing to the observed
      phenotype, other germline epigenetic modifications or non-epigenetic mechanisms
      may be responsible for the transmission of programmed effects across generations
      in this model.

PMID- 29636087
TI  - Intra cavernous aneurysm of internal carotid artery masquerading as a pituitary
      adenoma: a case report.
AB  - BACKGROUND: Pituitary dysfunction in adults are often associated with tumors of
      the gland and manifests with mass effects and hypopituitarism. MRI of pituitary
      region often provides confirmation of the diagnosis and assists in planning
      neurosurgery. CASE PRESENTATION: A 69 years old female evaluated for chronic
      headache was found to have a supra-sellar mass lesion that mimicked a pituitary
      tumor, with biochemical evidence of hypopituitarism. Cerebral angiogram confirmed
      the diagnosis of an aneurysm of the intracavernous internal carotid artery. She
      was successfully treated with coil embolization of the aneurysm and achieved
      resolution of symptoms and return of biochemistries to normal. CONCLUSION:
      Carotid aneurysm can mimc pituitary tumours clinically and radiologically on MRI
      scan. This rare possibility should be considered in evaluating supra-sellar
      masses to avoid catastrophic consequences.

PMID- 29636088
TI  - Prevalence of depression and anxiety among undergraduate university students in
      low- and middle-income countries: a systematic review protocol.
AB  - BACKGROUND: Depression and anxiety symptoms are reported to be common among
      university students in many regions of the world and impact on quality of life
      and academic attainment. The extent of the problem of depression and anxiety
      among students in low- and middle-income countries (LMICs) is largely unknown.
      This paper details methods for a systematic review that will be conducted to
      explore the prevalence, antecedents, consequences, and treatments for depression
      and anxiety among undergraduate university students in LMICs. METHODS: Studies
      reporting primary data on common mental disorders among students in universities
      and colleges within LMICs will be included. Quality assessment of retrieved
      articles will be conducted using four Joanna Briggs critical appraisal checklists
      for prevalence, randomized control/pseudo-randomized trials, descriptive case
      series, and comparable cohort/case control. Meta-analysis of the prevalence of
      depression and anxiety will be conducted using a random effects model which will
      generate pooled prevalence with their respective 95% confidence intervals.
      DISCUSSION: The results from this systematic review will help in informing and
      guiding healthcare practitioners, planners, and policymakers on the burden of
      common mental disorders in university students in LMICs and of appropriate and
      feasible interventions aimed at reducing the burden of psychological morbidity
      among them. The results will also point to gaps in research and help set
      priorities for future enquiries. SYSTEMATIC REVIEW REGISTRATION: PROSPERO
      CRD42017064148.

PMID- 29636090
TI  - Phenome-wide association study identifies marked increased in burden of
      comorbidities in African Americans with systemic lupus erythematosus.
AB  - BACKGROUND: African Americans with systemic lupus erythematosus (SLE) have
      increased renal disease compared to Caucasians, but differences in other
      comorbidities have not been well-described. We used an electronic health record
      (EHR) technique to test for differences in comorbidities in African Americans
      compared to Caucasians with SLE. METHODS: We used a de-identified EHR with 2.8
      million subjects to identify SLE cases using a validated algorithm. We performed
      phenome-wide association studies (PheWAS) comparing African American to Caucasian
      SLE cases and African American SLE cases to matched non-SLE controls. Controls
      were age, sex, and race matched to SLE cases. For multiple testing, a false
      discovery rate (FDR) p value of 0.05 was used. RESULTS: We identified 270 African
      Americans and 715 Caucasians with SLE and 1425 matched African American controls.
      Compared to Caucasians with SLE adjusting for age and sex, African Americans with
      SLE had more comorbidities in every organ system. The most striking included
      hypertension odds ratio (OR) = 4.25, FDR p = 5.49 * 10- 15; renal dialysis OR =
      10.90, FDR p = 8.75 * 10- 14; and pneumonia OR = 3.57, FDR p = 2.32 * 10- 8.
      Compared to the African American matched controls without SLE, African Americans
      with SLE were more likely to have comorbidities in every organ system. The most
      significant codes were renal and cardiac, and included renal failure (OR = 9.55,
      FDR p = 2.26 * 10- 40) and hypertensive heart and renal disease (OR = 8.08, FDR p
      = 1.78 * 10- 22). Adjusting for race, age, and sex in a model including both
      African American and Caucasian SLE cases and controls, SLE was independently
      associated with renal, cardiovascular, and infectious diseases (all p < 0.01).
      CONCLUSIONS: African Americans with SLE have an increased comorbidity burden
      compared to Caucasians with SLE and matched controls. This increase in
      comorbidities in African Americans with SLE highlights the need to monitor for
      cardiovascular and infectious complications.

PMID- 29636089
TI  - Comparison of the impact of Tripterygium wilfordii Hook F and Methotrexate
      treatment on radiological progression in active rheumatoid arthritis: 2-year
      follow up of a randomized, non-blinded, controlled study.
AB  - BACKGROUND: Tripterygium wilfordii Hook F (TwHF) alone or in combination with
      methotrexate (MTX) has been shown to be more effective than MTX monotherapy in
      controlling the manifestations in subjects with disease-modifying antirheumatic
      drug (DMARD)-naive active rheumatoid arthritis (RA) over a 6-month period. The
      long-term impact of these therapies on disease activity and radiographic
      progression in RA has not been examined. METHODS: Patients with DMARD-naive RA
      enrolled in the "Comparison of Tripterygium wilfordii Hook F with methotrexate in
      the Treatment of Active Rheumatoid Arthritis" (TRIFRA) study were randomly
      allocated into three arms with TwHF or MTX or the two in combination. Clinical
      indexes and radiographic data at baseline and year 2 was collected and compared
      using an intent-to-treat (ITT) and a per-protocol (PP) analysis. Two radiologists
      blinded to the treatment scored the images independently. RESULTS: Of 207
      subjects 109 completed the 2-year follow up. The number of subjects withdrawing
      from the study and the number adhering to the initial regimens were similar among
      the three groups (p > = 0.05). In the ITT analysis, proportions of patients
      reaching American College of Rheumatology 50% (ACR50) response criteria were
      46.4%, 58.0% and 50.7% in the MTX, TwHF and MTX + TwHF groups (TwHF vs MTX
      monotherapy, p = 0.004). Similar patterns were found in ACR20, ACR70, Clinical
      Disease Activity Index good responses, European League Against Rheumatism good
      response, remission rate and low disease activity rate at year 2. The results of
      the PP analysis agreed with those in the ITT analysis. The changes in total Sharp
      scores and joint erosion and joint space narrowing during the 2 years were
      associated with changes in disease activity measured by the 28-joint count
      Disease Activity Score and were comparable among the three groups (p > 0.05).
      Adverse events were similar in the three treatment groups. CONCLUSIONS: During
      the 2-year therapy period, TwHF monotherapy was not inferior to MTX monotherapy
      in controlling disease activity and retarding radiological progression in
      patients with active RA. TRIAL REGISTRATION: This is a follow-up study. Original
      trial registration: ClinicalTrials.gov , NCT01613079 . Registered on 4 June 2012.

PMID- 29636091
TI  - Dysregulated heme oxygenase-1low M2-like macrophages augment lupus nephritis via
      Bach1 induced by type I interferons.
AB  - BACKGROUND: Innate immunity including macrophages (Mphi) in lupus nephritis (LN)
      has been gaining attention, but roles of Mphi in LN remain uncertain. METHODS:
      Immunohistochemical staining was performed to determine CD68, CD163, heme
      oxygenase (HO)-1 (a stress-inducible heme-degrading enzyme with anti-inflammatory
      property), pSTAT1, and CMAF-expressing Mphi in the glomeruli of patients with LN.
      Effects of type I interferons on the expression levels of CD163, HO-1, BTB and
      CNC homology 1 (Bach1; a transcriptional HO-1 repressor), interleukin (IL)-6, and
      IL-10 by human M2-like Mphi, which were differentiated in vitro from peripheral
      monocytes with macrophage colony-stimulating factor, were assessed by RT-PCR and
      immunocytostaining. Clinical manifestations, anti-double-stranded DNA (anti
      dsDNA), and local HO-1 expression were compared in Bach1-deficient and wild-type
      MRL/lpr mice. RESULTS: The number of glomerular M2-like Mphi correlated with the
      amounts of proteinuria in patients with LN. Unlike monocyte-derived M2-like Mphi,
      HO-1 expression was defective in the majority of glomerular M2-like Mphi of
      patients with LN. Stimulation of human M2-like Mphi with type I interferons led
      to reduced HO-1 expression and increased Bach1 and IL-6 expression. Bach1
      deficient MRL/lpr mice exhibited increased HO-1 expression in kidneys, prolonged
      survival, reduced urine proteins, and serum blood urea nitrogen levels, but serum
      anti-dsDNA antibody levels were comparable. Increased expression of CD163 and HO
      1 was found in peritoneal Mphi from Bach1-deficient MRL/lpr mice. CONCLUSIONS:
      Our data suggest that dysregulated M2-like Mphi play a proinflammatory role in
      LN. Bach1 is a potential therapeutic target that could restore the anti
      inflammatory property of M2 Mphi.

PMID- 29636092
TI  - Self-medication practice and associated factors among adult household members in
      Meket district, Northeast Ethiopia, 2017.
AB  - BACKGROUND: Self-medication practice (SMP) is the use of medication without the
      prescription of health care professionals. The major problems associated with
      self-medication practice have been drug resistance, drug side effects, wastage of
      resources, and serious health hazards including death. Thus, the main purpose of
      this study was to assess the prevalence of self-medication practice and its
      associated factors among adult household members in Meket District, Northeast
      Ethiopia. METHODS: A community based cross-sectional study was conducted among
      722 adult household members in Meket District, from April 5 to May 5, 2017. The
      systematic random sampling method was used to select study participants. A pre
      tested, structured questionnaire was used for data collection using an
      interviewer-administered technique. Epi-info version and SPSS version 22 were
      utilized for data entry and analysis, respectively. Univariate and multivariate
      logistic regression was used to identify association factors. RESULTS: The
      overall prevalence of self-medication was found to be 35.9%. Unmarried status
      (AOR = 2.17, 95% CI = 1.18, 4.01), previous experience of self-medication (AOR =
      1.78, 95% CI = 1.22, 2.61), accessibility of pharmacies (AOR = 3.71, 95% CI =
      1.31, 10.51), peer/family pressure (AOR = 2.88, 95% CI = 1.98, 4.18) and presence
      of medication at home (AOR = 1.80, 95% CI = 1.11, 2.92) were factors associated
      with self-medication practices. CONCLUSION: More than one-third of the study
      participants practiced self-medication. Thus, strengthening communities awareness
      on drug side effects and integrated efforts of individuals, communities, health
      facilities, and regulatory bodies are highly necessary.

PMID- 29636093
TI  - Counting the dead to determine the source and transmission of the marine
      herpesvirus OsHV-1 in Crassostrea gigas.
AB  - Marine herpesviruses are responsible for epizootics in economically, ecologically
      and culturally significant taxa. The recent emergence of microvariants of Ostreid
      herpesvirus 1 (OsHV-1) in Pacific oysters Crassostrea gigas has resulted in
      socioeconomic losses in Europe, New Zealand and Australia however, there is no
      information on their origin or mode of transmission. These factors need to be
      understood because they influence the way the disease may be prevented and
      controlled. Mortality data obtained from experimental populations of C. gigas
      during natural epizootics of OsHV-1 disease in Australia were analysed
      qualitatively. In addition we compared actual mortality data with those from a
      Reed-Frost model of direct transmission and analysed incubation periods using
      Sartwell's method to test for the type of epizootic, point source or propagating.
      We concluded that outbreaks were initiated from an unknown environmental source
      which is unlikely to be farmed oysters in the same estuary. While direct oyster
      to-oyster transmission may occur in larger oysters if they are in close proximity
      (< 40 cm), it did not explain the observed epizootics, point source exposure and
      indirect transmission being more common and important. A conceptual model is
      proposed for OsHV-1 index case source and transmission, leading to endemicity
      with recurrent seasonal outbreaks. The findings suggest that prevention and
      control of OsHV-1 in C. gigas will require multiple interventions. OsHV-1 in C.
      gigas, which is a sedentary animal once beyond the larval stage, is an
      informative model when considering marine host-herpesvirus relationships.

PMID- 29636094
TI  - Fast acquisition of a polysaccharide fermenting gut microbiome by juvenile green
      turtles Chelonia mydas after settlement in coastal habitats.
AB  - BACKGROUND: Tetrapods do not express hydrolases for cellulose and hemicellulose
      assimilation, and hence, the independent acquisition of herbivory required the
      establishment of new endosymbiotic relationships between tetrapods and microbes.
      Green turtles (Chelonia mydas) are one of the three groups of marine tetrapods
      with an herbivorous diet and which acquire it after several years consuming
      pelagic animals. We characterized the microbiota present in the feces and rectum
      of 24 young wild and captive green turtles from the coastal waters of Brazil,
      with curved carapace length ranging from 31.1 to 64.7 cm, to test the hypotheses
      that (1) the ontogenetic dietary shift after settlement is followed by a gradual
      change in the composition and diversity of the gut microbiome, (2) differences
      exist between the composition and diversity of the gut microbiome of green
      turtles from tropical and subtropical regions, and (3) the consumption of
      omnivorous diets modifies the gut microbiota of green turtles. RESULTS: A genomic
      library of 2,186,596 valid bacterial 16S rRNA reads was obtained and these
      sequences were grouped into 6321 different operational taxonomic units (at 97%
      sequence homology cutoff). The results indicated that most of the juvenile green
      turtles less than 45 cm of curved carapace length exhibited a fecal microbiota co
      dominated by representatives of the phyla Bacteroidetes and Firmicutes and high
      levels of Clostridiaceae, Prophyromonas, Ruminococaceae, and Lachnospiraceae
      within the latter phylum. Furthermore, this was the only microbiota profile found
      in wild green turtles > 45 cm CCL and in most of the captive green turtles of any
      size feeding on a macroalgae/fish mixed diet. Nevertheless, microbial diversity
      increased with turtle size and was higher in turtles from tropical than from
      subtropical regions. CONCLUSIONS: These results indicate that juvenile green
      turtles from the coastal waters of Brazil had the same general microbiota,
      regardless of body size and origin, and suggest a fast acquisition of a
      polysaccharide fermenting gut microbiota by juvenile green turtles after
      settlement into coastal habitats.

PMID- 29636095
TI  - Osteoclasts degrade bone and cartilage knee joint compartments through different
      resorption processes.
AB  - BACKGROUND: Osteoclasts have been strongly implicated in osteoarthritic cartilage
      degradation, at least indirectly via bone resorption, and have been shown to
      degrade cartilage in vitro. The osteoclast resorption processes required to
      degrade subchondral bone and cartilage-the remodeling of which is important in
      the osteoarthritic disease process-have not been previously described, although
      cathepsin K has been indicated to participate. In this study we profile
      osteoclast-mediated degradation of bovine knee joint compartments in a novel in
      vitro model using biomarkers of extracellular matrix (ECM) degradation to assess
      the potential of osteoclast-derived resorption processes to degrade different
      knee joint compartments. METHODS: Mature human osteoclasts were cultured on ECMs
      isolated from bovine knees-articular cartilage, cortical bone, and osteochondral
      junction ECM (a subchondral bone-calcified cartilage mixture)-in the presence of
      inhibitors: the cystein protease inhibitor E-64, the matrix metalloproteinase
      (MMP) inhibitor GM6001, or the vacuolar-type H+-ATPase (V-ATPase) inhibitor
      diphyllin. Biomarkers of bone (calcium and C-terminal type I collagen (CTX-I))
      and cartilage (C2M) degradation were measured in the culture supernatants.
      Cultures without osteoclasts were used as background samples. Background
      subtracted biomarker levels were normalized to the vehicle condition and were
      analyzed using analysis of variance with Tukey or Dunnett's T3 post hoc test, as
      applicable. RESULTS: Osteochondral CTX-I release was inhibited by E-64 (19% of
      vehicle, p = 0.0008), GM6001 (51% of vehicle, p = 0.013), and E-64/GM6001
      combined (4% of vehicle, p = 0.0007)-similarly to bone CTX-I release. Diphyllin
      also inhibited osteochondral CTX-I release (48% of vehicle, p = 0.014), albeit
      less than on bone (4% of vehicle, p < 0.0001). Osteochondral C2M release was only
      inhibited by E-64 (49% of vehicle, p = 0.07) and GM6001 (14% of vehicle, p =
      0.006), with complete abrogation when combined (0% of vehicle, p = 0.004).
      Cartilage C2M release was non-significantly inhibited by E-64 (69% of vehicle, p
      = 0.98) and was completely abrogated by GM6001 (0% of vehicle, p = 0.16).
      CONCLUSIONS: Our study supports that osteoclasts can resorb non-calcified and
      calcified cartilage independently of acidification. We demonstrated both MMP
      mediated and cysteine protease-mediated resorption of calcified cartilage.
      Osteoclast functionality was highly dependent on the resorbed substrate, as
      different ECMs required different osteoclast processes for degradation. Our novel
      culture system has potential to facilitate drug and biomarker development aimed
      at rheumatic diseases, e.g. osteoarthritis, where pathological osteoclast
      processes in specific joint compartments may contribute to the disease process.

PMID- 29636096
TI  - The development of large-scale de-identified biomedical databases in the age of
      genomics-principles and challenges.
AB  - Contemporary biomedical databases include a wide range of information types from
      various observational and instrumental sources. Among the most important features
      that unite biomedical databases across the field are high volume of information
      and high potential to cause damage through data corruption, loss of performance,
      and loss of patient privacy. Thus, issues of data governance and privacy
      protection are essential for the construction of data depositories for biomedical
      research and healthcare. In this paper, we discuss various challenges of data
      governance in the context of population genome projects. The various challenges
      along with best practices and current research efforts are discussed through the
      steps of data collection, storage, sharing, analysis, and knowledge
      dissemination.

PMID- 29636098
TI  - Recent advances in plant and animal genomics are taking agriculture to new
      heights.
AB  - A report on the International Plant and Animal Genomes (PAG) conference held in
      San Diego, USA, 13-17 January 2018.

PMID- 29636097
TI  - Detection and genotyping of Trypanosoma cruzi from acai products commercialized
      in Rio de Janeiro and Para, Brazil.
AB  - BACKGROUND: Several cases of food-borne acute Chagas disease (ACD) have been
      reported in the Brazilian Amazon so far. Up to 2004, the occurrence of ACD by
      oral transmission, associated with food consumption, was rare. Recent cases of
      ACD in Brazil have been attributed to the consumption of juice from the acai palm
      containing reservoir animals or insect vectors waste, infected with Trypanosoma
      cruzi. This study aimed to determine the T. cruzi contamination rate and to
      genotype the parasite in food samples prepared from acai, which are
      commercialized in Rio de Janeiro and the Para States in Brazil. METHODS: The
      amplificability of DNA extracted from acai samples, and T. cruzi and Triatominae
      detection were performed by conventional PCR. Molecular characterization was done
      by multilocus PCR analysis, to determine the parasite discrete type units (DTUs)
      based on the size of PCR products in agarose gels, using the intergenic region of
      the spliced leader (SL), 24 Salpha rDNA and nuclear fragment A10 as targets.
      RESULTS: From the 140 samples of acai-based products analyzed, T. cruzi DNA was
      detected in 14 samples (10%); triatomine DNA was detected in one of these 14
      samples. The parasite genotyping demonstrated that food samples containing acai
      showed a mixture of T. cruzi DTUs with TcIII, TcV and TcI prevailing.
      CONCLUSIONS: In this study, the molecular detection and identification of T.
      cruzi from acai-based manufactured food samples, was performed for the first
      time. Although parasite DNA is a marker of possible contamination during food
      manufacturing, our findings do not indicate that acai is a source of Chagas
      disease via oral transmission per se, as live parasites were not investigated.
      Nevertheless, a molecular approach could be a powerful tool in the
      epidemiological investigation of outbreaks, supporting previous evidence that
      acai-based food can be contaminated with T. cruzi. Furthermore, both food quality
      control and assessment of good manufacturing practices involving acai-based
      products can be improved, assuring the safety of acai products.

PMID- 29636099
TI  - Correction to: Dual RNA-seq reveals viral infections in asthmatic children
      without respiratory illness which are associated with changes in the airway
      transcriptome.
AB  - In our recent article [1], it has come to our attention that the sample labels
      are not consistent between Table 1, the data labels deposited in the Sequence
      Read Archive, and Additional file 1: Table S2. We are therefore providing an
      updated Additional file 1: Table S2 so identical samples now have the same label.

PMID- 29636100
TI  - Tuberculous tenosynovitis of the flexor tendons of the wrist: a case report.
AB  - BACKGROUND: Tuberculous tenosynovitis poses a significant public health
      challenge, especially in developing countries. It usually affects the flexor
      tendons of the wrist. CASE PRESENTATION: We present a case of a 65-year-old
      Ghanaian female. She presented a progressively enlarging mass over the volar
      aspect of the right wrist and palm. She did not have a previous history of
      tuberculosis. However, her erythrocyte sedimentation rate was high and Mantoux
      (purified protein derivative) test was strongly positive (more than 15 mm).
      Radiograph of ulna, radius, and wrist showed osteopenic changes around the distal
      radius. Excision biopsy of the mass was done and samples sent for histopathology
      comment. The findings were an inflamed, thickened synovia with rice bodies:
      suggestive of tuberculous tenosynovitis. Anti-tuberculous chemotherapy was
      commenced on the second postoperative day. CONCLUSION: Tuberculous tenosynovitis
      of the wrist is uncommon. However, in developing countries like Ghana where
      tuberculosis is prevalent, it should be part of the differential diagnosis of
      compound palmar ganglion in order to prevent delayed diagnosis and treatment.

PMID- 29636101
TI  - Arteriovenous malformation in the sigmoid colon of a patient with Cowden disease
      treated with laparoscopy: a case report.
AB  - BACKGROUND: Cowden disease is a genetic disorder associated with a mutation of
      the PTEN gene and is known to be easily complicated by generalized vascular
      malformations and malignant tumors. However, only a few reports have investigated
      the relationship between Cowden disease and vascular malformations. We present a
      case of Cowden disease along with a review of the literature. CASE PRESENTATION:
      The patient was a 48-year-old man who visited our hospital complaining of fresh
      blood in his stools and shortness of breath. Hematological tests showed the
      patient had severe anemia. On physical examination, white papules-several
      millimeters in size-were observed between the patient's eyebrows. White papules
      were also observed on the left corner of his mouth and buccal mucosa. An upper
      gastrointestinal endoscopy showed densely-packed, white, flat protrusions in the
      esophagus. While lower gastrointestinal endoscopy revealed a mass accompanied by
      arterial pulsation in the sigmoid colon. A diagnosis of Cowden disease was
      confirmed and a laparoscopic sigmoidectomy was performed to address the
      arteriovenous malformations in the sigmoid colon. Post-surgery, the patient had
      an unremarkable recovery and was discharged 7 days later. CONCLUSIONS: We present
      a very rare case of Cowden disease with arteriovenous malformations occurring in
      the colon. Surgical resection is believed to be the first choice for treating
      congenital arteriovenous malformations of the intestines. However, the
      arteriovenous malformations in the colon in our patient were treated under
      laparoscopic guidance, making ours the first report describing laparoscopic
      treatment of colonic arteriovenous malformations occurring in the inferior
      mesenteric artery. Thus we demonstrate that laparoscopic treatment of
      arteriovenous malformations in the intestines is a minimally invasive and can be
      successfully applied in such cases.

PMID- 29636102
TI  - Forensic psychiatry, one subspecialty with two ethics? A systematic review.
AB  - BACKGROUND: Forensic psychiatry is a particular subspecialty within psychiatry,
      dedicated in applying psychiatric knowledge and psychiatric training for
      particular legal purposes. Given that within the scope of forensic psychiatry, a
      third party usually intervenes in the patient-doctor relationship, an amendment
      of the traditional ethical principles seems justified. RESULTS: Thus, 47
      articles, two book chapters and the guidelines produced by the World Psychiatric
      Association, the American Association of Psychiatry and the Law, as well as by
      the Royal Australian and New Zealand College of psychiatrists, were analyzed. The
      review revealed that the ethics of correctional forensic psychiatry and those of
      legal forensic psychiatry do not markedly differ from each other, but they are
      incongruent in terms of implementation. METHODS: In an effort to better
      understand which ethical principles apply to forensic psychiatry, a chronological
      review of the literature published from 1950 to 2015 was carried out. CONCLUSION:
      The ethics of correctional forensic psychiatry are primarily deontological. The
      principle of justice translates into the principle of health care equivalence,
      the principle of beneficence into providing the best possible care to patients,
      and the principle of respect of autonomy into ensuring confidentiality and
      informed consent. The ethics of legal forensic psychiatry are rather
      consequentialist. In this latter setting, the principle of justice is mainly
      characterized by professionalism, the principle of beneficence by objectivity and
      impartiality, and the principle of respect of autonomy by informed consent.
      However, these two distinct fields of forensic psychiatry share in common the
      principle of non maleficence, defined as the non collaboration of the
      psychiatrist in any activity leading to inhuman and degrading treatment or to the
      death penalty.

PMID- 29636103
TI  - Role of lymph node dissection in the management of upper tract urothelial
      carcinomas: a meta-analysis.
AB  - BACKGROUND: Lymph node dissection (LND) is not routinely performed during radical
      nephroureterectomy (RNU) in upper tract urothelial carcinomas (UTUC) and the role
      of LND has been controversial. We aim to investigate whether patients with LND
      had improved survival in UTUC patients. METHODS: We performed a systematic
      literature search of PubMed, Embase, and Cochrane library for citations published
      prior to January 2016, describing LND performed among UTUC patients and conducted
      a standard meta-analysis of survival outcomes. RESULTS: Eleven eligible studies
      containing 7516 patients satisfied the inclusion criteria. Pooled HRs for cancer
      specific survival (CSS) and recurrence-free survival (RFS) were 1.17 (P = 0.18)
      and 1.33 (P = 0.19) respectively. However, the patients in the LND group had more
      advanced tumour stages and grades (P < 0.001). Further subgroup analysis showed
      that among muscle-invasive UTUC patients, the pooled HR for CSS and RFS were 1.10
      (P = 0.42) and 0.92 (P = 0.72) respectively. Besides, no difference was found in
      CSS and RFS between pN0 and pNx individuals in overall populations and in
      patients with muscle-invasive UTUC, while pN+ patients had significantly worse
      prognosis when compared to pN0 patients. CONCLUSIONS: LND during RNU allows more
      accurate staging and prediction of survival, but it remains uncertain whether LND
      independently improves survival in patients with UTUC. However, standard use of
      LND should be further investigated in a multi-center, prospective evaluation to
      obtain a definitive statement regarding this matter.

PMID- 29636104
TI  - Antidiabetic treatment patterns and specialty care utilization among patients
      with type 2 diabetes and cardiovascular disease.
AB  - BACKGROUND: To evaluate real-world patient characteristics, medication use, and
      health care utilization patterns in patients with type 2 diabetes with
      established cardiovascular disease (CVD). METHODS: Cross-sectional analysis of
      patients with type 2 diabetes seen at Cleveland Clinic from 2005 to 2016, divided
      into two cohorts: with-CVD and without-CVD. Patient demographics and antidiabetic
      medications were recorded in December 2016; department encounters included all
      visits from 1/1/2016 to 12/31/2016. Comorbidity burden was assessed by the
      diabetes complications severity index (DCSI) score. RESULTS: Of 95,569 patients
      with type 2 diabetes, 40,910 (42.8%) were identified as having established CVD.
      Patients with CVD vs. those without were older (median age 69.1 vs. 58.2 years),
      predominantly male (53.8% vs. 42.6%), and more likely to have Medicare insurance
      (69.4% vs. 35.3%). The with-CVD cohort had a higher proportion of patients with a
      DCSI score >= 3 than the without-CVD cohort (65.0% vs. 10.3%). Utilization rates
      of glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter-2
      inhibitors were low in both with-CVD (4.1 and 2.5%) and without-CVD cohorts (5.4
      and 4.1%), respectively. The majority of patient visits (75%) were seen by a
      primary care provider. During the 1-year observation period, 81.9 and 62.0% of
      patients with type 2 diabetes and CVD were not seen by endocrinology or
      cardiology, respectively. CONCLUSIONS: These data indicated underutilization of
      specialists and antidiabetic medications reported to confer CV benefit in
      patients with type 2 diabetes and CVD. The impact of recently updated guidelines
      and cardiovascular outcome trial results on management patterns in such patients
      remains to be seen.

PMID- 29636105
TI  - The feasibility and positive effects of a customised videogame rehabilitation
      programme for freezing of gait and falls in Parkinson's disease patients: a pilot
      study.
AB  - BACKGROUND: Freezing of gait and falls represent a major burden in patients with
      advanced forms of Parkinson's disease (PD). These axial motor signs are not fully
      alleviated by drug treatment or deep-brain stimulation. Recently, virtual reality
      has emerged as a rehabilitation option for these patients. In this pilot study,
      we aim to determine the feasibility and acceptability of rehabilitation with a
      customised videogame to treat gait and balance disorders in PD patients, and
      assess its effects on these disabling motor signs. METHODS: We developed a
      customised videogame displayed on a screen using the Kinect system. To play, the
      patient had to perform large amplitude and fast movements of all four limbs,
      pelvis and trunk, in response to visual and auditory cueing, to displace an
      avatar to collect coins and avoid obstacles to gain points. We tested ten
      patients with advanced forms of PD (median disease duration = 16.5 years)
      suffering from freezing of gait and/or falls (Hoehn&Yahr score >= 3) resistant to
      antiparkinsonian treatment and deep brain stimulation. Patients performed 18
      training sessions during a 6-9 week period. We measured the feasibility and
      acceptability of our rehabilitation programme and its effects on parkinsonian
      disability, gait and balance disorders (with clinical scales and kinematics
      recordings), positive and negative affects, and quality of life, after the 9th
      and 18th training sessions and 3 months later. RESULTS: All patients completed
      the 18 training sessions with high feasibility, acceptability and satisfaction
      scores. After training, the freezing-of-gait questionnaire, gait-and-balance
      scale and axial score significantly decreased by 39, 38 and 41%, respectively,
      and the activity-balance confidence scale increased by 35%. Kinematic gait
      parameters also significantly improved with increased step length and gait
      velocity and decreased double-stance time. Three months after the final session,
      no significant change persisted except decreased axial score and increased step
      length and velocity. CONCLUSIONS: This study suggests that rehabilitation with a
      customised videogame to treat gait and balance disorders is feasible, well
      accepted, and effective in parkinsonian patients. These data serve as preliminary
      evidence for further larger and controlled studies to propose this customised
      videogame rehabilitation programme at home. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT02469350 .

PMID- 29636106
TI  - Predictors of switch to and early outcomes on third-line antiretroviral therapy
      at a large public-sector clinic in Johannesburg, South Africa.
AB  - BACKGROUND: While efficacy data exist, there are limited data on the outcomes of
      patients on third-line antiretroviral therapy (ART) in sub-Saharan Africa in
      actual practice. Being able to identify predictors of switch to third-line ART
      will be essential for planning for future need. We identify predictors of switch
      to third-line ART among patients with significant viraemia on a protease
      inhibitor (PI)-based second-line ART regimen. Additionally, we describe
      characteristics of all patients on third-line at a large public sector HIV clinic
      and present their early outcomes. METHODS: Retrospective analysis of adults (>=
      18 years) on a PI-based second-line ART regimen at Themba Lethu Clinic,
      Johannesburg, South Africa as of 01 August 2012, when third-line treatment became
      available in South Africa, with significant viraemia on second-line ART (defined
      as at least one viral load >= 1000 copies/mL on second-line ART after 01 August
      2012) to identify predictors of switch to third-line (determined by genotype
      resistance testing). Third-line ART was defined as a regimen containing
      etravirine, raltegravir or ritonavir boosted darunavir, between August 2012 and
      January 2016. To assess predictors of switch to third-line ART we used Cox
      proportional hazards regression among those with significant viraemia on second
      line ART after 01 August 2012. Then among all patients on third-line ART we
      describe viral load suppression, defined as a viral load < 400 copies/mL, after
      starting third-line ART. RESULTS: Among 719 patients in care and on second-line
      ART as of August 2012 (with at least one viral load >= 1000 copies/mL after 01
      August 2012), 36 (5.0% over a median time of 54 months) switched to third-line.
      Time on second-line therapy (>= 96 vs. < 96 weeks) (adjusted Hazard Ratio (aHR):
      2.53 95% CI 1.03-6.22) and never reaching virologic suppression while on second
      line ART (aHR: 3.37 95% CI 1.47-7.73) were identified as predictors of switch. In
      a separate cohort of patients on third-line ART, 78.3% (47/60) and 83.3% (35/42)
      of those in care and with a viral load suppressed their viral load at 6 and 12
      months, respectively. CONCLUSIONS: Our results show that the need for third-line
      is low (5%), but that patients' who switch to third-line ART have good early
      treatment outcomes and are able to suppress their viral load. Adherence
      counselling and resistance testing should be prioritized for patients that are at
      risk of failure, in particular those who never suppress on second-line and those
      who have been on PI-based regimen for extended periods.

PMID- 29636108
TI  - GDF15 promotes the proliferation of cervical cancer cells by phosphorylating AKT1
      and Erk1/2 through the receptor ErbB2.
AB  - BACKGROUND: Growth differentiation factor 15 (GDF15) is a member of the TGF-beta
      superfamily, and evidence suggests that a substantial amount of GDF15 is secreted
      in various human cancers, such as ovarian cancer, prostate cancer, and breast
      cancer, among others. However, the function of GDF15 in cervical cancer has not
      yet been reported. METHODS: Immunohistochemistry was used to detect GDF15
      expression in normal cervix and in different cervical cancer lesions. Cell growth
      curves, MTT, tumor formation assays and flow cytometry were utilized to observe
      the effects of ectopic GDF15 expression on the proliferation and cell cycle of
      cervical cancer cells. Real-time PCR, western blotting and immunoprecipitation
      assays were conducted to measure the expression of genes related to the cell
      cycle and the PI3K/AKT and MAPK/ERK signaling pathways. A chromatin
      immunoprecipitation assay was performed to confirm whether C-myc bound to a
      specific region of the GDF15 promoter. Inhibitor treatment and
      immunoprecipitation assays were employed to identify the association between
      GDF15 and ErbB2. RESULTS: GDF15 expression gradually increased during the
      progression of cervical carcinogenesis. GDF15 promoted cervical cancer cell
      proliferation via exogenous rhGDF15 treatment or the use of gene editing
      technology in vitro and in vivo and significantly accelerated the cell cycle
      transition from G0/G1 to S phase. The expression of p-ErbB2, p-AKT1, p-Erk1/2,
      CyclinD1 and CyclinE1 was up-regulated and the expression of p21 was down
      regulated in GDF15-overexpressing and rhGDF15-treated cervical cancer cells. C
      myc trans-activated GDF15 expression by binding to the E-box motifs in the
      promoter of GDF15 and contributed to the positive feedback of GDF15/C-myc/GDF15.
      Furthermore, GDF15 bound to ErbB2 in a protein complex in cervical cancer cells.
      CONCLUSIONS: Our data demonstrated that GDF15 promoted the proliferation of
      cervical cancer cells via the up-regulation of CyclinD1 and CyclinE1 and the down
      regulation of p21 through both the PI3K/AKT and MAPK/ERK signaling pathways in a
      complex with ErbB2.

PMID- 29636107
TI  - Epidermal necrolysis French national diagnosis and care protocol (PNDS; protocole
      national de diagnostic et de soins).
AB  - Epidermal necrolysis (EN) encompasses Stevens-Johnson syndrome (SJS, < 10% of the
      skin affected), Lyell syndrome (toxic epidermal necrolysis, TEN, with >=30% of
      the skin affected) and an overlap syndrome (10 to 29% of the skin affected).
      These rare diseases are caused, in 85% of cases, by pharmacological treatments,
      with symptoms occurring 4 to 28 days after treatment initiation. Mortality is 20
      to 25% during the acute phase, and almost all patients display disabling sequelae
      (mostly ocular impairment and psychological distress).The objective of this
      French national diagnosis and care protocol (protocole national de diagnostic et
      de soins; PNDS), based on a critical literature review and on a multidisciplinary
      expert consensus, is to provide health professionals with an explanation of the
      optimal management and care of patients with EN. This PNDS, written by the French
      National Reference Center for Toxic Bullous Dermatoses was updated in 2017 (
      https://www.has-sante.fr/portail/jcms/c_1012735/fr/necrolyse-epidermique
      syndromes-de-stevens-johnson-et-de-lyell ). The cornerstone of the management of
      these patients during the acute phase is an immediate withdrawal of the
      responsible drug, patient management in a dermatology department, intensive care
      or burn units used to dealing with this disease, supportive care and close
      monitoring, the prevention and treatment of infections, and a multidisciplinary
      approach to sequelae. Based on published data, it is not currently possible to
      recommend any specific immunomodulatory treatment. Only the culprit drug and
      chemically similar molecules must be lifelong contraindicated.

PMID- 29636109
TI  - Failure of remission induction by glucocorticoids alone or in combination with
      immunosuppressive agents in IgG4-related disease: a prospective study of 215
      patients.
AB  - BACKGROUND: The aim of this study was to assess the outcomes of remission
      induction in patients with IgG4-related disease (IgG4-RD) in our cohort, and to
      investigate the characteristics, prognosis, and risk factors in the patients
      failed of remission induction. METHODS: We prospectively enrolled 215 newly
      diagnosed patients with IgG4-RD, who were initially treated with glucocorticoid
      (GC) alone or in combination with immunosuppressive agents (IM), and had at least
      6 months of follow up. The therapeutic goals of remission induction were defined
      as fulfilling each of the following after the 6-month remission induction stage:
      (1) >= 50% decline in the IgG4-RD responder index (RI); (2) GC tapered to
      maintenance dose; and (3) no relapse during GC tapering. The patients not
      achieving the therapeutic goals were considered to have failed of remission
      induction. RESULTS: There were 26 patients in our cohort who failed of remission
      induction, including 16 (20.8%) on GC monotherapy, and 10 (7.2%) on combination
      therapy comprising GC and IM. The lacrimal gland and lung were most common sites
      of remission induction failure. Among the patients who relapsed during remission
      induction stage, 52.9% had secondary relapse during follow-up. Eosinophilia,
      higher baseline RI, more than five organs involved and dacryoadenitis were risk
      factors for remission induction failure with GC monotherapy, and the incidence of
      remission induction failure was 71.4% in the patients with more than three risk
      factors. After 6-month treatment, the patients who failed of remission induction
      had significantly higher erythrocyte sedimentation rate (ESR), C-reactive protein
      (CRP) and IgG4. CONCLUSION: In our cohort, 20.8% of patients failed of remission
      induction with GC monotherapy, while 7.2% of patients failed of remission
      induction with combination therapy comprising GC and IM.

PMID- 29636110
TI  - Matrix metalloproteinase-9 (MMP9) is involved in the TNF-alpha-induced fusion of
      human M13SV1-Cre breast epithelial cells and human MDA-MB-435-pFDR1 cancer cells.
AB  - BACKGROUND: In addition to physiological events such as fertilisation,
      placentation, osteoclastogenesis, or tissue regeneration/wound healing, cell
      fusion is involved in pathophysiological conditions such as cancer. Cell fusion,
      which applies to both the proteins and conditions that induce the merging of two
      or more cells, is not a fully understood process. Inflammation/pro-inflammatory
      cytokines might be a positive trigger for cell fusion. Using a Cre-LoxP-based
      cell fusion assay we demonstrated that the fusion between human M13SV1-Cre breast
      epithelial cells and human MDA-MB-435-pFDR1 cancer cells was induced by the pro
      inflammatory cytokine tumour necrosis factor-alpha (TNF-alpha). METHODS: The gene
      expression profile of the cells in the presence of TNF-alpha and under normoxic
      and hypoxic conditions was analysed by cDNA microarray analysis. cDNA microarray
      data were verified by qPCR, PCR, Western blot and zymography. Quantification of
      cell fusion events was determined by flow cytometry. Proteins of interest were
      either blocked or knocked-down using a specific inhibitor, siRNA or a blocking
      antibody. RESULTS: The data showed an up-regulation of various genes, including
      claudin-1 (CLDN1), ICAM1, CCL2 and MMP9 in M13SV1-Cre and/or MDA-MB-435-pFDR1
      cells. Inhibition of these proteins using a blocking ICAM1 antibody, CLDN1 siRNA
      or an MMP9 inhibitor showed that only the blockage of MMP9 was correlated with a
      decreased fusion rate of the cells. Likewise, the tetracycline-based antibiotic
      minocycline, which exhibits anti-inflammatory properties, was also effective in
      both inhibiting the TNF-alpha-induced MMP9 expression in M13SV1-Cre cells and
      blocking the TNF-alpha-induced fusion frequency of human M13SV1-Cre breast
      epithelial cells and human MDA-MB-435-pFDR1 cancer cells. CONCLUSIONS: The matrix
      metalloproteinase-9 (MMP9) is most likely involved in the TNF-alpha-mediated
      fusion of human M13SV1-Cre breast epithelial cells and human MDA-MB-435-pFDR1
      cancer cells. Likewise, our data indicate that the tetracycline-based antibiotic
      minocycline might exhibit anti-fusogenic properties because it inhibits a cell
      fusion-related mechanism.

PMID- 29636111
TI  - Anti-CCP antibodies and bone.

PMID- 29636112
TI  - A simple management option for chronically impacted sharp tracheobronchial
      foreign bodies in children.
AB  - Distally impacted chronic tracheobronchial sharp foreign bodies in children are a
      management challenge that presents with clinical subtlety and extreme
      variability. The use of image guided techniques, imaginative instrumentation,
      tracheotomy, thoracotomy, and even extracorporeal membrane oxygneation have been
      reported. Endoscopy is made difficult by the distal location, inflammatory
      reaction with granulation tissue formation, and bleeding obscuring the foreign
      body. Our aim is to describe our experience with two children who had removal of
      aspirated impacted sharp metallic foreign bodies from the distal airway using
      rigid bronchoscopy, preceded by maximal medical therapy.

PMID- 29636113
TI  - Seasonal abundance, blood meal sources and insecticide susceptibility in major
      anopheline malaria vectors from southern Mauritania.

PMID- 29636115
TI  - A unique epigenomic landscape defines the characteristics and differentiation
      potentials of glioma stem cells.
AB  - A new study reveals comprehensive and unique epigenetic properties of glioma stem
      cells, leading to novel molecular insights and therapeutic potentials toward
      glioblastoma multiforme treatment.

PMID- 29636116
TI  - Use of vaccines and factors associated with their uptake variability in dogs,
      cats and rabbits attending a large sentinel network of veterinary practices
      across Great Britain.
AB  - Vaccination remains a mainstay of companion animal population health. However,
      how vaccine use at a population level complies with existing guidelines is
      unknown. Here we use electronic health records to describe vaccination in dogs,
      cats and rabbits attending a large sentinel network of UK veterinary practices.
      In total, 77.9% (95% CI: 77.6-78.1) of animals had recorded vaccinations. The
      percentage of animals with recorded vaccinations was higher in dogs, neutered
      animals, in insured dogs and cats and in purebred dogs. Vaccination rates varied
      in different regions of Great Britain in all species. Dogs and cats belonging to
      owners living in less deprived areas of England and Scotland were more likely to
      be recorded as vaccinated. In the vaccinated population, cats received more core
      vaccines per year of life (0.86) than dogs (0.75), with feline leukaemia vaccines
      almost as frequent as core vaccines. In dogs, leptospira vaccines were more
      frequent than core vaccines. This descriptive study suggests a substantial
      proportion of animals are not benefiting from vaccine protection. For the first
      time, we identify potential factors associated with variations in recorded
      vaccination frequency, providing a critical baseline against which to monitor
      future changes in companion animal vaccination and evidence to inform future
      targeted health interventions.

PMID- 29636114
TI  - Allopregnanolone alters follicular and luteal dynamics during the estrous cycle.
AB  - BACKGROUND: Allopregnanolone is a neurosteroid synthesized in the central nervous
      system independently of steroidogenic glands; it influences sexual behavior and
      anxiety. The aim of this work is to evaluate the indirect effect of a single
      pharmacological dose of allopregnanolone on important processes related to normal
      ovarian function, such as folliculogenesis, angiogenesis and luteolysis, and to
      study the corresponding changes in endocrine profile and enzymatic activity over
      4 days of the rat estrous cycle. We test the hypothesis that allopregnanolone may
      trigger hypothalamus - hypophysis - ovarian axis dysregulation and cause ovarian
      failure which affects the next estrous cycle stages. METHODS: Allopregnanolone
      was injected during the proestrous morning and then, the animals were sacrificed
      at each stage of the estrous cycle. Ovarian sections were processed to determine
      the number and diameter of different ovarian structures. Cleaved caspase 3,
      proliferating cell nuclear antigen, alpha-actin and Von Willebrand factor
      expressions were evaluated by immunohistochemistry. Luteinizing hormone,
      prolactin, estrogen and progesterone serum levels were measured by
      radioimmunoassay. The enzymatic activities of 3beta-hydroxysteroid dehydrogenase,
      3alpha-hydroxysteroid oxidoreductase and 20alpha-hydroxysteroid dehydrogenase
      were determined by spectrophotometric assays. Two-way ANOVA followed by
      Bonferroni was performed to determine statistical differences between control and
      treated groups along the four stages of the cycle. RESULTS: The results indicate
      that allopregnanolone allopregnanolone decreased the number of developing
      follicles, while atretic follicles and cysts increased with no effects on normal
      cyclicity. Some cysts in treated ovaries showed morphological characteristics
      similar to luteinized unruptured follicles. The apoptosis/proliferation balance
      increased in follicles from treated rats. The endocrine profile was altered at
      different stages of the estrous cycle of treated rats. The angiogenic markers
      expression increased in treated ovaries. As regards corpora lutea, the
      apoptosis/proliferation balance and 20alpha-hydroxysteroid dehydrogenase
      enzymatic activity decreased significantly. Progesterone levels and 3beta
      hydroxysteroid dehydrogenase enzymatic activity increased in treated rats. These
      data suggest that allopregnanolone interferes with steroidogenesis and
      folliculogenesis at different stages of the cycle. CONCLUSION: Allopregnanolone
      interferes with corpora lutea regression, which might indicate that this
      neurosteroid exerts a protective role over the luteal cells and prevents them
      from luteolysis. Allopregnanolone plays an important role in the ovarian
      pathophysiology.

PMID- 29636117
TI  - Personalised treatments for traumatic brain injury: cognitive, emotional and
      motivational targets.

PMID- 29636118
TI  - Replacement of saturated and trans-fatty acids in the diet v. CVD risk in the
      light of the most recent studies.
AB  - OBJECTIVE: To present and discuss results of the most recent studies pertaining
      to the effects of consumption of different types of fatty acids on the risk of
      CVD. The aim was also an attempt to answer the question of whether a revision of
      the current recommendations is necessary. DESIGN: A review of prospective cohort
      studies, systematic reviews and meta-analyses published in 2014-2017 on the
      effects of SFA and trans-fatty acid (TFA) intakes as well as various models of
      their replacement in the diet on CVD risk. RESULTS: Results of the new large
      prospective cohort studies pertaining to the effect of SFA consumption on CVD
      risk are contradictory. Similarly, the recent meta-analyses of clinical trials
      related to the effects of SFA substitution on CVD risk provided extremely
      different results, which is related to the application of different inclusion and
      exclusion criteria. Differences in results of randomised controlled trials may be
      caused by different methodologies of dietary parameter changes, varying duration
      of studies, as well as the time at which they were carried out. CONCLUSIONS: It
      is extremely difficult to extrapolate results of recent studies to contemporary
      recommendations. It seems that there is a need for properly randomised studies on
      large groups, with good control of dietary and non-dietary parameters, which
      account for not only the sum of SFA and TFA, but also their source. Only such
      studies will allow for full evaluation of an effect of substituting SFA and TFA
      on cardiovascular risk.

PMID- 29636119
TI  - HIV and viral hepatitis coinfection analysis using surveillance data from 15 US
      states and two cities.
AB  - Coinfection with human immunodeficiency virus (HIV) and viral hepatitis is
      associated with high morbidity and mortality in the absence of clinical
      management, making identification of these cases crucial. We examined
      characteristics of HIV and viral hepatitis coinfections by using surveillance
      data from 15 US states and two cities. Each jurisdiction used an automated
      deterministic matching method to link surveillance data for persons with reported
      acute and chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections,
      to persons reported with HIV infection. Of the 504 398 persons living with
      diagnosed HIV infection at the end of 2014, 2.0% were coinfected with HBV and
      6.7% were coinfected with HCV. Of the 269 884 persons ever reported with HBV,
      5.2% were reported with HIV. Of the 1 093 050 persons ever reported with HCV,
      4.3% were reported with HIV. A greater proportion of persons coinfected with HIV
      and HBV were males and blacks/African Americans, compared with those with HIV
      monoinfection. Persons who inject drugs represented a greater proportion of those
      coinfected with HIV and HCV, compared with those with HIV monoinfection. Matching
      HIV and viral hepatitis surveillance data highlights epidemiological
      characteristics of persons coinfected and can be used to routinely monitor health
      status and guide state and national public health interventions.

PMID- 29636120
TI  - Long noncoding RNA: multiple players in gene expression.
AB  - Previously considered as a component of transcriptional noise, long noncoding
      RNAs (lncRNAs) were neglected as a therapeutic target, however, recently
      increasing evidence has shown that lncRNAs can participate in numerous biological
      processes involved in genetic regulation including epigenetic, transcriptional,
      and post-transcriptional regulation. In this review, we discuss the fundamental
      functions of lncRNAs at different regulatory levels and their roles in metabolic
      balance. Typical examples are introduced to illustrate their diverse molecular
      mechanisms. The comprehensive investigation and identification of key lncRNAs
      will not only contribute to insights into diseases, such as breast cancer and
      type II diabetes, but also provide promising therapeutic targets for related
      diseases. [BMB Reports 2018; 51(6): 280-289].

PMID- 29636121
TI  - Understanding of the functional role(s) of the Activating Transcription Factor
      4(ATF4) in HIV regulation and production.
AB  - The activating transcription factor (ATF) 4 belongs to the ATF/CREB (cAMP
      Response Element Binding bZIP [Basic Leucine Zipper]) transcription factor
      family, and plays a central role in the UPR (Unfolded Protein Response) process
      in cells. The induction of ATF4 expression has previously been shown to increase
      the replication of HIV-1. However, the detailed mechanism underlying this effect
      and the factors involved in the regulation of ATF4 function are still unknown.
      Here, we demonstrate first that knocking out ATF4 using siRNA shows a strong
      negative effect on HIV-1 production, indicating that ATF4 is a functional
      positive cellular factor in HIV-1 production. To determine the mechanism by which
      ATF4 regulates the HIV-1 life cycle, we assessed the effect of the overexpression
      of wild type ATF4 and its various derivatives on HIV-1 LTR-mediated
      transcriptional activation and the production of HIV-1 particles. This effect was
      studied through co-transfection experiments with either reporter vectors or
      proviral DNA. We found that the N-terminal domains of ATF4 are involved in HIV-1
      LTR-mediated transcriptional activation, and thus in HIV-1 production. [BMB
      Reports 2018; 51(8): 388-393].

PMID- 29636123
TI  - Welcome.

PMID- 29636122
TI  - The role of necroptosis in the treatment of diseases.
AB  - Necroptosis is an emerging form of programmed cell death occurring via active and
      well-regulated necrosis, distinct from apoptosis morphologically, and
      biochemically. Necroptosis is mainly unmasked when apoptosis is compromised in
      response to tumor necrosis factor alpha. Unlike apoptotic cells, which are
      cleared by macrophages or neighboring cells, necrotic cells release danger
      signals, triggering inflammation, and exacerbating tissue damage. Evidence
      increasingly suggests that programmed necrosis is not only associated with
      pathophysiology of disease, but also induces innate immune response to viral
      infection. Therefore, necroptotic cell death plays both physiological and
      pathological roles. Physiologically, necroptosis induce an innate immune response
      as well as premature assembly of viral particles in cells infected with virus
      that abrogates host apoptotic machinery. On the other hand, necroptosis per se is
      detrimental, causing various diseases such as sepsis, neurodegenerative diseases
      and ischemic reperfusion injury. This review discusses the signaling pathways
      leading to necroptosis, associated necroptotic proteins with target-specific
      inhibitors and diseases involved. Several studies currently focus on protective
      approaches to inhibiting necroptotic cell death. In cancer biology, however,
      anticancer drug resistance severely hampers the efficacy of chemotherapy based on
      apoptosis. Pharmacological switch of cell death finds therapeutic application in
      drug- resistant cancers. Therefore, the possible clinical role of necroptosis in
      cancer control will be discussed in brief. [BMB Reports 2018; 51(5): 219-224].

PMID- 29636124
TI  - In situ formation of injectable chitosan-gelatin hydrogels through double
      crosslinking for sustained intraocular drug delivery.
AB  - Rapid clearance and low ocular bioavailability are drawbacks of conventional
      ophthalmic eye drops. To increase the ocular drug resistance time and improve
      efficacy, an in situ forming and thermosensitive chitosan-gelatin hydrogel was
      developed. The feasibility of using this hydrogel as a topical eye drop
      formulation for sustained release of timolol maleate was evaluated. The flexible
      hydrogel that was co-crosslinked with beta-glycerophosphate disodium salt hydrate
      (beta-GD) and genipin showed a fast gel formation at 37  degrees C. The swelling
      properties and in vitro biodegradation characteristics showed a strong
      relationship with the initial genipin concentration. In vitro release profiles
      demonstrated that crosslinking with genipin reduced the release rate of entrapped
      model drugs and timolol maleate. In vitro cytotoxicity tests showed that the
      hydrogel was non-toxic to Chinese hamster fibroblast V79 cells. The hydrogel was
      further applied as eye drop formulations for sustained release of timolol maleate
      to reduce intraocular pressure (IOP). A fast gel formation was observed after
      instilling the chitosan-gelatin solution into the lower conjunctival sac of the
      rabbit eyes, and the in situ formed hydrogels protected the drugs from clearance
      by tears, and released the drugs in a sustained manner. Furthermore,
      administration of timolol maleate containing chitosan-gelatin hydrogels showed a
      long-lasting and effective IOP lowering efficacy for up to 24 h compared with the
      conventional eye drops. These results suggested that beta-GD and genipin co
      crosslinked chitosan-gelatin hydrogels could be a useful ocular drug delivery
      platform with enhanced therapeutic effects and reduced side effects.

PMID- 29636125
TI  - Elucidating molecular events underlying topography mediated cardiomyogenesis of
      stem cells on 3D nanofibrous scaffolds.
AB  - Toward engineering a cardiac patch, the objective of this work was to assess stem
      cell response to a three-dimensional (3D) nanofibrous scaffold and probe the
      underlying molecular mechanisms including both cell signaling and epigenetic
      changes. Cardiomyogenesis of human mesenchymal stem cells (hMSCs) in 3D
      poly(epsilon-caprolactone) (PCL) nanofibers and macroporous scaffolds was
      compared with two-dimensional (2D) PCL films. In addition, nanofiber mats of PCL
      and its blend with gelatin (PCL-Gel) were prepared with fibers of random or
      unidirectional alignment to assess the roles of topography (fibrous architecture
      and its alignment) and biochemical cue (cell-adhesive sites) in directing cell
      functions. Cells on 3D random nanofibers, exhibited elevated expression of known
      cardiac markers such as cardiac actinin, cardiac troponin and beta-myocardial
      heavy chain compared to cells on 2D films suggesting enhanced differentiation
      that was further accentuated on the aligned fibers. 3D macroporous scaffolds did
      not enhance the cardiomyogenic differentiation. However, minimal differences were
      noted between cells on PCL and PCL-Gel fibers, irrespective of alignment. Co
      culture with neonatal rat cardiomyocytes induced beating in the differentiated
      cells. The use of small molecule inhibitors revealed that cytoskeletal elements F
      actin, microtubules and downstream ROCK protein are essential for the
      cardiomyogenesis of hMSCs on the nanofibers. The activation of ERK, AKT and mTOR
      was observed during cardiomyogenesis. Interestingly, enhanced differentiation on
      the aligned nanofibers was associated with increased level of the histone
      deacytelase SIRT6 and decreased level of the acetylated histone H3K9 suggesting a
      role for epigenetic regulation. This study demonstrates that aligned nanofibrous
      scaffolds augment cardiomyogenic differentiation wherein topography plays a
      critical role in driving stem cell function. In addition, this study offers
      insight into molecular pathways driving the cellular response.

PMID- 29636126
TI  - Zinc and nitrogen ornamented bluish white luminescent carbon dots for engrossing
      bacteriostatic activity and Fenton based bio-sensor.
AB  - Carbon dots with heteroatom co-doping associated with consummate luminescence
      features are of acute interest in diverse applications such as biomolecule
      markers, chemical sensing, photovoltaic, and trace element detection. Herein, we
      demonstrate a straightforward, highly efficient hydrothermal dehydration
      technique to synthesize zinc and nitrogen co-doped multifunctional carbon dots
      (N, Zn-CDs) with superior quantum yield (50.8%). The luminescence property of the
      carbon dots can be tuned by regulating precursor ratio and surface oxidation
      states in the carbon dots. A unique attribution of the as-prepared carbon dots is
      the high monodispersity and robust excitation-independent emission behavior that
      is stable in enormously reactive environment and over a wide range of pH. These
      N, Zn-CDs unveils captivating bacteriostatic activity against gram-negative
      bacteria Escherichia coli. Furthermore, the excellent luminescence properties of
      these carbon dots were applied as a platform of sensitive biosensor for the
      detection of hydrogen peroxide. Under optimized conditions, these N, Zn-CDs
      reveals high sensitivity over a broad range of concentrations with an ultra-low
      limit of detection (LOD) indicating their pronounced prospective as a fluorescent
      probe for chemical sensing. Overall, the experimental outcomes propose that these
      zero-dimensional nano-dots could be developed as bacteriostatic agents to control
      and prevent the persistence and spreading of bacterial infections and as a
      fluorescent probe for hydrogen peroxide detection.

PMID- 29636127
TI  - Antioxidant and antibacterial hydroxyapatite-based biocomposite for orthopedic
      applications.
AB  - Post-implantation, vicinity acquired oxidative stress and bacterial infections
      lead to apoptosis with eventual bone-resorption and implant failure,
      respectively. Thus, in order to combat aforementioned complications, present
      research aims in utilizing antioxidant ceria (CeO2) and antibacterial silver (Ag)
      reinforced hydroxyapatite (HA) composite with enhanced mechanical and
      cytocompatible properties. Highly dense (>90%) spark plasma sintered HA-based
      composites elicits enhanced elastic modulus (121-133 GPa) in comparison to that
      of HA. The antioxidant activity is quantified using ceria alone, wherein HA-ceria
      and HA-ceria-Ag pellets exhibits ~36 and 30% antioxidant activity, respectively,
      accrediting ceria as a scavenger of reactive oxygen species, which was
      corroborated with the % Ce3+ change quantified by X-ray photoelectron
      spectroscopy. The HA-Ag pellet shows antibacterial efficacy of ~61% for E. coli
      and ~53% for S. aureus, while a reduction of ~59% for E. coli and ~50% for S.
      aureus is observed for HA-ceria-2.5Ag pellet, affirming Ag reinforcement as an
      established bactericidal agent. The enhanced hydrophobicity on all the HA-based
      composites affords a high protein adsorption (24 h incubation). Further, elevated
      hFOB cell count (~6.7 times for HA-ceria-Ag on day 7) with filopodial extensions
      (60-150 MUm) and matrix-like deposition reflect cell-substrate intimacy. Thus,
      synergistic antioxidant ceria and antibacterial Ag reinforcement with enhanced
      mechanical integrity can potentially serve as cytocompatible porous bone
      scaffolds or bioactive coatings on femoral stems.

PMID- 29636128
TI  - Novel biocatalytic systems for maintaining the nucleotide balance based on
      adenylate kinase immobilized on carbon nanostructures.
AB  - In this study graphene oxide (GO), carbon quantum dots (CQD) and carbon
      nanoonions (CNO) have been characterized and applied for the first time as a
      matrix for recombinant adenylate kinase (AK, EC 2.7.4.3) immobilization. AK is an
      enzyme fulfilling a key role in metabolic processes. This phosphotransferase
      catalyzes the interconversion of adenine nucleotides (ATP, ADP and AMP) and
      thereby participates in nucleotide homeostasis, monitors a cellular energy charge
      as well as acts as a component of purinergic signaling system. The AK activity in
      all obtained biocatalytic systems was higher as compared to the free enzyme. We
      have found that the immobilization on carbon nanostructures increased both
      activity and stability of AK. Moreover, the biocatalytic systems consisting of AK
      immobilized on carbon nanostructures can be easily and efficiently lyophilized
      without risk of desorption or decrease in the catalytic activity of the
      investigated enzyme. The positive action of AK-GO biocatalytic system in
      maintaining the nucleotide balance in in vitro cell culture was proved.

PMID- 29636129
TI  - Macroporous click-elastin-like hydrogels for tissue engineering applications.
AB  - Elastin is a key extracellular matrix (ECM) protein that imparts functional
      elasticity to tissues and therefore an attractive candidate for bioengineering
      materials. Genetically engineered elastin-like recombinamers (ELRs) maintain
      inherent properties of the natural elastin (e.g. elastic behavior, bioactivity,
      low thrombogenicity, inverse temperature transition) while featuring precisely
      controlled composition, the possibility for biofunctionalization and non-animal
      origin. Recently the chemical modification of ELRs to enable their crosslinking
      via a catalyst-free click chemistry reaction, has further widened their
      applicability for tissue engineering. Despite these outstanding properties, the
      generation of macroporous click-ELR scaffolds with controlled, interconnected
      porosity has remained elusive so far. This significantly limits the potential of
      these materials as the porosity has a crucial role on cell infiltration,
      proliferation and ECM formation. In this study we propose a strategy to overcome
      this issue by adapting the salt leaching/gas foaming technique to click-ELRs. As
      result, macroporous hydrogels with tuned pore size and mechanical properties in
      the range of many native tissues were reproducibly obtained as demonstrated by
      rheological measurements and quantitative analysis of fluorescence, scanning
      electron and two-photon microscopy images. Additionally, the appropriate size and
      interconnectivity of the pores enabled smooth muscle cells to migrate into the
      click-ELR scaffolds and deposit extracellular matrix. The macroporous structure
      together with the elastic performance and bioactive character of ELRs, the
      specificity and non-toxic character of the catalyst-free click-chemistry
      reaction, make these scaffolds promising candidates for applications in tissue
      regeneration. This work expands the potential use of ELRs and click chemistry
      systems in general in different biomedical fields.

PMID- 29636130
TI  - Dispersion of multi-walled carbon nanotubes in [BMIM]PF6 for electrochemical
      sensing of acetaminophen.
AB  - The influence of functionalized multi-walled carbon nanotubes (fMWCNT) in the
      presence of 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIM]PF6) in
      different ratios was investigated on the acetaminophen (ACOP) electrochemical
      determination. The electrochemical behavior of the ACOP exhibited a pair of well
      defined redox peaks, suggesting that the reversibility of ACOP was significantly
      improved in comparison to irreversible oxidation peak on bare GCE. The redox
      process was controlled by adsorption, involves two electrons and the value of
      apparent rate constant (ks) was equal to 14.7 s-1 +/- 3.6 s-1. The analytical
      curves were obtained for concentrations of ACOP ranging from 0.3 to 3.0 MUmol L
      1. The values of the detection limit were calculated from SWV and found to be
      6.73 * 10-8 mol L-1. The proposed electrochemical sensor exhibited good stability
      and reproducibility and was applied for ACOP determination in tablets (Tylenol(r)
      and Tylenol(r)DC) with satisfactory results.

PMID- 29636131
TI  - 2-Thiophene ethylamine modified hyaluronic acid with its application on
      hepatocytes culture.
AB  - Hyaluronic acid (HA) is a component of extracellular matrix, which is important
      for cell functions and tissue integrity. Biosynthesized HA, as well as its
      derivatives, is widely used in cosmetics industry, biochemical medicine and
      medical surgery. In this research, we report a new hyaluronic acid derivative
      synthesized by amidation of hyaluronic acid with 2-thiophene ethylamine (2TEA). 2
      chloro-dimethoxy-1,3,5-triazine (CDMT) served as the activating agent of the
      carboxylic groups. Primary mouse hepatocytes cultured with this derivative HA
      2TEA maintained their epithelial morphology and showed better hepatic functions.
      This result was confirmed by the higher expression levels of hepatic functional
      genes in primary hepatocyte cultured with HA-2TEA derivative. Moreover, the
      protein levels of several hepatic genes were further confirmed by
      immunofluorescence staining. Thus HA-2TEA(2-thiopheneethylamine) derivative
      demonstrated good capacity on hepatocytes culture, and maintained hepatocyte
      functions in vitro.

PMID- 29636133
TI  - Selected developments and medical applications of organic-inorganic hybrid
      biomaterials based on functionalized spherosilicates.
AB  - Well-defined and tailor-made spherosilicates and POSS-based (POSS = Polyhedral
      Oligomeric Silsesquioxanes) (nano)composites with interesting chemical and
      mechanical properties have applications in the widely-regarded field of
      innovative biomaterials. They can serve as delivery systems, three-dimensional
      scaffolds for specific tissue engineering, biomaterials for orthopedic,
      cardiovascular, and reconstructive surgery, etc. Such organic-inorganic hybrids
      are much more effective biomaterials than pure polymers, bioglasses, metals,
      alloys, and ceramics currently used in medical applications and are considered as
      next-generation systems in innovative medical approaches. This range of
      applications creates a strong impetus for novel, cheap, and easy-to-scale-up
      methods for their synthesis. In this review (highlights since 2006), selected
      biomaterials consisting of various polymeric derivatives such as
      polymethacrylates, polylactides, polycaprolactones, polyurethanes, etc., which
      serve as organic side-arms of POSS and can create polymer platforms for precisely
      localized spherosilicates among organic matrices, are discussed as a new
      generation of silicon-based biosystems using spherosilicates, promising
      biomaterials with a particular use in soft- and hard-tissue engineering.

PMID- 29636132
TI  - Effects of polycaprolactone on alendronate drug release from Mg-doped
      hydroxyapatite coating on titanium.
AB  - The scientific objective of this study was to understand the influence of PCL
      coating on alendronate drug release kinetics in vitro. Our hypothesis was PCL
      coating would minimize burst release of alendronate from plasma sprayed Mg-doped
      hydroxyapatite (HA) coated commercially pure titanium (CpTi) samples. In the US
      alone, over 44 million women and men aged 50 and older are affected by
      osteoporosis which can lead to replacement and/or revision surgeries. Alendronate
      is a widely-used drug for treating osteoporosis and would be an ideal drug to be
      loaded and released from these replacement systems. Initial burst release is a
      common phenomenon for the most drug loaded devices. To modulate the release
      kinetics, a biodegradable polymer, polycaprolactone (PCL), coating with slow
      degradable kinetics was employed. Samples with 2 and 4 wt% PCL showed about 34%
      and 26% release of alendronate within the first 24 h, respectively, compared to
      75% burst release without any PCL coating. With the addition of a PCL coating, a
      controlled release kinetics of alendronate was achieved from HA coated titanium
      implants, which can potentially impact millions of patients worldwide having
      compromised bone due to osteoporosis.

PMID- 29636134
TI  - Understanding and augmenting the stability of therapeutic nanotubes on anodized
      titanium implants.
AB  - Titanium is an ideal material choice for orthopaedic and dental implants, and
      hence a significant amount of research has been focused towards augmenting the
      therapeutic efficacy of titanium surfaces. More recently the focus has shifted to
      nano-engineered implants fabricated via anodization to generate self-ordered
      nanotubular structures composed of titania (TiO2). These structures (titania
      nanotubes/TNTs) enable local drug delivery and tailorable cellular modulation
      towards achieving desirable effects like enhanced osseointegration and
      antibacterial action. However, the mechanical stability of such modifications is
      often ignored and remains underexplored, and any delamination or breakage in the
      TNTs modification can initiate toxicity and lead to severe immuno-inflammatory
      reactions. This review details and critically evaluates the progress made in
      relation to this aspect of TNT based implants, with a focus on understanding the
      interface between TNTs and the implant surface, treatments aimed at augmenting
      mechanical stability and strategies for advanced mechanical testing within the
      bone micro-environment ex vivo and in vivo. This review article extends the
      existing knowledge in this domain of TNTs implant technology and will enable
      improved understanding of the underlying parameters that contribute towards
      mechanically robust nano-engineered implants that can withstand the forces
      associated with implant surgical placement and the load bearing experienced at
      the bone/implant interface.

PMID- 29636135
TI  - BisGMA analogues as monomers and diluents for dental restorative composite
      materials.
AB  - Current commercially available dental composite materials have certain
      limitations for their use, including high monomer viscosity and high
      polymerization shrinkage, resulting in residual stresses and interfacial gaps.
      This study focused on the chemical modification of resin monomer bisphenol A
      glycidyl methacrylate (bisGMA), so as to reduce the viscosity and polymerization
      shrinkage. In this design, the hydroxyl groups of bisGMA were transformed into
      ester groups with various alkyl chain length and branching. The modified monomers
      showed promising properties including reduced viscosity, reduced polymerization
      shrinkage, increased hydrophobicity, increased degree of double bond conversion,
      and improved mechanical properties of the resulting dental resin composites. The
      structure/property relationships of the new monomers were investigated, and
      optimal monomer structures were identified for dental composites with improved
      properties.

PMID- 29636136
TI  - Enhanced cellular uptake of LHRH-conjugated PEG-coated magnetite nanoparticles
      for specific targeting of triple negative breast cancer cells.
AB  - Targeted therapy is an emerging technique in cancer detection and treatment. This
      paper presents the results of a combined experimental and theoretical study of
      the specific targeting and entry of luteinizing hormone releasing hormone (LHRH)
      conjugated PEG-coated magnetite nanoparticles into triple negative breast cancer
      (TNBC) cells and normal breast cells. The conjugated nanoparticles structures,
      cellular uptake of PEG-coated magnetite nanoparticles (MNPs) and LHRH-conjugated
      PEG-coated magnetite nanoparticles (LHRH-MNPs) into breast cancer cells and
      normal breast cells were investigated using a combination of transmission
      electron microscope, optical and confocal fluorescence microscopy techniques. The
      results show that the presence of LHRH enhances the uptake of LHRH-MNPs into TNBC
      cells. Nanoparticle entry into breast cancer cells is also studied using a
      combination of thermodynamics and kinetics models. The trends in the predicted
      nanoparticle entry times (into TNBC cells) and the size ranges of the engulfed
      nanoparticles (within the TNBC cells) are shown to be consistent with
      experimental observations. The implications of the results are then discussed for
      the specific targeting of TNBCs with LHRH-conjugated PEG-coated magnetite
      nanoparticles for the early detection and treatment of TNBC.

PMID- 29636137
TI  - Composite scaffold of micronized porcine cartilage/poly(lactic-co-glycolic acid)
      enhances anti-inflammatory effect.
AB  - The main disadvantage of using poly(lactic-co-glycolic acid) (PLGA), a typical
      synthetic polymer, as a biomaterial is that it induces inflammation. To overcome
      this disadvantage, we determined the ability of micronized porcine cartilage
      (MPC) for alleviating the inflammatory effects of a PLGA scaffold. MPC was
      analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Fourier
      transform-infrared spectroscopy, and typical collagen components were confirmed.
      The MPC/PLGA scaffolds were fabricated using various concentrations of MPC and
      the compressive strength was evaluated to characterize its physical properties.
      Although the compressive strength decreased with increasing amounts of MPC, the
      roughness of the surface, assessed by scanning election microscopy, was
      considered to be suitable for facilitating cell attachment. Notably, in vitro
      experiments showed that the cell adhesion and proliferation rates increased as
      the MPC content increased. MPC further reduced gene expression levels of
      inflammatory cytokines and cellular reactive oxygen species, as determined by
      real time-polymerase chain reaction and fluorescence-activated cell sorting,
      respectively. In addition, in vivo experiments confirmed the interaction between
      tissues and the scaffolds. Overall, these results confirmed that the MPC/PLGA
      scaffold is superior to the PLGA scaffold in many respects and might be a
      suitable candidate for resolving the disadvantages of PLGA in tissue engineering
      applications.

PMID- 29636138
TI  - Assessment of calcium sulfate hemihydrate-Tricalcium silicate composite for bone
      healing in a rabbit femoral condyle model.
AB  - Calcium sulfate or plaster of Paris (POP) is considered as a bone cement with a
      fast degradation rate, which frequently makes it resorb before the bone defect
      area is completely filled by new bone. The incorporation of tricalcium silicate
      (C3S) into POP cement has been proven as a feasible approach to reduce the in
      vitro degradation rate and improve the in vitro bioactivity of the material.
      However, the in vivo performance of the POP/C3S composite cement is still
      unclear. Therefore, the aim of the present study is to assess the
      biodegradability and osteogenesis of POP/C3S composite cement in comparison with
      those of POP bone cement. To carry out the in vivo evaluation, POP and POP/C3S
      cements were implanted into a femoral condyle defect model in rabbits (5 mm
      diameter * 10 mm length) for 4, 8, and 12 weeks duration. The area of the
      remaining cement and new bone regeneration in bone defect were investigated and
      quantitatively measured using radiography, micro-computed tomography, and
      histological staining. For both cements, no sign of inflammation was observed.
      POP cement was completely degraded at the 8th week of post-implantation. By
      contrast, only approximately 50% by volume of POP/C3S composite cement degraded
      at the 12th week, which allowed a long-term framework for new bone formation. The
      osteogenic ability of POP/C3S composite cement was significantly superior to that
      of POP as indicated by the higher mineralization rate and maturity of the newly
      formed bone around the composite cement. In summary, our findings demonstrated
      that the in vivo degradation behaviors and osteogenic ability of POP cement could
      be improved by incorporating C3S in vivo, suggesting that POP/C3S composite
      cement has potential as a biodegradable cement for bone repair.

PMID- 29636139
TI  - Novel bifurcation stents coated with bioabsorbable nanofibers with extended and
      controlled release of rosuvastatin and paclitaxel.
AB  - A novel bifurcation stent coated with bioabsorbable nanofibers that deliver the
      extended and controlled release of rosuvastatin and paclitaxel was developed.
      Bioabsorbable bifurcation stents, consisting of a double-slit tubular main body
      and two spiral branches, were manufactured. Bi-layered poly (lactic-co-glycolic
      acid) nanofibers that contained rosuvastatin and paclitaxel were used for
      treating the stents. Various properties of the fabricated stents, including
      compression strengths, collapse pressure, water contact angle and flow properties
      within a circulation model, were quantified. In vitro nanofibrous elution
      chromatography assays from the drug-loading bifurcation stents were carried out
      for the release patterns of pharmaceuticals. The effectiveness of eluted
      rosuvastatin and paclitaxel in inhibiting the adhesion of platelets as well as
      the proliferation of smooth muscle cells (SMCs) were studied, respectively. The
      experimental results suggest that bioabsorbable nanofibrous bifurcation stents
      released high concentrations of rosuvastatin and paclitaxel for 27 and 70 days,
      respectively. The eluted drugs of rosuvastatin and paclitaxel effectively reduced
      adherent platelets and the proliferation of SMCs. The developed bioabsorbable
      nanofibrous bifurcation stents herein may provide a promising means of treating
      cardiovascular bifurcation lesions.

PMID- 29636140
TI  - One-step fabrication of functionalized poly(etheretherketone) surfaces with
      enhanced biocompatibility and osteogenic activity.
AB  - Polyetheretherketone (PEEK) has an elastic modulus similar to that of the bone;
      however, its use as a material for bone repair is limited by bio-inert surface
      chemistry and poor osteogenesis-inducing capacity. To address this issue, the
      PEEK surface was activated by ultraviolet radiation-induced grafting of
      methacrylated hyaluronic acid (MeHA) and titanium dioxide (TiO2) nanofibers via a
      one-step process. The modified PEEK surface was characterized by X-ray
      photoelectron and Fourier-transform infrared spectroscopy, and the extent of
      surface modification was evaluated by measuring static contact angles. Atomic
      force microscopy revealed that the PEEK surface grafted with electrospun TiO2 had
      abundant nanofibers and a roughness that was comparable to that of human cortical
      bone. In vitro experiment, rat bone mesenchymal stem cells showed increased
      adhesion, proliferation, and osteogenic differentiation capacity on TiO2-modified
      as compared to unmodified PEEK. Thus, PEEK that is surface-modified with
      electrospun TiO2 and MeHA has enhanced biocompatibility and can be an effective
      material for use in orthopedic implants and medical devices.

PMID- 29636141
TI  - Repair of full-thickness articular cartilage defect using stem cell-encapsulated
      thermogel.
AB  - Cartilage defect repair by hydrogel-based tissue engineering is becoming one of
      the most potential treatment strategies. In this work, a thermogel of triblock
      copolymer poly(lactide-co-glycolide)-block-poly(ethylene glycol)-block
      poly(lactide-co-glycolide) (PLGA-PEG-PLGA) was prepared as scaffold of bone
      marrow mesenchymal stem cells (BMMSCs) for repair of full-thickness articular
      cartilage defect. At first, the copolymer solution showed a reversible sol-gel
      transition at physiological temperature range, and the mechanical properties of
      such thermogel were high enough to support the repair of cartilage. Additionally,
      excellent biodegradability and biocompatibility of the thermogel were
      demonstrated. By implanting the BMMSC-encapsulated thermogel into the full
      thickness articular cartilage defect (5.0 mm in diameter and 4.0 mm in depth) in
      the rabbit, it was found that the regenerated cartilage integrated well with the
      surrounding normal cartilage and subchondral bone at 12 weeks post-surgery. The
      upregulated expression of glycosaminoglycan and type II collagen in the repaired
      cartilage, and the comparable biomechanical properties with normal cartilage
      suggested that the cell-encapsulated PLGA-PEG-PLGA thermogel had great potential
      in serving as the promising scaffold for cartilage regeneration.

PMID- 29636142
TI  - Novel antibacterial biodegradable Fe-Mn-Ag alloys produced by mechanical
      alloying.
AB  - Various compositions and synthesis methods of biodegradable iron-based alloys
      have been studied aiming for the use of temporary medical implants. However, none
      is focused on nano-structured alloy and on adding antibacterial property to the
      alloy. In this study, new Fe-30Mn-(1-3)Ag alloys were synthesized by means of
      mechanical alloying and assessed for their microstructure, mechanical properties,
      corrosion rate, antibacterial activity and cytotoxicity. Results showed that the
      alloy with 3 wt% Ag content displayed the highest relative density, shear
      strength, micro hardness and corrosion rate. However, optimum cytotoxicity and
      the antibacterial activity were reached by the alloy with 1 wt% Ag content. The
      compositional and processing effects of the alloys' properties are further
      discussed in this work.

PMID- 29636144
TI  - Facial Plastic Surgery Controversies: Keloids.
AB  - There are more than 11 million people in the world affected with keloids.
      Nevertheless, there is a lack of agreement in keloid management. Moreover, keloid
      research has left gaps in the understanding of its pathogenesis. Six questions
      are answered by 3 clinical scientists in an attempt to address common keloid
      controversies.

PMID- 29636143
TI  - Open porous dealloying-based biomaterials as a novel biomaterial platform.
AB  - The close match of stiffness between implant material and bone is critically
      important to avoid stress-shielding effect and ensure a fast healing of injured
      tissues. Here, we introduce liquid metal dealloying method for synthesis of
      robust open porous biomaterials possessing low Young's modulus. The remarkable
      advantage of the liquid metal dealloying method is a large flexibility in
      selecting chemical composition of a desired porous biomaterial together with
      unique tunable microstructure. To demonstrate the versatility of the method, a
      number of open porous TixZr100-x alloys with different chemical compositions and
      microstructural characteristics was developed by dealloying precursor (TixZr100
      x)yCu100-y alloys in liquid magnesium. The effects of the processing conditions
      and the precursors' chemical composition on the microstructure of the porous
      TixZr100-x as well as their mechanical behavior were discussed in detail. In
      particular, the porous TixZr100-x distinguish themselves due to a low and tunable
      stiffness ranging from 3.2 to 15.1 GPa and a rather high strength reaching up to
      480 MPa. This unique combination of mechanical properties of the new open porous
      TixZr100-x alloys becomes even more interesting in view of preliminary biological
      tests highlighting their excellent cytocompatibility. Overall, the liquid metal
      dealloying provides an opportunity for designing a new biomaterials platform with
      flexible tunable functionality.

PMID- 29636145
TI  - Contemporary Laser and Light-Based Rejuvenation Techniques.
AB  - Laser and light skin rejuvenation have changed dramatically in the last 10 years.
      CO2 and erbium:YAG remain the main wavelengths, but fractional, nonablative, and
      combination devices have been added. For those patients with lighter skin types
      and extensive photodamage and rhytids, full-field ablative laser resurfacing
      remains the procedure of choice. For those seeking less downtime and risks,
      fractional devices offer an excellent and growing alternative, although multiple
      treatments may be required for optimal results. A new generation of hybrid and
      nonablative devices offers many advantages, yet many of these results may be
      duplicated with well-proven intense pulsed light.

PMID- 29636146
TI  - Radiofrequency Technology in Face and Neck Rejuvenation.
AB  - Three doctors discuss the current issues and controversies involving the use of
      radiofrequency and energy-based devices for skin tightening, facial contouring,
      and other indications. The use of transcutaneous monopolar-, bipolar-, multipolar
      , subcutaneous-, and microneedle-based delivery methods are discussed. The
      controversies involved in the various devices are discussed.

PMID- 29636147
TI  - The Superficial Musculoaponeurotic System and Other Considerations in
      Rejuvenation of the Lower Face and Neck.
AB  - This article addresses several facelift challenges involving anatomic conditions,
      including platysma banding, endomorphic facial habitus, and midface hypoplasia.
      In addition, patient counseling and conveying realistic expectations about
      limitations of facelift alone, with and without adjunctive procedures, are
      presented. In addition, a few technical modifications of the facelift procedure
      contributing to more uniform success and longevity are discussed.

PMID- 29636148
TI  - Facial Paralysis Discussion and Debate.
AB  - This article examines 6 questions about facial paralysis answered by 3 experts in
      their field of facial plastic surgery. The topics covered include routine
      assessment, neuromuscular training, nonsurgical management, and the future of
      this field. All the authors answered these questions in a "How I do it" manner to
      provide the reader with a true understanding of their thoughts and techniques.
      This article provides a practical resource to all physicians and practitioners
      treating patients with facial paralysis on some of the most common questions and
      issues.

PMID- 29636149
TI  - Management of the Prominent Ear.
AB  - This article incorporates the opinions and preferred surgical options in managing
      patients of 3 prominent facial plastic surgeons who have large otoplasty
      practices. Six different questions covering the management of prominent ears are
      answered by the 3 practitioners. Nonsurgical options for the treatment of
      prominent ears are discussed. The role of cartilage-cutting and cartilage-sparing
      techniques as well as individual preferred otoplasty techniques are thoroughly
      covered. Postoperative management of these patients is presented by the
      individual surgeons.

PMID- 29636150
TI  - Lip Augmentation.
AB  - This article examines 6 questions about lip augmentation answered by 3 experts in
      their field of facial plastic surgery. The topics covered include high-yield
      areas such as injection, surgical enhancement, rhytid resurfacing, implants,
      complications, and technique changes over the years. All the authors answered
      these questions in a "How I do it" manner to provide the reader with a true
      understanding of their thoughts and techniques. This article provides a practical
      resource to all physicians and practitioners performing lip augmentation on some
      of the most common questions and issues.

PMID- 29636151
TI  - Grafting Techniques in Primary and Revision Rhinoplasty.
AB  - With the adoption of open structure techniques, rhinoplasty has become more
      reliant on the use of structural grafts to resist change that occurs over time
      owing to both gravity and the aging process. As surgical procedures have become
      more technically complex, the type of grafts use for both primary and secondary
      rhinoplasty have undergone significant evolution. This article provides a case
      approach focused on the use of structural grafting in rhinoplasty.

PMID- 29636152
TI  - Injectable Fillers: Panel Discussion, Controversies, and Techniques.
AB  - Injectable products are now being designed to treat specific areas of the face,
      including the lower lid/cheek region, the midface, and circumoral rhytids. Expert
      injectors from 3 core disciplines (facial plastic surgery, oculoplastic surgery,
      and dermatology) were asked to discuss their approaches to the midface, lower
      lid, and cheek region and their opinions about using cannulas versus needles. The
      authors describe their techniques for avoiding and managing filler complications.
      They give insight into how their techniques have changed over the past few years
      and their use of new products that have been developed.

PMID- 29636153
TI  - Orbital Fractures.
AB  - Anatomic, rather than volumetric, reconstruction leads to improved outcomes in
      orbital reconstruction. Endoscopic visualization improves lighting and
      magnification of the surgical site and allows the entire operative team to
      understand and participate in the procedure. Mirror-image overlay display with
      navigation-guided surgery allows in situ fine adjustment of the implant contours
      to match the contralateral uninjured orbit. Precise exophthalmometry is important
      before, during, and after surgery to provide optimal surgical results.

PMID- 29636154
TI  - Evaluating New Technology.
AB  - There are multiple complex issues to consider when evaluating any new technology.
      First evaluate the efficacy of the device. Then considering your patient
      population decide whether this technology brings an added benefit to your
      patients. If it meets these 2 criteria, then proceed to the financial analysis of
      acquiring this technology. The complete financial analysis has several important
      components that include but are not limited to cost, value, alternatives, return
      on investment, and associated marketing expense.

PMID- 29636155
TI  - Controversies in Facial Plastic Surgery.

PMID- 29636156
TI  - Implementation of safety management systems in Hong Kong construction industry -
      A safety practitioner's perspective.
AB  - INTRODUCTION: In the 1980s, the safety management system (SMS) was introduced in
      the construction industry to mitigate against workplaces hazards, reduce the risk
      of injuries, and minimize property damage. Also, the Factories and Industrial
      Undertakings (Safety Management) Regulation was introduced on 24 November 1999 in
      Hong Kong to empower the mandatory implementation of a SMS in certain industries
      including building construction. Therefore, it is essential to evaluate the
      effectiveness of the SMS in improving construction safety and identify the
      factors that influence its implementation in Hong Kong. METHOD: A review of the
      current state-of-the-practice helped to establish the critical success factors
      (CSFs), benefits, and difficulties of implementing the SMS in the construction
      industry, while structured interviews were used to establish the key factors of
      the SMS implementation. RESULTS: Results of the state-of-the-practice review and
      structured interviews indicated that visible senior commitment, in terms of
      manpower and cost allocation, and competency of safety manager as key drivers for
      the SMS implementation. More so, reduced accident rates and accident costs,
      improved organization framework, and increased safety audit ratings were
      identified as core benefits of implementing the SMS. Meanwhile, factors such as
      insufficient resources, tight working schedule, and high labor turnover rate were
      the key challenges to the effective SMS implementation in Hong Kong. PRACTICAL
      APPLICATIONS: The findings of the study were consistent and indicative of the
      future development of safety management practice and the sustainable safety
      improvement of Hong Kong construction industry in the long run.

PMID- 29636157
TI  - Evaluating an intervention to improve belt fit for adult occupants: Promoting
      positive beliefs.
AB  - INTRODUCTION: Seat belt use provides significant public health benefit, however,
      most public awareness campaigns have generally focused on seat belt use rather
      than encouraging adults to improve seat belt fit with belt placement. This study
      provides an evaluation of a video-based intervention to improve adult belt fit
      assessing whether a video-based intervention can target beliefs and knowledge of
      seat belt placement and be perceived as relevant by the target audience. METHOD:
      An intervention group of 29 adults (15 women and 14 men) and a comparison group
      of 99 adults (41 women and 47 men) participated. RESULTS: The intervention group
      had significantly more favorable beliefs around belt fit than the comparison
      group related to Health Belief Model constructs of higher self-efficacy, greater
      benefits, and fewer barriers. The intervention group was also significantly
      better at accurately drawing belt fit than the comparison group. The video
      intervention was described as relevant, interesting, and the intervention group
      favored the provision of a diverse sample of models in the intervention.
      CONCLUSIONS: Overall, the study provides insight into relevant target beliefs for
      an intervention focused on belt fit and suggests that a brief video-based
      intervention in the style of a public service announcement may be effective in
      promoting positive beliefs and knowledge around belt fit. Future efforts should
      confirm these findings with a larger sample size spanning multiple geographic and
      demographic areas. PRACTICAL APPLICATIONS: These findings can help better inform
      intervention initiatives to improve occupant belt fit.

PMID- 29636158
TI  - The effect of fatigue driving on injury severity considering the endogeneity.
AB  - INTRODUCTION: Fatigue driving is one of the most risky driving-related behaviors
      and represented a significant social and economic cost to the community. Several
      studies have already examined the relationship between fatigue driving behavior
      and traffic injury severity from different aspects. However, fatigue driving and
      injury severity in traffic crash may share some common influential factors.
      Ignoring the impact of these common factors will lead to endogeneity problem and
      result in biased parameter estimation. METHOD: Based on 38,564 crash records
      during 2006-2011 in Guangdong province, China, we apply a bivariate endogenous
      binary-ordered probit model to examine the relationship between fatigue driving
      and injury severity considering endogeneity of fatigue driving. We also explore
      the difference of influential factors between commercial and non-commercial
      vehicle drivers. RESULTS: This study identifies several common observed
      influential factors of fatigue driving propensity and fatal injury propensity and
      reveals a substantial and significant negative correlation of unobserved factors
      between them. CONCLUSIONS: The influence of fatigue driving on injury severity is
      significantly underestimated if the endogeneity of fatigue driving on fatal
      injury propensity is ignored. Factors such as vehicle insurance and road types
      not only affect fatal injury propensity, but also fatigue driving propensity.
      PRACTICAL APPLICATIONS: The findings in this study can help better understand how
      those factors affect fatigue driving and injury severity, and contributes to more
      efficient policy for preventing the harmfulness of fatigue-related crashes.

PMID- 29636159
TI  - Passenger use of and attitudes toward rear seat belts.
AB  - OBJECTIVES: This study sought to identify attitudes toward belt use in the rear
      seat and to gain insight into the experiences of rear-seat passengers. METHOD: A
      telephone survey conducted between June and August 2016 targeted adult passengers
      who had recently ridden in the rear and who did not always wear their seat belt
      when doing so. Respondents were questioned regarding their reasons for not
      buckling up and possible conditions under which they would be more likely to
      buckle up during rear-seat travel. RESULTS: Of 1163 recent rear-seat passengers,
      72% reported always using their seat belt in the rear. Full-time belt use was
      lower among passengers who primarily travel in the rear of hired vehicles
      compared with personal vehicles. The most common explanation for not buckling up
      was that the back seat is safer than the front. Four out of five agreed they do
      not buckle up because of type of trip; two-thirds forget or do not see the need;
      and two-thirds agreed with reasons related to design, comfort, or usability
      issues. Nearly 40% agreed that they sometimes do not buckle up in the rear
      because there is no law requiring it. CONCLUSION: Many reasons for not using
      belts in the rear are similar to reasons in the front, such as forgetfulness,
      inconvenience, or discomfort. One difference is that many rear-seat passengers
      perceive using the belt is unnecessary because the back seat is safer than the
      front. More than half of part-time belt users and nonusers reported interventions
      such as rear seat belt reminders, stronger belt-use laws, and more comfortable
      belts would make them more likely to use their seat belt in the rear seat.
      Practical applications: This study identifies barriers to rear seat belt use that
      point to the need for a multi-faceted approach to increase belt use.

PMID- 29636160
TI  - Estimating safety effects of adaptive signal control technology using the
      Empirical Bayes method.
AB  - INTRODUCTION: Adaptive signal control technology (ASCT) has long been
      investigated for its operational benefits, but the safety impacts of this
      technology are still unclear. The main purpose of this study was to determine the
      safety effect of ASCT at urban/suburban intersections by assessing two different
      systems. METHOD: Crash data for 41 intersections from the Pennsylvania Department
      of Transportation (PennDOT), along with crash frequencies computed through Safety
      Performance Functions (SPFs), were used to perform the Empirical Bayes (E-B)
      method to develop crash modification factors (CMF) for ASCT. Moreover, a crash
      type analysis was conducted to examine the safety impact of ASCT on a regional
      scale and the variation of safety among type of crashes observed. RESULTS: The
      results from this study indicated the potential of ASCT to reduce crashes since
      the Crash Modification Factor (CMF) values for both ASCT systems (SURTRAC and
      InSync) showed significant reductions in crashes. Average CMF values of 0.87 and
      0.64 were observed for total and fatal and injury crash categories at a 95%
      confidence level, and results were consistent between systems. While a reduction
      in the proportion of rear end crashes was observed, the change was not determined
      to be statistically significant. The overall distribution of crash types did not
      change significantly when ASCT was deployed. CONCLUSION AND PRACTICAL
      APPLICATION: The results indicate that safety benefits of ASCT were generally
      consistent across systems, which should aid agencies in making future deployment
      decisions on ASCT.

PMID- 29636161
TI  - Workplace bullying in risk and safety professionals.
AB  - INTRODUCTION: Previous research demonstrates that workplace bullying impacts the
      welfare of victimized employees, with further consequences for the organization
      and profession. There is, however, a paucity of information relating to the
      bullying directed at risk and safety professionals. The present study was
      conducted to address this issue. METHOD: Risk and safety professionals (N=420)
      completed the Negative Acts Questionnaire - Revised and Brief Cope, and reported
      the extent to which they had been pressured to make or amend a risk or safety
      based decision. RESULTS: Those experiencing workplace bullying were more likely
      to engage in a range of coping behaviors, with exposure to work-related and
      personal bullying particularly influential. Workplace bullying also predicted
      pressure to make or change a risk or safety based decision. Work related and
      physically intimidating bullying were particularly important for this aspect of
      professional practice. CONCLUSIONS: Findings are discussed with regard to current
      practice and the support available to risk and safety professionals. PRACTICAL
      APPLICATIONS: Risk and safety professionals require additional support in
      relation to workplace bullying and specifically guidance to resist pressure to
      make or change a risk or safety based decision.

PMID- 29636162
TI  - Built environment effects on bike crash frequency and risk in Beijing.
AB  - INTRODUCTION: Building a safe biking environment is crucial to encouraging
      bicycle use. In developed areas with higher density and more mixed land use, the
      built environment factors that pose a crash risk may vary. This study
      investigates the connection between biking risk factors and the compact built
      environment, using data for Beijing. METHOD: In the context of China, this paper
      seeks to answer two research questions. First, what types of built environment
      factors are correlated with bike-automobile crash frequency and risk? Second, how
      do risk factors vary across different types of bikes? Poisson lognormal random
      effects models are employed to examine how land use and roadway design factors
      are associated with the bike-automobile crashes. RESULTS: The main findings are:
      (1) bike-automobile crashes are more likely to occur in densely developed areas,
      which is characterized by higher population density, more mixed land use, denser
      roads and junctions, and more parking lots; (2) areas with greater ground transit
      are correlated with more bike-automobile crashes and higher risks of involving in
      collisions; (3) the percentages of wider streets show negative associations with
      bike crash frequency; (4) built environment factors cannot help explain factors
      contributing to motorcycle-automobile crashes. PRACTICAL APPLICATIONS: In China's
      dense urban context, important policy implications for bicycle safety improvement
      drawn from this study include: prioritizing safety programs in urban centers,
      applying safety improvements to areas with more ground transit, placing bike
      automobile crash countermeasures at road junctions, and improving bicycle safety
      on narrower streets.

PMID- 29636163
TI  - Pedestrian crossing behaviors at uncontrolled multi-lane mid-block crosswalks in
      developing world.
AB  - INTRODUCTION: The gap acceptance theory was primarily used to study pedestrian
      crossing behaviors, in accordance to static gaps that are calculated in the light
      of the cross section of crosswalk. However, pedestrians will face a series of
      dynamic gaps (especially at any uncontrolled multi-lane crosswalk) when they
      decide to cross the street, thus, pedestrians' decisions are made based on the
      dynamic gaps of each lane. METHOD: Pedestrians' crossing behaviors at
      uncontrolled multi-lane mid-block crosswalk were investigated in this study. The
      lane-based gap (LGAP) was defined and five mid-block crosswalks were selected for
      observation in Wuhan, China. Pedestrians' behaviors and the corresponding traffic
      statuses were videoed as collected data, whose statistical analysis indicates
      that most pedestrians choose the rolling gap crossing strategy, which is
      different from existing research. Moreover, a logistic regression model was
      established to evaluate various influencing parameters (such as gender, age,
      waiting time and traffic volume) on the pedestrians' crossing strategy, whose
      accuracy is not satisfying. Therefore, the pedestrian dynamic gap acceptance
      (PDGA) model was put forward to describe pedestrians' crossing behaviors at any
      multi-lane crosswalk based on detailed analysis of the pedestrians' decision
      procedure. RESULTS: The corresponding results show that its accuracy may be up to
      88.6% to well describe pedestrians' crossing behaviors. CONCLUSIONS: The PDGA
      model is appropriate to analyze pedestrians' dynamic decision procedures at multi
      lane mid-block crosswalks. PRACTICAL APPLICATION: The findings of this study can
      be used for safety and performance evaluation of crosswalks at mid-block
      locations in developing countries like China and India.

PMID- 29636164
TI  - Understanding factors associated with misclassification of fatigue-related
      accidents in police record.
AB  - INTRODUCTION: Fatigue is one of the riskiest causes of traffic accidents
      threatening road safety. Due to lack of proper criteria, the identification of
      fatigue-related accidents by police officers largely depends on inferential
      evidence and their own experience. As a result, many fatigue-related accidents
      are misclassified and the harmfulness of fatigue on road safety is misestimated.
      METHOD: In this paper, a joint model framework is introduced to analyze factors
      contributing to misclassification of a fatigue-related accident in police
      reports. Association rule data mining technique is employed to identify the
      potential interactions of factors, and logistic regression models are applied to
      analyze factors that hinder police officers' identification of fatigue-related
      accidents. Using the fatigue-related crash records from Guangdong Province during
      2005-2014, factors contributing to the false positive and false negative
      detection of the fatigue-related accident have been identified and compared.
      RESULTS: Some variables and interactions were identified to have significant
      impacts on fatigue-related accident detection. CONCLUSIONS: Based on the results,
      it can be inferred that the stereotype of certain groups of drivers, crash types,
      and roadway conditions affects police officers' judgment on fatigue-related
      accidents. PRACTICAL APPLICATIONS: This finding can provide useful information
      for training police officers and build better criteria for fatigue
      identification.

PMID- 29636166
TI  - Examining teen driver crashes and the prevalence of distraction: Recent trends,
      2007-2015.
AB  - INTRODUCTION: Teen drivers crash at a much higher rate than adult drivers, with
      distractions found as a factor in nearly 6 out of 10 moderate-to-severe teen
      crashes. As the driving environment continues to rapidly evolve, it is important
      to examine the effect these changes may be having on our youngest and most
      vulnerable drivers. METHOD: The purpose of this study was to identify types of
      vehicle crashes teens are most frequently involved in, as well as the distracting
      activities being engaged in leading up to these crashes, with a focus on
      identifying changes or trends over time. We examined 2,229 naturalistic driving
      videos involving drivers ages 16-19. These videos captured crashes occurring
      between 2007 and 2015. The data of interest for this study included crash type,
      behaviors drivers engaged in leading up to the collision, total duration of time
      the driver's eyes were off the forward roadway, and duration of the longest
      glance away from forward. RESULTS: Rear-end crashes increased significantly
      (annual % change=3.23 [2.40-4.05]), corresponding with national data trends.
      Among cell phone related crashes, a significant shift occurred, from
      talking/listening to operating/looking (annual % change=4.22 [1.15-7.29]). Among
      rear-end crashes, there was an increase in the time drivers' eyes were off the
      road (beta=0.1527, P=0.0004) and durations of longest glances away (beta=0.1020,
      P=0.0014). CONCLUSIONS: Findings suggest that shifts in the way cell phones are
      being used, from talking/listening to operating/looking, may be a cause of the
      increasing number of rear-end crashes for teen drivers. PRACTICAL APPLICATIONS:
      Understanding the role that cell phone use plays in teen driver crashes is
      extremely important. Knowing how and when teens are engaging in this behavior is
      the only way effective technologies can be developed for mitigating these
      crashes.

PMID- 29636165
TI  - Concussion attitudes, behaviors, and education among youth ages 12-17: Results
      from the 2014 YouthStyles survey.
AB  - INTRODUCTION: This study assessed young athletes' (ages 12 to 17) concussion
      attitudes and behaviors, particularly their self-reported experience learning
      about concussion and intentions to report a concussion and disparities in these
      experiences. METHODS: We used data from Porter Novelli's 2014 YouthStyles survey
      that is conducted each year to gather insights about American consumers. RESULTS:
      Of the 1,005 respondents, 57% reported sports participation. Fourteen percent
      reported they may have had a previous concussion, and among them 41% reported
      having a concussion more than once while playing sports. Males (17.7%) were
      significantly more likely to report having a concussion than females (10.0%; chi2
      (1)=7.01, p=0.008). Fifty-five percent of respondents reported having learned
      about what to do if they think they may have a concussion, and 92% reported that
      they would tell their coach if they thought they sustained a concussion while
      playing youth or high school sports. Youth from higher income families ($75,000
      $124,999) were significantly more likely than youth from lower income families
      (less than $35,000) to report that they learned about what do if they suspected
      that they had a concussion. CONCLUSION: Age of athlete, parental income level,
      athlete's sex, and living in a metro versus non-metro area led to disparities in
      athletes' concussion education. There is a need for increased access to
      concussion education and an emphasis on customizing concussion education efforts
      to meet the needs of different groups. PRACTICAL APPLICATION: We identified
      athletes' self-reported previously sustained concussions and predictors of
      education related to concussion. Further research is needed to explore the age,
      gender and income gaps in concussion education among athletes.

PMID- 29636167
TI  - Safety climate and mindful safety practices in the oil and gas industry.
AB  - INTRODUCTION: The existence of a positive association between safety climate and
      the safety behavior of sharp-end workers in high-risk organizations is supported
      by a considerable body of research. Previous research has primarily analyzed two
      components of safety behavior, namely safety compliance and safety participation.
      The present study extends previous research by looking into the relationship
      between safety climate and another component of safety behavior, namely mindful
      safety practices. Mindful safety practices are defined as the ability to be aware
      of critical factors in the environment and to act appropriately when dangers
      arise. METHOD: Regression analysis was used to examine whether mindful safety
      practices are, like compliance and participation, promoted by a positive safety
      climate, in a questionnaire-based study of 5712 sharp-end workers in the oil and
      gas industry. RESULTS: The analysis revealed that a positive safety climate
      promotes mindful safety practices. CONCLUSIONS: The regression model accounted
      for roughly 31% of the variance in mindful safety practices. The most important
      safety climate factor was safety leadership. PRACTICAL APPLICATIONS: The findings
      clearly demonstrate that mindful safety practices are highly context-dependent,
      hence, manageable and susceptible to change. In order to improve safety climate
      in a direction which is favorable for mindful safety practices, the results
      demonstrate that it is important to give the fundamental features of safety
      climate high priority and in particular that of safety leadership.

PMID- 29636168
TI  - Analysis of pedestrian-to-ground impact injury risk in vehicle-to-pedestrian
      collisions based on rotation angles.
AB  - INTRODUCTION: Due to the diversity of pedestrian-to-ground impact (secondary
      impact) mechanisms, secondary impacts always result in more unpredictable
      injuries as compared to the vehicle-to-pedestrian collisions (primary impact).
      The purpose of this study is to investigate the effects of vehicle frontal
      structure, vehicle impact velocity, and pedestrian size and gait on pedestrian-to
      ground impact injury risk. METHOD: A total of 600 simulations were performed
      using the MADYMO multi-body system and four different sizes of pedestrians and
      six types initial gait were considered and impacted by five vehicle types at five
      impact velocities, respectively. The pedestrian rotation angle ranges (PRARs) (a,
      b, c, d) were defined to identify and classify the pedestrian rotation angles
      during the ground impact. RESULTS: The PRARs a, b, and c were the ranges
      primarily observed during the pedestrian landing. The PRAR has a significant
      influence on pedestrian-to-ground impact injuries. However, there was no
      correlation between the vehicle velocity and head injury criterion (HIC) caused
      by the secondary impact. In low velocity collisions (20, 30km/h), the severity of
      pedestrian head injury risk caused by the secondary impact was higher than that
      resulting from the primary impact. CONCLUSIONS: The PRARs defined in this study
      are highly correlated with the pedestrian-to-ground impact mechanism, and can be
      used to further analyze the pedestrian secondary impact and to predict the head
      injury risk. PRACTICAL APPLICATIONS: To reduce the pedestrian secondary impact
      injury risk, passive and active safety countermeasures should be considered
      together to prevent the pedestrian's head-to-ground impacts, particularly in the
      low-velocity collisions.

PMID- 29636169
TI  - Potential effects of lowering the BAC limit on injuries, fatalities, and costs.
AB  - INTRODUCTION: Potential health and cost impacts of lowering the BAC limit for
      U.S. drivers below .08% were explored through analyses of reductions in crash
      incidence, injury severity, and costs based on five scenarios with varying
      assumptions about how the change to a .05% BAC limit might affect alcohol
      impaired driving. METHODS: Distribution of crashes by injury level and highest
      driver or non-occupant BAC levels for 2010, together with unit crash costs
      provided a base for comparison. Scenario 1 assumed all alcohol-impaired driving
      ceased; scenario 2 assumed all drivers obeyed the law, and scenario 3 assumed
      decreases in driver BAC levels would be limited to those who had been driving
      near the legal limit before the change. Scenario 4 was based on changes in driver
      BAC levels associated with a 08% to .05% BAC limit change in Australia, and
      scenario 5 was based on changes in alcohol-related crashes associated with the
      change to the .08% BAC limit in the United States. The number of casualties
      prevented in each scenario was estimated using relative risks of crash
      involvement, and changes in societal costs were estimated using the unit costs.
      RESULTS: Reductions ranging from 71% to 99% in fatalities, injuries, and costs
      related to alcohol-impaired driving were estimated in scenarios 1 and 2.
      Scenarios 3-5 produced smaller reductions ranging from 4% to 16% for alcohol
      impaired fatalities, injuries, and costs. CONCLUSION: The wide difference between
      the outcomes of the two sets of scenarios reflects the sensitivity of BAC policy
      benefits to driver compliance behavior. PRACTICAL APPLICATION: The quantification
      of the reduction in the number and costs of traffic crash casualties in the set
      of behavioral scenarios explored in this research can inform policymakers about
      the extent and limits of benefits achievable by lowering the BAC limits as they
      consider strategies to reduce alcohol-impaired driving.

PMID- 29636170
TI  - A systematic review of socioeconomic status measurement in 13 years of U.S.
      injury research.
AB  - OBJECTIVE: The purpose of this review was to assess the impact of socioeconomic
      status (SES) on injury and to evaluate how U.S. injury researchers have measured
      SES over the past 13years in observational research studies. DESIGN & METHODS:
      This systematic review included 119 US injury studies indexed in PubMed between
      January 1, 2002 and August 31, 2015 that used one or more individual and/or area
      level measures of SES as independent variables. Study findings were compared to
      the results of a previous review published in 2002. RESULTS: Findings indicate
      SES remains an important predictor of injury. SES was inversely related to injury
      in 78 (66%) of the studies; inverse relationships were more consistently found in
      studies of fatal injury (77.4%) than in studies of non-fatal injury (58%).
      Approximately two-thirds of the studies (n=73, 61%) measured SES along a gradient
      and 59% used more than one measure of SES (n=70). Studies that used a gradient
      measure of SES and/or more than one measure of SES identified significant
      relationships more often. These findings were essentially equivalent to those of
      a similar 2002 review (Cubbin & Smith, 2002). CONCLUSIONS: There remains a need
      to improve measurement of SES in injury research. Public health training programs
      should include best practices for measurement of SES, which include: measuring
      SES along a gradient, selecting SES indicators based on the injury mechanism,
      using the smallest geographic region possible for area-level measures, using
      multiple indicators when possible, and using both individual and area-level
      measures as both contribute independently to injury risk. Area-level indicators
      of SES are not accurate estimates of individual-level SES. PRACTICAL
      APPLICATIONS: Injury researchers should measure SES along a gradient and
      incorporate individual and area-level SES measures that are appropriate to the
      injury outcome under study.

PMID- 29636171
TI  - Does company size matter? Validation of an integrative model of safety behavior
      across small and large construction companies.
AB  - INTRODUCTION: Previous safety climate studies primarily focused on either large
      construction companies or the construction industry as a whole, while little is
      known about whether company size has significant effects on workers'
      understanding of safety climate measures and relationships between safety climate
      factors and safety behavior. Thus, this study aims to: (a) test the measurement
      equivalence (ME) of a safety climate measure across workers from small and large
      companies; (b) investigate if company size alters the causal structure of the
      integrative model developed by Guo, Yiu, and Gonzalez (2016). METHOD: Data were
      collected from 253 construction workers in New Zealand using a safety climate
      measure. This study used multi-group confirmatory factor analyses (MCFA) to test
      the measurement equivalence of the safety climate measure and structure
      invariance of the integrative model. RESULTS: Results indicate that workers from
      small and large companies understood the safety climate measure in a similar
      manner. In addition, it was suggested that company size does not change the
      causal structure and mediational processes of the integrative model. CONCLUSIONS:
      Both measurement equivalence of the safety climate measure and structural
      invariance of the integrative model were supported by this study. Practical
      applications: Findings of this study provided strong support for a meaningful use
      of the safety climate measure across construction companies in different sizes.
      Safety behavior promotion strategies designed based on the integrative model may
      be well suited for both large and small companies.

PMID- 29636172
TI  - Characterization of fall patients: Does age matter?
AB  - INTRODUCTION: Evaluating age-specific fall characteristics is important for
      prevention programs. The aim was to characterize fallers who presented to our
      trauma center. We hypothesized that fall characteristics and outcomes would vary
      with age. METHODS: Data were retrospectively collected from the trauma registry
      and electronic medical records during January 1st, 2014-December 31st, 2015. Data
      were analyzed by Chi-square test with Yates' continuity correction and one-way
      ANOVA with Bonferroni's multiple comparisons test. RESULTS: There were 1541
      fallers, 814 (52.8%) were male. Ages ranged from 11 months to 100years. The
      admission rate was high at 86%, with an average hospital stay of 5.7days.
      Patients in the 0-18 and 19-45age groups spent significantly less time in the
      hospital (p<0.0001). Elderly patients had the highest average injury severity
      score (p<0.0001). However, the youngest patients required surgery more often
      (p=0.0004). The overall mortality rate was 3.6% and 52.8% were male. The
      mortality rate increased with age, from 0% for the 0-18 age group to 6.9% for
      patients >=65years of age. Remarkably, fallers in the 19-45 and 46-64age groups
      predominantly died from ground level falls even though the average fall height in
      these groups was the highest (p<0.0001). More fallers in the 19-45 and 46-64age
      groups tested positive for alcohol/drug use (p<0.0001). Middle-aged and elderly
      patients were more likely to be discharged to a skilled nursing or rehabilitation
      facility compared to younger patients who were discharged home. CONCLUSIONS AND
      PRACTICAL APPLICATIONS: Fall characteristics and outcomes varied with age. Data
      on age-specific characteristics, outcomes, and risk factors of falls will help in
      developing targeted interventions and may lead to better approaches to treat
      patients.

PMID- 29636173
TI  - Evaluating an intervention to improve belt fit for adult occupants.
AB  - INTRODUCTION: Previous laboratory studies have demonstrated that some drivers
      position their seat belts suboptimally. Specifically, the lap portion of the belt
      may be higher and farther forward relative to the pelvis than best practice, and
      the shoulder portion of the belt may be outboard or inboard of mid-shoulder. This
      study evaluated the performance of a video-based intervention for improving the
      belt fit obtained by drivers. METHOD: Twenty-nine adult drivers participated in
      this study. Belt fit was measured before and after the intervention in
      participants' vehicles and in a laboratory mockup. RESULTS: Data from both the in
      vehicle and laboratory belt measures found that 95% of participants sampled
      improved some aspect of lap belt fit. For the in-vehicle test conditions,
      participants who lowered the lap belt location (Z) after the intervention showed
      an improvement of 26 mm on average. Among those participants who shifted the
      horizontal lap belt location rearward (closer to the pelvis), an average
      improvement of 36 mm was observed. No significant differences were observed
      between baseline and post-intervention shoulder belt fit. CONCLUSIONS: The
      results provide preliminary evidence that an intervention improves driver belt
      fit. More research is needed to establish what aspects of this intervention
      affected behavior and how effective such an intervention is in the context of
      public health. PRACTICAL APPLICATIONS: These findings can help better inform
      intervention initiatives to improve occupant belt fit.

PMID- 29636174
TI  - Erratum to "Restricted Diversity of Antigen Binding Residues of Antibodies
      Revealed by Computational Alanine Scanning of 227 Antibody-Antigen Complexes" [J.
      Mol. Biol., 426, 2014, 3729-3743].

PMID- 29636176
TI  - Do relevant shear forces appear in isokinetic shoulder testing to be implemented
      in biomechanical models?
AB  - Isokinetic dynamometers measure joint torques about a single fixed rotational
      axis. Previous studies yet suggested that muscles produce both tangential and
      radial forces during a movement, so that the contact forces exerted to perform
      this movement are multidirectional. Then, isokinetic dynamometers might neglect
      the torque components about the two other Euclidean space axes. Our objective was
      to experimentally quantify the shear forces impact on the overall shoulder
      torque, by comparing the dynamometer torque to the torque computed from the
      contact forces at the hand and elbow. Ten healthy women performed isokinetic
      maximal internal/external concentric/eccentric shoulder rotation movements. The
      hand and elbow contact forces were measured using two six-axis force sensors. The
      main finding is that the contact forces at the hand were not purely tangential to
      the direction of the movement (effectiveness indexes from 0.26 +/- 0.25 to 0.54
      +/- 0.20), such that the resulting shoulder torque computed from the two force
      sensors was three-dimensional. Therefore, the flexion and abduction components of
      the shoulder torque measured by the isokinetic dynamometer were significantly
      underestimated (up to 94.9%). These findings suggest that musculoskeletal models
      parameters should not be estimated without accounting for the torques about the
      three space axes.

PMID- 29636177
TI  - [Effect of video-based education on anxiety and satisfaction of patients
      undergoing spinal anesthesia].
AB  - BACKGROUND: Providing sufficient information during a preanesthetic interview may
      help improve patient understanding and decrease anxiety related to spinal
      anesthesia. We investigated the effect of video-based education on anxiety and
      satisfaction in patients about to undergo spinal anesthesia. METHODS: A total of
      198 patients scheduled for minor elective surgery under spinal anesthesia were
      prospectively enrolled. The State-Trait Anxiety Inventory (State-Trait Anxiety
      Inventory/State and State-Trait Anxiety Inventory/Trait) questionnaires and
      visual analog scale were used to measure anxiety levels before the standard
      anesthesia evaluation was initiated. Then, 100 patients in Group 1 received
      written, verbal, and video-based education, whereas 98 patients in Group 2
      received only written and verbal instructions regarding spinal anesthesia. Then
      all participants completed the State-Trait Anxiety Inventory/State and visual
      analog scale to evaluate anxiety. Finally, a 5-point Likert scale was used to
      measure satisfaction during postoperative period. RESULTS: No differences were
      found in the State-Trait Anxiety Inventory/State, State-Trait Anxiety
      Inventory/Trait, or visual analog scale scores between the two groups before the
      information period. The State-Trait Anxiety Inventory/State scores evaluating
      anxiety during the post-information period were differed in both groups and they
      found as 36.5+/-10.0 in Group 1 and 39.6+/-8.6 in Group 2 (p=0.033). The 5-point
      Likert scale scores to measure satisfaction were stated as 4.5+/-0.6 in Group 1
      and 3.5+/-1.2 in Group 2 (p<0.001). CONCLUSIONS: Providing video-based
      information during the preanesthetic interview alleviated anxiety and increased
      satisfaction in patients undergoing spinal anesthesia.

PMID- 29636178
TI  - Improved separation with the intermittently pressed tubing of multilayer coil in
      type-I counter-current chromatography.
AB  - The intermittently pressed tubing was introduced in type-I counter-current
      chromatographic system as the separation column to improve the separation
      performance in the present study. The separations were performed with two
      different solvent systems composed of 1-butanol-acetic acid-water (4:1:5, v/v)
      (BAW) and hexane-ethyl acetate-methanol-0.1 M HCl (1:1:1:1, v/v) (HEMW) using
      dipeptides and DNP-amino acids as test samples, respectively. The chromatographic
      performance was evaluated in terms of retention of the stationary phase (Sf),
      theoretical plate (N) and peak resolution (Rs). In general, the type-I planetary
      motion with the multilayer coil of non-modified standard tubing can yield the
      best separation at a low revolution speed of 200 rpm with lower flow rate. The
      present results with intermittently pressed tubing indicated that the performance
      was also optimal at the revolution speed of 200 rpm where the lower flow rate was
      more beneficial to retention of stationary phase and resolution. In the
      moderately hydrophobic two-phase solvent system composed of hexane-ethyl acetate
      metanol-0.1 M hydrochloric acid (1:1:1:1, v/v), DNP-amino acids were separated
      with Rs at 1.67 and 1.47, respectively, with 12.66% of stationary phase retention
      at a flow rate of 0.25 ml/min. In the polar solvent system composed of 1-butanol
      acetic acid-water (4:1:5, v/v), dipeptide samples were resolved with Rs at 2.18
      and 18.75% of stationary phase retention at a flow rate of 0.25 ml/min. These
      results indicate that the present system substantially improves the separation
      efficiency of type-I counter-current chromatographic system.

PMID- 29636179
TI  - A biomechanical model for fibril recruitment: Evaluation in tendons and arteries.
AB  - Simulations of soft tissue mechanobiological behaviour are increasingly important
      for clinical prediction of aneurysm, tendinopathy and other disorders. Mechanical
      behaviour at low stretches is governed by fibril straightening, transitioning
      into load-bearing at recruitment stretch, resulting in a tissue stiffening
      effect. Previous investigations have suggested theoretical relationships between
      stress-stretch measurements and recruitment probability density function (PDF)
      but not derived these rigorously nor evaluated these experimentally. Other work
      has proposed image-based methods for measurement of recruitment but made use of
      arbitrary fibril critical straightness parameters. The aim of this work was to
      provide a sound theoretical basis for estimating recruitment PDF from stress
      stretch measurements and to evaluate this relationship using image-based methods,
      clearly motivating the choice of fibril critical straightness parameter in rat
      tail tendon and porcine artery. Rigorous derivation showed that the recruitment
      PDF may be estimated from the second stretch derivative of the first Piola
      Kirchoff tissue stress. Image-based fibril recruitment identified the fibril
      straightness parameter that maximised Pearson correlation coefficients (PCC) with
      estimated PDFs. Using these critical straightness parameters the new method for
      estimating recruitment PDF showed a PCC with image-based measures of 0.915 and
      0.933 for tendons and arteries respectively. This method may be used for accurate
      estimation of fibril recruitment PDF in mechanobiological simulation where fibril
      level mechanical parameters are important for predicting cell behaviour.

PMID- 29636180
TI  - Caffeine: A Not So Stiff Drink.

PMID- 29636183
TI  - Hydrophobic and superhydrophobic surfaces fabricated using atmospheric pressure
      cold plasma technology: A review.
AB  - Hydrophobic surfaces are often used to reduce wetting of surfaces by water. In
      particular, superhydrophobic surfaces are highly desired for several applications
      due to their exceptional properties such as self-cleaning, anti-icing, anti
      friction and others. Such surfaces can be prepared via numerous methods including
      plasma technology, a dry technique with low environmental impact. Atmospheric
      pressure plasma (APP) has recently attracted significant attention as lower-cost
      alternative to low-pressure plasmas, and as a candidate for continuous rather
      than batch processing. Although there are many reviews on water-repellent
      surfaces, and a few reviews on APP technology, there are hardly any review works
      on APP processing for hydrophobic and superhydrohobic surface fabrication, a
      topic of high importance in nanotechnology and interface science. Herein, we
      critically review the advances on hydrophobic and superhydrophobic surface
      fabrication using APP technology, trying also to give some perspectives in the
      field. After a short introduction to superhydrophobicity of nanostructured
      surfaces and to APPs we focus this review on three different aspects: (1) The
      atmospheric plasma reactor technology used for fabrication of (super)hydrophobic
      surfaces. (2) The APP process for hydrophobic surface preparation. The
      hydrophobic surface preparation processes are categorized methodologically as: a)
      activation, b) grafting, c) polymerization, d) roughening and hydrophobization.
      Each category includes subcategories related to different precursors used. (3)
      One of the most important sections of this review concerns superhydrophobic
      surfaces fabricated using APP. These are methodologically characterized as
      follows: a) single step processes where micro-nano textured topography and low
      surface energy coating are created at the same time, or b) multiple step
      processes, where these steps occur sequentially in or out of the plasma. We end
      the review with some perspectives in the field. We aspire to address scientists,
      who will get involved in the fields of (super)hydrophobicity and/or in
      atmospheric pressure plasma processing.

PMID- 29636182
TI  - Soybean-derived recombinant human epidermal growth factor protects against
      experimental necrotizing enterocolitis.
AB  - BACKGROUND: Epidermal Growth Factor (EGF) reduces necrotizing enterocolitis
      (NEC). However, its high cost virtually prohibits clinical use. To reduce cost,
      soybean expressing human EGF was developed. Here we report effectiveness of
      soybean-derived EGF in experimental NEC. METHODS: Newborn rats were subjected to
      the NEC-inducing regimen of formula feeding and hypoxia. Formula was supplemented
      with extract from EGF-expressing or empty soybeans. NEC pathology was determined
      microscopically. Localization of tight junction proteins JAM-A and ZO-1 was
      examined by immunofluorescence and levels of mucosal COX-2 and iNOS mRNAs by real
      time PCR. RESULTS: Soybean extract amounts corresponding to 150MUg/kg/day EGF
      caused considerable mortality, whereas those corresponding to 75MUg/kg/day EGF
      were well tolerated. There was no significant difference in NEC scores between
      animals fed plain formula and formula supplemented with empty soybean extract.
      Soybean-EGF-supplemented formula at 75MUg/kg/day EGF significantly decreased NEC,
      attenuated dissociation of JAM-A and ZO-1 proteins from tight junctions, and
      reduced intestinal expression of COX-2 and iNOS mRNAs. CONCLUSION:
      Supplementation with soybean-expressed EGF significantly decreased NEC in the rat
      model. Soybean-expressed EGF may provide an economical solution for EGF
      administration and prophylaxis of clinical NEC.

PMID- 29636181
TI  - Antigen processing and presentation in HIV infection.
AB  - The presentation of virus-derived peptides by MHC molecules constitutes the
      earliest signals for immune recognition by T cells. In HIV infection, immune
      responses elicited during infection do not enable to clear infection and
      correlates of immune protection are not well defined. Here we review features of
      antigen processing and presentation specific to HIV, analyze how HIV has adapted
      to the antigen processing machinery and discuss how advances in biochemical and
      computational protein degradation analyses and in immunopeptidome definition may
      help identify targets for efficient immune clearance and vaccine immunogen
      design.

PMID- 29636184
TI  - Pre-injury depression and anxiety in patients with orthopedic trauma and their
      treatment.
AB  - PURPOSE: Depressive symptoms have a known negative impact on outcomes following
      musculoskeletal injury. This study determined the pre-injury prevalence of
      psychiatric diagnoses of depression and anxiety, medication lapses and
      psychiatric consult services among patients admitted for orthopaedic trauma.
      METHODS: This is a retrospective study of data from our Level-1 trauma center.
      Patients admitted to the orthopaedic trauma service during 2010-2015 were
      included (N = 4053). Demographics, Injury Severity Scores (ISS), mental health
      diagnoses, psychotropic medications, medication type and delay, psychiatric
      consultation use, intensive care unit (ICU) stay and total hospital length of
      stay (LOS) were abstracted from medical records and the institutional trauma
      registry. RESULTS: The 12-month prevalence of a major depressive episode is 6.6%
      8.6% in adults in the United States. In our database, only 152/4053 (3.8%) of the
      patients had documented medical history of depression (80%) or anxiety (30%), and
      these patients had a 32% longer LOS (p < 0.016). Nearly two-thirds of patients
      who used psychotropic medications prior to injury experienced a delay in
      receiving these medications in the hospital (median = 1.0 day, range 0-14 days).
      Sixteen percent of patients also received a new psychotropic medication while
      hospitalized: an antipsychotic (8/16 patients, to treat delirium), an anxiolytic
      (3/16 patients for acute anxiety), or an antidepressant (1/16). Among patients
      with depression or anxiety, 16.7% received a psychiatric consult. Patients with
      psychiatric consults had higher ISS, were more likely to have longer ICU LOS and
      had longer hospital LOS than those without consults (all p < 0.05). CONCLUSION:
      The prevalence of depression and anxiety is grossly under-reported in our
      registry compared to national prevalence data. Patients with pre-existing disease
      had longer LOS and a higher rate of extended ICU care. Further studies are needed
      to characterize the true prevalence of disease in this patient population and its
      effect on patient outcomes after traumatic orthopaedic injury.

PMID- 29636185
TI  - Choosing an optimal implant fixation for basicervical femoral neck fractures.

PMID- 29636186
TI  - Status of faecal pollution in ports: A basin-wide investigation in the Adriatic
      Sea.
AB  - Ports are subject to a variety of anthropogenic impacts, and there is mounting
      evidence of faecal contamination through several routes. Yet, little is known
      about pollution in ports by faecal indicator bacteria (FIB). FIB spatio-temporal
      dynamics were assessed in 12 ports of the Adriatic Sea, a semi-enclosed basin
      under strong anthropogenic pressure, and their relationships with environmental
      variables were explored to gain insight into pollution sources. FIB were abundant
      in ports, often more so than in adjacent areas; their abundance patterns were
      related to salinity, oxygen, and nutrient levels. In addition, a molecular
      method, quantitative (q)PCR, was used to quantify FIB. qPCR enabled faster FIB
      determination and water quality monitoring that culture-based methods. These data
      provide robust baseline evidence of faecal contamination in ports and can be used
      to improve the management of routine port activities (dredging and ballast water
      exchange), having potential to spread pathogens in the sea.

PMID- 29636187
TI  - Reply to: "A measure of alcohol consumption in late adolescence associated with
      liver disease after 39 years of follow-up is insufficient to guide alcohol safe
      limits".

PMID- 29636188
TI  - Staging nodal metastases in nasopharyngeal carcinoma: which method should be used
      to measure nodal dimension on MRI?
AB  - AIM: To investigate four methods to measure the maximum dimension (MD) of
      metastatic neck nodes and correlate with clinical outcome in nasopharyngeal
      carcinoma (NPC). MATERIALS AND METHODS: Magnetic resonance imaging (MRI)
      examinations of 712 NPC patients were analysed. MD measurements using methods 1,
      2, 3, and 4 were obtained from a single node in the axial plane; a single node in
      the axial/coronal plane; a single and/or confluent nodes in the axial/coronal
      plane; and a single and/or confluent and/or contiguous nodes in the axial/coronal
      plane, respectively. MDs obtained from the four methods were correlated with
      nodal volume (NV) using Pearson's correlation test. MDs obtained from the four
      methods, T and N stages, age, gender, and treatment were correlated with overall
      survival (OS), disease-specific survival (DSS), distant metastases free survival
      (DMFS), and regional relapse-free survival (RRFS) using cox regression. RESULTS:
      Method 4 (R: 0.84) had the strongest correlation with NV followed by method 3 (R:
      0.77), method 2 (R: 0.70) and method 1(R: 0.69). Method 4 was the only
      independent nodal measurement of OS, DSS, and DMFS (p-values = 0.008, <0.001 and
      <0.001, respectively). None of the MD methods was an independent measurement of
      RRFS. CONCLUSIONS: The best method to obtain the MD for staging incorporates not
      only single and confluent, but also contiguous metastatic nodes measured in the
      plane with the MD.

PMID- 29636189
TI  - Reflections of a Biomedical Scientist on Four Continents in Interdisciplinary
      Research.

PMID- 29636190
TI  - A heart valve is no stronger than its weakest link: The need to improve
      durability of pericardial leaflets.

PMID- 29636191
TI  - Energized lung resections.

PMID- 29636192
TI  - Re: Letter to the editor of public health in response to 'Access to treatment
      with controlled medicines rationale and recommendations for neutral, respectful,
      and precise language'.

PMID- 29636193
TI  - Acute coronary syndrome in a young woman: The search of systemic arterial
      involvement.

PMID- 29636194
TI  - Bites after a trip to Brazil.

PMID- 29636195
TI  - Dermatomyositis-like Eruption in a Woman Treated With Hydroxyurea.

PMID- 29636196
TI  - RF-Topical Rapamycin as an Adjuvant to Laser Treatment in Capillary
      Malformations.

PMID- 29636197
TI  - Angio-OCT findings in juvenile X-linked retinoschisis.

PMID- 29636198
TI  - Determination of risk factors for burn mortality based on a regional population
      study in Taiwan.
AB  - BACKGROUND: Burns are not only major personal catastrophic events but also
      constitute a national health problem due to its associated morbidity,
      rehabilitation, mortality and high cost medical services. Advances in care and
      treatment have increased survival from major burn injury. However, information on
      the epidemiology and risk factors of burn mortality in Taiwan is limited. The
      study aim was to determine the nationwide epidemiological characteristics,
      trends, and mortality risk factors of burn inpatients in Taiwan. METHODS: This
      nationwide population-based study evaluated data retrieved from the Taiwan
      National Health Insurance database. Patients hospitalized for burns (ICD-9-CM
      codes 940-949) between 2003 and 2013 were identified from hospitalization
      records. RESULTS: A total of 73,774 patients were included. The data showed
      increases in age, revised Baux score, and Charlson Comorbidity Index during the
      study period, but it was also accompanied by a continuing decrease in burn
      incidence and a significant shortening of the length of hospital stay. The
      average in-hospital mortality was 17.5/1000 in 2003 and 12.2/1000 in 2013 but did
      not showed significant change. Male gender, older age, higher Charlson
      Comorbidity Index, presence of inhalation injury, large total burn surface area
      (TBSA), and higher revised Baux score were significant predictors of mortality.
      CONCLUSION: Population-based burn epidemiology data demonstrated ongoing
      improvement in hospital care during the past decade. Male gender, older age,
      higher Charlson Comorbidity Index, presence of inhalation injury, large TBSA, and
      higher revised Baux score were significant predictors of mortality.

PMID- 29636199
TI  - Estimation of sex and stature using anthropometry of the upper extremity in an
      Australian population.
AB  - Stature and a further 8 anthropometric dimensions were recorded from the arms and
      hands of a sample of 96 staff and students from the Australian National
      University and The University of Newcastle, Australia. These dimensions were used
      to create simple and multiple logistic regression models for sex estimation and
      simple and multiple linear regression equations for stature estimation of a
      contemporary Australian population. Overall sex classification accuracies using
      the models created were comparable to similar studies. The stature estimation
      models achieved standard errors of estimates (SEE) which were comparable to and
      in many cases lower than those achieved in similar research. Generic, non sex
      specific models achieved similar SEEs and R2 values to the sex-specific models
      indicating stature may be accurately estimated when sex is unknown.

PMID- 29636200
TI  - GPR and ERT detection and characterization of a mass burial, Spanish Civil War,
      Northern Spain.
AB  - Around 27,000 people were killed in the province of Asturias during the Spanish
      Civil War, with several thousands killed after the war ended. There are currently
      over 2,000 known mass burial locations throughout Spain, but many more are
      unknown. Geophysics is a useful tool employed to help in the active attempts to
      document and improve knowledge about victims from this conflict. This paper
      details a non-invasive study of the Cementerio de El Salvador, in the city of
      Oviedo, Northern Spain. Part of the cemetery contains a known mass burial with
      approximately 1,300 individuals from the Spanish Civil War and post-war
      repression eras. Multi-frequency near-surface geophysical techniques were
      undertaken, after permission, to enhance knowledge about which, if any,
      techniques should be used to detect, delineate and analyse such mass graves.
      Multi-frequency (250MHz and 500MHz) ground-penetrating radar surveys were
      acquired together with 2D and 3D Electrical Resistivity Tomography datasets. The
      results have established the limits of the mass grave and improve the knowledge
      of the internal mass grave structure. The paper also shows the importance of
      considering the climatic conditions during data acquisition. This has important
      implications for the successful detection of recent historical mass burials using
      near-surface geophysics.

PMID- 29636201
TI  - Therapeutic adherence: The elephant in the room.

PMID- 29636202
TI  - Drug-induced life-threatening arrhythmias and sudden cardiac death: A clinical
      perspective of long QT, short QT and Brugada syndromes.
AB  - Sudden cardiac death is a major public health challenge, which can be caused by
      genetic or acquired structural or electrophysiological abnormalities. These
      abnormalities include hereditary channelopathies: long QT, short QT and Brugada
      syndromes. These syndromes are a notable concern, particularly in young people,
      due to their high propensity for severe ventricular arrhythmias and sudden
      cardiac death. Current evidence suggests the involvement of an increasing number
      of drugs in acquired forms of long QT and Brugada syndromes. However, drug
      induced short QT syndrome is still a rarely reported condition. Therefore, there
      has been speculation on its clinical significance, since few fatal arrhythmias
      and sudden cardiac death cases have been described so far. Drug-induced
      proarrhythmia is a growing challenge for physicians, regulatory agencies and the
      pharmaceutical industry. Physicians should weigh the risks of potentially fatal
      outcomes against the therapeutic benefits, when making decisions about drug
      prescriptions. Growing concerns about its safety and the need for more accurate
      predictive models for drug-induced fatal outcomes justify further research in
      these fields. The aim of this article is to comprehensively and critically review
      the recently published evidence with regard to drug-induced life-threatening
      arrhythmias and sudden cardiac death. This article will take into account the
      provision of data to physicians that are useful in the identification of the
      culprit drugs, and thus, contribute to the prompt recognition and management of
      these serious clinical conditions.

PMID- 29636203
TI  - Acquired fistula from left anterior descending artery to coronary sinus: An
      unusual finding during percutaneous coronary intervention.

PMID- 29636204
TI  - Surgical outcomes in the treatment of temporal bone cerebrospinal fluid leak: A
      systematic review.

PMID- 29636205
TI  - Comparison of functional outcomes after total thyroidectomy and completion
      thyroidectomy: Hypoparathyroidism and postoperative complications.
AB  - OBJECTIVE: This study aimed to investigate differences in functional outcomes of
      postoperative complications and hypoparathyroidism between patients who underwent
      completion thyroidectomy (CT) after thyroid lobectomy or total thyroidectomy (TT)
      as an initial treatment. MATERIALS AND METHODS: We retrospectively analyzed the
      differences of functional outcomes after completion thyroidectomy and total
      thyroidectomy without lymph node dissection. We reviewed the medical records of
      396 patients who underwent CT or TT for thyroid disease at Korea University Guro
      Hospital from March 2002 to August 2016. RESULTS: Of the 396 patients, 32
      underwent CT and 364 underwent TT. There were 72 male patients and 324 female
      patients. Transient hypoparathyroidism was observed in 4 (9.4%) of the CT
      patients and 97 (26.6%) of the TT patients, with a statistically significant
      difference (p=0.031). Permanent hypoparathyroidism was observed in 1 patient
      (3.1%) in the CT group and in 13 patients (3.6%) in the TT group, which was not
      significantly different. There were no significant differences in the
      postoperative complication of temporary recurrent laryngeal nerve injury, wound
      infection, and hematoma between two patients group. CONCLUSION: The incidence of
      transient hypoparathyroidism in CT patients was significantly lower than in TT
      patients. These safety and functional superiority of CT should be considered when
      determining the scope and extent of operation in patients requiring surgery for
      thyroid disease.

PMID- 29636206
TI  - Continuous improvement in hand therapy: Lean and the improvement Kata mindset.

PMID- 29636207
TI  - Long-term home non-invasive positive pressure ventilation in children: Results
      from a single center in Japan.
AB  - BACKGROUND: Non-invasive positive pressure ventilation (NPPV) in children has
      recently increased worldwide and is used not only for neuromuscular diseases but
      for various other diseases. However, there have been few observational studies on
      long-term NPPV in children in Japan. METHODS: Based on medical records, we
      retrospectively evaluated patients aged <=20 years who were initiated long-term
      NPPV at our hospital from January 2001 to December 2015. RESULTS: A total of 53
      patients on long-term NPPV were identified; 38 (72%) had severe motor and
      intellectual disabilities (SMID). Compared to those with non-neuromuscular
      diseases, those with neuromuscular diseases had significantly more planned
      initiations and less frequent use of oxygen. Regarding patient outcome, 34
      patients continued NPPV (64%), and there were three discontinues (6%), seven
      tracheostomies (13%), and nine deaths (17%). The continuation rate was high among
      those with neuromuscular disorders (15/19 cases, 79%) and that of tracheotomy was
      high in those with metabolic/degenerative diseases (3/9 cases, 33%). Ten patients
      transitioned to adult care, accounting for 29% of the 34 continuing patients.
      CONCLUSION: This is the first observational study on long-term NPPV use in
      children in Japan that examined outcomes in patients with a range of disorders.
      The initiation situation, management, and outcomes differed between patients with
      neuromuscular and non-neuronal muscular diseases. Long-term use of NPPV is
      possible in many cases, including children with SMID, but can be challenging to
      continue in patients with progressive diseases such as metabolic/degenerative
      diseases. Careful discussions regarding the management of each patient are
      necessary.

PMID- 29636208
TI  - Contribution of collagen and connective tissue to cooked meat toughness; some
      paradigms reviewed.
AB  - Variations in the quantity and thermal stability of collagen in intramuscular
      connective tissue (IMCT) play a role in variations in cooked meat tenderness.
      This review is focussed on sources of variability, especially in the perimysial
      IMCT, and challenges some of the accepted ideas about its denaturation behaviour,
      its contribution to cooking shrinkage at high temperatures and the concept of
      IMCT as an immutable "background toughness". IMCT dominates the shear strength of
      raw and lightly cooked muscle, but at cooking temperatures of 70-80 degrees  its
      contribution is smaller than the myofibrillar component. The thermal denaturation
      temperature of IMCT collagen given by differential scanning calorimetry at fast
      heating rates is usually in the range of 62-67  degrees C, but collagen
      denaturation is a multistep, non-equilibrium process that is highly heating-rate
      dependent and can occur at 55-60  degrees C in slow heating regimes, such as slow
      roasting or sous-vide cooking. Although it is commonly assumed that collagen
      shrinkage drives shrinkage of meat and greater cooking losses above 65  degrees
      C, an examination of currently available information suggested that there is no
      evidence to support this idea. The amount and thermal stability of IMCT collagen
      can be varied by factors manipulating growth rate, and a recent model of these
      effects is discussed. The characteristics of the thermally-stable fraction of
      IMCT collagen as the most important component influencing the connective tissue
      contribution to cooked meat toughness and the need for future work investigating
      mechanisms to degrade or turnover this specific fraction is suggested.

PMID- 29636209
TI  - Sensitivity of spermatogonia to irradiation varies with age in pre-pubertal ram
      lambs.
AB  - Although germ cells from donor rams transplanted into irradiated recipient testes
      have produced donor derived offspring, efficiency is low. Further optimization of
      recipient irradiation protocols will add precision to the depletion of recipient
      spermatogonia prior to germ cell transplant. Three irradiation doses (9,12,15 Gy)
      were administered to ram lambs aged 14 weeks (Group 1) and 20 weeks (Group 2),
      then testicular biopsies were collected 1, 2 and 3 months after irradiation. At 1
      month after irradiation of Group 1, only the largest dose (15 Gy) reduced
      spermatogonia numbers below 10% of non-irradiated controls, whereas in Group 2
      lambs, each irradiation dose reduced spermatogonia below 10% of controls. In both
      Groups, fewer differentiated germ cells were present in seminiferous tubules
      compared to controls. At 2 months after irradiation, spermatogonia numbers in
      both Groups increased more than sixfold to be similar to controls, whereas fewer
      differentiated germ cells were present in the tubules of both Groups. At 3 months
      in Group 1, each irradiation dose reduced spermatogonia numbers to <30% of
      controls and fewer tubules contained differentiated germ cells. Lesser expression
      of spermatogonial genes, VASA and UCHL-1, was observed in the 15 Gy group. In
      Group 2, only 12 Gy treated tubules contained fewer spermatogonia. Knowledge of
      these subtle differences between age groups in the effect of irradiation doses on
      spermatogonia or differentiated germ cell numbers and the duration of recovery of
      spermatogonia numbers after irradiation will aid the timing of germ cell
      transplants into prepubertal recipient lambs.

PMID- 29636210
TI  - Uteroplacental secretion of progesterone and estradiol-17beta in an ovine model
      of intrauterine growth restriction.
AB  - Using a mid to late gestation model of intrauterine growth restriction,
      uteroplacental secretion of progesterone and estradiol-17beta were examined. From
      day 50 to 130 of gestation, 31 ewe lambs were allocated to receive 100% (ADQ) or
      60% (RES) of nutrient requirements. At day 130, umbilical and uterine artery
      blood flows were determined and blood samples were collected from maternal
      saphenous artery, gravid uterine vein, umbilical vein, and umbilical artery.
      Uteroplacental secretion of progesterone was increased in RES compared to ADQ fed
      dams. There was a net secretion and net metabolism of estradiol-17beta in RES,
      and ADQ fed dams, respectively. In relation to steroid synthesis, cotyledonary
      abundance of steroidogenic acute regulatory protein was greater in RES compared
      with ADQ fed dams, while abundance of aromatase was not different between dietary
      treatments. Caruncular aldo-keto reductase 1C abundance was less in RES compared
      to ADQ fed dams. The increase in progesterone secretion, therefore, is due in
      part to an increase in synthesis and a decrease in placental catabolism.
      Caruncular cytochrome P450 3A, which catalyzes the conversion of estrogens to
      catechol-estrogens, was in lesser abundance in RES compared to ADQ fed dams.
      Opposite responses in estradiol-17beta uteroplacental secretion compared with
      metabolism may be mediated through placental estrogen metabolism via cytochrome
      P450 enzymes.

PMID- 29636211
TI  - Primary mesothelial cyst of the spleen as an uncommon cause of dyspepsia: A case
      report.

PMID- 29636213
TI  - Conformation Polymorphism of Polyglutamine Proteins.
AB  - Expanded polyglutamine (polyQ) stretches within endogenous proteins cause at
      least nine human diseases. The structural basis of polyQ pathogenesis is the key
      to understanding fundamental mechanisms of these diseases, but it remains unclear
      and controversial due to a lack of polyQ protein structures at the single-atom
      level. Various hypotheses have been proposed to explain the structure
      cytotoxicity relationship of pathogenic proteins with polyQ expansion, largely
      based on indirect evidence. Here we review these hypotheses and their supporting
      evidence, along with additional insights from recent structural biology and
      chemical biology studies, with a focus on Huntingtin (HTT), the most extensively
      studied polyQ disease protein. Lastly, we propose potential novel strategies that
      may further clarify the conformation-cytotoxicity relationship of polyQ proteins.

PMID- 29636212
TI  - Structural Basis of Arrestin-Dependent Signal Transduction.
AB  - Arrestins are a small family of proteins with four isoforms in humans.
      Remarkably, two arrestins regulate signaling from >800 G protein-coupled
      receptors (GPCRs) or nonreceptor activators by simultaneously binding an
      activator and one out of hundreds of other signaling proteins. When arrestins are
      bound to GPCRs or other activators, the affinity for these signaling partners
      changes. Thus, it is proposed that an activator alters arrestin's ability to
      transduce a signal. The comparison of all available arrestin structures
      identifies several common conformational rearrangements associated with
      activation. In particular, it identifies elements that are directly involved in
      binding to GPCRs or other activators, elements that likely engage distinct
      downstream effectors, and elements that likely link the activator-binding sites
      with the effector-binding sites.

PMID- 29636214
TI  - Patho-physiological evaluation of Duranta erecta for the treatment of
      urolithiasis.
AB  - BACKGROUND: Urolithiasis is the third common disorder of the urinary system
      affecting 10-15% of the general population. In recent years, search for new
      antilithiatic drugs from natural sources has assumed greater importance.
      OBJECTIVES: This study was performed to investigate the anti-urolithiatic
      activity of methanolic extract of Duranta erecta leaves by in vitro and in vivo
      analysis. MATERIALS AND METHODS: The study was designed to determine presence of
      phytochemicals in D. erecta, its yield in percentage, antioxidant activity
      against 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and anti-microbial property against
      few bacteria. In vitro analysis was carried out study anti-urolithiatic property
      of D. erecta by nucleation assay and synthetic urine assay for inhibition of
      calcium oxalate and calcium oxalate monohydrate crystals formation. An in vivo
      experiment was performed on Wistar rats for confirmation of anti-urolithiatic
      property of D. erecta in animal model. RESULTS: D. erecta has the presence of
      primary and secondary metabolites like glycoside, saponins, sterols, flavonoids,
      phenols, tannins, alkaloids, carbohydrates and proteins. Methanolic extract of D.
      erecta gave a very good yield (60%). D. erecta proved its antioxidant potential
      by 93.51% inhibition of DPPH radical at a concentration of 1000 MUg/mL where
      ascorbic showed 94.71% of DPPH radical at the same concentration. In vitro tests
      like nucleation assay and synthetic urine assay showed that D. erecta inhibits
      formation of calcium oxalate and calcium oxalate monohydrate crystals. It also
      showed the anti-microbial property by formation of zone of inhibition against few
      bacteria. An in vivo experiment on Wistar rat animal model confirmed the anti
      urolithiatic property of D. erecta L. leaves extract. CONCLUSIONS: Based on the
      results, we reported that D. erecta may treat calcium oxalate crystal deposition
      in the kidney by preventing hyperoxaluria-induced peroxidative damage to the
      renal tubular membrane surface (lipid peroxidation). It has anti-microbial
      potential so it may also inhibit the secondary bacterial infection in kidney.
      Based on the data, it can be concluded that this herb can be used as a potential
      anti-urolithiasis agent for kidney stone removal.

PMID- 29636215
TI  - Small intestinal bacterial overgrowth in Parkinson's disease: Tribulations of a
      trial.

PMID- 29636216
TI  - Conversion of sulfur compounds and microbial community in anaerobic treatment of
      fish and pork waste.
AB  - Volatile sulfur compounds (VSCs) are not only the main source of malodor in
      anaerobic treatment of organic waste, but also pose a threat to human health. In
      this study, VSCs production and microbial community was investigated during the
      anaerobic degradation of fish and pork waste. The results showed that after the
      operation of 245 days, 94.5% and 76.2% of sulfur compounds in the fish and pork
      waste was converted into VSCs. Among the detected VSCs including H2S, carbon
      disulfide, methanethiol, ethanethiol, dimethyl sulfide, dimethyl disulfide and
      dimethyl trisulfide, methanethiol was the major component with the maximum
      concentration of 4.54% and 3.28% in the fish and pork waste, respectively. The
      conversion of sulfur compounds including total sulfur, SO42--S, S2-, methionine
      and cysteine followed the first-order kinetics. Miseq sequencing analysis showed
      that Acinetobacter, Clostridium, Proteus, Thiobacillus, Hyphomicrobium and
      Pseudomonas were the main known sulfur-metabolizing microorganisms in the fish
      and pork waste. The C/N value had most significant influence on the microbial
      community in the fish and pork waste. A main conversion of sulfur compounds with
      CH3SH as the key intermediate was firstly hypothesized during the anaerobic
      degradation of fish and pork waste. These findings are helpful to understand the
      conversion of sulfur compounds and to develop techniques to control ordor
      pollution in the anaerobic treatment of organic waste.

PMID- 29636217
TI  - Methanosarcina plays a main role during methanogenesis of high-solids food waste
      and cardboard.
AB  - Anaerobic digestion of food waste is a complex process often hindered by high
      concentrations of volatile fatty acids and ammonia. Methanogenic archaea are more
      sensitive to these inhibitors than bacteria and thus the structure of their
      community is critical to avoid reactor acidification. In this study, the
      performances of three different inocula were compared using batch digestion tests
      of food waste and cardboard mixtures. Particular attention was paid to the
      archaeal communities in the inocula and after digestion. While the tests started
      with inocula rich in Methanosarcina led to efficient methane production, VFAs
      accumulated in the reactors where inocula initially were poor in this archaea and
      no methane was produced. In addition, higher substrate loads were tolerated when
      greater proportions of Methanosarcina were initially present in the inoculum.
      Independently of the inoculum origin, Methanosarcina were the dominant
      methanogens in the digestates from the experiments that efficiently produced
      methane. These results suggest that the initial archaeal composition of the
      inoculum is crucial during reactor start-up to achieve stable anaerobic digestion
      at high concentrations of ammonia and organic acids.

PMID- 29636218
TI  - Discovery of {4-[4,9-bis(ethyloxy)-1-oxo-1,3-dihydro-2H-benzo[f]isoindol-2-yl]-2
      fluorophenyl}acetic acid (GSK726701A), a novel EP4 receptor partial agonist for
      the treatment of pain.
AB  - A novel series of EP4 agonists and antagonists have been identified, and then
      used to validate their potential in the treatment of inflammatory pain. This
      paper describes these novel ligands and their activity within a number of pre
      clinical models of pain, ultimately leading to the identification of the EP4
      partial agonist GSK726701A.

PMID- 29636219
TI  - Divergent synthesis of thapsigargin analogs.
AB  - Thapsigargin (3) is a potent inhibitor of the SERCA-pump protein, with potential
      for application in a variety of medicinal areas. The efficient and scalable
      syntheses of thapsigargin (3) and nortrilobolide (2) have been disclosed
      previously. To demonstrate the modularity of the previous routes, three natural
      products (compounds 6, 13, 15) and four analogs (compounds 17-20) have been
      divergently prepared from a common building block featuring varied acyl chains at
      the C2, C3, and C8 positions. Biological tests revealed that all of the compounds
      prepared displayed promising activity profiles.

PMID- 29636221
TI  - Early predictors of clinical and mental outcome in tuberous sclerosis complex: A
      prospective study.
AB  - AIM: We aimed to identify early predictors of intractable epilepsy, intellectual
      disability (ID) and autism spectrum disorders (ASD) in the cohort of TSC patients
      initially diagnosed with cardiac rhabdomyomas (CR). METHOD: Over the period of
      twelve years we prospectively obtained clinical, neuropsychological,
      electrophysiological and neuroimaging data in a group of 22 TSC patients (9
      females, 13 males) with the pre/perinatal diagnosis of CR, included to the study
      at the time of diagnosis. Afterwards, we statistically determined variables
      associated with ID, ASD and intractable epilepsy. RESULTS: Development of ID was
      predicted by severe epilepsy (a higher number of anti-epileptic drugs used), a
      higher number of dysplastic lesions on MRI, and abnormal background activity on
      EEG (p < 0.05). Predictors of ASD included early developmental delay, abnormal
      background activity on EEG at the end of follow-up and a higher number of areas
      with dysplastic features on MRI (p < 0.05). Intractable epilepsy was associated
      with a higher number of areas with dysplastic features on MRI, ID and with TSC2
      genotype. CONCLUSION: Adverse mental and clinical outcome was associated with
      intractable epilepsy and the severe anatomical brain involvement; therefore, our
      centre developed a tailored protocol for early identification of TSC patients at
      a higher risk of developing intractable epilepsy with its deleterious effect on
      cognitive outcome.

PMID- 29636222
TI  - [Short-term resolution of B-lines in thoracic ultrasound in acute pulmonary
      oedema after treatment].

PMID- 29636220
TI  - Investigating small molecules to inhibit germinal center kinase-like kinase
      (GLK/MAP4K3) upstream of PKCtheta phosphorylation: Potential therapy to modulate
      T cell dependent immunity.
AB  - Germinal center kinase-like kinase (GLK, also known as MAP4K3) has been
      hypothesized to have an effect on key cellular activities, including inflammatory
      responses. GLK is required for activation of protein kinase C-theta (PKCtheta) in
      T cells. Controlling the activity of T helper cell responses could be valuable
      for the treatment of autoimmune diseases. This approach circumvents previous
      unsuccessful approaches to target PKCtheta directly. The use of structure based
      drug design, aided by the first crystal structure of GLK, led to the discovery of
      several inhibitors that demonstrate potent inhibition of GLK biochemically and in
      relevant cell lines.

PMID- 29636223
TI  - 2-Aminoquinazolin-4(3H)-one based plasmepsin inhibitors with improved
      hydrophilicity and selectivity.
AB  - 2-Aminoquinazolin-4(3H)-ones were previously discovered as perspective leads for
      antimalarial drug development targeting the plasmepsins. Here we report the lead
      optimization studies with the aim to reduce inhibitor lipophilicity and increase
      selectivity versus the human aspartic protease Cathepsin D. Exploiting the
      solvent exposed area of the enzyme provides an option to install polar groups
      (R1) the 5-position of 2-aminoquinazolin-4(3H)-one to inhibitors such as
      carboxylic acid without scarifying enzymatic potency. Moreover, introduction of
      R1 substituents increased selectivity factors of compounds in this series up to
      100-fold for Plm II, IV vs CatD inhibition. The introduction of flap pocket
      substituent (R2) at 7-postion of 2-aminoquinazolin-4(3H)-one allows to remove Ph
      group from THF ring without notably impairing Plm inhibitory potency. Based on
      these findings, inhibitors were developed, which show Plm II and IV inhibitory
      potency in low nanomolar range and remarkable selectivity against Cathepsin D
      along with decreased lipophilicity and increased solubility.

PMID- 29636224
TI  - Prohibition, regulation or laissez faire: The policy trade-offs of cannabis
      policy.
AB  - Trade-offs are central to the cannabis policy debate. Prohibition and strict
      regulation may help reduce the physical, mental and social harms of cannabis
      consumption, but at the cost of increasing the harms from illegal markets and
      reducing consumption benefits. An economic model clarifies how these costs and
      benefits relate to policy and connects them to observable prices and tax-levels
      given the assumptions of the analysis. These model- based arguments are related
      to the ongoing academic policy debate. While some arguments from this literature
      modify the interpretation of the model (e.g., due to dependence, cognitive biases
      and market structure), the literature often fails to appropriately account for
      the magnitude of the policy costs and benefits identified. Taking various caveats
      into account, the framework indicates that a strict regulation would likely be
      preferable to prohibition given current estimates of excess harms (externalities
      and internalities) from cannabis use. While cannabis prohibition appears
      difficult to justify within an economic regulatory framework, risks from industry
      influence, policy ratchet effects, and human "decision-making flaws" speak to the
      need for caution and strong regulation when implementing legal regimes.

PMID- 29636225
TI  - NDUFA4 (Renamed COXFA4) Is a Cytochrome-c Oxidase Subunit.
AB  - Groundbreaking work by Kadenbach and colleagues in the 1980s revealed the
      presence of 13 subunits in the mammalian mitochondrial cytochrome-c oxidase (COX;
      Complex IV). This observation stood the test of time until 2012 when it was
      demonstrated that NDUFA4, a polypeptide previously attributed to mitochondrial
      Complex I, was a 14th subunit of COX. In his recent opinion article, Kadenbach
      argued that NDUFA4 is not a subunit of COX. However, based on the findings that
      NDUFA4 deficiency results in a severe loss of COX activity and that NDUFA4
      represents a stoichiometric component of the individual COX complex, we reason
      that NDUFA4 is a bona fide COX subunit and propose renaming it as COX subunit FA4
      (COXFA4).

PMID- 29636226
TI  - Analysis of results of revision surgery of soft tissue sarcoma margins.

PMID- 29636227
TI  - Lumbar arthrodesis infection by multi-resistant Klebsiella pneumoniae,
      successfully treated with implant retention and ceftazidime/avibactam.
AB  - There are increasingly more patients with prosthetic implants (orthopaedic
      prostheses, lumbar instruments, osteosynthesis material). In the last decade,
      infections caused by carbapenem resistant Enterobacteriaceae have increased
      (bacteriaemia, abscesses, urinary tract infections...) with great difficulty in
      treatment and important associated comorbidity. We present the first case of
      infection of a lumbar instrumentation by Klebsiella pneumoniae producing
      carbapenemase D, OXA-48 type, and successfully treated.

PMID- 29636228
TI  - Clinical factors associated with lithium treatment response in bipolar disorder
      patients from India.
AB  - BACKGROUND: Bipolar Disorder (BD) is a chronic and disabling psychiatric illness
      with waxing and waning course. Lithium is the mainstay of treatment for Bipolar
      disorder (BD). There is limited literature on the clinical markers of Lithium
      treatment response from south Asia. METHODS: Two hundred and ten individuals with
      BD I and a history of at least 6 months of treatment with Lithium were recruited
      from the outpatient services of the National Institute of Mental Health and
      Neurosciences (NIMHANS) after obtaining informed consent. A diagnosis of BD I was
      made according to the DSM-IV criteria. The characterization of response to
      lithium prophylaxis was done using NIMH Retrospective Life Chart and
      "Retrospective Criteria of Long Term Treatment Response in Research Subjects with
      Bipolar Disorder" scale. RESULTS: There were 132 (62.86%) good responders and 78
      (37.14%) non-responders. Good responders were noted to have less number of
      hospitalizations and more onset episode of depression than non-responders. Using
      continuous phenotype, Lithium response was inversely correlated with total number
      of episodes, number of episodes of mania/ depression, number of hospitalisations
      and presence of suicide attempt. Multivariate analysis only revealed number of
      episodes and hospitalization to be associated with Lithium response. CONCLUSION:
      Our Lithium response rates were higher than what have been reported in the few
      previous studies. Illness severity was the only factor associated with Lithium
      response. There is a need to examine this question in larger prospective samples
      and to focus on biological/ molecular markers of treatment response.

PMID- 29636229
TI  - [Influence of a programme of therapeutic exercise on different clinical
      indicators related to dyslipidaemia in adult subjects aged between 26 to 73 years
      with a cardiovascular risk factor].
AB  - INTRODUCTION: A sedentary lifestyle is indicated in the international literature
      as one of the main causes for the onset of some cardiovascular risk factors.
      OBJECTIVE: To assess the effect of a therapeutic physical exercise programme on
      different clinical indicators related to dyslipidaemia (total cholesterol, HDL
      and LDL) in sedentary subjects with a cardiovascular risk factor. METHOD:
      Intervention study with before-and-after evaluation of a sample of 340 patients
      (132 males and 208 females) referred from the 2 primary care centres of the
      municipality of Molina de Segura (Murcia), and who participated in a 30-week
      programme of physical exercise combining muscle-conditioning work circuits with
      other cardio-respiratory resistance workouts. Regarding the clinical indicators,
      the health professionals collected in the medical history the health indicators
      corresponding to the biological evolution of the process for which the subjects
      studied had started the physical exercise programme. RESULTS: The statistical
      analyses showed a significant improvement (p<.005) in the LDL indicator and a non
      significant improvement in total and HDL cholesterol indicators after a 3-month
      exercise programme of 3 weekly sessions. CONCLUSIONS: The prescription of
      physical exercise in dyslipidaemic subjects from primary care centre should be
      evaluated as a resource for improving the clinical indicators specific to their
      pathology.

PMID- 29636230
TI  - Anti-apoptotic effect of Suxiao Jiuxin Pills against hypoxia-induced injury
      through PI3K/Akt/GSK3beta pathway in HL-1 cardiomyocytes.
AB  - BACKGROUND: Suxiao Jiuxin Pill (SX), Chinese traditional medicine primarily
      consisting of tetramethylpyrazine and borneol, has been shown to protect against
      ischemic heart diseases. Nevertheless, the involved mechanism still remains
      unclear. The following study aimed to investigate the potential protective effect
      and molecular mechanisms of SX on apoptosis in HL-1 cardiomyocytes. METHODS:
      Simulated hypoxia was established by culturing HL-1 cardiomyocytes in DMEM with
      no glucose or serum in a hypoxic chamber with 95% N2 and 5% CO2 for 24 h. HL-1
      cardiomyocytes were divided into 5 groups: control, hypoxic injury, hypoxic
      injury + insulin (PI3K agonist, 10 MUM), hypoxic injury + SX (100 MUg/mL), and
      hypoxic injury + SX + LY294002 (PI3K inhibitor, 10 MUM) (n = 3 wells/group). The
      anti-apoptotic effect of SX was evaluated by Annexin V/PI analysis. Mitochondrial
      membrane potential (DeltaPsim) was detected by JC-1 assay. The protein expression
      of PI3K, phosphorylated PI3K (p-PI3K), Akt, phosphorylated Akt (p-Akt), GSK3beta
      and phosphorylated GSK3beta (p-GSK3beta) were detected by western blot. RESULTS:
      SX exhibited anti-apoptotic effect in HL-1 cardiomyocytes; nonetheless, the
      effect was blocked by PI3K inhibitor LY294002. Also, the anti-apoptotic effect of
      SX was mediated by increased mitochondrial membrane potential (DeltaPsim).
      Furthermore, p-PI3K, p-Akt, and p-GSK3beta expressions were significantly
      increased after SX treatment, while they were all reduced after administration of
      LY294002. CONCLUSION: SX protects HL-1 cardiomyocytes from apoptosis induced by
      hypoxia, partly through enhancing the phosphorylation of PI3K/Akt/GSK3beta
      signaling pathway.

PMID- 29636231
TI  - The clinical impact of the novel tumor marker DR-70 in unresectable gastric
      cancer patients.
AB  - BACKGROUND: Gastric cancer tumor markers, such as carcinoembryonic antigen (CEA)
      and cancer antigen 19-9 (CA 19-9), have been applied in clinical practice to
      screen or monitor treatment responses. However, their sensitivity and specificity
      are unsatisfactory. Therefore, we assessed the novel tumor marker DR-70 and
      evaluated its performance in screening and response monitoring. METHODS: The
      study included newly diagnosed patients with advanced gastric cancer from March
      2012 to October 2015. We measured the DR-70, CEA, and CA 19-9 levels at the time
      of enrollment. The patients subsequently underwent chemotherapy. We followed-up
      the patients every 3 months; DR-70 levels and abdominal computed tomography scans
      were re-evaluated and repeated, respectively, at each follow-up. The correlation
      between treatment response and DR-70 level after chemotherapy was analyzed. The
      overall survival and progression-free survival rates were also evaluated.
      RESULTS: A total of 51 patients with gastric cancer were enrolled. Most (82.4%)
      had metastatic disease. At enrollment, the sensitivity of DR-70 in our study
      group was 78.4%, compared with 52.9% and 43.1% for CEA and CA 19-9, respectively.
      When we used the three tumor markers together, the sensitivity increased to
      80.4%. We observed a correlation between treatment response and DR-70 level after
      chemotherapy. No difference in either overall survival or progression-free
      survival was observed between the DR-70 positive and negative groups. However, a
      trend toward poorer overall survival was observed for the high DR-70 group,
      although this was not statistically significant. CONCLUSION: DR-70 is a powerful
      tool not only for screening unresectable gastric cancer but also for treatment
      response evaluation.

PMID- 29636232
TI  - Ethmoidal and extranodal Burkitt lymphoma in a child with bilateral kidney
      Burkitt lymphoma lesions incidentally detected by 18F-FDG PET/CT.

PMID- 29636233
TI  - Superior vena cava obstruction by metastatic mediastinal testicular seminoma.
      Imaging of collateral pathways during gastrointestinal bleeding scintigraphy with
      99mTc labeled red blood cells.

PMID- 29636234
TI  - The role of 68Ga-DOTATOC PET/CT in the detection of relapsed malignant solitary
      fibrous tumor of the pleura.

PMID- 29636235
TI  - Usefulness of 99mTc labelled heat-denatured red blood cell scintigraphy in the
      diagnosis of intramuscular splenosis.

PMID- 29636237
TI  - Health related quality of life in children with spina bifida in Uganda.
AB  - BACKGROUND: Studies on health related quality of life (HRQOL) of children with
      disabilities in low income countries are limited. OBJECTIVE: To inform
      interventions for children with spina bifida in low income countries, HRQOL of
      children with spina bifida and siblings, predictors, relationships between HRQOL
      and parental stress in Uganda were examined. METHODS: Demographic, impairment,
      daily, social functioning data, and HRQOL using the KIDSCREEN-10 were collected
      from 39 children, 33 siblings, and 39 parents from a cohort of families of
      children with spina bifida. T-tests, correlations, analysis of variance and
      regression analysis were used to compare means between children with spina bifida
      and their siblings, understand relationships between variables, and identify
      predictors of HRQOL. RESULTS: Children with spina bifida (N = 39) had lower HRQOL
      compared to their siblings (N = 33) (t = -3.868, p < .001 parental; t = -3.248, p
      = .002 child ratings). Parents (N = 39) indicated higher parental stress for
      their child with spina bifida (t = 2.143, p = 0.036). HRQOL child outcomes were
      predicted by the presence of hydrocephalus (beta = -.295, p = 0.013) for children
      with spina bifida, and daily functioning levels (beta = .336, p = 0.038), and
      parental support (beta = .357, p = 0.041) for siblings specifically. Parent rated
      HRQOL outcomes were predicted by parental distress (beta = -.337, p = 0.008),
      incontinence (beta = .423, p = 0.002), and daily functioning levels (beta = .325,
      p = 0.016) for children with spina bifida. CONCLUSIONS: To improve HRQOL
      investment in neurosurgical care, community based rehabilitation, incontinence
      management, and parental support are required. A combination of child friendly
      semi-structured and creative research methods are recommended to study HRQOL.

PMID- 29636236
TI  - Molecular detection of spotted fever group rickettsiae in ticks from Cameroon.
AB  - In western and eastern Africa, rickettsioses are one cause of fever in humans.
      Little is known regarding the presence of Rickettsia sp. in northern Cameroon.
      The present work was conducted in order to identify potential tick-borne spotted
      fever group Rickettsia in the Adamawa region of northern Cameroon, which may
      contribute filling some of the knowledge gaps of these pathogens. Ticks were
      collected from cattle in the municipal slaughterhouse of Ngaoundere in the
      Adamawa region of northern Cameroon. After morphological identification of tick
      species, extracted DNA was analyzed by PCR targeting the rickettsial ompB gene
      and the intergenic spacers dksA-xerC, mppA-purC and rpmE-tRNAfMet. Of the 316
      adult ticks collected, 149 (47.1%) were Amblyomma variegatum, 92 (29%)
      Rhipicephalus spp. and 75 (23.7%) Hyalomma spp. Through the use of conventional
      PCR assays for the rickettsial ompB gene, rickettsial DNA was detected in 104
      (32.9%) samples (85 Amblyomma sp., 14 Hyalomma spp. and 5 Rhipicephalus spp.).
      The ompB gene and the three intergenic were sequenced for 10 ticks in order to
      determine the rickettsial species. Rickettsia africae was detected in Amblyomma
      variegatum, Rickettsia aeschlimannii in Hyalomma rufipes and Hyalomma truncatum,
      Rickettsia sibirica in H. truncatum, Rickettsia massiliae in Rhipicephalus
      lunulatus and Candidatus Rickettsia barbariae in R. lunulatus. To the best of the
      author's knowledge, this report represents the first molecular evidence of
      rickettsial infection in ticks in the Adamawa region of northern Cameroon, which
      suggests a possible exposure of the human population in this region.

PMID- 29636238
TI  - In-vitro and in-vivo design and validation of an injectable polysaccharide
      hydroxyapatite composite material for sinus floor augmentation.
AB  - OBJECTIVE: Polysaccharide-based composite matrices consisting of natural
      polysaccharides, pullulan and dextran supplemented with hydroxyapatite (Matrix
      HA) have recently been developed. The principal objective of this study was to
      evaluate the capacities of this composite material to promote new bone formation
      in a sinus lift model in the sheep. Secondary objectives were to evaluate in
      vitro properties of the material regarding cell adhesion and proliferation.
      METHODS: In this report, once such composite matrix was prepared as injectable
      beads after dispersion in a physiological buffer, and evaluated using a large
      animal model (sheep) for a sinus lift procedure. RESULTS: In vitro studies
      revealed that these microbeads (250-550MUm in diameter) allow vascular cell
      adhesion and proliferation of Endothelial Cells (EC) after 1 and 7 days of
      culture. In vivo studies were performed in 12 adult sheep, and newly formed
      tissue was analyzed by Cone Beam Computed Tomography (CBCT scanning electron
      microscopy (SEM) and by histology 3 and 6 months post-implantation. CBCT analyses
      at the implantation time revealed the radiolucent properties of these matrices.
      Quantitative analysis showed an increase of a dense mineralized tissue in the
      Matrix-HA group up to 3 months of implantation. The mineralized volume over total
      volume after 6 months reached comparable values to those obtained for Bio-Oss(r)
      used as positive control. Histological examination confirmed that the Matrix-HA
      did not induce any long term inflammatory events, and promoted direct contact
      between the osteoid tissue and lamellar bone structures and beads. After 6
      months, we observed a dense network of osteocytes surrounding both biomaterials
      as well as a newly vascularized formed tissue in close contact to the
      biomaterials. SIGNIFICANCE: In conclusion, the absence of animal components in
      Matrix-HA, the osteoconductive property of Matrix-HA in sheep, resulting in a
      dense bone and vascularized tissue, and the initial radiolucent property to
      follow graft integration offer great promises of this composite material for
      clinical use.

PMID- 29636239
TI  - Clinical evaluation of the bulk fill composite QuiXfil in molar class I and II
      cavities: 10-year results of a RCT.
AB  - OBJECTIVE: The objective of this RCT was to compare the 10-year clinical
      performance of QuiXfil with that of Tetric Ceram in posterior single- or multi
      surface cavities. METHODS: 46 QuiXfil (Xeno III) and 50 Tetric Ceram (Syntac
      classic) composite restorations were placed in 14 stress bearing class I and 82
      class II cavities in first or second molars. Clinical evaluation was performed at
      baseline and after up to 10 years by using modified US Public Health Service
      criteria. At the last recall period, 26 QuiXfil and 30 Tetric Ceram restorations
      in 11 stress bearing class I and 45 class II cavities, were assessed. RESULTS:
      Ten failed restorations were observed during the follow-up period, four Tetric
      Ceram restorations failed due to secondary caries (2), tooth fracture (1) and
      bulk fracture combined with secondary caries (1) whereas six QuiXfil restorations
      failed due to secondary caries (1), tooth fracture (2), secondary caries combined
      with restoration fracture (1), restoration fracture (1) and postoperative
      sensitivity (1). Fisher's exact test yielded no significant difference between
      both materials (p=0.487). SIGNIFICANCE: Both materials, bulk fill QuiXfil
      restorations and Tetric Ceram restorations, showed highly clinical effectiveness
      during the 10-year follow-up.

PMID- 29636240
TI  - When and how should we perform a biopsy for HCC in patients with liver cirrhosis
      in 2018? A review.
AB  - The role of liver biopsy in the diagnosis of hepatocellular carcinoma (HCC) has
      changed over time. The diagnostic algorithm for this tumor is nowadays mainly
      based on radiological imaging, relegating histology to controversial cases, in
      which imaging techniques cannot establish a clear-cut diagnosis. This most
      commonly happens in small lesions, where biopsies frequently become mandatory, or
      in larger hypovascularized lesions. In this case however, the histological
      examination may not be reliable enough to grade the lesion, as different cell
      clones, deriving from sequential mutations, can originate heterogeneous cell
      populations. The risk of complications of liver biopsy, such as tumor seeding and
      intra-abdominal bleeding, needs to be reconsidered in light of new scientific
      evidence and of the technical improvements that have been introduced.
      Furthermore, increasing knowledge of the immunohistochemical and molecular
      characteristics of hepatocellular carcinoma opens a new scenario in which biopsy
      may play a decisive role in defining prognosis, and even treatment, by
      identifying the patient populations who could most benefit from target-driven
      hepatocellular carcinoma treatments, and therefore improving the success rate of
      experimental therapies. All the above reasons suggest that, overall, the role of
      liver biopsy in the management of HCC needs a reappraisal.

PMID- 29636241
TI  - A hairy polypoid lesion of the colon.

PMID- 29636242
TI  - Influence of additional reinforcement of fixed long-term temporary restorations
      on fracture load.
AB  - PURPOSE: In implant dentistry, temporary restorations (TR) might often be
      required for up to one year. The aim of this in vitro study was to evaluate the
      long-time performance of four-unit TRs in the posterior region based on different
      materials and reinforcement methods. METHODS: One hundred and forty four TRs were
      manufactured on 16 models simulating an oral situation of two missing posterior
      teeth. With a computer-aided-design/computer-aided-manufacturing (CAD/CAM)
      workflow, a TR was fabricated (CAD; Telio CAD), which served as a template for
      other subgroups. With a vacuum-formed template, unreinforced and reinforced TRs
      [glass fibres (g; EverStick); polyethylenefibres (p; Ribbond original) and TRs
      with increased connector area (c; 27.5-35mm2)] were manufactured. Two different
      composite materials were used (C1: Luxatemp, C2: Protemp). Altogether, 16
      subgroups with 8 specimens each were tested. After temporary luting (Temp Bond
      NE) and artificial-aging [1600 thermo-cycles (5-55 degrees C), 240,000 chewing
      cycles (50N)], all specimens were tested until fracture in a universal testing
      machine. RESULTS: After artificial aging, mean fracture loads (N) were:
      (C1)201.2+/-109.7, (C1c)1033.0+/-173.1, (C1p)90.0+/-40.0, (C1g)75.9+/-25.9,
      (C2)108.6+/-58.6, (C2c)1363.3+/-148.6, (C2p)104.7+/-54.7, (C2g)50.0+/-0.0 and
      (CAD)232.5+/-19.1. The one-factor ANOVA analysis showed significant differences
      for the factors temporary material (p<0.047), reinforcement (p<0.0001) and
      artificial-aging (p<0.0001). CONCLUSIONS: The study indicated that both CAD/CAM
      TRs and TRs with increased connector areas are suitable for long-term use of one
      year. No enhancement of fracture load was observed for fibre-reinforced TRs
      except for the fact that fractured TRs were not totally separated.

PMID- 29636244
TI  - Spontaneous hemoperitoneum during pregnancy. Is there any place for a wait and
      see approach in the absence of maternal hypovolemic shock or fetal distress?

PMID- 29636243
TI  - Surface morphology of silicone soft relining material after mechanical and
      chemical cleaning.
AB  - PURPOSE: The objective was to investigate the influence of chemical and
      mechanical cleaning on the surface morphology of a silicone soft relining
      material. METHODS: Three plate-shaped specimens were prepared for each group
      (Control, Hard and Soft) by laminating a 1.5-mm-thick silicone soft relining
      material. The Control group specimens were stored in water, and the Hard and Soft
      group specimens were cleaned with hard and soft bristle denture brushes,
      respectively. Abrasion testing with a toothbrush and immersion testing with an
      enzyme-containing peroxide denture cleanser were performed, simulating a period
      of approximately 4 months. The arithmetic mean roughness (Sa) and maximum height
      of the cross-section (Sz) were measured before and after abrasion and immersion
      testing. RESULTS: Sa was 4.9+/-0.9, 22.1+/-4.2 and 44.2+/-4.0MUm in the Control,
      Soft and Hard groups, respectively. Sz was 257.5+/-31.7, 392.0+/-23.8 and 452.2+/
      41.9MUm in the Control, Soft and Hard groups, respectively. After abrasion
      testing, Sa and Sz differed significantly between the Soft and Control groups and
      between the Hard and Control groups. Sa was 2.2+/-1.2MUm before and after
      immersion, and Sz was 142.1+/-81.4MUm before and after immersion. No significant
      difference was noted in either Sa or Sz in the Control specimens before or after
      immersion. CONCLUSIONS: Surfaces cleaned using a soft bristle brush were less
      likely to roughen than those cleaned with a hard bristle brush under the
      conditions of this study. Additionally, chemical cleaning using the
      enzyme+neutral peroxide denture cleanser did not roughen the surface of the
      silicone soft relining material.

PMID- 29636245
TI  - Vascular complication after embolization of uterine arteries for postpartum
      hemorrhage, a case of external iliac artery injury.

PMID- 29636246
TI  - Evaluation of a two-stage testing algorithm for the diagnosis of respiratory
      viral infections.
AB  - New on-demand multiplex molecular respiratory viral diagnostics offer superior
      performance although can be expensive and some platforms cannot process multiple
      specimens simultaneously. We performed a retrospective study reviewing results of
      patients tested for respiratory viruses following introduction of a two-stage
      testing algorithm incorporating an initial screen with Sofia(r) immunoassay then
      secondary Biofire Filmarray(r), and compared to a period when only Filmarray(r)
      was used. Of 2976 testing episodes, 1814 underwent initial Sofia(r) then follow
      up FilmArray(r). A diagnosis of influenza was made by Sofia(r) in 282 patients,
      and by FilmArray(r) in an additional 163 (median time to result 1.12hours versus
      3.46hours, P<0.001). Significantly more patients received their diagnosis within
      90minutes in winter despite testing more samples (11.1% versus 3.4%, P<0.001),
      and approximately $36,000 was saved. An algorithmic approach to respiratory viral
      diagnosis can combine the advantages of accuracy and speed and be cost saving.

PMID- 29636247
TI  - No changes on viral load and CD4+ T-cell counts following immunization with 7
      valent pneumococcal conjugate vaccine among HIV-infected adults in Malawi.
AB  - Vaccination has been associated with a transient increase in viremia in HIV
      infected individuals, although contradicting evidence persist in the literature.
      As part of a randomized placebo-controlled efficacy trial of the PCV7 in Malawi,
      we collected viral load and CD4+ T-cell counts from 237 adults who received two
      doses of vaccine or placebo, administered 4 weeks apart. Analyses were conducted
      separately for cART and non-cART users. Our analysis show no difference in viral
      loads between vaccine and placebo groups, regardless of cART use. Viremia
      decreased from 4.1 to 2.9 log10 copies/mL (p < 0.0001) among those using cART,
      consistent vaccine and placebo groups, but no changes were seen among the non
      cART cohort. CD4+ T-cell counts remained unchanged regardless of cART use, or
      allocation to vaccine or placebo. We concluded that there was no evidence of
      detrimental effects of PCV7 administration on viral load or CD4+ T-cell counts
      six months after vaccination with PCV7.

PMID- 29636248
TI  - The Impact of an Acute, Traumatic Wound Dehiscence on Clinical Outcomes Following
      Primary Knee Arthroplasty.
AB  - BACKGROUND: Early wound healing complications and persistent drainage are
      associated with an increased risk of infection following knee arthroplasty.
      However, the scenario in which a patient sustains an acute, traumatic wound
      dehiscence has not been investigated. The purpose of this study is to determine
      the outcomes of an acute traumatic wound dehiscence following arthroplasty
      treated with an urgent irrigation and debridement and primary wound closure.
      METHODS: Using a single institution's arthroplasty registry, patients sustaining
      an acute, traumatic wound dehiscence within 30 days of undergoing a primary knee
      arthroplasty were identified. Patients experiencing chronic wound drainage
      without injury or a history of prior infection were excluded. Patients were
      followed for the occurrence of complications and clinical outcomes using the Knee
      Society Score. RESULTS: From 2006 to 2016, 14 of 25,819 eligible patients (0.05%)
      were identified as having a traumatic wound dehiscence. The mean time from
      arthroplasty to wound dehiscence was 9.3 days. All but one patient was treated
      operatively within 24 hours of dehiscence. Postoperative antibiotics were
      administered for a mean of 21 days. At a mean of 6.5 years, 6 patients were
      considered failures (43%) including 2 deep infections, 3 revisions for
      instability, and 1 patient with a Knee Society Score <60 points. CONCLUSION:
      Despite emergent incision and drainage and wound closure, patients experiencing
      an acute traumatic wound dehiscence following knee arthroplasty subsequently
      exhibit high rates of reoperation for instability, periprosthetic infection, and
      clinical failure. Further work is required to better understand the optimal modes
      of treatment for this complication.

PMID- 29636249
TI  - Periprosthetic Joint Infection With Fungal Pathogens.
AB  - BACKGROUND: Although there is abundant information about bacterial periprosthetic
      joint infections (PJIs), there is a notable paucity of information about fungal
      PJIs. The goals of this study are to describe the patient demographics,
      diagnostic findings, and treatment results of fungal PJIs after total joint
      arthroplasty. METHODS: We identified 31 fungal PJIs (13 total hip arthroplasties
      and 18 total knee arthroplasties) in 31 patients treated between 1996 and 2014.
      This represented 0.9% of the 3525 PJIs treated at our institution during this
      time period. Candida species accounted for 81% of infections. The mean patient
      age at diagnosis of fungal PJI was 68 years. Mean follow-up after initiation of
      treatment was 4 years. RESULTS: In the total hip arthroplasty cohort,
      survivorship free from all-cause revision or implant removal was 44% at 2 years.
      Survivorship free from reinfection was 38% at 2 years. Mean Harris hip score was
      27 at final follow-up.In the total knee arthroplasty cohort, survivorship free
      from all-cause revision was 70% at 2 years. Survivorship free from reinfection
      was 76% at 2 years. Mean Knee Society scores were 36 at final follow-up.
      CONCLUSION: Fungal PJIs are rare (0.9% of diagnosed PJIs). Survivorship free of
      all-cause revision or implant removal was very low in the hip group (44% at 2
      years), but slightly better in the knee group (70% at 2 years). Moreover,
      clinical outcomes were poor with high perioperative complication rates. Improved
      treatment regimens are needed for this unsolved clinical problem.

PMID- 29636251
TI  - Re "Calcification of Thoracic and Abdominal Aneurysms is Associated with
      Mortality and Morbidity". Abdominal Aortic Aneurysm Calcification: Are
      Biochemical Markers a Missing Piece of the Puzzle?

PMID- 29636250
TI  - Elective Repair of Abdominal Aortic Aneurysm and the Risk of Colonic Ischaemia:
      Systematic Review and Meta-Analysis.
AB  - INTRODUCTION: Colon ischaemia (CI) is a significant complication of open (OR) and
      endovascular (EVAR) repair of abdominal aortic aneurysm (AAA). With a rapid
      increase in EVAR uptake, contemporary data demonstrating the differing rates and
      outcomes of CI between EVAR and OR, particularly in the elective setting, are
      lacking. The aim was to characterise the risk and consequences of CI in elective
      AAA repair comparing EVAR with OR. METHODS: A systematic review and meta-analysis
      of the literature was performed using the Cochrane collaboration protocol and
      reported according to the PRISMA guidelines. PubMed, MedLine, and EMBASE were
      searched for studies reporting CI rates after elective AAA repair. Ruptured AAAs
      were excluded from analysis. RESULTS: Thirteen studies reporting specific
      outcomes of CI after elective AAA repair, containing 162,750 evaluable patients
      (78,151 EVAR and 84,599 OR) were included. All studies found a higher risk of CI
      with OR than with EVAR. Three studies performed confounder adjustment with CI
      rates of 0.5-1% versus 2.1-3.6% (EVAR vs. OR) and combined odds ratio of 2.7 (2.0
      3.5) for the development of CI with OR versus EVAR. The majority of cases of CI
      occurred within 30 days and were associated with variable mortality (0-73%) and
      re-intervention rates (27-54%). GRADE assessment of evidence strength was very
      low for all outcomes. There was a high degree of heterogeneity between studies
      both methodologically and in terms of CI rates, re-intervention, mortality, and
      time to development of CI. CONCLUSIONS: EVAR is associated with a reduced
      incidence of CI compared with OR.

PMID- 29636252
TI  - Clinical Effect and Cost-Effectiveness of Screening for Asymptomatic Carotid
      Stenosis: A Markov Model.
AB  - OBJECTIVE/BACKGROUND: The cost-effectiveness of screening depends on the cost of
      screening, prevalence of asymptomatic carotid artery stenosis (ACAS), and the
      potential effect of medical intervention in reducing the risk of stroke. The aim
      of the study was to determine the threshold values for these parameters in order
      for screening for ACAS to be cost-effective. METHODS: The clinical effect and
      cost-effectiveness of ultrasound screening for ACAS with subsequent initiation of
      preventive therapy versus not screening was assessed in a Markov model with a
      lifetime perspective. Key parameters, including stroke risk, all cause mortality,
      and costs, were based on contemporary published data, population statistics, and
      data from an ongoing screening program in Uppsala county (population 300,000),
      Sweden. Prevalence of ACAS (2%) and the rate of best medical treatment (BMT; 40%)
      were based on data from a male Swedish population recently screened for ACAS. The
      required stroke risk reduction from BMT, incremental cost-efficiency ratio
      (ICER), absolute risk reduction for stroke (ARR), and number needed to screen
      (NNS) were calculated. RESULTS: Screening was cost-effective at an ICER of ?5744
      per incremental quality adjusted life year (QALY) gained. ARR was 135 per 100,000
      screened, NNS was 741, and QALYs gained were 6700 per 100,000 invited. At a
      willingness to pay (WTP) threshold of ?50,000 per QALY the minimum required
      stroke risk reduction from BMT was 22%. The assumed degree of stroke risk
      reduction was the most important determinant of cost-efficiency. CONCLUSION: A
      moderate (22%) reduction in the risk of stroke was required for an ACAS screening
      strategy to be cost-effective at a WTP of ?50,000/QALY. Targeting populations
      with a higher prevalence of ACAS could further improve cost-efficiency.

PMID- 29636253
TI  - Combined Impact of Chronic Kidney Disease and Contrast Induced Acute Kidney
      Injury on Long-term Outcomes in Patients with Acute Lower Limb Ischaemia.
AB  - INTRODUCTION: Acute lower limb ischaemia (ALI) is the sudden onset of decreased
      arterial perfusion with imminent threat to limb viability. Contrast induced acute
      kidney injury (CI-AKI) is one of the complications that increases mortality in
      patients who undergo contrast imaging in coronary procedures. The goal of this
      study is to evaluate the impact of chronic kidney disease (CKD) and CI-AKI on
      long-term clinical outcomes in patients with ALI undergoing lower limb
      revascularisation. METHODS: A total 1017 consecutive patients with acute lower
      limb ischaemia who were admitted between July 1, 2006, and January 1, 2017, were
      retrospectively reviewed. Patients who had end stage renal disease, those who had
      end stage heart and malignant disease and died within 7 days of limb
      revascularisation, and those who did not undergo angiography were excluded. Thus
      546 patients were included in the final analysis. Patients were classified as
      with or without CKD and were then subdivided according to the presence or absence
      of the development of CI-AKI, defined as an increase in serum creatinine of >=0.5
      mg/dL or by >=25% from the baseline value within the first 72 h after contrast
      exposure. The primary end point was all cause mortality and secondary major
      adverse limb event (MALE). RESULTS: Both CKD and CI-AKI were associated with the
      highest rate of all cause mortality (chi square = 55.77, d.f. = 1, p < .01, log
      rank test) and MALE (chi square = 79.07, d.f. = 1, p < .01, log rank test). The
      presence of CKD and CI-AKI were significant risk factors associated with long
      term all cause mortality (HR = 2.61, p < .01) and MALE (HR = 2.87, p < .01).
      CONCLUSION: In patients with ALI undergoing lower limb revascularisation, both
      CKD and CI-AKI were significantly associated with poor long-term outcomes
      compared with either CKD or CI-AKI alone. Further studies are required to assess
      this association and to confirm the combined effect of CKD and CI-AKI on long
      term clinical outcomes.

PMID- 29636255
TI  - Sacral Neuromodulation and OnabotulinumtoxinA for Refractory Urge Urinary
      Incontinence Offer Similar Success During 2-Year Follow-up.

PMID- 29636256
TI  - Re: Value of an Immediate Intravesical Instillation of Mitomycin C in Patients
      with Non-muscle-invasive Bladder Cancer: A Prospective Multicentre Randomised
      Study in 2243 patients.

PMID- 29636254
TI  - Expression of Saccharomyces cerevisiae cDNAs to enhance the growth of non-ethanol
      producing S. cerevisiae strains lacking pyruvate decarboxylases.
AB  - Metabolic engineering of Saccharomyces cerevisiae often requires a restriction on
      the ethanol biosynthesis pathway. The non-ethanol-producing strains, however, are
      slow growers. In this study, a cDNA library constructed from S. cerevisiae was
      used to improve the slow growth of non-ethanol-producing S. cerevisiae strains
      lacking all pyruvate decarboxylase enzymes (Pdc-, YSM021). Among the obtained 120
      constructs expressing cDNAs, 34 transformants showed a stable phenotype with
      quicker growth. Sequence analysis showed that the open reading frames of PDC1,
      DUG1 (Cys-Gly metallo-di-peptidase in the glutathione degradation pathway), and
      TEF1 (translational elongation factor EF-1 alpha) genes were inserted into the
      plasmids of 32, 1, and 1 engineered strains, respectively. DUG1 function was
      confirmed by the construction of YSM021 pGK416-DUG1 strain because the specific
      growth rate of YSM021 pGK416-DUG1 (0.032 +/- 0.0005 h-1) was significantly higher
      than that of the control strains (0.029 +/- 0.0008 h-1). This suggested that
      cysteine supplied from glutathione was probably used for cell growth and for
      construction of Fe-S clusters. The results showed that the overexpression of
      cDNAs is a promising approach to engineer S. cerevisiae metabolism.

PMID- 29636257
TI  - The collapse of the Venezuelan health system.

PMID- 29636258
TI  - Health-care system transition in China.

PMID- 29636259
TI  - Privatising versus prioritising veterans' health.

PMID- 29636260
TI  - Clinical Pictures in The Lancet: a good eye for detail.

PMID- 29636261
TI  - Measuring Humanity: hip-hop as evidence for health inequalities.

PMID- 29636262
TI  - Offline: UHC-one promise and two misunderstandings.

PMID- 29636263
TI  - Violence rife in Mexico, affecting medical community.

PMID- 29636264
TI  - Progress in influenza surveillance in Africa.

PMID- 29636265
TI  - Getting back in touch.

PMID- 29636266
TI  - WHOse health agenda? 70 years of struggle over WHO's mandate.

PMID- 29636267
TI  - Polio transition: overlooked challenges.

PMID- 29636268
TI  - On the misuses of medical history.

PMID- 29636269
TI  - C1 esterase inhibitor concentrates and attenuated androgens.

PMID- 29636270
TI  - C1 esterase inhibitor concentrates and attenuated androgens - Authors' reply.

PMID- 29636271
TI  - Department of Error.

PMID- 29636272
TI  - Efficacy of cabazitaxel rechallenge in heavily treated patients with metastatic
      castration-resistant prostate cancer.
AB  - BACKGROUND: Treatment option in patients with metastatic castration-resistant
      prostate cancer (mCRPC) previously treated with docetaxel (DOC), cabazitaxel
      (CABA) and new hormone therapy (NHT) is limited. Rechallenge with DOC is limited
      because of cumulative toxicities. This study investigated the activity and safety
      of CABA rechallenge in mCRPC. PATIENTS AND METHODS: Clinical data were collected
      retrospectively in 17 centres in Europe. Eligible patients had undergone
      rechallenge with cabazitaxel after three previous lines of treatment (DOC, NHT
      and CABA, in any order). Overall survival (OS) and progression-free survival
      (PFS) were estimated by the Kaplan-Meier method. Data on toxicities were
      collected. RESULTS: A total of 69 of 562 patients (Eastern Cooperative Oncology
      Group performance status 0-1 69%) were rechallenged with CABA (25 mg/m2 q3w, 58%;
      20 mg/m2 q3w, 27.5%; other, 14.5%) for 1-10 (median 6) cycles; 76.8% received
      prophylactic granulocyte colony-stimulating factor. Median radiological or
      clinical PFS with CABA rechallenge was 7.8 months and 11.9 months with initial
      CABA therapy. OS was 13.7 months (95% confidence interval [CI]: 9.3-15.7) from
      the first CABA rechallenge cycle, 59.9 months (47.8-67.1) from the first life
      extending therapy in mCRPC and 78.3 months (66.4-90.7) from mCRPC diagnosis. Best
      clinical benefit was improved (34.3%) or stable (47.8%). Lack of response to
      rechallenge occurred in 17.9% of patients (3.1% with initial CABA). The level of
      prostate-specific antigen decreased by >= 50% in 24% of patients at rechallenge
      (71% with initial CABA). There was no grade >=III peripheral neuropathy or nail
      disorders. CONCLUSIONS: CABA rechallenge may be a treatment option without
      cumulative toxicity in heavily pretreated patients with mCRPC who are still fit
      and had a progression >3 months after the last CABA injections.

PMID- 29636273
TI  - High body mass index, healthy metabolic profile and low visceral adipose tissue:
      The paradox is to call it obesity again.

PMID- 29636274
TI  - The NET-effect of combining rituximab with belimumab in severe systemic lupus
      erythematosus.
AB  - OBJECTIVE: In systemic lupus erythematosus (SLE) patients, excessive formation of
      neutrophil extracellular traps (NETs) is observed and their degradation is
      impaired. In vitro, immune complexes (ICx) trigger NET formation while NET
      derived DNA is a postulated autoantigen for anti-nuclear autoantibodies (ANAs),
      found in SLE. Based on these self-perpetuating mechanisms in SLE, this study
      investigates whether interfering with ICx formation using a combination of
      rituximab (RTX) and belimumab (BLM) could decrease NET formation and ameliorate
      disease. METHODS: A phase 2A, open-label, single arm proof-of-concept study was
      performed wherein 16 SLE patients with severe, refractory disease were treated
      with a combination of CD20-mediated B-cell depletion with rituximab and sustained
      inhibition of B-cell activating factor BlyS with belimumab. Besides safety, the
      study's endpoints were chosen to address the concept of autoantibodies in
      relation to excessive NET formation. RESULTS: We demonstrated a surge of BlyS
      levels upon RTX-mediated B-cell depletion which was abrogated by subsequent BLM
      treatment. As such, therapeutic intervention with RTX + BLM led to specific
      reductions in ANAs and regression of excessive NET formation. RTX + BLM appeared
      to be safe and achieved clinically significant responses: low lupus disease
      activity state was achieved in 10 patients, renal responses in 11 patients and
      concomitant immunosuppressive medication was tapered in 14 out of the 16
      patients. CONCLUSIONS: This study provides novel insights into clinical
      beneficence of reducing excessive NET formation in SLE by therapeutic targeting
      ANA production with RTX + BLM. Altogether putting forward a new treatment concept
      that specifically ameliorates underlying SLE pathophysiology. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT02284984.

PMID- 29636275
TI  - [Radiation protection measures: Implications on the design of neurosurgery
      operating rooms].
AB  - OBJECTIVE: To describe pros and cons of some radiation protection measures and
      the implications on the design of a neurosurgery operating room. MATERIAL AND
      METHODS: Concurring with the acquisition and use of an O-arm device, a structural
      remodeling of our neurosurgery operating room was carried out. The theater was
      enlarged, the shielding was reinforced and a foldable leaded screen was installed
      inside the operating room. Radiation doses were measured in front of and behind
      the screen. RESULTS: The screen provides whole-body radiation protection for all
      the personnel inside the theater (effective dose <5MUSv at 2,5 m from the gantry
      per O-arm exploration; 0,0MUSv received behind the screen per O-arm exploration;
      and undetectable cumulative annual radiation dose behind the screen), obviates
      the need for leaded aprons and personal dosimeters, and minimizes the circulation
      of personnel. Enlarging the size of the operating room allows storing the
      equipment inside and minimizes the risk of collision and contamination.
      Rectangular rooms provide greater distance from the source of radiation.
      CONCLUSION: Floor, ceiling and walls shielding, a rectangular-shaped and large
      enough theater, the presence of a foldable leaded screen, and the security
      systems precluding an unexpected irruption into the operating room during
      irradiation are relevant issues to consider when designing a neurosurgery
      operating theater.

PMID- 29636276
TI  - Modified Le Fort III osteotomy: A simple solution to severe midfacial hypoplasia.
AB  - PURPOSE: There are multiple conditions that may affect the development of the
      middle third of the face and with varying degrees of severity. The surgical
      treatment alternatives for major midfacial sagittal deficiencies consist in Le
      Fort I, II, or III with conventional osteotomies or with distraction osteogenesis
      (DO). Both techniques have advantages and disadvantages that should be evaluated
      specifically in each case. The aim of this report is to present a group of
      patients with severe hypoplasia of the middle third of the face, with different
      origins, and their treatment with a Modified Le Fort III osteotomy and
      distraction osteogenesis, using a minimally invasive surgical approach. MATERIALS
      AND METHODS: The surgical technique was performed in a group of patients with
      severe hypoplasia of the middle third of the face, through a transconjunctival
      approach with lateral canthotomy and a trans-oral approach. The osteotomy
      consisted of a Le Fort III without the nasofrontal component. A rigid external
      distractor (RED) type II or internal distractor was installed. The amount of
      distraction, surgical time, blood loss, and complications were evaluated.
      RESULTS: A total of 7 patients underwent operation, 5 men and 2 women with an
      average age of 20.8 (range 11-41) years; 3 patients with Crouzon syndrome, 2 with
      Pfeiffer syndrome, 1 patient with cleft lip and palate sequel, and 1 with a
      severe non-syndromic class III. The average follow-up was 3.14 years. All
      patients achieved stable occlusion without postoperative changes, positive
      overbite and overjet, without relapse in the skeletal position. The average
      advancement was 14.7 (+/-4.07) mm, in 1.1 incisors, and 15.2 (+/-3.19) in point
      A. The average time of surgery was 2.78 (+/-0.64) hours, with an average blood
      loss of 240 (+/-48.6) ml. Four patients required a rhinoplasty in a secondary
      surgery. CONCLUSION: This technique shows a surgical approach with low morbidity,
      short surgery time, and low blood loss. It allows optimal resolution of severe
      hypoplasia of the middle third of the face with long-term stability. It avoids
      the use of grafts and osteosynthesis material. By not including the nasal pyramid
      in the osteotomy design, the size, position, and nasofrontal angle in patients
      with adequate facial balance is maintained. If nasal correction is necessary, a
      second surgery may be done. In cases of asymmetrical hypoplasia of the middle
      third, this osteotomy shows great versatility and can be done unilaterally and/or
      simultaneously combined with other distractions.

PMID- 29636277
TI  - Biocatalytic strategies for the production of high fructose syrup from inulin.
AB  - The consumption of natural and low calorie sugars has increased enormously from
      the past few decades. To fulfil the demands, the production of healthy sweeteners
      as an alternative to sucrose has recently received considerable interest.
      Fructose is the most health beneficial and safest sugar amongst them. It is
      generally recognised as safe (GRAS) and has become an important food ingredient
      due its sweetening and various health promising functional properties.
      Commercially, high fructose syrup is prepared from starch by multienzymatic
      process. Single-step enzymatic hydrolysis of inulin using inulinase has emerged
      as an alternate to the conventional approach to reduce complexity, time and cost.
      The present review, outlines the enzymatic strategies used for the preparation of
      high fructose syrup from inulin/inulin-rich plant materials in batch and
      continuous systems, and its conclusions.

PMID- 29636278
TI  - Characterization of hemangioma by nuclear medicine techniques.

PMID- 29636279
TI  - Perspectiva actual hospitalization in inflammatory bowel disease: Current
      perspective.

PMID- 29636280
TI  - Surgical management of a patent ductus arteriosus: Is this still an option?
AB  - The evolution of neonatal intensive care over the past decade has seen the role
      of surgical patent ductus arteriosus (PDA) ligation in preterm infants both
      decrease in scope and become laden with uncertainty. Associations of ligation
      with adverse neonatal and neurodevelopmental outcomes have rendered the ligation
      decision more challenging for clinicians and have been associated with a decline
      in surgical treatment, but these findings may be due to bias from confounding by
      indication in observational studies rather than a causal detrimental effect of
      ligation. Accordingly, ligation may still be indicated for infants with large
      ductal shunts and moderate-severe respiratory insufficiency in whom the prospect
      of timely spontaneous closure appears low. Ultimately a randomized trial of
      surgical ligation versus conservative management is necessary to assess the
      efficacy of this invasive intervention in a population of extremely preterm
      infants with large ductal shunts. Simultaneously, the transcatheter approach to
      ductal closure in the very immature infant represents an exciting therapeutic
      alternative but which is still in its infancy. Insights into the pathophysiology
      of postoperative cardiorespiratory deterioration, including the importance of
      left ventricular afterload, may help clinicians avoid instability and mitigate a
      potentially injurious aspect of surgical treatment. This review examines the
      evidence regarding the benefits and risks of PDA surgery in preterm neonates and
      provides a pathophysiology-based management paradigm to guide perioperative care
      in high-risk infants.

PMID- 29636281
TI  - IgA nephropathy: What patients are at risk of progression to end-stage renal
      disease and how should they be treated?

PMID- 29636282
TI  - Pazopanib in the Treatment of Bilateral Multifocal Renal Oncocytomas: A Case
      Report.

PMID- 29636283
TI  - Current, future and potential use of mobile and wearable technologies and social
      media data in the ABCD study to increase understanding of contributors to child
      health.
AB  - Mobile and wearable technologies and novel methods of data collection are
      innovating health-related research. These technologies and methods allow for
      multi-system level capture of data across environmental, physiological,
      behavioral, and psychological domains. In the Adolescent Brain Cognitive
      Development (ABCD) Study, there is great potential for harnessing the
      acceptability, accessibility, and functionality of mobile and social technologies
      for in-vivo data capture to precisely measure factors, and interactions between
      factors, that contribute to childhood and adolescent neurodevelopment and
      psychosocial and health outcomes. Here we discuss advances in mobile and wearable
      technologies and methods of analysis of geospatial, ecologic, social network and
      behavioral data. Incorporating these technologies into the ABCD study will allow
      for interdisciplinary research on the effects of place, social interactions,
      environment, and substance use on health and developmental outcomes in children
      and adolescents.

PMID- 29636284
TI  - Assessing bottlenecks in Emergency Department flow of patients with abdominal
      pain.
AB  - INTRODUCTION: Abdominal pain has a wide range of possible causes, which may lead
      to difficulties in diagnosing and lengthy Emergency Department (ED) stays. In
      this study, bottlenecks in ED processes of patients with abdominal pain were
      identified. METHODS: Time-points of patients who presented to a Dutch ED with
      abdominal pain were observed and documented. The institutional review board
      approved the study. RESULTS: In total, 3015 min of patient time were observed in
      54 patients. Median length of stay (LOS) was 218 min for admitted patients, and
      168 min for discharged patients. For 65 patients (27.4%), LOS exceeded 4 h.
      Delays were found during the diagnostic process, when multiple physicians were
      needed in order to make a decision, and during departure. CONCLUSIONS: Our study
      concerning individual patients' time-points provides important insight into
      delays in the patient journey of patients with abdominal pain. Flow improvement
      can be achieved by focusing on these bottlenecks, for example by minimizing
      diagnostic delays and by simultaneous specialists' consultations for patients who
      need more than one physician. The optimization of ED flow for patients with
      abdominal pain depends on coordinated efforts between ED staff, medical
      specialists, radiology and laboratory staff, staff from inpatient units, and
      hospital supporting services.

PMID- 29636285
TI  - Identification of a new variant of Chlamydia trachomatis in Mexico.
AB  - INTRODUCTION: Chlamydia trachomatis is one of the main etiological agents of
      sexually transmitted infections worldwide. In 2006, a Swedish variant of C.
      trachomatis (Swedish-nvCT), which has a deletion of 377bp in the plasmid, was
      reported. In Latin America, Swedish-nvCT infections have not been reported. We
      investigated the presence of Swedish-nvCT in women with infertility in Mexico.
      METHODS: Swedish-nvCT was searched in 69C. trachomatis positive samples from 2339
      endocervical specimens. We designed PCR primers to identify the deletion in the
      plasmid in the ORF1, and the presence of a repeated 44bp in the ORF3. The sample
      with the deletion was genotyped with the genes of the major outer membrane
      protein A (ompA) and the polymorphic membrane protein (pmpH). RESULTS: The
      deletion was detected in one of the 69 samples positive C. trachomatis of 2339
      endocervical exudates. The nucleotide sequence analysis of the ompA shows a high
      degree of similarity with the Swedish nvCT (98%), however the variant found
      belongs to serovar D. The nucleotide sequence of the pmpH gene associates to the
      variant found in the genitourinary pathotype of the Swedish-nvCT but in different
      clusters. CONCLUSIONS: Our results revealed the presence of a new variant of C.
      trachomatis in Mexican patients. This variant found in Mexico belongs to serovar
      D based on the in silico analysis of the ompA and pmpH genes and differs to the
      Swedish-nvCT (serovars E). For these variants of C. trachomatis that have been
      found it is necessary to carry out a more detailed analysis, although the role of
      this mutation has not been demonstrated in the pathogenesis.

PMID- 29636286
TI  - Corrigendum to "Morphometric analysis of the cerebral expression of ATP-binding
      cassette transporter protein ABCB1 in chronic schizophrenia: Circumscribed
      deficits in the habenula" [Schizophr. Res. 2016 Nov;177(1-3):52-58].

PMID- 29636287
TI  - Letter to the Editor: Left-handedness and rTMS for auditory verbal
      hallucinations: Should left-handers be treated the same as right-handers?

PMID- 29636288
TI  - Biomarkers of Alzheimer's disease in mild cognitive impairment: Experience in a
      memory clinic from Latin America.
AB  - OBJECTIVE: This study aimed to investigate the role and prognosis of Alzheimer
      disease biomarkers in patients with mild cognitive impairment (MCI) at a memory
      clinic in Latin America. METHODS: We studied 89 patients with MCI, 43 with
      Alzheimer-type dementia, and 18 healthy controls (matched for age, sex, and
      educational level) at our memory clinic (Instituto FLENI) in Buenos Aires,
      Argentina. Patients and controls underwent an extensive demographic,
      neurological, and neuropsychological assessment. All subjects underwent a brain
      MRI scan; FDG-PET scan; amyloid PET scan; apolipoprotein E genotyping; and
      cerebrospinal fluid concentrations of Abeta1-42, tau, and phosphorylated tau.
      Patients were categorised as positive or negative for the presence of amyloid
      pathology and neurodegeneration. RESULTS: Amyloid pathology was observed in
      cerebrospinal fluid results in 18% of controls, 64% of patients with MCI, and 92%
      of patients with Alzheimer-type dementia. Suspected non-Alzheimer disease
      pathophysiology was found in 11% of controls, 6% of patients with MCI, and 8% of
      patients with Alzheimer-type dementia. At 30 months of follow-up, 45% of amyloid
      positive patients with MCI and 20% of amyloid-negative patients with MCI showed
      progression to dementia. CONCLUSIONS: This study demonstrates biomarker-based MCI
      prognosis and supports its role in clinical decision-making in daily practice.

PMID- 29636289
TI  - Folic acid protects against experimental prenatal nicotine-induced cardiac injury
      by decreasing inflammatory changes, serum TNF and COX-2 expression.
AB  - Nicotine administration has been shown to increase the risk for cardiovascular
      diseases and death. The present study was designed to investigate the impact of
      nicotine administration on serum level tumor necrosis factor and cycloxygenase -2
      (COX-2) expression mediated cardiac injury in rat off springs, and the possible
      protective effect of folic acid. Eighteen pregnant female rats were randomly
      divided into three groups, six animals each. Control group received the vehicle,
      nicotine group received a dose of nicotine 0.1 mg/kg body weight, daily with
      subcutaneous injection from day 3 of gestation until weaning on postnatal day 21.
      Nicotine treated group received daily oral supplementation with folic acid 200
      mg/kg body weight by intragastric tube prior to injection of nicotine. In serum
      of the pups, levels of tumor necrosis factor (TNF), nitric oxide (NO), total
      antioxidant capacity (TAC) and malondialdehyde (MDA) were measured.
      Histopathological studies of cardiac tissues using hematoxylin-eosin (H&E) were
      carried out. The expression of COX-2 was evaluated using immunohistochemistry.
      Serum TNF and MDA were significantly increased, while serum NO and TAC were
      significantly decreased in nicotine group. Moreover, nicotine-exposed rats showed
      complete lysis of cardiac myocytes, marked cytoplasmic vacuolation of myocytes,
      muscle fibers show loss of striation and increased COX-2 expression. Concomitant
      folic acid administration resulted in a significant alleviation of biochemical
      and structural alteration-induced by nicotine. In conclusion, folic acid has a
      protective role against nicotine induced cardiac injury by reduction of COX-2
      expression, decreasing TNF production and lipid peroxidation mediated cell
      injury.

PMID- 29636290
TI  - [Family violence prevalence in patients from the Gerontology Module of a Family
      Medicine clinic].

PMID- 29636291
TI  - [Identification of single nucleotide polymorphisms related to frailty].
AB  - INTRODUCTION: The search for biomarkers that can lead to the early diagnosis and
      thus, early treatment of frailty, has become one of the main challenges facing
      the geriatric scientific community. The aim of the present study was to identify
      single nucleotide polymorphisms (SNPs) related to frailty. MATERIAL AND METHODS:
      The study was conducted on 152 subjects from the Toledo Study for Healthy Aging
      (65 to 95 years of age), and classified as frail (n=78), and non-frail (n=74),
      according to Fried's criteria. After blood collection, DNA was isolated and
      amplified for the analysis of SNPs using AxiomTM Genotyping technology
      (Affymetrix). Statistical analyses were performed using the Plink program and
      library SNPassoc. RESULTS: The results of the study showed 15 SNPs with a P<.001.
      Those SNPs involved in processes related to frailty, such as energy metabolism,
      regulation of biological processes, cell motility and integrity, and cognition
      are highlighted. CONCLUSIONS: These results suggest that the genetic variations
      identified in frail individuals that are involved in biological processes related
      to frailty may be considered as biomarkers for the early detection of frailty.

PMID- 29636292
TI  - [Association between dementia and pemphigoid bullous as a paradigm of a
      multidimensional and interdisciplinary attention"].

PMID- 29636293
TI  - Diagnostic value of QRS and S wave variation in patients with suspicion of acute
      pulmonary embolism.
AB  - BACKGROUND: This study aimed to investigate the diagnostic value of QRS and S
      wave variation in patients admitted to the emergency department with suspicion of
      acute pulmonary embolism (APE). METHOD: Computerized tomographic pulmonary
      angiography (CTPA) was performed in 118 consecutive patients to evaluate patients
      with suspected APE, and 106 subjects with appropriate electrocardiogram and CT
      images constituted the study population. RESULTS: Using CTPA, APE was diagnosed
      in 48.1% (n:51) of the study population. The comparison of patients with APE and
      those without APE revealed that increased heart rate, right axis deviation of QRS
      axis, complete or incomplete right bundle branch block, prominent S wave in lead
      D1, increased QRS duration, percentage of QRS (9,8[4,8-19,0] vs 3,8[2,7-71];
      p<0,001), S wave variation (22,3[9,6-31,9] vs 4,8 [2-8]; p<0,001) and DeltaS wave
      amplitude (1.1[0.5-1.5] vs 0.2[0.1-0.5]; p<0.001) were significantly associated
      with APE, but no relationship was detected with respect to the presence of atrial
      arrhythmias, clockwise rotation of the horizontal axis, fragmentation, ST segment
      deviation, T wave inversion, and S1Q3T3 and S1S2S3 patterns. The percentage of S
      wave variation (OR: 1072 per 1% increase, 95% CI:1011-1137) was found to be an
      independent predictor of APE. DeltaS wave amplitude>0.5mm predicted APE with a
      sensitivity of 72.6% and a specificity of 74.6% (AUC:0.805, 95% CI: 0.717-0.876;
      p<0.001). CONCLUSION: The present study demonstrated that QRS and S wave
      variation could be useful electrocardiographic signs for the diagnosis of APE.

PMID- 29636294
TI  - Contrast-induced encephalopathy presenting as acute subarachnoid hemorrhage.
AB  - Contrast media induced encephalopathy is a rare complication of contrast
      administration characterized by non-specific neurological signs and symptoms that
      may present both clinically and radiolographically as subarachnoid hemorrhage.
      While there are few reported presentations in the neurology literature after
      inpatient contrast administration, similar emergency department presentations
      have not been documented. We describe a patient who presented with encephalopathy
      and expressive aphasia after outpatient evaluation of an intrathecal analgesia
      pump who had radiographic imaging consistent with acute subarachnoid hemorrhage.
      The hyperdensities seen on computed tomography scanning were subsequently
      identified as residual gadolinium contrast media resulting in allergic
      encephalopathy in this patient.

PMID- 29636295
TI  - Concussion diagnoses among adults presenting to three Canadian emergency
      departments: Missed opportunities.
AB  - OBJECTIVES: Patients with concussion commonly present to the emergency department
      (ED) for assessment. Misdiagnosis of concussion has been documented in children
      and likely impacts treatment and discharge instructions. This study aimed to
      examine diagnosis of concussion in a general adult population. METHODS: Patients
      >17years old presenting meeting the World Health Organization's definition of
      concussion were recruited in one academic (Hospital 1) and two community
      (Hospitals 2 and 3) EDs in a Canadian city. A physician questionnaire and patient
      interviews documented recommendations given by emergency physicians. Bi-variable
      comparisons are reported using chi-square tests, t-tests or Mann-Whitney tests,
      as appropriate. Multivariate analyses were performed using logistic regression
      methods. RESULTS: Overall, the study enrolled 250 patients. The median age was 35
      (IQR: 23 to 49) and 52% were female. A variety of concussion causes were
      documented. Forty-one (16%) patients were not diagnosed with a concussion despite
      meeting criteria. Concussion diagnosis was less likely with a longer ED length of
      stay (OR=0.71; 95% CI: 0.60 to 0.83), presenting to the non-academic centers
      (Hospital 2: OR=0.21, 95% CI: 0.08 to 0.58; Hospital 3: OR=0.07, 95% CI: 0.02 to
      0.24), or involvement in a motor vehicle collision (OR=0.11; 95% CI: 0.03 to
      0.46). CONCLUSION: One in six patients with concussion signs and symptoms were
      misdiagnosed in the ED. Misdiagnosis was related to injury mechanism, length of
      stay, and enrolment site. Closer examination of institutional factors is needed
      to identify effective strategies to promote accurate diagnosis of concussion.

PMID- 29636296
TI  - Prevalence of current oral HPV infection among 100 betel nut chewers or cigarette
      smokers in Northern Taiwan.
AB  - BACKGROUND: The incidence of HPV positive oropharyngeal cancer is increasing in
      Taiwan. Given this, it is critical to understand the prevalence of oral HPV
      infection since this cancer is potentially preventable. A community-based study
      was conducted to evaluate the prevalence of oral HPV infection and sexual
      behavior changes. METHODS: Between January and December 2016, 100 subjects
      between 20 and 70 years-old with current/ever betel nut chewing or current
      cigarette smoking visited the Department of Health, New Taipei City. Subjects
      with cancer history or known HIV/AIDS were excluded. Sexual behavior information
      was collected through a questionnaire. Oral rinse samples and oropharyngeal swabs
      were obtained for HPV genotyping using the EasyChip HPV genotyping array (King
      Car, Taiwan). RESULTS: 92 men and 8 women were recruited. The prevalence of oral
      HPV infection was 3%, present between 60 and 70 (11%) and between 30 and 40 years
      old (4%). The prevalence of the first sexual contact at younger than 20 years old
      were 71.4%, 53.6%, 15.4% and 44% in <40, 40-49, 50-59 and 60+ years old,
      respectively (p for trend = 0.0036). The prevalence of 3 or more lifetime sexual
      partners were 60.7%, 57.1%, 23.1% and 16.7%, respectively for <40, 40-49, 50-59
      and 60+ years old (p for trend = 0.0005). CONCLUSIONS: The prevalence of oral HPV
      infection is 3%, in current/ever betel nut chewers or current cigarette smokers
      in Northern Taiwan. Younger generation have more lifetime sexual partners and
      younger first sexual contact. This could explain the rising incidence of HPV
      positive oropharyngeal cancer in Taiwan.

PMID- 29636297
TI  - Is donor age 6 years or less related to increased risk of surgical complications
      in pediatric kidney transplantation?
AB  - INTRODUCTION: Despite the widespread organ shortage dilemma, there is hesitancy
      regarding utilization of young donors (aged <=6 years) because previous reports
      have suggested that this is associated with an increased risk of surgical
      complications and graft loss. OBJECTIVE: The aim of this study was to determine
      if donor age <=6 years is related to increased risk of surgical complications or
      allograft loss in pediatric kidney transplantation (KT). STUDY DESIGN: A
      retrospective study of pediatric kidney transplants (KT) undertaken between
      January 2000 and July 2015. The incidence of surgical and urological
      complications, and allograft loss were analyzed and compared between donors aged
      <=6 years (Group 1) and donors aged >6 years (Group 2). RESULTS: A total of 171
      pediatric KTs were performed at the current center during the study period.
      Twenty-eight patients were excluded; as a result, the study comprised 143
      patients: 60 (Group 1) and 83 (Group 2). Mean recipient weight was 17 kg (SD 9.7;
      range 3.2-47) in Group 1 and 38.2 kg (SD 15.3; range 7.8-73) in Group 2. Despite
      a significantly higher proportion of risk factors in Group 1, no significant
      between-group differences were observed in terms of: surgical complications (OR
      0.4; range 0.1-1.2), early urological complications (OR 2.2; range 0.4-11), late
      urological complications (OR 0.3; range 0.8-1.4), lymphoceles (OR 6.2; range 0.7
      51.7) and allograft loss (OR 1.5; range 0.7-3.1, summary Table). Graft survival
      at 1 and 5 years was: 81% and 70% (Group 1) and 92% and 79% (Group 2),
      respectively (P = 0.093). Mean follow-up was 90.13 +/- 49.7 months. DISCUSSION:
      The main finding of this retrospective study was that pediatric donor kidneys
      from donors aged <=6 years could safely be used in pediatric recipients without
      an increased risk of surgical and urological complications or graft loss.
      Nevertheless, KT with small donor kidneys is challenging and should be performed
      at experienced pediatric centers. CONCLUSION: In line with these results, the
      outcomes of KT using donors aged <=6 years were encouraging and similar to those
      obtained with older donors. Thus, this study supported using kidney grafts from
      young donors, given the organ shortage and potential high mortality risk while
      awaiting KT.

PMID- 29636298
TI  - Role of surgery in localized initially unresectable neuroblastoma.
AB  - PURPOSE: Evaluating the role of surgery and the extent of tumor resection on the
      outcome of patients with localized initially unresectable neuroblastoma (NB).
      PATIENTS AND METHODS: This was a retrospective case review study including
      patients with localized initially unresectable NB. The primary tumor was
      considered unresectable according to imaging defined risk factors (IDRFs).
      Surgical resection was attempted after four to six courses of chemotherapy. The
      extent of resection was classified as follows: >=90% resection, incomplete
      resection (50-90%) and cases with <50% resection or just a biopsy. Survival
      analysis was performed using an intention-to-treat approach. RESULTS: A total of
      202 patients with NB were included. Surgical resection was done in 106 patients.
      It was >=90% in 89 patients (83.9%). Surgical resection was not performed in 96
      patients (47.5%). Fifty-five (57.2%) were in good response after primary
      chemotherapy and 41 patients (42.7%) had persisting IDRFs, nine of them had
      biopsy only, and a follow-up strategy was considered in the other 32 patients.
      The overall 5-year event-free survival (EFS) and overall survival (OS) were 89.1
      +/- 2.4% and 94.9 +/- 1.7%, respectively, with significantly better OS and EFS
      for patients who had resection versus no resection (p = 0.003 and 0.04,
      respectively). There was no impact of extent of resection on EFS and OS in the
      whole group (p = 0.91, p = 0.9) and in subgroup analysis stratified by site,
      histology, and age of the patients. CONCLUSION: In children with localized
      initially unresectable NB, surgical resection was the only significant risk
      factor associated with better survival. The extent of tumor resection had no
      impact on EFS and OS. The concept of accepting incomplete resection to avoid
      serious complications was successful.

PMID- 29636299
TI  - Outstanding impact of soil tillage on the abundance of soil hydrolases revealed
      by a metagenomic approach.
AB  - The soil represents the main source of novel biocatalysts and biomolecules of
      industrial relevance. We searched for hydrolases in silico in four shotgun
      metagenomes (4,079,223 sequences) obtained in a 13-year field trial carried out
      in southern Brazil, under the no-tillage (NT), or conventional tillage (CT)
      managements, with crop succession (CS, soybean/wheat), or crop rotation (CR,
      soybean/maize/wheat/lupine/oat). We identified 42,631 hydrolases belonging to
      five classes by comparing with the KEGG database, and 44,928 sequences by
      comparing with the NCBI-NR database. The abundance followed the order:
      lipases>laccases>cellulases>proteases>amylases>pectinases. Statistically
      significant differences were attributed to the tillage system, with the NT
      showing about five times more hydrolases than the CT system. The outstanding
      differences can be attributed to the management of crop residues, left on the
      soil surface in the NT, and mechanically broken and incorporated into the soil in
      the CT. Differences between the CS and the CR were slighter, 10% higher for the
      CS, but not statistically different. Most of the sequences belonged to fungi
      (Verticillium, and Colletotrichum for lipases and laccases, and Aspergillus for
      proteases), and to the archaea Sulfolobus acidocaldarius for amylases. Our
      results indicate that agricultural soils under conservative managements may
      represent a hotspot for bioprospection of hydrolases.

PMID- 29636301
TI  - Transseptal transcatheter mitral valve-in-valve for treatment of severe mitral
      regurgitation in failed bioprosthesis complicated with cardiogenic shock: Case
      report and review of the literature.
AB  - Patients in cardiogenic shock due to severe failure of a mitral bioprosthesis
      have extremely high risk for repeat standard cardiac surgery. This patient
      population may benefit the most form the least invasive intervention. We report a
      successful transseptal mitral valve-in-valve implant performed in a patient in
      cardiogenic shock due to a flail mitral bioprosthesis requiring bridging
      intravenous inotropic and intra-aortic balloon pump support.

PMID- 29636300
TI  - Prognostic Value of ACVRL1 Expression in Metastatic Colorectal Cancer Patients
      Receiving First-line Chemotherapy With Bevacizumab: Results From the Triplet Plus
      Bevacizumab (TRIBE) Study.
AB  - BACKGROUND: No biomarkers exist to predict benefit from antiangiogenic therapy in
      metastatic colorectal cancer patients. ACVRL1 (activin receptor like-protein 1)
      encodes for ALK1, a member of the transforming growth factor-beta receptor
      family, which directs pathologic angiogenesis. We examined the intratumoral
      expression of ACVRL1 and other angiogenesis pathway-related genes to identify
      molecular markers in the TRIBE study. MATERIALS AND METHODS: Of 503 randomized
      patients, 228 had sufficient tissue for analysis. Formalin-fixed paraffin
      embedded specimens were examined for expression of VEGF-A, VEGF-B, VEGF-C,
      VEGFR1, VEGFR2, ACVRL1, EphB4, and EGFL7 using reverse transcription polymerase
      chain reaction. A maximal chi2 approach was used to determine the messenger RNA
      levels associated with progression-free survival (PFS), overall survival (OS),
      response rate, early tumor shrinkage, and depth of response. Recursive
      partitioning trees were constructed to identify composite prognostic biomarker
      profiles. External validation was conducted in silico using the Oncomine
      database. RESULTS: High ACVRL1 expression was associated with superior OS in both
      treatment arms (FOLFOXIRI [5-fluorouracil, leucovorin, oxaliplatin, irinotecan]
      bevacizumab, 32.7 vs. 13.5 months, hazard ratio [HR], 0.38, P = .023; FOLFIRI [5
      fluorouracil, leucovorin, irinotecan]-bevacizumab, 35.1 vs. 22.0 months, HR,
      0.36, P = .006) and prolonged PFS (11.7 vs. 5.9 months, multivariate HR, 0.17; P
      = .001) for patients receiving FOLFOXIRI-bevacizumab on univariate and
      multivariate analyses. In recursive partitioning analysis, ACVRL1 was the
      strongest discriminator of the response rate, PFS, and OS in patients receiving
      FOLFOXIRI-bevacizumab and of OS in patients receiving FOLFIRI-bevacizumab. In
      silico validation revealed significant associations between ACVRL1 expression,
      disease recurrence, and 1-year survival (P < .05) among all colorectal cancer
      stages. CONCLUSION: ACVRL1 expression could serve as a prognostic biomarker in
      metastatic colorectal cancer patients receiving chemotherapy and bevacizumab and
      warrants further evaluation in prospective studies.

PMID- 29636302
TI  - Assessment of clinical outcomes of advanced hilar cholangiocarcinoma.
AB  - BACKGROUND: Low resectability and poor survival outcome are common for hilar
      cholangiocarcinoma (HCCA), especially in advanced stages. The present study was
      to assess the clinical outcome of advanced HCCA, focusing on therapeutic
      modalities, survival analysis and prognostic assessment. METHODS: Clinical data
      of 176 advanced HCCA patients who had been treated in our hospital between
      January 2013 and December 2015 were analyzed retrospectively. Prognostic effects
      of clinicopathological factors were explored by univariate and multivariate
      analysis. Survival predictors were evaluated by the receiver operating
      characteristic (ROC) curve. RESULTS: The 3-year overall survival rate was 13% for
      patients with advanced HCCA. Preoperative total bilirubin (P = 0.009), hepatic
      artery invasion (P = 0.014) and treatment modalities (P = 0.020) were independent
      prognostic factors on overall survival. A model combining these independent
      prognostic factors (area under ROC curve: 0.748; 95% CI: 0.678-0.811;
      sensitivity: 82.3%, specificity: 53.5%) was highly predictive of tumor death.
      After R0 resection, the 3-year overall survival was up to 38%. Preoperative total
      bilirubin was still an independent negative factor, but not for hepatic artery
      invasion. CONCLUSIONS: Surgery is still the best treatment for advanced HCCA.
      Preoperative biliary drainage should be performed in highly-jaundiced patients to
      improve survival. Prediction of survival is improved significantly by a model
      that incorporates preoperative total bilirubin, hepatic artery invasion and
      treatment modalities.

PMID- 29636303
TI  - Effect of flexibility deficit on scapular asymmetry in individuals with and
      without shoulder pain.
AB  - BACKGROUND: Many studies have investigated the relationship between soft tissue
      tightness and shoulder kinematics. However, there is a lack of information on the
      dynamic properties responsible for side-to-side differences such as scapular
      asymmetry. OBJECTIVE: To determine the relationship between a deficit in soft
      tissue flexibility and scapular asymmetry. METHODS: A total of 58 individuals (29
      patients with shoulder pain and 29 asymptomatic participants) were enrolled.
      Bilateral shortening of the pectoralis minor muscle and posterior shoulder
      tightness were assessed. Additionally, side-to-side flexibility deficit was
      calculated. Scapular kinematics were measured with an electromagnetic tracking
      device while individuals were standing in a resting position and during arm
      elevation. The symmetry angle was calculated to quantify scapular asymmetry.
      RESULTS: The pectoralis minor and the posterior capsule flexibility deficit
      showed a significant positive relationship with the symmetry angle in the resting
      position separately for both asymptomatic (r=0.47, r=0.37 relatively) and
      symptomatic groups (r=0.58, r=0.38 relatively), indicating that the increased
      deficit in the pectoralis minor and posterior capsule flexibility were associated
      with increased scapular asymmetry. However, no significant relationship was found
      between flexibility deficit and scapular asymmetry during arm elevation and
      lowering for both asymptomatic and symptomatic groups. CONCLUSION: The findings
      of the study provided information on the relationship of a flexibility deficit on
      the scapular position and orientation in asymptomatic and symptomatic
      populations.

PMID- 29636304
TI  - Prevalence of knee osteoarthritis in former athletes: a systematic review with
      meta-analysis.
AB  - BACKGROUND: Prevalence of knee osteoarthritis in former athletes is still
      unclear. OBJECTIVE: To investigate prevalence of knee osteoarthritis in former
      athletes. Moreover, the secondary aim was to investigate whether poor
      methodological quality of included studies, different diagnosis criteria for knee
      osteoarthritis, different sports modality or sex impact on overall estimated
      prevalence of knee osteoarthritis in former athletes. METHODS: Searches on
      MEDLINE, EMBASE, AMED, SPORTDiscus and CINAHL from the earliest record to
      February 2018 and hand-searching identified studies investigating prevalence of
      knee osteoarthritis in former athletes. Meta-analysis was conducted and the GRADE
      system summarized strength of the current recommendations. Sensitivity analyses
      investigated whether methodological quality, diagnostic criteria, type of sports
      or sex impacted on the overall estimated prevalence in former athletes. This
      review was registered at PROSPERO (CRD42016050903). RESULTS: Fifteen studies were
      included and pooling of 3100 participants estimated overall prevalence of knee
      osteoarthritis in former athletes of 30.0% (95% CI: 20.0 to 40.0%). The strength
      of the current recommendations was low-quality. Sensitivity analyses suggested
      that different diagnostic criteria for knee osteoarthritis and type of sports may
      impact on the overall estimated prevalence. CONCLUSIONS: Prevalence of knee
      osteoarthritis in former athletes was 30.0%. Researchers, clinicians and
      policymakers should be careful about potential prevalence differences among type
      of sports and diagnostic criteria. Current low-quality evidence shows that future
      high-quality studies are likely to impact on the estimated prevalence.

PMID- 29636305
TI  - Effects of inspiratory muscle training in children with cerebral palsy: a
      randomized controlled trial.
AB  - BACKGROUND: Respiratory muscle weakness and its relation to other impairments in
      children with cerebral palsy (CP) have been shown in the latest studies. The
      effects of inspiratory muscle training (IMT) in this population have not been
      comprehensively investigated so far. OBJECTIVES: To investigate the effects of
      IMT on trunk control, pulmonary functions, respiratory muscle strength, daily
      living activities, exercise capacity and quality of life in children with CP.
      METHODS: This was a prospective-randomized controlled trial. Twenty-five children
      with CP were randomly assigned to the treatment (n=13) or the control group
      (n=12). The treatment group received IMT at 30% of maximal inspiratory pressure
      (MIP) and the control group received sham therapy (5% of MIP) for 6 weeks. Also,
      both groups received routine conventional physical therapy (stretching,
      strengthening, and functional exercises, etc.) for 6 weeks. The primary outcome
      measure was trunk control. Secondary outcome measures were pulmonary function,
      respiratory muscle strength, daily living activities, functional exercise
      capacity and quality of life. RESULTS: The treatment group had better outcome for
      trunk control (3.87, 95% CI 3.72-4.02). Also, respiratory muscle strength, daily
      living activities, functional exercise capacity and quality of life were
      significantly improved in the treatment group compared with controls. No
      improvements were observed in the pulmonary function test scores between the
      groups. CONCLUSION: Inspiratory muscle training improves trunk control,
      respiratory muscle strength, daily living activities, functional exercise
      capacity and quality of life in children with CP and it can be included in the
      physiotherapy and rehabilitation programs.

PMID- 29636307
TI  - Three-dimensional evaluation of mandibular asymmetry: a new classification and
      three-dimensional cephalometric analysis.
AB  - Mandibular asymmetry is common among orthognathic patients and exhibits great
      variation. The aim of this study was to propose a new classification of
      mandibular asymmetry by anatomical regions; namely R (ramus), B (mandibular body)
      and C (chin), in conjunction with a corresponding 'RBC' three-dimensional (3D)
      cephalometric analysis. The cone beam computed tomography data of 65 patients
      with mandibular asymmetry was retrieved to perform the RBC 3D cephalometric
      analysis and to investigate the characteristics of mandibular asymmetry. It was
      found that the more posteriorly in mandible, the more pronounced was the vertical
      asymmetry. Significant transverse asymmetry was only noted in mandibular body.
      Both mandibular body and chin were significantly asymmetric in length. Seven
      significant morphologic predictors of menton deviation were identified, namely
      lower dental midline shift, difference in ramus height, difference in chin
      length, difference in body length, body height on contralateral side, coronoid
      height on deviated side and body width on contralateral side, confirming the
      complex nature of mandibular asymmetry. This simple and concise classification
      allows comprehensive assessment of mandible morphology by anatomical regions
      which also facilitates diagnosis, treatment planning and communication in both
      clinical and research settings.

PMID- 29636306
TI  - Dual-task as a predictor of falls in older people with mild cognitive impairment
      and mild Alzheimer's disease: a prospective cohort study.
AB  - BACKGROUND: A dual-task tool with a challenging and daily secondary task, which
      involves executive functions, could facilitate the screening for risk of falls in
      older people with mild cognitive impairment or mild Alzheimer's disease.
      OBJECTIVE: To verify if a motor-cognitive dual-task test could predict falls in
      older people with mild cognitive impairment or mild Alzheimer's disease, and to
      establish cutoff scores for the tool for both groups. METHODS: A prospective
      study was conducted with community-dwelling older adults, including 40 with mild
      cognitive impairment and 38 with mild Alzheimer's disease. The dual-task test
      consisted of the Timed up and Go Test associated with a motor-cognitive task
      using a phone to call. Falls were recorded during six months by calendar and
      monthly telephone calls and the participants were categorized as fallers or non
      fallers. RESULTS: In the Mild cognitive impairment Group, fallers presented
      higher values in time (35.2s), number of steps (33.7 steps) and motor task cost
      (116%) on dual-task compared to non-fallers. Time, number of steps and motor task
      cost were significantly associated with falls in people with mild cognitive
      impairment. Multivariate analysis identified higher number of steps spent on the
      test to be independently associated with falls. A time greater than 23.88s
      (sensitivity=80%; specificity=61%) and a number of steps over 29.50
      (sensitivity=65%; specificity=83%) indicated prediction of risk of falls in the
      Mild cognitive impairment Group. Among people with Alzheimer's disease, no
      differences in dual-task between fallers and non-fallers were found and no
      variable of the tool was able to predict falls. CONCLUSION: The dual-task
      predicts falls only in older people with mild cognitive impairment.

PMID- 29636308
TI  - A novel digital workflow to manufacture personalized three-dimensional-printed
      hollow surgical obturators after maxillectomy.
AB  - Partial or complete resection of the maxilla during tumour surgery causes
      oronasal defects, leading to oral-maxillofacial dysfunction, for which the
      surgical obturator (SO) is an important treatment option. Traditional
      manufacturing of SOs is complex, time-consuming, and often results in inadequate
      fit and function. This technical note describes a novel digital workflow to
      design and manufacture a three-dimensional (3D)-printed hollow SO. Registered
      computed tomography and magnetic resonance imaging images are used for gross
      tumour delineation. The produced RTStruct set is exported as a stereolitography
      (STL) file and merged with a 3D model of the dental status. Based on these merged
      files, a personalized and hollow digital SO design is created, and 3D printed.
      Due to the proper fit of the prefabricated SO, a soft silicone lining material
      can be used during surgery to adapt the prosthesis to the oronasal defect,
      instead of putty materials that are not suitable for this purpose. An STL file of
      this final SO is created during surgery, based on a scan of the relined SO. The
      digital workflow results in a SO weight reduction, an increased fit, an up-to
      date digital SO copy, and overall easier clinical handling.

PMID- 29636310
TI  - L-Cysteine Partially Protects Against Acrylamide-Induced Testicular Toxicity.
AB  - BACKGROUND: Acrylamide is a widespread substance having many areas of
      utilization. Besides, it also forms a part of high-temperature processed starchy
      foods. To date, numerous in vivo and in vitro studies have documented that
      acrylamide has toxic effects on various organ systems. AIMS: To determine the
      potential protective effect of L-cysteine on acrylamide-induced testicular
      toxicity. STUDY DESIGN: Animal experimentation. METHODS: We randomly divided 28
      rats into four groups as control (0.9% saline), L-cysteine (150 mg/kg),
      acrylamide (40 mg/kg) and acrylamide + L-cysteine. After a 10-day intraperitoneal
      injection period, we euthanized the animals, recorded their body and testis
      weights, collected blood samples for serum testosterone measurement, and excised
      testes for histopathological and morphometric evaluation. Besides,
      immunohistochemical scoring of proliferating cell nuclear antigen and bax
      proteins was performed. RESULTS: Acrylamide reduced body (p<0.01) and testis
      weights (p<0.05), seminiferous tubule diameter (p<0.001) and proliferating cell
      nuclear antigen expression (p<0.05), while it increased bax protein expression
      (p<0.01) and the percentage of seminiferous tubules that contain multinucleated
      giant cells (p<0.001), but did not significantly change serum testosterone levels
      when compared to control. L-cysteine administered with acrylamide decreased
      multinucleated giant cell number (p<0.001) and reversed the reduced proliferating
      cell nuclear antigen positivity (p<0.001), but did not restore other parameters
      compared with the acrylamide alone-treated group. CONCLUSION: Taking into account
      the dose and duration employed, the present study concluded that L-cysteine
      partially protects testis against acrylamide-induced toxic effects.

PMID- 29636309
TI  - Topical vapocoolant spray reduces nociceptive response to ear notching in
      neonatal piglets.
AB  - OBJECTIVE: To evaluate the efficacy of a vapocoolant spray (VS) to provide local
      anaesthesia for piglets during ear notching. STUDY DESIGN: Randomized study.
      ANIMALS: Eleven 10 day old and forty 3-5 day old Large White piglets. METHODS:
      Temperature validation studies using thermocouples and a temperature data logger
      were conducted on dead and live tissue to determine optimal spray distance and
      duration to reduce tissue temperature to below 10  degrees C. A behavioural trial
      was conducted to assess efficacy for ear notching. Piglets were randomly assigned
      to one of four treatment groups: positive control (POS; n = 10), VS (n = 10),
      lignocaine (LIG; n = 10) and negative control (NEG; n = 10). Spray was
      administered to the margin of each ear, from a distance of 10 cm, and for a
      duration of 2 seconds immediately prior to ear notching. Behavioural observation
      was used to assess movement and vocal response, with responses categorized as no
      response (0) and response (1). RESULTS: Temperature and tissue validation studies
      indicated that a 2 second spray from 10 cm reduced tissue temperature to below 10
      degrees C, and reduced response to stimulation of the skin with an 18 gauge
      needle (p < 0.001). There was a significant effect of treatment on response to
      ear notching (p < 0.001). The probability of a piglet to respond to ear notching
      was 98.7% for NEG piglets, compared with those treated with VS (5.3%), LIG (1.1%)
      and sham-notched piglets (0.9%). CONCLUSIONS AND CLINICAL RELEVANCE: This study
      contributes new data on the pain of ear notching in piglets. The application of a
      topical VS prior to ear notching reduced the antinociceptive response of piglets
      to the procedure, similar to that of a local anaesthetic. Cryoanaesthesia
      presents a simple and effective option for reducing the pain response to this
      simple husbandry procedure.

PMID- 29636311
TI  - Polypropylene Suture Guided Microdochectomy for Pathologic Nipple Discharge

PMID- 29636312
TI  - The Role of Follicular Fluid Thiol/Disulphide Homeostasis in Polycystic Ovary
      Syndrome
AB  - BACKGROUND: Oxidative stress has been proposed as a potential trigger in the
      etiopathogenesis of polycystic ovary syndrome-related infertility.
      Thiol/disulphide homeostasis, a recently identified oxidative stress marker, is
      one of the antioxidant mechanism in humans with critical roles in
      folliculogenesis and ovulation. AIMS: To investigate follicular fluid
      thiol/disulphide homeostasis in the etiopathogenesis of polycystic ovary syndrome
      and to determine its association with in vitro fertilization outcome. The study
      procedures were approved by the local ethics committee. STUDY DESIGN: Cross
      sectional study. Methods: Follicular fluid from 22 women with polycystic ovary
      syndrome and 20 ovulatory controls undergoing in vitro fertilization treatment
      was sampled. Thiol/disulphide homeostasis was analyzed via a novel
      spectrophotometric method. Results: Follicular native thiol levels, as well as
      the native thiol/total thiol ratio, were lower in the polycystic ovary syndrome
      group than in the non-polycystic ovary syndrome group (p=0.041 and p<0.0001,
      respectively). Disulphide levels, disulphide/native thiol, and disulphide/total
      thiol ratios were increased in the polycystic ovary syndrome group (p<0.0001). A
      positive correlation between the fertilization rate and native thiol (p=0.01,
      r=0.53) and total thiol (p=0.01, r=0.052) among polycystic ovary syndrome
      patients was found. A positive predictive effect of native thiol level on the
      fertilization rate in the polycystic ovary syndrome group was also found (p=0.03,
      beta=0.45, 95% CI= 0.031-0.643). Conclusion: Deterioration of thiol/disulphide
      homeostasis, especially elevated disulphide levels, could be one of the
      etiopathogenetic mechanisms in polycystic ovary syndrome. Increased native thiol
      levels are related to the fertilization rate among polycystic ovary syndrome
      patients and are positive predictors of the fertilization rate among polycystic
      ovary syndrome patients. Improvement of thiol/disulphide homeostasis could be
      important in the treatment of polycystic ovary syndrome to increase in vitro
      fertilization success.

PMID- 29636313
TI  - Outcome after prenatal diagnosis of fetal urinary tract abnormalities: A tertiary
      center experience
AB  - Objective: With the widespread use of ultrasonography for fetal screening, the
      detection and management of congenital urinary tract abnormalities has become
      crucial. In this study, we aimed to describe the clinical approaches in patients
      with prenatally detected urinary tract abnormalities. Material and Methods: This
      study is a retrospective, single-center study performed at a perinatology unit of
      a university hospital, between 2010 and 2016. The outcomes of 124 patients who
      were prenatally diagnosed as having urinary tract abnormalities are reported.
      Variables included in the analysis were fetal sex, birth week and weight,
      persistency, and necessity surgery after birth for renal pelvic dilatation. Low
      risk renal pelvic dilatation was determined as an anterior-posterior (AP)
      diameter of 4-7 mm at 16-28 weeks, 7-10 mm after 28 weeks, whereas high-risk
      dilatation was defined as AP measurements of >=7 mm at 16-28 weeks, >=10 mm after
      28 weeks, respectively. Results: The majority of patients consisted of male
      fetuses with bilateral pelviectasis (62.9%, 20.2%, respectively). The mean age
      was 28.8+/-6.4 years. The mean gestational age at birth was 34.2+/-7.8 weeks. The
      mean birth weight was 2593+/-1253.3 g. The need for surgery was greater in high
      risk patients than in low-risk patients (58.3% vs. 8.7%) (p<0.002). Conclusion:
      Patients with high-risk antenatal renal pelvic dilatation require surgical
      treatment after delivery. Close prenatal and postnatal follow-up is mandatory in
      specialized centers. Perinatologists, neonatologists, pediatricians and pediatric
      nephrologists, and radiologists should treat these children with a
      multidisciplinary approach.

PMID- 29636314
TI  - Congenital Spigelian Hernia Combined with Bilateral Inguinal Hernias

PMID- 29636315
TI  - Multidisciplinary Collaboration in the Treatment of Patients With Type 2 Diabetes
      in Primary Care: Analysis Using Process Mining.
AB  - BACKGROUND: Public health in several countries is characterized by a shortage of
      professionals and a lack of economic resources. Monitoring and redesigning
      processes can foster the success of health care institutions, enabling them to
      provide a quality service while simultaneously reducing costs. Process mining, a
      discipline that extracts knowledge from information system data to analyze
      operational processes, affords an opportunity to understand health care
      processes. OBJECTIVE: Health care processes are highly flexible and
      multidisciplinary, and health care professionals are able to coordinate in a
      variety of different ways to treat a diagnosis. The aim of this work was to
      understand whether the ways in which professionals coordinate their work affect
      the clinical outcome of patients. METHODS: This paper proposes a method based on
      the use of process mining to identify patterns of collaboration between
      physician, nurse, and dietitian in the treatment of patients with type 2 diabetes
      mellitus and to compare these patterns with the clinical evolution of the
      patients within the context of primary care. Clustering is used as part of the
      preprocessing of data to manage the variability, and then process mining is used
      to identify patterns that may arise. RESULTS: The method is applied in three
      primary health care centers in Santiago, Chile. A total of seven collaboration
      patterns were identified, which differed primarily in terms of the number of
      disciplines present, the participation intensity of each discipline, and the
      referrals between disciplines. The pattern in which the three disciplines
      participated in the most equitable and comprehensive manner had a lower
      proportion of highly decompensated patients compared with those patterns in which
      the three disciplines participated in an unbalanced manner. CONCLUSIONS: By
      discovering which collaboration patterns lead to improved outcomes, health care
      centers can promote the most successful patterns among their professionals so as
      to improve the treatment of patients. Process mining techniques are useful for
      discovering those collaborations patterns in flexible and unstructured health
      care processes.

PMID- 29636316
TI  - Harnessing Reddit to Understand the Written-Communication Challenges Experienced
      by Individuals With Mental Health Disorders: Analysis of Texts From Mental Health
      Communities.
AB  - BACKGROUND: Mental disorders such as depression, bipolar disorder, and
      schizophrenia are common, incapacitating, and have the potential to be fatal.
      Despite the prevalence and gravity of mental disorders, our knowledge concerning
      everyday challenges associated with them is relatively limited. One of the most
      studied deficits related to everyday challenges is language impairment, yet we do
      not know how mental disorders can impact common forms of written communication,
      for example, social media. OBJECTIVE: The aims of this study were to investigate
      written communication challenges manifest in online mental health communities
      focusing on depression, bipolar disorder, and schizophrenia, as well as the
      impact of participating in these online mental health communities on written
      communication. As the control, we selected three online health communities
      focusing on positive emotion, exercising, and weight management. METHODS: We
      examined lexical diversity and readability, both important features for measuring
      the quality of writing. We used four well-established readability metrics that
      consider word frequencies and syntactic complexity to measure writers' written
      communication ability. We then measured the lexical diversity by calculating the
      percentage of unique words in posts. To compare lexical diversity and readability
      among communities, we first applied pairwise independent sample t tests, followed
      by P value adjustments using the prespecified Hommel procedure to adjust for
      multiple comparison. To measure the changes, we applied linear least squares
      regression to the readability and lexical diversity scores against the
      interaction sequence for each member, followed by pairwise independent sample t
      tests and P value adjustments. Given the large sample of members, we also report
      effect sizes and 95% CIs for the pairwise comparisons. RESULTS: On average,
      members of depression, bipolar disorder, and schizophrenia communities showed
      indications of difficulty expressing their ideas compared with three other online
      health communities. Our results also suggest that participating in these
      platforms has the potential to improve members' written communication. For
      example, members of all three mental health communities showed statistically
      significant improvement in both lexical diversity and readability compared with
      members of the OHC focusing on positive emotion. CONCLUSIONS: We provide new
      insights into the written communication challenges faced by individuals suffering
      from depression, bipolar disorder, and schizophrenia. A comparison with three
      other online health communities suggests that written communication in mental
      health communities is significantly more difficult to read, while also consisting
      of a significantly less diverse lexicon. We contribute practical suggestions for
      utilizing our findings in Web-based communication settings to enhance members'
      communicative experience. We consider these findings to be an important step
      toward understanding and addressing everyday written communication challenges
      among individuals suffering from mental disorders.

PMID- 29636317
TI  - Women's Perceptions of Using Mobile Phones for Maternal and Child Health Support
      in Afghanistan: Cross-Sectional Survey.
AB  - BACKGROUND: Growing rates of global mobile subscriptions pave the way for
      implementation of mobile health (mHealth) initiatives, especially among hard-to
      reach populations. OBJECTIVE: This study aimed to determine the perceptions of
      Afghan women regarding the use of mobile phones for maternal and child health
      services. METHODS: A cross-sectional survey was conducted in both rural and urban
      districts of Nangarhar Province, Afghanistan. The interviewer-administered
      questionnaire was used to assess participants' demographic profile, mobile phone
      usage, and perception of respondents toward different aspects of health care
      delivery via mobile phones. RESULTS: Of the 240 participants, 142 (59.2%) owned
      mobile phones and 220 (91.7%) routinely used mobile phones. Approximately 209
      (87.1%) of participants were willing to receive health messages via a mobile
      phone. Automated voice call was the most preferred method for sending health
      messages. More than 90% of the women reported that they would like to receive
      reminders for their children's vaccinations and antenatal care visits.
      CONCLUSIONS: Users' perception was associated with mobile phone ownership,
      literacy level, and experience using mobile phones. In the study area, where the
      literacy rate is low, mHealth was well perceived.

PMID- 29636318
TI  - Predicting Sexual Behaviors Among Homeless Young Adults: Ecological Momentary
      Assessment Study.
AB  - BACKGROUND: Homeless youth continue to be disproportionately affected by HIV
      compared with their housed peers, with prevalence rates as high as 13%. Yet, HIV
      prevention in this high-risk population has been only marginally effective.
      OBJECTIVE: The aim of this study was to use ecological momentary assessments to
      examine real-time factors to determine the predictors of sexual activity among
      homeless youth. METHODS: Youth experiencing homelessness aged between 18 and 24
      years were recruited from a drop-in center in Houston, Texas, between August 2015
      and May 2016. All the participants received a study-issued mobile phone that
      prompted brief ecological momentary assessments (EMAs) 5 times a day for 21 days.
      EMA items assessed near real-time sexual behaviors, cognitions, stress, affect,
      environmental factors, and environmental circumstances. RESULTS: Participants
      (N=66) were predominantly male (41/66, 64%) and black (43/66, 66%) with a median
      age of 20 years. The mean number of EMAs completed by each participant was 45 out
      of 105 possible observations. During the study, 70% (46/66) of participants were
      sexually active and reported condomless sex in 102 of the 137 cases of sexual
      intercourse (74.5%). In total, 82% (38/46) of the youth who reported having sex
      during the 3 weeks of data collection also reported engaging in high-risk sexual
      activities, including having condomless sex (24/46, 53%), having multiple sexual
      partners on the same day (12/46, 26%), trading sex (7/46, 16%), and sharing
      needles while injecting drugs (1/46, 3%). Of those, 71% (27/38) were engaged in
      multiple sexual risk behaviors. The predictive model was based on observations
      from 66 subjects who reported 137 cases of sexual intercourse over 811 days;
      sexual orientation, race, mental health, drug use, and sexual urge were included
      as predictors in the parsimonious generalized linear mixed model selected on the
      basis of the Akaike information criterion. The estimated odds ratios (ORs) were
      notable for same-day drug use (OR 2.17, 95% CI 4.48-17.31; P<.001) and sexual
      urge (OR 1.44, 95% CI 1.60-11.28; P=.004). The performance of the risk estimator
      was satisfactory, as indicated by the value of 0.834 for the area under the
      receiver operating characteristic curve. CONCLUSIONS: Real-time EMA data can be
      used to predict sexual intercourse among a sample of high-risk, predominately
      unsheltered homeless youth. Sexual urge and drug use accounts for increased odds
      of engaging in sexual activity on any given day. Interventions targeting sexual
      urge and drug use may help predict sexual activity among a population at high
      risk of HIV.

PMID- 29636319
TI  - Mobile Phone Support for Diabetes Self-Care Among Diverse Adults: Protocol for a
      Three-Arm Randomized Controlled Trial.
AB  - BACKGROUND: Nonadherence to self-care is common among patients with type 2
      diabetes (T2D) and often leads to severe complications. Moreover, patients with
      T2D who have low socioeconomic status and are racial/ethnic minorities
      disproportionately experience barriers to adherence and poor outcomes. Basic
      phone technology (text messages and phone calls) provides a practical medium for
      delivering content to address patients' barriers to adherence; however, trials
      are needed to explore long-term and sustainable effects of mobile phone
      interventions among diverse patients. OBJECTIVE: The aim of this study is to
      evaluate the effects of mobile phone-based diabetes support interventions on self
      care and hemoglobin A1c (HbA1c) among adults with T2D using a 3-arm, 15-month
      randomized controlled trial with a Type 1 hybrid effectiveness-implementation
      approach. The intervention arms are (1) Rapid Encouragement/Education And
      Communications for Health (REACH) and (2) REACH + Family-focused Add-on for
      Motivating Self-care (FAMS). METHODS: We recruited primary care patients with T2D
      (N=512) from Federally Qualified Health Centers and an academic medical center,
      prioritizing recruitment of publicly insured and minority patients from the
      latter. Eligible patients were prescribed daily diabetes medication and owned a
      cell phone with text messaging capability. We excluded patients whose most recent
      HbA1c result within 12 months was <6.8% to support detection of intervention
      effects on HbA1c. Participants were randomly assigned to REACH only, REACH +
      FAMS, or the control condition. REACH provides text messages tailored to address
      patient-specific barriers to medication adherence based on the Information
      Motivation-Behavioral skills model, whereas FAMS provides monthly phone coaching
      with related text message content focused on family and friend barriers to diet
      and exercise adherence. We collect HbA1c and self-reported survey data at
      baseline and at 3, 6, and 12 months, and again at 15 months to assess sustained
      changes. We will use generalized estimating equation models to test the effects
      of REACH (either intervention arm) on HbA1c relative to the control group, the
      potential additive effects of FAMS, and effects of either intervention on
      adherence to self-care behaviors and diabetes self-efficacy. RESULTS: The trial
      is ongoing; recruitment closed December 2017. We plan to perform analyses on 6
      month outcomes for FAMS in July 2018, and project to have 15-month data for REACH
      analyses in April 2019. CONCLUSIONS: Our study will be one of the first to
      evaluate a long-term, theory-based text messaging intervention to promote self
      care adherence among racially/ethnically and socioeconomically diverse adults
      with T2D. Moreover, our study will assess the feasibility of a family-focused
      intervention delivered via mobile phones and compare the effects of text
      messaging alone versus text messaging plus phone coaching. Findings will advance
      our understanding of how interventions delivered by phone can benefit diverse
      patients with chronic conditions. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT02409329; https://clinicaltrials.gov/ct2/show/NCT02409329 (Archived by WebCite
      at http://www.webcitation.org/6yHkg9SSl); NCT02481596;
      https://clinicaltrials.gov/ct2/show/NCT02481596 (Archived by WebCite at
      http://www.webcitation.org/6yHkj9XD4).

PMID- 29636321
TI  - Evaluating the Effectiveness of Text Messaging and Phone Call Reminders to
      Minimize No Show at Pediatric Outpatient Clinics in Pakistan: Protocol for a
      Mixed-Methods Study.
AB  - BACKGROUND: Missing health care appointments without canceling in advance results
      in a no show, a vacant appointment slot that cannot be offered to others. No show
      can be reduced by reminding patients about their appointment in advance. In this
      regard, mobile health (mHealth) strategy is to use text messaging (short message
      service, SMS), which is available on all cellular phones, including cheap low-end
      handsets. Nonattendance for appointments in health care results in wasted
      resources and disturbs the planned work schedules. OBJECTIVES: The purpose of
      this study is to evaluate the efficacy of the current text messaging (SMS) and
      call-based reminder system and further explore how to improve the attendance at
      the pediatric outpatient clinics. The primary objectives are to (1) determine the
      efficacy of the current clinic appointment reminder service at pediatric
      outpatient clinics at Aga Khan University Hospital, (2) assess the mobile phone
      access and usage among caregivers visiting pediatrics consultant clinics, and (3)
      explore the perception and barriers of parents regarding the current clinic
      appointment reminder service at the pediatric outpatient clinics at Aga Khan
      University Hospital. METHODS: The study uses a mixed-method design that consists
      of 3 components: (1) retrospective study (component A) which aims to determine
      the efficacy of text messaging (SMS) and phone call-based reminder service on
      patient's clinic attendance during January to June 2017 (N=58,517); (2)
      quantitative (component B) in which a baseline survey will be conducted to assess
      the mobile phone access and usage among parents/caregivers of children visiting
      pediatrics consultant clinics (n=300); and (3) qualitative (component C) includes
      in-depth interviews and focus group discussion with parents/caregivers of
      children visiting the pediatric consultancy clinic and with health care providers
      and administrative staff. Main constructs will be to explore perceptions and
      barriers related to existing clinic appointment reminder service. Ethics approval
      has been obtained from the Ethical Review Committee, Aga Khan University,
      Pakistan (4770-Ped-ERC-17). RESULTS: Results will be disseminated to pediatric
      quality public health and mHealth communities through scientific meetings and
      through publications, nationally and internationally. CONCLUSIONS: This study
      will provide insight regarding efficacy of using mHealth-based reminder services
      for patient's appointments in low- and middle-income countries setup. The finding
      of this study will be used to recommend further enhanced mHealth-based solutions
      to improve patient appointments and decrease no show.

PMID- 29636320
TI  - A Behavioral Lifestyle Intervention Enhanced With Multiple-Behavior Self
      Monitoring Using Mobile and Connected Tools for Underserved Individuals With Type
      2 Diabetes and Comorbid Overweight or Obesity: Pilot Comparative Effectiveness
      Trial.
AB  - BACKGROUND: Self-monitoring is a cornerstone of behavioral lifestyle
      interventions for obesity and type 2 diabetes mellitus. Mobile technology has the
      potential to improve adherence to self-monitoring and patient outcomes. However,
      no study has tested the use of a smartphone to facilitate self-monitoring in
      overweight or obese adults with type 2 diabetes mellitus living in the
      underserved community. OBJECTIVE: The aim of this study was to examine the
      feasibility of and compare preliminary efficacy of a behavioral lifestyle
      intervention using smartphone- or paper-based self-monitoring of multiple
      behaviors on weight loss and glycemic control in a sample of overweight or obese
      adults with type 2 diabetes mellitus living in underserved communities. METHODS:
      We conducted a randomized controlled trial to examine the feasibility and
      preliminary efficacy of a behavioral lifestyle intervention. Overweight or obese
      patients with type 2 diabetes mellitus were recruited from an underserved
      minority community health center in Houston, Texas. They were randomly assigned
      to one of the three groups: (1) behavior intervention with smartphone-based self
      monitoring, (2) behavior intervention with paper diary-based self-monitoring, and
      (3) usual care group. Both the mobile and paper groups received a total of 11
      face-to-face group sessions in a 6-month intervention. The mobile group received
      an Android-based smartphone with 2 apps loaded to help them record their diet,
      physical activity, weight, and blood glucose, along with a connected glucometer,
      whereas the paper group used paper diaries for these recordings. Primary outcomes
      of the study included percentage weight loss and glycated hemoglobin (HbA1c)
      changes over 6 months. RESULTS: A total of 26 patients were enrolled: 11 in the
      mobile group, 9 in the paper group, and 6 in the control group. We had 92%
      (24/26) retention rate at 6 months. The sample is predominantly African Americans
      with an average age of 56.4 years and body mass index of 38.1. Participants lost
      an average of 2.73% (mobile group) and 0.13% (paper group) weight at 6 months,
      whereas the control group had an average 0.49% weight gain. Their HbA1c changed
      from 8% to 7 % in mobile group, 10% to 9% in paper group, and maintained at 9%
      for the control group. We found a significant difference on HbA1c at 6 months
      among the 3 groups (P=.01). We did not find statistical group significance on
      percentage weight loss (P=.20) and HbA1c changes (P=.44) overtime; however, we
      found a large effect size of 0.40 for weight loss and a medium effect size of
      0.28 for glycemic control. CONCLUSIONS: Delivering a simplified behavioral
      lifestyle intervention using mobile health-based self-monitoring in an
      underserved community is feasible and acceptable and shows higher preliminary
      efficacy, as compared with paper-based self-monitoring. A full-scale randomized
      controlled trial is needed to confirm the findings in this pilot study. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT02858648;
      https://clinicaltrials.gov/ct2/show/NCT02858648 (Archived by WebCite at
      http://www.webcitation.org/6ySidjmT7).

PMID- 29636322
TI  - Online Lectures in Undergraduate Medical Education: Scoping Review.
AB  - BACKGROUND: The adoption of the flipped classroom in undergraduate medical
      education calls on students to learn from various self-paced tools-including
      online lectures-before attending in-class sessions. Hence, the design of online
      lectures merits special attention, given that applying multimedia design
      principles has been shown to enhance learning outcomes. OBJECTIVE: The aim of
      this study was to understand how online lectures have been integrated into
      medical school curricula, and whether published literature employs well-accepted
      principles of multimedia design. METHODS: This scoping review followed the
      methodology outlined by Arksey and O'Malley (2005). Databases, including MEDLINE,
      PsycINFO, Education Source, FRANCIS, ERIC, and ProQuest, were searched to find
      articles from 2006 to 2016 related to online lecture use in undergraduate medical
      education. RESULTS: In total, 45 articles met our inclusion criteria. Online
      lectures were used in preclinical and clinical years, covering basic sciences,
      clinical medicine, and clinical skills. The use of multimedia design principles
      was seldom reported. Almost all studies described high student satisfaction and
      improvement on knowledge tests following online lecture use. CONCLUSIONS:
      Integration of online lectures into undergraduate medical education is well
      received by students and appears to improve learning outcomes. Future studies
      should apply established multimedia design principles to the development of
      online lectures to maximize their educational potential.

PMID- 29636324
TI  - UK will invest L75m in research to improve prostate cancer care.

PMID- 29636325
TI  - Nurse specialists could help patients and consultants prepare for appointments.

PMID- 29636323
TI  - Engagement With a Trauma Recovery Internet Intervention Explained With the Health
      Action Process Approach (HAPA): Longitudinal Study.
AB  - BACKGROUND: There has been a growing trend in the delivery of mental health
      treatment via technology (ie, electronic health, eHealth). However, engagement
      with eHealth interventions is a concern, and theoretically based research in this
      area is sparse. Factors that influence engagement are poorly understood,
      especially in trauma survivors with symptoms of posttraumatic stress. OBJECTIVE:
      The aim of this study was to examine engagement with a trauma recovery eHealth
      intervention using the Health Action Process Approach theoretical model. Outcome
      expectancy, perceived need, pretreatment self-efficacy, and trauma symptoms
      influence the formation of intentions (motivational phase), followed by planning,
      which mediates the translation of intentions into engagement (volitional phase).
      We hypothesized the mediational effect of planning would be moderated by level of
      treatment self-efficacy. METHODS: Trauma survivors from around the United States
      used the eHealth intervention for 2 weeks. We collected baseline demographic,
      social cognitive predictors, and distress symptoms and measured engagement
      subjectively and objectively throughout the intervention. RESULTS: The
      motivational phase model explained 48% of the variance, and outcome expectations
      (beta=.36), perceived need (beta=.32), pretreatment self-efficacy (beta=.13), and
      trauma symptoms (beta=.21) were significant predictors of intention (N=440). In
      the volitional phase, results of the moderated mediation model indicated for low
      levels of treatment self-efficacy, planning mediated the effects of intention on
      levels of engagement (B=0.89, 95% CI 0.143-2.605; N=115). CONCLUSIONS: Though
      many factors can affect engagement, these results offer a theoretical framework
      for understanding engagement with an eHealth intervention. This study highlighted
      the importance of perceived need, outcome expectations, self-efficacy, and
      baseline distress symptoms in the formation of intentions to use the
      intervention. For those low in treatment self-efficacy, planning may play an
      important role in the translation of intentions into engagement. Results of this
      study may help bring some clarification to the question of what makes eHealth
      interventions work.

PMID- 29636327
TI  - Should all patients with Hodgkin lymphoma who relapse after autologous SCT be
      considered for allogeneic SCT?

PMID- 29636326
TI  - Total metabolic tumor volume, circulating tumor cells, cell-free DNA: distinct
      prognostic value in follicular lymphoma.
AB  - Outcomes for follicular lymphoma (FL) have greatly improved, but most patients
      will ultimately relapse. High total metabolic tumor volume (TMTV), computed from
      baseline 18F-fluorodeoxyglucose-positron emission tomography (PET), is associated
      with shorter progression-free survival (PFS), but circulating tumor cells (CTCs)
      and cell-free DNA (cfDNA) may also reflect tumor burden and be of prognostic
      value. The aim of our study was to correlate CTCs and cfDNA with TMTV in FL at
      diagnosis and to determine their prognostic values. We retrospectively analyzed
      133 patients (with previously untreated FL and a baseline PET) from 2 cohorts
      with either a baseline plasma sample (n = 61) or a bcl2-JH-informative peripheral
      blood (PB) sample (n = 68). Quantification of circulating bcl2-JH+ cells and
      cfDNA was performed by droplet digital polymerase chain reaction. A significant
      correlation was found between TMTV and both CTCs (P < .0001) and cfDNA (P <
      .0001). With a median 48-month follow-up, 4-year PFS was lower in patients with
      TMTV > 510 cm3 (P = .0004), CTCs >0.0018 PB cells (P = .03), or cfDNA >2550
      equivalent-genome/mL (P = .04). In comparison with TMTV alone, no additional
      prognostic information was obtained by measuring CTCs. In contrast, Cox
      multivariate analysis, including cfDNA and TMTV, showed that both cfDNA and TMTV
      remained predictive of outcome. In conclusion, CTCs and cfDNA correlate with TMTV
      in FL, and all 3 influence patient outcome. PFS was shorter for patients with
      high cfDNA and TMTV, suggesting that these parameters provide relevant
      information for tumor-tailored therapy.

PMID- 29636329
TI  - Curriculum vitae: Rob Bentley.

PMID- 29636328
TI  - Should all patients with HL who relapse after ASCT be considered for allogeneic
      SCT? A consult, yes; a transplant, not necessarily.

PMID- 29636330
TI  - Selenoprotein P Promotes the Development of Pulmonary Arterial Hypertension.
AB  - BACKGROUND: Excessive proliferation and apoptosis resistance of pulmonary artery
      smooth muscle cells (PASMCs) are key mechanisms of pulmonary arterial
      hypertension (PAH). Despite the multiple combination therapy, a considerable
      number of patients develop severe pulmonary hypertension (PH) because of the lack
      of diagnostic biomarker and antiproliferative therapies for PASMCs. METHODS:
      Microarray analyses were used to identify a novel therapeutic target for PAH. In
      vitro experiments, including lung and serum samples from patients with PAH,
      cultured PAH-PASMCs, and high-throughput screening of 3336 low-molecular-weight
      compounds, were used for mechanistic study and exploring a novel therapeutic
      agent. Five genetically modified mouse strains, including PASMC-specific
      selenoprotein P (SeP) knockout mice and PH model rats, were used to study the
      role of SeP and therapeutic capacity of the compounds for the development of PH
      in vivo. RESULTS: Microarray analysis revealed a 32-fold increase in SeP in PAH
      PASMCs compared with control PASMCs. SeP is a widely expressed extracellular
      protein maintaining cellular metabolism. Immunoreactivity of SeP was enhanced in
      the thickened media of pulmonary arteries in PAH. Serum SeP levels were also
      elevated in patients with PH compared with controls, and high serum SeP predicted
      poor outcome. SeP-knockout mice ( SeP-/-) exposed to chronic hypoxia showed
      significantly reduced right ventricular systolic pressure, right ventricular
      hypertrophy, and pulmonary artery remodeling compared with controls. In contrast,
      systemic SeP-overexpressing mice showed exacerbation of hypoxia-induced PH.
      Furthermore, PASMC-specific SeP-/- mice showed reduced hypoxia-induced PH
      compared with controls, whereas neither liver-specific SeP knockout nor liver
      specific SeP-overexpressing mice showed significant differences with controls.
      Altogether, protein levels of SeP in the lungs were associated with the
      development of PH. Mechanistic experiments demonstrated that SeP promotes PASMC
      proliferation and resistance to apoptosis through increased oxidative stress and
      mitochondrial dysfunction, which were associated with activated hypoxia-inducible
      factor-1alpha and dysregulated glutathione metabolism. It is important to note
      that the high-throughput screening of 3336 compounds identified that
      sanguinarine, a plant alkaloid with antiproliferative effects, reduced SeP
      expression and proliferation in PASMCs and ameliorated PH in mice and rats.
      CONCLUSIONS: These results indicate that SeP promotes the development of PH,
      suggesting that it is a novel biomarker and therapeutic target of the disorder.

PMID- 29636332
TI  - Intradermal pre-exposure rabies vaccination in a Canadian travel clinic: 6-year
      retrospective observational study.
AB  - BACKGROUND: The intradermal route of vaccine administration for pre-exposure
      rabies prophylaxis, endorsed by the Canadian National Advisory Committee on
      Immunization, was implemented at a large travel clinic in Montreal in 2008. We
      evaluated the effect of intradermal vaccination availability on uptake of pre
      exposure rabies prophylaxis and rates of seroconversion with intradermal
      vaccination. METHODS: We conducted a retrospective cross-sectional study using
      data from December 2008 to December 2014. The number of travellers who received
      pre-exposure rabies prophylaxis before and after the introduction of intradermal
      vaccination was compared. Postvaccination antibody titres were measured in
      intradermal vaccination recipients. We compared demographic and travel
      characteristics between vaccinated and unvaccinated travellers and between
      travellers in the intradermal and intramuscular groups using univariate and
      multivariate analyses. RESULTS: The proportion of travellers who received pre
      exposure prophylaxis increased after the introduction of intradermal vaccination
      (annual average of 300 travellers from December 2009 to December 2014 v. 183
      travellers from December 2006 to December 2007). Seroconversion occurred in 99.9%
      of those in the intradermal group. Travellers who received pre-exposure
      prophylaxis were older (mean age 35.8 yr v. 32.1 yr) and had longer travel
      duration than those who did not receive pre-exposure prophylaxis. Travellers to
      Asia were more likely to receive pre-exposure prophylaxis, and travellers
      visiting friends and relatives were less likely to receive it. Travellers in the
      intradermal group were younger than those in the intramuscular group and were
      more likely to be travelling for tourism. INTERPRETATION: The introduction of
      intradermal vaccination for pre-exposure rabies prophylaxis was associated with
      an increase in vaccination uptake. Reduced cost may be responsible for the
      increased coverage among younger travellers and those travelling for tourism. The
      high seroconversion rate after intradermal vaccination supports the effectiveness
      of this route of administration for pre-exposure rabies prophylaxis in
      immunocompetent people.

PMID- 29636334
TI  - The rise of ambiguous competing interest declarations.

PMID- 29636335
TI  - Blind spot: blindness as initial presentation of subarachnoid haemorrhage.
AB  - A 47-year-old Caucasian man with arterial hypertension was admitted after a
      seizure. At the emergency department, he presented with high blood pressure,
      bilateral vision loss (evidenced by unresponsiveness to threatening stimuli),
      right hemiplegia and severe agitation. The brain CT angiography showed a diffuse
      basal cisterns subarachnoid haemorrhage with a ruptured basilar aneurysm. He was
      admitted for neurovascular procedure and embolisation. The patient's neurological
      examination improved but blindness persisted. A funduscopic examination revealed
      a left eye vitreous haemorrhage and diffuse retinal haemorrhages in the posterior
      pole. Assuming the haemorrhages were the cause of blindness, Terson syndrome was
      diagnosed. The patient underwent vitrectomy surgery being discharged 5 days later
      maintaining left eye blindness and able to count fingers from 1 m distance with
      the right eye. Two months after discharge, he was re-evaluated at our clinic with
      left eye blurred vision and almost normal right eye visual acuity.

PMID- 29636336
TI  - Ichthyosis: A Harbinger of Lymphoma.

PMID- 29636337
TI  - Bland-White-Garland syndrome on coronary CT angiography.

PMID- 29636338
TI  - Rocuronium for control of muscle spasms in a tetanus patient with chronic
      methamphetamine use disorder.
AB  - This is a case of a 31-year-old Filipino man with chronic methamphetamine use
      disorder who developed tetanus from a necrotic skin graft over his left
      calcaneus, which was fractured after a motor vehicular accident. During the
      course of his illness, the patient's muscle spasms were unusually refractory to
      benzodiazepine, which is the first-line drug used in the management of muscle
      spasms. The muscle spasms were successfully controlled on the seventh day of
      illness with rocuronium at a dose of 10 MUg/kg/min and midazolam at 0.30
      mg/kg/hour. Both infusions were tapered off until the 23rd day of illness. The
      patient was discharged on the 30th day of illness, improved and stable.

PMID- 29636340
TI  - A common misconception about hand positioning in scans.

PMID- 29636339
TI  - Wellens' syndrome: a pattern to remember.

PMID- 29636341
TI  - Fat Intake and Risk of Skin Cancer in U.S. Adults.
AB  - Background: Fat intake has been associated with certain cancers, including
      colorectal, breast, and prostate cancers. However, literature on dietary fat and
      skin cancer has been limited.Methods: We examined the association between fat
      intake and risk of skin cancer including cutaneous malignant melanoma, squamous
      cell carcinoma (SCC), and basal cell carcinoma (BCC) within two prospective
      studies: the Nurses' Health Study (NHS) and the Health Professionals Follow-up
      Study (HPFS). Dietary information on total, saturated, monounsaturated,
      polyunsaturated, omega-6, and omega-3 fat and cholesterol was repeatedly assessed
      generally every 4 years. Incident cases were identified by self-report. Diagnosis
      on melanoma and SCC was confirmed by pathologic records.Results: A total of 794
      melanoma, 2,223 SCC, and 17,556 BCC in the NHS (1984-2012) and 736 melanoma,
      1,756 SCC, and 13,092 BCC in the HPFS (1986-2012) were documented. Higher
      polyunsaturated fat intake was associated with risk of SCC [pooled HR for highest
      vs. lowest quintiles, 1.16; 95% confidence interval (CI), 1.05-1.28;
      Ptrend=0.001] and BCC (pooled HR, 1.06; 95% CI, 1.01-1.11; Ptrend=0.01). Higher
      omega-6 fat intake was associated with risks of SCC, BCC, and melanoma. Omega-3
      fat intake was associated with risk of BCC, but not with SCC or melanoma. No
      other fats were associated with melanoma risk. The associations were similar in
      women and men and by other skin cancer risk factors.Conclusions: Polyunsaturated
      fat intake was modestly associated with skin cancer risk.Impact: Further studies
      are needed to confirm our findings and to identify relevant biological
      mechanisms. Cancer Epidemiol Biomarkers Prev; 27(7); 776-82. (c)2018 AACR.

PMID- 29636343
TI  - Clarifying the roles of patients in research.

PMID- 29636342
TI  - Circadian Misalignment and Hepatocellular Carcinoma Incidence in the United
      States.
AB  - Background: Circadian misalignment may increase the risk of developing
      hepatocellular carcinoma (HCC). The aim of this study was to examine the
      association between distance from time zone meridian, a proxy for circadian
      misalignment, and HCC risk in the United States adjusting for known HCC risk
      factors.Methods: Surveillance, Epidemiology, and End Results (SEER) provided
      information on 56,347 HCC cases diagnosed between 2000 and 2014 from 16
      population-based cancer registries in the United States. Distance from time zone
      meridian was estimated using the location of each SEER county's Center of
      Population in a geographic information system. Poisson regression with robust
      variance estimation was used to calculate incidence rate ratios (IRRs) and 95%
      confidence intervals (CIs) for the association between distance from time zone
      meridian and HCC risk adjusting for individual-level age at diagnosis, sex,
      race/ethnicity, year of diagnosis, SEER registry, and county-level prevalence of
      health conditions, lifestyle factors, shift work occupation, socioeconomic
      status, and demographic and environmental factors.Results: A 5-degree increase in
      longitude moving east to west within a time zone was associated with a
      statistically significant increased risk for HCC (IRR, 1.07; 95% CI, 1.01-1.14, P
      = 0.03). A statistically significant positive association was observed among
      those <65 years old, while no association was observed among individuals >=65
      years old (Pfor interaction < 0.01).Conclusions: Circadian misalignment from
      residing in the western region of a time zone may impact
      hepatocarcinogenesis.Impact: Circadian misalignment may be an independent risk
      factor for HCC. Cancer Epidemiol Biomarkers Prev; 27(7); 719-27. (c)2018 AACR.

PMID- 29636344
TI  - David Oliver: Will the public use alternatives to emergency departments?

PMID- 29636345
TI  - Enhanced Lymphodepletion Is Insufficient to Replace Exogenous IL2 or IL15 Therapy
      in Augmenting the Efficacy of Adoptively Transferred Effector CD8+ T Cells.
AB  - Effector CD8+ T cells conditioned with IL12 during activation mediate enhanced
      antitumor efficacy after adoptive transfer into lymphodepleted hosts; this is due
      in part to improved IL7 responsiveness. Therefore, we hypothesized that
      increasing the intensity or type of lymphodepletion would deplete more IL7
      consuming host cells and improve the persistence and antitumor activity of IL12
      conditioned CD8+ T cells. Using cyclophosphamide, fludarabine, and total body
      irradiation (TBI, 6 Gy) either individually or in combination, we found that
      combined lymphodepletion best enhanced T-cell engraftment in mice. This
      improvement was strongly related to the extent of leukopenia, as posttransfer
      levels of donor T cells inversely correlated to host cell counts after
      lymphodepletion. Despite the improvement in engraftment seen with combination
      lymphodepletion, dual-agent lymphodepletion did not augment the antitumor
      efficacy of donor T cells compared with TBI alone. Similarly, IL7 supplementation
      after TBI and transfer of tumor-reactive T cells failed to improve persistence or
      antitumor immunity. However, IL15 or IL2 supplementation greatly augmented the
      persistence and antitumor efficacy of donor tumor-reactive T cells. Our results
      indicate that the amount of host IL7 induced after single agent lymphodepletion
      is sufficient to potentiate the expansion and antitumor activity of donor T
      cells, and that the efficacy of future regimens may be improved by providing
      posttransfer support with IL2 or IL15.Significance: The relationship between
      lymphodepletion and cytokine support plays a critical role in determining donor T
      cell engraftment and antitumor efficacy. Cancer Res; 78(11); 3067-74. (c)2018
      AACR.

PMID- 29636347
TI  - Letter by Hochman and Maron Regarding Article, "'Faith Healing' and 'Subtraction
      Anxiety' in Unblinded Trials of Procedures: Lessons From DEFER and FAME-2 for End
      Points in the ISCHEMIA Trial."

PMID- 29636346
TI  - Association of "Elevated Blood Pressure" and "Stage 1 Hypertension" With
      Cardiovascular Mortality Among an Asian Population.
AB  - BACKGROUND: The new American College of Cardiology/American Heart Association
      high blood pressure (BP) guidelines in the United States have lowered definition
      of hypertension by defining normal as systolic/diastolic BP <120/80 mm Hg;
      elevated BP as systolic between 120 and 129 mm Hg and diastolic <80 mm Hg; and
      stage 1 hypertension as systolic between 130 and 139 mm Hg or diastolic between
      80 and 89 mm Hg. METHODS AND RESULTS: We investigated the association between the
      new hypertension definition and cardiovascular disease mortality among Chinese in
      Singapore. We used data from 30 636 participants of a population-based cohort,
      the SCHS (Singapore Chinese Health Study), who had BPs measured using a standard
      protocol at ages 46 to 85 years between 1994 and 2005. Information on lifestyle
      factors was collected at recruitment (1993-1998) and follow-up 1 interviews (1999
      and 2004). Mortality was identified via nationwide registry linkage up to
      December 31, 2016. Neither elevated BP (hazard ratio, 0.89; 95% confidence
      interval, 0.74-1.07) nor stage 1 hypertension (hazard ratio, 0.94; 95% confidence
      interval, 0.81-1.11) was associated with increased risk of cardiovascular
      mortality compared with normal BP in the whole cohort. Stage 1 hypertension was
      associated with increased cardiovascular risk only in those <65 years of age and
      without a history of cardiovascular disease (hazard ratio, 1.40; 95% confidence
      interval, 1.01-1.94), but not in those >=65 years of age or with a history of
      cardiovascular disease. CONCLUSIONS: Our data suggest that the newly defined
      stage 1 hypertension may not be associated with increased cardiovascular
      mortality across all ages among Chinese in Singapore, but that the at-risk
      subpopulation is limited to those <65 years of age and without a prior
      cardiovascular disease.

PMID- 29636348
TI  - Margaret McCartney: Trust has to be earned.

PMID- 29636349
TI  - Bawa-Garba case fallout: five minutes with . . . David Galloway.

PMID- 29636350
TI  - Calcium-Induced Differentiation of Human Colon Adenomas in Colonoid Culture:
      Calcium Alone versus Calcium with Additional Trace Elements.
AB  - Previous murine studies have demonstrated that dietary Aquamin, a calcium-rich,
      multi-mineral natural product, suppressed colon polyp formation and transition to
      invasive tumors more effectively than calcium alone when provided over the
      lifespan of the animals. In the current study, we compared calcium alone to
      Aquamin for modulation of growth and differentiation in human colon adenomas in
      colonoid culture. Colonoids established from normal colonic tissue were examined
      in parallel. Both calcium alone at 1.5 mmol/L and Aquamin (provided at 1.5 mmol/L
      calcium) fostered differentiation in the adenoma colonoid cultures as compared
      with control (calcium at 0.15 mmol/L). When Aquamin was provided at an amount
      delivering 0.15 mmol/L calcium, adenoma differentiation also occurred, but was
      not as complete. Characteristic of colonoids undergoing differentiation was a
      reduction in the number of small, highly proliferative buds and their replacement
      by fewer but larger buds with smoother surface. Proliferation marker (Ki67)
      expression was reduced and markers of differentiation (CK20 and occludin) were
      increased along with E-cadherin translocalization to the cell surface. Additional
      proteins associated with differentiation/growth control [including histone-1
      family members, certain keratins, NF2 (merlin), olfactomedin-4 and
      metallothioneins] were altered as assessed by proteomics. Immunohistologic
      expression of NF2 was higher with Aquamin as compared with calcium at either
      concentration. These findings support the conclusions that (i) calcium (1.5
      mmol/L) has the capacity to modulate growth and differentiation in large human
      colon adenomas and (ii) Aquamin delivering 0.15 mmol/L calcium has effects on
      proliferation and differentiation not observed when calcium is used alone at this
      concentration. Cancer Prev Res; 11(7); 413-28. (c)2018 AACR.

PMID- 29636351
TI  - Ultraviolet Radiation Inhibits Mammary Carcinogenesis in an ER-Negative Murine
      Model by a Mechanism Independent of Vitamin D3.
AB  - Three decades ago, the Garlands postulated that vitamin D3 produced in the skin
      by ultraviolet radiation (UVR)-induced conversion of 7-dehydrocholesterol to pre
      D3 has anticancer effects, thus triggering more than 9,500 publications on D3 and
      cancer. Here, we report that UVR treatment of transgenic mice of the well
      established C3(1)/SV40 Tag mammary cancer model significantly inhibits both
      autochthonous carcinogenesis and allograft tumor growth, but in contrast neither
      dietary nor topical D3 influences mammary carcinogenesis in this specific mouse
      model. Furthermore, UVR's inhibitory effects occur irrespective of whether or not
      the treatment increases circulating D3 in the mice. The inhibitory effect of UVR
      on autochthonous tumors occurs at or before the stage of ductal carcinoma in
      situ. Our studies indicate clearly that UVR can exert D3-independent anticancer
      effects in C3(1)/SV40 Tag mice. Therefore, supplemental D3 may not mimic all
      possible beneficial effects of UVR, and uncovering non-D3-mediated mechanisms of
      UVR tumor inhibition may lead to novel strategies for cancer prevention. Cancer
      Prev Res; 11(7); 383-92. (c)2018 AACR.

PMID- 29636352
TI  - Spatial Variation of the Native Colon Microbiota in Healthy Adults.
AB  - The microbiome has been implicated in the development of colorectal cancer and
      inflammatory bowel diseases. The specific traits of these diseases vary along the
      axis of the digestive tract. Further, variation in the structure of the gut
      microbiota has been associated with both diseases. We profiled the microbiota of
      the healthy proximal and distal mucosa and lumen to better understand how
      bacterial populations vary along the colon. We used a two-colonoscope approach to
      sample proximal and distal mucosal and luminal contents from the colons of 20
      healthy subjects that had not undergone any bowel preparation procedure. The
      biopsies and home-collected stool were subjected to 16S rRNA gene sequencing, and
      random forest classification models were built using taxa abundance and location
      to identify microbiota specific to each site. The right mucosa and lumen had the
      most similar community structures of the five sites we considered from each
      subject. The distal mucosa had higher relative abundance of Finegoldia,
      Murdochiella, Peptoniphilus, Porphyromonas, and Anaerococcus The proximal mucosa
      had more of the genera Enterobacteriaceae, Bacteroides, and Pseudomonas The
      classification model performed well when classifying mucosal samples into
      proximal or distal sides (AUC = 0.808). Separating proximal and distal luminal
      samples proved more challenging (AUC = 0.599), and specific microbiota that
      differentiated the two were hard to identify. By sampling the unprepped colon, we
      identified distinct bacterial populations native to the proximal and distal
      sides. Further investigation of these bacteria may elucidate if and how these
      groups contribute to different disease processes on their respective sides of the
      colon. Cancer Prev Res; 11(7); 393-402. (c)2018 AACR.

PMID- 29636353
TI  - Appetite, Glycemia, and Entero-Insular Hormone Responses Differ Between Oral,
      Gastric-Remnant, and Duodenal Administration of a Mixed-Meal Test After Roux-en-Y
      Gastric Bypass.
AB  - OBJECTIVE: To examine the effect of different feeding routes on appetite and
      metabolic responses after Roux-en-Y gastric bypass (RYGB). RESEARCH DESIGN AND
      METHODS: A standard liquid meal was administered either orally, into the gastric
      remnant, or intraduodenally 6 months after RYGB. Changes in plasma glucose,
      insulin, glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic
      peptide (GIP), peptide YY (PYY), and appetite were measured pre- and
      postprandially. RESULTS: Postprandial GLP-1 and PYY responses were similar,
      whereas glucose, insulin, and GIP levels differed markedly after oral versus
      intraduodenal feeding. Intraduodenal feeding prompted an intermediate appetite
      response (i.e., between oral and intragastric). For postprandial glucose,
      insulin, and GIP levels, the intraduodenal route was more similar to the
      intragastric than the oral route. Intragastric administration did not evoke
      changes in appetite, glucose, or insulin; however, it slightly increased GLP-1
      and PYY and moderately increased GIP. CONCLUSIONS: Appetite and metabolic
      responses after RYGB depend on the route by which nutrients enter the
      gastrointestinal tract.

PMID- 29636354
TI  - Prevalence and treatment of panic disorder in bipolar disorder: systematic review
      and meta-analysis.
AB  - QUESTION: Recent data suggest that anxiety disorders are as often comorbid with
      bipolar disorder (BD) as with unipolar depression. The literature on panic
      disorder (PD) comorbid with BD has been systematically reviewed and subject to
      meta-analysis. STUDY SELECTION AND ANALYSIS: The Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses guidelines were thoroughly followed for
      literature search, selection and reporting of available evidence. The variance
      stabilising Freeman-Tukey double arcsine transformation was used in the meta
      analysis of prevalence estimates. Both fixed-effect and random-effects models
      with inverse variance method were applied to estimate summary effects for all
      combined studies. Heterogeneity was assessed and measured with Cochran's Q and I2
      statistics. FINDINGS: Overall, 15 studies (n=3391) on cross-sectional prevalence
      and 25 independent lifetime studies (n=8226) were used to calculate pooled
      estimates. The overall random-effects point prevalence of PD in patients with BD,
      after exclusion of one potential outlier study, was 13.0% (95% CI 7.0% to 20.3%),
      and the overall random-effects lifetime estimate, after exclusion of one
      potential outlier study, was 15.5% (95% CI 11.6% to 19.9%). There were no
      differences in rates between BD-I and BD-II. Significant heterogeneity (I2 >95%)
      was found in both estimates. CONCLUSIONS: Estimates that can be drawn from
      published studies indicate that the prevalence of PD in patients with BD is
      higher than the prevalence in the general population. Comorbid PD is reportedly
      associated with increased risk of suicidal acts and a more severe course. There
      is no clear indication on how to treat comorbid PD in BD. Findings from the
      current meta-analysis confirm the highly prevalent comorbidity of PD with BD,
      implicating that in patients with BD, PD might run a more chronic course.

PMID- 29636356
TI  - Primary aldosteronism: key characteristics at diagnosis: a trend toward milder
      forms.
AB  - OBJECTIVE: Primary aldosteronism (PA) is the most common endocrine form of
      arterial hypertension. The German Conn's Registry's purpose is to improve
      treatment outcomes of PA. We assessed whether key clinical, biochemical and
      epidemiological characteristics of newly diagnosed PA cases have changed over
      time, potentially indicating a different screening and referral practice in
      Germany evolving from 2008 to 2016. DESIGN: The German Conn's Registry is a
      multicenter database prospectively analyzing morbidity and long-term outcome of
      patients with PA. METHODS: Phenotypic changes between three year periods were
      calculated using Mann-Whitney U tests and Kruskal-Wallis tests for independent
      variables. RESULTS: Over three time periods from 2008 to 2016, we noted a
      relative decrease of unilateral PA cases (67 vs 43%). Significantly more females
      were diagnosed with PA (33 vs 43%). Median daily defined drug doses decreased
      (3.1 vs 2.0) in the presence of unchanged SBP (150 vs 150 mmHg), plasma
      aldosterone (199 vs 173 ng/L) and PRC (3.2 vs 3.2 U/L). Median ARR values
      decreased (70 vs 47 ng/U) and median potassium levels at diagnosis (3.5 vs 3.7
      mmol/L) increased as the percentage of normokalemic patients (25 vs 41%),
      indicating milder forms of PA. CONCLUSIONS: Our results are in accordance with an
      increased screening intensity for PA. We identified a trend toward diagnosing
      milder forms, increasingly more females and less unilateral cases of PA.

PMID- 29636355
TI  - Family Consultation to Reduce Early Hospital Readmissions among Patients with End
      Stage Kidney Disease: A Randomized Controlled Trial.
AB  - BACKGROUND AND OBJECTIVES: The US Centers for Medicare and Medicaid Services have
      mandated reducing early (30-day) hospital readmissions to improve patient care
      and reduce costs. Patients with ESKD have elevated early readmission rates, due
      in part to complex medical regimens but also cognitive impairment, literacy
      difficulties, low social support, and mood problems. We developed a brief family
      consultation intervention to address these risk factors and tested whether it
      would reduce early readmissions. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:
      One hundred twenty hospitalized adults with ESKD (mean age=58 years; 50% men; 86%
      black, 14% white) were recruited from an urban, inpatient nephrology unit.
      Patients were randomized to the family consultation (n=60) or treatment-as-usual
      control (n=60) condition. Family consultations, conducted before discharge at
      bedside or via telephone, educated the family about the patient's cognitive and
      behavioral risk factors for readmission, particularly cognitive impairment, and
      how to compensate for them. Blinded medical record reviews were conducted 30 days
      later to determine readmission status (primary outcome) and any hospital return
      visit (readmission, emergency department, or observation; secondary outcome).
      Logistic regressions tested the effects of the consultation versus control on
      these outcomes. RESULTS: Primary analyses were intent-to-treat. The risk of a 30
      day readmission after family consultation (n=12, 20%) was 0.54 compared with
      treatment-as-usual controls (n=19, 32%), although this effect was not
      statistically significant (odds ratio, 0.54; 95% confidence interval, 0.23 to
      1.24; P=0.15). A similar magnitude, nonsignificant result was observed for any 30
      day hospital return visit: family consultation (n=19, 32%) versus controls (n=28,
      47%; odds ratio, 0.53; 95% confidence interval, 0.25 to 1.1; P=0.09). Per
      protocol analyses (excluding three patients who did not receive the assigned
      consultation) revealed similar results. CONCLUSIONS: A brief consultation with
      family members about the patient's cognitive and psychosocial risk factors had no
      significant effect on 30-day hospital readmission in patients with ESKD.

PMID- 29636357
TI  - Discovery of a Glucocorticoid Receptor (GR) Activity Signature Using Selective GR
      Antagonism in ER-Negative Breast Cancer.
AB  - Purpose: Although high glucocorticoid receptor (GR) expression in early-stage
      estrogen receptor (ER)-negative breast cancer is associated with shortened
      relapse-free survival (RFS), how associated GR transcriptional activity
      contributes to aggressive breast cancer behavior is not well understood. Using
      potent GR antagonists and primary tumor gene expression data, we sought to
      identify a tumor-relevant gene signature based on GR activity that would be more
      predictive than GR expression alone.Experimental Design: Global gene expression
      and GR ChIP-sequencing were performed to identify GR-regulated genes inhibited by
      two chemically distinct GR antagonists, mifepristone and CORT108297.
      Differentially expressed genes from MDA-MB-231 cells were cross-evaluated with
      significantly expressed genes in GR-high versus GR-low ER-negative primary breast
      cancers. The resulting subset of GR-targeted genes was analyzed in two
      independent ER-negative breast cancer cohorts to derive and then validate the GR
      activity signature (GRsig).Results: Gene expression pathway analysis of
      glucocorticoid-regulated genes (inhibited by GR antagonism) revealed cell
      survival and invasion functions. GR ChIP-seq analysis demonstrated that GR
      antagonists decreased GR chromatin association for a subset of genes. A GRsig
      that comprised n = 74 GR activation-associated genes (also reversed by GR
      antagonists) was derived from an adjuvant chemotherapy-treated Discovery cohort
      and found to predict probability of relapse in a separate Validation cohort (HR =
      1.9; P = 0.012).Conclusions: The GRsig discovered herein identifies high-risk ER
      negative/GR-positive breast cancers most likely to relapse despite administration
      of adjuvant chemotherapy. Because GR antagonism can reverse expression of these
      genes, we propose that addition of a GR antagonist to chemotherapy may improve
      outcome for these high-risk patients. Clin Cancer Res; 24(14); 3433-46. (c)2018
      AACR.

PMID- 29636359
TI  - Targeting NAD+/PARP DNA Repair Pathway as a Novel Therapeutic Approach to SDHB
      Mutated Cluster I Pheochromocytoma and Paraganglioma.
AB  - Purpose: Cluster I pheochromocytomas and paragangliomas (PCPGs) tend to develop
      malignant transformation, tumor recurrence, and multiplicity. Transcriptomic
      profiling suggests that cluster I PCPGs and other related tumors exhibit
      distinctive changes in the tricarboxylic acid (TCA) cycle, the hypoxia signaling
      pathway, mitochondrial electron transport chain, and methylation status,
      suggesting that therapeutic regimen might be optimized by targeting these
      signature molecular pathways.Experimental Design: In the present study, we
      investigated the molecular signatures in clinical specimens from cluster I PCPGs
      in comparison with cluster II PCPGs that are related to kinase signaling and
      often present as benign tumors.Results: We found that cluster I PCPGs develop a
      dependency to mitochondrial complex I, evidenced by the upregulation of complex I
      components and enhanced NADH dehydrogenation. Alteration in mitochondrial
      function resulted in strengthened NAD+ metabolism, here considered as a key
      mechanism of chemoresistance, particularly, of succinate dehydrogenase subunit B
      (SDHB)-mutated cluster I PCPGs via the PARP1/BER DNA repair pathway. Combining a
      PARP inhibitor with temozolomide, a conventional chemotherapeutic agent, not only
      improved cytotoxicity but also reduced metastatic lesions, with prolonged overall
      survival of mice with SDHB knockdown PCPG allograft.Conclusions: In summary, our
      findings provide novel insights into an effective strategy for targeting cluster
      I PCPGs, especially those with SDHB mutations. Clin Cancer Res; 24(14); 3423-32.
      (c)2018 AACR.

PMID- 29636360
TI  - A First-in-Human Phase 1 Study of LY3023414, an Oral PI3K/mTOR Dual Inhibitor, in
      Patients with Advanced Cancer.
AB  - Purpose: The PI3K/mTOR pathway is frequently aberrated in cancer. LY3023414 is a
      potent and selective ATP-competitive inhibitor of class I PI3K isoforms, mTOR,
      and DNA-PK. Here we report the dose-escalation results of the first-in-human
      phase I study of LY3023414.Patients and Methods: A 3+3 dose escalation for once
      daily and twice-daily oral dosing of LY3023414 was followed by an expansion
      cohort for CYP3A4 drug-drug interaction (DDI) assessment. The primary objective
      was to determine the recommended phase 2 dose (RP2D). Additional objectives
      included safety, pharmacokinetics/pharmacodynamics, and antitumor
      activity.Results: Forty-seven patients with solid tumors received LY3023414 at
      once-daily (20-450 mg) or twice-daily dosing (150-250 mg). Dose-limiting
      toxicities were observed at 450 mg once-daily (thrombocytopenia, hypotension,
      hyperkalemia) in three of three patients, 250-mg twice-daily dosing
      (hypophosphatemia, fatigue, mucositis) in three of four patients, and in one of
      15 patients at 200 mg twice-daily (nausea). Common related AEs included nausea
      (38%), fatigue (34%), and vomiting (32%) and were mostly mild or moderate.
      LY3023414 pharmacokinetics demonstrated dose-dependent increase in exposure with
      >= 90% target inhibition at doses >=150 mg. DDI analysis demonstrated LY3023414
      to be a weak inhibitor of CYP3A4. Durable partial response was observed in a
      patient with endometrial cancer harboring PIK3R1 and PTEN truncating mutations,
      and 13 additional patients (28%) had a decrease in their target lesions by up to
      30%.Conclusions: LY3023414 has a tolerable safety profile and single-agent
      activity in patients with advanced cancers. The RP2D of LY3023414 monotherapy is
      200 mg twice daily based on safety, tolerability, and
      pharmacokinetic/pharmacodynamic data. Clin Cancer Res; 24(14); 3253-62. (c)2018
      AACR.

PMID- 29636361
TI  - PDGF-A signaling is required for secondary alveolar septation and controls
      epithelial proliferation in the developing lung.
AB  - Platelet-derived growth factor A (PDGF-A) signaling through PDGF receptor alpha
      is essential for alveogenesis. Previous studies have shown that Pdgfa-/- mouse
      lungs have enlarged alveolar airspace with absence of secondary septation, both
      distinctive features of bronchopulmonary dysplasia. To study how PDGF-A signaling
      is involved in alveogenesis, we generated lung-specific Pdgfa knockout mice
      (Pdgfafl/-; Spc-cre) and characterized their phenotype postnatally. Histological
      differences between mutant mice and littermate controls were visible after the
      onset of alveogenesis and maintained until adulthood. Additionally, we generated
      Pdgfafl/-; Spc-cre; PdgfraGFP/+ mice in which Pdgfra+ cells exhibit nuclear GFP
      expression. In the absence of PDGF-A, the number of PdgfraGFP+ cells was
      significantly decreased. In addition, proliferation of PdgfraGFP+ cells was
      reduced. During alveogenesis, PdgfraGFP+ myofibroblasts failed to form the alpha
      smooth muscle actin rings necessary for alveolar secondary septation. These
      results indicate that PDGF-A signaling is involved in myofibroblast proliferation
      and migration. In addition, we show an increase in both the number and
      proliferation of alveolar type II cells in Pdgfafl/-; Spc-cre lungs, suggesting
      that the increased alveolar airspace is not caused solely by deficient
      myofibroblast function.

PMID- 29636358
TI  - Resistance Mechanisms to Targeted Therapies in ROS1+ and ALK+ Non-small Cell Lung
      Cancer.
AB  - Purpose: Despite initial benefit from tyrosine kinase inhibitors (TKIs), patients
      with advanced non-small cell lung cancer (NSCLC) harboring ALK (ALK+) and ROS1
      (ROS1+) gene fusions ultimately progress. Here, we report on the potential
      resistance mechanisms in a series of patients with ALK+ and ROS1+ NSCLC
      progressing on different types and/or lines of ROS1/ALK-targeted
      therapy.Experimental Design: We used a combination of next-generation sequencing
      (NGS), multiplex mutation assay, direct DNA sequencing, RT-PCR, and FISH to
      identify fusion variants/partners and copy-number gain (CNG), kinase domain
      mutations (KDM), and copy-number variations (CNVs) in other cancer-related genes.
      We performed testing on 12 ROS1+ and 43 ALK+ patients.Results: One of 12 ROS1+
      (8%) and 15 of 43 (35%) ALK + patients harbored KDM. In the ROS1+ cohort, we
      identified KIT and beta-catenin mutations and HER2-mediated bypass signaling as
      non-ROS1-dominant resistance mechanisms. In the ALK+ cohort, we identified a
      novel NRG1 gene fusion, a RET fusion, 2 EGFR, and 3 KRAS mutations, as well as
      mutations in IDH1, RIT1, NOTCH, and NF1 In addition, we identified CNV in
      multiple proto-oncogenes genes including PDGFRA, KIT, KDR, GNAS, K/HRAS, RET,
      NTRK1, MAP2K1, and others.Conclusions: We identified a putative TKI resistance
      mechanism in six of 12 (50%) ROS1 + patients and 37 of 43 (86%) ALK+ patients.
      Our data suggest that a focus on KDMs will miss most resistance mechanisms;
      broader gene testing strategies and functional validation is warranted to devise
      new therapeutic strategies for drug resistance. Clin Cancer Res; 24(14); 3334-47.
      (c)2018 AACR.

PMID- 29636362
TI  - Exosomes Induce Fibroblast Differentiation into Cancer-Associated Fibroblasts
      through TGFbeta Signaling.
AB  - A particularly important tumor microenvironment relationship exists between
      cancer cells and surrounding stromal cells. Fibroblasts, in response to cancer
      cells, become activated and exhibit myofibroblastic characteristics that favor
      invasive growth and metastasis. However, the mechanism by which cancer cells
      promote activation of healthy fibroblasts into cancer-associated fibroblasts
      (CAF) is still not well understood. Exosomes are nanometer-sized vesicles that
      shuttle proteins and nucleic acids between cells to establish intercellular
      communication. Here, bladder cancer-derived exosomes were investigated to
      determine their role in the activation of healthy primary vesical fibroblasts.
      Exosomes released by bladder cancer cells are internalized by fibroblasts and
      promoted the proliferation and expression of CAF markers. In addition, cancer
      cell-derived exosomes contain TGFbeta and in exosome-induced CAFs SMAD-dependent
      signaling is activated. Furthermore, TGFbeta inhibitors attenuated CAF marker
      expression in healthy fibroblasts. Therefore, these data demonstrate that bladder
      cancer cells trigger the differentiation of fibroblasts to CAFs by exosomes
      mediated TGFbeta transfer and SMAD pathway activation. Finally, exosomal TGFbeta
      localized inside the vesicle and contributes 53.4% to 86.3% of the total TGFbeta
      present in the cancer cell supernatant. This study highlights a new function for
      bladder cancer exosomes as novel modulators of stromal cell
      differentiation.Implication: This study identifies exosomal TGFbeta as new
      molecular mechanism involved in cancer-associated fibroblast activation. Mol
      Cancer Res; 16(7); 1196-204. (c)2018 AACR.

PMID- 29636363
TI  - Estrogen receptor subtypes dictate the proliferative nature of the mammary gland.
AB  - Estrogen induces proliferation of breast epithelial cells and is responsible for
      breast development at puberty. This tightly regulated control is lost in estrogen
      receptor-positive (ER+) breast cancers, which comprise over 70% of all breast
      cancers. Currently, breast cancer diagnosis and treatment considers only the
      alpha isoform of ER; however, there is a second ER, ERbeta. Whilst ERalpha
      mediates estrogen-driven proliferation of the normal breast in puberty and breast
      cancers, ERbeta has been shown to exert an anti-proliferative effect on the
      normal breast. It is not known how the expression of each ER (alone or in
      combination) correlates with the ability of estrogen to induce proliferation in
      the breast. We assessed the levels of each ER in normal mouse mammary glands
      subdivided into proliferative and non-proliferative regions. ERalpha was most
      abundant in the proliferative regions of younger mice, with ERbeta expressed most
      abundantly in old mice. We correlated this expression profile with function by
      showing that the ability of estrogen to induce proliferation was reduced in older
      mice. To show that the ER profile associated with breast cancer risk, we assessed
      ER expression in parous mice which are known to have a reduced risk of developing
      ERalpha breast cancer. ERalpha expression was significantly decreased yet co
      localization analysis revealed ERbeta expression increased with parity. Parous
      mice had less unopposed nuclear ERalpha expression and increased levels of
      ERbeta. These changes suggest that the nuclear expression of ERs dictates the
      proliferative nature of the breast and may explain the decreased breast cancer
      risk with parity.

PMID- 29636365
TI  - Predictors of Oophorectomy in Girls Hospitalized in Texas With Ovarian Torsion.
AB  - OBJECTIVES: Inconsistent results have been reported by authors of studies of the
      management of pediatric patients with ovarian torsion (OT). Our objective was to
      identify predictors of oophorectomy in girls hospitalized throughout Texas with
      OT. METHODS: The Texas Public Use Data File (years 2013-2014) was queried for the
      records of girls under the age of 18 years who had a principal or secondary
      discharge diagnosis of OT (International Classification of Diseases, Ninth
      Revision, Clinical Modification code 620.5). Adjusted odds ratios were estimated
      from a logistic regression model by using Firth's bias-reducing penalized
      likelihood. Variables for inclusion in the final model were identified by using a
      directed acyclic graph. RESULTS: A sample of 158 girls was identified with an
      overall risk of oophorectomy during the hospital stay of 41.1% (65 out of 158).
      After adjusting for the patient's age, health insurance status, and the presence
      of an ovarian cyst, girls who were treated at a nonteaching hospital were more
      than twice as likely to undergo oophorectomy than girls who were treated at a
      teaching hospital (odds ratio = 2.22; 95% confidence interval: 1.05-4.69).
      CONCLUSIONS: Our analysis of a statewide database revealed that girls with OT who
      presented at nonteaching hospitals were significantly more likely to undergo
      oophorectomy compared with girls who presented at teaching hospitals.

PMID- 29636364
TI  - Bufalin suppresses endometriosis progression by inducing pyroptosis and
      apoptosis.
AB  - The steroid receptor coactivator (SRC)-1 isoform/estrogen receptor (ER)-beta axis
      has an essential role in endometriosis progression. In this context, therefore,
      bufalin was employed as a 'tool compound' to evaluate inhibitors of SRC in
      alternative endometriosis treatment. Bufalin effectively suppressed the growth of
      primary human endometrial stroma cells isolated from endometriosis patients
      compared to women without endometriosis and immortalized human endometrial
      epithelial and stromal cells expressing the SRC-1 isoform compared to their
      parental cells in vitroIn vivo, compared to the vehicle, bufalin treatment
      significantly suppressed the growth of endometriotic lesions in mice with
      surgically induced endometriosis because bufalin disrupted the functional axis of
      SRC-1 isoform/ERbeta by increasing SRC-1 isoform protein stability,
      hyperactivating the transcriptional activity of the SRC-1 isoform and degrading
      the ERbeta protein by proteasome 26S subunit, non-ATPase 2 in endometriotic
      lesions. Bufalin treatment elevated the apoptosis signaling in epithelial cells
      of endometriotic lesions. In stromal cells of endometriotic lesions, bufalin
      treatment increased the levels of pyroptosis markers (caspase 1 and the active
      form of interleukin 1beta) and reduced proliferation. In addition, bufalin
      treatment increased the expression levels of endoplasmic reticulum-stress (ERS)
      markers (PKR-like ER kinase, protein disulfide isomerase and binding
      immunoglobulin) in endometriotic lesions. Collectively, the bufalin-induced
      disruption of the SRC-1 isoform/ERbeta axis might induce apoptosis, pyroptosis
      and ERS signaling in endometriotic lesions, causing the suppression of
      endometriosis. Therefore, future generations of SRC-modulators could be employed
      as an alternative medical approach for endometriosis treatment.

PMID- 29636366
TI  - Adipocyte-specific DKO of Lkb1 and mTOR protects mice against HFD-induced
      obesity, but results in insulin resistance.
AB  - Liver kinase B1 (Lkb1) and mammalian target of rapamycin (mTOR) are key
      regulators of energy metabolism and cell growth. We have previously reported that
      adipocyte-specific KO of Lkb1 or mTOR in mice results in distinct developmental
      and metabolic phenotypes. Here, we aimed to assess how genetic KO of both Lkb1
      and mTOR affects adipose tissue development and function in energy homeostasis.
      We used Adiponectin-Cre to drive adipocyte-specific double KO (DKO) of Lkb1 and
      mTOR in mice. We performed indirect calorimetry, glucose and insulin tolerance
      tests, and gene expression assays on the DKO and WT mice. We found that DKO of
      Lkb1 and mTOR results in reductions of brown adipose tissue and inguinal white
      adipose tissue mass, but in increases of liver mass. Notably, the DKO mice
      developed fatty liver and insulin resistance, but displayed improved glucose
      tolerance after high-fat diet (HFD)-feeding. Interestingly, the DKO mice were
      protected from HFD-induced obesity due to their higher energy expenditure and
      lower expression levels of adipogenic genes (CCAAT/enhancer binding protein alpha
      and PPARgamma) compared with WT mice. These results together indicate that,
      compared with Lkb1 or mTOR single KOs, Lkb1/mTOR DKO in adipocytes results in
      overlapping and distinct metabolic phenotypes, and mTOR KO largely overrides the
      effect of Lkb1 KO.

PMID- 29636368
TI  - Combining chloroquine with RAD001 inhibits tumor growth in a NEN mouse model.
AB  - Patients with neuroendocrine neoplasms (NENs) often require systemic treatment,
      which is frequently limited by the emergence of drug resistance. mTOR inhibitors
      (mTORi), such as RAD001 (everolimus), have been shown to inhibit neoplasm
      progression. mTORi stimulates autophagy, a degradation pathway that might promote
      the survival of neoplasm cells that are exposed to anti-cancer therapy.
      Chloroquine (CQ), a well-known anti-malarial and anti-rheumatic drug, suppresses
      autophagy. Based on our previous results, we hypothesized that CQ may enhance the
      anti-tumorigenic effects of mTORi by inhibiting autophagy and we aimed to examine
      the anti-tumorigenic effect of CQ, alone or in combination with RAD001. We
      established a NEN subcutaneous xenograft mouse model and evaluated the effect of
      the drugs on tumor growth, mTOR pathway, autophagy and apoptosis. CQ alone and in
      combination with RAD001 significantly decreased neoplasm volume.
      Histopathological analysis revealed that the combination of CQ and RAD001
      markedly inhibited mTOR activity and neoplasm cell growth, along with
      accumulation of autophagosomes and increased apoptosis. In conclusion, CQ
      enhances the anti-tumorigenic effect of RAD001 in vivo by inhibiting autophagy.
      Clinical trials addressing the effects of CQ therapy on neoplasm progression in
      patients with NENs, mainly in those treated with mTORi, are warranted.

PMID- 29636367
TI  - Disruption of NSD1 in Head and Neck Cancer Promotes Favorable Chemotherapeutic
      Responses Linked to Hypomethylation.
AB  - Human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC)
      represents a distinct classification of cancer with worse expected outcomes. Of
      the 11 genes recurrently mutated in HNSCC, we identify a singular and substantial
      survival advantage for mutations in the gene encoding Nuclear Set Domain
      Containing Protein 1 (NSD1), a histone methyltransferase altered in approximately
      10% of patients. This effect, a 55% decrease in risk of death in NSD1-mutated
      versus non-mutated patients, can be validated in an independent cohort. NSD1
      alterations are strongly associated with widespread genome hypomethylation in the
      same tumors, to a degree not observed for any other mutated gene. To address
      whether NSD1 plays a causal role in these associations, we use CRISPR-Cas9 to
      disrupt NSD1 in HNSCC cell lines and find that this leads to substantial CpG
      hypomethylation and sensitivity to cisplatin, a standard chemotherapy in head and
      neck cancer, with a 40% to 50% decrease in the IC50 value. Such results are
      reinforced by a survey of 1,001 cancer cell lines, in which loss-of-function NSD1
      mutations have an average 23% decrease in cisplatin IC50 value compared with cell
      lines with wild-type NSD1Significance: This study identifies a favorable subtype
      of HPV-negative HNSCC linked to NSD1 mutation, hypomethylation, and cisplatin
      sensitivity. Mol Cancer Ther; 17(7); 1585-94. (c)2018 AACR.

PMID- 29636370
TI  - The tongue as a gripper.
AB  - Frogs, chameleons and anteaters are striking examples of animals that can grab
      food using only their tongue. How does the soft and wet surface of a tongue grip
      onto objects before they are ingested? Here, we review the diversity of tongue
      projection methods, tongue roughnesses and tongue coatings, our goal being to
      highlight conditions for effective grip and mobility. A softer tongue can reach
      farther: the frog Rana pipiens tongue is 10 times softer than the human tongue
      and can extend to 130% of its length when propelled in a whip-like motion.
      Roughness can improve a tongue's grip: the spikes on a penguin Eudyptes
      chrysolophus tongue can be as large as fingernails, and help the penguin swallow
      fish. The saliva coating on the tongue, a non-Newtonian biofluid, can either
      lubricate or adhere to food. Frog saliva is 175 times more viscous than human
      saliva, adhering the tongue to slippery, furry or feathery food. We pay
      particular attention to using mathematical models such as the theory of
      capillarity, elasticity and friction to elucidate the parameters for effective
      tongue use across a variety of vertebrate species. Finally, we postulate how the
      use of wet and rough surfaces to simultaneously sense and grip may inspire new
      strategies in emerging technologies such as soft robots.

PMID- 29636369
TI  - Differential Expression of Histone H3.3 Genes and Their Role in Modulating
      Temperature Stress Response in Caenorhabditis elegans.
AB  - Replication-independent variant histones replace canonical histones in
      nucleosomes and act as important regulators of chromatin function. H3.3 is a
      major variant of histone H3 that is remarkably conserved across taxa and is
      distinguished from canonical H3 by just four key amino acids. Most genomes
      contain two or more genes expressing H3.3, and complete loss of the protein
      usually causes sterility or embryonic lethality. Here, we investigate the
      developmental expression patterns of the five Caenorhabditis elegans H3.3
      homologs and identify two previously uncharacterized homologs to be restricted to
      the germ line. Despite these specific expression patterns, we find that neither
      loss of individual H3.3 homologs nor the knockout of all five H3.3-coding genes
      causes sterility or lethality. However, we demonstrate an essential role for the
      conserved histone chaperone HIRA in the nucleosomal loading of all H3.3 variants.
      This requirement can be bypassed by mutation of the H3.3-specific residues to
      those found in H3. While even removal of all H3.3 homologs does not result in
      lethality, it leads to reduced fertility and viability in response to high
      temperature stress. Thus, our results show that H3.3 is nonessential in C.
      elegans but is critical for ensuring adequate response to stress.

PMID- 29636371
TI  - Repeat-mediated deletions can be induced by a chromosomal break far from a
      repeat, but multiple pathways suppress such rearrangements.
AB  - Chromosomal deletion rearrangements mediated by repetitive elements often involve
      repeats separated by several kilobases and sequences that are divergent. While
      such rearrangements are likely induced by DNA double-strand breaks (DSBs), it has
      been unclear how the proximity of DSBs relative to repeat sequences affects the
      frequency of such events. We generated a reporter assay in mouse cells for a
      deletion rearrangement involving repeats separated by 0.4 Mb. We induced this
      repeat-mediated deletion (RMD) rearrangement with two DSBs: the 5' DSB that is
      just downstream from the first repeat and the 3' DSB that is varying distances
      upstream of the second repeat. Strikingly, we found that increasing the 3'
      DSB/repeat distance from 3.3 kb to 28.4 kb causes only a modest decrease in
      rearrangement frequency. We also found that RMDs are suppressed by KU70 and RAD51
      and promoted by RAD52, CtIP, and BRCA1. In addition, we found that 1%-3% sequence
      divergence substantially suppresses these rearrangements in a manner dependent on
      the mismatch repair factor MSH2, which is dominant over the suppressive role of
      KU70. We suggest that a DSB far from a repeat can stimulate repeat-mediated
      rearrangements, but multiple pathways suppress these events.

PMID- 29636372
TI  - Role of high-throughput sequencing in the diagnosis of cutaneous T-cell lymphoma.
AB  - AIMS: Substantial clinicopathological overlap exists between cutaneous T-cell
      lymphoma (CTCL) and benign conditions, leading to diagnostic difficulties. We
      sought to delineate the utility of high-throughput sequencing (HTS) across a
      spectrum of histological findings in CTCL and reactive mimics. METHODS: One
      hundred skin biopsies obtained for clinical concern for CTCL were identified,
      comprising 25 cases each from four histological categories: 'definitive CTCL',
      'atypical lymphoid infiltrate, concerning for CTCL', 'atypical lymphoid
      infiltrate, favour reactive' or 'reactive lymphoid infiltrate'. T-cell receptor
      gamma chain gene (TRG) PCR and T-cell receptor beta chain gene HTS were performed
      on both skin biopsy and concurrently collected peripheral blood; most peripheral
      blood samples were also analysed by flow cytometry. RESULTS: Histologically
      defined CTCL specimens had significantly higher clonality scores and T-cell
      fractions via HTS than all other groups (all p<0.002 and p<0.03, respectively).
      HTS was more diagnostically specific than TRG PCR in skin (100% vs 88%), while
      diagnostic sensitivity (68% vs 72%) and accuracy (84% vs 80%) were similar. TRG
      PCR and flow cytometry performed on blood were the least diagnostically useful
      assays. Some identically sized peaks detected by TRG PCR in concurrent skin and
      peripheral blood specimens were non-identical by HTS analysis. CONCLUSIONS: HTS,
      by assessing both clonality and T-cell fractions in skin biopsies, is a powerful
      tool to aid in the diagnosis of CTCL. It is more specific than TRG PCR in
      distinguishing definitive CTCL from reactive and indeterminate histology.
      Identically sized peaks by TRG PCR, typically interpreted to be clonally related,
      are not always clonally identical by sequencing.

PMID- 29636373
TI  - Germline deletion of CIN85 in humans with X chromosome-linked antibody
      deficiency.
AB  - Ubiquitously expressed Cbl-interacting protein of 85 kD (CIN85) is a
      multifunctional adapter molecule supposed to regulate numerous cellular processes
      that are critical for housekeeping as well as cell type-specific functions.
      However, limited information exists about the in vivo roles of CIN85, because
      only conditional mouse mutants with cell type-specific ablation of distinct CIN85
      isoforms in brain and B lymphocytes have been generated so far. No information is
      available about the roles of CIN85 in humans. Here, we report on primary antibody
      deficiency in patients harboring a germline deletion within the CIN85 gene on the
      X chromosome. In the absence of CIN85, all immune cell compartments developed
      normally, but B lymphocytes showed intrinsic defects in distinct effector
      pathways of the B cell antigen receptor, most notably NF-kappaB activation and up
      regulation of CD86 expression on the cell surface. These results reveal
      nonredundant functions of CIN85 for humoral immune responses.

PMID- 29636375
TI  - Tourette's syndrome and its borderland.
AB  - The Gilles de la Tourette syndrome (or Tourette's syndrome) has a prevalence of
      1% of children with a wide range of severity and associated comorbidities. The
      last 20 years have seen advances in the understanding of the syndrome's complex
      genetics and underlying neurobiology. Investigation with imaging and
      neurophysiology techniques indicate it is a neurodevelopmental condition with
      dysfunction of basal ganglia-cortical interactions, which are now also being
      studied in animal models. There is also increasing evidence for treatments
      although it often remains difficult to manage. First-line options include
      neuroleptics, other drugs and specialised behavioural treatments. Deep brain
      stimulation is an evolving field, not yet fully established. This review focuses
      on the phenomenology of tics, how to assess and manage the syndrome, and uses
      examples of atypical cases to explore the characteristics and limits of its
      clinical spectrum.

PMID- 29636374
TI  - Mutational signatures of DNA mismatch repair deficiency in C. elegans and human
      cancers.
AB  - Throughout their lifetime, cells are subject to extrinsic and intrinsic
      mutational processes leaving behind characteristic signatures in the genome. DNA
      mismatch repair (MMR) deficiency leads to hypermutation and is found in different
      cancer types. Although it is possible to associate mutational signatures
      extracted from human cancers with possible mutational processes, the exact
      causation is often unknown. Here, we use C. elegans genome sequencing of pms-2
      and mlh-1 knockouts to reveal the mutational patterns linked to C. elegans MMR
      deficiency and their dependency on endogenous replication errors and errors
      caused by deletion of the polymerase epsilon subunit pole-4 Signature extraction
      from 215 human colorectal and 289 gastric adenocarcinomas revealed three MMR
      associated signatures, one of which closely resembles the C. elegans MMR spectrum
      and strongly discriminates microsatellite stable and unstable tumors (AUC = 98%).
      A characteristic difference between human and C. elegans MMR deficiency is the
      lack of elevated levels of NCG > NTG mutations in C. elegans, likely caused by
      the absence of cytosine (CpG) methylation in worms. The other two human MMR
      signatures may reflect the interaction between MMR deficiency and other mutagenic
      processes, but their exact cause remains unknown. In summary, combining
      information from genetically defined models and cancer samples allows for better
      aligning mutational signatures to causal mutagenic processes.

PMID- 29636376
TI  - Drug Transporters in Xenobiotic Disposition and Pharmacokinetic Prediction.
AB  - Drug transporters are widely expressed in organs and tissue barriers throughout
      human and animal bodies. Studies over the last two decades have identified
      various ATP-binding cassette and solute carrier transporters that play critical
      roles in the absorption, distribution, metabolism, and elimination of drugs and
      xenobiotics. This special section contains more than 20 original manuscripts and
      reviews that cover the most recent advances in the areas of drug transporter
      research, including the basic biology and function of transporters, expression of
      drug transporters in organ and tissue barriers, the mechanisms underlying
      regulation of transporter expression, transporter-mediated drug disposition in
      animal models, and the development and utilization of new technologies in drug
      transporter study, as well as pharmacokinetic modeling and simulation to assess
      transporter involvement in drug disposition and drug-drug interactions. We
      believe that the topics covered in this special section will advance our
      understanding of the roles of transporters in drug disposition, efficacy, and
      safety.

PMID- 29636377
TI  - Identification of Global and Ligand-Specific Calcium Sensing Receptor Activation
      Mechanisms.
AB  - Calcium sensing receptor (CaSR) positive allosteric modulators (PAMs) are
      therapeutically important. However, few are approved for clinical use, in part
      due to complexities in assessing allostery at a receptor where the endogenous
      agonist (extracellular calcium) is present in all biologic fluids. Such
      complexity impedes efforts to quantify and optimize allosteric drug parameters
      (affinity, cooperativity, and efficacy) that dictate PAM structure-activity
      relationships (SARs). Furthermore, an underappreciation of the structural
      mechanisms underlying CaSR activation hinders predictions of how PAM SAR relates
      to in vitro and in vivo activity. Herein, we combined site-directed mutagenesis
      and calcium mobilization assays with analytical pharmacology to compare modes of
      PAM binding, positive modulation, and agonism. We demonstrate that 3-(2
      chlorophenyl)-N-((1R)-1-(3-methoxyphenyl)ethyl)-1-propanamine (NPS R568) binds to
      a 7 transmembrane domain (7TM) cavity common to class C G protein-coupled
      receptors and used by (alphaR)-(-)-alpha-methyl-N-[3-[3
      [trifluoromethylphenyl]propyl]-1-napthalenemethanamine (cinacalcet) and 1
      benzothiazol-2-yl-1-(2,4-dimethylphenyl)-ethanol (AC265347); however, there are
      subtle distinctions in the contribution of select residues to the binding and
      transmission of cooperativity by PAMs. Furthermore, we reveal some common
      activation mechanisms used by different CaSR activators, but also demonstrate
      some differential contributions of residues within the 7TM bundle and
      extracellular loops to the efficacy of the PAM-agonist, AC265347, versus
      cooperativity. Finally, we show that PAMS potentiate the affinity of divalent
      cations. Our results support the existence of both global and ligand-specific
      CaSR activation mechanisms and reveal that allosteric agonism is mediated in part
      via distinct mechanisms to positive modulation.

PMID- 29636379
TI  - The DEAD-box RNA helicase Ddx39ab is essential for myocyte and lens development
      in zebrafish.
AB  - RNA helicases from the DEAD-box family are found in almost all organisms and have
      important roles in RNA metabolism, including RNA synthesis, processing and
      degradation. The function and mechanism of action of most of these helicases in
      animal development and human disease remain largely unexplored. In a zebrafish
      mutagenesis screen to identify genes essential for heart development we
      identified a mutant that disrupts the gene encoding the RNA helicase DEAD-box
      39ab (ddx39ab). Homozygous ddx39ab mutant embryos exhibit profound cardiac and
      trunk muscle dystrophy, along with lens abnormalities, caused by abrupt terminal
      differentiation of cardiomyocyte, myoblast and lens fiber cells. Loss of ddx39ab
      hindered splicing of mRNAs encoding epigenetic regulatory factors, including
      members of the KMT2 gene family, leading to misregulation of structural gene
      expression in cardiomyocyte, myoblast and lens fiber cells. Taken together, these
      results show that Ddx39ab plays an essential role in establishment of the proper
      epigenetic status during differentiation of multiple cell lineages.

PMID- 29636378
TI  - Cardiac c-Kit Biology Revealed by Inducible Transgenesis.
AB  - RATIONALE: Biological significance of c-Kit as a cardiac stem cell marker and
      role(s) of c-Kit+ cells in myocardial development or response to pathological
      injury remain unresolved because of varied and discrepant findings. Alternative
      experimental models are required to contextualize and reconcile discordant
      published observations of cardiac c-Kit myocardial biology and provide meaningful
      insights regarding clinical relevance of c-Kit signaling for translational cell
      therapy. OBJECTIVE: The main objectives of this study are as follows:
      demonstrating c-Kit myocardial biology through combined studies of both human and
      murine cardiac cells; advancing understanding of c-Kit myocardial biology through
      creation and characterization of a novel, inducible transgenic c-Kit reporter
      mouse model that overcomes limitations inherent to knock-in reporter models; and
      providing perspective to reconcile disparate viewpoints on c-Kit biology in the
      myocardium. METHODS AND RESULTS: In vitro studies confirm a critical role for c
      Kit signaling in both cardiomyocytes and cardiac stem cells. Activation of c-Kit
      receptor promotes cell survival and proliferation in stem cells and
      cardiomyocytes of either human or murine origin. For creation of the mouse model,
      the cloned mouse c-Kit promoter drives Histone2B-EGFP (enhanced green fluorescent
      protein; H2BEGFP) expression in a doxycycline-inducible transgenic reporter line.
      The combination of c-Kit transgenesis coupled to H2BEGFP readout provides
      sensitive, specific, inducible, and persistent tracking of c-Kit promoter
      activation. Tagging efficiency for EGFP+/c-Kit+ cells is similar between our
      transgenic versus a c-Kit knock-in mouse line, but frequency of c-Kit+ cells in
      cardiac tissue from the knock-in model is 55% lower than that from our transgenic
      line. The c-Kit transgenic reporter model reveals intimate association of c-Kit
      expression with adult myocardial biology. Both cardiac stem cells and a
      subpopulation of cardiomyocytes express c-Kit in uninjured adult heart,
      upregulating c-Kit expression in response to pathological stress. CONCLUSIONS: c
      Kit myocardial biology is more complex and varied than previously appreciated or
      documented, demonstrating validity in multiple points of coexisting yet
      heretofore seemingly irreconcilable published findings.

PMID- 29636381
TI  - aPKC is a key polarity determinant in coordinating the function of three distinct
      cell polarities during collective migration.
AB  - Apical-basal polarity is a hallmark of epithelia and needs to be remodeled when
      epithelial cells undergo morphogenetic cell movements. Here, we analyze border
      cells in the Drosophila ovary to address how apical-basal polarity is remodeled
      and turned into front-back and inside-outside as well as apical-basal polarities,
      during collective migration. We find that the Crumbs (Crb) complex is required
      for the generation of the three distinct but interconnected cell polarities of
      border cells. Specifically, the Crb complex, together with the Par complex and
      the endocytic recycling machinery, ensures the strict distribution of two
      distinct populations of aPKC at the inside apical junction and near the outside
      lateral membrane. Interestingly, aPKC distributed near the outside lateral
      membrane interacts with Sif and promotes Rac-induced protrusions, whereas
      alteration of the aPKC distribution pattern changes the pattern of protrusion
      formation, leading to disruption of all three polarities. Therefore, we
      demonstrate that aPKC, spatially controlled by the Crb complex, is a key polarity
      molecule coordinating the generation of three distinct but interconnected cell
      polarities during collective migration.

PMID- 29636380
TI  - The non-canonical Wnt-PCP pathway shapes the mouse caudal neural plate.
AB  - The last stage of neural tube (NT) formation involves closure of the caudal
      neural plate (NP), an embryonic structure formed by neuromesodermal progenitors
      and newly differentiated cells that becomes incorporated into the NT. Here, we
      show in mouse that, as cell specification progresses, neuromesodermal progenitors
      and their progeny undergo significant changes in shape prior to their
      incorporation into the NT. The caudo-rostral progression towards differentiation
      is coupled to a gradual reliance on a unique combination of complex mechanisms
      that drive tissue folding, involving pulses of apical actomyosin contraction and
      planar polarised cell rearrangements, all of which are regulated by the Wnt-PCP
      pathway. Indeed, when this pathway is disrupted, either chemically or
      genetically, the polarisation and morphology of cells within the entire caudal NP
      is disturbed, producing delays in NT closure. The most severe disruptions of this
      pathway prevent caudal NT closure and result in spina bifida. In addition, a
      decrease in Vangl2 gene dosage also appears to promote more rapid progression
      towards a neural fate, but not the specification of more neural cells.

PMID- 29636382
TI  - High prevalence rate of digestive tract bacteria in duodenoscopes: a nationwide
      study.
AB  - OBJECTIVE: Increasing numbers of outbreaks caused by contaminated duodenoscopes
      used for Endoscopic Retrograde Cholangiopancreatography (ERCP) procedures have
      been reported, some with fatal outcomes. We conducted a nationwide cross
      sectional study to determine the prevalence of bacterial contamination of
      reprocessed duodenoscopes in The Netherlands. DESIGN: All 73 Dutch ERCP centres
      were invited to sample >=2 duodenoscopes using centrally distributed kits
      according to uniform sampling methods, explained by video instructions. Depending
      on duodenoscope type, four to six sites were sampled and centrally cultured.
      Contamination was defined as (1) any microorganism with >=20 colony forming units
      (CFU)/20 mL (AM20) and (2) presence of microorganisms with gastrointestinal or
      oral origin, independent of CFU count (MGO). RESULTS: Sixty-seven out of 73
      centres (92%) sampled 745 sites of 155 duodenoscopes. Ten different duodenoscope
      types from three distinct manufacturers were sampled including 69 (46%) Olympus
      TJF-Q180V, 43 (29%) Olympus TJF-160VR, 11 (7%) Pentax ED34-i10T, 8 (5%) Pentax ED
      3490TK and 5 (3%) Fujifilm ED-530XT8. Thirty-three (22%) duodenoscopes from 26
      (39%) centres were contaminated (AM20). On 23 (15%) duodenoscopes MGO were
      detected, including Enterobacter cloacae, Escherichia coli, Klebsiella pneumonia
      and yeasts. For both definitions, contamination was not duodenoscope type
      dependent (p values: 0.20 and higher). CONCLUSION: In 39% of all Dutch ERCP
      centres, at least one AM20-contaminated patient-ready duodenoscope was
      identified. Fifteen per cent of the duodenoscopes harboured MGO, indicating
      residual organic material of previous patients, that is, failing of disinfection.
      These results suggest that the present reprocessing and process control
      procedures are not adequate and safe.

PMID- 29636384
TI  - Trainees success rates with intubation to suction meconium at birth.
AB  - OBJECTIVES: To assess the success rate and main reasons for failure of intubation
      performed by medical trainees to suction meconium below the vocal cords in non
      vigorous infants delivered at >=36 week gestation. DESIGN: We conducted a
      prospective cohort study involving 54 residents and nine neonatology fellows in a
      Canadian level 3 neonatal intensive care unit. Endotracheal intubation to suction
      meconium was performed using a videolaryngoscope, the video screen being covered
      during the procedure. All videos were reviewed by two experts blinded to the
      procedure and to the identity of the trainee. RESULTS: Sixteen videos were
      available to review between July 2014 and March 2016. Intubation success rate
      assessed by the reviewers was 6%, compared with 21% as assessed by the trainees.
      The most common reasons for intubation failure were an improper view of the
      glottis (87%) and meconium or secretions obscuring the view (67%). 36 % of the
      time, the trainees identified different reasons for intubation failure than the
      reviewers. CONCLUSION: Success rate of neonatal intubation to suction meconium
      was much lower than the success rate reported on infants without meconium.
      Teaching should be geared towards the most common reasons for intubation failure,
      possibly using video-based teaching.

PMID- 29636383
TI  - Colesevelam attenuates cholestatic liver and bile duct injury in Mdr2-/- mice by
      modulating composition, signalling and excretion of faecal bile acids.
AB  - BACKGROUND AND AIMS: Interruption of the enterohepatic circulation of bile acids
      (BAs) may protect against BA-mediated cholestatic liver and bile duct injury. BA
      sequestrants are established to treat cholestatic pruritus, but their impact on
      the underlying cholestasis is still unclear. We aimed to explore the therapeutic
      effects and mechanisms of the BA sequestrant colesevelam in a mouse model of
      sclerosing cholangitis. METHODS: Mdr2-/- mice received colesevelam for 8 weeks.
      Gene expression profiles of BA homeostasis, inflammation and fibrosis were
      explored in liver, intestine and colon. Hepatic and faecal BA profiles and gut
      microbiome were analysed. Glucagon-like peptide 1 (GLP-1) levels in portal blood
      were measured by ELISA. Furthermore, Mdr2-/- mice as well as wild-type 3,5
      diethoxy-carbonyl-1,4-dihydrocollidine-fed mice were treated with GLP-1-receptor
      agonist exendin-4 for 2 weeks prior to analysis. RESULTS: Colesevelam reduced
      serum liver enzymes, BAs and expression of proinflammatory and profibrogenic
      markers. Faecal BA profiling revealed increased levels of secondary BAs after
      resin treatment, while hepatic and biliary BA composition showed a shift towards
      more hydrophilic BAs. Colonic GLP-1 secretion, portal venous GLP-1 levels and
      intestinal messenger RNA expression of gut hormone Proglucagon were increased,
      while ileal Fgf15 expression was abolished by colesevelam. Exendin-4 treatment
      increased bile duct mass without promoting a reactive cholangiocyte phenotype in
      mouse models of sclerosing cholangitis. Microbiota analysis showed an increase of
      the phylum delta-Proteobacteria after colesevelam treatment and a shift within
      the phyla Firmicutes from Clostridiales to Lactobacillus. CONCLUSION: Colesevelam
      increases faecal BA excretion and enhances BA conversion towards secondary BAs,
      thereby stimulating secretion of GLP-1 from enteroendocrine L-cells and
      attenuates liver and bile duct injury in Mdr2-/- mice.

PMID- 29636385
TI  - Safety of meningococcal group B vaccination in hospitalised premature infants.
AB  - OBJECTIVES: To assess the risk of significant adverse events in premature infants
      receiving the novel 4-component group B meningococcal vaccine (4CMenB) with their
      routine immunisations at 2 months of age. PARTICIPANTS, DESIGN AND SETTING: In
      December 2015, Public Health England requested neonatal units across England to
      voluntarily participate in a national audit; 19 units agreed to participate.
      Anonymised questionnaires were completed for infants receiving 4CMenB alongside
      their routine immunisations. For comparison, a historical cohort of premature
      infants receiving their primary immunisations without 4CMenB or paracetamol
      prophylaxis was used. MAIN OUTCOME MEASURES: Paracetamol use; temperature,
      cardiovascular, respiratory and neurological status before and after vaccination;
      and management and investigations postvaccination, including serum C reactive
      protein levels, infection screens and antibiotic use. RESULTS: Complete
      questionnaires were returned for 133 premature infants (<35 weeks' gestation) who
      received their first dose of 4CMenB at 8 weeks of age, including 108 who received
      prophylactic paracetamol according to national recommendations. Overall, 7%
      (8/108) of infants receiving 4CMenB with paracetamol had fever (>38 degrees C)
      after vaccination compared with 20% (5/25) of those receiving 4CMenB without
      paracetamol (P=0.06) and none of those in the historical cohort. There were no
      significant differences between cohorts in the proportion of infants with apnoea,
      bradycardia, desaturation and receiving respiratory support after vaccination.
      CONCLUSIONS: 4CMenB does not increase the risk of serious adverse events in
      hospitalised premature infants. This audit supports the current national
      recommendations to offer 4CMenB with other routine vaccinations and prophylactic
      paracetamol to premature infants at their chronological age.

PMID- 29636386
TI  - Insights into CKD from Metabolite GWAS.

PMID- 29636387
TI  - Depletion of Gprc5a Promotes Development of Diabetic Nephropathy.
AB  - Background Renal glomeruli are the primary target of injury in diabetic
      nephropathy (DN), and the glomerular podocyte has a key role in disease
      progression.Methods To identify potential novel therapeutic targets for DN, we
      performed high-throughput molecular profiling of G protein-coupled receptors
      (GPCRs) using human glomeruli.Results We identified an orphan GPCR, Gprc5a, as a
      highly podocyte-specific gene, the expression of which was significantly
      downregulated in glomeruli of patients with DN compared with those without DN.
      Inactivation of Gprc5a in mice resulted in thickening of the glomerular basement
      membrane and activation of mesangial cells, which are two hallmark features of DN
      in humans. Compared with wild-type mice, Gprc5a-deficient animals demonstrated
      increased albuminuria and more severe histologic changes after induction of
      diabetes with streptozotocin. Mechanistically, Gprc5a modulated TGF-beta
      signaling and activation of the EGF receptor in cultured podocytes.Conclusions
      Gprc5a has an important role in the pathogenesis of DN, and further study of the
      podocyte-specific signaling activity of this protein is warranted.

PMID- 29636388
TI  - Architecture of the complete oxygen-sensing FixL-FixJ two-component signal
      transduction system.
AB  - The symbiotic nitrogen-fixing bacterium Bradyrhizobium japonicum is critical to
      the agro-industrial production of soybean because it enables the production of
      high yields of soybeans with little use of nitrogenous fertilizers. The FixL and
      FixJ two-component system (TCS) of this bacterium ensures that nitrogen fixation
      is only stimulated under conditions of low oxygen. When it is not bound to
      oxygen, the histidine kinase FixL undergoes autophosphorylation and transfers
      phosphate from adenosine triphosphate (ATP) to the response regulator FixJ,
      which, in turn, stimulates the expression of genes required for nitrogen
      fixation. We purified full-length B. japonicum FixL and FixJ proteins and defined
      their structures individually and in complex using small-angle x-ray scattering,
      crystallographic, and in silico modeling techniques. Comparison of active and
      inactive forms of FixL suggests that intramolecular signal transduction is driven
      by local changes in the sensor domain and in the coiled-coil region connecting
      the sensor and histidine kinase domains. We also found that FixJ exhibits
      conformational plasticity not only in the monomeric state but also in tetrameric
      complexes with FixL during phosphotransfer. This structural characterization of a
      complete TCS contributes both a mechanistic and evolutionary understanding to TCS
      signal relay, specifically in the context of the control of nitrogen fixation in
      root nodules.

PMID- 29636389
TI  - The nuclear translocation of the kinases p38 and JNK promotes inflammation
      induced cancer.
AB  - The stimulated nuclear translocation of signaling proteins, such as MAPKs, is a
      necessity for the initiation and regulation of their physiological functions.
      Previously, we determined that nuclear translocation of the MAPKs p38 and JNK
      involves binding to heterodimers comprising importin 3 and either importin 7 or
      importin 9. Here, we identified the importin-binding region in p38 and JNK and
      developed a myristoylated peptide targeting this site that we called PERY. The
      PERY peptide specifically blocked the interaction of p38 and JNK with the
      importins, restricted their nuclear translocation, and inhibited phosphorylation
      of their nuclear (but not cytoplasmic) substrates. Through these effects, the
      PERY peptide reduced the proliferation of several (but not all) cancer cell lines
      in culture and inhibited the growth of a human breast cancer xenograft in mice.
      In addition, the PERY peptide substantially inhibited inflammation in mice, as
      manifested in models of colitis and colitis-associated colon cancer. The PERY
      peptide more effectively prevented colon cancer development than did a commercial
      p38 inhibitor. In vivo analysis further suggested that this effect was mediated
      by PERY peptide-induced prevention of the nuclear translocation of p38 in
      macrophages. Together, these results support the use of the nuclear translocation
      of p38 and JNK as a novel drug target to treat various cancers and inflammation
      induced diseases.

PMID- 29636390
TI  - A nanoscale reorganization of the IL-15 receptor is triggered by NKG2D in a
      ligand-dependent manner.
AB  - Natural killer group 2D (NKG2D), an activating receptor on natural killer (NK)
      cells and a subset of T cells, recognizes stress-inducible proteins, including
      MICA and ULBP2, which are present on infected or transformed cells. Whether each
      NKG2D ligand (NKG2DL) has a distinct biological role is not clear. Using
      superresolution microscopy, we found that NKG2D is constitutively arranged in
      nanoclusters at the surface of human primary NK cells. Nanoclusters of NKG2D
      became smaller upon ligation with MICA but became larger upon activation by
      ULBP2. In addition, ULBP2 induced the reorganization of nanoclusters of the
      cytokine receptor subunit for both interleukin-2 (IL-2) and IL-15 (IL-2/IL
      15Rbeta), such that these cytokine receptor subunits coalesced with nanoclusters
      of NKG2D. Functionally, the response of NK cells activated by ULBP2 was augmented
      by an interaction between ULBP2-bound NKG2D and IL-15R ligated by IL-15 (trans
      presented by IL-15Ralpha-coated surfaces). These data suggest that NKG2DLs are
      not equivalent in their capacity to activate NKG2D and establish a previously
      unknown paradigm in how ligand-induced changes to the nanoscale organization of
      the cell surface can affect immune responses.

PMID- 29636391
TI  - mTORC1 controls lysosomal Ca2+ release through the two-pore channel TPC2.
AB  - Two-pore segment channel 2 (TPC2) is a ubiquitously expressed, lysosomally
      targeted ion channel that aids in terminating autophagy and is inhibited upon its
      association with mechanistic target of rapamycin (mTOR). It is controversial
      whether TPC2 mediates lysosomal Ca2+ release or selectively conducts Na+ and
      whether the binding of nicotinic acid adenine dinucleotide phosphate (NAADP) or
      phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2] is required for the activity of
      this ion channel. We show that TPC2 is required for intracellular Ca2+ signaling
      in response to NAADP or to mTOR inhibition by rapamycin. In pulmonary arterial
      myocytes, rapamycin and NAADP evoked global Ca2+ transients that were blocked by
      depletion of lysosomal Ca2+ stores. Preincubation of cells with high
      concentrations of rapamycin resulted in desensitization and blocked NAADP-evoked
      Ca2+ signals. Moreover, rapamycin and NAADP did not evoke discernable Ca2+
      transients in myocytes derived from Tpcn2 knockout mice, which showed normal
      responses to other Ca2+-mobilizing signals. In HEK293 cells stably overexpressing
      human TPC2, shRNA-mediated knockdown of mTOR blocked rapamycin- and NAADP-evoked
      Ca2+ signals. Confocal imaging of a genetically encoded Ca2+ indicator fused to
      TPC2 demonstrated that rapamycin-evoked Ca2+ signals localized to lysosomes and
      were in close proximity to TPC2. Therefore, inactivation of mTOR may activate
      TPC2 and consequently lysosomal Ca2+ release.

PMID- 29636393
TI  - Active Braking of Whole-Arm Reaching Movements Provides Single-Trial
      Neuromuscular Measures of Movement Cancellation.
AB  - Movement inhibition is an aspect of executive control that can be studied using
      the countermanding paradigm, wherein subjects try to cancel an impending movement
      following presentation of a stop signal. This paradigm permits estimation of the
      stop-signal reaction time or the time needed to respond to the stop signal.
      Numerous countermanding studies have examined fast, ballistic movements, such as
      saccades, even though many movements in daily life are not ballistic and can be
      stopped at any point during their trajectory. A benefit of studying the control
      of nonballistic movements is that antagonist muscle recruitment, which serves to
      actively brake a movement, presumably arises in response to the stop signal.
      Here, nine human participants (2 female) performed a center-out whole-arm
      reaching task with a countermanding component, while we recorded the activity of
      upper-limb muscles contributing to movement generation and braking. The data show
      a clear response on antagonist muscles to a stop signal, even for movements that
      have barely begun. As predicted, the timing of such antagonist recruitment
      relative to the stop signal covaried with conventional estimates of the stop
      signal reaction time, both within and across subjects. The timing of antagonist
      muscle recruitment also attested to a rapid reprioritization of movement
      inhibition, with antagonist latencies decreasing across sequences consisting of
      repeated stop trials; such reprioritization also scaled with error magnitude. We
      conclude that antagonist muscle recruitment arises as a manifestation of a
      stopping process, providing a novel, accessible, and within-trial measure of the
      stop-signal reaction time.SIGNIFICANCE STATEMENT The countermanding or stop
      signal paradigm permits estimation of how quickly subjects cancel an impending
      movement. Traditionally, this paradigm has been studied using simple movements,
      such as saccadic eye movements or button presses. Here, by measuring upper limb
      muscle activity while human subjects countermand whole-arm reaching movements, we
      show that movement cancellation often involves prominent recruitment of
      antagonist muscles that serves to actively brake the movement, even on movements
      that have barely begun. The timing of antagonist muscle recruitment correlates
      with traditional estimates of movement cancellation. Because they can be detected
      on a single-trial basis, muscle-based measures may provide a new way of
      characterizing movement cancellation at an unprecedented within-trial resolution.

PMID- 29636392
TI  - Restoration of Kv7 Channel-Mediated Inhibition Reduces Cued-Reinstatement of
      Cocaine Seeking.
AB  - Cocaine addicts display increased sensitivity to drug-associated cues, due in
      part to changes in the prelimbic prefrontal cortex (PL-PFC). The cellular
      mechanisms underlying cue-induced reinstatement of cocaine seeking remain
      unknown. Reinforcement learning for addictive drugs may produce persistent
      maladaptations in intrinsic excitability within sparse subsets of PFC pyramidal
      neurons. Using a model of relapse in male rats, we sampled >600 neurons to
      examine spike frequency adaptation (SFA) and afterhyperpolarizations (AHPs), two
      systems that attenuate low-frequency inputs to regulate neuronal synchronization.
      We observed that training to self-administer cocaine or nondrug (sucrose)
      reinforcers decreased SFA and AHPs in a subpopulation of PL-PFC neurons. Only
      with cocaine did the resulting hyperexcitability persist through extinction
      training and increase during reinstatement. In neurons with intact SFA, dopamine
      enhanced excitability by inhibiting Kv7 potassium channels that mediate SFA.
      However, dopamine effects were occluded in neurons from cocaine-experienced rats,
      where SFA and AHPs were reduced. Pharmacological stabilization of Kv7 channels
      with retigabine restored SFA and Kv7 channel function in neuroadapted cells. When
      microinjected bilaterally into the PL-PFC 10 min before reinstatement testing,
      retigabine reduced cue-induced reinstatement of cocaine seeking. Last, using cFos
      GFP transgenic rats, we found that the loss of SFA correlated with the expression
      of cFos-GFP following both extinction and re-exposure to drug-associated cues.
      Together, these data suggest that cocaine self-administration desensitizes
      inhibitory Kv7 channels in a subpopulation of PL-PFC neurons. This subpopulation
      of neurons may represent a persistent neural ensemble responsible for driving
      drug seeking in response to cues.SIGNIFICANCE STATEMENT Long after the cessation
      of drug use, cues associated with cocaine still elicit drug-seeking behavior, in
      part by activation of the prelimbic prefrontal cortex (PL-PFC). The underlying
      cellular mechanisms governing these activated neurons remain unclear. Using a rat
      model of relapse to cocaine seeking, we identified a population of PL-PFC neurons
      that become hyperexcitable following chronic cocaine self-administration. These
      neurons show persistent loss of spike frequency adaptation, reduced
      afterhyperpolarizations, decreased sensitivity to dopamine, and reduced Kv7
      channel-mediated inhibition. Stabilization of Kv7 channel function with
      retigabine normalized neuronal excitability, restored Kv7 channel currents, and
      reduced drug-seeking behavior when administered into the PL-PFC before
      reinstatement. These data highlight a persistent adaptation in a subset of PL-PFC
      neurons that may contribute to relapse vulnerability.

PMID- 29636394
TI  - Time Course of Brain Network Reconfiguration Supporting Inhibitory Control.
AB  - Hemodynamic research has recently clarified key nodes and links in brain networks
      implementing inhibitory control. Although fMRI methods are optimized for
      identifying the structure of brain networks, the relatively slow temporal course
      of fMRI limits the ability to characterize network operation. The latter is
      crucial for developing a mechanistic understanding of how brain networks shift
      dynamically to support inhibitory control. To address this critical gap, we
      applied spectrally resolved Granger causality (GC) and random forest machine
      learning tools to human EEG data in two large samples of adults (test sample n =
      96, replication sample n = 237, total N = 333, both sexes) who performed a color
      word Stroop task. Time-frequency analysis confirmed that recruitment of
      inhibitory control accompanied by slower behavioral responses was related to
      changes in theta and alpha/beta power. GC analyses revealed directionally
      asymmetric exchanges within frontal and between frontal and parietal brain areas:
      top-down influence of superior frontal gyrus (SFG) over both dorsal ACC (dACC)
      and inferior frontal gyrus (IFG), dACC control over middle frontal gyrus (MFG),
      and frontal-parietal exchanges (IFG, precuneus, MFG). Predictive analytics
      confirmed a combination of behavioral and brain-derived variables as the best set
      of predictors of inhibitory control demands, with SFG theta bearing higher
      classification importance than dACC theta and posterior beta tracking the onset
      of behavioral response. The present results provide mechanistic insight into the
      biological implementation of a psychological phenomenon: inhibitory control is
      implemented by dynamic routing processes during which the target response is
      upregulated via theta-mediated effective connectivity within key PFC nodes and
      via beta-mediated motor preparation.SIGNIFICANCE STATEMENT Hemodynamic
      neuroimaging research has recently clarified regional structures in brain
      networks supporting inhibitory control. However, due to inherent methodological
      constraints, much of this research has been unable to characterize the temporal
      dynamics of such networks (e.g., direction of information flow between nodes).
      Guided by fMRI research identifying the structure of brain networks supporting
      inhibitory control, results of EEG source analysis in a test sample (n = 96) and
      replication sample (n = 237) using effective connectivity and predictive
      analytics strategies advance a model of inhibitory control by characterizing the
      precise temporal dynamics by which this network operates and exemplify an
      approach by which mechanistic models can be developed for other key psychological
      processes.

PMID- 29636395
TI  - Parietal-Occipital Interactions Underlying Control- and Representation-Related
      Processes in Working Memory for Nonspatial Visual Features.
AB  - Although the manipulation of load is popular in visual working memory research,
      many studies confound general attentional demands with context binding by drawing
      memoranda from the same stimulus category. In this fMRI study of human observers
      (both sexes), we created high- versus low-binding conditions, while holding load
      constant, by comparing trials requiring memory for the direction of motion of one
      random dot kinematogram (RDK; 1M trials) versus for three RDKs (3M), or versus
      one RDK and two color patches (1M2C). Memory precision was highest for 1M trials
      and comparable for 3M and 1M2C trials. And although delay-period activity in
      occipital cortex did not differ between the three conditions, returning to
      baseline for all three, multivariate pattern analysis decoding of a remembered
      RDK from occipital cortex was also highest for 1M trials and comparable for 3M
      and 1M2C trials. Delay-period activity in intraparietal sulcus (IPS), although
      elevated for all three conditions, displayed more sensitivity to demands on
      context binding than to load per se. The 1M-to-3M increase in IPS signal
      predicted the 1M-to-3M declines in both behavioral and neural estimates of
      working memory precision. These effects strengthened along a caudal-to-rostral
      gradient, from IPS0 to IPS5. Context binding-independent load sensitivity was
      observed when analyses were lateralized and extended into PFC, with trend-level
      effects evident in left IPS and strong effects in left lateral PFC. These
      findings illustrate how visual working memory capacity limitations arise from
      multiple factors that each recruit dissociable brain systems.SIGNIFICANCE
      STATEMENT Visual working memory capacity predicts performance on a wide array of
      cognitive and real-world outcomes. At least two theoretically distinct factors
      are proposed to influence visual working memory capacity limitations: an amodal
      attentional resource that must be shared across remembered items; and the demands
      on context binding. We unconfounded these two factors by varying load with items
      drawn from the same stimulus category ("high demands on context binding") versus
      items drawn from different stimulus categories ("low demands on context
      binding"). The results provide evidence for the dissociability, and the neural
      bases, of these two theorized factors, and they specify that the functions of
      intraparietal sulcus may relate more strongly to the control of representations
      than to the general allocation of attention.

PMID- 29636397
TI  - An 18-Year-Old With Acute-on-Chronic Abdominal Pain.
AB  - An 18-year-old woman with a complex past medical history presented with 2 days of
      vomiting and lower abdominal pain. She had been admitted for the majority of the
      previous 5 months for recurrent pancreatitis and had undergone a cholecystectomy.
      Additional symptoms included nausea, anorexia, constipation, and a 40-lb weight
      loss over 4 months. She appeared uncomfortable, and an examination was remarkable
      for tachycardia, hypertension, and diffuse abdominal tenderness to light
      palpation. Her initial laboratory test results revealed mildly elevated liver
      enzymes (aspartate aminotransferase 68 U/L, alanine aminotransferase 80 U/L) and
      a normal lipase. She was admitted for pain control and nutritional support. Over
      the next few days, the lipase increased to 1707 U/L. Despite optimizing her
      management for acute pancreatitis, the patient's symptoms persisted. Further
      history gathering and laboratory testing ultimately revealed her diagnosis. Our
      expert panel reviews her hospital course and elucidates the management of our
      eventual diagnosis.

PMID- 29636398
TI  - Seatbelt use is associated with lower risk of high-grade hepatic injury in motor
      vehicle crashes in a national sample.
AB  - BACKGROUND: Seatbelt use, alone and in conjunction with an airbag, is associated
      with lower risk of mortality, blunt abdominal trauma and kidney injury in motor
      vehicle crashes (MVCs). However, the effect of these protective devices on risk
      of severe liver injury is not well characterised. METHODS: This retrospective
      cohort study included patient admissions with liver injuries from MVCs from the
      National Trauma Data Bank (NTDB), collected from 2010 to 2015 in the USA. We
      examined associations between injury severity and seatbelt use and airbag
      presence individually and in the presence of additive interaction. Secondary
      outcomes were mortality, complications and discharge disposition. RESULTS: We
      analysed 55 543 records from the National Trauma Data Bank. In adjusted analysis,
      seatbelt use alone was protective against severe (AAST VI or above) hepatic
      injury (risk ratio (RR) 0.79, 95% CI 0.75 to 0.84), while airbag presence alone
      was not (RR 1.05, 95% CI 0.8 to 1.12). The joint association of seatbelt use and
      airbag presence with injury severity was greater than seatbelts alone (RR 0.74,
      95% CI 0.70 to 0.79), with 13% of the joint lower risk attributable to
      interaction (95% CI 3% to 24%). The adjusted mortality risk of those without
      protective devices (10.3%, n=2297) was nearly double that of patients who used a
      seatbelt in conjunction with a present airbag (5.3%, n=699, p<0.001).
      CONCLUSIONS: Seatbelts are associated with lower liver injury severity and are
      more protective with airbags present, while airbags without seatbelt use were not
      protective against severe injury among patients with liver injury.

PMID- 29636396
TI  - Electrical Stimulation in Hippocampus and Entorhinal Cortex Impairs Spatial and
      Temporal Memory.
AB  - The medial temporal lobe (MTL) is widely implicated in supporting episodic memory
      and navigation, but its precise functional role in organizing memory across time
      and space remains elusive. Here we examine the specific cognitive processes
      implemented by MTL structures (hippocampus and entorhinal cortex) to organize
      memory by using electrical brain stimulation, leveraging its ability to establish
      causal links between brain regions and features of behavior. We studied
      neurosurgical patients of both sexes who performed spatial-navigation and verbal
      episodic memory tasks while brain stimulation was applied in various regions
      during learning. During the verbal memory task, stimulation in the MTL disrupted
      the temporal organization of encoded memories such that items learned with
      stimulation tended to be recalled in a more randomized order. During the spatial
      task, MTL stimulation impaired subjects' abilities to remember items located far
      away from boundaries. These stimulation effects were specific to the MTL. Our
      findings thus provide the first causal demonstration in humans of the specific
      memory processes that are performed by the MTL to encode when and where events
      occurred.SIGNIFICANCE STATEMENT Numerous studies have implicated the medial
      temporal lobe (MTL) in encoding spatial and temporal memories, but they have not
      been able to causally demonstrate the nature of the cognitive processes by which
      this occurs in real-time. Electrical brain stimulation is able to demonstrate
      causal links between a brain region and a given function with high temporal
      precision. By examining behavior in a memory task as subjects received MTL
      stimulation, we provide the first causal evidence demonstrating the role of the
      MTL in organizing the spatial and temporal aspects of episodic memory.

PMID- 29636399
TI  - Changes in non-occupational sedentary behaviours across the retirement
      transition: the Finnish Retirement and Aging (FIREA) study.
AB  - BACKGROUND: Retirement is a major life transition which may influence health
      behaviours and time use. Little is known about how sedentary behaviour changes as
      a result of increased time availability after retirement. The aim of this study
      was to examine changes in non-occupational sedentary behaviours across the
      retirement transition. In addition, we examined which preretirement
      characteristics were associated with these changes. METHODS: The study population
      consisted of 2011 participants from the Finnish Retirement and Aging Study.
      Repeated postal survey including questions on sedentary behaviour domains
      (television viewing, computer use at home, sitting in a vehicle and other
      sitting) were conducted once a year across the retirement transition, covering on
      average 3.4 study waves. Linear regression with generalised estimating equations
      was used for the analyses. RESULTS: Total sedentary time increased by 73 (95% CI
      66 to 80) min/day during the retirement transition. Of the domain-specific
      sedentary behaviours, television viewing time increased by 28 (95% CI 25 to 32)
      min/day, computer use at home by 19 (95% CI 17 to 22) min/day and other sitting
      time by 37 (95% CI 33 to 41) min/day, while time sitting in a vehicle decreased
      by 6 (95% CI 4 to 9) min/day. Highest increase in total sedentary time was among
      women and persons who had high occupational sitting time, low physical activity
      level, sleep difficulties, mental disorders or poor health before retirement (all
      p values for interaction <0.03). CONCLUSION: Total and domain-specific sedentary
      time, except sitting in a vehicle, increased during the retirement transition.

PMID- 29636400
TI  - Standardisation of laboratories engaged in lipid analyses of population health
      examination surveys.
AB  - BACKGROUND: Reliable data on clinical biomarkers are necessary in order to assess
      the health risks of populations and especially in assessing long-term trends
      related to disease incidence. METHODS: Ten European laboratories participated in
      a two-phase quality control exercise of total cholesterol (TC) and high-density
      lipoprotein-cholesterol (HDL-C) analysis. The European Health Examination Survey
      Reference Laboratory prepared plasma batches for analysis, and provided target
      values for them. Two criteria were set for the precision and the systematic error
      (bias). Three plasma samples were analysed in duplicate on separate days (n=12).
      RESULTS: In Round 1, all laboratories met the acceptable criterion (3%) for
      precision of TC. The mean bias of all laboratories was 0.99% (95% CI 0.03% to
      1.95%). Six laboratories measured samples from Round 2. Five laboratories met the
      goal criterion of 3%; one failed to meet the acceptable criterion of 5%. The mean
      bias for HDL-C of the three batches of six laboratories was within goal limits
      (+/-5% from target) and that of all 10 within acceptable (+/-10%). The mean bias
      of all laboratories was 1.1% (95% CI -0.18 to 2.32). In Round 2 four laboratories
      met the goal criterion and one the acceptable criterion. CONCLUSION: The quality
      control exercise demonstrated that although the majority of the laboratories met
      the strict criteria for systematic error for TC and HDL-C, standardisation of
      methods is still needed to improve the accuracy of biomarker measurements of
      laboratories engaged in population health surveys. A protocol is recommended for
      obtaining reliable and comparable biomarker data between countries.

PMID- 29636401
TI  - Clinical and epidemiological variability in severe sepsis: an ecological study.
AB  - BACKGROUND: To assess clinical and epidemiological trends of severe sepsis.
      METHODS: Ecological study of patients presenting to the emergency department with
      severe sepsis or septic shock between 2005 and 2013. Patients were identified
      using the state-wide hospital administrative database. Key outcomes included
      incidence rates (IRs) and mortality rates (per 1000 population) by age and
      medically underserved areas (MUAs), sepsis case fatality rate (deaths per 100
      sepsis cases), and proportions of transfer and comorbidities. RESULTS: There were
      154 019 sepsis cases identified. In 2005, 85+ yo in non-MUAs had a 44% increase
      in IR compared with those in MUAs, and this difference rose to 74% by 2013.
      Mortality rates were 1.6 (95% CI 1.3 to 1.8) times greater among 85+ yo in non
      MUAs. Mortality rates increased by 1.8% annually, while the sepsis case fatality
      rate decreased by 7.7%. The proportion of transfer among sepsis cases decreased
      by 2.1% per year (3.8% in non-MUAs, 0.7% in MUAs). CONCLUSIONS: Sepsis incidence
      varies geographically, and access to healthcare is one proposed mechanism that
      may explain heterogeneity. Over time, we may be capturing higher acuity sepsis
      cases with better recognition and management, as well as observing differential
      diagnostic coding documentation by location.

PMID- 29636402
TI  - Ventricular arrhythmia burden after transcatheter versus surgical pulmonary valve
      replacement.
AB  - OBJECTIVE: Comparative ventricular arrhythmia (VA) outcomes following
      transcatheter (TC-PVR) or surgical pulmonary valve replacement (S-PVR) have not
      been evaluated. We sought to compare differences in VAs among patients with
      congenital heart disease (CHD) following TC-PVR or S-PVR. METHODS: Patients with
      repaired CHD who underwent TC-PVR or S-PVR at the UCLA Medical Center from 2010
      to 2016 were analysed retrospectively. Patients who underwent hybrid TC-PVR or
      had a diagnosis of congenitally corrected transposition of the great arteries
      were excluded. Patients were screened for a composite of non-intraoperative VA
      (the primary outcome variable), defined as symptomatic/recurrent non-sustained
      ventricular tachycardia (VT) requiring therapy, sustained VT or ventricular
      fibrillation. VA epochs were classified as 0-1 month (short-term), 1-12 months
      (mid-term) and >=1 year (late-term). RESULTS: Three hundred and two patients (TC
      PVR, n=172 and S-PVR, n=130) were included. TC-PVR relative to S-PVR was
      associated with fewer clinically significant VAs in the first 30 days after valve
      implant (adjusted HR 0.20, p=0.002), but similar mid-term and late-term risks
      (adjusted HR 0.72, p=0.62 and adjusted HR 0.47, p=0.26, respectively). In
      propensity-adjusted models, S-PVR, patient age at PVR and native right
      ventricular outflow tract (RVOT) (vs bioprosthetic/conduit outflow tract) were
      independent predictors of early VA after pulmonary valve implantation (p<0.05 for
      all). CONCLUSION: Compared with S-PVR, TC-PVR was associated with reduced short
      term but comparable mid-term and late-term VA burdens. Risk factors for VA after
      PVR included a surgical approach, valve implantation into a native RVOT and older
      age at PVR.

PMID- 29636403
TI  - New interventions to treat chronic thromboembolic pulmonary hypertension.
AB  - Chronic thromboembolic pulmonary hypertension (CTEPH) can be defined as a type of
      precapillary pulmonary hypertension (PH) resulting from incomplete resolution of
      pulmonary embolism. Symptoms are exertional breathlessness and most patients come
      to a cardiologist's attention with a dilated right heart on echocardiography.
      Patients with suspected CTEPH should be referred for evaluation to a PH
      specialist centre to confirm the diagnosis. There are now three treatment options
      available, dependent on the anatomical level of the obstruction: pulmonary
      endarterectomy surgery, balloon pulmonary angioplasty and pulmonary arterial
      hypertension (PAH)-targeted drugs. All reduce pulmonary artery pressure and
      vascular resistance. Current guidelines recommend surgery as the definitive
      treatment in technically operable patients. The operation involves deep
      hypothermic circulatory arrest, but the in-hospital mortality is <5% and the 3
      year survival is 90%. Large case series have demonstrated dramatic improvement in
      haemodynamic parameters with significant symptomatic and prognostic benefits.
      Balloon pulmonary angioplasty is the newest treatment that has been refined by
      Japanese cardiologists over the last 5 years. This technique is designed to
      target more distal subsegmental lesions in inoperable patients and in experienced
      centres has been shown to deliver equivalent haemodynamic improvement to surgery
      with low complication rates, but longer term outcome is still under evaluation. A
      recent randomised controlled trial has demonstrated a reduction in vascular
      resistance and increase in walk test distance with the PAH-targeted drug
      Riociguat in patients with inoperable CTEPH, and this drug is now licensed for
      these patients. It is likely that some patients will benefit from combinations of
      treatments.

PMID- 29636404
TI  - Development of ICSI.
AB  - The first conception outside of the human body that led to the birth of Louise
      Brown was a tremendous accomplishment, which opened the door to the utilization
      of assisted reproductive techniques globally. This brought the understanding that
      accomplishing life in a dish required several steps, the most obvious being the
      timing and characteristics of fertilization. It soon became obvious in the 1980s
      that the most disappointing phenomenon was unexpected and complete fertilization
      failure. Among the approaches that were attempted to treat male factor
      infertility, ICSI surfaced as the technique that brought the ratio of the gametes
      to 1:1 and was also able to grant consistent fertilization and a higher pregnancy
      rate. ICSI has now been implemented for a quarter of a century, proving itself as
      the ultimate technique utilizing ejaculated spermatozoa independent of the semen
      parameters and is the sole insemination method to be used with surgically
      retrieved spermatozoa. There are currently various indications for ICSI that are
      widely adopted, rendering it the most popular insemination method worldwide. The
      reliability of ICSI ensures its employment in upcoming techniques involving in
      vitro spermatogenesis and neogametogenesis.

PMID- 29636405
TI  - 40 years of bovine IVF in the new genomic selection context.
AB  - The development of a complex technology such as in vitro fertilization (IVF)
      requires years of experimentation, sometimes comparing several species to learn
      how to create the right in vitro environment for oocytes, spermatozoa and early
      embryos. At the same time, individual species characteristics such as gamete
      physiology and gamete interaction are recently evolved traits and must be
      analysed within the context of each species. In the last 40 years since the birth
      of Louise Brown, IVF techniques progressed and are now used in multiple domestic
      and non-domestic animal species around the world. This does not mean that the
      technology is completely matured or satisfactory; a number of problems remain to
      be solved and several procedures still need to be optimized. The development of
      IVF in cattle is particularly interesting since agriculture practices permitted
      the commercial development of the procedure and it is now used at a scale
      comparable to human IVF (millions of newborns). The genomic selection of young
      animals or even embryos combined with sexing and freezing technologies is driving
      a new era of IVF in the dairy sector. The time has come for a retrospective
      analysis of the success and pitfalls of the last 40 years of bovine IVF and for
      the description of the challenges to overcome in the years to come.

PMID- 29636406
TI  - The impact of infertility diagnosis on embryo-endometrial dialogue.
AB  - Initial stages of implantation involve bi-directional molecular crosstalk between
      the blastocyst and endometrium. This study investigated an association between
      infertility etiologies, specifically advanced maternal age (AMA) and
      endometriosis, on the embryo-endometrial molecular dialogue prior to
      implantation. Co-culture experiments were performed with endometrial epithelial
      cells (EEC) and cryopreserved day 5 blastocysts (n = 41 >= Grade 3BB) donated
      from patients presenting with AMA or endometriosis, compared to fertile donor
      oocyte controls. Extracellular vesicles isolated from co-culture supernatant were
      analyzed for miRNA expression and revealed significant alterations correlating to
      AMA or endometriosis. Specifically, AMA resulted in 16 miRNAs with increased
      expression (P <= 0.05) and strong evidence for negative regulation toward 206
      target genes. VEGFA, a known activator of cell adhesion, displayed decreased
      expression (P <= 0.05), validating negative regulation by 4 of these increased
      miRNAs: miR-126; 150; 29a; 29b (P <= 0.05). In endometriosis patients, a total of
      10 significantly altered miRNAs displayed increased expression compared to
      controls (miR-7b; 9; 24; 34b; 106a; 191; 200b; 200c; 342-3p; 484) (P <= 0.05),
      targeting 1014 strong evidence-based genes. Three target genes of miR-106a
      (CDKN1A, E2F1 and RUNX1) were independently validated. Functional annotation
      analysis of miRNA-target genes revealed enriched pathways for both infertility
      etiologies, including disrupted cell cycle regulation and proliferation (P <=
      0.05). These extracellular vesicle-bound secreted miRNAs are key transcriptional
      regulators in embryo-endometrial dialogue and may be prospective biomarkers of
      implantation success. One of the limitations of this study is that it was a
      stimulated, in vitro model and therefore may not accurately reflect the in-vivo
      environment.

PMID- 29636407
TI  - Radiation-induced ovarian follicle loss occurs without overt stromal changes.
AB  - Radiation damage due to total body irradiation (TBI) or targeted abdominal
      radiation can deplete ovarian follicles and accelerate reproductive aging. We
      characterized a mouse model of low-dose TBI to investigate how radiation affects
      the follicular and stromal compartments of the ovary. A single TBI dose of either
      0.1 Gy or 1 Gy (Cesium-137 gamma) was delivered to reproductively adult CD1
      female mice, and sham-treated mice served as controls. Mice were euthanized
      either 2 weeks or 5 weeks post exposure, and ovarian tissue was harvested. To
      assess the ovarian reserve, we classified and counted the number of
      morphologically normal follicles in ovarian histologic sections for all
      experimental cohorts using an objective method based on immunohistochemistry for
      an oocyte-specific protein (MSY2). 0.1 Gy did not affect that total number of
      ovarian follicles, whereas 1 Gy resulted in a dramatic loss. At two weeks, there
      was a significant reduction in all preantral follicles, but early antral and
      antral follicles were still present. By five weeks, there was complete depletion
      of all follicle classes. We examined stromal quality using histologic stains to
      visualize ovarian architecture and fibrosis and by immunohistochemistry and
      quantitative microscopy to assess cell proliferation, cell death and vasculature.
      There were no differences in the ovarian stroma across cohorts with respect to
      these markers, indicating that this compartment is more radio-resistant relative
      to the germ cells. These findings have implications for reproductive health and
      the field of fertility preservation because the radiation doses we examined mimic
      scatter doses experienced in typical therapeutic regimens.

PMID- 29636408
TI  - Cues for cavity nesters: investigating relevant zeitgebers for emerging
      leafcutting bees, Megachile rotundata.
AB  - Photoperiod is considered the universal zeitgeber, regulating physiological
      processes in numerous animals. However, for animals in light-restricted habitats
      (e.g. burrows or cavities), thermoperiod may be a more important cue. Our study
      tested this hypothesis in the alfalfa leafcutting bee, Megachile rotundata, which
      nests in cavities and undergoes development within a brood cell. We assessed the
      role of environmental cues (thermoperiod and photoperiod) on the process of adult
      emergence by examining: (1) whether those cues direct circadian rhythms, (2)
      which cue is more dominant and (3) how sensitive developing bees and emergence
      ready adults are to cues. Although we found that 20% of light penetrates the
      brood cell, and bees respond to photoperiod by synchronizing emergence,
      thermoperiod is the dominant cue. When presented with a conflicting zeitgeber,
      bees entrained to the thermophase instead of the photophase. When temperature
      cues were removed, we observed free-running of emergence, indicating that
      underlying circadian mechanisms can be synchronized by daily fluctuations in
      temperature. We also found that emerging bees were highly sensitive to even small
      increases in temperature, entraining to a ramp speed of 0.33 degrees C h-1 The
      response and sensitivity to temperature cues suggest that M. rotundata evolved a
      temperature-mediated clock to time emergence from light-restricted cavities.

PMID- 29636410
TI  - Kinematics of burrowing by peristalsis in granular sands.
AB  - Peristaltic burrowing in muds applies normal forces to burrow walls, which extend
      by fracture, but the kinematics and mechanics of peristaltic burrowing in sands
      has not been explored. The opheliid polychaete Thoracophelia mucronata uses
      direct peristalsis to burrow in beach sands, with kinematics consistent with the
      'dual anchor system' of burrowing described for diverse organisms. In addition to
      expansions associated with a constrictive direct peristaltic wave, worms
      alternately expand the head region, which is separated by septa from the open
      body cavity, and expansible lateral ridges that protrude from the 10th setiger.
      Tracking of chaetae with fluorescent dye showed that the body wall advances while
      segments are thin, then stationary segments expand, applying normal forces to
      burrow walls. These normal forces likely compact burrow walls and serve as
      anchors. Perhaps more importantly, peristaltic movements minimize friction with
      the burrow wall, which would expand dilatant sands. Considerable slipping of
      worms burrowing in a lower-density sand analog suggests that this dual-anchor
      peristaltic burrowing may be limited to a narrow range of mechanical properties
      of substrata, consistent with the limited habitat of T. mucronata in a narrow
      swash zone on dissipative beaches.

PMID- 29636409
TI  - Telomere elongation during early development is independent of environmental
      temperatures in Atlantic salmon.
AB  - There is increasing evidence from endothermic vertebrates that telomeres, which
      cap the ends of chromosomes and play an important role in chromosome protection,
      decline in length during postnatal life and are a useful indicator of
      physiological state and expected lifespan. However, much less is currently known
      about telomere dynamics in ectothermic vertebrates, which are likely to differ
      from that of endotherms, at least in part due to the sensitivity of ectotherm
      physiology to environmental temperature. We report here on an experiment in which
      Atlantic salmon (Salmo salar) were reared through the embryonic and larval stages
      of development, and under differing temperatures, in order to examine the effects
      of environmental temperature during early life on telomere dynamics, oxidative
      DNA damage and cellular proliferation. Telomere length significantly increased
      between the embryonic and larval stages of development. Contrary to our
      expectations, variation in telomere length at the end of the larval stage was
      unrelated to either cell proliferation rate or the relative level of oxidative
      DNA damage, and did not vary between the temperature treatments. This study
      suggests that salmon are able to restore the length of their telomeres during
      early development, which may possibly help to buffer potentially harmful
      environmental effects experienced in early life.

PMID- 29636411
TI  - Digestive and locomotor capacity show opposing responses to changing food
      availability in an ambush predatory fish.
AB  - Metabolic rates vary widely within species, but little is known about how
      variation in the 'floor' [i.e. standard metabolic rate (SMR) in ectotherms] and
      'ceiling' [maximum metabolic rate (MMR)] for an individual's aerobic scope (AS)
      are linked with digestive and locomotor function. Any links among metabolic
      traits and aspects of physiological performance may also be modulated by
      fluctuations in food availability. This study followed changes in SMR, MMR, and
      digestive and locomotor capacity in southern catfish (Silurus meridionalis)
      throughout 15 days of food deprivation and 15 days of refeeding. Individuals
      downregulated SMR during food deprivation and showed only a 10% body mass
      decrease during this time. Whereas critical swim speed (Ucrit) was robust to food
      deprivation, digestive function decreased after fasting with a reduced peak
      oxygen uptake during specific dynamic action (SDA) and prolonged SDA duration.
      During refeeding, individuals displayed rapid growth and digestive function
      recovered to pre-fasting levels. However, refed fish showed a lower Ucrit than
      would be expected for their increased body length and in comparison to measures
      at the start of the study. Reduced swimming ability may be a consequence of
      compensatory growth: growth rate was negatively correlated with changes in Ucrit
      during refeeding. Southern catfish downregulate digestive function to reduce
      energy expenditure during food deprivation, but regain digestive capacity during
      refeeding, potentially at the cost of decreased swimming performance. The
      plasticity of maintenance requirements suggests that SMR is a key fitness trait
      for in this ambush predator. Shifts in trait correlations with food availability
      suggest that the potential for correlated selection may depend on context.

PMID- 29636412
TI  - Structural modeling of an outer membrane electron conduit from a metal-reducing
      bacterium suggests electron transfer via periplasmic redox partners.
AB  - Many subsurface microorganisms couple their metabolism to the reduction or
      oxidation of extracellular substrates. For example, anaerobic mineral-respiring
      bacteria can use external metal oxides as terminal electron acceptors during
      respiration. Porin-cytochrome complexes facilitate the movement of electrons
      generated through intracellular catabolic processes across the bacterial outer
      membrane to these terminal electron acceptors. In the mineral-reducing model
      bacterium Shewanella oneidensis MR-1, this complex is composed of two decaheme
      cytochromes (MtrA and MtrC) and an outer-membrane beta-barrel (MtrB). However,
      the structures and mechanisms by which porin-cytochrome complexes transfer
      electrons are unknown. Here, we used small-angle neutron scattering (SANS) to
      study the molecular structure of the transmembrane complexes MtrAB and MtrCAB. Ab
      initio modeling of the scattering data yielded a molecular envelope with
      dimensions of ~105 * 60 * 35 A for MtrAB and ~170 * 60 * 45 A for MtrCAB. The
      shapes of these molecular envelopes suggested that MtrC interacts with the
      surface of MtrAB, extending ~70 A from the membrane surface and allowing the
      terminal hemes to interact with both MtrAB and an extracellular acceptor. The
      data also reveal that MtrA fully extends through the length of MtrB, with ~30 A
      being exposed into the periplasm. Proteoliposome models containing membrane
      associated MtrCAB and internalized small tetraheme cytochrome (STC) indicate that
      MtrCAB could reduce Fe(III) citrate with STC as an electron donor, disclosing a
      direct interaction between MtrCAB and STC. Taken together, both structural and
      proteoliposome experiments support porin-cytochrome-mediated electron transfer
      via periplasmic cytochromes such as STC.

PMID- 29636413
TI  - Dimerization of the cellular prion protein inhibits propagation of scrapie
      prions.
AB  - A central step in the pathogenesis of prion diseases is the conformational
      transition of the cellular prion protein (PrPC) into the scrapie isoform, denoted
      PrPSc Studies in transgenic mice have indicated that this conversion requires a
      direct interaction between PrPC and PrPSc; however, insights into the underlying
      mechanisms are still missing. Interestingly, only a subfraction of PrPC is
      converted in scrapie-infected cells, suggesting that not all PrPC species are
      suitable substrates for the conversion. On the basis of the observation that PrPC
      can form homodimers under physiological conditions with the internal hydrophobic
      domain (HD) serving as a putative dimerization domain, we wondered whether PrP
      dimerization is involved in the formation of neurotoxic and/or infectious PrP
      conformers. Here, we analyzed the possible impact on dimerization of pathogenic
      mutations in the HD that induce a spontaneous neurodegenerative disease in
      transgenic mice. Similarly to wildtype (WT) PrPC, the neurotoxic variant PrP(AV3)
      formed homodimers as well as heterodimers with WTPrPC Notably, forced PrP
      dimerization via an intermolecular disulfide bond did not interfere with its
      maturation and intracellular trafficking. Covalently linked PrP dimers were
      complex glycosylated, GPI-anchored, and sorted to the outer leaflet of the plasma
      membrane. However, forced PrPC dimerization completely blocked its conversion
      into PrPSc in chronically scrapie-infected mouse neuroblastoma cells. Moreover,
      PrPC dimers had a dominant-negative inhibition effect on the conversion of
      monomeric PrPC Our findings suggest that PrPC monomers are the major substrates
      for PrPSc propagation and that it may be possible to halt prion formation by
      stabilizing PrPC dimers.

PMID- 29636414
TI  - Annexins A2 and A6 interact with the extreme N terminus of tau and thereby
      contribute to tau's axonal localization.
AB  - During neuronal development, the microtubule-associated protein tau becomes
      enriched in the axon, where it remains concentrated in the healthy brain. In
      tauopathies such as Alzheimer's disease, tau redistributes from the axon to the
      somatodendritic compartment. However, the cellular mechanism that regulates tau's
      localization remains unclear. We report here that tau interacts with the Ca2+
      regulated plasma membrane-binding protein annexin A2 (AnxA2) via tau's extreme N
      terminus encoded by the first exon (E1). Bioinformatics analysis identified two
      conserved eight-amino-acids-long motifs within E1 in mammals. Using a
      heterologous yeast system, we found that disease-related mutations and
      pseudophosphorylation of Tyr-18, located within E1 but outside of the two
      conserved regions, do not influence tau's interaction with AnxA2. We further
      observed that tau interacts with the core domain of AnxA2 in a Ca2+-induced open
      conformation and interacts also with AnxA6. Moreover, lack of E1 moderately
      increased tau's association rate to microtubules, consistent with the supposition
      that the presence of the tau-annexin interaction reduces the availability of tau
      to interact with microtubules. Of note, intracellular competition through
      overexpression of E1-containing constructs reduced tau's axonal enrichment in
      primary neurons. Our results suggest that the E1-mediated tau-annexin interaction
      contributes to the enrichment of tau in the axon and is involved in its
      redistribution in pathological conditions.

PMID- 29636415
TI  - Characterization of AJH-836, a diacylglycerol-lactone with selectivity for novel
      PKC isozymes.
AB  - Diacylglycerol (DAG) is a key lipid second messenger downstream of cellular
      receptors that binds to the C1 domain in many regulatory proteins. Protein kinase
      C (PKC) isoforms constitute the most prominent family of signaling proteins with
      DAG-responsive C1 domains, but six other families of proteins, including the
      chimaerins, Ras-guanyl nucleotide-releasing proteins (RasGRPs), and Munc13
      isoforms, also play important roles. Their significant involvement in cancer,
      immunology, and neurobiology has driven intense interest in the C1 domain as a
      therapeutic target. As with other classes of targets, however, a key issue is the
      establishment of selectivity. Here, using [3H]phorbol 12,13-dibutyrate ([3H]PDBu)
      competition binding assays, we found that a synthetic DAG-lactone, AJH-836,
      preferentially binds to the novel PKC isoforms PKCdelta and PKCepsilon relative
      to classical PKCalpha and PKCbetaII. Assessment of intracellular translocation, a
      hallmark for PKC activation, revealed that AJH-836 treatment stimulated a
      striking preferential redistribution of PKCepsilon to the plasma membrane
      relative to PKCalpha. Moreover, unlike with the prototypical phorbol ester
      phorbol 12-myristate 13-acetate (PMA), prolonged exposure of cells to AJH-836
      selectively down-regulated PKCdelta and PKCepsilon without affecting PKCalpha
      expression levels. Biologically, AJH-836 induced major changes in cytoskeletal
      reorganization in lung cancer cells, as determined by the formation of membrane
      ruffles, via activation of novel PKCs. We conclude that AJH-836 represents a C1
      domain ligand with PKC-activating properties distinct from those of natural DAGs
      and phorbol esters. Our study supports the feasibility of generating selective C1
      domain ligands that promote novel biological response patterns.

PMID- 29636416
TI  - TLR4, TRIF, and MyD88 are essential for myelopoiesis and CD11c+ adipose tissue
      macrophage production in obese mice.
AB  - Obesity-induced chronic inflammation is associated with metabolic disease.
      Results from mouse models utilizing a high-fat diet (HFD) have indicated that an
      increase in activated macrophages, including CD11c+ adipose tissue macrophages
      (ATMs), contributes to insulin resistance. Obesity primes myeloid cell production
      from hematopoietic stem cells (HSCs) and Toll-like receptor 4 (TLR4), and the
      downstream TIR domain-containing adapter protein-inducing interferon-beta (TRIF)-
      and MyD88-mediated pathways regulate production of similar myeloid cells after
      lipopolysaccharide stimulation. However, the role of these pathways in HFD
      induced myelopoiesis is unknown. We hypothesized that saturated fatty acids and
      HFD alter myelopoiesis by activating TLR4 pathways in HSCs, differentially
      producing pro-inflammatory CD11c+ myeloid cells that contribute to obesity
      induced metabolic disease. Results from reciprocal bone marrow transplants (BMTs)
      with Tlr4-/- and WT mice indicated that TLR4 is required for HFD-induced
      myelopoiesis and production of CD11c+ ATMs. Experiments with homozygous knockouts
      of Irakm (encoding a suppressor of MyD88 inactivation) and Trif in competitive
      BMTs revealed that MyD88 is required for HFD expansion of granulocyte macrophage
      progenitors and that Trif is required for pregranulocyte macrophage progenitor
      expansion. A comparison of WT, Tlr4-/-, Myd88-/-, and Trif-/- mice on HFD
      demonstrated that TLR4 plays a role in the production of CD11c+ ATMs, and both
      Myd88-/- and Trif-/- mice produced fewer ATMs than WT mice. Moreover, HFD-induced
      TLR4 activation inhibited macrophage proliferation, leading to greater
      accumulation of recruited CD11c+ ATMs. Our results indicate that HFD potentiates
      TLR4 and both its MyD88- and TRIF-mediated downstream pathways within progenitors
      and adipose tissue and leads to macrophage polarization.

PMID- 29636417
TI  - Crystal structure and mechanism of human carboxypeptidase O: Insights into its
      specific activity for acidic residues.
AB  - Human metallocarboxypeptidase O (hCPO) is a recently discovered digestive enzyme
      localized to the apical membrane of intestinal epithelial cells. Unlike
      pancreatic metallocarboxypeptidases, hCPO is glycosylated and produced as an
      active enzyme with distinctive substrate specificity toward C-terminal (C-t)
      acidic residues. Here we present the crystal structure of hCPO at 1.85-A
      resolution, both alone and in complex with a carboxypeptidase inhibitor (NvCI)
      from the marine snail Nerita versicolor The structure provides detailed
      information regarding determinants of enzyme specificity, in particular Arg275,
      placed at the bottom of the substrate-binding pocket. This residue, located at
      "canonical" position 255, where it is Ile in human pancreatic carboxypeptidases
      A1 (hCPA1) and A2 (hCPA2) and Asp in B (hCPB), plays a dominant role in
      determining the preference of hCPO for acidic C-t residues. Site-directed
      mutagenesis to Asp and Ala changes the specificity to C-t basic and hydrophobic
      residues, respectively. The single-site mutants thus faithfully mimic the
      enzymatic properties of CPB and CPA, respectively. hCPO also shows a preference
      for Glu over Asp, probably as a consequence of a tighter fitting of the Glu side
      chain in its S1' substrate-binding pocket. This unique preference of hCPO,
      together with hCPA1, hCPA2, and hCPB, completes the array of C-t cleavages
      enabling the digestion of the dietary proteins within the intestine. Finally, in
      addition to activity toward small synthetic substrates and peptides, hCPO can
      also trim C-t extensions of proteins, such as epidermal growth factor, suggesting
      a role in the maturation and degradation of growth factors and bioactive
      peptides.

PMID- 29636418
TI  - Spider toxin inhibits gating pore currents underlying periodic paralysis.
AB  - Gating pore currents through the voltage-sensing domains (VSDs) of the skeletal
      muscle voltage-gated sodium channel NaV1.4 underlie hypokalemic periodic
      paralysis (HypoPP) type 2. Gating modifier toxins target ion channels by
      modifying the function of the VSDs. We tested the hypothesis that these toxins
      could function as blockers of the pathogenic gating pore currents. We report that
      a crab spider toxin Hm-3 from Heriaeus melloteei can inhibit gating pore currents
      due to mutations affecting the second arginine residue in the S4 helix of VSD-I
      that we have found in patients with HypoPP and describe here. NMR studies show
      that Hm-3 partitions into micelles through a hydrophobic cluster formed by
      aromatic residues and reveal complex formation with VSD-I through electrostatic
      and hydrophobic interactions with the S3b helix and the S3-S4 extracellular loop.
      Our data identify VSD-I as a specific binding site for neurotoxins on sodium
      channels. Gating modifier toxins may constitute useful hits for the treatment of
      HypoPP.

PMID- 29636420
TI  - Experimental demonstration of an isotope-sensitive warhead verification technique
      using nuclear resonance fluorescence.
AB  - Future nuclear arms reduction efforts will require technologies to verify that
      warheads slated for dismantlement are authentic without revealing any sensitive
      weapons design information to international inspectors. Despite several decades
      of research, no technology has met these requirements simultaneously. Recent work
      by Kemp et al. [Kemp RS, Danagoulian A, Macdonald RR, Vavrek JR (2016) Proc Natl
      Acad Sci USA 113:8618-8623] has produced a novel physical cryptographic
      verification protocol that approaches this treaty verification problem by
      exploiting the isotope-specific nature of nuclear resonance fluorescence (NRF)
      measurements to verify the authenticity of a warhead. To protect sensitive
      information, the NRF signal from the warhead is convolved with that of an
      encryption foil that contains key warhead isotopes in amounts unknown to the
      inspector. The convolved spectrum from a candidate warhead is statistically
      compared against that from an authenticated template warhead to determine whether
      the candidate itself is authentic. Here we report on recent proof-of-concept
      warhead verification experiments conducted at the Massachusetts Institute of
      Technology. Using high-purity germanium (HPGe) detectors, we measured NRF spectra
      from the interrogation of proxy "genuine" and "hoax" objects by a 2.52 MeV
      endpoint bremsstrahlung beam. The observed differences in NRF intensities near
      2.2 MeV indicate that the physical cryptographic protocol can distinguish between
      proxy genuine and hoax objects with high confidence in realistic measurement
      times.

PMID- 29636419
TI  - Transcriptome-wide discovery of coding and noncoding RNA-binding proteins.
AB  - Transcriptome-wide identification of RNA-binding proteins (RBPs) is a
      prerequisite for understanding the posttranscriptional gene regulation networks.
      However, proteomic profiling of RBPs has been mostly limited to polyadenylated
      mRNA-binding proteins, leaving RBPs on nonpoly(A) RNAs, including most noncoding
      RNAs (ncRNAs) and pre-mRNAs, largely undiscovered. Here we present a click
      chemistry-assisted RNA interactome capture (CARIC) strategy, which enables
      unbiased identification of RBPs, independent of the polyadenylation state of
      RNAs. CARIC combines metabolic labeling of RNAs with an alkynyl uridine analog
      and in vivo RNA-protein photocross-linking, followed by click reaction with azide
      biotin, affinity enrichment, and proteomic analysis. Applying CARIC, we
      identified 597 RBPs in HeLa cells, including 130 previously unknown RBPs. These
      newly discovered RBPs can likely bind ncRNAs, thus uncovering potential
      involvement of ncRNAs in processes previously unknown to be ncRNA-related, such
      as proteasome function and intermediary metabolism. The CARIC strategy should be
      broadly applicable across various organisms to complete the census of RBPs.

PMID- 29636422
TI  - Beneficial Role of Neutrophils Through Function of Lactoferrin After
      Intracerebral Hemorrhage.
AB  - BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) is a devastating disease
      with a 30-day mortality of ~50%. There are no effective therapies for ICH. ICH
      results in brain damage in 2 major ways: through the mechanical forces of
      extravasated blood and then through toxicity of the intraparenchymal blood
      components including hemoglobin/iron. LTF (lactoferrin) is an iron-binding
      protein, uniquely abundant in polymorphonuclear neutrophils (PMNs). After ICH,
      circulating blood PMNs enter the ICH-afflicted brain where they release LTF. By
      virtue of sequestrating iron, LTF may contribute to hematoma detoxification.
      METHODS: ICH in mice was produced using intrastriatal autologous blood injection.
      PMNs were depleted with intraperitoneal administration of anti-Ly-6G antibody.
      Treatment of mouse brain cell cultures with lysed RBC or iron was used as in
      vitro model of ICH. RESULTS: LTF mRNA was undetectable in the mouse brain, even
      after ICH. Unlike mRNA, LTF protein increased in ICH-affected hemispheres by 6
      hours, peaked at 24 to 72 hours, and remained elevated for at least a week after
      ICH. At the single cell level, LTF was detected in PMNs in the hematoma-affected
      brain at all time points after ICH. We also found elevated LTF in the plasma
      after ICH, with a temporal profile similar to LTF changes in the brain.
      Importantly, mrLTF (recombinant mouse LTF) reduced the cytotoxicity of lysed RBC
      and FeCl3 to brain cells in culture. Ultimately, in an ICH model, systemic
      administration of mrLTF (at 3, 24, and 48 hours after ICH) reduced brain edema
      and ameliorated neurological deficits caused by ICH. mrLTF retained the benefit
      in reducing behavioral deficit even with 24-hour treatment delay. Interestingly,
      systemic depletion of PMNs at 24 hours after ICH worsened neurological deficits,
      suggesting that PMN infiltration into the brain at later stages after ICH could
      be a beneficial response. CONCLUSIONS: LTF delivered to the ICH-affected brain by
      infiltrating PMNs may assist in hematoma detoxification and represent a powerful
      potential target for the treatment of ICH.

PMID- 29636421
TI  - Roles of the CSE1L-mediated nuclear import pathway in epigenetic silencing.
AB  - Epigenetic silencing can be mediated by various mechanisms, and many regulators
      remain to be identified. Here, we report a genome-wide siRNA screening to
      identify regulators essential for maintaining gene repression of a CMV promoter
      silenced by DNA methylation. We identified CSE1L (chromosome segregation 1 like)
      as an essential factor for the silencing of the reporter gene and many endogenous
      methylated genes. CSE1L depletion did not cause DNA demethylation. On the other
      hand, the methylated genes derepressed by CSE1L depletion largely overlapped with
      methylated genes that were also reactivated by treatment with histone deacetylase
      inhibitors (HDACi). Gene silencing defects observed upon CSE1L depletion were
      linked to its nuclear import function for certain protein cargos because
      depletion of other factors involved in the same nuclear import pathway, including
      KPNAs and KPNB1 proteins, displayed similar derepression profiles at the genome
      wide level. Therefore, CSE1L appears to be critical for the nuclear import of
      certain key repressive proteins. Indeed, NOVA1, HDAC1, HDAC2, and HDAC8, genes
      known as silencing factors, became delocalized into cytosol upon CSE1L depletion.
      This study suggests that the cargo specificity of the protein nuclear import
      system may impact the selectivity of gene silencing.

PMID- 29636423
TI  - Impact of Smoking on Clinical Outcome and Recanalization After Intravenous
      Thrombolysis for Stroke: Multicenter Cohort Study.
AB  - BACKGROUND AND PURPOSE: The impact of smoking on prognosis after stroke is
      controversial. We aimed to assess the relationship between smoking status and
      stroke outcome after intravenous thrombolysis in a large cohort study by
      adjusting for potential confounders and incorporating recanalization rates.
      METHODS: In a prospective observational multicenter study, we analyzed baseline
      and outcome data of consecutive patients with acute ischemic stroke treated with
      intravenous thrombolysis. Using uni- and multivariable modeling, we assessed
      whether smoking was associated with favorable outcome (modified Rankin Scale
      score of 0-1) and mortality. In addition, we also measured the occurrence of
      symptomatic intracranial hemorrhage and recanalization of middle cerebral artery.
      Patients reporting active cigarette use were classified as smokers. RESULTS: Of
      1865 patients, 19.8% were smokers (n=369). They were younger (mean 63.5 versus
      71.3 years), less often women (56% versus 72.1%), and suffered less often from
      hypertension (61.3% versus 70.1%) and atrial fibrillation (22.7% versus 35.6%)
      when compared with nonsmokers. Favorable outcome and 3-month mortality were in
      favor of smokers in unadjusted analyses (45.8% versus 39.5% and 9.3% versus
      15.8%, respectively), whereas symptomatic intracranial hemorrhage was comparable
      in both cohorts. Smoking was not associated with clinical outcome and mortality
      after adjusting for confounders (odds ratio, 1.20; 95% confidence interval, 0.91
      1.61; P=0.197 and odds ratio, 1.08; 95% confidence interval, 0.68-1.71; P=0.755,
      respectively). However, smoking still independently predicted recanalization of
      middle cerebral artery in multivariable analyses (odds ratio, 2.68; 95%
      confidence interval, 1.11-6.43; P=0.028). CONCLUSIONS: Our study suggests that
      good outcome in smokers is mainly related to differences in baseline
      characteristics and not to biological effects of smoking. The higher
      recanalization rates in smokers, however, call for further studies.

PMID- 29636425
TI  - Growth Hormone Improves Cognitive Function After Experimental Stroke.
AB  - BACKGROUND AND PURPOSE: Cognitive impairment is a common outcome for stroke
      survivors. Growth hormone (GH) could represent a potential therapeutic option as
      this peptide hormone has been shown to improve cognition in various clinical
      conditions. In this study, we evaluated the effects of peripheral administration
      of GH at 48 hours poststroke for 28 days on cognitive function and the underlying
      mechanisms. METHODS: Experimental stroke was induced by photothrombotic occlusion
      in young adult mice. We assessed the associative memory cognitive domain using
      mouse touchscreen platform for paired-associate learning task. We also evaluated
      neural tissue loss, neurotrophic factors, and markers of neuroplasticity and
      cerebrovascular remodeling using biochemical and histology analyses. RESULTS: Our
      results show that GH-treated stroked mice made a significant improvement on the
      paired-associate learning task relative to non-GH-treated mice at the end of the
      study. Furthermore, we observed reduction of neural tissue loss in GH-treated
      stroked mice. We identified that GH treatment resulted in significantly higher
      levels of neurotrophic factors (IGF-1 [insulin-like growth factor-1] and VEGF
      [vascular endothelial growth factor]) in both the circulatory and peri-infarct
      regions. GH treatment in stroked mice not only promoted protein levels and
      density of presynaptic marker (SYN-1 [synapsin-1]) and marker of myelination (MBP
      [myelin basic protein]) but also increased the density and area coverage of 2
      major vasculature markers (CD31 and collagen-IV), within the peri-infarct region.
      CONCLUSIONS: These findings provide compelling preclinical evidence for the usage
      of GH as a potential therapeutic tool in the recovery phase of patients after
      stroke.

PMID- 29636426
TI  - Opinion: How to achieve better flood-risk governance in the United States.

PMID- 29636424
TI  - Frequency of Patent Foramen Ovale and Migraine in Patients With Cryptogenic
      Stroke.
AB  - BACKGROUND AND PURPOSE: Individuals with migraine are at higher risk for stroke,
      but the mechanism has not been established. On the basis of the association
      between migraine and intracardiac right-to-left shunt, it has been proposed that
      stroke in migraineurs could be caused by a paradoxical embolus passing through a
      patent foramen ovale (PFO) or pulmonary arteriovenous malformation. The aim of
      this study was to determine the prevalence of PFO with right-to-left shunt in
      patients who presented with cryptogenic stroke and had a history of migraine.
      METHODS: Patients between 18 and 60 years old who presented with an ischemic
      stroke were characterized based on ASCOD phenotyping (atherosclerosis; small
      vessel disease; cardiac pathology; other causes; dissection). A migraine
      diagnosis was identified by reviewing physician notes, and frequent aura was
      defined if present in at least 50% of attacks. A PFO with right-to-left shunt
      diagnosis was identified by the presence of a positive bubble contrast study with
      either transcranial Doppler, transthoracic, or transesophageal echocardiography.
      RESULTS: Of the 712 patients who presented with ischemic stroke, 127 (18%) were
      diagnosed as cryptogenic; 68 patients had adequate testing for PFO and a
      documented migraine history. The prevalence of PFO in patients with cryptogenic
      stroke without migraine was elevated (59%) compared with the general population
      (18%). Patients with both cryptogenic stroke and migraine had a higher prevalence
      of PFO (79%). In patients with cryptogenic stroke who had migraine with frequent
      aura, the prevalence of PFO was 93%. Only 5 patients (4%) had a history
      compatible with migrainous infarction. CONCLUSIONS: In patients with cryptogenic
      stroke who have migraine, there is a high prevalence (79%) of PFO with right-to
      left shunt. The timing of the stroke in migraineurs is usually not related to a
      migraine attack. These observations are consistent with the hypothesis that the
      mechanism of stroke in migraineurs is most likely because of a paradoxical
      embolus. Future cryptogenic stroke classification schemes should consider
      including PFO as a separate etiologic category.

PMID- 29636428
TI  - Immunomodulatory Effects of Pneumococcal Extracellular Vesicles on Cellular and
      Humoral Host Defenses.
AB  - Gram-positive bacteria, including the major respiratory pathogen Streptococcus
      pneumoniae, were recently shown to produce extracellular vesicles (EVs) that
      likely originate from the plasma membrane and are released into the extracellular
      environment. EVs may function as cargo for many bacterial proteins, however,
      their involvement in cellular processes and their interactions with the innate
      immune system are poorly understood. Here, EVs from pneumococci were
      characterized and their immunomodulatory effects investigated. Pneumococcal EVs
      were protruding from the bacterial surface and released into the medium as 25 to
      250 nm lipid stained vesicles containing a large number of cytosolic, membrane,
      and surface-associated proteins. The cytosolic pore-forming toxin pneumolysin was
      significantly enriched in EVs compared to a total bacterial lysate but was not
      required for EV formation. Pneumococcal EVs were internalized into A549 lung
      epithelial cells and human monocyte-derived dendritic cells and induced
      proinflammatory cytokine responses irrespective of pneumolysin content. EVs from
      encapsulated pneumococci were recognized by serum proteins, resulting in C3b
      deposition and formation of C5b-9 membrane attack complexes as well as factor H
      recruitment, depending on the presence of the choline binding protein PspC.
      Addition of EVs to human serum decreased opsonophagocytic killing of encapsulated
      pneumococci. Our data suggest that EVs may act in an immunomodulatory manner by
      allowing delivery of vesicle-associated proteins and other macromolecules into
      host cells. In addition, EVs expose targets for complement factors in serum,
      promoting pneumococcal evasion of humoral host defense.IMPORTANCEStreptococcus
      pneumoniae is a major contributor to morbidity and mortality worldwide, being the
      major cause of milder respiratory tract infections such as otitis and sinusitis
      and of severe infections such as community-acquired pneumonia, with or without
      septicemia, and meningitis. More knowledge is needed on how pneumococci interact
      with the host, deliver virulence factors, and activate immune defenses. Here we
      show that pneumococci form extracellular vesicles that emanate from the plasma
      membrane and contain virulence properties, including enrichment of pneumolysin.
      We found that pneumococcal vesicles can be internalized into epithelial and
      dendritic cells and bind complement proteins, thereby promoting pneumococcal
      evasion of complement-mediated opsonophagocytosis. They also induce pneumolysin
      independent proinflammatory responses. We suggest that these vesicles can
      function as a mechanism for delivery of pneumococcal proteins and other
      immunomodulatory components into host cells and help pneumococci to avoid
      complement deposition and phagocytosis-mediated killing, thereby possibly
      contributing to the symptoms found in pneumococcal infections.

PMID- 29636429
TI  - Erratum for Basta et al., "Identification of Fitness Determinants during Energy
      Limited Growth Arrest in Pseudomonas aeruginosa".

PMID- 29636430
TI  - Extracellular Electron Transfer Powers Enterococcus faecalis Biofilm Metabolism.
AB  - Enterococci are important human commensals and significant opportunistic
      pathogens. Biofilm-related enterococcal infections, such as endocarditis, urinary
      tract infections, wound and surgical site infections, and medical device
      associated infections, often become chronic upon the formation of biofilm. The
      biofilm matrix establishes properties that distinguish this state from free
      living bacterial cells and increase tolerance to antimicrobial interventions. The
      metabolic versatility of the enterococci is reflected in the diversity and
      complexity of environments and communities in which they thrive. Understanding
      metabolic factors governing colonization and persistence in different host niches
      can reveal factors influencing the transition to biofilm pathogenicity. Here, we
      report a form of iron-dependent metabolism for Enterococcus faecalis where, in
      the absence of heme, extracellular electron transfer (EET) and increased ATP
      production augment biofilm growth. We observe alterations in biofilm matrix depth
      and composition during iron-augmented biofilm growth. We show that the ldh gene
      encoding l-lactate dehydrogenase is required for iron-augmented energy production
      and biofilm formation and promotes EET.IMPORTANCE Bacterial metabolic versatility
      can often influence the outcome of host-pathogen interactions, yet causes of
      metabolic shifts are difficult to resolve. The bacterial biofilm matrix provides
      the structural and functional support that distinguishes this state from free
      living bacterial cells. Here, we show that the biofilm matrix can immobilize
      iron, providing access to this growth-promoting resource which is otherwise
      inaccessible in the planktonic state. Our data show that in the absence of heme,
      Enterococcus faecalis l-lactate dehydrogenase promotes EET and uses matrix
      associated iron to carry out EET. Therefore, the presence of iron within the
      biofilm matrix leads to enhanced biofilm growth.

PMID- 29636431
TI  - Palladin Compensates for the Arp2/3 Complex and Supports Actin Structures during
      Listeria Infections.
AB  - Palladin is an important component of motile actin-rich structures and nucleates
      branched actin filament arrays in vitro Here we examine the role of palladin
      during Listeria monocytogenes infections in order to tease out novel functions of
      palladin. We show that palladin is co-opted by L. monocytogenes during its
      cellular entry and intracellular motility. Depletion of palladin resulted in
      shorter and misshapen comet tails, and when actin- or VASP-binding mutants of
      palladin were overexpressed in cells, comet tails disintegrated or became
      thinner. Comet tail thinning resulted in parallel actin bundles within the
      structures. To determine whether palladin could compensate for the Arp2/3
      complex, we overexpressed palladin in cells treated with the Arp2/3 inhibitor CK
      666. In treated cells, bacterial motility could be initiated and maintained when
      levels of palladin were increased. To confirm these findings, we utilized a cell
      line depleted of multiple Arp2/3 complex subunits. Within these cells, L.
      monocytogenes failed to generate comet tails. When palladin was overexpressed in
      this Arp2/3 functionally null cell line, the ability of L. monocytogenes to
      generate comet tails was restored. Using purified protein components, we
      demonstrate that L. monocytogenes actin clouds and comet tails can be generated
      (in a cell-free system) by palladin in the absence of the Arp2/3 complex.
      Collectively, our results demonstrate that palladin can functionally replace the
      Arp2/3 complex during bacterial actin-based motility.IMPORTANCE Structures
      containing branched actin filaments require the Arp2/3 complex. One of the most
      commonly used systems to study intracellular movement generated by Arp2/3-based
      actin motility exploits actin-rich comet tails made by Listeria Using these
      infections together with live imaging and cell-free protein reconstitution
      experiments, we show that another protein, palladin, can be used in place of
      Arp2/3 to form actin-rich structures. Additionally, we show that palladin is
      needed for the structural integrity of comet tails as its depletion or mutation
      of critical regions causes dramatic changes to comet tail organization. These
      findings are the first to identify a protein that can functionally replace the
      Arp2/3 complex and have implications for all actin-based structures thought to
      exclusively use that complex.

PMID- 29636432
TI  - An Evolutionarily Conserved Mechanism for Intrinsic and Transferable Polymyxin
      Resistance.
AB  - Polymyxins, a family of cationic antimicrobial cyclic peptides, act as a last
      line of defense against severe infections by Gram-negative pathogens with
      carbapenem resistance. In addition to the intrinsic resistance to polymyxin E
      (colistin) conferred by Neisseria eptA, the plasmid-borne mobilized colistin
      resistance gene mcr-1 has been disseminated globally since the first discovery in
      Southern China, in late 2015. However, the molecular mechanisms for both
      intrinsic and transferable resistance to colistin remain largely unknown. Here,
      we aim to address this gap in the knowledge of these proteins. Structural and
      functional analyses of EptA and MCR-1 and -2 have defined a conserved 12-residue
      cavity that is required for the entry of the lipid substrate,
      phosphatidylethanolamine (PE). The in vitro and in vivo data together have
      allowed us to visualize the similarities in catalytic activity shared by EptA and
      MCR-1 and -2. The expression of either EptA or MCR-1 or -2 is shown to remodel
      the surface of enteric bacteria (e.g., Escherichia coli, Salmonella enterica,
      Klebsiella pneumoniae, etc.), rendering them resistant to colistin. The parallels
      in the PE substrate-binding cavities among EptA, MCR-1, and MCR-2 provide a
      comprehensive understanding of both intrinsic and transferable colistin
      resistance. Domain swapping between EptA and MCR-1 and -2 reveals that the two
      domains (transmembrane [TM] region and phosphoethanolamine [PEA] transferase) are
      not functionally exchangeable. Taken together, the results represent a common
      mechanism for intrinsic and transferable PEA resistance to polymyxin, a last
      resort antibiotic against multidrug-resistant pathogens.IMPORTANCE EptA and MCR-1
      and -2 remodel the outer membrane, rendering bacteria resistant to colistin, a
      final resort against carbapenem-resistant pathogens. Structural and functional
      analyses of EptA and MCR-1 and -2 reveal parallel PE lipid substrate-recognizing
      cavities, which explains intrinsic and transferable colistin resistance in gut
      bacteria. A similar mechanism is proposed for the catalytic activities of EptA
      and MCR-1 and -2. Together, they constitute a common mechanism for intrinsic and
      transferable polymyxin resistance.

PMID- 29636433
TI  - Viral Characteristics Associated with the Clinical Nonprogressor Phenotype Are
      Inherited by Viruses from a Cluster of HIV-1 Elite Controllers.
AB  - A small group of HIV-1-infected individuals, called long-term nonprogressors
      (LTNPs), and in particular a subgroup of LTNPs, elite controllers (LTNP-ECs),
      display permanent control of viral replication and lack of clinical progression.
      This control is the result of a complex interaction of host, immune, and viral
      factors. We identified, by phylogenetic analysis, a cluster of LTNP-ECs infected
      with very similar low-replication HIV-1 viruses, suggesting the contribution of
      common viral features to the clinical LTNP-EC phenotype. HIV-1 envelope (Env)
      glycoprotein mediates signaling and promotes HIV-1 fusion, entry, and infection,
      being a key factor of viral fitness in vitro, cytopathicity, and infection
      progression in vivo Therefore, we isolated full-length env genes from viruses of
      these patients and from chronically infected control individuals. Functional
      characterization of the initial events of the viral infection showed that Envs
      from the LTNP-ECs were ineffective in the binding to CD4 and in the key
      triggering of actin/tubulin-cytoskeleton modifications compared to Envs from
      chronic patients. The viral properties of the cluster viruses result in a
      defective viral fusion, entry, and infection, and these properties were inherited
      by every virus of the cluster. Therefore, inefficient HIV-1 Env functions and
      signaling defects may contribute to the low viral replication capacity and
      transmissibility of the cluster viruses, suggesting a direct role in the LTNP-EC
      phenotype of these individuals. These results highlight the important role of
      viral characteristics in the LTNP-EC clinical phenotype. These Env viral
      properties were common to all the cluster viruses and thus support the
      heritability of the viral characteristics.IMPORTANCE HIV-1 long-term
      nonprogressor elite controller patients, due to their permanent control of viral
      replication, have been the object of numerous studies to identify the factors
      responsible for this clinical phenotype. In this work, we analyzed the viral
      characteristics of the envelopes of viruses from a phylogenetic cluster of LTNP
      EC patients. These envelopes showed ineffective binding to CD4 and the subsequent
      signaling activity to modify actin/tubulin cytoskeletons, which result in low
      fusion and deficient entry and infection capacities. These Env viral
      characteristics could explain the nonprogressor clinical phenotype of these
      patients. In addition, these inefficient env viral properties were present in all
      viruses of the cluster, supporting the heritability of the viral phenotype.

PMID- 29636434
TI  - Robust Mercury Methylation across Diverse Methanogenic Archaea.
AB  - Methylmercury (MeHg) production was compared among nine cultured methanogenic
      archaea that contain hgcAB, a gene pair that codes for mercury (Hg) methylation.
      The methanogens tested produced MeHg at inherently different rates, even when
      normalized to growth rate and Hg availability. Eight of the nine tested were
      capable of MeHg production greater than that of spent- and uninoculated-medium
      controls during batch culture growth. Methanococcoides methylutens, an hgcAB+
      strain with a fused gene pair, was unable to produce more MeHg than controls.
      Maximal conversion of Hg to MeHg through a full batch culture growth cycle for
      each species (except M. methylutens) ranged from 2 to >50% of the added Hg(II) or
      between 0.2 and 17 pmol of MeHg/mg of protein. Three of the species produced >10%
      MeHg. The ability to produce MeHg was confirmed in several hgcAB+ methanogens
      that had not previously been tested (Methanocella paludicola SANAE,
      Methanocorpusculum bavaricum, Methanofollis liminatans GKZPZ, and
      Methanosphaerula palustris E1-9c). Maximal methylation was observed at low
      sulfide concentrations (<100 MUM) and in the presence of 0.5 to 5 mM cysteine.
      For M. hollandica, the addition of up to 5 mM cysteine enhanced MeHg production
      and cell growth in a concentration-dependent manner. As observed for bacterial Hg
      methylators, sulfide inhibited MeHg production. An initial evaluation of sulfide
      and thiol impacts on bioavailability showed methanogens responding to Hg
      complexation in the same way as do Deltaproteobacteria The mercury methylation
      rates of several methanogens rival those of the better-studied Hg-methylating
      sulfate- and iron-reducing DeltaproteobacteriaIMPORTANCEArchaea, specifically
      methanogenic organisms, play a role in mercury methylation in nature, but their
      global importance to MeHg production and the subsequent risk to ecosystems are
      not known. Methanogenesis has been linked to Hg methylation in several natural
      habitats where methylmercury production incurs risk to people and ecosystems,
      including rice paddies and permafrost. In this study, we confirm that most
      methanogens carrying the hgcAB gene pair are capable of Hg methylation. We found
      that methylation rates vary inherently among hgcAB+ methanogens but that several
      species are capable of MeHg production at rates that rival those of the better
      know Hg-methylating sulfate- and iron-reducing bacteria. Methanogens may need to
      be considered equally with sulfate and iron reducers in evaluations of MeHg
      production in nature.

PMID- 29636435
TI  - How Polypurine Tract Changes in the HIV-1 RNA Genome Can Cause Resistance against
      the Integrase Inhibitor Dolutegravir.

PMID- 29636436
TI  - Broad-Spectrum Regulation of Nonreceptor Tyrosine Kinases by the Bacterial ADP
      Ribosyltransferase EspJ.
AB  - Tyrosine phosphorylation is key for signal transduction from exogenous stimuli,
      including the defense against pathogens. Conversely, pathogens can subvert
      protein phosphorylation to control host immune responses and facilitate invasion
      and dissemination. The bacterial effectors EspJ and SeoC are injected into host
      cells through a type III secretion system by enteropathogenic and
      enterohemorrhagic Escherichia coli (EPEC and EHEC, respectively), Citrobacter
      rodentium, and Salmonella enterica, where they inhibit Src kinase by coupled
      amidation and ADP-ribosylation. C. rodentium, which is used to model EPEC and
      EHEC infections in humans, is a mouse pathogen triggering colonic crypt
      hyperplasia (CCH) and colitis. Enumeration of bacterial shedding and CCH
      confirmed that EspJ affects neither tolerance nor resistance to infection.
      However, comparison of the proteomes of intestinal epithelial cells isolated from
      mice infected with wild-type C. rodentium or C. rodentium encoding catalytically
      inactive EspJ revealed that EspJ-induced ADP-ribosylation regulates multiple
      nonreceptor tyrosine kinases in vivo Investigation of the substrate repertoire of
      EspJ revealed that in HeLa and A549 cells, Src and Csk were significantly
      targeted; in polarized Caco2 cells, EspJ targeted Src and Csk and the Src family
      kinase (SFK) Yes1, while in differentiated Thp1 cells, EspJ modified Csk, the
      SFKs Hck and Lyn, the Tec family kinases Tec and Btk, and the adapter tyrosine
      kinase Syk. Furthermore, Abl (HeLa and Caco2) and Lyn (Caco2) were enriched
      specifically in the EspJ-containing samples. Biochemical assays revealed that
      EspJ, the only bacterial ADP-ribosyltransferase that targets mammalian kinases,
      controls immune responses and the Src/Csk signaling axis.IMPORTANCE
      Enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC,
      respectively) strains cause significant mortality and morbidity worldwide.
      Citrobacter rodentium is a mouse pathogen used to model EPEC and EHEC
      pathogenesis in vivo Diarrheal disease is triggered following injection of
      bacterial effectors, via a type III secretion system (T3SS), into intestinal
      epithelial cells (IECs). While insights into the role of the effectors were
      historically obtained from pathological, immunologic, or cell culture phenotypes,
      subtle roles of individual effectors in vivo are often masked. The aim of this
      study was to elucidate the role and specificity of the ADP-ribosyltransferase
      effector EspJ. For the first time, we show that the in vivo processes affected by
      a T3SS effector can be studied by comparing the proteomes of IECs extracted from
      mice infected with wild-type C. rodentium or an espJ catalytic mutant. We show
      that EspJ, the only bacterial ADP-ribosyltransferase that targets mammalian
      kinases, regulates the host immune response in vivo.

PMID- 29636437
TI  - Convergent Metabolic Specialization through Distinct Evolutionary Paths in
      Pseudomonas aeruginosa.
AB  - Evolution by natural selection under complex and dynamic environmental conditions
      occurs through intricate and often counterintuitive trajectories affecting many
      genes and metabolic solutions. To study short- and long-term evolution of
      bacteria in vivo, we used the natural model system of cystic fibrosis (CF)
      infection. In this work, we investigated how and through which trajectories
      evolution of Pseudomonas aeruginosa occurs when migrating from the environment to
      the airways of CF patients, and specifically, we determined reduction of growth
      rate and metabolic specialization as signatures of adaptive evolution. We show
      that central metabolic pathways of three distinct Pseudomonas aeruginosa lineages
      coevolving within the same environment become restructured at the cost of
      versatility during long-term colonization. Cell physiology changes from naive to
      adapted phenotypes resulted in (i) alteration of growth potential that
      particularly converged to a slow-growth phenotype, (ii) alteration of nutritional
      requirements due to auxotrophy, (iii) tailored preference for carbon source
      assimilation from CF sputum, (iv) reduced arginine and pyruvate fermentation
      processes, and (v) increased oxygen requirements. Interestingly, although
      convergence was evidenced at the phenotypic level of metabolic specialization,
      comparative genomics disclosed diverse mutational patterns underlying the
      different evolutionary trajectories. Therefore, distinct combinations of genetic
      and regulatory changes converge to common metabolic adaptive trajectories leading
      to within-host metabolic specialization. This study gives new insight into
      bacterial metabolic evolution during long-term colonization of a new
      environmental niche.IMPORTANCE Only a few examples of real-time evolutionary
      investigations in environments outside the laboratory are described in the
      scientific literature. Remembering that biological evolution, as it has
      progressed in nature, has not taken place in test tubes, it is not surprising
      that conclusions from our investigations of bacterial evolution in the CF model
      system are different from what has been concluded from laboratory experiments.
      The analysis presented here of the metabolic and regulatory driving forces
      leading to successful adaptation to a new environment provides an important
      insight into the role of metabolism and its regulatory mechanisms for successful
      adaptation of microorganisms in dynamic and complex environments. Understanding
      the trajectories of adaptation, as well as the mechanisms behind slow growth and
      rewiring of regulatory and metabolic networks, is a key element to understand the
      adaptive robustness and evolvability of bacteria in the process of increasing
      their in vivo fitness when conquering new territories.

PMID- 29636438
TI  - Two Distinct Aerobic Methionine Salvage Pathways Generate Volatile Methanethiol
      in Rhodopseudomonas palustris.
AB  - 5'-Methyl-thioadenosine (MTA) is a dead-end, sulfur-containing metabolite and
      cellular inhibitor that arises from S-adenosyl-l-methionine-dependent reactions.
      Recent studies have indicated that there are diverse bacterial methionine salvage
      pathways (MSPs) for MTA detoxification and sulfur salvage. Here, via a
      combination of gene deletions and directed metabolite detection studies, we
      report that under aerobic conditions the facultatively anaerobic bacterium
      Rhodopseudomonas palustris employs both an MTA-isoprenoid shunt identical to that
      previously described in Rhodospirillum rubrum and a second novel MSP, both of
      which generate a methanethiol intermediate. The additional R. palustris aerobic
      MSP, a dihydroxyacetone phosphate (DHAP)-methanethiol shunt, initially converts
      MTA to 2-(methylthio)ethanol and DHAP. This is identical to the initial steps of
      the recently reported anaerobic ethylene-forming MSP, the DHAP-ethylene shunt.
      The aerobic DHAP-methanethiol shunt then further metabolizes 2
      (methylthio)ethanol to methanethiol, which can be directly utilized by O-acetyl-l
      homoserine sulfhydrylase to regenerate methionine. This is in contrast to the
      anaerobic DHAP-ethylene shunt, which metabolizes 2-(methylthio)ethanol to
      ethylene and an unknown organo-sulfur intermediate, revealing functional
      diversity in MSPs utilizing a 2-(methylthio)ethanol intermediate. When MTA was
      fed to aerobically growing cells, the rate of volatile methanethiol release was
      constant irrespective of the presence of sulfate, suggesting a general
      housekeeping function for these MSPs up through the methanethiol production step.
      Methanethiol and dimethyl sulfide (DMS), two of the most important compounds of
      the global sulfur cycle, appear to arise not only from marine ecosystems but from
      terrestrial ones as well. These results reveal a possible route by which
      methanethiol might be biologically produced in soil and freshwater
      environments.IMPORTANCE Biologically available sulfur is often limiting in the
      environment. Therefore, many organisms have developed methionine salvage pathways
      (MSPs) to recycle sulfur-containing by-products back into the amino acid
      methionine. The metabolically versatile bacterium Rhodopseudomonas palustris is
      unusual in that it possesses two RuBisCOs and two RuBisCO-like proteins. While
      RuBisCO primarily serves as the carbon fixation enzyme of the Calvin cycle,
      RuBisCOs and certain RuBisCO-like proteins have also been shown to function in
      methionine salvage. This work establishes that only one of the R. palustris
      RuBisCO-like proteins functions as part of an MSP. Moreover, in the presence of
      oxygen, to salvage sulfur, R. palustris employs two pathways, both of which
      result in production of volatile methanethiol, a key compound of the global
      sulfur cycle. When total available sulfur was plentiful, methanethiol was readily
      released into the environment. However, when sulfur became limiting, methanethiol
      release decreased, presumably due to methanethiol utilization to regenerate
      needed methionine.

PMID- 29636439
TI  - Hospitalized Premature Infants Are Colonized by Related Bacterial Strains with
      Distinct Proteomic Profiles.
AB  - During the first weeks of life, microbial colonization of the gut impacts human
      immune system maturation and other developmental processes. In premature infants,
      aberrant colonization has been implicated in the onset of necrotizing
      enterocolitis (NEC), a life-threatening intestinal disease. To study the
      premature infant gut colonization process, genome-resolved metagenomics was
      conducted on 343 fecal samples collected during the first 3 months of life from
      35 premature infants housed in a neonatal intensive care unit, 14 of whom
      developed NEC, and metaproteomic measurements were made on 87 samples. Microbial
      community composition and proteomic profiles remained relatively stable on the
      time scale of a week, but the proteome was more variable. Although genetically
      similar organisms colonized many infants, most infants were colonized by distinct
      strains with metabolic profiles that could be distinguished using metaproteomics.
      Microbiome composition correlated with infant, antibiotics administration, and
      NEC diagnosis. Communities were found to cluster into seven primary types, and
      community type switched within infants, sometimes multiple times. Interestingly,
      some communities sampled from the same infant at subsequent time points clustered
      with those of other infants. In some cases, switches preceded onset of NEC;
      however, no species or community type could account for NEC across the majority
      of infants. In addition to a correlation of protein abundances with organism
      replication rates, we found that organism proteomes correlated with overall
      community composition. Thus, this genome-resolved proteomics study demonstrated
      that the contributions of individual organisms to microbiome development depend
      on microbial community context.IMPORTANCE Humans are colonized by microbes at
      birth, a process that is important to health and development. However, much
      remains to be known about the fine-scale microbial dynamics that occur during the
      colonization period. We conducted a genome-resolved study of microbial community
      composition, replication rates, and proteomes during the first 3 months of life
      of both healthy and sick premature infants. Infants were found to be colonized by
      similar microbes, but each underwent a distinct colonization trajectory.
      Interestingly, related microbes colonizing different infants were found to have
      distinct proteomes, indicating that microbiome function is not only driven by
      which organisms are present, but also largely depends on microbial responses to
      the unique set of physiological conditions in the infant gut.

PMID- 29636440
TI  - A Biofilm Matrix-Associated Protease Inhibitor Protects Pseudomonas aeruginosa
      from Proteolytic Attack.
AB  - Pseudomonas aeruginosa produces an extracellular biofilm matrix that consists of
      nucleic acids, exopolysaccharides, lipid vesicles, and proteins. In general, the
      protein component of the biofilm matrix is poorly defined and understudied
      relative to the other major matrix constituents. While matrix proteins have been
      suggested to provide many functions to the biofilm, only proteins that play a
      structural role have been characterized thus far. Here we identify proteins
      enriched in the matrix of P. aeruginosa biofilms. We then focused on a candidate
      matrix protein, the serine protease inhibitor ecotin (PA2755). This protein is
      able to inhibit neutrophil elastase, a bactericidal enzyme produced by the host
      immune system during P. aeruginosa biofilm infections. We show that ecotin binds
      to the key biofilm matrix exopolysaccharide Psl and that it can inhibit
      neutrophil elastase when associated with Psl. Finally, we show that ecotin
      protects both planktonic and biofilm P. aeruginosa cells from neutrophil elastase
      mediated killing. This may represent a novel mechanism of protection for biofilms
      to increase their tolerance against the innate immune response.IMPORTANCE
      Proteins associated with the extracellular matrix of bacterial aggregates called
      biofilms have long been suggested to provide many important functions to the
      community. To date, however, only proteins that provide structural roles have
      been described, and few matrix-associated proteins have been identified. We
      developed a method to identify matrix proteins and characterized one. We show
      that this protein, when associated with the biofilm matrix, can inhibit a
      bactericidal enzyme produced by the immune system during infection and protect
      biofilm cells from death induced by the enzyme. This may represent a novel
      mechanism of protection for biofilms, further increasing their tolerance against
      the immune response. Together, our results are the first to show a nonstructural
      function for a confirmed matrix-interacting protein.

PMID- 29636441
TI  - Anterolateral Bowing of Congenital Pseudoarthrosis of Tibia Treated by
      Percutaneous Osteotomy and Gradual Correction Using Taylor Spatial Frame, then
      Late Insertion of a Fussier-Duval Nail: A Case Report.
AB  - BACKGROUND Congenital pseudoarthrosis of the tibia is one of the most difficult
      orthopedic diseases to treat. Many authors consider osteotomy of the bowed non
      broken tibia a contraindication. However, leaving the patient with a deformed,
      bowed leg is intolerable and is associated with deformity progression and
      increased risk of fracture. CASE REPORT A 12-year-old boy presented with a bowed
      leg. X-ray tibia showed partially healed congenital pseudoarthrosis of the tibia
      and 30 degrees of flexion deformity. Deformity was successfully treated by
      percutaneous osteotomy made through the site of congenital pseudoarthrosis and
      gradual correction using a computer-assisted external fixator, the Taylor spatial
      frame (TSF; Smith and Nephew, Memphis, TN). At the end of the correction, a
      telescopic Fassier-Duval intramedullary nail was used prophylactically to prevent
      re-fracture. After 2 years of follow-up, X-ray images show bone-healing without
      any bowing. CONCLUSIONS Closed percutaneous osteotomy, without excision of the
      pseudoarthrosis, and gradual correction then insertion of Fassier-Duval
      telescopic nail may serve as a treatment to correct deformed bone in congenital
      pseudoarthrosis of the tibia.

PMID- 29636442
TI  - Assessment of Foot Shape in Children and Adolescents with Intellectual
      Disability: A Pilot Study.
AB  - BACKGROUND Available publications provide little evidence pertaining to
      assessment of foot shape in children with intellectual disability. The aim of
      this study was to assess the parameters of foot shape in children and adolescents
      with intellectual disability and to evaluate the relationship between the degree
      of disability and these parameters. MATERIAL AND METHODS The study involved 90
      individuals aged 7-15 years, including 45 subjects with mild and moderate levels
      of intellectual disability (study group) and 45 peers with normal intellectual
      development (control group). Each participant was subjected to photogrammetric
      assessment of foot shape based on the projection moire effect. RESULTS Analysis
      of the relationship between the disability level and the assessed parameters
      showed that the length of the right (p=0.006) and left (p=0.004) foot, as well as
      Wejsflog's rate for the right (p<0.001) and left (p<0.001) foot, were
      significantly higher among children with mild disability, whereas GAMMA angle of
      the right (p=0.028) and left (p=0.006) foot was significantly higher among
      children with moderate disability. CONCLUSIONS The findings show a significant
      relationship between the degree of disability and the assessed foot parameters.
      Significant differences between the subjects with intellectual disability and the
      control group were identified in the basic parameters defining foot structure.

PMID- 29636443
TI  - In situ X-ray imaging of defect and molten pool dynamics in laser additive
      manufacturing.
AB  - The laser-matter interaction and solidification phenomena associated with laser
      additive manufacturing (LAM) remain unclear, slowing its process development and
      optimisation. Here, through in situ and operando high-speed synchrotron X-ray
      imaging, we reveal the underlying physical phenomena during the deposition of the
      first and second layer melt tracks. We show that the laser-induced gas/vapour jet
      promotes the formation of melt tracks and denuded zones via spattering (at a
      velocity of 1 m s-1). We also uncover mechanisms of pore migration by Marangoni
      driven flow (recirculating at a velocity of 0.4 m s-1), pore dissolution and
      dispersion by laser re-melting. We develop a mechanism map for predicting the
      evolution of melt features, changes in melt track morphology from a continuous
      hemi-cylindrical track to disconnected beads with decreasing linear energy
      density and improved molten pool wetting with increasing laser power. Our results
      clarify aspects of the physics behind LAM, which are critical for its
      development.

PMID- 29636444
TI  - Identification of potential urine proteins and microRNA biomarkers for the
      diagnosis of pulmonary tuberculosis patients.
AB  - This study identified urinary biomarkers for tuberculosis (TB) diagnosis. The
      urine proteomic profiles of 45 pulmonary tuberculosis patients prior to anti-TB
      treatment and 45 healthy controls were analyzed and compared using two
      dimensional electrophoresis with matrix-assisted laser desorption/ionization time
      of flight mass spectrometry. Nineteen differentially expressed proteins were
      identified preliminarily, and western blotting and qRT-PCR were performed to
      confirm these changes at the translational and transcriptional levels,
      respectively, using samples from 122 additional pulmonary tuberculosis patients
      and 73 additional healthy controls. Two proteins, mannose-binding lectin 2 and a
      35-kDa fragment of inter-alpha-trypsin inhibitor H4, exhibited the highest
      differential expression. We constructed a protein-microRNA interaction network
      that primarily involved complement and inflammatory responses. Eleven microRNAs
      from microRNA-target protein interactions were screened and validated using qRT
      PCR with some of the above samples, including 97 pulmonary tuberculosis patients
      and 48 healthy controls. Only miR-625-3p exhibited significant differential
      expression (p < 0.05). miR-625-3p was increased to a greater extent in samples of
      smear-positive than smear-negative patients. miR-625-3p was predicted to target
      mannose-binding lectin 2 protein. A binary logistic regression model based on miR
      625-3p, mannose-binding lectin 2, and inter-alpha-trypsin inhibitor H4 was
      further established. This three-biomarker combination exhibited better
      performance for tuberculosis diagnosis than individual biomarkers or any two
      biomarker combination and generated a diagnostic sensitivity of 85.87% and a
      specificity of 87.50%. These novel urine biomarkers may significantly improve
      tuberculosis diagnosis.

PMID- 29636445
TI  - Generation and characterization of ultrathin free-flowing liquid sheets.
AB  - The physics and chemistry of liquid solutions play a central role in science, and
      our understanding of life on Earth. Unfortunately, key tools for interrogating
      aqueous systems, such as infrared and soft X-ray spectroscopy, cannot readily be
      applied because of strong absorption in water. Here we use gas-dynamic forces to
      generate free-flowing, sub-micron, liquid sheets which are two orders of
      magnitude thinner than anything previously reported. Optical, infrared, and X-ray
      spectroscopies are used to characterize the sheets, which are found to be tunable
      in thickness from over 1 MUm  down to less than 20 nm, which corresponds to fewer
      than 100 water molecules thick. At this thickness, aqueous sheets can readily
      transmit photons across the spectrum, leading to potentially transformative
      applications in infrared, X-ray, electron spectroscopies and beyond. The
      ultrathin sheets are stable for days in vacuum, and we demonstrate their use at
      free-electron laser and synchrotron light sources.

PMID- 29636446
TI  - Population genomics of finless porpoises reveal an incipient cetacean species
      adapted to freshwater.
AB  - Cetaceans (whales, dolphins, and porpoises) are a group of mammals adapted to
      various aquatic habitats, from oceans to freshwater rivers. We report the
      sequencing, de novo assembly and analysis of a finless porpoise genome, and the
      re-sequencing of an additional 48 finless porpoise individuals. We use these data
      to reconstruct the demographic history of finless porpoises from their origin to
      the occupation into the Yangtze River. Analyses of selection between marine and
      freshwater porpoises identify genes associated with renal water homeostasis and
      urea cycle, such as urea transporter 2 and angiotensin I-converting enzyme 2,
      which are likely adaptations associated with the difference in osmotic stress
      between ocean and rivers. Our results strongly suggest that the critically
      endangered Yangtze finless porpoises are reproductively isolated from other
      porpoise populations and harbor unique genetic adaptations, supporting that they
      should be considered a unique incipient species.

PMID- 29636447
TI  - The ASIC3/P2X3 cognate receptor is a pain-relevant and ligand-gated cationic
      channel.
AB  - Two subclasses of acid-sensing ion channels (ASIC3) and of ATP-sensitive P2X
      receptors (P2X3Rs) show a partially overlapping expression in sensory neurons.
      Here we report that both recombinant and native receptors interact with each
      other in multiple ways. Current measurements with the patch-clamp technique prove
      that ASIC3 stimulation strongly inhibits the P2X3R current partly by a Ca2+
      dependent mechanism. The proton-binding site is critical for this effect and the
      two receptor channels appear to switch their ionic permeabilities during
      activation. Co-immunoprecipation proves the close association of the two protein
      structures. BN-PAGE and SDS-PAGE analysis is also best reconciled with the view
      that ASIC3 and P2X3Rs form a multiprotein structure. Finally, in vivo
      measurements in rats reveal the summation of pH and purinergically induced pain.
      In conclusion, the receptor subunits do not appear to form a heteromeric channel,
      but tightly associate with each other to form a protein complex, mediating
      unidirectional inhibition.

PMID- 29636448
TI  - Endogenous modulation of human visual cortex activity improves perception at
      twilight.
AB  - Perception, particularly in the visual domain, is drastically influenced by
      rhythmic changes in ambient lighting conditions. Anticipation of daylight changes
      by the circadian system is critical for survival. However, the neural bases of
      time-of-day-dependent modulation in human perception are not yet understood. We
      used fMRI to study brain dynamics during resting-state and close-to-threshold
      visual perception repeatedly at six times of the day. Here we report that resting
      state signal variance drops endogenously at times coinciding with dawn and dusk,
      notably in sensory cortices only. In parallel, perception-related signal variance
      in visual cortices decreases and correlates negatively with detection
      performance, identifying an anticipatory mechanism that compensates for the
      deteriorated visual signal quality at dawn and dusk. Generally, our findings
      imply that decreases in spontaneous neural activity improve close-to-threshold
      perception.

PMID- 29636449
TI  - Distinct molecular pathways mediate Mycn and Myc-regulated miR-17-92 microRNA
      action in Feingold syndrome mouse models.
AB  - Feingold syndrome is a skeletal dysplasia caused by loss-of-function mutations of
      either MYCN (type 1) or MIR17HG that encodes miR-17-92 microRNAs (type 2). Since
      miR-17-92 expression is transcriptionally regulated by MYC transcription factors,
      it has been postulated that Feingold syndrome type 1 and 2 may be caused by a
      common molecular mechanism. Here we show that Mir17-92 deficiency upregulates TGF
      beta signaling, whereas Mycn-deficiency downregulates PI3K signaling in limb
      mesenchymal cells. Genetic or pharmacological inhibition of TGF-beta signaling
      efficiently rescues the skeletal defects caused by Mir17-92 deficiency,
      suggesting that upregulation of TGF-beta signaling is responsible for the
      skeletal defect of Feingold syndrome type 2. By contrast, the skeletal phenotype
      of Mycn-deficiency is partially rescued by Pten heterozygosity, but not by TGF
      beta inhibition. These results strongly suggest that despite the phenotypical
      similarity, distinct molecular mechanisms underlie the pathoetiology for Feingold
      syndrome type 1 and 2.

PMID- 29636450
TI  - Massive mining of publicly available RNA-seq data from human and mouse.
AB  - RNA sequencing (RNA-seq) is the leading technology for genome-wide transcript
      quantification. However, publicly available RNA-seq data is currently provided
      mostly in raw form, a significant barrier for global and integrative
      retrospective analyses. ARCHS4 is a web resource that makes the majority of
      published RNA-seq data from human and mouse available at the gene and transcript
      levels. For developing ARCHS4, available FASTQ files from RNA-seq experiments
      from the Gene Expression Omnibus (GEO) were aligned using a cloud-based
      infrastructure. In total 187,946 samples are accessible through ARCHS4 with
      103,083 mouse and 84,863 human. Additionally, the ARCHS4 web interface provides
      intuitive exploration of the processed data through querying tools, interactive
      visualization, and gene pages that provide average expression across cell lines
      and tissues, top co-expressed genes for each gene, and predicted biological
      functions and protein-protein interactions for each gene based on prior knowledge
      combined with co-expression.

PMID- 29636451
TI  - Quantum metrology with quantum-chaotic sensors.
AB  - Quantum metrology promises high-precision measurements of classical parameters
      with far reaching implications for science and technology. So far, research has
      concentrated almost exclusively on quantum-enhancements in integrable systems,
      such as precessing spins or harmonic oscillators prepared in non-classical
      states. Here we show that large benefits can be drawn from rendering integrable
      quantum sensors chaotic, both in terms of achievable sensitivity as well as
      robustness to noise, while avoiding the challenge of preparing and protecting
      large-scale entanglement. We apply the method to spin-precession magnetometry and
      show in particular that the sensitivity of state-of-the-art magnetometers can be
      further enhanced by subjecting the spin-precession to non-linear kicks that
      renders the dynamics chaotic.

PMID- 29636453
TI  - Publisher Correction: Recent progress and perspectives of space electric
      propulsion systems based on smart nanomaterials.
AB  - The original PDF version of this Article had an incorrect volume number of '8';
      it should have been '9'. This has been corrected in the PDF version of the
      Article. The HTML version was correct from the time of publication.

PMID- 29636454
TI  - Observation of elastic topological states in soft materials.
AB  - Topological elastic metamaterials offer insight into classic motion law and open
      up opportunities in quantum and classic information processing. Theoretical
      modeling and numerical simulation of elastic topological states have been
      reported, whereas the experimental observation remains relatively unexplored.
      Here we present an experimental observation and numerical simulation of tunable
      topological states in soft elastic metamaterials. The on-demand reversible switch
      in topological phase has been achieved by changing filling ratio, tension, and/or
      compression of the elastic metamaterials. By combining two elastic metamaterials
      with distinct topological invariants, we further demonstrate the formation and
      dynamic tunability of topological interface states by mechanical deformation, and
      the manipulation of elastic wave propagation. Moreover, we provide a topological
      phase diagram of elastic metamaterials under deformation. Our approach to
      dynamically control interface states in soft materials paves the way to various
      phononic systems involving thermal management and soft robotics requiring better
      use of energy.

PMID- 29636452
TI  - Species-specific host factors rather than virus-intrinsic virulence determine
      primate lentiviral pathogenicity.
AB  - HIV-1 causes chronic inflammation and AIDS in humans, whereas related simian
      immunodeficiency viruses (SIVs) replicate efficiently in their natural hosts
      without causing disease. It is currently unknown to what extent virus-specific
      properties are responsible for these different clinical outcomes. Here, we
      incorporate two putative HIV-1 virulence determinants, i.e., a Vpu protein that
      antagonizes tetherin and blocks NF-kappaB activation and a Nef protein that fails
      to suppress T cell activation via downmodulation of CD3, into a non-pathogenic
      SIVagm strain and test their impact on viral replication and pathogenicity in
      African green monkeys. Despite sustained high-level viremia over more than 4
      years, moderately increased immune activation and transcriptional signatures of
      inflammation, the HIV-1-like SIVagm does not cause immunodeficiency or any other
      disease. These data indicate that species-specific host factors rather than
      intrinsic viral virulence factors determine the pathogenicity of primate
      lentiviruses.

PMID- 29636456
TI  - Combining CO2 reduction with propane oxidative dehydrogenation over bimetallic
      catalysts.
AB  - The inherent variability and insufficiencies in the co-production of propylene
      from steam crackers has raised concerns regarding the global propylene production
      gap and has directed industry to develop more on-purpose propylene technologies.
      The oxidative dehydrogenation of propane by CO2 (CO2-ODHP) can potentially fill
      this gap while consuming a greenhouse gas. Non-precious FeNi and precious NiPt
      catalysts supported on CeO2 have been identified as promising catalysts for CO2
      ODHP and dry reforming, respectively, in flow reactor studies conducted at 823 K.
      In-situ X-ray absorption spectroscopy measurements revealed the oxidation states
      of metals under reaction conditions and density functional theory calculations
      were utilized to identify the most favorable reaction pathways over the two types
      of catalysts.

PMID- 29636455
TI  - NKX2-5 regulates human cardiomyogenesis via a HEY2 dependent transcriptional
      network.
AB  - Congenital heart defects can be caused by mutations in genes that guide cardiac
      lineage formation. Here, we show deletion of NKX2-5, a critical component of the
      cardiac gene regulatory network, in human embryonic stem cells (hESCs), results
      in impaired cardiomyogenesis, failure to activate VCAM1 and to downregulate the
      progenitor marker PDGFRalpha. Furthermore, NKX2-5 null cardiomyocytes have
      abnormal physiology, with asynchronous contractions and altered action
      potentials. Molecular profiling and genetic rescue experiments demonstrate that
      the bHLH protein HEY2 is a key mediator of NKX2-5 function during human
      cardiomyogenesis. These findings identify HEY2 as a novel component of the NKX2-5
      cardiac transcriptional network, providing tangible evidence that hESC models can
      decipher the complex pathways that regulate early stage human heart development.
      These data provide a human context for the evaluation of pathogenic mutations in
      congenital heart disease.

PMID- 29636457
TI  - The fluorination effect of fluoroamphiphiles in cytosolic protein delivery.
AB  - Direct delivery of proteins into cells avoids many drawbacks of gene delivery,
      and thus has emerging applications in biotherapy. However, it remains a
      challenging task owing to limited charges and relatively large size of proteins.
      Here, we report an efficient protein delivery system via the co-assembly of
      fluoroamphiphiles and proteins into nanoparticles. Fluorous substituents on the
      amphiphiles play essential roles in the formation of uniform nanoparticles,
      avoiding protein denaturation, efficient endocytosis, and maintaining low
      cytotoxicity. Structure-activity relationship studies reveal that longer fluorous
      chain length and higher fluorination degree contribute to more efficient protein
      delivery, but excess fluorophilicity on the polymer leads to the pre-assembly of
      fluoroamphiphiles into stable vesicles, and thus failed protein encapsulation and
      cytosolic delivery. This study highlights the advantage of fluoroamphiphiles over
      other existing strategies for intracellular protein delivery.

PMID- 29636458
TI  - Two genetically diverse H7N7 avian influenza viruses isolated from migratory
      birds in central China.
AB  - After the emergence of H7N9 avian influenza viruses (AIV) in early 2013 in China,
      active surveillance of AIVs in migratory birds was undertaken, and two H7N7
      strains were subsequently recovered from the fresh droppings of migratory birds;
      the strains were from different hosts and sampling sites. Phylogenetic and
      sequence similarity network analyses indicated that several genes of the two H7N7
      viruses were closely related to those in AIVs circulating in domestic poultry,
      although different gene segments were implicated in the two isolates. This
      strongly suggested that genes from viruses infecting migratory birds have been
      introduced into poultry-infecting strains. A Bayesian phylogenetic reconstruction
      of all eight segments implied that multiple reassortments have occurred in the
      evolution of these viruses, particularly during late 2011 and early 2014.
      Antigenic analysis using a hemagglutination inhibition test showed that the two
      H7N7 viruses were moderately cross-reactive with H7N9-specific anti-serum. The
      ability of the two H7N7 viruses to remain infectious under various pH and
      temperature conditions was evaluated, and the viruses persisted the longest at
      near-neutral pH and in cold temperatures. Animal infection experiments showed
      that the viruses were avirulent to mice and could not be recovered from any
      organs. Our results indicate that low pathogenic, divergent H7N7 viruses
      circulate within the East Asian-Australasian flyway. Virus dispersal between
      migratory birds and domestic poultry may increase the risk of the emergence of
      novel unprecedented strains.

PMID- 29636459
TI  - Extraordinary pseudocapacitive energy storage triggered by phase transformation
      in hierarchical vanadium oxides.
AB  - Pseudocapacitance holds great promise for improving energy densities of
      electrochemical supercapacitors, but state-of-the-art pseudocapacitive materials
      show capacitances far below their theoretical values and deliver much lower
      levels of electrical power than carbon-based materials due to poor cation
      accessibility and/or long-range electron transferability. Here we show that in
      situ corundum-to-rutile phase transformation in electron-correlated vanadium
      sesquioxide can yield nonstoichiometric rutile vanadium dioxide layers that are
      composed of highly sodium ion accessible oxygen-deficiency quasi-hexagonal
      tunnels sandwiched between conductive rutile slabs. This unique structure serves
      to boost redox and intercalation kinetics for extraordinary pseudocapacitive
      energy storage in hierarchical isomeric vanadium oxides, leading to a high
      specific capacitance of ~1856 F g-1 (almost sixfold that of the pristine vanadium
      sesquioxide and dioxide) and a bipolar charge/discharge capability at ultrafast
      rates in aqueous electrolyte. Symmetric wide voltage window pseudocapacitors of
      vanadium oxides deliver a power density of ~280 W cm-3 together with an
      exceptionally high volumetric energy density of ~110 mWh cm-3 as well as long
      term cycling stability.

PMID- 29636461
TI  - Increased formate overflow is a hallmark of oxidative cancer.
AB  - Formate overflow coupled to mitochondrial oxidative metabolism? has been observed
      in cancer cell lines, but whether that takes place in the tumor microenvironment
      is not known. Here we report the observation of serine catabolism to formate in
      normal murine tissues, with a relative rate correlating with serine levels and
      the tissue oxidative state. Yet, serine catabolism to formate is increased in the
      transformed tissue of in vivo models of intestinal adenomas and mammary
      carcinomas. The increased serine catabolism to formate is associated with
      increased serum formate levels. Finally, we show that inhibition of formate
      production by genetic interference reduces cancer cell invasion and this
      phenotype can be rescued by exogenous formate. We conclude that increased formate
      overflow is a hallmark of oxidative cancers and that high formate levels promote
      invasion via a yet unknown mechanism.

PMID- 29636462
TI  - Mechanistic insights into allosteric regulation of the A2A adenosine G protein
      coupled receptor by physiological cations.
AB  - Cations play key roles in regulating G-protein-coupled receptors (GPCRs),
      although their mechanisms are poorly understood. Here, 19F NMR is used to
      delineate the effects of cations on functional states of the adenosine A2A GPCR.
      While Na+ reinforces an inactive ensemble and a partial-agonist stabilized state,
      Ca2+ and Mg2+ shift the equilibrium toward active states. Positive allosteric
      effects of divalent cations are more pronounced with agonist and a G-protein
      derived peptide. In cell membranes, divalent cations enhance both the affinity
      and fraction of the high affinity agonist-bound state. Molecular dynamics
      simulations suggest high concentrations of divalent cations bridge specific
      extracellular acidic residues, bringing TM5 and TM6 together at the extracellular
      surface and allosterically driving open the G-protein-binding cleft as shown by
      rigidity-transmission allostery theory. An understanding of cation allostery
      should enable the design of allosteric agents and enhance our understanding of
      GPCR regulation in the cellular milieu.

PMID- 29636460
TI  - CXCR4 involvement in neurodegenerative diseases.
AB  - Neurodegenerative diseases likely share common underlying pathobiology. Although
      prior work has identified susceptibility loci associated with various dementias,
      few, if any, studies have systematically evaluated shared genetic risk across
      several neurodegenerative diseases. Using genome-wide association data from large
      studies (total n = 82,337 cases and controls), we utilized a previously validated
      approach to identify genetic overlap and reveal common pathways between
      progressive supranuclear palsy (PSP), frontotemporal dementia (FTD), Parkinson's
      disease (PD) and Alzheimer's disease (AD). In addition to the MAPT H1 haplotype,
      we identified a variant near the chemokine receptor CXCR4 that was jointly
      associated with increased risk for PSP and PD. Using bioinformatics tools, we
      found strong physical interactions between CXCR4 and four microglia related
      genes, namely CXCL12, TLR2, RALB, and CCR5. Evaluating gene expression from post
      mortem brain tissue, we found that expression of CXCR4 and microglial genes
      functionally related to CXCR4 was dysregulated across a number of
      neurodegenerative diseases. Furthermore, in a mouse model of tauopathy,
      expression of CXCR4 and functionally associated genes was significantly altered
      in regions of the mouse brain that accumulate neurofibrillary tangles most
      robustly. Beyond MAPT, we show dysregulation of CXCR4 expression in PSP, PD, and
      FTD brains, and mouse models of tau pathology. Our multi-modal findings suggest
      that abnormal signaling across a 'network' of microglial genes may contribute to
      neurodegeneration and may have potential implications for clinical trials
      targeting immune dysfunction in patients with neurodegenerative diseases.

PMID- 29636463
TI  - Genomic analysis of oral Campylobacter concisus strains identified a potential
      bacterial molecular marker associated with active Crohn's disease.
AB  - Campylobacter concisus is an oral bacterium that is associated with inflammatory
      bowel disease (IBD) including Crohn's disease (CD) and ulcerative colitis (UC).
      C. concisus consists of two genomospecies (GS) and diverse strains. This study
      aimed to identify molecular markers to differentiate commensal and IBD-associated
      C. concisus strains. The genomes of 63 oral C. concisus strains isolated from
      patients with IBD and healthy controls were examined, of which 38 genomes were
      sequenced in this study. We identified a novel secreted enterotoxin B homologue,
      Csep1. The csep1 gene was found in 56% of GS2 C. concisus strains, presented in
      the plasmid pICON or the chromosome. A six-nucleotide insertion at the position
      654-659 bp in csep1 (csep1-6bpi) was found. The presence of csep1-6bpi in oral C.
      concisus strains isolated from patients with active CD (47%, 7/15) was
      significantly higher than that in strains from healthy controls (0/29, P =
      0.0002), and the prevalence of csep1-6bpi positive C. concisus strains was
      significantly higher in patients with active CD (67%, 4/6) as compared to healthy
      controls (0/23, P = 0.0006). Proteomics analysis detected the Csep1 protein. A
      csep1 gene hot spot in the chromosome of different C. concisus strains was found.
      The pICON plasmid was only found in GS2 strains isolated from the two relapsed CD
      patients with small bowel complications. This study reports a C. concisus
      molecular marker (csep1-6bpi) that is associated with active CD.

PMID- 29636464
TI  - Crab spiders impact floral-signal evolution indirectly through removal of
      florivores.
AB  - The puzzling diversity of flowers is primarily shaped by selection and
      evolutionary change caused by the plant's interaction with animals. The
      contribution of individual animal species to net selection, however, may vary
      depending on the network of interacting organisms. Here we document that in the
      buckler mustard, Biscutella laevigata, the crab spider Thomisus onustus reduces
      bee visits to flowers but also benefits plants by feeding on florivores.
      Uninfested plants experience a trade-off between pollinator and spider attraction
      as both bees and crab spiders are attracted by the floral volatile beta-ocimene.
      This trade-off is reduced by the induced emission of beta-ocimene after florivore
      infestation, which is stronger in plant populations where crab spiders are
      present than where they are absent, suggesting that plants are locally adapted to
      the presence of crab spiders. Our study demonstrates the context-dependence of
      selection and shows how crab spiders impact on floral evolution.

PMID- 29636465
TI  - Burned forests impact water supplies.
AB  - Wildland fire impacts on surface freshwater resources have not previously been
      measured, nor factored into regional water management strategies. But, large
      wildland fires are increasing and raise concerns about fire impacts on potable
      water. Here we synthesize long-term records of wildland fire, climate, and river
      flow for 168 locations across the United States. We show that annual river flow
      changed in 32 locations, where more than 19% of the basin area was burned.
      Wildland fires enhanced annual river flow in the western regions with a warm
      temperate or humid continental climate. Wildland fires increased annual river
      flow most in the semi-arid Lower Colorado region, in spite of frequent droughts
      in this region. In contrast, prescribed burns in the subtropical Southeast did
      not significantly alter river flow. These extremely variable outcomes offer new
      insights into the potential role of wildfire and prescribed fire in regional
      water resource management, under a changing climate.

PMID- 29636466
TI  - Small tumor necrosis factor receptor biologics inhibit the tumor necrosis factor
      p38 signalling axis and inflammation.
AB  - Despite anti-TNF therapy advancements for inflammatory diseases such as
      rheumatoid arthritis, the burden of diseases remains high. An 11-mer TNF peptide,
      TNF70-80, is known to stimulate selective functional responses compared to the
      parent TNF molecule. Here, we show that TNF70-80 binds to the TNF receptor,
      activating p38 MAP kinase through TNF receptor-associated factor 2. Using
      truncated TNFR mutants, we identify the sequence in TNFRI which enables p38
      activation by TNF70-80. Peptides with this TNFRI sequence, such as TNFRI206-211
      bind to TNF and inhibit TNF-induced p38 activation, respiratory burst, cytokine
      production and adhesion receptor expression but not F-Met-Leu-Phe-induced
      respiratory burst in neutrophils. TNFRI206-211 does not prevent TNF binding to
      TNFRI or TNF-induced stimulation of ERK, JNK and NF-kappaB. TNFRI206-211 inhibits
      bacterial lipopolysaccharide-induced peritonitis, carrageenan-induced and antigen
      induced paw inflammation, and respiratory syncytial virus-induced lung
      inflammation in mice. Our findings suggest a way of targeting TNF-p38 pathway to
      treat chronic inflammatory disorders.

PMID- 29636468
TI  - Single-site catalyst promoters accelerate metal-catalyzed nitroarene
      hydrogenation.
AB  - Atomically dispersed supported metal catalysts are drawing wide attention because
      of the opportunities they offer for new catalytic properties combined with
      efficient use of the metals. We extend this class of materials to catalysts that
      incorporate atomically dispersed metal atoms as promoters. The catalysts are used
      for the challenging nitroarene hydrogenation and found to have both high activity
      and selectivity. The promoters are single-site Sn on TiO2 supports that
      incorporate metal nanoparticle catalysts. Represented as M/Sn-TiO2 (M = Au, Ru,
      Pt, Ni), these catalysts decidedly outperform the unpromoted supported metals,
      even for hydrogenation of nitroarenes substituted with various reducible groups.
      The high activity and selectivity of these catalysts result from the creation of
      oxygen vacancies on the TiO2 surface by single-site Sn, which leads to efficient,
      selective activation of the nitro group coupled with a reaction involving
      hydrogen atoms activated on metal nanoparticles.

PMID- 29636467
TI  - Contribution of porcine aminopeptidase N to porcine deltacoronavirus infection.
AB  - Porcine deltacoronavirus (PDCoV), a member of genus Deltacoronavirus, is an
      emerging swine enteropathogenic coronavirus (CoV). Although outstanding efforts
      have led to the identification of Alphacoronavirus and Betacoronavirus receptors,
      the receptor for Deltacoronavirus is unclear. Here, we compared the amino acid
      sequences of several representative CoVs. Phylogenetic analysis showed that PDCoV
      spike (S) protein was close to the cluster containing transmissible
      gastroenteritis virus (TGEV), which utilizes porcine aminopeptidase N (pAPN) as a
      functional receptor. Ectopic expression of pAPN in non-susceptible BHK-21 cells
      rendered them susceptible to PDCoV. These results indicate that pAPN may be a
      functional receptor for PDCoV infection. However, treatment with APN-specific
      antibody and inhibitors did not completely block PDCoV infection in IPI-2I
      porcine intestinal epithelial cells. pAPN knockout in IPI-2I cells completely
      blocked TGEV infection but only slightly decreased PDCoV infection. Homologous
      modeling of pAPN with the S1 C-terminal domain (S1-CTD) of PDCoV or TGEV showed
      that TGEV S1-CTD adopted beta-turns (beta1-beta2 and beta3-beta4), forming the
      tip of a beta-barrel, to recognize pAPN. However, only the top residues in the
      beta1-beta2 turn of PDCoV S1-CTD had the possibility to support an interaction
      with pAPN, and the beta3-beta4 turn failed to contact pAPN. We also discuss the
      evolution and variation of PDCoV S1-CTD based on structure information, providing
      clues to explain the usage of pAPN by PDCoV. Taken together, the results
      presented herein reveal that pAPN is likely not a critical functional receptor
      for PDCoV, although it is involved in PDCoV infection.

PMID- 29636470
TI  - Model evidence for a seasonal bias in Antarctic ice cores.
AB  - Much of the global annual mean temperature change over Quaternary glacial cycles
      can be attributed to slow ice sheet and greenhouse gas feedbacks, but analysis of
      the short-term response to orbital forcings has the potential to reveal key
      relationships in the climate system. In particular, obliquity and precession both
      produce highly seasonal temperature responses at high latitudes. Here, idealized
      single-forcing model experiments are used to quantify Earth's response to
      obliquity, precession, CO2, and ice sheets, and a linear reconstruction
      methodology is used to compare these responses to long proxy records around the
      globe. This comparison reveals mismatches between the annual mean response to
      obliquity and precession in models versus the signals within Antarctic ice cores.
      Weighting the model-based reconstruction toward austral winter or spring reduces
      these discrepancies, providing evidence for a seasonal bias in ice cores.

PMID- 29636469
TI  - Transposon-modified antigen-specific T lymphocytes for sustained therapeutic
      protein delivery in vivo.
AB  - A cell therapy platform permitting long-term delivery of peptide hormones in vivo
      would be a significant advance for patients with hormonal deficiencies. Here we
      report the utility of antigen-specific T lymphocytes as a regulatable peptide
      delivery platform for in vivo therapy. piggyBac transposon modification of murine
      cells with luciferase allows us to visualize T cells after adoptive transfer.
      Vaccination stimulates long-term T-cell engraftment, persistence, and transgene
      expression enabling detection of modified cells up to 300 days after adoptive
      transfer. We demonstrate adoptive transfer of antigen-specific T cells expressing
      erythropoietin (EPO) elevating the hematocrit in mice for more than 20 weeks. We
      extend our observations to human T cells demonstrating inducible EPO production
      from Epstein-Barr virus (EBV) antigen-specific T lymphocytes. Our results reveal
      antigen-specific T lymphocytes to be an effective delivery platform for
      therapeutic molecules such as EPO in vivo, with important implications for other
      diseases that require peptide therapy.

PMID- 29636471
TI  - Response of carbon cycle to drier conditions in the mid-Holocene in central
      China.
AB  - The nature and extent to which hydrological changes induced by the Asian summer
      monsoon affected key biogeochemical processes remain poorly defined. This study
      explores the relationship between peatland drying and carbon cycling on
      centennial timescales in central China using lipid biomarkers. The difference
      between peat n-alkane delta2H and a nearby stalagmite delta18O record reveals
      that intervals of prominent peatland drying occurred during the mid-Holocene.
      Synchronous with these drier conditions, leaf wax delta13C values show large
      negative excursions, with the utilization of CO2 respired from the peatland
      subsurface for plant photosynthesis being a possible mechanism. Crucially,
      successive drying events appear to have had a cumulative impact on the
      susceptibility of peat carbon stores to climate change. Concurrently, bacterially
      derived hopane delta13C values suggest the occurrence of enhanced methane
      oxidation during the drier periods. Collectively, these observations expand our
      understanding of how respiration and degradation of peat are enhanced during
      drying events.

PMID- 29636473
TI  - Recurrent lower respiratory illnesses among young children in rural Kyrgyzstan:
      overuse of antibiotics and possible under-diagnosis of asthma. A qualitative
      FRESH AIR study.
AB  - Lower respiratory tract illnesses (LRT-illnesses) in children under 5 years (U5s)
      are a leading cause of morbidity, hospitalisations and mortality worldwide,
      particularly in low-income countries. It is pertinent to understand possible
      inconsistent management. This study explored perceptions and practices among
      caregivers and health professionals on recurrent LRT-illnesses in U5s. Semi
      structured interviews with 13 caregivers to U5s with recurrent LRT-illnesses and
      with 22 primary care health professional interviews in two rural provinces in
      Kyrgyzstan were triangulated. Data were thematically analysed. The majority
      (8/13) of caregivers described their young children as having recurrent coughing,
      noisy breathing and respiratory distress of whom several had responded positively
      to acute salbutamol and/or had been repeatedly hospitalised for LRT-illness.
      Family stress and financial burdens were significant. The health professionals
      classified young children with recurrent LRT-illnesses primarily with pneumonia
      and/or a multitude of bronchitis diagnoses. Broad-spectrum antibiotics and
      supportive medicine were used repeatedly, prescribed by health professionals or
      purchased un-prescribed by the caregivers at the pharmacy. The health
      professionals had never applied the asthma diagnosis to U5s nor had they
      prescribed inhaled steroids, and none of the interviewed caregivers' U5s were
      diagnosed with asthma. Health professionals and caregivers shared a common
      concern for the children's recurrent respiratory illnesses developing into a
      severe chronic pulmonary condition, including asthma. In conclusion, the study
      identified an inconsistent management of LRT-illnesses in U5s, with exorbitant
      use of antibiotics and an apparently systemic under-diagnosis of asthma/wheeze.
      When the diagnosis asthma is not used, the illness is not considered as a long
      term condition, requiring preventer/controller medication.

PMID- 29636472
TI  - Structural mechanism for nucleotide-driven remodeling of the AAA-ATPase unfoldase
      in the activated human 26S proteasome.
AB  - The proteasome is a sophisticated ATP-dependent molecular machine responsible for
      protein degradation in all known eukaryotic cells. It remains elusive how
      conformational changes of the AAA-ATPase unfoldase in the regulatory particle
      (RP) control the gating of the substrate-translocation channel leading to the
      proteolytic chamber of the core particle (CP). Here we report three alternative
      states of the ATP-gamma-S-bound human proteasome, in which the CP gates are
      asymmetrically open, visualized by cryo-EM at near-atomic resolutions. At least
      four nucleotides are bound to the AAA-ATPase ring in these open-gate states.
      Variation in nucleotide binding gives rise to an axial movement of the pore loops
      narrowing the substrate-translation channel, which exhibit remarkable structural
      transitions between the spiral-staircase and saddle-shaped-circle topologies.
      Gate opening in the CP is thus regulated by nucleotide-driven conformational
      changes of the AAA-ATPase unfoldase. These findings demonstrate an elegant
      mechanism of allosteric coordination among sub-machines within the human
      proteasome holoenzyme.

PMID- 29636474
TI  - A high-strength silicide phase in a stainless steel alloy designed for wear
      resistant applications.
AB  - Hardfacing alloys provide strong, wear-resistant and corrosion-resistant coatings
      for extreme environments such as those within nuclear reactors. Here, we report
      an ultra-high-strength Fe-Cr-Ni silicide phase, named pi-ferrosilicide, within a
      hardfacing Fe-based alloy. Electron diffraction tomography has allowed the
      determination of the atomic structure of this phase. Nanohardness testing
      indicates that the pi-ferrosilicide phase is up to 2.5 times harder than the
      surrounding austenite and ferrite phases. The compressive strength of the pi
      ferrosilicide phase is exceptionally high and does not yield despite loading in
      excess of 1.6 GPa. Such a high-strength silicide phase could not only provide a
      new type of strong, wear-resistant and corrosion-resistant Fe-based coating,
      replacing more costly and hazardous Co-based alloys for nuclear applications, but
      also lead to the development of a new class of high-performance silicide
      strengthened stainless steels, no longer reliant on carbon for strengthening.

PMID- 29636476
TI  - Horn-like space-coiling metamaterials toward simultaneous phase and amplitude
      modulation.
AB  - Acoustic metasurfaces represent a family of planar wavefront-shaping devices
      garnering increasing attention due to their capacity for novel acoustic wave
      manipulation. By precisely tailoring the geometry of these engineered surfaces,
      the effective refractive index may be modulated and, consequently, acoustic phase
      delays tuned. Despite the successful demonstration of phase engineering using
      metasurfaces, amplitude modulation remains overlooked. Herein, we present a class
      of metasurfaces featuring a horn-like space-coiling structure, enabling acoustic
      control with simultaneous phase and amplitude modulation. The functionality of
      this class of metasurfaces, featuring a gradient in channel spacing, has been
      investigated theoretically and numerically and an equivalent model simplifying
      the structural behavior is presented. A metasurface featuring this geometry has
      been designed and its functionality in modifying acoustic radiation patterns
      experimentally validated. This class of acoustic metasurface provides an
      efficient design methodology enabling complete acoustic wave manipulation, which
      may find utility in applications including biomedical imaging, acoustic
      communication, and non-destructive testing.

PMID- 29636475
TI  - ATAC-Seq analysis reveals a widespread decrease of chromatin accessibility in age
      related macular degeneration.
AB  - Age-related macular degeneration (AMD) is a significant cause of vision loss in
      the elderly. The extent to which epigenetic changes regulate AMD progression is
      unclear. Here we globally profile chromatin accessibility using ATAC-Seq in the
      retina and retinal pigmented epithelium (RPE) from AMD and control patients.
      Global decreases in chromatin accessibility occur in the RPE with early AMD, and
      in the retina of advanced disease, suggesting that dysfunction in the RPE drives
      disease onset. Footprints of photoreceptor and RPE-specific transcription factors
      are enriched in differentially accessible regions (DARs). Genes associated with
      DARs show altered expression in AMD. Cigarette smoke treatment of RPE cells
      recapitulates chromatin accessibility changes seen in AMD, providing an
      epigenetic link between a known risk factor for AMD and AMD pathology. Finally,
      overexpression of HDAC11 is partially responsible for the observed reduction in
      chromatin accessibility, suggesting that HDAC11 may be a potential new
      therapeutic target for AMD.

PMID- 29636478
TI  - Magnetically-driven phase transformation strengthening in high entropy alloys.
AB  - CrCoNi alloy exhibits a remarkable combination of strength and plastic
      deformation, even superior to the CrMnFeCoNi high-entropy alloy. We connect the
      magnetic and mechanical properties of CrCoNi, via a magnetically tunable phase
      transformation. While both alloys crystallize as single-phase face-centered-cubic
      (fcc) solid solutions, we find a distinctly lower-energy phase in CrCoNi alloy
      with a hexagonal close-packed (hcp) structure. Comparing the magnetic
      configurations of CrCoNi with those of other equiatomic ternary derivatives of
      CrMnFeCoNi confirms that magnetically frustrated Mn eliminates the fcc-hcp energy
      difference. This highlights the unique combination of chemistry and magnetic
      properties in CrCoNi, leading to a fcc-hcp phase transformation that occurs only
      in this alloy, and is triggered by dislocation slip and interaction with internal
      boundaries. This phase transformation sets CrCoNi apart from the parent quinary,
      and its other equiatomic ternary derivatives, and provides a new way for
      increasing strength without compromising plastic deformation.

PMID- 29636479
TI  - Negative circular polarization emissions from WSe2/MoSe2 commensurate
      heterobilayers.
AB  - Van der Waals heterobilayers of transition metal dichalcogenides with spin-valley
      coupling of carriers in different layers have emerged as a new platform for
      exploring spin/valleytronic applications. The interlayer coupling was predicted
      to exhibit subtle changes with the interlayer atomic registry. Manually stacked
      heterobilayers, however, are incommensurate with the inevitable interlayer twist
      and/or lattice mismatch, where the properties associated with atomic registry are
      difficult to access by optical means. Here, we unveil the distinct polarization
      properties of valley-specific interlayer excitons using epitaxially grown,
      commensurate WSe2/MoSe2 heterobilayers with well-defined (AA and AB) atomic
      registry. We observe circularly polarized photoluminescence from interlayer
      excitons, but with a helicity opposite to the optical excitation. The negative
      circular polarization arises from the quantum interference imposed by interlayer
      atomic registry, giving rise to distinct polarization selection rules for
      interlayer excitons. Using selective excitation schemes, we demonstrate the
      optical addressability for interlayer excitons with different valley
      configurations and polarization helicities.

PMID- 29636477
TI  - Characterization of PIK3CA and PIK3R1 somatic mutations in Chinese breast cancer
      patients.
AB  - Deregulation of the phosphoinositide 3-kinase (PI3K) pathway contributes to the
      development and progression of tumors. Here, we determine that somatic mutations
      in PIK3CA (44%), PIK3R1 (17%), AKT3 (15%), and PTEN (12%) are prevalent and
      diverse in Chinese breast cancer patients, with 60 novel mutations identified. A
      high proportion of tumors harbors multiple mutations, especially PIK3CA plus
      PIK3R1 mutations (9.0%). Next, we develop a recombination-based mutation
      barcoding (ReMB) library for impactful mutations conferring clonal advantage in
      proliferation and drug responses. The highest-ranking PIK3CA and PIK3R1 mutations
      include previously reported deleterious mutations, as well as mutations with
      unknown significance. These PIK3CA and PIK3R1 impactful mutations exhibit a
      mutually exclusive pattern, leading to oncogenesis and hyperactivity of PI3K
      pathway. The PIK3CA impactful mutations are tightly associated with hormone
      receptor positivity. Collectively, these findings advance our understanding of
      PI3K impactful mutations in breast cancer and have important implications for
      PI3K-targeted therapy in precision oncology.

PMID- 29636480
TI  - Entropy favors heterogeneous structures of networks near the rigidity threshold.
AB  - The dynamical properties and mechanical functions of amorphous materials are
      governed by their microscopic structures, particularly the elasticity of the
      interaction networks, which is generally complicated by structural heterogeneity.
      This ubiquitous heterogeneous nature of amorphous materials is intriguingly
      attributed to a complex role of entropy. Here, we show in disordered networks
      that the vibrational entropy increases by creating phase-separated structures
      when the interaction connectivity is close to the onset of network rigidity. The
      stress energy, which conversely penalizes the heterogeneity, finally dominates a
      smaller vicinity of the rigidity threshold at the glass transition and creates a
      homogeneous intermediate phase. This picture of structures changing between
      homogeneous and heterogeneous phases by varying connectivity provides an
      interpretation of the transitions observed in chalcogenide glasses.

PMID- 29636481
TI  - A NIGT1-centred transcriptional cascade regulates nitrate signalling and
      incorporates phosphorus starvation signals in Arabidopsis.
AB  - Nitrate is a nutrient signal that triggers complex regulation of transcriptional
      networks to modulate nutrient-dependent growth and development in plants. This
      includes time- and nitrate concentration-dependent regulation of nitrate-related
      gene expression. However, the underlying mechanisms remain poorly understood.
      Here we identify NIGT1 transcriptional repressors as negative regulators of the
      Arabidopsis NRT2.1 nitrate transporter gene, and show antagonistic regulation by
      NLP primary transcription factors for nitrate signalling and the NLP-NIGT1
      transcriptional cascade-mediated repression. This antagonistic regulation
      provides a resolution to the complexity of nitrate-induced transcriptional
      regulations. Genome-wide analysis reveals that this mechanism is applicable to
      NRT2.1 and other genes involved in nitrate assimilation, hormone biosynthesis and
      transcription. Furthermore, the PHR1 master regulator of the phosphorus
      starvation response also directly promotes expression of NIGT1 family genes,
      leading to reductions in nitrate uptake. NIGT1 repressors thus act in two
      transcriptional cascades, forming a direct link between phosphorus and nitrogen
      nutritional regulation.

PMID- 29636482
TI  - Longer and more frequent marine heatwaves over the past century.
AB  - Heatwaves are important climatic extremes in atmospheric and oceanic systems that
      can have devastating and long-term impacts on ecosystems, with subsequent
      socioeconomic consequences. Recent prominent marine heatwaves have attracted
      considerable scientific and public interest. Despite this, a comprehensive
      assessment of how these ocean temperature extremes have been changing globally is
      missing. Using a range of ocean temperature data including global records of
      daily satellite observations, daily in situ measurements and gridded monthly in
      situ-based data sets, we identify significant increases in marine heatwaves over
      the past century. We find that from 1925 to 2016, global average marine heatwave
      frequency and duration increased by 34% and 17%, respectively, resulting in a 54%
      increase in annual marine heatwave days globally. Importantly, these trends can
      largely be explained by increases in mean ocean temperatures, suggesting that we
      can expect further increases in marine heatwave days under continued global
      warming.

PMID- 29636483
TI  - ENSO-driven climate variability promotes periodic major outbreaks of dengue in
      Venezuela.
AB  - Dengue is a mosquito-borne viral disease of global impact. In Venezuela, dengue
      has emerged as one of the most important public health problems of urban areas
      with frequent epidemics since 2001. The long-term pattern of this disease has
      involved not only a general upward trend in cases but also a dramatic increase in
      the size and frequency of epidemic outbreaks. By assuming that climate
      variability has a relevant influence on these changes in time, we quantified the
      periodicity of dengue incidence in time-series of data from two northern regions
      of Venezuela. Disease cycles of 1 and 3-4 years (p < 0.05) were detected. We
      determined that dengue cycles corresponded with local climate and the El Nino
      Southern Oscillation (ENSO) variation at both seasonal and inter-annual scales
      (every 2-3 years). Dengue incidence peaks were more prevalent during the warmer
      and dryer years of El Nino confirming that ENSO is a regional climatic driver of
      such long-term periodicity through local changes in temperature and rainfall. Our
      findings support the evidence of the effect of climate on dengue dynamics and
      advocate the incorporation of climate information in the surveillance and
      prediction of this arboviral disease in Venezuela.

PMID- 29636484
TI  - Growth mechanism of epitaxial YSZ on Si by Pulsed Laser Deposition.
AB  - The epitaxial growth of yttria-stabilized zirconia (YSZ) on silicon with native
      oxide was investigated in order to gain more insight in the growth mechanism.
      Specifically, attention was paid to the possibilities to control the chemical
      interactions between YSZ, silicon and oxygen during initial growth. The sources
      of oxygen during growth proved to play an important role in the growth process,
      as shown by individual manipulation of all sources present during Pulsed Laser
      Deposition. Partial oxidation of the YSZ plasma and sufficient delivery of oxygen
      to the growing film were necessary to prevent silicide formation and obtain
      optimal YSZ crystalline qualities. In these conditions, thickness increase of the
      silicon native oxide before growth just started to occur, while a much faster
      regrowth of silicon oxide at the YSZ-Si interface occurred during growth. Control
      of all these contributions to the growth process is necessary to obtain
      reproducible growth of high quality YSZ.

PMID- 29636486
TI  - The tremendous potential of deep-sea mud as a source of rare-earth elements.
AB  - Potential risks of supply shortages for critical metals including rare-earth
      elements and yttrium (REY) have spurred great interest in commercial mining of
      deep-sea mineral resources. Deep-sea mud containing over 5,000 ppm total REY
      content was discovered in the western North Pacific Ocean near Minamitorishima
      Island, Japan, in 2013. This REY-rich mud has great potential as a rare-earth
      metal resource because of the enormous amount available and its advantageous
      mineralogical features. Here, we estimated the resource amount in REY-rich mud
      with Geographical Information System software and established a mineral
      processing procedure to greatly enhance its economic value. The resource amount
      was estimated to be 1.2 Mt of rare-earth oxide for the most promising area (105
      km2 * 0-10 mbsf), which accounts for 62, 47, 32, and 56 years of annual global
      demand for Y, Eu, Tb, and Dy, respectively. Moreover, using a hydrocyclone
      separator enabled us to recover selectively biogenic calcium phosphate grains,
      which have high REY content (up to 22,000 ppm) and constitute the coarser domain
      in the grain-size distribution. The enormous resource amount and the
      effectiveness of the mineral processing are strong indicators that this new REY
      resource could be exploited in the near future.

PMID- 29636487
TI  - Zn-based eutectic mixture as anolyte for hybrid redox flow batteries.
AB  - Developing greener batteries with new chemistries is a formidable challenge, and
      a major focus for years to come. Redox flow batteries are receiving increasing
      research interest for grid-scale electrochemical energy storage owing to their
      unique architecture. However, challenges still remain by their low energy density
      as well as corrosive and/or toxic electrolytes. An anolyte based on aprotic Zn
      deep-eutectic-solvent, which uses low cost, abundant and environmentally benign
      materials, exhibits a utilizable concentration of Zn2+ ca. 1.7 M, resulting in a
      reversible volumetric capacity of ca. 90 A h.L-1. Combined with high efficiencies
      and relatively low redox potential of -1.12 V vs. Ag/AgCl, such an anolyte
      provides an alternative way to explore a family of anolytes using new chemistries
      for rechargeable Zn batteries that meet the criteria for grid-scale electrical
      energy storage.

PMID- 29636485
TI  - Antagonistic PCP Signaling Pathways in the developing Drosophila eye.
AB  - In Planar cell polarity (PCP), cells coordinately polarize their cytoskeletons
      within the plane of the epithelium in which they lie. In most insect epithelia
      this is indicated by the coordinated projections of the hairs secreted by the
      ectodermal cells. PCP of this form has been effectively studied in Drosophila,
      but it has proven difficult to achieve an integrated description of the roles
      played by the various proteins. In the insect eye, PCP is not evident as the
      polarization of individual cells, but as the asymmetric arrangements of the cells
      of the ommatidia. This different form of PCP allows different studies to be
      performed, and using this system we have detected the action of two antagonistic
      signaling pathways. Even though antagonistic, the two pathways synergize and
      cooperate to ensure that the correct arrangement of the cells is achieved. The
      cooperative use of antagonistic signaling pathways occurs in the polarization of
      chemotacting cells, and we discuss the possibility that a similar molecular
      principle may underlie PCP.

PMID- 29636488
TI  - Al-Coated Conductive Fiber Filters for High-Efficiency Electrostatic Filtration:
      Effects of Electrical and Fiber Structural Properties.
AB  - Through the direct decomposition of an Al precursor ink AlH3{O(C4H9)2}, we
      fabricated an Al-coated conductive fiber filter for the efficient electrostatic
      removal of airborne particles (>99%) with a low pressure drop (~several Pascals).
      The effects of the electrical and structural properties of the filters were
      investigated in terms of collection efficiency, pressure drop, and particle
      deposition behavior. The collection efficiency did not show a significant
      correlation with the extent of electrical conductivity, as the filter is
      electrostatically charged by the metallic Al layers forming electrical networks
      throughout the fibers. Most of the charged particles were collected via surface
      filtration by Coulombic interactions; consequently, the filter thickness had
      little effect on the collection efficiency. Based on simulations of various fiber
      structures, we found that surface filtration can transition to depth filtration
      depending on the extent of interfiber distance. Therefore, the effects of
      structural characteristics on collection efficiency varied depending on the
      degree of the fiber packing density. This study will offer valuable information
      pertaining to the development of a conductive metal/polymer composite air filter
      for an energy-efficient and high-performance electrostatic filtration system.

PMID- 29636489
TI  - In-situ, In-Memory Stateful Vector Logic Operations based on Voltage Controlled
      Magnetic Anisotropy.
AB  - Recently, the exponential increase in compute requirements demanded by emerging
      applications like artificial intelligence, Internet of things, etc. have rendered
      the state-of-art von-Neumann machines inefficient in terms of energy and
      throughput owing to the well-known von-Neumann bottleneck. A promising approach
      to mitigate the bottleneck is to do computations as close to the memory units as
      possible. One extreme possibility is to do in-situ Boolean logic computations by
      using stateful devices. Stateful devices are those that can act both as a compute
      engine and storage device, simultaneously. We propose such stateful, vector, in
      memory operations using voltage controlled magnetic anisotropy (VCMA) effect in
      magnetic tunnel junctions (MTJ). Our proposal is based on the well known
      manufacturable 1-transistor - 1-MTJ bit-cell and does not require any
      modifications in the bit-cell circuit or the magnetic device. Instead, we
      leverage the very physics of the VCMA effect to enable stateful computations.
      Specifically, we exploit the voltage asymmetry of the VCMA effect to construct
      stateful IMP (implication) gate and use the precessional switching dynamics of
      the VCMA devices to propose a massively parallel NOT operation. Further, we show
      that other gates like AND, OR, NAND, NOR, NIMP (complement of implication) can be
      implemented using multi-cycle operations.

PMID- 29636490
TI  - Contrasting epigenetic states of heterochromatin in the different types of mouse
      pluripotent stem cells.
AB  - Mouse embryonic stem cells (ESCs) and epiblast stem cells (EpiSCs) represent
      naive and primed pluripotency states, respectively, and are maintained in vitro
      by specific signalling pathways. Furthermore, ESCs cultured in serum-free medium
      with two kinase inhibitors (2i-ESCs) are thought to be the ground naive
      pluripotent state. Here, we present a comparative study of the epigenetic and
      transcriptional states of pericentromeric heterochromatin satellite sequences
      found in these pluripotent states. We show that 2i-ESCs are distinguished from
      other pluripotent cells by a prominent enrichment in H3K27me3 and low levels of
      DNA methylation at pericentromeric heterochromatin. In contrast, serum-containing
      ESCs exhibit higher levels of major satellite repeat transcription, which is
      lower in 2i-ESCs and even more repressed in primed EpiSCs. Removal of either DNA
      methylation or H3K9me3 at PCH in 2i-ESCs leads to enhanced deposition of H3K27me3
      with few changes in satellite transcript levels. In contrast, their removal in
      EpiSCs does not lead to deposition of H3K27me3 but rather removes transcriptional
      repression. Altogether, our data show that the epigenetic state of PCH is
      modified during transition from naive to primed pluripotency states towards a
      more repressive state, which tightly represses the transcription of satellite
      repeats.

PMID- 29636492
TI  - Detector-device-independent quantum secret sharing with source flaws.
AB  - Measurement-device-independent entanglement witness (MDI-EW) plays an important
      role for detecting entanglement with untrusted measurement device. We present a
      double blinding-attack on a quantum secret sharing (QSS) protocol based on GHZ
      state. Using the MDI-EW method, we propose a QSS protocol against all detector
      side-channels. We allow source flaws in practical QSS system, so that Charlie can
      securely distribute a key between the two agents Alice and Bob over long
      distances. Our protocol provides condition on the extracted key rate for the
      secret against both external eavesdropper and arbitrary dishonest participants. A
      tight bound for collective attacks can provide good bounds on the practical QSS
      with source flaws. Then we show through numerical simulations that using single
      photon source a secure QSS over 136 km can be achieved.

PMID- 29636491
TI  - Stimulation of TLR3 triggers release of lysosomal ATP in astrocytes and
      epithelial cells that requires TRPML1 channels.
AB  - Cross-reactions between innate immunity, lysosomal function, and purinergic
      pathways may link signaling systems in cellular pathologies. We found activation
      of toll-like receptor 3 (TLR3) triggers lysosomal ATP release from both
      astrocytes and retinal pigmented epithelial (RPE) cells. ATP efflux was
      accompanied by lysosomal acid phosphatase and beta hexosaminidase release.
      Poly(I:C) alkalinized lysosomes, and lysosomal alkalization with bafilomycin or
      chloroquine triggered ATP release. Lysosomal rupture with glycyl-L-phenylalanine
      2-naphthylamide (GPN) eliminated both ATP and acid phosphatase release. Secretory
      lysosome marker LAMP3 colocalized with VNUT, while MANT-ATP colocalized with
      LysoTracker. Unmodified membrane-impermeant 21-nt and "non-targeting" scrambled
      21-nt siRNA triggered ATP and acid phosphatase release, while smaller 16-nt RNA
      was ineffective. Poly(I:C)-dependent ATP release was reduced by TBK-1 block and
      in TRPML1-/- cells, while TRPML activation with ML-SA1 was sufficient to release
      both ATP and acid phosphatase. The ability of poly(I:C) to raise cytoplasmic Ca2+
      was abolished by removing extracellular ATP with apyrase, suggesting ATP release
      by poly(I:C) increased cellular signaling. Starvation but not rapamycin prevented
      lysosomal ATP release. In summary, stimulation of TLR3 triggers lysosomal
      alkalization and release of lysosomal ATP through activation of TRPML1; this
      links innate immunity to purinergic signaling via lysosomal physiology, and
      suggests even scrambled siRNA can influence these pathways.

PMID- 29636493
TI  - Cross-species analysis of apical asparagine-rich protein of Plasmodium vivax and
      Plasmodium knowlesi.
AB  - The Plasmodium falciparum apical asparagine (Asn)-rich protein (AARP) is one of
      malarial proteins, and it has been studied as a candidate of malaria subunit
      vaccine. Basic characterization of PvAARP has been performed with a focus on its
      immunogenicity and localization. In this study, we further analyzed the
      immunogenicity of PvAARP, focusing on the longevity of the antibody response,
      cross-species immunity and invasion inhibitory activity by using the primate
      malaria parasite Plasmodium knowlesi. We found that vivax malaria patient sera
      retained anti-PvAARP antibodies for at least one year without re-infection.
      Recombinant PvAARP protein was strongly recognized by knowlesi malaria patients.
      Antibody raised against the P. vivax and P. knowlesi AARP N-termini reacted with
      the apical side of the P. knowlesi merozoites and inhibited erythrocyte invasion
      by P. knowlesi in a concentration-dependent manner, thereby suggesting a cross
      species nature of anti-PvAARP antibody against PkAARP. These results can be
      explained by B cell epitopes predicted in conserved surface-exposed regions of
      the AARP N-terminus in both species. The long-lived anti-PvAARP antibody
      response, cross-reactivity, and invasion inhibitory activity of anti-PvAARP
      support a critical role of AARP during the erythrocyte invasion and suggest that
      PvAARP induces long-lived cross-species protective immunity against P. vivax and
      P. knowlesi.

PMID- 29636494
TI  - Variable density dependence and the restructuring of coral-reef fisheries across
      25 years of exploitation.
AB  - Variable density dependence within multispecies fisheries results in species
      restructuring as exploitation intensifies that is poorly understood. We examined
      unique species-based records across 25 years of exploitation to evaluate
      patterns, consequences, and predictions of species replacements within three
      coral-reef fisheries. Body-size was an expected determinant of species
      replacements, as larger fishes were consistently replaced by smaller, faster
      growing counterparts. However, many species with similar sizes and growth rates
      responded differently. Naso unicornis, a primary component of coral-reef
      fisheries across the Pacific, was one of the most resilient species to
      exploitation despite having a similar maximum size and growth as many large
      parrotfishes that slowly disappeared from landings. Assessments conducted for all
      primary target species revealed clear distinctions in compensatory responses: 31%
      had diminishing size structures, 18% had diminishing proportional contribution,
      but only 5% showed both. Standard approaches to fisheries management assume
      constant rates of size-and-age restructuring and rely upon metrics such as
      fishing-versus-natural mortality. Instead, a deeper appreciation for varying
      recruitment rates may help to (re)define fisheries management units and reduce
      complexity in multispecies fisheries. We last consider our results alongside
      traditional knowledge and management in the Pacific that clearly appreciated
      species responses, but have been lost over the years.

PMID- 29636495
TI  - Exchange-torque-induced excitation of perpendicular standing spin waves in
      nanometer-thick YIG films.
AB  - Spin waves in ferrimagnetic yttrium iron garnet (YIG) films with ultralow
      magnetic damping are relevant for magnon-based spintronics and low-power wave
      like computing. The excitation frequency of spin waves in YIG is rather low in
      weak external magnetic fields because of its small saturation magnetization,
      which limits the potential of YIG films for high-frequency applications. Here, we
      demonstrate how exchange-coupling to a CoFeB film enables efficient excitation of
      high-frequency perpendicular standing spin waves (PSSWs) in nanometer-thick (80
      nm and 295 nm) YIG films using uniform microwave magnetic fields. In the 295-nm
      thick YIG film, we measure intense PSSW modes up to 10th order. Strong
      hybridization between the PSSW modes and the ferromagnetic resonance mode of
      CoFeB leads to characteristic anti-crossing behavior in broadband spin-wave
      spectra. We explain the excitation of PSSWs by exchange coupling between forced
      magnetization precessions in the YIG and CoFeB layers. If the amplitudes of these
      precessions are different, a dynamic exchange torque is generated, causing the
      emission of spin waves from the interface. PSSWs form when the wave vector of the
      spin waves matches a perpendicular confinement condition. PSSWs are not excited
      if exchange coupling between YIG and CoFeB is eliminated by a 10 nm Ta spacer
      layer. Micromagnetic simulations confirm the exchange-torque-driven mechanism.

PMID- 29636496
TI  - Functionalization of beta-lactam antibiotic on lysozyme capped gold nanoclusters
      retrogress MRSA and its persisters following awakening.
AB  - In this study we have reported an efficient antibacterial hybrid fabricated
      through surface functionalization of lysozyme capped gold nanoclusters (AUNC-L)
      with beta-lactam antibiotic ampicillin (AUNC-L-Amp). The prepared hybrid not only
      reverted the MRSA resistance towards ampicillin but also demonstrated enhanced
      antibacterial activity against non-resistant bacterial strains. Most importantly,
      upon awakening through cis-2-decenoic acid (cis-DA) exposure, the MRSA persister
      got inhibited by the AUNC-L-Amp treatment. Intraperitoneal administration of this
      hybrid eliminates the systemic MRSA infection in a murine animal model. Topical
      application of this nano conjugate eradicated MRSA infection from difficult to
      treat diabetic wound of rat and accelerated the healing process. Due to inherent
      bio-safe nature of gold, AUNC-L alone or in the construct (AUNC-L-Amp)
      demonstrated excellent biocompatibility and did not indicate any deleterious
      effects in in vivo settings. We postulate that AUNC-L-Amp overcomes the elevated
      levels of beta-lactamase at the site of MRSA antibiotic interaction with
      subsequent multivalent binding to the bacterial surface and enhanced permeation.
      Coordinated action of AUNC-L-Amp components precludes MRSA to attain resistance
      against the hybrid. We proposed that the inhibitory effect of AUNC-L-Amp against
      MRSA and its persister form is due to increased Amp concentration at the site of
      action, multivalent presentation and enhanced permeation of Amp through lysozyme
      mediated cell wall lysis.

PMID- 29636497
TI  - Arousing emoticons edit stream/bounce perception of objects moving past each
      other.
AB  - When two identical objects move toward each other, overlap completely, and
      continue toward opposite ends of a space, observers might perceive them as
      streaming through or bouncing off each other. This phenomenon is known as
      'stream/bounce perception'. In this study, we investigated the effect of the
      presentation of emoticons on stream/bounce perception in five experiments. In
      Experiment 1, we used emoticons representing anger ('('?')'), a smile ('(^_^)'),
      and a sober face ('( degrees _ degrees )', as a control), and observers were
      asked to judge whether two objects unrelated to the emoticon had streamed through
      or bounced off each other. The anger emoticon biased perception toward bouncing
      when compared with the smile or sober face emoticon. In Experiments 2 and 3, we
      controlled for the valence and arousal of emoticons, and found that arousal
      influenced stream/bounce perception but valence did not. Experiments 4 and 5
      ruled out the possibility of attentional capture and response bias for the
      emoticon with higher arousal. Taken together, the findings indicate that
      emoticons with higher arousal evoke a mental image of a 'collision' in observers,
      thereby eliciting the bounce perception.

PMID- 29636498
TI  - Up-conversion luminescence, temperature sensing properties and laser-induced
      heating effect of Er3+/Yb3+ co-doped YNbO4 phosphors under 1550 nm excitation.
AB  - YNbO4 phosphors with various Er3+ and Yb3+ concentrations were synthesized via a
      traditional high-temperature solid-state reaction method. Their crystal structure
      was investigated by means of X-ray diffraction (XRD) and Rietveld refinements,
      and it was confirmed that the obtained samples exist in monoclinic phase. The
      Er3+ and Yb3+ concentration-dependent up-conversion (UC) luminescence was studied
      under 1550 nm excitation. By inspecting the dependence of UC intensity on the
      laser working current, it was found that four-photon and three-photon population
      processes were co-existent for generating the green UC emissions in the samples
      with higher Yb3+ concentrations. In addition, it was observed that the
      temperature sensing properties of YNbO4: Er3+/Yb3+ phosphors were sensitive to
      both Er3+ and Yb3+ doping concentrations. Furthermore, based on the obtained
      temperature response of the UC luminescence phosphors, 1550 nm laser-irradiation
      induced thermal effect was studied, and it was discovered that the sample
      temperature was very sensitive to the doping concentrations of Er3+ and Yb3+ and
      the excitation power.

PMID- 29636499
TI  - Non-uniform weighting of local motion inputs underlies dendritic computation in
      the fly visual system.
AB  - The fly visual system offers a unique opportunity to explore computations
      performed by single neurons. Two previous studies characterized, in vivo, the
      receptive field (RF) of the vertical system (VS) cells of the blowfly (calliphora
      vicina), both intracellularly in the axon, and, independently using Ca2+ imaging,
      in hundreds of distal dendritic branchlets. We integrated this information into
      detailed passive cable and compartmental models of 3D reconstructed VS cells.
      Within a given VS cell type, the transfer resistance (TR) from different
      branchlets to the axon differs substantially, suggesting that they contribute
      unequally to the shaping of the axonal RF. Weighting the local RFs of all
      dendritic branchlets by their respective TR yielded a faithful reproduction of
      the axonal RF. The model also predicted that the various dendritic branchlets are
      electrically decoupled from each other, thus acting as independent local
      functional subunits. The study suggests that single neurons in the fly visual
      system filter dendritic noise and compute the weighted average of their inputs.

PMID- 29636500
TI  - On the contributing role of the transmembrane domain for subunit-specific
      sensitivity of integrin activation.
AB  - Integrins are alpha/beta heterodimeric transmembrane adhesion receptors. Evidence
      exists that their transmembrane domain (TMD) separates upon activation. Subunit
      specific differences in activation sensitivity of integrins were reported.
      However, whether sequence variations in the TMD lead to differential TMD
      association has remained elusive. Here, we show by molecular dynamics simulations
      and association free energy calculations on TMDs of integrin alphaIIbbeta3,
      alphavbeta3, and alpha5beta1 that alphaIIbbeta3 TMD is most stably associated;
      this difference is related to interaction differences across the TMDs. The order
      of TMD association stability is paralleled by the basal activity of these
      integrins, which suggests that TMD differences can have a decisive effect on
      integrin conformational free energies. We also identified a specific order of
      clasp disintegration upon TMD dissociation, which suggests that the closed state
      of integrins may comprise several microstates. Our results provide unprecedented
      insights into a possibly contributing role of TMD towards subunit-specific
      sensitivity of integrin activation.

PMID- 29636501
TI  - Analysis of HIV-1 envelope evolution suggests antibody-mediated selection of
      common epitopes among Chinese former plasma donors from a narrow-source outbreak.
AB  - The HIV-1 envelope mutates rapidly to evade recognition and killing, and is a
      major target of humoral immune responses and vaccine development. Identification
      of common epitopes for vaccine development have been complicated by genetic
      variation on both virus and host levels. We studied HIV-1 envelope gp120
      evolution in 12 Chinese former plasma donors infected with a purportedly single
      founder virus, with the aim of identifying common antibody epitopes under immune
      selection. We found five amino acid sites under significant positive selection in
      >=50% of the study participants, and 22 sites consistent with antibody-mediated
      selection. Despite strong selection pressure, some sites housed a limited
      repertoire of amino acids. Structural modelling revealed that most of the
      variable amino acid sites were located on the exposed distal edge of the Gp120
      trimer, whilst invariant sites clustered within the centre of the protein
      complex. Two sites, flanking the V3 hypervariable loop, represent novel antibody
      sites. Analysis of HIV-1 evolution in hosts infected with a narrow-source virus
      may provide insight and novel understanding of common epitopes under antibody
      mediated selection. If verified in functional studies, such epitopes could be
      suitable as targets in vaccine development.

PMID- 29636502
TI  - ACTH and PMX53 recover synaptic transcriptome alterations in a rat model of
      infantile spasms.
AB  - We profiled the gene expression in the hypothalamic arcuate nuclei (ARC) of 20
      male and 20 female rats to determine the infantile spasms (IS) related
      transcriptomic alteration of neurotransmission and recovery following two
      treatments. Rats were prenatally exposed to betamethasone or saline followed by
      repeated postnatal subjection to NMDA-triggered IS. Rats with spasms were treated
      with ACTH, PMX53 or saline. Since ACTH, the first line treatment for IS, has
      inconsistent efficacy and potential harsh side effects, PMX53, a potent
      complement C5ar1 antagonist, was suggested as a therapeutic alternative given its
      effects in other epilepsy models. Novel measures that consider all genes and are
      not affected by arbitrary cut-offs were used, in addition to standard statistical
      tests, to quantify regulation and recovery of glutamatergic, GABAergic,
      cholinergic, dopaminergic and serotonergic pathways. Although IS alters
      expression of ~30% of the ARC genes in both sexes the transcriptomic effects are
      3* more severe in males than their female counterparts, as indicated by the
      Weighted Pathway Regulation measure. Both treatments significantly restored the
      ARC neurotransmission transcriptome to the non-IS condition with PMX53 performing
      slightly better, as measured by the Pathway Restoration Efficiency, suggesting
      these treatments may reduce autistic traits often associated with IS.

PMID- 29636503
TI  - Proteomic approach to understand the molecular physiology of symbiotic
      interaction between Piriformospora indica and Brassica napus.
AB  - Many studies have been now focused on the promising approach of fungal endophytes
      to protect the plant from nutrient deficiency and environmental stresses along
      with better development and productivity. Quantitative and qualitative protein
      characteristics are regulated at genomic, transcriptomic, and posttranscriptional
      levels. Here, we used integrated in-depth proteome analyses to characterize the
      relationship between endophyte Piriformospora indica and Brassica napus plant
      highlighting its potential involvement in symbiosis and overall growth and
      development of the plant. An LC-MS/MS based label-free quantitative technique was
      used to evaluate the differential proteomics under P. indica treatment vs.
      control plants. In this study, 8,123 proteins were assessed, of which 46 showed
      significant abundance (34 downregulated and 12 upregulated) under high confidence
      conditions (p-value <= 0.05, fold change >=2, confidence level 95%). Mapping of
      identified differentially expressed proteins with bioinformatics tools such as GO
      and KEGG pathway analysis showed significant enrichment of gene sets involves in
      metabolic processes, symbiotic signaling, stress/defense responses, energy
      production, nutrient acquisition, biosynthesis of essential metabolites. These
      proteins are responsible for root's architectural modification, cell remodeling,
      and cellular homeostasis during the symbiotic growth phase of plant's life. We
      tried to enhance our knowledge that how the biological pathways modulate during
      symbiosis?

PMID- 29636504
TI  - Cycle oxidation behavior and anti-oxidation mechanism of hot-dipped aluminum
      coating on TiBw/Ti6Al4V composites with network microstructure.
AB  - Controlled and compacted TiAl3 coating was successfully fabricated on the network
      structured TiBw/Ti6Al4V composites by hot-dipping aluminum and subsequent
      interdiffusion treatment. The network structure of the composites was inherited
      to the TiAl3 coating, which effectively reduces the thermal stress and avoids the
      cracks appeared in the coating. Moreover, TiB reinforcements could pin the TiAl3
      coating which can effectively improve the bonding strength between the coating
      and composite substrate. The cycle oxidation behavior of the network structured
      coating on 873 K, 973 K and 1073 K for 100 h were investigated. The results
      showed the coating can remarkably improve the high temperature oxidation
      resistance of the TiBw/Ti6Al4V composites. The network structure was also
      inherited to the Al2O3 oxide scale, which effectively decreases the tendency of
      cracking even spalling about the oxide scale. Certainly, no crack was observed in
      the coating after long-term oxidation due to the division effect of network
      structured coating and pinning effect of TiB reinforcements. Interfacial reaction
      between the coating and the composite substrate occurred and a bilayer structure
      of TiAl/TiAl2 formed next to the substrate after oxidation at 973 K and 1073 K.
      The anti-oxidation mechanism of the network structured coating was also
      discussed.

PMID- 29636505
TI  - A Multi-Parameter Analysis of Cellular Coordination of Major Transcriptome
      Regulation Mechanisms.
AB  - To understand cellular coordination of multiple transcriptome regulation
      mechanisms, we simultaneously measured transcription rate (TR), mRNA abundance
      (RA) and translation activity (TA). This revealed multiple insights. First, the
      three parameters displayed systematic statistical differences. Sequentially more
      genes exhibited extreme (low or high) expression values from TR to RA, and then
      to TA; that is, cellular coordination of multiple transcriptome regulatory
      mechanisms leads to sequentially enhanced gene expression selectivity as the
      genetic information flow from the genome to the proteome. Second, contribution of
      the stabilization-by-translation regulatory mechanism to the cellular
      coordination process was assessed. The data enabled an estimation of mRNA
      stability, revealing a moderate but significant positive correlation between mRNA
      stability and translation activity. Third, the proportion of mRNA occupied by un
      translated regions (UTR) exhibited a negative relationship with the level of this
      correlation, and was thus a major determinant of the mode of regulation of the
      mRNA. High-UTR-proportion mRNAs tend to defy the stabilization-by-translation
      regulatory mechanism, staying out of the polysome but remaining stable; mRNAs
      with little UTRs largely followed this regulation. In summary, we quantitatively
      delineated the relationship among multiple transcriptome regulation parameters,
      i.e., cellular coordination of corresponding regulatory mechanisms.

PMID- 29636507
TI  - Using nested discretization for a detailed yet computationally efficient
      simulation of local hydrology in a distributed hydrologic model.
AB  - Fully distributed hydrologic models are often used to simulate hydrologic states
      at fine spatio-temporal resolutions. However, simulations based on these models
      may become computationally expensive, constraining their applications to smaller
      domains. This study demonstrates that a nested-discretization based modeling
      strategy can be used to improve the efficiency of distributed hydrologic
      simulations, especially for applications where fine resolution estimates of
      hydrologic states are of the focus only within a part of a watershed. To this
      end, we consider two applications where the goal is to capture the groundwater
      dynamics within a defined target area. Our results show that at the target
      locations, a nested simulation is able to competently replicate the estimates of
      groundwater table as obtained from the fine simulation, while yielding
      significant computational savings. The results highlight the potential of using
      nested discretization for a detailed yet computationally efficient estimation of
      hydrologic states in part of the model domain.

PMID- 29636506
TI  - Meta-scale mountain grassland observatories uncover commonalities as well as
      specific interactions among plant and non-rhizosphere soil bacterial communities.
AB  - Interactions between plants and bacteria in the non-rhizosphere soil are rarely
      assessed, because they are less direct and easily masked by confounding
      environmental factors. By studying plant vegetation alliances and soil bacterial
      community co-patterning in grassland soils in 100 sites across a heterogeneous
      mountain landscape in the western Swiss Alps, we obtained sufficient statistical
      power to disentangle common co-occurrences and weaker specific interactions.
      Plant alliances and soil bacterial communities tended to be synchronized in
      community turnover across the landscape, largely driven by common underlying
      environmental factors, such as soil pH or elevation. Certain alliances occurring
      in distinct, local, environmental conditions were characterized by co-occurring
      specialist plant and bacterial species, such as the Nardus stricta and
      Thermogemmatisporaceae. In contrast, some generalist taxa, like Anthoxanthum
      odoratum and 19 Acidobacteria species, spanned across multiple vegetation
      alliances. Meta-scale analyses of soil bacterial community composition and
      vegetation surveys, complemented with local edaphic measurements, can thus prove
      useful to identify the various types of plant-bacteria interactions and the
      environments in which they occur.

PMID- 29636508
TI  - Enrichment of soil organic carbon by native earthworms in a patch of tropical
      soil, Kerala, India: First report.
AB  - The role of earthworms in soil carbon dynamics is a recent avenue of research
      which is less studied in India. Three plots of 1 m3 size were laid in Jeevaka
      live laboratory (JLL)- a biodiversity rich area within the University campus. A
      control plot (CP) of same dimension was maintained outside JLL. Out of three
      plots within JLL, one was operated with native earthworm Perionyx
      ceylanensisMichaelson (100 numbers), water and cattle dung as feed (Jeevaka test
      plot- JT) and fenced with nylon mesh. Remaining two plots were operated as
      controls within JLL (JC1 and JC2). JC1 (Jeevaka control 1) was provided with
      cattle dung and water, while JC2 and CP (outside JLL) were operated without any
      supplements. Throughout the experiment native earthworm species have maintained
      their dominancy in all plots except CP where no earthworms were observed. At the
      end of a year-long study, JC1 with maximum diversity of earthworms showed better
      soil organic carbon (SOC) and particulate organic carbon (POC)-which is
      relatively a stable form of SOC. Overall findings indicate better the diversity
      of earthworms better is the carbon storage in the soil.

PMID- 29636509
TI  - Matriptase-2 deficiency protects from obesity by modulating iron homeostasis.
AB  - Alterations in iron status have frequently been associated with obesity and other
      metabolic disorders. The hormone hepcidin stands out as a key regulator in the
      maintenance of iron homeostasis by controlling the main iron exporter,
      ferroportin. Here we demonstrate that the deficiency in the hepcidin repressor
      matriptase-2 (Tmprss6) protects from high-fat diet-induced obesity. Tmprss6 -/-
      mice show a significant decrease in body fat, improved glucose tolerance and
      insulin sensitivity, and are protected against hepatic steatosis. Moreover, these
      mice exhibit a significant increase in fat lipolysis, consistent with their
      dramatic reduction in adiposity. Rescue experiments that block hepcidin up
      regulation and restore iron levels in Tmprss6-/- mice via anti-hemojuvelin (HJV)
      therapy, revert the obesity-resistant phenotype of Tmprss6-/- mice. Overall, this
      study describes a role for matritpase-2 and hepcidin in obesity and highlights
      the relevance of iron regulation in the control of adipose tissue function.

PMID- 29636510
TI  - Plasmodium falciparum strains spontaneously switch invasion phenotype in
      suspension culture.
AB  - The extensive redundancy in the use of invasion ligands by Plasmodium falciparum,
      and its unique ability to switch between invasion pathways have hampered vaccine
      development. P. falciparum strains Dd2 and W2mef have been shown to change from
      sialic acid (SA)-dependent to SA-independent phenotypes when selected on
      neuraminidase-treated erythrocytes. Following an observation of increasing
      ability of Dd2 to invade neuraminidase-treated cells when cultured for several
      weeks, we systematically investigated this phenomenon by comparing invasion
      phenotypes of Dd2, W2mef and 3D7 strains of P. falciparum that were cultured with
      gentle shaking (Suspended) or under static (Static) conditions. While Static Dd2
      and W2mef remained SA-dependent for the entire duration of the investigation,
      Suspended parasites spontaneously and progressively switched to SA-independent
      phenotype from week 2 onwards. Furthermore, returning Suspended cultures to
      Static conditions led to a gradual reversal to SA-dependent phenotype. The switch
      to SA-independent phenotype was accompanied by upregulation of the key invasion
      ligand, reticulocyte-binding homologue 4 (RH4), and the increased invasion was
      inhibited by antibodies to the RH4 receptor, CR1. Our data demonstrates a novel
      mechanism for inducing the switching of invasion pathways in P. falciparum
      parasites and may provide clues for understanding the mechanisms involved.

PMID- 29636511
TI  - Regimes of Flow over Complex Structures of Endothelial Glycocalyx: A Molecular
      Dynamics Simulation Study.
AB  - Flow patterns on surfaces grafted with complex structures play a pivotal role in
      many engineering and biomedical applications. In this research, large-scale
      molecular dynamics (MD) simulations are conducted to study the flow over complex
      surface structures of an endothelial glycocalyx layer. A detailed structure of
      glycocalyx has been adopted and the flow/glycocalyx system comprises about
      5,800,000 atoms. Four cases involving varying external forces and modified
      glycocalyx configurations are constructed to reveal intricate fluid behaviour.
      Flow profiles including temporal evolutions and spatial distributions of velocity
      are illustrated. Moreover, streamline length and vorticity distributions under
      the four scenarios are compared and discussed to elucidate the effects of
      external forces and glycocalyx configurations on flow patterns. Results show that
      sugar chain configurations affect streamline length distributions but their
      impact on vorticity distributions is statistically insignificant, whilst the
      influence of the external forces on both streamline length and vorticity
      distributions are trivial. Finally, a regime diagram for flow over complex
      surface structures is proposed to categorise flow patterns.

PMID- 29636512
TI  - A large-scale survey of the postmortem human microbiome, and its potential to
      provide insight into the living health condition.
AB  - The microbiome plays many roles in human health, often through the exclusive lens
      of clinical interest. The inevitable end point for all living hosts, death, has
      its own altered microbiome configurations. However, little is understood about
      the ecology and changes of microbial communities after death, or their potential
      utility for understanding the health condition of the recently living. Here we
      reveal distinct postmortem microbiomes of human hosts from a large-scale survey
      of death cases representing a predominantly urban population, and demonstrated
      these microbiomes reflected antemortem health conditions within 24-48 hours of
      death. Our results characterized microbial community structure and predicted
      function from 188 cases representing a cross-section of an industrial-urban
      population. We found strong niche differentiation of anatomic habitat and
      microbial community turnover based on topographical distribution. Microbial
      community stability was documented up to two days after death. Additionally, we
      observed a positive relationship between cell motility and time since host death.
      Interestingly, we discovered evidence that microbial biodiversity is a predictor
      of antemortem host health condition (e.g., heart disease). These findings improve
      the understanding of postmortem host microbiota dynamics, and provide a robust
      dataset to test the postmortem microbiome as a tool for assessing health
      conditions in living populations.

PMID- 29636513
TI  - Imaging beyond ultrasonically-impenetrable objects.
AB  - Ultrasound images are severely degraded by the presence of obstacles such as
      bones and air gaps along the beam path. This paper describes a method for imaging
      structures that are distal to obstacles that are otherwise impenetrable to
      ultrasound. The method uses an optically-inspired holographic algorithm to beam
      shape the emitted ultrasound field in order to bypass the obstacle and place the
      beam focus beyond the obstruction. The resulting performance depends on the
      transducer aperture, the size and position of the obstacle, and the position of
      the target. Improvement compared to standard ultrasound imaging is significant
      for obstacles for which the width is larger than one fourth of the transducer
      aperture and the depth is within a few centimeters of the transducer. For such
      cases, the improvement in focal intensity at the location of the target reaches
      30-fold, and the improvement in peak-to-side-lobe ratio reaches 3-fold. The
      method can be implemented in conventional ultrasound systems, and the entire
      process can be performed in real time. This method has applications in the fields
      of cancer detection, abdominal imaging, imaging of vertebral structure and
      ultrasound tomography. Here, its effectiveness is demonstrated using wire
      targets, tissue mimicking phantoms and an ex vivo biological sample.

PMID- 29636514
TI  - Prediction of spacer-alpha6 complex: a novel insight into binding of ADAMTS13
      with A2 domain of von Willebrand factor under forces.
AB  - Force-regulated cleavage of A2 domain of von Willebrand factor (vWF) by ADAMTS13
      is a key event in preventing thrombotic thrombocytopenic purpura (TTP).
      Recognition and cleavage depend on cooperative and modular contacts between
      several ADAMTS13 subdomains and discrete segments of vWF A2 domain. Spacer domain
      of ADAMTS13 contains an important exosite interacting with alpha6 helix of unfold
      A2 domain, but it remains unclear whether stretching of alpha6 regulates binding
      to spacer. To understand the molecular mechanism underlying the interactions
      between spacer and alpha6 under stretching, we successfully predicted spacer
      alpha6 complex by a novel computer strategy combined the steered molecular
      dynamics (SMD) and flexible docking techniques. This strategy included three
      steps: (1) constant-velocity SMD simulation of alpha6; (2) zero-velocity SMD
      simulations of alpha6, and (3) flexible dockings of alpha6 to spacer. In our
      spacer-alpha6 complex model, 13 key residues, six in alpha6 and seven in spacer,
      were identified. Our data demonstrated a biphasic extension-regulated binding of
      alpha6 to spacer. The binding strength of the complex increased with alpha6
      extension until it reaches its optimum of 0.25 nm, and then decreased as alpha6
      extension further increased, meaning that spacer is in favor to binding with a
      partially extended alpha6, which may contribute to the optimal contact and
      proteolysis. Changes of interface area and intermolecular salt bridge may serve
      as the molecular basis for this characteristic. These findings provide a novel
      insight into mechano-chemical regulation on interaction between ADAMTS13 and vWF
      A2 domain under forces.

PMID- 29636515
TI  - Impact of Bimaxillary Advancement Surgery on the Upper Airway and on Obstructive
      Sleep Apnea Syndrome: a Meta-Analysis.
AB  - Upper airway changes following bimaxillary advancement surgery to treat
      obstructive sleep apnea syndrome remain controversial. The main objective of this
      systematic review and meta-analysis was to investigate the effects of bimaxillary
      advancement surgery on the upper airway (UA) of obstructive sleep apnea syndrome
      patients through examining changes three-dimensionally in vertical and supine
      position and through changes in oximetric variables (AHI, RDI, O2 Sat) and in the
      quality of life measured by the Epworth sleepiness scale (ESS). A thorough search
      of the PubMed, Scopus, Embase and Cochrane databases and a grey literature search
      (Opengrey) were conducted. No limit was placed on publication year or language.
      The inclusion criteria were: adult obstructive sleep apnea patients who had
      undergone bimaxillary advancement surgery, three-dimensional CBCT or CT and
      oximetric measurements and at least six weeks follow-up. Sample sizes of under 10
      patients were excluded. Finally, 26 articles were included in the qualitative
      review and 23 in the meta-analysis. Bimaxillary advancement surgery has been
      shown to be beneficial in terms of increased upper airway size, improved
      oximetric indicators and the quality of life measured on the Epworth sleepiness
      scale.

PMID- 29636516
TI  - Testing the impact of effective population size on speciation rates - a negative
      correlation or lack thereof in lichenized fungi.
AB  - The effect of microevolutionary processes on macroevolutionary patterns, and vice
      versa, is an important but under-investigated question. Here we present an
      integrative population genetic and phylogenetic study using molecular sequence
      data from three lichen-forming fungal lineages to empirically test the potential
      correlation between effective population size - approximated by the parameter
      theta - and estimated speciation rates using a phylogenetic tree (lambda). A
      negative association between theta and lambda was supported in one lineage of
      lichen-forming fungi, Melanelixia (Parmeliaceae), while no significant
      relationships was found for two other genera within the same family, Melanohalea
      and Xanthoparmelia. We discuss the significance of our results and the importance
      of considering microevolutionary processes when studying macroevolutionary
      patterns.

PMID- 29636517
TI  - Application of iron-loaded activated carbon electrodes for electrokinetic
      remediation of chromium-contaminated soil in a three-dimensional electrode
      system.
AB  - Hexavalent chromium from industrial residues is highly mobile in soil and can
      lead to the contamination of groundwater through runoff and leaching after
      rainfall. This paper focuses on the three-dimensional (3D) electrokinetic
      remediation (EKR) of chromium-contaminated soil from an industrial site.
      Activated carbon particles coupled with Fe ions (AC-Fe) were used as the third
      electrode. The optimum dose ratio of the electrode particles and remediation time
      were selected on the basis of single-factor experiments. X-ray photoelectron
      spectroscopy (XPS) analysis was carried out to explore the reduction of Cr(VI) on
      the surface of the electrode particles (AC-Fe). The results showed that AC-Fe had
      a positive effect on Cr(VI) reduction with a removal rate of 80.2%, which was
      achieved after 10 d by using a 5% dose of electrode particles. Finally, it was
      concluded that the removal mechanism combined the processes of electromigration,
      electrosorption/adsorption and reduction of Cr(VI) in the 3D EKR system.

PMID- 29636518
TI  - Association between fasting Triglyceride levels and the Prevalence of
      Asymptomatic Intracranial Arterial Stenosis in a Chinese Community-based Study.
AB  - The aim of this study was to assess the association between fasting triglyceride
      (FTG) levels and the prevalence of asymptomatic intracranial arterial stenosis
      (ICAS). The Asymptomatic Polyvascular Abnormalities Community (APAC) study is a
      sub-population of the Kailuan study which targeting on the epidemiology of
      asymptomatic polyvascular abnormalities in Chinese adults. A total number of 5345
      participants, aged >=40, and without history of stroke, transient ischemic
      attack, and coronary heart disease were enrolled in this study. Transcranial
      Doppler Ultrasonography was performed for the detection of ICAS presence. Out of
      5345 participants, 698 subjects diagnosed ICAS (13.1%). In univariate analysis,
      the association between fasting TG (FTG) levels and asymptomatic ICAS didn't
      reach statistical significance (OR: 0.99, 95% CI: 0.89-1.09; P = 0.79), the same
      conclusion was reached in multivariate analysis, after adjustment for age, sex
      (OR: 1.05, 95% CI: 0.95-1.17) and age, sex, current smoking status, hypertension,
      diabetes, body mass index, estimated glomerular filtration rate, total
      cholesterol, high-density lipoprotein cholesterol and low-density lipoprotein
      cholesterol (OR: 0.95, 95% CI: 0.84-1.06), respectively. FTG failed to show any
      statistical significance on ICAS presence in the APAC study, but the TG actually
      plays an important role in the progression of atherosclerosis as a biomarker.

PMID- 29636519
TI  - Synthesis of Au@polymer nanohybrids with transited core-shell morphology from
      concentric to eccentric Emoji-N or Janus nanoparticles.
AB  - The combination of multifunctionality and synergestic effect displayed by hybrid
      nanoparticles (NPs) has been revealed as an effective stratagem in the
      development of advanced nanostructures with unique biotechnology and
      optoelectronic applications. Although important work has been devoted, the demand
      of facile, versatile and efficient synthetic approach remains still challenging.
      Herein, we report a feasible and innovative way for polymer-shell assembling onto
      gold nanoparticles in competitive conditions of hydrophobic/hydrophilic feature
      and interfacial energy of components to generate core-shell nanohybrids with
      singular morphologies. The fine control of reaction parameters allows a modulated
      transformation from concentric to eccentric nanostructure-geometries. In this
      regard, a rational selection of the components and solvent ratio guarantee the
      reproducibility and efficiency on hybrid-nanoassembly. Furthermore, the
      simplicity of the synthetic approach offers the possibility to obtain asymmetric
      Janus NPs and new morphologies (quizzical-aspheric polymer-shell, named Emoji-N
      hybrids) with adjustable surface-coating, leading to new properties and
      applications that are unavailable to their symmetrical or single components.

PMID- 29636520
TI  - GC-MS-based urinary organic acid profiling reveals multiple dysregulated
      metabolic pathways following experimental acute alcohol consumption.
AB  - Metabolomics studies of diseases associated with chronic alcohol consumption
      provide compelling evidence of several perturbed metabolic pathways. Moreover,
      the holistic approach of such studies gives insights into the pathophysiological
      risk factors associated with chronic alcohol-induced disability, morbidity and
      mortality. Here, we report on a GC-MS-based organic acid profiling study on acute
      alcohol consumption. Our investigation - involving 12 healthy, moderate-drinking
      young men - simulated a single binge drinking event, and indicated its metabolic
      consequences. We generated time-dependent data that predicted the metabolic
      pathophysiology of the alcohol intervention. Multivariate statistical modelling
      was applied to the longitudinal data of 120 biologically relevant organic acids,
      of which 13 provided statistical evidence of the alcohol effect. The known
      alcohol-induced increased NADH:NAD+ ratio in the cytosol of hepatocytes
      contributed to the global dysregulation of several metabolic reactions of
      glycolysis, ketogenesis, the Krebs cycle and gluconeogenesis. The significant
      presence of 2-hydroxyisobutyric acid supports the emerging paradigm that this
      compound is an important endogenous metabolite. Its metabolic origin remains
      elusive, but recent evidence indicated 2-hydroxyisobutyrylation as a novel
      regulatory modifier of histones. Metabolomics has thus opened an avenue for
      further research on the reprogramming of metabolic pathways and epigenetic
      networks in relation to the severe effects of alcohol consumption.

PMID- 29636521
TI  - Exploration of the effect of sequence variations located inside the binding
      pocket of HIV-1 and HIV-2 proteases.
AB  - HIV-2 protease (PR2) is naturally resistant to most FDA (Food and Drug
      Administration)-approved HIV-1 protease inhibitors (PIs), a major antiretroviral
      class. In this study, we compared the PR1 and PR2 binding pockets extracted from
      structures complexed with 12 ligands. The comparison of PR1 and PR2 pocket
      properties showed that bound PR2 pockets were more hydrophobic with more oxygen
      atoms and fewer nitrogen atoms than PR1 pockets. The structural comparison of PR1
      and PR2 pockets highlighted structural changes induced by their sequence
      variations and that were consistent with these property changes. Specifically,
      substitutions at residues 31, 46, and 82 induced structural changes in their main
      chain atoms that could affect PI binding in PR2. In addition, the modelling of
      PR1 mutant structures containing V32I and L76M substitutions revealed a
      cooperative mechanism leading to structural deformation of flap-residue 45 that
      could modify PR2 flexibility. Our results suggest that substitutions in the PR1
      and PR2 pockets can modify PI binding and flap flexibility, which could underlie
      PR2 resistance against PIs. These results provide new insights concerning the
      structural changes induced by PR1 and PR2 pocket variation changes, improving the
      understanding of the atomic mechanism of PR2 resistance to PIs.

PMID- 29636522
TI  - Satiation state-dependent dopaminergic control of foraging in Drosophila.
AB  - Hunger evokes stereotypic behaviors that favor the discovery of nutrients. The
      neural pathways that coordinate internal and external cues to motivate foraging
      behaviors are only partly known. Drosophila that are food deprived increase
      locomotor activity, are more efficient in locating a discrete source of
      nutrition, and are willing to overcome adversity to obtain food. We developed a
      simple open field assay that allows flies to freely perform multiple steps of the
      foraging sequence, and we show that two distinct dopaminergic neural circuits
      regulate measures of foraging behaviors. One group, the PAM neurons, functions in
      food deprived flies while the other functions in well fed flies, and both promote
      foraging. These satiation state-dependent circuits converge on dopamine D1
      receptor-expressing Kenyon cells of the mushroom body, where neural activity
      promotes foraging independent of satiation state. These findings provide evidence
      for active foraging in well-fed flies that is separable from hunger-driven
      foraging.

PMID- 29636523
TI  - Gestational exposure to metformin programs improved glucose tolerance and insulin
      secretion in adult male mouse offspring.
AB  - Pancreatic beta-cells are exquisitely sensitive to developmental nutrient
      stressors, and alterations in nutrient sensing pathways may underlie changes
      observed in these models. Here we developed a mouse model of in utero exposure to
      the anti-diabetic agent metformin. We have previously shown that this exposure
      increases offspring pancreatic beta-cell mass at birth. We hypothesized that
      adult offspring would have improved metabolic parameters as a long-term outcome
      of metformin exposure. Virgin dams were given 5 mg/mL metformin in their water
      from E0.5 to delivery at E18.5. Body weight, glucose tolerance, insulin tolerance
      and glucose stimulated insulin secretion were analyzed in the offspring. When
      male offspring of dams given metformin during gestation were tested as adults
      they had improved glucose tolerance and enhanced insulin secretion in vivo as did
      their islets in vitro. Enhanced insulin secretion was accompanied by changes in
      intracellular free calcium responses to glucose and potassium chloride, possibly
      mediated by increased L channel expression. Female offspring exhibited improved
      glucose tolerance at advanced ages. In conclusion, in this model in utero
      metformin exposure leads to improved offspring metabolism in a gender-specific
      manner. These findings suggest that metformin applied during gestation may be an
      option for reprogramming metabolism in at risk groups.

PMID- 29636525
TI  - Study of mucin turnover in the small intestine by in vivo labeling.
AB  - Mucins are highly glycosylated proteins which protect the epithelium. In the
      small intestine, the goblet cell-secreted Muc2 mucin constitutes the main
      component of the loose mucus layer that traps luminal material. The transmembrane
      mucin Muc17 forms part of the carbohydrate-rich glycocalyx covering intestinal
      epithelial cells. Our study aimed at investigating the turnover of these mucins
      in the small intestine by using in vivo labeling of O-glycans with N
      azidoacetylgalactosamine. Mice were injected intraperitoneally and sacrificed
      every hour up to 12 hours and at 24 hours. Samples were fixed with preservation
      of the mucus layer and stained for Muc2 and Muc17. Turnover of Muc2 was slower in
      goblet cells of the crypts compared to goblet cells along the villi. Muc17 showed
      stable expression over time at the plasma membrane on villi tips, in crypts and
      at crypt openings. In conclusion, we have identified different subtypes of goblet
      cells based on their rate of mucin biosynthesis and secretion. In order to
      protect the intestinal epithelium from chemical and bacterial hazards, fast and
      frequent renewal of the secreted mucus layer in the villi area is combined with
      massive secretion of stored Muc2 from goblet cells in the upper crypt.

PMID- 29636524
TI  - DNA-release by Streptococcus pneumoniae autolysin LytA induced Krueppel-like
      factor 4 expression in macrophages.
AB  - The recruitment of myeloid cells to the lung is of utmost importance for the
      elimination of invading pathogens. We investigated the Streptococcus pneumoniae
      dependent induction mechanism of KLF4 in macrophages as a potential regulator of
      the macrophage immune response. We demonstrated that only viable pneumococci,
      which have direct contact to the host cells and release LytA-dependent DNA,
      induced KLF4. Exogenous supplementation of pneumococcal, other bacterial,
      eukaryotic foreign (human) or self (mouse) DNA to autolysis-deficient pneumococci
      restored (at least in part) pneumococci-related KLF4 induction. Experiments using
      TLR9, TRIF and MyD88 knockout macrophages revealed that TLR9, TRIF and MyD88 were
      partly involved in the S. pneumoniae-induced KLF4 expression. BMMs missing
      important DNA receptor related molecules (ASC-/-, STING-/-) showed no differences
      in pneumococci-related KLF4 expression. Similar results were observed with IFNAR
      /- BMMs and Type I IFN stimulated cells. LyzMcre mediated knockdown of KLF4 in
      BMMs resulted in a decreased secretion of proinflammatory cytokines and enhanced
      IL-10 release. In summary, we showed that pneumococci-related KLF4 induction in
      macrophages is mediated via a PAMP-DAMP induction mechanism involving a hitherto
      unknown host cell DNA sensor leading to a more proinflammatory macrophage
      phenotype.

PMID- 29636526
TI  - Author Correction: Mother's Pre-pregnancy BMI and Placental Candidate miRNAs:
      Findings from the ENVIRONAGE Birth Cohort.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 29636527
TI  - GADD45A and CDKN1A are involved in apoptosis and cell cycle modulatory effects of
      viscumTT with further inactivation of the STAT3 pathway.
AB  - ViscumTT, a whole mistletoe preparation, has shown synergistic induction of
      apoptosis in several pediatric tumor entities. High therapeutic potential has
      previously been observed in Ewing's sarcoma, rhabdomyosarcoma, ALL and AML. In
      this study, we analyzed modulatory effects on the cell cycle by viscumTT in three
      osteosarcoma cell lines with various TP53 statuses. ViscumTT treatment induced G1
      arrest in TP53 wild-type and null-mutant cells, but S arrest in TP53 mutant
      cells. Blockage of G1/S transition was accompanied by down-regulation of the key
      regulators CDK4, CCND1, CDK2, CCNE, CCNA. However, investigations on the
      transcriptional level revealed secondary TP53 participation. Cell cycle arrest
      was predominantly mediated by transcriptionally increased expression of GADD45A
      and CDKN1A and decreased SKP2 levels. Enhanced CDKN1A and GADD45A expression
      further played a role in viscumTT-induced apoptosis with involvement of stress
      induced MAPK8 and inactivation of MAPK1/3. Furthermore, viscumTT inhibited the
      pro-survival pathway STAT3 by dephosphorylation of the two sites, Tyr705 and
      Ser727, by down-regulation of total STAT3 and its direct downstream targets BIRC5
      and C-MYC. Moreover, tests of the efficacy of viscumTT in vivo showing reduction
      of tumor volume confirmed the high therapeutic potential as an anti-tumoral agent
      for osteosarcoma.

PMID- 29636528
TI  - Inhibition of homoserine dehydrogenase by formation of a cysteine-NAD covalent
      complex.
AB  - Homoserine dehydrogenase (EC 1.1.1.3, HSD) is an important regulatory enzyme in
      the aspartate pathway, which mediates synthesis of methionine, threonine and
      isoleucine from aspartate. Here, HSD from the hyperthermophilic archaeon
      Sulfolobus tokodaii (StHSD) was found to be inhibited by cysteine, which acted as
      a competitive inhibitor of homoserine with a Ki of 11 MUM and uncompetitive an
      inhibitor of NAD and NADP with Ki's of 0.55 and 1.2 mM, respectively. Initial
      velocity and product (NADH) inhibition analyses of homoserine oxidation indicated
      that StHSD first binds NAD and then homoserine through a sequentially ordered
      mechanism. This suggests that feedback inhibition of StHSD by cysteine occurs
      through the formation of an enzyme-NAD-cysteine complex. Structural analysis of
      StHSD complexed with cysteine and NAD revealed that cysteine situates within the
      homoserine binding site. The distance between the sulfur atom of cysteine and the
      C4 atom of the nicotinamide ring was approximately 1.9 A, close enough to form a
      covalent bond. The UV absorption-difference spectrum of StHSD with and without
      cysteine in the presence of NAD, exhibited a peak at 325 nm, which also suggests
      formation of a covalent bond between cysteine and the nicotinamide ring.

PMID- 29636529
TI  - Loss of MeCP2 in adult 5-HT neurons induces 5-HT1A autoreceptors, with opposite
      sex-dependent anxiety and depression phenotypes.
AB  - The 5-HT1A autoreceptor mediates feedback inhibition of serotonin (5-HT) neurons,
      and is implicated in major depression. The human 5-HT1A gene (HTR1A) rs6295 risk
      allele prevents Deaf1 binding to HTR1A, resulting in increased 5-HT1A
      autoreceptor transcription. Since chronic stress alters HTR1A methylation and
      expression, we addressed whether recruitment of methyl-binding protein MeCP2 may
      alter Deaf1 regulation at the HTR1A locus. We show that MeCP2 enhances Deaf1
      binding to its HTR1A site and co-immunoprecipitates with Deaf1 in cells and brain
      tissue. Chromatin immunoprecipitation assays showed Deaf1-dependent recruitment
      of MeCP2 to the mouse HTR1A promoter, and MeCP2 modulated human and mouse HTR1A
      gene transcription in a Deaf1-dependent fashion, enhancing Deaf1-induced
      repression at the Deaf1 site. To address the role of MeCP2 in HTR1A regulation in
      vivo, mice with conditional knockout of MeCP2 in adult 5-HT neurons (MeCP2 cKO)
      were generated. These mice exhibited increased 5-HT1A autoreceptor levels and
      function, consistent with MeCP2 enhancement of Deaf1 repression in 5-HT neurons.
      Interestingly, female MeCP2-cKO mice displayed reduced anxiety, while males
      showed increased anxiety and reduced depression-like behaviors. These data
      uncover a novel role for MeCP2 in 5-HT neurons to repress HTR1A expression and
      drive adult anxiety- and depression-like behaviors in a sex-specific manner.

PMID- 29636530
TI  - Rapid isolation and enrichment of extracellular vesicle preparations using anion
      exchange chromatography.
AB  - Extracellular vesicles (EVs) have important roles in physiology, pathology, and
      more recently have been identified as efficient carriers of therapeutic cargoes.
      For efficient study of EVs, a single-step, rapid and scalable isolation strategy
      is necessary. Chromatography techniques are widely used for isolation of
      biological material for clinical applications and as EVs have a net negative
      charge, anion exchange chromatography (AIEX) is a strong candidate for column
      based EV isolation. We isolated EVs by AIEX and compared them to EVs isolated by
      ultracentrifugation (UC) and tangential flow filtration (TFF). EVs isolated by
      AIEX had comparable yield, EV marker presence, size and morphology to those
      isolated by UC and had decreased protein and debris contamination as compared to
      TFF purified EVs. An improved AIEX protocol allowing for higher flow rates and
      step elution isolated 2.4*1011 EVs from 1 litre of cell culture supernatant
      within 3 hours and removed multiple contaminating proteins. Importantly AIEX
      isolated EVs from different cell lines including HEK293T, H1299, HCT116 and
      Expi293F cells. The AIEX protocol described here can be used to isolate and
      enrich intact EVs in a rapid and scalable manner and shows great promise for
      further use in the field for both research and clinical purposes.

PMID- 29636531
TI  - Low-dose tributyltin exposure induces an oxidative stress-triggered JNK-related
      pancreatic beta-cell apoptosis and a reversible hypoinsulinemic hyperglycemia in
      mice.
AB  - Tributyltin (TBT), an endocrine disrupting chemical, can be found in food
      (particular in fish and seafood) and drinking water by contamination. Here, we
      elucidated the effects and possible mechanisms of low-dose TBT on the growth and
      function of pancreatic beta-cells and glucose metabolism in mice. Submicromolar
      concentration of TBT significantly induced beta-cell cytotoxicity and apoptosis,
      which were accompanied by poly (ADP-ribose) polymerase cleavage and mitogen
      activated protein kinases-JNK and ERK1/2 phosphorylation. TBT could also suppress
      the glucose-stimulated insulin secretion in beta-cells and isolated mouse islets.
      TBT increased reactive oxygen species production. TBT-induced beta-cell
      cytotoxicity and apoptosis were significantly prevented by antioxidant N
      acetylcysteine (NAC) and JNK inhibitor SP600125, but not ERK1/2 inhibitor PD98059
      and p38 inhibitor SB203580. Both NAC and SP600125 inhibited JNK phosphorylation
      and reduced cell viability in TBT-treated beta-cells. Four-week exposure of TBT
      (0.25 mg/kg) to mice revealed the decreased plasma insulin, increased blood
      glucose and plasma malondialdehyde, suppressed islet insulin secretion, and
      increased islet caspase-3 activity, which could be reversed by NAC treatment.
      After removing the TBT exposure for 2 weeks, the TBT-induced glucose metabolism
      alteration was significantly reversed. These results suggest that low-dose TBT
      can induce beta-cell apoptosis and interfere with glucose homeostasis via an
      oxidative stress-related pathway.

PMID- 29636533
TI  - Reproduction method for dried biomodels composed of poly (vinyl alcohol)
      hydrogels.
AB  - Models mimicking the realistic geometries and mechanical properties of human
      tissue are requiring ever-better materials. Biomodels made of poly (vinyl
      alcohol) are particularly in demand, as they can be used to realistically
      reproduce the characteristics of blood vessels. The reproducibility of biomodels
      can be altered due to dehydration that is observed after long periods of usage.
      In order to improve their usability, one should consider the method used to
      reproduce them; however, few studies have reported a method reproduce biomodels.
      This study proposes a novel reproduction method for biomodels that allows them to
      quickly and easily reproduce their geometric and mechanical properties. Specimens
      of the dried biomodels were reformed through immersion in temperature-controlled
      water. Our results show that water at 35  degrees C can be effective to reproduce
      both the geometric and mechanical properties of the specimens. X-ray diffraction
      (XRD) measurements revealed that water immersion can reform the crystal structure
      of the pre-dried specimens, and images obtained using micro-computed tomography
      acquisition show that the geometry of the specimens can be reformed by water
      immersion without introducing any defects. These results indicate that the
      proposed method can lead to high reproducibility of both the original geometric
      and mechanical properties of the dried biomodels.

PMID- 29636532
TI  - Chronic cigarette smoke exposure drives spiral ganglion neuron loss in mice.
AB  - Tobacco use is associated with an increased risk of hearing loss in older
      individuals, suggesting cigarette smoke (CS) exposure may target the peripheral
      auditory organs. However, the effects of CS exposure on general cochlear anatomy
      have not previously been explored. Here we compare control and chronic CS exposed
      cochleae from adult mice to assess changes in structure and cell survival. Two
      photon imaging techniques, including the imaging of second harmonic generation
      (SHG) and two-photon excitation fluorescence (TPEF) from native molecules, were
      used to probe the whole cochlear organ for changes. We found evidence for
      fibrillar collagen accumulation in the spiral ganglion and organ of Corti,
      consistent with fibrosis. Quantitative TPEF indicated that basal CS-exposed
      spiral ganglion neurons experienced greater oxidative stress than control
      neurons, which was confirmed by histological staining for lipid peroxidation
      products. Cell counts confirmed that the CS-exposed spiral ganglion also
      contained fewer basal neurons. Taken together, these data support the premise
      that CS exposure induces oxidative stress in cochlear cells. They also indicate
      that two-photon techniques may screen cochlear tissues for oxidative stress.

PMID- 29636534
TI  - Visualizing the bidirectional optical transfer function for near-field
      enhancement in waveguide coupled plasmonic transducers.
AB  - We report visualizations of the bidirectional near-field optical transfer
      function for a waveguide-coupled plasmonic transducer as a metrology technique
      essential for successful development for mass-fabricated near-field devices.
      Plasmonic devices have revolutionized the observation of nanoscale phenomena,
      enabling optical excitation and readout from nanoscale regions of fabricated
      devices instead of as limited by optical diffraction. Visualizations of the
      plasmonic transducer modes were acquired both by local near-field excitation of
      the antenna on the front facet of a waveguide using the focused electron beam of
      a scanning electron microscope as a probe of the near-field cathodoluminescence
      during far-field collection from the back facet of the waveguide, and by local
      mapping of the optical near-field for the same antenna design using scattering
      scanning near-field optical microscopy as a probe of the near-field optical mode
      density for far-field light focused into the back facet of the waveguide. Strong
      agreement between both measurement types and numerical modeling was observed,
      indicating that the method enables crucial metrological comparisons of as
      fabricated device performance to as-modeled device expectations for heat-assisted
      magnetic recording heads, which can be extended to successful development of
      future near-field-on-chip devices such as optical processor interconnects.

PMID- 29636536
TI  - It is high time to examine the psyche while treating IBD.

PMID- 29636535
TI  - A clinically relevant and bias-controlled murine model to study acute traumatic
      coagulopathy.
AB  - Acute traumatic coagulopathy (ATC) is an acute and endogenous mechanism triggered
      by the association of trauma and hemorrhage. Several animal models have been
      developed, but some major biases have not yet been identified. Our aim was to
      develop a robust and clinically relevant murine model to study this condition.
      Anesthetized adult Sprague Dawley rats were randomized into 4 groups: C, control;
      T, trauma; H, hemorrhage; TH, trauma and hemorrhage (n = 7 each). Trauma
      consisted of laparotomy associated with four-limb and splenic fractures. Clinical
      variables, ionograms, arterial and hemostasis blood tests were compared at 0 and
      90 min. ATC and un-compensated shock were observed in group TH. In this group,
      the rise in prothrombin time and activated partial thromboplastin was 29 and 40%,
      respectively. Shock markers, compensation mechanisms and coagulation pathways
      were all consistent with human pathophysiology. The absence of confounding
      factors, such as trauma-related bleeding or dilution due to trans-capillary
      refill was verified. This ethic, cost effective and bias-controlled model
      reproduced the specific and endogenous mechanism of ATC and will allow to
      identify potential targets for therapeutics in case of trauma-related hemorrhage.

PMID- 29636537
TI  - Lagged influence of Atlantic and Pacific climate patterns on European extreme
      precipitation.
AB  - The risk of European extreme precipitation and flooding as an economic and
      humanitarian disaster is modulated by large-scale atmospheric processes that
      operate over (multi-)decadal periods and transport huge quantities of moisture
      inland from the oceans. Yet the previous studies for better understanding of
      extreme precipitation variability and its skillful seasonal prediction are far
      from comprehensive. Here we show that the winter North Atlantic Oscillation (NAO)
      and, to a lesser extent, winter ENSO signal have a controlling influence not only
      concurrently on European extreme precipitation anomaly in winter, but in a
      delayed way on the extremes in the following seasons. In a similar pattern, there
      is a strong footprint of summer atmospheric circulations over the Mediterranean
      Sea on summer extreme precipitation and with 1-, 2- and 3-season lags on the
      following autumn, winter and spring extremes. The combined influences of the
      different atmospheric circulation patterns mark a significant step forward for an
      improved predictability of European extreme precipitation in the state-of-the-art
      seasonal prediction systems.

PMID- 29636538
TI  - The gut microbiota influences anticancer immunosurveillance and general health.
AB  - Discoveries made in the past 5 years indicate that the composition of the
      intestinal microbiota has a major influence on the effectiveness of anticancer
      immunosurveillance and thereby contributes to the therapeutic activity of immune
      checkpoint inhibitors that target cytotoxic T lymphocyte protein 4 (CTLA-4) or
      the programmed cell death protein 1 (PD-1)-programmed cell death 1 ligand 1 (PD
      L1) axis, as well as the activity of immunogenic chemotherapies. Herein, we
      highlight some of the bacteria, such as Akkermansia muciniphila, Bacteroides
      fragilis, Bifidobacterium spp. and Faecalibacterium spp., that have been
      associated with favourable anticancer immune responses in both preclinical tumour
      models and patients with cancer. Importantly, these bacteria also seem to have a
      positive influence on general health, thus reducing the incidence of metabolic
      disorders and a wide range of chronic inflammatory pathologies. We surmise that a
      diverse and propitious microbial ecosystem favours organismal homeostasis,
      particularly at the level of the cancer-immune dialogue.

PMID- 29636540
TI  - A Study on Micropipetting Detection Technology of Automatic Enzyme Immunoassay
      Analyzer.
AB  - In order to improve the accuracy and reliability of micropipetting, a method of
      micro-pipette detection and calibration combining the dynamic pressure monitoring
      in pipetting process and quantitative identification of pipette volume in image
      processing was proposed. Firstly, the normalized pressure model for the pipetting
      process was established with the kinematic model of the pipetting operation, and
      the pressure model is corrected by the experimental method. Through the pipetting
      process pressure and pressure of the first derivative of real-time monitoring,
      the use of segmentation of the double threshold method as pipetting fault
      evaluation criteria, and the pressure sensor data are processed by Kalman
      filtering, the accuracy of fault diagnosis is improved. When there is a fault,
      the pipette tip image is collected through the camera, extract the boundary of
      the liquid region by the background contrast method, and obtain the liquid volume
      in the tip according to the geometric characteristics of the pipette tip. The
      pipette deviation feedback to the automatic pipetting module and deviation
      correction is carried out. The titration test results show that the combination
      of the segmented pipetting kinematic model of the double threshold method of
      pressure monitoring, can effectively real-time judgment and classification of the
      pipette fault. The method of closed-loop adjustment of pipetting volume can
      effectively improve the accuracy and reliability of the pipetting system.

PMID- 29636539
TI  - Dietary and Physical Activity Interventions for Colorectal Cancer Survivors: A
      Randomized Controlled Trial.
AB  - There has been evidence on the protective effects of diets high in fiber and low
      in red and processed meat (RPM), and physical activity (PA) against colorectal
      cancer (CRC) development, but that against CRC recurrence has been limited. This
      study evaluated the efficacy of a behavioral program comprising dietary and PA
      interventions in improving Chinese CRC survivors' lifestyle. A 2 * 2 factorial
      randomized controlled trial of 223 CRC patients (82 females, mean age 65),
      randomly assigned to receive dietary, PA or both interventions, or usual care for
      12 months, and assessed every 6 months for 24 months. Primary outcomes included
      two dietary and two PA targets. Secondary outcomes included changes in dietary
      consumptions and PA levels. Dietary interventions significantly increased the
      odds of achieving the targets of consuming less RPM at all time-points (OR 3.22
      4.57, all p < 0.01) and refined grain (RG) at months 6 (OR 3.13, p = 0.002) and
      24 (OR 2.19, p = 0.039), and reduced RPM (2.49-3.48 servings/week, all p < 0.01)
      and RG (0.31-0.5 servings/day, all p < 0.01) consumptions. Patients receiving PA
      interventions potentially spent more time on moderate-to-vigorous PA. This study
      demonstrated the efficacy of a behavioral program in improving dietary habits of
      Chinese CRC survivors.

PMID- 29636541
TI  - A Novel Platform for Evaluating the Environmental Impacts on Bacterial Cellulose
      Production.
AB  - Bacterial cellulose (BC) is a biocompatible material with versatile applications.
      However, its large-scale production is challenged by the limited biological
      knowledge of the bacteria. The advent of synthetic biology has lead the way to
      the development of BC producing microbes as a novel chassis. Hence, investigation
      on optimal growth conditions for BC production and understanding of the
      fundamental biological processes are imperative. In this study, we report a novel
      analytical platform that can be used for studying the biology and optimizing
      growth conditions of cellulose producing bacteria. The platform is based on
      surface growth pattern of the organism and allows us to confirm that cellulose
      fibrils produced by the bacteria play a pivotal role towards their chemotaxis.
      The platform efficiently determines the impacts of different growth conditions on
      cellulose production and is translatable to static culture conditions. The
      analytical platform provides a means for fundamental biological studies of
      bacteria chemotaxis as well as systematic approach towards rational design and
      development of scalable bioprocessing strategies for industrial production of
      bacterial cellulose.

PMID- 29636542
TI  - Understanding the drivers of MHC restriction of T cell receptors.
AB  - T cell discrimination of self and non-self is predicated on alphabeta T cell
      receptor (TCR) co-recognition of peptides presented by MHC molecules. Over the
      past 20 years, structurally focused investigations into this MHC-restricted
      response have provided profound insights into T cell function. Simultaneously,
      two models of TCR recognition have emerged, centred on whether the TCR has,
      through evolution, acquired an intrinsic germline-encoded capacity for MHC
      recognition or whether MHC reactivity is conferred by developmental selection of
      TCRs. Here, we review the structural and functional data that pertain to these
      theories of TCR recognition, which indicate that it will be necessary to
      assimilate features of both models to fully account for the molecular drivers of
      this evolutionarily ancient interaction between the TCR and MHC molecules.

PMID- 29636543
TI  - Effect of Nb concentration on the spin-orbit coupling strength in Nb-doped SrTiO3
      epitaxial thin films.
AB  - Several oxide materials have attracted much interest for the application in
      spintronic devices due to unusual properties originating from the strongly
      correlated orbital and spin degrees of freedom. One missing part in oxide
      spintronics is a good spin channel featured by strong spin-orbit coupling (SOC)
      which enables an efficient control of the electron's spin. We have systematically
      investigated the dependence of the SOC strength of Sr(Nb x Ti1-x)O3 thin films on
      Nb concentration (nNb = 2~20 at. %) as a deeper exploration of a recent finding
      of the strong SOC in a heavily Nb-doped SrTiO3 (Sr(Nb0.2Ti0.8)O3) epitaxial film.
      Apart from a finding of a proportionality of the SOC to nNb, we have observed an
      intriguing temperature dependence of the SOC strength and the anisotropic
      magnetoresistance (MR) in the intermediate nNb region. These phenomena are
      associated with the temperature dependence of Lande g-factor and the change of
      the band structure, which is consistent with the result of density functional
      theory (DFT) calculation.

PMID- 29636544
TI  - Genome-wide uniparental diploidy of all paternal chromosomes in an 11-year-old
      girl with deafness and without malignancy.
AB  - Approximately 20 cases of genome-wide uniparental disomy or diploidy (GWUPD) as
      mosaicism have previously been reported. We present the case of an 11-year-old
      deaf girl with a paternal uniparental diploidy or isodisomy with a genome-wide
      loss of heterozygosity (LOH). The patient was originally tested for non-syndromic
      deafness, and the novel variant p.V234I in the ESRRB gene was found in a
      homozygous state. Our female proband is the seventh patient diagnosed with GWUPD
      at a later age and is probably the least affected of the seven, as she has not
      yet presented any malignancy. Most, if not all, reported patients with GWUPD
      whose clinical details have been published have developed malignancy, and some of
      those patient developed malignancy several times. Therefore, our patient has a
      high risk of malignancy and is carefully monitored by a specific outpatient
      pediatric oncology program. This observation seems to be novel and unique in a
      GWUPD patient. Our study is also unique as it not only provides very detailed
      documentation of the genomic situations of various tissues but also reports
      differences in the mosaic ratios between the blood and saliva, as well as a
      normal biparental allelic situation in the skin and biliary duct. Additionally,
      we were able to demonstrate that the mosaic ratio in the blood remained stable
      even after 3 years and has not changed over a longer period.

PMID- 29636546
TI  - Redefining leukocytes in atherosclerosis.

PMID- 29636545
TI  - Osteogenesis imperfecta with ectopic mineralizations in dentin and cementum and a
      COL1A2 mutation.
AB  - We report a Thai father (patient 1) and his daughter (patient 2) affected with
      osteogenesis imperfecta type IV and dentinogenesis imperfecta. Both were
      heterozygous for the c.1451G>A (p.Gly484Glu) mutation in COL1A2. The father, a
      Thai boxer, had very mild osteogenesis imperfecta with no history of low-trauma
      bone fractures. Scanning electron micrography of the primary teeth with DI of the
      patient 2, and the primary teeth with DI of another OI patient with OI showed
      newly recognized dental manifestations of teeth with DI. Normal dentin and
      cementum might have small areas of ectopic mineralizations. Teeth affected with
      DI have well-organized ectopic mineralizations in dentin and cementum. The
      "French-fries-appearance" of the crystals at the cemento-dentinal junction and
      abnormal cementum have never been reported to be associated with dentinogenesis
      imperfecta, either isolated or osteogenesis imperfecta-associated. Our study
      shows for the first time that abnormal collagen fibers can lead to ectopic
      mineralization in dentin and cementum and abnormal cementum can be a part of
      osteogenesis imperfecta.

PMID- 29636547
TI  - BRD4 facilitates replication stress-induced DNA damage response.
AB  - Previous reports have demonstrated that select cancers depend on BRD4 to regulate
      oncogenic gene transcriptional programs. Here we describe a novel role for BRD4
      in DNA damage response (DDR). BRD4 associates with and regulates the function of
      pre-replication factor CDC6 and plays an indispensable part in DNA replication
      checkpoint signaling. Inhibition of BRD4 by JQ1 or AZD5153 resulted in a rapid,
      time-dependent reduction in CHK1 phosphorylation and aberrant DNA replication re
      initiation. Furthermore, BRD4 inhibition sensitized cancer cells to various
      replication stress-inducing agents, and synergized with ATR inhibitor AZD6738 to
      induce cell killing across a number of cancer cell lines. The synergistic
      interaction between AZD5153 and AZD6738 is translatable to in vivo ovarian cell
      line and patient-derived xenograft models. Taken together, our study uncovers a
      new biological function of BRD4 and provides mechanistic rationale for combining
      BET inhibitors with DDR-targeted agents for cancer therapy.

PMID- 29636549
TI  - Deformation behavior of dragonfly-inspired nodus structured wing in gliding
      flight through experimental visualization approach.
AB  - Dragonfly has excellent flight performance and maneuverability due to the complex
      vein structure of wing. In this research, nodus as an important structural
      element of the dragonfly wing is investigated through an experimental
      visualization approach. Three vein structures were fabricated as, open-nodus
      structure, closed-nodus structure (with a flex-limiter) and rigid wing. The
      samples were conducted in a wind tunnel with a high speed camera to visualize the
      deformation of wing structure in order to study the function of nodus structured
      wing in gliding flight. According to the experimental results, nodus has a great
      influence on the flexibility of the wing structure. Moreover, the closed-nodus
      wing (with a flex-limiter) enables the vein structure to be flexible without
      losing the strength and rigidity of the joint. These findings enhance the
      knowledge of insect-inspired nodus structured wing and facilitate the application
      of Micro Air Vehicle (MAV) in gliding flight.

PMID- 29636548
TI  - Hypoxia-induced exosomes contribute to a more aggressive and chemoresistant
      ovarian cancer phenotype: a novel mechanism linking STAT3/Rab proteins.
AB  - Hypoxia-mediated tumor progression, metastasis, and drug resistance are major
      clinical challenges in ovarian cancer. Exosomes released in the hypoxic tumor
      microenvironment may contribute to these challenges by transferring signaling
      proteins between cancer cells and normal cells. We observed that ovarian cancer
      cells exposed to hypoxia significantly increased their exosome release by
      upregulating Rab27a, downregulating Rab7, LAMP1/2, NEU-1, and also by promoting a
      more secretory lysosomal phenotype. STAT3 knockdown in ovarian cancer cells
      reduced exosome release by altering the Rab family proteins Rab7 and Rab27a under
      hypoxic conditions. We also found that exosomes from patient-derived ascites
      ovarian cancer cell lines cultured under hypoxic conditions carried more potent
      oncogenic proteins-STAT3 and FAS that are capable of significantly increasing
      cell migration/invasion and chemo-resistance in vitro and tumor
      progression/metastasis in vivo. Hypoxic ovarian cancer cells derived exosomes
      (HEx) are proficient in re-programming the immortalized fallopian tube secretory
      epithelial cells (FT) to become pro-tumorigenic in mouse fallopian tubes. In
      addition, cisplatin efflux via exosomes was significantly increased in ovarian
      cancer cells under hypoxic conditions. Co-culture of HEx with tumor cells led to
      significantly decreased dsDNA damage and increased cell survival in response to
      cisplatin treatment. Blocking exosome release by known inhibitor Amiloride or
      STAT3 inhibitor and treating with cisplatin resulted in a significant increase in
      apoptosis, decreased colony formation, and proliferation. Our results demonstrate
      that HEx are more potent in augmenting metastasis/chemotherapy resistance in
      ovarian cancer and may serve as a novel mechanism for tumor metastasis, chemo
      resistance, and a point of intervention for improving clinical outcomes.

PMID- 29636550
TI  - Distinguishing butchery cut marks from crocodile bite marks through machine
      learning methods.
AB  - All models of evolution of human behaviour depend on the correct identification
      and interpretation of bone surface modifications (BSM) on archaeofaunal
      assemblages. Crucial evolutionary features, such as the origin of stone tool use,
      meat-eating, food-sharing, cooperation and sociality can only be addressed
      through confident identification and interpretation of BSM, and more
      specifically, cut marks. Recently, it has been argued that linear marks with the
      same properties as cut marks can be created by crocodiles, thereby questioning
      whether secure cut mark identifications can be made in the Early Pleistocene
      fossil record. Powerful classification methods based on multivariate statistics
      and machine learning (ML) algorithms have previously successfully discriminated
      cut marks from most other potentially confounding BSM. However, crocodile-made
      marks were marginal to or played no role in these comparative analyses. Here, for
      the first time, we apply state-of-the-art ML methods on crocodile linear BSM and
      experimental butchery cut marks, showing that the combination of multivariate
      taphonomy and ML methods provides accurate identification of BSM, including cut
      and crocodile bite marks. This enables empirically-supported hominin behavioural
      modelling, provided that these methods are applied to fossil assemblages.

PMID- 29636551
TI  - Invasive Rosa rugosa populations outperform native populations, but some
      populations have greater invasive potential than others.
AB  - Increased performance of invasive plant species in their introduced range vs.
      their native range has been previously documented. However, performance
      differences among invasive populations have rarely been explored, despite this
      information being central to understanding the evolution of invasiveness as well
      as being a useful basis to inform management of invasive species. To examine
      variation in performance among populations of Rosa rugosa in its introduced
      range, and whether introduced populations perform better than native populations,
      we quantified growth and reproductive traits in five invasive populations in
      northwest Europe and two native and declining populations in China. Overall, we
      found that the introduced R. rugosa populations we sampled performed
      significantly better than the sampled native populations for growth and
      reproductive traits (2 to 4 fold increase). However, there was significant
      variation for most traits among the five invasive populations, demonstrating that
      some introduced populations we sampled were more successful invaders than others.
      Our findings provide a useful foundation for management of invasive R. rugosa in
      Europe, and support the recent call for more intra-species research in invasive
      species biology.

PMID- 29636553
TI  - The role of the angiotensin II type I receptor blocker telmisartan in the
      treatment of non-alcoholic fatty liver disease: a brief review.
AB  - Non-alcoholic fatty liver disease (NAFLD) is currently considered an important
      component of metabolic syndrome (MetS). The spectrum of NAFLD includes conditions
      that range from simple hepatic steatosis to non-alcoholic steatohepatitis. NAFLD
      is correlated with liver-related death and is predicted to be the most frequent
      indication for liver transplantation by 2030. Insulin resistance is directly
      correlated to the central mechanisms of hepatic steatosis in NAFLD patients,
      which is strongly correlated to the imbalance of the renin-angiotensin system,
      that is involved in lipid and glucose metabolism. Among the emerging treatment
      approaches for NAFLD is the anti-hypertensive agent telmisartan, which has
      positive effects on liver, lipid, and glucose metabolism, especially through its
      action on the renin-angiotensin system, by blocking the ACE/AngII/AT1 axis and
      increasing ACE2/Ang(1-7)/Mas axis activation. However, treatment with this drug
      is only recommended for patients with an established indication for anti
      hypertensive therapy. Thus, there is an increased need for large randomized
      controlled trials with the aim of elucidating the effects of telmisartan on liver
      disease, especially NAFLD. From this perspective, the present review aims to
      provide a brief examination of the pathogenesis of NAFLD/NASH and the role of
      telmisartan on preventing liver disorders and thus to improve the discussion on
      potential therapies.

PMID- 29636552
TI  - Calorie restriction is the most reasonable anti-ageing intervention: a meta
      analysis of survival curves.
AB  - Despite technological advances, the survival records from longevity experiments
      remain the most indispensable tool in ageing-related research. A variety of
      interventions, including medications, genetic manipulations and calorie
      restriction (CR), have been demonstrated to extend the lifespan of several
      species. Surprisingly, few systematic studies have investigated the differences
      among these anti-ageing strategies using survival data. Here, we conduct a
      comprehensive and comparative meta-analysis of numerous published studies on
      Caenorhabditis elegans and Drosophila. We found that CR and genetic manipulations
      are generally more effective than medications at extending the total lifespan in
      both models, and CR can improve the ageing pattern of C. elegans. We further
      analysed the survival variation for different anti-ageing medications and
      determined that hypoglycaemic agents and antioxidants are advantageous despite
      only moderately increasing the overall lifespan; therefore, these two types of
      medications are promising CR mimetics. Analysis of genetic manipulations also
      indicated that the genes or pathways that extend lifespan in a healthier pattern
      are associated with CR. These results suggest that CR or CR mimetics may be the
      most reasonable and potentially beneficial anti-ageing strategy.

PMID- 29636554
TI  - An investigation of the mechanical and microstructural evolution of a TiNbZr
      alloy with varied ageing time.
AB  - Alloys comprised of the highly biocompatible elements titanium, niobium and
      zirconium have been a major focus in recent years in the field of metallic
      biomaterials. To contribute to the corpus of data in this field, the current
      paper presents results from a thorough microstructural and mechanical
      investigation of Ti-32Nb-6Zr subjected to a variety of ageing treatments. The
      presented alloy was stabilized to the higher temperature, body-centred cubic
      phase, showing only minimal precipitation on prolonged ageing, despite the
      presence of nanoscaled spinodal segregation arising from the Nb-Zr interaction.
      It further showed excellent mechanical properties, with tensile yield stresses as
      high as 820 MPa and Young's moduli as low as 53 GPa. This leads to the ratio of
      strength to modulus, also known as the admissible strain, reaching a maximum of
      1.3% after 6 hours ageing. These results are further supported by similar
      measurements from nanoindentation analysis.

PMID- 29636556
TI  - North Atlantic circulation slows down.

PMID- 29636557
TI  - The certainty of randomness.

PMID- 29636559
TI  - A molecule that manufactures asymmetry.

PMID- 29636558
TI  - Convert your weaknesses into assets.

PMID- 29636561
TI  - Cancer research with a human touch.

PMID- 29636555
TI  - Expert consensus document: Advances in the evaluation of anorectal function.
AB  - Faecal incontinence and evacuation disorders are common, impair quality of life
      and incur substantial economic costs worldwide. As symptoms alone are poor
      predictors of underlying pathophysiology and aetiology, diagnostic tests of
      anorectal function could facilitate patient management in those cases that are
      refractory to conservative therapies. In the past decade, several major
      technological advances have improved our understanding of anorectal structure,
      coordination and sensorimotor function. This Consensus Statement provides the
      reader with an appraisal of the current indications, study performance
      characteristics, clinical utility, strengths and limitations of the most widely
      available tests of anorectal structure (ultrasonography and MRI) and function
      (anorectal manometry, neurophysiological investigations, rectal distension
      techniques and tests of evacuation, including defecography). Additionally, this
      article provides our consensus on the clinical relevance of these tests.

PMID- 29636563
TI  - Mice show motherly habits when a brain circuit fires.

PMID- 29636564
TI  - Why fat piles on when the body's daily cycles are in disarray.

PMID- 29636562
TI  - Collaboration is the key to cancer research.

PMID- 29636565
TI  - A chance to save Arctic sea ice.

PMID- 29636566
TI  - Jekyll and Hyde, a story of two galaxies.

PMID- 29636567
TI  - An absorbing study on the maths of sponges.

PMID- 29636568
TI  - Dexterous sea turtles use flippers as grippers.

PMID- 29636569
TI  - A squid-skin-inspired invisibility cloak.

PMID- 29636570
TI  - Beijing launches pioneering brain-science centre.

PMID- 29636572
TI  - NASA's next exoplanet hunter will seek worlds close to home.

PMID- 29636571
TI  - Plan to dismantle Puerto Rico's statistics agency gets green light.

PMID- 29636573
TI  - How a chicken makes a good egg.

PMID- 29636574
TI  - Cutting-edge cancer drug hobbled by diagnostic test confusion.

PMID- 29636575
TI  - The telomerase enzyme and liver renewal.

PMID- 29636576
TI  - Science's vast gender pay gap revealed in UK wage data.

PMID- 29636577
TI  - Demand cancer drugs that truly help patients.

PMID- 29636579
TI  - Planet of the microorganisms.

PMID- 29636578
TI  - Mirrors made of a single atomic layer.

PMID- 29636580
TI  - A new metallene arrival.

PMID- 29636581
TI  - Sensing hot electrons.

PMID- 29636582
TI  - A tailored snip.

PMID- 29636583
TI  - Scalable thermal insulator.

PMID- 29636584
TI  - Science and style.

PMID- 29636585
TI  - Denominational interpretations of nanotech.

PMID- 29636586
TI  - Quantum dots on your mind.

PMID- 29636587
TI  - 2D magnetism gets hot.

PMID- 29636588
TI  - Low-energy desalination.

PMID- 29636589
TI  - Evaluating the potential of using quantum dots for monitoring electrical signals
      in neurons.
AB  - Success in the projects aimed at providing an advanced understanding of the brain
      is directly predicated on making critical advances in nanotechnology. This
      Perspective addresses the unique interface of neuroscience and nanomaterials by
      considering the foundational problem of sensing neuron membrane voltage and
      offers a potential solution that may be facilitated by a prototypical
      nanomaterial. Despite substantial improvements, the visualization of
      instantaneous voltage changes within individual neurons, whether in cell culture
      or in vivo, at both the single-cell and network level at high speed remains
      complex and problematic. The unique properties of semiconductor quantum dots
      (QDs) have made them powerful fluorophores for bioimaging. What is not widely
      appreciated, however, is that QD photoluminescence is exquisitely sensitive to
      proximal electric fields. This property should be suitable for sensing voltage
      changes that occur in the active neuronal membrane. Here, we examine the
      potential role of QDs in addressing the important challenge of real-time optical
      voltage imaging.

PMID- 29636591
TI  - Snow Grain Size Retrieval over the Polar Ice Sheets with the Ice, Cloud, and land
      Elevation Satellite (ICESat) Observations.
AB  - Snow grain size is an important parameter for cryosphere studies. As a proof of
      concept, this paper presents an approach to retrieve this parameter over
      Greenland, East and West Antarctica ice sheets from surface reflectances observed
      with the Geoscience Laser Altimeter System (GLAS) onboard the Ice, Cloud, and
      land Elevation Satellite (ICESat) at 1064 nm. Spaceborne lidar observations
      overcome many of the disadvantages in passive remote sensing, including
      difficulties in cloud screening and low sun angle limitations; hence tend to
      provide more accurate and stable retrievals. Results from the GLAS L2A campaign,
      which began on 25 September and lasted until 19 November, 2003, show that the
      mode of the grain size distribution over Greenland is the largest (~300 MUm)
      among the three, West Antarctica is the second (~220 MUm) and East Antarctica is
      the smallest (~190 MUm). Snow grain sizes are larger over the coastal regions
      compared to inland the ice sheets. These results are consistent with previous
      studies. Applying the broadband snow surface albedo parameterization scheme
      developed by Garder and Sharp (2010) to the retrieved snow grain size, ice sheet
      surface albedo is also derived. In the future, more accurate retrievals can be
      achieved with multiple wavelengths lidar observations.

PMID- 29636590
TI  - The Convective Transport of Active Species in the Tropics (CONTRAST) Experiment.
AB  - The Convective Transport of Active Species in the Tropics (CONTRAST) experiment
      was conducted from Guam (13.5 degrees  N, 144.8 degrees  E) during January
      February 2014. Using the NSF/NCAR Gulfstream V research aircraft, the experiment
      investigated the photochemical environment over the tropical western Pacific
      (TWP) warm pool, a region of massive deep convection and the major pathway for
      air to enter the stratosphere during Northern Hemisphere (NH) winter. The new
      observations provide a wealth of information for quantifying the influence of
      convection on the vertical distributions of active species. The airborne in situ
      measurements up to 15 km altitude fill a significant gap by characterizing the
      abundance and altitude variation of a wide suite of trace gases. These
      measurements, together with observations of dynamical and microphysical
      parameters, provide significant new data for constraining and evaluating global
      chemistry climate models. Measurements include precursor and product gas species
      of reactive halogen compounds that impact ozone in the upper troposphere/lower
      stratosphere. High accuracy, in-situ measurements of ozone obtained during
      CONTRAST quantify ozone concentration profiles in the UT, where previous
      observations from balloon-borne ozonesondes were often near or below the limit of
      detection. CONTRAST was one of the three coordinated experiments to observe the
      TWP during January-February 2014. Together, CONTRAST, ATTREX and CAST, using
      complementary capabilities of the three aircraft platforms as well as ground
      based instrumentation, provide a comprehensive quantification of the regional
      distribution and vertical structure of natural and pollutant trace gases in the
      TWP during NH winter, from the oceanic boundary to the lower stratosphere.

PMID- 29636592
TI  - An Idealised Test Case For Assessing The Linearization of Tracer Transport
      Schemes in NWP Models.
AB  - The linearized version of a Numerical Weather Prediction (NWP) model, which
      consists of its tangent linear model (TLM) and adjoint, has a number of important
      applications in atmospheric modelling. As such it is important that the
      linearized version of the NWP model can provide an accurate representation of the
      perturbation growth that occurs in the nonlinear model and does not introduce
      spurious instability. A suite of test cases, built upon existing frameworks, are
      developed to assess the accuracy of the linearization of the tracer transport
      component of the NWP model. Deformation velocities are prescribed that return the
      tracer back to the initial conditions, thus providing an analytical solution. A
      selection of smooth and discontinuous tracers and tracer perturbations are used.
      Example results are shown using second-order and third-order tracer transport
      schemes, both with and without nonlinear flux limiters. Metrics are offered for
      assessing the skill of the linearization and predicting when problems will occur.
      For the example schemes used the results show that linearizations of the
      nonlinear flux-limited transport schemes behave poorly due to the presence of
      unstable modes. Some linearized model implementation strategies are offered for
      situations where the nonlinear scheme should not be linearized.

PMID- 29636593
TI  - The MAPK-Signaling Pathway in Colorectal Cancer: Dysregulated Genes and Their
      Association With MicroRNAs.
AB  - Mitogen-activated protein kinase (MAPK) pathways regulate many cellular functions
      including cell proliferation and apoptosis. We examined associations of
      differential gene and microRNA (miRNA) expression between carcinoma and paired
      normal mucosa for 241 genes in the KEGG-identified MAPK-signaling pathway among
      217 colorectal cancer (CRC) cases. Gene expression data (RNA-Seq) and miRNA
      expression data (Agilent Human miRNA Microarray V19.0; Agilent Technologies Inc.,
      Santa Clara, CA, USA) were analyzed. We first identified genes most strongly
      associated with CRC using a fold change (FC) of >1.50 or <0.67) that were
      statistically significant after adjustment for multiple comparisons. We then
      determined miRNAs associated with dysregulated genes and through miRNA:mRNA
      (messenger RNA) seed region matches discerned genes with a greater likelihood of
      having a direct biological association. Ninety-nine genes had a meaningful FC for
      all CRC, microsatellite unstable-specific tumors, or microsatellite stable
      specific tumors. Thirteen dysregulated genes were associated with miRNAs,
      totaling 68 miRNA:mRNA associations. Thirteen of the miRNA:mRNA associations had
      seed region matches where the differential expression between the miRNA and mRNA
      was inversely related suggesting a direct association as a result of their
      binding. Several direct associations, upstream of ERK1/ERK2, JNK, and p38, were
      found for PDGFRA with 7 miRNAs; RASGRP3 and PRKCB with miR-203a; and TGFBR1 with
      miR-6071 and miR-2117. Other associations between miRNAs and mRNAs are most
      likely indirect, resulting from feedback and feed forward loops. Our results
      suggest that miRNAs may alter MAPK signaling through direct binding with key
      genes in this pathway. We encourage others to validate results in targeted CRC
      experiments that can help solidify important therapeutic targets.

PMID- 29636594
TI  - Ranibizumab treatment history as predictor of the switch-response to aflibercept:
      evidence for drug tolerance.
AB  - Purpose: To investigate whether tolerance to the anti-VEGF drug, ranibizumab,
      develops after drug exposure and to determine whether the history of treatment
      with ranibizumab prior to refractoriness can predict the post-switching responses
      to aflibercept. Methods: We retrospectively investigated neovascular age-related
      macular degeneration patients refractory to ranibizumab (intra- or subretinal
      fluid despite monthly injections for >=6 months) who were switched to aflibercept
      and were followed up for at least 12 months on each of ranibizumab and
      aflibercept. Baseline characteristics and ranibizumab and aflibercept treatment
      history (number of injections during the first year and central retinal thickness
      [CRT]) were analyzed by univariate and multivariate correlation analyses.
      Results: Ninety-eight eyes (88 patients, 70% females, mean age 77.5 years),
      including a high proportion of eyes with pigment epithelium detachment (63%),
      were treated with a mean of 26.2 injections during 36.8 months before switching
      to aflibercept. The number of ranibizumab injections required in the first year
      (p=0.0002) and the presence of pigment epithelium detachment (p=0.025) predicted
      the number of post-switching aflibercept injections required. The post-switching
      CRT change was predicted by the CRT increase from Month 3 to the switch time
      point (p<0.0001). Moreover, the CRT change correlated with the visual acuity
      benefit post-switching (p=0.038 and p=0.004, at 3 and 12 months post-switching,
      respectively). Conclusion: Ranibizumab treatment history before switching to
      aflibercept correlates with the post-switching response in terms of the number of
      drug injections needed and CRT. Thus, drug tolerance does indeed exist and this
      might help to identify switching candidates.

PMID- 29636595
TI  - Visual acuity, endothelial cell density and polymegathism after iris-fixated lens
      implantation.
AB  - Purpose: The purpose of this study was to evaluate the visual acuity as well as
      endothelial cell density (ECD) and polymegathism after iris-fixated lens
      (Artiflex(r) AC 401) implantation for correction of moderate to high myopia.
      Patients and methods: In this retrospective cross-sectional study, 55 eyes from
      29 patients undergoing iris-fixated lens implantation for correction of myopia (
      5.00 to -15.00 D) from 2007 to 2014 were evaluated. Uncorrected visual acuity,
      best spectacle-corrected visual acuity, refraction, ECD and polymegathism
      (coefficient of variation [CV] in the sizes of endothelial cells) were measured
      preoperatively and 6 months postoperatively. Results: In the sixth month of
      follow-up, the uncorrected vision acuity was 20/25 or better in 81.5% of the
      eyes. The best-corrected visual acuity was 20/30 or better in 96.3% of the eyes,
      and more than 92% of the eyes had a refraction score of +/-1 D from the target
      refraction. The mean corneal ECD of patients before surgery was 2,803+/-339
      cells/mm2, which changed to 2,744+/-369 cells/mm2 six months after surgery
      (p=0.142). CV in the sizes of endothelial cells before the surgery was 25.7%+/
      7.1% and six months after surgery it was 25.9%+/-5.4% (p=0.857). Conclusion:
      Artiflex iris-fixated lens implantation is a suitable and predictable method for
      correction of moderate to high myopia. There was no statistically significant
      change in ECD and polymegathism (CV in the sizes of endothelial cells) after 6
      months of follow-up.

PMID- 29636596
TI  - Comparison of macular thickness by optical coherence tomography measurements
      after uneventful phacoemulsification using ketorolac tromethamine, nepafenac, vs
      a control group, preoperatively and postoperatively.
AB  - Purpose: To analyze, using optical coherence tomography, the macular thickness
      values of patient groups using nonsteroidal anti-inflammatory drug (NSAID) eye
      drops or artificial tears during uncomplicated cataract surgery. Methods: A total
      of 77 eyes from 42 patients were analyzed. The patients were divided into three
      groups, each using one of the following ophthalmic sterile suspensions: nepafenac
      (21 eyes), propylene glycol (24 eyes), or ketorolac tromethamine (32 eyes).
      Results: The mean macular thicknesses of the nepafenac group, preoperatively as
      well as at 1, 7, and 45 days postoperatively, were 216.42, 216.61, 222.47, and
      218.28, respectively; those of the propylene glycol control group were 218.29,
      214.50, 219.37, and 228.45, respectively; and those of the ketorolac tromethamine
      group were 217.46, 220.71, 225.25, and 228.46, respectively. There were no
      significant differences between groups at any time, with p-values of 0.971,
      0.6742, 0.6711, and 0.327, respectively. Conclusion: During the study period, no
      significant differences in macular thickness were observed between the patient
      groups using two types of NSAIDs or between those groups and the control group
      that used propylene glycol, indicating that neither drug was superior to the
      other or the placebo. However, a slight macular thickening, without reduction of
      visual acuity, was observed in all groups.

PMID- 29636597
TI  - Comparison of simulated keratometric changes following wavefront-guided and
      wavefront-optimized myopic laser-assisted in situ keratomileusis.
AB  - Purpose: The aim of the study was to determine and compare the relationship
      between change in simulated keratometry (K) and degree of refractive correction
      in wavefront-guided (WFG) and wavefront-optimized (WFO) myopic laser-assisted in
      situ keratomileusis (LASIK). Methods: A total of 51 patients were prospectively
      randomized to WFG LASIK in one eye and WFO LASIK in the contralateral eye at the
      Byers Eye Institute, Stanford University. Changes in simulated K and refractive
      error were determined at 1 year post-operatively. Linear regression was employed
      to calculate the slope of change in simulated K (DeltaK) for change in refractive
      error (DeltaSE). The mean ratio (DeltaK/DeltaSE) was also calculated. Results:
      The ratio of DeltaK to DeltaSE was larger for WFG LASIK compared to WFO LASIK
      when comparing the slope (DeltaK/DeltaSE) as determined by linear regression
      (0.85 vs 0.83, p = 0.04). Upon comparing the mean ratio (DeltaK/DeltaSE),
      subgroup analysis revealed that DeltaK/DeltaSE was larger for WFG LASIK for
      refractive corrections of >3.00 D and >4.00 D (0.89 vs 0.83; p = 0.0323 and 0.88
      vs 0.83; p = 0.0466, respectively). Both linear regression and direct comparison
      of the mean ratio (DeltaK/DeltaSE) for refractive corrections <4.00 D and >4.00 D
      revealed no difference in DeltaK/DeltaSE between smaller and larger refractive
      corrections. Conclusion: WFO LASIK requires a smaller amount of corneal
      flattening compared to WFG LASIK for a given degree of refractive correction. For
      both, there was no significant difference in change in corneal curvature for a
      given degree of refractive error between smaller and larger corrections.

PMID- 29636598
TI  - The role of propranolol as a radiosensitizer in gastric cancer treatment.
AB  - Purpose: The National Comprehensive Cancer Network guidelines indicate that
      radiotherapy in gastric cancer shows limited effectiveness at reducing the growth
      of gastric cancer. Therefore, enhancing the sensitivity and effect of
      radiotherapy with propranolol, a beta-adrenoceptor antagonist, could reduce tumor
      growth. The role of propranolol as a radiosensitizer has not been adequately
      studied; therefore, the purpose of the present study is to evaluate the effect of
      propranolol as a radiosensitizer against gastric cancer in vivo. Methods: Sixty
      four male nude mice bearing tumor xenografts were randomly divided into four
      groups. Cell culture was performed using the human gastric adenocarcinoma cell
      line SGC-7901. Mice with tumor xenografts were treated with propranolol,
      isoproterenol, and radiation. The data for tumor weight and volume were obtained
      for statistical analyses. Furthermore, the expression levels of COX-2, NF-kappaB,
      VEGF, and EGFR were examined using immunohistochemical techniques and Western
      blotting. Results: The growth in the volume and weight of the tumor was lower in
      mouse models treated with propranolol and radiation therapy compared to the other
      groups. Decreased expression of NF-kappaB was also observed in treatment groups
      where both propranolol and radiation were used, leading to the reduction of COX
      2, EGFR, and VEGF expression compared to that in the other groups. Conclusion:
      The present study indicated that propranolol potentiates the antitumor effects of
      radiotherapy in gastric cancer by inhibiting NF-kappaB expression and its
      downstream genes: VEGF, EGFR, and COX-2.

PMID- 29636599
TI  - Comparison of oral dexmedetomidine and midazolam for premedication and emergence
      delirium in children after dental procedures under general anesthesia: a
      retrospective study.
AB  - Background: Premedication is the most common way to minimize distress in children
      entering the operating room and to facilitate the smooth induction of anesthesia
      and is accomplished using various sedative drugs before the children are being
      transferred to the operating room. The aim of this study was to compare the
      effect of oral dexmedetomidine (DEX) and oral midazolam (MID) on preoperative
      cooperation and emergence delirium (ED) among children who underwent dental
      procedures at our hospital between 2016 and 2017. Patients and methods: The
      medical records of 52 children, who were American Society of Anesthesiologists I,
      aged between 3 and 7 years, and who underwent full-mouth dental rehabilitation
      under general anesthesia (GA), were evaluated. Twenty-six patients were given 2
      ug/kg of DEX, while another 26 patients were given 0.5 mg/kg of MID in apple
      juice as premedication agents. The patients' scores on the Ramsay Sedation Scale
      (RSS), Parental Separation Anxiety Scale (PSAS), Mask Acceptance Scale, Pediatric
      Anesthesia Emergence Delirium Scale (PAEDS), and hemodynamic parameters were
      recorded from patients' files. The level of sedation of children had been
      observed just before premedication and at 15, 30, and 45 min after premedication.
      The data were analyzed using a chi-square test, Fisher's exact test, Student's t
      test, and analysis of variance in SPSS. Results: The Mask Acceptance Scale and
      PSAS scores and RSS scores at 15, 30, and 45 min after premedication were not
      statistically different (p>0.05) in both groups, whereas the PAEDS scores were
      significantly lower in the DEX group (p<0.05). Conclusion: Oral DEX provided
      satisfactory sedation levels, ease of parental separation, and mask acceptance in
      children in a manner similar to MID. Moreover, children premedicated with DEX
      experienced lesser ED than those premedicated with MID.

PMID- 29636600
TI  - The apoptotic effects of Brucea javanica fruit extract against HT29 cells
      associated with p53 upregulation and inhibition of NF-kappaB translocation.
AB  - Background: Brucea javanica (L.) Merr. is a plant from the genus Brucea, which is
      used in local traditional medicine to treat various diseases. Recent studies
      revealed an impressive anticancer efficiency of B. javanica extract in different
      types of cancer cells. Purpose: In this study, we have investigated the cytotoxic
      effects of the B. javanica hexane, ethanolic extracts against colon cancer cells.
      HT29 colon cells were selected as an in vitro cancer model to evaluate the
      anticancer activity of B. javanica ethanolic extract (BJEE) and the possible
      mechanisms of action that induced apoptosis. Methods: 3-(4,5-dimethylthiazol-2
      yl)-2, 5,-diphenyltetrazolium bromide (MTT), lactate dehydrogenase, acridine
      orange/propidium iodide, and annexin-V-fluorescein isothiocyanate assays were
      performed to determine the antiproliferative and apoptosis validation of BJEE on
      cancer cells. Measurement of reactive oxygen species (ROS) production, caspase
      activities, nucleus factor-kappaB activity, and gene expression experiments was
      done to investigate the potential mechanisms of action in the apoptotic process.
      Results: The results obtained from this study illustrated the significant
      antiproliferative effect of BJEE on colorectal cancer cells, with a concentration
      value that inhibits 50% of the cell growth of 25+/-3.1 ug/mL after 72 h of
      treatment. MTT assay demonstrated that the BJEE is selectively toxic to cancer
      cells, and BJEE induced cell apoptosis via activation of caspase-8 along with
      modulation of apoptosis-related proteins such as Fas, CD40, tumor necrosis factor
      related apoptosis-inducing ligands, and tumor necrosis factor receptors, which
      confirmed the contribution of extrinsic pathway. Meanwhile, increased ROS
      production in treated cells subsequently activated caspase-9 production, which
      triggered the intrinsic pathways. In addition, overexpression of cytochrome-c,
      Bax, and Bad proteins along with suppression of Bcl-2 illustrated that
      mitochondrial-dependent pathway also contributed to BJEE-induced cell death.
      Consistent with the findings from this study, BJEE-induced cancer cell death
      proceeds via extrinsic and intrinsic mitochondrial-dependent and -independent
      events. Conclusion: From the evidence obtained from this study, it is concluded
      that the BJEE is a promising natural extract to combat colorectal cancer cells
      (HT29 cells) via induction of apoptosis through activation of extrinsic and
      intrinsic pathways.

PMID- 29636601
TI  - Anticancer activity of the intraperitoneal-delivered DFP-10825, the cationic
      liposome-conjugated RNAi molecule targeting thymidylate synthase, on peritoneal
      disseminated ovarian cancer xenograft model.
AB  - Introduction: Peritoneal disseminated ovarian cancer is one of the most difficult
      cancers to treat with conventional anti-cancer drugs and the treatment options
      are very limited, although an intraperitoneal (ip) paclitaxel has shown some
      clinical benefit. Therefore, treatment of peritoneal disseminated ovarian cancer
      is a highly unmet medical need and it is urgent to develop a new ip delivered
      drug regulating the fast DNA synthesis. Methods: We developed a unique RNAi
      molecule consisting of shRNA against the thymidylate synthase (TS) and a cationic
      liposome (DFP-10825) and tested its antitumor activity and PK profile in
      peritoneally disseminated human ovarian cancer ascites models by the luciferase
      gene-transfected SCID mice. DFP-10825 alone, paclitaxel alone or combination with
      DFP-10825 and paclitaxel were administered in an ip route to the tumor-bearing
      mice. The TS expression level was measured by conventional RT-PCR. The anti-tumor
      activity and host survival benefit by DFP-10825 treatment on tumor-bearing mice
      were observed as resulting from the specific TS mRNA knock-down in tumors.
      Results: DFP-10825 alone significantly suppressed the growth of SKOV3-luc tumore
      ascites cells and further extended the survival time of these tumor-bearing mice.
      Combination with the ip paclitaxel augmented the antitumor efficacy of DFP-10825
      and significantly prolonged the survival time in the tumor-bearing mice. Short
      hairpin RNA for TS (TS shRNA) levels derived from DFP-10825 in the ascetic fluid
      were maintained at a nM range across 24 hours but not detected in the plasma,
      suggesting that TS shRNA is relatively stable in the peritoneal cavity, to be
      able to exert its anti-tumor activity, but not in blood stream, indicating little
      or no systemic effect. Conclusion: Collectively, the ip delivery of DFP-10825, TS
      shRNA conjugated with cationic liposome, shows a favorable antitumor activity
      without systemic adverse events via the stable localization of TS shRNA for a
      sufficient time and concentration in the peritoneal cavity of the peritoneally
      disseminated human ovarian cancer-bearing mice.

PMID- 29636603
TI  - Total knee arthroplasty status and patient-reported, knee-related quality of life
      over a 4-year follow-up period: data from the osteoarthritis initiative.
AB  - Purpose: To examine the relationship between baseline total knee arthroplasty
      (TKA) status and patient-reported, knee-related quality of life (QoL) over a 4
      year follow-up relative to no knee osteoarthritis (OA). Patients and methods:
      Data from the Osteoarthritis Initiative were included, comprising 4,674 adults
      aged 45-79 years at baseline. Patients were categorized into four groups: no knee
      OA (n=3,711), non-TKA (n=902), pre-TKA (n=36), and post-TKA (n=25). QoL was
      measured using the Knee Injury Osteoarthritis Outcome Score-QoL subscale. General
      linear mixed models were used for the relationship between TKA and QoL. Results:
      After adjusting for covariates, a reduced QoL was noted for patients in the non
      TKA (mean [standard error], -13.97 [0.73]; P<0.0001), pre-TKA (-21.34 [3.57];
      P<0.0001), and post-TKA (-9.68 [3.94]; P=0.0143) groups compared with the no knee
      OA group. QoL in the non-TKA group also decreased over time (-0.16 [0.07];
      P=0.226). Conclusion: Non-, pre-, and post-TKA status is associated with a lower
      QoL.

PMID- 29636602
TI  - Organic mononitrites of 1,2-propanediol act as an effective NO-releasing
      vasodilator in pulmonary hypertension and exhibit no cross-tolerance with
      nitroglycerin in anesthetized pigs.
AB  - Purpose: Clinically available intravenous (IV) nitric oxide (NO) donor drugs such
      as nitroglycerin (GTN) cause systemic hypotension and/or tolerance development.
      In a porcine model, novel NO donor compounds - the organic mononitrites of 1,2
      propanediol (PDNO) - were compared to GTN with regard to pulmonary selectivity
      and tolerance development. The vasodilatory effects of inorganic nitrite were
      investigated. Materials and methods: In anesthetized piglets, central
      hemodynamics were monitored. At normal pulmonary vascular resistance (PVR), IV
      infusions of PDNO (15-60 nmol kg-1 min-1), GTN (13-132 nmol kg-1 min-1), and
      inorganic nitrite (dosed as PDNO) were administered. At increased PVR (by U46619
      IV), IV infusions of PDNO (60-240 nmol kg-1 min-1) and GTN (75-300 nmol kg-1 min
      1) before and after a 5 h infusion of GTN (45 nmol kg-1 min-1) were given.
      Results: At normal PVR, PDNO (n=12) and GTN (n=7) caused significant dose
      dependent decreases in mean systemic and pulmonary arterial pressures, whereas
      inorganic nitrite (n=13) had no significant effect. At increased PVR, PDNO (n=6)
      and GTN (n=6) significantly decreased mean systemic and pulmonary pressures and
      resistances, but only PDNO reduced the ratio between pulmonary and systemic
      vascular resistances significantly. After the 5 h GTN infusion, the hemodynamic
      response to GTN infusions (n=6) was significantly suppressed, whereas PDNO (n=6)
      produced similar hemodynamic effects to those observed before the GTN infusion.
      Conclusion: PDNO is a vasodilator with selectivity for pulmonary circulation
      exhibiting no cross-tolerance to GTN, but GTN causes non selective vasodilatation
      with substantial tolerance development in the pulmonary and systemic
      circulations. Inorganic nitrite has no vasodilatory properties at relevant doses.

PMID- 29636604
TI  - CHA2DS2-VASc score as a predictor of long-term cardiac outcomes in elderly
      patients with or without atrial fibrillation.
AB  - Background: The CHA2DS2-VASc score is often used for stroke risk stratification
      in atrial fibrillation (AF) patients. However, its usefulness in patients >=75
      years of age with or without AF is unclear. Objective: We aimed to investigate
      whether the CHA2DS2-VASc score can predict ischemic stroke (IS), transient
      ischemic attack, thromboembolism (TE), and mortality in elderly patients with and
      without AF. Materials and methods: During 2013-2014, 1,071 patients (36.3% with
      concomitant AF) at least 75 years old were enrolled, and the follow-up ended on
      July 15, 2017. Variables included sociodemographic characteristics,
      complications, drugs taken, laboratory results, and echocardiographic parameters.
      The primary end points were IS, transient ischemic attack, and TE, expressed as
      IS/TE. All-cause mortality was a secondary end point. Survival curves and
      mortality risks were assessed via Kaplan-Meier survival analysis and compared by
      log-rank tests. Results: The average follow-up duration was 2.57+/-1.37 years.
      Overall, 167 patients (5.6%) died and 77 (7.2%) developed IS/TE. The CHA2DS2-VASc
      score was associated with IS/TE in patients 75 years or older with and without
      AF, and patients with a CHA2DS2-VASc score >=5 had a higher risk of stroke.
      However, the CHA2DS2-VASc score was not related to all-cause mortality.
      Conclusion: The CHA2DS2-VASc score can predict IS/TE, but not mortality, in
      elderly patients (>=75 years) with or without AF.

PMID- 29636605
TI  - Is grand multiparity a risk factor for the development of postmenopausal
      osteoporosis?
AB  - Objective: In this study, we investigated the relationship between the
      development of postmenopausal osteoporosis and parity. Materials and methods: The
      retrospective study included 129 postmenopausal women who were divided into three
      groups depending on the number of parity: Group I, <5; Group II, 5-9; and Group
      III, >=10. The mean age of the subjects was 57.71+/-5.02 years. Results: No
      significant difference was found among the three groups regarding body mass index
      values, duration of menopause, mean thyroid stimulating hormone values and
      frequency of diabetes. Among the three groups, no significant difference was
      found in terms of the frequency of lumbar osteoporosis (p>0.05), whereas a
      significant difference was found regarding the frequency of femoral osteoporosis
      (p=0.012; p<0.05). Conclusion: It was revealed that femoral bone mineral density
      significantly decreased as the number of parity increased.

PMID- 29636606
TI  - Enhanced permeability of blood-brain barrier and targeting function of brain via
      borneol-modified chemically solid lipid nanoparticle.
AB  - Introduction: The incidence of central nervous system disease has increased in
      recent years. However, the transportation of drug is restricted by the blood
      brain barrier, contributing to the poor therapeutic effect in the brain.
      Therefore, the development of a new brain-targeting drug delivery system has
      become the hotspot of pharmacy. Materials and methods: Borneol, a simple bicyclic
      monoterpene extracted from Dryobalanops aromatica, can direct drugs to the upper
      body parts according to the theory of traditional Chinese medicine. Dioleoyl
      phosphoethanolamine (DOPE) was chemically modified by borneol as one of the lipid
      materials of solid lipid nanoparticle (SLN) in the present study. Results: The
      borneol-modified chemically solid lipid nanoparticle (BO-SLN/CM), borneol
      modified physically solid lipid nanoparticle (BO-SLN/PM), and SLN have similar
      diameter (of about 87 nm) and morphological characteristics. However, BO-SLN/CM
      has a lower cytotoxicity, higher cell uptake, and better blood-brain barrier
      permeability compared with BO-SLN/PM and SLN. BO-SLN/CM has a remarkable
      targeting function to the brain, while BO-SLN/ PM and SLNs are concentrated at
      the lung. Conclusion: The present study provides an excellent drug delivery
      carrier, BO-SLN/CM, having the application potential of targeting to the brain
      and permeating to the blood-brain barrier.

PMID- 29636607
TI  - Microstructures, mechanical, and biological properties of a novel Ti-6V-4V/zinc
      surface nanocomposite prepared by friction stir processing.
AB  - Background: The interaction between the material and the organism affects the
      survival rate of the orthopedic or dental implant in vivo. Friction stir
      processing (FSP) is considered a new solid-state processing technology for
      surface modification. Purpose: This study aims to strengthen the surface
      mechanical properties and promote the osteogenic capacity of the biomaterial by
      constructing a Ti-6Al-4V (TC4)/zinc (Zn) surface nanocomposites through FSP.
      Methods: FSP was used to modify the surface of TC4. The microstructures and
      mechanical properties were analyzed by scanning electron microscopy, transmission
      electron microscopy, nanoindentation and Vickers hardness. The biological
      properties of the modified surface were evaluated by the in vitro and in vivo
      study. Results: The results showed that nanocrystalline and numerous beta
      regions, grain boundary alpha phase, coarser acicular alpha phase and finer
      acicular martensite alpha' appeared because of the severe plastic deformation
      caused by FSP, resulting in a decreased elastic modulus and an increased surface
      hardness. With the addition of Zn particles and the enhancement of
      hydrophilicity, the biocompatibility was greatly improved in terms of cell
      adhesion and proliferation. The in vitro osteogenic differentiation of rat bone
      marrow stromal cells and rapid in vivo osseointegration were enhanced on the
      novel TC4/Zn metal matrix nanocomposite surface. Conclusion: These findings
      suggest that this novel TC4/Zn surface nanocomposite achieved by FSP has
      significantly improved mechanical properties and biocompatibility, in addition to
      promoting osseointegration and thus has potential for dental and orthopedic
      applications.

PMID- 29636608
TI  - Dextran-coated superparamagnetic iron oxide nanoparticles for magnetic resonance
      imaging: evaluation of size-dependent imaging properties, storage stability and
      safety.
AB  - Background: Rising criticism of currently available contrast agents for magnetic
      resonance imaging, either due to their side effects or limited possibilities in
      terms of functional imaging, evoked the need for safer and more versatile agents.
      We previously demonstrated the suitability of novel dextran-coated
      superparamagnetic iron oxide nanoparticles (SPIONDex) for biomedical applications
      in terms of safety and biocompatibility. Methods: In the present study, we
      investigated the size-dependent cross-linking process of these particles as well
      as the size dependency of their imaging properties. For the latter purpose, we
      adopted a simple and easy-to-perform experiment to estimate the relaxivity of the
      particles. Furthermore, we performed an extensive analysis of the particles'
      storage stability under different temperature conditions, showing their superb
      stability and the lack of any signs of agglomeration or sedimentation during a 12
      week period. Results: Independent of their size, SPIONDex displayed no irritation
      potential in a chick chorioallantoic membrane assay. Cell uptake studies of ultra
      small (30 nm) SPIONDex confirmed their internalization by macrophages, but not by
      non-phagocytic cells. Additionally, complement activation-related pseudoallergy
      (CARPA) experiments in pigs treated with ultra-small SPIONDex indicated the
      absence of hypersensitivity reactions. Conclusion: These results emphasize the
      exceptional safety of SPIONDex, setting them apart from the existing SPION-based
      contrast agents and making them a very promising candidate for further clinical
      development.

PMID- 29636609
TI  - Development of dihydrochalcone-functionalized gold nanoparticles for augmented
      antineoplastic activity.
AB  - Background: Phloridzin, an antidiabetic and antineoplastic agent usually found in
      fruit trees, is a dihydrochalcone constituent that has a clinical/pharmaceutical
      significance as a sodium-glucose linked transport 2 (SGLT2) inhibitor. While the
      aglycone metabolite of phloridzin, phloretin, displays a reduced capacity of
      SGLT2 inhibition, this nutraceutical displays enhanced antineoplastic activity in
      comparison to phloridzin. Purpose: The objective of this study was to develop
      gold nanoparticle (AuNP) mediated delivery of phloridzin and phloretin and
      explore their anticancer mechanism through conjugation of the dihydrochalcones
      and the AuNP cores. Methods: Phloridzin and phloretin conjugated AuNPs (Phl-AuNP
      and Pht-AuNP) were synthesized in single-step, rapid, biofriendly processes. The
      synthesized AuNPs morphology was characterized via transmission electron
      microscopy and ultraviolet-visible spectroscopy. The presence of phloridzin or
      phloretin was confirmed using scanning electron microscopy-energy dispersive x
      ray spectroscopy. The percentage of organic component (phloridzin/phloretin) onto
      AuNPs surface was characterized using thermogravimetric analysis. Assessment of
      the antineoplastic potency of the dihydrochalcones conjugated AuNPs against
      cancerous cell lines (HeLa) was accomplished through monitoring via flow
      cytometry. Results: The functionalized AuNPs were synthesized via a single-step
      method that relied only upon the redox potential of the conjugate itself and
      required no toxic chemicals. The synthesized Phl-AuNPs were found to be in the
      size range of 15+/-5 nm, whereas the Pht-AuNP were found to be 8+/-3 nm, placing
      both conjugated AuNPs well within the size range necessary for successful
      pharmaceutical applications. These assays demonstrate a significant increase in
      the cancerous cell toxicities as a result of the conjugation of the drugs to
      AuNPs, as indicated by the 17.45-fold increase in the efficacy of Pht-AuNPs over
      pure phloretin, and the 4.49-fold increase in efficacy of Phl-AuNP over pure
      phloridzin. Conclusion: We report a simple, biofriendly process using the
      reducing and capping potential of the dihydrochalcones, phloridzin and phloretin,
      to synthesize stable AuNPs that have promising futures as potential
      antineoplastic agents.

PMID- 29636610
TI  - Antibody-modified liposomes for tumor-targeting delivery of timosaponin AIII.
AB  - Introduction: Timosaponin AIII (TAIII), as a steroid saponin in Anemarrhena
      asphodeloides, has favorable potential as an antitumor candidate. However, its
      hydrophobicity and low bioavailability severely limit its in vivo antitumor
      efficacy. Methods: To overcome this drawback, TAIII-loaded liposomes (LP) were
      prepared to improve TAIII solubility and extend its circulation time.
      Furthermore, anti-CD44 antibody-modified LP (CD44-LP) was prepared to enhance the
      therapeutic index of TAIII. The LP and CD44-LP were also characterized through
      their biological activity, target selective binding and uptake, and in vivo
      pharmacokinetics. Results: Compared with free TAIII, both LP and CD44-LP
      possessed a desirable sustained-release profile in vitro, with ~14.2- and 10.7
      fold longer TAIII half-life, respectively, and 1.7- and 1.9-fold larger area
      under the curve, respectively. LP and CD44-LP enhanced TAIII antitumor activity
      against HepG2 cells and in a xenograft mouse model without detectable toxicity.
      In particular, CD44-LP exhibited notably higher cytotoxicity than did LP, with a
      lower half-maximal inhibitory concentration (48 h). CD44-LP exhibited stronger
      tumor inhibition, and the tumor inhibitory effect was 1.3-fold that of LP.
      Furthermore, confocal laser scanning microscopy and in vivo near-infrared imaging
      of a xenograft mouse model revealed that compared with LP, CD44-LP could
      effectively enhance tumor accumulation. Conclusion: Taken together, the results
      indicate that both CD44-LP and LP can considerably extend TAIII circulation time,
      increase tumor-targeted accumulation, and enhance antitumor activity. Thus, the
      anti-CD44 antibody-modified liposome is a promising candidate for treating CD44
      positive cancer with considerable antitumor effects.

PMID- 29636612
TI  - Correlation between cognitive impairment during the acute phase of first cerebral
      infarction and development of long-term pseudobulbar affect.
AB  - Purpose: The relationship between cognitive impairment during the acute phase of
      first cerebral infarction and the development of long-term pseudobulbar affect
      (PBA) has not been elucidated. Therefore, in this study, we aimed to determine if
      cognitive impairment during the acute phase of cerebral infarction will increase
      the risk of long-term post-infarction PBA. Patients and methods: This was a
      nested case-control study using a prospective approach. A consecutive multicenter
      matched 1:1 case-control study of cognitive impairment cases following acute
      cerebral infarction (N=26) with 26 sex-, education years-, and age-matched
      controls. Univariate and multivariate conditional logistic regression analyses
      were performed to study the clinical features and changes in cognitive domain as
      well as the risk factors for PBA. Results: Long-term PBA was independently
      predicted by low Montreal cognitive assessment (MoCA) scores at baseline.
      Multivariable regression models showed that post-infarction low MoCA scores
      remained independent predictors of long-term PBA (odds ratio [OR]=0.72; 95%
      confidence interval [CI]=0.54-0.95; P=0.018). Among all cognitive disorders,
      digit span test (DST) scores (OR=0.39; 95% CI=0.16-0.91, P=0.030), StroopC time
      (OR=1.15; 95% CI=1.01-1.31; P=0.037), and clock-drawing task (CDT) scores
      (OR=0.62; 95% CI=0.42-0.90; P=0.013) were found to be the independent risk
      factors for PBA. Conclusion: Cognitive impairment during the acute phase of
      cerebral infarction increased the risk of cerebral infarction-induced long-term
      PBA. Development of PBA was closely associated with executive function,
      attention, and visuospatial disorder.

PMID- 29636613
TI  - The acceptability of an Internet-based exposure treatment for flying phobia with
      and without therapist guidance: patients' expectations, satisfaction, treatment
      preferences, and usability.
AB  - Purpose: Internet-based treatments have been tested for several psychological
      disorders. However, few studies have directly assessed the acceptability of these
      self-applied interventions in terms of expectations, satisfaction, treatment
      preferences, and usability. Moreover, no studies provide this type of data on
      Internet-based treatment for flying phobia (FP), with or without therapist
      guidance. The aim of this study was to analyze the acceptability of an Internet
      based treatment for FP (NO-FEAR Airlines) that includes exposure scenarios
      composed of images and real sounds. A secondary aim was to compare patients'
      acceptance of two ways of delivering this treatment (with or without therapist
      guidance). Patients and methods: The sample included 46 participants from a
      randomized controlled trial who had received the self-applied intervention with
      (n = 23) or without (n = 23) therapist guidance. All participants completed an
      assessment protocol conducted online and by telephone at both pre- and
      posttreatment. Results: Results showed good expectations, satisfaction, opinion,
      and usability, regardless of the presence of therapist guidance, including low
      aversiveness levels from before to after the intervention. However, participants
      generally preferred the therapist-supported condition. Conclusion: NO-FEAR
      Airlines is a well-accepted Internet-based treatment that can help enhance the
      application of the exposure technique, improving patient acceptance and access to
      FP treatment.

PMID- 29636614
TI  - Association of high psychiatrist staffing with prolonged hospitalization, follow
      up visits, and readmission in acute psychiatric units: a retrospective cohort
      study using a nationwide claims database.
AB  - Background: The effects of psychiatrist staffing are unclear. The aim of this
      study was to assess the association of high psychiatrist staffing with prolonged
      hospitalization, follow-up visits, and readmission in acute psychiatric units.
      Methods: A retrospective cohort study was conducted using the National Database
      of Health Insurance Claim Information and Specified Medical Checkups. Patients
      newly admitted to acute psychiatric units between October 2014 and September 2015
      were followed up until September 2016. The primary exposure was a patient-to
      psychiatrist ratio of 16:1 (high-staffing units) vs 48:1 (low-staffing units).
      Outcomes were prolonged hospitalization of >90 days, number of follow-up
      psychiatric visits within 90 days after discharge, and psychiatric readmission
      within 90 days after discharge. Incidence rate ratios (IRRs) and their 95%
      confidence intervals (CIs) were estimated by using generalized estimating
      equations, adjusting for potential covariates. Results: Among the 24,678 newly
      admitted patients at 190 hospitals, 13,138 patients (53.2%) were admitted to high
      staffing units in 92 hospitals. After adjustment, high-staffing units were
      associated with a lower risk of prolonged hospitalization (incidence rate, 16.9
      vs 21.3%; IRR, 0.79 [95% CI, 0.70, 0.89]), higher number of follow-up visits
      (incidence rate of >=7 visits, 16.9 vs 13.4%; IRR, 1.06 [95% CI, 1.01, 1.12]),
      and lower risk of readmission (incidence rate, 13.0 vs 14.4%; IRR, 0.90 [95% CI,
      0.82, 0.99]). Conclusion: High-staffing units are associated with a reduced risk
      of prolonged hospitalization and readmission and an increased number of follow-up
      visits. Further research is needed to improve the generalizability of these
      findings and establish the optimal level of staffing.

PMID- 29636611
TI  - Nanomedicine applications in women's health: state of the art.
AB  - State-of-the-art applications of nanomedicine have the potential to revolutionize
      the diagnosis, prevention, and treatment of a range of conditions and diseases
      affecting women's health. In this review, we provide a synopsis of potential
      applications of nanomedicine in some of the most dominant fields of women's
      health: mental health, sexual health, reproductive medicine, oncology, menopause
      related conditions and dementia. We explore published studies arising from in
      vitro and in vivo experiments, and clinical trials where available, to reveal
      novel and highly promising therapeutic applications of nanomedicine in these
      fields. For the first time, we summarize the growing body of evidence relating to
      the use of nanomaterials as experimental tools for the detection, prevention, and
      treatment of significant diseases and conditions across the life course of a
      cisgender woman, from puberty to menopause; revealing the far-reaching and
      desirable theoretical impact of nanomedicine across different medical
      disciplines. We also present an overview of potential concerns regarding the
      therapeutic applications of nanomedicine and the factors currently restricting
      the growth of applied nanomedicine.

PMID- 29636615
TI  - Psychometric properties of the Patient Dignity Inventory in an acute psychiatric
      ward: an extension study of the preliminary validation.
AB  - Background: During the last decades, dignity has been an emerging issue in mental
      health since its ethical and therapeutic implications became known. This study is
      an extension of the preliminary validation of the Patient Dignity Inventory (PDI)
      in a psychiatric setting, originally designed for assessing perceived dignity in
      terminal cancer patients. Methods: From October 21, 2015 to December 31, 2016, we
      administered the Italian PDI to all patients hospitalized in an acute psychiatric
      ward, who provided their consent and completed it at discharge (n=165). We
      performed Cronbach's alpha coefficient and principal factor analysis. We
      administered other scales concomitantly to analyze the concurrent validity of
      PDI. We applied stepwise multiple linear regression to identify the patients'
      demographic and clinical variables related to the PDI score. Results: Our
      response rate was 93%, with excellent internal consistency (Cronbach's alpha
      coefficient=0.94). The factorial analysis showed three factors with eigenvalue
      >1, which explained >80% of total variance: 1) "loss of self-identity and anxiety
      for the future", 2) "concerns for social dignity and spiritual life", and 3)
      "loss of personal autonomy". The PDI and the three factor scores were positively
      and significantly correlated with the Hamilton Scales for Depression and Anxiety
      but not with other scale scores. Among patients' variables, "suicide risk" and
      "insufficient social and economic condition" were positively and significantly
      correlated with the PDI total score. Conclusion: The PDI can be a reliable tool
      to assess patients' dignity perception in a psychiatric setting, which suggests
      that both social and clinical severe conditions are closely related to dignity
      loss.

PMID- 29636616
TI  - Ten-year outcome of vagus nerve stimulation-implanted patients with treatment
      resistant depression: two Italian cases.
AB  - Over the last 15 years, vagus nerve stimulation (VNS) has been used as an
      augmentative therapeutic intervention in patients with treatment-resistant
      depression (TRD), whether with a lifetime diagnosis of major depressive disorder
      or bipolar disorder. From being a potentially effective treatment in the acute
      phase of TRD, recently published treatment guidelines seemed to converge on the
      indication that VNS's greatest benefit may be seen mostly beyond the short term.
      However, with the exception of a recent multicenter American report, very few
      studies have assessed the long-term efficacy of VNS in TRD patients. Herein, we
      present the cases of two Italian patients with TRD, with 10-year VNS follow-up
      evaluation. Both patients were found to benefit from augmentative VNS, and the
      latency of their stimulation response, tolerability, associated pharmacological
      treatment, number and duration of recurrences, and overall level of functioning
      are described and discussed. Further reports with larger samples are needed to
      support the long-term efficacy and tolerability of VNS in TRD patients,
      particularly beyond 5 years of follow-up.

PMID- 29636617
TI  - Investigation of variants in estrogen receptor genes and perinatal depression.
AB  - Objectives: Depressive symptoms are common during pregnancy and after childbirth.
      Estrogen levels fluctuate greatly during the course of pregnancy and may
      contribute to mood instability. The first aim of this case-control study was to
      investigate whether variants in the two estrogen receptor genes might contribute
      to the genetic susceptibility to pregnancy-related depression using controls that
      were screened for postnatal depression. The second aim was to uncover new
      variants in the two estrogen receptor genes. Patients and methods: Our study
      sample comprised 554 control subjects who had Edinburgh Postnatal Depression
      Scale (EPDS) scores below 7 at postnatal screening, and 159 patients with
      clinically diagnosed pregnancy-related depression. They were genotyped for four
      single-nucleotide polymorphisms (SNPs) and a dinucleotide repeat in the two
      genes: estrogen receptor alpha (ESR1) and estrogen receptor beta (ESR2). Fifty
      six cases with personal and/or family history of depression of psychiatric
      disorders were selected for resequencing of the two genes. Results: There was no
      statistically significant association with perinatal depression for all five
      variants. However, there was a trend toward higher frequencies of the genotypes
      associated with higher risk of depression for rs2077647 and rs4986938 in the case
      group. From resequencing, two novel ESR1 variants were identified from two
      different patients. Conclusion: Our study that used screened controls with low
      EPDS scores and cases with clinically diagnosed pregnancy-related depression
      could not replicate the association with depression for any of the SNPs for both
      genotype and allele frequencies. Two novel SNPs were identified and could be
      further investigated in a larger sample set.

PMID- 29636618
TI  - Is ischemia-modified albumin a reliable tool for the assessment of acute
      pancreatitis?
AB  - Purpose: Oxidative stress has been implicated in several disorders, including
      acute pancreatitis (AP). Ischemia-modified albumin (IMA), which reflects the
      ability to bind cobalt, has been found to be elevated in conditions of oxidative
      stress and tissue hypoxia. This study examined IMA and adjusted IMA levels in
      patients with AP, and examined the associations of IMA and adjusted IMA levels to
      the severity of AP. Patients and methods: A total of 42 consecutive patients with
      AP and 43 age- and sex-matched control subjects were enrolled. Serum samples were
      obtained from patients with AP on admission as well as 48-72 hours after
      hospitalization, and from the controls, at the time of enrollment. Adjusted IMA
      was calculated by multiplying the IMA value of each patient with the ratio of the
      patient's albumin value and the median albumin value of the study population. The
      severity of AP was assessed according to the modified Atlanta classification, and
      the patients were divided into 2 groups: mild AP and severe AP. Results: The
      serum IMA and adjusted IMA values of patients with AP on admission and those of
      the controls did not differ (p=0.86 and p=0.99, respectively). The second
      measurements of IMA and adjusted IMA in the AP group were higher than the first
      measurements of both the AP group and controls (for all, p<0.01). Among the IMA
      measurements, only adjusted IMA on admission had the ability to predict the
      severity of AP. Severe AP was correlated with albumin, and the area under the
      curve of adjusted IMA values on admission was 0.746 for differentiating patients
      with severe AP from mild AP with statistical significance (p=0.005). Conclusion:
      It was shown that IMA and adjusted IMA levels rise with the progression of AP.
      Lower levels of adjusted IMA predict the severity of AP. Further studies with
      serial measurements of IMA are warranted to explore the indicative role of IMA in
      the course of AP.

PMID- 29636619
TI  - Accommodating Grief on Twitter: An Analysis of Expressions of Grief Among Gang
      Involved Youth on Twitter Using Qualitative Analysis and Natural Language
      Processing.
AB  - There is a dearth of research investigating youths' experience of grief and
      mourning after the death of close friends or family. Even less research has
      explored the question of how youth use social media sites to engage in the
      grieving process. This study employs qualitative analysis and natural language
      processing to examine tweets that follow 2 deaths. First, we conducted a close
      textual read on a sample of tweets by Gakirah Barnes, a gang-involved teenaged
      girl in Chicago, and members of her Twitter network, over a 19-day period in 2014
      during which 2 significant deaths occurred: that of Raason "Lil B" Shaw and
      Gakirah's own death. We leverage the grief literature to understand the way
      Gakirah and her peers express thoughts, feelings, and behaviors at the time of
      these deaths. We also present and explain the rich and complex style of online
      communication among gang-involved youth, one that has been overlooked in prior
      research. Next, we overview the natural language processing output for
      expressions of loss and grief in our data set based on qualitative findings and
      present an error analysis on its output for grief. We conclude with a call for
      interdisciplinary research that analyzes online and offline behaviors to help
      understand physical and emotional violence and other problematic behaviors
      prevalent among marginalized communities.

PMID- 29636620
TI  - KIF18B promotes tumor progression through activating the Wnt/beta-catenin pathway
      in cervical cancer.
AB  - Background: KIF18B was identified as a potential oncogene by analysis of The
      Cancer Genome Atlas database. Materials and methods: We assessed KIF18B
      expression and explored its clinical significance in cervical cancer tissues. We
      have also evaluated the effects of KIF18B on cervical cancer cell proliferation,
      migration, and invasion both in vitro and in vivo. Results: Our results show that
      KIF18B is overexpressed in cervical cancer tissues and is associated with a large
      primary tumor size, an advanced FIGO stage, and an advanced tumor grade.
      Knockdown of KIF18B induces cell cycle G1-phase arrest and inhibits the
      proliferation, migration, and invasion of cervical cancer cells, whereas its
      overexpression promotes proliferation, migration, and invasion in these cells.
      Moreover, silencing of KIF18B reduces expression of CyclinD1, beta-catenin, C
      myc, and p-GSK3beta expression. Conclusion: These data suggest that KIF18B can
      serve as a novel oncogene that promotes the tumorigenicity of cervical cancer
      cells by activating Wnt/beta-catenin signaling pathway.

PMID- 29636622
TI  - miR-206 regulates 5-FU resistance by targeting Bcl-2 in colon cancer cells.
AB  - Introduction: Previous studies have found that miRNAs play a key role in drug
      resistance. Multiple reports show that miRNAs act as regulators in colorectal
      cancer (CRC) cells, but the role of miR-206 in CRC is still not well understood.
      The current study aimed to explore the potential function of miR-206 in 5-FU
      resistance. Methods: To indentify the role of miR-206 in 5-FU resistance, the
      expression of miR-206 was examined by real-time polymerase chain reaction (RT
      PCR) in 5-FU-resistant (FR) CRC (HCT116/FR and RKO/FR) and their parental cell
      lines. miR-206 mimic was transfected to 5-FU-FR CRC, and the 5-FU sensitivity was
      detected by MTS and flow cytometry. Using miRNA target prediction software, we
      found that miR-206 could target the 3' untranslated region (3'UTR) sequence of
      Bcl-2. Results: miR-206 was found to be downregulated in 5-FU-FR CRC in
      comparison with their parental cell lines, suggesting its crucial relevance for
      colon cancer biology. Downregulation of miR-206 promoted drug resistance and
      decreased apoptosis of parental cells, while overexpression of miR-206 promoted
      drug cytotoxicity and apoptosis of HCT116/FR cells. We also identified miR-206
      targeting Bcl-2 directly in CRC, which is required for miR-206 mediated-5-FU
      resistance. Conclusion: Our results show that miR-206 targets Bcl-2 to mediate
      chemoresistance, proliferation, and apoptosis in CRC. This study provides a novel
      promising candidate for colon cancer therapy.

PMID- 29636621
TI  - Antibody-sandwich ELISA analysis of a novel blood biomarker of CST4 in
      gastrointestinal cancers.
AB  - Background: Members of the cystatin family have increasingly been proven to be
      involved in several tumors, including gastric cancer (GC) and colorectal cancer
      (CRC). Cystatin S (CST4) was found to be upregulated at the gene expression level
      in GC cells, making it a potential novel biomarker for the early diagnosis of
      gastrointestinal cancer. Materials and methods: Quantitative real-time polymerase
      chain reaction and Western blotting analysis were used to explore CST4 expression
      in gastrointestinal cancer tissues and cell lines. We purified CST4 recombinant
      protein and generated anti-CST4 monoclonal antibodies to develop an antibody
      sandwich enzyme-linked immunosorbent assay (ELISA) analysis system for blood CST4
      detection. The performance and clinical efficacy of the detection method were
      evaluated using a training set and validation set, respectively. Results:
      According to the quantitative real-time polymerase chain reaction and Western
      blotting results, CST4-mRNA expression and protein expression were upregulated in
      gastrointestinal cancer tissues and cell lines. The ELISA detection system for
      CST4 showed significantly better sensitivities of 69.0% and 69.0% and
      specificities of 85.6% and 83.6% for GC and CRC, respectively, than other common
      clinical biomarkers, carcinoembryonic antigen, CA19-9, CA125, and CA72-4.
      Clinical verification experiments using GC and CRC validation sets also found
      distinguishable CST4 median concentrations (177.7 pg.mL-1 and 174.2 pg.mL-1
      respectively) and high positive detection rates (72.3% and 88.4% respectively),
      further confirming the specificity and sensitivity of this method. Conclusion: We
      validated the overexpression of CST4 in gastrointestinal cancer tissues and cell
      lines and developed an antibody-sandwich ELISA analysis system for blood CST4
      detection, which exhibited high specificity and sensitivity. Novel blood
      biomarkers of CST4 have enormous potential in terms of clinical diagnostic value
      in GC and CRC.

PMID- 29636623
TI  - Synergistic antitumor effects of tanshinone IIA and sorafenib or its derivative
      SC-1 in hepatocellular carcinoma cells.
AB  - Introduction: Hepatocellular carcinoma (HCC) is the most common form of hepatic
      malignancy in the world. We aimed to determine the effect of tanshinone IIA (Tan
      IIA) in combination with sorafenib or its derivative SC-1 on cytotoxicity,
      apoptosis, and metastasis in human HCC cells. Materials and methods: Cytotoxicity
      was detected by MTT assay. Apoptosis and sub-G1 populations were analyzed by flow
      cytometry. Cell migration and invasion were evaluated by Transwell assay. Protein
      expression was detected by Western blot. Results: Tan-IIA combined with sorafenib
      or SC-1 exerted synergistic cytotoxicity in HCC cells. Elevated proportions of
      sub-G1 and caspase activation were observed in the combinative treatments; in
      addition, marked inhibition of cell migration and invasion, which could be
      mediated by the modulation of epithelial-mesenchymal transition was observed.
      pSTAT3 levels were significantly reduced as well. Conclusion: A combination
      therapy using Tan-IIA and sorafenib or SC-1 could be a promising approach to
      target HCC, and further preclinical investigations are warranted to establish
      their synergetic advantage.

PMID- 29636624
TI  - Prognostic value of increased integrin-beta 1 expression in solid cancers: a meta
      analysis.
AB  - Integrin-beta 1 (ITGB1) is aberrantly overexpressed or downregulated in solid
      cancers; however, its prognostic value remains controversial. Therefore, we
      conducted a meta-analysis to explore whether ITGB1 expression is correlated with
      overall survival (OS) and the clinicopathological characteristics of patients
      with solid cancers. We systematically searched the PubMed, Embase, and Web of
      Science databases for eligible studies published up to June 1, 2017. In total, 22
      studies involving 3,666 patients were included. A sensitivity analysis was
      performed to assess the validity and reliability of the pooled OS. Among the 22
      studies, 7 focused on lung cancer, 3 focused on colorectal cancer, 6 focused on
      breast cancer, 3 involved melanoma, and 3 involved pancreatic cancer. The pooled
      results showed that high ITGB1 expression was significantly associated with worse
      OS in lung cancer (pooled hazard ratio [HR]=1.78, 95% CI: 1.19-2.65, p<0.05) and
      breast cancer (pooled HR=1.88, 95% CI: 1.46-2.42, p<0.01). In addition, a
      significant association was observed between high ITGB1 expression and disease
      free survival in breast cancer (pooled HR=1.63, 95% CI: 1.17-2.25, p<0.001) and
      pancreatic cancer (pooled HR=2.49, 95% CI: 1.35-4.61, p<0.001). However, high
      ITGB1 expression was not related to OS in colorectal cancer, pancreatic cancer,
      or melanoma. The pooled HRs used to evaluate the prognostic value of increased
      ITGB1 expression in lung cancer, breast cancer, and pancreatic cancer were not
      significantly altered, which indicates that the pooled results were robust. The
      results of this study indicate that the prognostic value of decreased ITGB1
      expression varies among solid cancers.

PMID- 29636625
TI  - Overproduction of efflux pumps caused reduced susceptibility to carbapenem under
      consecutive imipenem-selected stress in Acinetobacter baumannii.
AB  - Purpose: Acinetobacter baumannii is an important pathogen in the nosocomial
      infections worldwide. Combining with carbapenemases, efflux pumps and outer
      membrane proteins (OMPs) have been thought to affect the development of
      carbapenem resistance in A. baumannii. This study aimed to investigate the
      contributions of different efflux pumps and OMPs in developing carbapenem
      resistance in a clinical isolate of A. baumannii and reveal the possible
      mechanism of overproduction of main efflux pumps. Patients and methods: In this
      study, an imipenem-susceptible clinical isolate was identified as A. baumannii
      and named SZE. Several common carbapenemases were detected by polymerase chain
      reaction (PCR). Imipenem-selected mutants were selected from SZE by serial
      subcultivations on Mueller-Hinton agar, and the minimum inhibitory concentration
      (MIC) was detected. Gene expressions of four families of efflux pumps, five OMPs,
      and blaOXA-51 were determined by reverse transcription quantitative PCR, and
      comparisons were made between SZE strain and the imipenem-selected mutants. The
      adeRS system in SZE and its mutant was sequenced and aligned. Results: Under
      consecutive imipenem-selected stress, the MIC to imipenem increased gradually
      from 0.125 MUg/mL to 8 MUg/mL. The effect of resistance inducement was almost
      neutralized when treated with an efflux pump inhibitor. The expression of efflux
      pumps, adeB, adeG, and adeJ, was increased by 6.9-, 4.0-, and 2.1-fold in
      mutants, respectively, compared to SZE. A single mutation (G to A) at position 58
      was detected in the regulatory adeRS system and possibly upregulated the adeB
      expression, and then affected the carbapenem resistance in A. baumannii strains.
      Conclusion: In conclusion, under consecutive imipenem-selected stress in vitro,
      A. baumannii strain evolved the ability to reduce susceptibility to a variety of
      antimicrobials by overproduction of efflux pumps. Especially, the resistance
      nodulation-cell division super family and a nucleotide mutant in adeRS regulating
      system caused the overexpression of adeABC.

PMID- 29636626
TI  - Factors associated with adherence to diabetes care recommendations among children
      and adolescents with type 1 diabetes: a facility-based study in two urban
      diabetes clinics in Uganda.
AB  - Purpose: The purpose of this study was to determine the level of adherence and
      the factors associated with adherence to diabetes care recommendations among type
      1 diabetic children and adolescents at two urban diabetes clinics in Kampala,
      Uganda. Research design and methods: A facility-based cross-sectional study was
      carried out among 200 children and adolescents with type 1 diabetes at two major
      diabetes clinics in Kampala. Caretakers of the children and adolescents were
      interviewed using pretested questionnaires to provide information on
      sociodemographic characteristics, diabetes care, knowledge, attitudes, and
      adherence to diabetes care recommendations in type 1 diabetes. Prevalence rate
      ratios (PRRs) at the 95% confidence interval (CI) were used to establish the
      factors associated with adherence using modified Poisson regression, with robust
      standard errors. The data were analyzed by using STATA Version 13.0. Results: The
      overall prevalence of adherence to diabetes care recommendations was at 37%.
      However, evaluating adherence to specific treatment parameters showed that 52%,
      76.5%, and 29.5% of the children and adolescents adhered to insulin, blood
      glucose monitoring, and dietary recommendations, respectively. In the final
      adjusted model, active diet monitoring (adjusted PRR [APRR]: 1.95; 95% CI: 1.01,
      3.78), being under care of a sibling (APRR: 1.66; 95% CI: 1.61, 1.71), being
      under care of a married caretaker (APRR: 1.10; 95% CI: 1.05, 1.14) and a
      separated or divorced caretaker (APRR: 1.60; 95% CI: 1.12, 2.27), taking three or
      less tests of blood glucose per day (APRR: 0.63; 95% CI: 0.42, 0.95), and having
      a caretaker with poor knowledge about diabetes (APRR: 0.49; 95% CI: 0.43, 0.57)
      and who is inactive in supervision of insulin injections (APRR: 0.58; 95% CI:
      0.56, 0.60) were associated with adherence to type 1 diabetes care
      recommendations. Conclusion: Adherence to type 1 diabetes care recommendations is
      still low among this population. The results suggest that reinforcing caretaker
      involvement could be vital in improving adherence to diabetes care
      recommendations in this population.

PMID- 29636627
TI  - A meta-analysis of cyclosporine treatment for Stevens-Johnson syndrome/toxic
      epidermal necrolysis.
AB  - Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)
      are dermatologic emergencies with high morbidity and mortality risk.
      Cyclosporine, an immunomodulatory agent, is sometimes used off-label, and its
      role continues to be debated. This meta-analysis aimed to provide an update of
      current evidence and to clarify the role of cyclosporine in SJS/TEN treatment
      better. Methods: Using the keywords [cyclosporine OR cyclosporine OR ciclosporin
      OR CsA] AND [Steven-Johnson OR SJS OR toxic epidermal OR epidermal necrolysis OR
      TEN OR hypersensitivity OR dermatologic OR burns], a preliminary search on the
      PubMed, Ovid, Web of Science, and Google Scholar Database yielded 615 papers
      published in English between January1, 1960 and July 1, 2017. The inclusion
      criteria for this review were: 1) published retrospective or prospective study
      (excluding single case reports); 2) patients with clinical diagnosis of SJS or
      TEN; 3) trial of cyclosporine treatment; and 4) available survival/mortality
      data. Results: A total of 12 studies, with a total of 358 SJS/TEN patients were
      reviewed. Two studies were excluded from the meta-analysis as they did not report
      SCORe of toxic epidermal necrosis/predicted mortality data; one was excluded
      because of possible data irregularities. Meta-analysis of nine studies revealed a
      significant reduction in mortality risk with cyclosporine therapy (standardized
      mortality ratio 0.320; 95% CI: 0.119-0.522; P=0.002). Cyclosporine was also
      generally well tolerated with little adverse effects or increased infection,
      albeit the patients tended to be critically ill. Publication bias was observed in
      the funnel plot and Egger test (P=0.0467). Conclusion: Currently available
      evidence are predominantly open trials and retrospective studies with a
      significant risk of bias, perhaps owing to the rarity and life-threatening nature
      of the condition. Given its immunomodulatory actions, cyclosporine could be a
      potential treatment option for SJS/TEN in addition to best supportive measures.
      Further confirmation with robust randomized, controlled trials or larger case
      series is necessary and should be encouraged.

PMID- 29636628
TI  - CYP2C9 polymorphisms in epilepsy: influence on phenytoin treatment.
AB  - Phenytoin (PHT) is an antiepileptic drug widely used in the treatment of focal
      epilepsy and status epilepticus, and effective in controlling focal seizures with
      and without tonic-clonic generalization and status epilepticus. The
      metabolization of PHT is carried out by two oxidative cytochrome P450 enzymes
      CYP2C9 and CYP2C19; 90% of this metabolization is done by CYP2C9 and the
      remaining 10% by CYP2C19. Genetic polymorphism of CYP2C9 may reduce the
      metabolism of PHT by 25-50% in patients with variants *2 and *3 compared to those
      with wild-type variant *1. The frequency distribution of CYP2C9 polymorphism
      alleles in patients with epilepsy around the world ranges from 4.5 to 13.6%,
      being less frequent in African-Americans and Asians. PHT has a narrow therapeutic
      range and a nonlinear pharmacokinetic profile; hence, its poor metabolization has
      significant clinical implications as it causes more frequent and more serious
      adverse effects requiring discontinuation of treatment, even if it had been
      effective. There is evidence that polymorphisms of CYP2C9 and the use of PHT are
      associated with an increase in the frequency of some side effects, such as
      cerebellar atrophy, gingival hypertrophy or acute cutaneous reactions. The
      presence of HLA-B*15:02 and CYP2C9 *2 or *3 in the same patient increases the
      risk of Stevens-Johnson syndrome and toxic epidermal necrolysis; hence, PHT
      should not be prescribed in these patients. In patients with CYP2C9 *1/*2 or
      *1/*3 alleles (intermediate metabolizers), the usual PHT maintenance dose (5-10
      mg/kg/day) must be reduced by 25%, and in those with CYP2C9 *2/*2, *2/*3 or *3/*3
      alleles (poor metabolizers), the dose must be reduced by 50%. It is controversial
      whether CYP2C9 genotyping should be done before starting PHT treatment. In this
      paper, we aim to review the influence of CYP2C9 polymorphism on the
      metabolization of PHT and the clinical implications of poor metabolization in the
      treatment of epilepsies.

PMID- 29636629
TI  - Late-life depression: issues for the general practitioner.
AB  - Late-life depression (LLD) is both a prevalent and life-threatening disorder,
      affecting up to 13.3% of the elderly population. LLD can be difficult to identify
      because patients mainly consult their general practitioner (GP) for somatic
      complaints. Moreover, patients may be hesitant to express the problem to their
      GP. Increased vigilance on the part of the GP can only benefit older people with
      depression. To recognize the risk of LLD, screening tools are provided in
      addition to treatment options for LLD. This review aims to provide the GP with
      guidance in recognizing and treating LLD. It tries to connect mainstream
      etiologies of LLD (e.g., vascular, inflammation, hypothalamo-pituitary-adrenal
      axis) with risk factors and current therapies. Therefore, we provide a basis to
      the GP for decision-making when choosing an appropriate therapy for LLD.

PMID- 29636631
TI  - beta-Guanidinopropionic Acid Stimulates Brain Mitochondria Biogenesis and Alters
      Cognitive Behavior in Nondiseased Mid-Age Mice.
AB  - beta-guanidinopropionic acid (beta-GPA) has been used as a nutritional supplement
      for increasing physical strength and endurance with positive and predictable
      results. In muscles, it works as a nonadaptive stimulator of mitochondria
      biogenesis; it also increases lipid metabolism. There are data indicating that
      beta-GPA can be also neuroprotective, but its mechanisms of action in the brain
      are less understood. We studied the effects of beta-GPA on animal behavior and
      mitochondrial biogenesis in the cortex and midbrain of mid-age healthy mice. We
      found that even short-term 3-week-long beta-GPA treatment increased the
      mitochondrial DNA (mtDNA) copy number in the cortex and ventral midbrain, as well
      as the expression of several key antioxidant and metabolic enzymes-indicators of
      mitochondria proliferation and the activation of Nrf2/ARE signaling cascade. At
      the same time, beta-GPA downregulated the expression of the beta-oxidation genes.
      Administration of beta-GPA in mice for 3 weeks improved the animals' physical
      strength and endurance health, ie, increased their physical strength and
      endurance and alleviated anxiety. Thus, beta-GPA might be considered an
      adaptogene affecting both the muscle and brain metabolism in mammals.

PMID- 29636630
TI  - The impact of anxiety and catastrophizing on interleukin-6 responses to acute
      painful stress.
AB  - Objective: To examine the influence of anxiety and pain-related catastrophizing
      on the time course of acute interleukin-6 (IL-6) responses to standardized
      noxious stimulation among patients with chronic pain. Methods: Data were
      collected from 48 participants in the following demographically matched groups:
      patients with chronic pain (n=36) and healthy controls (n=12). Participants
      underwent a series of Quantitative Sensory Testing (QST) procedures assessing
      responses to mechanical and thermal stimuli during two separate visits, in a
      randomized order. One visit consisted of standard, moderately painful QST
      procedures, while the other visit involved nonpainful analogs to these testing
      procedures. Blood samples were taken at baseline, and then for up to 2 hours
      after QST in order to study the time course of IL-6 responses. Results: Results
      of multilevel analyses revealed that IL-6 responses increased across assessment
      time points in both visits (p<0.001). While patients with chronic pain and
      healthy controls did not differ in the magnitude of IL-6 responses, psychological
      factors influenced IL-6 trajectories only in the chronic pain group. Among
      patients, increases in catastrophizing over the course of the QST session were
      associated with elevated IL-6 responses only during the painful QST session
      (p<0.05). When controlling for anxiety, results indicated that the main
      multilevel model among patients remained significant (p<0.05). Conclusion: Under
      specific conditions (eg, application of a painful stressor), catastrophizing may
      be associated with amplified proinflammatory responses in patients with
      persistent pain. These findings suggest that psychosocial interventions that
      reduce negative pain-related cognitions may benefit patients' inflammatory
      profiles.

PMID- 29636632
TI  - AP2gamma: A New Player on Adult Hippocampal Neurogenesis Regulation.
AB  - Since the recognition that the mammalian brain retains the ability to generate
      newborn neurons with functional relevance throughout life, the matrix of
      molecular regulators that govern adult neurogenesis has been the focus of much
      interest. In a recent study published in Molecular Psychiatry, we demonstrate
      Activating Protein 2gamma (AP2gamma), a transcription factor previously
      implicated in cell fate determination in the developing cortex, as a novel player
      in the regulation of glutamatergic neurogenesis in the adult hippocampus. Using
      distinct experimental approaches, we showed that AP2gamma is specifically present
      in a subpopulation of transient amplifying progenitors, where it acts as a
      crucial promoter of proliferation and differentiation of adult-born glutamatergic
      granule neurons. Strikingly, deficiency of AP2gamma in the adult brain
      compromises the generation of new glutamatergic neurons, with impact on the
      function of cortico-limbic circuits. Here, we share our view on how AP2gamma
      integrates the transcriptional orchestration of glutamatergic neurogenesis in the
      adult hippocampus, and consequently, how it emerges as a novel molecular
      candidate to study the translation of environmental pressures into alterations of
      brain neuroplasticity in homeostatic, but also in neuropathological contexts.

PMID- 29636633
TI  - Why was this transfusion given? Identifying clinical indications for blood
      transfusion in health care data.
AB  - Background: To enhance the utility of transfusion data for research, ideally
      every transfusion should be linked to a primary clinical indication. In
      electronic patient records, many diagnostic and procedural codes are registered,
      but unfortunately, it is usually not specified which one is the reason for
      transfusion. Therefore, a method is needed to determine the most likely
      indication for transfusion in an automated way. Study design and methods: An
      algorithm to identify the most likely transfusion indication was developed and
      evaluated against a gold standard based on the review of medical records for 234
      cases by 2 experts. In a second step, information on misclassification was used
      to fine-tune the initial algorithm. The adapted algorithm predicts, out of all
      data available, the most likely indication for transfusion using information on
      medical specialism, surgical procedures, and diagnosis and procedure dates
      relative to the transfusion date. Results: The adapted algorithm was able to
      predict 74.4% of indications in the sample correctly (extrapolated to the full
      data set 75.5%). A kappa score, which corrects for the number of options to
      choose from, was found of 0.63. This indicates that the algorithm performs
      substantially better than chance level. Conclusion: It is possible to use an
      automated algorithm to predict the indication for transfusion in terms of
      procedures and/or diagnoses. Before implementation of the algorithm in other data
      sets, the obtained results should be externally validated in an independent
      hospital data set.

PMID- 29636635
TI  - Comprehensive Evaluation of Commercial Bisulfite-Based DNA Methylation Kits and
      Development of an Alternative Protocol With Improved Conversion Performance.
AB  - DNA methylation is the most studied epigenetic modification with a wide range of
      regulatory functions in mammalian genomes. It almost exclusively resides on CpG
      dinucleotides and, among others, plays important roles in early embryo
      development, onset, and maintenance of cancer. During the past 3 decades, many
      approaches have been developed to discriminate methylated from unmethylated DNA
      including antibody-based enrichment of methylated DNA, restriction enzyme-based,
      or hybridization-based methods. The conversion of unmethylated cytosines to
      uracils by sodium or ammonium bisulfite is regarded as golden standard as this
      approach requires no enzymatic reaction and provides deep and reliable insight in
      methylation patterns at single-base resolution. Nowadays, there are many
      commercial kits for bisulfite conversion available but they perform differently
      and also vary in protocols and chemicals used. Here, we provide the first
      comprehensive and comparative evaluation of bisulfite conversion kits observing
      major differences in conversion efficiency and DNA degradation which greatly
      affect the performance of downstream applications, ie, polymerase chain reactions
      (PCRs). Moreover, deep sequencing of amplicons containing oxidized derivates of
      5'-methylC shows that none of the tested kits efficiently converts 5'-formylC
      without substantial conversion of 5'-methylC or 5'-hydroxymethylC. Consequently,
      we developed a robust and easy-to-use protocol that allows maximal discrimination
      between 5'-formylC and 5'-methylC/5'-hydroxymethylC with low DNA degradation and
      high PCR efficiency on the bisulfite-treated DNA. We highly recommend to use our
      time- and cost-efficient protocol for any genome-wide or local high-resolution
      bisulfite sequencing application to minimize conversion-dependent error rates.

PMID- 29636634
TI  - Triptych of the Hermit Saints: pneumococcal polysaccharide vaccines for the
      elderly.
AB  - Pneumococcal pneumonia is a serious disease with considerable morbidity and
      mortality in the elderly. Despite adequate antibiotic treatment, the long-term
      mortality of pneumococcal pneumonia remains high. Preventive measures in the form
      of vaccination, therefore, are warranted. Twenty-three-valent polysaccharide
      vaccines have a broad coverage but limited efficacy. Pneumococcal conjugate
      vaccines have been shown in children to be able to prevent invasive and mucosal
      pneumococcal diseases. It should be realized that the serotype composition of
      current pneumococcal conjugate vaccines is not tailored for the elderly, and that
      replacement disease can occur. Yet, the current 13-valent conjugate vaccine has
      been shown to protect against infections with vaccine serotypes. Long-term
      mortality of pneumococcal pneumonia should be included in policy making about the
      introduction of these vaccines for the elderly.

PMID- 29636636
TI  - Effects of Varying Photoperiodic Regimens on Critical Biological Fitness Traits
      of Culex quinquefasciatus (Diptera: Culicidae) Mosquito Vector.
AB  - This study investigated the effects of varying photoperiodic conditions on
      critical life stages' parameters of Culex quinquefasciatus. To this end, first
      larval stage was reared under different constant photoperiodic regimens: 0, 6
      (short), 12 (equal), 13 (prevailing condition), and 18 and 24 (long) hours of
      light (hL). Duration of development, survivorship, emergence successes, adult
      longevity, caloric indices (CIs), and utilisation of teneral reserves for
      metamorphosis at each regimen were monitored. Analyses revealed significant
      negative effects of increasing photoperiod on all entomological variables
      measured. Short photo-phases elicited faster development times, increased life
      stages' survivorship and number at emergence, adult longevity, and CI for all
      life stages while increasing teneral components for adult life traits. The
      information generated in this study is important in understanding the role played
      by photoperiod in disease transmission and for development of integrated vector
      control strategies based on environmental manipulation.

PMID- 29636638
TI  - It is time to improve the quality of medical information distributed to students
      across social media.
AB  - The ubiquitous nature of social media has meant that its effects on fields
      outside of social communication have begun to be felt. The generation undergoing
      medical education are of the generation referred to as "digital natives", and as
      such routinely incorporate social media into their education. Social media's
      incorporation into medical education includes its use as a platform to distribute
      information to the public ("distributive education") and as a platform to provide
      information to a specific audience ("push education"). These functions have
      proved beneficial in many regards, such as enabling constant access to the
      subject matter, other learners, and educators. However, the usefulness of using
      social media as part of medical education is limited by the vast quantities of
      poor quality information and the time required to find information of sufficient
      quality and relevance, a problem confounded by many student's preoccupation with
      "efficient" learning. In this Perspective, the authors discuss whether social
      media has proved useful as a tool for medical education. The current growth in
      the use of social media as a tool for medical education seems to be principally
      supported by students' desire for efficient learning rather than by the efficacy
      of social media as a resource for medical education. Therefore, improvements in
      the quality of information required to maximize the impact of social media as a
      tool for medical education are required. Suggested improvements include an
      increase in the amount of educational content distributed on social media
      produced by academic institutions, such as universities and journals.

PMID- 29636637
TI  - Pancreatitis Is a Silent Killer in Peritoneal Dialysis With Difficult Diagnostic
      Approach.
AB  - Until 2018, 236 cases of acute pancreatitis have been reported in patients who
      underwent peritoneal dialysis. Here, we presented a patient with double renal
      transplantation with chronic renal failure, under renal replacement therapy by
      peritoneal dialysis, who developed acute pancreatitis with abdominal pain,
      nausea, vomiting, leukocytosis with neutrophil left shift which is complicated by
      pancreatic pseudocyst, candida peritonitis, fungal sepsis, overlapping of
      Acinetobacter baumannii sepsis, and pneumonitis. After the percutaneous
      cystogastrostomy drainage of pancreatic pseudocyst, changes from peritoneal
      dialysis to hemodialysis, various thoracentesis, and polyantibiotics therapy, the
      resolution of the sepsis state was seen. The particular aspect of our case is the
      various comorbidity risks, severe pancreatitis associated with candida and A
      baumannii sepsis, and treatment strategy that lead to heal this kind of the high
      mortality rate condition.

PMID- 29636639
TI  - A pilot study to assess short-term physiologic outcomes of transitioning infants
      with severe bronchopulmonary dysplasia from ICU to two subacute ventilators.
AB  - Introduction: This study was designed to evaluate short-term physiologic outcomes
      of transitioning neonates with bronchopulmonary dysplasia (BPD) from intensive
      care unit (ICU) ventilators to both the Trilogy 202 (Philips Healthcare, Andover,
      MA) and LTV 1200 (CareFusion, Yorba Linda, CA) subacute ventilators. Methods: Six
      infants with BPD requiring tracheostomies for support with a neonatal-specific
      ICU ventilator underwent placement of esophageal balloon catheters, airway
      pressure transducers, flow sensors, oxygen saturation (SpO2), and end tidal
      carbon dioxide (PETCO2) monitors. Noninvasive gas exchange, airflow, and airway
      and esophageal pressures (PES) were recorded following 20 min on the ICU
      ventilator. The infants were placed on the Trilogy 202 and LTV 1200 ventilators
      in random order at identical settings as the ICU ventilator. We measured
      noninvasive gas exchange, pressure-rate product (respiratory rate * DeltaPES),
      ventilator response times, and the percentage of spontaneous breaths that
      triggered the ventilator at 20 min in each subject while being supported with
      each of the different subacute ventilators. Results: The mean (SD) weight of the
      six infants was 4.983 (0.56) kg. There were no differences in heart rate (p =
      0.51) or SpO2 (p = 0.97) but lower PETCO2, DeltaPES, respiratory rate, pressure
      rate-product, response times, and greater percentage of subject initiated breaths
      that triggered the ventilator (p < 0.05) was observed with the Trilogy 202 than
      the LTV 1200. All six infants transitioned successfully from the ICU ventilator
      to the Trilogy 202 ventilator. Conclusion: In this small group of infants with
      BPD, the Trilogy 202 ventilator performed better than the LTV 1200. The improved
      subject efforts, per cent subject triggering, and response times observed with
      the Trilogy are likely related to differences in triggering algorithms, location
      of triggering mechanisms, and gas delivery system performance within the
      ventilators. These pilot data may be useful for informing future clinical study
      design and understanding differences in the level of support provided by
      different subacute ventilators in infants with BPD.

PMID- 29636641
TI  - Down-regulation of STAT3 induces the apoptosis and G1 cell cycle arrest in
      esophageal carcinoma ECA109 cells.
AB  - Background: Signal transducer and activator of transcription 3 (STAT3) is
      persistently activated in a wide variety of epithelial cancers. Aberrant activity
      of STAT3 correlates with tumor growth, invasion and metastasis, which makes it a
      potential therapeutic target of cancer. To explore the biological role of STAT3
      in esophageal cancer, we used small hairpin RNA to knockdown the expression of
      the STAT3 gene in the esophageal carcinoma ECA109 cell line and the cell
      apoptosis, cell cycle and cell migration were investigated. Methods: The cell
      apoptosis was tested using DNA ladder, mitochondrial membrane potential assay,
      TUNEL assay, annexin V-PI staining. Cell cycle phases were estimated using flow
      cytometry analysis. The mRNA and proteins related to apoptosis and cell cycle
      were examined by quantitative real-time polymerase chain reaction (qRT-PCR) and
      Western blot, respectively. And cell migration was investigated by in vitro
      Transwell assay. The data were analyzed with two-sample Student's t test and
      ANOVA followed by the LSD post hoc test. Results: Our results showed that
      knockdown of STAT3 in ECA109 cells induced noticeable apoptotic morphological
      changes like cell shrinkage, apoptotic vacuoles, membrane blebbing time
      dependently. In addition, DNA ladder, TUNEL assay, Annexin V-PI staining and
      declined level of cleaved Caspase-3 indicated that down-regulation of STAT3 could
      induce apoptosis in ECA109 cells. Flow cytometry analysis displayed the induction
      of G1-phase cell cycle arrest of ECA109 cells by STAT3 decreasing, consistent
      with the descend of c-Myc and cyclin D1 in protein levels. Furthermore, STAT3
      knockdown suppressed the expression of matrix metalloproteinases-9, sushi domain
      containing 2 and urokinase plasminogen activator in ECA109 cells and inhibited
      cell migration ability. Conclusions: Knockdown of STAT3 could induce the
      apoptosis and G1 cell cycle arrest in esophageal carcinoma ECA109 cells, and
      inhibit the migration ability of cells as well.

PMID- 29636640
TI  - MiR-544 promotes immune escape through downregulation of NCR1/NKp46 via targeting
      RUNX3 in liver cancer.
AB  - Objective: To study the potential role of miR-544 in the immune escape mechanism
      of hepatoma cells. Methods: Natural killer (NK) cells were collected from healthy
      volunteers and patients with liver cancer. Interleukin (IL)-2 activated-NK-92
      cells were transfected with miR-544 inhibitor/mimic or NC/pre-NC in HepG2 co
      culture system. NK-92 cells were treated with control, IL-2, IL-2 + pre-NC, IL-2
      + miR-544 mimic, IL-2 + miR-544 mimic + pcDNA and IL-2 + miR-544 mimic + pcDNA
      runt-related transcription factor 3 (RUNX3) groups. Mice models of liver cancer
      were well established. Expression of miR-544, natural cytotoxicity receptor 1
      (NCR1) and RUNX3 were evaluated by quantitative real-time PCR and western
      blotting. Flow cytometry and ELISA were used to determine NK cell cytotoxicity
      and the levels of INF-gamma, respectively. Results: MiR-544 was upregulated while
      NCR1 and RUNX3 was downregulated in NK cells of patients with liver cancer. The
      levels of IFN-gamma and miR-544 expression were increased and decreased in IL-2
      activated-NK cells, respectively. Inversely, miR-544 overexpression inhibited NK
      cell cytotoxicity by downregulating IFN-gamma. However, miR-544 directly targeted
      RUNX3 and negatively regulated NCR1. Furthermore, miR-544 promoted immune escape
      of hepatoma cells in vivo and in vitro. Conclusion: miR-544 promoted the immune
      escape of liver cancer cells by downregulating NCR1 via targeting RUNX3.

PMID- 29636642
TI  - Correction to: Knockdown of miR-155 protects microglia against LPS-induced
      inflammatory injury via targeting RACK1: a novel research for intracranial
      infection.
AB  - [This corrects the article DOI: 10.1186/s12950-017-0162-7.].

PMID- 29636643
TI  - Functional role of microRNA-135a in colitis.
AB  - Background: Inflammatory bowel disease (IBD) is one of the chronic
      gastrointestinal diseases with increasing risk of colon cancer development in the
      future. Apoptosis and inflammation play an important role in the etiology of this
      disease. MicroRNAs are associated with etiology of different diseases including
      IBD. In this study, we aimed to explore the role of miR-135a in the etiology of
      colitis in murine model of DSS-induced colitis. Results: The results showed that
      expression of miR-135a in colonic cells was suppressed and up-regulating miR-135a
      inhibited apoptosis and inflammation of colonic epithelial cells. Additionally,
      Hif1alpha was identified as the target gene of miR-135a which promoted apoptosis
      and inflammation as knockdown of Hif1alpha led to the suppression of both
      apoptosis and inflammation. Conclusions: Overexpression of miR-135a might be
      beneficial in IBD due to its anti-apoptosis and anti-inflammation effects in
      vitro.

PMID- 29636645
TI  - Edward I. Chang, MD, FACS, Mark V. Schaverien, MBChB, MD, MSc, MEd, FRCS (Plast),
      Jesse C. Selber, MD, MPH, FACS.

PMID- 29636644
TI  - Combined life-threatening thromboses and hemorrhages in a patient with
      afibrinogenemia and antithrombin deficiency.
AB  - Background: Patients with congenital afibrinogenemia suffer from spontaneous
      recurrent severe bleeding. While fibrinogen concentrates are known to effectively
      treat bleeding episodes, thrombotic complications often occur upon replacement
      therapy, rendering clinical management highly challenging. Case Presentation: We
      hereby report a case of combined afibrinogenemia and congenital antithrombin
      deficiency manifested by recurrent life-threatening bleeding, as well as
      spontaneous severe arterial occlusion, such as acute coronary syndrome and
      stroke, and venous thromboses like pulmonary embolism.Secondary fibrinogen
      prophylaxis is recommended following any initial life-threatening bleeding
      episode in patients with afibrinogenemia, yet the high associated risk of
      thrombosis illustrates the complexity of choosing the most effective prophylaxis
      strategy combining fibrinogen concentrate with antithrombotic agent for optimal
      protection against the risk of both severe bleeding and thrombosis. For our
      patient, the thrombin generation assay objectively confirmed her prothrombotic
      tendency. Conclusion: This case may help us better understand the pathophysiology
      of arterial thrombosis in afibrinogenemia, while highlighting the difficulty of
      managing such complications.

PMID- 29636646
TI  - Lymphedema Management.

PMID- 29636647
TI  - Anatomy of the Lymphatic System and the Lymphosome Concept with Reference to
      Lymphedema.
AB  - Precise knowledge of the lymphatic system normal anatomy is essential for
      understanding what structural changes occur in patients with lymphedema. In this
      article, the authors first review previous anatomical studies and summarize the
      general anatomy of the lymphatic system and lymphatic pathways in the upper and
      lower extremities. Second, they introduce their new anatomical concept, the
      "lymphosome," which describes how the lymphatic vessels in a particular region
      connect to the same subgroup of regional lymph nodes. In addition, they describe
      the anatomical relationship between the perforating lymphatic vessels and
      arteries. In the last section, they explain the anatomical changes in the
      lymphatics after lymph node dissection, with reference to secondary lymphedema.

PMID- 29636648
TI  - Diagnosis and Staging of Lymphedema.
AB  - Lymphedema often is confused with other causes of extremity edema and
      enlargement. Understanding the risk factors and physical examination signs of
      lymphedema can enable the health care practitioner to accurately diagnose
      patients ~90% of the time. Confirmatory diagnosis of the disease is made using
      lymphoscintigraphy. It is important to correctly diagnose patients with
      lymphedema so that they can be managed appropriately.

PMID- 29636649
TI  - Nonoperative Treatment of Lymphedema.
AB  - Complex decongestive therapy is the mainstay of lymphedema (LE) therapy. It
      consists of two phases: an intensive volume reduction phase, principally
      involving low-stretch bandages and manual lymph drainage (MLD), followed by
      compression garment use to maintain the reduction achieved. Adjunctive treatments
      include the use of a sequential gradient pump, LE-specific exercises, skin and
      nail care, as well as risk-reduction precautions. Herein the techniques are
      described and the evidence for their effectiveness is reviewed.

PMID- 29636650
TI  - Lymphovenous Anastomosis Bypass Surgery.
AB  - The field of lymphedema surgery has witnessed tremendous advancements over the
      years and has been coupled to the rapid growth of supermicrosurgical techniques.
      A lymphovenous bypass or lymphaticovenular anastomosis is a new technique that
      requires identification of patent, residual lymphatic channels and performing an
      anastomosis to a recipient venule, thereby allowing outflow of lymphatic fluid
      and improvement in a patient's lymphedema. This article provides a summary of the
      maturation of the technique, as well as the technical aspects of the approach and
      the current outcomes in the treatment of postmastectomy lymphedema.

PMID- 29636651
TI  - Vascularized Lymph Node Transfer for Lymphedema.
AB  - Advances in our understanding of the lymphatic system and the pathogenesis of
      lymphedema have resulted in the development of effective surgical treatments.
      Vascularized lymph node transfer (VLNT) involves the microvascular
      transplantation of functional lymph nodes into an extremity to restore
      physiological lymphatic function. It is most commonly performed by transferring
      combined deep inferior epigastric artery perforator and superficial inguinal
      lymph node flaps for postmastectomy breast reconstruction. For patients who do
      not require or are unable to undergo free abdominal breast reconstruction or have
      lymphedema affecting the lower extremity, several other VLNT options are
      available. These include flaps harvested from within the axillary, inguinal, or
      cervical lymph node basins, and lymph node flaps from within the abdominal
      cavity. This article reviews the lymph node flap options and techniques available
      for VLNT for lymphedema.

PMID- 29636652
TI  - Combining Autologous Breast Reconstruction and Vascularized Lymph Node Transfer.
AB  - Breast cancer patients are at risk for developing postmastectomy lymphedema
      syndrome of the ipsilateral upper extremity following treatment for breast cancer
      in the setting of an axillary dissection, postoperative radiation, and
      chemotherapy. For patients suffering from lymphedema who are also seeking breast
      reconstruction, combining an autologous abdominal free flap with a vascularized
      inguinal lymph node transfer provides patients the opportunity to have an
      aesthetic breast reconstruction as well as the potential to improve their
      lymphedema in a single operation. The present article aims to provide a
      description of the salient features of this approach including the preoperative
      preparation, the surgical technique, the postoperative management and
      complications, and a summary of the outcomes.

PMID- 29636653
TI  - Liposuction Treatment of Lymphedema.
AB  - In the Western world, lymphedema most commonly occurs following treatment of
      cancer. Limb reductions have been reported utilizing various conservative
      therapies including manual lymph and pressure therapy, as well as by
      microsurgical reconstruction involving lymphovenous shunts and transplantation of
      lymph vessels or nodes. Failure of these conservative and surgical treatments to
      provide complete reduction in patients with long-standing pronounced lymphedema
      is due to the persistence of excess newly formed subcutaneous adipose tissue in
      response to slow or absent lymph flow, which is not removed in patients with
      chronic non-pitting lymphedema. Traditional surgical regimes utilizing bridging
      procedures, total excision with skin grafting, or reduction plasty seldom
      achieved acceptable cosmetic and functional results. Liposuction removes the
      hypertrophied adipose tissue and is a prerequisite to achieve complete reduction,
      and this reduction is maintained long-term through constant (24 h) use of
      compression garments postoperatively. This article describes the techniques and
      evidence basis for the use of liposuction for treatment of lymphedema.

PMID- 29636655
TI  - Genetic structure, divergence and admixture of Han Chinese, Japanese and Korean
      populations.
AB  - Background: Han Chinese, Japanese and Korean, the three major ethnic groups of
      East Asia, share many similarities in appearance, language and culture etc., but
      their genetic relationships, divergence times and subsequent genetic exchanges
      have not been well studied. Results: We conducted a genome-wide study and
      evaluated the population structure of 182 Han Chinese, 90 Japanese and 100 Korean
      individuals, together with the data of 630 individuals representing 8 populations
      wordwide. Our analyses revealed that Han Chinese, Japanese and Korean populations
      have distinct genetic makeup and can be well distinguished based on either the
      genome wide data or a panel of ancestry informative markers (AIMs). Their genetic
      structure corresponds well to their geographical distributions, indicating
      geographical isolation played a critical role in driving population
      differentiation in East Asia. The most recent common ancestor of the three
      populations was dated back to 3000 ~ 3600 years ago. Our analyses also revealed
      substantial admixture within the three populations which occurred subsequent to
      initial splits, and distinct gene introgression from surrounding populations, of
      which northern ancestral component is dominant. Conclusions: These estimations
      and findings facilitate to understanding population history and mechanism of
      human genetic diversity in East Asia, and have implications for both evolutionary
      and medical studies.

PMID- 29636656
TI  - Investigating Term Reuse and Overlap in Biomedical Ontologies.
AB  - We investigate the current extent of term reuse and overlap among biomedical
      ontologies. We use the corpus of biomedical ontologies stored in the BioPortal
      repository, and analyze three types of reuse constructs: (a) explicit term reuse,
      (b) xref reuse, and (c) Concept Unique Identifier (CUI) reuse. While there is a
      term label similarity of approximately 14.4% of the total terms, we observed that
      most ontologies reuse considerably fewer than 5% of their terms from a concise
      set of a few core ontologies. We developed an interactive visualization to
      explore reuse dependencies among biomedical ontologies. Moreover, we identified a
      set of patterns that indicate ontology developers did intend to reuse terms from
      other ontologies, but they were using different and sometimes incorrect
      representations. Our results suggest the value of semi-automated tools that
      augment term reuse in the ontology engineering process through personalized
      recommendations.

PMID- 29636654
TI  - New and Emerging Treatments for Lymphedema.
AB  - Although nonoperative and operative treatments for lymphedema (LE) are well
      established, these procedures typically provide only partial relief from limb
      swelling, functional impairment, and the risk of cellulitis. The lack of a cure
      for LE, however, is due to an incomplete understanding of the underlying
      pathophysiological mechanisms, and current research efforts are focusing on
      elucidating these processes to provide new, targeted therapies for this prevalent
      disease for which there is no cure. This article reviews the current literature
      regarding the pathophysiological mechanisms that underlie LE, as well as new and
      emerging therapies for the condition.

PMID- 29636657
TI  - A Brain for Speech. Evolutionary Continuity in Primate and Human Auditory-Vocal
      Processing.
AB  - In this review article, I propose a continuous evolution from the auditory-vocal
      apparatus and its mechanisms of neural control in non-human primates, to the
      peripheral organs and the neural control of human speech. Although there is an
      overall conservatism both in peripheral systems and in central neural circuits, a
      few changes were critical for the expansion of vocal plasticity and the
      elaboration of proto-speech in early humans. Two of the most relevant changes
      were the acquisition of direct cortical control of the vocal fold musculature and
      the consolidation of an auditory-vocal articulatory circuit, encompassing
      auditory areas in the temporoparietal junction and prefrontal and motor areas in
      the frontal cortex. This articulatory loop, also referred to as the phonological
      loop, enhanced vocal working memory capacity, enabling early humans to learn
      increasingly complex utterances. The auditory-vocal circuit became progressively
      coupled to multimodal systems conveying information about objects and events,
      which gradually led to the acquisition of modern speech. Gestural communication
      accompanies the development of vocal communication since very early in human
      evolution, and although both systems co-evolved tightly in the beginning, at some
      point speech became the main channel of communication.

PMID- 29636658
TI  - Brain Electrodynamic and Hemodynamic Signatures Against Fatigue During Driving.
AB  - Fatigue is likely to be gradually cumulated in a prolonged and attention
      demanding task that may adversely affect task performance. To address the brain
      dynamics during a driving task, this study recruited 16 subjects to participate
      in an event-related lane-departure driving experiment. Each subject was
      instructed to maintain attention and task performance throughout an hour-long
      driving experiment. The subjects' brain electrodynamics and hemodynamics were
      simultaneously recorded via 32-channel electroencephalography (EEG) and 8
      source/16-detector functional near-infrared spectroscopy (fNIRS). The behavior
      performance demonstrated that all subjects were able to promptly respond to lane
      deviation events, even if the sign of fatigue arose in the brain, which suggests
      that the subjects were fighting fatigue during the driving experiment. The EEG
      event-related analysis showed strengthening alpha suppression in the occipital
      cortex, a common brain region of fatigue. Furthermore, we noted increasing
      oxygenated hemoglobin (HbO) of the brain to fight driving fatigue in the frontal
      cortex, primary motor cortex, parieto-occipital cortex and supplementary motor
      area. In conclusion, the increasing neural activity and cortical activations were
      aimed at maintaining driving performance when fatigue emerged. The electrodynamic
      and hemodynamic signatures of fatigue fighting contribute to our understanding of
      the brain dynamics of driving fatigue and address driving safety issues through
      the maintenance of attention and behavioral performance.

PMID- 29636660
TI  - Multi-Tasking and Choice of Training Data Influencing Parietal ERP Expression and
      Single-Trial Detection-Relevance for Neuroscience and Clinical Applications.
AB  - Event-related potentials (ERPs) are often used in brain-computer interfaces
      (BCIs) for communication or system control for enhancing or regaining control for
      motor-disabled persons. Especially results from single-trial EEG classification
      approaches for BCIs support correlations between single-trial ERP detection
      performance and ERP expression. Hence, BCIs can be considered as a paradigm shift
      contributing to new methods with strong influence on both neuroscience and
      clinical applications. Here, we investigate the relevance of the choice of
      training data and classifier transfer for the interpretability of results from
      single-trial ERP detection. In our experiments, subjects performed a visual-motor
      oddball task with motor-task relevant infrequent (targets), motor-task irrelevant
      infrequent (deviants), and motor-task irrelevant frequent (standards) stimuli.
      Under dual-task condition, a secondary senso-motor task was performed, compared
      to the simple-task condition. For evaluation, average ERP analysis and single
      trial detection analysis with different numbers of electrodes were performed.
      Further, classifier transfer was investigated between simple and dual task.
      Parietal positive ERPs evoked by target stimuli (but not by deviants) were
      expressed stronger under dual-task condition, which is discussed as an increase
      of task emphasis and brain processes involved in task coordination and change of
      task set. Highest classification performance was found for targets irrespective
      whether all 62, 6 or 2 parietal electrodes were used. Further, higher detection
      performance of targets compared to standards was achieved under dual-task
      compared to simple-task condition in case of training on data from 2 parietal
      electrodes corresponding to results of ERP average analysis. Classifier transfer
      between tasks improves classification performance in case that training took
      place on more varying examples (from dual task). In summary, we showed that P300
      and overlaying parietal positive ERPs can successfully be detected while subjects
      are performing additional ongoing motor activity. This supports single-trial
      detection of ERPs evoked by target events to, e.g., infer a patient's attentional
      state during therapeutic intervention.

PMID- 29636659
TI  - Solving the Credit Assignment Problem With the Prefrontal Cortex.
AB  - In naturalistic multi-cue and multi-step learning tasks, where outcomes of
      behavior are delayed in time, discovering which choices are responsible for
      rewards can present a challenge, known as the credit assignment problem. In this
      review, I summarize recent work that highlighted a critical role for the
      prefrontal cortex (PFC) in assigning credit where it is due in tasks where only a
      few of the multitude of cues or choices are relevant to the final outcome of
      behavior. Collectively, these investigations have provided compelling support for
      specialized roles of the orbitofrontal (OFC), anterior cingulate (ACC), and
      dorsolateral prefrontal (dlPFC) cortices in contingent learning. However, recent
      work has similarly revealed shared contributions and emphasized rich and
      heterogeneous response properties of neurons in these brain regions. Such
      functional overlap is not surprising given the complexity of reciprocal
      projections spanning the PFC. In the concluding section, I overview the evidence
      suggesting that the OFC, ACC and dlPFC communicate extensively, sharing the
      information about presented options, executed decisions and received rewards,
      which enables them to assign credit for outcomes to choices on which they are
      contingent. This account suggests that lesion or inactivation/inhibition
      experiments targeting a localized PFC subregion will be insufficient to gain a
      fine-grained understanding of credit assignment during learning and instead poses
      refined questions for future research, shifting the focus from focal
      manipulations to experimental techniques targeting cortico-cortical projections.

PMID- 29636661
TI  - Sumoylation Protects Against beta-Synuclein Toxicity in Yeast.
AB  - Aggregation of alpha-synuclein (alphaSyn) plays a central role in the
      pathogenesis of Parkinson's disease (PD). The budding yeast Saccharomyces
      cerevisiae serves as reference cell to study the interplay between alphaSyn
      misfolding, cytotoxicity and post-translational modifications (PTMs). The
      synuclein family includes alpha, beta and gamma isoforms. beta-synuclein
      (betaSyn) and alphaSyn are found at presynaptic terminals and both proteins are
      presumably involved in disease pathogenesis. Similar to alphaSyn, expression of
      betaSyn leads to growth deficiency and formation of intracellular aggregates in
      yeast. Co-expression of alphaSyn and betaSyn exacerbates the cytotoxicity. This
      suggests an important role of betaSyn homeostasis in PD pathology. We show here
      that the small ubiquitin-like modifier SUMO is an important determinant of
      protein stability and betaSyn-induced toxicity in eukaryotic cells.
      Downregulation of sumoylation in a yeast strain, defective for the SUMO-encoding
      gene resulted in reduced yeast growth, whereas upregulation of sumoylation
      rescued growth of yeast cell expressing betaSyn. This corroborates a protective
      role of the cellular sumoylation machinery against betaSyn-induced toxicity.
      Upregulation of sumoylation significantly reduced betaSyn aggregate formation.
      This is an indirect molecular process, which is not directly linked to betaSyn
      sumoylation because amino acid substitutions in the lysine residues required for
      betaSyn sumoylation decreased aggregation without changing yeast cellular
      toxicity. alphaSyn aggregates are more predominantly degraded by the
      autophagy/vacuole than by the 26S ubiquitin proteasome system. We demonstrate a
      vice versa situation for betaSyn, which is mainly degraded in the 26S proteasome.
      Downregulation of sumoylation significantly compromised the clearance of betaSyn
      by the 26S proteasome and increased protein stability. This effect is specific,
      because depletion of functional SUMO did neither affect betaSyn aggregate
      formation nor its degradation by the autophagy/vacuolar pathway. Our data support
      that cellular betaSyn toxicity and aggregation do not correlate in their cellular
      impact as for alphaSyn but rather represent two distinct independent molecular
      functions and molecular mechanisms. These insights into the relationship between
      betaSyn-induced toxicity, aggregate formation and degradation demonstrate a
      significant distinction between the impact of alphaSyn compared to betaSyn on
      eukaryotic cells.

PMID- 29636663
TI  - Editorial: Cellular Mechanisms of Ototoxicity.

PMID- 29636662
TI  - TRPV4 Blockade Preserves the Blood-Brain Barrier by Inhibiting Stress Fiber
      Formation in a Rat Model of Intracerebral Hemorrhage.
AB  - Blood-brain barrier (BBB) disruption and subsequent brain edema play important
      roles in the secondary neuronal death and neurological dysfunction that are
      observed following intracerebral hemorrhage (ICH). In previous studies, transient
      receptor potential vanilloid 4 (TRPV4), a calcium-permeable mechanosensitive
      channel, was shown to induce cytotoxicity in many types of cells and to play a
      role in orchestrating barrier functions. In the present study, we explored the
      role of TRPV4 in ICH-induced brain injury, specifically investigating its effect
      on BBB disruption. Autologous arterial blood was injected into the basal ganglia
      of rats to mimic ICH. Adult male Sprague Dawley rats were randomly assigned to
      sham and experimental groups for studies on the time course of TRPV4 expression
      after ICH. The selective TRPV4 antagonist HC-067047 and TRPV4 siRNA were
      administered to evaluate the effects of TRPV4 inhibition. GSK1016790A, a TRPV4
      agonist, was administered to naive rats to verify the involvement of TRPV4
      induced BBB disruption. A PKC inhibitor, dihydrochloride (H7), and a selective
      RhoA inhibitor, C3 transferase, were administered to clarify the involvement of
      the PKCalpha/RhoA/MLC2 pathway following ICH. Post-ICH assessments including
      functional tests, brain edema measurements, Evans blue extravasation, western
      blotting and immunohistochemical assays were performed. TRPV4 inhibition
      remarkably ameliorated neurological symptoms, brain edema, and neuronal death, as
      well as BBB disruption, 24-72 h following ICH. Meanwhile, TRPV4 blockade
      preserved the expression of adherens and tight junction proteins, as well as BBB
      integrity, by inhibiting stress fiber formation, which might be correlated with
      the regulation of components of the PKCalpha/RhoA/MLC2 pathway. Furthermore,
      adherens and tight junction protein degradation induced by GSK1016790A treatment
      in naive rats was also related to PKCalpha/RhoA/MLC2-pathway-mediated stress
      fiber formation. Based on these findings, therapeutic interventions targeting
      TRPV4 may represent a novel approach to ameliorate secondary brain injury
      following ICH.

PMID- 29636664
TI  - Epigenetics and Autism Spectrum Disorder: Is There a Correlation?

PMID- 29636666
TI  - Synaptic Spinules in the Olfactory Circuit of Drosophila melanogaster.
AB  - Here we report on ultrastructural features of brain synapses in the fly
      Drosophila melanogaster and outline a perspective for the study of their
      functional significance. Images taken with the aid of focused ion beam-scanning
      electron microscopy (EM) at 20 nm intervals across olfactory glomerulus DA2
      revealed that some synaptic boutons are penetrated by protrusions emanating from
      other neurons. Similar structures in the brain of mammals are known as synaptic
      spinules. A survey with transmission EM (TEM) disclosed that these structures are
      frequent throughout the antennal lobe. Detailed neuronal tracings revealed that
      spinules are formed by all three major types of neurons innervating glomerulus
      DA2 but the olfactory sensory neurons (OSNs) receive significantly more spinules
      than other olfactory neurons. Double-membrane vesicles (DMVs) that appear to
      represent material that has pinched-off from spinules are also most abundant in
      presynaptic boutons of OSNs. Inside the host neuron, a close association was
      observed between spinules, the endoplasmic reticulum (ER) and mitochondria. We
      propose that by releasing material into the host neuron, through a process
      triggered by synaptic activity and analogous to axonal pruning, synaptic spinules
      could function as a mechanism for synapse tagging, synaptic remodeling and neural
      plasticity. Future directions of experimental work to investigate this theory are
      proposed.

PMID- 29636668
TI  - The Establishment of a CSF-Contacting Nucleus "Knockout" Model Animal.
AB  - To establish an entirely cerebrospinal fluid (CSF)-contacting nucleus-deficient
      model animal, we used cholera toxin B subunit (CB)- saporin (SAP), which is an
      analog of CB-HRP that specifically labels the CSF-contacting nucleus, to
      exclusively damage the nucleus. The effectiveness and specificity of the ablation
      were evaluated upon days 1-10 after CB-SAP microinjection into the brain
      ventricular system. The vital status, survival, and common physiological
      parameters of the model animals were also assessed during the experimental
      period. The results demonstrated that CB-SAP damaged only the CSF-contacting
      nucleus, but not other functional structures, in the brain. The complete ablation
      occurred by day 7 after CB-SAP microinjection. A model animal that had no CSF
      contacting nucleus was established after survival beyond that time point. No
      obvious effects were observed in the vital status of the model animals, and their
      survival was ensured. The common physiological parameters of model animals were
      stable. The present study provides a method to establish a CSF-contacting nucleus
      "knockout" model animal, which is similar to a gene knockout model animal for
      studying this particular nucleus in vivo.

PMID- 29636665
TI  - Regulation of Brain-Derived Neurotrophic Factor and Growth Factor Signaling
      Pathways by Tyrosine Phosphatase Shp2 in the Retina: A Brief Review.
AB  - SH2 domain-containing tyrosine phosphatase-2 (PTPN11 or Shp2) is a ubiquitously
      expressed protein that plays a key regulatory role in cell proliferation,
      differentiation and growth factor (GF) signaling. This enzyme is well expressed
      in various retinal neurons and has emerged as an important player in regulating
      survival signaling networks in the neuronal tissues. The non-receptor phosphatase
      can translocate to lipid rafts in the membrane and has been implicated to
      regulate several signaling modules including PI3K/Akt, JAK-STAT and Mitogen
      Activated Protein Kinase (MAPK) pathways in a wide range of biochemical processes
      in healthy and diseased states. This review focuses on the roles of Shp2
      phosphatase in regulating brain-derived neurotrophic factor (BDNF) neurotrophin
      signaling pathways and discusses its cross-talk with various GF and downstream
      signaling pathways in the retina.

PMID- 29636669
TI  - Expression of RPRM/rprm in the Olfactory System of Embryonic Zebrafish (Danio
      rerio).
AB  - The Reprimo (RPRM) family is composed of highly conserved single-exon genes. The
      expression pattern of this gene family has been recently described during
      zebrafish (Danio rerio) embryogenesis, and primarily locates in the nervous
      system. Its most characterized member, RPRM, which duplicated to give rise rprma
      and rprmb in the fish lineage, is known to act as a tumor-suppressor gene in
      mammalian models. Here, we describe in detail the spatiotemporal expression of
      three rprm genes (rprma, rprmb, and rprml) within distinct anatomical structures
      in the developing peripheral and central nervous system. In the zebrafish, rprma
      mRNA is expressed in the olfactory placodes (OP) and olfactory epithelium (OE),
      rprmb is observed in the tectum opticum (TeO) and trigeminal ganglion (Tg),
      whereas rprml is found primarily in the telencephalon (Tel). At protein level,
      RPRM is present in a subset of cells in the OP, and neurons in the OE, TeO,
      hindbrain and sensory peripheral structures. Most importantly, the expression of
      RPRM has been conserved between teleosts and mammals. Thus, we provide a
      reference dataset describing the expression patterns of RPRM gene products during
      zebrafish and mouse development as a first step to approach the physiological
      role of the RPRM gene family.

PMID- 29636667
TI  - Ryanodine Receptors in Autophagy: Implications for Neurodegenerative Diseases?
AB  - Intracellular Ca2+ signaling is important in the regulation of several cellular
      processes including autophagy. The endoplasmic reticulum (ER) is the main and
      largest intracellular Ca2+ store. At the ER two protein families of Ca2+ release
      channels, inositol 1,4,5-trisphosphate receptors (IP3Rs) and ryanodine receptors
      (RyRs), are expressed. Several studies have reported roles in the regulation of
      autophagy for the ubiquitously expressed IP3R. For instance, IP3R-mediated Ca2+
      release supresses basal autophagic flux by promoting mitochondrial metabolism,
      while also promoting the rapid initial increase in autophagic flux in response to
      nutrient starvation. Insights into the contribution of RyRs in autophagy have
      been lagging significantly compared to the advances made for IP3Rs. This is
      rather surprising considering that RyRs are predominantly expressed in long-lived
      cells with specialized metabolic needs, such as neurons and muscle cells, in
      which autophagy plays important roles. In this review article, recent studies
      revealing roles for RyRs in the regulation of autophagy will be discussed.
      Several RyR-interacting proteins that have been established to modulate both RyR
      function and autophagy will also be highlighted. Finally, the involvement of RyRs
      in neurodegenerative diseases will be addressed. Inhibition of RyR channels has
      not only been shown to be beneficial for treating several of these diseases but
      also regulates autophagy.

PMID- 29636670
TI  - The Endocannabinoid System, Aggression, and the Violence of Synthetic Cannabinoid
      Use, Borderline Personality Disorder, Antisocial Personality Disorder, and Other
      Psychiatric Disorders.
AB  - Endogenous and exogenous cannabinoids bind to central cannabinoid receptors to
      control a multitude of behavioral functions, including aggression. The first main
      objective of this review is to dissect components of the endocannabinoid system,
      including cannabinoid 1 and cannabinoid 2 receptors; the endogenous cannabinoids
      anandamide and 2-arachidonoylglycerol; and the indirect cannabinoid modulators
      fatty acid amide hydrolase and monoacylglycerol lipase; that have shown
      abnormalities in basic research studies investigating mechanisms of aggression.
      While most human research has concluded that the active ingredient of marijuana,
      Delta9-tetrahydrocannabinol, tends to dampen rather than provoke aggression in
      acute doses, recent evidence supports a relationship between the ingestion of
      synthetic cannabinoids and emergence of violent or aggressive behavior. Thus,
      another objective is to evaluate the emerging clinical data. This paper also
      discusses the relationship between prenatal and perinatal exposure to cannabis as
      well as use of cannabis in adolescence on aggressive outcomes. A final objective
      of the paper is to discuss endocannabinoid abnormalities in psychotic and
      affective disorders, as well as clinically aggressive populations, such as
      borderline personality disorder and antisocial personality disorder. With regard
      to the former condition, decreased anandamide metabolites have been reported in
      the cerebrospinal fluid, while some preliminary evidence suggests that fatty acid
      amide hydrolase genetic polymorphisms are linked to antisocial personality
      disorder and impulsive-antisocial psychopathic traits. To summarize, this paper
      will draw upon basic and clinical research to explain how the endocannabinoid
      system may contribute to the genesis of aggressive behavior.

PMID- 29636671
TI  - Brain Atrophy and Reorganization of Structural Network in Parkinson's Disease
      With Hemiparkinsonism.
AB  - Hemiparkinsonism duration in patients with Parkinson's disease (PD) is a key time
      window to study early pathology of PD. We aimed to comprehensively explore the
      alterations of deformation and structural network in PD patients with
      hemiparkinsonism, which could potentially disclose the early biomarker for PD.
      Thirty-one PD patients with hemiparkinsonism and 37 age- and gender- matched
      normal controls were included in the present study. First of all, we normalized
      the left hemisphere of structural images as the contralateral side to the
      affected limbs. Deformation-based morphometry (DBM) was conducted to evaluate the
      brain atrophy and/or enlargement. structural networks were constructed by
      thresholding gray matter volume correlation matrices of 116 regions and analyzed
      using graph theoretical approaches (e.g., small-worldness, global, and nodal
      measures). Significantly decreased deformation values were observed in the
      temporoparietal regions like bilateral middle temporal gyri, ipsilateral
      precuneus and contralateral Rolandic operculum extending to supramarginal and
      postcentral gyri. Lower deformation values in contralateral middle temporal gyrus
      were negatively correlated with higher motor impairment which was dominated by
      akinesia/rigidity. Moreover, nodal reorganization of structural network mainly
      located in frontal, temporal, subcortex and cerebellum was bilaterally explored
      in PD patients with hemiparkinsonism. Increased nodal properties could be
      commonly observed in frontal lobes. Disruption of subcortex including basal
      ganglia and amygdala was detected by nodal local efficiency and nodal clustering
      coefficient. Twelve hubs, mainly from paralimbic-limbic and heteromodal networks,
      were disrupted and, alternatively, 14 hubs, most of which were located in frontal
      lobes, were additionally detected in PD patients with hemiparkinsonism. In
      conclusion, during hemiparkinsonism period, mild brain atrophy in the
      temporoparietal regions and widespread reorganization of structural network,
      e.g., enhanced frontal function and disruption of basal ganglia nodes, occurred
      in both hemispheres. With our data, we can also argue that MTG contralateral to
      the affected limbs (expressing clinically verified brain atrophy) might be a
      potential living biomarker to monitor disease progression. Therefore, the
      combination of DBM and structural network analyses can provide a comprehensive
      and sensitive evaluation for potential pathogenesis of early PD patients with
      hemiparkinsonism.

PMID- 29636672
TI  - Assessing Anosognosia in Apraxia of Common Tool-Use With the VATA-NAT.
AB  - In neurological patients, a lack of insight into their impairments can lead to
      possibly dangerous situations and non-compliance in rehabilitation therapy with
      worse rehabilitation outcomes as a result. This so called anosognosia is a
      multifaceted syndrome that can occur after brain damage affecting different
      neurological or cognitive functions. To our knowledge no study has investigated
      anosognosia for apraxia of common tool-use (CTU) so far. CTU-apraxia is a
      disorder frequently occurring after stroke that affects the use of familiar
      objects. Here, we introduce a new questionnaire to diagnose anosognosia for CTU
      apraxia, the Visual Analogue Test assessing Anosognosia for Naturalistic Action
      Tasks (VATA-NAT). This assessment is adapted from a series of VATA-questionnaires
      that evaluate insight into motor (VATA-M) or language (VATA-L) impairment and
      take known challenges such as aphasia into account. Fifty one subacute stroke
      patients with left (LBD) or right (RBD) brain damage were investigated including
      patients with and without CTU-apraxia. Patients were assessed with the VATA-L, -M
      and -NAT before and after applying a diagnostics session for each function.
      Interrater reliability, composite reliability as well as convergent and divergent
      validity were evaluated for the VATA-NAT. Seven percent of the LBD patients with
      CTU-apraxia demonstrated anosognosia. After tool-use diagnostics this number
      increased to 20 percent. For the VATA-NAT, psychometric data revealed high
      interrater-reliability (tau >= 0.828), composite reliability (CR >= 0.809) and
      convergent validity (tau = -0.626). When assessing patients with severe aphasia,
      the possible influence of language comprehension difficulties needs to be taken
      into account for interpretation. Overall, close monitoring of anosognosia over
      the course of rehabilitation is recommended. With the VATA-NAT we hereby provide
      a novel assessment for anosognosia in patients with CTU-apraxia. For diagnosing
      anosognosia we recommend to combine this new tool with the existing VATA-M and -L
      subtests, particularly in patients who demonstrate severe functional deficits.

PMID- 29636673
TI  - Analysis of Multichannel EEG Patterns During Human Sleep: A Novel Approach.
AB  - Classic visual sleep stage scoring is based on electroencephalogram (EEG)
      frequency band analysis of 30 s epochs and is commonly performed by highly
      trained medical sleep specialists using additional information from submental EMG
      and eye movements electrooculogram (EOG). In this study, we provide the proof-of
      principle in 40 subjects that sleep stages can be consistently differentiated
      solely on the basis of spatial 3-channel EEG patterns based on root-mean-square
      (RMS) amplitudes. The polysomnographic 3-channel EEG data are pre-processed by
      RMS averaging over intervals of 30 s leading to spatial cortical activity
      patterns represented by 3-dimensional vectors. These patterns are visualized
      using multidimensional scaling (MDS), allowing a comparison of the spatial
      cortical activity patterns with the conventional visual sleep scoring system
      according to the American Academy of Sleep Medicine (AASM). Spatial cortical
      activity patterns based on RMS amplitudes naturally divide into different
      clusters that correspond to visually scored sleep stages. Furthermore, these
      clusters are reproducible between different subjects. Especially the cluster
      associated with the REM sleep stage seems to be very different from the one
      associated with the wake state. This study provides a proof-of-principle that it
      is possible to separate sleep stages solely by analyzing spatially distributed
      EEG RMS amplitudes reflecting cortical activity and without classical EEG feature
      extractions like power spectrum analysis.

PMID- 29636675
TI  - Dynamic Information Encoding With Dynamic Synapses in Neural Adaptation.
AB  - Adaptation refers to the general phenomenon that the neural system dynamically
      adjusts its response property according to the statistics of external inputs. In
      response to an invariant stimulation, neuronal firing rates first increase
      dramatically and then decrease gradually to a low level close to the background
      activity. This prompts a question: during the adaptation, how does the neural
      system encode the repeated stimulation with attenuated firing rates? It has been
      suggested that the neural system may employ a dynamical encoding strategy during
      the adaptation, the information of stimulus is mainly encoded by the strong
      independent spiking of neurons at the early stage of the adaptation; while the
      weak but synchronized activity of neurons encodes the stimulus information at the
      later stage of the adaptation. The previous study demonstrated that short-term
      facilitation (STF) of electrical synapses, which increases the synchronization
      between neurons, can provide a mechanism to realize dynamical encoding. In the
      present study, we further explore whether short-term plasticity (STP) of chemical
      synapses, an interaction form more common than electrical synapse in the cortex,
      can support dynamical encoding. We build a large-size network with chemical
      synapses between neurons. Notably, facilitation of chemical synapses only
      enhances pair-wise correlations between neurons mildly, but its effect on
      increasing synchronization of the network can be significant, and hence it can
      serve as a mechanism to convey the stimulus information. To read-out the stimulus
      information, we consider that a downstream neuron receives balanced excitatory
      and inhibitory inputs from the network, so that the downstream neuron only
      responds to synchronized firings of the network. Therefore, the response of the
      downstream neuron indicates the presence of the repeated stimulation. Overall,
      our study demonstrates that STP of chemical synapse can serve as a mechanism to
      realize dynamical neural encoding. We believe that our study shed lights on the
      mechanism underlying the efficient neural information processing via adaptation.

PMID- 29636674
TI  - The Importance of Spatial Visual Scene Parameters in Predicting Optimal Cone
      Sensitivities in Routinely Trichromatic Frugivorous Old-World Primates.
AB  - Computational models that predict the spectral sensitivities of primate cone
      photoreceptors have focussed only on the spectral, not spatial, dimensions. On
      the ecologically valid task of foraging for fruit, such models predict the M-cone
      ("green") peak spectral sensitivity 10-20 nm further from the L-cone ("red")
      sensitivity peak than it is in nature and assume their separation is limited by
      other visual constraints, such as the requirement of high-acuity spatial vision
      for closer M and L peak sensitivities. We explore the possibility that a spatio
      chromatic analysis can better predict cone spectral tuning without appealing to
      other visual constraints. We build a computational model of the primate retina
      and simulate chromatic gratings of varying spatial frequencies using measured
      spectra. We then implement the case study of foveal processing in routinely
      trichromatic primates for the task of discriminating fruit and leaf spectra. We
      perform an exhaustive search for the configurations of M and L cone spectral
      sensitivities that optimally distinguish the colour patterns within these
      spectral images. Under such conditions, the model suggests that: (1) a long
      wavelength limit is required to constrain the L cone spectral sensitivity to its
      natural position; (2) the optimal M cone peak spectral sensitivity occurs at ~525
      nm, close to the observed position in nature (~535 nm); (3) spatial frequency has
      a small effect upon the spectral tuning of the cones; (4) a selective pressure
      toward less correlated M and L spectral sensitivities is provided by the need to
      reduce noise caused by the luminance variation that occurs in natural scenes.

PMID- 29636676
TI  - Effect of Fear of Falling on Turning Performance in Parkinson's Disease in the
      Lab and at Home.
AB  - Background: Parkinson's disease (PD) is a neurodegenerative movement disorder
      associated with gait and balance problems and a substantially increased risk of
      falling. Falls occur often during complex movements, such as turns. Both fear of
      falling (FOF) and previous falls are relevant risk factors for future falls.
      Based on recent studies indicating that lab-based and home assessment of similar
      movements show different results, we hypothesized that FOF and a positive fall
      history would influence the quantitative turning parameters differently in the
      laboratory and home. Methods: Fifty-five PD patients (43 underwent a standardized
      lab assessment; 40 were assessed over a mean of 12 days at home with
      approximately 10,000 turns per participant; and 28 contributed to both
      assessments) were classified regarding FOF and previous falls as "vigorous" (no
      FOF, negative fall history), "anxious" (FOF, negative fall history), "stoic" (no
      FOF, positive fall history) and "aware" (FOF, positive fall history). During the
      assessments, each participant wore a sensor on the lower back. Results: In the
      lab assessment, FOF was associated with a longer turning duration and lowered
      maximum and middle angular velocities of turns. In the home evaluations, a lack
      of FOF was associated with lowered maximum and average angular velocities of
      turns. Positive falls history was not significantly associated with turning
      parameters, neither in the lab nor in the home. Conclusion: FOF but not a
      positive fall history influences turning metrics in PD patients in both
      supervised and unsupervised environments, and this association is different
      between lab and home assessments. Our findings underline the relevance of
      comprehensive assessments including home-based data collection strategies for
      fall risk evaluation.

PMID- 29636677
TI  - Methyl Salicylate Lactoside Protects Neurons Ameliorating Cognitive Disorder
      Through Inhibiting Amyloid Beta-Induced Neuroinflammatory Response in Alzheimer's
      Disease.
AB  - Neuroinflammatory reactions mediated by microglia and astrocytes have been shown
      to play a key role in early progression of Alzheimer's disease (AD). Increased
      evidences have demonstrated that neurons exacerbate local inflammatory reactions
      by producing inflammatory mediators and act as an important participant in the
      pathogenesis of AD. Methyl salicylate lactoside (MSL) is an isolated natural
      product that is part of a class of novel non-steroidal anti-inflammatory drugs
      (NSAID). In our previous studies, we demonstrated that MSL exhibited therapeutic
      effects on arthritis-induced mice and suppressed the activation of glial cells.
      In the current study, we investigated the effects of MSL on cognitive function
      and neuronal protection induced by amyloid-beta peptides (Abeta) and explored
      potential underlying mechanisms involved. Amyloid precursor protein (APP) and
      presenilin 1 (PS1) double transgenic mice were used to evaluate the effects of
      MSL through behavioral testing and neuronal degenerative changes. In addition,
      copper-injured APP Swedish mutation overexpressing SH-SY5Y cells were used to
      determine the transduction of cyclooxygenase (COX) and mitogen-activated protein
      kinase (MAPK) pathways. Our results indicated that at an early stage, MSL
      treatment ameliorated cognitive impairment and neurodegeneration in APP/PS1 mice.
      Moreover, in an in vitro AD model, MSL treatment protected injured cells by
      increasing cell viability, improving mitochondrial dysfunction, and decreasing
      oxidative damage. In addition, MSL inhibited the phosphorylated level of c-Jun N
      terminal kinase (JNK) and p38 MAPK, and suppressed the expression of COX-1/2. As
      a novel NSAIDs and used for the treatment in early stage of AD, MSL clearly
      demonstrated cognitive preservation by protecting neurons via a pleiotropic anti
      inflammatory effect in the context of AD-associated deficits. Therefore, early
      treatment of anti-inflammatory therapy may be an effective strategy for treating
      AD.

PMID- 29636678
TI  - Reduction of Proliferating Olfactory Cells and Low Expression of Extracellular
      Matrix Genes Are Hallmarks of the Aged Olfactory Mucosa.
AB  - Background: The incidence of olfactory impairment increases with age; however,
      the detailed molecular and cellular mechanisms underlying this increase are yet
      to be determined. Methods: We examined the influence of aging on olfactory
      receptor neurons (ORNs), which are maintained by a unique stem cell system, from
      olfactory progenitor cells to mature ORNs, by histological comparisons of the
      physiological status of the olfactory epithelium between young adult and aged
      mice. Furthermore, we clarified the expression of genes encoding inflammatory
      cytokines, neurotrophins, growth factors, and extracellular matrix proteins to
      reveal the molecular mechanisms underlying olfactory impairment caused by aging.
      Results: The numbers of mature and immature ORNs, but not olfactory progenitors,
      decreased in the aged olfactory epithelium, with a concurrent reduction in Ki-67
      positive proliferating cells. Transcriptome analyses revealed an increase in Il6,
      encoding a component of senescence-associated secretary phenotypes (SASP), and a
      decrease in Igf1, encoding a growth factor for ORNs, in the aged nasal mucosa.
      Interestingly, expression levels of several extracellular matrix genes, including
      Col1a2, decreased in the aged nasal mucosa. Consistent with the transcriptional
      changes, the number of Col1a2-GFP-positive cells decreased in the aged lamina
      propria. Conclusions: Our data suggest that reduction in ORN number and cell
      proliferation, reduced extracellular matrix gene expression, and increased SASP
      contribute to olfactory impairment during aging.

PMID- 29636680
TI  - Cepharanthine Prevents Estrogen Deficiency-Induced Bone Loss by Inhibiting Bone
      Resorption.
AB  - Osteoporosis is a common health problem worldwide caused by an imbalance of bone
      formation vs. bone resorption. However, current therapeutic approaches aimed at
      enhancing bone formation or suppressing bone resorption still have some
      limitations. In this study, we demonstrated for the first time that cepharanthine
      (CEP, derived from Stephania cepharantha Hayata) exerted a protective effect on
      estrogen deficiency-induced bone loss. This protective effect was confirmed to be
      achieved through inhibition of bone resorption in vivo, rather than through
      enhancement of bone formation in vivo. Furthermore, the in vitro study revealed
      that CEP attenuated receptor activator of nuclear factor kappaB ligand (RANKL)
      induced osteoclast formation, and suppressed bone resorption by impairing the c
      Jun N-terminal kinase (JNK) and phosphatidylinositol 3-kinase (PI3K)-AKT
      signaling pathways. The inhibitory effect of CEP could be partly reversed by
      treatment with anisomycin (a JNK and p38 agonist) and/or SC79 (an AKT agonist) in
      vitro. Our results thus indicated that CEP could prevent estrogen deficiency
      induced bone loss by inhibiting osteoclastogenesis. Hence, CEP might be a novel
      therapeutic agent for anti-osteoporosis therapy.

PMID- 29636679
TI  - Gray/White Matter Contrast in Parkinson's Disease.
AB  - Gray/white matter contrast (GWC) decreases with aging and has been found to be a
      useful MRI biomarker in Alzheimer's disease (AD), but its utility in Parkinson's
      disease (PD) patients has not been investigated. The aims of the study were to
      test whether GWC is sensitive to aging changes in PD patients, if PD patients
      differ from healthy controls (HCs) in GWC, and whether the use of GWC data would
      improve the sensitivity of cortical thickness analyses to differentiate PD
      patients from controls. Using T1-weighted structural images, we obtained
      individual cortical thickness and GWC values from a sample of 90 PD patients and
      27 controls. Images were processed with the automated FreeSurfer stream. GWC was
      computed by dividing the white matter (WM) by the gray matter (GM) values and
      projecting the ratios onto a common surface. The sample characteristics were: 52
      patients and 14 controls were males; mean age of 64.4 +/- 10.6 years in PD and
      64.7 +/- 8.6 years in controls; 8.0 +/- 5.6 years of disease evolution; 15.6 +/-
      9.8 UPDRS; and a range of 1.5-3 in Hoehn and Yahr (H&Y) stage. In both PD and
      controls we observed significant correlations between GWC and age involving
      almost the entire cortex. When applying a stringent cluster-forming threshold of
      p < 0.0001, the correlation between GWC and age also involved the entire cortex
      in the PD group; in the control group, the correlation was found in the
      parahippocampal gyrus and widespread frontal and parietal areas. The GWC of PD
      patients did not differ from controls', whereas cortical thickness analyses
      showed thinning in temporal and parietal cortices in the PD group. Cortical
      thinning remained unchanged after adjusting for GWC. GWC is a very sensitive
      measure for detecting aging effects, but did not provide additional information
      over other parameters of atrophy in PD.

PMID- 29636681
TI  - Mechanisms of BK Channel Activation by Docosahexaenoic Acid in Rat Coronary
      Arterial Smooth Muscle Cells.
AB  - Aim: Docosahexaenoic acid (DHA) is known to activate the vascular large
      conductance calcium-activated potassium (BK) channels and has protective effects
      on the cardiovascular system. However, the underlying mechanisms through which
      DHA activates BK channels remain unclear. In this study, we determined such
      mechanisms by examining the effects of different concentrations of DHA on BK
      channels in freshly isolated rat coronary arterial smooth muscle cells (CASMCs)
      using patch clamp techniques. Methods and Results: We found that BK channels are
      the major potassium currents activated by DHA in rat CASMCs and the effects of
      DHA on BK channels are concentration dependent with a bimodal distribution. At
      concentrations of <1 MUM, DHA activated whole-cell BK currents with an EC50 of
      0.24 +/- 0.05 MUM and the activation effects were abolished by pre-incubation
      with SKF525A (10 MUM), a cytochrome P450 (CYP) epoxygenase inhibitor, suggesting
      the role of DHA-epoxide. High concentrations of DHA (1-10 MUM) activated whole
      cell BK currents with an EC50 of 2.38 +/- 0.22 MUM and the activation effects
      were unaltered by pre-incubation with SKF525A. Single channel studies showed that
      the open probabilities of BK channels were unchanged in the presence of low
      concentrations of DHA, while significantly increased with high concentrations of
      DHA. In addition, DHA induced a dose-dependent increase in cytosolic calcium
      concentrations with an EC50 of 0.037 +/- 0.01 MUM via phospholipase C (PLC)
      inositol triphosphate (IP3)-Ca2+ signal pathway, and inhibition of this pathway
      reduced DHA-induced BK activation. Conclusion: These results suggest that DHA can
      activate BK channels by multiple mechanisms. Low concentration DHA-induced BK
      channel activation is mediated through CYP epoxygenase metabolites, while high
      concentration DHA can directly activate BK channels. In addition, DHA at low and
      high concentrations can both activate BK channels by elevated cytosolic calcium
      through the PLC-IP3-Ca2+ signal pathway.

PMID- 29636682
TI  - Application of Physiologically Based Pharmacokinetic (PBPK) Modeling Within a
      Bayesian Framework to Identify Poor Metabolizers of Efavirenz (PM), Using a Test
      Dose of Efavirenz.
AB  - Poor metabolisers of CYP2B6 (PM) require a lower dose of efavirenz because of
      serious adverse reactions resulting from the higher plasma concentrations
      associated with a standard dose. Treatment discontinuation is a common
      consequence in patients experiencing these adverse reactions. Such patients
      benefit from appropriate dose reduction, where efficacy can be achieved without
      the serious adverse reactions. PMs are usually identified by genotyping. However,
      in countries with limited resources genotyping is unaffordable. Alternative cost
      effective methods of identifying a PM will be highly beneficial. This study was
      designed to determine whether a plasma concentration corresponding to a 600 mg
      test dose of efavirenz can be used to identify a PM. A physiologically based
      pharmacokinetic (PBPK) model was used to simulate the concentration-time profiles
      of a 600 mg dose of efavirenz in extensive metabolizers (EM), intermediate
      metabolizers (IM), and PM of CYP2B6. Simulated concentration-time data were used
      in a Bayesian framework to determine the probability of identifying a PM, based
      on plasma concentrations of efavirenz at a specific collection time. Results
      indicated that there was a high likelihood of differentiating a PM from other
      phenotypes by using a 24 h plasma concentration. The probability of correctly
      identifying a PM phenotype was 0.82 (true positive), while the probability of not
      identifying any other phenotype as a PM (false positive) was 0.87. A plasma
      concentration >1,000 ng/mL at 24 h post-dose is likely to be from a PM. Further
      verification of these findings using clinical studies is recommended.

PMID- 29636683
TI  - Yi Shen Juan Bi Pill Ameliorates Bone Loss and Destruction Induced by Arthritis
      Through Modulating the Balance of Cytokines Released by Different Subpopulations
      of T Cells.
AB  - The Yi Shen Juan Bi Pill (YSJB), a traditional Chinese compound herbal drug, has
      been used as an anti-rheumatic drug in clinical practice. Cartilage and bone
      destruction of inflamed joints is the hallmark of rheumatoid arthritis (RA). Our
      previous study suggested that YSJB had a protective effect on joint damage in
      collagen-induced (CIA) rats. However, the role and the mechanism of YSJB in
      inflammation-induced bone loss are unavailable. The current study aimed to
      further evaluate the effect of YSJB on the joint destruction and the systemic
      bone loss, and to clarify the potential mechanism. CIA model was generated by
      using collagen II and incomplete Freund's adjuvant in Sprague-Dawley rats. After
      4 weeks treatment, arthritic index, tissue pathology, micro-computed tomography
      scanning (MU-CT), and bone mineral density (BMD) analysis were performed. YSJB
      decreased arthritic scores and bone destruction; improved the BMD of lumbar
      vertebrae and bone volume fraction of inflamed joints. Moreover, YSJB
      significantly decreased the production of serum bone resorption markers,
      including Tartrate-Resistant Acid Phosphatase (TRACP), N-terminal telopeptide of
      type I collagen and C-terminal telopeptide of type I collagen. Meanwhile, it
      increased the level of serum bone formation marker type I collagen N-terminal
      propeptide. These results revealed that YSJB ameliorated bone destruction and
      reduced bone loss induced by arthritis. We have previously showed that Tregs
      inhibited osteoclast differentiation and bone resorption in vitro. Furthermore,
      others suggested that abnormality of Th1, Th17 may contribute to bone
      destruction. Here, we showed YSJB significantly up-regulated the percentage of
      Tregs, while also down-regulated the percentage of Th1 and Th17 cells. Our
      findings provide the evidence that YSJB ameliorates the severity of disease and
      joint degradation, and reduces systemic bone loss induced by arthritis. We
      propose YSJB modulates the balance of T cell phenotype, which affects the
      activation and differentiation of osteoclasts.

PMID- 29636684
TI  - Clozapine Use During Pregnancy and Lactation: A Case-Series Report.
AB  - The current prescription of clozapine in psychotic women of reproductive age
      makes it crucial to understand its pharmacokinetics during pregnancy and
      lactation as well as its risk profile for neonatal outcome. The aim of this case
      series was to provide new evidence on the pharmacokinetic features of clozapine
      that determine its passage through the placenta and amniotic fluid, as well as
      the neonatal clozapine elimination half-life (t1/2). This case series
      demonstrates for the first time that clozapine might show partial placental
      passage similar to other atypical antipsychotics. Clozapine levels decreased
      during the first few days in nursing infants. The half-life of clozapine in
      neonates was slightly higher than previously estimated. Clozapine use in
      pregnancy may be associated with diabetes mellitus, especially if there is a
      family history of this disease. Although no acute toxicological effects were
      observed in the intrauterine exposed newborn, close follow-up of pregnancy is
      recommended. However, these results must be taken with caution being a case
      series with small sample size.

PMID- 29636685
TI  - Nanobody-Based Biologics for Modulating Purinergic Signaling in Inflammation and
      Immunity.
AB  - Adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide (NAD+) are
      released as danger signals from cells during infection and sterile inflammation.
      In the extracellular compartment ATP is converted by CD39, CD73, and other ecto
      enzymes into metabolites that modulate the activity of T cells and macrophages.
      While ATP mediates pro-inflammatory signals via P2X7 and other P2 receptors,
      adenosine triggers anti-inflammatory signaling via the adenosine 2a receptor
      (Adora2a) and other P1 receptors. The latter also plays a role in maintaining an
      immunosuppressive tumor microenvironment. NAD+ is converted by CD38, CD203 and
      other ecto-enzymes to the Ca2+ mobilizing messengers cyclic ADP-ribose and ADP
      ribose, and to adenosine. Recent findings on the roles of CD38, CD39, CD73,
      CD203, P2X7, and Adora2a in inflammation and immunity underscore the potential of
      these proteins as drug targets. However, available small molecule inhibitors
      often lack specificity and mediate unwanted off-target toxicity. Nanobodies -
      single domain antibodies derived from heavy chain antibodies that naturally occur
      in camelids - display a propensity to bind functional epitopes not accessible to
      conventional antibodies. Like conventional antibodies, nanobodies and nanobody
      based biologics are highly specific and have well-understood, tunable in vivo
      pharmacodynamics with little if any toxicity. Nanobodies thus represent
      attractive alternatives to small molecule inhibitors for modulating purinergic
      signaling in inflammation and immunity. Here we review recent progress made in
      developing nanobodies against key targets of purinergic signaling.

PMID- 29636686
TI  - Arctigenin Inhibits Liver Cancer Tumorigenesis by Inhibiting Gankyrin Expression
      via C/EBPalpha and PPARalpha.
AB  - Burdock (Arctium lappa) is a popular vegetable in China and Japan that is
      consumed for its general health benefits. The principal active component of
      burdock is arctigenin, which shows a range of bioactivities in vivo and in vitro.
      Here, we investigated the potential anti-tumor effects of arctigenin using two
      human hepatocellular carcinoma (HCC) cell lines, HepG2 and Hep3B, and sought to
      elucidate its potential mechanisms of action. Our results showed that arctigenin
      treatment inhibited cell growth in both HepG2 and Hep3B cell lines (IC50 of 4.74
      nM for HepG2 cells, and of 59.27 nM for Hep3B cells). In addition, migration,
      invasion, and colony formation by HepG2 cells were significantly inhibited by
      arctigenin. By contrast, treatment of Hep3B cells with arctigenin did not alter
      these parameters. Arctigenin also significantly reduced the levels of gankyrin
      mRNA and protein in HepG2 cells, but not in Hep3B cells. A luciferase assay
      indicated that arctigenin targeted the -450 to -400 region of the gankyrin
      promoter. This region is also the potential binding site for both C/EBPalpha and
      PPARalpha, as predicted and confirmed by an online software analysis and ChIP
      assay. Additionally, a co-immunoprecipitation (Co-IP) assay showed that binding
      between C/EBPalpha and PPARalpha was increased in the presence of arctigenin.
      However, arctigenin did not increase the expression of C/EBPalpha or PPARalpha
      protein. A binding screening assay and liquid chromatography-mass spectrometry
      (LC-MS) were performed to identify the mechanisms by which arctigenin regulates
      gankyrin expression. The results suggested that arctigenin could directly
      increase C/EBPalpha binding to the gankyrin promoter (-432 to -422 region), but
      did not affect PPARalpha binding. Expression of gankyrin, C/EBPalpha, and
      PPARalpha were analyzed in tumor tissues of patients using real-time PCR. Both
      C/EBPalpha and PPARalpha showed negative correlations with gankyrin. In tumor
      bearing mice, arctigenin had a significant inhibitory effect on HCC growth. In
      conclusion, our results suggested that arctigenin could inhibit liver cancer
      growth by directly recruiting C/EBPalpha to the gankyrin promoter. PPARalpha
      subsequently bound to C/EBPalpha, and both had a negative regulatory effect on
      gankyrin expression. This study has identified a new mechanism of action of
      arctigenin against liver cancer growth.

PMID- 29636687
TI  - Halofuginone Attenuates Osteoarthritis by Rescuing Bone Remodeling in Subchondral
      Bone Through Oral Gavage.
AB  - Osteoarthritis (OA) is a common debilitating joint disorder worldwide without
      effective medical therapy. Articular cartilage and subchondral bone act in
      concert as a functional unit with the onset of OA. Halofuginone is an analog of
      the alkaloid febrifugine extracted from the plant Dichroa febrifuga, which has
      been demonstrated to exert inhibition of SMAD 2/3 phosphorylation downstream of
      the TGF-beta signaling pathway and osteoclastogenesis. To investigate whether
      halofuginone (HF) alleviates OA after administration by oral gavage, 3-month-old
      male mice were allocated to the Sham group, vehicle-treated anterior cruciate
      ligament transection (ACLT) group, and HF-treated ACLT group. The immunostaining
      analysis indicated that HF reduced the number of matrix metalloproteinase 13 (MMP
      13) and collagen X (Col X) positive cells in the articular cartilage. Moreover,
      HF lowered histologic OA score and prevented articular cartilage degeneration.
      The micro-computed tomography (MUCT) scan showed that HF maintained the
      subchondral bone microarchitecture, demonstrated by the restoration of bone
      volume fraction (BV/TV), subchondral bone plate thickness (SBP.Th.), and
      trabecular pattern factor (Tb.Pf) to a level comparable to that of the Sham
      group. Immunostaining for CD31 and MUCT based angiography showed that the number
      and volume of vessels in subchondral bone was restored by HF. HF administered by
      oral gavage recoupled bone remodeling and inhibited aberrant angiogenesis in the
      subchondral bone, further slowed the progression of OA. Therefore, HF
      administered by oral gavage could be a potential therapy for OA.

PMID- 29636689
TI  - D-Arg0-Bradykinin-Arg-Arg, a Latent Vasoactive Bradykinin B2 Receptor Agonist
      Metabolically Activated by Carboxypeptidases.
AB  - We previously reported hypotensive and vasodilator effects from C-terminally
      extended bradykinin (BK) sequences that behave as B2 receptor (B2R) agonists
      activated by vascular or plasma peptidases. D-Arg0-BK-Arg-Arg (r-BK-RR) is a
      novel prodrug peptide hypothetically activated by two catalytic cycles of Arg
      carboxypeptidases (CPs) to release the direct agonist D-Arg0-BK. N-terminally
      extending the BK sequence with D-Arg0 in the latter peptide was meant to block
      the second kinin inactivation pathway in importance, aminopeptidase P. The
      affinity of r-BK and r-BK-RR for recombinant B2R was assessed using a [3H]BK
      binding displacement assay. Their pharmacology was evaluated in human isolated
      umbilical vein, a contractile bioassay for the B2R, in a morphological assay
      involving the endocytosis of B2R-green fusion protein (GFP) and in anesthetized
      rats instrumented to record hemodynamic responses to bolus intravenous injection
      of both peptides. r-BK exhibited an affinity equal to that of BK for the rat B2R,
      while r-BK-RR was 61-fold less potent. In the vein and the B2R-GFP
      internalization assay, r-BK was a direct agonist unaffected by the blockade of
      angiotensin converting enzyme (ACE) with enalaprilat, or Arg-CPs with Plummer's
      inhibitor. However, the in vitro effects of r-BK-RR were reduced by these
      inhibitors, more so by enalaprilat. In anesthetized rats, r-BK and r-BK-RR were
      equipotent hypotensive agents and their effects were inhibited by icatibant (a
      B2R antagonist). The hypotensive effects of r-BK were potentiated by enalaprilat,
      but not influenced by the Arg-CPs inhibitor, which is consistent with a minor
      role of Arg-CPs in the metabolism of r-BK. However, in rats pretreated with both
      enalaprilat and Plummer's inhibitor, the hypotensive responses and the duration
      of the hypotensive episode to r-BK were significantly potentiated. The
      hypotensive responses to r-BK-RR were not affected by enalaprilat, but were
      reduced by pre-treatment with the Arg-CPs inhibitor alone or combined with
      enalaprilat. Therefore, in vivo, Arg-CPs activity is dominant over ACE to
      regenerate the B2R agonist r-BK from r-BK-RR, a prodrug activator of the B2R. A
      B2R agonist activated only at the level of the microcirculation by resident
      peptidases could be developed as an intravenously infused drug for ischemic
      diseases.

PMID- 29636688
TI  - Development of Hybrid IgG-Aptamer Sandwich Immunoassay Platform for Aflatoxin B1
      Detection and Its Evaluation Onto Various Field Samples.
AB  - The present study was aimed to develop a novel antibody-aptamer based hybrid
      detection strategy for specific and sensitive detection of aflatoxin B1 (AFB1)
      from contaminated food grains. The study comprises generation of ssDNA aptamers
      and anti-AFB1 IgG against AFB1 toxin. The generated bio-probes (aptamers and
      antibodies) were further characterized for their specificity and sensitivity
      using indirect ELISA. The generated aptamers namely AFB1a and AFB1b showed
      prominent reactivity and selectivity against AFB1 toxin. These aptamers were
      further characterized for their secondary structures and dG values were
      determined as -4.6 and -2.75 Kcal/mol, respectively. The detection limit (LOD) of
      AFB1a and anti-AFB1 IgG was determined as 5 and 10 ng/mL, respectively. The
      characterized aptamers and antibodies against AFB1 were used to develop the
      sandwich immunoassay. Anti AFB1 IgG was used as a capturing antibody whereas anti
      AFB1a aptamer was used as its revealing partner in the assay. The limit of
      detection (LOD) of the immunoassay was determined to be 5 ng/mL of AFB1 standard
      toxin and showed no cross-reactivity with closely related mycotoxins. To assess
      the reliability of the developed method, several field samples contaminated with
      aflatoxin B1 was included in the study and results were validated with commercial
      AFB1-ELISA Kit. Additionally, the spiking studies were also carried out to
      demonstrate the consistency and dependability of the developed hybrid sandwich
      immunoassay wherein the toxins recovered were found to be ranging between 73 and
      98.80% with the LOD at 5 ng/mL. In conclusion, the developed method may find the
      better utility in routine food testing laboratories for assessment of AFB1.

PMID- 29636690
TI  - AIPpred: Sequence-Based Prediction of Anti-inflammatory Peptides Using Random
      Forest.
AB  - The use of therapeutic peptides in various inflammatory diseases and autoimmune
      disorders has received considerable attention; however, the identification of
      anti-inflammatory peptides (AIPs) through wet-lab experimentation is expensive
      and often time consuming. Therefore, the development of novel computational
      methods is needed to identify potential AIP candidates prior to in vitro
      experimentation. In this study, we proposed a random forest (RF)-based method for
      predicting AIPs, called AIPpred (AIP predictor in primary amino acid sequences),
      which was trained with 354 optimal features. First, we systematically studied the
      contribution of individual composition [amino acid-, dipeptide composition (DPC),
      amino acid index, chain-transition-distribution, and physicochemical properties]
      in AIP prediction. Since the performance of the DPC-based model is significantly
      better than that of other composition-based models, we applied a feature
      selection protocol on this model and identified the optimal features. AIPpred
      achieved an area under the curve (AUC) value of 0.801 in a 5-fold cross
      validation test, which was ~2% higher than that of the control RF predictor
      trained with all DPC composition features, indicating the efficiency of the
      feature selection protocol. Furthermore, we evaluated the performance of AIPpred
      on an independent dataset, with results showing that our method outperformed an
      existing method, as well as 3 different machine learning methods developed in
      this study, with an AUC value of 0.814. These results indicated that AIPpred will
      be a useful tool for predicting AIPs and might efficiently assist the development
      of AIP therapeutics and biomedical research. AIPpred is freely accessible at
      www.thegleelab.org/AIPpred.

PMID- 29636691
TI  - TAAR1 in Addiction: Looking Beyond the Tip of the Iceberg.
AB  - Trace-amine associated receptor 1 (TAAR1) is the best-characterized member of the
      family of TAARs. TAAR1 is broadly expressed in the brain, especially within the
      monoaminergic systems. Evidence from electrophysiological and neurochemical
      studies evaluating the effects of genetic and pharmacological interventions on
      TAAR1 revealed that TAAR1 modulates transmission of monoamines, especially
      dopamine. TAAR1 agonists dampened drugs of abuse-induced dopamine accumulation.
      In general, TAAR1 agonists specifically inhibited the rewarding and reinforcing
      effects of drugs of abuse and drug-abuse related behaviors. Details of the
      mechanism of TAAR1 remain elusive; however, it is thought to be regulated by its
      interactions with D2 receptors. In addition, the alternative cellular mechanism
      such as an interaction between TAAR1 and D3 may also participate in the action of
      TAAR1 agonists. Further studies are required to investigate the role of TAAR1 in
      other drugs of abuse-related behaviors and the underlying neural mechanisms.
      Collectively, TAAR1 negatively modulates dopaminergic systems and dopamine
      related behaviors and TAAR1 agonists are promising pharmacotherapy to treat drug
      addiction and relapse.

PMID- 29636692
TI  - Managed Entry Agreements for Pharmaceuticals in the Context of Adaptive Pathways
      in Europe.
AB  - As per the EMA definition, adaptive pathways is a scientific concept for the
      development of medicines which seeks to facilitate patient access to promising
      medicines addressing high unmet need through a prospectively planned approach in
      a sustainable way. This review reports the findings of activities undertaken by
      the ADAPT-SMART consortium to identify enablers and explore the suitability of
      managed entry agreements for adaptive pathways products in Europe. We found that
      during 2006-2016 outcomes-based managed entry agreements were not commonly used
      for products with a conditional marketing authorization or authorized under
      exceptional circumstances. The barriers and enablers to develop workable managed
      entry agreements models for adaptive pathways products were discussed through
      interviews and a multi-stakeholder workshop with a number of recommendations made
      in this paper.

PMID- 29636693
TI  - Erzhi Pill(r) Protected Experimental Liver Injury Against Apoptosis via the
      PI3K/Akt/Raptor/Rictor Pathway.
AB  - Erzhi Pill (EZP) is one of the basic prescriptions for treating liver diseases in
      traditional Chinese medicine. However, its mechanism of action is still
      undefined. The PI3K/AKT/Raptor/Rictor signaling pathway is closely related to
      apoptosis and plays a significant role in the pathogenesis of liver disease. To
      define the mechanism of the hepatoprotective effect of EZP in the treatment of
      liver disease, hepatic injury induced by 2-acetylaminofluorene/partial
      hepatectomy was treated by EZP for 14 days. The therapeutic effect of EZP was
      confirmed by the decreased production of aspartate aminotransferase and alanine
      aminotransferase, recovery of pathological liver injury, followed by inhibition
      of pro-inflammatory cytokines and transforming growth factor-beta1.
      Bromodeoxyuridine assay and TUNEL staining indicated that apoptosis was
      suppressed and the numbers of cells in S phase and G0/G1phase were decreased. The
      crucial proteins in the PI3K/AKT/Raptor/Rictor signaling pathway were deactivated
      in rats with experimental liver injury treated by EZP. These results indicated
      that the hepatoprotective effect of EZP via inhibition of hepatocyte apoptosis
      was closely related to repression of the PI3K/Akt/Raptor/Rictor signaling
      pathway.

PMID- 29636694
TI  - Topical Bixin Confers NRF2-Dependent Protection Against Photodamage and Hair
      Graying in Mouse Skin.
AB  - Environmental exposure to solar ultraviolet (UV) radiation causes acute
      photodamage, premature aging, and skin cancer, attributable to UV-induced
      genotoxic, oxidative, and inflammatory stress. The transcription factor NRF2
      [nuclear factor erythroid 2 (E2)-related factor 2] is the master regulator of the
      cellular antioxidant response protecting skin against various environmental
      stressors including UV radiation and electrophilic pollutants. NRF2 in epidermal
      keratinocytes can be activated using natural chemopreventive compounds such as
      the apocarotenoid bixin, an FDA-approved food additive and cosmetic ingredient
      from the seeds of the achiote tree (Bixa orellana). Here, we tested the
      feasibility of topical use of bixin for NRF2-dependent skin photoprotection in
      two genetically modified mouse models [SKH1 and C57BL/6J (Nrf2+/+ versus Nrf2-/-
      )]. First, we observed that a bixin formulation optimized for topical NRF2
      activation suppresses acute UV-induced photodamage in Nrf2+/+ but not Nrf2-/-
      SKH1 mice, a photoprotective effect indicated by reduced epidermal
      hyperproliferation and oxidative DNA damage. Secondly, it was demonstrated that
      topical bixin suppresses PUVA (psoralen + UVA)-induced hair graying in Nrf2+/+
      but not Nrf2-/- C57BL/6J mice. Collectively, this research provides the first in
      vivo evidence that topical application of bixin can protect against UV-induced
      photodamage and PUVA-induced loss of hair pigmentation through NRF2 activation.
      Topical NRF2 activation using bixin may represent a novel strategy for human skin
      photoprotection, potentially complementing conventional sunscreen-based
      approaches.

PMID- 29636696
TI  - Athlete Performance Monitoring in Anti-Doping.

PMID- 29636695
TI  - The Selective Angiotensin II Type 2 Receptor Agonist, Compound 21, Attenuates the
      Progression of Lung Fibrosis and Pulmonary Hypertension in an Experimental Model
      of Bleomycin-Induced Lung Injury.
AB  - Idiopathic Pulmonary Fibrosis (IPF) is a chronic lung disease characterized by
      scar formation and respiratory insufficiency, which progressively leads to death.
      Pulmonary hypertension (PH) is a common complication of IPF that negatively
      impacts clinical outcomes, and has been classified as Group III PH. Despite
      scientific advances, the dismal prognosis of IPF and associated PH remains
      unchanged, necessitating the search for novel therapeutic strategies.
      Accumulating evidence suggests that stimulation of the angiotensin II type 2
      (AT2) receptor confers protection against a host of diseases. In this study, we
      investigated the therapeutic potential of Compound 21 (C21), a selective AT2
      receptor agonist in the bleomycin model of lung injury. A single intra-tracheal
      administration of bleomycin (2.5 mg/kg) to 8-week old male Sprague Dawley rats
      resulted in lung fibrosis and PH. Two experimental protocols were followed: C21
      was administered (0.03 mg/kg/day, ip) either immediately (prevention protocol,
      BCP) or after 3 days (treatment protocol, BCT) of bleomycin-instillation.
      Echocardiography, hemodynamic, and Fulton's index assessments were performed
      after 2 weeks of bleomycin-instillation. Lung tissue was processed for gene
      expression, hydroxyproline content (a marker of collagen deposition), and
      histological analysis. C21 treatment prevented as well as attenuated the
      progression of lung fibrosis, and accompanying PH. The beneficial effects of C21
      were associated with decreased infiltration of macrophages in the lungs, reduced
      lung inflammation and diminished pulmonary collagen accumulation. Further, C21
      treatment also improved pulmonary pressure, reduced muscularization of the
      pulmonary vessels and normalized cardiac function in both the experimental
      protocols. However, there were no major differences in any of the outcomes
      measured from the two experimental protocols. Collectively, our findings indicate
      that stimulation of the AT2 receptor by C21 attenuates bleomycin-induced lung
      injury and associated cardiopulmonary pathology, which needs to be further
      explored as a promising approach for the clinical treatment of IPF and Group III
      PH.

PMID- 29636697
TI  - Molecular Defects in Cardiac Myofilament Ca2+-Regulation Due to Cardiomyopathy
      Linked Mutations Can Be Reversed by Small Molecules Binding to Troponin.
AB  - The inherited cardiomyopathies, hypertrophic cardiomyopathy (HCM) and dilated
      cardiomyopathy (DCM) are relatively common, potentially life-threatening and
      currently untreatable. Mutations are often in the contractile proteins of cardiac
      muscle and cause abnormal Ca2+ regulation via troponin. HCM is usually linked to
      higher myofilament Ca2+-sensitivity whilst in both HCM and DCM mutant tissue
      there is often an uncoupling of the relationship between troponin I (TnI)
      phosphorylation by PKA and modulation of myofilament Ca2+-sensitivity, essential
      for normal responses to adrenaline. The adrenergic response is blunted, and this
      may predispose the heart to failure under stress. At present there are no
      compounds or interventions that can prevent or treat sarcomere cardiomyopathies.
      There is a need for novel therapies that act at a more fundamental level to
      affect the disease process. We demonstrated that epigallocatechin-3 gallate
      (EGCG) was found to be capable of restoring the coupled relationship between Ca2+
      sensitivity and TnI phosphorylation in mutant thin filaments to normal in vitro,
      independent of the mutation (15 mutations tested). We have labeled this property
      "re-coupling." The action of EGCG in vitro to reverse the abnormality caused by
      myopathic mutations would appear to be an ideal pharmaceutical profile for
      treatment of inherited HCM and DCM but EGCG is known to be promiscuous in vivo
      and is thus unsuitable as a therapeutic drug. We therefore investigated whether
      other structurally related compounds can re-couple myofilaments without these off
      target effects. We used the quantitative in vitro motility assay to screen 40
      compounds, related to C-terminal Hsp90 inhibitors, and found 23 that can re
      couple mutant myofilaments. There is no correlation between re-couplers and Hsp90
      inhibitors. The Ca2+-sensitivity shift due to TnI phosphorylation was restored to
      2.2 +/- 0.01-fold (n = 19) compared to 2.0 +/- 0.24-fold (n = 7) in wild-type
      thin filaments. Many of these compounds were either pure re-couplers or pure
      desensitizers, indicating these properties are independent; moreover, re-coupling
      ability could be lost with small changes of compound structure, indicating the
      possibility of specificity. Small molecules that can re-couple may have
      therapeutic potential. HIGHLIGHTS - Inherited cardiomyopathies are common
      diseases that are currently untreatable at a fundamental level and therefore
      finding a small molecule treatment is highly desirable.- We have identified a
      molecular level dysfunction common to nearly all mutations: uncoupling of the
      relationship between troponin I phosphorylation and modulation of myofilament
      Ca2+-sensitivity, essential for normal responses to adrenaline.- We have
      identified a new class of drugs that are capable of both reducing Ca2+
      sensitivity and/or recouping the relationship between troponin I phosphorylation
      and Ca2+-sensitivity.- The re-coupling phenomenon can be explained on the basis
      of a single mechanism that is testable.- Measurements with a wide range of small
      molecules of varying structures can indicate the critical molecular features
      required for recoupling and allows the prediction of other potential re-couplers.

PMID- 29636698
TI  - Leptin Signaling in the Carotid Body Regulates a Hypoxic Ventilatory Response
      Through Altering TASK Channel Expression.
AB  - Leptin is an adipose-derived hormone that plays an important role in the
      regulation of breathing. It has been demonstrated that obesity-related
      hypoventilation or apnea is closely associated with leptin signaling pathways.
      Perturbations of leptin signaling probably contribute to the reduced sensitivity
      of respiratory chemoreceptors to hypoxia/hypercapnia. However, the underlying
      mechanism remains incompletely understood. The present study is to test the
      hypothesis that leptin signaling contributes to modulating a hypoxic ventilatory
      response. The respiratory function was assessed in conscious obese Zucker rats or
      lean littermates treated with an injection of leptin. During exposure to hypoxia,
      the change in minute ventilation was lower in obese Zucker rats than chow-fed
      lean littermates or high fat diet-fed littermates. Such a change was abolished in
      all groups after carotid body denervation. In addition, the expression of
      phosphorylated signal transducers and activators of transcription 3 (pSTAT3), as
      well as putative O2-sensitive K+ channels including TASK-1, TASK-3 and TASK-2 in
      the carotid body, was significantly reduced in obese Zucker rats compared with
      the other two phenotype littermates. Chronic administration of leptin in chow-fed
      lean Zucker rats failed to alter basal ventilation but vigorously increased tidal
      volume, respiratory frequency, and therefore minute volume during exposure to
      hypoxia. Likewise, carotid body denervation abolished such an effect. In
      addition, systemic leptin elicited enhanced expression of pSTAT3 and TASK
      channels. In conclusion, these data demonstrate that leptin signaling facilitates
      hypoxic ventilatory responses probably through upregulation of pSTAT3 and TASK
      channels in the carotid body. These findings may help to better understand the
      pathogenic mechanism of obesity-related hypoventilation or apnea.

PMID- 29636699
TI  - Dendritic Cell Migration Toward CCL21 Gradient Requires Functional Cx43.
AB  - Dendritic cells (DCs) travel through lymphatic vessels to transport antigens and
      present them to T cells in lymph nodes. DCs move directionally toward lymphatics
      by virtue of their CCR7 and a CCL21 chemotactic gradient. We evaluated in vivo
      and in bone marrow-derived dendritic cells (BMDCs) whether the gap junction
      protein Cx43 contributes to CCL21/CCR7-dependent DC migration in wild-type (WT)
      mice, heterozygous (Cx43+/-) mice and mice expressing a truncated form of Cx43
      lacking its regulatory C-terminus (Cx43K258/-). In a model of flank skin
      inflammation, we found that the recruitment of myeloid DCs (mDCs) to skin
      draining lymph nodes was reduced in Cx43K258/- mice as compared to WT and Cx43+/-
      mice. In addition, the migration of Cx43K258/- BMDCs toward CCL21 was abolished
      in an in vitro chemotactic assay while it was only reduced in Cx43+/- cells. Both
      mutant genotypes showed defects in the directionality of BMDC migration as
      compared to WT BMDCs. No difference was found between the three populations of
      BMDCs in terms of expression of surface markers (CD11c, CD86, CD80, CD40, MHC-II,
      and CCR7) after differentiation and TLR activation. Finally, examination of the
      CCR7-induced signaling pathways in BMDCs revealed normal receptor-induced
      mobilization of intracellular Ca2+. These results demonstrate that full
      expression of an intact Cx43 is critical to the directionality and rate of DC
      migration, which may be amenable to regulation of the immune response.

PMID- 29636700
TI  - Phosphodiesterase-5 Inhibition Alleviates Pulmonary Hypertension and Basal Lamina
      Thickening in Rats Challenged by Chronic Hypoxia.
AB  - Background: Hypoxia represents both an outcome of cardiopulmonary diseases and a
      trigger for severe pulmonary complications as pulmonary hypertension. Because
      nitric oxide (NO) is a critical mediator in the development of pulmonary
      hypertension, the modulators of its downstream function may become target of
      pharmacological interventions aimed at alleviating the impact of this condition.
      Here, we investigate the effects of an early administration of phosphodiesterase
      5 inhibitor in rats where pulmonary artery hypertension was induced by chronic
      exposure to hypoxia. Methods: Rats were divided into three groups: normoxic
      control, hypoxic with no treatments (2 weeks breathing an atmosphere containing
      10% oxygen), and hypoxic treated with sildenafil (1.4 mg/Kg per day in 0.3 mL
      i.p.). After sacrifice, hearts and lungs were removed and harvested for analyses.
      Results: Sildenafil reduced hypoxia-induced right ventricle hypertrophy without
      effects in lung hypertrophy, and blunted the increase in right ventricle pressure
      without effects on left ventricle pressure. Furthermore, the NO-producing systems
      (i.e., the phosphorylation of the endothelial isoforms of NO synthase that was
      measured in both myocardial and lung tissues), and the blood NO stores (i.e., the
      plasma level of nitrates and nitrites) were up-regulated by sildenafil. We did
      not find significant effects of sildenafil on weight and hemoglobin
      concentration. Morphological analysis in lung biopsies revealed that 2-week
      hypoxia increased the frequency of small pulmonary vessels leaving large vessels
      unaffected. Finally, ultrastructural analysis showed that sildenafil down
      regulated the hypoxia-induced increase in the thickness of the pulmonary basal
      lamina. Conclusions: In this model of pulmonary hypertension, sildenafil
      contrasts the negative effects of hypoxia on pulmonary vascular and right
      ventricle remodeling. This action does not only encompass the canonical
      vasomodulatory effect, but involves several biochemical pathways. Although the
      human pathological model is certainly more complex than that described here (for
      example, the inflammatory issue), the potential role of phosphodiesterase-5 for
      long-term treatment, and perhaps prevention, of pulmonary hypertension is worthy
      of investigation.

PMID- 29636701
TI  - Identification, Expression Patterns, and Functional Characterization of
      Chemosensory Proteins in Dendroctonus armandi (Coleoptera: Curculionidae:
      Scolytinae).
AB  - The Chinese white pine beetle, Dendroctonus armandi Tsai and Li (Coleoptera:
      Curculionidae: Scolytinae), is a serious pest of coniferous forests in China.
      Thus, there is considerable interest in developing eco-friendly pest-control
      methods, with the use of semiochemicals as a distinct possibility. Olfaction is
      extremely important for fitness of D. armandi because it is the primary mechanism
      through which the insect locates hosts and mates. Thus, here we characterized
      nine full-length genes encoding chemosensory proteins (CSPs) from D. armandi. The
      genes were ubiquitously and multiply expressed across different developmental
      stages and adult tissues, indicating various roles in developmental
      metamorphosis, olfaction, and gustation. Ligand-binding assays implied that
      DarmCSP2 may be the carrier of D. armandi pheromones and various plant host
      volatiles. These volatiles were identified through RNA interference of DarmCSP2
      as: (+)-alpha-pinene, (+)-beta-pinene, (-)-beta-pinene, (+)-camphene, (+)-3
      carene, and myrcene. The systematic chemosensory functional analysis of DarmCSP2
      in this study clarified the molecular mechanisms underlying D. armandi olfaction
      and provided a theoretical foundation for eco-friendly pest control.

PMID- 29636703
TI  - Extravascular Hydrophobic Surfaces, Fat Droplets, and the Connection With
      Decompression Illness: Spinal, Joint Pain, and Dysbaric Osteonecrosis.

PMID- 29636704
TI  - Altered Gray Matter Volume and Resting-State Connectivity in Individuals With
      Internet Gaming Disorder: A Voxel-Based Morphometry and Resting-State Functional
      Magnetic Resonance Imaging Study.
AB  - Neuroimaging studies on the characteristics of individuals with Internet gaming
      disorder (IGD) have been accumulating due to growing concerns regarding the
      psychological and social problems associated with Internet use. However,
      relatively little is known about the brain characteristics underlying IGD, such
      as the associated functional connectivity and structure. The aim of this study
      was to investigate alterations in gray matter (GM) volume and functional
      connectivity during resting state in individuals with IGD using voxel-based
      morphometry and a resting-state connectivity analysis. The participants included
      20 individuals with IGD and 20 age- and sex-matched healthy controls. Resting
      state functional and structural images were acquired for all participants using 3
      T magnetic resonance imaging. We also measured the severity of IGD and
      impulsivity using psychological scales. The results show that IGD severity was
      positively correlated with GM volume in the left caudate (p < 0.05, corrected for
      multiple comparisons), and negatively associated with functional connectivity
      between the left caudate and the right middle frontal gyrus (p < 0.05, corrected
      for multiple comparisons). This study demonstrates that IGD is associated with
      neuroanatomical changes in the right middle frontal cortex and the left caudate.
      These are important brain regions for reward and cognitive control processes, and
      structural and functional abnormalities in these regions have been reported for
      other addictions, such as substance abuse and pathological gambling. The findings
      suggest that structural deficits and resting-state functional impairments in the
      frontostriatal network may be associated with IGD and provide new insights into
      the underlying neural mechanisms of IGD.

PMID- 29636702
TI  - Adipokine Profiling in Adult Women With Central Obesity and Hypertension.
AB  - Central obesity and hypertension are common risk factors for the metabolic
      syndrome, cardiovascular and renal diseases. Studies have shown that it is more
      difficult to control blood pressure and prevent end-organ damage in obese
      individuals with hypertension compared to their non-obese counterparts,
      especially among women. Obese females have a 6 times higher risk of developing
      hypertension than non-obese females while obese males are at a 1.5 times higher
      risk of developing hypertension, compared to their non-obese counterparts.
      Indeed, the inter-relationship between obesity and hypertension is unclear.
      Adipokines have been proposed to play a mediating role in the relationship
      between obesity and hypertension and are involved in the pathogenesis of
      metabolic diseases. Therefore, this study sought to determine the role of
      adipokines (adiponectin, plasminogen activator inhibitor-1, leptin, and tumor
      necrosis factor-alpha) in hypertensive Hong Kong Chinese women with central
      obesity. A total of 387 women aged 58 +/- 11 years who were examined with a 2 * 2
      factorial design for central obesity (waist circumference >= 80 cm) and
      hypertension (blood pressure >= 140/90 mmHg), were recruited from a pool of 1,492
      Hong Kong Chinese adults who were previously screened for metabolic syndrome.
      Subjects with hyperglycemia, hypertriglyceridemia, and dyslipidemia were excluded
      to eliminate confounding effects. Our findings revealed that hypertensive women
      with central obesity had a lower anti-inflammatory status (adiponectin) and a
      higher pro-inflammatory status (TNF-alpha) than obese alone or hypertensive alone
      women. Also, women with central obesity had higher circulatory PAI-1 and leptin
      concentrations than their non-obese counterparts. We conclude that obesity may
      shift toward a more pro-inflammatory state and may become more severe in the
      presence of hypertension or vice versa.

PMID- 29636705
TI  - Non-Dependent and Dependent Daily Cannabis Users Differ in Mental Health but Not
      Prospective Memory Ability.
AB  - Research suggests that daily cannabis users have impaired memory for past events,
      but it is not clear whether they are also impaired in prospective memory (PM) for
      future events. The present study examined PM in daily cannabis users who were
      either dependent (n = 18) or non-dependent (n = 18), and compared them with non
      using controls (n = 18). The effect of future event simulation (FES) on PM
      performance was also examined. Participants were matched across groups on age,
      gender, and highest level of education. The virtual week (VW) was used to
      objectively assess PM abilities, both at baseline and following FES. Other
      measures used were: cannabis use variables, immediate and delayed prose recall,
      phonemic and category fluency, spot-the-word test (premorbid intelligence), Beck
      Depression Inventory, Beck Anxiety Inventory, and a measure of schizotypy (Oxford
      Liverpool Inventory of Feelings and Experiences: unusual experiences subscale).
      No group differences were found in PM performance on the VW, and FES did not
      improve PM performance in any group. Dependent cannabis users scored higher on
      depression, anxiety, and schizotypy than both other groups with non-dependent
      cannabis users scoring at a similar level to controls. There were no group
      differences in alcohol use. Findings suggest that when carefully matched on
      baseline variables, and not differing in premorbid IQ or alcohol use, young, near
      daily cannabis users do not differ from non-using controls in PM performance.

PMID- 29636706
TI  - A Randomized Controlled Trial Comparing Behavioral, Educational, and
      Pharmacological Treatments in Youths With Chronic Tic Disorder or Tourette
      Syndrome.
AB  - Context: The existing literature on the treatment of pediatric chronic tic
      disorder (CTD) and Tourette syndrome (TS) indicates that both behavioral therapy
      (BT) and pharmacotherapy (PT) are effective for reducing symptoms. Objective: To
      evaluate the efficacy of BT compared to psychoeducation (PE) or PT for reducing
      tics and co-occurring symptoms and for improving quality of life (QoL) in a
      sample of youths with CTD and TS. Design: A 10 weeks, 2 sites (Catania, Rome)
      randomized controlled trial. Participants were randomized to receive one of the
      following treatments: BT, PE, or PT. Participants: 110 outpatients aged between 8
      and 17 years affected by CTD or TS. Results: Patients in the BT and PT groups
      showed a significant reduction in the severity of tic symptoms, while the PE
      group did not show any improvement. PT was more effective for reducing obsessive
      compulsive symptoms than BT, while PE group did not show any improvement. Both BT
      and PT groups showed an improvement in most QoL domains, whereas no differences
      were found in the PE group. Conclusions: BT is as effective as pharmacological
      therapy in the treatment of tic disorders in children and adolescents, thus
      offering an alternative to medications for CTD and TS.

PMID- 29636708
TI  - Antidepressant-Like Effects of Acupuncture-Insights From DNA Methylation and
      Histone Modifications of Brain-Derived Neurotrophic Factor.
AB  - Sensitive and stable biomarkers that facilitate depression detection and monitor
      the antidepressant efficiency are currently unavailable. Thus, the objective is
      to investigate the potential of DNA methylation and histone modifications of
      brain-derived neurotrophic factor (BDNF) in monitoring severity and
      antidepressive effects of acupuncture. The depression rat model was imitated by
      social isolation and chronic unpredicted mild stress (CUMS). The expression of
      serum BDNF was detected by enzyme-linked immunosorbent assay (ELISA), the
      hippocampal BDNF, acetylation levels in histone H3 lysine 9 (acH3K9), and HDAC2
      by Western blot, the hippocampal mRNA of BDNF by RT-polymerase chain reaction
      (PCR). The DNA methylation patterns of the promoter I of BDNF was detected by MS
      PCR. We investigated that the expression of BDNF in serum and hippocampus were
      significantly downregulated compared with controls. The same trend was found in
      mRNA of BDNF. Notably, acupuncture reversed the downregulation of BDNF in serum
      and hippocampus and mRNA of BDNF compared with model group. Acupuncture reversed
      the CUMS-induced downregulation of hippocampal acH3K9. On the contrary, the CUMS
      induced upregulation of hippocampal HDAC2 in model group was significantly
      reversed by acupuncture. Collectively, the antidepressant effect of acupuncture
      might be mediated by regulating the DNA methylation and histone modifications of
      BDNF, which may represent novel biomaker for detection of depression and
      monitoring severity and antidepressive effects.

PMID- 29636707
TI  - Recognizing Psychiatric Comorbidity With Reading Disorders.
AB  - Reading disorder (RD), a specific learning disorder (SLD) of reading that
      includes impairment in word reading, reading fluency, and/or reading
      comprehension, is common in the general population but often is not
      comprehensively understood or assessed in mental health settings. In education
      settings, comorbid mental and associated disorders may be inadequately integrated
      into intervention plans. Assessment and intervention for RD may be delayed or
      absent in children with frequently co-occurring mental disorders not fully
      responding to treatment in both school and mental health settings. To address
      this oversight, this review summarizes current knowledge regarding RDs and common
      comorbid or co-occurring disorders that are important for mental health and
      school settings. We chose to highlight RD because it is the most common SLD, and
      connections to other often comorbid disorders have been more thoroughly described
      in the literature. Much of the literature we describe is on decoding-based RD (or
      developmental dyslexia) as it is the most common form of RD. In addition to risk
      for academic struggle and social, emotional, and behavioral problems, those with
      RD often show early evidence of combined or intertwined Diagnostic and
      Statistical Manual of Mental Disorders, Fifth Edition childhood disorders. These
      include attention deficit hyperactivity disorder, anxiety and depression,
      disruptive, impulse-control, and conduct disorders, autism spectrum disorders,
      and other SLDs. The present review highlights issues and areas of controversy
      within these comorbidities, as well as directions for future research. An
      interdisciplinary, integrated approach between mental health professionals and
      educators can lead to comprehensive and targeted treatments encompassing both
      academic and mental health interventions. Such targeted treatments may contribute
      to improved educational and health-related outcomes in vulnerable youth. While
      there is a growing research literature on this association, more studies are
      needed of when to intervene and of the early and long-term benefits of
      comprehensive intervention.

PMID- 29636709
TI  - Religious Fundamentalism Modulates Neural Responses to Error-Related Words: The
      Role of Motivation Toward Closure.
AB  - Examining the relationship between brain activity and religious fundamentalism,
      this study explores whether fundamentalist religious beliefs increase responses
      to error-related words among participants intolerant to uncertainty (i.e., high
      in the need for closure) in comparison to those who have a high degree of
      toleration for uncertainty (i.e., those who are low in the need for closure). We
      examine a negative-going event-related brain potentials occurring 400 ms after
      stimulus onset (the N400) due to its well-understood association with the
      reactions to emotional conflict. Religious fundamentalism and tolerance of
      uncertainty were measured on self-report measures, and electroencephalographic
      neural reactivity was recorded as participants were performing an emotional
      Stroop task. In this task, participants read neutral words and words related to
      uncertainty, errors, and pondering, while being asked to name the color of the
      ink with which the word is written. The results confirm that among people who are
      intolerant of uncertainty (i.e., those high in the need for closure), religious
      fundamentalism is associated with an increased N400 on error-related words
      compared with people who tolerate uncertainty well (i.e., those low in the need
      for closure).

PMID- 29636710
TI  - Psychometric Properties of the Italian Version of the Young Schema Questionnaire
      L-3: Preliminary Results.
AB  - Schema Therapy (ST) is a well-known approach for the treatment of personality
      disorders. This therapy integrates different theories and techniques into an
      original and systematic treatment model. The Young Schema Questionnaire L-3 (YSQ
      L3) is a self-report instrument, based on the ST model, designed to assess 18
      Early Maladaptive Schemas (EMSs). During the last decade, it has been translated
      and validated in different countries and languages. This study aims to establish
      the psychometric properties of the Italian Version of the YSQ-L3. We enrolled two
      groups: a clinical (n = 148) and a non-clinical one (n = 918). We investigated
      the factor structure, reliability and convergent validity with anxiety and
      depression between clinical and non-clinical groups. The results highlighted a
      few relevant findings. Cronbach's alpha showed significant values for all the
      schemas. All of the factor models do not seem highly adequate, even if the
      hierarchical model has proven to be the most significant one. Furthermore, the
      questionnaire confirms the ability to discriminate between clinical and non
      clinical groups and could represent a useful tool in the clinical practice.
      Limitations and future directions are discussed.

PMID- 29636711
TI  - Openness to Changing Religious Views Is Related to Radial Diffusivity in the Genu
      of the Corpus Callosum in an Initial Study of Healthy Young Adults.
AB  - A quest orientation to religion is characterized by a search for answers to
      complex existential questions, a perception of religious doubt as positive, and
      an openness to change one's religious views as one grows and changes. This
      orientation is inversely related to fundamentalism, authoritarianism, and
      prejudice and directly related to cognitive complexity, openness to experience,
      and prosociality. To date, the neural correlates of religious quest have not been
      investigated. This study assessed the relationships between measures linked to
      white-matter integrity and quest religious orientation among 24 healthy
      participants using diffusion tensor imaging (DTI) and the quest scale. A tract
      based spatial statistical analysis whole-brain-corrected initially employing an
      accepted threshold (pTFCE < 0.05) and then applying a Bonferroni correction
      (pTFCE < 0.0042) identified a region of the genu of the corpus callosum as
      showing radial diffusivity measures being related to openness to change religious
      beliefs. When not employing a Bonferroni correction (pTFCE < 0.05), the openness
      to-change subscale of the quest scale negatively correlated with radial
      diffusivity and mean diffusivity measures in extensive white-matter regions in
      both hemispheres that include the corpus callosum body, genu, and splenium,
      superior longitudinal fasciculus, forceps minor, external capsule, and inferior
      fronto-occipital fasciculus. No relationships were found with the other
      subscales. These findings suggest that a greater openness to change one's
      religious views is associated with better white-matter integrity specifically in
      the genu of the corpus callosum and likely in a more extensive set of white
      matter structures interconnecting widespread cortical and subcortical regions in
      the brain across hemispheres. They, furthermore, suggest structural similarities
      that may link this tendency to associated positive psychological traits,
      including creative cognition and post-traumatic growth.

PMID- 29636712
TI  - The Optimal Starting Model to Search for the Accurate Growth Trajectory in Latent
      Growth Models.
AB  - This simulation study aims to propose an optimal starting model to search for the
      accurate growth trajectory in Latent Growth Models (LGM). We examine the
      performance of four different starting models in terms of the complexity of the
      mean and within-subject variance-covariance (V-CV) structures when there are time
      invariant covariates embedded in the population models. Results showed that the
      model search starting with the fully saturated model (i.e., the most complex mean
      and within-subject V-CV model) recovers best for the true growth trajectory in
      simulations. Specifically, the fully saturated starting model with using DeltaBIC
      and DeltaAIC performed best (over 95%) and recommended for researchers. An
      illustration of the proposed method is given using the empirical secondary
      dataset. Implications of the findings and limitations are discussed.

PMID- 29636713
TI  - Bilingual Contexts Modulate the Inhibitory Control Network.
AB  - The present functional magnetic resonance imaging (fMRI) study investigated
      influences of language contexts on inhibitory control and the underlying neural
      processes. Thirty Cantonese-Mandarin-English trilingual speakers, who were highly
      proficient in Cantonese (L1) and Mandarin (L2), and moderately proficient in
      English (L3), performed a picture-naming task in three dual-language contexts (L1
      L2, L2-L3, and L1-L3). After each of the three naming tasks, participants
      performed a flanker task, measuring contextual effects on the inhibitory control
      system. Behavioral results showed a typical flanker effect in the L2-L3 and L1-L3
      condition, but not in the L1-L2 condition, which indicates contextual
      facilitation on inhibitory control performance by the L1-L2 context. Whole brain
      analysis of the fMRI data acquired during the flanker tasks showed more neural
      activations in the right prefrontal cortex and subcortical areas in the L2-L3 and
      L1-L3 condition on one hand as compared to the L1-L2 condition on the other hand,
      suggesting greater involvement of the cognitive control areas when participants
      were performing the flanker task in L2-L3 and L1-L3 contexts. Effective
      connectivity analyses displayed a cortical-subcortical-cerebellar circuitry for
      inhibitory control in the trilinguals. However, contrary to the right-lateralized
      network in the L1-L2 condition, functional networks for inhibitory control in the
      L2-L3 and L1-L3 condition are less integrated and more left-lateralized. These
      findings provide a novel perspective for investigating the interaction between
      bilingualism (multilingualism) and inhibitory control by demonstrating instant
      behavioral effects and neural plasticity as a function of changes in global
      language contexts.

PMID- 29636714
TI  - The Role of Empathy and Life Satisfaction in Internet and Smartphone Use
      Disorder.
AB  - Recent studies have yielded initial evidence for an association between Internet
      Use Disorder (IUD), empathy, and life satisfaction. In the present study we
      sought to replicate these previous findings, and then to extend this research by
      also examining the relationship between empathy, life satisfaction, and the
      related phenomenon of Smartphone Use Disorder (SUD). The present study included
      independent samples from China (N = 612, 162 females) and Germany (N = 304, 207
      females), with the same set of questionnaires administered to both samples. IUD
      was measured with Pawlikowski's s-IAT and SUD was assessed with the short version
      of Kwon's Smartphone Addiction Scale. The Interpersonal Reactivity Index (IRI)
      was used to assess individual differences in empathy. Please note that for the
      German sample data on the empathy quotient (EQ) are also available. Life
      satisfaction data were collected using items from the SOEP-Questionnaire (Socio
      Economic Panel, Germany). In both of our samples we replicated previous findings
      showing the association between higher IUD, lower empathy, and lower life
      satisfaction scores. In addition, individuals with higher SUD showed higher
      scores on the IRI Personal Distress scale in China and Germany, while further
      associations between IRI dimensions and SUD were only found in the Chinese
      sample. Personal Distress is known to be highly correlated with the personality
      trait of Neuroticism, hence higher stress/negative emotionality in tense social
      situations is related to SUD. In the present study we confirm earlier findings
      showing the relationship between empathy, life satisfaction, and IUD, and extend
      some of these findings to SUD. We also emphasize the importance of cross-cultural
      studies when investigating IUD/SUD in the context of empathy and life
      satisfaction.

PMID- 29636715
TI  - Working Memory From the Psychological and Neurosciences Perspectives: A Review.
AB  - Since the concept of working memory was introduced over 50 years ago, different
      schools of thought have offered different definitions for working memory based on
      the various cognitive domains that it encompasses. The general consensus
      regarding working memory supports the idea that working memory is extensively
      involved in goal-directed behaviors in which information must be retained and
      manipulated to ensure successful task execution. Before the emergence of other
      competing models, the concept of working memory was described by the
      multicomponent working memory model proposed by Baddeley and Hitch. In the
      present article, the authors provide an overview of several working memory
      relevant studies in order to harmonize the findings of working memory from the
      neurosciences and psychological standpoints, especially after citing evidence
      from past studies of healthy, aging, diseased, and/or lesioned brains. In
      particular, the theoretical framework behind working memory, in which the related
      domains that are considered to play a part in different frameworks (such as
      memory's capacity limit and temporary storage) are presented and discussed. From
      the neuroscience perspective, it has been established that working memory
      activates the fronto-parietal brain regions, including the prefrontal, cingulate,
      and parietal cortices. Recent studies have subsequently implicated the roles of
      subcortical regions (such as the midbrain and cerebellum) in working memory.
      Aging also appears to have modulatory effects on working memory; age interactions
      with emotion, caffeine and hormones appear to affect working memory performances
      at the neurobiological level. Moreover, working memory deficits are apparent in
      older individuals, who are susceptible to cognitive deterioration. Another
      younger population with working memory impairment consists of those with mental,
      developmental, and/or neurological disorders such as major depressive disorder
      and others. A less coherent and organized neural pattern has been consistently
      reported in these disadvantaged groups. Working memory of patients with traumatic
      brain injury was similarly affected and shown to have unusual neural activity
      (hyper- or hypoactivation) as a general observation. Decoding the underlying
      neural mechanisms of working memory helps support the current theoretical
      understandings concerning working memory, and at the same time provides insights
      into rehabilitation programs that target working memory impairments from
      neurophysiological or psychological aspects.

PMID- 29636717
TI  - The Role of Type and Source of Uncertainty on the Processing of Climate Models
      Projections.
AB  - Scientists agree that the climate is changing due to human activities, but there
      is less agreement about the specific consequences and their timeline.
      Disagreement among climate projections is attributable to the complexity of
      climate models that differ in their structure, parameters, initial conditions,
      etc. We examine how different sources of uncertainty affect people's
      interpretation of, and reaction to, information about climate change by
      presenting participants forecasts from multiple experts. Participants viewed
      three types of sets of sea-level rise projections: (1) precise, but conflicting;
      (2) imprecise, but agreeing, and (3) hybrid that were both conflicting and
      imprecise. They estimated the most likely sea-level rise, provided a range of
      possible values and rated the sets on several features - ambiguity, credibility,
      completeness, etc. In Study 1, everyone saw the same hybrid set. We found that
      participants were sensitive to uncertainty between sources, but not to
      uncertainty about which model was used. The impacts of conflict and imprecision
      were combined for estimation tasks and compromised for feature ratings. Estimates
      were closer to the experts' original projections, and sets were rated more
      favorably under imprecision. Estimates were least consistent with (narrower than)
      the experts in the hybrid condition, but participants rated the conflicting set
      least favorably. In Study 2, we investigated the hybrid case in more detail by
      creating several distinct interval sets that combine conflict and imprecision.
      Two factors drive perceptual differences: overlap - the structure of the forecast
      set (whether intersecting, nested, tangent, or disjoint) - and asymmetry - the
      balance of the set. Estimates were primarily driven by asymmetry, and preferences
      were primarily driven by overlap. Asymmetric sets were least consistent with the
      experts: estimated ranges were narrower, and estimates of the most likely value
      were shifted further below the set mean. Intersecting and nested sets were rated
      similarly to imprecision, and ratings of disjoint and tangent sets were rated
      like conflict. Our goal was to determine which underlying factors of information
      sets drive perceptions of uncertainty in consistent, predictable ways. The two
      studies lead us to conclude that perceptions of agreement require intersection
      and balance, and overly precise forecasts lead to greater perceptions of
      disagreement and a greater likelihood of the public discrediting and
      misinterpreting information.

PMID- 29636716
TI  - Global Repetition Influences Contextual Cueing.
AB  - Our visual system has a striking ability to improve visual search based on the
      learning of repeated ambient regularities, an effect named contextual cueing.
      Whereas most of the previous studies investigated contextual cueing effect with
      the same number of repeated and non-repeated search displays per block, the
      current study focused on whether a global repetition frequency formed by
      different presentation ratios between the repeated and non-repeated
      configurations influence contextual cueing effect. Specifically, the number of
      repeated and non-repeated displays presented in each block was manipulated:
      12:12, 20:4, 4:20, and 4:4 in Experiments 1-4, respectively. The results revealed
      a significant contextual cueing effect when the global repetition frequency is
      high (>=1:1 ratio) in Experiments 1, 2, and 4, given that processing of repeated
      displays was expedited relative to non-repeated displays. Nevertheless, the
      contextual cueing effect reduced to a non-significant level when the repetition
      frequency reduced to 4:20 in Experiment 3. These results suggested that the
      presentation frequency of repeated relative to the non-repeated displays could
      influence the strength of contextual cueing. In other words, global repetition
      statistics could be a crucial factor to mediate contextual cueing effect.

PMID- 29636718
TI  - The Impact of Handedness, Sex, and Cognitive Abilities on Left-Right
      Discrimination: A Behavioral Study.
AB  - The present study examined the relationship between left-right discrimination
      (LRD) performance and handedness, sex and cognitive abilities. In total, 31 men
      and 35 women - with a balanced ratio of left-and right-handers - completed the
      Bergen Left-Right Discrimination Test. We found an advantage of left-handers in
      both identifying left hands and in verifying "left" propositions. A sex effect
      was also found, as women had an overall higher error rate than men, and
      increasing difficulty impacted their reaction time more than it did for men.
      Moreover, sex interacted with handedness and manual preference strength. A
      negative correlation of LRD reaction time with visuo-spatial and verbal long-term
      memory was found independently of sex, providing new insights into the
      relationship between cognitive skills and performance on LRD.

PMID- 29636719
TI  - The Influence of Second Language (L2) Proficiency on Cognitive Control Among
      Young Adult Unbalanced Chinese-English Bilinguals.
AB  - The current study investigates the influence of L2 proficiency on cognitive
      control among three matched groups of unbalanced Chinese-English bilinguals.
      Flanker task was administered to measure conflict monitoring and inhibition, and
      Wisconsin Card Sorting Test (WCST) to measure mental set shifting. ANOVA analyses
      of the Flanker results showed no differences in inhibition across all groups and
      no interaction between group and condition. However, the Flanker results showed
      faster performance for the highest L2 proficiency group relative to the lowest L2
      proficiency group in all conditions (incongruent, neutral, and congruent), which
      reflects better ability of conflict monitoring. Finally, ANOVA analyses of the
      WCST results showed no differences across all groups. These results altogether
      suggest that L2 proficiency has significant influence on cognitive control, but
      only in conflict monitoring, not in inhibition or mental set shifting.

PMID- 29636720
TI  - The Importance of Protesters' Morals: Moral Obligation as a Key Variable to
      Understand Collective Action.
AB  - Collective action and protest have become a normalized political behavior that in
      many cases defines the political agenda. The reasons why people take to the
      streets constitute a central subject within the study of social psychology. In
      the literature, three precedents of protest that have been established as central
      to the study of this phenomenon are: injustice, efficacy, and identity. But
      political action is also deeply related to moral values. This explains why in
      recent years some moral constructs have also been pointed out as predictors of
      collective action. Moral variables have been introduced into the literature with
      little consideration to how they relate to each other. Thus, work in this
      direction is needed. The general aim of this research is to differentiate moral
      obligation from moral norms and moral conviction, as well as to compare their
      ability to predict collective action. In order to do so, the research objectives
      are: (a) conceptualize and operationalize moral obligation (Study 1, N = 171);
      (b) test its predictive power for intention to participate in protests (Study 2,
      N = 622); and (c) test moral obligation in a real context (Study 3, N = 407).
      Results are encouraging, showing not only that moral obligation is different to
      moral conviction and moral norm, but also that it is a more effective predictor
      working both for intention and real participation. This work therefore presents
      moral obligation as a key precedent of protest participation, prompting its
      future use as a variable that can enhance existing predictive models of
      collective action. Results regarding other variables are also discussed.

PMID- 29636721
TI  - Heparin: The Silver Bullet of Aneurysmal Subarachnoid Hemorrhage?
AB  - Various neurological diseases have recently been associated with
      neuroinflammation and worsening outcomes. Subarachnoid hemorrhage has been shown
      to generate a potent neuroinflammatory response. Heparin is a potential effective
      anti-inflammatory agent to prevent initial injury as well as delayed neurological
      decline. Different mechanisms of action for heparin have been proposed including,
      but not limited to the binding and neutralization of oxyhemoglobin, decreased
      transcription and signal transduction of endothelin-1, inhibition of binding to
      vessel wall selectins and vascular leakage into the subarachnoid space as well as
      direct binding and neutralization of inflammatory molecules. With a reasonably
      safe side-effect profile, heparin has shown significant promise in small series
      in human studies of aneurysmal subarachnoid hemorrhage in decreasing both initial
      and delayed neurological injury. Further studies are needed to validate various
      neuroprotective features of heparin in subarachnoid hemorrhage as well as other
      disease states.

PMID- 29636722
TI  - The Neurocognitive and MRI Outcomes of West Nile Virus Infection: Preliminary
      Analysis Using an External Control Group.
AB  - To understand the long-term neurological outcomes resultant of West Nile virus
      (WNV) infection, participants from a previously established, prospective WNV
      cohort were invited to take part in a comprehensive neurologic and neurocognitive
      examination. Those with an abnormal exam finding were invited for MRI to evaluate
      cortical thinning and regional brain atrophy following infection. Correlations of
      presenting clinical syndrome with neurologic and neurocognitive dysfunctions were
      evaluated, as well as correlations of neurocognitive outcomes with MRI results.
      From 2002 to 2012, a total of 262 participants with a history of WNV infection
      were enrolled as research participants in a longitudinal cohort study, and 117
      completed comprehensive neurologic and neurocognitive evaluations. Abnormal
      neurological exam findings were identified in 49% (57/117) of participants, with
      most abnormalities being unilateral. The most common abnormalities included
      decreased strength (26%; 30/117), abnormal reflexes (14%; 16/117), and tremors
      (10%; 12/117). Weakness and decreased reflexes were consistent with lower motor
      neuron damage in a significant proportion of patients. We observed a 22% overall
      rate of impairment on the Repeatable Battery for the Assessment of
      Neuropsychological Status (RBANS), with impairments observed in immediate (31%)
      and delayed memory (25%). On MRI, participants showed significant cortical
      thinning as compared to age- and gender-matched controls in both hemispheres,
      with affected regions primarily occurring in the frontal and limbic cortices.
      Regional atrophy occurred in the cerebellum, brain stem, thalamus, putamen, and
      globus pallidus. This study provides valuable new information regarding the
      neurological outcomes following WNV infection, with MRI evidence of significant
      cortical thinning and regional atrophy; however, it is important to note that the
      results may include systemic bias due to the external control group. Considering
      no effective treatment measures are available, strategies to prevent infection
      are key.

PMID- 29636723
TI  - Environmental Subconcussive Injury, Axonal Injury, and Chronic Traumatic
      Encephalopathy.
AB  - Brain injury occurs in two phases: the initial injury itself and a secondary
      cascade of precise immune-based neurochemical events. The secondary phase is
      typically functional in nature and characterized by delayed axonal injury with
      more axonal disconnections occurring than in the initial phase. Axonal injury
      occurs across the spectrum of disease severity, with subconcussive injury,
      especially when repetitive, now considered capable of producing significant
      neurological damage consistent with axonal injury seen in clinically evident
      concussion, despite no observable symptoms. This review is the first to introduce
      the concept of environmental subconcussive injury (ESCI) and sets out how
      secondary brain damage from ESCI once past the juncture of microglial activation
      appears to follow the same neuron-damaging pathway as secondary brain damage from
      conventional brain injury. The immune response associated with ESCI is strikingly
      similar to that mounted after conventional concussion. Specifically, microglial
      activation is followed closely by glutamate and calcium flux, excitotoxicity,
      reactive oxygen species and reactive nitrogen species (RNS) generation, lipid
      peroxidation, and mitochondrial dysfunction and energy crisis. ESCI damage also
      occurs in two phases, with the primary damage coming from microbiome injury (due
      to microbiome-altering events) and secondary damage (axonal injury) from
      progressive secondary neurochemical events. The concept of ESCI and the
      underlying mechanisms have profound implications for the understanding of chronic
      traumatic encephalopathy (CTE) etiology because it has previously been suggested
      that repetitive axonal injury may be the primary CTE pathogenesis in susceptible
      individuals and it is best correlated with lifetime brain trauma load. Taken
      together, it appears that susceptibility to brain injury and downstream
      neurodegenerative diseases, such as CTE, can be conceptualized as a continuum of
      brain resilience. At one end is optimal resilience, capable of launching
      effective responses to injury with spontaneous recovery, and at the other end is
      diminished resilience with a compromised ability to respond and/or heal
      appropriately. Modulating factors such as one's total cumulative and synergistic
      brain trauma load, bioavailability of key nutrients needed for proper functioning
      of restorative metabolic pathways (specifically those involved in the
      deactivation and clearance of metabolic by-products of brain injury) are key to
      ultimately determining one's brain resilience.

PMID- 29636724
TI  - Sport-Related Concussion Alters Indices of Dynamic Cerebral Autoregulation.
AB  - Sport-related concussion is known to affect a variety of brain functions.
      However, the impact of this brain injury on cerebral autoregulation (CA) is
      poorly understood. Thus, the goal of the current study was to determine the acute
      and cumulative effects of sport-related concussion on indices of dynamic CA.
      Toward this end, 179 elite, junior-level (age 19.6 +/- 1.5 years) contact sport
      (ice hockey, American football) athletes were recruited for preseason testing, 42
      with zero prior concussions and 31 with three or more previous concussions.
      Eighteen athletes sustained a concussion during that competitive season and
      completed follow-up testing at 72 h, 2 weeks, and 1 month post injury. Beat-by
      beat arterial blood pressure (BP) and middle cerebral artery blood velocity
      (MCAv) were recorded using finger photoplethysmography and transcranial Doppler
      ultrasound, respectively. Five minutes of repetitive squat-stand maneuvers
      induced BP oscillations at 0.05 and 0.10 Hz (20- and 10-s cycles, respectively).
      The BP-MCAv relationship was quantified using transfer function analysis to
      estimate Coherence (correlation), Gain (amplitude ratio), and Phase (timing
      offset). At a group level, repeated-measures ANOVA indicated that 0.10 Hz Phase
      was significantly reduced following an acute concussion, compared to preseason,
      by 23% (-0.136 +/- 0.033 rads) at 72 h and by 18% (-0.105 +/- 0.029 rads) at 2
      weeks post injury, indicating impaired autoregulatory functioning; recovery to
      preseason values occurred by 1 month. Athletes were cleared to return to
      competition after a median of 14 days (range 7-35), implying that physiologic
      dysfunction persisted beyond clinical recovery in many cases. When comparing
      dynamic pressure buffering between athletes with zero prior concussions and those
      with three or more, no differences were observed. Sustaining an acute sport
      related concussion induces transient impairments in the capabilities of the
      cerebrovascular pressure-buffering system that may persist beyond 2 weeks and may
      be due to a period of autonomic dysregulation. Athletes with a history of three
      or more concussions did not exhibit impairments relative to those with zero prior
      concussions, suggesting recovery of function over time. Findings from this study
      support the potential need to consider physiological recovery in deciding when
      patients should return to play following a concussion.

PMID- 29636725
TI  - Melatonin Absence Leads to Long-Term Leptin Resistance and Overweight in Rats.
AB  - Melatonin (Mel), a molecule that conveys photoperiodic information to the
      organisms, is also involved in the regulation of energy homeostasis. Mechanisms
      of action of Mel in the energy balance remain unclear; herein we investigated how
      Mel regulates energy intake and expenditure to promote a proper energy balance.
      Male Wistar rats were assigned to control, control + Mel, pinealectomized (PINX)
      and PINX + Mel groups. To restore a 24-h rhythm, Mel (1 mg/kg) was added to the
      drinking water exclusively during the dark phase for 13 weeks. After this
      treatment period, rats were subjected to a 24-h fasting test, an acute leptin
      responsiveness test and cold challenge. Mel treatment reduced food intake, body
      weight, and adiposity. When challenged to 24-h fasting, Mel-treated rats also
      showed reduced hyperphagia when the food was replaced. Remarkably, PINX rats
      exhibited leptin resistance; this was likely related to the capacity of leptin to
      affect body weight, food intake, and hypothalamic signal-transducer and activator
      of transcription 3 phosphorylation, all of which were reduced. Mel treatment
      restored leptin sensitivity in PINX rats. An increased hypothalamic expression of
      agouti-related peptide (Agrp), neuropeptide Y, and Orexin was observed in the
      PINX group while Mel treatment reduced the expression of Agrp and Orexin. In
      addition, PINX rats presented lower UCP1 protein levels in the brown adipose
      tissue and required higher tail vasoconstriction to get a proper thermogenic
      response to cold challenge. Our findings reveal a previously unrecognized
      interaction of Mel and leptin in the hypothalamus to regulate the energy balance.
      These findings may help to explain the high incidence of metabolic diseases in
      individuals exposed to light at night.

PMID- 29636726
TI  - Growth Hormone Overexpression Disrupts Reproductive Status Through Actions on
      Leptin.
AB  - Growth and reproduction are closely related. Growth hormone (GH)-transgenic
      common carp exhibit accelerated growth and delayed reproductive development,
      which provides an amenable model to study hormone cross talk between the growth
      and reproductive axes. We analyzed the energy status and reproductive development
      in GH-transgenic common carp by using multi-tissue RNA sequencing, real-time-PCR,
      Western blotting, ELISA, immunofluorescence, and in vitro incubation. The
      expression of gys (glycogen synthase) and igfbp1 (insulin-like growth factor
      binding protein) as well as blood glucose concentrations are lower in GH
      transgenic carp. Agrp1 (agouti-related protein 1) and sla (somatolactin a), which
      are related to appetite and lipid catabolism, are significantly higher in GH
      transgenic carp. Low glucose content and increased appetite indicate disrupted
      metabolic and energy deprivation status in GH-transgenic carp. Meanwhile, the
      expression of genes, such as gnrhr2 (gonadotropin-releasing hormone receptor 2),
      gthalpha (gonadotropin hormone, alpha polypeptide), fshbeta (follicle stimulating
      hormone, beta polypeptide), lhbeta [luteinizing hormone, beta polypeptide] in the
      pituitary, cyp19a1a (aromatase A) in the gonad, and cyp19a1b (aromatase B) in the
      hypothalamus, are decreased in GH-transgenic carp. In contrast, pituitary gnih
      (gonadotropin inhibitory hormone), drd1 (dopamine receptor D1), drd3 (dopamine
      receptor D3), and drd4 (dopamine receptor D4) exhibit increased expression, which
      were associated with the retarded reproductive development. Leptin receptor mRNA
      was detected by fluorescence in situ hybridization in the pituitary including the
      pars intermedia and proximal pars distalis, suggesting a direct effect of leptin
      on LH. Recombinant carp Leptin protein was shown to stimulate pituitary gthalpha,
      fshbeta, lhbeta expression, and ovarian germinal vesicle breakdown in vitro. In
      addition to neuroendocrine factors, we suggest that reduced hepatic leptin
      signaling to the pituitary might be part of the response to overexpression of GH
      and the resulting delay in puberty onset.

PMID- 29636727
TI  - Niche Separation Increases With Genetic Distance Among Bloom-Forming
      Cyanobacteria.
AB  - Bacterial communities are composed of distinct groups of potentially interacting
      lineages, each thought to occupy a distinct ecological niche. It remains unclear,
      however, how quickly niche preference evolves and whether more closely related
      lineages are more likely to share ecological niches. We addressed these questions
      by following the dynamics of two bloom-forming cyanobacterial genera over an 8
      year time-course in Lake Champlain, Canada, using 16S amplicon sequencing and
      measurements of several environmental parameters. The two genera, Microcystis (M)
      and Dolichospermum (D), are frequently observed simultaneously during bloom
      events and thus have partially overlapping niches. However, the extent of their
      niche overlap is debated, and it is also unclear to what extent niche
      partitioning occurs among strains within each genus. To identify strains within
      each genus, we applied minimum entropy decomposition (MED) to 16S rRNA gene
      sequences. We confirmed that at a genus level, M and D have different preferences
      for nitrogen and phosphorus concentrations. Within each genus, we also identified
      strains differentially associated with temperature, precipitation, and
      concentrations of nutrients and toxins. In general, niche similarity between
      strains (as measured by co-occurrence over time) declined with genetic distance.
      This pattern is consistent with habitat filtering - in which closely related taxa
      are ecologically similar, and therefore tend to co-occur under similar
      environmental conditions. In contrast with this general pattern, similarity in
      certain niche dimensions (notably particulate nitrogen and phosphorus) did not
      decline linearly with genetic distance, and instead showed a complex polynomial
      relationship. This observation suggests the importance of processes other than
      habitat filtering - such as competition between closely related taxa, or
      convergent trait evolution in distantly related taxa - in shaping particular
      traits in microbial communities.

PMID- 29636728
TI  - Environmental Stability and Infectivity of Hepatitis C Virus (HCV) in Different
      Human Body Fluids.
AB  - Background: Hepatitis C virus (HCV) is a hepatotropic, blood-borne virus, but in
      up to one-third of infections of the transmission route remained unidentified.
      Viral genome copies of HCV have been identified in several body fluids, however,
      non-parental transmission upon exposure to contaminated body fluids seems to be
      rare. Several body fluids, e.g., tears and saliva, are renowned for their
      antimicrobial and antiviral properties, nevertheless, HCV stability has never
      been systematically analyzed in those fluids. Methods: We used state of the art
      infectious HCV cell culture techniques to investigate the stability of HCV in
      different body fluids to estimate the potential risk of transmission via patient
      body fluid material. In addition, we mimicked a potential contamination of HCV in
      tear fluid and analyzed which impact commercially available contact lens
      solutions might have in such a scenario. Results: We could demonstrate that HCV
      remains infectious over several days in body fluids like tears, saliva, semen,
      and cerebrospinal fluid. Only hydrogen-peroxide contact lens solutions were able
      to efficiently inactivate HCV in a suspension test. Conclusion: These results
      indicate that HCV, once it is present in various body fluids of infected
      patients, remains infective and could potentially contribute to transmission upon
      direct contact.

PMID- 29636729
TI  - Involvement of hrpX and hrpG in the Virulence of Acidovorax citrulli Strain Aac5,
      Causal Agent of Bacterial Fruit Blotch in Cucurbits.
AB  - Acidovorax citrulli causes bacterial fruit blotch, a disease that poses a global
      threat to watermelon and melon production. Despite its economic importance,
      relatively little is known about the molecular mechanisms of pathogenicity and
      virulence of A. citrulli. Like other plant-pathogenic bacteria, A. citrulli
      relies on a type III secretion system (T3SS) for pathogenicity. On the basis of
      sequence and operon arrangement analyses, A. citrulli was found to have a class
      II hrp gene cluster similar to those of Xanthomonas and Ralstonia spp. In the
      class II hrp cluster, hrpG and hrpX play key roles in the regulation of T3SS
      effectors. However, little is known about the regulation of the T3SS in A.
      citrulli. This study aimed to investigate the roles of hrpG and hrpX in A.
      citrulli pathogenicity. We found that hrpG or hrpX deletion mutants of the A.
      citrulli group II strain Aac5 had reduced pathogenicity on watermelon seedlings,
      failed to induce a hypersensitive response in tobacco, and elicited higher levels
      of reactive oxygen species in Nicotiana benthamiana than the wild-type strain.
      Additionally, we demonstrated that HrpG activates HrpX in A. citrulli. Moreover,
      transcription and translation of the type 3-secreted effector (T3E) gene
      Aac5_2166 were suppressed in hrpG and hrpX mutants. Notably, hrpG and hrpX
      appeared to modulate biofilm formation. These results suggest that hrpG and hrpX
      are essential for pathogenicity, regulation of T3Es, and biofilm formation in A.
      citrulli.

PMID- 29636730
TI  - Potential Biological and Climatic Factors That Influence the Incidence and
      Persistence of Highly Pathogenic H5N1 Avian Influenza Virus in Egypt.
AB  - Highly pathogenic H5N1 avian influenza virus (A/H5N1) of clade 2.2.1 is endemic
      in poultry in Egypt where the highest number of human infections worldwide was
      reported. During the last 12 years the Egyptian A/H5N1 evolved into several
      genotypes. In 2007-2014 vaccinated poultry suffered from antigenic drift variants
      of clade 2.2.1.1 and in 2014/2015 an unprecedented upsurge of A/H5N1 clade
      2.2.1.2 occurred in poultry and humans. Factors contributing to the endemicity or
      re-emergence of A/H5N1 in poultry in Egypt remain unclear. Here, three potential
      factors were studied: climatic factors (temperature, relative humidity, and wind
      speed), biological fitness in vitro, and pathogenicity in domestic Pekin and
      Muscovy ducks. Statistical analyses using negative binomial regression models
      indicated that ambient temperature in winter months influenced the spread of
      A/H5N1 in different geographic areas analyzed in this study. In vitro, at 4 and
      56 degrees C 2.2.1.1 and recent 2.2.1.2 viruses were more stable than other
      viruses used in this study. Further, Pekin ducks were more resistant than Muscovy
      ducks and the viruses were excreted for up to 2 weeks post-infection assuming a
      strong role as a reservoir. Taken together, ambient temperature in winter months
      potentially contributes to increasing outbreaks in some regions in Egypt. Heat
      stability of clade 2.2.1.1 and recent 2.2.1.2 viruses probably favors their
      persistence at elevated temperatures. Importantly, asymptomatically infected
      Pekin ducks may play an important role in the spread of avian and human-like
      A/H5N1 in Egypt. Therefore, control measures including targeted surveillance and
      culling of silently infected Pekin ducks should be considered.

PMID- 29636731
TI  - Performance of Molecular Approaches for Aspergillus Detection and Azole
      Resistance Surveillance in Cystic Fibrosis.
AB  - Aspergillus fumigatus triazole resistance is an emerging concern for treating
      chronically infected/colonized patients. This study sought to evaluate the
      performance of PCR assays to detect Aspergillus fungi together with azole
      resistance in sputum samples from cystic fibrosis (CF) patients. In total, 119
      sputum samples from 87 CF patients were prospectively processed for Aspergillus
      detection by means of mycological culture and four qPCR assays, 2 in-house
      methods and two commercial multiplex real-time PCR assays simultaneously
      detecting Aspergillus and the most relevant cyp51A gene mutations (MycoGENIE(r)
      and AsperGenius(r)). Azole susceptibility of A. fumigatus isolates was assessed
      using Etest(r) method and cyp51A gene mutation were characterized by sequencing.
      The overall rate of Aspergillus detection with the four qPCR assays ranged from
      47.9 to 57.1%, contrasting with 42/119 (35.3%) positive cultures with A.
      fumigatus. The high sensitivity of PCR on sputum could then contribute to more
      effective grading of Aspergillus disease in CF patients. Five out of 41 isolated
      strains (12.2%) exhibited azole-resistant MIC patterns, three of which harbored
      cyp51A mutations and only 1/3 with the sequence TR34/L98H. Combined with culture,
      PCR assay achieved high sensitivity Aspergillus screening in CF samples. However,
      cyp51A targeting was only moderately effective for azole resistance monitoring,
      while Aspergillus resistance remains of great concern.

PMID- 29636732
TI  - Identification of Plasmid-Encoded sRNAs in a blaNDM-1-Harboring Multidrug
      Resistance Plasmid pNDM-HK in Enterobacteriaceae.
AB  - Small RNAs (sRNAs) play significant roles in regulating gene expression post
      transcriptionally in response to environmental changes in bacteria. In this work,
      we identified and characterized six novel sRNAs from an emerging multidrug
      resistance (MDR) plasmid pNDM-HK, a New Delhi metallo-beta-lactamase 1 gene
      (blaNDM-1)-carrying IncL/M plasmid that has caused worldwide threat in recent
      years. These sRNAs are located at different regions of pNDM-HK, such as
      replication, stability, and variable regions. Moreover, one of the plasmid
      encoded sRNAs (NDM-sR3) functions in an Hfq-dependent manner and possibly plays
      roles in the fitness of pNDM-HK carrying bacteria. In addition, we attempted to
      construct the phylogenetic tree based on these novel sRNAs and surprisingly, the
      sRNA-phylogenetic tree provided significant information about the evolutionary
      pathway of pNDM-HK, including possible gene acquisition and insertion from
      relevant plasmids. Moreover, the sRNA-phylogenetic tree can specifically cluster
      the IncM2 type and distinguish it from other IncL/M subtypes. In summary, this is
      the first study to systematically identify and characterize sRNAs from clinically
      isolated MDR plasmids. We believe that these newly found sRNAs could lead to
      further understanding and new directions to study the evolution and dissemination
      of the clinically MDR bacterial plasmids.

PMID- 29636733
TI  - Diversity and Antibiotic Susceptibility of Acinetobacter Strains From Milk Powder
      Produced in Germany.
AB  - Forty-seven Acinetobacter spp. isolates from milk powder obtained from a powdered
      milk producer in Germany were investigated for their antibiotic resistance
      susceptibilities, in order to assess whether strains from food harbor multiple
      antibiotic resistances and whether the food route is important for dissemination
      of resistance genes. The strains were identified by 16S rRNA and rpoB gene
      sequencing, as well as by whole genome sequencing of selected isolates and their
      in silico DNA-DNA hybridization (DDH). Furthermore, they were genotyped by rep
      PCR together with reference strains of pan-European groups I, II, and III strains
      of Acinetobacter baumannii. Of the 47 strains, 42 were identified as A.
      baumannii, 4 as Acinetobacter Pittii, and 1 as Acinetobacter calcoaceticus based
      on 16S rRNA gene sequencing. In silico DDH with the genome sequence data of
      selected strains and rpoB gene sequencing data suggested that the five non-A.
      baumannii strains all belonged to A. pittii, suggesting that the rpoB gene is
      more reliable than the 16S rRNA gene for species level identification in this
      genus. Rep-PCR genotyping of the A. baumannii strains showed that these could be
      grouped into four groups, and that some strains clustered together with reference
      strains of pan-European clinical group II and III strains. All strains in this
      study were intrinsically resistant toward chloramphenicol and oxacillin, but
      susceptible toward tetracycline, tobramycin, erythromycin, and ciprofloxacin. For
      cefotaxime, 43 strains (91.5%) were intermediate and 3 strains (6.4%) resistant,
      while 3 (6.4%) and 21 (44.7%) strains exhibited resistance to cefepime and
      streptomycin, respectively. Forty-six (97.9%) strains were susceptible to
      amikacin and ampicillin-sulbactam. Therefore, the strains in this study were
      generally not resistant to the clinically relevant antibiotics, especially
      tobramycin, ciprofloxacin, cefepime, and meropenem, suggesting that the food
      route probably poses only a low risk for multidrug resistant Acinetobacter
      strains or resistance genes.

PMID- 29636734
TI  - Retrospective Analysis of Bacterial Cultures Sampled in German Chicken-Fattening
      Farms During the Years 2011-2012 Revealed Additional VIM-1 Carbapenemase
      Producing Escherichia coli and a Serologically Rough Salmonella enterica Serovar
      Infantis.
AB  - Carbapenems are last-resort antibiotics used in human medicine. The increased
      detection of carbapenem-resistant Enterobacteriaceae (CRE) is therefore worrying.
      In 2011 we reported the first livestock-associated VIM-1-producing Salmonella
      (S.) enterica serovar Infantis (R3) isolate from dust, sampled in a German
      chicken fattening farm. Due to this observation we retrospectively investigated
      more than 536 stored bacterial cultures, isolated from 45 chicken fattening farms
      during the years 2011 and 2012. After a non-selective overnight incubation, the
      bacteria were transferred to selective media. Escherichia (E.) coli and
      Salmonella growing on these media were further investigated, including antibiotic
      susceptibility testing, carbapenemase gene screening and whole genome sequencing
      (WGS). In total, four CRE were found in three out of 45 investigated farms:
      Besides R3, one additional Salmonella (G-336-1a) as well as two E. coli isolates
      (G-336-2, G-268-2). All but G-268-2 harbored the blaVIM-1 gene. Salmonella
      isolates R3 and G-336-1 were closely related although derived from two different
      farms. All three blaVIM-1-encoding isolates possessed identical plasmids and the
      blaVIM-1- containing transposon showed mobility at least in vitro. In isolate G
      268-2, the AmpC beta-lactamase gene blaCMY-2 but no known carbapenemase gene was
      identified. However, a transfer of the phenotypic resistance was possible.
      Furthermore, G-268-2 contained the mcr-1 gene, combining phenotypical carbapenem-
      as well as colistin resistance in one isolate. Carbapenem-resistant
      Enterobacteriaceae have been found in three out of 45 investigated chicken
      flocks. This finding is alarming and emphasizes the importance of intervention
      strategies to contain the environmental spread of resistant bacteria in animals
      and humans.

PMID- 29636735
TI  - High Variability in Cellular Stoichiometry of Carbon, Nitrogen, and Phosphorus
      Within Classes of Marine Eukaryotic Phytoplankton Under Sufficient Nutrient
      Conditions.
AB  - Current hypotheses suggest that cellular elemental stoichiometry of marine
      eukaryotic phytoplankton such as the ratios of cellular
      carbon:nitrogen:phosphorus (C:N:P) vary between phylogenetic groups. To
      investigate how phylogenetic structure, cell volume, growth rate, and temperature
      interact to affect the cellular elemental stoichiometry of marine eukaryotic
      phytoplankton, we examined the C:N:P composition in 30 isolates across 7 classes
      of marine phytoplankton that were grown with a sufficient supply of nutrients and
      nitrate as the nitrogen source. The isolates covered a wide range in cell volume
      (5 orders of magnitude), growth rate (<0.01-0.9 d-1), and habitat temperature (2
      24 degrees C). Our analysis indicates that C:N:P is highly variable, with
      statistical model residuals accounting for over half of the total variance and no
      relationship between phylogeny and elemental stoichiometry. Furthermore, our data
      indicated that variability in C:P, N:P, and C:N within Bacillariophyceae
      (diatoms) was as high as that among all of the isolates that we examined. In
      addition, a linear statistical model identified a positive relationship between
      diatom cell volume and C:P and N:P. Among all of the isolates that we examined,
      the statistical model identified temperature as a significant factor, consistent
      with the temperature-dependent translation efficiency model, but temperature only
      explained 5% of the total statistical model variance. While some of our results
      support data from previous field studies, the high variability of elemental
      ratios within Bacillariophyceae contradicts previous work that suggests that this
      cosmopolitan group of microalgae has consistently low C:P and N:P ratios in
      comparison with other groups.

PMID- 29636737
TI  - Pentocin MQ1: A Novel, Broad-Spectrum, Pore-Forming Bacteriocin From
      Lactobacillus pentosus CS2 With Quorum Sensing Regulatory Mechanism and
      Biopreservative Potential.
AB  - Micrococcus luteus, Listeria monocytogenes, and Bacillus cereus are major food
      borne pathogenic and spoilage bacteria. Emergence of antibiotic resistance and
      consumer demand for foods containing less of chemical preservatives led to a
      search for natural antimicrobials. A study aimed at characterizing, investigating
      the mechanism of action and regulation of biosynthesis and evaluating the
      biopreservative potential of pentocin from Lactobacillus pentosus CS2 was
      conducted. Pentocin MQ1 is a novel bacteriocin isolated from L. pentosus CS2 of
      coconut shake origin. The purification strategy involved adsorption-desorption of
      bacteriocin followed by RP-HPLC. It has a molecular weight of 2110.672 Da as
      determined by MALDI-TOF mass spectrometry and a molar extinction value of 298.82
      M-1 cm-1. Pentocin MQ1 is not plasmid-borne and its biosynthesis is regulated by
      a quorum sensing mechanism. It has a broad spectrum of antibacterial activity,
      exhibited high chemical, thermal and pH stability but proved sensitive to
      proteolytic enzymes. It is potent against M. luteus, B. cereus, and L.
      monocytogenes at micromolar concentrations. It is quick-acting and exhibited a
      bactericidal mode of action against its targets. Target killing was mediated by
      pore formation. We report for the first time membrane permeabilization as a
      mechanism of action of the pentocin from the study against Gram-positive
      bacteria. Pentocin MQ1 is a cell wall-associated bacteriocin. Application of
      pentocin MQ1 improved the microbiological quality and extended the shelf life of
      fresh banana. This is the first report on the biopreservation of banana using
      bacteriocin. These findings place pentocin MQ1 as a potential biopreservative for
      further evaluation in food and medical applications.

PMID- 29636738
TI  - A Versatile New Model of Chemically Induced Chronic Colitis Using an Outbred
      Murine Strain.
AB  - Murine colitis models are crucial tools for understanding intestinal homeostasis
      and inflammation. However, most current models utilize a highly inbred strain of
      mice, and often only one sex is employed to limit bias. This targeted approach,
      which in itself is biased, means that murine genetic diversity and sex-related
      differences are ignored, making it even more difficult to extend findings to
      humans, who are highly heterogeneous. Furthermore, most models do not examine the
      chronic form of colitis, an important fact taking into account the chronic nature
      of the inflammatory bowel diseases (IBD). Here, we attempted to create a more
      realistic murine colitis model by addressing these three issues. Using chemically
      induced chronic colon inflammation in an outbred strain of mice (RjOrl:SWISS [CD
      1]), we (i) mimicked the relapsing nature of the disease, (ii) better represented
      normal genetic variability, and (iii) employed both female and male mice. Colitis
      was induced by intrarectal administration of dinitrobenzene sulfonic acid (DNBS).
      After a recovery period and 3 days before the mice were euthanized, colitis was
      reactivated by a second administration of DNBS. Protocol length was 24 days.
      Colitis severity was assessed using body mass, macroscopic scores, and
      histological scores. Myeloperoxidase (MPO) activity, cytokine levels, and
      lymphocyte populations were also characterized. Our results show that the
      intrarectal administration of DNBS effectively causes colitis in both female and
      male CD-1 mice in a dose-dependent manner, as reflected by loss of body mass,
      macroscopic scores and histological scores. Furthermore, colon cytokine levels
      and mesenteric lymph node characteristics indicate that this model involves
      immune system activation. Although some variables were sex-specific, most of the
      results support including both females and males in the model. Our ultimate goal
      is to make this model available to researchers for testing candidate anti
      inflammatory agents, such as classical or next-generation probiotics; we also aim
      for the results to be more easily transferrable to human trials.

PMID- 29636736
TI  - Bacterial Symbionts in Lepidoptera: Their Diversity, Transmission, and Impact on
      the Host.
AB  - The insect's microbiota is well acknowledged as a "hidden" player influencing
      essential insect traits. The gut microbiome of butterflies and moths
      (Lepidoptera) has been shown to be highly variable between and within species,
      resulting in a controversy on the functional relevance of gut microbes in this
      insect order. Here, we aim to (i) review current knowledge on the composition of
      gut microbial communities across Lepidoptera and (ii) elucidate the drivers of
      the variability in the lepidopteran gut microbiome and provide an overview on
      (iii) routes of transfer and (iv) the putative functions of microbes in
      Lepidoptera. To find out whether Lepidopterans possess a core gut microbiome, we
      compared studies of the microbiome from 30 lepidopteran species. Gut bacteria of
      the Enterobacteriaceae, Bacillaceae, and Pseudomonadaceae families were the most
      widespread across species, with Pseudomonas, Bacillus, Staphylococcus,
      Enterobacter, and Enterococcus being the most common genera. Several studies
      indicate that habitat, food plant, and age of the host insect can greatly impact
      the gut microbiome, which contributes to digestion, detoxification, or defense
      against natural enemies. We mainly focus on the gut microbiome, but we also
      include some examples of intracellular endosymbionts. These symbionts are present
      across a broad range of insect taxa and are known to exert different effects on
      their host, mostly including nutrition and reproductive manipulation. Only two
      intracellular bacteria genera (Wolbachia and Spiroplasma) have been reported to
      colonize reproductive tissues of Lepidoptera, affecting their host's
      reproduction. We explore routes of transmission of both gut microbiota and
      intracellular symbionts and have found that these microbes may be horizontally
      transmitted through the host plant, but also vertically via the egg stage. More
      detailed knowledge about the functions and plasticity of the microbiome in
      Lepidoptera may provide novel leads for the control of lepidopteran pest species.

PMID- 29636739
TI  - Incidence and Outbreak of Healthcare-Onset Healthcare-Associated Clostridioides
      difficile Infections Among Intensive Care Patients in a Large Teaching Hospital
      in China.
AB  - Background:Clostridioides difficile infection (CDI) is an important cause of
      morbidity and mortality among hospitalized patients. In China, however, hospital
      staff do not routinely test for CDI, leading to under-diagnosis and poor patient
      outcomes. Locally generated CDI data can help assess the magnitude of the problem
      and strengthen approaches for CDI prevention and control. Methods: We
      prospectively monitored hospital-onset hospital-associated (HOHA) CDI in four
      intensive care units (ICUs) from June 2013 to September 2014 in a large teaching
      hospital in China. We collected clinical information from all ICU patients with
      >= 3 episodes of diarrhea occurring within a 24-h period at least 48 h following
      admission (suspect case definition). Stool specimens were collected from all
      suspect cases of CDI and cultured for C. difficile. Polymerase chain reaction
      (PCR) was used to detect toxin genes from positive isolates; multi-locus sequence
      typing (MLST) was used for typing and identifying novel strains. We estimated the
      incidence rate as the number of HOHA CDI cases per 10,000 patient days; 95%
      confidence intervals were generated to assess rate differences between the four
      ICUs. Results: A total of 593 hospital-onset diarrhea patients met the suspect
      case definition during the study period. Of these, 47 patients (8%) were positive
      for C. difficile and toxin genes. The HOHA-CDI incidence rate was 14.1 cases per
      10,000 patient days (95% CI: 10.5-18.6). Six patients with HOHA CDI died. ST54 (n
      = 14, 20%) was the most common type of HOHA-CDI strain circulating in the
      hospital during the study period and was linked to a temporal cluster (outbreak)
      involving two (NICU and GICU) of the four ICUs. Conclusion: HOHA-CDI occurs among
      ICU patients at this teaching hospital, supporting the importance of routine
      testing for CDI. Information on strain distribution can help detect CDI
      outbreaks. Detection of ST54 strain in a temporal cluster suggests possible gaps
      in infection control practices that should be investigated and addressed as
      needed.

PMID- 29636740
TI  - Stair-Step Pattern of Soil Bacterial Diversity Mainly Driven by pH and Vegetation
      Types Along the Elevational Gradients of Gongga Mountain, China.
AB  - Ecological understandings of soil bacterial community succession and assembly
      mechanism along elevational gradients in mountains remain not well understood.
      Here, by employing the high-throughput sequencing technique, we systematically
      examined soil bacterial diversity patterns, the driving factors, and community
      assembly mechanisms along the elevational gradients of 1800-4100 m on Gongga
      Mountain in China. Soil bacterial diversity showed an extraordinary stair-step
      pattern along the elevational gradients. There was an abrupt decrease of
      bacterial diversity between 2600 and 2800 m, while no significant change at
      either lower (1800-2600 m) or higher (2800-4100 m) elevations, which coincided
      with the variation in soil pH. In addition, the community structure differed
      significantly between the lower and higher elevations, which could be primarily
      attributed to shifts in soil pH and vegetation types. Although there was no
      direct effect of MAP and MAT on bacterial community structure, our partial least
      squares path modeling analysis indicated that bacterial communities were
      indirectly influenced by climate via the effect on vegetation and the derived
      effect on soil properties. As for bacterial community assembly mechanisms, the
      null model analysis suggested that environmental filtering played an overwhelming
      role in the assembly of bacterial communities in this region. In addition,
      variation partition analysis indicated that, at lower elevations, environmental
      attributes explained much larger fraction of the beta-deviation than spatial
      attributes, while spatial attributes increased their contributions at higher
      elevations. Our results highlight the importance of environmental filtering, as
      well as elevation-related spatial attributes in structuring soil bacterial
      communities in mountain ecosystems.

PMID- 29636741
TI  - Differential Activity of the Combination of Vancomycin and Amikacin on Planktonic
      vs. Biofilm-Growing Staphylococcus aureus Bacteria in a Hollow Fiber Infection
      Model.
AB  - Combining currently available antibiotics to optimize their use is a promising
      strategy to reduce treatment failures against biofilm-associated infections.
      Nevertheless, most assays of such combinations have been performed in vitro on
      planktonic bacteria exposed to constant concentrations of antibiotics over only
      24 h and the synergistic effects obtained under these conditions do not
      necessarily predict the behavior of chronic clinical infections associated with
      biofilms. To improve the predictivity of in vitro combination assays for
      bacterial biofilms, we first adapted a previously described Hollow-fiber (HF)
      infection model by allowing a Staphylococcus aureus biofilm to form before drug
      exposure. We then mimicked different concentration profiles of amikacin and
      vancomycin, similar to the free plasma concentration profiles that would be
      observed in patients treated daily over 5 days. We assessed the ability of the
      two drugs, alone or in combination, to reduce planktonic and biofilm-embedded
      bacterial populations, and to prevent the selection of resistance within these
      populations. Although neither amikacin nor vancomycin exhibited any bactericidal
      activity on S. aureus in monotherapy, the combination had a synergistic effect
      and significantly reduced the planktonic bacterial population by -3.0 to -6.0
      log10 CFU/mL. In parallel, no obvious advantage of the combination, as compared
      to amikacin alone, was demonstrated on biofilm-embedded bacteria for which the
      addition of vancomycin to amikacin only conferred a further maximum reduction of
      0.3 log10 CFU/mL. No resistance to vancomycin was ever found whereas a few
      bacteria less-susceptible to amikacin were systematically detected before
      treatment. These resistant bacteria, which were rapidly amplified by exposure to
      amikacin alone, could be maintained at a low level in the biofilm population and
      even suppressed in the planktonic population by adding vancomycin. In conclusion,
      by adapting the HF model, we were able to demonstrate the different bactericidal
      activities of the vancomycin and amikacin combination on planktonic and biofilm
      embedded bacterial populations, suggesting that, for biofilm-associated
      infections, the efficacy of this combination would not be much greater than with
      amikacin monotherapy. However, adding vancomycin could reduce possible resistance
      to amikacin and provide a relevant strategy to prevent the selection of
      antibiotic-resistant bacteria during treatments.

PMID- 29636742
TI  - Rumen Biohydrogenation and Microbial Community Changes Upon Early Life
      Supplementation of 22:6n-3 Enriched Microalgae to Goats.
AB  - Dietary supplementation of docosahexaenoic acid (DHA)-enriched products inhibits
      the final step of biohydrogenation in the adult rumen, resulting in the
      accumulation of 18:1 isomers, particularly of trans(t)-11 18:1. Occasionally, a
      shift toward the formation of t10 intermediates at the expense of t11
      intermediates can be triggered. However, whether similar impact would occur when
      supplementing DHA-enriched products during pregnancy or early life remains
      unknown. Therefore, the current in vivo study aimed to investigate the effect of
      a nutritional intervention with DHA in the early life of goat kids on rumen
      biohydrogenation and microbial community. Delivery of DHA was achieved by
      supplementing DHA-enriched microalgae (DHA Gold) either to the maternal diet
      during pregnancy (prenatal) or to the diet of the young offspring (postnatal). At
      the age of 12 weeks, rumen fluid was sampled for analysis of long-chain fatty
      acids and microbial community based on bacterial 16S rRNA amplicon sequencing.
      Postnatal supplementation with DHA-enriched microalgae inhibited the final
      biohydrogenation step, as observed in adult animals. This resulted particularly
      in increased ruminal proportions of t11 18:1 rather than a shift to t10
      intermediates, suggesting that both young and adult goats might be less prone to
      dietary induced shifts toward the formation of t10 intermediates, in comparison
      with cows. Although Butyrivibrio species have been identified as the most
      important biohydrogenating bacteria, this genus was more abundant when complete
      biohydrogenation, i.e. 18:0 formation, was inhibited. Blautia abundance was
      positively correlated with 18:0 accumulation, whereas Lactobacillus spp.
      Dialister spp. and Bifidobacterium spp. were more abundant in situations with
      greater t10 accumulation. Extensive comparisons made between current results and
      literature data indicate that current associations between biohydrogenation
      intermediates and rumen bacteria in young goats align with former observations in
      adult ruminants.

PMID- 29636743
TI  - Alfalfa Intervention Alters Rumen Microbial Community Development in Hu Lambs
      During Early Life.
AB  - The pre-weaning period is crucial for rumen developmental plasticity, which can
      have a long-term impact on animal performance. Understanding the rumen microbiota
      during early life is important to elucidate its potential role in rumen
      development. In this study, the rumen microbiota of 10-day-old Hu lambs fed
      either milk replacer (B-10), milk replacer and starter (STA) or milk replacer and
      starter supplemented with alfalfa (S-ALF) in the pre- (d17, 24, and 38) and post
      weaning periods (d45 and 66) were assessed to characterize rumen microbial
      colonization during early life and its response to fiber intervention. In the
      rumens of B-10 lambs, 498 operational taxonomic units belonging to 33 predominant
      genera were observed, and the top six predicted functions included "Membrane
      transport," "carbohydrate metabolism," "amino acid metabolism," "replication and
      repair," "translation," and "energy metabolism." Prevotella, Succinivibrio,
      Bifidobacterium, and Butyrivibrio abundances were increased at d38 for both STA
      and S-ALF groups compared to the B-10 group, whereas fibrolytic bacteria of the
      taxa Lachnospiraceae and Treponema were only increased in the S-ALF group at d38.
      A number of saccharolytic bacteria (Bacteroidaceae), organic acid-producing
      bacteria (Coprococcus and Actinomyces), proteolytic and amino acid fermenters
      (Fusobacterium) and fibrolytic bacteria (unclassified Ruminococcaceae) were
      significantly decreased in the STA lambs but not in the S-ALF lambs at d38. After
      weaning and exposed to alfalfa, the rumen microbial composition in the STA group
      started to appear similar to that of the S-ALF lambs. The relative abundance of
      unclassified Clostridiales was higher in S-ALF lambs than STA lambs after
      weaning. Spearman's correlation analysis showed positive relationships between
      unclassified Lachnospiraceae, unclassified Clostridiales, Treponema, unclassified
      Bacteroidales, Coprococcus and crude protein intake, neutral detergent fiber
      intake, and plasma beta-hydroxybutyrate. The unclassified Lachnospiraceae and
      Treponema were also positively correlated with average daily gain. Our results
      revealed that alfalfa stimulated changes in rumen microbiota during the pre- and
      post-weaning periods and was consistent with rumen development for better feed
      intake and animal performance before and after weaning. The findings of this
      study provide clues for strategies to improve rumen function through manipulation
      of the rumen microbiota during early life.

PMID- 29636745
TI  - Benthic Algal Community Structures and Their Response to Geographic Distance and
      Environmental Variables in the Qinghai-Tibetan Lakes With Different Salinity.
AB  - Uncovering the limiting factors for benthic algal distributions in lakes is of
      great importance to understanding of their role in global carbon cycling.
      However, limited is known about the benthic algal community distribution and how
      they are influenced by geographic distance and environmental variables in alpine
      lakes. Here, we investigated the benthic algal community compositions in the
      surface sediments of six lakes on the Qinghai-Tibetan Plateau (QTP), China
      (salinity ranging from 0.8 to 365.6 g/L; pairwise geographic distance among the
      studied lakes ranging 8-514 km) employing an integrated approach including
      Illumina-Miseq sequencing and environmental geochemistry. The results showed that
      the algal communities of the studied samples were mainly composed of orders of
      Bacillariales, Ceramiales, Naviculales, Oscillatoriales, Spirulinales,
      Synechococcales, and Vaucheriales. The benthic algal community compositions in
      these QTP lakes were significantly (p < 0.05) correlated with many environmental
      (e.g., dissolved inorganic and organic carbon, illumination intensity, total
      nitrogen and phosphorus, turbidity and water temperature) and spatial factors,
      and salinity did not show significant influence on the benthic algal community
      structures in the studied lakes. Furthermore, geographic distance showed strong,
      significant correlation (r = 0.578, p < 0.001) with the benthic algal community
      compositions among the studied lakes, suggesting that spatial factors may play
      important roles in influencing the benthic algal distribution. These results
      expand our current knowledge on the influencing factors for the distributions of
      benthic alga in alpine lakes.

PMID- 29636744
TI  - Pan-Genome Analysis Links the Hereditary Variation of Leptospirillum ferriphilum
      With Its Evolutionary Adaptation.
AB  - Niche adaptation has long been recognized to drive intra-species differentiation
      and speciation, yet knowledge about its relatedness with hereditary variation of
      microbial genomes is relatively limited. Using Leptospirillum ferriphilum species
      as a case study, we present a detailed analysis of genomic features of five
      recognized strains. Genome-to-genome distance calculation preliminarily
      determined the roles of spatial distance and environmental heterogeneity that
      potentially contribute to intra-species variation within L. ferriphilum species
      at the genome level. Mathematical models were further constructed to extrapolate
      the expansion of L. ferriphilum genomes (an 'open' pan-genome), indicating the
      emergence of novel genes with new sequenced genomes. The identification of
      diverse mobile genetic elements (MGEs) (such as transposases, integrases, and
      phage-associated genes) revealed the prevalence of horizontal gene transfer
      events, which is an important evolutionary mechanism that provides avenues for
      the recruitment of novel functionalities and further for the genetic divergence
      of microbial genomes. Comprehensive analysis also demonstrated that the genome
      reduction by gene loss in a broad sense might contribute to the observed
      diversification. We thus inferred a plausible explanation to address this
      observation: the community-dependent adaptation that potentially economizes the
      limiting resources of the entire community. Now that the introduction of new
      genes is accompanied by a parallel abandonment of some other ones, our results
      provide snapshots on the biological fitness cost of environmental adaptation
      within the L. ferriphilum genomes. In short, our genome-wide analyses bridge the
      relation between genetic variation of L. ferriphilum with its evolutionary
      adaptation.

PMID- 29636746
TI  - Typical Soil Redox Processes in Pentachlorophenol Polluted Soil Following Biochar
      Addition.
AB  - Reductive dechlorination is the primary pathway for environmental removal of
      pentachlorophenol (PCP) in soil under anaerobic condition. This process has been
      verified to be coupled with other soil redox processes of typical biogenic
      elements such as carbon, iron and sulfur. Meanwhile, biochar has received
      increasing interest in its potential for remediation of contaminated soil, with
      the effect seldom investigated under anaerobic environment. In this study, a 120
      day anaerobic incubation experiment was conducted to investigate the effects of
      biochar on soil redox processes and thereby the reductive dechlorination of PCP
      under anaerobic condition. Biochar addition (1%, w/w) enhanced the dissimilatory
      iron reduction and sulfate reduction while simultaneously decreased the PCP
      reduction significantly. Instead, the production of methane was not affected by
      biochar. Interestingly, however, PCP reduction was promoted by biochar when
      microbial sulfate reduction was suppressed by addition of typical inhibitor
      molybdate. Together with Illumina sequencing data regarding analysis of soil
      bacteria and archaea responses, our results suggest that under anaerobic
      condition, the main competition mechanisms of these typical soil redox processes
      on the reductive dechlorination of PCP may be different in the presence of
      biochar. In particularly, the effect of biochar on sulfate reduction process is
      mainly through promoting the growth of sulfate reducer (Desulfobulbaceae and
      Desulfobacteraceae) but not as an electron shuttle. With the supplementary
      addition of molybdate, biochar application is suggested as an improved strategy
      for a better remediation results by coordinating the interaction between
      dechlorination and its coupled soil redox processes, with minimum production of
      toxic sulfur reducing substances and relatively small emission of greenhouse gas
      (CH4) while maximum removal of PCP.

PMID- 29636747
TI  - Glucose and Applied Voltage Accelerated p-Nitrophenol Reduction in Biocathode of
      Bioelectrochemical Systems.
AB  - p-Nitrophenol (PNP) is common in the wastewater from many chemical industries. In
      this study, we investigated the effect of initial concentrations of PNP and
      glucose and applied voltage on PNP reduction in biocathode BESs and open-circuit
      biocathode BESs (OC-BES). The PNP degradation efficiency of a biocathode BES with
      0.5 V (Bioc-0.5) reached 99.5 +/- 0.8%, which was higher than the degradation
      efficiency of the BES with 0 V (Bioc-0) (62.4 +/- 4.5%) and the OC-BES (59.2 +/-
      12.5%). The PNP degradation rate constant (kPNP) of Bioc-0.5 was 0.13 +/- 0.01 h
      1, which was higher than the kPNP of Bioc-0 (0.024 +/- 0.002 h-1) and OC-BES
      (0.013 +/- 0.0005 h-1). PNP degradation depended on the initial concentrations of
      glucose and PNP. A glucose concentration of 0.5 g L-1 was best for PNP
      degradation. The initial PNP increased from 50 to 130 mg L-1 and the kPNP
      decreased from 0.093 +/- 0.008 to 0.027 +/- 0.001 h-1. High-throughput sequencing
      of 16S rRNA gene amplicons indicated differences in microbial community structure
      between BESs with different voltages and the OC-BES. The predominant populations
      were affiliated with Streptococcus (42.7%) and Citrobacter (54.1%) in biocathode
      biofilms of BESs, and Dysgonomonas were the predominant microorganisms in
      biocathode biofilms of OC-BESs. The predominant populations were different among
      the cathode biofilms and the suspensions. These results demonstrated that applied
      voltage and biocathode biofilms play important roles in PNP degradation.

PMID- 29636748
TI  - Various Profiles of tet Genes Addition to tet(X) in Riemerella anatipestifer
      Isolates From Ducks in China.
AB  - To investigate tetracycline resistance and resistant genotype in Riemerella
      anatipestifer, the tetracycline susceptibility of 212 R. anatipestifer isolates
      from China between 2011 and 2017 was tested. The results showed that 192 of 212
      (90.6%) R. anatipestifer isolates exhibited resistance to tetracycline (the MICs
      ranged from 4 to 256 MUg/ml). The results of PCR detection showed that, 170 of
      212 (80.2%) R. anatipestifer isolates possessed the tet(X) gene. Other genes,
      including tet(A), tet(M), tet(Q), tet(O), tet(B), and tet(O/W/32/O), were found
      at frequencies of 20.8, 4.7, 1.4, 0.9, 0.9, and 0.5%, respectively. However,
      tet(C), tet(E), tet(G), tet(K), and tet(W) were not detected in any isolate. In
      these tet gene positive strains, 31 (14.6%), 2 (0.9%), 5 (2.4%), 1 (0.5%), 3
      (1.4%) were detected containing tet(A)/tet(X), tet(M)/tet(O), tet(M)/tet(X),
      tet(O)/tet(X), and tet(Q)/tet(X) simultaneously, respectively. One isolates,
      R131, unexpectedly contained three tet genes, i.e., tet(M), tet(O), and tet(X).
      Sequence analysis of the tet gene ORFs cloned from R. anatipestifer isolates
      confirmed that tet(A), tet(B), tet(M), tet(O), tet(Q) and an unusual mosaic tet
      gene tet(O/W/32/O) were present in R. anatipestifer. The MIC results of R.
      anatipestifer ATCC 11845 transconjugants carrying tet(A), tet(B), tet(M), tet(O),
      tet(O/W/32/O), tet(Q), and tet(X) genes exhibited tetracycline resistance with
      MIC values ranging from 4 to 64 MUg/ml. Additionally, the tet(X) gene could
      transfer into susceptible strain via natural transformation (transformation
      frequencies of ~10-6). In conclusion, the tet(A), tet(B), tet(M), tet(O),
      tet(O/W/32/O), tet(Q), and tet(X) genes were found and conferred tetracycline
      resistance in R. anatipestifer isolates. Moreover, the tet(X) is the main
      mechanism of tetracycline resistance in R. anatipestifer isolates. To our
      knowledge, this is the first report of tet(A), tet(B), tet(M), tet(O), tet(Q),
      and mosaic gene tet(O/W/32/O) in R. anatipestifer.

PMID- 29636749
TI  - Prediction of Phenotypic Antimicrobial Resistance Profiles From Whole Genome
      Sequences of Non-typhoidal Salmonella enterica.
AB  - Surveillance of antimicrobial resistance (AMR) in non-typhoidal Salmonella
      enterica (NTS), is essential for monitoring transmission of resistance from the
      food chain to humans, and for establishing effective treatment protocols. We
      evaluated the prediction of phenotypic resistance in NTS from genotypic profiles
      derived from whole genome sequencing (WGS). Genes and chromosomal mutations
      responsible for phenotypic resistance were sought in WGS data from 3,491 NTS
      isolates received by Public Health England's Gastrointestinal Bacteria Reference
      Unit between April 2014 and March 2015. Inferred genotypic AMR profiles were
      compared with phenotypic susceptibilities determined for fifteen antimicrobials
      using EUCAST guidelines. Discrepancies between phenotypic and genotypic profiles
      for one or more antimicrobials were detected for 76 isolates (2.18%) although
      only 88/52,365 (0.17%) isolate/antimicrobial combinations were discordant. Of the
      discrepant results, the largest number were associated with streptomycin (67.05%,
      n = 59). Pan-susceptibility was observed in 2,190 isolates (62.73%). Overall,
      resistance to tetracyclines was most common (26.27% of isolates, n = 917)
      followed by sulphonamides (23.72%, n = 828) and ampicillin (21.43%, n = 748).
      Multidrug resistance (MDR), i.e., resistance to three or more antimicrobial
      classes, was detected in 848 isolates (24.29%) with resistance to ampicillin,
      streptomycin, sulphonamides and tetracyclines being the most common MDR profile
      (n = 231; 27.24%). For isolates with this profile, all but one were S.
      Typhimurium and 94.81% (n = 219) had the resistance determinants blaTEM-1,strA
      strB, sul2 and tet(A). Extended-spectrum beta-lactamase genes were identified in
      41 isolates (1.17%) and multiple mutations in chromosomal genes associated with
      ciprofloxacin resistance in 82 isolates (2.35%). This study showed that WGS is
      suitable as a rapid means of determining AMR patterns of NTS for public health
      surveillance.

PMID- 29636750
TI  - The Small Regulatory RNAs LhrC1-5 Contribute to the Response of Listeria
      monocytogenes to Heme Toxicity.
AB  - The LhrC family of small regulatory RNAs (sRNAs) is known to be induced when the
      foodborne pathogen Listeria monocytogenes is exposed to infection-relevant
      conditions, such as human blood. Here we demonstrate that excess heme, the core
      component of hemoglobin in blood, leads to a strong induction of the LhrC family
      members LhrC1-5. The heme-dependent activation of lhrC1-5 relies on the response
      regulator LisR, which is known to play a role in virulence and stress tolerance.
      Importantly, our studies revealed that LhrC1-5 and LisR contribute to the
      adaptation of L. monocytogenes to excess heme. Regarding the regulatory function
      of the sRNAs, we demonstrate that LhrC1-5 act to down-regulate the expression of
      known LhrC target genes under heme-rich conditions: oppA, tcsA, and lapB,
      encoding surface exposed proteins with virulence functions. These genes were
      originally identified as targets for LhrC-mediated control under cell envelope
      stress conditions, suggesting a link between the response to heme toxicity and
      cell envelope stress in L. monocytogenes. We also investigated the role of LhrC1
      5 in controlling the expression of genes involved in heme uptake and utilization:
      lmo2186 and lmo2185, encoding the heme-binding proteins Hbp1 and Hbp2,
      respectively, and lmo0484, encoding a heme oxygenase-like protein. Using in vitro
      binding assays, we demonstrated that the LhrC family member LhrC4 interacts with
      mRNAs encoded from lmo2186, lmo2185, and lmo0484. For lmo0484, we furthermore
      show that LhrC4 uses a CU-rich loop for basepairing to the AG-rich Shine-Dalgarno
      region of the mRNA. The presence of a link between the response to heme toxicity
      and cell envelope stress was further underlined by the observation that LhrC1-5
      down-regulate the expression of lmo0484 in response to the cell wall-acting
      antibiotic cefuroxime. Collectively, this study suggests a role for the LisR
      regulated sRNAs LhrC1-5 in a coordinated response to excess heme and cell
      envelope stress in L. monocytogenes.

PMID- 29636751
TI  - Hydrogen Sulfide Reduces Myeloid-Derived Suppressor Cell-Mediated Inflammatory
      Response in a Model of Helicobacter hepaticus-Induced Colitis.
AB  - Chronic inflammation contributes to tumor initiation in colitis-associated
      colorectal cancer (CRC). Indeed, inflammatory bowel disease (IBD) patients show
      an increased risk of developing CRC. Cancer immune evasion is a major issue in
      CRC and preclinical and clinical evidence has defined a critical role for myeloid
      derived suppressor cells (MDSCs) that contribute to tumor growth and progression
      by suppressing T-cells and modulating innate immune responses. MDSCs comprise a
      heterogeneous population of immature myeloid cells that can be distinct in two
      subtypes: CD11b+Ly6G+Ly6Clow with granulocytic phenotype (G-MDSCs) and CD11b+Ly6G
      Ly6Chigh with monocytic phenotype (M-MDSCs). Hydrogen sulfide (H2S) is an
      endogenous gaseous signaling molecule that regulates various physiological and
      pathophysiological functions. In particular, several studies support its anti
      inflammatory activity in experimental colitis and ulcer. However, the role of the
      H2S pathway in innate immune-mediated IBD has not yet been elucidated. To better
      define a possible link between MDSCs and H2S pathway in colitis-associated CRC
      development, we used an innate immune-mediated IBD model induced by infection
      with the bacterium Helicobacter hepaticus (Hh), closely resembling human IBD.
      Here, we demonstrated an involvement of MDSCs in colitis development. A
      significant time-dependent increase of both G-MDSCs and M-MDSCs was observed in
      the colon and in the spleen of Hh-infected mice. Following, we observed that
      chronic oral administration of the H2S donor DATS reduced colon inflammation by
      limiting the recruitment of G-MDSCs in the colon of Hh-infected mice. Thus, we
      identify the metabolic pathway l-cysteine/H2S as a possible new player in the
      immunosuppressive mechanism responsible for the MDSCs-promoted colitis-associated
      cancer development.

PMID- 29636752
TI  - Autoantibodies in Autoimmune Liver Disease-Clinical and Diagnostic Relevance.
AB  - Testing for liver-related autoantibodies should be included in the workup of
      patients with hepatitis or cholestasis of unknown origin. Although most of these
      autoantibodies are not disease specific, their determination is a prerequisite to
      diagnose autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC), and
      they are components of the diagnostic scoring system in these diseases. In
      primary sclerosing cholangitis (PSC), on the other hand, autoantibodies are
      frequently present but play a minor role in establishing the diagnosis. In PSC,
      however, data on antibodies suggest a link between disease pathogenesis and the
      intestinal microbiota. This review will focus on practical aspects of antibody
      testing in the three major autoimmune liver diseases AIH, PBC, and PSC.

PMID- 29636753
TI  - Elevated Level of CD4+ T Cell Immune Activation in Acutely HIV-1-Infected Stage
      Associates With Increased IL-2 Production and Cycling Expression, and Subsequent
      CD4+ T Cell Preservation.
AB  - Persistent immune activation is a striking consequence of HIV-1 infection and a
      driving force of CD4+ T cell depletion and AIDS events during chronic infection.
      High level of T cell immune activation associates with antiretroviral therapy
      (ART)-treated clinical outcomes in chronically HIV-1-infected patients. However,
      the role of T cell activation during acute infection stage in subsequent CD4+ T
      cell decline in the absence of ART treatment is unknown. In this study, we
      enrolled 26 acutely HIV-1-infected patients in the absence of ART treatment from
      a prospective acute HIV-1 infection cohort in Beijing (PRIMO). A comprehensive
      analysis of CD4+ and CD8+ T cell immune activation during acute infection stage
      and the clinical outcomes was studied. We found that patients with higher level
      of CD4+ T cell activation (%CD38+HLA-DR+CD4+ T cells) exhibited more effective
      function (%IL-2 production and %ki67 expression) in CD4+ T cells compared to
      those from patients without increased T cell activation at the acute phase.
      Direct correlations were observed between CD4+ T cell activation and the
      percentages of IL-2-producing or ki67-expressing CD4+ T cells in patients at the
      acute phase of infection. Importantly, the increased levels of CD4+ T cell immune
      activation, IL-2 production, and cycling expression during acute infection were
      associated with less decline of CD4+ T cell after 2 years of infection. However,
      immune exhaustion molecules in acute infection, including CD160, T cell
      immunoglobulin and ITIM domain, programmed cell death protein 1, and T cell
      immunoglobulin and mucin 3, were not associated with the CD4+ T cell depletion.
      These significant associations of CD4+ T cell activation were not demonstrable
      for CD8+ T cell activation at the acute phase. Taken together, our observations
      provide new insight into the possible role of T cell activation in preventing
      CD4+ T cell depletion during acute HIV-1 infection.

PMID- 29636754
TI  - Macrophage Transactivation for Chemokine Production Identified as a Negative
      Regulator of Granulomatous Inflammation Using Agent-Based Modeling.
AB  - Cellular activation in trans by interferons, cytokines, and chemokines is a
      commonly recognized mechanism to amplify immune effector function and limit
      pathogen spread. However, an optimal host response also requires that collateral
      damage associated with inflammation is limited. This may be particularly so in
      the case of granulomatous inflammation, where an excessive number and/or
      excessively florid granulomas can have significant pathological consequences.
      Here, we have combined transcriptomics, agent-based modeling, and in vivo
      experimental approaches to study constraints on hepatic granuloma formation in a
      murine model of experimental leishmaniasis. We demonstrate that chemokine
      production by non-infected Kupffer cells in the Leishmania donovani-infected
      liver promotes competition with infected KCs for available iNKT cells, ultimately
      inhibiting the extent of granulomatous inflammation. We propose trans-activation
      for chemokine production as a novel broadly applicable mechanism that may operate
      early in infection to limit excessive focal inflammation.

PMID- 29636755
TI  - Development of a Live Recombinant BCG Expressing Human Immunodeficiency Virus
      Type 1 (HIV-1) Gag Using a pMyong2 Vector System: Potential Use As a Novel HIV-1
      Vaccine.
AB  - Even though the rate of new human immunodeficiency virus type 1 (HIV-1)
      infections is gradually decreasing worldwide, an effective preventive vaccine for
      HIV-1 is still urgently needed. The recombinant Mycobacterium bovis BCG (rBCG) is
      promising for the development of an HIV-1 vaccine. Recently, we showed that a
      recombinant Mycobacterium smegmatis expressing HIV-1 gag in a pMyong2 vector
      system (rSmeg-pMyong2-p24) increased the efficacy of a vaccine against HIV-1 in
      mice. Here, we evaluated the potential of an rBCG expressing HIV-1 p24 antigen
      Gag in pMyong2 (rBCG-pMyong2-p24) in a vaccine application for HIV-1 infection.
      We found that rBCG-pMyong2-p24 elicited an enhanced HIV-1 p24 Gag expression in
      rBCG and infected antigen-presenting cells. We also found that compared to rBCG
      pAL-p24 in a pAL5000 derived vector system, rBCG-pMyong2-p24 elicited enhanced
      p24-specific immune responses in vaccinated mice as evidenced by higher levels of
      HIV-1 Gag-specific CD4 and CD8 T lymphocyte proliferation, gamma interferon
      ELISPOT cell induction, antibody production, and cytotoxic T lymphocytes (CTL)
      responses. Furthermore, rBCG-pMyong2-p24 showed a higher level of p24-specific Ab
      production than rSmeg-pMyong2-p24 in the same pMyong2 vector system. In
      conclusion, our data indicated that a live recombinant BCG expressing HIV-1 Gag
      using a pMyong2 vector system, rBCG-pMyong2-p24 elicited an enhanced immune
      response against HIV-1 infections in a mouse model system. So, rBCG-pMyong2-p24
      may have the potential as a prime vaccine in a heterologous prime-boost vaccine
      strategy for HIV-1 infection.

PMID- 29636756
TI  - Interactive Effects of Elevated CO2 and N Fertilization on Yield and Quality of
      Tomato Grown Under Reduced Irrigation Regimes.
AB  - The interactive effects of CO2 elevation, N fertilization, and reduced irrigation
      regimes on fruit yield (FY) and quality in tomato (Solanum lycopersicum L.) were
      investigated in a split-root pot experiment. The plants were grown in two
      separate climate-controlled greenhouse cells at atmospheric [CO2] of 400 and 800
      ppm, respectively. In each cell, the plants were fertilized at either 100 or 200
      mg N kg-1 soil and were either irrigated to full water holding capacity [i.e., a
      volumetric soil water content of 18%; full irrigation (FI)], or using 70% water
      of FI to the whole pot [deficit irrigation (DI)] or alternately to only half of
      the pot [partial root-zone irrigation (PRI)]. The yield and fruit quality
      attributes mainly from sugars (sucrose, fructose, and glucose) and organic acids
      (OAs; citric acid and malic acid) to various ionic (NH4+, K+, Mg2+, Ca2+, NO3-,
      SO42-, and PO43-) concentrations in fruit juice were determined. The results
      indicated that lower N supply reduced fruit number and yield, whereas it enhanced
      some of the quality attributes of fruit as indicated by greater firmness and
      higher concentrations of sugars and OAs. Elevated [CO2] (e[CO2]) attenuated the
      negative influence of reduced irrigation (DI and PRI) on FY. Principal component
      analysis revealed that the reduced irrigation regimes, especially PRI, in
      combination with e[CO2] could synergistically improve the comprehensive quality
      of tomato fruits at high N supply. These findings provide useful knowledge for
      sustaining tomato FY and quality in a future drier and CO2-enriched environment.

PMID- 29636757
TI  - The Nicotianamine Synthase Gene Is a Useful Candidate for Improving the
      Nutritional Qualities and Fe-Deficiency Tolerance of Various Crops.
AB  - With the global population predicted to grow by at least 25% by the year 2050,
      the sustainable production of nutritious foods will be necessary for human health
      and the environment. Iron (Fe) is an essential nutrient for both plants and
      humans. Fe is poorly soluble, especially at high pH levels, at which it is
      difficult for living organisms to accumulate sufficient Fe. In plants, Fe
      deficiency leads to low yield and poor nutritional quality, as it significantly
      affects chlorophyll synthesis. Fe deficiency is a worldwide agricultural problem
      that is especially serious in soils with a high pH, such as calcareous soils,
      which comprise approximately 30% of cultivated soils worldwide. Genetic
      improvements in crops that can tolerate Fe deficiency will be required to meet
      the demands for crop production and could ultimately contribute to the
      amelioration of global warming. Nicotianamine (NA) is an Fe chelator in plants
      that is involved in metal translocation in the plant body. In mammals, NA
      inhibits angiotensin I-converting enzyme, which plays a key role in blood
      pressure control. It was recently shown that the enhancement of NA production
      using nicotianamine synthase is useful for increasing not only NA but also Fe and
      Zn levels in crops such as rice, soybean, and sweet potato. Additionally, these
      plants showed Fe-deficiency tolerance in calcareous soil. These results suggested
      that NAS overexpression simultaneously improves food quality and increases plant
      production. This review summarizes progress in generating crops overexpressing
      NAS.

PMID- 29636758
TI  - Selection and Clonal Propagation of High Artemisinin Genotypes of Artemisia
      annua.
AB  - Artemisinin, produced in the glandular trichomes of Artemisia annua L. is a vital
      antimalarial drug effective against Plasmodium falciparum resistant to quinine
      derived medicines. Although work has progressed on the semi-synthetic production
      of artemisinin, field production of A. annua remains the principal commercial
      source of the compound. Crop production of artemisia must be increased to meet
      the growing worldwide demand for artemisinin combination therapies (ACTs) to
      treat malaria. Grower artemisinin yields rely on plants generated from seeds from
      open-pollinated parents. Although selection has considerably increased plant
      artemisinin concentration in the past 15 years, seed-generated plants have highly
      variable artemisinin content that lowers artemisinin yield per hectare. Breeding
      efforts to produce improved F1 hybrids have been hampered by the inability to
      produce inbred lines due to self-incompatibility. An approach combining
      conventional hybridization and selection with clonal propagation of superior
      genotypes is proposed as a means to enhance crop yield and artemisinin
      production. Typical seed-propagated artemisia plants produce less than 1% (dry
      weight) artemisinin with yields below 25 kg/ha. Genotypes were identified
      producing high artemisinin levels of over 2% and possessing improved agronomic
      characteristics such as high leaf area and shoot biomass production. Field
      studies of clonally-propagated high-artemisinin plants verified enhanced plant
      uniformity and an estimated gross primary productivity of up to 70 kg/ha
      artemisinin, with a crop density of one plant m-2. Tissue culture and cutting
      protocols for the mass clonal propagation of A. annua were developed for shoot
      regeneration, rooting, acclimatization, and field cultivation. Proof of concept
      studies showed that both tissue culture-regenerated plants and rooted cutting
      performed better than plants derived from seed in terms of uniformity, yield, and
      consistently high artemisinin content. Use of this technology to produce plants
      with homogeneously-high artemisinin can help farmers markedly increase the
      artemisinin yield per cultivated area. This would lead to increased profit to
      farmers and decreased prices of ACT.

PMID- 29636759
TI  - Alterations of Membrane Lipid Content Correlated With Chloroplast and
      Mitochondria Development in Euglena gracilis.
AB  - Euglenoids are unique protists that can grow photoautotrophically,
      photomixotrophically, and heterotrophically. Here we grew Euglena gracilis under
      these different growth conditions and determined cellular contents of seven
      membrane lipids and one storage lipid (triacylglycerol), which account for more
      than 94 mol% of total membrane lipids. We also describe the relationship among
      chloroplast and mitochondria developments with lipid contents, protein contents,
      and oxygen evolution/consumption rates. In photoautotrophic growth conditions, E.
      gracilis cells accumulated chlorophyll, photosynthetic proteins, and glycolipids
      typical to thylakoid membranes. The same occurred for the cells grown under
      photomixotrophic conditions with higher respiration rates. In heterotrophic
      conditions, E. gracilis cells had higher respiration rates compared to cells
      grown in other conditions with the accumulation of pyruvate: NADP+
      oxidoreductase, a mitochondrial protein and phospholipid common in mitochondria.
      Cells were also observed using a confocal laser scanning microscope and found to
      show more chlorophyll autofluorescence when grown photoautotrophically and
      photomixotrophycally, and fluorescence of MitoTracker when grown
      photomixotrophically and heterotrophically. These results suggest that under
      illumination, E. gracilis develops functional thylakoid membranes with membrane
      lipids and proteins for photosynthesis. In the medium with glucose, the cells
      develop mitochondria with phospholipids and proteins for respiration. Possible
      application based on lipid analysis for the enhancement of wax ester or alkene
      synthesis is discussed.

PMID- 29636760
TI  - Faba Greens, Globe Artichoke's Offshoots, Crenate Broomrape and Summer Squash
      Greens: Unconventional Vegetables of Puglia (Southern Italy) With Good Quality
      Traits.
AB  - Globe artichoke (Cynara cardunculus L. subsp. [L.] scolymus Hayek), summer squash
      (Cucurbita pepo L.) and faba bean (Vicia faba L.) are widely cultivated for their
      immature inflorescences, fruits and seeds, respectively. Nevertheless, in some
      areas of Puglia (Southern Italy), other organs of these species are traditionally
      used as vegetables, instead of being considered as by-products. Offshoots (so
      called cardoni or carducci) of globe artichoke, produced during the vegetative
      growing cycle and removed by common cultural procedures, are used like to the
      cultivated cardoons (C. cardunculus L. var. altilis DC). The stems, petioles,
      flowers and smaller leaves of summer squash are used as greens (so-called cime di
      zucchini), like other leafy vegetables such as chicory (Cichorium intybus L.) and
      Swiss chard (Beta vulgaris L.). Also the plant apex of faba bean, about 5-10 cm
      long, obtained from the green pruning, are used as greens (so-called cime di
      fava) like spinach leaves. Moreover, crenate broomrape (Orobanche crenata
      Forssk.), a root parasite plant that produces devastating effects on many crops
      (mostly legumes), is used like asparagus (Asparagus officinalis L.) to prepare
      several traditional dishes. In this study ethnobotanical surveys and quality
      assessment of these unconventional vegetables were performed. For their content
      of fiber, offshoots of globe artichokes can be considered a useful food to bowel.
      Summer squash greens could be recommended as a vegetable to use especially in the
      case of hypoglycemic diets considering both content and composition of their
      carbohydrates. For their low content of nitrate, faba greens could be recommended
      as a substitute of nitrate-rich leafy vegetables. Crenate broomrape shows a high
      antioxidant activity and may be considered as a very nutritious agri-food
      product. Overall, the results of the present study indicate that offshoots of
      globe artichoke, summer squash greens, faba greens and crenate broomrape have
      good potential as novel foods, being nutritious and refined products. Their
      exploitation aiming to the obtainment of labeled and/or new potential ready-to
      eat retail products could satisfy the demand for local functional foods.

PMID- 29636761
TI  - Genome-Wide Association Study for Identification and Validation of Novel SNP
      Markers for Sr6 Stem Rust Resistance Gene in Bread Wheat.
AB  - : Stem rust (caused by Puccinia graminis f. sp. tritici Erikss. & E. Henn.), is a
      major disease in wheat (Triticum aestivium L.). However, in recent years it
      occurs rarely in Nebraska due to weather and the effective selection and gene
      pyramiding of resistance genes. To understand the genetic basis of stem rust
      resistance in Nebraska winter wheat, we applied genome-wide association study
      (GWAS) on a set of 270 winter wheat genotypes (A-set). Genotyping was carried out
      using genotyping-by-sequencing and ~35,000 high-quality SNPs were identified. The
      tested genotypes were evaluated for their resistance to the common stem rust race
      in Nebraska (QFCSC) in two replications. Marker-trait association identified 32
      SNP markers, which were significantly (Bonferroni corrected P < 0.05) associated
      with the resistance on chromosome 2D. The chromosomal location of the significant
      SNPs (chromosome 2D) matched the location of Sr6 gene which was expected in these
      genotypes based on pedigree information. A highly significant linkage
      disequilibrium (LD, r2 ) was found between the significant SNPs and the specific
      SSR marker for the Sr6 gene (Xcfd43). This suggests the significant SNP markers
      are tagging Sr6 gene. Out of the 32 significant SNPs, eight SNPs were in six
      genes that are annotated as being linked to disease resistance in the IWGSC
      RefSeq v1.0. The 32 significant SNP markers were located in nine haplotype
      blocks. All the 32 significant SNPs were validated in a set of 60 different
      genotypes (V-set) using single marker analysis. SNP markers identified in this
      study can be used in marker-assisted selection, genomic selection, and to develop
      KASP (Kompetitive Allele Specific PCR) marker for the Sr6 gene. Highlights: Novel
      SNPs for Sr6 gene, an important stem rust resistant gene, were identified and
      validated in this study. These SNPs can be used to improve stem rust resistance
      in wheat.

PMID- 29636762
TI  - A Transcriptomic Analysis of Xylan Mutants Does Not Support the Existence of a
      Secondary Cell Wall Integrity System in Arabidopsis.
AB  - Yeast have long been known to possess a cell wall integrity (CWI) system, and
      recently an analogous system has been described for the primary walls of plants
      (PCWI) that leads to changes in plant growth and cell wall composition. A similar
      system has been proposed to exist for secondary cell walls (SCWI). However, there
      is little data to support this. Here, we analyzed the stem transcriptome of a set
      of cell wall biosynthetic mutants in order to investigate whether cell wall
      damage, in this case caused by aberrant xylan synthesis, activates a signaling
      cascade or changes in cell wall synthesis gene expression. Our data revealed
      remarkably few changes to the transcriptome. We hypothesize that this is because
      cells undergoing secondary cell wall thickening have entered a committed
      programme leading to cell death, and therefore a SCWI system would have limited
      impact. The absence of transcriptomic responses to secondary cell wall
      alterations may facilitate engineering of the secondary cell wall of plants.

PMID- 29636763
TI  - Functional and Taxonomic Differentiation of Macrophyte Assemblages Across the
      Yangtze River Floodplain Under Human Impacts.
AB  - Human activities and the consequent extirpations of species have been changing
      the composition of species assemblages worldwide. These anthropogenic impacts
      alter not only the richness of assemblages but also the biological dissimilarity
      among them. One of the main gaps in the assessment of biodiversity change in
      freshwater ecosystems is our limited understanding regarding how taxonomic and
      functional facets of macrophyte assemblages respond to human impacts on regional
      scales. Here, we assess the temporal (before 1970s against after 2000s) changes
      in taxonomic and functional richness and compositional dissimilarities,
      partitioned into its turnover and nestedness components, of freshwater macrophyte
      assemblages across the floodplain lakes of the Yangtze River in China. We found
      that functional and taxonomic assemblage differentiation occurred simultaneously
      under increasing human impact, concomitant to a general decrease in functional
      and taxonomic richness. However, this effect weakened when the historical level
      of taxonomic dissimilarity among assemblages was high. Macrophyte species with
      large dispersal range and submersed life form were significantly more susceptible
      to extirpation. The impact of human activities on differentiation was complex but
      habitat loss and fishery intensity were consistently the main drivers of
      assemblage change in these lakes, whereas water quality (i.e., light pollution
      and nutrient enrichment) had weaker effects. Further, macrophyte taxonomic and
      functional differentiation was mainly driven by the nestedness component of
      dissimilarity, accounting for changes in assemblage composition related to
      changes in species richness independent of species replacement. This result,
      markedly different from previous studies on freshwater fish assemblages conducted
      in these lakes, represents a novel contribution toward achieving a more holistic
      understanding of how human impacts contribute to shape community assemblages in
      natural ecosystems.

PMID- 29636764
TI  - Modeling Biometric Traits, Yield and Nutritional and Antioxidant Properties of
      Seeds of Three Soybean Cultivars Through the Application of Biostimulant
      Containing Seaweed and Amino Acids.
AB  - In recent years, attempts have been made to use preparations that allow obtaining
      high and good quality yields, while reducing the application of pesticides and
      mineral fertilizers. These include biostimulants that are safe for the natural
      environment and contribute to the improvement of yield size and quality,
      especially after the occurrence of stressors. Their use is advisable in the case
      of crops sensitive to such biotic stress factors like low temperatures or
      drought. One of these is soybean which is a very important plant from the
      economic viewpoint. Field experiments were established in the years 2014-2016 in
      a random block design in four replicates on experimental plots of 10 m2. Three
      soybean cultivars: Annushka, Mavka, and Atlanta were planted in the third decade
      of April. Fylloton biostimulant was used at 0.7% or 1% concentrations as single
      spraying (BBCH 13-15) or double spraying (BBCH 13-15, BBCH 61) in the vegetation
      period. The number of seeds per 1 m2, seed yield, thousand seed weight, number of
      pods per plant, number of nodes in the main shoot, height of plants, and protein
      and fat contents in seeds were determined. The content of phenolic compounds,
      antioxidant capacity and antioxidant effect of soybean seeds were assayed as
      well. Foliar treatment of soybean with Fylloton stimulated the growth and yield
      of plants without compromising their nutritional and nutraceutical properties.
      The double application of the higher concentration of Fylloton was favorable for
      the plant height, seed number and soybean yield. Moreover, the highest number of
      pods was obtained after single treatment of plants with the lower biostimulant
      concentration. There was also a positive effect of using this biostimulant on the
      content and activity of some bioactive compounds, such as phenolics and
      flavonoids, and on the reducing power.

PMID- 29636766
TI  - Phloem Girdling of Norway Spruce Alters Quantity and Quality of Wood Formation in
      Roots Particularly Under Drought.
AB  - Carbon (C) availability plays an essential role in tree growth and wood
      formation. We evaluated the hypothesis that a decrease in C availability (i)
      triggers mobilization of C reserves in the coarse roots of Picea abies to
      maintain growth and (ii) causes modification of wood structure notably under
      drought. The 6-year-old saplings were subjected to two levels of soil moisture
      (watered versus drought conditions) and root C status was manipulated by
      physically blocking phloem transport in the stem at three girdling dates (GDs).
      Stem girdling was done before the onset of bud break [day of the year (doy) 77],
      during vigorous aboveground shoot and radial stem growth (GD doy 138), and after
      cessation of shoot growth (GD doy 190). The effect of blockage of C transport on
      root growth, root phenology, and wood anatomical traits [cell lumen diameter
      (CLD) and cell wall thickness (CWT)] in earlywood (EW) and latewood (LW) was
      determined. To evaluate changes in belowground C status caused by girdling, non
      structural carbohydrates (soluble sugars and starch) in coarse roots were
      determined at the time of girdling and after the growing season. Although fine
      root mass significantly decreased in response to blockage of phloem C transport,
      the phenology of root elongation growth was not affected. Surprisingly, radial
      root growth and CLD of EW tracheids in coarse roots were strikingly increased in
      drought-stressed trees, when girdling occurred before bud break or during
      aboveground stem growth. In watered trees, the growth response to girdling was
      less distinct, but the CWT of EW significantly increased. Starch reserves in the
      roots of girdled trees significantly decreased in both soil moisture treatments
      and at all GDs. We conclude that (i) radial growth and wood development in coarse
      roots of P. abies saplings are not only dependent on current photosynthates, and
      (ii) blockage of phloem transport induces physiological changes that outweigh
      drought effects imposed on root cambial activity and cell differentiation.

PMID- 29636765
TI  - Soil Selenium (Se) Biofortification Changes the Physiological, Biochemical and
      Epigenetic Responses to Water Stress in Zea mays L. by Inducing a Higher Drought
      Tolerance.
AB  - Requiring water and minerals to grow and to develop its organs, Maize (Zea mays
      L.) production and distribution is highly rainfall-dependent. Current global
      climatic changes reveal irregular rainfall patterns and this could represent for
      maize a stressing condition resulting in yield and productivity loss around the
      world. It is well known that low water availability leads the plant to adopt a
      number of metabolic alterations to overcome stress or reduce its effects. In this
      regard, selenium (Se), a trace element, can help reduce water damage caused by
      the overproduction of reactive oxygen species (ROS). Here we report the effects
      of exogenous Se supply on physiological and biochemical processes that may
      influence yield and quality of maize under drought stress conditions. Plants were
      grown in soil fertilized by adding 150 mg of Se (sodium selenite). We verified
      the effects of drought stress and Se treatment. Selenium biofortification proved
      more beneficial for maize plants when supplied at higher Se concentrations. The
      increase in proline, K concentrations and nitrogen metabolism in aerial parts of
      plants grown in Se-rich substrates, seems to prove that Se-biofortification
      increased plant resistance to water shortage conditions. Moreover, the increase
      of SeMeSeCys and SeCys2 forms in roots and aerial parts of Se-treated plants
      suggest resistance strategies to Se similar to those existing in Se
      hyperaccumulator species. In addition, epigenetic changes in DNA methylation due
      to water stress and Se treatment were also investigated using methylation
      sensitive amplified polymorphism (MSAP). Results suggest that Se may be an
      activator of particular classes of genes that are involved in tolerance to
      abiotic stresses. In particular, PSY (phytoene synthase) gene, essential for
      maintaining leaf carotenoid contents, SDH (sorbitol dehydrogenase), whose
      activity regulates the level of important osmolytes during drought stress and ADH
      (alcohol dehydrogenase), whose activity plays a central role in biochemical
      adaptation to environmental stress. In conclusion, Se-biofortification could help
      maize plants to cope with drought stress conditions, by inducing a higher drought
      tolerance.

PMID- 29636767
TI  - High-Density Genetic Map Construction and Stem Total Polysaccharide Content
      Related QTL Exploration for Chinese Endemic Dendrobium (Orchidaceae).
AB  - Plants of the Dendrobium genus are orchids with not only ornamental value but
      also high medicinal value. To understand the genetic basis of variations in
      active ingredients of the stem total polysaccharide contents (STPCs) among
      different Dendrobium species, it is of paramount importance to understand the
      mechanism of STPC formation and identify genes affecting its process at the whole
      genome level. Here, we report the first high-density single-nucleotide
      polymorphism (SNP) integrated genetic map with a good genome coverage of
      Dendrobium. The specific-locus amplified fragment sequencing (SLAF-seq)
      technology led to identification of 7,013,400 SNPs from 1,503,626 high-quality
      SLAF markers from two parents (Dendrobium moniliforme ? * Dendrobium officinale
      ?) and their interspecific F1 hybrid population. The final genetic map contained
      8, 573 SLAF markers, covering 19 linkage groups (LGs). This genetic map spanned a
      length of 2,737.49 cM, where the average distance between markers is 0.32 cM. In
      total, 5 quantitative trait loci (QTL) related to STPC were identified, 3 of
      which have candidate genes within the confidence intervals of these stable QTLs
      based on the D. officinale genome sequence. This study will build a foundation up
      for the mapping of other medicinal-related traits and provide an important
      reference for the molecular breeding of these Chinese herb.

PMID- 29636769
TI  - Population Structure and Genomic Breed Composition in an Angus-Brahman Crossbred
      Cattle Population.
AB  - Crossbreeding is a common strategy used in tropical and subtropical regions to
      enhance beef production, and having accurate knowledge of breed composition is
      essential for the success of a crossbreeding program. Although pedigree records
      have been traditionally used to obtain the breed composition of crossbred cattle,
      the accuracy of pedigree-based breed composition can be reduced by inaccurate
      and/or incomplete records and Mendelian sampling. Breed composition estimation
      from genomic data has multiple advantages including higher accuracy without being
      affected by missing, incomplete, or inaccurate records and the ability to be used
      as independent authentication of breed in breed-labeled beef products. The
      present study was conducted with 676 Angus-Brahman crossbred cattle with genotype
      and pedigree information to evaluate the feasibility and accuracy of using
      genomic data to determine breed composition. We used genomic data in parametric
      and non-parametric methods to detect population structure due to differences in
      breed composition while accounting for the confounding effect of close familial
      relationships. By applying principal component analysis (PCA) and the maximum
      likelihood method of ADMIXTURE to genomic data, it was possible to successfully
      characterize population structure resulting from heterogeneous breed ancestry,
      while accounting for close familial relationships. PCA results offered additional
      insight into the different hierarchies of genetic variation structuring. The
      first principal component was strongly correlated with Angus-Brahman proportions,
      and the second represented variation within animals that have a relatively more
      extended Brangus lineage-indicating the presence of a distinct pattern of genetic
      variation in these cattle. Although there was strong agreement between breed
      proportions estimated from pedigree and genetic information, there were
      significant discrepancies between these two methods for certain animals. This was
      most likely due to inaccuracies in the pedigree-based estimation of breed
      composition, which supported the case for using genomic information to complement
      and/or replace pedigree information when estimating breed composition. Comparison
      with a supervised analysis where purebreds are used as the training set suggest
      that accurate predictions can be achieved even in the absence of purebred
      population information.

PMID- 29636768
TI  - Abscisic Acid and Gibberellins Antagonistically Mediate Plant Development and
      Abiotic Stress Responses.
AB  - Phytohormones regulate numerous important biological processes in plant
      development and biotic/abiotic stress response cascades. More than 50 and 100
      years have passed since the initial discoveries of the phytohormones abscisic
      acid (ABA) and gibberellins (GA), respectively. Over the past several decades,
      numerous elegant studies have demonstrated that ABA and GA antagonistically
      regulate many plant developmental processes, including seed maturation, seed
      dormancy and germination, root initiation, hypocotyl and stem elongation, and
      floral transition. Furthermore, as a well-established stress hormone, ABA plays a
      key role in plant responses to abiotic stresses, such as drought, flooding,
      salinity and low temperature. Interestingly, recent evidence revealed that GA are
      also involved in plant response to adverse environmental conditions.
      Consequently, the complex crosstalk networks between ABA and GA, mediated by
      diverse key regulators, have been extensively investigated and documented. In
      this updated mini-review, we summarize the most recent advances in our
      understanding of the antagonistically regulatory roles of ABA and GA in different
      stages of plant development and in various plant-environment interactions,
      focusing on the crosstalk between ABA and GA at the levels of phytohormone
      metabolism and signal transduction.

PMID- 29636770
TI  - "Exosomics"-A Review of Biophysics, Biology and Biochemistry of Exosomes With a
      Focus on Human Breast Milk.
AB  - Exosomes are biomolecular nanostructures released from cells. They carry specific
      biomolecular information and are mainly researched for their exquisite properties
      as a biomarker source and delivery system. We introduce exosomes in the context
      of other extracellular vesicles, describe their biophysical isolation and
      characterisation and discuss their biochemical profiling. Motivated by our
      interest in early-life nutrition and health, and corresponding studies enrolling
      lactating mothers and their infants, we zoom into exosomes derived from human
      breast milk. We argue that these should be more extensively studied at proteomic
      and micronutrient profiling level, because breast milk exosomes provide a more
      specific window into breast milk quality from an immunological (proteomics) and
      nutritional (micronutrient) perspective. Such enhanced breast milk exosome
      profiling would thereby complement and enrich the more classical whole breast
      milk analysis and is expected to deliver more functional insights than the rather
      descriptive analysis of human milk, or larger fractions thereof, such as milk fat
      globule membrane. We substantiate our arguments by a bioinformatic analysis of
      two published proteomic data sets of human breast milk exosomes.

PMID- 29636772
TI  - Bioactivities of Traditional Medicinal Plants in Alexandria.
AB  - In traditional folklore, medicinal herbs play a vital role in the prevention and
      treatment of microbial diseases. In the present study, the phenolic profiles of
      the medicinal plants Asparagus aethiopicus L., Citrullus colocynthis L., Senna
      alexandrina L., Kalanchoe delagoensis L., Gasteria pillansii L., Cymbopogon
      citratus, Brassica juncea, and Curcuma longa L. were determined by high
      performance liquid chromatography with a diode-array detector method. The results
      revealed rich sources of important compounds such as robinin in the fruits and
      leaves of A. aethiopicus; caffeic acid in the tubers of A. aethiopicus and
      quercitrin in the leaves of G. pillansii. Further, relatively high antioxidant,
      antibacterial, and antifungal activities were observed in C. colocynthis fruit
      coat, S. alexandrina pods, and A. aethiopicus leaves, respectively. The
      relatively higher the bioactivities of plants extracts associated with the
      phenols in these plants, in particular, the more abundant the phenols. Therefore,
      it was concluded that the fruit coat of C. colocynthis, pods of S. alexandrina,
      and leaves of A. aethiopicus might be excellent sources of natural products.
      These plant extracts also have a wide spectrum of antimicrobial activities that
      could be used in the pharmaceutical industries and to control diseases.

PMID- 29636771
TI  - Mitochonic acid 5 activates the MAPK-ERK-yap signaling pathways to protect mouse
      microglial BV-2 cells against TNFalpha-induced apoptosis via increased Bnip3
      related mitophagy.
AB  - Background: The regulation of microglial function via mitochondrial homeostasis
      is important in the development of neuroinflammation. The underlying mechanism
      for this regulatory function remains unclear. In this study, we investigated the
      protective role of mitochonic acid 5 (MA-5) in microglial mitochondrial apoptosis
      following TNFalpha-induced inflammatory injury. Methods: TNFalpha was used to
      induce inflammatory injury in mouse microglial BV-2 cells with and without prior
      MA-5 treatment. Cellular apoptosis was assessed using the MTT and TUNEL assays.
      Mitochondrial functions were evaluated via mitochondrial membrane potential JC-1
      staining, ROS flow cytometry analysis, mPTP opening assessment, and
      immunofluorescence of cyt-c. Mitophagy was examined using western blots and
      immunofluorescence. The pathways analysis was carried out using western blots and
      immunofluorescence with a pathway blocker. Results: Our results demonstrated that
      TNFalpha induced apoptosis in the microglial BV-2 cell line by activating the
      caspase-9-dependent mitochondrial apoptotic pathway. Mechanistically,
      inflammation reduced mitochondrial potential, induced ROS production, and
      contributed to the leakage of mitochondrial pro-apoptotic factors into the
      cytoplasm. The inflammatory response reduced cellular energy metabolism and
      increased oxidative stress. By contrast, treatment with MA-5 reduced
      mitochondrial apoptosis via upregulation of mitophagy. Increased mitophagy
      degraded damaged mitochondria, disrupting mitochondrial apoptosis, neutralizing
      ROS overproduction, and improving cellular energy production. We also identified
      that MA-5 regulated mitophagy via Bnip3 through the MAPK-ERK-Yap signaling
      pathway. Inhibiting this signaling pathway or knocking down Bnip3 expression
      prevented MA-5 from having beneficial effects on mitochondrial homeostasis and
      increased microglial apoptosis. Conclusions: After TNFalpha-induced inflammatory
      injury, MA-5 affects microglial mitochondrial homeostasis in a manner mediated
      via the amplification of protective, Bnip3-related mitophagy, which is mediated
      via the MAPK-ERK-Yap signaling pathway.

PMID- 29636773
TI  - Total Flavonoids from Oroxylum indicum Induce Apoptosis via PI3K/Akt/PTEN
      Signaling Pathway in Liver Cancer.
AB  - Total flavonoids (TF), derived from the seeds of Oroxylum indicum (L.) Vent.,
      possess many pharmacological functions. In the present study, H22-bearing mice
      and SMMC-7721 models were employed to evaluate the antitumor activity of TF and
      to and investigate its possible mechanisms both in vitro and in vivo. Cell
      viability was evaluated by MTT assay; cell apoptosis rate was analyzed via
      Annexin V-FITC/PI double staining by flow cytometer. Meanwhile, the expressions
      of apoptosis-related mRNA and proteins were evaluated by RT-PCR and Western blot
      analysis. The results revealed that TF could significantly inhibit the tumor
      growth, and the possible mechanism was related to the effect of inducing tumor
      cells apoptosis through PI3K/Akt/PTEN signaling pathway. This study has provided
      a theoretical basis for the further development and application of TF as
      antitumor drugs.

PMID- 29636774
TI  - Flavanones from Sedum sarmentosum Bunge Alleviate CCl4-Induced Liver Fibrosis in
      Rats by Targeting TGF-beta1/TbetaR/Smad Pathway In Turn Inhibiting Epithelial
      Mesenchymal Transition.
AB  - Objective: The aim of the study is to evaluate the therapeutic effects of
      flavanones from Sedum sarmentosum Bunge (FSSB) on CCl4-induced liver fibrosis in
      rats and the underlying mechanisms of action. Methods: An experimental model of
      liver fibrosis was established by subcutaneous injection of rats with CCl4 (40%
      v/v, 3 ml/kg) twice per week for six weeks. FSSB (100, 200, and 400 mg/kg) was
      intragastrically administered once per day consecutively for five weeks. Results:
      Our results showed that FSSB significantly attenuated CCl4-induced liver fibrosis
      as evidenced by reducing the elevated levels of serum biochemical indexes and
      improving the histological changes, including decreasing the elevation in serum
      alanine transaminase (ALT), aspartate transaminase (AST), hyaluronic acid (HA),
      and laminin (LN) level, reducing infiltration of inflammatory cells and collagen
      fibers in liver tissue. In addition, compared to the model group, FSSB markedly
      downregulated the protein and mRNA expression of TGF-beta1, TGF-beta1 receptors I
      and II (TbetaRI and TbetaRII), Smad2, Smad3, and Vimentin in liver tissue, at the
      mean time upregulating the expression of Smad7 and E-cadherin. Conclusions: The
      results suggest that FSSB alleviated CCl4-induced liver fibrosis probably through
      inhibition of TGF-beta/TbetaR/Smad pathway in turn inhibiting epithelial
      mesenchymal transition.

PMID- 29636775
TI  - Shaofu Zhuyu Decoction Regresses Endometriotic Lesions in a Rat Model.
AB  - The current therapies for endometriosis are restricted by various side effects
      and treatment outcome has been less than satisfactory. Shaofu Zhuyu Decoction
      (SZD), a classic traditional Chinese medicinal (TCM) prescription for
      dysmenorrhea, has been widely used in clinical practice by TCM doctors to relieve
      symptoms of endometriosis. The present study aimed to investigate the effects of
      SZD on a rat model of endometriosis. Forty-eight female Sprague-Dawley rats with
      regular estrous cycles went through autotransplantation operation to establish
      endometriosis model. Then 38 rats with successful ectopic implants were
      randomized into two groups: vehicle- and SZD-treated groups. The latter were
      administered SZD through oral gavage for 4 weeks. By the end of the treatment
      period, the volume of the endometriotic lesions was measured, the
      histopathological properties of the ectopic endometrium were evaluated, and
      levels of proliferating cell nuclear antigen (PCNA), CD34, and hypoxia inducible
      factor- (HIF-) 1alpha in the ectopic endometrium were detected with
      immunohistochemistry. Furthermore, apoptosis was assessed using the terminal
      deoxynucleotidyl transferase (TdT) deoxyuridine 5'-triphosphate (dUTP) nick-end
      labeling (TUNEL) assay. In this study, SZD significantly reduced the size of
      ectopic lesions in rats with endometriosis, inhibited cell proliferation,
      increased cell apoptosis, and reduced microvessel density and HIF-1alpha
      expression. It suggested that SZD could be an effective therapy for the treatment
      and prevention of endometriosis recurrence.

PMID- 29636776
TI  - Efficacy and Safety of Wei Bi Mei, a Chinese Herb Compound, as an Alternative to
      Bismuth for Eradication of Helicobacter pylori.
AB  - Bismuth-containing quadruple therapy has been recommended as the first line of
      treatment in areas of high clarithromycin or metronidazole resistance. However,
      safety concerns of bismuth agents have long been raised. We first assessed the
      efficacy and safety of Wei Bi Mei granules, which are bismuth compounds
      consisting of three synthetic drugs and five medicinal herbs, compared to bismuth
      aluminate and colloidal bismuth subcitrate (CBS) in H. pylori-infected mouse
      model. We then used atomic fluorescence spectroscopy and autometallography to
      measure the accumulation of three bismuth agents in the brain, heart, liver, and
      kidneys in adult Sprague-Dawley rats. We also evaluated the safety of bismuth
      agents by conducting clinical biochemistry tests in blood samples of experimental
      animals. Wei Bi Mei granules exhibited the highest efficacy of anti-H. pylori
      activity and yielded the lowest bismuth accumulation when compared to CBS and
      bismuth aluminate. Our findings show that Wei Bi Mei granules are a safe Chinese
      medicinal herb with potent anti-H. pylori activity and can be considered as an
      alternative to current bismuth compounds. Thus, Wei Bi Mei granules merit further
      evaluation, particularly with regard to efficacy and safety when they are
      combined with other H. pylori eradication medications in the clinical setting.

PMID- 29636777
TI  - Antitumor Mechanisms of Curcumae Rhizoma Based on Network Pharmacology.
AB  - Curcumae Rhizoma, a traditional Chinese medication, is commonly used in both
      traditional treatment and modern clinical care. Its anticancer effects have
      attracted a great deal of attention, but the mechanisms of action remain obscure.
      In this study, we screened for the active compounds of Curcumae Rhizoma using a
      drug-likeness approach. Candidate protein targets with functions related to
      cancer were predicted by reverse docking and then checked by manual search of the
      PubMed database. Potential target genes were uploaded to the GeneMANIA server and
      DAVID 6.8 database for analysis. Finally, compound-target, target-pathway, and
      compound-target-pathway networks were constructed using Cytoscape 3.3. The
      results revealed that the anticancer activity of Curcumae Rhizoma potentially
      involves 13 active compounds, 33 potential targets, and 31 signaling pathways,
      thus constituting a "multiple compounds, multiple targets, and multiple pathways"
      network corresponding to the concept of systematic actions in TCM. These findings
      provide an overview of the anticancer action of Curcumae Rhizoma from a network
      perspective, as well as setting an example for future studies of other materials
      used in TCM.

PMID- 29636778
TI  - Patient's Decision to Disclose the Use of Traditional and Complementary Medicine
      to Medical Doctor: A Descriptive Phenomenology Study.
AB  - Nondisclosure of traditional and complementary medicine (T&CM) use may cause
      individual to be at risk of undue harm. This study aimed to explore patient's
      experience and views on their decision to disclose the use of T&CM to the doctor.
      An exploratory qualitative study using in-depth interview involving 10 primary
      care clinics attendees in Kuching was conducted. The results indicated that
      disclosure of T&CM use will motivate them to get information, increase doctor's
      awareness, and get support from family and friends for disclosure. Fear of
      negative relationship and negative response from doctors was a barrier for
      disclosure. Doctor's interpersonal and communication skills of being involved,
      treating patients respectfully, listening attentively, respecting privacy, and
      taking time for the patient were a critical component for disclosure.
      Intrapersonal trust regarding doctor influences their satisfaction on healthcare.
      Women are more open and receptive to a health concern and expressing negative
      emotions and tend to share problems, whereas men always described themselves as
      healthy, tended to keep their own personal feeling to themselves, and tended to
      not share. The doctor should consider gender differences in disclosure, their
      attitude towards T&CM use, and gained patient's trust in the delivery of
      healthcare services. Good interpersonal and communication skills must be
      maintained between doctor and patients.

PMID- 29636779
TI  - Differential Regulation of NF-kappaB and Nrf2 by Bojungikki-Tang Is Associated
      with Suppressing Lung Inflammation.
AB  - Bojungikki-tang (BT), an Asian herbal remedy, has been prescribed to increase the
      vitality of debilitated patients. Since a compromised, weakened vitality often
      leads to illness, BT has been widely used to treat various diseases. However,
      little is known about the mechanism by which BT exerts its effect. Given that BT
      ameliorates inflammatory pulmonary diseases including acute lung injury (ALI), we
      investigated whether BT regulates the function of key inflammatory factors such
      as NF-kappaB and Nrf2, contributing to suppressing inflammation. Results show
      that BT interrupted the nuclear localization of NF-kappaB and suppressed the
      expression of the NF-kappaB-dependent genes in RAW 264.7 cells. In similar
      experiments, BT induced the nuclear localization of Nrf2 and the expression of
      the Nrf2-dependent genes. In a lipopolysaccharide-induced ALI mouse model, a
      single intratracheal administration of BT to mouse lungs ameliorated alveolar
      structure and suppressed the expression of proinflammatory cytokine genes and
      neutrophil infiltration to mouse lungs. Therefore, our findings suggest that
      suppression of NF-kappaB and activation of Nrf2, by which BT suppresses
      inflammation, are ways for BT to exert its effect.

PMID- 29636780
TI  - Herba Artemisiae Capillaris Extract Prevents the Development of Streptozotocin
      Induced Diabetic Nephropathy of Rat.
AB  - Diabetic nephropathy (DN) is a major cause of end-stage renal disease throughout
      the world; until now there is no specific drug available. In this work, we use
      herba artemisiae capillaris extract (HACE) to alleviate renal fibrosis
      characterized by the excessive accumulation of extracellular matrix (ECM) in
      rats, aiming to investigate the protective effect of the HACE on DN. We found
      that the intragastric treatment of high-dose HACE could reverse the effect of
      streptozotocin not only to decrease the level of blood glucose and blood lipid in
      different degree but also further to improve renal functions. It is worth
      mentioning that the effect of HACE treatment was comparable to the positive drug
      benazepril. Moreover, we found that HACE treatment could on one hand inhibit
      oxidative stress in DN rats through regulating enzymatic activity for scavenging
      reactive oxygen species and on the other hand increase the ECM degradation
      through regulating the activity of metalloproteinase-2 (MMP-2) and the expression
      of tissue transglutaminase (tTG), which explained why HACE treatment inhibited
      ECM accumulation. On the basis of above experimental results, we conclude that
      HACE prevents DN development in a streptozotocin-induced DN rat model, and HACE
      is a promising candidate to cure DN in clinic.

PMID- 29636781
TI  - Traditional Herbal Formula NPC01 Exerts Antiangiogenic Effects through Inhibiting
      the PI3K/Akt/mTOR Signaling Pathway in Nasopharyngeal Carcinoma Cells.
AB  - Antiangiogenic therapy is vital in nasopharyngeal carcinoma (NPC) treatment.
      NPC01 has already been successfully used in treating patients with NPC in
      clinical practice and exerted an excellent antiangiogenetic effect. However, the
      potential molecular mechanism underlying the antitumor effect of NPC01 has not
      been well explored. The present study demonstrated that NPC01 could significantly
      inhibit cell proliferation and induce cell apoptosis in a dose-dependent manner
      in human NPC cell lines. Furthermore, NPC01 exerted antiproliferative and
      antiangiogenic effects in NPC xenograft mice. Moreover, the study showed that
      NPC01 could significantly decrease the expression of angiogenesis-associated
      factors including hypoxia-inducible factor-1alpha and vascular endothelial growth
      factor. Additionally, the decreased expression of these angiogenesis-associated
      factors could be due to the inhibition of the phosphoinositide 3-kinase
      (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling
      pathway (PI3K/Akt/mTOR). In conclusion, the results proposed that NPC01 could
      exert its antitumor effect by suppressing the PI3K/Akt/mTOR signaling pathway.
      Further studies are warranted to elucidate the molecular mechanism.

PMID- 29636782
TI  - A Systematic Review of Herbal Medicine for Chemotherapy Induced Peripheral
      Neuropathy.
AB  - Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse
      effect in cancer patients. The aim of this review was to assess the effectiveness
      of herbal medicine in preventing and treating CIPN. Methods: Randomised
      controlled trials were included in this review. Extracting and assessing the data
      independently, two authors searched 13 databases. Results: Twenty-eight trials
      involving 2174 patients met the inclusion criteria. Although there were some
      exceptions, the methodological quality was typically low. Seventeen trials
      reported the incidence rate of CIPN assessed by various tools and 14 showed a
      significant difference regarding the decrease of the incidence rate between the
      two groups. For clinical improvement, 12 trials reported it using various tools
      and 10 showed a significant difference between two groups. Two cases of adverse
      events occurred in one trial; the other nine trials reported no adverse events.
      Conclusions: We found that herbal medicines in combination with and/or without
      other therapies potentially have preventive or therapeutic effects on CIPN.
      However, conclusions cannot be drawn because of the generally low quality of the
      methodology, the clinical heterogeneity, and the small sample size for each
      single herbal medicine. Trials that are more rigorous and report sufficient
      methodological data are needed.

PMID- 29636783
TI  - Xiaoqinglong Decoction Attenuates Chronic Obstructive Pulmonary Disease in Rats
      via Inhibition of Autophagy.
AB  - Effective treatment for chronic obstructive pulmonary disease (COPD) and
      knowledge of the underlying mechanism are urgently required. Xiaoqinglong
      decoction (XQL) is widely used to treat COPD in Traditional Chinese Medicine, but
      the mechanism remains unclear. In this study, we tested the hypothesis that XQL
      ameliorates COPD via inhibition of autophagy in lung tissue on a rat model. Rats
      were divided into five groups, namely, Control group, COPD group, COPD + XQL
      group, COPD + Rapamycin group, and COPD + XQL + Rapamycin group. Pathological
      changes on cellular and molecular levels, apoptosis reflected by TdT-mediated
      dUTP Nick-End Labeling (TUNEL) assay, and autophagy represented by LC3II/LC3I
      ratio and p62 level were investigated for each group. Compared with the Control
      group, COPD rats exhibited structural changes and activated inflammation in the
      lung tissue, together with enhanced apoptosis and elevated autophagy biomarkers.
      XQL treatment significantly ameliorated these changes, while rapamycin augmented
      them. These data altogether confirmed the involvement of autophagy in the
      pathogenesis of COPD and suggested that XQL attenuates COPD via inhibition of
      autophagy.

PMID- 29636784
TI  - Acute Effects of Tai Chi Training on Cognitive and Cardiovascular Responses in
      Late Middle-Aged Adults: A Pilot Study.
AB  - This study explored the immediate effects of Tai Chi (TC) training on attention
      and meditation, perceived stress level, heart rate, oxygen saturation level in
      blood, and palmar skin temperature in late middle-aged adults. Twenty TC
      practitioners and 20 nonpractitioners volunteered to join the study. After
      baseline measurements were taken, the TC group performed TC for 10 minutes while
      their cognitive states and cardiovascular responses were concurrently monitored.
      The control group rested for the same duration in a standing position. Both
      groups were then reassessed. The participants' attention and meditation levels
      were measured using electroencephalography; stress levels were measured using
      Perceived Stress Scale; heart rate and blood oxygenation were measured using an
      oximeter; and palmar skin temperature was measured using an infrared thermometer.
      Attention level tended to increase during TC and dropped immediately thereafter
      (p < 0.001). Perceived stress level decreased from baseline to posttest in
      exclusively the TC group (p = 0.005). Heart rate increased during TC (p < 0.001)
      and decreased thereafter (p = 0.001). No significant group, time, or group-by
      time interaction effects were found in the meditation level, palmar skin
      temperature, and blood oxygenation outcomes. While a 10-minute TC training could
      temporarily improve attention and decrease perceived stress levels, it could not
      improve meditation, palmar skin temperature, or blood oxygenation among late
      middle-aged adults.

PMID- 29636785
TI  - Alleviating the Intestinal Absorption of Rhein in Rhubarb through Herb
      Compatibility in Tiaowei Chengqi Tang in Caco-2 Cells.
AB  - Tiaowei Chengqi Tang (TWCQT) is composed of rhubarb, processed liquorice, and
      Natrii Sulfas, which is used as a purgative in traditional Chinese medicine
      (TCM). This study focused on the intestinal absorption of rhein in disassembly of
      the TWCQT extracts through the Caco-2 cell monolayer model to explicate the
      possible detoxification mechanism of herb-herb compatibility in TWCQT. The
      results showed that the intestinal absorption of rhein occurred through active
      diffusion, and rhein might be composed of breast cancer resistance protein (BCRP)
      substrates. The extract of processed liquorice increased the exclusion rate and
      reduced intracellular uptake of rhein. The consistent results observed in TWCQT
      further implied that processed liquorice in TWCQT could suppress the absorption
      of rhein across the Caco-2 cell monolayer. It has therefore been concluded that
      the active ingredients of processed liquorice may play a critical role in
      reducing the intestinal absorption of rhein to alleviate the toxicity of rhubarb
      in TWCQT. Because of BCRP's involvement in rhein transport, we conjectured that
      some components in processed liquorice could inhibit the transport of rhein,
      possibly by mediating BCRP. These results would provide new insight into this
      ancient drug combination in toxicity reduction and clinical use.

PMID- 29636786
TI  - Expression of miRNAs in Serum Exosomes versus Hippocampus in Methamphetamine
      Induced Rats and Intervention of Rhynchophylline.
AB  - Objective: To compare the expressions of miRNAs (microRNAs) in serum exosomes and
      in hippocampus and to provide insights into the miRNA-mediated relationship
      between peripheral and central nervous systems in the presence of
      methamphetamine. Methods: Published results on conditioned place preference (CPP)
      in rats conditioned by methamphetamine were replicated. The expressions of miRNAs
      in serum exosomes and hippocampus were determined by gene-chip sequencing. We
      then predicted the potential target genes of selected, differentially expressed
      (DE) miRNAs and then carried out functional analysis of these target genes. We
      also verified our results by RT-qPCR. Results: Methamphetamine reward could
      greatly increase the activity time and distance in the intrinsically nonpreferred
      side of the behavioral apparatus compared with control rats (P < 0.01).
      Rhynchophylline treatment significantly counteracted these changes (P < 0.01).
      Methamphetamine-induced CPP upregulated 23 miRNAs (log2 fold change [FC] > 1, P <
      0.01) in serum exosomes, whereas rhynchophylline treatment could downregulate
      these miRNAs (log2 FC < -1, P < 0.01). Analysis of hippocampal miRNAs profiles
      found 22 DE miRNAs (log2 FC > 1 or <-1, P < 0.01). When methamphetamine induced
      CPP, 11 of those miRNAs were upregulated, whereas rhynchophylline treatment could
      downregulate these miRNAs. The other 11 miRNAs behaved in the opposite way. We
      selected six DE miRNAs from each of serum exosomes and hippocampus for target
      gene prediction and functional analysis. We found that, in both, the DE miRNAs
      and their target genes may be related to neuronal information transmission and
      synaptic transmission. Conclusions: Rhynchophylline blocked the alteration of
      behavior and the expression of some DE miRNAs induced by methamphetamine. The
      biological functions of these DE miRNAs target genes are correlated between serum
      exosomes and hippocampus. As to these biological processes and pathways which are
      involved in the development of addiction at multiple stages, we speculate that
      these DE miRNAs in serum exosomes and hippocampus are closely related to
      methamphetamine addiction.

PMID- 29636787
TI  - Ma-Huang-Fu-Zi-Xi-Xin Decoction for Allergic Rhinitis: A Systematic Review.
AB  - Background: The treatment effects and safety of Ma-Huang-Fu-Zi-Xi-Xin decoction
      for patients with allergic rhinitis have yet to be clarified. Objectives: The aim
      of this study is to evaluate the effects and safety of Ma-Huang-Fu-Zi-Xi-Xin
      decoction in patients with allergic rhinitis. Methods: We searched PubMed, EMBASE
      (Excerpta Medical Database), Cochrane Library, Chinese Cochrane Centre's
      Controlled Trials Register Platform, Wanfang Chinese Digital Periodical and
      Conference Database, China National Knowledge Infrastructure (CNKI) Database, and
      VIP Chinese Science and Technique Journals Database to collect randomized
      controlled trials of Ma-Huang-Fu-Zi-Xi-Xin decoction (MHFZXXD) for allergic
      rhinitis (AR) prior to May 8, 2017. RevMan 5.3 software was used to conduct a
      meta-analysis. GRADE methodology was applied to evaluate the evidence quality for
      each outcome. Results: Six randomized controlled trials (RCTs) involving 576
      participants (10-78 years old) were included. A meta-analysis revealed that the
      overall effect of MHFZXXD for AR was not better than western medical treatment
      (RR: 0.41; 95% CI: 0.26-0.65; P = 0.0001) for all included studies. However, the
      evidence quality of these western medical intervention studies was low or very
      low due to a high risk of bias, small sample sizes, and poor-quality design.

PMID- 29636788
TI  - Therapeutic Effect of Cucumis melo L. Extract on Insulin Resistance and the Gut
      Microbiome in Lepob/Lepob Mice.
AB  - Obesity results in the progression of metabolic disorders, especially type 2
      diabetes (T2DM). Obesity-induced insulin resistance (IR) is a causative factor of
      T2DM morbidity in obese people. It is generally held by clinicians that IR is
      caused by adiposity-related inflammation that is mediated by changes in composite
      ions in the gut microbiome. This experimental study was designed to investigate
      the effects of Cucumis melo L. (Cucumis) on obesity-induced IR in genetically
      leptin-deficient Lepob/Lepob mice. Specifically, we examined the anti
      inflammatory effects of Cucumis and the effects of Cucumis on the gut microbiota.
      We evaluated glucose control by measuring FBS, performing the OGTT, quantifying
      serum IR, calculating the HOMA-IR, and determining the lipid profiles. To see
      whether inflammation was reduced, we analyzed adipose tissue macrophages as well
      as monocytes in the blood. We also profiled the gut microbiota to determine
      whether the ratios of microbial phyla changed. We found that Cucumis improved IR
      in obese mice and relieved inflammation in adipose tissue and blood.
      Simultaneously, the microbiota composition ratios changed. In conclusion,
      administration of Cucumis improved IR by reducing inflammation, thereby changing
      the gut microbiota composition. Cucumis is thus a promising treatment for obesity
      induced insulin resistance and the inflammatory state.

PMID- 29636789
TI  - Cotton dust exposure and self-reported respiratory symptoms among textile factory
      workers in Northwest Ethiopia: a comparative cross-sectional study.
AB  - Background: Cotton dust induced respiratory disorders are dramatically increased
      over the globe, especially the problem is serious in developing countries.
      Respiratory symptoms, such as cough, phlegm, wheezing, shortness of breath, chest
      tightness, chronic bronchitis, and byssinosis are common among workers exposed to
      cotton dust. However, in Ethiopia, the magnitude of the problem is not well known
      and information is limited about the risk factors. Therefore, this study was
      aimed to assess the prevalence of respiratory symptoms and associated factors.
      Methods: A Comparative cross-sectional study design was employed. A total of 413
      (276 exposed and 137 unexposed) participants were included in the study.
      Stratified and simple random sampling techniques were used to select exposed and
      unexposed groups to cotton dust respectively. Multivariable binary logistic
      regression analyses was performed to identify variables associated with
      respiratory symptoms and adjusted odds ratio (AOR) was used to determine the
      strength of associations. Significance level was obtained at 95% confidence
      interval (CI) and p-value <=0.05. Results: The prevalence of self-reported
      respiratory symptoms was 47.8% (95% CI: 41.3, 53.7%) and 15.3% (95% CI: 9.6,
      22.3%) among exposed and control groups respectively. Sex (AOR = 2.1, 95% CI:
      1.29, 3.45), service year (AOR = 2.38, 95% CI: 1.19, 4.71) and ventilation (AOR =
      2.4, 95% CI: 1.17, 4.91) were factors significantly associated with respiratory
      symptoms. Furthermore, working department such as; ginning (AOR = 5.1, 95% CI:
      2.13, 12.16), spinning (AOR = 4.96, 95% CI: 2.18, 11.29), weaving (AOR = 5.9, 95%
      CI: 2.46, 14.27) and blowing working departments (AOR = 5.14, 95% CI: 1.4, 18.94)
      were significantly associated with respiratory disorders. Conclusions: The
      prevalence of self-reported respiratory symptoms was higher among workers exposed
      to cotton dust than unexposed workers. Sex, service year, working department and
      work unit ventilation were predictor variables for respiratory symptoms. Thus,
      reducing exposure to dust, adequate ventilation and improving the hygiene of
      working departments are needed to reduce respiratory symptoms.

PMID- 29636791
TI  - Health and social care coordination for severe and persistent mental illness in
      Australia: a mixed methods evaluation of experiences with the Partners in
      Recovery Program.
AB  - Background: Care coordination has been identified as a person-centred response to
      the difficulty in meeting the needs of people with severe and persistent mental
      illness and complex needs. This study evaluated the processes and outcomes of the
      Partners in Recovery initiative in the Australian Capital Territory, a program
      established to improve coordination of health and social care for this
      population. Methods: Client, carer and service provider experiences were
      investigated using a combination of quantitative and qualitative methods.
      Quantitative data were collected through questionnaires completed by clients (n =
      25) and service providers (n = 14). Qualitative data comprised open-ended written
      feedback from the surveys, together with semi-structured interviews with selected
      clients (n = 6), carers (n = 2), and service providers (n = 4). In both study
      elements, questions focused on dimensions of experience such as communication,
      continuity and coordination, teamwork and sustainability. Descriptive statistics
      were calculated for quantitative data; qualitative data were analysed using
      content analysis. Results: Clients were satisfied with the program across the
      majority of experience dimensions, and there was evidence of improved access to
      coordinated care. Support Facilitators (care coordinators) were central to client
      and carer reports of the impacts of the program, and to coordination between
      services through connections built at the individual level. Challenges included
      difficulties with information continuity, a lack of role clarity for service
      providers, and uncertainty about the legacy of the program given the absence of
      formal agreements connecting different services. Conclusions: The Support
      Facilitator role was critical to the success of the program. Support Facilitators
      acted as a source of stability and relational continuity for clients, while also
      enabling connections with external services through the development of individual
      level partnerships and personal networks. Systems level coordination was limited
      by communication difficulties and a lack of formalised infrastructure to support
      cooperation between services, calling into question the lasting impact of the
      program for system change.

PMID- 29636790
TI  - Getting the invite list right: a discussion of sepsis severity scoring systems in
      severe complicated intra-abdominal sepsis and randomized trial inclusion
      criteria.
AB  - Background: Severe complicated intra-abdominal sepsis (SCIAS) is a worldwide
      challenge with increasing incidence. Open abdomen management with enhanced
      clearance of fluid and biomediators from the peritoneum is a potential therapy
      requiring prospective evaluation. Given the complexity of powering multi-center
      trials, it is essential to recruit an inception cohort sick enough to benefit
      from the intervention; otherwise, no effect of a potentially beneficial therapy
      may be apparent. An evaluation of abilities of recognized predictive systems to
      recognize SCIAS patients was conducted using an existing intra-abdominal sepsis
      (IAS) database. Methods: All consecutive adult patients with a diffuse secondary
      peritonitis between 2012 and 2013 were collected from a quaternary care hospital
      in Finland, excluding appendicitis/cholecystitis. From this retrospectively
      collected database, a target population (93) of those with either ICU admission
      or mortality were selected. The performance metrics of the Third Consensus
      Definitions for Sepsis and Septic Shock based on both SOFA and quick SOFA, the
      World Society of Emergency Surgery Sepsis Severity Score (WSESSSS), the APACHE II
      score, Manheim Peritonitis Index (MPI), and the Calgary Predisposition,
      Infection, Response, and Organ dysfunction (CPIRO) score were all tested for
      their discriminant ability to identify this subgroup with SCIAS and to predict
      mortality. Results: Predictive systems with an area under-the-receiving-operating
      characteristic (AUC) curve > 0.8 included SOFA, Sepsis-3 definitions, APACHE II,
      WSESSSS, and CPIRO scores with the overall best for CPIRO. The highest
      identification rates were SOFA score >= 2 (78.4%), followed by the WSESSSS score
      >= 8 (73.1%), SOFA >= 3 (75.2%), and APACHE II >= 14 (68.8%) identification.
      Combining the Sepsis-3 septic-shock definition and WSESSS >= 8 increased
      detection to 80%. Including CPIRO score >= 3 increased this to 82.8% (Sensitivity
      SN; 83% Specificity-SP; 74%. Comparatively, SOFA >= 4 and WSESSSS >= 8 with or
      without septic-shock had 83.9% detection (SN; 84%, SP; 75%, 25% mortality).
      Conclusions: No one scoring system behaves perfectly, and all are largely
      dominated by organ dysfunction. Utilizing combinations of SOFA, CPIRO, and
      WSESSSS scores in addition to the Sepsis-3 septic shock definition appears to
      offer the widest "inclusion-criteria" to recognize patients with a high chance of
      mortality and ICU admission. Trial registration:
      https://clinicaltrials.gov/ct2/show/NCT03163095; Registered on May 22, 2017.

PMID- 29636792
TI  - "My bitterness is deeper than the ocean": understanding internalized stigma from
      the perspectives of persons with schizophrenia and their family caregivers.
AB  - Background: It is estimated that 8 million of the Chinese adult population had a
      diagnosis of schizophrenia. Stigma associated with mental illness, which is
      pervasive in the Chinese cultural context, impacts both persons with
      schizophrenia and their family caregivers. However, a review of the literature
      found a dearth of research that explored internalized stigma from the
      perspectives of both patients and their caregivers. Methods: We integrated data
      from standardized scales and narratives from semi-structured interviews obtained
      from eight family-dyads. Interview narratives about stigma were analyzed using
      directed content analysis and compared with responses from Chinese versions of
      the Internalized Stigma of Mental Illness Scale and Affiliated Stigma Scale.
      Scores from the two scales and number of text fragments were compared to identify
      consistency of responses using the two methods. Profiles from three family-dyads
      were analyzed to highlight the interactive aspect of stigma in a dyadic
      relationship. Results: Our analyses suggested that persons with schizophrenia and
      their caregivers both internalized negative valuation from their social networks
      and reduced engagement in the community. Participants with schizophrenia
      expressed a sense of shame and inferiority, spoke about being a burden to their
      family, and expressed self-disappointment as a result of having a psychiatric
      diagnosis. Caregivers expressed high level of emotional distress because of
      mental illness in the family. Family dyads varied in the extent that internalized
      stigma were experienced by patients and caregivers. Conclusions: Family plays a
      central role in caring for persons with mental illness in China. Given the
      increasingly community-based nature of mental health services delivery,
      understanding internalized stigma as a family unit is important to guide the
      development of cultural-informed treatments. This pilot study provides a method
      that can be used to collect data that take into consideration the cultural
      nuances of Chinese societies.

PMID- 29636793
TI  - Evolutionary perspectives on human infectious diseases: Challenges, advances, and
      promises.

PMID- 29636794
TI  - Complexity and biosemiotics in evolutionary ecology of zoonotic infectious
      agents.
AB  - More is not automatically better. Generation and accumulation of information
      reflecting the complexity of zoonotic diseases as ecological systems do not
      necessarily lead to improved interpretation of the obtained information and
      understanding of these complex systems. The traditional conceptual framework for
      analysis of diseases ecology is neither designed for, nor adaptable enough, to
      absorb the mass of diverse sources of relevant information. The multidirectional
      and multidimensional approaches to analyses form an inevitable part in defining a
      role of zoonotic pathogens and animal hosts considering the complexity of their
      inter-relations. And the more data we have, the more involved the interpretation
      needs to be. The keyword for defining the roles of microbes as pathogens, animals
      as hosts, and environmental parameters as infection drivers is "functional
      importance." Microbes can act as pathogens toward their host only if/when they
      recognize the animal organism as the target. The same is true when the host
      recognizes the microbe as a pathogen rather than harmless symbiont based on the
      context of its occurrence in that host. Here, we propose conceptual tools
      developed in the realm of the interdisciplinary sciences of complexity and
      biosemiotics for extending beyond the currently dominant mindset in ecology and
      evolution of infectious diseases. We also consider four distinct hierarchical
      levels of perception guiding how investigators can approach zoonotic agents, as a
      subject of their research, representing differences in emphasizing particular
      elements and their relations versus more unified systemic approaches.

PMID- 29636795
TI  - Insights from agriculture for the management of insecticide resistance in disease
      vectors.
AB  - Key to contemporary management of diseases such as malaria, dengue, and
      filariasis is control of the insect vectors responsible for transmission.
      Insecticide-based interventions have contributed to declines in disease burdens
      in many areas, but this progress could be threatened by the emergence of
      insecticide resistance in vector populations. Insecticide resistance is likewise
      a major concern in agriculture, where insect pests can cause substantial yield
      losses. Here, we explore overlaps between understanding and managing insecticide
      resistance in agriculture and in public health. We have used the Global Plan for
      Insecticide Resistance Management in malaria vectors, developed under the
      auspices of the World Health Organization Global Malaria Program, as a framework
      for this exploration because it serves as one of the few cohesive documents for
      managing a global insecticide resistance crisis. Generally, this comparison
      highlights some fundamental differences between insect control in agriculture and
      in public health. Moreover, we emphasize that the success of insecticide
      resistance management strategies is strongly dependent on the biological
      specifics of each system. We suggest that the biological, operational, and
      regulatory differences between agriculture and public health limit the wholesale
      transfer of knowledge and practices from one system to the other. Nonetheless,
      there are some valuable insights from agriculture that could assist in advancing
      the existing Global Plan for Insecticide Resistance Management framework.

PMID- 29636797
TI  - Empirical and theoretical investigation into the potential impacts of insecticide
      resistance on the effectiveness of insecticide-treated bed nets.
AB  - In spite of widespread insecticide resistance in vector mosquitoes throughout
      Africa, there is limited evidence that long-lasting insecticidal bed nets (LLINs)
      are failing to protect against malaria. Here, we showed that LLIN contact in the
      course of host-seeking resulted in higher mortality of resistant Anopheles spp.
      mosquitoes than predicted from standard laboratory exposures with the same net.
      We also found that sublethal contact with an LLIN caused a reduction in blood
      feeding and subsequent host-seeking success in multiple lines of resistant
      mosquitoes from the laboratory and the field. Using a transmission model, we
      showed that when these LLIN-related lethal and sublethal effects were accrued
      over mosquito lifetimes, they greatly reduced the impact of resistance on malaria
      transmission potential under conditions of high net coverage. If coverage falls,
      the epidemiological impact is far more pronounced. Similarly, if the intensity of
      resistance intensifies, the loss of malaria control increases nonlinearly. Our
      findings help explain why insecticide resistance has not yet led to wide-scale
      failure of LLINs, but reinforce the call for alternative control tools and
      informed resistance management strategies.

PMID- 29636796
TI  - Putting evolution in elimination: Winning our ongoing battle with evolving
      malaria mosquitoes and parasites.
AB  - Since 2000, the world has made significant progress in reducing malaria morbidity
      and mortality, and several countries in Africa, South America and South-East Asia
      are working hard to eliminate the disease. These elimination efforts continue to
      rely heavily on antimalarial drugs and insecticide-based interventions, which
      remain the cornerstones of malaria treatment and prevention. However, resistance
      has emerged against nearly every antimalarial drug and insecticide that is
      available. In this review we discuss the evolutionary consequences of the way we
      currently implement antimalarial interventions, which is leading to resistance
      and may ultimately lead to control failure, but also how evolutionary principles
      can be applied to extend the lifespan of current and novel interventions. A
      greater understanding of the general evolutionary principles that are at the core
      of emerging resistance is urgently needed if we are to develop improved
      resistance management strategies with the ultimate goal to achieve a malaria-free
      world.

PMID- 29636798
TI  - Altered life history strategies protect malaria parasites against drugs.
AB  - Drug resistance has been reported against all antimalarial drugs, and while
      parasites can evolve classical resistance mechanisms (e.g., efflux pumps), it is
      also possible that changes in life history traits could help parasites evade the
      effects of treatment. The life history of malaria parasites is governed by an
      intrinsic resource allocation problem: specialized stages are required for
      transmission, but producing these stages comes at the cost of producing fewer of
      the forms required for within-host survival. Drug treatment, by design, alters
      the probability of within-host survival, and so should alter the costs and
      benefits of investing in transmission. Here, we use a within-host model of
      malaria infection to predict optimal patterns of investment in transmission in
      the face of different drug treatment regimes and determine the extent to which
      alternative patterns of investment can buffer the fitness loss due to drugs. We
      show that over a range of drug doses, parasites are predicted to adopt
      "reproductive restraint" (investing more in asexual replication and less in
      transmission) to maximize fitness. By doing so, parasites recoup some of the
      fitness loss imposed by drugs, though as may be expected, increasing dose reduces
      the extent to which altered patterns of transmission investment can benefit
      parasites. We show that adaptation to drug-treated infections could result in
      more virulent infections in untreated hosts. This work emphasizes that in
      addition to classical resistance mechanisms, drug treatment generates selection
      for altered parasite life history. Understanding how any shifts in life history
      will alter the efficacy of drugs, as well as any limitations on such shifts, is
      important for evaluating and predicting the consequences of drug treatment.

PMID- 29636799
TI  - Transmission traits of malaria parasites within the mosquito: Genetic variation,
      phenotypic plasticity, and consequences for control.
AB  - Evaluating the risk of emergence and transmission of vector-borne diseases
      requires knowledge of the genetic and environmental contributions to pathogen
      transmission traits. Compared to the significant effort devoted to understanding
      the biology of malaria transmission from vertebrate hosts to mosquito vectors,
      the strategies that malaria parasites have evolved to maximize transmission from
      vectors to vertebrate hosts have been largely overlooked. While determinants of
      infection success within the mosquito host have recently received attention, the
      causes of variability for other key transmission traits of malaria, namely the
      duration of parasite development and its virulence within the vector, as well as
      its ability to alter mosquito behavior, remain largely unknown. This important
      gap in our knowledge needs to be bridged in order to obtain an integrative view
      of the ecology and evolution of malaria transmission strategies. Associations
      between transmission traits also need to be characterized, as they trade-offs and
      constraints could have important implications for understanding the evolution of
      parasite transmission. Finally, theoretical studies are required to evaluate how
      genetic and environmental influences on parasite transmission traits can shape
      malaria dynamics and evolution in response to disease control.

PMID- 29636801
TI  - The effects of subcurative praziquantel treatment on life-history traits and
      trade-offs in drug-resistant Schistosoma mansoni.
AB  - Natural selection acts on all organisms, including parasites, to maximize
      reproductive fitness. Drug resistance traits are often associated with life
      history costs in the absence of treatment. Schistosomiasis control programmes
      rely on mass drug administration to reduce human morbidity and mortality.
      Although hotspots of reduced drug efficacy have been reported, resistance is not
      widespread. Using Bayesian state-space models (SSMs) fitted to data from an in
      vivo laboratory system, we tested the hypothesis that the spread of resistant
      Schistosoma mansoni may be limited by life-history costs not present in
      susceptible counterparts. S. mansoni parasites from a praziquantel-susceptible
      (S), a praziquantel-resistant (R) or a mixed line of originally resistant and
      susceptible parasites (RS) were exposed to a range of praziquantel doses.
      Parasite numbers at each life stage were quantified in their molluscan
      intermediate and murine definitive hosts across four generations, and SSMs were
      used to estimate key life-history parameters for each experimental group over
      time. Model outputs illustrated that parasite adult survival and fecundity in the
      murine host decreased across all lines, including R, with increasing drug
      pressure. Trade-offs between adult survival and fecundity were observed in all
      untreated lines, and these remained strong in S with praziquantel pressure. In
      contrast, trade-offs between adult survival and fecundity were lost under
      praziquantel pressure in R. As expected, parasite life-history traits within the
      molluscan host were complex, but trade-offs were demonstrated between parasite
      establishment and cercarial output. The observed trade-offs between generations
      within hosts, which were modified by praziquantel treatment in the R line, could
      limit the spread of R parasites under praziquantel pressure. Whilst such complex
      life-history costs may be difficult to detect using standard empirical methods,
      we demonstrate that SSMs provide robust estimates of life-history parameters,
      aiding our understanding of costs and trade-offs of resistant parasites within
      this system and beyond.

PMID- 29636800
TI  - Evolutionary ecology of Chagas disease; what do we know and what do we need?
AB  - The aetiological agent of Chagas disease, Trypanosoma cruzi, is a key human
      pathogen afflicting most populations of Latin America. This vectorborne parasite
      is transmitted by haematophageous triatomines, whose control by large-scale
      insecticide spraying has been the main strategy to limit the impact of the
      disease for over 25 years. While those international initiatives have been
      successful in highly endemic areas, this systematic approach is now challenged by
      the emergence of insecticide resistance and by its low efficacy in controlling
      species that are only partially adapted to human habitat. In this contribution,
      we review evidences that Chagas disease control shall now be entering a second
      stage that will rely on a better understanding of triatomines adaptive potential,
      which requires promoting microevolutionary studies and -omic approaches.
      Concomitantly, we show that our knowledge of the determinants of the evolution of
      T. cruzi high diversity and low virulence remains too limiting to design
      evolution-proof strategies, while such attributes may be part of the future of
      Chagas disease control after the 2020 WHO's target of regional elimination of
      intradomiciliary transmission has been reached. We should then aim at developing
      a theory of T. cruzi virulence evolution that we anticipate to provide an
      interesting enrichment of the general theory according to the specificities of
      transmission of this very generalist stercorarian trypanosome. We stress that
      many ecological data required to better understand selective pressures acting on
      vector and parasite populations are already available as they have been
      meticulously accumulated in the last century of field research. Although more
      specific information will surely be needed, an effective research strategy would
      be to integrate data into the conceptual and theoretical framework of
      evolutionary ecology and life-history evolution that provide the quantitative
      backgrounds necessary to understand and possibly anticipate adaptive responses to
      public health interventions.

PMID- 29636802
TI  - Opportunities and challenges for modelling epidemiological and evolutionary
      dynamics in a multihost, multiparasite system: Zoonotic hybrid schistosomiasis in
      West Africa.
AB  - Multihost multiparasite systems are evolutionarily and ecologically dynamic,
      which presents substantial trans-disciplinary challenges for elucidating their
      epidemiology and designing appropriate control. Evidence for hybridizations and
      introgressions between parasite species is gathering, in part in line with
      improvements in molecular diagnostics and genome sequencing. One major system
      where this is becoming apparent is within the Genus Schistosoma, where
      schistosomiasis represents a disease of considerable medical and veterinary
      importance, the greatest burden of which occurs in sub-Saharan Africa.
      Interspecific hybridizations and introgressions bring an increased level of
      complexity over and above that already inherent within multihost, multiparasite
      systems, also representing an additional source of genetic variation that can
      drive evolution. This has the potential for profound implications for the control
      of parasitic diseases, including, but not exclusive to, widening host range,
      increased transmission potential and altered responses to drug therapy. Here, we
      present the challenging case example of haematobium group Schistosoma spp.
      hybrids in West Africa, a system involving multiple interacting parasites and
      multiple definitive hosts, in a region where zoonotic reservoirs of
      schistosomiasis were not previously considered to be of importance. We consider
      how existing mathematical model frameworks for schistosome transmission could be
      expanded and adapted to zoonotic hybrid systems, exploring how such model
      frameworks can utilize molecular and epidemiological data, as well as the
      complexities and challenges this presents. We also highlight the opportunities
      and value such mathematical models could bring to this and a range of similar
      multihost, multi and cross-hybridizing parasites systems in our changing world.

PMID- 29636804
TI  - Adaptive evolution during the establishment of European avian-like H1N1 influenza
      A virus in swine.
AB  - An H1N1 subtype influenza A virus with all eight gene segments derived from wild
      birds (including mallards), ducks and chickens, caused severe disease outbreaks
      in swine populations in Europe beginning in 1979 and successfully adapted to form
      the European avian-like swine (EA-swine) influenza lineage. Genes of the EA-swine
      lineage that are clearly segregated from its closest avian relatives continue to
      circulate in swine populations globally and represent a unique opportunity to
      study the adaptive process of an avian-to-mammalian cross-species transmission.
      Here, we used a relaxed molecular clock model to test whether the EA-swine virus
      originated through the introduction of a single avian ancestor as an entire
      genome, followed by an analysis of host-specific selection pressures among
      different gene segments. Our data indicated independent introduction of gene
      segments via transmission of avian viruses into swine followed by reassortment
      events that occurred at least 1-4 years prior to the EA-swine outbreak. All EA
      swine gene segments exhibit greater selection pressure than avian viruses,
      reflecting both adaptive pressures and relaxed selective constraints that are
      associated with host switching. Notably, we identified key amino acid mutations
      in the viral surface proteins (H1 and N1) that play a role in adaptation to new
      hosts. Following the establishment of EA-swine lineage, we observed an increased
      frequency of intrasubtype reassortment of segments compared to the earlier
      strains that has been associated with adaptive amino acid replacements, disease
      severity and vaccine escape. Taken together, our study provides key insights into
      the adaptive changes in viral genomes following the transmission of avian
      influenza viruses to swine and the early establishment of the EA-swine lineage.

PMID- 29636805
TI  - Inferring epidemiologic dynamics from viral evolution: 2014-2015 Eurasian/North
      American highly pathogenic avian influenza viruses exceed transmission threshold,
      R0 = 1, in wild birds and poultry in North America.
AB  - Highly pathogenic avian influenza virus (HPAIV) is a multihost pathogen with
      lineages that pose health risks for domestic birds, wild birds, and humans. One
      mechanism of intercontinental HPAIV spread is through wild bird reservoirs, and
      wild birds were the likely sources of a Eurasian (EA) lineage HPAIV into North
      America in 2014. The introduction resulted in several reassortment events with
      North American (NA) lineage low-pathogenic avian influenza viruses and the
      reassortant EA/NA H5N2 went on to cause one of the largest HPAIV poultry
      outbreaks in North America. We evaluated three hypotheses about novel HPAIV
      introduced into wild and domestic bird hosts: (i) transmission of novel HPAIVs in
      wild birds was restricted by mechanisms associated with highly pathogenic
      phenotypes; (ii) the HPAIV poultry outbreak was not self-sustaining and required
      viral input from wild birds; and (iii) reassortment of the EA H5N8 generated
      reassortant EA/NA AIVs with a fitness advantage over fully Eurasian lineages in
      North American wild birds. We used a time-rooted phylodynamic model that
      explicitly incorporated viral population dynamics with evolutionary dynamics to
      estimate the basic reproductive number (R0) and viral migration among host types
      in domestic and wild birds, as well as between the EA H5N8 and EA/NA H5N2 in wild
      birds. We did not find evidence to support hypothesis (i) or (ii) as our
      estimates of the transmission parameters suggested that the HPAIV outbreak met or
      exceeded the threshold for persistence in wild birds (R0 > 1) and poultry (R0 ~
      1) with minimal estimated transmission among host types. There was also no
      evidence to support hypothesis (iii) because R0 values were similar among EA H5N8
      and EA/NA H5N2 in wild birds. Our results suggest that this novel HPAIV and
      reassortments did not encounter any transmission barriers sufficient to prevent
      persistence when introduced to wild or domestic birds.

PMID- 29636806
TI  - NT-proBNP: When is it useful in Obstetric Medicine?
AB  - Pregnancy, viewed as a stress test of the haemodynamic system, may unmask
      underlying cardiac disease. Pregnancy may also induce de novo cardiac disease. N
      terminal pro brain-type natriuretic peptide (NT-proBNP) is a useful biomarker in
      all clinical conditions in which the ventricle is stressed and especially
      stretched in the general population. In hypertensive diseases of pregnancy,
      increased levels of NT-proBNP in preeclampsia are associated with increased
      cardiac filling pressures and diastolic dysfunction. Increased levels of NT
      proBNP in pregnant women with known cardiac disease may lead to earlier diagnosis
      of impending heart failure. Similarly, elevated levels of NT-proBNP assist with
      the diagnosis of peripartum cardiomyopathy and are increasingly used in follow
      up. Women with known congenital heart disease who are pregnant can be screened
      for risk of cardiac events such as heart failure by the use of NT-proBNP levels.
      There is a paucity of data in pregnancy with the use of NT-proBNP and more
      research is needed.

PMID- 29636803
TI  - Challenges in dengue research: A computational perspective.
AB  - The dengue virus is now the most widespread arbovirus affecting human
      populations, causing significant economic and social impact in South America and
      South-East Asia. Increasing urbanization and globalization, coupled with
      insufficient resources for control, misguided policies or lack of political will,
      and expansion of its mosquito vectors are some of the reasons why interventions
      have so far failed to curb this major public health problem. Computational
      approaches have elucidated on dengue's population dynamics with the aim to
      provide not only a better understanding of the evolution and epidemiology of the
      virus but also robust intervention strategies. It is clear, however, that these
      have been insufficient to address key aspects of dengue's biology, many of which
      will play a crucial role for the success of future control programmes, including
      vaccination. Within a multiscale perspective on this biological system, with the
      aim of linking evolutionary, ecological and epidemiological thinking, as well as
      to expand on classic modelling assumptions, we here propose, discuss and
      exemplify a few major computational avenues-real-time computational analysis of
      genetic data, phylodynamic modelling frameworks, within-host model frameworks and
      GPU-accelerated computing. We argue that these emerging approaches should offer
      valuable research opportunities over the coming years, as previously applied and
      demonstrated in the context of other pathogens.

PMID- 29636808
TI  - Maternal and fetal outcomes of primary immune thrombocytopenia during pregnancy:
      A retrospective study.
AB  - Objective: We reviewed outcomes of 52 pregnancies in 45 women with immune
      thrombocytopenic purpura who delivered at Auckland Hospital with an antenatal
      platelet count of <100 * 109/L. Outcome measures: Primary outcomes were maternal
      platelet count at delivery and treatment response. Secondary outcomes included
      post-partum haemorrhage (PPH). Results: Most women had thrombocytopenia at
      delivery. Treatment with prednisone was given in 14 (27%) pregnancies with
      responses considered safe for delivery in 11 pregnancies (79%). Women in eight
      pregnancies also received intravenous immunoglobulin; in five pregnancies (63%) a
      platelet response acceptable for delivery was achieved.Seventeen pregnancies
      (33%) were complicated by a PPH >=500 mL. Ten pregnancies (19%) were complicated
      by a PPH >=1000 mL. PPH was reported in all women with a platelet count <50 *
      109/L at delivery. Conclusions: There were no antenatal bleeding complications
      but PPH was common among women with platelet counts <50 * 109/L at the time of
      birth.

PMID- 29636809
TI  - Follow-up and management of recurrent pregnancy losses due to massive perivillous
      fibrinoid deposition.
AB  - Massive perivillous fibrinoid deposition is a rare placental pathology associated
      with significant adverse pregnancy outcome and can recur. We provide a detailed
      case review of a woman through 10 of her pregnancies, including 8 consecutive
      pregnancy losses and 2 live births. We also conducted a retrospective chart
      review of all massive perivillous fibrinoid deposition placenta specimens at our
      institution over an eight-year period. A total of 42 cases of massive perivillous
      fibrinoid deposition were identified from 2007 to 2015, yielding an incidence of
      0.16%. Recurrence was seen in subsequent pregnancy in eight out of nine (88.9%)
      cases with more than one specimen. The clinical characteristics, perinatal
      outcomes and alpha-feto protein level of the 42 cases are presented. Also,
      presented is a review of the literature discussing placental pathology,
      pathogenetic mechanisms and management of this condition.

PMID- 29636807
TI  - Pregnancy in a woman with a Fontan circulation: A review.
AB  - More women with congenital heart disease survive to childbearing ages, due to
      improvements in surgical practice and postoperative care. This review discusses
      pregnancy in women with a single ventricle, describing maternal obstetric and
      cardiovascular complications and the increased risks of prematurity and adverse
      neonatal outcomes. Recommendations are made based on current understanding,
      guidelines and published literature, with recognition that there is much
      knowledge yet to be gained.

PMID- 29636810
TI  - Perinatal management of hepatitis B virus: Clinical implementation of updated
      Australasian management guidelines.
AB  - Objective: To evaluate the implementation of the 2013 Royal Australian and New
      Zealand College of Obstetricians and Gynaecologists 'Management of Hepatitis B in
      Pregnancy' guideline. Methods: Retrospective cohort study of the clinical
      management and obstetric outcomes among hepatitis B virus-positive women in a
      single tertiary maternity hospital. Women with viral load >200,000 IU/ml were
      referred to a specialised clinic for consideration of tenofovir disoproxil
      fumarate therapy to reduce mother to child transmission. Results: A total of
      11,496 women gave birth during the study period, of which 101 (0.9%) women were
      hepatitis B virus positive. Viral load was measured in 99 (98%) of 101 hepatitis
      B virus-positive women; 30 (30%) had a viral load >200,000 IU/ml. Twenty-six
      women accepted tenofovir disoproxil fumarate; of these, 23 had a successful
      virological response (viral load <200,000 IU/ml before delivery). Conclusions:
      Adherence to updated management guidelines and patient acceptance of tenofovir
      disoproxil fumarate in our Australian population were high when provided in the
      context of a dedicated perinatal service.

PMID- 29636811
TI  - Pregnancy-induced atypical haemolytic uremic syndrome: A new era with eculizumab.
AB  - Pregnancy is a well-recognised trigger of atypical haemolytic syndrome (P-aHUS)
      and often occurs in the post-partum period. Similar to atypical haemolytic uremic
      syndrome, it carries a poor prognosis with high morbidity particularly in the
      form of renal failure. Early recognition and intervention is crucial in its
      management particularly with the recent availability of eculizumab, a humanized
      monoclonal antibody to complement component C5, which has demonstrated drastic
      improvement in prognosis. The issue, however, is arriving at a timely diagnosis
      given the considerable amount of overlap in the clinical and biochemical
      manifestation of P-aHUS, HELLP syndrome (haemolysis, elevated liver enzyme and
      low platelet count) and other hypertensive disorders of pregnancy. We present a
      case report and literature review that highlights the clinical conundrum of
      arriving at the diagnosis. We also highlight the importance of early management
      of P-aHUS with eculizumab and its impact on improving morbidity.

PMID- 29636812
TI  - Sleep disordered breathing controlled by CPAP and sFlt-1 in a pregnant patient
      with chronic hypertension: Case report and literature review.
AB  - Background: There is recent interest exploring the possible impact of sleep
      disordered breathing on the mechanisms of preeclampsia. A biomarker of
      preeclampsia, soluble fms-like tyrosine kinase-1, has come to prominence in
      recent years. The aim of this study was to investigate the relationship between
      continuous positive airway pressure treatment, sleep disordered breathing and
      soluble fms-like tyrosine kinase-1 concentrations during pregnancy. Methods: A 38
      year-old G1P0 presented at 20 + 5 weeks. She had a history of chronic
      hypertension. Sleep studies revealed she had sleep disordered breathing with an
      AHI of 7.3/h. She was commenced on continuous positive airway pressure. Soluble
      fms-like tyrosine kinase-1 concentrations and blood pressure recordings were
      taken at various points during her pregnancy. Results: She did not develop
      preeclampsia or require an escalation in her antihypertensives. Soluble fms-like
      tyrosine kinase-1 concentrations rose 16% from a low baseline. She remained
      compliant with her continuous positive airway pressure. She progressed to birth a
      well, live, term baby. Conclusion: Continuous positive airway pressure treatment
      controlled sleep disordered breathing in a high risk pregnant woman with chronic
      hypertension with no increase in soluble fms-like tyrosine kinase-1
      concentrations.

PMID- 29636813
TI  - Refractory severe immune thrombocytopenia in a twin pregnancy.
AB  - A 34-year-old woman presented at 29 weeks gestation of a twin pregnancy, with a
      platelet count of 1 * 109/l. She was extensively investigated and was
      subsequently diagnosed with severe immune thrombocytopenia. She did not respond
      to initial treatment with corticosteroids and intravenous immunoglobulin. She
      also failed to respond to second-line therapies of Anti-D immunoglobulin,
      Azathioprine and the thrombopoietin agonist Romiplostim. Her case was further
      complicated by an episode of obstetric cholestasis possibly related to
      Azathioprine treatment. She went on to require plasma exchange around the time of
      an elective Caesarean section which provided temporary improvement in the
      platelet count and enabled safe delivery. This case highlights some of the
      challenges faced in the management of patients with severe and refractory immune
      thrombocytopenia during pregnancy.

PMID- 29636814
TI  - Group B Streptococcus tricuspid valve endocarditis with subsequent septic
      embolization to the pulmonary artery: A case report following elective abortion.
AB  - Background: Tricuspid valve endocarditis caused by Group B streptococcus is a
      rare clinical entity with poor prognosis and has been previously reported
      following gynecologic procedures. Case summary: We report a case of an 18-year
      old female diagnosed with Group B streptococcus tricuspid valve endocarditis with
      septic emboli following an elective therapeutic abortion. After six weeks of
      treatment with ceftriaxone, she returned with recurrent symptoms and was found to
      have embolized a sizable vegetation to the pulmonary artery with probable lung
      infarction. She underwent surgical embolectomy and was treated with antibiotics
      and anticoagulation and was subsequently discharged in stable condition.
      Conclusion: Group B streptococcus endocarditis is a serious complication of
      gynecologic procedures. The role of preoperative antibiotics, postoperative
      clinical suspicion of endocarditis based on respiratory symptoms and a
      multidisciplinary approach may lead to enhanced patient outcomes.

PMID- 29636815
TI  - The use of PET/CT in pregnancy: A case report of malignant parathyroid carcinoma
      and a review of the literature.
AB  - Positron emission tomography scanning is not commonly performed in pregnancy but
      can be done if required. Fetal doses of radiation can be minimized, and our case
      exemplifies the safe application of positron emission tomography/computed
      tomography in pregnancy. A 38-year-old woman in her first ongoing pregnancy
      presented at 28 weeks' gestation with symptomatic hypercalcemia. Given a history
      of parathyroid carcinoma, recurrence was suspected. Ultrasound and magnetic
      resonance imaging failed to locate the lesion. However, positron emission
      tomography/computed tomography identified a culprit supraclavicular lymph node.
      This was excised under local anesthesia resulting in normalization of parathyroid
      hormone and calcium levels. A term, healthy baby was delivered. The literature
      provides support that the use of positron emission tomography/computed tomography
      is acceptable when indicated, and there are modifications to protocols that can
      further limit risk.

PMID- 29636817
TI  - Metabolic engineering of Corynebacterium glutamicum for efficient production of
      succinate from lignocellulosic hydrolysate.
AB  - Background: Succinate has been recognized as one of the most important bio-based
      building block chemicals due to its numerous potential applications. However,
      efficient methods for the production of succinate from lignocellulosic feedstock
      were rarely reported. Nevertheless, Corynebacterium glutamicum was engineered to
      efficiently produce succinate from glucose in our previous study. Results: In
      this work, C. glutamicum was engineered for efficient succinate production from
      lignocellulosic hydrolysate. First, xylose utilization of C. glutamicum was
      optimized by heterologous expression of xylA and xylB genes from different
      sources. Next, xylA and xylB from Xanthomonas campestris were selected among four
      candidates to accelerate xylose consumption and cell growth. Subsequently, the
      optimal xylA and xylB were co-expressed in C. glutamicum strain SAZ3
      (DeltaldhADeltaptaDeltapqoDeltacatPsod-ppcPsod-pyc) along with genes encoding
      pyruvate carboxylase, citrate synthase, and a succinate exporter to achieve
      succinate production from xylose in a two-stage fermentation process. Xylose
      utilization and succinate production were further improved by overexpressing the
      endogenous tkt and tal genes and introducing araE from Bacillus subtilis. The
      final strain C. glutamicum CGS5 showed an excellent ability to produce succinate
      in two-stage fermentations by co-utilizing a glucose-xylose mixture under
      anaerobic conditions. A succinate titer of 98.6 g L-1 was produced from corn
      stalk hydrolysate with a yield of 0.87 g/g total substrates and a productivity of
      4.29 g L-1 h-1 during the anaerobic stage. Conclusion: This work introduces an
      efficient process for the bioconversion of biomass into succinate using a
      thoroughly engineered strain of C. glutamicum. To the best of our knowledge, this
      is the highest titer of succinate produced from non-food lignocellulosic
      feedstock, which highlights that the biosafety level 1 microorganism C.
      glutamicum is a promising platform for the envisioned lignocellulosic
      biorefinery.

PMID- 29636818
TI  - Functional characterization of the upstream components of the Hog1-like kinase
      cascade in hyperosmotic and carbon sensing in Trichoderma reesei.
AB  - Background: Trichoderma reesei holds a high capacity for protein secretion and
      represents the most important cellulase producer in industry. However, the
      external signal sensing and intracellular signal transduction during cellulose
      induction remain unclear. As one of the most pervasive signal transduction
      pathways in all eukaryotic species, the mitogen-activated protein kinase (MAPK)
      pathway and its upstream sensing and signaling components are involved in various
      physiological processes including stress and nutrient sensing. Particularly, the
      Hog1-type MAPK Tmk3 has been reported to be involved in the cellulase production
      in T. reesei. Results: Here we established the physiological role of two upstream
      regulatory branches, the Sho1 branch and the Sln1 branch, of the Hog1-type Tmk3
      pathway in T. reesei. Deletion of Trste20 of the Sho1 branch or repression of
      Trypd1 of the Sln1 branch reduced the resistance to high salt stress, whereas
      TrSho1 showed an opposing effect to that of TrSte20 and the identified TrSln1
      seemed to be dispensable in the osmotic regulation. The Sho1 and Sln1 branches
      also participated in the cell wall integrity maintenance and other stress
      responses (i.e. oxidative and thermo stresses). Notably, TrSho1 and TrSte20 of
      the Sho1 branch and TrYpd1 of the Sln1 branch were shown to be differentially
      involved in the cellulase production of T. reesei. Repression of Trypd1 hardly
      affected cellulase induction, whereas overexpression of Trypd1 resulted in the
      reduced production of cellulases. Contrary to the case of Trypd1, repression of
      Trsho1 or deletion of Trste20 significantly reduced the transcription of
      cellulase genes. Conclusions: TrSho1 and TrSte20 of the Sho1 branch and TrYpd1 of
      the Sln1 branch are all involved in general stress responses including
      hyperosmotic regulation and cell wall integrity maintenance. Moreover, our study
      revealed that the Sho1 and Sln1 osmosensing pathways are differentially involved
      in the regulation of cellulase production in T. reesei. The Sho1 branch
      positively regulated the production of cellulases and the transcription of
      cellulase genes while TrYpd1 of the Sln1 branch negatively controlled the
      cellulase production, supporting the crosstalks of osmosensing and nutrient
      sensing.

PMID- 29636819
TI  - Cultivation of lipid-producing microalgae in struvite-precipitated liquid
      digestate for biodiesel production.
AB  - Background: Using liquid digestate from the biogas industry as a medium to
      culture lipid-producing microalgae is considered mutually beneficial for
      digestate valorization and for reducing the cost of microalgal cultivation.
      However, the low transmittance and high ammonium (NH4+-N) levels in liquid
      digestate negatively influence microalgae growth. Results: Struvite precipitation
      was used to pretreat liquid digestate. To obtain struvite-precipitated
      supernatant with an ideal transmittance, NH4+-N concentration, salinity, and N:P
      ratio for microalgal growth, there should be a 1:1.2:1.2 NH4+:Mg2+:PO43- molar
      ratio in the liquid digestate, with KH2PO4 and MgCl2 added through continuous
      stirring. The addition and stirring was subsequently stopped when the pH reached
      8.5. Of the nine tested microalgae species, Dictyosphaerium ehrenbergianum
      exhibited the best growth in the supernatant. The biomass productivity and lipid
      content of D. ehrenbergianum cultured in the struvite-precipitated supernatant
      were 161.06 mg/l/days and 34.33%, respectively, which was higher than when
      cultured in the standard BG-11 medium. Moreover, the struvite-precipitated
      supernatant improved the accumulation of monounsaturated fatty acids and
      saturated fatty acids. Conclusions: This study described a new way to combine
      liquid digestate treatment and microalgal biodiesel production. The struvite
      pretreated liquid digestate can be used to culture D. ehrenbergianum for
      biodiesel production.

PMID- 29636820
TI  - Pelagibaca bermudensis promotes biofuel competence of Tetraselmis striata in a
      broad range of abiotic stressors: dynamics of quorum-sensing precursors and
      strategic improvement in lipid productivity.
AB  - Background: Amelioration of biofuel feedstock of microalgae using sustainable
      means through synthetic ecology is a promising strategy. The co-cultivation model
      (Tetraselmis striata and Pelagibaca bermudensis) was evaluated for the robust
      biofuel production under varying stressors as well as with the selected two-stage
      cultivation modes. In addition, the role of metabolic exudates including the
      quorum-sensing precursors was assessed. Results: The co-cultivation model
      innovated in this study supported the biomass production of T. striata in a
      saline/marine medium at a broad range of pH, salinity, and temperature/light
      conditions, as well as nutrient limitation with a growth promotion of 1.2-3.6
      fold. Hence, this developed model could contribute to abiotic stress mitigation
      of T. striata. The quorum-sensing precursor dynamics of the growth promoting
      bacteria P. bermudensis exhibited unique pattern under varying stressors as
      revealed through targeted metabolomics (using liquid chromatography-mass
      spectrometry, LC-MS). P. bermudensis and its metabolic exudates mutually promoted
      the growth of T. striata, which elevated the lipid productivity. Interestingly,
      hydroxy alkyl quinolones independently showed growth inhibition of T. striata on
      elevated concentration. Among two-stage cultivation modes (low pH, elevated
      salinity, and nitrate limitation), specifically, nitrate limitation induced a 1.5
      times higher lipid content (30-31%) than control in both axenic and co-cultivated
      conditions. Conclusion: Pelagibaca bermudensis is established as a potential
      growth promoting native phycospheric bacteria for robust biomass generation of T.
      striata in varying environment, and two-stage cultivation using nitrate
      limitation strategically maximized the biofuel precursors for both axenic and co
      cultivation conditions (T and T-PB, respectively). Optimum metabolic exudate of
      P. bermudensis which act as a growth substrate to T. striata surpasses the
      antagonistic effect of excessive hydroxy alkyl quinolones [HHQ, 4-hydroxy-2
      alkylquinolines and PQS (pseudomonas quorum signal), 2-heptyl-3-hydroxy-4(1H)
      quinolone].

PMID- 29636821
TI  - Engineering and application of synthetic nar promoter for fine-tuning the
      expression of metabolic pathway genes in Escherichia coli.
AB  - Background: Promoters regulate the expression of metabolic pathway genes to
      control the flux of metabolism. Therefore, fine-tuning of metabolic pathway gene
      expression requires an applicable promoter system. In this study, a dissolved
      oxygen-dependent nar promoter was engineered for fine-tuning the expression
      levels of biosynthetic pathway enzymes in Escherichia coli. To demonstrate the
      feasibility of using the synthetic nar promoters in production of biochemicals in
      E. coli, the d-lactate pathway consisting of one enzyme and the 2,3-butanediol
      (BDO) pathway consisting of three enzymes were investigated. Results: The spacer
      sequence of 15 bp between the - 35 and - 10 elements of the upstream region of
      the wild-type nar promoter was randomized, fused to the GFP gene, transduced into
      E. coli, and screened by flow cytometry. The sorted synthetic nar promoters were
      divided into three groups according to fluorescence intensity levels: strong,
      intermediate, and weak. The selected three representative nar promoters of
      strong, intermediate, and weak intensities were used to control the expression
      level of the d-lactate and 2,3-BDO biosynthetic pathway enzymes in E. coli. When
      the ldhD gene encoding d-lactate dehydrogenase was expressed under the control of
      the strong synthetic nar promoter in fed-batch cultures of E. coli, the d-lactate
      titers were 105.6 g/L, 34% higher than those using the wild-type promoter (79.0
      g/L). When the three 2,3-BDO pathway genes (ilvBN, aldB, and bdh1) were expressed
      under the control of combinational synthetic nar promoters (strong-weak-strong)
      in fed-batch cultures of E. coli, the titers of 2,3-BDO were 88.0 g/L, 72% higher
      than those using the wild-type promoter (51.1 g/L). Conclusions: The synthetic
      nar promoters, which were engineered to have strong, intermediate, and weak
      intensities, were successfully applied to metabolic engineering of d-lactate and
      2,3-BDO pathways in E. coli. By controlling expression levels of d-lactate and
      2,3-BDO pathway enzymes using the synthetic nar promoters, the production of d
      lactate and 2,3-BDO was increased over that using the wild-type promoter by 34
      and 72%, respectively. Thus, this synthetic promoter module system will support
      the improved production of biochemicals and biofuels through fine-tuning of gene
      expression levels.

PMID- 29636822
TI  - Maternal interchromosomal insertional translocation leading to 1q43-q44 deletion
      and duplication in two siblings.
AB  - Background: 1q43-q44 deletion syndrome is a well-defined chromosomal disorder
      which is characterized by moderate to severe mental retardation, and variable but
      characteristic facial features determined by the size of the segment and the
      number of genes involved. However, patients with 1q43-q44 duplication with a
      clinical phenotype comparable to that of 1q43-q44 deletion are rarely reported.
      Moreover, pure 1q43-q44 deletions and duplications derived from balanced
      insertional translocation within the same family with precisely identified
      breakpoints have not been reported. Case presentation: The proband is a 6-year
      old girl with profound developmental delay, mental retardation, microcephaly,
      epilepsy, agenesis of the corpus callosum and hearing impairment. Her younger
      brother is a 3-month-old boy with macrocephaly and mild developmental delay in
      gross motor functions. G-banding analysis of the subjects at the 400-band level
      did not reveal any subtle structural changes in their karyotypes. However, single
      nucleotide polymorphism (SNP) array analysis showed a deletion and a duplication
      of approximately 6.0 Mb at 1q43-q44 in the proband and her younger brother,
      respectively. The Levicare analysis pipeline of whole-genome sequencing (WGS)
      further demonstrated that a segment of 1q43-q44 was inserted at 14q23.1 in the
      unaffected mother, which indicated that the mother was a carrier of a
      46,XX,ins(14;1)(q23.1;q43q44) insertional translocation. Moreover, Sanger
      sequencing was used to assist the mapping of the breakpoints and the final
      validation of those breakpoints. The breakpoint on chromosome 1 disrupted the
      EFCAB2 gene in the first intron, and the breakpoint on chromosome 14 disrupted
      the PRKCH gene within the 12th intron. In addition, fluorescence in situ
      hybridization (FISH) further confirmed that the unaffected older sister of the
      proband carried the same karyotype as the mother. Conclusion: Here, we describe a
      rare family exhibiting pure 1q43-q44 deletion and duplication in two siblings
      caused by a maternal balanced insertional translocation. Our study demonstrates
      that WGS with a carefully designed analysis pipeline is a powerful tool for
      identifying cryptic genomic balanced translocations and mapping the breakpoints
      at the nucleotide level and could be an effective method for explaining the
      relationship between karyotype and phenotype.

PMID- 29636823
TI  - People with diabetes foot complications do not recall their foot education: a
      cohort study.
AB  - Background: The purpose of this study is to document what and how diabetes
      specific foot health information was provided during a podiatry consultation, and
      what information was retained at 1 month post consultation. Methods: This project
      was embedded within a prospective cohort study with two groups, podiatrists and
      people with diabetes. Data collection included the Problem Areas in Diabetes
      Questionnaire (PAID), Montreal Cognitive Assessment (MoCA), information covered
      during the consultation, method of delivery and perceived key educational message
      from both participant perspectives at the time of the appointment and 1 month
      post appointment. Results: There were three podiatrists and 24 people with
      diabetes who provided information at the two time points. Diabetes education
      provided by the podiatrists was mostly verbal. The key educational message
      recalled by both groups differed at the time of the appointment (14 out of 24 of
      responses) and at 1 month post the appointment time (11 out of 24 of responses).
      Conclusions: Education is a vital component to the treatment regime of people
      with diabetes. It appears current approaches are ineffective in enhancing
      understanding of diabetes impact on foot health. This study highlights the need
      for research investigating better ways to deliver key pieces of information to
      this population.

PMID- 29636824
TI  - The prevalence of Helicobacter pylori infection and other risk factors among
      Mongolian dyspeptic patients who have a high incidence and mortality rate of
      gastric cancer.
AB  - Background: Mongolia has not only the second highest incidence rate but also the
      highest mortality rate for gastric cancer globally. In addition to gastric
      cancer, ulcerative disease complications are also life threatening; thus,
      investigating Helicobacter pylori infection and other risk factors is essential.
      Results: H.pylori infection was high in tested dyspeptic patients from all parts
      of Mongolia, with an overall infection rate of 80.0%. Logistic regression
      analysis showed that H. pylori infection was associated with gastritis (odds
      ratio; 9.0 ([95% confidence interval 5.0-16.2]); p < 0.0001). H. pylori infection
      (3.3 [2.0-5.4]; p < 0.0001) and > 40 years old (1.5 [1.0-2.0]; p < 0.02) were
      both associated with atrophy. However, > 40 years old (3.8 [2.4-6.0]; p < 0.0001)
      and high salt intakes (1.6 [1.0-2.3]; p < 0.02), but not H. pylori infection,
      were associated with intestinal metaplasia. Excessive amount of salt usage was
      dramatically higher in northern and western parts of Mongolia, where precancerous
      diseases, such as erosive esophagitis (for cardia cancer), severe atrophy, and
      intestinal metaplasia (for non-cardia cancer), were highly prevalent.
      Conclusions: H. pylori infection was the major gastric health problem among the
      Mongolian population. In addition, environmental factors such as high salt intake
      worsened the clinical outcome. Therefore, a nationwide screening and eradication
      of H. pylori infection as well as salt-reducing measures should be implemented.

PMID- 29636825
TI  - Combination of basal insulin and GLP-1 receptor agonist: is this the end of basal
      insulin alone in the treatment of type 2 diabetes?
AB  - Glycemic control has been considered a major therapeutic goal within the scope of
      diabetes management, as supported by robust observational and experimental
      evidence. However, the coexistence of micro and macrovascular disease is
      associated with the highest cardiovascular risks which highlights the importance
      that pharmacological treatment of type 2 diabetes mellitus provides not only
      glycemic control, but also cardiovascular safety. Basal insulin is a highly
      effective treatment in reducing fasting blood glucose, but it is associated with
      considerable risk of hypoglycemia and weight gain. Glucagon like peptide 1
      receptor agonists (GLP-1 RAs) are also effective in terms of glycemic control and
      associated with weight loss and low risk of hypoglycemia. The potential benefits
      of combining GLP-1RAs with basal insulin are contemplated in the current position
      statement of several different position statement and guidelines. This article
      reviews the efficacy and safety of different strategies to initiate and intensify
      basal insulin, with focus on new fixed ratio combinations of basal insulin with
      GLP-1 RAs available for use in a single injection pen (insulin
      degludec/liraglutide and insulin glargine/lixisenatide).

PMID- 29636826
TI  - STAT3 as a potential immunotherapy biomarker in oncogene-addicted non-small cell
      lung cancer.
AB  - Immune checkpoint blockade has modified the treatment landscape for many types of
      tumors, including lung cancer. Still our knowledge on the biology of the
      interaction between tumor cells and the microenvironment is limited, preventing
      the optimal use of these new compounds and the maximum benefit that the patients
      can derive from them. We have actively worked on the role of STAT3, a
      transcriptional factor that causes innate resistance to targeted therapies in
      oncogene-addicted tumors. In this short review we take the opportunity to express
      our opinion and review existing knowledge on the immune role of STAT3 and the
      possible implications that this may have for the discovery of new biomarkers to
      predict response to immunotherapy, as well as new partners to combine with and
      increase the efficacy of immune checkpoint inhibitors.

PMID- 29636827
TI  - Estrogenicity of essential oils is not required to relieve symptoms of urogenital
      atrophy in breast cancer survivors.
AB  - Background: Urogenital atrophy (UA) is a common treatment-limiting side effect of
      endocrine therapies. Topical estrogen is effective but systemic absorption may
      counter aromatase inhibitor efficacy. Numerous complementary approaches are
      marketed for use in UA without rigorous testing of their estrogenicity. We tested
      multiple essential oils in cancer cell growth and estrogen reporter assays in
      vitro and assessed clinical outcomes with the essential oil pessaries (EOPs) in
      breast cancer survivors with UA. Methods: Effects on cell growth were tested in
      hormone-dependent (MCF-7) and -independent (MDA-MB-231) cell lines using the
      sulforhodamine-B assay. An estrogen response element (ERE) luciferase reporter
      assay was used to assess estrogenicity directly. Antifungal activity against two
      common pathogenic yeasts was assessed using standard microdilution methods. EOPs
      were offered to breast cancer survivors with symptomatic UA and the service
      evaluated using serial questionnaires. Results: Two essential oils, Cymbopogon
      martinii and Pelargonium graveolens, demonstrated marked estrogenicity,
      stimulating ER+ cell growth and ERE-luciferase reporter activity to levels seen
      with premenopausal estradiol concentrations. Additional oils were screened for
      estrogenicity and Lavandula angustifolia and Chamaemelum nobile identified as
      non/minimally estrogenic. The antifungal activity of this combination of oils was
      confirmed. A second cohort of breast cancer survivors with UA received the second
      generation EOP with comparable improvement in symptom scores suggesting that
      estrogenicity may not be required for optimal therapy of UA. Conclusion: Certain
      essential oils demonstrate profound estrogenicity and caution should be exercised
      before their use in breast cancer survivors. Our minimally estrogenic pessary
      will be formally tested in clinical trials.

PMID- 29636829
TI  - Contrast-induced encephalopathy after coronary angioplasty in a patient with ST
      elevation myocardial infarction.

PMID- 29636828
TI  - Prognostic value of soluble ST2 postaortic valve replacement: a meta-analysis.
AB  - Objectives: Soluble suppression of tumorigenicity 2 (sST2) is a member of the
      interleukin-1 receptor family and a modulator of hypertrophic and fibrotic
      responses. Its prognostic value for patients undergoing aortic valve replacement
      (AVR) has been examined in prospective studies but to date, there has been no
      systematic evaluation or meta-analysis on this issue. Methods: PubMed and Embase
      were searched until 1 October 2017 for studies that evaluated the relationship
      between sST2 levels and mortality after AVR. Results: A total of 18 and 37
      entries were retrieved from both databases, from which four studies were included
      in the final meta-analysis. In a total of 1154 subjects (50% male, mean age 80+/
      10 years old, mean follow-up 14 months), elevated sST2 levels were significantly
      associated with a 44% increase in the risk of all-cause mortality (HR 1.44, 95%
      CI 1.30 to 1.60, p<0.0001; I2: 44%). Conclusions: sST2 significantly predicts all
      cause mortality in patients who have undergone AVR, but this conclusion is
      limited by the small number of patients. Larger prospective studies are required
      to better elucidate its value for risk stratification in this patient population.

PMID- 29636830
TI  - Dilated superior vena cava in fetal echocardiographic three-vessel view: what
      lies ahead?
AB  - : A 38-year-old woman, 37+3 weeker was incidentally detected to have fetal
      cardiomegaly during 36 weeks ultrasound and referred for fetal echocardiogram.
      Antenatal history and anomaly scan were normal. Fetal echocardiogram showed heart
      rate of 153/min, sinus rhythm, situs solitus, levocardia, dilated right atrium
      and ventricle with venoatrial, atrioventricular and ventriculoarterial
      concordances. All cardiac valves were normal; cardiac crux was intact with
      separate mitral and tricuspid annuli (figure 1A-C and online supplementary video
      1). Mild tricuspid regurgitation with peak velocity of 1.77 m/s was noted. There
      was no evidence of Ebstein's anomaly. Interventricular septum was intact.
      Pulmonary veins were seen entering left atrium (LA) without a retrocardiac
      chamber. Both aortic and ductal arches were adequate but with significant flow
      reversal visualised in descending aorta. Three-vessel view showed dilated right
      superior vena cava (SVC) with normal spatial arrangement and sizes of aorta and
      pulmonary artery. Patent foramen ovale and patent ductus arteriosus were shunting
      normally. Inferior vena cava (IVC), hepatic and portal veins were normal.
      Significant hepatomegaly was seen without any evidence of hydrops.
      10.1136/heartasia-2018-010998.supp1Supplementary data Figure 1(A) Fetal
      echocardiogram showing atrioventricular concordance with right atrium (RA)
      connected to morphological right ventricle and left atrium (LA) connected to
      morphological left ventricle (LV). Blue arrow depicts a large foramen ovale
      shunting from RA to LA. There is no retrocardiac chamber behind LA. (B) Three
      vessel view in fetal echocardiogram showing normal right to left arrangement of
      superior vena cava (SVC), aorta (Ao) and pulmonary artery (PA). Interestingly,
      SVC is bigger than its neighbours which is against the norm. (C) Fetal short-axis
      echocardiographic view showing situs solitus with normal arrangement of RA and
      LA. RA is draining into right ventricle which is draining through PA into the
      ductal arch. However, significant aortic run-off is noted in aorta. Question: As
      per the available echocardiographic data, what is the most likely diagnosis for
      fetal heart failure?Idiopathic dilatation of SVC?Supracardiac total anomalous
      pulmonary venous connection?Fetal vein of Galen malformation?Fetal anaemia?

PMID- 29636831
TI  - Investigation of a potential HCHO measurement artifact from ISOPOOH.
AB  - Recent laboratory experiments have shown that a first generation isoprene
      oxidation product, ISOPOOH, can decompose to methyl vinyl ketone (MVK) and
      methacrolein (MACR) on instrument surfaces, leading to overestimates of MVK and
      MACR concentrations. Formaldehyde (HCHO) was suggested as a decomposition co
      product, raising concern that in situ HCHO measurements may also be affected by
      an ISOPOOH interference. The HCHO measurement artifact from ISOPOOH for the NASA
      In Situ Airborne Formaldehyde instrument (ISAF) was investigated for the two
      major ISOPOOH isomers, (1,2)-ISOPOOH and (4,3)-ISOPOOH, under dry and humid
      conditions. The dry conversion of ISOPOOH to HCHO was 3+/-2% and 6+/-4% for (1,2)
      ISOPOOH and (4,3)-ISOPOOH, respectively. Under humid (RH= 40-60%) conditions,
      conversion to HCHO was 6+/-4% for (1,2)-ISOPOOH and 10+/-5% for (4,3)-ISOPOOH.
      The measurement artifact caused by conversion of ISOPOOH to HCHO in the ISAF
      instrument was estimated for data obtained on the 2013 September 6 flight of the
      Studies of Emissions and Atmospheric Composition, Clouds and Climate Coupling by
      Regional Surveys (SEAC4RS) campaign. Prompt ISOPOOH conversion to HCHO was the
      source for <4% of the observed HCHO, including in the high-isoprene boundary
      layer. Time-delayed conversion, where previous exposure to ISOPOOH affects
      measured HCHO later in flight, was conservatively estimated to be < 10% of
      observed HCHO and is significant only when high ISOPOOH sampling periods
      immediately precede periods of low HCHO.

PMID- 29636832
TI  - Methylated genomic loci encoding microRNA as a biomarker panel in tissue and
      saliva for head and neck squamous cell carcinoma.
AB  - Background: To identify aberrant promoter methylation of genomic loci encoding
      microRNA (mgmiR) in head and neck squamous cell carcinoma (HNSCC) and to evaluate
      a biomarker panel of mgmiRs to improve the diagnostic accuracy of HNSCC in
      tissues and saliva. Methods: Methylation of promoter regions of mgmiR candidates
      was initially screened using HNSCC and control cell lines and further selected
      using HNSCC and control tissues by quantitative methylation-specific PCR (qMS
      PCR). We then examined a panel of seven mgmiRs for validation in an expanded
      cohort including 189 HNSCC and 92 non-HNSCC controls. Saliva from 86 pre
      treatment HNSCC patients and 108 non-HNSCC controls was also examined using this
      panel of seven mgmiRs to assess the potentials of clinical utilization. Results:
      Among the 315 screened mgmiRs, 12 mgmiRs were significantly increased in HNSCC
      cell lines compared to control cell lines. Seven out of the 12 mgmiRs, i.e.,
      mgmiR9-1, mgmiR124-1, mgmiR124-2, mgmiR124-3, mgmiR129-2, mgmiR137, and
      mgmiR148a, were further found to significantly increase in HNSCC tumor tissues
      compared to control tissues. Using multivariable logistic regression with
      dichotomized variables, a combination of the seven mgmiRs had sensitivity and
      specificity of 92.6 and 92.4% in tissues and 76.7 and 86.1% in saliva,
      respectively. Area under the receiver operating curve for this panel was 0.97 in
      tissue and 0.93 in saliva. This model was validated by independent bootstrap
      validation and random forest analysis. Conclusions: mgmiR biomarkers represent a
      novel and promising screening tool, and the seven-mgmiR panel is able to robustly
      detect HNSCC in both patient tissue and saliva.

PMID- 29636834
TI  - Allele-specific methylation in the FADS genomic region in DNA from human saliva,
      CD4+ cells, and total leukocytes.
AB  - Background: Genetic variants within the fatty acid desaturase (FADS) gene cluster
      (human Chr11) are important regulators of long-chain (LC) polyunsaturated fatty
      acid (PUFA) biosynthesis in the liver and consequently have been associated with
      circulating LC-PUFA levels. More recently, epigenetic modifications such as DNA
      methylation, particularly within the FADS cluster, have been shown to affect LC
      PUFA levels. Our lab previously demonstrated strong associations of allele
      specific methylation (ASM) between a single nucleotide polymorphism (SNP)
      rs174537 and CpG sites across the FADS region in human liver tissues. Given that
      epigenetic signatures are tissue-specific, we aimed to evaluate the methylation
      status and ASM associations between rs174537 and DNA methylation obtained from
      human saliva, CD4+ cells and total leukocytes derived from whole blood. The goals
      were to (1) determine if DNA methylation from these peripheral samples would
      display similar ASM trends as previously observed in human liver tissues and (2)
      evaluate the associations between DNA methylation and circulating LC-PUFAs.
      Results: DNA methylation at six CpG sites spanning FADS1 and FADS2 promoter
      regions and a putative FADS enhancer region were determined in two Caucasian
      cohorts of healthy volunteers: leukocytes in cohort 1 (n = 89, median age = 43,
      35% male) and saliva and CD4+ cells in cohort 2 (n = 32, median age = 41, 41%
      male). Significant ASM between rs174537 and DNA methylation at three CpG sites
      located in the FADS2 promoter region (i.e., chr11:61594865, chr11:61594876,
      chr11:61594907) and one CpG site in the putative enhancer region (chr11:61587979)
      were observed with leukocytes. In CD4+ cells, significant ASM was observed at CpG
      sites chr11:61594876 and chr11:61584894. Genotype at rs174537 was significantly
      associated with DNA methylation from leukocytes. Similar trends were observed
      with CD4+ cells, but not with saliva. DNA methylation from leukocytes and CD4+
      cells also significantly correlated with circulating omega-6 LC-PUFAs.
      Conclusions: We observed significant ASM between rs174537 and DNA methylation at
      key regulatory regions in the FADS region from leukocyte and CD4+ cells. DNA
      methylation from leukocytes also correlated with circulating omega-6 LC-PUFAs.
      These results support the use of peripheral whole blood samples, with leukocytes
      showing the most promise for future nutrigenomic studies evaluating epigenetic
      modifications affecting LC-PUFA biosynthesis in humans.

PMID- 29636833
TI  - Epigenetics in Turner syndrome.
AB  - Background: Monosomy of the X chromosome is the most frequent genetic abnormality
      in human as it is present in approximately 2% of all conceptions, although 99% of
      these embryos are spontaneously miscarried. In postnatal life, clinical features
      of Turner syndrome may include typical dysmorphic stigmata, short stature, sexual
      infantilism, and renal, cardiac, skeletal, endocrine and metabolic abnormalities.
      Main text: Turner syndrome is due to a partial or total loss of the second sexual
      chromosome, resulting in the development of highly variable clinical features.
      This phenotype may not merely be due to genomic imbalance from deleted genes but
      may also result from additive influences on associated genes within a given gene
      network, with an altered regulation of gene expression triggered by the absence
      of the second sex chromosome. Current studies in human and mouse models have
      demonstrated that this chromosomal abnormality leads to epigenetic changes,
      including differential DNA methylation in specific groups of downstream target
      genes in pathways associated with several clinical and metabolic features, mostly
      on autosomal chromosomes. In this article, we begin exploring the potential
      involvement of both genetic and epigenetic factors in the origin of X chromosome
      monosomy. We review the dispute between the meiotic and post-zygotic origins of
      45,X monosomy, by mainly analyzing the findings from several studies that compare
      gene expression of the 45,X monosomy to their euploid and/or 47,XXX trisomic cell
      counterparts on peripheral blood mononuclear cells, amniotic fluid, human
      fibroblast cells, and induced pluripotent human cell lines. From these studies, a
      profile of epigenetic changes seems to emerge in response to chromosomal
      imbalance. An interesting finding of all these studies is that methylation-based
      and expression-based pathway analyses are complementary, rather than overlapping,
      and are correlated with the clinical picture displayed by TS subjects.
      Conclusions: The clarification of these possible causal pathways may have future
      implications in increasing the life expectancy of these patients and may provide
      informative targets for early pharmaceutical intervention.

PMID- 29636835
TI  - PKM2 Is Required to Activate Myeloid Dendritic Cells from Patients with Severe
      Aplastic Anemia.
AB  - Severe aplastic anemia (SAA) is an autoimmune disease in which bone marrow
      failure is mediated by activated myeloid dendritic cells (mDCs) and T
      lymphocytes. Recent research has identified a strong immunomodulatory effect of
      pyruvate kinase M2 (PKM2) on dendritic cells in immune-mediated diseases. In this
      study, we aimed to explore the role of PKM2 in the activation of mDCs in SAA. We
      observed conspicuously higher levels of PKM2 in mDCs from SAA patients compared
      to normal controls at both the gene and protein levels. Concurrently, we
      unexpectedly discovered that after the mDC-specific downregulation of PKM2, mDCs
      from patients with SAA exhibited weakened phagocytic activity and significantly
      decreased and shortened dendrites relative to their counterparts from normal
      controls. The expression levels of the costimulatory molecules CD86 and CD80 were
      also reduced on mDCs. Our results also suggested that PKM2 knockdown in mDCs
      reduced the abilities of these cells to promote the activation of CD8+ T cells
      (CTLs), leading to the decreased secretion of cytotoxic factors by the latter
      cell type. These findings demonstrate that mDC activation requires an elevated
      intrinsic PKM2 level and that PKM2 improves the immune status of patients with
      SAA by enhancing the functions of mDCs and, consequently, CTLs.

PMID- 29636837
TI  - Nephroprotective Effect of Zingerone against CCl4-Induced Renal Toxicity in Swiss
      Albino Mice: Molecular Mechanism.
AB  - The protective effects of Zingerone against CCl4 induced nephrotoxicity in Swiss
      albino mice via modulation of metabolizing enzyme, oxidative stress, inflammatory
      cytokines, and apoptosis. The biochemical estimation indicated that the BUN and
      creatinine were significantly increased in group 2 (CCl4) compared to group 1
      (normal) which was significantly reduced after treatment with Zingerone in group
      3 when compared with group 2. The CCl4 treatment has significantly increased
      TBARS levels and reduced the antioxidant enzyme such as GSH, GPx, GR, GST, CAT,
      and SOD in group 2 compared to group 1, while the Zingerone treatment showed
      significant reduction in TBARS levels and increased the antioxidant enzymes in
      group 3 (CCl4 + Zingerone) as compared to group 2. Similarly, it was observed
      that CCl4 significantly increased the cytokines such as IL-1beta, IL-2, and
      TNFalpha levels in group 2 as compared to group 1. The treatment with Zingerone
      significantly attenuated the levels of IL-1beta, IL-2, and TNFalpha in group 3
      compared to group 2. Caspase 3 and caspase 9 were also significantly increased in
      CCl4-treated group 2, whereas Zingerone treatment significantly reduced the
      elevated levels of caspases 3 and 9 in group 3 compared to group 2.

PMID- 29636838
TI  - Polydatin Protects Diabetic Heart against Ischemia-Reperfusion Injury via
      Notch1/Hes1-Mediated Activation of Pten/Akt Signaling.
AB  - Diabetes exacerbates oxidative/nitrative stress during myocardial ischemia
      reperfusion (MI/R) injury. Recent studies highlighted the cardioprotective
      actions of polydatin. However, its effect on diabetic MI/R injury and the
      underlying mechanisms remain unknown. This work was undertaken to evaluate the
      effect of polydatin on diabetic MI/R injury with a focus on Notch1/Hes1 signaling
      and myocardial oxidative/nitrative stress. Streptozotocin- (STZ-) induced
      diabetic rats were administered with polydatin (20 mg/kg/d) in the absence or
      presence of DAPT (a gamma-secretase inhibitor) or LY294002 (a PI3K/Akt inhibitor)
      and then subjected to MI/R injury. Polydatin administration preserved cardiac
      function and reduced myocardial infarct size. Moreover, polydatin ameliorated
      myocardial oxidative/nitrative stress damage as evidenced by decreased myocardial
      superoxide generation, malondialdehyde, gp91 phox expression, iNOS expression, NO
      metabolite level, and nitrotyrosine content and increased eNOS phosphorylation.
      However, these effects were blocked by DAPT administration. DAPT also inhibited
      the stimulatory effect of polydatin on the Notch1/Hes1-Pten/Akt signaling pathway
      in a diabetic myocardium. Additionally, LY294002 not only abolished polydatin's
      antiapoptotic effect but also reversed its inhibitory effect on myocardial
      oxidative/nitrative stress. Polydatin effectively reduced MI/R injury and
      improved left ventricular functional recovery under diabetic condition by
      ameliorating oxidative/nitrative stress damage. Importantly, Notch1/Hes1-mediated
      activation of Pten/Akt signaling played a crucial role in this process.

PMID- 29636839
TI  - Equisetum arvense L. Extract Induces Antibacterial Activity and Modulates
      Oxidative Stress, Inflammation, and Apoptosis in Endothelial Vascular Cells
      Exposed to Hyperosmotic Stress.
AB  - Background: The antimicrobial activity of the Equisetum arvense L. extract and
      the mechanisms involved in the in vitro effects on endothelial vascular cells
      exposed to hyperosmotic stress were evaluated. Methods: Antimicrobial activity
      was evaluated by disk diffusion method and minimum inhibitory concentration (MIC)
      determination, and oxidative stress, inflammation, and apoptosis, in pretreatment
      with Equisetum arvense L., caffeic acid, and cathechin, were quantified. Results:
      The results have shown that Equisetum arvense L. exhibited antibacterial effects
      only on pathogenic gram-positive cocci. The modulatory activity of Equisetum
      arvense L. on endothelial cells exposed to hypertonic medium was different and
      depended on the concentration used. Low concentrations of tested compounds
      exerted antioxidant effect and diminished the activity of caspase-8 and also
      increased IkappaB expression while in high doses, Equisetum arvense L. was
      prooxidant, induced apoptosis, and decreased IL-6 secretion. Conclusions: These
      experimental findings suggest that Equisetum arvense L. has antibacterial effects
      on gram-positive cocci and, administered in low dose, may be a new therapeutic
      approach for diseases associated with hypertonic conditions or oxidative stress
      and apoptosis.

PMID- 29636836
TI  - Insights on Localized and Systemic Delivery of Redox-Based Therapeutics.
AB  - Reactive oxygen and nitrogen species are indispensable in cellular physiology and
      signaling. Overproduction of these reactive species or failure to maintain their
      levels within the physiological range results in cellular redox dysfunction,
      often termed cellular oxidative stress. Redox dysfunction in turn is at the
      molecular basis of disease etiology and progression. Accordingly, antioxidant
      intervention to restore redox homeostasis has been pursued as a therapeutic
      strategy for cardiovascular disease, cancer, and neurodegenerative disorders
      among many others. Despite preliminary success in cellular and animal models,
      redox-based interventions have virtually been ineffective in clinical trials. We
      propose the fundamental reason for their failure is a flawed delivery approach.
      Namely, systemic delivery for a geographically local disease limits the
      effectiveness of the antioxidant. We take a critical look at the literature and
      evaluate successful and unsuccessful approaches to translation of redox
      intervention to the clinical arena, including dose, patient selection, and
      delivery approach. We argue that when interpreting a failed antioxidant-based
      clinical trial, it is crucial to take into account these variables and
      importantly, whether the drug had an effect on the redox status. Finally, we
      propose that local and targeted delivery hold promise to translate redox-based
      therapies from the bench to the bedside.

PMID- 29636840
TI  - Yeast Cells Exposed to Exogenous Palmitoleic Acid Either Adapt to Stress and
      Survive or Commit to Regulated Liponecrosis and Die.
AB  - A disturbed homeostasis of cellular lipids and the resulting lipotoxicity are
      considered to be key contributors to many human pathologies, including obesity,
      metabolic syndrome, type 2 diabetes, cardiovascular diseases, and cancer. The
      yeast Saccharomyces cerevisiae has been successfully used for uncovering
      molecular mechanisms through which impaired lipid metabolism causes lipotoxicity
      and elicits different forms of regulated cell death. Here, we discuss mechanisms
      of the "liponecrotic" mode of regulated cell death in S. cerevisiae. This mode of
      regulated cell death can be initiated in response to a brief treatment of yeast
      with exogenous palmitoleic acid. Such treatment prompts the incorporation of
      exogenously added palmitoleic acid into phospholipids and neutral lipids. This
      orchestrates a global remodeling of lipid metabolism and transfer in the
      endoplasmic reticulum, mitochondria, lipid droplets, and the plasma membrane.
      Certain features of such remodeling play essential roles either in committing
      yeast to liponecrosis or in executing this mode of regulated cell death. We also
      outline four processes through which yeast cells actively resist liponecrosis by
      adapting to the cellular stress imposed by palmitoleic acid and maintaining
      viability. These prosurvival cellular processes are confined in the endoplasmic
      reticulum, lipid droplets, peroxisomes, autophagosomes, vacuoles, and the
      cytosol.

PMID- 29636842
TI  - A Novel Mechanism of Mesenchymal Stromal Cell-Mediated Protection against Sepsis:
      Restricting Inflammasome Activation in Macrophages by Increasing Mitophagy and
      Decreasing Mitochondrial ROS.
AB  - Sepsis, a systemic inflammatory response to infection, is the leading cause of
      death in the intensive care unit (ICU). Previous studies indicated that
      mesenchymal stromal cells (MSCs) might have therapeutic potential against sepsis.
      The current study was designed to investigate the effects of MSCs on sepsis and
      the underlying mechanisms focusing on inflammasome activation in macrophages. The
      results demonstrated that the bone marrow-derived mesenchymal stem cells (BMSCs)
      significantly increased the survival rate and organ function in cecal ligation
      and puncture (CLP) mice compared with the control-grouped mice. BMSCs
      significantly restricted NLRP3 inflammasome activation, suppressed the generation
      of mitochondrial ROS, and decreased caspase-1 and IL-1beta activation when
      cocultured with bone marrow-derived macrophages (BMDMs), the effects of which
      could be abolished by Mito-TEMPO. Furthermore, the expression levels of caspase
      1, IL-1beta, and IL-18 in BMDMs were elevated after treatment with mitophagy
      inhibitor 3-MA. Thus, BMSCs exert beneficial effects on inhibiting NLRP3
      inflammasome activation in macrophages primarily via both enhancing mitophagy and
      decreasing mitochondrial ROS. These findings suggest that restricting
      inflammasome activation in macrophages by increasing mitophagy and decreasing
      mitochondrial ROS might be a crucial mechanism for MSCs to combat sepsis.

PMID- 29636843
TI  - Oxidative Stress-Mediated Overexpression of Uracil DNA Glycosylase in Leishmania
      donovani Confers Tolerance against Antileishmanial Drugs.
AB  - Leishmania donovani is an intracellular protozoan parasite that causes endemic
      tropical disease visceral leishmaniasis (VL). Present drugs used against this
      fatal disease are facing resistance and toxicity issues. Survival of leishmania
      inside the host cells depends on the parasite's capacity to cope up with highly
      oxidative environment. Base excision repair (BER) pathway in L. donovani remains
      unexplored. We studied uracil DNA glycosylase (UNG), the key enzyme involved in
      BER pathway, and found that the glycosylase activity of recombinant LdUNG
      (Leishmania donovani UNG) expressed in E. coli is in sync with the activity of
      the parasite lysate under different reaction conditions. Overexpression of UNG in
      the parasite enhances its tolerance towards various agents which produce reactive
      oxygen species (ROS) and shows a higher infectivity in macrophages. Surprisingly,
      exposure of parasite to amphotericin B and sodium antimony gluconate upregulates
      the expression of UNG. Further, we found that the drug resistant parasites
      isolated from VL patients show higher expression of UNG. Mechanisms of action of
      some currently used drugs include accumulation of ROS. Our findings strongly
      suggest that targeting LdUNG would be an attractive therapeutic strategy as well
      as potential measure to tackle the problem of drug resistance in the treatment of
      leishmaniasis.

PMID- 29636844
TI  - Role of miR-200c in Myogenic Differentiation Impairment via p66Shc: Implication
      in Skeletal Muscle Regeneration of Dystrophic mdx Mice.
AB  - Duchenne muscular dystrophy (DMD) is a genetic disease associated with mutations
      of Dystrophin gene that regulate myofiber integrity and muscle degeneration,
      characterized by oxidative stress increase. We previously published that reactive
      oxygen species (ROS) induce miR-200c that is responsible for apoptosis and
      senescence. Moreover, we demonstrated that miR-200c increases ROS production and
      phosphorylates p66Shc in Ser-36. p66Shc plays an important role in muscle
      differentiation; we previously showed that p66Shc-/- muscle satellite cells
      display lower oxidative stress levels and higher proliferation rate and
      differentiated faster than wild-type (wt) cells. Moreover, myogenic conversion,
      induced by MyoD overexpression, is more efficient in p66Shc-/- fibroblasts
      compared to wt cells. Herein, we report that miR-200c overexpression in cultured
      myoblasts impairs skeletal muscle differentiation. Further, its overexpression in
      differentiated myotubes decreases differentiation indexes. Moreover, anti-miR
      200c treatment ameliorates myogenic differentiation. In keeping, we found that
      miR-200c and p66Shc Ser-36 phosphorylation increase in mdx muscles. In
      conclusion, miR-200c inhibits muscle differentiation, whereas its inhibition
      ameliorates differentiation and its expression levels are increased in mdx mice
      and in differentiated human myoblasts of DMD. Therefore, miR-200c might be
      responsible for muscle wasting and myotube loss, most probably via a p66Shc
      dependent mechanism in a pathological disease such as DMD.

PMID- 29636845
TI  - Rutin Isolated from Chrozophora tinctoria Enhances Bone Cell Proliferation and
      Ossification Markers.
AB  - Osteoporosis is a chronic disease in which the skeleton loses a weighty
      proportion of its mineralized mass and mechanical pliability. Currently available
      antiosteoporotic agents suffer adverse effects that include elevated risk of
      thrombosis and cancer. Phytochemicals may constitute a safer and effective
      option. In the current work, six flavonoids were obtained from Chrozophora
      tinctoria and identified as amentoflavone (1), apigenin-7-O-beta-d
      glucopyranoside (2), apigenin-7-O-6''-E-p-coumaroyl-beta-d-glucopyranoside (3),
      acacetin-7-O-beta-d-[alpha-l-rhamnosyl(1->6)]3''-E-p-coumaroyl glucopyranoside
      (4), apigenin-7-O-(6''-Z-p-coumaroyl)-beta-d-glucopyranoside (5), and rutin (6).
      An extensive review of the literature as well as NMR and mass spectral techniques
      was employed in order to elucidate the compound structures. Proliferation was
      enhanced in MCF7, MG-63, and SAOS-2 cells after exposure to subcytotoxic levels
      of the tested flavonoids. Rutin was chosen for subsequent studies in SAOS-2
      cells. Rutin was not found to cause any alteration in the index of proliferation
      of these cells, when examining the cell cycle distribution by DNA flowcytometric
      analysis. Rutin was, however, found to increase osteocyte and osteoblast-related
      gene expression and lower the expression of RUNX suppressor and osteoclast genes.
      When examining the influence of rutin on vitamin D levels and the activity of
      alkaline phosphatase enzyme, it was found to enhance both, while decreasing acid
      phosphatase which is a marker of osteoporosis. Thus, rutin enhances proliferation
      and ossification markers in bone cells.

PMID- 29636846
TI  - Long-Lived Termite Queens Exhibit High Cu/Zn-Superoxide Dismutase Activity.
AB  - In most organisms, superoxide dismutases (SODs) are among the most effective
      antioxidant enzymes that regulate the reactive oxygen species (ROS) generated by
      oxidative energy metabolism. ROS are considered main proximate causes of aging.
      However, it remains unclear if SOD activities are associated with organismal
      longevity. The queens of eusocial insects, such as termites, ants, and honeybees,
      exhibit extraordinary longevity in comparison with the nonreproductive castes,
      such as workers. Therefore, the queens are promising candidates to study the
      underlying mechanisms of aging. Here, we found that queens have higher Cu/Zn-SOD
      activity than nonreproductive individuals of the termite Reticulitermes speratus.
      We identified three Cu/Zn-SOD sequences and one Mn-SOD sequence by RNA sequencing
      in R. speratus. Although the queens showed higher Cu/Zn-SOD activity than the
      nonreproductive individuals, there were no differences in their expression levels
      of the Cu/Zn-SOD genes RsSOD1 and RsSOD3A. Copper (Cu2+ and Cu+) is an essential
      cofactor for Cu/Zn-SOD enzyme activity, and the queens had higher concentrations
      of copper than the workers. These results suggest that the high Cu/Zn-SOD
      activity of termite queens is related to their high levels of the cofactor rather
      than gene expression. This study highlights that Cu/Zn-SOD activity contributes
      to extraordinary longevity in termites.

PMID- 29636841
TI  - Regulation of Tumor Progression by Programmed Necrosis.
AB  - Rapidly growing malignant tumors frequently encounter hypoxia and nutrient (e.g.,
      glucose) deprivation, which occurs because of insufficient blood supply. This
      results in necrotic cell death in the core region of solid tumors. Necrotic cells
      release their cellular cytoplasmic contents into the extracellular space, such as
      high mobility group box 1 (HMGB1), which is a nonhistone nuclear protein, but
      acts as a proinflammatory and tumor-promoting cytokine when released by necrotic
      cells. These released molecules recruit immune and inflammatory cells, which
      exert tumor-promoting activity by inducing angiogenesis, proliferation, and
      invasion. Development of a necrotic core in cancer patients is also associated
      with poor prognosis. Conventionally, necrosis has been thought of as an
      unregulated process, unlike programmed cell death processes like apoptosis and
      autophagy. Recently, necrosis has been recognized as a programmed cell death,
      encompassing processes such as oncosis, necroptosis, and others. Metabolic stress
      induced necrosis and its regulatory mechanisms have been poorly investigated
      until recently. Snail and Dlx-2, EMT-inducing transcription factors, are
      responsible for metabolic stress-induced necrosis in tumors. Snail and Dlx-2
      contribute to tumor progression by promoting necrosis and inducing EMT and
      oncogenic metabolism. Oncogenic metabolism has been shown to play a role(s) in
      initiating necrosis. Here, we discuss the molecular mechanisms underlying
      metabolic stress-induced programmed necrosis that promote tumor progression and
      aggressiveness.

PMID- 29636847
TI  - Cyclodextrin Enhances Corneal Tolerability and Reduces Ocular Toxicity Caused by
      Diclofenac.
AB  - With advances in refractive surgery and demand for cataract removal and lens
      replacement, the ocular use of nonsteroidal anti-inflammatory drugs (NSAIDs) has
      increased. One of the most commonly used NSAIDs is diclofenac (Diclo). In this
      study, cyclodextrins (CDs), alpha-, beta-, gamma-, and HP-beta-CDs, were
      investigated with in vitro irritation and in vivo ulceration models in rabbits to
      reduce Diclo toxicity. Diclo-, alpha-, beta-, gamma-, and HP-beta-CD inclusion
      complexes were prepared and characterized and Diclo-CD complexes were evaluated
      for corneal permeation, red blood cell (RBCs) haemolysis, corneal
      opacity/permeability, and toxicity. Guest- (Diclo-) host (CD) solid inclusion
      complexes were formed only with beta-, gamma-, and HP-beta-CDs. Amphipathic
      properties for Diclo were recorded and this surfactant-like functionality might
      contribute to the unwanted effects of Diclo on the surface of the eye. Contact
      angle and spreading coefficients were used to assess Diclo-CDs in solution.
      Reduction of ocular toxicity 3-fold to16-fold and comparable corneal permeability
      to free Diclo were recorded only with Diclo-gamma-CD and Diclo-HP-beta-CD
      complexes. These two complexes showed faster healing rates without scar formation
      compared with exposure to the Diclo solution and to untreated groups. This study
      also highlighted that Diclo-gamma-CD and Diclo-HP-beta-CD demonstrated fast
      healing without scar formation.

PMID- 29636848
TI  - Early Postweaning Treatment with Dimethyl Fumarate Prevents Prenatal
      Dexamethasone- and Postnatal High-Fat Diet-Induced Programmed Hypertension in
      Male Rat Offspring.
AB  - Prenatal dexamethasone (DEX) exposure, postnatal high-fat (HF) intake, and
      oxidative stress are closely related to the development of hypertension. Nuclear
      factor erythroid-derived 2-related factor 2 (Nrf2) regulates oxidative stress.
      Dimethyl fumarate (DMF) reportedly activates Nrf2 and protects against oxidative
      stress damage. We examined a 4-month-old male rat offspring from five groups (n =
      8 for each group): control, DEX (0.1 mg/kg i.p. from a gestational age of 16 to
      22 days), HF (D12331 diet from weaning to 4 months of age), and DEX + HF, DEX +
      HF + DMF (50 mg/kg/day via gastric gavage for 3 weeks after weaning). We found
      that postnatal HF intake aggravated prenatal DEX-induced hypertension in adult
      male offspring, which could be prevented by DMF treatment. The beneficial effects
      of DMF treatment include an increase in renal Nrf2 gene expression, reduction of
      oxidative stress, decrease in plasma asymmetric dimethylarginine (ADMA) and renal
      soluble epoxide hydrolase protein levels, increase in the l-arginine-to-ADMA
      ratio, and activation of genes related to nutrient sensing and autophagy (e.g.,
      Pparb, Pparg, Ppargc1a, Ulk1, and Atg5). In conclusion, better understanding of
      the impact of the Nrf2 signaling pathway in the two-hit model will aid in
      protecting children exposed to antenatal corticosteroids and a postnatal HF diet
      from programmed hypertension.

PMID- 29636849
TI  - Photobiomodulation Leads to Reduced Oxidative Stress in Rats Submitted to High
      Intensity Resistive Exercise.
AB  - The aim of this study was to determine whether oxidative stress markers are
      influenced by low-intensity laser therapy (LLLT) in rats subjected to a high
      intensity resistive exercise session (RE). Female Wistar rats divided into three
      experimental groups (Ctr: control, 4J: LLLT, and RE) and subdivided based on the
      sampling times (instantly or 24 h postexercise) underwent irradiation with LLLT
      using three-point transcutaneous method on the hind legs, which was applied to
      the gastrocnemius muscle at the distal, medial, and proximal points. Laser (4J)
      or placebo (device off) were carried out 60 sec prior to RE that consisted of
      four climbs bearing the maximum load with a 2 min time interval between each
      climb. Lipoperoxidation levels and antioxidant capacity were obtained in muscle.
      Lipoperoxidation levels were increased (4-HNE and CL markers) instantly post-RE.
      LLLT prior to RE avoided the increase of the lipid peroxidation levels. Similar
      results were also notified for oxidation protein assays. The GPx and FRAP
      activities did not reduce instantly or 24 h after RE. SOD increased 24 h after
      RE, while CAT activity did not change with RE or LLLT. In conclusion, LLLT prior
      to RE reduced the oxidative stress markers, as well as, avoided reduction, and
      still increased the antioxidant capacity.

PMID- 29636851
TI  - Effect of N-Acetylcysteine on Antioxidant Defense, Oxidative Modification, and
      Salivary Gland Function in a Rat Model of Insulin Resistance.
AB  - Oxidative stress plays a crucial role in the salivary gland dysfunction in
      insulin resistance (IR). It is not surprising that new substances are constantly
      being sought that will protect against the harmful effects of IR in the oral
      cavity environment. The purpose of this study was to evaluate the effect of N
      acetylcysteine (NAC) on oxidative stress and secretory function of salivary
      glands in a rat model of insulin resistance. Rats were divided into 4 groups: C
      normal diet, C + NAC-normal diet + NAC, HFD-high-fat diet, and HFD + NAC. We have
      demonstrated that NAC elevated enzymatic (superoxide dismutase, catalase, and
      peroxidase) and nonenzymatic antioxidants (reduced glutathione (GSH) and total
      antioxidant capacity (TAS)) in the parotid glands of HFD + NAC rats, while in the
      submandibular glands increased only GSH and TAS levels. NAC protects against
      oxidative damage only in the parotid glands and increased stimulated salivary
      secretion; however, it does not increase the protein secretion in the both
      salivary glands. Summarizing, NAC supplementation prevents the decrease of
      stimulated saliva secretion, seen in the HFD rats affected. NAC improves the
      antioxidative capacity of the both glands and protects against oxidative damage
      to the parotid glands of IR rats.

PMID- 29636852
TI  - Role of Exercise-Induced Cardiac Remodeling in Ovariectomized Female Rats.
AB  - Myocardial extracellular matrix (ECM) is essential for proper cardiac function
      and structural integrity; thus, the disruption of ECM homeostasis is associated
      with several pathological processes. Female Wistar rats underwent surgical
      ovariectomy (OVX) or sham operation (SO) and were then divided into eight
      subgroups based on the type of diet (standard chow or high-triglyceride diet/HT)
      and exercise (with or without running). After 12 weeks, cardiac MMP-2 activity,
      tissue inhibitor of metalloproteinase-2, content of collagen type I, the level of
      nitrotyrosine (3-NT) and glutathione (GSH), and the ratio of infarct size were
      determined. Our results show that OVX and HT diet caused an excessive
      accumulation of collagen; however, this increase was not observed in the trained
      animals. Twelve weeks of exercise promoted elevation in the levels of 3-NT and
      GSH and similarly an increase in MMP-2 activity of both SO and OVX animals. The
      high infarct-size ratio caused by OVX and HT diet was mitigated by physical
      exercise. Our findings demonstrate that ovarian estrogen loss and HT diet caused
      collagen accumulation and increased ratio of the infarct size. However, exercise
      induced cardiac remodeling serves as a compensatory mechanism by enhancing MMP-2
      activity and reducing fibrosis, thus minimizing the ischemia/reperfusion injury.

PMID- 29636853
TI  - Hydrogen Sulfide Attenuates LPS-Induced Acute Kidney Injury by Inhibiting
      Inflammation and Oxidative Stress.
AB  - In order to investigate the protective mechanism of hydrogen sulfide (H2S) in
      sepsis-associated acute kidney injury (SA-AKI), ten AKI patients and ten healthy
      controls were enrolled. In AKI patients, levels of creatinine (Cre), urea
      nitrogen (BUN), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL
      1beta), and myeloperoxidase (MPO) activity as well as concentrations of
      malondialdehyde (MDA) and hydrogen peroxide (H2O2) were significantly increased
      compared with those of controls. However, plasma level of H2S decreased and was
      linearly correlated with levels of Cre and BUN. After that, an AKI mouse model by
      intraperitoneal lipopolysaccharide (LPS) injection was constructed for in vivo
      study. In AKI mice, H2S levels decreased with the decline of 3-MST activity and
      expression; similar changes were observed in other indicators mentioned above.
      However, the protein expressions of TLR4, NLRP3, and caspase-1 in mice kidney
      tissues were significantly increased 6 h after LPS injection. NaHS could improve
      renal function and kidney histopathological changes, attenuate LPS-induced
      inflammation and oxidative stress, and inhibit expressions of TLR4, NLRP3, and
      caspase-1. Our study demonstrated that endogenous H2S is involved in the
      pathogenesis of SA-AKI, and exogenous H2S exerts protective effects against LPS
      induced AKI by inhibiting inflammation and oxidative stress via the TLR4/NLRP3
      signaling pathway.

PMID- 29636854
TI  - Epigallocatechin-3-Gallate (EGCG) Promotes Autophagy-Dependent Survival via
      Influencing the Balance of mTOR-AMPK Pathways upon Endoplasmic Reticulum Stress.
AB  - The maintenance of cellular homeostasis is largely dependent on the ability of
      cells to give an adequate response to various internal and external stimuli. We
      have recently proposed that the life-and-death decision in endoplasmic reticulum
      (ER) stress response is defined by a crosstalk between autophagy, apoptosis, and
      mTOR-AMPK pathways, where the transient switch from autophagy-dependent survival
      to apoptotic cell death is controlled by GADD34. The aim of the present study was
      to investigate the role of epigallocatechin-3-gallate (EGCG), the major
      polyphenol of green tea, in promoting autophagy-dependent survival and to verify
      the key role in connecting GADD34 with mTOR-AMPK pathways upon prolonged ER
      stress. Our findings, obtained by using HEK293T cells, revealed that EGCG
      treatment is able to extend cell viability by inducing autophagy. We confirmed
      that EGCG-induced autophagy is mTOR-dependent and PKA-independent; furthermore,
      it also required ULK1. We show that pretreatment of cells with EGCG diminishes
      the negative effect of GADD34 inhibition (by guanabenz or siGADD34 treatment) on
      autophagy. EGCG was able to delay apoptotic cell death by upregulating autophagy
      dependent survival even in the absence of GADD34. Our data suggest a novel role
      for EGCG in promoting cell survival via shifting the balance of mTOR-AMPK
      pathways in ER stress.

PMID- 29636850
TI  - Oxidant/Antioxidant Imbalance in Alzheimer's Disease: Therapeutic and Diagnostic
      Prospects.
AB  - Alzheimer's disease (AD) is the most common cause of dementia and a great
      socioeconomic burden in the aging society. Compelling evidence demonstrates that
      molecular change characteristics for AD, such as oxidative stress and amyloid
      beta (Abeta) oligomerization, precede by decades the onset of clinical dementia
      and that the disease represents a biological and clinical continuum of stages,
      from asymptomatic to severely impaired. Nevertheless, the sequence of the early
      molecular alterations and the interplay between them are incompletely understood.
      This review presents current knowledge about the oxidative stress-induced
      impairments and compromised oxidative stress defense mechanisms in AD brain and
      the cross-talk between various pathophysiological insults, with the focus on
      excessive reactive oxygen species (ROS) generation and Abeta overproduction at
      the early stages of the disease. Prospects for AD therapies targeting
      oxidant/antioxidant imbalance are being discussed, as well as for the development
      of novel oxidative stress-related, blood-based biomarkers for early, noninvasive
      AD diagnostics.

PMID- 29636855
TI  - Fisetin Confers Cardioprotection against Myocardial Ischemia Reperfusion Injury
      by Suppressing Mitochondrial Oxidative Stress and Mitochondrial Dysfunction and
      Inhibiting Glycogen Synthase Kinase 3beta Activity.
AB  - Acute myocardial infarction (AMI) is the leading cause of morbidity and mortality
      worldwide. Timely reperfusion is considered an optimal treatment for AMI.
      Paradoxically, the procedure of reperfusion can itself cause myocardial tissue
      injury. Therefore, a strategy to minimize the reperfusion-induced myocardial
      tissue injury is vital for salvaging the healthy myocardium. Herein, we
      investigated the cardioprotective effects of fisetin, a natural flavonoid,
      against ischemia/reperfusion (I/R) injury (IRI) using a Langendorff isolated
      heart perfusion system. I/R produced significant myocardial tissue injury, which
      was characterized by elevated levels of lactate dehydrogenase and creatine kinase
      in the perfusate and decreased indices of hemodynamic parameters. Furthermore,
      I/R resulted in elevated oxidative stress, uncoupling of the mitochondrial
      electron transport chain, increased mitochondrial swelling, a decrease of the
      mitochondrial membrane potential, and induction of apoptosis. Moreover, IRI was
      associated with a loss of the mitochondrial structure and decreased mitochondrial
      biogenesis. However, when the animals were pretreated with fisetin, it
      significantly attenuated the I/R-induced myocardial tissue injury, blunted the
      oxidative stress, and restored the structure and function of mitochondria.
      Mechanistically, the fisetin effects were found to be mediated via inhibition of
      glycogen synthase kinase 3beta (GSK3beta), which was confirmed by a biochemical
      assay and molecular docking studies.

PMID- 29636857
TI  - MiR-22 down-regulates the proto-oncogene ATP citrate lyase to inhibit the growth
      and metastasis of breast cancer.
AB  - Breast cancer, the most common malignancy in women worldwide, places a heavy
      economic burden and mental stress on families and society. Previous research
      showed that abnormal expression of miRNAs was closely related to the occurrence,
      metastasis, and angiogenesis of breast cancer. And in this study, the abnormal
      expression of miR-22 was detected by RT-PCR in the paired breast cancer tissues
      and adjacent non-tumor tissues. CCK-8 and wound healing assays were performed to
      evaluate the effects of the proto-oncogene ATP citrate lyase (ACLY) on the growth
      and metastasis of breast cancer MCF-7 cells. The results showed that miR-22
      inhibited the growth and metastasis of MCF-7 cells by down-regulating the
      expression of ACLY. In conclusion, this study elucidated the roles of miR-22 in
      regulation of breast cancer differentiation and migration, which provides a
      target for early diagnose and therapy of breast cancer.

PMID- 29636856
TI  - 15d-PGJ2 is a new hope for controlling tumor growth.
AB  - 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2), a natural PPARgamma agonist, has
      been investigated for over a decade. Studies have revealed that it has
      proapoptotic, anti-inflammatory, antiangiogenic, and anti-metastatic abilities,
      as well as a significant anticancer effect. However, the mechanisms underlying
      the actions of 15d-PGJ2 on various tumors are only partially known. In this
      review, we discuss the recent progress in elucidating these mechanisms.
      Understanding the various functions and mechanisms of 15d-PGJ2 are crucial for
      the development of new therapies for controlling tumor growth and providing the
      basis for further research.

PMID- 29636859
TI  - Overexpression of long non-coding RNA RP11-396F22.1 correlates poor prognosis of
      patients with early-stage cervical cancer.
AB  - OBJECTIVE: The expression level and clinical significances of long non-coding
      RNAs (LncRNAs) are presently unknown in the early-stage cervical cancer (CC).
      This study was aimed to explore the expression signatures of lncRNAs between
      normal and cervix carcinoma tissues and the prognostic value of LncRNAs in early
      stage CC patients. MATERIALS AND METHODS: The patients diagnosed with FIGO stage
      I-IIb CC of the First Affiliated Hospital of Sun Yat-sen University between
      January 1st 2006 and December 31st 2009 were retrospectively reviewed. Molecular
      microarray was conducted to identify differentially expression profiles of
      LncRNAs. In situ hybridization was applied for detection of candidate lncRNAs in
      cervical tissues. RESULTS: A total of 2574 upregulated lncRNAs and 3270
      downregulated lncRNAs with significantly differential expression (>=2.0-fold)
      were identified. Among the differentially expressed lncRNAs, RP11-396F22.1
      expression was one of the most significantly overexpressed in the CC tissues
      compared to nomal cervical tissues (P<0.001). In situ hybridization confirmed
      RP11-396F22.1 expression was highly expressed in cancerous tissues. The results
      of Scratch and Transwell test showed that the migration ability decreased
      remarkably in transfected group (P<0.001). Moreover, the coding gene cpne8 was
      significantly upregulated by RP11-396F22.1 knockdown (P=0.035). CONCLUSIONS:
      These findings demonstrate that LncRNA RP11-396F22.1 might be a potent biomarker
      for CC progression.

PMID- 29636858
TI  - Ephedrine hydrochloride protects mice from staphylococcus aureus-induced
      peritonitis.
AB  - Staphylococcus aureus is a Gram-positive (G+) bacterium that causes a wide range
      of diseases in humans and livestock. Therefore, the development of innovative and
      effective therapies is essential for the treatment of S. aureus-induced severe
      infections. Ephedrine hydrochloride (EH) is a compound derived from ephedrine and
      is widely used for the management of cardiovascular diseases and hypotension. The
      results of our previous studies demonstrated that EH has anti-inflammatory
      activity in macrophages and protects against endotoxic shock. However, whether EH
      regulates the function of dendritic cells (DCs) and the immune response in S.
      aureus-induced infection is unknown. In this study, the anti-inflammatory and
      regulatory activity of EH on DCs was evaluated. EH increased the production of
      anti-inflammatory cytokine IL-10 and decreased the production of proinflammatory
      cytokines TNF-alpha and IL-12 in DCs stimulated with peptidoglycan (PGN), the
      main cell wall component in G+ bacteria. The PI3K/Akt and p38 MAPK signaling
      pathways controlled EH-induced IL-10 expression and EH-inhibited TNF-alpha
      expression, respectively. The PGN-induced expression of co-stimulatory molecules
      CD40, CD80, CD86, and MHC class II molecule Iab was down-regulated in DCs by EH.
      Furthermore, EH protected the liver and kidney and increased the survival rate of
      mice with S. aureus-induced peritonitis. In conclusion, EH helps to keep immune
      homeostasis and alleviate organ damage during S. aureus-induced peritonitis.
      Therefore, EH may be a promising drug candidate in the treatment of S. aureus
      induced severe infections and other invasive G+ bacterial infections.

PMID- 29636860
TI  - YM155 enhances docetaxel efficacy in ovarian cancer.
AB  - YM155 (Sepantronium bromide) is a potent small molecule inhibitor of survivin by
      suppression of survivin expression and shows the promising anticancer activity in
      many types of cancers. Docetaxel (Taxotere(r)) is a member of the taxane drugs
      used in the treatment of a number of cancers in clinic. Despite the therapeutic
      efficacy of docetaxel is encouraging, the emergent resistance is an urgent issue.
      In this study, we investigate the effect of YM155 on docetaxel efficacy in
      ovarian cancer cells. Our data showed that YM155 actively induced cell growth
      inhibition, cell cycle arrest and apoptosis with downregualtion of survivin in
      ovarian cancer cells. Moreover, YM155 increased the intracellular ROS levels, and
      pretreatment with either NAC or GSH partially reversed the YM155-induced ROS
      accumulation and apoptosis only in the parental A2780 cells, but not in the
      resistant A2780/Taxol cells. Furthermore, YM155 enhanced docetaxel efficacy to
      inhibit the growth and induce apoptosis in ovarian cancer cells. Take together,
      our results suggested that combination of YM155 and docetaxel may be a feasible
      strategy for the treatment of ovarian cancer.

PMID- 29636861
TI  - Inner ear structure of miniature pigs measured by multi-planar reconstruction
      techniques.
AB  - To study the structures of the scala vestibuli and tympani of miniature pigs in
      order to evaluate the feasibility of using miniature pigs as the animal model for
      cochlear implant. The temporal bones of three miniature pigs with normal hearing
      were scanned by micro-CT. With the aid of the Mimics software, we reconstructed
      the 3D structure of inner ear basing on the serial images of the miniature pig,
      and obtained dimensions of the scala vestibuli and tympani with multi-planar
      reconstruction (MPR) technique. The constructed slicing images displayed the fine
      structures of the cochlea. The results of our study showed that the cross
      sectional areas of the scala tympani were greatest at 2.67 +/- 0.90 mm2 when the
      circumferential length from the starting point of basal turn of the cochlea
      reached to 1.16 mm. The scala vestibuli has a largest width and height at the
      starting point of basal turn. The width and the height were 2.65 +/- 0.45 mm and
      2.43 +/- 0.2 mm respectively. The largest width and height of the scala tympani
      were 2.17 +/- 0.30 mm and 1.83 +/- 0.42 mm. The result of our study suggests that
      the cochlea of miniature pigs is highly consistent with human's. Miniature pigs
      may be used as a new model for cochlear implant. MPR technique may be used as a
      new approach to obtain further information of patient's cochlea in surgeons which
      is helpful to select suitable cochlear implant devices and surgery approach.

PMID- 29636862
TI  - Cyclooxygenase-2 deficiency causes delayed ossification of lumbar vertebral
      endplates.
AB  - Based on previous findings that cyclooxygenase-2 (COX-2) is a critical molecule
      in chondrocyte differentiation and skeletal repair, we hypothesized that COX-2
      deficiency or inhibition affects the ossification of vertebral endplates (VEP)
      and degeneration of intervertebral discs (IVD) and thus is involved in the
      pathogenesis of low back pain (LBP). We aimed to delineate the COX-2 working
      mechanism and its interacting molecules, and to explore the effect of NSAIDs and
      selective COX-2 inhibitor on degenerative spinal diseases. Here, lumbar spinal
      samples harvested from Cox-2 mutant (Cox-2-/-) and wild type (WT) mice were used
      for histological examinations. Nucleus pulposus (NP) cells isolated from rat were
      treated with PGE-2. Mouse endplate chondrocytes (mEC) isolated from mice were
      treated with a recombinant sonic hedgehog (Shh) protein. A mouse IVD organ
      culture system was established and treated COX-2 inhibitor Celecoxib. Human
      lumbar endplate chondrocytes were cultured and treated with Celecoxib.
      Immunohistochemical (IHC) studies were done in the human and mouse VEP samples.
      Radiographic and histological examinations revealed delayed VEP ossification in
      Cox-2-/- mice compared to WT ones. Decreased PGE-2 expression was found to
      promote Shh expression in rat NP cells, while Shh increased noggin expression in
      mEC. IHC showed that noggin expression was increased while pSmad1 expression
      decreased in the VEP of Cox-2-/- mice. Human VEP samples from patients with
      severe IVD degeneration showed decreased expression of Shh and noggin and
      increased expression of COX-2 and pSmad1 compared with milder cases. In cultured
      mouse IVDs and human endplate chondrocytes, Celecoxib enhanced expression of Shh
      and noggin and decreased Smad1 phosphorylation. In conclusion, COX-2/PGE-2 axis
      plays an important role in VEP ossification and IVD degeneration through
      crosstalk with Shh and BMP signaling pathways. These findings may facilitate
      clinical use of COX-2 inhibitor to prevent LBP progression.

PMID- 29636863
TI  - S-phase kinase-associated protein 2 impairs the inhibitory effects of miR-1236-3p
      on bladder tumors.
AB  - We have previously demonstrated that miR-1236-3p has the robust ability to up
      regulate p21 expression by targeting the p21 promoter, thus inhibiting bladder
      cancer progression. Microarray experiments displayed that miR-1236-3p
      significantly increased the expression of the oncogenic F-box protein S-phase
      kinase-associate protein 2 (Skp2) while activating p21 expression in bladder
      cancer cells. Here, we confirmed that Skp2 was over-expressed following
      transfection with miR-1236-3p. Further, we demonstrated that miR-1236-3p and its
      sequence homology dsRNA, dsRNA-245 (which is completely complementary to the p21
      promoter), both are able to potently induce p21 expression. We found that dsRNA
      245 did not induce changes in Skp2 expression, while miR-1236-3p could increase
      Skp2 expression; this influence was independent of p21 activation. Moreover,
      transfection of miR-1236-3p or dsRNA-245 into bladder cancer cells significantly
      inhibited cell proliferation and clonegenesis and induced cell cycle arrest
      mainly by regulating p21 expression. However, the growth inhibition caused by
      dsRNA-245 was more effective than that caused by miR-1236-3p. This difference in
      effect size is mainly related to the miR-1236-3p-induced expression of Skp2. In
      summary, our results provided evidence that both endogenous and exogenous small
      RNAs might function to induce p21 expression by interacting with the same
      promoter region, therefore impeding bladder cancer cell growth. Additionally, our
      results indicated that microRNA activation can activate the expression of some
      tumor suppressor genes as well as some oncogenes. This indicated the need for the
      further study of clinical applications of RNA activation.

PMID- 29636864
TI  - MicroRNA-223 inhibits deposition of the extracellular matrix by airway smooth
      muscle cells through targeting IGF-1R in the PI3K/Akt pathway.
AB  - Asthma is a wide-spread disease that significantly impacts health throughout the
      world. A key aspect of the pathology of the disease is the remodeling of the
      airways by airway smooth muscle cells (ASMCs). MicroRNAs play an important role
      in post-transcriptional gene regulation and are involved in numerous biological
      functions, including those linked to asthma. A large number of microRNAs have
      been identified and investigated in various cell types to assess their function.
      In the present study, the role and potential mechanisms of miR-223 in ASMCs were
      investigated. Overexpression of miR-223 was found to induce a phenotypic switch
      in ASMCs that led to decreased expression of proteins involved in the
      extracellular matrix, such as alpha-SMA (ACTA2), and type I and III collagens.
      Inhibition of miR-223 caused the opposite result. However, unlike mast cells,
      neither overexpression nor inhibition of miR-223 affected cell viability or
      apoptosis in ASMCs. To further understand the effects of miR-223 on ASMCs, we
      applied bioinformatics analysis using predictive software, in combination with
      western blotting, to reveal that insulin-like growth factor-1 receptor (IGF-1R)
      was the functional target of miR-223 that leads to the phenotypic switch of
      ASMCs. Suppression of luciferase activity in a reporter containing the 3'
      untranslated region (3'-UTR) of IGF-1R confirmed that this region is the target
      for the miRNA. Finally, we showed that miR-223 suppressed IGF-1R expression and
      decreased downstream phosphorylation of Akt (AKT1) in ASMCs. In conclusion, our
      data demonstrate that miR-223 exerts an inhibitory effect on the fibrotic
      phenotypes of ASMCs via the PI3K/Akt signaling pathway and IGF-1R is the likely
      functional target of the microRNA.

PMID- 29636865
TI  - Aerobic exercise relieved vascular cognitive impairment via NF-kappaB/miR
      503/BDNF pathway.
AB  - OBJECTIVE: To investigate the mechanism of aerobic exercise in the relief of
      vascular cognitive impairment (VCI). MATERIALS AND METHODS: Latency of Water Maze
      test was measured at sham, 2VO, 2VO+EX groups. miR-503 and BDNF mRNA levels were
      detected by quantitative real-time PCR. Protein levels of NF-kappaB and BDNF were
      detected by Western blot. Hippocampal neuron cell apoptosis was detected by flow
      cytometry. Luciferase reporter assay was conducted to investigate the effect of
      miR-503 on BDNF. RESULTS: Latency of Water Maze test in 2VO group was longer than
      Sham group, while exercise shortened the latency. The expressions of NF-kappaB
      and miR-503 in 2VO group were higher than Sham group, while exercise
      downregulated the expressions. BDNF level in 2VO group were downregulated than
      Sham group, while exercise upregulated the levels. We also found NF-kappaB, miR
      503 levels were upregulated and BDNF level was downregulated in OGD-treated
      hippocampal neuron cells. In addition, OGD increased the expression of NF-kappaB
      and miR-503, and the expression of miR-503 was downregulated when treated with NF
      kappaB inhibitor (PDTC). Moreover, we confirmed BDNF was a direct target of miR
      503. OGD decreased the expression of BDNF, while miR-503 inhibitor reversed this
      effect. And we proved OGD induced cell apoptosis via NF-kappaB/miR-503/BDNF.
      Finally, in rats injected with miR-503 inhibitor, latency of Water Maze test was
      shortened, miR-503 expression was downregulated, and BDNF level was upregulated.
      While in rats injected with miR-503 mimic, the results were the opposite.
      CONCLUSION: Aerobic exercise relieved VCI via NF-kappaB/miR-503/BDNF pathway.

PMID- 29636866
TI  - Protective effects of PI3K/Akt signal pathway induced cell autophagy in rat knee
      joint cartilage injury.
AB  - As the major reason for limb dysfunction, osteoarthritis (OA) is closely
      correlated with the level of cellular autophagy. PI3K/Akt is a classical
      signaling pathway which regulates autophagy, but with unclear roles in OA related
      cartilage injury. Studying PI3K/Akt induced autophagy in rat knee joint cartilage
      injury and possible functional mechanism is of critical importance for clinical
      treatment. This study established a rat knee joint cartilage injury model, in
      which Akt agonist IGF-1 or autophagy inducer Rapamycin was administrated. Western
      blot was used to detect the expression level of AKT, phosphorylated AKT, Beclin-1
      and LC3-II/I. Formation of autophagosome and lysosome was assessed by
      transmission electron microscopy. HE, safranin O and toluidine blue staining was
      used to evaluate cartilage injury. TUNEL staining was performed to measure cell
      apoptosis. Real-time quantitative PCR measured the expression of cartilage injury
      indexes such as Aggrecan, Collagen II and MMP13. Compared with normal group,
      iodacetic acid treatment group showed cartilage injury, whereas AKT activation
      and autophagy induction groups had significant improvement. mRNA analysis showed
      enhanced degradation of Aggrecan and Collagen II in AKT activation and autophagy
      groups with decreased MMP13 mRNA level (P<0.05). Western blot results showed that
      after AKT activation and autophagy induction, protein levels of Beclin-1 and LC3
      II/I were remarkably elevated (P<0.05). TUNEL assay showed significant inhibition
      of cell apoptosis. In conclusion, activation of PI3K/Akt signal pathway can
      improve iodacetic acid induced rat knee joint cartilage injury through inducing
      cell autophagy.

PMID- 29636867
TI  - Microarray expression profiling and bioinformatics analysis of circular RNA
      expression in lung squamous cell carcinoma.
AB  - Circular RNAs (circRNAs) are novel noncoding RNAs with a wide range of
      physiological and pathological activities. However, the expression profile and
      roles in lung squamous cell carcinoma (LSCC) remain largely unknown. Therefore,
      we investigated the expression profile of circRNAs in three LSCC and matched
      adjacent normal tissues using microarray. Total 216 differentially expressed
      circRNAs were identified, including 135 upregulated and 81 downregulated ones in
      LSCC tissues. Bioinformatics analysis revealed that these differentially
      expressed circRNAs were potentially implicated in carcinogenesis using Gene
      ontology (GO) and KEGG pathway analyses. By constructing miRNA-circRNA
      interaction network, a total of ten key circRNAs, including 6 upregulated and 4
      downregulated circRNAs were further screened and then confirmed using qRT-PCR
      analysis in another 40 paired of LSCC tissues and adjacent normal tissues. In
      addition, Kaplan-Meier survival analysis demonstrated that the overall survival
      time of LSCC patients with high hsa_circRNA_103827 expression and low
      hsa_circRNA_000122 was significantly shorter (P<0.001). In conclusion, this study
      provides evidence that circRNAs are differentially expressed in LSCC and closely
      related to the carcinogenesis of LSCC. Among these, hsa_circRNA_103827 and
      hsa_circRNA_000122 might be served as potential prognostic biomarkers and
      therapeutic target for LSCC.

PMID- 29636868
TI  - Novasoy and genistein inhibit endometrial cancer cell proliferation through
      disruption of the AKT/mTOR and MAPK signaling pathways.
AB  - OBJECTIVES: Excess estrogen states, such as those generated by obesity, have long
      been associated with the development of type I endometrial cancers.
      Epidemiological studies have linked consumption of isoflavones with a decreased
      incidence of endometrial malignancy. Thus, our goal was to assess the effect of
      the isoflavones, novasoy and genistein, on cell proliferation, cell cycle,
      apoptosis, progesterone receptor (PR) and estrogen receptor-alpha (ERalpha)
      expression and the AKT/mTOR and MAPK pathways in endometrial cancer cells.
      METHODS: The endometrial cancer cell lines ECC-1 and RL-95-2 were used. Cell
      proliferation was assessed with MTT assay after exposure to novasoy and genistein
      at varying concentrations. Cell cycle progression was analyzed by flow cytometry.
      Apoptosis was assessed by flow cytometery for annexin V expression and ELISA for
      caspase-3 activity. Expression of ERalpha, PR and hTERT mRNA were evaluated using
      real time RT-PCR. Western immunoblotting was performed to evaluate the effects of
      novasoy and genistein on the AKT/mTOR and MAPK signaling pathways. RESULTS:
      Novasoy and genistein inhibited cell growth in a dose-dependent manner in both
      cell lines through induction of cell cycle G2 arrest and apoptosis. Treatment
      with novasoy and genistein decreased hTERT expression in a dose-dependent manner.
      Genistein decreased ERalpha mRNA expression while increasing PR expression.
      Genistein induced phosphorylation of p42/44 in a dose dependent manner in both
      cell lines but reduced phosphorylation of S6 in only the RL-95-2 cells.
      CONCLUSIONS: Novasoy and genistein inhibited cell proliferation through varying
      pathways in different cell lines but included decreased ERalpha expression and
      subsequent alteration in the expression of proteins upstream and downstream of
      the AKT/mTOR and MAPK pathways. Thus, isoflavones may be a promising therapeutic
      agent in the treatment and prevention of endometrial cancer.

PMID- 29636869
TI  - Ginsenoside Rb1 inhibit apoptosis in rat model of Alzheimer's disease induced by
      Abeta1-40.
AB  - Alzheimer's disease (AD) is the most common form of dementia and lacks disease
      altering treatments. Ginsenoside Rb1 (GsRb1), the key active compounds of
      ginsenoside found in ginseng. The present study aimed to determine whether GsRb1
      could prevent cognitive deficit and take neuroprotective effects in Abeta1-40
      induced rat model through apoptotic signaling pathway. Injection of soluble
      Abeta1-40 into the hippocampus caused impairment in learning and memory. Daily
      administration of Rb1 (12.5, 25, and 50 mg/kg, i.p.) for 14 consecutive days. All
      rats were tested for their capabilities of spatial navigation and memorization by
      Morris water maze. Apoptosis was tested using TUNEL staining in hippocampus
      neuronal cells. RT-PCR, immunohistochemical staining and western blotting were
      employed to confirm the expressions of Bcl-2, Bax and Cleaved Caspase-3. The
      results showed that Rb1 administration could prevent cognitive deficit, and
      significantly decreased the levels of Bax and Cleaved Caspase-3 meanwhile up
      regulation the level of Bcl-2 in the hippocampus. We suggest that GsRb1 may be
      effective for preventing or slowing the development of Alzheimer's disease, which
      improving cognitive and memory functions by inhibiting the levels of pro
      apoptosis mediators and improving the levels of anti-apoptosis mediators in the
      rat brain.

PMID- 29636870
TI  - Reverse mode of sodium/calcium exchanger subtype 1 contributes to detrusor
      overactivity in rats with partial bladder outflow obstruction.
AB  - To investigate whether the reverse mode of sodium/calcium exchanger subtype 1
      (NCX1) plays an important role in the excitability of detrusor cells in rats with
      partial bladder outflow obstruction (PBOO), PBOO was maintained for 6 weeks in
      forty female Wistar rats. Thirty of the animals exhibited non-voiding bladder
      contraction and comprised the DO group. An additional thirty sham-operated female
      Wistar rats were used as the control group. The expression levels of NCX1 were
      compared between the two groups by quantitative reverse transcriptase-polymerase
      chain reaction (RT-PCR), western blotting (WB), and double-label
      immunofluorescence. The contractions of detrusor strips in NCX reverse mode were
      measured in both groups using isometric tension. The role of NCX in the
      regulation of the intracellular Ca2+ concentration ([Ca2+]i) of smooth muscle
      cells was observed in reverse mode using confocal microscopy, and the current was
      evaluated in the presence of the antagonist KB-R7943 (5 MUM and 10 MUM) using the
      whole-cell patch-clamp technique. The expression of NCX1 was significantly higher
      in the DO group than in the control group, as assessed by qRT-PCR, WB analysis
      and immunofluorescence. The volume and rate of Ca2+ ion flux through the NCX, as
      well as the NCX currents, were higher in the DO group than in the control group
      in both modes. Increased NCX1 levels may contribute to the establishment of DO
      after PBOO by elevating [Ca2+]i in reverse mode under depolarization, potentially
      inducing cell excitability.

PMID- 29636871
TI  - No indications for platelet activation in acute clinical myocardial or renal
      ischemia/reperfusion injury.
AB  - The pathophysiology of ischemia/reperfusion (I/R) injury is complex and poorly
      understood. Animal studies imply platelet activation as an initiator of the
      inflammatory response upon reperfusion. However, it remains unclear whether and
      how these results translate to clinical I/R. This study evaluates putative
      platelet activation in the context of two forms of clinical I/R (heart valve
      surgery with aortic-cross clamping, n = 39 and kidney transplantation, n = 34).
      The technique of sequential selective arteriovenous (AV) measurements over the
      reperfused organs was applied to exclude the influence of systemic changes
      occurring during surgery while simultaneously maximizing sensitivity. Platelet
      activation and degranulation was evaluated by assessing the expression levels of
      established markers, i.e. RANTES (Regulated on Activation, Normal T Cell
      Expressed and Secreted), beta-thromboglobulin (beta-TG), platelet-derived growth
      factor (PDGF)-BB and CXCL8 (known as interleukin-8), and by employing an in-vitro
      assay that specifically tests for platelet excitability. Moreover, a histological
      analysis was performed by means of CD41 staining. Results show stable RANTES,
      beta-TG, PDGF-BB and CXCL8 AV-concentrations within the first half hour over the
      reperfused organs, suggesting that myocardial and renal I/R are not associated
      with platelet activation. Results from the platelet excitability assay were in
      line with these findings and indicated reduced and stable platelet excitability
      following renal and myocardial reperfusion, respectively. Histological analysis
      yield evidence of platelet marginalization in the reperfused organs. In
      conclusion, results from this study do not support a role for platelet activation
      in early phases of clinical I/R injury.

PMID- 29636872
TI  - Qihuang decoction promotes the recovery of intestinal immune barrier dysfunction
      after gastrectomy in rats.
AB  - OBJECTIVE: This study aims to observe the effect of Qihuang decoction on small
      intestinal mucosal barrier after gastrectomy in rats. MATERIALS AND METHODS: A
      total of 80 Wistar rats were randomly divided into normal group, sham operation
      group, enteral nutrition group (EN) and Qihuang decoction group (EN+QH), there
      were 20 rats in each group. Both the EN group and the EN+QH group underwent
      gastrectomy. Instillation of enteral nutrition in the small intestine was
      performed after operation in the EN group. Instillation of enteral nutrition and
      Qihuang decoction in the small intestine was performed after operation in the
      EN+QH group. Only the abdominal incision and closing was performed in the sham
      operation group without drug and nutritional intervention. The expression levels
      of tight junction proteins in intestinal epithelial cells were determined by
      western blotting method. The sIgA content in different anatomic sites of
      intestinal mucosa was determined by double antibody-PEG radioimmunoassay
      technique. The number of IgA+B cells in different anatomic sites of intestinal
      mucosa was determined by immunohistochemical method. RESULTS: The sIgA content in
      the sham operated group was significantly lower than that of normal group
      (P<0.05). The sIgA content and the number of IgA+B cells in Peyer's patches and
      lamina propria lym-phocytes in the EN+QH group were significantly higher than
      that of EN group (P<0.01, P<0.05). The expression levels of RhoA, Rac1 and Cdc42
      increased in the EN group, and the phosphorylation levels of occludin, claudin-1,
      claudin-5, ZO-1 and ZO-2 also increased in the EN group, while the expression
      levels of non-phosphorylated occluding, claudin-1, claudin-5, ZO-1 and ZO-2
      proteins decreased in the EN group (P<0.01, P<0.05). After treatment of Qihuang
      decoction for 7 days, compared with EN group, the expression levels of RhoA, Rac1
      and Cdc42, and the phosphorylation levels of occludin, claudin-1, claudin-5, ZO-1
      and ZO-2 significantly decreased in the EN+QH group, while the expression levels
      of non-phosphorylated occluding, claudin-1, claudin-5, ZO-1 and ZO-2 proteins
      significantly increased in the EN+QH group (P<0.01, P<0.05). CONCLUSIONS: Qihuang
      decoction can promote the proliferation and differentiation of IgA+B lymphocytes
      and increase the sIgA content in intestinal mucosal immune barrier after
      gastrectomy in rats, it also can promote the expression of tight junction
      proteins to improve the permeability of intestinal mucosa and promote the
      recovery of intestinal immune barrier dysfunction in rats after gastrectomy by
      inhibiting the tight junction associated proteins' phosphorylation induced by
      Rho/ROCK signaling pathway.

PMID- 29636873
TI  - Experimental study on the clinical effects of Xiaoru Sanjie Jiaonang on mammary
      glands hyperplasia and ki-67.
AB  - OBJECTIVE: This study aims to observe the effect and mechanism of Xiaoru Sanjie
      Jiaonang (XRSJ) on the treatment of mammary gland hyperplasia, and provide a
      theoretical basis and clinical evidence for clinical expansion. METHODS: Japanese
      white rabbits were randomly divided into three groups: high-, middle- and low
      dose groups; Xiaoyao Pill group; model control group; normal control group. The
      observation points were as follows: before XRSJ administration, three months
      after XRSJ administration, and three months after XRSJ discontinuance. Changes in
      breast height, morphological changes of the mammary gland under a light and
      electron microscope, and the expression of ki-67 were observed. At the same time,
      patients diagnosed with mammary gland hyperplasia at an Outpatient Clinic were
      selected and divided into treatment groups. These patients received XRSJ and
      Xiaoyao Pills, respectively, for one month, while patients in the control group
      did not receive any drug treatment. Clinical efficacy was observed while
      rechecking at the Outpatient Clinic after three months. Treatment with a
      therapeutic dose of XRSJ could significantly reduce breast height, decrease the
      number of lobules and acini in hyperplastic mammary glands and the layer number
      of ductal glandular epithelial cells, substantially lower the content of serum
      estradiol (E2), significantly downregulate the expression of ki-67 protein in
      mammary tissues, and inhibit mammary gland hyperplasia. CONCLUSION: XRSJ
      treatment can relieve mammary tissue hyperplastic lesions, reduce E2 levels and
      downregulate the expression of ki-67. It has a significant therapeutic effect on
      mammary gland hyperplasia.

PMID- 29636874
TI  - Renal proteomic analysis of RGC-32 knockout mice reveals the potential mechanism
      of RGC-32 in regulating cell cycle.
AB  - This study aimed to investigate the exact function of RGC-32 in kidney diseases
      and explore the potential mechanism of RGC-32 in regulating cell cycle. RGC-32
      knockout (RGC-32-/-) mice were generated from C57BL/6 embryonic stem cells.
      Differentially expressed proteins in the kidney were investigated with the
      isobaric tags for relative and absolute quantification (iTRAQ) technique. Gene
      ontology analyses (GO), Kyoto encyclopedia of genes and genomes (KEGG) pathway
      mapping analysis and functional network analysis were also performed. The
      expressions of Smc3, Smad 2-3, DNA-PK were further confirmed by qPCR. Results
      showed that 4690 proteins were quantified on the basis of 25165 unique peptides.
      Comparative proteomic analysis revealed 361 differentially expressed proteins in
      RGC-32-/- mice (knockout/wild ratio >+/- 1.2 and P<0.05). GO and KEGG pathway
      mapping analyses showed differentially expressed proteins were involved in
      spliceosome, fluid shear stress and atherosclerosis protein processing in
      endoplasmic reticulum, pathways in cancer, viral carcinogenesis, epithelial cell
      signaling in Helicobacter pylori infection, HTLV-I infection, PI3K-Akt signaling
      pathway, ubiquitin mediated proteolysis, Parkinson's disease, MAPK signaling
      pathway, carbon metabolism, Alzheimer's disease, NOD-like receptor signaling
      pathway, tight junction, Proteoglycans in cancer, phagosome, ribosome, mTOR
      signaling pathway, and AMPK signaling pathway. Differentially expressed proteins
      Smc3 (0.821), DNA-PK (0.761), Smad 2-3 (0.631) were involved in cell cycle
      regulation. mRNA expression of Smad2-3, DNA-PK, and Smc3 was consistent with that
      from iTRAQ. It is concluded that RGC-32 may affect the expression of many
      proteins (76 up-regulated and 285 down-regulated) in the kidney, and may regulate
      the expression of Smc3, DNA-PK and Smad 2-3 to affect the cell cycle.

PMID- 29636875
TI  - Cordyceps sinensis may inhibit Th22 cell chemotaxis to improve kidney function in
      lgA nephropathy.
AB  - IgA nephropathy is the most common form of primary glomerulonephritis and an
      important cause of kidney failure. Cordyceps sinensis (CS) is a parasitic fungus
      that has a long history of use in Chinese medicine for the treatment of
      nephritis. Interleukin (IL)-22-producing helper T cells (Th22 cells) have been
      reported to be involved in lgA nephropathy. Th22 cells link the immune response
      to tissue inflammation. To elucidate the possible efficacy and mechanisms by
      which CS counteracts nephritis, we established an IgA nephropathy model in 6-week
      old female BALB/c mice. The mice were randomly separated into 3 groups, the
      normal control, IgA nephropathy and CS (5 mg/kg/d) treatment groups. The Th22
      cell frequencies and the relative pathological and cytokine changes were measured
      with flow cytometry, whereas the serum chemokine ligand 27 (CCL27) and IL-22
      concentrations were detected with ELISA. The Th22 cell frequency decreased after
      1 month of CS therapy. Additionally, mesangial cell proliferation decreased.
      Moreover, the chemokine receptor type 10 (CCR10), CCL27 and IL-22 expression
      levels were significantly reduced. In conclusion, CS may modulate the chemotaxis
      of Th22 cells to suppress inflammatory responses in IgA nephropathy.

PMID- 29636876
TI  - MiR-143-3p suppresses the progression of ovarian cancer.
AB  - MicroRNAs (miRNAs) are a class of naturally occurring, small, non-coding RNAs
      that target protein-coding mRNAs at the post-transcriptional level and
      participate in various biological processes. Our previous studies suggested that
      miR-143-3p functions as a tumor suppressor and has a role in the progression of
      ovarian cancer, in part through the regulation of the tumor promoter. In this
      study, we found that the mRNA expression level of miR-143-3p was significantly
      decreased in ovarian cancer tissues, in comparison with normal ovarian tissues by
      high-throughput miRNA profiling and quantitative RT-PCR. Secondly, we indicated
      that the up-regulation of miR-143-3p in the ovarian cancer cell lines SKOV3, ES2,
      and OVCAR3 significantly reduced their proliferation, migration, and invasion.
      Furthermore, miR-143-3p inhibited the growth of ovarian tumors in vivo in a
      xenograft experiment. In addition, miR-143-3p down-regulated the expression of
      transforming growth factor (TGF)-beta-activated kinase 1 (TAK1) in human ovarian
      cancer cells. Therefore, our study indicates that miR-143-3p inhibited the
      proliferation, migration, and invasion of ovarian cancer cells in vitro, as well
      as ovarian tumorigenesis in vivo. This inhibitory effect may target TAK1,
      suggesting a potential application of the miR-143-3p-TAK1 pathway in the clinical
      diagnosis and treatment of ovarian cancer.

PMID- 29636877
TI  - Effects of talactoferrin alpha on lung adenoma prevention in A/J mice June 2,
      2016.
AB  - Talactoferrin alpha is a promising non-toxic solid tumor cancer agent that met
      with success in the treatment of early-stage lung cancer clinically in humans. It
      is well-tolerated, anddendritic cell-stimulation is a target. We tested the
      efficacy of this agent in a chemoprevention setting in A/J mice. All groups
      received benzo[a]pyrene (B[a]P) by oral gavage in three doses of 3 mg/kg body
      weight over the course of one week. Animals were then randomized into 5 groups of
      24 mice per group based on weight. Experimental diets oftalactoferrin alpha
      (Agennix Inc., Indianapolis, IN), at 1.40% and 0.42% of the diet, were started
      one week or eight weeks after the last dose of B[a]P. Animals were continued on
      the feeding schedule, weighed weekly, and monitored for toxicity. The study was
      concluded 16 weeks after administration of B[a]P. The agent was well-tolerated
      for the duration of the experiment and there was no observable toxicity or weight
      change. The average number of adenomas per animal was 14.04 +/- 0.93 (N=24) in
      the control group, 18.14 +/- 1.45 (N=22) in the early low-dose group, 16.70 +/-
      1.30 (N=23) in the late low-dose group, 15.09 +/- 1.41 (N=23) in the early high
      dose group and 14.46 +/- 1.21 (N=24) in the late high-dose group. We conclude
      talactoferrinalpha is well-tolerated. However, it did not inhibit carcinogenesis
      at a dose of 1.4% or 0.42% of the diet, which equates to human doses of 1.12
      g/kg/day or 0.336 g/kg/day.

PMID- 29636878
TI  - Ubiquitination regulation of inflammatory responses through NF-kappaB pathway.
AB  - The development of inflammation is mutually affected with damaged DNA and the
      abnormal expression of protein modification. Ubiquitination, a way of protein
      modification, plays a key role in regulating various biological functions
      including inflammation responses. The ubiquitin enzymes and deubiquitinating
      enzymes (DUBs) jointly control the ubiquitination. The fact that various
      ubiquitin linkage chains control the fate of the substrate suggests that the
      regulatory mechanisms of ubiquitin enzymes are central for ubiquitination. In
      inflammation diseases, the pro-inflammatory transcription factor NF-kappaB
      regulates transcription of pro-labour mediators in response to inflammatory
      stimuli and expression of numerous genes that control inflammation which is
      associated with ubiquitination. The ubiquitination regulates NF-kappaB signaling
      pathway with many receptor families, including NOD-like receptors (NLR), Toll
      like receptors (TLR) and RIG-I-like receptors (RLR), mainly by K63-linked
      polyubiquitin chains. In this review, we highlight the study of ubiquitination in
      the inflammatory signaling pathway including NF-kappaB signaling regulated by
      ubiquitin enzymes and DUBs. Furthermore, it is emphasized that the interaction of
      ubiquitin-mediated inflammatory signaling system accurately regulates the
      inflammatory responses.

PMID- 29636879
TI  - Differential microRNA expression profiles between young and old lung
      adenocarcinoma patients.
AB  - Lung cancer is the leading cause of cancer-related mortality, and approximately
      80% of cases are non-small cell lung cancer (NSCLC). Recently, the incidence of
      NSCLC has been quickly increasing, while the age of patients at diagnosis is
      decreasing. To date, it is still controversial whether younger patients have
      better or worse outcomes compared with their older counterparts. MicroRNAs
      (miRNAs) have been defined to play a key role in cancer pathogenesis, and their
      aberrant expression has been suggested as a potential biomarker of prognosis in
      lung adenocarcinoma. To understand the molecular features of young and old
      adenocarcinoma patients, we investigated the expression level of a panel of
      miRNAs selected after a mini-literature review. The expression analysis was
      performed by the nCounter System(r) (NanoString Technologies) directly on RNA,
      including small RNAs. The analysis revealed that 7 miRNAs (miR-25-3p, miR-29c-3p,
      miR-33a-5p, miR-144-3p, miR-153-3p, miR-342-5p and miR-485-3p) were
      differentially expressed in the two groups (P<0.05). All of these miRNAs showed
      higher expression levels in young compared to old patients, and their predicted
      targets included EGFR, MET, VEGF-A, TP53 and PDGFRa. miR-144-3p had an opposite
      influence on overall survival since its upregulation was associated with a worse
      prognosis in young patients (P=0.01) and with a better outcome in the older group
      (P=0.03). We observed that lung cancer in young and old patients may be
      influenced by different regulatory mechanisms. Moreover, one of the down
      regulated miRNAs showed a different prognostic impact in the two groups,
      confirming that young and old patients deserve a specific clinical approach.

PMID- 29636880
TI  - Umbilical cord mesenchymal stem cell (UC-MSC) transplantations for cerebral
      palsy.
AB  - This study reports a case of a 4-year-old boy patient with abnormalities of
      muscle tone, movement and motor skills, as well as unstable gait leading to
      frequent falls. The results of the electroencephalogram (EEG) indicate moderately
      abnormal EEG, accompanied by irregular seizures. Based on these clinical
      characteristics, the patient was diagnosed with cerebral palsy (CP) in our
      hospital. In this study, the patient was treated with umbilical cord mesenchymal
      stem cell (UC-MSC) transplantation therapy. This patient received UC-MSC
      transplantation 3 times (5.3*107) in total. After three successive cell
      transplantations, the patient recovered well and showed obvious improvements in
      EEG and limb strength, motor function, and language expression. However, the
      improvement in intelligence quotient (IQ) was less obvious. These results
      indicate that UC-MSC transplantation is a promising treatment for cerebral palsy.

PMID- 29636881
TI  - The arachidonic acid metabolism protein-protein interaction network and its
      expression pattern in esophageal diseases.
AB  - Arachidonic acid (AA) and its metabolites are involved in the development and
      progression of inflammation and tumors in various tissues. We investigated the
      protein-protein interaction network (PPIN) of key enzymes in AA metabolism and
      their interacting proteins, as well as their expression patterns in different
      types of esophageal disease, involving esophagitis, Barrett's esophagus,
      adenocarcinoma and squamous cell carcinoma. PPINs were constructed to illustrate
      the key enzymes and their interacting proteins along the metabolic cascade. The
      network also showed key enzymes that could connect or cross-talk with at least
      one partner protein. The inflammation-related gene RELA (NF-kB) was found to
      interact with both PLA2G4A and ALOX5. Expression levels of the PPIN proteins, as
      well as their expression correlations, in different esophageal diseases were
      analyzed and integrated into the PPIN to illustrate a dynamic change. At least
      six significant pairs of expression relationships were identified across
      different esophageal diseases. The expression levels of eight enzymes (ALOX5,
      ALOX5AP, CYP2C8, CYP4F11, LTA4H, PLA2G4A, CYP2D6, PTGES2) correlated with the
      survival time of ESCC patients. In summary, we constructed an AA metabolic PPIN
      to explore AA metabolism-related gene expression patterns in esophageal diseases,
      showing their dynamic change and potential for therapeutic targeting from
      inflammation to cancer.

PMID- 29636882
TI  - Quantitative magnetic resonance imaging for diagnosis of intervertebral disc
      degeneration of the cervico-thoracic junction: a pilot study.
AB  - This study aimed to appraise two quantitative magnetic resonance imaging
      techniques, T2* imaging and diffusion-weighted imaging (DWI), for the diagnosis
      of the intervertebral disc degeneration of the cervico-thoracic junction.
      Influence of specific factors and diagnostic accuracy of both techniques were
      particularly explored. Sixty-one volunteers with neck and upper back pain were
      recruited and evaluated with both T2* imaging and DWI. The Pfirrmann grade, T2*
      relaxation time and apparent diffusion coefficient (ADC) value of each disc
      between C7 and T3 were recorded. Stratified analyses were performed for different
      anatomic levels, genders, age ranges and Pfirrmann grades. The diagnostic
      accuracy of both techniques was investigated using the receiver operating
      characteristic (ROC) curves. No statistically significant difference of either
      T2* relaxation time or ADC value was detected between males and females. Both
      parameters decreased with the increasing age and Pfirrmann grade. The ROC curves
      showed the higher sensitivity and specificity for T2* imaging than DWI to
      quantitatively identify the disc degeneration. Particularly, T2* imaging allowed
      for a quantitative distinguishing the normal, mild and moderate disc degeneration
      from the severe degeneration, which was unable to accomplish with DWI. In
      conclusion, we demonstrated that T2* imaging possess a better accuracy than DWI
      to quantitatively diagnose the intervertebral disc degeneration at the cervico
      thoracic junction.

PMID- 29636883
TI  - The embryonic transcription factor Brachyury confers chordoma chemoresistance via
      upregulating CA9.
AB  - Being a rare malignant bone tumor on the axial skeleton, chordoma is locally
      invasive and has a high rate of recurrence. Despite extensive studies, the
      mechanisms of chordoma recurrence after surgical intervention, as well as
      resistance to radiation and chemotherapy, remain elusive. In this study, primary
      chordoma cell lines PCH1 and PCH2 were established and characterized by chordoma
      specific markers. We found that the embryonic transcription factor Brachyury
      inhibits Paclitaxel induced apoptosis in different cells, including PCH1 and U2OS
      cells. T gene regulated genes were identified in PCH1 and U2OS using microarray.
      After comparing gene regulated by Brachyury in different cells and the chromatin
      immunoprecipitation assay, we identified carbonic anhydrase IX (CA9) as a common
      target gene of Brachyury. Besides, immunohistochemical staining of CA9 and
      Brachyury in chordoma tissues revealed that their expression levels were
      positively correlated. We further showed that CA9 is responsible for Paclitaxel
      resistance in PCH1 cell. Our data suggest that CA9 plays a role in Brachyury
      mediated Paclitaxel resistance and serves as a potential target for chordoma
      treatment.

PMID- 29636884
TI  - Low-intensity pulsed ultrasound suppresses proliferation and promotes apoptosis
      via p38 MAPK signaling in rat visceral preadipocytes.
AB  - Low-intensity pulsed ultrasound (LIPUS) has been used widely in clinical therapy
      for bone fracture and soft tissue injury. However, whether LIPUS regulates
      primary preadipocyte function and adipogenesis remains unknown. In this study, we
      investigated the potential role of LIPUS in regulating visceral preadipocyte
      function. Resuspended rat visceral preadipocytes were treated with LIPUS (0.5
      MHz, 109.44 mW/cm2) for 1 min and then cultured for an additional 48 hours. Cell
      proliferation was examined using the CCK-8 assay, and the early apoptosis rate
      was determined by flow cytometry. In addition, we evaluated the related signaling
      pathway via examination of proliferating cell nuclear antigen (PCNA), peroxisome
      proliferator-activated receptor gamma (PPARgamma), Bcl2, Bax, cleaved caspase 3
      (C-C3), and mitogen-activated protein kinase (MAPK) member protein levels using
      western blot or quantitative real-time PCR (qRT-PCR). LIPUS inhibited
      preadipocyte proliferation and induced cell apoptosis. The protein expression of
      proliferation markers decreased, while expression of the apoptosis-related
      modulators increased following LIPUS treatment. LIPUS treatment decreased
      extracellular signal-regulated kinase (ERK) phosphorylation and increased p38
      MAPK phosphorylation. Inhibition of p38 MAPK rescued the LIPUS-induced
      proliferation inhibition and apoptosis induction. Thus, treatment of rat visceral
      preadipocytes with 0.5 MHz LIPUS suppresses proliferation and promotes apoptosis
      via activation of p38 MAPK signaling.

PMID- 29636885
TI  - Protective role of puerarin on LPS/D-Gal induced acute liver injury via restoring
      autophagy.
AB  - Acute liver injury is a destructive liver disorder resulting from overwhelming
      liver inflammation, oxidative stress and hepatocyte death. Puerarin is a natural
      flavonoid compound isolated from the traditional Chinese herb radix puerariae.
      This study investigated the protective effects of puerarin against
      lipopolysaccharide (LPS)/D-galactosamine (D-Gal)-induced liver injury and the
      potential mechanisms in mice. Mice were given an intraperitoneal administration
      of puerarin 200 mg/kg 2 h prior to LPS (50 MUg/kg)/D-Gal (400 mg/kg) injection
      and were sacrificed 6 h post LPS/D-Gal treatment. The results showed that
      administration of puerarin substantially alleviated LPS/D-Gal-induced acute liver
      injury in mice by increased survival rates, improved liver histopathology,
      reduced plasma alanine aminotransferase (ALT) and aspartate aminotransferase
      (AST) levels, alleviated production of pro-inflammatory cytokines, and suppressed
      hepatocyte apoptosis. Moreover, puerarin pretreatment activated autophagy by
      increased the ratio of LC3B-II/I and the protein levels of Beclin-1, decreased
      the levels of p62 protein expression. Taken together, these findings demonstrated
      that puerarin could prevent the LPS/D-Gal-induced liver injury in mice, and its
      mechanisms might be associated with the increments of autophagy and suppression
      of apoptosis.

PMID- 29636887
TI  - Advanced maternal age impairs spatial learning capacity in young adult mouse
      offspring.
AB  - Effects of maternal aging on the offspring cognitive function remain
      controversial in population-based investigations, and information available in
      animal studies is very limited. We investigated the impact of a delayed first
      natural pregnancy on pregnancy outcomes in the mouse model. Spatial learning
      capacity in young adult mouse offspring was observed by step-down passive
      avoidance task and Morris water maze (MWM). Maternal serum alpha-klotho was
      measured by ELISA. Morphological characteristics of fetoplacental unit and
      offspring brain were identified by H&E and immunohistochemistry. Klotho, VDR and
      other related genes expression were quantified by real-time-RT-PCR and western
      blot. We found delayed pregnancy reduced fertility in female mice by three-fold
      (Young vs. Old: 5.0% vs. 20.7%), and increased adverse pregnant outcomes by eight
      fold (Young vs. Old: 3.0% vs. 27.5%). Mice born to old mothers exhibited shorter
      retention trial latency in passive avoidance task and longer latency to find the
      platform in MWM, suggesting worse performance on the tests that measure learning
      and memory. Serum alpha-klotho level was lower in old female mice before
      pregnancy, whereas became comparable after pregnancy. Vitamin D receptor (VDR)
      expression, both in mRNA and protein, markedly decreased during the early stage
      of fetoplacental unit in old mice, especially in trophoblast giant cells when
      compared with that of young mice. Importantly, consistent with fetoplacental
      unit, VDR expression also declined in hippocampus from offspring born to old
      mice. These results suggest that young adult offspring from aged mothers
      exhibited worse cognitive function and the reduced VDR expression during
      fetoplacental development might play an important role.

PMID- 29636886
TI  - COX-2 contributes to LPS-induced Stat3 activation and IL-6 production in
      microglial cells.
AB  - Many stimuli including lipopolysaccharide (LPS) could activate microglial cells
      to subsequently cause inflammatory nerve injury. However, the mechanism of LPS
      induced neuroinflammation in microglial cells is still elusive. Thus, the present
      study was undertaken to examine the role of COX-2 in mediating the activation of
      Stat3 and the production of IL-6 in BV2 cells challenged with LPS. After 24 h
      treatment, LPS dose-dependently enhanced COX-2 expression at both mRNA and
      protein levels. Meanwhile, IL-6 with other inflammatory cytokines including IL
      1beta, TNF-alpha, and MCP-1 were similarly enhanced by LPS. Then a specific COX-2
      inhibitor (NS-398) was administered to BV2 before LPS treatment. Significantly,
      COX-2 inhibition suppressed the upregulation of IL-6 at both mRNA and protein
      levels in line with the trend blockade on IL-1beta, TNF-alpha, and MCP-1. Stat3
      drives proinflammatory signaling pathways and contributes to IL-6 production via
      a transcriptional mechanism in many diseases. Here we found that inhibition of
      COX-2 entirely blocked LPS-induced Stat3 phosphorylation, which might contribute
      to the blockade of IL-6 production to some extent. Meanwhile, COX-2 siRNA
      approach largely reproduced the phenotypes shown by specific COX-2 inhibitor in
      LPS-treated BV2 cells. Together, these findings suggested that COX-2 might
      contribute to LPS-induced IL-6 production possibly through activating Stat3
      signaling pathway in microglial cells.

PMID- 29636888
TI  - MicroRNA-134-5p promotes high glucose-induced podocyte apoptosis by targeting bcl
      2.
AB  - Podocyte apoptosis is a typical early feature of diabetic nephropathy (DN), with
      loss of nephrin integrity contributing to increased proteinuria in patients with
      DN. Emerging evidence shows that microRNAs (miRNAs) play vital roles in the
      pathogenesis of DN. Thus, we aimed to further elucidate the role of miRNAs in
      podocyte apoptosis in DN. We used db/db and db/m mice maintained under a
      continuous feeding regime for 12 weeks. Using microarray analysis, we found
      several miRNAs potentially related to podocyte apoptosis. In addition, we
      cultured a conditionally immortalized human podocyte cell line in 30 mM D-glucose
      and found that miR-134-5p was upregulated in both db/db mice and high-glucose
      (HG)-treated podocytes. Upregulation of miR-134-5p was accompanied by podocyte
      apoptosis and downregulation of nephrin. Inhibition of miR-134-5p produced the
      opposite effect. Dual-luciferase reporter assays showed that miR-134-5p directly
      targeted the 3'-untranslated region of the B-cell lymphoma-2 gene (BCL2), and
      further study confirmed an increase in bcl-2 protein level in HG-treated
      podocytes transfected with anti-miR-134-5p. Knockdown of BCL2 impeded the
      antiapoptotic effect of anti-miR-134-5p. Finally, we found that miR-134-5p might
      regulate apoptosis in db/db mice and podocytes by targeting BCL2. Taken together,
      our findings suggest that miR-134-5p promotes podocyte apoptosis under HG
      conditions by targeting BCL2. Our study provides a meaningful approach to
      interpret the mechanisms of action of miRNAs involved in DN.

PMID- 29636889
TI  - Effect of TEAD4 on multilineage differentiation of muscle-derived stem cells.
AB  - TEAD4 is a member of transcriptional enhancer factor (TEF) family of
      transcription factors and plays a pivotal role in regulating embryonic
      development and muscle regeneration. Known previously, dysfunction of TEAD4 in
      mouse myoblasts impairs myotube development. However, the effects of TEAD4 on
      multipotency of muscle-derived stem cells (MDSCs) have not been clearly
      understood. Recently, bovine MDSCs (bMDSCs) were successfully isolated from adult
      bovine muscle. Our derived bMDSCs could differentiate into mesodermal cells,
      including myotubes, adipocytes, and osteoid cells. Our results also revealed that
      bMDSCs had the capacity to develop into ectodermal and endodermal lineages
      including neuron-like cells and insulin-secreting cells. After TEAD4 knock-down
      (TEAD4-KD), bMDSCs still kept the original capacity to differentiate into neuron
      like cells and insulin-secreting cells, as shown by acquisition of both neuronal
      and pancreatic markers normally expressed in differentiated cells. However, up
      regulation of CAV3 and betaMHC failed during myogenesis of bMDSCs with TEAD4-KD,
      although TEAD4-KD in bMDSCs did not affect osteoid cells and myotube formation.
      More interestingly, adipogenic differentiation of TEAD4-KD bMDSCs was
      significantly suppressed. During adipogenic differentiation, TEAD4-KD
      systematically impaired upregulation of TEAD1, TEAD2, and TEAD3, as well as the
      activation of C/EBP2, ADD1, and PPARgamma as the key transcription factors for
      adipogenic differentiation. Finally, TEAD4-KD led to the failure of adipogenesis
      from bMDSCs. Together, our results support that TEAD4 is essential during
      adipogenic differentiation of bMDSCs. It has little effect on myogenesis of
      bMDSCs, and does not affect ostegenesis, neurogenesis, or pancreatic
      differentiation of bMDSCs. Our findings will be helpful for future study on the
      roles of the TEAD family during differentiation of MDSCs, and for controlling
      MDSC differentiation for stem cell applications.

PMID- 29636890
TI  - Paeoniflorin exerts protective effect on radiation-induced hepatic fibrosis in
      rats via TGF-beta1/Smads signaling pathway.
AB  - AIM: This study aimed to investigate the protective effects of paeoniflorin (PAE)
      on radiation-induced hepatic fibrosis in a rat model. METHODS: Fifty healthy male
      Sprague-Dawley rats were randomly assigned to normal control group, hepatic
      fibrosis group, and PAE treatment groups. X-ray exposure was employed to
      establish radiation-induced hepatic fibrosis model. PAE was administered once
      daily, and rats were sacrificed at week 26 after irradiation. The liver
      histopathology was evaluated under a light microscope after HE staining and
      Masson staining. Meanwhile, the protein expression of transforming growth factor
      beta 1 (TGF-beta1), Smad3/4 and Smad7 was detected by immunohistochemistry.
      RESULTS: Radiation-induced liver damage and collagen deposition were observed in
      the model group as compared to normal control group, but PAE treatment
      significantly attenuated the liver injury and reduce collagen deposition (P<0.05
      or 0.01). The hepatic hydroxyproline content and serum levels of TGF-beta1,
      hyaluronic acid, ro-collagen type III and laminin markedly increased in model
      group as compared to control group (P<0.01), but they decreased dramatically
      after PAE treatment. The expression of TGF-beta1, Smad3/4 and Smad7 in the liver
      increased significantly in model group as compared to control group (P<0.01), and
      PAE could down-regulate the expression of Smad3/4 and up-regulate Smad7
      expression (P<0.05 or 0.01). The activities of serum amino-transferase and
      aspartate aminotransferase were significantly higher in hepatic fibrosis group
      than in normal control group, but PAE treatment markedly reduced them (P<0.05).
      CONCLUSION: PAE can inhibit the radiation induced hepatic fibrosis via regulating
      TGF-beta1/Smads signaling pathway.

PMID- 29636891
TI  - Comprehensive analysis of differentially expressed non-coding RNAs and mRNAs in
      gastric cancer cells under hypoxic conditions.
AB  - Hypoxia commonly occurs in solid cancers, especially in gastric cancer due to its
      rapid growth. The ability of gastric cancer cells to survive and progress under
      hypoxic conditions has been known for decades, but the mechanisms underlying this
      characteristic remain poorly understood. As cancer cells undergo changes in their
      genetic profile under certain conditions, we investigated the expression profile
      of non-coding RNAs (circRNAs, lncRNAs, and miRNAs) and mRNAs in gastric cancer
      MKN-28 cells under hypoxic conditions via sequencing and subsequent bioinformatic
      analyses. In addition, quantitative reverse transcription polymerase chain
      reaction (qRT-PCR) was used to validate the results. We identified a number of
      significantly differentially expressed circRNAs, lncRNAs, miRNAs, and mRNAs in
      hypoxia-exposed MKN-28 cells relative to the normoxia control, and results of qRT
      PCR were consistent with sequencing data. Pathway enrichment analyses revealed
      the principal functions of the significantly deregulated genes. Furthermore,
      examination of co-expression and competing endogenous RNA (ceRNAs) networks
      illustrated the complex regulatory pathways among non-coding RNAs and mRNAs,
      implicating these pathways in gastric cancer. In conclusion, our findings provide
      a novel perspective on non-coding RNAs and mRNAs and lay the foundation for
      future research on the potential roles of non-coding RNAs in gastric cancer under
      hypoxic conditions.

PMID- 29636892
TI  - Extracorporeal shock wave markedly alleviates radiation-induced chronic cystitis
      in rat.
AB  - This study tested the hypothesis that extracorporeal shock wave (ECSW) treatment
      can effectively inhibit radiation-induced chronic cystitis (CC). Adult male
      Sprague-Dawley (SD) rats (n = 24) were randomly divided into group 1 (normal
      control), group 2 (CC induced by radiation with 300 cGy twice with a four-hour
      interval to the urinary bladder), group 3 [CC with ECSW treatment (0.2 mJ/mm2/120
      impulses/at days 1, 7, and 14 after radiation)]. Bladder specimens were harvested
      by day 28 after radiation. By day 28 after radiation, the degree of detrusor
      contraction impairment was significantly higher in group 2 than that in groups 1
      and 3, and significantly higher in group 3 than that in group 1 (P<0.0001). The
      urine albumin concentration expressed an opposite pattern compared to that of
      detrusor function among the three groups (P<0.0001). The bladder protein
      expressions of inflammatory (TLR-2/TLR-4/IL-6/IL-12/MMP-9/TNF-alpha/NF
      kappaB/RANTES/iNOS) and oxidative-stress (NOX-1/NOX-2/oxidized protein)
      biomarkers exhibited a pattern identical to that of urine albumin in all groups
      (all P<0.0001). The cellular expressions of inflammatory (CD14+/CD68+/CD74+/COX
      2/MIF+/substance P+) and cytokeratin (CK13+/HMW CK+/CK+17/CK+18/CK+19)
      biomarkers, and collagen-deposition/fibrotic areas as well as epithelial-damaged
      score displayed an identical pattern compared to that of urine albumin among the
      three groups (all P<0.0001). In conclusion, ECSW treatment effectively protected
      urinary bladder from radiation-induced CC.

PMID- 29636893
TI  - A 3D-printed passive ultrasound phase-interference compensator for reduced wave
      degradation in cancellous bone - an experimental study in replica models.
AB  - The current 'active' solution to overcome the impediment of ultrasound wave
      degradation associated with transit-time variation in complex tissue structures,
      such as the skull, is to vary the transmission delay of ultrasound pulses from
      individual transducer elements. This article considers a novel 'passive' solution
      in which constant transit time is achieved by propagating through an additional
      material layer positioned between the ultrasound transducer and the test sample.
      To test the concept, replica models based on four cancellous bone natural tissue
      samples and their corresponding passive ultrasound phase-interference compensator
      were 3D-printed. Normalised broadband ultrasound attenuation was used as a
      quantitative measure of wave degradation, performed in transmission mode at a
      frequency of 1 MHz and yielding a reduction ranging from 57% to 74% when the
      ultrasound phase-interference compensator was incorporated. It is suggested that
      the passive compensator offers a broad utility and, hence, it may be applied to
      any ultrasound transducer, of any complexity (single element or array), frequency
      and dimension.

PMID- 29636894
TI  - A temporal examination of calcium signaling in cancer- from tumorigenesis, to
      immune evasion, and metastasis.
AB  - Background: Although the study of calcium (Ca2+) is classically associated with
      excitable cells such as myocytes or neurons, the ubiquity of this essential
      element in all cellular processes has led to interest in other cell types. The
      importance of Ca2+ to apoptosis, cell signaling, and immune activation is of
      special import in cancer. Main: Here we review the current understanding of Ca2+
      in each of these processes vital to the initiation, spread, and drug resistance
      of malignancies. We describe the involvement of Ca2+, and Ca2+ related proteins
      in cell cycle checkpoints and Ca2+ dependent apoptosis and discuss their roles in
      cellular immortalization. The role of Ca2+ in inter-cellular communication is
      also discussed in relevance to tumor-stromal communication, angiogenesis, and
      tumor microinvasion. The role that Ca2+ plays in immune surveillance and evasion
      is also addressed. Finally, we discuss the possibility of targeting Ca2+ singling
      to address the most pressing topics of cancer treatment: metastatic disease and
      drug resistance. Conclusion: This review discusses the current understanding of
      Ca2+ in cancer. By addressing Ca2+ facilitated angiogenesis, immune evasion,
      metastasis, and drug resistance, we anticipate future avenues for development of
      Ca2+ as a nexus of therapy.

PMID- 29636896
TI  - Case Report: Mucus plug in bronchus mimicking a bronchial solid foreign body
      obstruction.
AB  - Bronchial foreign body obstruction is common in all clinical settings.
      Obstruction of the airway due to foreign bodies and foreign body aspiration are
      major causes of childhood mortality and morbidity, which are a big challenge to
      manage. Occasionally, bronchial obstruction may be due to mucus plugs or other
      endogenous factors. Here we describe a case of bronchial obstruction caused by
      mucus plug formation that was managed conservatively in a one-year old boy. The
      patient was suffering from a cough and noisy breathing for 2 days prior to coming
      to our hospital, when he experienced sudden onset of difficulty in breathing and
      a severe cough. At the time of presentation his vital sign readings were:- HR 186
      bpm, RR 46/min, BP 78/40 MmHg, temp 36.9 degrees C and SPO2 68%. He was given
      oxygen immediately and nebulization was started. Chest CT scan was performed that
      suggested the presence of a right bronchial foreign body with right sided
      obstructive emphysema. The patient was stable with oxygenation and nebulization
      with ipratropium bromide, albuterol, normal saline and budesonide before the CT
      scan. Therefore, we conclude that symptoms resembling foreign body obstruction
      are not always aspirated or inhaled, and sometimes secreted sputum forms a plug,
      which mimics the symptoms of foreign body obstruction.

PMID- 29636897
TI  - Monocytes isolated by positive and negative magnetic sorting techniques show
      different molecular characteristics and immunophenotypic behaviour.
AB  - Background: Magnetic sorting of cells, based on  microbead conjugated antibodies
      (Abs), employs positive as well as negative immunomagnetic separation methods,
      for isolation of a specific cell population. These microbeads are suggested to be
      nontoxic, biodegradable carriers conjugated to various antibodies. Isolation of
      cells through positive selection involves the attachment of antibody conjugated
      microbeads to the cells of interest, followed by their isolation in the presence
      of a strong magnetic field to obtain higher purity. Negative selection involves
      attachment of microbead conjugated antibodies to all other cell populations
      except the cells of interest, which remain untagged. In the present study, we
      compared the two methods for their effect on functional and immunophenotypic
      behavior of isolated CD14+ monocytes. Methods: Peripheral blood mononuclear cells
      (PBMCs) were isolated from blood collected from healthy volunteers by density
      gradient centrifugation. Human blood derived monocytes were isolated through
      positive selection and negative selection, making use of the appropriate monocyte
      isolation kit. Monocytes were then stimulated with lipopolysaccharide (LPS) and
      their activation and proliferation capacity were examined. The degradation or
      dissociation of cell-bound microbeads was also investigated. Results: We observed
      an impaired LPS sensitivity as well as poor activation and proliferation capacity
      upon stimulation by LPS in positively sorted CD14+ monocytes as compared to
      negatively sorted CD14+ monocytes. The attached microbeads did not degrade and
      remained attached to the cells even after 6 days of culture. Conclusions: Our
      results suggest that positively sorted CD14+ cells exhibit hampered functionality
      and may result in inaccurate analysis and observations in downstream
      applications. However, these cells can be used for immediate analytical
      procedures.

PMID- 29636895
TI  - Pollen and spore monitoring in the world.
AB  - Background: Ambient air quality monitoring is a governmental duty that is widely
      carried out in order to detect non-biological ("chemical") components in ambient
      air, such as particles of < 10 um (PM10, PM2.5), ozone, sulphur dioxide, and
      nitrogen oxides. These monitoring networks are publicly funded and air quality
      data are open to the public. The situation for biological particles that have
      detrimental effects on health, as is the case of pollen and fungal spores, is
      however very different. Most pollen and spore monitoring networks are not
      publicly funded and data are not freely available. The information regarding
      which biological particle is being monitored, where and by whom, is consequently
      often not known, even by aerobiologists themselves. This is a considerable
      problem, as local pollen data are an important tool for the prevention of
      allergic symptoms. Objective: The aim of this study was to review pollen
      monitoring stations throughout the world and to create an interactive
      visualization of their distribution. Methods: The method employed to collect
      information was based on: (a) a review of the recent and historical bibliography
      related to pollen and fungal spore monitoring, and (b) personal surveys of the
      managers of national and regional monitoring networks. The interactive
      application was developed using the R programming language. Results: We have
      created an inventory of the active pollen and spore monitoring stations in the
      world. There are at least 879 active pollen monitoring stations in the world,
      most of which are in Europe (> 500). The prevalent monitoring method is based on
      the Hirst principle (> 600 stations). The inventory is visualised as an
      interactive and on-line map. It can be searched, its appearance can be adjusted
      to the users' needs and it is updated regularly, as new stations or changes to
      those that already exist can be submitted online. Conclusions: The map shows the
      current situation of pollen and spore monitoring and facilitates collaboration
      among those individuals who are interested in pollen and spore counts. It might
      also help to improve the monitoring of biological particles up to the current
      level employed for non-biological components.

PMID- 29636898
TI  - Matchmaking in Bioinformatics.
AB  - Ever return from a meeting feeling elated by all those exciting talks, yet unsure
      how all those presented glamorous and/or exciting tools can be useful in your
      research?  Or do you have a great piece of software you want to share, yet only a
      handful of people visited your poster? We have all been there, and that is why we
      organized the Matchmaking for Computational and Experimental Biologists Session
      at the latest ISCB/GLBIO'2017 meeting in Chicago (May 15-17, 2017). The session
      exemplifies a novel approach, mimicking "matchmaking", to encouraging
      communication, making connections and fostering collaborations between
      computational and non-computational biologists. More specifically, the session
      facilitates face-to-face communication between researchers with similar or
      differing research interests, which we feel are critical for promoting productive
      discussions and collaborations.  To accomplish this, three short scheduled talks
      were delivered, focusing on RNA-seq, integration of clinical and genomic data,
      and chromatin accessibility analyses.  Next, small-table developer-led
      discussions, modeled after speed-dating, enabled each developer (including the
      speakers) to introduce a specific tool and to engage potential users or other
      developers around the table.  Notably, we asked the audience whether any other
      tool developers would want to showcase their tool and we thus added four
      developers as moderators of these small-table discussions.  Given the positive
      feedback from the tool developers, we feel that this type of session is an
      effective approach for promoting valuable scientific discussion, and is
      particularly helpful in the context of conferences where the number of
      participants and activities could hamper such interactions.

PMID- 29636899
TI  - archiDART v3.0: A new data analysis pipeline allowing the topological analysis of
      plant root systems.
AB  - Quantifying plant morphology is a very challenging task that requires methods
      able to capture the geometry and topology of plant organs at various spatial
      scales. Recently, the use of persistent homology as a mathematical framework to
      quantify plant morphology has been successfully demonstrated for leaves, shoots,
      and root systems. In this paper, we present a new data analysis pipeline
      implemented in the R package archiDART to analyse root system architectures using
      persistent homology. In addition, we also show that both geometric and
      topological descriptors are necessary to accurately compare root systems and
      assess their natural complexity.

PMID- 29636900
TI  - How to prevent the next Marathon Pharmaceuticals.
AB  - In recent years, several drug companies have exploited U.S. regulatory policies
      to acquire exclusive rights to cheap therapies and substantially raise their
      prices, and Federal agencies and state governments are exploring various ways to
      prevent or punish such behavior in the future. Among these cases, however,
      Marathon Pharmaceuticals' handling of Emflaza (deflazacort) is unique, because
      the drug was previously only available abroad, and was never previously sold in
      the U.S. before the company obtained FDA approval for it. Thus, laws and policies
      designed to address price hikes on already-marketed drugs are unlikely to prevent
      additional Marathon-like scenarios. In this article, we describe in more detail
      the unique features of Emflaza compared with these other recent cases of drug
      price increases, determine the likelihood that similar situations will arise in
      the future, and explore legislative and administrative options to specifically
      prevent such behavior.

PMID- 29636901
TI  - Case Report: III degrees  atrioventricular block due to fulminant myocarditis
      managed with non-invasive transcutaneous pacing.
AB  - Fulminant myocarditis is a life-threatening clinical condition. It is the
      inflammation of myocardium leading to acute heart failure, cardiogenic shock and
      cardiac arrhythmias. Incidence of fulminant myocarditis is low and mortality is
      high. Most grievous complications of fulminant myocarditis is mainly cardiac
      arrhythmias; if there is delay on active management of the patient, it may be
      fatal. Here, we describe a case of III degrees  atrioventricular block due to
      fulminant myocarditis that was managed with non-invasive transcutaneous cardiac
      pacing in the absence of ECMO. The non-invasive transcutaneous pacemaker is a
      safe, effective and convenient device to revert arrhythmias.

PMID- 29636902
TI  - Using electronic biology based platform to predict flu vaccine efficacy for
      2018/2019.
AB  - Flu epidemics and potential pandemics pose great challenges to public health
      institutions, scientists and vaccine producers. Creating right vaccine
      composition for different parts of the world is not trivial and has been
      historically very problematic. This often resulted in decrease in vaccinations
      and reduced trust in public health officials. To improve future protection of
      population against flu we urgently need new methods for vaccine efficacy
      prediction and vaccine virus selection.

PMID- 29636903
TI  - Recent advances in managing tricuspid regurgitation.
AB  - Isolated tricuspid valve surgery is usually carried out with very high morbidity
      and mortality given the complexity of the affected patients. In light of this,
      trans-catheter tricuspid valve interventions have been emerging as an attractive
      alternative to surgery over the last few years. Although feasibility has been
      shown with a number of devices, clinical experience remains preliminary and
      associated with significant clinical and technical challenges. Here we describe
      currently available trans-catheter treatment options for severe tricuspid
      regurgitation implanted in different locations.

PMID- 29636904
TI  - New perspectives in the treatment of body dysmorphic disorder.
AB  - Body dysmorphic disorder (BDD) is a disabling illness with a high worldwide
      prevalence. Patients demonstrate a debilitating preoccupation with one or more
      perceived defects, often marked by poor insight or delusional convictions.
      Multiple studies have suggested that selective serotonin reuptake inhibitors and
      various cognitive behavioral therapy modalities are effective first-line
      treatments in decreasing BDD severity, relieving depressive symptoms, restoring
      insight, and increasing quality of life. Selective serotonin reuptake inhibitors
      have also recently been shown to be effective for relapse prevention. This review
      provides a comprehensive summary of the current understanding of BDD, including
      its clinical features, epidemiology, genetics, and current treatment modalities.
      Additional research is needed to fully elucidate the relationship between BDD and
      comorbid illnesses such as obsessive-compulsive-related disorders and depression
      and to develop therapies for refractory patients and those who have
      contraindications for pharmacological intervention.

PMID- 29636906
TI  - Hazard and risk assessment strategies for nanoparticle exposures: how far have we
      come in the past 10 years?
AB  - Nanotechnology is an emerging, cross-disciplinary technology designed to create
      and synthesize new materials at the nanoscale (generally defined as a particle
      size range of <=10 -9 meters) to generate innovative or altered material
      properties. The particle properties can be modified to promote different and more
      flexible applications, resulting in consumer benefits, particularly in medical,
      cosmetic, and industrial applications. As this applied science matures and
      flourishes, concerns have arisen regarding potential health effects of exposures
      to untested materials, as many newly developed products have not been adequately
      evaluated. Indeed, it is necessary to ensure that societal and commercial
      advantages are not outweighed by potential human health or environmental
      disadvantages. Therefore, a variety of international planning activities or
      research efforts have been proposed or implemented, particularly in the European
      Union and United States, with the expectation that significant advances will be
      made in understanding potential hazards related to exposures in the occupational
      and/or consumer environments. One of the first conclusions reached regarding
      hazardous effects of nanoparticles stemmed from the findings of early pulmonary
      toxicology studies, suggesting that lung exposures to ultrafine particles were
      more toxic than those to larger, fine-sized particles of similar chemistry. This
      review documents some of the conceptual planning efforts, implementation
      strategies/activities, and research accomplishments over the past 10 years or so.
      It also highlights (in this author's opinion) some shortcomings in the research
      efforts and accomplishments over the same duration. In general, much progress has
      been made in developing and implementing environmental, health, and safety
      research-based protocols for addressing nanosafety issues. However, challenges
      remain in adequately investigating health effects given 1) many different
      nanomaterial types, 2) various potential routes of exposure, 3) nanomaterial
      characterization issues, 4) limitations in research methodologies, such as time
      course and dose-response issues, and 5) inadequate in vitro methodologies for in
      vivo standardized, guideline toxicity testing.

PMID- 29636905
TI  - Recent advances in cardiac catheterization for congenital heart disease.
AB  - The field of pediatric and adult congenital cardiac catheterization has evolved
      rapidly in recent years. This review will focus on some of the newer endovascular
      technological and management strategies now being applied in the pediatric
      interventional laboratory. Emerging imaging techniques such as three-dimensional
      (3D) rotational angiography, multi-modal image fusion, 3D printing, and
      holographic imaging have the potential to enhance our understanding of complex
      congenital heart lesions for diagnostic or interventional purposes. While
      fluoroscopy and standard angiography remain procedural cornerstones, improved
      equipment design has allowed for effective radiation exposure reduction
      strategies. Innovations in device design and implantation techniques have enabled
      the application of percutaneous therapies in a wider range of patients,
      especially those with prohibitive surgical risk. For example, there is growing
      experience in transcatheter duct occlusion in symptomatic low-weight or premature
      infants and stent implantation into the right ventricular outflow tract or
      arterial duct in cyanotic neonates with duct-dependent pulmonary circulations.
      The application of percutaneous pulmonary valve implantation has been extended to
      a broader patient population with dysfunctional 'native' right ventricular
      outflow tracts and has spurred the development of novel techniques and devices to
      solve associated anatomic challenges. Finally, hybrid strategies, combining
      cardiosurgical and interventional approaches, have enhanced our capabilities to
      provide care for those with the most complex of lesions while optimizing efficacy
      and safety.

PMID- 29636907
TI  - Rett syndrome from bench to bedside: recent advances.
AB  - Rett Syndrome is a severe neurological disorder mainly due to de novo mutations
      in the methyl-CpG-binding protein 2 gene ( MECP2). Mecp2 is known to play a role
      in chromatin organization and transcriptional regulation. In this review, we
      report the latest advances on the molecular function of Mecp2 and the new animal
      and cellular models developed to better study Rett syndrome. Finally, we present
      the latest innovative therapeutic approaches, ranging from classical pharmacology
      to correct symptoms to more innovative approaches intended to cure the pathology.

PMID- 29636908
TI  - Epidemiological, behavioural, and clinical factors associated with antimicrobial
      resistant gonorrhoea: a review.
AB  - Antimicrobial-resistant Neisseria gonorrhoeae is a global public health problem
      in the 21st century. N. gonorrhoeae has developed resistance to all classes of
      antibiotics used for empirical treatment, and clinical treatment failure caused
      by extensively resistant strains has been reported. Identifying specific factors
      associated with an increased risk of antimicrobial-resistant N. gonorrhoeae might
      help to develop strategies to improve antimicrobial stewardship. In this review,
      we describe the findings of 24 studies, published between 1989 and 2017, that
      examined epidemiological, behavioural, and clinical factors and their
      associations with a range of antimicrobial agents used to treat gonorrhoea.
      Antimicrobial-resistant N. gonorrhoeae is more common in older than younger
      adults and in men who have sex with men compared with heterosexual men and women.
      Antimicrobial-resistant N. gonorrhoeae is less common in some black minority and
      Aboriginal ethnic groups than in the majority white population in high-income
      countries. The factors associated with antimicrobial-resistant gonorrhoea are not
      necessarily those associated with a higher risk of gonorrhoea.

PMID- 29636909
TI  - A world without bacterial meningitis: how genomic epidemiology can inform
      vaccination strategy.
AB  - Bacterial meningitis remains an important cause of global morbidity and
      mortality. Although effective vaccinations exist and are being increasingly used
      worldwide, bacterial diversity threatens their impact and the ultimate goal of
      eliminating the disease. Through genomic epidemiology, we can appreciate
      bacterial population structure and its consequences for transmission dynamics,
      virulence, antimicrobial resistance, and development of new vaccines. Here, we
      review what we have learned through genomic epidemiological studies, following
      the rapid implementation of whole genome sequencing that can help to optimise
      preventative strategies for bacterial meningitis.

PMID- 29636910
TI  - Prospective surveillance of healthcare-associated infections and patterns of
      antimicrobial resistance of pathogens in an Italian intensive care unit.
AB  - Background: The study aimed to evaluate the distribution of healthcare-associated
      infections (HAIs), the incidence rates and device utilization ratio (DUR) of
      device-associated infections (DAIs), as well as the distribution and patterns of
      antimicrobial resistance of the responsible pathogens. Methods: Eligible patients
      who were admitted to an adult Intensive Care Unit (ICU) from May 1, 2013 to
      December 31, 2016 were included in the surveillance. Demographics, intrinsic and
      extrinsic risk factors, information regarding infection and isolated pathogens
      with antibiogram results were collected. Results: One thousand two hundred eighty
      three patients were included in the surveillance. One hundred forty-seven HAIs
      were detected with a cumulative incidence of 9.2 per 100 patients 4-year period
      and an incidence rate of 17.4 per 1000 patient days. Fifty-six out of 1283
      patients were affected by at least one episode of ICU-acquired pneumonia, and
      72.7% of these were associated with intubation. ICU-acquired bloodstream
      infections (BSIs) occurred in 4.4% of patients and 89.5% were catheter-related.
      ICU-acquired urinary tract infections (UTIs) occurred in 1% of patients, with
      84.6% of the episodes being associated with the use of an urinary catheter. The
      pattern of antimicrobial-resistance in the isolates showed, among the Gram
      positive bacteria, that 66.6% and 16.6% of Staphylococcus epidermidis were
      oxacillin and teicoplanin resistant, respectively. Among the Gram-negative
      bacteria, carbapenem resistance was found in 91.6% of Acinetobacter baumannii and
      28.5% of Klebsiella pneumoniae isolates. Conclusions: The majority of HAIs in the
      ICU studied were associated with the use of invasive devices. Since a significant
      proportion of these HAIs are considered preventable, reinforcement of the
      evidence-based preventive procedures are needed.

PMID- 29636911
TI  - Strain, disinfectant, concentration, and contact time quantitatively impact
      disinfectant efficacy.
AB  - Background: Transmission of healthcare-associated infections caused by antibiotic
      and multi-drug resistant (MDR) pathogens (e.g. Methicillin-resistant
      Staphylococcus aureus (MRSA), Pseudomonas aeruginosa) are a major concern in
      patient care facilities. Disinfectant usage is critical to control and prevent
      pathogen transmission, yet the relationships among strain, disinfectant type,
      contact time, and concentration are not well-characterized. We hypothesized that
      there would be significant differences in disinfectant efficacy among clinically
      relevant strains under off-label disinfectant conditions, but there would be less
      no differences among at registered label use concentrations and contact times.
      The purpose of this study was to quantify the effect of disinfectant
      concentration and contact time on the bactericidal efficacy of clinically
      relevant strains of S. aureus and P. aeruginosa. Methods: Accelerated hydrogen
      peroxide (AHP), quaternary ammonium compounds (Quat), and sodium hypochlorite
      were tested at label and reduced contact times and concentrations against four
      MDR P. aeruginosa strains and four MRSA strains. Quantitative EPA method MB-25-02
      was used to measure disinfectant efficacy reported as log10 reduction. Results:
      Both off-label disinfectant concentrations and contact times significantly
      affected efficacy of all disinfectants tested. Bactericidal efficacy varied among
      MRSA and P. aeruginosa strains. Conclusions: The quantitative disinfectant
      efficacy method used highlights the inter-strain variability that exists within a
      bacterial species. It also underscores the need for a disinfectant validation
      method that takes these variances into account.

PMID- 29636912
TI  - Bayesian Gaussian regression analysis of malnutrition for children under five
      years of age in Ethiopia, EMDHS 2014.
AB  - Background: The term malnutrition generally refers to both under-nutrition and
      over-nutrition, but this study uses the term to refer solely to a deficiency of
      nutrition. In Ethiopia, child malnutrition is one of the most serious public
      health problem and the highest in the world. The purpose of the present study was
      to identify the high risk factors of malnutrition and test different statistical
      models for childhood malnutrition and, thereafter weighing the preferable model
      through model comparison criteria. Methods: Bayesian Gaussian regression model
      was used to analyze the effect of selected socioeconomic, demographic, health and
      environmental covariates on malnutrition under five years old child's. Inference
      was made using Bayesian approach based on Markov Chain Monte Carlo (MCMC)
      simulation techniques in BayesX. Results: The study found that the variables such
      as sex of a child, preceding birth interval, age of the child, father's education
      level, source of water, mother's body mass index, head of household sex, mother's
      age at birth, wealth index, birth order, diarrhea, child's size at birth and
      duration of breast feeding showed significant effects on children's malnutrition
      in Ethiopia. The age of child, mother's age at birth and mother's body mass index
      could also be important factors with a non linear effect for the child's
      malnutrition in Ethiopia. Conclusions: Thus, the present study emphasizes a
      special care on variables such as sex of child, preceding birth interval,
      father's education level, source of water, sex of head of household, wealth
      index, birth order, diarrhea, child's size at birth, duration of breast feeding,
      age of child, mother's age at birth and mother's body mass index to combat
      childhood malnutrition in developing countries.

PMID- 29636913
TI  - Arachnoid diverticulum diagnosis following treatment of cryptococcal meningitis
      in a dog.
AB  - Successful long-term treatment of cryptococcal meningitis in dogs is clinically
      challenging. In humans, there are only rare case reports of complications post
      treatment including arachnoid diverticula. Combination antifungal therapy is
      standard of practice in human medicine and should be considered in veterinary
      patients.

PMID- 29636914
TI  - Combined mitral valve repair and heart transplantation.
AB  - In times of donor organ shortage, organs with extended allocation criteria, for
      example, valve pathologies, have to be taken into consideration for
      transplantation. The donor pool can be extended to hearts with mitral valve
      insufficiency. Mitral valve repair can rapidly be performed in the donor heart on
      the back table with excellent results.

PMID- 29636915
TI  - Multiple cerebral infarction revealing Takayasu's disease: a case report in a 32
      year-old man from Cameroon, sub-Saharan Africa.
AB  - This case suggests that young patients with few vascular risk factors, and who
      present with acute stroke syndrome involving more than one vascular territory
      should be screened for an inflammatory or infectious cause.

PMID- 29636916
TI  - Is shock impedance value alone to be considered a good predictor for shock
      efficacy in subcutaneous implantable cardioverter defibrillator?
AB  - Subcutaneous implantable cardioverter defibrillator (S-ICD) is easy to implant,
      with poor risks of the patient. However, fat is a poor current conductor and
      increases defibrillation threshold. As shock impedance alone should not be
      considered a good efficacy predictor of an S-ICD system, an X-ray latero-lateral
      view for lead position should be achieved.

PMID- 29636917
TI  - Solitary metastasis of ampullary carcinoma to the spleen: a case report.
AB  - Here, we report a first case of ampullary cancer with solitary metastasis of the
      spleen, which was successfully treated with pancreatoduodenectomy and splenectomy
      and was discharged 7 days after the operation with outpatient chemotherapy. In
      such cases, physicians should consider splenectomy as an effective treatment
      option.

PMID- 29636918
TI  - Patent Blue dye allergy and the deep inferior epigastric perforator free flap: a
      unique interaction.
AB  - Patent Blue dye for sentinel lymph node biopsy is associated with systemic
      allergic response and generalized blue hue. We report a unique case of successful
      free flap transfer in this setting. Despite inotropic support and abnormal blue
      hue, allergic response does not preclude safe flap transfer and monitoring.

PMID- 29636919
TI  - Attention deficit/hyperactivity disorder as an associated feature in OCTN2
      deficiency with novel deletion (p.T440-Y449).
AB  - This boy presented with ADHD at 3 years and at 8 years was hyperactive with no
      documented hypoglycemia and had myopathy, cardiomyopathy, and very low serum
      carnitine. L-carnitine improved his exercise intolerance, cardiomyopathy, and
      behavior. Analysis of SLC22A5 revealed a premature stop codon (p.R282*) and a
      novel in-frame deletion (p.T440-Y449).

PMID- 29636920
TI  - Prenatally diagnosed distal 16p11.2 microdeletion with a novel association with
      congenital diaphragmatic hernia: a case report.
AB  - A prenatal case presenting with congenital diaphragmatic hernia (CDH) and distal
      16p11.2 microdeletion suggests two possible causative hypotheses: (1) a
      functional effect of chromatin loopings between the distal and the proximal
      16p11.2 microdeletion traits, associated with CHD; (2) a possible role of ATP2A1,
      a deleted gene involved in diaphragm development.

PMID- 29636921
TI  - Not everything is as it seems: neurosarcoidosis presenting as leptomeningitis.
AB  - Involvement of the central nervous system in sarcoidosis is rare;
      neurosarcoidosis, although unusual, can present as leptomeningitis. The diagnosis
      is usually difficult because of the vague and broad symptomatology; therefore, a
      prompt diagnosis should be made, and adequate treatment should be administered to
      reduce morbidity and mortality.

PMID- 29636922
TI  - Hyperammonemic encephalopathy in a patient receiving fluorouracil/oxaliplatin
      chemotherapy.
AB  - Hyperammonemia is a rare adverse effect of 5-fluorouracil (5-FU) therapy, but can
      be very serious, even fatal. Physicians must be aware that hyperammonemic
      encephalopathy sometimes develops as an adverse event after 5-FU therapy.

PMID- 29636923
TI  - A case of immunoglobulin G4-related aortic diseases.
AB  - A 65-year-old man had histories of retroperitoneal fibrosis, membranous
      nephropathy, and acute coronary syndrome. Chest computed tomography showed an
      enlarged ascending aorta and type B aortic dissection, and he underwent ascending
      aorta and arch replacement. A pathological examination of the resected aorta
      showed immunoglobulin G4-positive plasma cell infiltration.

PMID- 29636924
TI  - A case of late orthostatic headache secondary to lumbar hidden dural fistula 20
      months after epidural anesthesia.
AB  - The clinical recognition of CSF fistula is a clinical challenge. We report the
      case of a young woman, who presented with a late orthostatic headache 20 months
      after epidural anesthesia. She developed a lumbar dural fistula of CSF confirmed
      in myelography CT scanning and treated successfully with epidural blood patch.

PMID- 29636925
TI  - A case report of chromosome 17q22-qter trisomy with distinct clinical
      presentation and review of the literature.
AB  - Terminal 17q trisomy is very rare but a recognizable genetic syndrome. The
      majority of cases reported are inherited from a balanced translocation carrier.
      This syndrome involves many organs and the severity ranges from mild to severe
      depending on the size of the 17q gain.

PMID- 29636926
TI  - Giant cell myocarditis causing refractory ventricular tachycardia in a pediatric
      patient.
AB  - Giant cell myocarditis should be considered in all pediatric patients with
      refractory ventricular arrhythmia. Endomyocardial biopsy should be obtained to
      confirm the diagnosis of giant cell myocarditis.

PMID- 29636927
TI  - Low-pitch peripheral systolic murmur associated with pulmonary embolism in the
      acute phase: a report of two cases.
AB  - Acute pulmonary embolism with significant right ventricular strain could be
      associated with a low-pitch peripheral systolic murmur radiating to the axillae.

PMID- 29636928
TI  - Bilateral bullous keratopathy secondary to melting keratitis in a Suri alpaca
      (Vicugna pacos).
AB  - An young alpaca was evaluated for bilateral progressive melting corneal ulcers
      and developped secondary bullous keratopathy during hospitalization. The tragic
      progression of melting ulcers in both eyes observed in our case leads us to
      recommend a rapid intensive medical therapy in young and debilitated alpacas
      presenting a corneal ulcer.

PMID- 29636929
TI  - PostOperative ST-segment elevation: not a blocked coronary artery, then what?
AB  - ST-segment elevation is well known for its diagnostic value for transmural
      myocardial infarction due to acute thrombotic occlusion of a coronary artery, and
      often requires emergency reperfusion therapy. However, ST segment is by no means
      pathognomonic for acute coronary events. Here, we report a case of ST-segment
      elevation after hepatectomy secondary to an unusual etiology.

PMID- 29636930
TI  - Frontline brentuximab vedotin in breast implant-associated anaplastic large-cell
      lymphoma.
AB  - We report a woman who developed BIA-ALCL 9 years after saline implant placement.
      The lymphoma manifested as a mass lesion associated with axillary
      lymphadenopathy. She was successfully treated with brentuximab vedotin with
      minimal toxicity. Brentuximab vedotin may be a promising frontline therapeutic
      modality for patients with BIA-ALCL.

PMID- 29636931
TI  - A superelderly case of TAFRO syndrome treated effectively using corticosteroid
      hormones.
AB  - Peripheral lymphocyte subsets may be less time-consuming and are a prognostic
      tool for managing thrombocytopenia, anasarca, myelofibrosis, renal dysfunction,
      and organomegaly (TAFRO) syndrome. Here, we report a superelderly case of plasma
      cell type TAFRO syndrome treated effectively using corticosteroid hormones.

PMID- 29636932
TI  - Successful treatment of refractory TAFRO syndrome with elevated vascular
      endothelial growth factor using thyroxine supplements.
AB  - Although the clinical significance of hypothyroidism in TAFRO syndrome is
      unknown, vascular endothelial growth factor (VEGF) levels decreased with
      improvements in the condition of our refractory TAFRO cases after thyroxine
      supplement therapy. Our results indicate that elevated VEGF levels are a
      potential factor in the pathogenesis and anasarca of TAFRO syndrome with
      hypothyroidism.

PMID- 29636933
TI  - Fever in a transplant recipient: think beyond infection.
AB  - Immune reconstitution inflammatory syndrome (IRIS) is an exaggerated inflammatory
      cascade initiated in response to immune recovery during the resolution of an
      infection. Reduction in calcineurin inhibitor levels in organ transplant
      recipients due to enhanced metabolism from interaction with rifampin can
      predispose these individuals to develop IRIS during the treatment of tuberculosis
      and mimic sepsis.

PMID- 29636934
TI  - Bladder squamous cell cancer accompanied by Trousseau's syndrome: a case report.
AB  - The association between thrombosis and cancer has been recognized since
      Trousseau's report in 1865. We present a case of bladder squamous cell carcinoma
      associated with multiple cerebral infarctions. This patient was diagnosed as
      having Trousseau's syndrome and received radiotherapy for bladder cancer
      treatment, along with anticoagulation therapy.

PMID- 29636935
TI  - Neonatal adrenal findings: significance and diagnostic approach. Description of
      two cases.
AB  - Abnormal adrenal findings such as hemorrhage or calcifications in the neonate can
      stem from a variety of etiologies. Clinical presentation can vary significantly
      based on the degree of hemorrhage or the associated condition. Thorough work-up
      is important to rule out critical underlying conditions as well as adrenal
      insufficiency.

PMID- 29636936
TI  - Human Appeasing Pheromone (HAP) influence on behavior and psychopathological
      residual symptoms of patients with complex psychiatric disorders.
AB  - This article is a case-report series showing the effectiveness of a three-month
      exposure to a synthetic analogue of Human Appeasing Pheromone as add-on strategy
      to psychopharmacological treatment on behavioral and residual symptoms of three
      patients suffering from severe psychiatric disorders with complex clinical
      pictures.

PMID- 29636937
TI  - Epiconus syndrome induced only in the erect standing position in a patient with
      L1 compression fracture: a representative case report.
AB  - In daily practice, when CT or MRI does not show a pathological lesion in a
      patient with persistent abnormal neurological signs, it is important to obtain
      imaging studies of the spine in dynamic position.

PMID- 29636938
TI  - Adult intussusceptions induced by a terminal ileum diverticulum: a case report.
AB  - We herein report a case of adult intussusceptions induced by a terminal ileum
      diverticulum. Histological examination confirmed a terminal ileum diverticulum
      full of feces, and it was considered an infiltrated region. The clinical
      characteristics of previously reported adult intussusceptions are also discussed,
      including jejunoileal diverticulum and surgical management.

PMID- 29636939
TI  - Malignant transformation of phyllodes tumor: a case report and review of
      literature.
AB  - Malignant phyllodes may transform from benign phyllodes; low-aggressive malignant
      phyllodes tumor is manageable by locally wide excision.

PMID- 29636940
TI  - A point mutation in Phe71Ser in glycoprotein IX as a genetic cause of Bernard
      Soulier syndrome: case report.
AB  - We need to be aware of rare causes of persistent thrombocytopenia as Bernard
      Soulier syndrome (BSS). When BSS is suspected based on family history and giant
      platelets, genetic test for mutations of GPIbIXV is necessary. Management varies
      once you recognize the cause. Platelets transfusion and antifibrinolytics are the
      mainstay of therapy.

PMID- 29636941
TI  - Unusual presentation of oral pyogenic granulomas: a review of two cases.
AB  - Pyogenic granuloma is a benign vascular neoplasm of the oral cavity that usually
      presents as a small nodular lesion, the gingiva being the commonest site.
      Occasionally it occurs at uncommon sites with unusual sizes. Here we describe two
      cases of oral pyogenic granulomas that had an unusual presentation.

PMID- 29636942
TI  - A vascular anomaly of the iliac artery in a patient with VATER association.
AB  - In patients with VATER association, some have vascular anomaly that makes
      procedure difficult. Pretreatment CT angiography should be necessary for the
      patients with VATER association's feature.

PMID- 29636943
TI  - Systemic thrombolysis and endovascular thrombectomy in severe acute ischemic
      stroke after dabigatran reversal with idarucizumab.
AB  - Patients presenting with an acute ischemic stroke despite dabigatran therapy
      (last intake <24 h or unknown) should be evaluated for reversal by idarucizumab,
      making them eligible for safe and effective intravenous thrombolysis. It has been
      shown to be feasible, well-tolerated, and easy to manage in an emergency room or
      stroke unit.

PMID- 29636944
TI  - Successful management of extremely high-output refractory congenital chylothorax
      with chemical pleurodesis using 4% povidone-iodine and propranolol: a case
      report.
AB  - First-line therapy for congenital chylothorax is conservative treatment. However,
      surgical intervention or chemical pleurodesis is required for refractory cases.
      With all the concerns regarding its complications, povidone-iodin provided a
      successful management for a high-output congenital chylothorax. However, renal
      and thyroid function must be monitored during treatment.

PMID- 29636945
TI  - Pacemaker implantation in a challenging anatomy: isolated persistent left
      superior vena cava and azygos continuation of interrupted inferior vena cava.
AB  - Isolated persistent left superior vena cava (SVC) in the absence of right SVC is
      a rare congenital variant of thoracic venous drainage with the left subclavian
      and jugular veins that drain into the right atrium through the coronary sinus.
      Inferior vena cava interruption with azygos continuation is another congenital
      anomaly resulting in venous drainage of the lower extremities via a typically
      dilated azygos vein. Although both variants are generally asymptomatic and
      incidentally detected, these can have clinical implications in specific
      circumstances and in particular during device implantation. We report a case of
      pacemaker implantation in which both anatomical variants were present.

PMID- 29636946
TI  - A case of patient with renal lupus with an initial presentation of hemolytic
      uremic syndrome triggered by streptococcal infection.
AB  - Systemic lupus erythematosus (SLE) is a systemic disease that is presented in a
      myriad of ways. Renal involvement is common in SLE and usually presents
      clinically as glomerulonephritis. We describe patients with SLE presented
      initially with hemolytic uremic syndrome which is a distinctive initial
      presentation.

PMID- 29636947
TI  - Diagnostic challenges in a patient with an occult insulinoma:68 Ga-DOTA-exendin-4
      PET/CT and 68Ga-DOTATATE PET/CT.
AB  - Despite growing evidence for GLP-1R molecular-based imaging, successful
      localization of insulinomas may require the use of multiple imaging modalities.
      Not all benign insulinomas express the GLP-1R as expected. Our case demonstrates
      that there is a still an important role for traditional methods for the
      anatomical localization of an insulinoma.

PMID- 29636948
TI  - Durable treatment response of relapsing CNS plasmacytoma using intrathecal
      chemotherapy, radiotherapy, and Daratumumab.
AB  - CNS myelomatous involvement is a rare complication of multiple myeloma with
      dismal outcome. This disease's optimal treatment is unclear. Combined approach of
      systemic therapy, radiotherapy, and intrathecal injections chemotherapy should be
      considered and autologous stem cell transplant consolidation is offered to
      eligible patients. The role of Daratumumab in this disease deserves further
      evaluation.

PMID- 29636949
TI  - Bilaterally enlarged adrenal glands without obvious cause: need for a
      multidisciplinary diagnostic work-up.
AB  - Bilateral enlarged adrenal glands are rare, and as diagnostic delay may have
      serious consequences for the patient, we recommend a multidisciplinary approach
      of specialists in the field of endocrinology, oncology, radiology, and clinical
      chemistry prior to the start of the diagnostic work-up.

PMID- 29636950
TI  - Observational study of laryngoscopy plus flow-volume loops during exercise.
AB  - Laryngoscopy is the gold standard to diagnose exercise-induced laryngeal
      obstruction, though inspiratory flow-volume loop may provide a clue. We combined
      tidal flow-volume loop analysis plus laryngoscopy during exercise and found that
      cigar-shaped - not flattened - inspiratory loops are associated with obstruction.
      Pursed-lip breathing slows inhalation thereby reducing vocal fold adduction.

PMID- 29636951
TI  - Detection of Taenia saginata infection mimicking Crohn's disease using video
      capsule endoscopy.
AB  - Capsule endoscopy was used to detect intestinal Taenia saginata infection in a 19
      year-old man. The patient was initially believed to have Crohn's disease due to a
      notable family history of the disease. Capsule endoscopy is a valuable tool for
      diagnosing tapeworm infection even when Crohn's disease is suspected.

PMID- 29636952
TI  - Invasive tracheobronchial aspergillosis developed during radioimmunotherapy for
      malignant lymphoma.
AB  - Invasive pulmonary aspergillosis (IPA) often occurs during the treatment of
      malignant lymphoma. However, invasive tracheobronchial aspergillosis (ITBA) is a
      rare form of IPA. Particularly, due to the decrease in immunity associated with
      chemotherapy, it is difficult to diagnose ITBA only by CT imaging and serological
      findings. Pathologic diagnosis by bronchoscopy is important.

PMID- 29636953
TI  - Angioimmunoblastic T-cell lymphoma: a rare subtype of peripheral T-cell lymphoma.
AB  - Angioimmunoblastic T-cell lymphoma (AITL) is a rare form of NHL and usually
      presents in the late stage due to the atypical laboratory findings.
      Immunohistochemistry of the lymph node in AITL is characterized by positive CD2,
      CD3, CD4, CD10, CXCL-13, PD1 often BCL-6 and CD20 positive. Meshworks of
      follicular dendritic cells are seen outside follicles with CD21 and CD23 stains.
      EBV can be often positive as well. Autologous transplantation should be offered
      in the first remission as poor outcome is reported with anthracycline-containing
      regimens.

PMID- 29636954
TI  - Simultaneous finding of chronic lymphocytic leukemia and residual hairy cell
      leukemia using a lymphocyte-binding anti-CD antibody microarray.
AB  - The morphologic diagnosis of hairy cell leukemia coexisting with another
      lymphoproliferative disorder is hindered by the small size of hairy cell
      population. It can be simplified by presorting peripheral blood mononuclear cell
      using an anti-CD antibody microarray on transparent support (including anti
      CD11c, CD25, CD103, and CD123) before their morphology analysis.

PMID- 29636955
TI  - Intrasinusoidal pattern of bone marrow infiltration by hepatosplenic T-cell
      lymphoma.
AB  - Hepatosplenic T-cell lymphoma is a rare, aggressive form of extranodal lymphoma,
      which frequently involves the bone marrow. An intrasinusoidal pattern of
      infiltration is characteristic of the disease and is often best appreciated on
      immunohistochemical staining. Bone marrow biopsy can be a useful diagnostic tool.

PMID- 29636956
TI  - Coccidioides immitis soft tissue infection mimicking pseudofolliculitis barbae.
AB  - Endemic fungal infections can present atypically and should be considered in the
      differential diagnosis of any soft tissue infection not responding appropriately
      to antibiotic therapy. Diagnosis can be confirmed with a biopsy. Most fungal soft
      tissue infections require extended duration of treatment.

PMID- 29636957
TI  - Parapelvic cysts mimicking hydronephrosis.
AB  - Point-of-care renal ultrasonography performed by physicians at bedside assists in
      rapid evaluation of hydronephrosis, nephrolithiasis and other structural
      abnormalities, and guides management. As such, it is important to differentiate
      between various renal pathologies that can mimic one another and herein, we
      present a case where parapelvic cysts mimicked hydronephrosis.

PMID- 29636958
TI  - Renal cyst infection: a diagnostic dilemma.
AB  - Cyst infection is a common complication of autosomal dominant polycystic kidney
      disease. It presents with vague clinical features and imaging findings which make
      the diagnosis challenging. Imaging findings can be misinterpreted as renal cell
      carcinoma, and biopsy of the lesion is often required for definitive diagnosis.

PMID- 29636959
TI  - Pneumothorax secondary to pulmonary alveolar microlithiasis.
AB  - Pulmonary alveolar microlithiasis (PAM) is a rare impairment of pulmonary
      phosphate clearance that leads to gradual precipitation of intra-alveolar calcium
      phosphate microliths. There is often a striking difference between alarming
      clinical imaging and a relatively well patient. Pneumothorax in PAM often only
      respond to surgical intervention.

PMID- 29636960
TI  - Massive pericardial effusion caused by hypothyroidism.
AB  - Although mild pericardial effusion is a usual finding in patients with
      hypothyroidism, massive pericardial effusion or pericardial tamponade is rare and
      customarily related to severe hypothyroidism. The diagnosis of hypothyroidism
      should be considered in the differential of patients presenting with unexplained
      pericardial effusion, even when signs and symptoms of hypothyroidism are
      nonexistent.

PMID- 29636961
TI  - Subarachnoid hemorrhage secondary to cerebral venous sinus thrombosis.
AB  - Subarachnoid hemorrhage as a presentation of cerebral venous sinus thrombosis
      (CVST) is a rare but recognized phenomenon. A high index of suspicion among
      clinicians and an awareness of subtle CT features can avoid delayed diagnosis of
      underlying CVST [Eur J Neurol., 17, 2010, 1249]. Prompt but careful
      anticoagulation can prevent significant associated morbidity and mortality.

PMID- 29636963
TI  - Milk fistula following puerperal breast abscess.
AB  - We present the first reported video of milk fistula. Milk fistula is a rare
      complication secondary to abscess or breast intervention in lactating women. It
      is a clinical diagnosis and the treatment is usually conservative, which included
      cessation of breastfeeding, with a good prognosis.

PMID- 29636962
TI  - Blastic plasmacytoid dendritic cell neoplasm.
AB  - Blastic plasmacytoid dendritic cell neoplasm is an aggressive neoplasm with a
      median survival of only a few months despite treatment. An exhaustive
      immunohistochemical workup is required to differentiate it from myeloid sarcoma
      and extranodal NK/T cell lymphoma. Treatment is with induction using a regimen
      utilized for leukemia. Allogeneic hematopoietic stem cell transplantation is
      recommended for those who achieve remission following induction.

PMID- 29636964
TI  - Quantifying and reducing statistical uncertainty in sample-based health program
      costing studies in low- and middle-income countries.
AB  - Objectives: In many low- and middle-income countries, the costs of delivering
      public health programs such as for HIV/AIDS, nutrition, and immunization are not
      routinely tracked. A number of recent studies have sought to estimate program
      costs on the basis of detailed information collected on a subsample of
      facilities. While unbiased estimates can be obtained via accurate measurement and
      appropriate analyses, they are subject to statistical uncertainty. Quantification
      of this uncertainty, for example, via standard errors and/or 95% confidence
      intervals, provides important contextual information for decision-makers and for
      the design of future costing studies. While other forms of uncertainty, such as
      that due to model misspecification, are considered and can be investigated
      through sensitivity analyses, statistical uncertainty is often not reported in
      studies estimating the total program costs. This may be due to a lack of
      awareness/understanding of (1) the technical details regarding uncertainty
      estimation and (2) the availability of software with which to calculate
      uncertainty for estimators resulting from complex surveys. We provide an overview
      of statistical uncertainty in the context of complex costing surveys, emphasizing
      the various potential specific sources that contribute to overall uncertainty.
      Methods: We describe how analysts can compute measures of uncertainty, either via
      appropriately derived formulae or through resampling techniques such as the
      bootstrap. We also provide an overview of calibration as a means of using
      additional auxiliary information that is readily available for the entire
      program, such as the total number of doses administered, to decrease uncertainty
      and thereby improve decision-making and the planning of future studies. Results:
      A recent study of the national program for routine immunization in Honduras shows
      that uncertainty can be reduced by using information available prior to the
      study. This method can not only be used when estimating the total cost of
      delivering established health programs but also to decrease uncertainty when the
      interest lies in assessing the incremental effect of an intervention. Conclusion:
      Measures of statistical uncertainty associated with survey-based estimates of
      program costs, such as standard errors and 95% confidence intervals, provide
      important contextual information for health policy decision-making and key inputs
      for the design of future costing studies. Such measures are often not reported,
      possibly because of technical challenges associated with their calculation and a
      lack of awareness of appropriate software. Modern statistical analysis methods
      for survey data, such as calibration, provide a means to exploit additional
      information that is readily available but was not used in the design of the study
      to significantly improve the estimation of total cost through the reduction of
      statistical uncertainty.

PMID- 29636965
TI  - "What Cannot be Missed": a New Service of Arrhythmia and Electrophysiology
      Review.

PMID- 29636966
TI  - Unmissable Papers, 2017.

PMID- 29636967
TI  - Non-invasive Cardiac Radiation for Ablation of Ventricular Tachycardia: a New
      Therapeutic Paradigm in Electrophysiology.
AB  - Non-invasive ablation of cardiac tissue to control ventricular tachycardia (VT)
      is a novel therapeutic consideration in the management of ventricular arrhythmias
      associated with structural heart disease. The technique involves the use of
      stereotactic radiotherapy delivered to VT substrates. Although invasive mapping
      can be used to identify the target, the use of non-invasive ECG and imaging
      techniques combined with multi-electrode body-surface ECG recordings offers the
      potential of a completely non-invasive approach. Early case series have
      demonstrated a consistent decrease in VT burden and sufficient early safety to
      allow more detailed multicenter studies. Such studies are currently in progress
      to further evaluate this promising technology.

PMID- 29636968
TI  - How to Prevent, Detect and Manage Complications Caused by Cryoballoon Ablation of
      Atrial Fibrillation.
AB  - Atrial fibrillation is the most common cardiac arrhythmia and the prevalence is
      increasing every year. Patients who fail to maintain sinus rhythm with use of
      anti-arrhythmic drug therapy are referred for catheter ablation. Cryoballoon (CB)
      ablation has emerged as an effective and alternative treatment option to
      traditional point-by-point radiofrequency ablation, but there can be
      complications. This article reviews the incidence, presentation, risk factors,
      management and preventative strategies of three major complications associated
      with CB ablation: phrenic nerve injury, atrial oesophageal fistula and bronchial
      injury. Although these complications are rare, electrophysiologists should
      institute measures to identify high-risk patients, implement best-practice
      techniques to minimise risks and maintain a high index of suspicion to recognise
      the complications quickly and implement correct treatment strategies.

PMID- 29636969
TI  - Oesophageal Injury During AF Ablation: Techniques for Prevention.
AB  - Atrial fibrillation remains the most common arrhythmia worldwide, with pulmonary
      vein isolation (PVI) being an essential component in the treatment of this
      arrhythmia. In view of the close proximity of the oesophagus with the posterior
      wall of the left atrium, oesophageal injury prevention has become a major concern
      during PVI procedures. Oesophageal changes varying from erythema to fistulas have
      been reported, with atrio-oesophageal fistulas being the most feared as they are
      associated with major morbidity and mortality. This review article provides a
      detailed description of the risk factors associated with oesophageal injury
      during ablation, along with an overview of the currently available techniques to
      prevent oesophageal injury. We expect that this state of the art review will
      deliver the tools to help electrophysiologists prevent potential oesophageal
      injuries, as well as increase the focus on research areas in which evidence is
      lacking.

PMID- 29636971
TI  - Systematic Screening for Atrial Fibrillation in the Community: Evidence and
      Obstacles.
AB  - With an ageing population globally, the burden of atrial fibrillation (AF) and
      its consequent complication of stroke and risk of mortality will continue to
      increase. Although opportunistic screening for AF by pulse check or ECG rhythm
      strip for people >65 years of age is currently recommended, data are now emerging
      that demonstrate the possible benefits of systematic community screening. Such
      screening is capable of identifying previously undiagnosed AF in 0.5-3.0 % of all
      those screened. The effectiveness of screening programmes will be markedly
      weakened by the lack of a structured downstream management pathway, making it a
      mandatory component in any AF screening programme for the general population.
      Different tools, especially smartphone-based devices, have made AF screening in
      the community more feasible. However, the sensitivities and positive predictive
      values of the current versions of automated diagnostic algorithms for AF have to
      be improved further to increase the cost-efficiency of screening programmes.

PMID- 29636970
TI  - Asymptomatic Ventricular Pre-excitation: Between Sudden Cardiac Death and
      Catheter Ablation.
AB  - Debate about the best clinical approach to the management of asymptomatic
      patients with ventricular pre-excitation and advice on whether or not to
      invasively stratify and ablate is on-going. Weak evidence about the real risk of
      sudden cardiac death and the potential benefit of catheter ablation has probably
      prevented the clarification of action in this not infrequent and sometimes
      conflicting clinical situation. After analysing all available data, real evidence
      based medicine could be the alternative strategy for managing this group of
      patients. According to recent surveys, most electrophysiologists invasively
      stratify. Based on all accepted risk factors - younger age, male, associated
      structural heart disease, posteroseptal localisation, ability of the accessory
      pathway to conduct anterogradely at short intervals of <=250 milliseconds and
      inducibility of sustained atrioventricular re-entrant tachycardia and/or atrial
      fibrillation - a shared decisionmaking process on catheter ablation is proposed.

PMID- 29636972
TI  - Atrial Arrhythmias in Pulmonary Hypertension: Pathogenesis, Prognosis and
      Management.
AB  - Atrial arrhythmias, including atrial fibrillation and atrial flutter, are common
      in patients with pulmonary hypertension and are closely associated with clinical
      decompensation and poor clinical outcomes. The mechanisms of arrhythmogenesis and
      subsequent clinical decompensation are reviewed. Practical implications and
      current evidence for the management of atrial arrhythmias in patients with
      pulmonary hypertension are summarised.

PMID- 29636973
TI  - Drivers of Atrial Fibrillation: Theoretical Considerations and Practical
      Concerns.
AB  - Understanding the mechanisms responsible for driving AF is key to improving the
      procedural success for AF ablation. In this review, we look at some of the
      proposed drivers of AF, the disagreement between experts and the challenges
      confronted in attempting to map AF. Defining a 'driver' is also controversial,
      but for the purposes of this review we will consider an AF driver to be either a
      focal or localised source demonstrating fast, repetitive activity that propagates
      outward from this source, breaking down in to disorganisation further away from
      its origin.

PMID- 29636975
TI  - Unravelling the Mysteries of the Human AV Node.

PMID- 29636974
TI  - The Significance of Drug-Drug and Drug-Food Interactions of Oral Anticoagulation.
AB  - Vitamin K antagonists (VKAs) such as warfarin are the most commonly prescribed
      oral anticoagulants worldwide. However, factors affecting the pharmacokinetics of
      VKAs, such as food and drugs, can cause deviations from their narrow therapeutic
      window, increasing the bleeding or thrombosis risk and complicating their long
      term use. The use of direct oral anticoagulants (DOACs) offers a safer and more
      convenient alternative to VKAs. However, it is important to be aware that plasma
      levels of DOACs are affected by drugs that alter the cell efflux transporter P
      glycoprotein and/or cytochrome P450. In addition to these pharmacokinetic-based
      interactions, DOACs have the potential for pharmacodynamic interaction with
      antiplatelet agents and non-steroidal anti-inflammatory drugs. This is an
      important consideration in patient groups already at high risk of bleeding, such
      as patients with renal impairment.

PMID- 29636976
TI  - Hybrid Approach for Atrial Fibrillation Ablation: the Jury is Still Out.

PMID- 29636978
TI  - Maternal iron status during pregnancy and respiratory and atopic outcomes in the
      offspring: a Mendelian randomisation study.
AB  - Introduction: Limited evidence from birth cohort studies suggests that lower
      prenatal iron status may be a risk factor for childhood respiratory and atopic
      outcomes, but these observational findings may be confounded. Mendelian
      randomisation (MR) can potentially provide unconfounded estimates of causal
      effects by using common genetic variants as instrumental variables. We aimed to
      study the relationship between prenatal iron status and respiratory and atopic
      outcomes in the offspring using MR. Methods: In the Avon Longitudinal Study of
      Parents and Children birth cohort, we constructed four maternal genotypic risk
      scores by summing the total number of risk alleles (associated with lower iron
      status) across single nucleotide polymorphisms known to be associated with at
      least one of four iron biomarkers (serum iron, ferritin, transferrin and
      transferrin saturation). We used MR to study their associations with respiratory
      and atopic outcomes in children aged 7-9 years (n=6002). Results: When analyses
      were restricted to mothers without iron supplementation during late pregnancy,
      negative associations were found between the maternal transferrin saturation
      score and childhood forced expiratory volume in 1 s and forced vital capacity
      (difference in age, height and gender-adjusted SD units per SD increase in
      genotypic score: -0.05 (-0.09, -0.01) p=0.03, and -0.04 (-0.08, 0.00) p=0.04,
      respectively). Conclusion: Using MR we have found weak evidence suggesting that
      low maternal iron status during pregnancy may cause impaired childhood lung
      function.

PMID- 29636977
TI  - Electrical dynamics of isolated cerebral and skeletal muscle endothelial tubes:
      Differential roles of G-protein-coupled receptors and K+ channels.
AB  - Electrical dynamics of freshly isolated cerebral endothelium have not been
      determined independently of perivascular nerves and smooth muscle. We tested the
      hypothesis that endothelium of cerebral and skeletal muscle arteries
      differentially utilizes purinergic and muscarinic signaling pathways to activate
      endothelium-derived hyperpolarization. Changes in membrane potential (Vm) were
      recorded in intact endothelial tubes freshly isolated from posterior cerebral and
      superior epigastric arteries of male and female C57BL/6 mice (age: 3-8 months).
      Vm was measured in response to activation of purinergic (P2Y) and muscarinic (M3)
      receptors in addition to small- and intermediate-conductance Ca2+-activated K+
      (SKCa/IKCa) and inward rectifying K+ (KIR) channels using ATP (100 MUmol.L-1),
      acetylcholine (ACh; 10 MUmol.L-1), NS309 (0.01-10 MUmol.L-1), and 15 mmol.L-1
      KCl, respectively. Intercellular coupling was demonstrated via transfer of
      propidium iodide dye and electrical current (+/-0.5-3 nA) through gap junctions.
      With similarities observed across gender, peak hyperpolarization to ATP and ACh
      in skeletal muscle endothelial tubes was ~twofold and ~sevenfold higher,
      respectively, vs cerebral endothelial tubes, whereas responses to NS309 were
      similar (from resting Vm ~-30 mV to maximum ~-80 mV). Hyperpolarization (~8 mV)
      occurred during 15 mmol.L-1 KCl treatment in cerebral but not skeletal muscle
      endothelial tubes. Despite weaker hyperpolarization during endothelial GPCR
      stimulation in cerebral vs skeletal muscle endothelium, the capability for robust
      SKCa/IKCa activity is preserved across brain and skeletal muscle. As vascular
      reactivity decreases with aging and cardiovascular disease, endothelial K+
      channel activity may be calibrated to restore blood flow to respective organs
      regardless of gender.

PMID- 29636979
TI  - British Thoracic Society Quality Standards for acute non-invasive ventilation in
      adults.
AB  - Introduction: The purpose of the quality standards document is to provide
      healthcare professionals, commissioners, service providers and patients with a
      guide to standards of care that should be met for the provision of acute non
      invasive ventilation in adults together with measurable markers of good practice.
      Methods: Development of British Thoracic Society (BTS) Quality Standards follows
      the BTS process of quality standard production based on the National Institute
      for Health and Care Excellence process manual for the development of quality
      standards. Results: 6 quality statements have been developed, each describing a
      standard of care for the provision of acute non-invasive ventilation in the UK,
      together with measurable markers of good practice. Conclusion: BTS Quality
      Standards for acute non-invasive ventilation in adults form a key part of the
      range of supporting materials that the Society produces to assist in the
      dissemination and implementation of guideline's recommendations.

PMID- 29636980
TI  - Posttransplant Lymphoproliferative Disorder in Adults Receiving Kidney
      Transplantation in British Columbia: A Retrospective Cohort Analysis.
AB  - Background: Posttransplant lymphoproliferative disorder (PTLD) is a major
      complication following kidney transplantation. Objective: We undertook this study
      to characterize PTLD in kidney transplant patients in British Columbia with
      regard to incidence, patient and graft survival, histological subtypes, treatment
      modalities, and management of immunosuppression. Design: Retrospective cohort
      analysis. Setting: British Columbia. Patients: All adult patients who underwent
      kidney transplantation in British Columbia between January 1, 1996, and December
      31, 2012, were included. Patients less than 18 years of age at the time of first
      transplant and multiple organ transplant recipients were excluded from analysis.
      Measurements: Patients with lymphoproliferative disorders that occurred
      subsequent to kidney transplantation were considered to have developed PTLD.
      Methods: Cases of PTLD were identified by cross-referencing data abstracted from
      the provincial transplant agency's clinical database with the provincial cancer
      agency's lymphoma registry. Patients were followed up for the development of PTLD
      until December 31, 2012, and for outcomes of death and graft failure until
      December 31, 2014. Data collection was completed via an electronic chart review.
      Results: Of 2217 kidney transplant recipients, 37 (1.7%) developed PTLD. Nine
      cases were early-onset PTLD, occurring within 1 year of transplant; of these
      cases, 6 were known/presumed Epstein-Barr virus mismatch, compared with only 2 of
      28 late-onset cases. Patient survival for early-onset PTLD was 100% at 2 years
      post diagnosis. Late-onset PTLD had survival rates of 71.4% and 67.9% at 1 and 2
      years, respectively. PTLD was associated with significantly decreased patient
      survival (P = .031) and graft survival (uncensored for death, P = .017), with
      median graft survival of PTLD and non-PTLD patients being 9.5 and 16 years,
      respectively. Immunosuppressant therapy was reduced in the majority of patients;
      additional therapies included rituximab monotherapy, CHOP-R, radiation, and
      surgery. Limitations: Limitations to this study include its retrospective nature
      and the unknown adherence of patients to prescribed immunosuppressant regimens.
      In addition, cumulative doses of immunosuppression received and the degree of
      immunosuppression reduction for PTLD management were not effectively captured.
      Conclusions: The incidence of PTLD in British Columbia following kidney
      transplantation was low and consistent with rates reported in the literature. The
      incidence of late-onset PTLD and its association with reduced patient and graft
      survival warrant further analysis of patients' long-term immunosuppression.

PMID- 29636981
TI  - Perceived Benefits and Challenges of a Risk-Based Approach to Multidisciplinary
      Chronic Kidney Disease Care: A Qualitative Descriptive Study.
AB  - Background: The kidney failure risk equation (KFRE) provides an estimate of risk
      of progression to kidney failure, and may guide clinical care. Objective: We
      aimed to describe patient, family, and health care provider's perspectives of the
      perceived benefits and challenges of using a risk-based approach to guide care
      delivery for patients with advanced chronic kidney disease (CKD), and refine
      implementation based on their input. Methods: We used qualitative methodology to
      explore perceived benefits and challenges of implementing a risk-based approach
      (using the KFRE) to determine eligibility for multidisciplinary CKD care in
      Southern Alberta. We obtained perspectives from patients and families through
      focus groups, as well as input from health care providers through interviews and
      open-ended responses from an online survey. Twelve patients/family members
      participated in 2 focus groups, 16 health care providers participated in an
      interview, and 40 health care providers responded to the survey. Results:
      Overall, participants felt that a KFRE-based approach had the potential to
      improve efficiency of the clinics by targeting care to patients at highest risk
      of kidney failure; however, they also expressed concerns about the impact of loss
      of services for lower risk individuals. Participants also articulated concerns
      about a perceived lack of capacity for adequate CKD patient care in the
      community. Our implementation strategy was modified as a result of participants'
      feedback. Conclusions: We identified benefits and challenges to implementation of
      a risk-based approach to guide care of patients with advanced CKD. Based on these
      results, our implementation strategy has been modified by removing the category
      of referral back to primary care alone, and instead having that decision made
      jointly by nephrologists and patients among low-risk patients.

PMID- 29636982
TI  - Crossing barriers: a multidisciplinary approach to children and adults with young
      onset movement disorders.
AB  - Background: Diagnosis of less common young-onset movement disorders is often
      challenging, requiring a broad spectrum of skills of clinicians regarding
      phenotyping, normal and abnormal development and the wide range of possible
      acquired and genetic etiologies. This complexity often leads to considerable
      diagnostic delays, paralleled by uncertainty for patients and their families.
      Therefore, we hypothesized that these patients might benefit from a
      multidisciplinary approach. We report on the first 100 young-onset movement
      disorders patients who visited our multidisciplinary outpatient clinic. Methods:
      Clinical data were obtained from the medical records of patients with disease
      onset before age 18 years. We investigated whether the multidisciplinary team,
      consisting of a movement disorder specialist, pediatric neurologist, pediatrician
      for inborn errors of metabolism and clinical geneticist, revised the movement
      disorder classification, etiological diagnosis, and/or treatment. Results: The
      100 referred patients (56 males) had a mean age of 12.5 +/- 6.3 years and mean
      disease duration of 9.2 +/- 6.3 years. Movement disorder classification was
      revised in 58/100 patients. Particularly dystonia and myoclonus were recognized
      frequently and supported by neurophysiological testing in 24/29 patients.
      Etiological diagnoses were made in 24/71 (34%) formerly undiagnosed patients,
      predominantly in the genetic domain. Treatment strategy was adjusted in 60
      patients, of whom 43 (72%) reported a subjective positive effect. Conclusions:
      This exploratory study demonstrates that a dedicated tertiary multidisciplinary
      approach to complex young-onset movement disorders may facilitate phenotyping and
      improve recognition of rare disorders, with a high diagnostic yield and minimal
      diagnostic delay. Future studies are needed to investigate the cost-benefit ratio
      of a multidisciplinary approach in comparison to regular subspecialty care.

PMID- 29636984
TI  - Thiazide diuretic-caused hyponatremia in the elderly hypertensive: will a bottle
      of Nepro a day keep hyponatremia and the doctor away? Study protocol for a proof
      of-concept feasibility trial.
AB  - Background: Hypertension is the most common modifiable risk factor for
      cardiovascular disease, with an increasing prevalence with age, but with easily
      available medications to control it. Adverse effects of these medications do
      limit their use, in particular hyponatremia due to thiazide and thiazide-like
      diuretics. This is more common in the elderly patients due to a combination of
      inadequate protein intake and impaired urinary dilution capability, made worse by
      additional thiazide use. Limiting free water intake and increasing protein intake
      are often not successful resulting in thiazide avoidance. Daily protein
      supplement is a potential option in this clinical scenario. We describe the
      protocol for a feasibility study to explore this option. Methods: This is a
      single-arm, prospective, open-label proof-of-concept trial, including elderly
      patients with thiazide diuretic-induced hyponatremia. Forty patients will be
      enrolled and receive a bottle of a protein supplement daily, providing 120 mmol
      of solutes and permitting an extra 163 mL free water loss, for 4 weeks. The main
      outcome measures will be (1) feasibility for enrollment, (2) safety of the
      intervention, and (3) potential efficacy of the intervention in improving
      hyponatremia. Secondary outcome measures will include changes in urine
      osmolality, body weight, and urea measurements. Discussion: Thiazide diuretic
      induced hyponatremia is an important adverse effect, with significant clinical
      impact, such as delirium and falls, and limits the use of these potent
      antihypertensive agents. There are little data on the effect or safety of protein
      supplementation and also on whether a trial of this is feasible. The results of
      this proof-of-concept feasibility trial will help plan and execute a larger
      definitive trial to test protein supplementation as an effective strategy in this
      condition. Trial registration: The trial is registered with Clinical trials,
      registration identifier: NCT02614807.

PMID- 29636983
TI  - A 6-week hip muscle strengthening and lumbopelvic-hip core stabilization program
      to improve pain, function, and quality of life in persons with patellofemoral
      osteoarthritis: a feasibility pilot study.
AB  - Background: Patellofemoral joint (PFJ) osteoarthritis (OA) is prevalent in middle
      aged and older adults. Despite this, there are minimal studies which have
      examined conservative interventions for PFJ OA. Weakness of proximal lower
      extremity muscles is associated with PFJ OA. It is unknown if a hip muscle
      strengthening and lumbopelvic-hip core stabilization program will improve
      symptoms and function in persons with PFJ OA. This study examined the feasibility
      and impact of a 6-week hip muscle strengthening and core stabilization program on
      pain, symptoms, physical performance, peak muscle torques, and quality of life in
      persons with PFJ OA. Methods: Ten females with PFJ OA and ten age- and sex
      matched controls participated in baseline tests. PFJ OA participants attended ten
      twice-a-week hip strengthening and core stabilization exercise sessions. Outcome
      measures included questionnaires, the Timed-Up-and-Go, and peak isometric torque
      of hip and quadriceps muscles. Data were tested for normality; parametric and non
      parametric tests were used as appropriate. Results: At baseline, the PFJ OA group
      had significantly worse symptoms, slower Timed-Up-and-Go performance, and lower
      muscle torques than control participants. PFJ OA group adherence to supervised
      exercise sessions was adequate. All PFJ OA participants attended at least nine
      exercise sessions. Five PFJ OA participants returned 6-month follow-up
      questionnaires, which was considered fair retention. The PFJ OA participants'
      self-reported pain, symptoms, function in daily living, function in sport, and
      quality of life all improved at 6 weeks (P < 0.05). Timed-Up-and-Go time score
      improved at 6 weeks (P = 0.005). Peak hip external rotator torque increased (P =
      0.01). Improvements in pain and self-reported function were no longer significant
      6 months following completion of the intervention. Conclusions: PFJ OA
      participants were adherent to the supervised sessions of the intervention.
      Improvement in symptoms, physical performance, and muscle torque were found after
      6 weeks. Participant retention at 6 months was fair, and significant changes were
      no longer present. Our findings suggest that a hip strengthening and core
      stabilization program may be beneficial to improve symptoms, function, and
      physical performance in persons with PFJ OA. Future studies are needed, and
      additional measures should be taken to improve long-term adherence to exercise.
      Trial registration: ClinicalTrials.gov NCT02825238. Registered 6 July 2016
      (retrospectively registered).

PMID- 29636986
TI  - Differences in self-reported weekend catch up sleep between children and
      adolescents with and without primary hypertension.
AB  - Background: The data on the association of sleep duration and blood pressure in
      the pediatric age group have been mixed and most studies have focused on weekday
      sleep duration. The purpose of this study was to compare the weekday and weekend
      sleep patterns between children and adolescents with newly diagnosed primary
      hypertension and a normotensive control group. Methods: Children and adolescents
      from a pediatric nephrology clinic, aged 6-18 years with newly diagnosed primary
      hypertension were compared to an age and sex matched normotensive control group
      from a general pediatric clinic. The questions about bed time and getting out of
      bed times from the Pediatric Sleep Questionnaire (PSQ) were used to obtain
      weekday and weekend bed time, getting out of bed time and sleep duration. The
      Pediatric Daytime Sleepiness Scale (PDSS) was used to assess subjective
      sleepiness. Results: In both groups of 60 subjects each, weekday total sleep time
      was similar. Subjects in both groups went to bed later and woke up later on the
      weekends. However, in the hypertensive group, weekend getting out of the bed time
      was earlier (8:52 AM +/-93 min vs. 9:36 AM +/-88 min, p = 0.013) and weekend
      catchup sleep was about 40 min less (62.8 +/- 85.5 vs. 102.7 +/- 84.9, p =
      0.035). Hypertensive children perceived less subjective sleepiness (PDSS scores
      8.28 +/- 4.88 vs. 10.63 +/- 5.41, p = 0.007). The p values were calculated after
      adjusting for body mass index (BMI), race, daytime nap, caffeine use, sleep
      related breathing disorder (SRBD) scale and periodic limb movement of sleep
      (PLMS) scale subcomponents of the PSQ. Conclusions: Hypertensive children
      obtained less weekend catch up sleep and reported less subjective sleepiness
      compared to the control group. More weekend sleep may potentially mitigate the
      effect of weekday sleep deprivation on blood pressure.

PMID- 29636985
TI  - Recent trends in bioinks for 3D printing.
AB  - Background: The worldwide demand for the organ replacement or tissue regeneration
      is increasing steadily. The advancements in tissue engineering and regenerative
      medicine have made it possible to regenerate such damaged organs or tissues into
      functional organ or tissue with the help of 3D bioprinting. The main component of
      the 3D bioprinting is the bioink, which is crucial for the development of
      functional organs or tissue structures. The bioinks used in 3D printing
      technology require so many properties which are vital and need to be considered
      during the selection. Combination of different methods and enhancements in
      properties are required to develop more successful bioinks for the 3D printing of
      organs or tissue structures. Main body: This review consists of the recent state
      of-art of polymer-based bioinks used in 3D printing for applications in tissue
      engineering and regenerative medicine. The subsection projects the basic
      requirements for the selection of successful bioinks for 3D printing and
      developing 3D tissues or organ structures using combinations of bioinks such as
      cells, biomedical polymers and biosignals. Different bioink materials and their
      properties related to the biocompatibility, printability, mechanical properties,
      which are recently reported for 3D printing are discussed in detail. Conclusion:
      Many bioinks formulations have been reported from cell-biomaterials based bioinks
      to cell-based bioinks such as cell aggregates and tissue spheroids for tissue
      engineering and regenerative medicine applications. Interestingly, more tunable
      bioinks, which are biocompatible for live cells, printable and mechanically
      stable after printing are emerging with the help of functional polymeric
      biomaterials, their modifications and blending of cells and hydrogels. These
      approaches show the immense potential of these bioinks to produce more complex
      tissue/organ structures using 3D bioprinting in the future.

PMID- 29636987
TI  - Consensus on management of metastatic colorectal cancer in Central America and
      the Caribbean: San Jose, Costa Rica, August 2016.
AB  - Colorectal cancer (CRC) is the third most common cancer in men and the second
      most common in women worldwide. In Latin America and the Caribbean, it has a
      mortality of 56%. The median overall survival for patients with metastatic
      colorectal cancer (mCRC) is currently estimated as ~30 months, which has
      substantially improved through strategic changes in treatment and in the
      management of patients. As opposed to other metastatic cancers where first-line
      regimens are often determined, mCRC requires special attention because there is
      controversy in the possible combinations of the available drugs and the different
      periods of duration for each patient. Each combination must seek to be effective
      and to generate the minimum adverse effects as possible. Instead of giving the
      first-line regimen until the tumour progresses, treatment is often
      individualised. Furthermore, up to 60% of colorectal tumours are considered non
      mutated or wild-type CRC. Not harbouring mutations in the RAS family of genes or
      mutations in the signalling pathways of the epidermal growth factor receptor
      causes a null response to anti-epidermal growth factor receptor antibody therapy,
      which implies even more complex considerations regarding its management. The
      primary objective of this consensus is to address the main scenarios of mCRC in
      order to warrant the most appropriate therapeutic intervention for these patients
      in the Central American and the Caribbean (CAC) region. This can lead to better
      clinical outcomes as well as quality of life for palliative patients. This
      document includes the formal expert consensus recommendations for scenarios of
      mutated and non-mutated mCRC, including synchronous or metachronous disease,
      management of mCRC with liver and lung metastasis, resectable, potentially
      resectable or non-resectable tumours and local in the CAC context.

PMID- 29636988
TI  - Four distinct immune microenvironment subtypes in gastric adenocarcinoma with
      special reference to microsatellite instability.
AB  - Introduction: Programmed death-ligand 1 (PD-L1) can be overexpressed in tumours
      other than Epstein-Barr virus (EBV)-positive (EBV+) or microsatellite instability
      high (MSI-H) gastric cancer (GC) subtypes. We aimed to determine the tumour
      immune microenvironment (TME) classification of GC to better understand tumour
      immune interactions and help patient selection for future immunotherapy with
      special reference to MSI-H. Methods: Immunohistochemistry (IHC) for PD-L1 and
      CD8+ T cells in three distinct subtypes of GC (43 EBV+, 79 MSI-H and 125 EBV
      /MSS) were performed and analysed. In 66 MSI-H GC, mutation counts were compared
      with PD-L1 expression and survival of the patients. Results: GC TME divided by PD
      L1 IHC and tumour-infiltrating lymphocytes (TIL) measured by intratumoural CD8
      density showed: (1) about 40% of GC are type I (PD-L1+/TIL+) consisting ~70% of
      MSI-H or EBV+ GC, and ~15% of EBV-/microsatellite stable (MSS) GC patients show
      the best survival in both disease-free (HR 2.044) and overall survival (HR
      1.993); this type would respond to a checkpoint blockade therapy; (2) almost 30%
      of GC are type II (PD-L1-/TIL-) with the worst survival; (3) approximately 10% of
      GC are type III (PD-L1+/TIL-); and (4) up to 20% are type IV (PD-L1-/TIL+) and,
      unexpectedly, ~25% of EBV+ or MSI-H GC are within this subtype. In MSI-H GC,
      frequent frameshift mutations were observed in ARID1A, RNF43, NF1, MSH6, BRD3,
      NCOA3, BCORL1, TNKS2 and NPM1 and the numbers of frameshift mutation correlated
      significantly with PD-L1 expression (P<0.05). Discussion: GC can be classified
      into four TME types based on PD-L1 and TIL, and numbers of frameshift mutation
      correlate well with PD-L1 expression in MSI-H GC.

PMID- 29636990
TI  - Recent advances in adjuvant therapy for patients with melanoma.

PMID- 29636989
TI  - Comprehensive molecular screening by next generation sequencing reveals a
      distinctive mutational profile of KIT/PDGFRA genes and novel genomic alterations:
      results from a 20-year cohort of patients with GIST from north-western Greece.
AB  - Introduction: Gastrointestinal stromal tumours (GIST) are mesenchymal neoplasms
      that usually carry an activating mutation in KIT or platelet-derived growth
      factor receptor alpha (PDGFRA) genes with predictive and prognostic significance.
      We investigated the extended mutational status of GIST in a patient population of
      north-western Greece in order to look at geopraphic/genotypic distinctive traits.
      Patient and methods: Clinicopathological and molecular data of 38 patients
      diagnosed from 1996 to 2016 with GIST in the region of Epirus in Greece were
      retrospectively assessed. Formalin-fixed paraffin-embedded tumours were
      successfully analysed for mutations in 54 genes with oncogenic potential. Next
      generation sequencing was conducted by using the Ion AmpliSeqCancer Hotspot Panel
      V.2 for DNA analysis (Thermofisher Scientific). Results: Among 38 tumours, 24
      (63.16%) and seven (18.42%) of the tumours harboured mutations in the KIT and
      PDGFRA genes, respectively, while seven (18.42%) tumours were negative for either
      KIT or PDGFRA mutation. No mutations were detected in five (13.16%) cases.
      Concomitant mutations of BRAF and fibroblast growth factor receptor 3 (FGFR3)
      genes were observed in two patients with KIT gene mutation. Two patients with
      KIT/PDGFRA wild-type GIST had mutations in either KRAS or phosphatidylinositol
      4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) genes. There was no
      significant survival difference regarding the exonic site of mutation in either
      KIT or PDGFRA gene. The presence of a mutation in pathway effectors downstream of
      KIT or PDGFRA, such as BRAF, KRAS or PIK3CA, was associated with poor prognosis.
      Adverse prognosticators were also high mitotic index and the advanced disease
      status at diagnosis. Conclusions: We report comparable incidence of KIT and
      PDGFRA mutation in patients with GIST from north-western Greece as compared with
      cohorts from other regions. Interestingly, we identified rare mutations on RAS,
      BRAF and PIK3CA genes in patients with poor prognosis.

PMID- 29636992
TI  - Controversies in oncology: which adjuvant endocrine therapy is to be given to
      premenopausal patients with hormone receptor-positive breast cancer?

PMID- 29636991
TI  - Relevance of a molecular tumour board (MTB) for patients' enrolment in clinical
      trials: experience of the Institut Curie.
AB  - Background: High throughput molecular screening techniques allow the
      identification of multiple molecular alterations, some of which are actionable
      and can be targeted by molecularly targeted agents (MTA). We aimed at evaluating
      the relevance of using this approach in the frame of Institut Curie Molecular
      Tumor Board (MTB) to guide patients with cancer to clinical trials with MTAs.
      Patients and methods: We included all patients presented at Institut Curie MTB
      from 4 October 2014 to 31 October 2017. The following information was extracted
      from the chart: decision to perform tumour profiling, types of molecular
      analyses, samples used, molecular alterations identified and those which are
      actionable, and inclusion in a clinical trial with matched MTA. Results: 736
      patients were presented at the MTB. Molecular analyses were performed in 442
      patients (60%). Techniques used included next-generation sequencing, comparative
      genomic hybridisation array and/or other techniques including
      immunohistochemistry in 78%, 51% and 58% of patients, respectively. Analyses were
      performed on a fresh frozen biopsy in 91 patients (21%), on archival tissue
      (fixed or frozen) in 326 patients (74%) and on both archival and fresh frozen
      biopsy in 25 patients (6%). At least one molecular alteration was identified in
      280 analysed patients (63%). An actionable molecular alteration was identified in
      207 analysed patients (47%). Forty-five analysed patients (10%) were enrolled in
      a clinical trial with matched MTA and 29 additional patients were oriented and
      included in a clinical trial based on a molecular alteration identified prior to
      the MTB analysis. Median time between date of specimen reception and molecular
      results was 28 days (range: 5-168). Conclusions: The implementation of an MTB at
      Institut Curie enabled the inclusion of 10% of patients into a clinical trial
      with matched therapy.

PMID- 29636994
TI  - Targeting autophagy in chemotherapy-resistant of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a malignant tumor with poor prognosis. Surgical
      resection is recommended for very early-stage and early-stage HCC, but HCC is
      still prone to recurrence and metastasis after surgery. Furthermore, treatment
      options for intermediate- and advanced-stage HCC are relatively limited. Systemic
      therapy is the preferred method to kill residual cancer cells after surgery and
      prolong survival time of inoperable patients, but most cases are insensitive to
      chemotherapeutic agents, restricting widespread clinical application of systemic
      therapy. Many studies have found that various chemotherapeutic drugs for HCC
      treatment can increase autophagic flux of HCC cells, and it may be related with
      enhancing drug resistance and promoting cell survival. However, enhancement of
      autophagic flux may also induce tumor cell death in some cases, leading to marked
      inconsistency across studies. Here we reviewed the mechanisms underlying the
      increase in autophagic flux in HCC cells induced by chemotherapeutic drugs and
      examined the contributions of autophagy and related pathways to chemotherapy drug
      resistance. Our aim was to identify potential autophagy-related targets for
      improving the sensitivity of HCC to chemotherapeutic drugs.

PMID- 29636995
TI  - Anticancer efficacies of arsenic disulfide through apoptosis induction, cell
      cycle arrest, and pro-survival signal inhibition in human breast cancer cells.
AB  - Arsenic disulfide, a major effective component of realgar, has been investigated
      for its anti-cancer potential and shown to have therapeutic efficacies in
      hematological and some solid tumors. However, its effect against breast cancer is
      rarely reported. In this study, we investigated the anti-cancer effects of As2S2
      in human breast cancer cell lines MCF-7 and MDA-MB-231, and further elucidated
      its underlying mechanisms. As2S2 significantly inhibited cell viabilities,
      induced apoptosis, and led to cell cycle arrest in both cell lines with a dose-
      and time-dependent manner. As2S2 upregulated pro-apoptotic proteins like p53 and
      PARP in MCF-7 cells. Besides, As2S2 downregulated anti-apoptotic proteins like
      Bcl-2 and Mcl-1, as well as cell cycle-related proteins cyclin A2 and cyclin D1
      in both cell lines. Of note, the expression level of cyclin B1 was downregulated
      in MCF-7 cells, whereas, upregulated in MDA-MB-231 cells. Moreover, As2S2
      significantly inhibited the pro-survival signals in PI3K/Akt pathway in both cell
      lines. In conclusion, As2S2 inhibited cell viabilities, induced apoptosis and
      cell cycle arrest in both MCF-7 and MDA-MB-231 cell lines by regulating the
      expression of key proteins involved in related pathways. These results provide
      fundamental insights into the clinical application of As2S2 for treatment of
      patients with breast cancer.

PMID- 29636993
TI  - Circulating biomarkers for early diagnosis of pancreatic cancer: facts and hopes.
AB  - Pancreatic cancer (PC) is characterized by extremely high mortality and poor
      prognosis, which are largely ascribed to difficulties in early diagnosis and
      limited therapeutics. Although there is a sufficient window for intervention
      before preneoplastic lesions progress to invasive disease, effective early
      detection of PC remains difficult using current biomarkers and imaging
      techniques. Biomarkers with satisfactory diagnostic efficacy and convenient
      analysis methods are urgently required. In this review, we summarized recent
      advances in the identification of biomarkers in circulation for early detection
      of PC. A number of novel circulating biomarkers, such as metabolites, cell-free
      DNA (cfDNA), noncoding RNA, and exosomes, that show promising diagnostic value
      have been discovered using advances in sequencing techniques and "omics"
      analyses. Panels comprising several biomarkers may also exhibit better diagnostic
      performance. In the future, we need more efficient circulating biomarkers for the
      identification of noninvasive precursor lesions and early disease. Collaborative
      large-scale studies are also required to show the clinical validity and
      applicability of potential biomarkers.

PMID- 29636996
TI  - BCL7B, a predictor of poor prognosis of pancreatic cancers, promotes cell
      motility and invasion by influencing CREB signaling.
AB  - The functions of B-cell CLL/lymphoma 7B (BCL7B) are unknown and the protein lacks
      any known functional domains. The aim of this study was to investigate the role
      of BCL7B in the motility and invasiveness of pancreatic cancer cells.
      Immunohistochemistry was performed to determine whether high BCL7B expression in
      human pancreatic cancer tissues is correlated with poor prognosis. High BCL7B
      expression was an independent predictor of worse overall survival of pancreatic
      cancer patients. Immunocytochemistry showed that BCL7B was accumulated in cell
      protrusions of migrating pancreatic cancer cells. Knockdown of BCL7B inhibited
      the motility and invasiveness of pancreatic cancer cells through a decrease in
      cell protrusions. Phosphoprotein array analysis was performed to determine BCL7B
      associated intracellular signaling pathways. Suppression of BCL7B increased
      phosphorylated CREB expression in pancreatic cancer cells, and knockdown of CREB
      promoted the motility and invasiveness by increasing cell protrusions. The
      combined data suggest that BCL7B promotes pancreatic cancer cell motility and
      invasion through a signaling pathway that involves dephosphorylation of CREB.

PMID- 29636997
TI  - MicroRNA-337 regulates the PI3K/AKT and Wnt/beta-catenin signaling pathways to
      inhibit hepatocellular carcinoma progression by targeting high-mobility group AT
      hook 2.
AB  - MicroRNAs (miRNAs) serve as major regulators during the tumorigenesis and tumor
      development of hepatocellular carcinoma (HCC). In addition, miRNAs may serve as
      new promising biomarkers for the diagnosis and prognosis and as effective
      therapeutic targets for patients with this malignancy. Therefore, understanding
      the association between miRNAs and HCC may be beneficial to discover novel
      therapeutic approaches towards diagnosis and treatments. Results of this study
      showed that miRNA-337 (miR-337) was markedly downregulated in HCC tissues and
      cell lines. Decreased miR-337 expression was significantly associated with the
      TNM stage and lymph node metastasis of HCC. Ectopic expression of miR-337
      prohibited the proliferation, colony formation, migration, and invasion of HCC
      cells. It also promoted the apoptosis in vitro and reduced the tumor growth in
      vivo of these cells. High-mobility group AT-hook 2 (HMGA2) was identified as a
      direct target gene of miR-337 in HCC through a series of experiments. HMGA2 was
      significantly overexpressed in HCC tissues and negatively correlated with miR-337
      expression. Moreover, the functions of HMGA2 inhibition were similar to those
      induced by miR-337 in HCC. Restored HMGA2 expression rescued the tumor
      suppressive roles of miR-337 overexpression in HCC. Furthermore, miR-337
      overexpression inhibited the activation of PI3K/AKT and Wnt/beta-catenin
      signaling pathways in HCC both in vitro and in vivo. This study demonstrated that
      miR-337 may play tumor-suppressing roles in HCC, at least partly, via directly
      targeting HMGA2 and inhibiting the PI3K/AKT and Wnt/beta-catenin signaling
      pathways. Therefore, miR-337 may be a novel and effective target for the
      therapeutic treatment of patients with HCC.

PMID- 29636998
TI  - EZH2 promotes migration and invasion of triple-negative breast cancer cells via
      regulating TIMP2-MMP-2/-9 pathway.
AB  - Triple-negative breast cancer (TNBC) has a higher potential for invasion and
      metastasis than other types of breast cancer. Enhancer of zeste homolog 2 (EZH2)
      is the catalytic core protein in the polycomb repressive complex 2 (PRC2), which
      catalyzes the trimethylation of histone H3 at lysine 27 (H3K27me3) and mediates
      gene silencing of the target genes that are involved in fundamental cellular
      processes, such as the cell fate decision, cell cycle regulation, senescence,
      cell differentiation, and cancer formation. A consistent association between TNBC
      metastasis and EZH2 has not been confirmed. The aim of this study was to
      investigate the role of EZH2 in the regulation of tissue inhibitor of
      metalloproteinase (TIMPs) and matrix metalloproteinases (MMPs) to promote
      metastasis of TNBC cells and to characterize the metastasis-associated genes
      regulated by EZH2 in TNBC cells. We found that high levels of EZH2 expression
      induce repression of TIMP2 transcription, leading to increased activity of MMP-2
      and MMP-9 and thus to increased invasive activity of TNBC cells.

PMID- 29637000
TI  - Expression profiles analysis identifies a novel three-mRNA signature to predict
      overall survival in oral squamous cell carcinoma.
AB  - Oral squamous cell carcinoma (OSCC) remains to be a challenging public health
      problem worldwide. However, the underlying molecular mechanism regulating the
      carcinogenesis of OSCC is poorly known. Gene expression profiles of GSE13601,
      GSE30784, GSE37991 and The Cancer Genome Atlas (TCGA) head and neck cancer were
      downloaded from gene expression omnibus (GEO) and TCGA database respectively. R
      software and bioconductor packages were used to compare and identify the
      differentially expressed genes (DEGs) between OSCC tissues and normal controls.
      The common DEGs were then subjected to gene ontology (GO) enrichment analysis,
      ingenuity pathway analysis (IPA), protein-protein interaction (PPI) network
      analysis as well as survival analysis. A total of 76 up- and 102 down-regulated
      DEGs were identified. Functional analysis revealed that these DEGs were
      associates with increased oncostatin M signaling, cell diapedesis and
      extravasation as well as reduced calcium signaling and loss of adherens junctions
      and tight junctions. A set of robust prognostic signatures including PLAU, CLDN8
      and CDKN2A were identified from DEGs and could predict overall survival in OSCC
      patients from TCGA cohort. This three-gene signature was further successfully
      validated as a prognostic marker for overall survival prediction in another
      independent cohort GSE41613. In conclusion, our study has identified a registry
      of novel genes and pathways that play important roles in regulating the
      initiation and development of OSCC. A set of robust molecular signature is
      identified for prognostic prediction, which will provide useful guidance for
      therapeutic applications.

PMID- 29636999
TI  - microRNA-532 suppresses the PI3K/Akt signaling pathway to inhibit colorectal
      cancer progression by directly targeting IGF-1R.
AB  - Substantial evidence has shown that numerous microRNAs (miRNAs) are deregulated
      in colorectal cancer (CRC) and that their dysregulation is involved in CRC
      formation and progression. miRNA-based targeted therapy that inhibits or restores
      expression may be a promising therapeutic approach for anti-cancer therapy.
      Therefore, a comprehensive investigation of the mechanisms underlying CRC
      occurrence and development may help identify effective therapeutic targets for
      the therapy of CRC, thus improving the prognosis of patients with this disease.
      This study showed that miRNA-532 (miR-532) was significantly down-regulated in
      CRC tissues and cell lines. Low miR-532 expression strongly correlated with
      aggressive clinicopathological characteristics, including tumor size, lymphatic
      metastasis and TNM stage. Exogenous expression of miR-532 restricted cell
      proliferation, colony formation, migration and invasion; promoted cell apoptosis
      in vitro; and reduced tumor growth in vivo. Mechanistically, insulin-like growth
      factor 1 receptor (IGF-1R) was determined to be a novel direct target gene of miR
      532 in CRC. In clinical CRC tissues, the expression of miR-532 was inversely
      correlated with that of IGF-1R, which was clearly overexpressed in CRC tissues.
      Furthermore, IGF-1R silencing simulated the tumor-suppressing roles of miR-532 in
      CRC. Moreover, recovered IGF-1R expression antagonized the inhibitory effects of
      miR-532 overexpression on CRC cells. Notably, miR-532 overexpression inhibited
      activation of the PI3K/Akt signaling pathway in CRC, both in vitro and in vivo.
      These results indicate that miR-532 plays an important role in CRC development,
      partly by directly targeting IGF-1R and regulating the PI3K/Akt signaling
      pathway. Thus, the miR-532/IGF-1R axis has clinical significance in the therapy
      of patients with CRC.

PMID- 29637001
TI  - Highly expressed histone deacetylase 5 promotes the growth of hepatocellular
      carcinoma cells by inhibiting the TAp63-maspin pathway.
AB  - Aberrant expression of histone deacetylases (HDACs) has been detected in a
      variety of cancers, which disrupts the balance between cell proliferation and
      apoptosis in favor of continuous growth. A previous study demonstrated that HDAC5
      contributes to the proliferation of hepatocellular carcinoma (HCC) cells, but a
      clear understanding of the mechanism has not yet been provided. In the present
      work, we found that the levels of HDAC5 were significantly higher in HCC tissues
      and cells than in adjacent tissues and normal hepatic cells. In addition,
      knockdown of HDAC5 attenuated the proliferation of Hep3B and HepG2 cells. Through
      profiling the expressions of proliferation and apoptosis-related genes in Hep3B
      cells following HDAC5 knockdown, p63 and maspin were found obviously up-regulated
      in HDAC5-deprived cells compared with the control. Further investigations
      confirmed that HDAC5 knockdown induced TAp63 expression in HCC cells, accompanied
      with increased H3K9 acetylation at the TAp63 promoter. Overexpression of TAp63
      led to proliferation inhibition by inducing cell cycle arrest. Additionally,
      TAp63 that was required for the maspin upregulation resulted from HDAC5
      knockdown. Phenotype experiments showed that interrupting either TAp63 or maspin
      recovered the proliferative and tumorigenic capabilities of HCC cells with HDAC5
      knockdown. Clinical analysis showed that HDAC5 was negatively correlated with
      TAp63 and maspin in HCC tissues. In addition, a high level of HDAC5 as well as a
      low level of TAp63 or maspin predicted poor survival in HCC patients. Taken
      together, this study proposes the existence of an aberrant HDAC5-TAp63-maspin
      pathway conferring HCC progression through proliferation induction, which
      suggests novel intervention targets for the disease.

PMID- 29637002
TI  - MiR-216a exerts tumor-suppressing functions in renal cell carcinoma by targeting
      TLR4.
AB  - MiR-216a, a tumor-related microRNA (miRNA), has been reported to be implicated in
      the tumorigenesis and progression of diverse types of human malignancies;
      however, its role in renal cell carcinoma (RCC) remains unclear. This study aimed
      to explore the biological role of miR-216a in RCC and clarify the potential
      mechanisms involved. In the present study, miR-216a was found to be significantly
      down-regulated in both RCC tissues and cell lines. Functional studies
      demonstrated that enhanced expression of miR-216a suppressed RCC cell
      proliferation, migration and invasion in vitro, inhibited tumor growth in vivo,
      and induced RCC cell cycle arrest and apoptosis. Moreover, the tumor-suppressing
      effects of miR-216a in RCC were abrogated by the miR-216a inhibitor treatment.
      Notably, toll-like receptor 4 (TLR4) was downregulated by miR-216a via direct
      binding to its 3' untranslated region in RCC cells. Furthermore, TLR4 expression
      was discovered to be markedly up-regulated and inversely correlated with miR-216a
      expression in RCC tissues. Mechanistic studies revealed that restoring the
      expression of TLR-4 alleviated miR-216a-induced inhibitory effects on
      proliferation, migration and invasion of RCC cells. Taken together, these
      findings suggest that miR-216a functions as a tumor suppressor in RCC by directly
      targeting TLR4 and that miR-216a might be a novel therapeutic target for RCC.

PMID- 29637003
TI  - TGF-beta1 expression in regulatory NK1.1-CD4+NKG2D+ T cells dependents on the
      PI3K-p85alpha/JNK, NF-kappaB and STAT3 pathways.
AB  - NK1.1-CD4+NKG2D+ cells exert their immune-regulatory function in tumor as an
      unconventional regulatory T cell subset through the production of TGF-beta1;
      however, the molecular mechanisms involving with the activation of nuclear
      factors for TGF-beta1 transcription remain unclear. Here we determined that the
      PI3K-p85alpha subunit was specifically activated in NK1.1-CD4+NKG2D+ cells
      following an 8-hour stimulation by sRAE-1 or alpha-CD3/sRAE-1, subsequently
      leading to the activation of PI3K-p110, Akt, and JNK. On the contrary, alpha
      CD3/alpha-CD28 stimulation did not induce the activation of PI3K-p85 and JNK.
      Consequently, activation of the nuclear transcription factor AP-1 as a
      consequence of JNK activation regulated TGF-beta1 expression in NK1.1-CD4+NKG2D+
      cells. Furthermore, activation of NF-kappaB in NK1.1-CD4+NKG2D+ cells resulted
      from both protein kinase C activation downstream of TCR/CD3 signaling and PI3K
      activation induced by NKG2D engagement. The STAT3-Y705 phosphorylation, as
      activated by PI3K, under stimulations of the sRAE-1 or alpha-CD3/sRAE-1 also
      contributed to the TGF-beta1 expression in NK1.1-CD4+NKG2D+ cells. Moreover, ChIP
      assay confirmed that STAT3 was capable of binding with the promoter regions of
      TGF-beta1. In conclusion, our data showed that the TGF-beta1 transcription in
      NK1.1-CD4+NKG2D+ cells induced by sRAE-1 or alpha-CD3/sRAE-1 was involved with
      the AP-1, NF-kappaB, and STAT3 signaling pathways; therefore, regulation of AP-1,
      NF-kappaB, and STAT3 activation may play important roles in the development and
      function of NK1.1-CD4+NKG2D+ cells.

PMID- 29637004
TI  - Cholangiocarcinoma: molecular imaging-guided radiofrequency hyperthermia-enhanced
      intratumoral herpes simplex virus thymidine kinase gene therapy.
AB  - We investigated the feasibility of using radiofrequency hyperthermia (RFH) to
      enhance green fluorescent protein (GFP)/herpes simplex virus thymidine kinase
      (HSV-TK)/ganciclovir (GCV) gene therapy of cholangiocarcinoma. Cholangiocarcinoma
      cells and mice with cholangiocarcinoma were treated by (i) GFP/HSV-TK/plasmid
      combined with RFH at 42 degrees C, followed by ganciclovir administration; (ii)
      HSV-TK alone; (iii) RFH alone; and (iv) saline. The therapeutic effects among
      different treatments were evaluated by bioluminescent optical imaging and
      ultrasound imaging. For the technical validation, GFP/HSV-TK/plasmid was
      intrabiliarily injected into pig common bile duct (CBD) walls using a needle
      integrated balloon catheter with or without RFH enhancement. GFP gene expression
      was evaluated by optical imaging, which was correlated with histology. The
      results show that combination therapy of HSV-TK plus RFH significantly induced
      lower cell viabilities and decreased bioluminescence signals compared the other
      three groups, which were further confirmed by the tumor volume decrease with
      combination therapy, as measured by ultrasound imaging. Optical imaging of CBD
      tissues demonstrated an increased GFP expression in the group with RFH
      enhancement, compared that with non-RFH treatment. We concluded that intratumoral
      RFH can enhance the therapeutic effect of GFP/HSV-TK/plasmid on
      cholangiocarcinoma, which may open new avenues for effective treatment of this
      deadly disease.

PMID- 29637005
TI  - YY1 and HDAC9c transcriptionally regulate p38-mediated mesenchymal stem cell
      differentiation into osteoblasts.
AB  - Mesenchymal stem cells (MSCs) have a high self-renewal potential and can
      differentiate into various types of cells, including adipocytes, osteoblasts, and
      chondrocytes. Previously, we reported that the enhancer of zeste homolog 2
      (EZH2), the catalytic component of the Polycomb-repressive complex 2, and HDAC9c
      mediate the osteogenesis and adipogenesis of MSCs. In the current study, we
      identify the role of p38 in osteogenic differentiation from a MAPK antibody array
      screen and investigate the mechanisms underlying its transcriptional regulation.
      Our data show that YY1, a ubiquitously expressed transcription factor, and HDAC9c
      coordinate p38 transcriptional activity to promote its expression to facilitate
      the osteogenic potential of MSCs. Our results show that p38 mediates osteogenic
      differentiation, and this has significant implications in bone-related diseases,
      bone tissue engineering, and regenerative medicine.

PMID- 29637006
TI  - Energy stress-induced lncRNA HAND2-AS1 represses HIF1alpha-mediated energy
      metabolism and inhibits osteosarcoma progression.
AB  - During recent years, long noncoding RNAs (lncRNAs) have been recognized as key
      regulators in the development and progression of human cancers, however, their
      roles in osteosarcoma metabolism are still not well understood. The present study
      aims to investigate the expression profiles and potential modulation of specific
      lncRNA(s) in osteosarcoma metabolism. The high-throughput Hiseq sequencing was
      performed to screen for abnormally expressed lncRNAs in osteosarcoma cells
      cultured under glucose starvation condition, and lncRNA HAND2-AS1 was eventually
      identified as one that was significantly up-regulated when compared with normal
      cultured cells. Mechanistic investigations indicated that knockdown of HAND2-AS1
      abrogated the energy stress-induced effect on cell apoptosis and proliferation,
      and promoted osteosarcoma progression. Moreover, knockdown of HAND2-AS1 promoted
      glucose uptake, lactate production, and the expression level of a serious of
      enzymes that involved in energy metabolism. Subsequently, RNA pull-down and RNA
      immuneprecipitation revealed that, upon energy stress, HAND2-AS1 regulated
      osteosarcoma metabolism through sequestering FBP1 from binding to HIF1alpha,
      thereby releasing HIF1alpha expression and promoting the protein level. Taken
      together, our integrated approach reveals a regulatory mechanism by lncRNA HAND2
      AS1 to control energy metabolism and tumor development in osteosarcoma. Thus,
      HAND2-AS1 may be a potential biomarker and therapeutic target for the repression
      of osteosarcoma metabolism.

PMID- 29637007
TI  - A feedback loop consisting of RUNX2/LncRNA-PVT1/miR-455 is involved in the
      progression of colorectal cancer.
AB  - Long non-coding RNAs (lncRNAs) have been shown to participate in cancer
      progression. In the present study, we explored the potential roles of lncRNA-PVT1
      in the development process of colorectal cancer (CRC) via miR-455. We found that
      PVT1 is up-regulated in human CRC tissues compared to adjacent normal tissues. A
      functional study showed that the silencing of PVT1 expression by siRNAs inhibited
      cell proliferation, migration and invasion, whereas the overexpression of PVT1
      accelerated cell proliferation, migration and invasion in vitro. A mechanistic
      study indicated PVT1 regulated the growth of CRC tumors by acting as a competing
      endogenous RNAs (ceRNA) and negatively regulated miR-455. Furthermore, we
      discovered that RUNX2, a functional transcription factor in CRC, up-regulated
      PVT1 expression. Therefore, our study suggested that the RUNX2/PVT1/miR-455
      regulatory axis plays an important role in CRC tumorigenesis and may be a
      therapeutic target for the treatment of CRC.

PMID- 29637008
TI  - Overexpression of golgi membrane protein 1 promotes non-small-cell carcinoma
      aggressiveness by regulating the matrix metallopeptidase 13.
AB  - Non-small-cell carcinoma (NSCLC) is one of the most lethal malignancies of lung
      cancers and its prognosis remains dismal due to the paucity of effective
      therapeutic targets. Recent reports show that Golgi membrane protein 1 (GOLM1) is
      highly expressed in a variety of tumor cells, functions as a negative regulator
      of T cells and then promotes tumor progression. However, its expression and role
      in NSCLC remain unclear. Herein, we showed that GOLM1 was markedly up-regulated
      in NSCLC cell lines and clinical tissues. Clinically, NSCLC patients with high
      expression of GOLM1 had shorter overall survival (OS) and high GOLM1 expression
      in tumor samples was significantly related to malignant phenotype, such as lymph
      node metastasis and high tumor stage. Ectopic expression of GOLM1 in NSCLC cells
      induced epithelial-to-mesenchymal transition (EMT) and promoted proliferation,
      migration, and invasion of NSCLC cells in vitro. Furthermore, GOLM1
      overexpressing significantly promoted the tumorigenicity of NSCLC cells in vivo
      whereas silencing endogenous GOLM1 caused an opposite outcome. Moreover, we
      demonstrated that GOLM1 enhanced NSCLC aggressiveness by activating matrix
      metalloproteinase-13 (MMP13) signaling. Together, our results provided new
      evidence that GOLM1 overexpression promoted the progression of NSCLC and might
      represent a novel therapeutic target for its treatment.

PMID- 29637009
TI  - Epidemiology of the Zika Virus Outbreak in the Cabo Verde Islands, West Africa.
AB  - Introduction: The Zika virus (ZIKV) outbreak in the island nation of Cabo Verde
      was of unprecedented magnitude in Africa and the first to be associated with
      microcephaly in the continent. Methods: Using a simple mathematical framework we
      present a first epidemiological assessment of attack and observation rates from
      7,580 ZIKV notified cases and 18 microcephaly reports between July 2015 and May
      2016. Results: In line with observations from the Americas and elsewhere, the
      single-wave Cabo Verdean ZIKV epidemic was characterized by a basic reproductive
      number of 1.85 (95% CI, 1.5 - 2.2), with overall the attack rate of 51.1% (range
      42.1 - 61.1) and observation rate of 2.7% (range 2.29 - 3.33). Conclusion:
      Current herd-immunity may not be sufficient to prevent future small-to-medium
      epidemics in Cabo Verde. Together with a small observation rate, these results
      highlight the need for rapid and integrated epidemiological, molecular and
      genomic surveillance to tackle forthcoming outbreaks of ZIKV and other
      arboviruses.

PMID- 29637010
TI  - A Nosocomial Outbreak of Clinical Sepsis in a Neonatal Care Unit (NCU) in Port-Au
      Prince Haiti, July 2014 - September 2015.
AB  - Introduction: Between July 2014 and September 2015, a neonatal care unit (NCU) in
      Port Au Prince, Haiti, experienced an outbreak of sepsis, most probably due to
      nosocomial transmission of Extended Beta Lactamase (ESBL) producing gram negative
      bacteria, included Klebsiella pneumoniae. Methods: We describe the
      epidemiological and microbiological activities performed as part of the outbreak
      investigation and the control measures implemented throughout this period.
      Results: During the study period 257 cases of sepsis were reported, of which 191
      died. The case fatality decreased from 100% in July 2014 to 24% in September 2015
      and could be attributed to an improvement in clinical management and strengthened
      infection prevention and control measures. Risk factors identified to be
      associated with having late onset sepsis (sepsis onset >48 hours after
      birth)(n=205/257, 79. included: all categories of birthweight lower than <2500g
      (p=<0.0001) and all categories of gestational age younger than 36 weeks
      (p=0.0002). Microbiological investigations confirmed that out of 32 isolates
      (N=55; 58%) that were positive for gram negative bacteria, 27 (89%) were due to
      K. pneumoniae and most of these were from single MLST type (ST37). Discussion :
      This outbreak highlighted the importance of epidemiological and microbiological
      surveillance during an outbreak of sepsis in a NCU in a low resource setting,
      including regular point prevalence surveys.

PMID- 29637012
TI  - Tele-yoga for Chronic Pain: Current Status and Future Directions.
AB  - Pain is a pervasive, debilitating disorder that is resistant to long-term
      pharmacological interventions. Although psychological therapies such as cognitive
      behavior therapy demonstrate moderate efficacy, many individuals continue to have
      ongoing difficulties following treatment. There is a current trend to establish
      complementary and integrative health interventions for chronic pain, for which
      yoga has been found to have exciting potential. Nevertheless, an important
      consideration within the field is accessibility to adequate care. Telehealth can
      be used to provide real-time interactive video conferencing leading to increased
      access to health care for individuals located remotely or who otherwise have
      difficulty accessing services, perhaps through issues of mobility or proximity of
      adequate services. This article assesses the current status and feasibility of
      implementing tele-yoga for chronic pain. Methodological limitations and
      recommendations for future research are discussed.

PMID- 29637013
TI  - Leadless Pacemaker: Report of the First Experience in Hawai'i.
AB  - We had the opportunity to implant the first leadless pacemakers in Hawai'i. This
      device represents a major change in pacemaker technology. This is a report of the
      first five cases and a review of the literature. All these devices were implanted
      via femoral venous access (versus conventional upper chest
      axillary/subclavian/cephalic routes), with an unique fixation mechanism allowing
      direct attachment to the ventricular myocardium (dispensing the usage of long
      transvenous electrode leads). The miniature generator can is over an order of
      magnitude smaller and lighter than the currently available ones. This article
      provides an understanding of the device design, implantation technique, the
      advantages and limitations, and the potential of this new pacemaker.

PMID- 29637011
TI  - Neurocysticercosis in Pregnancy.
AB  - The normal physiologic changes during pregnancy contribute to nutritional,
      metabolic, and immunologic adjustments, which can have an impact on the
      presentation of several diseases. New onset seizures during pregnancy and the
      postpartum can be attributed to several etiologies. Patient demographic data as
      well as personal and social histories are key in determining the etiology of new
      onset seizures. Neurocysticercosis (NCC), a commonly overlooked etiology, must be
      included in the differential diagnosis of patients with new onset seizures coming
      from NCC endemic areas. The diagnosis is based on a combination of clinical
      findings, exposure history, imaging, and serology. We present two cases of
      patients with NCC that became symptomatic during pregnancy or postpartum period.
      We will review the epidemiology, clinical manifestations, and management of NCC
      in pregnancy.

PMID- 29637014
TI  - Chuukese Patients, Dual Role Interpreters, and Confidentiality: Exploring Clinic
      Interpretation Services for Reproductive Health Patients.
AB  - This exploratory study analyzes limited English proficient (LEP) Chuukese
      patients' perspectives on dual-role interpreters in Guam and Chuuk. Methods
      included ethnographic observations of encounters with health care workers (HCWs)
      and 225 female Chuukese patients seeking reproductive healthcare in community
      health clinics: 126 women in Guam and 99 women in Chuuk. Ethnographic
      observations were supplemented by semi-structured interviews with 26 HCWs, and
      life history interviews with 15 Chuukese transnational migrant women. Notes from
      interview transcripts and observations were analyzed using critical interpretive
      and grounded theory. Findings demonstrated that Chuukese LEP patients need and at
      times want interpreters in order to understand their healthcare visits. In the
      absence of professional interpreters, ad-hoc interpreters (family interpreters
      and employees of the clinic) are an important resource. However, social and
      cultural concerns with community confidentiality influenced patient trust of
      staff interpreters. This lack of trust can limit access to health care overall,
      as some patients may avoid seeking care to prevent their confidential health
      information being disclosed. These complexities in interpretation must be
      considered in order for clinics to provide optimal care for the communities they
      serve.

PMID- 29637015
TI  - Medical School Hotline: New Research Grants Awarded in AY 2016-2017 at the John
      A. Burns School of Medicine.

PMID- 29637016
TI  - Insights in Public Health: Recognize, Retreat, and Report: Education and
      Community Partnerships Essential to Injury Prevention from Unexploded Ordnance
      across Hawaii's WWII Training Grounds.

PMID- 29637018
TI  - Density and population viability of coastal marten: a rare and geographically
      isolated small carnivore.
AB  - Pacific martens (Martes caurina humboldtensis) in coastal forests of Oregon and
      northern California in the United States are rare and geographically isolated,
      prompting a petition for listing under the Endangered Species Act. If listed,
      regulations have the potential to influence land-use decisions on public and
      private lands, but no estimates of population size, density, or viability of
      remnant marten populations are available for evaluating their conservation
      status. We used GPS and VHF telemetry and spatial mark-resight to estimate home
      ranges, density, and population size of Pacific martens in the Oregon Dunes
      National Recreation Area, central coast Oregon, USA. We then estimated population
      viability at differing levels of human-caused mortality (e.g., vehicle
      mortality). Marten home ranges were small on average (females = 0.8 km2, males
      1.5 km2) and density (1.13 martens/1 km2) was the highest reported for North
      American populations (M. caurina, M. americana). We estimated 71 adult martens
      (95% CRI [41-87]) across two subpopulations separated by a large barrier (Umpqua
      River). Using population viability analysis, extinction risk for a subpopulation
      of 30 martens, approximately the size of the subpopulation south of the Umpqua
      River, ranged from 32% to 99% with two or three annual human-caused mortalities
      within 30 years. Absent population expansion, limiting human-caused mortalities
      will likely have the greatest conservation impact.

PMID- 29637019
TI  - Including autapomorphies is important for paleontological tip-dating with
      clocklike data, but not with non-clock data.
AB  - Tip-dating, where fossils are included as dated terminal taxa in Bayesian dating
      inference, is an increasingly popular method. Data for these studies often come
      from morphological character matrices originally developed for non-dated, and
      usually parsimony, analyses. In parsimony, only shared derived characters
      (synapomorphies) provide grouping information, so many character matrices have an
      ascertainment bias: they omit autapomorphies (unique derived character states),
      which are considered uninformative. There has been no study of the effect of this
      ascertainment bias in tip-dating, but autapomorphies can be informative in model
      based inference. We expected that excluding autapomorphies would shorten the
      morphological branchlengths of terminal branches, and thus bias downwards the
      time branchlengths inferred in tip-dating. We tested for this effect using a
      matrix for Carboniferous-Permian eureptiles where all autapomorphies had been
      deliberately coded. Surprisingly, date estimates are virtually unchanged when
      autapomorphies are excluded, although we find large changes in morphological rate
      estimates and small effects on topological and dating confidence. We hypothesized
      that the puzzling lack of effect on dating was caused by the non-clock nature of
      the eureptile data. We confirm this explanation by simulating strict clock and
      non-clock datasets, showing that autapomorphy exclusion biases dating only for
      the clocklike case. A theoretical solution to ascertainment bias is computing the
      ascertainment bias correction (Mkparsinf), but we explore this correction in
      detail, and show that it is computationally impractical for typical datasets with
      many character states and taxa. Therefore we recommend that palaeontologists
      collect autapomorphies whenever possible when assembling character matrices.

PMID- 29637020
TI  - 2D versus 3D real time ultrasound with live xPlane imaging to visualize aortic
      and ductal arches: comparison between methods.
AB  - Background: The diagnosis of congenital heart defects is challenging, especially
      for what concerns conotruncal anomalies. Indeed, although the screening
      techniques of fetal cardiac anomalies have greatly improved, the detection rate
      of conotruncal anomalies still remains low due to the fact that they are
      associated with a normal four-chamber view. Therefore, the study aimed to compare
      real-time three-dimensional echocardiography with live xPlane imaging with two
      dimensional (2D) traditional imaging in visualizing ductal and aortic arches
      during routine echocardiography of the second trimester of gestation. Methods:
      This was an observational prospective study including 114 women with
      uncomplicated, singleton pregnancies. All sonographic studies were performed by
      two different operators, of them 60 by a first level operator, while 54 by a
      second level operator. A subanalysis was run in order to evaluate the feasibility
      and the time needed for the two procedures according to fetal spine position and
      operator's experience. Results: The measurements with 2D ultrasound were
      performed in all 114 echocardiographies, while live xPlane imaging was feasible
      in the 78% of the cases, and this was mainly due to fetal position. The time
      lapse needed to visualize aortic and ductal arches was significantly lower when
      using 2D ultrasound compared to live xPlane imaging (29.56 +/- 28.5 s vs. 42.5 +/
      38.1 s, P = 0.006 for aortic arch; 22.14 +/- 17.8 s vs. 37.1 +/- 33.8 s, P =
      0.001 for ductal arch), also when performing a subanalysis according to
      operators' experience (P < 0.05 for all comparisons). Feasibility of live xPlane
      proved to be correlated with the position of the fetal spine and the operator's
      experience. Discussion: To find a reproducible and standardized method to detect
      fetal heart defects may bring a great benefit for both patients and operators. In
      this scenario live xPlane imaging is a novel method to visualize ductal and
      aortic arches. We found that the position of the fetal spine may affect the
      feasibility of the method since, when the fetal back is anterior or transverse,
      the visualization of the correct view of three-vessels and trachea in order to
      set the reference line properly becomes more challenging. In addition, the fetal
      spine position influences the duration of the ultrasound examination. Regarding
      operator's skills and experience, in our study a first level operator was able to
      perform the complete 2D and xPlane examination in a lower number of cases
      compared to second level operators. In addition, the time required for the
      complete examination was higher for first level operators. This means that this
      technique is based on an adequate operators' expertise.

PMID- 29637021
TI  - Year-round monitoring reveals prevalence of fatal bird-window collisions at the
      Virginia Tech Corporate Research Center.
AB  - Collisions with glass are a serious threat to avian life and are estimated to
      kill hundreds of millions of birds per year in the United States. We monitored 22
      buildings at the Virginia Tech Corporate Research Center (VTCRC) in Blacksburg,
      Virginia, for collision fatalities from October 2013 through May 2015 and
      explored possible effects exerted by glass area and surrounding land cover on
      avian mortality. We documented 240 individuals representing 55 identifiable
      species that died due to collisions with windows at the VTCRC. The relative risk
      of fatal collisions at all buildings over the study period were estimated using a
      Bayesian hierarchical zero-inflated Poisson model adjusting for percentage of
      tree and lawn cover within 50 m of buildings, as well as for glass area. We found
      significant relationships between fatalities and surrounding lawn area (relative
      risk: 0.96, 95% credible interval: 0.93, 0.98) as well as glass area on buildings
      (RR: 1.30, 95% CI [1.05-1.65]). The model also found a moderately significant
      relationship between fatal collisions and the percent land cover of ornamental
      trees surrounding buildings (RR = 1.02, 95% CI [1.00-1.05]). Every building
      surveyed had at least one recorded collision death. Our findings indicate that
      birds collide with VTCRC windows during the summer breeding season in addition to
      spring and fall migration. The Ruby-throated Hummingbird (Archilochus colubris)
      was the most common window collision species and accounted for 10% of deaths.
      Though research has identified various correlates with fatal bird-window
      collisions, such studies rarely culminate in mitigation. We hope our study brings
      attention, and ultimately action, to address this significant threat to birds at
      the VTCRC and elsewhere.

PMID- 29637022
TI  - Longitudinal analysis of raccoon rabies in West Virginia, 2000-2015: a
      preliminary investigation.
AB  - Animal borne rabies virus is a source of infection in humans, and raccoons
      (Procyon lotor) are the primary terrestrial reservoir in West Virginia (WV). To
      assess the behavior and status of raccoon variant rabies virus (RRV) cases in WV,
      a longitudinal analysis for the period 2000-2015 was performed, using data
      provided by the state Bureau of Public Health. The analytic approach used was
      negative binomial regression, with exclusion of those counties that had not
      experienced RRV cases in the study period, and with further examination of those
      counties where oral rabies vaccine (ORV) baits had been distributed as compared
      with non-ORV counties. These analyses indicated that there had been a reduction
      in numbers of RRV positive animals over the study period, predominantly due to a
      decrease in raccoon infections. Non-raccoon hosts did not appear to have a
      similar decline, however. The rates of decline for the ORV zone were found to be
      significantly greater as compared to the non-ORV area. The study was limited by
      the lack of data for season or point location of animal collection, and by lack
      of surveillance effort data. Even so, this study has implications for the
      preventive measures currently being implemented, including expanded vaccination
      effort in domestic animals. Spatial analyses of RRV and further examination of
      the virus in non-raccoon hosts are warranted.

PMID- 29637023
TI  - Reinvestigating an enigmatic Late Cretaceous monocot: morphology, taxonomy, and
      biogeography of Viracarpon.
AB  - Angiosperm-dominated floras of the Late Cretaceous are essential for
      understanding the evolutionary, ecological, and geographic radiation of flowering
      plants. The Late Cretaceous-early Paleogene Deccan Intertrappean Beds of India
      contain angiosperm-dominated plant fossil assemblages known from multiple
      localities in central India. Numerous monocots have been documented from these
      assemblages, providing a window into an important but poorly understood time in
      their diversification. One component of the Deccan monocot diversity is the genus
      Viracarpon, known from anatomically preserved infructescences. Viracarpon was
      first collected over a century ago and has been the subject of numerous studies.
      However, resolution of its three-dimensional (3D) morphology and anatomy, as well
      as its taxonomic affinities, has remained elusive. In this study we investigated
      the morphology and taxonomy of genus Viracarpon, combining traditional
      paleobotanical techniques and X-ray micro-computed tomography (MUCT). Re
      examination of type and figured specimens, 3D reconstructions of fruits, and
      characterization of structures in multiple planes of section using MUCT data
      allowed us to resolve conflicting interpretations of fruit morphology and
      identify additional characters useful in refining potential taxonomic affinities.
      Among the four Viracarpon species previously recognized, we consider two to be
      valid (Viracarponhexaspermum and Viracarponelongatum), and the other two to be
      synonyms of these. Furthermore, we found that permineralized infructescences of
      Coahuilocarpon phytolaccoides from the late Campanian of Mexico correspond
      closely in morphology to V. hexaspermum. We argue that Viracarpon and
      Coahuilocarpon are congeneric and provide the new combination, Viracarpon
      phytolaccoides (Cevallos-Ferriz, Estrada-Ruiz & Perez-Hernandez) Matsunaga, S.Y.
      Smith, & Manchester comb. nov. The significant geographic disjunction between
      these two occurrences indicates that the genus Viracarpon was widespread and may
      be present in other Late Cretaceous assemblages. Viracarpon exhibits character
      combinations not present in any extant taxa and its affinities remain unresolved,
      possibly representing an extinct member of Alismatales. The character mosaic
      observed in Viracarpon and the broad distribution of the genus provide new data
      relevant to understanding early monocot evolution and suggest that the (thus far)
      largely invisible Late Cretaceous monocot diversification was characterized by
      enigmatic and/or stem taxa.

PMID- 29637024
TI  - Genomic analyses of Northern snakehead (Channa argus) populations in North
      America.
AB  - Background: The introduction of northern snakehead (Channa argus; Anabantiformes:
      Channidae) and their subsequent expansion is one of many problematic biological
      invasions in the United States. This harmful aquatic invasive species has become
      established in various parts of the eastern United States, including the Potomac
      River basin, and has recently become established in the Mississippi River basin
      in Arkansas. Effective management of C. argus and prevention of its further
      spread depends upon knowledge of current population structure in the United
      States. Methods: Novel methods for invasive species using whole genomic scans
      provide unprecedented levels of data, which are able to investigate fine scale
      differences between and within populations of organisms. In this study, we
      utilize 2b-RAD genomic sequencing to recover 1,007 single-nucleotide polymorphism
      (SNP) loci from genomic DNA extracted from 165 C. argus individuals: 147
      individuals sampled along the East Coast of the United States and 18 individuals
      sampled throughout Arkansas. Results: Analysis of those SNP loci help to resolve
      existing population structure and recover five genetically distinct populations
      of C. argus in the United States. Additionally, information from the SNP loci
      enable us to begin to calculate the long-term effective population size ranges of
      this harmful aquatic invasive species. We estimate long-term Ne to be 1,840,000
      18,400,000 for the Upper Hudson River basin, 4,537,500-45,375,000 for the Lower
      Hudson River basin, 3,422,500-34,225,000 for the Potomac River basin, 2,715,000
      7,150,000 for Philadelphia, and 2,580,000-25,800,000 for Arkansas populations.
      Discussion and Conclusions: This work provides evidence for the presence of more
      genetic populations than previously estimated and estimates population size,
      showing the invasive potential of C. argus in the United States. The valuable
      information gained from this study will allow effective management of the
      existing populations to avoid expansion and possibly enable future eradication
      efforts.

PMID- 29637025
TI  - The neglected bee trees: European beech forests as a home for feral honey bee
      colonies.
AB  - It is a common belief that feral honey bee colonies (Apis mellifera L.) were
      eradicated in Europe through the loss of habitats, domestication by man and
      spread of pathogens and parasites. Interestingly, no scientific data are
      available, neither about the past nor the present status of naturally nesting
      honeybee colonies. We expected near-natural beech (Fagus sylvatica L.) forests to
      provide enough suitable nest sites to be a home for feral honey bee colonies in
      Europe. Here, we made a first assessment of their occurrence and density in two
      German woodland areas based on two methods, the tracing of nest sites based on
      forager flight routes (beelining technique), and the direct inspection of
      potential cavity trees. Further, we established experimental swarms at forest
      edges and decoded dances for nest sites performed by scout bees in order to study
      how far swarms from beekeeper-managed hives would potentially move into a forest.
      We found that feral honey bee colonies regularly inhabit tree cavities in near
      natural beech forests at densities of at least 0.11-0.14 colonies/km2. Colonies
      were not confined to the forest edges; they were also living deep inside the
      forests. We estimated a median distance of 2,600 m from the bee trees to the next
      apiaries, while scout bees in experimental swarms communicated nest sites in
      close distances (median: 470 m). We extrapolate that there are several thousand
      feral honey bee colonies in German woodlands. These have to be taken in account
      when assessing the role of forest areas in providing pollination services to the
      surrounding land, and their occurrence has implications for the species'
      perception among researchers, beekeepers and conservationists. This study
      provides a starting point for investigating the life-histories and the ecological
      interactions of honey bees in temperate European forest environments.

PMID- 29637026
TI  - Predicting Pinus monophylla forest cover in the Baja California Desert by remote
      sensing.
AB  - The Californian single-leaf pinyon (Pinus monophylla var. californiarum), a
      subspecies of the single-leaf pinyon (the world's only one-needled pine),
      inhabits semi-arid zones of the Mojave Desert (southern Nevada and southeastern
      California, US) and also of northern Baja California (Mexico). This tree is
      distributed as a relict subspecies, at elevations of between 1,010 and 1,631 m in
      the geographically isolated arid Sierra La Asamblea, an area characterized by
      mean annual precipitation levels of between 184 and 288 mm. The aim of this
      research was (i) to estimate the distribution of P. monophylla var. californiarum
      in Sierra La Asamblea by using Sentinel-2 images, and (ii) to test and describe
      the relationship between the distribution of P. monophylla and five topographic
      and 18 climate variables. We hypothesized that (i) Sentinel-2 images can be used
      to predict the P. monophylla distribution in the study site due to the finer
      resolution (*3) and greater number of bands (*2) relative to Landsat-8 data,
      which is publically available free of charge and has been demonstrated to be
      useful for estimating forest cover, and (ii) the topographical variables aspect,
      ruggedness and slope are particularly important because they represent important
      microhabitat factors that can determine the sites where conifers can become
      established and persist. An atmospherically corrected a 12-bit Sentinel-2A MSI
      image with 10 spectral bands in the visible, near infrared, and short-wave
      infrared light region was used in combination with the normalized differential
      vegetation index (NDVI). Supervised classification of this image was carried out
      using a backpropagation-type artificial neural network algorithm. Stepwise
      multiple linear binominal logistical regression and Random Forest classification
      including cross validation were used to model the associations between
      presence/absence of P. monophylla and the five topographical and 18 climate
      variables. Using supervised classification of Sentinel-2 satellite images, we
      estimated that P. monophylla covers 6,653 +/- 319 ha in the isolated Sierra La
      Asamblea. The NDVI was one of the variables that contributed most to the
      prediction and clearly separated the forest cover (NDVI > 0.35) from the other
      vegetation cover (NDVI < 0.20). Ruggedness was the most influential environmental
      predictor variable, indicating that the probability of occurrence of P.
      monophylla was greater than 50% when the degree of ruggedness terrain ruggedness
      index was greater than 17.5 m. The probability of occurrence of the species
      decreased when the mean temperature in the warmest month increased from 23.5 to
      25.2  degrees C. Ruggedness is known to create microclimates and provides shade
      that minimizes evapotranspiration from pines in desert environments.
      Identification of the P. monophylla stands in Sierra La Asamblea as the most
      southern populations represents an opportunity for research on climatic tolerance
      and community responses to climate variability and change.

PMID- 29637027
TI  - Expression profiles of TRPV1, TRPV4, TLR4 and ERK1/2 in the dorsal root
      ganglionic neurons of a cancer-induced neuropathy rat model.
AB  - Background: The spread of tumors through neural routes is common in several types
      of cancer in which patients suffer from a moderate-to-severe neuropathy, neural
      damage and a distorted quality of life. Here we aim to examine the expression
      profiles of transient receptor potential vanilloid 1 (TRPV1) and of transient
      receptor potential vanilloid 4 (TRPV4), toll-like receptor 4 (TLR4) and
      extracellular signal-regulated kinase (ERK1/2), and to assess the possible
      therapeutic strategies through blockade of transient receptor potential (TRP)
      channels. Methods: Cancer was induced within the sciatic nerves of male
      Copenhagen rats, and tissues from dorsal root ganglia (DRG) were collected and
      used for measurements of immunofluorescence and Western blotting. The TRPV1
      antagonist capsazepine, the selective TRPV4 antagonist HC-067047 and the calcium
      ions inhibitor ruthenium red were used to treat thermal and/or mechanical
      hyperalgesia. Results: Transient receptor potential vanilloid 1 showed a lower
      expression in DRGs on days 7 and 14. The expression of TRPV4, TLR4 and ERK1/2
      showed an increase on day 3 then a decrease on days 7 and 14. TRPV1 and TLR4 as
      well as TRPV4 and ERK1/2 co-existed on the same neuronal cells. The neuropathic
      pain was reversed in dose-dependent manners by using the TRP antagonists and the
      calcium ions inhibitor. Conclusion: The decreased expression of TRPV1 and TRPV4
      is associated with high activation. The increased expression of TLR4 and ERK1/2
      reveals earlier immune response and tumor progression, respectively, and their
      ultimate decrease is an indicator of nerve damage. We studied the possible role
      of TRPV1 and TRPV4 in transducing cancer-induced hyperalgesia. The possible
      treatment strategies of cancer-induced thermal and/or mechanical hyperalgesia
      using capsazepine, HC-067047 and ruthenium red are examined.

PMID- 29637028
TI  - Surface display for metabolic engineering of industrially important acetic acid
      bacteria.
AB  - Acetic acid bacteria have unique metabolic characteristics that suit them for a
      variety of biotechnological applications. They possess an arsenal of membrane
      bound dehydrogenases in the periplasmic space that are capable of regiospecific
      and enantioselective partial oxidations of sugars, alcohols, and polyols. The
      resulting products are deposited directly into the medium where they are easily
      recovered for use as pharmaceutical precursors, industrial chemicals, food
      additives, and consumer products. Expression of extracytoplasmic enzymes to
      augment the oxidative capabilities of acetic acid bacteria is desired but is
      challenging due to the already crowded inner membrane. To this end, an original
      surface display system was developed to express recombinant enzymes at the outer
      membrane of the model acetic acid bacterium Gluconobacter oxydans. Outer membrane
      porin F (OprF) was used to deliver alkaline phosphatase (PhoA) to the cell
      surface. Constitutive high-strength p264 and moderate-strength p452 promoters
      were used to direct expression of the surface display system. This system was
      demonstrated for biocatalysis in whole-cell assays with the p264 promoter having
      a twofold increase in PhoA activity compared to the p452 promoter. Proteolytic
      cleavage of PhoA from the cell surface confirmed proper delivery to the outer
      membrane. Furthermore, a linker library was constructed to optimize surface
      display. A rigid (EAAAK)1 linker led to the greatest improvement, increasing PhoA
      activity by 69%. This surface display system could be used both to extend the
      capabilities of acetic acid bacteria in current biotechnological processes, and
      to broaden the potential of these microbes in the production of value-added
      products.

PMID- 29637030
TI  - An Alternative Myoelectric Pattern Recognition Approach for the Control of Hand
      Prostheses: A Case Study of Use in Daily Life by a Dysmelia Subject.
AB  - The functionality of upper limb prostheses can be improved by intuitive control
      strategies that use bioelectric signals measured at the stump level. One such
      strategy is the decoding of motor volition via myoelectric pattern recognition
      (MPR), which has shown promising results in controlled environments and more
      recently in clinical practice. Moreover, not much has been reported about daily
      life implementation and real-time accuracy of these decoding algorithms. This
      paper introduces an alternative approach in which MPR allows intuitive control of
      four different grips and open/close in a multifunctional prosthetic hand. We
      conducted a clinical proof-of-concept in activities of daily life by constructing
      a self-contained, MPR-controlled, transradial prosthetic system provided with a
      novel user interface meant to log errors during real-time operation. The system
      was used for five days by a unilateral dysmelia subject whose hand had never
      developed, and who nevertheless learned to generate patterns of myoelectric
      activity, reported as intuitive, for multi-functional prosthetic control. The
      subject was instructed to manually log errors when they occurred via the user
      interface mounted on the prosthesis. This allowed the collection of information
      about prosthesis usage and real-time classification accuracy. The assessment of
      capacity for myoelectric control test was used to compare the proposed approach
      to the conventional prosthetic control approach, direct control. Regarding the
      MPR approach, the subject reported a more intuitive control when selecting the
      different grips, but also a higher uncertainty during proportional continuous
      movements. This paper represents an alternative to the conventional use of MPR,
      and this alternative may be particularly suitable for a certain type of amputee
      patients. Moreover, it represents a further validation of MPR with dysmelia
      cases.

PMID- 29637029
TI  - Histogram-Based Features Selection and Volume of Interest Ranking for Brain PET
      Image Classification.
AB  - Positron emission tomography (PET) is a molecular medical imaging modality which
      is commonly used for neurodegenerative diseases diagnosis. Computer-aided
      diagnosis, based on medical image analysis, could help quantitative evaluation of
      brain diseases such as Alzheimer's disease (AD). A novel method of ranking the
      effectiveness of brain volume of interest (VOI) to separate healthy control from
      AD brains PET images is presented in this paper. Brain images are first mapped
      into anatomical VOIs using an atlas. Histogram-based features are then extracted
      and used to select and rank VOIs according to the area under curve (AUC)
      parameter, which produces a hierarchy of the ability of VOIs to separate between
      groups of subjects. The top-ranked VOIs are then input into a support vector
      machine classifier. The developed method is evaluated on a local database image
      and compared to the known selection feature methods. Results show that using AUC
      outperforms classification results in the case of a two group separation.

PMID- 29637031
TI  - Pain Perception and the Opioid Receptor Delta 1.
AB  - Genetic factors play an integral role in the perception of pain, and studies have
      only recently begun to explore the degree to which these factors affect clinical
      decisions. The process of prescribing opioids is greatly influenced by an
      individual's pain perception, which can vary based on several factors including
      genetic variation. Opioid receptor delta 1 (OPRD1) plays a significant role in
      the perception of both pain and its relief via opioids, and it shows significant
      variability between individuals. Herein, we discuss the nature of the OPRD1
      receptor and the value of further research into its effects, particularly in the
      realm of pain management.

PMID- 29637032
TI  - Sleep Abnormalities Among Patients With and Without Diabetes Using Pittsburg
      Sleep Quality Index and Epworth Sleepiness Scale.
AB  - Introduction Diabetes has a great influence on sleep patterns. Several hormonal
      mechanisms are disrupted in patients with diabetes and, hence, affect their sleep
      patterns. Sleep disturbances further worsen the state of the disease itself.
      Method In this cross-sectional study, we collected data from 50 healthy adults
      and 50 patients diagnosed with type 2 diabetes mellitus without comorbidities.
      Study participants were asked to complete the Pittsburgh Sleep Quality Index
      (PSQI) and Epworth Sleepiness Scale (ESS) surveys. Results The mean PSQI score
      was 8.64 +/- 3.96 for patients with type 2 diabetes and 4.24 +/- 2.72 for
      patients without diabetes. The mean Epworth Sleepiness score was 6.3 +/- 5.29
      among patients with diabetes and 1.94 +/- 2.34 for patients without diabetes.
      Conclusion The early diagnosis and management of sleep problems can help maintain
      target blood glucose levels and may help impede the future development of
      complications.

PMID- 29637033
TI  - Metformin-Induced Lactic Acidosis: A Case Study.
AB  - Metformin is the first line management for patients with Type 2 diabetes
      mellitus. Metformin-induced lactic acidosis (MALA) is a severe side effect of
      metformin in high doses. However, there have not been many reported cases of
      MALA. The threshold metformin concentration needed to induce lactic acidosis is
      still not fully understood. It is important for physicians to measure metformin
      levels upon admission in Type 2 diabetes patients who take metformin and present
      with suspected lactic acidosis. We present a case of a 40-year-old Caucasian male
      who presented with severe lactic acidosis shortly after overdosing on metformin.

PMID- 29637034
TI  - Lymphocytic Esophagitis: A Rare Disease on the Rise.
AB  - Lymphocytic esophagitis is a rare, poorly understood disease. This case report
      presents a patient with a history of squamous cell carcinoma of the tongue who
      presented with dysphagia. He received esophageal dilation that unfortunately
      resulted in perforation. Biopsies showed lymphocytic esophagitis. There are very
      few cases in the literature describing perforation in lymphocytic esophagitis. In
      addition, management and treatment have been challenging for physicians; however,
      this case represents a complete symptomatic improvement in four to six weeks with
      a proton pump inhibitor.

PMID- 29637035
TI  - Curated Collections for Educators: Five Key Papers about Residents as Teachers
      Curriculum Development.
AB  - The Accreditation Council for Graduate Medical Education (ACGME) requires
      residency programs to prepare residents to teach and assess medical students and
      other learners. In order to achieve this, many programs develop formal residents
      as teachers (RAT) curricula. Medical educators may seek the guidance of
      previously published literature during the development of RAT programs at their
      institutions. The authors sought to identify key articles published on the
      subject of RAT programs over the last 10 years. The authors utilized a formal
      literature search with the help of a medical librarian and identified additional
      articles from virtual discussions among the author group and an open call for
      articles on Twitter using the hashtag #MedEd. Virtual discussions occurred within
      an online community of practice, the Academic Life in Emergency Medicine (ALiEM)
      Faculty Incubator. The lead author conducted a four-round modified Delphi process
      among the author group in order to narrow the broad article list to five key
      articles on RAT programs. The authors summarize each article and provide
      considerations for junior faculty as well as faculty developers. Curriculum
      development and program evaluation should utilize established frameworks and
      evidence-based approaches. The papers identified by this Delphi process will help
      faculty use best practices when creating or revising new RAT curriculum. In
      addition, faculty tasked with guiding junior faculty in this process or creating
      faculty development programs around curriculum development will find these
      articles to be a great resource for building content.

PMID- 29637036
TI  - A Mild Version of Danon Disease Caused by a Newly Recognized Mutation in the
      Lysosome-associated Membrane Protein-2 Gene.
AB  - We present the case of a patient with dilated cardiomyopathy caused by a novel
      mutation in the lysosome-associated membrane protein-2 (LAMP-2) gene. Patients
      with pathogenic mutations of this gene typically suffer from Danon disease - a
      condition that leads to cognitive decline, severe skeletal myopathy, and severe
      hypertrophic cardiomyopathy. Our patient's presentation and clinical course,
      however, is different and much less severe than other patients with this disease.
      He did not suffer from neurologic and musculoskeletal complications. He is also
      possibly the longest-known survivor of this disease without a heart transplant.
      This disease is unfamiliar to many physicians, and our case highlights the
      importance of an awareness of this disorder, particularly because of its
      implications for both the patient and his family.

PMID- 29637037
TI  - Determining the Optimal Length and Safety of Pedicle Screws in the T12 Vertebra:
      A Morphometric Study.
AB  - INTRODUCTION: Despite the developments in implant technology and imaging methods
      and the advances in surgical techniques, there are still potential problems and
      complications of transpedicular screw application. This is a morphometric study
      to examine the proximity of the T12 vertebra to the thoracic aorta. Our aim was
      to define the appropriate length of the pedicle screw to be used in the 12th
      thoracic vertebra, using computed tomography (CT) data. METHODS: Randomly
      selected cases from the same ethnic group in a specific age group were examined
      in terms of the length from the anterior vertebral body and the screw entry point
      of the T12 vertebra to the thoracic aorta. In light of these data, a statistical
      analysis was made for the selection of the most appropriate screw length.
      RESULTS: A statistically significant difference was detected in the distance from
      the T12 left screw entry point to the aorta between males and females (p=0.001).
      No statistically significant correlation was found between age and the distance
      between the left screw entry point and the aorta (p=0.105). Also, no
      statistically significant difference was detected between the T12 vertebral body
      aorta distance in males and in females (p=0.212). The relationship between the
      shortest aorta-vertebral body distance and age was not statistically significant
      (p=0.7). Similarly, there was no statistically significant difference between the
      left screw entry point-aorta distance and the aorta-vertebral body shortest
      distance (p=0.731). CONCLUSIONS: Significant differences were observed between
      males and females in terms of the distance between the T12 vertebra left screw
      entry point and the thoracic aorta (p=0.001). Thus, we can assert the need for
      the preoperative evaluation of patients with computed tomography in selecting the
      appropriate screw length and avoiding complications.

PMID- 29637038
TI  - Clinicopathological Behavior and Oncological Outcomes of Malignant Parotid Tumors
      in a Pakistani Population.
AB  - Introduction The incidence of salivary gland tumors is influenced by geographical
      and racial factors resulting in diverse histology.  While salivary gland tumors
      account for a low proportion of head and neck cancers, most malignant tumors of
      the salivary gland are located in the parotid gland. The goals of this study are
      to describe the clinicopathological behavior of malignant parotid tumors and
      explore oncological outcomes related to survival in our Pakistani tertiary care
      cancer hospital. Methods We conducted a retrospective analysis of 209 patients
      diagnosed with malignant parotid tumors from 2004 to 2016. Data such as
      demographics, age, gender, histology, grade, clinical and pathological stage,
      surgical treatment types and adjuvant modalities used were analyzed using SPSS
      software version 20. We used Kaplan Meier curves to analyze survival data.
      Results The median patient age at diagnosis was 40 years, and the ratio of men to
      women was 1.2:1. Mucoepidermoid carcinoma was the most common histological
      variant (with a 50% incidence rate) followed by adenoid cystic carcinoma (13%),
      and adenocarcinoma (10%). Histology has further categorized these malignant
      tumors into low (34%), intermediate (28%), and high (21% ) grades. The American
      Joint Committee on Cancer, seventh edition, clinical staging was Stage I (21%),
      II (28%), III (15%), and IV (34%). The 5-year survival was 68%, and the 10-year
      survival was 45%. Conclusion Mucoepidermoid carcinoma is the most common
      malignant parotid histology in our patient population. Advanced age, increased T
      stage (size > 4 cm), high-grade histology, and cervical nodal involvement
      decrease overall survival. Open biopsies, piecemeal excisions, and delayed
      presentation for radiotherapy post-surgery may also have role in adverse outcomes
      in these malignancies.

PMID- 29637039
TI  - Catheter-Related Candida Endocarditis on the Right Atrial Septum - A Case Report.
AB  - The use of subcutaneous catheter devices has increased over the past two decades
      along with its associated infections. One of the complications is infective
      endocarditis (IE), which usually occurs on the valves of the heart. However, IE
      can rarely occur on the atrial septal wall. The most common pathogens associated
      with catheter-related IE are staphylococcus bacteria, and it is rarely caused by
      fungi. We present a case of a 75-year-old Caucasian female with infective
      endocarditis located on the right side of the atrial septum, caused by Candida
      albicans due to the use of a subcutaneous catheter port. We will discuss the
      diagnostic criteria and treatment plan for this patient and other treatment
      options available for these cases. To our knowledge, a similar case was reported
      in Brazil, but this is the first reported case in the United States of catheter
      related infective endocarditis of the right atrial septal wall due to Candida
      albicans.

PMID- 29637040
TI  - Atypical Colonoscopic Presentation of Lymphocytic Colitis Mimicking Hyperplastic
      Polyposis Syndrome.
AB  - Lymphocytic colitis is a chronic inflammatory disease of colon usually presented
      in middle age female as chronic watery diarrhea. Diagnosis is made on biopsy as
      colonoscopy usually revealed normal appearing colonic mucosa. We present here an
      unusual case of a 25-year-old female with past medical history of asthma was
      evaluated for one year of non-bloody watery diarrhea. The symptoms started after
      a course of antibiotics for upper respiratory tract infection a year back. The
      serum chemistries, including liver enzymes, were unremarkable. Stool culture,
      ova, and parasites were unremarkable. Stool Clostridium difficile was also
      negative. Celiac disease antibodies were unremarkable. Stool occult blood test
      was positive. The patient underwent colonoscopy for the evaluation of chronic
      diarrhea and revealed multiple polyps throughout the colon with inflamed surfaces
      which were biopsied. The concern was for hyperplastic polyposis syndrome. Genetic
      testing for adenomatous polyposis gene was done and came back negative. Biopsy
      from polyps revealed lymphocytic colitis. The patient was started on budesonide
      which resulted in marked improvement in her symptoms. Our case highlighted an
      atypical endoscopic finding of lymphocytic colitis which mimic hyperplastic
      polyposis syndrome.

PMID- 29637041
TI  - Delayed Splenic Rupture Resulting in Massive Intraperitoneal Hemorrhage Post
      Ambulatory-Related Injury.
AB  - Delayed splenic rupture, once thought to be unusual, but now growing in
      incidence, is an issue that could potentiate severe morbidity and mortality to
      patients, regardless of the severity of the trauma. This case report presents one
      instance of delayed splenic rupture following minor trauma and discusses the need
      for further investigation in the management of this condition. A middle-aged,
      hypotensive male presented to the emergency department (ED) with signs of an
      acute abdomen following a syncopal episode, with successful resuscitation upon
      arrival. Computed tomography (CT) revealed fluid in the gastrohepatic ligament,
      as well as the right pericolic gutter, along with findings suggestive of a
      perforated peptic ulcer. General surgery was consulted, and an exploratory
      laparotomy was performed. However, during exploration, no such perforation was
      found. A large amount of blood was visualized in the left upper quadrant. The
      spleen was mobilized, and inspection revealed a posterior rupture, resulting in a
      splenectomy and subsequent hemostasis by the surgical team. The post-operative
      period was uneventful, with the patient revealing a previous fall onto a concrete
      floor two weeks prior to presentation to the ED. A pathological examination of
      the spleen revealed capsular tear with focal congestion and hemorrhage. It is the
      goal of this report to highlight the morbidity and mortality that occur after
      delayed splenic rupture, even with minor traumatic events. Current guidelines
      suggest nonoperative management of splenic injury in stable patients with low
      grade splenic injuries after blunt abdominal trauma. However, with the varied
      presentation and difficulty in the assessment of delayed splenic rupture,
      patients may be exposed to undue risks with current recommendations on the
      management of splenic injuries. Further research is needed to find the best
      practice in managing, and possibly preventing, delayed splenic rupture in
      patients presenting with an acute abdomen or abdominal trauma.

PMID- 29637042
TI  - The impact of cloud vertical profile on liquid water path retrieval based on the
      bispectral method: A theoretical study based on large-eddy simulations of shallow
      marine boundary layer clouds.
AB  - Passive optical retrievals of cloud liquid water path (LWP), like those
      implemented for Moderate Resolution Imaging Spectroradiometer (MODIS), rely on
      cloud vertical profile assumptions to relate optical thickness (tau) and
      effective radius (re ) retrievals to LWP. These techniques typically assume that
      shallow clouds are vertically homogeneous; however, an adiabatic cloud model is
      plausibly more realistic for shallow marine boundary layer cloud regimes. In this
      study a satellite retrieval simulator is used to perform MODIS-like satellite
      retrievals, which in turn are compared directly to the large-eddy simulation
      (LES) output. This satellite simulator creates a framework for rigorous
      quantification of the impact that vertical profile features have on LWP
      retrievals, and it accomplishes this while also avoiding sources of bias present
      in previous observational studies. The cloud vertical profiles from the LES are
      often more complex than either of the two standard assumptions, and the favored
      assumption was found to be sensitive to cloud regime (cumuliform/stratiform).
      Confirming previous studies, drizzle and cloud top entrainment of dry air are
      identified as physical features that bias LWP retrievals away from adiabatic and
      toward homogeneous assumptions. The mean bias induced by drizzle-influenced
      profiles was shown to be on the order of 5-10 g/m2. In contrast, the influence of
      cloud top entrainment was found to be smaller by about a factor of 2. A
      theoretical framework is developed to explain variability in LWP retrievals by
      introducing modifications to the adiabatic re profile. In addition to analyzing
      bispectral retrievals, we also compare results with the vertical profile
      sensitivity of passive polarimetric retrieval techniques.

PMID- 29637043
TI  - The Effect of Intravenous Infusion of Dexmedetomidine to Prevent Bleeding During
      Functional Endoscopic Sinus Surgery: A Clinical Trial.
AB  - Background: Bleeding during surgery can lead to serious complications. Methods
      and drugs to control bleeding are always important both for the surgeon and
      anesthesiologist, especially in endoscopic procedures. A lot of efforts are made
      to optimize the surgical conditions for functional endoscopic sinus surgery.
      Induced hypotension is widely advocated to prevent bleeding and consequently to
      improve the quality of an operation . Amongst the pharmacological agents,
      dexmedetomidine is the most recently introduced drug to provide hypotensive
      anesthesia during functional endoscopic sinus surgery. Objectives: The current
      study aimed at investigating the effects of intravenous infusion of
      dexmedetomidine on bleeding, nausea, awakening time, and other intravenous
      anesthetic doses during functional endoscopic sinus surgery. Methods: Sixty
      patients aged 16 to 60 years with American society of anesthesiologists (ASA)
      class I or II in Imam Khomeini hospital of Ahvaz, Iran, who were the candidate
      for the elective functional endoscopic sinus surgery were enrolled in the current
      double-blind clinical trial. They were randomly divided into 2 groups: group D
      (receiving dexmedetomidine), and group N (receiving normal saline). Sampling was
      based on the block randomization method. In group D, a 1-MUg/kg dexmedetomidine
      was injected during 10 minutes just before the induction. Then, 0.5 ug/ kg/ hour
      infusion was started. Both groups had the same induction and maintenance method
      as well as the drugs administered for general anesthesia induction. For
      maintenance, the patients received O2 50%: N2O 50% and 100 MUg/kg/minute of
      propofol and 0.2 MUg/kg/minute of remifentanil. In group N, instead of
      dexmedetomidine in bolus and maintenance, normal saline was used with the same
      volume. Mean arterial pressure was maintained between 65 to 75 mmHg. The
      incidence of bleeding, nausea and vomiting after surgery, the amount of
      maintenance drugs, and awakening time were recorded in a checklist. Results: The
      intravenous use of dexmedetomidine significantly reduced the amount of bleeding
      (P < 0.0001); in addition, the need for opioids (P < 0.0001) and intravenous
      anesthetics significantly decreased (P = 0.001). Awakening time was significantly
      longer (P = 0.001), but its effect on postoperative nausea and vomiting was not
      significant (P = 0.052). Conclusions: The current study showed that although
      propofol and remifentanil compounds can control hemodynamic state, but
      intravenous infusion of dexmedetomidine during the functional endoscopic sinus
      surgery reduced the amount of bleeding more significantly. It also reduced the
      dosage of maintenance drugs.

PMID- 29637044
TI  - Which Ultrasound-Guided Sciatic Nerve Block Strategy Works Faster? Prebifurcation
      or Separate Tibial-Peroneal Nerve Block? A Randomized Clinical Trial.
AB  - Background: Peripheral nerve block is an accepted method in lower limb surgeries
      regarding its convenience and good tolerance by the patients. Quick performance
      and fast sensory and motor block are highly demanded in this method. The aim of
      the present study was to compare 2 different methods of sciatic and tibial
      peroneal nerve block in lower limb surgeries in terms of block onset. Methods: In
      this clinical trial, 52 candidates for elective lower limb surgery were randomly
      divided into 2 groups: sciatic nerve block before bifurcation (SG; n = 27) and
      separate tibial-peroneal nerve block (TPG; n = 25) under ultrasound plus nerve
      stimulator guidance. The mean duration of block performance, as well as complete
      sensory and motor block, was recorded and compared between the groups. Results:
      The mean duration of complete sensory block in the SG and TPG groups was 35.4 +/-
      4.1 and 24.9 +/- 4.2 minutes, respectively, which was significantly lower in the
      TPG group (P = 0.001). The mean duration of complete motor block in the SG and
      TPG groups was 63.3 +/- 4.4 and 48.4 +/- 4.6 minutes, respectively, which was
      significantly lower in the TPG group (P = 0.001). No nerve injuries, paresthesia,
      or other possible side effects were reported in patients. Conclusions: According
      to the present study, it seems that TPG shows a faster sensory and motor block
      than SG.

PMID- 29637045
TI  - Commentary: Induction of Dormancy in Hypoxic Human Papillomavirus-Positive Cancer
      Cells.

PMID- 29637046
TI  - Endotyping of Chronic Rhinosinusitis With and Without Polyp Using Transcription
      Factor Analysis.
AB  - Inflammation of the nose and paranasal sinus or rhinosinusitis (RS) is a
      significant global health problem that is both very common and very costly to
      treat. Previous reports reveal variability in histology and mechanism of
      inflammation in patients with chronic rhinosinusitis with and without polyp
      (CRScNP and CRSsNP, respectively). There are various methods and hypothesis that
      try to explain this variability. Accordingly, the aim of this study was to
      investigate the incidence of each type of sinonasal inflammation among patients
      diagnosed with CRScNP or CRSsNP using transcription factor analysis (TFA). This
      study included mucosa specimens from nose/paranasal sinuses from patients with
      chronic rhinitis (CR), CRSsNP, or CRScNP that were obtained at the Department of
      Otorhinolaryngology, Faculty of Medicine Siriraj Hospital, Mahidol University,
      Bangkok, Thailand during the June 2009 to May 2012 study period. TFA was employed
      to measure the following transcription factors: T-box transcription factor (T
      bet) for Th1, GATA binding protein 3 (GATA-3) for Th2, retinoic acid-related
      orphan receptor C (RORC) for Th17, and forkhead box P3 (FOXP3) for Treg. Forty
      one subjects (22 males, 19 females) were enrolled, with a mean age of 45.93 +/-
      13 years. Twenty-six patients were diagnosed with CRScNP, 7 with CRSsNP, and 8
      with CR (controls). The majority of CRScNP specimens (76.9%) had eosinophil count
      greater than 100 cells/high-power field (HPF). Mean eosinophil count was 930.08
      +/- 1,399 cells/HPF (range: 17-5,570). Th2 transcription factor (GATA-3) was
      statistically significantly higher in the CRScNP group than in the CRS and
      control groups (p < 0.001); whereas, Treg transcription factor (FOXP3) was
      statistically significantly lower in the CRScNP group than in the CRSsNP and
      control groups (p < 0.001). The transcription factors for Th1 and Th17 (T-bet and
      RORC, respectively) were not significantly different among the three groups. The
      result of transcription factor analysis revealed hyperfunction of Th2 in patients
      with CRScNP, which might result in hypereosinophilic infliltration in the polyps.
      One explanation for this finding is the decreased activity of Treg. Although
      environment-host interaction is the most probable hypothesis, the etiology of
      aberrant adaptive immunity needs to be elucidated.

PMID- 29637047
TI  - Epidemiological and Genetic Characteristics of Rabies Virus Transmitted Through
      Organ Transplantation.
AB  - In January 2016, two patients died of rabies after receiving kidney transplants
      from a common organ donor at a hospital in Changsha, Hunan, China. The medical
      records, epidemiological data of the organ donor, two kidney and a liver
      recipients were reviewed. Intravitam saliva samples of the two kidney recipients
      were tested for rabies virus (RABV) using real-time RT-PCR, and the nucleoprotein
      (N) gene was amplified and sequenced by Sanger sequencing. Whole genome sequences
      were analyzed using next-generation sequencing. The N genes of the two kidney
      recipients showed 100% nucleic acid identity. Phylogenetic analysis of the
      complete genome, N and glycoprotein (G) genes indicated that the RABV was
      homologous with dog isolates from the Hunan province and belong to the China I
      lineage, which is widespread in China. The organ donor was a 22-month-old boy who
      died from unknown acute progressive encephalitis. After undergoing sub
      hypothermia hibernation therapy, rabies-associated symptoms were atypical, and
      rabies was neglected because serum RABV-specific antibodies were negative. An
      unknown wound on the forehead of the donor was found 2 months before the onset of
      symptoms. Based on the clinical, epidemiological, and molecular findings, we
      speculated that the RABV initially originated in the donor from a dog bite, and
      was then transmitted to the recipients by organ transplantation. An uncertain
      exposure history and misdiagnosis played important roles in the spread of the
      RABV. Rabies should be considered in patients with acute progressive encephalitis
      of unexplained etiology, especially in potential organ donors.

PMID- 29637048
TI  - Leptospira interrogans Secreted Proteases Degrade Extracellular Matrix and Plasma
      Proteins From the Host.
AB  - Leptospires are highly motile spirochetes equipped with strategies for efficient
      invasion and dissemination within the host. Our group previously demonstrated
      that pathogenic leptospires secrete proteases capable of cleaving and
      inactivating key molecules of the complement system, allowing these bacteria to
      circumvent host's innate immune defense mechanisms. Given the successful
      dissemination of leptospires during infection, we wondered if such proteases
      would target a broader range of host molecules. In the present study, the
      proteolytic activity of secreted leptospiral proteases against a panel of
      extracellular matrix (ECM) and plasma proteins was assessed. The culture
      supernatant of the virulent L. interrogans serovar Kennewicki strain Fromm (LPF)
      degraded human fibrinogen, plasma fibronectin, gelatin, and the proteoglycans
      decorin, biglycan, and lumican. Interestingly, human plasminogen was not cleaved
      by proteases present in the supernatants. Proteolytic activity was inhibited by
      1,10-phenanthroline, suggesting the participation of metalloproteases. Moreover,
      production of proteases might be an important virulence determinant since culture
      attenuated or saprophytic Leptospira did not display proteolytic activity against
      ECM or plasma components. Exoproteomic analysis allowed the identification of
      three metalloproteases that could be involved in the degradation of host
      components. The ability to cleave conjunctive tissue molecules and coagulation
      cascade proteins may certainly contribute to invasion and tissue destruction
      observed upon infection with Leptospira.

PMID- 29637051
TI  - Coping with Stress among Pregnant Women with Gestational Diabetes Mellitus.
AB  - Introduction: The stress of pregnancy itself, gestational diabetes mellitus (GDM)
      that develops during pregnancy is also a stressor, because it can cause serious
      maternal and fetal health problems. The aim of this study was to examine the
      relationships between the characteristics of pregnant women with GDM and their
      styles of coping with stress. Methods: This descriptive cross-sectional study was
      conducted on 126 pregnant women with GDM. The sample consisted of patients who
      applied to the diabetes mellitus training polyclinic of a training and research
      and university hospital in southeastern Turkey, Data were evaluated using
      descriptive statistics, Kolmogorov-Smirnov normality tests, Spearman's rho and
      Pearson Correlation analysis, the Student's t-test, Mann-Whitney U-test and
      Kruskal-Wallis- test by SPSS software (version 13.0). Results: It was determined
      that a planned pregnancy, a high educational level, a first pregnancy and weight
      gain were important factors in the women with GDM in the study who coped
      effectively with stress during pregnancy. Unemployment and a second or subsequent
      pregnancy were important factors in the women with GDM< who coped ineffectively
      with stress during pregnancy. In addition, it was determined that the hemoglobin
      HbA1c levels of the pregnant women with GDM with "optimistic" and "submissive"
      approaches towards coping with stress were lower. Conclusion: It was determined
      that pregnant women with optimistic and submissive approaches towards coping with
      stress had lower HbA1c levels. It is suggested that randomized controlled studies
      be conducted to further determine the coping styles of patients with GDM.

PMID- 29637049
TI  - Mycobacterium tuberculosis GrpE, A Heat-Shock Stress Responsive Chaperone,
      Promotes Th1-Biased T Cell Immune Response via TLR4-Mediated Activation of
      Dendritic Cells.
AB  - Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, is an
      extremely successful pathogen with multifactorial ability to control the host
      immune response. Insights into the Mtb factors modulating host response are
      required for the discovery of novel vaccine antigen targets as well as a better
      understanding of dynamic interactions between the bacterial factors and host
      cells. Here, we exploited the functional role of Mtb GrpE, a cofactor of heat
      shock protein 70 (HSP70), in promoting naive CD4+/CD8+T cell differentiation
      toward Th1-type T-cell immunity through interaction with dendritic cells (DCs).
      GrpE functionally induced DC maturation by up-regulating the expression of cell
      surface molecules (CD80, CD86, and MHC class I and II) and production of several
      pro-inflammatory cytokines (TNF-alpha, IL-1beta, IL-6, and IL-12p70) in DCs.
      These effects of GrpE in DC activation were initiated upon binding to Toll-like
      receptor 4 (TLR4) followed by activation of downstream MyD88-, TRIF-, MAPK-, and
      NF-kappaB-dependent signaling pathways. GrpE-activated DCs displayed an excellent
      capacity to effectively polarize naive CD4+ and CD8+ T cells toward Th1-type T
      cell immunity with the dose-dependent secretion of IFN-gamma and IL-2 together
      with increased levels of CXCR3 expression. Notably, GrpE-stimulated DCs induced
      the proliferation of GrpE-specific Th1-type effector/memory
      CD4+/CD8+CD44highCD62Llow T cells from the spleen of Mtb-infected mice in a TLR4
      dependent manner. Collectively, these results demonstrate that GrpE is a novel
      immune activator that interacts with DCs, in particular, via TLR4, to generate
      Th1-biased memory T cells in an antigen-specific manner. GrpE may contribute to
      the enhanced understanding of host-pathogen interactions as well as providing a
      rational basis for the discovery of new potential targets to develop an effective
      tuberculosis vaccine.

PMID- 29637050
TI  - Using Social Cognitive Theory to Predict Medication Compliance Behavior in
      Patients with Depression in Southern United States in 2016 in a Cross-Sectional
      Study.
AB  - Introduction: Depression is a major public health issue. One of the concerns in
      depression research and practice pertains to non-compliance to prescribed
      medications. The purpose of the study was to predict compliance with medication
      use for patients with depression using social cognitive theory (SCT). Based on
      this study it was envisaged that recommendations for interventions to enhance
      compliance for medication use could be developed for patients with depression.
      Methods: The study was conducted using cross sectional design (n=148) in southern
      United States with a convenience sample of clinic-based depression patients with
      a 37-item valid and reliable questionnaire. Sample size was calculated to be 148
      using G*Power (five predictors with a 0.80 power at the 0.05 alpha level and an
      estimated effect size of 0.10 with an inflation by 10% for missing data). Social
      cognitive theory constructs of expectations, self-efficacy and self-efficacy in
      overcoming barriers, self-control, and environment were reified. Data were
      analyzed using multiple linear regression and multiple logistic regression
      analyses. Results: Self-control for taking medication for depression (P=0.04),
      expectations for taking medication for depression (P=0.025), age (P<0.0001) and
      race (P=0.04) were significantly related to intent for taking medication for
      depression (Adjusted R2 = 0.183). In race, Blacks had lower intent to take
      medication for depression. Conclusion: Social cognitive theory is weakly
      predictive with low explained variance for taking medication for depression. It
      needs to be bolstered by newer theories like integrative model or multi-theory
      model of health behavior change for designing educational interventions aimed at
      enhancing compliance to medication for depression.

PMID- 29637052
TI  - Dietary and Fluid Regime Adherence in Chronic Kidney Disease Patients.
AB  - Introduction: Patients with Chronic Kidney Disease (CKD) needs to modify their
      lifestyle chiefly focusing on diet and fluid intake as the prognosis of these
      patients largely depends on adherence to the recommended nutritional regime. Non
      adherence to the suggested diet and fluids regime leads to rapid worsening of the
      condition. Methods: Cross sectional survey was conducted to determine the level
      of adherence to the dietary and fluids restriction among CKD patients. Inclusion
      criteria's was, age between 18- 65 years, patients with CKD for at least 6 months
      and received dietary counseling. Consecutive sampling technique was used to
      select 100 patients. Data was collected with self-reported Dialysis Diet and
      Fluid non adherence Questionnaire (DDFQ). Results: Majority (73%) of the subjects
      was males, 64% belongs to 40-60 years age, majority of them were unemployed. Mean
      Body Mass Index (BMI) was 20.52 kg/m2, the mean duration of the treatment is 2.15
      years and mean fluid intake was 2153ml ml/day and inter-dialytic weight gain was
      1.48 kg. Regarding adherence, 20% of them had mild deviation and 69% of them had
      moderate deviation from dietary restrictions and similarly 69 % of the
      participants had moderate deviation, and 22% of them had mild deviation from
      fluid restriction guidelines. Low level of adherence to fluid and diet
      restrictions was noted in illiterate patients which was significant P<0.05.
      Conclusion: In spite of the dietary counseling, considerable proportions of the
      patients were non adherent to the diet and fluid restrictions which necessitate
      regular counseling to patient and family members.

PMID- 29637053
TI  - The Effect of Two-Staged Warm Compress on the Pain Duration of First and Second
      Labor Stages and Apgar Score in Prim Gravida Women: a Randomized Clinical Trial.
AB  - Introduction: The aim of this study was to assess the effect of two-stage warm
      compress technique on the pain duration of the first and second labor stages and
      neonatal outcomes. Methods: The clinical trial was done on 150 women (75 subjects
      in each groups) in Shiraz-affiliated hospitals in 2012 A two-staged warm compress
      was done for 15-20 minutes in the first and second labor phase (cervical
      dilatation of 7 and 10 cm with zero status) while the control group received
      hospital routine care. The duration of labor and Apgar score were evaluated.
      Results: According to t-test, the average of labor duration was lower in the
      intervention group compared to the control group at the second stage. However,
      there was no significant difference for labor duration at the first stage and the
      first and fifth minute Apgar score. Conclusion: According to the result, this
      intervention seems a good method for decreasing labor duration at the second
      stage of parturition.

PMID- 29637054
TI  - Concerns of Parents with or Raising Adolescent Children: a Qualitative Study of
      Iranian Families.
AB  - Introduction: Adolescence is a challenging period and cultural background plays
      an important role in families with adolescent. So exploring parents' concerns in
      the specific context of Iran may improves nurses' family-based services and helps
      to reduce conflicts Iranian families with respect to adolescents. In this paper
      we explore perceptions of Iranian parents' concerns in the family with raising
      adolescent children. Methods: Participants of this qualitative content analysis
      study were 23 parents with adolescents, who were recruited through purposive
      sampling. Data collection was done through semi structured in-depth interviews
      and analyzed based on Graneheim and Landman's approach. Lincoln and Guba's
      criteria were used to ensure the accuracy and strength of the study. Results: The
      theme "rebellion against parents' authority" was supported by two categories: (1)
      parent-teenage conflict, and (2) difficulty in controlling. As the offspring
      enter adolescence, parents feel that their child is going to leave their domain.
      Conclusion: Findings from this study showed that the incongruity arises when
      traditional family norms fail to adapt to new patterns. Change of social and
      cultural norms in developing societies, has led to generational differences in
      families. This issue accompanied with adolescence, increases parents' concern. So
      we recommend parental educational programs for learning effectively patterns for
      resisting internal challenges and communicate with adolescents.

PMID- 29637055
TI  - Features of Coping with Disease in Iranian Multiple Sclerosis Patients: a
      Qualitative Study.
AB  - Introduction: Coping with disease is of the main components improving the quality
      of life in multiple sclerosis patients. Identifying the characteristics of this
      concept is based on the experiences of patients. Using qualitative research is
      essential to improve the quality of life. This study was conducted to explore the
      features of coping with the disease in patients with multiple sclerosis. Method:
      In this conventional content analysis study, eleven multiple sclerosis patients
      from Iran MS Society in Tehran (Iran) participated. Purposive sampling was used
      to select participants. Data were gathered using semi structured interviews. To
      analyze data, a conventional content analysis approach was used to identify
      meaning units and to make codes and categories. Results: Results showed that
      features of coping with disease in multiple sclerosis patients consists of (a)
      accepting the current situation, (b) maintenance and development of human
      interactions, (c) self-regulation and (d) self-efficacy. Each of these categories
      is composed of sub-categories and codes that showed the perception and experience
      of patients about the coping with disease. Conclusion: Accordingly, a unique set
      of features regarding features of coping with the disease were identified among
      the patients with multiple sclerosis. Therefore, working to ensure the emergence
      of, and subsequent reinforcement of these features in MS patients can be an
      important step in improving the adjustment and quality of their lives.

PMID- 29637056
TI  - Nurses' Lived Experience of Working with Nursing Students in Clinical Wards: a
      Phenomenological Study.
AB  - Introduction: Despite being aware of the importance of nurses' role in providing
      clinical training to nursing students, studies show that sufficient research has
      not yet been conducted on the experience of clinical nurses who are engaged in
      training nursing students outside their normal working hours. The present study
      aim to describe the experience of these nurses who are training outside their
      routine working hours. Methods: This study was conducted using descriptive
      phenomenology method. Twelve nurses was participated in this research. Data were
      collected using purposive sampling method and face to face interviews based on
      nurses' real life experience of students' learning in clinical settings through
      answering open-ended questions. Spiegel burg analysis method was used to analyze
      the data. Results: The result of data analysis was the derivation of four themes
      and eight sub-themes. Themes included "nurses as teaching sources", "changes in
      the balance of doing routine tasks", "professional enthusiasm", and "nurses as
      students' professional socialization source of inspiration". Sub-themes included
      "efficient education", "poor education", "support", "interference in the role,"
      "self-efficacy development", "inner satisfaction", "positive imaging" and "being
      a model". Conclusion: It is necessary that academic centers plan for teaching
      nurses working on a contractual basis in the field of the evaluation method and
      various methods of teaching. The findings also suggested the development of
      individual self-efficacy in clinical nurses who train students.

PMID- 29637057
TI  - Examining Social Health and Its Related Factors among Iranian Medical students.
AB  - Introduction: Given the importance of providing social health for students, this
      study was conducted to investigate the social health and its related factors
      among Iranian students of medical sciences. Methods: This descriptive and cross
      sectional study was carried out in 2016. The population of the study included
      students of Mazandaran University of Medical Sciences (Sari, Iran). Using random
      sampling, we selected 352 students. Eligible students for the study were those
      who (i) consented to participate, (ii) agreed to participate fully, and (iii) had
      no physical illnesses. Exclusion from the study was due to any event that
      prevented them from participating in the study (e.g., the death of a family
      member). Then, standardized questionnaire of "Keyes's Social Well-being" and
      demographic questionnaire were used in this study to collect data. The data were
      tabulated and analyzed by means of SPSS 13.0 for Windows (SPSS Inc., Chicago, IL,
      USA), which was used to calculate descriptive and inferential (Two-way ANOVA)
      indices. Results: In this study, 202 women and 150 men participated with the mean
      age of 23.14 (2.41). The mean score of social health of students was average
      92.99 (7.54). About 75.4% of participants had average levels of social health.
      Maximum and minimum levels of social health were related to contribution 20.64
      (3.65) and social coherence 15.86 (2.12) respectively. There were no differences
      in the overall social health score of the students in terms of gender; however,
      regarding marital status, place of residence, father's education, and mother's
      education, there was a significant difference among students. Conclusion: Given
      the importance of social health, it is necessary to have proper planning such as
      providing for the requirements of stable marriages for students, good place of
      residence to improve the quality of life and enhance their satisfaction with it.

PMID- 29637058
TI  - Lethal Area 50 in Patients with Burn Injuries in North West, Iran.
AB  - Introduction: In view of their considerably high rates of mortality and
      morbidity, burns are still viewed as one of the most important health-threatening
      environmental hazards imposing a significant burden on the health care system in
      low and middle-income countries. This study seeks to determine the lethal area
      fifty percent (LA50) in all burn patients admitted over a period of five years
      and the factors influencing mortality in burn injuries. Methods: This study was a
      cross-sectional carried out from 2010 to 2014 in Sina Hospital of Tabriz, 1226
      participant including 319 women, 346 men, 272 girls, and 289 boys were selected
      through stratified sampling. The demographic and clinical data of patients (
      their age, gender, burn type, TBSA, the season and consequences of burning) were
      all extracted and then analyzed, using descriptive statistics (measures of
      central tendency and variability) and inferential statistics(chi-square and
      linear regression)at a significance level of 0.05. The LA50 was calculated
      through determining the relationship between the total body surface area and
      mortality rate (The extent of the body burns measured and recorded based on Lando
      Chart in hospitals). Results: The highest (47.6%) and the lowest (3.8%) rates of
      burns were observed among those aged below 16 and above 65, respectively. The
      majority of the participants were residents of cities (55.4%), married (34.6%),
      illiterate (56.6%), and housewives (14.8%). Most burns were caused by accidents
      (98.4%) at home (90.6%). Most patients had suffered first- and second-degree
      burns (68.4%), with no inhalation damages (99.5%). Hot liquids were the main
      culprit in most of the burns (58.7%) and the upper extremities were the most
      frequently affected areas (34.8%). There was .99 rise in mortality for every
      percent increase in TBSA, and there seemed to be a significant relationship
      between the age level and the eventual outcome- the higher the age, the more
      likely for the incident to end in death.LA50 was also determined 43.73 percent
      for five years. Finally, the study findings showed that female gender, TBSA and
      age are associated with death from burn. Conclusion: Given the high LA50 index at
      this center, it is of high priority in our country to enhance the public
      knowledge and the quality of the care provided for the burn patients. Patients at
      risk including women, children, elderly and extensive burns should be considered.

PMID- 29637059
TI  - The importance of imaging strategies for pre-clinical and clinical in vivo
      distribution of oncolytic viruses.
AB  - Oncolytic viruses (OVs) are an emergent and unique therapy for cancer patients.
      Similar to chemo- and radiation therapy, OV can lyse (kill) cancer cell directly.
      In general, the advantages of OVs over other treatments are primarily: a higher
      safety profile (as shown by less adverse effects), ability to replicate,
      transgene(s) delivery, and stimulation of a host's immune system against cancer.
      The latter has prompted successful use of OVs with other immunotherapeutic
      strategies in a synergistic manner. In spite of extended testing in pre-clinical
      and clinical setting, using biologically derived therapeutics like virus always
      raises potential concerns about safety (replication at non-intended locations)
      and bio-availability of the product. Recent advent in in vivo imaging techniques
      dramatically improves the convenience of use, quality of pictures, and amount of
      information acquired. Easy assessing of safety/localization of the
      biotherapeutics like OVs became a new potential weapon in the physician's arsenal
      to improve treatment outcome. Given that OVs are typically replicating, in vivo
      imaging can also track virus replication and persistence as well as precisely
      mapping tumor tissues presence. This review discusses the importance of imaging
      in vivo in evaluating OV efficacy, as well as currently available tools and
      techniques.

PMID- 29637060
TI  - Reconstruction of large oroantral defects using a pedicled buccal fat pad.
AB  - Background: Oroantral communicating defects, characterized by a connection
      between the maxillary sinus and the oral cavity, are often induced by tooth
      extraction, removal of cysts and benign tumors, and resection of malignant
      tumors. The surgical defect may develop into an oroantral fistula, with resultant
      patient discomfort and chronic maxillary sinusitis. Small defects may close
      spontaneously; however, large oroantral defects generally require reconstruction.
      These large defects can be reconstructed with skin grafts and vascularized free
      flaps with or without bone graft. However, such surgical techniques are complex
      and technically difficult. A buccal fat pad is an effective, reliable, and
      straightforward material for reconstruction. Case presentation: This report
      describes three cases of reconstruction of large oroantral defects, all of which
      were covered by a pedicled buccal fat pad. Follow-up photography and radiologic
      imaging showed successful closure of the oroantral defects. Furthermore, there
      were no operative site complications, and no patient reported postsurgical
      discomfort. Conclusion: In conclusion, the use of the pedicled buccal fat pad is
      a reliable, safe, and successful method for the reconstruction of large oroantral
      defects.

PMID- 29637061
TI  - Considerations for Assessing the Appropriateness of High-Cost Pediatric Care in
      Low-Income Regions.
AB  - It may be difficult to predict the consequences of provision of high-cost
      pediatric care (HCC) in low- and middle-income countries (LMICs), and these
      consequences may be different to those experienced in high-income countries. An
      evaluation of the implications of HCC in LMICs must incorporate considerations of
      the specific context in that country (population age profile, profile of disease,
      resources available), likely costs of the HCC, likely benefits that can be gained
      versus the costs that will be incurred. Ideally, the process that is followed in
      decision making around HCC should be transparent and should involve the
      communities that will be most affected by those decisions. It is essential that
      the impacts of provision of HCC are carefully monitored so that informed
      decisions can be made about future provision medical interventions.

PMID- 29637063
TI  - Control of Cattle Ticks and Tick-Borne Diseases by Acaricide in Southern Province
      of Zambia: A Retrospective Evaluation of Animal Health Measures According to
      Current One Health Concepts.
AB  - One health thinking for health interventions is increasingly being used to
      capture previously unseen stakeholders and impacts across people, animals, and
      the environment. The Network for One Health Evaluation (NEOH) proposes a systems
      based framework to quantitatively assess integration and highlight the added
      value (theory of change) that this approach will bring to a project. This case
      study will retrospectively evaluate the pioneering use of a One Health (OH)
      approach during an international collaboration (satellite project to tackle
      production losses due to tick-borne disease in cattle in Southern Zambia in late
      1980s). The objective of the evaluation is twofold: retrospective evaluation the
      OH-ness of the satellite project and identification of costs and benefits. Data
      for evaluation was recovered from publications, project documents, and witness
      interviews. A mixed qualitative and quantitative evaluation was undertaken. In
      this case study, a transdisciplinary approach allowed for the identification of a
      serious public health risk arising from the unexpected reuse of chemical
      containers by the local public against advice. Should this pioneering project not
      have been completed then it is assumed this behavior could have had a large
      impact on public wellbeing and ultimately reduced regional productivity and
      compromised welfare. From the economic evaluation, the costs of implementing this
      OH approach, helping to avoid harm, were small in comparison to overall project
      costs. The overall OH Index was 0.34. The satellite project demonstrated good OH
      operations by managing to incorporate the input across multiple dimensions but
      was slightly weaker on OH infrastructures (OH Ratio = 1.20). These quantitative
      results can be used in the initial validation and benchmarking of this novel
      framework. Limitations of the evaluation were mainly a lack of data due to the
      length of time since project completion and a lack of formal monitoring of
      program impact. In future health strategy development and execution, routine
      monitoring and evaluation from an OH perspective (by utilizing the framework
      proposed by NEOH), could prove valuable or used as a tool for retrospective
      evaluation of existing policies.

PMID- 29637062
TI  - Idiopathic Mast Cell Activation Syndrome With Associated Salicylate Intolerance.
AB  - Idiopathic mast cell activation syndrome can be a rare cause for chronic
      abdominal pain in children. It remains a diagnosis by exclusion that can be
      particularly challenging due to the vast variety of possible clinical
      manifestations. We present a 13-year-old boy who suffered from a multitude of
      unspecific complaints over a long period of time. In this case, an assessment of
      mast cell-derived metabolites and immunohistochemical analysis of bioptic
      specimen was worthwhile. After ruling out, primary (oncologic) and secondary
      causes for mast cell activation, pharmacologic treatment adapted to the patient's
      salicylate intolerance resulted in a major relief of symptoms.

PMID- 29637064
TI  - Perceived Obstacles Faced by Diabetes Patients Attending University of Gondar
      Hospital, Northwest Ethiopia.
AB  - Background: Diabetes mellitus (DM) is a non-communicable, chronic, and
      progressive disease that can lead to serious complications and even to premature
      death. A closer understanding of the DM patients' specific obstacles will provide
      a greater clarity of the factors influencing their disease-related quality of
      life and coping with daily life. The study aimed to evaluate the obstacles of DM
      patients attending ambulatory clinic of the University of Gondar Hospital (UOGH),
      Northwest Ethiopia. Methods: A cross-sectional study was conducted from February
      to April 2017 at ambulatory clinic of the UOGH. A validated short version of the
      diabetic obstacle questionnaire was used. The internal reliability of the
      questionnaire was checked using Cronbach's alpha and was found to be 92.5%. To
      determine any association between each of the nine sections of the questionnaire
      and age, sex, residence, educational status, and DM type, a binary logistic
      regression was performed. Results: The mean age of respondents was 38.69 +/-
      15.39 years. Compared with patients with type 1 DM, patients with type 2 DM
      reported poorer relationships with medical professionals (adjusted odds ratio
      (AOR): 2.191, p-value = 0.027) and less support from families and friends (AOR:
      1.913, p-value = 0.049). Patients coming from rural areas (AOR: 2.947, p = 0.002)
      and having no formal education (AOR: 2.078, p = 0.029) also received less support
      from families and friends. Conclusion: DM patients in UOGH reported several
      obstacles related to patients' relationship with health professionals, lack of
      support from their friends, lack of knowledge about DM, and lack of motivation to
      exercise. Effective efforts should be initiated to improve healthier environment
      to educate, care and preventive services for people with DM.

PMID- 29637065
TI  - Biosourced Polymetallic Catalysis: A Surprising and Efficient Means to Promote
      the Knoevenagel Condensation.
AB  - Zn hyperaccumulator (Arabidobsis halleri) and Zn accumulator Salix "Tordis"
      (Salix schwerinii * Salix viminalis) have shown their interest in the
      phytoextraction of polluted brownfields. Herein, we explore a novel methodology
      based on the chemical valorization of Zn-rich biomass produced by these
      metallophyte plants. The approach is based on the use of polymetallic salts
      derived from plants as bio-based catalysts in organic chemistry. The formed
      ecocatalysts were characterized via ICP-MS, X-ray diffraction (XRD), Fourier
      transform infrared spectroscopy (FT-IR) in order to precise the chemical
      composition, structure, and behavior of the formed materials. The Doebner
      Knoevenagel reaction was chosen as model reaction to study their synthetic
      potential. Significant differences to usual catalysts such as zinc (II) chloride
      are observed. They can principally be related to a mixture of unusual mineral
      species. DFT calculations were carried out on these salts in the context of the
      Gutmann theory. They allow the rationalization of experimental results. Finally,
      these new bio-based polymetallic catalysts illustrated the interest of this
      concept for green and sustainable catalysis.

PMID- 29637066
TI  - How Diverse Are the Protein-Bound Conformations of Small-Molecule Drugs and
      Cofactors?
AB  - Knowledge of the bioactive conformations of small molecules or the ability to
      predict them with theoretical methods is of key importance to the design of
      bioactive compounds such as drugs, agrochemicals, and cosmetics. Using an
      elaborate cheminformatics pipeline, which also evaluates the support of
      individual atom coordinates by the measured electron density, we compiled a
      complete set ("Sperrylite Dataset") of high-quality structures of protein-bound
      ligand conformations from the PDB. The Sperrylite Dataset consists of a total of
      10,936 high-quality structures of 4,548 unique ligands. Based on this dataset, we
      assessed the variability of the bioactive conformations of 91 small molecules
      each represented by a minimum of ten structures-and found it to be largely
      independent of the number of rotatable bonds. Sixty-nine molecules had at least
      two distinct conformations (defined by an RMSD greater than 1 A). For a
      representative subset of 17 approved drugs and cofactors we observed a clear
      trend for the formation of few clusters of highly similar conformers. Even for
      proteins that share a very low sequence identity, ligands were regularly found to
      adopt similar conformations. For cofactors, a clear trend for extended
      conformations was measured, although in few cases also coiled conformers were
      observed. The Sperrylite Dataset is available for download from
      http://www.zbh.uni-hamburg.de/sperrylite_dataset.

PMID- 29637067
TI  - Comprehensive Adsorption Studies of Doxycycline and Ciprofloxacin Antibiotics by
      Biochars Prepared at Different Temperatures.
AB  - This paper comparatively investigated the removal efficiency and mechanisms of
      rice straw biochars prepared under three pyrolytic temperatures for two kinds of
      tetracycline and quinolone antibiotics (doxycycline and ciprofloxacin). The
      influencing factors of antibiotic adsorption (including biochar dosage, pH,
      background electrolytes, humic acid, initial antibiotics concentration, contact
      time, and temperature) were comprehensively studied. The results suggest that
      biochars produced at high-temperature [i.e., 700 degrees C (BC700)], have higher
      adsorption capacity for the two antibiotics than low-temperature (i.e., 300-500
      degrees C) biochars (BC300 and BC500). Higher surface area gives rise to greater
      volume of micropores and mesopores, and higher graphitic surfaces of the BC700
      contributed to its higher functionality. The maximum adsorption capacity was
      found to be in the following order: DOX > CIP. The pi-pi EDA interaction and
      hydrogen bonding might be the predominant adsorption mechanisms. Findings in this
      study highlight the important roles of high-temperature biochars in controlling
      the contamination of tetracycline and quinolone antibiotics in the environment.

PMID- 29637068
TI  - Porous Nanocrystalline Silicon Supported Bimetallic Pd-Au Catalysts: Preparation,
      Characterization, and Direct Hydrogen Peroxide Synthesis.
AB  - Bimetallic Pd-Au catalysts were prepared on the porous nanocrystalline silicon
      (PSi) for the first time. The catalysts were tested in the reaction of direct
      hydrogen peroxide synthesis and characterized by standard structural and chemical
      techniques. It was shown that the Pd-Au/PSi catalyst prepared from conventional
      H2[PdCl4] and H[AuCl4] precursors contains monometallic Pd and a range of
      different Pd-Au alloy nanoparticles over the oxidized PSi surface. The PdAu2/PSi
      catalyst prepared from the [Pd(NH3)4][AuCl4]2 double complex salt (DCS) single
      source precursor predominantly contains bimetallic Pd-Au alloy nanoparticles. For
      both catalysts the surface of bimetallic nanoparticles is Pd-enriched and
      contains palladium in Pd0 and Pd2+ states. Among the catalysts studied, the
      PdAu2/PSi catalyst was the most active and selective in the direct H2O2 synthesis
      with H2O2 productivity of 0.5 [Formula: see text] at selectivity of 50% and H2O2
      concentration of 0.023 M in 0.03 M H2SO4-methanol solution after 5 h on stream at
      -10 degrees C and atmospheric pressure. This performance is due to high activity
      in the H2O2 synthesis reaction and low activities in the undesirable H2O2
      decomposition and hydrogenation reactions. Good performance of the PdAu2/PSi
      catalyst was associated with the major part of Pd in the catalyst being in the
      form of the bimetallic Pd-Au nanoparticles. Porous silicon was concluded to be a
      promising catalytic support for direct hydrogen peroxide synthesis due to its
      inertness with respect to undesirable side reactions, high thermal stability, and
      conductivity, possibility of safe operation at high temperatures and pressures
      and a well-established manufacturing process.

PMID- 29637070
TI  - Lack of Detection of Bt Sugarcane Cry1Ab and NptII DNA and Proteins in Sugarcane
      Processing Products Including Raw Sugar.
AB  - Brazil is the largest sugarcane producer and the main sugar exporter in the
      world. The industrial processes applied by Brazilian mills are very efficient in
      producing highly purified sugar and ethanol. Literature presents evidence of lack
      of DNA/protein in these products, regardless of the nature of sugarcane used as
      raw material. Recently CTNBio, the Brazilian biosafety authority, has approved
      the first biotechnology-derived sugarcane variety for cultivation, event CTC175
      A, which expresses the Cry1Ab protein to control the sugarcane borer (Diatraea
      saccharalis). The event also expresses neomycin-phosphotransferase type II
      (NptII) protein used as selectable marker during the transformation process.
      Because of the high purity of sugar and ethanol produced from genetically
      modified sugarcane, these end-products should potentially be classified as "pure
      substances, chemically defined," by Brazilian Biosafety Law No. 11.105. If this
      classification is to be adopted, these substances are not considered as "GMO
      derivatives" and fall out of the scope of Law No. 11.105. In order to assess
      sugar composition and quality, we evaluate Cry1Ab and NptII expression in several
      sugarcane tissues and in several fractions from laboratory-scale processing of
      event CTC175-A for the presence of these heterologous proteins as well as for the
      presence of traces of recombinant DNA. The results of these studies show that
      CTC175-A presents high expression of Cry1Ab in leaves and barely detectable
      expression of heterologous proteins in stalks. We also evaluated the presence of
      ribulose-1,5-bisphosphate carboxylase/oxygenase protein and DNA in the fractions
      of the industrial processing of conventional Brazilian sugarcane cultivars.
      Results from both laboratory and industrial processing were concordant,
      demonstrating that DNA and protein are not detected in the clarified juice and
      downstream processed fractions, including ethanol and raw sugar, indicating that
      protein and DNA are removed and/or degraded during processing. In conclusion, the
      processing of conventional sugarcane and CTC175-A Bt event results in downstream
      products with no detectable concentrations of heterologous DNA or new protein.
      These results help in the classification of sugar and ethanol derived from CTC175
      A event as pure, chemically defined substances in Brazil and may relieve
      regulatory burdens in countries that import Brazilian sugar.

PMID- 29637071
TI  - Correlation of mRNA Expression and Signal Variability in Chronic Intracortical
      Electrodes.
AB  - Objective: The goal for this research was to identify molecular mechanisms that
      explain animal-to-animal variability in chronic intracortical recordings.
      Approach: Microwire electrodes were implanted into Sprague Dawley rats at an
      acute (1 week) and a chronic (14 weeks) time point. Weekly recordings were
      conducted, and action potentials were evoked in the barrel cortex by deflecting
      the rat's whiskers. At 1 and 14 weeks, tissue was collected, and mRNA was
      extracted. mRNA expression was compared between 1 and 14 weeks using a high
      throughput multiplexed qRT-PCR. Pearson correlation coefficients were calculated
      between mRNA expression and signal-to-noise ratios at 14 weeks. Main results: At
      14 weeks, a positive correlation between signal-to-noise ratio (SNR) and NeuN and
      GFAP mRNA expression was observed, indicating a relationship between recording
      strength and neuronal population, as well as reactive astrocyte activity. The
      inflammatory state around the electrode interface was evaluated using M1-like and
      M2-like markers. Expression for both M1-like and M2-like mRNA markers remained
      steady from 1 to 14 weeks. Anti-inflammatory markers, CD206 and CD163, however,
      demonstrated a significant positive correlation with SNR quality at 14 weeks. VE
      cadherin, a marker for adherens junctions, and PDGFR-beta, a marker for
      pericytes, both partial representatives of blood-brain barrier health, had a
      positive correlation with SNR at 14 weeks. Endothelial adhesion markers revealed
      a significant increase in expression at 14 weeks, while CD45, a pan-leukocyte
      marker, significantly decreased at 14 weeks. No significant correlation was found
      for either the endothelial adhesion or pan-leukocyte markers. Significance: A
      positive correlation between anti-inflammatory and blood-brain barrier health
      mRNA markers with electrophysiological efficacy of implanted intracortical
      electrodes has been demonstrated. These data reveal potential mechanisms for
      further evaluation to determine potential target mechanisms to improve
      consistency of intracortical electrodes recordings and reduce animal-to
      animal/implant-to-implant variability.

PMID- 29637069
TI  - Targeting Channels and Transporters in Protozoan Parasite Infections.
AB  - Infectious diseases caused by pathogenic protozoa are among the most significant
      causes of death in humans. Therapeutic options are scarce and massively
      challenged by the emergence of resistant parasite strains. Many of the current
      anti-parasite drugs target soluble enzymes, generate unspecific oxidative stress,
      or act by an unresolved mechanism within the parasite. In recent years,
      collections of drug-like compounds derived from large-scale phenotypic
      screenings, such as the malaria or pathogen box, have been made available to
      researchers free of charge boosting the identification of novel promising
      targets. Remarkably, several of the compound hits have been found to inhibit
      membrane proteins at the periphery of the parasites, i.e., channels and
      transporters for ions and metabolites. In this review, we will focus on the
      progress made on targeting channels and transporters at different levels and the
      potential for use against infections with apicomplexan parasites mainly
      Plasmodium spp. (malaria) and Toxoplasma gondii (toxoplasmosis), with
      kinetoplastids Trypanosoma brucei (sleeping sickness), Trypanosoma cruzi (Chagas
      disease), and Leishmania ssp. (leishmaniasis), and the amoeba Entamoeba
      histolytica (amoebiasis).

PMID- 29637073
TI  - What Do We Know About Component Separation Techniques for Abdominal Wall Hernia
      Repair?
AB  - Introduction: The component separation technique (CST) was introduced to
      abdominal wall reconstruction to treat large, complex hernias. It is very
      difficult to compare the published findings because of the vast number of
      technical modifications to CST as well as the heterogeneity of the patient
      population operated on with this technique. Material and Methods: The main focus
      of the literature search conducted up to August 2017 in Medline and PubMed was on
      publications reporting comparative findings as well as on systematic reviews in
      order to formulate statements regarding the various CSTs. Results: CST without
      mesh should no longer be performed because of too high recurrence rates. Open
      anterior CST has too high a surgical site occurrence rate and henceforth should
      only be conducted as endoscopic and perforator sparing anterior CST. Open
      posterior CST and posterior CST with transversus abdominis release (TAR) produce
      better results than open anterior CST. To date, no significant differences have
      been found between endoscopic anterior, perforator sparing anterior CST and
      posterior CST with transversus abdominis release. Robot-assisted posterior CST
      with TAR is the latest, very promising alternative. The systematic use of
      biologic meshes cannot be recommended for CST. Conclusion: CST should always be
      performed with mesh as endoscopic or perforator sparing anterior or posterior
      CST. Robot-assisted posterior CST with TAR is the latest development.

PMID- 29637075
TI  - Accumulating physical activity in at least 10-minute bouts predicts better lung
      function after 3-years in adults with cystic fibrosis.
AB  - Achieving physical activity guidelines by undertaking multiple bouts of moderate
      vigorous physical activity >=10 min duration, but not shorter periods of
      activity, was independently associated with less decline in FEV1over 3 years
      among adults with CF http://ow.ly/yk6930ivCV8.

PMID- 29637074
TI  - Gaussian-Based Smooth Dielectric Function: A Surface-Free Approach for Modeling
      Macromolecular Binding in Solvents.
AB  - Conventional modeling techniques to model macromolecular solvation and its effect
      on binding in the framework of Poisson-Boltzmann based implicit solvent models
      make use of a geometrically defined surface to depict the separation of
      macromolecular interior (low dielectric constant) from the solvent phase (high
      dielectric constant). Though this simplification saves time and computational
      resources without significantly compromising the accuracy of free energy
      calculations, it bypasses some of the key physio-chemical properties of the
      solute-solvent interface, e.g., the altered flexibility of water molecules and
      that of side chains at the interface, which results in dielectric properties
      different from both bulk water and macromolecular interior, respectively. Here we
      present a Gaussian-based smooth dielectric model, an inhomogeneous dielectric
      distribution model that mimics the effect of macromolecular flexibility and
      captures the altered properties of surface bound water molecules. Thus, the model
      delivers a smooth transition of dielectric properties from the macromolecular
      interior to the solvent phase, eliminating any unphysical surface separating the
      two phases. Using various examples of macromolecular binding, we demonstrate its
      utility and illustrate the comparison with the conventional 2-dielectric model.
      We also showcase some additional abilities of this model, viz. to account for the
      effect of electrolytes in the solution and to render the distribution profile of
      water across a lipid membrane.

PMID- 29637076
TI  - Outcome of advanced lung cancer with central airway obstruction versus without
      central airway obstruction.
AB  - Patients with central airway obstruction (CAO) from advanced lung cancer present
      with significant morbidity and are assumed to have lower survival. Hence, they
      are offered only palliative support. We asked if patients who have advanced lung
      cancer with CAO (recanalised and treated) will behave similarly to those with
      advanced lung cancer without CAO. This study was a retrospective review of the
      medical records of the patients managed for advanced lung cancer during 2010 and
      2015 at our institution. 85 patients were studied. Median survival and 1-, 2- and
      5-year survival were 5.8 months, 30.3%, 11.7% and 2.3% versus 9.3 months, 35.7%,
      9.6% and 4.7%, respectively, in the CAO and no CAO groups (p=0.30). More patients
      presented with respiratory failure (15 (35%) versus none; p=0.0001) and required
      assisted mechanical ventilation (10 (23.3%) versus none; p=0.001) in the CAO
      group compared with the no CAO group. Fewer patients received chemotherapy in the
      CAO group (11 (25.5%)) compared with the no CAO group (23 (54.7%); p=0.008).
      There was no difference in survival among patients with advanced lung cancer
      whether they presented with CAO or without CAO. Survival was similar to those
      without CAO in patients with recanalised CAO despite greater morbidity and lesser
      use of chemotherapy, strongly advocating bronchoscopic recanalisation of CAO.
      These findings dispel the nihilism associated with such cases.

PMID- 29637077
TI  - Mask pressure effects on the nasal bridge during short-term noninvasive
      ventilation.
AB  - The aim of this study was to assess the influence of different masks, ventilator
      settings and body positions on the pressure exerted on the nasal bridge by the
      mask and subjective comfort during noninvasive ventilation (NIV). We measured the
      pressure over the nasal bridge in 20 healthy participants receiving NIV via four
      different NIV masks (three oronasal masks, one nasal mask) at three different
      ventilator settings and in the seated or supine position. Objective pressure
      measurements were obtained with an I-Scan pressure-mapping system. Subjective
      comfort of the mask fit was assessed with a visual analogue scale. The masks
      exerted mean pressures between 47.6+/-29 mmHg and 91.9+/-42.4 mmHg on the nasal
      bridge. In the supine position, the pressure was lower in all masks (57.1+/-31.9
      mmHg supine, 63.9+/-37.3 mmHg seated; p<0.001). With oronasal masks, a change of
      inspiratory positive airway pressure (IPAP) did not influence the objective
      pressure over the nasal bridge. Subjective discomfort was associated with higher
      IPAP and positively correlated with the pressure on the skin. Objective
      measurement of pressure on the skin during mask fitting might be helpful for mask
      selection. Mask fitting in the supine position should be considered in the
      clinical routine.

PMID- 29637072
TI  - A Lexicon of DNA Modifications: Their Roles in Embryo Development and the
      Germline.
AB  - 5-methylcytosine (5mC) on CpG dinucleotides has been viewed as the major
      epigenetic modification in eukaryotes for a long time. Apart from 5mC, additional
      DNA modifications have been discovered in eukaryotic genomes. Many of these
      modifications are thought to be solely associated with DNA damage. However,
      growing evidence indicates that some base modifications, namely 5
      hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), 5-carboxylcytosine (5caC),
      and N6-methadenine (6mA), may be of biological relevance, particularly during
      early stages of embryo development. Although abundance of these DNA modifications
      in eukaryotic genomes can be low, there are suggestions that they cooperate with
      other epigenetic markers to affect DNA-protein interactions, gene expression,
      defense of genome stability and epigenetic inheritance. Little is still known
      about their distribution in different tissues and their functions during key
      stages of the animal lifecycle. This review discusses current knowledge and
      future perspectives of these novel DNA modifications in the mammalian genome with
      a focus on their dynamic distribution during early embryonic development and
      their potential function in epigenetic inheritance through the germ line.

PMID- 29637079
TI  - Immunogenicity and safety of subunit influenza vaccines in pregnant women.
AB  - Pregnancy is a condition of modulated immune suppression, so this group of
      patients has increased risk of infectious diseases. Trivalent subunit vaccines,
      unadjusted Agrippal S1 (group I) and immunoadjuvant Grippol Plus (group II),
      containing 5 MUg of actual influenza virus strains, were administered
      respectively to 37 and 42 women in the second and third trimester of
      physiological pregnancy. The administration of subunit influenza vaccines was
      accompanied by the development of local reactions in no more than 10% of
      patients, compared with 4.9% of the 41 pregnant women in the placebo group (group
      III). Systemic reactions were of a general somatic nature, did not differ between
      vaccinated and placebo groups, and were not associated with vaccination.
      Physiological births in groups I, II and III were 94.6%, 92.9% and 85.4%,
      respectively, and the birth rates of children without pathologies were 91.9%,
      90.5% and 80.5%, respectively, and were comparable between groups. Vaccination
      stimulated the production of protective antibodies against influenza virus
      strains in 64.8-94.5% of patients after immunisation with an unadjusted vaccine
      and in 72.5-90.0% of patients after the administration of an immunoadjuvant
      vaccine. After 9 months, antibody levels were recorded in 51.3-72.9% in group I
      and 54.2-74.2% in group II. Immunisation against influenza in pregnant women
      provided a high level of seroprotection and seroconversion. Nevertheless, the
      level of seroprotection against the influenza strain A(H3N2, Victoria) was
      slightly lower in the group immunised with an unadjusted vaccine compared to
      those vaccinated with the immunoadjuvant vaccine.

PMID- 29637078
TI  - Noninvasive ventilation in stable hypercapnic COPD: what is the evidence?
AB  - Long-term noninvasive ventilation (NIV) to treat chronic hypercapnic respiratory
      failure is still controversial in severe chronic obstructive pulmonary disease
      (COPD) patients. However, with the introduction of high-intensity NIV, important
      benefits from this therapy have also been shown in COPD. In this review, the
      focus will be on the arguments for long-term NIV at home in patients with COPD.
      The rise of (high-intensity) NIV in COPD and the randomised controlled trials
      showing positive effects with this mode of ventilation will be discussed.
      Finally, the challenges that might be encountered (both in clinical practice and
      in research) in further optimising this therapy, monitoring and following
      patients, and selecting the patients who might benefit most will be reviewed.

PMID- 29637080
TI  - Risk of tuberculosis transmission among healthcare workers.
AB  - Data from a prospective molecular-epidemiological study (1997-2015) of patients
      with culture-confirmed tuberculosis in Hamburg, Germany, were evaluated to assess
      the occupational risk of Mycobacterium tuberculosis complex transmission in a low
      incidence setting. Isolates of M. tuberculosis complex were genotyped using
      IS6110 restriction fragment length polymorphism analysis. Results of structured
      questionnaires, geographical mapping and additional patient interviews were used
      for confirming epidemiological links. Out of the 2393 cases, 918 (38.4%) were
      classified into 224 clusters comprising 2-70 patients per cluster. Among the 918
      cluster members, epidemiological links could be confirmed in 340 (37.0%)
      patients. In total, 55 (2.3%) patients were healthcare workers; 26 healthcare
      workers remained unclustered, but 29 healthcare workers belonged to cluster
      groups. Conventional contact tracing performed before genotyping to identify
      sources of the reported index cases detected only 73 (3.1%) patients. Logistic
      regression analysis confirmed work in the healthcare sector as strongest
      predictor for clustering of patients with verified epidemiological links (odds
      ratio (OR) 3.1, 95% CI 1.6-5.9), followed by alcoholism (OR 2.3, 95% CI 1.7-3.2)
      and sputum smear positivity (OR 1.8, 95% CI 1.4-2.3). Immigrants were more likely
      to be cluster nonmembers (OR 0.3, 95% CI 0.3-0.5). Recent transmission in Hamburg
      within the 19-year study period was found to be strongly associated with working
      in a healthcare facility. Although clusters also include many "imported" strains
      from abroad or regional highly prevalent M. tuberculosis strains with no evident
      epidemiological connection, routine molecular-epidemiological survey is
      indispensable to optimising and controlling the effectiveness of TB control
      strategies in German healthcare settings.

PMID- 29637081
TI  - Mental health history-a contributing factor for poorer outcomes in burn
      survivors.
AB  - Background: A pre-morbid mental health history is common in patients with severe
      burn injuries. This creates challenges in providing rehabilitation. The aim of
      this study is to cross examine the possible impact of psychological co
      morbidities on outcomes. Methods: A notes audit was carried out examining
      patients that were admitted to Concord Hospital Burns Unit in a 3-year period
      (2010-2012). Patients with total body surface area (TBSA) of 20% or greater and
      aged between 16 and 50 years were included. Subjects were divided into a mental
      health group and a control group. SPSS version 21 statistic program was used for
      analysis the data. Results: Data collected included length of stay, time to
      achieve independence, %TBSA, types of burns and surgery required. Results of 69
      files showed that the average length of stay per %TBSA was nearly double in the
      patients with a mental health problem (1.47 vs 0.88). They also had a higher rate
      of re-graft (52% vs 22%) due to infection and poor nutrition. The average time
      for patients to achieve independence in daily living activity was significantly
      higher (p = 0.046) in the mental health group (36.2 days) versus the control
      group (24.1 days). Conclusion: Patients with a mental health history may have
      poorer general health. This may result in a higher failure rate of grafting,
      leading to a requirement of re-graft. Hence, it took a longer time to achieve
      independence, as well as a longer hospital stay. A mental health history in burn
      survivors can be a contributing factor for poorer outcomes in the adult
      population.

PMID- 29637082
TI  - Quantitative Anatomic Analysis of the Medial Ulnar Collateral Ligament Complex of
      the Elbow.
AB  - Background: A more detailed assessment of the anatomy of the entire medial ulnar
      collateral ligament complex (MUCLC) is desired as the rate of medial elbow
      reconstruction surgery continues to rise. Purpose: To quantify the anatomy of the
      MUCLC, including the anterior bundle (AB), posterior bundle (PB), and transverse
      ligament (TL). Study Design: Descriptive laboratory study. Methods: Ten unpaired,
      fresh-frozen cadaveric elbows underwent 3-dimensional (3D) digitization and
      computed tomography with 3D reconstruction. Ligament footprint areas and
      geometries, distances to key bony landmarks, and isometry were determined. A
      surgeon digitized the visual center of each footprint, and this location was
      compared with the geometric centroid calculated from the outline of the digitized
      footprint. Results: The mean surface area of the AB was 324.2 mm2, with an origin
      footprint of 32.3 mm2 and an elongated insertional footprint of 187.6 mm2
      (length, 29.7 mm). The mean area of the PB was 116.6 mm2 (origin, 25.9 mm2;
      insertion, 15.8 mm2), and the mean surface area of the TL was 134.5 mm2 (origin,
      21.2 mm2; insertion, 16.7 mm2). The geometric centroids of all footprints could
      be predicted within 0.8 to 1.3 mm, with the exception of the AB insertion
      centroid, which was 7.6 mm distal to the perceived center at the apex of the
      sublime tubercle. While the PB remained relatively isometric from 0 degrees  to
      90 degrees  of flexion (P = .606), the AB lengthened by 2.2 mm (P < .001).
      Conclusion: Contrary to several historical reports, the insertional footprint of
      the AB was larger, elongated, and tapered. The TL demonstrated a previously
      unrecognized expansive soft tissue insertion directly onto the AB, and additional
      analysis of the biomechanical contribution of this structure is needed. Clinical
      Relevance: These findings may serve as a foundation for future study of the MUCLC
      and help refine current surgical reconstruction techniques.

PMID- 29637084
TI  - Medicaid Health Insurance Status Limits Patient Accessibility to Rehabilitation
      Services Following ACL Reconstruction Surgery.
AB  - Background: In the senior author's (X.L.) orthopaedic sports medicine clinic in
      the United States (US), patients appear to have difficulty finding physical
      therapy (PT) practices that accept Medicaid insurance for postoperative
      rehabilitation. Purpose: To determine access to PT services for privately insured
      patients versus those with Medicaid who underwent anterior cruciate ligament
      (ACL) reconstruction in the largest metropolitan area in the state of
      Massachusetts, which underwent Medicaid expansion as part of the Affordable Care
      Act. Study Design: Cross-sectional study. Methods: Locations offering PT services
      were identified through Google, Yelp, and Yellow Pages internet searches. Each
      practice was contacted and queried about health insurance type accepted (Medicaid
      [public] vs Blue Cross Blue Shield [private]) for postoperative ACL
      reconstruction rehabilitation. Additional data collection points included time to
      first appointment, reason for not accepting insurance, and ability to refer to a
      location accepting insurance type. Median income and percentage of households
      living in poverty were also noted through US Census data for the town in which
      the practice was located. Results: Of the 157 PT locations identified, contact
      was made with 139 to achieve a response rate of 88.5%. Overall, 96.4% of
      practices took private insurance, while 51.8% accepted Medicaid. Among those
      locations that did not accept Medicaid, only 29% were able to refer to a clinic
      that would accept it. "No contract" was the most common reason why Medicaid was
      not accepted (39.4%). Average time to first appointment was 5.8 days for
      privately insured patients versus 8.4 days for Medicaid patients (P = .0001).
      There was no significant difference between clinic location (town median income
      or poverty level) and insurance type accepted. Conclusion: The study results
      reveal that 43% fewer PT clinics accept Medicaid as compared with private
      insurance for postoperative ACL reconstruction rehabilitation in a large
      metropolitan area. Furthermore, Medicaid patients must wait significantly longer
      for an initial appointment. Access to PT care is still limited despite the
      expansion of Medicaid insurance coverage to all patients in the state.

PMID- 29637083
TI  - Osseous Vascularity of the Medial Elbow After Ulnar Collateral Ligament
      Reconstruction: A Comparison of the Docking and Modified Jobe Techniques.
AB  - Background: Although vascularity plays a critical role in healing after ulnar
      collateral ligament (UCL) reconstruction, intraosseous blood flow to the medial
      epicondyle (ME) and sublime tubercle remains undefined. Purpose: To quantify
      vascular disruption caused by tunnel drilling with the modified Jobe and docking
      techniques for UCL reconstruction. Study Design: Controlled laboratory study.
      Methods: Eight matched pairs (16 specimens) of fresh-frozen cadaveric upper
      extremities were randomized to 1 of 2 study groups: docking technique or modified
      Jobe technique. One elbow in each pair underwent tunnel drilling by the assigned
      technique, while the contralateral elbow served as a control. Pregadolinium and
      postgadolinium magnetic resonance imaging were performed to quantify intraosseous
      vascularity within the ME, trochlea, and proximal ulna. Three-dimensional
      computed tomography (CT) and gross dissection were performed to assess terminal
      vessel integrity. Results: Ulnar tunnel drilling had minimal impact on
      vascularity of the proximal ulna, with maintenance of >95% blood flow for each
      technique. Perfusion in the ME was reduced 14% (to 86% of baseline) for the
      docking technique and 60% (to 40% of baseline) for the modified Jobe technique
      (mean difference, 46%; P = .029). Three-dimensional CT and gross dissection
      revealed increased disruption of small perforating vessels of the posterior
      aspect of the ME for the modified Jobe technique. Conclusion: Although tunnel
      drilling in the sublime tubercle appears to have a minimal effect on intraosseous
      vascularity of the proximal ulna, both the docking and modified Jobe techniques
      reduce flow in the ME. This reduction was 4 times greater for the modified Jobe
      technique, and these findings have important implications for UCL reconstruction
      surgery. Clinical Relevance: As the rate of revision UCL reconstructions
      continues to rise, investigation into causes for failure of primary surgery is
      needed. One potential cause is poor tendon-to-bone healing due to inadequate
      vascularity. This study quantifies the amount of vascular insult that is incurred
      in the ME during UCL reconstruction. While vascular insult is only one of many
      factors that affects the surgical success rate, surgeons performing this
      procedure should be mindful of this potential for vascular disruption.

PMID- 29637085
TI  - Clinical Outcomes and Return to Sport After Arthroscopic Anterior, Posterior, and
      Combined Shoulder Stabilization.
AB  - Background: Glenohumeral instability is a common abnormality, especially among
      athletes. Previous studies have evaluated outcomes after arthroscopic
      stabilization in patients with anterior or posterior shoulder instability but
      have not compared outcomes between groups. Purpose: To compare return-to-sport
      and other patient-reported outcomes in patients after primary arthroscopic
      anterior, posterior, and combined anterior and posterior shoulder stabilization.
      Study Design: Cohort study; Level of evidence, 3. Methods: Patients who underwent
      primary arthroscopic anterior, posterior, or combined anterior and posterior
      shoulder stabilization were contacted at a minimum 2-year follow-up. Patients
      completed a survey that consisted of return-to-sport outcomes as well as the
      Western Ontario Shoulder Instability Index (WOSI), Single Assessment Numeric
      Evaluation (SANE), American Shoulder and Elbow Sur'geons (ASES) score, and
      Shoulder Activity Scale. Results: A total of 151 patients were successfully
      contacted (anterior: n = 81; posterior: n = 22; combined: n = 48) at a mean
      follow-up of 3.6 years. No significant differences were found between the groups
      with regard to age at the time of surgery or time to follow-up. No significant
      differences were found between the groups in terms of WOSI (anterior: 76;
      posterior: 70; combined: 78; P = .28), SANE (anterior: 87; posterior: 85;
      combined: 87; P = .79), ASES (anterior: 88; posterior: 83; combined: 91; P =
      .083), or Shoulder Activity Scale (anterior: 12.0; posterior: 12.5; combined:
      12.5; P = .74) scores. No significant difference was found between the groups in
      terms of the rate of return to sport (anterior: 73%; posterior: 68%; combined:
      75%; P = .84). Conclusion: Athletes undergoing arthroscopic stabilization of
      anterior, posterior, or combined shoulder instability can be expected to share a
      similar prognosis. High patient-reported outcome scores and moderate to high
      rates of return to sport were achieved by all groups.

PMID- 29637086
TI  - Outsourcing of Academic Clinical Laboratories: Experiences and Lessons From the
      Association of Pathology Chairs Laboratory Outsourcing Survey.
AB  - American hospitals are increasingly turning to service outsourcing to reduce
      costs, including laboratory services. Studies of this practice have largely
      focused on nonacademic medical centers. In contrast, academic medical centers
      have unique practice environments and unique mission considerations. We sought to
      elucidate and analyze clinical laboratory outsourcing experiences in US academic
      medical centers. Seventeen chairs of pathology with relevant experience were
      willing to participate in in-depth interviews about their experiences.
      Anticipated financial benefits from joint venture arrangements often eroded after
      the initial years of the agreement, due to increased test pricing, management
      fees, duplication of services in support of inpatients, and lack of incentive for
      utilization control on the part of the for-profit partner. Outsourcing can
      preclude development of lucrative outreach programs; such programs were
      successfully launched in several cases after joint ventures were either avoided
      or terminated. Common complaints included poor test turnaround time and problems
      with test quality (especially in molecular pathology, microbiology, and flow
      cytometry), leading to clinician dissatisfaction. Joint ventures adversely
      affected retention of academically oriented clinical pathology faculty, with
      adverse effects on research and education, which further exacerbated clinician
      dissatisfaction due to lack of available consultative expertise. Resident
      education in pathology and in other disciplines (especially infectious disease)
      suffered both from lack of on-site laboratory capabilities and from lack of
      teaching faculty. Most joint ventures were initiated with little or no input from
      pathology leadership, and input from pathology leadership was seen to have been
      critical in those cases where such arrangements were declined or terminated.

PMID- 29637087
TI  - Scientific authorship and collaboration network analysis on malaria research in
      Benin: papers indexed in the web of science (1996-2016).
AB  - Background: To sustain the critical progress made, prioritization and a
      multidisciplinary approach to malaria research remain important to the national
      malaria control program in Benin. To document the structure of the malaria
      collaborative research in Benin, we analyze authorship of the scientific
      documents published on malaria from Benin. Methods: We collected bibliographic
      data from the Web Of Science on malaria research in Benin from January 1996 to
      December 2016. From the collected data, a mulitigraph co-authorship network with
      authors representing vertices was generated. An edge was drawn between two
      authors when they co-author a paper. We computed vertex degree, betweenness,
      closeness, and eigenvectors among others to identify prolific authors. We further
      assess the weak points and how information flow in the network. Finally, we
      perform a hierarchical clustering analysis, and Monte-Carlo simulations. Results:
      Overall, 427 publications were included in this study. The generated network
      contained 1792 authors and 116,388 parallel edges which converted in a weighted
      graph of 1792 vertices and 95,787 edges. Our results suggested that prolific
      authors with higher degrees tend to collaborate more. The hierarchical clustering
      revealed 23 clusters, seven of which form a giant component containing 94% of all
      the vertices in the network. This giant component has all the characteristics of
      a small-world network with a small shortest path distance between pairs of three,
      a diameter of 10 and a high clustering coefficient of 0.964. However, Monte-Carlo
      simulations suggested our observed network is an unusual type of small-world
      network. Sixteen vertices were identified as weak articulation points within the
      network. Conclusion: The malaria research collaboration network in Benin is a
      complex network that seems to display the characteristics of a small-world
      network. This research reveals the presence of closed research groups where
      collaborative research likely happens only between members. Interdisciplinary
      collaboration tends to occur at higher levels between prolific researchers.
      Continuously supporting, stabilizing the identified key brokers and most
      productive authors in the Malaria research collaborative network is an urgent
      need in Benin. It will foster the malaria research network and ensure the
      promotion of junior scientists in the field.

PMID- 29637089
TI  - Child health: what should be done?

PMID- 29637090
TI  - Substandard medicines: a greater problem than counterfeit medicines?

PMID- 29637088
TI  - Appendectomy versus non-operative treatment for acute uncomplicated appendicitis
      in children: study protocol for a multicentre, open-label, non-inferiority,
      randomised controlled trial.
AB  - Background: Appendectomy is considered the gold standard treatment for acute
      appendicitis. Recently the need for surgery has been challenged in both adults
      and children. In children there is growing clinician, patient and parental
      interest in non-operative treatment of acute appendicitis with antibiotics as
      opposed to surgery. To date no multicentre randomised controlled trials that are
      appropriately powered to determine efficacy of non-operative treatment
      (antibiotics) for acute appendicitis in children compared with surgery
      (appendectomy) have been performed. Methods: Multicentre, international,
      randomised controlled trial with a non-inferiority design. Children (age 5-16
      years) with a clinical and/or radiological diagnosis of acute uncomplicated
      appendicitis will be randomised (1:1 ratio) to receive either laparoscopic
      appendectomy or treatment with intravenous (minimum 12 hours) followed by oral
      antibiotics (total course 10 days). Allocation to groups will be stratified by
      gender, duration of symptoms (> or <48 hours) and centre. Children in both
      treatment groups will follow a standardised treatment pathway. Primary outcome is
      treatment failure defined as additional intervention related to appendicitis
      requiring general anaesthesia within 1 year of randomisation (including recurrent
      appendicitis) or negative appendectomy. Important secondary outcomes will be
      reported and a cost-effectiveness analysis will be performed. The primary outcome
      will be analysed on a non-inferiority basis using a 20% non-inferiority margin.
      Planned sample size is 978 children. Discussion: The APPY trial will be the first
      multicentre randomised trial comparing non-operative treatment with appendectomy
      for acute uncomplicated appendicitis in children. The results of this trial have
      the potential to revolutionise the treatment of this common gastrointestinal
      emergency. The randomised design will limit the effect of bias on outcomes seen
      in other studies. Trial registration number: clinicaltrials.gov: NCT02687464.
      Registered on Jan 13th 2016.

PMID- 29637091
TI  - A protocol for quality improvement programme to reduce central line-associated
      bloodstream infections in NICU of low and middle income country.
AB  - Introduction: Central line-associated bloodstream infections (CLABSI) are the
      most important cause of morbidity and mortality in critically ill patients.
      Evidence-based interventions when used in form of a bundle have proven to
      decrease CLABSI. Our unit has a high CLABSI rate (9/1000 central line days).
      Therefore, we intend to introduce evidence-based CLABSI prevention package in our
      practice to improve CLABSI rates in our NICU within limited resources. Methods
      and analysis: The study will be conducted using preanalysis and postanalysis
      design from January 2016 to December 2017. It is going to be conducted in three
      phases with phase I being the preimplimentation phase where retrospective data
      will be collected. Phase II, implementation phase, where the CLABSI prevention
      package will be introduced and phase III will be follow-up to see the impact.
      Primary outcome will be reduction in CLABSI rates. Analysis plan and reporting:
      For all three phases, descriptive analysis will be performed. Nominal data will
      be presented as mean+/-SD, whereas categorical data will be presented as
      frequencies and percentages. To compare the effect of intervention we will use
      independent sample t-test for continuous outcomes, whereas Chi2 test will be used
      for categorical outcomes. Relative risk ratios, 95% CI, and p values will be
      determined. Incidence density will be calculated and Poisson regression will be
      used to determine factors associated with incidence of CLABSI. Microbiological
      profiles and antimicrobial resistance pattern will be reported as pan sensitive,
      multidrug-resistant organism and carbapenem-resistant organism. SQUIRE V.2.0
      guidelines will be used for manuscript writing and reporting.

PMID- 29637092
TI  - Pressure-related flow rates for continuous renal replacement therapy in very
      small children: an in vitro study.
AB  - Objective: Continuous renal replacement therapy (CRRT) is extremely challenging
      in very small children, as most CRRT intravascular access devices are too large.
      We aimed to quantify flow rates through several alternative intravascular
      devices. Design: Experimental in vitro study simulating CRRT. Setting: Whole milk
      and equine blood were used as human blood substitutes due to similar viscosity.
      Milk under gravity pressure was run through a standard CRRT circuit. Equine blood
      was run through a working CRRT machine. Subjects: Eight intravenous access
      devices used in paediatrics, with a variety of connectors. Interventions: Devices
      were tested with milk for flow between 50 and 200 mm Hg pressure, and with blood
      for pressure at flows between 20 and 50 mL/min. Main outcome measures: Flows at
      each input pressure with milk, and pressures at each flow rate with blood.
      Results: With both experimental systems, 8Fr and 6.5Fr haemodialysis catheters,
      and 18G and 20G cannulae allowed excellent low pressure flow rates. 5Fr triple
      central catheter, 5Fr and 4Fr umbilical venous catheter, and 5Fr haemodialysis
      catheters did not allow flows at reasonable pressures for CRRT. A three-way tap
      did not impede flows, but a needle-free valve did. Flows increased with pressure
      non-linearly, presumably due to increasing turbulence. Conclusions: In very small
      patients needing CRRT, where large haemodialysis catheters cannot be used due to
      the patient size, we advise the use of two 18G cannulae in different sites. A
      three-way tap can be added, but not any other connectors. In vitro this system
      gave suitable flow rates with some flexibility for in vivo variations.

PMID- 29637093
TI  - Setting up and running a paediatric emergency department in a hospital in Malawi:
      15 years on.
AB  - Paediatric emergency care is not recognised as a specialty in many countries in
      Africa but is being practised increasingly. Setting up a paediatric emergency
      care unit takes time and often involves trial and error. Here we describe the
      start of the paediatric emergency department in Blantyre, Malawi, a low-income
      country and how it has continued to evolve over 15 years, in the hope that our
      experience will inform and assist others who are already developing their own
      emergency unit or wishing to do so.

PMID- 29637094
TI  - Development of a core outcome set for clinical trials in childhood constipation:
      a study using a Delphi technique.
AB  - Objective: Patients, their parents and healthcare professionals (HCPs) have a
      different perception regarding the symptoms of functional constipation (FC).
      Consequently, a lack of agreement exists on definitions and outcomes used in
      therapeutic trials of FC. Therefore, our aim was to develop a core outcome set
      (COS) for FC for children aged 0-1 year and 1-18 years. Design and setting:
      Prospective study design: primary, secondary and tertiary care settings. Methods:
      This COS was developed using a Delphi technique. First, HCPs, parents of children
      with FC and patients aged >=12-18 years were asked to list up to five outcomes
      they considered relevant in the treatment of FC. Outcomes mentioned by >10% of
      participants were included in a shortlist. In the next phase, outcomes on this
      shortlist were rated and prioritised by HCPs, parents and patients. Outcomes with
      the highest scores were included in a draft COS. In a face-to-face expert
      meeting, the final COS was determined. Results: The first phase was completed by
      109 HCPs, 165 parents and 50 children. Fifty HCPs, 80 parents and 50 children
      completed the subsequent phase. The response rate was between 63% and 100% in
      both steps. The final COS for all ages consisted of: defecation frequency, stool
      consistency, painful defecation, quality of life, side effects of treatment,
      faecal incontinence, abdominal pain and school attendance. Conclusion: The use of
      this COS for FC will decrease study heterogeneity and improve comparability of
      studies. Therefore, researchers are recommended to use this COS in future
      therapeutic trials on childhood FC.

PMID- 29637095
TI  - Survey of nutritional practices during therapeutic hypothermia for hypoxic
      ischaemic encephalopathy.
AB  - Objective: To evaluate current nutritional practices during and after therapeutic
      hypothermia (TH) for infants with hypoxic-ischaemic encephalopathy (HIE) in UK
      neonatal units. Study design: Email survey of neonatal clinicians. Setting: UK
      neonatal units providing active TH. Patients: Neonates cooled for HIE. Methods:
      Email survey including questions regarding the timing of starting enteral feeds,
      volumes, frequency and parenteral nutrition (PN) use and availability of
      guidelines. Results: Forty-nine responses were received (49/69, 71%). The rate of
      enteral feeding during TH and rewarming was 59% (29/49). There was a significant
      linear trend for the increase in the proportion of units starting enteral feeds
      (p=0.001) during TH. As compared with post-TH period, significantly lower milk
      volumes were started during TH (median (range): 7.5 mL/kg/day (1.5-24) vs 17.5
      mL/kg/day (7.5-30), p=0.0004). During TH, breast milk was primarily used by 52%
      of units predominantly as 2-3 hourly feeds, and volumes were increased as
      tolerated in 55% of units. Only 29% (14/49) of units used PN, with 86% (12/14) of
      those offering enteral feeds during PN. Guidelines for feeding during TH were
      available in 31% (15/49) of units. Conclusions: Many neonatal clinicians offer
      enteral feeds predominantly using expressed breast milk, with or without PN,
      during TH, although with huge variability. The heterogeneity in the nutritional
      practice underscores the need for assessing the safety of both enteral and
      parenteral feeding during TH.

PMID- 29637096
TI  - Plasma citrate concentration: a possible biomarker for glaucoma in children.
AB  - Objectives: The main aim of the present study was to examine a possible role of
      plasma and urine citrate levels as glaucoma indicators in school-aged children
      with glaucoma diagnosis. Patients: 34 school-aged children with a glaucoma
      diagnosis (mean age 15.69+/-1.86 years) were qualified for the study group and 34
      patients with no ophthalmological ailments were qualified for the control group
      (mean age 16.1+/-1.98 years). Plasma and urine citrate levels in the study and
      the control group (Kruskal-Wallis test) were compared. Results: Plasma citrate
      levels in the study (16.33+/-4.51 mg/L) and the control group (19.11+/-3.66 mg/L)
      were different; the statistical significance (p=0.0036). Plasma citrate
      concentrations were significantly lower in the study group in comparison with the
      control group. There were no statistically important differences between the
      study group (291.12+/-259.13 mg/24 hours; 275.82+/-217.57 mg/g) and the control
      group (434.88+/-357.66 mg/24 hours; 329.81+/-383.27 mg/g) including urine citrate
      level (p=0.052) and urine citrate to creatine ratio (p=0.4667). Conclusion:
      Plasma citrate concentration might be considered as glaucoma biomarker in
      paediatric population.

PMID- 29637097
TI  - Physiological stress responses in infants at 29-32 weeks' postmenstrual age
      during clustered nursing cares and standardised neurobehavioural assessments.
AB  - Objective: To compare the physiological stress responses of infants born <30
      weeks' gestational age when undergoing clustered nursing cares with standardised
      neurobehavioural assessments in neonatal nurseries. Design/methods: Thirty-four
      infants born <30 weeks' gestation were recruited from a tertiary neonatal
      intensive care unit. Heart rate (HR) and oxygen saturation were recorded during
      clustered nursing cares and during standardised neurobehavioural assessments
      (including the General Movements Assessment, Hammersmith Neonatal Neurological
      Examination and Premie-Neuro Assessment). Two assessors extracted HR and oxygen
      saturations at 5 s intervals, with HR instability defined either as tachycardia
      (HR >180 beats per minute (bpm)) or bradycardia (HR <100 bpm). Oxygen
      desaturations were defined as SpO2<90%. Physiological stability was compared
      between nursing cares and neurobehavioural assessments using linear (for
      continuous outcomes) and logistic (HR instability and oxygen desaturation)
      regression. Results: Compared with clustered nursing cares HR was lower (mean
      difference -5.9 bpm; 95% CI -6.5 to 5.3; P<0.001) and oxygen saturation higher
      (mean difference 2.4%; 95% CI 2.1% to 2.6%; P<0.001) during standardised
      neurobehavioural assessments. Compared with clustered nursing cares
      neurobehavioural assessments were also associated with reduced odds of
      tachycardia (OR 0.44, 95% CI 0.22 to 0.86), HR instability (OR 0.43, 95% CI 0.22
      to 0.85) and oxygen desaturation (OR 0.43, 95% CI 0.26 to 0.70). Conclusions:
      Standardised neurobehavioural assessments are associated with less physiological
      stress than clustered nursing cares in infants aged 29-32 weeks' postmenstrual
      age, and are therefore possible without causing undue physiological disturbance
      in medically stable infants.

PMID- 29637098
TI  - Responding to the changing burden of disease for children and adolescents in
      modern Britain: the RCPCH State of Child Health Report 2017.
AB  - The Royal College of Paediatrics and Child Health published the State of Child
      Health (SOCH) 2017, summarising the changing burden of disease in UK children and
      young people (CYP) over the past 20 years. These data show clearly that the three
      great challenges of our time for CYP are obesity, mental health problems and the
      impact of poverty and inequality on health. In this review, we summarise key
      findings from SOCH 2017 and outline key responses the UK must make to improve
      health and well-being for its CYP.

PMID- 29637099
TI  - Non-pathological bilious vomiting complicating therapeutic hypothermia for
      hypoxic ischaemic encephalopathy in neonates: a retrospective cohort study.
AB  - Objective: Therapeutic hypothermia (TH) for moderate-to-severe neonatal hypoxic
      ischaemic encephalopathy (HIE) is generally described as safe. We performed this
      study to determine the incidence of bilious vomiting or bilious drainage (BVD)
      attributable to TH in this population. Design: A single-centre, retrospective
      cohort study. Setting: Neonatal and paediatric intensive care units (NICU and
      PICU) of a single tertiary care centre. Patients: All newborns with HIE who met
      criteria for TH between 2009 and 2014. Interventions: Cases were matched 1:1 for
      unit of care (NICU vs PICU), gestational age, gender, and Sarnat score with
      historic controls who did not receive TH. Groups were compared with Pearson's
      Chi2 analysis. Relative risk was calculated, and ORs were used to allow
      regression analysis. Results: Forty-seven patients met all inclusion criteria.
      The incidence of BVD in patients who received TH was 26%. The group exposed to TH
      was more likely to experience BVD compared with the control group with a relative
      risk of 6.0(95% CI 1.4 to 25.4), even after accounting for improper or unchecked
      nasogastric position, opioids and muscle relaxant use, OR=7.8(95% CI 1.4 to
      43.3), and when positive blood culture was included in the regression model,
      OR=11.6(95% CI 1.2 to 115.0). Three patients underwent investigation and no
      patients had surgical pathology. Conclusion: TH appears to be associated with non
      pathological bilious vomiting or gastric drainage. Further prospective data are
      needed to identify the patients in whom investigation and intervention may be
      avoided.

PMID- 29637100
TI  - Parent views on the content and potential impact of respiratory tract infection
      surveillance information: semistructured interviews to inform future research.
AB  - Objectives: This study explored the potential value of real-time information
      regarding respiratory tract infections (RTIs) circulating in the community by
      eliciting parent views on illustrative surveillance information and its possible
      impact on primary care consultations. Design: Semistructured interviews were
      conducted with parents of children (>3 months-15 years). Participants were
      presented with example information on circulating viruses, symptoms and symptom
      duration and asked about its potential impact on perceptions of child illness and
      management practices. Interviews were analysed using the framework method.
      Setting: Parents participating in a cohort study were selected purposefully using
      index of multiple deprivation and child age. Participants: 30 mothers of children
      (>3 months-15years). Results: Parents anticipated using the information to inform
      lay diagnoses particularly when child symptoms were severe and thought normal
      symptom duration awareness might extend the time prior to seeking medical advice,
      but it also may encourage consultations when symptoms exceed the given duration.
      The information was not expected to change consultation behaviour if parents felt
      their child needed a medical evaluation and they felt unable to manage the
      symptoms. Most parents felt that the information could provide reassurance that
      could reduce intention to consult, but some felt it could raise concerns, by
      heightening awareness of circulating viruses. Lastly, parents wanted advice about
      protecting children from circulating viruses and felt that general practitioners
      using the information to diagnose child RTIs with greater certainty was
      acceptable. Conclusions: Diverse responses to the surveillance information were
      elicited, and there was some support for the intended outcomes. This study has
      important implications for the design of interventions to modify consulting
      behaviour. Future piloting to measure behaviour change in response to infection
      surveillance information are needed.

PMID- 29637101
TI  - Retrospective review of paediatric case reports of Stevens-Johnson syndrome and
      toxic epidermal necrolysis with lamotrigine from an international
      pharmacovigilance database.
AB  - Objectives: This study aims to characterise paediatric reports with lamotrigine
      (LTG) and Stevens-Johnson syndrome or toxic epidermal necrolysis (SJS/TEN), and
      to explore whether potential risk factors can be identified. Design: This is a
      retrospective review of suspected adverse drug reaction (ADR) reports. Reported
      time from LTG start to SJS/TEN onset, indication for use and dose was explored.
      To identify potential risk groups, report features (eg, ages, patient sex, co
      reported drugs) for LTG and SJS/TEN were contrasted with two reference groups in
      the same database, using shrinkage logOR. Setting: Reports were retrieved from
      VigiBase, the WHO global database of individual case safety reports, in January
      2015. Patients: Data for patients aged <=17 years old were extracted. Results:
      There were 486 reports of SJS/TEN in LTG-treated paediatric patients. Ninety
      seven per cent of the cases with complete information on time to onset of SJS/TEN
      occurred within 8 weeks of initiation of LTG therapy. The median time to onset
      was 15 days (IQR: 10-22 days). The proportion of SJS/TEN with LTG and valproic
      acid (VPA) co-reporting was significantly more than non-cutaneous ADRs (43% vs
      19%, (logOR: 1.60 (99% CI: 1.33 to 1.84)). Conclusions: The results suggest that
      VPA co-medication with LTG therapy is a risk factor for SJS/TEN in the paediatric
      population. Although this relationship has been identified from individual case
      reports, this is the first supportive study from a large compilation of cases.
      SJS/TEN risk is highest in first 8 weeks of treatment with LTG in children and
      clinicians should be aware of this risk during this period.

PMID- 29637102
TI  - Multicentre prospective observational study of feeding practices in 30-33 weeks
      preterm infants.
AB  - Background: Current evidence supports progressive feeding in preterm infants. Due
      to lower necrotising enterocolitis risk, recent studies suggest starting total
      enteral feeding from birth in 30-33 weeks preterm infants. The feasibility of
      this practice is unclear. Aim: Explore feeding practices in 30-33 weeks preterm
      infants. Design: Prospective, multicentre, observational study recruiting 10
      consecutive 30-33 weeks preterm infants from each of the eight UK hospitals.
      Results: Eighty infants received their first feed at median of 24 hours,
      achieving total enteral (without intravenous nutrition) and full feeds (>=150
      ml/kg/day) at median of 5 and 8 days, respectively. Eleven infants who achieved
      total enteral feeding within 24 hours after birth achieved full feeds earlier
      (p=0.02) with shorter hospital stay (p=0.009) but were also of older gestation
      (p=0.004). Conclusion: Current early feeding approaches in 30-33 weeks preterm
      infants were found to be conservative. Total enteral feeding from birth is
      possible in these infants but further studies are needed.

PMID- 29637103
TI  - An international survey of management of pain and sedation after paediatric
      cardiac surgery.
AB  - Objective: The mainstay of pain treatment after paediatric cardiac surgery is the
      use of opioids. Current guidelines for its optimal use are based on small, non
      randomised clinical trials, and data on the pharmacokinetics (PK) and
      pharmacodynamics (PD) of opioids are lacking. This study aims at providing an
      overview of international hospital practices on the treatment of pain and
      sedation after paediatric cardiac surgery. Design: A multicentre survey study
      assessed the management of pain and sedation in children aged 0-18 years after
      cardiac surgery. Setting: Pediatric intensive care units (PICU)of 19 tertiary
      children's hospitals worldwide were invited to participate. The focus of the
      survey was on type and dose of analgesic and sedative drugs and the tools used
      for their pharmacodynamic assessment. Results: Fifteen hospitals (response rate
      79%) filled out the survey. Morphine was the primary analgesic in most hospitals,
      and its doses for continuous infusion ranged from 10 to 60 mcg kg-1 h-1 in
      children aged 0-36 months. Benzodiazepines were the first choice for sedation,
      with midazolam used in all study hospitals. Eight hospitals (53%) reported
      routine use of sedatives with pain treatment. Overall, type and dosing of
      analgesic and sedative drugs differed substantially between hospitals. All
      participating hospitals used validated pain and sedation assessment tools.
      Conclusion: There was a large variation in the type and dosing of drugs employed
      in the treatment of pain and sedation after paediatric cardiac surgery. As a
      consequence, there is a need to rationalise pain and sedation management for this
      vulnerable patient group.

PMID- 29637104
TI  - Developing, implementing and disseminating a core outcome set for neonatal
      medicine.
AB  - Background: In high resource settings, 1 in 10 newborn babies require admission
      to a neonatal unit. Research evaluating neonatal care involves recording and
      reporting many different outcomes and outcome measures. Such variation limits the
      usefulness of research as studies cannot be compared or combined. To address
      these limitations, we aim to develop, disseminate and implement a core outcome
      set for neonatal medicine. Methods: A steering group that includes parents and
      former patients, healthcare professionals and researchers has been formed to
      guide the development of the core outcome set. We will review neonatal trials
      systematically to identify previously reported outcomes. Additionally, we will
      specifically identify outcomes of importance to parents, former patients and
      healthcare professionals through a systematic review of qualitative studies.
      Outcomes identified will be entered into an international, multi-perspective
      eDelphi survey. All key stakeholders will be invited to participate. The Delphi
      method will encourage individual and group stakeholder consensus to identify a
      core outcome set. The core outcome set will be mapped to existing, routinely
      recorded data where these exist. Discussion: Use of a core set will ensure
      outcomes of importance to key stakeholders, including former patients and
      parents, are recorded and reported in a standard fashion in future research.
      Embedding the core outcome set within future clinical studies will extend the
      usefulness of research to inform practice, enhance patient care and ultimately
      improve outcomes. Using routinely recorded electronic data will facilitate
      implementation with minimal addition burden. Trial registration number: Core
      Outcome Measures in Effectiveness Trials (COMET) database: 842 (www.comet
      initiative.org/studies/details/842).

PMID- 29637105
TI  - Supply of unlicensed medicines to children: semi-structured interviews with
      carers.
AB  - Objectives: To explore the experiences of parents and carers relating to the
      supply of unlicensed medicines for their child after discharge from hospital.
      Methods: Semi-structured interviews were conducted with 15 parents and carers of
      children who were newly prescribed an unlicensed medicine. Interviews were
      conducted at least 4 weeks after the child's discharge from hospital. Qualitative
      thematic analysis of the data was carried out. Results: Problems were frequently
      encountered by parents when attempting to obtain further supplies of their
      child's unlicensed medicine. Problems included general practitioners (GPs)
      refusing to prescribe the medicine, GPs prescribing a dose or formulation that
      differed to what had been prescribed previously, pharmacists who were unable to
      source a suitable medicine, medicines that were not labelled with administration
      instructions and delays in obtaining the medicine. Action or intervention by the
      parent was often required to overcome the problems faced. The necessity of these
      actions or interventions, and the implication of not succeeding, frequently
      caused parents anxiety, frustration and dissatisfaction. Conclusions: Strategies
      for improving the process of medicine supply during the transition between
      secondary and primary care are necessary and must involve greater communication
      among healthcare professionals and carers. GPs and community pharmacists should
      have access to greater support and guidance to facilitate the safe prescribing
      and supply of unlicensed medicines. Parents and carers should be informed about
      the process to ensure understanding, create empowerment and to build
      relationships between them and the professionals responsible for the care of
      their child.

PMID- 29637106
TI  - Cost of assessing a child for possible autism spectrum disorder? An observational
      study of current practice in child development centres in the UK.
AB  - Objective: UK guidelines recommend that diagnosis of autism in children requires
      assessment by a multidisciplinary team. With growing numbers of referrals for
      assessment, diagnostic services have been under increasing pressure to meet the
      level of need. This study aimed to explore the number of hours of professional
      time required to complete such an assessment based on current practice in
      secondary care child development centres across the UK, and from this we
      calculate the cost of assessment. Design: An online questionnaire, using
      SurveyMonkey.com, was sent to 20 child development centres asking them to
      retrospectively record team members involved at each stage of assessment and time
      taken, including report writing and administration for a typical assessment.
      Costs were estimated based on the hourly rate for each team member, including
      salary, on-costs and trust overheads. Results: 12 questionnaires (60%) were
      returned. 10 centres adopted a two-stage approach to assessment with an initial
      'screening' clinic determining whether the child needed to proceed to full
      multidisciplinary assessment. Median professional time involved was 13 hours (IQR
      9.6-15.5 hours). This resulted in a median cost of L809 ($1213, based on
      conversion rate L1 equal to US$1.5 (November 2015)), (IQR L684-L925) ($1026
      $1388)). Implications: This study confirms that multidisciplinary diagnostic
      assessment of a child with possible autism requires significant professional
      time, with staff costs of approximately L800 ($1200) per child. This does not
      include costs of intervention, parent psychological education, investigation and
      assessment and management of comorbidities. If growing waiting times for
      diagnostic assessment are to be avoided, funding for diagnostic services needs to
      reflect the human resources required and the resulting costs of that assessment.

PMID- 29637107
TI  - Inequalities in child health in India.
AB  - India is a lower-middle-income country with one of the fastest growing economies
      in the world. Despite improvements in its economy, it has a high child mortality
      rate, with significant differences in child mortality both between and within
      different states. Poverty, malnutrition and poor sanitation are major problems
      for many Indians and are a major contributor to child mortality. More than 40%
      children are malnourished or stunted. Healthcare provision is poor, and many
      families, especially in rural areas, have major difficulties in accessing
      healthcare. Kerala has the lowest child mortality rates in India. This has been
      achieved by reducing poverty, malnutrition and inequalities. The provision of
      universal education alongside universal access to healthcare has demonstrated
      that child mortality rates could be reduced. India could significantly reduce its
      child mortality by following the example of Kerala.

PMID- 29637108
TI  - Impact of perinatal asphyxia on parental mental health and bonding with the
      infant: a questionnaire survey of Swiss parents.
AB  - Objective: To compare current mental health symptoms and infant bonding in
      parents whose infants survived perinatal asphyxia in the last 2 years with
      control parents and to investigate which sociodemographic, obstetric and neonatal
      variables correlated with parental mental health and infant bonding in the
      asphyxia group. Design: Cross-sectional questionnaire survey of parents whose
      children were registered in the Swiss national Asphyxia and Cooling register and
      of control parents (Post-traumatic Diagnostic Scale, Hospital Anxiety and
      Depression Scale, Mother-to-Infant Bonding Scale). Results: The response rate for
      the asphyxia group was 46.5%. Compared with controls, mothers and fathers in the
      asphyxia group had a higher frequency of post-traumatic stress disorder (PTSD)
      symptoms (p<0.001). More mothers (n=28, 56%) had a symptom diagnosis of either
      full or partial PTSD than controls (n=54, 39%) (p=0.032). Similarly, more fathers
      (n=31, 51%) had a symptom diagnosis of either partial or full PTSD than controls
      (n=19, 33%) (p=0.034). Mothers reported poorer bonding with the infant (p=0.043)
      than controls. Having a trauma in the past was linked to more psychological
      distress in mothers (r=0.31 (95% CI 0.04 to 0.54)) and fathers (r=0.35 (95% CI
      0.05 to 0.59)). For mothers, previous pregnancy was linked to poorer bonding
      (r=0.41 (95% CI 0.13 to 0.63)). In fathers, therapeutic hypothermia of the infant
      was related to less frequent PTSD symptoms (r=-0.37 (95% CI -0.61 to -0.06)) and
      past psychological difficulties (r=0.37 (95% CI 0.07 to 0.60)) to more
      psychological distress. A lower Apgar score was linked to poorer bonding (r=-0.38
      (95% CI -0.64 to -0.05)). Conclusions: Parents of infants hospitalised for
      perinatal asphyxia are more at risk of developing PTSD than control parents.

PMID- 29637109
TI  - Variation in the management of SSRI-exposed babies across England.
AB  - Background: Depression in pregnancy is commonly treated using selective serotonin
      reuptake inhibitors (SSRIs). A possible withdrawal syndrome following in utero
      exposure has been reported, but there is currently no UK guidance on the
      management of these neonates. Methods: All 160 neonatal units in England were
      asked for information regarding their management of SSRI-exposed babies. Results:
      Responses were obtained from 112/160 (70%) units. Only four units had a specific
      protocol for managing SSRI-exposed neonates. Twenty-one units (19%) conduct
      routine observations on exposed neonates, while 37 units (33%) would consider
      treating babies with signs of withdrawal or toxicity. Conclusions: Very few
      neonatal units in England have specific guidelines for the management of babies
      exposed to SSRIs in utero, with practice varying greatly between units. Further
      research is needed on the outcomes of SSRI-exposed babies to support development
      of standardised evidence-based guidelines to ensure all mothers and babies
      receive similar high-quality care.

PMID- 29637110
TI  - Is arterial stiffening associated with adiposity, severity of obesity and other
      contemporary cardiometabolic markers in a community sample of adolescents with
      obesity in the UK?
AB  - Background: Cardiovascular disease (CVD) prediction is problematic within groups
      of obese adolescents as measures such as adiposity and metabolic markers lack
      validation. Pulse wave velocity (PWV), a proxy for arterial stiffening, is a
      potential way to contemporaneously capture adolescents at greater risk of CVD.
      Objectives: To investigate associations between PWV and 1) adiposity and 2) other
      conventional metabolic factors in a community sample of (>95th centile body mass
      index (BMI)). Design and setting: Cross-sectional measurement and analysis in a
      hospital-based research centre drawn from a community sample of adolescents
      recruited to an obesity intervention at baseline. Patients: 174 adolescents (12
      19 years) with obesity (>95th centile BMI). 37% were male, while 66 (38%) were
      white, 53 (30%) black, 36 (21%) South Asian, 19 (11%) mixed/other. Participants
      with endocrine, genetic causes of obesity and chronic medical conditions
      (excluding asthma) were excluded. Measures: BMI z-score (zBMI), waist z-score,
      fat mass index (FMI: measured using bioimpedance), sagittal abdominal dimension
      (SAD), cardiometabolic blood tests and resting blood pressure (BP) were
      collected. Carotid-radial PWV was measured by a single operator. Results: PWV was
      associated with age but not pubertal stage. PWV was positively associated with
      adiposity (zBMI: coefficient 0.44 (95% CI 0.08 to 0.79); FMI: coefficient 0.05
      (95% CI 0.00 to 0.10); waist z-score: coefficient 0.27 (95% CI 0.00 to 0.53);
      SAD: coefficient 0.06 (95% CI: 0.00 to 0.12)). There was no association between
      PWV and BP, and few associations with cardiometabolic bloods. Associations
      between PWV and adiposity measures were robust to adjustment in multivariable
      models except for SAD. Participants with zBMI >2.5 SD and >3.5 SD had greater
      average PWV but overlap between groups was large. Conclusions: In our sample,
      increasing adiposity was positively associated with arterial stiffness, however
      partitioning by severity was not reliable. Lack of associations between BP,
      cardiometabolic bloods and arterial stiffness questions the reliability of these
      factors for predicting CVD risk in adolescents with obesity.

PMID- 29637111
TI  - Body image: a survey of children in Caribbean Bonaire.
AB  - Background: In Bonaire, the prevalence of overweight and obesity is twice as high
      compared with Northern Europe but similar to other Caribbean Islands and the USA.
      Having a realistic body image may be an important tool in the battle against
      childhood obesity. Previous studies have demonstrated associations between having
      a realistic body image and efforts to control weight. The aim of the study was to
      explore the body image of children in Bonaire. Methods: In a cross-sectional
      study from March to May 2015 in Bonaire, weight and height were measured in all
      children aged 10-14 years attending school. Body mass index (kg/m2) was
      classified according to the International Obesity Task Force. The children were
      asked about their body image using a validated questionnaire. Results: Body mass
      index was measured in 939 of 1029 (91.3%) children aged 10-14 years (51.5% boys)
      in Bonaire. Of all children, 9.7% was underweight, 57.6% was normal weight, 32.7%
      was overweight (including obesity) and 11.6% was obese. The question pertaining
      to body image was completed by 750 of 939 (79.9%) children. Having a realistic
      perception of body image varied per weight category from 65% in underweight girls
      to 13% in obese boys. The percentage of obese children who underestimate their
      weight is high (boys 87%, girls 77%). Conclusions: In many children in Caribbean
      Bonaire, perceived body image is not in agreement with actual weight status. This
      applies especially to obese children. Disagreement between perceived body image
      and actual weight status may prevent weight management in overweight children.
      Future research is needed to elucidate determinants of disagreement between body
      image and actual weight status.

PMID- 29637112
TI  - Effectiveness of transcutaneous bilirubin measurement in managing neonatal
      jaundice in postnatal ward of a tertiary care hospital in Pakistan.
AB  - Introduction: Neonatal jaundice is a common cause of concern in immediate newborn
      period for parents as well as for the caregivers. Babies with visible jaundice
      are identified by the healthcare provider, and blood samples are sent for
      confirmation. Clinical expertise varies from person to person and may lead to
      sending excessive blood sampling. Obtaining blood bilirubin samples is a painful
      procedure; it predisposes the baby to infections and requires skilled health
      personnel. Moreover, laboratory tests are costly and time consuming, leading to
      unnecessary delays in commencing phototherapy and discharge from hospital.
      Transcutaneous bilirubinometer has been in use for a long time as screening tool
      in postnatal wards. With passage of time, its accuracy and validity have improved
      tremendously. Methodology: We aim to implement a quality improvement initiative
      to reduce the number of blood bilirubin samples using transcutaneous bilirubin
      (TcBR) nomogram in full-term, low-risk babies who are born at our hospital and
      are admitted in postnatal ward after birth. Using preanalysis and postanalysis
      study design, this study will be performed in two phases of 6 months each. Data
      regarding total number of admissions in postnatal wards, demographics, serum
      bilirubin(TSBR) samplings and need for phototherapy will be recorded in both
      phases. TcBR will be done and recorded in postimplementation phase. Analysis and
      results: Comparisons between the two groups will be made. Primary outcome will be
      reduction in blood bilirubin samples for TSBR after the implementation of TcBr
      protocol. The proportion of infants having TSBR performed in both periods will be
      compared. Crude sampling cost of TSBR will be obtained from laboratory, and cost
      comparison between two phases will be done to look for difference.

PMID- 29637113
TI  - Probiotics for the prevention of surgical necrotising enterocolitis: systematic
      review and meta-analysis.
AB  - Aim of the study: Probiotic administration to preterm infants has the potential
      to prevent necrotising enterocolitis (NEC). Data from randomised controlled
      trials (RCT) are conflicting but meta-analyses seem to support this intervention.
      To date, these analyses have not focused on surgical NEC. We aimed to determine
      the effect of probiotic administration to preterm infants on prevention of
      surgical NEC. Methods: A systematic review of RCTs of probiotic administration to
      preterm infants was performed. Studies were included if RCT outcomes included any
      of (1) Bell's stage 3 NEC; (2) surgery for NEC; and (3) deaths attributable to
      NEC. Article selection and data extraction were performed independently by two
      authors; conflicts were adjudicated by a third author. Data were meta-analysed
      using Review Manager V.5.3. A random effects model was decided on a priori
      because of the heterogeneity of study design; data are risk ratio (RR) with 95%
      CI. Main results: Thirty-five RCTs reported NEC as an outcome. Seventeen reported
      surgical NEC; all RCTs were included. A variety of probiotic products was
      administered across studies. Description of surgical NEC in most studies was
      poor. Only 6/16 specifically reported incidence of surgery for NEC, 12/17 Bell's
      stage 3 and 13/17 NEC-associated mortality. Although there was a trend towards
      probiotic administration reducing stage 3 NEC, this was not significant (RR 0.74
      (0.52-1.05), p=0.09). There was no effect of probiotics on the RR of surgery for
      NEC (RR 0.84 (0.56-1.25), p=0.38). Probiotics did, however, reduce the risk of
      NEC-associated mortality (RR 0.56 (0.34-0.93), p=0.03). Conclusion: Despite 35
      RCTs on probiotic prevention of NEC, evidence for prevention of surgical NEC is
      not strong, partly due to poor reporting. In studies included in this meta
      analysis, probiotic administration was associated with a reduction in NEC-related
      mortality.

PMID- 29637114
TI  - Intrapartum intravenous fluids for caesarean delivery and newborn weight loss: a
      retrospective cohort study.
AB  - Objective: To examine weight loss (WL) and excess weight loss (EWL) among
      newborns of caesarean delivery, comparing colloids plus crystalloids versus
      crystalloids only. Also, to examine different doses of intrapartum intravenous
      fluids on WL and EWL. Design: Comparative safety retrospective cohort study.
      Setting: University Teaching Hospital, Moncton, Canada. Patients: Mothers exposed
      to intravenous fluids with caesarean delivery between 2008 and 2016.
      Interventions: Exposure to colloids plus crystalloids was compared with
      crystalloids only, and dose-response analyses were performed for colloids,
      crystalloids and total intravenous fluids doses. Linear and logistic regression
      models were used, adjusting for potential confounders. Main outcome measures:
      Infants' WL was measured at days 1, 2 and 3 post partum, and EWL defined as loss
      of >7% of birth weight. Results: From 801 mother-infant pairs, 176 were exposed
      to colloids plus crystalloids and 625 were exposed to crystalloids only (overall
      mean birth weight=3416 g, EWL=2%, 41.4% and 55.5% on days 1, 2 and 3,
      respectively). No significant difference in newborns' WL was observed on any of
      the days assessed. Adjusted OR (95% CI) of EWL was 1.0 (0.3 to 3.3) at 24 hours,
      1.0 (0.7 to 1.5) at 48 hours and 1.4 (0.9 to 2.2) at 72 hours. No dose-response
      relationship was detected with type-specific and total intravenous fluids
      exposures. Conclusions: The risk of EWL was similar with colloids plus
      crystalloids and crystalloids only, suggesting that both therapeutic options can
      be considered during caesarean delivery. The absence of dose-response
      relationships adds confirmatory evidence to the intravenous fluids safety
      profiles.

PMID- 29637115
TI  - Laboratory reference intervals in the assessment of iron status in young
      children.
AB  - Objectives: The primary objective was to establish reference intervals for
      laboratory tests used to assess iron status in young children using the Clinical
      and Laboratory Standards Institute guidelines. A secondary objective was to
      compare the lower limit of the reference interval with the currently recommended
      cut-off value for haemoglobin and serum ferritin in children 1-3 years of age.
      Methods: Blood samples were obtained from healthy children recruited during
      scheduled health supervision visits with their primary care physician. For our
      primary objective, outliers were removed; age partitions were selected and
      analysis of variance and pairwise comparisons were made between adjacent
      partitions; reference intervals and 90% CIs were calculated. For our secondary
      objective, we determined the proportion of children misclassified using the lower
      limit reference interval compared with the cut-off value. Results: Samples from
      2305 male and 2029 female participants (10 days to 10.6 years) were used to
      calculate age and sex-specific reference intervals for laboratory tests of iron
      status. There were statistically significant differences between adjacent age
      partitions for most analytes. Approximately 10% of children 1-3 years of age were
      misclassified (underestimated) using the lower limit of the reference intervals
      rather than the currently recommended cut-off values for haemoglobin and serum
      ferritin. Implications and relevance: Clinical laboratories may consider adopting
      published paediatric reference intervals. Reference intervals may misclassify
      (underestimate) children with iron deficiency as compared with currently
      recommended cut-off values. Future research on decision limits derived from
      clinical studies of outcomes is a priority.

PMID- 29637117
TI  - Management of anaphylaxis in children: a survey of parents and school personnel
      in Qatar.
AB  - Background: Allergies are a growing health concern with a significant impact on
      quality of life and healthcare costs. It is critical to develop an appropriate
      care plan to deal with children's allergies. This study aimed to assess and
      compare the knowledge and perception of families and school personnel caring for
      children with history of anaphylaxis who were prescribed the epinephrine
      autoinjector (EpiPen). The study also examined the underlying reasons for any
      observed knowledge gaps. Methods: A cross-sectional study of 128 families and 50
      corresponding school personnel caring for children at risk of anaphylaxis who had
      been prescribed the EpiPen was conducted. The primary outcome was to identify any
      knowledge deficiency within family and school personnel and the reasons behind
      knowledge gaps. Results: Of the 128 screened schools, 30 (23%) were not informed
      by parents about their pupils' risk of anaphylaxis. Importantly, 113 (88%) of
      families and 42 (84%) of schools were unable to recognise the symptoms of
      anaphylaxis. Also, 67 (52%) of families and 22 (44%) of schools were not aware
      that a child should ideally have two EpiPen in case of a severe allergic
      reaction. The EpiPen had been used by 18 (14%) families and 5 (6%) schools.
      Discussion: Communication among families and school personnel regarding
      anaphylaxis was suboptimal. Both parents and school personnel lacked key
      information in allergy management. Managing a child at risk of anaphylaxis
      requires effective communication among healthcare professionals, families and
      schools. There is an urgent need to improve knowledge of anaphylaxis and its
      management among families and school caregivers.

PMID- 29637116
TI  - Swim drink study: a randomised controlled trial of during-exercise rehydration
      and swimming performance.
AB  - Objective: To determine whether during-exercise rehydration improves swimming
      performance and whether sports drink or water have differential effects on
      performance. Design: Randomised controlled multiple crossover trial. Setting: A
      UK competitive swimming club. Subjects: 19 club-level competitive swimmers,
      median age (range) 13 (11-17) years. Interventions: Subjects were scheduled to
      drink ad libitum commercial isotonic sports drink (3.9 g sugars and 0.13 g salt
      per 100 mL) or water (three sessions each) or no drink (six sessions) in the
      course of twelve 75 min training sessions, each of which was followed by a 30 min
      test set of ten 100 m maximum-effort freestyle sprints each starting at 3 min
      intervals. Main outcome measure: Times for the middle 50 m of each sprint
      measured using electronic timing equipment in a Federation Internationale de
      Natation (FINA)-compliant six-lane 25 m competition swimming pool. Randomisation:
      Software-generated individual random session order in sealed envelopes. Analysis
      subset of eight sessions randomly selected by software after data collection
      completed. Masking: Participants blind to drink allocation until session start.
      Results: In the analysis data set of 1118 swims, there was no significant
      difference between swim times for drinking and not drinking nor between drinking
      water or a sports drink. Mean (SEM) 50 m time for no-drink swims was 38.077
      (0.128) s and 38.105 (0.131) s for drink swims, p=0.701. Mean 50 m times were
      38.031 (0.184) s for drinking sports drink and 38.182 (0.186) s for drinking
      water, p=0.073. Times after not drinking were 0.027 s faster than after drinking
      (95% CI 0.186 s faster to 0.113 s slower). Times after drinking sports drink were
      0.151 s faster than after water (95% CI 0.309 s faster to 0.002 s slower). Mean
      (SEM) dehydration from exercise was 0.42 (0.11)%. Conclusions: Drinking water or
      sports drink over 105 min of sustained effort swimming training does not improve
      swimming performance. Trial registration: ISRCTN: 49860006.

PMID- 29637118
TI  - Task-specific gross motor skills training for ambulant school-aged children with
      cerebral palsy: a systematic review.
AB  - Objectives: The primary objective is to systematically evaluate the evidence for
      the effectiveness of task-specific training (TST) of gross motor skills for
      improving activity and/or participation outcomes in ambulant school-aged children
      with cerebral palsy (CP). The secondary objective is to identify motor learning
      strategies reported within TST and assess relationship to outcome. Design:
      Systematic review. Method: Relevant databases were searched for studies
      including: children with CP (mean age >4 years and >60% of the sample ambulant);
      TST targeting gross motor skills and activity (skill performance, gross motor
      function and functional skills) and/or participation-related outcomes. Quality of
      included studies was assessed using standardised tools for risk of bias, study
      design and quality of evidence across outcomes. Continuous data were summarised
      for each study using standardised mean difference (SMD) and 95% CIs. Results:
      Thirteen studies met inclusion criteria: eight randomised controlled trials
      (RCTs), three comparative studies, one repeated-measures study and one single
      subject design study. Risk of bias was moderate across studies. Components of TST
      varied and were often poorly reported. Within-group effects of TST were positive
      across all outcomes of interest in 11 studies. In RCTs, between-group effects
      were conflicting for skill performance and functional skills, positive for
      participation-related outcomes (one study: Life-HABITS performance SMD=1.19, 95%
      CI 0.3 to 2.07, p<0.001; Life-HABITS satisfaction SMD=1.29, 95% CI 0.40 to 2.18,
      p=0.001), while no difference or negative effects were found for gross motor
      function. The quality of evidence was low-to-moderate overall. Variability and
      poor reporting of motor learning strategies limited assessment of relationship to
      outcome. Conclusions: Limited evidence for TST for gross motor skills in ambulant
      children with CP exists for improving activity and participation-related outcomes
      and recommendations for use over other interventions are limited by poor study
      methodology and heterogeneous interventions. Registration: PROSPERO
      ID42016036727.

PMID- 29637119
TI  - Infrared thermography in paediatrics: a narrative review of clinical use.
AB  - Background: Infrared thermography (IRT) has been used in adult medicine for
      decades, but recent improvements in quality of imaging and increasing computer
      processing power have allowed for a diversification of clinical applications. The
      specific usage of IRT in a paediatric population has not been widely explored, so
      this article aims to summarise the available literature in this area. IRT
      involves the non-contact, accurate measurement of skin surface temperature to
      identify temperature changes suggesting disease. IRT could well have unique
      applications in paediatric medicine. Methods: Electronic searches were performed
      independently by two authors, using the databases of MEDLINE (via Web of
      Science), the Cochrane Library, CINAHL (EBSCO) and Scopus, including articles
      published from 1990 to July 2016. The search strategy that was used aimed to
      include articles that covered the topics of IRT and children, including studies
      with participants 18 years old or younger. Articles were screened by title and
      abstract by two authors. Meta-analysis was not performed due to the marked
      heterogeneity in applications, study design and outcomes: this is a narrative
      summary of the available literature. Results: IRT has been shown to be an
      effective additional diagnostic tool in a number of different paediatric
      specialties, namely in fracture screening, burns assessment and neonatal
      monitoring. Small measurable skin temperature changes can effectively add to the
      clinical picture, while computer-tracking systems can be reliably used to focus
      investigations on particular areas of the body. Conclusion: Throughout this
      review of the available literature, there has been a general consensus that this
      non-invasive, non-irradiating and relatively inexpensive technology may well have
      a place in the management of paediatric patients in the future.

PMID- 29637120
TI  - Validation of a classification system for treatment-related mortality in children
      with cancer.
AB  - Background: Death not directly due to cancer has been termed 'treatment-related
      mortality' (TRM). Appreciating the differences between TRM and disease-related
      death is critical in directing strategies to improve supportive care,
      interventions delivered or disease progression. Recently, a global collaboration
      developed and validated a consensus-based classification tool and attribution
      system. Objectives: To evaluate the reliability of the newly developed consensus
      based definition of TRM and explore the use of the cause-of-death attribution
      system outside the centre it was initially validated (Toronto, Canada). In the
      initial study, reviewers listed multiple causes of death. In this study,
      reviewers identified a primary cause for simplicity. Setting: The paediatric
      haematology and oncology department at Leeds Teaching Hospital in Leeds, UK.
      Participants: Two consultants and two clinical research associates (CRAs).
      Methods: Thirty medical records of the most recent deaths in children with
      cancer, 2 and 4 weeks prior to death, were anonymised and presented to the
      participants. Reviewers independently classified deaths as 'treatment related
      mortality' or 'not treatment related' according to the algorithm developed. When
      TRM occurred, reviewers applied the cause-of-death attribution system to identify
      the primary cause of death. Inter-relater reliability was assessed using the
      kappa statistic (k). Main outcome: Inter-relater reliability between CRA and
      consultants. Results: Reliability of the classification was deemed 'very good'
      between CRA and consultants (k=0.86, 95% CI 0.72 to 0.97). Ten deaths were
      classified as TRM, of which infection was the most frequent cause identified.
      Reviewers disagreed on the primary cause of death (eg, respiratory vs infection)
      when applying the cause-of-death attribution system in six cases and probable and
      possible causes in four cases. The study identified how the algorithm may not
      detect TRM in patients receiving non-curative therapy. Conclusions: The
      classification and cause of death attribution system could be implemented in
      different healthcare settings. Adaptation of the classification tool in patients
      receiving non-curative interventions and the cause of death attribution system
      should be considered.

PMID- 29637121
TI  - Improved oxygen systems in district hospitals in Lao PDR: a prospective field
      trial of the impact on outcomes for childhood pneumonia and equipment
      sustainability.
AB  - Background: Hypoxaemia is a common and potentially fatal complication of many
      childhood, newborn and maternal conditions but often not well recognised or
      managed in settings where resources are limited. Oxygen itself is often
      inaccessible due to cost or logistics. This paper describes implementation of
      oxygen systems in Lao district hospitals, clinical outcomes after 24 months and
      equipment outcomes after 40 months postimplementation. Methods: A prospective
      field trial was conducted in 20 district hospitals, including 10 intervention
      hospitals that received oxygen concentrators and 10 control hospitals. Equipment
      outcomes were evaluated at baseline, 12, 24 and 40 months. Clinical outcomes of
      children under 5 years of age with pneumonia were evaluated using a before-and
      after controlled study design with information retrospectively collected from
      medical records. Results: Fourteen (37%), 7 (18%) and 12 (34%) of 38
      concentrators required repair at 12, 24 and 40 months, respectively. The
      proportion of children discharged well increased in intervention (90% (641/712)
      to 95.2% (658/691)) and control hospitals (87.1% (621/713) to 92.1% (588/606)).
      In intervention hospitals, case fatality rates for childhood pneumonia fell from
      2.7% (19/712) preintervention to 0.80% (6/691) postintervention with no change in
      control hospitals (1.7% (12/713) preintervention and 2.3% (14/606)
      postintervention). Conclusion: Medium-term sustainability of oxygen concentrators
      in hospitals accompanied by reduced case fatality for childhood pneumonia has
      been demonstrated in Lao PDR. Significant local engineering capacity to address
      multiple causes of equipment malfunction was critical. The ongoing requirements
      and fragile structures within the health system remain major risks to long-term
      sustainability.

PMID- 29637123
TI  - Armed conflict and child mental health.

PMID- 29637122
TI  - Protocol for a randomised control trial of bisphosphonate (zoledronic acid)
      treatment in childhood femoral head avascular necrosis due to Perthes disease.
AB  - Introduction: Perthes disease (PD) is an idiopathic disorder presenting with
      avascular necrosis to the femoral head, which frequently results in flattening.
      Long-term function is directly related to the subsequent femoral head sphericity.
      Current treatment includes mechanical modalities and surgical procedures, which
      are therapeutic but are not uniformly able to prevent collapse. The use of the
      nitrogen-containing bisphosphonate zoledronic acid (ZA) to inhibit osteoclastic
      bone resorption is aimed at preserving femoral head strength, reducing collapse
      and thus maintaining shape. The proposed multicentre, prospective, randomised
      controlled trial intends to evaluate the efficacy of ZA treatment in PD. Methods
      and analysis: An open-label randomised control trial recruiting 100 children (50
      each treatment arm) 5 to 16 years old with unilateral PD. Subjects are randomly
      assigned to either (a) ZA and standard care or (b) Standard care. The primary
      outcome measure is deformity index (DI), a radiographic parameter of femoral head
      roundness assessed at 24 months, following 12 months of ZA treatment (3-monthly
      doses of ZA 0.025 mg/kg at baseline, 3, 6, 9 and 12 months) plus 12 months
      observation (group A) or 24 months of observation (group B). Secondary outcome
      measures are femoral head subluxation, Faces Pain scale, Harris hip score and
      quality of life. Assessments are made at baseline, 3 monthly during the first
      year of follow-up and then 6 monthly, until the 24th month. Ethics and
      dissemination: The study commenced following the written approval from the Human
      Research Ethics Committee. Safety considerations regarding the effects of ZA are
      monitored which include the subject's symptomatology, mineral status, bone mass
      and turnover activity, and metaphyseal modelling. Data handling plan requires
      that all documents, clinical information, biological samples and investigation
      results will be held in strict confidence by study investigators to preserve its
      safety and confidentiality. Trial registration number: Australian and New Zealand
      Clinical Trials ACTRN12610000407099, pre-results.

PMID- 29637124
TI  - Anti-epileptic drug utilisation in paediatrics: a systematic review.
AB  - Objectives: This study aims to determine global anti-epileptic drug (AED)
      utilisation prevalence and describe utilisation trends in different countries.
      Methods: Databases Embase (1980-May 2017), Medline (1946-May 2017) and PubMed
      were searched for original research on AED utilisation. All paediatric national
      or regional database studies and surveys were included. Results: Twenty-one
      studies were identified. Five were excluded from the analysis as the data were
      collected before 2005, leaving 16 studies. Monotherapy regimen varied between 58%
      and 94% in different countries. In several of the studies, sodium valproate was
      the most frequently prescribed AED. However, there is a trend towards increasing
      utilisation of new-generation AEDs, particularly levetiracetam, in some
      countries. Conclusion: Monotherapy was used in 58%-94%of patients. There is
      increasing utilisation of the new-generation AEDs, in particular lamotrigine,
      levetiracetam and topiramate. Old-generation AEDs are still used in the majority
      of patients. There is a need for up-to-date studies to determine the prevalence
      of AEDs in children.

PMID- 29637125
TI  - Retrospective audit of guidelines for investigation and treatment of
      bronchiolitis: a French perspective.
AB  - Introduction: As the most recent French bronchiolitis guidelines were published
      in 2000, there is a current overinvestigation and an overtreatment of infants
      hospitalised with bronchiolitis in France. In 2012, the Group of Pediatric
      University Hospitals in Western France ('HUGO') proposed new evidence-based
      clinical practice guidelines in keeping with the latest international guidelines.
      We hypothesise that the implementation of these guidelines contributed to the
      quality improvement of the management of bronchiolitis in our hospital. The aim
      of this study was to determine the impact of these guidelines on the management
      of bronchiolitis inpatients. Methods: This retrospective before/after study
      design was conducted in the general paediatric unit of a tertiary care French
      hospital, looking at 1 year before (ie, the winter of 2011-2012) and 1 year after
      (ie, the winter of 2013-2014) the implementation of the guidelines. Two hundred
      and eighty bronchiolitis inpatients, all less than 1 year of age, 115 in 2011
      2012 and 165 in 2013-2014, were included. The primary outcome we sought to
      evaluate was the proportion of children administered a diagnostic test associated
      with a treatment not routinely recommended by the guidelines. As balancing
      measures, we evaluated the length of stay, the intensive care unit transfer and
      the readmission rates. Results: Following implementation of the guidelines, use
      of any given treatment associated with a diagnostic test was reduced by 66%
      (p<0.001). There were major decreases in the use of chest X-ray (86%vs26%,
      p<0.001), antibiotics (38%vs13%, p<0.001) and corticosteroids (10%vs3%, p=0.011).
      Balancing measures were not significantly different. Conclusions: HUGO guidelines
      were effective at reducing the administration of unnecessary diagnostic tests and
      medications. This study was the first step in convincing French paediatricians to
      streamline their practices until updated national guidelines are published.

PMID- 29637126
TI  - Assessment of developmental outcome in very low birth weight infants in Southern
      Africa using the Bayley Scales of Infant Development (III).
AB  - Objectives: The study aimed to compare the developmental outcome of very low
      birth weight infants with a group of normal-term controls in a tertiary hospital
      in sub-Saharan Africa. Design: A group of 105 very low birth weight infants were
      assessed at a mean age of 17.6 months (95% CI 16.7 to 18.6) using the Bayley
      Scales of Infant Development, Third Edition, and compared with a group of normal
      term controls at the same mean age. Results: Seven of the study infants (7%) had
      developmental delay (a score below 70), compared with none in the control group
      (p=0.04). Three of the seven study infants were delayed on all three subscales,
      one of whom had cerebral palsy. A further 34% of the study infants were 'at risk'
      of developmental delay (a score below 85). There was no difference in the mean
      composite score between the study group and controls for the cognitive (p=0.56),
      motor (p=0.57) or language (p=0.66) subscales. There was no difference in mean
      composite scores on all subscales between infants who were appropriate for
      gestational age and those who were small for gestational age. Cognitive and motor
      scores remained stable in paired assessments of study infants before and after 1
      year of age; language scores decreased significantly (p<0.001). Mechanical
      ventilation was the only risk factor significantly associated with a cognitive
      score below 85 in study infants. Conclusion: Very low birth weight infants in sub
      Saharan Africa are at risk of developmental delay and require long-term
      neurodevelopmental follow-up.

PMID- 29637127
TI  - Peripheral blood RNA gene expression in children with pneumococcal meningitis: a
      prospective case-control study.
AB  - Introduction: Invasive pneumococcal disease (IPD), caused by Streptococcus
      pneumoniae, is a leading cause of pneumonia, meningitis and septicaemia
      worldwide, with increased morbidity and mortality in HIV-infected children.
      Objectives: We aimed to compare peripheral blood expression profiles between HIV
      infected and uninfected children with pneumococcal meningitis and controls, and
      between survivors and non-survivors, in order to provide insight into the host
      inflammatory response leading to poorer outcomes. Design and setting: Prospective
      case-control observational study in a tertiary hospital in Malawi. Participants:
      Children aged 2 months to 16 years with pneumococcal meningitis or pneumonia.
      Methods: We used the human genome HGU133A Affymetrix array to explore differences
      in gene expression between cases with pneumococcal meningitis (n=12) and
      controls, and between HIV-infected and uninfected cases, and validated gene
      expression profiles for 34 genes using real-time quantitative PCR (RT-qPCR) in an
      independent set of cases with IPD (n=229) and controls (n=13). Pathway analysis
      was used to explore genes differentially expressed. Results: Irrespective of
      underlying HIV infection, cases showed significant upregulation compared with
      controls of the following: S100 calcium-binding protein A12 (S100A12); vanin-1
      (VNN1); arginase, liver (ARG1); matrix metallopeptidase 9 (MMP9); annexin A3
      (ANXA3); interleukin 1 receptor, type II (IL1R2); CD177 molecule (CD177);
      endocytic adaptor protein (NUMB) and S100 calcium-binding protein A9 (S100A9),
      cytoskeleton-associated protein 4 (CKAP4); and glycogenin 1 (GYG1). RT-qPCR
      confirmed differential expression in keeping with microarray results. There was
      no differential gene expression in HIV-infected compared with HIV-uninfected
      cases, but there was significant upregulation of folate receptor 3 (FOLR3),
      S100A12 in survivors compared with non-survivors. Conclusion: Children with IPD
      demonstrated increased expression in genes regulating immune activation,
      oxidative stress, leucocyte adhesion and migration, arginine metabolism, and
      glucocorticoid receptor signalling.

PMID- 29637128
TI  - Effect of socioeconomic conditions on frequent complaints of pain in children:
      findings from the UK Millennium Cohort Study.
AB  - Background: Frequent complaints of pain (FCP) are common in high-income
      countries, affecting about 25% of children, and may have significant adverse
      consequences including prolonged school absence and disability. Most FCP are
      unexplained, and the aetiology is poorly understood. This study aimed to identify
      risk factors for FCP and explore how risk factors explain variation in pain
      reporting by childhood socioeconomic conditions (SECs). Methods: Analysis of the
      UK Millennium Cohort Study, including 8463 singleton children whose parents
      provided data throughout the study. At 11 years, mothers were asked whether their
      child frequently complains of pain. Risk ratios (RR) and 95% CIs for FCP were
      estimated using Poisson regression, according to maternal education. Other risk
      factors were explored to assess if they attenuated any association between FCP
      and SECs. Results: 32.3% of children frequently complained of pain. Children of
      mothers with no educational qualifications were more likely to have FCP than
      children of mothers with higher degrees (RR 2.06, 95% CI 1.64 to 2.59) and there
      was a clear gradient across the socioeconomic spectrum. Female sex, fruit
      consumption, childhood mental health and maternal health measures were associated
      with childhood FCP in univariable and multivariable analyses. Inclusion of these
      factors within the model attenuated the RR by 17% to 1.70 (95% CI 1.36 to 2.13).
      Conclusion: In this representative UK cohort, there was a significant excess of
      FCP reported in less advantaged children that was partially attenuated when
      accounting for indicators of parental and childhood mental health. Addressing
      these factors may partially reduce inequalities in childhood FCP.

PMID- 29637129
TI  - Parental characteristics and functional constipation in children: a cross
      sectional cohort study.
AB  - Objective: To evaluate personality, psychological health, physical health and
      childrearing practices in mothers and fathers of children with functional
      constipation (FC) compared with mothers and fathers of healthy controls. Design:
      Cross-sectional cohort study. Setting: Outpatient paediatric gastroenterology
      clinic at a tertiary hospital in the Netherlands. Patients: Parents of children
      (4-16 years) presenting with FC were included between January 2010 and August
      2012. Participating parents were asked to recruit parents of another child of the
      same age without FC as their own controls. Data of 116 mothers and 115 fathers of
      127 children with FC, and 84 mothers and 73 fathers of 91 children without FC
      were collected. Main outcome measures: Parental characteristics were evaluated by
      using the NEO Five-Factor Inventory to assess personality, the Brief Symptom
      Inventory and Physical Symptom Checklist to assess psychological and physical
      health and the Ghent Parental Behavior Scale to assess childrearing practices.
      Results: Mothers of constipated children had significant higher scores on the
      neuroticism personality factor and reported higher rates of overall psychological
      distress and depression. Both mothers and fathers of children with FC reported
      significant more physical symptoms than parents of children without FC. Mothers
      of children with FC showed more positive childrearing practices compared with
      controls. Conclusions: Personality, psychological and physical health, and
      childrearing practices differ significantly between parents of children with FC
      and parents of control subjects. Parental factors should be taken into account
      when evaluating children with FC.

PMID- 29637130
TI  - How can general paediatric training be optimised in highly specialised tertiary
      settings? Twelve tips from an interview-based study of trainees.
AB  - Objectives: Both general and subspecialty paediatric trainees undertake
      attachments in highly specialised tertiary hospitals. Trainee feedback suggests
      that mismatches in expectations between trainees and supervisors and a perceived
      lack of educational opportunities may lead to trainee dissatisfaction in such
      settings. With the 'Shape of Training' review (reshaping postgraduate training in
      the UK to focus on more general themes), this issue is likely to become more
      apparent. We wished to explore the factors that contribute to a positive
      educational environment and training experience and identify how this may be
      improved in highly specialised settings. Methods: General paediatric trainees
      working at all levels in subspecialty teams at a tertiary hospital were recruited
      (n=12). Semistructured interviews were undertaken to explore the strengths and
      weaknesses of training in such a setting and how this could be optimised.
      Appreciative inquiry methodology was used to identify areas of perceived best
      practice and consider how these could be promoted and disseminated. Results:
      Twelve best practice themes were identified: (1) managing expectations by
      acknowledging the challenges; (2) educational contracting to identify learning
      needs and opportunities; (3) creative educational supervision; (4) centralised
      teaching events; (5) signposting learning opportunities; (6) curriculum-mapped
      pan-hospital teaching programmes; (7) local faculty groups with trainee
      representation; (8) interprofessional learning; (9) pastoral support systems;
      (10) crossover weeks to increase clinical exposure; (11) adequate clinical
      supervision; and (12) rota design to include teaching and clinic time.
      Conclusions: Tertiary settings have strengths, as well as challenges, for general
      paediatric training. Twelve trainee-generated tips have been identified to
      capitalise on the educational potential within these settings. Trainee feedback
      is essential to diagnose and improve educational environments and appreciative
      inquiry is a useful tool for this purpose.

PMID- 29637131
TI  - Advance care planning for adolescent patients with life-threatening neurological
      conditions: a survey of Japanese paediatric neurologists.
AB  - Objective: To evaluate current attitudes and barriers to advance care planning
      for adolescent patients with life-threatening conditions among paediatric
      neurologists. Design: Cross-sectional study. A self-reported questionnaire was
      administered to assess the practice of advance care planning, advance directives
      and barriers to advance care planning for adolescent patients with life
      threatening conditions. All board-certified paediatric neurologists in Japan were
      surveyed and those who had experience in taking care of adolescent patients with
      decision-making capacity were analysed. We compared the results with those of
      paediatric haematologists reported previously. Results: In total, 186 paediatric
      neurologists were analysed. If the patient's prognosis was <3 months, only about
      30% of paediatric neurologists reported having discussions with patients, such as
      'do not attempt resuscitation' orders (28%) and ventilator use (32%), whereas
      more than 70% did discuss these topics with patients' families. About half of the
      paediatric neurologists did not discuss advance directives at the end of life
      with their patients, whereas over 75% did discuss advance directives with
      patients' families. Compared with paediatric haematologists, paediatric
      neurologists had more end-of-life discussions with patients, such as where
      treatment and care will take place, do not attempt resuscitation orders, and the
      use of a ventilator, if the patient's prognosis was >1 year. Conclusion: About
      half or less of the paediatric neurologists discussed advance care planning and
      advance directives with their adolescent patients who had life-threatening
      conditions, even if the patient's prognosis was <3 months. They tended to discuss
      advance care planning and advance directives more with families than with
      patients themselves.

PMID- 29637132
TI  - Improving communication between staff and disabled children in hospital wards:
      testing the feasibility of a training intervention developed through intervention
      mapping.
AB  - Objective: To develop and test the feasibility of a novel parent-inspired
      training intervention for hospital ward staff to improve communication with
      disabled children when inpatients. Design: Training content and delivery
      strategies were informed by the iterative process of Intervention Mapping and
      developed in collaboration with parents of disabled children. Setting: UK
      University Hospital children's ward. Subjects: 80 medical, nursing, allied health
      professionals, clerical and housekeeping staff on a children's ward. Methods:
      Themes identified in previous qualitative research formed the basis of the
      training. Learning objectives included prioritising communication, cultivating
      empathy, improving knowledge and developing confidence. Participant feedback was
      used to refine content and delivery. Intervention documentation adheres to the
      Template for Intervention Description and Replication checklist. Results:
      Highlighting mandated National Health Service policies and involving the hospital
      Patient and Carer Experience Group facilitated management support for the
      training. Eighty staff participated in one of four 1-hour sessions. A paediatric
      registrar and nurse delivered sessions to mixed groups of staff. General feedback
      was very positive. The intervention, fully documented in a manual, includes
      videos of parent carers discussing hospital experiences, interactive tasks, small
      group discussion, personal reflection and intention planning. Generic and local
      resources were provided. Conclusion: It was feasible to deliver this new
      communication training to hospital ward staff and it was positively received.
      Early feedback was encouraging and indicates a commitment to behaviour change.
      Further piloting is required to establish the transferability of the intervention
      to other hospitals, followed by consideration of downstream markers to evaluate
      the effects on disabled children's inpatient experience. Organisational and
      cultural change is required to support individual behaviour change.

PMID- 29637133
TI  - Survey of antiobesity drug prescribing for obese children and young people in UK
      primary care.
AB  - Objectives: Antiobesity drug (AOD) prescribing in children and young people (CYP)
      in primary care is rising with high rates of discontinuation. Little is known
      about prescribing in this group in terms of patient demographics and
      comorbidities, reasons for initiation and discontinuation, or adherence to
      national guidelines. Design: Questionnaire survey to general practitioners (GPs)
      identified using a nationally representative primary care database covering 6% of
      UK population. Setting: UK-wide primary care. Participants: Patients were
      eligible if prescribed an AOD aged <=18 years between 2010 and 2012. A total of
      151 patients from 108 unique practices were identified via national prescribing
      database, with responses for 119 patients (79%) from 84 practices; 94 of 119
      (79%) were eligible for inclusion. Primary and secondary outcomes: Survey of GP
      prescribing habits of AODs to CYP. We audited orlistat usage against the National
      Institute for Health and Care Excellence (NICE) guidance. Results: 47% were
      prescribed metformin, 59% orlistat and 5% both drugs. Orlistat was largely
      prescribed by GPs independently (49/55 prescriptions, 89%) and metformin by GPs
      on specialist recommendation (12/44, 27%). Orlistat was largely prescribed in
      those over 16 years of age without physical comorbidities. Metformin was
      initiated for treatment of polycystic ovarian syndrome (70%), insulin resistance
      (25%) and impaired glucose control (9%). Median supply of metformin was 10.5
      months (IQR 4-18.5 months) and 2.0 months (1.0-4.0) for orlistat (p<=0.001). Drug
      terminations were largely due to families not requesting repeat prescriptions.
      NICE guidance adherence was low; 17% of orlistat prescriptions were initiated by
      specialists, and 56% had evidence of obesity-related comorbidity. GPs reported
      lower confidence in prescribing AOD to CYP compared with adults (10-point Likert
      score median 3 vs 8, p<0.001). Conclusions: Prescribing of AOD in primary care is
      challenging with low adherence to NICE guidance. Further work is needed to better
      support GPs in the use of AOD in CYP.

PMID- 29637135
TI  - Efficacy of an interventional educational programme in mitigating post-traumatic
      stress in parents who have witnessed a febrile seizure: a pilot before-and-after
      study.
AB  - Objectives: To measure post-traumatic stress in parents who have witnessed their
      child's first simple febrile seizure and to assess the impact of workshops where
      information is dispensed, proper reactions are demonstrated and dialogue is
      encouraged on the mitigation of parental stress. Design: A pilot before-and-after
      study, with control group, using self-reported measures from the Impact of Event
      Scale-Revised. Setting: Data from two French participating centres. Participants:
      A total of 50 parents who witnessed their child's first simple febrile seizure.
      Intervention: Parents selected themselves into either group 1: attending a
      workshop (intervention group), or group 2: no further management (control group).
      Primary and secondary outcome measures: (1) Parental post-traumatic stress was
      assessed by the Impact of Event Scale-Revised a minimum of 4 weeks after the
      seizure (before any workshop if applicable). A high risk of developing post
      traumatic stress disorder was indicated by a score >=33. (2) To assess the
      efficacy of workshops on the mitigation of parental stress, all parents self
      completed the Impact of Event Scale-Revised a second time at a minimum of 10
      weeks after the seizure (after any workshop if applicable). Results: Four weeks
      after the seizure, 76% of the total parents presented an Impact of Event Scale
      Revised score >=33. At 10 weeks after the seizure, the scores were 18.1 points
      lower (95% CI 11.66 to 24.61, P<0.0001) in group 1 versus only 5.51 points lower
      (95% CI 2.76 to 8.27, P=0.0003) in group 2 (intragroup comparison), and were
      significantly lower in group 1 compared with group 2 (intergroup comparison),
      P=0.02. Conclusions: Parents who have witnessed their child's first simple
      febrile seizure are at high risk of developing post-traumatic stress disorder 4
      weeks after the seizure. Our innovative workshops are associated with a
      significant mitigation of the parental post-traumatic stress.

PMID- 29637134
TI  - Burden of severe neonatal jaundice: a systematic review and meta-analysis.
AB  - Context: To assess the global burden of late and/or poor management of severe
      neonatal jaundice (SNJ), a common problem worldwide, which may result in death or
      irreversible brain damage with disabilities in survivors. Population-based data
      establishing the global burden of SNJ has not been previously reported.
      Objective: Determine the burden of SNJ in all WHO regions, as defined by clinical
      jaundice associated with clinical outcomes including acute bilirubin
      encephalopathy/kernicterus and/or exchange transfusion (ET) and/or jaundice
      related death. Data sources: PubMed, Scopus and other health databases were
      searched, without language restrictions, from 1990 to 2017 for studies reporting
      the incidence of SNJ. Study selection/data extraction: Stratification was
      performed for WHO regions and results were pooled using random effects model and
      meta-regression. Results: Of 416 articles including at least one marker of SNJ,
      only 21 reported estimates from population-based studies, with 76% (16/21) of
      them conducted in high-income countries. The African region has the highest
      incidence of SNJ per 10 000 live births at 667.8 (95% CI 603.4 to 738.5),
      followed by Southeast Asian, Eastern Mediterranean, Western Pacific, Americas and
      European regions at 251.3 (132.0 to 473.2), 165.7 (114.6 to 238.9), 9.4 (0.1 to
      755.9), 4.4 (1.8 to 10.5) and 3.7 (1.7 to 8.0), respectively. The incidence of ET
      per 10 000 live births was significantly higher for Africa and Southeast Asian
      regions at 186.5 (153.2 to 226.8) and 107.1 (102.0 to 112.5) and lower in Eastern
      Mediterranean (17.8 (5.7 to 54.9)), Americas (0.38 (0.21 to 0.67)), European
      (0.35 (0.20 to 0.60)) and Western Pacific regions (0.19 (0.12 to 0.31). Only 2
      studies provided estimates of clear jaundice-related deaths in infants with
      significant jaundice [UK (2.8%) and India (30.8%). Conclusions: Limited but
      compelling evidence demonstrates that SNJ is associated with a significant health
      burden especially in low-income and middle-income countries.

PMID- 29637136
TI  - Medicines in schools: a cross-sectional survey of children, parents, teachers and
      health professionals.
AB  - Objectives: To describe how individual schools manage medicines and strategies
      for implementation of guidance, to determine the nature of problems perceived by
      children, parents, teachers and healthcare professionals (HCPs) in relation to
      medicines management in schools and to highlight differences between these
      perceptions. Design: A cross-sectional survey study in which questionnaires were
      completed by children, their parents and carers, groups of HCPs and head
      teachers. Results: There were 158 respondents to this survey. The management of
      medicines varies between schools and this reflects how policy guidance is
      interpreted and is revealed by the differences in experience described. Head
      teachers acknowledge that there is a lack of expertise about medicines among
      their staff and they rely on interpretation of and adherence to policy and
      procedure and compliance with training was used as a measure of good medicines
      management. There are inconsistencies in how information about medicines is
      communicated between the healthcare team, families and schools, and there is
      evidence that this communication is not always timely or effective. This results
      in problems with medicines at school. Parents emphasised the need for staff at
      school to understand their child's condition and their medicines. Conclusions:
      There are differences between how individual schools manage medicines and
      interpret policy guidance and discrepancies between the views of each stakeholder
      group. There is some evidence that medicines management does not always meet the
      needs of children and their families. Fewer than half of parents and HCPs are
      satisfied with how medicines are dealt with in schools.

PMID- 29637137
TI  - Perspectives of adolescents on decision making about participation in a biobank
      study: a pilot study.
AB  - Objectives: To be able to truly involve adolescents in decision making about
      clinical research participation, we need more insight in the perspective of
      adolescents themselves. To this end, adolescents in an ongoing biobank study were
      consulted to test a tentative decision assessment tool. Methods: The perspectives
      of adolescents (n=8) concerning participation in decision making for research
      participation were explored in interviews with a tentative tool, which covered
      six topics: information material usage, understanding, disease perceptions,
      anxiety, decision-making process and role sharing. Results: All adolescents
      unequivocally expressed the desire to be involved in decision making, but also
      wanted advice from their parents. The extent of the preferred role of adolescent
      versus parents varied between individuals. In decision making, adolescents relied
      on parents for information. More than half hardly used the information material.
      Conclusions: Adolescents in our study preferred a shared decision-making process.
      The extent of sharing varied between individuals. The decision assessment tool
      was a fruitful starting point to discuss adolescents' perspectives and may aid in
      tailoring the situation to the individual to achieve optimal participation
      practices. Implications: Consulting adolescents about their preferences
      concerning decision making using the tool will facilitate tailoring of the shared
      decision-making process and optimising the developing autonomy of minors.

PMID- 29637138
TI  - Child homicide perpetrators worldwide: a systematic review.
AB  - Objective: This study aims to describe child homicide perpetrators and estimate
      their global and regional proportion to inform prevention strategies to reduce
      child homicide mortality worldwide. Design: A systematic review of 9431 studies
      derived from 18 databases led to the inclusion of 126 studies after double
      screening. All included studies reported a number or proportion of child
      homicides perpetrators. 169 countries and homicide experts were surveyed in
      addition. The median proportion for each perpetrator category was calculated by
      region and overall and by age groups and sex. Results: Data were obtained for 44
      countries. Overall, parents committed 56.5% (IQR 23.7-69.6) of child homicides,
      58.4% (0.0-66.7) of female and 46.8% (14.1-63.8) of male child homicides.
      Acquaintances committed 12.6% (5.9-31.3) of child homicides. Almost a tenth (9.2%
      (IQR 0.0-21.9) of child homicides had missing information on the perpetrator. The
      largest proportion of parental homicides of children was found in high-income
      countries (64.2%; 44.7-71.8) and East Asia and Pacific Region (61.7%; 46.7-78.6).
      Parents committed the majority (77.8% (61.5-100.0)) of homicides of children
      under the age of 1 year. For adolescents, acquaintances were the main group of
      homicide perpetrators (36.9%, 6.6-51.8). There is a notable lack of studies from
      low-income and middle-income countries and children above the age of 1 year.
      Conclusion: Children face the highest risk of homicide by parents and someone
      they know. Increased investment into the compilation of routine data on child
      homicide, and the perpetrators of this homicide is imperative for understanding
      and ultimately reducing child homicide mortality worldwide. Trial registration
      number: PROSPERO registration number: CRD42015030125.

PMID- 29637139
TI  - Access to healthcare for children in Palestine.
AB  - Currently, 5 million Palestinian refugees live in Palestine, Jordan, Syria and
      Lebanon and around 40% of these are children. Mortality rates for Palestinian
      children are comparable to neighbouring Arab countries but the speed of reduction
      has faltered in recent years. Morbidity is greatly affected by the occupation
      which has increased violence towards children, mental health problems and poor
      nutrition, particularly in Gaza which is experiencing a health crisis. Access to
      healthcare for children in Palestine is constrained as a result of the
      requirement for visas to travel into Jerusalem where specialist hospitals are
      sited, by difficulties with ambulance transfers, by shortages of equipment in
      hospitals and by lack of trained staff. Palestinian health workers are developing
      new initiatives in healthcare and show a high level of resilience, despite the
      very considerable stress affecting most citizens.

PMID- 29637140
TI  - Protocol for a prospective observational study of adverse drug reactions of anti
      epileptic drugs in children in the UK.
AB  - Background: Epilepsy is a common chronic disease of children that can be treated
      with anti-epileptic drugs (AEDs). AEDs, however, have significant side effects.
      Newer AEDs are thought to have fewer side effects. There have, however, been few
      comparative studies of AED toxicity. The aim is to compare the safety profile of
      the most frequently used AEDs by performing a multicentre prospective cohort
      study. This protocol describes the planned study. Design: A multicentre
      prospective cohort study of children on AED treatment in hospitals across the UK.
      Ethical approval will be obtained. Sample size: Three thousand children on
      treatment for epilepsy will be recruited from paediatric clinics. It is expected
      that this sample size will have the potential to compare toxicity between the
      most frequently used AEDs. Duration of study: 24 months. Outcome measure: Adverse
      drug reactions (ADRs) to AEDs. These will be identified by the use of a validated
      questionnaire, the Paediatric Epilepsy Side Effect Questionnaire. They will be
      evaluated using the Naranjo algorithm. Preventability will be assessed using the
      Schumock and Thornton scale. Discussion: Toxicity of individual AEDs when given
      as monotherapy and polytherapy will be determined. Additionally, discontinuation
      rates due to ADRs will be determined. The data will assist clinicians in choosing
      AEDs with the least toxicity.

PMID- 29637141
TI  - Bowel preparation for elective procedures in children: a systematic review and
      meta-analysis.
AB  - Objective: Reviews have investigated preparation for colonoscopy, but not for
      surgery, They are also often limited to patients up to 16 years, despite many
      paediatric gastroenterologists caring for older patients. We carried out a
      systematic review investigating the optimum bowel preparation agents for all
      indications in children and young people. Design: A Cochrane format systematic
      review of randomised controlled trials (RCTs). Data extraction and assessment of
      methodological quality were performed independently by two reviewers.
      Methodological quality was assessed using the Cochrane risk of bias tool.
      Patients: Young people requiring bowel preparation for any elective procedure, as
      defined by the primary studies. Interventions: RCTs comparing bowel preparation
      with placebo or other interventions. Main outcome measures: Adequacy of bowel
      preparation, tolerability and adverse events. Results: The search yielded 2124
      results and 15 randomised controlled studies (n=1435)but heterogeneity limited
      synthesis. Meta-analysis of two studies comparing polyethylene glycol (PEG) with
      sodium phosphate showed no difference in the quality of bowel preparation (risk
      ratio (RR) 1.27(95% CI 0.66 to 2.44)). Two studies comparing sodium
      picosulfate/magnesium citrate with PEG found no difference in bowel preparation
      but significantly higher number of patients needing nasogastric tube insertion in
      the polyethylene glycol-electrolyte lavage solution (RR 0.04(95% CI 0.01 to
      0.18), 45 of 117 in PEG group vs 2 of 121 in sodium picosulfate group). Meta
      analysis of three studies (n=241) found no difference between PEG and sennasoids
      (RR 0.73(95% CI 0.31 to 1.71)). Conclusions: The evidence base is clinically
      heterogeneous and methodologically at risk of bias. There is evidence that all
      regimens are equally effective. However, sodium picosulfate was better tolerated
      than PEG. Future research is needed with all agents and should seek to consider
      safety and tolerability as well as efficacy.

PMID- 29637142
TI  - A protocol for whole-exome sequencing in newborns with congenital deafness: a
      prospective population-based cohort.
AB  - Introduction: The aetiology of congenital hearing loss is heterogeneous, and in
      many infants a genetic cause is suspected. Parents face a diagnostic odyssey when
      searching for a cause of their infant's hearing loss. Through the Melbourne
      Genomics Health Alliance, a prospective cohort of infants will be offered whole
      exome sequencing (WES) with targeted analysis in conjunction with chromosome
      microarray to determine the genetic causes of congenital hearing loss. Parents
      will also be offered the opportunity to receive additional results from their
      infant's WES. Methods: Eligible infants will be identified through the Victorian
      Infant Hearing Screening Program and offered an appointment in a paediatrician
      run clinic, a genetics assessment and enrolment in the Victorian Childhood
      Hearing Impairment Longitudinal Databank. If parents consent to WES, genes
      causing deafness will be analysed and they can choose to obtain additional
      findings. For the additional results component, a modified laboratory protocol
      has been designed for reporting of results in the absence of a relevant
      phenotype. Parents' experience of being offered WES will be evaluated using
      surveys. Discussion: This project will provide descriptive analysis of the
      genetic aetiology of congenital hearing loss in this cohort and may provide data
      on genotype-phenotype correlations. Additionally, choices regarding additional
      findings will be analysed. Participants will represent a diverse cross section of
      the population, increasing the ability to generalise results beyond the study
      group. Evaluation surveys will allow analysis of preferences around counselling,
      usefulness of a decision aid and adequacy of information provision.

PMID- 29637143
TI  - Analysis of acute presentations for child protection medical assessments in a
      large, culturally diverse metropolitan setting.
AB  - Objective: South Western Sydney has a large culturally diverse population with
      many vulnerable subgroups; little is known about the health and social outcomes
      following acute child maltreatment assessments. We aimed to describe acute
      presentations of maltreatment in South Western Sydney-including examination
      findings of the assessment, determine health and social outcomes for children
      following medical assessment, to inform service development. Design: We gathered
      data from the acute child protection database on all children <16 years referred
      for physical abuse and neglect and/or sexual abuse assessment between 2013 and
      2015 to one hospital service. We reviewed clinical records of the children
      assessed, using the reports to classify findings of the examination. We performed
      simple descriptive analysis on the data. Results: There were 304 children
      referred, 279 seen for acute assessment. Most (72%) were female, 204 (73%)
      referrals were for sexual abuse, 75 (27%) were for physical abuse and neglect.
      There were age, gender and ethnicity differentials depending on type of
      maltreatment presentation. Twelve per cent of sexual and 19% of physical abuse
      cases were found not to be abuse related. Unmet medical, developmental and
      behavioural concerns were identified in the majority (54%) assessed. Just under
      half (48%) of all children went home with families with no statutory agency
      support; those seen for physical abuse were more likely to be placed in care
      (p<0.001). Conclusions: Children assessed for child maltreatment had a range of
      health and social concerns identified, needing further intervention.
      Comprehensive medical assessments have a critical role to play in child
      protection assessments.

PMID- 29637144
TI  - Effectiveness of preformed foot orthoses in reducing lower limb pain, swollen and
      tender joints and in improving quality of life and gait parameters in children
      with juvenile idiopathic arthritis: a randomised controlled trial (Protocol).
AB  - Background: Many children and adolescents with juvenile idiopathic arthritis
      experience lower limb problems which may lead to physical disabilities
      significantly impacting on their quality of life and symptoms. Emerging evidence
      has identified the effective role of podiatry in the management of juvenile
      idiopathic arthritis, suggesting the clinical benefit of different orthotic
      therapies. Methods: This study will be a parallel-group designed, multicentre,
      randomised controlled trial, aiming to recruit 66 children and adolescents with
      juvenile idiopathic arthritis aged between 5 and 18 years. Those recruited will
      need to be diagnosed according to the International League of Associations for
      Rheumatology criteria, and present with lower limb joint pain, swelling and/or
      tenderness. Participants will be recruited from three outpatient hospital clinics
      in New South Wales, Australia. Participants will be randomly allocated to receive
      a trial or control intervention. The trial group will be prescribed a customised
      preformed foot orthoses; instead, the control group will receive a flat 1 mm
      insole with no corrective modifications. Primary outcome measure recorded will be
      pain. Secondary outcomes will be quality of life, foot disability, swollen and
      tender joint count and gait parameters (such as plantar pressures, walking speed,
      stance and swing time). The allocated foot orthoses will be worn for 12 months,
      with data collected at baseline, 4 weeks, 3, 6 and 12 months intervals. Group
      allocation will be concealed and all analyses will be carried out on an intention
      to treat. Discussion: The purpose of this trial is to explore the efficacy of a
      cost-effective, non-invasive podiatric intervention that will be prescribed at
      the initial biomechanical consultation. This approach will promote early clinical
      intervention, which is the gold standard in paediatric rheumatology. Furthermore,
      this study has the potential to provide new evidence for the effectiveness of a
      mechanical intervention alone to reduce swollen and tender joints in juvenile
      idiopathic arthritis. Trial registration number: This clinical trial has been
      registered with the Australian New Zealand Clinical Trials Registry:
      ACTRN12616001082493p. Ethics for this randomised controlled trial has been
      approved (16/09/21/4.03).

PMID- 29637145
TI  - Osteonecrosis in patients with acute lymphoblastic leukaemia: a national
      questionnaire study.
AB  - Objectives: To establish prevalence, management and long-term outcomes of
      osteonecrosis (ON) in young people diagnosed with acute lymphoblastic leukaemia
      (ALL) between 2003 and 2011. Design setting participants: This study assessed ON
      in 3113 patients aged 1-24 years who participated in the UK national leukaemia
      study UKALL 2003. UKALL 2003 recruited patients in 40 UK hospitals between 2003
      and 2011 and included patients between ages 1 and 25 diagnosed with ALL. Results:
      170 patients were diagnosed with ON, giving a prevalence of 5.5%. The
      multivariable analysis showed that the risk of ON was highest for children aged
      between 10 and 20 years (ages 10-15 years, OR 23.7, 95% CI 14.8 to 38.0; ages 16
      20 years, OR 22.5, 95% CI 12.7 to 39.8, compared with age <10 years). Among
      ethnic groups, Asian patients had the highest risk of ON (OR 1.92, 95% CI 1.1 to
      3.6, compared with White patients). Eighty-five per cent of patients with ON had
      multifocal ON. Thirty-eight per cent of patients with ON required surgery and 19%
      of patients with ON required a hip replacement. Fifteen per cent of patients who
      had surgery still describe significant disability or use of a wheelchair.
      Conclusions: ON has considerable morbidity for patients being treated for ALL,
      with a high burden of surgery. Age and ethnicity were found to be the most
      significant risk factors for development of ON, with Asian patients and patients
      aged 10-20 years at diagnosis of ALL at greatest risk. These results will help
      risk stratify patients at diagnosis of ALL, and help tailor future prospective
      studies in this area.

PMID- 29637146
TI  - Audit of child maltreatment medical assessments in a culturally diverse,
      metropolitan setting.
AB  - Objective: Child maltreatment (CM) is a major public health problem globally.
      While there is evidence for the value of medical examination in the assessment of
      CM, little is known about the quality of clinical assessments for CM. South
      Western Sydney (SWS) has a large metropolitan population with many vulnerable
      subgroups. We aimed to describe acute presentations of CM in SWS over a 3-year
      period-with a focus on the quality of the clinical assessments. We wanted to
      determine whether the cases assessed fulfilled established minimum standards for
      clinical assessment of CM and whether the assessments were performed in a child
      friendly manner. Design: We gathered data from the acute child protection
      database on all children <16 years referred for assessment between 2013 and 2015.
      We performed simple descriptive analysis on the data. We measured the assessment,
      report writing and follow-up against criteria for minimum standards for CM
      assessments, and identified whether assessments were child-friendly from
      available clinical information. Results: There were 304 children referred; 279
      seen for acute assessment; most (73%) were for sexual abuse, 75 (27%) were for
      physical abuse/neglect. Over half the assessments identified other health
      concerns; joint assessments performed by paediatric and forensic doctors were
      better at identifying these health concerns than solo assessments. Most
      assessments were multidisciplinary and used protocols; half were not followed up;
      a third were performed after-hours and a third had no carer present during
      assessments. Conclusions: We identified strengths and weaknesses in current CM
      assessments in our service. Locally relevant standards for CM assessments are
      achievable in the acute setting, more challenging is addressing appropriate
      medical and psychosocial follow-up for these children. While we have established
      baseline domains for measuring a child-friendly approach to CM assessments, more
      should be done to ensure these vulnerable children are assessed in a timely,
      child-friendly manner, with appropriate follow-up.

PMID- 29637147
TI  - Congenital heart disease and the prevalence of underweight and obesity from age 1
      to 15 years: data on a nationwide sample of children.
AB  - Objective: We examined the prevalence of underweight and obesity in children with
      congenital heart disease (CHD) compared with the general population. Methods:
      Using the Danish National Patient Registry, we identified individuals born and
      diagnosed with CHD in Denmark during 1996-2012 who were alive at 1 year of age. A
      unique personal identifier enabled identification of CHD subjects, as well as
      birth year and sex-matched (1:10) general population controls. The Children's
      Database has recorded height and weight measured by clinical providers at
      preventive health checks offered to all children in Denmark. Data recording were
      made mandatory in 2011. Obesity was defined as body mass index (BMI) above the
      95thpercentile and underweight as BMI below the fifth percentile for age and sex.
      We determined the prevalence of underweight and obesity at study subjects' first
      height and weight recording. For those underweight at age 1 year, prevalence of
      underweight and obesity at later recordings was assessed. Results: We identified
      9194 children with CHD of which 2679 (29%) had at least one recording of height
      and weight. The control cohort demonstrated a similar portion of anthropometric
      data: 30 047 (31%) of 96 585 controls. The prevalence of underweight and obesity
      at CHD study subjects' first height and weight recording was 9.7% (95% CI 8.7 to
      11) and 4.1% (95% CI 3.4 to 4.9), respectively. Among individuals with CHD who
      were underweight at age 1 year (n=78), 51 (65%) had additional BMI recordings
      between ages 2 and 5 years with a subsequently diminished prevalence of
      underweight of 27% (95% CI 20 to 35) and none were obese. Conclusion: The CHD
      population had an increased prevalence of underweight compared with the general
      population. Data indicated potential for BMI normalisation among those initially
      underweight at age 1 year. The prevalence of obesity in children with CHD was
      comparable with that of the general population.

PMID- 29637148
TI  - Pilot evaluation of parental and professional views regarding consent in neonatal
      medicine by telephone interviews and questionnaires.
AB  - Objective: The objectives of the study were to determine (1) parental and
      professional views regarding the type of consent required for common neonatal
      interventions and (2) whether there has been a change in professional
      understanding regarding the requirements of consent since the last UK survey in
      2003. Design: Cohort study of (1) parents of babies admitted to a single-centre
      tertiary neonatal unit and (2) healthcare professionals. Methods: The views of 8
      parents of former neonatal patients and 69 neonatal professionals were sought
      using online and telephone survey methodology regarding 20 neonatal interventions
      and whether implied consent, explicit verbal consent or explicit written consent
      should be obtained. Results: Agreement, defined as both parental and professional
      consensus on the type of consent required, was present in 12/20 of the
      interventions. Comparison between professional views in 2003 demonstrated a
      change regarding type of consent for 50% of interventions with a shift towards
      obtaining explicit written consent certain treatments. Conclusions: The study
      indicates areas of consensus that exist between parents and professionals
      regarding consent for common neonatal interventions and a change in professional
      views regarding consent since the last UK survey in 2003. These data might help
      inform the development of national guidance for how professionals should obtain
      consent in neonatology.

PMID- 29637149
TI  - Social stigmatisation in late identified patients with disorders of sex
      development in Indonesia.
AB  - Objectives: To assess social stigmatisation related to atypical appearance of the
      body, including, but not limited to the external genitalia, among Indonesian
      patients with a disorder of sex development (DSD). Until recently, diagnostic
      evaluation, information about the underlying causes of DSD and treatment options
      were sparsely available for these patients. Methods: Eighty-one parents of
      children and adolescents with DSD (aged 6-17 years) and 34 adult patients with
      DSD (aged 18-41 years) completed the Social Stigmatisation Scale towards DSD, an
      instrument developed to assesses the frequency of stigmatisation and the level of
      stress associated with these experiences. Open-ended questions investigated
      detailed information on stigmatisation as well as parents' and patients'
      emotional and behavioural reactions to these experiences. Differences in
      stigmatisation were explored across sex of rearing, gender change history,
      treatment status and DSD characteristics that could be easily identified by
      others (e.g., masculinisation of the body in women). Results: Social
      stigmatisation was reported by patients with atypical appearance of their
      genitalia, atypical appearance of their body aside from their genitals, among
      those who displayed cross-gender behaviour and those who changed gender. Among
      participants reared as women and among children and adolescents who changed
      gender, social stigmatisation was associated with ostracism, depressive symptoms
      and social isolation. Conclusions: Patients unable to conceal their condition
      (those with visible physical atypicality and those who changed gender)
      experienced social stigmatisation. Stigmatisation was stressful and related to
      isolation and withdrawal from social interaction. Education about DSD, self
      empowerment and medical interventions to prevent atypical physical development
      may remove barriers to acceptance by others for affected individuals.

PMID- 29637150
TI  - Understanding the needs of professionals who provide psychosocial care for
      children and adults with disorders of sex development.
AB  - Objective: Disorders in sex development (DSD) can be treated well medically, but
      families will encounter many psychosocial challenges. Promoting counselling to
      facilitate acceptance and coping is important yet equality of access is unknown.
      This study investigated the modalities of psychosocial care provided in centres
      of DSD care. Methods: An international survey conducted among 93 providers of
      psychosocial care, identified through clinical networks, registries and
      professional forums. Results: Forty-six respondents from 22 different countries
      filled out the survey (49%). Most respondents (78%) were based in hospital-based
      expert teams. Referrals came from paediatric endocrinologists (76%),
      gynaecologists (39%) and paediatric urologists (37%). Psychological counselling
      was most frequently given to parents (74%), followed by children (39%),
      adolescents (37%) and adults (11%) and was most frequently focused on coping and
      acceptance of DSD (54%), education (52%), the atypical body (39%) and genital
      (41%), decisions on genital surgery (33%), complications with sexual intercourse
      (29%), disclosure (28%) and acceptance of infertility (11%). Respondents most
      frequently observed DSD related confusion about gender (54%), acceptance of cross
      gender behaviour (50%), anxiety (43%) and sadness and depression (38%).
      Conclusions: Most psychosocial care is provided to parents. It is assumed that
      parental support is important as acceptance is conditional to become affectionate
      caretakers. Although it may be more difficult for youngsters to communicate about
      their condition and treatment, providing opportunity to bring up issues that are
      important for them, is imperative. Clinicians and parents should be aware that
      parental and patients' interests may not correspond completely. Psychosocial
      management should also include transition and adult care.

PMID- 29637151
TI  - Factors influencing maternal decision-making for the infant sleep environment in
      families at higher risk of SIDS: a qualitative study.
AB  - Objective: Qualitative interviews with mothers of babies at higher risk of sudden
      infant death syndrome (SIDS) were carried out to understand their views and
      decision-making process on the infant sleep environment and safe sleep messages.
      Design and setting: Twenty semi-structured interviews were conducted between
      February and November 2014 in deprived areas of Bristol, UK. Mothers were asked
      about their decision-making for the infant sleep environment and safe sleep
      messages including infant sleep position, co-sleeping, smoking, dummy use,
      feeding and disrupted routines. The interviews were transcribed, coded and
      thematic analysis carried out. Participants: Participants were invited based on
      an algorithm developed in a previous SIDS case control study that identified an
      increased risk of SIDS from four demographic characteristics: young maternal age,
      smoking during pregnancy, three or more children, and a measure of deprivation.
      The presence of three, or more characteristics led to being invited to take part
      in the qualitative study. Results: Factors influencing mothers' adherence to the
      safe sleep messages included previous experience and the credibility of the
      advice given. They described disrupted routines that led to risky scenarios with
      a belief that occasional risks were acceptable. Where circumstances made
      following the advice more difficult they found alternative strategies to reduce
      the risk, including the use of movement monitors, regular checking and a belief
      that lighter maternal sleep in the presence of a baby was protective.
      Conclusions: Safer sleep messages should be tailored to fit with the lived
      realities of mothers, especially those at higher risk. The traditional list of
      'do's' and 'don'ts' was not well accepted by this group. Interventions that seek
      to influence this higher-risk group should acknowledge mothers' own protective
      instincts and consider their beliefs and understanding behind the safer sleep
      messages if they are to be effective and encourage this group to change.

PMID- 29637152
TI  - Continuum of neurobehaviour and its associations with brain MRI in infants born
      preterm.
AB  - Background: Infants born very preterm (VPT) and moderate-to-late preterm (MLPT)
      are at increased risk of long-term neurodevelopmental deficits, but how these
      deficits relate to early neurobehaviour in MLPT children is unclear. The aims of
      this study were to compare the neurobehavioural performance of infants born
      across three different gestational age groups: preterm <30 weeks' gestational age
      (PT<30); MLPT (32-36 weeks' gestational age) and term age (>=37 weeks'
      gestational age), and explore the relationships between MRI brain abnormalities
      and neurobehaviour at term-equivalent age. Methods: Neurobehaviour was assessed
      at term-equivalent age in 149 PT<30, 200 MLPT and 200 term-born infants using the
      Neonatal Intensive Care UnitNetwork Neurobehavioral Scale (NNNS), the Hammersmith
      Neonatal Neurological Examination (HNNE) and Prechtl's Qualitative Assessment of
      General Movements (GMA). A subset of 110 PT<30 and 198 MLPT infants had
      concurrent brain MRI. Results: Proportions with abnormal neurobehaviour on the
      NNNS and the HNNE, and abnormal GMA all increased with decreasing gestational
      age. Higher brain MRI abnormality scores in some regions were associated with
      suboptimal neurobehaviour on the NNNS and HNNE. The relationships between brain
      MRI abnormality scores and suboptimal neurobehaviour were similar in both PT<30
      and MLPT infants. The relationship between brain MRI abnormality scores and
      abnormal GMA was stronger in PT<30 infants. Conclusions: There was a continuum of
      neurobehaviour across gestational ages. The relationships between brain
      abnormality scores and suboptimal neurobehaviour provide evidence that
      neurobehavioural assessments offer insight into the integrity of the developing
      brain, and may be useful in earlier identification of the highest-risk infants.

PMID- 29637153
TI  - Digital assessment of the fetal alcohol syndrome facial phenotype: reliability
      and agreement study.
AB  - Purpose: To examine the three facial features of fetal alcohol syndrome (FAS) in
      a cohort of Australian Aboriginal children from two-dimensional digital facial
      photographs to: (1) assess intrarater and inter-rater reliability; (2) identify
      the racial norms with the best fit for this population; and (3) assess agreement
      with clinician direct measures. Methods: Photographs and clinical data for 106
      Aboriginal children (aged 7.4-9.6 years) were sourced from the Lililwan Project.
      Fifty-eight per cent had a confirmed prenatal alcohol exposure and 13 (12%) met
      the Canadian 2005 criteria for FAS/partial FAS. Photographs were analysed using
      the FAS Facial Photographic Analysis Software to generate the mean PFL three
      point ABC-Score, five-point lip and philtrum ranks and four-point face rank in
      accordance with the 4-Digit Diagnostic Code. Intrarater and inter-rater
      reliability of digital ratings was examined in two assessors. Caucasian or
      African American racial norms for PFL and lip thickness were assessed for best
      fit; and agreement between digital and direct measurement methods was assessed.
      Results: Reliability of digital measures was substantial within (kappa: 0.70
      1.00) and between assessors (kappa: 0.64-0.89). Clinician and digital ratings
      showed moderate agreement (kappa: 0.47-0.58). Caucasian PFL norms and the African
      American Lip-Philtrum Guide 2 provided the best fit for this cohort. Conclusion:
      In an Aboriginal cohort with a high rate of FAS, assessment of facial
      dysmorphology using digital methods showed substantial inter- and intrarater
      reliability. Digital measurement of features has high reliability and until data
      are available from a larger population of Aboriginal children, the African
      American Lip-Philtrum Guide 2 and Caucasian (Stromland) PFL norms provide the
      best fit for Australian Aboriginal children.

PMID- 29637154
TI  - Epidemiological survey of mental health in adolescent school children of Gujarat,
      India.
AB  - Introduction: Mental health problems in adolescents are inadequately researched
      in low-resource settings. We aimed in this study to assess the prevalence of
      mental health problems and correlates in school children aged 13-17 years and
      compare differences between urban and rural schools in Anand District, Gujarat.
      Methods and analysis: A cross-sectional study was conducted in five Gujarati
      medium higher secondary schools in Anand, Gujarat. Six hundred and ninety-three
      students with equal distribution of boys and girls belonging to 9th to 12th
      grades were included in the study. Strengths and Difficulties Questionnaire (SDQ)
      was used to assess the mental health status of the students, and total
      difficulties scoring was used to categorise participants into normal (0-15) and
      high (borderline (16-19) and abnormal (20-40)). Socio-demographic data and
      Teenage Screening Questionnaire-Trivandrum (TSQ) were used to assess associated
      medical and psychosocial factors. Clearance was obtained from the institutional
      ethics committee before conducting the study. Results: 15% participants had a
      high SDQ score. Girls had more emotional problems, while the rest of the mental
      health problems were more prevalent in boys. Rural children were found to have
      more mental health issues. Having an eye problem, scoring <50% in last annual
      examinations, failure in examinations, difficulties in studying at home and
      difficulties in relationships were associated with high SDQ score. Keeping
      physically fit and having friends were associated with normal SDQ score. Logistic
      regression model revealed that age, receiving punishment in form of more homework
      and difficulty discussing friends with parents increased odds of high SDQ score,
      while having friends and after-school entertainment like watching movies
      decreased odds of high SDQ score. Conclusions: At least one in eight adolescents
      in this study was at risk of mental health problems. SDQ self-report
      questionnaire and TSQ survey may be used as a screening modality to identify at
      risk students.

PMID- 29637155
TI  - Oral paracetamol versus oral ibuprofen for closure of haemodynamically
      significant patent ductus arteriosus in preterm neonates (<32 weeks): a blinded,
      randomised, active-controlled, non-inferiority trial.
AB  - Introduction: Haemodynamically significant patent ductus arteriosus (hsPDA) is a
      common cause of mortality and morbidity in preterm infants. Existing medical
      therapies with ibuprofen or indomethacin have multiple adverse effects. Hence, an
      alternative drug like paracetamol given through oral route with less side effects
      need to be tested in an appropriate study design with least risk of bias to
      arrive at a conclusion. Methods and analysis: Multisite, randomised, active
      controlled, non-inferiority design. The primary objective is to study the
      efficacy of oral paracetamol for closure of hsPDA in comparison to oral ibuprofen
      in preterm neonates of <32 weeks' gestation. Randomisation web-based and
      allocation concealment would be done; the treating team, investigators, outcome
      assessors and laboratory personnel would be blinded from the intervention.
      Echocardiography images would be coded for independent review. Closure of PDA by
      the end of last dose of study drug or earlier would be the study endpoint. A
      sample size of 196 neonates would be enrolled with a non-inferiority margin of
      15%. Both intention-to-treat and per-protocol analysis will be done to assess the
      effect of contamination and protocol violations in the primary outcome. Ethics
      and dissemination: The trial would follow international code of ethics for
      clinical trial. The trial protocol was approved by the Institute Ethics Committee
      of all three centres. All serious adverse events would be reported in detail to
      the Institute Ethics Committee. A written informed consent would be obtained from
      one of the parents. No plan has been made for dissemination. Trial registration
      number: CTRI/2014/08/004805.

PMID- 29637156
TI  - Educational intervention to improve intravenous cannulation skills in paediatric
      nurses using low-fidelity simulation: Indian experience.
AB  - Introduction: Inserting, monitoring and maintaining intravenous access are
      essential components of nursing. We evaluated simulation training on a manikin to
      improve cannulation skills. Methods: Nursing staff managing paediatric patients
      were asked to cannulate NITA Newborn-1800 manikin before and after appropriate
      training. Skills were assessed by a single assessor using an objective structured
      clinical examination (OSCE) checklist. Four steps were identified as critical. A
      score of 8/10 (80%) was considered satisfactory. Knowledge was assessed by 10
      questions. A training module consisting of theoretical aspects, PowerPoint
      presentations, videos and hands on training over a manikin was conducted. Post
      training assessment was done 1 week later. Results: Seventy-five (80.6%) nurses
      who completed preassessments and postassessments were assessed for paired
      comparisons of knowledge and skill. The majority of the nurses were females, had
      contractual appointment, were in their early career phase and from the paediatric
      wards. The mean (SD) post-training knowledge score was greater vis-a-vis
      pretraining score (7.52 (1.58) vs 5.32 (1.57), P<0.001). A similar result was
      observed for total OSCE scores (9.22 (0.66) vs 7.91 (1.11), P<0.001).
      Significantly higher proportion of participants exhibited intravenous cannulation
      satisfactorily after the training vis-a-vis pretraining assessment (69 (92%) vs
      36 (48%), P<0.001). Conclusion: Training using manikin showed improvement in post
      training score of intravenous cannulation skill of paediatric nurses; however,
      this finding needs further confirmation by a randomised control trial, as our
      study does not have a control group.

PMID- 29637157
TI  - Influence of health insurance status on paediatric non-Hodgkin's lymphoma
      treatment in Kenya.
AB  - Objective: Non-Hodgkin's lymphoma (NHL) is the most common childhood malignancy
      in sub-Saharan Africa. Survival rates for NHL are higher than 80% in high-income
      countries.This study explores treatment outcomes of children with NHL in Kenya, a
      sub-Saharan low-income country, and the association between health insurance
      status at diagnosis and treatment outcomes. Design: This was a retrospective
      medical records study. All children diagnosed with NHL in 2010, 2011 and 2012
      were included. Data on treatment outcomes and health insurance status at
      diagnosis were collected. Results: Of all 63 patients with NHL, 35% abandoned
      treatment, 22% had progressive or relapsed disease, 14% died and 29% had event
      free survival. Most patients (73%) had no health insurance at diagnosis.
      Treatment outcomes in children with or without health insurance at diagnosis
      differed significantly (p=0.005). The most likely treatment outcome in children
      with health insurance at diagnosis was event-free survival (53%), whereas in
      children without health insurance at diagnosis it was abandonment of treatment
      (44%). Crude HR for treatment failure was 3.1 (95% CI 1.41 to 6.60, p=0.005) for
      uninsured versus insured children. The event-free survival estimate was
      significantly higher in children with health insurance at diagnosis than in
      patients without health insurance at diagnosis (p=0.003). Stage of disease at
      diagnosis was identified as a confounder of this association (adjusted HR=2.4,
      95% CI 0.95 to 6.12, p=0.063). Conclusions: Survival of children with NHL in
      Kenya is much lower compared with high-income countries. Abandonment of treatment
      is the most common cause of treatment failure. Health insurance at diagnosis was
      associated with better treatment outcomes and survival.

PMID- 29637158
TI  - Development of a core outcome set to determine the overall treatment success of
      acute uncomplicated appendicitis in children: a study protocol.
AB  - Introduction: In recent years, there has been growing interest in alternatives to
      appendicectomy. In particular, non-operative treatment of appendicitis, with
      antibiotics alone, has been proposed as a potential treatment. A small number of
      randomised controlled trials (RCTs) in adults and, more recently, children
      suggest that antibiotic treatment may be a valid alternative to appendicectomy.
      However, there is currently insufficient data to justify its widespread use.
      Prior to performing further efficacy studies of the treatment of appendicitis in
      children, it is imperative to identify the most relevant outcome measures for
      inclusion in the design of comparative studies. This is of particular importance
      when evaluating a novel treatment approach since the outcomes of importance may
      differ from those commonly reported with traditional therapies.A review of the
      relevant literature and electronic resources failed to identify a core outcome
      set (COS) for children with appendicitis. We aim to define a COS for the
      measurement of treatment interventions in children (<18 years) with acute
      appendicitis. Methods and analysis: This project will entail: (1) a systematic
      review to identify previously reported acute uncomplicated appendicitis treatment
      outcomes; (2) assembly of stakeholder panels (paediatric and adult surgeons,
      patients and parents); (3) a three-stage Delphi process; and (4) a final
      consensus meeting to complete the COS. Ethics and registration: COS development
      is part of CONservative TReatment of Appendicitis in Children - a randomised
      controlled Trial (Feasibility) (CONTRACT) study, for which full ethical approval
      for CONTRACT has been granted. The COS development study is registered with the
      COMET Initiative in May 2017 (http://www.comet
      initiative.org/studies/details/987).

PMID- 29637160
TI  - Paediatric clinical ethics in Australia and New Zealand: a survey.
AB  - Objectives: To quantify the presence, purpose, function, governance and funding
      of clinical ethics services (CES) in tertiary paediatric hospitals in Australia
      and New Zealand. Design setting and participants: A descriptive, quantitative
      survey was conducted across eight paediatric hospitals. Main outcome measures:
      Responses from survey questions on the presence, purpose, function, governance
      and funding of the CES. Results: Seven of eight tertiary paediatric hospitals
      identified access to CES. Regarding purpose and function, all CES provided
      clinical case consultation, six of seven provided education and training, six of
      seven assisted with organisational policy and guideline development and four of
      seven undertook original ethics research. There was wide variation in how case
      consultations were conducted, reported and documented. With respect to governance
      and funding, all CES reported to their hospital executive and only one CES
      reported having a dedicated, although small, budget. Conclusions: Heterogeneity
      in the process of case consultation and CES policy content exists across the
      organisations studied. There is consistency with the broader values that underpin
      CES such as their multidisciplinary nature and level of training required for key
      staff. There is an apparent lack of formal budgetary support from health services
      for CES activities, with support derived mostly from staff who contribute their
      time in addition to their primary roles.

PMID- 29637159
TI  - Exploring pneumonia risk factors in Vietnamese infants: a survey of new mothers.
AB  - Objective: To understand the prevalence of pneumonia risk factors and perceived
      barriers to risk factor reduction among Vietnamese infants. Methods: We conducted
      a cross-sectional survey of mothers in the postnatal wards of Da Nang Hospital
      for Women and Children in central Vietnam from 10 February 2017 to 24 February
      2017. Results: Of 286 mothers surveyed, 259 (91%) initiated breast feeding and
      207 (72%) intended to continue exclusive breast feeding for 6 months. No mother
      smoked cigarettes, but 42% of fathers did. Mothers' decision not to smoke was
      motivated by concerns for their own health and that of their baby. Households
      rarely used wood or coal for cooking (6%). Mothers indicated near universal (99%)
      uptake of the National Expanded Program of Immunization vaccinations. Few (64;
      22%) mothers knew about the pneumococcal conjugate vaccine; 56/64 (88%) indicated
      that they would purchase it for their infants. Family members rarely influenced
      mothers' decisions about breast feeding or vaccination, except in two instances
      where fathers were concerned about vaccine-related adverse effects. Conclusion:
      Modifiable pneumonia risk factors were uncommon among newborn babies in central
      Vietnam, apart from paternal cigarette smoke exposure. Successful local
      implementation of the WHO Essential Newborn Care package as well as high levels
      of maternal education and decision autonomy was observed.

PMID- 29637161
TI  - Intubating extremely premature newborns: a randomised crossover simulation study.
AB  - Objective: Determine whether tracheal intubation of extremely low birthweight
      (ELBW) neonates is more successful with a size-0 or size-00 Miller laryngoscope
      blade. Design: Randomised crossover simulation study. Setting: Simulated neonatal
      intensive care unit environment. Study subjects: Neonatology physicians and nurse
      practitioners (n=55). Interventions: Subjects performed four intubations in
      succession on a high-fidelity ELBW manikin with size-0 Miller and size-00 Miller
      blades from two different manufacturers. The intubation sequence was randomised.
      Intubations were recorded and scored for time analysis. Subjects completed
      surveys about blade preferences before and after completing the series of
      intubations. Main outcome measures: Total laryngoscopy time and first attempt
      success in less than 30 s. Results: There was no difference in total laryngoscopy
      time (median 23.7 vs 20.6 s) or first attempt success in <30 s (67.3% vs 69.1%)
      between the size-0 and size-00 blades. Differences were noted between the same
      size blades made by different manufacturers. Among subjects expressing a prestudy
      blade size preference, there was no difference in laryngoscopy time or first
      attempt success between blades. Regardless of blade size, subjects were less
      successful with the first blade in the randomised sequence. Conclusions: Our
      findings support the Neonatal Resuscitation Program recommendation identifying
      the size-00 blade as optional equipment. Operators need to be aware of design
      variations between manufacturers and they may benefit from 'just-in-time'
      training with a manikin prior to intubating a live patient.

PMID- 29637162
TI  - Breastfeeding disruption during hospitalisation for bronchiolitis in children: a
      telephone survey.
AB  - Background: Hospitalisation for an acute bronchiolitis might lead to unwanted
      weaning off breast feeding for several reasons (respiratory distress, use of
      enteral or parenteral feeding, mothers tiredness, among others), yet it has never
      been really evaluated or quantified. Methods: We conducted this telephone survey
      to evaluate breastfeeding disruption during hospitalisation for bronchiolitis and
      try to identify its determining factors for future interventions. This cross
      sectional study extends over one epidemic season of bronchiolitis in a tertiary
      care hospital. All patients aged 6 months or younger hospitalised with acute
      bronchiolitis and receiving at least partial breast feeding were eligible for the
      study (n=144). Patients discharged home whose parents accepted to be contacted
      for a phone survey were included. Parents were contacted 3 months (range 0.5-6)
      after discharge. Results: Eighty-four patients were included in the study. Median
      length of hospital stay was 3 days (1; 34), and 27 patients spent some time in
      paediatric intensive care unit. Forty-three mothers stated that hospitalisation
      modified their breast feeding (17 stopped, 12 switched to partial breast feeding
      and 14 reduced without stopping). Mothers stated that the causes of breastfeeding
      disturbance were lack of support and advices (n=27) followed by child's
      respiratory disease (n=14), logistic hospital difficulties (n=13) and personal
      organisation issues (n=4). Conclusion: Admission to hospital with bronchiolitis
      may adversely affect breast feeding. Correct advices and support could be a
      determining factor, and further studies should focus on preventive interventions.

PMID- 29637163
TI  - Hyperglycaemic preterm neonates exhibit insulin resistance and low insulin
      production.
AB  - Objectives: To explore and compare the relationships between postmenstrual age
      (PMA), insulin, C-peptide and blood glucose concentrations (BGC) in
      hyperglycaemic and euglycaemic preterm neonates (PMA <30 weeks). Design:
      Observational. Setting: Dunedin Hospital Neonatal Intensive Care Unit, New
      Zealand. Patients: Preterm neonates were recruited and included nine insulin
      treated hyperglycaemic and 20 euglycaemic neonates. Samples for euglycaemic
      neonates were obtained from leftover blood, and for insulin-treated neonates,
      additional blood was collected at the same time as the patients' routine 4 hourly
      blood glucose test over a 24-hour period (six samples). Main outcome measures:
      Blood samples were collected, plasma was analysed for insulin and C-peptide and
      was measured in temporal association with BGC. Results: The euglycaemic neonates
      had a mean PMA (SD) of 28 (1.4) weeks and the insulin-treated neonates had 25.5
      (1.8) weeks. C-peptide plasma concentrations were significantly lower (p<0.01) in
      the insulin-treated hyperglycaemic neonates (51.7 (100) pmol/L; 200(208) pmol/L)
      indicating lower insulin production. Insulin plasma concentrations (r=-0.38), BGC
      (r=-0.38), C-peptide plasma concentrations (r=0.36) and insulin/C-peptide ratios
      (r=-0.49) were all significantly affected by PMA (p<0.01). As expected, insulin
      plasma concentrations were higher in the insulin-treated hyperglycaemic neonates
      (156 (161) pmol/L; 93.2 (63.1) pmol/L, p<0.01) confirming that intravenous
      exogenous insulin reached these neonates. Conclusions: This study demonstrates
      that preterm neonates exhibit insulin resistance, hyperglycaemic neonates have
      lower insulin production than euglycaemic neonates and treatment with exogenous
      insulin did not appear to suppress insulin production in these neonates.

PMID- 29637164
TI  - Financial crises and child health: reflections from Iceland.

PMID- 29637165
TI  - Assessing the quality of paediatric antibiotic prescribing by community
      paediatricians: a database analysis of prescribing in Lombardy.
AB  - Objective: To evaluate the quality of paediatricians' antibiotic prescribing
      using administrative databases. Methods: The data source was the database of
      reimbursed prescriptions of the Lombardy Region, Italy. Children 1-13 years were
      included. An index prescription was defined as the first antibiotic prescription
      during a year period (2011) that occurred without previous, recent, antibiotic
      prescriptions or hospital or emergency department admissions. The A indicator was
      the percentage of children, cared for by paediatricians, receiving amoxicillin at
      the index prescription (minimum target 50%). The B indicator was the percentage
      of children receiving exclusively non-penicillin antibiotics in unrelated
      infection episodes (maximum target 10%). Indicators were evaluated for each
      prescriber and geographical area. Results: Overall 424 280 children (cared for by
      1164 paediatricians) received an index prescription and were included in the
      study. Amoxicillin alone was prescribed at the index prescription only to 23.6%
      of children (7.9%-46.3% within different areas of the region).The percentage of
      paediatricians who reached the target for the quality indicators was low (12.8% A
      indicator; 54.0% B indicator; 11.3% both). Almost half of the paediatricians
      (44.5%) showed inadequate quality of antibiotic prescribing, failing to reach the
      target for both indicators. Quality of prescribing was about four times worse in
      high prescribers and younger paediatricians. A geographical cluster of
      paediatricians reaching the target for both indicators was identified. These
      paediatricians had, for several years, previously been involved in educational
      programme. Conclusions: Quality of prescribing was generally unsatisfactory, but
      increased in a group of paediatricians previously involved in educational
      interventions and increased with increasing age. Further studies are warranted in
      order to validate these promising indicators as a benchmarking tool in other
      studies, when diagnosis is unknown.

PMID- 29637166
TI  - Investigating the roles and training of paediatric research nurses working across
      Europe: a questionnaire-based survey.
AB  - Background: The key role played by research nurses in coordinating clinical
      trials in a paediatric setting has developed in line with increasing complexities
      of trial design. A questionnaire-based survey was conducted to investigate the
      training of research nurses involved in paediatric trials across Europe, to
      identify potential training needs and compare roles across specialties and
      countries. Methods: A structured, cross-sectional questionnaire survey was used,
      with the aim of describing and quantifying research nurse experiences. The
      questionnaire was designed to cover four main areas of interest: demographics,
      training, clinical trial experience and research nurse roles/activities. Results:
      The questionnaire was completed by 341 respondents across 45 different
      specialties in 20 European countries. A higher percentage of research nurses
      within 3 years of taking up post were dissatisfied with the level of training
      received (16%), as compared with those in post for 3-6 years (8%) and >6 years
      (6%). There was a trend towards a higher percentage of respondents receiving self
      funded training in mainland Europe, with reported values of 15%-20%, as compared
      with <5% in the UK and Ireland. Only 3% of research nurses prescribed
      investigational medicinal products in a clinical trial setting, with contrasting
      roles observed between countries. Conclusions: While high levels of training
      satisfaction were observed, 67% of respondents felt they would benefit from
      additional training in line with frequently changing practices. Currently, low
      levels of nurse prescribing are observed in a paediatric clinical trial setting
      across Europe. Appropriate research nurse training programmes should be promoted
      through national networks across Europe.

PMID- 29637167
TI  - Improving case ascertainment of congenital anomalies: findings from a prospective
      birth cohort with detailed primary care record linkage.
AB  - Background: Congenital anomalies (CAs) are a common cause of infant death and
      disability. We linked children from a large birth cohort to a routine primary
      care database to detect CA diagnoses from birth to age 5 years. There could be
      evidence of underreporting by CA registries as they estimate that only 2% of CA
      registrations occur after age 1 year. Methods: CA cases were identified by
      linking children from a prospective birth cohort to primary care records. CAs
      were classified according to the European Surveillance of CA guidelines. We
      calculated rates of CAs by using a bodily system group for children aged 0 to <5
      years, together with risk ratios (RRs) with 95% CIs for maternal risk factors.
      Results: Routinely collected primary care data increased the ascertainment of
      children with CAs from 432.9 per 10 000 live births under 1 year to 620.6 per 10
      000 live births under 5 years. Consanguinity was a risk factor for Pakistani
      mothers (multivariable RR 1.87, 95% CI 1.46 to 2.83), and maternal age >34 years
      was a risk factor for mothers of other ethnicities (multivariable RR 2.19, 95% CI
      1.36 to 3.54). Education was associated with a lower risk (multivariable RR 0.78,
      95% CI 0.62 to 0.98). Conclusion: 98% of UK CA registrations relate to diagnoses
      made in the first year of life. Our data suggest that this leads to incomplete
      case ascertainment with a further 30% identified after age 1 year in our study.
      Risk factors for CAs identified up to age 1 year persist up to 5 years. National
      registries should consider using routine data linkage to provide more complete
      case ascertainment after infancy.

PMID- 29637168
TI  - Rare disease: a national survey of paediatricians' experiences and needs.
AB  - Objective: To describe the experiences of Australian paediatricians while caring
      for children with rare diseases, and their educational and resource needs.
      Design: A brief online survey was developed and deployed to a representative
      sample of 679 paediatricians from the Australian Paediatric Surveillance Unit
      database. Results: Of the 679 paediatricians, 242 (36%) completed the survey. The
      respondents were representative of all states and territories of Australia, urban
      and rural regions, and hospital and private practice. Almost all respondents
      (93%) had seen children with one or more of >350 different rare diseases during
      their career; 74% had seen a new patient with rare disease in the last 6 months.
      The most common problems encountered while caring for patients were: diagnostic
      delays (65%), lack of available treatments (40%), clinical guidelines (36%) and
      uncertainty where to refer for peer support (35%). Few paediatricians said that
      rare diseases were adequately covered during university (40%) or the Fellowship
      of the Royal Australasian College of Physicians (50%) training, and 28% felt
      unprepared to care for patients with rare diseases. Paediatricians wanted lists
      of specialist referral services (82%) and online educational modules about rare
      diseases (78%) that could be accessed via one online portal that consolidated
      multiple resources. Smartphone applications on rare diseases were favoured by
      paediatricians aged <50 years and by female paediatricians. Conclusions: An
      online educational portal should be developed and maintained for accuracy and
      currency of information to support dissemination of rare disease guidelines,
      referral pathways and coordination services relevant to Australian paediatricians
      and other health professionals who care for children with rare diseases.

PMID- 29637169
TI  - Poor inter-observer agreement in the measurement of respiratory rate in children:
      a prospective observational study.
AB  - Objective: To determine the inter-observer agreement of a respiratory rate (RR)
      count on a child when assessed by three independent observers. Design: The RR of
      169 children (age range: 3 days to 15 years) was measured by three independent
      observers over a 3-month period. The first RR was taken by different healthcare
      professionals (HCPs) from within the hospital using their own preferred method of
      measurement. A further count of RR was then taken by two observers from the
      research team simultaneously within 30 min of the first measurement, using the
      WHO-recommended method of measurement. Results: 507 RR measurements were taken on
      169 children. Median RR showed a 4 beats per minute (bpm) difference between the
      HCP (median RR 32 bpm) and the researchers (median RR 28 bpm). The 95% limits of
      agreement between the first measurement and second and third measurements were 
      10.2 to 17.7 bpm and -11.4 to 18.7 bpm, respectively. For simultaneous
      measurements, the 95% limits of agreement were -7.1 to 7.0 bpm. 81 children had a
      RR > 95th centile for their age and an even poorer level of agreement was seen in
      these children than in those whose RR was within normal range. In only 27 of
      these 81 children (33%) did all three observers agree on the presence of a raised
      RR. Conclusions: Inter-observer agreement for the measurement of RR in children
      is poor. The effect that this variation has on the clinical assessment and
      subsequent management of a child may be significant. These findings highlight the
      need for a robust review of our current measurement methods and interpretation of
      an important vital sign.

PMID- 29637170
TI  - Impact of hypoglycaemia on neurodevelopmental outcomes in hypoxic ischaemic
      encephalopathy: a retrospective cohort study.
AB  - Background: Low blood glucose levels (BGLs) in infants are known to adversely
      affect neurodevelopmental outcomes. However, this risk is not well explored in
      infants with hypoxic ischaemic encephalopathy (HIE) that receive therapeutic
      hypothermia (TH). Additionally, little information is available on the optimal
      BGLs to target in infants with HIE. Aim: To explore the association between
      hypoglycaemia and neurodevelopmental outcomes at different BGL thresholds (2.6
      and 3.0 mmol/L) in neonates with HIE treated with TH. Methods: Retrospective
      cohort study. Clinical information and 2-year neurodevelopmental data using
      Bayley Scales of Infant Development, third edition (BSID-III) and disabilities
      were recorded for infants born in Western Australia with HIE and treated with TH
      between February 2008 and February 2012. Multivariable logistic regression models
      explored the association between hypoglycaemia and neurodevelopmental outcomes.
      Results: 122 infants underwent a total of 1616 BGL estimations before and during
      72 hours of TH. Hypoglycaemia (BGL<2.6 mmol/L) occurred in 38/122 (31%) infants
      and 11/122 (9%) had recurrent hypoglycaemia (three or more episodes). Infants
      with recurrent hypoglycaemia (<2.6 mmol/L) had significantly lower mean BSID-III
      cognitive, language and socioemotional subscale scores. On multivariable
      analysis, recurrent hypoglycaemia (<2.6 mmol/L) was associated with increased
      odds of death or disability (adjusted OR 8.15; 95% CI 1.31 to 50.58; p=0.024).
      Recurrent hypoglycaemia (<3.0 mmol/L) during the first 12 hours of life was also
      associated with severe disability among survivors (adjusted OR 11.13; 95% CI 2.06
      to 59.89; p=0.005). Conclusions: Early recurrent hypoglycaemia was associated
      with increased risk of death or severe disability in neonates undergoing TH for
      HIE. Prospective studies are needed to identify the ideal target BGL in this
      population.

PMID- 29637171
TI  - Probiotics, prematurity and neurodevelopment: follow-up of a randomised trial.
AB  - Objective: To determine the impact of one probiotics combination on the
      neurodevelopment of very preterm children at 2-5 years corrected gestational age
      (CA). Design: Follow-up study of survivors of a double-blinded, placebo
      controlled, randomised trial of probiotic effects on late-onset sepsis in very
      preterm infants that found reduced necrotising enterocolitis. Setting: 10
      tertiary perinatal centres in Australia and New Zealand. Patients: 1099 very
      preterm infants born <32 weeks' gestation and weighing <1500 g. Intervention:
      Probiotics (Bifidobacterium infantis, Streptococcus thermophilus and
      Bifidobacterium lactis) or placebo administered from birth until discharge home
      or term CA, whichever came sooner. Main outcome measures: Major
      neurodevelopmental impairment comprised any of moderate/severe cerebral palsy
      (Gross Motor Function Classification System score 2-5), motor impairment (Bayley
      III Motor Composite Scale <-2SD or Movement Assessment Battery for Children <15th
      centile if >42 months' CA), cognitive impairment (Bayley-III Composite Cognitive
      or Language Scales <-2SD or Wechsler Preschool and Primary Scale of Intelligence
      Full Scale Intelligence Quotient <-2SD if >42 months' CA), blindness or deafness.
      Results: Outcome data were available for 735 (67%) participants, with 71 deaths
      and 664/1028 survivors assessed at a mean age of 30 months. Survival free of
      major neurodevelopmental impairment was comparable between groups (probiotics 281
      (75.3%) vs placebo 271 (74.9%); relative risk 1.01 (95% CI 0.93 to 1.09)). Rates
      of deafness were lower in probiotic-treated children (0.6% vs 3.4%). Conclusion:
      Administration of the probiotics combination Bifidobacterium infantis,
      Streptococcus thermophilus and Bifidobacterium lactis to very preterm babies from
      soon after birth until discharge home or term CA did not adversely affect
      neurodevelopment or behaviour in early childhood. Trial registration number:
      Australia and New Zealand Clinical Trials Register (ANZCTR):
      ACTRN012607000144415.

PMID- 29637173
TI  - Fortune favours the brave: composite first-person narrative of adolescents with
      congenital heart disease.
AB  - Background: An interdisciplinary framework including a narrative element could
      allow addressing lack of awareness or excessive anxieties and teasing out
      divergences between patients' health status and their expectations. This could be
      particularly relevant for adolescents with congenital heart disease (CHD).
      Objective: To develop a collective narrative ensuing from a creative activity
      involving adolescents with CHD, in order to explore their health perceptions and
      expectations. Design: Artist-led workshop process supported by a
      multidisciplinary team. Setting and participants: Young people with CHD (n=5, age
      17-18 years, two men) were involved in the creative process, which encouraged
      them, over two sessions, to elaborate imagery relating to their uniqueness as
      individuals and their hearts. On top of creative activities (including self
      portraits, embossing, body mapping and creative writing), participants were also
      shown their hearts in the form of cardiovascular MRIs and three-dimensional (3D)
      models manufactured by means of 3D printing. Methods: A composite first-person
      narrative approach was adopted to handle the emerged phenomenological
      descriptions and creative outputs, in order to shape a unified story. Results:
      The composite first-person narrative highlighted themes central to the patients,
      including their interpretation of medical references, their resilience and their
      awareness of anatomical complexity. Discussion and conclusions: Exploring the
      narrative of adolescents with CHD can offer unique insight into the way they view
      their hearts at a crucial stage of their care. An artist-led creative workshop
      supported by a multidisciplinary team can be a valuable approach to collect such
      narratives from patients and begin exploring them.

PMID- 29637172
TI  - Impact of neonatal resuscitation trainings on neonatal and perinatal mortality: a
      systematic review and meta-analysis.
AB  - Background: Training of birth attendants in neonatal resuscitation is likely to
      reduce birth asphyxia and neonatal mortality. We performed a systematic review
      and meta-analysis to assess the impact of neonatal resuscitation training (NRT)
      programme in reducing stillbirths, neonatal mortality, and perinatal mortality.
      Methods: We considered studies where any NRT was provided to healthcare personnel
      involved in delivery process and handling of newborns. We searched MEDLINE,
      CENTRAL, ERIC and other electronic databases. We also searched ongoing trials and
      bibliographies of the retrieved articles, and contacted experts for unpublished
      work. We undertook screening of studies and assessment of risk of bias in
      duplicates. We performed review according to Cochrane Handbook. We assessed the
      quality of evidence using the GRADE approach. Results: We included 20 trials with
      1 653 805 births in this meta-analysis. The meta-analysis of NRT versus control
      shows that NRT decreases the risk of all stillbirths by 21% (RR 0.79, 95% CI 0.44
      to 1.41), 7-day neonatal mortality by 47% (RR 0.53, 95% CI 0.38 to 0.73), 28-day
      neonatal mortality by 50% (RR 0.50, 95% CI 0.37 to 0.68) and perinatal mortality
      by 37% (RR 0.63, 95% CI 0.42 to 0.94). The meta-analysis of pre-NRT versus post
      NRT showed that post-NRT decreased the risk of all stillbirths by 12% (RR 0.88,
      95% CI 0.83 to 0.94), fresh stillbirths by 26% (RR 0.74, 95% CI 0.61 to 0.90), 1
      day neonatal mortality by 42% (RR 0.58, 95% CI 0.42 to 0.82), 7-day neonatal
      mortality by 18% (RR 0.82, 95% CI 0.73 to 0.93), 28-day neonatal mortality by 14%
      (RR 0.86, 95% CI 0.65 to 1.13) and perinatal mortality by 18% (RR 0.82, 95% CI
      0.74 to 0.91). Conclusions: Findings of this review show that implementation of
      NRT improves neonatal and perinatal mortality. Further good quality randomised
      controlled trials addressing the role of NRT for improving neonatal and perinatal
      outcomes may be warranted. Trial registration number: PROSPERO
      2016:CRD42016043668.

PMID- 29637174
TI  - Sex differences in child and adolescent physical morbidity: cohort study.
AB  - Background: Evidence on sex differences in physical morbidity in childhood and
      adolescence is based largely on studies employing single/few physical morbidity
      measures and different informants. We describe sex differences in a wide range of
      parent/carer-reported physical morbidity measures between ages 4 and 13 years to
      determine evidence for a generalised pattern of an emerging/increasing female
      'excess'. Methods: Parents/carers (approximately 90% mothers) of the population
      based UK ALSPAC cohort provided data on general health, physical
      conditions/symptoms and infections in their child approximately annually between
      ages 4 and 13. Logistic regression analyses determined the odds of each morbidity
      measure being reported in respect of females (vs males) at each age and the sex
      by-age interaction, to investigate any changing sex difference with age. Results:
      Six measures (general health past year/month, high temperature, rash, eye and ear
      infections) demonstrated an emerging female 'excess', and six (earache, stomach
      ache, headache, lice/scabies, cold sores, urinary infections) an increasing
      female 'excess'; one (breathlessness) showed a disappearing male 'excess'. Just
      two showed either an emerging or increasing male 'excess'. Most changes were
      evident during childhood (prepuberty). Six measures showed consistent female
      'excesses' and four consistent male 'excesses'. Few measures showed no sex
      differences throughout this period of childhood/early adolescence. Conclusion:
      Sex differences are evident for a wide range of parent-reported physical
      morbidity measures in childhood and early adolescence. Far more measures showed
      an emerging/increasing female 'excess' than an emerging/increasing male 'excess'.
      Further studies are required to examine whether patterns differ across
      sociodemographic/cultural groups, and to explain this generalised pattern.

PMID- 29637175
TI  - Early preterm nutrition and the urinary metabolome in young adult life: follow-up
      of a randomised controlled trial.
AB  - Objective: We aimed to test the hypothesis that early diet programmes the
      metabolic profile of young adults born preterm. Design: We analysed banked urine
      samples obtained at a 20-year follow-up visit from adults that had participated
      as neonates in controlled trials involving randomisation within 48 hours of birth
      to feeds of preterm formula (PTF), banked breast milk (BBM) or term formula (TF)
      for 1 month postnatally. Main outcome measures: We performed proton nuclear
      magnetic resonance spectroscopy, analysing spectra by dietary group and sex.
      Orthogonal projections to latent structure discriminant analyses was used to
      model class differences and identify metabolites contributing to the differences
      between groups. Additionally, spectra were correlated with birth weight,
      gestational age and weight z score at 2 weeks of age. Results: Of the original
      number of 926 trial participants, urine samples were available from 197 (21%)
      healthy young adults (42% men) born preterm (mean 30.7+/-2.8 weeks) and
      randomised to BBM (n=55; 28 men), TF (n=48; 14 men) and PTF (n=93; 40 men). We
      found no significant differences in urinary spectra between dietary groups
      including when stratified by sex. Correlation analysis revealed a weak
      association between metabolic profile and gestational age that was lost on
      controlling for ethanol excretion. Conclusions: We found no evidence that dietary
      exposures in the neonatal period influence the metabolic phenotype in young adult
      life.

PMID- 29637176
TI  - Resuscitating neonates: 65 years after Virginia Apgar.

PMID- 29637177
TI  - Prediction of outcomes of extremely low gestational age newborns in Australia and
      New Zealand.
AB  - Objective: To determine the accuracy of the National Institute of Child Health
      and Human Development (NICHD) calculator in predicting death and
      neurodevelopmental impairment in Australian and New Zealand infants. Design:
      Population-based cohort study. Setting: Australia and New Zealand. Patients:
      Preterm infants 22-25 completed weeks gestation. Interventions: Comparison of
      NICHD calculator predicted rates of death and death or neurodevelopmental
      impairment, with actual rates recorded in the Australian and New Zealand Neonatal
      Network cohort. Main outcome measures: Infant death and death or
      neurodevelopmental impairment rates. Results: A total of 714 infants were
      included in the study. Of these infants, 100 (14.0%) were <24 weeks, 389 (54.5%)
      male, 529 (74.1%) were singletons, 42 (5.9%) had intrauterine growth restriction,
      563 (78.9%) received antenatal steroids and 625 (87.5 %) were born in a tertiary
      hospital. There were 288 deaths (40.3%), 75 infants (10.5%) with neurodevelopment
      impairment and 363 (50.8%) with death or neurodevelopmental impairment. The area
      under the curve (AUC) for prediction of death and the composite death or
      neurodevelopmental impairment by the NICHD calculator in our population was
      0.65(95% CI 0.61 to 0.69) and 0.65 (95% CI 0.61 to 0.69), respectively. When
      stratified and compared with gestational age outcomes, the AUC did not change
      substantially for the outcomes investigated. The calculator was less accurate
      with outcome predictions at the extreme categories of predicted outcomes
      underestimation of outcomes for those predicted to have the lowest risk (<20%)
      and overestimation for those in the highest risk category (>80%). Conclusion: In
      our recent cohort of extremely preterm infants, the NICHD model does not
      accurately predict outcomes and is marginally better than gestational age based
      outcomes.

PMID- 29637178
TI  - Preterm infant outcomes in relation to the gestational age of onset and duration
      of prelabour rupture of membranes: a retrospective cohort study.
AB  - Objective: To determine the hospital outcomes of liveborn infants at 23-31 weeks
      following prelabour preterm rupture of membranes (PPROM). Method: A regional
      retrospective cohort study of 4454 infants of 23-31 weeks' gestation admitted to
      a tertiary neonatal network between 2007 and 2011. Primary outcome was the
      composite chronic lung disease (CLD) or mortality at discharge. Results: 225 (5%)
      neonates had a history of PPROM occurring prior to 24+0 weeks (Early-PPROM), 829
      (19%) had a history of PPROM at or after 24+0 weeks' gestation (Late-PPROM) and
      3400 (76%) had no history of PPROM (No-PPROM). In comparison to No-PPROM, Early
      PPROM group had higher CLD/mortality in infants born at 23-27 weeks (OR 1.95; 95%
      CI 1.34 to 2.85) and 28-31 weeks (OR 4.98; 95% CI 2.99 to 8.28). Within Early
      PPROM group, the latency of PPROM >14 days had lower CLD/mortality in comparison
      to latency <=14 days (57.6% vs 77%, OR 0.40; 95% CI 0.21 to 0.76). Late-PPROM
      group had significantly lower CLD/mortality in comparison to No-PPROM group at 23
      27 weeks (OR 0.50; 95% CI 0.37 to 0.69) and 28-31 weeks (OR 0.50; 95% CI 0.36 to
      0.71). Within Late-PPROM group, latency >14 days was associated with an increased
      CLD/mortality in 28-31 weeks (14.1% vs 5.4%, OR 2.88; 95% CI 1.31 to 6.38).
      Conclusions: Early-PPROM prior to 24 weeks' gestation had high incidence of
      CLD/mortality even after correcting for gestational age. Late-PPROM at or after
      24 weeks had lower CLD/mortality compared with No-PPROM. Latency >14 days in Late
      PPROM group at 28-31 week group increased the odds of CLD/mortality.

PMID- 29637179
TI  - Associations between birth at, or after, 41 weeks gestation and perinatal
      encephalopathy: a cohort study.
AB  - Background: Preterm birth causes long-term problems, even for infants born 1 or 2
      weeks early. However, less is known about infants born after their due date and
      over a quarter of infants are born over 1 week late, and many still remain
      undelivered after 2 weeks. The aim of this work is to quantify the risks of
      infants developing encephalopathy when birth occurs after the due date, and if
      other proposed risk factors modify this relationship. Methods: The dataset
      contain information on 4 036 346 infants born in Sweden between 1973 and 2012.
      Exposure was defined as birth 7, or more, days after the infants' due date. The
      primary outcome was the development of neonatal encephalopathy (defined as
      seizures, encephalopathy or brain injury caused by asphyxia or with unspecified
      cause). Covariates were selected as presumed confounders a priori. Results: 28.4%
      infants were born 1 or more weeks after their due date. An infant's risk of being
      born with encephalopathy was higher in the post 41 weeks group in the unadjusted
      (OR 1.40 (95% CI 1.32 to 1.49)) and final model (OR 1.38 (95% CI 1.29 to 1.47)),
      with the relative odds of encephalopathy increasing by an estimated 20% per week
      after the due date, and modified by maternal age (P=0.022). Conclusions:
      Singleton infants born at, or after, 41 weeks gestation have lower Apgar scores
      and higher risk of developing encephalopathy in the newborn period, and the
      association appeared more marked in older mothers. These data could be useful if
      provided to women as part of their decision-making.

PMID- 29637180
TI  - Public health approaches to safer cycling for children based on developmental and
      physiological readiness: implications for practice.
AB  - Introduction: Cyclists have a high mortality and morbidity per mile travelled
      compared with car occupants, a figure that is likely to increase if campaigns to
      increase active travel are successful. Concerns about safety is the leading
      factor limiting cycling for children. Objective: This review brings together a
      paediatric perspective based on the developmental readiness of children and young
      people and a public health approach to reducing injuries, to produce a practical
      agenda for improving the safety of cycling for children. Method: Selective
      literature review. Results: While most sports realise the importance of practice
      and training to create mastery of the game, similar thinking has not been
      consistently applied to cycling proficiency, so many children do not have an
      opportunity to master cycling before riding on the roads. Conclusions: The aim
      should be to minimise road traffic injuries involving children and young people
      in ways that create cobenefits for other members of society, increasing
      opportunities for active travel, reducing air pollution, creating more green
      space to play and reducing dependence on motor vehicles.Changes in legislation
      are required now to enable younger children to cycle on pavements while learning
      to ride and improvements in road design to separate cyclists from motor vehicles
      especially routes to school for older children.

PMID- 29637182
TI  - Is it appropriate to use WHO Multicentre Growth Reference Study standards to
      assess the growth parameters of Sri Lankan babies? A single-centre cross
      sectional study.
AB  - Objective: To compare the anthropometric measurements of newborns in a tertiary
      care hospital in Sri Lanka, with WHO standards. Methods: Birth weight, length and
      occipitofrontal circumference (OFC) of 400 consecutive, term newborns of healthy
      mothers were measured in a tertiary care hospital. Results: 400 subjects were
      approached and seven were excluded, concluding the study population to 184 boys
      and 209 females. Medians of birth weight, length and OFC were 3000 g, 49.95 cm
      and 34.15 cm of males and IQRs were 555.00, 2.70 and 1.70, respectively. For
      females, the medians of birth weight, length and OFC were 2900 g, 48.9 cm and
      34.00 cm with IQRs of 450.00, 2.70 and 1.50, respectively. The two-tailed t-test
      revealed that median weights of males (t=9.632) and females (t=12.04) and OFC of
      males (t=3.98) were significantly lower than the WHO medians. There was a
      significant association of birth weight, with mother's prepregnancy weight, in
      males (beta coefficient=12.629 with 95% CI 6.275 to 18.982) and females (beta
      coefficient=5.880, 95% CI 1.434 to 10.325). Significant associations of length
      (beta coefficient=0.046, 95% CI 0.012 to 0.080) and OFC (beta coefficient=0.033,
      95% CI 0.014 to 0.053) with mother's prepregnancy weight in males and length
      (beta coefficient=0.084, 95% CI 0.022 to 0.145) and weight (beta
      coefficient=10.780, 95% CI 0.93 to 20.629) with maternal age in females were
      found. Furthermore, birth weight in males was significantly associated with
      maternal height (beta coefficient=10.899, 95% CI 0.552 to 21.247). Education
      level, ethnicity and parity showed no significant associations with above
      parameters. Conclusion: The median weights of both sexes and OFC in males were
      significantly lower than the WHO standards. Island-wide studies are indicated to
      evaluate the appropriateness of applying WHO standards to Sri Lankan newborns.

PMID- 29637181
TI  - Bronchopulmonary dysplasia-impact of severity and timing of diagnosis on
      neurodevelopment of preterm infants: a retrospective cohort study.
AB  - Objective: To assess the contribution of the severity of bronchopulmonary
      dysplasia (BPD) and the time point of its diagnosis to the prediction of
      neurodevelopmental impairment (NDI) at corrected age of 2 years in preterm
      infants. Design: Retrospective cohort study. Setting: Level-III perinatal centre.
      Patients and outcome measures: Infants born in 2000-2013 with gestational age <30
      weeks. BPD was defined as FiO2 >21% for >=28 days and its severity classified as
      mild, FiO2=21%; moderate, FiO2 <30% and severe, FiO2 >=30% and/or positive
      pressure support. We applied these criteria at two time points: 36 and 40 weeks'
      postmenstrual age (PMA). Multivariable regression models were used to estimate
      the association (OR (95% CI)) between BPD characteristics and NDI defined as
      cognitive or motor development score <2 SD; severe cerebral palsy; deafness and
      blindness. Results: Of 610 (81% of cohort) children assessed at 2 years, 357
      (58%) had BPD and 98 (16%) had NDI. Neither FiO2 >21% for >=28 days nor mild or
      moderate BPD at either 36 or 40 weeks' PMA was associated with NDI, but severe
      BPD was (at 36 weeks' PMA 5.6 (2.0 to 16.0) and at 40 weeks' PMA 16.6 (4.6 to
      59.9)). Infants with severe BPD at both 36 and 40 weeks' PMA had lower mental
      (mean difference -11.4 (-18.5 to -4.3), -25.7(-35.9 to -15.5), respectively) and
      motor (-7.8 (-14.9 to -0.6), -20.1(-30.7 to -9.5), respectively), developmental
      scores than infants without BPD. Conclusion: In this cohort, severe BPD was a
      better independent predictor of NDI at 2 years than mild or moderate BPD. BPD
      diagnosed at 40 weeks' PMA might allow better identification of infants at
      highest risk for NDI.

PMID- 29637183
TI  - Who perpetrates violence against children? A systematic analysis of age-specific
      and sex-specific data.
AB  - Objective: The epidemiology of violence against children is likely to differ
      substantially by sex and age of the victim and the perpetrator. Thus far,
      investment in effective prevention strategies has been hindered by lack of
      clarity in the burden of childhood violence across these dimensions. We produced
      the first age-specific and sex-specific prevalence estimates by perpetrator type
      for physical, sexual and emotional violence against children globally. Design: We
      used random effects meta-regression to estimate prevalence. Estimates were
      adjusted for relevant quality covariates, variation in definitions of violence
      and weighted by region-specific, age-specific and sex-specific population data to
      ensure estimates reflect country population structures. Data sources: Secondary
      data from 600 population or school-based representative datasets and 43
      publications obtained via systematic literature review, representing 13 830
      estimates from 171 countries. Eligibility criteria for selecting studies:
      Estimates for recent violence against children aged 0-19 were included. Results:
      The most common perpetrators of physical and emotional violence for both boys and
      girls across a range of ages are household members, with prevalence often
      surpassing 50%, followed by student peers. Children reported experiencing more
      emotional than physical violence from both household members and students. The
      most common perpetrators of sexual violence against girls aged 15-19 years are
      intimate partners; however, few data on other perpetrators of sexual violence
      against children are systematically collected internationally. Few age-specific
      and sex-specific data are available on violence perpetration by schoolteachers;
      however, existing data indicate high prevalence of physical violence from
      teachers towards students. Data from other authority figures, strangers, siblings
      and other adults are limited, as are data on neglect of children. Conclusions:
      Without further investment in data generation on violence exposure from multiple
      perpetrators for boys and girls of all ages, progress towards Sustainable
      Development Goals 4, 5 and 16 may be slow. Despite data gaps, evidence shows
      violence from household members, peers in school and for girls, from intimate
      partners, should be prioritised for prevention. Trial registration number:
      PROSPERO 2015: CRD42015024315.

PMID- 29637184
TI  - Incidence of infantile Pompe disease in the Maroon population of French Guiana.
AB  - Objectives: The aim of this study was to describe the epidemiology of infantile
      Pompe disease (IPD) in French Guiana, a French overseas territory, by combining a
      retrospective case records study and a prospective anonymous genotyping in a
      sample of mothers followed in the two major maternity units of French Guiana.
      Methods: We identified 19 newborns with IPD born within a 13-year-period in
      French Guiana, corresponding to 1/4528 births. All children were born within the
      African-American Maroon (Bushinengue) community originating from slaves who
      settled along the Maroni river in the 19th century. We also performed an
      anonymised screening for all women in postpartum, in the two main maternity units
      of French Guiana. Results: Genetic investigations revealed that all patients with
      IPD were homozygotes or compound heterozygotes for two known pathogenic
      variations: c.2560C>T p.(Arg854*) that has already been reported in African
      Americans and c.1942G>A p.(Gly648Ser), a rare previously considered to be
      variant. We identified no heterozygotes among 453 mothers of various ethnicities
      in Cayenne, but 15 heterozygotes among 425 mothers (1/27) in Saint-Laurent-du
      Maroni (95% CI 1/45 to 1/17), all from the Maroon community, which corresponds to
      an expected IPD incidence in Maroons of 1/1727 (95% CI 1/1156 to 1/8100).
      Conclusion: The incidence of IPD in the Maroon community is roughly 50 times
      higher than elsewhere in the world. The presence of only two different variants
      in all affected patients is compatible with a double founder effect in a
      relatively small population that has seldom mixed with other regional populations
      in the past and therefore has a reduced pool of genotypes.

PMID- 29637185
TI  - Thrombospondin-2 predicts response to treatment with intravenous immunoglobulin
      in children with Kawasaki disease.
AB  - Objective: To investigate the predictive value of thrombospondin-2 (TSP-2) in
      assessing the response to intravenous immunoglobulin (IVIG) in children with
      acute Kawasaki disease (KD). Methods: This was a cohort study with controls. 71
      children with KD were recruited as the case group, including IVIG non-responder
      (n=17) and IVIG responder (n=54), and healthy children (n=27) and febrile
      children (n=30) were used as control groups. ELISA was used to measure plasma TSP
      2 and TSP-1 levels. The rank-sum test was used to compare groups of non-normally
      distributed data. Predictive value was evaluated through the receiver operating
      characteristic (ROC) curve. Results: Compared with the control groups, the plasma
      TSP-2 levels in acute KD were significantly elevated (TSP-2: 31.00 (24.02, 39.28)
      vs 21.93 (17.00, 24.73) vs 16.23 (14.00, 19.64) ng/mL, P<0.001). The plasma TSP-2
      level in the IVIG non-responder was significantly higher than the responder group
      (37.58 (31.86, 43.98) vs 27.84 (21.88, 33.48) ng/mL, P=0.002). When using an ROC
      curve to analyse the predictive effect of TSP-2 on non-responsiveness to IVIG
      treatment, the area under the curve was 0.752 (0.630, 0.875) (P=0.002). When the
      cut-off value for TSP-2 was 31.50 ng/mL, the sensitivity was 82.35%, the
      specificity was 64.81%. Conclusion: The plasma TSP-2 level was elevated in acute
      KD and it might be a novel predictor for IVIG resistance, which could help guide
      clinicians to choose individualised initial therapeutic regimens.

PMID- 29637186
TI  - Content uniformity of quartered hydrocortisone tablets in comparison with mini
      tablets for paediatric dosing.
AB  - Objectives: Children requiring cortisol replacement therapy are often prescribed
      hydrocortisone doses of 2.5 mg, but as this is commercially unavailable 10 mg
      tablets, with functional break lines, are split commonly in an attempt to deliver
      the correct dose. This study aimed to determine the dose variation obtained from
      quartered hydrocortisone tablets when different operators performed the splitting
      procedure and to ascertain whether better uniformity could be attained from mini
      tablets as an alternative formulation. Methods: Hydrocortisone 10 mg tablets were
      quartered by four different operators using a standard pill splitter.
      Hydrocortisone 2.5 mg mini-tablets (3 mm diameter) were formulated using a wet
      granulation method and manufactured using a high-speed rotary press simulator.
      The weight and content uniformity of the quartered tablets and mini-tablets were
      assessed according to pharmacopoeial standards. The physical strength and
      dissolution profiles of the mini-tablets were also determined. Results: More than
      half of all quartered 10 mg tablets were outside of the +/-10% of the stated US
      Pharmacopoeia hydrocortisone content (mean 2.34 mg, SD 0.36, coefficient of
      variation (CV) 15.18%) and more than 40% of the quartered tablets were outside
      the European Pharmacopoeia weight variation. Robust mini-tablets (tensile
      strengths of >4 MPa) were produced successfully. The mini-tablets passed the
      pharmacopoeial weight and content uniformity requirements (mean 2.54 mg, SD 0.04,
      CV 1.72%) and drug release criteria during in vitro dissolution testing.
      Conclusion: This study confirmed that quartering 10 mg hydrocortisone tablets
      produces unacceptable dose variations and that it is feasible to produce 3 mm
      mini-tablets containing more accurate doses for paediatric patients.

PMID- 29637187
TI  - Patient safety vulnerabilities for children with intellectual disability in
      hospital: a systematic review and narrative synthesis.
AB  - Purpose: Adults and children with intellectual disability (ID) are vulnerable to
      preventable morbidity and mortality due to poor quality healthcare. While poor
      quality care has been commonly identified among children with ID, evidence of the
      patient safety outcomes for this group is lacking and therefore explored in this
      review. Data sources: Systematic searches of six electronic bibliographic
      research databases were undertaken from January 2000 to October 2017, in addition
      to hand searching. Study selection: Keywords, subject headings and MeSH terms
      relating to the experience of iatrogenic harm during hospitalisation for children
      with ID were used. Potentially relevant articles were screened against the
      eligibility criteria. Non-English language papers were excluded. Data extraction:
      Data regarding: author(s), publication year, country, sample, health service
      setting, study design, primary focus and main findings related to measures of
      quality and safety performance were extracted. Results of data synthesis: Sixteen
      studies met the inclusion criteria, with three themes emerging: the impact of the
      assumptions of healthcare workers (HCWs) about the child with ID on care quality
      and associated safety outcomes; reliance on parental presence during
      hospitalisation as a protective factor; and the need for HCWs to possess
      comprehensive understanding of the IDs experienced by children in their care, to
      scientifically deduce how hospitalisation may compromise their safety, care
      quality and treatment outcomes. Conclusion: When HCWs understand and are
      responsive to children's individual needs and their ID, they are better placed to
      adjust care delivery processes to improve care quality and safety during
      hospitalisation for children with ID.

PMID- 29637188
TI  - Direct bilirubin levels observed in prolonged neonatal jaundice: a retrospective
      cohort study.
AB  - Objective: Prolonged neonatal jaundice is common and usually benign; however,
      assessment of bilirubin fractions is recommended to determine the need for
      further assessment for congenital liver disease, particularly biliary atresia.
      The direct (conjugated) bilirubin thresholds currently used are variable and
      poorly evidenced. Hence, we aimed to delineate direct bilirubin levels in disease
      free neonates with prolonged jaundice. Methods: We performed a retrospective
      cohort analysis of split bilirubin levels, and subsequent follow-up, for all
      neonates initially assessed in our prolonged neonatal jaundice clinic over 2
      years. We plotted centile charts for total, direct and direct-total bilirubin
      ratio levels against age at sampling. The association was assessed using linear
      regression analysis. Results: Data were collected for 420 neonates (501 blood
      samples) across an age range of 10-70 days. No significant liver disease was
      found. For each day of older age, total bilirubin fell by 3.72 umol/L (95% CI
      2.46 to 5.00) and direct bilirubin fell by 0.39 umol/L (0.18 to 0.59). The ratio
      between the two did not change significantly (-0.0006 to +0.0034). The 95th
      centile for direct bilirubin was stable at ~25 umol/L. Direct-total bilirubin
      ratio was very variable with some 95th centiles >30%. Conclusions: In a
      clinically relevant population of disease-free neonates with prolonged jaundice
      both the total and the direct bilirubin decreased with age. The absolute direct
      bilirubin is more useful clinically than the direct-total bilirubin ratio. Our
      results support National Institute for Health and Care Excellence guidance that
      conjugated bilirubin >25 umol/L, or even more stringent criteria, constitutes an
      appropriate threshold for further investigation for neonatal liver disease.

PMID- 29637189
TI  - Changes in survival and neurodevelopmental outcomes of infants born at <25 weeks'
      gestation: a retrospective observational study in tertiary centres in Japan.
AB  - Objective: To evaluate changes in the outcomes of infants born at <25 weeks'
      gestation in the past decade. Design: Retrospective observational study.
      Settings: A multicentre database of the Neonatal Research Network, Japan.
      Patients: A total of 3318 infants born at 22-24 weeks' gestation between periods
      1 (2003-2007) and 2 (2008-2012) from 52 tertiary centres. Main outcome measures:
      We compared death and neurodevelopmental impairments (NDIs) at 3 years of age,
      including cerebral palsy (CP), visual impairments (VIs), hearing impairments
      (HIs) and the developmental quotient (DQ) of the Kyoto Scale of Psychological
      Development test <70, between two periods using multivariate logistic regression
      analyses adjusted for the centre, gender, multiple gestation, maternal age,
      caesarean delivery, antenatal steroid use, pregnancy-related hypertension,
      clinical chorioamnionitis, congenital anomalies and birth weight. Results: A
      total of 496/1479 infants (34%) in period 1 and 467/1839 (25%) in period 2 died
      by 3 years of age (adjusted OR 0.70, 95% CIs 0.59 to 0.83). Follow-up data were
      collected from 631 infants (64% of survivors) in period 1 and 832 (61% of
      survivors) in period 2. The proportions of CP with Gross Motor Function
      Classification System >=2, VI and HI in the infants evaluated were lower, while
      that of DQ <70 was higher in period 2 than in period 1. Using multiple
      imputations to account for missing data, death or NDI decreased from 54% in
      period 1 to 47% in period 2 (0.83, 0.71 to 0.97). Significant decreases were
      observed in death or CP (0.65, 0.55 to 0.76), death or VI (0.59, 0.50 to 0.69)
      and death or HI (0.69, 0.58 to 0.81), but not in death or DQ <70 (0.91, 0.78 to
      1.06). Conclusion: Along with improved survival, CP, VI and HI, but not cognitive
      impairments decreased in infants born at <25 weeks' gestation between the two
      periods examined in the last decade. Further strategies are needed to reduce
      cognitive impairments in these infants.

PMID- 29637190
TI  - Protocol for a double blind, randomised placebo-controlled trial using
      ondansetron to reduce vomiting in children receiving intranasal fentanyl and
      inhaled nitrous oxide for procedural sedation in the emergency department (the
      FON trial).
AB  - Introduction: Intranasal fentanyl and nitrous oxide (N2O) can be combined to
      create a non-parenteral procedural sedation regimen for children in the
      paediatric emergency department. This combination of intranasal fentanyl and N2O
      provides effective pain relief for more painful procedures, but is associated
      with a higher incidence of vomiting than N2O alone. Our aim is to assess whether
      ondansetron used preventatively reduces the incidence of vomiting associated with
      intranasal fentanyl and N2O for procedural sedation compared with placebo.
      Methods and analysis: This study is a double blind, randomised placebo-controlled
      superiority trial. This is a single-centre trial of 442 children aged 3-18 years
      presenting to a tertiary care Paediatric Emergency Department at the Royal
      Children's Hospital (RCH), Melbourne, Australia, requiring procedural sedation
      with intranasal fentanyl and N2O. After written consent, eligible participants
      are randomised to receive ondansetron or placebo along with intranasal fentanyl,
      30-60 min prior to N2O administration. The primary outcome is vomiting during or
      up to 1 hour after procedural sedation. Secondary outcomes include: number of
      vomits and retching during procedural sedation, vomiting 1-24 hours after
      procedural sedation, procedural sedation duration and associated adverse events,
      procedure abandonment, parental satisfaction and the value parents place on the
      prevention of vomiting. This trial will allow refinement of a non-parenteral
      sedation regimen for children requiring painful procedures. Ethics and
      dissemination: This study has ethics approval at the RCH, Melbourne, protocol
      number 36174. The results from this trial will be submitted to conferences and
      published in a peer-reviewed journal. Trial registration number: Australian New
      Zealand Clinical Trials Registry (ACTRN12616001213437).

PMID- 29637191
TI  - Neonatal outcomes of live-born term singletons in vertex presentation born to
      mothers with diabetes during pregnancy by mode of birth: a New South Wales
      population-based retrospective cohort study.
AB  - Objectives: To investigate the association between the mode of birth and adverse
      neonatal outcomes of macrosomic (birth weight >=4000 g) and non-macrosomic (birth
      weight <4000 g) live-born term singletons in vertex presentation (TSV) born to
      mothers with diabetes (pre-existing and gestational diabetes mellitus (GDM)).
      Design: A population-based retrospective cohort study. Setting: New South Wales,
      Australia. Patients: All live-born TSV born to mothers with diabetes from 2002 to
      2012. Intervention: Comparison of neonatal outcomes by mode of birth (prelabour
      caesarean section (CS) and planned vaginal birth resulted in intrapartum CS, non
      instrumental or instrumental vaginal birth). Main outcome measures: Five-minute
      Apgar score <7, admission to neonatal intensive care unit (NICU) or special care
      nursery (SCN) and the need for resuscitation. Results: Among the 48 882 TSV born
      to mothers with diabetes, prelabour CS was associated with a significant increase
      in the rate of admission to NICU/SCN compared with planned vaginal birth.For TSV
      born to mothers with pre-existing diabetes, compared with non-instrumental
      vaginal birth, instrumental vaginal birth was associated with increased odds of
      the need for resuscitation in macrosomic (adjusted ORs (AOR) 2.6; 95% CI (1.2 to
      7.5)) and non-macrosomic TSV (AOR 3.3; 95% CI (2.2 to 5.0)).For TSV born to
      mothers with GDM, intrapartum CS was associated with increased odds of the need
      for resuscitation compared with non-instrumental vaginal birth in non-macrosomic
      TSV (AOR 2.3; 95% CI (2.1 to 2.7)). Instrumental vaginal birth was associated
      with increased likelihood of requiring resuscitation compared with non
      instrumental vaginal birth for both macrosomic (AOR 2.3; 95% CI (1.7 to 3.1)) and
      non-macrosomic (AOR 2.5; 95% CI (2.2 to 2.9)) TSV. Conclusion: Pregnant women
      with diabetes, particularly those with suspected fetal macrosomia, need to be
      aware of the increased likelihood of adverse neonatal outcomes following
      instrumental vaginal birth and intrapartum CS when planning mode of birth.

PMID- 29637192
TI  - Societal costs of permanent childhood hearing loss at teen age: a cross-sectional
      cohort follow-up study of universal newborn hearing screening.
AB  - Objective: To investigate the effects in adolescence of bilateral permanent
      childhood hearing loss (PCHL) > 40 dB and of exposure to universal newborn
      hearing screening (UNHS) on societal costs accrued over the preceding 12 months.
      Design setting participants: An observational cohort study of a sample of 110
      adolescents aged 13-20 years, 73 with PCHL and 37 in a normally hearing
      comparison group (HCG) closely similar in respect of place and date of birth to
      those with PCHL, drawn from a 1992-1997 cohort of 157 000 births in Southern
      England, half of whom had been exposed to a UNHS programme. Intervention: Birth
      in periods with and without UNHS. Outcome measures: Resource use and costs in the
      preceding 12-month period, estimated from interview at a mean age of 16.9 years
      and review of medical records. Effects on costs were examined in regression
      models. Results: Mean total costs for participants with PCHL and the HCG were L15
      914 and L5883, respectively (difference L10 031, 95% CI L6460 to L13 603),
      primarily driven by a difference in educational costs. Compared with the HCG,
      additional mean costs associated with PCHL of moderate, severe and profound
      severity were L5916, L6605 and L18 437, respectively. The presence of PCHL and an
      additional medical condition (AMC) increased costs by L15 385 (95% CI L8532 to
      L22 238). An increase of one unit in receptive language z-score was associated
      with L1616 (95% CI L842 to L2389) lower costs. Birth during periods of UNHS was
      not associated with significantly lower overall costs (difference L3594, 95% CI 
      L2918 to L10 106). Conclusions: The societal cost of PCHL was greater with more
      severe losses and in the presence of AMC and was lower in children with superior
      language scores. There was no statistically significant reduction in costs
      associated with birth in periods with UNHS. Trial registration number:
      ISRCTN03307358, pre-results.

PMID- 29637193
TI  - Effect of the Fukushima earthquake on weight in early childhood: a retrospective
      analysis.
AB  - Objective: There have been no reports evaluating the physical growth in early
      childhood in Fukushima Prefecture after the Great East Japan Earthquake. We
      retrospectively investigated the health examination data in early childhood (aged
      0-3 years). Methods: We divided the affected children into respective groups
      according to the interval from the disaster to the time of health examination and
      age as follows: group I, birth to 3-4 months in boys (1.81 (range, 0-6 months))
      and girls (1.79 (range, 0-7 months)); group II, 3-4 months to 6-10 months in boys
      (6.37 (range, 3-9 months)) and girls (6.35 (range, 3-9 months)); group III, 6-10
      months and 18 months in boys (16.2 (range, 5-22 months)) and girls (16.9 (range,
      5-22 months)); and group IV, 18 months to 36-42 months in boys (21.0 (range, 18
      24 months)) and girls (21.0 (range, 18-24 months)). Using height and body mass
      index, the health status of each group was compared with that of unaffected
      controls (ie, children who experienced the disaster after their health
      examination at 36-42 months). Results: The change in body mass index between the
      health examinations at 18 months and 36-42 months was significantly increased in
      group I (95% CI: all boys, 0.192 to 0.276 vs -0.006 to 0.062, P<0.001 and all
      girls, 0.108 to 0.184 vs -0.109 to -0.035, P<0.001) and group II (95% CI: all
      boys, 0.071 to 0.141 vs -0.006 to 0.062, P=0.002 and all girls, -0.042 to 0.024
      vs -0.109 to -0.035, P=0.013). Conclusions: Children who were affected by the
      disaster in Fukushima Prefecture in early childhood were overweight. The use of
      pre-existing information, such as health examination data, was beneficial for
      investigating the physical growth of affected children.

PMID- 29637194
TI  - Early childhood risk factors for constipation and soiling at school age: an
      observational cohort study.
AB  - Objective: Constipation and soiling are common in childhood. This study examines
      the comorbidity between childhood constipation and soiling and early childhood
      risk factors for these problems. Design: The sample comprised 8435 participants
      from the Avon Longitudinal Study of Parents and Children with maternally reported
      measures of constipation (six time points between 4 and 10 years) and soiling
      (five time points between 4 and 9 years). We used latent class analysis to
      extract longitudinal patterns of constipation and soiling. We examined whether
      the latent classes are differentially associated with maternally reported risk
      factors in early childhood (stool consistency, breast feeding, socioeconomic
      background, gestation, birth weight, developmental level and age at initiation of
      toilet training) using multinomial logistic regression models. Results: We
      extracted four latent classes: 'normative' (74.5%: very low probability of
      constipation or soiling), 'constipation alone' (13.2%), 'soiling alone' (7.5%)
      and 'constipation with soiling' (4.8%). Hard stools at 21/2 years were associated
      with increased odds of constipation alone. Developmental delay at 18 months was
      associated soiling alone and constipation with soiling, but not constipation
      alone. We found limited evidence of associations with socioeconomic background
      and no evidence of associations with age at initiation of toilet training, breast
      feeding, gestational age or birth weight. Conclusion: Constipation alone was the
      most prevalent pattern in this cohort. Treatment for hard stools in early
      childhood is needed to prevent chronic constipation at school age. Constipation
      with soiling was less common than soiling alone. Further research is needed into
      the causes of non-retentive soiling.

PMID- 29637195
TI  - Systemic exertion intolerance disease diagnostic criteria applied on an
      adolescent chronic fatigue syndrome cohort: evaluation of subgroup differences
      and prognostic utility.
AB  - Objective: Existing case definitions for chronic fatigue syndrome (CFS) all have
      disputed validity. The present study investigates differences between adolescent
      patients with CFS who satisfy the systemic exertion intolerance disease (SEID)
      diagnostic criteria (SEID-positive) and those who do not satisfy the criteria
      (SEID-negative). Methods: 120 adolescent patients with CFS with a mean age of
      15.4 years (range 12-18 years) included in the NorCAPITAL project (ClinicalTrials
      ID: NCT01040429) were post-hoc subgrouped according to the SEID criteria based on
      a comprehensive questionnaire. The two subgroups were compared across baseline
      characteristics, as well as a wide range of cardiovascular, inflammatory,
      infectious, neuroendocrine and cognitive variables. Data from 30-week follow-up
      were used to investigate prognostic differences between SEID-positive and SEID
      negative patients. Results: A total of 45 patients with CFS were SEID-positive,
      69 were SEID-negative and 6 could not be classified. Despite the fact that
      clinically depressed patients were excluded in the NorCAPITAL project, the SEID
      positive group had significantly higher score on symptoms suggesting a mood
      disorder (Mood and Feelings Questionnaire): 23.2 vs 13.4, difference 9.19 (95% CI
      5.78 to 12.6). No other baseline characteristics showed any group differences.
      When accounting for multiple comparisons, there were no statistically significant
      differences between the groups regarding cardiovascular, inflammatory,
      infectious, neuroendocrine and cognitive variables. Steps per day and Chalder
      Fatigue Questionnaire at week 30 showed no differences between the groups.
      Conclusion: The findings question the discriminant and prognostic validity of the
      SEID diagnostic criteria in adolescent CFS, and suggest that the criteria tend to
      select patients with depressive symptoms.

PMID- 29637196
TI  - Interventions for reducing unplanned paediatric admissions: an observational
      study in one hospital.
AB  - Objective: Evidence on how best to intervene to improve paediatric acute care and
      therefore reduce unplanned hospital admissions is weak. We describe service
      evaluation work at one hospital to assess interventions at critical clinical and
      service decision points. Design: We conducted an observational study using
      routine daily-collected data (April 2009-December 2015) from a medium-sized
      district general hospital in south-west UK, using before-and-after comparisons of
      admissions-related data to evaluate two interventions implemented in April and
      November 2014, respectively: (1) an advice and guidance (A&G) phone line, where a
      senior paediatrician is available for general practitioners (GPs) and emergency
      department (ED) and (2) a Short Stay Paediatric Assessment Unit (SSPAU). We
      analysed data on all admitted children (<18 years) in the catchment area
      (population estimate 27 740 in 2015). Outcomes were GP-referred attendances, ward
      admissions, less than 1 day admissions and length of stay. Results: A&G phone
      line was associated with a reduction in the mean number of less than 1 day
      admissions per month (difference in means before and after intervention -16.6
      (95% CI -0.2 to -32.9)) and an increase in overall monthly bed-days (difference
      72.5 (95% CI 21.0 to 124.0)), but there was little evidence of a change in GP
      referred attendances or ward admissions. SSPAU was associated with a reduction in
      the mean number of monthly ward admissions (difference -34.6 (95% CI -21.3 to 
      48.0)) and less than 1 day admissions (difference in means -21.7 (95% CI -8.4 to 
      35.1)) and a reduction in the mean number of overall bed-days per month
      (difference -50.2 (95% CI -12.1 to -88.3)). Conclusions: Interventions for
      reducing time taken to senior clinician review may be effective in better
      managing paediatric acute care. Further work should explore results by age,
      condition and injury/illness status.

PMID- 29637197
TI  - Ultrasound-guided placement of long peripheral cannulas in children over the age
      of 10 years admitted to the emergency department: a pilot study.
AB  - Objectives: Most children admitted to the emergency department (ED) require
      peripheral venous access (PVA), which is often difficult to perform or is
      unsuccessful. Ultrasound guidance helps with the placement of peripheral short
      cannulas (SC), but it has a limited cannula duration and a high risk of
      developing complications. The aim of this study was to compare success rates,
      dwell times and complications of peripheral venous long cannulas (LCs) inserted
      under ultrasound guidance with those of SCs in children. Methods: We
      prospectively studied all children older than 10 years of age admitted to our
      paediatric ED requiring PVA for an expected therapy of more than 5 days. In
      children with difficult intravenous access (DIVA), after two unsuccessful
      attempts of 'blind' placement of SCs, LCs (20 G, 8 cm) were inserted in the deep
      veins of arms using ultrasound guidance and the direct Seldinger technique.
      Results: LC placement (n=20) was successful in 100% of the cases. LC dwell time
      was 9.2+/-6.0 days, and most catheters were electively removed because they were
      no longer indicated. SC (n=20) placement showed a shorter dwell time duration,
      3.2+/-2.1 days (p<0.0001), with complications occurring in 70% of the cases
      compared with 25% of cases in patients with LC (p=0.002). No local or major
      infectious complications were reported with LC placement. Conclusions: Ultrasound
      guided placement of LC was associated with a low risk of catheter failure and
      complications compared with the 'blind' placement of SC. LC placement may be
      considered a valid option in patients with DIVA requiring PVA in paediatric ED or
      in children who are candidates for infusion therapy expected to last longer than
      5 days.

PMID- 29637199
TI  - BiOnIC: A Catalog of User Interactions with Biomedical Ontologies.
AB  - BiOnIC is a catalog of aggregated statistics of user clicks, queries, and reuse
      counts for access to over 200 biomedical ontologies. BiOnIC also provides
      anonymized sequences of classes accessed by users over a period of four years. To
      generate the statistics, we processed the access logs of BioPortal, a large open
      biomedical ontology repository. We publish the BiOnIC data using DCAT and SKOS
      metadata standards. The BiOnIC catalog has a wide range of applicability, which
      we demonstrate through its use in three different types of applications. To our
      knowledge, this type of interaction data stemming from a real-world, large-scale
      application has not been published before. We expect that the catalog will become
      an important resource for researchers and developers in the Semantic Web
      community by providing novel insights into how ontologies are explored, queried
      and reused. The BiOnIC catalog may ultimately assist in the more informed
      development of intelligent user interfaces for semantic resources through
      interface customization, prediction of user browsing and querying behavior, and
      ontology summarization. The BiOnIC catalog is available at: http://onto
      apps.stanford.edu/bionic.

PMID- 29637200
TI  - Interrater agreement and reliability assessment of proximal caries detection
      tools in mixed dentition: An in-vivo study.
AB  - OBJECTIVE: This in-vivo study was performed to assess the interrater agreement
      and reliability of ICDAS (visual), transillumination, radiographic, and laser
      fluorescence proximal caries detection tools in between primary and adjacently
      erupted permanent molars. METHOD AND MATERIALS: This study was in accordance with
      Guidelines for Reporting Reliability and Agreement Studies. Two calibrated
      examiners assessed the nonobvious noncavitated apparently sound 100 interproximal
      sites using predefined criteria. Interrater agreement was analyzed as proportion
      of agreement. Interrater reliability assessment was performed using weighted
      kappa statistics and intraclass correlation coefficient. RESULTS: The maximum
      interrater agreement was projected with conventional bitewing radiography (97%),
      and the minimum with DIAGNOdent pen (84%), with significant difference (P < .001)
      in the proportion of agreement. All methods showed substantial interrater
      reliability, except fiber-optic transillumination. Maximum interrater reliability
      was noticed for ICDAS (International Caries Detection and Assessment System)
      method with a weighted kappa value of 0.80 (96% CI, 0.58 - 0.93) followed by
      conventional and digital bitewing radiography, with values of 0.74 (95% CI, 0.51 
      0.96) and 0.73 (95% CI, 0.43 - 0.92) respectively. CONCLUSION: ICDAS and
      bitewing radiography seem to be the most reliable methods, with a higher
      proportion of agreement between the examiners compared to the other methods
      addressed in this study for proximal caries detection.

PMID- 29637198
TI  - Hypothermia for encephalopathy in low-income and middle-income countries:
      feasibility of whole-body cooling using a low-cost servo-controlled device.
AB  - : Although therapeutic hypothermia (TH) is the standard of care for hypoxic
      ischaemic encephalopathy in high-income countries, the safety and efficacy of
      this therapy in low-income and middle-income countries (LMICs) is unknown. We
      aimed to describe the feasibility of TH using a low-cost servo-controlled cooling
      device and the short-term outcomes of the cooled babies in LMIC. Design: We
      recruited babies with moderate or severe hypoxic ischaemic encephalopathy (aged
      <6 hours) admitted to public sector tertiary neonatal units in India over a 28
      month period. We administered whole-body cooling (set core temperature 33.5
      degrees C) using a servo-controlled device for 72 hours, followed by passive
      rewarming. We collected the data on short-term neonatal outcomes prior to
      hospital discharge. Results: Eighty-two babies were included-61 (74%) had
      moderate and 21 (26%) had severe encephalopathy. Mean (SD) hypothermia cooling
      induction time was 1.7 hour (1.5) and the effective cooling time 95% (0.08). The
      mean (SD) hypothermia induction time was 1.7 hour (1.5 hour), core temperature
      during cooling was 33.4 degrees C (0.2), rewarming rate was 0.34 degrees C (0.16
      degrees C) per hour and the effective cooling time was 95% (8%). Twenty-five
      (51%) babies had gastric bleeds, 6 (12%) had pulmonary bleeds and 21 (27%) had
      meconium on delivery. Fifteen (18%) babies died before discharge from hospital.
      Heart rate more than 120 bpm during cooling (P=0.01) and gastric bleeds (P<0.001)
      were associated with neonatal mortality. Conclusions: The low-cost servo
      controlled cooling device maintained the core temperature well within the target
      range. Adequately powered clinical trials are required to establish the safety
      and efficacy of TH in LMICs. Clinical trial registration number: NCT01760629.

PMID- 29637201
TI  - Cage-like Ta@B complexes (n = 23-28, q = -1-+ 3) in 18-electron configurations
      with the highest coordination number of twenty-eight.
AB  - Inspired by recent observations of the highest coordination numbers of CN = 10 in
      planar wheel-type complexes in D10h Ta@B10- and CN = 20 in double-ring tubular
      species in D10d Ta@B20- and theoretical prediction of the smallest endohedral
      metalloborospherene D2 Ta@B22- (1) with CN = 22, we present herein the
      possibility of larger endohedral metalloborospherenes C2 Ta@B23 (2), C2 Ta@B24+
      (3), C2v Ta@B24- (4), C1 Ta@B25 (5), D2d Ta@B26+ (6), C2 Ta@B272+ (7), and C2
      Ta@B283+ (8) based on extensive first-principles theory investigations. These
      cage-like Ta@Bqn complexes with B6 pentagonal or B7 hexagonal pyramids on their
      surface turn out to be the global minima of the systems with CN = 23, 24, 24, 25,
      26, 27, and 28, respectively, unveiling the highest coordination number of CN =
      28 in spherical environments known in chemistry. Detailed bonding analyses show
      that 1-8 as superatoms conform to the 18-electron configuration with a universal
      sigma + pi double delocalization bonding pattern. They are effectively stabilized
      via spd-pi coordination interactions between the Ta center and etan-Bn ligand
      which match both geometrically and electronically. Such complexes may serve as
      embryos of novel metal-boride nanomaterials.

PMID- 29637202
TI  - Controllable CO2-responsiveness of O/W emulsions by varying the alkane carbon
      number of a tertiary amine.
AB  - A series of CO2-responsive oil-in-water (O/W) emulsions were prepared by
      introducing hydrophobic tertiary amines (TAs) with varying alkane carbon numbers
      (ACNs) into the emulsion stabilized by sodium dodecyl benzene sulfonate (SDBS).
      TAs are converted to bicarbonate salts upon bubbling of CO2, which can form ion
      pairs with SDBS via electrostatic interaction, and then disrupt the stability of
      the emulsion. The reversible switch can be triggered by the removal of CO2. The
      ACN of TA, the concentration of SDBS/TA, the bubbling time of CO2, and the number
      of cycles are taken into account in order to study the controllable mechanism of
      these CO2-responsive emulsions. Because of the improved miscibility with oil, the
      ion pairs with TAs of larger ACNs can much more easily adhere to the oil phase,
      and then speed up the rupture rate of the oil droplets. The corresponding
      demulsification process is tracked by studying the interfacial tension, the zeta
      potential of the droplets, and microscope snapshots of all the systems. The UV
      vis spectrophotometer analysis of the water phase and the 1H-nuclear magnetic
      resonance (1H NMR) test are further designed to comprehend the significance of
      ACNs and the solubility product of the formed ion pairs.

PMID- 29637203
TI  - RbSe3B2O9(OH) and CsSe3B2O9(OH): one dimensional boroselenite-based anionic
      frameworks with second harmonic generation properties.
AB  - Two new alkali boroselenites RbSe3B2O9(OH) and CsSe3B2O9(OH) have been
      synthesized by traditional solid-state reactions. Single-crystal X-ray
      diffraction study indicated that they are isostructural and adopt a new type of
      structure, which crystallizes in the noncentrosymmetric space group P212121.
      Optical diffuse reflectance spectrum studies emphasized that both are indirect
      optical transitions with values of 3.79 and 4.17 eV for RbSe3B2O9(OH) and
      CsSe3B2O9(OH), respectively. Optical analysis revealed a broad transparency
      window in the 0.3-8.5 MUm region for both compounds. In addition, RbSe3B2O9(OH)
      featured a relatively weak second-harmonic-generation response, and for
      CsSe3B2O9(OH), the response is 0.8-times that of KH2PO4. Theoretical calculations
      of band structure, density of state, and linear and nonlinear optical properties
      were also performed to get insight into the relationships between electronic
      structures and their optical properties.

PMID- 29637204
TI  - Sulfur-functionalized three-dimensional graphene monoliths as high-performance
      anodes for ultrafast sodium-ion storage.
AB  - Sulfur-functionalized graphene monoliths with a high sulfur fraction (16.8 wt%)
      were prepared to demonstrate a high capacity (~400 mA h g-1 at 0.1 A g-1) and
      ultrafast (~120 mA h g-1 at 5 A g-1) sodium ion storage. The reversible reaction
      of -C-Sx-C- with sodium ions contributes to the extra capacity while a 3D
      graphene network guarantees high rate capability.

PMID- 29637205
TI  - Sulfonate, sulfide and thiolate ligands into an ultrasmall nanocluster:
      [Ag40.13Cu13.87S19(tBuS)20(tBuSO3)12].
AB  - A novel Ag-Cu bimetallic nanocluster, Ag40.13Cu13.87S19(tBuS)20(tBuSO3)12, has
      been synthesized by precise control. The crystal structure reveals that the alloy
      cluster consists of a Cu10Ag2S7 core, a M42(tBuS)20(tBuSO3)12 shell and another
      12 bare S atoms. The sulfonate ligand is observed in NCs for the first time via
      in situ oxidation of thiolate.

PMID- 29637206
TI  - N-Heterocyclic carbene-based ruthenium-hydride catalysts for the synthesis of
      unsymmetrically functionalized double-decker silsesquioxanes.
AB  - Ruthenium-N-heterocyclic carbene complexes with the generic formula
      [RuHCl(CO)(NHC)(PCy3)] exhibit a high catalytic activity toward the (E)-selective
      silylative coupling of divinyl-substituted double-decker silsesquioxanes with two
      distinctly substituted styrenes. This process leads to a novel class of
      unsymmetrically functionalized silsesquioxane derivatives.

PMID- 29637207
TI  - Making good on a promise: ionic liquids with genuinely high degrees of thermal
      stability.
AB  - Thermally robust materials have been of interest since the middle of the past
      century for use as high temperature structural materials, lubricants, heat
      transfer fluids and other uses where thermal stability is necessary or desirable.
      More recently, ionic liquids have been described as 'thermally robust,' with this
      moniker often originating from their low volatility rather than their innate
      stability. As many ionic liquids have vanishingly low vapor pressures, the upper
      limit of their liquid state is commonly considered to be their degradation
      temperature, frequently reported from TGA measurements. The short duration ramps
      often used in TGA experiments can significantly overestimate the temperature at
      which significant degradation begins to occur when the compounds are held
      isothermal for even a few hours. Here, we review our recent work, and that of
      colleagues, in developing thermally robust ionic compounds, primarily
      perarylphosphonium and perarylsulfonium bistriflimide salts, in some of which
      cation stability exceeds that of the anion. We have used a combination of
      molecular design, synthesis, and computational modeling to understand the complex
      tradeoffs involving thermal stability, low melting point and other desirable
      physicochemical properties.

PMID- 29637208
TI  - Tuning the spectral response of ultraviolet organic-inorganic hybrid
      photodetectors via charge trapping and charge collection narrowing.
AB  - Organic-inorganic hybrid ultraviolet photodetectors with tunable spectral
      response are desirable for many different applications. In this work, we blended
      poly[bis(4-phenyl)(2,4,6-trimethylphenyl)amine] (PTAA) with ZnO nanoparticles in
      weight ratios of 1 : 1 and 2 : 1 to create charge traps within the active layers
      for devices with the conventional structure ITO/PEDOT : PSS/PTAA : ZnO/BCP/Al.
      Thin (150-200 nm) and thick (1400-1900 nm) active layers were employed to utilize
      charge collection narrowing (CCN). Both thickness and composition of the active
      layer impacted the spectral tunability of the photoresponse. A single narrow
      response peak centered at 420 nm (the PTAA absorption edge) with a full width at
      half maximum of 12 nm was achieved from the device with a 1900 nm active layer
      and PTAA : ZnO weight ratio of 1 : 1. Decreasing the active layer thickness to
      150 nm resulted in a broad spectral response between 320-420 nm with an external
      quantum efficiency (EQE) value of 295% under 350 nm illumination and a -1 V bias,
      exhibiting photomultiplication via charge trapping and injection even at small
      reverse biases. Increasing the weight ratio of PTAA : ZnO to 2 : 1 lowered both
      the dark current and photocurrent, eliminated photomultiplication in the thin
      device, and diminished the efficacy of CCN to narrow the spectral photoresponse
      in the thick device. Transfer matrix method (TMM) and 3-dimensional finite
      difference time-domain (3D-FDTD) simulations were performed to understand the
      impact of thickness and composition of the active layer on the spectral response
      of UV photodetectors in terms of exciton generation rate and electric field
      distribution within the devices.

PMID- 29637209
TI  - An MTH1-targeted nanosystem for enhanced PDT via improving cellular sensitivity
      to reactive oxygen species.
AB  - Herein, we developed a strategy to attack the cancer cell defense system against
      reactive oxygen species to improve photodynamic therapy efficacy with a
      Ce6@MSN@MTH1 siRNA nanosystem, which was demonstrated to improve cellular
      sensitivity to reactive oxygen species through suppressing MTH1 protein in cancer
      cells.

PMID- 29637210
TI  - Stable metal-organic frameworks as a host platform for catalysis and biomimetics.
AB  - Recent years have witnessed the exploration and synthesis of an increasing number
      of metal-organic frameworks (MOFs). The utilization of stable MOFs as a platform
      for catalysis and biomimetics is discussed. This Feature Article will provide
      insights into the rational design and synthesis of three types of stable MOF
      catalysts on the basis of structural features of MOFs, that is, (i) MOF catalysts
      with catalytic sites on metal nodes, (ii) MOF catalysts with catalytic sites
      immobilized in organic struts, and (iii) MOF catalysts with catalytic centres
      encapsulated in the pores. Then, MOFs used in biomimetics including biomimetic
      mineralization, biosensors and biomimetic replication are introduced. Finally, a
      discussion on the challenges that must be addressed for successful implementation
      of MOFs in catalysis and biomimetics is presented.

PMID- 29637211
TI  - Nonlocal rheology of dense granular flow in annular shear experiments.
AB  - The flow of dense granular materials at low inertial numbers cannot be fully
      characterized by local rheological models; several nonlocal rheologies have
      recently been developed to address these shortcomings. To test the efficacy of
      these models across different packing fractions and shear rates, we perform
      experiments in a quasi-2D annular shear cell with a fixed outer wall and a
      rotating inner wall, using photoelastic particles. The apparatus is designed to
      measure both the stress ratio MU (the ratio of shear to normal stress) and the
      inertial number I through the use of a torque sensor, laser-cut leaf springs, and
      particle-tracking. We obtain MU(I) curves for several different packing fractions
      and rotation rates, and successfully find that a single set of model parameters
      is able to capture the full range of data collected once we account for
      frictional drag with the bottom plate. Our measurements confirm the prediction
      that there is a growing lengthscale at a finite value MUs, associated with a
      frictional yield criterion. Finally, we newly identify the physical mechanism
      behind this transition at MUs by observing that it corresponds to a drop in the
      susceptibility to force chain fluctuations.

PMID- 29637212
TI  - Antibacterial mechanism of silver nanoparticles in Pseudomonas aeruginosa:
      proteomics approach.
AB  - Silver nanoparticles (AgNPs) are the nanomaterials most widely used as
      antimicrobial agents in a range of consumer products, due to the environmental
      release of either the AgNPs themselves or silver ions. Although AgNPs appear to
      be more potent than silver ions, the mechanism behind the activity is not fully
      elucidated yet. The most common mechanism of toxicity of AgNPs proposed to date
      is the release of silver ions and/or the particle-specific functions. In this
      study, Pseudomonas aeruginosa (a model for Gram-negative bacteria) was treated
      with AgNPs, and its proteomic response was comprehensively characterized to
      elucidate the antimicrobial mechanism of AgNPs in the microorganism. In total, 59
      silver-regulated proteins (27 up-regulated and 32 down-regulated proteins) and 5
      silver-binding proteins were identified. Bioinformatic analysis revealed that
      interference with the cell-membrane function and generation of intracellular
      reactive oxygen species (ROS) were the main pathways for the antibacterial
      effect. The pattern of membrane proteins regulated by AgNPs was similar to that
      found for silver ions. In addition, the same silver-binding proteins were
      obtained with both AgNPs and silver ions, which indicated that AgNPs probably
      affect the cell membrane and react with proteins by releasing silver ions. The
      elevation of intracellular ROS relative to that with silver ions confirmed
      oxidative damage caused by AgNPs, which may be ascribed to the nano
      characteristics and higher uptake efficiency of the particles. These results
      demonstrate that the antimicrobial activity of AgNPs is due to the synergistic
      action of release of dissolved silver ions and particle-specific effects. The
      proteomic analysis of silver-binding and silver-regulated proteins in the present
      study provides insight into the mechanism of antimicrobial activity of such
      nanomaterials.

PMID- 29637213
TI  - Translating MOF chemistry into supramolecular chemistry: soluble coordination
      nanofibers showing efficient photon upconversion.
AB  - A method for synthesizing coordination nanofibers by extracting the structural
      motifs of metal-organic frameworks (MOFs) is demonstrated. In these soluble
      nanofibers, multiple chromophores with largely different sizes and shapes can be
      arranged at desired compositions, and excited triplet energy migrates among the
      densely assembled chromophore arrays, showing an efficient photon upconversion
      even at very low concentration.

PMID- 29637214
TI  - Influence of geometric design characteristics on primary stability of orthodontic
      miniscrews.
AB  - OBJECTIVE: Aim of the present study was to investigate the influence of geometric
      design characteristics on primary stability of orthodontic miniscrews. MATERIALS
      AND METHODS: Forty self-drilling miniscrews with different geometric design
      characteristics were divided into the following groups (n = 10): group I-Tomas(r)
      (Dentaurum, Germany), group II-AbsoAnchor(r) (Dentos, Korea), group III-HUBIT(r)
      miniscrew (HUBIT, Korea), group IV-Creative(r) (China). The four types were
      conical miniscrews with 1.6 mm diameter and 6.0 mm length. The miniscrews were
      manually inserted perpendicular to cow ribs until the full thread length was
      reached with the help of a 1.3 mm predrilled pilot hole. Each miniscrew was
      evaluated using scanning electron microscope. Linear and angular measurements
      were taken using Photoshop CS3 software. Miniscrew stability was measured by the
      Periotest(r) and pullout test. RESULTS: All linear and angular measurements of
      the geometric characteristics showed significant differences between the four
      groups (p <= 0.001). Results of the pullout test showed significant differences
      between the four groups (p <= 0.001), while the Periotest(r) values showed no
      significant differences (p = 0.122). A multiple linear regression analysis
      revealed the significant predictors for higher pullout: a larger flank, a higher
      value for the thread angle, lead angle, and apical face angle (p <= 0.001).
      CONCLUSIONS: Orthodontic miniscrews' geometric design characteristics
      significantly affected the primary stability. Larger pitch width, flank, thread
      angle, apical face angle, and/or lead angle led to higher primary stability.
      Smaller a thread shape factor (TSF) also improved primary stability. Varying
      these characteristics may enhance miniscrew design.

PMID- 29637215
TI  - [Cost-effectiveness analysis of blue light cystoscopy with hexylaminolevulinate
      in transurethral resection of the bladder].
AB  - BACKGROUND: Photodynamic diagnosis using the optical imaging agent
      hexaminolevulinate (HAL, Hexvix(r), Ipsen Pharma GmbH, Ettlingen, Germany) as an
      adjunct to white light cystoscopy (WLC) during the initial transurethral
      resection of bladder tumours (TURB) improves the detection rate of bladder cancer
      and leads to fewer recurrences. OBJECTIVES: A cost-effectiveness analysis was
      carried out in order to calculate the consequences for the German healthcare
      system. METHODS: We combined a short-term decision tree and a Markov model to
      evaluate outcomes over a long period of time. The alternatives investigated were
      HAL-assisted blue light cystoscopy (BLC) as adjunct to WLC (HAL + BLC/WLC)
      compared with WLC alone in patients undergoing TURB. RESULTS: HAL + BLC/WLC
      compared to WLC alone was associated with 0.07 incremental quality-adjusted life
      years (QALYs) and cost savings of 537 ? per patient. CONCLUSION: HAL + BLC/WLC
      compared with WLC alone resulted in both cost savings and improved patient
      outcome rendering it the "dominant" strategy.

PMID- 29637216
TI  - [Advanced bladder cancer : From chemo- to immunotherapy].
AB  - In November 2016, the results of a phase III clinical trial with the protein cell
      death (PD)-1 inhibitor pembrolizumab for second-line treatment of metastatic
      urothelial carcinoma were published and showed an overall survival benefit in
      comparison with conventional chemotherapy with vinflunine, docetaxel, or
      paclitaxel. In a similar trial the PD-L1 antibody atezolizumab showed no
      significant benefit in comparison to chemotherapy in the subgroup of PD-L1
      positive patients and, thus, missed its primary endpoint. For other PD-1/PD-L1
      directed substances, large phase I/II trials reported data concerning response
      rates and overall survival. This substance class will most likely become the new
      treatment standard in second-line treatment of metastatic urothelial cancer.
      Currently, PD-1/PD-L1 inhibitors are also being tested within randomized phase
      III trials for first-line treatment using different approaches either as a
      monotherapy or a combination with conventional chemotherapy or cytotoxic T
      lymphocyte-associated protein (CTLA)-4 inhibitors. Whereas data from single-arm
      phase II clinical trials have already been published, preliminary phase III data
      are expected in 2018.

PMID- 29637217
TI  - ["Stay and play" in football : Art of keeping players fit to play].
AB  - Many publications about the treatment and return to play after severe football
      injuries are available from the scientific literature, particularly about
      injuries requiring surgery. In contrast, less severe football injuries, such as
      muscle strains, ankle sprains and contusions, are less well addressed in the
      literature although these represent the most frequent type of injury.
      Additionally, such reports often have a low level of evidence and guidelines on
      treatment and the return to play process are very rare. Thus, the time away from
      football and the timing of return to play after minor injuries depends on the
      experience and skills of the responsible medical team. To achieve the aim of stay
      and play on the field, the medical team should be highly knowledgeable in
      interdisciplinary football medicine, prevention strategies, first aid on the
      field, clinical and manual diagnostics, tissue regeneration, symptomatic and
      conservative treatment as well as in return to play decision-making. No consensus
      exists on stay and play procedures neither on the practical level nor on the
      scientific level regarding injury definition, the diagnostic and treatment
      options and stay and play criteria. Therefore, this article presents the first
      steps for assessing stay and play strategies after minor injuries to standardize
      and improve practical routine, education and scientific research.

PMID- 29637218
TI  - [The care of relatives and ICU teams during a crisis].
AB  - Families find themselves in an exceptional situation after the sudden death of
      someone close. Anxiety, aggression, rage, incomprehension, and distraction are
      only a few feelings of the concerned people which intensive care staff must take
      care of. Crisis intervention, developed in the middle of the last century, offers
      a framework with its concepts for the healthcare staff of how to work with the
      bereaved people during the first few hours. The BASIS model is a sort of
      counseling technique that guides nurses and physicians: bonding and urging the
      acceptance of the facts, providing structure and information, and securing backup
      support networks. Professionals who offer help need a high level of empathy and
      compassion for their work. But it is essential to offer help only in situations
      where advice is possible. Otherwise, physicians and nurses are at high risk to
      develop compassion fatigue. The right training, advanced education, and
      supervision are necessary, so that healthcare professionals can support people in
      crisis.

PMID- 29637219
TI  - [Community-acquired pneumonia].
AB  - Community-acquired pneumonia (CAP) is a frequent and potentially fatal disorder.
      Due to the notably high mortality within the first days, the immediate initiation
      of rational diagnostic pathways and treatment is of tremendous prognostic impact.
      In this review article, the current German guideline on the diagnosis and therapy
      of CAP is presented. Special focus is put on structured patient management based
      on the individual risk for early identification of critically ill patients. In
      particular, risk assessment directly influences rational diagnostics and adequate
      therapy. New recommendations concerning preventive strategies are also discussed
      in this article.

PMID- 29637220
TI  - Gout as a risk factor for osteoporosis: response to comments by Kostev.

PMID- 29637221
TI  - Association between gout and osteoporosis risk in the United Kingdom.

PMID- 29637222
TI  - Innovation in Cell Banking, Expansion, and Production Culture.
AB  - Cell culture-based production processes enable the development and commercial
      supply of recombinant protein products. Such processes consist of the following
      elements: thaw and initiation of culture, seed expansion, and production culture.
      A robust cell source storage system in the form of a cell bank is developed and
      cells are thawed to initiate the cell culture process. Seed culture expansion
      generates sufficient cell mass to initiate the production culture. The production
      culture provides an environment where the cells can synthesize the product and is
      optimized to deliver the highest possible product concentration with acceptable
      product quality. This chapter describes the significant innovations made in these
      process elements and the resulting improvements in the overall efficiency,
      robustness, and safety of the processes and products.

PMID- 29637223
TI  - Next Generation Biopharmaceuticals: Product Development.
AB  - Therapeutic proteins show a rapid market growth. The relatively young biotech
      industry already represents 20 % of the total global pharma market. The biotech
      industry environment has traditionally been fast-pasted and intellectually
      stimulated. Nowadays the top ten best selling drugs are dominated by monoclonal
      antibodies (mABs).Despite mABs being the biggest medical breakthrough in the last
      25 years, technical innovation does not stand still.The goal remains to preserve
      the benefits of a conventional mAB (serum half-life and specificity) whilst
      further improving efficacy and safety and to open new and better avenues for
      treating patients, e.g., improving the potency of molecules, target binding,
      tissue penetration, tailored pharmacokinetics, and reduced adverse effects or
      immunogenicity.The next generation of biopharmaceuticals can pose specific
      chemistry, manufacturing, and control (CMC) challenges. In contrast to
      conventional proteins, next-generation biopharmaceuticals often require
      lyophilization of the final drug product to ensure storage stability over shelf
      life time. In addition, next-generation biopharmaceuticals require analytical
      methods that cover different ways of possible degradation patterns and pathways,
      and product development is a long way from being straight forward. The element of
      "prior knowledge" does not exist equally for most novel formats compared to
      antibodies, and thus the assessment of critical quality attributes (CQAs) and the
      definition of CQA assessment criteria and specifications is difficult, especially
      in early-stage development.

PMID- 29637224
TI  - [Rhinophyma : Successful treatment with low-dose oral isotretinoin].
AB  - Rhinophyma is a form of rosacea and is often cosmetically disfiguring. There are
      various therapeutic ablation modalities. Surgery is often associated with down
      time and side-effects. We describe successful treatment with low-dose
      isotretinoin as a safe alternative with a lower risk of complications. We also
      discuss the advantages and disadvantages of various therapeutic modalities.

PMID- 29637225
TI  - [Phlebological emergencies].
AB  - BACKGROUND: Deep and superficial vein thromboses as well as variceal hemorrhages
      are emergencies. The risk of short- and long-term morbidity and mortality in vein
      thromboses is increased. Variceal hemorrhage harbors the risk of massive blood
      loss. Prompt and adequate therapy of these diseases is therefore essential.
      OBJECTIVES: Our aim was to give an overview of these phlebological emergencies.
      MATERIALS AND METHODS: Based on the current guidelines and supplemented by a
      selective literature search in PubMed, we summarize the most important aspects
      for clinical practice. RESULTS: In deep vein thrombosis, therapeutic
      anticoagulation and compression therapy are indicated for a duration of at least
      3-6 months. A shorter duration is associated with a considerably increased
      recurrence rate. Basic measures in superficial vein thrombosis comprise
      mobilization, cooling, and compression. In case of tenderness on palpation, non
      steroidal anti-inflammatory drugs are recommended. Indication for anticoagulation
      and its dose depends on length of the thrombus and distance of the proximal part
      of the thrombus towards the deep veins. Variceal hemorrhage is a complication of
      advanced varicosis and can usually be handled with simple measures such as
      elevation of the extremity and compression. CONCLUSIONS: Prompt diagnosis and
      therapy is essential in superficial and deep vein thrombosis to prevent short
      term complications such as pulmonary embolism and growth of the thrombus as well
      as long-term complications such as postthrombotic syndrome with secondary
      varicosis and chronic leg ulcer. After the occurrence of varicophlebitis or
      variceal hemorrhage, treatment of varicosis is indicated to prevent recurrences.

PMID- 29637227
TI  - [Complex challenges require comprehensive solutions].

PMID- 29637226
TI  - Altered Profiles of Gut Microbiota in Klebsiella pneumoniae-Induced Pyogenic
      Liver Abscess.
AB  - Intestinal microbiota plays a crucial role in preventing the colonization and
      invasion by pathogens, and disruption of microbiota may cause opportunistic
      infections and diseases. Pathogens often have strategies to escape from the
      colonization resistance mediated by microbiota, but whether they also modulate
      the microbiota composition is still a topic of investigation. In the present
      study, we addressed this question using an opportunistic pathogen, Klebsiella
      pneumoniae serotype K1, which is known to cause pyogenic liver abscess (KLA) in
      about 30% of mice. We examined the effect of K. pneumoniae infection on cecal
      microbiota composition by performing high-throughput 454 pyrosequencing of the
      hypervariable V3-V4 regions of bacterial 16S rRNA gene. Our data revealed that K.
      pneumoniae inoculation substantially changed the cecal microbiota composition
      when analyzed at the phylum, order, and family levels. Most strikingly, the KLA
      infected mice had significantly increased abundance of Bacteroidales and
      Enterobacteriales and decreased abundance of Lactobacillales and Eggerthellales.
      Furthermore, by comparing the infected mice with or without KLA disease symptoms,
      we identified specific microbiota changes associated with the KLA disease
      induction. Especially, the KLA group had dramatically decreased sequence
      identical to Lactobacillus compared with non-KLA mice. These findings suggest
      that the pathogenic process of KLA infection may involve alteration of microbiota
      compositions, particularly reduction in Lactobacillus.

PMID- 29637229
TI  - Effect of levosimendan in patients with acute decompensated heart failure : A
      meta-analysis.
AB  - BACKGROUND: Acute decompensated heart failure (ADHF) is associated with high
      morbidity and mortality. Intravenous inotropic agents play an important role in
      treating ADHF. Relatively small clinical studies have evaluated the effects of
      levosimendan, a positive inotropic agent with calcium-sensitizing effects, in
      ADHF. The present meta-analysis pooled these studies to assess the clinical
      efficacy of levosimendan in ADHF. MATERIALS AND METHODS: The PubMed, MEDLINE,
      Cochrane Library, and ClinicalTrials.com databases were systematically searched
      for prospective clinical studies published in English up to May 2017 on effects
      of levosimendan alone or versus other agents (placebo [glucose], dopamine,
      furosemide) on left ventricular ejection fraction (LVEF), brain natriuretic
      peptide (BNP) level, and heart rate (HR) in patients with ADHF. RESULTS: Seven
      articles were selected with 132 patients for levosimendan and 125 patients for
      control groups. Compared with controls (except dopamine) or after vs. before use,
      levosimendan was associated with a significantly reduced BNP level (standardized
      mean difference [SMD]: -0.70; 95% confidence interval [CI]: -0.92, -0.48; p =
      0.000; I2 = 22.0%), as well as improved LVEF (SMD: 0.47; 95%CI: 0.12, 0.81; p =
      0.008; I2 = 63.3%) and increased HR (SMD: 0.39; 95% CI: 0.15, 0.63; p = 0.002; I2
      = 23.6%) when comparing after vs. before use but not in comparisons to controls.
      CONCLUSION: In the present meta-analysis, levosimendan infusion in patients with
      ADHF appeared to reduce BNP regardless of the comparator (except for dopamine),
      and also improve LVEF and increase HR in after vs. before use comparisons but not
      compared to controls. Future larger studies on the benefit of levosimendan in
      ADHF patients are warranted.

PMID- 29637230
TI  - Contrast agent dose and slow/no-reflow in percutaneous coronary interventions : A
      case-control study of patients with non-ST-segment elevation acute coronary
      syndromes.
AB  - BACKGROUND: The angiographic slow/no-reflow phenomenon after primary percutaneous
      coronary intervention carries a poor prognosis for patients with non-ST-segment
      elevation acute coronary syndrome (NSTEACS). There is evidence that contrast
      agents cause endothelial dysfunction, myocardial cell damage, and coronary
      spasms. We hypothesized that the contrast agent dose may be related to slow/no
      reflow in patients with NSTEACS undergoing percutaneous transluminal coronary
      angioplasty and stent (PTCA + stent). PATIENTS AND METHODS: We enrolled 3369
      patients with NSTEACS who underwent PTCA + stent only in the culprit vessel for
      the first time from September 2007 to May 2017 in this study. Coronary blood flow
      of <=TIMI grade 2 after PTCA + stent was defined as slow/no-reflow. The
      relationship between the contrast agent dose and slow/no-reflow phenomenon was
      analyzed by multivariate conditional logistic regression and smooth curve
      fitting. RESULTS: In multivariable conditional logistic regression analysis, the
      contrast agent dose was found to be an independent risk factor for slow/no-reflow
      after adjusting for the number of stents and the thrombus burden (OR: 1.0112; 95%
      CI: 1.0049-1.0176; p < 0.0001), and after adjusting for type 2 diabetes mellitus,
      NSTEACS risk stratification, application of platelet glycoprotein (GP) IIB/IIIA
      receptor antagonists, type of contrast agent, number of balloon dilatations,
      number of stents, and thrombus burden (OR: 1.0113; 95% CI: 1.0036-1.0191; p =
      0.004). Further, the risk of slow/no-reflow increased significantly with the
      contrast agent level up to the inflection point of 160 ml. CONCLUSION: The
      contrast agent dose may be a risk factor for slow/no-reflow phenomenon after PTCA
      + stent in patients with NSTEACS. When the dose was greater than 160 ml, the risk
      of slow/no-reflow increased significantly.

PMID- 29637231
TI  - Minimally invasive direct coronary bypass surgery via distal mini-sternotomy :
      Promising clinical results with anaortic, multivessel, all-arterial technique.
AB  - BACKGROUND: Minimally invasive direct coronary artery bypass grafting (MIDCAB)
      was developed to decrease perioperative morbidity, some of which may be related
      to the use of cardiopulmonary bypass and to cross-clamping of the aorta. We
      report our initial experience with multivessel MIDCAB via distal mini-sternotomy
      (DIMS). DIMS is performed to gain access to the left and right internal thoracic
      arteries and to reach the left anterior descending coronary artery (LAD),
      diagonal branches, and right coronary artery (RCA). METHODS: Between January 2016
      and January 2017, 12 patients with significant coronary artery disease of the LAD
      and the RCA underwent multivessel, all-arterial MIDCAB through a distal midline
      skin incision from the fourth intercostal space to the xyphoid process, with L-
      or T-shaped division of the sternum. The mean age of the patients was 61.5 +/-
      5.2 years (range: 52-71 years). RESULTS: We performed all-arterial
      revascularization using the left internal mammary artery in 12 patients, the
      radial artery in ten, and the right internal mammary artery in two patients. The
      mean number of grafts per patient was 2.08 +/- 0.4 (range: 2-3). The mean length
      of the skin incision was 8.5 +/- 1.3 cm (range: 7-11 cm). There was no
      perioperative ischemia, postoperative bleeding, or arrhythmia events. No
      postoperative cognitive dysfunction occurred. The mean hospital stay was 5.6
      days. No major adverse cardiac events (MACE) occurred at the 12-month follow-up.
      At follow-up, all patients were in New York Heart Association class I and there
      were no wound complications. CONCLUSION: Although MIDCAB-DIMS is technically more
      demanding than conventional procedures and our experience is limited, we conclude
      that this technique can be used safely in selected patients, with promising 12
      month follow-up results.

PMID- 29637228
TI  - Engineering CRISPR/Cpf1 with tRNA promotes genome editing capability in mammalian
      systems.
AB  - CRISPR/Cpf1 features a number of properties that are distinct from CRISPR/Cas9
      and provides an excellent alternative to Cas9 for genome editing. To date, genome
      engineering by CRISPR/Cpf1 has been reported only in human cells and mouse
      embryos of mammalian systems and its efficiency is ultimately lower than that of
      Cas9 proteins from Streptococcus pyogenes. The application of CRISPR/Cpf1 for
      targeted mutagenesis in other animal models has not been successfully verified.
      In this study, we designed and optimized a guide RNA (gRNA) transcription system
      by inserting a transfer RNA precursor (pre-tRNA) sequence downstream of the gRNA
      for Cpf1, protecting gRNA from immediate digestion by 3'-to-5' exonucleases.
      Using this new gRNAtRNA system, genome editing, including indels, large fragment
      deletion and precise point mutation, was induced in mammalian systems, showing
      significantly higher efficiency than the original Cpf1-gRNA system. With this
      system, gene-modified rabbits and pigs were generated by embryo injection or
      somatic cell nuclear transfer (SCNT) with an efficiency comparable to that of the
      Cas9 gRNA system. These results demonstrated that this refined gRNAtRNA system
      can boost the targeting capability of CRISPR/Cpf1 toolkits.

PMID- 29637232
TI  - [Low-threshold consulting services for dementia : Quality criteria from a
      provider's point of view].
AB  - BACKGROUND: Low-threshold consulting services are becoming increasingly more
      important as an addition to outpatient and inpatient services. OBJECTIVE: What
      quality criteria do providers of low-threshold consulting services for family
      caregivers of people with dementia have? MATERIAL AND METHODS: Telephone
      interviews with 36 providers of family counseling, support groups, care course.
      Qualitative content analysis according to Mayring complemented by a literature
      search. RESULTS: The quality criteria of the providers are based on frequent,
      ongoing, daily life-oriented, family-oriented, relief-providing, professional,
      and cross-linked services. CONCLUSION: Increased cooperation and coordination of
      all involved stakeholders is necessary to improve the knowledge and utilization
      of the services and the qualitative orientation.

PMID- 29637233
TI  - [Quality of life among older informal caregivers of people with dementia].
AB  - BACKGROUND: In Germany, informal caregiving becomes an increasingly important
      issue especially for people with dementia. Spouses often provide nursing care due
      to the limited daily living skills of people with dementia. This leads to a wide
      range of caregiver burden and decreased quality of life (QoL). Analyses on the
      relation between QoL and caregiver burden of older informal caregivers in Germany
      are rare. OBJECTIVE: The following research questions were assessed: (1) Does
      caregivers' QoL differ from that of the older general population?; (2) Which
      sociodemographic, health- and care-related characteristics affect caregivers'
      QoL? MATERIAL AND METHODS: For this study, two samples (aged 60 years and older)
      were recruited: informal caregivers (n = 119) and a representative sample of
      older non-caregivers in the general population (n = 1133). Linear regression
      analyses were applied to examine the effects of sociodemographic, health and care
      related variables on the QoL of older informal caregivers of people with
      dementia. RESULTS: Older informal caregivers reported a significantly lower QoL
      compared to older non-caregivers in the general population. Especially the
      domains autonomy, activities in the past, the present and the future as well as
      intimacy were negatively associated with caregivers' QoL. CONCLUSION: The results
      of the study highlighted caregivers' need for assistance. Due to demographic
      changes, tailored support services should be based on older caregivers' needs.

PMID- 29637235
TI  - Correction to: Unconstrained total knee arthroplasty in significant valgus
      deformity: a modified surgical technique to balance the knee and avoid
      instability.
AB  - The author would like to correct the following errors in the publication of the
      original article.

PMID- 29637234
TI  - [Informal care for dementia according to type of service].
AB  - BACKGROUND: Dementia is a major challenge for society and its impact will grow in
      the future. Informal care is an essential part of dementia care. Previous studies
      considered informal care as a whole and not by its components. OBJECTIVE: We
      aimed to assess the degree of association between specific informal care services
      and dementia. MATERIAL AND METHODS: This analysis is based on data from the
      seventh wave of the AgeCoDe/AgeQualiDe study. Dementia was diagnosed based on the
      DSM-IV criteria. Severity of dementia was assessed and categorized by means of
      the Clinical Dementia Rating and eight individual informal care services were
      considered. Logistic regression models were used to assess associations. RESULTS:
      Of the 864 participants 18% suffered from dementia (very mild: 4%; mild: 6%;
      moderate: 5%; severe: 3%). All informal care services were significantly
      associated with dementia, with an emphasis on "supervision", "regulation of
      financial matters" and "assistance in the intake of medication". Considering
      different degrees of dementia severity, similar results arose from the analyses.
      All three aforementioned services showed a pronounced association with all
      degrees of dementia severity, except for supervision and very mild dementia.
      CONCLUSION: The provision of all types of informal care services is associated
      with dementia. The association is pronounced for services that can be more easily
      integrated into the daily routines of the informal caregiver. Policy makers who
      plan to integrate informal care into the general care arrangements for dementia
      should consider this.

PMID- 29637236
TI  - Distinct extra-articular invasion patterns of diffuse pigmented villonodular
      synovitis/tenosynovial giant cell tumor in the knee joints.
AB  - PURPOSE: Pigmented villonodular synovitis (PVNS)/tenosynovial giant cell tumor
      (TGCT) is a benign, proliferative lesion of the synovium, the bursa, and the
      tendon sheath. Little is known about the anatomical distribution pattern of
      diffuse extra-articular PVNS/TGCT around the knee joint. In this retrospective
      study, anatomical distribution of PVNS/TGCT using magnetic resonance imaging
      (MRI) and arthroscopy was analyzed. METHODS: This study was designed as a
      retrospective, observational cross-sectional study based on MRI and arthroscopy.
      Twenty-four PVNS/TGCT patients (24 knees) who underwent arthroscopic or posterior
      open surgery between 2009 and 2016 were enrolled. Of these, eight intra-articular
      and 16 diffuse extra-articular PVNS/TGCT of the knee were classified. The
      anatomical locations of the PVNS/TGCT masses were determined with a newly devised
      mapping scheme. Analysis was performed on the prevalence of each compartment and
      agreement rates between each compartment. RESULTS: The point prevalence of intra
      articular posterior compartment was higher in diffuse extra-articular PVNS/TGCT
      group compared with intra-articular PVNS/TGCT group. The point prevalence of
      diffuse PVNS/TGCT was most prevalent in the extra-articular posterolateral
      compartment (12 out of 16 diffuse extra-articular PVNS/TGCT patients, 75%) and
      second most common in the below to joint capsule compartment (11 out of 16,
      68.8%). The agreement rate was the highest between intra-articular posterolateral
      and extra-articular posterolateral compartments (75%). CONCLUSION: Extra
      articular invasion of diffuse PVNS/TGCT occurred in specific patterns in the knee
      joint. Extra-articular lesions were always accompanied by lesions in intra
      articular compartments. In particular, lesions in the intra-articular posterior
      compartments were observed in all of the diffuse extra-articular PVNS/TGCT
      patients. The point prevalence of diffuse extra-articular PVNS/TGCT for each
      compartment was the highest [12 out of 16 (75%)] in extra-articular
      posterolateral compartment. In contrast, invasion to the extra-articular
      posteromedial side was less frequent [5 out of 16 (31.3%)] than to the extra
      articular posterolateral side. Knowing where the lesions frequently occur may
      provide important information for deciding the timing, method, and extent of
      surgery. LEVEL OF EVIDENCE: Level IV.

PMID- 29637237
TI  - [Three cases of severe chronic diarrhea with a rare cause and a simple therapy].
AB  - We report three cases of severe olmesartan-associated chronic diarrhea with
      weight loss and malassimilation syndrome. Histologically, a sprue-like
      enteropathy was diagnosed in each case, while serological tests for celiac
      disease were negative. After stopping the medication, symptoms improved within a
      few days. Histologically, remission was documented after 3 months. Olmesartan
      associated enteropathy is an underestimated entity and an important differential
      diagnosis in patients with chronic diarrhea.

PMID- 29637238
TI  - [Comorbidities of heart failure: sleep apnea].
AB  - BACKGROUND: Since sleep apnea often occurs in heart failure, physicians regularly
      need to decide whether further diagnostic procedures and/or treatment are
      required. OBJECTIVES: Which types of sleep apnea occur in heart failure patients?
      When is treatment needed? Which treatments and treatment goals are appropriate?
      MATERIALS AND METHODS: Clinical trials and guidelines as well as their
      implementation in clinical practice are discussed. RESULTS: At least 40% of
      patients with heart failure, both with reduced and preserved left ventricular
      ejection fraction (HFrEF and HFpEF, respectively), suffer from relevant sleep
      apnea. In heart failure patients both obstructive and central sleep apnea are
      associated with increased mortality. In HFrEF as well as in HFpEF patients with
      obstructive sleep apnea, treatment with continuous positive airway pressure
      (CPAP) achieves symptomatic and functional improvements. In patients with HFpEF,
      positive airway pressure treatment of central sleep apnea may be beneficial. In
      patients with HFrEF and left ventricular ejection fraction <=45%, adaptive
      servoventilation is contraindicated. CONCLUSIONS: Sleep apnea is highly prevalent
      in heart failure patients and its treatment in specific patient groups can
      improve symptoms and functional outcomes. Thus, testing for sleep apnea is
      recommended.

PMID- 29637239
TI  - [Cachexia and sarcopenia in chronic heart failure : Change in muscle strength and
      muscle structure].
AB  - Alterations to the body composition, i.e. the makeup of skeletal muscle, fat and
      bone density, are frequent in heart insufficiency. Their prevalence and clinical
      consequences are often underestimated. Cachexia is recognized as a complex
      multifactorial syndrome in chronic diseases that leads to weight loss. This point
      constitutes the essential differential criterion from sarcopenia. Cachexia is
      defined as a non-edematous weight loss of more than 5% within 12 months or less.
      Cachexia means weight loss, while sarcopenia means loss of muscle mass without
      weight loss because the functional muscle can be replaced by adipocytes.
      Sarcopenia is defined as a skeletal muscle mass index (SMMI) of at least 2
      standard deviations below the mean value of a healthy young reference group
      between 20 and 30 years of the same sex and ethnic background. At the same time
      the walking speed is reduced to 1 m/s or the distance covered in a 6-min walk is
      <400m. The determination of loss of muscle mass should be carried out by whole
      body scanning, ideally with dual-energy x-ray absorptiometry. A reliable and
      simple method for measurement of performance capability is the short physical
      performance battery (SPPB) test. The treatment of sarcopenia and cardiac cachexia
      in patients with heart insufficiency is still a great challenge. Power and
      endurance training, nutritional supplementation and drug therapy are possible
      therapeutic approaches; however, the study situation is unsatisfactory.

PMID- 29637241
TI  - [Abscess of unusual origin in the upper abdomen of a youth].

PMID- 29637240
TI  - [Symptomatic hypocalcemia after thyroidectomy : Prevention by a combination of
      prophylaxis and risk-adapted substitution].
AB  - BACKGROUND: Treatment of hypocalcemia after thyroidectomy consists of an
      individual substitution, prophylaxis or a daily administration of calcium/vitamin
      D3. OBJECTIVE: Does prophylactic therapy combined with a risk-adapted
      substitution of calcium and vitamin D3 reduce symptomatic hypocalcemia compared
      to individual substitution? MATERIAL AND METHODS: After implementation of a new
      algorithm, patient data were prospectively documented and analyzed compared to a
      historical patient population. The algorithm consisted of a single prophylactic
      i. v. administration of calcium (1 g calcium gluconate 10% in 250 ml saline) and
      a risk-adapted oral administration of calcium and vitamin D3 after surgery.
      Patients without risk (parathyroid hormone, PTH > 15 pg/ml) were not treated.
      Patients with a low risk (PTH >= 6 <= 15 pg/ml and Ca > 2.0 mmol/l) received 3 g
      calcium, patients with a high risk (PTH >= 6 <= 15 pg/ml and Ca < 2.0 mmol/l)
      received 3 g calcium and 2 * 0.5 ug vitamin D3 and patients with a very high risk
      (PTH < 6 pg/ml) got 4 g calcium and 2 * 0.5 ug vitamin D3. RESULTS: In this study
      415 patients were included (230 prospectively and 185 retrospectively). Serum
      calcium of patients with individual substitution increased significantly at day 1
      (p = 0.0001) and the number of patients with critical hypocalcemia (Ca < 2.0
      mmol/l) decreased by half (27% vs. 12.2%; p = 0.0001). There was a significantly
      lower rate of symptomatic patients (24.9% vs 13.0%; p = 0.002) and a clear
      reduction of patients with a prolonged hospitalization (10.8% vs. 6.5%; p =
      0.08). The rate of permanent hypocalcemia was comparable (2.2% vs. 2.1%). In the
      risk groups there was a significantly different rate of hypocalcemia: patients
      without risk (n = 170) in 2.2%, patients with low risk (n = 36) in 25%, patients
      with high risk (n = 13) in 69.2% and patients with very high risk (n = 11) in
      71%. CONCLUSION: This new treatment regimen is practicable, significantly lowers
      the symptoms, also in comparison to the literature and shows a clear
      differentiation between the risk groups.

PMID- 29637242
TI  - [Transoral thyroid and parathyroid surgery : Implementation and evaluation of the
      transoral endoscopic technique via the vestibular approach (TOETVA)].
AB  - BACKGROUND: More than 10 years ago various research groups in Germany first
      reported the possibility of transoral surgery of the thyroid and parathyroid
      glands. These were developed and evaluated within the framework of natural
      orifice transluminal endoscopic surgery (NOTES). While development of these
      innovative and new techniques that enabled surgery without visible scars did not
      become well accepted in Europe and America, it led to an optimized transoral
      endoscopic thyroidectomy vestibular approach (TOETVA), which was implemented
      particularly in Asia. We report the preparation, step-by-step implementation, and
      first promising results for TOETVA of an international surgical cooperation.
      MATERIAL AND METHODS: A Thai-Austrian-German cooperation was started in June
      2017. Between June and November 2017 the first 10 TOETVA procedures were
      performed in female and male patient(s) presenting with single thyroid nodules,
      sporadic primary hyperparathyroidism and solitary parathyroid adenoma or
      thyroglossal duct cysts. The TOETVA technique was performed using 3 laparoscopic
      ports inserted at the oral vestibule and a CO2 insufflation pressure at 6-8 mm
      Hg. Each surgery was performed using laparoscopic instruments and ultrasonic or
      bipolar devices. Surgical outcome, complications and conversions to an open
      technique were recorded. RESULTS: Of the patients six presented with single
      thyroid nodules, two patients had multinodular goitre with scintigraphically cold
      nodules and multifocal hyperfunctioning thyroid tissue, one patient suffered from
      sporadic primary hyperparathyroidism with a left sided parathyroid adenoma and
      one patient suffered from a thyroglossal duct cyst. No conversion to conventional
      open surgery was necessary. Average tumor size was 3.1 cm (range 1-4 cm). There
      was no relevant loss of blood or subsequent bleeding. No temporary or permanent
      hoarseness or mental nerve injury occurred, while transient hypoparathyroidism
      was evident after successful parathyroid resection. Of the patients five
      developed a slight postoperative hematoma in the submandibular region. No
      infections or disorders of wound healing occurred. CONCLUSION: The TOETVA
      technique is feasible and safe in selected patients; however, further prospective
      studies are necessary to evaluate the value of the procedure, risks and long-term
      results.

PMID- 29637243
TI  - [Surgical strategies for small sporadic neuroendocrine pancreatic tumors].
AB  - Small (<2 cm) sporadic neuroendocrine pancreatic neoplasms (pNENs) are a
      heterogeneous group of neoplasms, which can be separated into functionally active
      or non-functional tumors. Functionally active pNENs release various hormones,
      such as insulin, gastrin, glucagon and vasoactive intestinal hormones and
      therefore lead to severe symptoms independent of their size. The main symptoms
      include hypoglycemia, coma (insulinoma), diarrhea (gastrinoma, VIPoma),
      intestinal ulcers (gastrinoma) and hyperglycemia (glucagonoma). Asymptomatic
      inactive pNENs do not cause a hormonal syndrome even though in
      immunohistochemistry they are positive for various hormones and endocrine markers
      (e.g. chromogranin and synaptophysin). Non-active small pNENs are increasingly
      being found because of the widespread use of high-resolution imaging and are
      named incidental pNENs. The current therapy algorithms of small functionally
      active and non-functional pNENs are very different and include besides non
      operative management and surveillance (wait and see strategy) of non-active pNENs
      (G1, low G2), all minimally invasive, open and robotic techniques of pancreas
      resection. Until today almost all recommendations of surgical and nonsurgical
      therapy algorithms have been established based on retrospective data.

PMID- 29637245
TI  - ?

PMID- 29637246
TI  - ?

PMID- 29637244
TI  - [Hyperspectral imaging of gastrointestinal anastomoses].
AB  - INTRODUCTION: Anastomotic insufficiency (AI) remains the most feared surgical
      complication in gastrointestinal surgery, which is closely associated with a
      prolonged inpatient hospital stay and significant postoperative mortality.
      Hyperspectral imaging (HSI) is a relatively new medical imaging procedure which
      has proven to be promising in tissue identification as well as in the analysis of
      tissue oxygenation and water content. Until now, no data exist on the in vivo HSI
      analysis of gastrointestinal anastomoses. METHODS: Intraoperative images were
      obtained using the TIVITATM tissue system HSI camera from Diaspective Vision GmbH
      (Pepelow, Germany). In 47 patients who underwent gastrointestinal surgery with
      esophageal, gastric, pancreatic, small bowel or colorectal anastomoses, 97
      assessable recordings were generated. Parameters obtained at the sites of the
      anastomoses included tissue oxygenation (StO2), the tissue hemoglobin index
      (THI), near-infrared (NIR) perfusion index, and tissue water index (TWI).
      RESULTS: Obtaining and analyzing the intraoperative images with this non-invasive
      imaging system proved practicable and delivered good results on a consistent
      basis. A NIR gradient along and across the anastomosis was observed and,
      furthermore, analysis of the tissue water and oxygenation content showed specific
      changes at the site of anastomosis. CONCLUSION: The HSI method provides a non
      contact, non-invasive, intraoperative imaging procedure without the use of a
      contrast medium, which enables a real-time analysis of physiological anastomotic
      parameters, which may contribute to determine the "ideal" anastomotic region. In
      light of this, the establishment of this methodology in the field of visceral
      surgery, enabling the generation of normal or cut off values for different
      gastrointestinal anastomotic types, is an obvious necessity.

PMID- 29637247
TI  - [Early stage carcinoma in the hepatopancreaticobiliary region].

PMID- 29637248
TI  - ?

PMID- 29637249
TI  - The location of the peroneus longus tendon in the cuboid groove: sonographic
      study in various positions of the ankle-foot in asymptomatic volunteers.
AB  - OBJECTIVE: To evaluate the normal location of the peroneus longus tendon (PL) in
      the cuboid groove in various ankle-foot positions by ultrasonography in
      asymptomatic volunteers. MATERIALS AND METHODS: Ultrasonographic assessment of
      the PL in the cuboid groove was performed in 20 feet of ten healthy volunteers.
      Each PL was examined in five ankle-foot positions (i.e., neutral, dorsiflexion,
      plantar-flexion, supination, and pronation). The PL location was qualitatively
      categorized as "inside" when the PL was entirely within the cuboid groove, as
      "overlying" when some part of the PL was perched on the cuboid tuberosity, and as
      "outside" when the PL was entirely on the cuboid tuberosity. For quantitative
      evaluation of the PL location, the distance between the PL and the cuboid groove
      was measured. The width of the cuboid groove was measured in the neutral
      position. RESULTS: The PL location did not significantly change with changes in
      the ankle-foot position. Qualitatively, an "overlying" PL was the most common
      type, regardless of the ankle-foot position. "Inside" PLs were found in only 35,
      20, 30, 25, and 35% of feet in neutral, dorsiflexion, plantar-flexion,
      supination, and pronation positions, respectively. The quantitative PL location
      was also not significantly different among all ankle-foot positions and it was
      significantly negatively correlated with the cuboid groove width. CONCLUSIONS: In
      healthy volunteers, 65% or more of the PLs were partially or completely located
      outside of the cuboid groove, regardless of the ankle-foot position. The PL
      location relative to the cuboid groove was related to the cuboid groove width.

PMID- 29637250
TI  - Verticality perception reveals a vestibular deficit in adolescents with
      idiopathic scoliosis.
AB  - Adolescent idiopathic scoliosis (AIS) is a three-dimensional spine deformation
      with elusive aetiopathogenesis. One appealing hypothesis points to its neurologic
      origin with an emphasis on a vestibular impairment. In the present study, we
      explored the hypothesis of a vestibular deficit accompanying AIS by assessing
      differences in the subjective estimation of the gravitational vertical between
      adolescents with idiopathic scoliosis (n = 10, age 11-16 years, Cobb's angle > 15
      degrees ) and healthy age-matched controls (n = 10). Group participants actively
      controlled the verticality of a visual line in two visual conditions (eyes open
      visual feedback and eyes closed-no visual feedback) and using three different
      segments (hand, head, and trunk). An electromagnetic tracking sensor (Nest of
      Birds, Ascension Ltd., USA, 60 Hz), attached either to a hand-held rod, the head,
      or the upper trunk, measured the line's deviation from the gravitational vertical
      that was reflected in two measures, the mean absolute and variable error. The
      head's medio-lateral tilt when estimating verticality with the hand was also
      registered. Analysis revealed that adolescents with idiopathic scoliosis made a
      greater error than control participants when estimating verticality with the head
      and eyes closed. In addition, they adopted a significantly greater head tilt when
      estimating the vertical by controlling the hand-held rod, regardless of the
      availability of vision. The error in the earth vertical was greater when the
      estimate was performed in the absence of vision. Results suggest a malfunction of
      the vestibular system and/or a sensorimotor integration impairment in patients
      with AIS, while vision compensates for the observed deficit in estimating the
      earth vertical.

PMID- 29637251
TI  - Proteomic approaches beyond expression profiling and PTM analysis.
AB  - Essentially, all cellular functions are executed by proteins. Different
      physiological and pathological conditions dynamically control various properties
      of proteins, including expression levels, post-translational modifications
      (PTMs), protein-protein interactions, enzymatic activity, etc. Thus far, the vast
      majority of proteomic efforts have been focused on quantitative profiling of
      protein abundance/expression and their PTMs. In this article, we review some
      recent exciting progress in the development of proteomic approaches to examine
      protein functions from perspectives other than expression levels and PTMs.
      Specifically, we discuss advancements in proximity-based labeling, analysis of
      protein termini and newly synthesized proteins, and activity-based protein
      profiling.

PMID- 29637253
TI  - A Shift in Focus.

PMID- 29637254
TI  - [Paraneoplastic syndromes in rheumatology].
AB  - Rheumatic paraneoplastic syndromes are paraneoplastic arthritis, palmar fasciitis
      and polyarthritis syndrome, remitting seronegative symmetrical synovitis with
      pitting edema, pancreatic panniculitis with polyarthritis, paraneoplastic
      vasculitis, cancer-associated myositis, hypertrophic osteoarthropathy (Marie
      Bamberger disease) and tumor-induced osteomalacia. Typical clinical
      manifestations, pathogenesis, prognosis, and treatment of this entity are
      presented. Knowledge of these disease entities can lead to timely diagnosis of
      the underlying malignant disease and to a higher probability of a cure. Response
      of the paraneoplastic inflammatory manifestations to corticosteroids, non
      steroidal anti-inflammatory drugs or immunosuppressants is often insufficient.
      Curative removal of the malignant disease is crucial for the course of the
      paraneoplastic syndrome. When a paraneoplastic etiology of rheumatic symptoms is
      suspected, a step-wise diagnostic strategy is advisable.

PMID- 29637255
TI  - OCTA vessel density changes in the macular zone in glaucomatous eyes.
AB  - PURPOSE: To evaluate whether macular optical coherence tomography angiography
      (OCTA) can detect altered vessel density (VD) in the superficial and deep
      vascular plexus in glaucomatous eyes and to compare the diagnostic utility of the
      individual VD parameters. METHODS: The macular VD of 135 eyes, comprising 85 eyes
      diagnosed with glaucoma and 50 healthy control eyes, was examined using two OCTA
      devices (AngioPlex-Zeiss Meditec, Inc., Dublin, CA, USA, and AngioVue-OptoVue,
      Inc., Fremont, CA, USA). All study participants had neither vascular pathology,
      diabetes, nor vasoactive medication. The macular VD was measured at two different
      levels of segmentation (superficial [SL] and deep [DL] retinal vascular plexus)
      with a 6 * 6-mm macula scan, and VD was correlated with various structural and
      functional measurements. In order to test the accuracy of differentiation between
      eyes with and without glaucoma, we calculated the receiver operating
      characteristic (ROC) curve and the area under the curve (AUC). RESULTS: Macular
      VD was significantly lower in both SL and DL in glaucomatous eyes than in healthy
      eyes (p = SL < 0.0001; DL = 0.009). There was no significant difference in VD
      between the SL and the DL (p = 6.60 . 10-18). The greatest reduction of VD in
      glaucomatous eyes was found in the inferior macular sector. There was no
      correlation of VD with age or refractive error but moderate to high correlation
      with intraocular pressure, time of initial diagnosis, mean deviation, ganglion
      cell complex, peripapillary retinal nerve fiber layer thickness, cup to disc
      ratio, and rim area. Among the 14 individual features of macular VD, whole VD in
      the SL had the best diagnostic accuracy (77.6%) as measured by the area under the
      ROC. CONCLUSION: OCTA detects glaucomatous damage by measuring the macular vessel
      density in the superficial and deep retinal vascular plexus. It can be an
      additional diagnostic tool to detect glaucoma independently of the optic nerve.

PMID- 29637252
TI  - FDG-PET/CT(A) imaging in large vessel vasculitis and polymyalgia rheumatica:
      joint procedural recommendation of the EANM, SNMMI, and the PET Interest Group
      (PIG), and endorsed by the ASNC.
AB  - Large vessel vasculitis (LVV) is defined as a disease mainly affecting the large
      arteries, with two major variants, Takayasu arteritis (TA) and giant cell
      arteritis (GCA). GCA often coexists with polymyalgia rheumatica (PMR) in the same
      patient, since both belong to the same disease spectrum. FDG-PET/CT is a
      functional imaging technique which is an established tool in oncology, and has
      also demonstrated a role in the field of inflammatory diseases. Functional FDG
      PET combined with anatomical CT angiography, FDG-PET/CT(A), may be of synergistic
      value for optimal diagnosis, monitoring of disease activity, and evaluating
      damage progression in LVV. There are currently no guidelines regarding PET
      imaging acquisition for LVV and PMR, even though standardization is of the utmost
      importance in order to facilitate clinical studies and for daily clinical
      practice. This work constitutes a joint procedural recommendation on FDG
      PET/CT(A) imaging in large vessel vasculitis (LVV) and PMR from the
      Cardiovascular and Inflammation & Infection Committees of the European
      Association of Nuclear Medicine (EANM), the Cardiovascular Council of the Society
      of Nuclear Medicine and Molecular Imaging (SNMMI), and the PET Interest Group
      (PIG), and endorsed by the American Society of Nuclear Cardiology (ASNC). The aim
      of this joint paper is to provide recommendations and statements, based on the
      available evidence in the literature and consensus of experts in the field, for
      patient preparation, and FDG-PET/CT(A) acquisition and interpretation for the
      diagnosis and follow-up of patients with suspected or diagnosed LVV and/or PMR.
      This position paper aims to set an internationally accepted standard for FDG
      PET/CT(A) imaging and reporting of LVV and PMR.

PMID- 29637256
TI  - Behavioral, emotional and social functioning in children born with congenital
      diaphragmatic hernia.
AB  - PURPOSE: The aim was to investigate social competence and behavioral and
      emotional problems in children and adolescents born with CDH. METHODS: All
      children born with CDH, treated in Stockholm 1990-2009, were invited to
      participate. After written consent, the Child Behavior Checklist or Adult Self
      Report questionnaires were sent to participants. Of the 145 long-term survivors,
      51% returned a completed questionnaire. Both the syndrome and competence scales
      were used and open-ended questions were analyzed with manifest content analysis.
      RESULTS: All parents of children aged 1.5-5 years and 90% of parents of children
      aged 6-18 years reported a normal range on the syndrome scale. Five parents
      indicated internalizing, but none externalizing behavior. All young adults
      achieved a normal score on the syndrome scale. Eighty-five percent had normal
      school achievement, 79% had normal social scores and 40% had normal activity
      levels. Significantly fewer boys (23%) were in the normal activity range compared
      with 67% of girls. CONCLUSIONS: The vast majority of all parents of children born
      with CDH scored no behavioral or emotional problems, furthermore, they reported
      normal social and school competence. However, the activity levels seemed to be
      reduced in children born with CDH.

PMID- 29637258
TI  - Spatial transformation abilities and their relation to later mathematics
      performance.
AB  - Using a longitudinal approach, this study investigated the relational structure
      of different spatial transformation skills at kindergarten age, and how these
      spatial skills relate to children's later mathematics performance. Children were
      tested at three time points, in kindergarten, first grade, and second grade (N =
      119). Exploratory factor analyses revealed two subcomponents of spatial
      transformation skills: one representing egocentric transformations (mental
      rotation and spatial scaling), and one representing allocentric transformations
      (e.g., cross-sectioning, perspective taking). Structural equation modeling
      suggested that egocentric transformation skills showed their strongest relation
      to the part of the mathematics test tapping arithmetic operations, whereas
      allocentric transformations were strongly related to Numeric-Logical and Spatial
      Functions as well as geometry. The present findings point to a tight connection
      between early mental transformation skills, particularly the ones requiring a
      high level of spatial flexibility and a strong sense for spatial magnitudes, and
      children's mathematics performance at the beginning of their school career.

PMID- 29637257
TI  - Accuracy and impact of prenatal diagnosis in infants with omphalocele.
AB  - BACKGROUND: Associated anomalies in omphalocele are common, but to which extent
      these anomalies are diagnosed before or after birth is less well documented. AIM:
      To investigate the different types of associated anomalies, long-term survival
      and the extent whether these are diagnosed pre- or postnatally in children with a
      prenatal diagnosis of omphalocele at a single institution. MATERIALS AND METHODS:
      Retrospective review of all pregnancies with omphalocele managed and/or born at
      our institution between 2006 and 2016. RESULTS: A total of 42 cases with
      prenatally diagnosed omphalocele were identified. Of those 14 (31%) decided to
      terminate the pregnancy (TOP). Of the remaining 28 that continued, 12 were giant
      omphaloceles. The overall mortality rate was 18, 25% for giant and 12% for non
      giant omphaloceles. 64% had associated anomalies. Only 1/3 of these anomalies is
      diagnosed prenatally. CONCLUSION: The rate of associated malformations that are
      diagnosed postnatally is high, but the majority was malformations with a minor
      clinical significance or impact on future health. Beckwith-Wiedemann syndrome was
      present only in cases of non-giant omphalocele in our cohort.

PMID- 29637259
TI  - The protective effects of acute cardiovascular exercise on the interference of
      procedural memory.
AB  - Numerous studies have reported a positive impact of acute exercise for procedural
      skill memory. Previous work has revealed this effect, but these findings are
      confounded by a potential contribution of a night of sleep to the reported
      exercise-mediated reduction in interference. Thus, it remains unclear if exposure
      to a brief bout of exercise can provide protection to a newly acquired motor
      memory. The primary objective of the present study was to examine if a single
      bout of moderate-intensity cardiovascular exercise after practice of a novel
      motor sequence reduces the susceptibility to retroactive interference. To address
      this shortcoming, 17 individuals in a control condition practiced a novel motor
      sequence that was followed by test after a 6-h wake-filled interval. A separate
      group of 17 individuals experienced practice with an interfering motor sequence
      45 min after practice with the original sequence and were then administered test
      trials 6 h later. One additional group of 12 participants was exposed to an acute
      bout of exercise immediately after practice with the original motor sequence but
      prior to practice with the interfering motor sequence and the subsequent test. In
      comparison with the control condition, increased response times were revealed
      during the 6-h test for the individuals that were exposed to interference. The
      introduction of an acute bout of exercise between the practice of the two motor
      sequences produced a reduction in interference from practice with the second task
      at the time of test, however, this effect was not statistically significant.
      These data reinforce the hypothesis that while there may be a contribution from
      exercise to post-practice consolidation of procedural skills which is independent
      of sleep, sleep may interact with exercise to strengthen the effects of the
      latter on procedural memory.

PMID- 29637261
TI  - Dr. Edward Hacskaylo: a memoir and tribute.
AB  - Edward Hacskaylo was a pioneer in many aspects of mycorrhiza research and
      significantly influenced our understanding of the physiology and ecology of
      mycorrhizas. This memoir highlights Dr. Hacskaylo's many contributions and his
      impact on mycorrhiza research, especially through his encouragement and mentoring
      of young scientists.

PMID- 29637262
TI  - Radiofrequency needle for transseptal puncture is associated with lower incidence
      of thromboembolism during catheter ablation of atrial fibrillation: propensity
      score-matched analysis.
AB  - Atrial fibrillation (AF) ablation requires transseptal puncture to access the
      left atrium. Recently, a radiofrequency (RF) needle was developed. The purpose of
      this study was to compare the incidence of MRI-confirmed acute cerebral embolism
      (ACE) during AF ablation procedures performed with RF needle versus mechanical
      needle transseptal puncture. This study consisted of 383 consecutive patients who
      underwent catheter ablation for AF that required transseptal puncture with
      mechanical or radiofrequency transseptal needles. Of those, 232 propensity score
      matched patients (116 with each needle type) were included in the analysis. All
      patients had cerebral MRI performed 1 or 2 days after the procedure. Baseline
      characteristics were similar between the two groups. Total procedure time was
      significantly shorter in Group RF than Group non-RF (167 +/- 50 vs. 181 +/- 52
      min, P = 0.01). ACE was detected by MRI in 59 (25%) patients. All patients with
      ACE were asymptomatic. Incidence of ACE was lower in Group RF than Group non-RF
      (19 vs. 32%, P = 0.02). B-type natriuretic peptide level was higher in the
      patients with ACE as compared to those without ACE (65.2 +/- 68.7 vs. 44.7 +/-
      55.1 pg/ml, P = 0.02). In multivariable analysis, the use of RF needle and BNP
      level was related to the incidence of ACE (OR = 0.499, 95% CI 0.270-0.922, P =
      0.03 and OR = 1.005, 95% CI 1.000-1.010, P = 0.03). Use of RF needle for
      transseptal puncture was associated with lower total procedure time and risk of
      ACE during catheter ablation of AF.

PMID- 29637264
TI  - Requesting spinal MRIs effectively from primary care referrals.
AB  - OBJECTIVE: To define if MRI scans can accurately be requested based on
      information provided in the primary care referral and, therefore, streamline the
      patient journey. The demand for outpatient spinal appointments significantly
      exceeds our services' ability to provide efficient, high-quality patient care.
      Currently, magnetic resonance imaging (MRI) of the spine is requested following
      first consultation. METHODS: During routine vetting of primary care referral
      letters, three consultant spinal surgeons recorded how likely they thought each
      patient would be to have an MRI scan. Following the first consultation with the
      spinal service, the notes of each patient were reviewed to see if an MRI was
      requested. We measured the positive predictive value (PPV), negative predictive
      value (NPV), sensitivity and specificity of ordering MRI scans based on primary
      care referral letters. RESULTS: 149 patients were included [101 females, 48
      males, mean age 49 (16-87)]. There were 125 routine, 21 urgent, and 3 'urgent
      suspected cancer' referrals. The PPV of ordering MRIs before first consultation
      was 84%, NPV was 56% with the sensitivity and specificity being 82 and 59%,
      respectively. Ordering MRIs during initial vetting could shorten the patient
      journey with potential socioeconomic benefits. CONCLUSIONS: MRI scans can be
      effectively ordered based on the information provided by the primary care
      referral letter. Requesting MRI scans early in the patient journey can save
      considerable time, improve care, and deliver cost savings. These slides can be
      retrieved under Electronic Supplementary Material.

PMID- 29637263
TI  - Mining of favorable alleles for lodging resistance traits in rice (oryza sativa)
      through association mapping.
AB  - MAIN CONCLUSION: Fourteen new quantitative trait loci (QTLs) and ten favorable
      alleles were identified for lodging resistance traits in a natural population of
      rice. Parental combinations were designed to improve lodging resistance. Lodging
      is one of the most critical constraints to rice yield, and therefore, mining
      favorable alleles for lodging resistance traits is imperative for the advancement
      of cultivated rice and selection for market demand. This investigation was
      performed on a selected sample of 521 rice cultivars using 262 SSR markers in
      2016 and 2017. Lodging resistance traits were evaluated by plant height (PH),
      stem length (SL), stem diameter (SD), anti-thrust per stem (AT/S), and stem index
      (SI), with AT/S, used as the lodging resistance index. A genome-wide association
      map was generated by combining phenotypic and genotypic data. Eight
      subpopulations were found by structure software, and the linkage disequilibrium
      (LD) ranged from 30 to 80 cM. Identification of 68 marker-trait associations
      (MTAs) linking in 64 SSR markers for five traits was done. QTL were detected,
      including 15 for PH, 14 for SL, 14 for SD, 7 for AT/S, and 18 for SI. A number of
      favorable alleles were also discovered, including 22, 24, 19, 12, and 28 alleles
      for PH, SL, SD, AT/S, and SI, respectively. These favorable alleles might be used
      to design parental combinations, and the predictable results found by relieving
      the favorable alleles per QTL. The accessions containing favorable alleles for
      lodging resistant traits mined in this study could be useful for breeding
      superior rice cultivars.

PMID- 29637260
TI  - 90 years of monoamine oxidase: some progress and some confusion.
AB  - It would not be practical to attempt to deal with all the advances that have
      informed our understanding of the behavior and functions of this enzyme over the
      past 90 years. This account concentrates key advances that explain why the
      monoamine oxidases remain of pharmacological and biochemical interest and on some
      areas of continuing uncertainty. Some issues that remain to be understood or are
      in need of further clarification are highlighted.

PMID- 29637266
TI  - Implementation of medical scribes in an academic urology practice: an analysis of
      productivity, revenue, and satisfaction.
AB  - PURPOSE: Pressure on physicians to increase productivity is rising in parallel
      with administrative tasks, regulations, and the use of electronic health records
      (EHRs). Physician extenders and clinical pathways are already in use to increase
      productivity and reduce costs and burnout, but other strategies are required. We
      evaluated whether implementation of medical scribes in an academic urology clinic
      would affect productivity, revenue, and patient/provider satisfaction. METHODS:
      Six academic urologists were assigned scribes for 1 clinic day per week for 3
      months. Likert-type patient and provider surveys were developed to evaluate
      satisfaction with and without scribes. Matched clinic days in the year prior were
      used to evaluate changes in productivity and physician/hospital charges and
      revenue. RESULTS: After using scribes for 3 months, providers reported increased
      efficiency (p value = 0.03) and work satisfaction (p value = 0.03), while seeing
      a mean 2.15 more patients per session (+ 0.96 return visits, + 0.99 new patients,
      and + 0.22 procedures), contributing to an additional 2.6 wRVUs, $542 in
      physician charges, and $861 in hospital charges per clinic session. At a gross
      collection rate of 36%, actual combined revenue was + $506/session, representing
      a 26% increase in overall revenue. At a cost of $77/session, the net financial
      impact was + $429 per clinic session, resulting in a return-to-investment ratio
      greater than 6:1, while having no effect on patient satisfaction scores.
      Additionally, with scribes, clinic encounters were closed a mean 8.9 days
      earlier. CONCLUSIONS: Implementing medical scribes in academic urology practices
      may be useful in increasing productivity, revenue, and provider satisfaction,
      while maintaining high patient satisfaction.

PMID- 29637267
TI  - Dose reduction in abdominal CT: The road to submillisievert imaging.
AB  - This editorial comment refers to the article: Can We Perform CT of the Appendix
      with Less than 1 mSv? A De-escalating Dose-simulation Study. Park JH, et al., Eur
      Radiol, Dec 7, 2017.

PMID- 29637265
TI  - Genotype imputation performance of three reference panels using African ancestry
      individuals.
AB  - Genotype imputation estimates unobserved genotypes from genome-wide makers, to
      increase genome coverage and power for genome-wide association studies.
      Imputation has been successful for European ancestry populations in which very
      large reference panels are available. Smaller subsets of African descent
      populations are available in 1000 Genomes (1000G), the Consortium on Asthma among
      African ancestry Populations in the Americas (CAAPA) and the Haplotype Reference
      Consortium (HRC). We compared the performance of these reference panels when
      imputing variation in 3747 African Americans (AA) from two cohorts (HCV and
      COPDGene) genotyped using Illumina Omni microarrays. The haplotypes of 2504
      (1000G), 883 (CAAPA) and 32,470 individuals (HRC) were used as reference. We
      compared the number of variants, imputation quality, imputation accuracy and
      coverage between panels. In both cohorts, 1000G imputed 1.5-1.6* more variants
      than CAAPA and 1.2* more than HRC. Similar findings were observed for variants
      with imputation R2 > 0.5 and for rare, low-frequency, and common variants. When
      merging imputed variants of the three panels, the total number was 62-63 M with
      20 M overlapping variants imputed by all three panels, and a range of 5-15 M
      variants imputed exclusively with one of them. For overlapping variants,
      imputation quality was highest for HRC, followed by 1000G, then CAAPA, and
      improved as the minor allele frequency increased. 1000G, HRC and CAAPA provided
      high performance and accuracy for imputation of African American individuals,
      increasing the number of variants available for subsequent analyses. These panels
      are complementary and would benefit from the development of an integrated African
      reference panel.

PMID- 29637268
TI  - Proteomic pattern of implantative human endometrial fluid in in vitro
      fertilization cycles.
AB  - PURPOSE: To assess whether there are proteins in endometrial fluid aspirate (EFA)
      that predict implantation. METHODS: The population under study consisted of 285
      women undergoing embryo transfer (ET). Endometrial fluid aspiration was performed
      immediately before ET. Results of proteomic analysis of EFA were compared between
      33 cases who achieved pregnancy and 33 who did not. Samples were analysed by 2D
      electrophoresis and mass spectrometry. Blood samples were studied by ELISA
      Pregnancy rates and maternal complications were compared to those in women
      refusing aspiration. RESULTS: We found 23 proteins differentially expressed in
      the EFA in conception cycles: 4 up-regulated proteins and 19 down-regulated (FC =
      0.31 0.78) (among others, arginase-1, actin B, PARK-7, cofilin-1, stathmin,
      annexin-2 and CAPZB). Among the five studied proteins that were differentially
      expressed in EFA, none was differentially expressed in serum. The aspiration
      procedure had no impact on pregnancy rate. No maternal complications were
      reported. CONCLUSIONS: We found a very different protein profile in implantative
      cycles, the majority of proteins being down-regulated. This probably reflects a
      different endometrial functional status, more favourable to implantation. EFA
      proteomic analysis could be a useful tool in the planning ET strategies.

PMID- 29637269
TI  - Study on the effects of an oral lactobacilli and lactoferrin complex in women
      with intermediate vaginal microbiota.
AB  - PURPOSE: In the vagina of healthy reproductive-aged women, several microbial
      species maintain a finely tuned mutualistic relationship with the host providing
      the first-line of defense against the colonization by opportunistic pathogens,
      which are the leading cause of dysbiosis or vaginal infections (bacterial
      vaginosis, vulvovaginal candidiasis, and aerobic vaginitis). The use of probiotic
      lactobacilli to prevent vaginal infections has a good rationale, and an excellent
      safety record, but so far only a few strains have been clinically proven to be
      effective, particularly to prevent BV. The aim of the clinical trial was to
      evaluate the changes in Nugent score in women with intermediate vaginal
      microbiota treated with oral Lactobacillus acidophilus GLA-14 and Lactobacillus
      rhamnosus HN001 mixture, in combination with bovine lactoferrin RCXTM
      (Respecta(r)) or placebo, for 15 days. METHODS: Vaginal swabs were collected from
      each woman at baseline and at the end of probiotic treatment and analyzed by RT
      PCR. Both symptoms of abnormal vaginal micorbiota and adverse effects were
      assessed throughout the study. RESULTS: The results showed that oral intake of
      lactobacilli/lactoferrin mixture led to significant vaginal colonization by L.
      acidophilus GLA-14 and L. rhamnosus HN001 showing that both strains can colonize
      vagina following oral ingestion. The effect of such colonization is correlated
      with the restoration of normal Nugent score (values 0-3) and an improvement of
      symptoms of abnormal vaginal micorbiota including itching and discharge.
      CONCLUSIONS: Oral consumption of lactobacilli/lactoferrin complex corroborates
      the effectiveness of using lactobacilli for supporting vaginal health and
      provides a rational basis for future studies on vaginal infections.

PMID- 29637271
TI  - Correction to: Systematic assessment of urinary hydroxy-oxo-glutarate for
      diagnosis and follow up of primary hyperoxaluria type III.
AB  - The unit of the HOG-creatinine ratio presented in this article is calculated in
      MUmol/mg creatinine instead of the demonstrated unit of MUmol/MUmol. This applies
      to the parameter in the text of the article and the labeling of Figs. 1, 2b and
      3c.

PMID- 29637270
TI  - Dual JAK1 and STAT3 mutations in a breast implant-associated anaplastic large
      cell lymphoma.

PMID- 29637272
TI  - COQ2 nephropathy: a treatable cause of nephrotic syndrome in children.
AB  - BACKGROUND: Nephrotic syndrome can be caused by a subgroup of mitochondrial
      diseases classified as primary coenzyme Q10 (CoQ10) deficiency. Pathogenic COQ2
      variants are a cause of primary CoQ10 deficiency and present with phenotypes
      ranging from isolated nephrotic syndrome to fatal multisystem disease. CASE
      DIAGNOSIS/TREATMENT: We report three pediatric patients with COQ2 variants
      presenting with nephrotic syndrome. Two of these patients had normal leukocyte
      CoQ10 levels prior to treatment. Pathologic findings varied from mesangial
      sclerosis to focal segmental glomerulosclerosis, with all patients having
      abnormal appearing mitochondria on kidney biopsy. In two of the three patients
      treated with CoQ10 supplementation, the nephrotic syndrome resolved; and at
      follow-up, both have normal renal function and stable proteinuria. CONCLUSIONS:
      COQ2 nephropathy should be suspected in patients presenting with nephrotic
      syndrome, although less common than disease due to mutations in NPHS1, NPHS2, and
      WT1. The index of suspicion should remain high, and we suggest that providers
      consider genetic evaluation even in patients with normal leukocyte CoQ10 levels,
      as levels may be within normal range even with significant clinical disease.
      Early molecular diagnosis and specific treatment are essential in the management
      of this severe yet treatable condition.

PMID- 29637274
TI  - Biomarkers for traumatic brain injury.

PMID- 29637273
TI  - The Role of ADAR1 and ADAR2 in the Regulation of miRNA-21 in Idiopathic Pulmonary
      Fibrosis.
AB  - INTRODUCTION: microRNAs (miRNAs) are small non-coding 1RNAs that post
      transcriptionally regulate gene expression. Recent evidence shows that adenosine
      deaminases that act on RNA (ADAR) can edit miRNAs. miRNAs are involved in the
      development of different diseases, such as idiopathic pulmonary fibrosis (IPF).
      In IPF, about 40% of the miRNAs are differentially expressed with respect to
      controls. Among these miRNAs, miRNA-21 has been found over-expressed in IPF and
      its targets are anti-fibrosing molecules such as PELI1 and SPRY2. The objective
      of this study is to determine the role of ADAR1 and 2 on the expression of miRNA
      21 in human lung fibroblasts trough quantification of gene expression, protein
      levels, and overexpression of ADAR1 and 2. METHODS: Six control and six fibrotic
      primary fibroblast cell cultures were used for RNA extraction, ADAR1, ADAR2,
      PELI1, SPRY2, miRNA-21, and pri-miRNA-21 expression was measured. Subsequently,
      two fibrotic fibroblast cultures were used for overexpression of ADAR1 and ADAR2,
      and they were stimulated with TGFbeta1. Real-time PCR and Western blot were
      performed. RESULTS: ADAR1 is significantly downregulated in IPF fibroblasts; the
      overexpression of ADAR1 and ADAR2 reestablishes the expression levels of miRNA
      21, PELI1, and SPRY2 in fibroblasts of patients with IPF. CONCLUSION: These
      changes in the processing of miRNAs have great value in pathology diagnosis,
      including lung diseases, and play an important role in the understanding of
      molecular mechanisms involved in the development of different pathologies, as
      well as representing new therapeutic targets.

PMID- 29637276
TI  - Combining ecosystem services assessment with structured decision making to
      support ecological restoration planning.
AB  - Accounting for ecosystem services in environmental decision making is an emerging
      research topic. Modern frameworks for ecosystem services assessment emphasize
      evaluating the social benefits of ecosystems, in terms of who benefits and by how
      much, to aid in comparing multiple courses of action. Structured methods that use
      decision analytic-approaches are emerging for the practice of ecological
      restoration. In this article, we combine ecosystem services assessment with
      structured decision making to estimate and evaluate measures of the potential
      benefits of ecological restoration with a case study in the Woonasquatucket River
      watershed, Rhode Island, USA. We partnered with a local watershed management
      organization to analyze dozens of candidate wetland restoration sites for their
      abilities to supply five ecosystem services-flood water retention, scenic
      landscapes, learning opportunities, recreational opportunities, and birds. We
      developed 22 benefit indicators related to the ecosystem services as well as
      indicators for social equity and reliability that benefits will sustain in the
      future. We applied conceptual modeling and spatial analysis to estimate indicator
      values for each candidate restoration site. Lastly, we developed a decision
      support tool to score and aggregate the values for the organization to screen the
      restoration sites. Results show that restoration sites in urban areas can provide
      greater social benefits than sites in less urban areas. Our research approach is
      general and can be used to investigate other restoration planning studies that
      perform ecosystem services assessment and fit into a decision-making process.

PMID- 29637275
TI  - The molecular characterisation of Cryptosporidium species in relinquished dogs in
      Great Britain: a novel zoonotic risk?
AB  - Surveillance was conducted to investigate the occurrence of protozoan parasites
      of the genus Cryptosporidium in dogs newly admitted to a dog rehoming charity in
      London, Great Britain. Voided faecal samples were collected from all new
      admissions between 2011 and 2012 during six separate 4-week sampling periods.
      Information on host signalment, including age, breed and reason for submission
      and faecal consistency, was collected. Polymerase Chain Reaction (PCR) targeting
      the 18S ribosomal RNA gene, confirmed by sequencing, was conducted on the faecal
      samples to detect Cryptosporidium genomic DNA and determine Cryptosporidium
      identity. In total, 677 dogs were included in the study. The prevalence of
      Cryptosporidium-positive faecal samples was 4.6% (31/676). There were positive
      samples in all of the six sampling periods. Cryptosporidium canis (n = 28), C.
      parvum (n = 2) and C. andersoni (n = 1) were identified. Sixty KDa glycoprotein
      (gp60) gene amplicon sequencing of the C. parvum samples identified genotypes
      IIaA17G1R1 and IIaA15G2R1 for the first time from a dog. There were no
      significant associations between signalment data and Cryptosporidium status.
      While this was a study of one rehoming shelter, the presence of the potentially
      zoonotic C. parvum and C. canis in dogs highlights a public health concern.
      Further research is needed to better understand the epidemiology and potential
      impacts of Cryptosporidium infection in dogs.

PMID- 29637277
TI  - Quantifying the Hydrological Effect of Permitted Water Abstractions across
      Spatial Scales.
AB  - Water abstraction from rivers and aquifers has considerable potential to alter
      flow regimes, thereby influencing the physical, chemical, and ecological well
      being of freshwater ecosystems. The economic and social benefits of abstraction
      need to be balanced against its potentially deleterious consequences for
      hydrologically-driven ecological functions, ecosystem services, cultural values,
      and recreation. In New Zealand, recent legislation states that limits for the use
      of water resources should be set for all waterbodies to manage the potential
      cumulative impacts of abstraction and reduce allocation of the hydrological
      resource in over-allocated catchments. These limits must comprise at least a
      predefined minimum flow (the flow at which all abstraction must cease) and a
      total allocation (the maximum rate of abstraction summed across upstream
      abstractions). Over-allocation occurs when the sum of all upstream abstractions
      exceeds the total allocation. A national database describing consents to abstract
      water was collated. A replicable, transferable, and objective method was applied
      to calculate total allocation at the national, catchment, and reach scales across
      the entire country. Total allocation for each catchment was expressed by mapping
      Weighted Allocation Impact; an index that integrates magnitude and spread of
      water resource allocation across entire catchments. Results show that existing
      consents have caused over-allocation in several catchments, prompting questions
      about how to reduce abstraction in these locations.

PMID- 29637278
TI  - Integrating Qualitative and Quantitative Methods in Participatory Modeling to
      Elicit Behavioral Drivers in Environmental Dilemmas: the Case of Air Pollution in
      Talca, Chile.
AB  - The aim of this paper is to contribute to the exploration of environmental
      modeling methods based on the elicitation of stakeholders' mental models. This
      aim is motivated by the necessity to understand the dilemmas and behavioral
      rationales of individuals for supporting the management of environmental
      problems. The methodology developed for this paper integrates qualitative and
      quantitative methods by deploying focus groups for the elicitation of the
      behavioral rationales of the target population, and grounded theory to code the
      information gained in the focus groups and to guide the development of a dynamic
      simulation model. The approach is applied to a case of urban air pollution caused
      by residential heating with wood in central Chile. The results show how the
      households' behavior interrelates with the governmental management strategies and
      provide valuable and novel insights into potential challenges to the
      implementation of policies to manage the local air pollution problem. The
      experience further shows that the developed participatory modeling approach
      allows to overcome some of the issues currently encountered in the elicitation of
      individuals' behavioral rationales and in the quantification of qualitative
      information.

PMID- 29637280
TI  - Six thousand papers already: "the outcome of a matter is better than its
      beginning...".

PMID- 29637279
TI  - Active pharmacovigilance in China: recent development and future perspectives.
AB  - BACKGROUND: The effectiveness of active pharmacovigilance depends on the specific
      methods adopted and the work patterns put into place. Over the past few years,
      much attention has been paid to the importance of implementing such systems in
      China. However, less has been done to evaluate the state of implementation and
      future needs of such systems. METHODS: This paper reviews China's recent
      approaches to active pharmacovigilance by examining: (1) information collected
      from scientific articles and the websites of the China Food and Drug
      Administration and the China National Center for Adverse Drug Reaction
      Monitoring, (2) information available on China's spontaneous reporting systems
      (SRS) and active pharmacovigilance system, and (3) annual reports and internal
      reports on this subject. RESULTS: Areas that improved most meaningfully for
      China's active pharmacovigilance in recent years appear to include: (1) quicker
      reporting and more intelligent scanning methods for adverse drug reactions
      (ADRs), (2) the use of pharmacovigilance approaches to mine electronic hospital
      records, and (3) the development of integrated systems including the China
      Hospital Pharmacovigilance System and China Sentinel Hospital Alliance Program.
      CONCLUSION: Not only has the national online SRS system provided a platform for
      passive pharmacovigilance, it has also become an important platform for various
      explorations of active pharmacovigilance in China. Quick reporting and
      intelligent scanning of ADRs, facilitated by automated ADR detection based on
      electronic hospital records, have accelerated to capabilities for active
      pharmacovigilance. The outcomes of the programs, such as the China Hospital
      Pharmacovigilance System and China Sentinel Hospital Alliance Program, usher in a
      new era for China's active pharmacovigilance. These are particularly important to
      bridge the information system of sentinel hospitals and ADR research centers, but
      gaps remain. Thus, much work needs to be done before a high-level active
      pharmacovigilance system is sufficiently mature to ensure drug safety in the
      country.

PMID- 29637281
TI  - Minimally invasive treatment for osteonecrosis of the femoral head with
      angioconductive bioceramic rod.
AB  - PURPOSE: To describe the rationale, the surgical technique, and the short-term
      follow-up results of a new minimally invasive treatment of osteonecrosis of the
      femoral head (ONFH) with an angioconductive bioceramic rod (ABR) implant.
      METHODS: Sixty-two patients (72 hips) with ARCO stage IIA-IIIC ONFH treated with
      the minimally invasive ABR from January 2012 to December 2016 were reviewed (17
      females, 45 males, mean age 44.49). This technique used the angioconductive
      properties of the porous implant to repair the necrosis by driving
      vascularization from the trochanter to the necrotic area. Patients had a mean
      follow-up period of 26.74 months. The outcomes were evaluated by hip joint
      survival, radiograph, and the Harris Hip Score (HHS). The complications occurred
      during the treatment period were recorded. RESULTS: No serious post-operative
      complications occurred during the treatment. The overall joint survival rate was
      90.27%, with seven conversions to THA. Improvements were observed in 23 (31.95%)
      hips, 24 (33.33%) hips remained stable, and 25 (34.72%) hips had worse results
      according to the radiographic evaluation. The mean HHS at the end follow-up
      significantly improved compared to the pre-operative mean HHS (82.27 vs 58.14, p
      < 0.001). In both radiographic evaluation and HHS, the treatment was more
      effective on patients beneath 44 years old (p < 0.05); ARCO stage II compared to
      stage III (p < 0.05); and China-Japan Friendship Hospital (CJFH) type C compared
      to CJFH type L (p < 0.05). CONCLUSIONS: The minimally invasive treatment of ONFH
      with ABR showed promising results in delaying or even terminating the progression
      of the necrosis and improving hip function, especially in younger patients and in
      the early stages of the disease.

PMID- 29637282
TI  - The efficacy and safety of multiple-dose oral tranexamic acid on blood loss
      following total hip arthroplasty: a randomized controlled trial.
AB  - PURPOSES: To explore the efficacy and safety of multiple-dose oral tranexamic
      acid (TXA) on blood loss following primary total hip arthroplasty (THA). METHODS:
      A total of 152 patients were randomized into three groups to receive 2 g of oral
      TXA two hours  pre-operatively (group A), or another bolus of 2 g of oral TXA
      four hours post-operatively (group B), or another three boluses of 2 g of oral
      TXA four, ten, and 16 hours post-operatively (group C). The primary outcomes were
      total blood loss (TBL), hidden blood loss (HBL), and transfusion rate. The
      secondary outcomes were haemoglobin (Hb) and haematocrit (Hct) drop, the level of
      fibrinolysis parameters (fibrin degradation products, D-dimer), and complications
      (thrombotic diseases, stroke, cardiac infarction, and infection). RESULTS: The
      mean TBL and HBL in group C were lower than those in group A (p < 0.001 and p <
      0.001) and group B (p = 0.012 and p = 0.029). The Hb drop on post-operative day
      one (POD1) and POD3 in group C was lower than those in group A (p < 0.001 and p =
      0.029) and group B (p < 0.001 and p = 0.004). The difference was similar
      regarding Hct drop on POD3 (p < 0.001 and p = 0.014). Moreover, fibrin
      degradation products and D-dimer in group C were lower than in groups A and B on
      POD1 and POD3 (p < 0.001 and p < 0.001). The incidence of complications such as
      venous thromboembolism did not differ significantly among the three groups (p >
      0.05). CONCLUSIONS: Multiple boluses of oral TXA could further reduce blood loss,
      Hb and Hct drop, and restrain post-operative fibrinolysis in primary THA without
      increasing the risk of complications. LEVEL OF EVIDENCE I: Therapeutic study.

PMID- 29637283
TI  - Results of the Latarjet coracoid bone block procedure performed by mini invasive
      approach.
AB  - INTRODUCTION: The coracoid block technique described by Latarjet was modified by
      Patte and Walch in order to increase the glenoid surface. Saragaglia further
      modified this technique and described a minimally invasive approach which allows
      faster post-operative recovery. The aim of this study was to evaluate the medium
      term functional and radiological results of this technique. METHODS: This is a
      single surgeon cohort of 40 shoulders in 38 patients (32 men, 6 women) with an
      average age of 34.5 years operated on between January and December 2014. The skin
      incision was 3 to 6 cm long allowing the bony block to be passed under the
      subscapularis tendon without sectioning it and to be placed in lying position.
      The bone block was fixed with a 6.5 cancellous screw or a 7.0 cannulated screw.
      RESULTS: At an average follow-up of 48 months, there were no recurrent
      dislocations. The average WOSI score was 42, the average Constant score was 95
      corrected to 97% and the average SSV was 97. Visual analogue scores were 0 at
      rest and 0.6 with activity. The bone block healed in 92.5% of cases. It was flush
      with the edge of the glenoid in 84% of cases, lateralised in 10% and medialised
      in 6% of cases. Mean internal rotation power was 12 kg in the operated shoulder
      compared with 9 kg in the non-operated shoulder. CONCLUSION: The treatment of
      recurrent anterior shoulder instability by mini invasive Latarjet gives excellent
      medium-term functional results. The rate of recurrent dislocation in this series
      was zero and internal rotation power was well preserved. This is an excellent
      alternative to arthroscopic procedures which are yet to demonstrate their
      superiority over open surgery.

PMID- 29637284
TI  - Social competence and psychopathology in early childhood: a systematic review.
AB  - The acquisition of social competence, such as showing prosocial behaviour
      (fulfilling others' needs) and social initiative (fulfilling own needs),
      constitutes one major developmental task in childhood and adolescence. Previous
      research suggests that in middle childhood, impaired social competences are
      related to childhood psychopathology, such as externalizing and internalizing
      disorders. As the period of preschool age is a particularly important time for
      both the development of social competence and early psychopathological symptoms,
      we conducted a systematic review to investigate the role of social competence in
      relation to early childhood psychopathology. Twenty-one clinical as well as
      subclinical studies published prior to September 2016 were included in a
      qualitative analysis of the relation between prosocial behaviour, social
      initiative, and early externalizing and internalizing symptoms in preschool age
      children (age 3-6). Effect sizes for each study were calculated if required
      information was available. Our review suggests that from early on in childhood
      development, externalizing symptoms are accompanied by prosocial behaviour
      deficits such as lower levels of helping or cooperating, whereas internalizing
      symptoms may be accompanied by either deficient or excessive levels of prosocial
      behaviour. Exhibiting social initiative such as initiating contact with others or
      communicating one's own needs seems to be impaired in children with internalizing
      symptoms. Implications for current theory and future research are discussed.

PMID- 29637286
TI  - The biogenesis of iron-sulfur proteins: from cellular biology to molecular
      aspects.

PMID- 29637285
TI  - Study of cytokinin transport from shoots to roots of wheat plants is informed by
      a novel method of differential localization of free cytokinin bases or their
      ribosylated forms by means of their specific fixation.
AB  - The aim of the present report was to demonstrate how a novel approach for
      immunohistochemical localization of cytokinins in the leaf and particularly in
      the phloem may complement to the study of their long-distance transport.
      Different procedures of fixation were used to conjugate either cytokinin bases or
      their ribosides to proteins of cytoplasm to enable visualization and differential
      localization of these cytokinins in the leaf cells of wheat plants. In parallel
      to immunolocalization of cytokinins in the leaf cells, we immunoassayed
      distribution of free bases of cytokinins, their nucleotides and ribosides between
      roots and shoots of wheat plants as well as their presence in phloem sap after
      incubation of leaves in a solution supplemented with either trans-zeatin or
      isopentenyladenine. The obtained data show ribosylation of the zeatin applied to
      the leaves and its elevated level in the phloem sap supported by in vivo
      localization showing the presence of ribosylated forms of zeatin in leaf vessels.
      This suggests that conversion of zeatin to its riboside is important for the
      shoot-to-root transport of zeatin-type cytokinins in wheat. Exogenous
      isopentenyladenine was not modified, but diffused from the leaves as free base.
      These metabolic differences may not be universal and may depend on the plant
      species and age. Although the measurements of cytokinins in the phloem sap and
      root tissue is the most defining for determining cytokinin transport, study of
      immunolocalization of either free cytokinin bases or their ribosylated forms may
      be a valuable source of information for predicting their transport in the phloem
      and to the roots.

PMID- 29637287
TI  - The effect of chronic stimulation of serotonin receptor type 7 on recognition,
      passive avoidance memory, hippocampal long-term potentiation, and neuronal
      apoptosis in the amyloid beta protein treated rat.
AB  - RATIONALE: Alzheimer's disease (AD) is a neurodegenerative disorder characterized
      by memory impairment, neuronal death, and synaptic loss in the hippocampus. Long
      term potentiation (LTP), a type of synaptic plasticity, occurs during learning
      and memory. Serotonin receptor type 7 (5-HTR7) activation is suggested as a
      possible therapeutic target for AD. OBJECTIVE: The aim of the present study was
      to examine the effects of chronic treatment with the 5-HTR7 agonist, AS19, on
      cognitive function, memory, hippocampal plasticity, amyloid beta (Abeta) plaque
      accumulation, and apoptosis in an adult rat model of AD. METHODS: AD was induced
      in rats using Abeta (single 1 MUg/MUL intracerebroventricular (icv) injection
      during surgery). The following experimental groups were included: control, sham
      operated, Abeta + saline (1 MUL icv for 30 days), and Abeta + AS19 (1 MUg/MUL icv
      for 30 days) groups. The animals were tested for cognition and memory performance
      using the novel object recognition and passive avoidance tests, respectively.
      Next, anesthetized rats were placed in a stereotaxic apparatus for electrode
      implantation, and field potentials were recorded in the hippocampal dentate
      gyrus. Lastly, brains were removed and Abeta plaques and neuronal apoptosis were
      evaluated using Congo red staining and TUNEL assay, respectively. RESULTS:
      Administration of AS19 in the Abeta rats increased the discrimination index of
      the novel object recognition test. Furthermore, AS19 treatment decreased time
      spent in the dark compartment during the passive avoidance test. AS19 also
      enhanced both the population spike (PS) amplitude and the field excitatory
      postsynaptic potential (fEPSP) slope evoked potentials of the LTP components.
      Abeta plaques and neuronal apoptosis were decreased in the AS19-treated Abeta
      rats. CONCLUSIONS: These results indicate that chronic treatment with a 5-HTR7
      agonist can prevent Abeta-related impairments in cognition and memory performance
      by alleviating Abeta plaque accumulation and neuronal apoptosis, hence improving
      neuronal plasticity. AS19 may be useful as a therapeutic agent for AD.

PMID- 29637288
TI  - Effects of cariprazine on extracellular levels of glutamate, GABA, dopamine,
      noradrenaline and serotonin in the medial prefrontal cortex in the rat
      phencyclidine model of schizophrenia studied by microdialysis and simultaneous
      recordings of locomotor activity.
AB  - RATIONALE: Aberrant glutamatergic, dopaminergic, and GABAergic neurotransmission
      has been implicated in schizophrenia. Cariprazine reverses the behavioral effects
      observed in the rat phencyclidine (PCP)-induced model of schizophrenia; however,
      little is known about its in vivo neurochemistry. OBJECTIVES: The study aims to
      compare the effects of cariprazine and aripiprazole on PCP-induced changes in the
      extracellular levels of glutamate, dopamine, serotonin, noradrenaline, and GABA
      in the rat medial prefrontal cortex (mPFC), and on locomotor activation. METHODS:
      Microdialysis was performed in awake rats with probes placed into the mPFC. Rats
      (n = 7/group) received vehicle (saline), cariprazine (0.05, 0.2, or 0.8 mg/kg),
      or aripiprazole (3 or 20 mg/kg) via gavage. After 60 min, 5 mg/kg PCP was
      administered intraperitoneally (i.p.). Samples were taken before drug
      administration, during pretreatment, and after PCP injection. Locomotor activity
      recording and microdialysis sampling occurred simultaneously. RESULTS: PCP
      treatment increased extracellular levels of all the neurotransmitters tested
      except GABA, for which there were no significant changes. Cariprazine and
      aripiprazole dose-dependently inhibited the PCP-induced increases of tested
      neurotransmitters. Overall effects were significant for higher cariprazine doses
      and both aripiprazole doses for glutamate and noradrenaline, for higher
      cariprazine doses and 20 mg/kg aripiprazole for dopamine, and for 0.8 mg/kg
      cariprazine and 20 mg/kg aripiprazole for serotonin and locomotor activity.
      CONCLUSION: Both cariprazine and aripiprazole dose-dependently attenuated PCP
      induced hyperlocomotion and acute increases in glutamate, dopamine,
      noradrenaline, and serotonin levels in the mPFC; cariprazine was approximately 5
      fold more potent than aripiprazole.

PMID- 29637289
TI  - Luteibacter pinisoli sp. nov., a casein degrading bacterium isolated from
      rhizospheric soil of Pinus koraiensis.
AB  - A yellow pigmented, Gram-staining negative, motile and rod-shaped novel bacterial
      strain, designated MAH-14T was isolated from rhizospheric soil and was
      characterized using a polyphasic approach. The isolated strain was aerobic,
      oxidase and catalase were positive, optimum growth temperature and pH were 28-30 
      degrees C and 6.5, respectively. The novel strain is able to hydrolyze casein,
      starch, esculin, gelatin, L-tyrosine, DNA, tween 80, tween 20, L-arginine and 4
      nitrophenyl-BD-galactopyranoside. On the basis of 16S rRNA gene sequence
      analysis, strain MAH-14T belongs to the genus Luteibacter and is most closely
      related to Luteibacter yeojuensis R2A16-10T (98.5%), Luteibacter anthropi CCUG
      25036T (98.4%) and Luteibacter rhizovicinus LJ96T (98.3%). In DNA-DNA
      hybridization experiments, the DNA relatedness between strain MAH-14T and its
      closest phylogenetic neighbor was below 45.0%. The predominant respiratory
      quinone and the DNA G + C content of the novel strain were ubiquinone-8 and 63.5
      mol%, respectively. The novel strain MAH-14T is able to produce flexirubin-type
      pigments. The major cellular fatty acids were C15:0 iso, summed feature 3 (C16:1
      omega7c and/or C16:1 omega6c) and summed feature 9 (C17:1 iso omega9c and/or
      C16:0 10-methyl). The DNA-DNA hybridization results and results of the genotypic
      analysis in combination with chemotaxonomic and physiological data revealed that
      strain MAH-14T represented a novel species within the genus Luteibacter, for
      which the name Luteibacter pinisoli, is proposed. The type strain is MAH-14T (=
      KACC 19298T = CGMCC 1.16227T).

PMID- 29637290
TI  - Strand-specific RNA-seq analysis of the Acidithiobacillus ferrooxidans
      transcriptome in response to magnesium stress.
AB  - Bioleaching is a promising process for 350 million tons Jinchuan low-grade
      pentlandite. But, Jinchuan pentlandite has lots of magnesium and high
      concentration of Mg2+ is harmful to bioleaching microorganisms. Thus, finding a
      way to improve the adaption of microorganisms to Mg2+ is a key for bioleaching.
      In the study, we found that oxidizing activity, bioleaching ability and biofilm
      formation of A.f were inhibited by Mg2+ stress. In addition, we analyzed mRNA and
      small RNA (sRNA) of Acidithiobacillus ferrooxidans (A.f) under Mg2+ stress by
      strand-specific RNA-sequencing (ssRNA-seq). After the bioinformatics process,
      2475 coding genes were obtained, and there were 33 differential expression genes
      (DEGs) in 0.1 M-VS-Con, including 28 down-regulated and 5 up-regulated, whereas
      52 DEGs were obtained in 0.5 M-VS-Con, including 28 down-regulated and 24 up
      regulated. Gene ontology analysis showed most of DEGs were involved in catalytic
      activity, metabolic process and single-organism process. Furthermore, we
      identified 636 sRNA and some differential expression sRNA that may respond to
      Mg2+ stress. Further analysis of DEGs suggested that Mg2+ stress reduced biofilm
      formation perhaps through inhibiting Type IV Pili-related gene expression and
      inhibited bacterial activity perhaps through affecting carbon fixation. The study
      provided the foundation to understand the mechanisms of Mg2+ resistance in A.f
      and may be helpful to improve bioleaching ability for pentlandit.

PMID- 29637291
TI  - Efficient methanol-degrading aerobic bacteria isolated from a wetland ecosystem.
AB  - Methylotrophs present in the soil play an important role in the regulation of one
      carbon compounds in the environment, and thereby aid in mitigating global
      warming. The study envisages the isolation and characterization of methanol
      degrading bacteria from Kuttanad wetland ecosystem, India. Three methylotrophs,
      viz. Achromobacter spanius KUT14, Acinetobacter sp. KUT26 and Methylobacterium
      radiotolerans KUT39 were isolated and their phylogenetic positions were
      determined by constructing a phylogenetic tree based on 16S rDNA sequences. In
      vitro activity of methanol dehydrogenase enzyme, responsible for methanol
      oxidation was evaluated and the genes involved in methanol metabolism, mxaF and
      xoxF were partially amplified and sequenced. The specific activity of methanol
      dehydrogenase (451.9 nmol min-1 mg-1) observed in KUT39 is the highest, reported
      ever to our knowledge from a soil bacterium. KUT14 recorded the least activity of
      50.15 nmol min-1 mg-1 and is the first report on methylotrophy in A. spanius.

PMID- 29637292
TI  - Response to the letter to the editor Systemic inflammatory response in pediatric
      central nervous system tumors.

PMID- 29637293
TI  - Season structures prokaryotic partners but not algal symbionts in subtropical
      hard corals.
AB  - Coral reef ecosystems have great economic, social, and ecological value. The
      ecological success of coral reef ecosystems critically depends on coral-algal
      symbiosis and coral-prokaryotic partnership. However, seasonal changes underlying
      these relationships in subtropical hard corals of Hong Kong are poorly studied.
      Here, we compared the community changes of algal symbionts and prokaryotic
      partners in Platygyra carnosa and Galaxea fascicularis from Hong Kong collected
      at two seasonal time points of winter and summer via massively parallel
      sequencing of genetic markers and multivariate analysis. The results indicated
      that algal symbionts showed no significant changes between the two seasonal time
      points but prokaryotic partners changed substantially. Prokaryotic partners
      putatively involved in photosynthesis, nitrogen fixation, and sulfur oxidation
      increased significantly from winter to summer, while prokaryotic partners
      potentially associated with chemosynthesis, ammonia oxidation, and nitrite
      oxidation decreased significantly from winter to summer. Dissolved oxygen and pH
      served as the main contributors influencing prokaryotic partners in winter, while
      temperature, turbidity, and salinity played a dominant role in shaping
      prokaryotic partners in summer. The findings of the present study suggest that
      season structures prokaryotic partners but not algal symbionts in subtropical
      hard corals.

PMID- 29637294
TI  - Enzymatic hydrolysis of rapeseed oil by Thermomyces lanuginosus lipase: variation
      of continuous and dispersed phase in a slug flow reactor.
AB  - This paper takes a look on the effects of mass transport limitation occurring in
      hydrolysis of rape seed oil by means of an interfacial activated lipase from
      Thermomyces lanuginosus. In order to carry out investigations for process
      optimization, the slug flow reactor was chosen in which a large interfacial area
      can be generated and the mass transport can be investigated individually for each
      phase. The choice of the capillary material determines the dispersed and the
      continuous phase. As shown by computational fluid dynamics simulation, the
      continuous phase is well mixed due to wall effects. The mixing patterns in the
      dispersed phase differ due to viscous forces between the phases. It was found
      that, at the same fluid velocities, the conversion in the glass capillary is
      higher than in the PTFE capillary. The surface-specific hydrolysis rate is used
      for comparison purposes, since the properties of the capillary are different.
      Increasing the velocity, the hydrolysis rate can be considerably increased in
      comparison to stagnant conditions. Already at a fluid velocity of 1 mm s-1, the
      hydrolysis rates increased to 2.3-fold in the glass capillary and moreover by a
      factor of 4 in the PTFE capillary.

PMID- 29637295
TI  - Second-site prosthetic joint infection in patients with multiple prosthetic
      joints.
AB  - INTRODUCTION: Prosthetic joint infections (PJIs) are among the most serious
      complications in arthroplasty. A second-site PJI in patients with multiple
      prosthetic joints increases morbidity, with many requiring further revision
      procedures. We aimed to establish why some patients with multiple joints develop
      second-site infections. METHODS: Our institution's arthroplasty database was
      reviewed from 2004 to 2017. All PJIs were identified, and all patients with more
      than one prosthetic joint in situ were included. We recorded risk factors,
      causative organisms, number of procedures and length of stay. RESULTS: Forty-four
      patients meeting the criteria were identified. Four patients (9.1%) developed
      second-site infection. Eight patients (18.2%) developed re-infection of the
      primary PJI. Positive MRSA carrier status and PJI of a total knee replacement
      were associated with an increased risk of a second episode of infection. Patients
      who developed further infection had more frequent admission and longer lengths of
      stay than isolated PJIs. DISCUSSION: Higher morbidity and use of hospital
      resources are associated with this cohort of patients. PJIs in total knee
      replacements and positive MRSA status are associated with higher rates of second
      infection. Identifying this vulnerable cohort of patients at an early stage is
      critical to ensure measures are taken to reduce the risks of further infection.

PMID- 29637296
TI  - Size-related shifts in carbon gain and growth responses to light differ among
      rainforest evergreens of contrasting shade tolerance.
AB  - Recent work suggests that plant size affects light requirements and carbon
      balance of juvenile trees, and such shifts may be greater in light-demanding
      species than in their more shade-tolerant associates. To explore the
      physiological basis of such shifts, we measured juvenile light interception,
      carbon gain and growth of four subtropical Australian rainforest trees differing
      in shade tolerance, comparing individuals ranging from 13 to 238 cm in height,
      across a wide range of understory environments. We hypothesized that even in a
      standardized light environment, increasing sapling size would lead to declines in
      net daily carbon gain of foliage and relative growth rates (RGR) of all species,
      with declines more pronounced in light-demanding species. Crown architecture of
      individuals was recorded using a 3-dimensional digitizer, and the YPLANT program
      was used to estimate the self-shaded fraction of each crown and model net carbon
      gain. Increased sapling size caused a significant increase in self-shading, and
      significant declines in net daily carbon gain and RGR of light-demanding species,
      while such ontogenetic variations were minimal or absent in shade-tolerant
      species. Additionally, differences in the slope of the relationship between light
      and RGR led to crossovers in RGR among shade-tolerant and light-demanding species
      at low light. Our results show that the magnitude of ontogenetic variation in net
      daily carbon gain and RGR can be substantial and may depend on successional
      status, making it unsafe to assume that young seedling performance can be used to
      predict or model responses of larger juvenile trees.

PMID- 29637297
TI  - Receivers matter: the meaning of alarm calls and competition for nest sites in a
      bird community.
AB  - Animal communities may constitute information networks where individuals gain
      information on predation risk by eavesdropping on alarm calls of other species.
      However, communities include species in different trophic levels, and it is not
      yet known how the trophic level of the receiver influences the informative value
      of a call. Furthermore, no empirical study has yet tested how increased
      competition may influence the value of alarm calls for distinct receivers. Here,
      we identify the importance of alarm calls emitted by a small owl, the little owl
      (Athene noctua), on the structure of a cavity-nesting bird community including
      mesopredators and primary prey under variable levels of competition for nest
      holes. Competitors sharing top predators with the callers and prey of the callers
      interpreted alarm and non-alarm calls differently. Competitors chose
      preferentially alarm and non-alarm patches over control patches to breed, while
      prey selected alarm patches. In contrast, competition for nest sites affected
      habitat selection of prey species more than that of competitors of the callers.
      This study provides support for a changing value of alarm calls and competition
      for nest sites for distinct receivers related to niche overlapping among callers
      and eavesdroppers, therefore, calling attention to possible cascading effects by
      the use of information in natural communities.

PMID- 29637298
TI  - Pattern separation in the hippocampus: distinct circuits under different
      conditions.
AB  - Pattern separation is a fundamental hippocampal process thought to be critical
      for distinguishing similar episodic memories, and has long been recognized as a
      natural function of the dentate gyrus (DG), supporting autoassociative learning
      in CA3. Understanding how neural circuits within the DG-CA3 network mediate this
      process has received much interest, yet the exact mechanisms behind remain
      elusive. Here, we argue for the case that sparse coding is necessary but not
      sufficient to ensure efficient separation and, alternatively, propose a possible
      interaction of distinct circuits which, nevertheless, act in synergy to produce a
      unitary function of pattern separation. The proposed circuits involve different
      functional granule-cell populations, a primary population mediates sparsification
      and provides recurrent excitation to the other populations which are related to
      additional pattern separation mechanisms with higher degrees of robustness
      against interference in CA3. A variety of top-down and bottom-up factors, such as
      motivation, emotion, and pattern similarity, control the selection of circuitry
      depending on circumstances. According to this framework, a computational model is
      implemented and tested against model variants in a series of numerical
      simulations and biological experiments. The results demonstrate that the model
      combines fast learning, robust pattern separation and high storage capacity. It
      also accounts for the controversy around the involvement of the DG during memory
      recall, explains other puzzling findings, and makes predictions that can inform
      future investigations.

PMID- 29637299
TI  - A Smooth Esophageal Stricture Causing Dysphagia.
AB  - Dysphagia in patients with lung cancer is usually due to direct invasion from
      bronchogenic carcinomas or nodal localizations, while metastases from distant
      lung neoplasms are considered rare. We report a case of a smooth esophageal
      narrowing secondary to intramural metastasis from pulmonary adenocarcinoma in a
      patient with no previous history of neoplasia. Since standard linear
      echoendoscope could not overpass the malignant stricture, we obtained a
      histological diagnosis by fine-needle aspiration biopsy using an echobronchoscope
      (EBUS), due to its lower diameter. The EBUS scope represents a valuable tool to
      obtain cytological specimens in patients with esophageal strictures.

PMID- 29637300
TI  - Single-Cell RNA-Sequencing in Glioma.
AB  - PURPOSE OF REVIEW: In this review, we seek to summarize the literature concerning
      the use of single-cell RNA-sequencing for CNS gliomas. RECENT FINDINGS: Single
      cell analysis has revealed complex tumor heterogeneity, subpopulations of
      proliferating stem-like cells and expanded our view of tumor microenvironment
      influence in the disease process. Although bulk RNA-sequencing has guided our
      initial understanding of glioma genetics, this method does not accurately define
      the heterogeneous subpopulations found within these tumors. Single-cell
      techniques have appealing applications in cancer research, as diverse cell types
      and the tumor microenvironment have important implications in therapy. High cost
      and difficult protocols prevent widespread use of single-cell RNA-sequencing;
      however, continued innovation will improve accessibility and expand our of
      knowledge gliomas.

PMID- 29637301
TI  - [Bilateral corneal calcification in ocular graft-versus-host disease].

PMID- 29637303
TI  - [Ophthalmologic healthcare utilization of people in need of long-term care :
      Analyses of health insurance data of the AOK Baden-Wurttemberg].
AB  - INTRODUCTION: Eye diseases causing visual impairment increase with age. Thus,
      seeking eye care has a higher probability in older people. In this study, the
      rate of utilization of outpatient eye care services in Germany was analyzed. The
      analyses focused on older persons and persons in need of either home-based or
      facility-based long-term care. METHODS: A descriptive secondary data analysis of
      health insurance data of the AOK Baden-Wurttemberg from 2016 was conducted. The
      study population comprised all insured persons on 1 January 2016. The cohort of
      older persons (60 years+) was further stratified by the type of care (home
      based/facility-based) and the level of care (0-3). The utilization of outpatient
      eye care services was defined by the reimbursement for an ophthalmologist's
      provision of service. RESULTS: While 39.3% of the study population 60+ years old
      sought eye care, the utilization rate was lower among people in need of home
      based (33.0%) and facility-based care (19.3%). The utilization rates showed
      comparable age-dependent patterns, except for persons in need of facility-based
      care where rates were similar for all age groups. Utilization rates were
      negatively associated with increasing care levels. Only people with care level 0
      showed lower utilization rates than people with care level 1. DISCUSSION:
      Utilization rates of eye healthcare services among older persons are considerably
      influenced by the need of long-term care, by the form of care as well as by the
      level of care.

PMID- 29637302
TI  - [Treated cases of retinopathy of prematurity in Germany : 5-year data from the
      Retina.net ROP registry].
AB  - BACKGROUND: Retinopathy of prematurity (ROP) is one of the main reasons for
      childhood blindness. The number of infants requiring treatment, however, is low
      for individual centers. The Retina.net ROP registry has been founded to allow a
      joint analysis of treatment patterns and courses post treatment. OBJECTIVE: This
      paper reports treatment patterns over 5 years. MATERIAL AND METHODS: All infants
      born between January 2011 and December 2015 who were entered into the treatment
      registry by one of the 12 participating centers were analyzed. RESULTS: The data
      of 150 infants (292 eyes) were analyzed and ROP 3+ in zone II was the most
      prevalent treatment indication. Gestational age and birth weight remained stable
      over the years. The treatment patterns, however, changed with anti-VEGF treatment
      (bevacizumab or ranibizumab) accounting for only 10% of treated eyes in 2011 but
      for 56% and 30% in 2014 and 2015, respectively. Almost all eyes with AP-ROP or
      zone I disease received anti-VEGF treatment. Zone II disease was predominantly
      treated with laser photocoagulation. Recurrences were more common and appeared
      later in the anti-VEGF group compared to the laser group (23%/interval 60 days
      vs. 17%/interval 23 days). Perioperative complications were evenly distributed
      across treatment groups. CONCLUSION: The data in this analysis represent about 10
      15% of treated infants in Germany. The results provide evidence for an increasing
      use of anti-VEGF agents for ROP. The data reflect a selection bias for anti-VEGF
      treatment in eyes with a more aggressive disease. This needs to be considered
      when interpreting data such as disease recurrence rates. The risk for late
      recurrences after anti-VEGF treatment is of particular clinical significance.

PMID- 29637304
TI  - Intracranial hemorrhage in term neonates.
AB  - BACKGROUND: Intracranial hemorrhage (ICH) is an uncommon but important cause of
      morbidity and mortality in term neonates; currently, ICH is more frequently
      diagnosed because of improved neuroimaging techniques. PURPOSE: The study aims to
      evaluate the clinical characteristics and neuroimaging data (pattern, size,
      distribution) of neonatal ICH. METHODS: We reviewed MRI data from July 2004 to
      June 2015 for 42 term neonates with ICH who were less than 1 month old. We
      recorded clinical data and manifestations, mode of delivery, Apgar score at 1 and
      5 min, associated hypoxic insult, birth trauma, neurological symptoms, EEG
      results, extent and site of hemorrhage, neurosurgical intervention, and
      developmental outcomes. The clinical outcome was determined for 27 neonates. Risk
      factors were assessed in relation to ICH. RESULTS: A total of 42 neonates who
      presented with ICH underwent MR imaging 2 to 22 days postnatally (mean age 9.3
      days). The majority of clinical symptoms were present in patients within the
      first 24 h of life (n = 31), but symptoms appeared until day 10 postnatally (mean
      4.9 days, n = 11). Seizure or seizure-like activity was the most common
      presenting symptom (17/42, 40.5%), with apnea seen in another seven infants
      (7/42, 16.7%). The majority of infants had a normal prenatal course. Two patients
      had antenatally detected hydrocephalus. Ten had infratentorial hemorrhage, and
      two had supratentorial hemorrhage. A total of 30 infants had a combination of
      infratentorial and supratentorial hemorrhage. Subdural hemorrhage (SDH) was the
      most common type of hemorrhage (40/42, 95.2%), followed by nine cases of
      parenchymal hemorrhage, seven of subarachnoid hemorrhage, three of germinal
      matrix hemorrhage (GMH), and one of epidural hemorrhage (EDH). A total of 16
      infants had two or more types of hemorrhage. SDH was identified along the
      tentorium (n = 38) as well as over the cerebellar hemispheres (n = 39), along the
      interhemispheric fissure (n = 10), and over the occipital (n = 13) or
      parietooccipital (n = 11) lobes. Intraparenchymal hemorrhage involved either the
      frontal (n = 4), parietal (n = 3), or cerebellar (n = 2) lobes. Traumatic
      delivery was suspected in 20 patients (47.6%), and perinatal asphyxia was present
      in 21 patients (50.0%). A low Apgar score at 5 min and a history of perinatal
      asphyxia were the factors that most predicted poor clinical outcomes (n = 12/27).
      Logistic regression analysis revealed that a history of perinatal asphyxia
      resulted in poor outcomes. No patients died. One infant required burr hole
      drainage of a right parietal EDH, one infant needed a subcutaneous reservoir, and
      three infants required a ventriculoperitoneal shunt for obstructive
      hydrocephalus. CONCLUSION: SDH was the most common type of ICH in term infants.
      Combined supratentorial and infratentorial hemorrhage was more common than
      isolated infratentorial hemorrhage in these infants. A total of 44.4% of patients
      had poor outcomes, with perinatal asphyxia the most common statistically
      significant cause.

PMID- 29637305
TI  - Peripheral nervous system maturation in preterm infants: longitudinal motor and
      sensory nerve conduction studies.
AB  - OBJECTIVE: To study the evolution of sensory-motor nerves in the upper and lower
      limbs in neurologically healthy preterm infants and to use sensory-motor studies
      to compare the rate of maturation in preterm infants at term age and full-term
      healthy neonates. METHODS: The study comprised 26 neurologically normal preterm
      infants born at 23-33 weeks of gestational age, who underwent sensory nerve
      conduction and motor nerve conduction studies from plantar medial and median
      nerves and from tibial and ulnar nerves, respectively. We repeated the same
      neurophysiological studies in 19 of the preterm infants every 2 weeks until
      postnatal term age. The data from the preterm infants at term was matched with a
      group of ten full-term babies a few days after birth. RESULTS: The motor nerve
      conduction velocity of the tibial and ulnar nerves showed progressive increases
      in values in relation to gestational age, but there was a decrease of values in
      distal latencies and F wave latencies. Similarly, there was a gradual increase of
      sensory nerve conduction velocity values of the medial plantar and median nerves
      and decreases in latencies in relation to gestational age. At term age, the
      preterm infants showed significantly lower values of conduction velocities and
      distal latencies than the full-term neonates. These results were probably because
      the preterm infants had significantly lower weights, total length and, in
      particular, distal segments of the limbs at term age. CONCLUSION: The sensory
      motor conduction parameters were clearly related to gestational age, but
      extrauterine life did not affect the maturation of the peripheral nervous system
      in the very preterm babies who were neurologically healthy.

PMID- 29637306
TI  - Effect of TGFbeta1, TGFbeta3 and keratinocyte conditioned media on functional
      characteristics of dermal fibroblasts derived from reparative (Balb/c) and
      regenerative (Foxn1 deficient; nude) mouse models.
AB  - Skin injuries in mammals are healed through repair or regeneration. Our previous
      studies demonstrated that deficient expression of the transcription factor Foxn1
      in epidermis of nude mice accounts for their skin's pronounced regenerative
      properties. Since homeostasis within the skin depends on complex interactions
      between the epidermal and underlying dermal layers, the present study
      characterizes and compares isolated dermal fibroblasts (DFs) between regenerative
      nude (Foxn1 deficient) mice and their wild-type Balb/c counterparts. Nude DFs
      exhibited a higher cumulative number of population doublings (cumulative PD) at
      low seeding density and increased adipogenic differentiation capacity relative to
      their Balb/c DF counterparts. Nude DFs displayed reduced migration and gel
      contraction, functional features associated with wound healing. The comparison of
      transforming growth factor beta family (TGFbeta) expression showed significantly
      higher levels of Tgfbeta3 transcript between nude and Balb/c mice but no
      differences were detected for Tgfbeta1. Nude DFs were specifically sensitive to
      the presence of the pro-regenerative TGFbeta3 isoform, showing increased collagen
      I deposition and alpha smooth muscle actin expression. Viability of Balb/c DFs
      was stimulated by keratinocyte conditioned media (KCM) from Balb/c (Foxn1 active)
      but inhibited by nude (Foxn1 deficient) KCM. In contrast, nude DFs did not
      respond to either KCMs with respect to their metabolic activity. Collectively,
      the enhanced plasticity and greater sensitivity of nude DFs to TGFbeta3
      stimulation are indicative of and consistent with their pro-regenerative
      characteristics. These data support the hypothesis that epidermal Foxn1 plays a
      critical role in determining the DFs regenerative phenotype.

PMID- 29637307
TI  - The role of HMGB1 in BMSC transplantation for treating MODS in rats.
AB  - The effect of bone marrow mesenchymal stem cells (BMSCs) in treatment for
      multiple organ dysfunction syndrome (MODS) remains unknown and the mechanism is
      still unclear. Therefore, the goal of this study is to investigate the effects of
      intracellular high mobility group box 1 protein (HMGB1) on BMSCs treating for
      MODS. The rats were given 15% blood loss plus 1 mg/kg lipopolysaccharide (LPS)
      via lower extremity superficial venous, then randomly allocated into four groups:
      sham group, MODS group, MODS plus BMSC group, MODS plus ethyl pyruvate (EP)
      group, MODS plus BMSCs plus EP group. Twenty-four hours later, rats in groups
      were sacrificed and then the blood and tissues were collected to evaluate the
      changes of tissue histopathology, cell apoptosis, inflammation level and organ
      function. The HGMB1 expression was monitored by RT-qPCR and Western blot. The
      expression of RAGE/TLR2/TLR4 and NF-kappaB at the protein levels was also
      assessed. BMSCs and/or EP exhibits an outstanding protective effect against LPS
      induced histopathological injury by improving cell apoptosis, inflammatory
      response and the organ dysfunction but no effect on BMSC homing to the injury
      site. Moreover, BMSCs and/or EP inhibited LPS-induced upregulation of HMGB1,
      RAGE, TLR2 and TLR4 expression at protein levels and compromised p65
      phosphorylation in the rat model of MODS. These findings suggest that HMGB1 is
      involved in BMSC treatment for MODS, through regulation of the TLR2, TLR4
      mediated NF-kappaB signal pathway. It suggests that HMGB1 is an attractive
      potential target for the development of new therapeutic strategies for MODS.

PMID- 29637308
TI  - Approaches to cutaneous wound healing: basics and future directions.
AB  - The skin provides essential functions, such as thermoregulation, hydration,
      excretion and synthesis of vitamin D. Major disruptions of the skin cause
      impairment of critical functions, resulting in high morbidity and death, or leave
      one with life-changing cosmetic damage. Due to the complexity of the skin,
      diverse approaches are needed, including both traditional and advanced, to
      improve cutaneous wound healing. Cutaneous wounds undergo four phases of healing.
      Traditional management, including skin grafts and wound dressings, is still
      commonly used in current practice but in combination with newer technology, such
      as using engineered skin substitutes in skin grafts or combining traditional
      cotton gauze with anti-bacterial nanoparticles. Various upcoming methods, such as
      vacuum-assisted wound closure, engineered skin substitutes, stem cell therapy,
      growth factors and cytokine therapy, have emerged in recent years and are being
      used to assist wound healing, or even to replace traditional methods. However,
      many of these methods still lack assessment by large-scale studies and/or
      extensive application. Conceptual changes, for example, precision medicine and
      the rapid advancement of science and technology, such as RNA interference and 3D
      printing, offer tremendous potential. In this review, we focus on the basics of
      wound treatment and summarize recent developments involving both traditional and
      hi-tech therapeutic methods that lead to both rapid healing and better cosmetic
      results. Future studies should explore a more cost-effective, convenient and
      efficient approach to cutaneous wound healing. Graphical abstract Combination of
      various materials to create advanced wound dressings.

PMID- 29637310
TI  - Sulfur-Sulfur Bond Construction.
AB  - Disulfide, as a common structural motif, has been frequently used in
      pharmaceuticals, nature products, and chemical biology. This chapter focuses on
      the methodologies that were reported recently for the synthesis of disulfide
      containing compounds with particular emphasis on the synthesis of unsymmetrical
      disulfides. The presentation is organized according to the structure of the
      disulfides and the synthetic method.

PMID- 29637309
TI  - Advances in Ureteral Stent Design and Materials.
AB  - PURPOSE OF REVIEW: There are three technological parameters that play a key role
      on the performance of an ideal stent. These are its material, design and surface
      coating. This article highlights some fundamental developments that took place in
      these three areas of stent's technology, in order to contribute to the
      identification of an ideal stent. RECENT FINDINGS: In addition to technological
      developments concerning stent's material, design and surface coating, the flow
      dynamic performance of stents has recently attracted increasing attention.
      Notably, it has been postulated that the local flow field in a stent is
      correlated with the deposition of crystals and microorganisms. These findings
      could potentially revolutionise future stent's designs, and complement
      developments made on materials and coatings. The most relevant changes in
      materials, designs and surface coatings of ureteric stents are reviewed in this
      article. These are described in the context of a specific cause of stent's
      failure they aim to address, with a particular focus on encrustation and biofilm
      formation.

PMID- 29637311
TI  - Institutional Pathways to Improve Care of Patients with Elevated Blood Pressure
      in the Emergency Department.
AB  - PURPOSE OF REVIEW: Hypertension (HTN) is the most prevalent cardiovascular
      disease and poses a major population level risk to long-term health outcomes.
      Despite this critical importance, and the widespread availability of effective
      and affordable medications, blood pressure (BP) remains uncontrolled in up to 50%
      of the diagnosed patients. This problem is exacerbated in communities with
      limited access to primary care, who often utilize hospital emergency departments
      (EDs) as their primary healthcare resource. Despite the ubiquity of patients
      presenting to EDs with severely elevated BP, a unified, evidence-based approach
      is not yet widely implemented, and both under- and overtreatment are common. The
      purpose of this review is to describe an approach towards institutional policy
      regarding asymptomatic HTN, in which we will translate the accepted principles of
      appropriate outpatient BP management to ED and inpatient settings. RECENT
      FINDINGS: Results from the recent SPRINT trial, and the subsequent publication of
      the American Heart Association updated guidelines for the treatment of HTN,
      significantly lower both the diagnostic threshold and the treatment goals for
      hypertensive patients. This change will drastically increase the proportion of
      patients presenting to EDs with newly diagnosed and uncontrolled HTN. Several
      recent studies emphasize the safety in outpatient management of patients with
      severely elevated BP in the absence of acute end-organ damage and, conversely,
      the long- and intermediate-term risk associated with these patients. System-based
      approaches, particularly those led by non-physicians, have shown the greatest
      promise in reducing population level uncontrolled HTN. Evidence-based approaches,
      such as those described in emergency medicine and cardiology society guidelines,
      can guide appropriate management of ED and inpatient BP elevations. Translating
      these patient oriented guidelines into institutional policy, and maintaining
      provider adherence, is a challenge across healthcare institutions. We present
      here several examples of successful policies developed and implemented by the
      authors. While brief inpatient and ED encounters cannot replace long-term
      outpatient care, they have the potential to serve as a crucial inlet to health
      care and an opportunity to optimize care.

PMID- 29637312
TI  - Updates to Adherence to Hypertension Medications.
AB  - PURPOSE OF REVIEW: The purpose of this review is to discuss recent studies that
      have described approaches or interventions to improve hypertension medication
      adherence and to suggest how providers can integrate evidenced-based approaches
      into routine clinical care to improve medication adherence and blood pressure
      control. RECENT FINDINGS: Factors that can impact medication include patient
      related factors, social- and economic-related factors, health system/health care
      team-related factors, and therapy-related factors. Overall, a multifaceted
      approach is needed to improve medication adherence. Important components include
      (1) patient education on hypertension, its treatment modalities and its long-term
      complications; and (2) patient engagement building on the foundation of
      education. The various interventions tested have engaged patients through
      interactive educational sessions, health coaching, motivational interviewing,
      stage of change behavioral counseling, and pharmacist hypertension management.
      Strategies utilizing patient education and engagement are needed to improve
      medication adherence and blood pressure control.

PMID- 29637313
TI  - Paternal perception of infant sleep risks and safety.
AB  - BACKGROUND: Sudden Unexpected Infant Death (SUID) results in 3400 sleep-related
      deaths yearly in the United States, yet caregivers' compliance with safe sleep
      recommendations remains less than optimal. Paternal caregiver's attitudes toward
      infant safe sleep messages are largely unaddressed, despite established
      differences between female and male caregiver perceptions. This study aimed to
      explore the determinants of safe sleep practices among male caregivers. METHODS:
      Focus groups were conducted in Arkansas with male caregivers of infants ages 2-12
      months to discuss infant sleep routines, parental roles, sources for safe sleep
      information, and messaging suggestions for safe sleep promotion. The Health
      Belief Model of behavior change framed a moderator guide. Transcript-based
      analysis was used, and data were managed using HyperRESEARCH (version 2.8.3). The
      transcribed data were coded to identify significant themes. RESULTS: Ten focus
      groups were conducted with 46 participants. Inconsistent adherence to safe sleep
      practices was reported. Participants were more likely to describe safe location
      (57% of participants) and supine position behaviors (42%) than an uncluttered bed
      environment (26%). Caregivers acknowledged the importance of recommended safe
      sleep behavior, but admitted to unsafe practices, such as co-sleeping and unsafe
      daytime sleep. Lack of perceived risk, comfort, and/or resources, and
      disagreement among family members about safety practices were identified as
      barriers. Participants voiced concerns that current advertising portrays males as
      incompetent caregivers. Suggestions included portraying positive images of
      fathers and male caregivers acting to promote safety and the incorporation of
      statistics about the hazards of unsafe sleep to better engage fathers. Potential
      distribution venues included sporting events, home improvement and/or automotive
      stores, and social media from trusted sites (e.g. hospitals or medical
      professionals). CONCLUSIONS: Male caregivers demonstrate some knowledge base
      about infant sleep safety, but are not fully practicing all aspects of safe
      sleep. Targeted messaging towards male caregivers that includes factual
      information and statistics along with representing males in a positive light is
      desired.

PMID- 29637314
TI  - Community Outreach to African-Americans: Implementations for Controlling
      Hypertension.
AB  - PURPOSE OF REVIEW: The purpose of this review is to examine the impact and
      effectiveness of community interventions for controlling hypertension in African
      Americans. The questions addressed are as follows: Which salient prior and
      current community efforts focus on African-Americans and are most effective in
      controlling hypertension and patient-related outcomes? How are these efforts
      implemented and possibly sustained? RECENT FINDINGS: The integration of out-of
      office blood pressure measurements, novel hypertension control centers (i.e.,
      barbershops), and community health workers improve hypertension control and may
      reduce the excess hypertension-related complications in African-Americans.
      Several community-based interventions may assist effectiveness of clinical care
      teams, decrease care barriers, and improve adherence. A multifaceted, tailored,
      multidisciplinary community-based approach may effectively reduce barriers to
      blood pressure control among African-Americans. Future research should evaluate
      the long-term benefits of community health workers, barbershops as control
      centers, and out-of-office blood pressure monitoring upon control and eventually
      on morbidity and mortality.

PMID- 29637315
TI  - Impact of cognitive function on oral perception in independently living older
      people.
AB  - OBJECTIVES: Oral tactile perception is important for better mastication,
      appetite, and enjoyment of food. However, previous investigations have not
      utilized comprehensible variables thought to have negative effect on oral
      perception, including aging, denture wearing, and cognitive function. The aim of
      this study was to elucidate the impact of cognitive function on oral perception
      in independently living older individuals. MATERIALS AND METHODS: The study
      sample was comprised of 987 participants (466 males, 521 females; age 69-71
      years). Oral examinations, assessments of cognitive function in preclinical level
      by Montreal Cognitive Assessment (MoCA)-J, and determination of oral
      stereognostic ability as an indicator of oral perception were performed. Related
      variables were selected by univariate analyses; then, multivariate logistic
      regression model analysis was conducted. RESULTS: Univariate analyses revealed
      that number of teeth, removable dentures usage, and cognitive function
      respectively had a significant relationship with stereognostic score. Next, the
      subjects were classified into good and poor perception groups (lowest 17.4%)
      according to oral stereognostic ability. Logistic regression analysis revealed
      that lower cognitive function was significantly associated with poor oral
      perception (OR = 0.934, p = 0.017) after controlling for other variables.
      CONCLUSIONS: Cognitive decline even in preclinical stage was associated with
      reduced oral perception after controlling for gender, tooth number and denture
      use in independent living older people. CLINICAL RELEVANCE: This study suggested
      that preclinical level of change in cognitive function affected oral perception.
      Dental practitioners and caregivers may need to pay attention to reduced oral
      perception among older people even if they do not have trouble in daily life.

PMID- 29637316
TI  - Experimental Verification of the Elastic Formula for the Aspirated Length of a
      Single Cell Considering the Size and Compressibility of Cell During Micropipette
      Aspiration.
AB  - In this study, an aspiration system for elastic spheres was developed to verify
      the approximate elastic formula for the aspirated length of a single solid-like
      cell undergoing micropipette aspiration (MPA), which was obtained in our previous
      study by theoretical analysis and numerical simulation. Using this system, foam
      silicone rubber spheres with different diameters and mechanical properties were
      aspirated in a manner similar to the MPA of single cells. Comparisons between the
      approximate elastic formula and aspiration experiments of spheres indicated that
      the predictions of the formula agreed with the experimental results.
      Additionally, combined with the MPA data of rabbit chondrocytes, differences in
      terms of the elastic parameters derived from the half-space model, incompressible
      sphere model, and compressible sphere model were explored. The results
      demonstrated that the parameter xi (xi = R/a, where R is the radius of the cell
      and a is the inner radius of the micropipette) and Poisson's ratio significantly
      influenced the determination of the elastic modulus and bulk modulus of the cell.
      This work developed for the first time an aspiration system of elastic spheres to
      study the elastic responses of the MPA of a single cell and provided new evidence
      supporting the use of the approximate elastic formula to determine cellular
      elastic parameters from the MPA data.

PMID- 29637317
TI  - Round-shape gold nanoparticles: effect of particle size and concentration on
      Arabidopsis thaliana root growth.
AB  - Nowadays, due to a wide range of applications of nanoparticles (NPs) in many
      industrial areas, accumulations of those entities in environment pose a great
      risk. Owing to their inertness, noble metal NPs may remain in contaminated soils
      nearly unchanged for long time. Within this context, size-, shape-, and
      concentration-dependent uptake of particles by plants belongs to unexplored area.
      In this work, we present water solutions of biologically friendly synthesized
      spherical AuNPs with pretty narrow size distribution in size range from 10 to 18
      nm. Their thorough characterization by atomic absorption spectroscopy, mass
      spectroscopy-equipped inductively coupled plasma, dynamic light scattering (DLS),
      and TEM methods was followed by the study of their effect on the growth of
      Arabidopsis thaliana (primary and lateral roots), in particle size- and
      concentration-dependent manner. Due to strictly round-shape form of AuNPs and
      absence of particle agglomeration, DLS-derived size and size distribution were in
      good concordance with those obtained from TEM. The length and number of A.
      thaliana lateral roots were significantly affected by all types of AuNPs.
      Smallest AuNPs at highest concentration inhibited length of primary roots and, in
      contrast, enhanced hair root growth.

PMID- 29637318
TI  - Bringing Darwin into the social sciences and the humanities: cultural evolution
      and its philosophical implications.
AB  - In the field of cultural evolution it is generally assumed that the study of
      culture and cultural change would benefit enormously from being informed by
      evolutionary thinking. Recently, however, there has been much debate about what
      this "being informed" means. According to the standard view, an interesting
      analogy obtains between cultural and biological evolution. In the literature,
      however, the analogy is interpreted and used in at least three distinct, but
      interrelated ways. We provide a taxonomy in order to clarify these different
      meanings. Subsequently, we discuss the alternatives model of cultural attraction
      theory and memetics, which both challenge basic assumptions of the standard view.
      Finally, we briefly summarize the contributions to the special issue on Darwin in
      the Humanities and the Social Sciences, which is the result of a collaborative
      project between scholars and scientists from the universities of Lille and Ghent.
      Furthermore, we explain how they add to the discussions about the integration of
      evolutionary thinking and the study of culture.

PMID- 29637319
TI  - The Psychological Effects of Climate Change on Children.
AB  - PURPOSE OF REVIEW: We review recent evidence on the psychological effects of
      climate change on children, covering both direct and indirect impacts, and
      discuss children's psychological adaptation to climate change. RECENT FINDINGS:
      Both the direct and flow-on effects of climate change place children at risk of
      mental health consequences including PTSD, depression, anxiety, phobias, sleep
      disorders, attachment disorders, and substance abuse. These in turn can lead to
      problems with emotion regulation, cognition, learning, behavior, language
      development, and academic performance. Together, these create predispositions to
      adverse adult mental health outcomes. Children also exhibit high levels of
      concern over climate change. Meaning-focused coping promotes well-being and
      environmental engagement. Both direct and indirect climate change impacts affect
      children's psychological well-being. Children in the developing world will suffer
      the worst impacts. Mental health professionals have important roles in helping
      mitigate climate change, and researching and implementing approaches to helping
      children cope with its impacts.

PMID- 29637321
TI  - Twenty-two years of injury free.

PMID- 29637322
TI  - The Abecedarian Approach to Social, Educational, and Health Disparities.
AB  - This paper places the Abecedarian Approach in theoretical and historical context
      and reviews the results from three randomized controlled trials that have tested
      an experimental protocol designed to prevent cognitive disabilities and their
      social consequences. Results affirm that cognitive disabilities can be prevented
      in early childhood and subsequent academic achievement enhanced via a
      multipronged comprehensive approach that contains individualized and responsive
      early childhood education starting in early infancy, coupled with pediatric
      health care, good nutrition, and family-oriented social services. Additional
      important findings reveal that the most vulnerable children benefited the most
      and that cognitive gains were not at the expense of children's socioemotional
      development or relationship to family. In general, mothers derived benefits in
      education and employment and teenage mothers especially benefited from their
      children participating in the early education treatment group. On the whole, the
      overall pattern of results supports a multidisciplinary, individualized, and long
      term longitudinal perspective on human development and prevention science. Recent
      structural and functional brain imaging in the fifth decade of life shows
      persistent effects of intensive early educational treatment. Independent recent
      cost-benefit analysis in adulthood reveals a 7.3:1 return on investment with a
      13.7% average annual rate of return. The paper concludes with a discussion of
      implications of the Abecedarian Approach to today's high-risk population in the
      USA.

PMID- 29637320
TI  - Monitoring spatial and temporal variation of dissolved oxygen and water
      temperature in the Savannah River using a sensor network.
AB  - Dissolved oxygen is a critical component of river water quality. This study
      investigated average weekly dissolved oxygen (AWDO) and average weekly water
      temperature (AWT) in the Savannah River during 2015 and 2016 using data from the
      Intelligent River(r) sensor network. Weekly data and seasonal summary statistics
      revealed distinct seasonal patterns that impact both AWDO and AWT regardless of
      location along the river. Within seasons, spatial patterns of AWDO and AWT along
      the river are also evident. Linear mixed effects models indicate that AWT and low
      and high river flow conditions had a significant impact on AWDO, but added little
      predictive information to the models. Low and high river flow conditions had a
      significant impact on AWT, but also added little predictive information to the
      models. Spatial linear mixed effects models yielded parameter estimates that were
      effectively the same as non-spatial linear mixed effects models. However,
      components of variance from spatial linear mixed effects models indicate that 23
      32% of the total variance in AWDO and that 12-18% of total variance in AWT can be
      apportioned to the effect of spatial covariance. These results indicate that
      location, week, and flow-directional spatial relationships are critically
      important considerations for investigating relationships between space- and time
      varying water quality metrics.

PMID- 29637323
TI  - Cross-cultural adaptation and psychometric evaluation of the Juvenile Arthritis
      Multidimensional Assessment Report (JAMAR) in 54 languages across 52 countries:
      review of the general methodology.
AB  - The aim of this project was to cross-culturally adapt and validate the Juvenile
      Arthritis Multidimensional Assessment Report (JAMAR) questionnaire in 54
      languages across 52 different countries that are members of the Paediatric
      Rheumatology International Trials Organisation (PRINTO). This effort was part of
      a wider project named Epidemiology and Outcome of Children with Arthritis (EPOCA)
      to obtain information on the frequency of juvenile idiopathic arthritis (JIA)
      categories in different geographic areas, the therapeutic approaches adopted, and
      the disease status of children with JIA currently followed worldwide. A total of
      13,843 subjects were enrolled from the 49 countries that took part both in the
      cross-cultural adaptation phase and in the related validation and data
      collection: Algeria, Argentina, Belgium, Brazil, Bulgaria, Canada, Chile,
      Colombia, Croatia, Czech Republic, Denmark, Ecuador, Egypt, Estonia, Finland,
      France, Georgia, Germany, Greece, Hungary, India, Islamic Republic of Iran,
      Israel, Italy, Latvia, Libya, Lithuania, Mexico, Netherlands, Norway, Oman,
      Paraguay, Poland, Portugal, Romania, Russian Federation, Saudi Arabia, Serbia,
      Slovakia, Slovenia, South Africa, Spain, Sweden, Switzerland, Thailand, Turkey,
      Ukraine, United Kingdom and United States of America. 9021 patients had JIA
      (10.7% systemic arthritis, 41.9% oligoarthritis, 23.5% RF negative polyarthritis,
      4.2% RF positive polyarthritis, 3.4% psoriatic arthritis, 10.6% enthesitis
      related arthritis and 5.7% undifferentiated arthritis) while 4822 were healthy
      children. This introductory paper describes the overall methodology; results
      pertaining to each country are fully described in the accompanying manuscripts.
      In conclusion, the JAMAR translations were found to have satisfactory
      psychometric properties and it is thus a reliable and valid tool for the
      multidimensional assessment of children with JIA.

PMID- 29637324
TI  - The Italian version of the Juvenile Arthritis Multidimensional Assessment Report
      (JAMAR).
AB  - The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new
      parent/patient reported outcome measure that enables a thorough assessment of the
      disease status in children with juvenile idiopathic arthritis (JIA). We report
      the results of the cross-cultural adaptation and validation of the parent and
      patient versions of the JAMAR in the Italian language.The reading comprehension
      of the questionnaire was tested in 10 JIA parents and patients. Each
      participating centre was asked to collect demographic, clinical data and the
      JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6
      month period and to administer the JAMAR to 100 healthy children and their
      parents.The statistical validation phase explored descriptive statistics and the
      psychometric issues of the JAMAR: the 3 Likert assumptions, floor/ceiling
      effects, internal consistency, Cronbach's alpha, interscale correlations, test
      retest reliability, and construct validity (convergent and discriminant
      validity).A total of 1296 JIA patients (7.2% systemic, 59.5% oligoarticular,
      21.4% RF negative polyarthritis, 11.9% other categories) and 100 healthy
      children, were enrolled in 18 centres. The JAMAR components discriminated well
      healthy subjects from JIA patients except for the Health Related Quality of Life
      (HRQoL) Psychosocial Health (PsH) subscales. All JAMAR components revealed good
      psychometric performances.In conclusion, the Italian version of the JAMAR is a
      valid tool for the assessment of children with JIA and is suitable for use both
      in routine clinical practice and clinical research.

PMID- 29637325
TI  - The German version of the Juvenile Arthritis Multidimensional Assessment Report
      (JAMAR).
AB  - The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new
      parent/patient reported outcome measure that enables a thorough assessment of the
      disease status in children with juvenile idiopathic arthritis (JIA). We report
      the results of the cross-cultural adaptation and validation of the parent and
      patient versions of the JAMAR in the German language. The reading comprehension
      of the questionnaire was tested in 10 JIA parents and patients. The participating
      centres were asked to collect demographic and clinical data along the JAMAR
      questionnaire in 100 consecutive JIA patients or all consecutive patients seen in
      a 6-month period and to administer the JAMAR to 100 healthy children and their
      parents. The statistical validation phase explored descriptive statistics and the
      psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling
      effects, internal consistency, Cronbach's alpha, interscale correlations, test
      retest reliability, and construct validity (convergent and discriminant
      validity). A total of 319 JIA patients (2.8% systemic, 36.7% oligoarticular,
      23.5% RF negative polyarthritis, and 37% other categories) and 100 healthy
      children were enrolled in eight centres. The JAMAR components discriminated well
      healthy subjects from JIA patients. All JAMAR components revealed good
      psychometric performances. In conclusion, the German version of the JAMAR is a
      valid tool for the assessment of children with JIA and is suitable for use both
      in routine clinical practice and in clinical research.

PMID- 29637326
TI  - The Greek version of the Juvenile Arthritis Multidimensional Assessment Report
      (JAMAR).
AB  - The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new
      parent/patient-reported outcome measure that enables a thorough assessment of the
      disease status in children with juvenile idiopathic arthritis (JIA). We report
      the results of the cross-cultural adaptation and validation of the parent and
      patient versions of the JAMAR in the Greek language. The reading comprehension of
      the questionnaire was tested in 10 JIA parents and patients. Each participating
      centre was asked to collect demographics, clinical data, and the JAMAR from 100
      consecutive JIA patients or all consecutive patients seen in a 6-month period and
      to administer the JAMAR to 100 healthy children and their parents. The
      statistical validation phase explored descriptive statistics and the psychometric
      issues of the JAMAR: the three Likert assumptions, floor/ceiling effects,
      internal consistency, Cronbach's alpha, interscale correlations, test-retest
      reliability, and construct validity (convergent and discriminant validity). The
      Greek JAMAR was fully cross-culturally adapted with two forward and three
      backward translations. A total of 272 JIA patients (5.9% systemic, 57.7%
      oligoarticular, 21.3% RF negative poly-arthritis, 15.1% other categories), and
      100 healthy children were enrolled in all centres. The JAMAR components
      discriminated well-healthy subjects from JIA patients; notably, there was no
      significant difference between healthy subjects and their affected peers in
      psychosocial quality of life and school-related items. All JAMAR components
      revealed good psychometric performances. In conclusion, the Greek version of the
      JAMAR is a valid tool for the assessment of children with JIA and is suitable for
      use both in routine clinical practice and in clinical research.

PMID- 29637327
TI  - The Norwegian version of the Juvenile Arthritis Multidimensional Assessment
      Report (JAMAR).
AB  - The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new
      parent/patient-reported outcome measure that enables a thorough assessment of the
      disease status in children with juvenile idiopathic arthritis (JIA). We report
      the results of the cross-cultural adaptation and validation of the parent and
      patient versions of the JAMAR in the Norwegian language. The reading
      comprehension of the questionnaire was tested in 10 JIA parents and patients.
      Each participating centre was asked to collect demographic and clinical data and
      the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6
      month period and to administer the JAMAR to 100 healthy children and their
      parents. The statistical validation phase explored descriptive statistics and the
      psychometric issues of the JAMAR: the 3 Likert assumptions, floor/ceiling
      effects, internal consistency, Cronbach's alpha, interscale correlations, test
      retest reliability, and construct validity (convergent and discriminant
      validity). A total of 301 JIA patients (3.3% systemic, 41.2% oligoarticular,
      25.9% RF negative polyarthritis, and 29.6% other categories) and 74 healthy
      children were enrolled in three centres. The JAMAR components discriminated well
      healthy subjects from JIA patients. All JAMAR components revealed good
      psychometric performances. In conclusion, the Norwegian version of the JAMAR is a
      valid tool for the assessment of children with JIA and is suitable for use both
      in routine clinical practice and clinical research.

PMID- 29637328
TI  - The Castilian Spanish version of the Juvenile Arthritis Multidimensional
      Assessment Report (JAMAR).
AB  - The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new
      parent/patient reported outcome measure that enables a thorough assessment of the
      disease status in children with juvenile idiopathic arthritis (JIA). We report
      the results of the cross-cultural adaptation and validation of the parent and
      patient versions of the JAMAR in the Castilian Spanish language. The reading
      comprehension of the questionnaire was tested in 10 JIA parents and patients.
      Each participating centre was asked to collect demographic, clinical data and the
      JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6
      month period and to administer the JAMAR to 100 healthy children and their
      parents. The statistical validation phase explored descriptive statistics and the
      psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling
      effects, internal consistency, Cronbach's alpha, interscale correlations, test
      retest reliability and construct validity (convergent and discriminant validity).
      A total of 526 JIA patients (8.6% systemic, 49.4% oligoarticular, 18.2% RF
      negative polyarthritis, 23.8% other categories) and 78 healthy children, were
      enrolled in six centres. The JAMAR components discriminated well healthy subjects
      from JIA patients. All JAMAR components revealed good psychometric performances.
      In conclusion, the Castilian Spanish version of the JAMAR is a valid tool for the
      assessment of children with JIA and is suitable for use both in routine clinical
      practise and clinical research.

PMID- 29637329
TI  - The Turkish version of the Juvenile Arthritis Multidimensional Assessment Report
      (JAMAR).
AB  - The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new
      parent/patient reported outcome measure that enables a thorough assessment of the
      disease status in children with juvenile idiopathic arthritis (JIA). We report
      the results of the cross-cultural adaptation and validation of the parent and
      patient versions of the JAMAR in the Turkish language. The reading comprehension
      of the questionnaire was tested in 10 JIA parents and patients. Each
      participating centre was asked to collect demographic, clinical data and the
      JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6
      month period and to administer the JAMAR to 100 healthy children and their
      parents. The statistical validation phase explored descriptive statistics and the
      psychometric issues of the JAMAR: the 3 Likert assumptions, floor/ceiling
      effects, internal consistency, Cronbach's alpha, interscale correlations, test
      retest reliability, and construct validity (convergent and discriminant
      validity). A total of 466 JIA patients (13.7% systemic, 40.6% oligoarticular,
      22.5% RF negative poly-arthritis, and 23.2% other categories) and 93 healthy
      children were enrolled in four centres. The JAMAR components discriminated well
      healthy subjects from JIA patients. All JAMAR components revealed good
      psychometric performances. In conclusion, the Turkish version of the JAMAR is a
      valid tool for the assessment of children with JIA and is suitable for use both
      in routine clinical practice and clinical research.

PMID- 29637330
TI  - The Hindi version of the Juvenile Arthritis Multidimensional Assessment Report
      (JAMAR).
AB  - The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new
      parent/patient-reported outcome measure that enables a thorough assessment of the
      disease status in children with juvenile idiopathic arthritis (JIA). We report
      the results of the cross-cultural adaptation and validation of the parent and
      patient versions of the JAMAR in the Hindi language. The reading comprehension of
      the questionnaire was tested in ten JIA parents and patients. Each participating
      centre was asked to collect demographic, clinical data and the JAMAR in 100
      consecutive JIA patients or all consecutive patients seen in a 6-month period and
      to administer the JAMAR to 100 healthy children and their parents. The
      statistical validation phase explored descriptive statistics and the psychometric
      issues of the JAMAR: the three Likert assumptions, floor/ceiling effects,
      internal consistency, Cronbach's alpha, interscale correlations, test-retest
      reliability, and construct validity (convergent and discriminant validity). A
      total of 275 JIA patients (28.4% systemic, 10.9% oligoarticular, 13.8% RF
      negative polyarthritis, 46.9% other categories) and 98 healthy children were
      enrolled in three centres. The JAMAR components discriminated well healthy
      subjects from JIA patients. Notably, there is no significant difference between
      the healthy subjects and their affected peers in the school-related problems
      variable. All JAMAR components revealed good psychometric performances. In
      conclusion, the Hindi version of the JAMAR is a valid tool for the assessment of
      children with JIA and is suitable for use both in routine clinical practice and
      clinical research.

PMID- 29637331
TI  - The Croatian version of the Juvenile Arthritis Multidimensional Assessment Report
      (JAMAR).
AB  - The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new
      parent/patient reported outcome measure that enables a thorough assessment of the
      disease status in children with juvenile idiopathic arthritis (JIA). We report
      the results of the cross-cultural adaptation and validation of the parent and
      patient versions of the JAMAR in the Croatian language. The reading comprehension
      of the questionnaire was tested in 10 JIA parents and patients. Each
      participating centre was asked to collect demographic, clinical data and the
      JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6
      month period and to administer the JAMAR to 100 healthy children and their
      parents. The statistical validation phase explored descriptive statistics and the
      psychometric issues of the JAMAR: the 3 Likert assumptions, floor/ceiling
      effects, internal consistency, Cronbach's alpha, interscale correlations, test
      retest reliability and construct validity (convergent and discriminant validity).
      A total of 100 JIA patients (7% systemic, 38% oligoarticular, 19% RF negative
      polyarthritis, 36% other categories) and 100 healthy children, were enrolled in
      the paediatric rheumatology centres of the Clinical Hospital Center Sestre
      Milosrdnice and Childen's Hospital Srebrnjak in Zagreb. The JAMAR components
      discriminated well healthy subjects from JIA patients. All JAMAR components
      revealed satisfactory psychometric performances. In conclusion, the Croatian
      version of the JAMAR is a valid tool for the assessment of children with JIA and
      is suitable for use both in routine clinical practice and clinical research.

PMID- 29637332
TI  - The Finnish version of the Juvenile Arthritis Multidimensional Assessment Report
      (JAMAR).
AB  - The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new
      parent/patient-reported outcome measure that enables a thorough assessment of the
      disease status in children with juvenile idiopathic arthritis (JIA). We report
      the results of the cross-cultural adaptation and validation of the parent and
      patient versions of the JAMAR in the Finnish language. The reading comprehension
      of the questionnaire was tested in ten JIA parents and patients. Each
      participating centre was asked to collect demographic, clinical data and the
      JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6
      month period and to administer the JAMAR to 100 healthy children and their
      parents. The statistical validation phase explored descriptive statistics and the
      psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling
      effects, internal consistency, Cronbach's alpha, interscale correlations, test
      retest reliability, and construct validity (convergent and discriminant
      validity). A total of 173 JIA patients (1.2% systemic, 46.2% oligoarticular,
      39.9% RF-negative polyarthritis, 12.7% other categories) and 100 healthy
      children, were enrolled in five paediatric rheumatology centres. The JAMAR
      components discriminated well healthy subjects from JIA patients. All JAMAR
      components revealed good psychometric performances. In conclusion, the Finnish
      version of the JAMAR is a valid tool for the assessment of children with JIA and
      is suitable for use both in routine clinical practice and clinical research.

PMID- 29637333
TI  - The Romanian version of the Juvenile Arthritis Multidimensional Assessment Report
      (JAMAR).
AB  - The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new
      parent/patient-reported outcome measure that enables a thorough assessment of the
      disease status in children with juvenile idiopathic arthritis (JIA). We report
      the results of the cross-cultural adaptation and validation of the parent and
      patient versions of the JAMAR in the Romanian language. The reading comprehension
      of the questionnaire was tested in 15 JIA parents and patients. Each
      participating centre was asked to collect demographic, clinical data and the
      JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6
      month period and to administer the JAMAR to 100 healthy children and their
      parents. The statistical validation phase explored descriptive statistics and the
      psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling
      effects, internal consistency, Cronbach's alpha, interscale correlations, test
      retest reliability, and construct validity (convergent and discriminant
      validity). A total of 310 JIA patients (11.9% systemic, 21.6% oligoarticular,
      31.9% RF-negative polyarthritis, 34.6% other categories) and 100 healthy
      children, were enrolled in six centres. The JAMAR components discriminated well
      healthy subjects from JIA patients except for the health-related quality of life
      psychosocial health subscales. All JAMAR components revealed good psychometric
      performances. In conclusion, the Romanian version of the JAMAR is a valid tool
      for the assessment of children with JIA and is suitable for use both in routine
      clinical practice and clinical research.

PMID- 29637334
TI  - The Argentinian Spanish version of the Juvenile Arthritis Multidimensional
      Assessment Report (JAMAR).
AB  - The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new
      parent/patient reported outcome measure that enables a thorough assessment of the
      disease status in children with juvenile idiopathic arthritis (JIA). We report
      the results of the cross-cultural adaptation and validation of the parent and
      patient versions of the JAMAR in the Argentinian Spanish language. The reading
      comprehension of the questionnaire was tested in 10 JIA parents and patients.
      Each participating centre was asked to collect demographic, clinical data and the
      JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6
      month period and to administer the JAMAR to 100 healthy children and their
      parents. The statistical validation phase explored descriptive statistics and the
      psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling
      effects, internal consistency, Cronbach's alpha, interscale correlations, test
      retest reliability, and construct validity (convergent and discriminant
      validity). A total of 373 JIA patients (23.1% systemic, 30.8% oligoarticular,
      28.1% RF negative polyarthritis, 18% other categories) and 100 healthy children
      were enrolled in five centres. The JAMAR components discriminated well healthy
      subjects from JIA patients. Notably, there was no significant difference between
      healthy subjects and their affected peers in the school-related item. All JAMAR
      components revealed good psychometric performances. In conclusion, the
      Argentinian Spanish version of the JAMAR is a valid tool for the assessment of
      children with JIA and is suitable for use both in routine clinical practice and
      clinical research.

PMID- 29637335
TI  - The Libyan Arabic version of the Juvenile Arthritis Multidimensional Assessment
      Report (JAMAR).
AB  - The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new
      parent/patient reported outcome measure that enables a thorough assessment of the
      disease status in children with juvenile idiopathic arthritis (JIA). We report
      the results of the cross-cultural adaptation and validation of the parent and
      patient versions of the JAMAR in the Libyan Arabic language. The reading
      comprehension of the questionnaire was tested in 10 JIA parents and patients.
      Each participating centre was asked to collect demographic, clinical data, and
      the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6
      month period and to administer the JAMAR to 100 healthy children and their
      parents. The statistical validation phase explored descriptive statistics and the
      psychometric issues of the JAMAR: the 3 Likert assumptions, floor/ceiling
      effects, internal consistency, Cronbach's alpha, interscale correlations, test
      retest reliability, and construct validity (convergent and discriminant
      validity). A total of 100 JIA patients (22.0% systemic, 26.0% oligoarticular,
      25.0% RF negative polyarthritis, and 27.0% other categories) and 100 healthy
      children, were enrolled in a paediatric rheumatology centre. The JAMAR components
      discriminated well healthy subjects from JIA patients. Notably, there is no
      significant difference between the healthy subjects and their affected peers in
      the school-related problems variable. All JAMAR components revealed satisfactory
      psychometric performances. In conclusion, the Libyan Arabic version of the JAMAR
      is a valid tool for the assessment of children with JIA and is suitable for use
      both in routine clinical practice and clinical research.

PMID- 29637336
TI  - The Canadian English and French versions of the Juvenile Arthritis
      Multidimensional Assessment Report (JAMAR).
AB  - The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new
      parent/patient reported outcome measure that enables a thorough assessment of the
      disease status in children with juvenile idiopathic arthritis (JIA). We report
      the results of the cross-cultural adaptation and validation of the parent and
      patient versions of the JAMAR in the Canadian varieties of English and French.
      The reading comprehension of the questionnaires were tested in a probe sample of
      ten parents and ten JIA patients for Canadian English and other ten parents and
      ten JIA patients for Canadian French. Each participating centre was asked to
      collect demographic, clinical data and the JAMAR in 100 consecutive JIA patients
      or all consecutive patients seen in a 6-month period and to administer the JAMAR
      to 100 healthy children and their parents. The statistical validation phase
      explored descriptive statistics and the psychometric issues of the JAMAR: the 3
      Likert assumptions, floor/ceiling effects, internal consistency, Cronbach's
      alpha, interscale correlations, test-retest reliability and construct validity
      (convergent and discriminant validity). A total of 208 JIA patients (2.9%
      systemic, 41.8% oligoarticular, 27.9% RF negative polyarthritis, 27.4% other
      categories) and 152 healthy children, were enrolled at two paediatric
      rheumatology centres. The JAMAR components discriminated well healthy subjects
      from JIA patients. Notably, there was no significant difference between the
      healthy subjects and their affected peers in the psychosocial quality of life
      variable. All JAMAR components revealed good psychometric performances. In
      conclusion, the Canadian English and French versions of the JAMAR are valid tools
      for the assessment of children with JIA and are suitable for use both in routine
      clinical practice and clinical research.

PMID- 29637337
TI  - The Bulgarian version of the Juvenile Arthritis Multidimensional Assessment
      Report (JAMAR).
AB  - The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new
      parent/patient reported outcome measure that enables a thorough assessment of the
      disease status in children with juvenile idiopathic arthritis (JIA). We report
      the results of the cross-cultural adaptation and validation of the parent and
      patient versions of the JAMAR in the Bulgarian language. The reading
      comprehension of the questionnaire was tested in 10 JIA parents and patients.
      Each participating centre was asked to collect demographic, clinical data, and
      the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6
      month period and to administer the JAMAR to 100 healthy children and their
      parents. The statistical validation phase explored descriptive statistics and the
      psychometric issues of the JAMAR: the 3 Likert assumptions, floor/ceiling
      effects, internal consistency, Cronbach's alpha, interscale correlations, test
      retest reliability, and construct validity (convergent and discriminant
      validity). A total of 183 JIA patients (12% systemic, 53.6% oligoarticular, 23.5%
      RF negative polyarthritis, 10.9% other categories) and 100 healthy children were
      enrolled in two centres. The JAMAR components discriminated well healthy subjects
      from JIA patients. Notably, there is no significant difference between the
      healthy subjects and their affected peers in the school-related problems
      variable. All JAMAR components revealed good psychometric performances. In
      conclusion, the Bulgarian version of the JAMAR is a valid tool for the assessment
      of children with JIA and is suitable for use both in routine clinical practice
      and clinical research.

PMID- 29637338
TI  - The American English version of the Juvenile Arthritis Multidimensional
      Assessment Report (JAMAR).
AB  - The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new
      parent/patient-reported outcome measure that enables a thorough assessment of the
      disease status in children with juvenile idiopathic arthritis (JIA). We report
      the results of the cross-cultural adaptation and validation of the parent and
      patient versions of the JAMAR in the American English language. The reading
      comprehension of the questionnaire was tested in 10 JIA parents and patients.
      Each participating centre was asked to collect demographic, clinical data and the
      JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6
      month period and to administer the JAMAR to 100 healthy children and their
      parents. The statistical validation phase explored descriptive statistics and the
      psychometric issues of the JAMAR: the 3 Likert assumptions, floor/ceiling
      effects, internal consistency, Cronbach's alpha, interscale correlations, test
      retest reliability, and construct validity (convergent and discriminant
      validity). A total of 315 JIA patients (5.1% systemic, 31.1% oligoarticular, 34%
      RF negative polyarthritis, 29.8% other categories) and 98 healthy children, were
      enrolled in three centres. The JAMAR components discriminated well healthy
      subjects from JIA patients. All JAMAR components revealed good psychometric
      performances. In conclusion, the American English version of the JAMAR is a valid
      tool for the assessment of children with JIA and is suitable for use both in
      routine clinical practice and clinical research.

PMID- 29637339
TI  - The Danish version of the Juvenile Arthritis Multidimensional Assessment Report
      (JAMAR).
AB  - The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new
      parent/patient-reported outcome measure that enables a thorough assessment of the
      disease status in children with juvenile idiopathic arthritis (JIA). We report
      the results of the cross-cultural adaptation and validation of the parent and
      patient versions of the JAMAR in the Danish language. The reading comprehension
      of the questionnaire was tested in ten JIA parents and patients. Each
      participating centre was asked to collect demographic, clinical data and the
      JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6
      month period and to administer the JAMAR to 100 healthy children and their
      parents. The statistical validation phase explored descriptive statistics and the
      psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling
      effects, internal consistency, Cronbach's alpha, interscale correlations, test
      retest reliability and construct validity (convergent and discriminant validity).
      A total of 303 JIA patients (7.9% systemic, 35% oligoarticular, 22.1% RF negative
      polyarthritis, 35% other categories) and 99 healthy children, were enrolled in
      three centres. The JAMAR components discriminated well healthy subjects from JIA
      patients. All JAMAR components revealed good psychometric performances. In
      conclusion, the Danish version of the JAMAR is a valid tool for the assessment of
      children with JIA and is suitable for use both in routine clinical practice and
      clinical research.

PMID- 29637340
TI  - The Afrikaans version of the Juvenile Arthritis Multidimensional Assessment
      Report (JAMAR).
AB  - The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new
      parent/patient reported outcome measure that enables a thorough assessment of the
      disease status in children with juvenile idiopathic arthritis (JIA). We report
      the results of the cross-cultural adaptation and validation of the parent and
      patient versions of the JAMAR in the Afrikaans language. The reading
      comprehension of the questionnaire was tested in ten JIA parents and patients.
      Each participating centre was asked to collect demographic, clinical data and the
      JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6
      month period and to administer the JAMAR to 100 healthy children and their
      parents. The statistical validation phase explored descriptive statistics and the
      psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling
      effects, internal consistency, Cronbach's alpha, interscale correlations, test
      retest reliability, and construct validity (convergent and discriminant
      validity). A total of 91 JIA patients (4.4% systemic JIA, 35.1% oligoarticular,
      23.1% RF negative polyarthritis, 37.4% other categories), and 98 healthy children
      were enrolled in one paediatric rheumatology centre. The JAMAR components
      discriminated well healthy subjects from JIA patients. All JAMAR components
      revealed satisfactory psychometric performances. In conclusion, the Afrikaans
      version of the JAMAR is a valid tool for the assessment of children with JIA and
      is suitable for use both in routine clinical practice and in clinical research.

PMID- 29637341
TI  - The Hungarian version of the Juvenile Arthritis Multidimensional Assessment
      Report (JAMAR).
AB  - The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new
      parent/patient-reported outcome measure that enables a thorough assessment of the
      disease status in children with juvenile idiopathic arthritis (JIA). We report
      the results of the cross-cultural adaptation and validation of the parent and
      patient versions of the JAMAR in the Hungarian language. The reading
      comprehension of the questionnaire was tested in 10 JIA parents and patients.
      Each participating centre was asked to collect demographic, clinical data and the
      JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6
      month period and to administer the JAMAR to 100 healthy children and their
      parents. The statistical validation phase explored descriptive statistics and the
      psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling
      effects, internal consistency, Cronbach's alpha, interscale correlations, test
      retest reliability, and construct validity (convergent and discriminant
      validity). A total of 206 JIA patients (3.9% systemic, 41.3% oligoarticular,
      28.2% RF-negative polyarthritis, 26.6% other categories) and 90 healthy children,
      were enrolled in two centres. The JAMAR components discriminated healthy subjects
      from JIA patients. All JAMAR components revealed good psychometric performances.
      In conclusion, the Hungarian version of the JAMAR is a valid tool for the
      assessment of children with JIA and is suitable for use both in routine clinical
      practice and clinical research.

PMID- 29637342
TI  - The Mexican Spanish version of the Juvenile Arthritis Multidimensional Assessment
      Report (JAMAR).
AB  - The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new
      parent/patient reported outcome measure that enables a thorough assessment of the
      disease status in children with juvenile idiopathic arthritis (JIA). We report
      the results of the cross-cultural adaptation and validation of the parent and
      patient versions of the JAMAR in the Mexican Spanish language. The reading
      comprehension of the questionnaire was tested in 10 JIA parents and patients.
      Each participating centre was asked to collect demographic, clinical data and the
      JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6
      month period and to administer the JAMAR to 100 healthy children and their
      parents. The statistical validation phase explored descriptive statistics and the
      psychometric issues of the JAMAR: the 3 Likert assumptions, floor/ceiling
      effects, internal consistency, Cronbach's alpha, interscale correlations, test
      retest reliability, and construct validity (convergent and discriminant
      validity). A total of 100 JIA patients (16% systemic, 16% oligoarticular, 30% RF
      positive polyarthritis, 38% other categories) and 99 healthy children, were
      enrolled at the paediatric rheumatology department of the Hospital General de
      Mexico. The JAMAR components discriminated well healthy subjects from JIA
      patients. However, there was no significant difference between healthy subjects
      and their affected peers in school related problem variable. All JAMAR components
      revealed good psychometric performances. In conclusion, the Mexican Spanish
      version of the JAMAR is a valid tool for the assessment of children with JIA and
      is suitable for use both in routine clinical practice and clinical research.

PMID- 29637343
TI  - The Serbian version of the Juvenile Arthritis Multidimensional Assessment Report
      (JAMAR).
AB  - The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new
      parent/patient-reported outcome measure that enables a thorough assessment of the
      disease status in children with juvenile idiopathic arthritis (JIA). We report
      the results of the cross-cultural adaptation and validation of the parent and
      patient versions of the JAMAR in the Serbian language. The reading comprehension
      of the questionnaire was tested in 10 JIA parents and patients. Each
      participating centre was asked to collect demographic, clinical data and the
      JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6
      month period and to administer the JAMAR to 100 healthy children and their
      parents. The statistical validation phase explored descriptive statistics and the
      psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling
      effects, internal consistency, Cronbach's alpha, interscale correlations, test
      retest reliability, and construct validity (convergent and discriminant
      validity). A total of 248 JIA patients (5.2% systemic, 44.3% oligoarticular,
      23.8% RF-negative polyarthritis, 26.7% other categories) and 100 healthy children
      were enrolled in three centres. The JAMAR components discriminated healthy
      subjects from JIA patients. All JAMAR components revealed good psychometric
      performances. In conclusion, the Serbian version of the JAMAR is a valid tool for
      the assessment of children with JIA and is suitable for use both in routine
      clinical practice and clinical research.

PMID- 29637344
TI  - The Dutch version of the Juvenile Arthritis Multidimensional Assessment Report
      (JAMAR).
AB  - The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new
      parent/patient reported outcome measure that enables a thorough assessment of the
      disease status in children with juvenile idiopathic arthritis (JIA). We report
      the results of the cross-cultural adaptation and validation of the parent and
      patient versions of the JAMAR in the Dutch language. The reading comprehension of
      the questionnaire was tested in ten JIA parents and patients. Each participating
      centre was asked to collect demographic, clinical data and the JAMAR in 100
      consecutive JIA patients or all consecutive patients seen in a 6-month period and
      to administer the JAMAR to 100 healthy children and their parents. The
      statistical validation phase explored descriptive statistics and the psychometric
      issues of the JAMAR: the three Likert assumptions, floor/ceiling effects,
      internal consistency, Cronbach's alpha, interscale correlations, test-retest
      reliability, and construct validity (convergent and discriminant validity). A
      total of 209 JIA patients (14.3% systemic, 39.7% oligoarticular, 25.8% RF
      negative polyarthritis, 20.2% other categories) and 107 healthy children were
      enrolled in two centres. The JAMAR components discriminated well healthy subjects
      from JIA patients. All JAMAR components revealed good psychometric performances.
      In conclusion, the Dutch version of the JAMAR is a valid tool for the assessment
      of children with JIA and is suitable for use both in routine clinical practice
      and clinical research.

PMID- 29637345
TI  - The Slovene version of the Juvenile Arthritis Multidimensional Assessment Report
      (JAMAR).
AB  - The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new
      parent/patient reported outcome measure that enables a thorough assessment of the
      disease status in children with juvenile idiopathic arthritis (JIA). We report
      the results of the cross-cultural adaptation and validation of the parent and
      patient versions of the JAMAR in the Slovene language. The reading comprehension
      of the questionnaire was tested in 10 JIA parents and patients. Each
      participating centre was asked to collect demographic, clinical data and the
      JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6
      month period and to administer the JAMAR to 100 healthy children and their
      parents. The statistical validation phase explored descriptive statistics and the
      psychometric issues of the JAMAR: the 3 Likert assumptions, floor/ceiling
      effects, internal consistency, Cronbach's alpha, interscale correlations, test
      retest reliability, and construct validity (convergent and discriminant
      validity). A total of 100 JIA patients (7.0% systemic, 47.0% oligoarticular,
      22.0% RF negative polyarthritis, 24.0% other categories) and 120 healthy
      children, were enrolled. The JAMAR components discriminated well healthy subjects
      from JIA patients, except for the Health-Related Quality of Life, Psychosocial
      Health subscales. All JAMAR components revealed good psychometric performances.
      In conclusion, the Slovene version of the JAMAR is a valid tool for the
      assessment of children with JIA and is suitable for use both in routine clinical
      practice and clinical research.

PMID- 29637346
TI  - The Swedish version of the Juvenile Arthritis Multidimensional Assessment Report
      (JAMAR).
AB  - The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new
      parent/patient-reported outcome measure that enables a thorough assessment of the
      disease status in children with juvenile idiopathic arthritis (JIA). We report
      the results of the cross-cultural adaptation and validation of the parent and
      patient versions of the JAMAR in the Swedish language. The reading comprehension
      of the questionnaire was tested in 10 JIA parents and patients. Each
      participating centre was asked to collect demographic, clinical data and the
      JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6
      month period and to administer the JAMAR to 100 healthy children and their
      parents. The statistical validation phase explored descriptive statistics and the
      psychometric issues of the JAMAR: the 3 Likert assumptions, floor/ceiling
      effects, internal consistency, Cronbach's alpha, interscale correlations, test
      retest reliability and construct validity (convergent and discriminant validity).
      A total of 68 JIA patients (8.8% systemic, 44.1% oligoarticular, 13.2% RF
      negative polyarthritis, 33.9% other categories) and 76 healthy children, were
      enrolled in two centres. The JAMAR components discriminated well healthy subjects
      from JIA patients. All JAMAR components revealed good psychometric performances.
      In conclusion, the Swedish version of the JAMAR is a valid tool for the
      assessment of children with JIA and is suitable for use both in routine clinical
      practice and clinical research.

PMID- 29637347
TI  - The Latvian version of the Juvenile Arthritis Multidimensional Assessment Report
      (JAMAR).
AB  - The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new
      parent/patient reported outcome measure that enables a thorough assessment of the
      disease status in children with juvenile idiopathic arthritis (JIA). We report
      the results of the cross-cultural adaptation and validation of the parent and
      patient versions of the JAMAR in the Latvian language. The reading comprehension
      of the questionnaire was tested in 10 JIA parents and patients. Each
      participating centre was asked to collect demographic, clinical data and the
      JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6
      month period and to administer the JAMAR to 100 healthy children and their
      parents. The statistical validation phase explored descriptive statistics and the
      psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling
      effects, internal consistency, Cronbach's alpha, interscale correlations, test
      retest reliability, and construct validity (convergent and discriminant
      validity). A total of 100 JIA patients (2% systemic, 56% oligoarticular, 17% RF
      negative polyarthritis, 25% other categories) and 204 healthy children, were
      enrolled at the paediatric rheumatology centre. The JAMAR components
      discriminated healthy subjects from JIA patients, except for the paediatric
      rheumatology quality of life (HRQoL), psychosocial health (PsH) subscales, the
      HRQoL total score and for the school-related problems variable. All JAMAR
      components revealed good psychometric performances. In conclusion, the Latvian
      version of the JAMAR is a valid tool for the assessment of children with JIA and
      is suitable for use both in routine clinical practice and clinical research.

PMID- 29637348
TI  - The Egyptian Arabic version of the Juvenile Arthritis Multidimensional Assessment
      Report (JAMAR).
AB  - The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new
      parent/patient-reported outcome measure that enables a thorough assessment of the
      disease status in children with juvenile idiopathic arthritis (JIA). We report
      the results of the cross-cultural adaptation and validation of the parent and
      patient versions of the JAMAR in the Egyptian Arabic language. The reading
      comprehension of the questionnaire was tested in ten JIA parents and patients.
      Each participating centre was asked to collect demographic, clinical data and the
      JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6
      month period and to administer the JAMAR to 100 healthy children and their
      parents. The statistical validation phase explored descriptive statistics and the
      psychometric issues of the JAMAR: the 3 Likert assumptions, floor/ceiling
      effects, internal consistency, Cronbach's alpha, interscale correlations, test
      retest reliability, and construct validity (convergent and discriminant
      validity). A total of 100 JIA patients (20.0% systemic JIA, 40.0%
      undifferentiated arthritis, 24.0% RF negative polyarthritis, 16.0% other
      categories) and 100 healthy children were enrolled in one paediatric rheumatology
      centre. The JAMAR components discriminated well healthy subjects from JIA
      patients. All JAMAR components revealed satisfactory psychometric performances.
      In conclusion, the Egyptian Arabic version of the JAMAR is a valid tool for the
      assessment of children with JIA and is suitable for use both in routine clinical
      practice and in clinical research.

PMID- 29637349
TI  - The Brazilian Portuguese version of the Juvenile Arthritis Multidimensional
      Assessment Report (JAMAR).
AB  - The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new
      parent/patient reported outcome measure that enables a thorough assessment of the
      disease status in children with juvenile idiopathic arthritis (JIA). We report
      the results of the cross-cultural adaptation and validation of the parent and
      patient versions of the JAMAR in the Brazilian Portuguese language. The reading
      comprehension of the questionnaire was tested in 10 JIA parents and patients.
      Each participating centre was asked to collect demographic, clinical data and the
      JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6
      month period and to administer the JAMAR to 100 healthy children and their
      parents. The statistical validation phase explored descriptive statistics and the
      psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling
      effects, internal consistency, Cronbach's alpha, interscale correlations, test
      retest reliability, and construct validity (convergent and discriminant
      validity). A total of 231 JIA patients (14.7% systemic, 43.3% oligoarticular,
      22.5% RF negative polyarthritis, 19.5% other categories) and 72 healthy children,
      were enrolled in three centres. The JAMAR components discriminated well healthy
      subjects from JIA patients. All JAMAR components revealed good psychometric
      performances. In conclusion, the Brazilian Portuguese version of the JAMAR is a
      valid tool for the assessment of children with JIA and is suitable for use both
      in routine clinical practice and clinical research.

PMID- 29637350
TI  - The Czech version of the Juvenile Arthritis Multidimensional Assessment Report
      (JAMAR).
AB  - The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new
      parent/patient-reported outcome measure that enables a thorough assessment of the
      disease status in children with juvenile idiopathic arthritis (JIA). We report
      results of the cross-cultural adaptation and validation of the parent and patient
      versions of the JAMAR in the Czech language. The reading comprehension of the
      questionnaire was tested in ten JIA parents and patients. The participating
      centre was asked to collect demographic and clinical data along the JAMAR
      questionnaire in 100 consecutive JIA patients or all consecutive patients seen in
      a 6-month period and to administer the JAMAR to 100 healthy children and their
      parents. The statistical validation phase explored descriptive statistics and the
      psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling
      effects, internal consistency, Cronbach's alpha, interscale correlations, test
      retest reliability, and construct validity (convergent and discriminant
      validity). A total of 103 JIA patients (5.8% systemic, 35.9% oligoarticular,
      37.9% RF-negative polyarthritis, 20.4% other categories) and 100 healthy
      children, were enrolled. The JAMAR components discriminated well healthy subjects
      from JIA patients. Notably, there was no significant difference between healthy
      subjects and their affected peers in the school-related problems variable and in
      the Psychosocial Health of the Paediatric Rheumatology Quality of Life scale. All
      JAMAR components revealed good psychometric performances. In conclusion, the
      Czech version of the JAMAR is a valid tool for the assessment of children with
      JIA and is suitable for use both in routine clinical practice and clinical
      research.

PMID- 29637351
TI  - The Arabic version of the Juvenile Arthritis Multidimensional Assessment Report
      (JAMAR).
AB  - The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new
      parent/patient reported outcome measure that enables a thorough assessment of the
      disease status in children with juvenile idiopathic arthritis (JIA). We report
      the results of the cross-cultural adaptation and validation of the parent and
      patient versions of the JAMAR in the Arabic language. The reading comprehension
      of the questionnaire was tested in 10 JIA parents and patients. Each
      participating centre was asked to collect demographic and clinical data and the
      JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6
      month period and to administer the JAMAR to 100 healthy children and their
      parents. The statistical validation phase explored descriptive statistics and the
      psychometric issues of the JAMAR: the 3 Likert assumptions, floor/ceiling
      effects, internal consistency, Cronbach's alpha, interscale correlations, test
      retest reliability, and construct validity (convergent and discriminant
      validity). A total of 100 JIA patients (27.0% systemic JIA, 23.0% oligoarticular,
      25.0% RF negative polyarthritis, and 25.0% other categories) and 100 healthy
      children, were enrolled in one paediatric rheumatology centre. The JAMAR
      components discriminated well healthy subjects from JIA patients. All JAMAR
      components revealed satisfactory psychometric performances. In conclusion, the
      Arabic version of the JAMAR is a valid tool for the assessment of children with
      JIA and is suitable for use both in routine clinical practice and in clinical
      research.

PMID- 29637352
TI  - The Ukrainian version of the Juvenile Arthritis Multidimensional Assessment
      Report (JAMAR).
AB  - The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new
      parent/patient-reported outcome measure that enables a thorough assessment of the
      disease status in children with juvenile idiopathic arthritis (JIA). We report
      the results of the cross-cultural adaptation and validation of the parent and
      patient versions of the JAMAR in the Ukrainian language. The reading
      comprehension of the questionnaire was tested in 10 JIA parents and patients.
      Each participating centre was asked to collect demographic, clinical data and the
      JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6
      month period and to administer the JAMAR to 100 healthy children and their
      parents. The statistical validation phase explored descriptive statistics and the
      psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling
      effects, internal consistency, Cronbach's alpha, interscale correlations, test
      retest reliability, and construct validity (convergent and discriminant
      validity). A total of 100 JIA patients (2% systemic, 44% oligoarticular, 20% RF
      negative polyarthritis, 34% other categories) and 100 healthy children were
      enrolled at the paediatric rheumatology centre of the Western Ukrainian
      Specialised Children's Medical Centre. The JAMAR components discriminated well
      between healthy subjects and JIA patients. Notably, there was no significant
      difference between healthy subjects and their affected peers in the school
      related problems variable. All JAMAR components revealed good psychometric
      performances. In conclusion, the Ukrainian version of the JAMAR is a valid tool
      for the assessment of children with JIA and is suitable for use both in routine
      clinical practice and clinical research.

PMID- 29637353
TI  - The Lithuanian version of the Juvenile Arthritis Multidimensional Assessment
      Report (JAMAR).
AB  - The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new
      parent/patient reported outcome measure that enables a thorough assessment of the
      disease status in children with juvenile idiopathic arthritis (JIA). We report
      the results of the cross-cultural adaptation and validation of the parent and
      patient versions of the JAMAR in the Lithuanian language. The reading
      comprehension of the questionnaire was tested in ten JIA parents and patients.
      Each participating centre was asked to collect demographic, clinical data and the
      JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6
      month period and to administer the JAMAR to 100 healthy children and their
      parents. The statistical validation phase explored descriptive statistics and the
      psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling
      effects, internal consistency, Cronbach's alpha, interscale correlations, test
      retest reliability, and construct validity (convergent and discriminant
      validity). A total of 101 JIA patients (5.9% systemic, 38.6% oligoarticular,
      23.8% RF negative polyarthritis, 31.7% other categories) and 116 healthy
      children, were enrolled at the paediatric rheumatology centre in Vilnius. The
      JAMAR components discriminated well healthy subjects from JIA patients. Notably,
      there is no significant difference between healthy subjects and their affected
      peers in the school-related problems variable. All JAMAR components revealed good
      psychometric performances. In conclusion, the Lithuanian version of the JAMAR is
      a valid tool for the assessment of children with JIA and is suitable for use both
      in routine clinical practice and clinical research.

PMID- 29637354
TI  - The Swiss French version of the Juvenile Arthritis Multidimensional Assessment
      Report (JAMAR).
AB  - The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new
      parent/patient reported outcome measure that enables a thorough assessment of the
      disease status in children with juvenile idiopathic arthritis (JIA). We report
      the results of the cross-cultural adaptation and validation of the parent and
      patient versions of the JAMAR in the Swiss French language. The reading
      comprehension of the questionnaire was tested in ten JIA parents and patients.
      Each participating centre was asked to collect demographic, clinical data, and
      the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6
      month period and to administer the JAMAR to 100 healthy children and their
      parents. The statistical validation phase explored descriptive statistics and the
      psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling
      effects, internal consistency, Cronbach's alpha, interscale correlations, test
      retest reliability, and construct validity (convergent and discriminant
      validity). A total of 98 JIA patients (3.1% systemic, 43.9% oligoarticular, 16.3%
      RF negative polyarthritis, 36.7% other categories), and 64 healthy children were
      enrolled in a paediatric rheumatology centre. The JAMAR components discriminated
      well healthy subjects from JIA patients. All JAMAR components revealed good
      psychometric performances. In conclusion, the Swiss French version of the JAMAR
      is a valid tool for the assessment of children with JIA and is suitable for use
      both in routine clinical practice and clinical research.

PMID- 29637355
TI  - The Hebrew version of the Juvenile Arthritis Multidimensional Assessment Report
      (JAMAR).
AB  - The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new
      parent/patient reported outcome measure that enables a thorough assessment of the
      disease status in children with juvenile idiopathic arthritis (JIA). We report
      the results of the cross-cultural adaptation and validation of the parent and
      patient versions of the JAMAR in the Hebrew language. The reading comprehension
      of the questionnaire was tested in ten JIA parents and patients. Each
      participating centre was asked to collect demographic, clinical data, and the
      JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6
      month period and to administer the JAMAR to 100 healthy children and their
      parents. The statistical validation phase explored descriptive statistics and the
      psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling
      effects, internal consistency, Cronbach's alpha, interscale correlations, and
      construct validity (convergent and discriminant validity). A total of 116 JIA
      patients (17.2% systemic, 56% oligoarticular, 20.7% RF negative poly-arthritis,
      and 6.1% other categories) and 98 healthy children were enrolled in two centres.
      The JAMAR components discriminated well healthy subjects from JIA patients. All
      JAMAR components revealed good psychometric performances. In conclusion, the
      Hebrew version of the JAMAR is a valid tool for the assessment of children with
      JIA and is suitable for use both in routine clinical practice and in clinical
      research.

PMID- 29637356
TI  - The French version of the Juvenile Arthritis Multidimensional Assessment Report
      (JAMAR).
AB  - The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new
      parent/patient reported outcome measure that enables a thorough assessment of the
      disease status in children with juvenile idiopathic arthritis (JIA). We report
      the results of the cross-cultural adaptation and validation of the parent and
      patient versions of the JAMAR in the French language. The reading comprehension
      of the questionnaire was tested in 10 JIA parents and patients. Each
      participating centre was asked to collect demographic, clinical data and the
      JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6
      month period and to administer the JAMAR to 100 healthy children and their
      parents. The statistical validation phase explored descriptive statistics and the
      psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling
      effects, internal consistency, Cronbach's alpha, interscale correlations and
      construct validity (convergent and discriminant validity). A total of 100 JIA
      patients (23% systemic, 45% oligoarticular, 20% RF negative polyarthritis, 12%
      other categories) and 122 healthy children, were enrolled at the paediatric
      rheumatology centre of the Necker Children's Hospital in Paris. Notably, none of
      the enrolled JIA patients is affected with psoriatic arthritis. The JAMAR
      components discriminated well healthy subjects from JIA patients. All JAMAR
      components revealed good psychometric performances. In conclusion, the French
      version of the JAMAR is a valid tool for the assessment of children with JIA and
      is suitable for use both in routine clinical practice and clinical research.

PMID- 29637357
TI  - The British English version of the Juvenile Arthritis Multidimensional Assessment
      Report (JAMAR).
AB  - The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new
      parent/patient-reported outcome measure that enables a thorough assessment of the
      disease status in children with juvenile idiopathic arthritis (JIA). We report
      the results of the cross-cultural adaptation and validation of the parent and
      patient versions of the JAMAR in the British English language. The reading
      comprehension of the questionnaire was tested in ten JIA parents and patients.
      Each participating centre was asked to collect demographic, clinical data and the
      JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6
      month period and to administer the JAMAR to 100 healthy children and their
      parents. The statistical validation phase explored descriptive statistics and the
      psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling
      effects, internal consistency, Cronbach's alpha, interscale correlations, test
      retest reliability, and construct validity (convergent and discriminant
      validity). A total of 100 JIA patients (7.0% systemic, 38.0% oligoarticular,
      27.0% RF negative polyarthritis, 28% other categories) and 100 healthy children,
      were enrolled at the Royal Hospital for Sick Children in Glasgow. The JAMAR
      components discriminated well healthy subjects from JIA patients. All JAMAR
      components revealed good psychometric performances. In conclusion, the British
      English version of the JAMAR is a valid tool for the assessment of children with
      JIA and is suitable for use both in routine clinical practice and clinical
      research.

PMID- 29637358
TI  - The Polish version of the Juvenile Arthritis Multidimensional Assessment Report
      (JAMAR).
AB  - The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new
      parent/patient-reported outcome measure that enables a thorough assessment of the
      disease status in children with juvenile idiopathic arthritis (JIA). We report
      the results of the cross-cultural adaptation and validation of the parent and
      patient versions of the JAMAR in the Polish language. The reading comprehension
      of the questionnaire was tested in 10 JIA parents and patients. Each
      participating centre was asked to collect demographic, clinical data and the
      JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6
      month period and to administer the JAMAR to 100 healthy children and their
      parents. The statistical validation phase explored descriptive statistics and the
      psychometric issues of the JAMAR: the 3 Likert assumptions, floor/ceiling
      effects, internal consistency, Cronbach's alpha, interscale correlations, test
      retest reliability, and construct validity (convergent and discriminant
      validity). A total of 154 JIA patients (10.4% systemic, 50.0% oligoarticular,
      24.7% RF-negative polyarthritis, 14.9% other categories) and 91 healthy children,
      were enrolled in two centres. The JAMAR components discriminated well healthy
      subjects from JIA patients. All JAMAR components revealed good psychometric
      performances. In conclusion, the Polish version of the JAMAR is a valid tool for
      the assessment of children with JIA and is suitable for use both in routine
      clinical practice and clinical research.

PMID- 29637359
TI  - The Algerian Arabic version of the Juvenile Arthritis Multidimensional Assessment
      Report (JAMAR).
AB  - The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new
      parent/patient-reported outcome measure that enables a thorough assessment of the
      disease status in children with juvenile idiopathic arthritis (JIA). We report
      the results of the cross-cultural adaptation and validation of the parent and
      patient versions of the JAMAR in the Algerian Arabic language. The reading
      comprehension of the questionnaire was tested in ten JIA parents and patients.
      Each participating centre was asked to collect demographic, clinical data and the
      JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6
      month period and to administer the JAMAR to 100 healthy children and their
      parents. The statistical validation phase explored descriptive statistics and the
      psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling
      effects, internal consistency, Cronbach's alpha, interscale correlations, test
      retest reliability, and construct validity (convergent and discriminant
      validity). A total of 70 JIA patients (10.0% systemic, 35.7.0% oligoarticular,
      21.4% RF negative polyarthritis, 32.9% other categories) and 70 healthy children,
      were enrolled in a paediatric rheumatology centre. The JAMAR components
      discriminated well healthy subjects from JIA patients. All JAMAR components
      revealed satisfactory psychometric performances. In conclusion, the Algerian
      Arabic version of the JAMAR is a valid tool for the assessment of children with
      JIA and is suitable for use both in routine clinical practice and clinical
      research.

PMID- 29637360
TI  - The Thai version of the Juvenile Arthritis Multidimensional Assessment Report
      (JAMAR).
AB  - The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new
      parent/patient-reported outcome measure that enables a thorough assessment of the
      disease status in children with juvenile idiopathic arthritis (JIA). We report
      the results of the cross-cultural adaptation and validation of the parent and
      patient versions of the JAMAR in the Thai language. The reading comprehension of
      the questionnaire was tested in ten JIA parents and patients. Each participating
      centre was asked to collect demographic, clinical data and the JAMAR in 100
      consecutive JIA patients or all consecutive patients seen in a 6-month period and
      to administer the JAMAR to 100 healthy children and their parents. The
      statistical validation phase explored descriptive statistics and the psychometric
      issues of the JAMAR: the three Likert assumptions, floor/ceiling effects,
      internal consistency, Cronbach's alpha, interscale correlations, test-retest
      reliability, and construct validity (convergent and discriminant validity). A
      total of 104 JIA patients (45.2% systemic JIA, 10.6% oligoarticular, 9.6% RF
      negative polyarthritis, 34.6% other categories) and 102 healthy children, were
      enrolled in one paediatric rheumatology centre. Notably, none of the enrolled JIA
      patients is affected with psoriatic arthritis or undifferentiated arthritis. The
      JAMAR components discriminated well healthy subjects from JIA patients. All JAMAR
      components revealed satisfactory psychometric performances. In conclusion, the
      Thai version of the JAMAR is a valid tool for the assessment of children with JIA
      and is suitable for use both in routine clinical practice and clinical research.

PMID- 29637361
TI  - The Slovak version of the Juvenile Arthritis Multidimensional Assessment Report
      (JAMAR).
AB  - The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new
      parent/patient-reported outcome measure that enables a thorough assessment of the
      disease status in children with juvenile idiopathic arthritis (JIA). We report
      the results of the cross-cultural adaptation and validation of the parent and
      patient versions of the JAMAR in the Slovak language. The reading comprehension
      of the questionnaire was tested in 10 JIA parents and patients. Each
      participating centre was asked to collect demographic, clinical data and the
      JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6
      month period and to administer the JAMAR to 100 healthy children and their
      parents. The statistical validation phase explored descriptive statistics and the
      psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling
      effects, internal consistency, Cronbach's alpha, interscale correlations, test
      retest reliability, and construct validity (convergent and discriminant
      validity). A total of 108 JIA patients (5.6% systemic, 38.9% oligoarticular,
      30.5% RF-negative polyarthritis, 25% other categories) and 100 healthy children
      were enrolled in two centres. Notably, none of the enrolled JIA patients is
      affected with psoriatic arthritis. The JAMAR components discriminated healthy
      subjects from JIA patients. All JAMAR components revealed good psychometric
      performances. In conclusion, the Slovak version of the JAMAR is a valid tool for
      the assessment of children with JIA and is suitable for use both in routine
      clinical practice and clinical research.

PMID- 29637362
TI  - The Flemish version of the Juvenile Arthritis Multidimensional Assessment Report
      (JAMAR).
AB  - The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new
      parent/patient reported outcome measure that enables a thorough assessment of the
      disease status in children with juvenile idiopathic arthritis (JIA). We report
      the results of the cross-cultural adaptation and validation of the parent and
      patient versions of the JAMAR in the Flemish language. The reading comprehension
      of the questionnaire was tested in 10 JIA parents and patients. Each
      participating centre was asked to collect demographic, clinical data and the
      JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6
      month period and to administer the JAMAR to 100 healthy children and their
      parents. The statistical validation phase explored descriptive statistics and the
      psychometric issues of the JAMAR: the 3 Likert assumptions, floor/ceiling
      effects, internal consistency, Cronbach's alpha, interscale correlations, test
      retest reliability, and construct validity (convergent and discriminant
      validity). A total of 100 JIA patients (8% systemic, 33% oligoarticular, 24% RF
      negative polyarthritis, 35% other categories) and 99 healthy children, were
      enrolled in two centres. The JAMAR components discriminated well healthy subjects
      from JIA patients. All JAMAR components revealed good psychometric performances.
      In conclusion, the Flemish version of the JAMAR is a valid tool for the
      assessment of children with JIA and is suitable for use both in routine clinical
      practice and clinical research.

PMID- 29637364
TI  - The Portuguese version of the Juvenile Arthritis Multidimensional Assessment
      Report (JAMAR).
AB  - The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new
      parent/patient reported outcome measure that enables a thorough assessment of the
      disease status in children with juvenile idiopathic arthritis (JIA). We report
      the results of the cross-cultural adaptation and validation of the parent and
      patient versions of the JAMAR in the Portuguese language. The reading
      comprehension of the questionnaire was tested in 10 JIA parents and patients.
      Each participating centre was asked to collect demographic, clinical data and the
      JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6
      month period and to administer the JAMAR to 100 healthy children and their
      parents. The statistical validation phase explored descriptive statistics and the
      psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling
      effects, internal consistency, Cronbach's alpha, interscale correlations, and
      construct validity (convergent and discriminant validity). A total of 80 JIA
      patients (6.3% systemic, 68.8% oligoarticular, 3.7% RF negative polyarthritis,
      21.2% other categories) and 30 healthy children were enrolled. The JAMAR
      components discriminated well healthy subjects from JIA patients. All JAMAR
      components revealed good psychometric performances. Notably, there was no
      significant difference between healthy subjects and their affected peers in
      school-related items. In conclusion, the Portuguese version of the JAMAR is a
      valid tool for the assessment of children with JIA and is suitable for use both
      in routine clinical practice and clinical research.

PMID- 29637363
TI  - The Estonian version of the Juvenile Arthritis Multidimensional Assessment Report
      (JAMAR).
AB  - The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new
      parent/patient-reported outcome measure that enables a thorough assessment of the
      disease status in children with juvenile idiopathic arthritis (JIA). We report
      the results of the cross-cultural adaptation and validation of the parent and
      patient versions of the JAMAR in the Estonian language. The reading comprehension
      of the questionnaire was tested in 10 JIA parents and patients. Each
      participating centre was asked to collect demographic, clinical data and the
      JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6
      month period and to administer the JAMAR to 100 healthy children and their
      parents. The statistical validation phase explored descriptive statistics and the
      psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling
      effects, internal consistency, Cronbach's alpha, interscale correlations, test
      retest reliability, and construct validity (convergent and discriminant
      validity). A total of 110 JIA patients (71.8% oligoarticular, 18.2% RF-negative
      polyarthritis, 10% other categories) and 98 healthy children were enrolled in one
      paediatric rheumatology centre. Notably, none of the enrolled JIA patients is
      affected with systemic JIA. The JAMAR components discriminated healthy subjects
      from JIA patients, except for the Paediatric Rheumatology Quality of Life (HRQoL)
      Psychosocial Health (PsH) subscales and for the satisfaction with current health
      status. All JAMAR components revealed good psychometric performances. In
      conclusion, the Estonian version of the JAMAR is a valid tool for the assessment
      of children with JIA and is suitable for use both in routine clinical practice
      and clinical research.

PMID- 29637365
TI  - The Ecuadorian Spanish version of the Juvenile Arthritis Multidimensional
      Assessment Report (JAMAR).
AB  - The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new
      parent/patient reported outcome measure that enables a thorough assessment of the
      disease status in children with juvenile idiopathic arthritis (JIA). We report
      the results of the cross-cultural adaptation and validation of the parent and
      patient versions of the JAMAR in the Ecuadorian Spanish language. The reading
      comprehension of the questionnaire was tested in 10 JIA parents and patients.
      Each participating centre was asked to collect demographic, clinical data and the
      JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6
      month period and to administer the JAMAR to 100 healthy children and their
      parents. The statistical validation phase explored descriptive statistics and the
      psychometric issues of the JAMAR: the 3 Likert assumptions, floor/ceiling
      effects, internal consistency, Cronbach's alpha, interscale correlations, test
      retest reliability, and construct validity (convergent and discriminant
      validity). A total of 23 JIA patients (17.4% systemic, 17.4% RF negative poly
      arthritis, 17.4% RF positive poly-arthritis, and 47.8% other categories) and 23
      healthy children were enrolled in the paediatric centre of Guayaquil. The JAMAR
      components discriminated well healthy subjects from JIA patients. Notably, there
      is no significant difference between the healthy subjects and their affected
      peers in the school-related problems variable. All JAMAR components revealed good
      psychometric performances. In conclusion, the Ecuadorian Spanish version of the
      JAMAR is a valid tool for the assessment of children with JIA and is suitable for
      use both in routine clinical practice and clinical research.

PMID- 29637366
TI  - The Farsi version of the Juvenile Arthritis Multidimensional Assessment Report
      (JAMAR).
AB  - The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new
      parent/patient reported outcome measure that enables a thorough assessment of the
      disease status in children with juvenile idiopathic arthritis (JIA). We report
      the results of the cross-cultural adaptation and validation of the parent and
      patient versions of the JAMAR in the Farsi language. The reading comprehension of
      the questionnaire was tested in 10 JIA parents and patients. Each participating
      centre was asked to collect demographic, clinical data and the JAMAR in 100
      consecutive JIA patients or all consecutive patients seen in a 6-month period and
      to administer the JAMAR to 100 healthy children and their parents. The
      statistical validation phase explored descriptive statistics and the psychometric
      issues of the JAMAR: the three Likert assumptions, floor/ceiling effects,
      internal consistency, Cronbach's alpha, interscale correlations, test-retest
      reliability, and construct validity (convergent and discriminant validity). A
      total of 102 JIA patients (14.7% systemic JIA, 67.6% oligoarticular, 15.7% RF
      negative polyarthritis, 2.0% other categories) and 198 healthy children, were
      enrolled in three paediatric rheumatology centres. Notably, none of the enrolled
      JIA patients is affected with enthesitis-related arthritis or undifferentiated
      arthritis. The JAMAR components discriminated healthy subjects from JIA patients.
      All JAMAR components revealed satisfactory psychometric performances. In
      conclusion, the Farsi version of the JAMAR is a valid tool for the assessment of
      children with JIA and is suitable for use both in routine clinical practice and
      clinical research.

PMID- 29637367
TI  - The Omani Arabic version of the Juvenile Arthritis Multidimensional Assessment
      Report (JAMAR).
AB  - The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new
      parent/patient reported outcome measure that enables a thorough assessment of the
      disease status in children with juvenile idiopathic arthritis (JIA). We report
      the results of the cross-cultural adaptation and validation of the parent and
      patient versions of the JAMAR in the Omani Arabic language. The reading
      comprehension of the questionnaire was tested in 10 JIA parents and patients.
      Each participating centre was asked to collect demographic, clinical data and the
      JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6
      month period and to administer the JAMAR to 100 healthy children and their
      parents. The statistical validation phase explored descriptive statistics and the
      psychometric issues of the JAMAR: the 3 Likert assumptions, floor/ceiling
      effects, internal consistency, Cronbach's alpha, interscale correlations, test
      retest reliability, and construct validity (convergent and discriminant
      validity). A total of 57 JIA patients (22.8% systemic, 28.1% oligoarticular,
      35.1% RF negative polyarthritis, 14.0% other categories) and 85 healthy children,
      were enrolled in two centres. Notably, none of the enrolled JIA patients is
      affected with enthesitis-related arthritis or undifferentiated arthritis. The
      JAMAR components discriminated well healthy subjects from JIA patients. All JAMAR
      components revealed satisfactory psychometric performances. In conclusion, the
      Omani Arabic version of the JAMAR is a valid tool for the assessment of children
      with JIA and is suitable for use both in routine clinical practice and clinical
      research.

PMID- 29637368
TI  - The Chilean Spanish version of the Juvenile Arthritis Multidimensional Assessment
      Report (JAMAR).
AB  - The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new
      parent/patient reported outcome measure that enables a thorough assessment of the
      disease status in children with juvenile idiopathic arthritis (JIA). We report
      the results of the cross-cultural adaptation and validation of the parent and
      patient versions of the JAMAR in the Chilean Spanish language. The reading
      comprehension of the questionnaire was tested in ten JIA parents and patients.
      Each participating centre was asked to collect demographic, clinical data and the
      JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6
      month period and to administer the JAMAR to 100 healthy children and their
      parents. The statistical validation phase explored descriptive statistics and the
      psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling
      effects, internal consistency, Cronbach's alpha, interscale correlations, and
      construct validity (convergent and discriminant validity). A total of 49 JIA
      patients (12.2% systemic, 24.5% oligoarticular, 22.5% RF-negative polyarthritis,
      40.8% other categories) and 70 healthy children, were enrolled. The JAMAR
      components discriminated well healthy subjects from JIA patients. All JAMAR
      components revealed good psychometric performances. In conclusion, the Chilean
      Spanish version of the JAMAR is a valid tool for the assessment of children with
      JIA and is suitable for use both in routine clinical practice and clinical
      research.

PMID- 29637369
TI  - The Russian version of the Juvenile Arthritis Multidimensional Assessment Report
      (JAMAR).
AB  - The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new
      parent/patient-reported outcome measure that enables a thorough assessment of the
      disease status in children with juvenile idiopathic arthritis (JIA). We report
      the results of the cross-cultural adaptation and validation of the parent and
      patient versions of the JAMAR in the Russian language. The reading comprehension
      of the questionnaire was tested in 10 JIA parents and patients. Each
      participating centre was asked to collect demographic, clinical data and the
      JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6
      month period and to administer the JAMAR to 100 healthy children and their
      parents. The statistical validation phase explored descriptive statistics and the
      psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling
      effects, internal consistency, Cronbach's alpha, interscale correlations, test
      retest reliability, and construct validity (convergent and discriminant
      validity). A total of 100 JIA patients (25% systemic, 19% oligoarticular, 38% RF
      negative polyarthritis, 18% other categories) and 198 healthy children, were
      enrolled in two centres. The JAMAR components discriminated healthy subjects from
      JIA patients. All JAMAR components revealed good psychometric performances. In
      conclusion, the Russian version of the JAMAR is a valid tool for the assessment
      of children with JIA and is suitable for use both in routine clinical practice
      and clinical research.

PMID- 29637370
TI  - The Paraguayan Spanish version of the Juvenile Arthritis Multidimensional
      Assessment Report (JAMAR).
AB  - The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new
      parent/patient reported outcome measure that enables a thorough assessment of the
      disease status in children with juvenile idiopathic arthritis (JIA). We report
      the results of the cross-cultural adaptation and validation of the parent and
      patient versions of the JAMAR in the Paraguayan Spanish language. The reading
      comprehension of the questionnaire was tested in 10 JIA parents and patients.
      Each participating centre was asked to collect demographic, clinical data and the
      JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6
      month period and to administer the JAMAR to 100 healthy children and their
      parents. The statistical validation phase explored descriptive statistics and the
      psychometric issues of the JAMAR: the 3 Likert assumptions, floor/ceiling
      effects, internal consistency, Cronbach's alpha, interscale correlations, and
      construct validity (convergent and discriminant validity). A total of 51 JIA
      patients (2% systemic, 27.4% oligoarticular, 37.2% RF negative polyarthritis,
      33.4% other categories) and 100 healthy children, were enrolled. The JAMAR
      components discriminated well healthy subjects from JIA patients. Notably, there
      was no significant difference between healthy subjects and their affected peers
      in the school-related problem variable. All JAMAR components revealed good
      psychometric performances. In conclusion, the Paraguayan Spanish version of the
      JAMAR is a valid tool for the assessment of children with JIA and is suitable for
      use both in routine clinical practice and clinical research.

PMID- 29637371
TI  - The Georgian version of the Juvenile Arthritis Multidimensional Assessment Report
      (JAMAR).
AB  - The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new
      parent/patient reported outcome measure that enables a thorough assessment of the
      disease status in children with juvenile idiopathic arthritis (JIA). We report
      the results of the cross-cultural adaptation and validation of the parent and
      patient versions of the JAMAR in the Georgian language. The reading comprehension
      of the questionnaire was tested in 10 JIA parents and patients. Each
      participating centre was asked to collect demographic, clinical data and the
      JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6
      month period and to administer the JAMAR to 100 healthy children and their
      parents. The statistical validation phase explored descriptive statistics and the
      psychometric issues of the JAMAR: the 3 Likert assumptions, floor/ceiling
      effects, internal consistency, Cronbach's alpha, interscale correlations, test
      retest reliability, and construct validity (convergent and discriminant
      validity). A total of 100 JIA patients (26% systemic, 57% oligoarticular, 16% RF
      negative polyarthritis, and 1% RF positive polyarthritis) and 100 healthy
      children, were enrolled at two paediatric rheumatology centre. Notably, none of
      the enrolled JIA patients is affected with psoriatic arthritis or with enthesitis
      related arthritis or with undifferentiated arthritis. The JAMAR components
      discriminated healthy subjects from JIA patients, except for the school-related
      problems variable. All JAMAR components revealed good psychometric performances.
      In conclusion, the Georgian version of the JAMAR is a valid tool for the
      assessment of children with JIA and is suitable for use both in routine clinical
      practice and clinical research.

PMID- 29637372
TI  - The Colombian Spanish version of the Juvenile Arthritis Multidimensional
      Assessment Report (JAMAR).
AB  - The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new
      parent/patient-reported outcome measure that enables a thorough assessment of the
      disease status in children with juvenile idiopathic arthritis (JIA). We report
      the results of the cross-cultural adaptation and validation of the parent and
      patient versions of the JAMAR in the Colombian Spanish language. The reading
      comprehension of the questionnaire was tested in ten JIA parents and patients.
      Each participating centre was asked to collect demographic, clinical data and the
      JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6
      month period and to administer the JAMAR to 100 healthy children and their
      parents. The statistical validation phase explored descriptive statistics and the
      psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling
      effects, internal consistency, Cronbach's alpha, interscale correlations, and
      construct validity (convergent and discriminant validity). A total of 22 JIA
      patients (9.1% systemic, 27.3% RF-negative polyarthritis, 36.4% enthesitis
      related arthritis, 27.2% other categories) were enrolled in the paediatric centre
      of Bogota. All JAMAR components revealed good psychometric performances. In
      conclusion, the Colombian Spanish version of the JAMAR is a valid tool for the
      assessment of children with JIA and is suitable for use both in routine clinical
      practice and clinical research.

PMID- 29637373
TI  - Preface.

PMID- 29637374
TI  - Clinical profile and outcome of children with scrub typhus from Chennai, South
      India.
AB  - : Scrub typhus is an acute febrile illness caused by Orientia tsutsugamushi. We
      prospectively studied the clinico-laboratory profile and outcome of 358 children
      aged 1 day to 18 years diagnosed with scrub typhus from Chennai, South India. All
      children (100%) had fever. Eschar was seen in 67%. All children were treated with
      oral doxycycline and those with complications were treated with intravenous
      chloramphenicol/azithromycin. Rapid defervescence (within 48 h) after initiation
      of doxycline was seen in 306 (85%) and 52 (14.5%) developed complications.
      Multivariate logistic regression analysis revealed that children who had an
      elevated aspartate amino transferase (> 120 IU/L) and the presence of
      thrombocytopenia (platelet count less than 1 lac cells/mm3) at admission had high
      risk of developing complications. The overall mortality rate in this series was
      0.8%. CONCLUSION: Our 4-year study highlights the clinico-laboratory profile of
      Scrub typhus in children from Chennai, South India. Early recognition and prompt
      treatment reduces the complication and mortality. What is Known: * Scrub typhus
      is endemic to tsutsugamushi triangle, a geographical triangle extending from
      northern Japan in the east to Pakistan and Afghanistan in the west and northern
      Australia in the south. * There is paucity of data regarding its clinico
      laboratory profile in neonates as well as its predictors of outcome. What is New:
      * Children who had an elevated AST and the presence of thrombocytopenia at
      admission had high risk of developing complications.

PMID- 29637376
TI  - History: Tribute to Ralph Lazarra, MD (August 14, 1934-January 16, 2018).

PMID- 29637375
TI  - Pain and quality of life of children and adolescents with osteogenesis imperfecta
      over a bisphosphonate treatment cycle.
AB  - : The objective was to describe the pain and quality of life among children and
      adolescents with any osteogenesis imperfecta (OI) type over one intravenous
      bisphosphonate treatment cycle from a child and parental perspective. A
      prospective, observational study was conducted, where children and adolescents
      evaluated their pain intensity, location, and quality, as well as quality of life
      before, 1 week after treatment, and 6 months later. Quality of life was also
      evaluated from the parental perspective at the same three time points. Thirty
      three child/parent dyads participated. The results showed that pain intensity on
      the 0-10 self-report scale after the Zoledronate infusion (median = 0, range = 0
      6) was not different from pre (median = 2, range = 0-10) and 6-months post-scores
      (median = 2, range = 0-8) (p = 0.170). Children and adolescents with OI reported
      experiencing pain mainly in the ankles and the anterior and posterior shoulders.
      They selected evaluative pain descriptors such as uncomfortable (n = 16, 48%) and
      annoying (n = 13, 39%). Children and adolescents' functioning and quality of life
      did not change significantly across the bisphosphonate treatment cycle (p =
      0.326), parents perceived an improvement immediately after the treatment compared
      to before (p = 0.016). CONCLUSION: Children and adolescents with OI experience
      mild, yet complex pain localized across several body areas. There is little
      fluctuation in the pain intensity and functioning of children with OI undergoing
      bisphosphonate treatment. What is Known: * Acute and chronic musculoskeletal pain
      remains a major issue in OI. * Pain has a negative impact on quality of life.
      What is New: * New and unpublished methods and findings describing the pain and
      quality of life of children and adolescents with OI over one intravenous
      bisphosphonate treatment cycle from a child- and parental-proxy perspective. *
      Children and adolescents with OI experience pain intensity that is mild, yet
      complex in quality and localized across several body areas.

PMID- 29637377
TI  - Rabbit model to simulate the residual conduction gaps after radiofrequency
      ablation on the anterior wall of left atrial appendage.
AB  - PURPOSE: Radiofrequency ablation (RFA) is widely used to treat patients with
      atrial fibrillation (AF), but its recurrence rate is still high mainly due to
      pulmonary vein reconnection and residual conduction gaps. We aim to establish a
      rabbit model to simulate the residual conduction gaps after ablation. METHODS:
      Sixty-nine adult New Zealand white rabbits were randomly assigned to six groups.
      RFA on the anterior wall of left atrial appendage (LAA) were performed with the
      ablation power from 6 to 21 W. The electrophysiological pacing and mapping
      technology was used to evaluate the bidirectional conduction of LAA. Histological
      study and fluorescence techniques were used to evaluate the effect of RFA and the
      accumulation of drug-loaded liposome on the loop ablation lesions of LAA.
      RESULTS: Typical loop ablation lesions of LAA could be observed in vivo and vitro
      of rabbit models. Histological evaluation revealed coagulative necrosis on the
      loop ablation lesions. Electrical conduction between inside and outside loop
      lesions recovered after 1 or 2 weeks after initial unidirectional conduction
      block. The recurrence rates were significantly different among six groups with
      varying ablation powers (p < 0.05). Compared with exit conduction block, entrance
      conduction block was significantly different at 5 min after ablation (p = 0.02).
      IR-775-loaded liposomes were accumulated on the loop ablation lesions at 48 h
      after RFA. CONCLUSIONS: RFA associated with electrophysiological pacing and
      mapping technology successfully established a novel rabbit model to simulate the
      residual conduction gaps after RFA.

PMID- 29637378
TI  - Pressure monitoring predicts pulmonary vein occlusion in cryoballoon ablation.
AB  - PURPOSE: Pulmonary venography is routinely used to confirm pulmonary vein (PV)
      occlusion during cryoballoon ablation. However, this technique is significantly
      limited by the risks associated with contrast media, such as renal injury and
      contrast allergy. We hypothesized that PV occlusion can be predicted by elevation
      of the balloon catheter tip pressure, avoiding the need for contrast media.
      METHODS: Forty-eight consecutive patients with paroxysmal atrial fibrillation who
      underwent PV isolation with the cryoballoon technique were enrolled. The balloon
      catheter tip pressure was measured in each PV before and after balloon inflation.
      RESULTS: We analyzed 200 applications of cryoballoon ablation in 185 PVs
      (excluding 3 common PVs and 1 extremely small right inferior PV) of 48 patients
      (age, 70 +/- 11 years; male, n = 28; mean left atrial diameter, 38 +/- 6 mm).
      Compared with patients with unsuccessful occlusion, patients with successful
      occlusion demonstrated a larger change in pressure after balloon inflation (6 +/-
      8 vs. 2 +/- 4 mmHg, P < 0.001), a lower minimum temperature (- 49 +/- 6 vs. - 40
      +/- 8  degrees C, P < 0.001), and a higher PV isolation rate (97 vs. 64%, P <
      0.001). The best cutoff value of a change in pressure for predicting PV occlusion
      was 4.5 mmHg, with a sensitivity of 67%, specificity of 83%, and predictive
      accuracy of 72%. CONCLUSION: Pressure monitoring is helpful to confirm PV
      occlusion during cryoballoon ablation.

PMID- 29637379
TI  - Bioconversion of Chitin to Bioactive Chitooligosaccharides: Amelioration and
      Coastal Pollution Reduction by Microbial Resources.
AB  - Chitin-metabolizing products are of high industrial relevance in current scenario
      due to their wide biological applications, relatively lower cost, greater
      abundance, and sustainable supply. Chitooligosaccharides have remarkably wide
      spectrum of applications in therapeutics such as antitumor agents,
      immunomodulators, drug delivery, gene therapy, wound dressings, as chitinase
      inhibitors to prevent malaria. Hypocholesterolemic and antimicrobial activities
      of chitooligosaccharides make them a molecule of choice for food industry, and
      their functional profile depends on the physicochemical characteristics.
      Recently, chitin-based nanomaterials are also gaining tremendous importance in
      biomedical and agricultural applications. Crystallinity and insolubility of
      chitin imposes a major hurdle in the way of polymer utilization. Chemical
      production processes are known to produce chitooligosaccharides with variable
      degree of polymerization and properties along with ecological concerns.
      Biological production routes mainly involve chitinases, chitosanases, and chitin
      binding proteins. Development of bio-catalytic production routes for chitin will
      not only enhance the production of commercially viable chitooligosaccharides with
      defined molecular properties but will also provide a means to combat marine
      pollution with value addition.

PMID- 29637380
TI  - Improving rice grain length through updating the GS3 locus of an elite variety
      Kongyu 131.
AB  - BACKGROUND: Traditional crop breeding has made significant achievement meet food
      needs worldwide. However, the way has some inevitable problems including time
      consuming, laborious, low predictability and reproducibility. In this study, we
      updated the GRAIN SIZE 3 (GS3) locus to improve the grain length of a major
      cultivate variety of Kongyu 131 at Heilongjiang Province, the northernmost region
      of China. High-resolution melting (HRM) analysis is used for single nucleotide
      polymorphism (SNP) genotyping. RESULTS: The improved line introgressed about 117
      kb segment including gs3 allele from donor GKBR by using five SNP markers
      designed within and without GS3 locus, and the background recovery ratio of the
      recurrent parent genome is about 99.55% that are detected by 219 SNP markers
      evenly distributed on the 12 chromosomes. The field trial indicates that grain
      length, 100-grain weight and total grain weight per plant of the improved line
      raised by 12.05%, 16.30% and 4.47%, respectively, compared with Kongyu 131.
      CONCLUSIONS: This result demonstrates that update the GS3 locus is a feasible and
      efficient and accurate way can be applied to improve grain size of rice.

PMID- 29637381
TI  - Inclusion of Pediococcus acidilactici as probiotic candidate in diets for beluga
      (Huso huso) modifies biochemical parameters and improves immune functions.
AB  - Administration of probiotic candidates in fish has generally been shown as a
      useful strategy to improve growth performance, survival, digestive enzyme
      activity, and gut microbiota. Unfortunately, the sero-immunological responses of
      different fish to different probiotic candidates are poorly understood. The
      present study assessed the effect of Pediococcus acidilactici as a probiotic on
      the biochemical and immunological parameters of beluga. Fish (248.32 +/- 10.21 g)
      were fed a control diet (without P. acidilactici( and three different doses of P.
      acidilactici-supplemented diets (107, 108, and 109 CFUg-1 diets) for 8 weeks. On
      week 8, blood and serum were sampled. Dose-dependent increase of immunological
      parameters (respiratory burst activity, lysozyme content, serum antibacterial
      activity, and total immunoglobulin) and biochemical parameters (total protein and
      albumin levels) was observed. However, alanine aminotransferase (ALT) and
      aspartate aminotransferase (AST) were significantly increased in the juvenile
      beluga fed by 109 CFUg-1 P. acidilactici-supplemented diet compared to the other
      groups. Based on the results of this evaluation, it is reasonable to conclude
      that the inclusion of P. acidilactici as probiotic in diets for juvenile beluga
      improves the sero-immunological parameters of the fish and should be considered
      by farmers as a strategy to improve fish health.

PMID- 29637382
TI  - Effects of CD100 promote wound healing in diabetic mice.
AB  - Diabetes is a condition that causes delayed wound healing and results in chronic
      wounds. CD100 has been reported to promote and induce potent and obvious
      angiogenesis both in vivo and in vitro studies, the absence of which are a main
      cause of the diabetic chronic wound. In the present study, we investigated the
      effects of application of soluble CD100 on wound healing in diabetic mice. Four 5
      mm full-thickness dermal wounds were made on each male db/db mouse. 12 mice from
      CD100 group were subcutaneously injected with 250 ng of CD100 (50 ul) per wound,
      in addition, 12 mice were injected with the same volume phosphate-balanced
      solution as the control. The animals were treated every other day until the
      wounds healed completely. Images were obtained to calculate the area ratio of the
      original area. HE and Masson's trichrome staining were used for histological
      examination. Collagen remodeling, angiogenesis and wound bed inflammation were
      evaluated by immunohistochemical staining and western blot. We demonstrated that
      CD100 had distinct functions during the wound healing process. Histological and
      western blotting analysis showed a more organized epithelium and dermis, more
      collagen fibers, higher angiogenesis and lower inflammation in the CD100 group
      than in the PBS group. These findings suggest that CD100 may accelerate wound
      healing in diabetic mice by promoting angiogenesis in the wound and by reducing
      the inflammatory response.

PMID- 29637383
TI  - Management of Interstitial Lung Disease in Patients With Myositis Specific
      Autoantibodies.
AB  - PURPOSE OF REVIEW: To review advances in the management of idiopathic
      inflammatory myopathy-associated interstitial lung disease (IIM-associated ILD)
      in the past 5 years, with highlights in myositis-specific antibody (MSA) groups.
      RECENT FINDINGS: With the recent advent of widespread MSA testing, the study of
      specific homogeneous autoantibody-based subgroups of IIM-associated ILD is now
      possible. The prevalence, severity, prognosis, and response to treatment are
      under study for these individual MSAs. Early evidence suggests that PL-7- and PL
      12-positive patients are more likely to have ILD and worse severity, compared to
      Jo-1 patients. Many medications have been efficacious for the treatment of IIM
      associated ILD, including calcineurin inhibitors, rituximab, and
      cyclophosphamide. We suggest vigilant screening and monitoring of ILD in IIM
      patients with focus on the potential side effects associated with therapy and
      thus advocate appropriate vaccination, PCP prophylaxis, and bone health
      protection. Many different agents are used to manage patients with ILD with no
      comparative effectiveness studies to guide the clinician. The possibility of
      using MSAs to help guide treatment decisions is an appealing, although unproven,
      focus of research. Unfortunately, the rarity of non-Jo-1 myositis-specific
      antibodies has precluded robust study of response to treatment and overall
      management. Ongoing clinical trials and working groups are coordinating efforts
      to provide evidence-based management.

PMID- 29637384
TI  - Stacked generalization: an introduction to super learning.
AB  - Stacked generalization is an ensemble method that allows researchers to combine
      several different prediction algorithms into one. Since its introduction in the
      early 1990s, the method has evolved several times into a host of methods among
      which is the "Super Learner". Super Learner uses V-fold cross-validation to build
      the optimal weighted combination of predictions from a library of candidate
      algorithms. Optimality is defined by a user-specified objective function, such as
      minimizing mean squared error or maximizing the area under the receiver operating
      characteristic curve. Although relatively simple in nature, use of Super Learner
      by epidemiologists has been hampered by limitations in understanding conceptual
      and technical details. We work step-by-step through two examples to illustrate
      concepts and address common concerns.

PMID- 29637385
TI  - Blood Pressure Goals in Acute Stroke-How Low Do You Go?
AB  - PURPOSE OF REVIEW: Elevations in systolic blood pressure (BP) greater than 140
      mmHg are reported in the majority (75%) of patients with acute ischemic stroke
      and in 80% of patients with acute intracerebral hemorrhages (ICH). This paper
      summarizes and updates the current knowledge regarding the proper management
      strategy for elevated BP in patients with acute stroke. Recent studies have
      generally showed a neutral effect of BP reduction on clinical outcomes among
      acute ischemic stroke patients. Thus, because of the lack of convincing evidence
      from clinical trials, aggressive BP reduction in patients presenting with acute
      ischemic stroke is currently not recommended. Although in patients treated with
      intravenous tissue plasminogen activator, guidelines are recommending BP <
      180/105 mmHg but currently, the optimal BP management after reperfusion therapy
      still remains unclear. In acute ICH, the evidence from randomized clinical trials
      supports the immediate BP lowering targeting systolic BP to 140 mmHg, which is
      now recommended by guidelines.

PMID- 29637386
TI  - Discordance of Self-report and Laboratory Measures of HIV Viral Load Among Young
      Men Who Have Sex with Men and Transgender Women in Chicago: Implications for
      Epidemiology, Care, and Prevention.
AB  - Suppressing HIV viral load through daily antiretroviral therapy (ART)
      substantially reduces the risk of HIV transmission, however, the potential
      population impact of treatment as prevention (TasP) is mitigated due to
      challenges with sustained care engagement and ART adherence. For an undetectable
      viral load (VL) to inform decision making about transmission risk, individuals
      must be able to accurately classify their VL as detectable or undetectable.
      Participants were 205 HIV-infected young men who have sex with men (YMSM) and
      transgender women (TGW) from a large cohort study in the Chicago area. Analyses
      examined correspondence among self-reported undetectable VL, study-specific VL,
      and most recent medical record VL. Among HIV-positive YMSM/TGW, 54% had an
      undetectable VL (< 200 copies/mL) via study-specific laboratory testing.
      Concordance between self-report and medical record VL values was 80% and between
      self-report and study-specific laboratory testing was 73%; 34% of participants
      with a detectable study-specific VL self-reported an undetectable VL at last
      medical visit, and another 28% reported not knowing their VL status. Periods of
      lapsed viral suppression between medical visits may represent a particular risk
      for the TasP strategy among YMSM/TGW. Strategies for frequent viral load
      monitoring, that are not burdensome to patients, may be necessary to optimize
      TasP.

PMID- 29637387
TI  - Characteristics of Out-of-Care Patients Who Required a Referral for Re-engagement
      Services by Public Health Bridge Counselors Following a Brief Clinic-Based
      Retention Intervention.
AB  - The NC-LINK Project initiated both clinic-based retention services and state
      public health bridge counselor-based (SBCs) re-engagement services to retain and
      re-engage people living with HIV infection (PLWH) in care. The goal of this
      project is to compare efforts between clinic-based retention and SBC re
      engagement services to determine whether patients are more or less likely to
      remain in HIV care services. Clinic appointment data were used to identify
      patients who were last seen more than 6-9 months prior. Patients either received
      clinic-based retention services only or were subsequently referred to the SBC re
      engagement intervention if the retention services were unsuccessful. The
      frequency of re-engagement in care (180 days) and HIV suppression (VLS, within 1
      year) was examined for patients in these two groups. The SBC group was less
      likely to have VLS at the visit prior to referral (adjusted OR 2.04, 95% CI 1.53,
      2.72). Patients who were referred to the SBC were less likely to re-engage in
      care within 180 days as compared to those who received clinic-based retention
      services only (adjusted OR 0.29, 95% CI 0.21, 0.41).

PMID- 29637388
TI  - Spare some internal limiting membrane for later: free ILM patch and neurosensory
      retina graft.
AB  - PURPOSE: Editorial to De Giacinto et al case report on free autologous
      neurosensory retina patch. METHODS: Literature review and experts' opinion
      RESULTS: In the present issue, De Giacinto et al describe a free autologous
      neurosensory retina patch to close a chronic macular hole. This new technique was
      made necessary by an extended internal limiting membrane peeling during the first
      surgery, that prevented grafting a patch of internal limiting membrane when the
      hole did not close. We hereby review pros and cons of patching a chronic macular
      hole with an internal limiting membrane patch, as well as the importance of not
      over-enlarging a peeling. DISCUSSION: Internal limiting membrane patch can be
      considered in chronic macular holes. It may not be an option in cases of over
      enlargement of a previous peel; free autologous neurosensory retina patch may be
      a valid alternative in such cases.

PMID- 29637389
TI  - Application and advantages of monoenergetic reconstruction images for the
      reduction of metallic artifacts using dual-energy CT in knee and hip prostheses.
AB  - OBJECTIVE: The study aimed to assess image quality when using dual-energy CT
      (DECT) to reduce metal artifacts in subjects with knee and hip prostheses.
      METHODS: Twenty-two knee and 10 hip prostheses were examined in 31 patients using
      a DECT protocol (tube voltages 100 and 140 kVp). Monoenergetic reconstructions
      were extrapolated at 64, 69, 88, 105, 110, 120, 140, 170, and 190 kilo-electron
      volts (keV) and the optimal energy was manually selected. The B60-140 and Fast DE
      reconstructions were made by CT. The image quality and diagnostic value were
      subjectively and objectively determined. Double-blind qualitative assessment was
      performed by two radiologists using a Likert scale. For quantitative analysis, a
      circular region of interest (ROI) was placed by a third radiologist within the
      most evident streak artifacts on every image. Another ROI was placed in
      surrounding tissues without artifacts as a reference. RESULTS: The inter-reader
      agreement for the qualitative assessment was nearly 100%. The best overall image
      quality (37.8% rated "excellent") was the Fast DE Siemens reconstruction,
      followed by B60-140 and Opt KeV (20.5 and 10.2% rated excellent). On the other
      hand, DECT images at 64, 69 and 88 keV had the worse scores. The number of
      artifacts was significantly different between monoenergetic images. Nevertheless,
      because of the high number of pairwise comparisons, no differences were found in
      the post hoc analysis except for a trend toward statistical significance when
      comparing the 170 and 64 keV doses. CONCLUSIONS: DECT with specific post
      processing may reduce metal artifacts and significantly enhance the image quality
      and diagnostic value when evaluating metallic implants.

PMID- 29637390
TI  - Understanding the Haemodynamics of Hypertension.
AB  - PURPOSE OF REVIEW: This article introduces the haemodynamic principles that
      underpin the pathophysiology of hypertension and introduces a rational
      physiological approach to appropriate pharmacologic treatment. RECENT FINDINGS:
      Outdated understanding of haemodynamics based on previous measurement systems can
      no longer be applied to our understanding of the circulation. We question the
      current view of hypertension as defined by a predominantly systolic blood
      pressure and introduce the concept of vasogenic, cardiogenic and mixed-origin
      hypertension. We postulate that failure to identify the individual's haemodynamic
      pattern may lead to the use of inappropriate medication, which in turn may be a
      major factor in patient non-compliance with therapeutic strategies. A population
      based approach to treatment of hypertension may lead to suboptimal functional
      dynamics in the individual patient. Finally, we question the validity of current
      guidelines and published evidence relating morbidity and mortality to the future
      treatment of hypertension. The importance of individual haemodynamic profiles may
      be pivotal in the understanding, diagnosis and treatment of hypertension if
      optimal control with minimal adverse effects is to be achieved. Research based on
      individual haemodynamic patterns is overdue.

PMID- 29637392
TI  - Prediction of Software Reliability using Bio Inspired Soft Computing Techniques.
AB  - A lot of models have been made for predicting software reliability. The
      reliability models are restricted to using particular types of methodologies and
      restricted number of parameters. There are a number of techniques and
      methodologies that may be used for reliability prediction. There is need to focus
      on parameters consideration while estimating reliability. The reliability of a
      system may increase or decreases depending on the selection of different
      parameters used. Thus there is need to identify factors that heavily affecting
      the reliability of the system. In present days, reusability is mostly used in the
      various area of research. Reusability is the basis of Component-Based System
      (CBS). The cost, time and human skill can be saved using Component-Based Software
      Engineering (CBSE) concepts. CBSE metrics may be used to assess those techniques
      which are more suitable for estimating system reliability. Soft computing is used
      for small as well as large-scale problems where it is difficult to find accurate
      results due to uncertainty or randomness. Several possibilities are available to
      apply soft computing techniques in medicine related problems. Clinical science of
      medicine using fuzzy-logic, neural network methodology significantly while basic
      science of medicine using neural-networks-genetic algorithm most frequently and
      preferably. There is unavoidable interest shown by medical scientists to use the
      various soft computing methodologies in genetics, physiology, radiology,
      cardiology and neurology discipline. CBSE boost users to reuse the past and
      existing software for making new products to provide quality with a saving of
      time, memory space, and money. This paper focused on assessment of commonly used
      soft computing technique like Genetic Algorithm (GA), Neural-Network (NN), Fuzzy
      Logic, Support Vector Machine (SVM), Ant Colony Optimization (ACO), Particle
      Swarm Optimization (PSO), and Artificial Bee Colony (ABC). This paper presents
      working of soft computing techniques and assessment of soft computing techniques
      to predict reliability. The parameter considered while estimating and prediction
      of reliability are also discussed. This study can be used in estimation and
      prediction of the reliability of various instruments used in the medical system,
      software engineering, computer engineering and mechanical engineering also. These
      concepts can be applied to both software and hardware, to predict the reliability
      using CBSE.

PMID- 29637391
TI  - Change in functioning outcomes as a predictor of the course of depression: a 12
      month longitudinal study.
AB  - PURPOSE: Functioning is a necessary diagnostic criterion for depression, and thus
      routinely assessed in depressive patients. While it is highly informative of
      disorder severity, its change has not been tested for prognostic purposes. Our
      study aimed to analyze to what extent early functioning changes predict
      depression in the mid-term. METHODS: Longitudinal study (four occasions:
      baseline, 1, 3, and 12 months) of 243 patients with depressive symptomatology at
      three different services (primary care, outpatients, and hospital). Functioning
      was assessed on the first three occasions using the Global Assessment of
      Functioning (GAF), the WHODAS-2.0, and a self-reported functioning (SRF) rating
      scale. Growth mixture modeling of initial assessments served to estimate
      individual person-change parameters of each outcome. Person-growth parameters
      were used as predictors of major depressive episode at 12 months in a logistic
      regression model, adjusted by sex, age, healthcare level, and depression clinical
      status at third month. Predictive accuracy of all measures was assessed with area
      under the receiver operating curve (AUC). RESULTS: Of the 179 patients who
      completed all assessments, 58% had an active depression episode at baseline and
      20% at 12 months (64% non-recoveries and 36% new onsets). Individual trends of
      change in functioning significantly predicted patient depression status a year
      later (AUCWHODAS = 0.76; AUCGAF = 0.92; AUCSRF = 0.93). CONCLUSIONS: Longitudinal
      modeling of functioning was highly predictive of patients' clinical status after
      1 year. Although clinical and patient-reported assessment had high prognostic
      value, the use of very simple patient-reported outcome measures could improve
      case management outside specialized psychiatric services.

PMID- 29637393
TI  - Clinical outcomes with biventricular versus right ventricular pacing in patients
      with atrioventricular conduction defects.
AB  - There have been increasing concerns about the unexpected effects of right
      ventricular (RV) pacing. We aimed to systematically evaluate the effect of
      biventricular (BiV) versus RV pacing on clinical events in patients with impaired
      AV conduction. We searched PubMed, EMBASE, and Cochrane Library for studies
      comparing BiV pacing with RV pacing in patients with AV block, through April
      2017. We selected randomized controlled trials (RCTs) reporting data on
      mortality, hospitalization for heart failure (HF), and/or 6-min walk distance
      (6MWD). A total of 12 RCTs were finally included. Pooled analysis suggested that
      BiV pacing was associated with a significantly reduced all-cause mortality in
      contrast to RV pacing (risk ratio (RR) = 0.77, 95% confidence interval (CI) 0.62
      to 0.95, I2 = 9.6%). BiV pacing, compared with RV pacing, significantly reduced
      the rate of HF hospitalization (RR = 0.74, 95% CI 0.59 to 0.93, I2 = 10.1%).
      Sensitivity analyses by excluding studies with AV nodal ablation showed that BiV
      pacing still had a lower mortality and non-significant reduced HF
      hospitalization. Patients in BiV and RV pacing mode had a similar 6WMD at follow
      up (mean difference = 4.99 m, 95% CI - 11.34 to 21.33 m, I2 = 0%). Meta
      regression analysis showed that the effect size of all-cause mortality or HF
      hospitalization was not significantly associated with mean LVEF value at
      baseline. In patients with impaired AV conduction that need frequent ventricular
      pacing, BiV pacing was associated with reduced mortality and hospitalization for
      HF, compared with traditional RV pacing mode.

PMID- 29637394
TI  - Gallaecimonas mangrovi sp. nov., a novel bacterium isolated from mangrove
      sediment.
AB  - A Gram-stain negative, rod-shaped, non-motile, strictly aerobic bacterium HK-28T
      was isolated from a mangrove sediment sample in Haikou city, Hainan Province,
      China. Strain HK-28T was able to grow at 10-45  degrees C (optimum 25-30  degrees
      C), pH 5.0-8.5 (optimum 6.0-7.0) and 0.5-12.0% (w/v) NaCl (optimum 1.0-3.0%,
      w/v). The major cellular fatty acids were C16:0, Summed Feature 8 (C18:1 omega7c
      and/or C18:1 omega6c), Summed Feature 3 (C16:1 omega7c and/or C16:1 omega6c),
      C17:0, C12:0 3-OH and C17:1omega8c. Ubiquinone-8 (Q-8) was the predominant
      respiratory quinone. The polar lipids consisted of diphosphatidylglycerol,
      phosphatidylglycerol, phosphatidylethanolamine, two unidentified
      aminophospholipids, four unidentified phospholipids, two unidentified glycolipid,
      an unidentified glycophospholipid, an unidentified aminolipid and an unidentified
      lipid. The DNA G+C content was 50.2 mol%. Accoroding to 16S rRNA gene sequence
      similarities, strain HK-28T shared 97.1 and 96.7% sequence similarities to the
      validly named species Gallaecimonas xiamenensis MCCC 1A01354T and Gallaecimonas
      pentaromativorans MCCC 1A06435T, respectively, and shared lower sequence
      similarities (< 92.0%) to all other genera. Phylogenetic analysis showed strain
      HK-28T was clustered with G. pentaromativorans MCCC 1A06435T and G. xiamenensis
      MCCC 1A01354T. Strain HK-28T showed low DNA-DNA relatedness with G. xiamenensis
      MCCC 1A01354T (28.3 +/- 1.5%) and G. pentaromativorans MCCC 1A06435T (25.2 +/-
      2.4%). On the basis of phenotypic, chemotaxonomic and genotypic characteristics,
      strain HK-28T is considered to represent a novel species in the genus
      Gallaecimonas, for which the name Gallaecimonas mangrovi sp. nov. is proposed.
      The type strain is HK-28T (= KCTC 62177T = MCCC 1K03441).

PMID- 29637395
TI  - The Effect of Pancreas Islet-Releasing Factors on the Direction of Embryonic Stem
      Cells Towards Pdx1 Expressing Cells.
AB  - Diabetes mellitus, which is the result of autoimmune destruction of the insulin
      producing beta cells, occurs by loss of insulin-secreting capacity. The
      insufficient source of insulin-producing cells (IPCs) is the major obstacle for
      using transplantation as diabetes treatment method. The present study suggests a
      method to form islet-like clusters of IPCs derived from mouse embryonic stem
      cells (mESCs). This protocol consists of several steps. Before starting this
      protocol, embryoid bodies (EBs) should be cultured in suspension in conditioned
      medium of isolated mouse pancreatic islet in combination with activing A to be
      induced. Then differentiated mESCs were replaced with dishes supplemented with
      basic fibroblast growth factor (bFGF). Next, bFGF was withdrawn, and cyclopamine
      and noggin were added. Then the cells were treated with B27, nicotinamide, and
      islet-conditioned medium for maturation. mESCs, as the control group, were
      cultured without any treatment. An enhanced expression of pancreatic-specific
      genes was detected by qRT-PCR and immunofluorescence in the differentiated mESCs.
      The differentiated mESCsco express other markers of pancreatic islet cells as
      well as insulin. This method exhibited higher insulin generation and further
      improvement in IPCs protocol that may result in an unlimited source of ES cells
      suitable for transplantation. The results indicated that conditioned medium, just
      as critical components of the stem cell niche associated with other factors, had
      high potential to differentiate mESCs into IPCs.

PMID- 29637396
TI  - Co-addition Strategy for Enhancement of Chaetominine from Submerged Fermentation
      of Aspergillus fumigatus CY018.
AB  - Chaetominine (CHA), a novel framework tripeptide alkaloid, imparts an attractive
      cytotoxic against the human leukemia cell line K562, which is produced by
      Aspergillus fumigatus CY018. However, its pharmacological research is restricted
      by low yields in submerged culture, which needs to be resolved immediately by
      biotechnology. In this work, a co-addition strategy was applied to promote CHA
      production based on related inhibitors' addition and precursors' addition,
      inspired by the biosynthetic pathway analysis of CHA. CHA production reached
      53.87 mg/L by addition of 10 mM shikimate, 10 mM anthranilate, 20 mM tryptophan,
      and 10 mM alanine in shake flask. Compared to the control without addition of
      precursors, the activity of 3-deoxy-arabino-heptulosonate-7-phospahte (DAHP)
      synthase was significantly improved and the transcription levels of critical
      genes in shikimate pathway were up-regulated responded to the co-addition of
      precursors. The improvement of CHA production by co-addition of precursors was
      also successfully reproduced in the lab-scale bioreactor (5-L) system, in which
      CHA production reached 46.10 mg/L. This work demonstrated that precursors' co
      addition was an effective strategy for increasing CHA production, and the
      information obtained might be useful to the further improvement of CHA on a large
      scale.

PMID- 29637397
TI  - Author Correction: The Inhibitory Effect of Mesenchymal Stem Cells with rAd-NK4
      on Liver Cancer.
AB  - The original version of this article unfortunately contained a mistake in the
      image of Figure 7.

PMID- 29637399
TI  - Identifying risk factors associated with acquiring measles in an outbreak among
      age-appropriately vaccinated school children: a cohort analysis.
AB  - BACKGROUND: A measles outbreak occurred in age-appropriately vaccinated children
      in a school in a town in the South East of Ireland in September-November 2013.
      AIMS: The purpose of this study was to investigate the risk factors associated
      with catching measles during the outbreak. METHODS: Ninety-five children (4-5
      years) in three classes, in the first year of primary school, were included in
      the study. Immunisation records on the South East Child Health Information System
      for first Measles Mumps and Rubella (MMR) vaccine for the 95 children were
      reviewed. Data collected included age at MMR, date of administration of MMR, MMR
      brand and batch number, and the General Practice at which MMR was administered.
      The risk factors analysed included age at vaccination, time of vaccination, class
      and the GP practice where MMR was administered. Statistical analysis was
      performed using Epi info 7 and SPSS v24. RESULTS: Thirteen children in the cohort
      developed measles during the outbreak. All children in the cohort were age
      appropriately vaccinated, with one dose of MMR vaccine. Analysis demonstrated
      statistically significant differences in the relative risk of developing measles
      according to the class a child was in, and the General Practice at which they
      were vaccinated. CONCLUSIONS: The reason for intense measles activity in one
      class was not established. Although a concurrent investigation into cold chain
      and vaccine stock management did not identify a cause for the high relative risk
      of measles in children vaccinated, recommendations were made for improving cold
      chain and vaccine stock management in General Practices.

PMID- 29637398
TI  - Patterns and trends in lead (Pb) concentrations in bald eagle (Haliaeetus
      leucocephalus) nestlings from the western Great Lakes region.
AB  - Most studies examining bald eagle (Haliaeetus leucocephalus) exposure to lead
      (Pb) have focused on adults that ingested spent Pb ammunition during the fall
      hunting season, often at clinical or lethal levels. We sampled live bald eagle
      nestlings along waterbodies to quantify Pb concentrations in 3 national park
      units and 2 nearby study areas in the western Great Lakes region. We collected
      367 bald eagle nestling feather samples over 8 years during spring 2006-2015 and
      188 whole blood samples over 4 years during spring 2010-2015. We used Tobit
      regression models to quantify relationships between Pb concentrations in nestling
      feathers and blood using study area, year, and nestling attributes as covariates.
      Pb in nestling feather samples decreased from 2006 to 2015, but there was no
      trend for Pb in blood samples. Pb concentrations in nestling feather and blood
      samples were significantly higher in study areas located closer to and within
      urban areas. Pb in feather and blood samples from the same nestling was
      positively correlated. Pb in feathers increased with nestling age, but this
      relationship was not observed for blood. Our results reflect how Pb accumulates
      in tissues as nestlings grow, with Pb in feathers and blood indexing exposure
      during feather development and before sampling, respectively. Some nestlings had
      Pb concentrations in blood that suggested a greater risk to sublethal effects
      from Pb exposure. Our data provides baselines for Pb concentrations in feathers
      and blood of nestling bald eagles from a variety of waterbody types spanning
      remote, lightly populated, and human-dominated landscapes.

PMID- 29637400
TI  - Design of in situ porcine closed-circuit system for assessing blood-contacting
      biomaterials.
AB  - The overall pre-clinical process of determining the blood compatibility of any
      medical device involves several stages. Although the primary purpose is to
      protect the patients, laboratory testing has been over-utilized for many years
      with a huge number of unnecessary animal tests being done routinely. Recently,
      the elimination of needless testing has become important in controlling the cost
      of healthcare and in addressing many issues related to the ethics of animal
      research. With this in mind, we designed a new in situ porcine closed-circuit
      system to study the complex interplay between platelets, coagulation proteins,
      and other cellular elements in pigs. We proved that this system can be
      implemented in blood compatibility testing and minimize the number of animals
      used in the experiments.

PMID- 29637402
TI  - Atypically presenting kaposiform hemangioendothelioma of the knee: ultrasound
      findings.
AB  - Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor of early childhood
      and infancy. Kasabach-Merritt phenomenon, a common complication of KHE, is
      characterized by life-threatening thrombocytopenia, hemolytic anemia, and
      consumption coagulopathy. There may be atypical cases that do not present with
      Kasabach-Merritt phenomenon and do have atypical imaging findings. Knowledge of
      atypical imaging features may assist radiologists in identifying KHE. In this
      report, we present a 4-year-old case of KHE with atypical ultrasound findings.

PMID- 29637401
TI  - PET Imaging Reveals Brain Metabolic Changes in Adolescent Rats Following Chronic
      Escalating Morphine Administration.
AB  - PURPOSE: Non-medical use of prescription opioids, especially among adolescents,
      has been substantially increased in recent years. However, the neuromechanism
      remains largely unexplored. In the present study, we aimed to investigate the
      brain metabolic changes in adolescent rats following chronic escalating morphine
      administration using positron emission tomography (PET). PROCEDURES: 2-Deoxy-2
      [18F]Fluoro-D-glucose ([18F]FDG) microPET imaging was performed, and statistical
      parametric mapping (SPM) was used for image analysis. Glucose transporter 3 (Glut
      3), dopamine D2 receptor (D2R), and MMU-opioid receptor (MU-OR) were used for
      immunostaining analysis. RESULTS: Cerebral glucose metabolism was increased in
      the corpus callosum (CC) and right retrosplenial dysgranular cortex (rRSD), while
      it was decreased in the right ventral pallidum (rVP). The expressions of Glut-3,
      D2R, and MU-OR were increased in CC and rRSD, while they were decreased in rVP.
      Furthermore, glucose metabolism and Glut-3 expression were positively correlated
      with the expressions of D2R or MU-OR in CC, rRSD, and rVP. CONCLUSIONS: [18F]FDG
      microPET brain imaging study in combination with immunohistological investigation
      revealed that CC, rRSD, and rVP were specifically involved in opioid dependence
      in adolescents. Our findings provided valuable insights into the neuromechanism
      of adolescent addiction of prescription opioids and might have important
      implications for the development of prevention and intervention approaches.

PMID- 29637404
TI  - Long-acting olanzapine injection during pregnancy and breastfeeding: a case
      report.
AB  - We present one case of a woman treated with the intramuscular depot formulation
      of the atypical antipsychotic, olanzapine pamoate (ZypAdhera(r)), during
      pregnancy and breastfeeding. Data on olanzapine distribution in breast milk as
      well as on plasma concentration in the nursed infant are provided. The present
      case report demonstrates that olanzapine was excreted in the breast milk, but the
      breast-fed infant had very low olanzapine concentrations, which did not result in
      any adverse effects.

PMID- 29637403
TI  - Accurate Diabetes Risk Stratification Using Machine Learning: Role of Missing
      Value and Outliers.
AB  - Diabetes mellitus is a group of metabolic diseases in which blood sugar levels
      are too high. About 8.8% of the world was diabetic in 2017. It is projected that
      this will reach nearly 10% by 2045. The major challenge is that when machine
      learning-based classifiers are applied to such data sets for risk stratification,
      leads to lower performance. Thus, our objective is to develop an optimized and
      robust machine learning (ML) system under the assumption that missing values or
      outliers if replaced by a median configuration will yield higher risk
      stratification accuracy. This ML-based risk stratification is designed, optimized
      and evaluated, where: (i) the features are extracted and optimized from the six
      feature selection techniques (random forest, logistic regression, mutual
      information, principal component analysis, analysis of variance, and Fisher
      discriminant ratio) and combined with ten different types of classifiers (linear
      discriminant analysis, quadratic discriminant analysis, naive Bayes, Gaussian
      process classification, support vector machine, artificial neural network,
      Adaboost, logistic regression, decision tree, and random forest) under the
      hypothesis that both missing values and outliers when replaced by computed
      medians will improve the risk stratification accuracy. Pima Indian diabetic
      dataset (768 patients: 268 diabetic and 500 controls) was used. Our results
      demonstrate that on replacing the missing values and outliers by group median and
      median values, respectively and further using the combination of random forest
      feature selection and random forest classification technique yields an accuracy,
      sensitivity, specificity, positive predictive value, negative predictive value
      and area under the curve as: 92.26%, 95.96%, 79.72%, 91.14%, 91.20%, and 0.93,
      respectively. This is an improvement of 10% over previously developed techniques
      published in literature. The system was validated for its stability and
      reliability. RF-based model showed the best performance when outliers are
      replaced by median values.

PMID- 29637405
TI  - Is a driver's license age waiver worth a teen's life?
AB  - BACKGROUND: Motor vehicle crashes are the leading cause of death for teens 14-19
      years of age, with younger teen drivers at higher risk than older teens.
      Graduated driver licensing has been proven to reduce teen driver-related motor
      vehicle crashes and fatalities. Arkansas allows parents to request age waivers,
      which allow a teen to obtain a license for independent driving before the
      sixteenth birthday. The objectives of this study were to: (1) determine the
      prevalence of age waivers issued in Arkansas and (2) determine motor vehicle
      crash risks associated with 14 and 15 year old drivers. METHODS: This is a brief
      report on an informative query exploring risk factors related to age waivers.
      Publicly available databases were utilized for across state comparisons. The Web
      based Injury Statistics Query and Reporting Systems (WISQARS) was utilized to
      calculate motor vehicle crash crude death rates. National Highway Traffic Safety
      Administration data were utilized to identify seat belt use rates. The Fatal
      Analysis Reporting System (FARS) was utilized to identify crash fatality risks
      for 14 and 15 year old drivers in Arkansas (N = 24). Age waiver data were
      obtained from the Arkansas Driver Control Administration. De-identified data on
      fatal crashes and rates of age waiver issuance in Arkansas for 14 and 15 year
      olds from 2004 through 2016 were calculated. RESULTS: We reviewed crash data for
      14 and 15 year old drivers in Arkansas between 2004 and 2014 to determine
      fatality risks. Thirty-one out of seventy-five counties in Arkansas were above
      the state age waiver issuance rate of 30.4 per 1000 14 to 15 year old teens.
      Among the four states that had similar age waivers for 14 to 15 year olds,
      Arkansas had the highest motor vehicle death rate of 10.2 per 100,000 young teens
      and the lowest seat belt use rate at 73%. CONCLUSIONS: Arkansas had the highest
      reported teen crash fatality rates among 4 states with age waivers. The volume of
      age waivers issued in Arkansas is concerning. Further research is needed to
      understand parental motivation when asking for age waivers and their level of
      awareness of the risks involved.

PMID- 29637407
TI  - Cardiac output-based fluid optimization for kidney transplant recipients: a proof
      of-concept trial.
AB  - PURPOSE: Intravenous fluid management for deceased donor kidney transplantation
      is an important, modifiable risk factor for delayed graft function (DGF). The
      primary objective of this study was to determine if goal-directed fluid therapy
      using esophageal Doppler monitoring (EDM) to optimize stroke volume (SV) would
      alter the amount of fluid given. METHODS: This randomized, proof-of-concept trial
      enrolled 50 deceased donor renal transplant recipients. Data collected included
      patient characteristics, fluid administration, hemodynamics, and complications.
      The EDM was used to optimize SV in the EDM group. In the control group, fluid
      management followed the current standard of practice. The groups were compared
      for the primary outcome of total intraoperative fluid administered. RESULTS:
      There was no difference in the mean (standard deviation) volume of intraoperative
      fluid administered to the 24 control and 26 EDM patients [2,307 (750) mL vs 2,675
      (842) mL, respectively; mean difference, 368 mL; 95% confidence interval (CI), -
      87 to + 823; P = 0.11]. The incidence of complications in the control and EDM
      groups was similar (15/24 vs 17/26, respectively; P = 0.99), as was the incidence
      of delayed graft failure (8/24 vs 11/26, respectively; P = 0.36). CONCLUSIONS:
      Goal-directed fluid therapy did not alter the volume of fluid administered or the
      incidence of complications. This proof-of-concept trial provides needed data for
      conducting a larger trial to determine the influence of fluid therapy on the
      incidence in DGF in deceased donor kidney transplantation. TRIAL REGISTRATION:
      www.clinicaltrials.gov (NCT02512731). Registered 31 July 2015.

PMID- 29637408
TI  - Red Blood Cell and Serum Magnesium Levels Among Children and Adolescents With
      Sickle Cell Anemia.
AB  - Patients with sickle cell anemia (SCA) can acquire many biochemical
      abnormalities, including altered magnesium levels. However, the roles of
      magnesium in the pathogenesis and management of SCA need to be determined. The
      aim of this work was to evaluate magnesium levels among pediatric patients with
      SCA in Basra, Iraq. The study employed a case-control design and examined 87
      patients with SCA (3-15 years old) who had attended the Basra Center for
      Hereditary Blood Diseases while in a steady state and 90 apparently healthy
      control subjects. Complete blood count, red blood cell (RBC), and serum
      magnesium, calcium, potassium, sodium, zinc, and copper levels were measured in
      all subjects. The results revealed significantly lower RBC and serum magnesium
      levels among the patients with SCA (3.62 +/- 0.42 and 1.35 +/- 0.19 mg/dL,
      respectively) than those among the control subjects (4.47 +/- 0.55 and 1.87 +/-
      0.27 mg/dL, respectively). In addition, compared to the control subjects, the
      patients with SCA had significantly lower serum levels of potassium, sodium, and
      zinc; significantly higher serum levels of copper; and significantly higher Ca/Mg
      and Na/Mg ratios. Among the SCA patients, the RBC magnesium level was
      significantly negatively associated with the frequencies of vaso-occlusive crises
      (r = - 0.423, P < 0.001) and disease-related hospitalization (r = - 0.225, P <
      0.05). To conclude, the RBC magnesium level, but not the serum magnesium level,
      is significantly associated with vaso-occlusive crises and hospitalization.
      Therefore, screening and management of low RBC magnesium levels in SCA patients
      are required.

PMID- 29637406
TI  - Innovative Research Design to Meet the Challenges of Clinical Trials for Juvenile
      Dermatomyositis.
AB  - PURPOSE OF REVIEW: This paper aims to provide a summary of the recent therapeutic
      advances and the latest research on outcome measures for clinical trials in
      juvenile dermatomyositis (JDM). RECENT FINDINGS: Recent randomized controlled
      trials (RCTs) have demonstrated the superiority of the combination of prednisone
      with methotrexate over other conventional therapies and the potential
      effectiveness of rituximab in refractory cases. A multinational project has led
      to develop new criteria for the definition of minimal, moderate, and major
      improvement in future JDM clinical trials. This effort has been paralleled by the
      establishment of criteria for clinically inactive disease. The validation of the
      first composite disease activity score for JDM is in progress. The new outcome
      measures will increase the reliability of assessment of clinical response in JDM
      clinical trials and foster future multinational RCTs aimed to investigate novel
      treatment strategies for refractory forms of JDM.

PMID- 29637409
TI  - Cycle length identifies obstructive sleep apnea and central sleep apnea in heart
      failure with reduced ejection fraction.
AB  - AIM: To clarify whether unmasking of central sleep apnea during continuous
      positive airway pressure (CPAP) initiation can be identified from initial
      diagnostic polysomnography (PSG) in patients with heart failure with reduced
      ejection fraction (HFREF) and obstructive sleep apnea (OSA) MATERIALS AND
      METHODS: Forty-three consecutive patients with obstructive sleep apnea and
      central sleep apnea (OSA/CSA) in HFREF were matched with 43 HFREF patients with
      OSA and successful CPAP initiation. Obstructive apneas during diagnostic PSG were
      then analyzed for cycle length (CL), ventilation length (VL), apnea length (AL),
      time to peak ventilation (TTPV), and circulatory delay (CD). We calculated duty
      ratio (DR) as the ratio of VL/CL and mathematic loop gain (LG). RESULTS: While AL
      was similar, CL, VL, TTPV, CD, and DR was significantly longer in patients with
      OSA/CSA compared to those with OSA, and LG was significantly higher. Receiver
      operator curves identified optimal cutoff values of 50.2 s for CL (area under the
      curve (AUC) 0.85, 29.2 s for VL (AUC 0.92), 11.5 s for TTPV (AUC 0.82), 26.4 s
      for CD (AUC 0.79), and 3.96 (AUC 0.78)) respectively for LG to identify OSA/CSA.
      CONCLUSION: OSA/CSA in HFREF can be identified by longer CL, VL, TTPV, and CD
      from obstructive events in initial diagnostic PSG. The underlying mechanisms seem
      to be the presence of an increased LG.

PMID- 29637410
TI  - Does Robotic Roux-en-Y Gastric Bypass Provide Outcome Advantages over Standard
      Laparoscopic Approaches?
AB  - OBJECTIVE: The aim was to compare clinical outcomes of patients treated with
      totally robotic Roux-en-Y gastric bypass (TRRYGB) with those treated with the
      different laparoscopic Roux-en-Y gastric bypass (LRYGB) techniques. The clinical
      benefit of the robotic approach to bariatric surgery compared to the standard
      laparoscopic approach is unclear. There are no studies directly comparing
      outcomes of TRRYGB with different LRYGB techniques. METHODS: Outcomes of 578
      obese patients who underwent RYGB between 2011 and 2014 at an academic center
      were assessed. Multivariable analysis and propensity matching were used for
      comparing TRRYGB to different LRYGB techniques, including 21-mm EEA circular
      stapled gastrojejunal anastomosis (GJA, LRYGB-21CS), linear-stapled GJA (LRYGB
      LS), and hand-sewn GJA (LRYGB-HS). RESULTS: The TRRYGB technique required a
      longer mean operative time compared to the other groups, respectively 204 +/- 46
      vs. 139 +/- 30 min (LRYGB-21CS), 206 +/- 37 vs. 158 +/- 30 min (LRYGB-LS), and
      210 +/- 36 vs. 167 +/- 30 min (LRYGB-HS). TRRYGB experienced a lower stricture
      rate (2 vs. 17%, P = 0.003), shorter hospital stay (2.6 +/- 1.2 vs. 4.3 +/- 5.5
      days, P = 0.008), and lower readmission rate (12 vs. 28%, P = 0.009). No
      significant differences in outcomes were observed when comparing RRYGB to LRYGB
      LS or LRYGB-HS. CONCLUSIONS: TRRYGB increases operative time compared to all
      LRYGB techniques. TRRYGB was superior to LRYGB-21CS in terms of significantly
      shorter hospital stay, lower readmission rate, and less frequent GJA stricture
      formation. TRRYGB provides no clinical advantages over the LRYGB-LS and LRYGB-HS
      techniques.

PMID- 29637411
TI  - The Correlation Between Aqueous Humor Flow and IOP Before and After Trabectome:
      Developing a Grading System to Quantify Flow.
AB  - INTRODUCTION: To develop a grading system that provides objective quantification
      of flow through the conventional aqueous humor outflow (AHO) system. The
      technique gives clinicians an additional assessment option in the evaluation of
      glaucoma treatment approaches. METHODS: This was a retrospective observational
      study. This study evaluated the eyes of all primary open-angle glaucoma patients
      who underwent a Trabectome (NeoMedix Corp., Tustin, CA, USA) procedure with or
      without cataract surgery in the interval between April and September 2016 (n =
      73). The nasal hemisphere was divided into three regions. Utilizing a four-level
      grading system designed for this study, an aqueous humor outflow grade (G0-G3)
      was assigned to each region using a video taken during examinations. The
      individual grade levels of the three regions were combined to get a composite AHO
      score. The correlation between the composite AHO score and intraocular pressure
      (IOP) was then analyzed. Additionally, the speed of red blood cell (RBC) clusters
      in the episcleral veins (ESV) was calculated when made possible by the existence
      of pulsatile flow. RESULTS: At 3 months following the Trabectome procedure,
      average IOP decreased from 26 to 15 mmHg. Assessment of the relationship between
      AHO grade and IOP demonstrated that a high composite AHO score was correlated
      with lowered IOP (Tukey-Kramer method p < 0.05). Additionally, it was found that
      if one of the three regions had an AHO grade of >= G2, an IOP of < 20 mmHg could
      be predicted. (Fischer's exact test p < 0.0001). Calculated speed was as follows:
      at G1, the speed was 0.68 +/- 0.26 mm/s (n = 7), at G2, the speed was 1.8 +/-
      0.84 mm/s (n = 5), and at G3, the speed was 6.8 +/- 3.3 mm/s (n = 6). CONCLUSION:
      There was a significant correlation between an increase in the composite AHO
      score and a decrease in IOP. Additionally, the speed of RBC clusters as they
      traveled through the ESVs remained consistent for each of the grades, and the
      span of the speeds from lower to higher grades represented a significant range.
      These findings suggest that the grading system is a reliable measure of AHO.
      TRIAL REGISTRATION IDENTIFIER: UMIN 000031745.

PMID- 29637412
TI  - Media and Its Influence on Obesity.
AB  - PURPOSE OF REVIEW: To review how the media frames obesity and the effect it has
      upon on public perceptions. RECENT FINDINGS: The scientific and public health
      understanding of obesity increasingly points away from individual behaviors and
      toward medical and community factors, but diffusion of this knowledge is slow.
      Growing awareness of the importance of body positivity is driving attention to
      the harms of weight bias and fat shaming. Health science reporting related to
      obesity, nutrition, and physical activity tends to perpetuate myths and
      misunderstandings. Moving forward, greater attention to accurate messages about
      obesity and evidence-based interventions will be essential for progress to reduce
      suffering and the impact on public health from this chronic disease.

PMID- 29637413
TI  - Intestinal and Gastric Origins for Diabetes Resolution After Bariatric Surgery.
AB  - PURPOSE OF REVIEW: This paper will review the intestinal and gastric origins for
      diabetes resolution after bariatric surgery. RECENT FINDINGS: In addition to the
      known metabolic effects of changes in the gut hormonal milieu, more recent
      studies investigating the role of the microbiome and bile acids and changes in
      nutrient sensing mechanisms have been shown to have glycemic effects in human and
      animal models. Independent of weight loss, there are multiple mechanisms that may
      lead to amelioration or resolution of diabetes following bariatric surgery. There
      is abundant evidence pointing to changes in gut hormones, bile acids, gut
      microbiome, and intestinal nutrient sensing; more research is needed to clearly
      delineate their role in regulating energy and glucose homeostasis after bariatric
      surgery.

PMID- 29637415
TI  - Clinical and Molecular Features of Thiazide-Induced Hyponatremia.
AB  - PURPOSE OF REVIEW: Hypertension affects more than 30% of the world's adult
      population and thiazide (and thiazide-like) diuretics are amongst the most widely
      used, effective, and least costly treatments available, with all-cause mortality
      benefits equivalent to angiotensin-converting enzyme inhibitors or calcium
      channel antagonists. A minority of patients develop thiazide-induced hyponatremia
      (TIH) and this is largely unpredictable at the point of thiazide prescription. In
      some cases, TIH can cause debilitating symptoms and require hospital admission.
      Although TIH affects only a minority of patients exposed to thiazides, the high
      prevalence of hypertension leads to TIH being the most common cause of drug
      induced hyponatremia requiring hospital admission in the UK. This review examines
      current clinical and scientific understanding of TIH. Consideration is given to
      demographic associations, limitations of current electrolyte monitoring regimens,
      clinical presentation, the phenotype evident on routine clinical blood and urine
      tests as well as more extensive analyses of blood and urine in research settings,
      recent genetic associations with TIH, and thoughts on management of the
      condition. RECENT FINDINGS: Recent genetic and phenotyping analysis has suggested
      that prostaglandin E2 pathways in the collecting duct may have a role in the
      development of TIH in a subgroup of patients. Greater understanding of the
      molecular pathophysiology of TIH raises the prospect of pre-prescription TIH risk
      profiling and may offer novel insights into how TIH may be avoided, prevented and
      treated. The rising prevalence of hypertension and the widespread use of
      thiazides mean that further understanding of TIH will continue to be a pressing
      issue for patients, physicians, and scientists alike for the foreseeable future.

PMID- 29637414
TI  - Dermatomyositis Clinical and Pathological Phenotypes Associated with Myositis
      Specific Autoantibodies.
AB  - PURPOSE OF REVIEW: Dermatomyositis is an idiopathic inflammatory myopathy with a
      variety of systemic and cutaneous manifestations. The myositis-specific
      autoantibodies (MSAs) are associated with phenotypic features and provide a tool
      for sub-classification of dermatomyositis patients. This review focuses on recent
      work characterizing the clinical features that accompany the MSAs in
      dermatomyositis. RECENT FINDINGS: There is increasing recognition of the distinct
      clinical and pathological phenotypes associated with each MSA. Most of these
      features display considerable overlap between MSA groups. Despite this, there are
      notable differences between the typical combinations of cutaneous and systemic
      manifestations, response to therapy, prognosis, and disease sequelae that define
      each dermatomyositis MSA group. The MSAs may ultimately improve diagnosis and sub
      classification of dermatomyositis patients. However, more work is needed to
      understand the pathologic basis for much of the heterogeneity found within these
      subgroups.

PMID- 29637416
TI  - Molecular cloning, polymorphism, and expression analysis of the LKB1/STK11 gene
      and its association with non-specific digestive disorder in rabbits.
AB  - Liver kinase B1 (LKB1, also called STK11) encodes a serine/threonine kinase
      mutated in Peutz-Jeghers cancer syndrome characterized by gastrointestinal
      polyposis. Although LKB1 plays an important role in regulating energy
      homeostasis, cell growth, and metabolism via activation of adenosine
      monophosphate (AMP)-activated protein kinase (AMPK), nothing is known about its
      molecular characteristics and possible involvement in non-specific digestive
      disorder (NSDD) of rabbits. In the present study, we first cloned the coding
      sequence (CDS) of rabbit LKB1, which consisted of 1317 bp encoding 438 amino
      acids (AAs) and contained a highly conserved S_TKc kinase domain. Its deduced AA
      sequence showed 87.93-91.10% similarities with that of other species. In order to
      determine its involvement in NSDD, a NSDD rabbit model was built by a dietary
      fiber deficiency. The polymorphic site of LKB1 was then investigated in both
      healthy and NSDD groups using directing sequencing. Our results suggested that a
      synonymous variant site (840 c. G > C, CCC->CCG) existed in its S_TKc domain,
      which was associated with susceptibility to NSDD. Furthermore, qPCR was utilized
      to examine the mRNA levels of LKB1 and its downstream targets (i.e., PRKAA2, mTOR
      and NF-kbeta) in several intestinal-related tissues from both healthy and NSDD
      groups. Significant changes in their expression levels between two groups
      indicated that impaired LKB1 signaling contributed to the intestinal abnormality
      in NSDD rabbits. Taken together, it could be concluded that LKB1 might be a
      potential candidate gene affecting the occurrence of rabbit NSDD. This
      information may serve as a basis for further investigations on rabbit digestive
      diseases.

PMID- 29637417
TI  - Gun carrying among freshmen and sophomores in Chicago, New York City and Los
      Angeles public schools: the Youth Risk Behavior Survey, 2007-2013.
AB  - BACKGROUND: This study evaluated trends and risk factors over time for self
      reported gun carrying among freshman and sophomore public school students in
      Chicago, New York City and Los Angeles, chosen as high profile cities with
      different levels of firearm violence. METHODS: The study used four biennial waves
      (2007-2013) of the Youth Risk Behavior Survey (YRBS), an anonymous, voluntary
      survey of public high school students. Analyses were restricted to freshman and
      sophomores given significant high school dropout rates among older students.
      School population weighted results are presented based on the YRBS complex survey
      design, including comparisons of reported gun carrying across survey waves and
      cities. A violence index was created from eight survey items that capture
      students' perceived threat level. Chi square tests and multivariable Poisson
      regression analyses were used to test the significance of differences across
      cities and over time in the likelihood of gun carrying controlling for
      sociodemographic characteristics, mental health risk factors and behavioral risk
      factors. RESULTS: The study included a total weighted population estimate of
      1,137,449 students across the three cities and four survey waves. Mean self
      reported gun carrying across all survey waves was 8.89% in Chicago, 4.09% in New
      York City, and 6.03% in Los Angeles (p < 0.001). There were no significant
      changes in gun carrying prevalence within each individual city over the survey
      waves. Multivariable Poisson regression estimates showed increased likelihood for
      gun carrying among males (IRR 1.41, CI 1.27-1.58), among non-Hispanic Blacks (IRR
      1.26, CI 1.07-1.48), and among those who reported a higher violence index. Each
      additional violence index count increase was associated with a 1.74 times (CI
      1.70-1.78) increased likelihood for gun carrying. CONCLUSIONS: There was a much
      higher self-reported rate of gun carrying and a higher burden of violence
      exposure in Chicago as compared to New York City and Los Angeles. Students'
      exposure to violence extended to other stressors illuminated by the YRBS
      including fighting, perceptions of safety, and other high-risk behaviors. Through
      the violence index we created, we are better able to categorize the most high
      risk individuals and describe the magnitude of their increased likelihood to
      carry a gun.

PMID- 29637418
TI  - Pre-diagnostic changes in body mass index and mortality among breast cancer
      patients.
AB  - PURPOSE: We investigated whether changes in body mass index (BMI) before a breast
      cancer diagnosis affected mortality and whether trajectories more accurately
      predict overall mortality compared to a single measure of BMI. METHODS: Our
      prospective cohort comprised 2012 women with breast cancer who reported their
      weight in each decade from 20 to 50-64 years of age. We used trajectory analysis
      to identify groups with similar development patterns in BMI and Cox proportional
      hazards models to examine the association between trajectory groups and
      mortality, and interactions with oestrogen receptor status and smoking. We used c
      index statistics to compare the trajectory model with the single measure model of
      BMI. RESULTS: We identified three distinct trajectory groups, with a mean BMI at
      age 20 of 19, 22 and 24 increasing to 23 (normal-to-normal), 29 (normal-to
      overweight) and 37 (normal-to-obese) at 50-64 years of age, respectively. Women
      in the normal-to-obese trajectory group experienced significantly higher overall
      mortality than those in the normal-to-normal trajectory group (HR 1.76, 95% CI
      1.21-2.56). The association declined to a non-significant level after adjustments
      for clinical prognostic factors. Although not significant, the same tendency was
      seen for breast cancer-specific mortality. The association was strongest in women
      with oestrogen receptor-negative tumours. Weight changes over time were not
      significantly different from a single BMI measure before diagnosis to predict
      survival. CONCLUSION: Weight gain affects overall mortality after breast cancer
      but clinical prognostic factors largely eliminate the association. Using
      trajectories of weight changes did not improve the predictive value compared to a
      single measure of BMI.

PMID- 29637420
TI  - Cross sectional analysis of Chicago vs suburban Cook County suicide deaths among
      10-24-year-olds in the Illinois violent death reporting system.
AB  - BACKGROUND: In 2014, suicide was the second leading cause of death among 10- to
      24-year-olds in the US. Studies note disparities in youth suicide based on sex,
      race/ethnicity, and urban vs rural settings. This study investigates
      demographics, mental health indicators, and other circumstances surrounding
      youth/young adult deaths by suicide, comparing Chicago and suburban Cook County
      from 2005 to 2010. METHODS: Using the Illinois Violent Death Reporting System
      (IVDRS), we employed a cross-sectional design to provide descriptive analysis of
      decedents in three age groups (10-14, 15-19, and 20-24 years) in two geographic
      areas: urban (city of Chicago) and suburban (suburban Cook County) between
      January 1, 2005 and December 31, 2010. We used chi-square testing to test for
      significant differences in each age group by demographics, mental health
      indicators, and suicide markers in each area. RESULTS: Between 2005 and 2010, the
      IVDRS reported 299 deaths by suicide among 10-24-year-olds, 52% in Chicago, and
      48% in suburban Cook County. Of these deaths, 5.7%, 33.4% and 60.9% were ages 10
      14, 15-19, and 20-24 years, respectively. Non-Hispanic (NH) whites comprised
      50.7% of the totals, NH Blacks 26.5%, Hispanics 16.8%, and Asians 5.7%. In
      Chicago, males were 84% of suicides and 62.7% in suburban Cook County among 15-19
      year-olds (p < 0.05). White race was significantly different in 10-14-year-olds:
      0% in Chicago, 54% in suburban Cook County (p < 0.05). Racial and ethnic
      differences in suicides among 15-19-year-olds in Chicago vs suburban Cook County
      were: NH White 22.4% vs 74.5% (p < 0.001), NH Black 46.9% vs 13.7% (p < 0.05),
      Hispanic 24.5% vs 7.8% (p < 0.05). There were also differences for 20-24-year
      olds with NH White 43% vs 65.4% and NH Black 32% vs 13.6% (p < 0.05 for both).
      For mechanism of death, in 15-19-year-olds, there were differences between city
      and suburban in firearm deaths (42.9% vs 20%, p < 0.05) and in poisoning (0 vs
      14%, p < 0.05). CONCLUSIONS: Our analyses detected significant location-related
      differences in the characteristics of decedents within the Chicago region
      indicating that local data are needed to inform suicide prevention efforts so
      that those at most risk can be prioritized for services. IVDRS is a potent tool
      in identifying these variations.

PMID- 29637419
TI  - The Endothelin System: A Critical Player in the Pathophysiology of Preeclampsia.
AB  - PURPOSE OF REVIEW: Preeclampsia (PE) is a disorder of pregnancy typically
      characterized by new-onset hypertension and proteinuria after gestational week
      20. Although preeclampsia is one of the leading causes of maternal and perinatal
      morbidity and death worldwide, the mechanisms of the pathogenesis of the disorder
      remain unclear and treatment options are limited. Placental ischemic events and
      the release of placental factors appear to play a critical role in the
      pathophysiology. These factors contribute to a generalized systemic vascular
      endothelial dysfunction and result in increased systemic vascular resistance and
      hypertension. RECENT FINDINGS: There is increasing evidence to suggest that
      endothelin-1 (ET-1) in the maternal vascular endothelium is a critical final
      common pathway, whereby placental ischemic factors cause cardiovascular and renal
      dysfunction in the mother. Multiple studies report increased levels of ET-1 in
      PE. A number of experimental models of PE are also associated with elevated
      tissue levels of prepro-ET-1 mRNA. Moreover, experimental models of PE (placental
      ischemia, sFlt-1 excess, TNF-alpha excess, and AT1-AA infusion) have proven to be
      responsive to ET type A receptor antagonism. Recent studies also suggest that
      abnormalities in ET type B receptor signaling may also play a role in PE.
      Although numerous studies highlight the importance of the ET system in the
      pathogenesis of PE, further work is needed to determine whether ET receptor
      antagonists could provide an effective therapy for the management of this
      disease.

PMID- 29637421
TI  - The Efficacy of a Universal School-Based Prevention Program for Eating Disorders
      among German Adolescents: Results from a Randomized-Controlled Trial.
AB  - Disordered eating is highly prevalent during adolescence and has a detrimental
      effect on further development. Effective prevention programs are needed to
      prevent unhealthy developmental trajectories. This study evaluated the efficacy
      of the POPS-program (POtsdam Prevention at Schools), a universal school-based
      eating disorder prevention program for adolescents. In a cluster-randomized
      design, we compared the intervention group receiving the prevention program to a
      waiting control group. Outcomes included indicators of disordered eating and
      relevant risk factors for eating disorders (body dissatisfaction, internalization
      of the thin ideal, perceived media pressure, perfectionism, emotional element of
      exercise, social comparison, and perceived teasing). Questionnaires were
      administered at the start of the intervention, 3 and 12 months post intervention.
      At baseline, 1112 adolescents aged 10 to 16 years participated (49% girls; 51%
      intervention group). Intention-to-treat analyses with the complete data set and
      per-protocol analyses as a completer analysis were performed. The intervention
      group showed a more favorable course compared to the control group regarding all
      observed risk factors for eating disorders except for perceived teasing. Effect
      sizes were small but comparable to other primary prevention programs. At 1-year
      follow-up, a small but significant effect on disordered eating was observed.
      Results of the per-protocol analyses were mostly confirmed by the intention-to
      treat analyses. Results were promising for both genders although girls benefited
      more regarding disordered eating and internalization of the thin ideal. Further
      studies are warranted examining successful program elements and whether gender
      specific programs are needed.

PMID- 29637422
TI  - You can have your breastmilk and safe sleep too: a preliminary analysis of infant
      safe sleep data in a Midwestern home visiting program.
AB  - BACKGROUND: Sudden unexpected infant death (SUID) accounted for approximately
      3700 infant deaths in the US in 2015. SUID risk factors include prone sleeping,
      bed-sharing, soft bedding use, and maternal smoking. Infant safe sleep data in at
      risk communities are difficult to obtain and home visiting programs can add to
      what we know. This study's purpose is to determine how often caregivers enrolled
      in home visiting programs provide safe sleep environments for their infants in
      relation to breastfeeding status and tobacco use. METHODS: Female caregivers in
      at-risk communities were prospectively enrolled in Midwestern home visiting
      programs. Those that had infants < 365 days old and completed a safe sleep survey
      between October 1, 2016 and May 18, 2017 were included. Caregivers' responses
      (always, sometimes, or never) to three safe sleep questions were compared by
      breastfeeding status, caregiver tobacco use, and household tobacco use using
      Pearson's chi-squared or Fisher's exact test. RESULTS: The characteristics of the
      289 eligible female caregivers included 120 (42%) <= 21 years old, 137 (47%)
      black, 77 (27%) breastfeeding, and 60 (22%) with household tobacco use. Two
      hundred forty-six (85%) caregivers always placed infants in the supine position,
      148 (51%) never bed-shared, and 186 (64%) never used soft bedding. Ongoing
      breastfeeding caregivers never bed-shared more often than those who never
      breastfed or weaned (66% vs. 53% vs. 39%, p = 0.003). Households with tobacco use
      placed infants in the supine position less (75% vs. 88%, p = 0.03), bed-shared
      more (62% vs. 44%, p = 0.04), and used soft bedding more (50% vs. 32%, p = 0.004)
      relative to those without tobacco use. CONCLUSIONS: In this group of at-risk
      young mothers, those who breastfed bed-shared less than mothers who were not
      breastfeeding; this finding has implications toward reducing the SUID risk in
      similar populations. This study also demonstrated that infants living with a
      tobacco user are less likely to be sleeping safely. This suggests that a
      multifaceted approach to safe sleep counseling may be needed.

PMID- 29637423
TI  - First report on cystacanths of Sphaerirostris lanceoides (Petrochenko, 1949)
      (Acanthocephala: Centrorhynchidae) from the Asiatic toad Bufo gargarizans Cantor
      (Amphibia: Anura) in China.
AB  - Everted cystacanths of Sphaerirostris lanceoides (Petrochenko, 1949) Golvan 1956
      are reported from the Asiatic toad Bufo gargarizans Cantor (Amphibia: Anura) for
      the first time. The prevalence was 1.96% and the intensity ranged between 1.0-3.0
      acanthocephalans. SEM observations revealed the morphology of the gonopore and
      the presence of a flat, bare region on the apical part of the proboscis.
      Moreover, S. lanceoides was characterised using molecular approaches by
      sequencing the ribosomal ITS1-5.8S-ITS2 region and the mitochondrial cox1 gene.
      The resulting ITS sequences were identical and the cox1 sequences showed a
      divergence of 0-0.75%. Sphaerirostris lanceoides is the first species of the
      genus for which the ITS1-5.8S-ITS2 and cox1 loci have been sequenced to aid
      species identification.

PMID- 29637424
TI  - [Cultural differences concerning depressive disorders and attachment dimensions].
AB  - BACKGROUND: Attachment is a psychological parameter across cultures and is
      influenced by childhood experiences. Though the construct of attachment tends to
      certain stability, different influences, like culture, can change the quality of
      attachment during lifetime. As can be seen from the example of depression in
      adulthood the clinical symptoms of this disorder may be different due to the
      cultural background. METHODS: The present study focuses on inter- and
      intracultural differences concerning the attachment qualities of Turkish people
      in the homeland, Turkish migrants in Austria and Austrians (N = 297) by using the
      self-assessment questionnaire RSQ. Each ethnic group consisted of a healthy
      control group (N = 153) as well as a patient group currently suffering from a
      depressive episode (N = 144) and were getting an in or outpatient treatment.
      OBJECTIVE: The hypothesis tested was whether culture moderates a correlation
      between depressive disorders and attachment abilities. RESULTS: There were
      significant differences in attachment ability between cultures whereby controls
      presented significantly more secure attachment ability in all parameters compared
      to patients. While the Austrian control group showed the most secure attachment
      orientation, the Austrian patients had the highest level of insecurity, followed
      by the migrant group. However, the comparison of healthy and depressive Turks
      revealed no significant differences. CONCLUSION: Thus, culture shows significant
      effects concerning depressive disorders and attachment dimensions.

PMID- 29637425
TI  - Investigation of contrast-enhanced subtracted breast CT images with MAP-EM based
      on projection-based weighting imaging.
AB  - Contrast-enhanced subtracted breast computer tomography (CESBCT) images acquired
      using energy-resolved photon counting detector can be helpful to enhance the
      visibility of breast tumors. In such technology, one challenge is the limited
      number of photons in each energy bin, thereby possibly leading to high noise in
      separate images from each energy bin, the projection-based weighted image, and
      the subtracted image. In conventional low-dose CT imaging, iterative image
      reconstruction provides a superior signal-to-noise compared with the filtered
      back projection (FBP) algorithm. In this paper, maximum a posteriori expectation
      maximization (MAP-EM) based on projection-based weighting imaging for
      reconstruction of CESBCT images acquired using an energy-resolving photon
      counting detector is proposed, and its performance was investigated in terms of
      contrast-to-noise ratio (CNR). The simulation study shows that MAP-EM based on
      projection-based weighting imaging can improve the CNR in CESBCT images by 117.7%
      121.2% compared with FBP based on projection-based weighting imaging method. When
      compared with the energy-integrating imaging that uses the MAP-EM algorithm,
      projection-based weighting imaging that uses the MAP-EM algorithm can improve the
      CNR of CESBCT images by 10.5%-13.3%. In conclusion, MAP-EM based on projection
      based weighting imaging shows significant improvement the CNR of the CESBCT image
      compared with FBP based on projection-based weighting imaging, and MAP-EM based
      on projection-based weighting imaging outperforms MAP-EM based on energy
      integrating imaging for CESBCT imaging.

PMID- 29637426
TI  - Kinetics study of nicosulfuron degradation by a Pseudomonas nitroreducens strain
      NSA02.
AB  - A bacterial strain NSA02, isolated from contaminated soil and identified as
      Pseudomonas nitroreducens based on partial 16S rDNA gene sequence analysis and
      BIOLOG microbiology analysis, was used to study biodegradation of nicosulfuron in
      the culture medium. The optimal degradation conditions were determined to be 30 
      degrees C and pH 7.0. Batch tests were performed for seven different initial
      substrate concentrations to observe substrate degradation and associated cell
      growth. The biodegradation kinetics was found to follow a first-order model with
      regression values greater than 0.98. Specific degradation rate and specific
      growth rate of bacterial cells were observed to follow substrate inhibition
      kinetics, and the maximum values of both rates were observed at 100 mg L-1 of
      nicosulfuron concentration. Kinetic parameters of three substrate inhibition
      models (Haldane, Aiba-Edwards and Teissier-Edwards) were fitted to the
      relationship between those rates and substrate concentrations. With the date
      obtained, Haldane and Teissier-Edwards models provide better representation when
      compared to Aiba-Edwards model. Inoculating nicosulfuron-treated soil samples
      with strain NSA02 resulted in a 5-6 times higher rate of nicosulfuron removal
      than that in non-inoculated soil. Five metabolites of nicosulfuron degradation
      were detected and identified by liquid chromatography mass spectrometry, and
      three possible biotransformation pathways were proposed. These results highlight
      the potential of the isolated bacterium to be used in the bioremediation of
      nicosulfuron-contaminated soils.

PMID- 29637427
TI  - Child abuse and neglect experts' determination of when a child being left home
      alone constitutes child neglect.
AB  - BACKGROUND: Only 14 states have laws or guidelines regarding the minimum age a
      child may be left home alone. These ages range from 6 to 14 years. Our objective
      was to identify factors that influence child neglect determination by experts
      with regards to parents leaving children home alone. METHODS: American Academy of
      Pediatrics Section on Child Abuse and Neglect members (N = 523) were surveyed
      from July-August, 2015. Respondents were asked whether scenarios involving a
      child of varying age knowingly left home alone for 4 h were neglect in the
      presence or absence of injury to the child and the legality of the situation.
      Comparisons were performed using the chi-square test. RESULTS: One hundred ninety
      three members responded (36.9%). In the scenario where there were no relevant
      laws and the child was uninjured, nearly 100% of the child experts determined
      this as being child neglect when the child was 6 years old. For 8, 10, 12, and 14
      year olds, this was 88, 48, 4, and 1%, respectively. However, a significantly
      higher percentage of experts considered it child neglect for most ages when there
      was a law making the scenario illegal as compared when there was no law, and when
      the child was injured versus when they were not. The only demographic variable
      that showed a difference in child neglect determination was that females were
      more likely to consider higher aged children as having been neglected when there
      were no laws but the child was injured. The vast majority of experts (85%) stated
      that leaving a child home alone for 4 h should be illegal if the child is < 9
      years old, and nearly one-half (44%) said it should be illegal for children < 11
      years old. CONCLUSIONS: A number of factors affect how experts view children
      being left home alone as potential child neglect. Our data suggests that such
      cases may be evaluated differently due to variations in state laws, even though
      the risk to the child is the same. These results call for child safety law reform
      to provide greater uniformity in the evaluation of potential child neglect cases
      and better protect the safety of children.

PMID- 29637428
TI  - Characterization of HIV-1 subtypes and transmitted drug resistance among
      treatment-naive HIV-infected individuals in Zhejiang, China, 2014-2017.
AB  - In recent years, transmitted drug resistance (TDR) has adversely impacted upon
      first-line therapy for HIV-infected individuals. To understand the current
      subtype distribution and TDR level in Zhejiang, China we performed phylogenetic
      analysis and genotypic drug resistance testing of treatment-naive HIV-infected
      individuals. A total of 153 HIV-1 Pol genes were successfully amplified. The
      distribution of HIV-1 genotypes was as follows: CRF01_AE (43.8%); CRF07_BC
      (37.9%); subtype B/B' (7.2%); CRF08_BC (5.2%); and others (5.9%). Drug resistance
      analysis demonstrated that 11.1% of isolates contained at least one NRTI or NNRTI
      resistance-associated mutations while 2.0% were identified to be resistant to
      PIs. These findings enhance our understanding of the genetic diversity of HIV-1
      strains circulating in Zhejiang and provide some guidelines for HIV initial
      treatment therapy.

PMID- 29637430
TI  - Correction to: Progressive multifocal leukoencephalopathy in rituximab-treated
      rheumatic diseases: a rare event.
AB  - The article "Progressive multifocal leukoencephalopathy in rituximab-treated
      rheumatic diseases: a rare event," written by Joseph R. Berger, Vineeta Malik,
      Stuart Lacey, Paul Brunetta, and Patricia B. Lehane3, was originally published
      electronically on the publisher's internet portal (currently SpringerLink).

PMID- 29637431
TI  - Pediatric falls ages 0-4: understanding demographics, mechanisms, and injury
      severities.
AB  - BACKGROUND: Pediatric unintentional falls are the leading cause of injury-related
      emergency visits for children < 5 years old. The purpose of this study was to
      identify population characteristics, injury mechanisms, and injury severities and
      patterns among children < 5 years to better inform age-appropriate falls
      prevention strategies. METHODS: This retrospective database study used trauma
      registry data from the lead pediatric trauma system in Georgia. Data were
      analyzed for all patients < 5 years with an international classification of
      disease, 9th revision, clinical modification (ICD-9 CM) external cause of injury
      code (E-code) for unintentional falls between 1/1/2013 and 12/31/2015. Age
      (months) was compared across categories of demographic variables, injury
      mechanisms, and emergency department (ED) disposition using Kruskal-Wallis ANOVA
      and the Mann Whitney U test. The relationships between demographic variables,
      mechanism of injury (MOI), and Injury Severity Score (ISS) were evaluated using
      multinomial logistic regression. RESULTS: Inclusion criteria were met by 1086
      patients (median age = 28 months; 59.7% male; 53.8% White; 49.1% <  1 m fall
      height). Younger children, < 1-year-old, primarily fell from caregiver's arms,
      bed, or furniture, while older children sustained more falls from furniture and
      playgrounds. Children who fell from playground equipment were older (median = 49
      months, p < 0.01) than those who fell from the bed (median = 10 months), stairs
      (median = 18 months), or furniture (median = 19 months). Children < 1 year had
      the highest proportion of head injuries including skull fracture (63.1%) and
      intracranial hemorrhage (65.5%), 2-year-old children had the highest proportion
      of femur fractures (32.9%), and 4-year-old children had the highest proportion of
      humerus fractures (41.0%). Medicaid patients were younger (median = 24.5 months,
      p < 0.01) than private payer (median = 34 months). Black patients were younger
      (median = 20.5 months, p < 0.001) than White patients (median = 29 months).
      Results from multinomial logistic regression models suggest that as age
      increases, odds of a severe ISS (16-25) decreased (OR = 0.95, CI = 0.93-0.97).
      CONCLUSIONS: Pediatric unintentional falls are a significant burden of injury for
      children < 5 years. Future work will use these risk and injury profiles to inform
      current safety recommendations and develop evidence-based interventions for
      parents/caregivers and pediatric providers.

PMID- 29637432
TI  - Early gastric cancer with lymphoid stroma presenting as a subepithelial lesion
      diagnosed by endoscopic submucosal dissection.
AB  - A 53-year-old man underwent an esophagogastroduodenoscopy that showed a 20-mm
      subepithelial lesion in the middle gastric body. Endoscopic ultrasound revealed a
      hypoechoic mass located in the submucosa. Biopsy specimens revealed a benign
      gastric mucosa with severe lymphocytic infiltration in the submucosa. Malignant
      lymphoma or gastric cancer with lymphoid stroma was suspected. We performed
      endoscopic submucosal dissection for definitive diagnosis. Histological
      examination showed undifferentiated adenocarcinoma, which showed positive Epstein
      Barr virus-encoded RNA in situ hybridization results, invading the submucosa
      mixed with dense lymphocytic infiltration. Thus, Epstein-Barr virus-positive
      gastric cancer with lymphoid stroma was diagnosed. Gastric cancer with lymphoid
      stroma is a rare subtype of gastric cancer, which is associated with Epstein-Barr
      virus infection; it sometimes appears as a subepithelial lesion, which makes it
      difficult to diagnose using standard biopsy. Endoscopic submucosal dissection was
      useful in obtaining a sufficient tissue for full histological assessment,
      including immunostaining.

PMID- 29637433
TI  - Socio-Economic Status and Prevalence of Self-Reported Osteoporosis in Tehran:
      Results from a Large Population-Based Cross-Sectional Study (Urban HEART-2).
AB  - Osteoporosis is a widespread disease among older peoples. The aim of this study
      is to estimate the prevalence of self-reported osteoporosis and assessing its
      association with socio-economic status. A population-based cross-sectional study
      was conducted in Tehran, Iran in 2011. Participants were 45,990 individuals aged
      above 20 years from 22 urban districts. Osteoporosis was measured by self
      administrative questionnaire. Wealth index was constructed using principal
      component analysis based on household assets. Chi-square test, chi square test
      for trend, and crude odds ratio were used to assess associations in univariate
      analysis. Multiple logistic regression utilized to estimate adjusted associations
      between self-reported osteoporosis and socio-economic status.The overall
      estimated prevalence of self-reported osteoporosis was 4% (95% CI 3.88-4.13),
      1.19% in men, and 6.84% in women (P < 0.001). The prevalence increased
      considerably as age increased (P for trend < 0.001). In multivariable analysis,
      education and wealth status were negative, and smoking was positively associated
      with the prevalence of self-reported osteoporosis. No association was found
      between participants' skill levels and Townsend deprivation index with the
      prevalence of self-reported osteoporosis.The findings of the present study have
      improved understanding of the association between socioeconomic status and
      osteoporosis in the Iranian population. It is important to consider socioeconomic
      status in screening and prevention programs.

PMID- 29637434
TI  - The Impact of Health Messages on Maternal Decisions About Infant Sleep Position:
      A Randomized Controlled Trial.
AB  - Sudden infant death syndrome (SIDS) rates in African-Americans are more than
      twice national rates, and historically, African-American parents are more likely
      than other groups to place infants prone, even when they are aware of supine
      sleep recommendations. Prior studies have shown African-Americans have low self
      efficacy against SIDS but high self-efficacy against suffocation. This study
      aimed to determine the impact of a specific health message about suffocation
      prevention on African-American parental decisions regarding infant sleep
      position. We conducted a randomized controlled trial of 1194 African-American
      mothers, who were randomized to receive standard messages about safe sleep
      practices to reduce the risk of SIDS, or enhanced messages about safe sleep
      practices to prevent SIDS and suffocation. Mothers were interviewed about
      knowledge and attitude, self-efficacy and current infant care practices when
      infants were 2-3 weeks, 2-3 months and 5-6 months old. Analyses of covariance
      were conducted to estimate the change in knowledge, attitudes and practice in
      each group, and chi square tests were used to compare sleep position with each
      variable. Over the first 6 months, the proportion of African-American infants
      placed supine gradually decreased and was unchanged by enhanced education about
      SIDS, suffocation risk and sleep safety. While initially high self-efficacy
      against SIDS and suffocation correlated with supine positioning, by 5-6 months
      self-efficacy did not correspond to sleep position in either group.

PMID- 29637429
TI  - Taxonomy of the order Mononegavirales: update 2018.
AB  - In 2018, the order Mononegavirales was expanded by inclusion of 1 new genus and
      12 novel species. This article presents the updated taxonomy of the order
      Mononegavirales as now accepted by the International Committee on Taxonomy of
      Viruses (ICTV) and summarizes additional taxonomic proposals that may affect the
      order in the near future.

PMID- 29637435
TI  - The Influence of Breast Tumour-Derived Factors and Wnt Antagonism on the
      Transformation of Adipose-Derived Mesenchymal Stem Cells into Tumour-Associated
      Fibroblasts.
AB  - Within the tumour stroma, a heterogeneous population of cell types reciprocally
      regulates cell proliferation, which considerably affects the progression of the
      disease. In this study, using tumour conditioned medium (TCM) derived from breast
      tumour cell lines - MCF7 and MDA MB 231, we have demonstrated the differentiation
      of adipose-derived mesenchymal stem cells (ADSCs) into tumour-associated
      fibroblasts (TAFs). Since the Wnt signalling pathway is a key signalling pathway
      driving breast tumour growth, the effect of the Wnt antagonist secreted frizzled
      related protein 4 (sFRP4) was also examined. The response of ADSCs to TCM and
      sFRP4 treatments was determined by using cell viability assay to determine the
      changes in ADSC viability, immunofluorescence for mesenchymal markers, glucose
      uptake assay, and glycolysis stress test using the Seahorse Extracellular Flux
      analyser to determine the glycolytic activity of ADSCs. ADSCs have been shown to
      acquire a hyper-proliferative state, significantly increasing their number upon
      short-term and long-term exposure to TCM. Changes have also been observed in the
      expression of key mesenchymal markers as well as in the metabolic state of ADSCs.
      SFRP4 significantly inhibited the differentiation of ADSCs into TAFs by reducing
      cell growth as well as mesenchymal marker expression (cell line-dependent).
      However, sFRP4 did not induce further significant changes to the altered
      metabolic phenotype of ADSCs following TCM exposure. Altogether, this study
      suggests that the breast tumour milieu may transform ADSCs into a tumour
      supportive phenotype, which can be altered by Wnt antagonism, but is independent
      of metabolic changes.

PMID- 29637437
TI  - Extramural Venous Invasion in Patients with Locally Advanced Esophageal Cancer: A
      Reminder to Pathologists to Look Harder.

PMID- 29637436
TI  - Opioid Prescribing After Curative-Intent Surgery: A Qualitative Study Using the
      Theoretical Domains Framework.
AB  - BACKGROUND: Excessive opioid prescribing is common after curative-intent surgery,
      but little is known about what factors influence prescribing behaviors among
      surgeons. To identify targets for intervention, we performed a qualitative study
      of opioid prescribing after curative-intent surgery using the Theoretical Domains
      Framework, a well-established implementation science method for identifying
      factors influencing healthcare provider behavior. METHODS: Prior to data
      collection, we constructed a semi-structured interview guide to explore decision
      making for opioid prescribing. We then conducted interviews with surgical
      oncology providers at a single comprehensive cancer center. Interviews were
      recorded, transcribed verbatim, then independently coded by two investigators
      using the Theoretical Domains Framework to identify theoretical domains relevant
      to opioid prescribing. Relevant domains were then linked to behavior models to
      select targeted interventions likely to improve opioid prescribing. RESULTS:
      Twenty-one subjects were interviewed from November 2016 to May 2017, including
      attending surgeons, resident surgeons, physician assistants, and nurses. Five
      theoretical domains emerged as relevant to opioid prescribing: environmental
      context and resources; social influences; beliefs about consequences;
      social/professional role and identity; and goals. Using these domains, three
      interventions were identified as likely to change opioid prescribing behavior:
      (1) enablement (deploy nurses during preoperative visits to counsel patients on
      opioid use); (2) environmental restructuring (provide on-screen prompts with
      normative data on the quantity of opioid prescribed); and (3) education (provide
      prescribing guidelines). CONCLUSIONS: Key determinants of opioid prescribing
      behavior after curative-intent surgery include environmental and social factors.
      Interventions targeting these factors are likely to improve opioid prescribing in
      surgical oncology.

PMID- 29637439
TI  - Correction to: Reduced Value-Driven Attentional Capture among Children with ADHD
      Compared to Typically Developing Controls.
AB  - The authors would like to correct a few minor errors in our article, none of
      which change the conclusions or interpretations presented.

PMID- 29637438
TI  - Peritoneal Carcinomatosis of Rare Ovarian Origin Treated by Cytoreductive Surgery
      and Hyperthermic Intraperitoneal Chemotherapy: A Multi-Institutional Cohort from
      PSOGI and BIG-RENAPE.
AB  - PURPOSE: Ovarian cancer is the most common deadly cancer of gynecologic origin.
      Patients often are diagnosed at advanced stage with peritoneal metastasis. There
      are many rare histologies of ovarian cancer; some have outcomes worse than serous
      ovarian cancer. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal
      chemotherapy (HIPEC) can be considered for patients with recurrence. This study
      was designed to assess the impact of CRS and HIPEC on survival of patient with
      peritoneal metastasis from rare ovarian malignancy. METHODS: A prospective,
      multicentric, international database was retrospectively searched to identify all
      patients with rare ovarian tumor (mucinous, clear cells, endometrioid, small cell
      hypercalcemic, and other) and peritoneal metastasis who underwent CRS and HIPEC
      through the Peritoneal Surface Oncology Group International (PSOGI) and BIG
      RENAPE working group. The postoperative complications, long-term results, and
      principal prognostic factors were analyzed. RESULTS: The analysis included 210
      patients with a median follow-up of 43.5 months. Median overall survival (OS) was
      69.3 months, and the 5-year OS was 57.7%. For mucinous tumors, median OS and DFS
      were not reached at 5 years. For granulosa tumors, median overall survival was
      not reached at 5 years, and median DFS was 34.6 months. Teratoma or germinal
      tumor showed median overall survival and DFS that were not reached at 5 years.
      Differences in OS were not statistically significant between histologies (p =
      0.383), whereas differences in DFS were (p < 0.001). CONCLUSIONS: CRS and HIPEC
      may increases long-term survival in selected patients with peritoneal metastasis
      from rare ovarian tumors especially in mucinous, granulosa, or teratoma
      histological subtypes.

PMID- 29637440
TI  - Bexarotene Modulates Retinoid-X-Receptor Expression and Is Protective Against
      Neurotoxic Endoplasmic Reticulum Stress Response and Apoptotic Pathway
      Activation.
AB  - Retinoid X-receptors (RXRs) are members of the ligand-dependent transcription
      factor family of nuclear receptors that have gained recent research focus as
      potential targets for neurodegenerative disorders. Bexarotene is an RXR
      pharmacological agonist that is shown to be neuroprotective through its effects
      in promoting amyloid beta (Abeta) uptake by the glial cells in the brain. This
      study aimed to evaluate the dose-dependent effects of bexarotene on RXR
      expression in SH-SY5Y neuroblastoma cells and validate the drug effects in the
      brain in vivo. The protein expression studies were carried out using a
      combination of various drug treatment paradigms followed by expression analysis
      using Western blotting and immunofluorescence. Our study demonstrated that
      bexarotene promoted the expression of RXR alpha, beta and gamma isoforms at
      optimal concentrations in the cells and in the mice brain. Interestingly, a
      decreased RXR expression was identified in Alzheimer's disease mouse model and in
      the cells that were treated with Abeta. Bexarotene treatment not only rescued the
      RXR expression loss caused by Abeta treatment (p < 0.05) but also protected the
      cells against Abeta-induced ER stress (p < 0.05) and pro-apoptotic BAD protein
      activation (p < 0.05). In contrast, higher concentrations of bexarotene
      upregulated the ER stress proteins and led to BAD activation. Our study revealed
      that these downstream neurotoxic effects of high drug concentrations could be
      prevented by pharmacological targeting of the TrkB receptor. The ER stress and
      BAD activation induced by high concentrations of bexarotene were rescued by the
      TrkB agonist, 7,8 dihydroxyflavone (p < 0.05) while TrkB inhibitor CTX-B
      treatment further exacerbated these effects. Together, these findings suggest a
      cross-talk of TrkB signalling with downstream effects of bexarotene toxicity and
      indicate that therapeutic targeting of RXRs could prevent the Abeta-induced
      molecular neurotoxic effects.

PMID- 29637441
TI  - Elevated MeCP2 in Mice Causes Neurodegeneration Involving Tau Dysregulation and
      Excitotoxicity: Implications for the Understanding and Treatment of MeCP2
      Triplication Syndrome.
AB  - Expression of MeCP2 must be carefully regulated as a reduction or increase
      results in serious neurological disorders. We are studying transgenic mice in
      which the MeCP2 gene is expressed at about three times higher than the normal
      level. Male MeCP2-Tg mice, but not female mice, suffer motor and cognitive
      deficits and die at 18-20 weeks of age. MeCP2-Tg mice display elevated GFAP and
      Tau expression within the hippocampus and cortex followed by neuronal loss in
      these brain regions. Loss of Purkinje neurons, but not of granule neurons in the
      cerebellar cortex is also seen. Exposure of cultured cortical neurons to either
      conditioned medium from astrocytes (ACM) derived from male MeCP2-Tg mice or
      normal astrocytes in which MeCP2 is expressed at elevated levels promotes their
      death. Interestingly, ACM from male, but not female MeCP2-Tg mice, displays this
      neurotoxicity reflecting the gender selectivity of neurological symptoms in mice.
      Male ACM, but not female ACM, contains highly elevated levels of glutamate, and
      its neurotoxicity can be prevented by MK-801, indicating that it is caused by
      excitotoxicity. Based on the close phenotypic resemblance of MeCP2-Tg mice to
      patients with MECP2 triplication syndrome, we suggest for the first time that the
      human syndrome is a neurodegenerative disorder resulting from astrocyte
      dysfunction that leads to Tau-mediated excitotoxic neurodegeneration. Loss of
      cortical and hippocampal neurons may explain the mental retardation and epilepsy
      in patients, whereas ataxia likely results from the loss of Purkinje neurons.

PMID- 29637443
TI  - MiR-34a Regulates Axonal Growth of Dorsal Root Ganglia Neurons by Targeting FOXP2
      and VAT1 in Postnatal and Adult Mouse.
AB  - Hyperglycemia impairs nerve fibers of dorsal root ganglia (DRG) neurons, leading
      to diabetic peripheral neuropathy (DPN). However, the molecular mechanisms
      underlying DPN are not fully understood. Using a mouse model of type II diabetes
      (db/db mouse), we found that microRNA-34a (miR-34a) was over-expressed in DRG,
      sciatic nerve, and foot pad tissues of db/db mice. In vitro, high glucose
      significantly upregulated miR-34a in postnatal and adult DRG neurons, which was
      associated with inhibition of axonal growth. Overexpression and attenuation of
      miR-34a in postnatal and adult DRG neurons suppressed and promoted, respectively,
      axonal growth. Bioinformatic analysis suggested that miR-34a putatively targets
      forkhead box protein P2 (FOXP2) and vesicle amine transport 1 (VAT1), which were
      decreased in diabetic tissues and in cultured DRG neurons under high glucose
      conditions. Dual-luciferase assay showed that miR-34a downregulated FOXP2 and
      VAT1 expression by targeting their 3' UTR. Gain-of- and loss-of-function analysis
      showed an inverse relation between augmentation of miR-34a and reduction of FOXP2
      and VAT1 proteins in postnatal and adult DRG neurons. Knockdown of FOXP2 and VAT1
      reduced axonal growth. Together, these findings suggest that miR-34a and its
      target genes of FOXP2 and VAT1 are involved in DRG neuron damage under
      hyperglycemia.

PMID- 29637442
TI  - Impact of Hypoglycemia on Brain Metabolism During Diabetes.
AB  - Diabetes is a metabolic disease afflicting millions of people worldwide. A
      substantial fraction of world's total healthcare expenditure is spent on treating
      diabetes. Hypoglycemia is a serious consequence of anti-diabetic drug therapy,
      because it induces metabolic alterations in the brain. Metabolic alterations are
      one of the central mechanisms mediating hypoglycemia-related functional changes
      in the brain. Acute, chronic, and/or recurrent hypoglycemia modulate multiple
      metabolic pathways, and exposure to hypoglycemia increases consumption of
      alternate respiratory substrates such as ketone bodies, glycogen, and
      monocarboxylates in the brain. The aim of this review is to discuss hypoglycemia
      induced metabolic alterations in the brain in glucose counterregulation, uptake,
      utilization and metabolism, cellular respiration, amino acid and lipid
      metabolism, and the significance of other sources of energy. The present review
      summarizes information on hypoglycemia-induced metabolic changes in the brain of
      diabetic and non-diabetic subjects and the manner in which they may affect brain
      function.

PMID- 29637444
TI  - Bacteroidetes Neurotoxins and Inflammatory Neurodegeneration.
AB  - The gram-negative facultative anaerobe Bacteroides fragilis (B. fragilis)
      constitutes an appreciable proportion of the human gastrointestinal (GI)-tract
      microbiome. As is typical of most gram-negative bacilli, B. fragilis secretes an
      unusually complex mixture of neurotoxins including the extremely pro-inflammatory
      lipopolysaccharide BF-LPS. LPS (i) has recently been shown to associate with the
      periphery of neuronal nuclei in sporadic Alzheimer's disease (AD) brain and (ii)
      promotes the generation of the inflammatory transcription factor NF-kB (p50/p65
      complex) in human neuronal-glial cells in primary-culture. In turn, the NF-kB
      (p50/p65 complex) strongly induces the transcription of a small family of pro
      inflammatory microRNAs (miRNAs) including miRNA-9, miRNA-34a, miRNA-125b, miRNA
      146a, and miRNA-155. These ultimately bind with the 3'-untranslated region (3'
      UTR) of several target messenger RNAs (mRNAs) and thereby reduce their
      expression. Down-regulated mRNAs include those encoding complement factor-H
      (CFH), an SH3-proline-rich multi-domain-scaffolding protein of the postsynaptic
      density (SHANK3), and the triggering receptor expressed in myeloid/microglial
      cells (TREM2), as is observed in sporadic AD brain. Hence, a LPS normally
      confined to the GI tract is capable of driving a NF-kB-miRNA-mediated deficiency
      in gene expression that contributes to alterations in synaptic-architecture and
      synaptic-deficits, amyloidogenesis, innate-immune defects, and progressive
      inflammatory signaling, all of which are characteristics of AD-type
      neurodegeneration. This article will review the most recent research which
      supports the idea that bacterial components of the GI tract microbiome such as BF
      LPS can transverse biophysical barriers and contribute to AD-type change. For the
      first-time, these results indicate that specific GI tract microbiome-derived
      neurotoxins have a strong pathogenic role in eliciting alterations in NF-kB-miRNA
      directed gene expression that drives the AD process.

PMID- 29637445
TI  - Atherosclerotic Renal Artery Stenosis: Should we Intervene Earlier?
AB  - PURPOSE OF REVIEW: Randomized trials have failed to show clinical benefit in
      patients with atherosclerotic renal artery stenosis who were treated with
      angioplasty with or without stenting. However, these studies were done in
      patients with a high-grade stenosis. This paper examines whether there are
      arguments to consider patients with low-grade stenosis for angioplasty. RECENT
      FINDINGS: Patients with low-grade (< 50%) atherosclerotic renal artery stenosis
      have an excess risk for cardiovascular and renal complications. This could be
      related to inflammatory factors being generated by the stenotic kidney. Moreover,
      even a kidney with low-grade stenosis clears less or produces more of the natural
      nitric oxide inhibitor ADMA. Patients with low-grade atherosclerotic renal artery
      stenosis have an increased risk for a variety of complications. In addition, the
      abnormality is progressive. There is a case for setting up a prospective trial to
      examine whether angioplasty confers benefit in patients with low-grade renal
      artery stenosis.

PMID- 29637446
TI  - Effect of high chronic intake of sucrose on liver metabolism in aging rats.
      Modulation by rutin and micronutrients.
AB  - High-sugar intake and senescence share common deleterious effects, in particular
      in liver, but combination of these two factors was little studied. Our aims were
      to examine the effect of a high-sucrose diet in liver of old rats and also the
      potential benefices of a polyphenol/micronutrient supplementation. Four groups of
      22-month-old male rats fed during 5 months with a diet containing either 13 or
      62% sucrose, supplemented or not with rutin, vitamin E, A, D, selenium, and zinc
      were compared. We measured liver macronutrient composition, glycation/oxidative
      stress, enzyme activities (lipogenesis, beta-oxidation, fructokinase), gene
      expression (enzymes and transcription factors), in vivo protein synthesis rates
      and plasma parameters. Sucrose induced an increase in plasma and liver lipid
      content, and a stimulation of liver protein synthesis rates. Gene expression was
      little changed by sucrose, with lower levels for LXR-alpha and LXR-beta.
      Polyphenol/micronutrient supplementation tended to limit liver triglyceride
      infiltration through variations in fatty acid synthase, acyl coA oxidase, and
      possibly ATP-citrate lyase activities. In conclusion, despite differences in
      enzymatic regulations, and blunted responses of gene expression, high-sucrose
      diet was still able to induce a marked increase in liver lipid content in old
      animals. However, it probably attenuated the positive impact of
      polyphenol/micronutrients.

PMID- 29637447
TI  - Thrombomodulin, alarmin signaling, and copeptin: cross-talk between obesity and
      acute ischemic stroke initiation and severity in Egyptians.
AB  - Acute ischemic stroke (AIS) is followed by a strong inflammatory response
      contributing to brain damage and making early diagnosis and treatment inevitable.
      Hence, obesity is a state of chronic inflammation with amplified oxidative
      stress; this study aimed to assess the role played by thrombomodulin (TM)/alarmin
      signaling pathway and copeptin in AIS initiation and severity in addition to the
      implication of abnormal body weight. The study was conducted on 50 participants;
      30 were patients with AIS (15 overweight/obese and 15 normal weight), 10 were
      overweight/obese, and 10 were normal weight. Plasma TM, copeptin, high mobility
      group box1 (HMGB1), and lipocalin 2 (LCN2) levels were immunoassayed. Toll-like
      receptor 4 (TLR4) mRNA expression was evaluated by real-time PCR, National
      Institutes of Health Stroke Scale (NIHSS), carotid intima media thickness;
      atherogenic index and glycemic status were also assessed. TM, copeptin, HMGB1,
      and LCN2 levels were significantly increased in overweight/obese AIS patients and
      in AIS patients with NIHSS score >= 7 when compared to other groups (p value=, ?
      0.001*). Receiver operating characteristic (ROC) curve elaborated HMGB-1 and LCN2
      as the best biomarker for diagnosis and prediction of AIS severity, respectively.
      Regression analysis avails LCN2 and TM as best biomarker for AIS severity
      predication. In conclusion, these results highlighted detrimental role of alarmin
      signaling with increased adaptive response to block this pathway through TM in
      addition to increased copeptin level as an acute damage marker and their tight
      relation to WC not to BMI in AIS which clarify the implication of central
      adiposity.

PMID- 29637448
TI  - The rise of soluble platelet-derived growth factor receptor beta in CSF early
      after subarachnoid hemorrhage correlates with cerebral vasospasm.
AB  - Platelet-derived growth factor beta (PDGFbeta) has been proposed to contribute to
      the development of cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH),
      and soluble PDGFRbeta (sPDGFRbeta) is considered to be an inhibitor of PDGF
      signaling. We aimed at determining the sPDGFRbeta concentrations in the
      cerebrospinal fluid (CSF) of patients with aneurysmal SAH (aSAH) and analyzing
      the relationship between sPDGFRbeta level and CVS. CSF was sampled from 32
      patients who suffered aSAH and five normal controls. Enzyme-linked immunosorbent
      assay was performed to determine the sPDGFRbeta concentrations in the CSF.
      Functional outcome was assessed using modified Rankin scale (mRS) at 6 months
      after aSAH. CVS was identified using transcranial Doppler or angio-CT or DSA. The
      cutoff of sPDGFRbeta for CVS was defined on the ROC curve. The concentrations of
      sPDGFRbeta following aSAH were both higher than those of normal controls on days
      1-3 and 4-6, and peaked on days 7-9 post-SAH. The cutoff value of sPDGFRbeta
      level on days 1-3 for CVS was defined as 975.38 pg/ml according to the ROC curve
      (AUC = 0.680, p = 0.082). In addition, CSF sPDGFRbeta concentrations correlated
      with CVS (r = 0.416, p = 0.018), and multivariate analysis indicated that
      sPDGFRbeta level higher than 975.38 pg/ml on days 1-3 was an independent
      predictor of CVS (p = 0.001, OR = 19.22, 95% CI: 3.27-113.03), but not for
      unfavorable outcome after aSAH in the current study. CSF sPDGFRbeta level
      increases after aSAH and is higher in patients who developed CVS, and sPDGFRbeta
      level higher than 975.38 pg/ml on days 1-3 is a potential predictor for CVS after
      SAH.

PMID- 29637449
TI  - Healthcare resources utilisation in primary progressive multiple sclerosis.
AB  - Epidemiological data on primary progressive multiple sclerosis (PPMS) are scarce.
      This study was aimed to evaluate the burden of PPMS in Italy with healthcare
      resources utilisation and costs for Italian National Health System (INHS). A 2
      year cross-sectional analysis of real-world data collected in the ARCO database,
      covering > 10 million Italian inhabitants, was performed. From a cohort of
      patients affected by MS in 2014, those supposedly affected by PPMS were defined
      by the concurrent matching of absence of disease-modifying treatments and use of
      rehabilitation services. Any other drug prescriptions, outpatient services and
      hospitalisations were analysed in 2015 for each subject. The average annual cost
      per patient was provided both for each expenditure item and by integrating these.
      Of 13,253,591 inhabitants, 18,453 resulted affected by MS (prevalence 139 *
      100,000). Of these, 1849 agreed with additional criteria to identify PPMS (10% of
      MS population). The 26.8% of these experienced at least one admission in 1 year,
      97.3% used at least one outpatient service and 94.3% received at least one
      reimbursed drug. In the perspective of INHS, PPMS generated an average annual
      cost of ? 3783 per person: 49% for hospitalisations, 28% for outpatient services
      and 23% for drugs. This study provides a reliable estimation of the PPMS burden
      in Italy, in terms of healthcare utilisation and direct costs. These findings
      could be useful to estimate the changes in health expenditure following the
      incoming of new drugs to treat PPMS with increase of pharmaceutical cost and
      potential decrease of rehabilitation and hospitalisation costs.

PMID- 29637451
TI  - Unilateral hyperhidrosis as persistently isolated feature of syringomyelia and
      Arnold Chiari type 1.

PMID- 29637450
TI  - The association of NF2 (neurofibromin 2) gene polymorphism and the risk of
      medulloblastomas.
AB  - To explore the relationship between NF2 promoter gene mutation and the risk of
      medulloblastomas (MBs). We collected tissues from 16 MB patients and 7 age
      matched non-MB controls. Gene sequencing, qPCR (real-time quantitative polymerase
      chain reaction), IHC (immunohistochemistry), and WB (Western blot) were used to
      analyze the changes in the NF2 gene sequence and expression between patients and
      controls. We found that NF2 promoter gene mutations occurred in MB patients. The
      NF2 mRNA expression was higher in the controls than in patients (p = 0.03 <
      0.05); however, the results of IHC and WB demonstrated that the NF2 protein
      expression was significantly higher in patients than in the controls (IHC: p =
      0.0001; WB: p = 0.01). There was no significant difference in the CRL4 mRNA and
      protein levels. In addition, NF2 protein was mainly expressed in the nucleus in
      MB patients, while the NF2 protein was mainly expressed in the cytoplasm in the
      controls. NF2 promoter mutations exist in MB patients. NF2 mRNA expression was
      higher in controls than patients; whereas NF2 protein level was higher in
      patients than in controls.

PMID- 29637452
TI  - C-S Bond Activation.
AB  - This review first briefly summarizes stoichiometric C-S bond activation by
      transition metal complexes and then focuses on catalytic synthetic reactions
      involving C-S bond activation.

PMID- 29637455
TI  - Leaching of metals from end-of-life solar cells.
AB  - The issue of recycling waste solar cells is critical with regard to the expanded
      use of these cells, which increases waste production. Technology establishment
      for this recycling process is essential with respect to the valuable and
      hazardous metals present therein. In the present study, the leaching potentials
      of Acidithiobacillus thiooxidans, Acidithiobacillus ferrooxidans, Penicillium
      chrysogenum, and Penicillium simplicissimum were assessed for the recovery of
      metals from spent solar cells, with a focus on retrieval of the valuable metal
      Te. Batch experiments were performed to explore and compare the metal removal
      efficiencies of the aforementioned microorganisms using spent media. P.
      chrysogenum spent medium was found to be most effective, recovering 100% of B,
      Mg, Si, V, Ni, Zn, and Sr along with 93% of Te at 30  degrees C, 150 rpm and 1%
      (w/v) pulp density. Further optimization of the process parameters increased the
      leaching efficiency, and 100% of Te was recovered at the optimum conditions of 20
      degrees C, 200 rpm shaking speed and 1% (w/v) pulp density. In addition, the
      recovery of aluminum increased from 31 to 89% upon process optimization. Thus,
      the process has considerable potential for metal recovery and is environmentally
      beneficial.

PMID- 29637454
TI  - Application of vermiculite-derived sustainable adsorbents for removal of
      venlafaxine.
AB  - Removal of emerging pollutants, such as pharmaceuticals, from wastewater is a
      challenge. Adsorption is a simple and efficient process that can be applied.
      Clays, which are natural and low-cost materials, have been investigated as
      adsorbent. In this work, raw vermiculite and its three modified forms (expanded,
      base, and acid/base treated) were tested for removal of a widely used
      antidepressant, venlafaxine. Adsorption kinetics followed Elovich's model for raw
      vermiculite while the pseudo-2nd order model was a better fit in the case of
      other materials. Equilibrium followed Langmuir's model for the raw and the
      acid/base-treated vermiculite, while Redlich-Peterson's model fitted better the
      expanded and the base-treated materials. The adsorption capacity of vermiculite
      was significantly influenced by the changes in the physical and chemical
      properties of the materials caused by the treatments. The base-treated, raw, and
      expanded vermiculites showed lower maximum adsorption capacities (i.e., 6.3 +/-
      0.5, 5.8 +/- 0.7, 3.9 +/- 0.2 mg g-1, respectively) than the acid/base-treated
      material (33 +/- 4 mg g-1). The acid/base-treated vermiculite exhibited good
      properties as a potential adsorbent for tertiary treatment of wastewater in
      treatment plants, in particular for cationic species as venlafaxine due to
      facilitation of diffusion of the species to the interlayer gallery upon such
      treatment. Graphical abstract ?.

PMID- 29637453
TI  - Exploring Wellness Interventions in Progressive Multiple Sclerosis: an Evidence
      Based Review.
AB  - PURPOSE OF REVIEW: There has been recent interest in the role of lifestyle and
      wellness-based approaches in the treatment and management of multiple sclerosis
      (MS). These approaches may be particularly relevant for patients with progressive
      MS, considering limited therapeutic options currently available. The purpose of
      this review is to examine the role of wellness-based interventions including
      exercise training, emotional well-being therapies, and dietary modification in
      patients with progressive MS. RECENT FINDINGS: We conducted a literature search
      on the efficacy of wellness-based interventions in patients with progressive MS
      published between 1985 and July 2017. The level of evidence for each trial was
      evaluated using the American Academy of Neurology criteria. Overall, 21 articles
      reporting on 16 wellness-based interventions were identified: ten trials involved
      exercise training, three involved emotional wellness therapies, two involved
      dietary modification, and one was a combined wellness intervention. There is
      level C evidence (possibly effective; one class II study) for the efficacy of
      aerobic exercise training on cardiorespiratory fitness in patients with
      progressive MS. There is level B evidence (probably effective; one class I study)
      for the efficacy of mindfulness training on psychological distress, depression,
      anxiety, pain, and quality of life in patients with progressive MS. There is
      inadequate evidence (level U) for efficacy of dietary modification (one class III
      study and one class IV study) and combined wellness interventions involving
      exercise training, meditation, and dietary modification (one class IV study).
      High-quality research is needed to provide evidence-based recommendations for
      wellness behaviors and lifestyle change in patients with progressive MS.

PMID- 29637456
TI  - Relations Between Psychosocial Job Characteristics and Work Ability in Employees
      with Chronic Headaches.
AB  - Purpose The aim of the study was to determine (a) to which extent job demands and
      job resources predict work ability in employees with chronic headaches, and (b)
      whether work ability in these employees is more hampered by high demands and more
      enhanced by resources than in employees without chronic disease. Methods All
      employees with chronic headaches (n = 593) and without chronic disease (n =
      13,742) were selected from The Netherlands Working Conditions Survey conducted in
      2013. This survey assessed amongst others job characteristics and various
      indicators of work ability, i.e. sick leave, employability, work engagement, and
      emotional exhaustion. Hierarchical regression analyses were conducted for
      employees with chronic headaches and compared to employees without chronic
      disease, controlling for age, gender and educational level. Results In employees
      with chronic headaches higher quantitative and emotional demands contributed to
      higher emotional exhaustion, and higher emotional demands to higher sick leave.
      Higher cognitive demands were however associated with higher work engagement.
      Higher autonomy was related to higher employability and lower emotional
      exhaustion. Higher supervisor and colleague support was associated with higher
      employability, higher engagement and lower emotional exhaustion. Higher
      supervisor support was associated with lower sick leave. Supervisor support
      emerged as a stronger predictor for emotional exhaustion in the employees with
      chronic headaches than in the employees without chronic disease. Conclusions Job
      demands and job resources are important for work ability in employees with
      chronic headaches. Furthermore, results suggest that these employees benefit more
      strongly from supervisor support than employees without chronic disease.

PMID- 29637457
TI  - Characterization of children hospitalized with traumatic brain injuries after
      building falls.
AB  - BACKGROUND: Unintentional falls cause a substantial proportion of pediatric
      traumatic brain injury (TBI), with building falls carrying particularly high risk
      for morbidity and mortality. The cohort of children sustaining building fall
      related TBI has not been well-examined. We sought to characterize children
      hospitalized with building fall-related TBIs and evaluate if specific factors
      distinguished these children from children hospitalized with TBI due to other
      fall mechanisms. We secondarily assessed if TBI severity among children injured
      due to a building fall varied between children from urban versus non-urban areas.
      METHODS: This was a secondary analysis of the Pediatric Health Information System
      (PHIS), an administrative database from pediatric hospitals. We identified
      children < 15 years old, hospitalized between 2009 and 2014, with an associated
      TBI-related diagnosis due to a fall as determined by International Classification
      of Diseases, Clinical Modification, Ninth revision (ICD9-CM) diagnosis codes.
      Urban versus non-urban status was determined using PHIS-assigned Rural-Urban
      Commuting Area codes. Injury severity (i.e. Injury Severity Score (ISS) and head
      Abbreviated Injury Scale (AIS) score) were calculated. Head AIS scores were
      dichotomized into minor/moderate (1-2) and serious/severe (3-6) for analysis.
      Frequencies, descriptive statistics, Chi-square analysis, and Mann-Whitney U
      analysis characterized populations and determined group differences. RESULTS: The
      study cohort included 23,813 children, of whom 933 (3.9%) fell from buildings.
      Within the building fall cohort, 707 (75.8%) resided in urban areas, 619 (66.3%)
      were male, 513 (55.0%) were white, and 528 (56.6%) had government insurance; the
      mean age was 3.8 years (SD 2.9). There was a larger proportion of children with
      serious/severe TBI among those injured from building falls relative to other
      falls (63.4% vs 53.9%, p <  0.01). Among children injured from building falls,
      those from non-urban areas were more likely to sustain a serious/severe TBI
      relative to urban children (58.9% vs 53.6%, p <  0.01). CONCLUSIONS: Children
      hospitalized following buildings falls with TBI sustained more severe injuries
      relative to other fall types. Although a majority of children hospitalized with
      building fall related-TBIs were from urban areas, those from non-urban areas
      frequently sustained serious head injuries. Future research should target
      expanding prevention efforts to include non-urban areas.

PMID- 29637458
TI  - Correction to: Plasma alpha-tocopherol determined by HPLC in dogs at different
      stages of chronic kidney disease: a retrospective study.
AB  - The above article originally published with an error present in the article
      title, "Plasma alpha-tochopherol determined by HPLC in dogs at different stages
      of chronic kidney disease: a retrospective study" this should instead have read,
      "Plasma alpha-tocopherol determined by HPLC in dogs at different stages of
      chronic kidney disease: a retrospective study" [bold text used to highlight
      problem area].

PMID- 29637459
TI  - Safety and Efficacy of Teneligliptin in Patients with Type 2 Diabetes Mellitus
      and Impaired Renal Function: Interim Report from Post-marketing Surveillance.
AB  - INTRODUCTION: Teneligliptin is a novel oral dipeptidyl peptidase-4 inhibitor for
      the treatment of type 2 diabetes mellitus (T2DM). Safety and efficacy of
      teneligliptin have been demonstrated in clinical studies; however, data
      supporting its use in patients with moderate or severe renal impairment are
      limited. This interim analysis of a post-marketing surveillance of teneligliptin,
      exploRing the long-term efficacy and safety included cardiovascUlar events in
      patients with type 2 diaBetes treated bY teneligliptin in the real-world (RUBY),
      aims to verify the long-term safety and efficacy of teneligliptin in Japanese
      patients with T2DM and impaired renal function. METHODS: For this analysis, we
      used the data from case report forms of the RUBY surveillance between May 2013
      and June 2017. The patients were classified into G1-G5 stages of chronic kidney
      disease according to estimated glomerular filtration rate (eGFR) at initiation of
      teneligliptin treatment. Safety and efficacy were evaluated in these subgroups.
      Patients on dialysis were also assessed. Safety was assessed from adverse drug
      reactions (ADRs). Glycemic control was evaluated up to 2 years after
      teneligliptin initiation. RESULTS: A total of 11,677 patients were enrolled in
      the surveillance and 11,425 patient case-report forms were collected for the
      interim analysis. The incidence of ADRs in each subgroup was 2.98-6.98% of
      patients, with no differences in the ADR profile (including hypoglycemia and
      renal function ADRs) between subgroups. At 1 and 2 years after starting
      teneligliptin, the least-squares mean change in HbA1c adjusted to the baseline
      was - 0.68 to - 0.85% and - 0.71 to - 0.85% across the eGFR groups, respectively.
      Treatment with teneligliptin in patients on dialysis reduced or tended to reduce
      glycated albumin levels [- 2.29%, (p < 0.001) after 1 year; - 1.64%, (p = 0.064)
      after 2 years]. CONCLUSIONS: During long-term treatment, teneligliptin was
      generally well tolerated in patients with any stage of renal impairment from
      normal to end-stage renal disease, including those on dialysis, and improved
      glycemic control. TRIAL REGISTRATION NUMBER: Japic CTI-153047. FUNDING:
      Mitsubishi Tanabe Pharma Corporation and Daiichi Sankyo Co, Ltd.

PMID- 29637460
TI  - Author Correction: Liraglutide Improves Cardiovascular Risk as an Add-on to
      Metformin and Not to Insulin Secretagogues in Type 2 Diabetic Patients: A Real
      life 48-Month Retrospective Study.
AB  - Author Correction to: Diabetes Ther (2018) 9:363-371.

PMID- 29637461
TI  - Biomarkers for Diagnosing Ventilator Associated Pneumonia: Is that the Way
      Forward?

PMID- 29637462
TI  - Severe Dengue: Developing a Universally Applicable Simple Prediction Model.

PMID- 29637464
TI  - Celiac Disease in Association with Gilbert's Syndrome.

PMID- 29637465
TI  - Why kidneys fail post-partum: a tubulocentric viewpoint.
AB  - Kidneys may fail post-partum in a number of circumstances due, for example, to
      post-partum haemorrhage, preeclampsia, amniotic fluid embolism or septic
      abortion. All these conditions in pregnancy and post partum represent a threat
      not only to the endothelium but also to the renal tubular epithelium, and as such
      may lead to rapid and also irreversible impairment of the renal function. This
      paper is a non-systematic review of the literature and of our experience, in
      which we discuss the main open issues on kidney disease in pregnancy and
      following delivery, in particular as regards tubular damage, with the aim to help
      reasoning on acute kidney injury (AKI) following delivery. The review will
      emphasize the often under-estimated importance of the tubular epithelium in the
      peri-partum period and will: (1) describe the main characteristics of the renal
      tissues around delivery; (2) define pregnancy-related AKI according to recent
      Kidney Disease/Improving Global Outcome (KDIGO) guidelines; (3) discuss the most
      common circumstances of post-partum AKI; and (4) describe the input expected from
      urinalysis, renal imaging and kidney biopsy.

PMID- 29637466
TI  - Long-Term Outcomes of Unlocking Chinese Patients with Severe Mental Illness.
AB  - In 2006, the "unlocking program" was implemented in Hebei province, China to
      promote the human rights for people with severe mental illness who were
      physically restrained at home. We assessed the long term outcomes of the
      "unlocking program" following the provision of hospital and community psychiatric
      care over 10 years and explored their associated factors. A total of 107 patients
      with severe mental illness who were "unlocked" in the program were included.
      Outcome measures were collected with standardized rating scales at 2 separate
      time points in August 2012 and November 2016. Poor outcome was defined either as
      being relocked, or missing to follow up or death. In 2012, 36 patients (33.6%)
      had poor outcomes. Poor outcome was positively associated with follow-up length
      and less caregiver burden at baseline. By 2016, 53 patients (49.5%) were found to
      have poor outcomes. There was only a trend of positive association between poor
      outcome and less caregiver burden at baseline. Poor long-term outcomes were
      common in patients with severe mental illness following the "unlocking program".
      Evidence-based treatment strategies and mental health services to improve the
      outcomes and protect the human rights of patients subjected to being locked in
      the community are urgently needed.

PMID- 29637467
TI  - A cross-modal effect of noise: the disappearance of the alarm reaction of a
      freshwater fish.
AB  - Anthropogenic noise pollution is recognized as a major global stressor of
      animals. While many studies have assessed the unimodal impacts of noise pollution
      with a focus on intraspecific acoustic communication, little is known about noise
      pollution on the perception of visual and chemical information. The 'distracted
      prey hypothesis' posits that processing noise interferes with processing other
      information in the brain. Here, we found evidence for such a cross-modal effect
      of noise on the antipredator behaviour of a freshwater prey fish, the fathead
      minnow, Pimephales promelas. In laboratory trials, exposure to noise from a
      motorboat caused the total absence of the classical fright reaction of minnows to
      conspecific alarm cues, whereas an ambient noise control had no such impact. In
      natural habitats, the impairment of such antipredator behaviour due to noise
      pollution could have major fitness consequences. We discuss how our findings
      translate to animal ecology and the need for future studies that target specific
      management decisions regarding noise pollution.

PMID- 29637469
TI  - Correction to: Palivizumab Prophylaxis Against Respiratory Syncytial Virus
      Infection in Children with Immunocompromised Conditions or Down Syndrome: A
      Multicenter, Post-Marketing Surveillance in Japan.
AB  - "Newborns, infants, or young children aged 24 months and under who have Down
      syndrome, and children <= 24 months of age without a current hs-CHD if they had
      experienced persistent respiratory symptoms or regular outpatient treatment due
      to a respiratory tract infection in previous RSV seasons were also eligible for
      the study."

PMID- 29637468
TI  - Tissue Distribution and Gender-Specific Protein Expression of Cytochrome P450 in
      five Mouse Genotypes with a Background of FVB.
AB  - PURPOSE: To systematically investigate tissue distribution and gender-specific
      protein expression of Cytochrome P450 (Cyps) in five mouse genotypes with a
      background of Friend virus B (FVB). METHODS: The Cyps were extracted from the
      tissue S9 fractions of the main metabolic organs and then absolutely quantified
      by applying the UHPLC-MS/MS method. RESULTS: The liver had the highest expression
      of Cyps, followed by the small intestine and kidney. In the liver, Cyp1a2,
      Cyp2c29, Cyp2c39, Cyp2d22, Cyp2e1, and Cyp3a11 were the main isoforms. Cyp1a2 and
      Cyp2c29 were male-specific, while Cyp2c39 was female-specific. Compared with the
      expression in Wild-type (WT) FVB mice, the expression of Cyp1a2, Cyp1b1, Cyp2d22,
      and Cyp3a25 significantly decreased in female efflux transporter (ET) knockout
      mice. In the small intestine, Cyp2c29 and Cyp3a11 were the major isoforms.
      Knockout of ET didn't alter the expression levels of most Cyps. However, female
      ET knockout mice presented higher Cyp2c29 expression than WT FVB mice. The Cyp7a1
      expression was markedly decreased in ET knockout mice except Bcrp1-/- mice. In
      the kidney, Cyp2e1 was the main isoform and exhibited male specificity. Knockout
      of ET slightly affected the protein expression of Cyps in the brain, heart, lung,
      spleen and stomach. CONCLUSIONS: A comprehensive understanding of the
      distribution characteristics and gender-specific expression of Cyps in major
      metabolic organs of WT and ET knockout FVB mice should contribute to a better
      understanding of drug efficacy and toxicity, and drug-drug interactions.

PMID- 29637470
TI  - Anticoagulation Management After Transcatheter and Surgical Valve Replacement.
AB  - Valvular heart disease is associated with high morbidity and mortality, and its
      prevalence is rising as the population ages. Treatment of severe valvular disease
      has historically required surgical correction, which carries its own risks, but
      there have been significant advances in valve replacement technologies and
      techniques, most notably the development of percutaneous options for repair and
      replacement. While valve replacements alleviate the hemodynamic burden of
      valvular disease, the synthetic material comprising part or all of the
      replacement valve provides nidus for clot, necessitating antithrombotic therapy.
      Providing the right balance between thromboembolic and bleeding risk is made more
      challenging by the comorbidities that often co-exist with valve disease in the
      elderly patient. The backbone of anticoagulation regimens has been comprised of
      aspirin, warfarin, or both, but newer agents are gaining popularity due to
      improved convenience and safety profiles. The expanding medical arsenal brings
      not only more options but also more complexity with the increasing number of
      possible combinations of anticoagulants and valve types. In general, mechanical
      heart valves are thought to be the most durable option with the highest
      thrombotic risk, requiring anticoagulation with warfarin with the addition of
      aspirin. Bioprosthetic valves placed surgically or percutaneously are less likely
      to cause thrombus and have been successfully managed with antiplatelet agents
      alone. However, concerns about previously undetected complications coming to
      light with new imaging techniques have brought uncertainty about current
      practice. In order to provide optimal care for our patients, careful review of
      the current literature, guideline recommendations, and the thrombotic and
      bleeding risk unique to the individual patient and valve type is necessary.

PMID- 29637471
TI  - A multi-arm phase I dose escalating study of an oral NOTCH inhibitor BMS-986115
      in patients with advanced solid tumours.
AB  - Background Inhibiting Notch is a promising anti-cancer strategy as it plays a
      critical role in cancer stem cells maintenance and tumour angiogenesis. BMS
      986115 is an orally active, selective inhibitor of gamma-secretase mediated Notch
      signalling. Method Two dose escalation schedules (Arm-A continuous daily schedule
      and Arm-B intermittent 2 times weekly schedule) of BMS-986115 were evaluated in
      advanced solid tumour patients. The primary objective was to establish the
      safety, tolerability and Maximum Tolerated Dose (MTD) of BMS-986115. Results
      Thirty six patients (24 in Arm A and 12 in Arm B) were treated. The most frequent
      treatment related adverse advents were diarrhoea (72%), hypophosphataemia (64%),
      and nausea (61%). The MTD was 1.5 mg daily in Arm A but not established in Arm B.
      Four patients in Arm A and 2 in Arm B experienced dose limiting toxicities (grade
      3 nausea, diarrhoea, pruritus/urticaria and ileus). BMS-986115 showed dose
      related increase in exposure within the dose range tested. Target inhibition of
      Notch pathway related genes was observed. Three patients in Arm A and 2 in Arm B
      achieved stable disease for more than 6 months. Conclusion The daily oral dosing
      of BMS-986115 is safe and tolerable with biological activity demonstrated by
      continuous target engagement and Notch signalling inhibition.

PMID- 29637473
TI  - Ecosystem service flows from a migratory species: Spatial subsidies of the
      northern pintail.
AB  - Migratory species provide important benefits to society, but their cross-border
      conservation poses serious challenges. By quantifying the economic value of
      ecosystem services (ESs) provided across a species' range and ecological data on
      a species' habitat dependence, we estimate spatial subsidies-how different
      regions support ESs provided by a species across its range. We illustrate this
      method for migratory northern pintail ducks in North America. Pintails support
      over $101 million USD annually in recreational hunting and viewing and
      subsistence hunting in the U.S. and Canada. Pintail breeding regions provide
      nearly $30 million in subsidies to wintering regions, with the "Prairie Pothole"
      region supplying over $24 million in annual benefits to other regions. This
      information can be used to inform conservation funding allocation among migratory
      regions and nations on which the pintail depends. We thus illustrate a
      transferrable method to quantify migratory species-derived ESs and provide
      information to aid in their transboundary conservation.

PMID- 29637472
TI  - Curating viscoelastic properties of icosahedral viruses, virus-based
      nanomaterials, and protein cages.
AB  - The beauty, symmetry, and functionality of icosahedral virus capsids has
      attracted the attention of biologists, physicists, and mathematicians ever since
      they were first observed. Viruses and protein cages assemble into functional
      architectures in a range of sizes, shapes, and symmetries. To fulfill their
      biological roles, these structures must self-assemble, resist stress, and are
      often dynamic. The increasing use of icosahedral capsids and cages in materials
      science has driven the need to quantify them in terms of structural properties
      such as rigidity, stiffness, and viscoelasticity. In this study, we employed
      Quartz Crystal Microbalance with Dissipation technology (QCM-D) to characterize
      and compare the mechanical rigidity of different protein cages and viruses. We
      attempted to unveil the relationships between rigidity, radius, shell thickness,
      and triangulation number. We show that the rigidity and triangulation numbers are
      inversely related to each other and the comparison of rigidity and radius also
      follows the same trend. Our results suggest that subunit orientation, protein
      protein interactions, and protein-nucleic acid interactions are important for the
      resistance to deformation of these complexes, however, the relationships are
      complex and need to be explored further. The QCM-D based viscoelastic
      measurements presented here help us elucidate these relationships and show the
      future prospect of this technique in the field of physical virology and nano
      biotechnology.

PMID- 29637474
TI  - Short-term outcome of carotid dissecting pseudoaneurysm: is it always benign?

PMID- 29637475
TI  - Building a Culture of Excellence in Cancer Education: a Message from Your
      President.

PMID- 29637477
TI  - Real-world management of heart failure in the Netherlands : Improving quality of
      care by simple measures.

PMID- 29637476
TI  - A Meta-analysis of Arsenic Exposure and Lung Function: Is There Evidence of
      Restrictive or Obstructive Lung Disease?
AB  - PURPOSE OF REVIEW: Hundreds of millions of people worldwide are exposed to
      arsenic via contaminated water. The goal of this study was to identify whether
      arsenic-associated lung function deficits resemble obstructive- or restrictive
      like lung disease, in order to help illuminate a mechanistic pathway and identify
      at-risk populations. RECENT FINDINGS: We recently published a qualitative
      systematic review outlining the body of research on arsenic and non-malignant
      respiratory outcomes. Evidence from several populations, at different life
      stages, and at different levels of exposure showed consistent associations of
      arsenic exposure with chronic lung disease mortality, respiratory symptoms, and
      lower lung function levels. The published review, however, only conducted a broad
      qualitative description of the published studies without considering specific
      spirometry patterns, without conducting a meta-analysis, and without evaluating
      the dose-response relationship. We searched PubMed and Embase for studies on
      environmental arsenic exposure and lung function. We performed a meta-analysis
      using inverse-variance-weighted random effects models to summarize adjusted
      effect estimates for arsenic and forced expiratory volume in one second (FEV1),
      forced vital capacity (FVC), and FEV1/FVC ratio. Across nine studies, median
      water arsenic levels ranged from 23 to 860 MUg/L. The pooled estimated mean
      difference (MD) comparing the highest category of arsenic exposure (ranging from
      > 11 to > 800 MUg/L) versus the lowest (ranging from < 10 to < 100 MUg/L) for
      each study for FEV1 was - 42 mL (95% confidence interval (CI) - 70, - 16) and for
      FVC was - 50 mL (95% CI - 63, - 37). Three studies reported effect estimates for
      FEV1/FVC, for which there was no evidence of an association; the pooled estimated
      MD was 0.01 (95% CI - 0.005, 0.024). This review supports that arsenic is
      associated with restrictive impairments based on inverse associations between
      arsenic and FEV1 and FVC, but not with FEV1/FVC. Future studies should confirm
      whether low-level arsenic exposure is a restrictive lung disease risk factor in
      order to identify at-risk populations in the USA.

PMID- 29637478
TI  - Overcoming Tumor-Induced Immune Suppression: From Relieving Inhibition to
      Providing Costimulation with T Cell Agonists.
AB  - Recent advancements in T-cell biology and antibody engineering have opened doors
      to significant improvements in cancer immunotherapy. Initial success with
      monoclonal antibodies targeting key receptors that inhibit T-cell function such
      as cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed death-ligand 1 (PD-1)
      have demonstrated the potency of this new class of therapy, highlighted by long
      term complete responses for metastatic cancers once thought incurable. However,
      only a subset of patients responds to checkpoint blockade because of a multitude
      of factors, including an immunosuppressive tumor microenvironment and the
      mutational burden of the cancer. Novel antibodies, as well as ligand
      immunoglobulin fusion proteins that target costimulatory immune receptors, are
      being developed and tested in clinical trials to further enhance the anti-tumor
      immune response. Many of these costimulatory receptors are in the tumor necrosis
      factor receptor superfamily (TNFRSF) and are expressed on multiple immune cell
      types, including inhibitory cells. While TNFRSFs signal through common pathways,
      the outcome of targeting different receptors depends on the functional status of
      the cell types expressing the relevant receptors. In this review, we discuss the
      current state of targeted costimulatory immunotherapy.

PMID- 29637479
TI  - A quality improvement program in pediatric practices to increase tailored injury
      prevention counseling and assess self-reported changes made by families.
AB  - BACKGROUND: Many pediatric providers struggle to screen families for the majority
      of age-appropriate injury risks and educate them when appropriate. Standardized
      tools have helped physicians provide effective, more purposeful counseling. In
      this study, pediatricians utilized a standardized, injury prevention screening
      tool to increase targeted discussions and families were re-screened at subsequent
      visits to determine changes in their behavior. METHODS: Pediatric practices,
      recruited from the Ohio Chapter, American Academy of Pediatrics database, self
      selected to participate in a quality improvement program. Two screening tools,
      for children birth-4 month and 6-12 month, with corresponding talking points,
      were to be implemented into every well child visit. During the 7-month
      collaborative, screening results and pediatrician counseling for reported unsafe
      behaviors were calculated. Patients who completed a screening tool at subsequent
      visits were followed up at a later visit to determine self-reported behavior
      changes. We examined statistically significant differences in frequencies using
      the X2 test. Providers received maintenance of certification IV credit for
      participation. RESULTS: Seven practices (39 providers) participated. By the
      second month, participating providers discussed 75% of all inappropriate
      responses for birth-4 month screenings and 87% for 6-12 months. Of the 386
      families who received specific counseling and had a follow-up visit, 65% (n =
      94/144) of birth-4 month and 65% (n = 59/91) of 6-12 month families made at least
      one behavior change. The X2 test showed that families who received counseling
      versus those that did not were significantly more likely to change inappropriate
      behaviors (p < 0.05). Overall, of all the risks identified, 45% (136) of birth-4
      month and 42% (91) of 6-12 month behaviors reportedly changed after a
      practitioner addressed the topic area. CONCLUSIONS: Participation in a quality
      improvement program within pediatric offices can increase screening for injury
      risks and encourage tailored injury prevention discussions during an office
      encounter. As a result, significantly more families reported to practice safer
      behaviors at later visits.

PMID- 29637481
TI  - Dermoscopy of Concerning Pigmented Lesions and Primary Care Providers' Referrals
      at Intervals After Randomized Trial of Mastery Learning.

PMID- 29637480
TI  - Quality and Correlates of Peer Relationships in Youths with Chronic Pain.
AB  - Youths with chronic pain may experience difficulties with peer relationships. We
      investigated the quality and correlates of peer relationships in a sample of 181
      youths with chronic pain. A majority of youths were satisfied with their
      relationships with peers; however, levels were highly variable. Higher functional
      impairment and depression levels predicted lower peer relationship quality,
      controlling for demographic and other pain-related factors. In addition, peer
      relationship quality and pain severity predicted child depression and anxiety
      symptoms, whereas peer relationship quality only predicted anger symptoms.
      Relationship quality moderated the association between pain severity and
      functional impairment, suggesting that strong relationships with peers may buffer
      the effects of pain on functioning. Peer relationships seem particularly
      important for the adjustment and psychological well-being of youths with chronic
      pain. Particular attention should be given to functionally impaired and depressed
      children, who may be at higher risk of peer difficulties.

PMID- 29637482
TI  - Antiviral prophylaxis for preventing reactivation of hepatitis B virus in
      rheumatic patients: a systematic review and meta-analysis.
AB  - To estimate the risk of reactivation of hepatitis B virus (HBV) and evaluate the
      effectiveness of antiviral prophylaxis (AVP) in patients with different status of
      HBV infection undergoing antirheumatic therapies. We searched Cochrane Library,
      Medline, and EMBASE for randomized controlled trials (RCTs), quasi-RCTs, non
      RCTs, cohort studies, or case series studies examining reactivation of HBV in
      patients undergoing antirheumatic therapy with or without AVP. We estimated the
      HBV reactivation rate (HRR) and its 95% confidence interval (CI) among different
      patient groups (indirect comparison). We also calculated rate ratio (RR), rate
      difference (RD) with their 95% CIs, and the number needed to treat (NNT) of AVP
      (direct comparison). Fifty-three case series studies with 2162 patients were
      included. The RD of AVP was - 0.13 (95% CI - 0.21 to - 0.05) for all patients, -
      0.16 (95% CI - 0.26 to - 0.06) for rheumatic patients with chronic HBV infection,
      but not statistically significant for patients with other status of HBV
      infection. Lamivudine (RD - 0.10, 95% CI - 0.25 to 0.05) was less effective than
      other prophylactic antiviral drugs (RD - 0.31, 95% CI - 0.52 to - 0.11). The HHR
      varied from 55 to 5% by HBV status and treatment. There is limited evidence that
      AVP was effective for preventing reactivation of HBV in patients undergoing
      antirheumatic therapy. The effectiveness varies by patient HBV status and
      antiviral regimens. Rheumatic HBV carriers may be more beneficial from AVP, and
      lamivudine may be inferior to other AVP regimens. Findings in this study warrant
      further investigation in rigorous RCTs.

PMID- 29637483
TI  - Evaluation of the comorbidity burden in patients with ankylosing spondylitis
      using a large US administrative claims data set.
AB  - Comorbidities among US patients with ankylosing spondylitis (AS) are inadequately
      understood. This study compared the prevalence and incidence of comorbidities
      between patients with AS and matched controls using national claims databases.
      Adults enrolled in the MarketScan Commercial and Medicare databases with >= 1
      inpatient or >= 2 non-rule-out outpatient diagnoses of AS between January 1, 2012
      and December 31, 2014 were included. Patients had to have >= 1 AS diagnosis in
      2013; the first AS diagnosis in 2013 was assigned as the index date. Control
      patients without AS were matched to AS patients on age, geographic region, index
      calendar year, and sex. Comorbidities were evaluated in AS patients and matched
      controls during the baseline and follow-up periods (before and after the index
      date, respectively). Hazard ratios of developing new comorbidities were estimated
      using Cox proportional hazard models adjusted for patients' characteristics. A
      total of 6679 patients with AS were matched to 19,951 control patients. In
      addition to extra-articular manifestations of AS (inflammatory bowel disease
      [IBD], psoriasis, uveitis), a higher proportion of AS patients had asthma,
      cardiovascular disease, depression, dyslipidemia, gastrointestinal ulcers,
      malignancies, multiple sclerosis, osteoporosis, sleep apnea, and spinal fractures
      during the baseline period than matched controls. After AS diagnosis, a higher
      proportion of patients developed newly diagnosed cases of cardiovascular
      diseases, depression, osteoporosis, spinal fracture, IBD, psoriasis, and uveitis
      than matched controls. In this real-world, US claims-based study, patients with
      AS were shown to have significantly more comorbidities than matched controls.

PMID- 29637484
TI  - Comparative evaluation of therapeutic efficacy of intra-articular oxaceprol with
      conventional modalities in osteoarthritis animal model.
AB  - The duration and dose-dependent side effects of conventional intra-articular
      corticosteroid treatment in osteoarthritis (OA) like cartilage damage and
      chondrocyte toxicity warrant the search for alternative therapeutics. Oxaceprol,
      a recognized oral therapeutic agent for osteoarthritis, is yet to be explored for
      its intra-articular route of administration confirming better safety profile. In
      this study, a comparative evaluation of intra-articular oxaceprol and
      corticosteroid is carried out in osteoarthritis rabbit model. Osteoarthritis was
      induced by monosodium iodoacetate in rabbits. After randomization into three
      groups of five animals each: OA with intra-articular injection of saline, OA with
      intra-articular injection of oxaceprol, and OA with intra-articular injection of
      corticosteroids, treatment efficacy was analyzed by evaluation of inflammation
      through knee swelling, pain assessment by wire walking, and hot plate method.
      Further biopsies were collected for histological characterization. Intra
      articular oxaceprol and corticosteroids reduced 20.5 and 24.5% knee swelling
      respectively within 4 weeks compared to those in control osteoarthritic rabbits.
      Oxaceprol exhibited analgesic action in visual analogue scoring of wire walking
      method. Hot plate test further confirmed drastic minimization of pain in
      oxaceprol intervention. Histological investigation suggested that application of
      oxaceprol has the abilities to protect articular cartilages from degenerative
      changes that occur in osteoarthritis. Marked improvement both in bone and
      cellular matrixes was observed in oxaceprol-treated group while gross lesions
      were visible and consisted of a well-demarcated area of cartilage erosion in
      control group. Intra-articular injection of oxaceprol showed remarkable
      improvement of articular cartilage in chemically induced osteoarthritic rabbits.

PMID- 29637485
TI  - The Effects of 'Face' on Listening Comprehension: Evidence from Advanced
      Jordanian Speakers of English.
AB  - This empirical study examines the extent to which 'face', i.e. (audio visual
      dialogues), affects the listening comprehension of advanced Jordanian EFL
      learners in a TOFEL-like test, as opposed to its absence (i.e. a purely audio
      test) which is the current norm in many English language proficiency tests,
      including but not limited to TOFEL iBT, TOEIC and academic IELTS. Through an
      online experiment, 60 Jordanian postgraduate linguistics and English literature
      students (advanced EFL learners) at the University of Jordan sit for two
      listening tests (simulating English proficiency tests); namely, one which is
      purely audio [i.e. without any face (including any visuals such as motion, as
      well as still pictures)], and one which is audiovisual/video. The results clearly
      show that the inclusion of visuals enhances subjects' performance in listening
      tests. It is concluded that since the aim of English proficiency tests such as
      TOEFL iBT is to qualify or disqualify subjects to work and study in western
      English-speaking countries, the exclusion of visuals is unfounded. In actuality,
      most natural interaction includes visibility of the interlocutors involved, and
      hence test takers who sit purely audio proficiency tests in English or any other
      language are placed at a disadvantage.

PMID- 29637486
TI  - A photon recycling approach to the denoising of ultra-low dose X-ray sequences.
AB  - PURPOSE: Clinical procedures that make use of fluoroscopy may expose patients as
      well as the clinical staff (throughout their career) to non-negligible doses of
      radiation. The potential consequences of such exposures fall under two
      categories, namely stochastic (mostly cancer) and deterministic risks (skin
      injury). According to the "as low as reasonably achievable" principle, the
      radiation dose can be lowered only if the necessary image quality can be
      maintained. METHODS: Our work improves upon the existing patch-based denoising
      algorithms by utilizing a more sophisticated noise model to exploit non-local
      self-similarity better and this in turn improves the performance of low-rank
      approximation. The novelty of the proposed approach lies in its properly designed
      and parameterized noise model and the elimination of initial estimates. This
      reduces the computational cost significantly. RESULTS: The algorithm has been
      evaluated on 500 clinical images (7 patients, 20 sequences, 3 clinical sites),
      taken at ultra-low dose levels, i.e. 50% of the standard low dose level, during
      electrophysiology procedures. An average improvement in the contrast-to-noise
      ratio (CNR) by a factor of around 3.5 has been found. This is associated with an
      image quality achieved at around 12 (square of 3.5) times the ultra-low dose
      level. Qualitative evaluation by X-ray image quality experts suggests that the
      method produces denoised images that comply with the required image quality
      criteria. CONCLUSION: The results are consistent with the number of patches used,
      and they demonstrate that it is possible to use motion estimation techniques and
      "recycle" photons from previous frames to improve the image quality of the
      current frame. Our results are comparable in terms of CNR to Video Block Matching
      3D-a state-of-the-art denoising method. But qualitative analysis by experts
      confirms that the denoised ultra-low dose X-ray images obtained using our method
      are more realistic with respect to appearance.

PMID- 29637487
TI  - Playground slide-related injuries in preschool children: increased risk of lower
      extremity injuries when riding on laps.
AB  - BACKGROUND: The purpose of this study was to better understand the factors
      associated with playground slide-related injuries in preschool children and to
      test the hypothesis that riding on laps increases the likelihood of lower
      extremity injuries. METHODS: Playground slide-related injuries (product code
      1242) in children <=5 years of age treated in emergency departments from 2002 to
      2015 were identified (N = 12,686) using the U.S. Consumer Product Safety
      Commission's National Electronic Injury Surveillance System (NEISS). Descriptive
      and comparative analyses, including chi-square testing and binary logistic
      regression, were performed. RESULTS: Based on NEISS stratified national sampling
      estimates, over 350,000 children <=5 years of age were injured on slides from
      2002 to 2015. Overall, 59% of the children were male, and 65% were white. Almost
      60% of injuries occurred in parks or other public areas. The most frequent
      diagnosis was a fracture (36%); lacerations were 19% of the injuries. A higher
      proportion of musculoskeletal injuries were seen in toddlers < 3 years old as
      compared to those 3-5 years of age (p < 0.001). Injuries to the lower extremities
      increased in frequency as age decreased, whereas injuries to the upper
      extremities and head/neck/face were more common in older preschoolers. Children <
      3 years of age were 12 times more likely to be identified from narratives as
      being on another person's lap at the time of injury. Children identified as being
      on a lap had an increased odds of injury to the lower extremity than to other
      body parts (OR 43.0, 95% confidence interval (CI) 32.0-58.0), and of lower
      leg/ankle fracture than fractures elsewhere (OR 49.5, 95% CI 31.7-77.4).
      CONCLUSIONS: Decreasing age was associated with a higher likelihood of being
      identified as sliding down on another person's lap and a higher likelihood of
      lower extremity injuries. Healthcare providers should be mindful of the potential
      for these slide-related injuries as they can result in a toddler's fracture of
      the tibia, which may be occult. Parents should also be made aware of this
      increased risk and counseled that a child's foot can catch on the slide's
      surfaces when going down on a person's lap with subsequent twisting forces that
      can result in a fracture.

PMID- 29637488
TI  - Improving the biopharmaceutical attributes of mangiferin using vitamin E-TPGS co
      loaded self-assembled phosholipidic nano-mixed micellar systems.
AB  - The current research work encompasses the development, characterization, and
      evaluation of self-assembled phospholipidic nano-mixed miceller system (SPNMS) of
      a poorly soluble BCS Class IV xanthone bioactive, mangiferin (Mgf) functionalized
      with co-delivery of vitamin E TPGS. Systematic optimization using I-optimal
      design yielded self-assembled phospholipidic nano-micelles with a particle size
      of < 60 nm and > 80% of drug release in 15 min. The cytotoxicity and cellular
      uptake studies performed using MCF-7 and MDA-MB-231 cell lines demonstrated
      greater kill and faster cellular uptake. The ex vivo intestinal permeability
      revealed higher lymphatic uptake, while in situ perfusion and in vivo
      pharmacokinetic studies indicated nearly 6.6- and 3.0-folds augmentation in
      permeability and bioavailability of Mgf. In a nutshell, vitamin E functionalized
      SPNMS of Mgf improved the biopharmaceutical performance of Mgf in rats for
      enhanced anticancer potency.

PMID- 29637489
TI  - Molecular characterization and expression profiling of BMP 3 gene in broiler and
      layer chicken.
AB  - A study was carried out to characterize and explore the expression profile of BMP
      3 gene in control broiler and control layer chicken. The total open reading frame
      of BMP 3 (1389 bp) was cloned and sequenced. The control broiler and control
      layer chicken showed variation at nucleotide and amino acid level with reference
      gene (Gallus gallus, NCBI Acc. No. NM_001034819). When compared to reference
      gene, the control broiler showed four nucleotide differences (c.192A>G, c.519C>T,
      903G>A and 960C>G), while, control layer showed variation at c.33G>C, 192A>G,
      858G>A, 904G>A, 960C>G and 1257C>T making six differences in total. However,
      between control broiler and control layer lines, nucleotide differences was
      observed at c.33G>C, 519T>C, 858G>A, 903A>G, 904G>A and 1257C>T. The change at
      amino acid level between reference and control broiler was p.D320N and with
      control layer chicken, it was p.D302N and p.D320N. On the other hand, a single
      amino acid difference (p.D302N) was observed between the control broiler and
      control layer chicken lines. The phylogenetic study displayed a close
      relationship between broiler and layer lines and reference gene and also with
      other avian species resulting in a cluster formation. These cluster in turn
      displayed a distant link with the mammalian species. The expression profile of
      BMP 3 gene exhibited a variation at different stages of embryonic development and
      also at post embryonic period among the lines with control layer showing higher
      expression than that of broiler chicken. The protein was also detected in bone
      marrow tissue of broiler and layer lines by western blotting. It is concluded
      that the BMP 3 gene sequence differed at nucleotide and amino acid level among
      the lines and the gene expressed differentially at different periods of embryonic
      development and also at post hatch period.

PMID- 29637491
TI  - The Chemical Basis of Species, Sex, and Individual Recognition Using Feces in the
      Domestic Cat.
AB  - Scents emitted from excretions provide important information about the owner.
      Volatile compounds with higher levels in a species and/or sex, or that vary among
      individuals could be odor cues for species and/or sex, or individual recognition.
      However, such compounds have been identified in only a few vertebrate species. In
      domestic cats (Felis silvestris catus), it is known that unburied cat feces are
      territorial markers asserting the border of their home range, but little was
      known which fecal compounds are scent cues for species, sex, and individual
      recognition in cats. In the present study, we demonstrated the chemical basis for
      species, sex, and individual recognition using feces of cats. For males, major
      contents were fatty acids and 3-mercapto-3-methyl-1-butanol (MMB), a derivative
      of the unusual amino acid, felinine. MMB emission levels from feces had sex-based
      differences (male > female) and dynamic temporal changes during aging. Cats
      distinguished fecal odors with and without MMB, and different fatty acid
      compositions among individuals. No cat-specific compound, such as MMB, was
      detectable from their anal odor emitting fatty acids. We concluded that fecal MMB
      is a male sex recognition pheromone in cats and also provides a temporal trace of
      the owner. After sensing MMB, they may distinguish individual differences of
      conspecific feces with variable subsets of fatty acids. In contrast to scent
      marks, since cats can obtain species information from visual cues before sniffing
      conspecific anal odors, they may use their efforts to distinguish individual
      differences of anal odors during sniffing.

PMID- 29637490
TI  - Chemical Ecology and Sociality in Aphids: Opportunities and Directions.
AB  - Aphids have long been recognized as good phytochemists. They are small sap
      feeding plant herbivores with complex life cycles that can involve cyclical
      parthenogenesis and seasonal host plant alternation, and most are plant
      specialists. Aphids have distinctive traits for identifying and exploiting their
      host plants, including the expression of polyphenisms, a form of discrete
      phenotypic plasticity characteristic of insects, but taken to extreme in aphids.
      In a relatively small number of species, a social polyphenism occurs, involving
      sub-adult "soldiers" that are behaviorally or morphologically specialized to
      defend their nestmates from predators. Soldiers are sterile in many species,
      constituting a form of eusociality and reproductive division of labor that bears
      striking resemblances with other social insects. Despite a wealth of knowledge
      about the chemical ecology of non-social aphids and their phytophagous
      lifestyles, the molecular and chemoecological mechanisms involved in social
      polyphenisms in aphids are poorly understood. We provide a brief primer on
      aspects of aphid life cycles and chemical ecology for the non-specialists, and an
      overview of the social biology of aphids, with special attention to
      chemoecological perspectives. We discuss some of our own efforts to characterize
      how host plant chemistry may shape social traits in aphids. As good
      phytochemists, social aphids provide a bridge between the study of insect social
      evolution sociality, and the chemical ecology of plant-insect interactions.
      Aphids provide many promising opportunities for the study of sociality in
      insects, and to understand both the convergent and novel traits that characterize
      complex sociality on plants.

PMID- 29637492
TI  - Oxidatively Active Plant Phenolics Detected by UHPLC-DAD-MS after Enzymatic and
      Alkaline Oxidation.
AB  - We developed a combination of methods to estimate the alkaline oxidative
      conditions of the midgut of insect larvae and to reveal the alkaline and
      enzymatic oxidative activities for individual phenolic compounds present in the
      larval host plants. First, we monitored the in vitro isomerization of 5-O
      caffeoylquinic acid (5-CQA) into 3-CQA, 4-CQA and 5-CQA at pH 9.0-11.0. Then we
      calculated the isomer ratios of 3-CQA, 4-CQA and 5-CQA from the frass of eight
      species of insect herbivores fed on foliage containing 5-CQA. The isomer ratios
      suggested that the midgut pH of these larvae ranged from 9.4 to around 10.1.
      Second, we developed an in situ enzymatic oxidation method that enabled oxidation
      of phenolics in a frozen plant sample at 30  degrees C by species- and tissue
      specific enzymes. Then we measured the alkaline and enzymatic oxidative
      activities of the individual phenolics in 20 plant species by quantifying the
      proportion of the compound concentration lost due to the auto-oxidation of a
      plant extract at pH 10 and due to the enzymatic oxidation of the frozen plant
      sample at 30  degrees C. Our results showed that both of the oxidative activity
      types depended primarily on the type of phenolic compound, but the enzymatic
      oxidative activity depended also on the plant species and tissue type. This
      combination of methods offers an approach to characterize a wide array of
      phenolics that are susceptible to oxidation by the plant enzymes and/or by the
      alkaline conditions estimated to prevail in the insect midgut. We propose that
      these kinds of compound-specific results could guide future studies on specific
      plant-herbivore interactions to focus on the phenolics that are likely to be
      active rather than inactive plant phenolics.

PMID- 29637495
TI  - High-throughput genetic screens using CRISPR-Cas9 system.
AB  - The CRISPR-Cas9 system is a powerful tool for genome engineering, and its
      programmability and simplicity have enabled various types of gene manipulation
      such as gene disruption and transcriptional and epigenetic perturbation.
      Particularly, CRISPR-based pooled libraries facilitate high-throughput screening
      for functional regulatory elements in the human genome. In this review, we
      describe recent advances in CRISPR-Cas9 technology and its use in high-throughput
      genetic screening. We also discuss its potential for drug target discovery and
      current challenges of this technique in biomedical research.

PMID- 29637493
TI  - The Underrated Risks of Tamoxifen Drug Interactions.
AB  - Tamoxifen is a prodrug, and most of the therapeutic effect in treating breast
      cancer stems from its metabolite, endoxifen. Since cytochrome P450 (CYP) 2D6 is
      the most important enzyme in the production of endoxifen, drugs that inhibit
      CYP2D6 would be expected to reduce tamoxifen efficacy. In addition to drug-drug
      interactions (DDI) involving CYP2D6, there is growing evidence that enzyme
      inducers can substantially alter the disposition of endoxifen, reducing tamoxifen
      efficacy. Although the clinical evidence on the impact of CYP2D6 inhibitors on
      tamoxifen efficacy is mixed, there were serious flaws in many of the studies.
      Thus, there is a reasonable chance that CYP2D6 inhibitors do in fact inhibit
      tamoxifen efficacy. Tamoxifen has extraordinarily complex pharmacokinetics, with
      more than a dozen drug-metabolizing enzymes and transporters involved in its
      disposition. Enzyme inducers may increase the activity of several of these
      pathways, including phase II enzymes, ABC transporters, and various CYP enzymes
      other than CYP2D6. Based on current clinical evidence, one could argue that
      enzyme inducers are potentially more dangerous than CYP2D6 inhibitors in patients
      taking tamoxifen. Moreover, early evidence suggests that the combination of
      CYP2D6 inhibitors plus enzyme inducers may produce catastrophic inhibition of
      tamoxifen efficacy. One could argue that, given the available evidence, an
      agnostic "wait and see" position on tamoxifen DDI is ethically untenable, and
      that many women with breast cancer are currently being subjected to an
      unnecessary risk of cancer recurrence. Specific recommendations to reduce the
      risk of adverse tamoxifen DDI are offered for consideration.

PMID- 29637494
TI  - Comparison of the size distributions and immunogenicity of human papillomavirus
      type 16 L1 virus-like particles produced in insect and yeast cells.
AB  - Insect and yeast cells are considered the expression systems of choice for
      producing virus-like particles (VLPs), and numerous types of VLPs have been
      produced in these systems. However, previous studies were restricted to
      identifying the characteristics of individual VLP preparations. No direct
      comparison of the structures and immunogenic properties of insect and yeast
      derived VLPs has so far been made. In the present study, the size distribution
      and immunogenic properties of human papillomavirus type 16 (HPV16) L1 VLPs
      produced in Spodoptera frugipedra-9 insect cells and Saccharomyces cerevisiae
      were compared. The insect cell-derived VLPs were larger than the yeast ones (P <
      0.0001), with median sizes of 34 and 26 nm, respectively. In addition, the insect
      derived VLPs appeared to be more diverse in size than the yeast-derived VLPs.
      Immunization of mice with 30 ng per dose of VLPs elicited 2.7- and 2.4-fold
      higher anti-HPV16 L1 IgG and anti-HPV16 neutralizing antibody titers than
      immunization with the same amounts of the yeast-derived VLPs after the 4th
      immunizations, respectively. Our results suggest that the choice of expression
      system critically affects the particle size and immunogenic property of HPV16 L1
      VLPs.

PMID- 29637496
TI  - Preparation and Optimization of Rivaroxaban by Self-Nanoemulsifying Drug Delivery
      System (SNEDDS) for Enhanced Oral Bioavailability and No Food Effect.
AB  - In this paper, a novel self-nanoemulsifying drug delivery system (SNEDDS) was
      used to improve the oral bioavailability in fasted state and diminish the food
      effect for rivaroxaban. Oil, surfactant, and co-surfactant were selected by
      saturated solubility study. IPM, Tween80, and 1,2-propanediol were finally
      selected as oil, surfactant, and co-surfactant, respectively. The pseudo-ternary
      phase diagram was utilized to optimize the preliminary composition of SNEDDS
      formulation. The optimized rivaroxaban-SNEDDS formulation was selected by central
      composite design (CCD) of response surface methodology. Optimized SNEDDS
      formulation was evaluated for drug content, self-emulsifying time, droplet size,
      zeta potential, polydispersity index, Fourier transform-infrared (FTIR)
      spectroscopy, and transmission electron microscope (TEM). The drug dissolution
      profile compared to the commercial formulation Xarelto(r) (20 mg rivaroxaban) was
      determined in four different media (pH 1.2HCl, pH 4.5NaAc-HAc, pH 6.8PBS, and
      water). The result indicated that the SNEDDS formulation had successfully
      increased the drug solubility in four different media. A HPLC-MS method that
      indicated a high sensitivity, strong attribute, and high accuracy characteristic
      was built to measure the drug concentration in plasma. The fast/fed in vivo
      pharmacokinetics studies of SNEDDS formulation and Xarelto(r) were carried out in
      adult beagle dog, rivaroxaban with no food effect was achieved in SNEDDS
      formulation compared with Xarelto(r) in fed state. The result suggested that
      SNEDDS formulation in this study is useful to increase the oral bioavailability
      and diminish the food effect in fasted state.

PMID- 29637497
TI  - Microemulsion Formulations for the Transdermal Delivery of Lapachol.
AB  - This project was carried out to investigate the feasibility of using
      microemulsions for transdermal delivery of lapachol. From the screening of
      surfactants and oils, a range of microemulsions were developed using oleic acid,
      a mixture of Cremophor EL and Tween 20 and water. The solubility of lapachol was
      determined in these ingredients and in the formulated microemulsions. The
      microemulsions were characterised using cross-polarising light microscopy, their
      electrical conductivity, pH, zeta potential and rheology were analysed, and they
      were also investigated using small-angle X-ray scattering and differential
      scanning calorimetry. Ex vivo studies were performed using porcine ear skin and
      Franz diffusion cells to investigate the permeation and retention of lapachol.
      Systems containing different concentrations of Cremophor EL (8.4-41.6%), Tween 20
      (5.4-41.6%) and oleic acid (12-31.9%) are able to form microemulsions. Lapachol
      was delivered more effectively through the skin from all of the microemulsions
      tested than by the control (oleic acid). These studies indicated that
      microemulsions incorporating lapachol were formed successfully and that these
      enhanced drug delivery and retention in the skin. Microemulsion systems may,
      therefore, provide promising vehicles for percutaneous delivery of lapachol.

PMID- 29637498
TI  - Impact of Physicochemical Properties of Cellulosic Polymers on Supersaturation
      Maintenance in Aqueous Drug Solutions.
AB  - The precipitation inhibitory effect of cellulosic polymers in relation to their
      physicochemical properties was studied. Using a poorly water-soluble model drug,
      griseofulvin, the precipitation inhibitory effect of a series of hydroxypropyl
      methylcellulose (HPMC) and methylcellulose polymers was studied using solvent
      shift method. The extent of supersaturation maintenance of each polymer was then
      quantified by the parameter, supersaturation factor (SF). Partial least square
      (PLS) regression analysis was employed to understand the relative contribution
      from viscosity, hydroxypropyl content (HC), methoxyl content,
      methoxyl/hydroxypropyl ratio, and drug-polymer interaction parameter (chi) on SF.
      All grades of cellulosic polymers effectively prolonged supersaturation of
      griseofulvin. PLS regression analysis revealed that HC and chi appeared to have
      the strongest influence on SF response. A regression model of SF = 1.65-0.16 chi
      + 0.05 HC with a high correlation coefficient, r of 0.921, was obtained. Since
      the value of chi is inversely related to the strength of drug-polymer
      interaction, the result shows that SF increases with increasing drug-polymer
      interaction and increasing HC. As such, it can be implied that strong drug
      polymer interaction and presence of hydroxypropyl groups in cellulosic polymers
      for hydrogen bonding are two key parameters for effective supersaturation
      maintenance. This knowledge on the relative contribution of polymer
      physicochemical properties on precipitation inhibition will allow the selection
      of suitable cellulosic polymers for systematic development of supersaturating
      drug delivery systems.

PMID- 29637499
TI  - The Transitional Cardiac Pumping Mechanics in the Embryonic Heart.
AB  - Several studies have linked abnormal blood flow dynamics to the formation of
      congenital heart defects during the early stages of development. The objective of
      this study is to document the transition of pumping mechanics from the early tube
      stage to the late looping stage of the embryonic heart. The optically transparent
      zebrafish embryonic heart was utilized as the in vivo model and was studied using
      standard bright field microscopy at three relevant stages within the transitional
      period: (1) tube stage at 30 hours post-fertilization (hpf); (2) early cardiac
      looping stage at 36 hpf; and (3) late cardiac looping stage at 48 hpf. High-speed
      videos were collected at 1000 fps at a spatial resolution of 1.1 MUm/pixel at
      each of these stages and were post-processed to yield blood velocity patterns as
      well as wall kinematics. Results show that several relevant trends exist.
      Morphological trends from tube through late looping include: (a) ballooning of
      the chambers, (b) increasing constriction at the atrioventricular junction (AVJ),
      and (c) repositioning of the ventricle toward the side of the atrium. Blood flow
      trends include: (a) higher blood velocities, (b) increased AVJ regurgitation, and
      (c) larger percentages of blood from the upper atrium expelled backward toward
      the atrial inlet. Pumping mechanics trends include: (a) increasing contraction
      wave delay at the AVJ, (b) the AVJ begins acting as a rudimentary valve, (c)
      decreasing chamber constriction during maximum contraction, and (d) a transition
      in ventricular kinematics from a pronounced propagating wave to an independent,
      full-chamber contraction. The above results provide new insight into the
      transitional pumping mechanics from peristalsis-like pumping to a displacement
      pumping mechanism.

PMID- 29637500
TI  - Cardiovascular Development and Angiogenesis in the Early Vertebrate Embryo.
AB  - Embryonic cardiovascular physiology (as opposed to that of the more developed
      fetus) is being more closely examined by developmental physiologists to explore
      the onset of cardiovascular function and its regulation, as opposed to the later
      maturation of these processes as is typically examined in fetal mammal models. As
      our understanding of embryonic physiology grows, the dogma that the early
      embryonic heart serves the same convective bulk transport role that it does in
      the fetal and adult heart is being carefully evaluated. Experimental approaches
      have involved genetic, surgical and environmental manipulation, and have revealed
      that blood flow generated by the early embryonic heart is not required for bulk
      transport of respiratory gases, nutrients, and wastes. Rather, the very small
      size of the typical vertebrate embryo enables this critical transport function to
      be achieved by simple diffusion alone. Surprisingly, however, the heart begins to
      beat (and so expend valuable energy) well before convective blood circulation is
      actually required. This review postulates that angiogenesis may be a driving
      factor for the "early" beat of the heart. Recent experiments examining the effect
      of increased blood pressure and flow pulsatility on proximal blood vessel
      development offer initial support for the "synangiotropy" hypothesis, namely that
      the onset of heart beat occurs synchronously with the need for peripheral
      angiogenesis. Yet, the complexity of the patterns of angiogenesis (regional
      variations of opposite sign) suggests that we have much more to be learned about
      the relationship between angiogenesis and the circulation in vertebrate embryos.

PMID- 29637501
TI  - Erratum to: The Transitional Cardiac Pumping Mechanics in the Embryonic Heart.

PMID- 29637502
TI  - How Do Cord Compressions Affect the Umbilical Venous Flow Resistance? An In Vitro
      Investigation of the Biomechanical Mechanisms.
AB  - Umbilical vessels, that provide blood oxygenation and fetal nourishment in utero,
      are encased and protected against external forces by the umbilical cord. The
      biomechanics of this peculiar structure has not been deeply investigated so far.
      The purpose of this study is to investigate the hydraulic behaviour of human
      umbilical veins (UV) and its changes in presence of an external cord compression.
      Five umbilical cords were subjected to in vitro tests. UV was accurately
      cannulated and connected to a perfusion circuit, while the cord was subjected to
      an external compression. Pressure drops across UV were measured for various
      venous flow rates and various degrees of cord constriction. Compressive forces
      were measured, too. The UV hydraulic resistances measured in unloaded cords
      (0.029 +/- 0.016 mmHg min cm-1 L-1) correspond to placenta-abdomen pressure drops
      well consistent with in utero measurements. As expected, at fixed flow rate, flow
      resistance augments when cord is compressed. Interestingly, resistance does not
      substantially change until a 30-50% cord thickness reduction, whereas slightly
      larger constriction cause a steep increase. Compressive forces becomes critical
      for values above 0.5-2 N, depending on the length of cord compression and on
      considered specimen. Moreover, at high cord constriction, hydraulic behaviour of
      UV is very peculiar. Namely, the slope of the pressure-flow relationship
      decreases at increasing flow rates and, in few cases, a surprising reduction of
      pressure drop was even observed. The biomechanical behaviour of the umbilical
      cord during compression is very complex, with high non-linearity of venous
      hydraulic behaviour.

PMID- 29637503
TI  - Human Ductus Venosus Velocity Profiles in the First Trimester.
AB  - The fluid dynamics in the human fetal ductus venosus in the early stage of
      pregnancy is not well explored. Consequently, there is an uncertainty in the
      interpretation of the temporal and spatial velocity variation in the ductus
      venosus. A robust estimation procedure for non-invasive measurement of the blood
      flow, based on conventional Doppler ultrasound measurements, is therefore
      missing. The aim of the present study was to describe the spatial and temporal
      velocity distribution at the ductus venosus bifurcation for boundary condition
      typical for fetuses at 11-13 weeks of gestation by means of a mathematical model.
      In particular we wanted to investigate velocity profiles at the ductus venosus
      inlet region in early pregnancy under normal conditions, to assess whether robust
      estimates of velocity profile shape coefficients may be given in order to provide
      noninvasive volumetric flow rate assessment in the ductus venosus. Such
      information will be useful in a clinical assessment of the fetus. Our model
      predicted a close to parabolic velocity profile in the inlet section of the
      ductus venosus during the cardiac cycle, with a shape factor of 0.53. Our
      simulations also showed that during atrial contraction (the A-wave), transient
      simultaneous positive and negative velocities may be observed in the same cross
      section, in Womersley-like velocity profiles. Thus, as previous clinical
      investigators have reported these velocities as either positive or negative, our
      findings challenge clinical interpretation.

PMID- 29637504
TI  - Functional Imaging in Fetal Echocardiography: A Review of Conventional and Novel
      Approaches.
AB  - Advances in fetal cardiac imaging have resulted in changes in the practice of
      fetal cardiology, and in improved neonatal outcomes for these patients. As the
      anatomic diagnostic accuracy of fetal cardiology has improved, cardiologists have
      sought new challenges in fetal imaging, and with new emphasis on improved front
      line detection, treatment/intervention during fetal life, and assessment of fetal
      ventricular function and cardiovascular performance. The evolution of noninvasive
      assessment of fetal cardiac function is related to technologic advances in
      ultrasound imaging. This article reviews conventional methods of the assessment
      of cardiac function, as well as some promising directions for future evaluation
      with emphasis on future applications of 3D echocardiography and 3D speckle
      tracking echocardiography.

PMID- 29637505
TI  - Guest Editorial: Special Issue on Fetal Hemodynamics : Developmental Fetal
      Cardiovascular Biomechanics in the 21st Century: Another Tipping Point.

PMID- 29637506
TI  - Lower blastocyst quality after conventional vs. Piezo ICSI in the horse reflects
      delayed sperm component remodeling and oocyte activation.
AB  - PURPOSE: The aim of this study was to evaluate the differential effects of
      conventional and Piezo-driven ICSI on blastocyst development, and on sperm
      component remodeling and oocyte activation, in an equine model. METHODS: In vitro
      matured equine oocytes underwent conventional (Conv) or Piezo ICSI, the latter
      utilizing fluorocarbon ballast. Blastocyst development was compared between
      treatments to validate the model. Then, oocytes were fixed at 0, 6, or 18 h after
      injection, and stained for the sperm tail, acrosome, oocyte cortical granules,
      and chromatin. These parameters were compared between injection techniques and
      between sham-injected and sperm-injected oocytes among time periods. RESULTS:
      Blastocyst rates were 39 and 40%. The nucleus number was lower, and the nuclear
      fragmentation rate was higher, in blastocysts produced by Conv. Cortical granule
      loss started at 0H after both sperm and sham injection. The acrosome was present
      at 0H in both ICSI treatments, and persisted to 18H in significantly more Conv
      than Piezo oocytes (72 vs. 21%). Sperm head area was unchanged at 6H in Conv but
      significantly increased at this time in Piezo; correspondingly, at 6H
      significantly more Conv than Piezo oocytes remained at MII (80 vs. 9.5%). Sham
      injection did not induce significant meiotic resumption. CONCLUSIONS: These data
      show that Piezo ICSI is associated with more rapid sperm component remodeling and
      oocyte meiotic resumption after sperm injection than is conventional ICSI, and
      with higher embryo quality at the blastocyst stage. This suggests that there is
      value in exploring the Piezo technique, utilized with a non-toxic fluorocarbon
      ballast, for use in clinical human ICSI.

PMID- 29637507
TI  - The Cerebello-Hypothalamic and Hypothalamo-Cerebellar Pathways via Superior and
      Middle Cerebellar Peduncle in the Rat.
AB  - The connections between the cerebellum and the hypothalamus have been well
      documented. However, the specific cerebellar peduncle through which the
      hypothalamo-cerebellar and cerebello-hypothalamic connections pass has not been
      demonstrated. The present study aims to define the specific cerebellar peduncle
      through which connects the cerebellum to specific hypothalamic nuclei. Seventeen
      male albino rats received 20-50-nl pressure injections of either Fluoro-Gold (FG)
      or biotinylated dextran amine (BDA) tracer into the superior (SCP), middle (MCP),
      and inferior (ICP) cerebellar peduncle. Following 7-10 days of survival period,
      the animals were processed according to the appropriate protocol for the two
      tracers used. Labeled cells and axons were documented using light or fluorescence
      microscopy. The present study showed connections between the hypothalamus and the
      cerebellum via both the SCP and the MCP but not the ICP. The hypothalamo
      cerebellar connections via the SCP were from the lateral, dorsomedial,
      paraventricular, and posterior hypothalamic nuclei, and cerebello-hypothalamic
      connections were to the preoptic and lateral hypothalamic nuclei. The hypothalamo
      cerebellar connections via the MCP were from the lateral, dorsomedial,
      ventromedial, and mammillary hypothalamic nuclei; and cerebello-hypothalamic
      connections were to the posterior, arcuate, and ventromedial hypothalamic nuclei.
      The hypothlamo-cerebellar connections were denser compared to the cerebello
      hypothlamic connections via both the SCP and the MCP. The connection between the
      cerebellum and the hypothalamus was more prominent via the SCP than MCP. Both the
      hypothlamo-cerebellar and cerebello-hypothalamic connections were bilateral, with
      ipsilateral preponderance. Reciprocal connections were with the lateral
      hypothalamic nucleus via the SCP and the ventromedial nucleus via the MCP were
      observed. Cerebellum takes part in the higher order brain functions via its
      extensive connections. The knowledge of hypothalamo-cerebellar and cerebello
      hypothalamic connections conveyed within the SCP and MCP can be important for the
      lesions involving the MCP and SCP. These connections can also change the
      conceptual architecture of the cerebellar circuitry and deepen current
      understanding.

PMID- 29637508
TI  - Intraoperative linguistic performance during awake brain surgery predicts
      postoperative linguistic deficits.
AB  - INTRODUCTION: Awake craniotomy pursues a balance between extensive tumor
      resection and preservation of postoperative language function. A dilemma exists
      in patients whose tumor resection is restricted due to signs of language
      impairment observed during awake craniotomy. In order to determine the degree to
      which recovery of language function caused by tumor resection can be achieved by
      spontaneous neuroplasticity, the change in postoperative language function was
      compared to quantified intraoperative linguistic performance. METHODS: The
      modified, short-form Boston Diagnostic Aphasia Examination (sfBDAE) was used to
      assess pre- and postoperative language functions; visual object naming (DO 80)
      and semantic-association (Pyramid and Palm Tree Test, PPTT) tests assessed
      intraoperative linguistic performance. DO 80 and PPTT were performed
      alternatively during subcortical functional monitoring while performing tumor
      resection and sfBDAE was assessed 1-week postoperatively. RESULTS: Most patients
      with observed language impairment during awake surgery showed improved language
      function postoperatively. Both intraoperative DO 80 and PPTT showed significant
      correlation to postoperative sfBDAE domain scores (p < 0.05), with a higher
      correlation observed with PPTT. A linear regression model showed that only PPTT
      predicted the postoperative sfBDAE domain scores with the adjusted R2 ranging
      from 0.51 to 0.89 (all p < 0.01). Receiver operating characteristic analysis
      showed a cutoff value of PPTT that yielded a sensitivity of 80% and specificity
      of 100%. CONCLUSION: PPTT may be a feasible tool for intraoperative linguistic
      evaluation that can predict postoperative language outcomes. Further studies are
      needed to determine the extent of tumor resection that optimizes the
      postoperative language following neuroplasticity.

PMID- 29637510
TI  - Information needs and requirements in patients with brain tumours.

PMID- 29637509
TI  - Safety, efficacy and survival of patients with primary malignant brain tumours
      (PMBT) in phase I (Ph1) trials: the 12-year Royal Marsden experience.
AB  - BACKGROUND: Primary malignant brain tumours (PMBT) constitute less than 2% of all
      malignancies and carry a dismal prognosis. Treatment options at relapse are
      limited. First-in-human solid tumour studies have historically excluded patients
      with PMBT due to the poor prognosis, concomitant drug interactions and concerns
      regarding toxicities. METHODS: Retrospective data were collected on clinical and
      tumour characteristics of patients referred for consideration of Ph1 trials in
      the Royal Marsden Hospital between June 2004 and August 2016. Survival analyses
      were performed using the Kaplan-Meier method, Cox proportional hazards model. Chi
      squared test was used to measure bivariate associations between categorical
      variables. RESULTS: 100pts with advanced PMBT were referred. At initial
      consultation, patients had a median ECOG PS 1, median age 48 years (range 18-70);
      69% were men, 76% had glioblastoma; 68% were on AEDs, 63% required steroid
      therapy; median number of prior treatments was two. Median OS for patients
      treated on a Ph1 trials was 9.3 months (95% CI 5.9-12.9) versus 5.3 months (95%
      CI 4.1-6.1) for patients that did not proceed with a Ph1 trial, p = 0.0094.
      Steroid use, poor PS, neutrophil-to-lymphocyte ratio and treatment on a Ph1 trial
      were shown to independently influence OS. CONCLUSIONS: We report a survival
      benefit for patients with PMBT treated on Ph1 trials. Toxicity and efficacy
      outcomes were comparable to the general Ph1 population. In the absence of an
      internationally recognized standard second line treatment for patients with
      recurrent PMBT, more Ph1 trials should allow enrolment of patients with
      refractory PMBT and Ph1 trial participation should be considered at an earlier
      stage.

PMID- 29637512
TI  - Psychiatry's Role in Responding to Climate Change.

PMID- 29637511
TI  - Ledipasvir/sofosbuvir for treatment-naive and treatment-experienced Chinese
      patients with genotype 1 HCV: an open-label, phase 3b study.
AB  - BACKGROUND: Chronic hepatitis C virus (HCV) infection is a significant medical
      burden in China, affecting more than 10 million persons. In clinical trials and
      real-world settings, treatment with ledipasvir/sofosbuvir in patients with
      genotype 1 HCV infection resulted in high sustained virologic response rates.
      Ledipasvir/sofosbuvir may provide a highly effective, short-duration, single
      tablet regimen for Chinese patients with HCV infection. METHODS: Chinese patients
      with genotype 1 HCV infection who were HCV treatment naive or treatment
      experienced, without cirrhosis or with compensated cirrhosis, were treated with
      open-label ledipasvir/sofosbuvir for 12 weeks. The primary efficacy endpoint was
      sustained virologic response 12 weeks after completing treatment (SVR12). For
      treatment-naive patients, SVR12 was compared to a historical rate of 57%. The
      primary safety endpoint was adverse events leading to permanent discontinuation
      of study drug; serious adverse events were also evaluated. The presence of
      resistance-associated substitutions (RASs) was evaluated by viral sequencing.
      RESULTS: All 206 enrolled patients achieved SVR12 (100%; 95% CI 98-100%),
      including 106 treatment-naive patients (100%; 95% CI 97-100%), which was superior
      to a historical SVR rate of 57% (p < 0.001). All patients with baseline NS5A and
      NS5B RASs (14 and 1% of patients, respectively) achieved SVR12. The most common
      adverse events were viral upper respiratory tract infection (17%), upper
      respiratory tract infection (14%), and cough (6%). There were no discontinuations
      due to adverse events; and no treatment-related serious adverse events were
      reported. CONCLUSION: Ledipasvir/sofosbuvir is a well tolerated and highly
      effective treatment for Chinese patients with genotype 1 HCV, regardless of prior
      treatment experience, cirrhosis status, or the presence of pretreatment RASs.

PMID- 29637513
TI  - Comment on "Examining Burnout, Depression, and Attitudes Regarding Drug Use Among
      Lebanese Medical Students During the 4 Years of Medical School".

PMID- 29637514
TI  - Smart Steps for Psychiatric Education: Approaching Smartphone Apps for Learning
      and Care.

PMID- 29637515
TI  - Continuous Quality Improvement for Psychiatry Residency Didactic Curricula.

PMID- 29637516
TI  - Erratum to: Spinocerebellar Ataxia Type 6: Molecular Mechanisms and Calcium
      Channel Genetics.

PMID- 29637517
TI  - Prognostic Factors for Operated Gallbladder Cancer.
AB  - PURPOSE: The prognosis of gallbladder cancer is poor. Lymph node metastasis and
      the stage are known to be the strongest prognostic factors for survival. The aim
      of this study was to determine the importance of complementary surgery and other
      prognostic factors for survival of operated gallbladder cancer. MATERIAL AND
      METHOD: We retrospectively analyzed 62 localized gallbladder cancers. The
      prognostic factors for survival were evaluated by univariate and multivariate
      analysis. RESULTS: The 3-year overall survival (OS) and disease-free survival
      (DFS) rates were 52.8 and 43.5%, respectively. Totally, 37 patients (59.6%) were
      diagnosed incidentally during simple cholecystectomy which was performed for
      benign causes but only 56.4% of them underwent complementary surgery. 51.6% of
      the recurrence was detected during 18.4 months of follow-up time. R0 resection, T
      stage, and pathological stage were found to be related with both OS and DFS by
      univariate analysis. Grade, lymph node metastasis, and adjuvant chemotherapy were
      also related with DFS. Presence of recurrence, recurrence side, performance score
      (PS), and perineural invasion (PNI) were related with OS. Peritoneal metastasis,
      advanced stage disease, and lymph node metastasis were more common among patients
      who did not undergo complementary surgery. Adjuvant chemotherapy was given more
      frequently to patients who undergone complementary surgery group. The
      multivariate analysis indicated that grade, lymph node metastasis, stage,
      recurrence site, PS, and adjuvant chemotherapy stage were independent prognostic
      factors for DFS on the other and only stage was a prognostic factor for OS.
      CONCLUSION: Our results showed that incidental diagnosis or complementary surgery
      was not related with DFS or OS but stage was only an independent prognostic
      factor for both OS and DFS in resected gallbladder cancer.

PMID- 29637518
TI  - Cerebrovascular Events After Continuous-Flow Left Ventricular Assist Devices.
AB  - BACKGROUND: Cerebrovascular events (CVE) are among the most common and serious
      complications after implantation of continuous-flow left ventricular assist
      devices (CF-LVAD). We studied the incidence, subtypes, anatomical distribution,
      and pre- and post-implantation risk factors of CVEs as well as the effect of CVEs
      on outcomes after CF-LVAD implantation at our institution. METHODS: Retrospective
      analysis of clinical and neuroimaging data of 372 patients with CF-LVAD between
      May 2005 and December 2013 using standard statistical methods. RESULTS: CVEs
      occurred in 71 patients (19%), consisting of 35 ischemic (49%), 26 hemorrhagic
      (37%), and 10 ischemic+hemorrhagic (14%) events. History of coronary artery
      disease and female gender was associated with higher odds of ischemic CVE (OR
      2.84 and 2.5, respectively), and diabetes mellitus was associated with higher
      odds of hemorrhagic CVE (OR 3.12). While we found a higher rate of ischemic CVEs
      in patients not taking any antithrombotic medications, no difference was found
      between patients with ischemic and hemorrhagic CVEs. Occurrence of CVEs was
      associated with increased mortality (HR 1.62). Heart transplantation was
      associated with improved survival (HR 0.02). In patients without heart
      transplantation, occurrence of CVE was associated with decreased survival.
      CONCLUSIONS: LVADs are associated with high rates of CVE, increased mortality,
      and lower rates of heart transplantation. Further investigations to identify the
      optimal primary and secondary stroke prevention measures in post-LVAD patients
      are warranted.

PMID- 29637520
TI  - Obligatory exercise and coping in treatment-seeking women with poor body image.
AB  - PURPOSE: Obligatory exercise is characterized by continued exercise despite
      negative consequences, and intense negative affect when unable to exercise.
      Research suggests psychosocial differences between individuals that exercise in
      an obligatory manner and those that do not. It also has been speculated that
      obligatory exercise may serve coping and affect regulation functions, yet these
      factors have not been routinely examined in community women with poor body image.
      The purpose of the current study was to investigate psychosocial differences
      between obligatory and non-obligatory exercisers, and to examine the use of
      obligatory exercise as an avoidant coping strategy in a sample of women with poor
      body image. METHODS: Women (n = 70) seeking treatment for body dissatisfaction
      were divided into obligatory and non-obligatory exercise groups based on their
      scores on the Obligatory Exercise Questionnaire. Participants then completed an
      assessment battery about eating pathology, body image, reasons for exercise,
      coping strategies, and negative affect. RESULTS: Independent t test analyses
      indicated that obligatory exercisers had significantly greater eating disorder
      symptomatology, avoidant coping, and appearance- and mood-related reasons for
      exercise than non-obligatory exercisers. Multiple regression analyses revealed
      that eating disorder symptomatology and avoidant coping were significant
      predictors of obligatory exercise. CONCLUSIONS: There are distinct psychosocial
      differences between women with poor body image who exercise in an obligatory
      fashion and those who do not. The current study suggests that obligatory exercise
      may serve as an avoidant coping strategy for women with poor body image.
      Enhancing healthy coping strategies may be an important addition to body image
      improvement programs. LEVEL OF EVIDENCE: V, cross-sectional descriptive study.

PMID- 29637519
TI  - Clinical Management of Osteoporotic Fractures.
AB  - PURPOSE OF REVIEW: This review examines recent literature regarding the clinical
      management of fragility fractures, provides insight into new practice patterns,
      and discusses controversies in current management. RECENT FINDINGS: There are
      declining rates of osteoporosis management following initial fragility fracture.
      Management of osteoporotic fractures via a multidisciplinary team reduces
      secondary fracture incidence and improves overall osteoporotic care. Anabolic
      agents (abaloparatide and teriparatide) are effective adjuvants to fracture
      repair, and have shown positive results in cases of re-fracture in spite of
      medical management (i.e., bisphosphonates). For AO 31-A1 and A2 intertrochanteric
      hip fractures (non-reverse obliquity), no clinical advantage of intramedullary
      fixation over the sliding hip screw (SHS) has been proven; SHS is more cost
      effective. As fragility fracture incidence continues to rise, orthopedic surgeons
      must play a more central role in the care of osteoporotic patients. Initiation of
      pharmacologic intervention is key to preventing subsequent fragility fractures,
      and may play a supportive role in initial fracture healing. While the media
      bombards patients with complications of medical therapy (atypical femur
      fractures, osteonecrosis of jaw, myocardial infarction), providers need to
      understand and communicate the low incidence of these complications compared with
      consequences of not initiating medical therapy.

PMID- 29637522
TI  - Molecular, Morphological, and Biological Differentiation between Anagrus virlai
      sp. n., an Egg Parasitoid of the Corn Leafhopper Dalbulus maidis (Hemiptera:
      Cicadellidae) in the New World, and Anagrus incarnatus from the Palaearctic
      Region (Hymenoptera: Mymaridae).
AB  - The common New World egg parasitoid of the corn leafhopper Dalbulus maidis
      (DeLong) (Hemiptera: Cicadellidae), an economically important pest of maize from
      Argentina to southern USA, has long been misidentified as the Palaearctic species
      Anagrus incarnatus Haliday or its synonym A. breviphragma Soyka (Hymenoptera:
      Mymaridae). Using a combination of genetic and morphometric methods, and
      available biological information, specimens reared from eggs of D. maidis in
      Argentina and Mexico, described and illustrated here as Anagrus (Anagrus) virlai
      Triapitsyn sp. n., are shown to be different from those of A. incarnatus from the
      Palaearctic region. Mitochondrial and nuclear ribosomal DNA sequence data provide
      clear evidence for the separation of the two species. Anagrus virlai is also
      known from Brazil, Colombia, Guadeloupe (France), and Guyana.

PMID- 29637521
TI  - The obesity paradox and osteoporosis.
AB  - Overweight and obesity according to the definition of the WHO are considered as
      an abnormal or excessive fat accumulation that may impair health. Studies
      comparing fracture incidence in obese and non-obese individuals have demonstrated
      that obesity, defined on the basis of body mass index (BMI), is associated with
      increased risk of fracture at some sites but seems to be protective at others.
      The results of the studies are influenced by the distribution of BMI in the
      population studied; for example, in cohorts with a low prevalence of obesity, a
      predilection for certain fracture sites in obese individuals becomes difficult to
      detect, whereas, in populations with a high prevalence of obesity, previously
      unreported associations may emerge. Furthermore, obesity can bring with itself
      many complications (Type 2 diabetes mellitus, vitamin D deficiency, and motor
      disability) which, in the long run, can have a definite influence in terms of
      overall risk and quality of life, as well. This is a narrative review focusing on
      the relationship between bone metabolism and overweight/obesity and dealing with
      the fundamental dilemma of a disease (obesity) apparently associated with
      improved values of bone mineral density, part of a complicated relationship which
      revolves around obesity called "the obesity paradox".

PMID- 29637523
TI  - Coronary circulation: Pressure/flow parameters for assessment of ischemic heart
      disease.
AB  - Both invasive and non-invasive parameters have been reported for assessment of
      the physiological status of the coronary circulation. Fractional flow reserve and
      coronary (or myocardial) flow reserve may be obtained by invasive or non-invasive
      means. These metrics of coronary stenosis severity have achieved wide clinical
      acceptance for guiding revascularization decisions and risk stratification. Other
      indices are obtained invasively (e.g., instantaneous wave-free ratio, iFR;
      hyperemic stenosis resistance) or non-invasively (e.g., PET absolute myocardial
      blood flow (mL/min/g)) and have been used for the same purposes. Both iFR, and
      whole-cycle distal coronary to aortic mean pressure (Pd/Pa) are measured under
      basal condition and used for assessment of hemodynamic stenosis severity as is
      index of basal stenosis resistance (BSR). These metrics typically are
      dichotomized at an empirically derived cut point into "normal" and "abnormal"
      categories for purposes of clinical decision making and data analysis. Once
      dichotomized the indices do not always point in the same direction and so
      confusion may arise. This review, therefore, will present basic principles
      relevant to understanding commonly employed metrics of the physiological status
      of the coronary circulation, potential strengths and weaknesses, and hopefully an
      improved appreciation of the clinical information provided by each.

PMID- 29637524
TI  - Correction to: Clinical Quantification of Myocardial Blood Flow Using PET: Joint
      Position Paper of the SNMMI Cardiovascular Council and the ASNC.
AB  - The above position statement originally published containing errors in the author
      metadata; specifically, the Expert Content Reviewers-Andrew Einstein, Raymond
      Russell and James R. Corbett-were tagged as full authors of the paper. The
      article metadata has now been corrected to remove Drs. Einstein, Russell and
      Corbett from the author line, and the PubMed record has been updated accordingly.

PMID- 29637525
TI  - The continual innovation of commercial PET/CT solutions in nuclear cardiology:
      Siemens Healthineers.
AB  - Cardiac PET/CT is an evolving, non-invasive imaging modality that impacts patient
      management in many clinical scenarios. Beyond offering the capability to assess
      myocardial perfusion, inflammatory cardiac pathologies, and myocardial viability,
      cardiac PET/CT also allows for the non-invasive quantitative assessment of
      myocardial blood flow (MBF) and myocardial flow reserve (MFR). Recognizing the
      need for an enhanced comprehension of coronary physiology, Siemens Healthineers
      implemented a sophisticated solution for the calculation of MBF and MFR in 2009.
      As a result, each aspect of their innovative scanner and image-processing
      technology seamlessly integrates into an efficient, easy-to-use workflow for
      everyday clinical use that maximizes the number of patients who potentially
      benefit from this imaging modality.

PMID- 29637526
TI  - Drug Discrimination: Historical Origins, Important Concepts, and Principles.
AB  - Research on the stimulus properties of drugs began with studies on state
      dependent learning during the first half of the twentieth century. From that
      research, an entirely new approach evolved called drug discrimination. Animals
      (including humans) could discriminate the presence or absence of a drug; once
      learned, the drug could serve as a discriminative stimulus, signaling the
      availability or nonavailability of reinforcement. Early drug discrimination
      research involved the use of a T-maze task, which evolved in the 1970s into a two
      lever operant drug discrimination task that is still used today. A number of
      important concepts and principles of drug discrimination are discussed. (1) The
      discriminative stimulus properties of drugs are believed in large part to reflect
      the subjective effects of drugs. While it has been impossible to directly measure
      subjective effects in nonhuman animals, drug discrimination studies in human
      subjects have generally supported the belief that discriminative stimulus
      properties of drugs in nonhuman animals correlate highly with subjective effects
      of drugs in humans. In addition to the ability of the drug discrimination
      procedure to measure the subjective effects of drugs, it has a number of other
      strengths that help make it a valuable preclinical assay. (2) Drug discrimination
      can be used for classification of drugs based on shared discriminative stimulus
      properties. (3) The phenomena of tolerance and cross-tolerance can be studied
      with drug discrimination. (4) Discriminative stimulus properties of drugs
      typically have been found to be stereospecific, if a drug is comprised of
      enantiomers. (5) Discriminative stimulus properties of drugs reflect specific CNS
      activity at neurotransmitter receptors. (6) Both human and nonhuman subjects
      display individual differences in their sensitivity to discriminative stimuli and
      drugs. (7) The drug discrimination procedure has been used extensively as a
      preclinical assay in drug development. This chapter is the first in the volume
      The Behavioural Neuroscience of Drug Discrimination, which includes chapters
      concerning the discriminative stimulus properties of various classes of
      psychoactive drugs as well as sections on the applications and approaches for
      using this procedure.

PMID- 29637527
TI  - Subanesthetic Dose Ketamine in Posttraumatic Stress Disorder: A Role for
      Reconsolidation During Trauma-Focused Psychotherapy?
AB  - Despite efforts to develop more effective therapies, PTSD remains a difficult
      disorder to treat. Insight into the dynamic nature of memory formation and its
      required molecular machinery can provide an opportunity to target pathological
      memories for emotionally arousing events. As memories become labile upon
      retrieval, novel information can update the strength and course of these
      consolidated memories. Targeting the process of reconsolidation may offer a
      relevant approach to attenuate fearful and traumatic memories. Specific molecular
      mechanisms that are required for reconsolidation of arousing information include
      an intact functioning of the glutamatergic signaling pathways and, more
      specifically, the integrity of NMDA receptors. Ketamine, a noncompetitive NMDA
      receptor antagonist, is receiving increasing interest for a variety of
      psychiatric indications. This compound can also be an interesting candidate for
      targeting emotional memories. We explore whether single intravenous infusion of a
      subanesthetic dose of ketamine can be considered as a viable augmentation
      strategy for trauma-focused psychotherapy in patients with PTSD. As a
      consequence, a systematic approach is needed to assess the pharmacodynamic
      effects of ketamine in relation to both psychotherapy and its pharmacokinetics
      prior to its application in patient populations. By using a "question-based drug
      development plan," we can explore such aspects for novel drugs, and we formulated
      five additional topics that need to be addressed concerning the psychotherapeutic
      approach and phase orientation of pharmacological assisted psychotherapy.

PMID- 29637528
TI  - Author Correction to: Pooled Analyses of Phase III Studies of ADS-5102
      (Amantadine) Extended-Release Capsules for Dyskinesia in Parkinson's Disease.
AB  - An Online First version of this article was made available online at
      http://link.springer.com/journal/40263/onlineFirst/page/1 on 12 March 2018. An
      error was subsequently identified in the article, and the following correction
      should be noted.

PMID- 29637529
TI  - ND0701, A Novel Formulation of Apomorphine for Subcutaneous Infusion, in
      Comparison to a Commercial Apomorphine Formulation: 28-Day Pharmacokinetic Study
      in Minipigs and a Phase I Study in Healthy Volunteers to Assess the Safety,
      Tolerability, Pharmacokinetics and Relative Bioavailability.
AB  - BACKGROUND: Subcutaneous apomorphine is used for the treatment of Parkinson's
      disease (PD); however, infusion site reactions are a common adverse event (AE),
      which can lead to treatment discontinuation. Apomorphine formulations that are
      more tolerable and convenient for use are needed. OBJECTIVE: Our aim was to
      compare the toxicity and bioavailability of ND0701, a new concentrated
      formulation of apomorphine free base, with one of the commercially available
      apomorphine HCl formulations (APO-go(r), Britannia Pharmaceuticals Ltd). METHODS:
      (1) Preclinical study: 16 minipigs were randomly assigned to placebo, APO-go(r),
      and ND0701 groups, and treated for 28 days. Pharmacokinetic, clinical, and
      pathological assessments were performed. (2) Phase I study: 18 healthy volunteers
      participated in an open-label, two-sequence, randomized, three single-dose,
      partial crossover study to compare the pharmacokinetics, safety, and tolerability
      of ND0701 with APO-go(r) (1%). RESULTS: (1) Preclinical study: No systemic
      toxicity was observed in apomorphine-treated minipigs, but local skin reactions
      were observed at the infusion sites. These effects were less frequent and less
      severe and recovery was more rapid for ND0701 compared with APO-go(r). (2) Phase
      I study: Both formulations were safe and well tolerated under the conditions of
      the study and no severe or serious treatment-emergent AEs were reported. Infusion
      site nodules were reported more frequently, with higher severity, and recovered
      slower at APO-go(r)-treated sites compared with ND0701-treated sites.
      Bioavailability of apomorphine was comparable between the two formulations.
      CONCLUSION: Based on these pilot studies, ND0701 appears to be superior to APO
      go(r) in terms of tolerability and safety, while maintaining comparable
      bioavailability with APO-go(r), and shows promise as a future treatment for PD.

PMID- 29637531
TI  - Erratum to: Visualizing Chemoattraction of Planktonic Cells to a Biofilm.

PMID- 29637530
TI  - The Safety of Second-Generation Antipsychotics During Pregnancy: A Clinically
      Focused Review.
AB  - The issue of antipsychotic treatment during pregnancy is subject to substantial
      uncertainty and some controversy among healthcare providers, specifically
      pertaining to second-generation antipsychotics (SGAs) that are subject to a large
      gap in safety data during pregnancy compared with antidepressants. The amount of
      safety data for the use of SGAs during pregnancy is rapidly increasing, thus
      constantly changing the level of evidence. We performed a clinically focused
      review on the safety of SGA during pregnancy. Twenty-three studies provided
      various pregnancy outcomes for 14,382 pregnant women exposed to an SGA during
      pregnancy. In utero exposure to aripiprazole, olanzapine, and quetiapine is not
      associated with increased risks of major congenital malformations, whereas
      risperidone and paliperidone may be associated with a very minor increased risk
      of congenital malformations. Safety data on ziprasidone and clozapine remain
      scarce and insufficient for a quantitative safety evaluation. No or minimal
      safety data are available for amisulpride, asenapine, lurasidone, and sertindole.
      For other pregnancy outcomes of interest, e.g. miscarriage, stillbirth, and small
      for gestational age, the available data overall do not suggest a clinically
      important increased risk, and do not allow for a meaningful stratification on
      individual drug level. Furthermore, for neonatal adaption and childhood
      neurodevelopment, the data do not allow for a meaningful risk assessment. It is
      imperative that factors in addition to safety data, e.g. individual disease
      history, characteristics and treatment response, adverse reaction profile, and
      patient preferences, be considered for the individual patient when choosing
      specific SGA treatment during pregnancy.

PMID- 29637532
TI  - Giant Pulmonary Hamartoma with Dominant CD34- Positive Smooth Muscle Cell
      Component.
AB  - Pulmonary hamartoma (PH) is usually a solid mass of less than 4 cm in size that
      contains cartilage omponents. A 44-year-old Japanese woman received surgical
      resection of a well-demarcated cystic tumor in the right lung. Resected tissue
      contained a 13 * 10 * 8 cm-sized solid mass with a prominent unilocular cyst (8 *
      6.5 * 5 cm). The tumor was composed of a dominant smooth muscle cell (SMC)
      component with entrapped glandular respiratory epithelium. There was little
      cartilaginous or fatty tissue. Immunohistochemically, SMC was positive for smooth
      muscle actin (SMA) and desmin, as well as CD34. We report a unique case of giant
      pulmonary hamartoma with a dominant CD34 (+) SMC component.

PMID- 29637533
TI  - Epithelial-mesenchymal Transition (EMT) is Correlated with Patient's Prognosis of
      Lung Squamous Cell Carcinoma.
AB  - Epithelial-mesenchymal transition (EMT) is an important step leading to invasion
      and migration of various cancer cells, and are characterized by decreased E
      cadherin as an epithelial marker, and increased vimentin as a mesenchymal marker.
      The present study focused on the clinicopathological significance of E-cadherin
      and vimentin expression in lung squamous cell carcinoma (SqCC).
      Immunohistochemically, E-cadherin expression patterns were classified into two
      types: preserved or reduced; and vimentin expression patterns were also divided
      into two types: positive or negative. The univariate analyses showed six factors
      associated with increased mortality: tumor size (P = 0.031), lymph node
      metastasis (P < 0.001), lymphatic invasion (P < 0.001), histological
      differentiation (P = 0.036), E-cadherin reduced expression (P < 0.001), and
      vimentin positive expression (P = 0.004). Multivariate analysis demonstrated that
      E-cadherin reduced expression (P < 0.001), vimentin positive expression (P =
      0.028), lymph node metastasis (P < 0.001), and age (P = 0.020) were independent
      predictors of patient mortality. There may be some correlation between E-cadherin
      and vimentin expression (P = 0.017), but the correlation coefficient was 0.235.
      The complete EMT and the incomplete EMT type were associated with a poor
      prognosis (p < 0.001 and p=0.036, respectively). The overall survival rate after
      curative resection was significantly lower in patients with the complete EMT type
      (reduced E-cadherin / positive vimentin). In conclusion, both E-cadherin and
      vimentin are independent predictors of mortality, and the EMT phenotype is a
      significant indicator of poor prognosis in lung SqCC.

PMID- 29637534
TI  - Utility of a 3D Roadmap During Balloon-occluded Retrograde Transvenous
      Obliteration for Gastric Varices.
AB  - OBJECTIVE: We describe our initial clinical experience regarding the use of a 3D
      roadmap during balloon-occluded retrograde transvenous obliteration (BRTO) in
      three patients. METHODS: Between June 2016 and July 2016, three BRTO procedures
      were performed in three patients with gastric varices. Preprocedural intravenous
      dynamic CT was performed, and portal venous phase CT images were postprocessed to
      obtain volume rendering (VR) images. A 3D roadmap was developed by overlaying the
      VR images onto the real-time X-ray fluoroscopy images. This 3D roadmap was used
      for interventional guidance during the BRTO procedure. RESULTS: Using a 3D
      roadmap, the catheterization of the gastrorenal shunt was successfully
      accomplished. In addition, in all three patients, the sclerosant could reach the
      gastric varices without the administration of iodinated contrast medium.
      Fluoroscopy time and the iodinated contrast dose administered in the present
      cohort were also substantially lower than in our previous cohorts that did not
      use a 3D roadmap. CONCLUSION: Using a 3D roadmap during BRTO enables easier and
      faster catheter manipulation, thereby helping to reduce both radiation exposure
      and the need to administer iodinated contrast medium.

PMID- 29637535
TI  - Raltegravir-associated Diabetic Ketoacidosis in a Patient with HIV Infection: A
      Case Report.
AB  - Antiretroviral drugs, especially protease inhibitors (PI), are known to induce
      disorders of lipid and glucose metabolism. However, there are only a few reports
      of these side effects in patients treated with integrase strand transfer
      inhibitors (INSTI). We encountered the case of a 46-year-old man who had been
      treated for type 2 diabetes with diet and exercise. He contracted
      immunodeficiency virus (HIV) infection two years earlier and received highly
      active antiretroviral therapy (HAART). Three months before the current admission,
      HAART was switched from a non-nucleic acid reverse transcriptase inhibitor
      (NNRTI) to an INSTI (raltegravir: 800 mg/day). He developed diabetic ketoacidosis
      and was admitted for treatment. The state of health prior to admission was not
      well documented but he showed no clinical signs of acute infection. Accordingly,
      diabetic ketoacidosis was considered to be associated with INSTI. Diabetic
      ketoacidosis was treated appropriately and blood glucose level was controlled
      with medications before discharge from the hospital. Although the present case
      does not provide direct evidence for raltegravir-induced diabetic ketoacidosis,
      we caution physicians about the potential of such side effect associated with the
      use of INSTI.

PMID- 29637536
TI  - Interaction of iNOS Gene (C150T) Polymorphism and Endothelial Dysfunction in
      Pathophysiology of Metabolic Syndrome.
AB  - OBJECTIVE: To study the endothelial dysfunction by measuring Nitric Oxide and
      Endothelin-1, and inter-genotypic variation of inducible Nitric Oxide Synthase
      gene (C150T) polymorphism among the study subjects. METHODS: 50 diagnosed cases
      of metabolic syndrome as per International Diabetes Federation (IDF) criteria and
      50 healthy volunteers as control were enrolled. Nitric Oxide, Endothelin were
      measured and PCR-RFLP was done to identify the iNOS gene C150T polymorphism and
      its effect on serum nitric oxide levels. RESULTS: Subjects with metabolic
      syndrome had lower NO levels (16.3 +/- 10.3 vs 20.9 +/- 11 uM, p = 0.032) and
      higher endothelin (2.68 +/- 1.73 vs 1.98 +/- 0.82 fmol/ml, p = 0.011). The
      frequency of mutant T allele (10% vs 9%) was higher in cases. Serum nitric oxide
      levels were lower in cases expressing the Mutant T allele as compared to wild
      type C allele. However, the differences were not statistically significant.
      CONCLUSIONS: The present study demonstrated that iNOS C150T polymorphism did not
      show significant association with metabolic syndrome. Serum nitric oxide levels
      could be influenced by factors other than genetic polymorphism of iNOS gene
      (C150T) which cause endothelial dysfunction in metabolic syndrome and associated
      co-morbidities.

PMID- 29637537
TI  - Right Aortic Arch with Mirror-image Branching in Adults: Evaluation Using CT.
AB  - OBJECTIVE: We evaluated radiological findings and clinical significance of right
      aortic arch with mirror-image branching (RAMI) in adults using data from computed
      tomography (CT) examinations. MATERIAL AND METHODS: We reviewed recorded reports
      and CT images obtained from university and branch hospitals for RAMI in adults.
      The RAMI incidence in adults found on CT was assessed. Associated congenital and
      acquired cardiovascular diseases were evaluated. RESULTS: A total of 27 cases (14
      men, 13 women; mean age, 59.4 +/- 18.3 years) of RAMI were found. Among 107,014
      cases in three hospitals, the RAMI incidence in the first, second, and third
      Tokai University hospitals were 0.018%, 0.012%, and 0.012%, respectively. Eight
      cases had high aortic arches and four cases had aortic diverticulum (AD) in
      proximal descending aorta. Three cases had a history of tetralogy of Fallot. One
      case with an absent left pulmonary artery and three cases with an aberrant left
      brachiocephalic vein were found incidentally. Two cases were associated with AD
      aneurysm and vascular ring formation. One case had stenosis of the left
      subclavian artery due to injury. CONCLUSION: Cases of RAMI found in CT
      examinations in adults were extremely rare. Some cases were associated with
      congenital anomalies and/or acquired cardiovascular disease.

PMID- 29637539
TI  - Are rates of species diversification and body size evolution coupled in the
      ferns?
AB  - PREMISE OF THE STUDY: Understanding the relationship between phenotypic evolution
      and lineage diversification is a central goal of evolutionary biology. To extend
      our understanding of the role morphological evolution plays in the
      diversification of plants, we examined the relationship between leaf size
      evolution and lineage diversification across ferns. METHODS: We tested for an
      association between body size evolution and lineage diversification using a
      comparative phylogenetic approach that combined a time-calibrated phylogeny and
      leaf size data set for 2654 fern species. Rates of leaf size change and lineage
      diversification were estimated using BAMM, and rate correlations were performed
      for rates obtained for all families and individual species. Rates and patterns of
      rate-rate correlation were also analyzed separately for terrestrial and epiphytic
      taxa. KEY RESULTS: We find no significant correlation between rates of leaf area
      change and lineage diversification, nor was there a difference in this pattern
      when growth habit is considered. Our results are consistent with the findings of
      an earlier study that reported decoupled rates of body size evolution and
      diversification in the Polypodiaceae, but conflict with a recent study that
      reported a positive correlation between body size evolution and lineage
      diversification rates in the tree fern family Cyatheaceae. CONCLUSIONS: Our
      findings indicate that lineage diversification in ferns is largely decoupled from
      shifts in body size, in contrast to several other groups of organisms. Speciation
      in ferns appears to be primarily driven by hybridization and isolation along
      elevational gradients, rather than adaptive radiations featuring prominent
      morphological restructuring. The exceptional diversity of leaf morphologies in
      ferns appears to reflect a combination of ecophysiological constraints and
      adaptations that are not key innovations.

PMID- 29637538
TI  - Hyperbaric oxygenation for tumour sensitisation to radiotherapy.
AB  - BACKGROUND: Cancer is a common disease and radiotherapy is one well-established
      treatment for some solid tumours. Hyperbaric oxygenation therapy (HBOT) may
      improve the ability of radiotherapy to kill hypoxic cancer cells, so the
      administration of radiotherapy while breathing hyperbaric oxygen may result in a
      reduction in mortality and recurrence. OBJECTIVES: To assess the benefits and
      harms of administering radiotherapy for the treatment of malignant tumours while
      breathing HBO. SEARCH METHODS: In September 2017 we searched the Cochrane Central
      Register of Controlled Trials (CENTRAL), the Cochrane Library Issue 8, 2017,
      MEDLINE, Embase, and the Database of Randomised Trials in Hyperbaric Medicine
      using the same strategies used in 2011 and 2015, and examined the reference lists
      of included articles. SELECTION CRITERIA: Randomised and quasi-randomised studies
      comparing the outcome of malignant tumours following radiation therapy while
      breathing HBO versus air or an alternative sensitising agent. DATA COLLECTION AND
      ANALYSIS: Three review authors independently evaluated the quality of and
      extracted data from the included trials. MAIN RESULTS: We included 19 trials in
      this review (2286 participants: 1103 allocated to HBOT and 1153 to control).For
      head and neck cancer, there was an overall reduction in the risk of dying at both
      one year and five years after therapy (risk ratio (RR) 0.83, 95% confidence
      interval (CI) 0.70 to 0.98, number needed to treat for an additional beneficial
      outcome (NNTB) = 11 and RR 0.82, 95% CI 0.69 to 0.98, high-quality evidence), and
      some evidence of improved local tumour control immediately following irradiation
      (RR with HBOT 0.58, 95% CI 0.39 to 0.85, moderate-quality evidence due to
      imprecision). There was a lower incidence of local recurrence of tumour when
      using HBOT at both one and five years (RR at one year 0.66, 95% CI 0.56 to 0.78,
      high-quality evidence; RR at five years 0.77, 95% CI 0.62 to 0.95, moderate
      quality evidence due to inconsistency between trials). There was also some
      evidence with regard to the chance of metastasis at five years (RR with HBOT 0.45
      95% CI 0.09 to 2.30, single trial moderate quality evidence imprecision). No
      trials reported a quality of life assessment. Any benefits come at the cost of an
      increased risk of severe local radiation reactions with HBOT (severe radiation
      reaction RR 2.64, 95% CI 1.65 to 4.23, high-quality evidence). However, the
      available evidence failed to clearly demonstrate an increased risk of seizures
      from acute oxygen toxicity (RR 4.3, 95% CI 0.47 to 39.6, moderate-quality
      evidence).For carcinoma of the uterine cervix, there was no clear benefit in
      terms of mortality at either one year or five years (RR with HBOT at one year
      0.88, 95% CI 0.69 to 1.11, high-quality evidence; RR at five years 0.95, 95% CI
      0.80 to 1.14, moderate-quality evidence due to inconsistency between trials).
      Similarly, there was no clear evidence of a benefit of HBOT in the reported rate
      of local recurrence (RR with HBOT at one year 0.82, 95% CI 0.63 to 1.06, high
      quality evidence; RR at five years 0.85, 95% CI 0.65 to 1.13, moderate-quality
      evidence due to inconsistency between trials). We also found no clear evidence
      for any effect of HBOT on the rate of development of metastases at both two years
      and five years (two years RR with HBOT 1.05, 95% CI 0.84 to 1.31, high quality
      evidence; five years RR 0.79, 95% CI 0.50 to 1.26, moderate-quality evidence due
      to inconsistency). There were, however, increased adverse effects with HBOT. The
      risk of a severe radiation injury at the time of treatment with HBOT was 2.05,
      95% CI 1.22 to 3.46, high-quality evidence. No trials reported any failure of
      local tumour control, quality of life assessments, or the risk of seizures during
      treatment.With regard to the treatment of urinary bladder cancer, there was no
      clear evidence of a benefit in terms of mortality from HBOT at one year (RR 0.97,
      95% CI 0.74 to 1.27, high-quality evidence), nor any benefit in the risk of
      developing metastases at two years (RR 2.0, 95% CI 0.58 to 6.91, moderate-quality
      evidence due to imprecision). No trial reported on failure of local control,
      local recurrence, quality of life, or adverse effects.When all cancer types were
      combined, there was evidence for an increased risk of severe radiation tissue
      injury during the course of radiotherapy with HBOT (RR 2.35, 95% CI 1.66 to 3.33,
      high-quality evidence) and of oxygen toxic seizures during treatment (RR with
      HBOT 6.76, 96% CI 1.16 to 39.31, moderate-quality evidence due to imprecision).
      AUTHORS' CONCLUSIONS: We found evidence that HBOT improves local tumour control,
      mortality, and local tumour recurrence for cancers of the head and neck. These
      benefits may only occur with unusual fractionation schemes. Hyperbaric
      oxygenation therapy is associated with severe tissue radiation injury. Given the
      methodological and reporting inadequacies of the included studies, our results
      demand a cautious interpretation. More research is needed for head and neck
      cancer, but is probably not justified for uterine cervical or bladder cancer.
      There is little evidence available concerning malignancies at other anatomical
      sites.

PMID- 29637540
TI  - Associations of Number Line Estimation With Mathematical Competence: A Meta
      analysis.
AB  - The number line estimation task is widely used to investigate mathematical
      learning and development. The present meta-analysis statistically synthesized the
      extensive evidence on the correlation between number line estimation and broader
      mathematical competence. Averaged over 263 effect sizes with 10,576 participants
      with sample mean ages from 4 to 14 years, this correlation was r = .443. The
      correlation increased with age, mainly because it was higher for fractions than
      for whole numbers. The correlation remained stable across a wide range of task
      variants and mathematical competence measures (i.e., counting, arithmetic, school
      achievement). These findings demonstrate that the task is a robust tool for
      diagnosing and predicting broader mathematical competence and should be further
      investigated in developmental and experimental training studies.

PMID- 29637541
TI  - How we manage patients with Waldenstrom macroglobulinaemia.
AB  - Waldenstrom macroglobulinaemia (WM) is a rare, indolent B-cell
      lymphoproliferative disorder characterized by cellular involvement in bone marrow
      and monoclonal IgM production. Symptoms can be related to cytopenias, tumoural
      involvement, or IgM-related disorders. Somatic mutations in the MYD88 gene have
      been described in the majority of WM cases. The mutation is responsible for a
      gain-of-function and induces activation of nuclear factor-kappaB, for DNA
      transcription and cell survival. It seems that MYD88 mutation is associated with
      better prognosis and better response to some treatment. Treatments are started
      when WM is symptomatic, following systematic biological and morphological
      assessments. Therapeutic choice depends on age, frailty and urgent efficacy need.
      In first line, the majority of patients are treated with monoclonal anti-CD20
      antibody-based regimens combined with cytotoxic chemotherapy. Rituximab,
      cyclophosphamide and dexamethasone remain the most commonly used regimen with
      good safety. Nevertheless, increasing numbers of new drugs are becoming available
      or are in development. Proteasome inhibitors, such as bortezomib or carfilzmib,
      showed good and rapid responses. Bruton tyrosine kinase (BTK) inhibitor
      demonstrated excellent results and is now available for relapse/refractory
      disease or as first line for some patients. This review highlights the diagnostic
      procedures and therapeutic approaches in WM.

PMID- 29637542
TI  - Risk-Benefit Assessment of Ethinylestradiol Using a Physiologically Based
      Pharmacokinetic Modeling Approach.
AB  - Current formulations of combined oral contraceptives (COC) containing
      ethinylestradiol (EE) have <=35 MUg due to increased risks of cardiovascular
      diseases (CVD) with higher doses of EE. Low-dose formulations however, have
      resulted in increased incidences of breakthrough bleeding and contraceptive
      failure, particularly when coadministered with inducers of cytochrome P450
      enzymes (CYP). The developed physiologically based pharmacokinetic model
      quantitatively predicted the effect of CYP3A4 inhibition and induction on the
      pharmacokinetics of EE. The predicted Cmax and AUC ratios when coadministered
      with voriconazole, fluconazole, rifampicin, and carbamazepine were within 1.25 of
      the observed data. Based on published clinical data, an AUCss value of 1,000
      pg/ml.h was selected as the threshold for breakthrough bleeding. Prospective
      application of the model in simulations of different doses of EE (20 MUg, 35 MUg,
      and 50 MUg) identified percentages of the population at risk of breakthrough
      bleeding alone and with varying degrees of CYP modulation.

PMID- 29637545
TI  - Erratum.

PMID- 29637543
TI  - Dopamine-Related Genotypes and Physical Activity Change During an Intervention:
      The Lifestyle Interventions and Independence for Elders Study.
AB  - OBJECTIVES: To determine whether intervention-induced physical activity (PA)
      changes in sedentary older adults differed according to dopamine-related
      genotype. DESIGN: Randomized clinical trial (Lifestyle Interventions and
      Independence for Elders Trial (2010-13)). SETTING: Multicenter study, 8 U.S.
      LOCATIONS:  PARTICIPANTS: Volunteer sample of sedentary adults aged 70 to 89 at
      risk of disability (N=1635). INTERVENTIONS: Structured PA versus health education
      (HE) for an average of 2.6 years. MEASUREMENTS: Single-nucleotide polymorphisms
      of dopamine-related genes (dopamine receptor (DR) D1, DRD2, DRD3, and catechol-O
      methyltransferase (COMT)) were assessed. Average moderate to vigorous PA (MVPA)
      was calculated using accelerometry (min/d) at baseline and 6, 12, and 24 months.
      Between-arm MVPA differences according to genotype and genotype with square root
      transformed MVPA separately according to arm were tested, stratified according to
      race, and adjusted for multiple comparisons. RESULTS: White participants in the
      PA arm (n=513) had higher average square root transformed MVPA (4.91+/-1.91)than
      those in the HE arm (n=538) (4.51+/-1.82) (p=.001). Between-arm differences were
      greater for DRD2 Met/Met (high dopamine; HE: 4.76+/-1.80, PA: 5.53+/-1.60, p=.03)
      than Val/Val (low dopamine; HE: 4.58+/-1.92, PA: 4.81+/-1.83, p=.16); results
      were similar for COMT. In the PA arm, DRD2 Met/Met was associated with higher
      average MVPA (5.39+/-2.00) than Met/Val (4.46+/-2.51) (p=.01) and Val/Val (4.65+/
      2.71) (p=.01). There were no associations for other genes. Associations were not
      significant in blacks but followed similar trends. CONCLUSION: Higher dopamine
      signaling may support changes in PA during an intervention. The role of dopamine
      related pathways in promoting PA participation and enhancing response to
      interventions in sedentary older adults should be studied. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT01072500.

PMID- 29637546
TI  - Comorbidity of mental and physical disorders: a key problem for medicine in the
      21st century.

PMID- 29637544
TI  - Longitudinal Relationship Between Hearing Aid Use and Cognitive Function in Older
      Americans.
AB  - OBJECTIVES: To test whether hearing aid use alters cognitive trajectories in
      older adults. DESIGN: US population-based longitudinal cohort study SETTING: Data
      were drawn from the Health and Retirement Study (HRS), which measured cognitive
      performance repeatedly every 2 years over 18 years (1996-2014). PARTICIPANTS:
      Adults aged 50 and older who who took part in a minimum of 3 waves of the HRS and
      used hearing aids for the first time between Waves 4 and 11 (N=2,040).
      MEASUREMENTS: Cognitive outcomes were based on episodic memory scores determined
      according to the sum of immediate and delayed recall of 10 words. RESULTS:
      Hearing aid use was positively associated with episodic memory scores (beta=1.53,
      p<.001). Decline in episodic memory scores was slower after (beta=-0.02, p<.001)
      than before using hearing aids (beta=-0.1, p<.001). These results were robust to
      adjustment for multiple confounders and to attrition, as accounted for using a
      joint model. CONCLUSIONS: Hearing aids may have a mitigating effect on
      trajectories of cognitive decline in later life. Providing hearing aids or other
      rehabilitative services for hearing impairment much earlier in the course of
      hearing impairment may stem the worldwide rise of dementia.

PMID- 29637547
TI  - Religiosity and psychotic experiences.

PMID- 29637548
TI  - Repeated sleep deprivation for a more rapid decrease in depressive symptoms in
      combined chronotherapy?

PMID- 29637549
TI  - Automated detection of focal cortical dysplasia type II with surface-based
      magnetic resonance imaging postprocessing and machine learning.
AB  - OBJECTIVE: Focal cortical dysplasia (FCD) is a major pathology in patients
      undergoing surgical resection to treat pharmacoresistant epilepsy. Magnetic
      resonance imaging (MRI) postprocessing methods may provide essential help for
      detection of FCD. In this study, we utilized surface-based MRI morphometry and
      machine learning for automated lesion detection in a mixed cohort of patients
      with FCD type II from 3 different epilepsy centers. METHODS: Sixty-one patients
      with pharmacoresistant epilepsy and histologically proven FCD type II were
      included in the study. The patients had been evaluated at 3 different epilepsy
      centers using 3 different MRI scanners. T1-volumetric sequence was used for
      postprocessing. A normal database was constructed with 120 healthy controls. We
      also included 35 healthy test controls and 15 disease test controls with
      histologically confirmed hippocampal sclerosis to assess specificity. Features
      were calculated and incorporated into a nonlinear neural network classifier,
      which was trained to identify lesional cluster. We optimized the threshold of the
      output probability map from the classifier by performing receiver operating
      characteristic (ROC) analyses. Success of detection was defined by overlap
      between the final cluster and the manual labeling. Performance was evaluated
      using k-fold cross-validation. RESULTS: The threshold of 0.9 showed optimal
      sensitivity of 73.7% and specificity of 90.0%. The area under the curve for the
      ROC analysis was 0.75, which suggests a discriminative classifier. Sensitivity
      and specificity were not significantly different for patients from different
      centers, suggesting robustness of performance. Correct detection rate was
      significantly lower in patients with initially normal MRI than patients with
      unequivocally positive MRI. Subgroup analysis showed the size of the training
      group and normal control database impacted classifier performance. SIGNIFICANCE:
      Automated surface-based MRI morphometry equipped with machine learning showed
      robust performance across cohorts from different centers and scanners. The
      proposed method may be a valuable tool to improve FCD detection in presurgical
      evaluation for patients with pharmacoresistant epilepsy.

PMID- 29637550
TI  - Treatment of acute lymphoblastic leukaemia with the second generation of CD19 CAR
      T containing either CD28 or 4-1BB.
AB  - T cells modified with anti-CD19 chimeric antigen receptor (CAR) containing either
      CD28 or 4-1BB (also termed TNFRSF9, CD137) costimulatory signalling have shown
      great potential in the treatment of acute lymphoblastic leukaemia (ALL). However,
      the difference between CD28 and 4-1BB costimulatory signalling in CAR-T treatment
      has not been well elucidated in clinical trials. In this study, we treated 10
      relapsed or refractory ALL patients with the second generation CD19 CAR-T. The
      first 5 patients were treated with CD28-CAR and the other 5 patients were treated
      with 4-1BB CAR-T. All the 10 patients were response-evaluable. Three patients
      achieved complete remission and 1 patient with extramedullary disease achieved
      partial response after CD28-CAR-T treatment. In the 4-1BB CAR-T treatment group,
      3 patients achieved complete remission. Furthermore, FLT-3 ligand (FLT3LG) was
      highly correlated with response time and may serve as a prognosis factor. No
      severe adverse events were observed in these 10 treated patients. Our study
      showed that both CD28 CAR-T and 4-1BB CAR-T both worked for response but they
      differed in response pattern (peak reaction time, reaction lasting time and
      reaction degree), adverse events, cytokine secretion and immune-suppressive
      factor level.

PMID- 29637551
TI  - The primary prevention of epilepsy: A report of the Prevention Task Force of the
      International League Against Epilepsy.
AB  - Among the causes of epilepsy are several that are currently preventable. In this
      review, we summarize the public health burden of epilepsy arising from such
      causes and suggest priorities for primary epilepsy prevention. We conducted a
      systematic review of published epidemiologic studies of epilepsy of 4 preventable
      etiologic categories-perinatal insults, traumatic brain injury (TBI), central
      nervous system (CNS) infection, and stroke. Applying consistent criteria, we
      assessed the quality of each study and extracted data on measures of risk from
      those with adequate quality ratings, summarizing findings across studies as
      medians and interquartile ranges. Among higher-quality population-based studies,
      the median prevalence of active epilepsy across all ages was 11.1 per 1000
      population in lower- and middle-income countries (LMIC) and 7.0 per 1000 in high
      income countries (HIC). Perinatal brain insults were the largest attributable
      fraction of preventable etiologies in children, with median estimated fractions
      of 17% in LMIC and 15% in HIC. Stroke was the most common preventable etiology
      among older adults with epilepsy, both in LMIC and in HIC, accounting for half or
      more of all new onset cases. TBI was the attributed cause in nearly 5% of
      epilepsy cases in HIC and LMIC. CNS infections were a more common attributed
      cause in LMIC, accounting for about 5% of all epilepsy cases. Among some rural
      LMIC communities, the median proportion of epilepsy cases attributable to endemic
      neurocysticercosis was 34%. A large proportion of the overall public health
      burden of epilepsy is attributable to preventable causes. The attributable
      fraction for perinatal causes, infections, TBI, and stroke in sum reaches nearly
      25% in both LMIC and HIC. Public health interventions addressing maternal and
      child health care, immunizations, public sanitation, brain injury prevention, and
      stroke prevention have the potential to significantly reduce the burden of
      epilepsy.

PMID- 29637552
TI  - Use of the 50-g glucose challenge test to predict excess delivery weight.
AB  - OBJECTIVE: To identify a cut-off value for the 50-g glucose challenge test (GCT)
      that predicts excess delivery weight. METHODS: A retrospective study was
      conducted among pregnant women who undertook a 50-g GCT at Hacettepe University
      Hospital, Ankara, Turkey, between January 1, 2000, and December 31, 2016.
      Patients with singleton pregnancies who delivered live neonates after 28 weeks of
      pregnancy were included. Patients were classified according to their 50-g GCT
      values into group 1 (<7.770 mmol/L); group 2 (7.770 to <8.880 mmol/L, group 3
      (8.880-9.990 mmol/L); or group 4 (>9.990 mmol/L). Classification and regression
      tree data mining was performed to identify the 50-g GCT cut-off value
      corresponding to a substantial increase in delivery weight. , RESULTS: Median
      delivery weight were 3100 g in group 1 (n=352), 3200 g in group 2 (n=165), 3720 g
      in group 3 (n=47), and 3865 g in group 4 (n=20). Gravidity, 50-g GCT value, and
      pregnancy duration at delivery explained 30.6% of the observed variance in
      delivery weight. The cut-off required for maternal blood glucose level to predict
      excessive delivery weight was 8.741 mmol/L. CONCLUSION: The 50-g GCT can be used
      to identify women at risk of delivering offspring with excessive delivery weight.

PMID- 29637553
TI  - The Health Risks of Belgian Illicit Indoor Cannabis Plantations.
AB  - We assessed the prevalence of potential health hazards to intervention staff and
      cannabis growers in Belgian indoor cannabis plantations. Surface mold swab
      samples were taken at 16 Belgian indoor plantations contained mostly Penicillium
      sp. and Aspergillus sp. However, their precise health impact on intervention
      staff and illicit growers is unclear as no molds spore concentrations were
      measured. Atmospheric gas monitoring in the studied cannabis plantations did not
      reveal dangerous toxic substances. Health symptoms were reported by 60% of 221
      surveyed police, but could not be linked to specific plantation characteristics.
      We conclude that Belgian indoor cannabis plantations pose a potential health
      threat to growers and intervention staff. AS there are currently no clear safety
      guidelines for seizure and dismantling of Belgian indoor cannabis plantations, we
      recommend first responders to follow strict safety rules when entering the growth
      rooms, which include wearing appropriate personal protective equipment.

PMID- 29637554
TI  - Bre1 mediates the ubiquitination of histone H2B by regulating Lge1 stability.
AB  - Histone H2B ubiquitination mediated by the Rad6/Bre1 complex is crucial for
      regulating the stability and reassembly of the nucleosome. To understand the
      regulatory mechanisms of H2B ubiquitination, we explored proteins related to the
      Rad6/Bre1 complex. Interestingly, we observed that the stability of Lge1,
      reported to be a cofactor of Bre1, is greatly reduced in the absence of Bre1. The
      stability of Lge1 did require the middle fragment of Bre1 containing a coiled
      coil structure, but not its E3 ligase activity. Additionally, we found that Lge1
      is involved in the 'writing' step of H2B ubiquitination. Our data suggest that
      Bre1 mediates H2B ubiquitination more precisely by maintaining the stability of
      Lge1 as well as through its role as a known E3 ligase.

PMID- 29637555
TI  - Nonconvulsive status epilepticus in rats leads to brain pathology.
AB  - OBJECTIVE: Status epilepticus (SE) is an abnormally prolonged epileptic seizure
      that if associated with convulsive motor symptoms is potentially life threatening
      for a patient. However, 20%-40% of patients with SE lack convulsive events and
      instead present with more subtle semiology such as altered consciousness and less
      motor activity. Today, there is no general consensus regarding to what extent
      nonconvulsive SE (NCSE) is harmful to the brain, which adds uncertainty to
      stringent treatment regimes. METHODS: Here, we evaluated brain pathology in an
      experimental rat and mouse model of complex partial NCSE originating in the
      temporal lobes with Western blot analysis, immunohistochemistry, and ex vivo
      diffusion tensor imaging (DTI). The NCSE was induced by electrical stimulation
      with intrahippocampal electrodes and terminated with pentobarbital anesthesia.
      Video-electroencephalographic recordings were performed throughout the
      experiment. RESULTS: DTI of mice 7 weeks post-NCSE showed no robust long-lasting
      changes in fractional anisotropy within the hippocampal epileptic focus. Instead,
      we found pathophysiological changes developing over time when measuring protein
      levels and cell counts in extracted brain tissue. At 6 and 24 hours post-NCSE in
      rats, few changes were observed within the hippocampus and cortical or
      subcortical structures in Western blot analyses of key components of the cellular
      immune response and synaptic protein expression, while neurodegeneration had
      started. However, 1 week post-NCSE, both excitatory and inhibitory synaptic
      protein levels were decreased in hippocampus, concomitant with an excessive
      microglial and astrocytic activation. At 4 weeks, a continuous immune response in
      the hippocampus was accompanied with neuronal loss. Levels of the excitatory
      synaptic adhesion molecule N-cadherin were decreased specifically in rats that
      developed unprovoked spontaneous seizures (epileptogenesis) within 1 month
      following NCSE, compared to rats only exhibiting acute symptomatic seizures
      within 1 week post-NCSE. SIGNIFICANCE: These findings provide evidence for a
      significant brain pathology following NCSE in an experimental rodent model.

PMID- 29637556
TI  - 1800 MHz mobile phone irradiation induced oxidative and nitrosative stress leads
      to p53 dependent Bax mediated testicular apoptosis in mice, Mus musculus.
AB  - Present study was carried out to investigate the effect of long-term mobile phone
      radiation exposure in different operative modes (Dialing, Receiving, and Stand
      by) on immature male mice. Three-week old male mice were exposed to mobile phone
      (1800 MHz) radiation for 3 hr/day for 120 days in different operative modes. To
      check the changes/alteration in testicular histoarchitecture and serum
      testosterone level, HE staining and ELISA was performed respectively. Further, we
      have checked the redox status (ROS, NO, MDA level, and antioxidant enzymes: SOD,
      CAT, and GPx) by biochemical estimation, alteration in the expression of pro
      apoptotic proteins (p53 and Bax), active executioner caspase-3, full
      length/uncleaved PARP-1 (DNA repair enzyme), anti-apoptotic proteins (Bcl-2 and
      Bcl-xL ) in testes by immunofluorescence and cytosolic cytochrome-c by Western
      blot. Decreased seminiferous tubule diameter, sperm count, and viability along
      with increased germ cells apoptosis and decreased serum testosterone level, was
      observed in the testes of all the mobile phone exposed mice compared with
      control. We also observed that, mobile phone radiation exposure in all the three
      different operative modes alters the testicular redox status via increasing ROS,
      NO, and MDA level, and decreasing antioxidant enzymes levels leading to enhanced
      apoptosis of testicular cells by increasing the expression of pro-apoptotic and
      apoptotic proteins along with decreasing the expression of anti-apoptotic
      protein. On the basis of results, it is conclude that long-term mobile phone
      radiation exposure induced oxidative stress leads to apoptosis of testicular
      cells and thus impairs testicular function.

PMID- 29637557
TI  - Is the tilt of the lipid head group correlated with the number of intermolecular
      interactions at the bilayer interface?
AB  - Lipid and water molecules comprising the bilayer form an integral entity owing to
      only weak physical interactions. At the bilayer interface, these interactions
      chiefly involve hydrogen bonding and charge pairing. Lipid head groups make
      hydrogen bonds (H-bonds) predominantly with water, whereas interlipid H-bonds and
      charge pairs are less numerous. Both interlipid H-bonding and charge pairing
      depend on the distance and relative orientation of the interacting head groups.
      In this computational paper, correlations are analysed between the orientation of
      the lipid head group and the number of interlipid interactions at the interface
      of a bilayer made of galactolipids, forming direct interlipid H-bonds, and of
      phosphatidylcholines forming interlipid charge pairs. The correlations are not
      strong, however, in both bilayers they show a similar trend.

PMID- 29637558
TI  - Non-fluorescent mutant of green fluorescent protein sheds light on the mechanism
      of chromophore formation.
AB  - The mechanism of green fluorescent protein (GFP) chromophore formation is still
      not clearly defined. Two mechanisms have been proposed: cyclisation-dehydration
      oxidation (Mechanism A) and cyclisation-oxidation-dehydration (Mechanism B). To
      distinguish between these mechanisms, we generated a non-fluorescent mutant of
      GFP, S65T/G67A-GFP. This mutant folds to a stable, native-like structure but
      lacks fluorescence due to interruption of the chromophore maturation process.
      Mass spectrometric analysis of peptides derived from this mutant reveal that
      chromophore formation follows only mechanism A, but that the final oxidation
      reaction is suppressed. This result is unexpected within the pool of examined GFP
      mutants, since for the wild-type GFP, there is strong support for mechanism B.

PMID- 29637559
TI  - Low-grade squamous intraepithelial lesions among women with HIV.
AB  - OBJECTIVES: To assess whether women with HIV who had low-grade squamous
      intraepithelial lesions (LSIL) on cytology had cervical disease. METHODS: The
      present retrospective cross-sectional study included data from women with LSIL
      who attended a tertiary hospital in South Africa between April 1, 2003, and
      December 31, 2013. Patient information was extracted from a colposcopy database.
      RESULTS: The study included 652 patients. The median age was 36 years
      (interquartile range [IQR] 31-42 years; range 18-66 years) and the median parity
      was three (IQR 2-5; range 0-10). In all, 266 (40.8%) women had a histology result
      of HPV or cervical intraepithelial neoplasia 1 (CIN1); 386 (59.2%) had a
      histology result of CIN2 or higher. The median cluster of differentiation 4 (CD4)
      count was 275.00 cells/mm3 (IQR 173.50-434.00 cells/mm3 ; range 2-1211 cells/mm3
      ). A total of 312 (47.9%) women were using antiretroviral therapy. Use of
      antiretroviral therapy (unadjusted odds ratio 0.57; P=0.001) and a CD4 count of
      at least 200 cells/mm3 (unadjusted odds ratio 0.81; P=0.002) were associated with
      a histology result of HPV or CIN1. CONCLUSION: Most of the women with a cytology
      report of LSIL had CIN2 or higher, suggesting that the practice of referral for
      colposcopy should continue.

PMID- 29637560
TI  - Endometrial cancer after endometrial ablation or resection for menorrhagia.
AB  - OBJECTIVE: To assess the incidence of endometrial cancer after endometrial
      ablation or resection (EA/R) for menorrhagia. METHOD: The present retrospective
      observational cohort study included women who underwent EA/R for menorrhagia at
      Aberdeen Royal Infirmary between February 1, 1990 and December 31, 1997. Follow
      up data until 2015 were examined. To assess risk of endometrial cancer, each
      woman was matched by age to the annual observed incidence of endometrial cancer
      in northeast Scotland for each year from the date of EA/R until 2015. RESULTS:
      During the 7-year study period, 901 eligible women (mean age 42.3 +/- 5.7 years;
      range 26-50 years) underwent EA/R. Of these patients, 204 (22.6%) subsequently
      had a hysterectomy for reasons other than endometrial cancer, and 695 (77.1%) did
      not. The overall incidence of endometrial cancer was 0.2% (2/901); the risk of
      developing endometrial cancer after EA/R was calculated as 11.1 per 100 000 women
      years. The mean expected incidence for all women and the subgroup with no
      hysterectomy was estimated to be 26.5 and 35.6 occurrences per 100 000 women
      years, respectively. The observed incidence was significantly lower versus the
      mean expected risk for both groups (P<0.001). CONCLUSION: The findings indicate
      that the risk of endometrial cancer could be significantly reduced but not
      eliminated by EA/R.

PMID- 29637561
TI  - 1,25-dihydroxyvitamin D deficiency accelerates alveolar bone loss independent of
      aging and extracellular calcium and phosphorus.
AB  - BACKGROUND: Vitamin D is critical for bone homeostasis and immunomodulation. We
      therefore assessed whether 1,25-dihydroxyvitamin D (1,25(OH)2 D) deficiency in
      mice with targeted deletion of the gene encoding 25-hydroxyvitamin D-1alpha
      hydroxylase (1alpha(OH)ase [1alphaOH)ase-/- mice]) results in alveolar bone loss
      and periodontal inflammation in vivo. METHODS: Ten-week-old and 12-month-old
      1alpha(OH)ase-/- mice and wild-type littermates were fed a normal diet or a
      rescue diet, and the phenotype of the periodontium was then analyzed using
      microcomputed tomography, histology, immunohistochemistry, and real-time Reverse
      transcription-polymerase chain reaction (RT-PCR). RESULTS: Alveolar bone loss was
      increased and maxillary bone mineral density (BMD), osteoblast numbers, and the
      number of osterix-positive cells were decreased significantly in 1alpha(OH)ase-/-
      mice compared with wild-type mice. Although aging from 10 weeks to 12 months
      accentuated these changes, and a rescue diet reduced them, the alterations in the
      1alpha(OH)ase-/- mice exceeded the effects of aging and diet change. Nuclear
      factor kappa light-chain-enhancer of activated B cells (NF-kB) p65 and CD3
      positive cells, and the gene expression levels of interleukin (IL)-1beta, tumor
      necrosis factor (TNF)-alpha, matrix metalloproteinase (MMP)-3 and -8 were all
      increased significantly in periodontal tissues of 1alpha(OH)ase-/- mice compared
      with wild-type mice. Aging from 10 weeks to 12 months also accentuated these
      changes, and a rescue diet reduced them, however, the alterations in the
      1alpha(OH)ase-/- mice exceeded the effects of aging and diet change. CONCLUSION:
      1,25(OH)2 D deficiency in the 1alpha(OH)ase-/- mice accelerated alveolar bone
      loss by inhibiting osteoblastic bone formation and enhancing periodontal tissue
      degeneration in a calcium- and phosphorus- as well as an age-independent manner.

PMID- 29637562
TI  - A Fatal Case of Gas Intoxication in Silage Pit.
AB  - Fatalities due to gas intoxication are rare in routine forensic casework. The
      most common gas is carbon monoxide, with other gases (ammonia, methane, propane
      and butane, carbon dioxide, hydrogen sulfide) encountered only very rarely. In
      this report, we describe the accidental death of two maintenance workers who were
      found in the silage pit at a biogas plant. The autopsy revealed signs of asphyxia
      in both the deceased. Analysis of the gaseous mixtures in the tank using an
      infrared gas analyzer showed slightly elevated concentrations of carbon dioxide.
      Toxicological examination of the blood of both the deceased using gas
      chromatography with a flame ionization detector, spectrophotometry and liquid
      chromatography-mass spectrometry did not detect any toxicologically significant
      substance that would explain the sudden collapse. Both the autopsy and the
      toxicology analyses suggest CO2 intoxication as the most likely cause for the
      collapse of the two men, which then led to sudden asphyxia.

PMID- 29637563
TI  - Forensic SNP Genotyping with SNaPshot: Development of a Novel In-house SBE
      Multiplex SNP Assay.
AB  - This study introduces a newly developed in-house SNaPshot single-base extension
      (SBE) multiplex assay for forensic single nucleotide polymorphism (SNP)
      genotyping of fresh and degraded samples. The assay was validated with fresh
      blood samples from four different populations. In addition, altogether 24 samples
      from skeletal remains were analyzed with the multiplex. Full SNP profiles could
      be obtained from 14 specimens, while ten remains showed partial SNP profiles.
      Minor allele frequencies (MAF) of bone samples and different populations were
      compared and used for association of skeletal remains with a certain population.
      The results reveal that the SNPs of the bone samples are genetically close to the
      Pathan population. The findings show that the new multiplex system can be
      utilized for SNP genotyping of degraded and forensic relevant skeletal material,
      enabling to provide additional investigative leads in criminal cases.

PMID- 29637564
TI  - Retronasal olfaction in chronic rhinosinusitis.
AB  - OBJECTIVE: The goals of this study were to assess retronasal olfaction in
      patients with chronic rhinosinusitis (CRS) and describe clinical factors that
      influence retronasal olfaction. This study sought to investigate the influence of
      retronasal olfaction on patient-perceived outcomes and examine the relationship
      between retronasal and orthonasal olfaction. METHODS: Retronasal olfactory
      function was tested using odorized powders in the oral cavity, whereas Sniffin'
      Sticks test (Burghart Instruments, Wedel, Germany) were used to assess orthonasal
      function prospectively in 69 adult CRS patients. Endoscopic evaluation of the
      olfactory cleft was scored using the Olfactory Cleft Endoscopy Scale (OCES).
      Several quality-of-life (QOL) instruments relating to sinonasal, olfactory, and
      chemosensory functions were used to assess the interactions between patient
      reported outcome measures and retronasal olfaction. RESULTS: There was strong
      correlation between retronasal and total orthonasal olfaction scores (r = 0.77, P
      < 0.001) as well as retronasal scores with orthonasal subscores. Retronasal
      scores were worse in patients with nasal polyposis (P = 0.002), asthma (P =
      0.04), and aspirin-exacerbated respiratory disease (AERD) (P = 0.02), whereas
      OCES was the only independent predictor of retronasal olfaction (r = -0.42, P <
      0.001). Significant correlation existed between retronasal olfaction and
      olfactory-specific QOL and chemosensory smell scores. CONCLUSION: Few studies
      have examined retronasal olfaction in CRS patients. In this cohort, CRS patients
      demonstrated deficits in retronasal olfaction, with worse scores in patients with
      nasal polyposis, asthma, and AERD. Retronasal olfaction scores correlate with
      degree of inflammation of the olfactory cleft. Retronasal olfaction correlated
      strongly with orthonasal olfaction and patient-reported smell and taste metrics,
      although orthonasal olfaction may have a stronger correlation with these metrics.
      LEVEL OF EVIDENCE: NA. Laryngoscope, 2437-2442, 2018.

PMID- 29637565
TI  - An Automated Two-dimensional Pairwise form Registration Method for Pair-matching
      of Fragmented Skeletal Remains.
AB  - This study introduces an automated pairwise method for osteological pair-matching
      of fragmented skeletal remains using two-dimensional fragmented outlines
      extracted from photographs. The form data are used in pairwise iterative closest
      point registrations with rigid transformations. A modified version of the average
      Hausdorff distance is calculated to remove any coordinate correspondences with
      outline fracture margins, which allow the distance analysis of fragmented
      outlines. A dilation modification to the Hausdorff distance is proposed creating
      a greater separation between true- and false-pairs. The sample consists of 122
      calcanei (61 pairs) from the UI-Stanford collection. Performance statistics are
      provided for simulated fragmented and complete assemblages. Results indicate up
      to 98% accuracy for fragmented and complete assemblages. The dilated Hausdorff
      distance performed similarly across assemblages, but showed a slight decrease in
      performance for the complete assemblage. This approach provides a useful short
      listing tool to reduce the number of visual comparisons required in large
      commingled assemblages.

PMID- 29637566
TI  - Redefining normal hemoglobin and anemia in singleton and twin pregnancies.
AB  - OBJECTIVE: To assess the benefit of a hemoglobin cutoff of 105 g/L as a trigger
      for anemia evaluation during the second trimester of pregnancy. METHODS: The
      present cross-sectional study, conducted at a health center in Israel between
      January 1, 2010, and December 31, 2015, included pregnant women with hemoglobin
      values below 105 g/L who were assessed for anemia. Anemia workup included
      complete blood count, serum ferritin and vitamin B12 measurements, and hemoglobin
      electrophoresis. The primary outcome was the incidence of nondilutional anemia,
      defined by a positive workup, across predefined hemoglobin thresholds. Receiver
      operating characteristic curves were created to identify the best hemoglobin
      threshold for predicting anemia, mandating further evaluation. RESULTS: In total,
      651 women with singleton and 300 women with twin pregnancies were evaluated for
      nondilutional anemia. Of these, 340 (52.2%) and 127 (42.3%) women, respectively,
      had positive workup results. The most common cause was iron deficiency. The
      hemoglobin values that best predicted positive workup results were 100 g/L in
      singleton pregnancies and 97 g/L in twin pregnancies. CONCLUSION: Anemia
      evaluation could be unnecessary in pregnant women with a hemoglobin value of 100
      105 g/L. Consideration should be given to redefining anemia in singleton and twin
      pregnancies.

PMID- 29637567
TI  - Narcissism and the pursuit of status.
AB  - OBJECTIVE: The purpose of the present studies was to examine the connections that
      narcissistic admiration and narcissistic rivalry had with various aspects of
      status. METHOD: Study 1 examined the associations that narcissism had with the
      motivation to seek status in a sample of 1,219 community members. Study 2
      examined whether narcissism interacted with the status-seeking motive to predict
      how individuals pursued status in a sample of 760 community members and college
      students. Study 3 used a daily diary approach to examine whether narcissism
      moderated the associations that daily perceptions of status and affiliation had
      with state self-esteem in 356 college students. RESULTS: Our results revealed
      that narcissistic admiration and narcissistic rivalry were somewhat similar in
      their desire for status but had divergent associations with other aspects of
      status (e.g., strategies employed to attain status, perceptions of status,
      reactions to perceived status). CONCLUSIONS: The results of the present studies
      suggest that narcissistic admiration is associated with an agentic orientation to
      the pursuit of status, whereas narcissistic rivalry is associated with an
      antagonistic orientation to the pursuit of status. Discussion focuses on the
      implications of these results for our understanding of the connections between
      narcissism and status.

PMID- 29637568
TI  - Hepatoma cell-secreted exosomal microRNA-103 increases vascular permeability and
      promotes metastasis by targeting junction proteins.
AB  - : Increased vascular permeability facilitates metastasis. Emerging evidence
      indicates that secreted microRNAs (miRNAs) may mediate the crosstalk between
      cancer and stromal cells. To date, whether and how secreted miRNAs affect
      vascular permeability remains unclear. Based on deep sequencing and quantitative
      PCR, we found that higher level of serum miR-103 was associated with higher
      metastasis potential of hepatocellular carcinoma (HCC). The in vitro endothelial
      permeability and transendothelial invasion assays revealed that the conditioned
      media or exosomes derived from high miR-103-expressing hepatoma cells increased
      the permeability of endothelial monolayers, but this effect was attenuated if
      exosome secretion of hepatoma cells was blocked by silencing ALIX and HRS or if
      miR-103 within hepatoma or endothelial cells was antagonized. Most importantly,
      pretreating endothelial monolayers with exosomes that were from stable miR-103
      expressing hepatoma cells facilitated the transendothelial invasion of tumor
      cells, and this role of exosomes was abrogated by inhibiting miR-103 in
      endothelial cells. Further in vivo analyses disclosed that mice with xenografts
      of stable miR-103-expressing hepatoma cells exhibited higher vascular
      permeability in tumor, higher level of exosomal miR-103 and greater number of
      tumor cells in blood circulation, and increased rates of hepatic and pulmonary
      metastases, compared to control mice. Mechanism investigations revealed that
      hepatoma cell-secreted miR-103 could be delivered into endothelial cells via
      exosomes, and then attenuated the endothelial junction integrity by directly
      inhibiting the expression of VE-Cadherin (VE-Cad), p120-catenin (p120) and zonula
      occludens 1. Moreover, miR-103 could also promote tumor cell migration by
      repressing p120 expression in hepatoma cells. CONCLUSION: Hepatoma cell-secreted
      exosomal miR-103 increases vascular permeability and promotes tumor metastasis by
      targeting multiple endothelial junction proteins, which highlights secreted miR
      103 as a potential therapeutic target and a predictive marker for HCC metastasis.
      (Hepatology 2018).

PMID- 29637569
TI  - Colour differences in Caucasian and Oriental women's faces illuminated by white
      light-emitting diode sources.
AB  - OBJECTIVE: To provide an approach to facial contrast, analysing CIELAB colour
      differences (DeltaEab,10*) and its components in women's faces from two different
      ethnic groups, illuminated by modern white light-emitting diodes (LEDs) or
      traditional illuminants recommended by the International Commission on
      Illumination (CIE). METHODS: We performed spectrophotometric measurements of
      spectral reflectance factors on forehead and cheek of 87 young healthy women (50
      Caucasians and 37 Orientals), plus five commercial red lipsticks. We considered a
      set of 10 white LED illuminants, representative of technologies currently
      available on the market, plus eight main illuminants currently recommended by the
      CIE, representative of conventional incandescent, daylight and fluorescent light
      sources. Under each of these 18 illuminants, we analysed the magnitude and
      components of DeltaEab,10* between Caucasian and Oriental women (considering
      cheek and forehead), as well as for cheek-forehead and cheek-lipsticks in
      Caucasian and Oriental women. Colour-inconstancy indices for cheek, forehead and
      lipsticks were computed, assuming D65 and A as reference illuminants. RESULTS:
      DeltaEab,10* between forehead and cheek were quantitatively and qualitatively
      different in Orientals and Caucasians, but discrepancies with respect to average
      values for 18 illuminants were small (1.5% and 5.0% for Orientals and Caucasians,
      respectively). DeltaEab,10* between Caucasians and Orientals were also
      quantitatively and qualitatively different both for forehead and cheek, and
      discrepancies with respect to average values were again small (1.0% and 3.9% for
      forehead and cheek, respectively). DeltaEab,10* between lipsticks and cheek were
      at least two times higher than those between forehead and cheek. Regarding
      DeltaEab,10* between lipsticks and cheeks, discrepancies with respect to average
      values were in the range 1.5-12.3%, although higher values of up to 54.2% were
      found for a white RGB LED. This white RGB LED provided the highest average colour
      inconstancy indices: 17.1 and 11.5 CIELAB units, under reference illuminants D65
      and A, respectively. CONCLUSION: Colour contrasts in women's faces under CIE
      standard illuminants for outdoor and indoor conditions may be strongly altered
      using specific white LEDs. More research needs to be performed on the impact of
      spectral power distribution of light sources with high colour rendering indices
      on visual colour appearance of cosmetic products.

PMID- 29637570
TI  - Determination of four antiepileptic drugs in plasma using ultra-performance
      liquid chromatography with mass detection technique.
AB  - Status epilepticus (SE) is considered the second most frequent neurological
      emergency. Its therapeutic management is performed using sequential antiepileptic
      drug regimens. Diazepam (DIA), midazolam (MID), phenytoin (PHT) and phenobarbital
      (PB) are four drugs of different classes used sequentially in the management of
      SE. A sensitive, selective, accurate and precise method was developed and
      validated for simultaneous determination of the four antiepileptic drugs in human
      plasma. Their separation and quantification were achieved using ultra-performance
      liquid chromatography (UPLC) with mass detection using carbamazepine as internal
      standard (IS). For the first three drugs and the IS, UPLC-MS/MS with electrospray
      ionization working in multiple reaction monitoring mode was used at the following
      transitions: m/z 285 -> 193 for DIA; m/z 326 -> 291 for MID; m/z 253 -> 182 for
      PHT; and m/z 237 -> 194, 237 -> 192 for IS. For the fourth drug (PB), a molecular
      ion peak of PB [M + H] + at m/z 233 was used for its quantitation. The method was
      linear over concentration ranges 5-500 ng/mL for DIA and MID and 0.25-20 MUg/mL
      for PHT and PB. Bioanalytical validation of the developed method was carried out
      according to European Medicines Agency guidelines. The developed method can be
      applied for routine drug analysis, therapeutic drug monitoring and bioequivalence
      studies.

PMID- 29637571
TI  - Long-term outcomes in oral cavity squamous cell carcinoma with adjuvant and
      salvage radiotherapy after surgery.
AB  - OBJECTIVE: Early-stage oral cavity squamous cell carcinoma (OCSCC) represents a
      heterogeneous group of patients, and locoregional recurrence rates are as high as
      25% with surgery alone. Radiotherapy (RT) is typically reserved as part of
      salvage multimodality therapy after salvage surgery because it is generally
      thought that there is no significant detriment to salvage therapy. Our aim was to
      examine outcomes for recurrent OCSCC treated with salvage surgery and radiation
      and compare them to outcomes for patients treated with adjuvant postoperative RT
      upfront. METHODS: We identified 425 patients with OCSCC treated with
      postoperative RT at our institution. The 5-year rates of local failure,
      locoregional failure (LRF), survival, and distant metastasis (DM) were the main
      outcome measures. We performed a landmark analysis and examined the same outcomes
      in the adjuvant versus salvage cohorts using Cox proportional hazards and Fine
      Gray competing risk method. RESULTS: The adjuvant cohort had higher tumor (T) (P
      < 0.0001) and nodal (N) (P < 0.0001) stage than the salvage cohort's stage at
      initial presentation. On multivariate analysis, a strategy of salvage RT
      experienced poorer overall survival (OS) compared to upfront adjuvant RT (hazard
      ratio [HR] 1.84; 95% confidence interval [CI], 1.26-2.70; P = 0.002). Moreover,
      salvage surgery followed by RT patients experienced increasing risk of LRF (HR
      1.56; 95% CI, 1.18-2.06; P = 0.002) and (DM) (HR 1.53; 95% CI, 1.08-2.17; P =
      0.02) on multivariate analysis. Additional analysis was performed excluding
      salvage cohort with advanced disease at initial presentation (T3-T4 and N2).
      Salvage RT treatment selection for early-stage OCSCC continued to experience
      significantly poorer OS as compared to adjuvant RT (HR 1.48; 95% CI, 1.002-2.19;
      P = 0.049). CONCLUSION: Early-stage OCSCC patients who are observed and
      experienced recurrence requiring salvage therapy (surgery and RT) have worse
      oncologic outcomes than locally advanced patients receiving upfront adjuvant RT.
      Prospective randomized studies are needed to identify high-risk subset of early
      stage OCSCC comparing adjuvant RT versus observation, followed by salvage surgery
      and RT at recurrence. LEVEL OF EVIDENCE: 4. Laryngoscope, 2539-2545, 2018.

PMID- 29637572
TI  - Hepatic CREBZF couples insulin to lipogenesis by inhibiting insig activity and
      contributes to hepatic steatosis in diet-induced insulin-resistant mice.
AB  - : Insulin is critical for the regulation of de novo fatty acid synthesis, which
      converts glucose to lipid in the liver. However, how insulin signals are
      transduced into the cell and then regulate lipogenesis remains to be fully
      understood. Here, we identified CREB/ATF bZIP transcription factor (CREBZF) of
      the activating transcription factor/cAMP response element-binding protein
      (ATF/CREB) gene family as a key regulator for lipogenesis through insulin-Akt
      signaling. Insulin-induced gene 2a (Insig-2a) decreases during refeeding,
      allowing sterol regulatory element binding protein 1c to be processed to promote
      lipogenesis; but the mechanism of reduction is unknown. We show that Insig-2a
      inhibition is mediated by insulin-induced CREBZF. CREBZF directly inhibits
      transcription of Insig-2a through association with activating transcription
      factor 4. Liver-specific knockout of CREBZF causes an induction of Insig-2a and
      Insig-1 and resulted in repressed lipogenic program in the liver of mice during
      refeeding or upon treatment with streptozotocin and insulin. Moreover, hepatic
      CREBZF deficiency attenuates hepatic steatosis in high-fat, high-sucrose diet-fed
      mice. Importantly, expression levels of CREBZF are increased in livers of diet
      induced insulin resistance or genetically obese ob/ob mice and humans with
      hepatic steatosis, which may underscore the potential role of CREBZF in the
      development of sustained lipogenesis in the liver under selective insulin
      resistance conditions. CONCLUSION: These findings uncover an unexpected mechanism
      that couples changes in extracellular hormonal signals to hepatic lipid
      homeostasis; disrupting CREBZF function may have the therapeutic potential for
      treating fatty liver disease and insulin resistance. (Hepatology 2018).

PMID- 29637573
TI  - Ultrasound Appearances of Pediatric Testicular Yolk Sac Tumors: Twenty-one Cases
      in a Single Institution.
AB  - Testicular yolk sac tumors are rare, and analyses of relevant ultrasound (US)
      findings are limited. We retrospectively reviewed the US features of 21
      pathologically verified cases (patients aged 10-64 months). Neoplasms were
      unilateral and solitary, occupying part (focal) or all (diffuse) of the testis.
      Focal lesions (14 cases) were usually solid and ovoid, with a homogeneous echo
      texture or multiple random anechoic spaces, and hypervascular. Diffuse neoplasms
      had heterogeneous echo textures; most were hypervascular. On spectral Doppler US
      imaging, 11 cases had a mean peak systolic velocity of 12.9 cm/s and a mean
      resistive index of 0.54. Ultrasound is a useful tool for imaging pediatric testes
      when a yolk sac tumor is suspected.

PMID- 29637574
TI  - Outcome parameters associated with perceived helpfulness of family-based
      treatment for adolescent eating disorders.
AB  - OBJECTIVE: Family-based treatment (FBT) is an efficacious treatment for
      adolescent eating disorders, yet it is not routinely implemented in clinical
      practice. Given that consumers play a role in treatment selection, this study
      sought to examine families' perspectives on FBT and remission markers associated
      with increased treatment satisfaction across families. METHOD: Participants were
      40 adolescents and 43 caregivers who received outpatient FBT. FBT helpfulness was
      assessed using a treatment follow-up questionnaire, and eating disorder
      symptomatology was assessed using percent expected body weight (%EBW) and the
      eating disorder examination (EDE). Regression analyses were used to assess
      whether changes in symptoms from baseline to end-of-treatment (EOT) were
      significantly associated with helpfulness reports. RESULTS: On average, patients
      and their parents perceived FBT as "quite helpful" and "extremely helpful,"
      respectively. Improvements in all EDE subscales, with the exception of restraint,
      were significantly associated with adolescent report of helpfulness (all p <
      .05); increase in %EBW was significantly associated with maternal report of
      helpfulness (p = .03). There were no significant findings for paternal report.
      DISCUSSION: Both patients and their parents perceived FBT as helpful, but
      patients seemed to prioritize cognitive improvements while mothers prioritized
      physical improvements in rating their satisfaction with FBT.

PMID- 29637575
TI  - The RNA-Seq-based high resolution gene expression atlas of chickpea (Cicer
      arietinum L.) reveals dynamic spatio-temporal changes associated with growth and
      development.
AB  - Chickpea is one of the world's largest cultivated food legumes and is an
      excellent source of high-quality protein to the human diet. Plant growth and
      development are controlled by programmed expression of a suite of genes at the
      given time, stage, and tissue. Understanding how the underlying genome sequence
      translates into specific plant phenotypes at key developmental stages,
      information on gene expression patterns is crucial. Here, we present a
      comprehensive Cicer arietinum Gene Expression Atlas (CaGEA) across different
      plant developmental stages and organs covering the entire life cycle of chickpea.
      One of the widely used drought tolerant cultivars, ICC 4958 has been used to
      generate RNA-Seq data from 27 samples at 5 major developmental stages of the
      plant. A total of 816 million raw reads were generated and of these, 794 million
      filtered reads after quality control (QC) were subjected to downstream analysis.
      A total of 15,947 unique number of differentially expressed genes across
      different pairwise tissue combinations were identified. Significant differences
      in gene expression patterns contributing in the process of flowering, nodulation,
      and seed and root development were inferred in this study. Furthermore,
      differentially expressed candidate genes from "QTL-hotspot" region associated
      with drought stress response in chickpea were validated.

PMID- 29637576
TI  - The Effect of Geographic Proximity to Unconventional Oil and Gas Development on
      Public Support for Hydraulic Fracturing.
AB  - With the rapid growth of unconventional oil and natural gas development
      transforming the U.S. economic and physical landscape, social scientists have
      increasingly explored the spatial dynamics of public support for this issue-that
      is, whether people closer to unconventional oil and gas development are more
      supportive or more opposed. While theoretical frameworks like construal-level
      theory and the "Not in My Backyard" (or NIMBY) moniker provide insight into these
      spatial dynamics, case studies in specific locations experiencing energy
      development reveal substantial variation in community responses. Larger-scale
      studies exploring the link between proximity and support have been hampered by
      data quality and availability. We draw on a unique data set that includes geo
      coded data from national surveys (nine waves; n = 19,098) and high-resolution
      well location data to explore the relationship between proximity and both
      familiarity with and support for hydraulic fracturing. We use two different
      measures of proximity-respondent distance to the nearest well and the density of
      wells within a certain radius of the respondent's location. We find that both
      types of proximity to new development are linked to more familiarity with
      hydraulic fracturing, even after controlling for various individual and
      contextual factors, but only distance-based proximity is linked to more support
      for the practice. When significant, these relationships are similar to or exceed
      the effects of race, income, gender, and age. We discuss the implications of
      these findings for effective risk communication as well as the importance of
      incorporating spatial analysis into public opinion research on perceptions of
      energy development.

PMID- 29637577
TI  - Are age and gender suitable matching criteria in organ dose reconstruction using
      surrogate childhood cancer patients' CT scans?
AB  - PURPOSE: The purpose of this work was to assess the feasibility of using
      surrogate CT scans of matched patients for organ dose reconstructions for
      childhood cancer (CC) survivors, treated in the past with only 2D imaging data
      available instead of 3D CT data, and in particular using the current literature
      standard of matching patients based on similarity in age and gender. METHODS:
      Thirty-one recently treated CC patients with abdominal CT scans were divided into
      six age- and gender-matched groups. From each group, two radiotherapy plans for
      Wilms' tumor were selected as reference plans and applied to the age- and gender
      matched patients' CTs in the respective group. Two reconstruction strategies were
      investigated: S1) without field adjustments; S2) with manual field adjustments
      according to anatomical information, using a visual check in digitally
      reconstructed radiographs. To assess the level of agreement between the
      reconstructed and the reference dose distributions, we computed (using a
      collapsed cone algorithm) and compared the absolute deviation in mean and maximum
      dose normalized by the prescribed dose (i.e., normalized errors |NEmean | and
      |NE2cc |) in eight organs at risk (OARs): heart, lungs, liver, spleen, kidneys,
      and spinal cord. Furthermore, we assessed the quality of a reconstruction case by
      varying acceptance thresholds for |NEmean | and |NE2cc |. A reconstruction case
      was accepted (i.e., considered to pass) if the errors in all OARs are smaller
      than the threshold. The pass fraction for a given threshold was then defined as
      the percentage of reconstruction cases that were classified as a pass.
      Furthermore, we consider the impact of allowing to use a different CT scan for
      each OAR. RESULTS: Slightly smaller reconstruction errors were achieved with S2
      in multiple OARs than with S1 (P < 0.05). Among OARs, the best reconstruction was
      found for the spinal cord (average |NEmean | and |NE2cc | <= 4%). The largest
      average |NEmean | was found in the spleen (18%). The largest average |NE2cc | was
      found in the left lung (26%). Less than 30% of the reconstruction cases (i.e.,
      pass fraction) meet the criteria that |NEmean | < 20% and |NE2cc | < 20% in all
      OARs when using age and gender matching and a single CT to do reconstructions.
      Allowing other matchings and combining reconstructions for OARs from multiple
      patients, the pass fraction increases substantially to more than 60%.
      CONCLUSIONS: To conclude, reconstructions with small deviations can be obtained
      by using CC patients' CT scans, making the general approach promising. However,
      using age and gender as the only matching criteria to select a CT scan for the
      reconstruction is not sufficient to guarantee sufficiently low reconstruction
      errors. It is therefore suggested to include more features (e.g., height,
      features extracted from 2D radiographs) than only age and gender for dose
      reconstruction for CC survivors treated in the pre-3D radiotherapy planning era
      and to consider ways to combine multiple reconstructions focused on different
      OARs.

PMID- 29637578
TI  - Role Of spinal mechanisms in the pathophysiology of the split hand sign in
      amyotrophic lateral sclerosis.

PMID- 29637579
TI  - Defect propagation in NiTi rotary instruments: a noncontact optical profilometry
      analysis.
AB  - AIM: To evaluate the presence and propagation of defects and their effects on
      surfaces of nickel-titanium (NiTi) instruments using noncontact, three
      dimensional optical profilometry, and to assess the accuracy of this method of
      investigation. METHODOLOGY: The flute surface areas of instruments from two
      commercial instrumentation systems, namely Reciproc R25 (n = 5) and WaveOne
      Primary (n = 5), were assessed and compared before and after performing two
      instrumentation cycles in simulated root canals in clear resin blocks. All the
      analyses were conducted on areas measuring 211 * 211 MUm, located 3 mm from the
      tips of the instruments. A quantitative analysis was conducted before and after
      the first and second instrumentation cycles, using the Sa (average roughness over
      the measurement field), Sq (root mean square roughness) and Sz (average height
      over the measurement field) amplitude parameters. All the data were submitted to
      statistical analysis at a 5% level of significance. RESULTS: There was a
      significant increase (P = 0.007) in wear in both groups, especially between
      baseline and the second instrumentation cycle, with significantly higher wear
      values being observed on WaveOne instruments (Sz median values = 33.68 and 2.89
      MUm, respectively, for WO and RP groups). A significant increase in surface
      roughness (P = 0.016 and P = 0.008, respectively, for Sa and Sq) was observed in
      both groups from the first to the second instrumentation cycle, mostly in WaveOne
      specimens. Qualitative analysis revealed a greater number of defects on the flute
      topography of all the instruments after use. CONCLUSIONS: More defects were
      identified in WaveOne Primary instruments compared to Reciproc R25, irrespective
      of the evaluation stage. The investigation method provided an accurate,
      repeatable and reproducible assessment of NiTi instruments at different time
      points.

PMID- 29637580
TI  - The clinical utility of pharmacometric models.

PMID- 29637581
TI  - Influence of Progenitor-Derived Regeneration Markers on Hepatitis C Virus-Related
      Cirrhosis Outcome (ANRS CO12 CirVir Cohort).
AB  - : Progenitor-derived regeneration gives rise to the aberrant expression of
      biliary markers such as cytokeratin 7 (K7) and epithelial cell adhesion molecule
      (EpCAM) in hepatocytes. We aimed to describe the expression of these molecules in
      patients with compensated hepatitis C virus (HCV)-related cirrhosis and to
      investigate its potential influence on cirrhosis complications. Among patients
      with Child-Pugh A uncomplicated HCV-related cirrhosis enrolled in the prospective
      ANRS CO12 CirVir cohort, we selected individuals with a liver biopsy collected
      within 2 years before inclusion in the study. K7 and EpCAM immunostaining
      identified intermediate hepatobiliary cells. The influence of biliary marker
      expres-sion in hepatocytes on decompensation events and the occurrence of
      hepatocellular carcinoma (HCC) was studied using a multivariate Cox proportional
      hazards regression model. Among the 337 patients eligible for the study (men,
      67%; median age, 52 years), 198 (58.8%) had biopsies with K7-positive hepatocytes
      including extensive staining in 40 (11.9%) and 203 had EpCAM-positive hepatocytes
      (60.6%). During follow-up (median, 54.2 months), 47 patients (14%) experienced a
      decompensation event, and HCC was diagnosed in 37 patients (11%). Extensive K7
      staining was independently associated with the occurrence of a decompensation
      event (hazard ratio [HR], 3.00; 95% confidence interval [CI], 1.30-6.89; P =
      0.010). EpCAM expression was independently associated with HCC occurrence (HR,
      2.37; 95% CI, 1.07-5.23; P =0.033) along with age and a low prothrombin ratio.
      CONCLUSION: Progenitor-derived regeneration depicted by K7 and EpCAM
      immunostaining of hepatocytes in liver biopsies of patients with compensated HCV
      related cirrhosis marks a cirrhosis stage more prone to develop complications.
      (HEPATOLOGY 2018; 68:1534-1548).

PMID- 29637582
TI  - Clinical bleeding and thrombin generation in admissions to critical care with
      prolonged prothrombin time: an exploratory study.
AB  - BACKGROUND: Prolongation of prothrombin time (PT) is often recorded in critical
      illness, but has limited ability to predict risk of bleeding. This exploratory
      study was aimed at assessing a role for thrombin generation (TG) to predict
      bleeding. STUDY DESIGN AND METHODS: TG was measured by calibrated automated
      thrombography in admissions to intensive care with prolonged PT. Bleeding events
      were recorded up to Day 5 after enrollment and correlated with results of PT
      ratio (PTR) and variables of TG. RESULTS: A total of 306 patients were recruited.
      A total of 101 bleeding events developed in 46 patients during the period of
      observation. Many patients with prolonged PT had endogenous thrombin potential
      (ETP), which was within the normal range (120/251 patients, 47.8%) or even
      elevated (8%). Although some patients had a reduction in ETP or peak thrombin,
      these were present over a wide range of PTR. There was no suggestion by receiver
      operating characteristic analysis that variables of conventional TG were
      sensitive at predicting bleeding. No bleeding events were documented in patients
      defined as ETP high, despite elevated PTR. CONCLUSION: Future studies need to
      explore a role for alternatives tests of coagulation in critical illness.
      Development of TG assays is required to positively identify more patients at
      increased bleeding risk or to exclude a larger number at low risk and how this
      relates to subgroups, such as patients with liver disease, and the need for
      prophylactic plasma transfusion.

PMID- 29637583
TI  - Parental psychosocial factors and childhood caries prevention: Data from an
      American Indian population.
AB  - OBJECTIVES: The objective of this study was to examine the association among
      psychological and social variables reported by American Indian parents/caregivers
      of preschool children and changes in their Oral Health Knowledge and Behaviors
      related to care of their children's teeth. We also investigated the relationship
      of these factors with progression of caries, as reflected by changes in their
      children's dmfs. METHODS: The data used for this study were collected at baseline
      in a clinical trial of an oral health promotion intervention comprising
      behavioural and clinical interventions for caries prevention delivered by tribal
      members on a large Southwestern American Indian reservation. Linear regression
      analyses were performed for changes (baseline to Year 1) in dmfs, Oral Health
      Knowledge and Oral Health Behavior scores, with baseline psychosocial measures,
      taken individually, as the independent variables. RESULTS: Parents' attitudes and
      beliefs were associated with increases in their Oral Health Knowledge and
      Behavior and also with the progression of caries for their children. When all
      participants were considered together, increases in children's dmfs were smaller
      when the caregiver had higher Internal Oral Health Locus of Control (e = -1.33, P
      = .004), higher Health Literacy (e = -1.55, P < .01), and higher Financial
      Stability (e = -4.46, P = .03), and lower scores for the Barriers subscale (e =
      1.57, P < .01) of the Health Belief Model. For parents in the Intervention group,
      higher scores on Locus of Control, reflecting beliefs that chance, or other
      people determine their children's oral health, were associated with larger
      increases in Oral Health Knowledge (e = 1.73, P = .04) and Behaviors (e = 4.00, P
      = .005). CONCLUSIONS: Prevention of early childhood caries in American Indian
      children has proved to be especially challenging. Some of the measures identified
      in this report may suggest promising directions to prevention through approaches
      that build on competencies and skills to be learned and used within a context
      more broadly focused on parenting and management of health and family challenges.

PMID- 29637584
TI  - The glucagon-like peptide-1 receptor agonist Exendin-4, ameliorates contrast
      induced nephropathy through suppression of oxidative stress, vascular dysfunction
      and apoptosis independent of glycaemia.
AB  - Contrast-induced nephropathy (CIN) is a leading cause of hospital-acquired acute
      kidney injury, particularly in diabetic patients. Previous studies have shown
      renoprotective effects of glucagon-like peptide-1 (GLP-1) signalling; however,
      its role in CIN remains unexplored. This study investigates the prophylactic
      effect of exendin-4, a GLP-1R agonist, against CIN in a rat model mimicking both
      healthy and diabetic conditions. Animals were randomly divided into 7 groups: a
      control sham group (n = 8), and 2 identical sets of 3 disease groups, one
      received exendin-4 before exposure to contrast medium (CM), while the other
      served as untreated control. The 3 disease groups represented diabetes (n = 8),
      CIN (n = 8), or diabetes and CIN combined (n = 8). Untreated groups showed
      deteriorating renal function as indicated by significantly higher levels of serum
      creatinine and blood urea nitrogen, malondialdehyde, and endothelin-1 and caspase
      3 expression compared to the sham control group. This was accompanied by a
      significant decrease in tissue reserves of reduced glutathione, superoxide
      dismutase, nitrate and endothelin nitric oxide synthase as well as deteriorating
      renal histology. The CM-induced changes in diabetic rats indicate impaired renal
      function, oxidative stress, vascular dysfunction, and apoptosis, and were
      significance higher in intensity compared to non-diabetic rats. Pretreatment with
      exendin-4 ameliorated all the aforementioned CM-induced nephropathic effects
      independent of the glycemic state. To our knowledge, this is the first study
      describing the prophylactic renoprotective effects of exendin-4 against CIN. With
      the current pharmaceutical use of exendin-4 as a hypoglycaemic agent, the GLP-1R
      agonist becomes an interesting candidate for human clinical trials on CIN
      prevention.

PMID- 29637585
TI  - Impact of HBV genotype and mutations on HBV DNA and qHBsAg levels in patients
      with HBeAg-negative chronic HBV infection.
AB  - BACKGROUND: HBV DNA and quantitative (q)HBsAg levels as prognostic markers for
      HBV-related disease are mostly validated in Asia and their significance in
      Western populations is uncertain. AIM: To analyse the impact of the HBV genotype
      and frequent mutations in precore (PC), basal core promoter (BCP) and preS on HBV
      DNA and qHBsAg levels. METHODS: HBV DNA and qHBsAg serum levels of 465 patients
      with HBeAg-negative chronic HBV infection were correlated with the HBV genotype
      and mutations in PC, BCP and preS. For a detailed analysis of the molecular
      virology, genotype A2 genomes harbouring these mutations were analysed for
      replication efficacy and HBsAg release in cell culture. RESULTS: While no impact
      of the HBV genotype on HBV DNA levels was observed, qHBsAg levels differed up to
      1.4 log among the genotypes (P < 0.001), reflected by large differences regarding
      the 1000 IU/mL HBsAg cut-off. While PC mutations were associated with higher (P <
      0.001), BCP mutations were associated with lower HBV DNA levels (P < 0.001).
      Higher qHBsAg levels were associated with preS and lower levels with PC mutations
      (P < 0.001 and P = 0.001, respectively). The cell culture experiments revealed a
      higher HBsAg release and shorter filaments in case of a HBV genome harbouring a
      preS deletion. In contrast, a perinuclear HBsAg accumulation was detected for the
      PC and BCP-variants, reflecting an impaired HBsAg release. CONCLUSIONS: qHBsAg
      serum levels depend on the HBV genotype and together with HBV DNA levels on
      frequent mutations in PC, BCP and preS in HBeAg-negative patients. qHBsAg cut
      offs when used as prognostic markers require genotype-dependent validation.

PMID- 29637586
TI  - Influence Factors on Contrast Agent Venous Intravasation During Transvaginal 4
      Dimensional Hysterosalpingo-Contrast Sonography.
AB  - OBJECTIVES: To explore the risk factors on contrast agent venous intravasation
      during transvaginal 4-dimensional hysterosalpingo-contrast sonography (TVS 4D
      HyCoSy). METHODS: The TVS 4D-HyCoSy imaging data were collected from 276 female
      infertile patients. The correlation between endometrial thickness, days after
      menstruation, intrauterine intervention history, fallopian tubal patency degree,
      and contrast agent venous intravasation, respectively, was analyzed. RESULTS: In
      our study, the incidence of contrast agent venous intravasation was 13.04%.
      Endometrial thickness and days after menstruation were significantly associated
      with venous intravasation (P < .05). However, there was no significance for
      intrauterine intervention history and fallopian tube patency degree. CONCLUSIONS:
      Contrast agent intravasation during TVS 4D-HyCoSy is not infrequent. Performing
      TVS 4D-HyCoSy according to endometrial thickness and menstrual period could
      reduce intravasation incidence to some extent.

PMID- 29637587
TI  - PD-L1 expression in tumour-infiltrating lymphocytes is a poor prognostic factor
      for primary acral melanoma patients.
AB  - AIMS: Programmed cell death protein 1-programmed death-ligand 1 (PD-L1) blockade
      immunotherapy has shown notable therapeutic benefit in metastatic melanoma, but
      the clinical relevance of PD-L1 expression remains unclear in melanoma,
      especially in acral melanoma, which is the most common subtype in Asians. The aim
      of this study was to evaluate the clinical effect of PD-L1 expression in primary
      acral melanoma. METHODS AND RESULTS: We used immunohistochemistry to evaluate PD
      L1 expression in tumour cells and tumour-infiltrating lymphocytes (TILs), and
      analysed its associations with clinicopathological features and survival in 78
      primary acral melanoma patients. We found that expression of PD-L1 in tumour
      cells and TILs occurred exclusively in a tumour-stroma interface pattern,
      consistent with the predominant pattern of TIL distribution. The presence of
      peritumoral TILs was also associated with high PD-L1 expression in tumour cells.
      Furthermore, PD-L1 expression in tumour cells and that in TILs showed a close
      relationship (Spearman's rho = 0.381, P = 0.001). However, neither PD-L1
      expression in tumour cells nor that in TILs was significantly correlated with
      clinicopathological features. In univariate analysis, cases with PD-L1-positive
      TILs had significantly poorer survival than those with PD-L1-negative TILs
      (median disease-specific survival of 40.7 months versus 78.0 months; P = 0.008).
      In multivariate analysis, PD-L1 expression in TILs was an independent factor for
      poor prognosis (P = 0.032), whereas PD-L1 expression in tumour cells was not
      significantly correlated with survival in univariate analysis (P = 0.378) and
      multivariate analysis (P = 0.354). CONCLUSION: This is the first study to
      demonstrate that PD-L1 expression in TILs, but not that in tumour cells, is an
      independent predictor of poor prognosis in acral melanoma.

PMID- 29637589
TI  - Multiplatform Genomic Roadmap of Hepatocellular Carcinoma: A Matter of Molecular
      Heterogeneity.

PMID- 29637588
TI  - Population pharmacokinetics of tacrolimus in children with nephrotic syndrome.
AB  - AIMS: Nephrotic syndrome (NS) is the most common clinical manifestation of
      glomerular disease in children. Currently, tacrolimus (TAC) is widely used in
      children with NS. However, pharmacokinetic data in children with nephrotic
      syndrome is limited. This study was intended to evaluate the population
      pharmacokinetics (PPK) of TAC in paediatric NS and to optimize dosing regimen.
      METHODS: Blood samples from NS children treated with TAC were collected and the
      blood concentrations of TAC were detected using HPLC-MS/MS. A PPK model was
      developed using NONMEM software. Pharmacogenetic analysis was carried out in the
      CYP3A5 gene. RESULTS: The data from 28 children were used for PPK analysis. A one
      compartment model and first-order elimination were accorded with the TAC data in
      paediatric NS. A covariate analysis showed that body weight and CYP3A5 genotype
      significantly affected TAC pharmacokinetics. Monte Carlo simulation indicated
      that NS children with CYP3A5*3/*3 receiving 0.10 mg kg-1  dose-1 twice daily and
      NS children with CYP3A5*1 receiving 0.25 mg kg-1  dose-1 twice daily TAC could
      achieve the target concentrations of 5-10 ng ml-1 . CONCLUSION: The PPK of TAC
      was estimated in children with NS and a CYP3A5 genotype-based dosing regimen was
      set up based on simulations.

PMID- 29637590
TI  - Cannabis for Chronic Pain: Challenges and Considerations.
AB  - The National Academies of Sciences, Engineering, and Medicine has found
      substantial evidence that cannabis (plant) is effective for the treatment of
      chronic pain in adults, and moderate evidence that oromucosal cannabinoids
      (extracts, especially nabiximols) improve short-term sleep disturbances in
      chronic pain. The paradoxical superiority of the cannabis plant over cannabinoid
      molecules represents a challenge for the medical community and the established
      processes that define modern pharmacy. The expanding and variable legalization of
      cannabis in multiple states nationwide represents an additional challenge for
      patients and the medical community because recreational and medicinal cannabis
      are irresponsibly overlapped. Cannabis designed for recreational use (containing
      high levels of active ingredients) is increasingly available to patients with
      chronic pain who do not find relief with current pharmacologic entities, which
      exposes patients to potential harm. This article analyzes the available
      scientific evidence to address controversial questions that the current state of
      cannabis poses for health care professionals and chronic pain patients and sets
      the basis for a more open discussion about the role of cannabis in modern
      medicine for pain management. A critical discussion on these points, the legal
      status of cannabis, and considerations for health care providers is presented.

PMID- 29637591
TI  - Threshold Evaluation of Emergency Risk Communication for Health Risks Related to
      Hazardous Ambient Temperature.
AB  - Emergency risk communication (ERC) programs that activate when the ambient
      temperature is expected to cross certain extreme thresholds are widely used to
      manage relevant public health risks. In practice, however, the effectiveness of
      these thresholds has rarely been examined. The goal of this study is to test if
      the activation criteria based on extreme temperature thresholds, both cold and
      heat, capture elevated health risks for all-cause and cause-specific mortality
      and morbidity in the Minneapolis-St. Paul Metropolitan Area. A distributed lag
      nonlinear model (DLNM) combined with a quasi-Poisson generalized linear model is
      used to derive the exposure-response functions between daily maximum heat index
      and mortality (1998-2014) and morbidity (emergency department visits; 2007-2014).
      Specific causes considered include cardiovascular, respiratory, renal diseases,
      and diabetes. Six extreme temperature thresholds, corresponding to 1st-3rd and
      97th-99th percentiles of local exposure history, are examined. All six extreme
      temperature thresholds capture significantly increased relative risks for all
      cause mortality and morbidity. However, the cause-specific analyses reveal
      heterogeneity. Extreme cold thresholds capture increased mortality and morbidity
      risks for cardiovascular and respiratory diseases and extreme heat thresholds for
      renal disease. Percentile-based extreme temperature thresholds are appropriate
      for initiating ERC targeting the general population. Tailoring ERC by specific
      causes may protect some but not all individuals with health conditions
      exacerbated by hazardous ambient temperature exposure.

PMID- 29637592
TI  - Early weight loss predicts weight loss treatment response regardless of binge
      eating disorder status and pretreatment weight change.
AB  - OBJECTIVE: Individuals seeking weight loss treatment have diverse pretreatment
      weight trajectories, and once enrolled, individuals' response to weight loss
      treatments also varies greatly and may be influenced by the presence of binge
      eating disorder (BED). Reported average weight losses may obscure these
      considerable differences. This study examined whether BED status and different
      weight-related change variables are associated with successful weight loss
      treatment outcomes in a controlled treatment study. METHOD: Participants (N = 89)
      with overweight/obesity, with and without BED, participated in a 3-month weight
      loss trial in primary care with 3- and 12-month follow-ups. We tested the
      prognostic significance of four weight-related change variables (the last supper,
      early weight loss, pretreatment weight trajectory, weight suppression) on
      outcomes (weight loss-overall, weight loss-"subsequent," weight loss during
      second half of treatment). RESULTS: Early weight loss was positively associated
      with weight loss-overall at post-treatment, and at 3-month and 12-month follow
      up. Early weight loss was positively associated with weight loss-subsequent at
      post-treatment only. No other weight-related variables were significantly
      associated with weight loss. Models including BED status and treatment condition
      were not significant. DISCUSSION: Participants with early weight loss were more
      likely to continue losing weight, regardless of BED status or treatment
      condition. The results highlight the importance of early dedication to weight
      loss treatment to increase the likelihood of positive outcomes.

PMID- 29637594
TI  - Reply to "epidemiology of autoimmune versus infectious encephalitis".

PMID- 29637595
TI  - Making a master filterer: Ontogeny of specialized filtering plates in silver carp
      (Hypophthalmichthys molitrix).
AB  - Filter feeding fishes possess several morphological adaptations necessary to
      capture and concentrate small particulate matter from the water column. Filter
      feeding teleosts typically employ elongated and tightly packed gill rakers with
      secondary bony or epithelial modifications that increase filtering efficiency.
      The gill rakers of Hypophthalmichthys molitrix, silver carp, are anatomically
      distinct from and more complex than the filtering apparatus of other teleostean
      fishes. The silver carp filtering apparatus is composed of biserial, fused
      filtering plates used to capture particles ranging in size from 4 to 80 MUm.
      Early in ontogeny, at 15-25 mm standard length (SL), silver carp gill rakers are
      reminiscent of other more stereotypical teleostean rakers, characterized by
      individual lanceolate rakers that are tightly packed along the entirety of the
      branchial arches. At 30 mm SL, secondary epithelial projections and concomitant
      dermal ossification begin to stitch together individual gill rakers. During later
      juvenile stages, dermal bone further modifies the individual gill rakers and
      creates a bony scaffold that supports the now fully fused and porous epithelium.
      By adulthood, the stitching of bone and complete fusion of the overlying
      epithelium creates rigid filtering plates with morphologically distinct faces.
      The inner face of the plates is organized into a net-like matrix while the outer
      face has a sponge-like appearance comprised of differently sized pores. Here, we
      present morphological data from an ontogenetic series of the filtering apparatus
      within silver carp. These data inform hypotheses regarding both how these gill
      raker plates may have evolved from a more basal condition, as well as how this
      novel architecture allows this species to feed on exceedingly small
      phytoplankton, particles that represent a greater filtering challenge to the
      typical anatomy of the gill rakers of fishes.

PMID- 29637593
TI  - Pharmacological treatments for alleviating agitation in dementia: a systematic
      review and network meta-analysis.
AB  - AIMS: To determine the most efficacious and acceptable treatments of agitation in
      dementia. METHODS: MEDLINE, EMBASE, PsycINFO, CENTRAL and clinicaltrials.gov were
      searched up to 7 February 2017. Two independent reviewers selected randomized
      controlled trials (RCTs) of treatments to alleviate agitation in people with all
      types dementia. Data were extracted using standardized forms and study quality
      was assessed using the revised Cochrane Risk of Bias Tool for RCTs. Data were
      pooled using meta-analysis. The primary outcome, efficacy, was 8-week response
      rates defined as a 50% reduction in baseline agitation score. The secondary
      outcome was treatment acceptability defined as treatment continuation for 8
      weeks. RESULTS: Thirty-six RCTs comprising 5585 participants (30.9% male; mean +/
      standard deviation age, 81.8 +/- 4.9 years) were included.
      Dextromethorphan/quinidine [odds ratio (OR) 3.04; 95% confidence interval (CI),
      1.63-5.66], risperidone (OR 1.96; 95% CI, 1.49-2.59) and selective serotonin
      reuptake inhibitors as a class (OR 1.61; 95% CI, 1.02-2.53) were found to be
      significantly more efficacious than placebo. Haloperidol appeared less
      efficacious than nearly all comparators. Most treatments had noninferior
      treatment continuation compared to placebo, except oxcarbazepine, which was
      inferior. Findings were supported by subgroup and sensitivity analyses.
      CONCLUSIONS: Risperidone, serotonin reuptake inhibitors as a class and
      dextromethorphan/quinidine demonstrated evidence of efficacy for agitation in
      dementia, although findings for dextromethorphan/quinidine were based on a single
      RCT. Our findings do not support prescribing haloperidol due to lack of efficacy,
      or oxcarbazepine due to lack of acceptability. The decision to prescribe should
      be based on comprehensive consideration of the benefits and risks, including
      those not evaluated in this meta-analysis.

PMID- 29637596
TI  - Trends in prevalence of thinness, overweight and obesity among Swedish children
      and adolescents between 2004 and 2015.
AB  - AIM: This study explored weight trends among children aged 4, 7, 11, 14 and 17
      years in Jonkoping County Sweden, from 2004 to 2015. METHODS: The study had a
      repeated cross-sectional design, and body mass index (BMI) was calculated based
      on height and weight measurements collected from child health and school health
      records. The prevalence of thinness, overweight and obesity was estimated with
      international cut-offs, with linear trends calculated separately for boys and
      girls. RESULTS: There were 190 965 measurements of BMI and these covered 82-97%
      of the younger children and 55-69% of the older children during the study period.
      The prevalence of thinness varied between 0.2% and 2.2% across time and age
      groups and did not change over the study period. There was a small decrease in
      overweight among both girls and boys aged four years. There were increasing
      trends in overweight and obesity in both girls and boys aged 11 and 14 years of
      age and a sharp increase among 17-year-old boys, with 7.3% obese in 2014/2015 and
      3.6% in 2004/2005. CONCLUSION: The prevalence of obesity decreased from 2004 to
      2015 or was stable in younger Swedish children, but increased among older
      children, with a large increase in adolescent boys.

PMID- 29637599
TI  - Metastatic tumor cells detection and anti-metastatic potential with vesicular
      stomatitis virus in immunocompetent murine model of osteosarcoma.
AB  - Sarcomas are associated with a high incidence of lung metastasis, which leads to
      a high-risk of cancer death. This study was performed to explore the pre-clinical
      theranostic potential of a novel fully functional recombinant vesicular
      stomatitis virus carrying imaging gene Katushka (rVSV-K), as virotherapy and
      circulating tumor cells (CTCs) detection in the syngeneic mouse model of
      osteosarcoma with spontaneous pulmonary metastases. Recombinant VSV-K was
      generated and evaluated in vitro on human and murine osteosarcoma cells.
      Spontaneous osteosarcoma metastases were established in immune-competent mice by
      implanting subcutaneously syngeneic osteosarcoma LM8 cells. The vector was
      injected into the tumor-bearing mice via jugular vein either once or repeatedly.
      To assess effectiveness, primary tumor growth and development of lung metastasis
      as well as survival were evaluated. We found that rVSV-K efficiently replicated
      in and killed all osteosarcoma cell lines in time-dependent manners. Both single
      or repeated systemic injections of the virus did not inhibit the growth of the
      primary tumor, but the repeated administration could effectively suppress the
      development of lung metastases and was likely responsible for the observed
      increase in survival. Furthermore, we demonstrated, for the first time, that CTCs
      in blood samples from syngeneic osteosarcoma-bearing mice were successfully
      detected by utilizing rVSV-K ex vivo. Our results show that repeated systemic
      injections of rVSV-K are an effective anti-metastatic agent against osteosarcoma
      in immune-competent mice and this virus to be a useful tool for detection of
      osteosarcoma CTCs, suggesting that further development of future viral-based
      theranostic approach in patients with osteosarcoma is warranted. (c) 2018
      Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
      36:2562-2569, 2018.

PMID- 29637597
TI  - Ablation of Dnmt3b in chondrocytes suppresses cell maturation during embryonic
      development.
AB  - DNA methylation is a major mode of epigenetic regulation in the mammalian genome
      and is essential for embryonic development. The three catalytic DNA
      methyltransferases (Dnmts), Dnmt1, Dnmt3a, and Dnmt3b, catalyze the methylation
      of cytosine. Dnmt3b is highly expressed in chondrocytes and global knockout of
      Dnmt3b led to skeletal deformations and embryonic lethality, suggesting an
      essential role of Dnmt3b in endochondral bone formation. To further define the
      role of Dnmt3b in skeletal development, Dnmt3b was deleted in Col2 positive
      chondrocyte lineage cells. Both axial and appendicular skeletal size were reduced
      and bone mineralization was delayed in Col2Cre+ ;Dnmt3bf/f (Dnmt3bCol2 ) mice at
      E14.5 and E18.5. While Alcian Blue Hematoxylin/Orange G (ABH/OG) staining showed
      normal chondrocyte columns in control growth plates, the length of hypertrophic
      chondrocyte zone and type X collagen expression were decreased in E18.5 growth
      plates from Dnmt3bCol2 mice. TUNEL and PCNA staining demonstrated that the delay
      in chondrocyte maturation observed in the Dnmt3bCol2 growth plates was not
      secondary to altered chondrocyte apoptosis or proliferation. Complementary in
      vitro experiments were performed on primary sternal chondrocytes isolated from
      control and Dnmt3bCol2 mice. Gene expression studies confirmed delayed terminal
      maturation as Mmp13 and Col10a1 expression was down-regulated in Dnmt3bCol2
      chondrocytes. In addition, alkaline phosphatase (ALP) and Alizarin Red staining
      confirmed that Dnmt3b deletion in chondrocytes delays in vitro chondrocyte
      hypertrophic differentiation and matrix mineralization. Mechanistically, Dnmt3b
      gene deletion resulted in decreased BMP signaling through reduction of Smad1
      phosphorylation. These findings show that epigenetic factor, Dnmt3b is necessary
      for normal chondrocyte hypertrophic maturation and limb development.

PMID- 29637600
TI  - The involvement of Kav001 in inhibition of LPS/P. gingivalis-induced.
AB  - TNF-a is an important cytokine mediator of inflammation which suggests that
      inhibition of TNF activity may provide potential for clinical application. Recent
      data indicated that treatment of both human and mouse cells with Kavain
      significantly modulates P. gingivalis- and LPS-induced TNF-alpha expression. In
      order to obtain a selective analog with optimized biological activity and
      structural physico-chemical properties of Kavain, Kavain analogs were designed
      and synthesized and found one Kavain analogue (named Kav001) that is similar to
      Kavain but soluble and does not induce a significant toxicity. Both studies in
      vitro and in vivo treatment by Kav001 showed stronger biological function as
      compared to Kavain. Furthermore, most mouse bone marrow macrophages up-regulated
      Bcl-6 while down-regulating LITAF expression after treatment with Kav001 for 36
      h. Consequently, this led to an extension of macrophage pseudopods due to its
      immune response to P.g. infection/LPS stimulation.

PMID- 29637601
TI  - Blood pressure and risk of incident Alzheimer's disease dementia by
      antihypertensive medications and APOE epsilon4 allele.
AB  - OBJECTIVE: To examine the association of blood pressure (BP) with incident
      Alzheimer's disease (AD) dementia. METHODS: This work is based on a longitudinal,
      cohort study of 18 years, the Chicago Health and Aging Project (CHAP) performed
      in 2,137 participants (55% black) with systolic BP measured around 8.1 years
      before incident AD dementia. RESULTS: The association of BP with risk of AD
      dementia was U-shaped, with the lowest risks of AD dementia near the center of
      the systolic BP (SBP) and diastolic BP (DBP) distributions, and modestly elevated
      risk at lower BPs, and greater risk at higher BPs. The degree of U-shape and the
      range of lowest risk (threshold ranges) varied with antihypertensive medication
      use and presence of the APOE epsilon4 allele. The U-shape was most prominent for
      the subgroup not taking antihypertensive medications and having an APOE epsilon4
      allele. At higher BPs, those having the APOE epsilon4 allele and not receiving
      antihypertensive medication were at greater risk of AD dementia than other
      groups: The risk of incident AD dementia increased by 100% (relative risk [RR] =
      2.00; 95% confidence interval [CI] = 1.70, 2.31) for every 10 mm Hg increase in
      SBP above 140 mm Hg. For DBP, the risk of incident of AD dementia increased by
      57% (RR = 1.57; 95% CI = 1.33, 1.86) for every 5 mm Hg increase in DBP above 76
      mm Hg. INTERPRETATION: The BP risk of AD dementia association is U-shaped, with
      elevated risk at lower and higher BPs. People having the APOE epsilon4 allele and
      not receiving antihypertensive medication with higher BPs have notably elevated
      risk of AD dementia. Ann Neurol 2018;83:935-944.

PMID- 29637602
TI  - Significance of Notch and Wnt signaling for chemoresistance of colorectal cancer
      cells HCT116.
AB  - 5-fluorouracil (5-FU) and oxaliplatin (OxaPt) are the main chemotherapeutics for
      colorectal cancer (CRC). Chemotherapy response rates for advanced CRC remain low,
      primarily due to intrinsic or acquired chemoresistance. The importance of Notch
      and Wnt signaling for carcinogenesis of CRC as well as crosstalk of Notch and Wnt
      signaling with many oncogenic signaling pathways suggest that Notch and Wnt
      pathways could be responsible for chemoresistance. In this study, we compared
      changes in Notch and Wnt signaling after 5-FU and OxaPt treatment in CRC cells
      HCT116 and its chemoresistant sublines HCT116/FU and HCT116/OXA. The levels of
      Notch1 receptor intracellular domain NICD1 and non-phosphorylated beta-catenin,
      the reporters of Notch and Wnt signaling, were upregulated in untreated
      chemoresistant HCT116/FU and HCT116/OXA cells. Our data suggest that Notch
      inhibitor RO4929097 (RO) and Wnt inhibitor XAV939 (XAV) enhance the survival
      potential of OxaPt-treated cells. The protein level of Notch target gene HES1 was
      significantly upregulated in chemoresistant HCT116/FU and HCT116/OXA cells,
      compared to HCT116. HES1 silencing increased viability of HCT116 and its
      chemoresistant sublines after 5-FU or OxaPt treatment. The results of HES1
      downregulation coincide with RO and XAV effects on cell viability of OxaPt
      treated cells.

PMID- 29637603
TI  - A possible connection between childhood pain, joint hypermobility and
      Neurodevelopmental disorders.

PMID- 29637604
TI  - Funding research to change lives: exploring the impact of Diabetes UK research.

PMID- 29637605
TI  - Epidemiology of autoimmune versus infectious encephalitis.

PMID- 29637606
TI  - Development problems were common five years after positive screening for language
      disorders and, or, autism at 2.5 years of age.
AB  - AIM: This study identified whether children who had screened positive for either
      developmental language disorder (DLD) or autism spectrum disorder (ASD) at the
      age of 2.5 years had neurodevelopmental assessments five years later. METHODS:
      Our study cohort were 288 children born from 1 July 2008 to 20 June 2009 who
      screened positive for DLD and, or, ASD at 2.5 years. Of these, 237 children were
      referred to, and assessed, at the Paediatric Speech and Language Pathology clinic
      (n = 176) or the Child Neuropsychiatry Clinic (n = 61) at the Queen Silvia
      Children's Hospital, Gothenburg, Sweden. Clinical registers covering all relevant
      outpatient clinics were reviewed five years later with regard to established
      diagnoses. RESULTS: When the 237 were followed up five years later, 96 (40%) had
      established neurodevelopmental disorders or problems, often beyond DLD and ASD.
      Co-existing problems were common in this cohort and multidisciplinary assessments
      were indicated. The other 60% did not appear in subsequent clinic records. It is
      likely that this 40% was a minimum rate and that more children will be referred
      for developmental problems later. CONCLUSION: Five years after they had been
      screened positive for DLD and, or autism at 2.5 years, 40% of our cohort had
      remaining or other developmental problems.

PMID- 29637608
TI  - Sotagliflozin: a dual sodium-glucose co-transporter-1 and -2 inhibitor for the
      management of Type 1 and Type 2 diabetes mellitus.
AB  - AIMS: To evaluate the evidence for the novel dual sodium-glucose co-transporter-1
      (SGLT1) and -2 (SGLT2) inhibitor, sotagliflozin, which may enhance the efficacy
      of SGLT2 inhibitors by additionally reducing intestinal glucose absorption.
      METHODS: The search terms 'sotagliflozin', 'LX4211', 'SGLT' and 'diabetes' were
      entered into PubMed. Evidence for the pharmacokinetics, pharmacodynamics, safety
      and efficacy of sotagliflozin in Type 1 and 2 diabetes was extracted from the
      retrieved literature, critically evaluated, and contextualized in relation to
      data on existing SGLT2 inhibitors. RESULTS: There is convincing evidence from a
      range of phase II and III clinical trials that sotagliflozin significantly
      improves glycaemic control in both Type 1 and Type 2 diabetes. Additional
      benefits, such as smaller postprandial plasma glucose excursions, lower insulin
      requirements, appetite suppression and weight loss have been documented. While
      this is encouraging, several safety concerns remain; a dose-dependent increase in
      the rate of diabetic ketoacidosis, diarrhoea and genital mycotic infection is
      apparent, although statistical exploration of the data regarding such events is
      currently lacking. Speculatively, use of a 200-mg rather than a 400-mg dose may
      help to limit unwanted effects. CONCLUSIONS: The current evidence for
      sotagliflozin in diabetes appears promising. Further studies sufficiently powered
      to assess present and emerging safety concerns, as well as to identify
      individuals for whom sotagliflozin may be of particular benefit/harm would now be
      informative for regulatory decision-making. Direct comparisons with existing
      SGLT2 inhibitors are also needed to determine relative safety/efficacy profiles
      for the different indications.

PMID- 29637609
TI  - MicroRNA-29a regulates neural stem cell neuronal differentiation by targeting
      PTEN.
AB  - Neural stem cells (NSCs) are self-renewing, pluripotent, and undifferentiated
      cells which have benefits as candidates for central nervous system (CNS) injury.
      However, the transplanted NSCs usually maintain their undifferentiated
      characteristics, or differentiated potentially along the glial lineage after
      transplantation. MicroRNAs (miRNAs) are small, non-coding RNAs that play key
      roles in cell differentiation. However, it is unknown whether miR-29a could play
      a role in the process of NSC's differentiation. Primary NSCs were derived from
      rat embryonic cortex. Lentiviral vector-mediated miR-29a (LV-miR-29a) and
      negative control (LV-null) were infected into NSCs. Quantitative real-time PCR
      was used to detect expression of miR-29a and PTEN. Immunocytochemistry was used
      to stain neurons, astrocytes, and oligodendrocytes. Dual luciferase assay to
      study the interaction between miR-29a and PTEN. The current study showed that the
      expression of miR-29a was upregulated during NSC differentiation, while the
      expression of PTEN was downregulated during NSC differentiation. After infection
      with LV-miR-29a, MAP-2-positive neurons significantly increased, and GFAP
      positive astrocytes significantly decreased. Furthermore, we demonstrated that
      PTEN is a molecular target of miR-29a. miR-29a promote the neuronal
      differentiation and decrease the astrocytes differentiation of NSCs via targeting
      PTEN. This may give insight into a novel mechanism of NSC differentiation and
      provide a promising therapeutic target.

PMID- 29637607
TI  - Overexpression of antimicrobial peptides contributes to aging through cytotoxic
      effects in Drosophila tissues.
AB  - The innate immune response tends to become hyperactive and proinflammatory in
      older organisms. We investigated connections between activity of the immune
      related genes and aging using the Drosophila model. A hallmark of Drosophila
      immunity is the production of antimicrobial peptides (AMP), whose expression is
      triggered via activation of the Toll and Imd immune pathways and regulated by NF
      KB-like transcription factors, Dif/Dorsal and Relish. It was previously shown
      that overexpression of the upstream component of the immune pathways shortens
      lifespan via activation of the Relish-dependent immune response. Here we show
      that direct overexpression of the Relish target AMP genes broadly at high levels
      or in the fat body induced apoptosis, elicited depolarization of the mitochondria
      and significantly shortened lifespan. Underexpression of Relish in the fat body
      beginning in the second half of lifespan prevented overactivation of AMPs and
      extended longevity. Unlike infection-induced responses, the age-related increase
      in AMPs does not require the upstream recognition/transduction module of the Imd
      pathway. It does however require downstream elements, including Relish and Ird5,
      a component of the downstream IKK complex. Together, these results established
      causal links between high-level production of antimicrobial peptides and
      longevity.

PMID- 29637610
TI  - Fibril deformation under load of the rabbit Achilles tendon and medial collateral
      ligament femoral entheses.
AB  - Microscopic visualization under load of the region connecting ligaments/tendons
      to bone, the enthesis, has been performed previously; however, specific
      investigation of individual fibril deformation may add insight to such studies.
      Detailed visualization of fibril deformation would inform on the mechanical
      strategies employed by this tissue in connecting two mechanically disparate
      materials. Clinically, an improved understanding of enthesis mechanics may help
      guide future restorative efforts for torn or injured ligaments/tendons, where the
      enthesis is often a point of weakness. In this study, a custom ligament/tendon
      enthesis loading device was designed and built, a unique method of sample
      preparation was devised, and second harmonic and two-photon fluorescence
      microscopy were used to capture the fibril-level load response of the rabbit
      Achilles tendon and medial collateral ligament femoral entheses. A focus was
      given to investigation of the mechanical problem of fibril embedment. Resultant
      images indicate a rapid (occurring over approximately 60 MUm) change in fibril
      orientation at the interface of ligament/tendon and calcified fibrocartilage
      early in the loading regime, before becoming relatively constant. Such a change
      in fibril angle helps confirm the materially graded region demonstrated by
      others, while, in this case, providing additional insight into fibril bending. We
      speculate that the scale of the mechanical problem (i.e., fibril diameters being
      on the order of 250 nm) allows fibrils to bend over the small (relative to the
      imaging field of view, but large relative to fibril diameter) distances observed;
      thus, potentially lessening required embedment lengths. Nevertheless, this
      behavior merits further investigation to be confirmed. (c) 2018 Orthopaedic
      Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2506-2515,
      2018.

PMID- 29637611
TI  - The changing face of hematopoiesis: a spectrum of options is available to stem
      cells.
AB  - For more than 30 years, the scheme whereby bone marrow hematopoietic stem cells
      give rise to the many different types of blood and immune cells has been
      represented as a lineage tree diagram. In this model, hematopoietic stem cells
      follow a preferred route to each of the end-cell types and gradually restrict
      their other lineage options via a series of intermediate oligo-potent
      progenitors. Recent findings of lineage biases or affiliations within
      hematopoietic stem and progenitor cells that are either pluripotent or uni-potent
      show that a continuum of fate options is open to hematopoietic stem cells. These
      results support the view that in order to close down developmental options,
      hematopoietic stem cells can make an immediate lineage choice rather than become
      gradually committed as they progress step-wise through a series of intermediate
      progenitors. In this scenario, there is inherent versatility in that developing
      cells are still able to move sideways to adopt an alternative lineage fate. Here,
      we examine the information that is leading toward this very different viewpoint
      of blood cell development.

PMID- 29637612
TI  - A preliminary study of growth characteristics of melanocytes co-cultured with
      keratinocytes in vitro.
AB  - To clarify the characteristic growth of melanocytes (MCs) and Keratinocytes (KCs)
      in vitro and discuss the mechanism of culturing autologous melanocytes in the
      treatment of vitiligo. Epidermis cells derived from normal skin tissues were
      isolated and cultured in vitro. Melanocytes in DOPA staining were observed. The
      expression level of markers in MCs was detected by qRT-PCR and the percentage of
      MCs and KCs were detected by flow cytometry. Cells derived from normal skin
      tissues mainly included KCs, MCs, and fibroblasts. There were significant
      differences between the percentage of KC, MC, fibroblasts (P < 0.05), and the
      expression of Microphthalmia-associated transcription factor (P < 0.05) and
      Tyrosinase-related protein-2 (P < 0.05) in the second, 10th, 20th, and 30th day.
      Significant differences were also found between the average numbers of MC stained
      by DOPA (P < 0.05) and the average percentage of MCs in the 10th, 20th, and 30th
      Day (P < 0.05). But there were no significant differences between the average
      percentage of KCs in the 10th, 20th, and 30th Day (P > 0.05) detected by flow
      cytometry. The number of MCs co-cultured with KCs in vitro reached the maximum in
      the 20th Day and this co-cultured model may contribute to the growth of MCs which
      could be used in the treatment of vitiligo.

PMID- 29637613
TI  - Dual silencing of EGFR and HER2 enhances the sensitivity of gastric cancer cells
      to gefitinib.
AB  - Gefitinib exhibits very limited efficacy in gastric cancer (GC). Indeed, the
      limited clinical results obtained with gefitinib alone justify investigation of
      additional therapeutic strategies. Here, we demonstrate the importance of EGFR
      and HER2 in GC malignancy using RNA interference (RNAi). Additionally, we
      explored the ability of RNAi targeting EGFR and HER2 to enhance the sensitivity
      of GC cells to gefitinib. Specific small interfering RNAs (siRNAs) significantly
      inhibited mRNA and protein expression of target genes. EGFR-specific siRNA,
      EGFR/HER2 siRNAs, and gefitinib inhibited growth and induced apoptosis in GC cell
      lines in a dose-dependent manner. In contrast, resistance to HER2-siRNA-induced
      growth inhibition and apoptosis was linked to compensatory activation of EGFR.
      Moreover, gefitinib dramatically reduced p-EGFR and p-HER2 levels in the cell
      lines tested, and sensitivity to gefitinib was enhanced through dual silencing of
      EGFR and HER2 via suppression of AKT and ERK activation. These findings are in
      agreement with the profound inhibitory effect of gefitinib on activation of both
      EGFR and HER2. Overall, EGFR/HER2 knockdown by siRNAs further decreased the
      growth of GC cells treated with gefitinib alone, confirming that single-agent
      drug targeting does not achieve a maximal biological effect. The combination of
      gefitinib with EGFR/HER2 siRNAs should be further investigated as a new strategy
      for the treatment of GC and other EGFR/HER2-dependent cancers.

PMID- 29637614
TI  - Development of stability indicating HPLC method for the separation and validation
      of enantiomers of miconazole.
AB  - A selective and sensitive stability indicting HPLC method was developed for the
      analysis of enantiomers of miconazole. For this purpose, six different
      polysaccharide-based chiral columns were evaluated. Optimization was performed
      using several polar organic and alcohol-hydrocarbon mobile phases. As a result of
      optimization studies, the analysis was carried out using Lux Cellulose-3,
      methanol as a mobile phase at a flow rate of 1 mL.min-1 , and the detection
      wavelength was arranged to 230 nm. Developed method has been fully validated
      according to International Council on Harmonization guidelines. Method was found
      linear in the concentration range of 1 to 200 MUg.mL-1 . Coefficient of
      determination (R2 ) was calculated as 0.9996, intraday precision of the method
      was found with the RSD% of 0.56, and the recovery of the method was calculated
      close to 100%. Furthermore, some other validation parameters like specificity,
      selectivity, LOD, and LOQ were also investigated. Stability indicating capability
      of this method was shown by forced degradation studies, and the run time for each
      analysis was less than 6 minutes. As a result, simple, fast, reliable HPLC method
      was developed for the separation and determination of the enantiomers of
      miconazole. Applicability of the developed method was shown with the application
      of marketed pharmaceutical preparations.

PMID- 29637615
TI  - Cardiomyogenic differentiation of human adipose-derived mesenchymal stem cells
      transduced with Tbx20-encoding lentiviral vectors.
AB  - Ischemic heart disease often results in myocardial infarction and is the leading
      cause of mortality and morbidity worldwide. Improvement in the function of
      infarcted myocardium is a main purpose of cardiac regenerative medicine. One
      possible way to reach this goal is via stem cell therapy. Mesenchymal stem cells
      (MSCs) are multipotent stromal cells that can differentiate into a variety of
      cell types but display limited cardiomyogenic differentiation potential. Members
      of the T-box family of transcription factors including Tbx20 play important roles
      in heart development and cardiomyocyte homeostasis. Therefore, in the current
      study, we investigated the potential of Tbx20 to enhance the cardiomyogenic
      differentiation of human adipose-derived MSCs (ADMSCs). Human ADMSCs were
      transduced with a bicistronic lentiviral vector encoding Tbx20 (murine) and the
      enhanced green fluorescent protein (eGFP) and analyzed 7 and 14 days post
      transduction. Transduction of human ADMSCs with this lentiviral vector increased
      the expression of the cardiomyogenic differentiation markers ACTN1, TNNI3, ACTC1,
      NKX2.5, TBX20 (human), and GATA4 as revealed by RT-qPCR. Consistently,
      immunocytological results showed elevated expression of alpha-actinin and cardiac
      troponin I in these cells in comparison to the cells transduced with control
      lentiviral particles coding for eGFP alone. Accordingly, forced expression of
      Tbx20 exerts cardiomyogenic effects on human ADMSCs by increasing the expression
      of cardiomyogenic differentiation markers at the RNA and protein level.

PMID- 29637616
TI  - ATG12 expression quantitative trait loci associated with head and neck squamous
      cell carcinoma risk in a Chinese Han population.
AB  - Autophagy is an essential process to maintain cellular homeostasis and functions,
      which has been demonstrated to play an important role in the different stages of
      tumorigenesis. To evaluate whether the genetic variants in autophagy-related
      genes influence the head and neck squamous cell carcinoma (HNSCC) risk, we
      conducted a case-control study to analyze 11 tagging single nucleotide
      polymorphisms (SNPs) of three core autophagosome formation genes (ATG5, ATG12,
      and ATG16L1) with 576 HNSCC cases and 1552 healthy controls among Chinese
      population. Finally, we identified that rs26537 of ATG12 (additive model:
      adjusted odds ratio [OR] = 1.19, 95% confidence interval [CI] = 1.03-1.37, P =
      0.017) and rs4663402 in ATG16L1 (additive model: adjusted OR = 1.39, 95%CI = 1.08
      1.80, P = 0.010) were significantly associated with the increased risk of HNSCC.
      However, no association was detected between other SNPs and HNSCC risk. The
      results of expression quantitative trait loci (eQTL) analysis based on Genotype
      Tissue Expression (GTEx) accessible data, showed that the risk allele of rs26537
      was significantly associated with up-regulated expression of ATG12 (P = 0.0021).
      Further luciferase activity assay indicated that rs26537 T > C in ATG12 intron
      one region significantly enhanced transcription activity. These results suggested
      that ATG12 eQTL SNP rs26537 might contribute to an allele-specific effect on the
      expression of host gene ATG12 and explain a fraction of HNSCC genetic
      susceptibility.

PMID- 29637618
TI  - From the Editors.

PMID- 29637619
TI  - The impact of transarterial chemoembolization induced complications on outcomes
      after liver transplantation: A propensity-matched study.
AB  - BACKGROUND: Loco-regional complications of transarterial chemoembolization (TACE)
      may adversely affect technical aspects of the liver transplantation (LT). This
      study reviewed the impact of those complications on postoperative outcomes
      encompassing implications on graft selection. METHODS: A retrospective,
      propensity score matching (1:1) analysis accounting for donor and recipient
      confounders was performed on a dataset of patients undergoing LT for
      hepatocellular carcinoma. Outcomes of patients who had TACE (TACE-group) were
      compared with those who did not (NoTACE-group). RESULTS: A total of 57 matched
      pairs were analyzed. TACE achieved effective tumor control (Pre-TACE vs Post
      TACE; Median: 44 mm [interquartile range: 43-50] vs 17 mm [0-36]; P = .002) on
      imaging follow-up. TACE group had, at the hepatectomy, higher incidence of
      ischemia-related complications (adhesions of the necrotic tumor, cholecystitis,
      and/or bile duct necrosis) (40.4% vs 10.5%; P = .001). Overall major post-LT
      complications rate (Dindo-Clavien >=3) were similar (P = .134). Those in the TACE
      group with donors after circulatory death (DCD) had 4.6% 90-day mortality and
      54.3% major complication rate compared to 6.9% and 77.3% (P = .380 and P = .112,
      respectively). CONCLUSION: TACE was an effective bridging procedure that may
      complicate LT inducing ischemic-related complications; nevertheless, it has not
      shown repercussions on mortality or morbidity after the procedure, even using
      donors after circulatory death.

PMID- 29637617
TI  - Transoral endoscopic examination of head and neck region.
AB  - Transoral endoscopy with narrow band imaging (NBI) is useful for early detection
      of head and neck (HN) cancer. However, the lateral and anterior walls of the
      oropharynx, postcricoid area, and posterior wall of the hypopharynx are difficult
      to observe using transoral endoscopy. Advanced cancers in these regions may be
      missed even when NBI is used. This report highlights a method of transoral
      endoscopic examination of the HN region. For observation of the oral cavity and
      oropharynx, it is important to observe these regions without using a mouthpiece.
      Wide opening of the mouth facilitates observation of the oral cavity and
      oropharynx. Moreover, visibility of the oropharynx, including the anterior wall,
      is dramatically improved, when the patient positions the tongue forward and says
      'aaah.' This technique also facilitates observation of the dorsum of the tongue,
      which is difficult to observe from a tangential view when using a mouthpiece. To
      observe the hypopharynx, the Valsalva maneuver is very useful. Patient
      cooperation is important when observing the HN region thoroughly to gain clear
      endoscopic views. Narcotic drugs, such as pethidine hydrochloride, are ideal for
      conscious sedation and reduce the gag reflex while still allowing patient
      cooperation. From the oral cavity to the hypopharynx, including the lateral and
      anterior walls of the oropharynx, postcricoid area, and posterior wall of the
      hypopharynx, most of the HN region can be observed during routine examination
      using transoral endoscopy without any special devices.

PMID- 29637620
TI  - CFAI-Plus: Adding cognitive frailty as a new domain to the comprehensive frailty
      assessment instrument.
AB  - OBJECTIVES: Cognitive frailty is characterized by the presence of cognitive
      impairment in exclusion of dementia. In line with other frailty domains,
      cognitive frailty is associated with negative outcomes. The Comprehensive Frailty
      Assessment Instrument (CFAI) measures 4 domains of frailty, namely physical,
      psychological, social, and environmental frailty. The absence of cognitive
      frailty is a limitation. METHOD: An expert panel selected 6 questions from the
      Informant Questionnaire on Cognitive Decline that were, together with the CFAI
      and the Montreal cognitive assessment administered to 355 older community
      dwelling adults (mean age = 77). RESULTS: After multivariate analysis, 2
      questions were excluded. All the questions from the original CFAI were
      implemented in a principal component analysis together with the 4 cognitive
      questions, showing that the 4 cognitive questions all load on 1 factor,
      representing the cognitive domain of frailty. By adding the cognitive domain to
      the CFAI, the reliability of the adapted CFAI (CFAI-Plus), remains good
      (Cronbach's alpha: .767). CONCLUSIONS: This study showed that cognitive frailty
      can be added to the CFAI without affecting its good psychometric properties. In
      the future, the CFAI-Plus needs to be validated in an independent cohort, and the
      interaction with the other frailty domains needs to be studied.

PMID- 29637621
TI  - Assessment of sediment mutagenicity in areas under the influence of a
      contaminated site undergoing a remediation process.
AB  - Soil contamination enters aquatic ecosystems affecting sediment quality. The
      region studied is the Taquari River, Brazil, close to a site contaminated by wood
      preservatives, with a runoff route into the river. The first stage of the
      remediation process (In this article, the terms intervention and remediation have
      been used with slightly different meanings. We consider intervention to be the
      first phase of the remediation process, which aims to remove active sources) was
      an intervention to remove the main active sources. The Salmonella/microsome assay
      and polycyclic aromatic hydrocarbons (PAHs) were used to assess sediment quality
      in organic extracts during different intervention phases. The strains used were
      TA98, TA97a, and TA100 with and without S9mix (+/-S9). The results indicated the
      presence of pro-mutagens at site Ta010 (closest to the contaminated site) in all
      samplings, and the highest result occurred before intervention for TA100 + S9
      (1,672 +/- 215.9 rev/g). These values decreased during (83 +/- 23.6 rev/g) and
      after this process (403 +/- 105.9 rev/g), although the PAHs concentrations
      increased. Samples from this site presented PAHs with a carcinogenic potential
      during the assessed periods. After intervention, Ta006 (4 km downstream from
      Ta010) showed the most significant mutagenesis for TA100 + S9 (764 +/- 230.2
      rev/g) and, although the total PAHs values were lower, the species considered
      carcinogenic had higher concentrations. Mutagenesis predicted values of PAHs
      confirmed that carcinogenic species were predominantly detected by TA100, and the
      other PAHs by TA97a strains. Marked contaminant release to the river was
      observed, mainly in Ta010 at different periods. Mutagenicity and PAHs values in
      an internal stream, upstream from Ta010, showed a dispersion route of these
      agents. Thus, contamination in Ta010 and possible contribution to Ta006, after
      intervention, provides a warning regarding environmental quality in the region.
      Environ. Mol. Mutagen. 59:625-638, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29637622
TI  - Hypomagnesemia During Teriparatide Treatment in Osteoporosis: Incidence and
      Determinants.
AB  - In our clinical experience, we have encountered patients who developed
      hypomagnesemia after the introduction of teriparatide. Some trials have reported
      hypomagnesemia as an adverse event during teriparatide treatment, but this issue
      had never been studied specifically. Our objective was twofold: 1) determine the
      incidence of hypomagnesemia (serum magnesium <0.7 mmol/L) associated with
      teriparatide in a retrospective cohort and 2) identify the predisposing factors
      to hypomagnesemia in this cohort. We reviewed the files of 53 patients treated
      for severe osteoporosis with teriparatide for 6 to 24 months between May 2008 and
      January 2016. Serum magnesium levels were measured at 0, 3, 6, 12, 18, and 24
      months. In the full cohort, we observed an average decrease of serum magnesium of
      0.075 mmol/L, 0.069 mmol/L, 0.085 mmol/L, 0.086 mmol/L (p < 0.001) at 3, 6, 12
      months, and at the end of the treatment, respectively. The cumulative incidence
      of hypomagnesemia during treatment with teriparatide was 35.9% (19 patients).
      Patients' older age (71.1 versus 65.1 years; p = 0.05) and lower baseline level
      of magnesium before teriparatide treatment (0.81 mmol/L versus 0.85 mmol/L; p =
      0.03) were significant risk factors for teriparatide-induced hypomagnesemia. The
      average decrease of serum magnesium was greater in the patients who developed
      hypomagnesemia compared with normomagnesemic patients at 3 months (0.110 mmol/L
      versus 0.054 mmol/L; p = 0.02), 6 months (0.139 mmol/L versus 0.036 mmol/L; p <
      0.001), and 12 months (0.156 mmol/L versus 0.048 mmol/L; p < 0.001). Serum
      calcium, creatinine, and parathyroid hormone remained normal throughout the
      treatment period. We observed a statistically significant decrease in the serum
      magnesium levels in patients treated with teriparatide for severe osteoporosis.
      Older age and lower baseline magnesium were significant determinants of
      hypomagnesemia. Closer monitoring of serum magnesium level should be considered
      in these patients. (c) 2018 American Society for Bone and Mineral Research.

PMID- 29637623
TI  - Trying to make sense of school shootings: How?

PMID- 29637624
TI  - Quantitative chest CT for subtyping chronic lung allograft dysfunction and its
      association with survival.
AB  - Chronic lung allograft dysfunction (CLAD) is a major cause of mortality in lung
      transplant recipients. CLAD can be sub-divided into at least 2 subtypes with
      distinct mortality risk characteristics: restrictive allograft syndrome (RAS),
      which demonstrates increased overall computed tomography (CT) lung density in
      contrast with bronchiolitis obliterans syndrome (BOS), which demonstrates reduced
      overall CT lung density. This study aimed to evaluate a reader-independent
      quantitative density metric (QDM) derived from CT histograms to associate with
      CLAD survival. A retrospective study evaluated CT scans corresponding to CLAD
      onset using pulmonary function tests in 74 patients (23 RAS, 51 BOS). Two
      different QDM values (QDM1 and QDM2) were calculated using CT lung density
      histograms. Calculation of QDM1 includes the extreme edges of the histogram.
      Calculation of QDM2 includes the central region of the histogram. Kaplan-Meier
      analysis and Cox regression analysis were used for CLAD prognosis. Higher QDM
      values were significantly associated with decreased survival. The hazard ratio
      for death was 3.2 times higher at the 75th percentile compared to the 25th
      percentile using QDM1 in a univariate model. QDM may associate with CLAD patient
      prognosis.

PMID- 29637625
TI  - Genomewide Association Study Identifies Cxcl Family Members as Partial Mediators
      of LPS-Induced Periodontitis.
AB  - Periodontitis (PD) is characterized by bacterial infection and inflammation of
      tooth-supporting structures and can lead to tooth loss. PD affects ~47% of the US
      population over age 30 years and has a heritability of about 50%. Although the
      host immunoinflammatory response and genetic background play a role, little is
      known of the underlying genetic factors. We examined natural genetic variation in
      lipopolysaccharide (LPS)-induced PD across a panel of inbred mouse strains, the
      hybrid mouse diversity panel (HMDP). We observed a strain-dependent sixfold
      difference in LPS-induced bone loss across the HMDP with a heritability of 53%.
      We performed a genomewide association study (GWAS) using FAST-LMM, which corrects
      for population structure, and identified loci significantly associated with PD.
      We examined candidate genes at a locus on chromosome 5, which suggested a
      relationship between LPS-induced bone loss and, together with expression data,
      identified Cxcl family members as associated with PD. We observed an increase in
      Cxcl10 protein, as well as immune cells and pro-inflammatory cytokines in
      C57BL/6J (high bone loss strain) but not in A/J (low bone loss strain) after LPS
      injections. Genetic deletion of CXCR3 (Cxcl9 and10 receptor) demonstrated a ~50%
      reduction in bone loss and reduced osteoclasts after LPS injections. Furthermore,
      WT mice treated with AMG-487 (a CXCR3 antagonist) showed a ~45% reduction in bone
      loss and decreased osteoclasts after LPS injections. We conclude that CXCR3 is a
      strong candidate for modulating the host response in individuals susceptible to
      PD. (c) 2018 American Society for Bone and Mineral Research.

PMID- 29637626
TI  - Reduction in ultraviolet B light-induced erythema by oxymetazoline and
      brimonidine is mediated by different alpha-adrenoceptors.
AB  - When applied topically, oxymetazoline and brimonidine reduce the persistent
      facial erythema of rosacea; this effect is mediated by cutaneous vasoconstriction
      induced by postsynaptic activation of alpha-adrenoceptors. We investigated the
      alpha-adrenergic pharmacology of oxymetazoline and brimonidine. Functional
      activity on alpha-adrenoceptors was evaluated in vitro in HEK293 cells stably
      expressing single receptor subtypes using a fluorometric imaging plate reader
      Ca2+ influx assay. Oxymetazoline was an alpha1 -adrenoceptor agonist with partial
      alpha2 -adrenoceptor activity, whereas brimonidine was a highly selective full
      alpha2 -adrenoceptor agonist. In vivo pharmacology was investigated in a mouse
      model of ultraviolet B light (UVB)-induced skin erythema. To selectively inhibit
      alpha-adrenoceptor subtypes, mice were injected with prazosin (an alpha1 
      selective antagonist) or rauwolscine (an alpha2 -selective antagonist) following
      UVB exposure. Oxymetazoline cream 1.0%, brimonidine gel 0.33% or vehicle control
      was applied topically, and erythema was measured using a chromameter.
      Oxymetazoline and brimonidine reduced UVB-induced erythema compared with vehicle
      control (P < .01). The effect of oxymetazoline was impaired in prazosin
      pretreated but not rauwolscine-pretreated mice. Conversely, the effect of
      brimonidine was impaired in rauwolscine-pretreated but not prazosin-pretreated
      mice. These data suggest that while oxymetazoline and brimonidine produce
      cutaneous vasoconstriction, they do so through different alpha-adrenergic
      mechanisms, with oxymetazoline primarily acting via alpha1 -adrenoceptors and
      brimonidine acting via alpha2 -adrenoceptors.

PMID- 29637627
TI  - Blood brain barrier: A review of its anatomy and physiology in health and
      disease.
AB  - The blood-brain barrier (BBB) is the principal regulator of transport of
      molecules and cells into and out of the central nervous system (CNS). It
      comprises endothelial cells, pericytes, immune cells, astrocytes, and basement
      membrane, collectively known as the neurovascular unit. The development of the
      barrier involves many complex pathways from all the progenitors of the
      neurovascular unit, but the timing of its formation is not entirely known. The
      coordinated activities of all the components of the neurovascular unit and other
      tissues ensure that materials required for growth and maintenance are allowed
      into the CNS while extraneous ones are excluded. This review summarizes current
      knowledge of the anatomy, development, and physiology of the BBB, and alterations
      that occur in disease conditions. Clin. Anat. 31:812-823, 2018. (c) 2018 Wiley
      Periodicals, Inc.

PMID- 29637628
TI  - PKCalpha in colon cancer cells promotes M1 macrophage polarization via MKK3/6-P38
      MAPK pathway.
AB  - Tumor associated macrophages are potential targets of the immune therapy for
      patients with colon cancer. PKCalpha acts as a tumor suppressor in the intestine.
      However, the correlation between PKCalpha expressed in colon cancer cells and
      tumor associated macrophages polarization has never been detected. In the present
      study, the correlation between PKCalpha expression and level of M1 macrophages
      was evaluated in human colon cancer tissues. A xenograft mouse model of colon
      cancer cells with different PKCalpha expression level was constructed to evaluate
      the effect of PKCalpha on M1 macrophages polarization in vivo. Co-culture of
      colon cancer cells and differentiated macrophages was used to detect the
      potential interplay in vitro. PKCalpha regulated production of cytokines which
      correlated with macrophage polarization and the underlying mechanism was further
      explored. Our study showed that high PKCalpha expression in human colon cancer
      tissues correlated with better prognosis and high M1 macrophage content. PKCalpha
      expressed in colon cancer cells inhibited the growth of colon cancer in mice
      model. PKCalpha induced macrophages polarized to the M1-like phenotype both in
      vitro and in vivo. Mechanistically, PKCalpha targeted P38 via MKK3/6 to promote
      IL12 and GM-CSF expression which further enhanced M1-like macrophages
      polarization. In conclusion, this study provided evidence for the first time that
      PKCalpha in colon cancer cells play an anticancer action by inducing the
      polarization of tumor associated macrophages to M1-like phenotype in the tumor
      microenvironment. PKCalpha promoted IL12/GM-CSF-mediated M1 polarization through
      MKK3/6-P38 signaling pathway. Our investigation suggested that modulation of the
      PKCalpha signaling pathway might serve as a novel strategy for colon cancer
      therapy.

PMID- 29637629
TI  - Comments on Filipiak-Pittroff et al.

PMID- 29637630
TI  - Silicon(IV) Corroles.
AB  - Silicon complexes of corrole were obtained for the first time by reaction of the
      free-base corrole with hexachlorodisilane. The peripheral substituents of corrole
      strongly influence the nature of the reaction products: beta-octaalkyl corrole
      was mainly isolated as the MU-oxo dimer, while a hydroxo complex was obtained in
      the case of 5,10,15-tris-(pentafluorophenyl)corrole. In the case of meso-tritolyl
      corrole, a mixture of monomer/MU-oxo dimer was obtained. The silicon corrole
      complexes are more stable toward hydrolysis than the corresponding porphyrin
      derivatives and are endowed with brilliant luminescence properties. The high
      affinity of silicon for fluoride ion allowed investigation of the ability of an
      Si corrole to serve as a sensor for F- detection. The strong color variation due
      to the interaction with the halide ion makes the Si corrole an interesting
      material for the naked-eye detection of inorganic fluoride.

PMID- 29637631
TI  - Suitability of livers for transplantation when treated by normothermic machine
      perfusion.
AB  - BACKGROUND: Many factors may compromise the functional recovery of a harvested
      potential liver for engraftment. Normothermic machine perfusion (NMP) can revive
      hepatic metabolism ex vivo enabling subsequent transplantation. In this study, we
      evaluated the recovery of 11 discarded livers' function utilizing NMP. MATERIALS
      AND METHODS: Eleven consecutive discarded livers underwent NMP for 6 hours. Liver
      function recovery was defined by lactate levels of <=3 mmol/L and continuous bile
      production. RESULTS: Ten of 11 livers perfused were fatty. The median percentage
      of macrosteatosis (MaS) and microsteatosis (MiS) was 40% (10%-90%) and 40% (20%
      50%), respectively, based on a review of paraffin-embedded sections of
      preperfusion biopsies. A discarded "amyloid" liver from an HIV-positive donor was
      also studied. Recovery of liver function was observed in 4 livers, including that
      with the amyloid deposition. These livers sustained shorter cold ischemia times
      and seemed to have increased portal and arterial blood flow. No significant
      change in MiS or MaS was observed before and after perfusion. CONCLUSION: Our
      results suggest that some discarded grafts might have been salvaged for
      transplantation. Further studies utilizing NMP with subsequent transplantation
      would validate this strategy.

PMID- 29637632
TI  - Porous Single-Crystalline CdSe Nanobelts: Cation-Exchange Synthesis and Highly
      Selective Photoelectric Sensing toward Cu2.
AB  - Porous single-crystalline nanostructures are of tremendous interest for their
      application in the catalytic, electronic and sensing fields due to their large
      active surfaces, favorable diffusion, and good electronic transport. Despite the
      recent advances of various other components, photoelectric chalcogenides remain
      almost undeveloped. The present study contributes a facile strategy to prepare
      porous single-crystalline CdSe nanobelts through a cation-exchange reaction, in
      which ZnSe?0.5 N2 H4 hybrid nanobelts are employed as precursors. The detailed
      characterizations indicate the preservation of the belt-like morphology of the
      precursors due to the spatial confinement effect, which arises from the coated
      surfactant layer during the cation-exchange process. Simultaneously, CdSe
      nanobelts with porous and single-crystalline structures are formed following a
      complete exchange between Zn2+ and Cd2+ , the release of N2 H4 , and the atomic
      arrangement. The native photoelectric properties of the as-prepared porous single
      crystalline CdSe nanobelts are systematically addressed based on the nanodevices
      fabricated with a single nanobelt and assembled nanobelt array. The results
      indicate that they present a rapid, stable, and repeatable photoelectric
      response. Moreover, as-prepared nanobelts exhibit highly selective photoelectric
      sensing toward Cu2+ with a low detection limit down to 0.1 ppm. To illuminate
      this phenomenon, a possible sensing mechanism is also discussed.

PMID- 29637633
TI  - Quantifying the Sub-Cellular Distributions of Gold Nanospheres Taken Up by Cells
      through Stepwise, Site-Selective Etching.
AB  - A quantitative understanding of the sub-cellular distributions of nanospheres
      taken up by cells is of key importance to the development of effective
      nanomedicine. With gold nanospheres as a model system, here we demonstrate, for
      the first time, how to quantify the numbers of nanospheres bound to plasma
      membrane, accumulated in cytosol, and entrapped in endo-lysosomes, respectively,
      through stepwise, site-selective etching. Our results indicate that the chance
      for nanospheres to escape from endo-lysosomes is insensitive to the presence of
      targeting ligand although ligand-receptor binding has been documented as a
      critical factor in triggering internalization. Furthermore, the presence of serum
      proteins is shown to facilitate the binding of nanospheres to plasma membrane
      lacking the specific receptor. Collectively, these findings confirm the potential
      of stepwise etching in quantitatively analyzing the sub-cellular distributions of
      nanospheres taken up by cells in an effort to optimize the therapeutic effect.

PMID- 29637634
TI  - Seeding and cross-seeding fibrillation of N-terminal prion protein peptides
      PrP(120-144).
AB  - Prion diseases are infectious neurodegenerative diseases that are capable of
      cross-species transmission, thus arousing public health concerns. Seed-templating
      propagation of prion protein is believed to underlie prion cross-species
      transmission pathology. Understanding the molecular fundamentals of prion
      propagation is key to unravelling the pathology of prion diseases. In this study,
      we use coarse-grained molecular dynamics to investigate the seeding and cross
      seeding aggregation of three prion protein fragments PrP(120-144) originating
      from human (Hu), bank vole (BV), and Syrian hamster (SHa). We find that the seed
      accelerates the aggregation of the monomer peptides by eliminating the lag phase.
      The monomer aggregation kinetics are mainly determined by the structure of the
      seed. The stronger the hydrophobic residues on the seed associate with each
      other, the higher the probability that the seed recruits monomer peptides to its
      surface/interface. For cross-seeding aggregation, we show that Hu has a strong
      tendency to adopt the conformation of the BV seed and vice versa; the Hu and BV
      monomers have a weak tendency to adopt the conformation of the SHa seed. These
      two findings are consistent with Apostol et al.'s experimental findings on
      PrP(138-143) and partially consistent with Jones et al.'s finding on PrP(23-144).
      We also identify several conformational mismatches when SHa cross-seeds BV and Hu
      peptides, indicating the existence of a cross-seeding barrier between SHa and the
      other two sequences. This study sheds light on the molecular mechanism of seed
      templating aggregation of prion protein fragments underlying the sequence
      dependent transmission barrier in prion diseases.

PMID- 29637635
TI  - Soft X-ray Spectroscopy as a Probe for Gas-Phase Protein Structure: Electron
      Impact Ionization from Within.
AB  - Preservation of protein conformation upon transfer into the gas phase is key for
      structure determination of free single molecules, for example using X-ray free
      electron lasers. In the gas phase, the helicity of melittin decreases strongly as
      the protein's protonation state increases. We demonstrate the sensitivity of soft
      X-ray spectroscopy to the gas-phase structure of melittin cations
      ([melittin+qH]q+ , q=2-4) in a cryogenic linear radiofrequency ion trap. With
      increasing helicity, we observe a decrease of the dominating carbon 1 s-pi*
      transition in the amide C=O bonds for non-dissociative single ionization and an
      increase for non-dissociative double ionization. As the underlying mechanism we
      identify inelastic electron scattering. Using an independent atom model, we show
      that the more compact nature of the helical protein conformation substantially
      increases the probability for off-site intramolecular ionization by inelastic
      Auger electron scattering.

PMID- 29637636
TI  - The caveolar membrane system in endothelium: From cell signaling to vascular
      pathology.
AB  - Caveolae are 50- to 100-nm cholesterol and glycosphingolipid-rich flask-shaped
      invaginations commonly observed in many terminally differentiated cells. These
      organelles have been described in many cell types and are particularly abundant
      in endothelial cells, where they have been involved in the regulation of certain
      signaling pathways. Specific scaffolding proteins termed caveolins, along with
      the more recently discovered members of the cavin family, represent the major
      protein components during caveolae biogenesis. In addition, multiple studies
      aimed to investigate the expression and the regulation of these proteins
      significantly contributed to elucidate the role of caveolae and caveolins in
      endothelial cell physiology and disease. The aim of this review is to survey
      recent evidence of the involvement of the caveolar network in endothelial cell
      biology and endothelial cell dysfunction.

PMID- 29637637
TI  - Single breath-hold 3D cardiac T1 mapping using through-time spiral GRAPPA.
AB  - The quantification of cardiac T1 relaxation time holds great potential for the
      detection of various cardiac diseases. However, as a result of both cardiac and
      respiratory motion, only one two-dimensional T1 map can be acquired in one breath
      hold with most current techniques, which limits its application for whole heart
      evaluation in routine clinical practice. In this study, an electrocardiogram
      (ECG)-triggered three-dimensional Look-Locker method was developed for cardiac T1
      measurement. Fast three-dimensional data acquisition was achieved with a spoiled
      gradient-echo sequence in combination with a stack-of-spirals trajectory and
      through-time non-Cartesian generalized autocalibrating partially parallel
      acquisition (GRAPPA) acceleration. The effects of different magnetic resonance
      parameters on T1 quantification with the proposed technique were first examined
      by simulating data acquisition and T1 map reconstruction using Bloch equation
      simulations. Accuracy was evaluated in studies with both phantoms and healthy
      subjects. These results showed that there was close agreement between the
      proposed technique and the reference method for a large range of T1 values in
      phantom experiments. In vivo studies further demonstrated that rapid cardiac T1
      mapping for 12 three-dimensional partitions (spatial resolution, 2 * 2 * 8 mm3 )
      could be achieved in a single breath-hold of ~12 s. The mean T1 values of
      myocardial tissue and blood obtained from normal volunteers at 3 T were 1311 +/-
      66 and 1890 +/- 159 ms, respectively. In conclusion, a three-dimensional T1
      mapping technique was developed using a non-Cartesian parallel imaging method,
      which enables fast and accurate T1 mapping of cardiac tissues in a single short
      breath-hold.

PMID- 29637639
TI  - Highly Enantioselective, Base-Free Synthesis of alpha-Quaternary Succinimides
      through Catalytic Asymmetric Allylic Alkylation.
AB  - The synthesis of diversely substituted five-membered ring succinimide derivatives
      is reported featuring a direct, base-free, palladium-catalyzed asymmetric allylic
      alkylation. The method allows a straightforward access to the desired
      heterocyclic scaffold bearing an all-carbon alpha-quaternary stereogenic center
      in high yields and good to excellent enantioselectivities. To further demonstrate
      the synthetic utility of the method, the allylated products were further
      converted to various versatile chiral building blocks, including a chiral
      pyrrolidine and a spirocyclic derivative, using selective transformations.

PMID- 29637638
TI  - Methodologies for "Wiring" Redox Proteins/Enzymes to Electrode Surfaces.
AB  - The immobilization of redox proteins or enzymes onto conductive surfaces has
      application in the analysis of biological processes, the fabrication of
      biosensors, and in the development of green technologies and biochemical
      synthetic approaches. This review evaluates the methods through which redox
      proteins can be attached to electrode surfaces in a "wired" configuration, that
      is, one that facilitates direct electron transfer. The feasibility of simple
      electroactive adsorption onto a range of electrode surfaces is illustrated, with
      a highlight on the recent advances that have been achieved in biotechnological
      device construction using carbon materials and metal oxides. The covalent
      crosslinking strategies commonly used for the modification and
      biofunctionalization of electrode surfaces are also evaluated. Recent innovations
      in harnessing chemical biology methods for electrically wiring redox biology to
      surfaces are emphasized.

PMID- 29637640
TI  - Mycenaflavin A, B, C, and D: Pyrroloquinoline Alkaloids from the Fruiting Bodies
      of the Mushroom Mycena haematopus.
AB  - Four so far unknown pyrroloquinoline alkaloids, yellow mycenaflavins A, B, and C,
      and the purple mycenaflavin D, have been isolated from the fruiting bodies of
      Mycena haematopus. The structures of these new alkaloids were elucidated by NMR
      spectroscopy and HRMS (ESI+ ). The mycenaflavins are structurally related to
      mycenarubins and haematopodins, which have been previously identified in M.
      haematopus. However, compared with other known fungal pyrroloquinoline alkaloids,
      the mycenaflavins contain an additional double bond within the pyrroloquinoline
      moiety that accounts for the yellow colour of the monomeric mycenaflavins A, B,
      and C. The purple mycenaflavin D is the first known dimeric pyrroloquinoline
      alkaloid with a C-C bridge between the two pyrroloquinoline units. Although the
      minor pyrroloquinoline alkaloid constituent mycenaflavin A exhibits only moderate
      bioactivity against the soil bacterium Azoarcus tolulyticus, the major
      pyrroloquinoline alkaloid constituent haematopodin B is similarly active as the
      antibiotic gentamicin.

PMID- 29637641
TI  - Assessing changes in functional connectivity in a desert bighorn sheep
      metapopulation after two generations.
AB  - Determining how species move across complex and fragmented landscapes and
      interact with human-made barriers is a major research focus in conservation.
      Studies estimating functional connectivity from movement, dispersal or gene flow
      usually rely on a single study period and rarely consider variation over time. We
      contrasted genetic structure and gene flow across barriers for a metapopulation
      of desert bighorn sheep (Ovis canadensis nelsoni) using genotypes collected 2000
      2003 and 2013-2015. Based on the recently observed but unexpected spread of a
      respiratory pathogen across an interstate highway previously identified as a
      barrier to gene flow, we hypothesized that bighorn sheep changed how they
      interacted with that barrier, and that shifts in metapopulation structure
      influenced gene flow, genetic diversity and connectivity. Population assignment
      tests, genetic structure and genetic recapture demonstrated that bighorn sheep
      crossed the interstate highway in at least one location in 2013-2015, sharply
      reducing genetic structure between two populations, but supported conclusions of
      an earlier study that such crossings were very infrequent or unknown in 2000
      2003. A recently expanded population established new links and caused decreases
      in genetic structure among multiple populations. Genetic diversity showed only
      slight increases in populations linked by new connections. Genetic structure and
      assignments revealed other previously undetected changes in movements and
      distribution, but much was consistent. Thus, we observed changes in both
      structural and functional connectivity over just two generations, but only in
      specific locations. Movement patterns of species should be revisited periodically
      to enable informed management, particularly in dynamic and fragmented systems.

PMID- 29637643
TI  - Economic and demographic predictors of dietary variation and nutritional
      indicators in Nicaragua.
AB  - OBJECTIVES: We measured carbon and nitrogen isotopic ratios in a contemporary
      population, and tested how the isotopic variability relates to measures of
      socioeconomic status (e.g., household wealth) and anthropometric measures (e.g.,
      standardized height-for-age and weight-for-age z-scores). METHODS: Hair samples
      from individuals living in the Bosawas Biosphere Reserve in Nicaragua were
      analyzed for delta13 C and delta15 N, and these data were examined in relation to
      individual (e.g., age, sex, anthropometrics) and household (e.g., household size,
      wealth) variables. RESULTS: We found through mixed-effects modeling that delta13
      C and delta15 N varied predictably with individual age and household wealth.
      delta13 C and delta15 N did not, however, improve models predicting variation in
      individual anthropometric measures. CONCLUSION: These results indicate that,
      although there is a relationship between diet (delta13 C and delta15 N) and
      socioeconomic variables, these dietary differences are not the main cause of
      health differences in this population.

PMID- 29637642
TI  - Hyperpolarized ketone body metabolism in the rat heart.
AB  - The aim of this work was to investigate the use of 13 C-labelled acetoacetate and
      beta-hydroxybutyrate as novel hyperpolarized substrates in the study of cardiac
      metabolism. [1-13 C]Acetoacetate was synthesized by catalysed hydrolysis, and
      both it and [1-13 C]beta-hydroxybutyrate were hyperpolarized by dissolution
      dynamic nuclear polarization (DNP). Their metabolism was studied in isolated,
      perfused rat hearts. Hyperpolarized [1-13 C]acetoacetate metabolism was also
      studied in the in vivo rat heart in the fed and fasted states. Hyperpolarization
      of [1-13 C]acetoacetate and [1-13 C]beta-hydroxybutyrate provided liquid state
      polarizations of 8 +/- 2% and 3 +/- 1%, respectively. The hyperpolarized T1
      values for the two substrates were 28 +/- 3 s (acetoacetate) and 20 +/- 1 s (beta
      hydroxybutyrate). Multiple downstream metabolites were observed within the
      perfused heart, including acetylcarnitine, citrate and glutamate. In the in vivo
      heart, an increase in acetylcarnitine production from acetoacetate was observed
      in the fed state, as well as a potential reduction in glutamate. In this work,
      methods for the generation of hyperpolarized [1-13 C]acetoacetate and [1-13
      C]beta-hydroxybutyrate were investigated, and their metabolism was assessed in
      both isolated, perfused rat hearts and in the in vivo rat heart. These
      preliminary investigations show that DNP can be used as an effective in vivo
      probe of ketone body metabolism in the heart.

PMID- 29637644
TI  - Weak IgG self- and hetero-association characterized by fluorescence analytical
      ultracentrifugation.
AB  - Weak protein-protein interactions may be important to binding cooperativity. A
      panel of seven fluorescently labeled tracer monoclonal IgG antibodies, differing
      in variable (V) and constant (C) region sequences, were sedimented in increasing
      concentrations of unlabeled IgGs of identical, similar, and different
      backgrounds. Weak IgG::IgG attractive interactions were detected and
      characterized by global analysis of the hydrodynamic nonideality coefficient, ks
      . The effects of salt concentration and temperature on ks suggest the
      interactions are predominantly enthalpic in origin. The interactions were found
      to be variable in strength, affected by both the variable and constant regions,
      but indiscriminate with respect to IgG subclass. Furthermore, weak attractive
      interactions were observed for all the mAbs with freshly purified human poly-IgG.
      The universality of the weak interactions suggest that they may contribute to
      effector function cooperativity in the normal immune response, and we postulate
      that the generality of the interactions allows for a broader range of epitope
      spacing for complement activation. These studies demonstrate the utility of
      analytical ultracentrifuge fluorescence detection in measuring weak protein
      protein interactions. It also shows the strength of global analysis of
      sedimentation velocity data by SEDANAL to extract hydrodynamic nonideality ks to
      characterize weak macromolecular interactions.

PMID- 29637647
TI  - Copper Promoted Regio- and Stereoselective Aminochlorination of Alkynes and
      Alkenes with NFSI.
AB  - A simple and rapid copper-promoted aminochlorination of unactivated alkynes and
      alkenes with N-fluorobenzenesulfonimide (NFSI) was developed. Two series of
      chloroenamines and chloroamines were obtained in good to high yields. The
      chlorinated enamines could be obtained in a single E configuration. This reaction
      involved a radical process and the CuCl2 acted as the Cl source and NFSI as the N
      source.

PMID- 29637645
TI  - Peer support for physical activity adoption among breast cancer survivors: Do the
      helped resemble the helpers?
AB  - Interventions offering peer mentoring programmes promoting moderate-to-vigorous
      physical activity (MVPA) have shown improvements in MVPA and well-being from
      baseline; however, research is limited. The purpose of this study was to compare
      the physical activity (PA) levels and psychosocial well-being of coaches and
      participants at baseline and following a 12-week intervention. Breast cancer
      survivors (<5 years) were recruited and randomised into either exercise (Reach-to
      Recovery (RTR) + PA) or control (RTR Control). Participants in both groups were
      individually assigned one of the 18 available coaches who delivered either the
      MVPA intervention or the control condition via telephone. PA (7-Day PA Recall),
      psychosocial well-being, fatigue and mood were assessed at baseline and
      intervention completion. Seventy-six breast cancer survivors (average age = 55.62
      (+/-9.55)) were randomised. At baseline, all participants showed significantly
      lower MVPA (p = .001) and well-being (p < .05) as compared to coaches. However,
      post-intervention showed significant improvement in PA and well-being in RTR +
      PA, so that they were no longer significantly different from the coaches. Post
      intervention, MVPA (p < .01), quality of life (p < .05) and fatigue (p < .05)
      remained significantly lower in RTR Controls compared to coaches. Future
      interventions should consider the behavioural patterns not only of the
      participants, but also of those who deliver the interventions.

PMID- 29637648
TI  - Hydrogen Evolution Reactions Catalyzed by a Bis(thiosemicarbazone) Cobalt
      Complex: An Experimental and Theoretical Study.
AB  - The synthesis and characterization of a dinuclear bis(thiosemicarbazone) cobalt
      complex [Co2 L2 (NCS)2 ] is reported. This complex exhibits significant catalytic
      activity for hydrogen production in DMF by using triethylammonium (Et3 NHBF4 ) as
      the proton source. Cyclic voltammetry data allowed a maximum turnover frequency
      of 130 s-1 for 1 m proton concentration to be determined. The catalytic nature of
      the process and the production of dihydrogen were confirmed by gas analysis
      during controlled potential electrolysis experiments. Quantum chemical
      calculations show that the complex displays a ligand-assisted metal-centered
      reactivity and supports a catalytic mechanism involving ligand-based reduction
      and protonation steps followed by metal-centered processes.

PMID- 29637646
TI  - Biophysical characterization and molecular simulation of electrostatically driven
      self-association of a single-chain antibody.
AB  - Colloidal protein-protein interactions (PPI) are often expected to impact key
      behaviors of proteins in solution, such as aggregation rates and mechanisms,
      aggregate structure, protein solubility, and solution viscosity. PPI of an anti
      fluorescein single chain antibody variable fragment (scFv) were characterized
      experimentally at low to intermediate ionic strength using a combination of
      static light scattering and sedimentation equilibrium ultracentrifugation.
      Surprisingly, the results indicated that interactions were strongly net
      attractive and electrostatics promoted self-association. Only repulsive
      interactions were expected based on prior work and calculations based a homology
      model of a related scFv crystal structure. However, the crystal structure lacks
      the charged, net-neutral linker sequence. PyRosetta was used to generate a set of
      scFv structures with different linker conformations, and coarse-grained Monte
      Carlo simulations were used to evaluate the effect of different linker
      configurations via second osmotic virial coefficient (B22 ) simulations. The
      results show that the configuration of the linker has a significant effect on the
      calculated B22 values, and can result in strong electrostatic attractions between
      oppositely charged residues on the protein surface. This is particularly relevant
      for development of non-natural antibody products, where charged linkers and other
      loop regions may be prevalent. The results also provide a preliminary
      computational framework to evaluate the effect of unstructured linkers on
      experimental protein-protein interaction parameters such as B22 .

PMID- 29637649
TI  - Histopathological lesions and toxicity in common carp (Cyprinus carpio L. 1758)
      induced by copper nanoparticles.
AB  - Different types of metal oxide nanoparticles (NPs) have been suggested for
      various applications such as water treatment and construction of agricultural
      pesticides; however, there are concerns about the potential toxicity of these
      compounds for the nontarget organism especially aquatic organisms. The aims of
      this study were assessing toxicity and histopathological effects of copper oxide
      NPs (NPs-CuO) on common carp (Cyprinus carpio) as a model organism. For this
      purpose 150 common carp with an average weight 7 +/- 1 g were exposed to 0, 10,
      20, 30, 40, 60, 80, 100, 150, and 200 mg/l of CuO-NPs (10 treatment with three
      replicates) for 96 hrs. After 24, 48, 72, and 96 hrs exposures, mortality rates
      recorded and gill samples were collected. Statistical analysis showed significant
      differences in carp survival between control and treatment groups (p < 0.05);
      regression between fish mortality rate and NPs-CuO concentration was also
      revealed (p < 0.01). The LC50 96h of NPs-CuO for common carp was estimated as
      124.9 mg/l in this study. Various tissue damages were observed in gill of
      treatments; such as, hypertrophy, hyperplasia, lamellar fusions, erythrocyte
      infiltration, epithelial lifting; also, there was significant correlation between
      intensity of tissue lesions and concentration of NPs-CuO (p < 0.01). The findings
      of the present study demonstrate that sublethal concentration of NPs-CuO can lead
      to serious tissue lesions. Whats more, concentrations above 30 ml/l of NPs-CuO
      can lead to some clinical signs; such as skin darkening and death with open mouth
      as well as definite fish death.

PMID- 29637650
TI  - A time-driven, activity-based costing methodology for determining the costs of
      red blood cell transfusion in patients with beta thalassaemia major.
AB  - OBJECTIVES: To describe the methodology to estimate the total cost of
      administration of a single unit of red blood cells (RBC) in adults with beta
      thalassaemia major in an Australian specialist haemoglobinopathy centre.
      BACKGROUND: Beta thalassaemia major is a genetic disorder of haemoglobin
      associated with multiple end-organ complications and typically requiring lifelong
      RBC transfusion therapy. New therapeutic agents are becoming available based on
      advances in understanding of the disorder and its consequences. Assessment of the
      true total cost of transfusion, incorporating both product and activity costs, is
      required in order to evaluate the benefits and costs of these new therapies.
      METHODS: We describe the bottom-up, time-driven, activity-based costing
      methodology used to develop process maps to provide a step-by-step outline of the
      entire transfusion pathway. Detailed flowcharts for each process are described.
      Direct observations and timing of the process maps document all activities,
      resources, staff, equipment and consumables in detail. The analysis will include
      costs associated with performing these processes, including resources and
      consumables. Sensitivity analyses will be performed to determine the impact of
      different staffing levels, timings and probabilities associated with performing
      different tasks. RESULTS: Thirty-one process maps have been developed, with over
      600 individual activities requiring multiple timings. These will be used for
      future detailed cost analyses. CONCLUSIONS: Detailed process maps using bottom
      up, time-driven, activity-based costing for determining the cost of RBC
      transfusion in thalassaemia major have been developed. These could be adapted for
      wider use to understand and compare the costs and complexities of transfusion in
      other settings.

PMID- 29637651
TI  - UPLC-Q-TOF-MS/MS-guided dereplication of Pulsatilla chinensis to identify
      triterpenoid saponins.
AB  - INTRODUCTION: Triterpenoid saponins are the major bioactive constituents of
      Pulsatilla chinensis, playing an important role in various biological activities
      such as anti-tumour, cognition-enhancing, anti-biosis, anti-inflammatory,
      hypoglycemic and immunological adjuvant. OBJECTIVE: To establish a systematic
      strategy based on ultra-high-performance liquid chromatography-quadrupole time-of
      flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) for the efficient
      characterisation and identification of triterpenoid saponins in crude extracts
      from Pulsatilla chinensis. METHODOLOGY: In this work, the strategy includes two
      aspects: (1) positive mode: by target screening, we can deduce the aglycone type
      and the composition of sugar moiety according to the fragment ions; untargeted
      screening includes four steps, find unknown, formula finder, ChemSpider search
      and MS/MS identification; (2) negative mode: according to the MS/MS spectra, the
      composition of sugar chain bonded to C-28 is inferred reasonably. The extract of
      Pulsatilla chinensis was separated within 60 min on a C18 column and eluted with
      methanol and water both containing 0.1% formic acid. RESULTS: As a result, a
      total of 22 triterpenoid saponins (11 pairs of isomers) with four aglycone
      skeletons were tentatively identified or elucidated in crude extracts from
      Pulsatilla chinensis based on their retention times, the mass spectrometric
      fragmentation patterns, and MS and MS/MS data. CONCLUSION: This study provides an
      efficient analysis strategy to rapidly identify the triterpenoid saponins in
      Pulsatilla species even in traditional Chinese medicines.

PMID- 29637652
TI  - Endoscopic Sinonasal Dissection Guide Roy R. Casiano Thieme Medical Publishers,
      New York, NY, 2012, USD $64.07, 128 pages.

PMID- 29637653
TI  - Mutation update for the GPC3 gene involved in Simpson-Golabi-Behmel syndrome and
      review of the literature.
AB  - Simpson-Golabi-Behmel syndrome (SGBS) is an X-linked multiple congenital
      anomalies and overgrowth syndrome caused by a defect in the glypican-3 gene
      (GPC3). Until now, GPC3 mutations have been reported in isolated cases or small
      series and the global genotypic spectrum of these mutations has never been
      delineated. In this study, we review the 57 previously described GPC3 mutations
      and significantly expand this mutational spectrum with the description of 29
      novel mutations. Compiling our data and those of the literature, we provide an
      overview of 86 distinct GPC3 mutations identified in 120 unrelated families,
      ranging from single nucleotide variations to complex genomic rearrangements and
      dispersed throughout the entire coding region of GPC3. The vast majority of them
      are deletions or truncating mutations (frameshift, nonsense mutations) predicted
      to result in a loss-of-function. Missense mutations are rare and the two which
      were functionally characterized, impaired GPC3 function by preventing GPC3
      cleavage and cell surface addressing respectively. This report by describing for
      the first time the wide mutational spectrum of GPC3 could help clinicians and
      geneticists in interpreting GPC3 variants identified incidentally by high
      throughput sequencing technologies and also reinforces the need for functional
      validation of non-truncating mutations (missense, in frame mutations,
      duplications).

PMID- 29637654
TI  - Exercise decreases defensive responses to unpredictable, but not predictable,
      threat.
AB  - BACKGROUND: Research supports the anxiolytic effect of exercise, but the
      mechanism underlying this effect is unclear. This study examines the influence of
      exercise in healthy controls on two distinct defensive states implicated in
      anxiety disorders: fear, a phasic response to a predictable threat, and anxiety,
      a sustained response to an unpredictable threat. METHODS: Thirty-four healthy
      volunteers (17 male, age M = 26.18, SD = 5.6) participated in sessions of
      exercise (biking at 60-70% of heart rate reserve) and control (biking at 10-20%
      of heart rate reserve) activity for 30 min, separated by 1 week. Threat responses
      were measured by eyeblink startle and assessed with the "Neutral-Predictable
      Unpredictable threat test," which includes a neutral (N) and two threat
      conditions, one with predictable (P) and one with unpredictable (U) shock.
      RESULTS: Results show that exercise versus control activity reduces startle
      potentiation during unpredictable threat (P = .031), but has no effect on startle
      potentiation during predictable threat (P = .609). CONCLUSIONS: These results
      suggest that exercise reduces defensive response to unpredictable, but not
      predictable, threat, a dissociation that may help inform clinical indications for
      this behavioral intervention, as well as provide clues to its underlying
      neurobehavioral mechanisms.

PMID- 29637655
TI  - A long-term experience with expansion of Milan criteria for liver transplant
      recipients.
AB  - The Milan criteria (MC) have historically determined eligibility for
      transplantation for hepatocellular carcinoma (HCC). The United Network for Organ
      Sharing (UNOS) Region 4 expanded the criteria for transplantation in HCC to
      include a single tumor <=6 cm or up to 3 tumors with the largest diameter <=5 cm
      and total additive diameter <=9 cm (R4C). The aim of this study was to report the
      10-year outcomes of this expanded criteria compared to MC. Transplants performed
      for HCC in Region 4 between October 2007 and December 2016 were reviewed using
      the UNOS database. Recipients were categorized based on imaging findings at
      initial evaluation. A total of 2068 patients were included in the study. There
      was no significant difference in 10-year patient survival between the groups (53%
      MC vs 48% R4C, P = .23). There was also no significant difference in recurrence
      free survival (54% MC vs 47% R4C, P = .15) or allograft survival (53% MC vs 48%
      R4C, P = .16). Finally, there was no significant difference in outcomes between
      the MC and R4C groups when stratifying patients by locoregional therapy. This
      study demonstrates promising data that the criteria for liver transplantation in
      HCC can be safely expanded to the R4C without compromising outcomes.

PMID- 29637656
TI  - Impaired neuroplasticity in the prefrontal cortex in depression indexed through
      paired associative stimulation.
AB  - BACKGROUND: Dysfunctional neuroplasticity may be one of the pathophysiological
      mechanisms underlying major depression. We have previously established methods to
      assess neuroplasticity from the dorsolateral prefrontal cortex (DLPFC) using a
      paired associative stimulation (PAS) paradigm, which pairs a preceding peripheral
      nerve stimulation with subsequent transcranial magnetic stimulation (TMS)
      combined with electroencephalography (EEG). We aimed to investigate
      neuroplasticity through the PAS paradigm in the DLPFC in patients with depression
      compared to healthy subjects. METHODS: Twenty-nine patients with depression and
      28 healthy controls participated in this study. There were no significant age or
      sex differences between the two groups. All participants received PAS paradigm in
      the DLPFC. We analyzed PAS induced potentiation from the DLPFC in both groups
      calculating the power of TMS-evoked potentials (TEP). A two-way ANOVA with PAS
      effect as a within-subject factor and diagnostic group as a between-subject
      factor was performed to examine the group differences in the PAS paradigm.
      RESULTS: DLPFC-PAS induced a significant potentiation at the stimulation site in
      both patients and healthy subjects (mean +/- SD: 1.24 +/- 0.33 [MUV] vs. 1.48 +/-
      0.28 [MUV]). However, when we compared PAS potentiation between patients and
      healthy subjects, there were significant main effects of PAS (F1,53  = 68.63, p <
      0.0001) and PAS-by-diagnostic group interaction (F1,53  = 25.05, p < 0.0001).
      Post hoc analysis demonstrated that patients had a significantly lower PAS
      potentiation compared to healthy subjects (t55  = 3.128, p = 0.003).
      CONCLUSTIONS: Our findings provide evidence for impaired neuroplasticity in DLPFC
      in patients with depression compared to healthy subjects. Such findings may
      ultimately help us understand the pathophysiology of MDD and mechanisms involved
      in its treatment.

PMID- 29637657
TI  - The response strategy and the place strategy in a plus-maze have different
      sensitivities to devaluation of expected outcome.
AB  - Previous studies have suggested that spatial navigation can be achieved with at
      least two distinct learning processes, involving either cognitive map-like
      representations of the local environment, referred to as the "place strategy", or
      simple stimulus-response (S-R) associations, the "response strategy". A similar
      distinction between cognitive/behavioral processes has been made in the context
      of non-spatial, instrumental conditioning, with the definition of two processes
      concerning the sensitivity of a given behavior to the expected value of its
      outcome as well as to the response-outcome contingency ("goal-directed action"
      and "S-R habit"). Here we investigated whether these two versions of dichotomist
      definitions of learned behavior, one spatial and the other non-spatial,
      correspond to each other in a formal way. Specifically, we assessed the goal
      directed nature of two navigational strategies, using a combination of an outcome
      devaluation procedure and a spatial probe trial frequently used to dissociate the
      two navigational strategies. In Experiment 1, rats trained in a dual-solution T
      maze task were subjected to an extinction probe trial from the opposite start
      arm, with or without prefeeding-induced devaluation of the expected outcome. We
      found that a non-significant preference for the place strategy in the non
      devalued condition was completely reversed after devaluation, such that
      significantly more animals displayed the use of the response strategy. The result
      suggests that the place strategy is sensitive to the expected value of the
      outcome, while the response strategy is not. In Experiment 2, rats with
      hippocampal lesions showed significant reliance on the response strategy,
      regardless of whether the expected outcome was devalued or not. The result thus
      offers further evidence that the response strategy conforms to the definition of
      an outcome-insensitive, habitual form of instrumental behavior. These results
      together attest a formal correspondence between two types of dual-process
      accounts of animal learning and behavior.

PMID- 29637659
TI  - Issue Information-Declaration of Helsinki.

PMID- 29637658
TI  - How Can We Improve Osteoporosis Care? A Systematic Review and Meta-Analysis of
      the Efficacy of Quality Improvement Strategies for Osteoporosis.
AB  - Although osteoporosis affects 10 million people in the United States, screening
      and treatment rates remain low. We performed a systematic review and meta
      analysis of the efficacy of quality improvement strategies to improve
      osteoporosis screening (bone mineral density [BMD]/dual-energy X-ray
      absorptiometry [DXA] testing) and/or treatment (pharmacotherapy) initiation
      rates. We developed broad literature search strategies for PubMed, Embase, and
      Cochrane Library databases, and applied inclusion/exclusion criteria to select
      relevant studies. Random-effects meta-analyses were performed for outcomes of
      BMD/DXA testing and/or osteoporosis treatment. Forty-three randomized clinical
      studies met inclusion criteria. For increasing BMD/DXA testing in patients with
      recent or prior fracture, meta-analyses demonstrated several efficacious
      strategies, including orthopedic surgeon or fracture clinic initiation of
      osteoporosis evaluation or management (risk difference 44%, 95% confidence
      interval [CI] 26%-63%), fracture liaison service/case management (risk difference
      43%, 95% CI 23%-64%), multifaceted interventions targeting providers and patients
      (risk difference 24%, 95% CI 15%-32%), and patient education and/or activation
      (risk difference 16%, 95% CI 6%-26%). For increasing osteoporosis treatment in
      patients with recent or prior fracture, meta-analyses demonstrated significant
      efficacy for interventions of fracture liaison service/case management (risk
      difference 20%, 95% CI 1%-40%) and multifaceted interventions targeting providers
      and patients (risk difference 12%, 95% CI 6%-17%). The only quality improvement
      strategy for which meta-analysis findings demonstrated significant improvement of
      osteoporosis care for patient populations including individuals without prior
      fracture was patient self-scheduling of DXA plus education, for increasing the
      outcome of BMD testing (risk difference 13%, 95% CI 7%-18%). The meta-analyses
      findings were limited by small number of studies in each analysis; high between
      study heterogeneity; sensitivity to removal of individual studies; and unclear
      risk of bias of included studies. Despite the limitations of the current body of
      evidence, our findings indicate there are several strategies that appear
      worthwhile to enact to try to improve osteoporosis screening and/or treatment
      rates. (c) 2018 American Society for Bone and Mineral Research.

PMID- 29637660
TI  - Ethnic Group Differences in Bullying Perpetration: A Meta-Analysis.
AB  - We examined ethnic differences in bullying perpetration in order to assess
      whether ethnic group membership was associated with higher involvement among (1)
      nonimmigrant and immigrant youth; and (2) White and visible minority youth (i.e.,
      Black, Hispanic, Asian, Indigenous, and Biracial). Fifty-three studies (N =
      740,176; 6-18-year-olds) were included in the meta-analysis. Results yielded very
      small and nonsignificant effect size differences across all group comparisons.
      Methodological moderator analyses indicated several differences across groups.
      Our findings provide initial support that the assessment of ethnicity as a
      descriptive variable is not sufficient to account for group differences in
      bullying perpetration.

PMID- 29637662
TI  - Early salivary changes in multiple myeloma patients undergoing autologous HSCT.
AB  - OBJECTIVE: One explorative observational study in two parts was performed to
      examine early salivary changes in relation to oral mucositis (OM) in multiple
      myeloma patients treated with high-dose melphalan and autologous haematopoietic
      stem cell transplantation (HSCT). As cryotherapy was introduced after part A as
      regular care, its effect on OM could be evaluated. METHODS: Unstimulated whole
      mouth saliva (UWS) and stimulated whole-mouth saliva (SWS) were collected, and OM
      was scored with the Oral Mucositis Nursing Instrument (OMNI) at days -3, 0, 4, 7,
      11 and 14 after HSCT. Salivary flow rate, total protein (BCA), mucin 5B, albumin
      (western blot), total IgA, lactoferrin and myeloperoxidase levels (ELISA) were
      determined. RESULTS: Trends of decreasing UWS and SWS flow rates and total IgA
      levels were observed. At days 7 and 11, increases in lactoferrin and albumin
      levels were found in UWS and SWS. A positive correlation was found between OMNI
      scores and albumin and lactoferrin levels in SWS (R2  = .56, p = .029 and R2  =
      .49, p = .043, respectively). In part B, cryotherapy significantly lowered peak
      OMNI scores. CONCLUSION: Compositional changes in saliva reflecting inflammation
      were found in the first days after HSCT, and the use of cryotherapy in the second
      part was associated with decreased OM severity.

PMID- 29637661
TI  - Cognitive performance in antidepressant-free recurrent major depressive disorder.
AB  - BACKGROUND: Cognitive complaints are common in depression, and cognition may be
      an important treatment target as cognitive problems often remain during remission
      and may contribute to recurrence risk. Previous studies of cognitive performance
      in depression have mainly examined late-life depression, with a focus on older
      adults, or assessed performance in specific cognitive tasks rather than cognitive
      domains. METHODS: This study examined cognitive performance across multiple
      cognitive domains in antidepressant-free depressed adults with early onset
      recurrent depression compared to never-depressed controls. Domain scores were
      calculated for episodic memory, executive function, processing speed, and working
      memory, and the effect of depression diagnosis, depression severity, and
      depression duration on each domain score was examined, including interactions
      with age, sex, and education. RESULTS: Currently depressed adults (n = 91)
      exhibited poorer performance in the processing speed domain compared with never
      depressed adults (n = 105). Additionally, there was an interactive effect of
      depression duration and age on processing speed and executive function domain
      performance, such that performance was worse with older age and longer duration
      of depression. There were no effects of depression severity on performance across
      the cognitive domains. CONCLUSIONS: These findings support that processing speed
      deficits appear in young adults with early onset depression that may not be
      related to current mood. Additionally, the effects of cumulative depressive
      episodes may interact with aging such that cognitive performance deficits worsen
      with recurrence over the lifespan.

PMID- 29637663
TI  - Digital phenotyping of suicidal thoughts.
AB  - BACKGROUND: To examine whether there are subtypes of suicidal thinking using real
      time digital monitoring, which allows for the measurement of such thoughts with
      greater temporal granularity than ever before possible. METHODS: We used
      smartphone-based real-time monitoring to assess suicidal thoughts four times per
      day in two samples: Adults who attempted suicide in the past year recruited from
      online forums (n = 51 participants with a total of 2,889 responses, surveyed over
      28 days; ages ranged from 18 to 38 years) and psychiatric inpatients with recent
      suicidal ideation or attempts (n = 32 participants with a total of 640 responses,
      surveyed over the duration of inpatient treatment [mean stay = 8.79 days], ages
      ranged 23-68 years). Latent profile analyses were used to identify distinct
      phenotypes of suicidal thinking based on the frequency, intensity, and
      variability of such thoughts. RESULTS: Across both samples, five distinct
      phenotypes of suicidal thinking emerged that differed primarily on the intensity
      and variability of suicidal thoughts. Participants whose profile was
      characterized by more severe, persistent suicidal thoughts (i.e., higher mean and
      lower variability around the mean) were most likely to have made a recent suicide
      attempt. CONCLUSIONS: Suicidal thinking has historically been studied as a
      homogeneous construct, but using newly available monitoring technology we
      discovered five profiles of suicidal thinking. Key questions for future research
      include how these phenotypes prospectively relate to future suicidal behaviors,
      and whether they represent remain stable or trait-like over longer periods.

PMID- 29637664
TI  - Intra- and interobserver agreement for fetal cerebral measurements in 3D
      ultrasonography.
AB  - The aim of this study is to evaluate intra- and interobserver agreement for
      measurement of intracranial, cerebellar, and thalamic volume with the Virtual
      Organ Computer-aided AnaLysis (VOCAL) technique in three-dimensional ultrasound
      images, in comparison to two-dimensional measurements of these brain structures.
      Three-dimensional ultrasound images of the brains of 80 fetuses at 20-24 weeks'
      gestational age were obtained from YOUth, a Dutch prospective cohort study. Two
      observers performed offline measurement of the occipitofrontal diameter,
      intracranial volume, transcerebellar diameter, cerebellar volume, and thalamic
      width, area, and volume, independently. VOCAL was used for calculation of the
      volumes. The two-way random, single measures intraclass correlation coefficient
      (ICC) was used for analysis of agreement and Bland-Altman plots were configured.
      Intra- and interobserver agreement was almost perfect for occipitofrontal
      diameter (intra ICC 0.88, 95% CI 0.82-0.92; inter ICC 0.91, 95% CI 0.85-0.94),
      intracranial volume (intra ICC 0.96, 95% CI 0.91-0.98; inter ICC 0.97, 95% CI
      0.96-0.98) and transcerebellar diameter (intra ICC 0.91, 95% CI 0.86-0.94; inter
      ICC 0.86, 95% CI 0.78-0.910). For cerebellar volume, the intraobserver agreement
      was almost perfect (0.85, 95% CI 0.76-0.90), whereas the interobserver agreement
      was substantial (0.75, 95% CI 0.44-0.88). Agreement was only moderate for
      thalamic measurements. Bland-Altman plots for the volume measurements are
      normally distributed with acceptable mean differences and 95% limits of
      agreement. The intra- and interobserver agreement of the measurement of
      intracranial and cerebellar volume with VOCAL was almost perfect. These
      measurements are therefore reliable, and can be used to investigate fetal brain
      development. Thalamic measurements are not reliable enough.

PMID- 29637665
TI  - Evaluating dimensional models of psychopathology in outpatients diagnosed with
      emotional disorders: A cautionary tale.
AB  - BACKGROUND: Mental disorders cluster together systematically. Through factor
      analysis of disorder comorbidity, investigators are establishing the latent
      dimensions that underlie the development of related syndromes. However, these
      dimensions have not been validated across diverse patient samples, in which
      comorbidity patterns vary widely. METHOD: We assessed 4,928 outpatients seeking
      treatment for emotional disorders with a semistructured diagnostic interview.
      This was the largest patient sample as yet for an evaluation of the latent
      structure of mental disorders. We compared several competing dimensional models
      of common mental disorders via confirmatory factor analysis. RESULTS: The
      hypothesized confirmatory factor model-anchored by internalizing and
      externalizing spectra-fit the diagnostic data poorly. Neither a one-factor model,
      reflecting a unitary liability to all mental disorders, nor a three-factor model,
      wherein the internalizing dimension bifurcated into distress and fear subfactors,
      fit appreciably better. CONCLUSIONS: These data provide novel evidence that the
      internalizing and externalizing spectra are not structurally sound in all
      clinical contexts. We speculate about the causes of model misfit and advise
      additional research into the generalizability-with respect to sample, input data,
      developmental stage, and more-of dimensional models of mental disorder.

PMID- 29637666
TI  - Rouleaux red blood cells splitting in microscopic thin blood smear images via
      local maxima, circles drawing, and mapping with original RBCs.
AB  - Splitting the rouleaux RBCs from single RBCs and its further subdivision is a
      challenging area in computer-assisted diagnosis of blood. This phenomenon is
      applied in complete blood count, anemia, leukemia, and malaria tests. Several
      automated techniques are reported in the state of art for this task but face
      either under or over splitting problems. The current research presents a novel
      approach to split Rouleaux red blood cells (chains of RBCs) precisely, which are
      frequently observed in the thin blood smear images. Accordingly, this research
      address the rouleaux splitting problem in a realistic, efficient and automated
      way by considering the distance transform and local maxima of the rouleaux RBCs.
      Rouleaux RBCs are splitted by taking their local maxima as the centres to draw
      circles by mid-point circle algorithm. The resulting circles are further mapped
      with single RBC in Rouleaux to preserve its original shape. The results of the
      proposed approach on standard data set are presented and analyzed statistically
      by achieving an average recall of 0.059, an average precision of 0.067 and F
      measure 0.063 are achieved through ground truth with visual inspection.

PMID- 29637668
TI  - Photocatalytic CO2 Reduction on TiO2 -Based Materials under Controlled Reaction
      Conditions: Systematic Insights from a Literature Study.
AB  - Photocatalytic CO2 conversion to hydrocarbons (sometimes referred to as
      'artificial photosynthesis'), which mimics natural photosynthesis with purely
      inorganic photocatalysts, has the potential to simultaneously combat the energy
      crisis and the greenhouse effect. In more than half of all reported studies to
      date, TiO2 -based materials are used as the photocatalyst. Yet, the reaction
      conditions and reactor designs employed in previous studies cover a vast range,
      hindering mutual comparisons of observed activities and selectivity. In this
      work, a systematic literature study is attempted, including a selection of only
      such research publications which report experimental conditions of high purity
      and a proof of the carbon source (blank experiments, 13 CO2 isotope labelling or
      stoichiometric O2 identification) for CO2 photoreduction. General trends were
      then detected and discussed, aiming to guide future research to more efficient
      photocatalytic systems.

PMID- 29637667
TI  - A longitudinal study of risk factors for suicide attempts among Operation
      Enduring Freedom and Operation Iraqi Freedom veterans.
AB  - BACKGROUND: Suicide rates among veterans have increased markedly since the onset
      of Operations Enduring Freedom (OEF) and Iraqi Freedom (OIF; LeardMann et al.,
      2013). Identification of factors with the greatest contribution to suicide risk
      among veterans is needed to inform risk assessment and to identify intervention
      targets. METHODS: This study examined predictors of suicide attempts among
      participants in the Veterans After-Discharge Longitudinal Registry; a nationwide
      cohort of OEF/OIF veterans enrolled in Department of Veterans Affairs (VA)
      services. Veterans with and without probable posttraumatic stress disorder (PTSD)
      were sampled at a 3:1 ratio, and male and female veterans were sampled at a 1:1
      ratio. Participants (N = 1,649) were assessed at two time points, roughly 2 years
      apart (M = 28.74 months, SD = 8.72). RESULTS: Seventy-four participants (4.49%)
      attempted suicide during the follow-up period. The strongest predictors of
      suicide attempts among the full sample were suicidal intent, attempt history,
      suicide ideation, PTSD symptoms, alcohol use disorder (AUD) symptoms, and
      depression. Veterans with multiple risk factors were particularly vulnerable; of
      veterans with 0, >=1, >=2, >=3, or >= 4 of these risk factors, 0%, 7.81%, 10.31%,
      18.45%, and 20.51% made a suicide attempt, respectively. CONCLUSIONS: This
      prospective study identified several strong predictors of suicide attempts among
      OEF/OIF veterans which may be important targets for suicide prevention efforts.
      Further, co-occurrence of multiple risk factors was associated with markedly
      greater risk for suicide attempts; veterans with multiple risk factors appear to
      be at the highest risk among OEF/OIF veterans enrolled in VA care.

PMID- 29637669
TI  - The World Health Organization 1973 classification system for grade is an
      important prognosticator in T1 non-muscle-invasive bladder cancer.
AB  - OBJECTIVES: To compare the prognostic value of the World Health Organization
      (WHO) 1973 and 2004 classification systems for grade in T1 bladder cancer (T1
      BC), as both are currently recommended in international guidelines. PATIENTS AND
      METHODS: Three uro-pathologists re-revised slides of 601 primary (first
      diagnosis) T1-BCs, initially managed conservatively (bacille Calmette-Guerin) in
      four hospitals. Grade was defined according to WHO1973 (Grade 1-3) and WHO2004
      (low-grade [LG] and high-grade [HG]). This resulted in a lack of Grade 1 tumours,
      188 (31%) Grade 2, and 413 (69%) Grade 3 tumours. There were 47 LG (8%) vs 554
      (92%) HG tumours. We determined the prognostic value for progression-free
      survival (PFS) and cancer-specific survival (CSS) in Cox-regression models and
      corrected for age, sex, multiplicity, size and concomitant carcinoma in situ.
      RESULTS: At a median follow-up of 5.9 years, 148 patients showed progression and
      94 died from BC. The WHO1973 Grade 3 was negatively associated with PFS (hazard
      ratio [HR] 2.1) and CSS (HR 3.4), whilst WHO2004 grade was not prognostic. On
      multivariable analysis, WHO1973 grade was the only prognostic factor for
      progression (HR 2.0). Grade 3 tumours (HR 3.0), older age (HR 1.03) and tumour
      size >3 cm (HR 1.8) were all independently associated with worse CSS. CONCLUSION:
      The WHO1973 classification system for grade has strong prognostic value in T1-BC,
      compared to the WHO2004 system. Our present results suggest that WHO1973 grade
      cannot be replaced by the WHO2004 classification in non-muscle-invasive BC
      guidelines.

PMID- 29637670
TI  - Monoamine Oxidase Deficiency Causes Prostate Atrophy and Reduces Prostate
      Progenitor Cell Activity.
AB  - Monoamine oxidases (MAOs) degrade a number of biogenic and dietary amines,
      including monoamine neurotransmitters, and play an essential role in many
      biological processes. Neurotransmitters and related neural events have been shown
      to participate in the development, differentiation, and maintenance of diverse
      tissues and organs by regulating the specialized cellular function and
      morphological structures of innervated organs such as the prostate. Here we show
      that mice lacking both MAO isoforms, MAOA and MAOB, exhibit smaller prostate mass
      and develop epithelial atrophy in the ventral and dorsolateral prostates. The
      cellular composition of prostate epithelium showed reduced CK5+ or p63+ basal
      cells, accompanied by lower Sca-1 expression in p63+ basal cells, but intact
      differentiated CK8+ luminal cells in MAOA/B-deficient mouse prostates. MAOA/B
      ablation also decreased epithelial cell proliferation without affecting cell
      apoptosis in mouse prostates. Using a human prostate epithelial cell line, we
      found that stable knockdown of MAOA and MAOB impaired the capacity of prostate
      stem cells to form spheres, coinciding with a reduced CD133+ /CD44+ /CD24- stem
      cell population and less expression of CK5 and select stem cell markers,
      including ALDH1A1, TROP2, and CD166. Alternative pharmacological inhibition of
      MAOs also repressed prostate cell stemness. In addition, we found elevated
      expression of MAOA and MAOB in epithelial and/or stromal components of human
      prostate hyperplasia samples compared with normal prostate tissues. Taken
      together, our findings reveal critical roles for MAOs in the regulation of
      prostate basal progenitor cells and prostate maintenance. Stem Cells 2018;36:1249
      1258.

PMID- 29637671
TI  - Near-Infrared Sensitized Photoinduced Atom-Transfer Radical Polymerization (ATRP)
      with a Copper(II) Catalyst Concentration in the ppm Range.
AB  - NIR-sensitized photoinduced atom-transfer radical polymerization (ATRP) is
      possible by using ppm of CuII /tris(2-pyridylmethyl)amine (TPMA) as the catalyst,
      a polymethine as the photosensitizer, and alpha-bromophenylacetate as the alkyl
      halide initiator. Among the polymethines investigated with cationic,
      zwitterionic, or anionic structures, only the zwitterionic 2 exhibited
      sensitization activity under NIR light at room temperature resulting in the
      formation of polymers with controlled molecular weight characteristics and
      functionalities. The barbital group placed at the meso-position of 2 caused the
      activity in this photo-ATRP framework. The chain-end fidelity of the polymers was
      confirmed by chain extension and block copolymerization experiments. The
      polymerization system exhibits high photostability under NIR light exposure and
      irradiation dependency as demonstrated by light on/off experiments.

PMID- 29637672
TI  - Triggered intravoxel incoherent motion MRI for the assessment of calf muscle
      perfusion during isometric intermittent exercise.
AB  - The main aim of this paper was to propose triggered intravoxel incoherent motion
      (IVIM) imaging sequences for the evaluation of perfusion changes in calf muscles
      before, during and after isometric intermittent exercise. Twelve healthy
      volunteers were involved in the study. The subjects were asked to perform
      intermittent isometric plantar flexions inside the MRI bore. MRI of the calf
      muscles was performed on a 3.0 T scanner and diffusion-weighted (DW) images were
      obtained using eight different b values (0 to 500 s/mm2 ). Acquisitions were
      performed at rest, during exercise and in the subsequent recovery phase. A motion
      triggered echo-planar imaging DW sequence was implemented to avoid movement
      artifacts. Image quality was evaluated using the average edge strength (AES) as a
      quantitative metric to assess the motion artifact effect. IVIM parameters
      (diffusion D, perfusion fraction f and pseudo-diffusion D*) were estimated using
      a segmented fitting approach and evaluated in gastrocnemius and soleus muscles.
      No differences were observed in quality of IVIM images between resting state and
      triggered exercise, whereas the non-triggered images acquired during exercise had
      a significantly lower value of AES (reduction of more than 20%). The isometric
      intermittent plantar-flexion exercise induced an increase of all IVIM parameters
      (D by 10%; f by 90%; D* by 124%; fD* by 260%), in agreement with the increased
      muscle perfusion occurring during exercise. Finally, IVIM parameters reverted to
      the resting values within 3 min during the recovery phase. In conclusion, the
      IVIM approach, if properly adapted using motion-triggered sequences, seems to be
      a promising method to investigate muscle perfusion during isometric exercise.

PMID- 29637673
TI  - Reconstruction of Supported Metal Nanoparticles in Reaction Conditions.
AB  - Metal nanoparticles (NPs) dispersed on a high-surface-area support are normally
      used as heterogeneous catalysts. Recent in situ experiments have shown that
      structure reconstruction of the NP occurs in real catalysis. However, the role
      played by supports in these processes is still unclear. Supports can be very
      important in real catalysis because of the new active sites at the perimeter
      interface between nanoparticles and supports. Herein, using a developed
      multiscale model coupled with in situ spherical aberration-corrected (Cs
      corrected) TEM experiments, we show that the interaction between the support and
      the gas environment greatly changes the contact surface area between the metal
      and support, which further leads to the critical change in the perimeter
      interface. The dynamic changes of the interface in reactive environments can thus
      be predicted and be included in the rational design of supported metal
      nanocatalysts. In particular, our multiscale model shows quantitative consistency
      with experimental observations. This work offers possibilities for obtaining
      atomic-scale structures and insights beyond the experimental limits.

PMID- 29637674
TI  - Psychosocial predictors of medication non-adherence in pediatric organ
      transplantation: A systematic review.
AB  - Adherence to immunosuppressant medication is critical to health and quality-of
      life outcomes for children who have received a solid organ transplant. Research
      on the psychological and social predictors of medication adherence is essential
      to the advancement of pretransplant assessments and transplant psychosocial
      services. Despite the importance of identifying risk factors, the literature
      remains limited regarding psychosocial predictors of non-adherence. A systematic
      search was conducted to identify studies of the psychosocial predictors of post
      transplant medication non-adherence in pediatric solid organ transplantation.
      From 1363 studies identified in searches of empirical literature, a final sample
      consisted of 54 publications representing 49 unique studies. Findings regarding
      psychosocial predictors were inconsistent with non-adherence associated largely
      with adolescence, racial/ethnic minority status, and presence of mental health
      issues. Familial predictors of non-adherence problems included single-parent
      households, lower socioeconomic status, lower family cohesion, presence of family
      conflict, and poor family communication. Several studies reported an association
      between non-adherence and social pressures (eg, peer social interaction, wanting
      to feel normal) among adolescent transplant recipients. While significant
      methodological and substantive gaps remain in this body of knowledge, this review
      synthesizes current evidence for assessment for transplant clinicians and
      researchers.

PMID- 29637675
TI  - Facile, Quick, and Gram-Scale Synthesis of Ultralong-Lifetime Room-Temperature
      Phosphorescent Carbon Dots by Microwave Irradiation.
AB  - Long-lifetime room-temperature phosphorescence (RTP) materials are important for
      many applications, but they are highly challenging materials owing to the spin
      forbidden nature of triplet exciton transitions. Herein, a facile, quick and gram
      scale method for the preparation of ultralong RTP (URTP) carbon dots (CDs) was
      developed via microwave-assisted heating of ethanolamine and phosphoric acid
      aqueous solution. The CDs exhibit the longest RTP lifetime, 1.46 s (more than 10
      s to naked eye) for CDs-based materials to date. The doping of N and P elements
      is critical for the URTP which is considered to be favored by a n->pi* transition
      facilitating intersystem crossing (ISC) for effectively populating triplet
      excitons. In addition, possibilities of formation of hydrogen bonds in the
      interior of the CDs may also play a significant role in producing RTP. Potential
      applications of the URTP CDs in the fields of anti-counterfeiting and information
      protection are proposed and demonstrated.

PMID- 29637676
TI  - Miniaturized Biosensors to Preserve and Monitor Cultural Heritage: from Medical
      to Conservation Diagnosis.
AB  - The point-of-care testing concept has been exploited to design and develop
      portable and cheap bioanalytical systems that can be used on-site by
      conservators. These systems employ lateral flow immunoassays to simultaneously
      detect two proteins (ovalbumin and collagen) in artworks. For an in-depth study
      on the application of these portable biosensors, both chemiluminescent and
      colorimetric detections were developed and compared in terms of sensitivity and
      feasibility. The chemiluminescent system displayed the best analytical
      performance (that is, two orders of magnitude lower limits of detection than the
      colorimetric system). To simplify its use, a disposable cartridge was designed ad
      hoc for this specific application. These results highlight the enormous potential
      of these inexpensive, easy-to-use, and minimally invasive diagnostic tools for
      conservators in the cultural heritage field.

PMID- 29637677
TI  - A Biomimetic Nickel Complex with a Reduced CO2 Ligand Generated by Formate
      Deprotonation and Its Behaviour towards CO2.
AB  - Reduced CO2 species are key intermediates in a variety of natural and synthetic
      processes. In the majority of systems, however, they elude isolation or
      characterisation owing to high reactivity or limited accessibility (heterogeneous
      systems), and their formulations thus often remain uncertain or are based on
      calculations only. We herein report on a Ni-CO22- complex that is unique in many
      ways. While its structural and electronic features help understand the CO2 -bound
      state in Ni,Fe carbon monoxide dehydrogenases, its reactivity sheds light on how
      CO2 can be converted into CO/CO32- by nickel complexes. In addition, the complex
      was generated by a rare example of formate beta-deprotonation, a mechanistic step
      relevant to the nickel-catalysed conversion of Hx COyz- at electrodes and formate
      oxidation in formate dehydrogenases.

PMID- 29637678
TI  - Reducing research waste through the standardisation of outcomes and definitions.

PMID- 29637679
TI  - Behavioral and psychosocial factors associated with suicidal ideation among
      adolescents.
AB  - Suicidal ideation poses a serious threat to the well-being of adolescents and is
      the strongest risk factor for suicide. Indeed, Korea ranks first among
      Organisation for Economic Cooperation and Development countries regarding the age
      standardized suicide rates. In the present study, we examined multiple levels of
      factors associated with the suicidal ideation of adolescents in Korea by applying
      the Ecological Models of Health Behavior. A cross-sectional study was conducted
      with a convenience sample of 860 adolescents. The instruments included the Beck
      Depression Inventory and the Adolescent Mental Health and Problem Behavior
      Questionnaire. The data were analyzed using hierarchical multiple regression.
      Sixteen percent of participants reported suicidal ideation. Intrapersonal (sleep
      disturbance, Internet game addiction, destructive behavior, and depressive
      symptoms) and interpersonal factors (family conflicts and peer victimization)
      were associated with suicidal ideation. Because multiple factors were associated
      with suicidal ideation among adolescents, both intrapersonal (sleep disturbance,
      Internet game addiction, and depression) and interpersonal factors (family
      conflicts and peer problems) should be considered in the development of suicide
      prevention programs. These programs could include campaigns changing the norms
      (permissive attitudes toward school violence) and the development of strict and
      rigorous school non-violence policies.

PMID- 29637680
TI  - Divergent Control of Point and Axial Stereogenicity: Catalytic Enantioselective C
      N Bond-Forming Cross-Coupling and Catalyst-Controlled Atroposelective
      Cyclodehydration.
AB  - Catalyst control over reactions that produce multiple stereoisomers is a
      challenge in synthesis. Control over reactions that involve stereogenic elements
      remote from one another is particularly uncommon. Additionally, catalytic
      reactions that address both stereogenic carbon centers and an element of axial
      chirality are also rare. Reported herein is a catalytic approach to each
      stereoisomer of a scaffold containing a stereogenic center remote from an axis of
      chirality. Newly developed peptidyl copper complexes catalyze an unprecedented
      remote desymmetrization involving enantioselective C-N bond-forming cross
      coupling. Then, chiral phosphoric acid catalysts set an axis of chirality through
      an unprecedented atroposelective cyclodehydration to form a heterocycle with high
      diastereoselectivity. The application of chiral copper complexes and phosphoric
      acids provides access to each stereoisomer of a framework with two different
      elements of stereogenicity.

PMID- 29637681
TI  - Bio-inspired Domino oxa-Michael/Diels-Alder/oxa-Michael Dimerization of para
      Quinols.
AB  - A bio-inspired, pyrrolidine-mediated, dimerization of para-quinols has been
      developed. It represents one of the most complex, yet general, dimerization
      reactions ever disclosed, selectively forming four new bonds, four new rings, and
      eight new contiguous stereogenic centres. The para-quinol starting materials are
      easily handled, bench-stable compounds, accessed in just one step from aromatic
      feedstocks. The reaction can be scaled up to give grams of polycyclic material,
      primed for further elaboration.

PMID- 29637683
TI  - Germ layers, the neural crest and emergent organization in development and
      evolution.
AB  - Discovered in chick embryos by Wilhelm His in 1868 and named the neural crest by
      Arthur Milnes Marshall in 1879, the neural crest cells that arise from the neural
      folds have since been shown to differentiate into almost two dozen vertebrate
      cell types and to have played major roles in the evolution of such vertebrate
      features as bone, jaws, teeth, visceral (pharyngeal) arches, and sense organs. I
      discuss the discovery that ectodermal neural crest gave rise to mesenchyme and
      the controversy generated by that finding; the germ layer theory maintained that
      only mesoderm could give rise to mesenchyme. A second topic of discussion is germ
      layers (including the neural crest) as emergent levels of organization in animal
      development and evolution that facilitated major developmental and evolutionary
      change. The third topic is gene networks, gene co-option, and the evolution of
      gene-signaling pathways as key to developmental and evolutionary transitions
      associated with the origin and evolution of the neural crest and neural crest
      cells.

PMID- 29637682
TI  - Chimeric 3' flanking regions strongly enhance gene expression in plants.
AB  - Plants represent a promising platform for the highly scalable production of
      recombinant proteins. Previously, we identified the tobacco extensin terminator
      lacking its intron as an element that reduced transcript read-through and
      improved recombinant protein production in a plant-based system. In this study,
      we systematically compared nonreplicating plant expression vectors containing
      over 20 commonly used or newly identified terminators from diverse sources. We
      found that eight gene terminators enhance reporter gene expression significantly
      more than the commonly used 35S and NOS terminators. The intronless extensin
      terminator provided a 13.6-fold increase compared with the NOS terminator.
      Combining terminators in tandem produced large synergistic effects, with many
      combinations providing a >25-fold increase in expression. Addition of the tobacco
      Rb7 or TM6 matrix attachment region (MAR) strongly enhanced protein production
      when added to most terminators, with the Rb7 MAR providing the greatest
      enhancement. Using deletion analysis, the full activity of the 1193 bp Rb7 MAR
      was found to require only a 463-bp region at its 3' end. Combined terminators and
      MAR together provided a >60-fold increase compared with the NOS terminator alone.
      These combinations were then placed in a replicating geminiviral vector,
      providing a total of >150-fold enhancement over the original NOS vector,
      corresponding to an estimated yield of 3-5 g recombinant protein per kg leaf
      fresh weight or around 50% of the leaf total soluble protein. These results
      demonstrate the importance of 3' flanking regions in optimizing gene expression
      and show great potential for 3' flanking regions to improve DNA-based recombinant
      protein production systems.

PMID- 29637684
TI  - Selective Monomethylation of Amines with Methanol as the C1 Source.
AB  - The N-monomethyl functionality is a common motif in a variety of synthetic and
      natural compounds. However, facile access to such compounds remains a fundamental
      challenge in organic synthesis owing to selectivity issues caused by
      overmethylation. To address this issue, we have developed a method for the
      selective, catalytic monomethylation of various structurally and functionally
      diverse amines, including typically problematic primary aliphatic amines, using
      methanol as the methylating agent, which is a sustainable chemical feedstock.
      Kinetic control of the aliphatic amine monomethylation was achieved by using a
      readily available ruthenium catalyst at an adequate temperature under hydrogen
      pressure. Various substrates including bio-related molecules and pharmaceuticals
      were selectively monomethylated, demonstrating the general utility of the
      developed method.

PMID- 29637685
TI  - Characteristic features of thermoluminescence in neodymium-doped gallium sulfide.
AB  - The thermoluminescence (TL) of neodymium-doped gallium sulfide (GaS:Nd) single
      crystals was measured from 10 K to room temperature with various heating rates
      between 0.2 and 1.0 K/sec. Two peaks centered at 70.9 K and 116.0 K were observed
      when using a heating rate of 0.8 K/sec. Initial rise and curve fitting methods
      were used to obtain information on trap activation energies. Activation energies
      of 94 and 216 meV were found for two analyzable peaks. The heating rate
      dependencies of TL intensities revealed that one of the observed peaks showed
      normal behavior according to the one trap-one recombination model, whereas the
      other model showed anomalous heating rate behavior. TL experiments were also
      carried out at different illumination temperatures from 10 to 32 K; maximum peak
      temperature remained almost the same at various illumination temperatures. This
      behavior indicated that the revealed trapping centers are single, discrete
      levels. The TL glow curves of undoped GaS crystals were also investigated and the
      effect of Nd doping on the TL characteristics of crystals is discussed in the
      manuscript.

PMID- 29637686
TI  - Nordihydroguaiaretic acid can suppress progression of experimental autoimmune
      encephalomyelitis.
AB  - Multiple sclerosis (MS) is a poorly understood disease mechanistically. MOG35-55
      peptide induced experimental autoimmune encephalomyelitis (EAE) is a broadly used
      model to study MS. Using this model we have earlier shown that the antioxidant
      tempol or the small molecule inhibitor of p38 SB203580 can effectively prevent
      EAE progression. This effect was mediated by means of regulating immune
      inflammation, signaling by the p38MAPK-SGK1 pathway, and oxidative stress.
      However, there is a need to test drugs that can be used in pharmacological
      intervention of EAE. Given that nordihydroguaiaretic Acid (NDGA) has been shown
      to possess anti-oxidant activity and capacity of antagonizing autoimmune
      inflammation, we tested the effect of NDGA in ameliorating EAE in the current
      study. NDGA showed significant beneficial effect against EAE with both anti
      inflammation and antioxidant activity. NDGA could weaken the immune inflammation
      at least partly by inhibiting the oxidant stress-p38MAPK-SGK1 pathway
      representing a target for putative pharmacological intervention. (c) 2018 IUBMB
      Life, 70(5):432-436, 2018.

PMID- 29637687
TI  - Pediatric Early Warning Systems aid in triage to intermediate versus intensive
      care for pediatric oncology patients in resource-limited hospitals.
AB  - Pediatric oncology patients hospitalized in resource-limited settings are at high
      risk for clinical deterioration resulting in mortality. Intermediate care units
      (IMCUs) provide a cost-effective alternative to pediatric intensive care units
      (PICUs). Inappropriate IMCU triage, however, can lead to poor outcomes and
      suboptimal resource utilization. In this study, we sought to characterize
      patients with clinical deterioration requiring unplanned transfer to the IMCU in
      a resource-limited pediatric oncology hospital. Patients requiring subsequent
      early PICU transfer had longer PICU length of stay. PEWS results prior to IMCU
      transfer were higher in patients requiring early PICU transfer, suggesting PEWS
      can aid in triage between IMCU and PICU care.

PMID- 29637688
TI  - Epidemiologic and clinical characteristics of nontransfusion-dependent
      thalassemia in the United States.
AB  - BACKGROUND: Nontransfusion-dependent thalassemia (NTDT) refers to a diverse group
      of thalassemia mutations and clinical phenotypes that do not require chronic
      transfusions. It is increasingly prevalent in the United States. PROCEDURE: This
      study reviews the epidemiology and clinical characteristics of 138 patients with
      NTDT treated at four US thalassemia centers from 1997 to 2014. Data on laboratory
      results, transfusions, and clinical complications were collected from patient
      charts. RESULTS: Overall, 84 patients with alpha-thalassemia (62 deletional
      hemoglobin H; 22 nondeletional hemoglobin H), 39 with beta-thalassemia (26 with
      homozygous or double heterozygous beta mutations; 13 with single beta mutations
      with or without alpha triplication), and 15 with E/beta-thalassemia (12 E/beta0 ;
      three E/beta+ ) were identified. At study entry, the median age for patients with
      alpha-thalassemia was 2.3 years; 9.2 years for patients with beta-thalassemia and
      2.2 years for patients with E/beta-thalassemia. Most patients with alpha
      thalassemia were Asian. Patients with beta-thalassemia were predominantly
      Caucasian (46%) or of African descent (36%). Twenty percent of patients were born
      outside the United States and 5% were transfused before immigration.
      Complications varied by genotype and age. Individuals with nondeletional
      hemoglobin H were severely affected and, despite their young age, had many
      complications. Iron overload increased with age and was more common in patients
      who received transfusions. CONCLUSIONS: NTDT in the United States is a multi
      ethnic disease with different genotypic mutations and phenotypic manifestations.
      A higher than expected proportion of patients was Black/African American. NTDT
      related complications are common and increase with age, supporting a need for
      early diagnosis.

PMID- 29637689
TI  - Efficacy of a clinical pathway for patients with thyroid cancer.
AB  - BACKGROUND: Clinical pathways have been proposed as a way to improve
      organizational efficiency and maximize patient outcomes. However, little is known
      as to whether a clinical pathway is effective for thyroid cancer. METHODS: The
      study subjects included 216 patients who were managed after clinical pathway
      implementation and 145 control patients. Length of stay, cost per patient, and
      nurses' satisfaction were compared in the 2 groups. RESULTS: Mean length of stay
      was 0.8 days shorter in the clinical pathway group than in the control group (2.9
      vs 3.7 days; P = .023). Cost per patient was also lower in the clinical pathway
      than in the control group (USD $3953.00 vs USD $4636.00; P < .001). Nurses'
      overall satisfaction scores improved from 71.6% before to 82.5% after
      implementation of the clinical pathway and their job characteristics scores
      increased from 61.1% to 75.0%. CONCLUSION: Implementation of a clinical pathway
      for thyroid cancer can improve nurses' satisfaction with reduction of hospital
      stay and costs.

PMID- 29637692
TI  - Eversion Bile Duct Anastomosis: A Safe Alternative for Bile Duct Size Discrepancy
      in Deceased Donor Liver Transplantation.
AB  - Bile duct size discrepancy in liver transplantation may increase the risk of
      biliary complications (BCs). The aim of this study was to evaluate the safety and
      outcomes of the eversion bile duct anastomosis technique in deceased donor liver
      transplantation (DDLT) with duct-to-duct anastomosis. A total of 210 patients who
      received a DDLT with duct-to-duct anastomosis from 2012 to 2017 were divided into
      2 groups: those who had eversion bile duct anastomosis (n = 70) and those who had
      standard bile duct anastomosis (n = 140). BC rates were compared between the 2
      groups. There was no difference in the cumulative incidence of biliary strictures
      (P = 0.20) and leaks (P = 0.17) between the 2 groups. The BC rate in the eversion
      group was 14.3% and 11.4% in the standard anastomosis group. All the BCs in the
      eversion group were managed with endoscopic stenting. A severe size mismatch
      (>=3:1 ratio) was associated with a significantly higher incidence of biliary
      strictures (44.4%) compared with a 2:1 ratio (8.2%; P = 0.002). In conclusion,
      the use of the eversion technique is a safe alternative for bile duct discrepancy
      in DDLT. However, severe bile duct size mismatch may be a risk factor for biliary
      strictures with such a technique.

PMID- 29637691
TI  - Aggregation-induced emission enhancement of anthracene-derived Schiff base
      compounds and their application as a sensor for bovine serum albumin and optical
      cell imaging.
AB  - Three anthracene-based Schiff base complexes, R1-R3 (R1 = (E)-N'-((anthracen-10
      yl)methylene)benzohydrazide; R2 = (E)-1-((anthracen-10-yl)methylene)-4
      phenylsemicarbazide; and R3 = (E)-1-((anthracen-10-yl)methylene)-4
      phenylthiosemicarbazide) were synthesized from 9-anthracenecarboxaldehyde,
      benzohydrazide, 4-phenylsemicarbazide and 4-phenylthiosemi-carbazide
      respectively, and characterized by various spectral techniques. The absorption
      spectral characteristics of R1-R3 were bathochromically tuned to the visible
      region by extending the pi conjugation. These target compounds were weakly
      fluorescent in tetrahydrofuran (THF) solution because of rapid isomerization of
      the C=N double bond in the excited state. However, the aqueous dispersion of R1
      R3 in the THF/water mixture by the gradual addition of water up to 90% resulted
      in an increase in the fluorescence intensity mainly due to aggregation-induced
      emission enhancement (AIEE) properties. The formation of nanoaggregates of R1-R3
      were confirmed by scanning electron microscopy (SEM) and atomic force microscopy
      (AFM) techniques. The compounds R1-R3 are ideal probes for the fluorescence
      sensing of bovine serum albumin (BSA) and breast cancer cells by optical cell
      imaging.

PMID- 29637693
TI  - Oral insulin does not alter gut microbiota composition of NOD mice.
AB  - BACKGROUND: Oral insulin as a preventive strategy and/or treatment of type 1
      diabetes has been the target of much research. Producing oral insulins is a
      complex and challenging task, with numerous pitfalls, due to physiological,
      physical, and biochemical barriers. Our aim was to determine the impact of oral
      insulin on the delicate gut microbiota composition. METHODS: Female nonobese
      diabetic mice were given oral porcine insulin 2 times a week from 5 weeks of age
      for 4 weeks, and then subsequently once a week for 21 weeks, or until euthanized.
      The mice were divided into groups on a gluten-reduced diet or a standard diet.
      Gut microbiota composition was analysed based on faecal samples, and the type 1
      diabetes incidence of the mice was monitored. RESULTS: We observed no influence
      of the oral porcine insulin on the gut microbiota composition of mice on a gluten
      reduced or a standard diet at 9 weeks of age. Also, the administration of oral
      insulin did not influence the incidence of type 1 diabetes at 30 weeks of age.
      CONCLUSIONS: Oral porcine insulin does not alter the gut microbiota composition
      of nonobese diabetic mice on either a gluten-reduced diet or standard diet. Also,
      the oral porcine insulin did not influence the incidence of type 1 diabetes in
      the groups.

PMID- 29637694
TI  - Soluble laminin polymers enhance axon growth of primary neurons in vitro.
AB  - A substrate of laminin polymers formed at pH 4 (acidic pH-induced laminin; aLam)
      promotes neurite growth of embryonic rat cortical neurons better than a substrate
      of similar but structurally different laminin polymers formed at neutral pH
      (neutral pH-induced laminin; nLam). We investigated the effects of these laminin
      polymers, used as soluble supplements, on neurite growth of cultured adult rat
      primary dorsal root ganglion neurons. When added to the culture medium, aLam was
      found to promote neurite growth about twofold better than nLam. Immunoblocking
      experiments revealed that aLam elicited neurite growth to a similar extent
      through the alpha1 or alpha3 integrin subunit, while nLam required the
      availability of the alpha1 integrin subunit to elicit neurite growth. With aLam,
      but not nLam, immunoblocking of the alpha1 or alpha3 subunit resulted in an
      increase in the protein level of the alternative subunit. The presence of a
      mature focal adhesion complex, which is associated with neurite growth, was
      elevated in neurons in the presence of aLam relative to nLam or culture medium.
      Our data indicated that the two types of laminin polymers promote neurite growth
      of adult rat primary sensory neurons to a different degree, likely through
      different ligand-receptor interactions. These findings support the potential of
      soluble laminin polymers as injectable therapeutics for eliciting axon growth
      after nervous system injury. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res
      Part A: 106A:2372-2381, 2018.

PMID- 29637695
TI  - Spectrofluorimetric determination of acotiamide hydrochloride trihydrate in the
      presence of its oxidative degradation product.
AB  - Acotiamide hydrochloride trihydrate is a novel gastroprokinetic drug which has
      been recently approved for the treatment of patients with functional dyspepsia.
      This study presents the first reported to investigate the fluorimetric behavior
      of acotiamide hydrochloride trihydrate in the presence of its oxidative
      degradation product. All variables that affect fluorescence intensity were
      studied and optimized. The described method involved the measurement of native
      fluorescence of the drug in ethanol at 404 nm after excitation at 326 nm.
      Calibration plot was found to be linear over the concentration range 0.1-0.9
      MUg/ml. The specificity of the method has been tested via selective determination
      of the studied drug in its synthetic mixtures with its degradation product. The
      proposed method has been successfully applied to the analysis of the drug in its
      new pharmaceutical dosage form and the results have been statistically compared
      with the reported HPLC method showing no significant differences by applying t
      test and F-test.

PMID- 29637696
TI  - In vitro degradation and in vivo toxicity of NanoMatrix3D(r) polycaprolactone and
      poly(lactic acid) nanofibrous scaffolds.
AB  - Nanofibrous materials present unique properties favorable in many biomedicine and
      industrial applications. In this research we evaluated biodegradation, tissue
      response and general toxicity of nanofibrous poly(lactic acid) (PLA) and
      polycaprolactone (PCL) scaffolds produced by conventional method of
      electrospinning and using NanoMatrix3D(r) (NM3D(r) ) technology. Mass density,
      scanning electron microscopy and in vitro degradation (static and dynamic) were
      used for material characterization, and subcutaneous, intramuscular and
      intraperitoneal implantation - for in vivo tests. Biochemical blood analysis and
      histology were used to assess toxicity and tissue response. Pore size and fiber
      diameter did not differ in conventional and NM3D(r) PLA and PCL materials, but
      mass density was significantly lower in NM3D(r) ones. Scaffolds made by
      conventional method showed toxic effect during the in-vivo tests due to residual
      concentration of chloroform that released with material degradation. NM3D(r)
      method allowed cleaning scaffolds from residual solutions that made them nontoxic
      and biocompatible. Subcutaneous, intramuscular and intraperitoneal implantation
      of PCL and PLA NM3D(r) electrospun nanofibrous scaffolds showed their appropriate
      cell conductive properties, tissue and vessels formation in all sites. Thus,
      NM3D(r) PCL and PLA nanofibrous electrospun scaffolds can be used in the field of
      tissue engineering, surgery, wound healing, drug delivery, and so forth, due to
      their unique properties, nontoxicity and biocompatibility. (c) 2018 Wiley
      Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2200-2212, 2018.

PMID- 29637698
TI  - Muscle biology after spinal cord injury: Recent advances and future challenges.

PMID- 29637697
TI  - Temporal trends of splenectomy in pediatric hospitalizations with immune
      thrombocytopenia.
AB  - BACKGROUND: Splenectomy is considered an effective treatment for immune
      thrombocytopenia (ITP) with 70-80% response rate. However, its current use is
      limited in children with ITP. It is unclear if the rates of splenectomy have
      changed over time. Using a large nationally representative database, we aimed to
      study the trends of splenectomy in pediatric hospitalizations with ITP, and the
      factors associated with splenectomy during these encounters. METHODS: Using
      National (Nationwide) Inpatient Sample (NIS), and international classification of
      diseases (9th revision), clinical modification (ICD-9-CM) codes, we studied
      pediatric ITP hospitalizations with occurrence of total splenectomy between 2005
      and 2014. RESULTS: Out of 37,844 weighted ITP hospitalizations from 2005 to 2014;
      total splenectomy was performed in 954 encounters. Splenectomy rate declined over
      time (3.4% [2005-2006] to 1.6% [2013-2014], P < 0.001) with the younger age (<=5
      years) having the most notable decline (0.91% [2005-2006] to 0.14% [2013-2014], P
      < 0.001). Splenectomy had higher odds of being performed electively than non
      electively (odds ratio [OR]: 19.34, 95% confidence interval [CI]: 12.06-31.02, P
      < 0.001). Encounters with intracranial bleed were associated with the occurrence
      of splenectomy (OR: 17.87, 95% CI: 5.07-62.97, P < 0.001). Intracranial bleed (P
      < 0.001), gastrointestinal bleed (P < 0.01), sepsis (P < 0.001), and thrombosis
      (P < 0.001) were associated with longer length of stay and higher cost of
      hospitalization. CONCLUSIONS: Overall, splenectomy rates consistently declined
      over time. Intracranial hemorrhage during hospitalizations with ITP was
      associated with occurrence of splenectomy. Future studies should continue to
      reevaluate the rates of splenectomy in pediatric ITP in the presence of various
      second-line pharmacologic agents.

PMID- 29637699
TI  - Novel quinazolin-4(3H)-one linked to 1,2,3-triazoles: Synthesis and anticancer
      activity.
AB  - In this work, a wide range of novel quinazolin-4(3H)-one linked to 1,2,3
      triazoles was designed, synthesized, and evaluated against a panel of three human
      breast (MDA-MB-231, MCF-7, T-47D), lung (A549), and prostate (PC3) cancer cell
      lines. Our results revealed that the anticancer activity of the synthesized
      compounds was selectively affected by the presence of methoxy group on the linker
      between quinazolinone and 1,2,3-triazole moieties. According to the calculated
      IC50 values, compounds 6q, 6w, and 6x showed good cytotoxicity against breast
      cancer cell lines even more effective than the reference drug, etoposide.
      Compounds 6q and 6u were found to be potent compounds against A549, non-small
      cell lung cancer (NSCLC), comparing with erlotinib. Also, the morphological
      analysis by acridine orange/ethidium bromide double staining test and flow
      cytometry analysis indicated that potent compounds induced apoptosis in human
      cancer cell lines. Molecular docking studies were performed to clarify the
      inhibition mode of compounds 6g, 6u, 6w, and 6x over the EGFR active site. The
      most promising compounds, 6q and 6u, possessing 3-methoxy group were well
      oriented to the gatekeeper hydrophobic pocket of EGFR active site and interact
      well with Ala719, Val702, and Leu820 through hydrophobic interaction.

PMID- 29637700
TI  - Efficacy and safety of administering pediatric treatment to adolescent patients
      with mature B-cell non-Hodgkin lymphoma within the Japanese Pediatric
      Leukemia/Lymphoma Study Group clinical trial.
AB  - BACKGROUND: Currently, there is no standardized treatment for adolescents, aged
      15 years or older, with mature B-cell non-Hodgkin lymphoma (B-NHL), although this
      age group has been reported to have a poorer prognosis than younger patients.
      PROCEDURE: The present study analyzed the data of 321 patients with B-NHL,
      enrolled in a pediatric clinical trial, comparing the treatment outcomes between
      adolescents (aged 15-18 years, n = 25) and children (<=15 years, n = 297), with a
      particular focus on the safety and tolerability of administering pediatric
      regimens to adolescents. RESULTS: The probability of event-free survival (EFS) at
      4 years was 79.3 +/- 8.3% for the adolescents and 88.0 +/- 1.9% for the children
      (P = 0.236). After adjusting for treatment group and lactate dehydrogenase value
      at the time of diagnosis, the probability of 4-year EFS of adolescents was lower
      than that of children, but only in the patients with central nervous system
      positive lymphoma or Burkitt leukemia. The frequency of treatment-related
      mortalities, severe adverse events (SAEs), and SAEs leading to treatment
      discontinuation or treatment completion rate was similar in adolescent and
      pediatric patients. There was no difference in treatment duration between
      adolescent and pediatric patients. CONCLUSIONS: The treatment outcomes of
      adolescents with B-NHL were not statistically different from those of the
      pediatric patients and the safety of a pediatric regimen in adolescents was
      similar to that in the pediatric patients. A pediatric treatment foundation can
      be adopted for adolescents, although further prospective studies and biological
      investigations are required for treatment optimization.

PMID- 29637701
TI  - DNA:RNA hybrids at telomeres - when it is better to be out of the (R) loop.
AB  - R-loops (RLs) are three-stranded nucleic acid structures that contain a DNA:RNA
      hybrid and a displaced DNA strand. Genomic regions with GC skew and a G-rich
      transcript are particularly prone to form RLs. RLs play important physiological
      roles in cells; however, when present at abnormally high levels, they may
      threaten genome stability. The perfect GC skew of telomeric repeats and the
      discovery of telomeric repeat-containing RNA (TERRA), a long noncoding transcript
      that consists of the G-rich telomeric sequence, make telomeric sequences the
      perfect candidates for generating RLs. Indeed, in the past 5 years, telomere R
      loops (TRLs) have been demonstrated in Saccharomyces cerevisiae, Trypanosoma
      brucei, and human cells. The presence of TRLs in normal human cells that
      transcribe low levels of TERRA, suggests a physiological role for these nucleic
      structures in telomere maintenance. Abnormally enhanced TERRA transcription, as
      found in several human pathological conditions, leads to high TRL levels and
      various cellular outcomes, depending on the recombinogenic capabilities of the
      cells. Study of TRLs in various organisms highlights the necessity for tight
      regulation of these structures, which can switch from beneficial to detrimental
      under different conditions. Here, we review the current state of knowledge on
      TRLs, describe several means by which TRLs are regulated, and discuss how
      findings from yeast are relevant to human pathological scenarios in which TRLs
      are deregulated.

PMID- 29637702
TI  - Development of an Efficient Dual-Action GST-Inhibiting Anticancer Platinum(IV)
      Prodrug.
AB  - The cytotoxicity of cisplatin (cDDP) is enhanced when co-administered with
      ethacrynic acid (EA), a glutathione S-transferase (GST) inhibitor. A PtIV -EA
      conjugate containing a cDDP core and two axial ethacrynate ligands (compound 1)
      was shown to be an excellent inhibitor of GST, but did not readily release a PtII
      species to exert a synergistic cytotoxic effect. In this study, a redesigned PtIV
      construct composed of a cDDP core with one axial ethacrynate ligand and one axial
      hydroxido ligand (compound 2) was prepared and shown to overcome the limitations
      of compound 1. The EA ligand in 2 is readily released in vitro together with a
      cytotoxic PtII species derived from cisplatin, working together to inhibit cell
      proliferation in cDDP-resistant human ovarian cancer cells. The in vitro activity
      translates well in vivo with 2, showing effective (~80 %) inhibition of tumor
      growth in a human ovarian carcinoma A2780 tumor model, while showing considerably
      lower toxicity than cisplatin, thus validating the new design strategy.

PMID- 29637703
TI  - Tunable and Photoswitchable Chemically Induced Dimerization for Chemo-optogenetic
      Control of Protein and Organelle Positioning.
AB  - The spatiotemporal dynamics of proteins and organelles play an important role in
      controlling diverse cellular processes. Optogenetic tools using photosensitive
      proteins and chemically induced dimerization (CID), which allow control of
      protein dimerization, have been used to elucidate the dynamics of biological
      systems and to dissect the complicated biological regulatory networks. However,
      the inherent limitations of current optogenetic and CID systems remain a
      significant challenge for the fine-tuning of cellular activity at precise times
      and locations. Herein, we present a novel chemo-optogenetic approach,
      photoswitchable chemically induced dimerization (psCID), for controlling cellular
      function by using blue light in a rapid and reversible manner. Moreover, psCID is
      tunable; that is, the dimerization and dedimerization degrees can be fine-tuned
      by applying different doses of illumination. Using this approach, we control the
      localization of proteins and positioning of organelles in live cells with high
      spatial (MUm) and temporal (ms) precision.

PMID- 29637704
TI  - Enhanced Single-Step Bioproduction of the Simvastatin Precursor Monacolin J in an
      Industrial Strain of Aspergillus terreus by Employing the Evolved Lovastatin
      Hydrolase.
AB  - Biosynthesis of simvastatin, the active pharmaceutical ingredient of cholesterol
      lowering drug Zocor, has drawn increasing global attention in recent years.
      Although single-step in vivo production of monacolin J, the intermediate
      biosynthetic precursor of simvastatin, has been realized by utilizing lovastatin
      hydrolase (PcEST) in our previous study, about 5% of residual lovastatin is still
      a problem for industrial production and quality control. In order to improve
      conversion efficiency and reduce lovastatin residues, modification of PcEST is
      carried out through directed evolution and a novel two-step high-throughput
      screening method. The mutant Q140L shows 18-fold improved whole-cell activity as
      compared to the wild-type, and one fold enhanced catalytic efficiency and 3 
      degrees C increased T5010 over the wild-type are observed by characterizing the
      purified protein. Finally, the engineered A. terreus strain overexpressing Q140L
      mutant exhibited the increased conversion efficiency and the reduced lovastatin
      residues by comparing with A. terreus strain overexpressing the wild-type PcEST,
      where almost 100% of the produced lovastatin is hydrolyzed to monacolin J.
      Therefore, this improved microbial cell factory can realize single-step
      bioproduction of monacolin J in a more efficient way, providing an attractive and
      eco-friendly substitute over the existing chemical synthetic routes of monacolin
      J and promoting complete bioproduction of simvastatin at industrial scale.

PMID- 29637705
TI  - Interactions of the immune and sensory nervous systems in atopy.
AB  - A striking feature underlying all atopic disorders, such as asthma, atopic
      dermatitis, and food allergy, is the presence of pathologic sensory responses,
      reflexes, and behaviors. These symptoms, exemplified by chronic airway irritation
      and cough, chronic itch and scratching, as well as gastrointestinal discomfort
      and dysfunction, are often cited as the most debilitating aspects of atopic
      disorders. Emerging studies have highlighted how the immune system shapes the
      scope and intensity of sensory responses by directly modulating the sensory
      nervous system. Additionally, factors produced by neurons have demonstrated novel
      functions in propagating atopic inflammation at barrier surfaces. In this review,
      we highlight new studies that have changed our understanding of atopy through
      advances in characterizing the reciprocal interactions between the immune and
      sensory nervous systems.

PMID- 29637706
TI  - Editorial.

PMID- 29637707
TI  - The malaria PTEX component PTEX88 interacts most closely with HSP101 at the host
      parasite interface.
AB  - The pathogenic nature of malaria infections is due in part to the export of
      hundreds of effector proteins that actively remodel the host erythrocyte. The
      Plasmodium translocon of exported proteins (PTEX) has been shown to facilitate
      the trafficking of proteins into the host cell, a process that is essential for
      the survival of the parasite. The role of the auxiliary PTEX component PTEX88
      remains unclear, as previous attempts to elucidate its function through reverse
      genetic approaches showed that in contrast to the core components PTEX150 and
      HSP101, knockdown of PTEX88 did not give rise to an export phenotype. Here, we
      have used biochemical approaches to understand how PTEX88 assembles within the
      translocation machinery. Proteomic analysis of the PTEX88 interactome showed that
      PTEX88 interacts closely with HSP101 but has a weaker affinity with the other
      core constituents of PTEX. PTEX88 was also found to associate with other PV
      resident proteins, including chaperones and members of the exported protein
      interacting complex that interacts with the major virulence factor PfEMP1, the
      latter contributing to cytoadherence and parasite virulence. Despite being
      expressed for the duration of the blood-stage life cycle, PTEX88 was only
      discretely observed at the parasitophorous vacuole membrane during ring stages
      and could not always be detected in the major high molecular weight complex that
      contains the other core components of PTEX, suggesting that its interaction with
      the PTEX complex may be dynamic. Together, these data have enabled the generation
      of an updated model of PTEX that now includes how PTEX88 assembles within the
      complex.

PMID- 29637708
TI  - Secretory Overexpression of Bacillus thermocatenulatus Lipase in Saccharomyces
      cerevisiae Using Combinatorial Library Strategy.
AB  - Simple and cost-effective lipase expression host microorganisms are highly
      desirable. A combinatorial library strategy is used to improve the secretory
      expression of lipase from Bacillus thermocatenulatus (BTL2) in the culture
      supernatant of Saccharomyces cerevisiae. A plasmid library including expression
      cassettes composed of sequences encoding one of each 15 promoters, 15 secretion
      signals, and 15 terminators derived from yeast species, S. cerevisiae, Pichia
      pastoris, and Hansenula polymorpha, is constructed. The S. cerevisiae
      transformant YPH499/D4, comprising H. polymorpha GAP promoter, S. cerevisiae SAG1
      secretion signal, and P. pastoris AOX1 terminator, is selected by high-throughput
      screening. This transformant expresses BTL2 extra-cellularly with a 130-fold
      higher than the control strain, comprising S. cerevisiae PGK1 promoter, S.
      cerevisiae alpha-factor secretion signal, and S. cerevisiae PGK1 terminator,
      after cultivation for 72 h. This combinatorial library strategy holds promising
      potential for application in the optimization of the secretory expression of
      proteins in yeast.

PMID- 29637709
TI  - Re-conceptualizing the nursing metaparadigm: Articulating the philosophical
      ontology of the nursing discipline that orients inquiry and practice.
AB  - Jacqueline Fawcett's nursing metaparadigm-the domains of person, health,
      environment, and nursing-remains popular in nursing curricula, despite having
      been repeatedly challenged as a logical philosophy of nursing. Fawcett
      appropriated the word "metaparadigm" (indirectly) from Margaret Masterman and
      Thomas Kuhn as a devise that allowed her to organize then-current areas of
      nursing interest into a philosophical "hierarchy of knowledge," and thereby claim
      nursing inquiry and practice as rigorously "scientific." Scholars have
      consistently rejected the logic of Fawcett's metaparadigm, but have not yet
      proposed a substantially agreed-upon alternative. Through an analysis of articles
      introducing and critiquing Fawcett's metaparadigm, I argue for a re
      conceptualized metaparadigm that articulates nursing's ontology. What exists for
      the nursing discipline are not already-demarcated metaparadigm domains, but
      rather interdependent, dynamic relations that constitute people, including
      nurses, in their health/environment circumstance. The nursing discipline aims to
      skillfully access this dynamic relationality as the basis for action and
      reflection to produce both positive health trajectories and knowledge that
      facilitates future action and reflection. Further inquiry into the onto
      epistemology of nursing will produce a more robust understanding of nursing
      practice, science, and philosophy, and clarify its unique contribution to health
      and healthcare.

PMID- 29637710
TI  - Core Electron Topologies in Chemical Compounds: Case Study of Carbon versus
      Silicon.
AB  - The similarities and differences between carbon and silicon have attracted the
      curiosity of chemists for centuries. Similarities and analogies can be found in
      their saturated compounds, but carbon exhibits a cornucopia of unsaturated
      compounds that silicon (and most other elements) cannot replicate. While this
      qualitative difference is empirically well known, quantum chemistry has
      previously only described quantitative differences related to orbital overlap,
      steric effects, or orbital energies. We study C2 and Si2 and their hydrides X2
      H2n (X=C, Si; n=1, 2, 3) by first-principles quantum chemical calculation, and
      find a qualitative difference in the topologies of the core electrons: carbon has
      the propensity to alter its core electron topology when forming unsaturated
      compounds, and silicon has not. We draw a connection between the core electron
      topologies and ionization energies, and identify other elements we expect to have
      similarly flexible core topologies as carbon.

PMID- 29637712
TI  - Improving clinical outcomes for women with overactive bladder or urinary
      retention symptoms: a comparison of motor response voltages (1-9 V) during Stage
      1 sacral neuromodulation.
AB  - OBJECTIVE: To assess whether the utilisation of a motor response of <3 V during
      Stage 1 sacral neuromodulation (SNM) results in better clinical outcomes compared
      to >4 V in patients with overactive bladder (OAB) or urinary retention symptoms.
      PATIENTS AND METHODS: An observational, retrospective, double cohort review was
      conducted of 339 female patients who had experienced medically recalcitrant OAB
      or urinary retention symptoms. Between September 2001 and September 2014, both
      cohorts underwent successful Stage 1 to Stage 2 SNM placement. Group A, included
      174 women with a motor response at <=3 V; and Group B, evaluated 110 women with a
      motor response at >=4 V for medically recalcitrant OAB. Group C, compared 33
      women with a motor response at <=3 V; and Group D, documented 22 women with a
      motor response at >=4 V for non-obstructive urinary retention. Patients completed
      3-day voiding diaries, the Urogenital Distress Inventory-6 (UDI-6), Incontinence
      Impact Questionnaire-7 (IIQ-7), and Patient Global Impression of Improvement
      Questionnaire. RESULTS: The mean (sd) follow-up was 116.3 (30.3) months in Group
      A and 112 (34.6) months in Group B (P < 0.354); 150.5 (20.4) months in Group C
      and 145.8 (17.2) months in Group D (P < 0.38). Successful conversion of Stage 1
      to Stage 2 showed statistically significant improvement for both <3-V groups
      (Groups A and C). Group A had a 93.5% (174/186) conversion rate vs 72.3%
      (110/152) in Group B for OAB symptoms (P < 0.001). Group C had a 94% (34/36)
      conversion rate vs 70% (21/30) in Group D (P < 0.017). Defined as a >=50%
      reduction in frequency, urgency, urgency incontinence and nocturia, and UDI-6 and
      IIQ-7 scores, the success rate for Group A was 82.1% (143/174) and for Group B
      was 63% (69/110) (P < 0.001). The mean battery life improved in both <3-V cohorts
      (P < 0.001). Annual reprogramming sessions were reduced in Group A and Group C (P
      < 0.001). Subset analysis of variance showed no statistical improvement in most
      patient outcomes when 1-V subjects were compared to 2- and 3-V cohorts. However,
      32% of 1-V patients (P < 0.001) noted the onset of severe pelvic/perirectal pain
      and big toe plantar flexion movement with small increments in voltage (0.1-0.2 V)
      during reprogramming. Only 7% of 2-V and 1% of 3-V patients experienced this
      complication. CONCLUSIONS: Significant improvement was noted (up to 40%) in most
      clinical voiding parameters in the <3-V patients for both OAB and urinary
      retention. While <3 V will still statistically improve patient outcomes, a
      voltage <2 V may elicit self-reprogramming pain with severe bellows and plantar
      flexion movement, which may discourage patients from therapy adjustments. We
      recommend randomised, controlled trials to confirm these results.

PMID- 29637713
TI  - Synthesis and Biological Evaluation of Indole-2-carbohydrazide Derivatives as
      Anticancer Agents with Anti-angiogenic and Antiproliferative Activities.
AB  - A novel series of indole-2-carbohydrazide derivatives were synthesized,
      characterized, and evaluated for their antiproliferative activities against two
      cancer cell lines, HCT116 and SW480, and a normal human fetal lung fibroblast
      cell line, MRC-5. Among this series, compound 24 f displayed potent cytotoxic
      activities in vitro against HCT116 and SW480 cell lines with GI50 values of 8.1
      and 7.9 MUm, respectively, and was inactive against MRC-5 cells. The newly
      synthesized compounds were also evaluated for anti-angiogenesis capabilities by
      chick chorioallantoic membrane, human umbilical vein endothelial cell (HUVEC)
      migration, and endothelial microtubule formation assays. Moreover, the effects of
      24 f on the vascular endothelial growth factor receptor-2 and the signaling
      pathway in HUVECs indicated that this compound inhibits VEGFR-2 and its
      downstream related proteins. These results indicate that compound 24 f, as well
      as the other derivatives, are promising inhibitors of angiogenesis.

PMID- 29637714
TI  - A phase I/II, double-blind, placebo-controlled study assessing safety and
      efficacy of C1 esterase inhibitor for prevention of delayed graft function in
      deceased donor kidney transplant recipients.
AB  - Delayed graft function (DGF) is defined as need for dialysis early
      posttransplant. DGF is related to ischemia-reperfusion injury (IRI) that
      diminishes allograft function and may be complement dependent. Here, we
      investigate the ability of C1 esterase inhibitor (C1INH) to prevent IRI/DGF in
      kidney transplant recipients. Seventy patients receiving deceased donor kidney
      transplants at risk for DGF were randomized to receive C1INH 50 U/kg (#35) or
      placebo (#35) intraoperatively and at 24 hours. The primary end point was need
      for hemodialysis during the first week posttransplant. Assessments of glomerular
      filtration rate and dialysis dependence were accomplished. Complications and
      safety of therapy were recorded. Similar characteristics with no significant
      differences in cold-ischemia time or risk factors for DGF were seen. C1INH did
      not result in reduction of dialysis sessions at 1 week posttransplant, but
      significantly fewer dialysis sessions (P = .0232) were required 2 to 4 weeks
      posttransplant. Patients at highest risk for DGF (Kidney Donor Profile Index
      >=85) benefited most from C1INH therapy. Significantly better renal function was
      seen at 1 year in C1INH patients (P = .006). No significant adverse events were
      noted with C1INH. Although the primary end point was not met, significant
      reductions in need for dialysis and improvements in long-term allograft function
      were seen with C1INH treatment.

PMID- 29637715
TI  - Cytological features of hepatoid adenocarcinoma of the gallbladder: A case report
      with immunocytochemical analyzes.
AB  - Hepatoid adenocarcinoma is defined as an extrahepatic malignant neoplasm showing
      morphological and immunohistochemical resemblance of hepatocellular carcinoma.
      The occurrence of this type of tumor in the gallbladder is extremely rare. In
      this study, we report the first cytological case of hepatoid adenocarcinoma of
      the gallbladder. An 80-year-old Japanese female was found to have a tumorous
      lesion in the gallbladder. Papanicolaou smear of the ascites demonstrated a few
      epithelial cell clusters composed of round to oval neoplastic cells with distinct
      cell border and large centrally-located nuclei. Tumor touch smear of the resected
      tumor revealed the presence of two distinct neoplastic components. The first
      component was composed of clusters or sheets of epithelial cells with distinct
      cell border, relatively rich clear cytoplasm, and centrally-located nuclei, as
      seen in the ascites specimen. The other component was composed of tall columnar
      cells with large basally-oriented nuclei, and glandular formation was noted as
      well. Immunocytochemical analyzes of the touch smear material demonstrated that
      the former component was positive for HepPar1, thus it was considered as a
      hepatoid adenocarcinoma, and the latter component deemed as a typical
      adenocarcinoma. Histopathological and immunohistochemical examination of the
      resected gallbladder tumor confirmed a diagnosis of hepatoid adenocarcinoma. The
      characteristic cytological features of hepatoid adenocarcinoma are the presence
      of sheets or clusters of neoplastic cells with distinct cell border and centrally
      located nuclei. Immunocytochemical analysis for HepPar1 may help its diagnosis.
      Demonstration of hepatoid adenocarcinoma is important in the cytological specimen
      because this type of tumor shows an aggressive clinical course.

PMID- 29637716
TI  - Antishear Stress Bionic Carbon Nanotube Mesh Coating with Intracellular
      Controlled Drug Delivery Constructing Small-Diameter Tissue-Engineered Vascular
      Grafts.
AB  - Small-diameter (<6 mm) tissue-engineered blood vessels (TEBVs) have a low patency
      rate due to chronic inflammation mediated intimal hyperplasia. Functional coating
      with drug release is a promising solution, but preventing the released drug from
      being rushed away by blood flow remains a great challenge. A single-walled
      carboxylic acid functionalized carbon nanotube (C-SWCNT) is used to build an
      irregular mesh for TEBV coating. However, an interaction between the released
      drug and the cells is still insufficient due to the blood flow. Thus, an
      intracellular drug delivery system mediated by macrophage cellular uptake is
      designed. Resveratrol (RSV) modified CNT is used for macrophage uptake. M1
      macrophage uptakes CNT-RSV and then converts to the M2 phenotype upon
      intracellular RSV release. Prohealing M2 macrophage inhibits the chronic
      inflammation thus maintains the contractile phenotype of the vascular smooth
      muscle cell (VSMC), which reduces intimal hyperplasia. Additionally, RSV released
      from the mesh coating also directly protects the contractile VSMCs from being
      converted to a secretory phenotype. Through antishear stress coating and
      macrophage-based intracellular drug delivery, CNT-RSV TEBVs exhibit a long-term
      anti-intimal hyperplasia function. Animal transplantation studies show that the
      patency rate remains high until day 90 after grafting in rat carotid arteries.

PMID- 29637717
TI  - Chemotherapeutic Drug-Conjugated Microbeads Demonstrate Preferential Binding to
      Methylated Plasmid DNA.
AB  - Plasmid DNA (pDNA) is an attractive therapeutic biomolecule in several diseases
      including cancer, AIDS, cystic fibrosis, Parkinson's disease, and Alzheimer's
      disease. Increasing demand for plasmid DNA as a therapeutic biomolecule for
      transgene expression or vaccine applications necessitate novel approaches to
      bioprocessing. The synthesis, characterization and evaluation of aminoglycoside
      derived hydrogel microbeads (Amikabeads) for pDNA binding is described
      previously. Here, the generation and evaluation of novel chemotherapeutic drug
      conjugated microbeads for application in pDNA binding and recovery is described.
      Chemotherapeutic drug-conjugated Amikabeads demonstrate higher binding of
      methylated pDNA compared to unmethylated pDNA in presence of high salt
      concentrations. Desorption of plasmids from drug-conjugated microbeads is
      facilitated by the use of organic modifiers. The observed differences in binding
      methylated versus unmethylated DNA can make drug-conjugated microbeads useful in
      diagnostic as well as therapeutic applications. These results demonstrate that
      anti-cancer drugs represent a diverse set of ligands that may be exploited for
      molecular engineering of novel DNA binding materials for applications in
      delivery, diagnostics, and biomanufacturing.

PMID- 29637718
TI  - Empathy and face processing in adults with and without autism spectrum disorder.
AB  - : Many factors contribute to social difficulties in individuals with autism
      spectrum disorder (ASD). The goal of the present work was to determine whether
      atypicalities in how individuals with ASD process static, socially engaging faces
      persist when nonrigid facial motion cues are present. We also sought to explore
      the relationships between various face processing abilities and individual
      differences in autism symptom severity and traits such as empathy. Participants
      included 16 adults with ASD without intellectual impairment and 16 sex- and age
      matched controls. Mean Verbal IQ was comparable across groups [t(30) = 0.70, P =
      0.49]. The two groups responded similarly to many of the experimental
      manipulations; however, relative to controls, participants with ASD responded
      more slowly to dynamic expressive faces, even when no judgment was required; were
      less accurate at identity matching with static and dynamic faces; and needed more
      time to make identity and expression judgments [F(1, 30) >= 6.37, P <= 0.017,
      etap2  >= 0.175 in all cases], particularly when the faces were moving [F(1, 30)
      = 3.40, P = 0.072, etap2  = 0.104]. In the full sample, as social autistic traits
      increased and empathic skills declined, participants needed more time to judge
      static identity, and static or dynamic expressions [0.43 < |rs | < 0.56]. The
      results suggest that adults with ASD show general impairments in face and motion
      processing and support the view that an examination of individual variation in
      particular personality traits and abilities is important for advancing our
      understanding of face perception. Autism Res 2018, 11: 942-955. (c) 2018
      International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY:
      Our findings suggest that people with ASD have problems processing expressive
      faces, especially when seen in motion. It is important to learn who is most at
      risk for face processing problems, given that in the general population such
      problems appear to be linked to impaired social skills and empathy. By studying
      relationships between different abilities and traits, we may be able to find
      better ways to diagnose and support all people on the autism spectrum.

PMID- 29637719
TI  - Transient Expression of Human Cytochrome P450s 2D6 and 3A4 in Nicotiana
      benthamiana Provides a Possibility for Rapid Substrate Testing and Production of
      Novel Compounds.
AB  - Employment of transient expression of foreign genes for bioconversion of
      pharmaceutically valuable low-molecular-weight compounds, including plant
      secondary metabolites, is an enticing trend still scantily explored in plant
      biotechnology. In the present work, an efficient protocol for rapid assessment of
      synthetic and plant-derived metabolites as potential substrates for human P450s
      (CYP2D6 and CYP3A4) via Agrobacterium-mediated transient expression in Nicotiana
      benthamiana is put forth. Animal P450s with broad substrate specificity are
      promising candidates for transformation of diverse metabolites. The efficiency of
      P450s in heterologous surroundings is not always satisfactory and depends on the
      availability of an associated electron-transfer enzyme. Plants represent an
      attractive assortment of prospective hosts for foreign P450s expression. The
      optimal composition of genetic blocks providing the highest transient expression
      efficiency is designed, an effective substrate administration scheme is
      validated, and biological activity of the investigated P450s against loratadine
      and several indole alkaloids with different molecular scaffold structures is
      tested. A novel indole alkaloid, 11-hydroxycorynanthine, is isolated from N.
      benthamiana plants transiently expressing CYP2D6 and supplemented with
      corynanthine, and its structure was elucidated. The proposed technique might be
      of value in realization of combinatorial biosynthesis concept comprising the
      junction of heterologous enzymes and substrates in different metabolic
      surroundings.

PMID- 29637711
TI  - A guide to chemokines and their receptors.
AB  - The chemokines (or chemotactic cytokines) are a large family of small, secreted
      proteins that signal through cell surface G protein-coupled heptahelical
      chemokine receptors. They are best known for their ability to stimulate the
      migration of cells, most notably white blood cells (leukocytes). Consequently,
      chemokines play a central role in the development and homeostasis of the immune
      system, and are involved in all protective or destructive immune and inflammatory
      responses. Classically viewed as inducers of directed chemotactic migration, it
      is now clear that chemokines can stimulate a variety of other types of directed
      and undirected migratory behavior, such as haptotaxis, chemokinesis, and
      haptokinesis, in addition to inducing cell arrest or adhesion. However, chemokine
      receptors on leukocytes can do more than just direct migration, and these
      molecules can also be expressed on, and regulate the biology of, many
      nonleukocytic cell types. Chemokines are profoundly affected by post
      translational modification, by interaction with the extracellular matrix (ECM),
      and by binding to heptahelical 'atypical' chemokine receptors that regulate
      chemokine localization and abundance. This guide gives a broad overview of the
      chemokine and chemokine receptor families; summarizes the complex physical
      interactions that occur in the chemokine network; and, using specific examples,
      discusses general principles of chemokine function, focusing particularly on
      their ability to direct leukocyte migration.

PMID- 29637720
TI  - Pediatric cirrhotic cardiomyopathy: Impact on liver transplant outcomes.
AB  - In adults, cirrhotic cardiomyopathy (CCM) has a significant incidence and impact
      on liver transplantation. For pediatric liver transplantation (pLT), data on
      liver-induced cardiac changes are scarce, and in particular, the comparison
      between cirrhotic and noncirrhotic liver disease has not been investigated. We
      retrospectively evaluated cardiac changes associated with CCM by echocardiography
      and 12-lead electrocardiogram in 198 pLT-candidates (median age 4.1 years) 4.2
      before and 12 months after pLT. Results were correlated with the stage of liver
      fibrosis and cholestasis before transplantation. The left ventricular end
      diastolic diameter (LVIDd) z score, left ventricular mass z score, and left
      ventricular mass index were significantly higher in cirrhotic patients (-0.10
      versus 0.98, P < 0.001; -1.55 versus -0.42, P = 0.001; 78.99 versus 125.64 g/m2 ,
      P = 0.001, respectively) compared with children with noncirrhotic liver disease.
      Pathological z scores (>2SDS) for the LVIDd occurred more frequently in cirrhotic
      patients compared with patients with noncirrhotic liver disease (31/169 versus
      1/29; P = 0.03) and were significantly associated with cholestasis. All observed
      cardiac changes were reversible 1 year after pLT. Pathological LVIDd z scores
      correlated highly with intensive care unit (ICU) stay (9.6 days versus 17.1 days,
      respectively, P = 0.002) but not with patient survival pre-LT or post-LT. In
      contrast to other studies, prolonged QTc time was not associated with liver
      cirrhosis in our patients. In conclusion, CCM-associated cardiac changes in pLT
      candidates with cirrhotic liver disease are frequent, mild, and associated with
      cholestasis and reversible after pLT. They may impact peritransplant care and
      posttransplant hospitalization time. Further prospective evaluation is warranted.
      In particular, for QTc time prolongation etiological factors, possible protective
      effects of ursodeoxycholic acid treatment and the use as a screening parameter
      for CCM should be verified. Liver Transplantation 24 820-830 2018 AASLD.

PMID- 29637721
TI  - Presumed missense and synonymous mutations in ATP7B gene cause exon skipping in
      Wilson disease.
AB  - BACKGROUND & AIMS: Wilson disease is an inborn error of metabolism caused by
      abnormalities of the copper-transporting protein-encoding gene ATP7B. Recently,
      the phenomenon of exon skipping, in which exonic mutations result in abnormal
      splicing, has been associated with various diseases. The present study
      investigated the splicing defects of the ATP7B exonic variants identified in a
      cohort of 44 patients with Wilson disease. METHOD: All patients were analysed for
      ATP7B gene by direct sequencing or multiplex ligation-dependent probe
      amplification analysis. To identify the potential pathogenicity of the candidate
      mutations that may induce exon skipping, both in vivo RT-PCR analysis using RNA
      from peripheral leukocytes and in vitro functional splicing by minigene
      construction were conducted. RESULTS: The patterns of inheritance of the
      mutations in ATP7B identified in 44 patients exhibited homozygotes (7 patients),
      compound heterozygotes (32 patients) and heterozygotes (5 patients). In all
      patients, we detected 25 different ATP7B mutations, including 17 missenses, 1
      frameshift, 3 nonsenses, 2 exonic deletions and 2 splicing alteration. In these
      mutations, 4 mutations have not been previously described in the literature or
      entered in human genome mutation database. Furthermore, we identified synonymous
      mutation c.4014T>A and missense mutation R919G caused exon skipping in the ATP7B
      mRNA transcript. CONCLUSION: Our results suggest that aberrant exon skipping
      associated to putative splicing enhancer disruption and silencer creation is one
      previously unrecognized mechanism in Wilson disease. What is more, the multiplex
      ligation-dependent probe amplification assay for the detection of exon deletions
      may be valuable in individuals with clinical Wilson disease diagnosis where one
      or no mutation has been identified by sequencing.

PMID- 29637723
TI  - Response to Alwardat comments on our systematic review entitled: "Predictors of
      adherence to exercise interventions during and after cancer treatment: A
      systematic review".

PMID- 29637722
TI  - Mixed intoxication by the synthetic opioid U-47700 and the benzodiazepine
      flubromazepam with lethal outcome: Pharmacokinetic data.
AB  - Novel synthetic opioids and benzodiazepines are an emerging trend on the narcotic
      drugs market. We present a lethal case of U-47700 and flubromazepam poisoning. A
      24-year-old man suffered apnoea after the consumption of the synthetic opioid U
      47700 in combination with the benzodiazepine flubromazepam. After reanimation and
      hospital admission, hypoxic cerebral damage and severe brain oedema were stated.
      Six days after admission, mechanical ventilation was discontinued, and the
      patient died. Seven blood serum samples and one urine sample collected during the
      hospitalisation were analysed by liquid chromatography-tandem mass spectrometry.
      In the sample collected 42 minutes after admission, the concentrations of U-47700
      and flubromazepam were 370 and 830 ng/mL, respectively. Three days later, the
      concentrations of U-47700 and flubromazepam dropped to 4.2 and 280 ng/mL,
      respectively. The resulting concentration-time-curves allowed calculating a U
      47700 elimination half-life of approximately six hours and confirmed the
      previously reported flubromazepam elimination half-life of around 100 hours. In
      the presented case, intoxication by the synthetic opioid U-47700 with a
      contribution of flubromazepam can be assumed as the cause of death. The
      concentration-time curves allow an estimation of the clinical course of similar
      cases. Flubromazepam may lead to prolonged central-nervous depressant effects.

PMID- 29637724
TI  - Is a meta-analytic approach to burnout's prevalence timely?

PMID- 29637726
TI  - Comments on: "Predictors of adherence to exercise interventions during and after
      cancer treatment: A systematic review".

PMID- 29637727
TI  - WHO model of intrapartum care for a positive childbirth experience: transforming
      care of women and babies for improved health and wellbeing.

PMID- 29637728
TI  - Molecular testing for indeterminate thyroid nodules: Performance of the Afirma
      gene expression classifier and ThyroSeq panel.
AB  - BACKGROUND: The ThyroSeq mutational panel and Afirma gene expression classifier
      (GEC) are used to risk stratify cytologically indeterminate thyroid nodules. In
      the current study, the authors evaluated the performance of these tests within
      the context of ultrasonographic features and with the incorporation of the
      noninvasive follicular thyroid neoplasm with papillary-like nuclear features
      (NIFTP) nomenclature. METHODS: The authors reviewed nodules using ThyroSeq or
      Afirma GEC testing. For nodules that were surgically resected, both tests were
      studied within the context of ultrasound findings, comparing performance
      stratified by the 2015 American Thyroid Association guideline (ATA 2015)
      sonographic patterns and assessing the positive predictive value (PPV) of these
      tests both including and excluding NIFTP in the malignant category. RESULTS: A
      total of 304 cases were identified, 119 of which were resected. All cases that
      met the criteria for NIFTP on excision demonstrated either high-risk mutations on
      ThyroSeq or a "suspicious" result on Afirma GEC. When NIFTP cases were shifted
      from the malignant to nonmalignant category, the PPV of "positive" tests for both
      ThyroSeq and Afirma GEC decreased from 42.9% to 14.3% (an absolute decrease of
      28.6%) and 30.1% to 25.3% (an absolute decrease of 4.8%), respectively. No cases
      of malignancy were found in the ATA 2015 "very low suspicion" group, even with a
      "suspicious" Afirma GEC result. CONCLUSIONS: Both the ThyroSeq and Afirma GEC
      tests demonstrated decreases in the PPV when NIFTP was considered nonmalignant.
      In the era of NIFTP, a "positive" test result for either the Afirma GEC or
      ThyroSeq should be interpreted in light of clinical factors and should not
      exclude conservative (ie, lobectomy) surgical management. ATA 2015 "very low
      suspicion" nodules, even with "suspicious" Afirma GEC results, were not found to
      demonstrate malignancy in this series. Cancer Cytopathol 2018. (c) 2018 American
      Cancer Society.

PMID- 29637730
TI  - Living Donation Versus Donation After Circulatory Death Liver Transplantation for
      Low MELD Recipients.
AB  - Background In this era of organ scarcity, living donor liver transplant (LDLT) is
      an alternative to using deceased donors and in Western countries is more often
      used in low model for end-stage liver disease (MELD) recipients. We sought to
      compare the patient survival and graft survival between recipients of liver
      transplantation from living donors and donation after circulatory death (DCD)
      donors in patients with low MELD scores. Methods Retrospective cohort analysis of
      adult liver transplant recipients with a laboratory MELD <= 20 who underwent
      transplantation between 01/01/2003 and 03/31/2016. Recipients were categorized by
      donor graft type (DCD or LDLT) and recipient and donor characteristics were
      compared. Ten-year patient and graft survival curves were calculated using Kaplan
      Meier analyses and a mixed-effects model was performed to determine the
      contributions of recipient, donor and center variables on patient and graft
      survival. Results 36,705 liver transplants were performed - 2,166 (5.9%) were
      from DCD donors and 2,284 (6.2%) from living donors. In the mixed-effects model,
      DCD status was associated with a higher risk of graft failure (RR 1.27, 95% CI
      1.16-1.38) but not worse patient survival (RR 1.27, 95% CI: 0.96-1.67). Lower DCD
      center experience was associated with a 1.21 higher risk of patient death (95%
      CI: 1.17-1.25) and 1.13 higher risk of graft failure (95% CI: 1.12-1.15). LDLT
      center experience was also predictive of patient survival (RR 1.03, 95% CI: 1.02
      1.03) and graft failure (RR 1.05, 95% CI: 1.05-1.06). Conclusion For liver
      transplant recipients with low laboratory MELD, LDLT offers better graft survival
      and a tendency to better patient survival than DCD donors. This article is
      protected by copyright. All rights reserved.

PMID- 29637729
TI  - High-density genetic map using whole-genome resequencing for fine mapping and
      candidate gene discovery for disease resistance in peanut.
AB  - Whole-genome resequencing (WGRS) of mapping populations has facilitated
      development of high-density genetic maps essential for fine mapping and candidate
      gene discovery for traits of interest in crop species. Leaf spots, including
      early leaf spot (ELS) and late leaf spot (LLS), and Tomato spotted wilt virus
      (TSWV) are devastating diseases in peanut causing significant yield loss. We
      generated WGRS data on a recombinant inbred line population, developed a SNP
      based high-density genetic map, and conducted fine mapping, candidate gene
      discovery and marker validation for ELS, LLS and TSWV. The first sequence-based
      high-density map was constructed with 8869 SNPs assigned to 20 linkage groups,
      representing 20 chromosomes, for the 'T' population (Tifrunner * GT-C20) with a
      map length of 3120 cM and an average distance of 1.45 cM. The quantitative trait
      locus (QTL) analysis using high-density genetic map and multiple season
      phenotyping data identified 35 main-effect QTLs with phenotypic variation
      explained (PVE) from 6.32% to 47.63%. Among major-effect QTLs mapped, there were
      two QTLs for ELS on B05 with 47.42% PVE and B03 with 47.38% PVE, two QTLs for LLS
      on A05 with 47.63% and B03 with 34.03% PVE and one QTL for TSWV on B09 with
      40.71% PVE. The epistasis and environment interaction analyses identified
      significant environmental effects on these traits. The identified QTL regions had
      disease resistance genes including R-genes and transcription factors. KASP
      markers were developed for major QTLs and validated in the population and are
      ready for further deployment in genomics-assisted breeding in peanut.

PMID- 29637731
TI  - Automatic estimation of Purkinje-Myocardial junction hot-spots from noisy
      endocardial samples: A simulation study.
AB  - The reconstruction of the ventricular cardiac conduction system (CCS) from
      patient-specific data is a challenging problem. High-resolution imaging
      techniques have allowed only the segmentation of proximal sections of the CCS
      from images acquired ex vivo. In this paper, we present an algorithm to estimate
      the location of a set of Purkinje-myocardial junctions (PMJs) from electro
      anatomical maps, as those acquired during radio-frequency ablation procedures.
      The method requires a mesh representing the myocardium with local activation time
      measurements on a subset of nodes. We calculate the backwards propagation of the
      electrical signal from the measurement points to all the points in the mesh to
      define a set of candidate PMJs that is iteratively refined. The algorithm has
      been tested on several Purkinje network configurations, with simulated activation
      maps, subject to different error amplitudes. The results show that the method is
      able to build a set of PMJs that explain the observed activation map for
      different synthetic CCS configurations. In the tests, the average error in the
      predicted activation time is below the amplitude of the error applied to the
      data.

PMID- 29637732
TI  - Quantitative Systems Pharmacology Model of hUGT1A1-modRNA Encoding for the UGT1A1
      Enzyme to Treat Crigler-Najjar Syndrome Type 1.
AB  - Crigler-Najjar syndrome type 1 (CN1) is an autosomal recessive disease caused by
      a marked decrease in uridine-diphosphate-glucuronosyltransferase (UGT1A1) enzyme
      activity. Delivery of hUGT1A1-modRNA (a modified messenger RNA encoding for
      UGT1A1) as a lipid nanoparticle is anticipated to restore hepatic expression of
      UGT1A1, allowing normal glucuronidation and clearance of bilirubin in patients.
      To support translation from preclinical to clinical studies, and first-in-human
      studies, a quantitative systems pharmacology (QSP) model was developed. The QSP
      model was calibrated to plasma and liver mRNA, and total serum bilirubin in Gunn
      rats, an animal model of CN1. This QSP model adequately captured the observed
      plasma and liver biomarker behavior across a range of doses and dose regimens in
      Gunn rats. First-in-human dose projections made using the translated model
      indicated that 0.5 mg/kg Q4W dose should provide a clinically meaningful and
      sustained reduction of >5 mg/dL in total bilirubin levels.

PMID- 29637733
TI  - Ocular implant containing bevacizumab-loaded chitosan nanoparticles intended for
      choroidal neovascularization treatment.
AB  - Choroidal neovascularization (CNV) is among the leading causes of blindness
      worldwide. Bevacizumab has demonstrated promising effects on CNV treatment;
      however, frequent intravitreal injection is its major drawback. Current study
      aimed to address this issue by developing a sustained release formulation through
      nanoparticles of bevacizumab imbedded in an ocular implant. Bevacizumab-loaded
      chitosan nanoparticles were prepared by ionic gelation method and inserted in the
      matrix of hyaluronic acid and zinc sulfate. Despite the common approaches in
      using ultraviolet (UV)-spectrophotometry, microprotein-Bradford, and
      bicinchoninic acid (BCA), assay for protein assessment, our results revealed a
      remarkable UV-Vis absorption overlap of protein and chitosan during these
      analysis and thus enzyme-linked immunosorbent assay was employed for the antibody
      concentration assay. The size of optimized nanoparticles obtained through
      statistical analysis based on design of experiments was 78.5 +/- 1.9 nm with
      polydispersity index of 0.13 +/- 0.05 and the entrapment-efficiency and loading
      efficiency were 67.6 +/- 6.7 and 15.7 +/- 5.7%, respectively. The scanning
      electron microscopy and confocal microscopy images revealed a homogenous
      distribution of nanoparticles in the implant matrix and the release test results
      indicated an appropriate extended release of bevacizumab from the carrier over
      two months. In conclusion, the prepared system provided a sustained release
      bevacizumab delivery formulation which can introduce a promising ocular drug
      delivery system intended for posterior segment disease. (c) 2018 Wiley
      Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2261-2271, 2018.

PMID- 29637734
TI  - Metabolic Adaptations to Weight Loss.

PMID- 29637735
TI  - Copy number gain in recurrent anaplastic lymphoma kinase (ALK) rearrangement-lung
      adenocarcinoma in the pleural effusion.
AB  - Copy number gain (CNG), which includes both numerical and structural chromosomal
      abnormalities, has been investigated in many human cancers. We report a case of
      recurrence of anaplastic lymphoma kinase (ALK) rearrangement-positive lung
      adenocarcinoma with increased cellular pleomorphism and ALK copy number in
      pleural effusion cytology, and retrospectively compared the recurrent tumor with
      the primary tumor in terms of cytological features, immunohistochemistry (IHC)
      and fluorescence in situ hybridization (FISH). The patient was a woman in her 50s
      who was found to have a 20 * 20 mm sized mass in the lung by chest computed
      tomography (CT), and was diagnosed with ALK rearrangement-positive lung
      adenocarcinoma. The patient was administered ALK inhibitors, such as alectinib,
      however 4 years later dissemination to the pleural effusion was detected. The
      smear was of high cellularity, and a predominant population of large-sized
      pleomorphic adenocarcinoma cells with prominent nucleoli was observed. On FISH
      and IHC using cell block material, ALK rearrangement and ALK protein expression
      were identified again, along with recurrent ALK adenocarcinoma cells, which were
      observed to have an increased ALK copy number compared with the primary ALK
      adenocarcinoma cells. On the other hand, there was no discrepancy in the
      expression of various biomarkers between the primary and corresponding recurrent
      tumor. The present case showed a marked difference in cytological findings and
      CNG between the primary and recurrent tumor, indicating that DNA aneuploidy may
      be related to morphological change such as transformation to bizarre pleomorphic
      cells in patients receiving alectinib treatment.

PMID- 29637736
TI  - A ternary nanofibrous scaffold potential for central nerve system tissue
      engineering.
AB  - In the present research, a ternary polycaprolactone (PCL)/gelatin/fibrinogen
      nanofibrous scaffold for tissue engineering application was developed. Through
      this combination, PCL improved the scaffold mechanical properties; meanwhile,
      gelatin and fibrinogen provided more hydrophilicity and cell proliferation. Three
      types of nanofibrous scaffolds containing different fibrinogen contents were
      prepared and characterized. Morphological study of the nanofibers showed that the
      prepared nanofibers were smooth, uniform without any formation of beads with a
      significant reduction in nanofiber diameter after incorporation of fibrinogen.
      The chemical characterization of the scaffolds confirmed that no chemical
      reaction occurred between the scaffold components. The tensile test results of
      the scaffolds showed that increasing in fibrinogen content led to a decrease in
      mechanical properties. Furthermore, adipose-derived stem cells were employed to
      evaluate cell-scaffold interaction. Cell culture results indicated that higher
      cell proliferation occurred for the higher amount of fibrinogen. Statistical
      analysis was also carried out to evaluate the significant difference for the
      obtained results of water droplet contact angle and cell culture. Therefore, the
      results confirmed that PCL/gel/fibrinogen scaffold has a good potential for
      tissue engineering applications including central nerve system tissue
      engineering. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A:
      106A:2394-2401, 2018.

PMID- 29637737
TI  - Fabrication and evaluation of a nerve guidance conduit capable of Ca2+ ion
      release to accelerate axon extension in peripheral nerve regeneration.
AB  - In this study, biodegradable nanocomposites consisting of poly (glycerol
      sebacate) (PGS) elastomeric matrix and the reinforcing phase of calcium titanate
      (CaTiO3 ) nanoparticles were fabricated as a nerve guidance conduit (NGC) for
      peripheral nerve regeneration. CaTiO3 nanoparticles were synthesized via the sol
      gel method and calcined at 800 degrees C for 60 min. PGS elastomer was
      synthesized via the polycondensation reaction of glycerol and sebacate (1:1) and
      2.5 and 5 wt. percentages of the synthesized CaTiO3 nanoparticles were added to
      the PGS prepolymer solution. The composites obtained were heated in order to make
      crosslinks in the pre-polymer. CaTiO3 nanoparticles, PGS elastomer, and the
      composites fabricated were characterized in terms of their structural, chemical,
      physical, mechanical, and cell response properties to evaluate the feasibility of
      using the nanocomposite for NGC applications. The results indicated that CaTiO3
      nanoparticles were 50 nm in size. When the nanoparticles were added to the PGS,
      the elastic modulus and tensile strength of the nanocomposite reached values of
      about 1 and 0.5 MPa, respectively that are near those of natural nerves. The
      degradation behavior and swelling of the nanocomposites, as compared with those
      of the PGS elastomer, were controlled by introducing CaTiO3 into the PGS, which
      swelling limitation could prevent nerve compression. It was observed that Ca2+
      ions established chemical bonds with PGS, which led to high crosslink densities
      that, in turn, contribute to improved mechanical properties of the composite. The
      Ca2+ ions released from the nanocomposite samples were in the nontoxic range. The
      PC12 cell line on the surface of the nanocomposite specimens showed good cell
      adhesion and proliferation with improved axon outgrowth and extension. Based on
      the results obtained the fabricated PGS/CaTiO3 nanocomposite may be recommended
      as a suitable NGC with desirable effects on peripheral nerve regeneration. (c)
      2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2181-2189, 2018.

PMID- 29637738
TI  - A collagen based cryogel bioscaffold coated with nanostructured polydopamine as a
      platform for mesenchymal stem cell therapy.
AB  - Cryo-hydrogels (cryogels) are polymer hydrogels formed at sub-zero temperatures.
      Bioscaffolds created from cryogels have interconnected macropores which allow for
      cell migration, tissue-ingrowth, unhindered diffusion of solutes and mass
      transport of therapeutics. In this study, we developed collagen based cryogel
      bioscaffolds and coated them with polydopamine using a simple two-step technique.
      Cryogel bioscaffolds were synthesized by collagen crosslinking at -20 degrees C
      and exhibited a macroporous interconnected architecture with 75% +/- 3% porosity.
      Two groups of pore sizes were observed: 300 +/- 50 um and 30 +/- 10 um in
      diameter. The addition of a polydopamine coating to cryogel bioscaffolds was
      confirmed using composition analysis. This resulted in a 41% +/- 5% decrease in
      water uptake, 81% +/- 10% decrease in swelling rate and 12% +/- 3% decrease in
      their degree of dissolution (p < 0.05), with a 48% +/- 2% increase in stiffness
      and 57% +/- 5% increase in compressive strength (p < 0.05). Seeding adipose
      tissue-derived mesenchymal stem cells (AD-MSCs) into polydopamine coated-cryogel
      bioscaffolds resulted in cells demonstrating a 52% +/- 4% increase in viability
      and 33% +/- 3% increase in proliferation when compared to AD-MSCs seeded into
      uncoated-cryogel bioscaffolds (p < 0.05). In summary, our novel polydopamine
      coated-cryogel bioscaffold represents an efficient and low-cost bioscaffold
      platform to support MSC therapies. (c) 2018 Wiley Periodicals, Inc. J Biomed
      Mater Res Part A: 106A: 2213-2228, 2018.

PMID- 29637739
TI  - Initial Clinical Experience of RP5063 Following Single Doses in Normal Healthy
      Volunteers and Multiple Doses in Patients with Stable Schizophrenia.
AB  - RP5063 is a multimodal dopamine (D)-serotonin (5-HT) stabilizer with a high
      affinity for D2/3/4 and 5-HT1A/2A/2B/7 receptors and moderate affinity for the
      serotonin transporter. Single-dose (10 and 15 mg fasting, 15 mg fed) safety in
      healthy volunteers and multiple-dose (10, 20, 50, and 100 mg fed, 10 days) safety
      and pharmacodynamics in patients with stable schizophrenia were defined in two
      phase I studies. In the single-dose study, 32 treatment-emergent adverse events
      (TEAEs) were observed. Orthostatic hypotension (n = 6), nausea (n = 5), and
      dizziness (n = 4) were the most common. One serious adverse event (SAE), seen in
      a patient who should not have been in the study due to a history of seizures,
      involved brief seizure-like symptoms. In the multiple-dose study, 75 TEAEs were
      reported. Akathisia (n = 20) and somnolence (n = 14) were the most frequent. No
      clinically significant changes were seen in glucose or prolactin levels, lipid
      profiles, weight, or electrocardiographic recordings. In both studies, all TEAEs
      resolved and none led to withdrawal from the study or death. A pharmacodynamic
      evaluation reflected significant improvements with RP5063 (P < 0.05) over placebo
      in an analysis of patients with a baseline Positive and Negative Syndrome Scale
      (PANSS) score >=50 for positive subscale scores. Improvements of the Trail Making
      A and Trail Making B test results were observed for patients treated in the 50 mg
      dose group for days 5, 10, and 16. These findings indicate that RP5063 is well
      tolerated up to 100 mg and displays promising preliminary clinical behavioral and
      cognition activity signals in patients with stable disease over a 10-day period.

PMID- 29637741
TI  - Tropical Medicine & International Health.

PMID- 29637740
TI  - Corrigendum.

PMID- 29637742
TI  - Effect of resveratrol on doxorubicin resistance in breast neoplasm cells by
      modulating PI3K/Akt signaling pathway.
AB  - In the study, we probed into the effect of Resveratrol (RES) on Doxorubicin (DOX)
      resistant breast neoplasm cell line MCF-7/DOX as well as the mechanism of RES
      underlying the DOX-resistant breast cancer. CCK-8 assay was utilized to assess
      the survival rates and sensitivity of breast neoplasm cell lines MCF-7 or MDA-MB
      231 to DOX and RES. DOX-resistant MCF-7 cell line was successfully cultivated
      with DOX dose increasing and was named MCF-7/DOX. Afterwards, wound healing and
      Transwell assays were performed to measure the migration and invasion
      capabilities of MCF-7/DOX cells, while cell propagation and apoptosis were
      determined by colony formation assay and flow cytometry analysis. Both western
      blotting and immunohistochemistry were conducted to examine the expression of
      proteins involved in PI3K/Akt signaling pathway. Nude mice xenograft model was
      constructed to further verify the effects of DOX and RES on breast neoplasm in
      vivo. RES restored DOX sensitivity in MCF-7/DOX cells, inhibiting biological
      functions of MCF-7/DOX cells and promoting cell apoptosis in vitro and impeding
      tumor growth in vivo. It was revealed by the mechanistic studies that MCF-7/DOX
      cells could regain the drug sensibility with RES treatment through inactivating
      the PI3K/Akt signal transduction pathway. RES could reverse DOX resistance in
      breast neoplasm cells and inhibited DOX-resistant breast cancer cell propagation
      and metastasis and facilitated cell apoptosis by modulating PI3K/Akt signaling
      pathway. (c) 2018 IUBMB Life, 70(6):491-500, 2018.

PMID- 29637743
TI  - Specific issues concerning the management of patients on the waiting list and
      after liver transplantation.
AB  - The present document is a second contribution collecting the recommendations of
      an expert panel of transplant hepatologists appointed by the Italian Association
      for the Study of the Liver (AISF) concerning the management of certain aspects of
      liver transplantation, including: the issue of prompt referral; the management of
      difficult candidates; malnutrition; living related liver transplants;
      hepatocellular carcinoma; and the role of direct acting antiviral agents before
      and after transplantation. The statements on each topic were approved by
      participants at the AISF Transplant Hepatology Expert Meeting organized by the
      Permanent Liver Transplant Commission in Mondello on 12-13 May 2017. They are
      graded according to the GRADE grading system.

PMID- 29637744
TI  - The group VIA calcium-independent phospholipase A2 and NFATc4 pathway mediates IL
      1beta-induced expression of chemokines CCL2 and CXCL10 in rat fibroblasts.
AB  - Chemokines are secreted proteins that regulate cell migration and are involved in
      inflammatory and immune responses. Here, we sought to define the functional
      crosstalk between the lipid signaling and chemokine signaling. We obtained
      evidence that the induction of some chemokines is regulated by group VIA calcium
      independent phospholipase A2 beta (iPLA2 beta) in IL-1beta-stimulated rat
      fibroblastic 3Y1 cells. Treatment of 3Y1 cells with IL-1beta elicited an
      increased release of chemotactic factor(s) for monocytic THP-1 cells into culture
      medium in a time-dependent manner. Inhibitor studies revealed that an
      intracellular PLA2 inhibitor, arachidonoyl trifluoromethyl ketone (AACOCF3 ), but
      not the cyclooxygenase inhibitor indomethacin, attenuated the release of
      chemotactic factor(s). The chemotactic activity was inactivated by treatment with
      either heat or proteinase K, suggesting this chemotactic factor(s) is a
      proteinaceous factor(s). We purified the chemotactic factor(s) from the
      conditioned medium of IL-1beta-stimulated 3Y1 cells using a heparin column and
      identified several chemokines, including CCL2 and CXCL10. The inducible
      expressions of CCL2 and CXCL10 were significantly attenuated by pretreatment with
      AACOCF3 . Gene silencing using siRNA revealed that the inductions of CCL2 and
      CXCL10 were attenuated by iPLA2 beta knockdown. Additionally, the transcriptional
      activation of nuclear factor of activated T-cell proteins (NFATs), but not
      nuclear factor-kappaB, by IL-1beta stimulation was markedly attenuated by the
      iPLA2 inhibitor bromoenol lactone, and NFATc4 knockdown markedly attenuated the
      IL-1beta-induced expression of both CCL2 and CXCL10. Collectively, these results
      indicated that iPLA2 beta plays roles in IL-1beta-induced chemokine expression,
      in part via NFATc4 signaling.

PMID- 29637745
TI  - Rubinstein-Taybi syndrome: New neuroradiological and neuropsychiatric insights
      from a multidisciplinary approach.
AB  - Rubinstein-Taybi syndrome is a rare, autosomal dominant, plurimalformative
      disorder that is clinically characterized by intellectual disability and a wide
      spectrum of congenital anomalies; facial dysmorphisms are typical, and broad
      thumbs and great toes are particularly distinctive. Its genetic basis is only
      partially known, with a detection rate of approximately 65-70%; specifically,
      microdeletions or mutations in the CREBBP or EP300 genes can be found. Much is
      known about its clinical features and health-care protocols, but some areas of
      clinical knowledge are currently unsolved. In particular, few efforts have been
      made until now to understand the variability in the neuropsychological and
      neurobehavioral profile and to deepen knowledge of the neuroradiological
      malformative pattern. Consequently, little is known about the possible genotype
      phenotype correlations of these issues. Here, we report clinical and genetic data
      from a cohort of 23 RSTS Italian patients. The most common features in brain
      magnetic resonance imaging (MRI) were dysmorphic aspects of the corpus callosum
      (73.6%) with or without minor dysmorphisms of cerebellar vermis, periventricular
      posterior white matter hyperintensity, and other less common anomalies. The most
      interesting feature on the whole spine MRI scans was the tendency for a low-lying
      conus medullaris without terminal filum thickening. These data will help to
      improve neuropsychiatric and neuroradiological knowledge and highlight specific
      genotype-phenotype correlations.

PMID- 29637746
TI  - Authors' Response to "Mutations in COL1A1 Gene Change Dentin Nanostructure: A
      Response".

PMID- 29637747
TI  - Albendazole and Praziquantel: Review and Safety Monitoring in Korea.
AB  - Albendazole (ADZ) and praziquantel (PZQT) have been used as anthelmintics for
      over 30 years. Worldwide, hundreds of millions tablets are administered to people
      and livestock every year. ADZ is poorly orally absorbed (<5%), and its uptake is
      enhanced by high-fat meals, while PZQT is well absorbed (>75%) and uptake is
      enhanced by carbohydrate-rich meals. Both ADZ and PZQT are safe, but not
      recommended for children <2 years or for women in the first trimester of
      pregnancy. Serious adverse events occur following high dose and prolonged
      administration of these drugs for treatment of echinococcosis or
      neurocysticercosis, especially in patients with poor liver function. The adverse
      events may be induced by the drugs, or by the dead worms themselves. The Korea
      Institute of Drug Safety & Risk Management monitors drug-related adverse events
      in Korea, and its database included 256 probable or possible ADZ-associated
      events and 108 PZQT-associated events between 2006 and 2015. Such low incidence
      rates in Korea are due to the low single dose treatments of ADZ, and the short
      term use of PZQT. The number of serious adverse events due to drug interaction
      induced by ADZ and PZQT were six and two, respectively. We conclude that ADZ and
      PZQT are generally safe drugs, but they must be used with caution in people with
      poor liver function or those being comedicated for gastroesophageal reflux
      disease.

PMID- 29637748
TI  - Microbiology and Antimicrobial Therapy for Diabetic Foot Infections.
AB  - In addition to being the prime factor associated with amputation, diabetic foot
      infections (DFIs) are associated with major morbidity, increasing mortality, and
      reduced quality of life. The choice of appropriate antibiotics is very important
      in order to reduce treatment failure, antimicrobial resistance, adverse events,
      and costs. We reviewed articles on microbiology and antimicrobial therapy and
      discuss antibiotic selection in Korean patients with DFIs. Similar to Western
      countries, Staphylococcus aureus is the most common pathogen, with Streptococcus,
      Enterococcus, Enterobacteriaceae and Pseudomonas also prevalent in Korea. It is
      recommended that antibiotics are not prescribed for clinically uninfected wounds
      and that empirical antibiotics be selected based on the clinical features,
      disease severity, and local antimicrobial resistance patterns. Narrow-spectrum
      oral antibiotics can be administered for mild infections and broad-spectrum
      parenteral antibiotics should be administered for some moderate and severe
      infections. In cases with risk factors for methicillin-resistant S. aureus or
      Pseudomonas, empirical antibiotics to cover each pathogen should be considered.
      The Health Insurance Review and Assessment Service standards should also be
      considered when choosing empirical antibiotics. In Korea, nationwide studies need
      to be conducted and DFI guidelines should be developed.

PMID- 29637749
TI  - Epidemiology, Microbiological and Clinical Features, Treatment, and Outcomes of
      Infective Endocarditis in Crete, Greece.
AB  - BACKGROUND: This study aimed to evaluate the epidemiology, clinical and
      microbiological features, treatment, and outcomes of infective endocarditis (IE)
      on the island of Crete, a region with high levels of antimicrobial resistance.
      MATERIALS AND METHODS: Medical records of all hospitalized patients diagnosed
      with IE at the University Hospital of Heraklion, Crete, Greece, from 1995 to
      2015, were retrospectively reviewed. Patients who met the modified Duke's
      criteria for definite or possible IE were included. RESULTS: A total of 82 IE
      patients (median age 67 [range 21-86] years) were included. Most patients
      suffered from left-sided IE (94%), while most cases of infection occurred in
      native valves (53.6%). Systemic inflammatory response syndrome criteria were
      lacking in almost half of the patient population. The leading causative
      microorganism was Staphylococcus aureus, isolated in 24 cases (29%), followed by
      Streptococcus spp. in 15 (18%) and Enterococcus spp. in 12 (14.5%). A number of
      rare and difficult to treat microorganisms had been identified, such as Gemella
      morbillorum in four cases (4.5%), Streptococcus lugdunensis in two (2.5%) and
      Streptococcus pneumoniae in one (1%). One patient was serologically positive for
      Coxiella burnetii (1%). All patients received empirical antimicrobial treatment,
      proven appropriate in 39 blood culture-positive patients (56.5%). Thirteen (16%)
      patients were classified as culture negative. Seven patients (8.5%) were
      surgically treated. In-hospital death occurred in 9 patients (11%). CONCLUSION:
      Changes in IE profile requires continuous epidemiological updates. Staphylococcus
      and Streptococcus spp. remain the most common etiologic agents. However, the
      presence of uncommon and/or difficult to treat pathogens raise concerns on the
      appropriate prophylaxis as well as empirical treatment.

PMID- 29637750
TI  - Genotypic Diversity of Multidrug Resistant Shigella species from Iran.
AB  - BACKGROUND: In many developing countries, shigellosis is endemic and also occurs
      in epidemics and treatment of multidrug-resistant (MDR) isolates are important.
      The aims of this study were to determine the antimicrobial susceptibility,
      prevalence of class 1 and 2 integrons and the clonal relatedness of isolates.
      MATERIALS AND METHODS: Antimicrobial susceptibility tests were performed by disc
      diffusion method. Polymerase chain reaction (PCR)-sequencing technique was
      employed for detection and characterization of integrons. The genetic relatedness
      was evaluated by using enterobacterial repetitive intergenic consensus (ERIC)
      PCR. RESULTS: There was a high percentage of resistance to trimethoprim
      sulfamethoxazole (TMP/SMX) (93.7%), ampicillin (AMP) (87.3%), streptomycin (STR)
      (84.5%) and tetracycline (TET) (78.9%). Multidrug resistant phenotype was seen in
      95.1% of total isolates. Most common MDR profile was TMP/SMX/STR/AMP resistant
      pattern. Among the 142 Shigella spp. analyzed in this study, 28 isolates were
      positive for class 1 integron with two types of gene cassette arrays
      (dfrA17/aadA5 = 31.7% and dfrA7 = 3.8%). The class 2 integron was more frequently
      detected among the isolates (94.7%) with dfrA1/sat1/aadA1 (69.4%) and dfrA1/sat1
      (30.6%) gene cassettes. ERIC-PCR results showed 6, 5, 4 and 3 main genotypes
      among S. flexneri, S. sonnei, S. boydii and S. dysenteriae isolates,
      respectively. CONCLUSIONS: Our findings revealed that multidrug resistant
      Shigella species with high prevalence of class 2 integron were very common in
      Iran. In addition, ERIC-PCR patterns showed limited variety of clones are
      responsible for shigellosis in the region of the study.

PMID- 29637751
TI  - Investigation of Scarlet Fever Outbreak in a Kindergarten.
AB  - BACKGROUND: Scarlet fever is caused by a group A streptococcal (GAS) infection.
      On April 3, 2017, an outbreak among children in a kindergarten was reported to
      the local health department. An epidemiologic investigation was conducted to
      identify the possible transmission route of this outbreak and to recommend
      appropriate control measures. MATERIALS AND METHODS: A retrospective cohort study
      was conducted using questionnaires including age, sex, the classroom attended at
      a kindergarten, and date and type of symptoms developed. A case-patient is
      defined as a child having sore throat, fever, skin rash, or strawberry tongue
      with or without laboratory confirmation of GAS infection between March 28 and
      April 28, 2017. RESULTS: The index case-patients developed symptoms on March 28,
      2017, and this outbreak persisted over a period of 16 days. The outbreak affected
      21 out of 158 children (13.3%) in the kindergarten, with the mean age of 4.2
      (range 3-5) years; 12 (57.1%) of them were boys. The common symptoms reported
      were fever (71.4%), sore throat (71.4%), reddened tonsil (57.1%), and skin rash
      (52.4%). The epidemiologic analysis showed that children attending one of the
      classrooms in the kindergarten were 14.12 times affected than the other
      classrooms (relative risk, 14.12; 95% confidence interval, 4.99-33.93; P <0.01).
      All case-patients were recommended to stay away from the kindergarten and its
      social activities for >24 hours after starting appropriate antibiotic treatment,
      and all the children in the kindergarten were instructed to keep strict personal
      hygiene practices. CONCLUSION: Our results suggest that the outbreak likely
      affected from the index case-patients who attended to one of the classrooms in
      the kindergarten. This highlights the importance of immediate notification of
      outbreak to prevent large number of patients.

PMID- 29637752
TI  - Outcome in Patients with Fever of Unknown Origin whose 18Fluoro-Deoxyglucose
      Positron Emission Tomography/Computerized Tomography Finding is Non-Diagnostic.
AB  - Prognosis has not been known for patients with fever of unknown origin (FUO)
      whose 18fluoro-deoxyglucose (18F-FDG) positron emission tomography/computerized
      tomography (PET/CT) finding is non-diagnostic. A total of eight patients with FUO
      that underwent 18F-FDG PET/CT were retrospectively identified January 2016 - June
      2017 in a tertiary hospital in Korea. Of these, two patients were diagnosed with
      microscopic polyangitis and Kikuchi's disease and one patient was transferred to
      another hospital. Of five patients whose diagnoses were not confirmed, four
      patients received non-steroidal anti-inflammatory drug and/or low dose steroid
      and symptoms disappeared. Our study suggests that outcome of patients with FUO
      whose 18F-FDG PET/CT finding is non-diagnostic would be favorable.

PMID- 29637753
TI  - Is Taking Blood Cultures Indicated in Acute Pyelonephritis Patients Who Have Used
      Antibiotics before Presentation?

PMID- 29637754
TI  - Reply: Is Taking Blood Cultures Indicated in Acute Pyelonephritis Patients Who
      Have Used Antibiotics before Presentation?

PMID- 29637755
TI  - A Case of Jejunal Intussusception caused by Burkitt Lymphoma in an Acquired
      Immunodeficiency Syndrome Patient.
AB  - Non-Hodgkin's lymphoma of B-cell type is the second most common neoplasm after
      Kaposi's sarcoma among patients with human immunodeficiency virus infection. Most
      non-Hodgkin's lymphoma cases that are associated with acquired immunodeficiency
      syndrome (AIDS) involve extranodal sites, especially the digestive tract and the
      central nervous system. We report a case of multiple jejunal intussusception
      caused by Burkitt lymphoma in a 42-year-old AIDS patient. Upper gastrointestinal
      endoscopy and surgical biopsy were performed and a complete diagnostic study
      including histological and immunohistochemical analyses showed Burkitt lymphoma.

PMID- 29637756
TI  - A Case of Scrub Typhus complicated with a Splenic Infarction.
AB  - We present a patient with scrub typhus complicated with a splenic infarction. A
      40-year-old man visited the emergency medical center complaining of fever for the
      previous week. He had no past medical history, but reported engaging in outdoor
      activities. Examination revealed a maculopapular rash on his trunk and an eschar
      on his epigastrium. Abdominal computed tomography was performed to examine the
      cause of the tenderness on the left upper quadrant of his abdomen, which revealed
      a splenic infarct. The patient was diagnosed with scrub typhus based on the
      results of blood polymerase chain reaction testing, and genetic sequencing
      confirmed the presence of Orientia tsutsugamushi Boryong. His symptoms improved
      following doxycycline treatment.

PMID- 29637757
TI  - Disseminated Invasive Mycobacterium marinum Infection Involving the Lung of a
      Patient with Diabetes Mellitus.
AB  - Mycobacterium marinum infection in humans occurs mainly as a granulomatous
      infection after exposure of traumatized skin to contaminated water. It is usually
      confined to the skin and soft tissue. Disseminated disease involving other organs
      rarely occurs in immunocompetent patients. Here, we report a case of disseminated
      M. marinum infection involving not only the cutaneous tissue, but also the lung
      of a male patient with uncontrolled diabetes and a previous history of steroid
      injection who was employed by a deep-water fishery.

PMID- 29637758
TI  - Outbreak Investigation of Scarlet Fever in a Kindergarten.

PMID- 29637760
TI  - Noninvasive measurement of glucose concentration on human fingertip by optical
      coherence tomography.
AB  - A method is proposed for determining the glucose concentration on the human
      fingertip by extracting two optical parameters, namely the optical rotation angle
      and the depolarization index, using a Mueller optical coherence tomography
      technique and a genetic algorithm. The feasibility of the proposed method is
      demonstrated by measuring the optical rotation angle and depolarization index of
      aqueous glucose solutions with low and high scattering, respectively. It is shown
      that for both solutions, the optical rotation angle and depolarization index vary
      approximately linearly with the glucose concentration. As a result, the ability
      of the proposed method to obtain the glucose concentration by means of just two
      optical parameters is confirmed. The practical applicability of the proposed
      technique is demonstrated by measuring the optical rotation angle and
      depolarization index on the human fingertip of healthy volunteers under various
      glucose conditions.

PMID- 29637761
TI  - Controllable Formation of Monodisperse Polymer Microbubbles as Ultrasound
      Contrast Agents.
AB  - Microbubbles have been widely used as ultrasound contrast agents in clinical
      diagnosis and hold great potential for ultrasound-mediated therapy. However,
      polydispersed population and short half-life time (<10 min) of the microbubbles
      still limit their applications in imaging and therapy. To tackle these problems,
      we develop a microfluidic flow-focusing approach to produce monodisperse
      microbubbles stabilized by Poly(lactic-co-glycolic acid) (PLGA) as the polymer
      shell. The size of PLGA microbubbles can be tightly controlled from ~600 nm to ~7
      MUm with a coefficient of variation less than 4% in size distribution for
      ensuring highly homogeneous echogenic behavior of PLGA polymer microbubbles in
      ultrasound fields. Both in vitro and in vivo experiments showed that the
      monodisperse PLGA microbubbles had excellent echogenicity and elongated
      sonographic duration time (>3 times) for ultrasound imaging in comparison with
      the commercial lipid microbubbles.

PMID- 29637762
TI  - Green and Rational Design of 3D Layer-by-Layer MnO x Hierarchically Mesoporous
      Microcuboids from MOF Templates for High-Rate and Long-Life Li-Ion Batteries.
AB  - Rational design and delicate control on the textural properties of metal-oxide
      materials for diverse structure-dependent applications still remain formidable
      challenges. Here, we present an eco-friendly and facile approach to smartly
      fabricate three-dimensional (3D) layer-by-layer manganese oxide (MnO x)
      hierarchical mesoporous microcuboids from a Mn-MOF-74-based template, using a one
      step solution-phase reaction scheme at room temperature. Through the controlled
      exchange of metal-organic framework (MOF) ligand with OH- in alkaline aqueous
      solution and in situ oxidation of manganese hydroxide intermediate, the Mn-MOF-74
      template/precursor was readily converted to Mn3O4 or delta-MnO2 counterpart
      consisting of primary nanoparticle and nanosheet building blocks, respectively,
      with well-retained morphology. By X-ray diffraction, transmission electron
      microscopy (TEM), scanning electron microscopy, high-resolution TEM, N2
      adsorption-desorption analysis and other techniques, their crystal structure,
      detailed morphology, and microstructure features were unambiguously revealed.
      Specifically, their electrochemical Li-ion insertion/extraction properties were
      well evaluated, and it turns out that these unique 3D microcuboids could achieve
      a sustained superior lithium-storage performance especially at high rates
      benefited from the well-orchestrated structural characteristics (Mn3O4
      microcuboids: 890.7, 767.4, 560.1, and 437.1 mAh g-1 after 400 cycles at 0.2,
      0.5, 1, and 2 A g-1, respectively; delta-MnO2 microcuboids: 991.5, 660.8, 504.4,
      and 362.1 mAh g-1 after 400 cycles at 0.2, 0.5, 1, and 2 A g-1, respectively). To
      our knowledge, this is the most durable high-rate capability as well as the
      highest reversible capacity ever reported for pure MnO x anodes, which even
      surpass most of their hybrids. This facile, green, and economical strategy renews
      the traditional MOF-derived synthesis for highly tailorable functional materials
      and opens up new opportunities for metal-oxide electrodes with high performance.

PMID- 29637759
TI  - Clinical Practice Guidelines for the Antibiotic Treatment of Community-Acquired
      Urinary Tract Infections.
AB  - Urinary tract infections (UTIs) are infectious diseases that commonly occur in
      communities. Although several international guidelines for the management of UTIs
      have been available, clinical characteristics, etiology and antimicrobial
      susceptibility patterns may differ from country to country. This work represents
      an update of the 2011 Korean guideline for UTIs. The current guideline was
      developed by the update and adaptation method. This clinical practice guideline
      provides recommendations for the diagnosis and management of UTIs, including
      asymptomatic bacteriuria, acute uncomplicated cystitis, acute uncomplicated
      pyelonephritis, complicated pyelonephritis related to urinary tract obstruction,
      and acute bacterial prostatitis. This guideline targets community-acquired UTIs
      occurring among adult patients. Healthcare-associated UTIs, catheter-associated
      UTIs, and infections in immunocompromised patients were not included in this
      guideline.

PMID- 29637763
TI  - Metal-Organic Frameworks-Derived Co2P@N-C@rGO with Dual Protection Layers for
      Improved Sodium Storage.
AB  - The Co2P nanoparticles hybridized with unique N-doping carbon matrices have been
      successfully designed employing ZIF-67 as the precursor via a facile two-step
      procedure. The Co2P nanostructures are shielded with reduced graphene oxide (rGO)
      to enhance electrical conductivity and mitigate volume expansion/shrinkage during
      sodium storage. As anode materials for sodium-ion batteries (SIBs), the novel
      architectures of Co2P@N-C@rGO exhibited excellent sodium storage performance with
      a high reversible capacity of 225 mA h g-1 at 50 mA g-1 after 100 cycles. Our
      study demonstrates the significant potential of Co2P@N-C@rGO as anode materials
      for SIBs.

PMID- 29637764
TI  - Surface-Anchored Metal-Organic Framework-Cotton Material for Tunable
      Antibacterial Copper Delivery.
AB  - In the present study, a new copper metal-organic framework (MOF)-cotton material
      was strategically fabricated to exploit its antibacterial properties for
      postsynthetic modification (PSM) to introduce a free amine to tune the
      physicochemical properties of the material. A modified methodology for
      carboxymethylation of natural cotton was utilized to enhance the number of
      nucleation sites for the MOF growth. Subsequently, MOF Cu3(NH2BTC)2 was
      synthesized into a homogenous surface-supported film via a layer-by-layer dip
      coating process. The resultant materials contained uniformly distributed 1 MUm *
      1 MUm octahedral MOF crystals around each carboxymethylated fiber. Importantly,
      the accessible free amine of the MOF ligand allowed for the PSM of the MOF-cotton
      surface with valeric anhydride, yielding 23.5 +/- 2.2% modified. The Cu2+ ion
      releasing performance of the materials was probed under biological conditions per
      submersion in complex media at 37  degrees C. Indeed, PSM induces a change in the
      copper flux of the material over the first 6 h. The materials continue to slowly
      release Cu2+ ions beyond 24 h tested at a flux of 0.22 +/- 0.003 MUmol.cm-2.h-1
      with the unmodified MOF-cotton and at 0.25 +/- 0.004 MUmol.cm-2.h-1 with the
      modified MOF-cotton. The antibacterial activity of the material was explored
      using Escherichia coli by testing the planktonic and attached bacteria under a
      variety of conditions. MOF-cotton materials elicit antibacterial effects,
      yielding a 4-log reduction or greater, after 24 h of exposure. Additionally, the
      MOF-cotton materials inhibit the attachment of bacteria, under both dry and wet
      conditions. A material of this type would be ideal for clothing, bandages, and
      other textile applications. As such, this work serves as a precedence toward
      developing uniform, tunable MOF-composite textile materials that can kill
      bacteria and prevent the attachment of bacteria to the surface.

PMID- 29637765
TI  - N,P-Doped Molybdenum Carbide Nanofibers for Efficient Hydrogen Production.
AB  - Molybdenum (Mo) carbide-based electrocatalysts are considered promising
      candidates to replace Pt-based materials toward the hydrogen evolution reaction
      (HER). Among different crystal phases of Mo carbides, although Mo2C exhibits the
      highest catalytic performance, the activity is still restricted by the strong Mo
      H bonding. To weaken the strong Mo-H bonding, creating abundant Mo2C/MoC
      interfaces and/or doping a proper amount of electron-rich (such as N and P)
      dopants into the Mo2C crystal lattice are effective because of the electron
      transfer from Mo to surrounding C in carbides and/or N/P dopants. In addition, Mo
      carbides with well-defined nanostructures, such as one-dimensional nanostructure,
      are desirable to achieve abundant catalytic active sites. Herein, well-defined
      N,P-codoped Mo2C/MoC nanofibers (N,P-Mo xC NF) were prepared by pyrolysis of
      phosphomolybdic ([PMo12O40]3-, PMo12) acid-doped polyaniline nanofibers at 900 
      degrees C under an Ar atmosphere, in which the hybrid polymeric precursor was
      synthesized via a facile interfacial polymerization method. The experimental
      results indicate that the judicious choice of pyrolysis temperature is essential
      for creating abundant Mo2C/MoC interfaces and regulating the N,P-doping level in
      both Mo carbides and carbon matrixes, which leads to optimized electronic
      properties for accelerating HER kinetics. As a result, N,P-Mo xC NF exhibits
      excellent HER catalytic activity in both acidic and alkaline media. It requires
      an overpotential of only 107 and 135 mV to reach a current density of 10 mA cm-2
      in 0.5 M H2SO4 and 1 M KOH, respectively, which is comparable and even superior
      to the best of Mo carbide-based electrocatalysts and other noble metal-free
      electrocatalysts.

PMID- 29637766
TI  - High-Performance Dye-Sensitized Solar Cells Based on Colloid-Solution Deposition
      Planarized Fluorine-Doped Tin Oxide Substrates.
AB  - The transmittance and conductivity of fluorine-doped tin oxide (FTO) conductive
      glasses are the critical factors limiting the performance of dye-sensitized solar
      cells (DSSCs). Here, the transmittance and conductivity of commercial FTO glasses
      were improved via a colloid-solution deposition planarization (CSDP) process. The
      process includes two steps. First, the FTO nanocrystal colloid was deposited on
      the FTO glasses by spin-coating. Secondly, the coated glasses were treated by FTO
      precursor solution. Compared to the bare FTO glasses, the modified FTO glasses by
      the CSDP process achieved 4% increase in transmittance (at 550 nm) and 11%
      decrease in sheet resistance, respectively. In addition, the modified FTO glasses
      can reduce the aggregation of Pt nanoparticles and improve the electrocatalytic
      activity of Pt counter electrodes. When the modified FTO glasses were used to
      assemble DSSCs, the cells got a photoelectric conversion efficiency as high as
      9.37%. In contrast, the efficiency of reference cells using bare FTO substrates
      was about 8.24%.

PMID- 29637767
TI  - Influence of Shell Thickness on the Performance of NiO-Based All-Inorganic
      Quantum Dot Light-Emitting Diodes.
AB  - The effect of shell thickness on the performance of all-inorganic quantum dot
      light-emitting diodes (QLEDs) is explored by employing a series of green quantum
      dots (QDs) (Zn xCd1- xSe/ZnS core/shell QDs with different ZnS shell thicknesses)
      as the emitters. ZnO nanoparticles and sol-gel NiO are employed as the electron
      and hole transport materials, respectively. Time-resolved and steady-state
      photoluminescence results indicate that positive charging processes might occur
      for the QDs deposited on NiO, which results in emission quenching of QDs and poor
      device performance. The thick shell outside the core in QDs not only largely
      suppresses the QD emission quenching but also effectively preserves the excitons
      in QDs from dissociation of electron-hole pairs when they are subjected to an
      electric field. The peak efficiency of 4.2 cd/A and maximum luminance of 4205
      cd/m2 are achieved for the device based on QDs with the thickest shells (~4.2
      nm). We anticipate that these results will spur progress toward the design and
      realization of efficient all-inorganic QLEDs as a platform for the QD-based full
      colored displays.

PMID- 29637768
TI  - Chelate-Pb Intermediate Engineering for High-Efficiency Perovskite Solar Cells.
AB  - Crystallization quality and grain size are key factors in fabricating high
      performance planar-type perovskite photovoltaics. Herein, we used 1,8
      octanedithiol as an effective additive in the [HC(NH2)2]0.95Cs0.05PbI3
      (FA0.95Cs0.05PbI3) solution to improve the FA0.95Cs0.05PbI3 film quality via
      solution processing. 1,8-Octanedithiol would coordinate with lead to form the
      chelate-Pb compound, leading to smaller Gibbs free energy during the perovskite
      crystallization process, facilitating formation of high-quality perovskite films
      with larger grains, smoother surfaces, lower electron trap densities, and longer
      carrier lifetimes compared to the nonadditive ones. As a result, the champion
      efficiency for devices with 3% 1,8-octanedithiol-doped FA0.95Cs0.05PbI3 is raised
      to 19.36% from 18.39% of a device without the additive. The new technique is a
      promising way to fabricate perovskite photovoltaics with high performance.

PMID- 29637769
TI  - Fabrication of a Microfluidic Flame Atomic Emission Spectrometer: a Flame-on-a
      Chip.
AB  - This work demonstrates for the first time the fabrication of a microfluidic flame
      atomic emission spectrometer (FAES), which incorporates a microburner and flame
      (flame-on-a-chip). An essential part of the device is a thermospray system
      applied for effective sample introduction, which is more easily miniaturizable
      and integrable than the conventional nebulization methods. The merits and
      limitations of the microfluidic flame atomic emission device were demonstrated
      and discussed. Using a commercial cigarette lighter including butane gas, the
      flame temperature made the analysis of the most easily excitable alkali metals
      possible. The calibration diagrams for Li, Na, and K showed proper linearity in
      the range of 5-100 mg/L. The analytical applicability of the microfluidic FAES
      device was tested by analyzing various real samples.

PMID- 29637770
TI  - Rediscovering Acetate Metabolism: Its Potential Sources and Utilization for
      Biobased Transformation into Value-Added Chemicals.
AB  - One of the great advantages of microbial fermentation is the capacity to convert
      various carbon compounds into value-added chemicals. In this regard, there have
      been many efforts to engineer microorganisms to facilitate utilization of
      abundant carbon sources. Recently, the potential of acetate as a feedstock has
      been discovered; efforts have been made to produce various biochemicals from
      acetate based on understanding of its metabolism. In this review, we discuss the
      potential sources of acetate and summarized the recent progress to improve
      acetate utilization with microorganisms. Furthermore, we also describe
      representative studies that engineered microorganisms for the production of
      biochemicals from acetate.

PMID- 29637771
TI  - The Structure of the Protonated Serine Octamer.
AB  - The amino acid serine has long been known to form a protonated "magic-number"
      cluster containing eight monomer units that shows an unusually high abundance in
      mass spectra and has a remarkable homochiral preference. Despite many
      experimental and theoretical studies, there is no consensus on a Ser8H+ structure
      that is in agreement with all experimental observations. Here, we present the
      structure of Ser8H+ determined by a combination of infrared spectroscopy and ab
      initio molecular dynamics simulations. The three-dimensional structure that we
      determine is ~25 kcal mol-1 more stable than the previous most stable published
      structure and explains both the homochiral preference and the experimentally
      observed facile replacement of two serine units.

PMID- 29637772
TI  - The Gelsolin Pathogenic D187N Mutant Exhibits Altered Conformational Stability
      and Forms Amyloidogenic Oligomers.
AB  - Gelsolin is an actin-severing protein that attains an open functional
      conformation in the presence of Ca2+ or low pH. Mutations (D187N/Y) in the second
      domain of gelsolin trigger the proteolytic pathway producing amyloidogenic
      fragments that form the pathological hallmark of gelsolin amyloidosis and lattice
      corneal dystrophy type 2 (LCD2). Here, we show that the D187N mutant gelsolin in
      a Ca2+ depleted, low pH-activated, open conformation could assemble into
      amyloidogenic oligomers without necessarily undergoing the specific proteolytic
      step. Although both wild-type (WT) and mutant proteins exhibit closely
      overlapping globular shapes at physiological conditions, the latter exhibits
      subjugated actin depolymerization, loss of thermodynamic stability, and folding
      cooperativity. Mutant gelsolin displayed aberrant conformational unwinding and
      formed structural conformers with high associative properties at low pH
      conditions. A SAXS intensity profile and Guinier analysis of these conformers
      showed the formation of unusual, higher order aggregates. Extended incubation at
      low pH resulted in the formation of thioflavin T and Congo red positive, beta
      sheet rich aggregates with a fibrillar, amyloid-like morphology visible under
      electron and atomic force microscopy. Mass spectrometric analysis of
      disaggregated end-stage fibrils displayed peptide fragments encompassing the
      entire protein sequence, indicating the involvement of full length mutant
      gelsolin in fibril formation. Atomistic and REMD simulations indicated a larger
      increase in solvent accessibility and loss of fold architecture in mutant
      gelsolin at low pH as compared to WT gelsolin. Our findings support the existence
      of a secondary oligomerization-dependent aggregation pathway associated with
      gelsolin amyloidosis and can pave the way for better therapeutic strategies.

PMID- 29637773
TI  - Activatable Fluorescence Probe via Self-Immolative Intramolecular Cyclization for
      Histone Deacetylase Imaging in Live Cells and Tissues.
AB  - Histone deacetylases (HDACs) play essential roles in transcription regulation and
      are valuable theranostic targets. However, there are no activatable fluorescent
      probes for imaging of HDAC activity in live cells. Here, we develop for the first
      time a novel activatable two-photon fluorescence probe that enables in situ
      imaging of HDAC activity in living cells and tissues. The probe is designed by
      conjugating an acetyl-lysine mimic substrate to a masked aldehyde-containing
      fluorophore via a cyanoester linker. Upon deacetylation by HDAC, the probe
      undergoes a rapid self-immolative intramolecular cyclization reaction, producing
      a cyanohydrin intermediate that is spontaneously rapidly decomposed into the
      highly fluorescent aldehyde-containing two-photon fluorophore. The probe is shown
      to exhibit high sensitivity, high specificity, and fast response for HDAC
      detection in vitro. Imaging studies reveal that the probe is able to directly
      visualize and monitor HDAC activity in living cells. Moreover, the probe is
      demonstrated to have the capability of two-photon imaging of HDAC activity in
      deep tissue slices up to 130 MUm. This activatable fluorescent probe affords a
      useful tool for evaluating HDAC activity and screening HDAC-targeting drugs in
      both live cell and tissue assays.

PMID- 29637774
TI  - Transformation, Conjugation, and Sequestration Following the Uptake of
      Triclocarban by Jalapeno Pepper Plants.
AB  - Plant uptake and metabolism of emerging organic contaminants, such as personal
      care products, pose potential risks to human health. In this study, jalapeno
      pepper ( Capsicum annuum) plants cultured in hydroponic media were exposed to
      both 14C-labeled and unlabeled triclocarban (TCC) to investigate the
      accumulation, distribution, and metabolism of TCC following plant uptake. The
      results revealed that TCC was detected in all plant tissues; after 12 weeks, the
      TCC concentrations in root, stem, leaf, and fruit tissues were 19.74 +/- 2.26,
      0.26 +/- 0.04, 0.11 +/- 0.01, and 0.03 +/- 0.01 mg/kg dry weight, respectively.
      More importantly, a substantial portion of the TCC taken up by plants was
      metabolized, especially in the stems, leaves, and fruits. Hydroxylated TCC (e.g.,
      2'-OH TCC and 6-OH TCC) and glycosylated OH-TCC were the main phase I and phase
      II metabolites in plant tissues, respectively. Bound (or nonextractable) residues
      of TCC accounted for approximately 44.6, 85.6, 69.0, and 47.5% of all TCC species
      that accumulated in roots, stems, leaves, and fruits, respectively. The
      concentrations of TCC metabolites were more than 20 times greater than the
      concentrations of TCC in the above-ground tissues of the jalapeno pepper plants
      after 12 weeks; crucially, approximately 95.6% of the TCC was present as
      metabolites in the fruits. Consequently, human exposure to TCC through the
      consumption of pepper fruits is expected to be substantially higher when
      phytometabolism is considered.

PMID- 29637775
TI  - Facile Fabrication of a Modular "Catch and Release" Hydrogel Interface:
      Harnessing Thiol-Disulfide Exchange for Reversible Protein Capture and Cell
      Attachment.
AB  - Surfaces engineered to "specifically capture" and "release on demand" analytes
      ranging from biomolecules to cells find niche applications in areas such as
      diagnostics and detection. Utilization of a disulfide-based linker as a building
      block allows fabrication of a novel hydrogel-based platform that incorporates a
      "catch and release" attribute. Hydrogels incorporating pyridyl disulfide groups
      as thiol-reactive handles were prepared by photopolymerization in the presence of
      a poly(ethylene glycol) (PEG)-based cross-linker. A range of bulk and
      micropatterned hydrogels with varying amounts of the reactive group were prepared
      using PEG-based monomers with different chain lengths. Thiol-containing molecules
      were conjugated to these hydrogels through the thiol-disulfide exchange reaction
      under ambient conditions with high efficiencies, as determined by UV-vis
      spectroscopy. Facile conjugation of a thiol-containing fluorescent dye, namely
      4,4-difluoro-1,3,5,7-tetramethyl-8-[(10-mercapto)]-4-bora-3 a,4 a-diaza- s
      indacene, was demonstrated, followed by its effective cleavage in the presence of
      dithiothreitol (DTT), a thiol-containing disulfide-reducing agent. Conjugation of
      a biotin-containing ligand onto the hydrogels allowed specific binding of protein
      extravidin when exposed to a mixture of extravidin and bovine serum albumin. The
      bound protein could be released from the hydrogel by simple exposure to a DTT
      solution. Likewise, hydrogels modified with a cell-adhesive peptide unit
      containing the RGD sequence acted as favorable substrates for cellular
      attachment. Incubation of these cell-attached hydrogel surfaces in a DTT
      containing solution leads to facile detachment of cells from the surfaces, while
      retaining a high level of cell viability. It can be envisioned that the benign
      nature of these hydrogels, their facile fabrication, and modular
      functionalization will make them attractive platforms for many applications.

PMID- 29637776
TI  - Design of Nanofiber Coatings for Mitigation of Microbial Adhesion: Modeling and
      Application to Medical Catheters.
AB  - Surface-associated microbial communities, known as biofilms, pose significant
      challenges in clinical and industrial settings. Micro-/nanoscale substratum
      surface features have been shown to disrupt firm adhesion of planktonic microbes
      to surfaces, thereby interfering with the earliest stage of biofilm formation.
      However, the role of geometry and size of surface features in microbial retention
      is not completely understood. In this study, we developed a biophysical model
      that describes the changes in the total free energy (adhesion energy and
      stretching energy) of an adherent Candida albicans cell on nanofiber-coated
      surfaces as a function of the geometry (i.e., diameter) and configuration (i.e.,
      interfiber spacing) of the surface features (i.e., nanofibers). We then
      introduced a new nondimensional parameter, Pi, to represent the ratio of cell
      rigidity to cell-substratum interfacial energy. We show that the total free
      energy is a strong function of topographical feature size at higher Pi and lower
      spacing values. To confirm our biophysical model predictions, we performed 24 h
      dynamic retention assays and quantified cell attachment number density on
      surfaces coated with highly ordered polystyrene nanofibers. We show that the
      total free energy of a single adherent cell on a patterned surface is a key
      determinant of microbial retention on that surface. The cell attachment density
      trend closely correlates with the predictions based on the adherent single-cell
      total energy. The nanofiber coating design (1.2 MUm diameter, 2 MUm spacing) that
      maximized the total energy of the adherent cell resulted in the lowest microbial
      retention. We further demonstrate the utility of our biophysical model by showing
      close correlation between the computed single-cell total free energy and biofilm
      nucleation on fiber-coated urinary and central venous catheters of different
      materials. This biophysical model could offer a powerful new paradigm in ab
      initio design of patterned surfaces for controlled biofilm growth for medical
      applications and beyond.

PMID- 29637777
TI  - Chemically Regulated ROS Generation from Gold Nanoparticles for Enzyme-Free
      Electrochemiluminescent Immunosensing.
AB  - In the present work, we report on an enzyme-free electrochemiluminescent (ECL)
      immunosensing scheme utilizing the catalytic generation of reactive oxygen
      species (ROS) from gold nanoparticles (AuNPs) (diameter >=5 nm) dispersed in
      aqueous solutions of trishydroxymethylaminomethane (Tris). First, to examine this
      catalytic pathway in detail, the effects of various factors such as the AuNP size
      and concentration, dispersant type and concentration, and dissolved oxygen were
      investigated using the electrochemiluminescence (ECL) of luminol. It was found
      that the catalytic generation of ROS from AuNPs can be regulated chemically by
      altering conditions such as the type, concentration, and pH of the solution that
      the AuNPs are dispersed in. Under the best conditions studied in this work, the
      AuNPs displayed high catalytic activity toward ROS generation, with an estimated
      apparent turnover number per AuNP of 0.1 s-1, comparable to those of several
      common peroxide-producing enzymes. Following these studies, this phenomenon was
      applied to develop a one-step enzyme-free ECL immunosensor based on sandwiching
      the target analyte using antibody-conjugated magnetic beads (MB) and AuNPs. Using
      IgA as a model analyte, the developed immunosensor was able to detect the target
      in the range of 1 ng/mL to 10 MUg/mL, with the lower detection limit being
      comparable to those of commercial assays for the same target. Altering the
      antibodies used to modify the MB and AuNPs could further improve the detection
      limit as well as expand the applicability of this immunoassay to the detection of
      other analytes.

PMID- 29637778
TI  - Strain-Driven Nanoscale Phase Competition near the Antipolar-Nonpolar Phase
      Boundary in Bi0.7La0.3FeO3 Thin Films.
AB  - Complex-oxide materials tuned to be near phase boundaries via
      chemistry/composition, temperature, pressure, etc. are known to exhibit large
      susceptibilities. Here, we observe a strain-driven nanoscale phase competition in
      epitaxially constrained Bi0.7La0.3FeO3 thin films near the antipolar-nonpolar
      phase boundary and explore the evolution of the structural, dielectric,
      (anti)ferroelectric, and magnetic properties with strain. We find that
      compressive and tensile strains can stabilize an antipolar PbZrO3-like Pbam phase
      and a nonpolar Pnma orthorhombic phase, respectively. Heterostructures grown with
      little to no strain exhibit a self-assembled nanoscale mixture of the two
      orthorhombic phases, wherein the relative fraction of each phase can be modified
      with film thickness. Subsequent investigation of the dielectric and
      (anti)ferroelectric properties reveals an electric-field-driven phase
      transformation from the nonpolar phase to the antipolar phase. X-ray linear
      dichroism reveals that the antiferromagnetic-spin axes can be effectively
      modified by the strain-induced phase transition. This evolution of
      antiferromagnetic-spin axes can be leveraged in exchange coupling between the
      antiferromagnetic Bi0.7La0.3FeO3 and a ferromagnetic Co0.9Fe0.1 layer to tune the
      ferromagnetic easy axis of the Co0.9Fe0.1. These results demonstrate that besides
      chemical alloying, epitaxial strain is an alternative and effective way to modify
      subtle phase relations and tune physical properties in rare earth-alloyed BiFeO3.
      Furthermore, the observation of antiferroelectric-antiferromagnetic properties in
      the Pbam Bi0.7La0.3FeO3 phase could be of significant scientific interest and
      great potential in magnetoelectric devices because of its dual antiferroic
      nature.

PMID- 29637779
TI  - Unique Color Converter Architecture Enabling Phosphor-in-Glass (PiG) Films
      Suitable for High-Power and High-Luminance Laser-Driven White Lighting.
AB  - As a next-generation high-power lighting technology, laser lighting has attracted
      great attention in high-luminance applications. However, thermally robust and
      highly efficient color converters suitable for high-quality laser lighting are
      scarce. Despite its versatility, the phosphor-in-glass (PiG) has been seldom
      applied in laser lighting because of its low thermal conductivity. In this work,
      we develop a unique architecture in which a phosphor-in-glass (PiG) film was
      directly sintered on a high thermally conductive sapphire substrate coated by one
      dimensional photonic crystals. The designed color converter with the composite
      architecture exhibits a high internal quantum efficiency close to that of the
      original phosphor powders and an excellent packaging efficiency up to 90%.
      Furthermore, the PiG film can even be survived under the 11.2 W mm-2 blue laser
      excitation. Combining blue laser diodes with the YAG-PiG-on-sapphire plate, a
      uniform white light with a high luminance of 845 Mcd m-2(luminous flux: 1839 lm),
      luminous efficacy of 210 lm W-1, and correlated color temperature of 6504 K was
      obtained. A high color rendering index of 74 was attained by adding a robust
      orange or red phosphor layer to the architecture. These outstanding properties
      meet the standards of vehicle regulations, enabling the PiG films with the
      composite architecture to be applied in automotive lighting or other high-power
      and high-luminance laser lighting.

PMID- 29637780
TI  - Analysis and Evaluation of the Inhibitory Mechanism of a Novel Angiotensin-I
      Converting Enzyme Inhibitory Peptide Derived from Casein Hydrolysate.
AB  - Casein hydrolysates exert various biological activities, and the responsible
      functional peptides are being identified from them continuously. In this study,
      the tryptic casein hydrolysate was fractionated by an ultrafiltration membrane (3
      kDa), and the peptides were identified by capillary electrophoresis-quadrupole
      time-of-flight-tandem mass spectrometry. Meanwhile, in silico methods were used
      to analyze the toxicity, solubility, stability, and affinity between the peptides
      and angiotensin-I-converting enzyme (ACE). Finally, a new angiotensin-I
      converting enzyme inhibitory (ACEI) peptide, EKVNELSK, derived from alphas1
      casein (fragment 35-42) was screened. The half maximal inhibitory concentration
      value of the peptide is 5.998 mM, which was determined by a high-performance
      liquid chromatography method. The Lineweaver-Burk plot indicated that this
      peptide is a mixed-type inhibitor against ACE. Moreover, Discovery Studio 2017 R2
      software was adopted to perform molecular docking to propose the potential
      mechanisms underlying the ACEI activity of the peptide. These results indicated
      that EKVNELSK is a new ACEI peptide identified from casein hydrolysate.

PMID- 29637781
TI  - Stereoselective Sequential [4+2]/[2+2] Cycloadditions Involving 2
      Alkenylindolenines: An Approach to Densely Functionalized Benzo[ b]indolizidines.
AB  - A stereoselective sequential [4+2]/[2+2] cycloaddition process involving 2
      alkenylindolenines has been developed. This unprecedented protocol allows a rapid
      access to densely functionalized benzo[ b]indolizidines containing a fully
      substituted piperidine ring with five contiguous stereogenic centers in good
      yields with excellent diastereoselectivities. This finding demonstrated the
      unique synthetic utility of the 2-alkenylindolenine species in the construction
      of complex polycyclic N-heterocycles.

PMID- 29637783
TI  - NIR-to-NIR Deep Penetrating Nanoplatforms Y2O3:Nd3+/Yb3+@SiO2@Cu2S toward Highly
      Efficient Photothermal Ablation.
AB  - A difunctional nano-photothermal therapy (PTT) platform with near-infrared
      excitation to near-infrared emission (NIR-to-NIR) was constructed through core
      shell structures Y2O3:Nd3+/Yb3+@SiO2@Cu2S (YRSC), in which the core
      Y2O3:Nd3+/Yb3+ and shell Cu2S play the role of bioimaging and photothermal
      conversion function, respectively. The structure and composition of the present
      PTT agents (PTAs) were characterized by powder X-ray diffraction, field emission
      scanning electron microscopy, transmission electron microscopy, and X-ray
      photoelectron spectra. The NIR emissions of samples in the biological window area
      were measured by photoluminescence spectra under the excitation of 808 nm laser;
      further, the penetration depth of NIR emission at different wavelengths in
      biological tissue was also demonstrated by comparing with visible (vis) emission
      from Y2O3:Yb3+/Er3+@SiO2@Cu2S and NIR emission from YRSC through different
      injection depths in pork muscle tissues. The photo-thermal conversion effects
      were achieved through the outer ultrasmall Cu2S nanoparticles simultaneously
      absorb NIR light emission from the core Y2O3:Nd3+/Yb3+ and the 808 nm excitation
      source to generate heat. Further, the heating effect of YRSC nanoparticles was
      confirmed by thermal imaging and ablation of YRSC to Escherichia coli and human
      hepatoma (HepG-2) cells. Results indicate that the YRSC has potential
      applications in PTT and NIR imaging in biological tissue.

PMID- 29637784
TI  - Correction to "Synthesis of (+)-Disparlure via Enantioselective
      Iodolactonization".

PMID- 29637782
TI  - Conformational Dynamics in the Binding-Protein-Independent Mutant of the
      Escherichia coli Maltose Transporter, MalG511, and Its Interaction with Maltose
      Binding Protein.
AB  - MalG511 is a genetically selected binding-protein-independent mutant of the
      Escherichia coli maltose transporter MalFGK2, which retains specificity for
      maltose and shows a high basal ATPase activity in the absence of maltose binding
      protein (MBP). It shows an intriguing biphasic behavior in maltose transport
      assays in the presence of MBP, with low levels of MBP stimulating the activity
      and higher levels (>50 MUM) inhibiting the transport activity. Remarkably, the
      rescuing effect of the MBP suppressor mutant, MBPG13D, turns it into an
      attractive model for studying regulatory mechanisms in the ABC transporter
      superfamily. It is hypothesized that the special characteristics of MalG511
      result from mutations that shift its equilibrium toward the transition state of
      MalFGK2. We tested this hypothesis by using site-directed spin labeling in
      combination with electron paramagnetic resonance spectroscopy, which showed
      conformational changes in MalG511 and its interaction with MBP and MBPG13D during
      its catalytic cycle. We found that MalG511 utilizes the same alternate access
      mechanism as MalFGK2, including all three open, semi-open, and closed states of
      the MalK dimer, to transport maltose across the membrane. However, the
      equilibrium of this mutant is shifted toward the semi-open state in its resting
      state and interacts with MBP with high affinity, providing an explanation for the
      inhibition of MalG511 by MBP at higher concentrations. In contrast, the mutant
      binding protein, MBPG13D, interacts with lower affinity and could restore MalG511
      to a normal catalytic cycle.

PMID- 29637785
TI  - Direct Evidence of Exciton-Exciton Annihilation in Single-Crystalline Organic
      Metal Halide Nanotube Assemblies.
AB  - Excitons in low-dimensional organic-inorganic metal halide hybrid structures are
      commonly thought to undergo rapid self-trapping following creation due to strong
      quantum confinement and exciton-phonon interaction. Here we report an
      experimental study probing the dynamics of these self-trapped excitons in the
      single-crystalline bulk assemblies of 1D organic metal halide nanotubes,
      (C6H13N4)3Pb2Br7. Through time-resolved photoluminescence (PL) measurements at
      different excitation intensities, we observed a marked variation in the PL decay
      behavior that is manifested by an accelerated decay rate with increasing
      excitation fluence. Our results offer direct evidence of the occurrence of an
      exciton-exciton annihilation process, a nonlinear relaxation phenomenon that
      takes place only when some of the self-trapped excitons become mobile and can
      approach either each other or those trapped excitons. We further identify a fast
      and dominant PL decay component with a lifetime of ~2 ns with a nearly invariant
      relative area for all acquired PL kinetics, suggesting that this rapid relaxation
      process is intrinsic.

PMID- 29637786
TI  - Corrigendum.

PMID- 29637787
TI  - Prevalence of metabolic syndrome among middle-aged and elderly adults in China:
      current status and temporal trends.
AB  - BACKGROUND: Metabolic syndrome (MetS) is a cluster of major risk factors for
      cardiovascular diseases. We aimed to estimate prevalence and distribution of MetS
      among middle-aged and elderly adults in China. METHODS: The present analysis used
      data from a national study in 2014-2015. We defined MetS by different
      definitions, and compared results of the present study and previous nationally
      representative studies to illustrate possible temporal changes in MetS
      prevalence. RESULTS: The estimated prevalence of MetS was 18.4% by the ATP III
      criteria, 34.0% by the revised ATP III criteria, and 26.9% by IDF criteria. The
      prevalence was higher in women, older adults, those with lower education level,
      and in economically developed regions. Contrasting with previous national
      studies, adults in urban areas had a lower rate of MetS than those in rural areas
      (odds ratio 0.94; 95% CI 0.92-0.97). Rural adults had worse deterioration or less
      improvement in abdominal obesity, overweight, hypertension, and high fasting
      plasma glucose, than urban adults, which was particularly striking for women.
      CONCLUSION: While measures to prevent and control cardiovascular diseases need to
      be strengthened in China, rapid increasing risk factors among rural residents and
      women should be prioritized in making public health policy decisions. KEY
      MESSAGES Our study assessed prevalence and temporal changes of MetS among Chinese
      population with the most recently completed and the largest sample size. The
      current prevalence of MetS was higher in women, older adults, those with lower
      education level, and in economically developed regions and the CVD risk factors
      among rural residents and women should be prioritised in making public health
      policy decisions. A comparison of results of the present study and previous
      national studies showed that rural adults had worse deterioration or less
      improvement in abdominal obesity, overweight, hypertension, and high fasting
      plasma glucose, than urban adults, which was particularly striking for women.

PMID- 29637788
TI  - Thyroid-stimulating hormone and adverse left ventricular remodeling following ST
      segment elevation myocardial infarction.
AB  - BACKGROUND: Adverse left ventricular remodeling is one of the major determinants
      of heart failure and mortality in patients surviving ST-segment elevation
      myocardial infarction (STEMI). The hypothalamic-pituitary-thyroid axis is a key
      cardiovascular regulator; however, the relationship between hypothalamic
      pituitary-thyroid status and post-STEMI left ventricular remodeling is unclear.
      We aimed to investigate the association between thyroid-stimulating hormone
      concentrations and the development of left ventricular remodeling following
      reperfused STEMI. METHODS: In this prospective observational study of 102
      consecutive STEMI patients, thyroid-stimulating hormone levels were measured at
      the first day after infarction and 4 months thereafter. Cardiac magnetic
      resonance scans were performed within the first week as well as at 4 months
      follow-up to determine infarct characteristics, myocardial function and as
      primary endpoint left ventricular remodeling, defined as a 20% or greater
      increase in left ventricular end-diastolic volume. RESULTS: Patients with left
      ventricular remodeling ( n=15, 15%) showed significantly lower concentrations of
      baseline (1.20 [0.92-1.91] vs. 1.73 [1.30-2.60] mU/l; P=0.02) and follow-up (1.11
      [0.86-1.28] vs. 1.51 [1.15-2.02] mU/l; P=0.002) thyroid-stimulating hormone. The
      association between baseline thyroid-stimulating hormone and left ventricular
      remodeling remained significant after adjustment for major clinical (peak high
      sensitivity cardiac troponin T and C-reactive protein, heart rate; odds ratio
      (OR) 5.33, 95% confidence interval (CI) 1.52-18.63; P=0.01) and cardiac magnetic
      resonance predictors of left ventricular remodeling (infarct size, microvascular
      obstruction, ejection fraction; OR 4.59, 95% CI 1.36-15.55; P=0.01). Furthermore,
      chronic thyroid-stimulating hormone was related to left ventricular remodeling
      independently of chronic left ventricular remodeling correlates (infarct size,
      ejection fraction, left ventricular end-diastolic volume, left ventricular end
      systolic volume; OR 9.22, 95% CI 1.69-50.22; P=0.01). CONCLUSIONS: Baseline and
      chronic thyroid-stimulating hormone concentrations following STEMI were
      independently associated with left ventricular remodeling, proposing a novel
      pathophysiological axis in the development of post-STEMI left ventricular
      remodeling.

PMID- 29637789
TI  - Do preclinical studies suggest that CD99 is a potential therapeutic target in
      acute myeloid leukemia and the myelodysplastic syndromes?
AB  - INTRODUCTION: Acute myeloid leukemia (AML) and the myelodysplastic syndromes
      (MDS) are clonal hematopoietic neoplasms that arise from leukemia stem cells
      (LSCs) and hematopoietic stem cells (HSCs), respectively. Standard chemotherapy
      can efficiently eliminate the bulk of neoplastic cells, however, LSCs and MDS
      HSCs are relatively resistant to these therapies and can reinitiate and maintain
      disease. CD99 is a 32-kDa transmembrane polypeptide that is highly expressed on
      disease stem cells in the vast majority of AML and MDS. Areas covered: In this
      editorial, we focus on the current literature surrounding the identification of
      CD99 as a marker of MDS and AML stem cells and preclinical studies revealing the
      therapeutic efficacy of targeting CD99 in these diseases. Expert
      opinion/commentary: Cytotoxic CD99 monoclonal antibodies represent promising stem
      cell-directed therapies that have the potential to markedly improve clinical
      outcomes for these difficult-to-treat hematologic malignancies.

PMID- 29637790
TI  - Interobserver reliability of the ankle-brachial index, toe-brachial index and
      distal pulse palpation in patients with diabetes.
AB  - OBJECTIVE: We conducted a prospective pilot study in patients with diabetes to
      analyse the interobserver reliability of the ankle-brachial index, toe-brachial
      index and distal pulse palpation depending on the training of the professional
      involved. MATERIALS AND METHODS: The ankle-brachial index, toe-brachial index and
      distal pulses were assessed by three clinicians with different levels of
      experience on the same day. Measurements were supervised and recorded by a fourth
      clinician. RESULTS: Twenty-one patients (42 ft) were included in this study. We
      observed moderate agreement between clinicians in the palpation of posterior
      tibial arteries (K = 0.45, p < 0.001) and low agreement in dorsalis pedis
      arteries (K = 0.33, p < 0.001). The measurement of ankle-brachial index had
      moderate agreement between clinicians in patients with medial arterial
      calcification (K = 0.43, p < 0.001) and low agreement in patients with normal
      ankle-brachial index (K = 0.4, p < 0.001). The measurement of toe-brachial index
      had moderate agreement between clinicians in patients with a normal toe-brachial
      index (K = 0.4, p < 0.001) and in patients with medial arterial calcification (K
      = 0.60, p < 0.001). CONCLUSION: Palpation of distal pulses, ankle-brachial index
      and toe-brachial index determination in patients with diabetes are not highly
      reproducible and reliable between clinicians with different levels of experience
      under routine conditions.

PMID- 29637791
TI  - Measuring Value in Internal Medicine Residency Training Hospitals Using Publicly
      Reported Measures.
AB  - Graduate medical education (GME) lacks measures of resident preparation for high
      quality, cost-conscious practice. The authors used publicly reported teaching
      hospital value measures to compare internal medicine residency programs on high
      value care training and to validate these measures against program director
      perceptions of value. Program-level value training scores were constructed using
      Centers for Medicare & Medicaid Services Value-Based Purchasing (VBP) Program
      hospital quality and cost-efficiency data. Correlations with Association of
      Program Directors in Internal Medicine Annual Survey high-value care training
      measures were examined using logistic regression. For every point increase in
      program-level VBP score, residency directors were more likely to agree that GME
      programs have a responsibility to contain health care costs (adjusted odds ratio
      [aOR] 1.18, P = .04), their faculty model high-value care (aOR 1.07, P = .03),
      and residents are prepared to make high-value medical decisions (aOR 1.07, P =
      .09). Publicly reported clinical data offer valid measures of GME value training.

PMID- 29637792
TI  - Osteopathic Manipulative Treatment in Surgical Care: Short Review of Research
      Publications in Osteopathic Journals During the Period 1990 to 2017.
AB  - BACKGROUND: A growing trend in surgical care is the investigation and
      incorporation of multimodal interventions into standardized programs.
      Additionally, manual therapies such as osteopathic manipulative treatment (OMT)
      are being used with patients in surgical care. Yet the scientific dialogue and
      the use of OMT in surgical care are currently insubstantial. OBJECTIVE: The aim
      of this study was to present an overview of published research articles within
      the subject field of OMT in surgical care. METHOD: Summative review of peer
      reviewed research articles published in osteopathic journals during the period
      1990 to 2017. In total, 10 articles were identified. RESULT: Previous research
      has been conducted within the areas of abdominal, thoracic, gynecological, and/or
      orthopedic surgery with measured outcomes such as pain, analgesia consumption,
      length of hospital stay, and range of motion. Heterogeneity was identified in
      usage of osteopathic techniques, treatment duration, and occurrence, as well as
      in the treating osteopath's experience. CONCLUSION: Despite the small number of
      research articles within this field, both positive measured effects as well as
      the absence of such effects were identified. Overall, there was a heterogeneity
      concerning surgical contexts, diagnoses, signs and symptoms, as well as surgical
      phases in current interprofessional osteopathic publications. In this era of
      multimodal surgical care, we argue that there is an urgent need to evaluate OMT
      in this context of care and with a proper research approach.

PMID- 29637794
TI  - Population impact of the 2017 ACC/AHA guidelines compared with the 2013 ESH/ESC
      guidelines for hypertension management.
AB  - Background The 2017 ACC/AHA guidelines on hypertension management recommend the
      introduction of antihypertensive treatment for patients with new stage 1
      hypertension thresholds (130-139/80-89 mm Hg) and with a cardiovascular disease
      or related condition. We compared the Swiss population and economic impact of
      antihypertensive treatment of the 2017 ACC/AHA guidelines with the 2013 European
      guidelines. Methods Analyses were based on 4438 participants (aged 45-85 years;
      2448 women) of the CoLaus|PsyCoLaus study recruited between 2014-2017.
      Participants eligible for antihypertensive treatment according to the 2017
      ACC/AHA and 2013 European guidelines were sex and age standardised using the
      Swiss population for 2016. In addition, we estimated the population-wide annual
      costs of antihypertensive treatment. Results Individuals eligible for
      antihypertensive treatment were 40.3% (95% confidence interval 38.5-42.1) and
      31.3% (29.7-32.9) according to the 2017 ACC/AHA and 2013 European guidelines,
      respectively. That difference would translate into approximately 250,000
      additional individuals eligible for antihypertensive treatment, corresponding to
      an additional annual cost of 72.5 million CHF (63.0 million EUR). Conclusion The
      2017 ACC/AHA guidelines on the management of hypertension substantially increase
      the number of individuals eligible for antihypertensive treatment compared to the
      2013 European guidelines. While implementation of the 2017 ACC/AHA guidelines is
      expected to lead to cost reduction by preventing cardiovascular diseases, that
      reduction might be mitigated by the costs incurred by antihypertensive treatments
      in a larger proportion of the population.

PMID- 29637795
TI  - Environmental post-processing increases the adhesion strength of mussel byssus
      adhesive.
AB  - Marine mussels (Mytilus trossulus) attach to a wide variety of surfaces
      underwater using a protein adhesive that is cured by the surrounding seawater
      environment. In this study, the influence of environmental post-processing on
      adhesion strength was investigated by aging adhesive plaques in a range of
      seawater pH conditions. Plaques took 8-12 days to achieve full strength at pH 8,
      nearly doubling in adhesion strength (+94%) and increasing the work required to
      dislodge (+59%). Holding plaques in low pH conditions prevented strengthening,
      causing the material to tear more frequently under tension. The timescale of
      strengthening is consistent with the conversion of DOPA to DOPA-quinone, a pH
      dependent process that promotes cross-linking between adhesive proteins. The
      precise arrangement of DOPA containing proteins away from the adhesive-substratum
      interface emphasizes the role that structural organization can have on function,
      an insight that could lead to the design of better synthetic adhesives and metal
      coordinating hydrogels.

PMID- 29637796
TI  - How researchers perceive research misconduct in biomedicine and how they would
      prevent it: A qualitative study in a small scientific community.
AB  - The aim of our study has been to use a qualitative approach to explore the
      potential motivations and drivers for unethical behaviors in biomedicine and
      determine the role of institutions regarding those issues in a small scientific
      community setting. Three focus groups were held---two with doctoral students and
      one with active senior researchers. Purposive sampling was used to reach
      participants at different stages of their scientific careers. Participants in all
      three focus groups were asked the same questions regarding the characteristics
      and behaviors of ethical/unethical scientists, ethical climate, role, and
      responsibility of institutions; they were also asked to suggest ways to improve
      research integrity. The data analysis included coding of the transcripts,
      categorization of the initial codes, and identification of themes and patterns.
      Three main topics were derived from the focus groups discussions. The first
      included different forms of unethical behaviors including increasing research
      "waste," non-publication of negative results, authorship manipulation, data
      manipulation, and repression of collaborators. The second addressed the factors
      influencing unethical behavior, both external and internal, to the researchers.
      Two different definitions of ethics in science emerged; one from the categorical
      perspective and the other from the dimensional perspective. The third topic
      involved possible routes for improvement, one from within the institution through
      the research integrity education, research integrity bodies, and quality control,
      and the other from outside the institution through external supervision of
      institutions. Based on the results of our study, research misconduct in a small
      scientific community is perceived to be the consequence of the interaction of
      several social and psychological factors, both general and specific, for small
      research communities. Possible improvements should be systematic, aiming both for
      improvements in work environment and personal awareness in research ethics, and
      the implementation of those changes should be institutional responsibility.

PMID- 29637797
TI  - Ultrasound-guided percutaneous microwave ablation versus surgery for papillary
      thyroid microcarcinoma.
AB  - BACKGROUND: Papillary thyroid microcarcinoma (PTMC) has high incidence and low
      disease-specific mortality. However, active surveillance is not accepted by most
      patients owing to high physical or psychological pressures. The emergence of
      ablation technologies is supplanting traditional surgery. Our goal was to compare
      the clinical outcomes of microwave ablation (MWA) and surgery for T1aN0M0 PTMC.
      METHODS: A total of 92 consecutive patients with T1aN0M0 PTMC were studied
      retrospectively. Forty-six patients had been treated with MWA, and the other 46
      had undergone surgery. MWA was performed using extensive ablation extending from
      the nodule's lower pole to the upper pole. Surgery was performed by total
      thyroidectomy or thyroid lobectomy. We compared the two groups in terms of mean
      length of stay, cost, mean blood loss, surgical incision, operating room (OR)
      time, quality of life (QOL) assessment, complications, and therapeutic efficacy
      over a follow-up period of 42 months. RESULTS: The mean length of stay, cost,
      mean blood loss, surgical incisions, OR time, and complications in the MWA group
      were significantly lower than those of the surgery group. The QOL after MWA was
      higher than it was after surgery. The nodule volume decreased significantly from
      53.61 +/- 48.43 mm3 to 4.84 +/- 6.55 mm3 (p < .001) at the 42-month follow-up,
      exhibiting a percentage volume reduction of 81.33 +/- 36.87%. No recurrence or
      metastasis occurred in either group during the follow-up period. CONCLUSIONS: MWA
      may be considered a minimally invasive alternative to surgery for solitary
      T1aN0M0 PTMC with low incidence of complications and good therapeutic effect.

PMID- 29637793
TI  - Functions of the sirtuin deacylase SIRT5 in normal physiology and pathobiology.
AB  - Sirtuins are NAD+-dependent protein deacylases/ADP-ribosyltransferases that have
      emerged as candidate targets for new therapeutics to treat metabolic disorders
      and other diseases, including cancer. The sirtuin SIRT5 resides primarily in the
      mitochondrial matrix and catalyzes the removal of negatively charged lysine acyl
      modifications; succinyl, malonyl, and glutaryl groups. Evidence has now
      accumulated to document the roles of SIRT5 as a significant regulator of cellular
      homeostasis, in a context- and cell-type specific manner, as has been observed
      previously for other sirtuin family members. SIRT5 regulates protein substrates
      involved in glycolysis, the TCA cycle, fatty acid oxidation, electron transport
      chain, ketone body formation, nitrogenous waste management, and ROS
      detoxification, among other processes. SIRT5 plays pivotal roles in cardiac
      physiology and stress responses and is involved in the regulation of numerous
      aspects of myocardial energy metabolism. SIRT5 is implicated in neoplasia, as
      both a tumor promoter and suppressor in a context-specific manner, and may serve
      a protective function in the setting of neurodegenerative disorders. Here, we
      review the current understanding of functional impacts of SIRT5 on its metabolic
      targets, and its molecular functions in both normal and pathological conditions.
      Finally, we will discuss the potential utility of SIRT5 as a drug target and also
      summarize the current status, progress, and challenges in developing small
      molecule compounds to modulate SIRT5 activity with high potency and specificity.

PMID- 29637798
TI  - Levonorgestrel-releasing intra-uterine systems as female contraceptives.
AB  - INTRODUCTION: The availability and use of long-acting reversible contraceptives
      (LARCs), such as levonorgestrel intrauterine systems (LNG-IUSs), have increased
      in recent times. Areas covered: The authors provide a narrative review of the LNG
      IUSs currently available worldwide as female contraceptives (LNG-IUS 13.5, 19.5
      and 52 mg). Specific features of the devices and their parameters of efficacy and
      tolerability were considered as outcomes. Expert opinion: The one-handed 3.8-mm
      diameter inserter of LNG-IUS 13.5 mg and 19.5 mg may be particularly suitable in
      nulliparous women. While LNG-IUSs 13.5, 19.5 mg and LNG 52 mg should be used by
      women simply looking for an effective contraceptive method for up to 3, 4 or 5
      years, LNG-IUS 52 mg has also been approved for the treatment of heavy menstrual
      bleeding and endometrial protection during hormone replacement therapy. LNG-IUS
      52 mg is ideal for women who are experiencing a certain hyperestrogenic hormonal
      environment, with heavy menstrual bleeding due to hormonal imbalances,
      adenomyosis or fibroids, in the case of symptomatic endometriosis or for
      endometrial protection during hormone estrogenic replacement therapy in non
      hysterectomized women.

PMID- 29637799
TI  - Immunogenicity testing of therapeutic antibodies in ocular fluids after
      intravitreal injection.
AB  - AIM: High drug concentrations in ocular fluids after intravitreal administration
      preclude the use of drug-sensitive immunoassays. A drug-tolerant immunoassay is
      therefore desirable for immunogenicity testing in ophthalmology. EXPERIMENTAL:
      Immune complex (IC) antidrug antibody (ADA) assays were established for two
      species. The assays were compared with the bridging assay in ocular and plasma
      samples from two preclinical studies. RESULTS: The IC assays showed high drug
      tolerance, which enabled a reliable ADA detection in ocular fluids after
      intravitreal administration. The IC assays were superior to the bridging assay in
      the analysis of ocular fluids with high drug concentrations. CONCLUSION: The IC
      assay allows a reliable ADA detection in matrices with high drug concentrations,
      such as ocular fluids.

PMID- 29637800
TI  - Exploratory and confirmatory factor analyses and invariance assessment of the
      perceived powerlessness scale among youth in Baltimore.
AB  - Generalized perceived powerlessness is an important psychosocial construct that
      determines a wide range of health behaviors and outcomes. This study has two
      aims: (1) examine the structure of the newly developed perceived powerlessness
      scale using exploratory and confirmatory factor analyses and (2) assess the
      scale's invariance across key demographic variables using multi-group
      confirmatory factor analysis among a random household sample of African American
      and White youth (aged 15-24 years) residing in Baltimore, MD. Our study results
      demonstrated that the powerlessness scale is valid among a demographically
      diverse sample of urban youth, showing promise for use in future health behavior
      and outcome studies.

PMID- 29637802
TI  - Corrigendum.

PMID- 29637801
TI  - Increased risk of polycystic ovary syndrome (PCOS) associated with CC genotype of
      miR-146a gene variation.
AB  - Polycystic ovary syndrome (PCOS) is an endocrinopathy in reproductive-age women
      believed to be affected by several genetics and environmental factors or both.
      Different miRNAs are one of such genetic factors that their associations with
      PCOS have been implicated. For instance, miR-146a that is well known for strongly
      regulating the immune response and inflammation was upregulated in serum plasma,
      follicular fluid and granulosa cells of PCOS patients. Different studies have
      shown that genetic changes in pre-miRNA can cause change in the expression or
      biological function of mature miRNA. Therefore, the main aim of this study was to
      investigate the association of miR-146a gene variation (rs2910164) with the
      susceptibility to PCOS. This study consists of 180 patients with PCOS and 192
      healthy women matched by age and geographical region. Genotyping were determined
      by using PCR-RFLP in all subjects. The genotype frequency and allele
      distributions of all subjects were evaluated using Fisher's exact test directed
      by SPSS v.20. The genotype and allele frequencies of the miR-146a polymorphism
      (rs2910164) significantly differ between PCOS and healthy controls. The
      frequencies of CC genotype (p = .054) and 'C' allele (p = .0001) of the miR-146a
      variant indicated a significant incidence in cases compared to controls. Such
      association was obtained in co-dominant (OR = 3.16) and dominant (OR = 2.29)
      models. Result of this study can be proposed that women with miR-146a variation
      are at a higher risk for developing PCOS, which can be due to up-regulation of
      miR-146a.

PMID- 29637803
TI  - Musculoskeletal multibody dynamics simulation of the contact mechanics and
      kinematics of a natural knee joint during a walking cycle.
AB  - Detailed knowledge of the in vivo loading and kinematics in the knee joint is
      essential to understand its normal functions and the aetiology of osteoarthritis.
      Computer models provide a viable non-invasive solution for estimating joint
      loading and kinematics during different physiological activities. However, the
      joint loading and kinematics of the tibiofemoral and patellofemoral joints during
      a gait cycle were not typically investigated concurrently in previous
      computational simulations. In this study, a natural knee architecture was
      incorporated into a lower extremity musculoskeletal multibody dynamics model
      based on a force-dependent kinematics approach to investigate the contact
      mechanics and kinematics of a natural knee joint during a walking cycle.
      Specifically, the contact forces between the femoral/tibial articular cartilages
      and menisci and between the femoral and tibial/patellar articular cartilages were
      quantified. The contact forces and kinematics of the tibiofemoral and
      patellofemoral joints and the muscle activations and ligament forces were
      predicted simultaneously with a reasonable level of accuracy. The developed
      musculoskeletal multibody dynamics model with a natural knee architecture can
      serve as a potential platform for assisting clinical decision-making and
      postoperative rehabilitation planning.

PMID- 29637804
TI  - Terror in time: extending culturomics to address basic terror management
      mechanisms.
AB  - Building on Google's efforts to scan millions of books, this article introduces
      methodology using a database of annual word frequencies of the 40,000 most
      frequently occurring words in the American literature between 1800 and 2009. The
      current paper uses this methodology to replicate and identify terror management
      processes in historical context. Variation in frequencies of word usage of
      constructs relevant to terror management theory (e.g. death, worldview, self
      esteem, relationships) are investigated over a time period of 209 years. Study 1
      corroborated previous TMT findings and demonstrated that word use of constructs
      related to death and of constructs related to patriotism and romantic
      relationships significantly co-vary over time. Study 2 showed that the use of the
      word "death" most strongly co-varies over time with the use of medical
      constructs, but also co-varies with the use of constructs related to violence,
      relationships, religion, positive sentiment, and negative sentiment. Study 3
      found that a change in the use of death related words is associated with an
      increase in the use of fear related words, but not in anxiety related words.
      Results indicate that the described methodology generates valuable insights
      regarding terror management theory and provide new perspectives for theoretical
      advances.

PMID- 29637805
TI  - Noncoding RNAs and Stroke.
AB  - Over many years, extensive efforts have focused on the development and
      improvement of diagnostic and therapeutic strategies to reduce stroke-associated
      neurovascular damage, such as blood-brain barrier dysfunction, brain edema,
      parenchymal inflammation, and neural cell death. However, the only clinically
      applied pharmacological therapy to date for the treatment of acute ischemic
      stroke is thrombolysis. Because of the short therapeutic window of current
      thrombolytic therapy and the activation of various pathophysiological signaling
      cascades triggered after ischemic stroke, the development of new therapies is
      urgently required. Noncoding RNAs (ncRNAs) are defined as untranslated regulatory
      RNA molecules. Although ncRNAs with biological roles have been known for almost
      60 years, they have within the past decade emerged as key mediators of
      posttranscriptional gene expression/function in pathological aspects of ischemic
      stroke. With properties of relative stability, specificity, and reproducibility,
      ncRNAs are considered to be promising as biomarkers and better candidates than
      proteins and genes for early recognition of the onset of disease. In this update,
      we summarized the current knowledge for three groups of ncRNAs in stroke,
      focusing on the role of long noncoding RNAs and circular RNAs as biomarkers for
      stroke and as targets for regulating large sets of genes in related pathways
      after ischemic stroke.

PMID- 29637806
TI  - Cognitive reappraisal attenuates the association between depressive symptoms and
      emotional response to stress during adolescence.
AB  - Depression is associated with increased emotional response to stress. This is
      especially the case during the developmental period of adolescence. Cognitive
      reappraisal is an effective emotion regulation strategy that has been shown to
      reduce the impact of emotional response on psychopathology. However, less is
      known about whether cognitive reappraisal impacts the relationship between
      depressive symptoms and emotional responses, and whether its effects are specific
      to emotional reactivity or emotional recovery. The current study examined whether
      cognitive reappraisal moderated the relationship between depressive symptoms and
      trait or state measures of emotional reactivity and recovery. A community sample
      of 127 adolescents (M-age = 15.28; 49% female, 47% Caucasian), at an age of risk
      for depression, completed self-report measures of trait emotional responding and
      depressive symptoms. In addition, they completed an in vivo social stress task
      and were assessed on state emotional reactivity and recovery from the stressor.
      Findings suggested that cognitive reappraisal was associated with an attenuated
      impact of depressive symptoms on trait and state emotional recovery. These
      results provide evidence that cognitive reappraisal may be an effective strategy
      for improving some aspects of emotional responding in relation to depressive
      symptoms among adolescents.

PMID- 29637808
TI  - Retail Deli Slicer Inspection Practices: An EHS-Net Study.
AB  - The Centers for Disease Control and Prevention (CDC) estimates that 3,000 people
      die in the United States each year from foodborne illness, and Listeria
      monocytogenes causes the third highest number of deaths. Risk assessment data
      indicate that L. monocytogenes contamination of particularly delicatessen meats
      sliced at retail is a significant contributor to human listeriosis. Mechanical
      deli slicers are a major source of L. monocytogenes cross-contamination and
      growth. In an attempt to prevent pathogen cross-contamination and growth, the
      U.S. Food and Drug Administration (FDA) created guidance to promote good slicer
      cleaning and inspection practices. The CDC's Environmental Health Specialists
      Network conducted a study to learn more about retail deli practices concerning
      these prevention strategies. The present article includes data from this study on
      the frequency with which retail delis met the FDA recommendation that slicers
      should be inspected each time they are properly cleaned (defined as
      disassembling, cleaning, and sanitizing the slicer every 4 h). Data from food
      worker interviews in 197 randomly selected delis indicate that only 26.9% of
      workers ( n = 53) cleaned and inspected their slicers at this frequency. Chain
      delis and delis that serve more than 300 customers on their busiest day were more
      likely to have properly cleaned and inspected slicers. Data also were collected
      on the frequency with which delis met the FDA Food Code provision that slicers
      should be undamaged. Data from observations of 685 slicers in 298 delis indicate
      that only 37.9% of delis ( n = 113) had slicers that were undamaged. Chain delis
      and delis that provide worker training were more likely to have slicers with no
      damage. To improve slicer practices, food safety programs and the retail food
      industry may wish to focus on worker training and to focus interventions on
      independent and smaller delis, given that these delis were less likely to
      properly inspect their slicers and to have undamaged slicers.

PMID- 29637809
TI  - Heavy Metals in Selected Vegetables from Markets of Faisalabad, Pakistan.
AB  - Two hundred ten samples of selected vegetables (okra, pumpkin, tomato, potato,
      eggplant, spinach, and cabbage) from Faisalabad, Pakistan, were analyzed for the
      analysis of heavy metals: cadmium (Cd), lead (Pb), arsenic (As), and mercury
      (Hg). Inductively coupled plasma optical emission spectrometry was used for the
      analysis of heavy metals. The mean levels of Cd, Pb, As, and Hg were 0.24, 2.23,
      0.58, and 7.98 mg/kg, respectively. The samples with Cd (27%), Pb (50%), and Hg
      (63%) exceeded the maximum residual levels set by the European Commission. The
      mean levels of heavy metals found in the current study are high and may pose
      significant health concerns for consumers. Furthermore, considerable attention
      should be paid to implement comprehensive monitoring and regulations.

PMID- 29637807
TI  - The potential mechanism of mitochondrial dysfunction in septic cardiomyopathy.
AB  - Septic cardiomyopathy is one of the most serious complications of sepsis or
      septic shock. Basic and clinical research has studied the mechanism of cardiac
      dysfunction for more than five decades. It has become clear that myocardial
      depression is not related to hypoperfusion. As the heart is highly dependent on
      abundant adenosine triphosphate (ATP) levels to maintain its contraction and
      diastolic function, impaired mitochondrial function is lethally detrimental to
      the heart. Research has shown that mitochondria play an important role in organ
      damage during sepsis. The mitochondria-related mechanisms in septic
      cardiomyopathy have been discussed in terms of restoring mitochondrial function.
      Mitochondrial uncoupling proteins located in the mitochondrial inner membrane can
      promote proton leakage across the mitochondrial inner membrane. Recent studies
      have demonstrated that proton leakage is the essential regulator of mitochondrial
      membrane potential and the generation of reactive oxygen species (ROS) and ATP.
      Other mechanisms involved in septic cardiomyopathy include mitochondrial ROS
      production and oxidative stress, mitochondria Ca2+ handling, mitochondrial DNA in
      sepsis, mitochondrial fission and fusion, mitochondrial biogenesis, mitochondrial
      gene regulation and mitochondria autophagy. This review will provide an overview
      of recent insights into the factors contributing to septic cardiomyopathy.

PMID- 29637810
TI  - Detection and Quantitation of Lomefloxacin and Pefloxacin Residues in the Organ
      Tissues and Eggs of Laying Hens.
AB  - Lomefloxacin (LOM) and pefloxacin (PEF) are synthetic antibiotics that have been
      used in the treatment of infectious diseases in both human and animals. In the
      People's Republic of China, the use of LOM and PEF in livestock has been
      prohibited because of the concern that the residues of these drugs may pose a
      risk to public health. Despite this prohibition, these drugs are still being used
      in the poultry industry illegally, and so far there has been no systematic study
      of the persistence of LOM and PEF residues in chickens. In this study, laying
      hens were treated with a daily dose (10 mg/kg of body weight) of LOM or PEF for
      five consecutive days, and the drug residues in various tissues and eggs were
      determined over a 15-day period after the last drug administration. The highest
      LOM and PEF residual concentrations were found in the tissues 4 h after the last
      drug administration, and concentrations gradually decreased over time. Plasma had
      the lowest and liver had the highest residual concentrations throughout the 15
      day study period. At the end of the 15 days, 3.64 +/- 0.74 MUg/kg LOM and 1.78 +/
      0.28 MUg/kg PEF were detected in the liver, with slightly lower residual
      concentrations in the kidney. No LOM or PEF residue was detected in the ovarian
      follicle, plasma, and muscle at the end of the 15 days. In eggs, the depletion
      rate of LOM was slower than that of PEF. LOM and PEF residues were detected in
      whole eggs for up to 10 and 8 days, respectively, after drug administration
      ceased. These findings suggest that the liver and, to a lesser extent, the kidney
      may be the sites where LOM or PEF residues would persist. This information can be
      a reliable reference for governmental agencies with respect to the screening of
      LOM and PEF residues in food products derived from laying hens.

PMID- 29637812
TI  - Preserving Basement Membranes during Detachment of Cultivated Oral Mucosal
      Epithelial Cell Sheets for the Treatment of Total Bilateral Limbal Stem Cell
      Deficiency.
AB  - Total bilateral limbal stem cell deficiency leading to loss of corneal clarity,
      potential vision loss, pain, photophobia, and keratoplasty failure cannot be
      treated by autologous limbal transplantation, and allogeneic limbal
      transplantation requires subsequent immunosuppressive treatment. Cultured
      autologous oral mucosal epithelial cells have been shown to be safe and effective
      alternatives. These cells can be transplanted on supports or without support
      after detachment from the culture dishes. Dispase, known for epidermal sheet
      detachment, is reported as not usable for oral mucosa. The objective was to find
      an optimized detachment method providing a sufficiently resistant and adhesive
      cultured oral mucosal epithelium (COME), which can be grafted without sutures.
      Enzymatic treatments (dispase or collagenase at different concentrations) were
      compared to enzyme-free mechanical detachment. Histological immunofluorescence
      (IF) and Western blotting (WB) were used to examine the impact on adhesion
      markers (laminin-332, beta1-integrin, and type VII collagen) and junctional
      markers (E-cadherin, P-cadherin). Finally, the COME ability to adhere to the
      cornea and produce a differentiated epithelium 15 d after grafting onto an ex
      vivo porcine stroma model were investigated by histology, IF, and transmission
      electron microscopy. Collagenase at 0.5 mg/mL and dispase at 5 mg/mL were
      selected for comparative study on adhesive expression marker by IF and WB showed
      that levels of basement membrane proteins and cell-cell and cell-matrix junction
      proteins were not significantly different between the 3 detachment methods.
      Collagenase 0.5 mg/mL was selected for the next step validation because of the
      better reproducibility, 100% success (vs. 33% with dispase 5 mg/mL). Grafted onto
      porcine de-epithelialized corneal stroma, collagenase 0.5 mg/mL detached COME
      were found to adhere, stratify, and continue to ensure renewal of the epithelium.
      For COME, collagenase 0.5 mg/mL enzymatic detachment was selected and validated
      on its resistance and adhesive marker expression as well as their anchorage onto
      our new ex vivo de-epithelialized stroma model.

PMID- 29637813
TI  - Human iPS Cell-based Liver-like Tissue Engineering at Extrahepatic Sites in Mice
      as a New Cell Therapy for Hemophilia B.
AB  - Instead of liver transplantation or liver-directed gene therapy, genetic liver
      diseases are expected to be treated effectively using liver tissue engineering
      technology. Hepatocyte-like cells (HLCs) generated from human-induced pluripotent
      stem (iPS) cells are an attractive unlimited cell source for liver-like tissue
      engineering. In this study, we attempted to show the effectiveness of human iPS
      cell-based liver-like tissue engineering at an extrahepatic site for treatment of
      hemophilia B, also called factor IX (FIX) deficiency. HLCs were transplanted
      under the kidney capsule where the transplanted cells could be efficiently
      engrafted. Ten weeks after the transplantation, human albumin (253 MUg/mL) and
      alpha-1 antitrypsin (1.2 MUg/mL) could be detected in the serum of transplanted
      mice. HLCs were transplanted under the kidney capsule of FIX-deficient mice. The
      clotting activities in the transplanted mice were approximately 5% of those in
      wild-type mice. The bleeding time in transplanted mice was shorter than that in
      the nontransplanted mice. Taken together, these results indicate the success in
      generating functional liver-like tissues under the kidney capsule by using human
      iPS cell-derived HLCs. We also demonstrated that the human iPS cell-based liver
      like tissue engineering technology would be an effective treatment of genetic
      liver disease including hemophilia B.

PMID- 29637811
TI  - Causes and consequences of genomic instability in laminopathies: Replication
      stress and interferon response.
AB  - Mammalian nuclei are equipped with a framework of intermediate filaments that
      function as a karyoskeleton. This nuclear scaffold, formed primarily by lamins (A
      type and B-type), maintains the spatial and functional organization of the genome
      and of sub-nuclear compartments. Over the past decade, a body of evidence has
      highlighted the significance of these structural nuclear proteins in the
      maintenance of nuclear architecture and mechanical stability, as well as genome
      function and integrity. The importance of these structures is now unquestioned
      given the wide range of degenerative diseases that stem from LMNA gene mutations,
      including muscular dystrophy disorders, peripheral neuropathies, lipodystrophies,
      and premature aging syndromes. Here, we review our knowledge about how
      alterations in nuclear lamins, either by mutation or reduced expression, impact
      cellular mechanisms that maintain genome integrity. Despite the fact that DNA
      replication is the major source of DNA damage and genomic instability in dividing
      cells, how alterations in lamins function impact replication remains minimally
      explored. We summarize recent studies showing that lamins play a role in DNA
      replication, and that the DNA damage that accumulates upon lamins dysfunction is
      elicited in part by deprotection of replication forks. We also discuss the
      emerging model that DNA damage and replication stress are "sensed" at the
      cytoplasm by proteins that normally survey this space in search of foreign
      nucleic acids. In turn, these cytosolic sensors activate innate immune responses,
      which are materializing as important players in aging and cancer, as well as in
      the response to cancer immunotherapy.

PMID- 29637814
TI  - A PEG-Based Hydrogel for Effective Wound Care Management.
AB  - It is extremely challenging to achieve strong adhesion in soft tissues while
      minimizing toxicity, tissue damage, and other side effects caused by wound
      sealing materials. In this study, flexible synthetic hydrogel sealants were
      prepared based on polyethylene glycol (PEG) materials. PEG is a synthetic
      material that is nontoxic and inert and, thus, suitable for use in medical
      products. We evaluated the in vitro biocompatibility tests of the dressings to
      assess cytotoxicity and irritation, sensitization, pyrogen toxicity, and systemic
      toxicity following the International Organization for Standardization 10993
      standards and the in vivo effects of the hydrogel samples using Coloskin liquid
      bandages as control samples for potential in wound closure.

PMID- 29637815
TI  - The Effect of Tissue Preparation and Donor Age on Striatal Graft Morphology in
      the Mouse.
AB  - Huntington's disease (HD) is a progressive neurodegenerative disease in which
      striatal medium spiny neurons (MSNs) are lost. Neuronal replacement therapies aim
      to replace MSNs through striatal transplantation of donor MSN progenitors, which
      successfully improve HD-like deficits in rat HD models and have provided
      functional improvement in patients. Transplants in mouse models of HD are more
      variable and have lower cell survival than equivalent rat grafts, yet mice
      constitute the majority of transgenic HD models. Improving the quality and
      consistency of mouse transplants would open up access to this wider range of
      rodent models and facilitate research to increase understanding of graft
      mechanisms, which is essential to progress transplantation as a therapy for HD.
      Here we determined how donor age, cell preparation, and donor/host strain choice
      influenced the quality of primary embryonic grafts in quinolinic acid lesion
      mouse models of HD. Both a within-strain (W-S) and a between-strain (B-S)
      donor/host paradigm were used to compare transplants of donor tissues derived
      from mice at embryonic day E12 and E14 prepared either as dissociated suspensions
      or as minimally manipulated tissue pieces (TP). Good graft survival was observed,
      although graft volume and cellular composition were highly variable. The effect
      of cell preparation on grafts differed significantly depending on donor age, with
      E14 cell suspensions yielding larger grafts compared to TP. Conversely, TP were
      more effective when derived from E12 donor tissue. A W-S model produced larger
      grafts with greater MSN content, and while high levels of activated microglia
      were observed across all groups, a greater number was found in B-S transplants.
      In summary, we show that the effect of tissue preparation on graft morphology is
      contingent on the age of donor tissue used. The presence of microglial activation
      in all groups highlights the host immune response as an important consideration
      in mouse transplantation.

PMID- 29637816
TI  - Cardiotrophic Growth Factor-Driven Induction of Human Muse Cells Into
      Cardiomyocyte-Like Phenotype.
AB  - Multilineage-differentiating stress-enduring (Muse) cells are endogenous
      nontumorigenic stem cells collectable as stage-specific embryonic antigen 3 (SSEA
      3) + from various organs including the bone marrow and are pluripotent-like. The
      potential of human bone marrow-derived Muse cells to commit to cardiac lineage
      cells was evaluated. We found that (1) initial treatment of Muse cells with 5'
      azacytidine in suspension culture successfully accelerated demethylation of
      cardiac marker Nkx2.5 promoter; (2) then transferring the cells onto adherent
      culture and treatment with early cardiac differentiation factors including
      wingless-int (Wnt)-3a, bone morphogenetic proteins (BMP)-2/4, and transforming
      growth factor (TGF) beta1; and (3) further treatment with late cardiac
      differentiation cytokines including cardiotrophin-1 converted Muse cells into
      cardiomyocyte-like cells that expressed alpha-actinin and troponin-I with a
      striation-like pattern. MLC2a expression in the final step suggested
      differentiation of the cells into an atrial subtype. MLC2v, a marker for a mature
      ventricular subtype, was expressed when cells were treated with Dickkopf-related
      protein 1 (DKK-1) and Noggin, inhibitors of Wnt3a and BMP-4, respectively,
      between steps (2) and (3). None of the steps included exogenous gene
      transfection, making induced cells feasible for future clinical application.

PMID- 29637818
TI  - Effect of Cinnamomum osmophloeum Kanehira Leaf Aqueous Extract on Dermal Papilla
      Cell Proliferation and Hair Growth.
AB  - In this study, we explored the effect of the water extract of Cinnamomum
      osmophloeum Kanehira (COK) leaves on hair growth by in vitro and in vivo assays.
      Using an in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide
      (MTT) assay, it was found that the proliferation of rat vibrissae and human hair
      dermal papilla cells (hDPCs) was significantly enhanced by the COK leaf extract
      treatment. As determined by quantitative real-time polymerase chain reaction (RT
      PCR), the messenger RNA (mRNA) levels of some hair growth-related factors
      including vascular endothelial growth factor, keratinocyte growth factor (KGF),
      and transforming growth factor-beta2 were found to be higher in the cultured
      hDPCs exposed to COK leaf extract than those in the untreated control group. In
      the hair-depilated C57BL/6 mouse model, the stimulation of hair growth was
      demonstrated in the group of COK leaf extract treatment. Both photographical and
      histological observations revealed the promotion of the anagen phase in the hair
      growth cycle by the COK leaf extract in the C57BL/6 mice. Finally, the ultra
      performance liquid chromatography (UPLC) showed that the COK extract contained
      mostly cinnamic aldehyde and a small amount of cinnamic acid. The results suggest
      that the COK leaf extract may find use for the treatment of hair loss.

PMID- 29637820
TI  - A Randomized, Placebo-Controlled Trial of Human Umbilical Cord Blood Mesenchymal
      Stem Cell Infusion for Children With Cerebral Palsy.
AB  - Cerebral palsy (CP) is a common disability which results in permanent chronic
      motor disability appearing in early childhood. Recently human umbilical cord
      blood mesenchymal stem cell (hUCB-MSC) infusion has emerged as a promising
      therapeutic strategy for CP, and the treatment efficacy remains to be confirmed
      by clinical trials. All 54 patients received basic rehabilitation as a background
      treatment. The infusion group comprising 27 patients received 4 infusions of hUCB
      MSCs (intravenous infusions at a fixed dose of 5 * 107) and basic rehabilitation
      treatment, whereas 27 patients in the control group received 0.9% normal saline
      and basic rehabilitation treatment. Several indices were tested from baseline up
      to 24 months posttreatment regarding efficacy and safety evaluations, including
      the gross motor function measurement 88 (GMFM-88) scores, the comprehensive
      function assessment (CFA), lab tests, electroencephalogram (EEG), routine
      magnetic resonance imaging (MRI), and adverse events. The changes in the total
      proportion of GMFM-88 and total scores of CFA in the hUCB-MSC infusion group were
      significantly higher than that in control group at 3, 6, 12, 24 months
      posttreatment. Less diffuse slow waves were noticed after hUCB-MSC infusion in
      patients with slowing of EEG background rhythms at baseline. Based on the routine
      MRI exams, improvements in cerebral structures were rare after treatment. Serious
      adverse events were not observed during the whole study period. The results of
      the study indicated that hUCB-MSC infusion with basic rehabilitation was safe and
      effective in improving gross motor and comprehensive functions in children with
      CP.

PMID- 29637819
TI  - Methods to Induce Chronic Ocular Hypertension: Reliable Rodent Models as a
      Platform for Cell Transplantation and Other Therapies.
AB  - Glaucoma, a form of progressive optic neuropathy, is the second leading cause of
      blindness worldwide. Being a prominent disease affecting vision, substantial
      efforts are being made to better understand glaucoma pathogenesis and to develop
      novel treatment options including neuroprotective and neuroregenerative
      approaches. Cell transplantation has the potential to play a neuroprotective
      and/or neuroregenerative role for various ocular cell types (e.g., retinal cells,
      trabecular meshwork). Notably, glaucoma is often associated with elevated
      intraocular pressure, and over the past 2 decades, several rodent models of
      chronic ocular hypertension (COH) have been developed that reflect these changes
      in pressure. However, the underlying pathophysiology of glaucoma in these models
      and how they compare to the human condition remains unclear. This limitation is
      the primary barrier for using rodent models to develop novel therapies to manage
      glaucoma and glaucoma-related blindness. Here, we review the current techniques
      used to induce COH-related glaucoma in various rodent models, focusing on the
      strengths and weaknesses of the each, in order to provide a more complete
      understanding of how these models can be best utilized. To so do, we have
      separated them based on the target tissue (pre-trabecular, trabecular, and post
      trabecular) in order to provide the reader with an encompassing reference
      describing the most appropriate rodent COH models for their research. We begin
      with an initial overview of the current use of these models in the evaluation of
      cell transplantation therapies.

PMID- 29637821
TI  - Orthotopic Transplantation of Achilles Tendon Allograft in Rats: With or without
      Incorporation of Autologous Mesenchymal Stem Cells.
AB  - The biology and function of orthotopic transplantation of Achilles tendon
      allograft are unknown. Particularly, the revitalization of Achilles allograft is
      a clinical concern. Achilles allografts were harvested from donor rats and stored
      at -80  degrees C. Subcutaneous adipose tissue was harvested from the would-be
      allograft recipient rats for isolation of mesenchymal stem cells (MSCs). MSCs
      were cultured with growth differentiation factor-5 (GDF-5) and applied onto
      Achilles allografts on the day of transplantation. After the native Achilles
      tendon was resected from the left hind limb of the rats, Achilles allograft, with
      or without autologous MSCs, was implanted and sutured with calf muscles
      proximally and calcaneus distally. Animal gait was recorded presurgery and
      postsurgery weekly. The animals were sacrificed at week 4, and the transplanted
      Achilles allografts were collected for biomechanical testing and histology. The
      operated limbs had altered gait. By week 4, the paw print intensity, stance time,
      and duty cycle (percentage of the stance phase in a step cycle) of the
      reconstructed limbs were mostly recovered to the baselines recorded before
      surgery. Maximum load of failure was not different between Achilles allografts,
      with or without MSCs, and the native tendons. The Achilles allograft supplemented
      with MSCs had higher cellularity than the Achilles allograft without MSCs.
      Deposition of fine collagen (type III) fibers was active in Achilles allograft,
      with or without MSCs, but it was more evenly distributed in the allografts that
      were incubated with MSCs. In conclusion, orthotopically transplanted Achilles
      allograft healed with host tissues, regained strength, and largely restored
      Achilles function in 4 wk in rats. It is therefore a viable option for the
      reconstruction of a large Achilles tendon defect. Supplementation of MSCs
      improved repopulation of Achilles allograft, but large animal models, with long
      term follow up and cell tracking, may be required to fully appreciate the
      functional benefits of MSCs.

PMID- 29637823
TI  - What is in a name?

PMID- 29637822
TI  - Handling properties of a superabsorbent dressing in the management of patients
      with moderate-to-very high exuding wounds.
AB  - OBJECTIVE: Exudate control is an important aspect of wound management in both
      acute and chronic wounds. Exudate can be an indicator of the wound bed condition,
      specifically inflammation and infection. This study aimed to evaluate the
      performance, in terms of usability, handling properties, exudate management, user
      satisfaction and patient comfort, in daily clinical practice, of a superabsorbent
      dressing, Vliwasorb Pro (Lohmann & Rauscher), suitable for the management of
      moderate-to-very high exudate levels. METHOD: The user test was conducted between
      September 2016 and July 2017, with clinicians from different specialisms in 55
      centres across Germany. Both the dressing and user test were supplied by the
      sponsor. The superabsorbent dressing was used for at least three dressing
      changes, with frequency dependent on the patient and wound condition. RESULTS: A
      total of 55 clinicians recruited 171 patients with various wound types. The
      clinicians rated dressing application as 'easy' for 163 (95.3%) of the patients.
      The dressing was rated as easy to remove (168 (98.3%) and, according to
      clinicians, did not soil patients' clothing in 165 (97.1%) of cases. The dressing
      demonstrated a 'good absorbent capacity', as noted by clinicians in 167 (98.2%)
      of cases. Clinicians also commented that the dressing reduced foul odour,
      maceration and improved periwound skin condition. CONCLUSION: The evaluated
      dressing was easy to use, comfortable and reliable for patients with moderate-to
      very high exuding wounds. In view of these results, superabsorbent dressings seem
      to be interesting for both clinicians and patients. Clinical studies are required
      to confirm these results.

PMID- 29637824
TI  - Cost-effectiveness of an electroceutical device in treating non-healing venous
      leg ulcers: results of an RCT.
AB  - OBJECTIVE: To estimate the cost-effectiveness of an externally applied
      electroceutical (EAE) device, Accel-Heal, in treating non-healing venous leg
      ulcers (VLUs) in the UK. METHOD: This was a prospective, randomised, double
      blind, placebo-controlled, multi-centre study of patients aged >=18 years with a
      non-healing VLU. Patients were randomised in the ratio of 1:1 to receive six
      units of the EAE (consisting of a self-contained, programmed electric
      microcurrent generator and two skin contact pads) or an identical-looking placebo
      device over 12 consecutive days. Patients were followed-up for 24 weeks from
      randomisation, during which time patients received wound care according to the
      local standard care pathway, completed health-related quality of life (HRQoL)
      instruments, and health-care resource use was measured. The cost-effectiveness of
      the EAE device was estimated at 2015/16 prices in those patients who fulfilled
      the study's inclusion and exclusion criteria (economic analysis population).
      RESULTS: At 24 weeks after randomisation, 34% and 30% of VLUs in the EAE and
      placebo groups in the economic analysis population, respectively, had healed. The
      time-to-healing was a mean of 2.6 and 3.5 months in the EAE and placebo groups,
      respectively. The area of the wounds that healed in the EAE group was nearly
      twice that of those in the placebo group (mean: 13.3 versus 7.7cm2 per VLU).
      Additionally, the pre-randomised duration of the wounds that healed in the EAE
      group was double that of those in the placebo group (mean: 2.6 versus 1.2 years
      per VLU). By the end of the study, EAE-treated patients reported less pain, more
      social functioning and greater overall wellbeing/satisfaction than placebo
      treated patients. None of these differences reached statistical significance, but
      they may be important to patients. There were no significant differences in
      health-care resource use between the two groups. The incremental cost per quality
      adjusted life year (QALY) gained with the EAE device was L4480 at eight weeks,
      decreasing to L2265 at 16 weeks and -L2388 (dominant) at 24 weeks. The study was
      confounded by unwarranted variation in patient management between centres and
      between individual clinicians within each centre. CONCLUSION: Despite the
      unwarranted variation in the provision of wound care observed in this study, the
      use of the EAE device resulted in some improved clinical outcomes and patient
      reported outcomes, for the same or less cost as standard care, by 24 weeks.
      Clinicians managing VLUs may wish to consider the findings from this study when
      making treatment decisions.

PMID- 29637825
TI  - Erratum.

PMID- 29637826
TI  - A warm welcome for wound care specialists in Abu Dhabi.

PMID- 29637827
TI  - Biological wound matrices with native dermis-like collagen efficiently modulate
      protease activity.
AB  - OBJECTIVE: When the delicate balance between catabolic and anabolic processes is
      disturbed for any reason, the healing process can stall, resulting in chronic
      wounds. In chronic wound pathophysiology, proteolytic imbalance is implicated due
      to elevated protease levels mediating tissue damage. Hence, it is important to
      design appropriate wound treatments able to control and modulate protease
      activity directly at the host/biomaterial interface. Here, we investigate
      collagen-based wound dressings with the focus on their potential to adsorb and
      inactivate tissue proteases. METHOD: We examined the effect of six collagen-based
      dressings on their ability to adsorb and inactivate different granulocyte
      proteases, plasmin, human neutrophil elastase (HLE), and matrix metalloproteases
      (MMP)-1, -2, -8, and -9, by an integrated approach including immunoelectron
      microscopy. RESULTS: We observed a reduction of the proteolytic activities of
      plasmin, HLE, and MMP-1, -2, -8, and -9, both on the biomaterial surface and in
      human chronic wound fluid. The most pronounced effect was observed in collagen
      based dressings, with the highest content of native collagen networks resembling
      dermis structures. CONCLUSION: Our data suggest that this treatment strategy
      might be beneficial for the chronic wound environment, with the potential to
      promote improved wound healing.

PMID- 29637828
TI  - Assessment of clinical effectiveness of haemoglobin spray as adjunctive therapy
      in the treatment of sloughy wounds.
AB  - OBJECTIVE: To assess use of an adjunctive topical haemoglobin spray in the
      treatment of sloughy wounds. METHOD: In addition to a standard wound care
      regimen, consecutive patients with sloughy wounds self-administered haemoglobin
      spray treatment twice a week until the wound was healed. All patients were
      followed-up for 26 weeks. Results were compared with a retrospective cohort of
      100 consecutive patients, treated during the same period the previous year with
      standard wound care alone. Data were collected on wound characteristics including
      percentage of slough, exudate levels, wound pain, and wound size. RESULTS: After
      26 weeks, 94/100 patients (94%) treated with haemoglobin spray were completely
      healed compared with 63/100 control patients (63%). Positive results were evident
      as early as week one with 52% mean wound size reduction using the heamoglobin
      spray versus 11% in the retrospective control (p<0.001). At baseline, mean slough
      coverage was higher in the haemoglobin group, 58% versus 44% in the control group
      (p<0.001). By week four, mean slough coverage was 1% in the haemoglobin versus
      29% in the control group (p<0.001). Reductions in exudate and pain levels
      (p<0.001) were also observed. CONCLUSION: Overall, results of this evaluation
      showed the addition of adjunctive haemoglobin spray to standard wound care
      treatment achieved positive clinical outcomes for patients self-managing
      complicated sloughy wounds, by supporting reduction of wound exudate and slough
      within the complex multifaceted process of wound healing.

PMID- 29637830
TI  - Erratum.

PMID- 29637829
TI  - An evaluation of an ultrasonic debridement system in patients with diabetic foot
      ulcers: a case series.
AB  - OBJECTIVE: This study evaluated the use of ultrasonic debridement in patients
      with diabetic foot ulcers (DFU). METHOD: In this prospective, single-arm, open
      label study, all patients with DFUs underwent wound debridement by ultrasonic
      debridement system (SonicOne OR Ultrasonic debridement system). Wherever
      possible, the edges were approximated by means of stitches. In other cases, the
      surgical breach healed by secondary intention, or a partial thickness skin graft
      (with or without Integra Dermal Regeneration Template or Integra Flowable Wound
      Matrix) was applied, and subsequently healed by primary intention. RESULTS: We
      assessed 15 patients with a DFU. The time required for debridement was short (an
      average 15.06+/-4.02 minutes). Complete wound healing (defined as 100% re
      epithelialisation) was achieved in all 15 cases. Median time to heal was 39.20+/
      16.05 days. The ultrasonic debridement system was found to show adequate
      debridement while preserving more viable tissue to promote rapid healing.
      CONCLUSION: Our findings show that the device demonstrates advantages in the
      reduction of debridement times, and efficacy in safely preserving the viable
      tissue, with a low complication rate in surgery of DFUs. A study that uses a
      larger cohort is required to fully evaluate the effectiveness, or otherwise, of
      the ultrasonic debridement system.

PMID- 29637817
TI  - Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017).
AB  - Cell therapy has been shown to be a key clinical therapeutic option for central
      nervous system diseases or damage. Standardization of clinical cell therapy
      procedures is an important task for professional associations devoted to cell
      therapy. The Chinese Branch of the International Association of
      Neurorestoratology (IANR) completed the first set of guidelines governing the
      clinical application of neurorestoration in 2011. The IANR and the Chinese
      Association of Neurorestoratology (CANR) collaborated to propose the current
      version "Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017)".
      The IANR council board members and CANR committee members approved this proposal
      on September 1, 2016, and recommend it to clinical practitioners of cellular
      therapy. These guidelines include items of cell type nomenclature, cell quality
      control, minimal suggested cell doses, patient-informed consent, indications for
      undergoing cell therapy, contraindications for undergoing cell therapy,
      documentation of procedure and therapy, safety evaluation, efficacy evaluation,
      policy of repeated treatments, do not charge patients for unproven therapies,
      basic principles of cell therapy, and publishing responsibility.

PMID- 29637831
TI  - Extracorporeal membrane oxygenation: Establishing a robust, tertiary
      extracorporeal membrane oxygenation referral center in South Florida.

PMID- 29637832
TI  - Maximum level of mobility with axillary deployment of the Impella 5.0 is
      associated with improved survival.
AB  - Mobility is an important prognostic indicator for patients with cardiogenic
      shock. No studies have quantified peak mobility for patients with cardiogenic
      shock who are supported with the Impella 5.0 acute mechanical circulatory support
      device. The purpose of our study was to evaluate mobility levels among patients
      with cardiogenic shock being treated with an axillary Impella 5.0 pump. We
      retrospectively analyzed data from 19 patients receiving an Impella 5.0 device
      for cardiogenic shock at our institution from 2013 to 2016. We used the Johns
      Hopkins Highest Level of Mobility Scale to quantify maximum mobility level
      achieved during active Impella 5.0 support. Higher scores on a scale of 1-8
      indicated more mobility. Activity Measure for Post Acute Care Scores were
      quantified for each patient to assess activity limitations, with a maximum score
      24. The mean age of the total cohort was 60 +/- 12 years, and the mean left
      ventricular ejection fraction was 16% +/- 6%. In-hospital mortality was 47% (n =
      9). Of the 19 Impella 5.0 implants, 10 survived, 6 died from withdrawal of care,
      and 3 died from worsening heart failure/cardiogenic shock. Similar rates of
      mobilization during the time of Impella implant were seen between groups.
      Compared to non-survivors, survivors achieved a higher maximum Johns Hopkins
      Highest Level of Mobility level, but similar Activity Measure for Post Acute Care
      scores. In conclusion, maximum mobility after Impella 5.0 implantation may be
      associated with improved survival. The clinical utility of exercise as a
      therapeutic intervention for patients requiring prolonged acute mechanical
      circulatory support requires further study.

PMID- 29637833
TI  - Polysaccharide-based hydrogels with tunable composition as 3D cell culture
      systems.
AB  - BACKGROUND: To date, cell cultures have been created either on 2-dimensional (2D)
      polystyrene surfaces or in 3-dimensional (3D) systems, which do not offer a
      controlled chemical composition, and which lack the soft environment encountered
      in vivo and the chemical stimuli that promote cell proliferation and allow
      complex cellular behavior. In this study, pectin-based hydrogels were developed
      and are proposed as versatile cell culture systems. METHODS: Pectin-based
      hydrogels were produced by internally crosslinking pectin with calcium carbonate
      at different initial pH, aiming to control crosslinking kinetics and degree.
      Additionally, glucose and glutamine were added as additives, and their effects on
      the viscoelastic properties of the hydrogels and on cell viability were
      investigated. RESULTS: Pectin hydrogels showed in high cell viability and shear
      thinning behavior. Independently of hydrogel composition, an initial swelling was
      observed, followed by a low percentage of weight variation and a steady-state
      stage. The addition of glucose and glutamine to pectin-based hydrogels rendered
      higher cell viability up to 90%-98% after 1 hour of incubation, and these
      hydrogels were maintained for up to 7 days of culture, yet no effect on
      viscoelastic properties was detected. CONCLUSIONS: Pectin-based hydrogels that
      offer tunable composition were developed successfully. They are envisioned as
      synthetic extracellular matrix (ECM) either to study complex cellular behaviors
      or to be applied as tissue engineering substitutes.

PMID- 29637834
TI  - Intraductal Papillary Mucinous Neoplasms of The Pancreas: A Nationwide Registry
      Based Study.
AB  - BACKGROUND AND AIMS:: To investigate the paraclinical and pathological features
      of surgically resected intraductal papillary mucinous neoplasms in Sweden.
      MATERIALS AND METHODS:: A review of prospectively collected data on patients
      undergoing pancreatic resection for a histopathologically verified intraductal
      papillary mucinous neoplasm between 2010 and 2016 was performed using the Swedish
      National Registry for Pancreatic and Periampullary Cancer. RESULTS:: A total of
      3038 pancreatic resections were performed during the study period, of which 251
      (8.3%) were due to intraductal papillary mucinous neoplasms. The intraductal
      papillary mucinous neoplasm cases comprised 227 noninvasive and 24 invasive
      lesions. There was an annual increase in the number of resected intraductal
      papillary mucinous neoplasms, from 13 in 2010 to 56 in 2016, and an increase in
      the proportion of intraductal papillary mucinous neoplasm to the total number of
      pancreatic resections (4.7%-11%). Biliary obstruction was the only independent
      predictor of invasive disease, with odds ratio 3.106 (p = 0.030). There was no
      difference in survival between low-, intermediate-, and high-grade dysplastic
      lesions (p = 0.417). However, once invasive, the prognosis was severely impacted
      (p < 0.001). Three-year survival was 90% for noninvasive intraductal papillary
      mucinous neoplasm and 39% for invasive intraductal papillary mucinous neoplasm.
      Survival was better in lymph node negative invasive intraductal papillary
      mucinous neoplasm (p = 0.021), but still dismal compared to noninvasive lesions
      (p < 0.001). CONCLUSION:: The number of surgically resected intraductal papillary
      mucinous neoplasms is increasing in Sweden. Biliary obstruction is associated
      with invasive disease. Low-to-high-grade dysplastic intraductal papillary
      mucinous neoplasm has an excellent prognosis, while invasive intraductal
      papillary mucinous neoplasm has a poor survival rate.

PMID- 29637835
TI  - Physical employment standard for Canadian wildland fire fighters; identifying and
      characterising critical initial attack response tasks.
AB  - Physical employment standards evaluate whether a worker possesses the physical
      abilities to safely and efficiently perform all critical on-the-job tasks.
      Initial Attack (IA) wildland fire fighters (WFF) must perform such critical tasks
      in all terrains. Following a physical demands analysis, IA WFF (n = 946 out of a
      possible 965) from all fire jurisdictions ranked the most demanding tasks and
      identified mountains, muskeg and rolling hills as the most challenging terrains.
      Experimental trials found the oxygen cost (mean +/- SD [Formula: see text]O2
      mL.kg-1.min-1) while performing the hose pack back carry to be 40 +/- 7 in steep
      mountains, 34 +/- 5 in muskeg and 34 +/- 2 in rolling hills (n = 168). Back
      carrying and hand-carrying a 28.5 kg pump, back-carrying a 25 kg hose pack and
      advancing charged hose were the most demanding tasks. Performing the same
      emergency IA WFF tasks was significantly more demanding in mountains (p <= 0.05),
      and these higher demands must be taken into account when developing a physical
      employment standard for Canadian wildland fire fighters. Practitioner Summary:
      Physical employment standards evaluate whether an applicant or incumbent
      possesses the physical and physiological abilities to safely and efficiently
      perform the critical on-the-job tasks. This paper details the process used to
      undertake a physical demands analysis and characterise tasks for the development
      of a  circuit test and fitness employment standard for IA WFF.

PMID- 29637836
TI  - Recommendations to maintain immune health in athletes.
AB  - Numerous studies over the last 35 years report an increase in upper respiratory
      infection (URI) symptoms in athletes during periods of heavy training and
      competition. Challenges athletes face such as heavy exercise and life stress
      influence immune function via activation of the hypothalamic-pituitary-adrenal
      axis and the sympathetic nervous system and the resulting immunoregulatory
      hormones. Both innate and acquired immunity are often reported to decrease
      transiently in the hours after heavy exertion, typically 15-70%: prolonged heavy
      training sessions in particular have been shown to decrease immune function;
      potentially providing an 'open window' for opportunistic infections. Whether the
      observed changes in immunity with acute strenuous exercise or periods of heavy
      training account for the increased susceptibility to URI symptoms remains
      contentious. Nevertheless, there is little doubt that URI symptoms hinder
      athletic training and competition; underpinning the need to identify the
      prominent risk factors and appropriate countermeasures. Recent studies have
      identified prominent risk factors, including: intensified training in the winter;
      long-haul travel; low energy availability; high levels of psychological stress
      and anxiety; and depression. Given the shared pathways and effector limbs for the
      body's response to physical and psychological challenges, it is logical that
      psychological strain influences immunity and illness incidence in athletes under
      heavy training; indeed, stress and anxiety have recently been shown to modify the
      immune response to exercise. This mini-review provides new insights and evidence
      based recommendations for coping with the various challenges that athletes
      encounter on immune health, including: heavy exercise; life stress; sleep
      disruption; environmental extremes and nutritional deficits.

PMID- 29637837
TI  - Does dental appearance affect employment prospects: a prospective cross-sectional
      study.
AB  - OBJECTIVE: The principal aim was to establish whether dental appearance affects
      employment prospects, and if so a secondary aim was to ascertain whether there is
      a difference between public-facing and non-public-facing jobs. DESIGN: A
      prospective cross-sectional experimental analogue study. PARTICIPANTS: Ninety
      undergraduates studying at London Metropolitan University School of Business.
      METHODS: Vignettes comprising curriculum vitae (CV) with a single photograph of
      the applicant attached formed the experimental manipulation. For each job
      application, the written information on the CV remained constant, but the
      attached photograph had one of three altered dental appearances: (1) aligned
      teeth, (2) maxillary stainless steel labial fixed appliance and (3) an absent
      maxillary left lateral incisor. To ascertain whether there are differences
      between public- and non-public-facing jobs, two different job descriptions with
      matching CVs were designed. Each participant was randomly assigned an envelope
      containing one CV with one photograph and asked if they would shortlist the
      candidate for an interview. Likert scales were used with higher scores indicating
      greater likelihood to shortlist. A Multivariate Analysis of Variance was
      conducted with Photo (three levels) and Job Type (two levels) as independent
      variables, and gender as a covariate. RESULTS: A trend was found for the
      candidate with an absent maxillary lateral incisor to be less likely to be
      shortlisted for the public-facing job, compared to both candidates with aligned
      teeth and with fixed appliances. There were no significant main effects and the
      interaction was not significant. The effect of gender was not significant.
      CONCLUSIONS: In this study, dental appearance did not influence employment
      prospects. When a photograph is attached to a CV, the dental appearance of the
      photograph did not influence whether a candidate was shortlisted for a job
      interview or their anticipated job performance. There were no differences between
      public-facing and non-public-facing jobs.

PMID- 29637838
TI  - Clinical reappraisal and state of the art of nephropexy.
AB  - The diffusion of minimally invasive techniques for renal surgery has prompted a
      renewed interest in nephropexy which is indicated to prevent nephroptosis in
      symptomatic patients and to mobilize the upper ureter downward in order to bridge
      a ureteral defect. Recent publications have been reviewed to present the state of
      the art of the diagnosis and management of these two challenging conditions and
      to try to foresee the next steps. The evaluation of patients with mobile kidney
      can be made relying on diagnostic criteria such as ultrasound with color Doppler
      and measurement of resistive index, conventional upright X-ray frames after a
      supine uro-computerized tomography scan and both static and dynamic nuclear
      medicine scans, always with evaluation in the sitting or erect position.
      Laparoscopic nephropexy emerges as the current treatment option combining both
      objectively controlled repositioning of the kidney and resolution of symptoms
      with minimal invasiveness, low morbidity, and short hospital stay. The use of
      robotics is presently limited by its higher cost, but may increase in the future.
      Downward renal mobilization and nephropexy is a safe and versatile technique
      which has been adopted as a unique strategy or more often in combination with
      other surgical maneuvers in order to cope with complex ureteral reconstruction.

PMID- 29637839
TI  - Risk factors to predict leg ischemia in patients undergoing single femoral artery
      cannulation in minimally invasive cardiac surgery.
AB  - BACKGROUND: In peripheral cannulation for cardiopulmonary bypass, there is always
      a risk of ischemia in the extremities, caused by femoral artery cannulation. This
      report aimed to evaluate the outcome and the risk factors in patients undergoing
      minimally invasive cardiac surgery in mitral valve surgery. METHODS: We
      retrospectively reviewed all minimally invasive mitral valve surgery at our
      institute from May 2014 to December 2016. Operative outcomes and intra-operative
      monitoring for distal leg saturation were measured by the near-infrared
      spectroscopy values. For post-operative outcomes, the creatinine phosphorus
      kinase level was measured for the assessment of leg ischemia. Risk factors were
      evaluated for the elevation of post-operative creatinine phosphorus kinase.
      RESULTS: There were 162 patients who underwent single femoral artery cannulation
      for minimally invasive mitral valve surgery. The mean operation, cardiopulmonary
      bypass and aortic cross-clamp time were 212+/-44, 124+/-30, 76.6+/-22 minutes
      (min), respectively. The factors related to increased creatinine phosphorus
      kinase were male, body mass index, larger cannula size, operation time,
      cardiopulmonary bypass time and aortic cross-clamp time. The measurement of
      minimum near-infrared spectroscopy values did not show any association with
      creatinine phosphorus kinase elevation. There were significant associations
      between body mass index, cannula size and operation time and post-operative
      creatinine phosphorus kinase increase by multiple regression analysis. Two male
      patients had extremely high post-operative creatinine phosphorus kinase (18188
      U/L and 16831 U/L) and they had high body mass index, large cannula size and
      longer operation time. CONCLUSIONS: In peripheral cannulation for minimally
      invasive cardiac surgery, body mass index, cannula size and operation time can be
      considered as risk factors for leg ischemia.

PMID- 29637840
TI  - Albumin priming improves the efficiency of the Minntech HPH Jr. hemoconcentrator.
AB  - The desired use of the HPH Jr. is optimal due to the low priming volume; however,
      the lower rate of volume removal necessitates utilization of a larger hemofilter.
      Larger hemofilters carry a higher prime volume, which is impactful in the
      pediatric setting. Pediatric cardiac surgery patients under 18 kilograms
      requiring cardiopulmonary bypass were randomly assigned to one of two study
      groups. Group 1 (coated) contained an HPH Jr. hemofilter that was primed with the
      addition of 25% albumin and heparin. Group 2 (non-coated) contained an HPH Jr.
      hemofilter that was primed with only Normosol-R(r). After cardioplegia delivery,
      zero balance ultrafiltration (ZBUF) was initiated and maintained for thirty
      consecutive minutes. The flow through the hemofilter was standardized at 70
      ml/min and the vacuum applied to the effluent line was set at -150 mmHg. Effluent
      fluid removal was measured at the termination of thirty minutes and compared
      between the groups. Group comparisons between the coated vs non-coated hemofilter
      groups were assessed using two-sample t-tests or the Mann-Whitney U test, when
      appropriate. Forty-two patients were included in the analysis. There were 22
      patients who had the non-coated hemofilter and 20 patients with a coated
      hemofilter. The differences between the two groups are illustrated in Table 1.
      There was a statistically significant higher ultrafiltration volume with the
      coated hemofilter group (p=0.008) (Figure 1). These results illustrate the
      improved efficiency of the HPH Jr. with the addition of 25% albumin and heparin
      during the priming process.

PMID- 29637841
TI  - Geographical distribution of beta-globin gene mutations in Syria.
AB  - OBJECTIVES: beta-Thalassemia disease is caused by mutations in the beta-globin
      gene. This is considered as one of the common genetic disorders in Syria. The aim
      of this study was to identify the geographical distribution of the beta
      thalassemia mutations in Syria. METHODS: beta-Globin gene mutations were
      characterized in 636 affected patients and 94 unrelated carriers using the
      amplification refractory mutations system-polymerase chain reaction technique and
      DNA sequencing. RESULTS: The study has revealed the presence of 38 beta-globin
      gene mutations responsible for beta-thalassemia in Syria. Important differences
      in regional distribution were observed. IVS-I.110 [G > A] (22.2%), IVS-I.1 [G >
      A] (17.8%), Cd 39 [C > T] (8.2%), IVS-II.1 [G > A] (7.6%), IVS-I.6 [T > C]
      (7.1%), Cd 8 [-AA] (6%), Cd 5 [-CT] (5.6%) and IVS-I.5 [G > C] (4.1%) were the
      eight predominant mutations found in our study. The coastal region had higher
      relative frequencies (37.9 and 22%) than other regions. A clear drift in the
      distribution of the third common Cd 39 [C > T] mutation in the northeast region
      (34.8%) to the northwest region (2.5%) was noted, while the IVS-I.5 [G > C]
      mutation has the highest prevalence in north regions. The IVS-I.6 [T > C]
      mutation had a distinct frequency in the middle region. Ten mutations -86 [C >
      G], -31 [A > G], -29 [A > G], 5'UTR; +22 [G > A], CAP + 1 [A > C], Codon 5/6 [
      TG], IVS-I (-3) or codon 29 [C > T], IVS-I.2 [T > A], IVS-I.128 [T > G] and IVS
      II.705 [T > G] were found in Syria for the first time. CONCLUSIONS: These data
      will significantly facilitate the population screening, genetic counseling and
      prenatal diagnosis in Syrian population.

PMID- 29637842
TI  - Dissecting intramyocardial hematoma with flexuous channel in myocardium
      masquerading as a ventricular pseudoaneurysm.
AB  - We report a 58-year-old acute myocardial infarction patient with dissecting
      intramyocardial hematoma (DIH) disguised as a ventricular pseudoaneurysm. DIH
      with a flexuous and narrow channel in the myocardium was confirmed during the
      operation, which extended deeply into the periphery of the ventricular wall. This
      DIH connected with the left ventricle via a narrow-necked flexuous channel of the
      myocardial defect and looked like a bulged sac surrounded by a thin wall of
      myocadium. No pericardium effusion was seen. Based on this report, we believe
      that a DIH has plentiful variety and this specific kind of DIH should be
      differentially diagnosed with pseudoaneurysm.

PMID- 29637843
TI  - Comparison of East and West Survival Nomograms in Turkish Gastric Cancer Patients
      Who Underwent Radical Surgery.
AB  - BACKGROUND AND AIM:: The clinicopathological demonstrations of gastric cancer
      vary widely between Eastern and Western countries. Turkey is situated in Europe
      and Middle East which acts as a bridge between east and west. We aimed to
      validate the two popular nomograms of east and west origin by means of patients
      who underwent curative surgery for gastric cancer in our country. MATERIAL AND
      METHODS:: Of the 202 patients diagnosed with gastric cancer between the years
      2006 and 2013, 145 of these patients whose data were sufficient were included in
      the study. For all patients, demographic, laboratory, operative, and pathologic
      findings were documented. For each patient, prognostic factors were incorporated
      into the nomograms for estimating 5-year survival probability. RESULTS:: For a
      Turkish cohort, the western nomogram showed a better discriminative capacity (AUC
      = 0.721, 95% confidence interval 0.637-0.806) and was better calibrated (the
      Hosmer-Lemeshow goodness-of-fit test p = 0.323), as compared to the eastern
      nomogram with AUC = 0.615, 95% confidence interval 0.522-0.708, and p = 0.077,
      respectively. CONCLUSION:: Western nomogram was found to be more effective than
      eastern nomogram in prediction of estimating 5-year survival probability in
      patients with resectable gastric cancer in Turkish population.

PMID- 29637845
TI  - Physical employment standard for Canadian wildland firefighters: examining test
      retest reliability and the impact of familiarisation and physical fitness
      training.
AB  - To assess the impact of repeat performances (familiarisation) plus exercise
      training on completion time for the Ontario Wildland Firefighter (WFF) Fitness
      Test circuit (WFX-FIT), normally active general population participants (n = 145)
      were familiarised to the protocol then randomised into (i) exercise training,
      (ii) circuit only weekly performances or (iii) controls. At Baseline, the WFX-FIT
      pass rate for all groups combined was 11% for females and 73% for males,
      indicating that the Ontario WFX-FIT standard had a possible adverse impact on
      females. Following test familiarisation, mean circuit completion times improved
      by 11.9% and 10.2% for females and males, respectively. There were significant
      improvements in completion time for females (19.8%) and males (16.9%) who
      trained, plus females (12.2%) and males (9.8%) who performed the circuit only,
      while control participants were unchanged. Post training, the pass rate of the
      training group was 80% for females and 100% for males. Practitioner Summary: This
      paper details the impact of familiarisation plus exercise training as
      accommodation to mitigate potential adverse impact on initial attack wildland
      firefighter test performance. The results underscore the importance of test
      familiarisation opportunities and physical fitness training programmes that are
      specific to the demands of the job.

PMID- 29637844
TI  - Iron deficiency anemia referral to the hematologist. Real-world data from Mexico:
      the need for targeted teaching in primary care.
AB  - OBJECTIVES: To determine the referral patterns and etiology of iron deficiency
      anemia (IDA) at an academic hematology center in northeast Mexico. METHODS: We
      included all consecutive outpatients older than 16 years, non-pregnant, with IDA
      diagnosed in the Hematology Service of the Dr. Jose E. Gonzalez University
      Hospital between January 2012 and May 2017. Appropriate data were collected
      retrospectively from the electronic medical record. Data regarding first medical
      contact (primary care physician or hematologist) were compared. RESULTS: One
      hundred fifty-three patients were included in this study. The median age was 43
      years (interquartile range, 35-51) and 85.6% were female; 128 (83.7%) patients
      were seen by a primary care physician before our evaluation. Abnormal uterine
      bleeding (AUB) was the cause of IDA in 76 patients (49.6%), gastrointestinal
      bleeding (GIB) in 31 (20.2%), H. pylori infection in 12 (7.8%), urinary tract
      bleeding in three (1.9%) and malabsorption-syndrome in two (1.3%). The etiology
      remained unknown in 29 (18.9%). The p value was <0.05 between groups according to
      the first medical contact, including frequency of at least one sign or symptom of
      IDA, previous use of iron supplementation and blood transfusion, comorbidities,
      complete blood count at diagnosis, and resolution rates of anemia. CONCLUSION:
      The majority of our IDA patients were referred by another physician. Nearly half
      of the patients with IDA had AUB. IDA remains a diagnostic challenge for first
      contact physicians requiring a targeted educational intervention to improve IDA
      awareness and diagnostic skills.

PMID- 29637846
TI  - Sharing Rare Attitudes Attracts.
AB  - People like others who share their attitudes. Online dating platforms as well as
      other social media platforms regularly rely on the social bonding power of their
      users' shared attitudes. However, little is known about moderating variables. In
      the present work, I argue that sharing rare compared with sharing common
      attitudes should evoke stronger interpersonal attraction among people. In five
      studies, I tested this prediction for the case of shared interests from different
      domains. I found converging evidence that people's rare compared with their
      common interests are especially potent to elicit interpersonal attraction. I
      discuss the current framework's theoretical implications for impression formation
      and impression management as well as its practical implications for improving
      online dating services.

PMID- 29637847
TI  - Commitment Readiness and Relationship Formation.
AB  - The concept of being ready for a relationship is pervasive in popular culture,
      but theoretical and empirical research on readiness is lacking. We offer a
      conceptualization of commitment readiness and provide some of the first empirical
      work examining readiness among single individuals-specifically how this construct
      shapes various aspects of relationship formation. Using data from five
      independent samples of individuals not involved in romantic relationships, we
      first establish that commitment readiness is associated with more interest in
      developing a close romantic relationship (Studies 1a, 1b, 2) and with active
      pursuit of relationship initiation (Study 2). We then test whether readiness
      among single individuals longitudinally predicts both the likelihood of later
      entering a relationship and, ultimately, how committed individuals are to a
      future relationship (Studies 3a, 3b, 3c). Implications of commitment readiness
      specifically, and perceived personal timing more generally, for the social
      psychology of relationships are discussed.

PMID- 29637848
TI  - Pro-Social Goals in Achievement Situations: Amity Goal Orientation Enhances the
      Positive Effects of Mastery Goal Orientation.
AB  - Research has neglected the utility of pro-social goals within achievement
      situations. In this article, four studies demonstrate that amity goal
      orientation, promoting mutual success of oneself together with others, enhances
      the utility of mastery goal orientation. We demonstrate this in longitudinally
      predicting performance (Studies 1 and 2) and in maintaining motivation after a
      disappointing performance (Studies 3 and 4). The studies demonstrate the same
      interaction effect in academic and in work achievement contexts. Specifically,
      whereas amity goal orientation did not predict achievement on its own, it
      enhanced the positive effect of mastery goal orientation. Together, these studies
      establish the importance of amity goal orientation while also advancing our
      understanding of the effects of other achievement goal orientations. We suggest
      future directions in examining the utility of amity goals in other contexts.

PMID- 29637849
TI  - Diverse targeted approaches to battle multidrug resistance in cancer.
AB  - The efficacy of successful cancer therapies is frequently hindered by the
      development of drug resistance in the tumor. The term 'drug resistance' is used
      to illustrate the decreased effectiveness of a drug in curing a disease or
      alleviating the symptoms of the patient. This phenomenon helps tumors to survive
      the damage caused by a specific drug or group of drugs. In this context, studying
      the mechanisms of drug resistance and applying this information to design
      customized treatment regimens can improve therapeutic efficacy as well as the
      curative outcome. Over the years, numerous multidrug resistance (MDR) mechanisms
      have been recognized and tremendous effort has been put into developing agents to
      address them. The integration of data emerging from the elucidation of molecular
      and biochemical pathways and specific tumor-associated factors has shown
      tremendous promise within the oncology community for improving patient outcomes.
      In this review, we provide an overview of the utility of these molecular and
      biochemical signaling processes as well as tumor-associated factors associated
      with MDR, for the rational selection of cancer treatment strategies.

PMID- 29637850
TI  - NAChR alpha4beta2 subtype and their relation with nicotine addiction, cognition,
      depression and hyperactivity disorder.
AB  - BACKGROUND: Neuronal alpha4beta2 nAChRs are receptors involved in the role of
      neurotransmitters regulation and release, and this ionic channel participates in
      biological process of memory, learning and attention. This work aims review the
      structure and functioning of the alpha4beta2 nAChR emphasizing its role in the
      treatment of associated diseases like nicotine addiction and underlying
      pathologies such as cognition, depression and attention-deficit hyperactivity
      disorder. METHODS: The authors realized extensive bibliographic research using
      the descriptors "Nicotine Receptor alpha4beta2" and "cognition", "depression",
      "attention-deficit hyperactivity disorder", besides cross-references of the
      selected articles and after analysis of references in the specific literature.
      RESULTS: As results, it was found 180 relevant articles presenting the main
      molecules with affinity to nAChR alpha4beta2 relating to the cited diseases. The
      alpha4beta2 nAChR subtype is a remarkable therapeutic target since this is the
      most abundant receptor in the central nervous system. CONCLUSION: In summary,
      this review presents perspectives on the pharmacology and therapeutic targeting
      of alpha4beta2 nAChRs for the treatment of cognition and diseases like nicotine
      dependence, depression and attention-deficit hyperactivity disorder.

PMID- 29637851
TI  - 99mTc-labeled small molecules for diagnosis of Alzheimer's disease: Past, recent
      and future perspectives.
AB  - BACKGROUND: Alzheimer's disease (AD) is an age-related progressive
      neurodegenerative disease. Its prominent hallmarks are extracellular deposition
      of beta-amyloids (amyloid plaques), intracellular neurofibrillary tangles (NFT),
      neurodegeneration and finally loss of cognitive function. Hence AD diagnosis in
      the early stage and monitoring of the disease are of great importance. METHODS:
      In this review article, we have reviewed recent efforts for design, synthesis and
      evaluation of 99mTc labeled small molecule for AD imaging purposes. RESULTS:
      These small molecules are including derivatives of Congo red, benzothiazole,
      benzofuran, benzoxazole, naphthalene, biphenyl, chalcone, flavone, aurone,
      stilbene, curcumin, dibenzylideneacetone, quinoxaline and etc. The different
      aspects of 99mTc-labeled small molecules including chemical structure, their
      affinity toward amyloid plaques, BBB permeation and in vivo/vitro stability will
      be discussed. CONCLUSION: The findings of this review confirm the importance of
      99mTc-labeled small molecules for AD imaging. Future studies based on the
      pharmacophore of these designed compounds are needed for improvement of these
      molecules for clinical application.

PMID- 29637852
TI  - Polypharmacology in the treatment of Chagas disease.
AB  - The current treatment of Chagas disease is based on monopharmacology where the
      used drugs have limited efficacy and severe side effects. In order to overcome
      these limitations some tools have been described including development or
      isolation of new drugs, drug repositioning, and polypharmacology. Here we review
      the polypharmacology strategy where compounds belonging to different structural
      chemotypes were combined in order to affect different biochemical pathways of T.
      cruzi parasite. Therefore ergosterol biosynthesis inhibitors, anti-inflammatory
      agents, cardiac dysfunction drugs, trypanothione reductase inhibitors, vitamins,
      between others, were combined looking for new anti-Chagas treatment. Natural
      products were also used in the application of this strategy.

PMID- 29637853
TI  - Dopaminergic neuroprotection with Atremorine in Parkinson's disease.
AB  - Patients with Parkinson's disease (PD) are looking forward to new therapeutic
      strategies that may gradually decelerate the rate of neurodegenerative decline,
      associated with mobility restrictions and related morbidity. Its continuous
      neurodegenerative process, exacerbated by genetic mutations or environmental
      toxins, involves a progressively reduction in the dopamine neurotransmission
      levels, synaptic uptake density, oxidative glucose intake, deficient striatal
      lactate accumulation and chronic inflammation. Over the last decade, novel
      bioproducts have received considerable interest due to their unique potential of
      unifying nutritional, safety and therapeutic natural effects. Some nutraceuticals
      play a crucial role in the control of the signaling transduction pathways in
      neurotransmission and inflammation affected in PD, and some natural compounds can
      beneficially interact with each one of these biological mechanisms to slow down
      disease progression. Atremorine, a novel plant-derived nutraceutical, probably
      with a neuroprotective effect in the dopaminergic neurons of the substantia nigra
      (pars compacta), is a prototype of this new category of bioproducts with
      potential effects in PD. The major focus of this review will be the current
      knowledge and biomedical investigation strategies through a plant-derived
      neuroprotective approach to improve life quality in PD patients, being of
      paramount importance for health providers, caregivers and the patients
      themselves.

PMID- 29637854
TI  - Melatonin and oxidative stress in the diabetic state: clinical implications and
      potential therapeutic applications.
AB  - Circadian rhythms are ubiquitous in biological systems and control metabolic
      processes throughout the body. Misalignment of these circadian rhythms increases
      risk of developing metabolic diseases. Thus, disruption of the circadian system
      has been proven to affect onset of type 2 diabetes mellitus (T2DM). In this
      context, the pineal indoleamine melatonin is a signaling molecule able to entrain
      circadian rhythms. There is mounting evidence that suggests a link between
      disturbances in melatonin production and impaired insulin, glucose, lipid
      metabolism, and antioxidant capacity. Besides, several genetic association
      studies have causally associated various single nucleotide polymorphysms (SNPs)
      of human MT2 receptor with increased risk of developing T2DM. Taken together,
      these data suggest that endogenous as well as exogenous melatonin may influence
      diabetes and associated metabolic disturbances not only by regulating insulin
      secretion, but also by providing protection against reactive oxygen species
      (ROS), since pancreatic beta-cells are very susceptible to oxidative stress due
      to their low antioxidant capacity.

PMID- 29637856
TI  - Fruit Wines Inhibitory Activity Against alpha-Glucosidase.
AB  - BACKGROUND: Fruit wines are well known for their profound health-promoting
      properties including both enzyme activations and inhibitions. They may act
      preventive in regard to diabetes melitus and other chronic diseases. OBJECTIVES:
      Potential alpha-glucosidase inhibitory activity of fruit wines made from
      blueberry, black chokeberry, blackberry, raspberry and sour cherry was the
      subject of this study. METHOD: In order to increase the alcohol content due to
      enriched extraction of total phenolics, sugar was added in the fruit pomace of
      the half of the examined fruit wine samples. RESULTS: Compared with acarbose used
      as a positive control (IC50 = 73.78 ug/mL), all fruit wine samples exhibited
      higher alpha-glucosidase inhibitory activity. Indeed, blueberry wine samples
      stood out, both prepared with IC50 = 24.14 ug/mL, lyophilised extract yield 3.23%
      and without IC50 = 46.39 ug/mL, lyophilised extract yield 2.89% and with addition
      of sugar before fermentation. Chlorogenic acid predominantly contributed to alpha
      glucosidase inhibitory activity of the blueberry, black chokeberry and sour
      cherry wine samples. However, ellagic acid, a potent alpha-glucosidase inhibitor
      possessing a planar structure, only slightly affected the activity of the
      blueberry wine samples, due to the lower concentration. In addition to this,
      molecular docking study of chlorogenic acid pointed out the importance of binding
      energy (-8.5 kcal/mol) for the inhibition of the enzyme. CONCLUSION: In summary,
      fruit wines made from blueberry should be primarily taken into consideration as a
      medicinal food targeting diabetes mellitus type 2 in the early stage, if
      additional studies would confirm their therapeutic potential for the control of
      postprandial hyperglycemia.

PMID- 29637858
TI  - Gene Therapy to Enhance Bone and Cartilage Repair in Orthopaedic Surgery.
AB  - Musculoskeletal conditions are a major public health problem. Approximately 66
      million individuals seek medical attention for a musculoskeletal injury in the
      United States, with current medical costs being estimated at $873 billion
      annually. Despite advances in pharmaceuticals, implant materials and surgical
      techniques, there remains an unmet clinical need for successful treatment of
      challenging musculoskeletal injuries and pathologic conditions, particularly in
      the setting of compromised biological environments. Tissue engineering via gene
      therapy attempts to provide an alternative treatment strategy to address the
      deficits associated with conventional approaches. The transfer of specific target
      genes coding for proteins with therapeutic or regenerative properties to target
      cells and tissues in the disease environment allows for their sustained
      production and release specifically at the site of interest. The increasing
      reports of success with gene therapy-based treatments in the clinical management
      of a variety of diseases provide genuine optimism that similar methods can be
      adapted for mainstream clinical application in musculoskeletal disorders. In
      preclinical studies, gene therapy has been successfully used to treat
      cartilaginous, bone, skeletal muscle, tendon, ligament and intervertebral disk
      injuries. In addition, gene therapy is being assessed in clinical trials for its
      safety and therapeutic potential in osteoarthritis. This review will specifically
      address the clinical potential, preclinical data and future hurdles for gene
      therapy to be a viable clinical entity for the treatment of fracture nonunion and
      difficult bone repair scenarios, articular cartilage repair and osteoarthritis.

PMID- 29637857
TI  - Comprehensive Review on Custodiol-N (HTK-N) and its Molecular Side of Action for
      Organ Preservation.
AB  - BACKGROUND: The later fate of a graft is highly dependent on its initial quality.
      Aside from that the three predominant phases during transplantation (Tx) organ
      retrieval, cold static preservation and reperfusion cause in a direct and
      indirect manner graft injury. There is complex ischemia reperfusion injury (IRI)
      triggered during the whole process of Tx which contributes to further damage of
      the graft. METHODS: The today's organ preservation with commercially available
      solutions that all have toxic potential per se is still imperfect. Thus, improved
      preservation solutions are desperately needed to be able to even safely preserve
      grafts from extended criteria donors which are more susceptible to especially
      IRI. Most recently, a modified less toxic histidine-tryptophan-ketoglutarate
      (HTK; Custodiol(r)) the so called histidine-tryptophan-ketoglutarate-N (HTK-N)
      for both better cardioplegia and organ preservation for Tx has been developed. It
      is characterized as an electrolyte balanced, iron chelatorsupplemented, and amino
      acid-fortified organ preservation solution with replaced buffer ameliorating
      resistance to injury during the cold static preservation with subsequent IRI.
      Numerous in vitro and in vivo experiments have shown the superiority of the HTK-N
      solution in ROS generation, microcirculation, and subsequent inflammatory
      response compared with HTK. RESULTS: According to data available to date, HTK-N
      has both lower cytotoxicity and higher protective potential than HTK. First
      clinical studies on both HTK-N for cardioplegia in cardiac surgery and for organ
      preservation for transplantation have been performed or are ongoing. CONCLUSION:
      In this review, the novelty and composition of HTK-N and studies investigating
      the potential of this new solution are focussed, after summarizing the most
      relevant molecular mechanisms of IRI.

PMID- 29637859
TI  - Melatonin Treatment Enhances Abeta Lymphatic Clearance in a Transgenic Mouse
      Model of Amyloidosis.
AB  - BACKGROUND: It has been postulated that inadequate clearance of the amyloid beta
      protein (Abeta) plays an important role in the accumulation of Abeta in sporadic
      late onset Alzheimer's disease (AD). While the blood brain barrier (BBB) has
      taken the center stage in processes involving Abeta clearance, little information
      is available about the role of the lymphatic system. We previously reported that
      Abeta is cleared through the lymphatic system. We now assessed lymphatic Abeta
      clearance by treating a mouse model of AD amyloidosis with melatonin, an Abeta
      aggregation inhibitor and immuno-regulatory neurohormone. OBJECTIVE: To confirm
      and expand our initial finding that Abeta is cleared through the lymphatic
      system. Lymphatic clearance of metabolic and cellular "waste" products from the
      brain into the peripheral lymphatic system has been known for a long time.
      However, except for our prior report, there is no additional experimental data
      published about Abeta being cleared into peripheral lymph nodes. METHODS: For
      these experiments, we used a transgenic mouse model (Tg2576) that over-expresses
      a mutant form of the Abeta precursor protein (APP) in the brain. We examined
      levels of Abeta in plasma and in lymph nodes of transgenic mice as surrogate
      markers of vascular and lymphatic clearance, respectively. Abeta levels were also
      measured in the brain and in multiple tissues. RESULTS: Clearance of Abeta
      peptides through the lymphatic system was confirmed in this study. Treatment with
      melatonin led to the following changes: 1-A statistically significant increase in
      soluble monomeric Abeta40 and an increasing trend in Abeta42 in cervical and
      axillary lymph nodes of treated mice. 2- Statistically significant decreases in
      oligomeric Abeta40 and a decreasing trend Abeta42 in the brain. CONCLUSION: The
      data expands on our prior report that the lymphatic system participates in Abeta
      clearance from the brain. We propose that abnormalities in Abeta clearance
      through the lymphatic system may contribute to the development of cerebral
      amyloidosis. Melatonin and related indole molecules (i.e., indole- 3-propionic
      acid) are known to inhibit Abeta aggregation although they do not reverse
      aggregated Abeta or amyloid fibrils. Therefore, these substances should be
      further explored in prevention trials for delaying the onset of cognitive
      impairment in high risk populations.

PMID- 29637855
TI  - Cytochrome P450s and Alcoholic Liver Disease.
AB  - Alcohol consumption causes liver diseases, designated as Alcoholic Liver Disease
      (ALD). Because alcohol is detoxified by alcohol dehydrogenase (ADH), a major
      ethanol metabolism system, the development of ALD was initially believed to be
      due to malnutrition caused by alcohol metabolism in liver. The discovery of the
      microsomal ethanol oxidizing system (MEOS) changed this dogma. Cytochrome P450
      enzymes (CYP) constitute the major components of MEOS. Cytochrome P450 2E1
      (CYP2E1) in MEOS is one of the major ROS generators in liver and is considered to
      be contributive to ALD. Our labs have been studying the relationship between
      CYP2E1 and ALD for many years. Recently, we found that human CYP2A6 and its mouse
      analog CYP2A5 are also induced by alcohol. In mice, the alcohol induction of
      CYP2A5 is CYP2E1-dependent. Unlike CYP2E1, CYP2A5 protects against the
      development of ALD. The relationship of CYP2E1, CYP2A5, and ALD is a major focus
      of this review.

PMID- 29637860
TI  - Current Methods Applied to Biomaterials - Characterization Approaches, Safety
      Assessment and Biological International Standards.
AB  - Safety and biocompatibility assessment of biomaterials are themes of constant
      concern as advanced materials enter the market as well as products manufactured
      by new techniques emerge. Within this context, this review provides an up-to-date
      approach on current methods for the characterization and safety assessment of
      biomaterials and biomedical devices from a physical-chemical to a biological
      perspective, including a description of the alternative methods in accordance
      with current and established international standards.

PMID- 29637861
TI  - Epithelial Organotypic Cultures: A Viable Model to Address Mechanisms of
      Carcinogenesis by Epitheliotropic Viruses.
AB  - In vitro culture of primary or established cell lines is one of the leading
      techniques in many areas of basic biological research. The use of pure or highly
      enriched cultures of specific cell types obtained from different tissues and
      genetics backgrounds has greatly contributed to our current understanding of
      normal and pathological cellular processes. Cells in culture are easily
      propagated generating an almost endless source of material for experimentation.
      Besides, they can be manipulated to achieve gene silencing, gene overexpression
      and genome editing turning possible the dissection of specific gene functions and
      signaling pathways. However, monolayer and suspension cultures of cells do not
      reproduce the cell type diversity, cell-cell contacts, cell-matrix interactions
      and differentiation pathways typical of the three-dimensional environment of
      tissues and organs from where they were originated. Therefore, different
      experimental animal models have been developed and applied to address these and
      other complex issues in vivo. However, these systems are costly and time
      consuming. Most importantly the use of animals in scientific research poses moral
      and ethical concerns facing a steadily increasing opposition from different
      sectors of the society. Therefore, there is an urgent need for the development of
      alternative in vitro experimental models that accurately reproduce the events
      observed in vivo to reduce the use of animals. Organotypic cultures combine the
      flexibility of traditional culture systems with the possibility of culturing
      different cell types in a 3D environment that reproduces both the structure and
      the physiology of the parental organ. Here we present a summarized description of
      the use of epithelial organotypic for the study of skin physiology, human
      papillomavirus biology and associated tumorigenesis.

PMID- 29637862
TI  - Immunometabolism in the Pathogenesis of Depressive Disorders - Therapeutic
      Considerations.
AB  - There exists a critical link between immunological processes and metabolic
      changes. Furthermore, it becomes more and more evident that changes in
      immunometabolic pathways are highly interconnected with psychological processes
      and the nervous system. Depressive disorders are a major contributor to the
      overall burden of disease worldwide. Despite extensive research, therapeutic
      interventions are often not satisfying. This may be due to the yet only partially
      elucidated pathobiochemistry underlying the development of depression which may
      be influenced by multiple factors including genetics, environment, lifestyle, and
      importantly by the immunological status. In this review article, the roles and
      consequences of the interferon gamma-dependent pathways of tryptophan breakdown
      and neopterin formation are discussed, as well as phenylalanine metabolism,
      trying to provide a rational link between immunology, metabolism and mental
      status. Besides underlining the complexity of the mechanism involved in the
      development of depression, the knowledge on relevant biomarkers may be useful in
      orchestrating personalized therapy regimes.

PMID- 29637863
TI  - Validation Cytotoxicity Assay for Lipophilic Substances.
AB  - It is challenging to disperse lipophilic substances in a validated cytotoxicity
      assay, especially for compounds with log Kow greater than or equal to 5 that may
      show false negative results. The purpose of this study was to explain the
      challenges in conducting a cytotoxicity validated test of lipophilic substances:
      Minthostachys setosa, Pimenta pseudocaryophyllus, and Drimysbrasiliensis
      essential oils. Additionally, we compared the equivalence of Neutral Red (NR) and
      3- (4,5-dimethylthiazol-2-yl) -5- (3- carboxymethoxyphenyl) -2- (4-sulfophenyl) 
      2H -tetrazolium, inner salt (MTS) in detecting cell viability. The Hydrophile
      Lipophile Balance (HLB) technique was used to evaluate the dispersion of
      essential oils and cytotoxicity in accordance to the guidelines of the OECD / GD
      129 validated cytotoxicity assay. We compared the equivalence of vital dyes by
      TOST equivalence test. According to the results, we demonstrated the possibility
      of using other ways to disperse the lipophilic substances. Based on the HLB
      theory, we selected polysorbate 20 as the best solubilizing agent of the
      essential oils studied in D10 culture medium.

PMID- 29637864
TI  - Future Perspectives in the Diagnosis of Neuropsychiatric Lupus by Advanced
      Magnetic Resonance Imaging Techniques.
AB  - Neuropsychiatric (NP) syndromes are an important cause of morbi-mortality in
      patients with Systemic Lupus Erythematosus (SLE). Despite remarkable recent
      progress, there are no definite methods to diagnose neuropsychiatric SLE (NPSLE)
      or to differentiate primary NPSLE from secondary causes. NPSLE remains a
      diagnosis of exclusion, and the clinical judgment is still the main approach to
      the correct diagnosis. Within this complex context, the Magnetic Resonance
      Imaging (MRI) has both a diagnostic role, by showing the nervous system
      involvement on one hand and excluding other causes on the other hand, and a
      prognostic role, help in assessing the lesions and monitoring the evolution.
      Conventional MRI shows brain involvement in around half of the patients, although
      the described findings are rather non-specific and present in many other
      diseases. However, many advanced MRI techniques are becoming increasingly used
      over the last period, showing abnormalities even in normal-appearing brains on
      conventional MRI. These MRI techniques hold promise to have a higher sensitivity
      and specificity than conventional MRI for NPSLE related changes. This review
      explores the place and the future perspectives of different advanced MRI
      techniques in NPSLE.

PMID- 29637865
TI  - Clinico-epidemiological Study of Morphea from a Tertiary Care Hospital.
AB  - INTRODUCTION: Morphea is an uncommon disease that presents with skin induration
      and sclerosis. The disease is common in Caucasians and there are few studies
      describing the clinicoepidemiological profile of these patients from the Indian
      subcontinent. METHODS: This prospective study was conducted during a three year
      period from June 2014 to May 2017. All patients of morphea presenting to the
      dermatology outpatient department were evaluated for parameters like age, sex,
      duration, age of onset, clinical subtype and possible disease associations and
      triggering factors. The data was analysed, tabulated and mean, standard deviation
      and percentages calculated. RESULTS: 47 patients were incorporated into the
      study. These comprised of 10 (21.28%) males and 37 (78.72%) females. The average
      age of the patients was 23.92 +/- 12.07 years with a mean age of onset being
      22.13 +/- 12.51 years. 22 (46.80%) patients presented within one year of onset of
      disease. Plaque morphea was the commonest type seen in 31 (65.96%) patients
      followed by linear morphea in 9 (19.15%) patients. We found preceding trauma in 3
      patients and morphea developed following herpes zoster and intramuscular
      injection in one patient each. CONCLUSION: Morphea is an uncommon disease that is
      seen predominantly in females and young individuals. Circumscribed plaque morphea
      is the commonest variant. Certain predisposing factors like trauma can precede
      it.

PMID- 29637866
TI  - Stem Cell Interventions for Bone Healing: Fractures and Osteoporosis.
AB  - With the ageing population, musculoskeletal conditions are becoming more
      inherent. Delayed union is defined as a slower than normal fracture healing
      response, with no healing after 4 to 6 months; however, the union is anticipated
      given sufficient time. In the context of delayed/non-union, fragility fractures
      in osteoporotic populations carry significant patient morbidity and socioeconomic
      costs. Multiple mechanisms hinder fracture healing in osteoporotic patients,
      imbalanced bone remodelling leads to impaired bone microarchitecture due to
      reduced osteoblast number and activity and as such, callus formation is
      diminished. Since stem cells can self-renew and differentiate into various tissue
      lineages, they are becoming very popular in tissue regeneration in
      musculoskeletal conditions. In this review, we discuss the role of stem cells in
      physiological fracture healing and their potential therapeutic use following a
      fracture. We explore the potential of stem cells, the release of chemokines and
      cytokines to reduce fracture risk in osteoporosis.

PMID- 29637867
TI  - ACP5: its structure, distribution, regulation and novel functions.
AB  - BACKGROUND: Tartrate-resistant acid phosphatase 5 (ACP5) is an evolutionarily
      conserved and multifunctional protein that is involved in generations of reactive
      oxygen species, normal bone development, osteoblast regulation and macrophage
      function, affecting a series of pathways, as well as reflecting bone resorption
      and osteoclast activity. METHODS: Literature searches, systematic reviews and
      assessments about the structure, distribution, regulation and novel functions of
      ACP5 were performed in this review from PubMed and Medline databases. RESULTS:
      Studies demonstrate that RANKL can increase the expression of ACP5 through NFATc1
      and c-Fos to accelerate osteoclastogenesis, which also can be regulated by many
      regulators. Based on aforementioned information, it is shown that ACP5, together
      with the phosphatase activity, can medicate the progression and development of
      human genetic diseases and cancer. CONCLUSION: As a novel target, ACP5 plays a
      critical role in preventing, monitoring and treating various kinds of tumors, as
      well as accelerating the development of a promising therapeutic strategy for
      human genetic diseases. However, the explicit mechanism between ACP5 and cancer
      is not so clear. It is necessary and significant for us to pay more in-depth
      attention.

PMID- 29637868
TI  - Translational research: a future strategy for managing Squamous Cell Carcinoma of
      the Head and Neck?
AB  - BACKGROUND: Squamous cell carcinoma of the head and neck (SCCHN) are neoplasms
      arising from the epithelium of the first aero-digestive tract. They are very
      heterogeneous both clinically and biologically. Classic and well acknowledged
      risk factors are alcohol and tobacco consumption and other forms of smokeless
      tobacco assumption, although lately the incidence of human papilloma virus (HPV)
      related SCCHN is rapidly increasing. HPV-related tumors are very different from
      their alcohol and tobacco-associated counterpart, as they show strong chemo and
      radio sensitivity and thus can often be treated with conservative treatment
      strategies. Moreover, peculiar biologic features characterize HPV-related tumors,
      such as wild type TP53, low expression of epidermal growth factor receptor
      (EGFR), wild type CCND1 and high expression of P16. In contrast, alcohol and
      tobacco related SCCHN show opposite features, together with higher number of
      chromosomal and genetic abnormalities, conferring them chemo and radio
      resistance. METHODS: We have performed a narrative review of the PubMed database
      with the aim to study the mutational landscape of SCCHN. RESULTS: Several lines
      of evidence support the existence of at least two genetically different types of
      SCCHN, one virus-related and the other alcohol and/or tobacco-related,
      characterized by both clinical and biological opposite features. Virus related
      SCCHN are very chemo and radiosensitive, so suitable for organ preserving
      strategy, which in the near future may be induction chemotherapy followed by
      association of chemotherapy and underpowered radiotherapy. Alcohol and tobacco
      related SCCHN are themselves strongly heterogeneous and can be divided in
      different entities on the basis of the "driver" genetic aberration, responsible
      for carcinogenesis. The most frequently mutated genes in alcohol and tobacco
      related SCCHN are TP53, NOTCH1, CCND1, CDKN2A, EGFR and PI3KCA. CONCLUSIONS:
      Virus-related SCCHN can be managed with chemo-radiotherapy. Alcohol and tobacco
      related tumors should be further characterized on the basis of their "driver
      mutations" in order to select effective targeted therapies.

PMID- 29637869
TI  - 2-Methoxy-6-Acetyl-7-Methyljuglone (MAM) Induces iNOS/NO-mediated DNA Damage
      Response through Activation of MAPKs Pathways.
AB  - : Background:There are inconsistent reports about the role of Nitric Oxide (NO)
      in cancer progression and prevention. Quinones demonstrate significant anti
      cancer activities both in vitro and in vivo. Objective: We investigated the
      effect of 2-methoxy-6-acetyl-7-methyljuglone (MAM), a natural naphthoquinone
      isolated from Polygonum cuspidatum Sieb. et Zucc, on NO generation and its role
      in DNA damage in cancer cells. METHODS: BEL-7402 and A549 cells were cultured and
      treated with MAM. The NO generation, DNA damage, and protein expression were
      determined. RESULTS: MAM induced inducible nitric oxide synthase (iNOS)/NO
      mediated DNA damage response through activation of MAPKs pathways. MAM induced
      DNA damage by activating ATM/Chk2. MAM increased iNOS expression, NO production,
      and MAPKs (JNK1/2, ERK1/2, and p38MAPK) phosphorylation in concentrationand time-
      dependent manners. Furthermore, iNOS inhibitor 1400W, iNOS siRNA, and NO
      scavenger hemoglobin (Hb) could significantly reverse MAM-induced DNA damage,
      ATM/Chk2 activation, NO production, and cell death. In addition, MAPKs inhibitors
      (SP600125, U0126, and SB203580) reversed MAM-induced cell death and ATM/Chk2
      activation. MAM-induced cell death was partially reversed by 1400W and Hb but
      enhanced by L-arginine. CONCLUSION: These results suggested that MAM induced
      iNOS/NO activation and generation mediated by MAPKs pathways, which resulted in
      DNA damage.

PMID- 29637870
TI  - Microbiological Etiology of Chronic Skin Lesions in Type 2 Diabetic Subjects
AB  - INTRODUCTION: Skin lesions represent lesions that result in loss of tissues and
      their joints and often this cutaneous process is a primary or secondary
      consequence of structural changes in the same skin surface. Typo 2 diabetic
      subjects developing chronic skin lesions in the lower limbs in the western world
      are steadily increasing. We conducted a study on the etiologic incidence of
      chronic skin lesions in type II diabetic subjects in the lower limbs compared to
      subjects with chronic skin lesions (controls). MATERIALS AND METHODS: Thirty
      subjects (group "A") with chronic skin lesions (CSL controls) (19 F-11M, mean age
      67.5 +/- 7.2) in the lower limbs were admitted to our study according to a
      randomization scheme and compared a thirty (group "B") type II diabetic patients
      (18F-12M, mean age 73.5 +/- 4.9) with chronic skin lesions (CSL). These two
      groups "A" and "B" have been studied and compared on the basis of infectious
      etiology responsible for the infectious skin process. RESULTS: In the subjects of
      the "A" group we found a positive bacteriological colony test of 9 examinations
      corresponding to the total 30.0%. In the group called "B" we obtained a colony
      test positive of 12 subjects over 30 corresponding to 40.0% of the examinations.
      For the number of bacterial species identified in the "A" group we obtained 7
      mono microbial and 2 poly microbial bacteriological tests, while in the "B" group
      we observed 3 mono microbial and 9 poly microbial tests. All bacteriological
      isolates showed "in vitro" sensitivity to satisfactory aminoglycosides with MICs
      range of 0.78-1.56mg/L Conclusions: Data from this study show a different
      etiology among diabetic subjects than non-diabetic subjects. In fact, in the "B"
      group, more poly microbial bacteriological findings are found in positive culture
      studies with subjects in group "A". This phenomenon confirms an alteration of the
      skin microbiome of diabetic subjects with modification of the "opportunistic
      role" of some species of the skin bacterial flora.

PMID- 29637871
TI  - Community Acquired Pseudomonas Aeruginosa Pneumonia in a Young Athlete Man: A
      Case Report and Literature Review.
AB  - Pseudomonas aeruginosaisa commonly known as nosocomial infection agent but rarely
      previously healthy people are infected by P. aeruginosa. Here we report Community
      Acquired Pneumonia (CAP) in a 27 year old male athlete. 15 published P.
      aeruginosa CAP case reports were reviewed. 53.3% of patients were female and
      46.67% were male. The mean age was 44 years old (SD: +/-13.54). In 8 reports it
      is mentioned that the patient was a smoker. Fatality rate was 46.6% and death
      rate was not significantly different between selected antibiotic regimen, sex and
      smoking in patient's outcome. Chest strike can be a risk factor for P. aeruginosa
      CAP in athlete people. Our reported patient treated by ciprofloxacin 500 mg per
      day and healed without any Secondary complication. Fast, timely diagnosis and
      treatment is critical in Community Acquired P. aeruginosa pneumonia outcome.

PMID- 29637872
TI  - Growth Factor Changes in Cerebrospinal Fluid of Children with Mental Retardation
      before and after Neural Precursor Cell Transplantation.
AB  - OBJECTIVE: To investigate growth factor changes in cerebrospinal fluid (CSF) of
      children with mental retardation (MR) before and after neural precursor cell
      transplantation (NPCT), in an attempt to provide experimental support for the
      clinical treatment of MR with NPCT. METHODS: The study comprised of 28 MR
      children who received twice NPCT in our hospital. CSF was collected at both times
      of NPCT to assess growth factors by ELISA. In addition, the content of
      insulinlike growth factor 1 (IGF-1) in CSF was assayed to determine possible
      correlations between IGF-1 changes and the short-term therapeutic effect of NPCT.
      RESULTS: Of all the growth factors detected in CSF, only IGF-1 was increased
      significantly after NPCT (P<0.05). Fifteen of the twenty-eight MR children
      achieved short-term therapeutic efficacy, whereby the content of IGF-1 after NPCT
      was significantly higher than that before NPCT (P<0.05). There was no difference
      in IGF-1 content before and after NPCT in the remaining 13 MR children without
      shortterm therapeutic effect (P=0.657). There was a significant difference in IGF
      change between the two groups of patients (P<0.05). CONCLUSION: IGF-1 may be one
      of the mechanisms contributing to the therapeutic effect of NPCT.

PMID- 29637873
TI  - Cultured Human Retinal Pigment Epithelial (hRPE) Sheets: A Search for Suitable
      Storage Conditions.
AB  - The advancement of human retinal pigment epithelial cell (hRPE) replacement
      therapy is partly dependent on optimization of cell culture, cell preservation,
      and storage medium. This study was undertaken to search for a suitable storage
      temperature and storage medium for hRPE. hRPE monolayer sheets were cultured
      under standard conditions at 37 degrees C and then randomized for storage at six
      temperatures (4, 16, 20, 24, 28, and 37 degrees C) for 7 days. After revealing a
      suitable storage temperature, hRPE sheets were subsequently stored with and
      without the silk protein sericin added to the storage medium. Live/dead assay,
      light microscopy, pH, and phenotypic expression of various proteins were used to
      assess cell cultures stored at different temperatures. After 7 days of storage,
      hRPE morphology was best preserved at 4 degrees C. Addition of sericin to the
      storage medium maintained the characteristic morphology of the preserved cells,
      and improved pigmentation and levels of pigmentation-related proteins in the
      cultured hRPE sheets following a 7-day storage period at 4 degrees C.

PMID- 29637874
TI  - Sociodemographic characteristics and frequency of consuming home-cooked meals and
      meals from out-of-home sources: cross-sectional analysis of a population-based
      cohort study.
AB  - OBJECTIVE: To identify sociodemographic characteristics associated with frequency
      of consuming home-cooked meals and meals from out-of-home sources. DESIGN: Cross
      sectional analysis of a population-based cohort study. Frequency of consuming
      home-cooked meals, ready meals, takeaways and meals out were derived from a
      participant questionnaire. Sociodemographic characteristics regarding sex, age,
      ethnicity, working overtime and socio-economic status (SES; measured by household
      income, educational attainment, occupational status and employment status) were
      self-reported. Sociodemographic differences in higher v. lower meal consumption
      frequency were explored using logistic regression, adjusted for other key
      sociodemographic variables. SETTING: Cambridgeshire, UK. SUBJECTS: Fenland Study
      participants (n 11 326), aged 29-64 years at baseline. RESULTS: Eating home
      cooked meals more frequently was associated with being female, older, of higher
      SES (measured by greater educational attainment and household income) and not
      working overtime. Being male was associated with a higher frequency of
      consumption for all out-of-home meal types. Consuming takeaways more frequently
      was associated with lower SES (measured by lower educational attainment and
      household income), whereas eating out more frequently was associated with higher
      SES (measured by greater educational attainment and household income) and working
      overtime. CONCLUSIONS: Sociodemographic characteristics associated with frequency
      of eating meals from different out-of-home sources varied according to meal
      source. Findings may be used to target public health policies and interventions
      for promoting healthier diets and dietary-related health towards people consuming
      home-cooked meals less frequently, such as men, those with lower educational
      attainment and household income, and overtime workers.

PMID- 29637876
TI  - An Acarological Risk Model Predicting the Density and Distribution of Host
      Seeking Ixodes scapularis Nymphs in Minnesota.
AB  - Ixodes scapularis is the vector of at least seven human pathogens in Minnesota,
      two of which are known to cause Lyme disease (Borrelia burgdorferi sensu stricto
      and Borrelia mayonii). In Minnesota, the statewide incidence of Lyme disease and
      other I. scapularis-borne diseases and the geographic extent over which cases
      have been reported have both increased substantially over the last two decades.
      These changes correspond with an expanding distribution of I. scapularis over a
      similar time frame. Because the risk of exposure to I. scapularis-borne pathogens
      is likely related to the number of ticks encountered, we developed an
      acarological risk model predicting the density of host-seeking I. scapularis
      nymphs (DON) in Minnesota. The model was informed by sampling 81 sites located in
      42 counties in Minnesota. Two main foci were predicted by the model to support
      elevated densities of host-seeking I. scapularis nymphs, which included the seven
      county Minneapolis-St. Paul metropolitan area and counties in northern Minnesota,
      including Lake of the Woods and Koochiching counties. There was substantial
      heterogeneity observed in predicted DON across the state at the county scale;
      however, counties classified as high risk for I. scapularis-borne diseases and
      counties with known established populations of I. scapularis had the highest
      proportion of the county predicted as suitable for host-seeking nymphs (>= 0.13
      nymphs/100 m2). The model provides insight into areas of potential I. scapularis
      population expansion and identifies focal areas of predicted suitable habitat
      within counties where the incidence of I. scapularis-borne diseases has been
      historically low.

PMID- 29637877
TI  - Analysis of Health-Care Charges in Murine Typhus: Need for Improved Clinical
      Recognition and Diagnostics for Acute Disease.
AB  - Murine typhus, caused by Rickettsia typhi, is an undifferentiated febrile illness
      with no available rapid and sensitive diagnostic assay for use during early
      disease. We aimed to compare the health-care charges in those diagnosed with
      murine typhus to those with influenza, a febrile illness with an available rapid
      diagnostic test. A comparison of health-care-associated charges at the University
      of Texas Medical Branch at Galveston demonstrated a median of $817 for influenza
      versus $16,760 for murine typhus (P < 0.0001). Median laboratory ($184 versus
      $3,254 [P < 0.0001]) and imaging charges ($0 versus $514 [P < 0.0001]) were also
      higher in those with murine typhus. Those receiving at least one imaging study
      during their illness were greater in the murine typhus group (91.3% versus 20.3%)
      (P < 0.0001). The median time needed to establish a confirmed or presumptive
      diagnosis was 2 days for influenza compared with 9 days for murine typhus (P <
      0.0001). The median number of health-care encounters was greater for those with
      murine typhus (2 versus 1) (P < 0.0001). Eleven patients (15.9%) with influenza
      were hospitalized as a result of their illness compared with 16 (69.6%) with
      murine typhus (P < 0.0001). The estimated mortality based on disease severity at
      presentation by Acute Physiology and Chronic Health Evaluation II scoring was
      similar in the two groups-both had a median 4% mortality risk (P = 0.0893). These
      results highlight the need for improved clinical recognition and diagnostics for
      acute rickettsioses such as murine typhus.

PMID- 29637878
TI  - Prevalence of Depressive Symptoms and Related Risk Factors among Patients with
      Tuberculosis in China: A Multistage Cross-Sectional Study.
AB  - Poor mental health among tuberculosis (TB) patients affects not only their
      compliance with treatments but also their daily lives. Few studies in China have
      evaluated depressive symptoms among TB patients. The present study aimed to
      determine the prevalence of depressive symptoms and its associated risk factors
      among Chinese TB patients. A total of 1,342 TB patients were recruited using a
      multistage sampling method and interviewed using a structured questionnaire.
      Depressive symptoms were measured using the Center for Epidemiologic Studies
      Depression Scale. Multinomial logistic regression analysis was performed to
      identify risk factors of depressive symptoms. Of the 1,342 participants included
      in this study, 48.0% had depressive symptoms. Of these, 34.8% and 13.2% had mild
      and moderate-to-severe depressive symptoms, respectively. Factors associated with
      depressive symptoms included family dysfunction, TB-related stigma, poor doctor
      patient communication, and lack of knowledge about TB. Depressive symptoms are
      common among TB patients in China. Efforts of government and stakeholders in the
      development of relevant policy documents to prevent stigma and create social
      support for TB patients are necessary. This would not only promote their mental
      health but also improve their compliance with treatments.

PMID- 29637879
TI  - Parapoxvirus Infections in the Country of Georgia: A Case Series.
AB  - Infections caused by viruses of the parapoxvirus (PPV) genus, including orf and
      pseudocowpox viruses, are frequently seen in both humans and animals in many
      regions of the world. These infections are often misdiagnosed or neglected
      because of the lack of clinician awareness, inadequate diagnostic capacity, and
      their relatively mild disease presentation, which may result in affected
      individuals not seeking medical attention. Although PPV infections should be
      routinely considered in patients with cutaneous lesions, especially in those who
      have occupational exposure to farm animals, they are often excluded from the
      differential diagnosis because they are not perceived as serious, resulting in
      underestimation of the burden of disease. Since 2014, significant enhancements to
      Georgia's epidemiologic and laboratory capacity have made PPV surveillance and
      detection possible. In this study, we present information on 27 confirmed cases
      of PPV infection reported to Georgia's national surveillance system from January
      2016 through January 2017.

PMID- 29637880
TI  - Biomarkers for the Diagnosis of Cholangiocarcinoma: A Systematic Review.
AB  - Cholangiocarcinoma (CCA), a malignant tumor of the bile duct, is a major public
      health problem in many Southeast Asian countries, particularly Thailand. The slow
      progression makes it difficult for early diagnosis and most patients are detected
      in advanced stages. This study aimed to review all relevant articles related to
      the biomarkers for the diagnosis of CCA and point out potential biomarkers. A
      thorough search was performed in PubMed and ScienceDirect for CCA biomarker
      articles. Required data were extracted. A total of 46 articles that fulfilled the
      inclusion and had none of the exclusion criteria were included in the analysis
      (17, 22, 3, 4, and 1 articles on blood, tissue, bile, both blood and tissue, and
      urine biomarkers, respectively). Carbohydrate antigen 19-9 (CA19-9) and
      carcinoembryonic antigen (CEA), either alone or in combination with other
      biomarkers, are the most commonly studied biomarkers in the serum. Their
      sensitivity and specificity ranged from 47.2% to 98.2% and 89.7% to 100%,
      respectively. However, in the tissue, gene methylations and DNA-related markers
      were the most studied CCA biomarkers. Their sensitivity and specificity ranged
      from 58% to 87% and 98% to 100%, respectively. Some articles investigated
      biomarkers both in blood and tissues, particularly CA19-9 and CEA, with
      sensitivity and specificity ranging from 33% to 100% and 50% to 97.7%,
      respectively. Although quite a number of biomarkers with a potential role in the
      early detection of CCA have been established, it is difficult to single out any
      particular marker that could be used in the routine clinical settings.

PMID- 29637882
TI  - Type I Interferon Receptor Variants in Gene Regulatory Regions are Associated
      with Susceptibility to Cerebral Malaria in Malawi.
AB  - Cerebral malaria (CM) remains an important cause of morbidity and mortality. Risk
      for developing CM partially depends on host genetic factors, including variants
      encoded in the type I interferon (IFN) receptor 1 (IFNAR1). Type I IFNs bind to
      IFNAR1 resulting in increased expression of IFN responsive genes, which modulate
      innate and adaptive immune responses. To comprehensively study IFNAR1 genetic
      variant associations in Malawians with CM or uncomplicated malaria, we used a tag
      single nucleotide polymorphism approach, based on the HapMap Yoruba in Ibadan,
      Nigeria, population database. We identified three novel (rs914142, rs12626750,
      and rs1041867) and one previously published (Chr21:34696785 [C > G]) IFNAR1
      variants to be associated with CM. Some of these variants are in gene regulatory
      regions. Chr21:34696785 (C > G) is in a region encoding histone modifications and
      transcription factor-binding sites, which suggests gene regulatory activity.
      Rs12626750 is predicted to bind embryonic lethal abnormal vision system-like RNA
      binding protein 1, a RNA-binding protein which can increase the type I IFN
      response. Furthermore, we examined these variants in an expression quantitative
      trait loci database and found that a protective variant, rs914142, is associated
      with lower expression of IFNAR1, whereas the CM-associated variant rs12626750 was
      associated with increased IFNAR1 expression, suggesting that activation of the
      type I IFN pathway may contribute to pathogenesis of CM. Future functional
      studies of IFNAR1 variants are now needed to clarify the role of this pathway in
      severe malarial diseases.

PMID- 29637883
TI  - Zika Virus Outbreak, Barbados, 2015-2016.
AB  - Barbados is a Caribbean island country of approximately 285,000 people, with a
      thriving tourism industry. In 2015, Zika spread rapidly throughout the Americas,
      and its proliferation through the Caribbean islands followed suit. Barbados
      reported its first confirmed autochthonous Zika transmission to the Pan American
      Health Organization in January 2016, a month before the global public health
      emergency was declared. After detection of suspected Zika cases on Barbados in
      2015, 926 individuals were described as suspected cases, and 147 laboratory
      confirmed cases were reported through December 2016, the end of the most recent
      epidemiological year. In this short report, we describe the epidemiological
      characteristics of 926 clinical case records that were originally suspected as
      cases of Zika, and which were subsequently sent for testing and confirmation; 147
      were found positive for Zika, using reverse transcription-polymerase chain
      reaction methods, another 276 tested negative, and the remaining 503 were either
      pending results or still in the suspected category. Women were represented at
      about twice the rate of men in case records where gender was reported (71.9%),
      and confirmed cases (78.2%), and 19 of the confirmed positive cases were children
      under the age of 10.

PMID- 29637884
TI  - Babesia microti and Malaria Infection in Africa: A Pilot Serosurvey in Kilosa
      District, Tanzania.
AB  - Babesia is a tick-borne intraerythrocytic parasite that is clinically and
      diagnostically similar to malaria parasite, conferring risk of misdiagnosis in
      areas where both parasites are endemic. Data on Babesia in humans in Africa are
      lacking, despite evidence that it is present in regional animal populations.
      Samples that were collected in November 2014 to July 2015 in Kilosa district,
      Tanzania, were evaluated for evidence of malaria and Babesia infection. Clinical
      data and laboratory samples (i.e., hemoglobin, rapid diagnostic testing [RDT] for
      malaria, peripheral blood smear, and dried blood spots) from a routine survey
      were available for analysis. Dried blood spots were tested using an
      investigational enzyme linked immunosorbent assay (ELISA) against Babesia
      microti. A total of 1,030 children aged 1 month to < 5 years were evaluated; 186
      (18.1%) were malaria RDT positive, 180 (96.8%) of whom had peripheral smears
      reviewed; 70/180 (38.9%) were smear positive for parasites. The median (inter
      quartile range) and range of B. microti ELISA signal to cutoff (S/C) ratio was
      0.10 (0.06-0.15) and 0.01-1.65, respectively; the S/C ratios were significantly
      higher in subjects >= 1 year as compared with those < 1 year old (P < 0.001).
      There was also a statistically significant association between a positive RDT for
      malaria and the Babesia S/C (median 0.09 versus 0.13 in RDT negative versus RDT
      positive, respectively; P < 0.001). The highest S/C ratios were
      disproportionately clustered in a few hamlets. The findings suggest that Babesia
      may be present in Kilosa district, Tanzania. However, serological cross
      reactivity and false positivity, notably between Babesia and Plasmodium spp.,
      cannot be definitively excluded and have implications for testing in other
      settings.

PMID- 29637885
TI  - Comparative Vector Competence of North American Culex pipiens and Culex
      quinquefasciatus for African and European Lineage 2 West Nile Viruses.
AB  - West Nile virus (WNV) is a mosquito-borne flavivirus that is phylogenetically
      separated into distinct lineages. Lineage 1 (L1) and lineage 2 (L2) encompass all
      WNV isolates associated with human and veterinary disease cases. Although L1 WNV
      is globally distributed, including North America, L2 WNV only recently emerged
      out of sub-Saharan Africa into Europe and Russia. The spread of L2 WNV throughout
      and beyond Europe depends, in part, on availability of competent vectors. The
      vector competence of mosquitoes within the Culex genus for WNV is well
      established for L1 WNV but less extensively studied for L2 WNV. Assessing the
      vector competence of North American Culex mosquitoes for L2 WNV will be critical
      for predicting the potential for L2 WNV emergence in North America. We address
      the vector competence of North American Culex pipiens and Culex quinquefasciatus
      for L2 WNV. Both mosquito species were highly competent for each of the L2 WNV
      strains assessed, but variation in infection, dissemination, and transmission was
      observed. An L2 WNV strain (NS10) isolated during the Greek outbreak in 2010
      exhibited a reduced capacity to infect Cx. pipiens compared with other L2 WNV
      strains. In addition, a South African L2 WNV strain (SA89) displayed a
      significantly shorter extrinsic incubation period in Cx. quinquefasciatus
      compared with other L2 WNV strains. These results demonstrate that North American
      Culex mosquito species are competent vectors of African and European L2 WNV and
      that emergence of L2 WNV is unlikely to be hindered by poor competence of North
      American vectors.

PMID- 29637886
TI  - Experimental Epidemiology of Antibiotic Resistance: Looking for an Appropriate
      Animal Model System.
AB  - Antibiotic resistance is recognized as one of the major challenges in public
      health. The global spread of antibiotic resistance is the consequence of a
      constant flow of information across multi-hierarchical interactions, involving
      cellular (clones), subcellular (resistance genes located in plasmids,
      transposons, and integrons), and supracellular (clonal complexes, genetic
      exchange communities, and microbiotic ensembles) levels. In order to study such
      multilevel complexity, we propose to establish an experimental epidemiology model
      for the transmission of antibiotic resistance with the cockroach Blatella
      germanica. This paper reports the results of five types of preliminary
      experiments with B. germanica populations that allow us to conclude that this
      animal is an appropriate model for experimental epidemiology: (i) the
      composition, transmission, and acquisition of gut microbiota and endosymbionts;
      (ii) the effect of different diets on gut microbiota; (iii) the effect of
      antibiotics on host fitness; (iv) the evaluation of the presence of antibiotic
      resistance genes in natural- and lab-reared populations; and (v) the preparation
      of plasmids harboring specific antibiotic resistance genes. The basic idea is to
      have populations with higher and lower antibiotic exposure, simulating the
      hospital and the community, respectively, and with a certain migration rate of
      insects between populations. In parallel, we present a computational model based
      on P-membrane computing that will mimic the experimental system of antibiotic
      resistance transmission. The proposal serves as a proof of concept for the
      development of more-complex population dynamics of antibiotic resistance
      transmission that are of interest in public health, which can help us evaluate
      procedures and design appropriate interventions in epidemiology.

PMID- 29637887
TI  - Elevated Levels of Urinary 8-oxodG Correlate with Persistent Periductal Fibrosis
      after Praziquantel Treatment in Chronic Opisthorchiasis.
AB  - Previous studies demonstrated that urinary 8-oxodG is a predictive biomarker for
      Opisthorchis viverrini (OV)-associated hepatobiliary disease (HBD) and
      cholangiocarcinoma (CCA). This study examined the effects of praziquantel
      treatment on the profile of urinary 8-oxodG in relation to HBD status. Infection
      with OV, levels of urinary 8-oxodG, and HBD status in terms of periductal
      fibrosis (PDF) assessed by abdominal ultrasonography (US) were monitored and
      compared in cohorts of participants in Khon Kaen, Thailand, before and 1 year
      after praziquantel treatment. Urinary 8-oxodG levels significantly decreased
      after treatment compared with the baseline level in OV-infected participants who
      had no HBD (PDF negative; PDF-ve) (N = 14). Levels of 8-oxodG were unchanged
      after treatment in OV-infected subjects (OV+ve) who had positive PDF (N = 52).
      Within the positive PDF (PDF+ve) group who became PDF-ve after treatment, there
      was no significant change in 8-oxodG levels between pre-and posttreatment
      (reversible PDF = 65.3%). In those who had persistent PDF+ve at both ultrasound
      sampling points, there was no significant difference in urinary 8-oxodG levels
      between pre- and posttreatment (persistent PDF = 34.6%). Based on a logistic
      regression model and receiver operation curve analysis, the increase of 8-oxodG
      levels was found to be associated with increasing risk of PDF. Measurement of
      urinary 8-oxodG and US increased the likelihood of discovering persistent PDF,
      which is a predictable condition for the patients at risk of OV-associated CCA.
      To identify high-risk individuals for CCA, it is useful to perform US in
      combination with urinary 8-oxodG measurement.

PMID- 29637888
TI  - The effectiveness and cost-effectiveness of screening for active tuberculosis
      among migrants in the EU/EEA: a systematic review.
AB  - BACKGROUND: The foreign-born population make up an increasing and large
      proportion of tuberculosis (TB) cases in European Union/European Economic Area
      (EU/EEA) low-incidence countries and challenge TB elimination efforts. Methods:
      We conducted a systematic review to determine effectiveness (yield and
      performance of chest radiography (CXR) to detect active TB, treatment outcomes
      and acceptance of screening) and a second systematic review on cost-effectiveness
      of screening for active TB among migrants living in the EU/EEA. Results: We
      identified six systematic reviews, one report and three individual studies that
      addressed our aims. CXR was highly sensitive (98%) but only moderately specific
      (75%). The yield of detecting active TB with CXR screening among migrants was 350
      per 100,000 population overall but ranged widely by host country (110-2,340),
      migrant type (170-1,192), TB incidence in source country (19-336) and screening
      setting (220-1,720). The CXR yield was lower (19.6 vs 336/100,000) and the
      numbers needed to screen were higher (5,076 vs 298) among migrants from source
      countries with lower TB incidence (<= 50 compared with >= 350/100,000). Cost
      effectiveness was highest among migrants originating from high (> 120/100,000) TB
      incidence countries. The foreign-born had similar or better TB treatment outcomes
      than those born in the EU/EEA. Acceptance of CXR screening was high (85%) among
      migrants. Discussion: Screening programmes for active TB are most efficient when
      targeting migrants from higher TB incidence countries. The limited number of
      studies identified and the heterogeneous evidence highlight the need for further
      data to inform screening programmes for migrants in the EU/EEA.

PMID- 29637890
TI  - West Nile virus outbreak in humans and epidemiological surveillance, west
      Andalusia, Spain, 2016.
AB  - In Andalusia, Spain, West Nile virus (WNV) surveillance takes place from April to
      November, during the active vector period. Within this area seroconversion to
      this virus was evidenced in wild birds in 2004, affecting horses and two humans
      for the first time in 2010. Since 2010, the virus has been isolated every year in
      horses, and national and regional surveillance plans have been updated with the
      epidemiological changes found. WNV is spreading rapidly throughout southern
      Europe and has caused outbreaks in humans. Here we describe the second WNV
      outbreak in humans in Andalusia, with three confirmed cases, which occurred
      between August and September 2016, and the measures carried out to control it.
      Surveillance during the transmission season is essential to monitor and ensure
      prompt identification of any outbreaks.

PMID- 29637889
TI  - The effectiveness and cost-effectiveness of screening for latent tuberculosis
      among migrants in the EU/EEA: a systematic review.
AB  - BackgroundMigrants account for a large and growing proportion of tuberculosis
      (TB) cases in low-incidence countries in the European Union/European Economic
      Area (EU/EEA) which are primarily due to reactivation of latent TB infection
      (LTBI). Addressing LTBI among migrants will be critical to achieve TB
      elimination. Methods: We conducted a systematic review to determine effectiveness
      (performance of diagnostic tests, efficacy of treatment, uptake and completion of
      screening and treatment) and a second systematic review on cost-effectiveness of
      LTBI screening programmes for migrants living in the EU/EEA. Results: We
      identified seven systematic reviews and 16 individual studies that addressed our
      aims. Tuberculin skin tests and interferon gamma release assays had high
      sensitivity (79%) but when positive, both tests poorly predicted the development
      of active TB (incidence rate ratio: 2.07 and 2.40, respectively). Different LTBI
      treatment regimens had low to moderate efficacy but were equivalent in preventing
      active TB. Rifampicin-based regimens may be preferred because of lower
      hepatotoxicity (risk ratio = 0.15) and higher completion rates (82% vs 69%)
      compared with isoniazid. Only 14.3% of migrants eligible for screening completed
      treatment because of losses along all steps of the LTBI care cascade. Limited
      economic analyses suggest that the most cost-effective approach may be targeting
      young migrants from high TB incidence countries. Discussion: The effectiveness of
      LTBI programmes is limited by the large pool of migrants with LTBI, poorly
      predictive tests, long treatments and a weak care cascade. Targeted LTBI
      programmes that ensure high screening uptake and treatment completion will have
      greatest individual and public health benefit.

PMID- 29637892
TI  - Internet Addiction: Starting the Debate on Health and Well-Being of Children
      Overexposed to Digital Media.

PMID- 29637891
TI  - A national retrospective survey of anisakidosis in France (2010-2014): decreasing
      incidence, female predominance, and emerging allergic potential.
AB  - A retrospective survey was carried out over the years 2010-2014 among all
      Parasitology laboratories of University hospitals in France (ANOFEL network). The
      objective was to estimate the incidence of anisakidosis in France as new culinary
      habits such as the consumption of raw fish (sushi) or undercooked fish are
      increasing. A total of 37 cases of anisakidosis were notified by all French
      laboratories: 7 proven cases with evidence of a worm, 12 possible cases with
      abdominal pain after consumption of raw fish with detection of anti-Anisakis
      precipitins, and 18 allergic cases defined as acute manifestations after
      consumption of fish, associated with specific IgE for Anisakis. The median age of
      affected individuals was 42 years (11-69) and there was a significant
      predominance of women (67%). Compared with previous surveys in France, this study
      indicates a decrease in clinical cases of anisakidosis and illustrates the
      emerging allergic potential of anisakids.

PMID- 29637893
TI  - Pediatric Ambulatory and Hospital Networks for Surveillance and Clinical
      Epidemiology of Community-Acquired Infections.

PMID- 29637894
TI  - Diversity of Service Systems in Pediatric Surgery for Fetuses, Neonates, Infants,
      Children, and Adolescents in Europe.

PMID- 29637895
TI  - Jean Durlach (1925-2017).

PMID- 29637896
TI  - Effect of urine pH and magnesium on calcium oxalate saturation.
AB  - Hypomagnesiuria is a common biochemical finding in patients with calcium oxalate
      (CaOx) nephrolithiasis. Clinical trials using Mg supplements as therapy against
      CaOx stones have shown mixed results. We tested the effect of Mg administration
      in healthy subjects under conditions of controlled urine pH (UpH) on urinary Ca
      excretion rate (UCaV) and CaOx saturation. This is a 4-phase, double blind,
      placebo-controlled, metabolic crossover study performed in healthy volunteers. Mg
      lactate (MgLact2) was used as Mg supplement. High UpH and low UpH were achieved
      by administration of potassium citrate (K3Citrate) and ammonium chloride (NH4Cl),
      respectively, with potassium balance maintained by KCl. Eight participants
      completed 4 phases of study. The interventions successfully modulated 24-h UpH
      (7.0 +/- 0.4 vs. 5.7 +/- 0.6 in high vs low pH phases; P<0.001). Administration
      of MgLact2 increased UMgV [175.8 +/- 40.2 vs 93.4 +/- 39.7 mg/day (7.2 +/- 1.7 vs
      3.8 +/- 1.6 mmol/day), high vs low Mg phase; P<0.001], and increased pH both at
      low (5.6 +/- 0.5 to 5.8 +/- 0.7; P = 0.02) and high UpH (6.9 +/- 0.4 to 7.0 +/-
      0.3; P = 0.01). At a given urine pH, Mg supplementation marginally increased
      UCaV, but did not alter UOxV or CaOx saturation. Provision of an alkali load
      significantly lowered UCaV and saturation of CaOx at any level of UMgV. Compared
      to changes in UMgV, changes in UpH play a more significant role in determining
      urine CaOx saturation in healthy subjects. Mg supplements are likely to reduce
      CaOx saturation if they also raise urine pH.

PMID- 29637897
TI  - The effect of magnesium supplementation on muscle fitness: a meta-analysis and
      systematic review.
AB  - Increasing evidence supports a role of magnesium (Mg) in skeletal muscle
      function. However, no systematic review or meta-analysis has summarized data on
      Mg supplementation in relation to muscle fitness in humans. Thus, this study
      aimed to quantitatively assess the effect of Mg supplementation on muscle
      fitness. A meta-analysis and systematic review. Medline database and other
      sources were searched for randomized clinical trials through July 2017. Studies
      that reported results regarding at least one of the following outcomes: leg
      strength, knee extension strength, peak torque, muscle power, muscle work, jump,
      handgrip, bench press weights, resistant exercise, lean mass, muscle mass, muscle
      strength, walking speed, Repeated Chair Stands, and TGUG were included.
      Measurements of the association were pooled using a fixed-effects model and
      expressed as weighted mean differences (WMDs) with 95% confidence intervals (95%
      CIs). Fourteen randomized clinical trials targeting 3 different populations were
      identified: athletes or physically active individuals (215 participants; mean
      age: 24.9 years), untrained healthy individuals (95 participants; mean age: 40.2
      years), and elderly or alcoholics (232 participants; mean age: 62.7 years). The
      beneficial effects of Mg supplementation appeared to be more pronounced in the
      elderly and alcoholics, but were not apparent in athletes and physically active
      individuals. The results of the meta-analysis suggested that no significant
      improvements in the supplementation group were observed regarding isokinetic peak
      torque extension [WMD = 0.87; 95% CI = (-1.43, 3.18)], muscle strength [WMD =
      0.87; 95% CI = (-0.12, 1.86)] or muscle power [WMD = 3.28; 95% CI = (-14.94,
      21.50)]. Evidence does not support a beneficial effect of Mg supplementation on
      muscle fitness in most athletes and physically active individuals who have a
      relatively high Mg status. But Mg supplementation may benefit individuals with Mg
      deficiency, such as the elderly and alcoholics.

PMID- 29637899
TI  - Markerless motion estimation for motion-compensated clinical brain imaging.
AB  - Motion-compensated brain imaging can dramatically reduce the artifacts and
      quantitative degradation associated with voluntary and involuntary subject head
      motion during positron emission tomography (PET), single photon emission computed
      tomography (SPECT) and computed tomography (CT). However, motion-compensated
      imaging protocols are not in widespread clinical use for these modalities. A key
      reason for this seems to be the lack of a practical motion tracking technology
      that allows for smooth and reliable integration of motion-compensated imaging
      protocols in the clinical setting. We seek to address this problem by
      investigating the feasibility of a highly versatile optical motion tracking
      method for PET, SPECT and CT geometries. The method requires no attached markers,
      relying exclusively on the detection and matching of distinctive facial features.
      We studied the accuracy of this method in 16 volunteers in a mock imaging
      scenario by comparing the estimated motion with an accurate marker-based method
      used in applications such as image guided surgery. A range of techniques to
      optimize performance of the method were also studied. Our results show that the
      markerless motion tracking method is highly accurate (<2 mm discrepancy against a
      benchmarking system) on an ethnically diverse range of subjects and, moreover,
      exhibits lower jitter and estimation of motion over a greater range than some
      marker-based methods. Our optimization tests indicate that the basic pose
      estimation algorithm is very robust but generally benefits from rudimentary
      background masking. Further marginal gains in accuracy can be achieved by
      accounting for non-rigid motion of features. Efficiency gains can be achieved by
      capping the number of features used for pose estimation provided that these
      features adequately sample the range of head motion encountered in the study.
      These proof-of-principle data suggest that markerless motion tracking is amenable
      to motion-compensated brain imaging and holds good promise for a practical
      implementation in clinical PET, SPECT and CT systems.

PMID- 29637898
TI  - A 6-month follow-up of disability, quality of life, and depressive and anxiety
      symptoms in pediatric migraine with magnesium prophylaxis.
AB  - Magnesium is frequently used for pediatric migraine prophylaxis. The aim of this
      study was to evaluate to which extent the disability levels, quality of life
      (QOL), and anxiety and depressive symptoms change after 6-month magnesium
      prophylaxis in pediatric migraine. This is a follow-up study of 34 children aged
      7-17 years with migraine treated with oral magnesium. Disability due to migraine
      was assessed by the Pediatric Migraine Disability Assessment tool (PedMIDAS), QOL
      was assessed by the KIDSCREEN-27, and anxiety and depressive symptoms were
      assessed by the Revised Child Anxiety and Depression Scale (RCADS). PedMIDAS
      scores significantly decreased from baseline to end-point (F(df, dferror) = 11.10
      (1.63, 50.49), p<0.001), as well as anxiety (F(df, dferror) = 8.95 (1.64, 50.67),
      p = 0.001) and depressive symptoms (F(df, dferror) = 8.91 (1.59, 49.29), p =
      0.001). Considering the KIDSCREEN-27, scores for physical and psychological well
      being and social support domain significantly increased from baseline to end
      point (p<=0.01). After 6 months of magnesium prophylaxis, disability due to
      migraine significantly decreased, whereas physical and psychosocial well-being
      improved. Children also reported fewer anxiety and depressive symptoms. More
      follow-up and randomized controlled clinical trials are needed to propose
      clinical recommendations for magnesium prophylaxis in pediatric migraine.

PMID- 29637900
TI  - Tunable magnetic coupling in Mn-doped monolayer MoS2 under lattice strain.
AB  - First-principles calculations are conducted to study the electronic and magnetic
      states of Mn-doped monolayer MoS2 under lattice strain. Mn-doped MoS2 exhibits
      half-metallic and ferromagnetic (FM) characteristics in which the majority spin
      channel exhibits metallic features but there is a bandgap in the minority spin
      channel. The FM state and the total magnetic moment of 1 u B are always
      maintained for the larger supercells of monolayer MoS2 with only one doped Mn, no
      matter under tensile or compressive strain. Furthermore, the FM state will be
      enhanced by the tensile strain if two Mo atoms are substituted by Mn atoms in the
      monolayer MoS2. The magnetic moment increases up to 0.50 u B per unit cell at a
      tensile strain of 7%. However, the Mn-doped MoS2 changes to metallic and
      antiferromagnetic under compressive strain. The spin polarization of Mn 3d
      orbitals disappears gradually with increasing compressive strain, and the
      superexchange interaction between Mn atoms increases gradually. The results
      suggest that the electronic and magnetic properties of Mn-doped monolayer MoS2
      can be effectively modulated by strain engineering providing insight into
      application to electronic and spintronic devices.

PMID- 29637901
TI  - Research and development of 3D printed vasculature constructs.
AB  - Artificial blood vessels must be strong, flexible, and must not lead to blockage
      after implantation. It is therefore important to select an appropriate
      fabrication process for products to meet these requirements. This review
      discusses the current methods for making artificial blood vessels, focusing on
      fabrication principle, materials, and applications. Among these methods, 3D
      printing is very promising since it has the unique capability to make complicated
      three-dimensional structures with multiple types of materials, and can be
      completely digitalized. Therefore, new developments in 3D printing of artificial
      blood vessels are also summarized here. This review provides a reference for the
      fusion of multiple processes and further improvement of artificial blood vessel
      fabrication.

PMID- 29637902
TI  - Protecting interventional radiology and cardiology staff: Are current designs of
      lead glasses and eye dosemeters fit for purpose?

PMID- 29637903
TI  - Dosimetric characteristics of the University of Washington Clinical Neutron
      Therapy System.
AB  - The University of Washington (UW) Clinical Neutron Therapy System (CNTS), which
      generates high linear energy transfer fast neutrons through interactions of 50.5
      MeV protons incident on a Be target, has depth-dose characteristics similar to 6
      MV x-rays. In contrast to the fixed beam angles and primitive blocking used in
      early clinical trials of neutron therapy, the CNTS has a gantry with a full 360
      degrees  of rotation, internal wedges, and a multi-leaf collimator (MLC). Since
      October of 1984, over 3178 patients have received conformal neutron therapy
      treatments using the UW CNTS. In this work, the physical and dosimetric
      characteristics of the CNTS are documented through comparisons of measurements
      and Monte Carlo simulations. A high resolution computed tomography scan of the
      model 17 ionization chamber (IC-17) has also been used to improve the accuracy of
      simulations of the absolute calibration geometry. The response of the IC-17
      approximates well the kinetic energy released per unit mass (KERMA) in water for
      neutrons and photons for energies from a few tens of keV up to about 20 MeV.
      Above 20 MeV, the simulated model 17 ion chamber response is 20%-30% higher than
      the neutron KERMA in water. For CNTS neutrons, simulated on- and off-axis output
      factors in water match measured values within ~2%  +/-  2% for rectangular and
      irregularly shaped field with equivalent square areas ranging in a side dimension
      from 2.8 cm to 30.7 cm. Wedge factors vary by less than 1.9% of the measured dose
      in water for clinically relevant field sizes. Simulated tissue maximum ratios in
      water match measured values within 3.3% at depths up to 20 cm. Although the
      absorbed dose for water and adipose tissue are within 2% at a depth of 1.7 cm,
      the absorbed dose in muscle and bone can be as much as 12 to 40% lower than the
      absorbed dose in water. The reported studies are significant from a historical
      perspective and as additional validation of a new tool for patient quality
      assurance and as an aid in ongoing efforts to clinically implement advanced
      treatment techniques, such as intensity modulated neutron therapy, at the UW.

PMID- 29637904
TI  - Comparison of normal tissue dose calculation methods for epidemiological studies
      of radiotherapy patients.
AB  - Radiation dosimetry is an essential input for epidemiological studies of
      radiotherapy patients aimed at quantifying the dose-response relationship of late
      term morbidity and mortality. Individualised organ dose must be estimated for all
      tissues of interest located in-field, near-field, or out-of-field. Whereas
      conventional measurement approaches are limited to points in water or
      anthropomorphic phantoms, computational approaches using patient images or human
      phantoms offer greater flexibility and can provide more detailed three
      dimensional dose information. In the current study, we systematically compared
      four different dose calculation algorithms so that dosimetrists and
      epidemiologists can better understand the advantages and limitations of the
      various approaches at their disposal. The four dose calculations algorithms
      considered were as follows: the (1) Analytical Anisotropic Algorithm (AAA) and
      (2) Acuros XB algorithm (Acuros XB), as implemented in the Eclipse treatment
      planning system (TPS); (3) a Monte Carlo radiation transport code, EGSnrc; and
      (4) an accelerated Monte Carlo code, the x-ray Voxel Monte Carlo (XVMC). The four
      algorithms were compared in terms of their accuracy and appropriateness in the
      context of dose reconstruction for epidemiological investigations. Accuracy in
      peripheral dose was evaluated first by benchmarking the calculated dose profiles
      against measurements in a homogeneous water phantom. Additional simulations in a
      heterogeneous cylinder phantom evaluated the performance of the algorithms in the
      presence of tissue heterogeneity. In general, we found that the algorithms
      contained within the commercial TPS (AAA and Acuros XB) were fast and accurate in
      field or near-field, but not acceptable out-of-field. Therefore, the TPS is best
      suited for epidemiological studies involving large cohorts and where the organs
      of interest are located in-field or partially in-field. The EGSnrc and XVMC codes
      showed excellent agreement with measurements both in-field and out-of-field. The
      EGSnrc code was the most accurate dosimetry approach, but was too slow to be used
      for large-scale epidemiological cohorts. The XVMC code showed similar accuracy to
      EGSnrc, but was significantly faster, and thus epidemiological applications seem
      feasible, especially when the organs of interest reside far away from the field
      edge.

PMID- 29637905
TI  - Realistic modeling of deep brain stimulation implants for electromagnetic MRI
      safety studies.
AB  - We propose a framework for electromagnetic (EM) simulation of deep brain
      stimulation (DBS) patients in radiofrequency (RF) coils. We generated a model of
      a DBS patient using post-operative head and neck computed tomography (CT) images
      stitched together into a 'virtual CT' image covering the entire length of the
      implant. The body was modeled as homogeneous. The implant path extracted from the
      CT data contained self-intersections, which we corrected automatically using an
      optimization procedure. Using the CT-derived DBS path, we built a model of the
      implant including electrodes, helicoidal internal conductor wires, loops,
      extension cables, and the implanted pulse generator. We also built four
      simplified models with straight wires, no extension cables and no loops to assess
      the impact of these simplifications on safety predictions. We simulated EM fields
      induced by the RF birdcage body coil in the body model, including at the DBS lead
      tip at both 1.5 Tesla (64 MHz) and 3 Tesla (123 MHz). We also assessed the
      robustness of our simulation results by systematically varying the EM properties
      of the body model and the position and length of the DBS implant (sensitivity
      analysis). The topology correction algorithm corrected all self-intersection and
      curvature violations of the initial path while introducing minimal deformations
      (open-source code available at http://ptx.martinos.org/index.php/Main_Page). The
      unaveraged lead-tip peak SAR predicted by the five DBS models (0.1 mm resolution
      grid) ranged from 12.8 kW kg-1 (full model, helicoidal conductors) to 43.6 kW kg
      1 (no loops, straight conductors) at 1.5 T (3.4-fold variation) and 18.6 kW kg-1
      (full model, straight conductors) to 73.8 kW kg-1 (no loops, straight conductors)
      at 3 T (4.0-fold variation). At 1.5 T and 3 T, the variability of lead-tip peak
      SAR with respect to the conductivity ranged between 18% and 30%. Variability with
      respect to the position and length of the DBS implant ranged between 9.5% and
      27.6%.

PMID- 29637907
TI  - Pressure gradients fail to predict diffusio-osmosis.
AB  - We present numerical simulations of diffusio-osmotic flow, i.e. the fluid flow
      generated by a concentration gradient along a solid-fluid interface. In our
      study, we compare a number of distinct approaches that have been proposed for
      computing such flows and compare them with a reference calculation based on
      direct, non-equilibrium molecular dynamics simulations. As alternatives, we
      consider schemes that compute diffusio-osmotic flow from the gradient of the
      chemical potentials of the constituent species and from the gradient of the
      component of the pressure tensor parallel to the interface. We find that the
      approach based on treating chemical potential gradients as external forces acting
      on various species agrees with the direct simulations, thereby supporting the
      approach of Marbach et al (2017 J. Chem. Phys. 146 194701). In contrast, an
      approach based on computing the gradients of the microscopic pressure tensor does
      not reproduce the direct non-equilibrium results.

PMID- 29637906
TI  - Lesion detectability in 2D-mammography and digital breast tomosynthesis using
      different targets and observers.
AB  - This work investigates the detection performance of specialist and non-specialist
      observers for different targets in 2D-mammography and digital breast
      tomosynthesis (DBT) using the OPTIMAM virtual clinical trials (VCT) Toolbox and a
      4-alternative forced choice (4AFC) assessment paradigm. Using 2D-mammography and
      DBT images of virtual breast phantoms, we compare the detection limits of simple
      uniform spherical targets and irregular solid masses. Target diameters of 4 mm
      and 6 mm have been chosen to represent target sizes close to the minimum
      detectable size found in breast screening, across a range of controlled contrast
      levels. The images were viewed by a set of specialist observers (five medical
      physicists and six experienced clinical readers) and five non-specialists.
      Combined results from both observer groups indicate that DBT has a significantly
      lower detectable threshold contrast than 2D-mammography for small masses (4 mm:
      2.1% [DBT] versus 6.9% [2D]; 6 mm: 0.7% [DBT] versus 3.9% [2D]) and spheres (4
      mm: 2.9% [DBT] versus 5.3% [2D]; 6 mm: 0.3% [DBT] versus 2.2% [2D]) (p  < 
      0.0001). Both observer groups found spheres significantly easier to detect than
      irregular solid masses for both sizes and modalities (p  <  0.0001) (except 4 mm
      DBT). The detection performances of specialist and non-specialist observers were
      generally found to be comparable, where each group marginally outperformed the
      other in particular detection tasks. Within the specialist group, the clinical
      readers performed better than the medical physicists with irregular masses (p  < 
      0.0001). The results indicate that using spherical targets in such studies may
      produce over-optimistic detection thresholds compared to more complex masses, and
      that the superiority of DBT for detecting masses over 2D-mammography has been
      quantified. The results also suggest specialist observers may be supplemented by
      non-specialist observers (with training) in some types of 4AFC studies.

PMID- 29637908
TI  - Topical timolol in PHACES syndrome: Is it safe?

PMID- 29637909
TI  - Incidence of leprosy in Firozabad district (Uttar Pradesh).
AB  - Objective: To assess incidence of leprosy in Firozabad District (U.P.). Materials
      and Methods: A random sample of 148,061 population was covered by this second
      survey, spread over 259 units (230 rural/29 urban). The survey was conducted
      between March 2011 and November 2012. Clinically confirmed cases detected in
      known disease-free population were labeled as incident cases and treated.
      Results: The overall incidence rate of leprosy was found to be 3.4 per 10,000
      person years; In healthy contacts it was 3.1, in paucibacillary contacts 29.7
      while it was 89.3 in multibacillary contacts. The differences in incidence rate
      of these three groups were significant (P < 0.001). Incidence rate was
      significantly higher by age; 1.1 in persons <15 years to 8.0 in those >44 years
      of age, and in high endemicity areas with three or more cases. In terms of
      incidence rate ratio (95% confidence interval), the incidence for ages 15-24
      years was 3.2 times significantly higher than for those under 15 years, 5.3 times
      (4.3-6.5) in ages 30-44 years and 7.0 times (5.6-8.7) for age >=45 years.
      Incidence rate ratio was also significantly higher in paucibacillary contacts, by
      9.5 times (7.0-13.0) and 27.7 times (18.8-40.6) in multibacillary contacts, as
      compared to healthy controls. Incidence rate ratio (95% confidence interval) was
      significantly higher by 2.9 times (2.4-3.5) in areas with endemicity status of 3
      to 5 cases and by 2.0 times (1.6-2.5) in areas with >5 cases as compared to areas
      with no endemicity. It was 2.4 times more (1.6-3.5) in Narkhi, 2.4 times higher
      (1.7-3.5) in Tundla and 3.0 times higher (2.1-4.5) in Aravon blocks than in Aeka
      block of the district. Incidence rate was also found to be significantly higher
      (3.7) among females, 1.3 times higher (1.1-1.5) than in males (2.9). Incidence
      rate ratio (95% confidence interval) was also 2.5 times higher (1.2-5.1) among
      persons having reported disease of greater than 4 years in comparison to 1.5 in
      persons having disease for 2 to 3 years. Limitations of Study: None to the best
      of our knowledge. Conclusion: The present study suggests that incidence rate of
      leprosy is significantly higher among persons of above 15 years, in females,
      among contacts of paucibacillary/multibacillary disease, in areas where >3
      leprosy cases were found and in Tundla, Narkhi and Aravon blocks in Firozabad
      district.

PMID- 29637910
TI  - Paradigm shift in antinuclear antibody negative lupus: Current evidence.

PMID- 29637912
TI  - Bowel preparation: The elderly, the hospitalized, and the colonoscope.

PMID- 29637911
TI  - Management of distal malignant biliary obstruction.

PMID- 29637913
TI  - Thiazolidinediones and risk of colorectal cancer in patients with diabetes
      mellitus: A meta-analysis.
AB  - Background/Aims: A growing body of evidence has suggested that thiazolidinediones
      (TZDs) potentially reduce the risk of colorectal cancer (CRC). This study aimed
      to evaluate the effect of TZDs on CRC risk in patients with diabetes mellitus
      (DM). Patients and Methods: A systematic search of electronic databases was
      performed for studies evaluating the exposure to TZDs and reporting CRC risk in
      diabetic patients. Pooled estimates with 95% confidence intervals (CIs) were
      estimated using fixed or random effects models. Results: A total of 10
      observational studies reporting more than 18,972 CRC cases in 2,470,768 DM
      patients were included. Meta-analysis showed a 9% reduction in CRC risk
      associated with TZDs use in all studies [relative risk (RR) =0.91, 95% CI = 0.84
      0.99, P = 0.03] and cohort studies (RR = 0.89, 95% CI = 0.80-0.99, P = 0.04),
      respectively. However, such effect was not shown in case-control studies. In
      subgroup analyses, lower CRC risk was found in Asian population (RR = 0.40, 95%
      CI = 0.29-0.53, P = 0.00), and a trend toward lower CRC risk was observed in US
      population (RR = 0.94, 95% CI = 0.88-1.01, P = 0.08). CRC risk was significantly
      modified with non-pioglitazone TZD use (RR = 0.88, 95% CI = 0.82-0.95, P = 0.00),
      but not with pioglitazone use (RR = 0.95, 95% CI = 0.89-1.01, P = 0.11). No
      significant difference was observed with cancer site (colon or rectum). There was
      considerable inherent heterogeneity across studies, partly explained by study
      location. Conclusions: This meta-analysis supports a protective association
      between TZDs use and CRC risk in patients with DM. Future well-designed
      prospective studies with larger cohorts would be needed to understand this
      association better.

PMID- 29637914
TI  - Differences in efficacy of uncovered self-expandable metal stent in relation to
      placement in the management of malignant distal biliary obstruction.
AB  - Background/Aims: Metal stent insertion is a common palliative treatment for
      distal malignant biliary obstruction (MBO) but whether placement across the
      sphincter of Oddi (SO) causes more complications or shorter survival is in
      question. The aim of this study was to compare the clinical outcomes of
      percutaneous uncovered self-expandable metal stent placement above and across the
      SO in patients with distal MBO. Patients and Methods: We retrospectively studied
      59 patients who underwent uncovered metal stent placement for distal MBO between
      January 2012 and March 2016. Stents were placed above the SO for 22 subjects
      (group A) and across the SO for 37 subjects (group B). Early cholangitis, stent
      occlusion, and overall survival time were compared between the two groups.
      Results: Clinical success was 90.9 and 86.5% for groups A and B, respectively.
      Early cholangitis occurred in 2 patients (9.1%) in group A and in 6 patients
      (16.2%) in group B (P = 0.645). Median stent patency and median survival time was
      105 and 140 days for group A, 120 and 160 days for group B, respectively. The
      stent occlusion (31.8% in group A and 21.6% in group B, P = 0.454) and the
      cumulative stent patency times (P = 0.886) did not differ between the two groups.
      There was no significant difference in cumulative patient survival between the
      two groups (P = 0.810). Conclusion: Uncovered metal stent placement across the SO
      did not significantly affect early cholangitis, stent patency, or patient
      survival.

PMID- 29637915
TI  - The incidence of and risk factors for inadequate bowel preparation in elderly
      patients: A prospective observational study.
AB  - Background/Aim: : We conducted a prospective observational study to identify the
      incidence of and risk factors for inadequate bowel preparation in elderly Chinese
      patients. Patients and Methods: We enrolled 240 outpatients over 60 years of age
      scheduled for elective colonoscopy at our university hospital between November
      2016 and April 2017. We recorded patient demographics, bowel preparation data,
      and clinical characteristics. Factors associated with inadequate bowel
      preparation were identified by multivariate logistical regression analysis.
      Results: The rate of inadequate bowel preparation was 34.6%. Factors associated
      with inadequate bowel preparation were a history of abdominal surgery (OR, 2.617;
      CI, 1.324-5.174; P = 0.006), chronic constipation (OR, 3.307; CI, 1.551-7.054; P
      = 0.002), non-compliance with dietary instructions (OR, 2.239; CI, 1.122-4.471; P
      = 0.022), non-compliance with polyethylene glycol (PEG) dosage (OR, 4.576; CI,
      1.855-11.287; P = 0.001), walking <30 minutes during preparation (OR, 2.474; CI,
      1.261-4.855; P = 0.008), interval between PEG ingestion and the onset of bowel
      activity (OR, 1.025; CI, 1.010-1.040; P = 0.001), and a last stool that was not
      clear and watery (OR, 4.191; CI, 1.529-11.485; P = 0.005). Conclusion: The
      incidence of adequate bowel preparation in elderly patients is not optimal.
      Walking <30 minutes during the PEG ingestion period may be a surrogate for bowel
      preparation failure. Future studies should identify elderly patients at risk for
      poor bowel preparation and develop interventions to improve outcomes in this
      population.

PMID- 29637916
TI  - Bowel preparation quality between hospitalized patients and outpatient
      colonoscopies.
AB  - Background/Aims: Optimal bowel preparation is essential for a complete high
      quality colonoscopy. We sought to determine whether an inpatient, as opposed to
      an ambulatory setting, would affect the quality of bowel preparation. Patients
      and Methods: A retrospective chart review was conducted in a tertiary care
      university hospital. We collected demographic data from consecutive patients who
      underwent a colonoscopy for any reason between August 2007 and April 2012.
      Results: A total of 2999 patients were included in the study with a mean age of
      50.36 (95%CI; 49.79-50.94). Males comprised 58.12%. Ambulatory patients had a
      higher rate of good bowel preparations (67.23% vs. 56.64%, P value < 0.01), a
      lower rate of poor bowel preparations (18.22% vs. 27.14%, P value < 0.01), and a
      higher rate of colonoscopy completion (86.79% vs. 77.59%, P value < 0.01). There
      was no difference between the rates of polyps detected (18.90% vs. 20.83%, P
      value = 0.22). The univariabe modeling factors associated with a sub-optimal
      bowel preparation were age OR 1.02 (95% CI, 1.01 to 1.02), chronic kidney disease
      OR 2.34 (95% CI, 1.12 to 4.88), diabetes mellitus OR 2.00 (95% CI, 1.50 to 2.68),
      hypertension OR 1.48 (95% CI, 1.11 to 1.97), anemia OR 1.81 (95% CI, 1.33 to
      2.47), and weight loss OR 1.41 (95% CI, 1.01 to 1.96). Better bowel preparation
      was associated with colonoscopies performed in the outpatient setting OR 0.63
      (95% CI, 0.54 to 0.73). Conclusion: Bowel preparation quality is affected by the
      setting in which it is performed. This result suggests that, when appropriate,
      colonoscopies should be performed on an outpatient basis. Further studies are
      required to replicate this finding.

PMID- 29637917
TI  - Effects of taste stimulation on gastric myoelectrical activity and autonomic
      balance.
AB  - Background/Aim: Sham feeding, reproducing the cephalic phase of digestion, and
      involving combined visual, olfactory, and taste stimulation affects
      gastrointestinal motility and secretory functions of the digestive system, as
      well as the sympathetic/parasympathetic balance (SPB). In this study, we aimed to
      check if taste stimulation with a single flavor affects the gastric myoelectrical
      activity (GMA) and/or SPB. Materials and Methods: Eighteen healthy volunteers
      underwent, on four separate days, 30-min electrogastrographic and
      electrocardiographic recordings: basal, with stimulation - while keeping in the
      mouth an agar cube with taste-delivering substance, and postexposure.
      Concentrations of saccharose, NaCl, citric acid, and quinine hydrochloride within
      the cubes were adjusted to 100-fold the individual taste recognition thresholds.
      SPB was determined from the heart rate variability (HRV) analysis of the recorded
      electrocardiograms. Results: A moderate but statistically significant increase in
      tachygastria and bradygastria percentage time share was observed, regardless of
      the type of taste applied. Bitter taste elicited a considerable decrease in the
      normogastria time share (from 82.8 +/- 2.5% to 73.5 +/- 3.5%, P = 0.00076) and a
      diminution of the dominant frequency (from 3.07 +/- 0.08 to 2.90 +/- 0.10 cycles
      per minute (cpm) postexposure, P = 0.01). Sour taste brought about a drop of the
      dominant power (from 42.5 +/- 1.1 to 40.1 +/- 1.4 dB, P = 0.0015). Two tastes
      hindered propagation of the gastric slow waves - the average percentage of slow
      wave coupling decreased from 77.9 +/- 3.1% to 69.5 +/- 3.1% (P = 0.0078) and from
      74.6 +/- 2.5% to 68.2 +/- 2.8% (P = 0.0054) with the bitter and the salty taste,
      respectively. Stimulation with sweet, salty, or sour taste evoked a significant
      decrease in the high frequency component of the HRV, whereas bitter taste did not
      affect the SPB. Conclusions: Oral stimulation with tastes subjectively perceived
      as unpleasant brings about disturbances of the interdigestive GMA. This, however,
      does not coincide with its effect upon SPB.

PMID- 29637918
TI  - Vitamin D supplementation in adolescents with irritable bowel syndrome: Is it
      useful? A randomized controlled trial.
AB  - Background/Aim: Vitamin D deficiency is common in irritable bowel syndrome (IBS).
      There is growing interest in the role of vitamin D in pediatric IBS. We aimed to
      evaluate the effect of vitamin D supplementation in adolescents with IBS and
      vitamin D deficiency. Patients and Methods: One hundred and twelve adolescents
      with IBS and vitamin D deficiency were randomly divided into two groups of
      matched age and sex. The first group received oral vitamin D3 2000IU/day for 6
      months and the second group received placebo for 6 months. Vitamin D status as
      well as different IBS score systems (IBS-SSS, IBS-QoL, and total score) were
      evaluated before and 6 months after treatment. Results: IBS patients who received
      vitamin D supplementation for 6 months showed significant improvement in IBS-SSS
      (P < 0.001), IBS-QoL (P < 0.001), and total score (P = 0.02) compared to IBS
      placebo group. IBS patients treated with vitamin D showed two folds increase in
      their serum vitamin D levels (from 17.2 +/- 1.3 to 39 +/- 3.3) ng/ml with P <
      0.001. While in the placebo group, their serum vitamin D levels were not
      significantly changed (P = 0.66). Vitamin D was tolerated well without any
      recorded adverse effects during the study period. Conclusion: Vitamin D
      supplementation can be effective in treating adolescents with IBS and vitamin D
      deficiency.

PMID- 29637919
TI  - Comparison of efficacy and safety between endoscopic submucosal dissection and
      transanal endoscopic microsurgery for the treatment of rectal tumor.
AB  - Background/Aim: To compare the treatment efficacy and safety between endoscopic
      submucosal dissection (ESD) and transanal endoscopic microsurgery (TEM) for the
      treatment of rectal epithelial tumors, including large adenoma, cancer, and
      subepithelial tumors (SET). Patients and Methods: We conducted a retrospective
      analysis of the medical records of 71 patients with rectal tumors who were
      treated with ESD (48 patients) or TEM (23 patients) from January 2013 to December
      2015. The patient group comprised 56 patients with epithelial tumors and 15
      patients with SET. Treatment efficacy such as en bloc resection, procedure time,
      local recurrence, hospital stay, additional procedure rate, and safety between
      the treatment groups were evaluated and analyzed. Results: There were no
      significant differences in tumor size, location, macroscopic appearance, and
      histological depth between ESD and TEM groups. For ESD compared to TEM in rectal
      epithelial tumors, en bloc resection rates were 95% vs. 93.7% and R0 resection
      rates were 92.5% vs. 87.5% (P = 0.617); in rectal SET, en bloc resection rates
      were 100% vs. 100% and R0 resection rates were 87% vs. 85% (P = 0.91). The
      procedure time was 71.5 +/- 51.3 min vs. 105.6 +/- 28.2 min (P = 0.016) for
      epithelial tumors and 32.13 +/- 13.4 min vs. 80.71 +/- 18.35 min (P = 0.00) for
      SET, respectively. Hospital stay was 4.3 +/- 1.2 days vs. 5.8 +/- 1.8 days (P =
      0.001) for epithelial tumors and 4.1 +/- 4.1 days vs. 5.5 +/- 2 days (P = 0.42)
      for rectal SET, respectively. There were no significant differences between
      recurrence rates, additional procedure rates, and complications in the two
      groups. Conclusions: ESD and TEM are both effective and safe for the treatment of
      rectal epithelial tumors and SET because of favorable R0 resection rates and
      recurrence rates. However, the ESD group showed shorter procedure times and
      hospital stays than the TEM group. Therefore, ESD should be considered more
      preferentially than TEM in the treatment of large rectal epithelial tumors and
      SET.

PMID- 29637920
TI  - New endoscopic classification of esophageal mucosa in achalasia: A predictor for
      submucosal fibrosis.
AB  - Background/Aim: In this study, we aim to investigate the predicting ability of
      one new endoscopic classification of esophageal mucosa in achalasia (EMIA) for
      submucosal fibrosis (SMF) affecting the success of peroral endoscopic myotomy
      (POEM). Patients and Methods: The endoscopic and clinical data of achalasia
      patients undergoing POEM from 2012 to 2016 were investigated retrospectively.
      According to the endoscopic images or videos, EMIA and SMF grades were recorded.
      The relation between EMIA and SMF gradings was assessed by Spearman's rank
      correlation, and the predictive factors of SMF were identified by logistic
      regression analysis. Results: A total of 568 achalasia patients who underwent
      POEM were enrolled. For EMIA classification, there were 40 (7.0%), 373 (65.7%),
      139 (24.5%), 14 (2.5%), 1 (0.2%), and 1 (0.2%) case (s) for grades a, b, c, d,
      e1, and f4, respectively. POEM procedures were aborted in 16 patients, and 93.8%
      (15/16) were due to severe SMF. Because grades e and f were rare and the related
      SMF was obvious, these two grading cases were excluded from the following
      analysis. Correlation between EMIA and SMF gradings was significant (Spearman r =
      0.62, P < 0.01). Multivariate logistic analysis, including age, sex, disease
      duration, Ling classification, previous treatment, and EMIA classification,
      demonstrated that the EMIA classification (grades c to d) was an independent
      predictor for advanced SMF (odds ratio = 26.547, 95% confidence interval: 15.809
      44.578, P < 0.01). Conclusions: The new endoscopic EMIA classification is an
      independent predictor of advanced SMF during POEM. The classification may be used
      for assessment of the difficulty and success of POEM.

PMID- 29637921
TI  - Immunohistochemical staining of cytokeratin 20 and cytokeratin 7 in colorectal
      carcinomas: Four different immunostaining profiles.
AB  - Background/Aim: Aberrant expression of CK20/CK7 is reported in a percentage of
      colorectal carcinomas (CRC); however, its relation to clinicopathological
      variables and survival data is still unclear. The objective of this study is to
      explore patterns of CK20/CK7 immunostaining in CRC and to analyse the diagnostic,
      prognostic, and predictive role of patterns of CK20/CK7 immunostaining. Materials
      and Methods: A total of 144 CRC cases were retrieved from the archives at the
      Department of Pathology, King Abdulaziz University, Jeddah, Saudi Arabia.
      Immunohistochemistry was performed using antibody to CK7 and CK20. Immunostaining
      was defined as low and high by using the extent of staining. The association of
      CK7 and CK20 with clinicopathological characteristics and survival. Results: CK20
      was expressed in a higher percentage of CRC and nodal metastasis than CK7. No
      difference in CK7 and CK20 immunostaining in primary and metastasis carcinomas
      was found. Four patterns of CK20/CK7 were identified; CK20+/CK7- (60.4%),
      CK20+/CK7+ (2.1%), CK20-/CK7- (35.4%), and CK20-/CK7+ (2.1%). There was no
      statistically significant correlation between CK20/CK7 immunohistochemical
      profile and clinicopathological characteristics, prognosis, and survival was
      determined. Conclusions: Our results may support the heterogeneity of CRC. CRC
      showed four different subclasses following patterns of relative CK20/CK7
      immunostaining. A considerable number of CRC expressed aberrant immune profile of
      CK20/CK7, which should be considered during diagnosing CRC in metastatic regions.
      Further studies on larger cohorts correlating different immunohistochemical
      cytokeratin profiles to molecular subtypes of CRC are recommended for better
      understanding of pathogenesis and behaviour of CRC.

PMID- 29637922
TI  - Candidemia after endoscopic retrograde cholangiopancreatography in an
      immunocompetent patient: A case report and literature review.
AB  - Candidemia is a rare adverse event of endoscopic retrograde
      cholangiopancreatography (ERCP). To date, several case reports of post-ERCP
      candidemia have been reported. Recently, we experienced a case of disseminated
      candidemia caused by Candida albicans with secondary complications of acute
      respiratory distress syndrome, acute kidney injury, and hematogenous candidal
      endophthalmitis following ERCP in a young healthy patient without well-recognized
      risk factors for candidemia. After intravenous and intravitreal antifungal
      therapy and intensive care, the candidemia resolved, and the patient was
      discharged without further sequela. The present case alerted us to consider
      candidemia as a rare but potentially fatal adverse event of ERCP, even in an
      immunocompetent host.

PMID- 29637924
TI  - [Study of the current status of Schistosoma haematobium infection in the European
      Union. An approach to the possible risk in Spain].
AB  - OBJECTIVE: In Europe, urogenital schistosomiasis was not endemic, however in 2014
      the first cases of a European autochthonous infection outbreak appeared in
      Corsica (France). In this work a search and description of cases, both import and
      native urogenital schistosomiasis, published in the European Union (EU) during
      the last 20 years was made. In addition, a qualitative risk assessment in Spain
      was carried out. METHODS: A bibliographic search of European Union published
      cases over the last 20 years (1997-2017) was performed using PubMed. Works that
      evidenced the presence of intermediate hosts Bulinus truncatus and Planorbarius
      metidjensis in our country were searched in PubMed, ResearchGate and Google
      Scholar. Finally, a risk assessment of urogenital schistosomiasis in Spain using
      the 2011 ECDC guide was made. RESULTS: 481 cases in the EU were found. 328 were
      imported and 152 autochthonous. All from the autochthonous cases were focused in
      Corsica, where people from different nationalities got sicked. The presence of
      two potential host species was documented in different locations of our
      geography. The result of the risk assessment in Spain was low risk. CONCLUSIONS:
      Although the risk assessment in Spain was low risk, several factors as the
      presence of intermediate hosts in Spain, the increase on migratory flows, and the
      role that the S. haematobium-bovis hybrid had in the outbreak of Corsica, must
      alert community and health authorities about the possibility that autochthonous
      cases in our country appear.

PMID- 29637925
TI  - [Occupational health administrative coordination a propos of a case: brake
      linings with asbestos in a company].
AB  - The current structure of the Spanish State of Autonomies is characterized by
      institutional pluralism and the autonomy of the different public administrations.
      In this context, the principle of coordination is fundamental for the cohesion of
      the system, but experience shows that its implementation is difficult. This paper
      examines the set of actions carried out by the administrations in relation to an
      occupational and public health problem raised in March 2016. The Public Health
      General Direction of Aragon's Government was informed of a possible use of brake
      linings with asbestos to manufacture axles for agricultural machinery by a
      Company from Zaragoza; the collaboration from Aragon's Institute of Occupational
      Safety and Health, the Industry Department and the Labour and Social Security
      Inspectorate were asked; the joint action of these administrations detected the
      use of several models of brake linings with a content of 2-5% of Chrysotile. The
      brake linings came from a Chinese company. The axles nated are sold in several
      Spanish Autonomous Communities. A national alert was activated by the SIRIPQ
      (System of Rapid Exchange of Information on Chemical Products) which is
      coordinated by the Ministry of Health, Social Services and Equality. Several
      measures were taken including: ceasing the work with the brake linings, the
      replacement of brake linings with asbestos, the immobilization of brake linings
      in the company by application of the REACH Reglament, etc. This case shows that
      the cooperation and co-responsibility of public administrations from different
      territorial, sectoral and competence areas allows improving the occupational
      risks prevention and the public health.

PMID- 29637923
TI  - Effects of Genetic Polymorphisms of CYP2B6 on the Pharmacokinetics of Bupropion
      and Hydroxybupropion in Healthy Chinese Subjects.
AB  - BACKGROUND Bupropion (BUP) is an antidepressant and its pharmacological activity
      is mediated by its major metabolite, hydroxybupropion (HBUP). We investigated the
      effects of genetic polymorphisms of CYP2B6 on BUP and HBUP to provide certain
      evidence on the clinical rational administration of BUP. MATERIAL AND METHODS
      Plasma BUP and HBUP concentrations were assayed using high performance liquid
      chromatography-tandem mass spectrometry (HPLC-MS/MS). RESULTS A total of 23
      healthy volunteers (eleven participants with CYP2B6*1/*1, 7 participants with
      CYP2B6*1/*6, 3 participants with CYP2B6*4/*6, and 2 participants with
      CYP2B6*1/*4) received orally administered 150 mg of BUP according to protocol.
      Blood samples were obtained up to 96 hours after administration. The whole blood
      was subject to genotyping by polymerase chain reaction and restriction fragment
      length polymorphism (PCR-RFLP). The concentration-time curve (AUC(0->96)),
      maximum plasma concentration (Cmax), and terminal half-life (t1/2) values of BUP
      in CYP2B6*1/*4 were lower than those of CYP2B6*1/*1. By contrast, the time to
      Cmax (tmax) value of the former was higher than that of the latter. The HBUP
      AUC(0->96) values in CYP2B6*4/*6 and CYP2B6*1/*4 increased to values 1.12-fold
      and 1.98-fold, compared with CYP2B6*1/*1 carriers. However, the HBUP AUC(0->96)
      value in CYP2B6*1/*1 was 1.51-fold higher than that in CYP2B6*1/*6. Similarly,
      the HBUP Cmax values in CYP2B6*4/*6 and CYP2B6*1/*4 increased by 1.12-fold and
      1.97-fold, whereas the HBUP Cmax value in CYP2B6*1/*6 decreased to a value 1.64
      fold lower than that in CYP2B6*1/*1. CONCLUSIONS Genetic polymorphisms of CYP2B6
      influence the pharmacokinetic parameters of BUP and HBUP and thus establish
      rational BUP administration for Chinese patients in clinical settings.

PMID- 29637927
TI  - Erratum: Peptides derived from Plasmodium falciparum leucine-rich repeat 1 bind
      to serine/threonine phosphatase type 1 and inhibit parasite growth in vitro
      [Corrigendum].
AB  - [This corrects the article on p. 85 in vol. 12.].

PMID- 29637926
TI  - Condensing embryology teaching: alternative perspectives.

PMID- 29637928
TI  - Cardiac surgery risk scoring systems: In quest for the best.

PMID- 29637929
TI  - Correction: Global health security: where is the data to inform health system
      strengthening?
AB  - [This corrects the article DOI: 10.1136/bmjgh-2017-000481.][This corrects the
      article DOI: 10.1136/bmjgh-2017-000481.].

PMID- 29637930
TI  - Correction: Fall-related accidents among hikers in the Austrian Alps: a 9-year
      retrospective study.
AB  - [This corrects the article DOI: 10.1136/bmjsem-2017-000304.][This corrects the
      article DOI: 10.1136/bmjsem-2017-000304.].

PMID- 29637931
TI  - Commentary: Injecting Instructions into Premotor Cortex.

PMID- 29637932
TI  - Medical students' perspectives on teaching a concise embryology course.

PMID- 29637933
TI  - Commentary: Ketone Diester Ingestion Impairs Time-Trial Performance in
      Professional Cyclists.

PMID- 29637934
TI  - Commentary: Open and Laparoscopic Colposuspension in Girls With Refractory
      Urinary Incontinence.

PMID- 29637935
TI  - Correction: Understanding the needs of professionals who provide psychosocial
      care for children and adults with disorders of sex development.
AB  - [This corrects the article DOI: 10.1136/bmjpo-2017-000132.][This corrects the
      article DOI: 10.1136/bmjpo-2017-000132.].

PMID- 29637936
TI  - Mepolizumab for the treatment of eosinophilic granulomatosis with polyangiitis.
AB  - Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare but potentially
      life-threatening antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis
      which affects, to varying degrees, the lungs, paranasal sinuses, heart, kidneys,
      skin and peripheral nervous system. It is strongly associated with asthma.
      Peripheral eosinophilia is a defining feature of EGPA and eosinophilic
      inflammation is often observed in biopsies of affected tissues. Acute and chronic
      management focuses on the control of inflammation with systemic corticosteroids
      and other immunosuppressants, all of which carry a significant burden of adverse
      effects. The development of monoclonal antibody therapies against interleukin-5
      (IL-5), the major driver of eosinophilic inflammation, has therefore garnered
      significant interest among clinicians treating EGPA, who are hopeful that the
      targeted antieosinophilic effects of such drugs observed in large-scale asthma
      studies may be replicated in EGPA cohorts. In this review we discuss the features
      of EGPA, including the current understanding of the eosinophil's role in its
      pathogenesis. We also review the evidence to date regarding the efficacy of
      mepolizumab (an anti-IL-5 monoclonal antibody) in severe eosinophilic asthma and
      the smaller evidence base regarding its efficacy in EGPA, an indication for which
      it recently received U.S. Food and Drug Administration approval. The possible
      limitations of mepolizumab in EGPA management are also considered and suggestions
      put forward regarding the issues that further studies should seek to explore.

PMID- 29637937
TI  - Immune and autoimmune-related adverse events associated with immune checkpoint
      inhibitors in cancer therapy.
AB  - The recent development of monoclonal antibodies that disinhibit the immune system
      from recognizing and attacking tumor cells has revolutionized the treatment of
      cancer. Among these agents are drugs that specifically block cytotoxic T
      lymphocyte protein 4 (CTLA-4), programmed cell death protein 1 (PD-1) and
      programmed cell death 1 ligand 1 (PD-L1) signaling, called immune checkpoint
      inhibitors (ICIs). While these agents are generally well tolerated, ICI therapy
      can lead to loss of self-tolerance and the development of autoimmunity,
      manifesting as immune-related adverse events (IRAEs). Although potentially linked
      to increased antitumor responses, the morbidity associated with IRAEs can be
      significant and in rare circumstances, fatal. Virtually any organ can be affected
      and the patients present with a broad range of signs and symptoms. Moreover, ICIs
      have varying IRAEs and have distinct toxicity profiles based on their mechanism
      of action. Fortunately, most of the IRAEs can be managed with immunosuppression
      and supportive care, but contingent on early recognition and prompt treatment.
      With increasing advances in drug development, including combination ICI therapy,
      these agents are becoming one of the most prescribed oncology drugs and
      clinicians should be knowledgeable about the recognition and management of IRAEs.

PMID- 29637938
TI  - Fecal microbiota transplantation for the treatment of patients with ulcerative
      colitis and other gastrointestinal conditions beyond Clostridium difficile
      infection: an update.
AB  - Fecal microbiota transplantation (FMT) is the transplantation of microbial gut
      contents from a healthy individual into the gastrointestinal tract of a person
      with a disease, with a view to increasing the recipient's gut microbial diversity
      and bacterial richness and restoring microbial homeostasis. FMT has been proven
      to be a safe and effective treatment for Clostridium difficile infection (CDI)
      and it is now a recommended treatment for recurrent or refractory infection. FMT
      is not currently recommended for use outside of CDI due to concerns regarding
      outcome and safety; however, several case series and randomized controlled trials
      have described its use in a research environment for a few gastrointestinal
      conditions related to intestinal dysbiosis including ulcerative colitis (UC),
      Crohn's disease (CD) and irritable bowel syndrome (IBS). The most successful
      reports of the clinical efficacy of FMT in gastrointestinal conditions outside of
      CDI have been in treating UC. We summarize the current literature regarding the
      use of FMT in UC, including methodology, clinical efficacy and safety concerns,
      and identify pitfalls and areas for future development. We also describe the
      available evidence to date on the use of FMT in CD, IBS and other conditions
      related to intestinal dysbiosi.

PMID- 29637940
TI  - Life sciences licensing deals in the fourth quarter of 2017: updates and trends.
AB  - During the fourth quarter of 2017, Cortellis Competitive Intelligence registered
      1,107 new deals (excluding mergers & acquisitions) as part of its ongoing
      coverage of licensing activity in the life sciences sector compared to 1,043 in
      the third quarter and 1,035 in the fourth quarter of 2016.

PMID- 29637941
TI  - Aptamer-recognized carbohydrates on the cell membrane revealed by super
      resolution microscopy.
AB  - Carbohydrates are one of the most important components on the cell membrane,
      which participate in various physiological activities, and their aberrant
      expression is a consequence of pathological changes. In previous studies,
      carbohydrate analysis basically relied on lectins. However, discrimination
      between lectins still exists due to their multivalent character. Furthermore, the
      structures obtained by carbohydrate-lectin crosslinking confuse our direct
      observation to some extent. Fortunately, the emergence of aptamers, which are
      smaller and more flexible, has provided us an unprecedented choice. Herein, an
      aptamer recognition method with high precise localization was developed for
      imaging membrane-bound N-acetylgalactosamine (GalNAc). By using direct stochastic
      optical reconstruction microscopy (dSTORM), we compared this aptamer recognition
      method with the lectin recognition method for visualizing the detailed structure
      of GalNAc at the nanometer scale. The results indicated that GalNAc forms
      irregular clusters on the cell membrane with a resolution of 23 +/- 7 nm by
      aptamer recognition. Additionally, when treated with N-acetylgalactosidase, the
      aptamer-recognized GalNAc shows a more significant decrease in cluster size and
      localization density, thus verifying better specificity of aptamers than lectins.
      Collectively, our study suggests that aptamers can act as perfect substitutes for
      lectins in carbohydrate labeling, which will be of great potential value in the
      field of super-resolution fluorescence imaging.

PMID- 29637939
TI  - The year's new drugs & biologics, 2017, part II - News that shaped the industry
      in 2017.
AB  - This eagle's-eye overview of the drug industry in 2017 provides insight into some
      of last year's top stories, including the growing opioid crisis affecting the
      U.S. and other developed countries and the 2017-2018 influenza epidemic, with a
      spotlight on the need for a universal flu vaccine. As in previous years, we also
      review orphan drug development, new agency-supported programs such as PRIME and
      RMAT, pipeline attrition and drug pricing, as well as pharma/biotech mergers and
      acquisitions of note. Finally, we take a glimpse into the crystal ball to
      anticipate the new drugs that will be approved in 2018.

PMID- 29637942
TI  - Band bending and dipole effect at interface of metal-nanoparticles and TiO2
      directly observed by angular-resolved hard X-ray photoemission spectroscopy.
AB  - This paper describes the observation of band bending and band edge shifts at the
      interfaces between nanoscale metals and TiO2 film over a wide depth range by
      angular-resolved hard X-ray photoemission spectroscopy (HAXPES). The HAXPES
      results indicate strong electrostatic interactions between the TiO2 semiconductor
      and metal nanoparticles, while density functional theory (DFT) calculations
      suggest that these interactions are primarily associated with charge transfer
      leading to electric dipole moments at the interface in the ground state. The
      effects of these dipole moments are not limited to the surface but also occur
      deep in the bulk of the semiconductor, and are highly dependent on the coverage
      of the metal nanoparticles on the semiconductor species.

PMID- 29637943
TI  - The pH-dependent elastic properties of nanoscale DNA films and the resultant
      bending signals for microcantilever biosensors.
AB  - The diverse mechanical properties of nanoscale DNA films on solid substrates have
      a close correlation with complex detection signals of micro-/nano-devices. This
      paper is devoted to formulating several multiscale models to study the effect of
      pH-dependent ionic inhomogeneity on the graded elastic properties of nanoscale
      DNA films and the resultant bending deflections of microcantilever biosensors.
      First, a modified inverse Debye length is introduced to improve the classical
      Poisson-Boltzmann equation for the electrical potential of DNA films to consider
      the inhomogeneous effect of hydrogen ions. Second, the graded characteristics of
      the particle distribution are taken into consideration for an improvement in
      Parsegian's mesoscopic potential for both attraction-dominated and repulsion
      dominated films. Third, by the improved interchain interaction potential and the
      thought experiment about the compression of a macroscopic continuum DNA bar, we
      investigate the diversity of the elastic properties of single-stranded DNA
      (ssDNA) films due to pH variations. The relevant theoretical predictions
      quantitatively or qualitatively agree well with the relevant DNA experiments on
      the electrical potential, film thickness, condensation force, elastic modulus,
      and microcantilever deflections. The competition between attraction and repulsion
      among the fixed charges and the free ions endows the DNA film with mechanical
      properties such as a remarkable size effect and a non-monotonic behavior, and a
      negative elastic modulus is first revealed in the attraction-dominated ssDNA
      film. There exists a transition between the pH-sensitive parameter interval and
      the pH-insensitive one for the bending signals of microcantilevers, which is
      predominated by the initial stress effect in the DNA film.

PMID- 29637944
TI  - Extra thermo- and water-stable one-dimensional organic-inorganic hybrid
      perovskite [N-methyldabconium]PbI3 showing switchable dielectric behaviour,
      conductivity and bright yellow-green emission.
AB  - Haloplumbate-based perovskites display promising functionalities for advanced
      photovoltaic, optoelectronic and other applications with high performances and
      low costs. Herein, we present a study of variable-temperature crystal structures,
      dielectrics and conductance at 153-513 K, and luminescence at ambient temperature
      for a one-dimensional organic-inorganic perovskite, [N-methyldabconium]PbI3 (1).
      Hybrid 1 shows extra thermo- and water-stability (thermal decomposition at ca.
      653 K), switchable dielectric behaviour and conductance at around 348 K, owing to
      symmetry-breaking structure phase transition from the hexagonal space group
      P63/mmc in the high-temperature phase to the orthogonal space group Pcba in the
      low-temperature phase, and bright yellow-green emission at room temperature,
      originating from the electron transition within the semiconducting {PbI3}infinity
      chains. This study will broaden the scope of lead halide-based hybrid materials
      for practical application in optical and electrical devices.

PMID- 29637945
TI  - Drop spreading and gelation of thermoresponsive polymers.
AB  - Spreading and solidification of liquid droplets are elementary processes of
      relevance for additive manufacturing. Here we investigate the effect of heat
      transfer on spreading of a thermoresponsive solution (Pluronic F127) that
      undergoes a sol-gel transition above a critical temperature Tm. By controlling
      the concentration of Pluronic F127 we systematically vary Tm, while also imposing
      a broad range of temperatures of the solid and the liquid. We subsequently
      monitor the spreading dynamics over several orders of magnitude in time and
      determine when solidification stops the spreading. It is found that the main
      parameter is the difference between the substrate temperature and Tm, pointing to
      a local mechanism for arrest near the contact line. Unexpectedly, the spreading
      is also found to stop below the gelation temperature, which we attribute to a
      local enhancement in polymer concentration due to evaporation near the contact
      line.

PMID- 29637946
TI  - Stemmed DNA nanostructure for the selective delivery of therapeutics.
AB  - DNA has emerged as a biocompatible biomaterial that may be considered for various
      applications. Here, we report tumor cell-specific aptamer-modified DNA
      nanostructures for the specific recognition and delivery of therapeutic chemicals
      to cancer cells. Protein tyrosine kinase (PTK)7-specific DNA aptamer sequences
      were linked to 15 consecutive guanines. The resulting aptamer-modified product,
      AptG15, self-assembled into a Y-shaped structure. The presence of a G-quadruplex
      at AptG15 was confirmed by circular dichroism and Raman spectroscopy. The utility
      of AptG15 as a nanocarrier of therapeutics was tested by loading the
      photosensitizer, methylene blue (MB), to the G-quadruplex as a model drug. The
      generated MB-loaded AptG15 (MB/AptG15) showed specific and enhanced uptake to
      CCRF-CEM cells, which overexpress PTK7, compared with Ramos cells, which lack
      PTK7, or CCRF-CEM cells treated with a PTK7-specific siRNA. The therapeutic
      activity of MB/AptG15 was tested by triggering its photodynamic effects. Upon 660
      nm light irradiation, MB/AptG15 showed greater reactive oxygen species generation
      and anticancer activity in PTK7-overexpressing cells compared to cells treated
      with MB alone, those treated with AptG15, and other comparison groups. AptG15
      stemmed DNA nanostructures have significant potential for the cell-type-specific
      delivery of therapeutics, and possibly for the molecular imaging of target cells.

PMID- 29637947
TI  - Coordination ability determined transition metal ions substitution of Tb in Tb
      Asp fluorescent nanocrystals and a facile ions-detection approach.
AB  - Although the synthesis and fluorescent properties of lanthanide-amino acid
      complex nanostructures have been investigated extensively, limited studies have
      been reported on metal ions' substitution ability for the lanthanide ions in the
      complex and their effect on the fluorescent property. In this study, taking
      biocompatible Tb-aspartic acid (Tb-Asp) complex nanocrystals as a model, the
      substitution mechanism of metal ions, particularly transition metals, for Tb ions
      in Tb-Asp nanocrystals and the change in the fluorescent property of the Tb-Asp
      nanocrystals after substitution were systematically investigated. The
      experimental results illustrated that metal ions with higher electronegativity,
      higher valence, and smaller radius possess stronger ability for Tb ions'
      substitution in Tb-Asp nanocrystals. Based on the effect of substituting ions'
      concentration on the fluorescent property of Tb-Asp, a facile method for copper
      ions detection with high sensitivity was proposed by measuring the fluorescent
      intensity of Tb-Asp nanocrystals' suspensions containing different concentrations
      of copper ions. The good biocompatibility, great convenience of synthesis and
      sensitive detection ability make Tb-Asp nanocrystals a very low cost and
      effective material for metal ions detection, which also opens a new door for
      practical applications of metal-Asp coordinated nanocrystals.

PMID- 29637948
TI  - Encapsulation of ionic nanoparticles produces reactive oxygen species (ROS)
      responsive microgel useful for molecular detection.
AB  - Encapsulation of ionic nanoparticles in a hydrogel microparticle, i.e. microgel,
      produces a target-stimulated probe for molecular detection. Selective reactive
      oxygen species (ROS) release the enclosed cations from the microgel which
      subsequently turn on the fluorogenic dyes to emit intense fluorescence,
      permitting rapid detection of ROS or ROS-producing molecules. The ROS-responsive
      microgel provides the advantages of simple fabrication, bright and stable
      signals, easy handling, and rapid response, carrying great promise in biomedical
      applications.

PMID- 29637949
TI  - Sensitive and simultaneous surface plasmon resonance detection of free and p53
      bound MDM2 proteins from human sarcomas.
AB  - Murine double minute 2 (MDM2) is an oncoprotein mediating the degradation of the
      tumor suppressor p53 protein. The physiological levels of MDM2 protein are
      closely related to malignant transformation and tumor growth. In this work, the
      simultaneous and label-free determination of free and p53-bound MDM2 proteins
      from sarcoma tissue extracts was conducted using a dual-channel surface plasmon
      resonance (SPR) instrument. Free MDM2 protein was measured in one fluidic channel
      covered with the consensus double-stranded (ds)-DNA/p53 conjugate, while MDM2
      bound to p53 was captured by the consensus ds-DNA immobilized onto the other
      channel. To achieve higher sensitivity and to confirm specificity, an MDM2
      specific monoclonal antibody (2A10) was used to recognize both the free and p53
      bound MDM2 proteins. The resultant method afforded a detection limit of 0.55 pM
      of MDM2. The amenability of the method to the analysis of free and p53-bound MDM2
      proteins was demonstrated for normal and sarcoma tissue extracts from three
      patients. Our data reveal that both free and total MDM2 (free and bound forms
      combined) proteins from sarcoma tissue extracts are of much higher concentrations
      than those from normal tissue extracts and the p53-bound MDM2 protein only
      constitutes a small fraction of the total MDM2 concentration. In comparison with
      enzyme-linked immunosorbent assay (ELISA), the proposed method possesses higher
      sensitivity, is more cost-effective, and is capable of determining free and p53
      bound MDM2 proteins in clinical samples.

PMID- 29637950
TI  - Phosphate glasses via coacervation route containing CdFe2O4 nanoparticles:
      structural, optical and magnetic characterization.
AB  - CdFe2O4 nanoparticles of around 3.9 nm were synthesized using the coprecipitation
      method and protected by a silica layer. The nanoparticles were mixed with a
      coacervate and transformed into phosphate glasses with 1, 4 and 8% in mass of
      nanoparticles by the melt-quenching method. TEM images confirm that the
      nanoparticles were successfully incorporated into the matrix without inducing
      crystallization. 31P NMR and Raman spectral analyses show that new P-O-Si bonds
      are formed in the glasses containing nanoparticles. The glass transition
      increases as a function of the nanoparticle content due to an increase in the
      connectivity of the phosphate glass chains. The UV-Vis spectra show bands at 415
      and 520 nm assigned to Fe3+ ions and at 1025 nm, characteristic of Fe2+ ions,
      indicating that some of the nanoparticles dissolve during the melting process.
      The sample with 8% CdFe2O4 presents a paramagnetic behavior. The glasses obtained
      are transparent, non-hygroscopic and possess enormous thermal stability which is
      important for the production of optical devices.

PMID- 29637951
TI  - Nanocluster superstructures or nanoparticles? The self-consuming scaffold
      decides.
AB  - We show that using the same reaction procedure, by hindering or allowing the
      formation of a reaction intermediate, the Ag+dodecanethiolate polymeric complex,
      it is possible to selectively obtain Ag dodecanethiolate nanoparticles or Ag
      dodecanethiolate nanoclusters in the size range 4-2 nm. Moreover, the Ag
      dodecanethiolate nanoclusters display a lamellar superstructure templated from
      the precursor Ag+dodecanethiolate polymeric complex. A plausible formation
      mechanism is illustrated where, starting from the precursor and scaffold lamellar
      Ag+ thiolate polymeric complex, first the nanocluster Agn0 core is formed by
      reduction of isoplanar Ag+ ions, followed by Ag+ thiolate units that build
      protection, the nanocluster shell, around the core. The nanoclusters are
      characterized by elemental analyses, XRD, ATR-FTIR, XPS, XAS, MALDI, ESI, UV-Vis
      and fluorescence measurements. The luminescent Ag15(dodecanethiolate)11.2H2O
      nanocluster is achieved in good yield after 4 hours of reaction whereas after 2
      hours, the luminescent Ag35(dodecanethiolate)16 is isolated. Both Ag nanoclusters
      present emission bands in the range 330-450 nm, the shifting depending on the
      excitation wavelength. This phenomenon is attributed to a possible dipolar state
      causing distribution in energies due to variability of dipole-dipole
      interactions. Moreover, both nanoclusters further present a NIR emission at about
      700 nm independent from the excitation wavelength. Thanks to their optical and
      structural properties, the synthesized nanoclusters, perfect
      molecular/nanoparticle hybrids, have great potentiality for new applications in
      nanotechnologies.

PMID- 29637952
TI  - Elucidating ultrafast electron dynamics at surfaces using extreme ultraviolet
      (XUV) reflection-absorption spectroscopy.
AB  - Here we review the recent development of extreme ultraviolet reflection
      absorption (XUV-RA) spectroscopy. This method combines the benefits of X-ray
      absorption spectroscopy, such as element, oxidation, and spin state specificity,
      with surface sensitivity and ultrafast time resolution, having a probe depth of
      only a few nm and an instrument response less than 100 fs. Using this technique
      we investigated the ultrafast electron dynamics at a hematite (alpha-Fe2O3)
      surface. Surface electron trapping and small polaron formation both occur in 660
      fs following photoexcitation. These kinetics are independent of surface
      morphology indicating that electron trapping is not mediated by defects. Instead,
      small polaron formation is proposed as the likely driving force for surface
      electron trapping. We also show that in Fe2O3, Co3O4, and NiO, band gap
      excitation promotes electron transfer from O 2p valence band states to metal 3d
      conduction band states. In addition to detecting the photoexcited electron at the
      metal M2,3-edge, the valence band hole is directly observed as transient signal
      at the O L1-edge. The size of the resulting charge transfer exciton is on the
      order of a single metal-oxygen bond length. Spectral shifts at the O L1-edge
      correlate with metal-oxygen bond covalency, confirming the relationship between
      valence band hybridization and the overpotential for water oxidation. These
      examples demonstrate the unique ability to measure ultrafast electron dynamics
      with element and chemical state resolution using XUV-RA spectroscopy.
      Accordingly, this method is poised to play an important role to reveal chemical
      details of previously unseen surface electron dynamics.

PMID- 29637953
TI  - Oxidation of substituted aromatic hydrocarbons in the tropospheric aqueous phase:
      kinetic mechanism development and modelling.
AB  - Monocyclic aromatic compounds are ubiquitous in the polluted troposphere and
      contribute to the formation of tropospheric ozone and anthropogenic secondary
      organic aerosol, including brown carbon. Currently available physico-chemical
      data including aqueous-phase kinetic and mechanistic data, as well as phase
      transfer parameters have been compiled and reviewed, to construct a novel aqueous
      phase oxidation mechanism for monocyclic aromatic compounds. The performed
      chemical mechanism development results in a comprehensive aqueous-phase oxidation
      mechanism (addressed as CAPRAM-AM1.0), which includes 292 processes considering
      the oxidation of different aromatic compounds. Detailed numerical simulations
      with the air parcel model SPACCIM are carried out for different urban
      environmental and seasonal conditions. Results show that the aqueous-phase
      chemistry of aromatic compounds, particularly in clouds, increases the organic
      aerosol mass by up to 10% in total. The absolute contribution to aqSOA in
      summertime is modelled to be 260 ng m-3 and 1.2 MUg m-3 under moderate and
      strongly polluted conditions, respectively. Aqueous-phase oxidations of aromatic
      compounds are important not only for the degradation, but also for the formation
      of nitrated aromatic compounds. In-cloud chemistry contributes up to 54% to the
      nitrocatechol oxidation and up to 37% to its formation under polluted
      tropospheric conditions. Besides, nitrated aromatic compounds contribute up to
      5.4 MUg m-3 to modelled brown carbon concentration in cloud droplets and 140 ng m
      3 in aerosol particles. Further, the model simulations indicate that besides OH
      radical oxidations, aromatic compounds with two hydroxyl groups are also strongly
      oxidised by O3 and HO2. O3 contributes with 49% to 68% and HO2 with 19% to 22% to
      the aqueous-phase oxidation of catechol under moderate and strong polluted
      environmental conditions studied.

PMID- 29637954
TI  - Forces, energetics, and dynamics of conjugated-carbon ring tethers adhered to
      CNTs: a computational investigation.
AB  - The strength and nature of the interactions between carbon nanotubes (CNTs) and
      molecular tethers plays a vital role in technology such as CNT-enzyme sensors.
      Tethers that attach noncovalently to CNTs are ideal for retaining the electrical
      properties of the CNTs since they do not degrade the CNT surface and effect its
      electrical conductivity. However, leaching due to weak CNT-tether attachment is
      very common when using noncovalent tethers, and this has limited their use in
      commercial products including biosensors. Thus, understanding the fundamental
      mechanics governing the strength of CNT-tether adhesion is crucial for the design
      of highly sensitive, viable sensors. Here, we computationally investigate the
      adhesion strength of CNT-tether complexes with 8 different tethering molecules
      designed to adhere noncovalently to the CNT surface. We study the effects of CNT
      diameter, CNT chirality, and the size/geometry of the tethering molecule on the
      adhesion energy and force. Our results show an asymptotic relationship between
      adhesion strength and CNT diameter. Calculations show that noncovalent tethers
      tested here can reach adhesion forces and energies that are up to 21% and 54% of
      the strength of the carbon-carbon single bond force and bond energy respectively.
      We anticipate our results will help guide CNT-enzyme sensor design to produce
      sensors with high sensitivity and minimal leaching.

PMID- 29637956
TI  - Self-propagated combustion synthesis of few-layered graphene: an optical
      properties perspective.
AB  - This paper describes a labour efficient and cost-effective strategy to prepare
      few-layered of reduced graphene oxide like (RGOL) sheets from graphite. The self
      propagated combustion route enables the bulk production of RGOL sheets.
      Microscopic and spectroscopic analyses confirmed the formation of few-layer
      graphene sheets of an average thickness of ~3 nm and the presence of some oxygen
      functional groups with a C/O ratio of 8.74. A possible mechanistic pathway for
      the formation of RGOL sheets is proposed. The optical properties of the RGOL
      sample were studied in detail by means of Spectroscopic Ellipsometry (SE). The
      experimental abilities of SE in relating the optical properties with the number
      of oxygen functionalities present in the samples are explored. The data were
      analysed by a double-layered optical model along with the Drude-Lorentz
      oscillatory dispersion relation. The refractive index (n = 2.24), extinction
      coefficient (k = 2.03), and dielectric functions are obtained using point-by
      point analysis and are also checked for Kramers-Kronig (KK) consistency.

PMID- 29637955
TI  - Co-solvent effects on reaction rate and reaction equilibrium of an enzymatic
      peptide hydrolysis.
AB  - This work presents an approach that expresses the Michaelis constant KaM and the
      equilibrium constant Kth of an enzymatic peptide hydrolysis based on
      thermodynamic activities instead of concentrations. This provides KaM and Kth
      values that are independent of any co-solvent. To this end, the hydrolysis
      reaction of N-succinyl-l-phenylalanine-p-nitroanilide catalysed by the enzyme
      alpha-chymotrypsin was studied in pure buffer and in the presence of the co
      solvents dimethyl sulfoxide, trimethylamine-N-oxide, urea, and two salts. A
      strong influence of the co-solvents on the measured Michaelis constant (KM) and
      equilibrium constant (Kx) was observed, which was found to be caused by molecular
      interactions expressed as activity coefficients. Substrate and product activity
      coefficients were used to calculate the activity-based values KaM and Kth for the
      co-solvent free reaction. Based on these constants, the co-solvent effect on KM
      and Kx was predicted in almost quantitative agreement with the experimental data.
      The approach presented here does not only reveal the importance of understanding
      the thermodynamic non-ideality of reactions taking place in biological solutions
      and in many technological applications, it also provides a framework for
      interpreting and quantifying the multifaceted co-solvent effects on enzyme
      catalysed reactions that are known and have been observed experimentally for a
      long time.

PMID- 29637957
TI  - (Poly)cation-induced protection of conventional and wireframe DNA origami
      nanostructures.
AB  - DNA nanostructures hold immense potential to be used for biological and medical
      applications. However, they are extremely vulnerable towards salt depletion and
      nucleases, which are common under physiological conditions. In this contribution,
      we used chitosan and linear polyethyleneimine for coating and long-term
      stabilization of several three-dimensional DNA origami nanostructures. The impact
      of the degree of polymerization and the charge density of the polymer together
      with the N/P charge ratio (ratio of the amines in polycations to the phosphates
      in DNA) on the stability of encapsulated DNA origami nanostructures in the
      presence of nucleases and in low-salt media was examined. The polycation shells
      were compatible with enzyme- and aptamer-based functionalization of the DNA
      nanostructures. Additionally, we showed that despite being highly vulnerable to
      salt depletion and nucleolytic digestion, self-assembled DNA nanostructures are
      stable in cell culture media up to a week. This was contrary to unassembled DNA
      scaffolds that degraded in one hour, showing that placing DNA strands into a
      spatially designed configuration crucially affect the structural integrity. The
      stability of naked DNA nanostructures in cell culture was shown to be mediated by
      growth media. DNA origami nanostructures kept in growth media were significantly
      more resistant towards low-salt denaturation, DNase I and serum-mediated
      digestion than when in a conventional buffer. Moreover, we confirmed that DNA
      origami nanostructures remain not only structurally intact but also fully
      functional after exposure to cell media. Agarose gel electrophoresis and negative
      stain transmission electron microscopy analysis revealed the hybridization of DNA
      origami nanostructures to their targets in the presence of serum proteins and
      nucleases. The structural integrity and functionality of DNA nanostructures in
      physiological fluids validate their use particularly for short-time biological
      applications in which the shape and structural details of DNA nanodevices are
      functionally critical.

PMID- 29637958
TI  - Visualizing a core-shell structure of heavily doped silicon quantum dots by
      electron microscopy using an atomically thin support film.
AB  - We successfully visualize a core-shell structure of a heavily B and P codoped Si
      quantum dot (QD) by transmission electron microscopy using an ultra-thin graphene
      oxide support film. The enhanced contrast reveals that a codoped Si QD has a
      highly crystalline Si core and an amorphous shell composed of Si, B and P.

PMID- 29637959
TI  - Stable micelles based on a mixture of coiled-coils: the role of different
      oligomeric states.
AB  - Homomeric micelles with tunable size, shape and stability have been extensively
      studied for biomedical applications such as drug carriers. However, designing the
      local valency and self-assembled morphology of nanophase-separated multicomponent
      micelles with varied ligand binding possibilities remains challenging. Here, we
      present micelles self-assembled from amphiphilic peptide-PEG-lipid hybrid
      conjugates, where the peptides can be either a 3-helix or 4-helix coiled-coil. We
      demonstrate that the micelle size and sphericity can be controlled based on the
      coiled-coil oligomeric state. Using theory and coarse-grained dissipative
      particle dynamics (DPD) simulations in an explicit solvent simulation, we studied
      the distribution of 3-helix and 4-helix conjugates within the mixed micelles and
      observed self-organization into nanodomains within the mixed micelle. We
      discovered that the phase separation behavior is dictated by the geometry
      mismatch in the alkyl chain length from different coiled-coil oligomeric states.
      Our analyses of the self-assembly tendency and drug delivery potency of mixed
      micelles with controlled multivalency provide important insights into the
      assembly and formation of nanophase-separated micelles.

PMID- 29637960
TI  - The reductive aromatization of naphthalene diimide: a versatile platform for 2,7
      diazapyrenes.
AB  - The reductive aromatization of naphthalene diimide provides tetrapivaloxy-2,7
      diazapyrene, which serves as a versatile platform toward peripherally substituted
      2,7-diazapyrenes. Time-resolved microwave conductivity measurements demonstrated
      that the intrinsic electron mobility of 2,7-diazapyrene is significantly higher
      than that of the corresponding pyrene.

PMID- 29637961
TI  - Humidity- and light-driven actuators based on carbon nanotube-coated paper and
      polymer composite.
AB  - Multi-responsive actuators driven by different stimuli (e.g. light, humidity,
      electricity) have attracted intense attention recently for the advantages of
      being used in various environments and show enormous actuation. In this work, we
      propose humidity- and light-driven actuators based on carbon nanotube (CNT)
      coated paper and a biaxially oriented polypropylene (BOPP) composite. The CNT
      paper/BOPP actuator shows large bending actuation when driven by humidity change
      (curvature of 1.2 cm-1) and near infrared (NIR) light irradiation (curvature up
      to 1.6 cm-1). The great actuation performances outperform most other paper-based
      actuators. Finally, a smart gripper, of which the initial opening width can be
      enlarged, is fabricated on the basis of the CNT-paper/BOPP actuators. By
      utilizing the bidirectional bending motion of the actuator, the opening width of
      the gripper can increase to a width that is 4 times larger than its initial
      width, so as to grasp a large object. The gripper is also able to raise and move
      an object that is 20 times heavier than one actuator of the gripper. We assume
      that this new type of actuator has great potential in artificial muscle, soft
      robotics and biomimetic applications.

PMID- 29637962
TI  - Direct observation of Ru-alkylidene forming into ethylene in ring-closing
      metathesis from hyperpolarized 1H NMR.
AB  - Ring-closing metathesis was monitored using real-time NMR of 1H hyperpolarized
      olefins at room temperature. By applying a selective saturation to an observable
      intermediate, its protons were found to transfer to ethylene. The intermediate
      was thus identified as a Ru-alkylidene species, which appears in the ethylene
      formation pathway.

PMID- 29637963
TI  - Tuning the plasmonic response of TiN nanoparticles synthesised by the transferred
      arc plasma technique.
AB  - Titanium nitride exhibits plasmonic behaviour in the visible and NIR region.
      Combined with a refractory nature, it can be an attractive alternate plasmonic
      material useful in many applications. Despite the plethora of methods to produce
      TiN nanoparticles, it remains challenging to generate high quality TiN
      nanoparticles efficiently. Here we demonstrate the transferred arc plasma
      technique as a viable way to synthesise TiN nanoparticles. We show here that
      modulating the processing conditions can control the optical properties and tune
      the plasmonic response rendering the application of TiN nanoparticles viable
      across many applications.

PMID- 29637964
TI  - Orienting proteins by nanostructured surfaces: evidence of a curvature-driven
      geometrical resonance.
AB  - Experimental and theoretical reports have shown that nanostructured surfaces have
      a dramatic effect on the amount of protein adsorbed and the conformational state
      and, in turn, on the performances of the related devices in tissue engineering
      strategies. Here we report an innovative method to prepare silica-based
      nanostructured surfaces with a reproducible, well-defined local curvature,
      consisting of ordered hexagonally packed arrays of curved hemispheres, from
      nanoparticles of different diameters (respectively 147 nm, 235 nm and 403 nm).
      The nanostructured surfaces have been made chemically homogeneous by partially
      embedding silica nanoparticles in poly(hydroxymethylsiloxane) films, further
      modified by means of UV-O3 treatments. This paper has been focused on the
      experimental and theoretical study of laminin, taken as a model protein, to study
      the nanocurvature effects on the protein configuration at nanostructured
      surfaces. A simple model, based on the interplay of electrostatic interactions
      between the charged terminal domains of laminin and the nanocurved charged
      surfaces, closely reproduces the experimental findings. In particular, the model
      suggests that nanocurvature drives the orientation of rigid proteins by means of
      a "geometrical resonance" effect, involving the matching of dimensions, charge
      distribution and spatial arrangement of both adsorbed molecules and adsorbent
      nanostructures. Overall, the results pave the way to unravel the nanostructured
      surface effects on the intra- and inter-molecular organization processes of
      proteins.

PMID- 29637965
TI  - Products and mechanism of the OH-initiated photo-oxidation of perfluoro ethyl
      vinyl ether, C2F5OCF[double bond, length as m-dash]CF2.
AB  - The OH-initiated photo-oxidation of perfluoro ethyl vinyl ether (C2F5OCF[double
      bond, length as m-dash]CF2, PEVE) in air (298 K, 50 and 750 Torr total pressure)
      was studied in a photochemical reactor using in situ detection of PEVE and its
      products by Fourier transform IR absorption spectroscopy. The relative rate
      technique was used to derive the rate coefficient, k1, for the reaction of PEVE
      with OH as k1 = (2.8 +/- 0.3) * 10-12 cm3 molecule-1 s-1. The photo-oxidation of
      PEVE in the presence of NOx at 1 bar results in formation of C2F5OCFO, FC(O)C(O)F
      and CF2O in molar yields of 0.50 +/- 0.07, 0.46 +/- 0.07 and 1.50 +/- 0.22,
      respectively. FC(O)C(O)F and CF2O are formed partially in secondary, most likely
      heterogeneous processes. At a reduced pressure of 50 Torr, the product
      distribution is shifted towards formation of FC(O)C(O)F, indicating the important
      role of collisional quenching of initially formed association complexes, and
      enabling details of the reaction mechanism to be elucidated. An atmospheric photo
      oxidation mechanism for PEVE is presented and the environmental implications of
      PEVE release and degradation are discussed.

PMID- 29637966
TI  - Singular wavelength dependence on the sensitization of lanthanides by graphene
      quantum dots.
AB  - In this manuscript, we study the sensitization of Tb3+ ions by the excited state
      of GQD. We found that Tb3+ cations can bind to GQDs and display
      photoluminescence. Excitation dependent experiments show that the Tb3+ emission
      is stronger at shorter excitation wavelengths, which is likely due to pseudo
      isolated small aromatic moieties produced during the synthesis of the GQDs.

PMID- 29637967
TI  - An etching-assisted route for fast and large-scale fabrication of non-layered
      palladium nanosheets.
AB  - To date, great progress has been made in the shape-controlled synthesis of noble
      metal nanocrystals. However, there still exists a major gap between academic
      studies and industrial applications due to the inability to produce nanocrystals
      in large quantities while retaining their uniformity. To help fill this gap,
      herein, we provide a new route to scale up and accelerate the production of non
      layered palladium nanosheets (Pd NSs) by incorporating etching while retaining
      effective capping during the synthesis. The key to this rapid synthesis is the
      etching induced by selected etchants (e.g., Fe3+/Fe2+, Cl-/O2, Br-/O2, and I
      /O2). Specifically, this synthesis can be accomplished within 3 min, reaching a
      yield as high as 7.2 g L-1 h-1. The thickness of Pd NSs can be tuned to 1.6, 2.0,
      2.3, and 3.5 nm by controlling the etching and reducing rates via choosing
      different type of etchants. Moreover, these non-layered Pd NSs are fabricated in
      an aqueous solution without the addition of any organic compounds; therefore, the
      surface of these NSs is extremely clean. When used as a catalyst for the formic
      acid oxidation reaction, the as-prepared non-layered Pd NSs exhibit a mass
      activity as high as 1350 mA mg-1, which is 3.7 times higher than that of
      commercial Pd/C, due to their much larger electrochemical surface area (66.2 m2 g
      1, which is 2.7 times higher than that of commercial Pd/C).

PMID- 29637968
TI  - The structural isomerism in gold nanoclusters.
AB  - The isomerism in thiolate-protected gold (Au) nanoclusters is important for the
      understanding of structure-property correlations and the design of Au
      nanoclusters with specific structures and properties. Although recent studies
      have identified stereoisomerism, the understanding of structural isomerism is
      still lacking. Herein, we identified three distinct mechanisms of structural
      isomerism (i.e., core isomerism, staple isomerism, and complex isomerism) based
      on the crystallized isomers of thiolate-protected Au nanoclusters, and these
      mechanisms can be viewed as analogous to those of the structural isomerism in
      organic molecules (i.e., chain isomerism, point isomerism, and functional
      isomerism). Using the discovered core isomerism and staple isomerism, two
      Au28(SR)20 isomers are predicted and their synthesis feasibilities are
      illuminated. These new insights into the structural isomerism can facilitate
      rational design of new isomers of thiolate-protected Au nanoclusters and guide
      future experimental synthesis.

PMID- 29637969
TI  - Unconventional two-dimensional germanium dichalcogenides.
AB  - The recently discovered two-dimensional (2D) group IV chalcogenides attract much
      attention owing to their novel electronic and photonic properties. All the
      reported materials of this class favor (distorted) octahedral coordination via p
      bonding; by contrast, in the dichalcogenides where the bonding tendency
      approaches sp3, no corresponding 2D phase has been realized so far. Here, by
      engineering the composition of a chalcogenide heterostructure, the hitherto
      elusive GeTe2 is experimentally observed in a confined 2D environment. Density
      functional theory simulations predict the existence of a freestanding monolayer
      of octahedrally coordinated GeTe2 under tensile strain, and the existence of
      GeSe2 and GeS2 in the same form under equilibrium conditions. These 2D germanium
      dichalcogenides are either metallic or narrow gap semiconducting, and may lead to
      new applications in nanoscale electronics.

PMID- 29637971
TI  - MoS2 nano flakes with self-adaptive contacts for efficient thermoelectric energy
      harvesting.
AB  - We examine the potential of the low-dimensional material MoS2 for the efficient
      conversion of waste heat to electricity via the Seebeck effect. Recently
      monolayer MoS2 nano flakes with self-adaptive Mo6S6 contacts were formed, which
      take advantage of mechanical stability and chemical covalent bonding to the MoS2.
      Here, we study the thermoelectric properties of these junctions by calculating
      their conductance, thermopower and thermal conductance due to both electrons and
      phonons. We show that thermoelectric figures of merit ZT as high as ~2.8 are
      accessible in these junctions, independent of the flake size and shape, provided
      the Fermi energy is close to a band edge. We show that Nb dopants as substituents
      for Mo atoms can be used to tune the Fermi energy, and despite the associated
      inhomogeneous broadening, room temperature values as high as ZT ~ 0.6 are
      accessible, increasing to 0.8 at 500 K.

PMID- 29637970
TI  - Silver nanowires for highly reproducible cantilever based AFM-TERS microscopy:
      towards a universal TERS probe.
AB  - Tip-enhanced Raman scattering (TERS) microscopy is a unique analytical tool to
      provide complementary chemical and topographic information of surfaces with
      nanometric resolution. However, difficulties in reliably producing the necessary
      metallized scanning probe tips has limited its widespread utilisation,
      particularly in the case of cantilever-based atomic force microscopy. Attempts to
      alleviate tip related issues using colloidal or bottom-up engineered tips have so
      far not reported consistent probes for both Raman and topographic imaging. Here
      we demonstrate the reproducible fabrication of cantilever-based high-performance
      TERS probes for both topographic and Raman measurements, based on an approach
      that utilises noble metal nanowires as the active TERS probe. The tips show 10
      times higher TERS contrasts than the most typically used electrochemically-etched
      tips, and show a reproducibility for TERS greater than 90%, far greater than
      found with standard methods. We show that TERS can be performed in tapping as
      well as contact AFM mode, with optical resolutions around or below 15 nm, and
      with a maximum resolution achieved in tapping-mode of 6 nm. Our work illustrates
      that superior TERS probes can be produced in a fast and cost-effective manner
      using simple wet-chemistry methods, leading to reliable and reproducible high
      resolution and high-sensitivity TERS, and thus renders the technique applicable
      for a broad community.

PMID- 29637972
TI  - On the evaporation kinetics of [60] fullerene in aromatic organic solvents.
AB  - We investigate the effect of C60 fullerene nanospheres on the evaporation
      kinetics of a number of aromatic solvents with different levels of molecular
      association, namely, benzene, toluene, and chlorobenzene. The dependence of the
      evaporation rate on the fullerene concentration is not monotonic but rather
      exhibits maxima and minima. The results strongly support the notion of molecular
      structuring within the liquid solvent controlled by the nature of the
      fullerene/solvent interaction and the level of molecular association within the
      solvent itself.

PMID- 29637973
TI  - A chemical/molecular 4-input/2-output keypad lock with easy resettability based
      on red-emission carbon dots-Prussian blue composite film electrodes.
AB  - In this work, a resettable 4-input/2-output keypad lock system based on red
      emission carbon dots (rCDs) and Prussian blue (PB) modified electrodes was
      developed. Electrochromic PB layers were first electrochemically deposited on the
      indium tin oxide (ITO) electrode surface. An admixture of rCDs and chitosan (Chi)
      was then cast on the surface of PB layers, forming rCDs-Chi/PB film electrodes.
      UV-vis absorption of the films was sensitive to the applied potential since the
      blue PB constituent of the films would be transformed to nearly colorless
      Prussian white (PW) at the reduction potential of -0.2 V and then from PW back to
      PB at the oxidation potential of 0.4 V, and the transformation between PB and PW
      would also influence the fluorescence emission of the rCD constituent in the
      films. The addition of cysteine (Cys) in the testing solution could reduce the PB
      in the films into PW and generate an amperometric electrocatalytic current at 0.4
      V. Meanwhile, the addition of Fe3+ in solution could greatly quench the
      fluorescence from the rCD component in the films. Thus, the responses of UV-vis
      absorbance, fluorescence emission and amperometric current of the rCDs-Chi/PB
      film electrode system exhibited potential-, Cys- and Fe3+-responsive switching
      properties. Based on the aforementioned work, a combinational logic gate circuit
      with 3 inputs and 3 outputs was established. In particular, on the same platform,
      a novel chemical/molecular 4-input/2-output keypad lock with easy resettability
      was elaborately designed with amperometric current and fluorescence peak
      intensity as two different types of outputs, so that a higher security level
      could be achieved.

PMID- 29637974
TI  - Growth of Au and ZnS nanostructures via engineered peptide and M13 bacteriophage
      templates.
AB  - We demonstrate directed nucleation of Au and ZnS patterns on templates comprised
      of functional peptides and an M13 bacteriophage. We discuss the control over
      nucleation in terms of the interplay between enhanced ion binding and reduced
      interfacial energy resulting from the presence of the templates.

PMID- 29637975
TI  - 2,3-Diaroyl benzofurans from arynes: sequential synthesis of 2-aroyl benzofurans
      followed by benzoylation.
AB  - A cascade synthetic strategy for the direct synthesis of 2-aroyl benzofurans from
      aryne precursors has been developed. This reaction proceeds via C-O and C-C bond
      cleavage as well as C-O and C-C bond formation in a single reaction vessel. The
      methodology provides good yields of 2-aroyl benzofurans and tolerates a variety
      of functional groups. The synthesized 2-aroyl benzofurans were further
      benzoylated at 3-positions and one of the synthesized 2,3-diaroyl benzofuran
      structures was confirmed unambiguously by X-ray crystallography.

PMID- 29637976
TI  - Gravitational collapse of colloidal gels: non-equilibrium phase separation driven
      by osmotic pressure.
AB  - Delayed gravitational collapse of colloidal gels is characterized by initially
      slow compaction that gives way to rapid bulk collapse, posing interesting
      questions about the underlying mechanistic origins. Here we study gel collapse
      utilizing large-scale dynamic simulation of a freely draining gel of physically
      bonded particles subjected to gravitational forcing. The hallmark regimes of
      collapse are recovered: slow compaction, transition to rapid collapse, and long
      time densification. Microstructural changes are monitored by tracking particle
      positions, coordination number, and bond dynamics, along with volume fraction,
      osmotic pressure, and potential energy. Together these reveal the surprising
      result that collapse can occur with a fully intact network, where the tipping
      point arises when particle migration dissolves strands in a capillary-type
      instability. While it is possible for collapse to rupture a gel network into
      clusters that then sediment, and hydrodynamic interactions can make interesting
      contributions, neither is necessary. Rather, we find that the "delay" arises from
      gravity-enhanced coarsening, which triggers the re-emergence of phase separation.
      The mechanism of this transition is a leap toward lower potential energy of the
      gel, driven by bulk negative osmotic pressure that condenses the particle phase:
      the gel collapses in on itself under negative osmotic pressure allowing the gel,
      to tunnel through the equilibrium phase diagram to a higher volume fraction
      "state". Remarkably, collapse stops when condensation stops, when gravitational
      advection produces a positive osmotic pressure, re-arresting the gel.

PMID- 29637977
TI  - Light-weight 3D Co-N-doped hollow carbon spheres as efficient electrocatalysts
      for rechargeable zinc-air batteries.
AB  - Rational design of cost-effective, nonprecious metal-based catalysts with a
      desirable oxygen reduction reaction (ORR) performance by a simple and economical
      synthesis route is a great challenge for the commercialization of future fuel
      cell and metal-air batteries. Herein, light-weight 3D Co-N-doped hollow carbon
      spheres (Co-NHCs) have been fabricated via a facile emulsion approach followed by
      carbonization. The prepared 0.1-Co-NHCs catalyst with suitable Co doping content
      exhibits favorable ORR catalytic activity (onset potential of 0.99 V and half
      wave potential of 0.81 V vs. RHE), comparable to that of commercial Pt-C (onset
      potential of 1.02 V and half-wave potential of 0.83 V vs. RHE) and rivals that of
      Pt-C with better cycling stability. The excellent performance of the catalyst is
      attributed to the synergetic effect of Co and N doping with a high total ratio of
      active sites, high surface area and good conductivity of the material. More
      impressively, the assembled rechargeable zinc-air batteries based on the 0.1-Co
      NHCs catalyst outperform those afforded by commercial Pt-C. The progress
      presented in this reported work is of great importance in the development of
      outstanding non-noble metal based electrocatalysts for the fuel cell and metal
      air battery industry.

PMID- 29637978
TI  - High-temperature solvent-free sulfidation of MoO3 confined in a polypyrrole
      shell: MoS2 nanosheets encapsulated in a nitrogen, sulfur dual-doped carbon
      nanoprism for efficient lithium storage.
AB  - Hierarchical nanostructured metal sulfides in a rectangular prism shape are
      highly attractive as a promising electrode material for lithium ion energy
      storage. Herein, we develop a simultaneous pyrolysis and sulfidation strategy to
      synthesize yolk-shelled MoS2@nitrogen, sulfur dual-doped carbon (MoS2@NSC)
      nanoprisms. Upon encapsulating MoO3 nanoprisms into a polypyrrole (PPy) shell, a
      high-temperature solvent-free sulfidation reaction from MoO3 to hierarchical MoS2
      nanosheets could take place within the PPy nanoreactor, and the PPy nanoreactor
      simultaneously converted into NSC hollow nanoprisms. Owing to the compositional
      and structural superiority, the MoS2@NSC nanoprisms with a well-defined sheet-in
      prism superstructure manifested enhanced electrochemical activity as a promising
      anode material for lithium-ion batteries including a high reversible capacity
      (960 mA h g-1 at 0.1 A g-1), excellent cycling stability (800 mA h g-1 at 0.1 A g
      1 up to 300 cycles), and superior rate capability (440 mA h g-1 at 2 A g-1).

PMID- 29637979
TI  - FT-IR- and Raman-based biochemical profiling of the early stage of pulmonary
      metastasis of breast cancer in mice.
AB  - The combination of FT-IR and Raman spectroscopies allowed the biochemical
      profiling of lungs in the early stage of pulmonary metastasis in the murine model
      of breast cancer. Histological staining was used as a reference. Raman
      spectroscopy was especially useful in the detection and semi-quantitative
      analysis of the vitamin A content in lung lipofibroblasts, whereas the IR
      technique provided semi-quantitative information on the contents of nucleic
      acids, carbohydrates including glycogen, and lipids as well as changes in the
      secondary structures of tissue proteins. Our spectroscopic results suggest that
      the early phase of metastasis in the lung is characterized by a decrease in the
      endogenous retinoid content in combination with a decrease in the content of
      glycogen and lipids.

PMID- 29637980
TI  - Transport mechanisms in a puckered graphene-on-lattice.
AB  - Understanding the fundamental properties of graphene when its topography is
      patterned by the use of a compliant substrate is essential to improve the
      performances of graphene sensors. Here we suspend a graphene monolayer on SiO2
      nanopillar arrays to form a puckered graphene-on-lattice and investigate the
      strain and electrical transport at the nanoscale. Despite a nonuniform strain in
      the graphene-on-lattice, the resistivity is governed by thermally activated
      transport and not the strain. We show that the high thermal activation energy
      results from a low charge carrier density and a periodic change of the chemical
      potential induced by the interaction of the graphene monolayer with the
      nanopillars, making the use of graphene-on-lattice attractive to further increase
      the electrical response of graphene sensors.

PMID- 29637981
TI  - Mimicking plasmonic nanolaser emission by selective extraction of electromagnetic
      near-field from photonic microcavity.
AB  - Plasmonic nanolasers have attracted significant attention owing to their ability
      to generate a coherent optical field in the deep subwavelength region, and they
      exhibit promising applications in integrated photonics, bioimaging and sensing.
      However, the demonstration of lasing in individual metallic nanoparticles with 3D
      subwavelength confinement represents a significant challenge and is yet to be
      realized. Herein, we propose to mimic a plasmonic nanolaser via selective
      scattering off the evanescent tail of a lasing photonic nanobelt using a single
      silver nanorod (24 nm * 223 nm). The nanorod acts as an optical antenna that
      selectively extracts the near-field component along the rod axis. The light
      output from the silver nanorod mimics the emission of a plasmonic nanolaser in
      its localized near-field and polarization dependence, except for the lasing
      wavelength and linewidth, which are inherited from the photonic laser. The
      realization of localized coherent light sources provides promising nanoscale
      lighting that shows potential in background-suppressed illumination, biosensing
      and imaging.

PMID- 29637986
TI  - A facile method to functionalize gold nano-tripods with high suspension stability
      in an aqueous environment.
AB  - Here we aim to develop a facile emulsion-based method to prepare tripod gold
      nanoparticles (AuNPs) with high suspension stability in an aqueous environment. A
      gyroid-structured polymer template formed by the hydrolysis of a degradable block
      copolymer, polystyrene (PS)-b-poly(l-lactide), is used for the fabrication of
      AuNPs. Also, a successful emulsification of dichloromethane (DCM) in the aqueous
      phase is developed by using thiolated polyethylene glycol (PEG-SH) as the
      stabilizer. Subsequently, the nanohybrids of PS/Au can be fabricated by templated
      electroless plating, and then selectively dissolving in the DCM dispersive phase.
      Most interestingly, a dedicated process for the simultaneous release of the
      tripod AuNPs from the dissolution of PS associated with PEG-SH at the interface
      of the emulsion is achieved, giving PEG-SH-functionalized tripod AuNPs dispersed
      in the aqueous phase, which significantly improves the suspension stabilization
      of tripod AuNPs. The in situ temperature-programmed electrospray-differential
      mobility analysis provides a quantitative, statistical analysis of mobility
      diameter, dynamic shape factor, polydispersity, and colloidal stability.

PMID- 29637987
TI  - Cooperative inter- and intra-layer lattice dynamics of photoexcited multi-walled
      carbon nanotubes studied by ultrafast electron diffraction.
AB  - Optical tuning and probing ultrafast structural response of nanomaterials driven
      by electronic excitation constitute a challenging but promising approach for
      understanding microscopic mechanisms and applications in microelectromechanical
      systems and optoelectrical devices. Here we use pulsed electron diffraction in a
      transmission electron microscope to investigate laser-induced tubular lattice
      dynamics of multi-walled carbon nanotubes (MWCNTs) with varying laser fluence and
      initial specimen temperature. Our photoexcitation experiments demonstrate
      cooperative and inverse collective atomic motions in intralayer and interlayer
      directions, whose strengths and rates depend on pump fluence. The electron-driven
      and thermally driven structural responses with opposite amplitudes cause a
      crossover between intralayer and interlayer directions. Our ab initio
      calculations support these findings and reveal that electrons excited from pi to
      pi* orbitals in a carbon tube weaken the intralayer bonds while strengthening the
      interlayer bonds along the radial direction. Moreover, by probing the structural
      dynamics of MWCNTs at initial temperatures of 300 and 100 K, we uncover the
      concomitance of thermal and nonthermal dynamical processes and their mutual
      influence in MWCNTs. Our results illustrate the nature of electron-driven
      nonthermal process and electron-phonon thermalization in the MWCNTs, and bear
      implications for the intricate energy conversion and transfer in materials at the
      nanoscale.

PMID- 29637988
TI  - Impact of anaemia on outcome in burn patients.
AB  - BACKGROUND: Currently, most critical care physicians maintain a patient's
      haemoglobin levels at 7 to 8 g dL-1. However, little data have been available on
      haemoglobin-related outcomes in burn patients. The purpose of this study was to
      evaluate inpatients with greater than 20% total body surface area burns and the
      effects of haemoglobin below 8 g dL-1 on clinical outcomes. METHODS: This study
      included 70 patients with burns amounting to greater than 20% of total body
      surface area. Data were retrospectively evaluated and included age, gender, adult
      respiratory distress syndrome presence, length of intensive care unit stay,
      length of mechanical ventilation, days requiring vasopressors, renal
      insufficiency, positive cultures/infections, cardiovascular complications, number
      of operations, inhalation injury, and mortality. Logistic regression analyses
      that were adjusted for age, sex, and percent total body surface area were used to
      assess the relationships between haemoglobin and multiple clinical outcomes. Odds
      ratios (OR) were estimated with 99% confidence intervals (99% CI). RESULTS:
      Haemoglobin below 8 g dL-1 was associated with a need for vasopressors (OR =
      2.17; 99% CI = 1.03-8.22). Furthermore, haemoglobin below 8 g dL-1 was associated
      with higher positive wound (OR = 2.86; 99% CI = 1.00-34.40), urine (OR = 4.63;
      99% CI = 1.15-67.00), and lung cultures (OR = 2.24; 99% CI = 1.06-5.47). These
      associations largely remained after controlling for blood transfusions.
      CONCLUSIONS: Contrary to most other patient groups, burn patients with burns
      amounting to greater than 20% of total body surface area and low haemoglobin
      levels were more likely to develop positive cultures in urine, wounds, and the
      lung and require vasopressor treatment.

PMID- 29637989
TI  - The impact of the blood glucose levels of non-diabetic critically ill patients on
      their clinical outcome.
AB  - BACKGROUND: Stress hyperglycaemia is thought to result from a hormonal response
      (release of catecholamines, glucocorticoids, glucagon, etc.) following stress,
      sepsis or trauma. Although stress hyperglycaemia is a very common finding in
      critically ill populations, there are many non-diabetic critically ill patients
      who do not develop a hyperglycaemic stress response to trauma or acute illness.
      We suggest that the lack of a hyperglycaemic stress response during the acute
      phase of a critical illness may correlate significantly with the clinical outcome
      of these critically ill non-diabetic patients. METHODS: This was a retrospective
      study of 700 non-diabetic critically ill patients admitted to the general
      intensive care unit (ICU) at Soroka Medical Center, Beer Sheva, Israel. We
      analyzed the clinical impact of the blood glucose levels of these patients
      measured during their first week of ICU hospitalization on their clinical
      outcome. RESULTS: Age, male gender, and the Acute Physiology and Chronic Health
      Evaluation (APACHE) score were found to be independent risk factors for new
      episodes of infection during the patients' stay in the ICU. Age and the APACHE
      and Sequential Organ Failure Assessment scores were found to be independent risk
      factors for intra-ICU mortality. In contrast, blood glucose analysis performed
      during the patients' stay in the ICU was not found to be an independent predictor
      for new infectious events or for mortality during the ICU stay. CONCLUSION: Our
      study did not demonstrate an association between blood glucose levels and
      clinical outcomes in non-diabetic critically ill patients.

PMID- 29637990
TI  - Day and time of admissions to intensive care units - does it matter?
AB  - BACKGROUND: The literature data pertaining to the significance of day and time of
      ICU admission for outcomes of patients are inconsistent. The issue has not been
      analysed in Poland to date. The aim of the study was to gather information about
      differences between patients admitted to ICU outside regular working hours (off
      hours) and those admitted during working hours (on-hours). METHODS: Analysis
      involved 20,651 patients from the Silesian Registry of Intensive Care Units
      carried out since 2010. The findings demonstrated that 34.8% of patients were
      admitted to ICUs during on-hours (between 8.00 a.m. and 3 p.m. on weekdays) and
      65.2% were admitted during off-hours (outside regular working hours). The
      incidence of admissions and data of patients in both groups were compared in
      terms of the population characteristics and treatment outcomes. RESULTS: The
      incidence of admissions (calculated per each 24 hours of treatment) was found to
      be almost twice as high during on-hours, as compared to off-hours (14.5 vs. 6.9
      patients/day). Patients admitted to the ICU during on-hours were less likely to
      be admitted from the surgical department (19.1% vs. 31.0%, P < 0.001), and more
      likely to be admitted from the emergency department (25.3% vs. 14.2%, P < 0.001).
      The incidence of off-hours admissions of cancer patients was lower (5.3% vs.
      10.8%, P < 0.001), as compared with patients with alcohol dependence syndrome
      (10.3% vs. 6.9%, P < 0.001). Patients admitted during off-hours were in more
      severe conditions and had higher APACHE II scores (on average, 23.8 +/- 8.8 vs.
      21.8 +/- 8.8, P < 0.001); their mortality rates were higher compared to the
      remaining population (46.8% vs. 39.4%, P < 0.001). CONCLUSIONS: Patients admitted
      to ICUs during off-hours are in more severe general condition and their treatment
      outcomes are worse, as compared to patients admitted to ICU during on-hours.

PMID- 29637991
TI  - Autoimmune anti-N-methyl-D-aspartate receptor encephalitis - the current state of
      knowledge based on a clinical case.
AB  - The aim of this article is to conduct an overview of the current state of
      knowledge about patients presenting anti-Nmethyl- D-aspartate receptor
      encephalitis associated with neoplastic process, as well as diagnosis and
      treatment. This disease concerns mainly young women and correlates with ovarian
      teratoma. Most important problems seems to be the difficulties in making a proper
      diagnosis ensuing from the rarity of this syndrome, the period from the
      appearance the first symptoms to starting treatment and the correct handling of
      intensive care complications. There are only a few articles describing severe,
      complicated cases of this type of encephalitis, requiring treatment in an
      intensive care unit.

PMID- 29637992
TI  - Factors influencing clinician's coherence with local antimicrobial guidelines in
      the management of sepsis.

PMID- 29637993
TI  - Always check anaesthetic equipment.

PMID- 29637994
TI  - Tips and troubleshooting during intubation with AirTraq videolaryngoscope.

PMID- 29637995
TI  - High serum procalcitonin concentration and dynamics of its changes as a
      prognostic factor of mortality.

PMID- 29637996
TI  - Heavily pigmented fibroepithelioma of Pinkus mimicking melanoma.

PMID- 29637997
TI  - Synergistic selection regimens drive the evolution of display complexity in birds
      of paradise.
AB  - Integrated visual displays that combine gesture with colour are nearly ubiquitous
      in the animal world, where they are shaped by sexual selection for their role in
      courtship and competition. However, few studies assess how multiple selection
      regimens operate on different components of these complex phenotypes on a
      macroevolutionary scale. Here, we study this issue by assessing how both sexual
      and ecological selection work together to influence visual display complexity in
      the birds of paradise. We first find that sexual dichromatism is highest in
      lekking species, which undergo more intense sexual selection by female choice,
      than non-lekking species. At the same time, species in which males directly
      compete with one another at communal display courts have more carotenoid-based
      ornaments and fewer melanin ornaments. Meanwhile, display habitat influences
      gestural complexity. Species that dance in the cluttered understorey have more
      complex dances than canopy-displaying species. Taken together, our results
      illustrate how distinct selection regimens each operate on individual elements
      comprising a complex display. This supports a modular model of display evolution,
      wherein the ultimate integrated display is the product of synergy between
      multiple factors that select for different types of phenotypic complexity.

PMID- 29637998
TI  - Retinal nerve fibre layer thinning is associated with worse visual outcome after
      optic neuritis in children with a relapsing demyelinating syndrome.
AB  - AIM: Optic neuritis may be monophasic or occur as part of a relapsing
      demyelinating syndrome (RDS), such as multiple sclerosis, aquaporin-4 antibody
      (AQP4-Ab) neuromyelitis optical spectrum disorder (NMOSD), or myelin
      oligodendrocyte glycoprotein antibody (MOG-Ab)-associated disease. The aims of
      this study were to test whether clinical, electrophysiological, and
      microstructural parameters differ in multiple-sclerosis-associated optic neuritis
      (MS-ON) and antibody-associated optic neuritis (Ab-ON); to identify the clinical
      and paraclinical characteristics of children suffering worse long-term visual
      outcome of RDS-optic neuritis; and to explore the relationship between RNFL
      thickness and clinical parameters in RDS-optic neuritis. METHOD: Forty-two
      children with optic neuritis were retrospectively studied: 22 with multiple
      sclerosis (MS-ON) and 20 with antibody-associated demyelination (Ab-ON: MOG-Ab=16
      and AQP4-Ab=4). Clinical and paraclinical features were analysed. RESULTS:
      Complete recovery of visual acuity was reported in 25 out of 42 children; eight
      out of 38 (21%) suffered moderate or severe visual impairment (logarithm of the
      minimum angle of resolution [logMAR]>0.5) in their worse eye, including four out
      of 38 who were blind (logMAR>1.3) in their worse eye (two with multiple
      sclerosis, two with AQP4-Ab NMOSD). None of the children with MOG-Ab were blind.
      Recurrence of optic neuritis was more common in the Ab-ON group than the MS-ON
      group (15 out of 20 vs seven out of 22, p=0.007). Retinal nerve fibre layer
      (RNFL) thickness at baseline inversely correlated with visual acuity at final
      follow-up (r=-0.41, p=0.008). There was no significant relationship between the
      number of episodes of optic neuritis and mean RNFL (r=-0.08, p=0.628), nor any
      significant relationship between the number of episodes of optic neuritis and
      visual impairment (r=0.03, p=0.794). INTERPRETATION: In children with RDS, long
      term visual impairment inversely correlated with RNFL thickness, but not with the
      number of relapses of optic neuritis. Optical coherence tomography may have a
      role in assessing children with optic neuritis to monitor disease activity and
      inform treatment decisions. WHAT THIS PAPER ADDS: Long-term visual impairment is
      reported in 40% of children with a relapsing demyelinating syndrome following
      optic neuritis. Relapse of optic neuritis, occurring more frequently in the non
      multiple-sclerosis group. Retinal nerve fibre layer thinning is associated with
      worse visual outcome. Optical coherence tomography can be used alongside clinical
      parameters as an objective measure of neuroretinal loss.

PMID- 29638000
TI  - Concentric targetoid scaly plaques in a patient with severe rheumatoid arthritis.

PMID- 29638001
TI  - A child's day: trends in time use in the UK from 1975 to 2015.
AB  - This paper examines change in school-age children's (8-16 years) time use in the
      United Kingdom between 1975 and 2015. Over this period, concerns for children's
      safety, technological change, and increased emphasis on success in school are
      widely argued to have altered children's daily lives, leading for example to less
      time outdoors, more time in screen-based activities, and more time focused on
      education. Using data from three national time use surveys collected in 1974-5,
      2000-01 and 2014-15, this paper explores the extent to which these arguments
      reflect actual change in how children spend their time throughout the day. The
      results show that between 1975 and 2015 children increased their time at home,
      and spent more time in screen-based activities and doing homework. Decreases in
      time in out-of-home activities were concentrated in time in unstructured play,
      partially offset by increased time in sport. A decomposition of trends revealed
      that, despite a narrowing of the gender gap in time in housework, gender remains
      a significant factor determining many aspects of children's time use. In
      contrast, the significance of age declined in most leisure activities, with the
      exception of screen-based activities where significant age differences emerged in
      2000 and widened further in 2015.

PMID- 29638002
TI  - Beyond the heartlands: deindustrialization, naturalization and the meaning of an
      'industrial' tradition.
AB  - Deindustrialization is a complex and multifaceted series of processes and
      transitions, reflecting the equally complicated web of social relationships and
      interdependencies that constitute(d) an industrial society. Contemporary scholars
      have looked beyond just the economic impact of industrial loss, to the cultural,
      temporal and spatial legacies and impacts wrought by the mass closures of the
      1980s, as well as the continuing presence of an industrial identity in struggles
      over representation and regeneration. However, deindustrialization has a history
      that precedes the volatility and culmination of that period, and has impacted
      upon a more geographically diverse range of former industrial locations than are
      commonly represented. The narratives that surround some sites are complicated by
      their displacement in time, place and discourse; they lack the political capital
      of an 'industrial' identity through this disassociation. In this article I aim to
      go beyond what we might consider the industrial 'heartlands' of the UK to a place
      that has felt the impact of deindustrialization, but which falls outside of the
      usual representations of the UK's industrial past. I explore how the industrial
      identity and memory of a place can be naturalized and selectively reworked for
      the needs of the hour, the very meaning of 'industrial' altered in the process. I
      argue that for sites unable to access or utilize the imagery of modern, heavy
      industry for community or promotional aims, deindustrialization becomes a process
      of rewriting an historic identity - one that sheds new light on industrial loss
      in diverse situations, and at an ever-increasing distance from closure.

PMID- 29638003
TI  - An ascending visual pathway to the dorsal telencephalon through the optic tectum
      and nucleus prethalamicus in the yellowfin goby Acanthogobius flavimanus
      (Temminck & Schlegel, 1845).
AB  - Dual visual pathways reaching the telencephalon appear to be an ancient
      vertebrate trait, but some teleost fish seem to possess only one pathway via the
      optic tectum. We undertook the present study to determine if and when this loss
      occurred during evolution. Tracer injection experiments to the optic nerve, the
      optic tectum, and the dorsal telencephalon were performed in the present study,
      to investigate ascending visual pathways to the dorsal telencephalon in an
      acanthopterygian teleost, the yellowfin goby Acanthogobius flavimanus (Temminck &
      Schlegel, 1845). We confirmed the presence of a nucleus prethalamicus (PTh) in
      the goby, which has been convincingly identified only in holocentrids, suggesting
      that this nucleus is present in other acanthopterygians. We found that the optic
      tectum projects to the PTh bilaterally. The PTh projects in turn to the dorsal
      telencephalon, ipsilaterally. These results suggest that the yellowfin goby
      possesses only an extrageniculate-like pathway, while a geniculate-like pathway
      could not be identified. This situation is common with that of holocentrids and
      may be a character common in acanthopterygians. It is possible that a geniculate
      like system was lost in the common ancestor of acanthopterygians, although the
      scenario for the evolution of ascending visual systems in actinopterygians
      remains uncertain due to the lack of precise knowledge in a number of
      actinopterygian taxons.

PMID- 29638004
TI  - Gray-bluish cutaneous pigmentation and ice-pick scars induced by vandetanib
      therapy.

PMID- 29637999
TI  - Impacts of microbiome metabolites on immune regulation and autoimmunity.
AB  - A vast number of studies have demonstrated a remarkable role for the gut
      microbiota and their metabolites in the pathogenesis of inflammatory diseases,
      including multiple sclerosis (MS). Recent studies in experimental autoimmune
      encephalomyelitis, an animal model of MS, have revealed that modifying certain
      intestinal bacterial populations may influence immune cell priming in the
      periphery, resulting in dysregulation of immune responses and neuroinflammatory
      processes in the central nervous system (CNS). Conversely, some commensal
      bacteria and their antigenic products can protect against inflammation within the
      CNS. Specific components of the gut microbiome have been implicated in the
      production of pro-inflammatory cytokines and subsequent generation of Th17 cells.
      Similarly, commensal bacteria and their metabolites can also promote the
      generation of regulatory T-cells (Treg), contributing to immune suppression.
      Short-chain fatty acids may induce Treg either by G-protein-coupled receptors or
      inhibition of histone deacetylases. Tryptophan metabolites may suppress
      inflammatory responses by acting on the aryl hydrocarbon receptor in T-cells or
      astrocytes. Interestingly, secretion of these metabolites can be impaired by
      excess consumption of dietary components, such as long-chain fatty acids or salt,
      indicating that the diet represents an environmental factor affecting the complex
      crosstalk between the gut microbiota and the immune system. This review discusses
      new aspects of host-microbiota interaction and the immune system with a special
      focus on MS as a prototype T-cell-mediated autoimmune disease of the CNS.

PMID- 29638005
TI  - Cancer mortality update with an exposure response analysis among styrene-exposed
      workers in the reinforced plastics boatbuilding industry.
AB  - BACKGROUND: There is sparse and inconsistent evidence of an association between
      styrene exposure and cancer. METHODS: This study examines mortality patterns in a
      previously studied cohort of 5201 workers employed in two Washington boat
      building facilities, extending follow-up 5 years. Standardized mortality ratios
      (SMR) were calculated using state rates as referent. Cox regression calculated
      rate ratios (RR) per year employed in styrene-exposed exposed jobs. RESULTS: No
      excess deaths from lymphohematopoietic cancers (LHCs) were observed (SMR: 0.99,
      95%CI: 0.74-1.30) when compared to the referent population; however, the relative
      risk increased with duration of employment in internal analyses. Conversely, lung
      cancer mortality was significantly elevated (SMR: 1.24, 95%CI: 1.08-1.41), but
      there was no evidence of a dose-response relationship. CONCLUSION: We found
      evidence that occupational exposure to styrene was associated with increased LHC
      risk, while no such association was observed for lung cancer.

PMID- 29638006
TI  - Effect of homogeneous static magnetic treatment on the adsorption capacity in
      maize seeds (Zea mays L.).
AB  - In order to analyze the treatment of seeds with homogeneous static magnetic field
      on the water adsorption process, an experimental-theoretical study of hygroscopic
      equilibrium in maize seeds (Zea mays L. cv. ICAV305) was carried out. Four
      treatments with magnetic induction of 80.0, 120.0, 160.0, and 200.0 mT were
      applied for 10 min, and there was a control group without treatment. The doses
      were selected because they showed a decrease in mean germination time. Treated
      seeds were subjected to an environment with a stable temperature of 30.0  degrees
      C +/- 0.1  degrees C and atmospheres of different relative humidity (h), using
      eight salt solutions saturated with water activity between 0.216 and 0.970.
      Curves were adjusted using the D'Arcy-Watt and modified Oswin models. It was
      found that the magnetic treatment of seeds affects adsorption, and the 200 mT-10
      min one was the most significant in affecting the mechanisms of adsorption of
      water, and increasing the number of adsorption sites connected to weak binds with
      D'Arcy-Watt's adjustment. Using the Oswin model for simulation, we verified that
      the magnetic stimulus affected the enthalpy of adsorption and the mechanism of
      incorporation of water vapor molecules to the structure of seminal cover. These
      results show that the magnetic pre-treatment of seeds has an effect on a seed's
      specific biophysical and physiological processes in the early stages of
      germination. Bioelectromagnetics. 39:343-351, 2018. (c) 2018 Wiley Periodicals,
      Inc.

PMID- 29638007
TI  - General and oral health problems among adults with focus on dentally anxious
      individuals.
AB  - OBJECTIVES: The objective of this epidemiological survey was to analyse the
      association between dental anxiety and health-related quality of life (HRQL)
      among adults. METHODS: Individuals were randomly selected (n = 3500), and they
      were interviewed by telephone and asked to complete a questionnaire concerning
      dental anxiety, HRQL [Oral Health Impact Profile-5 (OHIP-5) and EuroQol-5D (EQ
      5D)] and several socioeconomic variables. RESULTS: Dental anxiety was revealed as
      a significant factor relative to the OHIP-5 and EQ-5D. Dental anxiety had a
      stronger association with the OHIP-5 [odds ratio (OR): 3.50] than with the EQ-5D
      (OR: 1.75). In addition, socioeconomic status demonstrated a gradient, with
      higher ORs the lower the income and the likelihood of reporting poor HRQL.
      CONCLUSION: High dental anxiety was associated with lower HRQL.

PMID- 29638008
TI  - Automated video-based detection of nocturnal convulsive seizures in a residential
      care setting.
AB  - People with epilepsy need assistance and are at risk of sudden death when having
      convulsive seizures (CS). Automated real-time seizure detection systems can help
      alert caregivers, but wearable sensors are not always tolerated. We determined
      algorithm settings and investigated detection performance of a video algorithm to
      detect CS in a residential care setting. The algorithm calculates power in the 2
      6 Hz range relative to 0.5-12.5 Hz range in group velocity signals derived from
      video-sequence optical flow. A detection threshold was found using a training set
      consisting of video-electroencephalogaphy (EEG) recordings of 72 CS. A test set
      consisting of 24 full nights of 12 new subjects in residential care and
      additional recordings of 50 CS selected randomly was used to estimate
      performance. All data were analyzed retrospectively. The start and end of CS
      (generalized clonic and tonic-clonic seizures) and other seizures considered
      desirable to detect (long generalized tonic, hyperkinetic, and other major
      seizures) were annotated. The detection threshold was set to the value that
      obtained 97% sensitivity in the training set. Sensitivity, latency, and false
      detection rate (FDR) per night were calculated in the test set. A seizure was
      detected when the algorithm output exceeded the threshold continuously for 2
      seconds. With the detection threshold determined in the training set, all CS were
      detected in the test set (100% sensitivity). Latency was <=10 seconds in 78% of
      detections. Three/five hyperkinetic and 6/9 other major seizures were detected.
      Median FDR was 0.78 per night and no false detections occurred in 9/24 nights.
      Our algorithm could improve safety unobtrusively by automated real-time detection
      of CS in video registrations, with an acceptable latency and FDR. The algorithm
      can also detect some other motor seizures requiring assistance.

PMID- 29638009
TI  - Care Like Kin: Community Based Youth Serving Organizations and the Social
      Reproduction of Disconnected Youth in Rural America.
AB  - Increasing economic insecurity faced by older youth in rural America presents a
      crisis of social reproduction for disconnected youth in these areas. Increasingly
      community based youth serving organizations (CBYSOs) are recognizing and
      responding to the social reproduction needs of this particularly vulnerable youth
      population. Such responses are often hidden from funders, government agencies,
      and community residents. Yet these institutions play an important substitution
      function for disconnected youth and provide critical social support and social
      leverage for this population. Based on case studies of three CBYSOs in the San
      Joaquin Valley of California, this article explores how and why CBYSOs play a
      substitution function for disconnected youth in rural communities. It is the
      argument of this article that the social reproduction work of CBYSOs is
      undertaken with a ethic of care that may have the capacity to transform the
      political, social, and economic contexts that face this marginalized youth
      population.

PMID- 29638010
TI  - Ultrahigh-Performance Self-Powered Flexible Double-Twisted Fibrous Broadband
      Perovskite Photodetector.
AB  - Self-powered flexible photodetectors without an external power source can meet
      the demands of next-generation portable and wearable nanodevices; however, the
      performance is far from satisfactory becuase of the limited match of flexible
      substrates and light-sensitive materials with proper energy levels. Herein, a
      novel self-powered flexible fiber-shaped photodetector based on double-twisted
      perovskite-TiO2 -carbon fiber and CuO-Cu2 O-Cu wire is designed and fabricated.
      The device shows an ultrahigh detectivity of 2.15 * 1013 Jones under the
      illumination of 800 nm light at zero bias. CuO-Cu2 O electron block bilayer
      extends response range of perovskite from 850 to 1050 nm and suppresses dark
      current down to 10-11 A. The fast response speed of less than 200 ms is nearly
      invariable after dozens of cycles of bending at the extremely 90 bending angle,
      demonstrating excellent flexibility and bending stability. These parameters are
      comparable and even better than reported flexible and even rigid photodetectors.
      The present results suggest a promising strategy to design photodetectors with
      integrated function of self-power, flexibility, and broadband response.

PMID- 29638011
TI  - Effects of vitamin E and selenium supplementation on blood lipid peroxidation and
      cortisol concentration in dairy cows undergoing omentopexy.
AB  - Twenty dairy cows with left abomasal displacement were used to investigate the
      effects of vitamin E and selenium treatment on thiobarbituric acid reactive
      substances (TBARS) and blood cortisol in dairy cows stressed by omentopexy. The
      cows were randomly divided into two groups. Ten hours before surgery 6 g of DL
      alpha-tocopheryl acetate (6 mg/kg) and 67 mg of natrium selenite (0.1 mg/kg) in
      volume of 40 ml (Vitaselen(r) ) were administered subcutaneously to 10 cows; the
      control animals (n = 10) received an equivalent volume of injectable water (40
      ml). The injection of vitamin E and selenium produced a rapid rise (p < .05) in
      blood alpha-tocopherol and selenium concentrations. The serum vitamin E increased
      several times 10 hr after vitamin E and Se injection and raised continuously to
      the highest average concentration 21.6 mg/L at hr 24 after the surgery. The
      highest selenium concentration was seen 10 hr after selenium administration with
      holding the increased concentrations in comparison with initial ones during the
      whole study. Two-way ANOVA did not show significant treatment effect on plasma
      concentrations TBARS in the study. The plasma concentrations of thiobarbituric
      acid reactive substances reached the maximum value of 0.18 MUmol/L in the control
      group 5 hr after the surgery. Twenty-four hours after the surgery, the TBARS
      values returned to the initial ones. Serum cortisol increased in both groups
      after surgery. The highest cortisol concentrations were reached at 1 hr after
      surgery in the experimental and control group (56.7 +/- 28.8 and 65.3 +/- 26.1
      MUg/L respectively). A return to the levels similar to the initial ones was
      recognized 24 hr after the surgery. The ANOVA revealed a significant effect of
      vitamin E and selenium injection on plasma cortisol (p < .05). In conclusion, we
      have demonstrated that abdominal surgery resulted in typical stress changes with
      no significant effects of a single vitamin E/Se injection on blood lipid
      peroxidation. In addition, a weaker cortisol response to the abdominal surgery
      was recognized in animals treated with vitamin E and selenium.

PMID- 29638013
TI  - Perovskite-Initiated Photopolymerization for Singly Dispersed Luminescent
      Nanocomposites.
AB  - Metal halide perovskites have demonstrated rich photophysics and remarkable
      potential in photovoltaic and electroluminescent devices. However, the
      photoactivity of perovskite semiconductors in chemical processes remains
      relatively unexplored. Here, a general approach toward the synthesis of
      luminescent perovskite-polymer nanocomposites is reported, whereby perovskite
      nanocrystals are used as photoinitiators in the polymerization of vinyl monomers.
      The white-light illumination of a perovskite-monomer mixture triggers a free
      radical chain-growth polymerization process, giving rise to high molecular weight
      polymers of ~200 kDa. The in situ growth of polymer chains from the perovskite
      crystal surface allows the formation of individually dispersed nanocrystal cores
      within an encapsulating polymer matrix, and leads to a significant threefold
      enhancement in photoluminescence quantum yield. This photoluminescence
      enhancement is attributed to the spatial separation of the perovskite
      nanocrystals and hence the deactivation of energy transfer to dark crystals. The
      resulting perovskite-polymer nanocomposites exhibit excellent stability against
      moisture and are shown to be useful as functional downconversion phosphor films
      for luminescent displays and lighting.

PMID- 29638012
TI  - Evaluation of a new biphasic calcium phosphate for maxillary sinus floor
      elevation: Micro-CT and histomorphometrical analyses.
AB  - OBJECTIVES: Synthetic biphasic calcium phosphate (BCP) with a hydroxyapatite/beta
      tricalcium phosphate (HA/beta-TCP) ratio of 60/40 (BCP60/40) is successfully used
      as alternative for autologous bone in patients undergoing maxillary sinus floor
      elevation (MSFE) for dental implant placement. A high percentage of HA in
      BCP60/40 may hamper efficient scaffold remodeling. Osteogenesis and
      neovascularization are pivotal in effective bone regeneration. We aimed to
      investigate whether differences exist in osteogenic and/or vasculogenic potential
      of BCP60/40 and BCP20/80 in patients undergoing MSFE. MATERIALS AND METHODS:
      Twenty patients undergoing MSFE were treated with BCP60/40 (n = 10) or BCP20/80
      (n = 10). Bone and graft volumes were determined by micro-computed tomography and
      histomorphometrical analysis of biopsies of the augmented region. Osteoid
      volumes, number of osteoclasts, and blood vessels were determined by
      histomorphometrical analysis. The biopsies were taken 6.5 months (26 weeks)
      postoperatively prior to dental implant placement. RESULTS: Bone and osteoid
      volumes were 9.7% and 0.8% higher at the most cranial side of the BCP20/80
      biopsies compared to the BCP60/40 biopsies. Graft volumes, number of osteoclasts,
      and blood vessels were similar in both groups. CONCLUSIONS: BCP20/80 showed
      enhanced osteogenic potential in patients undergoing MSFE compared to BCP60/40,
      due to either a faster bone remodeling rate or an earlier start of bone formation
      in BCP20/80-treated patients, suggesting that a higher TCP content positively
      contributes to the bone remodeling rate. Therefore, BCP20/80 might perform
      better, at least in the short term, as a scaffold for bone augmentation in the
      MSFE model than BCP60/40 as more bone is formed, and more osteoid is deposited at
      the cranial side in BCP20/80-treated patients compared to BCP60/40-treated
      patients. However, catch-up of BCP60/40 in the long term cannot be ruled out.

PMID- 29638014
TI  - Effects of lactic acid bacteria and smectite after aflatoxin B1 challenge on the
      growth performance, nutrient digestibility and blood parameters of broilers.
AB  - This study aimed to investigate the effect of lactic acid bacteria (LAB) and
      smectite on the growth performance, nutrient digestibility and blood parameters
      of broilers that were fed diets contaminated with aflatoxin B1 (AFB1 ). A total
      of 480 newly hatched male Arbor Acres broilers were randomly allocated into four
      groups with six replicates of 20 chicks each. The broilers were fed diets with
      the AFB1 (40 MUg/kg) challenge or without (control) it and supplemented with
      smectite (3.0 g/kg) or LAB (4.0 * 1010  CFU/kg) based on the AFB1 diet. The trial
      lasted for 42 days. The results showed that during days 1-42 of AFB1 challenge,
      the feed intake (FI) and body weight gain (BWG) were depressed (p < .05). The
      inclusion of LAB and smectite increased (p < .05) the BWG by 71.58 and 41.89
      g/bird, respectively, which reached the level of the control diet (p >= .05), but
      there were no differences (p >= .05) in performance between LAB and smectite. LAB
      and smectite also increased (p < .05) the apparent total tract digestibility of
      the crude protein. Regarding the blood parameters, AFB1 decreased (p < .05) the
      levels of red blood cell count, haematocrit, mean corpuscular volume,
      haemoglobin, albumin and total protein. In the meantime, the AFB1 increased (p <
      .05) leucocyte counts, urea nitrogen, cholesterol, total bilirubin, creatinine,
      glutamic-pyruvic transaminase, glutamic oxaloacetic transaminase and alkaline
      phosphatase. By contrast, LAB and smectite affected (p < .05) these parameters in
      the opposite direction. It can be concluded that after the AFB1 challenge, LAB
      and smectite have similar effects on the growth and health of the broilers,
      suggesting that LAB could be an alternative against AFB1 in commercial animal
      feeds.

PMID- 29638015
TI  - Processing traits and digestibility of extruded dog foods with soy protein
      concentrate.
AB  - Soya bean protein concentrate (SPC) with two particle sizes were evaluated on
      extrusion parameters, kibble formation, digestibility and palatability of dog
      foods. Eight diets were extruded: PBM-control diet based on poultry by-product
      meal (PBM); GM-a diet in which corn gluten meal (GM) replaced 45% of the diet
      protein; cSPC15%, cSPC30% and cSPC45%-diets in which SPC of coarse particle size
      (600 MUm) replaced 15%, 30% and 45% of the diet protein; and sSPC15%, sSPC30% and
      sSPC45%-diets in which SPC of small particle size (200 MUm) replaced 15%, 30% and
      45% of the diet protein. The digestibility of nutrients was evaluated for the
      PBM, GM, cSPC45% and sSPC45% diets, using six dogs per food. The PBM, GM and
      cSPC45% diets were compared for palatability. Data were submitted for analysis of
      variance, and the means were compared by polynomial contrasts or Tukey's test (p
      < .05). The cSPC increased the specific mechanical energy (SME) application,
      extrusion temperature and pressure linearly, resulting in lower kibble density
      and higher expansion and starch gelatinization (SG) (p < .01). When comparing the
      PBM, GM, cSPC45% and sSPC45% diets, higher SME, extrusion temperature and
      pressure, SG and kibble expansion were verified for the cSPC45% diet (p < .05).
      The DM, fat and crude protein digestibility were similar among diets. Faecal pH,
      ammonia and lactate did not differ, demonstrating that the removal of
      oligosaccharides and soluble non-starch polysaccharides of SPC produces an
      ingredient with mostly non-fermentable fibre. Dogs preferred the PBM to the GM
      diet (p < .05), but consumed the PBM and cSPC45% foods equally. In conclusion,
      SPC exhibited good extrusion functionality, favouring kibble expansion and SG,
      with high digestibility, similar to that of PBM. The removal of soluble compounds
      from soya beans resulted in an ingredient with low fermentable fibre content,
      which did not alter faecal formation or characteristics.

PMID- 29638016
TI  - Congenital aortic paravalvular tunnel masquerading as a recurrent ventricular
      septal defect.
AB  - A 4-year-old female underwent surgical repair of an unusual variation of an aorto
      left ventricular tunnel (ALVT). Serial echocardiograms had demonstrated previous
      spontaneous closure of a perimembranous ventricular septal defect (VSD). The
      patient presented with concern for residual VSD which was later demonstrated to
      be an eccentric jet through an ALVT. This case emphasizes early and accurate
      diagnosis for ALVTs and how they can be misdiagnosed as VSDs.

PMID- 29638017
TI  - Magnetoactive Acoustic Metamaterials.
AB  - Acoustic metamaterials with negative constitutive parameters (modulus and/or mass
      density) have shown great potential in diverse applications ranging from sonic
      cloaking, abnormal refraction and superlensing, to noise canceling. In
      conventional acoustic metamaterials, the negative constitutive parameters are
      engineered via tailored structures with fixed geometries; therefore, the
      relationships between constitutive parameters and acoustic frequencies are
      typically fixed to form a 2D phase space once the structures are fabricated.
      Here, by means of a model system of magnetoactive lattice structures, stimuli
      responsive acoustic metamaterials are demonstrated to be able to extend the 2D
      phase space to 3D through rapidly and repeatedly switching signs of constitutive
      parameters with remote magnetic fields. It is shown for the first time that
      effective modulus can be reversibly switched between positive and negative within
      controlled frequency regimes through lattice buckling modulated by theoretically
      predicted magnetic fields. The magnetically triggered negative-modulus and cavity
      induced negative density are integrated to achieve flexible switching between
      single-negative and double-negative. This strategy opens promising avenues for
      remote, rapid, and reversible modulation of acoustic transportation, refraction,
      imaging, and focusing in subwavelength regimes.

PMID- 29638018
TI  - Evolocumab and lipoprotein apheresis combination therapy may have synergic
      effects to reduce low-density lipoprotein cholesterol levels in heterozygous
      familial hypercholesterolemia: A case report.
AB  - A 49 years old woman (weight 68 kg, BMI 27.3 kg/m2 ) with heterozygous familial
      hypercholesterolemia (HeFH) and multiple statin intolerance with muscle aches and
      creatine kinase elevation, presented at the Outpatient Lipid Clinic of Verona
      University Hospital in May 2015. Hypercholesterolemia was firstly diagnosed
      during adolescence, followed in adulthood by a diagnosis of Cogan's syndrome, a
      rheumatologic disorder characterized by corneal and inner ear inflammation. No
      xanthomas, corneal arcus, or vascular bruits were detectable at physical
      examination. Screening for macrovascular complications did not reveal relevant
      damages. Ongoing medical therapy included salicylic acid, methylprednisolone,
      methotrexate, and protonic-pump inhibitor. In the absence of specific lipid
      lowering therapy, plasma lipid levels at first visit were: total-cholesterol =
      522 mg/dL, LDL-cholesterol = 434 mg/dL, HDL-cholesterol = 84 mg/dL, triglycerides
      = 120 mg/dL, Lp(a) = 13 mg/dL. On December 2015, evolocumab 140 mg sc every 2
      weeks was initiated. After a 24-week treatment, the LDL-cholesterol levels
      decreased by an average of 21.2% to 342 +/- 22 mg/dL (mean +/- SD). On May 2016,
      LDL-apheresis (H.E.L.P.system) was started as add-on therapy. Compared to the
      average levels obtained during the evolocumab monotherapy period, the LDL
      cholesterol was reduced by 49.4%, thus reaching an inter-apheresis level (mean +/
      SD) of 173 +/- 37 mg/dL. This report suggests that a combination therapy with
      evolocumab and lipoprotein-apheresis may have synergic effects on circulating
      lipid levels. Its relevance as a highly effective treatment option for
      hyperlipidemia in HeFH patients warrants further investigation in larger
      datasets.

PMID- 29638019
TI  - A Hepatocyte-Mimicking Antidote for Alcohol Intoxication.
AB  - Alcohol intoxication causes serious diseases, whereas current treatments are
      mostly supportive and unable to remove alcohol efficiently. Upon alcohol
      consumption, alcohol is sequentially oxidized to acetaldehyde and acetate by the
      endogenous alcohol dehydrogenase and aldehyde dehydrogenase, respectively.
      Inspired by the metabolism of alcohol, a hepatocyte-mimicking antidote for
      alcohol intoxication through the codelivery of the nanocapsules of alcohol
      oxidase (AOx), catalase (CAT), and aldehyde dehydrogenase (ALDH) to the liver,
      where AOx and CAT catalyze the oxidation of alcohol to acetaldehyde, while ALDH
      catalyzes the oxidation of acetaldehyde to acetate. Administered to alcohol
      intoxicated mice, the antidote rapidly accumulates in the liver and enables a
      significant reduction of the blood alcohol concentration. Moreover, blood
      acetaldehyde concentration is maintained at an extremely low level, significantly
      contributing to liver protection. Such an antidote, which can eliminate alcohol
      and acetaldehyde simultaneously, holds great promise for the treatment of alcohol
      intoxication and poisoning and can provide therapeutic benefits.

PMID- 29638021
TI  - Modified maxillary reconstruction technique for Brown's class III defects by
      subdividing a rhomboid shaped iliac crest into 2 subunits.
AB  - BACKGROUND: Men and women share a common maxillary morphology with heterogeneity
      in size. This indicated that our technique of reconstruction with a rhomboid
      shaped iliac crest bone flap incorporating a 30 degrees  vertical wedge osteotomy
      may be widely used for Brown's class III maxillectomy defect reconstruction among
      a population with class I skeletal profile. The reconstruction of Brown's class
      III maxillary defects is extremely challenging. The purpose of this study was to
      closely study the maxilla geometrically in order to establish a standardized
      maneuver, which facilitates conversion of the iliac bone flap into a natural
      maxilla's contours. METHODS: We evaluated the geometries of 40 adult maxillas.
      The perimeter lengths of perinasal and infraorbital subunits were analyzed, in
      addition to the intersecting angle (delta) of both subunits. Sex variation was
      evaluated using the Student's t test. RESULTS: In the 80 studied unilateral
      maxillas (40 maxillas from 18 men and 22 women), there were no significant sex
      differences for delta (P = .1527). In addition, both sexes shared common
      morphological features, hence, in surgical reconstruction, the delta can be
      constantly set at 150 degrees . Perimeter of bone segments had a greater
      intersubject variability (coefficient of variation [CV] of approximately 4.5-11).
      From both cadaveric dissections and clinical applications, our results have shown
      that our standard maneuver was reproducible and reliable in reestablishing
      natural facial contours. CONCLUSION: Our standard maneuver can serve as a
      universal guideline, with individualized perimeter manipulations, to yield an
      aesthetically natural and functional outcome.

PMID- 29638020
TI  - Noninvasive prediction of portal pressure with MR elastography and DCE-MRI of the
      liver and spleen: Preliminary results.
AB  - BACKGROUND: Portal hypertension (PH), defined by hepatic venous pressure gradient
      (HVPG) >=5 mmHg and clinically significant PH, defined by HVPG >=10 mmHg, are
      complications of chronic liver disease. PURPOSE: To assess the diagnostic
      performance of MR elastography (MRE) and dynamic contrast-enhanced MRI (DCE-MRI)
      of the liver and spleen for the prediction of PH and clinically significant PH,
      in comparison with a qualitative PH imaging scoring system. STUDY TYPE: IRB
      approved prospective study. POPULATION: In all, 34 patients with chronic liver
      disease who underwent HVPG measurement. FIELD STRENGTH/SEQUENCE: 1.5/3T
      examination including 2D-GRE MRE (n = 33) and DCE-MRI of the liver/spleen (n =
      28). ASSESSMENT: Liver and spleen stiffness were calculated from elastogram maps.
      DCE-MRI was analyzed using model-free parameters and pharmacokinetic modeling.
      Two observers calculated qualitative PH imaging scores based on routine images.
      STATISTICAL TESTS: Imaging parameters were correlated with HVPG. Receiver
      operating characteristic (ROC) analysis was performed for prediction of PH and
      clinically significant PH. RESULTS: There were significant correlations between
      DCE-MRI parameters (liver time-to-peak, r = 0.517 / P = 0.006, liver distribution
      volume, r = 0.494 / P = 0.009, liver upslope, r = -0.567 / P = 0.002), liver
      stiffness (r = 0.478 / P = 0.016), PH imaging score (r = 0.441 / P = 0.009), and
      HVPG. ROC analysis provided significant area under the ROC (AUROCs) for PH (liver
      upslope 0.765, liver stiffness 0.809, spleen volume/diameter 0.746-0.731, PH
      imaging score 0.756) and for clinically significant PH (liver and spleen
      perfusion parameters 0.733-0.776, liver stiffness 0.742, PH imaging score 0.742).
      The ratio of liver stiffness to liver upslope had the highest AUROC for
      diagnosing PH (0.903) and clinically significant PH (0.785). DATA CONCLUSION:
      These preliminary results suggest that the combination of liver stiffness and
      perfusion metrics provide excellent accuracy for diagnosing PH, and fair accuracy
      for clinically significant PH. Combined MRE and DCE-MRI outperformed qualitative
      imaging scores for prediction of PH. LEVEL OF EVIDENCE: 1 Technical Efficacy:
      Stage 2 J. Magn. Reson. Imaging 2018;48:1091-1103.

PMID- 29638022
TI  - Cytopathology of non-invasive follicular thyroid neoplasm with papillary-like
      nuclear features: A comparative study with similar patterned papillary thyroid
      carcinoma variants.
AB  - OBJECTIVE: Noninvasive follicular thyroid neoplasm with papillary-like nuclear
      features (NIFTP) is a recently described, indolent thyroid tumor, with well
      defined histopathological diagnostic criteria. Cytology features are not well
      documented. We reviewed cytology of histologically proven cases of NIFTP and some
      of its common differentials to look for salient diagnostic features. METHODS:
      Cases reported on histopathology as follicular variant of papillary thyroid
      carcinoma (FVPTC), or NIFTP between July 2015 and April 2017 having available
      cytology smears were retrieved and reclassified as NIFTP, FVPTC, and classical
      papillary thyroid carcinoma with predominant follicular pattern (PTC-FP).
      Cytological features were assessed, classified as per The Bethesda System for
      Reporting Cytopathology and compared. RESULTS: There were 23 NIFTP cases, 18
      FVPTC and 8 PTC-FP. A microfollicle-predominant pattern was seen in all. Nuclear
      score was 2 in most NIFTP cases (61%). Pseudoinclusions were absent. NIFTP showed
      features of atypia of undetermined significance/follicular lesion of undetermined
      significance (AUS/FLUS) (III) in 61%, follicular neoplasm/suspicious for a
      follicular neoplasm (FN/SFN) (IV) in 35% and suspicious for malignancy (SFM) (V)
      in 4%. Most of the FVPTCs were also called FN/SFN (IV) (56%) or AUS/FLUS (III)
      (22%). Nuclear features did not statistically differ from NIFTP. PTC-FP showed
      high-grade cytology in 75%, and higher nuclear score (3 in 75%) in contrast to
      NIFTP (P = .003). CONCLUSION: NIFTP and FVPTC show a similar distribution among
      the Bethesda categories hence precluding conclusive distinction on cytology. PTC
      FP, in contrast, was found to have a statistically significant higher nuclear
      score and more commonly showed malignant cytology.

PMID- 29638024
TI  - 4D flow MRI quantification of mitral and tricuspid regurgitation: Reproducibility
      and consistency relative to conventional MRI.
AB  - BACKGROUND: In patients with mitral or tricuspid valve regurgitation, evaluation
      of regurgitant severity is essential for determining the need for surgery. While
      transthoracic echocardiography is widely accessible, it has limited
      reproducibility for grading inlet valve regurgitation. Multiplanar cardiac MRI is
      the quantitative standard but requires specialized local expertise, and is thus
      not widely available. Volumetric 4D flow MRI has potential for quantitatively
      grading the severity of inlet valve regurgitation in adult patients. PURPOSE: To
      evaluate the accuracy and reproducibility of volumetric 4D flow MRI for
      quantification of inlet valvular regurgitation compared to conventional
      multiplanar MRI, which may simplify and improve accessibility of cardiac MRI.
      STUDY TYPE: This retrospective, HIPAA-compliant imaging-based comparison study
      was conducted at a single institution. SUBJECTS: Twenty-one patients who
      underwent concurrent multiplanar and 4D flow cardiac MRI between April 2015 and
      January 2017. FIELD STRENGTH/SEQUENCES: 3T; steady-state free-precession (SSFP),
      2D phase contrast (2D-PC), and postcontrast 4D flow. ASSESSMENT: We evaluated the
      intertechnique (4D flow vs. 2D-PC), intermethod (direct vs. indirect
      measurement), interobserver and intraobserver reproducibility of measurements of
      regurgitant flow volume (RFV), fraction (RF), and volume (RVol). STATISTICAL
      TESTS: Statistical analysis included Pearson correlation, Bland-Altman
      statistics, and intraclass correlation coefficients. RESULTS: There was high
      concordance between 4D flow and multiplanar MRI, whether using direct or indirect
      methods of quantifying regurgitation (r = 0.813-0.985). Direct interrogation of
      the regurgitant jet with 4D flow showed high intraobserver consistency (r = 0.976
      0.999) and interobserver consistency (r = 0.861-0.992), and correlated well with
      traditional indirect measurements obtained as the difference between stroke
      volume and forward outlet valve flow. DATA CONCLUSION: 4D flow MRI provides
      highly reproducible measurements of mitral and tricuspid regurgitant volume, and
      may be used in place of conventional multiplanar MRI. LEVEL OF EVIDENCE: 4
      Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;48:1147-1158.

PMID- 29638023
TI  - Association between serum uric acid, high sensitive C-reactive protein and pro
      oxidant-antioxidant balance in patients with metabolic syndrome.
AB  - There is persuasive evidence that oxidative stress and inflammation are features
      of the metabolic syndrome (MetS). We have investigated the relationship between
      serum pro-oxidant-antioxidant balance (PAB), serum uric acid, and high sensitive
      C-reactive protein (hs-CRP) in 7,208 participants from the MASHAD study cohort,
      who were categorized as having MetS, or not, using International Diabetes
      Foundation (IDF) criteria. Serum hs-CRP was measured by Polyethylene glycol (PEG)
      enhanced immunoturbidimetry method using an Alycon analyzer (ABBOTT, Chicago, IL,
      USA). A colorimetric method was used to determine serum PAB. Serum PAB values
      were significantly higher in the individuals with MetS compared to those without
      (P < 0.001). Furthermore, there was a step-wise increase in mean serum PAB
      concentrations as the number of components of the MetS increased. The combination
      of features of MetS had different association with serum PAB and hs-CRP. Multiple
      linear regression analysis showed that body mass index (BMI, B = 2.04, P <
      0.001), physical activity level (PAL, B = 18.728, P = 0.001), serum uric acid (B
      = -1.545, P = 0.003), and serum C-reactive protein (B = 0.663, P < 0.001) were
      associated with serum PAB in individuals with MetS. Multiple logistic regression
      analysis showed that serum PAB (B = 0.002, P < 0.001, CI = 1.001-1.003), serum C
      reactive protein (B = 0.007, P < 0.015, CI = 1.001-1.013), and serum uric acid (B
      = 0.207, P < 0.001, CI = 1.186-1.277) were all significantly associated with
      MetS. Serum PAB was strongly associated with serum uric acid and serum hs-CRP.
      Moreover, serum PAB as well as serum uric acid and serum hs-CRP were
      independently associated with MetS. Individual features of MetS were also
      associated with serum hs-CRP and PAB. (c) 2018 BioFactors, 44(3):263-271, 2018.

PMID- 29638026
TI  - Bioinspired Hydrogel Interferometer for Adaptive Coloration and Chemical Sensing.
AB  - Living organisms ubiquitously display colors that adapt to environmental changes,
      relying on the soft layer of cells or proteins. Adoption of soft materials into
      an artificial adaptive color system has promoted the development of material
      systems for environmental and health monitoring, anti-counterfeiting, and stealth
      technologies. Here, a hydrogel interferometer based on a single hydrogel thin
      film covalently bonded to a reflective substrate is reported as a simple and
      universal adaptive color platform. Similar to the cell or protein soft layer of
      color-changing animals, the soft hydrogel layer rapidly changes its thickness in
      response to external stimuli, resulting in instant color change. Such
      interference colors provide a visual and quantifiable means of revealing rich
      environmental metrics. Computational model is established and captures the key
      features of hydrogel stimuli-responsive swelling, which elucidates the mechanism
      and design principle for the broad-based platform. The single material-based
      platform has advantages of remarkable color uniformity, fast response, high
      robustness, and facile fabrication. Its versatility is demonstrated by diverse
      applications: a volatile-vapor sensor with highly accurate quantitative
      detection, a colorimetric sensor array for multianalyte recognition, breath
      controlled information encryption, and a colorimetric humidity indicator.
      Portable and easy-to-use sensing systems are demonstrated with smartphone-based
      colorimetric analysis.

PMID- 29638025
TI  - Molecular cloning and expression of FGF2 gene in pre-implantation developmental
      stages of in vitro-produced sheep embryos.
AB  - Early embryonic mortality is one of the main sources of reproductive loss in
      domestic ruminants including sheep. Fibroblast growth factor-2 (FGF-2) is a
      member of FGFs family that mediates trophoblast activities and regulates
      embryonic development in various species. In this study, we have cloned,
      characterized sheep FGF2 cDNA (KU316368) and studied the expression in sheep
      embryos. Ovaries of non-pregnant sheep were collected from local abattoir and
      matured in culture medium at 38.5oC, 5% CO2 , 95% humidity for 22-24 hr. The
      matured oocytes were inseminated with capacitated spermatozoa in Brackett and
      Oliphant medium and resulted embryos were cultured in CO2 incubator for 6-7 days
      to complete the developmental stages from two cells to blastocyst stage. Total
      RNA was extracted from immature oocytes (n = 100), mature oocytes (n = 100) and
      different stages of embryos such as 2 cell (n = 50), 4 cell (n = 25), 8 cell (n =
      12), 16 cell (n = 6), morula (n = 5) and blastocyst (n = 3). The total RNA
      isolated from the oocytes and embryos was reverse transcribed and subjected to
      real-time polymerase chain reaction using sequence-specific primers and SYBR
      green as the DNA dye. On sequence analysis, the nucleotide sequence of sheep FGF2
      exhibited highest sequence similarity with cattle (100%) and least with rat and
      mouse (69.2%). At the deduced amino acid level, a highest degree of similarity
      was noticed with cattle, buffalo, goat, pig, camel and horse (100%) and lowest
      degree of identity with rat, human and mouse (98.2%). The FGF2 mRNA expression
      was higher in immature and mature oocytes and gradually decreases from 2-cell
      stage of embryo to the blastocyst stage. More over a significant differences in
      FGF2 mRNA expression (p < .05) were observed between immature oocytes and all pre
      implantation stages of embryo. It can be concluded that FGF-2 plays a significant
      role in pre-implantation and early development of embryos in sheep.

PMID- 29638027
TI  - Oleic acid enhances keratinocytes differentiation via the upregulation of miR-203
      in human epidermal keratinocytes.
AB  - BACKGROUND: Oleic acid (OA) is an unsaturated free fatty acid (FFA) constituent
      of sebum. FFAs modulate keratinocyte differentiation. In this study, we
      determined whether OA affects keratinocyte differentiation in neonatal human
      epidermal keratinocytes (HEKn). METHODS: HEKn was grown in EpiLife medium. The
      cells were treated with various concentrations of OA. The expression levels of
      keratin 10 and involucrin were determined using Western blotting (for the
      proteins) and quantitative real time polymerase chain reaction (qRT-PCR) (for the
      mRNAs). Cytoskeletal changes were investigated by immunofluorescent staining. The
      levels of microRNA (miR)-203 were determined by stem-loop qRT-PCR. The effect of
      miR-203 on keratinocyte differentiation was evaluated using anti-miR-203.
      RESULTS: Treatment with OA promoted the expression of keratin 10 and involucrin,
      which are markers of spinous and granular layer keratinocytes, respectively.
      Treatment with OA also induced cell stratification and cytoskeletal changes such
      as the concentric ring organization of actin, a loss of planar polarity, and
      increased localization of epithelial cadherin (E-cadherin) at cell-cell contacts.
      OA increased the expression of miR-203, which is associated with keratinocyte
      differentiation, and reduced the expression of p63, a target of miR-203, in HEKn.
      Furthermore, transfection with anti-miR-203 suppressed the OA-induced expression
      of involucrin. CONCLUSIONS: Oleic acid accelerates keratinocyte differentiation
      via the upregulation of miR-203 in HEKn under sub-confluent conditions.

PMID- 29638028
TI  - Exercise interventions in healthy older adults with sarcopenia: A systematic
      review and meta-analysis.
AB  - OBJECTIVE: To systematically assess the effects of exercise interventions on body
      composition and functional outcomes in older adults with sarcopenia. METHODS:
      PubMed/Medline, Embase and Cochrane Library were searched from 2006 to 2017 for
      exercise randomised controlled trials and controlled clinical trials in adults 60
      years and older with sarcopenia. Preferred Reporting Items for Systematic Review
      and Meta-Analysis protocol (PRISMA-P) and Physiotherapy Evidence Database (PEDro)
      scale assessed internal validity. Meta-analysis and sensitivity analysis were
      performed. RESULTS: Searches retrieved 1512 titles. Thirty-two full texts were
      evaluated, and six trials were included. Methodological quality was 5.5 (0-10).
      Meta-analysis revealed that knee-extension strength (P <= 0.01), timed up and go
      (P < 0.0001), appendicular muscle mass (P = 0.04) and leg muscle mass (P = 0.04)
      significantly improved in response to exercise interventions. CONCLUSIONS:
      Exercise interventions significantly improved strength, balance and muscle mass.
      However, the number of trials was small and the training effect was inconsistent
      due to heterogeneity in exercise mode, duration and intensity. Lack of detailed
      description makes it impossible to reflect on the progressive resistance training
      approaches used. More research is needed to confirm these findings.

PMID- 29638029
TI  - Comparative thermographic analysis at pre- and postcryolipolysis treatment:
      Clinical case report.
AB  - INTRODUCTION: Although the exact cryolipolysis mechanisms on adipose tissue
      remain unknown, the current literature indicates that it may occur a
      crystallization followed by an ischemic reaction which generates an inflammatory
      process. OBJECTIVE: To evaluate thermographically, the tissue's circulatory
      pattern of a patient submitted to the cryolipolysis technique and the beginning
      of the inflammatory process, through variations of temperature gradients and the
      evaluation of the pains degree of the patient in these same moments. METHODS: A
      descriptive study, of an interventional case report, performed in an 18-year-old
      patient who had clearly visible fat in the lower abdomen area, with a skin fold
      greater than 2 centimeters and body mass index <= 30 kg/m2 . RESULTS: Comparing
      the maximum temperatures showed on the last thermography with the pre-application
      image, an increase of 0.4 degrees C was observed, which is suggestive of
      abnormality. Regarding the minimum temperatures verified, there was a
      significative decrease in the temperature with the procedure, which was observed
      on the last 5 minutes (DeltaT = 9.8 degrees C). However, in 48 hour, the minimum
      temperature began to recover (DeltaT = 0.3 degrees C). CONCLUSION: The observed
      data indicate that there was a significant decrease in the temperature during the
      cooling phase, whereas in the recovery phase, the inverse was found.

PMID- 29638030
TI  - Interfacial Passivation of the p-Doped Hole-Transporting Layer Using General
      Insulating Polymers for High-Performance Inverted Perovskite Solar Cells.
AB  - Organic-inorganic lead halide perovskite solar cells (PVSCs), as a competing
      technology with traditional inorganic solar cells, have now realized a high power
      conversion efficiency (PCE) of 22.1%. In PVSCs, interfacial carrier recombination
      is one of the dominant energy-loss mechanisms, which also results in the
      simultaneous loss of potential efficiency. In this work, for planar inverted
      PVSCs, the carrier recombination is dominated by the dopant concentration in the
      p-doped hole transport layers (HTLs), since the F4-TCNQ dopant induces more
      charge traps and electronic transmission channels, thus leading to a decrease in
      open-circuit voltages (VOC ). This issue is efficiently overcome by inserting a
      thin insulating polymer layer (poly(methyl methacrylate) or polystyrene) as a
      passivation layer with an appropriate thickness, which allows for increases in
      the VOC without significantly sacrificing the fill factor. It is believed that
      the passivation layer attributes to the passivation of interfacial recombination
      and the suppression of current leakage at the perovskite/HTL interface. By
      manipulating this interfacial passivation technique, a high PCE of 20.3% is
      achieved without hysteresis. Consequently, this versatile interfacial passivation
      methodology is highly useful for further improving the performance of planar
      inverted PVSCs.

PMID- 29638031
TI  - Overrated hedonic judgment of odors in patients with schizophrenia.
AB  - AIMS: The odor identification ability and its hedonic judgment in patients with
      schizophrenia were evaluated in the study. The association between olfactory
      performance and negative symptoms and beta-endorphin concentration was also
      analyzed. METHODS: Study groups consisted of 23 patients with negative symptoms
      (PN) and 25 without predominant negative symptoms (PP) and 21 healthy
      individuals. The University of Pennsylvania Smell Identification Test, odor
      hedonic evaluation, and plasma concentrations of beta-endorphin assay in all
      participants were performed. RESULTS: PN perceived the poorer olfactory
      identification; nevertheless, they evaluated unpleasant odors as more pleasant
      than PP and controls. Beta-endorphin concentration was significantly higher among
      PN than in other study groups. No association was observed between beta-endorphin
      and odors identification and odor hedonic judgment among all study groups.
      CONCLUSIONS: There is potential relationship between increased beta-endorphin
      concentration and severity of negative symptoms. Patients with predominant
      negative symptoms tend to evaluate odors as significantly more pleasant.
      Individuals with this subtype of schizophrenia might present specific, altered
      pattern of smell identification and hedonic judgment. Presumably, beta-endorphin
      has no direct influence on olfactory identification performance and hedonic
      judgment in schizophrenia.

PMID- 29638033
TI  - Commentary on Degenhardt et al. (2018): Cause or consequence? Disentangling the
      relationship between psychosis and substance use.

PMID- 29638035
TI  - Post-thyroidectomy suture granuloma: A diagnosis on fine needle aspiration
      cytology.
AB  - Suture granulomas result from the use of nonabsorbable suture and is an
      infrequent complication following thyroidectomy. When they occur, suture
      granulomas may mimic both benign and malignant diagnoses, posing a potential
      diagnostic challenge. Ultrasound-guided fine needle aspiration cytology is an
      accurate diagnostic modality for the workup of nodules within the thyroidectomy
      bed. We herein present 2 cases of post-thyroidectomy suture granulomas,
      presenting as a painless, palpable mass in the surgical bed and occurring as a
      late complication of thyroidectomy that were diagnosed on fine needle aspiration
      cytology.

PMID- 29638036
TI  - Diagnosis of pseudo-gout (calcium pyrophosphate deposition disease) clinched on
      cytology.
AB  - Calcium pyrophosphate dihydrate (CPPD) deposition disease is a metabolic
      arthropathy which results from deposition of calcium pyrophosphate crystals in
      and around joints especially the hyaline cartilage and disc material. This
      metabolic disease in uncommon in the smaller joints and multiple diagnostic
      modalities along with biochemical investigations would be necessary for definite
      diagnosis. We highlight the case of a 48 year old male who presented with a
      painful mass at the base of left thumb and was clinic-radiologically suspected as
      malignancy. Cytological examination (fine needle aspiration cytology [FNAC])
      showed numerous extracellular rods shaped and rhomboid blunt-ended crystals along
      with foreign body type of giant cells. The main emphasis here is on the pivotal
      role played by FNAC in accurately diagnosing the disease where other modalities
      like radiology and histopathology failed to do so. The exact categorization of
      crystals is important from treatment point of view to avoid any major deformities
      in the joints/systemic manifestation.

PMID- 29638037
TI  - Robust Production of Ultrahigh Surface Area Carbon Sheets for Energy Storage.
AB  - Nanostructured carbon materials play essential roles in electrochemical energy
      storage devices. However, scalable production of high surface area carbon with a
      cost-effective process while controlling the morphology is challenging. Herein, a
      one-step procedure to produce carbon sheets with very high specific surface area
      up to 3411 m2 g-1 by direct pyrolysis of dipotassium ethylene diamine
      tetraacetate is reported. Unlike that of biomass-pyrolyzed carbons, the surface
      area of prepared carbon sheets is not sensitive to pyrolysis conditions (e.g.,
      heating temperature and time), which makes the production robust and scalable.
      Moreover, the pore structure is stable against posttreatments, including solvent
      washing, which are detrimental to that of graphene-based soft sheet assemblies.
      When used as supercapacitor electrodes, the ultrahigh surface area carbon sheets
      (HSACS) show a high specific capacitance of 268 F g-1 at 5 mV s-1 , and retain
      70% of the capacitance at 100 times higher scan rate in 6 m KOH aqueous
      electrolyte. Furthermore, the HSACS also exhibit a high specific capacitance of
      266 F g-1 within a 1.6 V symmetric supercapacitor potential window in 2 m Li2 SO4
      aqueous electrolyte. The symmetric supercapacitor delivers a maximum specific
      energy of 23.6 W h kg-1 and high power density of 6.4 kW kg-1 .

PMID- 29638038
TI  - Genetic characterization of a novel group of avastroviruses in geese.
AB  - As part of aetiological studies, we tested 28 samples collected from domestic
      geese showing enteritis and sporadic death. A novel group of avastroviruses was
      found in six samples. One isolate was completely sequenced, which comprised 7,148
      nucleotides. Pairwise comparisons and phylogenetic analysis demonstrated that the
      goose astrovirus is highly divergent from all previously described
      avastroviruses. Our data support the view that domestic geese can be infected by
      astroviruses with different genetic backgrounds, and have raised a concern about
      the role of domestic geese as reservoirs for diverse astroviruses.

PMID- 29638039
TI  - Engineering a pH-Sensitive Liposomal MRI Agent by Modification of a Bacterial
      Channel.
AB  - MscL is a bacterial mechanosensitive channel that serves as a cellular emergency
      release valve, protecting the cell from lysis upon a drop in external osmolarity.
      The channel has an extremely large pore (30 A) and can be purified and
      reconstituted into artificial membranes. Moreover, MscL is modified to open in
      response to alternative external stimuli including changes in pH. These
      properties suggest this channel's potential as a triggered "nanopore" for
      localized release of vesicular contents such as magnetic resonance imaging (MRI)
      contrast agents and drugs. Toward this end, several variants of pH-triggered MscL
      nanovalves are engineered. Stealth vesicles previously been shown to evade normal
      in vivo clearance and passively accumulate in inflamed and malignant tissues are
      reconstituted. These vesicles are loaded with 1,4,7,10-tetraazacyclododecane
      tetraacetic acid gadolinium complex (Gd-DOTA), an MRI contrast reagent, and the
      resulting nanodevices tested for their ability to release Gd-DOTA as evidenced by
      enhancement of the longitudinal relaxation rate (R1 ) of the bulk water proton
      spins. Nanovalves that are responsive to physiological pH changes are identified,
      but differ in sensitivity and efficacy, thus giving an array of nanovalves that
      could potentially be useful in different settings. These triggered nanodevices
      may be useful in delivering both diagnostic and therapeutic agents.

PMID- 29638040
TI  - An unusual case of anemia in a cardiac transplant recipient.
AB  - Anemia is a well-described comorbidity in patients with heart failure and has
      been associated with decreased survival rates after heart transplant. The causes
      of anemia are broad, and identification of the underlying etiology is critical
      for management. Herein, we report an unusual case of severe anemia complicating
      cardiac transplantation.

PMID- 29638041
TI  - L-rhamnose induces browning in 3T3-L1 white adipocytes and activates HIB1B brown
      adipocytes.
AB  - Induction of the brown adipocyte-like phenotype in white adipocytes (browning) is
      considered as a novel strategy to fight obesity due to the ability of brown
      adipocytes to increase energy expenditure. Here, we report that L-rhamnose
      induced browning by elevating expression levels of beige-specific marker genes,
      including Cd137, Cited1, Tbx1, Prdm16, Tmem26, and Ucp1, in 3T3-L1 adipocytes.
      Moreover, L-rhamnose markedly elevated expression levels of proteins involved in
      thermogenesis both in 3T3-L1 white and HIB1B brown adipocytes. L-rhamnose
      treatment in 3T3-L1 adipocytes also significantly elevated protein levels of p
      HSL, p-AMPK, ACOX, and CPT1 as well as reduced levels of ACC, FAS, C/EBPalpha,
      and PPARgamma, suggesting its possible role in enhancement of lipolysis and lipid
      catabolism as well as reduced adipogenesis and lipogenesis, respectively. The
      quick technique of efficient molecular docking provided insight into the strong
      binding of L-rhamnose to the fat-digesting glycine residue of beta3 -adrenergic
      receptor (AR), indicating strong involvement of L-rhamnose in fat metabolism.
      Further examination of the molecular mechanism of L-rhamnose revealed that it
      induced browning of 3T3-L1 adipocytes via coordination of multiple signaling
      pathways through beta3 -AR, SIRT1, PKA, and p-38. To the best of our knowledge,
      this is the first study to demonstrate that L-rhamnose plays multiple modulatory
      roles in the induction of white fat browning, activation of brown adipocytes, as
      well as promotion of lipid metabolism, thereby demonstrating its therapeutic
      potential for treatment of obesity. (c) 2018 IUBMB Life, 70(6):563-573, 2018.

PMID- 29638042
TI  - Microfluidic enrichment of plasma cells improves treatment of multiple myeloma.
AB  - Cytogenetic alterations form the basis for risk stratification for multiple
      myeloma (MM) and guide the selection of therapy; however, current pathology
      assays performed on bone marrow samples can produce false-negatives due to the
      unpredictable distribution and rarity of MM cells. Here, we report on a
      microfluidic device used to facilitate CD45 depletion to enhance the detection of
      cytogenetic alterations in plasma cells (PCs). Bone marrow samples from 48
      patients with MM were each divided into two aliquots. One aliquot was subjected
      to classic flow cytometry and fluorescent in situ hybridization (FISH). The other
      first went through CD45+ cell depletion, further enriched by microfluidic size
      selection. The enriched samples were then analyzed using flow cytometry and FISH
      and compared to those analyzed using the classic method only. Unlike the
      traditional method, the microfluidic device removed the CD45+ leukocytes and
      specifically selected PCs from the remaining white blood cells. Therefore, the
      microfluidic method (MF-CD45-TACs) significantly increased the percentage of
      CD38+ /CD138+ cells to 37.7 +/- 20.4% (P < 0.001) from 10.3 +/- 8.5% in bone
      marrow. After the MF-CD45-TAC enrichment, the detection rate of IgH
      rearrangement, del(13q14), del(17p), and 1q21 gains, rose to 56.3% (P < 0.001),
      37.5% (P < 0.001), 22.9% (P < 0.001), and 41.7% (P = 0.001), respectively; all
      rates of detection were significantly increased compared to the classically
      analyzed samples. In this clinical trial, this microfluidic-assisted assay
      provided a precise detection of cytogenetic alterations in PCs and improved
      clinical outcomes.

PMID- 29638043
TI  - Assessing the usefulness of B-mode and colour Doppler sonography, and
      measurements of circulating progesterone concentrations for determining ovarian
      responses in superovulated ewes.
AB  - The main goal of this study was to assess the usefulness of two imaging
      modalities, namely the B-mode and colour Doppler sonography, and serum
      progesterone (P4 ) concentrations for determining the ovarian response in
      superovulated ewes. Twenty-four sexually mature Santa Ines ewes underwent the
      superovulatory treatment consisting of eight injections of porcine FSH (total
      dose of 200 or 133 or 100 mg; n = 8 ewes/total dose) given at 12-hr intervals and
      initiated 48 hr before CIDR(r) (Pfizer Inc., Auckland, New Zealand) removal. Six
      days after natural mating, the ovaries of all donor ewes were visualized and
      examined with transrectal ultrasonography and then with videolaparoscopy to
      identify and enumerate corpora lutea (CL) and luteinized unovulated follicles
      (LUFs). Jugular blood samples were collected just prior to ovarian examinations.
      The total number of CL (r = .78 and 0.83, p < .0001) and LUFs (r = .74 and 0.90,
      p < .0001) enumerated using the B-mode and colour Doppler ultrasonographic
      technique, respectively, were correlated with that ascertained by
      videolaparoscopy. Circulating concentrations of P4 were related directly to the
      number of healthy CL (r = .73, p = .0002) and inversely to the number of
      prematurely regressing CL (r = -.46, p = .03), but the accuracy of predicting the
      number of short-lived CL with serum P4 concentrations was very poor. The present
      results indicate that ultrasonographic imaging and serum P4 measurements on the
      day of embryo recovery are useful indicators of total/normal CL numbers and both
      ultrasonographic techniques can be used to quantify LUFs in superovulated ewes.

PMID- 29638044
TI  - Undiagnosed HIV infections among gay and bisexual men increasingly contribute to
      new infections in Australia.
AB  - INTRODUCTION: We determined the contribution of undiagnosed HIV to new infections
      among gay and bisexual men (GBM) over a 12-year period in Australia where there
      has been increasing focus on improving testing and HIV treatment coverage.
      METHODS: We generated annual estimates for each step of the HIV cascade and the
      number of new HIV infections for GBM in Australia over 2004 to 2015 using
      relevant national data. Using Bayesian melding we then fitted a quantitative
      model to the cascade and incidence estimates to infer relative transmission
      coefficients associated with being undiagnosed, diagnosed and not on ART, on ART
      with unsuppressed virus, or on ART with suppressed virus. RESULTS: Between 2004
      and 2015, we estimated the percentage of GBM with HIV in Australia who were
      unaware of their status to have decreased from 14.5% to 7.5%. During the same
      period, there was a substantial increase in the number and proportion of GBM
      living with HIV on treatment and with suppressed virus, with the number of
      virally suppressed GBM increasing from around 3900 (30.2% of all GBM living with
      HIV) in 2004 to around 14,000 (73.7% of all GBM living with HIV) in 2015. Despite
      the increase in viral suppression, the annual number of new infections rose from
      around 660 to around 760 over this period. Our results have a wide range due to
      the uncertainty in the cascade estimates and transmission coefficients.
      Nevertheless, undiagnosed GBM increasingly appear to contribute to new
      infections. The proportion of new infections attributable to undiagnosed GBM
      almost doubled from 33% in 2004 to 59% in 2015. Only a small proportion (<7%)
      originated from GBM with suppressed virus. DISCUSSION: Our study suggests that an
      increase in HIV treatment coverage in Australia has reduced the overall risk of
      HIV transmission from people living with HIV. However, the proportion of
      infections and the rate of transmission from undiagnosed GBM has increased
      substantially. These findings highlight the importance of HIV testing and
      intensified prevention for Australian GBM at high risk of HIV.

PMID- 29638046
TI  - Bacteriological findings in the canine uterus during Caesarean section performed
      due to dystocia and their correlation to puppy mortality at the time of
      parturition.
AB  - Canine intrauterine bacteriological flora during dystocia is unknown. Thus,
      frequency (bacterial growth (not) detected), quality (species and number of
      different bacterial isolates) and quantity (colony-forming units) of intrauterine
      bacteria in relation to in utero foetal death in 50 bitches undergoing emergency
      Caesarean section were investigated. Bacterial growth was quantified from single
      colonies, (+) (0.5), to strong growth, +++ (3) and was observed in 34 bitches
      (68%), with Staph. epidermidis (n = 12), Staph. intermedius-group (n = 7), beta
      haemolytic streptococci (n = 6), Staph. aureus, alpha- and gamma-haemolytic
      streptococci (n = 4 each) being most common and one to four bacteria per sample.
      Regarding the quantity, most often (n = 46) low growth was identified. In bitches
      with living pups only (group I), mean number of isolates was 0.78 +/- 0.83
      compared to 1.60 +/- 1.10 (living + stillborn pups, group II) and 1.0 +/- 1.15
      (stillborn pups only, group III) and mean bacterial growth in groups I/II/III was
      + (1.0, quantity), + (1.4) and ++ (1.6). Taking just positive samples into
      consideration, mean number of bacterial isolates was significantly higher in
      group II compared to I (p = .0088). We concluded that the canine uterus cannot be
      considered free of bacteria during dystocia. Mean numbers of different bacterial
      isolates and quantity of bacterial growth are higher in bitches with in utero
      foetal death.

PMID- 29638045
TI  - ACE inhibition in goats under fixed-time artificial insemination protocol
      increases the pregnancy rate and twin births.
AB  - To assess the effect of the angiotensin-converting enzyme (ACE) inhibition on the
      efficiency of the fixed-time artificial insemination (TAI), 69 goats were divided
      randomly into two groups: enalapril (n = 35) and control (n = 34). In the
      experiment, all animals underwent the protocol of fixed-time artificial
      insemination for 12 days. Enalapril group received enalapril maleate dissolved in
      saline (Enalapril, Lab Teuto Ltda) subcutaneously at the following doses: 0.2
      mg/kg/day in D0-D2; 0.3 mg/kg/day in D3-D6 and 0.4 mg/kg/day in D7-D11. The
      control group received the corresponding volume of 0.9% saline solution. We
      performed a single insemination 36 hr after sponge removal using frozen semen
      from two adult male goats with recognized fertility. The ultrasound pregnancy
      diagnosis was 30 days after the artificial insemination (AI). There was
      significant increase in pregnancy rates and twinning as well as a decrease in
      foetal loss in animals receiving enalapril (p < .01). The use of ACE inhibitors
      during the TAI protocol was shown to be a promising alternative to increase the
      efficiency of such reproductive biotechnology.

PMID- 29638047
TI  - In vivo study of self-assembled alkylsilane coated degradable magnesium devices.
AB  - Magnesium (Mg) and its alloys are candidate materials for resorbable implantable
      devices, such as orthopedic devices or cardiovascular stents. Mg has a number
      advantages, including mechanical properties, light weight, its osteogenic effects
      and the fact that its degradation products are nontoxic and naturally present in
      the body. However, production of H2 gas during the corrosion reaction can cause
      formation of gas pockets at the implantation site, posing a barrier to clinical
      applications of Mg. It is therefore desirable to develop methods to control
      corrosion rate and gas pocket formation around the implants. Here we evaluate the
      potential of self-assembled multilayer alkylsilane (AS) coatings to control Mg
      device corrosion and formation of gas pockets in vivo and to assess effects of
      the AS coatings on the surrounding tissues in a subcutaneous mouse model over a 6
      weeks' period. The coating significantly slowed down corrosion and gas pocket
      formation as evidenced by smaller gas pockets around the AS coated implants
      (ANOVA; p = 0.013) and decrease in the weight loss values (t test; p = 0.07).
      Importantly, the microCT and profilometry analyses demonstrated that the coating
      inhibited the pitting corrosion. Specifically, the roughness of the coated
      samples was ~30% lower than uncoated specimen (p = 0.02). Histological assessment
      of the tissues under the implant revealed no inflammation or foreign body
      reaction. Overall, our results demonstrate the feasibility of use of the seld
      assembled AS coatings for reduction of gas pocket formation around the resorbable
      Mg devices. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl
      Biomater, 2018.

PMID- 29638048
TI  - Tissue reaction after subcutaneous implants of a new material composed of
      ethylene-vinyl acetate and starch for future use as a biomaterial.
AB  - This study aimed to evaluate the tissue reaction of ethylene-vinyl acetate (EVA)
      in 4 different compositions and processing: EVA foamed at high pressure with
      ultrasound (EVACU); EVA with 15% starch foamed at high pressure with ultrasound
      (EVAMCU); EVA with 15% starch foamed at high pressure without ultrasound and EVA
      foamed at high pressure without ultrasound as future use as a porous scaffold.
      Scanning electron microscopy images showed the influence of starch, reducing the
      diameter of pores. The number of open pores was also reduced with the addition of
      starch. The ultrasound applied during the manufacturing of composites does not
      affect these characteristics. Eighteen rats were used to test the tissue reaction
      of materials and PTFE (polytetrafluoroethylene), proven biocompatible material.
      After 7, 15, and 60 days of surgery, the materials were removed and processed for
      microscopic evaluation and counting of the inflammatory infiltrate. The data
      shows inflammatory reaction similar to PTFE. However, in the quantitative
      analysis at 60 days, the EVACU and EVAMCU showed less quantity of mononuclear
      cells (p < 0.05). Thus, the results suggest that the use of ultrasound in the
      production method (EVA) seems to have improved cell behavior regarding the
      reduction of infiltration over the period, with tissue response equivalent to the
      PTFE. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater,
      2018.

PMID- 29638049
TI  - Visual Evoked Potentials and Glaucoma.
AB  - Visual evoked potentials (VEP) can be used to assess the function of the visual
      system objectively. Research on VEP testing as a method of glaucoma evaluation
      has been performed for many years. Pattern VEP has shown good specificity and
      sensitivity in the detection of glaucoma in some studies, but other studies have
      not shown similar efficacy. Multifocal VEP can produce a topographical measure of
      glaucomatous damage and has been shown to be able to detect a similar number of
      defects in patients with glaucoma or ocular hypertension as compared with the
      visual field test. Despite promising data on these VEP test modalities in the
      assessment of glaucoma, multiple aspects of test administration make their
      routine use impractical in a clinical setting. New VEP testing modalities, such
      as short-duration transient VEP and isolated-check VEP, allow the test to be
      performed more quickly and easily. Further research on these more recent
      technologies may allow us to use VEP effectively in the diagnosis and management
      of glaucoma.

PMID- 29638050
TI  - EVOLVING SCENARIO OF PHARMACEUTICAL CARE IN PAKISTAN AND OTHER COUNTRIES: HEALTH
      IMPACT ASSESSMENT IN PUBLIC HEALTH PRACTICE.
AB  - Worldwide, pharmaceutical care has been recognized as the primary mission of
      pharmacy. According to the philosophy of pharmaceutical care, pharmacist is not
      only responsible to dispense the medicines but also responsible to improve the
      patient's quality of life. Pharmaceutical care practice is required to be
      introduced in the developing countries to decrease drug related mortality and
      morbidity. This paper aimed to highlight the quality of pharmaceutical care
      practice in the developing countries, predominantly in Pakistan. The paper
      highlights the health status and current scenario and barriers to pharmaceutical
      care practice in Pakistan. Pharmacists in Pakistan are not much involved in the
      provision of pharmaceutical care services due to a number of barriers that
      include insufficient number of pharmacists, lack of proper time, inadequate
      skills and training, lack of fmancial support and limited recognition of
      pharmacists in the public. A majority of community pharmacies are running without
      a pharmacist under the supervision of unprofessional personnel.

PMID- 29638051
TI  - QUANTIFICATION AND PHARMACOKINETICS OF 1 -METHYLPYRIDINIUM AND 1,4
      DIMETHYLPYRIDINIUM IN RATS BY LIQUID CHROMATOGRAPHY TANDEM MASS SPECTROMETRY.
      TISSUE DISTRIBUTION OF 1,4-DIMETHYLPYRIDINIUM IN RATS.
AB  - A sensitive and specific liquid chromatography tandem mass spectrometry method
      for quantification of 1-methylpyridinium (1-MP) and 1,4-dimethylpyridinium (1,4
      DMP) in rat plasma and tissues homogenates was developed. Chromatographic
      separation was performed on an Aquasil C18 analytical column with an isocratic
      elution of acetonitrile and water, both with an addition of formic acid (0.1%,
      v/v). Detection was achieved by triple quadrupole mass spectrometer TSQ Quantum
      Ultra equipped with a heated electrospray ionization source (HESI). The limit of
      quantification for both compounds was 0.05 pg/mL in plasma and 0.25 MUg/g in
      studied tissues. The method was applied to pharmacokinetics and bioavailability
      of both 1-MP and 1,4-DMP with tissue distribution of 1,4-DMP in rats.
      Pharmacokinetic studies of 1-MP and 1,4-DMP were carried out following their
      intravenous or intragastric administration to male Wistar rats at the dose of 100
      mg/kg. The terminal half-lives of I-MP and 1,4-DMP after their intravenous
      administration were 55.3 and 70.8 min, respectively. The absolute bioavailability
      was 51 and 31% for t-MP and 1,4-DMP, respectively.

PMID- 29638052
TI  - DETERMINATION OF TENOXICAM IN THE PLASMA BY REVERSE PHASE HPLC METHOD USING
      SINGLE STEP EXTRACTION TECHNIQUE: A RELIABLE AND COST EFFECTIVE APPROACH.
AB  - A simple and cost effective RPLC-UV bio-analytical method was developed and used
      for tenoxicam quantification on ODS Hypersil C-18 column using classical liquid
      liquid extraction technique for sample preparation. Acetonitrile was used as
      precipitating agent for plasma proteins and supernatant was taken for injection
      without any further modification. The bio-analytical method depends upon
      isocratic elution using binary mixture of aqueous 0.1 M potassium dihydrogen
      phosphate and acetonitrile in 6 : 4 ratio. The pH of mobile phase was adjusted to
      2.8 which favor tenoxicam to remain undissociated throughout the analysis. The
      optimized flow rate of 1.0 mL/min provided proper separation of peaks and column
      clean up within 5 min. The UV detection was achieved at 381 nm and 4.29 min.
      Reproducible calibration curve gave 0.325 MUg/mL LOQ, linear dynamic range from
      0.325 to 20 MUg/mL and recovery from plasma was 98.5% with %CV 0.2314 achieved.
      After validation, the method was applied in pharmacokinetic study in healthy
      human volunteers (n = 8). The pharmacokinetic parameters were evaluated using
      kinetica version 4.1.1. The values of C. and area under curve for current study
      were 1.776 +/- 0.003 pg/mL and 179.97 +/- 0.0681 (mean +/- SEM) pg x h/mL. The
      values of t, and volume of distribution for tenoxicam in current study were
      74.103 0.167 h (mean +/- SEM) and 11.962 +/- 0.0677 L/kg (mean +/- SEM),
      respectively. This method was simple, sensitive and successfully applied in
      pharmacokinetic studies. It can be extended to bioequivalence studies and
      evaluation of tenoxicam in different clinical situations.

PMID- 29638053
TI  - THE EFFECT OF METHANOL USED AS VEHICULUM ON SERUM PHENACETIN CONCENTRATION IN THE
      RAT.
AB  - The xenobiotic absorption process is dependent on many factors, related both to
      the substance and form of its administration. During administration of small
      amounts of drugs, the effect of vehiculum on drug fate in the body becomes also
      evident. The intensity of absorption depends on numerous factors not necessarily
      related to the substance and its formulation, and also on biotransformation and
      active transport processes. Additional problem is the fact that many medicines
      are lipophilic compounds and insoluble in the water (e.g. phenacetin). Methanol
      and its aqueous solutions facilitate administration to the experimental animals,
      in the dissolved form of a number of medicines practically insoluble in water.
      Taking into consideration that methanol is particularly for rats, of low
      toxicity, it is quite frequently applied as vehiculum. The aim of this study was
      to investigate the potential interactions that may occur during the use of
      methanol as vehiculum and compare changes when were used solution 1% of
      carboxymethylcellulose. The study was performed on male Wistar rats. The tests
      were performed using phenacetin, which is recognized as biomarker of CYP 2E 1
      isoform activity. Phenacetin was given per os in a single dose of 100 mg/kg b. w.
      Various procedures of phenacetin administration were tested, including
      solubilization in methanol or suspension in 1% water solution of
      carboxymethylcellulose. The results of this study show that methanol influences
      the phenacetin bioavailability and kinetics. Comparing the administration of this
      drug in methanol solutions against 1% of carboxymethylcellulose, it is in the
      case of phenacetin triple increase in AUC0-4 h. The presence of methanol affects
      the shape of kinetic curves of phenacetin causing higher their course until 4
      hours after administration.

PMID- 29638054
TI  - CYTOTOXIC AND GENOTOXIC STUDIES OF QUERCETIN, QUERCETIN SODIUM SALT AND QUERCETIN
      COMPLEXES WITH NICKEL (II) AND ZINC (II).
AB  - The aim of this study was to compare the cyto- and genotoxic effects of
      quercetin, quercetin sodium salt as well as its complexes with nickel (II) and
      zinc (II) with the use of Escheiichia coli K-12 recA::gfp microbial biosensor
      strain containing transcriptional fusion between DNA-damage genotoxin-inducible
      recA promoter involved in the SOS regulon response and fast folding GFP (green
      fluorescent protein) variant reporter gene - gfpnmt2. Obtained results indicate
      that recA::gfpmut2 genetic system was a sensitive biosensor to the most of tested
      chemicals. The complex of quercetin with sodium, nickel and zinc increased (and
      in some cases modulated) the reactivity of ircA promoter in relation to control
      sample. The results indicated that E. coli K-12 iecA::gfp mut2 strain could be
      potentially useful for monitoring of cytotoxic and genotoxic effect of some
      biological natural compounds, potentially used in anticancer chemoprevention and
      therapy.

PMID- 29638055
TI  - DESIGN, SYNTHESIS AND ANTICANCER ACTIVITY OF SOME NOVEL 1,2,4-TRIAZOLES CARRYING
      BIOLOGICALLY ACTIVE SULFONAMIDE MOIETIES.
AB  - Thirteen novel 1, 2, 4-triazoles incorporating a biologically active sulfonamide
      moieties 1-13 were designed and synthesized. The structures of the prepared
      compounds were elucidated on the basis of elemental analyses, IR, 'H-NMR, "C-NMR
      and mass spectral data. All the newly synthesized compounds were evaluated for
      their in vino anticancer activity against various cancer cell lines. The
      corresponding triazole carrying a biologically active free sulfonamide with
      unsubstituted phenyl ring 1 and triazole bearing sulfonamide with
      dimethylpyrimidine 11 were the most potent in this study which showed higher
      activity than the reference drug 2',7'-dichlorofluorescein (DCF). Cytotoxic
      screening of the tested compounds could offer an encouraging framework in the
      field that may lead to the discovery of potent anticancer activity.

PMID- 29638056
TI  - SYNTHESIS AND ANTIMICROBIAL ACTIVITY OF 5-SUBSTITUED 4-THIAZOLIDINONES WITH
      SULFANILAMIDE PHARMACOPHORE.
AB  - After incorporation pharmacophores of allylamine and sulfanilamide into 4
      thiazolidinone's ring - no antimicrobial activity was determined. This outcome
      stimulated synthesis of new group - 5-substituted 4-thiazolidinones. In the
      literature it is noted that the fragment of aldehyde in 5 position of 4
      thiazolidinone's ring should give or increase biological activity. So, it was
      decided to incorporate fragment of aldehyde into 4-thiazolidinone's ring together
      with sulfanilamide pharmacophore, investigate antimicrobial activity and compare
      it with initial compounds - sulfanilamides. It was established that new compounds
      suppressed growth of S. arteus, E. coli, B. subtilis, P. mirabilis, C. albicans.
      Sulfanilamide, sulfapyridine and/or 2-chlorobenzaldehyde were incorporated into
      the structure of the most active compounds. It was concluded that synthesis of 4
      thiazolidinones substituted by aldehyde in 5 position and sulfanilamide in 2
      position are not potential antimicrobial agents.

PMID- 29638057
TI  - SYNTHESIS, BIOLOGICAL EVALUATION AND MOLECULAR DOCKING STUDIES OF AROMATIC
      SULFONAMIDE DERIVATIVES AS ANTI-INFLAMMATORY AND ANALGESIC AGENTS.
AB  - In this study, [4-(N-substituted sulfamoyl)phenyl]carbonohydrazonoy dicyanides 3a
      c were synthesized and condensed with various hydrazine hydrate derivatives to
      produce the corresponding 3,5-diaminopyrazole derivatives 4-9, respectively.
      Furthermore, condensation of 3b with ax-naphthol, urea and thiourea yielded the
      pyrimidine derivatives 10 and 11a,b, respectively. Also, condensation of 3b with
      hydroxylamine hydrochloride produced the isoxazole derivative 12. Treatment of 3b
      with different secondary amines afforded the piperidine and piperazine
      derivatives 13a-c, respectively, while its condensation with diamines yielded the
      corresponding diazepine, benzodiazepine and benzooxazepine derivatives 14-16.
      Reaction of 3b with malononitrile or diazonium salt 2b with MND followed by
      treatment with malononitrile afforded the pyrido-pyridazine derivative 18. Anti
      inflammatory and analgesic evaluation of some of the synthesized compounds as
      representative examples exhibited equipotent activity to that of the reference
      drug celecoxib. The ulcerogenic potential of the tested derivatives showed a
      complete safety profile on G.I.T. system. Molecular docking studies showed that
      the tested compounds induced good fitting and forming different hydrogen bonds
      with the amino acid residues at the active sites of COX-2 enzyme.

PMID- 29638058
TI  - SYNTHETIC DERIVATIVES OF ISOQUINOLINE, DICARBOXYLIC ACID IMIDES AND THIOIMIDES AS
      BIOACTIVE COMPOUNDS.
AB  - This study is a continuation of a research program aimed at identifying potent
      drugs against bacterial infections, in which a series of organic compounds:
      dicarboxylic acid imides and thioimides, isoquinoline derivatives and open chain
      compounds, were examined for antimicrobial properties against Staphylococcus
      auneus and Escheiichia coli. In effect of this investigation, the most active
      compounds (35-40, 47) were selected for in vitiv tests against fourteen
      clinically important pathogenic isolates, the methicillin resistant
      Staphylococcus aueus (MRSA) and several reference Gram-negative bacteria: Prteus
      vulgaris, Pseudomonas aeruginosa, Klebsiella pneumonia, Stenonophoinonas
      inaltophilia, and Acinetobacter baumannii. The obtained data revealed that seven
      compounds (three dithioimides, 35, 39, 47, and four thioimides, 36-38, 40)
      exhibit effective antibacterial activity against the tested Staphylococcus auirus
      MSSA and MRSA strains. Among them, dicarboxylic acid thioimides 37 and 38 were
      proven to be the most active.

PMID- 29638059
TI  - IN SILICO ADME STUDIES OF POLYAMINE CONJUGATES AS POTENTIAL ANTICANCER DRUGS.
AB  - The ADME properties and drug-likeness of several polyamine derivatives containing
      dimeric phthalimide, quinoline, cinnoline and chromone moieties with three
      different polyamines: 1,4-bis(3-aninopropyl)piperazine, 4,9-dioxa-1,12
      dodecanediamine and 3,3-diamino-N-methyldipropylamine as linkers were presented.
      These compounds are structurally related to DNA bisintercalators, a group of
      agents with anti-cancer activity. Their biological properties were previously
      assessed in vitio in a highly aggressive melanoma cell line A375. Current studies
      evaluate their potential to be qualified as drugs by performing in silico ADME
      screening. The research is carried out using Discovery Studio 3.0 ADMET protocol
      obtained from Accelrys and might be useful for further developing and
      optimization of potential anticancer drugs.

PMID- 29638060
TI  - SYNTHESIS AND IMMUNOREGULATORY PROPERTIES OF SELECTED 5-AMINO-3-METHYL-4
      ISOXAZOLECARBOXYLIC ACID BENZYLAMIDES.
AB  - The aim of the study was to characterize a series of isoxazole derivatives in
      several immunological tests in vitro and in vivo, in mouse and human models. The
      human model included measurement of: viability of peripheral blood mononuclear
      cells (PBMC), phytohemagglutinin A (PHA)-induced proliferation of PBMC,
      production of tumor necrosis factor a (TNF a) in whole blood cultures stimulated
      with lipopolysaccharide (LPS) and growth of SW-948 and L1210 tumor cell lines.
      Experiments in mice encompassed the following tests: secondary, humoral immune
      response splenocytes to sheep erythrocytes (SRBC) in vitiv, delayed type
      hypersensitivity (DTH) to ovalbumin (OVA) and carrageenan-induced foot edema. All
      compounds were non-toxic against PMBC and displayed differential, dose-dependent
      suppressive properties in the model of PHA- induced PMBC proliferation. They also
      exhibited differential, mostly inhibitory effects on TNF a production. The
      inhibitory actions on growth of tumor cell lines were moderate. M05 (5-amino-3
      methyl-N-(4-methyl-benzyl)-4-isoxazolecarboxamide) was most suppressive in the
      proliferation and TNF a production tests, it was, therefore, selected for in
      vitro and in vivo studies in the mouse models. The compound inhibited the humoral
      immune response in vitro, stimulated the inductive phase of DTH in vivo, although
      it inhibited the eliciting phase of that response. The compound also inhibited
      the carrageenan skin reaction. M05 combines strong anti-proliferative and anti
      inflammatory activities, it is therefore attractive for further studies in more
      advanced animal models as a potential therapeutic.

PMID- 29638062
TI  - ANTIOXIDANT, ANTIBACTERIAL AND GUT MODULATING ACTIVITIES OF KALANCHOE LACINIATA.
AB  - Kalanchoe laciniata (L.) DC. (Crassulaceae) is a widely distributed plant in
      Africa and Asia. Traditionally, various communities use this plant for the
      treatment of a variety of ailments such as gut prob- lems, allergic conditions
      and wounds. The current study was designed to explore the antibacterial,
      antioxidant and gut modulating activities of K. laciniata in order to provide
      scientific rationale for its traditional uses. Phytochemical compounds were
      assessed through screening 70% crude methanolic extract of K. laciniata. Its gut
      modulatory activity was evaluated by in vitro tissue experiments on rabbit
      jejunum which yielded maximal spasmogenic response of 28.4 +/- 4.6% (n = 4) at 3
      mg/mL, while spasmolytic response was recorded with EC50 value of 3.2 mg/mL (2.8
      3.5, 95% CI, n = 5). In antibacterial assays crude extract was found effective
      against Stapllococcus aurus and Bacillus subtilis, with MIC value of 5 and 2.5
      mg/mL, respectively. The testing of the methanolic crude extract for antioxidants
      resulted in total phenolic contents of 27.8 +/- 1.8 mg GAE/g DW and 22.7 +/- 2.1
      mg AAE/g DW total antioxidant activity. It also scavenged 17.3 +/- 3.0% of DPPH
      free radical when compared with quercitin.

PMID- 29638061
TI  - ASSESSMENT OF SOME BIOLOGICAL ACTIVITIES OF ALYSSUM L. KNOWN AS MADWORT.
AB  - In this research the phenolic composition, and antioxidant, antibacterial and
      cytotoxic activities of the methanolic extracts obtained from three Alyssum L.
      taxa (A.foliosum var. megalocaipum, A. simplex and A. stHgosum subsp. stfigosum)
      were investigated for the first time. The antioxidant activity of the extracts
      was evaluated by DPPH, metal chelating, phosphomolybdenum, P-carotene/linoleic
      acid and ferric reducing power assays. In addition, total phenolic and flavonoid
      contents in the extracts were determined. The brine shrimp lethality test was
      used to screen for possible cytotoxic activity of the extracts. Also, the
      extracts were evaluat- ed for cytotoxicity against three human cancer cell lines:
      MCF-7, H1299 and HeLa. HPLC analysis showed that cinnamic acid, chlorogenic acid
      and rutin were the major phenolics in extracts tested. Among the three Alyssum
      extracts evaluated, the highest biological activities were obtained from A.
      simplex compared to other two Alyssum L. taxa. Based upon its name, future
      studies will be targeted at investigating which components can be caused
      neurorehabilitation in Alyssum.

PMID- 29638063
TI  - EFFECT OF JASMONIC ACID ON TOTAL PHENOLIC CONTENT AND ANTIOXIDANT ACTIVITY OF
      EXTRACT FROM THE GREEN AND PURPLE LANDRACES OF SWEET BASIL.
AB  - Basil (Ocimum basilicun L.) belongs to the family Lamiaceae and is an important
      aromatic and medicinal plant, which it widely cultivated in many countries. This
      plant is a good source of phenolic com- pounds and natural antioxidants. The main
      aim of present study was to determine effect of jasmonic acid on total phenolic
      content and antioxidant activity of ethanolic extract from the aerial parts of
      the purple and green landraces of basil. The pot experiment was conducted in an
      experimental field with cold and semiarid climate in southwestern Iran.
      Treatments comprised control (water), ethanol as solvent, 200 and 400 pLjasmonic
      acid. The total phenolic content of the extract by Folin-Ciocalteu method and the
      antioxidant activity using DPPH assay were determined. Results indicated that the
      different levels of jasmonic acid had significant effects on total phenolics
      content and antioxidant activity of the extracts. Foliar-applied jasmonic acid in
      particular 400 MUL increased total phenolic content in the plants as compared to
      untreated plants. In conclusion, it is suggested that jasmonic acid as an abiotic
      elicitor could be a promising material used to increase biological activity and
      pro-health functional value of basil plants.

PMID- 29638064
TI  - ANTI-OXIDATIVE, (alpha-GLUCOSIDASE AND alpha-AMYLASE INHIBITORY ACTIVITY OF VITEX
      DONIANA: POSSIBLE EXPLOITATION IN THE MANAGEMENT OF TYPE 2 DIABETES.
AB  - Vitex doniana is an important African medicinal plant traditionally used for the
      treatment of many diseases including type 2 diabetes (T2D). In this study, ethyl
      acetate, ethanol and aqueous extracts of the stem bark, root and leaf of V.
      doniana were analyzed for in vitro anti-oxidative activity and the results
      indicated that the ethanolic extract of the leaves had the best anti-oxidative
      activity. Subsequently, the ethanolic extract of the leaves was partitioned
      between hexane, dichloromethane, ethyl acetate and water. The aqueous fraction
      had a significantly ( p < 0.05) higher phenolics content and also showed the best
      anti-oxidative activity within the fractions. Furthermore, the aqueous fraction
      demonstrated significantly (p < 0.05) more potent inhibitory activities against
      alpha-glucosidase and alpha-amylase than other fractions. Steady state kinetics
      analysis revealed that the aqueous fraction inhibited both (alpha-glucosidase and
      (alpha-amylase activities in a non-competitive manner with inhibition binding
      constant (Ki) values of 5.93 and 167.44 MUg/mL, respectively. Analysis of the
      aqueous fraction by GC-MS showed the presence of resorcinol, 4-hydroxybenzoic
      acid, 3,4,5-trimethoxyphenol and 2,4'-dihydroxychalcone identified by their mass
      fragmentation patterns and comparison to standard spectra. The results obtained
      in this study showed that V doniana leaves have a good in vitro anti-T2D
      potential possibly elicited through phenolics.

PMID- 29638066
TI  - A STUDY OF COMPRESSION PROCESS AND PROPERTIES OF TABLETS WITH MICROCRYSTALLINE
      CELLULOSE AND COLLOIDAL SILICON DIOXIDE.
AB  - This paper compares the compressibility and properties of tablets from Prosolv
      SMCC 90 and a mixture of Avicel PH-102 and colloidal silicon dioxide with a
      different specific surface. The effect of an addition of the lubricant magnesium
      stearate on these parameters under varying conditions of mixing and the
      homogeneity of the lubricant in the mixtures are also examined. Compressibility
      is evaluated by means of the energy balance of the compression process; the
      examined properties of tablets are tensile strength and disintegration time. The
      total energy of compression was increased with compression force, the highest
      being in Prosolv SMCC 90. Its values did not differ for differing conditions of
      mixing with the lubricant. Plasticity was slightly decreased with compression
      force and in the mixture with magnesium stearate it was not influenced by the
      conditions of mixing. Tablets made from Prosolv SMCC 90 and Avicel PH-102 were
      stronger than those from the mixtures from Avicel PH-102 and both types of
      Aerosil. The addition of magnesium stearate markedly decreased the strength of
      tablets from Avicel PH-102. An increase in the period and frequency of mixing
      with the lubricant resulted in a further decrease in strength. Disintegration
      time was longer in tablets from Avicel PH-102 and Prosolv SMCC 90, and it was
      further prolonged by an addition of magnesium stearate.

PMID- 29638065
TI  - SECONDARY METABOLITES ISOLATED FROM TWO MEDICINAL PLANT SPECIES, BRIDELIA
      MICRANTHA AND SIDEROXYLON INERME AND THEIR ANTIOXIDANT ACTIVITIES.
AB  - The indigenous medicinal plant species, Bfidelia micrantha and Sideyoxylon ineime
      (both known as 'uMhlalamagwababa' in isiZulu), are used interchangeably by
      traditional healers in KwaZulu-Natal, South Africa, to treat a variety of
      ailments due to morphological similarities. In this study, a phytochemical
      investigation was done on B. inicrantha and S. inenne to determine if they have a
      chemotaxonomic link. Three penta- cyclic triterpenes, one carotenoid and one
      megastigmane were isolated from S. inerme. Two flavonoids and two triterpenes
      were isolated from B. micrantha. These compounds were not previously isolated
      from these plant species. The antioxidant capacity of the isolated flavonoids was
      comparable to that of the known antioxidant - ascorbic acid. Profiling of the
      fruit extracts from both plant species by gas chromatography-mass spectrometry
      showed different classes of compounds in the extracts. This study corroborates
      the use of S. inerme and B. mici-ntha by traditional healers but does not support
      their use interchangeably.

PMID- 29638067
TI  - RELATIVE BIOAVAILABILITY OF RISEDRONATE SODIUM ADMINISTERED IN SUPERABSORBENT
      COPOLYMER PARTICLES VERSUS ORAL SOLUTION TO NORMAL HEALTHY RABBITS.
AB  - In this study, sustained release superabsorbent copolymer particles have been
      prepared and analyzed to increase bioavailability of orally administered
      risedronate sodium. Formulations were prepared by free radical polymerization of
      combination of 2-hydroxyethyl methacrylate (HEMA), itaconic acid (IA), polyvinyl
      pyrrolidone (PVP) / chitosan (CTS) by using ethylene glycol dimethacrylate
      (EGDMA) as crosslinker, potassium persulfate as initiator, and N,N,N,N
      tetramethylethylene diamine as activator. Formulations were successfully loaded
      with risedronate sodium. Formulations as gel particles encapsulated in hard
      gelatin were analyzed to estimate drug content. The maximum plasma drug
      concentration (C.) and its corresponding time (Tmax.), area under the curve and
      relative bioavailability (with reference to oral solution of drug administered)
      were calculated. It was found a marked increase in Tmax. with lower Cmax. that
      confirmed the multiparticulte system to deliver drug at controlled rate. The
      results of relative bioavailability after oral administration of these
      formulations indicated a remarkable increase in the bioavailability.

PMID- 29638068
TI  - FORMULATION AND EVALUATION OF MICROSPHERES CONTAINING LOSARTAN POTASSIUM BY SPRAY
      DRYING TECHNIQUE.
AB  - Despite numerous applications of microspheres, few works devoted to the
      preparation of microspheres containing cardiac medications have been published.
      This study presents the potential of receiving microspheres containing losartan
      potassium, based on a matrix containing Eudragit L30D55. The study focuses on the
      possibilities of controlled release of losartan potassium from microspheres in
      order to reduce the dosage frequency, and also provides information on the effect
      of the addition of excipients to the quality of the microspheres. Microspheres
      are monolithic, porous or smooth microparticles ranging from 1 to 500 microns in
      size. For the preparation of microspheres containing losartan potassium, the
      spray-drying method was used. The performed study confirmed that the spray-drying
      technology used to obtain microspheres meets the criteria of size and morphology
      of the microparticles. The assessment of the kinetics of losartan potassium
      release from the examined microspheres demonstrated that the release profile
      followed the first- and/or zero-order kinetics. The use of spray-drying
      techniques as well as Eudragit L30D55 polymer matrix to obtain the microspheres
      containing losartan potassium makes it possible to obtain a product with the
      required particle morphology and particle size ensuring the release of the active
      substance up to 12 h.

PMID- 29638069
TI  - ASSESSMENT OF GUAR AND XANTHAN GUM BASED FLOATING DRUG DELIVERY SYSTEM CONTAINING
      MEFENAMIC ACID.
AB  - We aimed to assess guar and xantban gum based floating drug delivery system
      containing mefenamic acid. Floating tablets of nefenamic acid were formulated
      with different concentrations of guar and xanthan gum via wet granulation method.
      The flow properties of granules that is: bulk density, tapped density, flow rate,
      Carr index, Hausner's ratio, compressibility index and angle of repose as well as
      physical parameters of the compressed tablets including: hardness, friability,
      thickness and swelling indices were determined and found to be good. Xanthan gum
      was superior to guar gum in maintaining drug release, but a combination of
      polymers was found to be the best for achieving sustained release up to 12 h due
      to the synergistic effect of both gums. Drug release mechanism was best explained
      by Korsmeyer-Peppas model. Fourier transform infrared spectroscopy (FTIR) and
      differential scanning calorimetry (DSC) studies showed absence of any visible
      interaction. Stability studies at 400C (75% RH) showed that the formulation was
      stable at elevated temperature. It can be concluded that floating tablets can be
      used as a sustained release matrix due to their superior characteristics.

PMID- 29638071
TI  - FORMULATION AND IN VITRO EVALUATION OF ACYCLOVIR LOADED POLYMERIC MICROPARTICLES:
      A SOLUBILITY ENHANCEMENT STUDY.
AB  - Objective of present work was to formulate polymeric microparticles of acyclovir
      using 0-cyclodextrin by solvent evaporation method and kneading technique. Four
      different ratios were fabricated in each case. Sodium lauryl sulfate (4% was
      utilized as intestinal permeation enhancer in this study. Prepared microparticles
      were characterized for micromeritic properties i.e., angle of repose, Hausner's
      ratio, Carr's index, bulk density and tapped density, entrapment efficiency, zeta
      size and zeta potential, Fourier transform infrared spectroscopy, differential
      scanning calorimetry, powder x-ray diffraction, scanning electron microscopy,
      transmission electron microscopy, optical microscopy and permeability studies
      across chicken intestine. Kinetic models: zero order, first order, Higuchi and
      Korsmeyer Peppas were applied on release data. Based upon the results of
      entrapment efficiency (81.25% and 74.50%), product yield (92.50% and 85.50%),
      permeability (85.18% and 82.05%), x-ray diffraction (amorphous nature), and
      solubility etc., (1 : 2) drug-polymer ratio was declared the best. Moreover,
      solid dispersions (1 : 2) had shown promising results. A new potential approach
      for solubility, bioavailability and permeability enhancement of acyclovir and
      other BCS class IV drugs was successfully established.

PMID- 29638070
TI  - STUDIES OF THE CRYSTALLINE FORM OF CEFUROXIME AXETIL: IMPLICATIONS FOR ITS
      COMPATIBILITY WITH EXCIPIENTS.
AB  - Amorphous and crystalline forms of cefuroxime axetil were identified and
      characterized using DSC, XRPD, SEM, FT-IR and Raman spectroscopy. Based on the
      results of chromatographic studies, changes in the kinetic mechanism and rate of
      degradation of the crystalline form of cefuroxime axetil in binary systems with
      excipients were also evaluated. The findings suggest that the mechanism of
      degradation of cefuroxime axetil in such systems depends on two factors: the
      applied excipient and storage conditions. Cefuroxime axetil in combination with
      magnesium stearate, croscarmellose sodium and crospovidone, microcrystalline
      cellulose, aerosil is decomposed according to the first-order reaction model in
      dry air as well as at an increased relative air humidity, which may be associated
      with non-catalytic interactions between the active pharmaceutical ingredient and
      the excipients. However, in the presence of mannitol, under elevated humidity
      conditions (RH - 76%), the degradation of cefuroxime axetil follows the
      autocatalytic model. According to ESP maps, computed binding energies and HOMO -
      LUMO gaps, differences of degradation curves between cefuroxime axetil - mannitol
      and other investigated systems were explained. This study of the polymorphic
      transformation of the crystalline form of cefuroxime axetil and its binary
      systems with excipients after exposure to increased temperature and humidity
      indicated a conversion towards the amorphous form or the coexistence of both
      forms.

PMID- 29638072
TI  - OPTIMIZATION OF FUROSEMIDE LIQUISOLID TABLETS PREPARATION PROCESS LEADING TO
      THEIR MASS AND SIZE REDUCTION.
AB  - The great number of drug substances currently used in solid oral dosage forms is
      characterized by poor water solubility. Therefore, various methods of dissolution
      rate enhancement are an important topic of research interest in modem drug
      technology. The purpose of this study was to enhance the furosemide dissolution
      rate from liquisolid tablets while maintaining an acceptable size and mass. Two
      types of dibasic calcium phosphate (Fujicalin(r)/Emcompress(r)) and
      microcrystalline cellulose (Vivapur(r) 102/Vivapur(r) 12) were used as carriers
      and magnesium aluminometasilicate (Neusilin(r) US2) was used as a coating
      material. The flowable liquid retention potential for those excipients was tested
      by measuring the angle of slide. To evaluate the impact of used excipients on
      tablet properties fourteen tablet formulations were prepared. It was found that
      LS2 tablets containing spherically granulated dibasic calcium phosphate and
      magnesium aluminometasilicate exhibit the best dissolution profile and mechanical
      properties while tablets composed only with Neusilin(r) US2 was characterized by
      the smallest size and mass with preserved good mechanical properties and
      furosemide dissolution.

PMID- 29638073
TI  - LEVEL A IN VITRO-IN-IVO CORRELATION DEVELOPMENT AND VALIDA- TION FOR TRAMADOL
      HYDROCHLORIDE FORMULATIONS.
AB  - The objective of this article is to develop and validate the level A in vitro-in
      vivo correlation (IVIVC) for three different formulations of tramadol
      hydrochloride. The formulations included were Tramazac(r) (Ml, conventional
      tablet) and TRD CONTIN(r) (M2, sustained release tablet), and a new controlled
      release tablet prepared on the basis of osmotic technology (formulation IVB). To
      develop level A IVIVC, in vivo data were deconvoluted into absorption data by
      using Wagner-Nelson equation. The absorption data (percent drug absorbed) was
      plotted against percent drug dissolved keeping the former along x-axis and the
      later along y-axis. The highest determination coefficient (R2 = 0.9278) of the
      level A IVIVC was observed for formulation MI, and then for M2 (R2 = 0.9046) and
      IVB (R2 = 0.8796). Additionally, plasma drug levels were approximated from in
      vitio dissolution data using convolution approach to calculate the prediction
      error (%), which was found to be < 10%.

PMID- 29638074
TI  - PHYSICAL AND CHEMICAL STABILITY ANALYSIS OF COSMETIC MULTI- PLE EMULSIONS LOADED
      WITH ASCORBYL PALMITATE AND SODIUM ASCORBYL PHOSPHATE SALTS.
AB  - Stability of hydrophilic and lipophilic vitamin C derivatives for quenching
      synergistic antioxidant activities and to treat oxidative related diseases is a
      major issue. This study was aimed to encapsulate hydrophilic and lipophilic
      vitamin C derivatives (ascorbyl palmitate and sodium ascorbyl phosphate) as
      functional ingredients in a newly formulated multiple emulsion of the W//W type
      to attain the synergistic antioxidant effects and the resultant system's long
      term physical and chemical stability. Several multiple emulsions using the same
      concentration of emulsifiers but different concentrations of ascorbyl palmitate
      and sodium ascorbyl phosphate were developed. Three finally selected multiple
      emulsions (ME1, ME2 and ME3) were evaluated for physical stability in terms of
      rheology, microscopy, conductivity, pH, and organoleptic characteristics under
      different storage conditions for 3 months. Chemical stability was determined by
      HPLC on Sykam GmbH HPLC system (Germany), equipped with a variable UV detector.
      Results showed that at accelerated storage conditions all the three multiple
      emulsions had shear thinning behavior of varying shear stress with no influence
      of location of functional ingredients in a carrier system. Conductivity values
      increased and pH values remained within the skin pH range for 3 months.
      Microscopic analysis showed an increase in globule size with the passage of time,
      especially at higher temperatures while decreased at low temperatures.
      Centrifugation test did not cause phase separation till the 45th day, but little
      effects after 2 months. Chemical stability analysis by HPLC at the end of 3
      months showed that ascorbyl palmitate and sodium ascorbyl phosphate were almost
      stable in all multiple emulsions with no influence of their location in a carrier
      system. Multiple emulsions were found a stable carrier for hydrophilic and
      lipophilic vitamin C derivatives to enhance their desired effects. Considering
      that many topical formulations contain simple vitamin C it is suggested that
      present study may contribute to the development of more stable formulations with
      a combination of vitamin C derivatives to enhance their cosmetic benefits.

PMID- 29638075
TI  - EFFECT OF POLYMER AND PLASTICIZER ON THIN POLYMERIC BUCCAL FILMS OF MELOXICAM
      DESIGNED BY USING CENTRAL COMPOSITE ROTATABLE DESIGN.
AB  - Aim of the present work was to design fast dissolving buccal film of meloxicam
      using central composite rotatable design and to evaluate the effects of polymer
      and plasticizer on formulation and characterization of the buccal films.
      Meloxicam was incorporated in film as model drug, HPMC E15 was used as film
      forming agent and polyethylene glycol (PEG) 400 was used as plasticizer. Films
      were fabricated using solvent casting technique. Prepared films were subjected to
      study various evaluation parameters. Dissolution studies were carried out for 30
      min, using phosphate buffer of pH 6.8. Drug-excipients compatibility was studied
      using Fourier transform infra-red spectroscopy (FTIR). X-ray diffractometry (X
      RD) was used to observe the crystalline or amorphous nature of the drug.
      Differential scanning calorimetry was used for thermal analysis of the drug and
      films. Optical microscopy and scanning electron microscopy were used to study the
      surface morphology. Results revealed that apparently the films were of smooth
      surface with uniform mixing of drug and excipients. Folding fortitude was > 100
      in all the formulations. Weight variations were in acceptable range. Moisture
      loss was directly linked with concentration of plasticizer. Although buccal films
      were showing rapid release of the drug but still it was noticed that increasing
      concentration of HPMC E15 was the cause of drug retardation as well as delay in
      the total dissolution time, while PEG 400 was facilitating the drug release from
      the formulated films. Formulation F5 released approximately 100% drug in 5 min.
      All formulations individually showed total dissolving time in the range of 48-120
      s. There were no noticeable interactions between drug and excipients. Finally, it
      was concluded that meloxicam containing films can be optimized using statistical
      tools, and HPMC E15 in combination with PEG 400 as plasticizer can be effectively
      used in the films formulation.

PMID- 29638076
TI  - THE POSOLOGY AND TROUGH CONCENTRATIONS OF DIGOXIN IN ADULT AND ELDERLY PATIENTS.
AB  - Being a narrow therapeutic index drug, digoxin may cause harm if dosed without
      regular measurements of serum levels. Due to various limitations in its dosing,
      different challenges still exist in clinical practice. This study aimed to assess
      digoxin though concentrations after different regimens in adult and elderly
      patients, and to identify predictor variables for the ratio of given dose and
      digoxin trough level. This was prospective open-label study. Digoxin was
      administered per os as 0.125 or 0.25 mg during different continuous and
      interrupted dosage regimens. Study protocol allowed an additional therapy
      according to contemporary guidelines. Digoxin concentrations were determined
      using Abbott AxSYM Digoxin II assay in trough samples (1-3 per patient) after 3-4
      weeks stable regimen. In total, 191 concentrations (104 patients) were analyzed.
      Digoxin weekly dose was in range 0.375-1.75 mg. On average, we observed slightly
      lower digoxin levels in HF patients. Results showed that in patients receiving
      digoxin with interrupted dosage regimen post- pause digoxin level was
      statistically significantly lower than pre-pause (p < 0.05). Based on multi- ple
      linear regression, the ratio of given dose and trough concentration was mainly
      predicted by clearance creatinine, and to lesser extent by patient's ideal body
      weight. Interrupted dosing schedule shows greater variability in drug levels
      comparing to continuous dosing, and it additionally causes difficulties in
      reaching and maintaining steady trough levels between doses. Hence,
      individualization of dosing regimen should be carefully guided based on target
      levels and not solely on clinical signs and symptoms.

PMID- 29638077
TI  - BLOOD COUNT IN PATIENTS WITH MULTIPLE SCLEROSIS TREATED WITH MITOXANTRONE IN
      SHORT TIME OBSERVATION.
AB  - Multiple sclerosis (MS) is an inflammatory, demyelinating disease that affects
      the central nervous system. Etiology of MS is undiscovered but it is assumed that
      both genetic and environmental triggers play an important role in disease
      pathogenesis. Mitoxantrone (MTX) is an antracycline antibiotic that is used in
      oncologic treatment of breast, prostate, liver, ovarian and stomach cancer. MTX
      is also effective in treatment of primary and secondary progressive multiple
      sclerosis and in relapsing - remitting subtype of disease with no reaction for
      other drugs therapy. In treatment of MS drug is given intravenously in a dose of
      12 mg/m2 in three months intervals to maximal dose of 120-140 mg/m2 of body
      surface. MTX treatment can cause transient reduction of leukocyte, erythrocyte
      and thrombocyte number in blood but the most dangerous side effect of MTX
      treatment is therapy related acute leukemia (TRAL). The aim of this study was to
      evaluate influence of MTX treatment on complete blood count in multiple sclerosis
      patients. Seventy two patients with multiple sclerosis treated with mitoxantrone
      from 2002 to 2014 took part in this study. Control group comprised 60 patients
      with multiple sclerosis who weren't given immunomodulatory treatment. In this
      study, amount of leukocytes, erythrocytes and thrombocytes after MTX treatment
      was compared to those before treatment and in control group. Six patients were
      withdrawn from the study because of leucopenia. A decrease of leukocytes,
      erythrocytes and thrombocytes number after MTX treatment was observed in
      comparison to control group and value before treatment. The decrease of
      erythrocytes number after MTX treatment was statistically significant. The most
      frequent side effect of mitoxantrone treatment is transient, asymptomatic
      leucopenia. Therapy related acute leukemia and other life-threatening
      complications weren't observed in the study group.

PMID- 29638078
TI  - PHARMACEUTICAL CARE FORM APPLICATION IN ELDERLY PATIENTS RESEARCH.
AB  - Many patients, especially elderly, very often don't inform family physicians
      about drugs prescribed by other specialist and use a number of preparations to
      self-medicate. These actions may supply negative consequences in recovery process
      and can be significantly reduced through the implementation of a well-run
      pharmaceutical care (PC) in the community pharmacy. Therefore, it is necessary to
      design proper PC documentation, which allows for comprehensive gathering
      information needed to carry out the analysis of relevant factors impacting on the
      prescribed pharmacotherapy effectiveness. The aim of this study was to develop
      the proper documentation to conduct PC in community pharmacy and verification of
      its correctness in the group of elderly patients, who is receiving treatment from
      family physician and additionally at least two specialized doctors. Also an
      assessment of PC implementation validity as a specialized service was presented.
      A study was carried out from January 2014 to June 2015. The research covered 54
      elderly (41.0% men and 59.0% women) in Jarocin (Poland). Pharmacist was filling
      in the designed PC form, which subsequently was analyzed mainly for
      pharmacotherapy problems. The study indicated that 48.1% of patients were
      counselled by at least 3 specialists; 66.7% of patients were treated by
      cardiologist and 55.6% by the ophthalmologist; 75.9% of participants had
      hypertension. 42.6% of the patients used 10 or more pharmaceuticals and 24.1%
      took 8 or 9 drugs. Moreover, 20.4% of participants used drugs irregularly and
      7.4% of them took too low doses of medications. Additionally, during the
      pharmacotherapy analysis, very significant and significant drug-drug interactions
      were noticed (1.1% and 18.4%, respectively). Very significant drug-food
      interactions occurred in 1.4% cases and significant in 3.3% cases. Total number
      of detected interactions were 553. The substantial analysis of participants' data
      allowed for 48 patients selection for pharmaceutical counselling. Six patients
      were involved into the group where PC process was reasonable. These patients
      often used 10 or more drugs (p = 0.0026), discontinued using medication without
      doctor consulting (p = 0.0201) and did not follow up the prescribed
      pharmacotherapy (p = 0.0351). This study provides new data about implementation
      of PC in Poland. The designed PC documentation may be helpful for proper analysis
      of the patient's pharmacotherapy to avoid drug problems and to improve elderly
      patients' quality of life. This project may contribute to PC implementation in
      Polish community pharmacy.

PMID- 29638079
TI  - ROLE OF THE INTERNATIONAL ORGANIZATIONS IN PREVENTING THE COUNTERFEIT MEDICINES
      ENTRY INTO THE WORLD MARKETS.
AB  - 30 years have passed since Conference of Experts on the Rational Use of Drugs was
      held in Nairobi, Kenya, from 25 to 29 November 1985, where the problem of
      counterfeit medicines was mentioned as the international for the first time. The
      problem of counterfeit medicines is not only a major threat to public health and
      national and private economy, but also it is of great interest for key decision
      making actors at the international level. The authors analyzed what has been done
      since that time by international organizations. Combating the counterfeiting of
      medicines cannot be successfully achieved by the health sector alone - World
      Health Organization (WHO), - so the efforts of the other United Nations (UN)
      organizations relevant to counterfeiting were in need and were studied in the
      article: World Intellectual Property Organization (WIPO), World Trade
      Organization (WTO), World Customs Organization (WCO), United Nations Office on
      Drugs and Crime (UNODC), etc. Today WHO is unable to coordinate all their
      activities, so the few existing proposals for establishing a new mechanism of
      international cooperation have been examined. Will the MEDICRIME Convention that
      will enter into force on January 1, 2016 be the start of the new era in the
      combating with the counterfeit medicines? - the authors offered their vision on
      the international developments.

PMID- 29638080
TI  - ADVERSE DRUG REPORTING IN COMMUNITY PHARMACY PRACTICE IN THE POMERANIAN DISTRICT
      IN POLAND.
AB  - The changing role of the modern pharmacies involves reporting adverse drug
      reactions (ADR's). The aim of the study is to investigate the knowledge of
      community pharmacy professional staff (PS) about the new pharmacovigilance (PG)
      legislation and to analyze patients' attitudes towards the community pharmacy
      role in PG across north central region in Poland. Research material was collected
      in a group of pharmacy PS and patients from January 2014 to August 2014 in the
      Pomeranian District. A cross-sectional study was conducted. The research project
      consisted of three single anonymous surveys. Main outcome measure was knowledge
      of PS towards ADRs reporting, attitudes of patients towards ADRs in relation to
      PS in a community pharmacy. Over half of surveyed pharmacists (54.7%) and only
      13% of pharmaceutical technicians know the correct and current definition of ADR.
      PS do not know what kind of ADRs should be reported - only 41% of pharmacists and
      12.1% of technicians presented adequate knowledge. As far as the knowledge of
      where to notify is concerned - it was present in 60.7% of pharmacists and only
      11.2% of pharmaceutical technicians. In most cases pharmacists (72%) know that
      patients can make their own notifications, technicians showed such knowledge only
      in 37.4% of cases. Patients who detect an ADR occurrence often do not transmit
      the information (19% of respondents). However, if they decide to report, they
      mostly talk to physicians (76.6%), and, less frequently (14.6%), to pharmacy PS.
      In the opinion of patients, however, the pharmacy PS (20.3%) are identified as
      sub- jects involved in reporting ADRs and those who can transmit information on
      the ADRs. The results suggest that pharmacists' knowledge of the rules of
      reporting ADRs is superior to that of pharmaceutical technicians. In fact, PS are
      not sufficiently prepared for reporting ADRs. Patients, in turn, do not have
      adequate awareness of reporting the observed ADRs. They, however, associate the
      community pharmacy with PG system, although the extent is unsatisfactory. In this
      regard, a more effective training of PS would be recommended along with tailored
      social campaigns to inform about the PG system in Poland.

PMID- 29638081
TI  - PHYTOCHEMICAL, ANTIMICROBIAL AND ANTIOXIDANT ACTIVITIES OF PTERIS CRETICA L.
      (PTERIDACEAE) EXTRACTS.

PMID- 29638082
TI  - CHEMICAL COMPONENTS AND VARIABILITY OF THE ESSENTIAL OILS ISOLATED FROM
      INFLORESCENCES OF CARDUUS SPP.

PMID- 29638083
TI  - SYNTHESIS AND PHARMACOLOGICAL ACTIVITY OF IMIDAZO[2,1- b][1,3,4]THIADIAZOLE
      DERIVATIVES.

PMID- 29638084
TI  - RELATIVE BIOAVAILABILITY STUDY OF SUCCINIC ACID COCRYSTAL TABLET AND MARKETED
      CONVENTIONAL IMMEDIATE RELEASE TABLET FORMULATION OF CARBAMAZEPINE 200 MG IN
      RABBITS.

PMID- 29638085
TI  - A perspective on paediatric surgical training: opportunities and challenges.
AB  - Globally, the training of paediatric surgeons is facing numerous challenges.
      Exposure to rare and complex index pathology is vital in the training of
      competent paediatric surgeons, but it is this rarity and complexity that creates
      a fundamental challenge to training programmes the world over.

PMID- 29638086
TI  - Can an Enhanced Recovery After Surgery(ERAS) programme improve colorectal cancer
      outcomes in South Africa?
AB  - Colorectal cancer (CRC) is the third most common cancer worldwide and the fourth
      most common cause of cancer related deaths. It is estimated that CRC is amongst
      the top five malignancies in South Africa (SA) with an age standardised incidence
      rate of 10.2 and 6.1 per 100 000 for males and females respectively. The
      incidence is projected to increase in South Africa as a result of ageing, a
      growing population and an increase in prevalence of risk factors.

PMID- 29638087
TI  - Where are general surgeons located in South Africa?
AB  - BACKGROUND: Human resources are the backbone of health-care delivery systems and
      the lack of surgical workforce in developing countries is often the greatest
      challenge to providing surgical care. The workforce availability and composition
      is an important indicator of the strength of the health system. This study aimed
      to analyse the distribution of general surgeons within South Africa. METHOD: A
      descriptive analysis of the general surgical workforce in South Africa was
      performed. The total number of specialist and non-specialist general surgeons
      working in the public sector in South Africa was documented between the periods
      from the 1 October 2014 until 31 December 2014. RESULTS: There were significant
      disparities in the number and distribution of general surgeons in South Africa.
      There were 1.78 specialist general surgeons per 100 000, of which 0.69 per 100
      000 specialist general surgeons were working in the public sector. There were
      2.90 non-specialist general surgeons per 100 000. There were 6 specialist general
      surgeons per 100 000 insured population working in the private sector, which is
      comparable with the United States (US). Urban provinces such as Gauteng, the
      Western Cape and KwaZulu-Natal had the largest number of specialist general
      surgeons per 100 000. These areas had the largest number of medical aid
      beneficiaries and nearly 60% of specialist general surgeons were estimated to
      work exclusively in the private sector. CONCLUSION: There was a major shortage of
      surgical providers in South Africa, and in particular the public sector.

PMID- 29638088
TI  - Malignant and pre-malignant oesophageal pathology in a South African teaching
      hospital.
AB  - BACKGROUND: South Africa (SA) has one of the highest global incidences of
      squamous cell carcinoma of the oesophagus (SCC). A decreasing incidence of
      oesophageal SCC in SA has been suggested. The study aimed to assess whether the
      incidence of these malignant histopathological subtypes has changed in this
      setting. METHOD: A retrospective review of histopathological reports on pre
      malignant and malignant oesophageal lesions over three time periods (TP), namely:
      2003-4 (TP1), 2008-9 (TP2) and 2013-14 (TP3) was carried out at Inkosi Albert
      Luthuli Central Hospital, Durban, South Africa. RESULTS: A total of 1341 specimen
      reports were retrieved. TP1-3 consisted of 514 (39.3%), 320 (24.5%) and 474
      (36.2%) patients respectively. Six hundred and forty-nine patients were male
      (48.3%), 642 were female (47.8%) and 50 were not specified. i.e. a sex ratio of
      1.01:1. The mean age was 60.8 (+/- 11.8). There were 1197 Black patients (91.5%),
      66 Asian (5.1%), 25 White (1.9%), 9 mixed ancestry (0.7%), and 11 of unknown race
      (0.8%). SCC was the most common cancer 1098 (89.1%) followed by adenocarcinoma
      (AC) 69 (5.6%). The ratio of SCC to AC remained fairly consistent over the total
      time period. Seventy-four oesophageal resections were performed with a yearly
      average resection rate of only 5.6%. CONCLUSION: SCC is still the most prevalent
      oesophageal cancer (OC) without an increase in the ratio of AC to SCC. The
      diagnosis of squamous cell dysplasia is concordant with previously cited rates.
      Barrett's oesophagitis remains uncommon. Resection rates for OC are low but
      similar to other South African referring centers.

PMID- 29638089
TI  - Pattern of mismatch repair protein loss and its clinicopathological correlation
      in colorectal cancer in North India.
AB  - BACKGROUND: To determine the mismatch repair (MMR) protein loss in colorectal
      cancer (CRC) in north Indian patients and its clinicopathological correlation.
      METHOD: A prospective study on patients with colorectal cancer from a tertiary
      level hospital conducted between May 2014 and June 2015. MMR protein loss was
      determined using immunohistochemistry for MLH1, MSH2, PMS2 and MSH6. RESULTS: 52
      patients (38 male and 14 females) of CRC, with median age of 52.5 years who
      underwent resection form the study group. 18 (35%) patients were < 50 years of
      age. Family history of malignancy was present in 3 (6 %) patients. A total of 15
      (29%) patients had loss of MMR protein of which 7 (46%) were < 50 years. Most
      common MMR loss was combined loss of MSH2 + MSH6 [6 (11.5%)] followed by isolated
      loss of PMS2 [5 (9.6%)]. MMR protein loss was more frequent in patients with
      right side colon cancer [12 (42%)] compared to left [3 (13%)] (p = 0.033). MMR
      protein loss was seen in 11 (34%) out of 32 patients fulfilling the revised
      Bethesda criteria compared to 4 (20%) out of 20 patients who did not fulfil the
      criteria (p = 0.352). CONCLUSION: This study demonstrates high frequency of MMR
      protein loss in colorectal cancer in north Indian patients which was more common
      in right colon cancer. Many patients having MMR protein loss do not satisfy the
      revised Bethesda criteria and would have been missed if selective testing was
      done. Further research and larger studies are required to validate these findings
      and develop India specific clinical criteria.

PMID- 29638090
TI  - Distal malignant biliary obstruction: a prospective randomised trial comparing
      plastic and uncovered self-expanding metal stents in the palliation of
      symptomatic jaundice.
AB  - BACKGROUND: The aim of this study was to determine the safety and clinical
      effectiveness of 10Fr plastic biliary stents compared to uncovered self-expanding
      metal stents (SEMS) for palliative treatment of patients with inoperable extra
      hepatic malignant biliary obstruction in a public hospital in South Africa.
      METHOD: From January 2009 to December 2013, 40 patients who were admitted to a
      tertiary academic centre because of distal malignant biliary obstruction were
      enrolled in a prospective randomized study. Patients were randomly assigned to
      receive an uncovered SEMS or a plastic stent deployed through the biliary
      stricture during endoscopic retrograde cholangiopancreatography (ERCP). RESULTS:
      Patient survival time in the two groups did not differ significantly (median:
      SEMS - 114 days; plastic - 107 days). Stent failure was more common in the
      plastic stent group (7/19 vs. 1/21). The results became significant after 6
      months of follow-up. There was no significant difference between the two groups
      in the incidence of serious adverse events. CONCLUSION: SEMS had a longer
      duration of patency than plastic stents, which recommends their use in the
      palliative treatment of patients with biliary obstruction due to distal malignant
      biliary obstruction.

PMID- 29638091
TI  - Five year review of open radical nephrectomies at a regional hospital in South
      Africa: room for improvement.
AB  - BACKGROUND: To review the presentation and outcomes of patients undergoing open
      radical nephrectomy (ORN) for renal cell carcinoma (RCC) at a regional hospital
      in KwaZulu-Natal, South Africa. METHOD: A retrospective chart review was
      performed of patients having undergone nephrectomy at St Aidan's hospital between
      2010 and 2015, focusing on those with RCC. Demographic, operative, histopathology
      and outcomes data were collected. RESULTS: Fifty-two patients (51%) had ORN for
      suspected malignant disease. Forty-one RCCs were found including one incidental
      finding at simple nephrectomy. Data was insufficient to assess risk factors for
      RCC. HIV positive patients tended to present earlier (45 vs. 53 years). The mean
      tumour size was 10 cm and organ confined disease was present in 73.2% of
      patients. Only 11 patients (26.8%) had pT1 disease. The high-grade complication
      rate was 9.8%, in-hospital mortality rate 4.9% and transfusion rate 51.2%. The
      median operating time was 1h 50min and length of hospital stay 13 days.
      CONCLUSION: Open radical nephrectomy is the standard surgical treatment for RCC
      at regional level in South Africa. Patients tend to present at a younger age,
      particularly if HIV positive, and with large tumours. Further research into risk
      factors for RCC in the South African population is needed. There are high
      complication and transfusion rates in patients undergoing ORN. Review of
      accessibility of blood at St Aidan's hospital and revision of the transfusion
      protocol is suggested. A followup study to assess the feasibility and cost
      effectiveness of laparoscopic nephrectomy in the resource-constrained South
      African environment is necessary.

PMID- 29638092
TI  - [Dissections of the supraaortic arteries].
AB  - Dissection of the cervical and intracranial vasculature is a rare but important
      cause of ischaemic stroke especially in young adults. In the majority of cases it
      affects the extracranial vessels, mostly the internal carotid artery. It might be
      categorized as spontaneous or traumatic, causing diverse clinical symptoms.
      Dissection might lead to ipsilateral stroke mainly by artery-to-artery
      embolisation. Due to its relative rarity compared to the classic ischaemic stroke
      of the elderly, there are much less clinically relevant information for the
      clinician to rely on. Several large, randomised, multicentered, prospective
      studies and some smaller, retrospective analyses have been published recently
      concerning the genetic background, epidemiology, acute care and secondary
      prevention of supraaortic arterial dissection which helps the neurologist to
      provide evidence-based care for his patient. Our aim is to give a short, up-to
      date overview of arterial dissections with two case reports.

PMID- 29638093
TI  - [Eating disorders and pregnancy - a review of literature].
AB  - Eating disorders are psychosomatic disorders affecting primarily women, and
      influence reproductive functions as well. They have an impact on ovarial cyclem
      fertility, course of pregnancy, process of delivery, post partum period.
      Moreover, some data show that they can influence the adult health status.
      Extensive research from the last three decades call the attention to the fact
      that besides the classical eating disorders (anorexia nervosa and bulimia
      nervosa) the newer types (e.g., orthorexia nervosa), and subclinical disorders
      also occur in a subgroup of pregnant women. For this reason it is of key
      importance that the personnel working in the territory of obstetrics and
      gynecology have a solid knowledge about the symptoms, screening and therapeutical
      opportunities, and outcome of these disorders. The review summarizes the recent
      research data about the relationship of eating disorders and pregnancy.

PMID- 29638094
TI  - [Functional magnetic resonance imaging studies in pain research].
AB  - Functional imaging studies opened a new way to understand the neural activity
      underlying pain perception and the pathomechanism of chronic pain syndromes. In
      the last twenty years several results of functional magnetic resonance imaging
      (fMRI) studies have been published about examining the different aspects of
      complex pain experience. The aim of these studies is to understand the
      functioning of the pain control system, the so-called pain matrix, activated by
      acute nociceptive stimulus. Another important field of pain research is the
      investigation of neuronal processes underlying chronic pain, since the
      pathomechanism of this is still unclear. Our review aims to provide insight into
      the methods of pain research using fMRI and the achievements of the last few
      years.

PMID- 29638095
TI  - Stress-induced corticosterone rise maintain gastric mucosal integrity in rats.
AB  - Background and purpose: To investigate contribution of glucocorticoids to the
      maintenance of gastric mucosal integrity during stress we predominantly used
      ulcerogenic stress models. Using these models we demonstrated that
      glucocorticoids released in response to the ulcerogenic stimuli attenuated their
      harmful action on the gastric mucosa. In the present study we hypothesized that
      mild stressors does not damage the gastric mucosa due to gastroprotective action
      of glucocorticoids released in response to these stressors. Methods: To verify
      the hypothesis the effects of normally non-ulcerogenic mild stimuli (15-30 min
      cold-restraint) on the gastric mucosal integrity have been studied under the
      circumstances of inhibition of the hypothalamic-pituitaryadrenocortical axis in
      rats. The hypothalamic-pituitary-adrenocortical axis was inhibited by: 1) fast
      inhibitory action of metyrapone, inhibitor glucocorticoid synthesis; 2) fast
      inhibitory action of NBI 27914, the selective antagonist of cortricotropin-
      releasing factor receptor type 1; 3) delayed inhibitory action of a single
      pharmacological dose of cortisol injected one week before the onset of stress
      stimulus. Results: Each of these pretreatments significantly decreased 15-30 min
      cold-restraint-produced corticosterone levels: 37.2+/-1 vs 22.5+/-1.2 (p<0.05)
      after metyrapone; 52.1+/-0.9 vs 41.4+/-1 (p<0.05) after NBI, and 64.2+/-4.2 vs
      16.7+/-1.5 (p<0.05) after cortisol pretreatment. The inhibition of stress-induced
      corticosterone rise resulted in an ap - pearance of gastric lesions after the
      onset of these mild stressors in rats. Conclusion: The results suggest that in
      rats with inhibited stress-induced corticosterone rise normally non-ulcerogenic
      stimuli are transformed into ulcerogenic ones and confirm the hypothesis. The
      findings further support for the point of view that glucocorticoids released
      during acute stress are gastroprotective factors.

PMID- 29638096
TI  - Cerebral vasomotor reactivity in fibromyalgia patients and its relationship to
      central neuropathic pain.
AB  - Background - Cerebral vasomotor reactivity, defined as the cerebral vasculature
      response to hypoxia, is not wellunderstood in fibromyalgia (FM) patients. This
      study investigated the difference in the cerebrovascular reactivity (i.e.,
      responsiveness to hypercapnia was evaluated by use of breath- holding index) to
      the breath-holding index (BHI) between patients with fibromyalgia and a group of
      normal controls. Methods - The study included 40 FM patients and 40 healthy
      subjects. Cerebrovascular reactivity was evaluated using the BHI, which is a
      nonaggressive, well-tolerated, real-time, reproducible screening method to study
      cerebral haemodynamics. Insonation depth and basal velocity were symmetrical and
      not significantly different between the two groups (p>0.05). All patients
      completed the Revised Fibromyalgia Impact Questionnaire (FIQR), Hospital Anxiety
      and Depression Scale (HADS), visual analogue scale (VAS), and the somatization
      subscale of the SCL-90-R symptom checklist. Results - The BHI ranged from 0.30 to
      2.20 (mean 1.11+/-0.45) in the FM patients and 1.10 to 2.80 (mean 1.90+/-0.35) in
      the control group (p<0.001). Disease duration and right BHIaverage and left
      BHIaverage values exhibited a significant negative correlation (r=-0.877;
      p<0.001, r=-0.842; p<0.001, respectively). As pain and fatigue scores increased,
      the right BHIaverage and left BHIaverage values decreased (r=-0.431; p=0.005, r=
      0.544; p<0.001, r=-0.341; p=0.031, r=-0.644; p<0.001, respectively). Conclusions 
      BHI values showed that cerebrovascular reactivity in FM patients decreased in
      comparison to healthy individuals. BHI decreased as disease duration and severity
      increased. Cerebrovascular reactivity decreased in FM patients, and this
      phenomenon should be accepted as an abnormality. Additionally, this outcome may
      have been the result of a mechanism responsible for central neuropathic pain.

PMID- 29638098
TI  - Adult attachment and parental bonding in irritable bowel syndrome and in panic
      disorder - Implications for psychotherapy.
AB  - Background and purpose: Attachment theory provides an integrative perspective
      about the interplay between cognitive, affective, behavioral and interpersonal
      processes and is relevant for understanding irritable bowel syndrome (IBS) and
      panic disorder (PD). The aim of the present study was to examine the adult
      attachment style and parental bonding of IBS and PD patients. Methods: In a cross
      sectional questionnaire-based study, 65 PD and 65 IBS patients with clinical
      diagnosis participated. Measures were Attachment Style Questionnaire, Experiences
      in Close Relationships Scale - Revised, and Parental Bonding Instrument. Results:
      The frequencies of insecure attachment (80.0% vs. 63.1%) and paternal neglect
      (35.4% vs. 16.9%) were higher in IBS than in PD (chi2 (1)=4.571, p=0.033, and
      chi2 (3)=7.831, p=0.050, respectively). The frequency of secure attachment was
      significantly higher for optimal paternal bonding than with suboptimal paternal
      bonding (75.0% vs. 21.9%, chi2 (1)=19.408, p<0.001). According to the results of
      multiple binary logistic analysis, optimal paternal bonding predicted secure
      attachment after adjusting for the background variables (OR=9.26, p=0.001).
      Conclusion: A high frequency of insecure attachment was present in both groups,
      especially in IBS. With regard to maternal bonding, IBS and PD groups showed
      similar patterns, while an apparent difference was observed for paternal bonding.
      These highlighted the developmental similarities of these two, symptomatically
      different disorders. While optimal maternal bonding did not predict adult
      attachment security, paternal bonding did thus replete with therapeutic
      implications. Attachment functions, like responsiveness, attunement and affection
      modulation were apparent in the psychotherapist-patient relationship as well.

PMID- 29638097
TI  - Frequency and types of headaches in patients with metabolic syndrome.
AB  - Background and purpose: Metabolic Syndrome (MetS) and headaches are common public
      health problems in whole world. The relationship between headaches and the MetS
      isn't understood clearly. Purpose - The aim of this study is to determine the
      prevalence and types of headaches, and evaluate the relationship between headache
      characteristics and clinical and laboratory parameters analyzed in patients
      diagnosed with MetS. Methods: Of the patients diagnosed with MetS in
      Endocrinology outpatient clinics between July 2011 and July 2012, 202 patients
      were included in the study. Hemoglobin, fasting blood glucose (FBG), total
      cholesterol, triglyceride, HDL and LDL cholesterol, thyroid function tests and
      HbA1c values of all patients were recorded. Beck Depression Inventory (BDI) and
      Beck Anxiety Inventory (BAI) were applied to all patients. The headache severity
      was assessed by Visual Analog Scale (VAS). Results: The prevalence of headache in
      patients with MetS was found to be 61.4%. The incidence of headache was higher in
      female patients (F: 86.4%, M: 13.6%). The distribution of the subtypes of
      headaches was as follows: Episodic Tension-Type Headaches (ETTH) 24.8%, Episodic
      Migraine 14.4%, Chronic Tension-Type Headaches (CTTH) 11.3%, Episodic Tension
      Type Headaches (ETTH) and Episodic Migraine 7.9%, and other types of headaches
      (Cervicogenic Headache and Cluster Headache) 3%. No statistically significant
      relationship was found between headache and non-headache groups in terms of body
      mass index, waist circumference, and the laboratory parameters (p>0.05). The mean
      BDI and BAI scores were higher in the headache group (p<0.001 and p<0.001). No
      significant difference was found between the mean MIDAS scores in the subtypes of
      headaches (p=0.35). In the headache group, there was a significant relationship
      only between triglyceride levels and attack frequency, duration and severity.
      Conclusion: Prevalence of headache in patients with MetS was 61.4%. The incidence
      of subtypes of headaches was similar to those in the general population. A
      relationship was found between triglyceride levels and attack frequency and
      severity. The result may be important to draw attention to the evaluation of
      triglyceride levels for reducing the frequency and severity of attacks in
      patients with headaches.

PMID- 29638099
TI  - [Our experience with the use of Active-C cervical prosthesis].
AB  - Background and purpose: The most widely used surgical procedure in the treatment
      of cervical spine disc hernias have been the anterior cervical discectomy and
      fusion for decades. The usage of cervical disc prostheses enabled us to preserve
      the movements of the affected segments, hereby reducing the overexertion of the
      adjacent vertebrae and discs. Our goal is to follow our patients operated with
      Active-C prosthesis (which is used in the Institute since 2010) to gather
      information about the change of their complaints and about the functioning and
      unwanted negative effects of the prostheses. Question - Is the usage of Active-C
      prosthesis an efficient procedure? Methods: Between 2010 and 2013, performing the
      survey of neurological conditions and functional X-ray examinations. We measured
      the complaints of the patients using the Visual Analogue Scale, Neck Disability
      Index and Cervical Spine Outcomes Questionnaire. The control group consisted of
      patients who were operated in one segment using the fusion technique. Results: In
      the study group according to the Neck Disability Index scale after 18 months,
      seven patients had no complaints, while twelve persons reported mild and the
      remaining six moderate complaints. In the control group, moderate complaints were
      present in four patients, while twelve patients reported mild complaints. The
      other eight persons showed no complaints. According to the results of the Visual
      Analogue Scale in the group of prosthesis, the degree of referred pain decreased
      from 8.6 to 1.84 one and a half years after the surgery. A decrease was
      observable in the case of axial pain too, from 6.6 down to 1.92 (p<0.01). In case
      of three from the twenty-five patients there was no sign of movement in the level
      of the prosthesis. Conclusion: According to the present short- and mediumterm
      studies, the usage of the cervical disc prosthesis can be considered as an
      efficient procedure, but at the same time the advantages can only be determined
      in the long run, therefore further following and studies are required.

PMID- 29638100
TI  - Restless Leg Syndrome/Willis-Ekbom disease in women with iron deficiency anemia.
AB  - Background and purpose: Restless Leg Syndrome (RLS) also known as Willis-Ekbom
      Disease (WED) is a common condition associated with reduced quality of life and
      other medical conditions, particularly cardiovascular diseases. Despite its
      common occurrence, it is widely underdiagnosed and undertreated. Therefore,
      identification of high-risk individuals for RLS/WED bears diagnostic and
      therapeutic significance. Iron deficiency anemia has a role in the
      pathophysiology of RLS/WED and both conditions have been reported to occur higher
      in females. In this study, the frequency of RLS/WED among women diagnosed with
      iron deficiency anemia was examined as well as laboratory variables that could
      guide the clinician in the diagnosis of RLS/WED. Methods: A total of 51 women
      attending to the department of internal medicine with complaints of fatigue and
      tiredness and diagnosed as having iron deficiency anemia were evaluated using the
      International Restless Leg Syndrome Study Group (IRLSSG) diagnostic criteria for
      RLS. Laboratory variables were recorded. The severity of RLS/WED was assessed
      using the RLS rating scale in patients diagnosed with RLS/WED. Results: RLS/WED
      was diagnosed in 41.1% of the women with iron deficiency anemia. There were no
      significant differences between women with or without RLS /WED in terms of
      laboratory variables. Also, no correlations were observed between disease
      severity and laboratory variables. Conclusion: There is an 8 to 10-fold increase
      in the incidence of RLS/WED among women with iron deficiency anemia as compared
      to general population. Therefore, a possible diagnosis of RLS/WED should be kept
      in mind in all women with iron deficiency anemia.

PMID- 29638101
TI  - [Operation - rehabilitation - employment].
AB  - In this article we would like to bring the attention to the importance of early
      rehabilitation, coordinated operation of different subdivisions of rehabilitation
      and the expanding opportunities after medical care through following a 38- year
      old female patient's case who was operated 6 years ago with anaplasticus
      oligodendroglioma. We find it important that the experts working on the field of
      health care, social services or labour should be aware of the possibilities of
      rehabilitation of their patients from the capability assessment, through its
      development until their placement in integrated labour market. It is important,
      that even during the medical care both the client and their relatives receive
      proper information.

PMID- 29638102
TI  - Hand-foot-genital syndrome - analysis of two cases.
AB  - Hand-food-genital syndrome (HFGS) is a rare genetic condition. This report
      describes the cases of two patients, aged 33 and 15, presenting related somatic
      abnormalities. HFGS stems from an autosomal anomaly linked to the HOXA 13 gene.
      Therapeutic procedures are discussed in order to identify the best treatment
      approach to the patients, as well as possible conditioning genetic anomalies.

PMID- 29638103
TI  - Caregivers and Families of Critically Ill Patients.

PMID- 29638104
TI  - Precise Nanoscale Measurements with Scanning Probe Microscopy (SPM): A Review.
AB  - For many of measurements, it is important to know the interaction of the
      measuring device with the artefact being measured in order to determine the
      accurate magnitude of the quantity. Mechanical, electrical, magnetic, optical and
      chemical properties of materials are also important parameters that need to be
      quantified at the micro and nanometre level. In this review, we introduce
      principles of scanning probe microscopy (SPM) and related technique; and also
      give the advance in nano-/micro-electro-mechanical systems (NEMS/MEMS)
      measurements using SPM. Firstly, we described state of the SPMs, their essential
      components and recent developments in this field. Then, conventional as well as
      advanced instruments have been addressed, measurement requirements discussed for
      measurement and fabrication. Finally, many different applications of SPMs in
      micro/nano electronics fields such as high resolution imaging, micro/nano
      electronics, Metrology and manipulation and spectroscopy have been described in
      the article. Nevertheless, SPMs are advancing, supported by user-friendly and
      application-oriented features, improved software and combination with other
      instruments high precision measurement fields.

PMID- 29638105
TI  - Applications of Nanomaterials in Dental Science: A Review.
AB  - Nanotechnology has revolutionized health care industry in a large scale and its
      applications are a boon to modern medicine and dental science. It is expected to
      pervade and further revolutionize the art and science of dentistry and may well
      have important applications spanning all the aspects of oral diseases, diagnosis,
      prevention and treatment. Materials science in dentistry has embraced the
      technology to produce nanomaterials that are being used in caries inhibitors,
      antimicrobial resins, hard tissue remineralizing agents, targeted drug delivery,
      scaffolds, bio-membranes, nanocrystalline hydroxyl apatite, restorative cements,
      adhesion promoters and boosters, bioactive glass, tissue conditioners, reinforced
      methacrylate resins, root canal disinfectants, friction free orthodontic arch
      wires and nano composites life. These upcoming technologies have potential to
      bring about significant benefits in the form of improvement in dental science and
      to society. The present review presents the latest recent developments in this
      interdisciplinary field bridging nanotechnology and dental science.

PMID- 29638106
TI  - Enhanced Electrochemical and Thermal Transport Properties of Graphene/MoS2
      Heterostructures for Energy Storage: Insights from Multiscale Modeling.
AB  - Graphene has been combined with molybdenum disulfide (MoS2) to ameliorate the
      poor cycling stability and rate performance of MoS2 in lithium ion batteries, yet
      the underlying mechanisms remain less explored. Here, we develop multiscale
      modeling to investigate the enhanced electrochemical and thermal transport
      properties of graphene/MoS2 heterostructures (GM-Hs) with a complex morphology.
      The calculated electronic structures demonstrate the greatly improved electrical
      conductivity of GM-Hs compared to MoS2. Increasing the graphene layers in GM-Hs
      not only improves the electrical conductivity but also stabilizes the
      intercalated Li atoms in GM-Hs. It is also found that GM-Hs with three graphene
      layers could achieve and maintain a high thermal conductivity of 85.5 W/(m.K) at
      a large temperature range (100-500 K), nearly 6 times that of pure MoS2 [~15
      W/(m.K)], which may accelerate the heat conduction from electrodes to the
      ambient. Our quantitative findings may shed light on the enhanced battery
      performances of various graphene/transition-metal chalcogenide composites in
      energy storage devices.

PMID- 29638107
TI  - High Catalytic Performance of a CeO2-Supported Ni Catalyst for Hydrogenation of
      Nitroarenes, Fabricated via Coordination-Assisted Strategy.
AB  - A family of two-dimensional salen-type lanthanide complexes was synthesized
      through a facile solution diffusion method. The two-dimensional lanthanide
      complexes were characterized by single-crystal X-ray diffraction (SCXRD) and X
      ray photoelectron spectroscopy (XPS) analytical techniques. The SCXRD and XPS
      analyses reveal that the obtained two-dimensional structures are rich in
      uncoordinated imine (-CH?N-) groups located on the skeleton of the salen-type
      organic ligand, which retain strong coordination ability with metal ions. On the
      basis of this unique feature, a highly dispersed CeO2-supported Ni catalyst
      (Ni/CeO2-CAS) with highly strong metal-support interaction was first synthesized
      via a coordination-assisted synthesis (CAS) method, which exhibits a much better
      catalytic activity in the hydrogenation of nitrobenzene than the traditional
      Ni/CeO2-IWI catalyst prepared by incipient wetness impregnation (IWI). The origin
      of the improved catalytic activity of Ni/CeO2-CAS as well as the role of Ni@Ce
      H2salen was revealed by using diverse characterizations. On the basis of the
      comparative characterization results, the superior catalytic performance of
      Ni/CeO2-CAS to Ni/CeO2-IWI could have resulted from the smaller and highly
      dispersed Ni nanoparticulates, the intensified Ni-CeO2 interaction, the enhanced
      NiO reducibility, and the higher concentration of oxygen vacancies, favoring the
      H2 dissociation and adsorption of the nitrobenzene reactant. The Ni/CeO2-CAS
      catalyst also exhibits high catalytic performance for reduction of diverse
      nitroarenes to their corresponding functionalized arylamines. We anticipated that
      this coordination-assisted strategy may provide a new way for preparing other
      highly oxide-supported catalysts with potential applications in various catalytic
      reactions.

PMID- 29638108
TI  - Editable TiO2 Nanomaterial-Modified Paper in Situ for Highly Efficient Detection
      of Carcinoembryonic Antigen by Photoelectrochemical Method.
AB  - In this work, a versatile photoelectrochemical paper-based sensor based on N
      carbon dots/TiO2-Pt-modified paper in situ is developed for sensitive detection
      of carcinoembryonic antigen (CEA) in clinical serum samples. Interconnected
      cellulose fibers on paper provide a porous, 3D, and flexible substrate for
      photoelectrochemical sensing. In situ modification of N-carbon dots/TiO2-Pt with
      editable structures on paper significantly increases the conductivity, widens the
      adsorption range, and enhances the photoelectrochemical ability, which enables
      the higher sensitivity and flexibility compared with traditional rigid sensors.
      On the basis of this novel protocol, a miniaturized and portable origami device
      realizes the CEA determination with a low detection limit of 1.0 pg mL-1 and a
      wide linear range from 0.002 to 200 ng mL-1. Thanks to the good biocompatibility,
      the paper-based device provides a new avenue for the detection of CEA on the cell
      surface which is promising for portable diagnostics in early tumor warning.

PMID- 29638109
TI  - CuBi2O4 Prepared by the Polymerized Complex Method for Gas-Sensing Applications.
AB  - Multicomponent oxides can be extensively explored as alternative gas-sensing
      materials to binary oxides with their structural and compositional versatilities.
      In this work, the gas-sensing properties of CuBi2O4 have been investigated toward
      various reducing gases (C2H5OH, NH3, H2, CO, and H2S) and oxidizing gas (NO2) for
      the first time. For this, the powder synthesis has been developed using the
      polymerized complex method (Pechini method) to obtain a single-phase
      polycrystalline CuBi2O4. The defect, optical, and electronic properties in the
      prepared CuBi2O4 powder were modulated by varying the calcination temperature
      from 500 to 700  degrees C. Noticeably, a high concentration of Cu+-oxygen
      vacancy ([Formula: see text]) defect complexes and isolated Cu2+ ion clusters was
      found in the 500  degrees C-calcined CuBi2O4, where they were removed through air
      calcination at higher temperatures (up to 700  degrees C) while making the
      compound more stoichiometric. The change in the intrinsic defect concentration
      with the calcination temperature led to the variation of the electronic band gap
      energy and hole concentration in CuBi2O4 with the polaronic hopping conduction
      (activation energy = 0.43 eV). The CuBi2O4 sensor with 500  degrees C-calcined
      powder showed the highest gas responses (specifically, 10.4 toward 1000 ppm
      C2H5OH at the operating temperature of 400  degrees C) with the highest defect
      concentration. As a result, the gas-sensing characteristics of CuBi2O4 are found
      to be dominantly affected by the intrinsic defect concentration, which is
      controlled by the calcination temperature. Toward reducing H2S and oxidizing NO2
      gases, the multiple reactions arising simultaneously on the surface of the
      CuBi2O4 sensor govern its response behavior, depending on the gas concentration
      and the operating temperature. We believe that this work can be a cornerstone for
      understanding the effect of chemical defect on the gas-sensing characteristics in
      multicomponent oxides.

PMID- 29638110
TI  - Ultrastable Photoelectrodes for Solar Water Splitting Based on Organic Metal
      Halide Perovskite Fabricated by Lift-Off Process.
AB  - Herein, we report an integrated photoelectrolysis of water employing organic
      metal halide (OMH) perovskite material. As generic OMH perovskite material and
      device architecture are highly susceptible to degradation by aqueous
      electrolytes, we have developed a versatile mold-cast and lift-off process to
      fabricate and assemble multipurpose metal encapsulation onto perovskite devices.
      With the metal encapsulation effectively protecting the perovskite cell and also
      functioning as electrocatalyst, the high-performance perovskite photoelectrodes
      exhibit high photovoltage and photocurrent that are effectively inherited from
      the original solid-state solar cell. More importantly, thus-fabricated perovskite
      photoelectrode demonstrates record-long unprecedented stability even at highly
      oxidizing potential in strong alkaline electrolyte. We expect that this versatile
      lift-off process can be adapted in a wide variety of photoelectrochemical devices
      to protect the material surfaces from corroding electrolyte and facilitate
      various electrochemical reactions.

PMID- 29638111
TI  - Conformational Transition of Key Structural Features Involved in Activation of
      ALK Induced by Two Neuroblastoma Mutations and ATP Binding: Insight from
      Accelerated Molecular Dynamics Simulations.
AB  - Deregulated kinase activity of anaplastic lymphoma kinase (ALK) has been observed
      to be implicated in the development of tumor progression. The activation
      mechanism of ALK is proposed to be similar to other receptor tyrosine kinases
      (RTKs), but the distinct static X-ray crystal conformation of ALK suggests its
      unique conformational transition. Herein, we have illustrated the dynamic
      conformational property of wild-type ALK as well as the kinase activation
      equilibrium variation induced by two neuroblastoma mutations (R1275Q and Y1278S)
      and ATP binding by performing enhanced sampling accelerated Molecular Dynamics
      (aMD) simulations. The results suggest that the wild-type ALK is mostly favored
      in the inactive state, whereas the mutations and ATP binding promote a clear
      shift toward the active-like conformation. The R1275Q mutant stabilizes the
      active conformation by rigidifying the alphaC-in conformation. The Y1278S mutant
      promotes activation at the expense of a pi-stacking hydrophobic cluster, which
      plays a critical role in the stabilization of the inactive conformation of native
      ALK. ATP produces a more compact active site and thereby facilitates the
      activation of ALK. Taken together, these findings not only elucidate the diverse
      conformations in different ALKs but can also shed light on new strategies for
      protein engineering and structural-based drug design for ALK.

PMID- 29638112
TI  - Surface-Enhanced Raman Spectroscopy for Bioanalysis: Reliability and Challenges.
AB  - Surface-enhanced Raman spectroscopy (SERS) inherits the rich chemical fingerprint
      information on Raman spectroscopy and gains sensitivity by plasmon-enhanced
      excitation and scattering. In particular, most Raman peaks have a narrow width
      suitable for multiplex analysis, and the measurements can be conveniently made
      under ambient and aqueous conditions. These merits make SERS a very promising
      technique for studying complex biological systems, and SERS has attracted
      increasing interest in biorelated analysis. However, there are still great
      challenges that need to be addressed until it can be widely accepted by the
      biorelated communities, answer interesting biological questions, and solve fatal
      clinical problems. SERS applications in bioanalysis involve the complex
      interactions of plasmonic nanomaterials with biological systems and their
      environments. The reliability becomes the key issue of bioanalytical SERS in
      order to extract meaningful information from SERS data. This review provides a
      comprehensive overview of bioanalytical SERS with the main focus on the
      reliability issue. We first introduce the mechanism of SERS to guide the design
      of reliable SERS experiments with high detection sensitivity. We then introduce
      the current understanding of the interaction of nanomaterials with biological
      systems, mainly living cells, to guide the design of functionalized SERS
      nanoparticles for target detection. We further introduce the current status of
      label-free (direct) and labeled (indirect) SERS detections, for systems from
      biomolecules, to pathogens, to living cells, and we discuss the potential
      interferences from experimental design, measurement conditions, and data
      analysis. In the end, we give an outlook of the key challenges in bioanalytical
      SERS, including reproducibility, sensitivity, and spatial and time resolution.

PMID- 29638113
TI  - Advances in Tetrazine Bioorthogonal Chemistry Driven by the Synthesis of Novel
      Tetrazines and Dienophiles.
AB  - Bioorthogonal chemistry has found increased application in living systems over
      the past decade. In particular, tetrazine bioorthogonal chemistry has become a
      powerful tool for imaging, detection, and diagnostic purposes, as reflected in
      the increased number of examples reported in the literature. The popularity of
      tetrazine ligations are likely due to rapid and tunable kinetics, the existence
      of high quality fluorogenic probes, and the selectivity of reaction. In this
      Account, we summarize our recent efforts to advance tetrazine bioorthogonal
      chemistry through improvements in synthetic methodology, with an emphasis on
      developing new routes to tetrazines and expanding the range of useful
      dienophiles. These efforts have removed specific barriers that previously limited
      tetrazine ligations and have broadened their potential applications. Among other
      advances, this Account describes how our group discovered new methodology for
      tetrazine synthesis by developing a Lewis acid-promoted, one-pot method for
      generating diverse symmetric and asymmetric alkyl tetrazines with functional
      substituents in satisfactory yields. We attached these tetrazines to
      microelectrodes and succeeded in controlling tetrazine ligation by changing the
      redox state of the reactants. Using this electrochemical control process, we were
      able to modify an electrode surface with redox probes and enzymes in a site
      selective fashion. This Account also describes how our group improved the ability
      of tetrazines to act as fluorogenic probes by developing a novel elimination-Heck
      cascade reaction to synthesize alkenyl tetrazine derivatives. In this approach,
      tetrazine was conjugated to fluorophores to produce strongly quenched probes
      that, after bioorthogonal reaction, are "turned on" to enhance fluorescence, in
      many cases by >100-fold. These probes have allowed no-wash fluorescence imaging
      in living cells and intact animals. Finally, this Account reviews our efforts to
      expand the range of dienophile substrates to make tetrazine bioorthogonal
      chemistry compatible with specific biochemical and biomedical applications. We
      found that methylcyclopropene is sufficiently stable and reactive in the
      biological milieu to act as an efficient dienophile. The small size of the
      reactive tag minimizes steric hindrance, allowing cyclopropene to serve as a
      metabolic reporter group to reveal biological dynamics and function. We also used
      norbornadiene derivatives as strained dienophiles to undergo tetrazine-mediated
      transfer (TMT) reactions involving tetrazine ligation followed by a retro-Diels
      Alder process. This TMT reaction generates a pair of nonligating products. Using
      nucleic acid-templated chemistry, we have combined the TMT reaction with our
      fluorogenic tetrazine probes to detect endogenous oncogenic microRNA at picomolar
      concentrations. In a further display of dienophile versatility, we used a novel
      vinyl ether to cage a near-infrared fluorophore in a nonfluorescent form. Then we
      opened the cage in a "click to release" tetrazine bioorthogonal reaction,
      restoring the fluorescent form of the fluorophore. Combining this label with a
      corresponding nucleic acid probe allowed fluorogenic detection of target mRNA. In
      summary, this Account describes improvements in tetrazine and dienophile
      synthesis and application to advance tetrazine bioorthogonal chemistry. These
      advances have further enabled application of tetrazine ligation chemistry, not
      only in fundamental research but also in diagnostic studies.

PMID- 29638114
TI  - A Transcription Factor-Based Biosensor for Detection of Itaconic Acid.
AB  - Itaconic acid is an important platform chemical that can easily be incorporated
      into polymers and has the potential to replace petrochemical-based acrylic or
      methacrylic acid. A number of microorganisms have been developed for the
      biosynthesis of itaconate including Aspergillus terreus, Escherichia coli, and
      Saccharomyces cerevisiae. However, the number of strains and conditions that can
      be tested for increased itaconate titers are currently limited because of the
      lack of high-throughput screening methods. Here we identified itaconate-inducible
      promoters and their corresponding LysR-type transcriptional regulators from
      Yersinia pseudotuberculosis and Pseudomonas aeruginosa. We show that the YpItcR/P
      ccl inducible system is highly inducible by itaconic acid in the model
      gammaproteobacterium E. coli and the betaproteobacterium Cupriavidus necator (215
      and 105-fold, respectively). The kinetics and dynamics of the YpItcR/P ccl
      inducible system are investigated, and we demonstrate, that in addition to
      itaconate, the genetically encoded biosensor is capable of detecting mesaconate,
      cis-, and trans-aconitate in a dose-dependent manner. Moreover, the fluorescence
      based biosensor is applied in E. coli to identify the optimum expression level of
      cadA, the product of which catalyzes the conversion of cis-aconitate into
      itaconate. The fluorescence output is shown to correlate well with itaconate
      concentrations quantified using high-performance liquid chromatography coupled
      with ultraviolet spectroscopy. This work highlights the potential of the YpItcR/P
      ccl inducible system to be applied as a biosensor for high-throughput microbial
      strain development to facilitate improved itaconate biosynthesis.

PMID- 29638115
TI  - Correction to Forward Osmosis Membranes under Null-pressure Condition: Do
      Hydraulic and Osmotic Pressures Have Identical Nature?

PMID- 29638116
TI  - Influence of the Diphosphine Coordination Mode on the Structural and Optical
      Properties of Cyclometalated Platinum(II) Complexes: An Experimental and
      Theoretical Study on Intramolecular Pt...Pt and pi...pi Interactions.
AB  - The reaction of [Pt(C^N)(CF3CO2)(SMe2)] (1), in which C^N is either benzo[
      h]quinolinate (bhq), 1a, or 2-phenylpyridinate (ppy), 1b, with 1 equiv of
      bis(diphenylphosphino)methane (dppm) gave the bischelate complexes
      [Pt(C^N)dppm]CF3CO2 (2). The binuclear complexes [Pt2(C^N)2(CF3CO2)2(MU-dppm)]
      (3) were prepared, using an unusual reaction pathway, by the addition of
      equimolar amount of complexes 1 and 2, through the ring opening of the chelating
      dppm ligand and coordination of the CF3CO2 anion to the platinum center. The
      proposed reaction pathway and effect of the solvent polarity were investigated by
      density functional theory (DFT) calculations. The crystal structure of 3a shows
      considerable intramolecular Pt...Pt and pi...pi interactions. The crystal
      structure and formation pathway toward 3 were compared with the similar analogue
      [Pt2(bhq)2(Cl)2(MU-dppm)] (5). All complexes were fully characterized using
      multinuclear NMR spectroscopy and elemental analysis. Furthermore, the crystal
      structures of some complexes including 1b, 2a, 2b, 3a, and 5 were confirmed by X
      ray crystallography. The effect of dimerization via a change in the coordination
      mode of dppm, from a chelate mode in complex 2 to a bridge mode in complexes 3
      and 5, upon the excited states of the studied compounds was investigated in their
      distinguished absorption and emission profiles. The appearance of a remarkably
      low energy band in the absorption spectra of 3, which was assigned to a metal
      metal to ligand charge transfer [MMLCT; dsigma*(Pt2) -> pi*(C^N)] transition
      showing negative solvatochromism, is important evidence for the Pt...Pt
      intramolecular interaction. The vibronically resolved and long-lifetime emission
      of 2a in poly(methyl methacrylate) media and powder states at 77 and 300 K, along
      with time-dependent DFT calculations, suggested that the triplet ligand-centered
      (3LC) emission was mixed with some 3MLCT character. Unstructured and short
      lifetime emission in 3 refers to the phosphorescence 3MMLCT [dsigma*(Pt2) ->
      pi*(C^N)] transition. Although complex 5 is a binuclear compound, the long
      distance of the Pt...Pt interaction caused the occurrence of the 3MMLCT
      transition to fade and act as a mononuclear unit, and the emission originated
      mostly from the 3MLCT transition. As a result, more metal participation leads to
      more red-shifted absorption and emission spectra of the studied complexes upon
      going from LC to MLCT to MMLCT transitions (lambdaabs and lambdaem: 3a > 3b > 5 >
      2a > 2b).

PMID- 29638117
TI  - Metal-Organic-Framework-Mediated Nitrogen-Doped Carbon for CO2 Electrochemical
      Reduction.
AB  - A nitrogen-doped carbon was synthesized through the pyrolysis of the well-known
      metal-organic framework ZIF-8, followed by a subsequent acid treatment, and has
      been applied as a catalyst in the electrochemical reduction of carbon dioxide.
      The resulting electrode shows Faradaic efficiencies to carbon monoxide as high as
      ~78%, with hydrogen being the only byproduct. The pyrolysis temperature
      determines the amount and the accessibility of N species in the carbon electrode,
      in which pyridinic-N and quaternary-N species play key roles in the selective
      formation of carbon monoxide.

PMID- 29638118
TI  - Activity of Antimicrobial Peptide Aggregates Decreases with Increased Cell
      Membrane Embedding Free Energy Cost.
AB  - Antimicrobial peptides (AMPs) are a promising alternative to antibiotics for
      mitigating bacterial infections, in light of increasing bacterial resistance to
      antibiotics. However, predicting, understanding, and controlling the
      antibacterial activity of AMPs remain a significant challenge. While peptide
      intramolecular interactions are known to modulate AMP antimicrobial activity,
      peptide intermolecular interactions remain elusive in their impact on peptide
      bioactivity. Herein, we test the relationship between AMP intermolecular
      interactions and antibacterial efficacy by controlling AMP intermolecular
      hydrophobic and hydrogen bonding interactions. Molecular dynamics simulations and
      Gibbs free energy calculations in concert with experimental assays show that
      increasing intermolecular interactions via interpeptide aggregation increases the
      energy cost for the peptide to embed into the bacterial cell membrane, which in
      turn decreases the AMP antibacterial activity. Our findings provide a route for
      predicting and controlling the antibacterial activity of AMPs against Gram
      negative bacteria via reductions of intermolecular AMP interactions.

PMID- 29638119
TI  - Profile and Content of Betalains in Plasma and Urine of Volunteers after Long
      Term Exposure to Fermented Red Beet Juice.
AB  - The aim of this study was to determine profile and content of betalains in
      volunteers' plasma and urine after long-term exposure to fermented red beet
      juice. During 6 weeks, 24 healthy volunteers consumed juice with a dose of 0.7 mg
      betalains/kg body weight. Betalains were analyzed by means of micro-HPLC-MS/MS.
      Twelve betalain derivatives were found in blood plasma and urine after juice
      intake. The highest betalains level in blood plasma (87.65 +/- 15.71 nmol/L) and
      urine (1.14 +/- 0.12 MUmol) was found after the first and second week of juice
      intake, respectively. During juice consumption, the contribution of betalain
      metabolites was higher than that of native betalains, and interindividual
      variability in profile and content of betalains was observed. Summarizing, it was
      observed that long-term and regular consumption of the juice causes stabilization
      of profile and content of betalains in physiological fluids of volunteers, which
      include native compounds and their decarboxylated and dehydrogenated metabolites.

PMID- 29638120
TI  - Quantitative Identification of Basic Growth Channels for Formation of
      Monodisperse Nanocrystals.
AB  - Different mechanisms are proposed to account formation of monodisperse
      nanocrystals in literature, each of which is usually proposed to explain one set
      of experimental observations. Here, a general model based on mass conservation is
      developed to fully describe all possible channels including free growth by direct
      incorporation of the monomers converted from the precursors, growth by
      dissolution of a portion of the regular nanocrystals in solution, and growth by
      dissolution of the clusters in solution. The new model provides convenient yet
      quantitative methods to determine the channel ratios at a given time.
      Experimentally, an automated microreactor system is developed and applied for
      synthesis of monodisperse CdS nanocrystals, which is coupled with liquid-phase
      Fourier transform infrared and UV-vis measurements to, respectively, determine
      precursor conversion and size/concentration of nanocrystals with high
      reproducibility (<1%) and proper time resolution (<1 s). Different from the most
      accepted model for formation of monodisperse nanocrystals, a burst of nucleation
      followed by growth of all nuclei by direct incorporation of the monomers
      converted from the precursors (or "focusing of size distribution"), all three
      basic channels are found to coexist during growth of monodisperse CdS
      nanocrystals. While the new theory and experimental methods are applied to study
      growth of monodisperse nanocrystals, they can be extended to offer a full kinetic
      picture for formation of colloidal nanocrystals.

PMID- 29638121
TI  - An Efficient Buchwald-Hartwig/Reductive Cyclization for the Scaffold
      Diversification of Halogenated Phenazines: Potent Antibacterial Targeting,
      Biofilm Eradication, and Prodrug Exploration.
AB  - Bacterial biofilms are surface-attached communities comprised of nonreplicating
      persister cells housed within a protective extracellular matrix. Biofilms display
      tolerance toward conventional antibiotics, occur in ~80% of infections, and lead
      to >500000 deaths annually. We recently identified halogenated phenazine (HP)
      analogues which demonstrate biofilm-eradicating activities against priority
      pathogens; however, the synthesis of phenazines presents limitations. Herein, we
      report a refined HP synthesis which expedited the identification of improved
      biofilm-eradicating agents. 1-Methoxyphenazine scaffolds were generated through a
      Buchwald-Hartwig cross-coupling (70% average yield) and subsequent reductive
      cyclization (68% average yield), expediting the discovery of potent biofilm
      eradicating HPs (e.g., 61: MRSA BAA-1707 MBEC = 4.69 MUM). We also developed
      bacterial-selective prodrugs (reductively activated quinone
      alkyloxycarbonyloxymethyl moiety) to afford HP 87, which demonstrated excellent
      antibacterial and biofilm eradication activities against MRSA BAA-1707 (MIC =
      0.15 MUM, MBEC = 12.5 MUM). Furthermore, active HPs herein exhibit negligible
      cytotoxic or hemolytic effects, highlighting their potential to target biofilms.

PMID- 29638122
TI  - Correction to "Evidence for Electron-Hole Pair Excitation in the Associative
      Desorption of H2 and D2 from Au(111)".

PMID- 29638123
TI  - Tn Antigen Mimics by Ring-Opening of Chiral Cyclic Sulfamidates with Carbohydrate
      C1- S- and C1- O-Nucleophiles.
AB  - Starting from commercially available ( S)-isoserine and effectively accessible (
      S)-alpha-methylserine, enantiopure cyclic sulfamidates have been prepared as
      chiral building blocks for the synthesis of various S- and O-glycosylated amino
      acid derivatives, including unnatural variants of the Tn antigen, through highly
      chemo-, regio-, and stereoselective nucleophilic ring-opening reactions with
      carbohydrate C1- S- and C1- O-nucleophiles.

PMID- 29638125
TI  - Template-Directed Synthesis of a Conjugated Zinc Porphyrin Nanoball.
AB  - We report the template-directed synthesis of a pi-conjugated 14-porphyrin
      nanoball. This structure consists of two intersecting nanorings containing six
      and 10 porphyrin units. Fluorescence upconversion spectroscopy experiments
      demonstrate that electronic excitation delocalizes over the whole three
      dimensional pi system in less than 0.3 ps if the nanoball is bound to its
      templates or over 2 ps if the nanoball is empty.

PMID- 29638126
TI  - Materials Informatics.

PMID- 29638124
TI  - Casein Hydrolysate with Glycemic Control Properties: Evidence from Cells, Animal
      Models, and Humans.
AB  - Evidence exists to support the role of dairy derived proteins whey and casein in
      glycemic management. The objective of the present study was to use a cell
      screening method to identify a suitable casein hydrolysate and to examine its
      ability to impact glycemia related parameters in an animal model and in humans.
      Following screening for the ability to stimulate insulin secretion in pancreatic
      beta cells, a casein hydrolysate was selected and further studied in the ob/ob
      mouse model. An acute postprandial study was performed in 62 overweight and obese
      adults. Acute and long-term supplementation with the casein hydrolysate in in
      vivo studies in mice revealed a glucose lowering effect and a lipid reducing
      effect of the hydrolysate (43% reduction in overall liver fat). The postprandial
      human study revealed a significant increase in insulin secretion ( p = 0.04)
      concomitant with a reduction in glucose ( p = 0.03). The area under the curve for
      the change in glucose decreased from 181.84 +/- 14.6 to 153.87 +/- 13.02 ( p =
      0.009). Overall, the data supports further work on the hydrolysate to develop
      into a functional food product.

PMID- 29638127
TI  - Is Calcium-Sensing Receptor a New Molecular Target toward Improving
      Gastrointestinal Health?

PMID- 29638129
TI  - Rediscovering the Monodispersity of Sulfonatocalix[4]arene-Based Micelles.
AB  - When the micellar aggregation number ( Nagg) is small enough (<30), the Nagg
      matches the value of vertexes of a regular polyhedron: Platonic solids, and
      demonstrates perfect monodispersity. These micelles are named Platonic micelles
      and are particularly found in the system of calix[4]arene-based micelles due to
      the rigid structure of the backbone molecule. Although sulfonatocalix[4]arene
      based micelles are among the most studied host molecules in supramolecular
      chemistry, their micellar properties as Platonic micelles have thus far been
      overlooked. In this study, we prepared various sulfonatocalix[4]arene-based
      amphiphiles bearing alkyl chains with different lengths and investigated their
      aggregation behavior. When the amphiphiles formed spherical micelles, they
      demonstrated monodispersity in terms of Nagg, whose value changed from 4 to 17,
      and then to 24, upon increasing the carbon number in each alkyl chain from C5 to
      C6, and then to C7, respectively. Although the numbers 17 and 24 do not match the
      vertices of regular polyhedra, these values can be reasonably explained by the
      Thomson problem, which considers the Coulomb potential for calculating the best
      packing on a sphere with multiple identical spherical caps. This study describes
      rediscovery of the monodispersity of sulfonatocalix[4]arene-based micelles, which
      is consistent with the idea of Platonic micelles.

PMID- 29638128
TI  - Convergent Synthesis of Sialyl LewisX- O-Core-1 Threonine.
AB  - Selectins are a class of cell adhesion molecules that play a critical role during
      the initial steps of inflammation. The N-terminal domain of P-selectin
      glycoprotein ligand-1 (PSGL-1) binds to all selectins, but with the highest
      affinity to P-selectin. Recent evidence suggests that the blockade of P
      selectin/PSGL-1 interactions provides a viable therapeutic option for the
      treatment of many inflammatory diseases. Herein, we report the total synthesis of
      threonine bearing sialyl LewisX (sLeX) linked to a Core-1- O-hexasaccharide 1, as
      a key glycan of the N-terminal domain of PSGL-1. A convergent synthesis using
      alpha-selective sialylation and a regioselective [4+2] glycosylation are the key
      features of this synthesis.

PMID- 29638131
TI  - Hindered Formation of Photoinactive delta-FAPbI3 Phase and Hysteresis-Free Mixed
      Cation Planar Heterojunction Perovskite Solar Cells with Enhanced Efficiency via
      Potassium Incorporation.
AB  - Organic-inorganic hybrid lead halide perovskite solar cells have demonstrated
      competitive power conversion efficiency over 22%; nevertheless, critical issues
      such as unsatisfactory device stability, serious current-voltage hysteresis, and
      formation of photo nonactive perovskite phases are obstacles for
      commercialization of this photovoltaics technology. Herein we report a facial yet
      effective method to hinder formation of photoinactive delta-FAPbI3 and hysteresis
      behavior in planar heterojunction perovskite solar cells based on K
      x(MA0.17FA0.83)1- xPbI2.5Br0.5 (0<= x <= 0.1) through incorporation of potassium
      ions (K+). X-ray diffraction patterns demonstrate formation of photoinactive
      delta-FAPbI3 was almost completely suppressed after K+ incorporation. Density
      functional theory calculation shows K+ prefers to enter the interstitial sites of
      perovskite lattice, leading to chemical environmental change in the crystal
      structure. Ultrafast transient absorption spectroscopy has revealed that K+
      incorporation leads to enhanced carrier lifetime by 50%, which is also confirmed
      by reduced trap-assisted recombination of the perovskite solar cells containing
      K+ in photovoltage decay. Ultraviolet photoelectron spectroscopy illustrates that
      K+ incorporation results in a significant rise of conduction band minimum of the
      perovskite material by 130 meV, leading to a more favorable energy alignment with
      electron transporting material. At the optimal content of 3% K+ (molar ratio,
      relative to the total monovalent cations), nearly hysteresis-free, enhanced power
      conversion efficiencies from 15.72% to 17.23% were obtained in this solar cell.

PMID- 29638133
TI  - Direct Hybridization of Hydrophobic Nanocrystals with Colloidal Silica via van
      der Waals Force.
AB  - We present a novel, direct approach to hybridize hydrophobic quantum dot (QD)
      nanocrystals with colloidal silica (A) via van der Waals (vdW) force only. The A
      is constructed by aggregation of 15-25 nm sized hydrophobic silica nanoparticles
      with octadecyl groups. For hybridization, the hydrophobic QDs sit on the crevices
      of A via reinforced vdW force by interdigitation of long-chained hydrocarbons
      along the enlarged contact area of the crevices. The hybrids (B) are easily
      encapsulated with silica with/without functional groups, yielding QD-layer
      incorporated silica particles (C) with greatly enhanced PL (up to 690%) and
      astonishing photostability compared with their free QDs under an identical QD
      concentration. This approach is simple, novel, versatile, and extended to the
      cases of three different sized QDs. The hydrophobic product C with phenylethyl
      groups is applicable to fabricate a white LED, and its hydrophilic analogues can
      be a promising material for bioapplications.

PMID- 29638130
TI  - Harnessing the beta-Silicon Effect for Regioselective and Stereoselective
      Rhodium(II)-Catalyzed C-H Functionalization by Donor/Acceptor Carbenes Derived
      from 1-Sulfonyl-1,2,3-triazoles.
AB  - The regioselective and enantioselective intermolecular sp3 C-H functionalization
      of silicon-substituted alkanes was accomplished using Rh2( S-NTTL)4 with readily
      available 1-sulfonyl-1,2,3-triazoles as carbene precursors. These reactions
      generate a diverse array of stereodefined substituted silaalkanes.

PMID- 29638132
TI  - Transmembrane Polyproline Helix.
AB  - The third most abundant polypeptide conformation in nature, the polyproline-II
      helix, is a polar, extended secondary structure with a local organization
      stabilized by intercarbonyl interactions within the peptide chain. Here we design
      a hydrophobic polyproline-II helical peptide based on an oligomeric
      octahydroindole-2-carboxylic acid scaffold and demonstrate its transmembrane
      alignment in model lipid bilayers by means of solid-state 19F NMR. As result, we
      provide a first example of a purely artificial transmembrane peptide with a
      structural organization that is not based on hydrogen-bonding.

PMID- 29638134
TI  - The Lithiation/Oxygenation Approach to Calix[6]arenes Selectively Functionalized
      at a Pair of Opposite Methylene Bridges.
AB  - Lithiation of the calix[6]arene methyl ether 2 followed by reaction with O2
      yields derivatives with two opposite methylene groups hydroxylated.
      Calix[6]arenes with two opposite bridges functionalized with alkoxy, azido, and m
      xylyl groups were prepared via reaction of a dichlorocalix[6]arene derivative
      with nucleophiles.

PMID- 29638135
TI  - In Vivo Introduction of mRNA Encapsulated in Lipid Nanoparticles to Brain
      Neuronal Cells and Astrocytes via Intracerebroventricular Administration.
AB  - Gene therapy is a promising strategy for curing certain types of brain diseases.
      Supplementation of therapeutic proteins such as aromatic amino acid decarboxylase
      (AADC) or nerve growth factor (NGF) have been reported to be successful examples
      of such treatments. However, there are safety concerns because these systems are
      based on virus-based gene vectors. A safe and efficient artificial carrier is
      thus urgently needed as an alternative. In this study, an mRNA based artificial
      gene carrier was introduced into the mouse brain via intracerebroventricular
      administration. As a carrier, a lipid nanoparticle (LNP) composed of
      environmentally sensitive lipid-like materials called an SS-cleavable proton
      activated lipid-like material is used. The apolipoprotein E mediated cellular
      uptake of the lipid nanoparticles is one of the key features for its superior and
      homogeneous transfection activity compared to commercially available transfection
      reagents in both in vitro and in vivo situations. Immunostaining of brain
      specimens suggested that exogenous proteins can be introduced into neuronal cells
      as well as astrocytes using the mRNA-based gene carrier. This cannot be achieved
      using DNA-based artificial gene carriers. The findings suggest that a combination
      of an mRNA and a lipid based delivery system have great promise as a platform for
      the treatment of brain disorders.

PMID- 29638136
TI  - Sarinfacetamides A and B, Nitrogenous Diterpenoids with
      Tricyclo[6.3.1.01,5]dodecane Scaffold from the South China Sea Soft Coral
      Sarcophyton infundibuliforme.
AB  - Two novel nitrogenous diterpenoids, sarinfacetamides A (1) and B (2), featuring
      an uncommon tricyclo[6.3.1.01,5]dodecane scaffold, and a known related diterpene
      (3) were isolated from the South China Sea soft coral Sarcophyton
      infundibuliforme. Their structures, including the absolute configuration of 1,
      were established by extensive spectroscopic analysis and TDDFT-ECD calculation.
      Compounds 1 and 3 exhibited interesting promotion effects on the ConA-induced T
      lymphocyte proliferation. A plausible biosynthetic pathway for 1 and 2 was also
      proposed.

PMID- 29638137
TI  - Electrocapillary Coupling at Metal Surfaces from First Principles: On the Impact
      of Excess Charge on Surface Stress and Relaxation.
AB  - We study the response of the surface stress to excess charge via ab initio
      simulation of metal surfaces in an external electric field. We focus on "simple"
      sp-bonded metals to gain insight into the mechanisms underlying electrocapillary
      coupling. Both the direct effect on the surface stress via charging of the bonds
      and the indirect effect resulting from the charge-induced relaxation are analyzed
      and discussed in relation to the trends of the coupling coefficients, which-owing
      to a Maxwell relation-are determined in terms of the response of the work
      function to strain. Al(111), Mg(0001), and Na(110) are investigated as
      prototypical sp-bonded metal surfaces with positive, vanishing, and negative
      coupling parameters, respectively. Mg(0001) and Al(111) exhibit an inward
      relaxation of the first atomic layer upon negative charging, whereas an outward
      relaxation occurs for Na(110). The indirect contribution of the relaxation to the
      coupling coefficient has the same sign as the total response and makes up about
      30% of its magnitude for Al(111) and Na(110). Our study highlights that even the
      response behavior of the so-called simple metals is by no means readily captured
      within simple models.

PMID- 29638139
TI  - Corrigendum to 10.1177/2048872615574706.

PMID- 29638138
TI  - CORRECTION.

PMID- 29638141
TI  - Steroid-Induced Psychosis in the Pediatric Population: A New Case and Review of
      the Literature.
AB  - OBJECTIVES: Iatrogenic steroid-induced psychosis is a rare but serious adverse
      side effect seen largely in the adult population that less commonly affects
      children and adolescents. Given the significant distress steroid-induced
      psychosis may cause, recommendations are needed for effective management. Here we
      conducted a systematic review of the literature and report a new case of steroid
      induced psychosis in a 12-year-old patient. METHODS: We performed a systematic
      search using Embase, PubMed, Scopus, and PsychInfo. Key terms included ("steroid
      induced" or "corticosteroid induced" or "glucocorticoid induced") and
      ("psychosis" or "hallucinations" or "delusions") and ("child" or "adolescent" or
      "pediatric"). A total of 15 articles of steroid-induced psychosis in children and
      adolescents were found in the scientific literature. This report includes those
      articles and a novel case of steroid-induced psychosis. RESULTS: Children with
      asthma, autoimmune diseases, and cancer have been reported to experience steroid
      induced psychosis. The mean age of children with steroid-induced psychosis was 12
      +/- 3.6 years. Our team presents a report of steroid-induced psychosis in a 12
      year-old patient with discoid-type lupus erythematosus. Within days of treatment
      with 40 mg prednisone daily, this patient began to drool, became mute, and was
      responding to internal stimuli. Treatment was difficult secondary to the acute
      exacerbation of lupus, requiring ongoing therapy. It was initially unclear
      whether the acute psychosis was a manifestation of lupus, a side effect of
      medication, or a combination of the two risk factors. Neurology consultation
      ruled out lupus cerebritis. Psychosis was treated with haloperidol 5 mg.
      Psychosis did not resolve until the steroid taper was complete and the patient
      was no longer taking any prednisone. CONCLUSIONS: Given the common use of
      glucocorticoid therapy in children, it is important that physicians and parents
      recognize the signs of steroid-induced psychosis and are aware of the data on
      treating this complication.

PMID- 29638140
TI  - Mycobacterial infection influences bone biomarker levels in patients with Crohn's
      disease.
AB  - Patients with Crohn's disease (CD) have higher risk for osteoporosis following
      decreased level of osteocalcin. We hypothesize that active inflammation following
      Mycobacterium avium subsp. paratuberculosis (MAP) infection results in elevation
      of undercarboxylated osteocalcin (ucOC) and downregulation of active osteocalcin
      in CD patients and cow-disease model (Johne's disease). In this study, we
      measured ucOC, active osteocalcin, and calcium levels in sera from 42 cattle (21
      infected with MAP and 21 healthy cattle), 18 CD patients, and 20 controls. The
      level of ucOC in MAP+ bovine samples was higher than that in MAP- controls (318
      +/- 57.2 nmol/mL vs. 289 +/- 95.8 nmol/mL, P > 0.05). Consequently, mean calcium
      level in bovine MAP+ was significantly higher than that in bovine-MAP- samples
      (9.98 +/- 0.998 mg/dL vs. 7.65 +/- 2.12 mg/dL, P < 0.05). Also, the level of ucOC
      was higher in CD-MAP+ than in CD-MAP- (561 +/- 23.7 nmol/mL vs. 285 +/- 19.6
      nmol/mL, P < 0.05). Interestingly, the mean osteocalcin level in MAP+ bovine was
      lower than that in MAP- bovine (797 +/- 162 pg/mL vs. 1190 +/- 43 pg/mL) and it
      was lower in CD-MAP+ than in CD-MAP- infection (1.89 +/- 0.184 ng/mL vs. 2.19 +/-
      0.763 ng/mL) (P < 0.05). The correlation between MAP infection and elevation of
      sera ucOC, reduction of active osteocalcin and increased calcium supports MAP
      infection role in CD and complications with osteoporosis.

PMID- 29638142
TI  - Patient-reported outcomes are independent predictors of one-year mortality and
      cardiac events across cardiac diagnoses: Findings from the national DenHeart
      survey.
AB  - Aims Patient-reported quality of life and anxiety/depression scores provide
      important prognostic information independently of traditional clinical data. The
      aims of this study were to describe: (a) mortality and cardiac events one year
      after hospital discharge across cardiac diagnoses; (b) patient-reported outcomes
      at hospital discharge as a predictor of mortality and cardiac events. Design A
      cross-sectional survey with register follow-up. Methods Participants: All
      patients discharged from April 2013 to April 2014 from five national heart
      centres in Denmark. Main outcomes Patient-reported outcomes: anxiety and
      depression (Hospital Anxiety and Depression Scale); perceived health (Short Form
      12); quality of life (HeartQoL and EQ-5D); symptom burden (Edmonton Symptom
      Assessment Scale). Register data: mortality and cardiac events within one year
      following discharge. Results There were 471 deaths among the 16,689 respondents
      in the first year after discharge. Across diagnostic groups, patients reporting
      symptoms of anxiety had a two-fold greater mortality risk when adjusted for age,
      sex, marital status, educational level, comorbidity, smoking, body mass index and
      alcohol intake (hazard ratio (HR) 1.92, 95% confidence interval (CI) 1.52-2.42).
      Similar increased mortality risks were found for patients reporting symptoms of
      depression (HR 2.29, 95% CI 1.81-2.90), poor quality of life (HR 0.46, 95% CI
      0.39-0.54) and severe symptom distress (HR 2.47, 95% CI 1.92-3.19). Cardiac
      events were predicted by poor quality of life (HR 0.71, 95% CI 0.65-0.77) and
      severe symptom distress (HR 1.58, 95% CI 1.35-1.85). Conclusions Patient-reported
      mental and physical health outcomes are independent predictors of one-year
      mortality and cardiac events across cardiac diagnoses.

PMID- 29638143
TI  - Lung Ultrasound and Microbubbles Enhance Aminoglycoside Efficacy and Delivery to
      the Lung in Escherichia coli-induced Pneumonia and Acute Respiratory Distress
      Syndrome.

PMID- 29638144
TI  - Breastfeeding and the United States Opioid Epidemic.

PMID- 29638145
TI  - Prevalence and reporting of recruitment, randomisation and treatment errors in
      clinical trials: A systematic review.
AB  - Background/aims In clinical trials, it is not unusual for errors to occur during
      the process of recruiting, randomising and providing treatment to participants.
      For example, an ineligible participant may inadvertently be randomised, a
      participant may be randomised in the incorrect stratum, a participant may be
      randomised multiple times when only a single randomisation is permitted or the
      incorrect treatment may inadvertently be issued to a participant at
      randomisation. Such errors have the potential to introduce bias into treatment
      effect estimates and affect the validity of the trial, yet there is little
      motivation for researchers to report these errors and it is unclear how often
      they occur. The aim of this study is to assess the prevalence of recruitment,
      randomisation and treatment errors and review current approaches for reporting
      these errors in trials published in leading medical journals. Methods We
      conducted a systematic review of individually randomised, phase III, randomised
      controlled trials published in New England Journal of Medicine, Lancet, Journal
      of the American Medical Association, Annals of Internal Medicine and British
      Medical Journal from January to March 2015. The number and type of recruitment,
      randomisation and treatment errors that were reported and how they were handled
      were recorded. The corresponding authors were contacted for a random sample of
      trials included in the review and asked to provide details on unreported errors
      that occurred during their trial. Results We identified 241 potentially eligible
      articles, of which 82 met the inclusion criteria and were included in the review.
      These trials involved a median of 24 centres and 650 participants, and 87%
      involved two treatment arms. Recruitment, randomisation or treatment errors were
      reported in 32 in 82 trials (39%) that had a median of eight errors. The most
      commonly reported error was ineligible participants inadvertently being
      randomised. No mention of recruitment, randomisation or treatment errors was
      found in the remaining 50 of 82 trials (61%). Based on responses from 9 of the 15
      corresponding authors who were contacted regarding recruitment, randomisation and
      treatment errors, between 1% and 100% of the errors that occurred in their trials
      were reported in the trial publications. Conclusion Recruitment, randomisation
      and treatment errors are common in individually randomised, phase III trials
      published in leading medical journals, but reporting practices are inadequate and
      reporting standards are needed. We recommend researchers report all such errors
      that occurred during the trial and describe how they were handled in trial
      publications to improve transparency in reporting of clinical trials.

PMID- 29638146
TI  - Detecting Nonvolatile Life- and Nonlife-Derived Organics in a Carbonaceous
      Chondrite Analogue with a New Multiplex Immunoassay and Its Relevance for
      Planetary Exploration.
AB  - Potential martian molecular targets include those supplied by meteoritic
      carbonaceous chondrites such as amino acids and polycyclic aromatic hydrocarbons
      and true biomarkers stemming from any hypothetical martian biota (organic
      architectures that can be directly related to once living organisms). Heat
      extraction and pyrolysis-based methods currently used in planetary exploration
      are highly aggressive and very often modify the target molecules making their
      identification a cumbersome task. We have developed and validated a mild,
      nondestructive, multiplex inhibitory microarray immunoassay and demonstrated its
      implementation in the SOLID (Signs of Life Detector) instrument for simultaneous
      detection of several nonvolatile life- and nonlife-derived organic molecules
      relevant in planetary exploration and environmental monitoring. By utilizing a
      set of highly specific antibodies that recognize D- or L- aromatic amino acids
      (Phe, Tyr, Trp), benzo[a]pyrene (B[a]P), pentachlorophenol, and sulfone
      containing aromatic compounds, respectively, the assay was validated in the SOLID
      instrument for the analysis of carbon-rich samples used as analogues of the
      organic material in carbonaceous chondrites or even Mars samples. Most of the
      antibodies enabled sensitivities at the 1-10 ppb level and some even at the ppt
      level. The multiplex immunoassay allowed the detection of B[a]P as well as
      aromatic sulfones in a water/methanol extract of an Early Cretaceous lignite
      sample (c.a., 140 Ma) representing type IV kerogen. No L- or D-aromatic amino
      acids were detected, reflecting the advanced diagenetic stage and the fossil
      nature of the sample. The results demonstrate the ability of the liquid
      extraction by ultrasonication and the versatility of the multiplex inhibitory
      immunoassays in the SOLID instrument to discriminate between organic matter
      derived from life and nonlife processes, an essential step toward life detection
      outside Earth.

PMID- 29638147
TI  - The absolute bioavailability and the effect of food on a new magnesium lactate
      dihydrate extended-release caplet in healthy subjects.
AB  - OBJECTIVE: To assess the absolute bioavailability of 20 mEq magnesium lactate
      extended-release (ER) caplets and to assess the effect of food on the
      pharmacokinetics of these ER caplets. SIGNIFICANCE: Magnesium in different salt
      forms is available as over-the-counter oral formulations. The absorption and
      bioavailability is highly affected by the water solubility of the salt form. A
      new ER caplet of 10 mEq strength of magnesium L-lactate dihydrate has been
      developed to increase the bioavailability of magnesium. METHODS: An open label,
      single-dose, randomized, three-period, cross-over study in healthy adults was
      conducted with three treatments: (a) single oral dose of 20 mEq magnesium L
      lactate dehydrate under fasting conditions, (b) single intravenous (IV) infusion
      of 20 mEq magnesium sulfate, and (c) single oral dose of 20 mEq magnesium L
      lactate dehydrate under fed conditions. Urine and blood samples were collected
      for analysis of urinary and serum magnesium concentrations. RESULTS: Absolute
      bioavailabilities of the caplets under fasted and fed conditions, compared to IV
      magnesium sulfate, were 20.26% (fasted) and 12.49% (fed) in serum, based on the
      geometric mean ratio (GMR) of the baseline-adjusted AUC0-72, and 38.11% (fasted)
      and 40.99% (fed) in urine, based on the GMR of the baseline-adjusted Ae0-72.
      Relative bioavailability of the caplets comparing the fed and fasted states was
      61.67% in serum, based on the GMR of the baseline-adjusted AUC0-72, and 107.57%
      in urine, based on the GMR of the baseline-adjusted Ae0-72. CONCLUSIONS: This new
      magnesium formulation has reasonable bioavailability and might be a valuable
      addition to the currently available magnesium oral products.

PMID- 29638149
TI  - Masitinib in treatment of pancreatic cancer.
AB  - INTRODUCTION: Pancreatic cancer continues to have high mortality despite the
      development of many chemotherapeutic agents. The 5-year relative survival for
      stage IV patients is less than 3%. This urgent unmet need warrants the
      development of novel and active therapeutic agents, which focus both on targeting
      cancer cells and modifying the microenvironment of cancer cells. Areas covered:
      In this article, the authors review the development of masitinib, a novel
      tyrosine kinase inhibitor of numerous targets, including c-Kit, PDGFR and FGFR.
      This review covers its development from the bench to clinical trials assessing
      its potential in pancreatic cancer. Expert opinion: While masitinib has not shown
      an increase in overall survival (OS) or progression free survival (PFS) compared
      to the current standard of care in patients with pancreatic adenocarcinoma,
      masitinib may have a role in decreasing inflammation related to those patients
      with increased pain scores with pancreatic adenocarcinoma. If we have the tools
      to identify accurate subgroups of patients who may benefit from particular
      therapies, this agent may be of benefit to these patients. Indeed, if more
      sophisticated biomarkers and the identification of patient subgroups are better
      explained, the authors believe that masitinib will become part of the
      armamentarium against pancreatic adenocarcinoma.

PMID- 29638148
TI  - Prevention of upper gastrointestinal bleeding in critically ill Chinese patients:
      a randomized, double-blind study evaluating esomeprazole and cimetidine.
AB  - OBJECTIVE: To assess the efficacy and safety of esomeprazole in preventing upper
      gastrointestinal (GI) bleeding in critically ill Chinese patients, using
      cimetidine as an active comparator. METHODS: A pre-specified non-inferiority
      limit (5%) was used to compare rates of significant upper GI bleeding in this
      randomized, double-blind, parallel-group, phase 3 study across 27 intensive care
      units in China. Secondary endpoints included safety and tolerability measures.
      Patients required mechanical ventilation and had at least one additional risk
      factor for stress ulcer bleeding. Patients were randomized to receive either
      active esomeprazole 40 mg, as a 30-min intravenous (IV) infusion twice daily, and
      an IV placebo cimetidine infusion or active cimetidine 50 mg/h, as a continuous
      infusion following an initial bolus of 300 mg, and placebo esomeprazole
      injections, given up to 14 days. Patients were blinded using this double-dummy
      technique. RESULTS: Of 274 patients, 2.7% with esomeprazole and 4.6% with
      cimetidine had significant upper GI bleeding (bright red blood in the gastric
      tube not clearing after lavage or persistent Gastroccult-positive "coffee
      grounds" material). Non-inferiority of esomeprazole to cimetidine was
      demonstrated. The safety profiles of both drugs were similar and as expected in
      critically ill patients. CONCLUSIONS: Esomeprazole is effective in preventing
      upper GI bleeding in critically ill Chinese patients, as demonstrated by the non
      inferiority analysis using cimetidine as an active control. TRIAL REGISTRATION:
      ClinicalTrials.gov identifier NCT02157376.

PMID- 29638152
TI  - How Will Virtual Reality Impact Our Understanding of Sexuality?

PMID- 29638150
TI  - Emerging drugs for primary progressive multiple sclerosis.
AB  - INTRODUCTION: The identification of effective therapies for progressive forms of
      multiple sclerosis (MS) has remains a priority and challenge for the global MS
      community. Despite a few proposed mechanisms, a more complete understanding of
      the mechanisms involved in the pathogenesis of these MS phenotypes, animal models
      that incorporate these pathogenic characteristics, novel trial designs, drug
      repurposing strategies, and new models of collaboration between clinical and
      basic science personnel may be required in identifying effective therapies. Areas
      covered: Here, we review the current knowledge on putative pathogenic mechanisms
      in primary progressive MS (PPMS). Also, the rationale and outcomes of key phase
      II or III trial initiatives in PPMS are summarized. Future perspectives are
      outlined. Expert opinion: The recent approval of ocrelizumab is a major milestone
      forward in the therapy of PPMS. One reason for success of this drug is
      appropriate patient selection. The ultimate goal in PPMS therapy should be the
      reversal of disability, and the arrest of disease progression. Our current
      understanding of PPMS suggests that a combination of immune-modulatory, myelin
      restorative, and neuro-regenerative therapies particularly early in the disease
      course would be a reasonable strategy. Finally, selection of appropriate
      patients, selection of appropriate outcomes and monitoring therapy is again
      crucial for success of therapeutic strategies.

PMID- 29638153
TI  - WeChat Addiction Suppresses the Impact of Stressful Life Events on Life
      Satisfaction.
AB  - The current study examined the influences of stressful life events and WeChat
      addiction on life satisfaction, and investigated the mediating role of WeChat
      addiction on the relationship between the two research variables. A total of 463
      undergraduates completed self-reported scales for stressful life events, WeChat
      addiction, and life satisfaction. Structural equation modeling was used to
      analyze the questionnaire data. The results showed the suppressing effect of
      WeChat addiction on the negative impact of stressful life events on life
      satisfaction. Stressful life events affect life satisfaction both directly and
      indirectly. Stressful life events are positively associated with WeChat
      addiction, which exerts positive impact on life satisfaction. The contributions
      of the findings are discussed.

PMID- 29638155
TI  - Interactive Effects of Instagram Foodies' Hashtagged #Foodporn and Peer Users'
      Eating Disorder on Eating Intention, Envy, Parasocial Interaction, and Online
      Friendship.
AB  - Drawing from social comparison theory, parasocial interaction (PSI) theory, and
      the literature on envy, a randomized experiment addressed the dynamics of body
      image, fame, and envy in the context of foodies' foodporn posting on Instagram.
      Using a 2 (foodie's body type: fat vs. thin) * 2 (foodie's Instagram popularity:
      unpopular vs. popular) between-subjects design, this experiment (N = 141)
      examined the effects of an Instagram foodie's body shape and popularity level on
      peer Instagram users' eating intention, envy, and PSI with the Instagram foodie.
      The results showed main effects of an Instagram foodie's body shape on peer
      users' eating intention, and moderating effects of users' self-esteem, body mass
      index, perfectionism, anorexia, and bulimia nervosa. Additionally, envy mediated
      the effects of the Instagram foodie's body shape and popularity on peer users'
      PSI with the foodie and intention to build an Instagram-based friendship.
      Theoretical contributions to the literature on social comparison and eating
      disorder and practical implications for fitspiration and social media-based
      health interventions are discussed.

PMID- 29638156
TI  - The Effects of Avatars' Age on Older Adults' Self-Disclosure and Trust.
AB  - Older adults are increasingly interacting with other people online via virtual
      avatars, yet little is known about how avatars affect older adults' behavior.
      This study examines how interacting avatars' age affects older adult's self
      disclosure and trust in a relation-building context. Previous studies have found
      that users can take on behaviors consistent with characteristics of the avatars.
      In social interactions, people also assess their avatar in relation to other
      avatars for similarity or differences. We conducted a 2 (self-avatar: old vs.
      young) * 2 (other's avatar: old vs. young) experiment with older-adult
      participants aged 60+ (n = 95). The findings show that using younger avatars did
      not increase self-disclosure. However, the older-adult participants disclosed
      more information when their avatar's age matched their partner avatar's age
      (i.e., old to old, young to young). They also trust their partners more when the
      interacting avatars shared similar age. This study provides theoretical insights
      into the role of avatars in online relationship-building and extends our
      understanding of the avatar effects on older adults.

PMID- 29638157
TI  - Is Media Multitasking Good for Cybersecurity? Exploring the Relationship Between
      Media Multitasking and Everyday Cognitive Failures on Self-Reported Risky
      Cybersecurity Behaviors.
AB  - The current study focused on how engaging in media multitasking (MMT) and the
      experience of everyday cognitive failures impact on the individual's engagement
      in risky cybersecurity behaviors (RCsB). In total, 144 participants (32 males,
      112 females) completed an online survey. The age range for participants was 18 to
      43 years (M = 20.63, SD = 4.04). Participants completed three scales which
      included an inventory of weekly MMT, a measure of everyday cognitive failures,
      and RCsB. There was a significant difference between heavy media multitaskers
      (HMM), average media multitaskers (AMM), and light media multitaskers (LMM) in
      terms of RCsB, with HMM demonstrating more frequent risky behaviors than LMM or
      AMM. The HMM group also reported more cognitive failures in everyday life than
      the LMM group. A regression analysis showed that everyday cognitive failures and
      MMT acted as significant predictors for RCsB. These results expand our current
      understanding of the relationship between human factors and cybersecurity
      behaviors, which are useful to inform the design of training and intervention
      packages to mitigate RCsB.

PMID- 29638158
TI  - Expression of ILK in renal stroma is essential for multiple aspects of renal
      development.
AB  - Kidney development involves reciprocal and inductive interactions between the
      ureteric bud (UB) and surrounding metanephric mesenchyme. Signals from renal
      stromal lineages are essential for differentiation and patterning of renal
      epithelial and mesenchymal cell types and renal vasculogenesis; however,
      underlying mechanisms remain not fully understood. Integrin-linked kinase (ILK),
      a key component of integrin signaling pathway, plays an important role in kidney
      development. However, the role of ILK in renal stroma remains unknown. Here, we
      ablated ILK in renal stromal lineages using a platelet-derived growth factor
      receptor B ( Pdgfrb) -Cre mouse line, and the resulting Ilk mutant mice presented
      postnatal growth retardation and died within 3 wk of age with severe renal
      developmental defects. Pdgfrb-Cre;Ilk mutant kidneys exhibited a significant
      decrease in UB branching and disrupted collecting duct formation. From E16.5
      onward, renal interstitium was disorganized, forming medullary interstitial
      pseudocysts. Pdgfrb-Cre;Ilk mutants exhibited renal vasculature mispatterning and
      impaired glomerular vascular differentiation. Impaired glial cell-derived
      neurotrophic factor/Ret and bone morphogenetic protein 7 signaling pathways were
      observed in Pdgfrb-Cre;Ilk mutant kidneys. Furthermore, phosphoproteomic and
      Western blot analyses revealed a significant dysregulation of a number of key
      signaling pathways required for kidney morphogenesis, including PI3K/AKT and
      MAPK/ERK in Pdgfrb-Cre;Ilk mutants. Our results revealed a critical requirement
      for ILK in renal-stromal and vascular development, as well as a noncell
      autonomous role of ILK in UB branching morphogenesis.

PMID- 29638159
TI  - Klotho plays a protective role against glomerular hypertrophy in a cell cycle
      dependent manner in diabetic nephropathy.
AB  - There are few studies on the effect of klotho on podocytes in diabetic
      nephropathy. Thus, we tested whether klotho exerts a protective effect against
      glomerular injury in diabetes. Mouse podocytes were cultured in media containing
      5.6 or 30 mM glucose(HG) with or without 200 pM of recombinant klotho (rKL).
      Additionally, 32 mice were injected intraperitoneally with either diluent( n =
      16, C) or with streptozotocin ( n = 16, DM). Control and diabetic mice underwent
      sham operation and unilateral nephrectomy, respectively. Eight mice from each
      control and DM group were treated daily with 10 MUg.kg-1.day-1 of rKL, using an
      osmotic minipump. Klotho was expressed in podocytes, and its expression was
      dependent on peroxisome proliferator-activateed receptor-gamma (PPARgamma). HG
      treatment increased the expression of cell cycle-related and apoptotic markers,
      and these were significantly attenuated by rKL; rKL inhibited the extracellular
      signal-regulated protein kinase-1/2 and p38 signaling pathways in HG-induced
      podocyte injury. However, siRNA against klotho gene in HG-treated podocytes
      failed to aggravate cell cycle arrest and apoptosis. When HG-treated podocytes
      were incubated in the high-klotho-conditioned medium from tubular epithelial
      cells, cell injury was significantly attenuated. This effect was not observed
      when klotho was inhibited by siRNA. In vivo, the expressions of cell cycle
      related and apoptotic markers were increased in diabetic mice compared with
      controls, which were significantly decreased by rKL. Glomerular hypertrophy (GH)
      and increased profibrotic markers were significantly alleviated after rKL
      administration. These results showed that klotho was expressed in glomerular
      podocytes that and its expression was regulated by PPARgamma. Additionally,
      administration of rKL attenuated GH via a cell cycle-dependent mechanism and
      decreased apoptosis.

PMID- 29638160
TI  - Distinct morphological features of acute tubular injury in renal allografts
      correlate with clinical outcome.
AB  - Acute tubular injury (ATI) is common in renal allografts and is related to
      inferior long-term allograft function. However, it is unknown which of the
      morphological features of ATI can predict outcome and how they should be graded.
      Here, we examine features of ATI systematically in protocol biopsies and biopsies
      for cause to define the most predictive features. Analyses included 521 protocol
      biopsies taken at 6 wk, 3 mo, and 6 mo after transplantation and 141 biopsies for
      cause from 204 patients. Features of ATI included brush border loss, tubular
      epithelial lucency, flattening, pyknosis, nuclei loss, and luminal debris, each
      graded semiquantitatively. Additional immunohistochemical stainings were
      performed for markers of cell injury (neutrophil gelatinase-associated
      lipocalin), cell death [cleaved caspase-3, fatty acid-coenzyme A ligase 4
      (FACL4)], and proliferation (Ki-67). Interobserver reliability was good for
      pyknosis, flattening, and brush border loss and poor for lucency, nuclei loss,
      and luminal debris. In protocol biopsies between 6 wk and 6 mo, the degree of ATI
      remained virtually unchanged. Biopsies for cause had generally higher injury
      scores. Deceased donor source, delayed graft function, ganciclovir/valganciclovir
      treatment, and urinary tract infection correlated with ATI. The degree of
      pyknosis, flattening, and brush border loss correlated best with impaired
      allograft function. FACL4 expression was observed in areas of ATI. Only patients
      with Ki-67 expression showed stable or improved allograft function in the
      longitudinal assessment. Reliable assessment of ATI is possible by
      semiquantitative grading of tubular epithelial cell brush border loss,
      flattening, and pyknosis. Examination of Ki-67 expression can help determine the
      potential for recovery from this damage.

PMID- 29638161
TI  - Plasma Insulin Levels and Hypoglycemia Affect Subcutaneous Interstitial Glucose
      Concentration.
AB  - BACKGROUND: Continuous glucose monitoring (CGM) accuracy during hypoglycemia is
      suboptimal. This might be partly explained by insulin or hypoglycemia-induced
      changes in the plasma interstitial subcutaneous (SC) fluid glucose gradient. The
      aim of the present study was to assess the role of plasma insulin (PI) and
      hypoglycemia itself in the plasma and interstitial SC fluid glucose concentration
      in patients with type 1 diabetes mellitus. METHODS: Eleven subjects with type 1
      diabetes (age 36.5 +/- 9.1 years, HbA1c 7.9 +/- 0.4% [62.8 +/- 2.02 mmol/mol];
      mean +/- standard deviation) were evaluated under hyperinsulinemic euglycemia and
      hypoglycemia. Each subject underwent two randomized crossover clamps with either
      a primed 0.3 (low insulin) or 1 mU/(kg.min) (high insulin) insulin infusion. The
      raw CGM signal was normalized with median preclamp values to obtain a
      standardized measure of the interstitial glucose (IG) concentration before
      statistical analysis. RESULTS: The mean PI concentration was greater in high
      insulin studies (HISs) versus low insulin studies (LISs) (412.89 +/- 13.63 vs.
      177.22 +/- 10.05 pmol/L). During hypoglycemia, glucagon, adrenaline, free fatty
      acids, glycerol, and beta-OH-butyrate were higher in the LIS (P < 0.0001).
      Likewise, the IG concentration was significantly different (P < 0.0001). This was
      due to lower IG concentration than plasma glucose (PG) concentration during the
      euglycemic hyperinsulinemic phases in the HIS. In contrast, no difference was
      observed during hypoglycemia. This was the result of an unchanged PG/IG gradient
      during the entire LIS, while in the HIS, this gradient increased during the
      hyperinsulinemic euglycemia phase. CONCLUSION: Both PI levels and hypoglycemia
      affect the relationship between IG and PG concentration. ClinicalTrials.gov
      Identifier: NCT01714895.

PMID- 29638162
TI  - miR-92b-3p Promotes Colorectal Carcinoma Cell Proliferation, Invasion, and
      Migration by Inhibiting FBXW7 In Vitro and In Vivo.
AB  - microRNA (miR)-92b is an oncogenic miRNA. F-box and WD-40 domain protein 7
      (FBXW7/hCdc4) is a tumor suppressor and a target of miR-92b-3p. This study was
      designed to investigate the effect of miR-92b-3p on colorectal carcinoma (CRC)
      invasion. The expression levels of miR-92b-3p in human HT29, HCT116, and human
      fetal colon (FHC) normal cells were detected. HT29 and HCT116 cells were
      transfected with either miR-92b-3p inhibitor or FBXW7 expression plasmids (pcDNA
      FBXW7) and combination of miR-92b-3p and siRNA-FBXW7. Cell viability, migration,
      invasion, colony formation, cell cycle, and apoptosis in transfected cells were
      detected using corresponding methods. Moreover, the target relationship between
      miR-92b-3p and FBXW7 was verified using dual-luciferase reporter assay. miR-92b
      3p was upregulated in CRC cells in comparison with FHC cells. Then, we
      transfected HT29 and HCT116 cells with miR-92b-3p inhibitor or pcDNA-FBXW7 and
      found decreased cell proliferation, migration, invasion, and colony formation
      ability, as well as the number of upregulated cells at G1 phase of cell cycle and
      cell apoptosis. With the cotransfection of miR-92b-3p inhibitor and siRNA-FBXW7,
      we determined that siRNA-FBXW7 partially attenuated the effect of miR-92b-3p
      inhibitor on cell behaviors. SiRNA-FBXW7 administration to miR-92b-3p inhibitor
      treated cells rebooted cell proliferation, cell migration, invasion, and colony
      formation. miR-92b-3p inhibition prevented CRC proliferation, invasion, and
      migration by upregulating FBXW7, which might suggest the potential role of miR
      92b-3p in colorectal carcinogenesis and metastasis.

PMID- 29638164
TI  - Long Noncoding RNA AK021443 Promotes Cell Proliferation and Migration by
      Regulating Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma Cells.
AB  - Long noncoding RNAs (lncRNAs) were dysregulated in many kinds of cancers,
      including hepatocellular carcinoma (HCC). AK021443, as a novel lncRNA, was found
      to be upregulated in HCC, while its potential value and function are still
      unknown. The pathological changes of liver tissues were observed by hematoxylin
      and eosin staining. The expression levels of AK021443 in HCC tissues and cell
      lines were examined by quantitative real-time polymerase chain reaction (qRT
      PCR). The proliferation ability of AK021443 on HepG2 and Bel-7402 cells was
      assessed by CCK8 and EdU staining assays. The role of AK021443 in HepG2 and Bel
      7402 cell invasion and migration was measured by Transwell and wound healing
      assays. Finally, the expression of epithelial-mesenchymal transition (EMT)
      markers, including E-cadherin, N-cadherin, vimentin, and snail, was investigated
      by qRT-PCR, Western blot, and immunofluorescence. The role of AK021443 in vivo
      was also analyzed. Hepatoma cell nucleus increased in HCC tissues compared with
      normal liver tissues. AK021443 expression was increased in HCC tissues and cell
      lines. Knockdown of AK021443 significantly reduced HepG2 and Bel-7402 cell
      proliferation, invasion, and migration. Furthermore, inhibition of AK021443 in
      HepG2 and Bel-7402 cells significantly repressed EMT ability. Knockdown of
      AK021443 in vivo also significantly inhibited tumor growth with decreased Ki-67
      levels and EMT phenotype in tumor tissues. However, these functions could be
      reversed by overexpression of AK021443. AK021443 significantly controlled HepG2
      and Bel-7402 cell proliferation, colony formation, invasion, and migration by
      repressing EMT, which might provide a potential therapeutic target for HCC
      diagnosis.

PMID- 29638163
TI  - Mining the Virome for Insights into Type 1 Diabetes.
AB  - Type 1 diabetes (T1D) is characterized by the autoimmune destruction of insulin
      producing pancreatic beta cells. Although environmental factors interplay with
      genetic susceptibility to promote immune dysregulation and disease, it remains
      unclear as to which potential environmental factors are causative and not simply
      correlative. Despite many hints that the microbiome can have a profound effect on
      T1D, significant changes in bacterial gut flora and diversity appear to emerge
      only after the detection of early signs of T1D. Surprisingly, we recently found
      significant differences in the gut virome preceding the initial signs of T1D,
      raising the tantalizing possibility that the state of the virome may influence or
      predict whether susceptible individuals progress on the path to disease. The
      challenge will be to discern whether there is likely a causative relationship
      between detected virome differences and T1D.

PMID- 29638165
TI  - Intensified Sampling in Response to a Salmonella Heidelberg Outbreak Associated
      with Multiple Establishments Within a Single Poultry Corporation.
AB  - On June 28, 2013, the Food Safety and Inspection Service (FSIS) was notified by
      the Centers for Disease Control and Prevention (CDC) of an investigation of a
      multistate cluster of illnesses of Salmonella enterica serovar Heidelberg. Since
      case-patients in the cluster reported consumption of a variety of chicken
      products, FSIS used a simple likelihood-based approach using traceback
      information to focus on intensified sampling efforts. This article describes the
      multiphased product sampling approach taken by FSIS when epidemiologic evidence
      implicated chicken products from multiple establishments operating under one
      corporation. The objectives of sampling were to (1) assess process control of
      chicken slaughter and further processing and (2) determine whether outbreak
      strains were present in products from these implicated establishments. As part of
      the sample collection process, data collected by FSIS personnel to characterize
      product included category (whole chicken and type of chicken parts), brand,
      organic or conventional product, injection with salt solutions or flavorings, and
      whether product was skinless or skin-on. From the period September 9, 2013,
      through October 31, 2014, 3164 samples were taken as part of this effort.
      Salmonella percent positive declined from 19.7% to 5.3% during this timeframe as
      a result of regulatory and company efforts. The results of intensified sampling
      for this outbreak investigation informed an FSIS regulatory response and
      corrective actions taken by the implicated establishments. The company noted that
      a multihurdle approach to reduce Salmonella in products was taken, including on
      farm efforts such as environmental testing, depopulation of affected flocks,
      disinfection of affected houses, vaccination, and use of various interventions
      within the establishments over the course of several months.

PMID- 29638167
TI  - Inactivation of Escherichia coli O157:H7 and Salmonella on Fresh Herbs by Plant
      Essential Oils.
AB  - Consumer awareness of fresh herbs and its demand has increased in recent years
      due to health benefits and distinct aroma in prepared food. There are specific
      markets for local growers, especially for organically grown herbs. Shiga
      toxigenic Escherichia coli and Salmonella spp. have been detected and associated
      with foodborne outbreaks from fresh herbs. Limited treatment options are
      available in the processing of fresh herbs to prevent the spread of foodborne
      pathogens. In this study, plant-based essential oils were evaluated on fresh
      herbs for their antimicrobial activities against Salmonella and E. coli O157:H7.
      Fresh herbs (basil, cilantro, dill, parsley, and tarragon) were inoculated with
      cocktails of either Salmonella or E. coli O157:H7 and then dip treated with
      chlorine (50 ppm), cinnamaldehyde (0.3 and 0.5%), and carvacrol (0.1 and 0.3%).
      Control herb samples were dipped in sterile water. Samples were collected on days
      0, 2, 7, and 14 for enumeration of pathogens during 4 degrees C storage. The
      bactericidal efficacy differed with herbs and antimicrobial concentrations.
      Treatments with 0.3% carvacrol or 0.5% cinnamaldehyde reduced E. coli O157:H7 and
      Salmonella by 5 log CFU/g (p > 0.05%) on cilantro and dill leaves from their
      initial inoculum level. Bactericidal efficacy of 0.1% carvacrol and 0.3%
      cinnamaldehyde was significant against Salmonella compared with chlorine on all
      herb leaves. E. coli O157:H7 and Salmonella populations were reduced further
      during storage of treated herbs. There was no visual difference in herbs treated
      with 0.3% cinnamaldehyde or 0.1% carvacrol from control samples. Results indicate
      that 0.3% cinnamaldehyde and 0.1% carvacrol are effective against E. coli O157:H7
      and Salmonella, retain color attributes of fresh herbs, and, therefore, may be an
      alternative wash treatment for fresh herbs.

PMID- 29638166
TI  - Detection, Prevalence, and Pathogenicity of Non-O157 Shiga Toxin-Producing
      Escherichia coli from Cattle Hides and Carcasses.
AB  - Cattle are a major reservoir for Shiga toxin-producing Escherichia coli (STEC)
      and harbor these bacteria in the intestinal tract. The prevalence, concentration,
      and STEC serogroup isolated in cattle varies between individuals. Hide removal at
      slaughter serves as a major point of carcass contamination and ultimately beef
      products. Certain STEC serogroups, such as O26, O45, O103, O111, O121, O145, and
      O157, containing the intestinal adherence factor intimin, pose a large economic
      burden to food producers because of testing and recalls. Human infection with
      STEC can cause illnesses ranging from diarrhea to hemorrhagic colitis and
      hemolytic uremic syndrome, and is commonly acquired through ingestion of
      contaminated foods, often beef products. Previously, most studies focused on O157
      STEC, but there is growing recognition of the importance of non-O157 STEC
      serogroups. This review summarizes detection methods, prevalence, and methods for
      prediction of pathogenicity of non-O157 STEC from cattle hides and carcasses. A
      synthesis of procedures is outlined for general non-O157 STEC and targeted
      detection of specific STEC serogroups. Standardization of sample collection and
      processing procedures would allow for more robust comparisons among studies.
      Presence of non-O157 STEC isolated from cattle hides and carcasses and specific
      factors, such as point of sample collection and season, are summarized. Also,
      factors that might influence STEC survival on these surfaces, such as the
      microbial population on hides and microbial adherence genes, are raised as topics
      for future investigation. Finally, this review gives an overview on studies that
      have used genetic and cell-based methods to identify specific phenotypes of non
      O157 STEC strains isolated from cattle to assess their risk to human health.

PMID- 29638168
TI  - Maintenance of Carbapenemase-Producing Enterobacteriaceae in a Farrow-to-Finish
      Swine Production System.
AB  - Carbapenemase-producing Enterobacteriaceae (CPE) threaten both agriculture and
      public health. While carbapenems are restricted in food-producing animals, other
      beta-lactams, such as ceftiofur, are frequently applied in livestock. While the
      relationship is not fully elucidated, ceftiofur use may provide selective
      pressure that promotes carbapenem resistance. Recently reported in U.S.
      livestock, plasmid-mediated CPE are also present in livestock in Europe and Asia.
      We previously reported the rare carbapenemase gene, blaIMP-64, in the environment
      of a large farrow-to-finish swine operation. To better understand CPE in this
      swine production system, in 2016 we followed a cohort of 350+ pigs over 5 months
      from late sow gestation to the final finishing phase. We screened both
      environmental and fecal samples for CPE using our selective enrichment protocol,
      with resulting phenotypic CPE isolates further characterized. Of 55 environmental
      and 109 sow fecal samples collected from a farrowing barn on our initial visit,
      35 (64%) environmental and 15 (14%) sow fecal samples yielded isolates of
      multiple Enterobacteriaceae species carrying the metallo-beta-lactamase gene
      blaIMP-64 on an IncQ plasmid. The frequency of IMP-64-positive environmental (n =
      32), sow fecal (n = 30), and piglet fecal swab (n = 120) samples was highest for
      all groups when the market pig cohort was between 1 and 10 days, with observed
      prevalence of 97%, 28%, and 18%, respectively. After weaning, blaIMP-64 was
      detected in a single environmental sample from a nursery pen, with no CPE
      recovered in the finishing phase. Used in U.S. swine production to treat and
      control disease, ceftiofur is administered to piglets on this farm at birth, with
      males receiving a second dose at castration (~day 7). Once introduced into animal
      agriculture, the common use of ceftiofur may provide the selection pressure
      required for CPE dissemination throughout large, intensively managed food animal
      populations housed in animal-dense environments.

PMID- 29638169
TI  - Characterization of Staphylococcus aureus Isolated from Food Products in Western
      Algeria.
AB  - The current study aimed to characterize Staphylococcus aureus isolates from
      foodstuffs collected from western Algeria. A total of 153 S. aureus isolates from
      various raw and processed foods were obtained and identified using matrix
      assisted laser desorption and ionization time-of-flight mass spectrometry.
      Isolates were characterized by antimicrobial susceptibility testing and toxin
      gene detection. Methicillin-resistant Staphylococcus aureus (MRSA) isolates were
      identified by detection of the mecA gene and characterized by staphylococcal
      cassette chromosome mec (SCCmec) typing. We found that 30.9% (153/495) of food
      samples were contaminated with S. aureus. Thirty-three (21.5%) S. aureus isolates
      were identified as MRSA, and 16.9% (26/153) carried the mecA gene. Three SCCmec
      types were identified of which type IV was the most common (69.2%) followed by
      type V (15.3%) and type II (7.6%). Two MRSA isolates were not typable with SCCmec
      typing. None of the examined isolates harbored mecC. Furthermore, 14.3% (22/153)
      of the isolates were toxigenic S. aureus. The cytotoxin gene pvl was detected in
      11.1% of the S. aureus isolates. This gene was more commonly detected (76.4%) in
      MRSA isolates than in methicillin-suceptible Staphylococcus aureus (MSSA)
      isolates. The tsst-1 gene coding for toxic shock syndrome toxin was isolated
      rarely (3.2%) and only in MSSA isolates. According to disk diffusion test
      results, 70 isolates were resistant to only one antimicrobial drug, and 51
      (33.3%) isolates were multidrug resistant. Other 32 isolates were susceptible to
      all antibiotics. Our study highlights, for the first time, a high prevalence of
      multidrug-resistant S. aureus isolates carrying pvl or tsst-1 found in food
      products in Algeria. The risk of MRSA transmission through the food chain cannot
      be disregarded, particularly in uncooked foods.

PMID- 29638170
TI  - Seven Salmonella Typhimurium Outbreaks in Australia Linked by Trace-Back and
      Whole Genome Sequencing.
AB  - Salmonella Typhimurium is a common cause of foodborne illness in Australia. We
      report on seven outbreaks of Salmonella Typhimurium multilocus variable-number
      tandem-repeat analysis (MLVA) 03-26-13-08-523 (European convention 2-24-12-7
      0212) in three Australian states and territories investigated between November
      2015 and March 2016. We identified a common egg grading facility in five of the
      outbreaks. While no Salmonella Typhimurium was detected at the grading facility
      and eggs could not be traced back to a particular farm, whole genome sequencing
      (WGS) of isolates from cases from all seven outbreaks indicated a common source.
      WGS was able to provide higher discriminatory power than MLVA and will likely
      link more Salmonella Typhimurium cases between states and territories in the
      future. National harmonization of Salmonella surveillance is important for
      effective implementation of WGS for Salmonella outbreak investigations.

PMID- 29638171
TI  - Campylobacter Prevalence and Quinolone Susceptibility in Feces of Preharvest
      Feedlot Cattle Exposed to Enrofloxacin for the Treatment of Bovine Respiratory
      Disease.
AB  - Campylobacter spp. can be pathogenic to humans and often harbor antimicrobial
      resistance genes. Data on resistance in relation to fluoroquinolone use in beef
      cattle are scarce. This cross-sectional study of preharvest cattle evaluated
      Campylobacter prevalence and susceptibility to nalidixic acid and ciprofloxacin
      in feedlots that previously administered a fluoroquinolone as primary treatment
      for bovine respiratory disease. Twenty fresh fecal samples were collected from
      each of 10 pens, in each of five feedlots, 1-2 weeks before harvest. Feces were
      cultured for Campylobacter using selective enrichment and isolation methods.
      Genus and species were confirmed via PCR. Minimum inhibitory concentrations
      (MICs) of ciprofloxacin and nalidixic acid were determined using a micro-broth
      dilution method and human breakpoints. Antimicrobial use within each pen was
      recorded. Data were analyzed using generalized linear mixed-models (prevalence)
      and survival analysis (MICs). Overall, sample-level prevalence of Campylobacter
      was 27.2% (272/1000) and differed significantly among feedlots (p < 0.01).
      Campylobacter coli was the most common species (55.1%; 150/272), followed by
      Campylobacter hyointestinalis (42.6%; 116/272). Within-pen prevalence was not
      significantly associated with the number of fluoroquinolone treatments, sex, body
      weight, or metaphylaxis use, but was associated with the number of days cattle
      were in the feedlot (p = 0.03). The MICs for the majority of Campylobacter
      isolates were above the breakpoints for nalidixic acid (68.4%; 175/256) and for
      ciprofloxacin (65.6%; 168/256). Distributions of MICs for nalidixic acid (p <=
      0.01) and ciprofloxacin (p <= 0.05) were significantly different among feedlots,
      and by Campylobacter species. However, fluoroquinolone treatments, sex, body
      weight, days on feed, and metaphylaxis were not significantly associated with MIC
      distributions within pens. We found no evidence that the number of
      fluoroquinolone treatments within feedlot pens significantly affected the within
      pen fecal prevalence or quinolone susceptibilies of Campylobacter in feedlots
      that used a fluoroquinolone as primary treatment for bovine respiratory disease.

PMID- 29638172
TI  - Capturing public interest toward new tools for controlling human immunodeficiency
      virus (HIV) infection exploiting data from Google Trends.
AB  - Human immunodeficiency virus vaccination and pre-exposure prophylaxis represent
      two different emerging preventive tools. Google Trends was used to assess the
      public interest toward these tools in terms of digital activities. Worldwide web
      searches concerning the human immunodeficiency virus vaccine represented 0.34
      percent, 0.03 percent, and 46.97 percent of human immunodeficiency virus,
      acquired immune deficiency syndrome, and human immunodeficiency virus/acquired
      immune deficiency syndrome treatment-related Google Trends queries, respectively.
      Concerning temporal trends, digital activities were shown to increase from 0
      percent as of 1 January 2004 percent to 46 percent as of 8 October 2017 with two
      spikes observed in May and July 2012, coinciding with the US Food and Drug
      Administration approval. Bursts in search number and volume were recorded as
      human immunodeficiency virus vaccine trials emerged. This search topic has
      decreased in the past decade in parallel to the increase in Truvada-related
      topics. Concentrated searches were noticed among African countries with high
      human immunodeficiency virus/acquired immune deficiency syndrome prevalence.
      Stakeholders should take advantage of public interest especially in preventive
      medicine in high disease burden countries.

PMID- 29638174
TI  - Preliminary evaluation of an adolescent positive health measurement scale: a
      salutogenic health promotion approach.
AB  - Health measurement tools typically assess indicators of poor health by
      identifying the absence, or presence, of disease and risk factors. This article
      describes development and validation of the first instrument for measurement of
      adolescent engagement in positive health promoting actions from a salutogenic
      approach. This cross-sectional study of 406 youths 14-16 years old tested the
      validity and reliability of the Salutogenic Wellness Promotion Scale for
      Adolescents (SWPS-Adol) and examined the extent to which SWPS-Adol positively
      correlated with and was able to predict perceived health among this population.
      Findings indicated that SWPS-Adol had good internal consistency ( alpha = 0.84,
      subscales alpha = 0.70), a multi-dimensional structure (physical, emotional,
      social, vocational and spiritual), and was positively correlated with perceived
      health ( r = 0.37, p < 0.001). The SWPS-Adol total score also showed significant
      positive correlations with the physical ( p <= 0.001), emotional ( p < 0.001),
      social ( p < 0.001) and vocational ( p < 0.039) dimensions. The more adolescents
      engaged in positive behaviors, the better their perceived health. The SWPS-Adol
      tool provides positive health data to guide adolescent health programs and health
      curricula, to inform health professionals and policy makers about how positive
      health actions enhance health and community wellness.

PMID- 29638173
TI  - Differential expression of hemoglobin receptor, HmbR, between carriage and
      invasive isolates of Neisseria meningitidis contributes to virulence: lessons
      from a clonal outbreak.
AB  - Carriage and invasion balance in the pathogenesis of Neisseria meningitidis was
      analyzed during a recent clonal outbreak of meningococcal B in Normandy, France,
      that offered the opportunity to compare six isolates undistinguable by
      conventional typing (B:14:P1.7,16:F3-3/ST-32) isolated from invasive disease or
      pharyngeal asymptomatic carriage. Data from animal model (transgenic mice
      rendered susceptible to N. meningitidis infection) showed an absence of virulence
      for two non-capsulated carriage isolates, an intermediate virulence for two
      capsulated carriage isolates and a marked virulence for two capsulated invasive
      isolates. This differential pathogenesis well correlated with whole genome
      sequencing analysis that clustered both isolates of each group together, forming
      their own arm within the Norman cluster. Gene-by-gene analysis specified that
      genes involved in iron acquisition were among the elements differentially
      represented in cluster of invasive isolates compared to cluster of capsulated
      carriage isolates. The hemoglobin receptor encoding gene hmbR was in an ON-phase
      in the capsulated invasive isolates while carriage capsulated isolates were in an
      OFF-phase. An ON-phase variant of a capsulated carriage isolate showed enhanced
      virulence. These data underline the role of phase variation (ON/OFF) of HmbR in
      the balance between disease isolates/carriage isolates.

PMID- 29638175
TI  - Measuring functional, interactive and critical health literacy of Chinese
      secondary school students: reliable, valid and feasible?
AB  - Health literacy is an increasingly important topic in the global context. In
      mainland China, health literacy measures mainly focus on health knowledge and
      practices or on the functional domain for adolescents. However, little is known
      about interactive and critical domains. This study aimed to adopt a skills-based
      and three-domain (functional, interactive and critical) instrument to measure
      health literacy in Chinese adolescents and to examine the status and determinants
      of each domain. Using a systematic review, the eight-item Health Literacy
      Assessment Tool (HLAT-8) was selected and translated from English to Chinese (c
      HLAT-8). Following the translation process, a cross-sectional study was conducted
      in four secondary schools in Beijing, China. A total of 650 students in Years 7-9
      were recruited to complete a self-administered questionnaire that assessed socio
      demographics, self-efficacy, social support, school environment, community
      environment and health literacy. Results showed that the c-HLAT-8 had
      satisfactory reliability (Cronbach's alpha = 0.79; intra-class correlation
      coefficient = 0.72) and strong validity (translation validity index (TVI) >=0.95;
      chi2/ df = 3.388, p < 0.001; comparative fit index = 0.975, Tucker and Lewis's
      index of fit = 0.945, normed fit index = 0.965, root mean error of approximation
      = 0.061; scores on the c-HLAT-8 were moderately correlated with the Health
      Literacy Study-Taiwan, but weakly with the Newest Vital Sign). Chinese students
      had an average score of 26.37 (+/-5.89) for the c-HLAT-8. When the determinants
      of each domain of health literacy were examined, social support was the strongest
      predictor of interactive and critical health literacy. On the contrary, self
      efficacy and school environment played more dominant roles in predicting
      functional health literacy. The c-HLAT-8 was demonstrated to be a reliable, valid
      and feasible instrument for measuring functional, interactive and critical health
      literacy among Chinese students. The current findings indicate that increasing
      self-efficacy, social support and creating supportive environments are important
      for promoting health literacy in secondary school settings in China.

PMID- 29638176
TI  - Laparoscopic Treatment of the Isolated Renal Hydatid Cyst: Long-Term Outcomes
      from a Single Institution.
AB  - OBJECTIVE: To determine the effectiveness of treatment via laparoscopic approach
      and to present the long-term outcomes in patients with isolated renal hydatid
      cyst. MATERIALS AND METHODS: We reviewed the data of 11 patients who underwent
      laparoscopic treatment for isolated renal hydatid cyst between March 2004 and
      January 2017. Demographic characteristics and clinical, laboratory, and
      radiological findings of cases were examined. Mann-Whitney U and t-test were used
      in statistical analysis. RESULTS: The mean age of the patients was 36.7 years (25
      51). The common complaint of the patients was lumbar pain and 9 patients had a
      palpable mass. It was identified that serologic evaluation of Echinococcus
      granulosus was positive in 5 patients. The mean cyst size was determined as 72 mm
      (40-150). The mean operation time was 128 minutes (120-150) while the length of
      hospital stay was 4 days (3-13). Perioperative major complication was not
      observed in any of the patients. The levels of hematocrit and creatinine were
      measured, 37.8 (26-43) and 0.93 (0.5-1.3), respectively, in the postoperative
      period, while these levels were 39 (26-45) and 0.90 (0.5-1.3) in the preoperative
      period and there was no statistically significant difference (P > .05). The mean
      follow-up time was 84 months (40-166). No relapses were observed in any patients.
      CONCLUSIONS: The treatment of renal hydatid cyst disease with laparoscopic
      approach is a safe and effective method. There was no recurrence in any of the
      patients in the long-term period. Further studies including a large series of
      patients are needed.

PMID- 29638178
TI  - Commentary on: Social versus biological psychiatry: It's time for integration!

PMID- 29638177
TI  - Phenotypic changes associated with Colistin resistance due to Lipopolysaccharide
      loss in Acinetobacter baumannii.
AB  - Acinetobacter baumannii can acquire resistance to colistin via complete loss of
      lipopolysaccharide (LPS) biosynthesis due to mutations in the lpxA, lpxC and lpxD
      genes. However, although colistin is increasingly being used for the treatment of
      multidrug resistant infections, very few A. baumannii clinical isolates develop
      colistin resistance through loss of LPS biosynthesis. This may suggest that LPS
      loss affects virulence traits that play a role in the transmission and
      pathogenesis of A. baumannii. In this study we characterize multiple virulence
      phenotypes of colistin resistant, LPS-deficient derivatives of the ATCC 19606
      strain and five multidrug resistant clinical isolates and their colistin
      resistant, LPS-deficient derivatives. Our results indicate that LPS loss results
      in growth defects compared to the parental strain in vitro both in laboratory
      media and human serum (competition indices of 0.58 and 7.0 * 10-7, respectively)
      and reduced ability to grow and disseminate in vivo (competition index 6.7 * 10
      8). Infection with the LPS-deficient strain resulted in lower serum levels of pro
      inflammatory cytokines TNF-alpha and IL-6 compared to the parent strain, and was
      less virulent in a mouse model of disseminated sepsis. LPS loss also
      significantly affected biofilm production, surface motility, growth under iron
      limitation and susceptibility to multiple disinfectants used in the clinical
      setting. These results demonstrate that LPS loss has a significant effect on
      multiple virulence traits, and may provide insight into the low incidence of
      colistin resistant strains lacking LPS that have been reported in the clinical
      setting.

PMID- 29638179
TI  - Integration and beyond.

PMID- 29638180
TI  - Integration is not necessarily at odds with reductionism.

PMID- 29638181
TI  - Integrating social and biological psychiatry: A forensic perspective.

PMID- 29638182
TI  - Social versus biological psychiatry: It's time for integration! Commentary by
      Nick Rose.

PMID- 29638183
TI  - The Birth and Death of Platelets in Health and Disease.
AB  - Blood platelets are involved in a wide range of physiological responses and
      pathological processes. Recent studies have considerably advanced our
      understanding of the mechanisms of platelet production and clearance, revealing
      new connections between the birth and death of these tiny, abundant cells. Key
      insights have also been gained into how physiological challenges such as
      inflammation, infection, and chemotherapy can affect megakaryocytes, the cells
      that produce platelets.

PMID- 29638185
TI  - Glucose Lowering Strategies for Cardiac Benefits: Pathophysiological Mechanisms.
AB  - Recent trials in Type 2 diabetes (T2D) have shown cardiovascular benefits with
      specific GLP-1 receptor agonists and SGLT2 inhibitors. We discuss the landscape
      of outcome trials in T2D from a pathophysiology viewpoint, review current
      knowledge gaps in underlying mechanisms, propose a caloric fuel routing
      hypothesis, and highlight areas of future research.

PMID- 29638184
TI  - Impaired Autophagy in Motor Neurons: A Final Common Mechanism of Injury and
      Death.
AB  - Autophagy is a cellular digestion process that contributes to cellular
      homeostasis and adaptation by the elimination of proteins and damaged organelles.
      Evidence suggests that dysregulation of autophagy plays a role in
      neurodegenerative diseases, including motor neuron disorders. Herein, we review
      emerging evidence indicating the roles of autophagy in physiological motor neuron
      processes and its function in specific compartments. Moreover, we discuss the
      involvement of autophagy in the pathogenesis of motor neuron diseases, including
      spinal cord injury and aging, and recent developments that offer promising
      therapeutic approaches to mitigate effects of dysregulated autophagy in health
      and disease.

PMID- 29638188
TI  - Production Practice During Language Learning Improves Comprehension.
AB  - Language learners often spend more time comprehending than producing a new
      language. However, memory research suggests reasons to suspect that production
      practice might provide a stronger learning experience than comprehension
      practice. We tested the benefits of production during language learning and the
      degree to which this learning transfers to comprehension skill. We taught
      participants an artificial language containing multiple linguistic dependencies.
      Participants were randomly assigned to either a production- or a comprehension
      learning condition, with conditions designed to balance attention demands and
      other known production-comprehension differences. After training, production
      learning participants outperformed comprehension-learning participants on
      vocabulary comprehension and on comprehension tests of grammatical dependencies,
      even when we controlled for individual differences in vocabulary learning. This
      result shows that producing a language during learning can improve subsequent
      comprehension, which has implications for theories of memory and learning,
      language representations, and educational practices.

PMID- 29638189
TI  - Acoustics of ping-pong: Vibroacoustic analysis of table tennis rackets and balls.
AB  - The sound resulting from the impact of a table tennis racket and ball can
      influence a player's perception of equipment quality in addition to providing
      clues to personal performance. This study explores the vibrational modes of both
      racket and ball and how those modes contribute to the impact sound. Experimental
      modal analysis reveals that the racket exhibits a large number of structural
      vibration modes typical of elliptical plates. Acoustic analysis reveals that two
      of those structural modes dominate the sound produced by the ball-paddle impact.
      The rubber padding provides some damping and a significant mass loading to the
      racket vibrations. The hollow cellulose nitrate balls exhibit vibrational modes
      typical of a hollow spherical shell, starting with frequencies around 5920 Hz.
      Experimental frequencies confirm theoretical and computational models. However,
      the contact time between racket and ball is long enough that the lowest acoustic
      modes of the ball do not contribute to the radiated sound. Instead, acoustic
      analysis suggests that the ball appears to radiate sound at a much higher
      frequency sound (8.5-12 kHz) most likely due to snap-through after buckling
      common to spherical shells undergoing deformation while impacting a rigid surface
      at high speeds.

PMID- 29638186
TI  - Helicobacter suis binding to carbohydrates on human and porcine gastric mucins
      and glycolipids occurs via two modes.
AB  - Helicobacter suis colonizes the stomach of most pigs and is the most prevalent
      non-Helicobacter pylori Helicobacter species found in the human stomach. In the
      human host, H. suis contributes to the development of chronic gastritis, peptic
      ulcer disease and MALT lymphoma, whereas in pigs it is associated with gastritis,
      decreased growth and ulcers. Here, we demonstrate that the level of H. pylori and
      H. suis binding to human and pig gastric mucins varies between individuals with
      species dependent specificity. The binding optimum of H. pylori is at neutral pH
      whereas that of H. suis has an acidic pH optimum, and the mucins that H. pylori
      bind to are different than those that H. suis bind to. Mass spectrometric
      analysis of mucin O-glycans from the porcine mucin showed that individual
      variation in binding is reflected by a difference in glycosylation; of 109
      oligosaccharide structures identified, only 14 were present in all examined
      samples. H. suis binding to mucins correlated with glycans containing sulfate,
      sialic acid and terminal galactose. Among the glycolipids present in pig stomach,
      binding to lactotetraosylceramide (Galbeta3GlcNAcbeta3Galbeta4Glcbeta1Cer) was
      identified, and adhesion to Galbeta3GlcNAcbeta3Galbeta4Glc at both acidic and
      neutral pH was confirmed using other glycoconjugates. Together with that H. suis
      bound to DNA (used as a proxy for acidic charge), we conclude that H. suis has
      two binding modes: one to glycans terminating with Galbeta3GlcNAc, and one to
      negatively charged structures. Identification of the glycan structures H. suis
      interacts with can contribute to development of therapeutic strategies
      alternative to antibiotics.

PMID- 29638187
TI  - mirRICH, a simple method to enrich the small RNA fraction from over-dried RNA
      pellets.
AB  - Techniques to isolate the small RNA fraction (<200nt) by column-based methods are
      commercially available. However, their use is limited because of the relatively
      high cost. We found that large RNA molecules, including mRNAs and rRNAs, are
      aggregated together in the presence of salts when RNA pellets are over-dried.
      Moreover, once RNA pellets are over-dried, large RNA molecules are barely soluble
      again during the elution process, whereas small RNA molecules (<100nt) can be
      eluted. We therefore modified the acid guanidinium thiocyanate-phenol-chloroform
      (AGPC)-based RNA extraction protocol by skipping the 70% ethanol washing step and
      over-drying the RNA pellet for 1 hour at room temperature. We named this novel
      small RNA isolation method "mirRICH." The quality of the small RNA sequences was
      validated by electrophoresis, next-generation sequencing, and quantitative PCR,
      and the findings support that our newly developed column-free method can
      successfully and efficiently isolate small RNAs from over-dried RNA pellets.

PMID- 29638190
TI  - Long-term effects of the 11+ warm-up injury prevention programme on physical
      performance in adolescent male football players: a cluster-randomised controlled
      trial.
AB  - This study examined the long-term effects of the 11+ on physical performance in
      adolescent male football (soccer) players. Eighty-two 14- to 16-year-old male
      football players (11+ = 42 players, control = 40 players) participated. Teams
      were randomised to control (CON) and intervention (INT) groups. INT applied the
      11+ injury prevention programme for 30 weeks at least twice a week as a warm-up.
      CON performed their standard warm-up. Motor performance tests were conducted 1
      week prior and 1 week after the competition season. We used magnitude-based
      inferences and linear mixed-effects models to analyse performance test results.
      INT showed superior results compared to CON in the vertical jump height 7.5% (95%
      CI 4.4%, 10.7%), the Bosco 15-s-jump test 7.2% (95%-CI 2.2%, 12.4%), and the
      Illinois agility test -2.6% (95%-CI -4.1%, -1.1%). Possibly beneficial effects in
      favour of INT were found in the 9.1 m sprint test -3.1% (95%-CI -6.1%, 0.1%).
      Possibly harmful effects (i.e. in favour of CON) were observed in the dribbling
      test 2.8% (95%-CI -0.8%, 6.4%). The 11+ warm-up programme can improve different
      performance measures in football players. Coaches might implement additional
      dribbling drills next to the 11+ to achieve improvements observed in dribbling
      ability when using a regular warm-up programme.

PMID- 29638191
TI  - Shifting views and building bonds: Narratives of internationally adopted children
      about their dual culture.
AB  - American literature on international adoption suggests that adoptees' pride in
      the culture of their birth country improves their self-esteem and helps them to
      cope with experiences of racism. Parents are therefore encouraged to teach their
      adopted children multicultural skills to improve their psychological well-being.
      French psychologists, on the contrary, suggest that adoptees should feel fully
      members of their adoptive country and families. These practices shed light on the
      respective multicultural and universalist paradigms in the US and France. Few
      papers, however, consider the opinions of adoptees. This study explores
      internationally adopted children raised in France and their spontaneous curiosity
      about their birth country. The present study used semi-structured interviews with
      19 adoptees aged 8-18 years old, to explore their attitudes towards the culture
      of their birth country. Transcripts of recorded interviews were analyzed
      according to interpretative phenomenological analysis. While there was striking
      consistency of interest in birth countries, adoptees' expression of curiosity
      varied across time. Children described distinctive goals: knowing more about
      their history, finding relatives, becoming a multicultural citizen, or simply
      helping people. Their parents' involvement was thus seen as helpful, but adoptees
      stress the need to feel ready and may prefer independent ways of learning about
      their birth country. Adoptees' multiple feelings of belonging derive not only
      from multicultural training but from a lifelong construction of self.
      Professionals and parents may need to adapt to adoptees' individual development,
      distinctive time frames, and ways of learning to provide better support to them.

PMID- 29638192
TI  - Quality of life and communication in orthognathic treatment.
AB  - OBJECTIVE: The primary aim was to determine what, if any, relationships exist
      between communication and quality of life in patients receiving orthognathic
      treatment since this has not been explored. A secondary aim was to compare the
      Quality of Life (QoL) of a pre-treatment sample with those at 2 years post
      surgery. DESIGN: A cross-sectional questionnaire method was used. SETTING:
      Outpatient clinics providing orthognathic treatment at four UK hospital sites.
      PARTICIPANTS: Two separate samples of pre-treatment (n = 73) and 2-year post
      surgery (n = 78) patients participated in the study. METHODS: At clinic
      appointments, all eligible patients were invited to complete the Orthognathic
      Quality of Life Questionnaire (OQLQ), a previously validated condition-specific
      quality of life measure. At the same time, participants at the 2-year post
      surgery stage also completed a second short questionnaire, the Communication
      Assessment Tool-Team (CAT-T), where they rated the quality of communication they
      had received during treatment. RESULTS: One hundred and fifty-one complete
      responses were received. The average age was 24.5 years (S.D. 9.77) and the
      majority (67%) were female in both groups. Statistically significant associations
      were found between QoL and quality of communication in the treated sample.
      Findings also showed a comparatively poorer QoL for the pre-treatment
      participants. This reduced QoL was more pronounced in females than males for all
      aspects except dentofacial appearance. CONCLUSIONS: There was an improvement in
      QoL for patients at 2 years post-surgery compared to pre-treatment. There is an
      association between QoL and quality of communication as reported by participants
      at 2 years post-surgery. These novel findings are similar to outcomes in other
      patient settings such as oncology, but further investigation is required to
      establish the direction of cause and effect.

PMID- 29638193
TI  - Maximizing the Translational Yield of mRNA Therapeutics by Minimizing 5'-UTRs.
AB  - The 5'-untranslated region (5'-UTR) of mRNA contains structural elements, which
      are recognized by cell-specific RNA-binding proteins, thereby affecting the
      translation of the molecule. The activation of an innate immune response upon
      transfection of mRNA into cells is reduced when the mRNA comprises chemically
      modified nucleotides, putatively by altering the secondary structure of the
      molecule. Such alteration in the 5'-UTR in turn may affect the functionality of
      mRNA. In this study, we report on the impact of seven synthetic minimalistic 5'
      UTR sequences on the translation of luciferase-encoding unmodified and different
      chemically modified mRNAs upon transfection in cell culture and in vivo. One
      minimalistic 5'-UTR, consisting of 14 nucleotides combining the T7 promoter with
      a Kozak consensus sequence, yielded similar or even higher expression than a 37
      nucleotides human alpha-globin 5'-UTR containing mRNA in HepG2 and A549 cells.
      Furthermore, also the kind of modified nucleotides used in in vitro
      transcription, affected mRNA translation when using different translation
      regulators (Kozak vs. translation initiator of short UTRs). The in vitro data
      were confirmed by bioluminescence imaging of expression in mouse livers, 6 h
      postintravenous injection of a lipidoid nanoparticle-formulated RNA in female
      Balb/c mice. Luciferase measurements from liver and spleen showed that minimal 5'
      UTRs (3 and 7) were either equally effective or better than human alpha-globin 5'
      UTR. These findings were confirmed with a human erythropoietin (hEPO)-encoding
      mRNA. Significantly, higher levels of hEPO could be quantified in supernatants
      from A549 cells transfected with minimal 5'-UTR7 containing RNA when compared to
      commonly used benchmarks 5'-UTRs. Our results demonstrate the superior potential
      of synthetic minimalistic 5'-UTRs for use in transcript therapies.

PMID- 29638194
TI  - The role of novel cytokines in inflammation: Defining peripheral artery disease
      among patients with coronary artery disease.
AB  - Coronary artery disease (CAD) patients with concomitant peripheral artery disease
      (PAD) experience more extensive and calcified atherosclerosis, greater lesion
      progression and more common coronary events compared to patients with CAD only.
      To characterize the distinct features of this aggressive atherosclerotic disease,
      we studied novel cytokines that code different stages of atherogenesis. One
      hundred and eighty consecutive subjects (60 patients into each group of CAD+PAD,
      CAD and controls) were recruited among patients with stable angina pectoris
      scheduled for coronary angiography. An ankle-brachial index (ABI) <=0.9 was
      determined as occlusive PAD. Fasting serum tumor necrosis factor (TNF)-like
      antigen 1A (TL1A) and its receptor death receptor 3 (DR3), NOGO-B (reticulon 4B)
      and its receptor NUS1, high-sensitivity C-reactive protein (hsCRP), A disintegrin
      and metalloproteinase with thrombospondin motifs (ADAMTS) 1, 4, 5 and interleukin
      (IL) 6 levels were determined. Serum hsCRP and DR3/TL1A concentrations were
      similar and higher than controls in the CAD and CAD+PAD groups. Levels of NOGO-B
      and its receptor NUS1 were increased and ADAMTS-5 was decreased in patients with
      CAD+PAD. Independent predictors of ABI in multivariate analysis were smoking (B =
      -0.13, p = 0.04), NUS1 (B = -0.88, p < 0.001), ADAMTS-5 (B = 0.63, p < 0.001) and
      SYNTAX score (B = -0.26, p < 0.001). Similarly, smoking (OR = 5.5, p = 0.019),
      SYNTAX score (OR = 1.2, p < 0.001), NUS1 (OR = 14.4, p < 0.001), ADAMTS-5 (OR =
      1.1, p < 0.001) and age (OR = 1.1, p = 0.042) independently predicted the
      involvement of peripheral vasculature in logistic regression. The diagnostic
      performance of these cytokines to discriminate CAD+PAD were AUC 0.79 ( p < 0.001)
      for NUS1 and 0.37 ( p = 0.013) for ADAMTS-5. We report herein that circulating
      cytokines can give clues to the ongoing atherosclerotic process and the extent of
      vascular involvement in which distinct features of ADAMTS-5 and NUS1 make them
      promising cytokines for future research.

PMID- 29638195
TI  - Editorial: O-specific polysaccharide confers lysozyme resistance to
      extraintestinal pathogenic Escherichia coli.

PMID- 29638196
TI  - Synthesis of Patterned Vertically Aligned Carbon Nanotubes by PECVD Using
      Different Growth Techniques: A Review.
AB  - Immense development has been taken place not only to increase the bulk
      production, repeatability and yield of carbon nanotubes (CNTs) in last 25 years
      but preference is also given to acknowledge the basic concepts of nucleation and
      growth methods. Vertically aligned carbon nanotubes (VAC-NTs) are forest of CNTs
      accommodated perpendicular on a substrate. Their exceptional chemical and
      physical properties along with sequential arrangement and dense structure make
      them suitable in various fields. The effect of different type of selected
      substrate, carbon precursor, catalyst and their physical and chemical status,
      reaction conditions and many other key parameters have been thoroughly studied
      and analysed. The aim of this paper is to specify the trend and summarize the
      effect of key parameters instead of only presenting all the experiments reported
      till date. The identified trends will be compared with the recent observations on
      the growth of different types of patterned VACNTs. In this review article, we
      have presented a comprehensive analysis of different techniques to precisely
      determine the role of different parameters responsible for the growth of
      patterned vertical aligned carbon nanotubes. We have covered various techniques
      proposed in the span of more than two decades to fabricate the different
      structures and configurations of carbon nanotubes on different types of
      substrates. Apart from a detailed discussion of each technique along with their
      specific process and implementation, we have also provided a critical analysis of
      the associated constraints, benefits and shortcomings. To sum it all for easy
      reference for researchers, we have tabulated all the techniques based on certain
      main key factors. This review article comprises of an exhaustive discussion and a
      handy reference for researchers who are new in the field of synthesis of CNTs or
      who wants to get abreast with the techniques of determining the growth of VACNTs
      arrays.

PMID- 29638197
TI  - The Development of Newborn Porcine Models for Evaluation of Tissue-Engineered
      Small Intestine.
AB  - Short bowel syndrome (SBS) is a major cause of morbidity and mortality in the
      pediatric population, for which treatment options are limited. To develop novel
      approaches for the treatment of SBS, we now focus on the development of a tissue
      engineered intestine (also known as an "artificial intestine"), in which
      intestinal stem cells are cultured onto an absorbable bioscaffold, followed by
      implantation into the host. To enhance the translational potential of these
      preclinical studies, we have developed three clinically relevant models in
      neonatal piglets, which approximate the size of the human infant and were
      evaluated after implantation and establishment of intestinal continuity over the
      long term. The models included (1) a staged, multioperation approach; (2) a
      single operation with a de-functionalized loop of small intestine; and (3) a
      single operation with an intestinal bypass. The first model had complications
      related to multiple operations in a short time period, including surgical site
      infections and wound hernias. The second model avoided wound complications, but
      was associated with high ostomy output, local skin breakdown, and systemic
      dehydration with associated electrolyte imbalances. The third model was the most
      effective, although resulted in stoma prolapse. In summary, we have now developed
      and evaluated three operative methods for the long-term evaluation of the
      artificial intestine in the piglet, and conclude that a single operation with a
      de-functionalized loop of small intestine may be an optimal approach for
      evaluation over the long term.

PMID- 29638198
TI  - Utilization of cues in action anticipation in table tennis players.
AB  - By manipulating the congruency between body kinematics and subsequent ball
      trajectory, this study investigated the anticipation capabilities of regional
      level, college-level, and novice table tennis players using a full video
      simulation occluder paradigm. Participants watched footage containing congruent,
      incongruent, or no ball trajectory information, to predict the landing point of
      the ball. They were required to choose between two potential locations to make
      their prediction. Percent accuracy and relevant indexes (d-prime, criterion,
      effect size) were calculated for each condition. Results indicated that
      experienced table tennis players (both regional and college players) were
      superior to novices in the ability to anticipate ball trajectory using kinematic
      information, but no difference was found between regional-level and college-level
      players. The findings of this study further demonstrate the superior anticipation
      ability of experienced table tennis players. Furthermore, the present result
      suggests that there may be a certain "baseline" level of motor experience in
      racquet sports for effective action anticipation, while the addition of further
      motor experience does not appear to assist direction anticipation.

PMID- 29638199
TI  - The effect of air exposure on leucocyte and cytokine activation in an in-vitro
      model of cardiotomy suction.
AB  - INTRODUCTION: Cardiopulmonary bypass (CPB) is known to cause a systemic
      inflammatory and immune response. OBJECTIVE: An in-vitro model of cardiotomy
      suction was designed to quantify the effects of incrementally increased air-blood
      exposure on leucocyte marker CD11b and cytokine activation in two common
      anticoagulants, heparin and citrate. METHODS: Fresh human blood was exposed to
      increasing amounts of air flow for ten minutes. Leucocyte and cytokine levels
      were measured prior to and after ten minutes of air flow. Cytokine levels were
      also measured after air exposure when incubated for 24 hours at 37oC. RESULTS:
      Leucocyte activation, measured by CD11b, was elevated between baseline and air
      flow rates up to 50 mL/min. After 10 minutes of air exposure, no measured
      cytokine levels were elevated. After 24 hours of incubation, cytokine levels of
      TNFalpha, IL-10, IL-6, and IL-8 were elevated. However, only IL-8 was
      significantly elevated in citrated blood, but not in heparinized blood, when
      compared to baseline samples that were also incubated for 24 hours. CONCLUSION:
      This study investigates CD11b levels in response to an air stimulus in blood that
      was anticoagulated with citrate or heparin. Exposure to an air stimulus activates
      leucocytes. Activation of CD11b was less when using heparin as an anticoagulant
      compared to citrate. Cytokine activation occurs with air stimulation, but levels
      do not immediately rise, indicating that time is required to generate free
      cytokines.

PMID- 29638200
TI  - Return to Play After Multiligament Knee Injuries in National Football League
      Athletes.
AB  - BACKGROUND:: Return to play (RTP) of National Football League (NFL) athletes
      after isolated anterior cruciate ligament (ACL) tears has been reported. However,
      no studies have reported on RTP of NFL athletes after multiligament knee
      injuries. HYPOTHESES:: NFL athletes with multiligament knee injuries have lower
      RTP rates and longer recoveries than athletes with isolated ACL tears. Second,
      athletes with ACL and medial collateral ligament (MCL) injuries will have higher
      RTP rates and shorter time to RTP than athletes with an ACL tear and
      posterolateral corner involvement. STUDY DESIGN:: Retrospective cohort study.
      LEVEL OF EVIDENCE:: Level 4. METHODS:: Publicly available NFL injury data were
      reviewed for all multiligament knee injuries incurred between 2000 and 2016 with
      RTP information. Athletes were excluded if RTP was limited for reasons unrelated
      to the injury. Extracted data included type of injury, RTP, time to RTP (days),
      number and percentage of games played, and performance. RESULTS:: A total of 50
      NFL athletes with multiligament knee injuries met inclusion and exclusion
      criteria. The overall RTP rate was 64.0%. Athletes with ACL/MCL tears had an RTP
      rate of 70.8%, whereas athletes with ACL and posterior collateral
      ligament/lateral collateral ligament (PCL/LCL) tears had an RTP rate of 55.6% ( P
      = 0.26). Mean time to RTP for all 50 athletes was 388.71 +/- 198.52 days. The
      mean time to RTP for athletes with ACL/MCL injuries was 305.1 +/- 58.9 days,
      compared with 459.2 +/- 245.1 days ( P = 0.004) and 609.3 +/- 183.1 days ( P <
      0.0001) for those with combined ACL and PCL/LCL injuries and frank knee
      dislocations, respectively. Athletes with ACL/MCL injuries were more likely to
      return to prior performance level (43.5%) than those with ACL and PCL/LCL
      injuries (18.5%) ( P < 0.001). CONCLUSION:: The RTP rate for athletes with
      multiligament knee injuries is significantly less than the RTP rate for athletes
      with isolated ACL tears. In addition, athletes with ACL and MCL tears have a
      higher RTP rate, a significantly shorter time to RTP, and a greater likelihood of
      returning to prior performance than athletes with ACL and PCL/LCL tears. CLINICAL
      RELEVANCE:: Multiligament knee injuries significantly affect the ability of a
      football player to return to sport. ACL and MCL tears are associated with better
      RTP prognosis compared with ACL and PCL/LCL tears.

PMID- 29638201
TI  - Hypocalcaemia induced by priming the cardiopulmonary bypass circuit with Plasma
      Lyte 148.

PMID- 29638202
TI  - Comparison of two pediatric cases requiring the use of bivalirudin during
      cardiopulmonary bypass.
AB  - INTRODUCTION: Comparison of two pediatric cases at our institution that utilized
      bivalirudin for anticoagulation on cardiopulmonary bypass (CPB); a bilateral lung
      transplant (BLT) and a ventricular assist device (VAD) implantation. METHODS: The
      same bivalirudin protocol was utilized in both cases with an initial bolus of 1
      mg/kg administered by the anesthesia team, a 50 mg bolus in the pump prime at the
      time of the initial patient bolus and an initial infusion rate of 2.5 mg/kg/h,
      with titration as needed during CPB to maintain kaolin-activated clotting time (K
      ACT) values >400 s. RESULTS: The BLT experienced high K-ACT levels (>720 s) for
      the majority of the case despite decreasing the bivalirudin infusion rate to 0.5
      mg/kg/h. The VAD implantation case required the bivalirudin infusion rate to be
      increased to 5.0 mg/kg/h throughout the case due to low K-ACTs. CONCLUSION: The
      literature strongly supports a specific infusion rate1-7 (2.5 mg/kg/h) for
      bivalirudin anticoagulation during extracorporeal circulation. Clinicians must
      consider the loss of clotting factors and the administration of blood products
      while adjusting the bivalirudin infusion during bypass. We have now elected to
      maintain an infusion rate of >=0.5 mg/kg/h for bivalirudin anticoagulation at our
      center, based on institutional experience, though consideration for a higher
      infusion rate for an added margin of safety should be considered. It is
      imperative to have a well-developed protocol for the management of these
      cardiopulmonary bypass patients and we offer our one-page timeline of events to
      help guide other pediatric centers looking to use bivalirudin anticoagulation.

PMID- 29638204
TI  - Preoperative Serum Insulin-Like Growth Factor 1 Level as a Prognostic Factor in
      Patients Undergoing Hepatic Resection for Hepatocellular Carcinoma.
AB  - In this study, preoperative serum levels of insulin-like growth factor 1 (IGF-1)
      were determined in 216 hepatocellular carcinoma (HCC) patients who underwent
      hepatic resection to investigate a possible contribution of IGF-1 to the
      increased risk for HCC recurrence and mortality. During January 2010 and December
      2013, 216 HCC patients receiving hepatectomy were recruited. The primary endpoint
      was the HCC recurrences within the 3-year follow-up. The secondary endpoint was
      all-cause mortality. The multivariate analyses with Cox regression model were
      applied to explore the clinical significance of IGF-1 serum levels and associated
      parameters on death and recurrence of HCC patients. The IGF-1 levels of included
      patients were determined, with a median value of 75.5 ng/mL (IQR, 40.3-93.0
      ng/mL). The preoperative serum level of IGF-1 was negatively correlated with
      tumor size, Child-Pugh class, or tumor stage (P < 0.001 for all). In multivariate
      models comparing the first, second, and third quartiles with the fourth quartile
      of IGF-1, the levels of IGF-1 in Q1 and Q2 were associated with HCC recurrence,
      with an increased risk of 216% [hazard ratios (HR) = 3.16 (95% CI: 1.79-4.28)]
      and 106% [3.02 (1.36-3.11)]. Similarly, concentrations of IGF-1 in Q1 and Q2 were
      also related to all-cause mortality, with an increased recurrence risk of 238%
      [HR = 3.38 (95% CI: 1.85-4.36)] and 117% [3.02 (1.40-3.21)], respectively. Poor
      prognosis in HCC patients receiving hepatectomy could be indicated by low
      preoperative serum levels of IGF-1, which would be applied as a predictor.

PMID- 29638203
TI  - Acquired infection during neonatal and pediatric extracorporeal membrane
      oxygenation.
AB  - INTRODUCTION: Our objectives are to (1) describe the pathogens, site, timing and
      risk factors for acquired infection during neonatal and pediatric ECMO and (2)
      explore the association between acquired infection and mortality. METHODS:
      Secondary analysis of prospective data collected by the Collaborative Pediatric
      Critical Care Research Network between December 2012 and September 2014. Clinical
      factors associated with acquired infection were assessed with multivariable Cox
      regression. Factors associated with mortality were assessed with logistic
      regression. RESULTS: Of 481 patients, 247 (51.3%) were neonates and 400 (83.2%)
      received venoarterial ECMO. Eighty (16.6%) patients acquired one or more
      infections during ECMO; 60 (12.5%) patients had bacterial, 21 (4.4%) had fungal
      and 11 (2.3%) had viral infections. The site of infection included respiratory
      for 53 (11.0%) patients, bloodstream for 21 (4.4%), urine for 20 (4.2%) and other
      for 7 (1.5%). Candida species were most common. Median time to infection was 5.2
      days (IQR 2.3, 9.6). On multivariable analysis, a greater number of procedures
      for ECMO cannula placement was independently associated with increased risk of
      acquired infection during ECMO (Hazard Ratio 2.13 (95% CI 1.22, 3.72), p<0.01)
      and receiving ECMO in a neonatal ICU compared to a pediatric or cardiac ICU was
      associated with decreased risk (Hazard Ratio pediatric ICU 4.25 (95% CI 2.20,
      8.20), cardiac ICU 2.91 (95% CI 1.48, 5.71), neonatal ICU as reference, p<0.001).
      Acquired infection was not independently associated with mortality. CONCLUSION:
      ECMO procedures and location may contribute to acquired infection risk; however,
      acquired infection did not predict mortality in this study.

PMID- 29638205
TI  - Therapeutic Effect of Duck Interferon-Alpha Against H5N1 Highly Pathogenic Avian
      Influenza Virus Infection in Peking Ducks.
AB  - The antiviral cytokine interferon-alpha (IFN-alpha) plays a critical role in the
      innate immune system. Previous studies have shown that recombinant chicken IFN
      alpha inhibits avian influenza virus (AIV) replication in vivo; however, the
      antiviral effect of recombinant duck IFN-alpha (rDuIFN-alpha) on highly
      pathogenic AIV remains unknown. In this study, the duck IFN-alpha gene was
      cloned, expressed, and purified. The antiviral effects of the resulting rDuIFN
      alpha were further evaluated in vitro and in vivo. Our results showed that rDuIFN
      alpha inhibited the replication of vesicular stomatitis virus (VSV) and AIV in
      duck embryo fibroblasts in vitro, with antiviral activities against VSV and AIV
      of 2.1 * 105 and 4.1 * 105 U/mg, respectively. We next investigated the anti-H5N1
      AIV effect of intramuscular injection of rDuIFN-alpha in vivo. rDuIFN-alpha
      reduced viral titers in the brains, lungs, and spleens of 2-day-old (2D) ducks
      compared with that in the virus-challenged control group, and pretreatment with
      rDuIFN-alpha reduced mortality from 60% to 10% in 2D ducks. Moreover, rDuIFN
      alpha increased the expression of IFN-stimulated genes in the brains and spleens
      of 2D ducks. Our results demonstrate that rDuIFN-alpha blocks VSV and H5N1
      influenza virus infection in vitro and exhibits antiviral effects against H5N1
      influenza virus infection in 2D ducks.

PMID- 29638207
TI  - Interleukin-4 Enhances the Sensitivity of Human Monocytes to Tumor Necrosis
      Factor-Related Apoptosis-Inducing Ligand Through Upregulation of Death Receptor
      4.
AB  - Interleukin (IL)-4 is generally thought to promote tumor cell growth and inhibit
      apoptosis. However, its role in characteristics of monocytic leukemia cells was
      rarely reported. In this study, we assessed the role of IL-4 in tumor necrosis
      factor-related apoptosis-inducing ligand (TRAIL) sensitivity of human monocytes.
      After incubation with IL-4 for 24 h, death receptor 4 (DR4) was significantly
      increased without downregulation of TRAIL decoy receptors and antiapoptotic
      proteins in THP-1 monocytes, and human primary monocytes and U-937 cells also
      exhibited increased TRAIL-induced apoptosis compared with control. Enhancement of
      TRAIL-mediated apoptosis by IL-4 was blocked by anti-DR4-neutralizing antibodies.
      Both upregulation of DR4 and enhancement of TRAIL-mediated apoptosis by IL-4
      could be blocked by inhibitors of Janus kinase (JAK)/signal transducer and
      activator of transcription (STAT), phosphoinositol 3-kinase (PI3K)/Akt, and
      extracellular signal-regulated kinase to varying degrees. Thus, our data
      demonstrated a novel effect on TRAIL sensitivity on monocytes and monocytic
      leukemia cells of IL-4 and suggested that it may be necessary to reconsider the
      impact of current therapies against IL-4, JAK/STAT, and PI3K/Akt pathways with
      regard to TRAIL sensitivity.

PMID- 29638206
TI  - Development of a Validated Interferon Score Using NanoString Technology.
AB  - Chronic elevation of interferon (IFN)-response genes (IRG) in a subset of
      patients with systemic immune-dysregulatory diseases, including the Mendelian
      Type-I IFN-mediated autoinflammatory diseases and some autoimmune diseases
      suggest a causative role of excessive IFN signaling in the disease pathogenesis
      and as target for treatment. We developed a 28-IFN response gene scoring system
      to calculate either a standardized or geomean score by customizing a NanoString
      assay to quantify the expression of putative IRGs. The gene targets were selected
      in patients with the IFN-mediated disease chronic atypical neutrophilic
      dermatosis with lipodystrophy and elevated temperature (CANDLE) and an adult
      patient with chronic hepatitis C who received the first dose of pegylated
      interferon alpha-2a. The putative target genes were validated in patients with
      STING-associated vasculopathy with onset in infancy (SAVI), a monogenic
      autoinflammatory disease caused by gain-of-function mutations in TMEM173 that
      encodes the viral sensor stimulator of IFN genes (STING), and had low expression
      in clinically active patients with the monogenic IL-1-mediated autoinflammatory
      disease, neonatal-onset multisystem inflammatory disease (NOMID) and in healthy
      controls. The score calculation on the NanoString assay is rapid and showed high
      reproducibility and low intra-, and interassay variability. The utility of this
      28-gene IFN score may be explored in the diagnosis of patients with presumed
      interferonopathies and as a biomarker to assess disease activity, long-term
      outcome, and treatment responses.

PMID- 29638208
TI  - Investigation of the Cellular Immune Response to Recombinant Fragments of
      Filamentous Hemagglutinin and Pertactin of Bordetella pertussis in BALB/c Mice.
AB  - Vaccination with whole-cell or acellular (Ac) vaccines has been very effective
      for the control of pertussis. The immune response to Ac vaccines has been
      generally associated with a shift toward the Th2 profile. In the present study,
      overlapping recombinant fragments of filamentous hemagglutinin (FHA) and
      pertactin (PRN) were produced in Escherichia coli. BALB/c mice were immunized
      with recombinant FHA and PRN together with the native pertussis toxin and alum or
      CpG as adjuvant. Immunized mice were subsequently aerosol challenged with
      Bordetella pertussis. Bacterial growth was assessed in bronchoalveolar lavage
      samples and the levels of cytokines were quantitated in supernatants of
      stimulated splenocytes by enzyme-linked immunosorbent assay. Our results
      demonstrated that both PRN and FHA antigens were able to induce IFN-gamma, IL-4,
      and to some extent IL-17 cytokines in challenged mice. The level of IFN-gamma was
      higher in response to CpG formulated antigens. These findings indicate
      immunoprotective efficacy of our recombinant FHA and PRN antigens in mice.

PMID- 29638209
TI  - Identification of Staphylococcus aureus genes involved in the formation of
      structured macrocolonies.
AB  - The human pathogen Staphylococcus aureus causes difficult-to-eradicate biofilm
      associated infections that generally become chronic. Understanding the genetic
      regulation of biofilm formation in S. aureus is central to a precise definition
      of the conditions and genes involved in development of chronic biofilm-associated
      infections. Biofilm-related genes have been detected by comparing mutants using
      the classical submerged biofilm formation assay, in which cells adhere to the
      bottom of a well containing culture medium. We recently developed an alternative
      biofilm formation model for S. aureus, based on macrocolony formation on agar
      plates, comparable to an assay used to study biofilm formation in a few other
      bacterial species. As organism features are the result of environmental
      conditions as well as of genes, we used a genome-wide collection of transposon
      mapped mutants in this macrocolony assay to seek S. aureus developmental genes
      and pathways not identified by the classical biofilm formation assay. We
      identified routes related to glucose and purine metabolism and clarified their
      regulatory link to macrocolony formation. Our study demonstrates that formation
      of microbial communities must be correlated to specific growth conditions, and
      the role of metabolism must be considered in S. aureus biofilm formation and
      thus, in the development of chronic infections.

PMID- 29638210
TI  - Stenotrophomonas lactitubi sp. nov. and Stenotrophomonas indicatrix sp. nov.,
      isolated from surfaces with food contact.
AB  - Five Gram-stain-negative, rod-shaped, none-spore-forming isolates were obtained
      from biofilms on different sites of a milking machine in Germany. Another strain
      with similar morphological characteristics was isolated from dirty dishes. Based
      on phylogenetic analysis of the 16S rRNA and gyrB genes, all isolates were
      assigned to the genus Stenotrophomonas, but were divided into three different
      groups. Chemotaxonomic characterization of the isolates led to the detection of
      iso-C15 : 0 and anteiso-C15 : 0 as the predominant cellular fatty acids, as well
      as small amounts of the hydroxyl fatty acids iso-C11 : 0 3-OH, C12 : 0 3-OH and
      iso-C13 : 0 3-OH. One group could be assigned to the species Stenotrophomonas
      maltophilia, while the genome sequences of two groups displayed average
      nucleotide identity values of less than 94 % between each other and the genome
      sequences of the next related type strains Stenotrophomonas maltophilia ATCC
      13637T and Stenotrophomonas rhizophila DSM 14405T. Further phylogenetic,
      phenotypic and chemotaxonomic analyses enabled the differentiation of these
      strains from these closely related species. They are therefore considered to
      represent two novel species, for which the names Stenotrophomonaslactitubi and
      Stenotrophomonasindicatrix are proposed, with strains M15T (=DSM
      104152T=LMG29943T) and WS40T (=DSM28278T=LMG29942T) as type strains.

PMID- 29638212
TI  - Differences Between Rural and Urban Areas in Mortality Rates for the Leading
      Causes of Infant Death: United States, 2013-2015.
AB  - The leading causes of infant death vary by age at death but were consistent from
      2005 to 2015 (1-6). Previous research shows higher infant mortality rates in
      rural counties compared with urban counties and differences in cause of death for
      individuals aged 1 year and over by urbanization level (4,5,7,8). No research,
      however, has examined if mortality rates from the leading causes of infant death
      differ by urbanization level. This report describes the mortality rates for the
      five leading causes of infant, neonatal, and postneonatal death in the United
      States across rural, small and medium urban, and large urban counties defined by
      maternal residence, as reported on the birth certificate for combined years 2013
      2015.

PMID- 29638211
TI  - Identification of a 'Candidatus Phytoplasma hispanicum'-related strain,
      associated with yellows-type diseases, in smoke-tree sharpshooter (Homalodisca
      liturata Ball).
AB  - The 16SrXIII group from phytoplasma bacteria were identified in salivary glands
      from Homalodisca liturata, which were collected in El Comitan on the Baja
      California peninsula in Mexico. We were able to positively identify 15 16S rRNA
      gene sequences with the corresponding signature sequence of
      'CandidatusPhytoplasma' (CAAGAYBATKATGTKTAGCYGGDCT) and in silico restriction
      fragment length polymorphism (RFLP) profiles (F value estimations) coupled with a
      phylogenetic analysis to confirm their relatedness to 'CandidatusPhytoplasma
      hispanicum', which in turn belongs to the 16SrXIII group. A restriction analysis
      was carried out with AluI and EcoRI to confirm that the five sequences belongs to
      subgroup D. The rest of the sequences did not exhibit any known RFLP profile
      related to a subgroup reported in the 16SrXIII group.

PMID- 29638213
TI  - Prevalence of Depression Among Adults Aged 20 and Over: United States, 2013-2016.
AB  - Major depression is a common and treatable mental disorder characterizedby
      changes in mood, and cognitive and physical symptoms over a 2-weekperiod (1). It
      is associated with high societal costs (2) and greater functionalimpairment than
      many other chronic diseases, including diabetes and arthritis(3). Depression
      rates differ by age, sex, income, and health behaviors (4).This report provides
      the most recent national estimates of depression amongadults. Prevalence of
      depression is based on scores from the Patient HealthQuestionnaire (PHQ-9), a
      symptom-screening questionnaire that allows forcriteria-based diagnoses of
      depressive disorders (5). Estimates for non-HispanicAsian persons are presented
      for the first time.

PMID- 29638214
TI  - Two distinct DNA sequences recognized by transcription factors represent enthalpy
      and entropy optima.
AB  - Most transcription factors (TFs) can bind to a population of sequences closely
      related to a single optimal site. However, some TFs can bind to two distinct
      sequences that represent two local optima in the Gibbs free energy of binding
      (DeltaG). To determine the molecular mechanism behind this effect, we solved the
      structures of human HOXB13 and CDX2 bound to their two optimal DNA sequences,
      CAATAAA and TCGTAAA. Thermodynamic analyses by isothermal titration calorimetry
      revealed that both sites were bound with similar DeltaG. However, the interaction
      with the CAA sequence was driven by change in enthalpy (DeltaH), whereas the TCG
      site was bound with similar affinity due to smaller loss of entropy (DeltaS).
      This thermodynamic mechanism that leads to at least two local optima likely
      affects many macromolecular interactions, as DeltaG depends on two partially
      independent variables DeltaH and DeltaS according to the central equation of
      thermodynamics, DeltaG = DeltaH - TDeltaS.

PMID- 29638215
TI  - The genetic landscape of a physical interaction.
AB  - A key question in human genetics and evolutionary biology is how mutations in
      different genes combine to alter phenotypes. Efforts to systematically map
      genetic interactions have mostly made use of gene deletions. However, most
      genetic variation consists of point mutations of diverse and difficult to predict
      effects. Here, by developing a new sequencing-based protein interaction assay -
      deepPCA - we quantified the effects of >120,000 pairs of point mutations on the
      formation of the AP-1 transcription factor complex between the products of the
      FOS and JUN proto-oncogenes. Genetic interactions are abundant both in cis
      (within one protein) and trans (between the two molecules) and consist of two
      classes - interactions driven by thermodynamics that can be predicted using a
      three-parameter global model, and structural interactions between proximally
      located residues. These results reveal how physical interactions generate
      quantitatively predictable genetic interactions.

PMID- 29638217
TI  - Mechanical and electronic properties of Janus monolayer transition metal
      dichalcogenides.
AB  - The mechanical and electronic properties of Janus monolayer transition metal
      dichalcogenides MXY (M  =  Ti, Zr, Hf, V, Nb, Ta, Cr, Mo, W; X/Y  =  S, Se, Te)
      were investigated using density functional theory. Results show that breaking the
      out-of-plane structural symmetry can be used to tune the electronic and
      mechanical behavior of monolayer transition metal dichalcogenides. The band gaps
      of monolayer WXY and MoXY are in the ranges of 0.16-1.91 and 0.94-1.69 eV,
      respectively. A semiconductor to metallic phase transition occurred in Janus
      monolayer MXY (M  =  Ti, Zr and Hf). The monolayers MXY (M  =  V, Nb, Ta and Cr)
      show metallic characteristics, which show no dependence on the structural
      symmetry breaking. The mechanical properties of MXY depended on the composition.
      Monolayer MXY (M  =  Mo, Ti, Zr, Hf and W) showed brittle characteristic, whereas
      monolayer CrXY and VXY are with ductile characteristic. The in-plane stiffness of
      pristine and Janus monolayer MXY are in the range between 22 and 158 N m-1. The
      tunable electronic and mechanical properties of these 2D materials would advance
      the development of ultra-sensitive detectors, nanogenerators, low-power
      electronics, and energy harvesting and electromechanical systems.

PMID- 29638218
TI  - Phase transformation synthesis of TiO2/CdS heterojunction film with high visible
      light photoelectrochemical activity.
AB  - CdS/TiO2 heterojunction film used as a photoanode has attracted much attention in
      the past few years due to its good visible light photocatalytic activity.
      However, CdS/TiO2 films prepared by conventional methods (successive ionic layer
      adsorption and reaction, chemical bath deposition and electrodeposition) show
      numerous grain boundaries in the CdS layer and an imperfect contact at the
      heterojunction interface. In this study, we designed a phase transformation
      method to fabricate CdS/TiO2 nanorod heterojunction films. The characterization
      results showed that the CdS layer with fewer grain boundaries was conformally
      coated on the TiO2 nanorod surface and the formation mechanism has been explained
      in this manuscript. Moreover, the prepared CdS/TiO2 films show a high
      photocatalytic activity and the photocurrent density is as high as 9.65 mA cm-2
      at 0.80 V versus RHE. It may be attributed to fewer grain boundaries and a
      compact heterojunction contact, which can effectively improve charge separation
      and transportation.

PMID- 29638216
TI  - An efficient and scalable pipeline for epitope tagging in mammalian stem cells
      using Cas9 ribonucleoprotein.
AB  - CRISPR/Cas9 can be used for precise genetic knock-in of epitope tags into
      endogenous genes, simplifying experimental analysis of protein function. However,
      Cas9-assisted epitope tagging in primary mammalian cell cultures is often
      inefficient and reliant on plasmid-based selection strategies. Here, we
      demonstrate improved knock-in efficiencies of diverse tags (V5, 3XFLAG, Myc, HA)
      using co-delivery of Cas9 protein pre-complexed with two-part synthetic modified
      RNAs (annealed crRNA:tracrRNA) and single-stranded oligodeoxynucleotide (ssODN)
      repair templates. Knock-in efficiencies of ~5-30%, were achieved without
      selection in embryonic stem (ES) cells, neural stem (NS) cells, and brain-tumor
      derived stem cells. Biallelic-tagged clonal lines were readily derived and used
      to define Olig2 chromatin-bound interacting partners. Using our novel web-based
      design tool, we established a 96-well format pipeline that enabled V5-tagging of
      60 different transcription factors. This efficient, selection-free and scalable
      epitope tagging pipeline enables systematic surveys of protein expression levels,
      subcellular localization, and interactors across diverse mammalian stem cells.

PMID- 29638219
TI  - Efficient broadband energy detection from the visible to near-infrared using a
      plasmon FET.
AB  - Plasmon based field effect transistors (FETs) can be used to convert energy
      induced by incident optical radiation to electrical energy. Plasmonic FETs can
      efficiently detect incident light and amplify it by coupling to resonant
      plasmonic modes thus improving selectivity and signal to noise ratio. The
      spectral responses can be tailored both through optimization of nanostructure
      geometry as well as constitutive materials. In this paper, we studied various
      plasmonic nanostructures using gold for a wideband spectral response from visible
      to near-infrared. We show, using empirical data and simulation results, that
      detection loss exponentially increases as the volume of metal nanostructure
      increases and also a limited spectral response is possible using gold
      nanostructures in a plasmon to electric conversion device. Finally, we
      demonstrate a plasmon FET that offers a broadband spectral response from visible
      to telecommunication wavelengths.

PMID- 29638220
TI  - Evoked haptic sensations in the hand via non-invasive proximal nerve stimulation.
AB  - OBJECTIVE: Haptic perception of a prosthetic limb or hand is a crucial, but often
      unmet, need which impacts the utility of the prostheses. In this study, we seek
      to evaluate the feasibility of a non-invasive transcutaneous nerve stimulation
      method in generating haptic feedback in a transradial amputee subject as well as
      intact able-bodied subjects. APPROACH: An electrode grid was placed on the skin
      along the medial side of the upper arm beneath the short head of the biceps
      brachii, in proximity to the median and ulnar nerves. Varying stimulation
      patterns were delivered to different electrode pairs, in order to emulate
      different types of sensations (Single Tap, Press-and-Hold, Double Tap) at
      different regions of the hand. Subjects then reported the magnitude of sensation
      by pressing on a force transducer to transform the qualitative haptic perception
      into a quantitative measurement. MAIN RESULTS: Altering current stimulations
      through electrode pairs on the grid resulted in repeatable alterations in the
      percept regions of the hand. Most subjects reported spatial coverage of
      individual fingers or phalanges, which can resemble the whole hand through
      different pairs of stimulation electrodes. The different stimulation patterns
      were also differentiable by all subjects. The amputee subject also reported
      haptic sensations similar to the able-bodied subjects. SIGNIFICANCE: Our findings
      demonstrated the capabilities of our transcutaneous stimulation method. Subjects
      were able to perceive spatially distinct sensations with graded magnitudes that
      emulated tapping and holding sensation in their hands. The elicitation of haptic
      sensations in the phantom hand of an amputee is a significant step in the
      development of our stimulation method, and provides insight into the future
      adaptation and implementation of prostheses with non-invasive sensory feedback to
      the users.

PMID- 29638221
TI  - Self-assembled human osseous cell sheets as living biopapers for the laser
      assisted bioprinting of human endothelial cells.
AB  - A major challenge during the engineering of voluminous bone tissues is to
      maintain cell viability in the central regions of the construct. In vitro
      prevascularization of bone substitutes relying on endothelial cell bioprinting
      has the potential to resolve this issue and to replicate the native bone
      microvasculature. Laser-assisted bioprinting (LAB) commonly uses biological
      layers of hydrogel, called 'biopapers', to support patterns of printed cells and
      constitute the basic units of the construct. The self-assembly approach of tissue
      engineering allows the production of biomimetic cell-derived bone extracellular
      matrix including living cells. We hypothesized that self-assembled osseous sheets
      can serve as living biopapers to support the LAB of human endothelial cells and
      thus guide tubule-like structure formation. Human umbilical vein endothelial
      cells were bioprinted on the surface of the biopapers following a predefined
      pattern of lines. The osseous biopapers showed relevant matrix mineralization and
      pro-angiogenic hallmarks. Our results revealed that formation of tubule-like
      structures was favored when the cellular orientation within the biopaper was
      parallel to the printed lines. Altogether, we validated that human osseous cell
      sheets can be used as biopapers for LAB, allowing the production of human
      prevascularized cell-based osseous constructs that can be relevant for autologous
      bone repair applications.

PMID- 29638222
TI  - Role of cardiac T1 mapping and extracellular volume in the assessment of
      myocardial infarction.
AB  - Although late gadolinium enhancement on cardiac magnetic resonance imaging
      remains the reference standard for scar assessment, it does not provide
      quantitative information about the extent of pathophysiological changes within
      the scar tissue. T1 mapping and extracellular volume (ECV) mapping are steadily
      becoming diagnostic and prognostically useful tests for in vivo myocardial
      histology, influencing clinical decision-making. Quantitative native T1 maps
      (acquired without a contrast agent) represent the longitudinal relaxation time
      within the myocardium and changes with myocardial extracellular water (edema,
      focal, or diffuse fibrosis), fat, iron, and amyloid protein content. Post
      contrast ECV maps estimate the size of the extracellular space and have
      sensitivity in the identification of interstitial disease. Both pre- and post
      contrast T1 mapping are emerging as comprehensive tools for the assessment of
      numerous conditions including ischemic scarring that occurs post myocardial
      infarction (MI). This review outlines the current evidence and potential future
      role of T1 mapping in MI. We conclude by highlighting some of the remaining
      challenges such as quality control, standardization of image acquisition for
      clinical practice, and automated methods for quantifying infarct size, area at
      risk, and myocardial salvage post MI.

PMID- 29638223
TI  - A different approach to multilayer flow modulator implantation in aortic
      aneurysm.

PMID- 29638224
TI  - Milking-like effect in the left anterior descending artery secondary to systolic
      expansion of a post-infarction left ventricular aneurysm.

PMID- 29638225
TI  - A case with a giant interatrial septal lipomatous hypertrophy, and thickened
      epicardial and visceral fat: Different faces of a common metabolic problem?

PMID- 29638226
TI  - Increased microvolt T-wave alternans in children and adolescents with Eisenmenger
      syndrome.
AB  - OBJECTIVE: To determine the values of microvolt T-wave alternans (MTWA) in
      children and adolescents with Eisenmenger syndrome (ES) and controls. METHODS:
      Thirteen were included in the study. After analyzing the 24-h ECG recordings,
      MTWA was considered using three leads (V5, V1, and aVF). Right heart
      catheterization and 6-minute walk test (6-MWD) were applied to the patients and
      pro-brain natriuretic peptide levels were assessed; echocardiographic parameters
      were obtained from both the groups and the results were compared. RESULTS: The
      MTWA value in lead V5 was 81.08+/-10.73 uV in the patient group (63.50+/-18.78 uV
      in the control group), in lead V1 was 75.00+/-16.86 uV (73.94+/-16.77 uV in the
      control group), and in lead aVF was 73.77+/-17.81 uV (72.61+/-16.21 uV in the
      control group). Comparison of MTWA values between patients and controls revealed
      that only lead V5 values were statistically different in the ES group. The 6-MWD
      scores significantly correlated with lead V5. Right atrial volume and right
      ventricular fractional area change were significantly correlated with lead V1.
      The Tei index was significantly correlated with lead aVF. CONCLUSION: The MTWA
      lead V5 value was significantly higher in children with ES than in controls and
      was also correlated with decreased exercise tolerance.

PMID- 29638227
TI  - A toolbox of immunoprecipitation-grade monoclonal antibodies to human
      transcription factors.
AB  - A key component of efforts to address the reproducibility crisis in biomedical
      research is the development of rigorously validated and renewable protein
      affinity reagents. As part of the US National Institutes of Health (NIH) Protein
      Capture Reagents Program (PCRP), we have generated a collection of 1,406 highly
      validated immunoprecipitation- and/or immunoblotting-grade mouse monoclonal
      antibodies (mAbs) to 737 human transcription factors, using an integrated
      production and validation pipeline. We used HuProt human protein microarrays as a
      primary validation tool to identify mAbs with high specificity for their cognate
      targets. We further validated PCRP mAbs by means of multiple experimental
      applications, including immunoprecipitation, immunoblotting, chromatin
      immunoprecipitation followed by sequencing (ChIP-seq), and immunohistochemistry.
      We also conducted a meta-analysis that identified critical variables that
      contribute to the generation of high-quality mAbs. All validation data,
      protocols, and links to PCRP mAb suppliers are available at
      http://proteincapture.org.

PMID- 29638229
TI  - Influence of the 6-month physical activity programs on renal function in obese
      boys.
AB  - BackgroundWe intended to evaluate the effects of physical activity (PA) programs
      on renal function in obese boys.MethodsThirty-nine boys participated in one of
      the following three groups: soccer (SG, n=13), traditional PA (AG, n=13), and
      sedentary control (CG, n=13). SG and AG were involved in 6-month PA programs,
      involving three sessions/week for 60-90 min. Anthropometric measurements, body
      composition, creatinine and cystatin C plasmatic levels, and estimated glomerular
      filtration rate (eGFR) were evaluated.ResultsAt baseline (n=39), age and lean
      mass index (LMI) were positively correlated with creatinine levels. After 6
      months, both intervention groups decreased the BMI z-score and waist
      circumference, while the CG increased the body fat percentage (BFP). LMI
      increased in all the groups. SG presented a small increment in plasma creatinine
      and a decrease in the eGFR values, using the Schwartz formula. Concerning the
      cystatin C levels and eGFR values using Filler (cystatin C-based) or Combined
      Zappitelli (creatinine/cystatin C-based) formulas, no significant changes were
      observed in any group.ConclusionThe combined Zappitelli formula showed no
      significant impact of PA on eGFR in obese boys. Although plasma creatinine is
      significantly influenced by lean body mass, cystatin C is likely to be a more
      accurate marker of renal function in this population.

PMID- 29638228
TI  - Vascular endothelial growth factor accelerates compensatory lung growth by
      increasing the alveolar units.
AB  - BackgroundDeficiency of vascular endothelial growth factor (VEGF) is associated
      with hypoplastic lung diseases, such as congenital diaphragmatic hernia.
      Provision of VEGF has been demonstrated to be beneficial in hyperoxia-induced
      bronchopulmonary dysplasia, and hence could induce lung growth and improve the
      outcome in hypoplastic lung diseases. We aimed to determine the effects of
      exogenous VEGF in a rodent model of compensatory lung growth after left
      pneumonectomy.MethodsEight-to-ten-week-old C57Bl6 male mice underwent left
      pneumonectomy, followed by daily intra-peritoneal injections of saline or VEGF
      (0.5 mg/kg). Lung volume measurement, pulmonary function tests, and morphometric
      analyses were performed on post-operative day (POD) 4 and 10. The pulmonary
      expression of angiogenic factors was analyzed by quantitative polymerase chain
      reaction and western blot.ResultsLung volume on POD 4 was higher in the VEGF
      treated mice (P=0.03). On morphometric analyses, VEGF increased the parenchymal
      volume (P=0.001), alveolar volume (P=0.0003), and alveolar number (P<0.0001) on
      POD 4. The VEGF group displayed higher levels of phosphorylated-VEGFR2/VEGFR2
      (P=0.03) and epidermal growth factor (EGF) messenger RNA (P=0.01).ConclusionVEGF
      accelerated the compensatory lung growth in mice, by increasing the alveolar
      units. These changes may be mediated by VEGFR2 and EGF-dependent mechanisms.

PMID- 29638230
TI  - Coupling free radical catalysis, climate change, and human health.
AB  - We present the chain of mechanisms linking free radical catalytic loss of
      stratospheric ozone, specifically over the central United States in summer, to
      increased climate forcing by CO2 and CH4 from fossil fuel use. This case directly
      engages detailed knowledge, emerging from in situ aircraft observations over the
      polar regions in winter, defining the temperature and water vapor dependence of
      the kinetics of heterogeneous catalytic conversion of inorganic chlorine (HCl and
      ClONO2) to free radical form (ClO). Analysis is placed in the context of
      irreversible changes to specific subsystems of the climate, most notably coupled
      feedbacks that link rapid changes in the Arctic with the discovery that
      convective storms over the central US in summer both suppress temperatures and
      inject water vapor deep into the stratosphere. This places the lower stratosphere
      over the US in summer within the same photochemical catalytic domain as the lower
      stratosphere of the Arctic in winter engaging the risk of amplifying the rate
      limiting step in the ClO dimer catalytic mechanism by some six orders of
      magnitude. This transitions the catalytic loss rate of ozone in lower
      stratosphere over the United States in summer from HOx radical control to ClOx
      radical control, increasing the overall ozone loss rate by some two orders of
      magnitude over that of the unperturbed state. Thus we address, through a
      combination of observations and modeling, the mechanistic foundation defining why
      stratospheric ozone, vulnerable to increased climate forcing, is one of the most
      delicate aspects of habitability on the planet.

PMID- 29638231
TI  - Rapid and label-free identification of single leukemia cells from blood in a high
      density microfluidic trapping array by fluorescence lifetime imaging microscopy.
AB  - The rapid screening and isolation of single leukemia cells from blood has become
      critical for early leukemia detection and tumor heterogeneity interrogation.
      However, due to the size overlap between leukemia cells and the more abundant
      white blood cells (WBCs), the isolation and identification of leukemia cells
      individually from peripheral blood is extremely challenging and often requires
      immunolabeling or cytogenetic assays. Here we present a rapid and label-free
      single leukemia cell identification platform that combines: (1) high-throughput
      size-based separation of hemocytes via a single-cell trapping array, and (2)
      leukemia cell identification through phasor approach and fluorescence lifetime
      imaging microscopy (phasor-FLIM), to quantify changes between free/bound
      nicotinamide adenine dinucleotide (NADH) as an indirect measurement of metabolic
      alteration in living cells. The microfluidic trapping array designed with 1600
      highly-packed addressable single-cell traps can simultaneously filter out red
      blood cells (RBCs) and trap WBCs/leukemia cells, and is compatible with low
      magnification imaging and fast-speed fluorescence screening. The trapped single
      leukemia cells, e.g., THP-1, Jurkat and K562 cells, are distinguished from WBCs
      in the phasor-FLIM lifetime map, as they exhibit significant shift towards
      shorter fluorescence lifetime and a higher ratio of free/bound NADH compared to
      WBCs, because of their glycolysis-dominant metabolism for rapid proliferation.
      Based on a multiparametric scheme comparing the eight parameter-spectra of the
      phasor-FLIM signatures, spiked leukemia cells are quantitatively distinguished
      from normal WBCs with an area-under-the-curve (AUC) value of 1.00. Different
      leukemia cell lines are also quantitatively distinguished from each other with
      AUC values higher than 0.95, demonstrating high sensitivity and specificity for
      single cell analysis. The presented platform is the first to enable high-density
      size-based single-cell trapping simultaneously with RBC filtering and rapid label
      free individual-leukemia-cell screening through non-invasive metabolic imaging.
      Compared to conventional biomolecular diagnostics techniques, phasor-FLIM based
      single-cell screening is label-free, cell-friendly, robust, and has the potential
      to screen blood in clinical volumes through parallelization.

PMID- 29638232
TI  - Assembling silicon quantum dots into wires, networks and rods via metal ion
      bridges.
AB  - Wires and networks of Si quantum dots (QDs) with a length of over 1 MUm and a
      width of ~30 nm are produced by bridging Si QDs with metal ions in solution. It
      is shown that the width of the wires is almost independent of the preparation
      parameters and is always about 30 nm, except for the case when Si QDs larger than
      30 nm are used, while the length of the wires depends strongly on the kinds of
      ions, the amount of ions and the amount of Si QDs in a solution. In addition to
      the microscopic size assemblies, macroscopic size rods of Si QDs with a width of
      ~20 MUm are produced by using Zn2+ ions. The XPS analyses reveal that Si QDs are
      connected to each other via a ZnO layer in the rod. The rods have much higher
      conductivity and photo-response than Si QD solids produced without metal ions.

PMID- 29638233
TI  - Total synthesis of incargranine A.
AB  - Synthetic studies into the origins of the alkaloid incargranine A have resulted
      in the development of a four-step (longest linear sequence) total synthesis. This
      synthesis has been scaled-up to provide gram-scale quantities of material, which
      would alternatively require extraction of several metric-tons of dried-whole
      Chinese Trumpet-Creeper plants (Incarvillea mairei var. grandiflora).

PMID- 29638234
TI  - Polymer platforms for micro- and nanomotor fabrication.
AB  - Artificial, self-propelled micro- and nanomotors are small devices capable of
      autonomous movement, which are a powerful scientific innovation for solving
      various medical and environmental issues. Their design is frequently inspired by
      complex biological structures which are composed of biopolymers and their
      composites. The choice of materials for nano- and micromachines is crucial for
      their shape, mechanism and efficiency of propulsion. In this review, we discuss
      the utilization and fabrication of polymers as soft components of micro- and
      nanomotors.

PMID- 29638235
TI  - [Head injury; the forgotten child of the psychiatry?]

PMID- 29638236
TI  - [The development of a guideline to improve the efficiency and effectiveness of
      FACT board meetings using a Delphi study].
AB  - BACKGROUND: The FACTboard meeting structures the multidisciplinary meetings held
      by FACT teams, held for the 10-20% most care intensive patients. The FACT manual
      only provides a general outline for the FACTboard meeting, leaving out criteria
      specifying the methods to structure meetings. Precisely describing these criteria
      could improve the quality of these meetings. AIM: To develop a more detailed
      guideline on how to structure a FACTboard meeting by means of a Delphi study.
      METHOD: The panel of the Delphi study existed of 22 professions working in
      certified FACT teams and 8 experts in the field of FACT. Panel members
      individually assessed 113 items according to whether the statement should be
      included in the guideline. Statements rated important or essential by >=80% of
      the panel members were included in the guideline. The panel members' commentary
      was used to shape and adjust the statements to clarify why they were regarded as
      important or unimportant. RESULTS: 54 statements were rated essential or
      important by >=80% of the panel members. These statements pertained to the
      organization and structure of the FACTboard meeting and the roles and
      responsibilities of the team members. CONCLUSION: The developed guideline could
      be used by FACT and possibly ACT teams to structure the FACTboard meeting.

PMID- 29638237
TI  - [Efficacy of integrated dual disorder treatment for dual disorder patients: a
      systematic literature review].
AB  - BACKGROUND: Dual diagnosis (substance use disorder combined with a comorbid
      mental illness) is a common problem. One of the methods to treat this is
      integrated dual diagnosis treatment (IDDT). IDDT consists of the simultaneous,
      integrated application of different treatment components. Their efficacy,
      however, has only been studied separately. As a result, the effectiveness of the
      IDDT program as a whole remains unclear. AIM: To evaluate the scientific evidence
      relevant to the effectiveness of IDDT in dual diagnosis patients. METHOD: A
      systematic literature review using MEDLINE, Embase and PsycINFO (Prisma
      guideline). RESULTS: Six studies were found: a randomised controlled study (RCT),
      two non-randomised controlled studies, and three uncontrolled pre-post studies .
      There was a notably large diversity in outcome measures. The results differed
      significantly, including some studies concluding a significant (additional)
      effect, while others concluded that there was no indication of a significant
      effect of IDDT. CONCLUSION: In clinical practice, IDDT is recommended and chosen
      frequently as the treatment for patients with dual diagnosis. However, it is
      remarkable how limited and unthorough the research is pertaining to the effects
      of the full IDDT program on dual diagnosis.

PMID- 29638238
TI  - [How to act in case of a homicidal patient; a literature review and a practice
      guideline].
AB  - BACKGROUND: Death threats are common in the therapist's office. Many therapists
      don't know how to handle these.<br/> AIM: To provide background information and
      tools for the practitioner who receives a homicidal threat from a patient.<br/>
      METHOD: A systematic literature review of the epidemiology, diagnostics, risk
      assessment and treatment of homicidal threats.<br/> RESULTS: During consultation,
      a death threat is not equatable with the announcement of murder. There are far
      more instances where the patient does not follow through with their threat. A
      psychotic disorder, an antisocial personality disorder, alcohol abuse, (bipolar)
      depression, long-existing (severe) domestic violence, possession of a weapon or a
      previous conviction for a death threat are important risk increasing factors. The
      risk assessment evaluates the motives and the proclivity to act. emdr and
      aggression regulation therapy appear to be effective treatments for underlying
      trauma and anger. However, psycho-dynamic aspects and feelings of
      countertransference should also be taken into account during therapy. Three Dutch
      guidelines about professional secrecy are important when making an assessment
      about whether or not one should break the rules of confidentiality.<br/>
      CONCLUSION: Any practitioner who may be faced with a homicidal patient should
      have ready access to the relevant guidelines. Mental health institutions are
      encouraged to actively support this process.

PMID- 29638239
TI  - [The prevention of Korsakoff's syndrome by offering involuntary care?]
AB  - BACKGROUND: The new draft Law on care and coercion focuses on the care of people
      with a psychogeriatric disorder or intellectual disability. Perhaps this law can
      be applied to people suffering from chronic alcoholism, associated with an
      increased risk of Korsakoff's syndrome. AIM: To explore whether the new draft law
      on care and coercion can be applied to people suffering from chronic alcoholism
      who still live at home. METHOD: A description of possibilities of involuntary
      homecare to people suffering from chronic alcoholism based on literature, current
      legislation and two new draft laws. RESULTS: It seems possible to apply the law
      care and coercion to people suffering from chronic alcoholism. CONCLUSION: The
      application of the draft law care and coercion offers the possibility of
      providing involuntary homecare to people suffering from chronic alcoholism,
      enabling the administration of thiamine. This reduces the chances of developing
      Korsakoff's syndrome. Further research is necessary to explore the practical
      possibilities in offering involuntary care.

PMID- 29638240
TI  - [Employment prospects of persons with severe mental illness after an integrated
      mental and psychomotor training in a vocational rehabilitation programme].
AB  - BACKGROUND: There is a lower employment rate among persons with severe mental
      illness.<br/> AIM: In order to increase the employment rate among mentally ill
      patients, azertie, a centre for vocational rehabilitation, has integrated a
      combination of psychomotor and mental training (the I Care concept) into its
      vocational rehabilitation programme. We investigated the results of the azertie
      system via a pilot study<br/> METHOD: Over a period of 10 week period of guided
      training for work, persons with severe mental illness receive three sessions per
      week of mental training and psychomotor training.<br/> RESULTS: 149 clients
      participated in the study. Of these, 70 clients (47%) found employment within the
      year. 50 participants were still receiving training; of these, 10 (6.7%) were
      likely to find employment. At a follow-up after at least one year of employment
      90% of the clients was still at work.<br/> CONCLUSION: The results of this pilot
      study should be interpreted with some caution because we did not use a control
      group. Nevertheless, when we compare the total employment rate (53.7%) with the
      employment rate in the period before the start-up of the I Care programme (10%)
      we can conclude that our programme led to a five-fold increase in the percentage
      of persons in this vulnerable group.

PMID- 29638241
TI  - [Position Statement on religion and spirituality in psychiatry].
AB  - BACKGROUND: In December 2015 the Executive Committee of the World Psychiatric
      Association approved a Position Statement on religion and spirituality in
      psychiatry. This remarkable event remained unnoticed in the Netherlands.<br/>
      AIM: To bring this statement to the attention of the Dutch psychiatry.<br/>
      METHOD: An explanation of the criteria on which the statement is based.<br/>
      RESULTS: Religion and spirituality are a part of daily psychiatric practice,
      scientific research, residency training and continuous medical education.<br/>
      CONCLUSION: The Executive Commitee of the World Psychiatric Association has made
      a major accomplishment in favour of psychiatric practice around the world.

PMID- 29638242
TI  - [An adolescent with conversion deafness].
AB  - A 16-year-old adolescent with progressive hearing loss was diagnosed with a
      conversion disorder after extensive somatic investigations. Psychotherapy led to
      a successful rehabilitation and improved quality of life. In the discussion we
      address the recommendations relating to both diagnostics and approach in good
      clinical practice. The importance of multidisciplinary collaboration is supported
      by research, but remains a challenge in daily practice.

PMID- 29638243
TI  - ?

PMID- 29638244
TI  - ?

PMID- 29638245
TI  - Abstracts of the International Psycho-Oncology Society (IPOS) 10th World Congress
      of Psycho-Oncology, 9-13 June 2008, Madrid, Spain.

PMID- 29638269
TI  - Ajulemic acid: potential treatment for chronic inflammation.
AB  - Ajulemic acid (AJA, CT-3, IP-751, JBT-101, anabasum) is a first-in-class,
      synthetic, orally active, cannabinoid-derived drug that preferentially binds to
      the CB2 receptor and is nonpsychoactive. In preclinical studies, and in Phase 1
      and 2 clinical trials, AJA showed a favorable safety, tolerability, and
      pharmacokinetic profile. It also demonstrated significant efficacy in preclinical
      models of inflammation and fibrosis. It suppresses tissue scarring and stimulates
      endogenous eicosanoids that resolve chronic inflammation and fibrosis without
      causing immunosuppression. AJA is currently being developed for use in 4 separate
      but related indications including systemic sclerosis (SSc), cystic fibrosis,
      dermatomyositis (DM), and systemic lupus erythematosus. Phase 2 clinical trials
      in the first 3 targets demonstrated that it is safe, is a potential treatment for
      these orphan diseases and appears to be a potent inflammation-resolving drug with
      a unique mechanism of action, distinct from the nonsteroidal anti-inflammatory
      drug (NSAID), and will be useful for treating a wide range of chronic
      inflammatory diseases. It may be considered to be a disease-modifying drug unlike
      most NSAIDs that only provide symptomatic relief. AJA is currently being
      evaluated in 24-month open-label extension studies in SSc and in skin-predominant
      DM. A Phase 3 multicenter trial to demonstrate safety and efficacy in SSc has
      recently been initiated.

PMID- 29638270
TI  - Equipping an urban hospital police and security team with Narcan.
AB  - Narcan, the nasal-spray form of naloxone, has been approved by the FDA as an easy
      to-use version of a drug for saving lives of people who have overdosed on opioids
      -heroin or prescription painkillers. Communities across the US have been
      equipping first responders and police with the spray. Now, as the increase in
      overdose deaths has spread to hospitals, those facilities will have to decide
      whether their police/security officers should be equipped with. naloxone and
      trained in its use. In this article, the authors relate their health system's
      decision, how it was reached, and how it has been implemented.

PMID- 29638271
TI  - Are you ready for Medical Cannabis?
AB  - In states which permit the use of medical cannabis, a number of problems have
      arisen for hospitals when they admit patients which have such permission, the
      author reports. In this article he presents the many issues that medical cannabis
      will create and stresses that now is the time to prepare the strategy to address
      these issues.

PMID- 29638272
TI  - If we're not looking, the children will remain missing.
AB  - In every community human trafficking has become more apparent to healthcare
      providers. Children who are missing are at risk for ex- ploitation and harm. In
      response to the identification of missing youths in the emergency room setting, a
      guideline has been developed as a tool for healthcare providers to identify and
      appropriately respond to a child who is reported missing and at risk for harm. In
      this article, the author provides guidance for security and other ER personnel on
      how to identify such children.

PMID- 29638273
TI  - Security's role in supporting a hospital's Early Intervention Program for inner
      city children.
AB  - The availability of an Early Intervention Program for at-risk children in New
      Jersey's city with the highest crime rate and poverty level has been enhanced
      several fold by a volunteer escort service provided by security officers of
      hospitals which serve the community. In this article, the lead author and
      contributors explain in detail how an Early Intervention Program works and the
      key contribution to its success by hospital security escorts.

PMID- 29638274
TI  - The case for body cameras in a healthcare environment.
AB  - The author, an experienced investigator and trainer, makes the case in this
      article for the use of body cameras by healthcare security and non-security
      personnel to confirm that they acted within policy, law, and regulatory
      guidelines during an incident. The many benefits of such cameras in enhancing
      training of healthcare personnel are also described.

PMID- 29638275
TI  - Disaster preparedness and response in healthcare: a review of the basics.
AB  - In this article, the author reviews the four elements of disaster preparation
      that healthcare facilities should have in place to respond effectively in an
      emergency situation.

PMID- 29638276
TI  - The role of security in the prevention, detection and response to drug diversion
      by healthcare personnel.
AB  - Drug diversion by healthcare personnel poses substantial and growing risks to
      patients, staff, healthcare institutions and the community, the author reports.
      It is essential that clinical, pharmacy, and security personnel work together on
      diversion-related issues to reduce those risks, she says. In this article she
      spells out the critical roles of security personnel in the investigation of
      suspected diversion and the response to confirmed diversion.

PMID- 29638277
TI  - Do it yourself biology--committed hobbyists or dangers to the public safety?
AB  - In this article some of the concepts that undergird the Do It Yourself Bio or the
      "DIY Bio" movement will be explored; the challenges of citizen science will be
      considered; some of the public policy concerns linked to Do it Yourself Bio will
      be sketched; and some actionable recommendations made, especially for healthcare
      institutions.

PMID- 29638278
TI  - The battle against violence in U.S. hospitals: an analysis of the recent I IAHSS
      Foundation's healthcare crime surveys.
AB  - In this article, the author analyzes the possible reasons for the reported drop
      in hospital violence in the 2016IAHSS Crime Survey compared to previous surveys.
      He also reviews the one statistic that has remained constant in all the recent
      crime surveys and recommends an approach in violence prevention programs that may
      prove successful in reducing workplace violence and staff injuries.

PMID- 29638279
TI  - All tied up: the fine art of balancing regulatory restraint compliance and
      excellent patient care.
AB  - This article presents examples of different resources that can be implemented to
      help manage a patient in crisis. It discusses challenges and solutions in regard
      to the ED boarding of behavioral health patients and reviews various restraint
      types and definitions (violent, non-violent, forensic). It stresses the
      importance of teamwork between security police and clinicians.

PMID- 29638280
TI  - Evaluating the need for firearms in healthcare security.
AB  - This article is a condensed version of a document/position paper written by the
      authors for ODS Security Solutions on "Defensive Weapons and Equipment in the
      Healthcare Environment." For the complete paper, which also includes a review of
      alternative weapons and equipment and other equipment carried by security
      officers go to: http://ods-security.com/wp-content/uploads/2016/05/Defensive
      Weapons _Digital
      2.pdf?utm_source=Defensive+Weapons&utm_campaign=spring+sentinel&utm_medium=email.

PMID- 29638281
TI  - The benefits of Taser CEWs in a healthcare setting.
AB  - In this article, the authors maintain that if properly used by trained security
      officers Taiser CEWs result in significant reductions in injuries and reduction
      in costs by type of injury. HSS's security officers have carried Taser CEW's in
      hospitals for more than 10 years in 40 facilities across the country producing no
      negative CMS finding or excessive use of force claims, they report.

PMID- 29638283
TI  - Increasing your HCAHPS scores with Extreme Customer Service.
AB  - Providing great customer service is extremely critical in the healthcare setting,
      especially when it comes to HCAHBPS (Hospital Consumer Assessment of Health care
      Providers and Systems) scores, the author says. While there are several service
      training programs within healthcare, they often require six to eight minutes of
      interaction with patients or guests. This works well for clinical staff, he says,
      but when it comes to non-clinical staff, including security officers, many times
      they only have fifteen or thirty seconds to create positive patient or guest
      experience. In this article he describes Extreme Customer Service

PMID- 29638282
TI  - A new approach to handling incoming verifications.
AB  - Outside requests for data on current or former employees are handled in different
      ways by healthcare organizations and present considerable liability risks if a
      corporate policy for handling such risks is not in place. In this article, the
      authors present a strategy for responsible handling of sensitive information.

PMID- 29638285
TI  - How an acute care hospital reduced workplace violence injuries by more than 50
      percent in a single year.
AB  - The formation of well trained, organized, and supervised clinical staff working
      in collaboration with security officers, has resulted in a reduction of work
      place violence injuries to staff, according to the authors. In addition, the rate
      of restraint deployment for disruptive patients has also been reduced.

PMID- 29638284
TI  - Why security fails.
AB  - When a hospital suffers a serious loss or act of violence, the blame frequently
      centers on the facility's Security Department, but, as the author, a longtime
      security consultant, points out, there's plenty of blame to go around--including
      Administration at all levels, and employees, both clinical and non clinical. In
      this article, he presents the many reasons why security can fail and what should
      be done to prevent such failure.

PMID- 29638286
TI  - Reducing the risk of patient-generated violence in healthcare: a case study.
AB  - This case study excerpted from a white paper by HSS, Denver, CO, demonstrates how
      an integrated approach to addressing the problem of violence in healthcare
      through staff training and adopting environmental controls can significantly
      improve employee safety, business measures and practices, and allow staff to
      focus on providing high quality patient-focused care. For the complete white
      paper, go to the following link: http://hss-us.com/wp
      content/uploads/2014/11/EDSafe-TEAM-Methodist-White-Paper-2014. pdf.

PMID- 29638287
TI  - Modern strategy for operational excellence: building agile and adaptive
      organizations.
AB  - Healthcare security leaders who serve in an industry built on traditional and
      static protection and response protocols must become more agile and adaptive in
      planning and responding to evolving threat and risk profiles, the author states.
      In this article, he tells how to use operational excellence to continuously
      improve performance.

PMID- 29638288
TI  - Community model of healthy aging framed in resilience and generativity
AB  - The Research Unit in Gerontology at the Facultad de Estudios Superiores (FES)
      Zaragoza, from the Universidad Nacional Autonoma de Mexico (UNAM), has developed
      a comprehensive model aimed at the promotion of healthy aging within the context
      of community development. The model is centered on the implementation of
      intensive educational programs addressed towards groups of older persons in what
      is known as "Gerontological Nuclei". Although it is true that there are
      satisfactory results, one limitation of the model is the difficulty of its
      implementation without supervision and university support. For this reason, two
      components have been included: resilience and generativity, which together could
      positively impact the model by strengthening contextual and personal components
      that are linked to healthy behavior. The approach of generativity and resilience
      are basic elements for the strengthening of human capacities during aging, since
      they can favor the autonomy, independence and decision-making capacity of people
      in the personal and community spheres. The article presents a model of healthy
      aging with possibilities of application at community level.

PMID- 29638289
TI  - Progress on Fault Mechanisms for Gear Transmissions in Coal Cutting Machines:
      From Macro to Nano Models.
AB  - Numerical modeling has been recognized as the dispensable tools for mechanical
      fault mechanism analysis. Techniques, ranging from macro to nano levels, include
      the finite element modeling boundary element modeling, modular dynamic modeling,
      nano dynamic modeling and so forth. This work firstly reviewed the progress on
      the fault mechanism analysis for gear transmissions from the tribological and
      dynamic aspects. Literature review indicates that the tribological and dynamic
      properties were separately investigated to explore the fault mechanism in gear
      transmissions. However, very limited work has been done to address the links
      between the tribological and dynamic properties and scarce researches have been
      done for coal cutting machines. For this reason, the tribo-dynamic coupled model
      was introduced to bridge the gap between the tribological and dynamic models in
      fault mechanism analysis for gear transmissions in coal cutting machines. The
      modular dynamic modeling and nano dynamic modeling techniques are expected to
      establish the links between the tribological and dynamic models. Possible future
      research directions using the tribo dynamic coupled model were summarized to
      provide potential references for researchers in the field.

PMID- 29638291
TI  - The Preparation of an Optical Hydrogen Peroxide Sensor Using Polydopamine as a
      Sensing Medium.
AB  - Polydopamine (PDA) is well known as an excellent coating material. It has various
      novel properties such as good biocompatibility, biodegradability, nontoxicity,
      easiness of deposit on all types of substrates, and strong stability as a primary
      natural pigment. In this research, in situ preparation of fluorescent PDA was
      performed by the addition of hydrogen peroxide (H2O2) to dopamine (DA) in the
      presence of Cu2+. DA does not show any fluorescence while the in situ self
      initiated PDA has a strong fluorescence at 480 nm with excitation wavelength
      ranged from 330 nm to 420 nm due to the oxidation of DA by H2O2. A novel H2O2
      sensor was fabricated using PDA as a fluorescence sensing medium. High
      sensitivity and linear response were achieved with a detection limit of 0.7 MUM.
      The sensing medium is not toxic and allows biodegradation, which indicates high
      potential for in vivo application.

PMID- 29638290
TI  - Phenomena of Nano- and Micro-Pore Formation on Ti-(10~50)Ta Alloys by Plasma
      Electrolytic Oxidation for Dental Implants.
AB  - In this study, the phenomena of nano and micro-pore formation on Ti-(10~50)Ta
      alloys by plasma electrolytic oxidation for dental implants was investigated
      using various experimental techniques. The Ti-xTa alloys having Ta contents of
      10, 30, and 50 wt.% were prepared using arc-melting vacuum furnace. Micro-pore
      formation was performed using a potentiostat in 1 M H3PO4 electrolyte by using a
      potentiostat at various applied voltage (180 V, 210 V, and 240 V). The
      microstructure of Ti-xTa alloys changed from alpha' phase to beta + alpha" phase
      with Ta content increased. The applied potential increased, the numbers of micro
      pore per unit area decreased, whereas the area ratio of occupied by micro-pores
      increased. The Ta contents increased, the numbers of micro-pore per unit area
      decreased, whereas the area ratio of occupied by micro-pores increased at 210 V
      and 240 V. The thickness of oxide layer and micro-pore size can be controlled by
      applied potential.

PMID- 29638292
TI  - Sol-Gel Synthesis of Manganese Doped Titanium Oxide Nanoparticles for
      Electrochemical Sensing of Hydroquinone.
AB  - Here we report development of a hydroquinone (HQ) electrochemical sensor using
      nanosized manganese doped titanium oxide as a composite material. The
      nanomaterial was synthesized with sol gel method using calculated amount of Mn
      and Ti atoms resulting into a composite metal oxide. Morphological observations
      indicated a uniform particle size and shape distribution with almost spherical
      shape and size of about 20-30 nm. While structural analysis indicated formation
      of mixed phase of TiO2 and MnO forming MnTiO3. The synthesized nanomaterial was
      used as a matrix for fabrication of hydroquinone electrochemical sensor and
      tested over a wide range from 2 mM to 10 mM. The developed electrochemical sensor
      exhibited sensitivity of 2.96 MUA mM-1 (23.55 MUA mM-1 cm-2) with a detection
      limit of 7.5 MUM, which is rarely reported for such composite nanomaterial.

PMID- 29638306
TI  - House Infection in Cholera and Cancer.

PMID- 29638307
TI  - A Case of Extensive Resection of Small Intestine, with a Clinical Study of
      Recorded Cases.

PMID- 29638293
TI  - Microbial Precipitation of Cr(III)-Hydroxide and Se(0) Nanoparticles During
      Anoxic Bioreduction of Cr(VI)- and Se(VI)-Contaminated Water.
AB  - This study examined the microbial precipitations of Cr(III)-hydroxide and Se(0)
      nanoparticles during anoxic bioreductions of Cr(VI) and Se(VI) using metal
      reducing bacteria enriched from groundwater. Metal-reducing bacteria enriched
      from groundwater at the Korea Atomic Energy Research Institute (KAERI)
      Underground Research Tunnel (KURT), Daejeon, S. Korea were used. Metal reduction
      and precipitation experiments with the metal-reducing bacteria were conducted
      using Cr(VI)- and Se(VI)-contaminated water and glucose as a carbon source under
      an anaerobic environment at room temperature. XRD, SEM-EDX, and TEM-EDX analyses
      were used to characterize the mineralogy, crystal structure, chemistry, shape,
      and size distribution of the precipitates. The metal-reducing bacteria reduced
      Cr(VI) of potassium chromate (K2CrO4) to Cr(III) of chromium hydroxide [Cr(OH)3],
      and Se(VI) of sodium selenate (Na2SeO4) to selenium Se(0), with changes of color
      and turbidity. XRD, SEM-EDX, and TEM-EDX analyses revealed that the chromium
      hydroxide [Cr(OH)3] was formed extracellularly with nanoparticles of 20-30 nm in
      size, and elemental selenium Se(0) nanoparticles had a sphere shape of 50-250 nm
      in size. These results show that metal-reducing bacteria in groundwater can aid
      or accelerate precipitation of heavy metals such as Cr(VI) and Se(VI) via
      bioreduction processes under anoxic environments. These results may also be
      useful for the recovery of Cr and Se nanoparticles in natural environments.

PMID- 29638308
TI  - Plastic Repair of the Face and Limbs.

PMID- 29638309
TI  - Clinical Meeting.

PMID- 29638310
TI  - The Occupation-Cure in Neurasthenia.

PMID- 29638311
TI  - The Treatment of Diabetes with Insulin.

PMID- 29638312
TI  - The Benefits of Organisation in the Treatment of Lupus.

PMID- 29638313
TI  - Artificial Pneumothorax in the Treatment of Pulmonary Tuberculosis.

PMID- 29638314
TI  - Discussion on Focal Infection in Relation to Disease.

PMID- 29638315
TI  - Influenza, Cerebro-Spinal Meningitis, and Epidemic Encephalitis: Some Etiological
      Considerations.

PMID- 29638317
TI  - The Nutritional Treatment of Tuberculosis.

PMID- 29638316
TI  - Hydrocephalus.

PMID- 29638319
TI  - Principles of Bone Graft Surgery.

PMID- 29638318
TI  - Exhibition of Patients.

PMID- 29638320
TI  - Case of Intestinal Obstruction from Carcinoma of Descending Colon in a Man Aged
      22 Suffering from Achondroplasia-Formation of Artificial Anus; Subsequent
      Resection of Affected Bowel, and Reunion of the Bowel-Recovery.

PMID- 29638321
TI  - Valedictory Address.

PMID- 29638322
TI  - Medicine.

PMID- 29638323
TI  - On Addison's Disease, with Two Cases; and Also a Case Which Presented the
      Symptoms of Disease of the Suprarenal Capsules.

PMID- 29638324
TI  - Pathology and Bacteriology.

PMID- 29638325
TI  - Therapeutics.

PMID- 29638326
TI  - The Decrease in the Birth-Rate.

PMID- 29638328
TI  - Obstetrics and Gynaecology.

PMID- 29638327
TI  - Surgery.

PMID- 29638330
TI  - Diseases of the Eye.

PMID- 29638331
TI  - Physiology.

PMID- 29638329
TI  - The Therapeutic Value of Relaxing Climates.

PMID- 29638333
TI  - Reports of the Medical Societies.

PMID- 29638332
TI  - A Case of Anaemia and One of Acute Lymphocythaemia, with Special Reference to
      Conditions of Aplasia of the Haemopoietic Tissues in Leukaemia.

PMID- 29638334
TI  - Case of Typhus Fever, Followed by Right Hemiplegia and Loss of Intellectual
      Language, Both Articulate and Written (Amnesic Aphasia).

PMID- 29638335
TI  - Nature of Eczema and Psoriasis.

PMID- 29638336
TI  - Case of Molluscum.

PMID- 29638337
TI  - Erratum: Public Health Practice in the Tropics.
AB  - [This corrects the article on p. 492 in vol. 38.].

PMID- 29638338
TI  - Medical News.

PMID- 29638339
TI  - Medical News.

PMID- 29638341
TI  - Medical News.

PMID- 29638340
TI  - Medical News.

PMID- 29638342
TI  - Medical News.

PMID- 29638343
TI  - Medical News.

PMID- 29638344
TI  - Report on Ophthalmology.

PMID- 29638345
TI  - Observations on the Therapeutic Value of Chloral.

PMID- 29638346
TI  - On Feigned Diseases, Their Detection and Management.

PMID- 29638347
TI  - Case of Puerperal Scarlet Fever.

PMID- 29638348
TI  - Notes from Practice, New and Old.

PMID- 29638350
TI  - On Atmospheric Influences.

PMID- 29638349
TI  - A Few Words on Vaccination and Revaccination.

PMID- 29638351
TI  - On Dementia.

PMID- 29638353
TI  - Physiological Notes.

PMID- 29638352
TI  - Clinical Lectures on Diseases of the Heart.

PMID- 29638354
TI  - The Restoration of the Perineum.

PMID- 29638355
TI  - Case of Sudden Death from an Aneurism of the Arch Bursting into the Pericardium.

PMID- 29638356
TI  - Notes of a Case of Scleriasis.

PMID- 29638357
TI  - The Normal Products of Hepatic Action.

PMID- 29638359
TI  - Meetings of Societies.

PMID- 29638358
TI  - On the Mode of Introducing the Midwifery Forceps; with Note on Their
      Modification.

PMID- 29638360
TI  - On the Use of Carbolic Acid to Prevent Pitting after Smallpox.

PMID- 29638361
TI  - Periscope.

PMID- 29638362
TI  - Intestinal Obstruction from a Knot on the Lower Part of the Ileum.

PMID- 29638363
TI  - On Some Cases Illustrating the Results of Excision of the Wrist for Caries, the
      Treatment of Deformity from Contracted Cicatrix, and Antiseptic Dressing under
      Circumstances of Difficulty, Including Amputation at the Hip-Joint.

PMID- 29638364
TI  - Notes of a Case of Ovarian Disease-Ascites-Anasarca-Solid Tumour in Both Ovaries.

PMID- 29638365
TI  - On Mining Exhalations.

PMID- 29638366
TI  - Medical News.

PMID- 29638369
TI  - Chloral in Obstetrics.

PMID- 29638368
TI  - Medical News.

PMID- 29638367
TI  - On the Principles Which Have Determined the Classifications of Mental Diseases.

PMID- 29638370
TI  - Record of the Cases of Tumours of the Breast Admitted into the Clinical Wards of
      the Edinburgh Royal Infirmary from 1833 to 1869.

PMID- 29638371
TI  - Polypus of the Uterus.

PMID- 29638372
TI  - Meetings of Societies.

PMID- 29638373
TI  - A Graduation Address.

PMID- 29638374
TI  - Note on the History of Ovariotomy.

PMID- 29638377
TI  - The Therapeutic Actions and Uses of Turpentine.

PMID- 29638375
TI  - Carbolic Acid, from a Septic Point of View.

PMID- 29638376
TI  - Criminal Lunacy in Scotland for Quarter of a Century, Viz., from 1846 to 1870,
      Both Inclusive.

PMID- 29638379
TI  - Nitro-Muriatic Acid in Urticaria.

PMID- 29638378
TI  - On a Case of Trance.

PMID- 29638380
TI  - Medical News.

PMID- 29638381
TI  - Case of Paralysis and Sudden Death in the Pregnant State.

PMID- 29638382
TI  - Letter from Creuznach.

PMID- 29638383
TI  - Diphtheria of the Throat.

PMID- 29638385
TI  - Navy Medical Department.

PMID- 29638384
TI  - On Feigned Diseases, Their Detection and Management.

PMID- 29638386
TI  - Medical News.

PMID- 29638387
TI  - Ergotine as a Haemostatic.

PMID- 29638388
TI  - Information Regarding Medical Education and Examinations.

PMID- 29638389
TI  - A New Test for Hysteria.

PMID- 29638390
TI  - On Artificial Tuberculosis, and Its Relation to Cellular Pathology and the Growth
      of Tumours.

PMID- 29638391
TI  - Hydrate of Chloral in Insanity.

PMID- 29638393
TI  - Suggestions as to the Use of Calabar Bean in Cholera Asiatica.

PMID- 29638392
TI  - Remarks on Medical Study.

PMID- 29638394
TI  - Perforation of the Uterine Walls by a Sound.

PMID- 29638395
TI  - Army Medical Department.

PMID- 29638396
TI  - Army Medical School.

PMID- 29638397
TI  - Indian Medical Service.

PMID- 29638398
TI  - General Neuralgia.

PMID- 29638400
TI  - Chloride of Sodium.

PMID- 29638399
TI  - Case of Deformity of the Pelvis, in Which Caesarean Section Was Performed; with
      Remarks.

PMID- 29638402
TI  - List of Hospitals, Dispensaries, Etc., in Connexion with the Medical Schools of
      Scotland.

PMID- 29638401
TI  - Sympathetic Insanity Illustrated-The Influence of the Body on the Mind, and the
      Mind on the Body.

PMID- 29638403
TI  - Notes on Cases of Yellow Fever in St Kitts, W.I., during 1868, '69, '70.

PMID- 29638404
TI  - Digitalis, Its Use and Action.

PMID- 29638406
TI  - How to Keep a Horse Quiet.

PMID- 29638405
TI  - A Few Cursory Remarks upon the Treatment of Some of the Specific and Septic
      Fevers.

PMID- 29638407
TI  - Cases of Amputation of the Penis; with Remarks.

PMID- 29638410
TI  - Treatment of Hip-Joint Disease.

PMID- 29638408
TI  - The Normal Products of Hepatic Action.

PMID- 29638409
TI  - Case of Ovario-Mania.

PMID- 29638412
TI  - Medical News.

PMID- 29638411
TI  - Meetings of Societies.

PMID- 29638413
TI  - Dangers of Chromic Acid.

PMID- 29638414
TI  - Ovaritis.

PMID- 29638415
TI  - Medical News.

PMID- 29638417
TI  - Chlorine Water in the Treatment of Diphtheria.

PMID- 29638416
TI  - Penetrating Wounds of the Chest.

PMID- 29638418
TI  - Sympathetic Insanity Illustrated-The Influence of the Body on the Mind, and the
      Mind on the Body.

PMID- 29638420
TI  - A Cause of Heart Disease in the Army.

PMID- 29638419
TI  - On Feigned Diseases, Their Detection and Management.

PMID- 29638421
TI  - Case of Haematemesis Treated by the Hypodermic Injection of Ergotine.

PMID- 29638422
TI  - On the Local Effects of Crude Paraffin.

PMID- 29638423
TI  - Meetings of Societies.

PMID- 29638424
TI  - On the Treatment of Diabetes by Lactic Acid (Cantani's Method).

PMID- 29638425
TI  - Case of Popliteal Aneurism.

PMID- 29638426
TI  - Introductory Address, Delivered at the Opening of the Edinburgh School of
      Medicine, on the 1st of November 1871.

PMID- 29638427
TI  - Dislocation of the Scaphoid.

PMID- 29638429
TI  - Case of Strangulated Hernia.

PMID- 29638430
TI  - Letters from Vienna.-No. I.

PMID- 29638428
TI  - Injury to the Cervical Vertebrae.

PMID- 29638431
TI  - The Melanomata. A Histological, Clinical, and Critical Study.: Bibliography.

PMID- 29638432
TI  - The Melanomata. A Histological, Clinical, and Critical Study.: Preface.

PMID- 29638433
TI  - The Melanomata. A Histological, Clinical, and Critical Study.: IV. Critical
      Discussion.

PMID- 29638434
TI  - The Melanomata. A Histological, Clinical, and Critical Study.: Plates and
      Descriptions of Plates.

PMID- 29638435
TI  - The Melanomata. A Histological, Clinical, and Critical Study.: II. Histological
      Study.

PMID- 29638436
TI  - The Melanomata. A Histological, Clinical, and Critical Study.: I. Introduction.

PMID- 29638437
TI  - The Melanomata. A Histological, Clinical, and Critical Study.: III. Clinical
      Study.

PMID- 29638439
TI  - House Infection in Cholera and Cancer.

PMID- 29638438
TI  - The Melanomata. A Histological, Clinical, and Critical Study.: V. Conclusion.

PMID- 29638442
TI  - Clinical Meeting.

PMID- 29638440
TI  - A Case of Extensive Resection of Small Intestine, with a Clinical Study of
      Recorded Cases.

PMID- 29638441
TI  - Plastic Repair of the Face and Limbs.

PMID- 29638443
TI  - The Occupation-Cure in Neurasthenia.

PMID- 29638444
TI  - The Treatment of Diabetes with Insulin.

PMID- 29638445
TI  - The Benefits of Organisation in the Treatment of Lupus.

PMID- 29638446
TI  - Artificial Pneumothorax in the Treatment of Pulmonary Tuberculosis.

PMID- 29638447
TI  - Discussion on Focal Infection in Relation to Disease.

PMID- 29638448
TI  - Influenza, Cerebro-Spinal Meningitis, and Epidemic Encephalitis: Some Etiological
      Considerations.

PMID- 29638449
TI  - Hydrocephalus.

PMID- 29638450
TI  - The Nutritional Treatment of Tuberculosis.

PMID- 29638451
TI  - Exhibition of Patients.

PMID- 29638452
TI  - Principles of Bone Graft Surgery.

PMID- 29638453
TI  - On the Construction of Hospitals.

PMID- 29638454
TI  - Meetings of Societies.

PMID- 29638455
TI  - Observations on Amputation at the Hip-Joint.

PMID- 29638456
TI  - Medical News.

PMID- 29638458
TI  - General Council of Medical Education and Registration. Session 1870.

PMID- 29638457
TI  - Case of Popliteal Aneurism Treated by Compression.

PMID- 29638459
TI  - An Aid to Parturition, and to the Treatment of Displacements of the Uterus, by a
      New Mechanical Appliance.

PMID- 29638461
TI  - Surgery.

PMID- 29638460
TI  - Remarks on Pelvic Peritonitis and Pelvic Cellulitis, with Illustrative Cases.

PMID- 29638463
TI  - Medical News.

PMID- 29638464
TI  - Removal of a Large Uterine Fibrous Polypus.

PMID- 29638462
TI  - Case of Death from a Strangulated Ovarian Tumour.

PMID- 29638465
TI  - On Unilateral Convulsions, Localization, Etc.

PMID- 29638466
TI  - Surgery.

PMID- 29638467
TI  - Sanitary State of Hong-Kong.

PMID- 29638468
TI  - Meetings of Societies.

PMID- 29638470
TI  - Report on Ophthalmology.

PMID- 29638469
TI  - The Medical Council and Its Critics: A Re-Vindication.

PMID- 29638471
TI  - Contribution to Vital Statistics.

PMID- 29638472
TI  - Our Existing System of Hospitalism and Its Effects.

PMID- 29638473
TI  - Four Cases of Spinal Myosis; with Remarks on the Action of Light on the Pupil.

PMID- 29638474
TI  - On the Use of Petroleum or Earth-Oil as an Antiseptic in the Treatment of
      Surgical Diseases.

PMID- 29638475
TI  - Diseases of Women and Children.

PMID- 29638476
TI  - Clinical Medicine.

PMID- 29638477
TI  - Note on the Sudden Change of Temperature in the Last Week of August 1869.

PMID- 29638478
TI  - University of Edinburgh.

PMID- 29638480
TI  - On the Combined External and Internal Method of Version, with Cases.

PMID- 29638479
TI  - Meetings of Societies.

PMID- 29638481
TI  - The Mortality of Childbed.

PMID- 29638483
TI  - Medical News.

PMID- 29638482
TI  - Surgery.

PMID- 29638484
TI  - A Case of Heart Disease (Cardiac Thrombosis).

PMID- 29638486
TI  - Royal College of Surgeons, Edinburgh.

PMID- 29638485
TI  - The English Doctor in Southern Manchooria.

PMID- 29638487
TI  - Medicine.

PMID- 29638488
TI  - Dr Wood's Correction in Regard to Clinical Examinations of London Apothecaries'
      Company.

PMID- 29638489
TI  - The Indian Medical Service.

PMID- 29638491
TI  - Recent Researches on Tuberculosis.

PMID- 29638490
TI  - On the Action of the Cobra Poison.

PMID- 29638493
TI  - Medical News.

PMID- 29638492
TI  - Medical News.

PMID- 29638494
TI  - Continued Observations on Haemoptysis.

PMID- 29638495
TI  - Meetings of Societies.

PMID- 29638497
TI  - University of Edinburgh.

PMID- 29638496
TI  - Case of Pelvic Haematocele.

PMID- 29638499
TI  - Medicine.

PMID- 29638498
TI  - Amputation of the Scapula, along with Two-Thirds of the Clavicle and the Remains
      of the Arm.

PMID- 29638500
TI  - General Council of Medical Education and Registration.

PMID- 29638501
TI  - The Climate of Madeira.

PMID- 29638502
TI  - Medical News.

PMID- 29638505
TI  - Erratum: Obstetrical Society's Proceedings.
AB  - [This corrects the article on p. 170 in vol. 15.].

PMID- 29638503
TI  - Surgery.

PMID- 29638504
TI  - A Contribution to the Statistics of the Operation for Strangulated Femoral
      Hernia, Being a Record of Fourteen Cases.

PMID- 29638507
TI  - Medicine.

PMID- 29638506
TI  - Graduation in Medicine at the University of Edinburgh.

PMID- 29638508
TI  - On the Therapeutical Value of the Sulphites.

PMID- 29638510
TI  - Address to Dr Joseph Bell.

PMID- 29638509
TI  - Address to the Edinburgh Medical Graduates.

PMID- 29638511
TI  - Surgery.

PMID- 29638512
TI  - Medical News.

PMID- 29638514
TI  - Medical News.

PMID- 29638513
TI  - On the Action of the Cobra Poison.

PMID- 29638515
TI  - Continued Observations on Haemoptysis.

PMID- 29638516
TI  - Successful Case of Artificial Respiration by the Sylvester Method.

PMID- 29638518
TI  - General Council of Medical Education and Registration.

PMID- 29638517
TI  - Insanity in British Emigrants of the Middle and Upper Ranks.

PMID- 29638519
TI  - On the Employment of Hare-Lip Suture in the Treatment of Vesico-Vaginal Fistula.

PMID- 29638520
TI  - Army Medical Department.

PMID- 29638521
TI  - On the Action of the Cobra Poison.

PMID- 29638522
TI  - On the Morbid Appearances Met with in the Brains of Thirty Insane Persons.

PMID- 29638523
TI  - Case of Unilateral Paralysis Agitans.

PMID- 29638524
TI  - General Council of Medical Education and Registration.

PMID- 29638525
TI  - The Medical Council and Its Critics: A Vindication.

PMID- 29638527
TI  - Glasgow Medico-Chirurgical Society.

PMID- 29638526
TI  - Remarks on Medical Study.

PMID- 29638528
TI  - Navy Medical Department.

PMID- 29638530
TI  - Information Regarding Medical Education and Examinations.

PMID- 29638529
TI  - Army Medical School.

PMID- 29638532
TI  - Testimonial to Mr Syme.

PMID- 29638531
TI  - Indian Medical Service.

PMID- 29638533
TI  - Actual Experience in Hospital Practice of Recently Vaunted Remedies.

PMID- 29638534
TI  - List of Hospitals, Dispensaries, Etc., in Connexion with the Medical Schools of
      Scotland.

PMID- 29638535
TI  - Case of Amputation at the Ankle.

PMID- 29638536
TI  - Meetings of Societies.

PMID- 29638538
TI  - Treatment of Congestions of Erectile Organs by Hypodermic Injection of Morphia.

PMID- 29638537
TI  - On the Rare Mobility of Intra-Pelvic Parametric Phlegmon and Abscess.

PMID- 29638539
TI  - Calculus Successfully Removed from a Cavity in the Kidney, with Observations on
      the Operation of Nephrotomy.

PMID- 29638540
TI  - Case of Tumour of the Bones of the Skull.

PMID- 29638541
TI  - Case of Strangulated Hernia, with Perforation of the Bowel, in Which the
      Occlusion of the Aperture by Ligature Was Successfully Adopted.

PMID- 29638542
TI  - Traumatic Varicose Femoral Aneurism Successfully Treated by Ligature.

PMID- 29638543
TI  - The Climate of Madeira.

PMID- 29638544
TI  - Professor Syme's Observations on the Reform of Medical Education.

PMID- 29638545
TI  - Extensive Injury to the Heart in a Dog by a Pistol-Ball; Death Not Immediate.

PMID- 29638546
TI  - Address to Professor Syme from India.

PMID- 29638547
TI  - Further Observations on the Treatment of Aneurism by Iodide of Potassium, with
      Additional Cases.

PMID- 29638549
TI  - Special Clinical Meeting.

PMID- 29638548
TI  - The Alkaline Treatment of Rheumatic Fever.

PMID- 29638550
TI  - Exhibition of Patients.

PMID- 29638551
TI  - Discussion on Insomnia.

PMID- 29638552
TI  - The Musculature of the Aorta and of the Cardiac Valves, Anatomically,
      Physiologically, and Clinically Considered.

PMID- 29638553
TI  - Preparation of SiO2@Ag Composite Nanoparticles and Their Antimicrobial Activity.
AB  - At normal atmospheric temperature, the modified sol-gel method was employed to
      synthesize SiO2 nanospheres (SiO2 NSs) whose average size was about 352 nm.
      Silver nanoparticles (Ag NPs) were uniformly distributed on the surface of SiO2
      nanospheres (SiO2 NSs) by applying chemical reduction method at 95  degrees C and
      the size of silver nanoparticles (Ag NPs) could be controlled by simply tuning
      the reaction time and the concentration of sodium citrate. Besides, the size,
      morphology, structure and optical absorption properties of SiO2@Ag composite
      nanoparticles were measured and characterized by laser particle size analyzer
      (LPSA), transmission electron microscope (TEM), scanning electron microscope
      (SEM), X-ray diffraction (XRD) and ultraviolet visible absorption spectrometer
      (UV-Vis), respectively. Furthermore, antimicrobial effect experiments that
      against gram-negative bacteria (E. coli) and gram-positive bacteria (S. aureus)
      were carried out to characterize the antibacterial activity of synthesized
      SiO2@Ag composite nanoparticles. The results show that the prepared SiO2@Ag
      composite nanoparticles have strong antimicrobial activity, which is associated
      with the size of silver nanoparticles.

PMID- 29638554
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29638555
TI  - Notes on Physiology and Experimental Pathology.

PMID- 29638556
TI  - On a New Form of "Boot" for the Treatment of Talipes Equinus.

PMID- 29638558
TI  - Correspondence.

PMID- 29638557
TI  - On Suppurating Ovarian Cysts.

PMID- 29638559
TI  - Inversion of Bladder.

PMID- 29638561
TI  - Tracheotomy in Emergency.

PMID- 29638560
TI  - Intravenous Injection of Ammonia.

PMID- 29638562
TI  - The Morisonian Lectures, Delivered before the Royal College of Physicians of
      Edinburgh: Session 1874.

PMID- 29638563
TI  - Ether at Night.

PMID- 29638564
TI  - Dr Anger.

PMID- 29638565
TI  - Enlargement of the Thyroid Body in Pregnancy.

PMID- 29638566
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29638567
TI  - Distal Ligature of Carotid and Subclavin Arteries for a Case of Innominate
      Aneurism.

PMID- 29638568
TI  - Immediate Transfusion.

PMID- 29638569
TI  - Cases Illustrative of the Principles of Conservative Surgery.

PMID- 29638570
TI  - Notes on "Changed Aloin" and the Resin of Aloes.

PMID- 29638571
TI  - Clinical Lectures on Diseases of the Heart.

PMID- 29638572
TI  - Haematinuria.

PMID- 29638573
TI  - Meetings of Societies.

PMID- 29638574
TI  - Contributions to the Determination of the Diminution of the Uterus after
      Delivery.

PMID- 29638576
TI  - Maggots.

PMID- 29638575
TI  - Are the Kidneys Active Eliminators of Ether?

PMID- 29638577
TI  - Excision of an Ovarian Cyst from a Child Seven and a Half Years Old.

PMID- 29638578
TI  - Lithotomy in the Service.

PMID- 29638579
TI  - Medical News.

PMID- 29638580
TI  - Valedictory Address.

PMID- 29638581
TI  - Demonstration of Patients Wearing Artificial Limbs for Amputations at Different
      Levels in the Lower Extremity : With an Explanation and Demonstration of the Type
      of Artificial Limb Used in Each Case.

PMID- 29638582
TI  - Special Clinical Meeting.

PMID- 29638583
TI  - Internal Strangulation of the Small Intestine Caused by Bands, Adhesions, and
      Kinks.

PMID- 29638585
TI  - Simple Enlargement of the Prostate.

PMID- 29638584
TI  - Diagnosis and Prognosis in Kidney Cases by Tests for Renal Function.

PMID- 29638586
TI  - The Significance and Treatment of Glycosuria.

PMID- 29638588
TI  - Meetings of Societies.

PMID- 29638587
TI  - The Prognosis of Croupous Pneumonia in the Older Patient, with a Suggestion as to
      a Radical Modification of the Usual Plan of Treatment.

PMID- 29638589
TI  - On Two Cases of Diphtheritic Paralysis Simulating Locomotor Ataxia.

PMID- 29638590
TI  - On Rapid Pulmonary Congestion, and Pulmonary Apoplexy, as a Cause of Death after
      Surgical Operations or Injuries.

PMID- 29638592
TI  - On the Treatment of Delirium Tremens by the Hydrate of Chloral.

PMID- 29638591
TI  - On the Production of Presentation of the Face.

PMID- 29638593
TI  - Extirpation of a Kidney in Man.

PMID- 29638594
TI  - Surgery.

PMID- 29638595
TI  - Notes of an Epidemic of Typhoid Fever at Donaldson's Hospital.

PMID- 29638597
TI  - Medicine.

PMID- 29638596
TI  - Medical News.

PMID- 29638600
TI  - On a New Splint for the Knee-Joint.

PMID- 29638599
TI  - On the Action of the Cobra Poison.

PMID- 29638598
TI  - A Peculiar Paralytic Condition of the Lower Extremities Following Gastric Fever.

PMID- 29638601
TI  - Notes on the Pathology of Pneumonia and Hepatitis.

PMID- 29638602
TI  - Medical News.

PMID- 29638603
TI  - Acute Muscular Atrophy.

PMID- 29638604
TI  - Chronic Hepatic Fistula-Cure by Injection of Iodine.

PMID- 29638606
TI  - Case of Union of a Fractured Bone in a Paralyzed Limb.

PMID- 29638605
TI  - Case of Pseudo-Hypertrophic Paralysis (of Duchenne) Occurring in an Adult.

PMID- 29638607
TI  - On the So-Called Synclitic Motion of the Foetal Head in the Mechanism of
      Parturition.

PMID- 29638609
TI  - Case of Tuberculosis of the Kidneys.

PMID- 29638608
TI  - On the Causes of Endemic Fever in Lower Bengal, the Influence of Canal Irrigation
      in Their Production in Upper India, and the Means of Prevention to Be Employed.

PMID- 29638610
TI  - Meetings of Societies.

PMID- 29638611
TI  - Cases of Acute Leucocythemia in Connexion with Pregnancy.

PMID- 29638612
TI  - On the Action of the Cobra Poison.

PMID- 29638613
TI  - On Digitalis in Heart Disease.

PMID- 29638614
TI  - Vegetable Parasites.

PMID- 29638615
TI  - Red Blood-Corpuscles of Oviparous Vertebrata.

PMID- 29638616
TI  - Case of Cerebral Abscess, Consequent on Caries of Temporal Bone.

PMID- 29638617
TI  - Medical News.

PMID- 29638618
TI  - On the Cause of Intermittent and Remittent Fevers.

PMID- 29638620
TI  - Red and White Corpuscles in Blood-Stains.

PMID- 29638619
TI  - Chronic Rheumatism and Its Counterfeits.

PMID- 29638621
TI  - Elephantiasis Arabum.

PMID- 29638622
TI  - Furrows of the Nails after Sickness.

PMID- 29638623
TI  - A Few Remarks on District-Physician John Finsen's Contributions to Our Knowledge
      of the Echinococci Endemic in Iceland.

PMID- 29638624
TI  - A Case of Aphasia.

PMID- 29638625
TI  - Removal of an Embedded Uterine Fibroid.

PMID- 29638626
TI  - Case of Unclosed Urachus, with Umbilical Fistula.

PMID- 29638627
TI  - History of the Itch.

PMID- 29638628
TI  - Meetings of Societies.

PMID- 29638629
TI  - On the Treatment of Diabetes by Milk, Etc.: Being Clinical Lecture Delivered at
      the Edinburgh Royal Infirmary.

PMID- 29638630
TI  - Case of Sloughing Hernia.

PMID- 29638633
TI  - On the Action of the Cobra Poison.

PMID- 29638632
TI  - Surgery.

PMID- 29638631
TI  - On Galvano-Puncture of Naevus.

PMID- 29638634
TI  - Remarkable Case of Fibro-Nucleated or Cancroid Growth in the Pericardium.

PMID- 29638635
TI  - On Fatty Hernia.

PMID- 29638636
TI  - Commissions in the British Medical Service.

PMID- 29638637
TI  - Medical News.

PMID- 29638638
TI  - Meetings of Societies.

PMID- 29638639
TI  - Case of Diphtheritic Ophthalmia.

PMID- 29638640
TI  - On the Structural Relation between Urea and Uric Acid, Etc.

PMID- 29638641
TI  - On Croup.

PMID- 29638642
TI  - On the Action of the Cobra Poison.

PMID- 29638644
TI  - Practical Suggestions as to Medical Study: Being the Introductory Address
      Delivered at the Opening of the Medical School, Edinburgh, for the Session 1869
      70.

PMID- 29638643
TI  - Medical News.

PMID- 29638645
TI  - Meetings of Societies.

PMID- 29638646
TI  - On Polypus of the Rectum.

PMID- 29638647
TI  - Case of Removal of a Sequestrum from the Centre of the Frontal Bone, after Twenty
      Eight Years' Suffering.

PMID- 29638648
TI  - On the Condition of the Optic Disk and Retina in Acute Iritis.

PMID- 29638650
TI  - Contribution to Vital Statistics.

PMID- 29638649
TI  - Notes of Cases of Scarlet Fever.

PMID- 29638651
TI  - Periscope.

PMID- 29638652
TI  - On Aggregation in the Dublin Lying-In Hospital.

PMID- 29638653
TI  - Three Cases of Recovery from Pyaemia, in All of Which the Secondary Complications
      Had Been Distinctly Marked; with Remarks on Prognosis and Treatment.

PMID- 29638654
TI  - Effects on Antibacterial Activity and Osteoblast Viability of Non-Thermal
      Atmospheric Pressure Plasma and Heat Treatments of TiO2 Nanotubes.
AB  - The aim of this study was to evaluate the antibacterial activity against
      Porphyromonas gingivalis and osteoblast viability of heat and plasma treatment of
      TiO2 nanotubes. Specimens were divided into four groups: the Ti (polished
      titanium), Nano (TiO2 nanotube), NH 300 (heat treated at 300  degrees C on TiO2
      nanotube) and NH 400 (heat treated at 400  degrees C on TiO2 nanotube) groups.
      Antibacterial activity and osteoblast viability were evaluated in the four groups
      according to plasma treatment. Surface adhesion of Porphyromonas gingivalis was
      evaluated by crystal violet assay. Osteoblast viability was examined by XTT
      assay. Adhesion of Porphyromonas gingivalis was significantly decreased in the Ti
      group, Nano group and NH 300 group after plasma treatment (P < 0.05). Osteoblast
      viability was increased in the NH 400 group in comparison to the Ti group before
      plasma treatment (P < 0.05). Within the limitations of this study, plasma
      treatment was found to reduce the adhesion of P. gingivalis but had no influence
      on osteoblast activation.

PMID- 29638655
TI  - A Case of Oblique and Direct Inguinal Hernia Occurring on the Same Side of the
      Body.

PMID- 29638656
TI  - Medical News.

PMID- 29638657
TI  - Remarks on Taenia, and Treatment by Ethereal Extract of Male Fern in the
      Abyssinian Expedition.

PMID- 29638658
TI  - Further Observations on Arrested Twin-Development.

PMID- 29638659
TI  - On the Use of Indian Hemp in Chorea.

PMID- 29638660
TI  - Our Existing System of Hospitalism and Its Effects.

PMID- 29638661
TI  - On OEdema of the Conjunctiva as a Symptom of Surgical Fever.

PMID- 29638662
TI  - Notes on Some of the Diseases Prevalent in Victoria, Australia.

PMID- 29638664
TI  - Report of the Council of the Royal College of Physicians of Edinburgh on "The
      Nomenclature of Diseases," Drawn up by a Joint Committee Appointed by the Royal
      College of Physicians of London, and Published This Year by That College, and
      Which Is to Be Sent to Every Registered Practitioner in the United Kingdom, at
      the Expense of the Government.

PMID- 29638663
TI  - Lithotrity, with a New Lever Lithotrite.

PMID- 29638666
TI  - Appointments.

PMID- 29638665
TI  - On the Inguinal Site of Parametric Phlegmon and Abscess.

PMID- 29638667
TI  - Notes from Practice.

PMID- 29638668
TI  - Materia Medica and Therapeutics.

PMID- 29638669
TI  - Cases of Ovariotomy.

PMID- 29638670
TI  - Meetings of Societies.

PMID- 29638671
TI  - Case of Aneurism of the Descending Thoracic Aorta, Which Burst into the
      Pericardium and Left Bronchus.

PMID- 29638672
TI  - Our Existing System of Hospitalism and Its Effects.

PMID- 29638673
TI  - Surgery.

PMID- 29638674
TI  - On the Action of the Cobra Poison.

PMID- 29638675
TI  - Digitalis in Disease of the Heart.

PMID- 29638676
TI  - Observations on the Operation for Congenital Cleft Palate, with Cases.

PMID- 29638677
TI  - Case of Acute Yellow Atrophy of Liver.

PMID- 29638678
TI  - Surgery.

PMID- 29638679
TI  - Goodsir and Virchow.

PMID- 29638681
TI  - Medical News.

PMID- 29638680
TI  - Meetings of Societies.

PMID- 29638683
TI  - The Indian Medical Service.

PMID- 29638682
TI  - Case of Congenital Diaphragmatic Hernia, with Remarks.

PMID- 29638684
TI  - Naval Medical Department.

PMID- 29638685
TI  - Medicine and Pathology.

PMID- 29638686
TI  - Case of Artificial Anus, Successfully Treated by Dupuytren's Enterotome.

PMID- 29638687
TI  - Bronchial Carcinoma.

PMID- 29638689
TI  - Diet and Subacute Combined Degeneration of the Spinal Cord.

PMID- 29638688
TI  - Nephrosis.

PMID- 29638691
TI  - Paget's Disease of the Male Nipple and Areola.

PMID- 29638692
TI  - The Protection of the Child from Tuberculosis.

PMID- 29638690
TI  - The Food Disorders of Infancy.

PMID- 29638694
TI  - Post-Inflammatory Subluxation of the Atlas.

PMID- 29638693
TI  - On the Relation between the Hormones of the Anterior Lobe of the Pituitary and
      Clinical Syndromes.

PMID- 29638696
TI  - Painful Nodule of the Ear.

PMID- 29638695
TI  - Spinal Drainage in Alcoholic Deliria and Other Acute Alcoholic Psychoses.

PMID- 29638697
TI  - Neurological Notes.

PMID- 29638698
TI  - Copper Therapy of Anaemia in Infants.

PMID- 29638699
TI  - Ligation of the Palmar Arches.

PMID- 29638700
TI  - The Surgical Treatment of the Solitary Hepatoma.

PMID- 29638701
TI  - Tumours of the Cauda Equina.

PMID- 29638703
TI  - Localised Osteosclerosis.

PMID- 29638702
TI  - Vesiculitis.

PMID- 29638704
TI  - Hyperthyreoidism: A Statistical Presentation of Its Symptomatology.

PMID- 29638705
TI  - Clinical Types of Mental Deficiency in Young Children.

PMID- 29638707
TI  - Tumours of the Seminal Vesicles.

PMID- 29638706
TI  - A Study of 523 Cases of Obesity.

PMID- 29638708
TI  - Recurrence in "Benign" Giant-Cell Tumour.

PMID- 29638709
TI  - Spina Bifida Occulta and Enuresis.

PMID- 29638710
TI  - A Consideration of the Catarrhal States in Relation to Diet.

PMID- 29638712
TI  - Megacolon.

PMID- 29638711
TI  - Concussion and Memory.

PMID- 29638714
TI  - Types of Bright's Disease.

PMID- 29638713
TI  - Some Limitations of the Wassermann Reaction.

PMID- 29638715
TI  - Hypervitaminosis-D, with Report of a Fatal Case in a Child.

PMID- 29638717
TI  - The Abortive Treatment of Syphilis.

PMID- 29638716
TI  - Tumours of the Carotic Glomus.

PMID- 29638718
TI  - Spontaneous Fracture Lumbar Transverse Process.

PMID- 29638719
TI  - Fibroma of the Mesentery.

PMID- 29638720
TI  - Syphilitic Chancre of the Palpebral Conjunctiva.

PMID- 29638721
TI  - Sodium Amytal.

PMID- 29638722
TI  - Essential Hypertension-Evaluation of Therapeutic Results.

PMID- 29638723
TI  - Hirschsprung's Disease. The Report of a Case Treated by Lumbar Ganglionectomy and
      Ramisectomy.

PMID- 29638724
TI  - The Production of Orthopnoea.

PMID- 29638725
TI  - Social Psychiatry. Being the Morison Lectures for 1931 at the Royal College of
      Physicians, Edinburgh.

PMID- 29638727
TI  - Treatment of Intestinal Tuberculosis.

PMID- 29638726
TI  - The Diuretic Effect of Theocalcin in Congestive Heart Failure.

PMID- 29638728
TI  - A Further Method of Estimating the Potency of Liver Extract.

PMID- 29638730
TI  - Neurological Notes.

PMID- 29638729
TI  - Leucocyte Counts in Surgical Prognosis.

PMID- 29638731
TI  - Earphone Dermatitis.

PMID- 29638733
TI  - Dermatitis Due to Jewellery.

PMID- 29638732
TI  - Self-Inflicted Eruption Leading to Amputation of the Fingers.

PMID- 29638734
TI  - Cervical Fracture-Dislocations.

PMID- 29638735
TI  - The Autonomic Nervous System in Relation to Surgery.

PMID- 29638737
TI  - "Idiopathic" Cervical Luxation.

PMID- 29638736
TI  - Notes.

PMID- 29638738
TI  - Injuries of the Cervical Spine.

PMID- 29638739
TI  - Accessory Lateral Thyreoid Glands.

PMID- 29638740
TI  - Nodal Fever of Lendon.

PMID- 29638741
TI  - Gastric Secretion in Normal Persons.

PMID- 29638742
TI  - Otitic Hydrocephalus.

PMID- 29638743
TI  - The Boltz (A.A.S.) Test in Cerebrospinal Fluid. A Critical Review.

PMID- 29638744
TI  - Medical Education in Scotland.

PMID- 29638745
TI  - An Analysis of Bacterial Antigens on the Basis of Chemistry and Function.

PMID- 29638746
TI  - Notes.

PMID- 29638747
TI  - Unilateral Puberal Mammary Hypertrophy.

PMID- 29638748
TI  - The Convalescent State and Its Management at the Astley Ainslie Institution.

PMID- 29638750
TI  - Humility in Medicine.

PMID- 29638749
TI  - Clinical Meeting.

PMID- 29638752
TI  - The Hypochlorhydria of Asthma in Childhood.

PMID- 29638751
TI  - Gastric Tissue in the Treatment of Pernicious Anaemia.

PMID- 29638754
TI  - Note upon Ergotine, Its Inconveniences and Its Dangers.

PMID- 29638753
TI  - Cardiac Output and Oxygen Utilisation in Some Types of Heart Disease.

PMID- 29638755
TI  - Occasional Periscope of Dermatology.

PMID- 29638756
TI  - Correspondence.

PMID- 29638757
TI  - Remarks on the Diagnosis and Treatment of Scabies.

PMID- 29638758
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29638760
TI  - Modification in the Application of Sayre's Plaster-Jacket.

PMID- 29638759
TI  - Three Cases of Parametritis, with Observations on Its Diagnosis and Treatment.

PMID- 29638761
TI  - On Diastases in the Bones of the Lower Extremities of the Foetus, Produced by the
      Accoucheur.

PMID- 29638763
TI  - Meetings of Societies.

PMID- 29638762
TI  - Notes of Cases of Erysipelas Occurring during an Epidemic in the Winter 1879-80,
      and Treated in the Old Royal Infirmary.

PMID- 29638764
TI  - Notes on the Fever Which Attacked the Army of Occupation in Cyprus, 1878 to 1879.

PMID- 29638766
TI  - Monthly Retrospect of Obstetrics and Gynaecology.

PMID- 29638765
TI  - A Note on Surgical Statistics.

PMID- 29638767
TI  - Periscope of Ophthalmology.

PMID- 29638768
TI  - Periscope of Otology.

PMID- 29638769
TI  - Physics and Physic.

PMID- 29638770
TI  - Address to the Medico-Chirurgical Society of Edinburgh on January 7th.

PMID- 29638771
TI  - Periscope of Otology.

PMID- 29638773
TI  - Meetings of Societies.

PMID- 29638772
TI  - Method of Case-Taking in Gynecology.

PMID- 29638774
TI  - On a Case of Molluscum Verrucosum, Presenting Certain Unusual Features.

PMID- 29638775
TI  - Epilepsy, Vertigo, and Ear Disease.

PMID- 29638776
TI  - Occasional Periscope of Dermatology.

PMID- 29638777
TI  - Dr Farr.

PMID- 29638778
TI  - The New Edinburgh Infirmary.

PMID- 29638779
TI  - Monthly Retrospect of Obstetrics and Gynaecology.

PMID- 29638780
TI  - Correspondence.

PMID- 29638782
TI  - On the Treatment of Abortion.

PMID- 29638781
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29638783
TI  - The Causation of Some Primitive Face Cases.

PMID- 29638784
TI  - Periscope of Ophthalmology.

PMID- 29638785
TI  - Clinical Observations on the Temperature Changes, Acute Decubitis, Urinary
      Disorders, Etc., Following Fracture of the Vertebral Column.

PMID- 29638786
TI  - Case of Diphtheria Complicating Pregnancy.

PMID- 29638787
TI  - No-Pay Patients.

PMID- 29638788
TI  - Basilysis: A Suggestion for Comminuting the Foetal Head in Cases of Obstructed
      Labour.

PMID- 29638789
TI  - Meetings of Societies.

PMID- 29638790
TI  - Periscope of Syphilology.

PMID- 29638791
TI  - Ice as a Vehicle of Disease.

PMID- 29638792
TI  - Occasional Periscope of Dermatology.

PMID- 29638793
TI  - On the Position and Distention of the Female Bladder.

PMID- 29638794
TI  - General Exfoliative Dermatitis.

PMID- 29638795
TI  - On Delirium Potatorum Traumaticum.

PMID- 29638796
TI  - Absorbing Powers of Granulating Substances.

PMID- 29638797
TI  - Disturbances of Vision Produced by Poisoning by Unsound Meat.

PMID- 29638799
TI  - List of Successful Candidates for British and Indian Medical Service.

PMID- 29638798
TI  - University of Edinburgh.

PMID- 29638800
TI  - On Croup: Its Nature and Treatment.

PMID- 29638801
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29638803
TI  - Grateful Patient.

PMID- 29638802
TI  - Monthly Retrospect of Obstetrics and Gynaecology.

PMID- 29638804
TI  - Medical Pauperism.

PMID- 29638805
TI  - Report of a Case of Metro-Perimetritis Ending in Abscess of the Uterus.

PMID- 29638806
TI  - Occasional Periscope of Dermatology.

PMID- 29638807
TI  - A Case of Bilharzia Haematobia.

PMID- 29638809
TI  - Berlin International Fishery Exhibition, 1880.

PMID- 29638808
TI  - Case of Pleuro-Pneumonia.

PMID- 29638810
TI  - Address Delivered at the Opening of the Winter Session of the Edinburgh Medical
      School, October 28th, 1879.

PMID- 29638811
TI  - Observations on Some Points in Dextral Valvular Disease of the Heart, Being a
      Graduation Thesis.

PMID- 29638812
TI  - The Protection Bed and Its Uses.

PMID- 29638813
TI  - Royal College of Surgeons, Edinburgh.

PMID- 29638814
TI  - Periscope of Otology.

PMID- 29638816
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29638815
TI  - Elephantiasis Arabum.

PMID- 29638817
TI  - Meetings of Societies.

PMID- 29638819
TI  - List of Candidates for H.M. British Medical Service.

PMID- 29638818
TI  - Valedictory Address, Delivered before the Obstetrical Society of Edinburgh,
      November 12th, 1879.

PMID- 29638820
TI  - Personal Reminiscences of the International Medical Congress at Amsterdam.

PMID- 29638823
TI  - Periscope of Ophthalmology.

PMID- 29638822
TI  - University of Edinburgh.

PMID- 29638821
TI  - Monthly Retrospect of Obstetrics and Gynaecology.

PMID- 29638826
TI  - Meetings of Societies.

PMID- 29638825
TI  - Monthly Retrospect of Obstetrics and Gynaecology.

PMID- 29638824
TI  - Correspondence.

PMID- 29638828
TI  - Case of Resuscitation of New-Born Infant.

PMID- 29638827
TI  - Report of the Edinburgh Royal Maternity and Simpson Memorial Hospital for the
      Quarter Ending 31st January 1880.

PMID- 29638829
TI  - Edinburgh Royal Maternity and Simpson Memorial Hospital.

PMID- 29638830
TI  - Correspondence.

PMID- 29638831
TI  - Correspondence.

PMID- 29638832
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29638833
TI  - Periscope of Ophthalmology.

PMID- 29638834
TI  - Notes of a Case of Death during the Administration of Chloroform; with Remarks as
      to the Possible and Probable Causes of Death.

PMID- 29638835
TI  - Nurses and Doctors.

PMID- 29638837
TI  - Minto House Medical School.

PMID- 29638836
TI  - Animal Vaccination.

PMID- 29638838
TI  - Periscope of Otology.

PMID- 29638839
TI  - On a Labour Obstructed from an Unusual Cause.

PMID- 29638840
TI  - Jugular Reflux and Tricuspid Regurgitation.

PMID- 29638841
TI  - On the Rate of Cooling of the Human Body after Death.

PMID- 29638843
TI  - On Intrauterine Puerperal Coagula.

PMID- 29638842
TI  - Quarterly Report of Royal Maternity and Simpson Memorial Hospital.

PMID- 29638844
TI  - Vaccination Notes and Recollections.

PMID- 29638845
TI  - Laryngismus Stridulus, or Tetany.

PMID- 29638846
TI  - Monthly Retrospect of Obstetrics and Gynaecology.

PMID- 29638847
TI  - The Protection Bed and Its Uses.

PMID- 29638848
TI  - Observations on Some Points in Dextral Valvular Disease of the Heart, Being a
      Graduation Thesis.

PMID- 29638850
TI  - A Doctor's Use of the Carrier Pigeon.

PMID- 29638849
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29638851
TI  - Elephantiasis Arabum.

PMID- 29638853
TI  - Case of Pleuro-Pneumonia.

PMID- 29638852
TI  - On Medical Education in Spain.

PMID- 29638854
TI  - Meetings of Societies.

PMID- 29638855
TI  - Periscope of Ophthalmology.

PMID- 29638856
TI  - Periscope of Otology.

PMID- 29638857
TI  - On Local Hygienic Influences.

PMID- 29638858
TI  - Claws of Felidae.

PMID- 29638859
TI  - Extracts from Harveian Address of 1874.

PMID- 29638860
TI  - Royal Edinburgh Asylum Papers. Hemiplegia in Relation to Insanity.

PMID- 29638861
TI  - On the Occasional Arrestive and Discutient Influence of Pregnancy over Pelvi
      Abdominal Tumours.

PMID- 29638862
TI  - Comparative Anatomy of the Arterial Cerebral Circulation in Animals and the Human
      Subject, as Bearing on Parturient Apoplexy and Convulsions.

PMID- 29638863
TI  - Meetings of Societies.

PMID- 29638864
TI  - On a Simple Apparatus for the Estimation of Urea by the Nitrogen Process.

PMID- 29638866
TI  - An Obstetric History : A Vesico-Vaginal Fistula, with Subsequent Conceptions.

PMID- 29638865
TI  - Treatment of Exostosis by Subcutaneous Fracture.

PMID- 29638867
TI  - Dr Taylor's Paper.

PMID- 29638868
TI  - Medical News.

PMID- 29638869
TI  - Medical News.

PMID- 29638871
TI  - The Relation of the Cranial Contents to the Pressure of the Atmosphere.

PMID- 29638870
TI  - Effects of Improved Sanitary Arrangements on the Mortality of the Town of Leven.

PMID- 29638872
TI  - An Unnatural Position of the Head a Cause of Death from Chloroform and Other
      Anaesthetics.

PMID- 29638873
TI  - Treatment of Burns.

PMID- 29638874
TI  - Case of Poisoning by the Inhalation of Coal-Gas.

PMID- 29638875
TI  - Case of Fibroid of the Uterus, Complicating Pregnancy, and Proving Fatal by
      Torsion of the Pedicle.

PMID- 29638876
TI  - Case of Cystic Tumour Attached to Kidney Simulating Ovarian Disease; Extirpation
      of Kidney; Recovery.

PMID- 29638877
TI  - On the Influence of Anaemia on the Nutrition of the Muscles of the Heart.

PMID- 29638878
TI  - Notes on Congenital Absence of the Kidney.

PMID- 29638879
TI  - Syphilitic Multiple Herpetiform Chancre.

PMID- 29638880
TI  - Esmarch's "Bloodless Method" Employed for the Excision of a Scrotal Tumour.

PMID- 29638881
TI  - A Case of Pregnancy in a Rudimentary Horn of the Uterus; Death by Haemorrhage;
      Transmigratio Seminis Extrauterina.

PMID- 29638882
TI  - The Fungus of Alopecia Areata.

PMID- 29638883
TI  - Oxygen for Aeronauts.

PMID- 29638884
TI  - Jaborandi.

PMID- 29638885
TI  - Medical News.

PMID- 29638886
TI  - Note of a Case of Recurrent Peculiar Transverse Presentation, Apparently Due to
      Malformation of the Uterus.

PMID- 29638887
TI  - On Section of the Buccal Nerve from the Mouth.

PMID- 29638888
TI  - Case of Absorption of an Exostosis.

PMID- 29638889
TI  - Physiological Papers: Comparative Observations on the Physiological Action of
      Chloral and Bromal Hydrates, and Iodoform.

PMID- 29638890
TI  - Meetings of Societies.

PMID- 29638891
TI  - On the Surgical Use of Gastric Juice in the Treatment of Cancerous Tumours.

PMID- 29638892
TI  - Triple Amputation.

PMID- 29638893
TI  - Royal Edinburgh Asylum Papers. On Two Cases of Infantile Paralysis, Followed by
      Epilepsy and Insanity.

PMID- 29638894
TI  - On the Non-Existence of Pressure on, or Compression of, the Brain.

PMID- 29638895
TI  - List of Hospitals, Dispensaries, Etc., in Connexion with the Medical Schools of
      Scotland.

PMID- 29638896
TI  - Case of Mechanical Obstruction to the Flow of Urine for Eleven Days.

PMID- 29638897
TI  - Observations upon the Nature and Treatment of Difficult Occipito-Posterior
      Positions of the Head, Founded upon an Analysis of Twenty-Six Operative Cases.

PMID- 29638898
TI  - Epidemic of Dengue in the Island of Mauritius, in 1873.

PMID- 29638899
TI  - Information Regarding Medical Education and Examinations.

PMID- 29638900
TI  - Indian Medical Service.

PMID- 29638901
TI  - Army Medical Department.

PMID- 29638902
TI  - Army Medical School.

PMID- 29638903
TI  - Medical News.

PMID- 29638904
TI  - Chloral for Anatomical Injections.

PMID- 29638905
TI  - Fournier on Syphilitic Gummata.

PMID- 29638906
TI  - Note of a Case of Temporary Loss of Voluntary Power, Produced by a Touch on the
      Head.

PMID- 29638908
TI  - Preliminary Examinations for the Diplomas of the Royal Colleges of Physicians and
      Surgeons of Edinburgh, during the Year 1873-74.

PMID- 29638907
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29638909
TI  - Coccobacteria Septica.

PMID- 29638910
TI  - Navy Medical Department.

PMID- 29638911
TI  - Royal Edinburgh Asylum Papers: Clinical Notes (1.) On a Case of Microcephaly;
      (2.) On a Case of General Paralysis of the Insane of Unusually Long Duration.

PMID- 29638912
TI  - Limitation of Examinations.

PMID- 29638913
TI  - Address to the Edinburgh Medical Graduates.

PMID- 29638914
TI  - Dislocation Forwards of the Styloid End of the Ulna.

PMID- 29638916
TI  - Medical News.

PMID- 29638915
TI  - Correspondence.

PMID- 29638917
TI  - The Causes of Death among the Assured of the Scottish Widows' Fund Life Assurance
      Society, from 1867 to 1873 Inclusive.

PMID- 29638920
TI  - Gastrotomy.

PMID- 29638919
TI  - The Treatment of Intestinal Obstruction.

PMID- 29638918
TI  - University Graduation.

PMID- 29638923
TI  - The Morisonian Lectures, Delivered before the Royal College of Physicians of
      Edinburgh: Session 1874.

PMID- 29638922
TI  - A Case of Strangulated Hernia Successfully Treated by Pneumatic Aspiration.

PMID- 29638921
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29638925
TI  - On the Digestibility of the Gelatine-Yielding Tissues.

PMID- 29638924
TI  - Royal Edinburgh Asylum Papers: Mania a Potu.

PMID- 29638926
TI  - To the Knowledge of the Minute Pathology of Abdominal Typhus.

PMID- 29638928
TI  - Meetings of Societies.

PMID- 29638927
TI  - Erratum in the November Number of the Journal.
AB  - [This corrects the article on p. 414 in vol. 20.].

PMID- 29638929
TI  - Medical News.

PMID- 29638931
TI  - A New Pneumatic Aural Speculum.

PMID- 29638930
TI  - The Mechanism of Hearing.

PMID- 29638932
TI  - Lawrie on the Temperature in Health.

PMID- 29638933
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29638934
TI  - Upon the Medicinal Properties of Silica in Cancer, Fibroid Tumours, and Diabetes.

PMID- 29638935
TI  - On the Physical Exploration of the Lungs.

PMID- 29638936
TI  - Exostoses of the External Auditory Meatus.

PMID- 29638937
TI  - Notes on the Case of a Woman Who Swallowed a Pint of Paraffin-Oil.

PMID- 29638938
TI  - Royal Edinburgh Asylum Papers: Case of Determined Suicidal Melancholia.

PMID- 29638939
TI  - Atrophy of the Ossicula of the Ear as Well as of the Membrana Tympani.

PMID- 29638940
TI  - On the Pecuniary Value of the Emoluments and Pensions of Army Medical Officers.

PMID- 29638941
TI  - Medical News.

PMID- 29638942
TI  - The Morisonian Lectures, Delivered before the Royal College of Physicians of
      Edinburgh: Session 1874.

PMID- 29638943
TI  - A New Operation for Aneurism.

PMID- 29638944
TI  - A Case of Direct Arterial Blood-Transfusion from Animals.

PMID- 29638945
TI  - Note on the Carbolic Acid Mode of Dressing Wounds (Lister's Process), and on the
      Development of Vibrios in the Wounds.

PMID- 29638946
TI  - Case of Sciatica Depending on Pressure by an Intrapelvic Tumour.

PMID- 29638947
TI  - The Resistance of the Vascular Walls in a Normal Condition and during
      Inflammation.

PMID- 29638948
TI  - Correspondence.

PMID- 29638949
TI  - On Two Cases of Muscular Atrophy Observed in the Course of General Paralysis.

PMID- 29638950
TI  - On the Different Action of Coffein on the Rana Temporaria and the Rana Esculenta.

PMID- 29638951
TI  - Two Victims of Hydrophobia.

PMID- 29638952
TI  - Fracture of the Styloid Process of the Ulna.

PMID- 29638953
TI  - Excision of Scapula: Contribution to the History of Complete Removal of Scapula,
      with Preservation of the Arm. Operation Followed by Success, Lasting Five Years
      and Four Months.

PMID- 29638954
TI  - Correspondence.

PMID- 29638955
TI  - Circumcision.

PMID- 29638957
TI  - Spontaneous Fractures in Patients Suffering from Ataxia.

PMID- 29638956
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29638958
TI  - Researches on Bone-Absorption and Giant Cells.

PMID- 29638960
TI  - Ueber Cysten an der hinteren Blasenwand bei Mannern.

PMID- 29638959
TI  - Case of Preputial Calculus.

PMID- 29638961
TI  - Asiatic Cholera.

PMID- 29638962
TI  - Clinical Lectures on Diseases of the Heart.

PMID- 29638963
TI  - On the Minute Anatomy of Muscle and Tendon, and Some Notes Regarding the
      Structure of the Cornea.

PMID- 29638964
TI  - Notes of a Case of Chylous Urine.

PMID- 29638966
TI  - Meetings of Societies.

PMID- 29638965
TI  - Case of Sudden Death from Angina Pectoris, with Remarks.

PMID- 29638967
TI  - Tracheotomy for Foreign Body.

PMID- 29638969
TI  - Medical News.

PMID- 29638968
TI  - Notes of Some Recent Surgical Cases Bearing on Legal Medicine.

PMID- 29638971
TI  - Aberrant Familial Diphtheria.

PMID- 29638970
TI  - Hermaphroditismus Verus Lateralis.

PMID- 29638972
TI  - Psychiatry and Race Betterment.

PMID- 29638973
TI  - Hypoglycaemia.

PMID- 29638974
TI  - Constancy of the Day-To-Day Leucocyte Blood Count.

PMID- 29638975
TI  - The Problem of Stuttering: The Present Position.

PMID- 29638976
TI  - Ganglionectomy and Sciatica.

PMID- 29638978
TI  - The Diagnostic and Therapeutic Use of Tuberculin in Certain Ocular Conditions.

PMID- 29638977
TI  - Studies on Prenatal Lesions of Striated Muscle as a Cause of Congenital
      Deformity: I.-Congenital Tibial Kyphosis. II.-Congenital High Shoulder. III.
      Myodystrophia Foetalis Deformans.

PMID- 29638979
TI  - Notes on a Series of Thirty-Seven Cases of Chronic B. coli Cystitis.

PMID- 29638981
TI  - Notes.

PMID- 29638980
TI  - Ovarian Autografting.

PMID- 29638982
TI  - The Alkali Reserve and Fat-Content of the Blood.

PMID- 29638983
TI  - OEsophageal Reconstruction.

PMID- 29638984
TI  - Myoma of the Rectum.

PMID- 29638985
TI  - The Tuberculous Nature of Phlyctenular Keratoconjunctivitis.

PMID- 29638986
TI  - Pigmentation of Pregnancy.

PMID- 29638987
TI  - The Treatment of Pulmonary Tuberculosis by Artificial Pneumothorax and Other
      Methods of Collapse.

PMID- 29638988
TI  - Simultaneous Medial and Lateral Dislocation of the Clavicle.

PMID- 29638989
TI  - The Treatment of Acute Rheumatism by Streptococcus Antitoxin.

PMID- 29638990
TI  - Acute Appendicitis: A Statistical Survey of 8000 Cases.

PMID- 29638991
TI  - Operation in Metastatic Cerebral Carcinoma.

PMID- 29638992
TI  - Transplantation of Heterogenous Bone in Hypocalcaemia.

PMID- 29638993
TI  - Some Problems of Dermatitis.

PMID- 29638994
TI  - Resorbable Metal Nails in Fractures.

PMID- 29638995
TI  - Syphilis among the Buriats.

PMID- 29638996
TI  - Diabetes Mellitus and Pregnancy.

PMID- 29638997
TI  - On the Mechanism of Sodium Depletion in Addison's Disease.

PMID- 29638998
TI  - Evipan Anaesthesia.

PMID- 29638999
TI  - Type II Auriculo-Ventricular Block: And the Role of Digitalis in the AEtiology of
      Auriculo-Ventricular Block.

PMID- 29639000
TI  - Appendicular Varicocele.

PMID- 29639001
TI  - Malakoplakia of the Urinary Bladder: Report of a Case.

PMID- 29639002
TI  - Diet of Tuberculous and Non-Tuberculous Children.

PMID- 29639004
TI  - Aortic Aneurysm Simulating Thrombophlebitis.

PMID- 29639003
TI  - Clinical Meeting.

PMID- 29639005
TI  - Peripheral Neuritis. The Morrison Lectures, 1932, Delivered before the Royal
      College of Physicians of Edinburgh, May 1932.

PMID- 29639006
TI  - Some Medical Heroes of the 17th, 18th, and 19th Centuries.

PMID- 29639007
TI  - The Diagnosis and Treatment of Neurosyphilis.

PMID- 29639008
TI  - Notes.

PMID- 29639009
TI  - Continuous Intravenous Infusion.

PMID- 29639010
TI  - Hernia of the Ligamentum Teres Hepatis.

PMID- 29639011
TI  - Pregnancy and Diabetes.

PMID- 29639012
TI  - Medical Education in Scotland.

PMID- 29639013
TI  - The Association of Adams-Stokes Attacks with Cheyne-Stokes Respiration: With a
      Case Report.

PMID- 29639014
TI  - The After-Effects of Head Injury.

PMID- 29639015
TI  - Amoebiasis and the Autonomic Nervous System.

PMID- 29639016
TI  - Notes.

PMID- 29639018
TI  - The Classification and Treatment of Anaemia, with Special Reference to the
      Nutritional Factor.

PMID- 29639017
TI  - Sweat Gland Carcinoma of the Breast: A Morpho-Histological Study.

PMID- 29639019
TI  - Occupational Dermatitis Due to Arsenic.

PMID- 29639021
TI  - Gastro-Intestinal Allergy.

PMID- 29639020
TI  - Studies on Blood and Tissue Reactions: IV. The Peripheral Blood Picture is the
      Image of the Focal Lesion.

PMID- 29639022
TI  - A Fatal Case of Lead Poisoning Due to a Hair Dye.

PMID- 29639023
TI  - Spondylitis and Innervation.

PMID- 29639024
TI  - The Medical History of Sir Walter Scott.

PMID- 29639026
TI  - Forced Water Drinking in Epileptic Children.

PMID- 29639025
TI  - The Classification and Treatment of Anaemia, with Special Reference to the
      Nutritional Factor.

PMID- 29639027
TI  - Spontaneous Cure of Arterio-Venous Aneurysm.

PMID- 29639028
TI  - Sir Walter Scott and Res Medica.

PMID- 29639029
TI  - The Cephalic Features of Sir Walter Scott.

PMID- 29639031
TI  - Notes.

PMID- 29639030
TI  - Toxic Goitre: A Survey of Cases Treated during Ten Years.

PMID- 29639032
TI  - Haemorrhagic Bright's Disease.

PMID- 29639034
TI  - Persistent Flexion of the Thumb.

PMID- 29639033
TI  - Coeliac Disease in the Adult.

PMID- 29639035
TI  - Bilateral Carcinoma Mammae.

PMID- 29639036
TI  - Obesity Osteoporosis.

PMID- 29639037
TI  - Splenomegalic Arthropathy.

PMID- 29639038
TI  - Suppression of Urine and Deficiency of Renal Secretion.

PMID- 29639039
TI  - Bone Transplantation in Spinal Deformity.

PMID- 29639040
TI  - Intramammary Angeioma.

PMID- 29639042
TI  - Maxillary Hyperostosis.

PMID- 29639041
TI  - Congenital Air-Cysts of the Lung.

PMID- 29639043
TI  - A Histological Study of the Normal Mamma in Relation to Tumour Growth. I.-Early
      Development to Maturity.

PMID- 29639044
TI  - Fracture of the Femur: A Statistical Analysis of 285 Cases.

PMID- 29639045
TI  - Recurrent Bleeding from the Eyes.

PMID- 29639047
TI  - Enostoses.

PMID- 29639046
TI  - Non-Specific Protein Therapy in Rheumatic Conditions.

PMID- 29639048
TI  - Ligation of the Right and Left Gastric Arteries in Carcinoma and Ulcer of the
      Stomach.

PMID- 29639049
TI  - Passage of a Needle through the Heart.

PMID- 29639051
TI  - Dermoid Cysts of the Anterior Abdominal Wall.

PMID- 29639050
TI  - Notes.

PMID- 29639052
TI  - Peripheral Neuritis. The Morrison Lectures, 1932, Delivered before the Royal
      College of Physicians of Edinburgh, May 1932.

PMID- 29639053
TI  - Clinical Meeting.

PMID- 29639055
TI  - Hereditary Familial Telangiectasia.

PMID- 29639054
TI  - Peripheral Neuritis. The Morison Lectures, 1932, Delivered before the Royal
      College of Physicians of Edinburgh, May 1932.

PMID- 29639056
TI  - Notes.

PMID- 29639057
TI  - The Report of an Investigation into the Process of the Healing of Fractured
      Bones, with Some Clinical Applications.

PMID- 29639058
TI  - Malignant Disease of the Breast. A Statistical Survey of 1000 Case Records.

PMID- 29639059
TI  - Lipoidproteinosis.

PMID- 29639060
TI  - Septic Maxillary Periostitis in Infants.

PMID- 29639061
TI  - Cheloid and Acne Cheloid.

PMID- 29639062
TI  - Traumatic Fat Embolism.

PMID- 29639063
TI  - A Study of Peptic Ulcer.

PMID- 29639065
TI  - Blindness from Haemorrhage.

PMID- 29639064
TI  - Medical Education in Scotland.

PMID- 29639066
TI  - The National Consumption of Carbohydrates in Relation to Disease.

PMID- 29639068
TI  - Notes.

PMID- 29639067
TI  - The Human Heart in Anaesthesia. An Electrocardiographic Study.

PMID- 29639069
TI  - Post-Traumatic Stretching of Ligaments.

PMID- 29639071
TI  - Stenosing Tendovaginitis.

PMID- 29639070
TI  - Cinematograph Demonstration.

PMID- 29639072
TI  - Medical Notes about Shakespere and His Times: Being the Harveian Address to the
      Edinburgh Society, on April 12, 1875.

PMID- 29639073
TI  - The Temperature of the Uterus.

PMID- 29639074
TI  - Ovariotomy beyond the Indus.

PMID- 29639075
TI  - Meetings of Societies.

PMID- 29639076
TI  - Attack of Hysteria in a Man, Treated and Cured by Compression of the Testicles.

PMID- 29639077
TI  - Experimental Investigations into the Growth of Long Bones in Pathological
      Conditions.

PMID- 29639079
TI  - On the Influence of Chloral Hydrate on the Excitability of the Nervous System to
      Stricker's Jahrbucher.

PMID- 29639078
TI  - Notes on "Changed Aloin" and the Resin of Aloes.

PMID- 29639080
TI  - Gesellschaft der Aerzte.

PMID- 29639081
TI  - Cases of Fatal Haemorrhage after Childbirth.

PMID- 29639082
TI  - Report of and Observations upon a Case of Puerperal Tetanus.

PMID- 29639083
TI  - Correspondence.

PMID- 29639084
TI  - Method of Increasing the Power of the Operator in Cases of Delivery by Forceps.

PMID- 29639085
TI  - Four Cases of Infection from Vaccine Lymph, and Fatal Termination.

PMID- 29639086
TI  - Wound of the Liver.

PMID- 29639088
TI  - Midwives and Puerperal Fever.

PMID- 29639087
TI  - Glimpses at the Health Resorts of the Bay of Naples in Ancient and Modern Times.

PMID- 29639089
TI  - On the Treatment of Certain Cases of Stricture of the Urethra by a Combination of
      Internal and External Division.

PMID- 29639091
TI  - The Aleppo Evil or Button.

PMID- 29639090
TI  - Note on Intrauterine Craniometry.

PMID- 29639092
TI  - Periscope.

PMID- 29639093
TI  - A Case of Intrauterine Fibrous Polypus.

PMID- 29639094
TI  - La Transfusione del Sangue negli alienati.

PMID- 29639095
TI  - On the Means of Ascertaining the Length of Gestation by Measurements of the
      Foetus and Gravid Uterus during the Second Period of Pregnancy.

PMID- 29639096
TI  - Notes and Observations on a Case of Poisoning by Aconite.

PMID- 29639098
TI  - Ascites: Recovery after Paracentesis Had Been Performed One Hundred and Thirty
      Three Times.

PMID- 29639097
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29639099
TI  - Iodide of Potassium in Aneurism.

PMID- 29639100
TI  - Researches into the Mode of Action of the Emetics Most Commonly Used.

PMID- 29639101
TI  - Bloodless Surgery.

PMID- 29639102
TI  - Meetings of Societies.

PMID- 29639103
TI  - The Temperature of the External Ear in Physiological and in Pathological
      Conditions.

PMID- 29639104
TI  - On the Risks Run by Obstetricans.

PMID- 29639105
TI  - MM. Budin and Coyne.

PMID- 29639106
TI  - The Morisonian Lectures, Delivered before the Royal College of Physicians of
      Edinburgh: Session 1874.

PMID- 29639107
TI  - Case of Poisoning by Strychnia, Treated by Chloral Hydrate, and Followed by
      Recovery.

PMID- 29639108
TI  - Notes on the Grouse Disease.

PMID- 29639110
TI  - Fournier on Syphilitic Gummata.

PMID- 29639109
TI  - On Prolapsus and Retroversion as Alternating Misplacements of the Gravid Uterus.

PMID- 29639113
TI  - The Morisonian Lectures, Delivered before the Royal College of Physicians of
      Edinburgh: Session 1874.

PMID- 29639111
TI  - Medical News.

PMID- 29639112
TI  - On Local Hygienic Influences.

PMID- 29639115
TI  - Medical News.

PMID- 29639114
TI  - Antiseptic Incisions and Aid to Surgical Diagnosis.

PMID- 29639116
TI  - Change of Wet-Nurses.

PMID- 29639118
TI  - To Correspondents.

PMID- 29639117
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29639119
TI  - Meetings of Societies.

PMID- 29639121
TI  - Dr Dougall's Treatment of Leprosy with Gurjun-Oil.

PMID- 29639120
TI  - Edinburgh Asylum Papers: Cases Illustrating the Effect of Peripheral Irritations
      in Epilepsy.

PMID- 29639123
TI  - Fournier on Syphilitic Gummata.

PMID- 29639122
TI  - On the Influence of Mercurial Preparations on the Richness of the Blood in Red
      and White Globules.

PMID- 29639124
TI  - Suppression of Urine.

PMID- 29639125
TI  - Inaugural Address to the Royal Medical Society of Edinburgh at the Opening of the
      137th Session.

PMID- 29639126
TI  - Notes of a Case of Abscess of the Liver.

PMID- 29639127
TI  - Correspondence.

PMID- 29639128
TI  - The Morisonian Lectures, Delivered before the Royal College of Physicians of
      Edinburgh: Session 1874.

PMID- 29639129
TI  - On Two Cases of Anchylosis of the Knee-Joint Treated bg Osteotomy.

PMID- 29639130
TI  - On the Treatment of Secondary Syphilis.

PMID- 29639131
TI  - Cases in Medical Jurisprudence.

PMID- 29639132
TI  - The Death-Rate in Glasgow-The Debate at the Police Board.

PMID- 29639133
TI  - Glimpses at the Health Resorts of the Bay of Naples in Ancient and Modern Times.

PMID- 29639134
TI  - The Result of a Series of Experiments.

PMID- 29639135
TI  - Case of Salivary Calculus in the Parotid Duct.

PMID- 29639137
TI  - Meetings of Societies.

PMID- 29639136
TI  - Chloral Hydrate in the Treatment of the So-Called Dry Chronic Catarrh of the
      Middle Ear.

PMID- 29639138
TI  - On a Case of Necrosis of the Jaws from Phosphorus.

PMID- 29639139
TI  - Case of Suppurative Pericarditis.

PMID- 29639141
TI  - Abortive Treatment of Gonorrhaea.

PMID- 29639140
TI  - Correspondence.

PMID- 29639143
TI  - In Variola.

PMID- 29639142
TI  - Chemical Vapours, Fog, and the Death-Rate.

PMID- 29639145
TI  - Medical News.

PMID- 29639144
TI  - M. Malassez.

PMID- 29639146
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29639147
TI  - Case of Hydrocystis Capitis, Occurring in a Child after Birth.

PMID- 29639148
TI  - M. Malassez.

PMID- 29639149
TI  - Description of a Diprosopus Triophthalmus Monster.

PMID- 29639151
TI  - Meetings of Societies.

PMID- 29639150
TI  - Eucalyptus Globulus.

PMID- 29639152
TI  - On Prickle Cells in the Capsule of a Fibrous Polypus of the Uterus.

PMID- 29639153
TI  - Reply to above.

PMID- 29639154
TI  - Clinical Lectures on Diseases of the Heart.

PMID- 29639155
TI  - In Vitro Study on the Plasma-Polymerization of Propionaldehyde and Allylglycidyl
      Ether for Immobilization of Recombinant Human Bone Morphogenetic Protein-2.
AB  - In this study, recombinant human bone morphogenetic protein-2 (rhBMP-2) was
      directly immobilized on the plasma-polymerized propionaldehyde (PA) and
      allylglycidyl ether (AGE) surface through the imine bonding and epoxy-amine
      bonding, respectively. Aldehyde and epoxide plasma-polymerization were carried
      out at plasma power 60 W for 10 min and monomers were used to PA and AGE. After
      the plasma-polymerization and rhBMP-2 immobilization, substrate surfaces were
      characterized by contact angle, field emission scanning electron microscopy, and
      attenuated total reflectance Fourier transform infrared. In addition, the
      biological activities of MC3T3-E1 cells were evaluated by initial adhesion and
      alkaline phosphate (ALP) activity. The rhBMP-2 immobilized PA and AGE surfaces
      promoted significantly higher ALP activity of MC3T3-E1 cells than pristine
      surface.

PMID- 29639157
TI  - The Treatment of Tetanus.

PMID- 29639156
TI  - Vital Staining Methods in the Diagnosis, Prognosis and Treatment of Medical and
      Surgical Conditions.

PMID- 29639158
TI  - Fractures of the Lumbar Transverse Processes.

PMID- 29639160
TI  - Latent Hypernephroma.

PMID- 29639159
TI  - The Increase in the National Cancer Death-Rate and Its Causation.

PMID- 29639161
TI  - Diplopia without Extra-Ocular Palsies, Caused by Heteronymous Defects in the
      Visual Fields Associated with Defective Macular Vision.

PMID- 29639163
TI  - Diverticulum Ilei (Meckel) within the Layers of the Mesentery.

PMID- 29639162
TI  - Macroglossia.

PMID- 29639164
TI  - Post-Operative Motor Paralysis of the Femoral Nerve.

PMID- 29639165
TI  - Subacute Combined Degeneration of the Cord: Symptomatology and Effects of Liver
      Therapy.

PMID- 29639166
TI  - A Classification of Bright's Disease.

PMID- 29639167
TI  - Sternotomy in Mediastinal Tumours.

PMID- 29639168
TI  - Cystadenoma of the Liver.

PMID- 29639169
TI  - Secondary Carcinoma of the Lung with Inconspicuous Primary in the Gall-Bladder.

PMID- 29639170
TI  - Simple Ulcer Small Intestine.

PMID- 29639171
TI  - Classification of Tumours.

PMID- 29639172
TI  - Phrenicectomy.

PMID- 29639173
TI  - Local Lipodystrophy Following Insulin Injections.

PMID- 29639174
TI  - Connective Tissue Tumour of Blood Vessel Sheath.

PMID- 29639176
TI  - Thanatophoric Fish.

PMID- 29639175
TI  - Prolonged Retention of a Vaginal Pessary.

PMID- 29639177
TI  - Adult Ringworm of the Scalp.

PMID- 29639178
TI  - Urachal Fistulae.

PMID- 29639179
TI  - The Clinical Features of Myocardial Infarction.

PMID- 29639180
TI  - Imperforate Vagina-Urethral Coitus.

PMID- 29639181
TI  - Bullet Embedded in the Diaphragm.

PMID- 29639182
TI  - A Case of Purpura Annularis Telangiectodes.

PMID- 29639184
TI  - Tuberculous Cranial Osteitis.

PMID- 29639183
TI  - Nephrectomy in the Kyphotic.

PMID- 29639185
TI  - Iliac Embolectomy.

PMID- 29639186
TI  - A Case of Microcephaly Following Embryonic Roentgen Irradiation.

PMID- 29639187
TI  - Experimental Diabetes Insipidus.

PMID- 29639189
TI  - Notes.

PMID- 29639188
TI  - Case of Acute Pneumonic Phthisis Becoming Chronic, Characterised by Complete
      Absence of Cough in the Acute Stage.

PMID- 29639190
TI  - Post-Vaccination Encephalitis.

PMID- 29639191
TI  - Uroselectan: Excretion Urography.

PMID- 29639192
TI  - Hydrophobia.

PMID- 29639194
TI  - Spinal Symptoms in Chloroma and Leukaemia.

PMID- 29639193
TI  - Post-Operative Pulmonary Collapse.

PMID- 29639195
TI  - Acetylcholine in Arterial Spasm.

PMID- 29639196
TI  - The Cutireaction Test for Hydatid Cysts.

PMID- 29639197
TI  - Tuberculosis in Children.

PMID- 29639198
TI  - The Nirvanol Treatment of Chorea.

PMID- 29639199
TI  - Sarcoma and Radiotherapy.

PMID- 29639200
TI  - Notes.

PMID- 29639201
TI  - The Analogy of Black Colostrum to Melanhidrosis, with Some Remarks on Coloured
      Milk and Coloured Sweat.

PMID- 29639202
TI  - Melanogenesis: A Review.

PMID- 29639204
TI  - An Experience with Avertin Anaesthesia in Gynaecology.

PMID- 29639203
TI  - On the Nature and Structure of the Suprarenal Cortex.

PMID- 29639206
TI  - Osteocartilaginous Bodies in Tendon Sheaths.

PMID- 29639205
TI  - Cardiac Output in Hyperthyreoidism.

PMID- 29639207
TI  - The Corpus Callosum and Its Tumours.

PMID- 29639208
TI  - Preliminary Note on Blood Pressure during Avertin Anaesthesia.

PMID- 29639209
TI  - Tumours of the Pineal, Corpora Quadrigemina and Third Ventricle: The Inter
      Relationship of Their Syndromes and Their Surgical Treatment.

PMID- 29639211
TI  - Medical News.

PMID- 29639210
TI  - Medical Education in Scotland.

PMID- 29639212
TI  - On the Physiology of the Circulation in Plants, in the Lower Animals, and in Man.

PMID- 29639214
TI  - Tracheotomy by the Galvanic Cautery.

PMID- 29639213
TI  - Meetings of Societies.

PMID- 29639215
TI  - On an Epidemic of Diphtheria Observed at Naples in 1871, with an Attempt to
      Determine the Common Origin of Cerebro-Spinal Meningitis, Typhoid Fever, and
      Diphtheria.

PMID- 29639216
TI  - Cases of Poisoning by Strychnia.

PMID- 29639217
TI  - On a Substitute for Animal Food, in Convalescence, in Certain Disorders of the
      Stomach, and for Poor People.

PMID- 29639218
TI  - On the Feeding of the Insane.

PMID- 29639220
TI  - Intermuscular Injections of Muriate of Morphia in Tetanus.

PMID- 29639219
TI  - Asthenic Insanity.

PMID- 29639221
TI  - The Swelled Leg of Fevers.

PMID- 29639222
TI  - Medical News.

PMID- 29639223
TI  - The Anti-Malarial and Other Therapeutic Properties of Eucalyptus Globulus.

PMID- 29639224
TI  - Successful Case of Amputation at the Hip-Joint for Cancerous Tumour of Femur.

PMID- 29639225
TI  - Case of Puerperal Convulsions.

PMID- 29639226
TI  - On the Physiology of the Circulation in Plants, in the Lower Animals, and in Man.

PMID- 29639227
TI  - Meetings of Societies.

PMID- 29639228
TI  - Dissection of Malformed Foetus Having Deficiency of Anterior Abdominal Wall.

PMID- 29639229
TI  - Medical News.

PMID- 29639230
TI  - Dystocia: The Exact Diagnosis of the Placental Position in Placenta Praevia by
      Vaginal Stethoscopy, and a Direct Mode of Haemostatic Treatment.

PMID- 29639232
TI  - Epilepsy Treated by Bromide of Potassium.

PMID- 29639231
TI  - Hypochondriasis: Its Nature and Treatment.

PMID- 29639234
TI  - Amputation after Injury, in the Country.

PMID- 29639233
TI  - Treatment of Retention of Urine.

PMID- 29639235
TI  - Notes of a Case of Persistent Priapism.

PMID- 29639236
TI  - Notes of a Recent Epidemic of Typhoid Fever, and Its Mode of Propagation.

PMID- 29639237
TI  - The Physiological Action of Chloral, Illustrated by Experiments.

PMID- 29639238
TI  - On the Physiology of the Circulation in Plants, in the Lower Animals, and in Man.

PMID- 29639239
TI  - A Few More Words on Centenarianism.

PMID- 29639241
TI  - Medical News.

PMID- 29639240
TI  - Meetings of Societies.

PMID- 29639242
TI  - Cases Illustrative of a Form of Asthenic Insanity.

PMID- 29639243
TI  - Cirrhosis of the Stomach.

PMID- 29639245
TI  - On the Surgical Applications of Electricity: Introductory to a Course of Lectures
      on Systematic Surgery.

PMID- 29639244
TI  - On the Physiology of the Circulation in Plants, in the Lower Animals, and in Man.

PMID- 29639246
TI  - Medical News.

PMID- 29639247
TI  - On a Curious Form of Injury to a Female Produced by a Goat.

PMID- 29639248
TI  - Introductory Address, Edinburgh Medical School.

PMID- 29639249
TI  - Meetings of Societies.

PMID- 29639250
TI  - Erratum.
AB  - [This corrects the article on p. 1123 in vol. 17.].

PMID- 29639251
TI  - Case of Traumatic Tetanus, Successfully Treated with Chloral and Bromide of
      Potassium.

PMID- 29639252
TI  - Medical News.

PMID- 29639253
TI  - Case of Sudden Death during an Operation, Due Either to Chloroform or to the
      Entrance of Air into the Veins.

PMID- 29639254
TI  - Some Remarks on the Pathology and Treatment of Acne.

PMID- 29639256
TI  - Case of Shoulder Presentation, with Rigid Os and Prolapse of Funis: Turning
      Impossible; Delivery Effected by Spondylotomy.

PMID- 29639255
TI  - Case of Gastrotomy.

PMID- 29639257
TI  - Correspondence.

PMID- 29639258
TI  - Meetings of Societies.

PMID- 29639259
TI  - Lecture I.-On the Connexion between the Chemical Properties and the Physiological
      Action of Active Substances.

PMID- 29639260
TI  - On the Physiology of the Circulation in Plants, in the Lower Animals, and in Man.

PMID- 29639262
TI  - Indigestion and Its Management.

PMID- 29639261
TI  - The Therapeutic Actions of Muriate of Lime.

PMID- 29639263
TI  - On the Erectile Action of the Blood-Pressure in Inspiration, and Its Important
      Agency in the Various Functions of Life.

PMID- 29639264
TI  - Information Regarding Medical Education and Examinations.

PMID- 29639265
TI  - Army Medical School.

PMID- 29639266
TI  - List of Hospitals, Dispensaries, Etc., in Connexion with the Medical Schools of
      Scotland.

PMID- 29639267
TI  - Medical News.

PMID- 29639269
TI  - Experiments in Epilepsy.

PMID- 29639268
TI  - Treatment of Pruritus Vulvae.

PMID- 29639270
TI  - Army Medical Department.

PMID- 29639272
TI  - Indian Medical Service.

PMID- 29639271
TI  - The Generative Expenditure of Man.

PMID- 29639273
TI  - The Suicidal Tendency as Manifested in Asthenic Insanity.

PMID- 29639274
TI  - A Simple Mode of Delivery in Shoulder Presentation, in Which Version Cannot Be
      Safely Effected.

PMID- 29639275
TI  - Address to the Edinburgh Medical Graduates, 1st August 1872.

PMID- 29639276
TI  - Remarks on Medical Study.

PMID- 29639278
TI  - Meetings of Societies.

PMID- 29639277
TI  - Action of Digitalis.

PMID- 29639280
TI  - Physiological Action of Tobacco-Smoke.

PMID- 29639279
TI  - On the Physiology of the Circulation in Plants, in the Lower Animals, and in Man.

PMID- 29639281
TI  - Navy Medical Department.

PMID- 29639282
TI  - Medical News.

PMID- 29639283
TI  - Extirpation of the Lower End of the Rectum.

PMID- 29639284
TI  - Valedictory Address to the Medico-Chirurgical Society of Edinburgh, Delivered on
      the Occasion of Retiring from the Chair of the Society, 7th January 1874.

PMID- 29639285
TI  - Children's Hospital Papers: Clinical Observations on Pneumonia.

PMID- 29639286
TI  - Case of Extensive Chronic Eczema of the Face and Extremities, of Seven Years'
      Standing, in a Child, and Complicated with Spasmodic Asthma, Cured by Pitch, Soft
      Soap, Zinc, and the Iodide of Potassium.

PMID- 29639287
TI  - Lister's Method of the Treatment of Wounds: Einige Worte zum Verstandniss der
      Lister'schen Methode der Wundbehandlung.

PMID- 29639288
TI  - Report of a Case of Intracranial Tumour; with Remarks.

PMID- 29639289
TI  - Penetrating Gunshot Wound of the Pelvis.

PMID- 29639290
TI  - Meetings of Societies.

PMID- 29639291
TI  - The Bromide Question.

PMID- 29639292
TI  - Animal Locomotion, or Walking, Swimming, and Flying.

PMID- 29639293
TI  - Post-Mortem.

PMID- 29639294
TI  - Experiments Confirming Dr Fergus's Views as to the Passage of Gases through Water
      Traps.

PMID- 29639295
TI  - Case of Arterio-Venous Aneurism of the Arch of the Aorta.

PMID- 29639296
TI  - A New Sign of Death.

PMID- 29639297
TI  - Report of, and Observations upon, a Case of Twins with Double Placenta Praevia
      (Partial), and Both Children Presenting Transversely-Abortion from Typhoid Fever
      in Previous Pregnancy.

PMID- 29639298
TI  - Contra-Indications of Operative Interference in Cases of Melanotic Tumour Derived
      from a Microscopic Examination of the Blood and of the Urine.

PMID- 29639299
TI  - Medical News.

PMID- 29639300
TI  - The Use of the Electro-Magnetic Current in Labour: Notes of Two Cases.

PMID- 29639301
TI  - Large Doses of the Bromide of Potassium in Epilepsy.

PMID- 29639302
TI  - Meetings of Societies.

PMID- 29639304
TI  - Case of Extirpation of the Kidney.

PMID- 29639303
TI  - On the Etiology of Variola.

PMID- 29639305
TI  - The Early Cases of a Typhus Outbreak.

PMID- 29639306
TI  - Report on Ophthalmology.

PMID- 29639307
TI  - Excision of the Anterior Tarsus and Base of the Metatarsus-A New Operation.

PMID- 29639308
TI  - Sudden Death from Embolism of the Pulmonary Artery, after Inflammation of
      Varicose Veins.

PMID- 29639310
TI  - The Natural History of Infectious Diseases.

PMID- 29639309
TI  - Valedictory Address to the Medico-Chirurgical Society of Edinburgh, Delivered on
      the Occasion of Retiring from the Chair of the Society, 7th January 1874.

PMID- 29639311
TI  - The Operation of Repositio Ciliorum for Trichiasis.

PMID- 29639312
TI  - Sulphate of Cinchonia.

PMID- 29639313
TI  - Aspiration in Retention.

PMID- 29639315
TI  - A Case of Cornu Humanum of External Ear.

PMID- 29639314
TI  - Medical News.

PMID- 29639316
TI  - Extirpation of Kidney.

PMID- 29639317
TI  - Children's Hospital Papers: Clinical Observations on Pneumonia.

PMID- 29639318
TI  - Physiological Papers: Observations on the Mechanism of the Ear.

PMID- 29639319
TI  - On Idiocy, Especially in Its Physical Aspects.

PMID- 29639320
TI  - Death from Inhalation of the Products of Combustion, in an Open Fireplace with a
      Chimney.

PMID- 29639321
TI  - On a Cause of Retention of Urine in Fibrous Tumour of the Uterus, with Cases.

PMID- 29639322
TI  - Amputation in Aged Subjects.

PMID- 29639323
TI  - The School of Physiology at Leipzig.

PMID- 29639324
TI  - Cases Illustrating Diseases of the Ear.

PMID- 29639325
TI  - Epidemic of Goitre in a Barrack.

PMID- 29639326
TI  - Meetings of Societies.

PMID- 29639327
TI  - Statistics of Gunshot Wounds of the Hip-Joint.

PMID- 29639328
TI  - Researches as to the Pathology of Perforating Disease of the Foot.

PMID- 29639329
TI  - Case of Siren-Like Malformed Foetus at Full Time, with a Well-Formed Penis on the
      Posterior Aspect of the Body.

PMID- 29639330
TI  - Carbazotate of Ammonia as a Substitute for Sulphate of Quinia.

PMID- 29639331
TI  - In Favour of a New Method of Healing Ulcers.

PMID- 29639332
TI  - Grafting the Skin of a White Man upon a Negro.

PMID- 29639333
TI  - Twin-Pregnancy after Ovariotomy.

PMID- 29639334
TI  - Three Cases of Pleural Effusion Treated Successfully by Pneumatic Aspiration.

PMID- 29639335
TI  - On the Extension and Increase of the Scientific Spirit in Medicine.

PMID- 29639336
TI  - Case of Cephalotripsy after Turning.

PMID- 29639337
TI  - Physiological Papers: On the Inhibitory or Restraining Action Which the
      Encephalon Exerts on the Reflex Centres of the Spinal Cord.

PMID- 29639338
TI  - Fracture of the Clavicle Treated by Placing the Arm behind the Back.

PMID- 29639339
TI  - Statistics of Births and Deaths.

PMID- 29639340
TI  - On Idiocy, Especially in Its Physical Aspects.

PMID- 29639341
TI  - Meetings of Societies.

PMID- 29639342
TI  - The Superior Value of Artificial Premature Labour and Turning, over the High
      Forceps Operation and Craniotomy, in Cases of Contracted Pelvis; with Cases.

PMID- 29639343
TI  - The Sewage Question; with Remarks and Experiments Showing the Inefficiency of Our
      Present System of Trapping.

PMID- 29639345
TI  - Inflammation of Ganglion Cells.

PMID- 29639344
TI  - Polypus of the Larynx-Removal by Section of the Thyroid Cartilage-Recovery.

PMID- 29639346
TI  - Medical News.

PMID- 29639347
TI  - Clinical Lectures on Diseases of the Heart.

PMID- 29639348
TI  - Medical News.

PMID- 29639350
TI  - Dissection of a Recent Case of Colles's Fracture of the Radius, with Remarks on
      the Pathology.

PMID- 29639349
TI  - Pelvimetry: A Method of Estimating the Conjugata Vera.

PMID- 29639351
TI  - Fork-Swallowers.

PMID- 29639352
TI  - Medical News.

PMID- 29639353
TI  - On the Sulphides of Potassium, Sodium, and Calcium.

PMID- 29639354
TI  - Valedictory Address to the Medico-Chirurgical Society of Edinburgh, Delivered on
      the Occasion of Retiring from the Chair of the Society, 7th January 1874.

PMID- 29639356
TI  - Syphilitic Membranoid Occlusion of the Rima Glottidis.

PMID- 29639355
TI  - Meetings of Societies.

PMID- 29639357
TI  - Report on Ophthalmology.

PMID- 29639358
TI  - Case of Infantile Convulsions Treated by Means of Bromide of Potassium.

PMID- 29639359
TI  - M. Charcot on Meniere's Disease, or Vertigo ab Aure Laesa.

PMID- 29639361
TI  - Valedictory Address to the Medico-Chirurgical Society of Edinburgh.

PMID- 29639360
TI  - Correspondence.

PMID- 29639362
TI  - Danger of Sharp-Pointed Foreign Bodies in the Bladder.

PMID- 29639364
TI  - Aspiration as a Means of Treating Cases of Urgent Retention of Urine.

PMID- 29639363
TI  - Double Spleen and Kidneys.

PMID- 29639365
TI  - Case of Madura Foot-Mycetoma.

PMID- 29639367
TI  - Meetings of Societies.

PMID- 29639368
TI  - On the Size of Aperture Necessary for the Passage of the Placenta and for the
      Passage of the Accoucheur's Hand.

PMID- 29639366
TI  - Albuminuria in Cases of Vascular Bronchocele and Exophthalmos.

PMID- 29639369
TI  - Complete Removal of the Larynx.

PMID- 29639370
TI  - Abortive Treatment of Boils.

PMID- 29639371
TI  - On Certain Organic Disorders and Defects of Memory.

PMID- 29639372
TI  - Action for the Fees of a Consultant in a Midwifery Case in France.

PMID- 29639373
TI  - Professor Mosler on the Introduction of Large Quantities of Fluid into the
      Intestinal Canal in the Treatment of Internal Diseases.

PMID- 29639374
TI  - Abstract of a Pamphlet on the Origin of Syphilis.

PMID- 29639375
TI  - Royal College of Physicians.

PMID- 29639376
TI  - Gunshot Wound of the Cerebellum-Absence of Special Symptoms.

PMID- 29639378
TI  - On the Origin of Cancer.

PMID- 29639377
TI  - Gastrotomy in Extra-Uterine Pregnancy.

PMID- 29639379
TI  - Hypodermic Injection of Ergotin in Internal Haemorrhages.

PMID- 29639380
TI  - Case of Renal Abscess with Contained Calculus, Successfully Relieved by
      Operation.

PMID- 29639382
TI  - Medical News.

PMID- 29639381
TI  - On the Physiology of the Circulation in Plants, in the Lower Animals, and in Man.

PMID- 29639383
TI  - Hypodermic Injection of Sulphate of Morphia in Autumnal Catarrh.

PMID- 29639384
TI  - Obstinate Recurrent Neuroma after Amputation; Cure by Electro-Puncture.

PMID- 29639385
TI  - Tenotomy of the Superior Rectus.

PMID- 29639387
TI  - Meetings of Societies.

PMID- 29639386
TI  - Galvano-Acupuncture for Aortic Aneurism.

PMID- 29639388
TI  - Puncture of the Bladder above the Pubes.

PMID- 29639390
TI  - The Cold-Bath Treatment in Acute Disease.

PMID- 29639389
TI  - On the Differential Stethoscope, and Its Value in the Diagnosis of Diseases of
      the Lungs and Heart.

PMID- 29639391
TI  - Medico-Topographical Report of the Station of Futtehgurh, N.W.P. India.

PMID- 29639392
TI  - Consumption in the Highlands and Islands to the West of Scotland, with Reference
      to the Immunity Claimed for These Districts While the People Remain at Home.

PMID- 29639393
TI  - Medical News.

PMID- 29639394
TI  - Case of Rare Tumour of the Lower Jaw Successfully Removed without Division of the
      Bone.

PMID- 29639395
TI  - Medical News.

PMID- 29639396
TI  - Case of Hypospadias with Cleft Scrotum, Believed a Female Till Fourteen Years of
      Age.

PMID- 29639397
TI  - Meetings of Societies.

PMID- 29639398
TI  - Medical News.

PMID- 29639399
TI  - Case of Elephantiasis of the Leg; Successful Amputation through the Elephantiasis
      Tissue.

PMID- 29639401
TI  - A Case of Dilatation of the Bile-Ducts, Followed by Abscess of the Liver.

PMID- 29639400
TI  - On the Physiology of the Circulation in Plants, in the Lower Animals, and in Man.

PMID- 29639403
TI  - Medical News.

PMID- 29639402
TI  - Note of a Proof of the Free Intercommunication, near the Chorionic Surface,
      between Different Parts of the System of Maternal Cells or Blood-Caverns of the
      Placenta, in the Same, and in Different Cotyledons.

PMID- 29639404
TI  - On an Apparatus for Maintaining Artificial Respiration in Physiological
      Experiments.

PMID- 29639406
TI  - Carbonate of Ammonia in Uraemia.

PMID- 29639405
TI  - Acute Rheumatism in Private Practice.

PMID- 29639407
TI  - Cases Observed in the Royal Edinburgh Hospital for Sick Children; with
      Commentaries, Clinical and Pathological.

PMID- 29639408
TI  - Note of a Case of Rare Inguinal Swelling.

PMID- 29639409
TI  - The Connexion between Pulmonary Haemorrhage and Phthisis.

PMID- 29639410
TI  - Some Remarks on Insanity.

PMID- 29639411
TI  - Medical News.

PMID- 29639413
TI  - On the Antiseptic Plan of Treatment. Reports of a Few Cases.

PMID- 29639412
TI  - On the Effects of Lightning.

PMID- 29639414
TI  - On the Physiology of the Circulation in Plants, in the Lower Animals, and in Man.

PMID- 29639416
TI  - Meetings of Societies.

PMID- 29639415
TI  - On a Case of Rupture of the Axillary Artery in an Attempt to Reduce a Dislocation
      of the Shoulder.

PMID- 29639417
TI  - Nitrate of Land in the Treatment of Onychia Maligna.

PMID- 29639418
TI  - Case of Aneurism of the Arch of the Aorta, Treated Successfully by Iodide of
      Potassium.

PMID- 29639419
TI  - On the Changes Undergone by the Cervix Uteri during Labour.

PMID- 29639420
TI  - Polypus of Posterior Nares Destroyed by Electricity.

PMID- 29639422
TI  - Mode of Increasing or Assisting the Growth of Bones.

PMID- 29639421
TI  - Latent Gonorrhaea in the Female Sex, with Special Relation to the Puerperal
      State.

PMID- 29639423
TI  - On a Rare Cause of Mistake in Testing Urine for Albumen by the Ordinary
      Processes.

PMID- 29639424
TI  - Calabar Bean in Constipation.

PMID- 29639425
TI  - Medical News.

PMID- 29639427
TI  - Medical News.

PMID- 29639426
TI  - Clement's Solution of Arsenic.

PMID- 29639428
TI  - New Method of Treating Functional Dyspepsia, Anaemia, and Chlorosis.

PMID- 29639430
TI  - Notes of a Few Surgical Cases Treated in the Country.

PMID- 29639429
TI  - On the Causes of the Predisposition to Phthisis among the Natives of the Hebrides
      and West Highlands, and the Suitability of the Country as a Resort for Invalids.

PMID- 29639432
TI  - Hunting out Cholera.

PMID- 29639431
TI  - Propylamine.

PMID- 29639434
TI  - The Thermometer as a Means of Diagnosis in Cases of Uraemia.

PMID- 29639433
TI  - A Few Words on the Means Necessary to Be Taken for Preventing the Spread of
      Zymotic Disease.

PMID- 29639435
TI  - Brief Retrospect of the Recent History of Lithotomy, with an Account of a New
      Method of Performing the Operation.

PMID- 29639436
TI  - Chloral Hydrate to Restore Blood-Corpuscles.

PMID- 29639437
TI  - Hyoscyamia.

PMID- 29639438
TI  - Meetings of Societies.

PMID- 29639440
TI  - Some Remarks on Insanity.

PMID- 29639439
TI  - A Remedy for Haemoptysis.

PMID- 29639441
TI  - Medical News.

PMID- 29639442
TI  - Meetings of Societies.

PMID- 29639443
TI  - Acne and Its Treatment.

PMID- 29639444
TI  - On Excision of the Extremity of the Humerus as a Remedial Measure in Cases of
      Anchylosis of the Elbow-Joint Resulting from Injury.

PMID- 29639447
TI  - Notes on Two Cases of Accidental Poisoning.

PMID- 29639446
TI  - Case of Pre-Parturient Insanity; Suicide of Patient.

PMID- 29639445
TI  - On the Physiology of the Circulation in Plants, in the Lower Animals, and in Man.

PMID- 29639448
TI  - Dr Handyside's Additional Remarks on Dr Graham's Case of Hypospadias with Cleft
      Scrotum, Etc.

PMID- 29639449
TI  - On the Treatment of Haemorrhoids in Pregnant and Puerperal Women.

PMID- 29639450
TI  - On the Treatment of Scabies in Children.

PMID- 29639451
TI  - Medico-Topographical Report of the Station of Futtehgurh, N.W.P. India.

PMID- 29639452
TI  - Case of Pregnancy and Labour Complicated with Diabetes Mellitus.

PMID- 29639453
TI  - The Sensory and Mental Deficiencies of Idiots.

PMID- 29639454
TI  - Tracheotomy for Croup in Child of Ten Monthly-Cure.

PMID- 29639455
TI  - On the Physiology of the Circulation in Plants, in the Lower Animals, and in Man.

PMID- 29639456
TI  - Note of an Unusual Form of Haematocele.

PMID- 29639458
TI  - Meetings of Societies.

PMID- 29639457
TI  - On Infantile Enteralgia.

PMID- 29639459
TI  - Jolly on the Dangers of Chloral Hydrate.

PMID- 29639460
TI  - Correspondence.

PMID- 29639461
TI  - The Efficacy and Mode of Employing Collodion in Erysipelas.

PMID- 29639463
TI  - Tannin Packing in Prolapsus Uteri, Etc.

PMID- 29639462
TI  - On the Necessary Conditions of Sensations, as Illustrated by the Sense of
      Hearing.

PMID- 29639464
TI  - Medical News.

PMID- 29639465
TI  - Medical News.

PMID- 29639466
TI  - Fractures of the Patella in Children.

PMID- 29639467
TI  - Benign Giant-Cell Tumours of Joints.

PMID- 29639468
TI  - Tracheocele.

PMID- 29639469
TI  - Some Points in Regard to the Genesis of Mesoblastic Tumours.

PMID- 29639471
TI  - Arterial Perforations by Exostoses.

PMID- 29639470
TI  - A Neolithic War Wound.

PMID- 29639472
TI  - Trauma and Benign Tumours.

PMID- 29639473
TI  - Some Observations on the Treatment of Mental Diseases.

PMID- 29639474
TI  - Ptosis and Periarterial Sympathectomy.

PMID- 29639475
TI  - Traumatic Thyreoid Haematocele.

PMID- 29639476
TI  - The Mechanism of Spinal Anaesthesia in Intestinal Ileus.

PMID- 29639477
TI  - A Departure from the Usual Methods in Treating Obesity.

PMID- 29639478
TI  - Aneurysm and Popliteal Exostosis.

PMID- 29639479
TI  - Lithiasis in Horseshoe Kidney.

PMID- 29639480
TI  - Chemical Methods Applied to the Determination of Sex. A Review of Recent Work.

PMID- 29639481
TI  - An Edinburgh Medical Family.

PMID- 29639482
TI  - Schistosomiasis of the Conjunctiva.

PMID- 29639483
TI  - Tabetic Arthropathy (Charcot's Arthritis) of the Knee of a Young Girl.

PMID- 29639485
TI  - Acute Septic Osteitis of the Calcaneum.

PMID- 29639484
TI  - Haematomata of the Anterior Abdominal Wall.

PMID- 29639487
TI  - Spontaneous Cure of Cancer.

PMID- 29639486
TI  - Melanotic Tumours.

PMID- 29639488
TI  - Unilateral Furring of the Tongue.

PMID- 29639490
TI  - Narcolepsy.

PMID- 29639489
TI  - The Prophylaxis of Spinal Anaesthesia Sequelae.

PMID- 29639492
TI  - Primary Osteomyelitis of the Ribs.

PMID- 29639491
TI  - Therapeutic Uses of Carbonic Acid.

PMID- 29639493
TI  - Local Accidents Following Intramuscular Therapy.

PMID- 29639494
TI  - Volvulus of the Healthy Uterine Tube.

PMID- 29639495
TI  - The Inter-Relations of the Thyroid, Adrenals and Nervous System.

PMID- 29639497
TI  - Fixation of Fractures by Operation.

PMID- 29639496
TI  - Cutaneous Metastases in Lingual Cancer.

PMID- 29639499
TI  - Review of the Comparative Values of Surgery, Deep X-Ray Therapy and Radium in
      Uterine Disease.

PMID- 29639498
TI  - A Scrotal Kidney.

PMID- 29639500
TI  - The Skull in Osteosclerotic Anaemia.

PMID- 29639503
TI  - Periarterial Sympathectomy in Perforating Ulcer.

PMID- 29639502
TI  - Familial Cystinuria.

PMID- 29639501
TI  - The Bronchoscopic Diagnosis and Treatment of Bronchiectasis and Other Chronic Non
      Tubercular Diseases of the Chest.

PMID- 29639504
TI  - Notes.

PMID- 29639505
TI  - Volvulus of the Testicular Appendix.

PMID- 29639507
TI  - Acute Septic Vertebral Osteomyelitis.

PMID- 29639506
TI  - The Treatment of Lobar Pneumonia, with Special Reference to the Use of Nuclein
      and of Vaccines.

PMID- 29639508
TI  - Subacute Infarction of the Testis and Torsion of the Cord.

PMID- 29639509
TI  - Wounds of the Cavernous Sinus.

PMID- 29639510
TI  - Acute Pneumonia in the Recent Influenza Epidemic: A Clinical and Bacteriological
      Study in a Series of Fifty Cases.

PMID- 29639511
TI  - Post-Encephalitic Delinquency.

PMID- 29639512
TI  - The Care and Prevention of Rheumatism in Childhood.

PMID- 29639513
TI  - Clinical Arterioscopy and Arteriography in the Living Subject.

PMID- 29639514
TI  - Obstetrical Symphysiotomy.

PMID- 29639515
TI  - Cervical Air Cyst from the Larynx.

PMID- 29639516
TI  - Clinical Meeting.

PMID- 29639518
TI  - Medical Education in Scotland.

PMID- 29639517
TI  - Egypt and Medicine: Retrospective and Prospective.

PMID- 29639519
TI  - Mental Inefficiency in School Children.

PMID- 29639521
TI  - Post-Operative Pulmonary Embolism.

PMID- 29639520
TI  - The Surgical Aspects of Chronic Pulmonary Suppuration.

PMID- 29639524
TI  - Some Observations on the Clinical and Bacteriological Aspects of Suppuration of
      the Lung.

PMID- 29639523
TI  - Intrahepatic Cholelithiasis.

PMID- 29639522
TI  - Sacrococcygeal Fistulae.

PMID- 29639525
TI  - The Dangers of Intra-Uterine Injections for Radiography.

PMID- 29639526
TI  - Notes.

PMID- 29639528
TI  - Traumatic Rupture of Quadriceps Femoris.

PMID- 29639527
TI  - Immediate Traumatic Blindness.

PMID- 29639529
TI  - Pancreatic Cysts.

PMID- 29639530
TI  - Rupture of Abdominal Cicatrices.

PMID- 29639532
TI  - Pes Cavus: A Clinical Study with Special Reference to Its Etiology.

PMID- 29639531
TI  - Bee's Sting of the Eyeball.

PMID- 29639534
TI  - Congenital Scoliosis and Dolichocephaly as Correlated Developmental Defects.

PMID- 29639533
TI  - Illustration of Tumours.

PMID- 29639536
TI  - Volvulus of the Appendix.

PMID- 29639535
TI  - Sudden Death and Suprarenal Disease.

PMID- 29639537
TI  - Notes.

PMID- 29639538
TI  - Mixed Carcinoma of the Kidney.

PMID- 29639539
TI  - Accidental Uterine Perforation.

PMID- 29639541
TI  - Cyst of the Mesosigmoid.

PMID- 29639540
TI  - The Tolerance of Intact Mucosa.

PMID- 29639544
TI  - Surgery.

PMID- 29639542
TI  - Ureteral Prolapse.

PMID- 29639543
TI  - Post-Traumatic Suture of the Radial Nerve.

PMID- 29639546
TI  - Case of Epilepsy Connected with Vesical Calculus, Cured by Lithotomy.

PMID- 29639545
TI  - Reports of Cases of Extractions by Linear Flap.

PMID- 29639547
TI  - Thermometrical Observations.

PMID- 29639548
TI  - General Council of Medical Education and Registration.

PMID- 29639549
TI  - Cancer Curing: Letter to the Editor.

PMID- 29639550
TI  - Medicine.

PMID- 29639551
TI  - Medical News.

PMID- 29639552
TI  - The Hepatic System in Animals an Apparatus for Preventing the Animal Cells from
      Being Coated by Cellulose, and Fixed.

PMID- 29639553
TI  - Sketch of the Early History of Anatomy: An Address Delivered to the Hunterian
      Medical Society, in the University of Edinburgh, at the Commencement of the
      Session 1867-68.

PMID- 29639554
TI  - Meetings of Societies.

PMID- 29639555
TI  - Aix-La-Chapelle: Letter from an Edinburgh Doctor to a Professional Friend at
      Home.

PMID- 29639556
TI  - On Haemoptysis, Especially When Fatal, in Its Anatomical and Clinical Aspects.

PMID- 29639557
TI  - On the Use of Croton Oil as a Counter-Irritant in Head Affections.

PMID- 29639558
TI  - A Brief Review and Estimate of the Professional Writings of Benjamin Bell,
      F.R.C.S.E., F.R.S.E., Author of "A System of Surgery," and Other Works.

PMID- 29639559
TI  - Case of Ovarian Cystic Tumour.

PMID- 29639561
TI  - Fatal Case of Intussusception, Being the Sequel of "A Case of Intussusception
      Terminating in Sloughing and Discharge of the Intussuscepted Portion of
      Intestine, and Recovery".

PMID- 29639560
TI  - Medical News.

PMID- 29639562
TI  - Case of Arm Presentation Terminating by Spontaneous Evolution.

PMID- 29639563
TI  - Report on Ophthalmology.

PMID- 29639564
TI  - General Council of Medical Education and Registration.

PMID- 29639566
TI  - Surgery.

PMID- 29639565
TI  - On the Therapeutical Action of Medicines in Dilated Conditions of the
      Bloodvessels-Digitalis.

PMID- 29639567
TI  - Address to the Edinburgh Medical Graduates, August 1, 1868.

PMID- 29639568
TI  - Important to the Medical Profession.

PMID- 29639570
TI  - Medical News.

PMID- 29639569
TI  - Two Cases of Hydrophobia.

PMID- 29639571
TI  - Graduation in Medicine at the University of Edinburgh.

PMID- 29639572
TI  - Medicine.

PMID- 29639573
TI  - On a New Lesion Observed in the Brain of an Insane Person.

PMID- 29639575
TI  - Meetings of Societies.

PMID- 29639574
TI  - Case of Infantile Convulsions.

PMID- 29639576
TI  - On a Case of Gliomatous Tumour of the Brain.

PMID- 29639577
TI  - Medical News.

PMID- 29639578
TI  - On Haemoptysis, Especially When Fatal, in Its Anatomical and Clinical Aspects.

PMID- 29639579
TI  - Medical News.

PMID- 29639580
TI  - Pathology.

PMID- 29639581
TI  - A Somewhat Peculiar Case of Fever.

PMID- 29639582
TI  - Cases of Ovariotomy.

PMID- 29639584
TI  - Materia Medica and Therapeutics.

PMID- 29639583
TI  - Midwifery and Diseases of Women.

PMID- 29639585
TI  - On the Construction of the Cephalotribe.

PMID- 29639587
TI  - Meetings of Societies.

PMID- 29639586
TI  - On the Action of the Cobra Poison.

PMID- 29639589
TI  - British Association for the Advancement of Science.

PMID- 29639588
TI  - A Case of Meningo-Cerebritis, Caused Probably by Exposure to the Sun.

PMID- 29639590
TI  - Reasons for Preferring Lithotrity to Lithotomy in Operating for Stone in the
      Adult Male, with Cases.

PMID- 29639591
TI  - Naval Medical Department.

PMID- 29639592
TI  - Meetings of Societies.

PMID- 29639593
TI  - Reports of Cases of Extractions by Linear Flap.

PMID- 29639595
TI  - Surgery.

PMID- 29639594
TI  - On the Treatment of Aneurism by Iodide of Potassium.

PMID- 29639596
TI  - Scottish Universities Union.

PMID- 29639597
TI  - Case of Labour Impeded by a Strong Septum of the Vagina.

PMID- 29639598
TI  - Case of Plastic Bronchitis, with "Quasi" Diphtheritic Exudation.

PMID- 29639599
TI  - On the Early History of Syphilis in China.

PMID- 29639600
TI  - On Typhomania.

PMID- 29639601
TI  - The Indian Medical Service.

PMID- 29639602
TI  - Three Cases of Puerperal Convulsions Coming on at the Commencement of Labour.

PMID- 29639604
TI  - Midwifery.

PMID- 29639603
TI  - Report on the Hurdwar Cholera of 1867.

PMID- 29639605
TI  - Navy Medical Department.

PMID- 29639606
TI  - List of Hospitals, Dispensaries, Etc., in Connexion with the Medical Schools of
      Scotland.

PMID- 29639607
TI  - Army Medical School.

PMID- 29639608
TI  - Remarks on Medical Study.

PMID- 29639609
TI  - Army Medical Department.

PMID- 29639610
TI  - Medico-Chirurgical Society of Glasgow.

PMID- 29639611
TI  - Inhalation of Bichloride of Methylene.

PMID- 29639612
TI  - Medical News.

PMID- 29639613
TI  - Indian Medical Service.

PMID- 29639614
TI  - Information Regarding Medical Education and Examinations.

PMID- 29639615
TI  - Cases of Ovariotomy.

PMID- 29639617
TI  - General Council of Medical Education and Registration.

PMID- 29639616
TI  - Observations on the Physiology and Pathology of Hemi-Chorea.

PMID- 29639618
TI  - Surgery.

PMID- 29639619
TI  - Case of Removal of a Large Piece of Sealing-Wax from the Bladder of the Male by
      Lithotrity.

PMID- 29639620
TI  - Case of Tetanus, Treated by Bromide of Potassium.

PMID- 29639621
TI  - Cases Illustrative of the Antiseptic Use of Carbolic Acid.

PMID- 29639622
TI  - Meetings of Societies.

PMID- 29639623
TI  - On the Action of the Cobra Poison.

PMID- 29639624
TI  - Cases of Ovariotomy.

PMID- 29639626
TI  - On the Treatment of Aneurism by Compression, with Two Cases of Its Successful
      Application.

PMID- 29639627
TI  - Medical News.

PMID- 29639625
TI  - Case of Traumatic Tetanus: Recovery under the Use of the Calabar Bean.

PMID- 29639629
TI  - On Cholera at Shanghai.

PMID- 29639628
TI  - The Treatment of Congenital Talipes Varus in the Infant.

PMID- 29639630
TI  - On an Interesting Series of Eye-Symptoms in a Case of Spinal Disease, with
      Remarks on the Action of Belladonna on the Iris, Etc.

PMID- 29639631
TI  - Thermometrical Observations.

PMID- 29639632
TI  - Pathology and Treatment of Uterine Displacements.

PMID- 29639633
TI  - Meetings of Societies.

PMID- 29639635
TI  - Medical News.

PMID- 29639634
TI  - Case of Heart Disease; Partial Fibroid Degeneration, the Result of Myocarditis.

PMID- 29639636
TI  - Medicine.

PMID- 29639638
TI  - Surgery.

PMID- 29639637
TI  - Medical News.

PMID- 29639640
TI  - Meetings of Societies.

PMID- 29639639
TI  - Traumatic Cerebral Abscess.

PMID- 29639641
TI  - Case of Enlarged Spleen Complicated with Ascites, Both Depending upon Varicose
      Dilatation and Thrombosis of the Portal Vein.

PMID- 29639642
TI  - Case of Congenital Malformation of the OEsophagus.

PMID- 29639643
TI  - On the Variation and Vanishing of Cardiac Organic Valvular Murmurs.

PMID- 29639644
TI  - Acupuncture in a Case of Cancer.

PMID- 29639645
TI  - Case of Rupture of the Uterus during Parturition.

PMID- 29639646
TI  - Spasm of the Group of Muscles Supplied by the Musculo-Spiral Nerve.

PMID- 29639647
TI  - The Arrestment of Haemorrhage after Operations.

PMID- 29639648
TI  - Naval Medical Department.

PMID- 29639650
TI  - Midwifery.

PMID- 29639649
TI  - Case of Craniotomy.

PMID- 29639651
TI  - Report on Ophthalmology.

PMID- 29639652
TI  - The Increased Length of the Cervix Uteri after Labour, and in Other Conditions.

PMID- 29639653
TI  - Account of a Case of Gastric Ulcer Terminating by Perforation, Which Ran an
      Unusually Rapid Course.

PMID- 29639654
TI  - Meetings of Societies.

PMID- 29639655
TI  - Remarks on Retroversion of the Gravid Uterus.

PMID- 29639656
TI  - Monthly Retrospect of Gynaecology.

PMID- 29639657
TI  - Meetings of Societies.

PMID- 29639658
TI  - Periscope of Otology.

PMID- 29639659
TI  - Minto House Medical School, Edinburgh.

PMID- 29639660
TI  - Temperature and Pulse Chart.

PMID- 29639662
TI  - On Some of the Surgical Uses of Elastic Compression.

PMID- 29639661
TI  - Tartrate of Morphia as an Agent for Hypodermic Injection.

PMID- 29639664
TI  - Occasional Periscope of Dermatology.

PMID- 29639663
TI  - The Eucalyptus.

PMID- 29639665
TI  - Remarks on the Use of Solution of Perchloride of Iron as a Styptic and Caustic in
      Gynecological Practice.

PMID- 29639666
TI  - Case in Which a Strangulated Hernia, Reduced "en bloc," Was Relieved by a Median
      Abdominal Incision.

PMID- 29639667
TI  - Somnambulism.

PMID- 29639668
TI  - Monthly Retrospect of Obstetrics and Gynaecology.

PMID- 29639670
TI  - The Eucalyptus.

PMID- 29639669
TI  - Periscope of Otology.

PMID- 29639671
TI  - Meetings of Societies.

PMID- 29639672
TI  - Case of Guinea Worm.

PMID- 29639673
TI  - The Premurmuric Stage of Aortic Valvulitis.

PMID- 29639674
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29639675
TI  - Cases of Intra-Cranial Tumour.

PMID- 29639676
TI  - Observations on Some Points in Dextral Valvular Disease of the Heart, Being a
      Graduation Thesis.

PMID- 29639677
TI  - The Histology of Psoriasis.

PMID- 29639678
TI  - Aberdeen University-Appointments to Vacant Chairs.

PMID- 29639680
TI  - Royal Medical Society-New Office-Bearers.

PMID- 29639679
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29639682
TI  - Meetings of Societies.

PMID- 29639681
TI  - On Croup: Its Nature and Treatment.

PMID- 29639683
TI  - Gleanings from a Continental Holiday-The Inaugural Address at the First Meeting
      of the Royal Medical Society of Edinburgh, for the Session 1878-79.

PMID- 29639684
TI  - The Post-Mortem Appearances in a Case of Chronic Insanity; Hydrocephalus; Absence
      of Corpus Callosum.

PMID- 29639685
TI  - Notes of a Case of Successive Aneurisms.

PMID- 29639686
TI  - Remarks on the Condition of the Cervix Uteri during the Latter Months of
      Pregnancy, with Translation of a Paper by P. Muller of Berne on That Subject.

PMID- 29639687
TI  - Periscope of Otology.

PMID- 29639688
TI  - New Italian Medical Journal.

PMID- 29639689
TI  - Cases of Intra-Cranial Tumour.

PMID- 29639690
TI  - On Dystocia with Dorsal Displacement of the Arm.

PMID- 29639691
TI  - Dr Politzer's Text-Book of Aural Surgery.

PMID- 29639692
TI  - On the Influence of Head-Movements on Audition.

PMID- 29639693
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29639695
TI  - A Case of Aphasia.

PMID- 29639694
TI  - On the Therapeutic Value of Hydrocyanic Acid in Arresting the Night Cough of
      Children after Failure with the Bromides.

PMID- 29639696
TI  - Opening of the New Hertford British Hospital, Paris.

PMID- 29639697
TI  - Meetings of Societies.

PMID- 29639698
TI  - Case of Milk-Like Urine.

PMID- 29639700
TI  - The Late William Howitt.

PMID- 29639699
TI  - Cases Illustrating the Management of Tedious Labours.

PMID- 29639701
TI  - Eucalyptus Vegetation.

PMID- 29639704
TI  - Aural Periscope.

PMID- 29639703
TI  - Pain as a Symptom of Fracture.

PMID- 29639702
TI  - On the Adenoid Tumours of the Naso-Pharynx, and Their Influence on the Hearing,
      Breathing, and Phonation, and on Their Treatment.

PMID- 29639705
TI  - Suspension as an Aid to Surgical Demonstrations and Practice.

PMID- 29639706
TI  - On the Head-Flexion in Labour.

PMID- 29639707
TI  - Large Tumour Growing from the Clavicle.

PMID- 29639708
TI  - Periscope of Otology.

PMID- 29639709
TI  - Case of Poisoning from Fusel Oil and Aconite.

PMID- 29639711
TI  - Clinical Remarks on Gleet: Its Causes and Treatment.

PMID- 29639710
TI  - A Study of Two Mesial Vertical Sections of the Female Pelvis in Relation to the
      Normal Support of the Uterus and Prolapsus Uteri.

PMID- 29639712
TI  - Meetings of Societies.

PMID- 29639713
TI  - On the Adenoid Tumours of the Naso-Pharynx, and Their Influence on the Hearing,
      Breathing, and Phonation, and on Their Treatment.

PMID- 29639714
TI  - Concerning the Operation of John Hunter in Certain Cases of Impassable Stricture.

PMID- 29639715
TI  - A Description of Tarnier's Forceps.

PMID- 29639716
TI  - The Treatment of Knock-Knee.

PMID- 29639717
TI  - Correspondence.

PMID- 29639718
TI  - Occasional Periscope of Dermatology.

PMID- 29639719
TI  - Note of a Case of Spasmodic Contraction of the Lower Uterine Segment during the
      First Stage of Labour.

PMID- 29639720
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29639721
TI  - On a New Form of Section-Knife Especially Adapted to the Cutting of Large
      Sections.

PMID- 29639722
TI  - Membranous Croup and Diphtheria.

PMID- 29639723
TI  - Observations on the Pathology of the Biliary Passages and Their Clinical Bearing.

PMID- 29639725
TI  - A Case of Unilateral Hypertrophy.

PMID- 29639724
TI  - Resection of Superior Cervical Sympathetic Ganglia for Exophthalmic Goitre.

PMID- 29639726
TI  - Late Arthritis after Enteric Fever.

PMID- 29639728
TI  - A Case of Retropharyngeal (? Tonsillar) Myxosarcoma Observed during a Period of
      Twenty-Two Years.

PMID- 29639727
TI  - Ossifying Spondylitis.

PMID- 29639729
TI  - An Investigation of a Case of Rat-Bite Fever: Clinical Observations.
      Bacteriological Investigation.

PMID- 29639730
TI  - Syphilitic Broncho-Pneumonia.

PMID- 29639731
TI  - Enteric Pneumatosis.

PMID- 29639732
TI  - Localised Saponification of Fat.

PMID- 29639734
TI  - Multiple Myelomata.

PMID- 29639733
TI  - Pneumococcal Peritonitis.

PMID- 29639735
TI  - The Disciples of Boerhaave in Edinburgh.

PMID- 29639736
TI  - Retroperitoneal Cysts: With Reports of Two Cases.

PMID- 29639737
TI  - Wounds of the Spinal Theca.

PMID- 29639739
TI  - The Strawberry Gall-Bladder.

PMID- 29639738
TI  - Intersigmoid Hernia.

PMID- 29639740
TI  - The Earlier Recognition of Cancer.

PMID- 29639742
TI  - Medical Education in Scotland.

PMID- 29639741
TI  - The Failing Heart. The George Alexander Gibson Memorial Lecture.

PMID- 29639744
TI  - On the Diagnosis of Pericardial Effusion.

PMID- 29639745
TI  - Analytical Note: Allisatin-Femergin.

PMID- 29639743
TI  - Thyroxine: Recent Research.

PMID- 29639746
TI  - Notes.

PMID- 29639747
TI  - Syringomyelia with Cavities in Posterior Nerve Roots.

PMID- 29639748
TI  - Scarlatina, Diphtheria and Measles, Their Relations and Inter-Relations from the
      Medico-Sociological Standpoint.

PMID- 29639749
TI  - Ectopic Endometrial Tumours.

PMID- 29639750
TI  - The Re-Expansion of the Lung in Empyema, with Notes Regarding the Mechanical
      Effects of Carbon Dioxide Inhalation.

PMID- 29639751
TI  - Pruritis Ani: Treatment by Alcohol Injection.

PMID- 29639753
TI  - Analytical Note: Vitalia Meat Juice.

PMID- 29639752
TI  - On Symmetrical Thinness of the Parietal Bones.

PMID- 29639755
TI  - Ocular Phenomena Associated with Temporal Lobe Tumours.

PMID- 29639754
TI  - Leucocytic Changes after the Injection of Peptone, with Particular Reference to
      the Arneth Count.

PMID- 29639756
TI  - Paroxysmal Tachycardia.

PMID- 29639757
TI  - Osteitis Fibrosa.

PMID- 29639758
TI  - Varicose Ulcers.

PMID- 29639759
TI  - Cleft-Sternum and Ectopia Cordis.

PMID- 29639761
TI  - Treatment of Oxyuriasis.

PMID- 29639760
TI  - Artificial Immunity against Tuberculosis.

PMID- 29639762
TI  - Notes.

PMID- 29639763
TI  - Cranial Metastasis of Hypernephroma.

PMID- 29639765
TI  - Coronary Arterio-Sclerosis.

PMID- 29639764
TI  - Scrofula and Tubercle: With Reference to Ancient and Modern Doctrines of Abnormal
      Constitution in Tuberculosis.

PMID- 29639766
TI  - An Anomaly of the Bile Ducts.

PMID- 29639768
TI  - Traumatic Penile Displacement of the Testis.

PMID- 29639769
TI  - Discussion on Rheumatoid Arthritis.

PMID- 29639767
TI  - The Failing Heart. The George Alexander Gibson Memorial Lecture.

PMID- 29639770
TI  - Marriage of near Kin in Royalty.

PMID- 29639771
TI  - Cranial Pneumatocele.

PMID- 29639772
TI  - Leukoplakia Buccalis.

PMID- 29639773
TI  - Malignant Adenoma of the Sigmoid.

PMID- 29639774
TI  - Note on a Case of Abnormal Intestinal Rotation.

PMID- 29639775
TI  - Notes.

PMID- 29639776
TI  - The Suprarenals in Relation to Arteritis Obliterans Juvenilis.

PMID- 29639777
TI  - Acute Capillary Bronchitis Accompanying Pregnancy.

PMID- 29639779
TI  - New Views on the Thyroid.

PMID- 29639778
TI  - The Treatment of Scarlet Fever with Specific Antitoxic Serum.

PMID- 29639780
TI  - Parasitic Infection of the Urinary Tract: Report of a Case of Infection of the
      Urinary Tract by Acari, Together with an Analysis of Previously Reported Cases.

PMID- 29639781
TI  - Disease of the Fourth Ventricle of the Brain, with Glycosuria; Paralysis of the
      Fifth and Seventh Cranial Nerves on the Left Side; Paralysis of the Glosso
      Pharyngeal and Ultimately Pneumogastric Nerves; Disease of the Right Optic
      Thalamus and Gyral Softening with Partial Parlaysis of Sensation and Motion in
      the Left Arm and Leg, Etc.; Death; Necropsy.

PMID- 29639782
TI  - Occlusion of the Vagina.

PMID- 29639783
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29639784
TI  - Report of One Hundred Cases of Diseases of the Ear.

PMID- 29639786
TI  - Valedictory Address to the Medico-Chirurgical Society of Edinburgh, on Retiring
      from the Presidency.

PMID- 29639785
TI  - Terebene, as a Dressing for Wounds.

PMID- 29639787
TI  - Notes on Two Cases of Stricture of the OEsophagus.

PMID- 29639788
TI  - Meetings of Societies.

PMID- 29639790
TI  - List of Successful Army Medical Candidates.

PMID- 29639789
TI  - Correspondence.

PMID- 29639791
TI  - List of Successful Indian Medical Candidates.

PMID- 29639792
TI  - On the Treatment of Anomalies in the Spanning of the Drumhead.

PMID- 29639793
TI  - Clinical Notes on Some of the Eccentricities of Enteric Fever.

PMID- 29639794
TI  - The Dull Wire Curette in Gynecological Practice.

PMID- 29639796
TI  - Meetings of Societies.

PMID- 29639795
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29639797
TI  - On Retention of Urine in the Female.

PMID- 29639798
TI  - Cases of Aneurism of the Aorta Treated by the Iodide of Potassium.

PMID- 29639800
TI  - The Sewage Question.

PMID- 29639799
TI  - On the Rhythm of Auricular Impulses.

PMID- 29639801
TI  - On the Essential Pathology of Puerperal Eclampsia.

PMID- 29639802
TI  - Extraordinary Tolerance of a Poisonous Dose of Chloral Hydrate.

PMID- 29639803
TI  - A Very Extensively Diffused Case of Lupus Erythematosus.

PMID- 29639804
TI  - Notes of a Case of Extroversion of the Bladder and Epispadias.

PMID- 29639805
TI  - Abdominal Aorta Nearly Severed by a Bullet-Life Remaining at Least an Hour and
      Ten Minutes.

PMID- 29639806
TI  - Placenta Praevia, or Unavoidable Haemorrhage.

PMID- 29639807
TI  - Hydrophobia and Rabies.

PMID- 29639808
TI  - Medical Students of Paris.

PMID- 29639809
TI  - Meetings of Societies.

PMID- 29639810
TI  - On the Diagnosis of Anomalies in the Conducting-Apparatus of the Ear.

PMID- 29639812
TI  - Professor J. Bell Pettigrew.

PMID- 29639811
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29639813
TI  - Royal Medical Society.

PMID- 29639814
TI  - On Third Stage of Labour; Its Management: With Remarks on Position, Diet, Etc.,
      after Delivery.

PMID- 29639815
TI  - Practical Observations on Some of the More Common Diseases of Early Life.

PMID- 29639816
TI  - Mader.

PMID- 29639817
TI  - Note on the Antiseptic Dressing of Wounds.

PMID- 29639818
TI  - The Treatment of Fibroid Tumours of the Uterus: An Address at the Opening of the
      37th Session of the Edinburgh Obstetrical Society.

PMID- 29639819
TI  - Lecture Delivered at the Opening of Anderson College.

PMID- 29639820
TI  - The Course of Diphtheria in Two Brothers Almost Simultaneously Stricken-A
      Clinical Study.

PMID- 29639821
TI  - On Two Heart Cases Which Presented a Rare Form of Irregularity.

PMID- 29639822
TI  - The Warren Prize.

PMID- 29639823
TI  - Note on Some of the Therapeutic Virtues of the Eucalyptus Globulus.

PMID- 29639824
TI  - Dr Menzel of Trieste.

PMID- 29639825
TI  - On the Richness of the Red Globules in Hemoglobine.

PMID- 29639827
TI  - Doctors' Fees.

PMID- 29639826
TI  - Thoughts and Suggestions Concerning the Education of Deaf Children.

PMID- 29639828
TI  - Case of Injury of the Brain, Presenting Certain Anomalous Symptoms.

PMID- 29639829
TI  - Some Conditions Which Simulate Organic Disease of the Heart.

PMID- 29639830
TI  - Quinine a Physiological Antidote to the Malarial Poison.

PMID- 29639831
TI  - Mo.

PMID- 29639832
TI  - The Protection Bed and Its Uses.

PMID- 29639833
TI  - The Treatment of Certain Cases of Ununited Fracture.

PMID- 29639834
TI  - Hobon.

PMID- 29639835
TI  - On Wounds of the Palmar Arches.

PMID- 29639836
TI  - Successful Operation on a Very Large Vesico-Vaginal Fistula, Occurring in a Child
      Eight Years of Age.

PMID- 29639837
TI  - The New Dental Bill for 1878.

PMID- 29639838
TI  - A Case of Arsenical Poisoning Treated with Dialyzed Iron.

PMID- 29639839
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29639841
TI  - Meetings of Societies.

PMID- 29639840
TI  - Concerning the So-Called Fistula Auris Congenita: Anomaly of Formation.

PMID- 29639842
TI  - Balanitis; Oil Dressing.

PMID- 29639843
TI  - The Electric Telephone as a Means of Testing or Measuring the Hearing Power.

PMID- 29639844
TI  - The Theory and Practice of Non-Restraint in the Treatment of the Insane.

PMID- 29639845
TI  - On Sanitary Inspection.

PMID- 29639847
TI  - Cases of Congenital Displacement of Both Crystalline Lenses.

PMID- 29639846
TI  - Tapping the Uterus.

PMID- 29639848
TI  - Fracture of the Neck of the Scapula.

PMID- 29639849
TI  - Correspondence.

PMID- 29639850
TI  - On Retention of Urine in the Female.

PMID- 29639851
TI  - Chancroids.

PMID- 29639852
TI  - Meetings of Societies.

PMID- 29639853
TI  - Catheter Broken off after Making a False Passage, Extracted by Perineal Section.

PMID- 29639855
TI  - The Condition of the Hymen and Its Remains by Cohabitation, Childbearing, and
      Lying-In.

PMID- 29639854
TI  - Cases of Aneurism of the Aorta, Treated by Iodide of Potassium.

PMID- 29639856
TI  - The Dull Wire Curette in Gynecological Practice.

PMID- 29639857
TI  - Sewer-Gas and Ear Disease: A Record of Struggles with Foul Drains and Other
      Unsanitary Conditions.

PMID- 29639859
TI  - List of Successful Candidates for Appointments as Surgeons in H. M. Medical
      Service.

PMID- 29639858
TI  - Ulceration of the Rectum; Treatment.

PMID- 29639860
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29639861
TI  - Structure of a Channelled Polypus of the Cervix.

PMID- 29639862
TI  - The Theory and Practice of Non-Restraint in the Treatment of the Insane.

PMID- 29639863
TI  - Royal Colleges of Physicians and Surgeons, Edinburgh.

PMID- 29639864
TI  - Non-Symmetry of the Human Form.

PMID- 29639865
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29639866
TI  - The Sewage Question.

PMID- 29639867
TI  - Diffuse Spermatic Aneurism.

PMID- 29639868
TI  - Cases of Aneurism of the Aorta, Treated by the Iodide of Potassium.

PMID- 29639869
TI  - Placenta Praevia, or Unavoidable Haemorrhage.

PMID- 29639870
TI  - Fibroma Vaginae.

PMID- 29639871
TI  - Tapping the Male Bladder in Operations on Urethral Fistulae.

PMID- 29639872
TI  - Dearth of Candidates for the Army Medical Service.

PMID- 29639873
TI  - Meetings of Societies.

PMID- 29639874
TI  - Use of Indiarubber in Surgery.

PMID- 29639875
TI  - List of Gentlemen Who Passed Their First Professional Examination.

PMID- 29639876
TI  - Complete Torsion of the Cervix Uteri (with Considerable Thickening and Dilatation
      of the Os) of a Cow.

PMID- 29639877
TI  - Knot on the Umbilical Cord Formed during Pregnancy.

PMID- 29639878
TI  - Social Psychiatry. Being the Morison Lectures for 1931 at the Royal College of
      Physicians, Edinburgh.

PMID- 29639879
TI  - Ununited Fractures of the Clavicle.

PMID- 29639880
TI  - Potassium Thiocyanate in the Treatment of Patients with Hypertension.

PMID- 29639881
TI  - The Problem of Obesity.

PMID- 29639883
TI  - Bacterial or Infective Endocarditis. The Gibson Lectures for 1930: Lecture II.

PMID- 29639882
TI  - The Course and Prognosis of Myocardial Infarction.

PMID- 29639884
TI  - Pregnancy and Hyperthyroidism.

PMID- 29639886
TI  - Antenuptial Examination.

PMID- 29639887
TI  - The "Vital" Factor in Diet: A Theory of the Nature of Vitamins.

PMID- 29639885
TI  - Social Psychiatry. Being the Morison Lectures for 1931 at the Royal College of
      Physicians, Edinburgh.

PMID- 29639888
TI  - Localized Congenital Defects of the Scalp.

PMID- 29639889
TI  - Rectal Stenosis Following Radium Treatment of Cervical Cancer.

PMID- 29639890
TI  - The Treatment of Spondylolisthesis.

PMID- 29639891
TI  - Osteodystrophy from Cattle Disease.

PMID- 29639892
TI  - Parathyreoidectomy in Osteodystrophia Fibrosa.

PMID- 29639893
TI  - Bacterial or Infective Endocarditis. The Gibson Lectures for 1930: Lecture I.

PMID- 29639894
TI  - Acetylcholine Hypodermically in Varicose Ulcers.

PMID- 29639896
TI  - Salicylates in the Prevention of Rheumatic Manifestations.

PMID- 29639895
TI  - Acholuric Jaundice Complicated by Bacillus coli Septicaemia.

PMID- 29639897
TI  - The Active Constituent of Liver Extract.

PMID- 29639899
TI  - Auriculae.

PMID- 29639898
TI  - The Influence of Acid-Forming and Base-Forming Diets.

PMID- 29639901
TI  - Vesical Syphilis.

PMID- 29639900
TI  - Spinal Anaesthesia.

PMID- 29639902
TI  - Recurrent Gelatinous Cysts of the Fingers.

PMID- 29639903
TI  - The Evolution of Modern Medicine, with Special Reference to Medical Research.

PMID- 29639904
TI  - Retrospect and Prospect.

PMID- 29639905
TI  - Centenarian Pathology.

PMID- 29639907
TI  - Tuberculous Subdeltoid Bursitis.

PMID- 29639906
TI  - The Detection and Estimation of Lactose in Urine.

PMID- 29639908
TI  - The Effect of Acidic and Basic Diets in Chronic Nephritis.

PMID- 29639909
TI  - The Radium Treatment of Primary Carcinoma of the Breast.

PMID- 29639910
TI  - Ileocaecal Lymphosarcoma in a Child.

PMID- 29639911
TI  - Regeneration of Peripheral Nerves: An Experimental Study.

PMID- 29639913
TI  - Manic-Depressive Psychosis in Identical Twins.

PMID- 29639912
TI  - Puerperal Tetanus.

PMID- 29639914
TI  - Mediastinal Tumour. Sarcoma of the Heart.

PMID- 29639916
TI  - Arterial Encephalography.

PMID- 29639917
TI  - Arteriography in Gangrene.

PMID- 29639915
TI  - The Care of the Surgical Diabetic.

PMID- 29639919
TI  - Dehydration in Intestinal Obstruction.

PMID- 29639918
TI  - Pernicious Anaemia: A Clinical Study of Recent Cases, with Special Reference to
      Prognosis and Treatment.

PMID- 29639920
TI  - Local Vascular Changes in Splenic Anaemia.

PMID- 29639922
TI  - Chronic Pudendal Hypertrophy.

PMID- 29639921
TI  - Acute Volvulus of the Stomach.

PMID- 29639923
TI  - Notes.

PMID- 29639924
TI  - The Sedimentation Rate of the Erythrocytes in Chronic Arthritis.

PMID- 29639925
TI  - Fibroma of the Biceps Muscle.

PMID- 29639926
TI  - Some Observations on Tuberculosis in the Hebrides, with Special Reference to
      Milk.

PMID- 29639927
TI  - Thoracoplasty in Pulmonary Tuberculosis, with a Discussion of Six Cases.

PMID- 29639928
TI  - Some Orthopaedic Problems.

PMID- 29639929
TI  - The Milk Supply of the Country: Policy?

PMID- 29639931
TI  - Enteric Tuberculosis.

PMID- 29639930
TI  - Tuberculous Hyperplasia of the Large Intestine.

PMID- 29639932
TI  - Notes.

PMID- 29639933
TI  - Intrathoracic Tuberculosis of Childhood.

PMID- 29639934
TI  - Microbic Dissociation; with Reference to the Attenuated Tubercle Bacillus of
      Calmette and Guerin (B.C.G.).

PMID- 29639935
TI  - Irradiated Ergosterol in Tuberculosis.

PMID- 29639936
TI  - Primary Tuberculosis of the Patella.

PMID- 29639937
TI  - Tuberculous Pericarditis in the Senile.

PMID- 29639939
TI  - Clinical Meeting.

PMID- 29639938
TI  - Some Local and General Problems in Tuberculosis Administration.

PMID- 29639940
TI  - Colonial Lunacy Boards; with Special Reference to New Zealand.

PMID- 29639941
TI  - Absorption of Insoluble Matter.

PMID- 29639942
TI  - Retention of Urine. Puncture of the Bladder with Dieulafoy's Instrument.

PMID- 29639943
TI  - Anti-Odontalgics.

PMID- 29639945
TI  - Apomorphia.

PMID- 29639944
TI  - On the Relative Weight of the Brain in the Sane and Insane.

PMID- 29639946
TI  - On Simple Menorrhagia and Simple Metrorrhagia.

PMID- 29639947
TI  - Meetings of Societies.

PMID- 29639948
TI  - The Treatment of Heart Disease.

PMID- 29639950
TI  - On the Diagnosis of Syphilis from the Microscopic Examination of the Blood.

PMID- 29639949
TI  - Medical News.

PMID- 29639951
TI  - Penetrating Gunshot Wound of the Cranium; Recovery with the Ball Still in the
      Brain.

PMID- 29639952
TI  - The Lung Test.

PMID- 29639953
TI  - Notes of Successful Operations on Aged Patients.

PMID- 29639955
TI  - Cases of Vesico-Vaginal Fistula.

PMID- 29639956
TI  - On the Treatment of Club-Foot.

PMID- 29639954
TI  - Obturator Hernia.

PMID- 29639957
TI  - Compound Syrup of Assafoetida.

PMID- 29639958
TI  - On a Form of Fracture of the Bones of the Face, and Its Diagnosis.

PMID- 29639959
TI  - On Leprosy at Hankow.

PMID- 29639960
TI  - Meetings of Societies.

PMID- 29639961
TI  - On Menstrual Coagula.

PMID- 29639962
TI  - Traumatic Tetanus Cured with Hydrate of Chloral.

PMID- 29639963
TI  - Physiological and Therapeutical Effects of Antidestructive Alimentation.

PMID- 29639964
TI  - Correspondence.

PMID- 29639966
TI  - Medical News.

PMID- 29639965
TI  - Clinical Lectures on Diseases of the Heart.

PMID- 29639967
TI  - Procidentia of the Pelvic Viscera.

PMID- 29639968
TI  - On the Treatment of Strangulated Hernia by the Removal of Air by Subcutaneous
      Puncture.

PMID- 29639969
TI  - On Vascular Murmurs within the Lungs.

PMID- 29639970
TI  - Medical News.

PMID- 29639971
TI  - Some of the Medico-Legal Relations of Insanity to Will-Making.

PMID- 29639972
TI  - Artificial Production of Epilepsy in Guineapigs.

PMID- 29639973
TI  - Correspondence.

PMID- 29639974
TI  - On the Sanitary Aspect of the Sewage Question; with Remarks on a Little-Noticed
      Cause of Typhoid Fever, and Other Zymotics.

PMID- 29639975
TI  - On the Therapeutical Value of the Hypodermic Injection of Ergotine in
      Haemoptysis.

PMID- 29639977
TI  - On Earache.

PMID- 29639976
TI  - Report on Toxicology, Forensic Medicine, and Hygiene.

PMID- 29639978
TI  - Pythogenic Fever in Reykjavik during the Summer of 1871.

PMID- 29639979
TI  - Meetings of Societies.

PMID- 29639980
TI  - On the Stability and Health, the Ovulation and Granulation of the Organism, and
      the Degeneration of Tissue.

PMID- 29639981
TI  - On the Use of Bromide of Pottassium in Epilepsy.

PMID- 29639983
TI  - Notes on Chloral.

PMID- 29639984
TI  - Letters to the Editor.

PMID- 29639982
TI  - On the Nutrition of Muscular and Pulmonary Tissue in Health and in Consumption;
      with Remarks on the Colloid Condition of Matter.

PMID- 29639985
TI  - Letters to the Editor.

PMID- 29639986
TI  - A Concise History of the Royal Infirmary, Edinburgh: Being an Address Read before
      the Royal Medical Society of Edinburgh, 1st Dec. 1871.

PMID- 29639987
TI  - Colonial Lunacy Boards; with Special Reference to New Zealand.

PMID- 29639988
TI  - Case of Haemorrhage Resulting from an Internal Wound of the OEsophagus Treated by
      Operation.

PMID- 29639989
TI  - Medical News.

PMID- 29639990
TI  - Meetings of Societies.

PMID- 29639991
TI  - Case of Strychnia-Poisoning, Treated by the Administration of Chloral Hydrate.

PMID- 29639992
TI  - Some of the Medico-Legal Relations of Insanity to Will-Making.

PMID- 29639993
TI  - Notes of a Case of Ligature of the Subclavian Artery under Somewhat Unusual
      Circumstances.

PMID- 29639994
TI  - Notes from Practice.

PMID- 29639996
TI  - Meetings of Societies.

PMID- 29639995
TI  - Cases from Practice, with Clinical Remarks.

PMID- 29639997
TI  - On the Nature and Development of Cystic Tumours of the Breast.

PMID- 29639999
TI  - A Case of Obstruction of the Bowels, Attended by Unusual Symptoms; with Remarks.

PMID- 29639998
TI  - On Antiseptic Surgery.

PMID- 29640000
TI  - The Nature of Rotheln or German Measles: Being Part of an Inaugural Thesis
      Commended by the Medical Faculty, Edinburgh Universiry, 1871.

PMID- 29640001
TI  - Medical News.

PMID- 29640002
TI  - Dysmenorrhoea.

PMID- 29640004
TI  - On Subcutaneous Injection of Ergotine in Varix.

PMID- 29640003
TI  - Cures for Coryza.

PMID- 29640005
TI  - On the Action of Chloral Hydrat.

PMID- 29640006
TI  - Edible Snails.

PMID- 29640007
TI  - Meetings of Societies.

PMID- 29640008
TI  - Xylol in Smallpox.

PMID- 29640009
TI  - On the Use of the Bowl during Delivery.

PMID- 29640010
TI  - Remarks on the "Health Resorts" of Europe.

PMID- 29640012
TI  - On the Treatment of Hyperpyrexia by the External Application of Cold.

PMID- 29640011
TI  - Medical News.

PMID- 29640014
TI  - Removal of Corns.

PMID- 29640013
TI  - Pleuro-Pericarditis-Paracentesis Pericardii.

PMID- 29640015
TI  - A Novel Plan for Soothing Children.

PMID- 29640016
TI  - Case of Recurrent Secondary Haemorrhage after Amputation of the Leg, Successfully
      Treated by Ligature of the Femoral.

PMID- 29640017
TI  - On the Treatment of Dilatation of the Stomach by the Method of Kussmaul; with
      Cases.

PMID- 29640018
TI  - Coexistence of Smallpox and Cowpox.

PMID- 29640019
TI  - Some of the Medico-Legal Relations of Insanity to Will-Making.

PMID- 29640021
TI  - The Use of Barnes's Dilators in the Treatment of Complete Placenta Praevia. With
      Two Illustrative Cases.

PMID- 29640020
TI  - Insanity Dependent upon Constitutional Syphilis.

PMID- 29640023
TI  - Endoarteritis Chronica Deformans, and Its Relation to Rupture of the Heart.

PMID- 29640022
TI  - Edinburgh University Graduation.

PMID- 29640024
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29640025
TI  - English Practitioners and Practice at the End of the Seventeenth and Commencement
      of the Eighteenth Centuries, Portrayed by Themselves.

PMID- 29640026
TI  - A New Method of Wound-Drainage.

PMID- 29640027
TI  - On the Etiology and History of Leprosy.

PMID- 29640028
TI  - Puerperal Fever and Septicaemia: Their Relations and Probable Identity.

PMID- 29640029
TI  - A Successful Case of Ovariotomy; Tumour Sessile; Cauterization.

PMID- 29640031
TI  - List of Successful Indian Medical Candidates.

PMID- 29640030
TI  - Malta Fever.

PMID- 29640032
TI  - Diphtheria and Croup:-What Are They?

PMID- 29640034
TI  - Chancellor Inglis: A Graduation Song for 1876.

PMID- 29640033
TI  - On Passive Cerebral Pressure.

PMID- 29640035
TI  - Personal Experience of Death from Aneurism and Disease of the Heart in the
      Service: A Clinical Note.

PMID- 29640037
TI  - Abeles on Sugar in Urine.

PMID- 29640036
TI  - Cases of Paraplegia.

PMID- 29640038
TI  - Vivisection: A Satire.

PMID- 29640040
TI  - On an Outbreak of Diphtheria in Auchtergaven, Perthshire; with Remarks.

PMID- 29640039
TI  - Malta Fever.

PMID- 29640041
TI  - Appointment.

PMID- 29640042
TI  - Causes of Gleet.

PMID- 29640043
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29640044
TI  - Cases of Puerperal Fever, with Reference to Epidemic Origin.

PMID- 29640045
TI  - Meetings of Societies.

PMID- 29640046
TI  - Sclerosis in Scattered Patches.

PMID- 29640047
TI  - Diphtheria: Typical Cases, in Illustration of Its Diagnosis, Prognosis, and
      Treatment; Together with Remarks on the Signification of Albuminuria in That
      Disease.

PMID- 29640048
TI  - On the Formation of an Artificial Ureter.

PMID- 29640049
TI  - General Medical Council.

PMID- 29640050
TI  - On the Registration Pseudonyms of Puerperal Fevers.

PMID- 29640051
TI  - Cases of Paraplegia.

PMID- 29640053
TI  - A Model Case. Successful Removal of an Extra-Uterine Faetus.

PMID- 29640052
TI  - Case of Extra-Uterine Foetation, Successfully Treated by Abdominal Section.

PMID- 29640054
TI  - Professor Lister's Address in Surgery.

PMID- 29640056
TI  - Chair of Physiology in the University of Glasgow.

PMID- 29640057
TI  - Notes on Surgical Practice among the Natives in Shanghai.

PMID- 29640055
TI  - Note in Supplement to a Previous Paper, Entitled, "Diphtheria and Croup: What Are
      They?"

PMID- 29640059
TI  - Exposure of a Spiritualist by Physicians.

PMID- 29640058
TI  - Compound Fractures Treated Antiseptically in the Greenock Infirmary, during the
      Course of Twelve Months.

PMID- 29640060
TI  - On the Etiology and History of Leprosy.

PMID- 29640061
TI  - Case of Puerperal Scarlatina.

PMID- 29640062
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29640064
TI  - Chair of Practice of Physic in the University of Edinburgh.

PMID- 29640063
TI  - Notes on Salicylic Acid.

PMID- 29640065
TI  - Puerperal Fever: Some Practical Clinical Facts.

PMID- 29640068
TI  - Syphilis as Affecting the Bursae.

PMID- 29640066
TI  - On Salicylate of Quinine as an Antipyretic.

PMID- 29640067
TI  - Reports of Cases Treated in Leith Hospital.

PMID- 29640069
TI  - Sclerosis in Scattered Patches.

PMID- 29640070
TI  - Arsenic in the Treatment of Skin Diseases.

PMID- 29640071
TI  - Meetings of Societies.

PMID- 29640072
TI  - Cases of Paraplegia.

PMID- 29640073
TI  - English Practitioners and Practice at the End of the Seventeenth and Commencement
      of the Eighteenth Centuries, Portrayed by Themselves.

PMID- 29640074
TI  - The Recognition of the Blood of Man and of Animals in Dried Spots in Medico-Legal
      Investigations.

PMID- 29640075
TI  - Case of Operation for Strangulated Inguinal Hernia.

PMID- 29640076
TI  - Antiseptic for Country Practice.

PMID- 29640077
TI  - Primary Carcinoma of the Kidneys in Childhood.

PMID- 29640078
TI  - The Medical Society of Chile.

PMID- 29640080
TI  - Cases from Practice.

PMID- 29640079
TI  - A Case of Haemathidrosis.

PMID- 29640081
TI  - Anti-Vivisectors in the Box.

PMID- 29640082
TI  - University of Edinburgh Degrees of Bachelor and Doctor of Science in the
      Department of Public Health.

PMID- 29640083
TI  - The Active Element in Vaccine Lymph.

PMID- 29640084
TI  - Poisoning by Digitalis.

PMID- 29640085
TI  - On Ejaculation of Semen in Persons Who Are Hanged.

PMID- 29640086
TI  - On the Structure of Three Cervical Polypi.

PMID- 29640087
TI  - A Case of Disease of the Tongue.

PMID- 29640088
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29640089
TI  - Sclerosis in Scattered Patches.

PMID- 29640090
TI  - The Treatment of Erysipelas by the Muriated Tincture of Iron.

PMID- 29640091
TI  - Personal Experience of Death from Aneurism and Disease of the Heart in the
      Service: A Clinical Note.

PMID- 29640092
TI  - Paraffin Epithelioma of the Scrotum.

PMID- 29640093
TI  - Case of Spontaneous Circular Rupture of the Aorta.

PMID- 29640095
TI  - List of Candidates Who Received Degrees in the University of Edinburgh, 1st
      August 1876.

PMID- 29640094
TI  - Portuguese Medical Literature.

PMID- 29640096
TI  - Opium.

PMID- 29640097
TI  - Information Regarding Medical Education and Examinations.

PMID- 29640098
TI  - List of Hospitals, Dispensaries, Etc., in Connexion with the Medical Schools of
      Scotland.

PMID- 29640100
TI  - Successful Candidates for the Army Medical Service.

PMID- 29640099
TI  - Notes on a Case of Sunstroke.

PMID- 29640101
TI  - On Malta Fever.

PMID- 29640103
TI  - Fothergillian Gold Medal.

PMID- 29640102
TI  - Course of Study Required by the Various Boards of the United Kingdom.

PMID- 29640104
TI  - Mercurial Poisoning from Canned Meats.

PMID- 29640105
TI  - Sclerosis in Scattered Patches.

PMID- 29640106
TI  - 1836-1876.

PMID- 29640107
TI  - An Original Suicide.

PMID- 29640108
TI  - Army Medical School.

PMID- 29640110
TI  - Preliminary Examinations for the Diplomas of the Royal Colleges of Physicians and
      Surgeons of Edinburgh, with Examination Papers.

PMID- 29640109
TI  - Datura.

PMID- 29640111
TI  - Compound Fracture of the Patella.

PMID- 29640113
TI  - Litholysis.

PMID- 29640112
TI  - Medical Schools of Scotland, 1876-77.

PMID- 29640114
TI  - Force of Ciliary Motion.

PMID- 29640116
TI  - Indian Medical Service.

PMID- 29640115
TI  - On the Causes of the Hypertrophy of the Vascular System in Granular Degeneration
      of the Kidney.

PMID- 29640117
TI  - Cupping and Ice in Acute Gastritis.

PMID- 29640119
TI  - Army Medical Department.

PMID- 29640118
TI  - Case of Transverse Fracture of the Patella, Treated by a New Method.

PMID- 29640120
TI  - Navy Medical Department.

PMID- 29640122
TI  - Conservative Surgery.

PMID- 29640121
TI  - Local Treatment of Burns.

PMID- 29640123
TI  - Dyspnoea from the Dropping of a Molar Tooth into the Trachea.

PMID- 29640124
TI  - On the Human Voice.

PMID- 29640125
TI  - The Father of Medicine.

PMID- 29640126
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29640127
TI  - On Giant Urticaria.

PMID- 29640128
TI  - Condylomatous Excrescences of the Anus Treated by Escharotics.

PMID- 29640129
TI  - Medico-Chirurgical Society-Discussion on Mr Annandale's Paper on Excision of the
      Joint between the Astragalus and Os Calcis.

PMID- 29640130
TI  - Surgical Therapeutic: Antiseptic Surgery at Edinburgh.

PMID- 29640131
TI  - Notes of Cases of Disease of the Heart; with Remarks on the Effect of Over-Work
      on the Heart and Aorta.

PMID- 29640132
TI  - Clinical Notes on Some Fevers at Naples.

PMID- 29640133
TI  - Stirling District Lunacy Notes: A Case of Child-Murder.

PMID- 29640134
TI  - Treatment of Erysipelas by the Muriated Tincture of Iron.

PMID- 29640135
TI  - Salicine as an Antipyretic.

PMID- 29640137
TI  - Meetings of Societies.

PMID- 29640136
TI  - Statistics of Amputation of the Thigh in Bengal.

PMID- 29640138
TI  - The Circulating Fluid: The Harveian Oration delivered 30th May 1930.

PMID- 29640139
TI  - Pyelography by Intravenous Injection.

PMID- 29640140
TI  - Rupture of the Psoas Muscle.

PMID- 29640141
TI  - Acetylcholine in Embolism.

PMID- 29640142
TI  - Spontaneous Umbilical Parturition.

PMID- 29640143
TI  - Spasmodic Narrowing of the OEsophagus.

PMID- 29640144
TI  - The Use of Epinephrine as a Diagnostic Test for Angina Pectoris.

PMID- 29640146
TI  - Tumours of Bone.

PMID- 29640145
TI  - Clinical Meeting.

PMID- 29640148
TI  - Accidental Corneal Vaccination.

PMID- 29640147
TI  - On the Paramastoid Process in the Human Subject and Its Association with
      Deformation of the Atlas and Epistropheus.

PMID- 29640149
TI  - The Evolution of Voice in Animals and in Man; a Study in Comparative Physiology.

PMID- 29640150
TI  - The Cartilages of Conjugation in Bone-Growth.

PMID- 29640151
TI  - Notes.

PMID- 29640153
TI  - Migraine Equivalent.

PMID- 29640152
TI  - On the Use of Common Compounds of Carbon in Disease, with Special Reference to
      Cholera.

PMID- 29640154
TI  - The Basophilic Substance of the Erythrocyte.

PMID- 29640155
TI  - Raynaud's Disease.

PMID- 29640156
TI  - Electrospun Cytocompatible Polycaprolactone Blend Composite with Enhanced
      Wettability for Bone Tissue Engineering.
AB  - Electrospinning is recently used in tissue engineering due to their excellent
      ability to mimic the structure of extra cellular matrix (ECM), a prerequisite for
      creating an optimal microenvironment for cell growth. Electrospun nanofibrous
      composite scaffolds consisting of polycaprolactone (PCL)/Poly(1,4-butylene
      adipate-co-polycaprolactam) (PBAPCL) blend with hydroxyapatite (HA) have been
      fabricated to enhance the wettability and osseointegrative properties. Fourier
      transform-infrared spectroscopy (FT-IR) confirmed molecular interactions of the
      polymer blend along with the presence of HA. X-ray diffraction analysis (XRD)
      indicated semi-crystalline nature of the mat and also the presence of HA in the
      composite mat. The morphology of the fibres, were analyzed using scanning
      electron microscopy (SEM) and the diameter was found to be in the range of 400
      600 nm. The composite fibers were of larger diameter compared to their polymer
      counterparts. Improved wettability of the electrospun composite mat has been
      observed by contact angle analysis. In vitro cell culture studies by Live/Dead
      assay and MTT using human osteosarcoma (HOS) cells indicated the cytocompatible
      nature of electrospun mat which was further confirmed by cell adhesion using SEM
      and Actin-phalloidin staining. Addition of PBAPCL and HA to PCL have a beneficial
      effect on cell growth and proliferation thereby making the composite, a
      prospective scaffold for bone tissue engineering applications.

PMID- 29640158
TI  - Monthly Retrospect of Obstetrics and Gynaecology.

PMID- 29640157
TI  - Report Prepared by the Puerperal Fever Committee of the Berlin Obstetrical
      Society, and Laid before the Prussian Minister of Public Health-Dr Falk.

PMID- 29640159
TI  - The Physics of the Bladder and Ureters.

PMID- 29640160
TI  - Clinical Lecture on the Lochial Discharge, Delivered at the Glasgow Maternity
      Hospital.

PMID- 29640161
TI  - Chronic Cervical Metritis Treated by Interstitial Injection, Coupled with
      Dilatation.

PMID- 29640162
TI  - On Death from the Insufficient Administration of Chloroform.

PMID- 29640163
TI  - Dearth of Candidates for the Army Medical Service.

PMID- 29640164
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29640165
TI  - Indian Medical Service.

PMID- 29640166
TI  - Meetings of Societies.

PMID- 29640167
TI  - Correspondence.

PMID- 29640168
TI  - Medical Schools of Scotland.

PMID- 29640169
TI  - Army Medical Department.

PMID- 29640170
TI  - Army Medical School.

PMID- 29640171
TI  - The Physics of the Bladder and Ureters.

PMID- 29640172
TI  - Preliminary Examinations for the Diplomas of the Royal Colleges of Physicians and
      Surgeons of Edinburgh.

PMID- 29640174
TI  - 1878-9-Address to Students.

PMID- 29640173
TI  - Navy Medical Department.

PMID- 29640175
TI  - Occasional Periscope of Dermatology.

PMID- 29640177
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29640176
TI  - Cases of Intra-Cranial Tumour.

PMID- 29640178
TI  - On Curettes and Curetting.

PMID- 29640179
TI  - The Sewage Question.

PMID- 29640181
TI  - List of Hospitals, Etc., in Connexion with the Medical Schools of Scotland.

PMID- 29640180
TI  - Displacement of the Bladder and Peritoneum in the Male by Distention of the
      Rectum.

PMID- 29640182
TI  - Day-Schools for the Deaf and Dumb.

PMID- 29640183
TI  - Information Regarding Medical Education and Examinations.

PMID- 29640184
TI  - On Hydrophobia: Its History and Cure.

PMID- 29640185
TI  - A Case of Poisoning by Chloral Hydrate; Introducing a New Test.

PMID- 29640187
TI  - On the Etiology and History of Leprosy.

PMID- 29640186
TI  - The Sewage Question.

PMID- 29640189
TI  - Meetings of Societies.

PMID- 29640188
TI  - Alcohol in Disease.

PMID- 29640190
TI  - Chrysophanic Acid in Von Hebra's Clinic at Vienna.

PMID- 29640191
TI  - Cases of Hemiplegic Aphasia.

PMID- 29640192
TI  - Notes of Three Cases of Accidental Haemorrhage, with Remarks.

PMID- 29640193
TI  - Notes of Cases of Spinal Curvature Treated after Dr Sayre's Method.

PMID- 29640194
TI  - Case of Unreduced Pott's Fracture Remedied by Operation.

PMID- 29640195
TI  - Medicine Chest of Thevenot's Globules.

PMID- 29640196
TI  - Monthly Retrospect of Obstetrics and Gynaecology.

PMID- 29640197
TI  - On the Treatment of Spasmodic Asthma.

PMID- 29640198
TI  - List of Candidates for Commissions as Surgeons at London and Netley.

PMID- 29640200
TI  - On Hydrophobia: Its History and Cure.

PMID- 29640199
TI  - Comments on a Case of Hyperpyrexia.

PMID- 29640201
TI  - Notes on a Case of Umbilical Urinary Fistula.

PMID- 29640202
TI  - Practical Observations on Some of the More Common Diseases of Early Life.

PMID- 29640205
TI  - Hunter's Carbolic Acid Injections.

PMID- 29640204
TI  - Address to the Medical Graduates in the University of Edinburgh, 1st August 1878.

PMID- 29640203
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29640207
TI  - Meetings of Societies.

PMID- 29640206
TI  - Cases of Intracranial Tumour.

PMID- 29640208
TI  - Some Account of a Disease Called "Shima-Mushi," or "Island-Insect Disease," by
      the Natives of Japan; Peculiar, It Is Believed, to That Country, and Hitherto Not
      Described.

PMID- 29640209
TI  - The Cause of Distortions in the Spinal Paralysis of Children.

PMID- 29640211
TI  - The Risks and Treatment of Intra-Uterine Hydrocephalus as a Complication of
      Labour, with the History of a Case.

PMID- 29640210
TI  - Note on the Physiology of Respiration.

PMID- 29640212
TI  - Drs Lossen and Braun on Neurectomy.

PMID- 29640213
TI  - A Few Practical Remarks on the More Common Fevers of Syria.

PMID- 29640214
TI  - Monthly Retrospect of Obstetrics and Gynaecology.

PMID- 29640215
TI  - Heroic Aural Surgery.

PMID- 29640216
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29640217
TI  - On the Etiology and History of Leprosy.

PMID- 29640218
TI  - Refracture for the Relief of Deformity Following Badly-Treated Fracture of the
      Extremities.

PMID- 29640220
TI  - The Sewage Question.

PMID- 29640219
TI  - Note of a Case of Retroversion of the Gravid Uterus.

PMID- 29640221
TI  - Trellis-Work Dressing for Fractures.

PMID- 29640222
TI  - On the Modes of Administering Mercury in Syphilis.

PMID- 29640223
TI  - Bucellas Hock.

PMID- 29640224
TI  - On Croup: Its Nature and Treatment.

PMID- 29640225
TI  - Monthly Retrospect of Obstetrics and Gynaecology.

PMID- 29640226
TI  - On the Etiology and History of Leprosy.

PMID- 29640227
TI  - Spontaneous Amputation of the Thigh.

PMID- 29640228
TI  - Cases of Amenorrhaea.

PMID- 29640229
TI  - An Improved Method of Treating Club-Foot.

PMID- 29640230
TI  - Cases of Intra-Cranial Tumour.

PMID- 29640231
TI  - Periscope of Otology.

PMID- 29640233
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29640232
TI  - Cases of Hystero-Epilepsy.

PMID- 29640234
TI  - Case of Poisoning by Opium.

PMID- 29640235
TI  - Case of Idiopathic Anaemia.

PMID- 29640237
TI  - Australian Gum Trees.

PMID- 29640236
TI  - Occasional Periscope of Dermatology.

PMID- 29640238
TI  - Practical Observations on Some of the More Common Diseases of Early Life.

PMID- 29640240
TI  - Three Cases of Pneumothorax Occurring as an Early Symptom of Pulmonary Disease.

PMID- 29640239
TI  - Gastric Ulcers and Perforating Ulcer of Duodenum after a Burn.

PMID- 29640241
TI  - Notes of an Epidemic of Typhoid Fever, with Special Reference to Its Antipyretic
      Treatment.

PMID- 29640242
TI  - Note on the Practically Absolute Safety of Profoundly Induced Anaesthesia in
      Childbirth as Compared with Its Employment in General Surgery.

PMID- 29640244
TI  - On Infantile Habiliments.

PMID- 29640243
TI  - Note on the Treatment of Rupture of the Ligamentum Patellae.

PMID- 29640245
TI  - Foreign Health Statistics.

PMID- 29640246
TI  - Lister's Antiseptic Method in Ovariotomy.

PMID- 29640247
TI  - Meetings of Societies.

PMID- 29640249
TI  - Pancreotomy.

PMID- 29640248
TI  - Original Observations and Experiments on the Nervous System, and on the Process
      of Innervation and Nutrition.

PMID- 29640250
TI  - A Certain Sign of Real Death for Physicians and Non-Professional Men.

PMID- 29640251
TI  - Notes on Surgical Practice among the Natives in Shanghai.

PMID- 29640253
TI  - On the Distinction between Inflammatory and Diphtheritic Croup.

PMID- 29640254
TI  - "Shut Your Mouth and Save Your Life:" Being Remarks on Mouth-Breathing, and Some
      of Its Consequences, Especially to the Apparatus of Hearing: A Contribution to
      the AEtiology of Ear-Disease.

PMID- 29640252
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29640255
TI  - On Some of the Relations of the Foetal Head to Rupture of the Perineum and
      Injuries of the External Genital Organs.

PMID- 29640256
TI  - On the External Use of Salicylate of Iron.

PMID- 29640257
TI  - On the Importance of the Uterine Ebb as a Factor in Pelvic Surgery.

PMID- 29640258
TI  - Case of Accidental Penetration of Abdomen (per Vaginam); with Remarks.

PMID- 29640259
TI  - On the Physiological Position of the Uterus.

PMID- 29640260
TI  - On Excision of the Joint between the Os Calcis and Astragalus.

PMID- 29640261
TI  - On the Application of the Nitrate of Silver to Ulcers.

PMID- 29640263
TI  - Meetings of Societies.

PMID- 29640262
TI  - Details of a Case, in Which Death Is Supposed to Have Resulted from Ether Used as
      an Anaesthetic.

PMID- 29640264
TI  - Monthly Report of the Morpeth Rural Sanitary Authority.

PMID- 29640267
TI  - Notes of Cases of Susceptibility of the Action of Medicines.

PMID- 29640266
TI  - The Umbilical Cord Felt through the Abdominal Wall.

PMID- 29640265
TI  - Is Syphilis Inoculable through Milk?

PMID- 29640269
TI  - Successful Inoculation of Cancer in Dogs.

PMID- 29640268
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29640270
TI  - Royal Medical Society.

PMID- 29640271
TI  - Scald of Glottis.

PMID- 29640272
TI  - Note on the Treatment of Pityriasis Versicolor.

PMID- 29640273
TI  - On the Therapeutic Action of the Secale Cornutum.

PMID- 29640274
TI  - Spindle-Celled Sarcoma.

PMID- 29640275
TI  - On Rupture of the Urinary Bladder and Its Surgical Treatment.

PMID- 29640276
TI  - A Steam Spray-Producer for Hospital Use.

PMID- 29640277
TI  - Dr Terrillon on Sprain of the "Medio-Tarsal" Articulation.

PMID- 29640278
TI  - Case of Lead-Poisoning.

PMID- 29640279
TI  - Army Medical Service-Successful Candidates.

PMID- 29640280
TI  - Correspondence.

PMID- 29640281
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29640282
TI  - Meetings of Societies.

PMID- 29640283
TI  - On the Condition of the Cervix Uteri in the Latter Months of Utero-Gestation.

PMID- 29640284
TI  - The Diagnosis of General Paralysis of the Insane.

PMID- 29640285
TI  - Professor Dolbeau on the Treatment of False Joint.

PMID- 29640286
TI  - Case of Aneurism in Lateral Ventrical of Brain.

PMID- 29640287
TI  - On Filiform Bougies: Their Uses and Advantages.

PMID- 29640288
TI  - Case of Hernia, with Traumatic Rupture and Formation of Faecal Fistula.

PMID- 29640289
TI  - Correspondence.

PMID- 29640290
TI  - Case in Which a Knitting-Needle Penetrated the Brain through the Orbit.

PMID- 29640291
TI  - Fissures Occurring in Long Bones.

PMID- 29640292
TI  - Experimental Researches on the Action and Sounds of the Heart.

PMID- 29640293
TI  - Professor Blum on Traumatic Shock.

PMID- 29640294
TI  - On the Therapeutics of Aloin.

PMID- 29640295
TI  - Societe Clinique de Paris.

PMID- 29640296
TI  - Gurjon-Oil Treatment of Leprosy.

PMID- 29640297
TI  - The Astringent Action of Salicylic Acid.

PMID- 29640298
TI  - Professor Dolbeau on Reduction of Dislocations of the Hip by Flexion and
      Rotation.

PMID- 29640299
TI  - Dualistic Theory of Venereal Sores.

PMID- 29640300
TI  - Case of Badly-United Fracture of the Femur Treated by Sawing across the Bone at
      Its Angle, with Antiseptic Precautions.

PMID- 29640301
TI  - Note on Esmarch's Operation for the Relief of Permanent Closure of the Jaws.

PMID- 29640302
TI  - Treatment of Wounds of the Radial and Ulnar Arteries by Acupressure.

PMID- 29640303
TI  - Clinical Study of the Treatment of Some Complications of the Urethra.

PMID- 29640304
TI  - List of Indian Medical Candidates.

PMID- 29640305
TI  - Case of Tetanus Occurring after a Burn.

PMID- 29640306
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29640307
TI  - The Operative Treatment of Genu Valgum.

PMID- 29640309
TI  - On Oil of Turpentine in Sciatica.

PMID- 29640308
TI  - Five Cases of Complete Inversion of the Uterus; with Remarks on the Operation for
      Chronic Inversion.

PMID- 29640311
TI  - Endowment of a Demonstratorship of Physiology in the University of Glasgow, Etc.

PMID- 29640310
TI  - On the Influence of Modern Education on Health.

PMID- 29640312
TI  - Meetings of Societies.

PMID- 29640314
TI  - Gangrenous Tuberculo-Ulcerating Syphilid.

PMID- 29640313
TI  - On the Etiology and History of Leprosy.

PMID- 29640316
TI  - The Spread of Cancer.

PMID- 29640315
TI  - Correspondence.

PMID- 29640317
TI  - Letter from Mentone.

PMID- 29640318
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29640319
TI  - Faecal Accumulations, Simulating Utero-Ovarian Tumours.

PMID- 29640320
TI  - Case of Empyema.

PMID- 29640321
TI  - So-Called Septic Agents in Situations Inaccessible to Air.

PMID- 29640322
TI  - A Case of Lymphadenoma (with Leukemia?).

PMID- 29640323
TI  - Two Cases of Puerperal Pleuropneumonia.

PMID- 29640324
TI  - Meetings of Societies.

PMID- 29640325
TI  - Resignation of Sir Robert Christison.

PMID- 29640326
TI  - Litholysis.

PMID- 29640327
TI  - Struck by Lightning, Etc.

PMID- 29640329
TI  - Note on the Use of the Stethoscope in Obstetrics.

PMID- 29640328
TI  - Lecture on the Behaviour of Bloodclot under Aseptic Conditions.

PMID- 29640330
TI  - Incompatibility as Applied to Medicine.

PMID- 29640331
TI  - Note of a Case of Painless Second Stage of Labour in a Primipara.

PMID- 29640332
TI  - Correspondence.

PMID- 29640333
TI  - Staff-Surgeon Reid's Case of Aneurism Successfully Treated by Esmarch's Elastic
      Bandage and Compressor.

PMID- 29640334
TI  - Varieties of Infecting Chancre.

PMID- 29640335
TI  - Correspondence.

PMID- 29640336
TI  - On the Operative Treatment of Internal Piles.

PMID- 29640338
TI  - Meetings of Societies.

PMID- 29640337
TI  - William Pulteney Alison, His Work in Relation to Harvey: Being the Harveian
      Discourse to the Edinburgh Society, 12th April 1877.

PMID- 29640339
TI  - Lunacy Administration in Scotland.

PMID- 29640340
TI  - On a Remarkable Case of Spermatocele Occurring in Mr Lister's Practice in the
      Royal Infirmary, Edin.

PMID- 29640341
TI  - Duplay on Antiseptic Surgery.

PMID- 29640343
TI  - Lunacy Laws.

PMID- 29640342
TI  - Abstract of a Lecture on Pernicious Anaemia.

PMID- 29640344
TI  - Professor Lister.

PMID- 29640345
TI  - Salomonsen on Bacteria in Metastatic Abscesses.

PMID- 29640346
TI  - Cases Treated in Leith Hospital.

PMID- 29640348
TI  - Pasteur, Joubert, and Chamberland on the Germ Theory.

PMID- 29640347
TI  - Murchison Memorial.

PMID- 29640349
TI  - Periscope of Syphilology.

PMID- 29640351
TI  - On the Unity of Poison in Scarlatina, Puerperal Fever, Typhoid, Diphtheria,
      Erysipelas, Etc.

PMID- 29640350
TI  - My Professional Peers at Cork.

PMID- 29640352
TI  - Menthol: An Anti-Neuralgic.

PMID- 29640353
TI  - Brief Notes of a Case of Double Floating Kidney, Diagnosed during Life, and
      Verified by Post-Mortem Examination.

PMID- 29640354
TI  - On Foreign Bodies in the Air-Passages, with Cases.

PMID- 29640355
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29640356
TI  - Murchison Memorial.

PMID- 29640357
TI  - Army Medical School, Netley.

PMID- 29640358
TI  - On a Source of Error in the Clinical Estimation of the Elongation of the Cervix
      during Labour.

PMID- 29640359
TI  - Occasional Periscope of Dermatology.

PMID- 29640360
TI  - A Short Sketch of the Recent Visitation of the Plague in Bagdad and Its Vicinity.

PMID- 29640361
TI  - Practical Observations on Some of the More Common Diseases of Early Life.

PMID- 29640363
TI  - Address to the Medical Graduates in the University of Edinburgh, 1st August 1879.

PMID- 29640362
TI  - Periscope of Ophthalmology.

PMID- 29640364
TI  - Hilliard's Surgical Cabinet.

PMID- 29640365
TI  - Meetings of Societies.

PMID- 29640366
TI  - Correction.
AB  - [This corrects the article on p. 165 in vol. 25.].

PMID- 29640367
TI  - Ethidene Dichloride as an Anaesthetic.

PMID- 29640368
TI  - Monthly Retrospect of Obstetrics and Gynaecology.

PMID- 29640370
TI  - Periscope of Ophthalmology.

PMID- 29640369
TI  - Bernard and Pasteur on Alcoholic Fermentation.

PMID- 29640371
TI  - Transfusion of Human Blood.

PMID- 29640372
TI  - The Treatment of Aneurisms by Electrolysis.

PMID- 29640374
TI  - Monthly Retrospect of Obstetrics and Gynaecology.

PMID- 29640373
TI  - Periscope of Otology and Ophthalmology.

PMID- 29640376
TI  - On Anaesthesia and Anaesthetics.

PMID- 29640375
TI  - On the Etiology and History of Leprosy.

PMID- 29640377
TI  - The Historical Evolution of the Sense of Colour; Refutation of the Theories of
      Gladstone and Magnus.

PMID- 29640378
TI  - Hypodermic Injection of Morphia.

PMID- 29640380
TI  - On the Occurrence of the Common Fluke (Fasciola Hepatica) in the Human Subject.

PMID- 29640379
TI  - Statistical Report of Results of Operations Performed.

PMID- 29640381
TI  - Monthly Report of the Progress of Therapeutics.

PMID- 29640382
TI  - Meetings of Societies.

PMID- 29640383
TI  - Statistical Society, Howard Medal.

PMID- 29640384
TI  - Observations on Some Points in Dextral Valvular Disease of the Heart, Being a
      Graduation Thesis.

PMID- 29640386
TI  - Observations on Some Points in Dextral Valvular Disease of the Heart, Being a
      Graduation Thesis.

PMID- 29640385
TI  - Note on the Active Treatment of Severe Cases of Primary Keratitis.

PMID- 29640387
TI  - Occasional Periscope of Dermatology.

PMID- 29640389
TI  - Dr Cameron on Potts's Fracture of the Fibula.

PMID- 29640388
TI  - Correspondence.

PMID- 29640390
TI  - Monthly Retrospect of Obstetrics and Gynaecology.

PMID- 29640392
TI  - Periscope of Ophthalmology.

PMID- 29640391
TI  - The Differential Diagnosis of Lead Encephalopathy and Intra-Cranial Tumours.

PMID- 29640393
TI  - Periscope of Otology.

PMID- 29640394
TI  - On the Medical Uses of Electricity: A Clinical Lecture.

PMID- 29640396
TI  - Case of Perityphlitis.

PMID- 29640395
TI  - Statistical Report of Results of Operations Performed.

PMID- 29640397
TI  - Note on the Excretion of Urea.

PMID- 29640398
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29640399
TI  - The Therapeutics of Belladonna in Intestinal Obstruction.

PMID- 29640400
TI  - Rotten Teeth: A Rhapsody, with a Remedy.

PMID- 29640401
TI  - Practical Observations on Some of the More Common Diseases of Early Life.

PMID- 29640402
TI  - Meetings of Societies.

PMID- 29640403
TI  - Two Cases of Cerebral Abscesses.

PMID- 29640404
TI  - Address to Students, 1879-80.

PMID- 29640405
TI  - Indian Medical Service.

PMID- 29640406
TI  - Meetings of Societies.

PMID- 29640407
TI  - Navy Medical Department.

PMID- 29640408
TI  - List of Hospitals, Etc., in Connexion with the Medical Schools of Scotland.

PMID- 29640409
TI  - Information Regarding Medical Education and Examinations.

PMID- 29640410
TI  - Perthshire Medical Association.

PMID- 29640411
TI  - Occasional Periscope of Dermatology.

PMID- 29640413
TI  - Periscope of Otology and Ophthalmology.

PMID- 29640412
TI  - Monthly Report of the Progress of Therapeutics.

PMID- 29640414
TI  - Postponement of Examination for the Army Medical Department.

PMID- 29640415
TI  - The Use of the Volsella in Gynecology.

PMID- 29640417
TI  - Army Medical Department.

PMID- 29640416
TI  - Report of Cases Treated in Connexion with the Edinburgh Royal Maternity and
      Simpson Memorial Hospital during the First Quarter, with Remarks.

PMID- 29640418
TI  - Remarks on the Examination and Classification of Cases of Colour-Blindness.

PMID- 29640420
TI  - Medical Schools of Scotland.

PMID- 29640419
TI  - A Short Sketch of the Recent Visitation of the Plague in Bagdad and Its Vicinity.

PMID- 29640421
TI  - Army Medical School.

PMID- 29640422
TI  - The Treatment of Aneurisms by Electrolysis.

PMID- 29640423
TI  - Preliminary Examinations for the Diplomas of the Royal Colleges of Physicians and
      Surgeons of Edinburgh, during the Year 1879-80.

PMID- 29640425
TI  - Case of Prolapse of Uterus, with Eversion of Vagina, Complicating Labour.

PMID- 29640424
TI  - Observations on the Nature, Symptoms, and Treatment of Constricted or
      Strangulated Hernia, Reduced En Bloc.

PMID- 29640426
TI  - Note of a Case of Labour, Complicated with Locomotor Ataxia.

PMID- 29640427
TI  - Cases of Intra-Cranial Tumour.

PMID- 29640428
TI  - Report of a Case of Puerperal Eclampsia.

PMID- 29640429
TI  - Periscope of Ophthalmology and Otology.

PMID- 29640430
TI  - Monthly Retrospect of Obstetrics and Gynaecology.

PMID- 29640431
TI  - Treatment of Puerperal Septicaemia.

PMID- 29640432
TI  - Occasional Periscope of Dermatology.

PMID- 29640433
TI  - On the Adenoid Tumours of the Naso-Pharynx, and Their Influence on the Hearing,
      Breathing, and Phonation, and on Their Treatment.

PMID- 29640434
TI  - Examination of Candidates for British Medical Service.

PMID- 29640436
TI  - On the Etiology and History of Leprosy.

PMID- 29640435
TI  - Recurrent Tumours in the Parotid Region.

PMID- 29640437
TI  - Case of Hystero-Epilepsy, Aggravated by Pregnancy and Necessitating Premature
      Labour.

PMID- 29640438
TI  - Observations on Some Points in Dextral Valvular Disease of the Heart.

PMID- 29640439
TI  - Monthly Report of the Progress of Therapeutics.

PMID- 29640440
TI  - Meetings of Societies.

PMID- 29640441
TI  - Correspondence.

PMID- 29640442
TI  - The Bearings of the Shape of the Foetal Head on the Mechanism of Labour.

PMID- 29640443
TI  - Messrs T. & H. Smith & Co. and the Sydney International Exhibition.

PMID- 29640444
TI  - Murchison Memorial.

PMID- 29640445
TI  - Monthly Report of the Progress of Therapeutics.

PMID- 29640446
TI  - Periscope of Syphilology.

PMID- 29640448
TI  - Meetings of Societies.

PMID- 29640447
TI  - Case of Reunion of a Severed Portion of Finger.

PMID- 29640449
TI  - Occasional Periscope of Dermatology.

PMID- 29640451
TI  - The New Royal Infirmary.

PMID- 29640450
TI  - The Study of Mental Disease; Being the Introductory Lecture Delivered in the
      University of Edinburgh, on the Institution of the Lectureship on Mental
      Diseases, May 1879.

PMID- 29640452
TI  - Lipaemia and Fat Embolism in the Fatal Dyspnoea and Coma of Diabetes.

PMID- 29640453
TI  - On the Operation for Stone in the Female Bladder.

PMID- 29640454
TI  - Spurious Hydrophobia in the Lower Animals.

PMID- 29640455
TI  - Aural Periscope.

PMID- 29640456
TI  - On the Adenoid Tumours of the Naso-Pharynx, and Their Influence on the Hearing,
      Breathing, and Phonation, and on Their Treatment.

PMID- 29640458
TI  - Royal Visit to the New Hertford British Hospital, Paris.

PMID- 29640457
TI  - Note on a Case of Lateral Curvature of the Spine Treated by a New Method.

PMID- 29640459
TI  - Sudden Death from Aneurism by Rupture.

PMID- 29640461
TI  - To See Ourselves as Others See Us.

PMID- 29640460
TI  - Correspondence.

PMID- 29640462
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29640463
TI  - On the Etiology and History of Leprosy.

PMID- 29640465
TI  - Pleural Effusion, Its Diagnosis and Treatment.

PMID- 29640464
TI  - Idiopathic or Progressive Pernicious Anaemia, with Cases.

PMID- 29640466
TI  - Practical Observations on Some of the More Common Diseases of Early Life.

PMID- 29640467
TI  - Conference of Dentists.

PMID- 29640468
TI  - Appointment to the Chair of Clinical Surgery.

PMID- 29640469
TI  - On Puerperal Fever.

PMID- 29640470
TI  - Italian Medical Periodicals.

PMID- 29640471
TI  - Case of Molluscous Tumour of the Ear, Complicated with Polypi and a Fistulous
      Opening behind the Auricle Communicating with the Internal Ear, and Stretching up
      to a Cavity on the Temple Two Inches above the Auricle under the Muscular
      Structures.

PMID- 29640472
TI  - Treatment of Anomalies in the Spanning of the Membrana Tympani.

PMID- 29640473
TI  - On the Human Voice.

PMID- 29640474
TI  - On the Management of Natural Labour.

PMID- 29640475
TI  - Doctors in the English Army.

PMID- 29640476
TI  - Concerning the Normal Arched or Spanned Conditions of the Healthy Membrana
      Tympani in the Human Subject.

PMID- 29640477
TI  - Notes on a Case of Chronic Chloral Poisoning.

PMID- 29640478
TI  - Tubercular Leprosy.

PMID- 29640479
TI  - Army Medical Candidates.

PMID- 29640481
TI  - The Anti-Vivisection Act.

PMID- 29640480
TI  - On Certain Manifestations of Gout, Rheumatism, and Rheumatoid Disease.

PMID- 29640483
TI  - List of Candidates Who Received Medical Degrees in the University of Edinburgh.

PMID- 29640482
TI  - Reports of Cases from the Medical Mission Register of Neyoor, Travancore, South
      India.

PMID- 29640484
TI  - Excision of the Lower End of the Rectum in Cases of Cancer.

PMID- 29640486
TI  - Candidates for India Medical Service.

PMID- 29640485
TI  - Notes and Remarks on Three Cases of Puerperal Convulsions.

PMID- 29640487
TI  - The Model Physician.

PMID- 29640489
TI  - Recent Progress in Surgery.

PMID- 29640488
TI  - Opium in Relation to Population.

PMID- 29640490
TI  - Death and Danger from Ether.

PMID- 29640491
TI  - On the Nature and Mechanism of Spontaneous Rupture of the Uterus in Its Cervical
      Portion.

PMID- 29640492
TI  - Puerperal Embolism.

PMID- 29640493
TI  - Meetings of Societies.

PMID- 29640494
TI  - Over-Population-Effects Produced by It, and the Remedies Proposed.

PMID- 29640495
TI  - Dilatation of the Ureters and Renal Pelves.

PMID- 29640496
TI  - Meetings of Societies.

PMID- 29640497
TI  - What Is the Use of a Hospital?

PMID- 29640498
TI  - Note on a Mode of Saving Blood in Great Operations.

PMID- 29640499
TI  - Notes on Surgical Practice among the Natives of Shanghai.

PMID- 29640500
TI  - On the Etiology and History of Leprosy.

PMID- 29640501
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29640502
TI  - Venomous Animals.

PMID- 29640503
TI  - A New Way of Applying Mr Lister's Method of Treating Wounds.

PMID- 29640505
TI  - Some Remarks on Fibrous Tumours of the Uterus.

PMID- 29640504
TI  - Mercury in Syphilis.

PMID- 29640507
TI  - Penetrating Wound of the Abdomen, with Prolapse of the Omentum.

PMID- 29640506
TI  - Notes of a Case of Scirrhus in Both Mammae.

PMID- 29640508
TI  - Giant-Cells in Syphilomata.

PMID- 29640509
TI  - Meetings of Societies.

PMID- 29640510
TI  - Case of Emphysema during Labour-Short Forceps-Rupture of Perineum-Operation for
      Its Restoration.

PMID- 29640511
TI  - Notes of a Case of Supplementary Axillary Mammae.

PMID- 29640512
TI  - Sound Vibrations of Soap-Film Membranes.

PMID- 29640513
TI  - Ophthalmology in Its Relation to General Medicine.

PMID- 29640514
TI  - Gangrenous Tuberculo-Ulcerating Syphilid.

PMID- 29640515
TI  - The Surgical Function of the Omentum.

PMID- 29640516
TI  - Description of an Acardiac Foetus.

PMID- 29640517
TI  - Urethral Polypus.

PMID- 29640518
TI  - Dislocation of the Thumb Backwards.

PMID- 29640519
TI  - Case of Procidentia Uteri.

PMID- 29640520
TI  - Subscapular Friction.

PMID- 29640521
TI  - Chair of Clinical Surgery.

PMID- 29640523
TI  - Disease from Worry and Mental Strain. Phenomena of Reduced Vascular Tension.

PMID- 29640522
TI  - Case of Triplets, Complicated with Puerperal Convulsions after Delivery.

PMID- 29640524
TI  - Chronic Endo-Carditis, Independent of Rheumatism and Amenable to Treatment,
      Simulating Confirmed and Irremediable Valvular Disease.

PMID- 29640526
TI  - MM. Vincent and Guignard on Disease and Excision of the Calcaneum.

PMID- 29640525
TI  - Case of Infanticide by Asphyxia, in Which the Four Cavities of the Heart Were
      Found Empty.

PMID- 29640527
TI  - Chair of Materia Medica.

PMID- 29640528
TI  - Case of Spontaneous Version after the Rupture of the Membranes in a Primipara.

PMID- 29640529
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29640530
TI  - Observations on the Hypodermic Injection of Remedies, with More Especial
      Reference to the Hypodermic Injection of Morphia and Cold Water.

PMID- 29640531
TI  - The Effect of Inaudible Vibrations upon Sensitive Flames.

PMID- 29640532
TI  - Preliminary Examinations for the Diplomas of the Royal Colleges of Physicians and
      Surgeons of Edinburgh.

PMID- 29640533
TI  - Medical Schools of Scotland.

PMID- 29640534
TI  - Dr Matthews Duncan.

PMID- 29640535
TI  - A Synopsis of Private Obstetrical Practice for Forty-Two Years Previous to 1st
      January 1876.

PMID- 29640536
TI  - Navy Medical Department.

PMID- 29640537
TI  - Summary of Dr Marion Sim's Paper on the Discovery of Anaesthesia.

PMID- 29640538
TI  - Typical Tubercular Leprosy.

PMID- 29640539
TI  - List of Hospitals, Etc., in Connexion with the Medical Schools of Scotland.

PMID- 29640540
TI  - Mammary Abscess Treated Antiseptically.

PMID- 29640541
TI  - Surgical Statistics.

PMID- 29640542
TI  - Excision of the Lower End of the Rectum in Cases of Cancer.

PMID- 29640543
TI  - Information Regarding Medical Education and Examinations.

PMID- 29640544
TI  - Surgical Notes.

PMID- 29640545
TI  - Note of a Case of Haematocele Simulating a Retroverted Gravid Uterus.

PMID- 29640546
TI  - Hertford British Hospital of Paris.

PMID- 29640547
TI  - Formation of Epidermis by the Transplanting of Hairs.

PMID- 29640548
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29640549
TI  - Army Medical Department.

PMID- 29640550
TI  - Case of Pyaemia.

PMID- 29640551
TI  - On Tubercle in the Human Lung.

PMID- 29640552
TI  - Sequeloe of the So-Called "Paludal Fever of Mauritius".

PMID- 29640553
TI  - Case of a Lacerated Wound of the Axilla.

PMID- 29640554
TI  - Indian Medical Service.

PMID- 29640556
TI  - Professional Ethics and Etiquette.

PMID- 29640555
TI  - On the Auricular Impulse.

PMID- 29640557
TI  - Army Medical School.

PMID- 29640558
TI  - Treatment of Anomalies in the Spanning of the Drumhead.

PMID- 29640559
TI  - Coal-Gas Poisoning. Successful Case.

PMID- 29640560
TI  - The Antiseptic Dressing of Wounds.

PMID- 29640561
TI  - Antiseptic Treatment of Chronic Bursitis.

PMID- 29640563
TI  - Advice to a Friend.

PMID- 29640562
TI  - Introductory Address, Delivered at the Opening of the Edinburgh Medical School on
      30th October 1877.

PMID- 29640565
TI  - Meetings of Societies.

PMID- 29640564
TI  - Functions of the Spleen.

PMID- 29640567
TI  - On the Etiology and History of Leprosy.

PMID- 29640566
TI  - Medical Specimens.

PMID- 29640568
TI  - Ueber eine neue Methode zur Vervollstandigung des Unterrichtes in der
      Gynakologie.

PMID- 29640570
TI  - The Survival of the Fittest.

PMID- 29640571
TI  - Notice of Capo d'Istria.

PMID- 29640569
TI  - A. Blum on Diseases of the Urethra in Women.

PMID- 29640573
TI  - Insanity and the Revival Movement.

PMID- 29640572
TI  - Practical Observations on Some of the More Common Diseases of Early Life.

PMID- 29640574
TI  - On a New Preparation for Allaying Irritation of the Actively Secreting Mammary
      Glands.

PMID- 29640575
TI  - Dinner to Dr J. Matthews Duncan.

PMID- 29640576
TI  - Observations on Antipyretics.

PMID- 29640577
TI  - Eczema among Woodcutters.

PMID- 29640578
TI  - A Preliminary Note upon the Occurrence of Incomplete Development of the Striated
      Muscle Fibre as a Cause of Certain Congenital Deformities of the Extremities.

PMID- 29640579
TI  - Case of Myositis Ossificans Progressiva.

PMID- 29640580
TI  - The Relation of Hyperfunction of the Posterior Lobe of the Hypophysis to
      Eclampsia and Nephropathy of Pregnancy.

PMID- 29640582
TI  - The Heart in Lobar Pneumonia.

PMID- 29640581
TI  - The Treatment of Chorea by Nirvanol.

PMID- 29640583
TI  - Studies on Blood and Tissue Reactions: III. The Specificity of Tissue and Blood
      Reaction.

PMID- 29640584
TI  - Peptic Ulcer and Its Treatment: A Study of 200 Hospital Cases.

PMID- 29640585
TI  - Artificial Pneumothorax.

PMID- 29640586
TI  - Edward Clark Chair of Child Life and Health: Inaugural Address.

PMID- 29640587
TI  - Dupuytren's Contraction and Dysparathyreoidism.

PMID- 29640588
TI  - Multiple Duodenal Ulcers.

PMID- 29640589
TI  - Heart Block in Toxic Goitre: A Report of Two Cases.

PMID- 29640590
TI  - Varicose Veins in Pregnancy.

PMID- 29640591
TI  - Notes.

PMID- 29640592
TI  - Myositis Ossificans Progressiva.

PMID- 29640593
TI  - Valedictory Address on "Fifty Years of Medicine".

PMID- 29640594
TI  - Clinical Meeting.

PMID- 29640595
TI  - Therapeutic Pneumothorax.

PMID- 29640596
TI  - Notes.

PMID- 29640597
TI  - Periarterial Sympathectomy in Radiodermatitis.

PMID- 29640598
TI  - Cirsoid Aneurysm.

PMID- 29640599
TI  - Arteriectomy.

PMID- 29640600
TI  - Epilepsy after Ligation of Carotid Artery and Internal Jugular Vein.

PMID- 29640602
TI  - Myositis Ossificans Progressiva.

PMID- 29640601
TI  - Brain Involvement in Head Injury. A Preliminary Study of 200 Cases.

PMID- 29640604
TI  - Osteoma of the Tongue.

PMID- 29640603
TI  - Traumatic Venous Thrombosis in the Upper Extremity.

PMID- 29640605
TI  - Clinlcal Meeting.

PMID- 29640606
TI  - Calcium Chloride to Relieve Peristaltic Pain.

PMID- 29640607
TI  - Studies on Blood and Tissue Reactions: I. Notes on Technique of Blood
      Examination.

PMID- 29640608
TI  - Glandular Fever or Infective Mononucleosis.

PMID- 29640610
TI  - Hyperinsulinism.

PMID- 29640611
TI  - The Treatment of Nephritic OEdema by Acid.

PMID- 29640609
TI  - The Relation of Glycosuria to Glycaemia and the Determination of the Renal
      Threshold for Glucose.

PMID- 29640612
TI  - The Genesis of Blood Platelets.

PMID- 29640613
TI  - The Treatment of Pernicious Anaemia with Campolon.

PMID- 29640614
TI  - Complement Fixation in Meningococcal Infections as an Aid to Diagnosis: With Note
      on Clinical Standpoint.

PMID- 29640616
TI  - Extract of Suprarenal Cortex in the Treatment of Addison's Disease.

PMID- 29640615
TI  - A Clinico-Pathological Study of Carcinoma of the Stomach, Using Large Microscopic
      Sections and Dissecting the Lymphatic Spread.

PMID- 29640617
TI  - Operations on the Nerves of the Urinary Bladder.

PMID- 29640619
TI  - Insulin and the Healing of Fractures.

PMID- 29640618
TI  - Milker's Whitlow.

PMID- 29640620
TI  - Notes.

PMID- 29640621
TI  - The Genesis of Blood Platelets.

PMID- 29640622
TI  - Underlying Principles in the Treatment of Bone and Joint Tuberculosis.

PMID- 29640623
TI  - Human Tuberculosis of Bovine Origin.

PMID- 29640624
TI  - Angina Agranulocytica and Its Treatment.

PMID- 29640625
TI  - Tuberculosis Schemes-Administrator and Clinician.

PMID- 29640626
TI  - Pregnancy in Tuberculosis.

PMID- 29640628
TI  - Primary OEsophageal Tuberculosis.

PMID- 29640627
TI  - Pneumoperitoneum in the Treatment of Tuberculous Enterocolitis.

PMID- 29640629
TI  - Remarks by the President: The Incidence of the Bovine Type of Tuberculous
      Infection in Scotland.

PMID- 29640630
TI  - Remarks by the President (Sir Robert Philip).

PMID- 29640631
TI  - The Incidence of the Human and Bovine Types of Tuberculous Infection in Children
      Living in the West of Scotland.

PMID- 29640632
TI  - Some Observations on the Death-Rate from Tuberculosis in Glasgow.

PMID- 29640633
TI  - Some Observations on Tuberculides.

PMID- 29640634
TI  - The Cause and Treatment of Displacements of the Heart in Pulmonary Tuberculosis.

PMID- 29640635
TI  - Protection against Tuberculosis.

PMID- 29640637
TI  - Monthly Retrospect of Obstetrics and Gynaecology.

PMID- 29640638
TI  - On the Adenoid Tumours of the Naso-Pharynx, and Their Influence on the Hearing,
      Breathing, and Phonation, and on Their Treatment.

PMID- 29640636
TI  - Harveian Discourse, 14th April 1879.

PMID- 29640639
TI  - Reduction en masse of a Strangulated Inguinal Hernia in a Woman.

PMID- 29640640
TI  - Ligature of the Ischial Artery.

PMID- 29640641
TI  - Cases of Intra-Cranial Tumour.

PMID- 29640642
TI  - Haematemesis in the Newly-Born Child (Illustrated by a Case Associated with the
      Haemorrhagic Diathesis in the Mother).

PMID- 29640644
TI  - Monthly Report of the Progress of Therapeutics.

PMID- 29640645
TI  - Presentation to Dr Fowler, Corstorphine.

PMID- 29640643
TI  - Meetings of Societies.

PMID- 29640647
TI  - Occasional Periscope of Dermatology.

PMID- 29640646
TI  - Sudden Death from Aneurism by Rupture.

PMID- 29640648
TI  - Aural Periscope.

PMID- 29640649
TI  - On the Prevention of Mammary Abscess.

PMID- 29640650
TI  - Spurious Hydrophobia in the Lower Animals.

PMID- 29640651
TI  - Observations on Some Forms of Sterility and on Placenta Praevia in First Labours:
      With Illustrative Cases.

PMID- 29640652
TI  - Surgical Cases-Injuries and Operations.

PMID- 29640653
TI  - Army Medical School, Netley.

PMID- 29640654
TI  - Remarks on the Etiology of "Puerperal Fever".

PMID- 29640655
TI  - Royal Maternity Hospital.

PMID- 29640657
TI  - Case of Aneurism of the Aorta Projecting into the Neck, and Accompanied by
      Contraction of the Pupil on the Affected Side.

PMID- 29640656
TI  - On Croup: Its Nature and Treatment.

PMID- 29640658
TI  - Medicine.

PMID- 29640659
TI  - On the Os Sacrum Considered as Forming Part of the Vault of the Pelvis, and on
      Its Function in the Development of the Lateral Expansion of That Cavity.

PMID- 29640660
TI  - Diseases of the Spinal Cord and Its Membranes.

PMID- 29640661
TI  - Case of Encephaloid Cancer of the Right Kidney and of the Lung, Simulating
      Ascites, and Developed at a Very Early Age.

PMID- 29640663
TI  - Surgery.

PMID- 29640662
TI  - Case of Labour Complicated with Emphysema.

PMID- 29640664
TI  - Varieties.

PMID- 29640666
TI  - Obstetrical Society of Edinburgh.

PMID- 29640665
TI  - Case of Traumatic Rupture of the Duodenum.

PMID- 29640667
TI  - On the Extensive Diffusion and Frequency of Starch Corpuscles, in the Tissues of
      the Human Body.

PMID- 29640668
TI  - Observations on Croup:-Symptomatography.

PMID- 29640669
TI  - Case of Aneurism of the Aorta, Occupying the Arch, and Obstructing the Left
      Carotid and Subclavian Arteries; with Lesser Aneurisms, One of Which Opened into
      the Left Auricle; and with Aortic and Mitral Regurgitation.

PMID- 29640670
TI  - Hints to Students on the Prosecution of Their Studies: Being Extracts from an
      Address Delivered at Surgeons' Hall, Edinburgh, at the Commencement of the Winter
      Session 1854.

PMID- 29640671
TI  - The Month.

PMID- 29640672
TI  - Case of Branchial Fistula of the Neck.

PMID- 29640673
TI  - Medical Schools of Scotland, 1855-6.

PMID- 29640674
TI  - On the Composition of Bread.

PMID- 29640675
TI  - Case of Tubercular Leprosy or Elephantiasis Groecorum: Condensed from a Paper
      Read before the Medico-Chirurgical Society of Edinburgh.

PMID- 29640676
TI  - Case of Rupture of the Aorta.

PMID- 29640678
TI  - Course of Study Required by the Various Boards of the United Kingdom.

PMID- 29640677
TI  - Town Council Proceedings.

PMID- 29640679
TI  - Proceedings of the Poor-Law Commissioners of England.

PMID- 29640680
TI  - Diseases of the Spinal Cord and Its Membranes.

PMID- 29640681
TI  - Case of Un-United Fracture of Humerus, Cured by Resection.

PMID- 29640682
TI  - On the Speculum in Local Bleeding in Diseases of the Uterus.

PMID- 29640683
TI  - Notes on the Application of Statistics, to Questions in Medical Science,
      Particularly as to the External Causes of Diseases.

PMID- 29640684
TI  - Quarterly Report of Cases Occurring at the Edinburgh Eye-Infirmary.

PMID- 29640685
TI  - Edinburgh Obstetrical Society.

PMID- 29640686
TI  - List of Graduates.

PMID- 29640687
TI  - Peculiar Case of an Extensive Sanguineous Tumour, or Extravasation of Blood into
      the Substance of Thigh.

PMID- 29640688
TI  - On Synchronous, or Simultaneous Double Amputation.

PMID- 29640689
TI  - Varieties.

PMID- 29640690
TI  - Therapeutical Record.

PMID- 29640691
TI  - On Medical Evidence in the Preliminary Investigation of Criminal Cases in
      Scotland.

PMID- 29640692
TI  - On the Horizontal Curvature of the Internal Femoral Condyle: On the Movements and
      Relations of the Patella; Semilunar Cartilages; and Synovial Pads of the Human
      Knee-Joint.

PMID- 29640693
TI  - Midwifery.

PMID- 29640695
TI  - Observations on Croup:-Nosography.

PMID- 29640694
TI  - Perineal Fistula Left by the Transit of the Infant through the Perineum.

PMID- 29640696
TI  - Surgery.

PMID- 29640697
TI  - Medicine.

PMID- 29640698
TI  - Case of Femoral Hernia, Containing the Caput Coecum, and Complicated with an
      Irregular Obturator Artery Surrounding and Constricting the Protrusion.

PMID- 29640699
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29640700
TI  - The Board of Supervision.

PMID- 29640701
TI  - Quarterly Report of Cases Occurring at the Edinburgh Eye Infirmary.

PMID- 29640702
TI  - Cases and Observations in Surgery.

PMID- 29640704
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29640703
TI  - On Blood-Letting in Internal Inflammations.

PMID- 29640705
TI  - Varieties.

PMID- 29640706
TI  - Cases of Gastro-Colic Fistula, with Observations on Its Pathology, Diagnosis,
      etc.

PMID- 29640707
TI  - Toxicology.

PMID- 29640708
TI  - Medical News.

PMID- 29640709
TI  - Clinical Observations on a Characteristic of the Urine in Rheumatism and Gout,
      with Special Reference to Diathetic Diagnosis.

PMID- 29640711
TI  - Case in Which Inflammation and Ulceration of the Sound Skin Was Caused by the
      Application of a Strong Arsenical Solution.

PMID- 29640710
TI  - Account of a Species of Diarrhoea in Which the Stools Contain Fatty Corpuscles.

PMID- 29640712
TI  - Notes on the Cholera Which Appeared at Varna in the Year 1854, and More
      Especially in Her Majesty's Ship "Agamemnon," in the Black Sea, between the 1st
      August 1854, and 8th September 1855.

PMID- 29640714
TI  - Statement by the Medical Incorporations with Regard to Medical Reform.

PMID- 29640713
TI  - The Month.

PMID- 29640715
TI  - Notes on the Cholera Which Appeared at Varna in the Year 1854, and More
      Especially in Her Majesty's Ship "Agamemnon," in the Black Sea, between the 1st
      August 1854, and 8th September 1855.

PMID- 29640716
TI  - On the Prevalence of Calculus Vesicoe, and the Result of the Operation of
      Lithotomy in the Bengal Presidency.

PMID- 29640718
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29640717
TI  - Cases and Observations in Surgery.

PMID- 29640720
TI  - Varieties.

PMID- 29640719
TI  - The Doctrine of the Duration of Labour.

PMID- 29640721
TI  - Obstetrical Society of Edinburgh.

PMID- 29640722
TI  - The Month.

PMID- 29640723
TI  - Medicine.

PMID- 29640725
TI  - Royal College of Surgeons.

PMID- 29640724
TI  - Suggestions for Observations on the Influence of Cholera, and Other Epidemic
      Poisons, on the Lower Animals.

PMID- 29640726
TI  - Cases of Gastro-Colic Fistula, with Observations on Its Pathology, Diagnosis,
      etc.

PMID- 29640728
TI  - Bubo (?) within the Abdomen.

PMID- 29640727
TI  - Case of Poisoning by Aq. Ammonia.

PMID- 29640729
TI  - Hygiene.

PMID- 29640730
TI  - Reply to the Foregoing "Remarks" of Dr Gairdner.

PMID- 29640731
TI  - Successful Case of Staphylography.

PMID- 29640732
TI  - Notes on the Cholera Which Appeared at Varna in the Year 1854, and More
      Especially in Her Majesty's Ship "Agamemnon," in the Black Sea, between the 1st
      August 1854, and 8th September 1855.

PMID- 29640733
TI  - Obstetrical Society of Edinburgh.

PMID- 29640734
TI  - The Month.

PMID- 29640735
TI  - Cases and Observations in Surgery.

PMID- 29640736
TI  - Statistics.

PMID- 29640737
TI  - Midwifery.

PMID- 29640738
TI  - Remarks on Dr Bennett's Paper on Blood-Letting and Antiphlogistic Treatment, in
      the Edinburgh Medical Journal for March 1857.

PMID- 29640739
TI  - Varieties.

PMID- 29640740
TI  - Cases and Observations in Surgery.

PMID- 29640741
TI  - Half-Yearly Medical Report of Fife County Prison, Ending June 30, 1857.

PMID- 29640742
TI  - Epidemic Cholera.

PMID- 29640744
TI  - Varieties.

PMID- 29640743
TI  - Contributions to the Pathology of the Brain, Fevers, etc.

PMID- 29640745
TI  - Surgery.

PMID- 29640746
TI  - Syphilization in Norway.

PMID- 29640747
TI  - On Injections of the Bronchi in Pulmonary Diseases.

PMID- 29640748
TI  - Contribution to the Statistics of Pneumonia.

PMID- 29640749
TI  - Cases of Suicidal Poisoning with Arsenic.

PMID- 29640750
TI  - Royal College of Surgeons.

PMID- 29640751
TI  - Medicine.

PMID- 29640752
TI  - On the Compulsory and Unpaid Registration of Deaths by Medical Men.

PMID- 29640753
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29640754
TI  - The Internal Surface of the Uterus after Delivery.

PMID- 29640755
TI  - Claims of Scotch Practitioners to Practise in England.

PMID- 29640756
TI  - Phthisis and Climate.

PMID- 29640757
TI  - Medical Reform.

PMID- 29640758
TI  - Therapeutical Record.

PMID- 29640759
TI  - Introductory Address.

PMID- 29640760
TI  - Graduation Address.

PMID- 29640762
TI  - Surgery.

PMID- 29640761
TI  - Officers of the Association of the King and Queen's College of Physicians in
      Ireland, for 1857-58.

PMID- 29640763
TI  - Varieties.

PMID- 29640764
TI  - Mr Macleod's Case of Ileus.

PMID- 29640765
TI  - Medicine.

PMID- 29640766
TI  - Three Case Sof Ruptured Perineum and Sphincter Ani, in Which Operative Treatment
      Proved Successful.

PMID- 29640768
TI  - Midwifery.

PMID- 29640767
TI  - On the Quantity of Poison Which Has Been Found in the Stomach in Murder by
      Poisoning with Arsenic.

PMID- 29640769
TI  - Dr Livingstone in Edinburgh.

PMID- 29640770
TI  - Contributions to the Pathology of the Brain, Fevers, etc.

PMID- 29640771
TI  - Case of Dislocation of the Humerus Backwards.

PMID- 29640772
TI  - Course of Study Required by the Various Boards of the United Kingdom.

PMID- 29640773
TI  - Surgery.

PMID- 29640774
TI  - Cases and Observations in Surgery.

PMID- 29640775
TI  - Case of Empyema and Pneumo-Thorax; with a Peculiar Metallic Phenomenon in
      Connection with the Sounds of the Heart. Death by Epileptic Coma (Uroemic
      Poisoning).

PMID- 29640777
TI  - Notice of a Case in Which a Tumour of the Pia Mater Caused Compression of the
      Spinal Cord.

PMID- 29640776
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29640778
TI  - Letters to Dr Alison, on the Supposed Change of Type of Inflammatory Diseases.

PMID- 29640779
TI  - Medicine.

PMID- 29640780
TI  - Medical Schools of Scotland, 1857-8.

PMID- 29640781
TI  - The Month.

PMID- 29640782
TI  - Addresses of Dr Faye on Syphilization, and of Dr Clay on Ovariotomy.

PMID- 29640783
TI  - Medical Notes on India.

PMID- 29640784
TI  - Case of Ulcer of OEsophagus Perforating the Aorta.

PMID- 29640785
TI  - Preparation of Cantharidis.

PMID- 29640786
TI  - Case of Suppurating Tumour in the Groin, Resembling Hernia.

PMID- 29640787
TI  - Address Delivered to the Members of the Harveian Society of Edinburgh, at Their
      Annual Meeting Held on the 13th April, 1857.

PMID- 29640788
TI  - Varieties.

PMID- 29640790
TI  - Hints to Students: On the Prosecution of Their Studies.

PMID- 29640789
TI  - Statistics.

PMID- 29640791
TI  - Case of Enteritis, with Some Remarks on the Treatment of Inflammations.

PMID- 29640794
TI  - Case of Tracheotomy Performed on a Child Three Months Old.

PMID- 29640793
TI  - On Law and Medicine in Insanity: An Introductory Lecture.

PMID- 29640792
TI  - Case of Extreme Debility after Acute Disease, Successfully Treated by Pepsine.

PMID- 29640795
TI  - Quarterly Return of Births, Deaths, and Marriages.

PMID- 29640796
TI  - Practice of Physic.

PMID- 29640797
TI  - Epidemic of Scarlet Fever at Donaldson's Hospital during the Autumn and Winter of
      1861.

PMID- 29640798
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29640799
TI  - Varieties.

PMID- 29640800
TI  - Case of Inversion of the Uterus Occurring Spontaneously Eighty Hours after
      Delivery.

PMID- 29640801
TI  - Statistics of Prisoners: Cases of Homicidal Mania.

PMID- 29640802
TI  - On the Occurrence of Aguish Diseases on Board Ship.

PMID- 29640803
TI  - Description of the Native Operation for Depression of Cataract in India.

PMID- 29640805
TI  - Letter from Paris.

PMID- 29640804
TI  - Case of Poisoning by Sulphuric Acid.

PMID- 29640806
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29640808
TI  - Another Case of Amputation of the Thigh at Its Upper Fourth, in Which Acupressure
      Was Successfully Employed;-With Remarks.

PMID- 29640807
TI  - On the Elephantiasis Scroti of Bengal.

PMID- 29640809
TI  - Varieties.

PMID- 29640810
TI  - Contributions to the Knowledge of Osteomalacia.

PMID- 29640812
TI  - Practice of Medicine.

PMID- 29640811
TI  - Case of Strangulated Hernia, Accompanied with Chronic Abscess in the
      Neighbourhood of Poupart's Ligament.

PMID- 29640814
TI  - Professors Syme and Velpeau on the Treatment of Fracture of the Femur.

PMID- 29640813
TI  - Small-Pox and Vaccination in Campbelton, 1860-61.

PMID- 29640815
TI  - The Wire Seton in Hydrocele.

PMID- 29640816
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29640817
TI  - Contributions to the Knowledge of Osteomalacia.

PMID- 29640818
TI  - University of Edinburgh.

PMID- 29640819
TI  - Royal Medical Society of Edinburgh.

PMID- 29640820
TI  - Hygiene.

PMID- 29640821
TI  - Scottish Universities Commission.

PMID- 29640822
TI  - Case of Punctured Wound of the Brain-Recovery.

PMID- 29640823
TI  - Some Remarks on the Treatment of Scalds and Burns.

PMID- 29640824
TI  - Midwifery.

PMID- 29640825
TI  - Case of Cancer of the Coecum, Accompanied with Coeco-Duodenal and Coeco-Colic
      Fistuloe.

PMID- 29640826
TI  - Proceedings of the Edinburgh Obstetrical Society.

PMID- 29640827
TI  - Medical News.

PMID- 29640828
TI  - On the Temperature of Mineral Waters.

PMID- 29640829
TI  - Report of Clinical Cases Treated during the Session 1860-61, in the Surgical
      Wards of the Royal Infirmary.

PMID- 29640831
TI  - Jottings from the Parisian Hospitals.-No. II.

PMID- 29640830
TI  - Royal College of Physicians.

PMID- 29640832
TI  - Varieties.

PMID- 29640833
TI  - An Inquiry into the Chemistry and Properties of the Cytisus Laburnum.

PMID- 29640834
TI  - Practice of Medicine.

PMID- 29640835
TI  - Proceedings of the Edinburgh Obstetrical Society.

PMID- 29640836
TI  - On Cancrum Oris.

PMID- 29640837
TI  - Notice of Some of the Cases Treated in the Clinical Surgical Wards of the Royal
      Infirmary of Edinburgh, during February 1862.

PMID- 29640838
TI  - Materia Medica and Therapeutics.

PMID- 29640839
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29640840
TI  - Case of Coesarean Section.

PMID- 29640842
TI  - Report of the Edinburgh Ear Dispensary; with Notes of One Hundred Cases of
      Diseases of the Ear, Treated in Succession during the First Months of 1861.

PMID- 29640841
TI  - Half-Yearly Report of Cases Occurring at the Edinburgh Eye Infirmary, 140 George
      Street.

PMID- 29640843
TI  - Report on the Causes of Death among the Assured in the North British Insurance
      Company, from the Commencement of the Business in 1823, up to 31st December 1860:
      Being a Period of Thirty-Seven Years.

PMID- 29640845
TI  - Quarterly Return of Births, Deaths, and Marriages.

PMID- 29640844
TI  - Scottish Universities Commission.

PMID- 29640847
TI  - Remarks on Certain Medico-Legal Aspects of the Maclean Will Case.

PMID- 29640846
TI  - Notice of Some of the Cases Treated in the Clinical Surgical Wards of the Royal
      Infirmary of Edinburgh, during January 1862.

PMID- 29640848
TI  - Jottings from the Parisian Hospitals.

PMID- 29640849
TI  - Midwifery.

PMID- 29640850
TI  - Case of Suppuration within the Peritoneum.

PMID- 29640851
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29640852
TI  - Proceedings of the Edinburgh Obstetrical Society.

PMID- 29640853
TI  - Cases of Poisoning by Goats' Milk.

PMID- 29640854
TI  - Important Trial for Alleged Malpraxis.

PMID- 29640855
TI  - Surgery.

PMID- 29640856
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29640858
TI  - Diphtheria and Its Sequels: A Narrative.

PMID- 29640857
TI  - Notice of Some of the Cases Treated in the Clinical Surgical Wards of the Royal
      Infirmary of Edinburgh, during March 1862.

PMID- 29640859
TI  - Arsenic and Sesquicarbonate of Ammonia in Ague.

PMID- 29640860
TI  - On the Removal of Stumps, Decayed Teeth, etc.

PMID- 29640861
TI  - Jottings from the Parisian Hospitals.-No. III.

PMID- 29640862
TI  - University Appointments.

PMID- 29640864
TI  - An Inquiry into the Chemistry and Properties of the Cytisus Laburnum.

PMID- 29640863
TI  - Observations on the Absorbing Power of the Human Skin.

PMID- 29640865
TI  - Royal College of Physicians of London.

PMID- 29640866
TI  - Proceedings of the Edinburgh Obstetrical Society.

PMID- 29640867
TI  - Quarterly Report on Physiology.

PMID- 29640868
TI  - On Diseases of the Cerebellum.

PMID- 29640869
TI  - Erratum.
AB  - [This corrects the article on p. 960 in vol. 7.].

PMID- 29640870
TI  - Phosphorus Pills.

PMID- 29640871
TI  - Medical News.

PMID- 29640872
TI  - Case of Numerous Cutaneous Cysts Scattered over the Body.

PMID- 29640873
TI  - Salicin in Obstinate Diarrhoea.

PMID- 29640875
TI  - The Use of the Electro-Magnetic Current in the Second Stage of Labour.

PMID- 29640876
TI  - Excision of the Thyroid Gland.

PMID- 29640874
TI  - The Febrifuge Properties of the Cinchona Alkaloids-Cinchonia, Quinidia, and
      Cinchonidia: Being the Abstract of a Thesis, for Which a Gold Medal Was Awarded
      by the Medical Faculty of the University of Edinburgh, at Graduation on 1st
      August 1872.

PMID- 29640877
TI  - The Typhoid Condition.

PMID- 29640879
TI  - Triplex Pill of Dr John W. Francis.

PMID- 29640878
TI  - On the Comparative Advantages of Forceps, of Turning, and of Premature Labour in
      Contracted Pelvis: Illustrated by the Obstetrical Histories of Two Women.

PMID- 29640880
TI  - Case of Strychnine Poisoning Successfully Treated by Atropine.

PMID- 29640882
TI  - Meetings of Societies.

PMID- 29640881
TI  - Two Cases of Intussusception in Children.

PMID- 29640884
TI  - Homines Hirsuti.

PMID- 29640883
TI  - On a Method of Operating in Certain Cases of Strangulated Hernia.

PMID- 29640885
TI  - Case of Polypus of the Cavity of the Cervix Uteri; with Its Microscopical
      Examination.

PMID- 29640887
TI  - Ice as a Remedy in Stricture.

PMID- 29640886
TI  - Medical News.

PMID- 29640888
TI  - Method of Examining and Recording Medical Cases.

PMID- 29640890
TI  - Median Lithotomy.

PMID- 29640889
TI  - The Action of Inorganic Substances When Introduced Directly into the Blood.

PMID- 29640891
TI  - On the Use and Abuse of Purgatives.

PMID- 29640892
TI  - Case of Recovery from Extensive Wound of the Brain.

PMID- 29640893
TI  - Correspondence.

PMID- 29640894
TI  - Fracture of Spine-Reduction of Displaced Fragments-Cure.

PMID- 29640895
TI  - Circular Referred to by Dr Playfair: When Cholera is Epidemic.

PMID- 29640896
TI  - Reduction of Large Herniae by Means of Indiarubber Bands.

PMID- 29640897
TI  - Intussusception-Recovery.

PMID- 29640898
TI  - Cases of Tetanus Cured by Section of Nerves.

PMID- 29640899
TI  - On the Action and Sounds of the Heart.

PMID- 29640900
TI  - Resection of Hip-Joint.

PMID- 29640901
TI  - Trachetomy in Diphtheria.

PMID- 29640902
TI  - Treatment of Diabetes by Arsenic.

PMID- 29640903
TI  - The Danger of Badly-Made and Old Catheters.

PMID- 29640904
TI  - Death from Chloroform.

PMID- 29640906
TI  - The Use and Abuse of Nux Vomica and Its Alkaloids.

PMID- 29640905
TI  - Case of Chronic Tetanus Cured by the Removal of a Cicatrix and Involved Nerve.

PMID- 29640907
TI  - On the Cause of the Prophylactic and Therapeutic Value of Table Salt, Iodide of
      Potassium, Etc.

PMID- 29640908
TI  - On the Haemorrhage That Occurs during the Continuance of Pregnancy in Cases of
      Placenta Praevia.

PMID- 29640909
TI  - Case of Chronic Abscess Treated by Carbolic Acid; with Remarks on Its Use in
      Similar Cases.

PMID- 29640910
TI  - Medical News.

PMID- 29640911
TI  - Picric Acid as Test for Albumen in Clinical Medicine.

PMID- 29640912
TI  - A Case of Intrauterine Polypus.

PMID- 29640913
TI  - Meetings of Societies.

PMID- 29640914
TI  - On the Treatment of Glandular Affections.

PMID- 29640915
TI  - Surgical Cases in Relation to Temperature.

PMID- 29640916
TI  - Extirpation of the Whole Uterus in a Case of Inversion.

PMID- 29640917
TI  - Fragmentary Remarks on New and Old Medicine.

PMID- 29640919
TI  - On the Medicinal Use of Green Soap.

PMID- 29640918
TI  - Memorandum of the Identification of Blood-Stains.

PMID- 29640920
TI  - On Darwinism in Its Relation to the Higher Faculties of Man.

PMID- 29640921
TI  - The Late Professor Goodsir and Professor Virchow.

PMID- 29640922
TI  - On Ether and Chloroform in London Practice.

PMID- 29640923
TI  - On Re-Vaccination as a Means of Preventing and "Stamping-Out" Smallpox.

PMID- 29640924
TI  - On the Value of the Corpus Luteum as a Proof of Impregnation; with a Case in
      Which an Unimpregnated Ovum Was Found in the Virgin Uterus.

PMID- 29640925
TI  - On Endometritis Decidualis Chronica, as a Cause of Abortion in Some Cases of
      Displacement of the Pregnant Uterus.

PMID- 29640926
TI  - Address to the Scottish Midland and Western Medical Association. Read at the
      Annual Meeting on 30th July 1872.

PMID- 29640927
TI  - Preliminary Examinations for the Diplomas of the Royal Colleges of Physicians and
      Surgeons of Edinburgh, during the Year 1873-74.

PMID- 29640929
TI  - Bone Absorption by Means of Giant Cells.

PMID- 29640928
TI  - Remarks on Medical Study.

PMID- 29640930
TI  - The Structure of Tendon.

PMID- 29640931
TI  - The Electrolytic Treatment of Cancer (Neftel).

PMID- 29640932
TI  - Information Regarding Medical Education and Examinations.

PMID- 29640933
TI  - Navy Medical Department.

PMID- 29640934
TI  - An Experimental Inquiry into the Physiological Actions of Theine, Caffeine,
      Guaranine, Cocaine, and Theobromine.

PMID- 29640935
TI  - Medical News.

PMID- 29640936
TI  - Medicine as a Profession: A Graduation Address, Delivered 1st August 1873.

PMID- 29640937
TI  - Indian Medical Service.

PMID- 29640939
TI  - List of Hospitals, Dispensaries, Etc., in Connexion with the Medical Schools of
      Scotland.

PMID- 29640938
TI  - On the Causes of the Predisposition to Phthisis among the Natives of the Hebrides
      and West Highlands.

PMID- 29640940
TI  - On Abscess of the Larynx Simulating Croup.

PMID- 29640941
TI  - Army Medical Department.

PMID- 29640942
TI  - Army Medical School.

PMID- 29640943
TI  - Little on the Use of Digitalis in the Failing Heart and Delirium of Acute
      Diseases.

PMID- 29640944
TI  - In-Fleshed Toe-Nail.

PMID- 29640945
TI  - Resina Copaibae as a Diuretic (Lancet, 22d March 1873).

PMID- 29640946
TI  - Action of Cold Water on the Spleen.

PMID- 29640947
TI  - On Chronic Poisoning with Chloral Hydrate.

PMID- 29640948
TI  - Siredey and Cordiner on the Treatment of Anasarca, Ascites, and Obstinate
      Pleuritic Effusions by Milk.

PMID- 29640949
TI  - The Early Symptoms and Treatment of Insanity.

PMID- 29640951
TI  - Emetics and Nauseants.

PMID- 29640950
TI  - Cerebral Haemorrhage Mistaken for Hysteria.

PMID- 29640952
TI  - A Rare Case of Restitution of the Membrana Tympani after Fifteen Years of
      Disease.

PMID- 29640953
TI  - Professor Gairdner's Lecture on Criminal Insanity.

PMID- 29640954
TI  - Army Medical Warrant.

PMID- 29640955
TI  - Isnard on the Treatment of Constipation by Arsenic.

PMID- 29640957
TI  - On Septicaemia: A Record of Investigations Made by Dr Gesualdo Clementi and Dr
      George Thin, in the Institute for Experimental Pathology, Vienna.

PMID- 29640956
TI  - Remarks on Insanity.

PMID- 29640958
TI  - Some Remarks on the History and Origin of Syphilis.

PMID- 29640959
TI  - Diarrhoea in Teething.

PMID- 29640960
TI  - Embolism in Endocarditis.

PMID- 29640961
TI  - Note of a Case of Secondary Syphilis Communicated by an Infant to Its Nurse.

PMID- 29640962
TI  - Internal Fracture of the Skull, with Puncture of the Brain.

PMID- 29640963
TI  - Digitalis an Anaphrodisiac.

PMID- 29640964
TI  - Morisonian Lectures.

PMID- 29640965
TI  - Fuming Nitric Acid for Internal Piles.

PMID- 29640966
TI  - Notes of a Case of Laceration of the Urethra with Haemorrhage into the Bladder,
      from Direct Injury.

PMID- 29640967
TI  - Notes of Practice and Peculiarities in Treatment in the New York Charity
      Hospital.

PMID- 29640968
TI  - Puerperal Tetanus.

PMID- 29640969
TI  - Podolinski on the Expulsion of Carbonic Oxide and Nitric Oxide from the Blood.

PMID- 29640970
TI  - The Medical Act Amendent Bill.

PMID- 29640971
TI  - Meetings of Societies.

PMID- 29640972
TI  - The Pulvis Glycyrrhizae Compositus.

PMID- 29640973
TI  - Difference of Longitude.

PMID- 29640975
TI  - Nephrotomy.

PMID- 29640974
TI  - Poisonous Doses of Chloral.

PMID- 29640977
TI  - Hypodermic Atropia in Cholera.

PMID- 29640976
TI  - Metallic Catheter Broken in the Urethra.

PMID- 29640978
TI  - Acute Periostitis and Subsequent Removal of the Whole Clavicle.

PMID- 29640979
TI  - Correspondence.

PMID- 29640980
TI  - On the Mechanism of Arrestment of Haemorrhage in Cases of Placenta Praevia.

PMID- 29640981
TI  - Medical News.

PMID- 29640982
TI  - Meetings of Societies.

PMID- 29640983
TI  - Some Reforms in Surgical Statistics.

PMID- 29640984
TI  - Introductory Address Delivered at the Opening of the Edinburgh Medical School on
      3d November 1873.

PMID- 29640985
TI  - Bromide of Calcium in the Treatment of Syphilitic Neuralgia.

PMID- 29640987
TI  - Resection of Coccyx to Facilitate the Formation of an Anus in the Perineum in
      Cases of Imperforate Rectum.

PMID- 29640986
TI  - Remarks on the Employment of Bulbous Bougies.

PMID- 29640988
TI  - Dermatology.-Scleroderma.

PMID- 29640989
TI  - The Saccharifying Influence of Infants' Saliva (Schiffer).

PMID- 29640990
TI  - Surgical Treatment of Ozaena.

PMID- 29640992
TI  - Accidental Poisoning by Carbolic Acid.

PMID- 29640991
TI  - On Relapsing Fever; with Special Relation to the Epidemic in Bradford in 1869-70.

PMID- 29640993
TI  - Fracture of the Skull, with Chronic Abscess-Death in Three Months.

PMID- 29640994
TI  - Special Clinical Meeting.

PMID- 29640995
TI  - Oxygen-Want: Its Causes, Signs, and Treatment.

PMID- 29640996
TI  - Note on Sthenic Dyspepsia-"Hyperchlorhydria".

PMID- 29640998
TI  - Lateral Dislocation in the Lumbar Spine.

PMID- 29640997
TI  - Passage of Latchkey through the Intestinal Canal.

PMID- 29640999
TI  - The Protection of Mankind against Tuberculosis: Being an Address before the
      Medico-Chirurgical Society of Edinburgh.

PMID- 29641000
TI  - Notes.

PMID- 29641002
TI  - Some Factors Modifying the Nutrition of Children: A Survey of 3000 of the Most
      Marked Cases of Malnutrition in Viennese Children, Made in the Summer of 1921.

PMID- 29641001
TI  - Variola in Baghdad: Notes Regarding the 168 Civilian Cases of Variola Admitted to
      the Civil Isolation Hospital, Baghdad, during the Autumn Epidemic of 1921.

PMID- 29641003
TI  - Observations on Spinal Anaesthesia.

PMID- 29641005
TI  - The Plastic Surgery of the Nose.

PMID- 29641004
TI  - On the Significance of Pyuria in Children.

PMID- 29641006
TI  - The Therapeutic Value of Quinidine Sulphate in Auricular Fibrillation.

PMID- 29641007
TI  - Notes.

PMID- 29641008
TI  - Observations on the Action of Quinidine Sulphate on Three Cases of Auricular
      Fibrillation.

PMID- 29641009
TI  - Observations on Spinal Anaesthesia.

PMID- 29641010
TI  - Letter from Vienna.

PMID- 29641011
TI  - The Urethroscope as an Aid in the Diagnosis and Treatment of Gonorrhoea.

PMID- 29641012
TI  - Private Business.

PMID- 29641013
TI  - Congenital Hyperkeratosis.

PMID- 29641014
TI  - The Father of Ovariotomy.

PMID- 29641015
TI  - The Pathological and Clinical Aspects of Deaf-Mutes.

PMID- 29641016
TI  - Methods for the Therapeutic Administration of Oxygen.

PMID- 29641017
TI  - Scottish Society of Anaesthetists.

PMID- 29641018
TI  - Letter from Vienna.

PMID- 29641019
TI  - OEsophageal Achalasia.

PMID- 29641020
TI  - Oxygen-Want: Its Causes, Signs, and Treatment.

PMID- 29641021
TI  - Early Anatomical Instruction at Edinburgh.

PMID- 29641022
TI  - The Choice of Methods Employed in the Surgical Diagnosis of Renal Disease.

PMID- 29641023
TI  - Chronic Interstitial Nephritis in Childhood: Renal Infantilism(?): A Clinical
      Record with Post-Mortem Report.

PMID- 29641024
TI  - A Case of Solitary Cyst in the Humerus.

PMID- 29641025
TI  - An Old-Time Reminiscence of Trench Foot: Crimea, 1854-55.

PMID- 29641026
TI  - Letter from Vienna.

PMID- 29641028
TI  - Notes.

PMID- 29641027
TI  - Notes.

PMID- 29641029
TI  - A Case of Myositis Ossificans Progressiva in a Child.

PMID- 29641030
TI  - The Urethroscope as an Aid in the Diagnosis and Treatment of Gonorrhoea.

PMID- 29641031
TI  - A Case of Congenital Narrowing of the OEsophagus.

PMID- 29641032
TI  - The Treatment of Disabilities of the Hand and Wrist: An Anatomical Review in
      Relation to Function.

PMID- 29641033
TI  - The Medical Curriculum.

PMID- 29641034
TI  - Aortitis, with Special Reference to Syphilitic Aortitis.

PMID- 29641035
TI  - Variations in Respiratory Exchange with Masks of Different Types.

PMID- 29641036
TI  - Special Clinical Meeting.

PMID- 29641038
TI  - Ova of Oxyuris in the Appendix.

PMID- 29641039
TI  - Ulcerative Aortitis.

PMID- 29641037
TI  - An Alternative Method of Administering Vaccines.

PMID- 29641041
TI  - Stomach in Inguinal Hernia.

PMID- 29641040
TI  - An Eighteenth Century Neurologist.

PMID- 29641042
TI  - Morison Lectures on "Mental Invalids"-II.

PMID- 29641044
TI  - An Eighteenth Century Consultant.

PMID- 29641043
TI  - The Effect of Anti-Scarlatinal Serum in a Case of Erythema Nodosum.

PMID- 29641045
TI  - Van Den Bergh's Test in Jaundice.

PMID- 29641046
TI  - Arteriosclerosis and Diabetes.

PMID- 29641047
TI  - Sources of Joint Strength.

PMID- 29641048
TI  - Treatment of Exophthalmic Goitre.

PMID- 29641049
TI  - A Note upon Twenty Cases Treated with Peptone.

PMID- 29641050
TI  - Schistoglossus and Double Tongue.

PMID- 29641052
TI  - The Diagnosis of Gall-Stone Ileus.

PMID- 29641051
TI  - The Oculo-Cardiac Reflex and Endocrinology.

PMID- 29641053
TI  - Coronary Sclerosis.

PMID- 29641054
TI  - Post-Operative Treatment of Resection of the Colon.

PMID- 29641055
TI  - Imperfectly Descended Testis.

PMID- 29641057
TI  - Notes.

PMID- 29641058
TI  - Cases of Congenital Cardiac Defect in Children.

PMID- 29641056
TI  - Solitary Non-Parasitic Cysts of the Liver.

PMID- 29641060
TI  - Neurasthenia and the Spring.

PMID- 29641059
TI  - A Study of Tuberculosis in Childhood, Based upon a Review of Forty-Two Post
      Mortem Cases.

PMID- 29641061
TI  - Cyst of the Vomeronasal Organ.

PMID- 29641062
TI  - Notes.

PMID- 29641063
TI  - Renal Decapsulation for Nephritis.

PMID- 29641064
TI  - Further Note on a Case of Adenoma of the Bile Ducts.

PMID- 29641065
TI  - Ruptured Aneurysms of the Abdominal Aorta Due to Tuberculosis: A Report of Two
      Cases.

PMID- 29641066
TI  - The Treatment of Spastic Paralysis by Sympathetic Ramisection.

PMID- 29641067
TI  - The Unity of Variola, Vaccinia, and Varicella.

PMID- 29641068
TI  - Regurgitation of the Vesical Contents.

PMID- 29641069
TI  - The Radical Cure of Hernia in Infants and Young Children.

PMID- 29641070
TI  - Tuberculosis.

PMID- 29641072
TI  - Some Considerations Regarding Tuberculosis Work in Edinburgh in Comparison with
      Anti-Tuberculosis Organisation in Russia.

PMID- 29641073
TI  - Thoracoplasty.

PMID- 29641071
TI  - The Direct Cultural Isolation and Early Cultural Investigation of a Series of
      Strains of Tubercle Bacilli from Tuberculous Lesions in Animals.

PMID- 29641075
TI  - Pulmonary Fibrosis-Tuberculous and Non-Tuberculous.

PMID- 29641074
TI  - Remarks upon the Problem of Tuberculosis in Cuba.

PMID- 29641076
TI  - Occlusion of the Coronary Arteries.

PMID- 29641078
TI  - Recurrence of Renal Calculi after Operation.

PMID- 29641077
TI  - Cases of Congenital Cardiac Defect in Children.

PMID- 29641079
TI  - Diabetic Surgery.

PMID- 29641080
TI  - Three Cases of Acute Perforating "Ulcer" of the Small Intestine.

PMID- 29641081
TI  - Oxygen Therapy: Indications, Principles, and Methods.

PMID- 29641082
TI  - The Treatment of Malignant Diseases by Goat Serum and Oleates.

PMID- 29641083
TI  - Endothermy in the Treatment of Carcinoma.

PMID- 29641084
TI  - Urinary Obstruction in Children.

PMID- 29641085
TI  - The Late Results in a Series of Forty-Nine Cases of Perforated Gastric and
      Duodenal Ulcers.

PMID- 29641087
TI  - Notes.

PMID- 29641086
TI  - Xanthomatosis: Some Aspects of Its Blood Chemistry and Pathology.

PMID- 29641088
TI  - Cancer of the Mouth.

PMID- 29641089
TI  - Congenital Stenosis of the Pylorus.

PMID- 29641090
TI  - Congenital Microcolon.

PMID- 29641091
TI  - Amount of Opium Required for Legitimate Medical Purposes.

PMID- 29641092
TI  - An Experimental Study of the Streptococci Found in Pyorrhoea Alveolaris.

PMID- 29641093
TI  - Tuberculosis of the Thyroid.

PMID- 29641094
TI  - Radiography of the Gall-Bladder.

PMID- 29641095
TI  - Fibrositis.

PMID- 29641096
TI  - Periarterial Sympathectomy.

PMID- 29641097
TI  - Morison Lectures on "Mental Invalids".

PMID- 29641098
TI  - Notes.

PMID- 29641099
TI  - Analytical Reports.

PMID- 29641100
TI  - Notes.

PMID- 29641101
TI  - The Treatment by Aspiration and Mobilisation of Traumatic Joint Effusions.

PMID- 29641102
TI  - Spontaneous Arterio-Venous Aneurysm in Thorax.

PMID- 29641103
TI  - Dr Samuel Johnson and Medicine.

PMID- 29641104
TI  - Volvulus of the Gall-Bladder.

PMID- 29641106
TI  - Analytical Note.

PMID- 29641105
TI  - Maldevelopment of the Wrist and Hand.

PMID- 29641107
TI  - Primary Carcinoma of the Gall-Bladder and Bile Ducts.

PMID- 29641108
TI  - A New Procedure in the Treatment of Bone Deformities.

PMID- 29641109
TI  - Megacolon without Constipation.

PMID- 29641110
TI  - Cases of Congenital Cardiac Defect in Children.

PMID- 29641111
TI  - Observations on the Bones in Congenital Proximal Radio-Ulnar Synostosis.

PMID- 29641112
TI  - Spontaneous Arterio-Venous Aneurysm in Thorax.

PMID- 29641113
TI  - Implantation Fibro-Adenoma.

PMID- 29641114
TI  - Notes.

PMID- 29641116
TI  - Medical Education in Scotland.

PMID- 29641115
TI  - Morison Lectures on "Mental Invalids"-I.

PMID- 29641117
TI  - Haemorrhagic Purpura.

PMID- 29641118
TI  - Tetanus Following Burn.

PMID- 29641119
TI  - Light Treatment in Tuberculous Glands.

PMID- 29641120
TI  - Treatment of Empyema by a Closed Method.

PMID- 29641121
TI  - The Development of Therapeutics.

PMID- 29641122
TI  - A Case of Cerebral Haemorrhage with Glycosuria in a Child.

PMID- 29641124
TI  - Immunity to the Pneumococcus.

PMID- 29641123
TI  - Exhibition of Patients and Specimens.

PMID- 29641126
TI  - The Milk Supply of the Country and Its Bearings on Health.

PMID- 29641125
TI  - The Role of Auto-Intoxication or Auto-Infection in the Etiology of Disease of the
      Higher and Lower Nervous System.
AB  - A hundred years ago, leading French alienists taught that mental disorders had
      their origin in abdominal disorders-cf. melancholia. This teaching has been
      largely disregarded, and never submitted to investigation from the standpoint of
      general medicine. Much attention has been drawn to the subject in the last few
      years, but the fringe of the subject has hardly yet been touched. In the last
      twenty-five years neurologists have added much information to our knowledge of
      their subject, especially the symptoms and minute anatomy of disease of the lower
      nervous system, without corresponding advance in the knowledge of etiology and
      treatment. It is necessary to take a less specialised conception of these
      disorders and investigate them from the standpoint of general medicine. (This
      conception does not invalidate the importance of the hereditary factor in
      disease.) A valuable opportunity afforded to the Edinburgh School to contribute
      its share in advancing knowledge, either by submitting fresh facts or disproving
      facts alleged by others. Reference to the author's views as published since 1900,
      dealing with the factor of auto-sepsis, taking origin in one or other of the
      mucous surfaces of the body: e.g., faulty state of teeth and gums, abnormal
      conditions of the digestive tract as revealed by (a) physical examination, (b)
      examination of stools, (c) X-rays, etc., and abnormalities in the urine, more
      especially the presence of bacteria, cells, etc. etc. The influence of auto
      sepsis in aggravating and complicating other disorders, e.g., specific infection,
      tuberculosis, etc. Reference to recent work on disseminated sclerosis and to the
      conclusions tentatively drawn by experts from it, as to the intestinal tract
      being the primary source of the toxic agent responsible for the changes in the
      nervous system. This work has been all but ignored by neurologists. Reference to
      author's experience of the common disorders of the nervous system (syphilis
      excluded), of the physical disorders present apart from the nervous system, and
      the results of treatment directed to correct these physical disorders. Criticism
      invited on the following:- 1. The need for more clinical research work on the
      subject, conducted on general rather than on "neurological" or "psychiatric"
      lines, and more especially the collection of facts dealing with the existence of
      physical disorder in disease of the central nervous system. 2. The results of
      treatment of disease of the central nervous system will be much more favourable
      if these disorders are investigated and treated on general lines than on the
      lines largely obtaining at the present time. 3. The criticism here of unwise
      specialisation in nervous disorders is equally applicable to bacteriological
      science. The outlook and practice of bacteriologists in this direction is
      unfavourable to real advance in our knowledge of the etiology and treatment of
      the disorders in question. The fault is a serious one; it applies to the system,
      not to the individual. 4. The principles contended for in the above are equally
      applicable to departments of medicine other than the "nervous" system. Lantern
      slides from Dr James Dawson's work on disseminated sclerosis, and two patients
      suffering from disseminated sclerosis to illustrate some of Dr Chalmers Watson's
      views, were shown.

PMID- 29641127
TI  - Clinical Meeting.

PMID- 29641129
TI  - Erythroedema.

PMID- 29641128
TI  - The So-Called Parkinsonian Syndrome with Special Reference to Epidemic
      Encephalitis.

PMID- 29641130
TI  - A Case of Neuroblastoma (Neurocytoma).

PMID- 29641131
TI  - Discussion on the Pituitary.

PMID- 29641132
TI  - Intracapsular Extraction of Cataract, with Cinematograph of Operation as
      Performed with Specially Designed Forceps.

PMID- 29641133
TI  - Observations on the Surgery of the Biliary Passages.

PMID- 29641135
TI  - Fibrosis of the Bronchi and Lungs in Childhood Following Bronchopneumonia.

PMID- 29641134
TI  - Clinical Meeting.

PMID- 29641136
TI  - Exhibition of Patients.

PMID- 29641137
TI  - Exhibition of Patients.

PMID- 29641138
TI  - Immunity and Sensitisation in Ringworm and Favus, and the Treatment of These
      Diseases with Vaccines.

PMID- 29641139
TI  - Presentation to Dr Irvine, Pitlochry.

PMID- 29641140
TI  - Case of Hour-Glass Relaxation, or Irregular Contraction of the Uterus.

PMID- 29641141
TI  - Case of Peritonitis from Bursting of an Abscess; with Post-Mortem Examination of
      the Body.

PMID- 29641142
TI  - Monthly Retrospect of Obstetrics and Gynaecology.

PMID- 29641143
TI  - Illustrations of a Novel and Successful Treatment of Psoriasis.

PMID- 29641144
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29641145
TI  - Trial of Chantrelle.

PMID- 29641146
TI  - Meetings of Societies.

PMID- 29641147
TI  - On the Study and Practice of Aural-Surgery: Being the Introductory Address to a
      Course of Lectures on Aural-Surgery, and of Practical Instruction in the
      Diagnosis and Treatment of the Diseases of the Ear, Given during the Summer
      Session of 1878 in the Glasgow Royal Infirmary, and in Its Medical School.

PMID- 29641149
TI  - The Sewage Question.

PMID- 29641148
TI  - Refracture for the Relief of Deformity Following Badly-Treated Fracture of the
      Extremities.

PMID- 29641150
TI  - Periscope of Otology.

PMID- 29641151
TI  - The Sewage Question.

PMID- 29641152
TI  - Case of Ascites Cured by Paracentesis and Compression.

PMID- 29641153
TI  - The Course of Diphtheria in Two Brothers Almost Simultaneously Stricken : A
      Clinical Study.

PMID- 29641154
TI  - The Comparative Merits of Animal Vaccination and Arm-To-Arm Vaccination.

PMID- 29641155
TI  - Tubercular Leprosy.

PMID- 29641156
TI  - Meetings of Societies.

PMID- 29641157
TI  - Biomineralization of Mg-Enriched Calcium Carbonates by Aerobic Microorganisms
      Enriched from Rhodoliths.
AB  - The objective of this study was to investigate the effect of Mg:Ca ratio in the
      medium on the formation of low- and high-Mg calcite by aerobic microorganisms
      enriched from rhodoliths (mainly Proteus mirabilis, Wu Do-1). XRD analyses showed
      that both low- and high-Mg calcites were formed depending on the Mg:Ca ratio in
      the medium. Calcite was formed at Ca:Mg ratios of 6:0 and 3:1 and high-Mg calcite
      was formed at Ca:Mg ratios of 1:1 and 1:3 in the medium. Huntite was formed with
      a Ca:Mg ratio of 0:6. SEM-EDS analyses showed that the low- and high-Mg calcite
      crystals had a rhombohedron shape and consisted of Ca, Si and Mg with
      extracellular polymeric substances (EPS). These results indicate that Wu Do-1
      induced precipitation of low- and high-Mg calcite crystals depending on the Ca:Mg
      ratio in the medium. The carbonate minerals were precipitated on the cell walls
      and EPS via the accumulation of Ca and/or Mg ions. Therefore, microbial formation
      of carbonate minerals may play an important role in Ca, Mg, and carbon
      biogeochemistry as well as CO2 fixation in the natural environments.

PMID- 29641158
TI  - Optimization of Electropolishing on NiTi Alloy Stents and Its Influence on
      Corrosion Behavior.
AB  - Nitinol or NiTi alloys are well-known as an attractive biomedical material due to
      their unique properties such as the shape memory effect, super-elasticity and
      biocompatibility. These characteristics enable them to be best candidates for
      implant materials such as stent. One of the major factors that strongly affect
      the performance of nitinol stent is its unique surface properties. In this study,
      the influence of electropolishing on nitinol stents and its corrosion behavior
      were observed. Electropolishing is an effective method for surface treatment,
      which not only controls the surface state but also helps to produce uniform
      surface layers. Therefore, to improve the surface quality of nitinol stents, we
      conducted an electropolishing under various conditions from 30-40 V and 10-30 s
      as a post heat treatment for nitinol stent manufacturing process. In order to
      find the optimal surface state of NiTi stents, various electropolished samples
      were explored using various characterization techniques. Furthermore, the
      potentiodynamic polarization tests were also performed to determine the corrosion
      resistance. The electropolished nitinol stents under the condition of 40 V for 10
      s exhibited the best corrosion performance as well as surface quality.

PMID- 29641159
TI  - Capmul MCM/Solutol HS15-Based Microemulsion for Enhanced Oral Bioavailability of
      Rebamipide.
AB  - Rebamipide (RBP) is a potent anti-ulcer and anti-oxidative agent, which is a BCS
      class IV drug with a low oral bioavailability of less than 10%. Thus, the
      systemic absorption of RBP into the blood circulation is an essential
      prerequisite for exerting its pharmacological activities after oral dosing.
      Herein, we report on microemulsion (ME) systems for the enhancement of oral RBP
      bioavailability. In this study, MEs consisting of Capmul MCM (oil), Solutol HS15
      (surfactant), and ethanol (co-surfactant) were prepared by the construction of
      pseudo-ternary phase diagram. The RBP-loaded MEs had spherical nano-sized
      droplets with narrow size distribution and neutral zeta potential. Moreover, the
      prepared MEs significantly enhanced the dissolution and oral bioavailability of
      RBP with no discernible intestinal toxicity. These results suggest that the
      present ME system could be further developed as an alternative oral formulation
      for RBP.

PMID- 29641160
TI  - Aripiprazole Nanocrystal Impregnated Buccoadhesive Films for Schizophrenia.
AB  - Aripiprazole is an atypical antipsychotic drug approved worldwide for treatment
      of acute and long term schizophrenia in adults. Increasingly atypical
      antipsychotics are playing a key role in the management of schizophrenia. The aim
      of the present study was to design a mucoadhesive dosage form for buccal delivery
      of aripiprazole which could provide a rapid drug delivery to the systemic
      circulation. Nanocrystals of aripiprazole were prepared by nano-precipitation
      using acid-base neutralization. These nanocrystals were then incorporated into
      buccoadhesive chitosan films. All the drug loaded films were found to smooth, non
      tacky possessing high mechanical strength. Films were characterized for
      crystallinity of drug, surface pH, thickness, folding endurance, swelling
      behavior, mucoadhesive strength, drug release and ex-vivo permeation across
      rabbit cheek mucosa. In-vitro drug release studies indicated distinctly higher
      drug release from nanocrystal loaded films, FAPZ 13 and FAPZ 14. Permeation
      studies indicated a higher flux from films FAPZ 14 (442.34 +/- 51.08 MUg/cm2/h, P
      < 0.0001) when compared to film FAPZ 12. These promising results indicate that
      the developed nanocrystal loaded buccal films FAPZ 14 have the potential to
      provide a faster availability of aripiprazole and the buccoadhesive films offer
      promising option to patients with schizophrenia especially for geriatric
      patients.

PMID- 29641161
TI  - RGD Conjugated Dendritic Polylysine for Cellular Delivery of Antisense
      Oligonucleotide.
AB  - Dendritic polylysines (DPL) are highly branched nano-sized spherical polymer with
      positively charged primary amino groups on surface. This structural feature is
      useful for a delivery of antisense oligonucleotide or siRNA. In this study, we
      modified the surface of DPL with cyclic RGD (and iRGD) peptide by conjugation
      reaction generating RGD (and iRGD) peptide conjugated dendritic poly-lysines, RGD
      DPL or iRGD-DPL. The prepared conjugates were evaluated for integrin receptor
      mediated cellular delivery of antisense oligonucleotide. The conjugation of RGD
      or iRGD peptide on DPL was monitored by measuring the retention time in capillary
      zone electrophoresis and the absorbance at UV-Vis spectroscopy. Cellular delivery
      by DPL-RGD (or -iRGD)/antisense oligonucleotide complex was examined by antisense
      splicing correction assay on integrin alpha v/beta 3 positive A375B3-Luc cells,
      which were stably transfected with plasmid pLuc/705. DPL-RGD (or -iRGD)/antisense
      oligonucleotide complexes exhibited integrin receptor mediated uptake on A375B3
      cells without inducing cellular toxicity. In addition, the delivery of antisense
      oligonucleotide was integrin receptor-dependent with moderate efficiency.

PMID- 29641162
TI  - CONSUMER EXPECTATION ON SERVICE QUALITY PROVIDE BY PHARMACIST IN SELF MEDICATION
      PRACTICES AND ITS ASSOCIATED FACTORS IN BANDUNG, INDONESIA.
AB  - Self-medication is the use of medicines for therapeutic intent without
      aclinician's advice or prescription. The National Socioeconomic Survey for
      Indonesiain 2009 found the percentage of the Indonesians engaging in self
      medicationis increasing. The objectives of this study were to assess consumers'
      expectationsregarding service quality provide by pharmacist in self-medication
      practices anddetermine the factors associated with self-medication in Bandung,
      Indonesia. Weconduct a cross-sectional survey at eight randomly selected
      community pharmaciesduring July-November 2012 and purposely sampled 1,200
      costumers purchasingmedication at those sites. Subjects reported they understood
      the informationabout the medicines given by the pharmacist but still wanted more
      informationand time to consult with the pharmacist about their medicines. Factors
      associatedwith self-medication were younger age, male gender, greater education
      andlower income. The intervention is needed to improve appropriate self
      medication.

PMID- 29641163
TI  - ON THE PRESENCE OF A TAENIA SAGINATA-LIKE PARASITE IN A TODDLER IN THAILAND.

PMID- 29641164
TI  - PERSONALITY TRAITS AND STRESS LEVELS AMONG SENIOR DENTAL STUDENTS: EVIDENCE FROM
      MALAYSIA AND SINGAPORE.
AB  - This study aimed to evaluate the association between dental students'personality
      traits and stress levels in relation to dental education programs amongsenior
      dental students in University Malaya (UM) in Malaysia and National Universityof
      Singapore (NUS). A cross-sectional survey using a self-administeredquestionnaire
      was conducted on UM and NUS senior dental students. The questionnairecomprised
      items on demographic background, the Big Five InventoryPersonality Traits (BFIPT)
      test and a modified Dental Environment Stress (DES)scale. Rasch analysis was used
      to convert raw data to interval scores. Analyseswere done by t-test, Pearson
      correlation, and Hierarchical regression statistics.The response rate was 100%
      (UM=132, NUS=76). Personality trait Agreeableness(mean=0.30) was significantly
      more prevalent among UM than NUS students(mean=0.15, p=0.016). In NUS,
      Neuroticism (mean=0.36) was significantly moreprevalent than in UM (mean=0.14,
      p=0.002). The DES mean score was higheramong NUS (mean=0.23) than UM students
      (mean=0.07). In UM, Neuroticismwas significantly correlated with stress levels
      (r=0.338, p<0.001). In NUS, thesewere Neuroticism (r=0.278, p=0.015),
      Agreeableness (r=0.250, p=0.029) and Conscientiousness(r=-0.242, p=0.035)
      personality traits. The correlation was strongestfor personality trait
      Neuroticism in both schools. Hierarchical regression analysisshowed that gender
      and Neuroticism were significant predictors for students'stress levels (p<0.05)
      with the latter exerting a bigger effect size (R2=0.18) thangender (R2=004). This
      study showed that gender and Neuroticism personalitytrait were significant
      predictors for stress levels among selected groups of dentalstudents in Southeast
      Asia. Information on students' personality may be useful innew students' intake,
      stress management counseling and future program reviews.

PMID- 29641165
TI  - PRSS1 and SPINK1 Mutations in Alcoholic and Idiopathic Chronic Pancreatitis.
AB  - Several recent studies have reported associations between gene mutations and
      chronic pancreatitis (CP); however, little is known about their association with
      risk of CP in the Chinese Han population. The aim of this study was to describe
      mutations in the cationic trypsinogen (PRSS1) and serine protease inhibitor Kazal
      type 1 (SPINK1) genes in patients with alcoholic chronic pancreatitis (ACP) and
      idiopathic chronic pancreatitis (ICP) and to investigate their influence on the
      clinical course of the disease. One hundred patients (24 with ACP, 76 with ICP)
      and 100 healthy volunteers (control group) were enrolled in the study. PRSS1
      (R122H) mutations were detected in one (1.3%) patient with ICP and SPINK1 (N34S)
      mutations were present in one (4.1%) patient with ACP. PRSS1 and SPINK1 mutations
      were not detected in the control populations. There were no statistically
      significant differences between the CP patients and the control group. Those
      preliminary data suggest low prevalence of SPINK1 and PRSS1 mutations in the
      Chinese population, generally, as well as in CP patients, indicating that these
      mutations do not contribute to the development of CP.

PMID- 29641166
TI  - Nanoemulsion-Based Hydrogel for Topical Delivery of Highly Skin-Permeable Growth
      Factor Combinations: Preparation and In Vitro Evaluation.
AB  - Topical administration of growth factors has been suggested as a promising
      strategy for promoting the healing process and skin regeneration in wound
      management. However, several restrictions hinder their successful clinical use;
      specifically, limited percutaneous absorption causes inconsistent efficacy, and
      various growth factors with specific functionalities are required at different
      stages of healing. To overcome these shortcomings, previously we have constructed
      highly skin-permeable analogues of epidermal growth factor (EGF), insulin-like
      growth factor-I (IGF-I), and platelet-derived growth factor-A (PDGF-A) (LMWP-EGF,
      LMWP-IGF-I and LMWP-PDGF-A) by genetically conjugating the low-molecular-weight
      protamine (LMWP) to their N-terminus. In the present study, we determined the
      optimal concentration ratio of these growth factors by investigating In Vitro
      cell proliferation and the scratch wound repairing assay. After confirming
      synergetic effects of growth factors in combinations, we developed a topical
      delivery system consisting of a nanoemulsion (NE)-dispersed polyvinylpyrrolidone
      hydrogel loaded with all three growth factors. In Vitro permeability studies were
      also performed to assess whether the LMWP-conjugated growth factors in the
      formulation enhanced their skin permeation compared to native growth factors.
      Combinations of native or LMWP-fused growth factors significantly promoted
      fibroblast proliferation and scratch wound recovery, and the synergy of LMWP-EGF,
      LMWP-IGF-I and LMWP-PDGF-A was optimal at a ratio of 100:100:10 by concentration.
      The growth factor combination-loaded NE appeared to be spherical under cryo
      transmission electron microscopy and the average droplet diameter was 127+/-4.30
      nm. The LMWP-conjugated growth factors allowed significantly higher skin
      permeation than native growth factors from the NE-dispersed hydrogel. Thus, the
      LMWP-conjugated growth factor combination-loaded NE-dispersed hydrogel is
      expected to induce more rapid and prolonged wound healing.

PMID- 29641168
TI  - Crystallographic Trapping of Reaction Intermediates in Quinolinic Acid Synthesis
      by NadA.
AB  - NadA is a multifunctional enzyme that condenses dihydroxyacetone phosphate (DHAP)
      with iminoaspartate (IA) to generate quinolinic acid (QA), the universal
      precursor of the nicotinamide adenine dinucleotide (NAD(P)) cofactor. Using X-ray
      crystallography, we have (i) characterized two of the reaction intermediates of
      QA synthesis using a "pH-shift" approach and a slowly reacting Thermotoga
      maritima NadA variant and (ii) observed the QA product, resulting from the
      degradation of an intermediate analogue, bound close to the entrance of a long
      tunnel leading to the solvent medium. We have also used molecular docking to
      propose a condensation mechanism between DHAP and IA based on two previously
      published Pyrococcus horikoshi NadA structures. The combination of reported data
      and our new results provide a structure-based complete catalytic sequence of QA
      synthesis by NadA.

PMID- 29641167
TI  - Development of Polyethylene Glycol-Conjugated Chitosan Oligosaccharide Derivative
      Stabilized Gold Nanoassemblies.

PMID- 29641169
TI  - Self-Assembled Rose Bengal-Exopolysaccharide Nanoparticles for Improved
      Photodynamic Inactivation of Bacteria by Enhancing Singlet Oxygen Generation
      Directly in the Solution.
AB  - It is of great value to develop new antibacterial photodynamic therapy (PDT)
      strategies to improve antibacterial PDT efficacy of noncationic photosensitizers
      without introducing cytotoxicity, which is a great challenge for current leading
      efforts on antimicrobial PDT based on cell surface engineering. In this research,
      the hydrophobic and anionic photosensitizer rose bengal (RB) was chemically
      conjugated with bacterial exopolysaccharide (EPS) to generate an amphiphilic and
      negatively charged compound EPS-RB that could self-assemble into nanoparticles
      (NPs) in solution. These EPS-RB NPs possessed an increased singlet oxygen
      generation property in solution. As a result, EPS-RB exhibited improved
      photoinactivation for both Gram-negative and Gram-positive bacteria, leading to a
      record low RB working concentration, 8 MUM or 500 nM for Escherichia coli or
      Staphylococcus aureus, respectively. Upon light irradiation, more EPS-RB bound to
      the cell surface and penetrated into bacteria than RB, with EPS-RB staying around
      the cell surface of the most irradiated E. coli while entering all irradiated S.
      aureus. Both scanning electron microscopy and fluorescence confocal imaging
      results show that the cell membrane of E. coli was damaged heavily but not S.
      aureus. All of these observations indicate that both the enhanced singlet oxygen
      production of EPS-RB NPs in solution and their consequently increased membrane
      binding and cellular penetration into the bacteria through the damaged cell
      membrane contribute to their significantly improved bacterial photoinactivation
      efficiency. In addition, EPS-RB has low cytotoxicity and negligible hemolytic
      activity, showing great biocompatibility. Therefore, the construction of EPS-RB
      provides a new strategy for the PDT effectiveness improvement of the separated
      cell/sensitizer systems and thus the design of next-generation antimicrobial
      agents.

PMID- 29641171
TI  - Chemiresistive Graphene Sensors for Ammonia Detection.
AB  - The primary objective of this work is to demonstrate a novel sensor system as a
      convenient vehicle for scaled-up repeatability and the kinetic analysis of a
      pixelated testbed. This work presents a sensor system capable of measuring
      hundreds of functionalized graphene sensors in a rapid and convenient fashion.
      The sensor system makes use of a novel array architecture requiring only one
      sensor per pixel and no selector transistor. The sensor system is employed
      specifically for the evaluation of Co(tpfpp)ClO4 functionalization of graphene
      sensors for the detection of ammonia as an extension of previous work.
      Co(tpfpp)ClO4 treated graphene sensors were found to provide 4-fold increased
      ammonia sensitivity over pristine graphene sensors. Sensors were also found to
      exhibit excellent selectivity over interfering compounds such as water and common
      organic solvents. The ability to monitor a large sensor array with 160 pixels
      provides insights into performance variations and reproducibility-critical
      factors in the development of practical sensor systems. All sensors exhibit the
      same linearly related responses with variations in response exhibiting Gaussian
      distributions, a key finding for variation modeling and quality engineering
      purposes. The mean correlation coefficient between sensor responses was found to
      be 0.999 indicating highly consistent sensor responses and excellent
      reproducibility of Co(tpfpp)ClO4 functionalization. A detailed kinetic model is
      developed to describe sensor response profiles. The model consists of two
      adsorption mechanisms-one reversible and one irreversible-and is shown capable of
      fitting experimental data with a mean percent error of 0.01%.

PMID- 29641170
TI  - Ultrasmall TiO2-Coated Reduced Graphene Oxide Composite as a High-Rate and Long
      Cycle-Life Anode Material for Sodium-Ion Batteries.
AB  - Because of the low cost and abundant nature of the sodium element, sodium-ion
      batteries (SIBs) are attracting extensive attention, and a variety of SIB cathode
      materials have been discovered. However, the lack of high-performance anode
      materials is a major challenge of SIBs. Herein, we have synthesized ultrasmall
      TiO2-nanoparticle-coated reduced graphene oxide (TiO2@RGO) composites by using a
      one-pot hydrolysis method, which are then investigated as anode materials for
      SIBs. The morphology of TiO2@RGO has been characterized using transmission
      electron microscopy, indicating that the TiO2 nanospheres uniformly grow on the
      surface of the RGO nanosheet. As-prepared TiO2@RGO composites exhibited a
      promising electrochemical performance in terms of cycling stability and rate
      capability, especially the initial cycle Coulombic efficiency of 60.7%, which is
      higher than that in previous reports. The kinetics of the electrode reaction has
      been investigated by cyclic voltammetry. The results indicate that the sodium-ion
      intercalation/extraction behavior is not controlled by the semiinfinite diffusion
      process, which gives rise to an outstanding rate performance. In addition, the
      electrochemical performance of TiO2@RGO composites in full cells, coupled with
      carbon-coated Na3V2(PO4)3 as the positive material, has been investigated. The
      discharge specific capacity was up to 117.2 mAh g-1, and it remained at 84.6 mAh
      g-1 after 500 cycles under a current density of 2 A g-1, which shows excellent
      cycling stability.

PMID- 29641172
TI  - Hierarchical and Well-Ordered Porous Copper for Liquid Transport Properties
      Control.
AB  - Liquid delivery through interconnected pore network is essential for various
      interfacial transport applications ranging from energy storage to evaporative
      cooling. The liquid transport performance in porous media can be significantly
      improved through the use of hierarchical morphology that leverages transport
      phenomena at different length scales. Traditional surface engineering techniques
      using chemical or thermal reactions often show nonuniform surface nanostructuring
      within three-dimensional pore network due to uncontrollable diffusion and
      reactivity in geometrically complex porous structures. Here, we demonstrate
      hierarchical architectures on the basis of crystalline copper inverse opals using
      an electrochemistry approach, which offers volumetric controllability of
      structural and surface properties within the complex porous metal. The
      electrochemical process sequentially combines subtractive and additive steps
      electrochemical polishing and electrochemical oxidation-to improve surface
      wetting properties without sacrificing structural permeability. We report the
      transport performance of the hierarchical inverse opals by measuring the
      capillary-driven liquid rise. The capillary performance parameter of
      hierarchically engineered inverse opal ( K/ Reff = ~5 * 10-3 MUm) is shown to be
      higher than that of a typical crystalline inverse opal ( K/ Reff = ~1 * 10-3 MUm)
      owing to the enhancement in fluid permeable and hydrophilic pathways. The new
      surface engineering method presented in this work provides a rational approach in
      designing hierarchical porous copper for transport performance enhancements.

PMID- 29641173
TI  - Monodisperse Metal-Organic Framework Nanospheres with Encapsulated Core-Shell
      Nanoparticles Pt/Au@Pd@{Co2(oba)4(3-bpdh)2}4H2O for the Highly Selective
      Conversion of CO2 to CO.
AB  - A new microporous metal-organic framework (MOF) with formula {Co2(oba)4(3
      bpdh)2}4H2O [oba = 4,4'-oxybis(benzoic acid); 3-bpdh = N, N'-bis-(1-pyridine-3-yl
      ethylidene)-hydrazine] was assembled, and its morphology was found to undergo a
      microrod-to-nanosphere transformation with temperature variation. Core-shell
      Au@Pd functional nanoparticles (NPs) were successfully encapsulated in the center
      of the monodisperse nanospheres, and Pt NPs were well-dispersed and fully
      immobilized on the surface of Au@Pd@1Co to build the Pt/Au@Pd@1Co composites,
      which exhibited NPs catalytic activity for the reverse water gas shift reaction.
      The core-shell Au@Pd NPs in MOF significantly enchanced the CO selectivity of the
      catalyst, and the Pt NP loading on the surface of the nanosphere afforded a
      desirable CO2 conversion.

PMID- 29641174
TI  - Electrodeposited Ni-Based Magnetic Mesoporous Films as Smart Surfaces for Atomic
      Layer Deposition: An "All-Chemical" Deposition Approach toward 3D Nanoengineered
      Composite Layers.
AB  - Mesoporous Ni and Cu-Ni (Cu20Ni80 and Cu45Ni55 in at. %) films, showing a three
      dimensional (3D) porous structure and tunable magnetic properties, are prepared
      by electrodeposition from aqueous surfactant solutions using micelles of P-123
      triblock copolymer as structure-directing entities. Pores between 5 and 30 nm and
      dissimilar space arrangements (continuous interconnected networks, circular
      pores, corrugated mesophases) are obtained depending on the synthetic conditions.
      X-ray diffraction studies reveal that the Cu-Ni films have crystallized in the
      face-centered cubic structure, are textured, and exhibit certain degree of phase
      separation, particularly those with a higher Cu content. Atomic layer deposition
      (ALD) is used to conformally coat the mesopores of Cu20Ni80 film with amorphous
      Al2O3, rendering multiphase "nano-in-meso" metal-ceramic composites without
      compromising the ferromagnetic response of the metallic scaffold. From a
      technological viewpoint, these 3D nanoengineered composite films could be
      appealing for applications like magnetically actuated micro/nanoelectromechanical
      systems (MEMS/NEMS), voltage-driven magneto-electric devices, capacitors, or as
      protective coatings with superior strength and tribological performance.

PMID- 29641175
TI  - New Dopamine D2 Receptor Agonist, [3H]MCL-536, for Detecting Dopamine D2high
      Receptors in Vivo.
AB  - Increases in the D2 receptor high affinity state are associated with certain
      neurological disorders. We synthesized and characterized the high-affinity D2high
      ligand [3H]MCL-536 in competition binding against the D2/3 agonist R-(-)- N- n
      propylnorapomorphine (NPA) and the D2/3 antagonist raclopride. The total binding
      of [3H]MCL-536 (minus that in the presence of 100 nM NPA) was measured by
      saturation binding in CHO cells expressing human D2long; the data yielded
      separable, nonsaturable nonspecific, and saturable specific components. The
      former represents an aporphine site common to NPA and [3H]MCL-536. The latter
      indicated specific binding to the total D2 receptors (both high and low-affinity
      states). [3H]MCL-536 had a Kd of 0.8 nM. In competition binding, NPA had a Ki of
      0.16 nM, and raclopride had a Ki of 0.9 nM. Co-incubation with
      guanylylimidodiphosphate abolished binding to D2high. This unique profile makes
      radiolabeled MCL-536 a versatile tool for diagnostics and therapeutics, and may
      quantify D2high sites in schizophrenia and PD patients in vivo.

PMID- 29641176
TI  - Formation of Lead Halide Perovskite Based Plasmonic Nanolasers and Nanolaser
      Arrays by Tailoring the Substrate.
AB  - Hybrid plasmonic nanolasers are intensively studied due to their nanoscale mode
      confinement and potentials in highly integrated photonic and quantum devices.
      Until now, the characteristics of plasmonic nanolasers are mostly determined by
      the crystal facets of top semiconductors, such as ZnO nanowires or nanoplates. As
      a result, the spasers are isolated, and their lasing wavelengths are random and
      difficult to tune. Herein, we experimentally demonstrate the formation of lead
      halide perovskite (MAPbX3) based hybrid plasmonic nanolasers and nanolaser arrays
      with arbitrary cavity shapes and controllable lasing wavelengths. These spasers
      are composed of MAPbX3 perovskite nanosheets, which are separated from Au
      patterns with a 10 nm SiO2 spacer. In contrast to previous reports, here, the
      spasers are determined by the boundary of Au patterns instead of the crystal
      facets of MAPbX3 nanosheets. As a result, whispering gallery mode based circular
      spasers and spaser arrays were successfully realized by patterning the Au
      substrate into circles and gratings, respectively. The standard wavelength
      deviation of spaser arrays is as small as 0.3 nm. Meanwhile, owing to the anion
      exchangeable property of MAPbX3 perovskite, the emission wavelengths of spasers
      were tuned more than 100 nm back and forth by changing the stoichiometry of
      perovskite postsynthetically.

PMID- 29641177
TI  - Reducing Coercive-Field Scaling in Ferroelectric Thin Films via Orientation
      Control.
AB  - The desire for low-power/voltage operation of devices is driving renewed interest
      in understanding scaling effects in ferroelectric thin films. As the dimensions
      of ferroelectrics are reduced, the properties can vary dramatically, including
      the robust scaling relationship between coercive field ( Ec) and thickness ( d),
      also referred to as the Janovec-Kay-Dunn (JKD) law, wherein Ec ? d-2/3. Here, we
      report that whereas (001)-oriented heterostructures follow JKD scaling across the
      thicknesses range of 20-330 nm, (111)-oriented heterostructures of the canonical
      tetragonal ferroelectric PbZr0.2Ti0.8O3 exhibit a deviation from JKD scaling
      wherein a smaller scaling exponent for the evolution of Ec is observed in films
      of thickness ? 165 nm. X-ray diffraction reveals that whereas (001)-oriented
      heterostructures remain tetragonal for all thicknesses, (111)-oriented
      heterostructures exhibit a transition from tetragonal-to-monoclinic symmetry in
      films of thickness ? 165 nm as a result of the compressive strain. First
      principles calculations suggest that this symmetry change contributes to the
      deviation from the expected scaling, as the monoclinic phase has a lower energy
      barrier for switching. This structural evolution also gives rise to changes in
      the c/ a lattice parameter ratio, wherein this ratio increases and decreases in
      (001)- and (111)-oriented heterostructures, respectively, as the films are made
      thinner. In (111)-oriented heterostructures, this reduced tetragonality drives a
      reduction of the remanent polarization and, therefore, a reduction of the domain
      wall energy and overall energy barrier to switching, which further exacerbates
      the deviation from the expected scaling. Overall, this work demonstrates a route
      toward reducing coercive fields in ferroelectric thin films and provides a
      possible mechanism to understand the deviation from JKD scaling.

PMID- 29641178
TI  - Encapsulating Silica/Antimony into Porous Electrospun Carbon Nanofibers with
      Robust Structure Stability for High-Efficiency Lithium Storage.
AB  - To address the volume-change-induced pulverization problems of electrode
      materials, we propose a "silica reinforcement" concept, following which silica
      reinforced carbon nanofibers with encapsulated Sb nanoparticles (denoted as
      SiO2/Sb@CNFs) are fabricated via an electrospinning method. In this composite
      structure, insulating silica fillers not only reinforce the overall structure but
      also contribute to additional lithium storage capacity; encapsulation of Sb
      nanoparticles into the carbon-silica matrices efficiently buffers the volume
      changes during Li-Sb alloying-dealloying processes upon cycling and alleviates
      the mechanical stress; the porous carbon nanofiber framework allows for fast
      charge transfer and electrolyte diffusion. These advantageous characteristics
      synergistically contribute to the superior lithium storage performance of
      SiO2/Sb@CNF electrodes, which demonstrate excellent cycling stability and rate
      capability, delivering reversible discharge capacities of 700 mA h/g at 200 mA/g,
      572 mA h/g at 500 mA/g, and 468 mA h/g at 1000 mA/g each after 400 cycles. Ex
      situ as well as in situ TEM measurements confirm that the structural integrity of
      silica-reinforced Sb@CNF electrodes can efficiently withstand the mechanical
      stress induced by the volume changes. Notably, the SiO2/Sb@CNF//LiCoO2 full cell
      delivers high reversible capacities of ~400 mA h/g after 800 cycles at 500 mA/g
      and ~336 mA h/g after 500 cycles at 1000 mA/g.

PMID- 29641179
TI  - Surface-Enhanced Molecular Electron Energy Loss Spectroscopy.
AB  - Electron energy loss spectroscopy (EELS) in a scanning transmission electron
      microscope (STEM) is becoming an important technique in spatially resolved
      spectral characterization of optical and vibrational properties of matter at the
      nanoscale. EELS has played a significant role in understanding localized
      polaritonic excitations in nanoantennas and also allows for studying molecular
      excitations in nanoconfined samples. Here we theoretically describe the
      interaction of a localized electron beam with molecule-covered polaritonic
      nanoantennas, and propose the concept of surface-enhanced molecular EELS
      exploiting the electromagnetic coupling between the nanoantenna and the molecular
      sample. Particularly, we study plasmonic and infrared phononic antennas covered
      by molecular layers, exhibiting either an excitonic or vibrational response. We
      demonstrate that EEL spectra of these molecule-antenna coupled systems exhibit
      Fano-like or strong coupling features, similar to the ones observed in far-field
      optical and infrared spectroscopy. EELS offers the advantage to acquire spectral
      information with nanoscale spatial resolution, and importantly, to control the
      antenna-molecule coupling on demand. Considering ongoing instrumental
      developments, EELS in STEM shows the potential to become a powerful tool for
      fundamental studies of molecules that are naturally or intentionally located on
      nanostructures supporting localized plasmon or phonon polaritons. Surface
      enhanced EELS might also enable STEM-EELS applications such as remote- and thus
      damage-free-sensing of the excitonic and vibrational response of molecules,
      quantum dots, or 2D materials.

PMID- 29641180
TI  - Recombinant Spider Silk Functionalized with a Motif from Fibronectin Mediates
      Cell Adhesion and Growth on Polymeric Substrates by Entrapping Cells During Self
      Assembly.
AB  - In vitro endothelialization of synthetic grafts or engineered vascular constructs
      is considered a promising alternative to overcome shortcomings in the
      availability of autologous vessels and in-graft complications with synthetics. A
      number of cell-seeding techniques have been implemented to render vascular grafts
      accessible for cells to attach, proliferate, and spread over the surface area.
      Nonetheless, seeding efficiency and the time needed for cells to adhere varies
      dramatically. Herein, we investigated a novel cell-seeding approach (denoted co
      seeding) that enables cells to bind to a motif from fibronectin included in a
      recombinant spider silk protein. Entrapment of cells occurs at the same time as
      the silk assembles into a nanofibrillar coating on various substrates. Cell
      adhesion analysis showed that the technique can markedly improve cell-seeding
      efficiency to nonfunctionalized polystyrene surfaces, as well as establish cell
      attachment and growth of human dermal microvascular endothelial cells on bare
      polyethylene terephthalate and polytetrafluoroethylene (PTFE) substrates.
      Scanning electron microscopy images revealed a uniform endothelial cell layer and
      cell-substratum compliance with the functionalized silk protein to PTFE surfaces.
      The co-seeding technique holds a great promise as a method to reliably and
      quickly cellularize engineered vascular constructs as well as to in vitro
      endothelialize commercially available cardiovascular grafts.

PMID- 29641181
TI  - O-GlcNAcase Fragment Discovery with Fluorescence Polarimetry.
AB  - The attachment of the sugar N-acetyl-D-glucosamine (GlcNAc) to specific serine
      and threonine residues on proteins is referred to as protein O-GlcNAcylation. O
      GlcNAc transferase (OGT) is the enzyme responsible for carrying out the
      modification, while O-GlcNAcase (OGA) reverses it. Protein O-GlcNAcylation has
      been implicated in a wide range of cellular processes including transcription,
      proteostasis, and stress response. Dysregulation of O-GlcNAc has been linked to
      diabetes, cancer, and neurodegenerative and cardiovascular disease. OGA has been
      proposed to be a drug target for the treatment of Alzheimer's and cardiovascular
      disease given that increased O-GlcNAc levels appear to exert a protective effect.
      The search for specific, potent, and drug-like OGA inhibitors with
      bioavailability in the brain is therefore a field of active research, requiring
      orthogonal high-throughput assay platforms. Here, we describe the synthesis of a
      novel probe for use in a fluorescence polarization based assay for the discovery
      of inhibitors of OGA. We show that the probe is suitable for use with both human
      OGA, as well as the orthologous bacterial counterpart from Clostridium
      perfringens, CpOGA, and the lysosomal hexosaminidases HexA/B. We structurally
      characterize CpOGA in complex with a ligand identified from a fragment library
      screen using this assay. The versatile synthesis procedure could be adapted for
      making fluorescent probes for the assay of other glycoside hydrolases.

PMID- 29641182
TI  - Effect of Sodium Selenate on Hippocampal Proteome of 3*Tg-AD Mice-Exploring the
      Antioxidant Dogma of Selenium against Alzheimer's Disease.
AB  - Selenium (Se), an antioxidant trace element, is an important nutrient for
      maintaining brain functions and is reported to be involved in Alzheimer's disease
      (AD) pathologies. The present study has been designed to elucidate the protein
      changes in hippocampus of 3*Tg-AD mice after supplementing sodium selenate as an
      inorganic source of selenium. By using iTRAQ proteomics technology, 113
      differentially expressed proteins (DEPs) are found in AD/WT mice with 37
      upregulated and 76 downregulated proteins. Similarly, in selenate-treated 3*Tg-AD
      (ADSe/AD) mice, 115 DEPs are found with 98 upregulated and 17 downregulated
      proteins. The third group of mice (ADSe/WT) showed 75 DEPs with 46 upregulated
      and 29 downregulated proteins. Among these results, 42 proteins (40 downregulated
      and 2 upregulated) in the diseased group showed reverse expression when treated
      with selenate. These DEPs are analyzed with different bioinformatics tools and
      are found associated with various AD pathologies and pathways. Based on their
      functions, selenate-reversed proteins are classified as structural proteins,
      metabolic proteins, calcium regulating proteins, synaptic proteins, signaling
      proteins, stress related proteins, and transport proteins. Six altered AD
      associated proteins are successfully validated by Western blot analysis. This
      study shows that sodium selenate has a profound effect on the hippocampus of the
      triple transgenic AD mice. This might be established as an effective therapeutic
      agent after further investigation.

PMID- 29641183
TI  - An Automated Design Framework for Multicellular Recombinase Logic.
AB  - Tools to systematically reprogram cellular behavior are crucial to address
      pressing challenges in manufacturing, environment, or healthcare. Recombinases
      can very efficiently encode Boolean and history-dependent logic in many species,
      yet current designs are performed on a case-by-case basis, limiting their
      scalability and requiring time-consuming optimization. Here we present an
      automated workflow for designing recombinase logic devices executing Boolean
      functions. Our theoretical framework uses a reduced library of computational
      devices distributed into different cellular subpopulations, which are then
      composed in various manners to implement all desired logic functions at the
      multicellular level. Our design platform called CALIN (Composable Asynchronous
      Logic using Integrase Networks) is broadly accessible via a web server, taking
      truth tables as inputs and providing corresponding DNA designs and sequences as
      outputs (available at http://synbio.cbs.cnrs.fr/calin ). We anticipate that this
      automated design workflow will streamline the implementation of Boolean functions
      in many organisms and for various applications.

PMID- 29641184
TI  - Access to Household Water Quality Information Leads to Safer Water: A Cluster
      Randomized Controlled Trial in india.
AB  - Household-specific feedback on the microbiological safety of drinking water may
      result in changes to water management practices that reduce exposure risks. We
      conducted a randomized, controlled trial in India to determine if information on
      household drinking water quality could change behavior and improve
      microbiological quality as indicated by Escherichia coli counts. We randomly
      assigned 589 participating households to one of three arms: (1) a messaging-only
      arm receiving messaging on safe water management ( n = 237); (2) a standard
      testing arm receiving the same messaging plus laboratory E. coli testing results
      specific to that household's drinking water ( n = 173); and (3) a test kit arm
      receiving messaging plus low-cost E. coli tests that could be used at the
      household's discretion ( n = 179). Self-reported water treatment increased
      significantly in both the standard testing arm and the test kit arm between
      baseline and follow-up one month later. Mean log10 E. coli counts per 100 mL in
      household stored drinking water increased in the messaging-only arm from 1.42 to
      1.87, while decreasing in the standard testing arm (1.38 to 0.89, 65% relative
      reduction) and the test kit arm (1.08 to 0.65, 76% relative reduction). Findings
      indicate that household-specific water quality information can improve both
      behaviors and drinking water quality.

PMID- 29641185
TI  - Toxicokinetics in Risk Evaluations.
AB  - Quantitative predictions of in vivo chemical levels based on in vitro data will
      become a cornerstone of next generation nonanimal risk evaluations. Both
      regulatory and scientific experience with quantitative toxicokinetics must
      increase now for this transition to happen.

PMID- 29641186
TI  - Spatial-Resolution Cell Type Proteome Profiling of Cancer Tissue by Fully
      Integrated Proteomics Technology.
AB  - Increasing attention has been focused on cell type proteome profiling for
      understanding the heterogeneous multicellular microenvironment in tissue samples.
      However, current cell type proteome profiling methods need large amounts of
      starting materials which preclude their application to clinical tumor specimens
      with limited access. Here, by seamlessly combining laser capture microdissection
      and integrated proteomics sample preparation technology SISPROT, specific cell
      types in tumor samples could be precisely dissected with single cell resolution
      and processed for high-sensitivity proteome profiling. Sample loss and
      contamination due to the multiple transfer steps are significantly reduced by the
      full integration and noncontact design. H&E staining dyes which are necessary for
      cell type investigation could be selectively removed by the unique two-stage
      design of the spintip device. This easy-to-use proteome profiling technology
      achieved high sensitivity with the identification of more than 500 proteins from
      only 0.1 mm2 and 10 MUm thickness colon cancer tissue section. The first cell
      type proteome profiling of four cell types from one colon tumor and surrounding
      normal tissue, including cancer cells, enterocytes, lymphocytes, and smooth
      muscle cells, was obtained. 5271, 4691, 4876, and 2140 protein groups were
      identified, respectively, from tissue section of only 5 mm2 and 10 MUm thickness.
      Furthermore, spatially resolved proteome distribution profiles of enterocytes,
      lymphocytes, and smooth muscle cells on the same tissue slices and across four
      consecutive sections with micrometer distance were successfully achieved. This
      fully integrated proteomics technology, termed LCM-SISPROT, is therefore
      promising for spatial-resolution cell type proteome profiling of tumor
      microenvironment with a minute amount of clinical starting materials.

PMID- 29641187
TI  - Artificial Mating-Type Conversion and Repetitive Mating for Polyploid Generation.
AB  - The yeast Saccharomyces cerevisiae is one of the best-understood biological
      systems and can produce numerous useful compounds. Sexual hybridization (mating)
      can drive dramatic evolution of yeasts by the inheritance of half of the parental
      genomic information from each cell. Unfortunately, half of the parental genomic
      information is lost in individual cells in the next generation. Additionally,
      recombination of homologous chromosomes during meiosis gives rise to diversity in
      the next generation; hence, it is commonly employed to identify targets from
      diverse cell populations, based on the mating machinery. Here, we established a
      system for generating polyploids that inherit all genetic information from the
      parental strains via artificial mating-type conversion and repetitive mating. We
      prepared alpha-type haploid strains whose chromosomes were tagged with genes
      encoding fluorescent proteins or transcriptional factors. Only the mating-type
      locus was successfully converted from alpha-type to a-type sequence by the
      endonuclease Ho, and the resultant a-type cells mated with each alpha-type
      haploid to yield an a/alpha-type diploid strain with all genetic information from
      both parental strains. Importantly, we repeatedly converted the mating-type of
      polyploid cells to obtain a-type cells capable of mating with alpha-type cells.
      This approach can potentially facilitate yeast-strain development with
      unparalleled versatility, utilizing vast available resources.

PMID- 29641188
TI  - Reciprocating Compression of ZnO Probed by X-ray Diffraction: The Size Effect on
      Structural Properties under High Pressure.
AB  - Zinc oxide, ZnO, an important technologically relevant binary compound, was
      investigated by reciprocating compress the sample in a diamond anvil cell using
      in situ high-pressure synchrotron X-ray diffraction at room temperature. The
      starting sample (~200 nm) was compressed to 20 GPa and then decompressed to
      ambient condition. The quenched sample, with average grain size ~10 nm, was
      recompressed to 20 GPa and then released to ambient condition. The structural
      stability and compressibility of the initial bulk ZnO and quenched nano ZnO were
      compared. Results reveal that the grain size and the fractional cell distortion
      have little effect on the structural stability of ZnO. The bulk modulus of the B4
      (hexagonal wurtzites structure) and B1 (cubic rock salt structure) phases for
      bulk ZnO under hydrostatic compression were estimated as 164(3) and 201(2) GPa,
      respectively. Importantly, the effect of pressure in atomic positions, bond
      distances, and bond angles was obtained. On the basis of this information, the B4
      to-B1 phase transformation was demonstrated to follow the hexagonal path rather
      than the tetragonal path. For the first time, the detail of the intermediate
      hexagonal ZnO, revealing the B4-to-B1 transition mechanism, was detected by
      experimental method. These findings enrich our knowledge on the diversity of the
      size influences on the high-pressure behaviors of materials and offer new
      insights into the mechanism of the B4-to-B1 phase transition that is commonly
      observed in many other wurzite semiconductor compounds.

PMID- 29641189
TI  - Enantioselective Ni-Al Bimetallic Catalyzed exo-Selective C-H Cyclization of
      Imidazoles with Alkenes.
AB  - A Ni-Al bimetallic catalyzed enantioselective C-H exo-selective cyclization of
      imidazoles with alkenes has been developed. A series of bi- or polycyclic
      imidazoles with beta-stereocenter were obtained in up to 98% yield and >99% ee.
      The bifunctional SPO ligand-promoted bimetallic catalysis proved to be critical
      to this challenging stereocontrol.

PMID- 29641191
TI  - Characterization and Use of TurboLuc Luciferase as a Reporter for High-Throughput
      Assays.
AB  - Luciferase-based reporter assays are powerful tools for monitoring gene
      expression in cells because of their ultrasensitive detection capacity and wide
      dynamic range. Here we describe the characterization and use of a luciferase
      reporter enzyme derived from the marine copepod Metridia luciferase family,
      referred to as TurboLuc luciferase (TurboLuc). To develop TurboLuc, the wild-type
      luciferase was modified to decrease its size, increase brightness, slow
      luminescent signal decay, and provide for efficient intracellular expression. To
      determine the enzyme susceptibility to compound inhibition and judge the
      suitability of using of TurboLuc as a reporter in screening assays, purified
      TurboLuc enzyme was screened for inhibitors using two different compound
      libraries. No inhibitors of this enzyme were identified in a library
      representative of typical diverse low molecular weight (LMW) compounds using a
      purified TurboLuc enzyme assay supporting that such libraries will show very low
      interference with this enzyme. We were able to identify a few inhibitors from a
      purified natural product library which can serve as useful tools to validate
      assays using TurboLuc. In addition to the inhibitor profile for TurboLuc we
      describe the use of this reporter in cells employing miniaturized assay volumes
      within 1536-well plates. TurboLuc luciferase is the smallest luciferase reporter
      enzyme described to date (16 kDa), shows bright luminescence and low interference
      by LMW compounds, and therefore should provide an ideal reporter in assays
      applied to high-throughput screening.

PMID- 29641192
TI  - Synergetic Influence of Alkali-Metal and Lone-Pair Cations on Frameworks of
      Tellurites.
AB  - Four new tellurites were hydrothermally synthesized by the adjustment of
      different alkali-metal ions, and all of the compounds demonstrate 2D layer
      structures. Rb2Te4O9.2H2O in centrosymmetric space group Pccn features a new
      [Te4O9]infinity2- anion sheet consisting of rare [Te8O22]12- groups.
      RbNaTe8O14(OH)6.8H2O in CS space group P1 exhibits a [Te4O9]infinity2- anion
      layer by linkage of the TeO3 and TeO4 units. NaPb4Te4O12F located in CS space
      group P4/ n displays an unusual [PbTeO3]infinity neutral layer made up of PbO3
      and TeO3 trigonal pyramids. RbK3Te8O18.5H2O lying in noncentrosymmetric (NCS)
      space group Cc shows a [Te4O9]infinity2- anion layer composed of the TeO3 and
      TeO4 units; its second-harmonic-generation response is about 0.2 times that of
      KH2PO4; structure analysis and local dipole moment calculation verify that the
      weak polarization mostly from the [Te4O9]infinity2- layer results from the
      inverse arrangement of TeO n units, and further theoretical calculation confirms
      that TeO n groups dominate the band gap of RbK3Te8O18.5H2O and optical
      properties. Meanwhile, systematic analyses of a series of metal tellurites reveal
      that the alkali-metal cations exert a considerable impact on polarization of the
      crystal structures, which puts forward a feasible idea about the design of new
      NCS materials.

PMID- 29641190
TI  - Ir(III)-Catalyzed Carbocarbation of Alkynes through Undirected Double C-H Bond
      Activation of Anisoles.
AB  - A novel, electron-deficient cyclopentadienyl iridium(III) catalyst enables
      sequential cleavage of arene C(sp2)-H and methoxy C(sp3)-H bonds of anisoles,
      generating reactive metalacycles that insert difluoroalkynes to afford chromenes
      under mild reaction conditions. This transformation is an arylalkylation of an
      alkyne-a carbocarbation-via a nonchelate-assisted cleavage of two C-H bonds.

PMID- 29641193
TI  - Localized Vibrations of Bi Bilayer Leading to Ultralow Lattice Thermal
      Conductivity and High Thermoelectric Performance in Weak Topological Insulator n
      Type BiSe.
AB  - Realization of high thermoelectric performance in n-type semiconductors is of
      imperative need on account of the dearth of efficient n-type thermoelectric
      materials compared to the p-type counterpart. Moreover, development of efficient
      thermoelectric materials based on Te-free compounds is desirable because of the
      scarcity of Te in the Earth's crust. Herein, we report the intrinsic ultralow
      thermal conductivity and high thermoelectric performance near room temperature in
      n-type BiSe, a Te-free solid, which recently has emerged as a weak topological
      insulator. BiSe possesses a layered structure consisting of a bismuth bilayer
      (Bi2) sandwiched between two Bi2Se3 quintuple layers [Se-Bi-Se-Bi-Se], resembling
      natural heterostructure. High thermoelectric performance of BiSe is realized
      through the ultralow lattice thermal conductivity (kappalat of ~0.6 W/mK at 300
      K), which is significantly lower than that of Bi2Se3 (kappalat of ~1.8 W/mK at
      300 K), although both of them belong to the same layered homologous family (Bi2)
      m(Bi2Se3) n. Phonon dispersion calculated from first-principles and the
      experimental low-temperature specific heat data indicate that soft localized
      vibrations of bismuth bilayer in BiSe are responsible for its ultralow kappalat.
      These low energy optical phonon branches couple strongly with the heat carrying
      acoustic phonons, and consequently suppress the phonon mean free path leading to
      low kappalat. Further optimization of thermoelectric properties of BiSe through
      Sb substitution and spark plasma sintering (SPS) results in high ZT ~ 0.8 at 425
      K along the pressing direction, which is indeed remarkable among Te-free n-type
      thermoelectric materials near room temperature.

PMID- 29641194
TI  - One-Dimensional Chains of Paddlewheel-Type Dichromium(II,II) Tetraacetate
      Complexes: Study of Electronic Structure Influenced by sigma- and pi-Donation of
      Axial Linkers.
AB  - Paddlewheel-type carboxylate-bridged dichromium(II,II) complexes possess
      intriguing properties such as high redox activity and thermally assisted
      paramagnetism. However, the relationship of their structures with electronic
      states and physical properties has not been extensively studied. In this work, we
      investigated a series of one-dimensional chain complexes based on the paddlewheel
      type dichromium(II,II) tetraacetate complex ([Cr2II,II(OAc)4] = [Cr2II,II]) with
      pyridine/pyrazine-type organic linkers (MU2-Lax) having different sigma- and pi
      donating abilities to clarify the electronic structure of [Cr2II,II] assemblies.
      The chain compounds are stable in air, probably owing to their robust polymerized
      forms. X-ray crystallographic studies and magnetic measurements revealed that the
      basicity (p Kb) of Lax, which quantitatively correlates with the sigma-donor
      strength of Lax, modulates the Cr-Cr and Cr-Lax distances and the energy
      separation ( ES-T) between the diamagnetic (singlet) and thermally populated
      paramagnetic (triplet) states. The Cr-Cr and Cr-Lax distances are strongly
      influenced by sigma- and pi-donation from Lax, while the frontier delta orbital
      makes only a small contribution to the structural features. Density functional
      theory calculations were conducted to clarify this issue. The calculations
      produced the following unanticipated results against the long-known model: (i)
      the sigma bonding orbital is the HOMO and dominates bonding in the [Cr2II,II]
      unit, (ii) the total Cr-Cr bond order is less than 1.0, and (iii) the delta
      orbital electron density is almost completely localized on the chromium sites.
      The computational results accurately predict the magnetic behavior and provide
      evidence for a new configuration of frontier orbitals in [Cr2II,II(RCO2)4(Lax)2].

PMID- 29641195
TI  - Oxidative Ring Contraction of Cyclobutenes: General Approach to
      Cyclopropylketones including Mechanistic Insights.
AB  - An original oxidative ring contraction of easily accessible cyclobutene
      derivatives for the selective formation of cyclopropylketones (CPKs) under
      atmospheric conditions is reported. Comprehensive mechanistic studies are
      proposed to support this novel, yet unusual, rearrangement. Insights into the
      mechanism ultimately led to simplification and generalization of the ring
      contraction of cyclobutenes using mCPBA as an oxidant. This unique and functional
      group tolerant transformation proceeds under mild conditions at room temperature,
      providing access to a new library of polyfunctionalized motifs. With CPKs being
      attractive and privileged pharmacophores, the elaboration of such a simple and
      straightforward strategy represents a highly valuable tool for drug discovery and
      medicinal chemistry. Additionally, the described method was employed to generate
      a pool of bioactive substances and key precursors in a minimum number of steps.

PMID- 29641196
TI  - Influence of Agricultural Management on Phytochemicals of Colored Corn Genotypes
      ( Zea mays L.). Part 2: Sowing Time.
AB  - Among the agronomic practices carried out in corn cultivation, the early sowing
      time is increasingly used by farmers of temperate regions to improve yield and
      reduce mycotoxin contamination of corn grains. The present study determined the
      influence of sowing time on the phytochemical content of grains of 10 colored
      genotypes of corn. There was a significant improvement of both grain yield
      (+26%), thousand kernel weight (+3%), and test weight (+2%) in plots sown early.
      The early sowing also significantly influenced the chemical composition of corn
      grains, with an increase in the concentration of cell-wall-bound phenolic acids
      (+5%) and beta-cryptoxanthin (+23%) and a decrease in the concentration of lutein
      (-18%) and total anthocyanins (-21%). Environmental conditions that occurred
      during grain development significantly influenced the phytochemical content of
      corn grain, and early spring sowing could impart advantages in terms of both
      productivity and content of some antioxidants of whole-meal corn flour.

PMID- 29641197
TI  - Electronic Spectra of Cs2NaYb(NO2)6: Is There Quantum Cutting?
AB  - The crystal structure and electronic spectra of the T h symmetry
      hexanitritoytterbate(III) anion have been studied in Cs2NaY0.96Yb0.04(NO2)6,
      which crystallizes in the cubic space group Fm3. The emission from Yb3+ can be
      excited via the NO2- antenna. The latter electronic transition is situated at
      more than twice the energy of the former, but at room temperature, one photon
      absorbed at 470 nm in the triplet state produces no more than one photon emitted.
      Some degree of quantum cutting is observed at 298 K under 420 nm excitation into
      the singlet state and at 25 K using excitation into either state. The quantum
      efficiency is ~10% at 25 K. The energy level scheme of Yb3+ has been deduced from
      excitation and emission spectra and calculated by crystal field theory. New
      improved energy level calculations are also reported for the Cs2NaLn(NO2)6 (Ln =
      Pr, Eu, Tb) series using the f- Spectra package. The neat crystal Cs2NaYb(NO2)6
      has also been studied, but results were unsatisfactory due to sample
      decomposition, and this chemical instability makes it unsuitable for
      applications.

PMID- 29641198
TI  - Jahn-Teller Effect of the Benzene Radical Cation: A Direct ab Initio Molecular
      Dynamics Study.
AB  - The benzene radical cation (Bz+) is a typical model molecule of the Jahn-Teller
      (J-T) active species. Bz+ has two structural forms due to the J-T effect. These
      are the compressed and elongated forms, expressed as Bz+(comp) and Bz+(elong),
      respectively. In Bz+(comp), the hexagonal structure of the benzene ring is
      compressed up and down, and in Bz+(elong), it is pulled up and down. From
      electron spin resonance experiments, it was found that Bz+ takes a compressed
      form in low-temperature Freon matrices (CF3Cl and CF2ClCFCl2), whereas the
      elongated form was found in argon matrices. However, the selectivity of these
      structural forms is still unclear. In this study, the ionization dynamics of
      isolated benzene (Bz) and benzene-M complexes (where M denotes counter-molecules,
      M = NH3, H2O, CF3Cl, CH4, CH3OH, Ar, SH2, ammonia dimer, or water dimer) have
      been investigated by means of the direct ab initio molecular dynamics (AIMD)
      method in order to shed light on the Bz+ formation mechanism. The static ab
      initio calculations showed that Bz+(comp) is slightly more energetically stable
      than Bz+(elong), although the energy difference was only 0.1 kcal/mol at the
      CCSD/6-311++G(d,p) level. The direct AIMD calculations indicated that Bz+(comp)
      was formed from the Bz-M complexes when M was NH3, CF3Cl, or an ammonia dimer,
      whereas the ionization of Bz-M when M was H2O, CH4, CH3OH, SH2, or a water dimer
      formed Bz+(elong). In the case of complexes with an argon dimer, Bz(Ar)2, both
      forms were obtained from a slight orientation change of Ar on Bz. A selective
      rule is discussed on the basis of the calculated results.

PMID- 29641199
TI  - Influence of Agricultural Management on Phytochemicals of Colored Corn Genotypes
      ( Zea mays L.). Part 1: Nitrogen Fertilization.
AB  - In this study, the influence of nitrogen (N) fertilization (170 versus 300 kg of
      N/ha) on the content of bioactive compounds of whole-meal flour of 10 different
      colored corn genotypes was investigated. Considerable differences in antioxidant
      capacity and phytochemical concentrations were observed among genotypes. Higher N
      fertilization rates significantly ( p < 0.05) increased the content of both total
      cell-wall-bound phenolics and xanthophylls (lutein and zeaxanthin). Nevertheless,
      the main phenolic acids (ferulic, p-coumaric, and sinapic acids) as well as the
      antioxidant capacity and content of beta-cryptoxanthin, beta-carotene, and total
      anthocyanins did not show significant differences as far as the N fertilization
      rate is concerned. For corn cultivation, the application of high N fertilization
      rates, generally carried out to obtain higher grain yields, could positively
      influence the content of some bioactives particularly in years characterized by
      high rainfall levels responsible for N leaching from the soil.

PMID- 29641200
TI  - Holistic Approach to Partial Covalent Interactions in Protein Structure
      Prediction and Design with Rosetta.
AB  - Partial covalent interactions (PCIs) in proteins, which include hydrogen bonds,
      salt bridges, cation-pi, and pi-pi interactions, contribute to thermodynamic
      stability and facilitate interactions with other biomolecules. Several score
      functions have been developed within the Rosetta protein modeling framework that
      identify and evaluate these PCIs through analyzing the geometry between
      participating atoms. However, we hypothesize that PCIs can be unified through a
      simplified electron orbital representation. To test this hypothesis, we have
      introduced orbital based chemical descriptors for PCIs into Rosetta, called the
      PCI score function. Optimal geometries for the PCIs are derived from a
      statistical analysis of high-quality protein structures obtained from the Protein
      Data Bank (PDB), and the relative orientation of electron deficient hydrogen
      atoms and electron-rich lone pair or pi orbitals are evaluated. We demonstrate
      that nativelike geometries of hydrogen bonds, salt bridges, cation-pi, and pi-pi
      interactions are recapitulated during minimization of protein conformation. The
      packing density of tested protein structures increased from the standard score
      function from 0.62 to 0.64, closer to the native value of 0.70. Overall, rotamer
      recovery improved when using the PCI score function (75%) as compared to the
      standard Rosetta score function (74%). The PCI score function represents an
      improvement over the standard Rosetta score function for protein model scoring;
      in addition, it provides a platform for future directions in the analysis of
      small molecule to protein interactions, which depend on partial covalent
      interactions.

PMID- 29641201
TI  - Nuclear Quantum Effects and Thermodynamic Properties for Small (H2O)1-21X-
      Clusters (X- = F-, Cl-, Br-, I-).
AB  - We carried out accurate diffusion Monte Carlo (DMC) studies for small (H2O) NX-
      clusters ( N = 1-5; X- = F-, Cl-, Br-, I-) and their D2O isotopologues. We found
      remarkably good agreement (i.e., ~0.1 kcal/mol or better) with no exceptions
      between the DMC solvation energies and the corresponding harmonic approximation
      (HA) estimates, due, apparently, to massive error cancellations. This is
      surprising, in particular, because HA does not account for a substantial (i.e., ~
      3%) increase of the mean O-O distances, caused by the anharmonicity in
      conjunction with the nuclear quantum effects, although the other distances in the
      system are affected to a much lesser extent. This agreement for the solvation
      energies motivated us to extend the current study to larger ( N = 6-21) clusters
      to explore their thermodynamic properties using the harmonic superposition method
      (HSM). The HSM results for the solvation free energies in turn reveal that at
      finite temperatures the nuclear quantum effects (including the isotope effects)
      in these systems are miniscule.

PMID- 29641202
TI  - Bonding Properties and Oxidation States of Plutonium in Pu2O n ( n = 1-8)
      Molecules Studied by Using Screened Hybrid Density Functional Theory.
AB  - The structural and electronic properties of Pu2O n ( n = 1-8) molecules have been
      systematically studied within the screened hybrid density functional theory. On
      the basis of the calculations, plutonium and oxygen generally prefers forming Pu
      O and Pu-O-Pu bonds over to Pu-Pu or O-O bonds. In the ground-state geometries,
      we find that the highest oxidation state for plutonium atoms is Pu(VI). Through
      fragmentation studies, we find that the Pu2O and Pu2O2 molecules are
      energetically stable among all studied compounds. When fixing the Fermi level to
      be energy zero, the Pu-5 f states always distribute at the two sides of the Fermi
      level. With increasing the number of oxygen atoms and the oxidation state of
      plutonium, the Pu-6d states shift down from above to below the Fermi level.

PMID- 29641203
TI  - Prenylcoumarins in One or Two Steps by a Microwave-Promoted Tandem Claisen
      Rearrangement/Wittig Olefination/Cyclization Sequence.
AB  - The one-pot synthesis of 8-prenylcoumarins from 1,1-dimethylallylated
      salicylaldehydes and the stabilized ylide
      [(ethoxycarbonyl)methylene]triphenylphosphorane under microwave conditions was
      found to have a limited scope. The sequence suffers from a difficult and
      sometimes low-yielding synthesis of the precursors and from a competing
      deprenylation upon microwave irradiation. This side reaction occurs in particular
      with electron rich arenes with two or more alkoxy groups at adjacent positions, a
      prominent substitution pattern in naturally occurring 8-prenylcoumarins. Both
      limitations of this one-step sequence were overcome by a two-step synthesis
      consisting of a microwave-promoted tandem allyl ether Claisen
      rearrangement/Wittig olefination and a subsequent olefin cross metathesis with 2
      methyl-2-butene. The cross metathesis step proceeds with a high selectivity and
      yields exclusively the desired prenyl, rather than the alternative crotyl
      substituent. Several naturally occurring 8-prenylcoumarins that were previously
      inaccessible have been synthesized in good overall yields along this route.

PMID- 29641205
TI  - Modified Julia-Kocienski Reagents for a Stereoselective Introduction of
      Trisubstituted Double Bonds: A Formal Total Synthesis of Limazepine E and
      Barmumycin.
AB  - A formal total synthesis of pyrrolo[1,4]benzodiazepine anticancer antibiotic
      family member limazepine E is described. The synthesis features a stereoselective
      introduction of a trisubstituted double bond using novel sterically demanding
      Julia-Kocienski reagents, allowing the number of linear steps to be significantly
      reduced. The potential of the newly developed reagents has also been demonstrated
      by the formal total synthesis of barmumycin.

PMID- 29641204
TI  - Natural Product Micheliolide (MCL) Irreversibly Activates Pyruvate Kinase M2 and
      Suppresses Leukemia.
AB  - Metabolic reprogramming of cancer cells is essential for tumorigenesis in which
      pyruvate kinase M2 (PKM2), the low activity isoform of pyruvate kinase, plays a
      critical role. Herein, we describe the identification of a nature-product-derived
      micheliolide (MCL) that selectively activates PKM2 through the covalent binding
      at residue cysteine424 (C424), which is not contained in PKM1. This interaction
      promotes more tetramer formation, inhibits the lysine433 (K433) acetylation, and
      influences the translocation of PKM2 into the nucleus. In addition, the pro-drug
      dimethylaminomicheliolide (DMAMCL) with similar properties as MCL significantly
      suppresses the growth of leukemia cells and tumorigenesis in a zebrafish
      xenograft model. Cell-based assay with knock down PKM2 expression verifies that
      the effects of MCL are dependent on PKM2 expression. DMAMCL is currently in
      clinical trials in Australia. Our discovery may provide a valuable
      pharmacological mechanism for clinical treatment and benefit the development of
      new anticancer agents.

PMID- 29641207
TI  - Formation of Tertiary Alcohols from the Rhodium-Catalyzed Reactions of
      Donor/Acceptor Carbenes with Esters.
AB  - Rhodium(II)-catalyzed reactions between isopropyl acetate and trichloroethyl
      aryldiazoacetates result in the formation of oxirane intermediates that ring open
      under the reaction conditions to form tertiary alcohols. When the reaction is
      catalyzed by the dirhodium tetrakis(triarylcyclopropanecarboxylate) complex, Rh2(
      S-2-Cl,4-BrTPCP)4, the tertiary alcohols are formed with good asymmetric
      induction (80-88% ee).

PMID- 29641206
TI  - Estrogen Receptor (ER) Subtype Selectivity Identifies 8-Prenylapigenin as an
      ERbeta Agonist from Glycyrrhiza inflata and Highlights the Importance of Chemical
      and Biological Authentication.
AB  - Postmenopausal women are increasingly using botanicals for menopausal symptom
      relief due to the increased breast cancer risk associated with traditional
      estrogen therapy. The deleterious effects of estrogens are associated with
      estrogen receptor (ER)alpha-dependent proliferation, while ERbeta activation
      could enhance safety by opposing ERalpha effects. Three medicinal licorice
      species, Glycyrrhiza glabra ( G. glabra), G. uralensis, and G. inflata, were
      studied for their differential estrogenic efficacy. The data showed higher
      estrogenic potency for G. inflata in an alkaline phosphatase induction assay in
      Ishikawa cells (ERalpha) and an estrogen responsive element (ERE)-luciferase
      assay in MDA-MB-231/beta41 breast cancer cells (ERbeta). Bioassay-guided
      fractionation of G. inflata led to the isolation of 8-prenylapigenin (3).
      Surprisingly, a commercial batch of 3 was devoid of estrogenic activity. Quality
      control by MS and qNMR revealed an incorrect compound, 4'- O
      methylbroussochalcone B (10), illustrating the importance of both structural and
      purity verification prior to any biological investigations. Authentic and pure 3
      displayed 14-fold preferential ERbeta agonist activity. Quantitative analyses
      revealed that 3 was 33 times more concentrated in G. inflata compared to the
      other medicinal licorice extracts. These data suggest that standardization of G.
      inflata to 3 might enhance the safety and efficacy of G. inflata supplements used
      for postmenopausal women's health.

PMID- 29641208
TI  - In Situ and Real-Time Studies, via Synchrotron X-ray Scattering, of the
      Orientational Order of Cellulose Nanocrystals during Solution Shearing.
AB  - In this manuscript, we report on the ordering of the cellulose nanocrystals
      (CNCs) as they experience shear forces during the casting process. To achieve
      these measurements, in situ and in real time, we used synchrotron-based grazing
      incidence wide-angle X-ray scattering (GIWAX). We believe that the GIWAX
      technique, although not commonly used to probe these types of phenomena, can open
      new avenues to gain deeper insights into film formation processes and surface
      driven phenomena. In particular, we investigated the influence of solution
      concentration, shear-cast velocity, and drying temperature on the ordering of
      cellulose nanocrystals (CNCs) using GIWAXS. The films were prepared from aqueous
      suspensions of cellulose nanocrystals at two concentration values (7 and 9 wt %).
      As the films were cast, the X-ray beam was focused on a fixed position and GIWAXS
      patterns were recorded at regular time intervals. Structural characterization of
      the dry films was carried out via polarized optical microscopy and scanning
      electron microscopy. In addition, a rheological study of the CNC suspensions was
      performed. Our results show that the morphology of the CNC films was
      significantly influenced by shear velocity, concentration of the precursor
      suspension, and evaporation temperature. In contrast, we observed that the
      orientation parameter of the films was not significantly affected. The scattering
      intensity of the peak (200) was analyzed as a function of time, following a
      sigmoidal profile, hence indicating short- and long-range interactions within the
      anisotropic domains as they reached their final orientation state. A model
      capable of describing the resulting film morphologies is also proposed. The
      results and analysis presented in this manuscript provide new insights into the
      controlled alignment of cellulose nanocrystals under shear. This controlled
      alignment has significant implications in the development of advanced coatings
      and films currently used in a myriad of applications, such as catalysis, optics,
      electronics, and biomedicine.

PMID- 29641209
TI  - A Cost-Effective High-Throughput Plasma and Serum Proteomics Workflow Enables
      Mapping of the Molecular Impact of Total Pancreatectomy with Islet
      Autotransplantation.
AB  - Blood is an ideal body fluid for the discovery or monitoring of diagnostic and
      prognostic protein biomarkers. However, discovering robust biomarkers requires
      the analysis of large numbers of samples to appropriately represent
      interindividual variability. To address this analytical challenge, we established
      a high-throughput and cost-effective proteomics workflow for accurate and
      comprehensive proteomics at an analytical depth applicable for clinical studies.
      For validation, we processed 1 MUL each from 62 plasma samples in 96-well plates
      and analyzed the product by quantitative data-independent acquisition liquid
      chromatography/mass spectrometry; the data were queried using feature
      quantification with Spectronaut. To show the applicability of our workflow to
      serum, we analyzed a unique set of samples from 48 chronic pancreatitis patients,
      pre and post total pancreatectomy with islet autotransplantation (TPIAT) surgery.
      We identified 16 serum proteins with statistically significant abundance
      alterations, which represent a molecular signature distinct from that of chronic
      pancreatitis. In summary, we established a cost-efficient high-throughput
      workflow for comprehensive proteomics using PVDF-membrane-based digestion that is
      robust, automatable, and applicable to small plasma and serum volumes, e.g.,
      finger stick. Application of this plasma/serum proteomics workflow resulted in
      the first mapping of the molecular implications of TPIAT on the serum proteome.

PMID- 29641210
TI  - Dynamics of Influenza-induced Lung-Resident Memory T Cells, Anatomically and
      Functionally Distinct Lung Mesenchymal Populations, and Dampening of Acute Lung
      Injury by Neutrophil Transfer of Micro-RNA-223 to Lung Epithelial Cells.

PMID- 29641211
TI  - Reply to Mummadi et al.: Overfitting and Use of Mismatched Cohorts in Deep
      Learning Models: Preventable Design Limitations.

PMID- 29641212
TI  - Efficacy of Hippotherapy Versus Pharmacotherapy in Attention
      Deficit/Hyperactivity Disorder: A Randomized Clinical Trial.
AB  - OBJECTIVES: Pharmacotherapy among children with attention-deficit/hyperactivity
      disorder (ADHD) is effective, but many patients suffer from secondary psychiatric
      problems even after improvement of ADHD core symptoms. Hippotherapy have been
      used as adjunct treatment options for physical and psychosocial rehabilitation as
      well as to ameliorate core symptoms. The aim of this study was to investigate the
      effects of Hippotherapy versus pharmacotherapy for children with ADHD. DESIGN:
      Thirty-four participants with ADHD were randomly assigned at a 1:1 ratio to
      either 24 sessions of a twice-weekly hippotherapy or pharmacotherapy. To assess
      therapeutic effects, the ADHD Rating Scale (ARS) was used pretreatment and
      posttreatment as the primary outcome measure. Secondary outcomes included the
      Child Behavior Checklist (CBCL), Self-Esteem Scale (SES), Pediatric Quality of
      Life Inventory (PedsQL) child and parent report version, Developmental
      Coordination Disorder Questionnaire (DCDQ), Clinical Global Impressions-Severity
      (CGI-S), and quantitative electroencephalography. RESULTS: Both groups showed
      marked improvements in ADHD symptoms, CGI-S. No significant differences between
      groups were detected regarding treatment outcome except thought problem subscales
      of CBCL. Twelve weeks of hippotherapy improved attention,
      impulsivity/hyperactivity, and quality of life. CONCLUSION: This trial is
      promising, but further studies are required to evaluate the long-term clinical
      effectiveness of hippotherapy. The study is registered with ClinicalTrials.gov,
      number NCT 02482649.

PMID- 29641217
TI  - Overfitting and Use of Mismatched Cohorts in Deep Learning Models: Preventable
      Design Limitations.

PMID- 29641213
TI  - Systemic IL-6 regulation of eccentric contraction-induced muscle protein
      synthesis.
AB  - Systemic cytokines and contractile activity are established regulators of muscle
      protein turnover. Paradoxically, the IL-6 cytokine family, which shares the
      ubiquitously expressed membrane gp130 receptor, has been implicated in skeletal
      muscle's response to both contractions and cancer-induced wasting. Although we
      have reported that tumor-derived cachectic factors could suppress stretch-induced
      protein synthesis in cultured myotubes, the ability of systemic cytokines to
      disrupt in vivo eccentric contraction-induced protein synthesis has not been
      established. Therefore, we examined whether systemic IL-6 regulates basal and
      eccentric contraction-induced protein synthesis through muscle gp130 signaling.
      Systemic IL-6 overexpression was performed for 2 wk, and we then examined basal
      and eccentric contraction-induced protein synthesis and mammalian target of
      rapamycin complex 1 (mTORC1) signaling in tibialis anterior muscle of male wild
      type, muscle-specific gp130 receptor knockout, and tumor-bearing ApcMin/+ mice.
      Systemic IL-6 overexpression suppressed basal protein synthesis and mTORC1
      signaling independently of IL-6 level, which was rescued by muscle gp130 loss.
      Interestingly, only high systemic IL-6 levels suppressed eccentric contraction
      induced protein synthesis. Systemic IL-6 overexpression in precachectic tumor
      bearing ApcMin/+ mice accelerated cachexia development, which coincided with
      suppressed basal and eccentric contraction-induced muscle protein synthesis. The
      suppression of eccentric contraction-induced protein synthesis by IL-6 occurred
      independently of mTORC1 activation. Collectively, these findings demonstrate that
      basal protein synthesis suppression was more sensitive to circulating IL-6
      compared with the induction of protein synthesis by eccentric contraction.
      However, systemic IL-6 can interact with the cancer environment to suppress
      eccentric contraction-induced protein synthesis independently of mTORC1
      activation.

PMID- 29641218
TI  - Forced into aging: Analytical prediction of the flavor-stability of lager beer. A
      review.
AB  - Despite years of research, sensory deterioration during beer aging remains a
      challenge to brewing chemists. Therefore, sensorial and analytical tools to
      investigate aging flavors are required. This review aims to summarize the
      available analytical methods and to highlight the problems associated with
      addressing the flavor-stability of beer. Carbonyls are the major contributors to
      the aroma of aged pale lager beer, which is especially susceptible to
      deterioration. They are formed via known pathways during storage, but, as recent
      research indicates, are mainly released from the bound-state during aging.
      However, most published studies are based on model systems, and thus the
      formation and breakdown parameters of these adducts are poorly understood. This
      concept has not been previously considered in previous forced-aging analysis.
      Only weak parallels can be drawn between forced and natural aging. This is likely
      due to the different activation energies of the chemical processes responsible
      for aging, but may also be due to heat-promoted release of bound aldehydes. Thus,
      precursors and their binding parameters must be investigated to make appropriate
      technological adjustments to forced-aging experiments. In combination with
      sophisticated data analysis, the investigation of volatile indicators and non
      volatile precursors can lead to more reliable predictions of flavor stability.

PMID- 29641219
TI  - Mechanical Ventilation in Acute Respiratory Distress Syndrome. Insights into
      Opening the Lung and Driving Pressure.

PMID- 29641220
TI  - Enantioseparation by Capillary Electrophoresis Using Ionic Liquids as Chiral
      Selectors.
AB  - Capillary electrophoresis (CE) is one of the most widely employed analytical
      techniques to achieve enantiomeric separations. In spite of the fact that there
      are many chiral selectors commercially available to perform enantioseparations by
      CE, one of the most relevant topics in this field is the search for new selectors
      capable of providing high enantiomeric resolutions. Chiral ionic liquids (CILs)
      have interesting characteristics conferring them a high potential in chiral
      separations although only some of them are commercially available. The aim of
      this article is to review all the works published on the use of CILs as chiral
      selectors in the development of enantioselective methodologies by CE, covering
      the period from 2006 (when the first research work on this topic was published)
      to 2017. The use of CILs as sole chiral selectors, as chiral selectors in dual
      systems or as chiral ligands will be considered. This review also provides
      detailed analytical information on the experimental conditions used to carry out
      enantioseparations in different fields as well as on the separation mechanism
      involved.

PMID- 29641221
TI  - Airway Pressure Release Ventilation in Pediatric Acute Respiratory Distress
      Syndrome. A Randomized Controlled Trial.
AB  - RATIONALE: Although case series describe benefits of airway pressure release
      ventilation (APRV), this mode of ventilation has not been evaluated against the
      conventional low-tidal volume ventilation (LoTV) in children with acute
      respiratory distress syndrome (ARDS). OBJECTIVES: To compare the effect of APRV
      and conventional LoTV on ventilator-free days in children with ARDS. METHODS:
      This open-label, parallel-design randomized controlled trial was conducted in a
      15-bed ICU. Children aged 1 month to 12 years satisfying the modified Berlin
      definition were included. We excluded children with air leaks, increased
      intracranial pressure, poor spontaneous breathing efforts, chronic lung disease,
      and beyond 24 hours of ARDS diagnosis or 72 hours of ventilation. Children were
      randomized using unstratified, variable-sized block technique. A priori interim
      analysis was planned at 50% enrollment. All enrolled children were followed up
      until 180 days after enrollment or death, whichever was earlier. MEASUREMENTS AND
      MAIN RESULTS: The trial was terminated after 50% enrollment (52 children) when
      analysis revealed higher mortality in the intervention arm. Ventilator-free days
      were statistically similar in both arms (P = 0.23). The 28-day all-cause
      mortality was 53.8% in APRV as compared with 26.9% among control subjects (risk
      ratio, 2.0; 95% confidence interval, 0.97-4.1; Fisher exact P = 0.089). The
      multivariate-adjusted risk ratio of death for APRV compared with LoTV was 2.02
      (95% confidence interval, 0.99-4.12; P = 0.05). Higher mean airway pressures,
      greater spontaneous breathing, and early improvement in oxygenation were seen in
      the intervention arm. CONCLUSIONS: APRV, as a primary ventilation strategy in
      children with ARDS, was associated with a trend toward higher mortality compared
      with the conventional LoTV. Limitations should be considered while interpreting
      these results. Clinical trial registered with www.clinicaltrials.gov
      (NCT02167698) and Clinical Trials Registry of India (CTRI/2014/06/004677).

PMID- 29641222
TI  - Kava for Generalized Anxiety Disorder: A Review of Current Evidence.
AB  - BACKGROUND: Generalized anxiety disorder (GAD) is a chronic and debilitating
      condition characterized by persistent and overpowering anxiety. Treatment of GAD
      with antidepressants and benzodiazepines is only moderately effective and not
      free from side effects. Kava (Piper methysticum) has been explored as a potential
      phytotherapeutic option for GAD. OBJECTIVES: To perform a systematic review and
      meta-analysis of the available evidence on Kava as a treatment for GAD. METHODS:
      Systematic search of English-language publications from major databases for
      clinical trials reporting the effects of Kava for the treatment of GAD. RESULTS:
      Twelve articles were included in this review. Evidence supporting Kava as an
      effective treatment for GAD was found in two placebo-controlled trials and a
      reference-controlled trial. One negative trial demonstrated that Kava was not
      more effective than placebo. Meta-analyses of the results of three placebo
      controlled trials (n = 130) favored Kava for GAD treatment with effect sizes
      between 0.59 and 0.99 (standard mean difference) without reaching statistical
      significance. Kava is an appealing treatment option to GAD patients who are more
      attune to natural remedies or lifestyle approaches to reduce stress. Positive
      patient experiences and improvement of vagal cardiac control due to Kava
      treatment were also reported in the literature. Kava is safe and well tolerated
      for short-term (4-8 weeks) therapeutic use at a dosage of 120-280 mg per day of
      Kavalactones, regardless of dosage schedule. CONCLUSIONS: Current evidence,
      although promising, is insufficient to confirm the effect of Kava for GAD
      treatment beyond placebo. New evidence is expected from a large, multisite
      ongoing trial.

PMID- 29641223
TI  - Safety and feasibility audit of a home-based drug-transitioning approach for
      patients with pulmonary arterial hypertension: an observational study.
AB  - BACKGROUND: Newer endothelin receptor antagonists (ERAs) used to treat patients
      with pulmonary arterial hypertension (PAH) are associated with fewer drug-drug
      interactions than bosentan and require less monitoring. This, combined with a
      pharmacokinetic basis for improved efficacy, means there may be a clinical
      rationale for changing therapies. However, this can be challenging and few data
      on its safety in patients with PAH are available. AIMS: At the Royal Free
      Hospital in London, UK, home-based medication transitioning has been standard
      practice since 2009 to avoid unnecessary hospital visits for patients, unless
      there is a clinical imperative. In this audit of standard practice we evaluated
      the consequences of adopting such a strategy when transitioning PAH patients
      between ERA therapies. METHODS AND RESULTS: Using a Clinical Nurse Specialist
      led, home-based transitioning strategy, 92 patients with PAH were transitioned
      from bosentan to macitentan or ambrisentan. Observational data were analysed
      retrospectively. The majority of patients were female with PAH associated with
      connective tissue disease and their ERA was changed in the hope of improving
      efficacy. The process was well tolerated with no adverse events associated with
      the process. Seventeen patients died during the study (macitentan, n = 5;
      ambrisentan, n = 12). None of the deaths was considered related to ERA treatment.
      The majority of patients remained clinically stable, based on WHO functional
      class and exercise capacity. CONCLUSION: An established home-based transitioning
      strategy can be adopted safely for patients with PAH changing ERA therapies. Most
      patients remained stable and the therapy change was well tolerated.

PMID- 29641224
TI  - Breast cancer: influence of tumour volume estimation method at MRI on prediction
      of pathological response to neoadjuvant chemotherapy.
AB  - OBJECTIVE: Does method of tumour volume measurement on MRI influence prediction
      of treatment outcome in patients with primary breast cancer undergoing
      neoadjuvant chemotherapy (NAC)?. METHOD: The study comprised of 136 women with
      biopsy-proven breast cancer scheduled for MRI monitoring during NAC treatment.
      Dynamic contrast-enhanced images were acquired at baseline (pre-NAC) and interim
      (post three NAC cycles) time points. Functional tumour volumes (FTVs),
      automatically derived using vendor software and enhancing tumour volumes (ETVs),
      user-derived using a semi-automated thresholding technique, were calculated at
      each time point and percentage changes calculated. Response, assessed using
      residual cancer burden (RCB) score on surgically resected specimens, was compared
      statistically with volumetric changes and receiver operating characteristic
      analysis performed. RESULTS: Mean volumetric differences for each RCB response
      category were (FTV/ETV): pathological complete response (pCR) 95.5/96.8%, RCB-I
      69.8/66.7%, RCB-II 64.0/65.5%, RCB-III 25.4/24.0%. Differences were significant
      between pCR and RCB-II/RCB-III categories (p < 0.040; unpaired t-test) using FTV
      measures and between pCR and RCB-I/RCB-II/RCB-III categories (p < 0.006; unpaired
      t-test) when ETV was used. Receiver operating characteristic analysis for pCR
      identification post-NAC yielded area under the curve for FTV/ETV of 0.834/0.920
      respectively. Sensitivity and specificity for FTV was 80.0 and 76.8% for FTV and
      81.0 and 91.8% for ETV. CONCLUSION: ETV changes can identify patients likely to
      achieve a complete response to NAC. Potentially, this could impact patient
      management regarding the possible avoidance of post-NAC surgery. Advances in
      Knowledge: Interim changes in ETV are more useful than FTV in predicting final
      pathological response to NAC. ETV differentiates patients who will achieve a
      complete response from those who will have residual disease.

PMID- 29641225
TI  - Developmental Origins of Chronic Lung Diseases. Mechanical Stretch, Micro-RNAs,
      and Hydrogels.

PMID- 29641226
TI  - The impact of contrast-enhanced spectral mammogram (CESM) and three-dimensional
      breast ultrasound (3DUS) on the characterization of the disease extend in cancer
      patients.
AB  - OBJECTIVE: The main importance of imaging breast cancer is to guide conservative
      surgeries. In this study, we evaluated the role of contrast-enhanced spectral
      mammogram (CESM) in correlation with three-dimensional (3D) breast ultrasound in
      characterizing the extension of the intramammary cancer in view of the: (i) the
      size of the main tumor, (ii) the multiplicity of the breast cancer, and (iii) the
      peri-tumoral stromal involvement (i.e. free or intraductal extension of the
      cancer). METHODS: The study is a prospective analysis that included 300 breast
      masses proved to be malignant. The masses were evaluated for their size,
      multiplicity and surrounding stromal involvement. Contrast-based mammography
      performed with low (22-33 kVp) and high (44-49 kVp) energy exposures that were
      taken after i.v. injection of contrast agent and followed by bilateral 3D breast
      ultrasound. Operative data were the gold standard reference. RESULTS: There was
      no significant difference between the sizes of the included cancers as measured
      by CESM and 3D ultrasound and that measured at the pathological analysis. CESM
      showed higher accuracy (32.7%, n = 98) than 3D ultrasound (24.7%, n = 74) in the
      size agreement within 5% range. CESM was the most accurate modality (94%, n =
      282) in detecting tumor multiplicity, followed by traditional sonomammogram (88%,
      n = 264), then 3D breast ultrasound (84%, n = 252). Intraductal extension of the
      breast cancer was best evaluated by the 3D ultrasound with an accuracy value of
      98% (n = 294) compared to only 60% (n = 180) by CESM. CONCLUSION: CESM is a
      recommended investigation in breast cancer to increase the accuracy of size
      measurement and the detection of multiple tumors. The addition of 3D ultrasound
      can enhance the detection of intraductal extension. Advances in knowledge: Choice
      of conservative breast surgery vs mastectomy is still a debate. We used an
      advanced, contrast-based, application of the mammogram: CESM and a non-invasive
      3D breast ultrasound in the assessment of the local extension of the breast
      cancer regarding size, perifocal stromal infiltration and multiplicity to guide
      the selection of proper management in proved cases of breast cancer.

PMID- 29641228
TI  - REDO: RNA Editing Detection in Plant Organelles Based on Variant Calling Results.
AB  - RNA editing is a post-transcriptional or cotranscriptional process that changes
      the sequence of the precursor transcript by substitutions, insertions, or
      deletions. Almost all of the land plants undergo RNA editing in organelles
      (plastids and mitochondria). Although several software tools have been developed
      to identify RNA editing events, there has been a great challenge to distinguish
      true RNA editing events from genome variation, sequencing errors, and other
      factors. Here we introduce REDO, a comprehensive application tool for identifying
      RNA editing events in plant organelles based on variant call format files from
      RNA-sequencing data. REDO is a suite of Perl scripts that illustrate a bunch of
      attributes of RNA editing events in figures and tables. REDO can also detect RNA
      editing events in multiple samples simultaneously and identify the significant
      differential proportion of RNA editing loci. Comparing with similar tools, such
      as REDItools, REDO runs faster with higher accuracy, and more specificity at the
      cost of slightly lower sensitivity. Moreover, REDO annotates each RNA editing
      site in RNAs, whereas REDItools reports only possible RNA editing sites in
      genome, which need additional steps to obtain RNA editing profiles for RNAs.
      Overall, REDO can identify potential RNA editing sites easily and provide several
      functions such as detailed annotations, statistics, figures, and significantly
      differential proportion of RNA editing sites among different samples.

PMID- 29641227
TI  - Primary postpartum hemorrhage: outcome of uterine artery embolization.
AB  - OBJECTIVE: To assess the efficacy of uterine artery embolization (UAE) for the
      management of primary postpartum hemorrhage (PPH) and to determine the factors
      associated with clinical outcomes especially in relation to the ovarian artery.
      METHODS: A retrospective analysis of 33 patients who underwent UAE for primary
      PPH was performed. Clinical data were used regarding maternal characteristics,
      cause of bleeding, mode of delivery, bleeding onset after delivery, risk factors
      for PPH, presence of coagulopathy, details regarding the UAE procedure, and types
      of ovarian artery flow. We defined two types of ovarian artery flow by initial
      aortography before UAE (Type A: ovarian artery flow arose directly from the aorta
      to the uterine artery; Type B: ovarian artery flow that did not obviously arise
      from the aorta). Clinical success was defined as cessation of bleeding after UAE
      without the need for hysterectomy. Univariate analysis was performed to determine
      factors related to clinical outcomes. RESULTS: The major indication of UAE was
      uterine atony (82%; 27/33). Extravasation of contrast medium was observed in 15
      (45%) patients. The clinical success rate was 85% (28/33). In five patients,
      embolization failed, and these patients were managed by hysterectomy. Univariate
      analysis showed that retained placental tissue (p < 0.001), type of ovarian
      artery (p < 0.001) and the existence of extravasation of contrast medium (p =
      0.049) were related to the clinical success rate. CONCLUSION: The clinical
      success rate was 85% (28/33), and some PPH patients were thought to need ovarian
      artery embolization in addition to UAE. Advances in knowledge: Initial
      aortography before UAE may be useful to predict the failure of UAE and the need
      of ovarian artery embolization. Obvious ovarian arterial blood flow to the uterus
      by aortography could be a warning sign.

PMID- 29641229
TI  - Coumarins improved type 2 diabetes induced by high-fat diet and streptozotocin in
      mice via antioxidation.
AB  - Coumarins extensively exist in plants and are utilized against diabetes in some
      folk medicines. Recent studies have demonstrated that oxidative stress plays a
      crucial role in the etiology and pathogenesis of diabetes mellitus. We
      investigated the antioxidant ability of 3 coumarins (osthole, esculin, and
      fraxetin) in type 2 diabetes. After being fed a high-fat diet, ICR mice were
      exposed to low doses of streptozotocin and then treated with experimental
      coumarins for 5 weeks. We found osthole, esculin, and metformin significantly
      lowered fasting blood glucose, HOMA-IR, and 3 blood lipids (total cholesterol,
      total triglyceride, free fatty acids), and increased insulin levels, while
      fraxetin only enhanced insulin levels and lessened free fatty acids. Both osthole
      and esculin had antioxidative effects in pancreas through elevating the
      activities of glutathione peroxidase, catalase, and superoxide dismutase;
      fraxetin, however, merely heightened catalase activity. By contrast, 3 coumarins
      significantly increased those antioxidase activities in liver. Hematoxylin and
      eosin staining revealed 3 coumarins, especially osthole, attenuated cellular
      derangement, blurry fringes of hepatic sinusoid and extensive vacuolization due
      to hepatocellular lipid accumulation, and lessened inflammatory infiltration in
      pancreas. The glomerular and islet structure of diabetic mice were improved, with
      reduced mesangial matrix and glomerular basement membrane thickening. Therefore,
      our study supports that coumarins could be promising candidates against type 2
      diabetes through antioxidative mechanisms.

PMID- 29641230
TI  - PyPathway: Python Package for Biological Network Analysis and Visualization.
AB  - Life science studies represent one of the biggest generators of large data sets,
      mainly because of rapid sequencing technological advances. Biological networks
      including interactive networks and human curated pathways are essential to
      understand these high-throughput data sets. Biological network analysis offers a
      method to explore systematically not only the molecular complexity of a
      particular disease but also the molecular relationships among apparently distinct
      phenotypes. Currently, several packages for Python community have been developed,
      such as BioPython and Goatools. However, tools to perform comprehensive network
      analysis and visualization are still needed. Here, we have developed PyPathway,
      an extensible free and open source Python package for functional enrichment
      analysis, network modeling, and network visualization. The network process module
      supports various interaction network and pathway databases such as Reactome,
      WikiPathway, STRING, and BioGRID. The network analysis module implements
      overrepresentation analysis, gene set enrichment analysis, network-based
      enrichment, and de novo network modeling. Finally, the visualization and data
      publishing modules enable users to share their analysis by using an easy web
      application. For package availability, see the first Reference.

PMID- 29641232
TI  - Soleus muscle stability in wild hibernating black bears.
AB  - Based on studies of fast skeletal muscles, hibernating black and brown bears
      resist skeletal muscle atrophy during months of reduced physical activity and not
      feeding. The present study examined atrophy sparing in the slow soleus muscle,
      known to be highly prone to disuse atrophy in humans and other mammals. We
      demonstrated histochemically that the black bear soleus is rich in slow fibers,
      averaging 84.0 +/- 6.6%. The percentages of slow fibers in fall (87.3 +/- 4.9%)
      and during hibernation (87.1 +/- 5.6%) did not differ ( P = 0.3152) from summer.
      The average fiber cross-sectional area to body mass ratio (48.6 +/- 11.7 um2/kg)
      in winter hibernating bears was not significantly different from that of summer
      (54.1 +/- 11.8 um2/kg, P = 0.4186) and fall (47.0 +/- 9.7 um2/kg, P = 0.9410)
      animals. The percentage of single hybrid fibers containing both slow and fast
      myosin heavy chains, detected biochemically, increased from 2.6 +/- 3.8% in
      summer to 24.4 +/- 24.4% ( P = 0.0244) during hibernation. The shortening
      velocities of individual hybrid fibers remained unchanged from that of pure slow
      and fast fibers, indicating low content of the minority myosins. Slow and fast
      fibers in winter bears exhibited elevated specific tension (kN/m2; 22%, P =
      0.0161 and 11%, P = 0.0404, respectively) and maintained normalized power. The
      relative stability of fiber type percentage and size, fiber size-to-body mass
      ratio, myosin heavy chain isoform content, shortening velocity, power output, and
      elevated specific tension during hibernation validates the ability of the black
      bear to preserve the biochemical and performance characteristics of the soleus
      muscle during prolonged hibernation.

PMID- 29641231
TI  - A role for the CXCR4-CXCL12 axis in the little skate, Leucoraja erinacea.
AB  - The interaction between C-X-C chemokine receptor type 4 (CXCR4) and its cognate
      ligand C-X-C motif chemokine ligand 12 (CXCL12) plays a critical role in
      regulating hematopoietic stem cell activation and subsequent cellular
      mobilization. Extensive studies of these genes have been conducted in mammals,
      but much less is known about the expression and function of CXCR4 and CXCL12 in
      non-mammalian vertebrates. In the present study, we identify simultaneous
      expression of CXCR4 and CXCL12 orthologs in the epigonal organ (the primary
      hematopoietic tissue) of the little skate, Leucoraja erinacea. Genetic and
      phylogenetic analyses were functionally supported by significant mobilization of
      leukocytes following administration of Plerixafor, a CXCR4 antagonist and
      clinically important drug. Our results provide evidence that, as in humans,
      Plerixafor disrupts CXCR4/CXCL12 binding in the little skate, facilitating
      release of leukocytes into the bloodstream. Our study illustrates the value of
      the little skate as a model organism, particularly in studies of hematopoiesis
      and potentially for preclinical research on hematological and vascular disorders.

PMID- 29641233
TI  - Efficacy and safety of antenatal steroids.
AB  - Antenatal steroids (ANS) are among the most important and widely utilized
      interventions to improve outcomes for preterm infants. A significant body of
      evidence demonstrates improved outcomes in preterm infants (24-34 wk) delivered
      between 1 and 7 days after the administration of a single course of ANS.
      Moreover, ANS have the advantage of being widely available, low cost, and easily
      administered via maternal intramuscular injection. The use of ANS to mature the
      fetal lung is, however, not without contention. Their use in pregnancy is not FDA
      approved, and treatment doses and regimens remain largely unoptimized. Their mode
      of use varies considerably between countries, and there are lingering concerns
      regarding the safety of exposing the fetus to high doses of exogenous steroids. A
      significant proportion of women deliver outside the 1- to 7-day therapeutic
      window after ANS treatment, and this delay may be associated with an increased
      risk of adverse outcomes for both mother and baby. Today, animal-based studies
      are one means by which key questions of dosing and safety relating to ANS may be
      resolved, allowing for further refinement(s) of this important therapy.
      Complementary approaches using nonhuman primates, sheep, and rodents have
      provided invaluable advances to our understanding of how exogenous steroid
      exposure impacts fetal development. Focusing on these three major model groups,
      this review highlights the role of three key animal models (sheep, nonhuman
      primates, rodents) in the development of antenatal steroid therapy, and provides
      an up-to-date synthesis of current efforts to refine this therapy in an era of
      personalised medicine.

PMID- 29641234
TI  - Adipose cell size: importance in health and disease.
AB  - Adipose tissue is necessary to harbor energy. To handle excess energy, adipose
      tissue expands by increasing adipocyte size (hypertrophy) and number
      (hyperplasia). Here, we have summarized the different experimental techniques
      used to study adipocyte cell size and describe adipocyte size in relation to
      insulin resistance, type 2 diabetes, and diet interventions. Hypertrophic
      adipocytes have an impaired cellular function, and inherent mechanisms restrict
      their expansion to protect against cell breakage and subsequent inflammation.
      Reduction of large fat cells by diet restriction, physical activity, or bariatric
      surgery therefore is necessary to improve cellular function and health. Small fat
      cells may also be dysfunctional and unable to expand. The distribution and
      function of the entire cell size range of fat cells, from small to very large fat
      cells, are an important but understudied aspect of adipose tissue biology. To
      prevent dysmetabolism, therapeutic strategies to expand small fat cells, recruit
      new fat cells, and reduce large fat cells are needed.

PMID- 29641235
TI  - Time course of red blood cell intracellular pH recovery following short
      circuiting in relation to venous transit times in rainbow trout, Oncorhynchus
      mykiss.
AB  - Accumulating evidence is highlighting the importance of a system of enhanced
      hemoglobin-oxygen (Hb-O2) unloading for cardiovascular O2 transport in teleosts.
      Adrenergically stimulated sodium-proton exchangers (beta-NHE) create H+ gradients
      across the red blood cell (RBC) membrane that are short-circuited in the presence
      of plasma-accessible carbonic anhydrase (paCA) at the tissues; the result is a
      large arterial-venous pH shift that greatly enhances O2 unloading from pH
      sensitive Hb. However, RBC intracellular pH (pHi) must recover during venous
      transit (31-90 s) to enable O2 loading at the gills. The halftimes ( t1/2) and
      magnitudes of RBC beta-adrenergic stimulation, short-circuiting with paCA and
      recovery of RBC pHi, were assessed in vitro, on rainbow trout whole blood, and
      using changes in closed-system partial pressure of O2 as a sensitive indicator
      for changes in RBC pHi. In addition, the recovery rate of RBC pHi was assessed in
      a continuous-flow apparatus that more closely mimics RBC transit through the
      circulation. Results indicate that: 1) the t1/2 of beta-NHE short-circuiting is
      likely within the residence time of blood in the capillaries, 2) the t1/2 of RBC
      pHi recovery is 17 s and within the time of RBC venous transit, and 3) after
      short-circuiting, RBCs reestablish the initial H+ gradient across the membrane
      and can potentially undergo repeated cycles of short-circuiting and recovery.
      Thus, teleosts have evolved a system that greatly enhances O2 unloading from pH
      sensitive Hb at the tissues, while protecting O2 loading at the gills; the
      resulting increase in O2 transport per unit of blood flow may enable the
      tremendous athletic ability of salmonids.

PMID- 29641236
TI  - Nationwide Epidemiologic Study of Atypical Antipsychotic Use Among Pediatric
      Population with Mental Illness in Korea.
AB  - OBJECTIVE: This population-based epidemiologic study aimed to analyze the
      prevalence and trends of atypical antipsychotic (AAP) use and identify factors
      associated with AAP prescribing among children and adolescents in Korea. METHODS:
      Using the Health Insurance Review and Assessment Service-Pediatric Patients
      Sample data between 2010 and 2014, we assessed the prevalence of and secular
      trends in AAP use; utilization of individual AAP drug based on the type of
      healthcare services, healthcare institutions, and health security programs; and
      factors associated with AAP use. RESULTS: The average annual prevalence of AAP
      use was 417 per 100,000 children and adolescents, which increased by 40% from
      2010 to 2014. The major AAP drug of choice has shifted from risperidone (72.70%
      and 49.29% in 2010 and 2014, respectively) to aripiprazole (11.31% and 34.64% in
      2010 and 2014, respectively). Quetiapine was mainly prescribed for inpatients.
      Therefore, hospitals have 2-3 times higher proportion of quetiapine use than
      clinics. A prominent difference exists in the prescribing rates and AAP drug of
      choice based on income level. Patients enrolled in the Medical Aid (MA) program
      had a higher AAP prescription rate than those enrolled in the National Health
      Insurance (NHI) program (adjusted odds ratio: 7.78). Moreover, MA recipients were
      more frequently prescribed with cheaper alternatives, such as risperidone,
      compared with NHI recipients. CONCLUSION: AAP has been increasingly used among
      the pediatric population in Korea. Future studies are needed to identify the
      causes of this increase and establish evidence on appropriate AAP use. In
      addition, relevant policies should be developed to ensure that low-income
      mentally ill children could take advantage of the best available therapy.

PMID- 29641237
TI  - Optimization of Methylphenidate Extended-Release Chewable Tablet Dose in Children
      with ADHD: Open-Label Dose Optimization in a Laboratory Classroom Study.
AB  - OBJECTIVE: To examine methylphenidate extended-release chewable tablets (MPH
      ERCT) dose patterns, attention-deficit/hyperactivity disorder (ADHD) symptom
      scores, and safety during the 6-week, open-label (OL) dose-optimization period of
      a phase 3, laboratory classroom study. METHODS: Boys and girls (6-12 years)
      diagnosed with ADHD were enrolled. MPH ERCT was initiated at 20 mg/day;
      participants were titrated in 10-20 mg/day increments weekly based on efficacy
      and tolerability (maximum dose, 60 mg/day). Dose-optimization period efficacy
      assessments included the ADHD Rating Scale (ADHD-RS-IV), analyzed by week in a
      post hoc analysis using a mixed-effects model for repeated measures with final
      optimized dose (20, 30/40, or 50/60 mg), visit, final optimized dose and visit
      interaction, and baseline score as terms. Adverse events (AEs) and concomitant
      medications were collected throughout the study. RESULTS: Mean MPH ERCT daily
      dose increased weekly from 29.4 mg/day after the first dose adjustment at week 1
      (n = 90) to 42.8 mg/day after the final adjustment at week 5 (n = 86). Final
      optimized MPH ERCT dose ranged from 20 to 60 mg/day. Mean final optimized MPH
      ERCT dose ranged from 40.0 mg/day in 6-8 year-old participants to 44.8 mg/day for
      11-12 year-old participants. There was a progressive decrease in mean (standard
      deviation) ADHD-RS-IV total score from 40.1 (8.72) at baseline to 12.4 (7.88) at
      OL week 5, with similar improvement patterns for hyperactivity/impulsivity and
      inattentiveness subscale scores. Participants optimized to MPH ERCT 50/60 mg/day
      had a significantly higher mean (standard error) ADHD-RS-IV score at baseline
      compared with participants optimized to MPH ERCT 20 mg/day (42.4 [1.34] vs. 35.1
      [2.55]; p = 0.013). Treatment-emergent AEs were reported by 65/90 (72.2%)
      participants in the dose-optimization period. CONCLUSIONS: Dose-optimization
      period results describing relationships between change in ADHD symptom scores and
      final optimized MPH ERCT dose will be valuable for clinicians optimizing MPH ERCT
      dose.

PMID- 29641239
TI  - Antipsychotics in Dutch Youth: Prevalence, Dosages, and Duration of Use from 2005
      to 2015.
AB  - OBJECTIVES: The use of antipsychotic drugs by youth is associated with serious
      side effects, especially when prescribed in higher dosages and for a longer
      period. Despite this, little is known about recent trends in the dosages and
      duration of use of antipsychotic drugs in children and adolescents. The aim of
      this study was to describe trends in prevalence, incidence, dosages, duration of
      use, and preceding psychotropic medication in Dutch youth who had been prescribed
      antipsychotic drugs from 2005 to 2015. METHODS: We analyzed 84,828 antipsychotic
      prescriptions of youths aged 0-19 years between 2005 and 2015, derived from a
      large Dutch community pharmacy-based prescription database (IADB.nl). RESULTS:
      Since a peak of 9.8 users per 1000 youths in 2009, prevalence rates stabilized.
      Dosages in milligram per kilogram declined for the most frequently prescribed
      antipsychotic drugs during the study period. The median duration of use was 6.0
      (95% CI 5.4-6.6) months. Boys used antipsychotic drugs significantly longer than
      girls, with a median of 6.9 (95% CI 6.1-7.7) versus 4.6 (95% CI 3.9-5.3) months
      (p < 0.01). Of the youths prescribed antipsychotics, 12.4% used them for at least
      48 months. The majority of youths had used other psychotropic agents in the year
      before the start of an antipsychotic drug (62.4% in 2005 and 64.7% in 2015).
      CONCLUSIONS: Despite a stabilization of usage rates and decline in dosages and
      duration of use, one in eight youths still used antipsychotic drugs for 4 years
      or longer. A substantial share of youths may, therefore, be at high risk for
      serious side effects.

PMID- 29641238
TI  - Comparing Nurse Practitioner and Physician Prescribing of Psychotropic
      Medications for Medicaid-Insured Youths.
AB  - OBJECTIVE: To describe psychotropic medication prescribing practices of nurse
      practitioners (NP) and physicians for Medicaid-insured youths in 2012-2014 in a
      mid-Atlantic state where NP independent prescribing is authorized. METHOD: From
      annual computerized administrative claims data in a mid-Atlantic state, we
      analyzed 1,034,798 dispensed psychotropic medications prescribed by NPs and
      physicians for 61,526 continuously enrolled Medicaid-insured youths aged 2-17
      years. Demographic and clinical characteristics of psychotropic medication users
      were compared for youths who received psychotropic medication dispensings by NP
      only, physician-only, or by both providers using descriptive statistics and
      generalized estimating equations. We then characterized psychotropic medication
      prescribing practices by providers within each specialty. RESULTS: From 2012 to
      2014, the number of psychotropic medication dispensings increased from 346,922 to
      349,080. There was a 50.9% increase in the proportion of psychotropic medications
      prescribed by psychiatric NPs (from 5.9% to 8.8%) and a 28.6% proportional
      increase by non-psychiatric NPs (from 4.9% to 6.3%). By contrast, the proportion
      of psychotropic medications prescribed by psychiatrists and by non-psychiatric
      physicians declined (56.9%-53.0% and 32.3%-31.8%, respectively). Youths diagnosed
      with depression or anxiety were more commonly treated by NP-only than by
      physician-only (AOR = 1.33, 95% CI = 1.24-1.43), whereas youths with two or more
      psychiatric comorbidities were significantly more commonly treated by both NP and
      physician providers (AOR = 1.44, 95% CI = 1.39-1.50). Psychiatric specialists
      prescribed the bulk of antidepressants (82.0%) and lithium (92.3%), with much
      lower prescribing by non-psychiatric specialists (18.0% and 7.7%, respectively).
      Antipsychotic orders originated from psychiatric specialists 7.4 times more than
      from their non-psychiatric specialty counterparts, whether physician or NP.
      CONCLUSIONS: NPs, relative to physicians, have taken an increasing role in
      prescribing psychotropic medications for Medicaid-insured youths. The quality of
      NP prescribing practices deserves further attention.

PMID- 29641240
TI  - Decreasing Trend in the Use and Long-Term Use of Benzodiazepines Among Young
      Adults.
AB  - OBJECTIVE: Patterns of benzodiazepine (BZD) use and long-term use among young
      adults are not well known. Our aim was to study trends in BZD use and long-term
      use among 18-25-year-old young adults by gender and active substance in a
      nationwide retrospective longitudinal register-based setting. METHODS: All Finns
      aged 18-25 years with reimbursed purchases of BZDs in 2006-2014 recorded to the
      Finnish Prescription Register were included. Annual prevalence rates of BZD use
      and long-term use among young adults were reported overall, according to gender,
      drug group (anxiolytic or hypnotic), and active substance. Long-term use of BZDs
      was defined as purchasing >=180 Defined Daily Doses (DDDs) in at least two drug
      purchases during a calendar year. RESULTS: Overall prevalence of BZD use among
      young adults decreased from 24.0 to 18.8 users per 1000 inhabitants in 2006-2014.
      Prevalence of long-term use decreased from 5.5 to 3.3 users per 1000 inhabitants.
      Overall BZD use was higher among females, whereas long-term use was more common
      among males. Use of anxiolytics was more common than use of hypnotics. Oxazepam,
      alprazolam, zopiclone, and zolpidem were the most used BZDs, whereas alprazolam
      and clonazepam were the substances with most long-term use. The use and long-term
      use of BZDs have decreased annually since 2008 among Finnish young adults.
      Further research is needed to investigate the reasons behind the decline.

PMID- 29641241
TI  - N-Acetyl Cysteine and Curcumin in Pediatric Acute-Onset Neuropsychiatric
      Syndrome.

PMID- 29641242
TI  - Matrix Analysis of Traditional Chinese Medicine Differential Diagnoses in Gulf
      War Illness.
AB  - OBJECTIVE: To qualitatively categorize Traditional Chinese Medicine (TCM)
      differential diagnoses in a sample of veterans with Gulf War Illness (GWI) pre-
      and postacupuncture treatment. SUBJECTS AND METHODS: The authors randomized 104
      veterans diagnosed with GWI to a 6-month acupuncture intervention that consisted
      of either weekly or biweekly individualized acupuncture treatments. TCM
      differential diagnoses were recorded at baseline and at 6 months. These TCM
      diagnoses were evaluated using Matrix Analysis to determine co-occurring patterns
      of excess, deficiency, and channel imbalances. These diagnoses were examined
      within and between participants to determine patterns of change and to assess
      stability of TCM diagnoses over time. RESULTS: Frequencies of diagnoses of
      excess, deficiency, and channel patterns were tabulated. Diagnoses of excess
      combined with deficiency decreased from 43% at baseline to 39% of the sample at 6
      months. Excess+deficiency+channel imbalances decreased from 26% to 17%, while
      deficiency+channel imbalances decreased from 11% to 4% over the study duration.
      The authors observed a trend over time of decreased numbers of individuals
      presenting with all three types of differential diagnosis combinations. This may
      suggest that fewer people were diagnosed with concurrent excess, deficiency, and
      channel imbalances and perhaps a lessening in the complexity of their
      presentation. CONCLUSION: This is the first published article that organizes and
      defines TCM differential diagnoses using Matrix Analysis; currently, there are no
      TCM frameworks for GWI. These findings are preliminary given the sample size and
      the amount of missing data at 6 months. Characterization of the TCM clinical
      presentation of veterans suffering from GWI may help us better understand the
      potential role that East Asian medicine may play in managing veterans with GWI
      and the design of effective acupuncture treatments based on TCM. The development
      of a TCM manual for treating GWI is merited.

PMID- 29641243
TI  - An Evolutionary Theory to Explain the Mechanism of Pain Control by Acupuncture
      Therapy.

PMID- 29641244
TI  - Adiponectin Increase in Mildly Obese Women After Massage Treatment.

PMID- 29641245
TI  - Evaluation of "Energy Resonance by Cutaneous Stimulation" Among Women Treated by
      In Vitro Fertilization.
AB  - OBJECTIVES: Pregnancy rate in in vitro fertilization (IVF) depends on many
      factors, such as the characteristics of the couple and the clinicobiological
      parameters. Interest in alternative and complementary medicine (ACM) for IVF is
      discussed because of the lack of scientific evidence. Energy resonance by
      cutaneous stimulation (ERCS), an acupuncture-like technique, consists of skin
      stimulation to transmit vibratory messages. The aim of this study was to evaluate
      the effect of ERCS on live birth rates (LBRs) in IVF. DESIGN: A prospective
      observation study was performed in the Unit of Assisted Reproductive Technologies
      of a University Teaching Hospital. Every woman who agreed to participate in this
      study and received a fresh embryo transfer (ET) after IVF or Intracytoplasmic
      Sperm Injection (ICSI) was included. Patients randomly underwent an ERCS session
      on the day of ET according to the schedule of the midwife performing this
      technique. The control group consisted of women undergoing ET under usual
      conditions. The main outcome measure was the LBR per transfer. RESULTS: Three
      hundred-eighteen women were included, 120 in the ERCS + ET group and 198 in the
      ET without ERCS group. None of the women dropped out. The clinical
      characteristics in both groups were comparable. There was a significant
      difference in the clinical pregnancy rates, 31.7% in the ERCS group versus 21.7%
      in the No ERCS group (p = 0.037). The LBR in the ERCS group was nearly
      significantly higher, 29.2% versus 20.7% in the No ERCS group (p = 0,059).
      CONCLUSIONS: Women undergoing ERCS on the day of ET had a significantly higher
      IVF pregnancy rate. However, this methodology made not possible to draw
      conclusions about the mechanisms that induced the increase of IVF LBRs: placebo
      effect, "cocooning," or ERCS self-effect? Further well-conducted studies are
      strongly needed to assess ERCS efficacy.

PMID- 29641246
TI  - Colonialism, Health Justice, and (Re)Examination of the Value of Traditional
      Practitioners and Licensed Integrative Health Professionals.

PMID- 29641247
TI  - Effect of Hydroalcoholic Extracts of Capsella Bursa-Pastoris on Heavy Menstrual
      Bleeding: A Randomized Clinical Trial.
AB  - OBJECTIVES: Heavy menstrual bleeding (HMB) is one of the leading causes of low
      quality of life and iron deficiency anemia in women. This study aimed to
      determine the effect of hydroalcoholic extracts of Capsella bursa-pastoris on
      HMB. DESIGN: This study is a triple-blinded, randomized clinical trial. SETTING:
      The study was conducted in gynecology clinics affiliated to Shahid Beheshti
      University of Medical Sciences, Tehran, Iran. SUBJECTS: Our patients affected to
      a complaint of HMB. After obtaining a complete medical history of the women and
      filling out the demographic forms, the participants were assigned randomly into
      the experimental (n = 42) and control groups (n = 42). INTERVENTION: The eligible
      participants were given a pictorial blood loss assessment chart (PBLAC) to
      confirm HMB during the menstrual cycle. The experimental group received two
      capsules of mefenamic acid (500 mg) every 8 h and two Capsella bursa-pastoris
      capsules every 12 h. The intervention started from the first day of menstruation
      to the end of this period up to 7 days for two consecutive cycles. In the control
      group, the patients received mefenamic acid and placebo instead of Capsella bursa
      pastoris capsules. OUTCOME MEASUREMENTS: The PBLAC score and number of bleeding
      days, incidence of any possible problems, as well as participant satisfaction
      were measured. The data were analyzed using t-test, Chi-square, repeated-measures
      ANOVA, and ANCOVA tests in PASW Statistics ver. 18. RESULTS: After the
      intervention, there was observed significant decrease in the amount of menstrual
      bleeding in both groups. However, the mean decrease in the amount of bleeding was
      significantly more in the Capsella bursa-pastoris group (p < 0/001). CONCLUSION:
      Compared with control group, hydroalcoholic extracts of Capsella bursa-pastoris
      capsule appeared to be effective in reducing menstrual bleeding in this study.
      Further research regarding the efficacy and safety of Capsella bursa-pastoris is
      required.

PMID- 29641248
TI  - Improved Search of Large Transcriptomic Sequencing Databases Using Split Sequence
      Bloom Trees.
AB  - Enormous databases of short-read RNA-seq experiments such as the NIH Sequencing
      Read Archive are now available. These databases could answer many questions about
      condition-specific expression or population variation, and this resource is only
      going to grow over time. However, these collections remain difficult to use due
      to the inability to search for a particular expressed sequence. Although some
      progress has been made on this problem, it is still not feasible to search
      collections of hundreds of terabytes of short-read sequencing experiments. We
      introduce an indexing scheme called split sequence bloom trees (SSBTs) to support
      sequence-based querying of terabyte scale collections of thousands of short-read
      sequencing experiments. SSBT is an improvement over the sequence bloom tree (SBT)
      data structure for the same task. We apply SSBTs to the problem of finding
      conditions under which query transcripts are expressed. Our experiments are
      conducted on a set of 2652 publicly available RNA-seq experiments for the breast,
      blood, and brain tissues. We demonstrate that this SSBT index can be queried for
      a 1000 nt sequence in <4 minutes using a single thread and can be stored in just
      39 GB, a fivefold improvement in search and storage costs compared with SBT.

PMID- 29641250
TI  - From the Editor-in-Chief's Desk.

PMID- 29641251
TI  - Medication Reconciliation: Making Bupropion Work After a "Bad Experience".

PMID- 29641249
TI  - BBK* (Branch and Bound Over K*): A Provable and Efficient Ensemble-Based Protein
      Design Algorithm to Optimize Stability and Binding Affinity Over Large Sequence
      Spaces.
AB  - Computational protein design (CPD) algorithms that compute binding affinity, Ka,
      search for sequences with an energetically favorable free energy of binding.
      Recent work shows that three principles improve the biological accuracy of CPD:
      ensemble-based design, continuous flexibility of backbone and side-chain
      conformations, and provable guarantees of accuracy with respect to the input.
      However, previous methods that use all three design principles are single
      sequence (SS) algorithms, which are very costly: linear in the number of
      sequences and thus exponential in the number of simultaneously mutable residues.
      To address this computational challenge, we introduce BBK*, a new CPD algorithm
      whose key innovation is the multisequence (MS) bound: BBK* efficiently computes a
      single provable upper bound to approximate Ka for a combinatorial number of
      sequences, and avoids SS computation for all provably suboptimal sequences. Thus,
      to our knowledge, BBK* is the first provable, ensemble-based CPD algorithm to run
      in time sublinear in the number of sequences. Computational experiments on 204
      protein design problems show that BBK* finds the tightest binding sequences while
      approximating Ka for up to 105-fold fewer sequences than the previous state-of
      the-art algorithms, which require exhaustive enumeration of sequences.
      Furthermore, for 51 protein-ligand design problems, BBK* provably approximates Ka
      up to 1982-fold faster than the previous state-of-the-art iMinDEE/[Formula: see
      text]/[Formula: see text] algorithm. Therefore, BBK* not only accelerates protein
      designs that are possible with previous provable algorithms, but also efficiently
      performs designs that are too large for previous methods.

PMID- 29641252
TI  - Special Issue Preface: 13th International Symposium on BioinformaticsResearch and
      Applications (ISBRA 2017).

PMID- 29641253
TI  - Constructing a Novel Hypoxia-Inducible Bidirectional shRNA Expression Vector for
      Simultaneous Gene Silencing in Colorectal Cancer Gene Therapy.
AB  - BACKGROUND: Nonspecific siRNA expression limits its application in cancer gene
      therapy. Therefore, a tightly regulated and reversibly inducible RNAi system is
      required to conditionally control the gene expression. This investigation aims at
      constructing a hypoxia/colorectal tumor dual-specific bidirectional short hairpin
      RNA (shRNA) expression vector. MATERIALS AND METHODS: First, carcinoma embryonic
      antigen (CEA) promoter designed in two directions. Then, pRNA-bipHRE-CEA vector
      was constructed by insertion of the vascular endothelial growth factor enhancer
      between two promoters for hypoxic cancer-specific gene expression. To confirm the
      therapeutic effect of the dual-specific vector, two shRNA oligonucleotides were
      inserted in the downstream of each promoter. QRT-polymerase chain reaction and
      western blot assays were performed to estimate the mRNA and protein expression
      levels. RESULTS: Both mRNA and protein levels were significantly reduced (50%
      60%) in the hypoxic colorectal cancer-treated cells when compared with the
      controls. CONCLUSION: The novel bidirectional hypoxia-inducible shRNA expression
      vector may be efficient in colorectal cancer-specific gene therapy.

PMID- 29641254
TI  - More Thoughts on Standards and Reproducibility.

PMID- 29641255
TI  - MiR-17 Regulates Prostate Cancer Cell Proliferation and Apoptosis Through
      Inhibiting JAK-STAT3 Signaling Pathway.
AB  - OBJECTIVE: STAT3 is an important protein in Janus kinase (JAK)-signal transducer
      and activator of transcription (STAT) signaling pathway that facilitates B-cell
      lymphoma 2 (Bcl-2) expression. MiR-17 was found to be significantly reduced in
      prostate cancer tissues and cells, suggesting that it might be a tumor suppressor
      in prostate cancer tumorigenesis. Bioinformatics analysis showed the
      complementary binding site between miR-17 and STAT3. This study aimed to
      investigate the role of miR-17 in regulating JAK-STAT signaling pathway, as well
      as prostate cancer cell proliferation and apoptosis. MATERIALS AND METHODS: Dual
      luciferase assay was used to verify the targeted relationship between miR-155 and
      STAT3. LNCaP cells were cultured in vitro and divided into four groups, including
      mimic NC, miR-17 mimic, si-NC, and si-STAT3 groups. STAT3, p-STAT3, and Bcl-2
      expressions were tested by western blot. Cell apoptosis was detected by flow
      cytometry. Cell proliferation was assessed by EdU staining. RESULTS: MiR-17 mimic
      transfection significantly reduced the relative luciferase activity in HEK293T
      cells. MiR-17 targeted regulated STAT3 expression. MiR-17 expression and cell
      apoptosis were obviously declined, while STAT3 level and cell proliferation
      markedly were elevated in LNCaP cells compared with RWPE-1 cells. MiR-17 mimic
      and/or si-STAT3 transfection significantly downregulated the expression of STAT3,
      p-STAT3, and Bcl-2, attenuated cell proliferation, and enhanced cell apoptosis in
      LNCaP cells. CONCLUSIONS: Upregulation of miR-17 inhibited LNCaP cell
      proliferation and induced cell apoptosis by downregulating the expression of
      STAT3, p-STAT3, and Bcl-2.

PMID- 29641257
TI  - Effects of Repeated Aurora-A siRNA Transfection on Cilia Generation and
      Proliferation of SK-MES-1 or A549 Cells.
AB  - BACKGROUND: Suppression of Aurora kinase A (Aurora-A, AURKA) by siRNA of Aurora-A
      (siAurora-A, siA) has been used in lung tumor treatment. However, the dose and
      frequency of gene transfection still need to be confirmed further. We imitated
      multiple administration of solid tumor and attempted to make out the effects of
      thrice transfection of siAurora-A on cilia generation and apoptosis of SK-MES-1
      cells (SK) or A549 cells. METHODS: The Aurora-A mRNA levels of cells cultured
      with serum for 6 d or without serum for 2, 4, or 6 d were examined with real-time
      quantitative PCR; Cells were transfected single or repeatedly with siAurora-A or
      siControl (siC), their Aurora-A mRNA levels were determined with PCR; Their cilia
      were examined with immunohistochemistry. Cell viability was measured with the MTT
      assay. Protein expression was analyzed with western blot. RESULTS: Cell viability
      showed a downward trend along with the prolongation of starvation time to the
      second, fourth, and even to the sixth day in both types of cells. But, the
      expression level of Aurora-A mRNA flipped to rise at the sixth day instead of
      decreasing at the fourth day. Protein expression trend of total Aurora-A in the
      two groups was consistent with Aurora-A mRNA expression trend. Compared with siC
      3 group (transfected three times with siControl), siAurora-A significantly
      reduced the Aurora-A mRNA expression in siA-3 group (transfected three times with
      siAurora-A). Similarly, the cell viability of siA-3 group was lower than that of
      siC-3 group. The cell viability of siC-3 group was higher than that of serum-free
      6d group, but, levels of Aurora-A mRNA expression of siC-3 group had no
      difference with serum-free-6d group. Finally, among groups transfected once or
      three times or starved for 6 d, there was no significant difference of ciliated
      cell proportions in both types of cells respectively. CONCLUSIONS: Repeated
      siAurora-A transfection decreased Aurora-A expression that resulted in effective
      suppression proliferation of SK-MES-1 or A549 cells, but did not affect cilia
      generation.

PMID- 29641258
TI  - Plantar Pressure Measurements and Geometric Analysis of Patients With and Without
      Morton's Neuroma.
AB  - BACKGROUND: The purpose of this research was to see if there were any differences
      in peak pressure, contact time, pressure-time integrals, and geometric variables
      such as forefoot width, foot length, coefficient of spreading, and arch index
      between subjects with Morton's neuroma (MN) and control subjects. METHODS:
      Dynamic peak plantar pressure, contact time, pressure-time integral, and
      geometric data were extracted using the EMED-X platform in 52 subjects with MN
      and 31 control subjects. Differences in peak pressure, contact time, pressure
      time integral, and geometric data between participants with and those without MN
      were determined using independent-samples t tests. There were no significant
      differences in age, weight, height, and body mass index between patients with MN
      and control subjects. RESULTS: There were no significant differences in the peak
      pressures of all masked areas and pressure-time integrals under metatarsal 2 to 4
      heads between patients with MN and control subjects. In addition, no significant
      differences were observed between patients with MN and control subjects in
      geometric measurements of forefoot length, width, coefficient of spreading, foot
      progression angle, and arch index. CONCLUSION: No relationship was found in this
      study between peak pressure, contact time, and pressure-time integral under the
      metatarsal heads, forefoot width, foot length, coefficient of spreading, and foot
      progression angle in a symptomatic MN group compared with a control group. The
      need to perform osteotomies to treat MN not associated with other lesser
      metatarsal phalangeal joint pathologies is questionable. LEVEL OF EVIDENCE: Level
      III, Case-Control Study.

PMID- 29641256
TI  - CLR 125 Auger Electrons for the Targeted Radiotherapy of Triple-Negative Breast
      Cancer.
AB  - PURPOSE: Auger electrons emitted by radioisotopes such as 125I have a high linear
      energy transfer and short mean-free path in tissue (<10 MUm), making them
      suitable for treating micrometastases while sparing normal tissues. The authors
      developed and subsequently investigated a cancer cell-selective small molecule
      phospholipid ether analog to deliver 125I to triple-negative breast cancer (TNBC)
      cells in vivo. METHODS: A Current Good Manufacturing Practice (cGMP) method to
      radiolabel 125I-CLR1404 (CLR 125) with >95% radiochemical purity was established.
      To estimate CLR 125 in vivo dosimetry and identify dose-limiting organs, the
      biodistribution of the analog compound 124I-CLR1404 (CLR 124) was investigated
      using micro-positron emission tomography (PET)/computed tomography (CT) in
      conjunction with a Monte Carlo dosimetry platform to estimate CLR 125 dosimetry.
      In vivo antitumor efficacy was tested by injecting nude mice bearing either MDA
      MB-231-luc orthotopic xenografts or lung metastases with 74 MBq (3.7 GBq/kg) of
      CLR 125 or an equivalent mass amount of nonradiolabeled CLR 125. Longitudinal
      tumor measurements using calipers and bioluminescence imaging were obtained for
      the xenografts and lung metastases, respectively. RESULTS: Dosimetry analysis
      estimated that CLR 125 would impart the largest absorbed dose to the tumor per
      injected activity (0.261 +/- 0.023 Gy/MBq) while the bone marrow, which is
      generally the dose-limiting organ for CLR1404, appears to have the lowest (0.063
      +/- 0.005 Gy/MBq). At administered activities of up to 74 MBq (3.7 GBq/kg), mice
      did not experience signs of toxicity. In addition, a single dose of CLR 125
      reduced the volume of orthotopic primary TNBC xenografts by ~60% compared to
      control vehicle (p < 0.001) and significantly extended survival. In addition, CLR
      125 was efficacious against preclinical metastatic TNBC models by inhibiting the
      progression of micrometastases (p < 0.01). CONCLUSIONS: Targeted radionuclide
      therapy with CLR 125 displayed significant antitumor efficacy in vivo, suggesting
      promise for treatment of TNBC micrometastases.

PMID- 29641259
TI  - Independent Coactors May Improve Performance and Lower Workload: Viewing
      Vigilance Under Social Facilitation.
AB  - OBJECTIVE: The purpose of the present study was to examine the effects of an
      independent coactor on vigilance task performance. It was hypothesized that the
      presence of an independent coactor would improve performance in terms of the
      proportion of false alarms while also increasing perceived workload and stress.
      BACKGROUND: Vigilance, or the ability to maintain attention for extended periods,
      is of great interest to human factors psychologists. Substantial work has focused
      on improving vigilance task performance, typically through motivational
      interventions. Of interest to vigilance researchers is the application of social
      facilitation as a means of enhancing vigilance. Social facilitation seeks to
      explain how social presence may improve performance. METHOD: A total of 100
      participants completed a 24-min vigil either alone or in the presence of an
      independent (confederate) coactor. Participants completed measures of perceived
      workload and stress. RESULTS: The results indicated that performance (i.e.,
      proportion of false alarms) was improved for those who completed the vigil in the
      presence of an independent coactor. Interestingly, perceived workload was
      actually lower for those who completed the vigil in the presence of an
      independent coactor, although perceived stress was not affected by the
      manipulation. CONCLUSION: Authors of future research should extend these findings
      to other forms of social facilitation and examine vigilance task performance in
      social contexts in order to determine the utility of social presence for
      improving vigilance. APPLICATION: The use of coactors may be an avenue for
      organizations to consider utilizing to improve performance because of its
      relative cost-effectiveness and easy implementation.

PMID- 29641261
TI  - Corrigendum.

PMID- 29641262
TI  - Results of External Fixation and Metatarsophalangeal Joint Fixation With K-Wire
      in Brachymetatarsia.
AB  - BACKGROUND: Brachymetatarsia is a rare foot deformity caused by the premature
      closure of the metatarsal physis. It may result in functional as well as cosmetic
      alterations, which may require operative management. METHODS: A prospective study
      examining outcomes of 48 cases of brachymetatarsia with gradual bone lengthening
      at a rate of 1 mm/d using an external fixator and metatarsophalangeal joint
      fixation was performed. The difference between the length before treatment and
      after external fixator removal was measured. The patients were assessed at 2, 4,
      6, and 8 weeks postoperatively; at the end of the period of distraction; and 1
      year after surgery. The total number of patients was 26, and surgery was
      performed in 48 metatarsals. The mean age was 17.0 +/- 4.1 (range, 11-24) years,
      and all were female. RESULTS: The fourth metatarsal was the most frequently
      affected, representing 98% of the cases; the third metatarsal represented the
      other 2%. The average length gained was 18.6 +/- 6.7 mm, and the average length
      gained as a proportion of the original metatarsal length was 38.2% +/- 3.1%
      (range, 13%-24%). The mean healing time was 71.0 (range, 64-104) days, and the
      mean healing index (healing time divided by centimeters of length gained [d/cm])
      was 38.4 (range, 38.2-50.1) d/cm. CONCLUSION: Gradual bone lengthening at a rate
      of 1 mm/d using an external fixator and intramedullary nailing was a safe and
      efficient method, representing a minimally invasive procedure with a low
      incidence of complications and satisfactory results for the patient. LEVEL OF
      EVIDENCE: Level IV, retrospective case series.

PMID- 29641260
TI  - A comparison of safety benefits of pedestrian countdown signals with and without
      pushbuttons in Michigan.
AB  - OBJECTIVE: This study evaluated the safety impacts of pedestrian countdown
      signals (PCSs) with and without pushbuttons based on pedestrian crashes and
      pedestrian injuries in Michigan. METHODOLOGY: This study used 10 years of
      intersection data-5 years before PCSs were installed and 5 years after they were
      installed-along with a comparison group, to evaluate the crash impacts of PCSs;
      at 107 intersections the PCS had a pushbutton and at 96 it did not. At these
      intersections, and at their comparison sites (where no PCS was installed), crash
      data (from 2004 to 2016) were examined, along with traffic and geometric
      characteristics, population, education, and poverty level data. RESULTS:
      Intersections where PCSs with pushbuttons have been installed showed a 29%
      reduction in total pedestrian crashes and a 30% reduction in fatal/injury
      pedestrian crashes. Further, when considering only pedestrians age 65 and below,
      these respective reductions are 33 and 35%. Intersections with PCSs but without
      pushbuttons did not show any significant change in any type of pedestrian crash.
      CONCLUSIONS: Although the Manual on Uniform Traffic Control Devices (Federal
      Highway Administration [FHWA] 2009 ) requires the use of PCSs at new traffic
      signal installations, this study suggests a safety benefit of installing PCSs
      with pushbutton at signals where a PCS without a pushbutton is present.

PMID- 29641263
TI  - Vitamin D supply in shift working nurses.
AB  - We studied determinants of Vitamin D in serum of 67 female health care workers
      (aged 25-60 years), including age, body mass index, physical activity, and shift
      work. Overall, vitamin D levels were low, ranging from 6 to 51 ng/mL (median: 20
      ng/mL). Lower serum levels were found in samples drawn in winter and spring and
      in obese subjects. Shift work had only small effects on vitamin D levels. The
      high prevalence of vitamin D undersupply is in line with observations from the
      German general population. Vitamin D supply particularly in winter and spring
      should be ensured to avoid health problems.

PMID- 29641264
TI  - Impulsivity interacts with momentary PTSD symptom worsening to predict alcohol
      use in male veterans.
AB  - BACKGROUND: Posttraumatic stress disorder (PTSD) is prevalent among veterans who
      served post-9/11, and co-occurs with problem alcohol and substance use. Studies
      using ecological momentary assessment have examined the temporal association
      between time-varying PTSD symptoms and alcohol use. Results suggest individual
      differences in these associations. OBJECTIVES: We tested hypotheses that alcohol
      use measured by momentary assessment would be explained by acute increases in
      PTSD symptoms, and the PTSD-alcohol association would be moderated by trait
      impulsivity. METHODS: A sample of 28 male post-9/11-era veterans who reported
      past-month PTSD symptoms and risky alcohol use were enrolled. On a quasi-random
      schedule, participants completed three electronic assessments daily for 28 days
      measuring past 2-h PTSD symptoms, alcohol, and substance use. At baseline, trait
      impulsivity was measured by the Barratt Impulsiveness Scale. Past-month PTSD
      symptoms and alcohol use were measured. Using three-level hierarchical models,
      number of drinks recorded by momentary assessment was modeled as a function of
      change in PTSD symptoms since last assessment, controlling for lag-1 alcohol and
      substance use and other covariates. A cross-level interaction tested moderation
      of the within-time PTSD-alcohol association by impulsivity. RESULTS: A total of
      1,522 assessments were completed. A positive within-time association between PTSD
      symptom change and number of drinks was demonstrated. The association was
      significantly moderated by impulsivity. CONCLUSION: Results provide preliminary
      support for a unique temporal relationship between acute PTSD symptom change and
      alcohol use among veterans with trait impulsiveness. If replicated in a clinical
      sample, results may have implications for a targeted momentary intervention.

PMID- 29641265
TI  - Meeting Report of the 33rd Annual Meeting of the Academy of Surgical Research:
      Summary of Presentations, Labs, and Workshops, Focusing on Experimental Surgery,
      Las Vegas, NV, October 4-6, 2017.
AB  - The 33rd Annual Meeting of the Academy of Surgical Research was held from October
      4 to 6, 2017 in Las Vegas, Nevada. The meeting welcomed >160 participants from 27
      different states and five countries representing the organization's diverse
      membership of technicians, veterinarians, medical doctors, and biomedical
      researchers. The Academy's annual meeting is focused on promoting the advancement
      of professional and academic standards, education, and research related to the
      art and science of experimental surgery. Presentations included four invited
      keynote speakers and 30 selected lectures and posters. A primary strength of the
      meeting was that lectures were complimented with practical sessions that included
      four wet lab and two dry lab half-day courses. Likewise, participants were
      brought together in workshops emphasizing research workflow from starting
      experimental design to readying results for publication. In this report, we
      present the highlights from this meeting and some selected abstracts that
      illustrate the diverse scientific expertise of the Academy and progress in
      surgical research.

PMID- 29641266
TI  - Lessons from Hawaii: A Blessing in Disguise.
AB  - On January 13, 2018, Hawaii experienced an erroneous alert that falsely warned of
      an imminent ballistic missile strike. Rather than focus on the inconvenience
      caused by the false alert, we used reporting of the event to identify the missing
      elements that would characterize a system that could save lives by alerting and
      informing the public in a nuclear detonation. These include warnings that contain
      essential information rather than directing recipients to secondary sources; a
      system that issues alerts directly from federal agencies that will have the
      earliest warning; a robust multimodal alerting system that can deliver messages
      before and after the detonation; and swift activation of federal agencies
      immediately upon warning.

PMID- 29641267
TI  - Oxidized Regenerated Cellulose Can Reduce Hidden Blood Loss after Total Hip
      Arthroplasty: A Retrospective Study.
AB  - BACKGROUND: There is a large amount of hidden blood loss (HBL) after total hip
      arthroplasty (THA), but the effective and safe methods to reduce HBL are still
      controversial. METHODS: Sixty-nine consecutive patients who underwent THA in our
      hospital from January 2015 to December 2015 were analyzed retrospectively. The
      patients were divided into two groups, Group A (THA without oxidized regenerated
      cellulose) and Group B (THA with oxidized regenerated cellulose). Demographics,
      perioperative laboratory values, intraoperative data, blood loss, transfusion
      rate, transfusion reactions, and surgical complications were collected and
      analyzed. RESULTS: A total of 37 (54%) patients used oxidized regenerated
      cellulose (ORC) in operation. The total blood loss (TBL), postoperative blood
      loss (PBL), hemoglobin (Hb) loss, and hidden blood loss (HBL) in group B were
      significantly lower than in group A. CONCLUSIONS: The use of ORC to fill the bone
      surface and soft tissue gap before incision closure can effectively reduce HBL
      and may be a potential treatment for blood prevention after THA.

PMID- 29641268
TI  - Medial Structure Injury During Suture Button Insertion Using the Center-Center
      Technique for Syndesmotic Stabilization.
AB  - BACKGROUND: The center-center technique for syndesmosis fixation has been
      described as an improved and reliable technique for proper reduction of the
      syndesmosis during ankle fracture repair. Concurrently, the use of flexible
      fixation with a suture button is becoming an established means of syndesmosis
      stabilization. The purpose of this cadaveric study was to assess for medial
      structure injury during the placement of a suture button using the center-center
      technique for ankle syndesmosis repair at 3 insertion intervals. METHODS:
      Simulated open syndesmosis repair was performed on 10 cadaveric specimens. Three
      intervals were measured at 10 mm, 20 mm, and 30 mm proximal to the level of the
      distal tibial articular surface along the fibula. Proper longitudinal alignment
      of the center-center technique was completed under fluoroscopic guidance and was
      marked on the medial aspect of the tibia. The 3 intervals were drilled in the
      appropriate technique trajectory. The suture button was subsequently passed
      through each drill-hole interval. A single observer used a digital caliper to
      measure the distance from each suture button aperture with respect to the
      tibialis anterior tendon, tibialis posterior tendon, and greater saphenous vein
      and nerve. RESULTS: A total of 30 interval measurements (10 cadavers with 3
      suture button segments each) were used for data analysis. Direct impingement on
      the greater saphenous vein was seen in 11 of 30 (36.6%) interval measurements.
      Six of the 11 (54.5%) observed saphenous structure impingement events occurred at
      the 10-mm drill hole. CONCLUSION: The results of the present study suggest that
      the use of the center-center technique for syndesmosis repair with suture button
      fixation risks preventable injury to the greater saphenous neurovasculature.
      CLINICAL RELEVANCE: To understand the medial ankle anatomy, as it pertains to
      insertion of flexible syndesmotic fixation in a cadaveric model, to aid in
      prevention of clinical iatrogenic injury.

PMID- 29641269
TI  - Association of secondhand smoke exposure with asthma symptoms, medication use,
      and healthcare utilization among asthmatic adolescents.
AB  - OBJECTIVE: To investigate the association between secondhand smoke exposure
      (SHSe) and asthma symptoms, medication use, and emergency department (ED)/urgent
      care (UC) utilization among adolescents. METHODS: We performed a secondary cross
      sectional analysis of Population Assessment of Tobacco and Health Study Wave 2
      (2014-2015) including asthmatic adolescents (N = 2198). Logistic regression
      models and Poisson regression models were built. RESULTS: Participants with SHSe
      >=1 hour in the past 7 days were at increased risk of reporting shortness of
      breath and harder to exercise aOR, 1.22; 95% CI, 1.04-1.43), wheezing (aOR, 1.26;
      95% CI, 1.01-1.56), wheezing disturbing sleep (aOR, 1.88; 95% CI, 1.35-2.63),
      wheezing during/after exercise (aOR, 1.41; 95% CI, 1.19-1.66), wheezing limiting
      speech (aOR, 2.11; 95% CI, 1.55-2.86), dry cough at night (aOR, 1.86; 95% CI,
      1.54-2.24), and asthma symptoms disturbing sleep (aOR, 2.25; 95% CI, 1.81-2.79).
      Participants with SHSe >=1 hour were more likely to take asthma medications (aOR,
      1.25; 95% CI, 1.03-1.52), including steroids (aOR, 1.86; 95% CI, 1.19-2.91),
      oxygen therapy (aOR, 2.88; 95% CI, 1.82-4.54), and controlling medications (aOR,
      1.50; 95% CI, 1.24-1.82). Symptoms and medications varied by living with a smoker
      and home SHSe. Participants with SHSe were at increased risk of having a higher
      number of asthma attacks that required steroid use. Participants who lived with a
      smoker and had home SHSe were at increased risk of having higher ED/UC visits for
      asthma. CONCLUSIONS: SHSe reduction efforts are needed for asthmatic adolescents,
      and EDs/UCs are promising venues.

PMID- 29641270
TI  - Preservation or Ligation of Splenic Vessels During Spleen-Preserving Distal
      Pancreatectomy: A Meta-Analysis.
AB  - : Purpose/aim: Spleen preservation distal pancreatectomy (SPDP) can be achieved
      by either splenic vessel preservation distal pancreatectomy (SVP-DP) or Warshaw
      technique (WT). Although studies comparing SVP-DP with WT have been reported,
      controversies exist. The aim of our study is to assess and compare the safety and
      feasibility of SVP-DP and WT. MATERIALS AND METHODS: Two authors searched the
      online database independently till April 30, 2017. Data extraction and quality
      assessment were performed independently by two authors. Short- and long-term
      outcomes of WT and SVP-DP were evaluated. Subgroup analysis was performed on
      laparoscopic surgery. Odds ratios (OR) with 95% confidence interval (CI) and mean
      difference (MD) with 95% CI were estimated. RESULTS: A total of 664 patients from
      11 retrospective cohort studies were included. Meta-analysis showed the WT group
      had a significantly higher incidence of splenic infarction (OR = 0.12; 95% CI:
      0.07-0.20; p < 0.00001) and gastric/epigastric varices (OR = 0.11; 95% CI: 0.05
      0.24; p < 0.00001). And more patients suffering from splenic infarction from WT
      group needed further splenectomy (OR = 0.13; 95% CI: 0.02-0.84; p = 0.03). While
      there was no difference between the two procedures in terms of pancreatic fistula
      (OR = 0.55; 95% CI: 0.25-1.19; p = 0.13), overall morbidity (OR = 0.87; 95% CI:
      0.59-1.30; p = 0.50) and hospital stay (MD = -0.45; 95% CI: -1.73-0.82; p =
      0.49). CONCLUSIONS: Due to relatively higher risk of postoperative splenic
      infarction, gastric/epigastric varices and Clavien-Dindo III-V complications, WT
      is not as safe as SVP-DP. However, well-conducted randomized clinical trials are
      still needed due to the limitations of current studies.

PMID- 29641271
TI  - Enhancing guideline-based asthma care processes through a multi-state, multi
      center quality improvement program.
AB  - OBJECTIVE: This study investigated the effectiveness of Enhancing Care for
      Patients with Asthma (ECPA)-a collaborative quality improvement program
      implemented in 65 community health centers that serve asthma patients in four
      states-on clinic-based asthma performance measures consistent with national
      guidelines. METHODS: This study utilized a pretest-posttest quasi-experimental
      design. Six clinic-based performance measures of each center were collected from
      a retrospective chart review at time points: before the ECPA implementation; at
      the end of the 12-month long ECPA program; and 6 months after program completion.
      The effectiveness of the ECPA was assessed using generalized linear mixed models
      with a Poisson distribution and log link by evaluating the change in each measure
      from baseline to program completion, from baseline to 6-month post-program
      completion and from program completion to 6-month post-program completion.
      RESULTS: The ECPA implementation was positively associated with improvement in
      all measures from baseline to program completion: documentation of asthma
      severity (rate ratio (RR) 1.314; 95% confidence interval (CI) 1.206, 1.432);
      Asthma Control Test (RR 3.625; 95% CI 3.185, 4.124); pulmonary function testing
      (RR 1.771; 95% CI 1.527, 2.054), asthma education (RR 2.246; 95% CI 2.018,
      2.501), asthma action plan (RR 2.335; 95% CI 2.070, 2.634) and controller
      medication (RR 1.961; 95% CI 1.504, 2.556). Improvement was sustained for all six
      measures at the 6-month post-program completion time point. CONCLUSION: This
      study demonstrated the favorable effect of the ECPA program on evidence-based
      asthma quality measures. This program could be considered a model worth
      replication on a broader scale.

PMID- 29641272
TI  - Impact of a Statewide Oral Oncolytic Initiative on Five Participating Practices.
AB  - PURPOSE: The shift from infusion to oral oncolytic therapy presents challenges to
      oncology practitioners. The purpose of this study was to describe how a statewide
      quality-improvement collaborative can enhance quality of care for patients
      receiving oral oncolytic therapy. METHODS: The Michigan Oncology Quality
      Consortium hosted a series of learning sessions focused on oral oncolytic quality
      improvement, providing multiple resources to oncology community practices. The
      first five participating practices reported which of the evidence-based Michigan
      Oncology Quality Consortium resources provided were implemented at their site.
      They also performed prepost self-assessments in October 2013 and April 2015 and
      another in December 2017 to assess sustainability. Concordance with the ASCO
      Quality Oncology Practice Initiative oral chemotherapy standards, including
      documentation (five measures), patient education (seven measures), and follow
      up/monitoring (four measures), was compared. RESULTS: All practices showed
      improvement between 2013 and 2015 in documentation (32% to 88%; P = .03), patient
      education (37% to 100%; P could not be calculated), and monitoring (40% to 80%; P
      > .2). Overall, a significant improvement in concordance was observed (36% to
      91%; P = .03). Use of resources from each practice varied, and practices that
      used more resources showed greater improvements. There was a slight decrease in
      overall concordance between 2015 and 2017, which was not found to be significant
      (91% to 84%; P = .53). CONCLUSION: Use of tools from a quality-improvement
      collaborative improved concordance with national standards of care. Large-scale
      deployment of this model program may provide a clinically efficient and effective
      mechanism to enhance widespread change.

PMID- 29641273
TI  - Monitoring InBaskets With Feedback to Providers Enhances the Timeliness of
      Patient Care.
AB  - PURPOSE: Electronic health records have changed providers' workflow. Epic's
      InBasket supplants traditional communication and is a central hub for clinical
      information. Failure to promptly complete records impairs communication and
      revenue collection. By tracking providers' InBasket activities and offering
      feedback, we hoped to improve InBasket management and interdisciplinary
      communication. METHODS: We created a report to track 273 providers' InBasket
      activities, including ambulatory transcriptions, chart cosignatures, order
      cosignatures, patient calls, results, and billable encounters. The report showed
      how often and for how long each activity was delinquent. We completed three Plan
      Do-Study-Act cycles. During cycle 1 (November to December 2015), we sent all
      providers automated e-mails with their monthly results. During cycle 2 (January
      to April 2016), we focused solely on billable encounter closure and sent targeted
      e-mails to providers with > 50 delinquent encounters. The e-mails stated that
      providers had 30 days to complete encounters or their practices would be closed
      to new patients; at 30 days, noncompliant providers had 60 days before practice
      suspension. During cycle 3 (May to September 2016), we continued to monitor and
      send targeted e-mails to providers who accumulated > 50 encounters. We modeled
      the financial impact of the intervention using net closure data, the report's
      aging function, and billing logs. RESULTS: InBasket monitoring with structured
      feedback decreased open encounters by 53.43%. We did not see improvements in the
      other metrics that the report tracked. We estimate that $231,724 was saved as a
      result of the intervention and $349,179 was lost to filing deadlines. CONCLUSION:
      Automated e-mails did not reduce open encounters; targeted e-mails to providers
      improved InBasket management.

PMID- 29641274
TI  - The number and function of T regulatory cells in obese atopic female asthmatics.
AB  - BACKGROUND: Mechanisms underlying the association between asthma and obesity
      remain poorly understood. Obesity appears to be a risk factor for asthma, and
      obese asthmatics fare poorly compared to lean asthmatics. OBJECTIVES: To explore
      the possibility that reduced regulatory T cell (Treg) number and function
      contribute to the obesity-asthma association. We concentrated on obese females
      with childhood-onset asthma, since Treg may be involved in this phenotype.
      METHODS: We recruited 64 women (ages 18-50) into four groups: lean (BMI 18-25
      kg/m2) controls (n = 17) and asthmatics (n = 13), and obese (BMI >= 35 kg/m2)
      controls (n = 17) and asthmatics (n = 17). Asthmatics had atopy and childhood
      diagnosed asthma. We assessed lung function, asthma control and quality of life.
      Peripheral blood CD4+/CD25+/FoxP3+ Treg cells were identified and counted by flow
      cytometry and expressed as % total CD4+ T cells. We assessed Treg cell function
      by the ability of CD4+/CD25+ Treg cells to suppress autologous CD4+/CD25-
      responder T cell (Tresp) proliferation and measured as % suppression of Tresp
      cell proliferation. RESULTS: Obese asthmatics had worse lung function, asthma
      control, and quality of life compared to lean asthmatics. Compared to lean or
      obese control groups, the number of Treg cells in the obese asthmatics was
      approximately 1.58- or 1.73-fold higher. The ability of Treg cells from obese
      asthmatics to suppress Tresp cell proliferation was reduced. CONCLUSIONS: Obese,
      atopic women with childhood diagnosed asthma demonstrate increased Treg cell
      number and mildly decreased Treg cell function. Our data do not support the view
      that reduced Treg cell number contributes to this obese-asthma phenotype.

PMID- 29641275
TI  - Development of a Pain Scoring System for Use in Sheep Surgically Implanted with
      Ventricular Assist Devices.
AB  - : Purpose/Aim: In prey species, such as sheep, clinical signs of postoperative
      pain can manifest in subtle ways or may be concealed entirely. Previous
      publications describing pain assessment in ruminants focus on lameness and flock
      behavior, often in a farm environment. These indicators of pain may be difficult
      to assess in sheep housed in biomedical research settings. We have developed a
      novel pain scoring system for sheep undergoing thoracotomy for implantation of
      ventricular assist devices that are permanently housed in modified stanchions.
      MATERIALS AND METHODS: The pain scoring system includes ruminant-specific
      behavioral signs of pain in addition to objective measurements that can be
      readily evaluated in a biomedical research setting. A numerical score is
      generated by the evaluator for each category. A decision tree is utilized to help
      guide further action following the generation of a cumulative score by the
      evaluator. A total score of 0-2 requires no intervention, 3-9 requires the
      consideration of additional analgesic administration, and a pain score >= 10
      warrants the consideration of additional multimodal analgesia. RESULTS: A novel
      pain scoring system and decision tree specifically designed for sheep undergoing
      thoracotomy in a biomedical research environment was developed and successfully
      utilized. Out of 102 postoperative pain scores measured, 86 scores were <2. There
      were 17/102 postoperative pain scores >=3, which typically resulted in the
      administration of supplemental rescue analgesia in the immediate postoperative
      period. CONCLUSIONS: A novel pain scoring system was developed and utilized in a
      biomedical research environment for evaluating postoperative pain in sheep
      undergoing thoracotomy for implantation of a ventricular assist device. Further
      studies are necessary to validate the reliability of this novel pain scoring
      system.

PMID- 29641276
TI  - A People-as-Means Approach to Interpersonal Relationships.
AB  - Interpersonal relationships and goal pursuit are intimately interconnected. In
      the present article, we present a people-as-means perspective on relationships.
      According to this perspective, people serve as means to goals-helping other
      people to reach their goals in a variety of ways, such as by contributing their
      time; lending their knowledge, skills, and resources; and providing emotional
      support and encouragement. Because people serve as means to goals, we propose
      that considering relationship processes in terms of the principles of goal
      pursuit can provide novel and important insights into the ways that people think,
      feel, and behave in these interpersonal contexts. We describe the principles of
      means-goals relations, review evidence for each principle involving people as
      means, and discuss implications of our approach for relationship formation,
      maintenance, and dissolution.

PMID- 29641277
TI  - Influenza vaccination coverage estimates in the fee-for service Medicare
      beneficiary population 2006 - 2016: Using population-based administrative data to
      support a geographic based near real-time tool.
AB  - Older adults are at great risk of developing serious complications from seasonal
      influenza. We explore vaccination coverage estimates in the Medicare population
      through the use of administrative claims data and describe a tool designed to
      help shape outreach efforts and inform strategies to help raise influenza
      vaccination rates. This interactive mapping tool uses claims data to compare
      vaccination levels between geographic (i.e., state, county, zip code) and
      demographic (i.e., race, age) groups at different points in a season. Trends can
      also be compared across seasons. Utilization of this tool can assist key actors
      interested in prevention - medical groups, health plans, hospitals, and state and
      local public health authorities - in supporting strategies for reaching pools of
      unvaccinated beneficiaries where general national population estimates of
      coverage are less informative. Implementing evidence-based tools can be used to
      address persistent racial and ethnic disparities and prevent a substantial number
      of influenza cases and hospitalizations.

PMID- 29641278
TI  - Respirator fit test methods - Are faster protocols equivalent to OSHA?

PMID- 29641279
TI  - Interview with Jean Bennett, MD, PhD.

PMID- 29641280
TI  - Gene Therapy Briefs.

PMID- 29641281
TI  - A Multicenter, Double-Blind, Phase III Clinical Trial to Evaluate the Efficacy
      and Safety of a Cell and Gene Therapy in Knee Osteoarthritis Patients.
AB  - The aim of this study was to test the clinical efficacy of TissueGene-C (TG-C), a
      cell and gene therapeutic for osteoarthritis consisting of non-transformed and
      transduced chondrocytes (3:1) retrovirally transduced to overexpress transforming
      growth factor-beta1. A total of 163 Kellgren-Lawrence grade 3 patients with knee
      osteoarthritis were randomly assigned to receive intra-articular TG-C or placebo.
      Primary efficacy measures included criteria for subjective assessment by
      International Knee Documentation Committee (IKDC) and pain severity by Visual
      Analog Scale (VAS) for 52 weeks. Secondary efficacy measures included IKDC and
      VAS at 26 and 39 weeks; pain, stiffness, and physical function by the Western
      Ontario and McMaster Universities Arthritis Index (WOMAC); and pain, symptoms,
      daily activities, function in sports and recreation, and quality of life by the
      Knee Injury and Osteoarthritis Outcome Score (KOOS), X-ray, magnetic resonance
      imaging, and soluble urine and blood biomarkers. TG-C was associated with
      statistically significant improvement over placebo in the total IKDC score and
      individual categories, and in the VAS score at 26, 39, and 52 weeks. WOMAC and
      KOOS scores also improved with TG-C over placebo. Patients treated with TG-C
      showed trends directed toward thicker cartilage and slower growing rates of
      subchondral bone surface area in the medial tibia, lateral tibia, lateral
      patella, and lateral patella femoral regions, although these were not
      statistically significant (p > 0.05). Serum C-terminal telopeptide of type I
      collagen (CTX-I) and urine CTX-II levels were lower over 1 year in TG-C than
      placebo-treated patients, with CTX-I level reaching statistical significance.
      These tendencies supported TG-C as holding great potential as a disease-modifying
      osteoarthritis drug. The most frequent adverse events in the TG-C group were
      peripheral edema (9%), arthralgia (8%), joint swelling (6%), and injection site
      pain (5%). TG-C was associated with statistically significant improvements in
      function and pain in patients with knee osteoarthritis. The unexpected adverse
      events were not observed.

PMID- 29641282
TI  - Associations of IL-1, 6, and 10 Gene Polymorphisms with Susceptibility to
      Recurrent Aphthous Stomatitis: Insights from a Meta-Analysis.
AB  - AIM: To determine if there are significant associations between polymorphisms of
      the IL-1, IL-6, and IL-10 genes and susceptibility to recurrent aphthous
      stomatitis (RAS). METHODS: The PubMed, Embase, and Web of Science databases were
      searched for all eligible studies using both medical subheadings and free terms
      through December 2016. A total of 226 citations were retrieved. Odds ratios were
      used to quantitatively evaluate the associations of IL-1, IL-6, and IL-10 gene
      polymorphisms with RAS risk. A meta-analysis was performed, and heterogeneity,
      sensitivity, and subgroup analyses were carried out to clarify and validate the
      pooled results. RESULTS: A total of 11 studies were identified that met the
      inclusion criteria and were included in the meta-analysis. This current
      systematic review indicated that the IL-1b+3954 C/T polymorphism was
      significantly associated with an elevated risk of RAS onset for all inheritance
      models, except for the dominant model. For the IL-10-592 C/A polymorphism,
      protective associations with RAS were found using both the additive and recessive
      models, while it increased the risk of RAS in the codominant model. In Asian
      populations, the IL-10-1082 G/A polymorphism was associated with a protective
      effect for RAS using the allelic, additive, and recessive models. The IL-6-174
      G/C polymorphism was not statistically associated with RAS risk. CONCLUSION: The
      IL-1b+3954 C/T polymorphism significantly increases RAS risk. In addition, the IL
      10-1082 G/A polymorphism provided protective effects for RAS in the Asian
      population.

PMID- 29641283
TI  - The Role of Dermcidin in the Diagnosis and Staging of Hepatocellular Carcinoma.
AB  - INTRODUCTION: Hepatocellular carcinoma (HCC) is a major contributor to cancer
      related deaths due to its often late stage diagnosis. Our previous study showed
      that dermcidin (DCD) may have the potential to be used as a serum biomarker for
      HCC for more timely diagnoses. MATERIALS AND METHODS: In this study, we measured
      serum DCD and alpha-fetoprotein (AFP) levels in 87 HCC patients; 33 liver
      cirrhosis (LC); and 44 normal controls (NC), evaluated the relationship between
      DCD levels and clinicopathological parameters. RESULTS: Serum DCD levels in HCC
      patients (27.03 ng/mL) were significantly higher than in LC patients (24.78
      ng/mL, p < 0.05), and NC subjects (18.98 ng/mL, p < 0.001). The optimum cutoff
      values were 25.75 ng/mL for DCD and 9.86 ng/mL for AFP. DCD had a greater area
      under the receiver operating characteristic curve (AUC) for differentiating HCC
      from the controls than AFP (AUC = 0.769 vs. 0.729, respectively). Importantly,
      our cohort revealed that serum DCD levels were positively correlated with
      metastasis in HCC patients versus HCC patients without metastatic disease (32.31
      vs. 23.95, p < 0.001). Western blot results showed that DCD expression was
      significantly upregulated in seven tumor tissues compared with the noncancerous
      adjacent tissues. Immunohistochemistry performed in four paired samples confirmed
      the upregulation of DCD expression in the tumor tissues. CONCLUSIONS: Our results
      showed that serum DCD levels were significantly increased in HCC patients and in
      cancerous tissue. DCD could potentially be used as a biomarker for the diagnosis
      of HCC.

PMID- 29641284
TI  - Personalized Dosing of Dichloroacetate Using GSTZ1 Clinical Genotyping Assay.
AB  - AIMS: Dichloroacetate (DCA) represents the first targeted therapy for pyruvate
      dehydrogenase complex deficiency; it is metabolized by glutathione transferase
      zeta1 (GSTZ1). Variation in the GSTZ1 haplotype is the principal variable
      influencing DCA kinetics and dynamics in humans. We aimed to develop a sensitive
      and rapid clinical genetic screening test for determining GSTZ1 haplotype status
      in individuals who would be treated with DCA, and then apply the test for the
      investigation of the plasma pharmacokinetics (PK) of DCA as a function of GSTZ1
      haplotype. MATERIALS AND METHODS: DNA samples from 45 healthy volunteer study
      participants were genotyped for three functional GSTZ1 single nucleotide
      polymorphisms (rs7975, rs7972, and rs1046428) by TaqMan(r). Prior studies showed
      that subjects with at least one EGT haplotype (EGT carrier) metabolized DCA
      faster than EGT noncarriers. The clinical genetic test for GSTZ1 was developed
      and validated at our CLIA-certified Clinical Laboratory. Four fast metabolizer
      EGT carriers and four slow metabolizer EGT noncarriers were selected to complete
      a standard PK study. Each participant received a single oral dose of 25 mg/kg of
      DCA (IND 028625) for 5 days. RESULTS: The EGT haplotype carrier group
      demonstrated significantly faster metabolism of DCA and higher rates of plasma
      DCA clearance after 5 days of drug exposure compared with EGT noncarriers (p =
      0.04). CONCLUSIONS: These preliminary data establish the validity and
      practicality of our rapid genotyping/haplotyping procedure for genetic-based DCA
      dosing to mitigate or prevent adverse effects in patients treated chronically
      with this drug.

PMID- 29641285
TI  - Deiodinases, Organic Anion Transporter Polypeptide Polymorphisms, and Thyroid
      Hormones in Patients with Myocardial Infarction.
AB  - AIM: To investigate the association among deiodinases (DIO), organic anion
      transporting polypeptide 1C1 (OATP1C1) gene polymorphisms, and thyroid hormones
      (THs) in patients with acute myocardial infarction (AMI). METHODS: In summary,
      290 patients with AMI were evaluated for sociodemographic and clinical
      characteristics, coronary artery disease (CAD) risk factors, and comorbidities,
      as well as circulating thyroid-stimulating hormone and TH (triiodothyronine [T3],
      thyroxine [T4], free T3, free T4, and reverse T3) levels. Ten single nucleotide
      polymorphisms for thyroid axis related genes: DIO1 (rs11206244-C/T, rs12095080
      A/G, rs2235544-A/C), DIO2 (rs225014-T/C, rs225015-G/A), DIO3 (rs945006-T/G), and
      OATP1C1 (rs10444412-T/C, rs10770704-C/T, rs1515777-A/G, rs974453-G/A) were
      genotyped. RESULTS: Marginal associations were observed between the DIO1, DIO2,
      and OATP1C1 gene polymorphisms and almost all analyzed THs (p's < 0.05). After
      controlling for potential confounders, the OATP1C1 rs1515777-A/G minor allele
      homozygous genotype (G/G) was associated with a decrease in circulating free T3
      and free T3/free T4. In the AMI cohort, associations between: DIO1 rs12095080 and
      hypertension; DIO2 rs225015 and diabetes mellitus; and the OATP1C1 rs974453
      genotype, and AMI type were established. CONCLUSIONS: DIO1 and DIO2 gene
      polymorphisms are mainly associated with T3, free T4, free T3/free T4, and
      [natural-log transformed (ln)] reverse T3 levels, while the OATP1C1 minor allele
      homozygous genotype is associated with free T3 and free T3/free T4 in CAD
      patients after AMI.

PMID- 29641286
TI  - Association of RETN and CAP1 SNPs, Expression and Serum Resistin Levels with
      Breast Cancer in Mexican Women.
AB  - BACKGROUND: Breast cancer is the most common cancer in women worldwide.
      Approximately 70% of female breast cancer patients have a body mass index (BMI)
      >25. In obesity, adipose tissue secretes additional resistin, which prompts a
      proinflammatory effect through its action on adenylate cyclase-associated protein
      1 (CAP1). Several studies have associated the RETN gene single nucleotide
      polymorphism (SNP) rs1862513 (-420C<G) with serum resistin levels and breast
      cancer. The CAP1 gene SNP rs35749351 (missense, Arg294His), located in the
      extracellular domain, has not previously been studied in cancer. These two SNPs,
      the mRNA expression levels of the two alleles for each of the cognate genes, and
      the serum resistin levels were compared between patients and controls to
      determine their association with breast cancer in Mexican women in this study.
      MATERIALS AND METHODS: This study included 308 controls and 100 female patients
      with breast cancer. SNPs were detected by PCR-RFLP from DNA isolated from
      peripheral blood. Gene expression was performed with hydrolysis probes in tumor
      tissue. Resistin levels were quantified from serum samples by ELISA. RESULTS: The
      RETN rs1862513CG/GG and CAP1 rs35749351GA/AA genotypes were associated with 1.61
      and 2.193-fold increased risks of breast cancer, respectively, compared with the
      CC and GG genotypes. Similarly, carriers of the G allele of rs1862513 and the A
      allele of rs35749351, had 1.51 and 2.217-fold increased risks of breast cancer
      compared with the C and G alleles, respectively. The rs1862513GG/rs35749351AA
      genotype combination increased breast cancer risk by twofold. Serum resistin
      levels in postmenopausal breast cancer women were higher compared with
      postmenopausal controls. Tissue CAP1 expression showed differences with regard to
      molecular subtypes and metastases. CONCLUSION: The RETN and CAP1 polymorphisms
      and gene expression may be potential biomarkers for breast cancer risk.

PMID- 29641288
TI  - Angiotensin II increases angiogenesis by NF-kappaB-mediated transcriptional
      activation of angiogenic factor AGGF1.
AB  - Angiogenic factor with G-patch and FHA domains 1 (AGGF1) is involved in vascular
      development, angiogenesis, specification of hemangioblasts, and differentiation
      of veins. When mutated, however, it causes Klippel-Trenaunay syndrome, a vascular
      disorder. In this study, we show that angiotensin II (AngII)-the major effector
      of the renin-angiotensin system and one of the most important regulators of the
      cardiovascular system-induces the expression of AGGF1 through NF-kappaB, and that
      AGGF1 plays a key role in AngII-induced angiogenesis. AngII significantly up
      regulated the levels of AGGF1 mRNA and protein in HUVECs at concentrations of 10
      40 MUg/ml but not >60 MUg/ml. AngII type 1 receptor (AT1R) inhibitor losartan
      inhibited AngII-induced up-regulation of AGGF1, whereas AT2R inhibitor PD123319
      further increased AngII-induced up-regulation of AGGF1. Up-regulation of AGGF1 by
      AngII was blocked by NF-kappaB inhibitors, and p65 binds directly to a binding
      site at the promoter/regulatory region of AGGF1 and transcriptionally activates
      AGGF1 expression. AngII-induced endothelial tube formation was blocked by small
      interfering RNAs (siRNAs) for RELA (RELA proto-oncogene, NF-kappaB subunit)/p65
      or AGGF1, and the effect of RELA siRNA was rescued by AGGF1. AngII-induced
      angiogenesis from aortic rings was severely impaired in Aggf1+/- mice, and the
      effect was restored by AGGF1. These data suggest that AngII acts as a critical
      regulator of AGGF1 expression through NF-kappaB, and that AGGF1 plays a key role
      in AngII-induced angiogenesis.-Si, W., Xie, W., Deng, W., Xiao, Y., Karnik, S.
      S., Xu, C., Chen, Q., Wang, Q. K. Angiotensin II increases angiogenesis by NF
      kappaB-mediated transcriptional activation of angiogenic factor AGGF1.

PMID- 29641289
TI  - Executive Function Computerized Training in Very Preterm-Born Children: A Pilot
      Study.
AB  - OBJECTIVE: Attention problems are one of the most pronounced and documented
      consequences of very preterm birth (gestational age <=32 weeks). However, up to
      now, there is no research published on suitable interventions at school age aimed
      to overcome these problems. Research in this population did show that executive
      functions (EFs) are strongly associated with inattention. BrainGame Brian is a
      newly developed computerized training, in which, in 25 training sessions, the
      core EFs, including working memory, impulse control, and cognitive flexibility,
      are trained. This pilot study aimed to examine the feasibility of studying
      BrainGame Brian in very preterm-born children with attention problems. DESIGN:
      Pilot feasibility intervention study with one baseline and one follow-up
      assessment. MATERIALS AND METHODS: Feasibility was measured by the participation
      rate, dropout rate, and user experiences with regard to effort, training
      characteristics, and recommendation to others. From a larger cohort study, 15
      very preterm-born children at age 10 years with parent-reported attention
      problems on the Child Behavior Checklist/6-18 years were invited to participate
      in this pilot study. BrainGame Brian was performed for a period of 6 weeks.
      Training outcome measures included visual working memory, impulse control,
      cognitive flexibility, speed variability, and parent-rated attention, for which
      pre- and post-training differences were examined at the group level by the
      Wilcoxon signed-rank test as well as for each individual child separately by the
      reliable change index. RESULTS: Twelve of 15 children and their parents agreed to
      participate and 11 children successfully completed BrainGame Brian in the 6-week
      period. Parents were positive about training characteristics and lack of
      interference with schooling, but scored the effort as high. We found clinically
      significant changes in visual working memory and speed variability in post
      training assessments. CONCLUSION: BrainGame Brian is a feasible intervention for
      very preterm-born children with attention problems.

PMID- 29641290
TI  - From infancy and beyond... ensuring a lifetime of hepatitis B virus (HBV) vaccine
      induced immunity.
AB  - Despite the long-term efficacy and immune persistence observed following HBV
      vaccination of infants, the need for a booster dose following infant immunization
      continues to be deliberated. Evidence from HBV booster dose response studies and
      long-term immunization program reviews are the basis for the recommendation that
      a vaccine booster is not necessary. However, further studies continue to emerge
      and highlight the need for standardization among observational studies in order
      to appropriately compare outcomes. There is an assumption that neonatal and
      infant (within 12 months of age) vaccine immune responses are equivalent;
      however, evidence exists for distinct vaccine responses within the first year of
      life. HBV vaccine programs have evolved over time, particularly regarding the
      type and dosage of vaccine used. Several universal neonatal immunization programs
      initially incorporated a 2.5 MUg dosage (Recombivax-HB, Merck). This dosage has
      been shown in multiple long-term studies and meta-analyses to be associated with
      a lower primary response, decreased antibody persistence over time, and a reduced
      booster response 10 to 20 years following immunization. Ongoing surveillance of
      this and other HBV neonatally-vaccinated populations, particularly in low endemic
      regions, is necessary to understand the impact on long-term protection in order
      to ensure lifelong protection against hepatitis B infection.

PMID- 29641292
TI  - The association between asthma and obstructive sleep apnea (OSA): A systematic
      review.
AB  - OBJECTIVE: Bronchial asthma and obstructive sleep apnoea (OSA) are common
      respiratory disorders that can co-exist. The strength of this association, and
      also the impact of OSA on asthma-related clinical outcomes remain unclear. DATA
      SOURCES: Literature review was performed in EMBASE and MEDLINE databases. Studies
      up to and including 2016 were selected. STUDY SELECTION: Studies were included if
      they contained; 1) a population with asthma AND 2) a prevalence of OSA reported
      using either polysomnography or validated questionnaires such as the Sleep Apnoea
      Scale of the Sleep Disorders Questionnaire (SA-SDQ), STOP BANG or the Berlin
      questionnaire. RESULTS: Nineteen studies were identified. Thirteen questionnaire
      based studies met the inclusion/exclusion criteria and twelve of these
      demonstrated a prevalence of OSA in asthma of 8-52.6%, with one study showing no
      association between the two conditions. Six studies using polysomnography
      demonstrated a high prevalence of 19.2-60%; which was higher at 50-95% in severe
      asthma. Two polysomnography and four questionnaire studies found worse asthma
      related clinical outcomes with co-existing OSA. One polysomnography and two
      questionnaire studies showed no difference. CONCLUSION: This systematic review
      suggests that there is a high prevalence of OSA in asthma, particularly within
      severe asthma populations and that co-diagnosis of OSA in asthma patients is
      associated with worse clinical outcomes. However this outcome was not uniform and
      the number of studies using polysomnography to confirm OSA was small. This
      weakens the conclusions that can be drawn and prompts the need for adequately
      powered and well-designed studies to confirm or refute these findings.

PMID- 29641291
TI  - Sex differences in daily life stress and craving in opioid-dependent patients.
AB  - BACKGROUND: Responses to stress and drug craving differ between men and women.
      Differences in the momentary experience of stress in relation to craving are less
      well-understood. OBJECTIVES: Using ecological momentary assessment (EMA), we
      examined sex differences in real-time in two areas: (1) causes and contexts
      associated with stress, and (2) the extent to which stress and drug cues are
      associated with craving. METHODS: Outpatients on opioid-agonist treatment (135
      males, 47 females) reported stress, craving, and behavior on smartphones for 16
      weeks. They initiated an entry each time they felt more stressed than usual
      (stress event) and made randomly prompted entries 3 times/day. In stress-event
      entries, they identified the causes and context (location, activity, companions),
      and rated stress and craving severity. RESULTS: The causes reported for stress
      events did not differ significantly by sex. Women reported arguing and being in a
      store more often during stress events, and men reported working more often during
      stress events, compared to base rates (assessed via random prompts). Women showed
      a greater increase in opioid craving as a function of stress (p < 0.0001) and had
      higher stress ratings in the presence of both stress and drug cues relative to
      men (p < 0.01). Similar effects were found for cocaine craving in men (p <
      0.0001). CONCLUSION: EMA methods provide evidence based on real-time activities
      and moods that opioid-dependent men and women experience similar contexts and
      causes for stress but differ in stress- and cue-induced craving. These findings
      support sex-based tailoring of treatment, but because not all participants
      conformed to the overall pattern of sex differences, any such tailoring should
      also consider person-level differences.

PMID- 29641293
TI  - Integrated BioTherapeutics.

PMID- 29641294
TI  - Adaptive Servoventilation as Treatment for Central Sleep Apnea Due to High
      Altitude Periodic Breathing in Nonacclimatized Healthy Individuals.
AB  - : Orr, Jeremy E., Erica C. Heinrich, Matea Djokic, Dillon Gilbertson, Pamela N.
      Deyoung, Cecilia Anza-Ramirez, Francisco C. Villafuerte, Frank L. Powell, Atul
      Malhotra, and Tatum Simonson. Adaptive servoventilation as treatment for central
      sleep apnea due to high-altitude periodic breathing in nonacclimatized healthy
      individuals. High Alt Med Biol. 19:178-184, 2018. AIMS: Central sleep apnea (CSA)
      is common at high altitude, leading to desaturation and sleep disruption. We
      hypothesized that noninvasive ventilation using adaptive servoventilation (ASV)
      would be effective at stabilizing CSA at altitude. Supplemental oxygen was
      evaluated for comparison. METHODS: Healthy subjects were brought from sea level
      to 3800 m and underwent polysomnography on three consecutive nights. Subjects
      underwent each condition-No treatment, ASV, and supplemental oxygen-in random
      order. The primary outcome was the effect of ASV on oxygen desaturation index
      (ODI). Secondary outcomes included oxygen saturation, arousals, symptoms, and
      comparison to supplemental oxygen. RESULTS: Eighteen subjects underwent at least
      two treatment conditions. There was a significant difference in ODI across the
      three treatments. There was no statistical difference in ODI between no treatment
      and ASV (17.1 +/- 4.2 vs. 10.7 +/- 2.9 events/hour; p > 0.17) and no difference
      in saturation or arousal index. Compared with no treatment, oxygen improved the
      ODI (16.5 +/- 4.5 events/hour vs. 0.5 +/- 0.2 events/hour; p < 0.003), in
      addition to saturation and arousal index. CONCLUSIONS: We found that ASV was not
      clearly efficacious at controlling CSA in persons traveling to 3800 m, whereas
      supplemental oxygen resolved CSA. Adjustment in the ASV algorithm may improve
      efficacy. ASV may have utility in acclimatized persons or at more modest
      altitudes.

PMID- 29641296
TI  - Postmarketing Modifications of Drug Labels for Cancer Drugs Approved by the US
      Food and Drug Administration Between 2006 and 2016 With and Without Supporting
      Randomized Controlled Trials.
AB  - Purpose Modifications in cancer drug indications, dosing, and related toxicities
      after Food and Drug Administration approval are common. It is unclear whether
      drug approval without a supporting randomized controlled trial (RCT) influences
      the probability of such modifications. Methods We searched the Drugs@FDA Web site
      for new drug indications for solid tumors approved between January 2006 and
      December 2016. Study characteristics, regulatory pathways, and label
      modifications from approval to October 2017 were collected from drug labels.
      Label modifications were considered to be major if defined as such in the drug
      label. Indications approved with and without supporting RCTs were compared using
      logistic regression. The Benjamini-Hochberg false discovery rate method was used
      to adjust for multiplicity. Results We identified 59 individual drugs for 109
      solid tumor indications. Of these, 17 indications (15.6%) were not supported by
      an RCT, with no change over time. Indications not supported by RCTs were more
      likely to require companion diagnostic tests (odds ratio [OR], 3.90; P = .02), to
      include surrogate end points as primary outcomes (OR, 7.88; P < .001), and to
      receive breakthrough therapy designation (OR, 7.62; P = .006) or accelerated
      approval (OR, 17.67; P < .001). Indications not supported by RCTs were associated
      with significantly higher odds of postapproval modifications in common adverse
      events (71% v 29%; OR, 5.78; P = .002). A nonsignificantly higher odds of
      postapproval major modifications in warnings and precautions was also observed
      (88% v 62%; OR, 4.61; P = .051). Postapproval major modifications in indication
      and usage, dosing and administration, boxed warnings, and contraindications were
      comparable in the two groups. Conclusion Cancer drug indications not supported
      initially by RCTs are associated with more postmarketing safety-related label
      modifications. Health care professionals should be vigilant for unrecognized
      adverse effects when prescribing drugs approved without a supporting RCT.

PMID- 29641295
TI  - Electronic Nose Technology Fails to Sniff Out Acute Mountain Sickness.
AB  - : Berendsen, Remco R., Marieke E. van Vessem, Marcel Bruins, Luc J.S.M. Teppema,
      Leon P.H.J. Aarts, and Bengt Kayser. Electronic nose technology fails to sniff
      out acute mountain sickness. High Alt Med Biol. 19:232-236, 2018. AIM: The aim of
      the study was to evaluate whether an electronic nose can discriminate between
      individuals with and without acute mountain sickness (AMS) following rapid ascent
      to 4554 m. RESULTS: We recruited recreational climbers (19 women, 82 men; age 35
      +/- 10 years, mean +/- standard deviation [SD]) upon arrival at 4554 m (Capanna
      Regina Margherita, Italy) for a proof of concept study. AMS was assessed with the
      Lake Louise self-report score (LLSRS) and the abbreviated Environmental Symptoms
      Questionnaire (ESQc); scores >=3 and >=0.7 were considered AMS, respectively.
      Exhaled air was analyzed with an electronic nose (Aeonose; The eNose Company,
      Netherlands). The collected data were analyzed using an artificial neural
      network. AMS prevalence was 44% with the LLSRS (mean score of those sick 4.4 +/-
      1.4 [SD]) and 20% with the ESQc (1.2 +/- 0.5). The electronic nose could not
      discriminate between AMS and no AMS (LLSRS p = 0.291; ESQc p = 0.805).
      CONCLUSION: The electronic nose technology utilized in this study could not
      discriminate between climbers with and without symptoms of AMS in the setting of
      an acute exposure to an altitude of 4554 m. At this stage, we cannot fully
      exclude that this technology per se is not able to discriminate for AMS. The
      quest for objective means to diagnose AMS thus continues.

PMID- 29641297
TI  - Phase II Study of Two Weeks on, One Week off Sunitinib Scheduling in Patients
      With Metastatic Renal Cell Carcinoma.
AB  - Purpose Standard frontline treatment of patients with metastatic renal cell
      carcinoma currently includes sunitinib. A barrier to long-term treatment with
      sunitinib includes the development of significant adverse effects, including
      diarrhea, hand-foot syndrome (HFS), and fatigue. This trial assessed the effect
      of an alternate 2 weeks on, 1 week off (2/1) schedule of sunitinib on toxicity
      and efficacy in previously untreated patients with metastatic renal cell
      carcinoma. Methods Patients started with oral administration of 50 mg sunitinib
      on a 2/1 schedule and underwent schedule and dose alterations if toxicity
      developed. The primary end point was < 15% grade >= 3 fatigue, diarrhea, or HFS.
      With 60 patients, the upper bound of the CI would fall below the published 4/2
      schedule grade >= 3 toxicity rate of 25% to 30%. Results Fifty-nine patients were
      treated between August 2014 and March 2016. Seventy-seven percent were
      intermediate or poor risk per Memorial Sloan Kettering Cancer Center criteria.
      With a median follow-up of 17 months, 25% of patients experienced grade 3
      fatigue, HFS, or diarrhea; 37% required a dose reduction, and 10% discontinued
      because of toxicity. The overall response rate was 57%, median progression-free
      survival was 13.7 months, and median overall survival was not reached. At 12
      weeks, Functional Assessment of Cancer Therapy-General scores dropped between 0%
      and 10% from baseline, with less reduction in patients who continued treatment
      longer. Conclusion The primary end point of decreased grade 3 toxicity was not
      met; however, treatment with a 2/1 sunitinib schedule is associated with a lack
      of grade 4 toxicity, a low patient discontinuation rate, and high efficacy.

PMID- 29641298
TI  - Correction to: Recent Progress on Genetic Diagnosis and Therapy for beta
      Thalassemia in China and Around the World, by Zhang J, Yan J, and Zeng F. Hum
      Gene Ther 2018;29(2):197-203. DOI: 10.1089/hum.2017.228.

PMID- 29641299
TI  - Temporal exploration in sequential movements shapes efficient neuromuscular
      control.
AB  - The interaction of early and deliberate practice with genetic predisposition
      endows experts with virtuosic motor performance. However, it has not been known
      whether ways of practicing shape motor virtuosity. Here, we addressed this issue
      by comparing the effects of rhythmic variation in motor practice on neuromuscular
      control of the finger movements in pianists. With the use of a novel
      electromyography system with miniature active electrodes, we recorded the
      activity of the intrinsic hand muscles of 27 pianists while they played the piano
      and analyzed it by using a nonnegative matrix factorization algorithm and cluster
      analysis. The result demonstrated that practicing a target movement sequence with
      various rhythms reduced muscular activity, whereas neither practicing a sequence
      with a single rhythm nor taking a rest without practicing changed the activity.
      In addition, practice with rhythmic variation changed the patterns of
      simultaneous activations across muscles. This alteration of muscular coordination
      was associated with decreased activation of muscles not only relevant to, but
      also irrelevant to the task performance. In contrast, piano practice improved the
      maximum speed of the performance, the amount of which was independent of whether
      rhythmic variation was present. These results suggest that temporal variation in
      movement sequences during practice co-optimizes both movement speed and
      neuromuscular efficiency, which emphasizes the significance of ways of practice
      in the acquisition of motor virtuosity. NEW & NOTEWORTHY A key question in motor
      neuroscience is whether "ways of practicing" contribute to shaping motor
      virtuosity. We found both attenuation of activities and alteration of
      coordination of the intrinsic hand muscles of pianists, specifically through
      practicing a movement sequence with various rhythms. The maximum speed of the
      finger movements was also enhanced following the practice. These results
      emphasize the importance of ways of practicing in facilitating multiple skills:
      efficiency and speed.

PMID- 29641301
TI  - State anxiety disorganizes finger movements during musical performance.
AB  - Skilled performance, in many situations, exposes an individual to psychological
      stress and fear, thus triggering state anxiety and compromising motor dexterity.
      Suboptimal skill execution in people under pressure affects the future career
      prospects of trained individuals, such as athletes, clinicians, and musicians.
      However, it has not been elucidated in what manner state anxiety affects
      multijoint movements and thereby degrades fine motor control. Using principal
      component analysis of hand kinematics recorded by a data glove during piano
      performances, we tested whether state anxiety affects the organization of
      movements of multiple joints or merely constrains the amplitude of the individual
      joints without affecting joint movement coordination. The result demonstrated
      changes in the coordination of movements across joints in piano performances by
      experts under psychological stress. Overall, the change was characterized by
      reduction of synergistic movements between the finger responsible for the
      keypress and its adjacent fingers. A regression analysis further identified that
      the attenuation of the movement covariation between the fingers was associated
      with an increase in temporal error during performance under pressure. In
      contrast, neither the maximum nor minimum angles of the individual joints of the
      hand were susceptible to induced anxiety. These results suggest that degradation
      of fine motor control under pressure is mediated by incoordination of movements
      between the fingers in skilled piano performances. NEW & NOTEWORTHY A key issue
      in neuromuscular control of coordinated movements is how the nervous system
      organizes multiple degrees of freedom for production of skillful motor behaviors.
      We found that state anxiety disorchestrates the organization of finger movements
      so as to decrease synergistic motions between the fingers in musical performance,
      which degrades fine motor control. The findings are important to shed light on
      mechanisms underlying loss of motor dexterity under pressure.

PMID- 29641302
TI  - High-definition transcranial direct-current stimulation of the right M1 further
      facilitates left M1 excitability during crossed facilitation.
AB  - Cabibel et al. (J Neurophysiol 119: 1266-1272, 2018) report non-polarity-specific
      effects of high-definition direct current stimulation (HD-tDCS) on crossed
      facilitation (CF), demonstrated by complex excitatory and inhibitory
      interhemispheric interactions coupled with HD-tDCS. Choosing a variety of
      stimulation and muscle contraction parameters and having all participants undergo
      anodal, cathodal, and sham stimulation may increase the current understanding of
      HD-tDCS on CF. Furthermore, complementary metrics like the ipsilateral silent
      period may provide more clarity regarding the polarity-specific enhancement of HD
      tDCS on CF.

PMID- 29641303
TI  - Multisensory enhancement of burst activity in an insect auditory neuron.
AB  - Detecting predators is crucial for survival. In insects, a few sensory
      interneurons receiving sensory input from a distinct receptive organ extract
      specific features informing the animal about approaching predators and mediate
      avoidance behaviors. Although integration of multiple sensory cues relevant to
      the predator enhances sensitivity and precision, it has not been established
      whether the sensory interneurons that act as predator detectors integrate
      multiple modalities of sensory inputs elicited by predators. Using intracellular
      recording techniques, we found that the cricket auditory neuron AN2, which is
      sensitive to the ultrasound-like echolocation calls of bats, responds to airflow
      stimuli transduced by the cercal organ, a mechanoreceptor in the abdomen. AN2
      enhanced spike outputs in response to cross-modal stimuli combining sound with
      airflow, and the linearity of the summation of multisensory integration depended
      on the magnitude of the evoked response. The enhanced AN2 activity contained
      bursts, triggering avoidance behavior. Moreover, cross-modal stimuli elicited
      larger and longer lasting excitatory postsynaptic potentials (EPSP) than unimodal
      stimuli, which would result from a sublinear summation of EPSPs evoked
      respectively by sound or airflow. The persistence of EPSPs was correlated with
      the occurrence and structure of burst activity. Our findings indicate that AN2
      integrates bimodal signals and that multisensory integration rather than unimodal
      stimulation alone more reliably generates bursting activity. NEW & NOTEWORTHY
      Crickets detect ultrasound with their tympanum and airflow with their cercal
      organ and process them as alert signals of predators. These sensory signals are
      integrated by auditory neuron AN2 in the early stages of sensory processing.
      Multisensory inputs from different sensory channels enhanced excitatory
      postsynaptic potentials to facilitate burst firing, which could trigger avoidance
      steering in flying crickets. Our results highlight the cellular basis of
      multisensory integration in AN2 and possible effects on escape behavior.

PMID- 29641300
TI  - Development, form, and function of the mouse visual thalamus.
AB  - The dorsal lateral geniculate nucleus (dLGN) of the thalamus is the exclusive
      relay of retinal information en route to the visual cortex. Although much of our
      understanding about dLGN comes from studies done in higher mammals, such as the
      cat and primate, the mouse as a model organism has moved to the forefront as a
      tractable experimental platform to examine cell type-specific relations. This
      review highlights our current knowledge about the development, structure, and
      function of the mouse dLGN.

PMID- 29641305
TI  - Happy 80th birthday to the Journal of Neurophysiology!

PMID- 29641304
TI  - Contextual modulation of sensitivity to naturalistic image structure in macaque
      V2.
AB  - The stimulus selectivity of neurons in V1 is well known, as is the finding that
      their responses can be affected by visual input to areas outside of the classical
      receptive field. Less well understood are the ways selectivity is modified as
      signals propagate to visual areas beyond V1, such as V2. We recently proposed a
      role for V2 neurons in representing the higher order statistical dependencies
      found in images of naturally occurring visual texture. V2 neurons, but not V1
      neurons, respond more vigorously to "naturalistic" images that contain these
      dependencies than to "noise" images that lack them. In this work, we examine the
      dependency of these effects on stimulus size. For most V2 neurons, the preference
      for naturalistic over noise stimuli was modest when presented in small patches
      and gradually strengthened with increasing size, suggesting that the mechanisms
      responsible for this enhanced sensitivity operate over regions of the visual
      field that are larger than the classical receptive field. Indeed, we found that
      surround suppression was stronger for noise than for naturalistic stimuli and
      that the preference for large naturalistic stimuli developed over a delayed time
      course consistent with lateral or feedback connections. These findings are
      compatible with a spatially broad facilitatory mechanism that is absent in V1 and
      suggest that a distinct role for the receptive field surround emerges in V2 along
      with sensitivity for more complex image structure. NEW & NOTEWORTHY The responses
      of neurons in visual cortex are often affected by visual input delivered to
      regions of the visual field outside of the conventionally defined receptive
      field, but the significance of such contextual modulations are not well
      understood outside of area V1. We studied the importance of regions beyond the
      receptive field in establishing a novel form of selectivity for the statistical
      dependencies contained in natural visual textures that first emerges in area V2.

PMID- 29641307
TI  - Somatosensory electrical stimulation improves skill acquisition, consolidation,
      and transfer by increasing sensorimotor activity and connectivity.
AB  - The interaction between the somatosensory and motor systems is important for
      normal human motor function and learning. Enhancing somatosensory input using
      somatosensory electrical stimulation (SES) can increase motor performance, but
      the neuronal mechanisms underlying these effects are largely unknown. With EEG,
      we examined whether skill acquisition, consolidation, and interlimb transfer
      after SES was related to increased activity in sensorimotor regions, as assessed
      by the N30 somatosensory evoked potential or rather increased connectivity
      between these regions, as assessed by the phase slope index (PSI). Right- and
      left-hand motor performance and EEG measures were taken before, immediately
      after, and 24 h ( day 2) after either SES ( n = 12; 5 men) or Control ( n = 12; 5
      men). The results showed skill acquisition and consolidation in the stimulated
      right hand immediately after SES (6%) and on day 2 (9%) and interlimb transfer to
      the nonstimulated left hand on day 2 relative to Control (8%, all P < 0.05).
      Increases in N30 amplitudes correlated with skill acquisition while PSI from
      electrodes that represent the posterior parietal and primary somatosensory cortex
      to the electrode representing the primary motor cortex correlated with skill
      consolidation. In contrast, interlimb transfer did not correlate with the EEG
      derived neurophysiological estimates obtained in the present study, which may
      indicate the involvement of subcortical structures in interlimb transfer after
      SES. In conclusion, weak peripheral somatosensory inputs in the form of SES
      improve skill acquisition, consolidation, and interlimb transfer that coincide
      with different cortical adaptations, including enhanced N30 amplitudes and PSI.
      NEW & NOTEWORTHY The relationship between adaptations in synaptic plasticity and
      motor learning following somatosensory electrical stimulation (SES) is
      incompletely understood. Here, we used for the first time a multifactorial
      approach that examined skill acquisition, consolidation, and interlimb transfer
      following 20 min of SES. In addition, we quantified sensorimotor integration and
      the magnitude and direction of connectivity with EEG. Following artificial
      electrical stimulation, increases in sensorimotor integration and connectivity
      were found to correlate with skill acquisition and consolidation, respectively.

PMID- 29641306
TI  - Functional roles of Kv1-mediated currents in genetically identified subtypes of
      pyramidal neurons in layer 5 of mouse somatosensory cortex.
AB  - We used voltage-clamp recordings from somatic outside-out macropatches to
      determine the amplitude and biophysical properties of putative Kv1-mediated
      currents in layer 5 pyramidal neurons (PNs) from mice expressing EGFP under the
      control of promoters for etv1 or glt. We then used whole cell current-clamp
      recordings and Kv1-specific peptide blockers to test the hypothesis that Kv1
      channels differentially regulate action potential (AP) voltage threshold,
      repolarization rate, and width as well as rheobase and repetitive firing in these
      two PN types. We found that Kv1-mediated currents make up a similar percentage of
      whole cell K+ current in both cell types, and only minor biophysical differences
      were observed between PN types or between currents sensitive to different Kv1
      blockers. Putative Kv1 currents contributed to AP voltage threshold in both PN
      types, but AP width and rate of repolarization were only affected in etv1 PNs.
      Kv1 currents regulate rheobase, delay to the first AP, and firing rate similarly
      in both cell types, but the frequency-current slope was much more sensitive to
      Kv1 block in etv1 PNs. In both cell types, Kv1 block shifted the current required
      to elicit an onset doublet of action potentials to lower currents. Spike
      frequency adaptation was also affected differently by Kv1 block in the two PN
      types. Thus, despite similar expression levels and minimal differences in
      biophysical properties, Kv1 channels differentially regulate APs and repetitive
      firing in etv1 and glt PNs. This may reflect differences in subcellular
      localization of channel subtypes or differences in the other K+ channels
      expressed. NEW & NOTEWORTHY In two types of genetically identified layer 5
      pyramidal neurons, alpha-dendrotoxin blocked approximately all of the putative
      Kv1 current (on average). We used outside-out macropatches and whole cell
      recordings at 33 degrees C to show that despite similar expression levels and
      minimal differences in biophysical properties, Kv1 channels differentially
      regulate action potentials and repetitive firing in etv1 and glt pyramidal
      neurons. This may reflect differences in subcellular localization of channel
      subtypes or differences in the other K+ channels expressed.

PMID- 29641308
TI  - Action potential propagation recorded from single axonal arbors using
      multielectrode arrays.
AB  - We report the presence of co-occurring extracellular action potentials (eAPs)
      from cultured mouse hippocampal neurons among groups of planar electrodes on
      multielectrode arrays (MEAs). The invariant sequences of eAPs among coactive
      electrode groups, repeated co-occurrences, and short interelectrode latencies are
      consistent with action potential propagation in unmyelinated axons. Repeated eAP
      codetection by multiple electrodes was widespread in all our data records.
      Codetection of eAPs confirms they result from the same neuron and allows these
      eAPs to be isolated from all other spikes independently of spike sorting
      algorithms. We averaged co-occurring events and revealed additional electrodes
      with eAPs that would otherwise be below detection threshold. We used these eAP
      cohorts to explore the temperature sensitivity of action potential propagation
      and the relationship between voltage-gated sodium channel density and propagation
      velocity. The sequence of eAPs among coactive electrodes "fingerprints" neurons
      giving rise to these events and identifies them within neuronal ensembles. We
      used this property and the noninvasive nature of extracellular recording to
      monitor changes in excitability at multiple points in single axonal arbors
      simultaneously over several hours, demonstrating independence of axonal segments.
      Over several weeks, we recorded changes in interelectrode propagation latencies
      and ongoing changes in excitability in different regions of single axonal arbors.
      Our work illustrates how repeated eAP co-occurrences can be used to extract
      physiological data from single axons with low-density MEAs. However, repeated eAP
      co-occurrences lead to oversampling spikes from single neurons and thus can
      confound traditional spike-train analysis. NEW & NOTEWORTHY We studied action
      potential propagation in single axons using low-density multielectrode arrays. We
      unambiguously identified the neuronal sources of propagating action potentials
      and recorded extracellular action potentials from several positions within single
      axonal arbors. We found a surprisingly high density of axonal voltage-gated
      sodium channels responsible for a high propagation safety factor. Our experiments
      also demonstrate that excitability in different segments of single axons is
      regulated independently on timescales from hours to weeks.

PMID- 29641309
TI  - The caudal fastigial nucleus and the steering of saccades toward a moving visual
      target.
AB  - The caudal fastigial nuclei (cFN) are the output nuclei by which the medio
      posterior cerebellum influences the production of visual saccades. We
      investigated in two head-restrained monkeys their contribution to the generation
      of interceptive saccades toward a target moving centrifugally by analyzing the
      consequences of a unilateral inactivation (10 injection sessions). We describe
      here the effects on saccades made toward a centrifugal target that moved along
      the horizontal meridian with a constant (10, 20, or 40 degrees /s), increasing
      (from 0 to 40 degrees /s over 600 ms), or decreasing (from 40 to 0 degrees /s
      over 600 ms) speed. After muscimol injection, the monkeys were unable to foveate
      the current location of the moving target. The horizontal amplitude of
      interceptive saccades was reduced during contralesional target motions and
      hypermetric during ipsilesional ones. For both contralesional and ipsilesional
      saccades, the magnitude of dysmetria increased with target speed. However, the
      use of accelerating and decelerating targets revealed that the dependence of
      dysmetria upon target velocity was not due to the current velocity but to the
      required amplitude of saccade. We discuss these results in the framework of two
      hypotheses, the so-called "dual drive" and "bilateral" hypotheses. NEW &
      NOTEWORTHY Unilateral inactivation of the caudal fastigial nucleus impairs the
      accuracy of saccades toward a moving target. Like saccades toward a static
      target, interceptive saccades are hypometric when directed toward the
      contralesional side and hypermetric when they are ipsilesional. The dysmetria
      depends on target velocity, but the use of accelerating or decelerating targets
      reveals that velocity is not the crucial parameter. We extend the bilateral
      fastigial control of saccades and fixation to the production of interceptive
      saccades.

PMID- 29641311
TI  - Asymmetric interference between cognitive task components and concurrent
      sensorimotor coordination.
AB  - Everyday cognitive tasks are frequently performed under dual-task conditions
      alongside continuous sensorimotor coordinations (CSCs) such as driving, walking,
      or balancing. Observed interference in these dual-task settings is commonly
      attributed to demands on executive function or attentional resources, but the
      time course and reciprocity of interference are not well understood at the level
      of information-processing components. Here we used electrophysiology to study the
      detailed chronometry of dual-task interference between a visual oddball task and
      a continuous visuomanual tracking task. The oddball task's electrophysiological
      components were linked to underlying cognitive processes, and the tracking task
      served as a proxy for the continuous cycle of state monitoring and adjustment
      inherent to CSCs. Dual-tasking interfered with the oddball task's accuracy and
      attentional processes (attenuated P2 and P3b magnitude and parietal alpha-band
      event-related desynchronization), but errors in tracking due to dual-tasking
      accrued at a later timescale and only in trials in which the target stimulus
      appeared and its tally had to be incremented. Interference between cognitive
      tasks and CSCs can be asymmetric in terms of timing as well as affected
      information-processing components. NEW & NOTEWORTHY Interference between
      cognitive tasks and continuous sensorimotor coordination (CSC) has been widely
      reported, but this is the first demonstration that the cognitive operation that
      is impaired by concurrent CSC may not be the one that impairs the CSC. Also
      demonstrated is that interference between such tasks can be temporally
      asymmetric. The asynchronicity of this interference has significant implications
      for understanding and mitigating loss of mobility in old age, and for
      rehabilitation for neurological impairments.

PMID- 29641310
TI  - Effects of a compression garment on sensory feedback transmission in the human
      upper limb.
AB  - Compression apparel is popular in both medical and sport performance settings.
      Perceived benefits are suggested to include changes in sensory feedback
      transmission caused by activation of mechanoreceptors. However, little is known
      about effects of compression apparel on sensorimotor control. Our purpose was to
      mechanistically examine whether compression apparel modulates sensory feedback
      transmission and reaching accuracy in the upper limb. Two experiments were
      completed under CONTROL and COMPRESSION (sleeve applied across the elbow joint)
      conditions. M-waves and H-reflexes were elicited by stimulating the median nerve
      and were recorded via surface electromyography (EMG). In experiment 1, H-reflexes
      and M-H recruitment curves were assessed at REST, during wrist flexion (10%
      EMGmax), and during a cutaneous conditioning of the superficial radial (SR) or
      distal median (MED) nerve. Cutaneous reflexes were elicited during 10% wrist
      flexion via stimulation of SR or MED. In experiment 2, unconditioned H-reflex
      measures were assessed at rest, during arm cycling, and during a discrete
      reaching task. Results indicate that compression apparel modulates spinal cord
      excitability across multiple sensory pathways and movement tasks. Interestingly,
      there was a significant improvement in reaching accuracy while wearing the
      compression sleeve. Taken together, the compression sleeve appears to increase
      precision and sensitivity around the joint where the sleeve is applied.
      Compression apparel may function as a "filter" of irrelevant mechanoreceptor
      information allowing for optimal task-related sensory information to enhance
      proprioception. NEW & NOTEWORTHY Wearing a customized compression sleeve was
      shown to alter the excitability of multiple pathways within the central nervous
      system regardless of conditioning input or movement task and was accompanied by
      improved accuracy of reaching movements and determination of movement end point.
      Compression apparel may assist as a type of "filter function" of tonic and
      nonspecific mechanoreceptor information leading to increased precision and
      movement sensitivity around the joint where compression is applied.

PMID- 29641312
TI  - The Future LGBT Health Professional: Perspectives on Career and Personal
      Mentorship.
AB  - PURPOSE: Mentorship is a critical factor contributing to career success. There is
      limited research on the quality of mentoring relationships for LGBT health
      professionals. This study explores facilitators of, obstacles to, and strategies
      for successful mentorship for LGBT health professional trainees. METHODS: We
      applied a convenience sampling strategy to collect quantitative and qualitative
      data among LGBT health professional trainees. The authors identified trends in
      data using bivariate analyses and Consensual Qualitative Research methods.
      RESULTS: Seventy-five LGBT trainees completed surveys and a subset of 23 survey
      respondents also participated in three focus groups. Among survey participants,
      100% identified along the queer spectrum; 10.7% identified along the trans
      spectrum; 36.0% identified as a racial or ethnic minority; and 61.3% were in
      MD/DO-granting programs. Eighty-eight percent of trainees reported working with
      at least one mentor and 48.5% of trainees had at least one mentor of the same
      sexual orientation. Seventy-two percent of trainees endorsed the importance of
      having an LGBT-identified mentor for personal development. Qualitative data
      showed that trainees valued such a mentor for positive role modeling and shared
      understanding of experiences. Fifty-nine percent of trainees felt it was
      important to have an LGBT-identified mentor for career development. LGBT peer
      networking and LGBT-related professional advice were cited as unique benefits in
      the qualitative findings. CONCLUSION: LGBT health professional trainees have
      unique personal and career development needs that may benefit from LGBT
      mentorship. Academic health centers that facilitate LGBT mentorship could enhance
      LGBT health trainees' academic productivity and personal development.

PMID- 29641313
TI  - Targeted Victimization and Suicidality Among Trans People: A Web-Based Survey.
AB  - PURPOSE: The aim of this study was to investigate the associations between a
      series of empirically known risk and protective factors and suicidality among
      trans people in Sweden. METHODS: Participants were self-selected anonymously to a
      web-based survey conducted in 2014. Univariable and multivariable logistic
      regression analyses were performed to assess associations between contributing
      factors and suicide ideation in the past 12 months and lifetime suicide attempts.
      RESULTS: The analysis included 796 trans individuals, between 15 and 94 years of
      age, who live in Sweden. A total of 37% of respondents reported that they have
      seriously considered suicide during the past 12 months and 32% had ever attempted
      a suicide. Offensive treatment during the past three months and lifetime exposure
      to trans-related violence were significantly associated with suicidality. Less
      satisfaction with contacts with friends and acquaintances and with one's own
      psychological wellbeing were associated with suicide ideation in the past 12
      months. Lack of practical support was associated with lifetime suicide attempts.
      CONCLUSIONS: Our findings show that suicidality is directly correlated with trans
      related victimization. Preventing targeted victimization is, therefore, a key
      preventive intervention against this elevated suicidality.

PMID- 29641314
TI  - Healthcare Experiences Among Young Adults Who Identify as Genderqueer or
      Nonbinary.
AB  - PURPOSE: Research on healthcare among gender-diverse populations has largely
      focused on people who describe their gender in binary terms, either as trans men
      or trans women. This qualitative study examined the healthcare experiences of
      young adults who identify as genderqueer or nonbinary (GQ/NB). METHODS:
      Participants (N = 10) were interviewed about experiences seeking and accessing
      healthcare. All were young adults (ages 23-33) in the San Francisco Bay area who
      had accessed healthcare at least once in the prior 6 months. A semistructured
      interview guide elicited conversations about gender identity and experiences of
      healthcare. Interview transcripts were analyzed using emergent coding analysis to
      identify themes. RESULTS: Participants faced unique challenges even at clinics
      specializing in gender-affirming healthcare. They felt misunderstood by providers
      who approached them from a binary transgender perspective and consequently often
      did not receive care sensitive to nonbinary identities. In response to this
      perceived bias, participants sometimes "borrowed" a binary transgender label to
      receive care, modified the healthcare they were prescribed, or went without
      healthcare. The GQ/NB young adults in our study regularly felt disrespected and
      frustrated as they sought and accessed healthcare. Participants felt that the
      binary transgender narrative pressured them to conform to binary medical
      narratives throughout healthcare interactions. CONCLUSIONS: GQ/NB young adults
      have unique healthcare needs but often do not feel understood by their providers.
      There is a need for existing healthcare systems to serve GQ/NB young adults more
      effectively.

PMID- 29641316
TI  - Characteristics and Correlates of Tobacco Use in a Community Sample of Sexual
      Minority Men and Women: Implications for Smoking Cessation Program Development.
AB  - PURPOSE: Tobacco use is the single most preventable cause of disease, death, and
      disability in the United States. Research suggests that sexual minorities have an
      increased risk for smoking and tobacco use. This study aimed to identify
      characteristics of patients affected by tobacco use disparities and examined
      demographic and substance use differences between tobacco users and nonusers in a
      sample of sexual minorities. METHODS: Patients at an urban community health
      center (specializing in the needs of sexual and gender minorities) were invited
      to complete a cross-sectional 25-item questionnaire. RESULTS: Of the 3068
      questionnaire respondents, 1543 identified as gay, lesbian, or bisexual. Of these
      sexual minority respondents, most identified as White (84.4%), 67.3% identified
      as male and 32.7% as female, with a mean age of 37.7 (SD = 9.44). More than a
      quarter of sexual minority men (26.7%) and women (28.3%) reported current tobacco
      use. Among men, younger age (OR = 0.97, CI: 0.95-0.98, P < 0.001), less education
      (OR = 0.58, CI: 0.35-0.96, P < 0.01), heroin use (OR = 3.3, CI: 1.18-9.39, P <
      0.05), and alcohol use (OR = 3.0, CI: 1.86-4.80, P < 0.001) were associated with
      increased odds of current tobacco use. Among women, younger age (OR = 0.97, CI:
      0.95-0.99, P = 0.004), less education (OR = 0.45, CI: 0.22-0.91, P < 0.001), and
      alcohol use (OR = 3.78, CI: 1.87-7.65, P < 0.001) were associated with current
      tobacco use. CONCLUSION: Cessation programs placed within the context of co
      occurring substance and alcohol use for young sexual minority tobacco users from
      lower socioeconomic backgrounds may be particularly effective.

PMID- 29641315
TI  - Quality Primary Care and Family Planning Services for LGBT Clients: A
      Comprehensive Review of Clinical Guidelines.
AB  - LGBT clients have unique healthcare needs but experience a wide range of quality
      in the care that they receive. This study provides a summary of clinical
      guideline recommendations related to the provision of primary care and family
      planning services for LGBT clients. In addition, we identify gaps in current
      guidelines, and inform future recommendations and guidance for clinical practice
      and research. PubMed, Cochrane, and Agency for Healthcare Research and Quality
      electronic bibliographic databases, and relevant professional organizations'
      websites, were searched to identify clinical guidelines related to the provision
      of primary care and family planning services for LGBT clients. Information
      obtained from a technical expert panel was used to inform the review. Clinical
      guidelines meeting the inclusion criteria were assessed to determine their
      alignment with Institute of Medicine (IOM) standards for the development of
      clinical practice guidelines and content relevant to the identified themes. The
      search parameters identified 2,006 clinical practice guidelines. Seventeen
      clinical guidelines met the inclusion criteria. Two of the guidelines met all
      eight IOM criteria. However, many recommendations were consistent regarding
      provision of services to LGBT clients within the following themes: clinic
      environment, provider cultural sensitivity and awareness, communication,
      confidentiality, coordination of care, general clinical principles, mental health
      considerations, and reproductive health. Guidelines for the primary and family
      planning care of LGBT clients are evolving. The themes identified in this review
      may guide professional organizations during guideline development, clinicians
      when providing care, and researchers conducting LGBT-related studies.

PMID- 29641317
TI  - Culturally Competent Care for Sexual and Gender Minority Patients at National
      Cancer Institute-Designated Comprehensive Cancer Centers.
AB  - PURPOSE: This study sought to identify the policies and guidelines regarding
      culturally competent care of sexual and gender minority (SGM) cancer patients and
      survivors at National Cancer Institute (NCI)-Designated Comprehensive Cancer
      Centers. METHODS: This study used an in-depth interview qualitative approach.
      Semistructured interviews were conducted via telephone with representatives from
      21 of the 45 NCI-Designated Comprehensive Cancer Centers in 2015. Verbatim
      transcripts were created from the audiotapes for content analysis. RESULTS: Two
      main themes were identified as follows: (1) patient-focused experiences and
      support and (2) organization-focused development activities. Most of the cancer
      centers in this study had an advisory committee to assist with SGM policies and
      guidelines. Despite the existence of these committees, the majority of centers
      did not have explicit policies, guidelines, or routine practices addressing the
      following issues: the collection and integration of sexual orientation and gender
      identity information in the medical record, gender-neutral language on patient
      forms, patient educational materials with SGM-specific health concerns, SGM
      specific support for cancer survivors, or required SGM-specific cultural
      competency trainings for medical and nonmedical staff. CONCLUSION: In general,
      the cancer centers in this study lacked institutional policies, guidelines, and
      practices focused on patient-centered cancer care for SGM populations.
      Coordinated efforts are needed to systemically improve patient-centered cancer
      care for these populations.

PMID- 29641318
TI  - Gene Therapy in Lipoprotein Lipase Deficiency: Case Report on the First Patient
      Treated with Alipogene Tiparvovec Under Daily Practice Conditions.
AB  - One-year results are reported of the first lipoprotein lipase deficiency (LPLD)
      patient treated with alipogene tiparvovec, which is indicated for the treatment
      of patients with genetically confirmed LPLD suffering from acute and recurrent
      pancreatitis attacks (PAs) despite dietary restrictions and expressing >5% of
      lipoprotein lipase (LPL) mass compared to a healthy control. During clinical
      development, alipogene tiparvovec has shown improvement of chylomicron metabolism
      and reduction of pancreatitis incidence up to 5.8 years post treatment. A 43-year
      old female presented with severe hypertriglyceridemia (median triglyceride [TG]
      value of 3,465 mg/dL) and a history of 37 PAs within the last 25 years, despite
      treatment with fibrates, omega 3 fatty acids, and-since 2012-twice-weekly lipid
      apheresis. LPLD was confirmed by identification of two different pathogenic
      variants in the LPL gene located on separate alleles and therefore constituting a
      compound heterozygous state. With a detectable LPL mass level of 55.1 ng/mL, the
      patient was eligible for alipogene tiparvovec treatment, and in September 2015,
      she receved 40 injections (1 * 1012 genome copies/kg) in the muscles of her upper
      legs under epidural anesthesia and immunosuppressive therapy. Alipogene
      tiparvovec was well tolerated: no injection site or systemic reactions were
      observed. Median TG values decreased by 52%, dropping to 997 mg/dL at month 3 and
      increasing thereafter. Within the first 18 months post treatment, the patient
      discontinued plasmapheresis and had no abdominal pain or PAs. In March 2017, the
      patient suffered from a PA due to diet violation. Within the first 12 months post
      treatment, overall quality of life improved, and no change in humoral or cellular
      immune response against LPL or AAV-1 was observed. In conclusion, alipogene
      tiparvovec was well tolerated, with a satisfactory response to treatment. Long
      term effects on the recurrence of pancreatitis continue to be monitored.

PMID- 29641319
TI  - Effective Targeting of Multiple B-Cell Maturation Antigen-Expressing
      Hematological Malignances by Anti-B-Cell Maturation Antigen Chimeric Antigen
      Receptor T Cells.
AB  - B-cell maturation antigen (BCMA) expression has been proposed as a marker for the
      identification of malignant plasma cells in patients with multiple myeloma (MM).
      Nearly all MM tumor cells express BCMA, while normal tissue expression is
      restricted to plasma cells and a subset of mature B cells. Consistent BCMA
      expression was confirmed on MM biopsies (29/29 BCMA+), and it was further
      demonstrated that BCMA is expressed in a substantial number of lymphoma samples,
      as well as primary chronic lymphocytic leukemia B cells. To target BCMA using
      redirected autologous T cells, lentiviral vectors (LVV) encoding chimeric antigen
      receptors (CARs) were constructed with four unique anti-BCMA single-chain
      variable fragments, fused to the CD137 (4-1BB) co-stimulatory and CD3zeta
      signaling domains. One LVV, BB2121, was studied in detail, and BB2121 CAR
      transduced T cells (bb2121) exhibited a high frequency of CAR + T cells and
      robust in vitro activity against MM cell lines, lymphoma cell lines, and primary
      chronic lymphocytic leukemia peripheral blood. Based on receptor quantification,
      bb2121 recognized tumor cells expressing as little as 222 BCMA molecules per
      cell. The in vivo pharmacology of anti-BCMA CAR T cells was studied in NSG mouse
      models of human MM, Burkitt lymphoma, and mantle cell lymphoma, where mice
      received a single intravenous administration of vehicle, control vector
      transduced T cells, or anti-BCMA CAR-transduced T cells. In all models, the
      vehicle and control CAR T cells failed to inhibit tumor growth. In contrast,
      treatment with bb2121 resulted in rapid and sustained elimination of the tumors
      and 100% survival in all treatment models. Together, these data support the
      further development of anti-BCMA CAR T cells as a potential treatment for not
      only MM but also some lymphomas.

PMID- 29641320
TI  - High-Throughput Screening Identifies Kinase Inhibitors That Increase Dual Adeno
      Associated Viral Vector Transduction In Vitro and in Mouse Retina.
AB  - Retinal gene therapy based on adeno-associated viral (AAV) vectors is safe and
      efficient in humans. The low intrinsic DNA transfer capacity of AAV has been
      expanded by dual vectors where a large expression cassette is split in two halves
      independently packaged in two AAV vectors. Dual AAV transduction efficiency,
      however, is greatly reduced compared to that obtained with a single vector. As
      AAV intracellular trafficking and processing are negatively affected by
      phosphorylation, this study set to identify kinase inhibitors that can increase
      dual AAV vector transduction. By high-throughput screening of a kinase inhibitors
      library, three compounds were identified that increase AAV transduction in vitro,
      one of which has a higher effect on dual than on single AAV vectors. Importantly,
      the transduction enhancement is exerted on various AAV serotypes and is not
      transgene dependent. As kinase inhibitors are promiscuous, siRNA-mediated
      silencing of targeted kinases was performed, and AURKA and B, PLK1, and PTK2 were
      among those involved in the increase of AAV transduction levels. The study shows
      that kinase inhibitor administration reduces AAV serotype 2 (AAV2) capsid
      phosphorylation and increases the activity of DNA-repair pathways involved in AAV
      DNA processing. Importantly, the kinase inhibitor PF-00562271 improves dual AAV8
      transduction in photoreceptors following sub-retinal delivery in mice. The study
      identifies kinase inhibitors that increase dual and single AAV transduction by
      modulating AAV entry and post-entry steps.

PMID- 29641322
TI  - Preclinical Efficacy and Safety of CD19CAR Cytokine-Induced Killer Cells
      Transfected with Sleeping Beauty Transposon for the Treatment of Acute
      Lymphoblastic Leukemia.
AB  - Infusion of patient-derived CD19-specific chimeric antigen receptor (CAR) T cells
      engineered by viral vectors achieved complete remission and durable response in
      relapsed and refractory (r/r) B-lineage neoplasms. Here, we expand on those
      findings by providing a preclinical evaluation of allogeneic non-viral cytokine
      induced killer (CIK) cells transfected with the Sleeping Beauty (SB) transposon
      CD19CAR (CARCIK-CD19). Specifically, thanks to a large-scale 18-day manufacturing
      process, it was possible to achieve stable CD19CAR expression (62.425 +/- 6.399%)
      and efficient T-cell expansion (23.36 +/- 3.00-fold). Frozen/thawed CARCIK-CD19
      remained fully functional both in vitro and in an established patient-derived
      xenograft (PDX) of MLL-ENL rearranged acute lymphoblastic leukemia (ALL). CARCIK
      CD19 showed a dose-dependent antitumor response and prolonged persistence in a
      PDX, bearing the feature of a Philadelphia-like ALL with PAX5/AUTS2
      translocation, and in a survival model of lymphoma, achieving complete
      eradication of disseminated tumors. Finally, the infusion of CARCIK-CD19 proved
      to be safe and well tolerated in a biodistribution and toxicity model. The
      infused cells persisted in the hematopoietic and post-injection perfused organs
      until the end of the study and consisted of CD8+, CD56+, and CAR+ T cells.
      Overall, these findings provide important implications for non-viral technology
      and the proof-of-concept that donor-derived CARCIK-CD19 are indeed effective
      against relapsed ALL, a possibility that will be tested in Phase I/II clinical
      trials after allogeneic hematopoietic stem-cell transplantation.

PMID- 29641321
TI  - A Calsequestrin Cis-Regulatory Motif Coupled to a Cardiac Troponin T Promoter
      Improves Cardiac Adeno-Associated Virus Serotype 9 Transduction Specificity.
AB  - Adeno-associated virus serotype 9 (AAV9) is an efficient vector for gene transfer
      to the myocardium. However, the use of ubiquitous promoters, such as the
      cytomegalovirus (CMV) promoter, can result in expression of the transgene in
      organs other than the heart. This study tested if the efficiency and specificity
      of cardiac transcription from a chicken cardiac troponin T (TnT) promoter could
      be further increased by incorporating a cardiomyocyte-specific transcriptional
      cis-regulatory motif from human calsequestrin 2 (CS-CRM4) into the expression
      cassette (Enh.TnT). The efficiency of luciferase expression from the TnT and
      Enh.TnT constructs was compared to expression of luciferase under the control of
      the CMV promoter in both adult and neonatal mice. Overall, expression levels of
      luciferase in the heart were similar in mice injected with AAV9.TnT.Luc,
      AAV9.Enh.TnT.Luc and AAV9.CMV.Luc. In contrast, expression levels of luciferase
      activity in nontarget organs, including the liver and muscle, was lower in mice
      injected with the AAV9.TnT.Luc compared to AAV9.CMV.Luc and was negligible with
      AAV9.Enh.TnT. In neonates, in organs other than the heart, luciferase expression
      levels were too low to be quantified for all constructs. Taken together, the data
      show that the AAV9 Enh.TnT constructs drives high levels of expression of the
      transgene in the myocardium, with insignificant expression in other organs. These
      properties reduce the risks associated with the AAV9-mediated expression of the
      therapeutic protein of interest in nontarget organs. The excellent cardiac
      specificity should allow for the use of higher vector doses than are currently
      used, which might be essential to achieve the levels of transgene expression
      necessary for therapeutic benefits. Taken together, the findings suggest that the
      Enh.TnT transcription unit is a potentially attractive tool for clinical cardiac
      gene therapy in adults.

PMID- 29641323
TI  - Amelioration of Alpha-1 Antitrypsin Deficiency Diseases with Genome Editing in
      Transgenic Mice.
AB  - Alpha-1 antitrypsin deficiency (AATD) is a hereditary liver disease caused by
      mutations in the SERPINA1 serine protease inhibitor gene. Most severe patients
      are homozygous for PiZ alleles (PiZZ; amino acid E324K), which lead to protein
      aggregates in hepatocytes and reduced circulating levels of AAT. The liver
      aggregates typically lead to fibrosis, cirrhosis, and hepatocellular carcinoma,
      and the reduced circulating AAT levels can lead to emphysema and chronic
      obstructive pulmonary diseases. In this study, two CRISPR/Cas9 gene editing
      approaches were used to decrease liver aggregates and increase systemic AAT-M
      levels in the PiZ transgenic mouse. In the first approach, AAT expression in
      hepatocytes was reduced more than 98% following the systemic delivery of AAV8
      CRISPR targeting exon 2 of hSERPINA1, leading to reduced aggregates in
      hepatocytes. In the second approach, a second adeno-associated virus, which
      provided the donor template to correct the Z mutation, was also administered.
      These treated mice had reduced AAT expression (> 98%) and a low level (5%) of
      wildtype AAT-M mRNA. Taken together, this study shows that CRISPR gene editing
      can efficiently reduce liver expression of AAT-Z and restore modest levels of
      wildtype AAT-M in a mouse model of AATD, raising the possibility of CRISPR gene
      editing therapeutic for AATD.

PMID- 29641324
TI  - Gene Therapy with Tetracycline-Regulated Human Recombinant COLIA1 cDNA Direct
      Adenoviral Delivery Enhances Fracture Healing in Osteoporotic Rats.
AB  - A number of previous studies have indicated that the genetic variation at the
      collage type I alpha 1 (COLIA1) gene locus influences susceptibility to
      osteoporosis. However, seldom have studies reported the effect of gene delivery
      using an adenovirus vector carrying human recombinant COLIA1 cDNA on stimulating
      osteogenic activity of osteoblasts and enhancing fracture healing of
      ovariectomized rats. The current study was performed to demonstrate whether
      direct gene delivery using an adenovirus vector carrying human recombinant COLIA1
      cDNA could stimulate osteogenic activity of osteoblast in vitro and enhance
      fracture healing of ovariectomized rats in vivo. In vitro, the tet-on system
      regulated COLIA1 gene adenovirus was constructed and transfected to osteoblasts.
      COLIA1 mRNA and collagen type I levels were assessed by reverse transcription
      polymerase chain reaction and enzyme-linked immunosorbent assay to determine
      whether adenovirus transfected successfully. Osteogenic activity of the
      osteoblasts was assessed by alkaline phosphatase activity, immunohistochemical
      staining, immunofluorescent staining, mineralized matrix formation, and
      extracellular calcium levels. In vivo, adenovirus-delivered COLIA1 gene was
      injected into the fracture site of the tibia in an ovariectomized rat model of
      osteoporosis, and bone callus condition was assessed to determine whether the
      COLIA1 gene could accelerate osteoporotic fracture healing. In vitro, the results
      showed that COLIA1 gene adenovirus transfection could increase osteoblast COLIA1
      gene expression and collagen type I protein synthesis, increase alkaline
      phosphatase activity, and stimulate calcium nodules formation, which exhibited a
      direct osteogenic effect on the osteoblasts. In vivo, local injection of COLIA1
      gene adenovirus increased collagen type I expression, restored bone mineral
      density, and accelerated fracture healing in ovariectomized rats, without
      increasing serum collagen type I and liver COLIA1 mRNA levels. This study
      suggests direct gene delivery using an adenovirus carrying human COLIA1 cDNA can
      stimulate the osteogenic activity of osteoblasts in vitro and enhance bone
      fracture healing in vivo. The tet-on system is an ideal gene regulatory system
      for effective and safe regulation of the therapeutic gene.

PMID- 29641326
TI  - Perioperative mortality rate and risk factors for death in dogs undergoing
      surgery for treatment of thoracic trauma: 157 cases (1990-2014).
AB  - OBJECTIVE To determine perioperative mortality rate and identify risk factors
      associated with outcome in dogs with thoracic trauma that underwent surgical
      procedures and to evaluate the utility of the animal trauma triage (ATT) score in
      predicting outcome. DESIGN Retrospective case series. ANIMALS 157 client-owned
      dogs. PROCEDURES Medical records databases of 7 veterinary teaching hospitals
      were reviewed. Dogs were included if trauma to the thorax was documented and the
      patient underwent a surgical procedure. History, signalment, results of physical
      examination and preoperative laboratory tests, surgical procedure, perioperative
      complications, duration of hospital stay, and details of follow-up were recorded.
      Descriptive statistics and ATT scores were calculated, and logistic regression
      analysis was performed. RESULTS 123 of 157 (78%) patients underwent thoracic
      surgery, and 134 of 157 (85.4%) survived to discharge. Mean +/- SD ATT score for
      nonsurvivors was 8 +/- 2.4. In the multivariable model, female dogs and dogs that
      did not experience cardiac arrest as a postoperative complication had odds of
      survival 6 times and 102 times, respectively, those of male dogs and dogs that
      did experience cardiac arrest as a postoperative complication. Additionally,
      patients with a mean ATT score < 7 had odds of survival 5 times those of patients
      with an ATT score >= 7. CONCLUSIONS AND CLINICAL RELEVANCE The overall
      perioperative mortality rate was low for patients with thoracic trauma undergoing
      surgery in this study. However, male dogs and dogs that experienced cardiac
      arrest had a lower likelihood of survival to discharge. The ATT score may be a
      useful adjunct to assist clinical decision-making in veterinary patients with
      thoracic trauma.

PMID- 29641327
TI  - In This Issue * May 1, 2018.

PMID- 29641325
TI  - Host genetics contributes to the effectiveness of dendritic cell-based HIV
      immunotherapy.
AB  - Systems biological analysis has recently revealed how innate immune variants as
      well as gut microbiota impact the individual response to immunization. HIV
      infected (HIV+) patients have a worse response rate after standard vaccinations,
      possibly due to the immune exhaustion, increased gut permeability and microbial
      translocation. In the last decade, dendritic cells (DC)-based immunotherapy has
      been proposed as an alternative approach to control HIV plasma viral load,
      however clinical trials showed a heterogeneity of immunization response.
      Hypothesizing that host genetics may importantly affects the outcome of
      immunotherapy in HIV+ patients, genetic polymorphisms' distribution and gene
      expression modulation were analyzed in a phase I/II clinical trial of DC-based
      immunotherapy according to immunization response, and quality of vaccine product
      (DC). Polymorphisms in genes previously associated with progression of HIV
      infection to AIDS (i.e.: PARD3B, CCL5) contribute to a better response to
      immunotherapy in HIV+ individuals, possibly through a systemic effect on host
      immune system, but also directly on vaccine product. Genes expression profile
      after immunization correlates with different degrees of immune chronic
      activation/exhaustion of HIV+ patients (i.e. PD1, IL7RA, EOMES), but also with
      anti-viral response and DC quality (i.e.: APOBEC3G, IL8, PPIA), suggested that an
      immunocompetent individual would have a better vaccine response. These findings
      showed once more that host genetics can affect the response to DC-based
      immunotherapy in HIV+ individuals, contributing to the heterogeneity of response
      observed in concluded trials; and it can be used as predictor of immunization
      success.

PMID- 29641329
TI  - Building strong and sustainable partnerships to protect, promote, and advance
      your interests.

PMID- 29641328
TI  - Emotional responses of clients to veterinarian communication style during a
      vaccination visit in companion animal practice.
AB  - OBJECTIVE To study the effects of veterinarian communication (ie, the information
      provided and gaze and body direction) and vaccination style on the emotions and
      physiologic reactions experienced by clients and on clients' evaluation of the
      expertise and trustworthiness of the veterinarian. DESIGN Simulation study.
      PARTICIPANTS 20 small animal clients. PROCEDURES Participants were shown 12
      videos of a female veterinarian in which she first provided information about
      puppy vaccination and then performed the procedure. The veterinarian's behavior
      varied regarding the information provided about the vaccination (ie, scarce,
      factual, or emotional), her gaze and body direction (ie, direct or 30 degrees 
      averted), and her vaccination style (ie, routine or emotional). While the
      participants watched the videos, their corrugator supercilii muscle activity
      (corrugator supercilii muscles are activated when frowning) and skin conductance
      activity were measured. Participants also rated the emotions they experienced
      (ie, valence and arousal) and assessed the veterinarian's behavior (ie, expertise
      and trustworthiness). RESULTS Overall, emotional information, a direct gaze and
      body direction, and an emotional vaccination style were associated with more
      pleasant emotions and higher ratings of the expertise and trustworthiness of the
      veterinarian's behavior by clients. CONCLUSIONS AND CLINICAL RELEVANCE Results
      suggested that through certain behavioral actions, veterinarians may positively
      affect the emotions and feelings experienced by clients during veterinary clinic
      visits, even in the case of vaccination visits, which can be considered routine
      visits from the viewpoint of the veterinarian.

PMID- 29641330
TI  - Survey of veterinary specialists regarding their knowledge of radiation safety
      and the availability of radiation safety training.
AB  - OBJECTIVE To evaluate the knowledge of various veterinary specialists regarding
      various radiation safety matters and determine the availability of radiation
      safety training. DESIGN Cross-sectional study. SAMPLE 164 radiology, 81 internal
      medicine, and 108 emergency and critical care (ECC) specialists. PROCEDURES An
      online survey was developed regarding knowledge of and training in radiation
      safety, and invitations were sent via email through the email lists of the
      veterinary internal medicine, ECC, and radiology specialty colleges. Responses
      were summarized, and comparisons were made between radiologists and internal
      medicine and ECC clinicians. RESULTS 65.5% (38 /58) of respondents from academic
      institutions and 30.0% (33/110) of respondents from private practices indicated
      that radiation safety training was mandatory at their institution for personnel
      who work with ionizing radiation-emitting equipment, and 80.2% (85/106) and 56.6%
      (77/136), respectively, had received some radiation safety training. Low
      proportions of radiologists and internal medicine and ECC clinicians correctly
      identified the effective dose of ionizing radiation associated with 3-phase
      esophagography and 3-phase abdominal CT. Many radiologists (92/153 [60.1%]) and
      nonradiologists (92/179 [51.4%]) believed that the effective doses used in
      veterinary practice pose no increased risk of fatal cancer to their patients.
      CONCLUSIONS AND CLINICAL RELEVANCE Radiation safety training, although more
      common in academia, was not universally available and may not meet radiography
      equipment license requirements for some institutions. Most radiologists, internal
      medicine clinicians, and ECC clinicians had a poor understanding of the amount of
      ionizing radiation associated with medical imaging procedures and the potential
      hazards to their patients.

PMID- 29641331
TI  - Pathology in Practice.

PMID- 29641332
TI  - Factors associated with postoperative complications in healthy horses after
      general anesthesia for ophthalmic versus non-ophthalmic procedures: 556 cases
      (2012-2014).
AB  - OBJECTIVE To compare complications between healthy horses undergoing general
      anesthesia for ophthalmic versus non-ophthalmic procedures and identify potential
      risk factors for the development of complications. DESIGN Retrospective case
      series. ANIMALS 502 horses (556 anesthetic procedures). PROCEDURES Medical
      records from January 2012 through December 2014 were reviewed to identify horses
      undergoing general anesthesia. Signalment, body weight, drugs administered,
      patient positioning, procedure type (ophthalmic, orthopedic, soft tissue, or
      diagnostic imaging), specific procedure, procedure time, anesthesia time,
      recovery time, recovery quality, and postoperative complications were recorded.
      RESULTS Patients underwent general anesthesia for ophthalmic (n = 106),
      orthopedic (246), soft tissue (84), diagnostic imaging (110), or combined (10)
      procedures. Mean procedure, anesthesia, and recovery times were significantly
      longer for patients undergoing ophthalmic versus non-ophthalmic procedures.
      Excluding diagnostic imaging procedures, there was a significant positive
      correlation between surgery time and recovery time. Within ophthalmic procedures,
      surgery time, anesthesia time, and recovery time were significantly greater for
      penetrating keratoplasty versus other ophthalmic procedures. There was a
      significantly higher rate of postoperative colic following penetrating
      keratoplasty, compared with all other ophthalmic procedures. CONCLUSIONS AND
      CLINICAL RELEVANCE Results suggested that in healthy horses, duration of general
      anesthesia should be minimized to decrease the risk of postanesthetic
      complications. Judicious use of orally administered fluconazole is recommended
      for horses undergoing general anesthesia. For horses undergoing a retrobulbar
      nerve block during general anesthesia, use of the lowest effective volume is
      suggested.

PMID- 29641334
TI  - What Is Your Diagnosis?

PMID- 29641335
TI  - Effects of therapeutic plasma exchange on serum immunoglobulin concentrations in
      a dog with refractory immune-mediated hemolytic anemia.
AB  - CASE DESCRIPTION A 9-year-old 8.3-kg (18.3-lb) neutered male Miniature Schnauzer
      was referred for diagnosis and treatment of a sudden onset of lethargy, anorexia,
      vomiting, and pallor. CLINICAL FINDINGS On physical examination, the dog was
      lethargic with pale mucous membranes and a capillary refill time >= 2 seconds.
      Skin and sclera were mildly icteric. Signs of pain were elicited during abdominal
      palpation, and an enlarged spleen was noted. Results of agglutination testing and
      cytologic findings were consistent with immune-mediated hemolytic anemia (IMHA).
      No contributing factors for development of IMHA were identified. TREATMENT AND
      OUTCOME Initial treatment included management with immunosuppressant medications.
      Three packed RBC transfusions were administered, but clinical signs continued to
      progress. Therefore, therapeutic plasma exchange (TPE) was performed 5 and 9 days
      after admission. Following each TPE procedure, the dog had an appreciable
      clinical improvement and decrease in RBC autoagglutination, and the Hct
      stabilized. Serum IgG and IgM concentrations were measured during and after both
      TPE procedures. Despite anticoagulative treatment, the dog developed a thrombus
      in the splenic vein, necessitating a splenectomy. CLINICAL RELEVANCE The decrease
      and rebound in serum IgG and IgM concentrations following TPE provided evidence
      that TPE may have the same immunomodulatory effects in dogs as have been proposed
      to occur in people. Further, findings suggested that TPE may be a useful
      alternative in dogs with refractory IMHA when traditional treatments fail.

PMID- 29641336
TI  - Ultrasonographic evaluation of the canine urinary bladder following cystotomy for
      treatment of urolithiasis.
AB  - OBJECTIVE To describe the ultrasonographic appearance of the urinary bladder
      incision site in dogs that underwent cystotomy for treatment of urolithiasis.
      DESIGN Prospective, longitudinal study. ANIMALS 18 client-owned dogs. PROCEDURES
      Dogs underwent urinary bladder ultrasonography at baseline (<= 1 day before
      surgery) and at 1 day and approximately 2, 6, and 12 weeks after cystotomy for
      urocystolith removal. A baseline ratio between ventral (cystotomy site) and
      corresponding dorsal midline wall thickness was calculated and used to account
      for measurement variations attributable to bladder distension at subsequent
      visits. Patient signalment, weight, medications administered, urocystolith
      composition, and culture results were recorded. Clinical signs, reoccurrence of
      hyperechoic foci, and suture visualization were recorded at follow-up
      examinations. Variables were evaluated for association with cystotomy site
      thickening and resolution of thickening. RESULTS Median wall thickness at the
      ventral aspect of the bladder was significantly greater than that of the
      corresponding dorsal aspect at baseline. Cystotomy site thickening peaked 1 day
      after surgery and decreased at subsequent visits in a linear manner. Twelve weeks
      after surgery, 5 of 10 clinically normal dogs evaluated had persistent cystotomy
      site thickening. Eleven of 18 dogs had reoccurrence of hyperechoic foci within
      the bladder at some time during the study (median time to first detection, 17
      days after surgery). CONCLUSIONS AND CLINICAL RELEVANCE Persistent cystotomy site
      thickening can be present up to 3 months after cystotomy for urolithiasis in dogs
      without lower urinary tract signs. Reoccurrence of hyperechoic foci in the
      bladder, although subclinical, was detected earlier and at a higher rate than
      anticipated.

PMID- 29641337
TI  - Development and psychometric testing of the Canine Owner-Reported Quality of Life
      questionnaire, an instrument designed to measure quality of life in dogs with
      cancer.
AB  - OBJECTIVE To describe development and initial psychometric testing of an owner
      reported questionnaire designed to standardize measurement of general quality of
      life (QOL) in dogs with cancer. DESIGN Key-informant interviews, questionnaire
      development, and field trial. SAMPLE Owners of 25 dogs with cancer for item
      development and pretesting and owners of 90 dogs with cancer for reliability and
      validity testing. PROCEDURES Standard methods for development and testing of
      questionnaire instruments intended to measure subjective states were used. Items
      were generated, selected, scaled, and pretested for content, meaning, and
      readability. Response items were evaluated with exploratory factor analysis and
      by assessing internal consistency (Cronbach alpha) and convergence with global
      QOL as determined with a visual analog scale. Preliminary tests of stability and
      responsiveness were performed. RESULTS The final questionnaire-which was named
      the Canine Owner-Reported Quality of Life (CORQ) questionnaire-contained 17 items
      related to observable behaviors commonly used by owners to evaluate QOL in their
      dogs. Several items pertaining to physical symptoms performed poorly and were
      omitted. The 17 items were assigned to 4 factors-vitality, companionship, pain,
      and mobility-on the basis of the items they contained. The CORQ questionnaire and
      its factors had high internal consistency (Cronbach alpha = 0.68 to 0.90) and
      moderate to strong correlations (r = 0.49 to 0.71) with global QOL as measured on
      a visual analog scale. Preliminary testing indicated good test-retest reliability
      and responsiveness to improvements in overall QOL. CONCLUSIONS AND CLINICAL
      RELEVANCE The CORQ questionnaire was a valid, reliable owner-reported
      questionnaire that measured general QOL in dogs with cancer and showed promise as
      a clinical trial outcome measure for quantifying changes in individual dog QOL
      occurring in response to cancer treatment and progression.

PMID- 29641339
TI  - Pathology in Practice.

PMID- 29641338
TI  - Effects of milbemycin oxime, combined with spinosad, when administered orally to
      microfilaremic dogs infected with adult heartworms (Dirofilaria immitis).
AB  - OBJECTIVE To evaluate the safety of PO administration of a milbemycin oxime (MBO)
      and spinosad product to heartworm (Dirofilaria immitis)-positive microfilaremic
      dogs. DESIGN Randomized, blinded, complete block trial. ANIMALS 32 purebred
      Beagles with a patent heartworm infection. PROCEDURES Dogs ranked by sex and
      microfilaria counts (range, 398 to 1,980 microfilaria/mL) were assigned to 4
      groups of 8 to receive 3 treatments PO at 28-day intervals beginning on day 0:
      placebo (control group) or spinosad-MBO tablets containing MBO at the upper end
      of the label dose range (0.75 to 1 mg/kg [0.34 to 0.45 mg/lb]; 1* group) or 3 (3*
      group) or 5 (5* group) times that dose. Blood samples were collected at various
      points for adult heartworm antigen and Knott tests. Necropsies were performed on
      day 65, and recovered adult heartworms were counted. RESULTS 1 control dog died
      from heartworm-associated complications. Other adverse events included mild,
      transient emesis (1 dog in each of the 1* and 5* groups and 3 dogs in the 3*
      group). Similar adult heartworm counts (range, 13 to 41) were obtained for all 4
      groups. Results of blood antigen and microfilaria tests were positive throughout
      the study, with 1 exception in each of the 3* and 5* groups. Mean microfilaria
      counts increased with time in the control group, whereas reductions from baseline
      in treated groups ranged from 61.5% to 96.4%. CONCLUSIONS AND CLINICAL RELEVANCE
      The evaluated MBO-spinosad formulation caused no severe adverse events when
      administered PO to microfilaremic dogs. Although microfilaria counts decreased
      following treatment, repeated monthly MBO treatments were incompletely
      microfilaricidal, suggesting MBO should not be used as a microfilaricide.

PMID- 29641340
TI  - Ulcer-free, hospital-free and activity-rich days: three key metrics for the
      diabetic foot in remission.

PMID- 29641341
TI  - Traditional culture methods fail to detect principle pathogens in necrotising
      soft tissue infection: a case report.
AB  - OBJECTIVE: Necrotising soft tissue infections (NSTIs) progress rapidly and
      mortality remains high, ranging from 10% to 30%, representing a significant
      challenge for health professionals. Early accurate diagnosis is crucial because
      timely and aggressive surgical intervention remains the number one indicator for
      a better clinical outcome. Understanding the microbial background of NSTIs would
      aid early diagnosis. PRESENTATION: We present a case of NSTI, in a seemingly
      healthy adult male, originating from a tooth abscess. The NSTI progressed
      rapidly, and eventually covered the patient's chest and abdominal skin and
      underlying soft tissue. RESULTS: Traditional blood and tissue culture only found
      Group C Streptococcus where 16S sequencing detected abundant Prevotella spp., a
      more likely causal organisms of the NSTI. The use of antibiotics with the
      approriate anaerobe coverage, in combination with timely surgical intervention,
      contributed to the ultimate successful clinical outcome. Complete wound healing
      and successful graft was achieved within one month of diagnosis of the microbes
      present. CONCLUSION: While surgical intervention remains the most important
      consideration in treatment of NSTI, correct identifcation of the microbial flora
      could also contribute to successful treatment.

PMID- 29641342
TI  - Economic and clinical comparison of 2-octyl cyanoacrylate/polymer mesh tape with
      skin staples in total knee replacement.
AB  - OBJECTIVE: To compare economic and clinical outcomes between skin staples and 2
      octyl cyanoacrylate plus polymer mesh tape, Dermabond Prineo skin closure system,
      (SCS) among patients undergoing total knee replacement (TKR). METHOD:
      Retrospective, observational study using the Premier Healthcare Database, which
      comprises hospital administrative and billing data for over 700 hospitals in the
      US. Patients selected for study had an elective hospital admission, with
      discharge occurring between January 2012 and September 2015, carrying primary ICD
      9-CM procedure and diagnosis codes for TKR and osteoarthritis. Patients were
      classified into two mutually-exclusive groups based on billing records during the
      index admission: those with billing record(s) for the skin closure system (SCS
      group); and those with billing record(s) for skin staples (staple group). Primary
      outcomes were index admission's length of stay (LOS), total hospital costs, and
      discharge status (skilled nursing facility (SNF)/other versus home/home health
      care); exploratory outcomes included operating room time (ORT) during index
      admission and 30, 60, and 90-day readmissions. The SCS and staple groups were
      propensity score matched (1:1/nearest neighbour/caliper=0.10) on patient,
      hospital, and provider characteristics. Multivariable regressions accounting for
      hospital-level clustering after matching were used to compare outcomes between
      study groups. RESULTS: Each group comprised 971 patients (1942 total patients;
      mean age: 65.3 years; female: 63.5%). The groups were generally well-balanced on
      matching covariates: mean standardised difference calculated across 49
      covariates=0.049. Compared with the staple group, the SCS group had statistically
      significant shorter LOS (2.8 days versus 3.2 days, p=0.002), lower rate of
      discharge to SNF/other versus home/home health-care (26.4% versus 38.5%,
      p=0.011), and lower rate of 30, 60, and 90-day readmissions (30-day, 1.8% versus
      4.4%, p=0.006; 60-day, 3.0% versus 5.4%, p<0.001; 90-day, 5.4% versus 7.4%,
      p=0.016). Differences between the groups for other outcomes were not
      statistically significant. CONCLUSION: Among patients undergoing TKR, use of the
      SCS was associated with shorter LOS, less resource intensive discharge status,
      and lower rates of all-cause readmission as compared with skin staples.

PMID- 29641343
TI  - Pressure ulcer prevalence and perceptions on prevention: a hospital-wide survey
      of health professionals.
AB  - OBJECTIVE: Hospital-acquired pressure ulcers (HAPUs) remain a problem despite
      numerous prevention initiatives. To understand why, it is necessary to know
      health professionals' perceptions regarding the importance of prevention, and the
      usability of current initiatives. We hypothesised that positive perceptions of
      existing initiatives would not be correlated with low HAPU prevalence, and that
      health professionals would perceive the initiatives to have a low usability.
      METHOD: A two-part, online survey was developed and distributed electronically to
      nurses, in-training physicians and attending physicians, across all inpatient and
      perioperative departments of an academic hospital. Part one of the survey was the
      Agency for Healthcare Research and Quality (AHRQ) Staff Attitude Scale on beliefs
      regarding PU prevention; part two was additional questions on the usability of
      existing preventative initiatives. The results of the survey were compared with
      quarterly HAPU prevalence data by hospital unit. RESULTS: In total, 839 health
      professionals completed the survey (579 nurses, 131 residents, 119 attending
      physicians). The mean score for the AHRQ survey was 42.5 (>=40 denoting positive
      perceptions). There was a moderate correlation between AHRQ scores and prevalence
      of HAPUs (r=-0.60, p=0.402). For usability, repositioning was felt to be the most
      effective intervention (mean: 4.54, standard deviation (SD): 0.64), while
      educational posters were felt to be the least effective (mean: 3.31, SD: 0.99).
      Respondents generally rated satisfaction much lower, with no single initiative
      significantly better than the others (range: 3.21-3.79). Perceived effectiveness
      and satisfaction were all positively correlated. CONCLUSION: High HAPU
      prevalence, despite position perceptions, suggests that prevention methods are
      not as effective as thought, or they are not being used as widely as they should.
      Further research should take advantage of positive attitudes by prospectively
      investigating the usability of novel interventions.

PMID- 29641344
TI  - Glycaemic indices and haemoglobin A1c as predictors for non-healing ulcers.
AB  - OBJECTIVE: Non-healing lower extremity ulcers (NHLU) are a common podiatric
      complication of diabetes, with poor glycaemic control as a risk factor for
      development. Glycaemic indices, such as haemoglobin A1c (HbA1c) and fasting
      plasma glucose (FPG), are used to diagnose and to monitor diabetes. Using a
      population-based, nationally representative sample, we evaluate the relationship
      between glycaemic indices and NHLU (as defined by the patient) to propose
      glycaemic thresholds for clinical suspicion of patient NHLU status. METHOD: Using
      data from the 1999-2004 National Health and Nutrition Examination Surveys
      (NHANES), a total of 9769 adults (>=40 years old) with available self-reported
      diabetes and NHLU status were analysed. Glycaemic index markers, including FPG
      and HbA1c, were assessed via laboratory analysis from serum blood samples.
      Logistic regression models were fitted to determine optimal thresholds for FPG
      and HbA1c to predict NHLU status. RESULTS: Compared with those without NHLU, NHLU
      patients were older, male, had higher rates of diabetes, were more likely to take
      insulin, and had lower total cholesterol. Youden's Index for NHLU identified the
      optimal FPG threshold as 117.7mg/dl (sensitivity: 33.5%; specificity: 82.6%). The
      optimal HbA1c threshold was 5.9% (sensitivity: 43.2%; specificity: 77.3%). HbA1c
      (Odds ratio (OR) 2.44, 95% Confidence Interval (CI) 1.96-3.05; Area under curve
      (AUC) 0.62) was a stronger discriminator of NHLU compared to FPG (OR 2.19; 95%CI
      1.57-3.05; AUC 0.60). CONCLUSION: This study identified glycaemic thresholds for
      suspicion of NHLU development that are lower than the glucose goal levels
      recommended as optimal by the American Diabetes Association. Health professionals
      should be aware of these glycaemic indices when screening patients with diabetes
      for NHLU. Future longitudinal and validation studies are necessary to better
      discern the ideal glycaemic index thresholds to identify NHLU.

PMID- 29641345
TI  - Transurethral resection of prostate and bleeding: A prospective randomized,
      double blind, placebo controlled trial to see efficacy of short term use of
      Finasteride and Dutasteride on operative blood loss and prostatic micro-vessel
      density.
AB  - OBJECTIVE: To determine the efficacy of short duration use of finasteride and
      dutasteride prior to transurethral resection of prostate (TURP) on intraoperative
      blood loss and microvessel density (MVD) of prostate stroma and suburethral
      tissues in benign prostatic hyperplasia (BPH) Methods: This study includes 450
      patients who were planned for TURP. They were prospectively randomized into three
      groups (150 patients each). Group 1 received placebo, group 2 received
      finasteride 5 mg/day and group 3 patients received dutasteride 0.5 mg/day for 4
      weeks prior to surgery. The total blood loss, requirement of blood, and MVDs in
      prostate stroma and suburethral tissues were calculated in each patient and then
      compared among three groups. RESULTS: There was significant reduction in less
      mean blood loss, blood loss/time, and total blood loss per gram of resected
      tissue in finasteride and dutasteride group compared to placebo. Prostate stromal
      and suburethral MVDs were significantly higher compared to placebo. Blood
      transfusion was required in 9.3%, 2.7%, and 2% of the patients, respectively
      (p=0.004). However, no statistically significant differences were observed
      between finasteride and dutasteride groups for these parameters (p >0.05). The
      weight of resected prostate, operating time, and amount of irrigation fluid used
      did not show any significant difference between the three groups. CONCLUSION:
      Short-term pretreatment with finasteride and dutasteride has similar efficacy and
      significantly reduces perioperative bleeding during TURP and has minimal negative
      impact on sexual function. According to our findings, a 4 weeks' prior
      administration of 5-ARIs may reduce operative blood loss and prostatic MVD in
      TURP, thus potentially decreasing blood loss- related complications and the
      requirement of blood transfusion.

PMID- 29641346
TI  - The Impact of Thiazides and Potassium Citrate on Bone Mineral Density Evaluated
      by CT Scan in Stone Formers.
AB  - INTRODUCTION: Thiazides and citrate prevent kidney stones and improve bone
      mineral density (BMD). The objective of this study was to opportunistically
      utilize the noncontrast CT (NCCT) scan used for stone detection to identify those
      with low BMD and follow the impact of potassium citrate and thiazides on
      longitudinal BMD measurements. MATERIALS AND METHODS: A retrospective analysis
      was performed on 299 kidney stone patients treated with thiazides and/or
      potassium citrate for a minimum of 1 year. For each patient, BMD was estimated at
      L1 with CT attenuation measured in HU. A level of 160 HU was chosen to
      distinguish normal from low BMD. Pairwise t-test was used to compare the
      continuous outcomes before and after treatment for the whole cohort and the low
      BMD subgroup. Linear regression was performed to find if any association exists
      between the duration of follow-up and the changes in HU. A matched pair t-test
      was performed to compare among the medications used and the impact of their doses
      on the HU outcomes. RESULTS: Patients with low BMD (HU <160) comprised (n = 186,
      62.2%) the cohort. A total of 16.1% normalized after 1 year of treatment and 68%
      had an increase in HU. The mean change in HU was 8.6 (p = 0.0001). Linear
      regression demonstrated no association between the duration of treatment and the
      HU changes (p = 0.64). Hydrochlorothiazide (HCTZ) 50 mg was more effective at
      improving BMD (HU +19.7, p = 0.04) compared with 25 mg (+2.9) or 12.5 mg (HU
      +6.4). Majority of the low BMD subgroup were either postmenopausal women (n = 88)
      or men with age older than 60 (n = 74) and both showed a significant increase in
      HU (3.125, 10.731), p-value (0.0453, 0.0007), respectively. CONCLUSION: Stone
      health and bone health are synergistic. The impact of thiazides and citrates on
      BMD can be monitored opportunistically with the NCCT scan.

PMID- 29641347
TI  - Editorial Comment on: Natural History of Conservatively Managed Ureteral Stones:
      Analysis of 6600 Patients by Yallappa et al.

PMID- 29641348
TI  - Retroperitoneal Single Port Versus Transperitoneal Multiport Donor Nephrectomy: A
      Prospective Randomized Control Trial.
AB  - BACKGROUND: Laparoscopic donor nephrectomy (LDN) converted a retroperitoneal (RP)
      procedure into a transperitoneal (TP) operation with reports of bowel and solid
      organ injuries leading to mortality in occasional cases. Laparoscopic RP donor
      nephrectomy can reduce these risks but never became popular because of the muscle
      cutting approach. Lumbotomy incision can be used to approach retroperitoneum by
      incising fascial planes, eliminating disadvantages of the RP approach. This
      report compares the outcomes of the standard multiport TP LDN with translumbar
      laparoendoscopic single-site donor nephrectomy (LESS-DN). METHODS: Between
      January 2016 and June 2017, 50 voluntary kidney donors out of 267 donors were
      randomized to undergo LESS-DN vs LDN. Donors with body mass index >=30 kg/m2,
      multiple renal arteries, and right-sided nephrectomy were excluded from the
      study. Postoperative pain, duration of surgery, length of graft vessels and
      ureter, warm ischemia time, intraoperative blood loss, incision length,
      convalescence period, duration of hospital stay, and recipients' creatinine at
      discharge were compared among both the groups. Pain assessment was done using
      visual analogue scale (VAS). RESULTS: The RP group experienced lesser pain (VAS
      score 0.3 +/- 0.3 vs 1.1 +/- 0.0, p = 0.000), lesser analgesic requirement (186
      +/- 51.07 mg vs 254 +/- 62.7 mg, p = 0.000), and faster convalescence (7.0 +/-
      3.0 days vs 10.7 +/- 3.3 days, p = 0.00) related to smaller cumulative incision
      (7.8 +/- 0.8 cm vs12.4 +/- 2.0 cm, p = 0.00), and had reduced operative time (142
      +/- 26.2 minutes vs 170.8 +/- 34.75 minutes, p = 0.001) and blood loss. Other
      recorded parameters were similar in both the groups. CONCLUSIONS: The single port
      RP approach significantly reduced postoperative pain and hastened recovery when
      compared with the TP approach. Converting to a RP approach presents an
      opportunity for surgeons to further reduce morbidity associated with the donor
      nephrectomy.

PMID- 29641350
TI  - Editorial Comment on: Worldwide Use of Antiretropulsive Techniques: Observations
      from the Clinical Research Office of the Endourological Society Ureteroscopy
      Global Study by Saussine et al.

PMID- 29641349
TI  - Salivary Neutrophil Gelatinase-Associated Lipocalin Sampling Feasibility in Acute
      Renal Colic.
AB  - PURPOSE: Neutrophil gelatinase-associated lipocalin (NGAL) levels in the serum
      and urine are predictive biomarkers of acute kidney injury with correlation to
      complication and survival in major surgery. Salivary levels of NGAL during acute
      renal colic may reflect the degree of renal injury as it appears in different
      compartments encompassing body response in time perspective. Our aim is to
      evaluate and examine the feasibility and correlation of salivary NGAL with serum
      and urine levels in acute renal colic event. MATERIALS AND METHODS: A prospective
      controlled study of all patients presenting to the emergency room with acute
      renal colic event diagnosed with single ureteral stone obstruction by noncontrast
      CT. Saliva, urine, and blood samples were collected in patients and a control
      group during the first morning of admission. RESULTS: The study groups consisted
      of 44 patients and 13 controls, mean age 47 +/- 15 years, body mass index 29 +/-
      6, mean stone size 6 +/- 4 mm, mean creatinine levels 1.3 +/- 0.7 mg/dL, mean
      white blood count 10,900 +/- 3100 counts per field, and C-reactive protein 29 +/-
      55. Serum (190 +/- 120 ng/mL vs 81 +/- 24; p < 0.001) and predominantly salivary
      (474 +/- 185 vs 328 +/- 134 ng/mL; p < 0.05) NGAL levels were significantly
      elevated in patients compared with controls. CONCLUSIONS: Salivary NGAL sampling
      is feasible during the acute phase of renal colic. High levels of salivary NGAL
      are observed in a single sampling during acute ureteral stone obstruction and may
      advance clinical decision-making.

PMID- 29641351
TI  - How Accurate Are We in Estimating True Stone Volume? A Comparison of Water
      Displacement, Ellipsoid Formula, and a CT-Based Software Tool.
AB  - INTRODUCTION: To compare the accuracy and reliability of stone volume estimated
      by ellipsoid formula (EFv) and CT-based algorithm (CTv) to true volume (TV) by
      water displacement in an in vitro model. MATERIALS AND METHODS: Ninety stone
      phantoms were created using clay (0.5-40 cm3, 814 HU +/-91) and scanned with CT.
      For each stone, TV was measured by water displacement, CTv was calculated by the
      region-growing algorithm in the CT-based software AGFA IMPAX Volume Viewer, and
      EFv was calculated by the standard formula pi * L * W * H * 0.167. All
      measurements were repeated thrice, and concordance correlation coefficient (CCC)
      was calculated for the whole group, as well as subgroups based on volume (<1.5
      cm3, 1.5-6 cm3, and >6 cm3). RESULTS: Mean TV, CTv, and EFv were 6.42 cm3 +/-
      6.57 (range: 0.5-39.37 cm3), 6.24 cm3 +/- 6.15 (0.48-36.1 cm3), and 8.98 cm3 +/-
      9.96 (0.49-47.05 cm3), respectively. When comparing TV to CTv, CCC was 0.99 (95%
      confidence interval [CI]: 0.99-0.995), indicating excellent agreement, although
      TV was slightly underestimated at larger volumes. When comparing TV to EFv, CCC
      was 0.82 (95% CI: 0.78-0.86), indicating poor agreement. EFv tended to
      overestimate the TV, especially as stone volume increased beyond 1.5 cm3, and
      there was a significant spread between trials. CONCLUSIONS: An automated CT-based
      algorithm more accurately and reliably estimates stone volume than does the
      ellipsoid formula. While further research is necessary to validate stone volume
      as a surrogate for stone burden, CT-based algorithmic volume measurement of
      urinary stones is a promising technology.

PMID- 29641352
TI  - Analysis of Mechanical Forces Used During Laparoscopic Training Procedures.
AB  - OBJECTIVE: To assess the significance of a surgeon's experience on the mechanical
      forces applied to tissues through laparoscopic instruments. MATERIALS AND
      METHODS: A total of 34 participants were enrolled into the study (8 experts, 10
      intermediates, and 16 novices). Laparoscopic graspers with a sensing module to
      detect load were used by participants to carry out six ex vivo tasks: to grasp a
      porcine ureter in three positions either 1, 5, or 10 times, in turn, with both
      dominant and nondominant hands. The data were logged and recorded by a custom
      data acquisition software to calculate the peak force (Fmax) and mean force
      (Frms). RESULTS: Significant correlation was observed between Fmax and Frms
      (Pearson correlation, r = 0.97, p < 0.0005). No statistical significant
      difference was observed when comparing the effect of the three different tasks on
      peak force (F(2,1084) = 0.28, p = 0.753). There was a statistically significant
      difference in mechanical forces applied with those more experienced applying
      consistently lower mechanical forces (F(2,1084) = 21.36, p < 0.0005). In
      individual training groups, the effect of dominant hand was significant in the
      novice (significantly lower, F(1,510) = 6.70, p = 0.010) and consultants
      (significantly higher, F(1,250) = 9.601, p < 0.020) with the intermediate group
      showing no significant difference between the hands. CONCLUSION: Outcomes have
      suggested a relationship between the training level of the surgeon and the forces
      imparted on the tissue. This demonstrates a need for further training in surgeons
      until a consistent low force can be applied to tissues. Whether such measures
      could be used as an indicator of surgeon proficiency is unclear; however, it has
      the potential to be used to determine whether more training is needed for
      surgeons.

PMID- 29641354
TI  - Editorial Comment on: In Vitro Evaluation of Single-Use Digital Flexible
      Ureteroscopes: A Practical Comparison for Patient-Centered Approach (From:
      Marchini GS, Batagello CA, Monga M, et al. J Endourol 2018;32:184-191).

PMID- 29641353
TI  - Does Retrograde Treatment of Upper Urinary Tract Stones Necessitate Postoperative
      Upper Urinary Tract Drainage? Conclusions from More Than 500 Single Center
      Consecutive Cases.
AB  - BACKGROUND AND PURPOSE: Temporary drainage of the upper urinary tract after
      ureterorenoscopy for the treatment of urinary stones is almost a routine in
      endourologic practice. In these cases, a Double-J stent (DJS) is left for 7 or
      more days. In borderline cases, a ureteral catheter attached to the urethral
      catheter may be left for 24-48 hours. In some situations, tubeless approach is
      possible. The purpose of this study was to evaluate the necessity and immediate
      postoperative implications of upper tract drainage by comparing complications and
      symptoms at the immediate postoperative period in these three groups of patients.
      MATERIALS AND METHODS: A database of 516 consecutive patients who underwent
      ureterorenoscopy for ureteral and/or renal stones between October 2014 and
      September 2016 was retrospectively evaluated. The cohort was divided according to
      postoperative drainage type of the upper urinary tract. The data consisted of
      demographic parameters, stone location, number and burden, severity of
      preoperative obstruction, and postoperative complications. Symptoms at the
      immediate postoperative period, assessed by visual analog scale (VAS) score,
      frequency, and type of analgesics used, were evaluated and compared. Categorical
      dependent variables were evaluated using chi-square or Spearman's correlation
      tests, whereas continuous dependent variables were analyzed using Pearson
      correlation analysis. RESULTS: There were 196 (38%) tubeless, 214 (41%) UC, and
      106 (21%) DJS cases. Patients who were drained with DJS at the end of the
      procedure were significantly with higher stone volume (p < 0.005), higher stone
      density (p < 0.005), and with more severe preoperative obstruction (p < 0.005).
      Postoperative complications (infection, stone-street, and acute renal failure),
      mean VAS score, or analgesics used were not different in the three subgroups.
      CONCLUSIONS: A tubeless approach is safe in properly selected cases. There is no
      difference in postoperative course compared with drained groups. Tubeless
      procedures may facilitate an outpatient approach for treatment of upper urinary
      tract stones.

PMID- 29641355
TI  - Editorial Comment on: Micro-Costing Analysis Demonstrates Comparable Costs for
      LithoVue Compared to Reusable Flexible Fiberoptic Ureteroscopes by Taguchi et al.

PMID- 29641356
TI  - Monopolar Transurethral Enucleo-Resection of the Prostate Versus Holmium Laser
      Enucleation of the Prostate: A Canadian Novel Experience.
AB  - OBJECTIVE: To study the functional outcome of patients undergoing transurethral
      enucleation and resection of the prostate (TUERP) vs patients undergoing holmium
      laser enucleation of the prostate (HoLEP) in men with bladder outlet obstruction.
      MATERIALS AND METHODS: We retrospectively analyzed our prospectively collected
      database of two groups of patients. Twenty-four patients underwent TUERP (group
      1), and 27 underwent HoLEP (group 2). Preoperative characteristics, intervention
      parameters, postoperative functional outcomes, uroflowmetry, and complications
      were collected. RESULTS: Mean prostate size in groups 1 and 2 were 87.2 and 93.5
      cc, respectively. The mean duration of surgery was 110 minutes in group 1 and 136
      minutes in group 2. In group 1, prostate-specific antigen (PSA) dropped from 4.4
      to 1.2 ng/cc after 12 months. International Prostate Symptom Score (IPSS) was
      3.75 at 12 months with a preoperative value of 20.9. With respect to maximum
      urinary flow rate (Qmax), it increased to 21.8 mL/s from a preoperative value of
      6.4 mL/s. In group 2, the PSA dropped from 7.6 to 1.3 ng/cc. IPSS dropped from
      22.3 to 3.8, Qmax increased from 7.7 to 22.5 mL/s. Hemoglobin, complications, and
      all studied parameters were not statistically significant between both groups.
      CONCLUSION: In this study, TUERP was safe and efficacious in benign prostatic
      hyperplasia patients with large glands. Modifications can be implemented on the
      standard transurethral resection of the prostate technique to treat patients with
      prostate sizes >70 cc.

PMID- 29641357
TI  - Does cross-cultural communication training for physicians improve pediatric
      asthma outcomes? A randomized trial.
AB  - OBJECTIVE: Adverse cross-cultural interactions are a persistent problem within
      medicine impacting minority patients' use of services and health outcomes. To
      test whether 1) enhancing the evidence-based Physician Asthma Care Education
      (PACE), a continuing medical education program, with cross cultural communication
      training (PACE Plus) would improve the asthma outcomes of African American and
      Latino/Hispanic children; and 2) whether PACE is effective in diverse groups of
      children. METHODS: A three-arm randomized control trial was used to compare PACE
      Plus, PACE, and usual care. Participants were primary care physicians (n = 112)
      and their African American or Latino/Hispanic pediatric patients with persistent
      asthma (n = 867). The primary outcome of interest included changes in emergency
      department visits for asthma overtime, measured at baseline, and 9 and 21 months
      following the intervention. Other outcomes included hospitalizations, asthma
      symptom experience, caregiver asthma-related quality of life, and patient
      provider communication measures. RESULTS: Over the long term, PACE Plus
      physicians reported significant improvements in confidence and use of patient
      centered communication and counseling techniques (p < 0.01) compared to PACE
      physicians. No other significant benefit in primary and secondary outcomes was
      observed in this trial. CONCLUSION: PACE Plus did not show significant benefit in
      asthma-specific clinical outcomes. More trials and multi-component strategies
      continue to be needed to address complex risk factors and reduce disparities in
      asthma care. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01251523 December 1,
      2010.

PMID- 29641358
TI  - H3N2 influenza viruses in humans: Viral mechanisms, evolution, and evaluation.
AB  - Annual seasonal influenza vaccines are composed of two influenza A strains
      representing the H1N1 and H3N2 subtypes, and two influenza B strains representing
      the Victoria and Yamagata lineages. Strains from these Influenza A and Influenza
      B viruses currently co-circulate in humans. Of these, strains associated with the
      H3N2 subtype are affiliated with severe influenza seasons. H3N2 influenza viruses
      pre-dominated during 3 of the last 5 quite severe influenza seasons. During the
      2016/2017 flu season, the H3N2 component of the influenza vaccine exhibited a
      poor protective efficacy (~28-42%) against preventing infection of co-circulating
      strains. Since their introduction to the human population in 1968, H3N2 Influenza
      viruses have rapidly evolved both genetically and antigenically in an attempt to
      escape host immune pressures. As a result, these viruses have added numerous N
      linked glycans to the viral hemagglutinin (HA), increased the overall net charge
      of the HA molecule, changed their preferences in receptor binding, and altered
      the ability of neuraminidase (NA) to agglutinate red blood cells prior to host
      entry. Over time, these adaptations have made characterizing these viruses
      increasingly difficult. This review investigates these recent changes in modern
      H3N2 influenza viruses and explores the methods that researchers are currently
      developing in order to study these viruses.

PMID- 29641359
TI  - The Frequency of Metabolic Syndrome and Serum Osteopontin Levels in Survivors of
      Childhood Acute Lymphoblastic Leukemia.
AB  - PURPOSE: Metabolic syndrome (MetS) and obesity have increasingly been reported in
      survivors of childhood cancer. Osteopontin (OPN) is primarily synthesized in
      adipose tissue and is thought to have a role in obesity and the development of
      insulin resistance (IR). The aim of this study was to investigate the frequency
      of MetS in survivors of acute lymphoblastic leukemia (ALL) and to establish the
      relationship between serum OPN levels and anthropometric measurements and glucose
      metabolism. METHODS: A total 50 survivors of ALL (median age: 10.5 years; post
      treatment interval 4.54 +/- 2.48 years), and 20 healthy children (median age: 11
      years) were included in the study. Anthropometric measurements were taken, and
      serum glucose, insulin, homeostasis model assessment and IR index (HOMA-IR
      index), lipoprotein, thyroid hormone levels, and OPN levels were measured.
      RESULTS: Twenty-one (42%) survivors were overweight/obese, 2 (5.1%) survivors had
      MetS, 7 (14%) survivors had IR, and 19 (38%) survivors had dyslipidemia. Fasting
      insulin levels and HOMA-IR of the overweight/obese survivors were significantly
      higher than those of the normal-weight survivors (p < 0.05 and p < 0.01) and
      control group (p < 0.01 and p < 0.01). The serum OPN level was significantly
      lower in the overweight/obese survivor than in the normal-weight survivor and
      control group (37.42 ng/mL [range, 27.32-62.07], 69.02 ng/mL [range, 40.29
      88.21], and 85.7 ng/mL [range 67.7-102.3]; p < 0.01, p < 0.001, respectively).
      Serum OPN levels were inversely correlated with anthropometric measurements and
      HOMA-IR index in all the subjects. CONCLUSION: Our results showed that obesity
      and IR are associated with decreased serum OPN levels in childhood survivors of
      ALL.

PMID- 29641360
TI  - Facing the Maze: Young Cancer Survivors' Return to Education and Work-A
      Professional Expert Key Informant Study.
AB  - PURPOSE: An insufficient transition to normal life after cancer treatment in
      adolescent and young adults (AYAs) may lead to decreased occupational and
      educational opportunities throughout a survivor's lifespan. Key informant
      interviews were used to access unique knowledge of the healthcare, educational,
      and social systems. METHODS: We used key informant interviews with professionals
      representing disciplines from healthcare, educational, and social systems (n =
      15). Informants were recruited through purposive sampling and snowball sampling.
      Interviews were analyzed thematically using Malterud's Systematic Text
      Condensation and verified by member checking. RESULTS: We found four major
      themes: the impact of late effects, navigating the system, social reintegration,
      and the drive of youth. Although legal frameworks are often in place to assist
      AYA cancer survivors, navigating the public, educational, and social systems is a
      complex task and many AYAs do not have the required skill set or energy.
      Furthermore, AYA survivors often feel different from their peers and
      misunderstood by their surroundings, which may hinder reintegration into normal
      social life. CONCLUSIONS: In Scandinavia, healthcare and education are free of
      charge with equal access for all, primarily funded by government taxes.
      Therefore, insurance status and tuition fees should not constitute barriers for
      returning to education and work. However, this study finds that the public and
      educational systems are complex to navigate, and that AYAs face trouble
      mobilizing the energy to receive needed support.

PMID- 29641361
TI  - Aerosolization of Zn-DTPA Decorporation Agent Using Jet and Ultrasonic
      Nebulizers.
AB  - BACKGROUND: Chelating agents such as diethylenetriamine pentaacetic acid (DTPA)
      can be used as a decorporation drug in the zinc (Zn) form to treat internal
      radioactive contamination after exposure to plutonium or americium in a nuclear
      accident. Although Zn-DTPA is normally administered intravenously, inhalation of
      Zn-DTPA in aerosol form is a better route for direct delivery to the lungs. This
      work investigates the feasibility of synthesizing Zn-DTPA from three common
      chemicals and aerosolizing it using a jet or ultrasonic nebulizer. METHODS: The
      particle size distribution (PSD) of this decorporation agent at different
      concentrations were tested in vitro using two different methods: inertial
      impaction and aerodynamic time of flight. The particles were generated using
      either a jet nebulizer or an ultrasonic nebulizer. Two parameters, namely the
      mass median aerodynamic diameter and the geometric standard deviation, were
      assessed to determine the PSD of the generated aerosols. These parameters were
      obtained for different concentrations of Zn-DTPA using both nebulizers. RESULTS
      AND CONCLUSIONS: Zn-DTPA was successfully synthesized for decorporation purposes.
      Aerosol particles within the inhalable range were successfully generated by both
      nebulizers from four different concentrations of Zn-DTPA. It was found that the
      medication concentration did not affect the PSD of Zn-DTPA. The ultrasonic
      nebulizer was observed to produce a slightly larger aerosol particle size and
      required slightly longer treatment periods to deliver an effective dose to the
      lungs when compared with the jet nebulizer. Both nebulizers can be sustainably
      run to administer the agent for effective decorporation treatment of a large
      population after any major nuclear accident.

PMID- 29641362
TI  - Effect of Topical Lidocaine Patch on Postoperative Pain Management in
      Laparoscopic Appendectomy: A Randomized, Double-Blind, Prospective Study.
AB  - BACKGROUND: Adequate pain control is a major concern in the immediate
      postoperative period. In multiple strategies for postoperative pain management,
      topical analgesics have significant advantages of minimizing severe side effects
      caused by oral and parenteral administration and drug-drug interactions.
      Therefore, we studied the effect of lidocaine patch on postoperative pain control
      in laparoscopic appendectomy. PATIENTS AND METHODS: This randomized double-blind
      prospective controlled study enrolled 40 acute appendicitis cases that were
      treated by laparoscopic appendectomy and randomly divided into two groups.
      Lidocaine patches containing lidocaine 175 mg was applied to the umbilical trocar
      site of each patient, and pain intensity was assessed with the visual analog
      scale every 6 hours up to 48 hours after laparoscopic appendectomy. RESULTS:
      There was no significant difference in age, gender, body mass index, the American
      society of anesthesiologists score, comorbidity, or underlying disease between
      the lidocaine patch and control groups. The postoperative pain scores were lower
      in the lidocaine patch group than in the control group, but statistical
      significance was not noted at the trocar site or the right lower quadrant of the
      abdomen (P = .320 and P = .903, respectively). The mean amounts of pethidine used
      after surgery were significantly smaller in the lidocaine patch group than in the
      control group (0.10 +/- 0.31 mg versus 0.25 +/- 0.79 mg, P < .001). CONCLUSIONS:
      The results of this study suggest that lidocaine patch application to the trocar
      site after laparoscopic appendectomy may have a positive effect on the management
      of postoperative pain and can eliminate the need to inject additional analgesics
      for further postoperative pain control.

PMID- 29641363
TI  - A Single Tertiary Center 10-Year Experience in the Surgical Management of
      Gastrointestinal Bezoars.
AB  - BACKGROUND: Gastrointestinal (GI) bezoars are the most common foreign bodies
      causing obstruction in the GI tract. They are frequently seen following upper GI
      tract surgery and surgical intervention is required often. The aim of this study
      is to describe the surgical management of GI bezoars. MATERIALS AND METHODS: A
      retrospective cohort study, including all patients diagnosed with bezoars between
      May 2008 and May 2017, was conducted. Patient charts were reviewed, and
      demographics, clinical, surgical, and postoperative data were collected and
      analyzed. RESULTS: Forty-five patients were included, with a mean age of 62.04
      years (Range 18-91). Thirty patients underwent previous surgery (66.6%), most
      commonly surgical interventions for peptic ulcer disease (22 patients, 73.3%).
      Obstruction was most common in the ileum (27 patients, 60%). Thirty-nine patients
      (86.7%) required surgical intervention. Laparoscopy was attempted in 20 patients
      (51.2%), but conversion to open procedure was required in 11 patients (55%).
      Postoperative complication rate was 41%. No preoperative factors were found to be
      correlated with postoperative complications. Postoperative complications were
      associated with a longer length of stay (P = .006) and a higher readmission rate
      (P = .04). Patients treated with laparoscopy tended to have a lower BMI (P =
      .04), less previous surgeries (P = .04), and a bezoar located more proximally (P
      = .03), however, laparoscopy showed no benefit in complications rate,
      readmissions, and length of stay. CONCLUSIONS: GI bezoars require surgical
      intervention at high rates. Postoperative complications are common. Completion of
      an upper GI endoscopy is important and should be performed at an early stage of
      management.

PMID- 29641364
TI  - Thoracoscopic Repair of Congenital Diaphragmatic Hernia After Extracorporeal
      Membrane Oxygenation: Feasibility and Outcomes.
AB  - INTRODUCTION: Thoracoscopic repair of congenital diaphragmatic hernia (CDH) has
      been associated with faster recovery, earlier extubation, and decreased
      morbidity. Nevertheless, thoracoscopic repair is rarely attempted in the post
      extracorporeal membrane oxygenation (ECMO) patient. Commonly cited reasons for
      not attempting thoracoscopy include concerns that the patients' respiratory
      status is too tenuous to tolerate insufflation pressures or that presumed defect
      size is so large that it precludes thoracoscopic repair. Our purpose is to review
      our experience with post-ECMO thoracoscopic CDH repair and evaluate the success
      of this approach. METHODS: We performed retrospective analysis of attempted
      thoracoscopic CDH repairs after ECMO decannulation at our institution from 2001
      to 2015. Primary outcome was rate of conversion. Secondary outcomes were
      intraoperative end-tidal CO2, time to extubation, and rate of recurrence.
      RESULTS: We identified 21 post-ECMO patients in whom thoracoscopic CDH repair was
      attempted. Thoracoscopic repair was successfully completed in 28%. No patients
      had reported intolerance to insufflation at 3-7 mmHg. Average end-tidal CO2 at 15
      operative minutes was 36.9 mmHg in the thoracoscopic group versus 50.7 mmHg in
      the open group and at 60 minutes was 34.25 mmHg versus 45.6 mmHg, respectively.
      One patient in the thoracoscopic group died and 1 experienced a large
      pneumothorax. In the converted group there was one clinically significant
      pneumothorax and three pleural effusions. Survivors after thoracoscopy were
      extubated an average of 5.6 +/- 2.6 days after surgery versus 19.4 +/- 10 days in
      the converted group (P < .05). Recurrence rates at last follow-up were equal
      between the two groups at 20%. CONCLUSIONS: Thoracoscopic CDH repair is both safe
      and feasible after ECMO with no increase in operative morbidity or mortality.
      Insufflation pressures of 3-7 mmHg are well tolerated without undue increase in
      end-tidal CO2. When compared to conversion cases, thoracoscopic repair is
      associated with significantly decreased time to extubation with no difference in
      recurrence.

PMID- 29641365
TI  - Endoscopic Biliary Drainage Versus Percutaneous Transhepatic Biliary Drainage in
      Patients with Resectable Hilar Cholangiocarcinoma: A Systematic Review and Meta
      Analysis.
AB  - BACKGROUND: Hilar cholangiocarcinoma (HCCA) is a rare tumor, usually associated
      with obstructive jaundice and unfavorable prognosis. Obstructive jaundice can
      affect the liver, kidney, heart, and the immune system of the patients.
      Currently, controversy exists in whether preoperative biliary drainage (PBD) is
      of any benefit to the patients, and the best way for PBD in patients with
      resectable HCCA of malignant biliary obstruction remains to be determined.
      OBJECTIVES: To compare the clinical outcomes and effectiveness of endoscopic
      biliary drainage (EBD) treatment with those of percutaneous transhepatic biliary
      drainage (PTBD) treatment in patients with malignant biliary obstruction caused
      by resectable HCCA. MATERIALS AND METHODS: The databases including MEDLINE,
      EMBASE, PubMed, CBM (China Biological Medicine Database), and CNKI were employed
      to identify the clinic trials on EBD versus PTBD for malignant biliary
      obstruction associated with resectable HCCA from January 2008 to October 2017. A
      systematic review and meta-analysis were carried out. RESULTS: Six trials were
      identified and included in this study. Overall, the differences in technical
      success rate, R0 resection, incidence of total complication after resection,
      postoperative hospitalization time, resection time, and recurrence were not
      statistically significant between the EBD group and PTBD group (all P > .05).
      However, the incidence of total complications after EBD treatment is higher than
      that after PTBD treatment (P < .05). CONCLUSION: For patients with obstructive
      jaundice associated with HCCA, current evidence indicate no superiority of PTBD
      over EBD regarding clinical feasibility and success rate, but data suggest a
      better clinical safety of PTBD compared with EBD in short-term postoperation. In
      long-term evaluation, the differences in clinical outcomes are not statistically
      significant between PTBD and EBD.

PMID- 29641366
TI  - The Role of Prophylactic Endoscopic Sphincterotomy for Prevention of
      Postoperative Bile Leak in Hydatid Liver Disease: A Randomized Controlled Study.
AB  - BACKGROUND: Bile leak is the main cause of morbidity and mortality after surgery
      for hydatid liver cysts. Aim was to assess the role of prophylactic endoscopic
      sphincterotomy (ES) in reducing postoperative bile leak in patients undergoing
      partial cystectomy. METHODS: Fifty-four patients with hepatic hydatid cyst met
      inclusion criteria, 27 were excluded or declined to participate. Twenty-six women
      and 28 men (mean age 44.6 +/- 10.1, range: 22-61 years) were randomly assigned to
      either group I with ES (n = 27) or group II without ES (n = 27). RESULTS:
      Demographics and clinical, laboratory, and radiological characteristics of cysts
      were not statistically different between two groups. Group I had a significant
      decrease in bile leak rate compared with group II (11.1% versus 40.7%, P = .013),
      with significantly shorter duration of hospital stay (P < .0001). Biliary fistula
      in group I had significantly lower daily output (100 mL/day versus 350 mL/day)
      with gradual reduction till stoppage of leak in 3-4 days without intervention.
      Biliary fistula in group II had a significantly higher need for biliary
      intervention through postoperative endoscopic retrograde cholangiopancreatography
      with ES compared with biliary fistula in group I (FEP = .002), with significantly
      longer mean time of fistula closure (P = .011) and longer time to drain removal
      (P < .0001). Nonbiliary complications were comparable between two groups.
      CONCLUSION: Prophylactic ES provides significant reduction in postoperative bile
      leak rate with shorter hospital stay after partial cystectomy of hydatid cyst.
      Biliary fistula in patients with ES has significantly lower daily output with
      shorter time of drain removal and shorter time to closure than patients without
      ES.

PMID- 29641367
TI  - The Case for Simulation-Based Mastery Learning Education Courses for Practicing
      Surgeons.
AB  - INTRODUCTION: Pediatric surgeons rely on simulation courses to develop skills for
      safe minimally invasive repair of complex congenital anomalies. The majority of
      minimally invasive surgery (MIS) training courses occur during short "exposure
      courses" at annual conferences. Little data are available to support the benefit
      of these courses relative to the safe implementation of new skills. The purpose
      of this article is to determine the impact of an exposure course for advanced
      neonatal MIS on self-perceived comfort levels with independent performance of
      advanced MISs. METHODS: Participants of a 4-hour hands-on course for neonatal MIS
      were surveyed regarding clinical practices and pre- and post-training perceived
      "comfort levels" of MIS skills for thoracoscopic esophageal atresia with
      tracheoesophageal fistula (tTEF) repair, thoracoscopic left upper lobe pulmonary
      lobectomy (tLobe), and laparoscopic duodenal atresia (lapDA) repair. Descriptive
      analyses were performed. RESULTS: Seventeen participants completed pre- and
      postcourse surveys. The majority of participants had no prior experience with
      tLobe (59%) or lapDA (53%), and 35% had no experience with tTEF repair.
      Similarly, the majority were "not comfortable" with these procedures. After the
      short course, the majority of surgeons reported that they were "likely to
      perform" these operations within 6 months, despite low levels of baseline
      experience and comfort levels. CONCLUSION: An exposure training course led to
      immediate perception of increased skills and confidence. However, these courses
      typically do not provide basic tenets of expert performance that demands
      deliberate practice. Future course design should transition to a mastery learning
      framework wherein regular skill assessments, milestones, and unlimited education
      time are prioritized before implementation of the new skills.

PMID- 29641368
TI  - From Laparoscopic Pyeloplasty to Robot-Assisted Laparoscopic Pyeloplasty in
      Primary and Reoperative Repairs for Ureteropelvic Junction Obstruction in
      Children.
AB  - PURPOSE: Robot-assisted laparoscopic pyeloplasty (RALP) and laparoscopic
      pyeloplasty (LP) are both minimally invasive surgical options to correct
      ureteropelvic junction obstruction in children. There are limited data reporting
      surgeons' experience of switching from LP to RALP and comparing the outcomes of
      the two procedures. METHODS: We conducted a retrospective study on 63 consecutive
      children who underwent either LP or RALP by the same surgeon in a tertiary center
      from January 2008 to November 2016. LP had been the standard practice until
      January 2014 when it was replaced by RALP in short transition. RESULTS: Thirty
      seven LP and 26 RALP were successfully performed in children aged 2 months to 16
      years. There was no difference between the two groups in age, body weight,
      laterality, clinical presentations, preoperative imagings, primary/reoperative
      repairs. The overall success rates were 34/37 (91.9%) and 25/26 (96.2%) for LP
      and RALP, respectively (P > .05). RALP was associated with shorter length of stay
      (3.1 days versus 4.0 days; P = .03). Surgeon-in-training participation was
      greater in RALP group (P < .001). There was no difference in operative time,
      complication rates, and analgesic requirement between the two groups.
      CONCLUSIONS: Surgeons proficient in LP can adapt quickly to RALP, achieving
      comparable outcomes. Robotic technology may facilitate training on minimally
      invasive pyeloplasty.

PMID- 29641369
TI  - Preliminary Assessment of a Dry-Lab Model for Laparoscopic Percutaneous Inguinal
      Ring Suture Training.
AB  - INTRODUCTION: Laparoscopic percutaneous inguinal ring suturing (PIRS) is a
      valuable technique to repair indirect inguinal hernias in children. The aim of
      the study was to show the preliminary results of training in an easy-to-build dry
      lab model for laparoscopic PIRS technique. MATERIALS AND METHODS: The dry-lab
      model consists of two surgical gloves (being the smaller inside the larger). The
      entry of the glove is tied with a rubber letting a 5-mm trocar within it (optic).
      Carbon dioxide is inflated through the trocar at 8 mmHg pressure. The four long
      fingers of the glove simulate four internal inguinal rings. Eighteen participants
      without significant laparoscopic experience were asked to visualize a video
      showing a laparoscopic PIRS performed in a 4-year-old girl with a right inguinal
      hernia followed by a video showing the same technique performed in our dry-lab
      model. They were then asked to repeat the procedure in each of the four fingers,
      and the procedures were recorded. Two surgeons using the task-specific checklists
      (TSCs), global rating scale of operative performance (GRS), and time for the
      whole procedure evaluated the performance blindly. RESULTS: We found significant
      improvement in median TSC (P < .05) and median GRS each time the procedure was
      repeated (P < .05). There was significant shortening each time the procedure was
      repeated (P < .05), except between the third and fourth finger (P = .068).
      CONCLUSION: Our dry-lab model might be a good option for starting laparoscopic
      PIRS training.

PMID- 29641370
TI  - Laparoscopic-Assisted Transhiatal Esophagogastrectomy Without Thoracic or
      Cervical Access: A Series of One Hundred Three Consecutive Cases.
AB  - AIM: To evaluate short-term and long-term outcomes of laparoscopic-assisted
      transhiatal esophagogastrectomy (LTEG) for treatment of adenocarcinoma of the
      esophagogastric junction (AEG). METHODS: Patients with AEG who underwent
      laparoscopic or open surgery at our department from October 2008 to December 2012
      were enrolled in this retrospective study. Patients' demographics, perioperative
      outcomes, and survival data were collected. RESULTS: A total of 136 patients with
      AEG were enrolled (103 patients underwent laparoscopic surgery and 33 patients
      underwent open surgery). Patient characteristics were comparable between two
      groups in terms of age, gender, tumor-node-metastasis stage, tumor size,
      preoperative complications, and type of surgery. The median operative time was
      longer in laparoscopic group (240 versus 210 minutes, P = .048). However, the
      estimated blood loss was less, and the rate of pleural rupture was lower in
      laparoscopic group (20 versus 70 mL, P < .001 and 18.4% versus 36.4%, P = .033,
      respectively). The rate of patients with pleural rupture requiring prolonged use
      of mechanical ventilation longer than 12 hours (6/31, 19.4%) was higher than that
      of patients without pleural rupture (6/105, 5.7%) (P = .019). The incidence of
      reflux symptoms at postoperative month six was similar in two groups (18.4% in
      laparoscopic group versus 24.2% in open group, P = .468), as well as the use of
      proton pump inhibitors (12.6% versus 15.2%, P = .709). Furthermore, the number of
      lymph nodes harvested (22 versus 25), 2-year cumulative overall survival rates
      (80.4% versus 57.5%), and the median survival times (51.52 months versus 24.24
      months) were similar between two groups (P > .05). CONCLUSION: LTEG is a safe,
      feasible, and oncologically effective procedure for AEG when performed by an
      experienced surgeon. Laparoscopic surgery is associated with a lower risk of
      pleural rupture, but pleural rupture in laparoscopic surgery may cause an adverse
      effect on the recovery of pulmonary function presumably due to tension
      pneumothorax.

PMID- 29641371
TI  - Thoracoscopy Versus Open Surgery for Persistent Ductus Arteriosus and Vascular
      Ring Anomaly in Neonates and Infants.
AB  - BACKGROUND: The aim of our study was to report our experience in thoracoscopy in
      infants and neonates for vascular surgical conditions in neonates and infants and
      to compare our results to open surgery regarding the short-term outcome. PATIENTS
      AND METHODS: We retrospectively reviewed all the patients operated in a single
      institution from 1997 to 2016 for persistent ductus arteriosus (PDA) and vascular
      ring (VR) anomalies. We compared our thoracoscopic series to a historical control
      group operated by open surgery. Data collection from charts and office notes
      included age and weight at surgery, cardiac ultrasound data for PDA, preoperative
      clinical symptoms for VR, type of surgery, operating time, analgesic treatment
      requirements, ventilation status during postoperative course, and early
      complications. RESULTS: The thoracoscopic group included 13 PDA (median age and
      weight at surgery: 34 days and 1800 g) and 11 VR (median age and weight at
      surgery: 8 months and 7000 g). The thoracoscopic group did not differ in
      preoperative symptoms and work-up, operating time, ventilation status, length of
      hospital-stay, and postoperative complications with the group operated on by
      thoracotomy, for either PDA or VR. CONCLUSION: Our short-term results in
      thoracoscopic PDA closure and VR anomalies surgery in neonates and infants are
      comparable to open surgery. Thoracoscopy seems to provide less pain especially
      for neonates and premature babies and allows to decrease the risk for
      postoperative chest wall deformities. Long-term outcome is mandatory to confirm
      these preliminary results.

PMID- 29641373
TI  - Response to Cao et al. re: Comparison of Surgical Outcomes Between Resection and
      Enucleation in Robot-Assisted Laparoscopic Partial Nephrectomy for Renal Tumors
      According to the Surface-Intermediate-Base Margin Score: A Propensity Score
      Matched Study.

PMID- 29641372
TI  - Feasibility of Laparoscopic Resection of Gastrointestinal Stromal Tumor of the
      Stomach.
AB  - BACKGROUND: Gastrointestinal stromal tumors (GISTs) are the most common
      mesenchymal tumors of the gastrointestinal tract. Complete surgical resection of
      localized GISTs is the only chance of cure for patients. Laparoscopic resections
      (LAP) have been widely accepted as a reasonable approach to treat gastric GISTs.
      The current study compares operative outcomes of laparoscopic and open resection
      of gastric GISTs. MATERIALS AND METHODS: We retrospectively reviewed patients
      with primary gastric GISTs who underwent surgical resection between 2003 and
      2015. RESULTS: Of a total of 89 patients, 24 (27%) patients underwent open
      resection (OPEN), and 65 (73%) underwent LAP. LAP or OPEN did not differ with
      respect to gender, body mass index, and age. Median blood loss was significantly
      lower in LAP than in OPEN resection (32.5 mL versus 100 mL, P < .01). Both tumor
      location and median operative time were comparable between LAP and OPEN (108
      versus 108 min, P = .93). Median tumor size in OPEN was significantly larger than
      LAP tumors (6.5 versus 3.8 cm, P < .01). LAP resection yielded a shorter hospital
      stay (3.0 versus 6.0 days P < .01) and lower 30-day readmission rate (17% versus
      0%; P < .01). Complication rates were 9% after LAP and 12% after OPEN (P = .652).
      Two patients in each group died during the study period. Kaplan-Meier analysis
      for overall survival showed no significant difference between LAP and OPEN (P =
      .23). CONCLUSIONS: LAP of gastric GISTs resulted in similar operative time and
      survival rate, but shorter hospital stay compared with open resection.
      Consequently, whenever possible, the laparoscopic approach should be preferably
      used for treatment of gastric GISTs. However, advanced tumor stage might dictate
      the need for open procedure with expected worse results.

PMID- 29641374
TI  - Feasibility of medication monitoring sensors in high risk asthmatic children.

PMID- 29641376
TI  - Subject-Independent ERP-Based Brain-Computer Interfaces.
AB  - Brain-computer interfaces (BCIs) are desirable for people to express their
      thoughts, especially those with profound disabilities in communication. The
      classification of brain patterns for each different subject requires an
      extensively time-consuming learning stage specific to that person, in order to
      reach satisfactory accuracy performance. The training session could also be
      infeasible for disabled patients as they may not fully understand the training
      instructions. In this paper, we propose a unified classification scheme based on
      ensemble classifier, dynamic stopping, and adaptive learning. We apply this
      scheme on the P300-based BCI, with the subject-independent manner, where no
      learning session is required for new experimental users. According to our
      theoretical analysis and empirical results, the harmonized integration of these
      three methods can significantly boost up the average accuracy from 75.00% to
      91.26%, while at the same time reduce the average spelling time from 12.62 to
      6.78 iterations, approximately to two-fold faster. The experiments were conducted
      on a large public dataset which had been used in other related studies. Direct
      comparisons between our work with the others' are also reported in details.

PMID- 29641375
TI  - Postharvest control of anthracnose lesions and its causative agent,
      Colletotrichum musae by some oils.
AB  - Anthracnose of banana is incited by Colletotrichum  musae. It is recognized as
      one the most destructive diseases of mature and immature banana fruits, resulting
      in huge economic losses all over the world. Present research deals with screening
      some oils both in vitro and in vivo for their antifungal activity against
      C.musae. Clove oil (0.1ul/ml) completely arrested the conidial germination and
      mycelial growth of C. musae. Fenugreek and almond oil exhibited significant
      inhibition of mycelial growth, 61% and 57% at a concentration of 2ul/ml. However,
      olive oil was least inhibitory on the test fungi. Clove oil also a showed marked
      reduction in anthracnose lesions on banana fruits, thereby suggesting disease
      control. Scanning electron microscopy revealed severely damaged mycelium and
      conidia. FTIR studies show the presence of important bands representing phenols,
      terpenes, aldehydes, and ketones. Based on our findings; clove, fenugreek and
      almond oil demonstrated fungicidal and fungistatic activities against anthracnose
      pathogen. Hence, these oils can be considered as potential alternatives to
      chemical treatments.

PMID- 29641377
TI  - Cognitive Behavior Classification From Scalp EEG Signals.
AB  - Electroencephalography (EEG) has become increasingly valuable outside of its
      traditional use in neurology. EEG is now used for neuropsychiatric diagnosis,
      neurological evaluation of traumatic brain injury, neurotherapy, gaming,
      neurofeedback, mindfulness, and cognitive enhancement training. The trend to
      increase the number of EEG electrodes, the development of novel analytical
      methods, and the availability of large data sets has created a data analysis
      challenge to find the "signal of interest" that conveys the most information
      about ongoing cognitive effort. Accordingly, we compare three common types of
      neural synchrony measures that are applied to EEG-power analysis, phase locking,
      and phase-amplitude coupling to assess which analytical measure provides the best
      separation between EEG signals that were recorded, while healthy subjects
      performed eight cognitive tasks-Hopkins Verbal Learning Test and its delayed
      version, Stroop Test, Symbol Digit Modality Test, Controlled Oral Word
      Association Test, Trail Marking Test, Digit Span Test, and Benton Visual
      Retention Test. We find that of the three analytical methods, phase-amplitude
      coupling, specifically theta (4-7 Hz)-high gamma (70-90 Hz) obtained from frontal
      and parietal EEG electrodes provides both the largest separation between the EEG
      during cognitive tasks and also the highest classification accuracy between pairs
      of tasks. We also find that phase-locking analysis provides the most distinct
      clustering of tasks based on their utilization of long-term memory. Finally, we
      show that phase-amplitude coupling is the least sensitive to contamination by
      intense jaw-clenching muscle artifact.

PMID- 29641378
TI  - Functional Connectivity Analysis of Mental Fatigue Reveals Different Network
      Topological Alterations Between Driving and Vigilance Tasks.
AB  - Despite the apparent importance of mental fatigue detection, a reliable
      application is hindered due to the incomprehensive understanding of the neural
      mechanisms of mental fatigue. In this paper, we investigated the topological
      alterations of functional brain networks in the theta band (4 - 7 Hz) of
      electroencephalography (EEG) data from 40 male subjects undergoing two distinct
      fatigue-inducing tasks: a low-intensity one-hour simulated driving and a high
      demanding half-hour sustained attention task [psychomotor vigilance task (PVT)].
      Behaviorally, subjects demonstrated a robust mental fatigue effect, as reflected
      by significantly declined performances in cognitive tasks prior and post these
      two tasks. Furthermore, characteristic path length presented a positive
      correlation with task duration, which led to a significant increase between the
      first and the last five minutes of both tasks, indicating a fatigue-related
      disruption in information processing efficiency. However, significantly increased
      clustering coefficient was revealed only in the driving task, suggesting distinct
      network reorganizations between the two fatigue-inducing tasks. Moreover, high
      accuracy (92% for driving; 97% for PVT) was achieved for fatigue classification
      with apparently different discriminative functional connectivity features. These
      findings augment our understanding of the complex nature of fatigue-related
      neural mechanisms and demonstrate the feasibility of using functional
      connectivity as neural biomarkers for applicable fatigue monitoring.

PMID- 29641379
TI  - Contact Pressure and Flexibility of Multipin Dry EEG Electrodes.
AB  - In state-of-the-art electroencephalography (EEG) Silver/Silver-Chloride
      electrodes are applied together with electrolyte gels or pastes. Their
      application requires extensive preparation, trained medical staff and limits
      measurement time and mobility. We recently proposed a novel multichannel cap
      system for dry EEG electrodes for mobile and out-of-the-lab EEG acquisition.
      During the tests with these novel polymer-based multipin dry electrodes, we
      observed that the quality of the recording depends on the applied normal force
      and resulting contact pressure. Consequently, in this paper we systematically
      investigate the influence of electrode-skin contact pressure and electrode
      substrate flexibility on interfacial impedance and perceived wearing comfort in a
      study on 12 volunteers. The normal force applied to the electrode was varied
      between the minimum required force to achieve impedances and a maximum of 4 N,
      using a new force measurement applicator. We found that for a polymer shore
      hardness A98, with increasing normal force, the impedance decreases from and to
      and at frontal hairless and temporal hairy positions, respectively. Similar
      results were obtained for shore A90, A80, and A70. The best compromise of low and
      stable impedances as well as a good wearing comfort was determined for applied
      normal forces between 2 and 3 N using electrodes with shore A98 or A90. Our
      results provide the basis for improved EEG cap designs with optimal wearing
      comfort and recording quality for dry multipin electrodes, which will enable new
      fields of application for EEG.

PMID- 29641380
TI  - A Deep Learning Architecture for Temporal Sleep Stage Classification Using
      Multivariate and Multimodal Time Series.
AB  - Sleep stage classification constitutes an important preliminary exam in the
      diagnosis of sleep disorders. It is traditionally performed by a sleep expert who
      assigns to each 30 s of the signal of a sleep stage, based on the visual
      inspection of signals such as electroencephalograms (EEGs), electrooculograms
      (EOGs), electrocardiograms, and electromyograms (EMGs). We introduce here the
      first deep learning approach for sleep stage classification that learns end-to
      end without computing spectrograms or extracting handcrafted features, that
      exploits all multivariate and multimodal polysomnography (PSG) signals (EEG, EMG,
      and EOG), and that can exploit the temporal context of each 30-s window of data.
      For each modality, the first layer learns linear spatial filters that exploit the
      array of sensors to increase the signal-to-noise ratio, and the last layer feeds
      the learnt representation to a softmax classifier. Our model is compared to
      alternative automatic approaches based on convolutional networks or decisions
      trees. Results obtained on 61 publicly available PSG records with up to 20 EEG
      channels demonstrate that our network architecture yields the state-of-the-art
      performance. Our study reveals a number of insights on the spatiotemporal
      distribution of the signal of interest: a good tradeoff for optimal
      classification performance measured with balanced accuracy is to use 6 EEG with 2
      EOG (left and right) and 3 EMG chin channels. Also exploiting 1 min of data
      before and after each data segment offers the strongest improvement when a
      limited number of channels are available. As sleep experts, our system exploits
      the multivariate and multimodal nature of PSG signals in order to deliver the
      state-of-the-art classification performance with a small computational cost.

PMID- 29641381
TI  - Anomaly Detection of Electromyographic Signals.
AB  - In this paper, we provide a robust framework to detect anomalous
      electromyographic (EMG) signals and identify contamination types. As a first step
      for feature selection, optimally selected Lawton wavelets transform is applied.
      Robust principal component analysis (rPCA) is then performed on these wavelet
      coefficients to obtain features in a lower dimension. The rPCA based features are
      used for constructing a self-organizing map (SOM). Finally, hierarchical
      clustering is applied on the SOM that separates anomalous signals residing in the
      smaller clusters and breaks them into logical units for contamination
      identification. The proposed methodology is tested using synthetic and real world
      EMG signals. The synthetic EMG signals are generated using a heteroscedastic
      process mimicking desired experimental setups. A sub-part of these synthetic
      signals is introduced with anomalies. These results are followed with real EMG
      signals introduced with synthetic anomalies. Finally, a heterogeneous real world
      data set is used with known quality issues under an unsupervised setting. The
      framework provides recall of 90% (+/- 3.3) and precision of 99%(+/-0.4).

PMID- 29641382
TI  - Motor Skill Development Alters Kinematics and Co-Activation Between Flexors and
      Extensors of Limbs in Human Infant Crawling.
AB  - Hands and knees crawling is an important motor developmental milestone but the
      current clinical measures of motor function during crawling stage are relatively
      subjective. Objective metrics using kinematics and electromyography (EMG) in
      infant crawling may provide more stable and accurate measures of such
      developmental milestone, demonstrating changes in locomotion during age span. The
      purpose of this paper was to determine whether joint kinematics and the
      underlying co-activation between flexor and extensor in infant crawling are
      different for arms and legs across the infant age span. Surface EMG of two pairs
      of flexors and extensors from arms and legs and the corresponding joint kinematic
      data were collected in twenty health infants (11 males and 9 females, range 8-15
      months), while they were crawling on hands and knees. Co-activation index of
      averaged EMG was used to quantify the simultaneous contractions between flexor
      and extensor muscles. Coefficient of variation of joint's maximum vertical
      acceleration from multiple cycles was used to quantify the repeatability of
      kinematics during crawling. Our results indicated that the arm exhibited
      significantly higher co-activation and higher repeatability of joint movement
      than the leg, suggesting earlier development of arm compared to leg. Moreover,
      elder age groups, who had stronger walking ability developed, showed increased co
      activation of the leg and significant increase in repeatability of the knee
      movement. These results were consistent with the rapid reinforcement of the leg
      during motor development from quadrupeds to bipedal walking. Furthermore, the EMG
      and kinematic parameters were significantly correlated with clinical variables.
      These results suggest that the EMG and kinematic analysis of infant crawling are
      useful in building effective assessment of infant's motor function before
      independent walking.

PMID- 29641383
TI  - A Unified Controller for Walking on Even and Uneven Terrain With a Powered Ankle
      Prosthesis.
AB  - This paper describes the development of a controller for a powered ankle
      prosthesis that is intended to provide appropriate biomechanical behavior for
      walking on both even and uneven terrain without having to explicitly detect local
      slope to do so. In order to inform development of the controller, the authors
      conducted a small study of five healthy subjects walking on even and uneven
      terrain. Data from the healthy subject study were used to formulate behavioral
      models for the healthy ankle, which were then implemented as controller behaviors
      in the powered prosthesis prototype and comparatively assessed on an amputee
      subject.

PMID- 29641384
TI  - Usability and Validation of the Smarter Balance System: An Unsupervised Dynamic
      Balance Exercises System for Individuals With Parkinson's Disease.
AB  - Conventional physical and balance rehabilitation programs to improve balance
      performance and increase postural stability are often limited due to cost,
      availability of physical therapists, and accessibility to rehabilitation
      facilities. Exercise compliance is also affected by a loss of memory and decline
      in motivation in prescribed home-based balance training. We have developed the
      smarter balance system (SBS) incorporating multimodal biofeedback (visual plus
      vibrotactile) intended for clinical and home-based balance rehabilitation and
      assessed its efficacy on physical therapists' recommended dynamic weight-shifting
      balance exercises (dynamic WSBE) in individuals with Parkinson's disease (PD).
      The SBS consists of a smartphone and custom belt housing a processing unit,
      miniaturized sensors, and vibrating actuators (tactors). Visual and vibrotactile
      biofeedback guidance during dynamic WSBE is generated by the SBS's custom app
      based on 90% of the user's limits of stability (LOS). Ten individuals with
      idiopathic PD having impaired postural stability participated in one unsupervised
      session comprising 24 trials of the dynamic WSBE in a laboratory setting.
      Participants' limits of stability (LOS) in the anterior-posterior (A/P) and
      medial-lateral (M/L) direction were measured at the pre- and post-session. To
      assess the efficacy of SBS to provide guidance during balance rehabilitation
      using dynamic WSBE, cross-correlation (XCOR), position error (PE), and percent of
      tactor activation (PTA) were measured. There was a significant increase in LOS
      between the pre- and post-training session in both A/P and M/L directions. The
      average XCOR across all participants were 0.87 (SD = 0.11) and 0.76 (SD = 0.11)
      for the A/P and M/L direction respectively. The average PE and PTA for the A/P
      direction was 1.17 deg (SD = 0.60) and 65.35% (SD = 15.1) respectively and 0.74
      deg (SD = 0.28) and 31.3% (SD = 16.42) in the M/L direction respectively. There
      was no significant effect of trials for XCOR, PE, and PTA. Participants' LOS
      significantly increased after one session of the dynamic WSBE. Individuals with
      PD could accurately follow the target movements during the dynamic WSBE using the
      SBS. Future studies will assess the efficacy and acceptability of the SBS during
      long-term in-home rehabilitative training for balance-impaired individuals.

PMID- 29641385
TI  - EMG-Torque Dynamics Change With Contraction Bandwidth.
AB  - An accurate model for ElectroMyoGram (EMG)-torque dynamics has many uses. One of
      its applications which has gained high attention among researchers is its use, in
      estimating the muscle contraction level for the efficient control of prosthesis.
      In this paper, the dynamic relationship between the surface EMG and torque during
      isometric contractions at the human ankle was studied using system identification
      techniques. Subjects voluntarily modulated their ankle torque in dorsiflexion
      direction, by activating their tibialis anterior muscle, while tracking a pseudo
      random binary sequence in a torque matching task. The effects of contraction
      bandwidth, described by torque spectrum, on EMG-torque dynamics were evaluated by
      varying the visual command switching time. Nonparametric impulse response
      functions (IRF) were estimated between the processed surface EMG and torque. It
      was demonstrated that: 1) at low contraction bandwidths, the identified IRFs had
      unphysiological anticipatory (i.e., non-causal) components, whose amplitude
      decreased as the contraction bandwidth increased. We hypothesized that this non
      causal behavior arose, because the EMG input contained a component due to
      feedback from the output torque, i.e., it was recorded from within a closed-loop.
      Vision was not the feedback source since the non-causal behavior persisted when
      visual feedback was removed. Repeating the identification using a nonparametric
      closed-loop identification algorithm yielded causal IRFs at all bandwidths,
      supporting this hypothesis. 2) EMG-torque dynamics became faster and the
      bandwidth of system increased as contraction modulation rate increased. Thus,
      accurate prediction of torque from EMG signals must take into account the
      contraction bandwidth sensitivity of this system.

PMID- 29641386
TI  - Differential Inverse Kinematics of a Redundant 4R Exoskeleton Shoulder Joint.
AB  - Most active upper-extremity rehabilitation exoskeleton designs incorporate a
      three sequential rotational shoulder joint with orthogonal axes. This kind of
      joint has poor conditioning close to singular configurations when all joint axes
      become coplanar, which reduces its effective range of motion. We investigate an
      alternative approach of using a redundant non-orthogonal 4R shoulder joint. By
      inspecting the behavior of the possible nullspace motions, a new method is
      devised to resolve the redundancy in the differential inverse kinematics (IK)
      problem. A 1D nullspace global attraction method is used, instead of naive
      nullspace projection, to guarantee proper convergence. The design of the
      exoskeleton and the proposed IK method ensure good conditioning, avoid collisions
      with the human head, arm and trunk, can reach the entire human workspace, and
      outperforms conventional 3R orthogonal exoskeleton designs in terms of lower
      joint velocities and no body collisions.

PMID- 29641387
TI  - An Optimal Method of Training the Specific Lower Limb Muscle Group Using an
      Exoskeletal Robot.
AB  - This paper suggests a novel method of strengthening specific muscle groups in the
      lower limb during a functional movement. When the foot of an user wearing an
      exoskeletal robot follows a given path, the contribution of each muscle group to
      generate the motion changes along the path of the trajectory. The efficiency of
      muscle training, which is defined as the ratio of the work of a specific muscle
      group to that of all groups, can be maximized by changing the training load along
      the path. Based on a musculoskeletal model, the contribution of each muscle group
      along the path can be calculated as a function of its position. When a specific
      muscle group is chosen for exercise or rehabilitation, the efficiency of training
      can be maximized by setting high load where its contribution is high and low load
      where its contribution is low. By doing so, the user can exercise longer with the
      same amount of energy consumption. The EXOWheel that features a lower limb
      exoskeleton is employed to verify the method and the hamstring muscle group is
      selected as the specific muscle group. Three healthy subjects participate in the
      experiment, and electromyogram sensors are employed to monitor the muscle power.
      The results indicate that the efficiency of the hamstring muscle group for a
      given circular foot path under the optimal training load is 46.2% compared with
      32.5% with a constant load and it means the 42% higher efficiency of the specific
      muscle group training.

PMID- 29641388
TI  - Focal Vibration Stretches Muscle Fibers by Producing Muscle Waves.
AB  - Focal vibration is an effective intervention for the management of spasticity.
      However, its neuromechanical effects, particularly how tonic vibration reflex is
      induced explicitly, remain implicit. In this paper, we utilize a high-speed
      camera and a method of image processing to quantify the muscle vibration
      rigorously and disclose the neuromechanical mechanism of focal vibration. The
      vibration of 75 Hz is applied on the muscle belly of the biceps brachii and
      muscle responses are captured by a high-speed camera in profile. The muscle
      silhouettes are identified by the Canny edge detector to represent the stretch of
      muscle fibers, and the consistency between the muscle stretch and profile
      deformation has been confirmed by the magnetic resonance imaging in advance.
      Oscillations of muscle points discretized by pixels are identified by the fast
      Fourier transformation, respectively, and results demonstrate that focal
      vibration stretches muscle by producing muscle waves. Specifically, each point
      vibrates harmonically, and, given the linear phase modulation with transverse
      position, the muscle vibration propagates as traveling waves. The propagation of
      muscle waves is associated with muscle stretch, whose frequency is the same with
      the vibrator due to the curved baseline, and thus induces the tonic vibration
      reflex via spinal circuits.

PMID- 29641389
TI  - Retraining of Human Gait - Are Lightweight Cable-Driven Leg Exoskeleton Designs
      Effective?
AB  - Exoskeletons for gait training commonly use a rigid-linked "skeleton" which makes
      them heavy and bulky. Cable-driven exoskeletons eliminate the rigid-linked
      skeleton, providing a lighter and transparent design. Current cable-driven
      exoskeletons are aimed only at gait assistance by providing short bursts of
      forces to the leg during walking. It has not yet been shown if these designs are
      suitable for gait retraining, where rehabilitative forces need to be continuously
      applied to the leg in response to errors from a desired movement. The goal of
      this study is to investigate if a cable-driven leg exoskeleton can retrain the
      gait of human users. Nine healthy subjects were trained by a cable-driven leg
      exoskeleton to walk in a new gait pattern with 30% increase in step height from
      their natural gait. After 40 min of training, the gait of the subjects became
      significantly closer to the target gait than before the training. In three
      different post-training sessions, the step height of the subjects increased by
      22%, 29%, and 31% on an average. In a fourth post-training session, when the
      subjects were instructed to ignore the training and walk naturally, the step
      height remained increased by 11%. These results confirm the potential of cable
      driven designs in gait training applications.

PMID- 29641390
TI  - Simultaneous Recognition and Assessment of Post-Stroke Hemiparetic Gait by Fusing
      Kinematic, Kinetic, and Electrophysiological Data.
AB  - Gait analysis for the patients with lower limb motor dysfunction is a useful tool
      in assisting clinicians for diagnosis, assessment, and rehabilitation strategy
      making. Implementing accurate automatic gait analysis for the hemiparetic
      patients after stroke is a great challenge in clinical practice. This study is to
      develop a new automatic gait analysis system for qualitatively recognizing and
      quantitatively assessing the gait abnormality of the post-stroke hemiparetic
      patients. Twenty-one post-stroke patients and twenty-one healthy volunteers
      participated in the walking trials. Three of the most representative gait data,
      i.e., marker trajectory (MT), ground reaction force (GRF), and electromyogram,
      were simultaneously acquired from these subjects during their walking. A
      multimodal fusion architecture is established by using these different modal data
      to qualitatively distinguish the hemiparetic gait from normal gait by different
      pattern recognition techniques and to quantitatively estimate the patient's lower
      limb motor function by a novel probability-based gait score. Seven decision
      fusion algorithms have been tested in this architecture, and extensive data
      analysis experiments have been conducted. The results indicate that the
      recognition performance and estimation performance of the system become better
      when more modal gait data are fused. For the recognition performance, the random
      forest classifier based on the GRF data achieves an accuracy of 92.26%
      outperformed other single-modal schemes. When combining two modal data, the
      accuracy can be enhanced to 95.83% by using the support vector machine (SVM)
      fusion algorithm to fuse the MT and GRF data. When integrating all the three
      modal data, the accuracy can be further improved to 98.21% by using the SVM
      fusion algorithm. For the estimation performance, the absolute values of the
      correlation coefficients between the estimation results of the above three
      schemes and the Wisconsin gait scale scores for the post-stroke patients are
      0.63, 0.75, and 0.84, respectively, which means the clinical relevance becomes
      more obvious when using more modalities. These promising results demonstrate that
      the proposed method has considerable potential to promote the future design of
      automatic gait analysis systems for clinical practice.

PMID- 29641391
TI  - Synthesis of Subject-Specific Human Balance Responses Using a Task-Level
      Neuromuscular Control Platform.
AB  - Many activities of daily living require a high level of neuromuscular
      coordination and balance control to avoid falls. Complex musculoskeletal models
      paired with detailed neuromuscular simulations complement experimental studies
      and uncover principles of coordinated and uncoordinated movements. Here, we
      created a closed-loop forward dynamic simulation framework that utilizes a
      detailed musculoskeletal model (19 degrees of freedom, and 92 muscles) to
      synthesize human balance responses after support-surface perturbation. In
      addition, surrogate response models of task-level experimental kinematics from
      two healthy subjects were provided as inputs to our closed-loop simulations to
      inform the design of the task-level controller. The predicted muscle activations
      and the resulting synthesized subject joint angles showed good conformity with
      the average of experimental trials. The simulated whole-body center of mass
      displacements, generated from a single kinematics trial per perturbation
      direction, were on average, within 7 mm (anterior perturbations) and 13 mm
      (posterior perturbations) of experimental displacements. Our results confirmed
      how a complex subject-specific movement can be reconstructed by sequencing and
      prioritizing multiple task-level commands to achieve desired movements. By
      combining the multidisciplinary approaches of robotics and biomechanics, the
      platform demonstrated here offers great potential for studying human movement
      control and subject-specific outcome prediction.

PMID- 29641392
TI  - A Noninvasive Brain-Computer Interface for Real-Time Speech Synthesis: The
      Importance of Multimodal Feedback.
AB  - We conducted a study of a motor imagery brain-computer interface (BCI) using
      electroencephalography to continuously control a formant frequency speech
      synthesizer with instantaneous auditory and visual feedback. Over a three-session
      training period, sixteen participants learned to control the BCI for production
      of three vowel sounds (/ textipa i/ [heed], / textipa A/ [hot], and / textipa u/
      [who'd]) and were split into three groups: those receiving unimodal auditory
      feedback of synthesized speech, those receiving unimodal visual feedback of
      formant frequencies, and those receiving multimodal, audio-visual (AV) feedback.
      Audio feedback was provided by a formant frequency artificial speech synthesizer,
      and visual feedback was given as a 2-D cursor on a graphical representation of
      the plane defined by the first two formant frequencies. We found that combined AV
      feedback led to the greatest performance in terms of percent accuracy, distance
      to target, and movement time to target compared with either unimodal feedback of
      auditory or visual information. These results indicate that performance is
      enhanced when multimodal feedback is meaningful for the BCI task goals, rather
      than as a generic biofeedback signal of BCI progress.

PMID- 29641393
TI  - How are Muscle Synergies Affected by Electromyography Pre-Processing?
AB  - Muscle synergies have been used for decades to explain a variety of motor
      behaviors, both in humans and animals and, more recently, to steer rehabilitation
      strategies. However, many sources of variability such as factorization
      algorithms, criteria for dimensionality reduction and data pre-processing
      constitute a major obstacle to the successful comparison of the results obtained
      by different research groups. Starting from the canonical EMG processing we
      determined how variations in filter cut-off frequencies and normalization
      methods, commonly found in literature, affect synergy weights and inter-subject
      similarity (ISS) using experimental data related to a 15-muscles upper-limb
      reaching task. Synergy weights were not significantly altered by either
      normalization (maximum voluntary contraction - MVC - or maximum amplitude of the
      signal - SELF) or band-pass filter ([20-500 Hz] or [50-500] Hz). Normalization
      did, however, alter the amount of variance explained by a set of synergies, which
      is a criterion often used for model order selection. Comparing different low-pass
      (LP) filters (0.5 Hz, 4 Hz, 10 Hz, 20 Hz cut-offs) we showed that increasing the
      low pass filter cut-off had the effect of decreasing the variance accounted for
      by a set number of synergies and affected individual muscle contributions.
      Extreme smoothing (i.e., LP cut-off 0.5 Hz) enhanced the contrast between active
      and inactive muscles but had an unpredictable effect on the ISS. The results
      presented here constitute a further step towards a thoughtful EMG pre-processing
      for the extraction of muscle synergies.

PMID- 29641394
TI  - Voluntary Control of Residual Antagonistic Muscles in Transtibial Amputees:
      Feedforward Ballistic Contractions and Implications for Direct Neural Control of
      Powered Lower Limb Prostheses.
AB  - Discrete, rapid (i.e., ballistic like) muscle activation patterns have been
      observed in ankle muscles (i.e., plantar flexors and dorsiflexors) of able-bodied
      individuals during voluntary posture control. This observation motivated us to
      investigate whether transtibial amputees are capable of generating such a
      ballistic-like activation pattern accurately using their residual ankle muscles
      in order to assess whether the volitional postural control of a powered ankle
      prosthesis using proportional myoelectric control via residual muscles could be
      feasible. In this paper, we asked ten transtibial amputees to generate ballistic
      like activation patterns using their residual lateral gastrocnemius and residual
      tibialis anterior to control a computer cursor via proportional myoelectric
      control to hit targets positioned at 20% and 40% of maximum voluntary contraction
      of the corresponding residual muscle. During practice conditions, we asked
      amputees to hit a single target repeatedly. During testing conditions, we asked
      amputees to hit a random sequence of targets. We compared movement time to target
      and end-point accuracy. We also examined motor recruitment synchronization via
      time-frequency representations of residual muscle activation. The result showed
      that median end-point error ranged from -0.6% to 1% maximum voluntary contraction
      across subjects during practice, which was significantly lower compared to
      testing ( ). Average movement time for all amputees was 242 ms during practice
      and 272 ms during testing. Motor recruitment synchronization varied across
      subjects, and amputees with the highest synchronization achieved the fastest
      movement times. End-point accuracy was independent of movement time. Results
      suggest that it is feasible for transtibial amputees to generate ballistic
      control signals using their residual muscles. Future work on volitional control
      of powered power ankle prostheses might consider anticipatory postural control
      based on ballistic-like residual muscle activation patterns and direct continuous
      proportional myoelectric control.

PMID- 29641395
TI  - Influence of Elbow Flexion and Stimulation Site on Neuromuscular Electrical
      Stimulation of the Biceps Brachii.
AB  - Functional electrical stimulation (FES) can help individuals with physical
      disabilities by assisting limb movement; however, the change in muscle geometry
      associated with limb movement may affect the response to stimulation. The aim of
      this paper was to quantify the effects of elbow flexion and stimulation site on
      muscle torque production. Contraction torque about the elbow was measured in 12
      healthy individuals using a custom elbow flexion testbed and a transcutaneous
      electrode array. Stimulation was delivered to six distinct sites along the biceps
      brachii over 11 elbow flexion angles. Flexion angle was found to significantly
      influence the optimal (i.e., torque-maximizing) stimulation site ( ), with post
      hoc analysis indicating a proximal shift in optimal stimulation site with
      increased flexion. Similarly, the biceps stimulation site was found to
      significantly influence the flexion angle at which peak torque occurred ( ), with
      post hoc analysis indicating an increase in peak-torque flexion angle as
      stimulation site is moved proximally up the biceps. Since maximizing muscle force
      per unit stimulation is a common goal in rehabilitative FES, future efforts could
      examine methods which compensate for the shift in optimal stimulation site during
      FES-induced limb movement.

PMID- 29641396
TI  - Toward Optimization of Gaze-Controlled Human-Computer Interaction: Application to
      Hindi Virtual Keyboard for Stroke Patients.
AB  - Virtual keyboard applications and alternative communication devices provide new
      means of communication to assist disabled people. To date, virtual keyboard
      optimization schemes based on script-specific information, along with multimodal
      input access facility, are limited. In this paper, we propose a novel method for
      optimizing the position of the displayed items for gaze-controlled tree-based
      menu selection systems by considering a combination of letter frequency and
      command selection time. The optimized graphical user interface layout has been
      designed for a Hindi language virtual keyboard based on a menu wherein 10
      commands provide access to type 88 different characters, along with additional
      text editing commands. The system can be controlled in two different modes: eye
      tracking alone and eye-tracking with an access soft-switch. Five different
      keyboard layouts have been presented and evaluated with ten healthy participants.
      Furthermore, the two best performing keyboard layouts have been evaluated with
      eye-tracking alone on ten stroke patients. The overall performance analysis
      demonstrated significantly superior typing performance, high usability (87% SUS
      score), and low workload (NASA TLX with 17 scores) for the letter frequency and
      time-based organization with script specific arrangement design. This paper
      represents the first optimized gaze-controlled Hindi virtual keyboard, which can
      be extended to other languages.

PMID- 29641397
TI  - Adaptive Residual Networks for High-Quality Image Restoration.
AB  - Image restoration methods based on convolutional neural networks have shown great
      success in the literature. However, since most of networks are not deep enough,
      there is still some room for the performance improvement. On the other hand,
      though some models are deep and introduce shortcuts for easy training, they
      ignore the importance of location and scaling of different inputs within the
      shortcuts. As a result, existing networks can only handle one specific image
      restoration application. To address such problems, we propose a novel adaptive
      residual network (ARN) for high-quality image restoration in this paper. Our ARN
      is a deep residual network, which is composed of convolutional layers, parametric
      rectified linear unit layers, and some adaptive shortcuts. We assign different
      scaling parameters to different inputs of the shortcuts, where the scaling is
      considered as part parameters of the ARN and trained adaptively according to
      different applications. Due to the special construction of ARN, it can solve many
      image restoration problems and have superior performance. We demonstrate its
      capabilities with three representative applications, including Gaussian image
      denoising, single image super resolution, and JPEG image deblocking. Experimental
      results prove that our model greatly outperforms numerous state-of-the-art
      restoration methods in terms of both peak signal-to-noise ratio and structure
      similarity index metrics, e.g., it achieves 0.2-0.3 dB gain in average compared
      with the second best method at a wide range of situations.

PMID- 29641398
TI  - Visual Navigation Using Projection of Spatial Right-Angle In Indoor Environment.
AB  - Helping robots understand indoor scenes has considerable value in computer
      vision. However, due to the diversity of indoor scenes, understanding them
      remains a big challenge. There are many spatial right-angles in indoor scenes.
      These spatial right-angles are projected into diverse 2D projections. These
      projections can be considered a composition of a pair of lines (line-pairs).
      Given the vanishing points (VPs), line segments can be assigned to 1 of 3 main
      orthogonal directions. The line-pairs (intersection of 2 lines), such that each
      of them converges to a different VP, are likely to be the projection of a spatial
      right-angle onto the image plane. These projections may enable us to estimate
      their original orientation and position in 3D scenes. In this paper, we presented
      a method to efficiently understand indoor scenes from a single image, without
      training or any knowledge of the camera's internal calibration. Through geometric
      inference of line-pairs, it is possible to find these spatial right-angle
      projections. Then, these projections can be assigned to different clusters, and
      the line that lies in the neighbor-cluster helps us estimate the layout of the
      indoor scene. The proposed approach required no prior training. We compared the
      room layout estimated by our algorithm against the room box ground truth,
      measuring the percentage of pixels that were correctly classified. These
      experiments showed that our method estimated not only room layout, but also
      details of the indoor scene.

PMID- 29641399
TI  - Learning-Based Just-Noticeable-Quantization- Distortion Modeling for Perceptual
      Video Coding.
AB  - Conventional predictive video coding-based approaches are reaching the limit of
      their potential coding efficiency improvements, because of severely increasing
      computation complexity. As an alternative approach, perceptual video coding (PVC)
      has attempted to achieve high coding efficiency by eliminating perceptual
      redundancy, using just-noticeable-distortion (JND) directed PVC. The previous
      JNDs were modeled by adding white Gaussian noise or specific signal patterns into
      the original images, which were not appropriate in finding JND thresholds due to
      distortion with energy reduction. In this paper, we present a novel discrete
      cosine transform-based energy-reduced JND model, called ERJND, that is more
      suitable for JND-based PVC schemes. Then, the proposed ERJND model is extended to
      two learning-based just-noticeable-quantization-distortion (JNQD) models as
      preprocessing that can be applied for perceptual video coding. The two JNQD
      models can automatically adjust JND levels based on given quantization step
      sizes. One of the two JNQD models, called LR-JNQD, is based on linear regression
      and determines the model parameter for JNQD based on extracted handcraft
      features. The other JNQD model is based on a convolution neural network (CNN),
      called CNN-JNQD. To our best knowledge, our paper is the first approach to
      automatically adjust JND levels according to quantization step sizes for
      preprocessing the input to video encoders. In experiments, both the LR-JNQD and
      CNN-JNQD models were applied to high efficiency video coding (HEVC) and yielded
      maximum (average) bitrate reductions of 38.51% (10.38%) and 67.88% (24.91%),
      respectively, with little subjective video quality degradation, compared with the
      input without preprocessing applied.

PMID- 29641400
TI  - Towards a Closed Form Second-Order Natural Scene Statistics Model.
AB  - Previous work on natural scene statistics (NSS)-based image models has focused
      primarily on characterizing the univariate bandpass statistics of single pixels.
      These models have proven to be powerful tools driving a variety of computer
      vision and image/video processing applications, including depth estimation, image
      quality assessment, and image denoising, among others. Multivariate NSS models
      descriptive of the joint distributions of spatially separated bandpass image
      samples have, however, received relatively little attention. Here, we develop a
      closed form bivariate spatial correlation model of bandpass and normalized image
      samples that completes an existing 2D joint generalized Gaussian distribution
      model of adjacent bandpass pixels. Our model is built using a set of diverse,
      high-quality naturalistic photographs, and as a control, we study the model
      properties on white noise. We also study the way the model fits are affected when
      the images are modified by common distortions.

PMID- 29641401
TI  - Self-Supervised Video Hashing With Hierarchical Binary Auto-Encoder.
AB  - Existing video hash functions are built on three isolated stages: frame pooling,
      relaxed learning, and binarization, which have not adequately explored the
      temporal order of video frames in a joint binary optimization model, resulting in
      severe information loss. In this paper, we propose a novel unsupervised video
      hashing framework dubbed self-supervised video hashing (SSVH), which is able to
      capture the temporal nature of videos in an end-to-end learning to hash fashion.
      We specifically address two central problems: 1) how to design an encoder-decoder
      architecture to generate binary codes for videos and 2) how to equip the binary
      codes with the ability of accurate video retrieval. We design a hierarchical
      binary auto-encoder to model the temporal dependencies in videos with multiple
      granularities, and embed the videos into binary codes with less computations than
      the stacked architecture. Then, we encourage the binary codes to simultaneously
      reconstruct the visual content and neighborhood structure of the videos.
      Experiments on two real-world data sets show that our SSVH method can
      significantly outperform the state-of-the-art methods and achieve the current
      best performance on the task of unsupervised video retrieval.

PMID- 29641402
TI  - Prior-Based Quantization Bin Matching for Cloud Storage of JPEG Images.
AB  - Millions of user-generated images are uploaded to social media sites like
      Facebook daily, which translate to a large storage cost. However, there exists an
      asymmetry in upload and download data: only a fraction of the uploaded images are
      subsequently retrieved for viewing. In this paper, we propose a cloud storage
      system that reduces the storage cost of all uploaded JPEG photos, at the expense
      of a controlled increase in computation mainly during download of requested image
      subset. Specifically, the system first selectively re-encodes code blocks of
      uploaded JPEG images using coarser quantization parameters for smaller storage
      sizes. Then during download, the system exploits known signal priors-sparsity
      prior and graph-signal smoothness prior-for reverse mapping to recover original
      fine quantization bin indices, with either deterministic guarantee (lossless
      mode) or statistical guarantee (near-lossless mode). For fast reverse mapping, we
      use small dictionaries and sparse graphs that are tailored for specific clusters
      of similar blocks, which are classified via tree-structured vector quantizer.
      During image upload, cluster indices identifying the appropriate dictionaries and
      graphs for the re-quantized blocks are encoded as side information using a
      differential distributed source coding scheme to facilitate reverse mapping
      during image download. Experimental results show that our system can reap
      significant storage savings (up to 12.05%) at roughly the same image PSNR (within
      0.18 dB).

PMID- 29641403
TI  - Fully Connected Network-Based Intra Prediction for Image Coding.
AB  - This paper proposes a deep learning method for intra prediction. Different from
      traditional methods utilizing some fixed rules, we propose using a fully
      connected network to learn an end-to-end mapping from neighboring reconstructed
      pixels to the current block. In the proposed method, the network is fed by
      multiple reference lines. Compared with traditional single line-based methods,
      more contextual information of the current block is utilized. For this reason,
      the proposed network has the potential to generate better prediction. In
      addition, the proposed network has good generalization ability on different
      bitrate settings. The model trained from a specified bitrate setting also works
      well on other bitrate settings. Experimental results demonstrate the
      effectiveness of the proposed method. When compared with high efficiency video
      coding reference software HM-16.9, our network can achieve an average of 3.4%
      bitrate saving. In particular, the average result of 4K sequences is 4.5% bitrate
      saving, where the maximum one is 7.4%.

PMID- 29641404
TI  - Manifold-Based Visual Object Counting.
AB  - Visual object counting (VOC) is an emerging area in computer vision which aims to
      estimate the number of objects of interest in a given image or video. Recently,
      object density based estimation method is shown to be promising for object
      counting as well as rough instance localization. However, the performance of this
      method tends to degrade when dealing with new objects and scenes. To address this
      limitation, we propose a manifold-based method for visual object counting (M
      VOC), based on the manifold assumption that similar image patches share similar
      object densities. Firstly, the local geometry of a given image patch is
      represented linearly by its neighbors using a predefined patch training set, and
      the object density of this given image patch is reconstructed by preserving the
      local geometry using locally linear embedding. To improve the characterization of
      local geometry, additional constraints such as sparsity and non-negativity are
      also considered via regularization, nonlinear mapping, and kernel trick. Compared
      with the state-of-the-art VOC methods, our proposed M-VOC methods achieve
      competitive performance on seven benchmark datasets. Experiments verify that the
      proposed M-VOC methods have several favorable properties, such as robustness to
      the variation in the size of training dataset and image resolution, as often
      encountered in real-world VOC applications.

PMID- 29641405
TI  - A Deep Spatial Contextual Long-Term Recurrent Convolutional Network for Saliency
      Detection.
AB  - Traditional saliency models usually adopt hand-crafted image features and human
      designed mechanisms to calculate local or global contrast. In this paper, we
      propose a novel computational saliency model, i.e., deep spatial contextual long
      term recurrent convolutional network (DSCLRCN), to predict where people look in
      natural scenes. DSCLRCN first automatically learns saliency related local
      features on each image location in parallel. Then, in contrast with most other
      deep network based saliency models which infer saliency in local contexts,
      DSCLRCN can mimic the cortical lateral inhibition mechanisms in human visual
      system to incorporate global contexts to assess the saliency of each image
      location by leveraging the deep spatial long short-term memory (DSLSTM) model.
      Moreover, we also integrate scene context modulation in DSLSTM for saliency
      inference, leading to a novel deep spatial contextual LSTM (DSCLSTM) model. The
      whole network can be trained end-to-end and works efficiently when testing.
      Experimental results on two benchmark datasets show that DSCLRCN can achieve
      state-of-the-art performance on saliency detection. Furthermore, the proposed
      DSCLSTM model can significantly boost the saliency detection performance by
      incorporating both global spatial interconnections and scene context modulation,
      which may uncover novel inspirations for studies on them in computational
      saliency models.

PMID- 29641406
TI  - Vehicle Re-Identification by Deep Hidden Multi-View Inference.
AB  - Vehicle re-identification (re-ID) is an area that has received far less attention
      in the computer vision community than the prevalent person re-ID. Possible
      reasons for this slow progress are the lack of appropriate research data and the
      special 3D structure of a vehicle. Previous works have generally focused on some
      specific views (e.g., front); but, these methods are less effective in realistic
      scenarios, where vehicles usually appear in arbitrary views to cameras. In this
      paper, we focus on the uncertainty of vehicle viewpoint in re-ID, proposing two
      end-to-end deep architectures: the Spatially Concatenated ConvNet and
      convolutional neural network (CNN)-LSTM bi-directional loop. Our models exploit
      the great advantages of the CNN and long short-term memory (LSTM) to learn
      transformations across different viewpoints of vehicles. Thus, a multi-view
      vehicle representation containing all viewpoints' information can be inferred
      from the only one input view, and then used for learning to measure distance. To
      verify our models, we also introduce a Toy Car RE-ID data set with images from
      multiple viewpoints of 200 vehicles. We evaluate our proposed methods on the Toy
      Car RE-ID data set and the public Multi-View Car, VehicleID, and VeRi data sets.
      Experimental results illustrate that our models achieve consistent improvements
      over the state-of-the-art vehicle re-ID approaches.

PMID- 29641407
TI  - Automatic Depth Extraction from 2D Images Using a Cluster-Based Learning
      Framework.
AB  - There has been a significant increase in the availability of 3D players and
      displays in the last years. Nonetheless, the amount of 3D content has not
      experimented an increment of such magnitude. To alleviate this problem, many
      algorithms for converting images and videos from 2D to 3D have been proposed.
      Here, we present an automatic learning-based 2D-3D image conversion approach,
      based on the key hypothesis that color images with similar structure likely
      present a similar depth structure. The presented algorithm estimates the depth of
      a color query image using the prior knowledge provided by a repository of color +
      depth images. The algorithm clusters this database attending to their structural
      similarity, and then creates a representative of each color-depth image cluster
      that will be used as prior depth map. The selection of the appropriate prior
      depth map corresponding to one given color query image is accomplished by
      comparing the structural similarity in the color domain between the query image
      and the database. The comparison is based on a K-Nearest Neighbor framework that
      uses a learning procedure to build an adaptive combination of image feature
      descriptors. The best correspondences determine the cluster, and in turn the
      associated prior depth map. Finally, this prior estimation is enhanced through a
      segmentation-guided filtering that obtains the final depth map estimation. This
      approach has been tested using two publicly available databases, and compared
      with several state-of-the-art algorithms in order to prove its efficiency.

PMID- 29641408
TI  - Retinal Microaneurysms Detection Using Local Convergence Index Features.
AB  - Retinal microaneurysms (MAs) are the earliest clinical sign of diabetic
      retinopathy disease. Detection of MAs is crucial for the early diagnosis of
      diabetic retinopathy and prevention of blindness. In this paper, a novel and
      reliable method for automatic detection of MAs in retinal images is proposed. In
      the first stage of the proposed method, several preliminary microaneurysm
      candidates are extracted using a gradient weighting technique and an iterative
      thresholding approach. In the next stage, in addition to intensity and shape
      descriptors, a new set of features based on local convergence index filters is
      extracted for each candidate. Finally, the collective set of features is fed to a
      hybrid sampling/boosting classifier to discriminate the MAs from non-MAs
      candidates. The method is evaluated on images with different resolutions and
      modalities (color and scanning laser ophthalmoscope) using six publicly available
      data sets including the retinopathy online challenges (ROC) data set. The
      proposed method achieves an average sensitivity score of 0.471 on the ROC data
      set outperforming state-of-the-art approaches in an extensive comparison. The
      experimental results on the other five data sets demonstrate the effectiveness
      and robustness of the proposed MAs detection method regardless of different image
      resolutions and modalities.

PMID- 29641409
TI  - Recurrent and Dynamic Models for Predicting Streaming Video Quality of
      Experience.
AB  - Streaming video services represent a very large fraction of global bandwidth
      consumption. Due to the exploding demands of mobile video streaming services,
      coupled with limited bandwidth availability, video streams are often transmitted
      through unreliable, low-bandwidth networks. This unavoidably leads to two types
      of major streaming-related impairments: compression artifacts and/or rebuffering
      events. In streaming video applications, the end-user is a human observer; hence
      being able to predict the subjective Quality of Experience (QoE) associated with
      streamed videos could lead to the creation of perceptually optimized resource
      allocation strategies driving higher quality video streaming services. We propose
      a variety of recurrent dynamic neural networks that conduct continuous-time
      subjective QoE prediction. By formulating the problem as one of time-series
      forecasting, we train a variety of recurrent neural networks and non-linear
      autoregressive models to predict QoE using several recently developed subjective
      QoE databases. These models combine multiple, diverse neural network inputs, such
      as predicted video quality scores, rebuffering measurements, and data related to
      memory and its effects on human behavioral responses, using them to predict QoE
      on video streams impaired by both compression artifacts and rebuffering events.
      Instead of finding a single time-series prediction model, we propose and evaluate
      ways of aggregating different models into a forecasting ensemble that delivers
      improved results with reduced forecasting variance. We also deploy appropriate
      new evaluation metrics for comparing time-series predictions in streaming
      applications. Our experimental results demonstrate improved prediction
      performance that approaches human performance. An implementation of this work can
      be found at https://github.com/christosbampis/NARX_QoE_release.

PMID- 29641410
TI  - Joint Denoising/Compression of Image Contours via Shape Prior and Context Tree.
AB  - The advent of depth sensing technologies means that the extraction of object
      contours in images-a common and important pre-processing step for later higher
      level computer vision tasks like object detection and human action recognition
      has become easier. However, captured depth images contain acquisition noise and
      the detected contours suffer from errors as a result. In this paper, we propose
      to jointly denoise and compress detected contours in an image for bandwidth
      constrained transmission to a client, who can then carry out aforementioned
      application-specific tasks using the decoded contours as input. First, we prove
      theoretically that in general a joint denoising/compression approach can
      outperform a separate two-stage approach that first denoises then encodes
      contours lossily. Adopting a joint approach, we propose a burst error model that
      models typical errors encountered in an observed string of directional edges. We
      then formulate a rate-constrained maximum a posteriori problem that trades off
      the posterior probability of an estimated string given with its code rate. We
      design a dynamic programming algorithm that solves the posed problem optimally,
      and propose a compact context representation called total suffix tree that can
      reduce complexity of the algorithm dramatically. To the best of our knowledge, we
      are the first in the literature to study the problem of joint
      denoising/compression of image contours and offer a computation-efficient
      optimization algorithm. Experimental results show that our joint
      denoising/compression scheme can reduce bitrate by up to 18% compared with a
      competing separate scheme at comparable visual quality.

PMID- 29641411
TI  - SCOM: Spatiotemporal Constrained Optimization for Salient Object Detection.
AB  - This paper presents a novel model for video salient object detection called
      spatiotemporal constrained optimization model (SCOM), which exploits spatial and
      temporal cues, as well as a local constraint, to achieve a global saliency
      optimization. For a robust motion estimation of salient objects, we propose a
      novel approach to modeling the motion cues from optical flow field, the saliency
      map of the prior video frame and the motion history of change detection, which is
      able to distinguish the moving salient objects from diverse changing background
      regions. Furthermore, an effective objectness measure is proposed with intuitive
      geometrical interpretation to extract some reliable object and background
      regions, which provided as the basis to define the foreground potential,
      background potential, and the constraint to support saliency propagation. These
      potentials and the constraint are formulated into the proposed SCOM framework to
      generate an optimal saliency map for each frame in a video. The proposed model is
      extensively evaluated on the widely used challenging benchmark data sets.
      Experiments demonstrate that our proposed SCOM substantially outperforms the
      state-of-the-art saliency models.

PMID- 29641412
TI  - Insights into the activity control of the kallikrein-related peptidase 6: small
      molecule modulators and allosterism.
AB  - The activity of kallikrein-related peptidase 6 (KLK6) is deregulated in various
      diseases such as cancer and neurodegenerative diseases. KLK6 is thus considered
      as an attractive therapeutical target. In this short report, we depict some novel
      findings on the regulation of the KLK6 activity. Namely, we identified mechanism
      based inhibitors (suicide substrates) from an in-house library of 6-substituted
      coumarin-3-carboxylate derivatives. In addition, a molecular dynamics study
      evidenced the allosteric behavior of KLK6 similar to that previously observed for
      some trypsin-like serine proteases. This allosteric behavior together with the
      coumarinic scaffold bring new opportunities for the design of KLK6 potent
      activity modulators, useful as therapeutics or activity-based probes.

PMID- 29641413
TI  - Neuronal RNP granules: from physiological to pathological assemblies.
AB  - Neuronal cells rely on macro- and micro-cellular compartmentalization to rapidly
      process information, and respond locally to external stimuli. Such a cellular
      organization is achieved via the assembly of neuronal ribonucleoprotein (RNP)
      granules, dynamic membrane-less organelles enriched in RNAs and associated
      regulatory proteins. In this review, we discuss how these high-order structures
      transport mRNAs to dendrites and axons, and how they contribute to the spatio
      temporal regulation of localized mRNA translation. We also highlight how recent
      biophysical studies have shed light on the mechanisms underlying neuronal RNP
      granule dynamic assembly, remodeling and maturation, in both physiological and
      pathological contexts.

PMID- 29641414
TI  - Comparative hypoglycemic potentials and phytochemical profiles of 12 common leafy
      culinary vegetables consumed in Nsukka, Southeastern Nigeria.
AB  - Background Metabolic disease like diabetes mellitus is on the increase in
      developing countries due to lack of access to orthodox medicine owing to its high
      cost. Health benefits of culinary vegetables cannot be overemphasized. This study
      therefore aims to profile the hypoglycaemic potentials of 12 common leafy
      vegetables consumed in Nsukka, Southeastern Nigeria and advise diabetic patients
      accordingly. Methods A total of 75 albino Wistar rats assigned to 15 groups of
      five rats per group were used for the study. Diabetes was induced in groups 1-14
      rats by intraperitoneal injection of alloxan monohydrate (160 mg/kg), and rats in
      group 15 were not made diabetic. Groups 1-12 rats were treated with aqueous
      extracts of the vegetables (200 mg/kg), and group 13 rats received glibenclamide
      at 2 mg/kg and served as standard control. Rats in groups 14 and 15 received
      distilled water (10 mL/kg) to serve as negative and normal controls,
      respectively. The fasting blood glucose (FBG) values of the rats were determined
      3, 6 and 24 h post-treatment. Phytochemical studies on the vegetables were also
      carried out. Results Results revealed that the hypoglycaemic activities of
      Gongronema latifolium, Pterocarpus santalinoides, Ocimum gratissimum, Pterocarpus
      mildbraedii and Vernonia amygdalina were comparable (p>0.05) to that obtained for
      glibenclamide (standard anti-diabetic drug) while Gnetum africanum and Piper
      guineense did not show significant hypoglycaemic activities. Phytochemicals such
      as flavonoids, alkaloids, tannins, saponins, glycosides, and terpenes were
      present in the vegetables. Conclusions It was concluded that the vegetables
      possess hypoglycaemic activities at different capacities with G. latifolium being
      the most potent.

PMID- 29641416
TI  - Physical activity during pregnancy - past and present.
AB  - The possible implications of physical activity during the period of pregnancy
      have been much debated over recent decades. This brief appraisal integrates
      knowledge from an array of position papers, systematic reviews, meta-analyses,
      and recommendations provided by specialty board committees. The medical community
      is becoming more and more aware of the beneficial effects of mild and moderate
      physical activity on the mother and the fetus, including improved clinical
      correlates of subsequent vaginal delivery, as contrasted to the clearly
      unbeneficial effects of a sedentary lifestyle.

PMID- 29641415
TI  - Impact of childhood type 1 diabetes on maternal work-family relations.
AB  - BACKGROUND: The aim of the study was to evaluate work-family conflict (WFC) and
      work-family facilitation (WFF) of working mothers of children with type 1
      diabetes (T1D) compared with those of working mothers of children under follow-up
      not requiring treatment and of healthy children, and to explore the impact of
      organizational resources and the characteristics of the child and his disease on
      this interface. METHODS: The study included 157 working mothers: 50 mothers of
      children with T1D, 50 mothers of children on medical follow-up without chronic
      illness and 57 mothers of healthy children. The participants completed validated
      questionnaires including the WFC scale, WFF scale, organizational resources
      support scale, life and work satisfaction questionnaire, a background demographic
      questionnaire and a child health questionnaire. Mothers of children with T1D also
      completed a questionnaire relating to diabetes management. RESULTS: Almost half
      of the mothers of children with T1D found it necessary to reduce their working
      hours or to change their workplace. This group also reported a significantly
      higher level of colleague support. There were no significant differences in WFC
      and WFF between mothers of children with T1D and controls. CONCLUSIONS: This
      study demonstrates the effect of raising a T1D child on the mother's vocational
      behavior. Despite the additional burden, work is a source of enrichment for these
      mothers.

PMID- 29641417
TI  - [Fragile X syndrome and FMR1-dependent diseases - clinical presentation,
      epidemiology and molecular background].
AB  - Fragile X syndrome (FXS) is the second most common inherited cause of
      intellectual disability (ID), after Down syndrome. The severity of ID in FXS
      patients varies and depends mainly on the patient's sex. Besides intellectual
      disorders, additional symptoms, such as psychomotor delay, a specific behavioral
      phenotype, or emotional problems are present in FXS patients. In over 99% of the
      cases, the disease is caused by the presence of a dynamic mutation in the FMR1
      gene localized on the X chromosome. Due to the expansion of CGG nucleotides (over
      200 repeats), FMR1 gene expression is decreased and results in the significant
      reduction of the FMRP protein level. The CGG expansion to premutation range (55
      200 CGG repeats) is equivalent to the FXS carrier status and may cause FMR1
      dependent disorders - fragile X-associated primary ovarian insufficiency (FXPOI)
      and fragile X-associated tremor/ataxia syndrome (FXTAS). In contrast to FXS,
      clinical symptoms of these diseases occur later in adulthood. The aim of the
      article is to present the knowledge about the molecular background and
      epidemiology of fragile X syndrome and other FMR1-related disorders.

PMID- 29641418
TI  - [Fragile X syndrome and FMR1-dependent diseases - diagnostic scheme based on own
      experience .]
AB  - The presence of dynamic mutation in the FMR1 gene localized on the X chromosome
      (Xq28) is the major cause of Fragile X syndrome. As this syndrome is quite
      frequently diagnosed in patients with intellectual disability and autism spectrum
      disorders, the genetic testing of the FMR1 gene is a routine procedure performed
      in these patients. Molecular methods based on the PCR technique are used
      commonly, as they allow to identify normal (up to 54 CGG repeats, including grey
      zone alleles - 45-54 CGG repeats), premutation (55-200 CGG repeats) and full
      mutation (>200 CGG repeats) alleles.The article presents the basic methods used
      in the molecular diagnosis of Fragile X syndrome and other FMR1-related
      disorders. The following methods are presented: a screening test with GeneScan
      analysis, TP-PCR based tests and methods used for methylation analysis. Their
      pros and cons, as well as the resulting interpretation are discussed. Moreover,
      there is a presentation of the molecular diagnostic scheme following European
      Molecular Genetics Quality Network guidelines used in the Department of Medical
      Genetics.

PMID- 29641419
TI  - The mutation responsible for torsion dystonia type 1 shows the ability to
      stimulate intracellular aggregation of mutant huntingtin.
AB  - OBJECTIVE: Introduction: Torsion dystonia type 1 is the most common form of early
      onset primary dystonia. Previous reports have suggested that torsin 1A, a protein
      mutated in this disease, might function as a chaperone that prevents the toxic
      aggregation of misfolded polypeptides. The aim of the study: The aim of this
      study was to verify the chaperone function of torsin 1A by investigating its
      ability to prevent the aggregation of huntingtin model peptides. PATIENTS AND
      METHODS: Materials and methods: N-terminal mutant huntingtin fragments of
      different length were co-expressed in neuronal HT-22 and non-neuronal HeLa cells
      with either the wild-type or mutant (DeltaE302/303) torsin 1A protein. The
      transfected cells were immunostained and analyzed for the presence of huntingtin
      aggregates using fluorescence microscopy. RESULTS: Results: The
      immunofluorescence analysis of huntingtin subcellular distribution within the
      transfected cells showed no significant difference between the huntingtin
      aggregation levels in cells co-expressing the wild-type torsin 1A and in control
      cells co-transfected with an empty vector. Instead, it was the increased level of
      huntingtin aggregation in the presence of the torsion dystonia-causing
      DeltaE302/303 mutant that reached statistical significance in both neuronal and
      non-neuronal cells. CONCLUSION: Conclusions: Either torsin 1A does not function
      as a chaperone protein or huntingtin is not an efficient substrate for such a
      hypothetical chaperone activity. However, the ability of mutant torsin 1A to
      stimulate the accumulation of aggregation-prone polypeptides might constitute an
      important source of DeltaE302/303 pathogenicity and thus a potential target for
      future therapy.

PMID- 29641420
TI  - Neuroimaging results, short-term assessment of psychomotor development and the
      risk of autism spectrum disorder in extremely premature infants (<=28 GA) - a
      prospective cohort study (preliminary report).
AB  - OBJECTIVE: Infants <=28 GA are at particular risk of psychomotor and neurological
      developmental disorder. They also remain at a higher risk of developing autism
      spectrum disorder (ASD), characterized by persistent deficits in
      communication/social interactions and restricted, repetitive behaviors,
      activities and interests. Monitoring their development by a team of specialists
      (a neurologist, psychologist, psychiatrist) allows us to make an early diagnosis
      and to implement appropriate therapy. Neuroimaging studies during the neonatal
      period may be helpful in clarifying diagnosis and prognosis. Objective: The aim
      of the study was to search for the interrelation between the results of
      neuroimaging and the neurological, psychological and psychiatric evaluation at
      the age of 2. PATIENTS AND METHODS: Material and methods: Neonates born at <=28
      weeks between 01.06.2013 and 31.12.2015 and hospitalized at NICU were enrolled.
      We present the results of the first 12 children who have attained 2 years of
      corrected age and have undergone both neuroimaging, and neurological,
      psychological and psychiatric assessments. Transfontanel ultrasound was performed
      according to general standards, MRI between 38 and 42 weeks of corrected age.
      Neurological examination based on the Denver scale, ASD screening with use of the
      STAT test and psychological DSR assessment were performed at 2 years of corrected
      age. RESULTS: Results: Median GA was 26 weeks and median weight 795 g. The
      ultrasound examination was normal in 9 cases (75%) and MRI in 4 (33%).
      Abnormalities in the cerebellum were the main additional information found in MRI
      as compared to US. Neurological examination was normal in 8 infants (67#37;), in
      4 of whom neuroimaging was normal. In 4 (33%) infants the neurological
      examination was abnormal. Psychomotor development at an average level or above
      was found in seven (58#37;) children. In 4 of them neuroimaging was normal,
      whereas 3 had ventricular dilatation and haemorrhagic infarct. There were no
      abnormalities within the cerebellum in this group. In the remaining 5 children
      (42#37;) psychomotor development was rated as delayed. All of them had cerebellar
      haemorrhage. An increased risk of ASD was observed in 4 children who developed
      cerebellar hemorrhage. CONCLUSION: Conclusions: 1. The use of MRI at a term
      equivalent age may contribute to the prognosis of neurodevelopmental outcomes in
      extremely premature infants, allowing risk stratification and thus enhancing
      early monitoring of a child's development and functional status 2. There is a
      clear tendency towards abnormal psychomotor development and positive screening
      for ASD to co-occur with abnormal MRI findings in the cerebellum.

PMID- 29641421
TI  - [Congenital Cytomegalovirus infection - still a relevant problem (based on own
      experience and literature)].
AB  - As far as infectious factors are concerned, Cytomegalovirus is considered one of
      the most common causes of progressive hearing impairment and neurological
      disorders among children. The increasing number of CMV infections creates the
      necessity of quick diagnosis and treatment that may reduce the consequences or
      even completely resolve the condition. It is essential that the diagnostic team
      consists of not only neonatologists but also obstetricians/perinatologists. In
      many countries, including Poland, screening is not being carried out among
      pregnant women, which delays the diagnosis and the begining of antiviral
      treatment or might even indispose the therapy.

PMID- 29641422
TI  - The levels of bone alkaline phosphatase (BALP) and soluble epidermal growth
      factor receptor-2 (ECD/HER-2) in pediatric patients with osteosarcoma during
      clinical treatment.
AB  - OBJECTIVE: Aim: The aim of this study was to assess the usefulness of bone
      specific alkaline phosphatase (BALP) and the extracelluar domain of human
      epidermal growth factor receptor 2 (ECD/HER-2) measurements in pediatric patients
      with osteosarcoma as prospective prognostic and predictive markers for monitoring
      the treatment and early detection of disease recurrence. PATIENTS AND METHODS:
      Material and methods: We studied 22 patients (5 girls, 17 boys) aged 7-20 years
      with osteosarcoma (OS) treated at the Institute of Mother and Child in Warsaw.
      All the patients were evaluated for the serum levels of BALP and ECD/HER-2 before
      treatment, during pre- and postoperative chemotherapy and after the completion of
      treatment. Healthy children (n=22) were the reference group. The levels of BALP
      and ECD/HER-2 were measured using immunoenzymatic methods. RESULTS: Results: The
      values of BALP and ECD/HER-2 proteins were higher (p<0.01; p<0.05, respectively)
      in patients with osteosarcoma at the time of diagnosis compared with the control
      group. The values of both markers significantly decreased during chemotherapy in
      most patients with remission. In contrast to ECD/HER-2, the value of BALP after
      therapy was higher in patients with progression than with remission (p<0.001).
      CONCLUSION: Conclusions: Our results demonstrate the different pattern of BALP
      and ECD/HER-2 proteins during clinical treatment in patients with osteosarcoma.
      Higher values of BALP may characterize the progression of the disease and
      unfavourable prognosis. Further longitudinal studies are necessary to confirm the
      prognostic values of BALP and ECD/HER-2 proteins in this group of patients.

PMID- 29641423
TI  - Testicular necrosis secondary to incarcerated inguinal hernia in male infants.
      Own observations.
AB  - One of the possible consequences of incarcerated inguinal hernia in boys is
      testicular ischemia because of the prolonged compression of spermatic cord
      structures by the sac contents, resulting in ipsilateral testicular atrophy. This
      complication is well described in the literature and occurs in 5-34% of patients.
      The incidence of testicular atrophy secondary to incarcerated hernia is estimated
      to be 2-3%. Testicular necrosis as the result of hernia incarceration is,
      however, an extremely rare clinical setting. We present 4 male infants aged 3-10
      weeks with inguinal hernia incarceration which led to ipsilateral testicular
      loss. All the boys had to be operated on because of irreducible incarcerated
      hernia and in all the cases testicular necrosis was found intraoperatively. The
      time of incarceration before surgical intervention ranged from 4 to 12 hours
      (mean 6.75). Our data show that every case of hernia incarceration in a very
      young male infant requires rapid diagnosis and proper intervention, i.e. surgical
      treatment, instead of repeated attempts of manual reduction. Ultrasound
      examination should estimate not only blood flow through the incarcerated
      intestinal loop, but also through the ipsilateral testis. Moreover, during the
      operation of the incarcerated hernia in a boy it is necessary to estimate the
      ipsilateral testis.

PMID- 29641424
TI  - Outcome of topical steroid application in children with non-retractile prepuce.
AB  - True phimosis is overdiagnosed due to the failure to distinguish it from
      physiological phimosis, which is a normal developmental non retractability of the
      foreskin. The non-retractile prepuce in children is a cause of parental anxiety
      and concern. This leads to the majority of the children undergoing surgical
      procedures. Pathological phimosis needs to be differentiated from physiologic
      phimosis to avoid unnecessary circumcision. In recent years, topical steroid
      application use in cases of non-retractile prepuce has shown a good success rate
      and is well accepted by the parents. It has low risks, is cost effective and
      avoids anaesthetic and surgical complications. This is an observational study of
      100 children with non-retractile foreskin who were managed by local application
      of topical steroid cream (0.1% Mometasone) over a period of 6 weeks. The non
      retractibility was classified according to Kikiro's classification. These
      patients were analyzed on the basis of age at presentation, complaints at the
      first presentation, grade of phimosis at first presentation (as per Kikiro's
      classification), results of the topical steroid application as assessed at 6
      weeks after starting application and after stopping of the steroid administered
      for 6 weeks. The results were analyzed on the basis of the resolution of symptoms
      and the decrease in Kikiro's grade. Those patients in whom there was no response
      to treatment or who developed recurrence after stopping steroid treatment
      underwent circumcision. A total of 19 patients required surgical intervention in
      the form of circumcision. The use of topical steroids yields satisfactory results
      in patients with a non-retractile prepuce. It could be a first-line treatment for
      management in such cases and is an effective alternative designed to avoid
      unnecessary circumcision.

PMID- 29641425
TI  - The safety of pulmonary ultrasonography in the neonatal intensive care unit.
AB  - OBJECTIVE: Introduction: Due to specific anatomy of children are more vulnerable
      to the carcinogenic effects of ionizing radiation from chest X-rays. Lung
      ultrasound (LUS) is a validated procedure which can easily be used in diagnosing
      pathologies of the neonatal lung. However, experimental studies have shown that
      low frequency ultrasound may induce pulmonary capillary hemorrhage (PCH). Aim of
      the study: To evaluate the potential relationship between lung ultrasound and
      pulmonary hemorrhage in very low birth weight infants. PATIENTS AND METHODS:
      Patients and methods: We analysed the medical records of very low birth weight
      infants admitted to our neonatal tertiary centre between 2008 and 2011 (group 1),
      when CXR was the main procedure used to evaluate the respiratory system, and
      between 2013 and 2016 (group 2), when LUS became a routine procedure, replacing
      the chest X-ray. RESULTS: Results: 297 infants were enrolled in the first group
      and 286 in the second group, respectively. There was no difference in the
      frequency of pulmonary hemorrhages between the two groups (p=1). In the first
      group there was only one episode of PCH and in the second group no PCH was seen.
      Statistically significant differences were seen in a number of patients with
      pulmonary hemorrhage risk factors: surfactant administration (p<0.001),
      mechanical ventilation (p=0.0003), and hemodynamically significant patent ductus
      arteriosus (p=0.025). CONCLUSION: Conclusions: Routine lung ultrasound appears to
      be safe in very low birth weight infants; there were no episodes of pulmonary
      hemorrhage.

PMID- 29641426
TI  - The role of modern diagnostic imaging in diagnosing and differentiating kidney
      diseases in children.
AB  - Urinary tract diseases are in the group of the most commonly diagnosed medical
      conditions in pediatric patients. Many diseases with different etiologies are
      accompanied by pain, fever, hematuria, or urinary tract dysfunction. Those most
      common ones in children are urinary tract infections and congenital malformation.
      They can also represent tumors or changes caused by systemic diseases. Clinical
      tests and even more often additional imaging studies are required to make a
      proper diagnosis of urinary tract diseases. Just a few decades ago urography,
      cystography or voiding cystourethrography were the main methods in diagnostic
      imaging of the urinary tract. Today's imaging methods supported by digital
      radiographic and fluoroscopy systems, high sensitivity detectors with quantum
      detection, advanced algorithms eliminating motion artifacts, modern medical
      imaging monitors with a resolution of three or even eight megapixels
      significantly differ from conventional radiographic methods. The methods that are
      currently usually performed are: computed tomography, magnetic resonance imaging,
      isotopic methods and ultrasonography using elastography and new solutions in
      Doppler imaging. Modern techniques are currently focused on reducing radiation
      exposure with better imaging capabilities. The development of these techniques
      became an essential diagnostic aid in nephrological and urological practice. The
      aim of this paper is to present the latest solutions that are currently used in
      the diagnostic imaging of urinary tract diseases.

PMID- 29641427
TI  - Surgical treatment methods of urolithiasis in the pediatric population.
AB  - Urolithiasis in the pediatric population represents a major challenge associated
      with both the diagnosis and therapy of the condition. Over the past 25 years, the
      incidence has increased. The average age of pediatric patients with stones is
      about 7-8 years and the recurrence rate is 24%-50%. More than 80% of the stones
      are eliminated spontaneously. The remaining ones require conservative or surgical
      treatment. Choosing the most appropriate treatment depends on many factors.
      Surgical procedures in children are the same as in adults. These include
      extracorporeal shockwave lithotripsy (ESWL), ureterolithotripsy (URSL),
      retrograde intrarenal surgery (RIRS), percutaneous nephrolithotomy (PCNL) and
      laparoscopic or open surgery. ESWL is a method of choice for the treatment of
      stones with a diameter of <=20 mm located in the upper urinary tract, while PCNL
      is used in the treatment of deposits >=1.5 cm located in the upper pole of the
      kidney, deposits of >=1.0 cm located in the lower pole of the kidney, as well as
      hard stones such as cystic or struvite ones. URSL/RIRS is a method for ureteral
      and renal stones. Open surgery is indicated in cases when anatomical anomalies
      coexist with urolithiasis, or when the use of PCNL or ESWL is impossible. The
      ideal procedure should be effective, safe and allow the complete evacuation of
      the stones after the 1st procedure.

PMID- 29641428
TI  - ZnO-carbon nanofibers for stable, high response, and selective H2S sensors.
AB  - Hydrogen sulfide (H2S), as a typical atmospheric pollutant, is neurotoxic and
      flammable even at a very low concentration. In this study, we design stable H2S
      sensors based on ZnO-carbon nanofibers. Nanofibers with 30.34 wt% carbon are
      prepared by a facial electrospinning route followed by an annealing treatment.
      The resulting H2S sensors show excellent selectivity and response compared to the
      pure ZnO nanofiber H2S sensors, particularly the response in the range of 102-50
      ppm of H2S. Besides, they exhibited a nearly constant response of approximately
      40-20 ppm of H2S over 60 days. The superior performance of these H2S sensors can
      be attributed to the protection of carbon, which ensures the high stability of
      ZnO, and oxygen vacancies that improve the response and selectivity of H2S. The
      good performance of ZnO-carbon H2S sensors suggests that composites with oxygen
      vacancies prepared by a facial electrospinning route may provide a new research
      strategy in the field of gas sensors, photocatalysts, and semiconductor devices.

PMID- 29641430
TI  - Non-Invasive Blood Pressure Estimation from ECG Using Machine Learning
      Techniques.
AB  - BACKGROUND: Blood pressure (BP) measurements have been used widely in clinical
      and private environments. Recently, the use of ECG monitors has proliferated;
      however, they are not enabled with BP estimation. We have developed a method for
      BP estimation using only electrocardiogram (ECG) signals. METHODS: Raw ECG data
      are filtered and segmented, and, following this, a complexity analysis is
      performed for feature extraction. Then, a machine-learning method is applied,
      combining a stacking-based classification module and a regression module for
      building systolic BP (SBP), diastolic BP (DBP), and mean arterial pressure (MAP)
      predictive models. In addition, the method allows a probability distribution
      based calibration to adapt the models to a particular user. RESULTS: Using ECG
      recordings from 51 different subjects, 3129 30-s ECG segments are constructed,
      and seven features are extracted. Using a train-validation-test evaluation, the
      method achieves a mean absolute error (MAE) of 8.64 mmHg for SBP, 18.20 mmHg for
      DBP, and 13.52 mmHg for the MAP prediction. When models are calibrated, the MAE
      decreases to 7.72 mmHg for SBP, 9.45 mmHg for DBP and 8.13 mmHg for MAP.
      CONCLUSION: The experimental results indicate that, when a probability
      distribution-based calibration is used, the proposed method can achieve results
      close to those of a certified medical device for BP estimation.

PMID- 29641429
TI  - Multifaceted Role of Pneumolysin in the Pathogenesis of Myocardial Injury in
      Community-Acquired Pneumonia.
AB  - Pneumolysin (PLY), a member of the family of Gram-positive bacterial, cholesterol
      dependent, beta-barrel pore-forming cytolysins, is the major protein virulence
      factor of the dangerous respiratory pathogen, Streptococcus pneumoniae
      (pneumococcus). PLY plays a major role in the pathogenesis of community-acquired
      pneumonia (CAP), promoting colonization and invasion of the upper and lower
      respiratory tracts respectively, as well as extra-pulmonary dissemination of the
      pneumococcus. Notwithstanding its role in causing acute lung injury in severe
      CAP, PLY has also been implicated in the development of potentially fatal acute
      and delayed-onset cardiovascular events, which are now recognized as being fairly
      common complications of this condition. This review is focused firstly on
      updating mechanisms involved in the immunopathogenesis of PLY-mediated myocardial
      damage, specifically the direct cardiotoxic and immunosuppressive activities, as
      well as the indirect pro-inflammatory/pro-thrombotic activities of the toxin.
      Secondly, on PLY-targeted therapeutic strategies including, among others,
      macrolide antibiotics, natural product antagonists, cholesterol-containing
      liposomes, and fully humanized monoclonal antibodies, as well as on vaccine-based
      preventive strategies. These sections are preceded by overviews of CAP in
      general, the role of the pneumococcus as the causative pathogen, the occurrence
      and types of CAP-associated cardiac complication, and the structure and
      biological activities of PLY.

PMID- 29641432
TI  - Label-Free QCM Immunosensor for the Detection of Ochratoxin A.
AB  - Ochratoxin A (OTA) is a potent mycotoxin that poses a risk in food and feed
      moieties and subject to worldwide regulation. Laboratory-based analytical methods
      are traditionally employed for reliable OTA quantification, but these methods
      cannot provide rapid and on-site analysis, where biosensors fill this gap. In
      this study a label-free quartz crystal microbalance (QCM)-based immunosensor for
      the detection of OTA, which is one of the most important small molecule
      contaminants, was developed by direct immobilization of OTA to amine-bearing
      sensor surfaces using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)/N
      Hydroxysuccinimide (NHS) chemistry. The protein-free sensor surface enabled
      regeneration of sensor surface with 50 mM NaOH and 1% SDS up to 13 times without
      loss of performance, which would disrupt a protein-containing sensor surface. We
      developed a QCM immunosensor using the developed sensor surface with a 17.2-200
      ng/mL detection range which can be used for on-site detection of feedstuffs.

PMID- 29641431
TI  - Deoxyribonucleic Acid Damage and Repair: Capitalizing on Our Understanding of the
      Mechanisms of Maintaining Genomic Integrity for Therapeutic Purposes.
AB  - Deoxyribonucleic acid (DNA) is the self-replicating hereditary material that
      provides a blueprint which, in collaboration with environmental influences,
      produces a structural and functional phenotype. As DNA coordinates and directs
      differentiation, growth, survival, and reproduction, it is responsible for life
      and the continuation of our species. Genome integrity requires the maintenance of
      DNA stability for the correct preservation of genetic information. This is
      facilitated by accurate DNA replication and precise DNA repair. DNA damage may
      arise from a wide range of both endogenous and exogenous sources but may be
      repaired through highly specific mechanisms. The most common mechanisms include
      mismatch, base excision, nucleotide excision, and double-strand DNA (dsDNA) break
      repair. Concurrent with regulation of the cell cycle, these mechanisms are
      precisely executed to ensure full restoration of damaged DNA. Failure or
      inaccuracy in DNA repair contributes to genome instability and loss of genetic
      information which may lead to mutations resulting in disease or loss of life. A
      detailed understanding of the mechanisms of DNA damage and its repair provides
      insight into disease pathogeneses and may facilitate diagnosis and the
      development of targeted therapies.

PMID- 29641434
TI  - Advances in Multi-Sensor Information Fusion: Theory and Applications 2017.
AB  - The information fusion technique can integrate a large amount of data and
      knowledge representing the same real-world object and obtain a consistent,
      accurate, and useful representation of that object. The data may be independent
      or redundant, and can be obtained by different sensors at the same time or at
      different times. A suitable combination of investigative methods can
      substantially increase the profit of information in comparison with that from a
      single sensor. Multi-sensor information fusion has been a key issue in sensor
      research since the 1970s, and it has been applied in many fields. For example,
      manufacturing and process control industries can generate a lot of data, which
      have real, actionable business value. The fusion of these data can greatly
      improve productivity through digitization. The goal of this special issue is to
      report innovative ideas and solutions for multi-sensor information fusion in the
      emerging applications era, focusing on development, adoption, and applications.

PMID- 29641433
TI  - The Role, Involvement and Function(s) of Interleukin-35 and Interleukin-37 in
      Disease Pathogenesis.
AB  - The recently identified cytokines-interleukin (IL)-35 and interleukin (IL)-37
      have been described for their anti-inflammatory and immune-modulating actions in
      numerous inflammatory diseases, auto-immune disorders, malignancies, infectious
      diseases and sepsis. Either cytokine has been reported to be reduced and in some
      cases elevated and consequently contributed towards disease pathogenesis. In view
      of the recent advances in utilizing cytokine profiles for the development of
      biological macromolecules, beneficial in the management of certain intractable
      immune-mediated disorders, these recently characterized cytokines (IL-35 and IL
      37) offer potential as reasonable targets for the discovery of novel immune
      modulating anti-inflammatory therapies. A detailed comprehension of their
      sophisticated regulatory mechanisms and patterns of expression may provide unique
      opportunities for clinical application as highly selective and target specific
      therapeutic agents. This review seeks to summarize the recent advancements in
      discerning the dynamics, mechanisms, immunoregulatory and anti-inflammatory
      actions of IL-35 and IL-37 as they relate to disease pathogenesis.

PMID- 29641435
TI  - NIR-Emitting Alloyed CdTeSe QDs and Organic Dye Assemblies: A Nontoxic, Stable,
      and Efficient FRET System.
AB  - In the present work, we synthesize Near Infrared (NIR)-emitting alloyed
      mercaptopropionic acid (MPA)-capped CdTeSe quantum dots (QDs) in a single-step
      one-hour process, without the use of an inert atmosphere or any pyrophoric
      ligands. The quantum dots are water soluble, non-toxic, and highly photostable
      and have high quantum yields (QYs) up to 84%. The alloyed MPA-capped CdTeSe QDs
      exhibit a red-shifted emission, whose color can be tuned between visible and NIR
      regions (608-750 nm) by controlling the Te:Se molar ratio in the precursor
      mixtures and/or changing the time reaction. The MPA-capped QDs were characterized
      by UV-visible absorption spectroscopy, fluorescence spectroscopy, transmission
      electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDS), and zeta
      potential measurements. Photostability studies were performed by irradiating the
      QDs with a high-power xenon lamp. The ternary MPA-CdTeSe QDs showed greater
      photostability than the corresponding binary MPA-CdTe QDs. We report the Forster
      resonance energy transfer (FRET) from the MPA-capped CdTeSe QDs as energy donors
      and Cyanine5 NHS-ester (Cy5) dye as an energy acceptor with efficiency (E) up to
      95%. The distance between the QDs and dye (r), the Forster distance (R0), and the
      binding constant (K) are reported. Additionally, cytocompatibility and cell
      internalization experiments conducted on human cancer cells (HeLa) cells revealed
      that alloyed MPA-capped CdTeSe QDs are more cytocompatible than MPA-capped CdTe
      QDs and are capable of ordering homogeneously all over the cytoplasm, which
      allows their use as potential safe, green donors for biological FRET
      applications.

PMID- 29641436
TI  - Social Interventions to Prevent Heat-Related Mortality in the Older Adult in
      Rome, Italy: A Quasi-Experimental Study.
AB  - This study focuses on the impact of a program aimed at reducing heat-related
      mortality among older adults residing in central Rome by counteracting social
      isolation. The mortality of citizens over the age of 75 living in three Urban
      Areas (UAs) located in central Rome is compared with that of the residents of
      four adjacent UAs during the summer of 2015. The data, broken down by UA, were
      provided by the Statistical Office of the Municipality of Rome, which gathers
      them on a routine basis. During the summer of 2015, 167 deaths were recorded in
      those UAs in which the Long Live the Elderly (LLE) program was active and 169 in
      those in which it was not, implying cumulative mortality rates of 250/00 (SD +/-
      1.4; Cl 95%: 23-29) and 290/00 (SD +/- 6.7; Cl 95%: 17-43), respectively.
      Relative to the summer of 2014, the increase of deaths during the summer of 2015
      was greater in UAs in which the LLE program had not been implemented (+97.3% vs.
      +48.8%). In conclusion, the paper shows the impact of a community-based active
      monitoring program, focused on strengthening individual relationship networks and
      the social capital of the community, on mortality in those over 75 during heat
      waves.

PMID- 29641437
TI  - Dietary Behaviors and Caregiver Perceptions of Overweight and Obesity among
      Chinese Preschool Children.
AB  - Introduction: Early childhood obesity in China has become a pressing public
      health concern. A substantial barrier to healthy weight management is poor
      parental recognition of child overweight. This study examined the relationship
      between caregiver perceptions of child weight and dietary practices. Methods: A
      total of 364 children between 2 and 6 years old from six urban preschools in
      Changsha (China) were included in a cross-sectional study. Information on
      household demographics, health behaviors, and caregiver attitudes was collected
      through a self-administered caregiver questionnaire. Chi-squared tests, t-tests,
      and multivariable logistic regression analysis were used to determine the
      relationship between caregiver perceptions, dietary behaviors, and child weight
      status. Results: Over 60% of caregivers with overweight/obese children
      underestimated their children's weight status. These caregivers were less likely
      to worry about weight and restrict their children's dietary intakes. Children of
      caregivers who incorrectly classified their weights were also more likely to have
      a poor appetite. Caregivers of male children and those from families with incomes
      between 7000 and 11,000 Ren Min Bi (RMB) were more likely to underestimate weight
      compared to caregivers with daughters and those from higher income households.
      Conclusions: Although accurate weight perception may be important for motivating
      healthy behavioral changes, it may also lead to greater restriction of children's
      diets, which has been linked to long-term weight gain. Interventions to improve
      awareness of child overweight should be coupled with efforts that teach
      caregivers about healthy weight management strategies.

PMID- 29641438
TI  - Localization Microscopy of Actin Cytoskeleton in Human Platelets.
AB  - Here, we measure the actin cytoskeleton arrangement of different morphological
      states of human platelets using a new protocol for photo-switching of rhodamine
      class fluorophores. A new medium composition was established for imaging the
      cytoskeleton using Alexa Fluor 488 conjugated to phalloidin. Morphological states
      of platelets bound to a glass substrate are visualized and quantified by two
      dimensional localization microscopy at nanoscopic resolution. Marker-less drift
      correction yields localization of individual Alexa 488 conjugated to phalloidin
      with a positional accuracy of 12 nm.

PMID- 29641439
TI  - Exploring Behavioral Correlates of Afferent Inhibition.
AB  - (1) Background: Afferent inhibition is the attenuation of the muscle response
      evoked from transcranial magnetic stimulation (TMS) by a prior conditioning
      electrical stimulus to a peripheral nerve. It is unclear whether the magnitude of
      afferent inhibition relates to sensation and movement; (2) Methods: 24 healthy,
      young adults were tested. Short-latency afferent inhibition (SAI) and long
      latency afferent inhibition (LAI) were obtained following median and digital
      nerve stimulation. Temporal tactile acuity was assessed with a temporal order
      judgement (TOJ) task, spatial tactile acuity was assessed using a grating
      orientation task (GOT), and fine manual dexterity was assessed with the Pegboard
      task; (3) Results: Correlation analyses revealed no association between the
      magnitude of SAI or LAI with performance on the TOJ, GOT, or Pegboard tasks; (4)
      Conclusion: The magnitude of SAI and LAI does not relate to performance on the
      sensory and motor tasks tested. Future studies are needed to better understand
      whether the afferent inhibition phenomenon relates to human behavior.

PMID- 29641440
TI  - Almonds and Cardiovascular Health: A Review.
AB  - Several preventive strategies to reduce dyslipidemia have been suggested, of
      which dietary modification features as an important one. Dyslipidemia is a major
      risk factor for coronary heart disease and strategies to manage dyslipidemia have
      been shown to reduce the incidence of cardiovascular disease (CVD). Although
      there are proven pharmacological therapies to help manage this condition,
      nutritional interventions are a safer option to help prevent and manage
      dyslipidemia. Addition of almonds in the daily diet has been proposed to
      beneficially impact the lipid profile. This review critically examines the
      available evidence assessing the effect of almonds on dyslipidemia in the South
      Asian (particularly Indian) context. An extensive review comprised of
      epidemiological studies, clinical trials, meta-analyses, and systematic reviews
      was conducted from published literature from across the world. Studies examining
      the effect of almonds on different aspects of dyslipidemia viz. high low-density
      lipoprotein-cholesterol (LDL-C), low high-density lipoprotein-cholesterol (HDL
      C), triglyceridaemia, and high total cholesterol levels have been included. In
      several studies, almonds have been shown to reduce LDL-C-which is a known risk
      factor for CHD-and the effect of almonds has been well documented in systematic
      reviews and meta-analysis of clinical trials. Addition of almonds in the diet has
      been shown to not only to reduce LDL-C levels, but also to maintain HDL-C levels.
      This review provides information about the use of this simple nutritional
      strategy which may help manage known major risk factors for heart disease, such
      as high LDL-C and low HDL-C levels especially in the context of South Asians.

PMID- 29641441
TI  - Cancer Services and Their Initiatives to Improve the Care of Indigenous
      Australians.
AB  - Indigenous Australians continue to experience significantly poorer outcomes from
      cancer than non-Indigenous Australians. Despite the importance of culturally
      appropriate cancer services in improving outcomes, there is a lack of awareness
      of current programs and initiatives that are aimed at meeting the needs of
      Indigenous patients. Telephone interviews were used to identify and describe the
      Indigenous-specific programs and initiatives that are implemented in a subset of
      the services that participated in a larger national online survey of cancer
      treatment services. Fourteen services located across Australia participated in
      the interviews. Participants identified a number of factors that were seen as
      critical to delivering culturally appropriate treatment and support, including
      having a trained workforce with effective cross-cultural communication skills,
      providing best practice care, and improving the knowledge, attitudes, and
      understanding of cancer by Indigenous people. However, over a third of
      participants were not sure how their service compared with others, indicating
      that they were not aware of how other services are doing in this field. There are
      currently many Indigenous-specific programs and initiatives that are aimed at
      providing culturally appropriate treatment and supporting Indigenous people
      affected by cancer across Australia. However, details of these initiatives are
      not widely known and barriers to information sharing exist. Further research in
      this area is needed to evaluate programs and initiatives and showcase the
      effective approaches to Indigenous cancer care.

PMID- 29641442
TI  - Bovine Peripheral Blood Mononuclear Cells Are More Sensitive to Deoxynivalenol
      Than Those Derived from Poultry and Swine.
AB  - Deoxynivalenol (DON) is one of the most prevalent mycotoxins, contaminating
      cereals and cereal-derived products. Its derivative deepoxy-deoxynivalenol (DOM
      1) is produced by certain bacteria, which either occur naturally or are
      supplemented in feed additive. DON-induced impairments in protein synthesis are
      particularly problematic for highly proliferating immune cells. This study
      provides the first comparison of the effects of DON and DOM-1 on the concanavalin
      A-induced proliferation of porcine, chicken, and bovine peripheral blood
      mononuclear cells (PBMCs). Therefore, isolated PBMCs were treated with DON (0.01
      3.37 uM) and DOM-1 (1.39-357 uM) separately, and proliferation was measured using
      a bromodeoxyuridine (BrdU) assay. Although pigs are considered highly sensitive
      to DON, the present study revealed a substantially higher sensitivity of bovine
      (IC50 = 0.314 uM) PBMCs compared to chicken (IC50 = 0.691 uM) and porcine (IC50 =
      0.693 uM) PBMCs. Analyses on the proliferation of bovine T-cell subsets showed
      that all major subsets, namely, CD4+, CD8beta+, and gammadelta T cells, were
      affected to a similar extent. In contrast, DOM-1 did not affect bovine PBMCs, but
      reduced the proliferation of chicken and porcine PBMCs at the highest tested
      concentration (357 uM). Results confirm the necessity of feed additives
      containing DON-to-DOM-1-transforming bacteria and highlights species-specific
      differences in the DON sensitivity of immune cells.

PMID- 29641443
TI  - Effects of Calcination Holding Time on Properties of Wide Band Gap Willemite
      Semiconductor Nanoparticles by the Polymer Thermal Treatment Method.
AB  - Willemite is a wide band gap semiconductor used in modern day technology for
      optoelectronics application. In this study, a new simple technique with less
      energy consumption is proposed. Willemite nanoparticles (NPs) were produced via a
      water-based solution consisting of a metallic precursor, polyvinylpyrrolidone
      (PVP), and underwent a calcination process at 900  degrees C for several holding
      times between 1-4 h. The FT-IR and Raman spectra indicated the presence of metal
      oxide bands as well as the effective removal of PVP. The degree of the
      crystallization and formation of the NPs were determined by XRD. The mean
      crystallite size of the NPs was between 18.23-27.40 nm. The morphology, particle
      shape and size distribution were viewed with HR-TEM and FESEM analysis. The
      willemite NPs aggregate from the smaller to larger particles with an increase in
      calcination holding time from 1-4 h with the sizes ranging between 19.74-29.71
      nm. The energy values obtained from the experimental band gap decreased with
      increasing the holding time over the range of 5.39 eV at 1 h to at 5.27 at 4 h.
      These values match well with band gap obtained from the Mott and Davis model for
      direct transition. The findings in this study are very promising and can justify
      the use of these novel materials as a potential candidate for green luminescent
      optoelectronic applications.

PMID- 29641444
TI  - Fucoxanthin and Polyunsaturated Fatty Acids Co-Extraction by a Green Process.
AB  - By their autotrophic nature and their molecular richness, microalgae are serious
      assets in the context of current environmental and societal challenges. Some
      species produce both omega-3 long chain polyunsaturated fatty acids (PUFAs) and
      xanthophylls, two molecular families widely studied for their bioactivities in
      the fields of nutrition and cosmetics. Whereas most studies separately deal with
      the two families, synergies could be exploited with extracts containing both
      PUFAs and xanthophylls. The purpose of our work was to determine cost effective
      and eco-friendly parameters for their co-extraction. The effect of several
      parameters (solvent, solvent/biomass ratio, temperature, duration) were studied,
      using two microalgal species, the non-calcifying Haptophyta Tisochrysis lutea,
      and the diatom Phaeodactylum tricornutum, that presents a silicified frustule.
      Analyses of PUFAs and fucoxanthin (Fx), the main xanthophyll, allowed to compare
      kinetics and extraction yields between experimental protocols. Co-extraction
      yields achieved using 96% ethanol as solvent were 100% for Fx and docosahexaenoic
      acid (DHA) in one hour from T. lutea biomass, and respectively 95% and 89% for Fx
      and eicosapentaenoic acid (EPA) in eight hours from P. tricornutum. These
      conditions are compatible with industrial applications.

PMID- 29641445
TI  - DK1 Induces Apoptosis via Mitochondria-Dependent Signaling Pathway in Human Colon
      Carcinoma Cell Lines In Vitro.
AB  - Extensive research has been done in the search for innovative treatments against
      colon adenocarcinomas; however, the incidence rate of patients remains a major
      cause of cancer-related deaths in Malaysia. Natural bioactive compounds such as
      curcumin have been substantially studied as an alternative to anticancer drug
      therapies and have been surmised as a potent agent but, nevertheless, remain
      deficient due to its poor cellular uptake. Therefore, efforts now have shifted
      toward mimicking curcumin to synthesize novel compounds sharing similar effects.
      A synthetic analog, (Z)-3-hydroxy-1-(2-hydroxyphenyl)-3-phenylprop-2-ene-1-one
      (DK1), was recently synthesized and reported to confer improved bioavailability
      and selectivity toward human breast cancer cells. This study, therefore, aims to
      assess the anticancer mechanism of DK1 in relation to the induction of in vitro
      cell death in selected human colon cancer cell lines. Using the3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay, the
      cytotoxicity of DK1 towards HT29 and SW620 cell lines were investigated. Acridine
      orange/propidium iodide (AO/PI) dual-staining assay and flow cytometry analyses
      (cell cycle analysis, Annexin/V-FITC and JC-1 assays) were incorporated to
      determine the mode of cell death. To further determine the mechanism of cell
      death, quantitative real-time polymerase chain reaction (qRT-PCR) and proteome
      profiling were conducted. Results from this study suggest that DK1 induced
      changes in cell morphology, leading to a decrease in cell viability and
      subsequent induction of apoptosis. DK1 treatment inhibited cell viability and
      proliferation 48 h post treatment with IC50 values of 7.5 +/- 1.6 uM for HT29
      cells and 14.5 +/- 4.3 uM for SW620 cells, causing cell cycle arrest with
      increased accumulation of cell populations at the sub-G0/G1phaseof 74% and 23%,
      respectively. Flow cytometry analyses showed that DK1 treatment in cancer cells
      induced apoptosis, as indicated by DNA fragmentation and depolarization of the
      mitochondrial membrane. qRT-PCR results show significant upregulation in the
      expression of caspase-9 in both HT29 and SW620 cell lines, further supporting
      that cell death induction by DK1 is via an intrinsic pathway. These outcomes,
      therefore, demonstrate DK1 as a potential anticancer agent for colon
      adenocarcinoma due to its anti-apoptotic attributes.

PMID- 29641446
TI  - The JAK2 GGCC (46/1) Haplotype in Myeloproliferative Neoplasms: Causal or Random?
AB  - The germline JAK2 haplotype known as "GGCC or 46/1 haplotype"
      (haplotypeGGCC_46/1) consists of a combination of single nucleotide polymorphisms
      (SNPs) mapping in a region of about 250 kb, extending from the JAK2 intron 10 to
      the Insulin-like 4 (INLS4) gene. Four main SNPs (rs3780367, rs10974944,
      rs12343867, and rs1159782) generating a "GGCC" combination are more frequently
      indicated to represent the JAK2 haplotype. These SNPs are inherited together and
      are frequently associated with the onset of myeloproliferative neoplasms (MPN)
      positive for both JAK2 V617 and exon 12 mutations. The association between the
      JAK2 haplotypeGGCC_46/1 and mutations in other genes, such as thrombopoietin
      receptor (MPL) and calreticulin (CALR), or the association with triple negative
      MPN, is still controversial. This review provides an overview of the frequency
      and the role of the JAK2 haplotypeGGCC_46/1 in the pathogenesis of different
      myeloid neoplasms and describes the hypothetical mechanisms at the basis of the
      association with JAK2 gene mutations. Moreover, possible clinical implications
      are discussed, as different papers reported contrasting data about the
      correlation between the JAK2 haplotypeGGCC_46/1 and blood cell count, survival,
      or disease progression.

PMID- 29641447
TI  - Glucose-Dependent Insulinotropic Polypeptide Mitigates 6-OHDA-Induced Behavioral
      Impairments in Parkinsonian Rats.
AB  - In the present study, the effectiveness of glucose-dependent insulinotropic
      polypeptide (GIP) was evaluated by behavioral tests in 6-hydroxydopamine (6-OHDA)
      hemi-parkinsonian (PD) rats. Pharmacokinetic measurements of GIP were carried out
      at the same dose studied behaviorally, as well as at a lower dose used
      previously. GIP was delivered by subcutaneous administration (s.c.) using
      implanted ALZET micro-osmotic pumps. After two days of pre-treatment, male
      Sprague Dawley rats received a single unilateral injection of 6-OHDA into the
      medial forebrain bundle (MFB). The neuroprotective effects of GIP were evaluated
      by apomorphine-induced contralateral rotations, as well as by locomotor and
      anxiety-like behaviors in open-field tests. Concentrations of human active and
      total GIP were measured in plasma during a five-day treatment period by ELISA and
      were found to be within a clinically translatable range. GIP pretreatment reduced
      behavioral abnormalities induced by the unilateral nigrostriatal dopamine (DA)
      lesion produced by 6-OHDA, and thus may be a novel target for PD therapeutic
      development.

PMID- 29641450
TI  - Age-Dependent Developmental Response to Temperature: An Examination of the Rarely
      Tested Phenomenon in Two Species (Gypsy Moth (Lymantria dispar) and Winter Moth
      (Operophtera brumata)).
AB  - The pervading paradigm in insect phenology models is that the response to a given
      temperature does not vary within a life stage. The developmental rate functions
      that have been developed for general use, or for specific insects, have for the
      most part been temperature-dependent but not age-dependent, except where age is
      an ordinal variable designating the larval instar. Age dependence, where age is a
      continuous variable, is not often reported (or investigated), and is rarely
      included in phenology models. I provide a short review of the seldom-investigated
      phenomenon of age dependence in developmental response to temperature, and
      compare the derivation of the winter moth egg phenology model by Salis et al. to
      the derivation of another egg phenology model with age-dependent responses to
      temperature I discuss some probable reasons for the discrepancies (acknowledged
      by Salis et al. between modelled and observed developmental rates of the winter
      moth, and discuss the contribution that geographically robust phenology models
      can make to estimates of species distributions.

PMID- 29641448
TI  - Identification and Evolution of TGF-beta Signaling Pathway Members in Twenty-Four
      Animal Species and Expression in Tilapia.
AB  - Transforming growth factor beta (TGF-beta) signaling controls diverse cellular
      processes during embryogenesis as well as in mature tissues of multicellular
      animals. Here we carried out a comprehensive analysis of TGF-beta pathway members
      in 24 representative animal species. The appearance of the TGF-beta pathway was
      intrinsically linked to the emergence of metazoan. The total number of TGF-beta
      ligands, receptors, and smads changed slightly in all invertebrates and jawless
      vertebrates analyzed. In contrast, expansion of the pathway members, especially
      ligands, was observed in jawed vertebrates most likely due to the second round of
      whole genome duplication (2R) and additional rounds in teleosts. Duplications of
      TGFB2, TGFBR2, ACVR1, SMAD4 and SMAD6, which were resulted from 2R, were first
      isolated. Type II receptors may be originated from the ACVR2-like ancestor.
      Interestingly, AMHR2 was not identified in Chimaeriformes and Cypriniformes even
      though they had the ligand AMH. Based on transcriptome data, TGF-beta ligands
      exhibited a tissue-specific expression especially in the heart and gonads.
      However, most receptors and smads were expressed in multiple tissues indicating
      they were shared by different ligands. Spatial and temporal expression profiles
      of 8 genes in gonads of different developmental stages provided a fundamental
      clue for understanding their important roles in sex determination and
      reproduction. Taken together, our findings provided a global insight into the
      phylogeny and expression patterns of the TGF-beta pathway genes, and hence
      contribute to the greater understanding of their biological roles in the organism
      especially in teleosts.

PMID- 29641449
TI  - Delivery of Proapoptotic Agents in Glioma Cell Lines by TSPO Ligand-Dextran
      Nanogels.
AB  - Translocator protein 18-kDa (TSPO) is a versatile mitochondrial target for
      molecular imaging and therapy. Moreover, selective TSPO ligands have been widely
      investigated for diagnostic purposes and explored to target drug delivery systems
      directed to cancer cells overexpressing TSPO. Indeed, poly(d,l-lactic-co-glycolic
      acid (PLGA) polymers and nanocarriers decorated with TSPO ligands are capable of
      transporting TSPO ligands inside cancer cells, inducing survival inhibition in
      cancer cells and producing mitochondrial morphology modification. The aim of this
      work was to prepare nanogels (NGs) made with TSPO ligand dextran conjugates (TSPO
      Dex) that are useful as potential delivery systems of two TSPO ligands as
      apoptotic agents. Synthesis and complete characterization of TSPO-dextran
      conjugates, an average molecular weights analysis, TSPO ligand release profiles,
      thermal behaviour and swelling studies were achieved. NG preparation,
      characterization and in vitro biological studies were also performed. The release
      of TSPO ligands released from dextran conjugates at 37  degrees C occurred in
      human serum at a faster rate than that detected in phosphate buffer. Cytotoxicity
      studies demonstrated that NGs produced from TSPO ligand-dextran conjugates induce
      survival inhibition in rat C6 glioma cell lines. Cellular uptake was also proven
      by fluorescence microscopy.

PMID- 29641451
TI  - Near-Infrared Spectroscopic Method for Monitoring Water Content in Epoxy Resins
      and Fiber-Reinforced Composites.
AB  - Monitoring water content and predicting the water-induced drop in strength of
      fiber-reinforced composites are of great importance for the oil and gas and
      marine industries. Fourier transform infrared (FTIR) spectroscopic methods are
      broadly available and often used for process and quality control in industrial
      applications. A benefit of using such spectroscopic methods over the conventional
      gravimetric analysis is the possibility to deduce the mass of an absolutely dry
      material and subsequently the true water content, which is an important indicator
      of water content-dependent properties. The objective of this study is to develop
      an efficient and detailed method for estimating the water content in epoxy resins
      and fiber-reinforced composites. In this study, Fourier transform near-infrared
      (FT-NIR) spectroscopy was applied to measure the water content of amine-epoxy
      neat resin. The method was developed and successfully extended to glass fiber
      reinforced composite materials. Based on extensive measurements of neat resin and
      composite samples of varying water content and thickness, regression was
      performed, and the quantitative absorbance dependence on water content in the
      material was established. The mass of an absolutely dry resin was identified, and
      the true water content was obtained. The method was related to the Beer-Lambert
      law and explained in such terms. A detailed spectroscopic method for measuring
      water content in resins and fiber-reinforced composites was developed and
      described.

PMID- 29641452
TI  - A Novel "Off-On" Fluorescent Probe Based on Carbon Nitride Nanoribbons for the
      Detection of Citrate Anion and Live Cell Imaging.
AB  - A novel fluorescent "off-on" probe based on carbon nitride (C3N4) nanoribbons was
      developed for citrate anion (C6H5O73-) detection. The fluorescence of C3N4
      nanoribbons can be quenched by Cu2+ and then recovered by the addition of C6H5O73
      , because the chelation between C6H5O73- and Cu2+ blocks the electron transfer
      between Cu2+ and C3N4 nanoribbons. The turn-on fluorescent sensor using this
      fluorescent "off-on" probe can detect C6H5O73- rapidly and selectively, showing a
      wide detection linear range (1~400 MUM) and a low detection limit (0.78 MUM) in
      aqueous solutions. Importantly, this C3N4 nanoribbon-based "off-on" probe
      exhibits good biocompatibility and can be used as fluorescent visualizer for
      exogenous C6H5O73- in HeLa cells.

PMID- 29641453
TI  - Edge-Aware Unidirectional Total Variation Model for Stripe Non-Uniformity
      Correction.
AB  - The problem of stripe non-uniformity in array-based infrared imaging systems has
      been the focus of many research studies. Among the proposed correction
      techniques, total variation models have been proven to significantly reduce the
      effect of this type of noise on the captured image. However, they also cause the
      loss of some image details and textures due to over-smoothing effect. In this
      paper, a correction scheme is proposed based on unidirectional variation model to
      exploit the direction characteristic of the stripe noise, in which an edge-aware
      weighting is incorporated to convey image structure retaining ability to the
      overall algorithm. Moreover, a statistical-based regularization is also
      introduced to further enhance correction performance around strong edges. The
      proposed approach is thoroughly scrutinized and compared to the state-of-the-art
      de-striping techniques using real stripe non-uniform images. Results demonstrate
      a significant improvement in edge preservation with better correction
      performance.

PMID- 29641454
TI  - The Potential Health Benefits of Noni Juice: A Review of Human Intervention
      Studies.
AB  - Noni juice is a globally popular health beverage originating in the tropics.
      Traditional Tahitian healers believe the noni plant to be useful for a wide range
      of maladies, and noni juice consumers throughout the world have similar
      perceptions. Nevertheless, human clinical trials are necessary for a precise
      understanding of what the health benefits of noni juice are. A review of
      published human intervention studies suggests that noni juice may provide
      protection against tobacco smoke-induced DNA damage, blood lipid and homocysteine
      elevation as well as systemic inflammation. Human intervention studies also
      indicate that noni juice may improve joint health, increase physical endurance,
      increase immune activity, inhibit glycation of proteins, aid weight management,
      help maintain bone health in women, help maintain normal blood pressure, and
      improve gum health. Further, these studies point to notable antioxidant activity
      in noni juice, more so than other fruit juices which served as trial placebos. It
      is this antioxidant effect and its interaction with the immune system and
      inflammation pathways that may account for many of the observed health benefits
      of noni juice. However, the existing evidence does have some limitations as far
      as its general application to noni juice products; all the peer-reviewed human
      interventions studies to date have involved only one source of French Polynesian
      noni juice. Geographical factors and variations in processing methods are known
      to produce commercial noni juice products with divergent phytochemical and
      nutrient compositions. Therefore, other sources of noni products may have
      different toxicological and pharmacological profiles.

PMID- 29641455
TI  - A Flexible Sensing Unit Manufacturing Method of Electrochemical Seismic Sensor.
AB  - This paper presents an electrochemical seismic sensor in which paraylene was used
      as a substrate and insulating layer of micro-fabricated electrodes, enabling the
      detection of seismic signals with enhanced sensitivities in comparison to silicon
      based counterparts. Based on microfabrication, paralene-based electrochemical
      seismic sensors were fabricated in which the thickness of the insulating spacer
      was 6.7 MUm. Compared to silicon-based counterparts with ~100 MUm insulating
      layers, the parylene-based devices produced higher sensitivities of 490.3 +/- 6.1
      V/(m/s) vs. 192.2 +/- 1.9 V/(m/s) at 0.1 Hz, 4764.4 +/- 18 V/(m/s) vs. 318.9 +/-
      6.5 V/(m/s) at 1 Hz, and 4128.1 +/- 38.3 V/(m/s) vs. 254.5 +/- 4.2 V/(m/s) at 10
      Hz. In addition, the outputs of the parylene vs. silicon devices in response to
      two transit inputs were compared, producing peak responses of 2.97 V vs. 0.22 V
      and 2.41 V vs. 0.19 V, respectively. Furthermore, the self-noises of parylene vs.
      silicon-based devices were compared as follows: -82.3 +/- 3.9 dB vs. -90.4 +/-
      9.4 dB at 0.1 Hz, -75.7 +/- 7.3 dB vs. -98.2 +/- 9.9 dB at 1 Hz, and -62.4 +/-
      7.7 dB vs. -91.1 +/- 8.1 dB at 10 Hz. The developed parylene-based
      electrochemical seismic sensors may function as an enabling technique for further
      detection of seismic motions in various applications.

PMID- 29641456
TI  - Preparation of Hybrid Nanoparticle Nucleating Agents and Their Effects on the
      Crystallization Behavior of Poly(ethylene terephthalate).
AB  - In this research contribution, the primary objective was to enhance the
      crystallization behavior of poly(ethylene terephthalate) (PET). To accomplish
      this tack, three kinds of new nucleating agents SiO2-diethylene glycol-LMPET (PET
      3), SiO2-triethylene glycol-LMPET(PET-4) and SiO2-tetraethylene glycol-LMPET (PET
      5) nucleating agents were prepared via grafting different oligomers (diethylene
      glycol; triethylene glycol and tetraethylene glycol) to the surface of nano-SiO2
      and then linking to the low molecular weight poly(ethylene terephthalate)
      (LMPET). These nano-particle nucleating agents facilitated the crystallization of
      PET. Differential scanning calorimetry (DSC) studies of the composites that pure
      PET blended with PET-3, PET-4 and PET-5 indicated that the longer ethoxy segment
      in the nucleating agents exhibited (i) higher degrees of crystallinity; (ii)
      faster rates of crystallization; and (iii) higher crystallization temperatures.
      The Jeziorny method was employed to analyze the non-isothermal crystallization
      kinetics of the composites. These works demonstrated that the PET-3, PET-4 and
      PET-5 were attractive nucleating agents for poly(ethylene terephthalate), and the
      longer the chain length of the ethoxy segment in the nucleating agents, the more
      efficient the nucleation effect.

PMID- 29641457
TI  - Facile Syntheses and Molecular-Docking of Novel Substituted 3,4-Dimethyl-1H
      pyrrole-2-carboxamide/carbohydrazide Analogues with Antimicrobial and Antifungal
      Properties.
AB  - The article describes the use of facile one-pot, high-yielding reactions to
      synthesize substituted 3,4-dimethyl-1H-pyrrole-2-carboxamides 3a-m and
      carbohydrazide analogues 5a-l as potential antifungal and antimicrobial agents.
      The structural identity and purity of the synthesized compounds were assigned
      based on appropriate spectroscopic techniques. Synthesized compounds were
      assessed in vitro for antifungal and antibacterial activity. The compounds 5h, 5i
      and 5j were found to be the most potent against Aspergillusfumigatus, with MIC
      values of 0.039 mg/mL. The compound 5f bearing a 2, 6-dichloro group on the
      phenyl ring was found to be the most active broad spectrum antibacterial agent
      with a MIC value of 0.039 mg/mL. The mode of action of the most promising
      antifungal compounds (one representative from each series; 3j and 5h) was
      established by their molecular docking with the active site of sterol 14alpha
      demethylase. Molecular docking studies revealed a highly spontaneous binding
      ability of the tested compounds in the access channel away from catalytic heme
      iron of the enzyme, which suggested that the tested compounds inhibit this enzyme
      and would avoid heme iron-related deleterious side effects observed with many
      existing antifungal compounds.

PMID- 29641458
TI  - Epigallocatechin Gallate-Modified Gelatin Sponges Treated by Vacuum Heating as a
      Novel Scaffold for Bone Tissue Engineering.
AB  - Chemical modification of gelatin using epigallocatechin gallate (EGCG) promotes
      bone formation in vivo. However, further improvements are required to increase
      the mechanical strength and bone-forming ability of fabricated EGCG-modified
      gelatin sponges (EGCG-GS) for practical applications in regenerative therapy. In
      the present study, we investigated whether vacuum heating-induced dehydrothermal
      cross-linking of EGCG-GS enhances bone formation in critical-sized rat calvarial
      defects. The bone-forming ability of vacuum-heated EGCG-GS (vhEGCG-GS) and other
      sponges was evaluated by micro-computed tomography and histological staining. The
      degradation of sponges was assessed using protein assays, and cell morphology and
      proliferation were verified by scanning electron microscopy and immunostaining
      using osteoblastic UMR106 cells in vitro. Four weeks after the implantation of
      sponges, greater bone formation was detected for vhEGCG-GS than for EGCG-GS or
      vacuum-heated gelatin sponges (dehydrothermal cross-linked sponges without EGCG).
      In vitro experiments revealed that the relatively low degradability of vhEGCG-GS
      supports cell attachment, proliferation, and cell-cell communication on the
      matrix. These findings suggest that vacuum heating enhanced the bone forming
      ability of EGCG-GS, possibly via the dehydrothermal cross-linking of EGCG-GS,
      which provides a scaffold for cells, and by maintaining the pharmacological
      effect of EGCG.

PMID- 29641461
TI  - Identification of an ACE-Inhibitory Peptide from Walnut Protein and Its
      Evaluation of the Inhibitory Mechanism.
AB  - In the present study, a novel angiotensin I-converting enzyme inhibitory (ACE
      inhibitory) peptide, EPNGLLLPQY, derived from walnut seed storage protein,
      fragment residues 80-89, was identified by ultra-high performance liquid
      chromatography electrospray ionization quadrupole time of flight mass
      spectrometry (UPLC-ESI-Q-TOF-MS/MS) from walnut protein hydrolysate. The IC50
      value of the peptide was 233.178 MUM, which was determined by the high
      performance liquid chromatography method by measuring the amount of hippuric acid
      (HA) generated from the ACE decomposition substrate (hippuryl-l-histidyl-l
      leucine (HHL) to assess the ACE activity. Enzyme inhibitory kinetics of the
      peptide against ACE were also conducted, by which the inhibitory mechanism of ACE
      inhibitory peptide was confirmed. Moreover, molecular docking was simulated by
      Discovery Studio 2017 R2 software to provide the potential mechanisms underlying
      the ACE-inhibitory activity of EPNGLLLPQY.

PMID- 29641460
TI  - Characteristics of Milk Fermented by Streptococcus thermophilus MGA45-4 and the
      Profiles of Associated Volatile Compounds during Fermentation and Storage.
AB  - The lactic acid bacterium Streptococcus thermophilus is a major starter culture
      for the production of dairy products. In this study, the physiochemical
      characteristics of milk fermented by the MGA45-4 isolate of S. thermophilus were
      analyzed. Our data indicate that milk fermented using S. thermophilus MGA45-4
      maintained a high viable cell count (8.86 log10 colony-forming units/mL), and a
      relatively high pH (4.4), viscosity (834.33 mPa.s), and water holding capacity
      (40.85%) during 14 days of storage. By analyzing the volatile compound profile
      using solid-phase microextraction and gas chromatography/mass spectrometry, we
      identified 73 volatile compounds in the fermented milk product, including five
      carboxylic acids, 21 aldehydes, 13 ketones, 16 alcohols, five esters, and 13
      aromatic carbohydrates. According to the odor activity values, 11 of these
      volatile compounds were found to play a key role in producing the characteristic
      flavor of fermented milk, particularly octanal, nonanal, hexanal, 2,3
      butanedione, and 1-octen-3-ol, which had the highest odor activity values among
      all compounds analyzed. These findings thus provide more insights in the
      chemical/molecular characteristics of milk fermented using S. thermophilus, which
      may provide a basis for improving dairy product flavor/odor during the process of
      fermentation and storage.

PMID- 29641462
TI  - Multisensory Integration Strategy for Modality-Specific Loss of Inhibition
      Control in Older Adults.
AB  - Older adults are known to have lesser cognitive control capability and greater
      susceptibility to distraction than young adults. Previous studies have reported
      age-related problems in selective attention and inhibitory control, yielding
      mixed results depending on modality and context in which stimuli and tasks were
      presented. The purpose of the study was to empirically demonstrate a modality
      specific loss of inhibitory control in processing audio-visual information with
      ageing. A group of 30 young adults (mean age = 25.23, Standar Desviation (SD) =
      1.86) and 22 older adults (mean age = 55.91, SD = 4.92) performed the audio
      visual contour identification task (AV-CIT). We compared performance of
      visual/auditory identification (Uni-V, Uni-A) with that of visual/auditory
      identification in the presence of distraction in counterpart modality (Multi-V,
      Multi-A). The findings showed a modality-specific effect on inhibitory control.
      Uni-V performance was significantly better than Multi-V, indicating that auditory
      distraction significantly hampered visual target identification. However, Multi-A
      performance was significantly enhanced compared to Uni-A, indicating that
      auditory target performance was significantly enhanced by visual distraction.
      Additional analysis showed an age-specific effect on enhancement between Uni-A
      and Multi-A depending on the level of visual inhibition. Together, our findings
      indicated that the loss of visual inhibitory control was beneficial for the
      auditory target identification presented in a multimodal context in older adults.
      A likely multisensory information processing strategy in the older adults was
      further discussed in relation to aged cognition.

PMID- 29641459
TI  - An Overview of Novel Dietary Supplements and Food Ingredients in Patients with
      Metabolic Syndrome and Non-Alcoholic Fatty Liver Disease.
AB  - Metabolic syndrome (MetS) is characterized by interconnected factors related to
      metabolic disturbances, and is directly related to the occurrence of some
      diseases such as cardiovascular diseases and type 2 diabetes. MetS is described
      as one or both of insulin resistance and visceral adiposity, considered the
      initial causes of abnormalities that include hyperglycemia, elevated blood
      pressure, dyslipidemia, elevated inflammatory markers, and prothrombotic state,
      as well as polycystic ovarian syndrome in women. Other than in MetS, visceral
      adiposity and the pro-inflammatory state are also key in the development of non
      alcoholic fatty liver disease (NAFLD), which is the most prevalent chronic liver
      disease in modern society. Both MetS and NAFLD are related to diet and lifestyle,
      and their treatment may be influenced by dietary pattern changes and the use of
      certain dietary supplements. This study aimed to review the role of food
      ingredients and supplements in the management of MetS and NAFLD specifically in
      human clinical trials. Moreover, bioactive compounds and polyunsaturated fatty
      acids (PUFAs) may be used as strategies for preventing the onset of and treatment
      of metabolic disorders, such as MetS and NAFLD, improving the inflammatory state
      and other comorbidities, such as obesity, dyslipidemias, and cardiovascular
      diseases (CVD).

PMID- 29641464
TI  - Oral Health-Related Quality of Life in Young Adults: A Survey of Russian
      Undergraduate Students.
AB  - BACKGROUND: Oral health (OH) is poor among young adults in Russia, but there is
      little information on OH-related quality of life (OHRQoL) in this population. We
      investigated how socio-demographic factors, self-reported OH characteristics,
      oral health behaviour, and clinically-assessed OH are related to OHRQoL in
      medical and dental students in North-West Russia. METHODS: This cross-sectional
      study included 391 medical and 275 dental Russian undergraduate students aged 18
      25 years. Information on socio-demographic, self-reported OH characteristics, and
      oral health behaviour was obtained from a structured, self-administered
      questionnaire. A clinical examination was performed to assess dental caries
      experience based on the decayed (D) missing (M) filled (F) teeth (T) index;
      Simplified Oral Hygiene Index; and Gingival Index. OHRQoL was measured by the OH
      Impact Profile (OHIP-14). RESULTS: 53.6% of students reported low OHRQoL during
      the last 12 months. Female sex (odds ratio [OR] = 1.48, 95% confidence interval
      [CI]: 1.00-2.19), rural place of childhood residence (OR = 1.56, 95% CI: 1.06
      2.28), poor self-assessed dental aesthetic (OR = 1.75, 95% CI: 1.16-2.64),
      dissatisfaction with mouth and teeth (OR = 2.51, 95% CI: 1.68-3.77), and DMFT
      index (OR = 1.05, 95% CI: 1.01-1.09), were all significantly, independently
      associated with low OHRQoL. CONCLUSION: Socio-demographic factors (rural place of
      childhood residence, female sex), poor self-reported OH characteristics, and high
      DMFT index were associated with low OHRQoL.

PMID- 29641463
TI  - iTRAQ Quantitative Proteomic Analysis of Vitreous from Patients with Retinal
      Detachment.
AB  - Rhegmatogenous retinal detachment (RRD) is a potentially blinding condition
      characterized by a physical separation between neurosensory retina and retinal
      pigment epithelium. Quantitative proteomics can help to understand the changes
      that occur at the cellular level during RRD, providing additional information
      about the molecular mechanisms underlying its pathogenesis. In the present study,
      iTRAQ labeling was combined with two-dimensional LC-ESI-MS/MS to find expression
      changes in the proteome of vitreous from patients with RRD when compared to
      control samples. A total of 150 proteins were found differentially expressed in
      the vitreous of patients with RRD, including 96 overexpressed and 54
      underexpressed. Several overexpressed proteins, several such as glycolytic
      enzymes (fructose-bisphosphate aldolase A, gamma-enolase, and phosphoglycerate
      kinase 1), glucose transporters (GLUT-1), growth factors (metalloproteinase
      inhibitor 1), and serine protease inhibitors (plasminogen activator inhibitor 1)
      are regulated by HIF-1, which suggests that HIF-1 signaling pathway can be
      triggered in response to RRD. Also, the accumulation of photoreceptor proteins,
      including phosducin, rhodopsin, and s-arrestin, and vimentin in vitreous may
      indicate that photoreceptor degeneration occurs in RRD. Also, the accumulation of
      photoreceptor proteins, including phosducin, rhodopsin, and s-arrestin, and
      vimentin in vitreous may indicate that photoreceptor degeneration occurs in RRD.
      Nevertheless, the differentially expressed proteins found in this study suggest
      that different mechanisms are activated after RRD to promote the survival of
      retinal cells through complex cellular responses.

PMID- 29641465
TI  - Antitumor Effect of Calcium-Mediated Destabilization of Epithelial Growth Factor
      Receptor on Non-Small Cell Lung Carcinoma.
AB  - Despite the development of numerous therapeutics targeting the epithelial growth
      factor receptor (EGFR) for non-small cell lung carcinoma (NSCLC), the application
      of these drugs is limited because of drug resistance. Here, we investigated the
      antitumor effect of calcium-mediated degradation of EGFR pathway-associated
      proteins on NSCLC. First, lactate calcium salt (LCS) was utilized for calcium
      supplementation. Src, alpha-tubulin and EGFR levels were measured after LSC
      treatment, and the proteins were visualized by immunocytochemistry. Calpeptin was
      used to confirm the calcium-mediated effect of LCS on NSCLC. Nuclear expression
      of c-Myc and cyclin D1 was determined to understand the underlying mechanism of
      signal inhibition following EGFR and Src destabilization. The colony formation
      assay and a xenograft animal model were used to confirm the in vitro and in vivo
      antitumor effects, respectively. LCS supplementation reduced Src and alpha
      tubulin expression in NSCLC cells. EGFR was destabilized because of proteolysis
      of Src and alpha-tubulin. c-Myc and cyclin D1 expression levels were also reduced
      following the decrease in the transcriptional co-activation of EGFR and Src.
      Clonogenic ability and tumor growth were significantly inhibited by LSC treatment
      induced EGFR destabilization. These results suggest that other than specifically
      targeting EGFR, proteolysis of associated molecules such as Src or alpha-tubulin
      may effectively exert an antitumor effect on NSCLC via EGFR destabilization.
      Therefore, LCS is expected to be a good candidate for developing novel anti-NSCLC
      therapeutics overcoming chemoresistance.

PMID- 29641466
TI  - In Vitro Dermal Safety Assessment of Silver Nanowires after Acute Exposure:
      Tissue vs. Cell Models.
AB  - Silver nanowires (AgNW) are attractive materials that are anticipated to be
      incorporated into numerous consumer products such as textiles, touchscreen
      display, and medical devices that could be in direct contact with skin. There are
      very few studies on the cellular toxicity of AgNW and no studies that have
      specifically evaluated the potential toxicity from dermal exposure. To address
      this question, we investigated the dermal toxicity after acute exposure of
      polymer-coated AgNW with two sizes using two models, human primary keratinocytes
      and human reconstructed epidermis. In keratinocytes, AgNW are rapidly and
      massively internalized inside cells leading to dose-dependent cytotoxicity that
      was not due to Ag+ release. Analysing our data with different dose metrics, we
      propose that the number of NW is the most appropriate dose-metric for studies of
      AgNW toxicity. In reconstructed epidermis, the results of a standard in vitro
      skin irritation assay classified AgNW as non-irritant to skin and we found no
      evidence of penetration into the deeper layer of the epidermis. The findings show
      that healthy and intact epidermis provides an effective barrier for AgNW,
      although the study does not address potential transport through follicles or
      injured skin. The combined cell and tissue model approach used here is likely to
      provide an important methodology for assessing the risks for skin exposure to
      AgNW from consumer products.

PMID- 29641467
TI  - The Association of Dietary Patterns with High-Risk Human Papillomavirus Infection
      and Cervical Cancer: A Cross-Sectional Study in Italy.
AB  - Specific foods and nutrients help prevent the progression of persistent high-risk
      human papillomavirus (hrHPV) infection to cervical cancer (CC). The aim of this
      study was to investigate dietary patterns which may be associated with hrHPV
      status and the risk of high-grade cervical intraepithelial neoplasia (CIN2+).
      Overall, 539 eligible women, including 127 with CIN2+, were enrolled in a cross
      sectional study, and tested for hrHPV infection. Food intake was estimated using
      a food frequency questionnaire. Logistic regression models were applied. Using
      the Mediterranean Diet Score, we demonstrated that, among 252 women with a normal
      cervical epithelium, medium adherence to the Mediterranean diet decreased the
      odds of hrHPV infection when compared to low adherence (adjOR = 0.40, 95%CI =
      0.22-0.73). Using the principal component analysis, we also identified two
      dietary patterns which explained 14.31% of the variance in food groups intake.
      Women in the third and fourth quartiles of the "Western pattern" had higher odds
      of hrHPV infection when compared with first quartile (adjOR = 1.77, 95% CI = 1.04
      3.54 and adjOR = 1.97, 95%CI = 1.14-4.18, respectively). Adjusting for hrHPV
      status and age, women in the third quartile of the "prudent pattern" had lower
      odds of CIN2+ when compared with those in the first quartile (OR = 0.50, 95%CI =
      0.26-0.98). Our study is the first to demonstrate the association of dietary
      patterns with hrHPV infection and CC and discourages unhealthy habits in favour
      of a Mediterranean-like diet.

PMID- 29641468
TI  - Associations of Mediterranean Diet and a Posteriori Derived Dietary Patterns with
      Breast and Lung Cancer Risk: A Case-Control Study.
AB  - Lung cancer in men and breast cancer in women are the most commonly diagnosed
      cancers in Poland and worldwide. Results of studies involving dietary patterns
      (DPs) and breast or lung cancer risk in European countries outside the
      Mediterranean Sea region are limited and inconclusive. This study aimed to
      develop a 'Polish-adapted Mediterranean Diet' ('Polish-aMED') score, and then
      study the associations between the 'Polish-aMED' score and a posteriori-derived
      dietary patterns with breast or lung cancer risk in adult Poles. This pooled
      analysis of two case-control studies involved 560 subjects (280 men, 280 women)
      aged 40-75 years from Northeastern Poland. Diagnoses of breast cancer in 140
      women and lung cancer in 140 men were found. The food frequency consumption of 21
      selected food groups was collected using a 62-item Food Frequency Questionnaire
      (FFQ)-6. The 'Polish-adapted Mediterranean Diet' score which included eight items
      vegetables, fruit, whole grain, fish, legumes, nuts and seeds-as well as the
      ratio of vegetable oils to animal fat and red and processed meat was developed
      (range: 0-8 points). Three DPs were identified in a Principal Component Analysis:
      'Prudent', 'Non-healthy', 'Dressings and sweetened-low-fat dairy'. In a multiple
      logistic regression analysis, two models were created: crude, and adjusted for
      age, sex, type of cancer, Body Mass Index (BMI), socioeconomic status (SES)
      index, overall physical activity, smoking status and alcohol abuse. The risk of
      breast or lung cancer was lower in the average (3-5 points) and high (6-8 points)
      levels of the 'Polish-aMED' score compared to the low (0-2 points) level by 51%
      (odds ratio (OR): 0.49; 95% confidence interval (Cl): 0.30-0.80; p < 0.01;
      adjusted) and 63% (OR: 0.37; 95% Cl: 0.21-0.64; p < 0.001; adjusted),
      respectively. In the middle and upper tertiles compared to the bottom tertile of
      the 'Prudent' DP, the risk of cancer was lower by 38-43% (crude) but was not
      significant after adjustment for confounders. In the upper compared to the bottom
      tertile of the 'Non-healthy' DP, the risk of cancer was higher by 65% (OR: 1.65;
      95% Cl: 1.05-2.59; p < 0.05; adjusted). In conclusion, the Polish adaptation of
      the Mediterranean diet could be considered for adults living in non-Mediterranean
      countries for the prevention of the breast or lung cancers. Future studies should
      explore the role of a traditional Mediterranean diet fitted to local dietary
      patterns of non-Mediterranean Europeans in cancer prevention.

PMID- 29641469
TI  - Free and Bound Phenolic Compound Content and Antioxidant Activity of Different
      Cultivated Blue Highland Barley Varieties from the Qinghai-Tibet Plateau.
AB  - In this study, the polyphenols composition and antioxidant properties of 12 blue
      highland barley varieties planted on the Qinghai-Tibet Plateau area were
      measured. The contents of the free, bound and total phenolic acids varied between
      166.20-237.60, 170.10-240.75 and 336.29-453.94 mg of gallic acid equivalents per
      100 g of dry weight (DW) blue highland barley grains, while the free and bound
      phenolic acids accounted for 50.09% and 49.91% of the total phenolic acids,
      respectively. The contents of the free, bound and total flavones varied among
      20.61-25.59, 14.91-22.38 and 37.91-47.98 mg of catechin equivalents per 100 g of
      dry weight (DW) of blue highland barley grains, while the free and bound flavones
      accounted for 55.90% and 44.10% of the total flavones, respectively. The
      prominent phenolic compounds in the blue hulless barley grains were gallic acid,
      benzoic acid, syringic acid, 4-coumaric acid, naringenin, hesperidin, rutin, (+)
      catechin and quercetin. Among these, protocatechuic acid, chlorogenic acid and
      (+)-catechin were the major phenolic compounds in the free phenolics extract. The
      most abundant bound phenolics were gallic acid, benzoic acid, syringic acid, 4
      coumaric acid, benzoic acid, dimethoxybenzoic acid, naringenin, hesperidin,
      quercetin and rutin. The average contribution of the bound phenolic extract to
      the DPPH* free radical scavenging capacity was higher than 86%, that of free
      phenolic extract to the ABTS*+ free radical scavenging capacity was higher than
      79%, and that of free phenolic (53%) to the FRAP antioxidant activity was
      equivalent to that of the bound phenol extract (47%). In addition, the planting
      environment exerts a very important influence on the polyphenol composition,
      content and antioxidant activity of blue highland barley. The correlation
      analysis showed that 2,4-hydroxybenzoic acid and protocatechuic acid were the
      main contributors to the DPPH* and ABTS*+ free radical scavenging capacity in the
      free phenolic extract, while chlorogenic acid, vanillic acid, ferulic acid and
      quercetin were the main contributors to the free radical scavenging capacity in
      the bound phenol extract. The study results show that the blue highland barley
      grains have rich phenolic compounds and high antioxidant activity, as well as
      significant varietal differences. The free and bound phenolic extracts in the
      blue hulless barley grains have an equivalent proportion in the total phenol, and
      co-exist in two forms. They can be used as a potential valuable source of natural
      antioxidants, and can aid in enhancing the development and daily consumption of
      foods relating to blue highland barley.

PMID- 29641471
TI  - Current's Fluctuations through Molecular Wires Composed of Thiophene Rings.
AB  - We study theoretically the electronic transport and quantum fluctuations in
      single-molecule systems using thiophene rings as integrated elementary functions,
      as well as the dependence of these properties with the increase of the coupled
      rings, i.e., as a quantum wire. In order to analyze the current flow through
      these molecular systems, the thiophene rings are considered to be connected to
      metal contacts, which, in general terms, will be related to the application of
      voltages (bias voltages or gate voltages) to generate non-equilibrium behavior
      between the contacts. Due to the nonlinear behavior that is generated when said
      voltages are applied, it is possible to observe quantum fluctuations in the
      transport properties of these molecular wires. For the calculation of the
      transport properties, we applied a tight-binding approach using the Landauer
      Buttiker formalism and the Fischer-Lee relationship, by means of a semi-analytic
      Green's function method within a real-space renormalization (decimation
      procedure). Our results showed an excellent agreement with results using a tight
      binding model with a minimal number of parameters reported so far for these
      molecular systems.

PMID- 29641470
TI  - Systematic Analysis of the Pleurotus ostreatus Laccase Gene (PoLac) Family and
      Functional Characterization of PoLac2 Involved in the Degradation of Cotton-Straw
      Lignin.
AB  - Fungal laccases play important roles in the degradation of lignocellulose.
      Although some PoLacs have been reported in several studies, still no
      comprehensive bioinformatics study of the LAC family in Pleurotus ostreatus has
      been reported. In this study, we identified 12 laccase genes in the whole genome
      sequence of P. ostreatus and their physical characteristics, gene distribution,
      phylogenic relationships, gene structure, conserved motifs, and cis-elements were
      also analyzed. The expression patterns of 12 PoLac genes at different
      developmental stages and under different culture substrates were also analyzed.
      The results revealed that PoLac2 and PoLac12 may be involved in the degradation
      of lignin and the formation of the fruiting body, respectively. Subsequently, we
      overexpressed PoLac2 in P. ostreatus by the Agrobacterium tumefaciens-mediated
      transformation (ATMT) method. The transformants' laccase activity increased in
      varying degrees, and the gene expression level of PoLac2 in transformants was 2-8
      times higher than that of the wild-type strain. Furthermore, the lignin
      degradation rate by transgenic fungus over 30 days was 2.36-6.3% higher than that
      of wild-type. Our data show that overexpression of PoLac2 significantly enhanced
      the lignin degradation of cotton-straw. To our knowledge, this study is the first
      report to demonstrate the functions of PoLac2 in P. ostreatus.

PMID- 29641472
TI  - Tracing Actin Filament Bundles in Three-Dimensional Electron Tomography Density
      Maps of Hair Cell Stereocilia.
AB  - Cryo-electron tomography (cryo-ET) is a powerful method of visualizing the three
      dimensional organization of supramolecular complexes, such as the cytoskeleton,
      in their native cell and tissue contexts. Due to its minimal electron dose and
      reconstruction artifacts arising from the missing wedge during data collection,
      cryo-ET typically results in noisy density maps that display anisotropic XY
      versus Z resolution. Molecular crowding further exacerbates the challenge of
      automatically detecting supramolecular complexes, such as the actin bundle in
      hair cell stereocilia. Stereocilia are pivotal to the mechanoelectrical
      transduction process in inner ear sensory epithelial hair cells. Given the
      complexity and dense arrangement of actin bundles, traditional approaches to
      filament detection and tracing have failed in these cases. In this study, we
      introduce BundleTrac, an effective method to trace hundreds of filaments in a
      bundle. A comparison between BundleTrac and manually tracing the actin filaments
      in a stereocilium showed that BundleTrac accurately built 326 of 330 filaments
      (98.8%), with an overall cross-distance of 1.3 voxels for the 330 filaments.
      BundleTrac is an effective semi-automatic modeling approach in which a seed point
      is provided for each filament and the rest of the filament is computationally
      identified. We also demonstrate the potential of a denoising method that uses a
      polynomial regression to address the resolution and high-noise anisotropic
      environment of the density map.

PMID- 29641473
TI  - Preconcentration of Trace Neonicotinoid Insecticide Residues Using Vortex
      Assisted Dispersive Micro Solid-Phase Extraction with Montmorillonite as an
      Efficient Sorbent.
AB  - In this work, we investigated montmorillonite for adsorption of neonicotinoid
      insecticides in vortex-assisted dispersive micro-solid phase extraction (VA-d-MU
      SPE). High-performance liquid chromatography with photodiode array detection was
      used for quantification and determination of neonicotinoid insecticide residues,
      including thiamethoxam, clothianidin, imidacloprid, acetamiprid, and thiacloprid.
      In this method, the solid sorbent was dispersed into the aqueous sample solution
      and vortex agitation was performed to accelerate the extraction process. Finally,
      the solution was filtered from the solid sorbent with a membrane filter. The
      parameters affecting the extraction efficiency of the proposed method were
      optimized, such as amount of sorbent, sample volume, salt addition, type and
      volume of extraction solvent, and vortex time. The adsorbing results show that
      montmorillonite could be reused at least 4 times and be used as an effective
      adsorbent for rapid extraction/preconcentration of neonicotinoid insecticide
      residues. Under optimum conditions, linear dynamic ranges were achieved between
      0.5 and 1000 ng mL-1 with a correlation of determination (R2) greater than 0.99.
      Limit of detection (LOD) ranged from 0.005 to 0.065 ng mL-1, while limit of
      quantification (LOQ) ranged from 0.008 to 0.263 ng mL-1. The enrichment factor
      (EF) ranged from 8 to 176-fold. The results demonstrated that the proposed method
      not only provided a more simple and sensitive method, but also can be used as a
      powerful alternative method for the simultaneous determination of insecticide
      residues in natural surface water and fruit juice samples.

PMID- 29641474
TI  - Application of High-Performance Liquid Chromatography Coupled with Linear Ion
      Trap Quadrupole Orbitrap Mass Spectrometry for Qualitative and Quantitative
      Assessment of Shejin-Liyan Granule Supplements.
AB  - A method for high-performance liquid chromatography coupled with linear ion trap
      quadrupole Orbitrap high-resolution mass spectrometry (HPLC-LTQ-Orbitrap MS) was
      developed and validated for the qualitative and quantitative assessment of Shejin
      liyan Granule. According to the fragmentation mechanism and high-resolution MS
      data, 54 compounds, including fourteen isoflavones, eleven ligands, eight
      flavonoids, six physalins, six organic acids, four triterpenoid saponins, two
      xanthones, two alkaloids, and one licorice coumarin, were identified or
      tentatively characterized. In addition, ten of the representative compounds
      (matrine, galuteolin, tectoridin, iridin, arctiin, tectorigenin, glycyrrhizic
      acid, irigenin, arctigenin, and irisflorentin) were quantified using the
      validated HPLC-LTQ-Orbitrap MS method. The method validation showed a good
      linearity with coefficients of determination (r2) above 0.9914 for all analytes.
      The accuracy of the intra- and inter-day variation of the investigated compounds
      was 95.0-105.0%, and the precision values were less than 4.89%. The mean
      recoveries and reproducibilities of each analyte were 95.1-104.8%, with relative
      standard deviations below 4.91%. The method successfully quantified the ten
      compounds in Shejin-liyan Granule, and the results show that the method is
      accurate, sensitive, and reliable.

PMID- 29641475
TI  - Novel Calcium Zirconate Silicate Cement Biomineralize and Seal Root Canals.
AB  - This study evaluated the sealing ability of gutta-percha (GP) with a calcium
      silicate-based sealer and a novel calcium zirconate containing calcium silicate
      cement (ZC). The root canals of the extracted premolars were prepared, which were
      then randomly allocated to three experimental groups (12 root canals per group)
      for obturation by continuous wave of condensation with the GP and AH 26 sealer
      (CW); obturation using a single GP with a calcium silicate-based EndoSequence BC
      sealer (SC); or obturation with ZC. The roots were inserted into sterile
      Eppendorf tubes, which were inoculated coronally with Porphyromonas gingivalis.
      The amount of endotoxin leakage into the apical reservoirs were measured using
      the Limulus Amebocyte Lysate (LAL) assay over 21 days, with comparisons made
      using one-way ANOVA and Scheffe's tests (alpha = 0.05). After 21 days, 75% of the
      canals that had been obturated by SC, 50% of those obturated by CW and 42% of
      those obturated by ZC showed endotoxin leakage. The amount of leakage was higher
      in the SC canals than in the CW (p = 0.031) or ZC (p = 0.03) canals, although
      there was no significant difference in the amount of leakage for CW and ZC (p >
      0.05). X-ray diffraction revealed the presence of tricalcium silicate (Ca3SiO5)
      and calcium zirconate (CaZrO3) in the synthesized ZC. Scanning electron
      microscopy revealed mineralized precipitates on the dentin of canals obturated by
      ZC. The novel calcium zirconate silicate cement appears to promote
      biomineralization and seal root canals at least as effectively as the
      conventional sealer.

PMID- 29641476
TI  - UiO-66-NH2/GO Composite: Synthesis, Characterization and CO2 Adsorption
      Performance.
AB  - In this work, a new composite materials of graphene oxide (GO)-incorporated metal
      organic framework (MOF)(UiO-66-NH2/GO) were in-situ synthesized, and were found
      to exhibit enhanced high performances for CO2 capture. X-ray diffraction (XRD),
      scanning electron microscope (SEM), N2 physical adsorption, and thermogravimetric
      analysis (TGA) were applied to investigate the crystalline structure, pore
      structure, thermal stability, and the exterior morphology of the composite. We
      aimed to investigate the influence of the introduction of GO on the stability of
      the crystal skeleton and pore structure. Water, acid, and alkali resistances were
      tested for physical and chemical properties of the new composites. CO2 adsorption
      isotherms of UiO-66, UiO-66-NH2, UiO-66/GO, and UiO-66-NH2/GO were measured at
      273 K, 298 K, and 318 K. The composite UiO-66-NH2/GO exhibited better optimized
      CO2 uptake of 6.41 mmol/g at 273 K, which was 5.1% higher than that of UiO-66/GO
      (6.10 mmol/g). CO2 adsorption heat and CO2/N2 selectivity were then calculated to
      further evaluate the CO2 adsorption performance. The results indicated that UiO
      66-NH2/GO composites have a potential application in CO2 capture technologies to
      alleviate the increase in temperature of the earth's atmosphere.

PMID- 29641477
TI  - The Influence of Different Metal Ions on the Absorption Properties of Nano-Nickel
      Zinc Ferrite.
AB  - The hydrothermal method was used to dope different amounts of Co2+, Mn2+, and
      Cu2+ in nano-nickel zinc ferrite powder. X-ray diffraction (XRD), a scanning
      electron microscopy (TEM), and a vector network analyzer (VNA) were used to
      explore the influence of doping on particle size, morphology, and electromagnetic
      wave absorption performance. Pure nanometer cobalt nickel zinc ferrite phase was
      prepared using the hydrothermal method with an increasing Co2+ content. Results
      showed that the grain type structure changed from a spherical structure to an
      irregular quadrilateral structure with the average particle size increasing from
      35 nm to 60 nm. The lattice constant increased from 0.8352 to 0.8404 nm with Co2+
      doping. The increasing Co2+ can change the position of the absorption peak,
      increase the bandwidth of the absorber, and improve the performance of the
      materials in GHz low frequency. The doping ratio of Mn2+ can affect the size of
      the lattice constant, but nanocrystals are easy to reunite without improving the
      electromagnetic loss. However, the absorbance performance decreases. For the
      doping of Cu2+, there is an agglomeration phenomenon. When the doping quantity is
      0.15, the absorbing wave performance becomes better.

PMID- 29641479
TI  - High Dynamic Range Imaging at the Quantum Limit with Single Photon Avalanche
      Diode-Based Image Sensors.
AB  - This paper examines methods to best exploit the High Dynamic Range (HDR) of the
      single photon avalanche diode (SPAD) in a high fill-factor HDR photon counting
      pixel that is scalable to megapixel arrays. The proposed method combines multi
      exposure HDR with temporal oversampling in-pixel. We present a silicon
      demonstration IC with 96 * 40 array of 8.25 um pitch 66% fill-factor SPAD-based
      pixels achieving >100 dB dynamic range with 3 back-to-back exposures (short, mid,
      long). Each pixel sums 15 bit-planes or binary field images internally to
      constitute one frame providing 3.75* data compression, hence the 1k frames per
      second (FPS) output off-chip represents 45,000 individual field images per second
      on chip. Two future projections of this work are described: scaling SPAD-based
      image sensors to HDR 1 MPixel formats and shrinking the pixel pitch to 1-3 um.

PMID- 29641478
TI  - Conflicting Roles of Connexin43 in Tumor Invasion and Growth in the Central
      Nervous System.
AB  - The tumor microenvironment is known to have increased levels of cytokines and
      metabolites, such as glutamate, due to their release from the surrounding cells.
      A normal cell around the tumor that responds to the inflammatory environment is
      likely to be subsequently altered. We discuss how these abnormalities will
      support tumor survival via the actions of gap junctions (GJs) and hemichannels
      (HCs) which are composed of hexamer of connexin43 (Cx43) protein. In particular,
      we discuss how GJ intercellular communication (GJIC) in glioma cells, the primary
      brain tumor, is a regulatory factor and its attenuation leads to tumor invasion.
      In contrast, the astrocytes, which are normal cells around the glioma, are
      "hijacked" by tumor cells, either by receiving the transmission of malignant
      substances from the cancer cells via GJIC, or perhaps via astrocytic HC activity
      through the paracrine signaling which enable the delivery of these substances to
      the distal astrocytes. This astrocytic signaling would promote tumor expansion in
      the brain. In addition, brain metastasis from peripheral tissues has also been
      known to be facilitated by GJs formed between cerebral vascular endothelial cells
      and cancer cells. Astrocytes and microglia are generally thought to eliminate
      cancer cells at the blood-brain barrier. In contrast, some reports suggest they
      facilitate tumor progression as tumor cells take advantage of the normal
      functions of astrocytes that support the survival of the neurons by exchanging
      nutrients and metabolites. In summary, GJIC is essential for the normal
      physiological function of growth and allowing the diffusion of physiological
      substances. Therefore, whether GJIC is cancer promoting or suppressing may be
      dependent on what permeates through GJs, when it is active, and to which cells.
      The nature of GJs, which has been ambiguous in brain tumor progression, needs to
      be revisited and understood together with new findings on Cx proteins and HC
      activities.

PMID- 29641481
TI  - A Novel Well Drill Assisted with High-Frequency Vibration Using the Bending Mode.
AB  - It is important for companies to increase the efficiency of drilling as well as
      prolong the lifetime of the drilling tool. Since some previous investigations
      indicated that a superposition of well drilling with an additional vibration
      increases the drilling efficiency, this paper introduces a novel well drill which
      is assisted with additional vibrations by means of piezoelectric sandwich bending
      vibration transducer. The proposed drill uses bending vibrations in two different
      directions to from an elliptical trajectory movement, which can help the drill to
      break the surface of hard material more efficiently and clean away the lithic
      fragments more easily. The proposed well drill with bending vibration transducer
      is designed to have a resonance frequency of the first bending vibration mode of
      about 1779 Hz. The motion equation of the particle on the edge of the drill bit
      is developed and analyzed. The vibration trajectory of the particle on the edge
      of the drill bit is calculated by using finite element method. A prototype of the
      proposed drill using bending vibrations is fabricated and tested to verify the
      aim of drilling efficiency increase. The feed speed of the vibration assisted
      drilling is tested to be about 0.296 mm/s when the excitation voltage of the
      transducer is 300 V, while this speed decreases to about 0.195 mm/s when no
      vibration is added. This comparison shows that the feed speed of the vibration
      assisted drilling is about 52% higher than that of the normal drilling, which
      means the proposed drill has a better efficiency and it is important to consider
      vibration superimposition in well drilling. In addition, the surface of the drill
      hole gained by the vibration assisted drilling is smoother than that of the
      normal drilling, which makes the clearance easier.

PMID- 29641480
TI  - Friday Night Is Pizza Night: A Comparison of Children's Dietary Intake and
      Maternal Perceptions and Feeding Goals on Weekdays and Weekends.
AB  - Childhood obesity is a serious issue in the U.S. While obesity is the result of a
      multitude of factors, a great deal of research has focused on children's dietary
      intake. While children's eating patterns vary throughout the week, not much else
      is known about weekday-weekend differences. Therefore, the current study examined
      differences in the frequency and portion size of school-age children's
      consumption of common foods and beverages, as well as mothers' perceptions of
      those items and their child feeding goals, on weekdays and weekends. A total of
      192 mothers of children aged 7 to 11 were recruited through Amazon's Mechanical
      Turk. Results showed a consistent pattern of more frequent consumption and larger
      portions of unhealthy foods and beverages on weekends. This aligned with mothers'
      perceptions of those foods and beverages as weekend items, as well as their
      feeding goals of health and price being less important on weekends. It is quite
      possible that weekends are viewed as having less structure and facilitate
      schedules that allow children to consume more meals away from home. These
      findings shed light on additional risk factors in children's eating patterns and
      highlight the serious implications that day of the week can have on childhood
      obesity.

PMID- 29641482
TI  - Phase-Shifted Eccentric Core Fiber Bragg Grating Fabricated by Electric Arc
      Discharge for Directional Bending Measurement.
AB  - A phase-shifted eccentric core fiber Bragg grating (PS-ECFBG) fabricated by
      electric arc discharge (EAD) is presented and demonstrated. It is composed of a
      fraction of eccentric core fiber fusion spliced in between two pieces of
      commercial single mode fibers, where a PS-FBG was written. The EAD in this work
      could flexibly change the amount of phase-shift by changing the discharge number
      or discharge duration. Because of the offset location of the eccentric core and
      the ultra-narrow resonant peak of the PS-ECFBG, it has a higher accuracy for
      measuring the directional bend. The elongation and compression of the eccentric
      core keep the magnitude of phase shift still unchanged during the bending
      process. The bending sensitivities of the PS-ECFBG at two opposite most sensitive
      directions are 57.4 pm/m-1 and -51.5 pm/m-1, respectively. Besides, the PS-ECFBG
      has the potential to be a tunable narrow bandpass filter, which has a wider bi
      directional adjustable range because of the bending responses. The strain and
      temperature sensitivities of the PS-ECFBG are experimentally measured as well,
      which are 0.70 pm/MUepsilon and 8.85 pm/ degrees C, respectively.

PMID- 29641483
TI  - Effects of Mind-Body Exercises for Mood and Functional Capabilities in Patients
      with Stroke: An Analytical Review of Randomized Controlled Trials.
AB  - Objective: The effects of stroke are both physical and mental in nature and may
      have serious implications on the overall well-being of stroke survivors. This
      analytical review aims to critically evaluate and statistically synthesize the
      existing literature regarding the effects of mind-body (MB) exercises on mood and
      functional capabilities in patients with stroke. Methods: A structured literature
      review was performed in both English (PubMed, PEDro, and Cochrane Library) and
      Chinese (Wanfang and CNKI (Chinese National Knowledge Information Database))
      databases. Sixteen randomized controlled trials were considered eligible for meta
      analysis. Based on the random effects model, we used the pooled effect size to
      determine the magnitude of rehabilitative effect of MB exercise intervention on
      depression, anxiety, activities of daily living, and functional mobility among
      stroke survivors. The sum PEDro score ranged from five to nine points (fair-to
      good methodological quality), but the absence of concealed allocation and blinded
      assessors were reported in most studies. Results: The aggregated results showed
      that MB exercise intervention is associated with significantly improved ADL
      (Hedges' g = 1.31, 95% CI 0.85 to 1.77, p < 0.001, I2 = 79.82%) and mobility
      (Hedges' g = 0.67, 95% CI 0.25 to 1.09, p < 0.001, I2 = 69.65%), and reduced
      depression (Hedges' g = -0.76, 95% CI -1.16 to -0.35, p < 0.001, I2 = 74.84%).
      Conclusions: as add-on treatments, the MB exercises may potentially improve
      depression, activities of daily living, and mobility of these post-stroke
      patients. Future studies with more robust methodology will be needed to provide a
      more definitive conclusion.

PMID- 29641484
TI  - An Overview on the Clinical Development of Tau-Based Therapeutics.
AB  - Tauopathies such as Alzheimer's disease (AD), frontotemporal lobar degeneration,
      or progressive supranuclear palsy constitute a group of brain disorders defined
      by neurodegeneration and the presence of tau aggregates in the affected brains
      regions. Tau is a microtubule-associated protein that accumulates in the cytosol
      under pathological conditions, steering the formation of aggregates or inclusions
      thought to be involved in the degeneration and neuronal death associated with
      these diseases. Despite a substantial and unmet medical need for novel, more
      effective disease-modifying therapies for the treatment of AD and tauopathies,
      the last couple of decades have seen numerous drug development undertakings
      primarily focused on beta-amyloid, with disappointing results to date. On the
      other hand, tau-focused approaches have not received much attention until
      recently, notwithstanding that the presence of extensive tau pathology is
      fundamental for the disease and tau pathology shows a better correlation with
      impaired cognitive function than with amyloid pathology in AD patients. The last
      few years have brought us advances in our comprehension of tau biological
      functions beyond its well-established role as a microtubule-associated protein,
      unveiling novel physiological tau functions that may also be involved in
      pathogenesis and thus provide novel targets for therapeutic intervention. This
      review describes several emerging, encouraging therapeutic approaches aimed at
      tackling the underlying causes of tau pathology in AD and other tauopathies that
      have recently reached the clinical development stage.

PMID- 29641485
TI  - Factors Related to Unemployment in Europe. A Cross-Sectional Study from the
      COURAGE Survey in Finland, Poland and Spain.
AB  - Background: Research addressing the impact of a large number of factors on
      unemployment is scarce. We aimed to comprehensively identify factors related to
      unemployment in a sample of persons aged 18-64 from Finland, Poland and Spain.
      Methods: In this cross-sectional study, factors from different areas were
      considered: socio-demographic indicators, health habits, chronic conditions,
      health state markers, vision and hearing indicators, and social networks and
      built environment scores. Results: Complete data were available for 5003
      participants, mean age 48.1 (SD 11.5), 45.4% males. The most important factors
      connected to unemployment were health status indicators such as physical
      disability (OR = 2.944), self-rated health (OR = 2.629), inpatient care (OR =
      1.980), and difficulties with getting to the toilet (OR = 2.040), while the most
      relevant factor related to employment were moderate alcohol consumption (OR =
      0.732 for non-heavy drinkers; OR = 0.573 for infrequent heavy drinkers), and
      being married (OR = 0.734), or having been married (OR = 0.584). Other factors
      that played a significant role included presence of depression (OR = 1.384) and
      difficulties with near vision (OR = 1.584) and conversation hearing (OR = 1.597).
      Conclusions: Our results highlight the importance of selected factors related to
      unemployment, and suggest public health indications that could support concrete
      actions on modifiable factors, such as those aimed to promote physical activity
      and healthy behaviors, tackling depression or promoting education, in particular
      for the younger.

PMID- 29641486
TI  - Opposing Roles of Calcium and Intracellular ATP on Gating of the Purinergic P2X2
      Receptor Channel.
AB  - P2X2 receptors (P2X2R) exhibit a slow desensitization during the initial ATP
      application and a progressive, calcium-dependent increase in rates of
      desensitization during repetitive stimulation. This pattern is observed in whole
      cell recordings from cells expressing recombinant and native P2X2R. However,
      desensitization is not observed in perforated-patched cells and in two-electrode
      voltage clamped oocytes. Addition of ATP, but not ATPgammaS or GTP, in the
      pipette solution also abolishes progressive desensitization, whereas
      intracellular injection of apyrase facilitates receptor desensitization.
      Experiments with injection of alkaline phosphatase or addition of staurosporine
      and ATP in the intracellular solution suggest a role for a phosphorylation
      dephosphorylation in receptor desensitization. Mutation of residues that are
      potential phosphorylation sites identified a critical role of the S363 residue in
      the intracellular ATP action. These findings indicate that intracellular calcium
      and ATP have opposing effects on P2X2R gating: calcium allosterically facilitates
      receptor desensitization and ATP covalently prevents the action of calcium.
      Single cell measurements further revealed that intracellular calcium stays
      elevated after washout in P2X2R-expressing cells and the blockade of
      mitochondrial sodium/calcium exchanger lowers calcium concentrations during
      washout periods to basal levels, suggesting a role of mitochondria in this
      process. Therefore, the metabolic state of the cell can influence P2X2R gating.

PMID- 29641487
TI  - Concerns about Quadrupole ICP-MS Lead Isotopic Data and Interpretations in the
      Environment and Health Fields.
AB  - There has been a massive increase in recent years of the use of lead (Pb)
      isotopes in attempts to better understand sources and pathways of Pb in the
      environment and in man or experimental animals. Unfortunately, there have been
      many cases where the quality of the isotopic data, especially that obtained by
      quadrupole inductively coupled plasma mass spectrometry (Q-ICP-MS), are
      questionable, resulting in questionable identification of potential sources,
      which, in turn, impacts study interpretation and conclusions. We present several
      cases where the isotopic data have compromised interpretation because of the use
      of only the major isotopes 208Pb/206Pb and 207Pb/206Pb, or their graphing in
      other combinations. We also present some examples comparing high precision data
      from thermal ionization (TIMS) or multi-collector plasma mass spectrometry (MC
      ICP-MS) to illustrate the deficiency in the Q-ICP-MS data. In addition, we
      present cases where Pb isotopic ratios measured on Q-ICP-MS are virtually
      impossible for terrestrial samples. We also evaluate the Pb isotopic data for rat
      studies, which had concluded that Pb isotopic fractionation occurs between
      different organs and suggest that this notion of biological fractionation of Pb
      as an explanation for isotopic differences is not valid. Overall, the brief
      review of these case studies shows that Q-ICP-MS as commonly practiced is not a
      suitable technique for precise and accurate Pb isotopic analysis in the
      environment and health fields.

PMID- 29641488
TI  - CA 19-9 Pancreatic Tumor Marker Fluorescence Immunosensing Detection via
      Immobilized Carbon Quantum Dots Conjugated Gold Nanocomposite.
AB  - The clinical detection of carbohydrate antigen 19-9 (CA 19-9), a tumor marker in
      biological samples, improves and facilitates the rapid screening and diagnosis of
      pancreatic cancer. A simple, low cost, fast, and green synthesis method to
      prepare a viable carbon quantum dots/gold (CQDs/Au) nanocomposite fluorescence
      immunosensing solution for the detection of CA 19-9 was reported. The present
      method is conducted by preparing glucose-derived CQDs using a microwave-assisted
      method. CQDs were employed as reducing and stabilizing agents for the preparation
      of a CQDs/Au nanocomposite. The immobilized anti-CA 19-9-labeled horseradish
      peroxidase enzyme (Ab-HRP) was anchored to the surface of a CQDs/Au nanocomposite
      by a peptide interaction between the carboxylic and amine active groups. The CA
      19-9 antigen was trapped by another monoclonal antibody that was coated on the
      surface of microtiter wells. The formed sandwich capping antibody-antigen
      antibody enzyme complex had tunable fluorescence properties that were detected
      under excitation and emission wavelengths of 420 and 530 nm. The increase in
      fluorescence intensities of the immunoassay sensing solution was proportional to
      the CA 19-9 antigen concentration in the linear range of 0.01-350 U mL-1 and had
      a lower detection limit of 0.007 U mL-1. The proposed CQDs/Au nanocomposite
      immunoassay method provides a promising tool for detecting CA 19-9 in human
      serum.

PMID- 29641490
TI  - Effect of Atmospheric Corrosion on the Mechanical Properties of SAE 1020
      Structural Steel.
AB  - Resistance to atmospheric corrosion in different environments located in Chile
      and the corrosion's effect on the mechanical properties of SAE 1020 steel were
      studied. Atmospheric corrosivity categories at each station under study were
      determined. These categories were C2, for Laja; C3 and C4, for the Arica and
      Antarctic stations, respectively; and the most aggressive, C5 and higher at
      Quintero. These specific environments significantly influenced the mechanical
      responses of steel exposed for 36 months. Rupture elongation, the modulus of
      toughness, ultimate tensile strength, and hardness of the material all decreased
      as a function of environmental atmospheric aggressiveness. Lowered ductility is
      the result of the increased corrosion rate due to the high deposition of
      chlorides. This is due to the morphology of material degradation, which
      consequently occurs as pores, microstrains, and other defects that promote early
      rupture of the steel.

PMID- 29641489
TI  - Non-Coding Transcript Heterogeneity in Mesothelioma: Insights from Asbestos
      Exposed Mice.
AB  - Mesothelioma is an aggressive, rapidly fatal cancer and a better understanding of
      its molecular heterogeneity may help with making more efficient therapeutic
      strategies. Non-coding RNAs represent a larger part of the transcriptome but
      their contribution to diseases is not fully understood yet. We used recently
      obtained RNA-seq data from asbestos-exposed mice and performed data mining of
      publicly available datasets in order to evaluate how non-coding RNA contribute to
      mesothelioma heterogeneity. Nine non-coding RNAs are specifically elevated in
      mesothelioma tumors and contribute to human mesothelioma heterogeneity. Because
      some of them have known oncogenic properties, this study supports the concept of
      non-coding RNAs as cancer progenitor genes.

PMID- 29641491
TI  - Rapidly-Dissolving Silver-Containing Bioactive Glasses for Cariostatic
      Applications.
AB  - A novel bioactive glass series containing incremental amounts of silver oxide was
      synthesized, ground down, and subsequently incorporated into a dentifrice for the
      purpose of reducing the incidence of dental caries and lesion formation. Three
      glasses were synthesized using the melt quench route: Si-Control (70SiO2-12CaO
      3P2O5-15Na2O, mol %), Si-02 and Si-05, where 0.2 and 0.5 mol % Ag2O were
      substituted, respectively, for SiO2 in Si-Control. The glasses were then ground,
      sieved, characterized, and dissolved in Tris buffer solution (pH = 7.30) for 6,
      12, and 24 h, with the pH of the resultant solution being recorded and the ions
      that were released into solution quantified. Samples of each glass were
      subsequently embedded into a non-fluoridated, commercially available toothpaste
      which was then used to brush resin-mounted lamb molars which, up to the point of
      testing, had been stored in a 1.0 M HCl solution. Knoop microhardness
      measurements of the molars were recorded before and after brushing to determine
      the presence of remineralization on the surface of the teeth (surface hardness
      loss of 37%, 35%, and 34% for Si-Control, Si-02 and Si-05, respectively, after 24
      h). Four oral cavity bacterial strains were isolated through swabs of the inner
      cheek, gums, and teeth surfaces of three volunteers, and placed on agar discs. Of
      each glass, 0.5 g was placed onto the discs, and the resultant inhibition zones
      were measured after 6, 12, and 24 h. Si-05 performed better than Si-02 on two
      strains after 24 h, while exhibiting similar behavior for the remaining two
      strains after 24 h; the largest inhibition zone measured was 2.8 mm, for Si-05
      after 12 h. Si-Control exhibited no antibacterial effect at any time point,
      providing evidence for the role of silver oxide as the antibacterial component of
      these glasses.

PMID- 29641493
TI  - Comparison of the Effect of Toothbrushing Education Via Video, Lecture and
      Pamphlet on the Dental Plaque Index of 12-Year-Old Children.
AB  - The aim of this study was to compare the effect of different modes of
      toothbrushing education (lecture, video and pamphlet) on the dental plaque index
      (PI) of adolescents. The cluster randomized intervention was performed on 128
      participants aged 12 years, who were allocated into four groups based on the type
      of intervention. Group 1: no intervention; and groups 2, 3, 4: education via
      lecture, video, and pamphlet, respectively (n = 32). Their plaque index was
      measured at the baseline, 24 h and two months later. Data were analyzed by
      repeated measures analysis of variance (ANOVA), one-way ANOVA, independent and
      paired t-test. The plaque indices of groups 2, 3, 4 at 24 h (p values < 0.001)
      and two months (p values < 0.001) showed a significant reduction when compared to
      the baseline. The lowest PI score was observed in the pamphlet, video and lecture
      groups at 24 h, respectively. After 2 months, the lowest score of PI was measured
      in lecture, video and pamphlet groups, respectively; however, these differences
      were non-significant. Therefore, toothbrushing education via lecture, video and
      pamphlet reduced the dental plaque index with the same effectiveness.

PMID- 29641494
TI  - Maternal Melatonin Therapy Attenuated Maternal High-Fructose Combined with Post
      Weaning High-Salt Diets-Induced Hypertension in Adult Male Rat Offspring.
AB  - Consumption of food high in fructose and salt is associated with the epidemic of
      hypertension. Hypertension can originate from early life. Melatonin, a
      pleiotropic hormone, regulates blood pressure. We examined whether maternal
      melatonin therapy can prevent maternal high-fructose combined with post-weaning
      high-salt diet-induced programmed hypertension in adult offspring. Pregnant
      Sprague-Dawley rats received either a normal diet (ND) or a 60% fructose diet
      (HF) during pregnancy and the lactation period. Male offspring were on either the
      ND or a high-salt diet (HS, 1% NaCl) from weaning to 12 weeks of age and were
      assigned to five groups (n = 8/group): ND/ND, HF/ND, ND/HS, HF/HS, and
      HF/HS+melatonin. Melatonin (0.01% in drinking water) was administered during
      pregnancy and lactation. We observed that maternal HF combined with post-weaning
      HS diets induced hypertension in male adult offspring, which was attenuated by
      maternal melatonin therapy. The beneficial effects of maternal melatonin therapy
      on HF/HS-induced hypertension related to regulating several nutrient-sensing
      signals, including Sirt1, Sirt4, Prkaa2, Prkab2, Pparg, and Ppargc1a.
      Additionally, melatonin increased protein levels of mammalian targets of
      rapamycin (mTOR), decreased plasma asymmetric dimethylarginine (ADMA) and
      symmetric dimethylarginine levels, and increased the l-arginine-to-ADMA ratio.
      The reprogramming effects by which maternal melatonin therapy protects against
      hypertension of developmental origin awaits further elucidation.

PMID- 29641492
TI  - Latest Innovations in the Treatment of Venous Disease.
AB  - Venous disease is more common than peripheral arterial disease.
      Pathophysiologically, venous disease can be associated with obstruction, reflux,
      or both. A common feature in chronic venous disease is ambulatory venous
      hypertension. Inflammatory and pro-thrombotic mechanisms can be activated. The
      current therapies, including compression, ablation, and recanalization are
      discussed.

PMID- 29641495
TI  - Furan- and Thiophene-2-Carbonyl Amino Acid Derivatives Activate Hypoxia-Inducible
      Factor via Inhibition of Factor Inhibiting Hypoxia-Inducible Factor-1.
AB  - Induction of a series of anti-hypoxic proteins protects cells during exposure to
      hypoxic conditions. Hypoxia-inducible factor-alpha (HIF-alpha) is a major
      transcription factor that orchestrates this protective effect. To activate HIF
      exogenously, without exposing cells to hypoxic conditions, many small-molecule
      inhibitors targeting prolyl hydroxylase domain-containing protein have been
      developed. In addition, suppression of factor inhibiting HIF-1 (FIH-1) has also
      been shown to have the potential to activate HIF-alpha. However, few small
      molecule inhibitors of FIH-1 have been developed. In this study, we synthesized a
      series of furan- and thiophene-2-carbonyl amino acid derivatives having the
      potential to inhibit FIH-1. The inhibitory activities of these compounds were
      evaluated in SK-N-BE(2)c cells by measuring HIF response element (HRE) promoter
      activity. Several furan- and thiophene-2-carbonyl amino acid derivatives
      inhibited FIH-1 based on correlations among the docking score of the FIH-1 active
      site, the chemical structure of the compounds, and biological HIF-alpha/HRE
      transcriptional activity.

PMID- 29641496
TI  - The Structure of the Lipid A from the Halophilic Bacterium Spiribacter salinus
      M19-40T.
AB  - The study of the adaptation mechanisms that allow microorganisms to live and
      proliferate in an extreme habitat is a growing research field. Directly exposed
      to the external environment, lipopolysaccharides (LPS) from Gram-negative
      bacteria are of great appeal as they can present particular structural features
      that may aid the understanding of the adaptation processes. Moreover, through
      being involved in modulating the mammalian immune system response in a structure
      dependent fashion, the elucidation of the LPS structure can also be seen as a
      fundamental step from a biomedical point of view. In this paper, the lipid A
      structure of the LPS from Spiribacter salinus M19-40T, a halophilic gamma
      proteobacteria, was characterized through chemical analyses and matrix-assisted
      laser desorption ionization (MALDI) mass spectrometry. This revealed a mixture of
      mono- and bisphosphorylated penta- to tri-acylated species with the uncommon 2 +
      3 symmetry and bearing an unusual 3-oxotetradecaonic acid.

PMID- 29641497
TI  - Outcomes of Secondary Prevention among Coronary Heart Disease Patients in a High
      Risk Region in Finland.
AB  - Despite comprehensive national treatment guidelines, goals for secondary
      prevention of coronary heart disease (CHD) have not been sufficiently met
      everywhere in Finland. We investigated the recorded risk factor rates of CHD and
      their spatial differences in North Karelia Hospital District, which has a very
      high cardiovascular burden, in order to form a general view of the state of
      secondary prevention in a high-risk region. Appropriate disease codes of CHD
      diagnoses and coding for percutaneous coronary intervention (PCI) and coronary
      artery bypass grafting (CABG) were used to identify from the electronic patient
      records the patient group eligible for secondary prevention. The cumulative
      incidence rate of new patients (n = 2556) during 2011-2014 varied from 1.9% to
      3.5% between municipalities. The success in secondary prevention of CHD was
      assessed using achievement of treatment targets as defined in national
      guidelines. Health centres are administrated by municipalities whereupon the main
      reporting units were municipalities, together with composed classification of
      patients by age, gender and dwelling location. Health disparities between
      municipalities, settlement types and patient groups were found and are
      interpreted. Moreover, spatial high-risk and low-risk clusters of acute CHD were
      detected. The proportion of patients achieving the treatment targets of low
      density lipoprotein cholesterol (LDL-C) varied from 21% to 38% between
      municipalities. Variation was also observed in the follow-up of patients; e.g.,
      the rate of follow-up measurements of LDL-C in municipalities varied from 72% to
      86%. Spatial variation in patients' sociodemographic and neighbourhood
      characteristics and morbidity burden partly explain the differences in outcomes,
      but there are also very likely differences in the care process between
      municipalities which requires a study in its own right.

PMID- 29641498
TI  - A Novel Synthetic Material, BMM, Accelerates Wound Repair by Stimulating Re
      Epithelialization and Fibroblast Activation.
AB  - Cutaneous wound repair is an intricate process whereby the skin reprograms itself
      after injury. In the mid-phase of wound repair, the proliferation, migration, and
      differentiation of cells are the major mechanisms to lead remodeling. We
      investigated the effect of BMM ((1E,2E)-1,2-bis((6-bromo-2H-chromen-3
      yl)methylene)hydrazine), a novel synthetic material, on the migration and
      viability of keratinocytes or fibroblasts using the in vitro scratch
      woundhealing, electric cell-substrate imedance sensing (ECIS), invasion, and MTT
      assays. Cell migration-related factors were analyzed using western blot, and we
      found that treatment with BMM stimulated the EMT pathway and focal adhesion
      kinase (FAK)/Src signaling. Differentiation of HaCaT keratinocyte and fibroblast
      cells was also stimulated by BMM and specifically, NOX2/4 contributed to the
      activation of fibroblasts for wound healing. Furthermore, BMM treated HaCaT
      keratinocyte and fibroblast-co-cultured cells increased migration and
      differentiation. TGF-beta and Cyr61 were also secreted to a greater extent than
      in single cultured cells. In vivo experiments showed that treatment with BMM
      promotes wound closure by promoting re-epithelialization. In this study, we
      demonstrated that a novel synthetic material, BMM, is capable of promoting wound
      healing via the stimulation of re-epithelialization in the epidermis and the
      activation of fibroblasts in the dermis, in particular, via the acceleration of
      the interaction between the epidermis and dermis.

PMID- 29641499
TI  - Beneficial Phytochemicals with Anti-Tumor Potential Revealed through Metabolic
      Profiling of New Red Pigmented Lettuces (Lactuca sativa L.).
AB  - The present study aimed to compare polyphenols among red lettuce cultivars and
      identify suitable cultivars for the development and utilization of healthy
      vegetables. Polyphenols, mineral elements, and antioxidant activity were analyzed
      in the leaves of six red pigmented lettuce (Lactuca sativa L.) cultivars;
      thereafter, we assessed the anti-tumor effects of cultivar B-2, which displayed
      the highest antioxidant activity. Quadrupole-Orbitrap mass spectrometry analysis
      revealed four classes of polyphenols in these cultivars. The composition and
      contents of these metabolites varied significantly among cultivars and primarily
      depended on leaf color. The B-2 cultivar had the highest antioxidant potential
      than others because it contained the highest levels of polyphenols, especially
      anthocyanin, flavone, and phenolic acid; furthermore, this cultivar displayed
      anti-tumor effects against the human lung adenocarcinoma cell line A549, human
      hepatoma cell line Bel7402, human cancer colorectal adenoma cell line HCT-8, and
      HT-29 human colon cancer cell line. Hence, the new red-leaf lettuce cultivar B-2
      has a distinct metabolite profile, with high potential for development and
      utilization of natural phytochemical and mineral resources in lettuces and can be
      used as a nutrient-dense food product.

PMID- 29641500
TI  - A Spatial Panel Data Analysis of Economic Growth, Urbanization, and NOx Emissions
      in China.
AB  - Abstract: Is nitrogen oxides emissions spatially correlated in a Chinese context?
      What is the relationship between nitrogen oxides emission levels and fast-growing
      economy/urbanization? More importantly, what environmental preservation and
      economic developing policies should China's central and local governments take to
      mitigate the overall nitrogen oxides emissions and prevent severe air pollution
      at the provincial level in specific locations and their neighboring areas? The
      present study aims to tackle these issues. This is the first research that
      simultaneously studies the nexus between nitrogen oxides emissions and economic
      development/urbanization, with the application of a spatial panel data technique.
      Our empirical findings suggest that spatial dependence of nitrogen oxides
      emissions distribution exists at the provincial level. Through the investigation
      of the existence of an environmental Kuznets curve (EKC) embedded within the
      Stochastic Impacts by Regression on Population, Affluence, and Technology
      (STIRPAT) framework, we conclude something interesting: an inverse N-shaped EKC
      describes both the income-nitrogen oxides nexus and the urbanization-nitrogen
      oxides nexus. Some well-directed policy advice is provided to reduce nitrogen
      oxides in the future. Moreover, these results contribute to the literature on
      development and pollution.

PMID- 29641502
TI  - Determinants and the Moderating Effect of Perceived Policy Effectiveness on
      Residents' Separation Intention for Rural Household Solid Waste.
AB  - Currently, villages "besieged with garbage" have become a serious problem in
      rural areas of China. Separation of rural residential solid waste (RRSW) is one
      of the main strategies for waste reduction. Although previous studies have
      analyzed the social and psychological motivations of residents' separation
      intention for municipal solid waste (MSW), little attention has been paid to the
      situation in rural areas. This paper investigates key factors influencing rural
      residents' separation intention, as well as analyzing the moderating effects of
      perceived policy effectiveness on the relationship between the determinants and
      the intention, using survey data of 538 rural residents in the province of
      Sichuan in China. The results show that all the proposed key factors influence
      the separation intention significantly. Furthermore, the policies were divided
      into two types and the moderating effects were tested for each type. The results
      show that the perceived effectiveness of both the inducement policy and the
      capacity building policy moderated the relationship between attitude and
      separation intention positively, while the perceived effectiveness of the
      inducement policy moderated the relationship between subjective norms and
      intention negatively. The findings provide insightful information for
      policymakers to design effective RRSW separation policies.

PMID- 29641501
TI  - Zinc Protects Articular Chondrocytes through Changes in Nrf2-Mediated
      Antioxidants, Cytokines and Matrix Metalloproteinases.
AB  - Osteoarthritis (OA) is an age-related degenerative joint disease characterized by
      high oxidative stress, chondrocyte death and cartilage damage. Zinc has been
      implicated in the antioxidant capacity of the cell, and its deficiency might
      inhibit chondrocyte proliferation. The present study examined the potential of
      zinc as a preventive supplement against OA using the in vitro chondrosarcoma cell
      line SW1353 and an in vivo Wistar rat model to mimic OA progress induced by
      monosodium iodoacetate (MIA). The results demonstrated that, in SW1353 cells, 5
      MUM MIA exposure increased oxidative stress and decreased the expression of GPx1
      and Mn-SOD but still increased GSH levels and HO-1 expression and enhanced the
      expression of interleukin (IL)-10, IL-1beta, and matrix metalloproteinase (MMP)
      13. Zinc addition could block these changes. Besides, the expression of Nrf2 and
      phosphorylated (p)-Akt was dramatically increased, implicating the p-Akt/Nrf2
      pathway in the effects of zinc on MIA-treated cells. A rat model achieved similar
      results as those of cell culture, and 1.6 mg/kg/day of zinc supplementation is
      sufficient to prevent OA progress, while 8.0 mg/kg/day of zinc supplementation
      does not have a better effect. These findings indicate that zinc supplementation
      exerts a preventive effect with respect to MIA-induced OA progress.

PMID- 29641503
TI  - Alloying and Hardness of Eutectics with Nbss and Nb5Si3 in Nb-silicide Based
      Alloys.
AB  - In Nb-silicide based alloys, eutectics can form that contain the Nbss and Nb5Si3
      phases. The Nb5Si3 can be rich or poor in Ti, the Nb can be substituted with
      other transition and refractory metals, and the Si can be substituted with simple
      metal and metalloid elements. For the production of directionally solidified in
      situ composites of multi-element Nb-silicide based alloys, data about eutectics
      with Nbss and Nb5Si3 is essential. In this paper, the alloying behaviour of
      eutectics observed in Nb-silicide based alloys was studied using the parameters
      DeltaHmix, DeltaSmix, VEC (valence electron concentration), delta (related to
      atomic size), Deltachi (related to electronegativity), and Omega (= Tm
      DeltaSmix/|DeltaHmix|). The values of these parameters were in the ranges -41.9 <
      DeltaHmix <-25.5 kJ/mol, 4.7 < DeltaSmix < 15 J/molK, 4.33 < VEC < 4.89, 6.23 <
      delta < 9.44, 0.38 < Omega < 1.35, and 0.118 < Deltachi < 0.248, with a gap in
      Deltachi values between 0.164 and 0.181. Correlations between DeltaSmix, Omega,
      DeltaSmix, and VEC were found for all of the eutectics. The correlation between
      DeltaHmix and delta for the eutectics was the same as that of the Nbss, with more
      negative DeltaHmix for the former. The delta versus Deltachi map separated the Ti
      rich eutectics from the Ti-poor eutectics, with a gap in Deltachi values between
      0.164 and 0.181, which is within the Deltachi gap of the Nbss. Eutectics were
      separated according to alloying additions in the Deltachi versus VEC, Deltachi
      versus <Si>, delta versus <Si>, and VEC versus <Si> maps, where <Si> = Al + Ge +
      Si + Sn. Convergence of data in maps occurred at delta ~ 9.25, VEC ~ 4.35,
      Deltachi in the range ~ 0.155 to 0.162, and <Si> in the range ~ 21.6 at.% to ~
      24.3 at.%. The convergence of data also indicated that the minimum concentration
      of Ti and maximum concentrations of Al and Si in the eutectic were about 8.7 at.%
      Ti, 6.3 at.% Al, and 21.6 at.% Si, respectively, and that the minimum
      concentration of Si in the eutectic was in the range 8 < Si < 10 at.%.

PMID- 29641504
TI  - Assessing Residential Exposure Risk from Spills of Flowback Water from Marcellus
      Shale Hydraulic Fracturing Activity.
AB  - Identifying sources of concern and risk from shale gas development, particularly
      from the hydraulic fracturing process, is an important step in better
      understanding sources of uncertainty within the industry. In this study, a risk
      assessment of residential exposure pathways to contaminated drinking water is
      carried out. In this model, it is assumed that a drinking water source is
      contaminated by a spill of flowback water; probability distributions of spill
      size and constituent concentrations are fit to historical datasets and Monte
      Carlo simulation was used to calculate a distribution of risk values for two
      scenarios: (1) use of a contaminated reservoir for residential drinking water
      supply and (2) swimming in a contaminated pond. The swimming scenario did not
      produce risks of concern from a single exposure of 1 h duration, but 11 such 1-h
      exposures did produce risks of 10-6 due to radionuclide exposure. The drinking
      water scenario over a 30-year exposure duration produced cancer risk values
      exceeding 10-6 for arsenic, benzene, benzo(a)pyrene, heptachlor, heptachlor
      epoxide, pentachlorophenol, and vinyl chloride. However, this extended exposure
      duration is probably not realistic for exposure by a spill event. Radionuclides
      produced risks in the residential drinking water scenario of 10-6 in just 8 h, a
      much more realistic timeline for continual exposure due to a spill event. In
      general, for contaminants for which inhalation exposure was applicable, this
      pathway produced the highest risks with exposure from ingestion posing the next
      greatest risk to human health followed by dermal absorption (or body emersion for
      radionuclides). Considering non-carcinogenic effects, only barium and thallium
      exceed target limits, where the ingestion pathway seems to be of greater concern
      than dermal exposure. Exposure to radionuclides in flowback water, particularly
      through the inhalation route, poses a greater threat to human health than other
      contaminants examined in this assessment and should be the focus of risk
      assessment and risk mitigation efforts.

PMID- 29641505
TI  - Infrared and Visible Image Fusion Based on Different Constraints in the Non
      Subsampled Shearlet Transform Domain.
AB  - There are many artificial parameters when fuse infrared and visible images, to
      overcome the lack of detail in the fusion image because of the artifacts, a novel
      fusion algorithm for infrared and visible images that is based on different
      constraints in non-subsampled shearlet transform (NSST) domain is proposed. There
      are high bands and low bands of images that are decomposed by the NSST. After
      analyzing the characters of the bands, fusing the high level bands by the
      gradient constraint, the fused image can obtain more details; fusing the low
      bands by the constraint of saliency in the images, the targets are more salient.
      Before the inverse NSST, the Nash equilibrium is used to update the coefficient.
      The fused images and the quantitative results demonstrate that our method is more
      effective in reserving details and highlighting the targets when compared with
      other state-of-the-art methods.

PMID- 29641506
TI  - Drone Mission Definition and Implementation for Automated Infrastructure
      Inspection Using Airborne Sensors.
AB  - This paper describes a Mission Definition System and the automated flight process
      it enables to implement measurement plans for discrete infrastructure inspections
      using aerial platforms, and specifically multi-rotor drones. The mission
      definition aims at improving planning efficiency with respect to state-of-the-art
      waypoint-based techniques, using high-level mission definition primitives and
      linking them with realistic flight models to simulate the inspection in advance.
      It also provides flight scripts and measurement plans which can be executed by
      commercial drones. Its user interfaces facilitate mission definition, pre-flight
      3D synthetic mission visualisation and flight evaluation. Results are delivered
      for a set of representative infrastructure inspection flights, showing the
      accuracy of the flight prediction tools in actual operations using automated
      flight control.

PMID- 29641507
TI  - Synthesis, Crystal Structure and DFT Studies of a New Dinuclear Ag(I)-Malonamide
      Complex.
AB  - The synthesis and structural aspects of a new dinuclear silver (I) complex with
      malonamide type ligand (L) is reported. Each Ag ion in the [Ag2L2(NO3)2].H2O
      complex is coordinated to two ligands, L, each acting as a bridged ligand via its
      two pyridine arms; Ag(I) acts as a connector between them. Two types of Ag
      ligands close contacts were detected: Ag-N1, Ag-N4 from the two L units, and Ag
      O5, Ag-O6 from the two nitrate anions, wherein both the nitrate ions are inside
      the cage formed by the [Ag2L2] unit. The coordination geometry around each Ag(I)
      is a distorted tetrahedron. The [Ag2L2(NO3)2] complex units are connected by weak
      intermolecular C-H...O interactions. The different intermolecular interactions
      were quantified using Hirshfeld surface analysis. Using two DFT methods (B3LYP
      and WB97XD), the nature and strength of the Ag-N and Ag-O interactions were
      described using atoms in molecules (AIM) and natural bond orbital (NBO) analyses.
      Topological parameters indicated that the strength of the two Ag-N bonds was
      similar, while that of the two Ag-O interactions were significantly different.
      Moreover, the Ag-N interactions have a predominant covalent character, while the
      Ag-O interactions are mainly ionic. The NBO analysis indicated that the most
      important anti-bonding Ag-orbital in these interactions has an s-orbital
      character.

PMID- 29641508
TI  - Continuous Separation of Light Olefin/Paraffin Mixtures on ZIF-4 by Pressure
      Swing Adsorption and Membrane Permeation.
AB  - In this study, two zeolitic imidazolate frameworks (ZIFs) called ZIF-4 and ZIF
      zni (zni is the network topology) were characterized by sorption studies
      regarding their paraffin/olefin separation potential. In particular, equilibrated
      pure and mixed gas adsorption isotherms of ethane and ethene were recorded at 293
      K up to 3 MPa. ZIF-4 exhibits selectivities for ethane in the range of 1.5-3,
      which is promising for continuous pressure swing adsorption (PSA). ZIF-4 shows
      high cycle stability with promising separation potential regarding ethane, which
      results in purification of the more industrial desired olefin. Furthermore, both
      ZIF materials were implemented in Matrimid to prepare a mixed matrix membrane
      (MMM) and were used in the continuous separation of a propane/propene mixture.
      The separation performance of the neat polymer is drastically increased after
      embedding porous ZIF-4 crystals in the Matrimid matrix, especially at higher feed
      pressures (3-5 barg). Due to the smaller kinetic diameter of the olefin, the
      permeability is higher compared to the paraffin.

PMID- 29641509
TI  - Race, Socioeconomic Status, and Health during Childhood: A Longitudinal
      Examination of Racial/Ethnic Differences in Parental Socioeconomic Timing and
      Child Obesity Risk.
AB  - Prior research suggests that socioeconomic standing during the early years of
      life, particularly in utero, is associated with child health. However, it is
      unclear whether socioeconomic benefits are only maximized at very young ages.
      Moreover, given the link between socioeconomic status (SES) and race, research is
      inconclusive whether any SES benefits during those younger ages would uniformly
      benefit all racial and ethnic groups. Using 1986-2014 data from the National
      Longitudinal Study of Youth (NLSY79), this study examines the impact of
      socioeconomic timing on child weight outcomes by race. Specifically, this
      research investigates whether specific points exist where socioeconomic
      investment would have higher returns on child health. Findings suggest that both
      the timing and the type of socioeconomic exposure is important to understanding
      child weight status. SES, particularly mother's employment and father's
      education, is important in determining child health, and each measure is linked
      to weight gain differently for White, Black, and Hispanic children at specific
      ages. Policies such as granting more educational access for men and work-family
      balance for women are discussed.

PMID- 29641510
TI  - Transcriptome Analysis of Two Rice Varieties Contrasting for Nitrogen Use
      Efficiency under Chronic N Starvation Reveals Differences in Chloroplast and
      Starch Metabolism-Related Genes.
AB  - The nitrogen use efficiency (NUE) of crop plants is limited and enhancing it in
      rice, a major cereal crop, would be beneficial for farmers and the environment
      alike. Here we report the genome-wide transcriptome analysis of two rice
      genotypes, IR 64 (IR64) and Nagina 22 (N22) under optimal (+N) and chronic
      starvation (-N) of nitrogen (N) from 15-day-old root and shoot tissues. The two
      genotypes were found to be contrasting in their response to -N; IR64 root
      architecture and root dry weight remained almost equivalent to that under +N
      conditions, while N22 showed high foraging ability but a substantial reduction in
      biomass under -N. Similarly, the photosynthetic pigments showed a drastic
      reduction in N22 under low N, while IR64 was more resilient. Nitrate reductase
      showed significantly low specific activity under -N in both genotypes. Glutamate
      synthase (GOGAT) and citrate synthase CS activity were highly reduced in N22 but
      not in IR64. Transcriptome analysis of these genotypes revealed nearly double the
      number of genes to be differentially expressed (DEGs) in roots (1016) compared to
      shoots (571). The response of the two genotypes to N starvation was distinctly
      different reflecting their morphological/biochemical response with just two and
      eight common DEGs in the root and shoot tissues. There were a total of 385
      nitrogen-responsive DEGs (106 in shoots and 279 in roots) between the two
      genotypes. Fifty-two of the 89 DEGs identified as specific to N22 root tissues
      were also found to be differentially expressed between the two genotypes under 
      N. Most of these DEGs belonged to starch and chloroplast metabolism, followed by
      membrane and signaling proteins. Physical mapping of DEGs revealed 95 DEGs in
      roots and 76 in shoots to be present in quantitative trait loci (QTL) known for
      NUE.

PMID- 29641512
TI  - Perspective on Cancer Therapeutics Utilizing Analysis of Circulating Tumor Cells.
AB  - Various methods are available for cancer screening, and the methods are performed
      depending on the origin site of cancer. Among these methods, biopsy followed by
      medical imaging is the most common. After cancer progression is determined, an
      optimal treatment-such as surgery, chemotherapy, and/or radiation therapy-is
      selected. A new assay has been developed that detects circulating tumor cells
      (CTCs). Tracking changes in CTCs may reveal important tumoral sensitivity
      information or resistance patterns to specific regimens and prompt changes in
      therapy on a personalized basis. Characterization of CTCs at the DNA, RNA, and
      protein levels is important for gaining insight for clinical applications. A
      small number of CTCs can be analyzed to obtain genome information such as the
      progression of cancer including metastasis, even in a single cluster. Although
      many clinical studies, particularly CTC enumeration and detection of specific
      oncogene expression, have increased the success rate of diagnosis and predicting
      prognosis, there is no consensus regarding the technical approaches and various
      aspects of the methodology, making it difficult to standardize optimal methods
      for CTC analysis. However, ongoing technological advances are currently being
      achieved and large-scale clinical studies are being conducted. Applying CTC
      analysis in the clinic would be very useful for advancing diagnosis, prognosis
      prediction, and therapeutics.

PMID- 29641511
TI  - S-Layer Protein-Based Biosensors.
AB  - The present paper highlights the application of bacterial surface (S-) layer
      proteins as versatile components for the fabrication of biosensors. One
      technologically relevant feature of S-layer proteins is their ability to self
      assemble on many surfaces and interfaces to form a crystalline two-dimensional
      (2D) protein lattice. The S-layer lattice on the surface of a biosensor becomes
      part of the interface architecture linking the bioreceptor to the transducer
      interface, which may cause signal amplification. The S-layer lattice as
      ultrathin, highly porous structure with functional groups in a well-defined
      special distribution and orientation and an overall anti-fouling characteristics
      can significantly raise the limit in terms of variety and the ease of bioreceptor
      immobilization, compactness of bioreceptor molecule arrangement, sensitivity,
      specificity, and detection limit for many types of biosensors. The present paper
      discusses and summarizes examples for the successful implementation of S-layer
      lattices on biosensor surfaces in order to give a comprehensive overview on the
      application potential of these bioinspired S-layer protein-based biosensors.

PMID- 29641513
TI  - Sympathetic and Parasympathetic Coactivation Induces Perturbed Heart Rate
      Dynamics in Patients with Paroxysmal Atrial Fibrillation.
AB  - BACKGROUND Recent evidence indicates that sympathetic/parasympathetic
      coactivation (CoA) is causally linked to changes in heart rate (HR) dynamics.
      Whether this is relevant for patients with atrial fibrillation (AF) is unknown.
      MATERIAL AND METHODS In patients with paroxysmal AF (n=26) and age-matched
      controls, (n=10) we investigated basal autonomic outflow and HR dynamics during
      separate sympathetic (cold hand immersion) and parasympathetic activation (O2
      inhalation), as well as during CoA (cold face test). In an additional cohort
      (n=7), HR response was assessed before and after catheter-based pulmonary vein
      isolation (PVI). Ultra-high-density endocardial mapping was performed in patients
      (n=6) before and after CoA. RESULTS Sympathetic activation increased (control:
      74+/-3 vs. 77+/-3 bpm, p=0.0098; AF: 60+/-2 vs. 64+/-2 bpm, p=0.0076) and
      parasympathetic activation decreased HR (control: 71+/-3 vs. 69+/-3 bpm,
      p=0.0547; AF: 60+/-1 vs. 58+/-2 bpm, p<0.0009), while CoA induced a paradoxical
      HR increase in patients with AF (control: 73+/-3 vs. 71+/-3 bpm, p=0.084; AF:
      59+/-2 vs. 61+/-2 bpm, p=0.0006), which was abolished after PVI. Non-linear
      parameters of HR variability (SD1) were impaired during coactivation in patients
      with AF (control: 61+/-7 vs. 69+/-6 ms, p=0.042, AF: 44+/-32 vs. 32+/-5 ms,
      p=0.3929). CoA was associated with a shift of the earliest activation site (18+/
      4 mm) of the sinoatrial nodal region, as documented by ultra-high-density mapping
      (3442+/-343 points per map). CONCLUSIONS CoA perturbs HR dynamics and shifts the
      site of earliest endocardial activation in patients with paroxysmal AF. This
      effect is abolished by PVI, supporting the value of emerging methods targeting
      the intrinsic cardiac autonomic nervous system to treat AF. CoA might be a
      valuable tool to assess cardiac autonomic function in a clinical setting.

PMID- 29641514
TI  - Age is not just a number: Naive T cells increase their ability to persist in the
      circulation over time.
AB  - The processes regulating peripheral naive T-cell numbers and clonal diversity
      remain poorly understood. Conceptually, homeostatic mechanisms must fall into the
      broad categories of neutral (simple random birth-death models), competition
      (regulation of cell numbers through quorum-sensing, perhaps via limiting shared
      resources), adaptation (involving cell-intrinsic changes in homeostatic fitness,
      defined as net growth rate over time), or selection (involving the loss or
      outgrowth of cell populations deriving from intercellular variation in fitness).
      There may also be stably maintained heterogeneity within the naive T-cell pool.
      To distinguish between these mechanisms, we confront very general models of these
      processes with an array of experimental data, both new and published. While
      reduced competition for homeostatic stimuli may impact cell survival or
      proliferation in neonates or under moderate to severe lymphopenia, we show that
      the only mechanism capable of explaining multiple, independent experimental
      studies of naive CD4+ and CD8+ T-cell homeostasis in mice from young adulthood
      into old age is one of adaptation, in which cells act independently and accrue a
      survival or proliferative advantage continuously with their post-thymic age.
      However, aged naive T cells may also be functionally impaired, and so the
      accumulation of older cells via 'conditioning through experience' may contribute
      to reduced immune responsiveness in the elderly.

PMID- 29641516
TI  - Correction: Late Maastrichtian pterosaurs from North Africa and mass extinction
      of Pterosauria at the Cretaceous-Paleogene boundary.
AB  - [This corrects the article DOI: 10.1371/journal.pbio.2001663.].

PMID- 29641515
TI  - Development of an autodissemination strategy for the deployment of novel control
      agents targeting the common malaria mosquito, Anopheles quadrimaculatus say
      (Diptera: Culicidae).
AB  - BACKGROUND: The reduced efficacy of current Anopheline mosquito control methods
      underscores the need to develop new methods of control that exploit unique target
      sites and/or utilizes novel deployment methods. Autodissemination methodologies
      using insect growth regulators (IGRs) is growing in interest and has been shown
      to be effective at controlling Aedes mosquitoes in semi-field and field
      environments, yet little information exists for Anopheline mosquitoes. Therefore,
      we tested the hypothesis that female-driven autodissemination of an IGR combined
      with a new mechanism of action insecticide (Kir channel inhibitor) could be
      employed to reduce Anopheline populations. METHODOLOGY: We studied the ability of
      three IGRs to be transferred to the larval habitat during oviposition in
      laboratory and semi-field environments. Adult mosquitoes were exposed to the
      chemicals for 4 hours immediately after blood feeding and efficacy was tested
      using classical methodologies, including adult emergence inhibition and High
      Performance Liquid Chromatography (HPLC). A complete autodissemination design was
      tested in a semi-field environment. PRINCIPAL FINDINGS: Larval survivability and
      adult emergence were significantly reduced in habitats that were visited by
      novaluron treated adults, but no statistical differences were observed with
      pyriproxyfen or triflumuron. These data suggested novaluron, but not pyriproxyfen
      or triflumuron, was horizontally transferred from the adult mosquito to the
      larval habitat during oviposition. HPLC studies supported the toxicity data and
      showed that novaluron was present in the majority of larval habitats, suggesting
      that novaluron can be horizontally transferred by Anopheles quadrimaculatus.
      Importantly, the combination of novaluron and the Kir channel inhibitor, VU041,
      was capable of reducing adult and larval populations in semi-field environments.
      CONCLUSIONS: Novaluron can be transferred to the adult at a greater efficacy
      and/or is not degraded as quickly during the gonotropic cycle when compared to
      pyriproxyfen or triflumuron. Pending field confirmation, autodissemination
      approaches with novaluron may be a suitable tool to manage Anopheles populations.

PMID- 29641517
TI  - An experimental approach in revisiting the magnetic orientation of cattle.
AB  - In response to the increasing number of observational studies on an apparent
      south-north orientation in non-homing, non-migrating terrestrial mammals, we
      experimentally tested the alignment hypothesis using strong neodymium magnets on
      the resting orientation of individual cattle in Portugal. Contrary to the
      hypothesis, the 34 cows in the experiment showed no directional preference,
      neither with, nor without a strong neodymium magnet fixed to their collar. The
      concurrently performed 2,428 daytime observations-excluding the hottest part of
      the day-of 659 resting individual cattle did not show a south-north alignment
      when at rest either. The preferred compass orientation of these cows was on
      average 130 degrees from the magnetic north (i.e., south east). Cow compass
      orientation correlated significantly with sun direction, but not with wind
      direction. In as far as we can determine, this is the first experimental test on
      magnetic orientation in larger, non-homing, non-migrating mammals. These
      experimental and observational findings do not support previously published
      suggestions on the magnetic south-north alignment in these mammals.

PMID- 29641518
TI  - Correction: SRC-2-mediated coactivation of anti-tumorigenic target genes
      suppresses MYC-induced liver cancer.
AB  - [This corrects the article DOI: 10.1371/journal.pgen.1006650.].

PMID- 29641519
TI  - Chimpanzees show some evidence of selectively acquiring information by using
      tools, making inferences, and evaluating possible outcomes.
AB  - Metacognition refers to thinking about one's thinking or knowing what one knows.
      Research suggests that this ability is not unique to humans and may be shared
      with nonhuman animals. In particular, great apes have shown behaviors on a
      variety of tasks that are suggestive of metacognitive ability. Here we combine a
      metacognitive task, the information-seeking task, with tool use and variable
      forms of initial information provided to chimpanzees to explore how informational
      states impact behavioral responses in these apes. Three chimpanzees were
      presented with an apparatus that contained five locations where food could be
      hidden. If they pointed to the correct location, they received the reward, but
      otherwise they did not. We first replicated several existing findings using this
      method, and then tested novel hypotheses. The chimpanzees were given different
      types of information across the experiments. Sometimes, they were shown the
      location of the food reward. Other times, they were shown only one empty
      location, which was not useful information. The chimpanzees also could use a tool
      to search any of those locations before making a selection. Chimpanzees typically
      used the tool to search out the location of the reward when they could not
      already know where it was, but they did not use the tool when they already had
      been given that information. One chimpanzee made inferences about the location of
      hidden food, even when that food was never shown in that location. The final
      experiment involved hiding foods of differing preference values, and then
      presenting the chimpanzees with different initial knowledge states (i.e., where
      the best food was located, where the less-preferred food was located, or where no
      food was located). All chimpanzees used the tool when they needed to use it to
      find the best possible item on that trial, but responded by choosing a location
      immediately when they did not need the tool. This finding highlights that their
      behavior was not the result of a simple rule following such as pointing to where
      any food had been seen.

PMID- 29641520
TI  - Role of serum immunoglobulins for predicting sarcoidosis outcome: A cohort study.
AB  - BACKGROUND: Sarcoidosis is a systemic granulomatous disease which carries
      variable outcomes. Serum protein electrophoresis is an easily accessible and
      routinely performed examination at diagnosis, in order to search for
      hypergammaglobulinemia, which is frequently found, and to rule out other
      granulomatous diseases such as common variable immunodeficiency. We aimed to
      assess the impact of baseline immunoglobulin level on the outcome of sarcoidosis.
      METHODS: We conducted a retrospective cohort-study, at Rennes University
      Hospital, in which all newly diagnosed patients for whom a serum protein
      electrophoresis had been performed at baseline were enrolled, from 2006 to 2014.
      The main outcome was the need for corticosteroid treatment within 2 years from
      diagnosis, the secondary outcome was the occurrence of relapse among treated
      patients. RESULTS: Eighty patients were included in the study, and 41.25% of them
      exhibited an elevated globulins rate. In univariate analysis, an elevated ACE
      level >70 U/l, Afro-Caribbean origin, and extra-pulmonary involvement, were
      associated with the need for corticosteroid treatment. In multivariate analysis,
      only ACE elevation (OR = 1.03, IC95% 1.01-1.05, p = 0.009) and extra-pulmonary
      involvement (OR = 5.8, IC95% 1.4-24, p = 0.015) were significant. Immunoglobulin
      level was not associated with the main outcome. Regarding the secondary outcome,
      none of the studied features were predictive of relapse among the 34 treated
      patients followed for two years. CONCLUSIONS: There was no relation between the
      immunoglobulin level at diagnosis and the evolution of sarcoidosis. An elevated
      ACE level and the presence of initial extra-pulmonary involvement were both
      associated with a more severe course of the disease necessitating a
      corticosteroid treatment.

PMID- 29641521
TI  - TGFbeta signaling related genes are involved in hormonal mediation during termite
      soldier differentiation.
AB  - A working knowledge of the proximate factors intrinsic to sterile caste
      differentiation is necessary to understand the evolution of eusocial insects.
      Genomic and transcriptomic analyses in social hymenopteran insects have resulted
      in the hypothesis that sterile castes are generated by the novel function of co
      opted or recruited universal gene networks found in solitary ancestors. However,
      transcriptome analysis during caste differentiation has not been tested in
      termites, and evolutionary processes associated with acquiring the caste are
      still unknown. Termites possess the soldier caste, which is regarded as the first
      acquired permanently sterile caste in the taxon. In this study, we performed a
      comparative transcriptome analysis in termite heads during 3 molting processes,
      i.e., worker, presoldier and soldier molts, under natural conditions in an
      incipient colony of the damp-wood termite Zootermopsis nevadensis. Although
      similar expression patterns were observed during each molting process, more than
      50 genes were shown to be highly expressed before the presoldier (intermediate
      stage of soldier) molt. We then performed RNA interference (RNAi) of the
      candidate 13 genes, including transcription factors and uncharacterized protein
      genes, during presoldier differentiation induced by juvenile hormone (JH) analog
      treatment. Presoldiers induced after RNAi of two genes related to TGFbeta
      (Transforming growth factor beta) signaling were extremely unusual and possessed
      soldier-like phenotypes. These individuals also displayed aggressive behaviors
      similar to natural soldiers when confronted with Formica ants as hypothetical
      enemies. These presoldiers never molted into the next instar, presumably due to
      the decreased expression levels of the molting hormone (20-hydroxyecdysone; 20E)
      signaling genes. These results suggest that TGFbeta signaling was acquired for
      the novel function of regulating between JH and 20E signaling during soldier
      differentiation in termites.

PMID- 29641522
TI  - Prognostic model for psychological outcomes in ambulatory surgery patients: A
      prospective study using a structural equation modeling framework.
AB  - INTRODUCTION: Surgical procedures are increasingly carried out in a day-case
      setting. Along with this increase, psychological outcomes have become prominent.
      The objective was to evaluate prospectively the prognostic effects of
      sociodemographic, medical, and psychological variables assessed before day-case
      surgery on psychological outcomes after surgery. METHODS: The study was carried
      out between October 2010 and September 2011. We analyzed 398 mixed patients, from
      a randomized controlled trial, undergoing day-case surgery at a university
      medical center. Structural equation modeling was used to jointly study
      presurgical prognostic variables relating to sociodemographics (age, sex,
      nationality, marital status, having children, religion, educational level,
      employment), medical status (BMI, heart rate), and psychological status
      associated with anxiety (State-Trait Anxiety Inventory (STAI), Hospital Anxiety
      and Depression Scale (HADS-A)), fatigue (Multidimensional Fatigue Inventory
      (MFI)), aggression (State-Trait Anger Scale (STAS)), depressive moods (HADS-D),
      self-esteem, and self-efficacy. We studied psychological outcomes on day 7 after
      surgery, including anxiety, fatigue, depressive moods, and aggression regulation.
      RESULTS: The final prognostic model comprised the following variables: anxiety
      (STAI, HADS-A), fatigue (MFI), depression (HADS-D), aggression (STAS), self
      efficacy, sex, and having children. The corresponding psychological variables as
      assessed at baseline were prominent (i.e. standardized regression coefficients >=
      0.20), with STAI-Trait score being the strongest predictor overall. STAI-State
      (adjusted R2 = 0.44), STAI-Trait (0.66), HADS-A (0.45) and STAS-Trait (0.54) were
      best predicted. CONCLUSION: We provide a prognostic model that adequately
      predicts multiple postoperative outcomes in day-case surgery. Consequently, this
      enables timely identification of vulnerable patients who may require additional
      medical or psychological preventive treatment or-in a worst-case scenario-could
      be unselected for day-case surgery.

PMID- 29641523
TI  - Melatonin enhances antioxidant molecules in the placenta, reduces secretion of
      soluble fms-like tyrosine kinase 1 (sFLT) from primary trophoblast but does not
      rescue endothelial dysfunction: An evaluation of its potential to treat
      preeclampsia.
AB  - Preeclampsia is one of the most serious complications of pregnancy. Currently
      there are no medical treatments. Given placental oxidative stress may be an early
      trigger in the pathogenesis of preeclampsia, therapies that enhance antioxidant
      pathways have been proposed as treatments. Melatonin is a direct free-radical
      scavenger and indirect antioxidant. We performed in vitro assays to assess
      whether melatonin 1) enhances the antioxidant response element genes (heme
      oxygenase 1, (HO-1), glutamate-cysteine ligase (GCLC), NAD(P)H:quinone acceptor
      oxidoreductase 1 (NQO1), thioredoxin (TXN)) or 2) alters secretion of the anti
      angiogenic factors soluble fms-like tyrosine kinase-1 (sFLT) or soluble endoglin
      (sENG) from human primary trophoblasts, placental explants and human umbilical
      vein endothelial cells (HUVECs) and 3) can rescue TNF-alpha induced endothelial
      dysfunction. In primary trophoblast melatonin treatment increased expression of
      the antioxidant enzyme TXN. Expression of TXN, GCLC and NQO1 was upregulated in
      placental tissue with melatonin treatment. HUVECs treated with melatonin showed
      an increase in both TXN and GCLC. Melatonin did not increase HO-1 expression in
      any of the tissues examined. Melatonin reduced sFLT secretion from primary
      trophoblasts, but had no effect on sFLT or sENG secretion from placental explants
      or HUVECs. Melatonin did not rescue TNF-alpha induced VCAM-1 and ET-1 expression
      in endothelial cells. Our findings suggest that melatonin induces antioxidant
      pathways in placenta and endothelial cells. Furthermore, it may have effects in
      reducing sFLT secretion from trophoblast, but does not reduce endothelial
      dysfunction. Given it is likely to be safe in pregnancy, it may have potential as
      a therapeutic agent to treat or prevent preeclampsia.

PMID- 29641524
TI  - A reassessment of the early archaeological record at Leang Burung 2, a Late
      Pleistocene rock-shelter site on the Indonesian island of Sulawesi.
AB  - This paper presents a reassessment of the archaeological record at Leang Burung
      2, a key early human occupation site in the Late Pleistocene of Southeast Asia.
      Excavated originally by Ian Glover in 1975, this limestone rock-shelter in the
      Maros karsts of Sulawesi, Indonesia, has long held significance in our
      understanding of early human dispersals into 'Wallacea', the vast zone of oceanic
      islands between continental Asia and Australia. We present new stratigraphic
      information and dating evidence from Leang Burung 2 collected during the course
      of our excavations at this site in 2007 and 2011-13. Our findings suggest that
      the classic Late Pleistocene modern human occupation sequence identified
      previously at Leang Burung 2, and proposed to span around 31,000 to 19,000
      conventional 14C years BP (~35-24 ka cal BP), may actually represent an amalgam
      of reworked archaeological materials. Sources for cultural materials of mixed
      ages comprise breccias from the rear wall of the rock-shelter-remnants of older,
      eroded deposits dated to 35-23 ka cal BP-and cultural remains of early Holocene
      antiquity. Below the upper levels affected by the mass loss of Late Pleistocene
      deposits, our deep-trench excavations uncovered evidence for an earlier hominin
      presence at the site. These findings include fossils of now-extinct proboscideans
      and other 'megafauna' in stratified context, as well as a cobble-based stone
      artifact technology comparable to that produced by late Middle Pleistocene
      hominins elsewhere on Sulawesi.

PMID- 29641525
TI  - Personal microbiome analysis improves student engagement and interest in
      Immunology, Molecular Biology, and Genomics undergraduate courses.
AB  - A critical area of emphasis for science educators is the identification of
      effective means of teaching and engaging undergraduate students. Personal
      microbiome analysis is a means of identifying the microbial communities found on
      or in our body. We hypothesized the use of personal microbiome analysis in the
      classroom could improve science education by making courses more applied and
      engaging for undergraduate students. We determined to test this prediction in
      three Brigham Young University undergraduate courses: Immunology, Advanced
      Molecular Biology Laboratory, and Genomics. These three courses have a two-week
      microbiome unit and students during the 2016 semester students could submit their
      own personal microbiome kit or use the demo data, whereas during the 2017
      semester students were given access to microbiome data from an anonymous
      individual. The students were surveyed before, during, and after the human
      microbiome unit to determine whether analyzing their own personal microbiome
      data, compared to analyzing demo microbiome data, impacted student engagement and
      interest. We found that personal microbiome analysis significantly enhanced the
      engagement and interest of students while completing microbiome assignments, the
      self-reported time students spent researching the microbiome during the two week
      microbiome unit, and the attitudes of students regarding the course overall.
      Thus, we found that integrating personal microbiome analysis in the classroom was
      a powerful means of improving student engagement and interest in undergraduate
      science courses.

PMID- 29641527
TI  - Impact of HIV knowledge and stigma on the uptake of HIV testing - Results from a
      community-based participatory research survey among migrants from sub-Saharan
      Africa in Germany.
AB  - BACKGROUND: In 2015, 3,674 new HIV diagnoses were notified in Germany; 16% of
      those newly diagnosed cases originated from sub-Saharan Africa (sSA). One quarter
      of the newly diagnosed cases among migrants from sSA (MisSA) are notified as
      having acquired the HIV infection in Germany. In order to reach MisSA with HIV
      testing opportunities, we aimed to identify which determinants influence the
      uptake of HIV testing among MisSA in Germany. METHODS: To identify those
      determinants, we conducted a quantitative cross-sectional survey among MisSA in
      Germany. The survey was designed in a participatory process that included MisSA
      and other stakeholders in HIV-prevention. Peer researchers recruited participants
      to complete standardized questionnaires on HIV knowledge and testing. We
      conducted multivariable analyses (MVA) to identify determinants associated with
      ever having attended voluntary HIV testing; and another MVA to identify
      determinant associated with having had the last voluntary HIV test in Germany.
      RESULTS: Peer researchers recruited 2,782 participants eligible for inclusion in
      the MVA. Of these participants, 59.9% (1,667/2,782) previously had an HIV test.
      For each general statement about HIV that participants knew prior to
      participation in the study, the odds of having been tested increased by 19% (OR
      1.19; 95%-CI: 1.11-1.27). Participants reporting that HIV is a topic that is
      discussed in their community had 92% higher odds of having been tested for HIV
      (OR 1.92; 95%-CI: 1.60-2.31). Migrants living in Germany for less than a year had
      the lowest odds of having had their last HIV test in Germany (OR 0.17; 95%-CI:
      0.11-0.27). Additionally, MisSA 18 to 25 years (OR 0.55; 95%-CI: 0.42-0.73) and
      participants with varied sexual partners and inconsistent condom use (OR 0.75;
      95%-CI: 0.44-0.97) had significantly lower odds of having had their last HIV test
      in Germany. DISCUSSION: Through participatory research, we were able to show that
      knowledge about HIV and discussing HIV in communities increased the odds of
      having attended HIV testing among MisSA. However, recent migrants and young
      sexually active people are among the least reached by testing offers in Germany.
      Community-based interventions may present opportunities to reach such migrants
      and improve knowledge and increase discussion about HIV.

PMID- 29641526
TI  - Persistent organic pollutants in Antarctic notothenioid fish and invertebrates
      associated with trophic levels.
AB  - Notothenioid fish and invertebrate samples from Antarctica were collected in the
      austral summer of 2009, and analyzed for persistent organic pollutants (POPs),
      including polycyclic aromatic hydrocarbons (PAHs), organochlorine pesticides
      (OCPs), and polybrominated diphenylethers (PBDEs), as well as delta13C and
      delta15N stable isotopes for trophic level determination. In this study, the POP
      levels in the Antarctic biota samples were found to be ranked in the following
      order: OCPs > PAHs >> PBDEs. The POP levels in notothenioid fish and krill
      correlate to trophic levels; however, the POP concentrations in intertidal
      benthic invertebrates are higher than in notothenioid fish implying that specific
      biogeochemical factors may affect bioaccumulation in the Antarctica ecosystem.
      Biomagnification of POPs may have a smaller role than bioconcentration in
      Antarctica environment. In addition to the source, transport, exposure, and
      absorption for each group of POPs in the short food chain in Antarctica, the
      biological variation among species, interaction habitats, diet and metabolism are
      also factors for future studies on contaminant bioaccumulation.

PMID- 29641528
TI  - Gender-based discrimination and unprotected receptive anal intercourse among
      transgender women in Brazil: A mixed methods study.
AB  - INTRODUCTION: Discrimination related to gender identity may directly influence
      vulnerability to HIV through increased exposure to unprotected receptive anal
      intercourse (URAI). Little is known about the relationship between gender-based
      discrimination (GBD) and URAI with stable partners among transgender women.
      METHODS: This mixed-methods research began with a cross-sectional survey
      conducted between 2014 and 2016 with transgender women in Salvador, the capital
      city in one of the poorest regions in Brazil. Respondent-driven sampling was used
      to recruit the study population. GBD was defined through Latent Class Analysis.
      Additionally, 19 semi-structured interviews with participants were transcribed
      and analyzed through thematic content analysis. RESULTS: URAI with stable
      partners was commonly reported (37.3%). GDB was positively associated with URAI
      among stable partners (OR = 6.47; IC 95%: 1.67-25.02). The analysis of the
      interviews illustrated how GBD impacted transgender women in diverse ways.
      Experiences with GBD perpetrated by the family often initiated a trajectory of
      economic vulnerability that led many to engage in survival sex work. The constant
      experience with GBD contributed to participants feeling an immense sense of trust
      with their stable partners, ultimately diminished their desire to use condoms.
      Further, the high frequency of GBD contributed to poor mental health overall,
      though some participants said engagement in transgender advocacy efforts provided
      a vital source of resilience and support. CONCLUSION: Our mixed-method study
      capitalizes upon the strengths of diverse data sets to produce a holistic
      understanding of GBD and URAI with stable partners. Furthermore, by confirming
      the association between greater GBD and URAI, we have demonstrated how GBD can
      impact condom negotiation in diverse relationships.

PMID- 29641529
TI  - Variation in social systems within Chaetodon butterflyfishes, with special
      reference to pair bonding.
AB  - For many animals, affiliative relationships such as pair bonds form the
      foundation of society and are highly adaptive. Animal systems amenable for
      comparatively studying pair bonding are important for identifying underlying
      biological mechanisms, but mostly exist in mammals. Better establishing fish
      systems will enable comparison of pair bonding mechanisms across taxonomically
      distant lineages that may reveal general underlying mechanistic principles. We
      examined the utility of wild butterflyfishes (f: Chaetodontidae; g: Chaetodon)
      for comparatively studying pair bonding. Using stochastic character mapping, we
      provide the first analysis of the evolutionary history of butterflyfish
      sociality, revealing that pairing is ancestral, with at least seven independent
      transitions to gregarious grouping and solitary behavior since the late Miocene.
      We then formally verified social systems in six sympatric and wide-spread species
      representing a clade with one ancestrally reconstructed transition from paired to
      solitary grouping at Lizard Island, Australia. In situ observations of the size,
      selective affiliation and aggression, fidelity, and sex composition of social
      groups confirmed that Chaetodon baronessa, C. lunulatus, and C. vagabundus are
      predominantly pair bonding, whereas C. rainfordi, C. plebeius, and C.
      trifascialis are predominantly solitary. Even in the predominantly pair bonding
      species, C. lunulatus, a proportion of adults (15%) are solitary. Importantly,
      inter- and intra-specific differences in social systems do not co-vary with other
      previously established attributes, including parental care. Hence, the proposed
      butterflyfish populations are promising for inter- and intra-species comparative
      analyses of pair bonding and its mechanistic underpinnings. Avenues for further
      developing the system are proposed, including determining whether the
      aforementioned utility of these species applies across their geographic
      disruptions.

PMID- 29641530
TI  - Are 6-month-old human infants able to transfer emotional information (happy or
      angry) from voices to faces? An eye-tracking study.
AB  - The present study examined whether 6-month-old infants could transfer amodal
      information (i.e. independently of sensory modalities) from emotional voices to
      emotional faces. Thus, sequences of successive emotional stimuli (voice or face
      from one sensory modality -auditory- to another sensory modality -visual-),
      corresponding to a cross-modal transfer, were displayed to 24 infants. Each
      sequence presented an emotional (angry or happy) or neutral voice, uniquely,
      followed by the simultaneous presentation of two static emotional faces (angry or
      happy, congruous or incongruous with the emotional voice). Eye movements in
      response to the visual stimuli were recorded with an eye-tracker. First, results
      suggested no difference in infants' looking time to happy or angry face after
      listening to the neutral voice or the angry voice. Nevertheless, after listening
      to the happy voice, infants looked longer at the incongruent angry face (the
      mouth area in particular) than the congruent happy face. These results revealed
      that a cross-modal transfer (from auditory to visual modalities) is possible for
      6-month-old infants only after the presentation of a happy voice, suggesting that
      they recognize this emotion amodally.

PMID- 29641531
TI  - Comparison of the oral microbiome in mouthwash and whole saliva samples.
AB  - Population-based epidemiologic studies can provide important insight regarding
      the role of the microbiome in human health and disease. Buccal cells samples
      using commercial mouthwash have been obtained in large prospective cohorts for
      the purpose of studying human genomic DNA. We aimed to better understand if these
      mouthwash samples are also a valid resource for the study of the oral microbiome.
      We collected one saliva sample and one Scope mouthwash sample from 10 healthy
      subjects. Bacterial 16S rRNA genes from both types of samples were amplified,
      sequenced, and assigned to bacterial taxa. We comprehensively compared these
      paired samples for bacterial community composition and individual taxonomic
      abundance. We found that mouthwash samples yielded similar amount of bacterial
      DNA as saliva samples (p from Student's t-test for paired samples = 0.92).
      Additionally, the paired samples had similar within sample diversity (p from =
      0.33 for richness, and p = 0.51 for Shannon index), and clustered as pairs for
      diversity when analyzed by unsupervised hierarchical cluster analysis. No
      significant difference was found in the paired samples with respect to the
      taxonomic abundance of major bacterial phyla, Bacteroidetes, Firmicutes,
      Proteobacteria, Fusobacteria, and Actinobacteria (FDR adjusted q values from
      Wilcoxin signed-rank test = 0.15, 0.15, 0.87, 1.00 and 0.15, respectively), and
      all identified genera, including genus Streptococcus (q = 0.21), Prevotella (q =
      0.25), Neisseria (q = 0.37), Veillonella (q = 0.73), Fusobacterium (q = 0.19),
      and Porphyromonas (q = 0.60). These results show that mouthwash samples perform
      similarly to saliva samples for analysis of the oral microbiome. Mouthwash
      samples collected originally for analysis of human DNA are also a resource
      suitable for human microbiome research.

PMID- 29641532
TI  - Germline mutations in candidate predisposition genes in individuals with
      cutaneous melanoma and at least two independent additional primary cancers.
AB  - BACKGROUND: While a number of autosomal dominant and autosomal recessive cancer
      syndromes have an associated spectrum of cancers, the prevalence and variety of
      cancer predisposition mutations in patients with multiple primary cancers have
      not been extensively investigated. An understanding of the variants predisposing
      to more than one cancer type could improve patient care, including screening and
      genetic counselling, as well as advancing the understanding of tumour
      development. METHODS: A cohort of 57 patients ascertained due to their cutaneous
      melanoma (CM) diagnosis and with a history of two or more additional non
      cutaneous independent primary cancer types were recruited for this study. Patient
      blood samples were assessed by whole exome or whole genome sequencing. We
      focussed on variants in 525 pre-selected genes, including 65 autosomal dominant
      and 31 autosomal recessive cancer predisposition genes, 116 genes involved in the
      DNA repair pathway, and 313 commonly somatically mutated in cancer. The same
      genes were analysed in exome sequence data from 1358 control individuals
      collected as part of non-cancer studies (UK10K). The identified variants were
      classified for pathogenicity using online databases, literature and in silico
      prediction tools. RESULTS: No known pathogenic autosomal dominant or previously
      described compound heterozygous mutations in autosomal recessive genes were
      observed in the multiple cancer cohort. Variants typically found somatically in
      haematological malignancies (in JAK1, JAK2, SF3B1, SRSF2, TET2 and TYK2) were
      present in lymphocyte DNA of patients with multiple primary cancers, all of whom
      had a history of haematological malignancy and cutaneous melanoma, as well as
      colorectal cancer and/or prostate cancer. Other potentially pathogenic variants
      were discovered in BUB1B, POLE2, ROS1 and DNMT3A. Compared to controls, multiple
      cancer cases had significantly more likely damaging mutations (nonsense,
      frameshift ins/del) in tumour suppressor and tyrosine kinase genes and higher
      overall burden of mutations in all cancer genes. CONCLUSIONS: We identified
      several pathogenic variants that likely predispose to at least one of the tumours
      in patients with multiple cancers. We additionally present evidence that there
      may be a higher burden of variants of unknown significance in 'cancer genes' in
      patients with multiple cancer types. Further screens of this nature need to be
      carried out to build evidence to show if the cancers observed in these patients
      form part of a cancer spectrum associated with single germline variants in these
      genes, whether multiple layers of susceptibility exist (oligogenic or polygenic),
      or if the occurrence of multiple different cancers is due to random chance.

PMID- 29641533
TI  - Handgrip strength is associated with improved spirometry in adolescents.
AB  - INTRODUCTION: Pulmonary rehabilitation, including aerobic exercise and strength
      training, improves function, such as spirometric indices, in lung disease.
      However, we found spirometry did not correlate with physical activity (PA) in
      healthy adolescents (Smith ERJ: 42(4), 2016). To address whether muscle strength
      did, we measured these adolescents' handgrip strength and correlated it with
      spirometry. METHODS: In 1846 non-smoking, non-asthmatic Germans (age 15.2 years,
      47% male), we modeled spirometric indices as functions of handgrip strength by
      linear regression in each sex, corrected for factors including age, height, and
      lean body mass. RESULTS: Handgrip averaged 35.4 (SD 7.3) kg in boys, 26.6 (4.2)
      in girls. Spirometric volumes and flows increased linearly with handgrip. In boys
      each kg handgrip was associated with about 28 mL greater FEV1 and FVC; 60 mL/sec
      faster PEF; and 38 mL/sec faster FEF2575. Effects were 10-30% smaller in girls
      (all p<0.0001) and stable when Z-scores for spirometry and grip were modeled,
      after further correction for environment and/or other exposures, and consistent
      across stages of puberty. CONCLUSIONS: Grip strength was associated with
      spirometry in a cohort of healthy adolescents whose PA was not. Thus, research
      into PA's relationship with lung function should consider strength as well as
      total PA. Strength training may benefit healthy lungs; interventions are needed
      to prove causality.

PMID- 29641534
TI  - Isolation and characterization of an ammonium-oxidizing iron reducer:
      Acidimicrobiaceae sp. A6.
AB  - Acidimicrobiaceae sp. A6 (ATCC, PTA-122488), a strain that has been previously
      reported to play a key role in the oxidation of ammonium (NH4+) under iron
      reducing conditions, has now been isolated from riparian wetland soils in New
      Jersey, USA. Incubations of this strain in a medium containing ferrihydrite as
      the ferric iron [Fe(III)] source, CO2 as the carbon source, under room
      temperature, and a pH of 4.5, resulted in 52% of NH4+ removal over a 20-day
      incubation period, while reducing Fe(III) in the expected stoichiometric ratio
      when NH4+ was oxidized to nitrite with Fe(III) as the electron acceptor. This
      study demonstrates that this new isolated strain is capable of oxidizing NH4+
      while reducing iron under anaerobic conditions.

PMID- 29641535
TI  - Acquired resistance to AZD9291 as an upfront treatment is dependent on ERK
      signaling in a preclinical model.
AB  - AZD9291 (osimertinib) is approved for standard care in patients with EGFR T790M
      positive non-small cell lung cancer (NSCLC) after prior EGFR TKI progression.
      Furthermore, AZD9291 is now being evaluated as a first-line treatment for NSCLC
      patients with activation EGFR mutations. Based on previous experiments,
      resistance to AZD9291 as a first-line treatment may also emerge. Thus,
      identification and understanding of resistance mechanisms to AZD9291 as a first
      line treatment can help direct development of future therapies. AZD9291-resistant
      cells (PC9/AZDR) were established using EGFR inhibitor-naive PC9 cells.
      Resistance mechanisms were analyzed using next-generation sequencing (NGS) and a
      proteome profiler array. Resistance to AZD9291 developed through aberrant
      activation of ERK signaling by an EGFR-independent mechanism. The combination of
      a MEK inhibitor with AZD9291 restored the sensitivity of PC9/AZDR cells in vitro
      and in vivo. PC9/AZDR cells also showed increased MET expression and an HRAS G13R
      mutation. In addition, maspin expression was higher after AZD9291 treatment in
      PC9/AZDR cells. Sustained ERK activation confers resistance to AZD9291 as a first
      line therapy. Thus, co-targeting EGFR and MEK may be an effective strategy to
      overcome resistance to AZD9291.

PMID- 29641536
TI  - Levels of anti-CMV antibodies are modulated by the frequency and intensity of
      virus reactivations in kidney transplant patients.
AB  - Anti-CMV (cytomegalovirus) antibody titers are related to immune alterations and
      increased risk of mortality. To test whether they represent a marker of infection
      history, we analyzed the effect of viral reactivations on the production of
      specific antibodies in kidney transplant patients. We quantified CMV-DNAemia and
      antibody titers in 58 kidney transplant patients before transplantation and
      during a follow-up of 315 days (standard deviation, SD: 134.5 days). In order to
      calculate the intensity of the infection, we plotted the follow-up time of the
      infection on the x-axis and the number of DNA-CMV copies on the y-axis and
      calculated the area under the curve (CMV-AUC). The degree of T-lymphocyte
      differentiation was analyzed with flow cytometry, the cells were labelled with
      different monoclonal antibodies in order to distinguish their differentiation
      state, from naive T-cells to senescent T-cells. Peak viremia was significantly
      higher in patients experiencing a primary infection (VI) compared to patients
      experiencing viral reactivation (VR). Our data indicate that the overall CMV
      viral load over the course of a primary infection is significantly higher than in
      a reactivation of a previously established infection. Whereas patients who
      experienced an episode of CMV reactivation during the course of our observation
      showed increased levels of CMV-specific antibodies, patients who did not
      experience CMV reactivation (WVR) showed a drop in CMV antibody levels that
      corresponds to an overall drop in antibody levels, probably due to the continuing
      immunosuppression after the renal transplant. We found a positive correlation
      between the CMV viremia over the course of the infection or reactivation and the
      CMV-specific antibody titers in the examined patients. We also observed a
      positive correlation between anti-CMV titers and T-cell differentiation. In
      conclusion, our data show that anti-CMV antibody titers are related to the course
      of CMV infection in kidney transplant patients.

PMID- 29641537
TI  - Broad cross-reactive IgG responses elicited by adjuvanted vaccination with
      recombinant influenza hemagglutinin (rHA) in ferrets and mice.
AB  - Annual immunization against influenza virus is a large international public
      health effort. Accumulating evidence suggests that antibody mediated cross
      reactive immunity against influenza hemagglutinin (HA) strongly correlates with
      long-lasting cross-protection against influenza virus strains that differ from
      the primary infection or vaccination strain. However, the optimal strategies for
      achieving highly cross-reactive antibodies to the influenza virus HA have not yet
      to be defined. In the current study, using Luminex-based mPlex-Flu assay,
      developed by our laboratory, to quantitatively measure influenza specific IgG
      antibody mediated cross-reactivity, we found that prime-boost-boost vaccination
      of ferrets with rHA proteins admixed with adjuvant elicited higher magnitude and
      broader cross-reactive antibody responses than that induced by actual influenza
      viral infection, and this cross-reactive response likely correlated with
      increased anti-stalk reactive antibodies. We observed a similar phenomenon in
      mice receiving three sequential vaccinations with rHA proteins from either
      A/California/07/2009 (H1N1) or A/Hong Kong/1/1968 (H3N2) viruses admixed with
      Addavax, an MF59-like adjuvant. Using this same mouse vaccination model, we
      determined that Addavax plays a more significant role in the initial priming
      event than in subsequent boosts. We also characterized the generation of cross
      reactive antibody secreting cells (ASCs) and memory B cells (MBCs) when comparing
      vaccination to viral infection. We have also found that adjuvant plays a critical
      role in the generation of long-lived ASCs and MBCs cross-reactive to influenza
      viruses as a result of vaccination with rHA of influenza virus, and the observed
      increase in stalk-reactive antibodies likely contributes to this IgG mediated
      broad cross-reactivity.

PMID- 29641538
TI  - Prognostic impact of systolic blood pressure variability in people with diabetes.
AB  - OBJECTIVE: Blood pressure variability (BPV) has been associated with risk of
      cardiovascular events in observational studies, independently of mean BP levels.
      In states with higher autonomic imbalance, such as in diabetes, the importance of
      BP variability may theoretically be even greater. We aimed to investigate the
      incremental value of BPV for prediction of cardiovascular and all-cause mortality
      in patients with type 2 diabetes. METHODS: We identified 9,855 patients without
      pre-existing cardiovascular disease who did not change BP-lowering treatment
      during the observation period from a Swedish primary health care cohort of
      patients with type 2 diabetes. BPV was summarized as the standard deviation (SD),
      coefficient of variation (CV), or variation independent of mean (VIM). Patients
      were followed for a median of 4 years and associations with cardiovascular and
      all-cause mortality were investigated using Cox proportional hazards models.
      RESULTS: BPV was not associated with cardiovascular specific or all-cause
      mortality in the total sample. In patients who were not on BP-lowering drugs
      during the observation period (n = 2,949), variability measures were associated
      with all-cause mortality: hazard ratios were 1.05, 1.04 and 1.05 for 50%
      increases in SD, CV and VIM, respectively, adjusted for Framingham risk score
      risk factors, including mean BP. However, the addition of the variability
      measures in this subgroup only led to very minimal improvement in discrimination,
      indicating they may have limited clinical usefulness (change in C-statistic
      ranged from 0.000-0.003 in all models). CONCLUSIONS: Although BPV was
      independently associated with all-cause mortality in diabetes patients in primary
      care who did not have pre-existing cardiovascular disease or BP-lowering drugs,
      it may be of minimal clinical usefulness above and beyond that of other routinely
      measured predictors, including mean BP.

PMID- 29641539
TI  - Production of omega-3 enriched tilapia through the dietary use of algae meal or
      fish oil: Improved nutrient value of fillet and offal.
AB  - The goal of this project was to increase the nutrient value of fillets, by
      product muscle, and offal of aquacultured tilapia. A diet that includes seafood
      with a high omega-3 (n-3) fatty acid content, more specifically eicosapentaenoic
      acid (EPA) and docosahexaenoic acid (DHA), are known to have numerous health
      benefits for consumers. Improved nutrient value of the offal may also attract new
      market opportunities for the aquaculture industry. Tilapia were cultured on
      different experimental feeds that contained various levels of n-3 fatty acids
      from either fish oil (FO) or algae meal (AM) that were used to replace corn oil.
      The experimental diets included a control (corn oil 6.3%), FO1%, FO3%, FO5%,
      AM1.75%, AM5.26%, and AM8.77%. All diets were formulated to be isocaloric,
      isonitrogenous, and isolipid. Three hundred and fifty tilapia with an initial
      mean weight of 158+/-2 g were cultured in a recirculating aquaculture system
      (seven diets replicated at the tank level, 14 tanks, 25 fish per tank). For all
      of the production performance data, no differences (P>0.05) were observed between
      the experimental groups which included survival (overall mean +/- standard error,
      99.4+/-0.3%), growth per week (45.4+/-1.0 g/wk), food conversion ratio (1.32+/
      0.03), fillet yield (44.4+/-0.2%), hepatosomatic index (1.61+/-0.02),
      viscerosomatic index (2.86+/-0.06), and mesenteric fat index (0.97+/-0.04).
      Fillet and rib meat tissues were collected at weeks four and eight, and liver and
      mesenteric fat tissues were collected at week eight. Fatty acids were extracted,
      methylated and identified with gas chromatography-mass spectrometry. All tissues
      had improved fatty acid profiles (higher n-3, lower n-6, n-6:n-3) with increasing
      levels of FO and AM in the diet. For example, the best diet for significantly
      (P<0.05) improving the lipid profile in tilapia fillets at week eight was diet
      AM8.77%. In the fillet, total n-3 was increased (control versus AM8.77%) from
      151.2+/-19.0 to 438.7+/-14.2 mg per 4 ounce (113 g) serving and n-6:n-3 ratio was
      improved from 5.19+/-0.76 to 1.29+/-0.03.

PMID- 29641540
TI  - Muscle mass, BMI, and mortality among adults in the United States: A population
      based cohort study.
AB  - BACKGROUND: The level of body-mass index (BMI) associated with the lowest risk of
      death remains unclear. Although differences in muscle mass limit the utility of
      BMI as a measure of adiposity, no study has directly examined the effect of
      muscle mass on the BMI-mortality relationship. METHODS: Body composition was
      measured by dual-energy x-ray absorptiometry in 11,687 participants of the
      National Health and Nutrition Examination Survey 1999-2004. Low muscle mass was
      defined using sex-specific thresholds of the appendicular skeletal muscle mass
      index (ASMI). Proportional hazards models were created to model associations with
      all-cause mortality. RESULTS: At any level of BMI >=22, participants with low
      muscle mass had higher body fat percentage (%TBF), an increased likelihood of
      diabetes, and higher adjusted mortality than other participants. Increases in
      %TBF manifested as 30-40% smaller changes in BMI than were observed in
      participants with preserved muscle mass. Excluding participants with low muscle
      mass or adjustment for ASMI attenuated the risk associated with low BMI,
      magnified the risk associated with high BMI, and shifted downward the level of
      BMI associated with the lowest risk of death. Higher ASMI was independently
      associated with lower mortality. Effects were similar in never-smokers and ever
      smokers. Additional adjustment for waist circumference eliminated the risk
      associated with higher BMI. Results were unchanged after excluding unintentional
      weight loss, chronic illness, early mortality, and participants performing muscle
      strengthening exercises or recommended levels of physical activity. CONCLUSIONS:
      Muscle mass mediates associations of BMI with adiposity and mortality and is
      inversely associated with the risk of death. After accounting for muscle mass,
      the BMI associated with the greatest survival shifts downward toward the normal
      range. These results provide a concrete explanation for the obesity paradox.

PMID- 29641541
TI  - Physiological evidence of sensory integration in the electrosensory lateral line
      lobe of Gnathonemus petersii.
AB  - Mormyrid fish rely on reafferent input for active electrolocation. Their
      electrosensory input consists of phase and amplitude information. These are
      encoded by differently tuned receptor cells within the Mormyromasts, A- and B
      cells, respectively, which are distributed over the animal's body. These convey
      their information to two topographically ordered medullary zones in the
      electrosensory lateral line lobe (ELL). The so-called medial zone receives only
      amplitude information, while the dorsolateral zone receives amplitude and phase
      information. Using both sources of information, Mormyrid fish can disambiguate
      electrical impedances. Where and how this disambiguation takes place is presently
      unclear. We here investigate phase-sensitivity downstream from the
      electroreceptors. We provide first evidence of phase-sensitivity in the medial
      zone of ELL. In this zone I-cells consistently decreased their rate to positive
      phase-shifts (6 of 20 cells) and increased their rate to negative shifts (11/20),
      while E-cells of the medial zone (3/9) responded oppositely to I-cells. In the
      dorsolateral zone the responses of E- and I-cells were opposite to those found in
      the medial zone. Tracer injections revealed interzonal projections that
      interconnect the dorsolateral and medial zones in a somatotopic manner. In
      summary, we show that phase information is processed differently in the
      dorsolateral and the medial zones. This is the first evidence for a mechanism
      that enhances the contrast between two parallel sensory channels in Mormyrid
      fish. This could be beneficial for impedance discrimination that ultimately must
      rely on a subtractive merging of these two sensory streams.

PMID- 29641542
TI  - Stomach fullness shapes prey choice decisions in crab plovers (Dromas ardeola).
AB  - Foragers whose energy intake rate is constrained by search and handling time
      should, according to the contingency model (CM), select prey items whose
      profitability exceeds or equals the forager's long-term average energy intake
      rate. This rule does not apply when prey items are found and ingested at a higher
      rate than the digestive system can process them. According to the digestive rate
      model (DRM), foragers in such situations should prefer prey with the highest
      digestive quality, instead of the highest profitability. As the digestive system
      fills up, the limiting constraint switches from ingestion rate to digestion rate,
      and prey choice is expected to change accordingly for foragers making decisions
      over a relative short time window. We use these models to understand prey choice
      in crab plovers (Dromas ardeola), preying on either small burrowing crabs that
      are swallowed whole (high profitability, but potentially inducing a digestive
      constraint) or on larger swimming crabs that are opened to consume only the flesh
      (low profitability, but easier to digest). To parameterize the CM and DRM, we
      measured energy content, ballast mass and handling times for different sized
      prey, and the birds' digestive capacity in three captive individuals.
      Subsequently, these birds were used in ad libitum experiments to test if they
      obeyed the rules of the CM or DRM. We found that crab plovers with an empty
      stomach mainly chose the most profitable prey, matching the CM. When stomach
      fullness increased, the birds switched their preference from the most profitable
      prey to the highest-quality prey, matching the predictions of the DRM. This shows
      that prey choice is context dependent, affected by the stomach fullness of an
      animal. Our results suggest that prey choice experiments should be carefully
      interpreted, especially under captive conditions as foragers often 'fill up' in
      the course of feeding trials.

PMID- 29641543
TI  - Urogenital Chlamydia trachomatis multilocus sequence types and genovar
      distribution in chlamydia infected patients in a multi-ethnic region of Saratov,
      Russia.
AB  - BACKGROUND: This is the first report to characterize the prevalence and genovar
      distribution of genital chlamydial infections among random heterosexual patients
      in the multi-ethnic Saratov Region, located in Southeast Russia. METHODS: Sixty
      one clinical samples (cervical or urethral swabs) collected from a random cohort
      of 856 patients (7.1%) were C. trachomatis (CT) positive in commercial nucleic
      acid amplification tests (NAATs) and duplex TaqMan PCRs. RESULTS: Sequence
      analysis of the VDII region of the ompA gene revealed seven genovars of C.
      trachomatis in PCR-positive patients. The overall genovars were distributed as E
      (41.9%), G (21.6%), F (13.5%), K (9.5%), D (6.8%), J (4.1%), and H (2.7%). CT
      positive samples were from males (n = 12, 19.7%), females (n = 42, 68.8%), and
      anonymous (n = 7, 11.5%) patients, with an age range of 19 to 45 years (average
      26.4), including 12 different ethnic groups representative of this region. Most
      patients were infected with a single genovar (82%), while 18% were co-infected
      with either two or three genovars. The 1156 bp-fragment of the ompA gene was
      sequenced in 46 samples to determine single nucleotide polymorphisms (SNP) among
      isolates. SNP-based subtyping and phylogenetic reconstruction revealed the
      presence of 13 variants of the ompA gene, such as E (E1, E2, E6), G (G1, G2, G3,
      G5), F1, K, D (D1, Da2), J1, and H2. Differing genovar distribution was
      identified among urban (E>G>F) and rural (E>K) populations, and in Slavic (E>G>D)
      and non-Slavic (E>G>K) ethnic groups. Multilocus sequence typing (MLST)
      determined five sequences types (STs), such as ST4 (56%, 95% confidence interval,
      CI, 70.0 to 41.3), ST6 (10%, 95% CI 21.8 to 3.3), ST9 (22%, 95% CI 35.9 to 11.5),
      ST10 (2%, 95% CI 10.7 to 0.05) and ST38 (10%, 95% CI 21.8 to 3.3). Thus, the most
      common STs were ST4 and ST9. CONCLUSION: C. trachomatis is a significant cause of
      morbidity among random heterosexual patients with genital chlamydial infections
      in the Saratov Region. Further studies should extend this investigation by
      describing trends in a larger population, both inside and outside of the Saratov
      Region to clarify some aspects for the actual application of C. trachomatis
      genotype analysis for disease control.

PMID- 29641544
TI  - A paucity of strategies for developing health literate organisations: A
      systematic review.
AB  - INTRODUCTION: People with low health literacy are more likely to delay seeking
      care and experience adverse outcomes. While health literacy is the product of
      individuals' capacities, it is also affected by the complexities of the health
      care system. System-level changes are needed to align health care demands better
      with the public's skills and abilities. We aimed to identify the evidence base
      for effective strategies for creating health literate organisations. METHODS: A
      systematic review and narrative synthesis of empirical studies was performed.
      Medline, Embase, PsychInfo and CINHAL databases were searched for empirical
      studies from OECD countries published from 2008 onwards, focusing on health
      literacy interventions at the organisational level. Analysis of the findings was
      informed by the National Academies' five-dimensional framework for the attributes
      of a health literate organisation, which include: organisational commitment,
      accessible education and technology infrastructure, augmented workforce, embedded
      policies and practices, and effective bidirectional communication. RESULTS: The
      title and abstract of 867 records were screened according to the selection
      criteria, leading to full text review of 125 articles. Seven studies were
      identified in the peer review literature. Adapting health literacy guidelines and
      tools was the most common approach to addressing organisational health literacy.
      CONCLUSION: While the use of health literacy tools proved important for raising
      awareness of health literacy issues within organisations, these tools were
      insufficient for generating the organisational changes necessary to improve
      organisational health literacy.

PMID- 29641545
TI  - Effects of genetic variants in the TSPO gene on protein structure and stability.
AB  - The 18 kDa translocator protein (TSPO) is an evolutionary conserved cholesterol
      binding protein localized in the outer mitochondrial membrane. Expression of TSPO
      is upregulated in activated microglia in various neuroinflammatory,
      neurodegenerative, and neoplastic disorders. Therefore, TSPO radioligands are
      used as biomarkers in positron emission tomography (PET) studies. In particular,
      a common A147T polymorphism in the TSPO gene affects binding of several high
      affinity TSPO radioligands. Given the relevance of TSPO as a diagnostic biomarker
      in disease processes, we systematically searched for mutations in the human TSPO
      gene by a wide array of evolution and structure based bioinformatics tools and
      identified potentially deleterious missense mutations. The two most frequently
      observed missense mutations A147T and R162H were further analysed in structural
      models of human wildtype and mutant TSPO proteins. The effects of missense
      mutations were studied on the atomic level using molecular dynamics simulations.
      To analyse putative effects of A147T and R162H variants on protein stability we
      established primary dermal fibroblast cultures from wt and homozygous A147T and
      R162H donors. Stability of endogenous TSPO protein, which is abundantly expressed
      in fibroblasts, was studied using cycloheximide protein degradation assay. Our
      data show that the A147T mutation significantly alters the flexibility and
      stability of the mutant protein. Furthermore both A147T and R162H mutations
      decreased the half-life of the mutant proteins by about 25 percent, which could
      in part explain its effect on reduced pregnenolone production and susceptibility
      to neuropsychiatric disorders. The present study is the first comprehensive
      bioinformatic analysis of genetic variants in the TSPO gene, thereby extending
      the knowledge about the clinical relevance of TSPO nsSNPs.

PMID- 29641546
TI  - Estimated hepatitis C prevalence and key population sizes in San Francisco: A
      foundation for elimination.
AB  - BACKGROUND: Initiated in 2016, End Hep C SF is a comprehensive initiative to
      eliminate hepatitis C (HCV) infection in San Francisco. The introduction of
      direct-acting antivirals to treat and cure HCV provides an opportunity for
      elimination. To properly measure progress, an estimate of baseline HCV
      prevalence, and of the number of people in various subpopulations with active HCV
      infection, is required to target and measure the impact of interventions. Our
      analysis was designed to incorporate multiple relevant data sources and estimate
      HCV burden for the San Francisco population as a whole, including specific key
      populations at higher risk of infection. METHODS: Our estimates are based on
      triangulation of data found in case registries, medical records, observational
      studies, and published literature from 2010 through 2017. We examined
      subpopulations based on sex, age and/or HCV risk group. When multiple sources of
      data were available for subpopulation estimates, we calculated a weighted average
      using inverse variance weighting. Credible ranges (CRs) were derived from 95%
      confidence intervals of population size and prevalence estimates. RESULTS: We
      estimate that 21,758 residents of San Francisco are HCV seropositive (CR: 10,274
      42,067), representing an overall seroprevalence of 2.5% (CR: 1.2%- 4.9%). Of
      these, 16,408 are estimated to be viremic (CR: 6,505-37,407), though this
      estimate includes treated cases; up to 12,257 of these (CR: 2,354-33,256) are
      people who are untreated and infectious. People who injected drugs in the last
      year represent 67.9% of viremic HCV infections. CONCLUSIONS: We estimated
      approximately 7,400 (51%) more HCV seropositive cases than are included in San
      Francisco's HCV surveillance case registry. Our estimate provides a useful
      baseline against which the impact of End Hep C SF can be measured.

PMID- 29641547
TI  - Production of xylitol and bio-detoxification of cocoa pod husk hemicellulose
      hydrolysate by Candida boidinii XM02G.
AB  - The use of cocoa pod husk hemicellulose hydrolysate (CPHHH) was evaluated for the
      production of xylitol by Candida boidinii XM02G yeast isolated from soil of cocoa
      growing areas and decaying bark, as an alternative means of reusing this type of
      waste. Xylitol was obtained in concentrations of 11.34 g.L-1, corresponding to a
      yield (Yp/s) of 0.52 g.g-1 with a fermentation efficiency (epsilon) of 56.6%. The
      yeast was tolerant to inhibitor compounds present in CPHHH without detoxification
      in different concentration factors, and was able to tolerate phenolic compounds
      at approximately 6 g.L-1. The yeast was also able to metabolize more than 99%
      (p/v) of furfural and hydroxymethylfurfural present in the non-detoxified CPHHH
      without extension of the cell-growth lag phase, showing the potential of this
      microorganism for the production of xylitol. The fermentation of cocoa pod husk
      hydrolysates appears to provide an alternative use which may reduce the impact
      generated by incorrect disposal of this waste.

PMID- 29641548
TI  - Multiple blood flow measurements before and after carotid artery stenting via
      phase-contrast magnetic resonance imaging: An observational study.
AB  - After carotid artery stenting, the procurement of information about blood flow
      redistribution among brain-feeding arteries and its time trend is essential to
      understanding a patient's physiological background and to determine their care
      regimen. Cerebral blood flow has been measured twice following carotid artery
      stenting in few previous studies, with some discrepancies in the results. The
      purpose of this study was to measure cerebral blood flow at multiple time points
      after carotid artery stenting, and to elucidate the time trend of cerebral blood
      flow and redistribution among arteries. Blood flow rates in 11 subjects were
      measured preoperatively, at one day, one week, and about three months,
      respectively after carotid artery stenting by using phase-contrast magnetic
      resonance imaging. The target vessels were the bilateral internal carotid
      arteries, the basilar artery, and the bilateral middle cerebral arteries. Lumen
      was semi-automatically defined using an algorithm utilizing pulsatility. The
      results showed that blood flow rates in the stented internal carotid artery and
      the ipsilateral middle cerebral artery increased following carotid artery
      stenting. Blood flow rates in the contralateral internal carotid artery and the
      basilar artery gradually declined, and they were lower than the preoperative
      values at three months after stenting. The sum of blood flow rates of the
      bilateral internal carotid arteries and the basilar artery increased after
      carotid artery stenting, and then decreased over the next three months. There was
      no significant change in the blood flow rate in the contralateral middle cerebral
      artery. From these results, it was concluded that redistribution among the
      bilateral internal carotid arteries and the basilar artery occurs after carotid
      artery stenting, and that it takes months thereafter to reach another
      equilibrium.

PMID- 29641550
TI  - Influence of transducer types on bone conduction hearing thresholds.
AB  - OBJECTIVE: Different types of bone conduction transducers with different physical
      and electro-acoustic properties are available for audiometric hearing threshold
      measurements. The reference equivalent threshold vibratory force levels (RETVFL)
      specified in ISO 389-3 are based on measurements conducted with the B71 and KH70
      transducers but apply to all types of transducers available for bone conduction
      audiometry. The objective of this study was to compare bone conduction hearing
      thresholds measured by different transducers. DESIGN: In a prospective study the
      hearing thresholds were measured psychometrically between 125 Hz and 8000 Hz
      using the Radioear B71, B81 and Pracitronic KH70 transducers. STUDY SAMPLE:
      Twenty-one normal hearing participants and fifteen hearing impaired participants.
      RESULTS: In both groups significant differences were found between the thresholds
      measured with the different transducers at the low frequencies 125 Hz and 250 Hz
      and the high frequencies 3000 Hz, 4000 Hz, 6000 Hz and 8000 Hz. In the normal
      hearing group, deviations from the reference threshold 0 dB HL towards lower
      thresholds were observed for the B71 and B81 at 125 Hz and at the high
      frequencies 3000 Hz, 4000 Hz, 6000 Hz and 8000 Hz. CONCLUSIONS: RETVFL-values
      should be reassessed and provided specifically for the different transducers.

PMID- 29641549
TI  - The flavonoid compound apigenin prevents colonic inflammation and motor
      dysfunctions associated with high fat diet-induced obesity.
AB  - BACKGROUND AND PURPOSE: Apigenin can exert beneficial actions in the prevention
      of obesity. However, its putative action on obesity-associated bowel motor
      dysfunctions is unknown. This study examined the effects of apigenin on colonic
      inflammatory and motor abnormalities in a mouse model of diet-induced obesity.
      EXPERIMENTAL APPROACH: Male C57BL/6J mice were fed with standard diet (SD) or
      high-fat diet (HFD). SD or HFD mice were treated with apigenin (10 mg/Kg/day).
      After 8 weeks, body and epididymal fat weight, as well as cholesterol,
      triglycerides and glucose levels were evaluated. Malondialdehyde (MDA), IL-1beta
      and IL-6 levels, and let-7f expression were also examined. Colonic infiltration
      by eosinophils, as well as substance P (SP) and inducible nitric oxide synthase
      (iNOS) expressions were evaluated. Motor responses elicited under blockade of NOS
      and tachykininergic contractions were recorded in vitro from colonic longitudinal
      muscle preparations. KEY RESULTS: When compared to SD mice, HFD animals displayed
      increased body weight, epididymal fat weight and metabolic indexes. HFD mice
      showed increments in colonic MDA, IL-1beta and IL-6 levels, as well as a decrease
      in let-7f expression in both colonic and epididymal tissues. HFD mice displayed
      an increase in colonic eosinophil infiltration. Immunohistochemistry revealed an
      increase in SP and iNOS expression in myenteric ganglia of HFD mice. In
      preparations from HFD mice, electrically evoked contractions upon NOS blockade or
      mediated by tachykininergic stimulation were enhanced. In HFD mice, Apigenin
      counteracted the increase in body and epididymal fat weight, as well as the
      alterations of metabolic indexes. Apigenin reduced also MDA, IL-1beta and IL-6
      colonic levels as well as eosinophil infiltration, SP and iNOS expression, along
      with a normalization of electrically evoked tachykininergic and nitrergic
      contractions. In addition, apigenin normalized let-7f expression in epididymal
      fat tissues, but not in colonic specimens. CONCLUSIONS AND IMPLICATIONS: Apigenin
      prevents systemic metabolic alterations, counteracts enteric inflammation and
      normalizes colonic dysmotility associated with obesity.

PMID- 29641551
TI  - Alterations in the vitamin D endocrine system during pregnancy: A longitudinal
      study of 855 healthy Norwegian women.
AB  - To ensure optimal calcium accrual in the fetal skeleton, a substantial rise
      occurs in 1,25-dihydroxyvitamin D (1,25(OH)2D), but is dependent on sufficient 25
      hydroxyvitamin (25(OH)D). Large longitudinal studies addressing free 25(OH)D and
      1,25(OH)2D during pregnancy are scarce. We aimed to assess levels of and
      relationship between 25(OH)D, 1,25(OH)2D, vitamin D-binding protein (DBP),
      parathyroid hormone (PTH), and free 25(OH)D during pregnancy; determinants of
      vitamin D status; and association between vitamin D indices or PTH and pregnancy
      outcomes (gestational diabetes mellitus and birthweight). Altogether 855 pregnant
      Norwegian Caucasian women from Trondheim and Stavanger (latitude 63 degrees N and
      58 degrees N) were recruited; 94 were lost to follow-up. The study was originally
      a randomized controlled trial (2007-2009) with gestational diabetes as primary
      outcome. Data were collected in second and third trimester. In third trimester,
      246 (34%) had vitamin D insufficiency and 52 (7%) deficiency (25(OH)D <50 and
      <30nmol/L, respectively). During wintertime in third trimester, 61 (47%) from
      Trondheim and 23 (51%) from Stavanger exhibited vitamin D insufficiency. PTH was
      elevated in 27 (3.7%). Estimate of change between trimesters was (95% CI):
      25(OH)D -1.8 (-2.8 to -0.7) nmol/L, DBP 0.62 (0.57 to 0.66) MUmol/L, calculated
      free 25(OH)D -1.7 (-2.0 to -1.4) pmol/L, PTH 0.81 (0.72 to 0.90) pmol/L,
      1,25(OH)2D (sub-analysis) 31.4 (CI 24.7 to 38.2) pmol/L. A decrease in 1,25(OH)2D
      occurred in 45% of those with vitamin D deficiency, and they also exhibited lower
      levels than women with adequate vitamin D status. No association of vitamin D
      indices and PTH with pregnancy outcomes was observed. Women in Trondheim
      displayed lower 25(OH)D levels, despite minor latitudinal differences. Less than
      one-fifth adhered to the authorities' vitamin D recommendations. These findings
      demonstrate that hypovitaminosis D is prevalent among pregnant women living in
      northern latitudes, especially during the dark season, and there is an unmet need
      to ensure adequate vitamin D intake.

PMID- 29641552
TI  - Coupled effects of oil spill and hurricane on saltmarsh terrestrial arthropods.
AB  - Terrestrial arthropods play an important role in saltmarsh ecosystems, mainly
      affecting the saltmarsh's primary production as the main consumers of terrestrial
      primary production and decomposition. Some of these arthropods, including
      selected insects and spiders, can be used as ecological indicators of overall
      marsh environmental health, as they are differentially sensitive to ecological
      stressors, such as land loss, erosion, oil spills, and tropical storms. In the
      present study, we used terrestrial arthropods collected from seven (three lightly
      oiled, four heavily-oiled) sites in Barataria Bay and from three unoiled
      reference sites in Delacroix, Louisiana, to determine the impacts of the
      distribution and re-distribution of Deepwater Horizon (DWH) oil on these
      saltmarsh ecosystems. A total of 9,476 and 12,256 insects were collected in 2013
      and 2014, respectively. The results show that the terrestrial arthropods were
      negatively affected by the re-distribution of DWH oil by Hurricane Isaac in 2012,
      although the level of impacts varied among the arthropod groups. Moreover, the
      mean diversity index was higher (>1.5) in 2014 than in 2013 (<1.5) for all sites,
      suggesting a recovery trajectory of the saltmarsh arthropod population. The
      higher taxonomic richness observed in the reference sites compared to the oiled
      sites for both years also indicated long-term impacts of DWH oil to the saltmarsh
      arthropod community. Whereas a slow recovery of certain terrestrial arthropods
      was observed, long-term monitoring of arthropod communities would help better
      understand the recovery and succession of the marsh ecosystems.

PMID- 29641553
TI  - AFLP-based genetic diversity of wild orchardgrass germplasm collections from
      Central Asia and Western China, and the relation to environmental factors.
AB  - Dactylis glomerata L. (orchardgrass) is an important perennial forage species in
      temperate areas of the world. It is usually used for silage, grazing and hay
      because of its high nutritional value and reproducibility. Central Asia, Xinjiang
      and Tibetan Plateau in China possess various special micro-environments that
      harbor many valuable resources, while different degrees of degradation of the
      grassland ecosystem occurred due to climatic changing and human activities.
      Investigating the genetic diversity of wild D. glomerat could provide basis for
      collection, protection, and utilization of some excellent germplasm resources.
      Totally 210 individuals from 14 populations-five from Xinjiang, two from Kangding
      (Tibetan Plateau), and seven from Central Asia were identified using AFLP
      technology. The average values of Nei's genetic diversity (Hj) and Shannon
      information index (Ho) were 0.383 and 0.394 respectively. UPGMA tree, STRUCTURE
      analysis and principal coordinate analysis (PCoA) showed populations from same
      region clustered together. AMOVA revealed 35.10% of the genetic differentiation
      (Fst) occurred among populations. Gene flow (Nm) was limited among all
      populations. Genetic diversity of D. glomerata was high but limited under
      isolation-by-distance pattern, resulting in high genetic differentiation and low
      gene flow among populations. Adjacent regions also exhibited similar results
      because of the barriers of high mountains. The environmental factors, such as
      precipitation, elevation, latitude and longitude also had some impacts on genetic
      diversity and structure pattern of populations.

PMID- 29641554
TI  - Constructing a consumption model of fine dining from the perspective of
      behavioral economics.
AB  - Numerous factors affect how people choose a fine dining restaurant, including
      food quality, service quality, food safety, and hedonic value. A conceptual
      framework for evaluating restaurant selection behavior has not yet been
      developed. This study surveyed 150 individuals with fine dining experience and
      proposed the use of mental accounting and axiomatic design to construct a
      consumer economic behavior model. Linear and logistic regressions were employed
      to determine model correlations and the probability of each factor affecting
      behavior. The most crucial factor was food quality, followed by service and
      dining motivation, particularly regarding family dining. Safe ingredients, high
      cooking standards, and menu innovation all increased the likelihood of consumers
      choosing fine dining restaurants.

PMID- 29641555
TI  - Two novel blood-based biomarker candidates measuring degradation of tau are
      associated with dementia: A prospective study.
AB  - BACKGROUND: Truncated tau appears to be specifically related to disease pathology
      and recent studies have shown the presence and elevation of several truncated tau
      species in Cerebrospinal fluid (CSF) of subjects with Alzheimer's disease (AD);
      however, the relevance of truncated Tau measurements in blood is still being
      studied. OBJECTIVE: The aim of the current study was to assess the longitudinal
      associations between baseline levels of two novel blood biomarker candidates
      measuring truncated tau, Tau-A and Tau-C, and the risk of incident dementia and
      AD in elderly women. METHODS: Using solid phase competitive ELISA, two tau
      fragments were detected in serum of 5,309 women from the Prospective
      Epidemiological Risk Factor study. The study was an observational, prospective
      study of Danish postmenopausal women. Subjects were followed with registry
      linkage for up to 15 years (median follow-up time 13.7 years). Cox regression was
      used to assess the utility of the biomarker candidates in relation to dementia
      and AD. RESULTS: High levels of Tau-A and Tau-C (above the median) in blood were
      associated with lower risk of dementia and AD (Tau-A: Dementia HR[95% CI] =
      0.85[0.70-1.04]; AD 0.71[0.52-0.98] and Tau-C: Dementia 0.84[0.70-1.00]; AD
      0.78[0.60-1.03]). Tau-C gave a very modest increase in the AUC in a 5-year
      prediction horizon as compared to a reference model with age and education, while
      a combination of the two did not improve their predictive capacity. CONCLUSIONS:
      Measurement of tau in serum is feasible. The serological tau turnover profile may
      be related to the diagnosis and development of dementia and AD. The exact
      processing and profile in serum in relation to cognitive disorders remains to be
      further assessed to provide simple non-invasive tests to identify subjects with
      progressive cognitive disorders.

PMID- 29641556
TI  - Anthropogenic contamination of tap water, beer, and sea salt.
AB  - Plastic pollution has been well documented in natural environments, including the
      open waters and sediments within lakes and rivers, the open ocean and even the
      air, but less attention has been paid to synthetic polymers in human consumables.
      Since multiple toxicity studies indicate risks to human health when plastic
      particles are ingested, more needs to be known about the presence and abundance
      of anthropogenic particles in human foods and beverages. This study investigates
      the presence of anthropogenic particles in 159 samples of globally sourced tap
      water, 12 brands of Laurentian Great Lakes beer, and 12 brands of commercial sea
      salt. Of the tap water samples analyzed, 81% were found to contain anthropogenic
      particles. The majority of these particles were fibers (98.3%) between 0.1-5 mm
      in length. The range was 0 to 61 particles/L, with an overall mean of 5.45
      particles/L. Anthropogenic debris was found in each brand of beer and salt. Of
      the extracted particles, over 99% were fibers. After adjusting for particles
      found in lab blanks for both salt and beer, the average number of particles found
      in beer was 4.05 particles/L with a range of 0 to 14.3 particles/L and the
      average number of particles found in each brand of salt was 212 particles/kg with
      a range of 46.7 to 806 particles/kg. Based on consumer guidelines, our results
      indicate the average person ingests over 5,800 particles of synthetic debris from
      these three sources annually, with the largest contribution coming from tap water
      (88%).

PMID- 29641557
TI  - Efficient minimization of multipole electrostatic potentials in torsion space.
AB  - The development of models of macromolecular electrostatics capable of delivering
      improved fidelity to quantum mechanical calculations is an active field of
      research in computational chemistry. Most molecular force field development takes
      place in the context of models with full Cartesian coordinate degrees of freedom.
      Nevertheless, a number of macromolecular modeling programs use a reduced set of
      conformational variables limited to rotatable bonds. Efficient algorithms for
      minimizing the energies of macromolecular systems with torsional degrees of
      freedom have been developed with the assumption that all atom-atom interaction
      potentials are isotropic. We describe novel modifications to address the
      anisotropy of higher order multipole terms while retaining the efficiency of
      these approaches. In addition, we present a treatment for obtaining derivatives
      of atom-centered tensors with respect to torsional degrees of freedom. We apply
      these results to enable minimization of the Amoeba multipole electrostatics
      potential in a system with torsional degrees of freedom, and validate the
      correctness of the gradients by comparison to finite difference approximations.
      In the interest of enabling a complete model of electrostatics with implicit
      treatment of solvent-mediated effects, we also derive expressions for the
      derivative of solvent accessible surface area with respect to torsional degrees
      of freedom.

PMID- 29641558
TI  - Detection of autoimmune antibodies in localized scleroderma by synthetic
      oligonucleotide antigens.
AB  - In this study, we developed a series of synthetic oligonucleotides that allowed
      us to investigate the details on the antigen recognition by autoimmune antibodies
      in localized scleroderma subjects. Besides dramatically improved analytical
      specificity of the assay, our data suggests a potential linking for antibodies to
      DNA to the biological status of disease state in localized scleroderma. Moreover,
      introducing chemical modifications into short synthetic deoxyribonucleic acid
      (DNA) and ribonucleic acid (RNA) molecules completely changed the binding titers
      of corresponding antibodies and their clinical relevance. The strongest observed
      effect was registered for the localized scleroderma skin damage index (LoSDI) on
      the IgG antibodies to TC dinucleotide-rich double-stranded antigen (p < 0.001).
      In addition to providing valuable tools for diagnosis of clinically relevant
      biomarkers, we believe that this work opens up new opportunities for research on
      antibodies to nucleic acids in localized scleroderma and other autoimmune
      diseases.

PMID- 29641560
TI  - Supramolecular assembly of the beta-catenin destruction complex and the effect of
      Wnt signaling on its localization, molecular size, and activity in vivo.
AB  - Wnt signaling provides a paradigm for cell-cell signals that regulate embryonic
      development and stem cell homeostasis and are inappropriately activated in
      cancers. The tumor suppressors APC and Axin form the core of the multiprotein
      destruction complex, which targets the Wnt-effector beta-catenin for
      phosphorylation, ubiquitination and destruction. Based on earlier work, we
      hypothesize that the destruction complex is a supramolecular entity that self
      assembles by Axin and APC polymerization, and that regulating assembly and
      stability of the destruction complex underlie its function. We tested this
      hypothesis in Drosophila embryos, a premier model of Wnt signaling. Combining
      biochemistry, genetic tools to manipulate Axin and APC2 levels, advanced imaging
      and molecule counting, we defined destruction complex assembly, stoichiometry,
      and localization in vivo, and its downregulation in response to Wnt signaling.
      Our findings challenge and revise current models of destruction complex function.
      Endogenous Axin and APC2 proteins and their antagonist Dishevelled accumulate at
      roughly similar levels, suggesting competition for binding may be critical. By
      expressing Axin:GFP at near endogenous levels we found that in the absence of Wnt
      signals, Axin and APC2 co-assemble into large cytoplasmic complexes containing
      tens to hundreds of Axin proteins. Wnt signals trigger recruitment of these to
      the membrane, while cytoplasmic Axin levels increase, suggesting altered
      assembly/disassembly. Glycogen synthase kinase3 regulates destruction complex
      recruitment to the membrane and release of Armadillo/beta-catenin from the
      destruction complex. Manipulating Axin or APC2 levels had no effect on
      destruction complex activity when Wnt signals were absent, but, surprisingly, had
      opposite effects on the destruction complex when Wnt signals were present.
      Elevating Axin made the complex more resistant to inactivation, while elevating
      APC2 levels enhanced inactivation. Our data suggest both absolute levels and the
      ratio of these two core components affect destruction complex function,
      supporting models in which competition among Axin partners determines destruction
      complex activity.

PMID- 29641559
TI  - DEC205-DC targeted DNA vaccine against CX3CR1 protects against atherogenesis in
      mice.
AB  - Studies disrupting the chemokine pathway CX3CL1 (fractalkine)/ CX3CR1 have shown
      decreased atherosclerosis in animal models but the techniques used to interrupt
      the pathway have not been easily translatable into human trials. DNA vaccination
      potentially overcomes the translational difficulties. We evaluated the effect of
      a DNA vaccine, targeted to CX3CR1, on atherosclerosis in a murine model and
      examined possible mechanisms of action. DNA vaccination against CX3CR1, enhanced
      by dendritic cell targeting using DEC-205 single chain variable region fragment
      (scFv), was performed in 8 week old ApoE-/- mice, fed a normal chow diet. High
      levels of anti-CX3CR1 antibodies were induced in vaccinated mice. There were no
      apparent adverse reactions to the vaccine. Arterial vessels of 34 week old mice
      were examined histologically for atherosclerotic plaque size, macrophage
      infiltration, smooth muscle cell infiltration and lipid deposition. Vaccinated
      mice had significantly reduced atherosclerotic plaque in the brachiocephalic
      artery. There was less macrophage infiltration but no significant change to the
      macrophage phenotype in the plaques. There was less lipid deposition in the
      lesions, but there was no effect on smooth muscle cell migration. Targeted DNA
      vaccination to CX3CR1 was well tolerated, induced a strong immune response and
      resulted in attenuated atherosclerotic lesions with reduced macrophage
      infiltration. DNA vaccination against chemokine pathways potentially offers a
      potential therapeutic option for the treatment of atherosclerosis.

PMID- 29641561
TI  - Discovery of genetic variants of the kinases that activate tenofovir among
      individuals in the United States, Thailand, and South Africa: HPTN067.
AB  - Tenofovir (TFV), a nucleotide reverse transcriptase inhibitor, requires two
      phosphorylation steps to form a competitive inhibitor of HIV reverse
      transcriptase. Adenylate kinase 2 (AK2) has been previously demonstrated to
      phosphorylate tenofovir to tenofovir-monophosphate, while creatine kinase, muscle
      (CKM), pyruvate kinase, muscle (PKM) and pyruvate kinase, liver and red blood
      cell (PKLR) each have been found to phosphorylate tenofovir-monophosphate to the
      pharmacologically active tenofovir-diphosphate. In the present study, genomic DNA
      isolated from dried blood spots collected from 505 participants from Bangkok,
      Thailand; Cape Town, South Africa; and New York City, USA were examined for
      variants in AK2, CKM, PKM, and PKLR using next-generation sequencing. The
      bioinformatics tools SIFT and PolyPhen predicted that 19 of the 505 individuals
      (3.7% frequency) carried variants in at least one kinase that would result in a
      decrease or loss of enzymatic activity. To functionally test these predictions,
      AK2 and AK2 variants were expressed in and purified from E. coli, followed by
      investigation of their activities towards tenofovir. Interestingly, we found that
      purified AK2 had the ability to phosphorylate tenofovir-monophosphate to
      tenofovir-diphosphate in addition to phosphorylating tenofovir to tenofovir
      monophosphate. Further, four of the six AK2 variants predicted to result in a
      loss or decrease of enzyme function exhibited a >=30% decrease in activity
      towards tenofovir in our in vitro assays. Of note, an AK2 K28R variant resulted
      in a 72% and 81% decrease in the formation of tenofovir-monophosphate and
      tenofovir-diphosphate, respectively. These data suggest that there are naturally
      occurring genetic variants that could potentially impact TFV activation.

PMID- 29641562
TI  - Suppression of the pelo protein by Wolbachia and its effect on dengue virus in
      Aedes aegypti.
AB  - The endosymbiont Wolbachia is known to block replication of several important
      arboviruses, including dengue virus (DENV), in the mosquito vector Aedes aegypti.
      So far, the exact mechanism of this viral inhibition is not fully understood. A
      recent study in Drosophila melanogaster has demonstrated an interaction between
      the pelo gene and Drosophila C virus. In this study, we explored the possible
      involvement of the pelo protein, that is involved in protein translation, in
      Wolbachia-mediated antiviral response and mosquito-DENV interaction. We found
      that pelo is upregulated during DENV replication and its silencing leads to
      reduced DENV virion production suggesting that it facilities DENV replication.
      However, in the presence of Wolbachia, specifically in female mosquitoes, the
      pelo protein is downregulated and its subcellular localization is altered, which
      could contribute to reduction in DENV replication in Ae. aegypti. In addition, we
      show that the microRNA aae-miR-2940-5p, whose abundance is highly enriched in
      Wolbachia-infected mosquitoes, might mediate regulation of pelo. Our data reveals
      identification of pelo as a host factor that is positively involved in DENV
      replication, and its suppression in the presence of Wolbachia may contribute to
      virus blocking exhibited by the endosymbiont.

PMID- 29641563
TI  - Attitudes towards and knowledge about Human Papillomavirus (HPV) and the HPV
      vaccination in parents of teenage boys in the UK.
AB  - The incidence of cancers attributable to Human Papillomavirus (HPV) that affect
      males is on the rise. Currently in the UK teenage boys are not vaccinated against
      HPV while teenage girls are. The rationale for not vaccinating boys is that
      vaccinating girls should provide herd immunity to boys, however this does not
      protect men who have sex with men or men who have sex with unvaccinated women.
      The issue of whether to vaccinate boys or not is a controversial one with
      considerable lobbying taking place to change the existing policy. On one side of
      the debate are financial considerations while on the other side health equality
      is important. One avenue that has not been presented is the parental perspective.
      The current study uses a self-report questionnaire to explore what parents of
      teenage boys know about HPV and the vaccine and whether they want the vaccine for
      their sons. Only half of the parents had heard of HPV prior to completing the
      survey. Of those who had heard of HPV, knowledge about the health sequelae of HPV
      for men was poor relative to their knowledge about its impact on female health.
      Parents who would be willing to vaccinate their sons had higher levels of
      knowledge about HPV than those parents who would be unwilling or unsure.
      Irrespective of whether they had previously heard of HPV or not, once provided
      with a brief description of HPV, the majority of parents thought that boys should
      be offered the vaccination. There is a pressing need for public education about
      the potential impact of HPV on male health in order to facilitate uptake of the
      vaccine in the event of the vaccination programme being extended to men or to
      facilitate informed decision making about seeking the vaccine privately in the
      event that it isn't.

PMID- 29641564
TI  - Matching optical flow to motor speed in virtual reality while running on a
      treadmill.
AB  - We investigated how visual and kinaesthetic/efferent information is integrated
      for speed perception in running. Twelve moderately trained to trained subjects
      ran on a treadmill at three different speeds (8, 10, 12 km/h) in front of a
      moving virtual scene. They were asked to match the visual speed of the scene to
      their running speed-i.e., treadmill's speed. For each trial, participants
      indicated whether the scene was moving slower or faster than they were running.
      Visual speed was adjusted according to their response using a staircase until the
      Point of Subjective Equality (PSE) was reached, i.e., until visual and running
      speed were perceived as equivalent. For all three running speeds, participants
      systematically underestimated the visual speed relative to their actual running
      speed. Indeed, the speed of the visual scene had to exceed the actual running
      speed in order to be perceived as equivalent to the treadmill speed. The
      underestimation of visual speed was speed-dependent, and percentage of
      underestimation relative to running speed ranged from 15% at 8km/h to 31% at
      12km/h. We suggest that this fact should be taken into consideration to improve
      the design of attractive treadmill-mediated virtual environments enhancing
      engagement into physical activity for healthier lifestyles and disease prevention
      and care.

PMID- 29641565
TI  - Deletion of pro-angiogenic factor vasohibin-2 ameliorates glomerular alterations
      in a mouse diabetic nephropathy model.
AB  - Angiogenesis has been implicated in glomerular alterations in the early stage of
      diabetic nephropathy. We previously reported the renoprotective effects of
      vasohibin-1 (VASH1), which is a novel angiogenesis inhibitor derived from
      endothelial cells, on diabetic nephropathy progression. Vasohibin-2 (VASH2) was
      originally identified as a VASH1 homolog and possesses pro-angiogenic activity in
      contrast to VASH1. In addition, VASH2 was recently shown to promote epithelial-to
      mesenchymal transition via enhanced transforming growth factor (TGF)-beta
      signaling in cancer cells. Herein, we investigated the pathogenic roles of VASH2
      in diabetic nephropathy using VAHS2-deficient mice. The type 1 diabetes model was
      induced by intraperitoneal injections of streptozotocin in VASH2 homozygous
      knockout (VASH2LacZ/LacZ) or wild-type mice. These mice were euthanized 16 weeks
      after inducing hyperglycemia. Increased urine albumin excretion and creatinine
      clearance observed in diabetic wild-type mice were significantly prevented in
      diabetic VASH2-deficient mice. Accordingly, diabetes-induced increase in
      glomerular volume and reduction in glomerular slit-diaphragm density were
      significantly improved in VASH2 knockout mice. Increased glomerular endothelial
      area was also suppressed in VASH2-deficient mice, in association with inhibition
      of enhanced vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2), but
      not VEGF level. Furthermore, glomerular accumulation of mesangial matrix,
      including type IV collagen, and increased expression of TGF-beta were improved in
      diabetic VASH2 knockout mice compared with diabetic wild-type mice. Based on the
      immunofluorescence findings, endogenous VASH2 localization in glomeruli was
      consistent with mesangial cells. Human mesangial cells (HMCs) were cultured under
      high glucose condition in in vitro experiments. Transfection of VASH2 small
      interfering RNA (siRNA) into the HMCs resulted in the suppression of type IV
      collagen production induced by high glucose compared with control siRNA. These
      results indicate that VASH2 may be involved in diabetes-induced glomerular
      alterations, particularly impaired filtration barrier and mesangial expansion.
      Therefore, VASH2 is likely to represent a promising therapeutic target for
      diabetic nephropathy.

PMID- 29641566
TI  - Indirect treatment comparison of cabazitaxel for patients with metastatic
      castrate-resistant prostate cancer who have been previously treated with a
      docetaxel-containing regimen.
AB  - BACKGROUND: The objective of this study was to conduct an indirect treatment
      comparison between cabazitaxel, abiraterone and enzalutamide to determine the
      clinical efficacy and safety of cabazitaxel relative to comparators in the
      treatment of patients with metastatic castrate-resistant prostate cancer who
      progress on docetaxel-based therapies. METHODS: A systematic literature review
      was conducted to inform the network meta-analysis of cabazitaxel, abiraterone and
      enzalutamide. Due to a lack of head-to-head trials, studies with a comparator arm
      of best supportive care were included in the analysis. Overall survival,
      progression-free survival, and adverse events were compared within both Bayesian
      and Frequentist frameworks. The ratios for survival outcomes were estimated using
      hazard ratios (HR), and the ratios for adverse events between groups were
      estimated using odds ratios (ORs); uncertainty was reported as 95% confidence
      (Frequentist) and credible (Baysesian) Intervals. RESULTS: Three of thirteen
      trials identified for abstraction were relevant for analyses. Median overall
      survival was not statistically significantly different for abiraterone (HR =
      1.04; 95% CI = 0.83-1.28) or enzalutamide (HR = 0.88; 95% CI = 0.69-1.11) when
      compared to cabazitaxel in the Bayesian analysis. Anaemia (OR = 3.71; 95% CI =
      1.01-10.44), diarrhoea (OR = 16.60; 95% CI = 1.41-75.31) and haematuria (OR =
      3.88; 95% CI = 1.03-10.09) were more likely to occur in the cabazitaxel group
      than the abiraterone group, while pyrexia risk was higher in cabazitaxel compared
      to enzalutamide (OR = 36.23; 95% CI = 1.14-206.40). Frequentist analyses produced
      similar results. CONCLUSIONS: The scarcity of clinical studies and lack of a
      common comparator limited analyses. The adverse event results must be interpreted
      with caution as many were based on small numbers. The results from this analysis
      indicate comparable survival outcomes and adverse event profiles. As these
      pivotal studies may not reflect the contemporary treatment landscape and patient
      profiles, additional research, including head-to-head clinical trials and real
      world observational studies, should be conducted to further elucidate the
      beneficial effects of these therapies.

PMID- 29641567
TI  - Use of capillary Western immunoassay (Wes) for quantification of dystrophin
      levels in skeletal muscle of healthy controls and individuals with Becker and
      Duchenne muscular dystrophy.
AB  - Duchenne muscular dystrophy (DMD) is a neuromuscular disease characterized by
      progressive weakness of the skeletal and cardiac muscles. This X-linked disorder
      is caused by open reading frame disrupting mutations in the DMD gene, resulting
      in strong reduction or complete absence of dystrophin protein. In order to use
      dystrophin as a supportive or even surrogate biomarker in clinical studies on
      investigational drugs aiming at correcting the primary cause of the disease, the
      ability to reliably quantify dystrophin expression in muscle biopsies of DMD
      patients pre- and post-treatment is essential. Here we demonstrate the
      application of the ProteinSimple capillary immunoassay (Wes) method, a gel- and
      blot-free method requiring less sample, antibody and time to run than
      conventional Western blot assay. We optimized dystrophin quantification by Wes
      using 2 different antibodies and found it to be highly sensitive, reproducible
      and quantitative over a large dynamic range. Using a healthy control muscle
      sample as a reference and alpha-actinin as a protein loading/muscle content
      control, a panel of skeletal muscle samples consisting of 31 healthy controls, 25
      Becker Muscle dystrophy (BMD) and 17 DMD samples was subjected to Wes analysis.
      In healthy controls dystrophin levels varied 3 to 5-fold between the highest and
      lowest muscle samples, with the reference sample representing the average of all
      31 samples. In BMD muscle samples dystrophin levels ranged from 10% to 90%, with
      an average of 33% of the healthy muscle average, while for the DMD samples the
      average dystrophin level was 1.3%, ranging from 0.7% to 7% of the healthy muscle
      average. In conclusion, Wes is a suitable, efficient and reliable method for
      quantification of dystrophin expression as a biomarker in DMD clinical drug
      development.

PMID- 29641568
TI  - The physiological cost of diazotrophy for Trichodesmium erythraeum IMS101.
AB  - Trichodesmium plays a significant role in the oligotrophic oceans, fixing
      nitrogen in an area corresponding to half of the Earth's surface, representing up
      to 50% of new production in some oligotrophic tropical and subtropical oceans.
      Whilst Trichodesmium blooms at the surface exhibit a strong dependence on
      diazotrophy, colonies at depth or at the surface after a mixing event could be
      utilising additional N-sources. We conducted experiments to establish how
      acclimation to varying N-sources affects the growth, elemental composition, light
      absorption coefficient, N2 fixation, PSII electron transport rate and the
      relationship between net and gross photosynthetic O2 exchange in T. erythraeum
      IMS101. To do this, cultures were acclimated to growth medium containing NH4+ and
      NO3- (replete concentrations) or N2 only (diazotrophic control). The light
      dependencies of O2 evolution and O2 uptake were measured using membrane inlet
      mass spectrometry (MIMS), while PSII electron transport rates were measured from
      fluorescence light curves (FLCs). We found that at a saturating light intensity,
      Trichodesmium growth was ~ 10% and 13% lower when grown on N2 than with NH4+ and
      NO3-, respectively. Oxygen uptake increased linearly with net photosynthesis
      across all light intensities ranging from darkness to 1100 MUmol photons m-2 s-1.
      The maximum rates and initial slopes of light response curves for C-specific
      gross and net photosynthesis and the slope of the relationship between gross and
      net photosynthesis increased significantly under non-diazotrophic conditions. We
      attribute these observations to a reduced expenditure of reductant and ATP for
      nitrogenase activity under non-diazotrophic conditions which allows NADPH and ATP
      to be re-directed to CO2 fixation and/or biosynthesis. The energy and reductant
      conserved through utilising additional N-sources could enhance Trichodesmium's
      productivity and growth and have major implications for its role in ocean C and N
      cycles.

PMID- 29641569
TI  - Optimization of the cydex blue assay: A one-step colorimetric protein assay using
      cyclodextrins and compatible with detergents and reducers.
AB  - Sodium dodecyl sulfate electrophoresis (SDS) is a protein separation technique
      widely used, for example, prior to immunoblotting. Samples are usually prepared
      in a buffer containing both high concentrations of reducers and high
      concentrations of SDS. This conjunction renders the samples incompatible with
      common protein assays. By chelating the SDS, cyclodextrins make the use of
      simple, dye-based colorimetric assays possible. In this paper, we describe the
      optimization of the assay, focussing on the cyclodextrin/SDS ratio and the use of
      commercial assay reagents. The adaptation of the assay to a microplate format and
      using other detergent-containing conventional extraction buffers is also
      described.

PMID- 29641570
TI  - Identification of entomopathogenic nematodes and symbiotic bacteria from Nam Nao
      National Park in Thailand and larvicidal activity of symbiotic bacteria against
      Aedes aegypti and Aedes albopictus.
AB  - Entomopathogenic nematodes (EPNs) that are symbiotically associated with
      Xenorhabdus and Photorhabdus bacteria can kill target insects via direct
      infection and toxin action. There are limited reports identifying such organisms
      in the National Park of Thailand. Therefore, the objectives of this study were to
      identify EPNs and symbiotic bacteria from Nam Nao National Park, Phetchabun
      Province, Thailand and to evaluate the larvicidal activity of bacteria against
      Aedes aegypti and Ae. albopictus. A total of 12 EPN isolates belonging to
      Steinernema and Heterorhabditis were obtained form 940 soil samples between
      February 2014 and July 2016. EPNs were molecularly identified as S. websteri (10
      isolates) and H. baujardi (2 isolates). Symbiotic bacteria were isolated from
      EPNs and molecularly identified as P. luminescens subsp. akhurstii (13 isolates),
      X. stockiae (11 isolates), X. vietnamensis (2 isolates) and X. japonica (1
      isolate). For the bioassay, bacterial suspensions were evaluated for toxicity
      against third to early fourth instar larvae of Aedes spp. The larvae of both
      Aedes species were orally susceptible to symbiotic bacteria. The highest larval
      mortality of Ae. aegypti was 99% after exposure to X. stockiae (bNN112.3_TH) at
      96 h, and the highest mortality of Ae. albopictus was 98% after exposure to P.
      luminescens subsp. akhurstii (bNN121.4_TH) at 96 h. In contrast to the control
      groups (Escherichia coli and distilled water), the mortality rate of both
      mosquito larvae ranged between 0 and 7% at 72 h. Here, we report the first
      observation of X. vietnamensis in Thailand. Additionally, we report the first
      observation of P. luminescens subsp. akhurstii associated with H. baujardi in
      Thailand. X. stockiae has potential to be a biocontrol agent for mosquitoes. This
      investigation provides a survey of the basic diversity of EPNs and symbiotic
      bacteria in the National Park of Thailand, and it is a bacterial resource for
      further studies of bioactive compounds.

PMID- 29641571
TI  - Still reduced cardiovascular mortality 12 years after supplementation with
      selenium and coenzyme Q10 for four years: A validation of previous 10-year follow
      up results of a prospective randomized double-blind placebo-controlled trial in
      elderly.
AB  - BACKGROUND: Selenium and coenzyme Q10 are both necessary for optimal cell
      function in the body. The intake of selenium is low in Europe, and the endogenous
      production of coenzyme Q10 decreases as age increases. Therefore, an intervention
      trial using selenium and coenzyme Q10 for four years as a dietary supplement was
      performed. The main publication reported reduced cardiovascular mortality as a
      result of the intervention. In the present sub-study the objective was to
      determine whether reduced cardiovascular (CV) mortality persisted after 12 years,
      in the supplemented population or in subgroups with diabetes, hypertension,
      ischemic heart disease or reduced functional capacity due to impaired cardiac
      function. METHODS: From a rural municipality in Sweden, four hundred forty-three
      healthy elderly individuals were included. All cardiovascular mortality was
      registered, and no participant was lost to the follow-up. Based on death
      certificates and autopsy results, mortality was registered. FINDINGS: After 12
      years a significantly reduced CV mortality could be seen in those supplemented
      with selenium and coenzyme Q10, with a CV mortality of 28.1% in the active
      treatment group, and 38.7% in the placebo group. A multivariate Cox regression
      analysis demonstrated a reduced CV mortality risk in the active treatment group
      (HR: 0.59; 95%CI 0.42-0.81; P = 0.001). In those with ischemic heart disease,
      diabetes, hypertension and impaired functional capacity we demonstrated a
      significantly reduced CV mortality risk. CONCLUSIONS: This is a 12-year follow-up
      of a group of healthy elderly participants that were supplemented with selenium
      and coenzyme Q10 for four years. Even after twelve years we observed a
      significantly reduced risk for CV mortality in this group, as well as in
      subgroups of patients with diabetes, hypertension, ischemic heart disease or
      impaired functional capacity. The results thus validate the results obtained in
      the 10-year evaluation. The protective action was not confined to the
      intervention period, but persisted during the follow-up period. The mechanisms
      behind this effect remain to be fully elucidated, although various effects on
      cardiac function, oxidative stress, fibrosis and inflammation have previously
      been identified. Since this was a small study, the observations should be
      regarded as hypothesis-generating. TRIAL REGISTRATION: Clinicaltrials.gov
      NCT01443780.

PMID- 29641572
TI  - The Trier Social Stress Test and the Trier Social Stress Test for groups:
      Qualitative investigations.
AB  - The Trier Social Stress Test (TSST) and its version for groups (TSST-G) are the
      gold standard for inducing acute psychosocial stress in human experimental
      settings and have been used in numerous studies since the early 1990s. The TSST
      and the TSST-G lead to effects on different physiological and psychological
      markers, such as salivary cortisol, anxiety, and emotional states. These effects
      were assessed with quantitative methods comparing pre-test and post-test measures
      with statistical analyses. But to date, no qualitative analyses have been
      conducted to examine the meaningful experience of participants during the TSST
      and the TSST-G. This study is the first to conduct qualitative investigations to
      further clarify the stressful experience of participants confronted with these
      procedures. Preliminary results showed as expected that the TSST and the TSST-G
      effectively induced psychosocial stress, with cortisol levels, cognitive anxiety,
      somatic anxiety, and arousal increases, and with pleasure and dominance
      decreases. At the qualitative level, the results evidenced that the two
      theoretically stressful components of the TSST and the TSST-G, namely social
      evaluative threat and uncontrollability, were experienced as stress-inducing by
      the participants. Two case studies confirmed these findings. But the results also
      showed on one hand that psychosocial stress is a dynamic phenomenon, with
      important fluctuations throughout the tasks (mainly for the TSST-G); and on the
      other hand that despite the similar physiological and psychological responses
      between the TSST and the TSST-G evidenced by the literature, the experience of
      the participants was both similar and specific. Use of a qualitative method
      allowed us to provide a complementary point of view to understand the meaningful
      experience of participants during these stressful procedures, apprehending the
      dynamic of the subjective stress experience without disrupting it.

PMID- 29641574
TI  - Correction: Prospective mental imagery as its link with anxiety and depression in
      prisoners.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0191551.].

PMID- 29641573
TI  - Systematic evaluation of a targeted gene capture sequencing panel for molecular
      diagnosis of retinitis pigmentosa.
AB  - BACKGROUND: Inherited eye diseases are major causes of vision loss in both
      children and adults. Inherited eye diseases are characterized by clinical
      variability and pronounced genetic heterogeneity. Genetic testing may provide an
      accurate diagnosis for ophthalmic genetic disorders and allow gene therapy for
      specific diseases. METHODS: A targeted gene capture panel was designed to capture
      exons of 283 inherited eye disease genes including 58 known causative retinitis
      pigmentosa (RP) genes. 180 samples were tested with this panel, 68 were
      previously tested by Sanger sequencing. Systematic evaluation of our method and
      comprehensive molecular diagnosis were carried on 99 RP patients. RESULTS: 96.85%
      targeted regions were covered by at least 20 folds, the accuracy of variants
      detection was 99.994%. In 4 of the 68 samples previously tested by Sanger
      sequencing, mutations of other diseases not consisting with the clinical
      diagnosis were detected by next-generation sequencing (NGS) not Sanger. Among the
      99 RP patients, 64 (64.6%) were detected with pathogenic mutations, while in 3
      patients, it was inconsistent between molecular diagnosis and their initial
      clinical diagnosis. After revisiting, one patient's clinical diagnosis was
      reclassified. In addition, 3 patients were found carrying large deletions.
      CONCLUSIONS: We have systematically evaluated our method and compared it with
      Sanger sequencing, and have identified a large number of novel mutations in a
      cohort of 99 RP patients. The results showed a sufficient accuracy of our method
      and suggested the importance of molecular diagnosis in clinical diagnosis.

PMID- 29641575
TI  - Molecular engineering of the salicylate-inducible transcription factor Sal7AR for
      orthogonal and high gene expression in Escherichia coli.
AB  - I have previously identified a metagenomic fragment (~4 kb) containing the
      salicylate (2-hydroxybenzoate)-responsive transcriptional regulator Sal7AR.
      Taking advantage of the inert nature of salicylate to common genetic switches
      used in Escherichia coli, here I developed a salicylate-inducible high expression
      system in E. coli. I first applied a deletion analysis to the metagenomic
      fragment to identify the core region (~1 kb) necessary for the salicylate
      dependent expression. Sal7AR was subjected to an error-prone PCR, and a library
      was screened for an enhanced expression of a reporter green fluorescent protein
      (GFP) gene in the presence of 1 mM salicylate, where virtually no growth
      inhibition was observed. Three beneficial amino acid substitutions were
      identified (N282K, Q292R, and V295G), each of which improved the expression of
      GFP relative to the wildtype by several-fold. The three sites were then
      completely randomized by saturation mutagenesis either individually or
      combinatorially to identify three variants carrying a single point mutation,
      N282L, V295F, or V295S; no further improvements were observed by combining these
      mutations. Salicylate-dependent expression of these mutants was highly repressed
      in its absence and escalated in response to ~10 MUM salicylate, and gradually
      increased up to 1 mM salicylate; the induction rate was approximately 15 times
      greater than that achieved with a lactose promoter. Orthogonality to the lactose
      based expression system was also confirmed. This salicylate-based expression
      system should thus be advantageously used for high-level production of
      recombinant proteins in combination with common lactose-dependent induction
      systems.

PMID- 29641576
TI  - Unacceptable treatment outcomes and associated factors among India's initial
      cohorts of multidrug-resistant tuberculosis (MDR-TB) patients under the revised
      national TB control programme (2007-2011): Evidence leading to policy
      enhancement.
AB  - BACKGROUND: Globally, India has the world's highest burden of multidrug-resistant
      tuberculosis (MDR-TB). Programmatic Management of Drug Resistant TB (PMDT) in
      India began in 2007 and nationwide coverage was achieved in early 2013. Poor
      initial microbiological outcomes under the Revised National Tuberculosis Control
      Programme (RNTCP) prompted detailed analysis. This is the first study on factors
      significantly associated with poor outcomes in MDR-TB patients treated under the
      RNTCP. OBJECTIVE: To evaluate initial sputum culture conversion, culture
      reversion and final treatment outcomes among MDR-TB patients registered in India
      from 2007 to early 2011 who were treated with a standard 24-month regimen under
      daily-observed treatment. METHODS: This is a retrospective cohort study. Clinical
      and microbiological data were abstracted from PMDT records. Initial sputum
      culture conversion, culture reversion and treatment outcomes were defined by
      country adaptation of the standard WHO definitions (2008). Cox proportional
      hazards modeling with logistic regression, multinomial logistic regression and
      adjusted odds ratio was used to evaluate factors associated with interim and
      final outcomes respectively, controlling for demographic and clinical
      characteristics. RESULTS: In the cohort of 3712 MDR-TB patients, 2735 (73.6%) had
      initial sputum culture conversion at 100 median days (IQR 92-125), of which 506
      (18.5%) had culture reversion at 279 median days (IQR 202-381). Treatment
      outcomes were available for 2264 (60.9%) patients while 1448 (39.0%) patients
      were still on treatment or yet to have a definite outcome at the time of
      analysis. Of 2264 patients, 781 (34.5%) had treatment success, 644 (28.4%) died,
      670 (29.6%) were lost to follow up, 169 (7.5%) experienced treatment failure or
      were changed to XDR-TB treatment. Factors significantly associated with either
      culture non-conversion, culture reversion and/or unfavorable treatment outcomes
      were baseline BMI < 18; >= seven missed doses in intensive phase (IP) and
      continuation phase (CP); cavitary disease; prior treatment episodes characterized
      by re-treatment regimen taken twice, longer duration and more episodes of
      treatment; any weight loss during treatment; males and additional resistance to
      first line drugs (Ethambutol, Streptomycin). In a subgroup of 104 MDR-TB
      patients, 62 (59.6%) had Ofloxacin resistance among whom only 25.8% had treatment
      success, half of the success (54.8%) seen in Ofloxacin sensitive patients.
      Baseline susceptibility to Ofloxacin (HR 2.04) and Kanamycin (HR 4.55)
      significantly doubled and quadrupled the chances for culture conversion
      respectively while baseline susceptibility to Ofloxacin (AOR 0.37) also
      significantly reduced the odds of unfavorable treatment outcomes (p value <=0.05)
      in multinomial logistic regression model. CONCLUSION: India's initial MDR-TB
      patients' cohort treated under the RNTCP experienced poor treatment outcomes. To
      address the factors associated with poor treatment outcomes revealed in our
      study, a systematic multi-pronged approach would be needed. A series of policies
      and interventions have been developed to address these factors to improve DR-TB
      treatment outcomes and are being scaled-up in India.

PMID- 29641577
TI  - Shared larval rearing environment, sex, female size and genetic diversity shape
      Ae. albopictus bacterial microbiota.
AB  - The Asian tiger mosquito Aedes albopictus became of public health concern as it
      can replicate and transmit viral and filarial pathogens with a strong invasive
      success over the world. Various strategies have been proposed to reduce mosquito
      population's vectorial capacity. Among them, symbiotic control of mosquito borne
      disease offers promising perspectives. Such method is likely to be affected by
      the dynamics of mosquito-associated symbiotic communities, which might in turn be
      affected by host genotype and environment. Our previous study suggested a
      correlation between mosquitoes' origin, genetic diversity and midgut bacterial
      diversity. To distinguish the impact of those factors, we have been studying the
      midgut bacterial microbiota of two Ae. albopictus populations from tropical (La
      Reunion) and temperate (Montpellier) origins under controlled laboratory
      conditions. the two populations experienced random mating or genetic bottleneck.
      Microbiota composition did not highlight any variation of the alpha and beta
      diversities in bacterial communities related to host's populations. However,
      sizes of the mosquitoes were negatively correlated with the bacterial alpha
      diversity of females. Variations in mosquito sex were associated with a shift in
      the composition of bacterial microbiota. The females' mosquitoes also exhibited
      changes in the microbiota composition according to their size and after
      experiencing a reduction of their genetic diversity. These results provide a
      framework to investigate the impact of population dynamics on the symbiotic
      communities associated with the tiger mosquito.

PMID- 29641578
TI  - Influence of clinicopathological characteristics and comprehensive treatment
      models on the prognosis of small cell carcinoma of the cervix: A systematic
      review and meta-analysis.
AB  - Small cell carcinoma of the cervix (SCCC) is a rare primary neuroendocrine
      cervical carcinoma with a high degree of invasiveness. SCCC is prone to early
      stage lymph node and distant metastases and characterized by a poor prognosis.
      Currently, there is no standard treatment. This study aimed to evaluate the
      clinicopathological factors and treatment models that influence SCCC prognosis
      through a systematic review and meta-analysis, to improve the diagnosis and
      treatment of SCCC. A comprehensive search was performed in multiple medical
      literature databases to retrieve studies on the clinical prognosis of SCCC
      published in China and abroad as of March 1, 2017. Twenty cohort studies with
      1904 patients were analyzed. Meta-analysis showed statistical significance for
      the following factors: FIGO staging (hazard ratio [HR] = 2.63, 95% confidence
      interval [CI]: 2.13-3.24; odds ratio [OR] = 3.72, 95% CI: 2.46-5.62), tumor size
      (HR = 1.64, 95% CI: 1.25-2.15), parametrial involvement (HR = 2.40, 95% CI: 1.43
      4.05), resection margin (HR = 4.09, 95% CI: 2.27-7.39), lymph node metastasis (OR
      = 2.09, 95% CI: 1.18-3.71), depth of stromal invasion (HR = 1.99, 95% CI: 1.33
      2.97), neoadjuvant chemotherapy (HR = 2.06, 95% CI: 1.14-3.73), and adjuvant
      chemotherapy (HR = 1.63, 95% CI: 1.26-2.12; OR = 1.48, 95% CI: 1.02-2.16). FIGO
      staging, tumor size, parametrial involvement, resection margin, depth of stromal
      invasion, and lymph node metastasis can be used as clinicopathological
      characteristics for the prediction of SCCC prognosis. Neoadjuvant chemotherapy
      tended to improve prognosis. Our findings suggest that neoadjuvant chemotherapy
      plus adjuvant chemotherapy may be the preferred strategy. However, adjuvant
      radiotherapy appeared to cause no significant improvement in prognosis.
      Therefore, the clinical application of radiotherapy and the relationship between
      radiotherapy and clinicopathological factors need to be re-examined. The results
      of this study should be validated and developed in formal, well-designed
      multicenter clinical trials.

PMID- 29641579
TI  - Lama guanicoe remains from the Chaco ecoregion (Cordoba, Argentina): An
      osteological approach to the characterization of a relict wild population.
AB  - Guanacos (Lama guanicoe) are large ungulates that have been valued by human
      populations in South America since the Late Pleistocene. Even though they were
      very abundant until the end of the 19th century (before the high deforestation
      rate of the last decades), guanacos have nearly disappeared in the Gran Chaco
      ecoregion, with relicts and isolated populations surviving in some areas, such as
      the shrubland area near the saline depressions of Cordoba province, Argentina. In
      this report, we present the first data from a locally endangered guanaco wild
      population, through the study of skeletal remains recovered in La Providencia
      ranch. Our results showed that most of the elements belonged to adults aged
      between 36 and 96 months; sex evaluation showed similar numbers of males and
      females. Statistical analysis of the body size of modern samples from Cordoba
      demonstrated that guanacos from the Chaco had large dimensions and presented
      lower size variability than the modern and archaeological specimens in our
      database. Moreover, they exhibited dimensions similar to those of modern guanacos
      from Patagonia and San Juan, and to archaeological specimens from Ongamira and
      Cerro Colorado, although further genetic studies are needed to corroborate a
      possible phylogenetic relationship. Finally, we used archaeozoological techniques
      to provide a first characterization of a relict guanaco population from the Chaco
      ecoregion, demonstrating its value to the study of modern skeletal remains and
      species conservation biology.

PMID- 29641580
TI  - Clinicopathological analysis of polyploid diffuse large B-cell lymphoma.
AB  - Polyploid chromosomes are those with more than two sets of homologous
      chromosomes. Polyploid chromosomal abnormalities are observed in various
      malignant tumors. The prognosis in such cases is generally poor. However, there
      are no studies examining the prognosis of diffuse large B-cell lymphoma (DLBCL)
      with polyploid chromosomal abnormalities. Therefore, we statistically compared
      the clinicopathological features between polyploid DLBCL and DLBCL without
      polyploid abnormalities. Herein, 51 polyploid DLBCL and 53 control (without
      polyploid chromosomal abnormalities) cases were examined. G-banding method was
      employed to define polyploidy by cytogenetic analysis. Subsequently, flow
      cytometric immunophenotyping and immunohistochemical staining were performed.
      Polyploid DLBCL was defined as DLBCL with either near-tetraploid or greater
      number of chromosomes, as detected by the G-band. In a survival analysis, a
      significantly worse overall survival (OS) was observed for polyploid DLBCL (p =
      0.04; p = 0.02 in cases who received R-CHOP regimens). In a multivariate analysis
      of OS, polyploid chromosomal abnormalities were an independent prognostic factor.
      Our results suggest that polyploid chromosomal abnormalities detected through G
      band may represent a new poor prognostic factor for DLBCL.

PMID- 29641581
TI  - Risk of hip fractures in patients with depressive disorders: A nationwide,
      population-based, retrospective, cohort study.
AB  - BACKGROUND: Some studies have suggested that depressive disorders may play a
      vital role in the incidence of hip fractures. However, nationwide data are
      lacking regarding the association between depressive disorders and hip fractures.
      OBJECTIVE: We aimed to explore the association between depressive disorders and
      new-onset hip fractures. METHODS: We conducted a retrospective study of 11,207
      patients with depressive disorders and 11,207 control patients using Taiwan's
      National Health Insurance Research Database. A Cox regression model was used to
      evaluate the risk of hip fractures in patients with depressive disorders.
      RESULTS: The incidence rate ratio of hip fractures between patients with
      depressive disorders and controls was 1.6 (95% confidence interval [CI] = 1.29
      1.99, P < .001). After adjustment for potential confounders in multivariate
      analysis using the Cox regression model, patients with depressive disorders were
      found to have 1.34 times higher risk of hip fractures than controls (95% CI =
      1.08-1.66, P = .008). Furthermore, age (hazard ratio [HR] = 7.43, 95% CI = 4.94
      11.19, P < .001), hypertension (HR = 1.63, 95% CI = 1.17-2.28, P = .004),
      diabetes mellitus (HR = 1.47, 95% CI = 1.08-1.99, P = .014), cerebrovascular
      disease (HR = 1.76, 95% CI = 1.31-2.35, P < .001), living in rural areas (HR =
      1.88, 95% CI = 1.30-2.70, P = .001), and low monthly income (NT$0-NT$19,000: HR =
      4.08, 95% CI = 1.79-9.29, P = .001 and NT$19,100-NT$42,000: HR = 4.09, 95% CI =
      1.76-9.49, P = .001) were independent risk factors for new-onset hip fractures in
      patients with depressive disorders. CONCLUSION: Depressive disorders might
      increase the risk of new-onset hip fractures, particularly in older patients and
      patients with hypertension, diabetes mellitus, cerebrovascular disease, or low
      socioeconomic status.

PMID- 29641582
TI  - Validity of consumer-grade activity monitor to identify manual wheelchair
      propulsion in standardized activities of daily living.
AB  - BACKGROUND: Hypoactive lifestyle contributes to the development of secondary
      complications and lower quality of life in wheelchair users. There is a need for
      objective and user-friendly physical activity monitors for wheelchair-dependent
      individuals in order to increase physical activity through self-monitoring, goal
      setting, and feedback provision. OBJECTIVE: To determine the validity of Activ8
      Activity Monitors to 1) distinguish two classes of activities: independent
      wheelchair propulsion from other non-propulsive wheelchair-related activities 2)
      distinguish five wheelchair-related classes of activities differing by the
      movement intensity level: sitting in a wheelchair (hands may be moving but
      wheelchair remains stationary), maneuvering, and normal, high speed or assisted
      wheelchair propulsion. METHODS: Sixteen able-bodied individuals performed sixteen
      various standardized 60s-activities of daily living. Each participant was
      equipped with a set of two Activ8 Professional Activity Monitors, one at the
      right forearm and one at the right wheel. Task classification by the Active8
      Monitors was validated using video recordings. For the overall agreement,
      sensitivity and positive predictive value, outcomes above 90% are considered
      excellent, between 70 and 90% good, and below 70% unsatisfactory. RESULTS:
      Division in two classes resulted in overall agreement of 82.1%, sensitivity of
      77.7% and positive predictive value of 78.2%. 84.5% of total duration of all
      tasks was classified identically by Activ8 and based on the video material.
      Division in five classes resulted in overall agreement of 56.6%, sensitivity of
      52.8% and positive predictive value of 51.9%. 59.8% of total duration of all
      tasks was classified identically by Activ8 and based on the video material.
      CONCLUSIONS: Activ8 system proved to be suitable for distinguishing between
      active wheelchair propulsion and other non-propulsive wheelchair-related
      activities. The ability of the current system and algorithms to distinguish five
      various wheelchair-related activities is unsatisfactory.

PMID- 29641583
TI  - Towards a computational model of social norms.
AB  - We describe a computational model of social norms based on identifying values
      that a certain culture finds desirable such as dignity, generosity and
      politeness. The model quantifies these values in the form of Culture-Sanctioned
      Social Metrics (CSSMs) and treats social norms as the requirement to maximize
      these metrics from the perspective of the self, peers and public. This model can
      be used to create realistic social simulations, to explain or predict human
      behavior in specific scenarios, or as a component of robots or agents that need
      to interact with humans in specific social-cultural settings. We validate the
      model by using it to represent a complex deception scenario and showing that it
      can yield non-trivial insights such as the explanation of apparently irrational
      human behavior.

PMID- 29641584
TI  - Know your neighbor: The impact of social context on fairness behavior.
AB  - Laboratory experiments offer an opportunity to isolate human behaviors with a
      level of precision that is often difficult to obtain using other (survey-based)
      methods. Yet, experimental tasks are often stripped of any social context,
      implying that inferences may not directly map to real world contexts. We randomly
      allocate 632 individuals (grouped randomly into 316 dyads) from small villages in
      Sierra Leone to four versions of the ultimatum game. In addition to the classic
      ultimatum game, where both the sender and receiver are anonymous, we reveal the
      identity of the sender, the receiver or both. This design allows us to explore
      how fairness behavior is affected by social context in a natural setting where
      players are drawn from populations that are well-acquainted. We find that average
      offers increase when the receiver's identity is revealed, suggesting that
      anonymous ultimatum games underestimate expected fair offers. This study suggest
      that researchers wishing to relate laboratory behavior to contexts in which the
      participants are well-acquainted should consider revealing the identities of the
      players during game play.

PMID- 29641585
TI  - Tetrapods on the EDGE: Overcoming data limitations to identify phylogenetic
      conservation priorities.
AB  - The scale of the ongoing biodiversity crisis requires both effective conservation
      prioritisation and urgent action. As extinction is non-random across the tree of
      life, it is important to prioritise threatened species which represent large
      amounts of evolutionary history. The EDGE metric prioritises species based on
      their Evolutionary Distinctiveness (ED), which measures the relative contribution
      of a species to the total evolutionary history of their taxonomic group, and
      Global Endangerment (GE), or extinction risk. EDGE prioritisations rely on
      adequate phylogenetic and extinction risk data to generate meaningful priorities
      for conservation. However, comprehensive phylogenetic trees of large taxonomic
      groups are extremely rare and, even when available, become quickly out-of-date
      due to the rapid rate of species descriptions and taxonomic revisions. Thus, it
      is important that conservationists can use the available data to incorporate
      evolutionary history into conservation prioritisation. We compared published and
      new methods to estimate missing ED scores for species absent from a phylogenetic
      tree whilst simultaneously correcting the ED scores of their close taxonomic
      relatives. We found that following artificial removal of species from a
      phylogenetic tree, the new method provided the closest estimates of their "true"
      ED score, differing from the true ED score by an average of less than 1%,
      compared to the 31% and 38% difference of the previous methods. The previous
      methods also substantially under- and over-estimated scores as more species were
      artificially removed from a phylogenetic tree. We therefore used the new method
      to estimate ED scores for all tetrapods. From these scores we updated EDGE
      prioritisation rankings for all tetrapod species with IUCN Red List assessments,
      including the first EDGE prioritisation for reptiles. Further, we identified
      criteria to identify robust priority species in an effort to further inform
      conservation action whilst limiting uncertainty and anticipating future
      phylogenetic advances.

PMID- 29641586
TI  - Application of alignment-free bioinformatics methods to identify an oomycete
      protein with structural and functional similarity to the bacterial AvrE effector
      protein.
AB  - Diverse plant pathogens export effector proteins to reprogram host cells. One of
      the most challenging goals in the molecular plant-microbe field is to
      functionally characterize the complex repertoires of effectors secreted by these
      pathogens. For bacterial pathogens, the predominant class of effectors is
      delivered to host cells by Type III secretion. For oomycetes, the predominant
      class of effectors is defined by a signal peptide that mediates secretion from
      the oomycete and a conserved RxLR motif. Downy mildew pathogens and Phytophthora
      species maintain hundreds of candidate RxLR effector genes in their genomes.
      Although no primary sequence similarity is evident between bacterial Type III
      effectors (T3Es) and oomycete RXLR effectors, some bacterial and oomycete
      effectors have convergently evolved to target the same host proteins. Such
      effectors might have evolved domains that are functionally similar but sequence
      unrelated. We reasoned that alignment-free bioinformatics approaches could be
      useful to identify structural similarities between bacterial and oomycete
      effectors. To test this approach, we used partial least squares regression,
      alignment-free bioinformatics methods to identify effector proteins from the
      genome of the oomycete Hyaloperonospora arabidopsidis that are similar to the
      well-studied AvrE1 effector from Pseudomonas syringae. This approach identified
      five RxLR proteins with putative structural similarity to AvrE1. We focused on
      one, HaRxL23, because it is an experimentally validated effector and it is
      conserved between distantly related oomycetes. Several experiments indicate that
      HaRxL23 is functionally similar to AvrE1, including the ability to partially
      rescue an AvrE1 loss-of-function mutant. This study provides an example of how an
      alignment-free bioinformatics approach can identify functionally similar effector
      proteins in the absence of primary sequence similarity. This approach could be
      useful to identify effectors that have convergently evolved regardless of whether
      the shared host target is known.

PMID- 29641587
TI  - Expression of the inactivating deiodinase, Deiodinase 3, in the pre-metamorphic
      tadpole retina.
AB  - Thyroid hormone (TH) orchestrates amphibian metamorphosis. Thus, this
      developmental phase is often used to study TH-dependent responses in specific
      tissues. However, TH signaling appears early in development raising the question
      of the control of TH availability in specific cell types prior to metamorphosis.
      TH availability is under strict temporal and tissue-specific control by
      deiodinases. We examined the expression of the TH-inactivating enzyme, deiodinase
      type 3 (D3), during early retinal development. To this end we created a Xenopus
      laevis transgenic line expressing GFP from the Xenopus dio3 promoter region
      (pdio3) and followed pdio3-GFP expression in pre-metamorphic tadpoles. To
      validate retinal GFP expression in the transgenic line as a function of dio3
      promoter activity, we used in situ hybridization to compare endogenous dio3
      expression to reporter-driven GFP activity. Retinal expression of dio3 increased
      during pre-metamorphosis through stages NF41, 45 and 48. Both sets of results
      show dio3 to have cell-specific, dynamic expression in the pre-metamorphic
      retina. At stage NF48, dio3 expression co-localised with markers for
      photoreceptors, rods, Opsin-S cones and bipolar neurons. In contrast, in post
      metamorphic juveniles dio3 expression was reduced and spatially confined to
      certain photoreceptors and amacrine cells. We compared dio3 expression at stages
      NF41 and NF48 with TH-dependent transcriptional responses using another
      transgenic reporter line: THbZIP-GFP and by analyzing the expression of T3
      regulated genes in distinct TH availability contexts. At stage NF48, the majority
      of retinal cells expressing dio3 were negative for T3 signaling. Notably, most
      ganglion cells were virtually both dio3-free and T3-responsive. The results show
      that dio3 can reduce TH availability at the cellular scale. Further, a reduction
      in dio3 expression can trigger fine-tuned T3 action in cell-type specific
      maturation at the right time, as exemplified here in photoreceptor survival in
      the pre-metamorphic retina.

PMID- 29641588
TI  - Scaffold hopping from (5-hydroxymethyl) isophthalates to multisubstituted
      pyrimidines diminishes binding affinity to the C1 domain of protein kinase C.
AB  - Protein kinase C (PKC) isoforms play a pivotal role in the regulation of numerous
      cellular functions, making them extensively studied and highly attractive drug
      targets. Utilizing the crystal structure of the PKCdelta C1B domain, we have
      developed hydrophobic isophthalic acid derivatives that modify PKC functions by
      binding to the C1 domain of the enzyme. In the present study, we aimed to improve
      the drug-like properties of the isophthalic acid derivatives by increasing their
      solubility and enhancing the binding affinity. Here we describe the design and
      synthesis of a series of multisubstituted pyrimidines as analogs of C1 domain
      targeted isophthalates and characterize their binding affinities to the PKCalpha
      isoform. In contrast to our computational predictions, the scaffold hopping from
      phenyl to pyrimidine core diminished the binding affinity. Although the novel
      pyrimidines did not establish improved binding affinity for PKCalpha compared to
      our previous isophthalic acid derivatives, the present results provide useful
      structure-activity relationship data for further development of ligands targeted
      to the C1 domain of PKC.

PMID- 29641591
TI  - Correction: Evaluating the impact of fast-fMRI on dynamic functional connectivity
      in an event-based paradigm.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0190480.].

PMID- 29641589
TI  - Training at maximal power in resisted sprinting: Optimal load determination
      methodology and pilot results in team sport athletes.
AB  - AIMS: In the current study we investigated the effects of resisted sprint
      training on sprinting performance and underlying mechanical parameters (force
      velocity-power profile) based on two different training protocols: (i) loads that
      represented maximum power output (Lopt) and a 50% decrease in maximum unresisted
      sprinting velocity and (ii) lighter loads that represented a 10% decrease in
      maximum unresisted sprinting velocity, as drawn from previous research (L10).
      METHODS: Soccer [n = 15 male] and rugby [n = 21; 9 male and 12 female] club-level
      athletes were individually assessed for horizontal force-velocity and load
      velocity profiles using a battery of resisted sprints, sled or robotic resistance
      respectively. Athletes then performed a 12-session resisted (10 * 20-m; and pre-
      post-profiling) sprint training intervention following the L10 or Lopt protocol.
      RESULTS: Both L10 and Lopt training protocols had minor effects on sprinting
      performance (average of -1.4 to -2.3% split-times respectively), and provided
      trivial, small and unclear changes in mechanical sprinting parameters.
      Unexpectedly, Lopt impacted velocity dominant variables to a greater degree than
      L10 (trivial benefit in maximum velocity; small increase in slope of the force
      velocity relationship), while L10 improved force and power dominant metrics
      (trivial benefit in maximal power; small benefit in maximal effectiveness of
      ground force orientation). CONCLUSIONS: Both resisted-sprint training protocols
      were likely to improve performance after a short training intervention in already
      sprint trained athletes. However, widely varied individualised results indicated
      that adaptations may be dependent on pre-training force-velocity characteristics.

PMID- 29641590
TI  - Structural and functional analysis of Utp24, an endonuclease for processing 18S
      ribosomal RNA.
AB  - The precursor ribosomal RNA is processed by multiple steps of nucleolytic
      cleavage to generate mature rRNAs. Utp24 is a PIN domain endonuclease in the
      early 90S precursor of small ribosomal subunit and is proposed to cleave at sites
      A1 and A2 of pre-rRNA. Here we determine the crystal structure of Utp24 from
      Schizosaccharomyces pombe at 2.1 angstrom resolution. Utp24 structurally
      resembles the ribosome assembly factor Utp23 and both contain a Zn-finger motif.
      Functional analysis in Saccharomyces cerevisiae shows that depletion of Utp24
      disturbs the assembly of 90S and abolishes cleavage at sites A0, A1 and A2. The
      90S assembled with inactivated Utp24 is arrested at a post-A0-cleavage state and
      contains enriched nuclear exosome for degradation of 5' ETS. Despite of high
      sequence conservation, Utp24 from other organisms is unable to form an active 90S
      in S. cerevisiae, suggesting that Utp24 needs to be precisely positioned in 90S.
      Our study provides biochemical and structural insight into the role of Utp24 in
      90S assembly and activity.

PMID- 29641593
TI  - Temporal and spatial changes in ion homeostasis, antioxidant defense and
      accumulation of flavonoids and glycolipid in a halophyte Sesuvium portulacastrum
      (L.) L.
AB  - Salinity is an important environmental constraint limiting plant productivity.
      Understanding adaptive responses of halophytes to high saline environments may
      offer clues to manage and improve salt stress in crop plants. We have studied
      physiological, biochemical and metabolic changes in a perennial, fast growing
      halophyte, Sesuvium portulacastrum under 0 mM (control), 150 mM (low salt, LS)
      and 500 mM (high salt, HS) NaCl treatments. The changes in growth, relative water
      content, cation, osmolyte accumulation, H2O2 and antioxidant enzyme activity
      (SOD, CAT and APX) were observed under different treatment conditions. A positive
      correlation was revealed for sodium ion accumulation with malondialdehyde (r2 =
      0.77), proline (r2 = 0.88) and chlorophyll content (r2 = 0.82) under salt
      treatment while a negative correlation was observed with relative tissue water
      content (r2 = -0.73). The roots and leaves showed contrasting accumulation of
      potassium and sodium ions under LS treatment. Temporal and spatial study of
      sodium and potassium ion content indicated differential accumulation pattern in
      roots and leaves, and, high potassium levels in root. Higher H2O2 content was
      recorded in roots than leaves and the antioxidant enzyme activities also showed
      significant induction under salt treatment conditions. Gene expression profiling
      of sodium transporters, Sodium proton exchanger (NHX3), Vacuolar ATPase (vATPase)
      and Salt overly sensitive1 (SOS1) showed up regulation under salt stress after 6
      24 hr of NaCl treatment. Metabolite changes in the salt stressed leaves showed
      increased accumulation of flavonoids (3,5-dihydroxy-6,4'-dimethoxy-flavone-7-O
      [alpha-L-rhamnopyranosyl-(1->6)-beta-D-glucopyranoside], and3,5-dihydroxy-6,3',4'
      trimethoxy-flavone-7-O-[alpha-L-rhamnopyranosyl-(1->6)-beta-D-glucopyranoside] in
      both LS and HS treatments, while a glycolipid, 1-O-linolenyl-2-O-(palmitoyl)-3-O
      galactopyranosyl glycerol, accumulated more in LS over HS treatments and control.
      The results suggest that differential spatial and temporal cation levels in roots
      and leaves, and accumulation of flavanoid and glycolipid could be responsible for
      salt adaptation of S. portulacastrum.

PMID- 29641592
TI  - Ehrlichia chaffeensis TRP120 nucleomodulin binds DNA with disordered tandem
      repeat domain.
AB  - Ehrlichia chaffeensis, the causative agent of human monocytotropic ehrlichiosis,
      secretes several effector proteins that bind host DNA to modulate host gene
      expression. The tandem repeat protein 120 (TRP120), one of the largest effector
      proteins, has four nearly identical tandem repeat (TR) regions that each consists
      of 80 amino acids. In addition to playing a role in ehrlichial binding and
      internalization, TRP120 translocates to the host nucleus where it is thought to
      function as a transcription factor that modulates gene expression. However,
      sequence analysis of TRP120 does not identify the presence of DNA-binding or
      trans-activation domains typical of classical eukaryotic transcription factors.
      Thus, the mechanism by which TRP120 binds DNA and modulates gene expression
      remains elusive. Herein, we expressed the TR regions of the TRP120 protein, and
      characterized its solution structure and ability to bind DNA. TRP120, expressed
      as either a one or two TR repeat, is a monomer in solution, and is mostly
      disordered as determined by circular dichroism (CD) and nuclear magnetic
      resonance (NMR) spectroscopy. Using NMR spectroscopy, we further show that the 1
      TR construct selectively binds GC-rich DNA. Although low pH was required for
      TRP120 TR-DNA interaction, acidic pH alone does not induce any significant
      structural changes in the TR region. This suggests that TRP120 folds into an
      ordered structure upon forming a protein-DNA complex, and thus folding of TRP120
      TR is coupled with DNA binding.

PMID- 29641595
TI  - Correction: The B cell death function of obinutuzumab-HDEL produced in plant
      (Nicotiana benthamiana L.) is equivalent to obinutuzumab produced in CHO cells.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0191075.].

PMID- 29641594
TI  - Nitrogen starvation induces distinct photosynthetic responses and recovery
      dynamics in diatoms and prasinophytes.
AB  - Nitrogen stress is an important control on the growth of phytoplankton and
      varying responses to this common condition among taxa may affect their relative
      success within phytoplankton communities. We analyzed photosynthetic responses to
      nitrogen (N) stress in two classes of phytoplankton that often dominate their
      respective size ranges, diatoms and prasinophytes, selecting species of distinct
      niches within each class. Changes in photosynthetic structures appeared similar
      within each class during N stress, but photophysiological and growth responses
      were more species- or niche-specific. In the coastal diatom Thalassiosira
      pseudonana and the oceanic diatom T. weissflogii, N starvation induced large
      declines in photosynthetic pigments and Photosystem II (PSII) quantity and
      activity as well as increases in the effective absorption cross-section of PSII
      photochemistry (sigma'PSII). These diatoms also increased photoprotection through
      energy-dependent non-photochemical quenching (NPQ) during N starvation. Resupply
      of N in diatoms caused rapid recovery of growth and relaxation of NPQ, while
      recovery of PSII photochemistry was slower. In contrast, the prasinophytes
      Micromonas sp., an Arctic Ocean species, and Ostreococcus tauri, a temperate
      coastal eutrophile, showed little change in photosynthetic pigments and
      structures and a decline or no change, respectively, in sigma'PSII with N
      starvation. Growth and PSII function recovered quickly in Micromonas sp. after
      resupply of N while O. tauri failed to recover N-replete levels of electron
      transfer from PSII and growth, possibly due to their distinct photoprotective
      strategies. O. tauri induced energy-dependent NPQ for photoprotection that may
      suit its variable and nutrient-rich habitat. Micromonas sp. relies upon both
      energy-dependent NPQ and a sustained, energy-independent NPQ mechanism. A
      strategy in Micromonas sp. that permits photoprotection with little change in
      photosynthetic structures is consistent with its Arctic niche, where low
      temperatures and thus low biosynthetic rates create higher opportunity costs to
      rebuild photosynthetic structures.

PMID- 29641596
TI  - A clear trade-off exists between the theoretical efficiency and acceptability of
      dietary changes that improve nutrient adequacy during early pregnancy in French
      women: Combined data from simulated changes modeling and online assessment
      survey.
AB  - BACKGROUND: During pregnancy, the diet of a mother-to-be should be adapted to
      meet increases in nutrient requirements. We analyzed the theoretical efficiency
      and acceptability of different types of tailored dietary changes for pregnant
      women. METHODS: The nutrient adequacy of the diet was evaluated using the PANDiet
      score, by comparing the nutrient intakes of 344 non-pregnant premenopausal women
      (18-44y) with dietary reference intakes for the first trimester of pregnancy.
      Simulations were performed to evaluate the theoretical efficiency of three types
      of ten successive tailored dietary changes in improving nutrient adequacy, with
      graded difficulty in implementation. The acceptability (declared intention to use
      in the diet) of most efficient dietary changes was evaluated during an online
      randomized study including 115 French pregnant women (22-41y). RESULTS: Modifying
      the amount consumed of foods (type-1) did not modify the food repertoire and
      resulted in the smallest theoretical efficiency (increase in the PANDiet score of
      9.8+/-0.2 points), but changes were the most acceptable (probability of the
      intention to use: 0.30-0.78). Conversely, replacing food items by items from the
      same group or eaten at the same time (type-3) broadened the food repertoire
      (3.6+/-1.3 food subgroups added) and resulted in the greatest theoretical
      efficiency (+23.9+/-0.3) but changes were the least acceptable (0.07-0.23).
      Replacing food items within the same subgroup (type-2) slightly broadened the
      food repertoire (+8.0+/-1.3 foods) and resulted in moderate theoretical
      efficiency (+14.8+/-0.2) and intermediate acceptability (0.11-0.35). CONCLUSION:
      A clear trade-off exists between the theoretical efficiency and acceptability of
      dietary changes, with a graded broadening of the food repertoire.

PMID- 29641597
TI  - Associations of stunting in early childhood with cardiometabolic risk factors in
      adulthood.
AB  - Early life stunting may have long-term effects on body composition, resulting in
      obesity-related comorbidities. We tested the hypothesis that individuals stunted
      in early childhood may be at higher cardiometabolic risk later in adulthood. 1753
      men and 1781 women participating in the 1982 Pelotas (Brazil) birth cohort study
      had measurements of anthropometry, body composition, lipids, glucose, blood
      pressure, and other cardiometabolic traits at age 30 years. Early stunting was
      defined as height-for-age Z-score at age 2 years below -2 against the World
      Health Organization growth standards. Linear regression models were performed
      controlling for sex, maternal race/ethnicity, family income at birth, and
      birthweight. Analyses were stratified by sex when p-interaction<0.05. Stunted
      individuals were shorter (beta = -0.71 s.d.; 95% CI: -0.78 to -0.64), had lower
      BMI (beta = -0.14 s.d.; 95%CI: -0.25 to -0.03), fat mass (beta = -0.28 s.d.;
      95%CI: -0.38 to -0.17), SAFT (beta = -0.16 s.d.; 95%CI: -0.26 to -0.06), systolic
      (beta = -0.12 s.d.; 95%CI: -0.21 to -0.02) and diastolic blood pressure (beta = 
      0.11 s.d.; 95%CI: -0.22 to -0.01), and higher VFT/SAFT ratio (beta = 0.15 s.d.;
      95%CI: 0.06 to 0.24), in comparison with non-stunted individuals. In addition,
      early stunting was associated with lower fat free mass in both men (beta = -0.39
      s.d.; 95%CI: -0.47 to -0.31) and women (beta = -0.37 s.d.; 95%CI: -0.46 to -0.29)
      after adjustment for potential confounders. Our results suggest that early
      stunting has implications on attained height, body composition and blood
      pressure. The apparent tendency of stunted individuals to accumulate less fat
      free mass and subcutaneous fat might predispose them towards increased metabolic
      risks in later life.

PMID- 29641598
TI  - Fasudil improves endothelial dysfunction in rats exposed to chronic intermittent
      hypoxia through RhoA/ROCK/NFATc3 pathway.
AB  - Endothelial dysfunction is one of the main pathological changes in Obstructive
      sleep apnoea (OSA). The Rho kinase (ROCK) pathway is associated with endothelial
      dysfunction. However, the interaction between ROCK and nuclear factor of
      activated T cells isoform c3 (NFATc3) in the development of this pathological
      response under chronic intermittent hypoxia (CIH) is unclear. To simulate the OSA
      model, we established a moderate CIH rat model by administering the fraction of
      inspired O2 (FiO2) from 21% to 9%, 20 times/h, 8 h/day for 3 weeks. Fasudil (ROCK
      inhibitor, 8 mg/kg/d, i.p.) was administrated in the rats exposed to CIH for 3
      weeks. Our results demonstrated that CIH caused significantly endothelial
      dysfunction, accompanying with increased ET-1 level, decreased eNOS expression
      and NO production, which reduced ACh-induced vascular relaxation responses.
      Moreover, RhoA/ROCK-2/NFATc3 expressions were up-regulated. Fasudil significantly
      improved CIH induced endothelial dysfunction. Data suggested that the ROCK
      activation is necessary for endothelial dysfunction during CIH.

PMID- 29641599
TI  - Quantifying sleep architecture dynamics and individual differences using big data
      and Bayesian networks.
AB  - The pattern of sleep stages across a night (sleep architecture) is influenced by
      biological, behavioral, and clinical variables. However, traditional measures of
      sleep architecture such as stage proportions, fail to capture sleep dynamics.
      Here we quantify the impact of individual differences on the dynamics of sleep
      architecture and determine which factors or set of factors best predict the next
      sleep stage from current stage information. We investigated the influence of age,
      sex, body mass index, time of day, and sleep time on static (e.g. minutes in
      stage, sleep efficiency) and dynamic measures of sleep architecture (e.g.
      transition probabilities and stage duration distributions) using a large dataset
      of 3202 nights from a non-clinical population. Multi-level regressions show that
      sex effects duration of all Non-Rapid Eye Movement (NREM) stages, and age has a
      curvilinear relationship for Wake After Sleep Onset (WASO) and slow wave sleep
      (SWS) minutes. Bayesian network modeling reveals sleep architecture depends on
      time of day, total sleep time, age and sex, but not BMI. Older adults, and
      particularly males, have shorter bouts (more fragmentation) of Stage 2, SWS, and
      they transition less frequently to these stages. Additionally, we showed that the
      next sleep stage and its duration can be optimally predicted by the prior 2
      stages and age. Our results demonstrate the potential benefit of big data and
      Bayesian network approaches in quantifying static and dynamic architecture of
      normal sleep.

PMID- 29641600
TI  - Memory deficiency, cerebral amyloid angiopathy, and amyloid-beta plaques in
      APP+PS1 double transgenic rat model of Alzheimer's disease.
AB  - Transgenic rat models of Alzheimer's disease were used to examine differences in
      memory and brain histology. Double transgenic female rats (APP+PS1) over
      expressing human amyloid precursor protein (APP) and presenilin 1 (PS1) and
      single transgenic rats (APP21) over-expressing human APP were compared with wild
      type Fischer rats (WT). The Barnes maze assessed learning and memory and showed
      that both APP21 and APP+PS1 rats made significantly more errors than the WT rats
      during the acquisition phase, signifying slower learning. Additionally, the
      APP+PS1 rats made significantly more errors following a retention interval,
      indicating impaired memory compared to both the APP21 and WT rats.
      Immunohistochemistry using an antibody against amyloid-beta (Abeta) showed
      extensive and mostly diffuse Abeta plaques in the hippocampus and dense plaques
      that contained tau in the cortex of the brains of the APP+PS1 rats. Furthermore,
      the APP+PS1 rats also showed vascular changes, including cerebral amyloid
      angiopathy with extensive Abeta deposits in cortical and leptomeningeal blood
      vessel walls and venous collagenosis. In addition to the Abeta accumulation
      observed in arterial, venous, and capillary walls, APP+PS1 rats also displayed
      enlarged blood vessels and perivascular space. Overall, the brain histopathology
      and behavioral assessment showed that the APP+PS1 rats demonstrated behavioral
      characteristics and vascular changes similar to those commonly observed in
      patients with Alzheimer's disease.

PMID- 29641601
TI  - Differential diagnosis between benign and malignant pleural effusion with dual
      energy spectral CT.
AB  - PURPOSE: To investigate the value of spectral CT in the differential diagnosis of
      benign from malignant pleural effusion. METHOD AND MATERIALS: 14 patients with
      benign pleural effusion and 15 patients with malignant pleural effusion underwent
      non-contrast spectral CT imaging. These patients were later verified by the
      combination of disease history, clinical signs and other information with the
      consensus of surgeons and radiologists. Various Spectral CT image parameters
      measured for the effusion were as follows: CT numbers of the polychromatic 140kVp
      images, monochromatic images at 40keV and 100keV, the material density contents
      from the water, fat and blood-based material decomposition images, the effective
      atomic number and the spectral curve slope. These values were statistically
      compared with t test and logistic regression analysis between benign and
      malignant pleural effusion. RESULTS: The CT value of benign and malignant pleural
      effusion in the polychromatic 140kVp images showed no differences (12.61+/-3.39HU
      vs. 14.71+/-5.03HU) (P>0.05), however, they were statistically different on the
      monochromatic images at 40keV (43.15+/-3.79 vs. 39.42+/-2.60, p = 0.005) and
      100keV (9.11+/-1.38 vs. 6.52+/-2.04, p<0.001). There was difference in the
      effective atomic number value between the benign (7.87+/-0.08) and malignant
      pleural effusion (7.90+/-0.02) (P = 0.02). Using 6.32HU as the threshold for CT
      value measurement at 100keV, one could obtain sensitivity of 100% and specificity
      of 66.7% with area-under-curve of 0.843 for differentiating benign from malignant
      effusion. In addition, age and disease history were potential confounding factors
      for differentiating malignant pleural effusion from benign, since the older age
      (61.13+/-12.51 year-old vs48.57+/-12.33 year-old) as well as longer disease
      history (70.00+/-49.28 day vs.28.36+/-21.64 day) were more easily to be found in
      the malignant pleural effusion group than those in the benign pleural effusion
      group. By combining above five factors, one could obtain sensitivity of 100% and
      specificity of 71.4% with area-under-curve of 0.933 for differentiating benign
      from malignant effusion. CONCLUSION: The CT value measurement at both high and
      low energy levels and the effective atomic number obtained in a single spectral
      CT scan can assist the differential diagnosis of benign from malignant pleural
      effusion.Combining them with patient age and disease history can further improve
      diagnostic performance. CLINICAL RELEVANCE/APPLICATION: Clinical findings and
      Spectral CT imaging can provide significant evidences about the nature of pleural
      effusion.

PMID- 29641602
TI  - Effector gene birth in plant parasitic nematodes: Neofunctionalization of a
      housekeeping glutathione synthetase gene.
AB  - Plant pathogens and parasites are a major threat to global food security. Plant
      parasitism has arisen four times independently within the phylum Nematoda,
      resulting in at least one parasite of every major food crop in the world. Some
      species within the most economically important order (Tylenchida) secrete
      proteins termed effectors into their host during infection to re-programme host
      development and immunity. The precise detail of how nematodes evolve new
      effectors is not clear. Here we reconstruct the evolutionary history of a novel
      effector gene family. We show that during the evolution of plant parasitism in
      the Tylenchida, the housekeeping glutathione synthetase (GS) gene was extensively
      replicated. New GS paralogues acquired multiple dorsal gland promoter elements,
      altered spatial expression to the secretory dorsal gland, altered temporal
      expression to primarily parasitic stages, and gained a signal peptide for
      secretion. The gene products are delivered into the host plant cell during
      infection, giving rise to "GS-like effectors". Remarkably, by solving the
      structure of GS-like effectors we show that during this process they have also
      diversified in biochemical activity, and likely represent the founding members of
      a novel class of GS-like enzyme. Our results demonstrate the re-purposing of an
      endogenous housekeeping gene to form a family of effectors with modified
      functions. We anticipate that our discovery will be a blueprint to understand the
      evolution of other plant-parasitic nematode effectors, and the foundation to
      uncover a novel enzymatic function.

PMID- 29641603
TI  - Cell viability assessed in a reproducible model of human osteoblasts derived from
      human adipose-derived stem cells.
AB  - Human adipose tissue-derived stem cells (hASCs) have been subjected to extensive
      investigation because of their self-renewal properties and potential to restore
      damaged tissues. In the literature, there are several protocols for
      differentiating hASCs into osteoblasts, but there is no report on the control of
      cell viability during this process. In this study, we used osteoblasts derived
      from hASCs of patients undergoing abdominoplasty. The cells were observed at the
      beginning and end of bone matrix formation, and the expression of proteins
      involved in this process, including alkaline phosphatase and osteocalcin, was
      assessed. RANKL, Osterix, Runx2, Collagen3A1, Osteopontin and BSP expression
      levels were analyzed using real-time PCR, in addition to a quantitative
      assessment of protein levels of the markers CD45, CD105, STRO-1, and Nanog, using
      immunofluorescence. Rhodamine (Rho123), cytochrome-c, caspase-3, P-27, cyclin D1,
      and autophagy cell markers were analyzed by flow cytometry to demonstrate
      potential cellular activity and the absence of apoptotic and tumor cell processes
      before and after cell differentiation. The formation of bone matrix, along with
      calcium nodules, was observed after 16 days of osteoinduction. The gene
      expression levels of RANKL, Osterix, Runx2, Collagen3A1, Osteopontin, BSP and
      alkaline phosphatase activity were also elevated after 16 days of osteoinduction,
      whereas the level of osteocalcin was higher after 21 days of osteoinduction. Our
      data also showed that the cells had a high mitochondrial membrane potential and a
      low expression of apoptotic and tumor markers, both before and after
      differentiation. Cells were viable after the different phases of differentiation.
      This proposed methodology, using markers to evaluate cell viability, is therefore
      successful in assessing different phases of stem cell isolation and
      differentiation.

PMID- 29641604
TI  - Association of parental obesity with cardiometabolic risk factors in their
      children: The CASPIAN-V study.
AB  - BACKGROUND: The family environment has a crucial role in the development of
      childhood obesity and related cardiometabolic disorders. This study aims to
      investigate the association of parental obesity and cardiometabolic risk factors
      in their children. METHODS: This multicentric cross-sectional study was performed
      on 14400 students (aged 7-18 years) and one of their parents. Students were
      recruited by multistage, stratified cluster sampling from urban and rural areas
      of 30 provinces of Iran. Fasting venous blood was obtained from a random sample
      of 4200 students. Demographic, anthropometric and clinical variables were
      collected. RESULTS: Data of 14002 students and results of blood samples of 3483
      of them were complete and included in the current study. The prevalence of
      obesity in children, fathers, and mothers was 11.4%, 10.6%, and 24.2%,
      respectively. In students, the most commonly observed metabolic abnormality was
      low HDL-C (29.5%); the prevalence of metabolic syndrome and dyslipidemia was 5%
      and 55.7%, respectively. Significant correlations were observed between the body
      mass index (BMI) and waist circumference of parents and weight, height, BMI, and
      waist circumference, as well as systolic and diastolic blood pressure (BP) of
      their children (P< 0.05). In the multivariate model, the risk of excess weight
      (OR: 1.30, 95%CI: 1.17-1.44), obesity (OR: 1.36, 95%CI: 1.18-1.59), abdominal
      obesity (OR: 1.16, 95%CI: 1.05-1.29) and elevated BP (OR: 1.17, 95%CI: 1.04-1.31)
      were higher in those students whose parents had excess weight compared with other
      students. Parental obesity did not have significant association with metabolic
      syndrome and dyslipidemia in their children. CONCLUSIONS: Parental history of
      obesity could be used as a practical approach for the early preventive measures
      and identification of children at risk of cardiometabolic complications.

PMID- 29641605
TI  - Inflammatory markers in postoperative delirium (POD) and cognitive dysfunction
      (POCD): A meta-analysis of observational studies.
AB  - BACKGROUND: The aim of this study was to summarize and discuss the similarities
      and differences in inflammatory biomarkers in postoperative delirium (POD) and
      cognitive dysfunction (POCD). METHODS: A systematic retrieval of literature up to
      June 2017 in PubMed, Embase, the Cochrane Library, the China National Knowledge
      Infrastructure database, and the Wanfang database was conducted. Extracted data
      were analyzed with STATA (version 14). The standardized mean difference (SMD) and
      the 95% confidence interval (95% CI) of each indicator were calculated using a
      random effect model. We also performed tests of heterogeneity, sensitivity
      analysis, assessments of bias, and meta-regression in this meta-analysis.
      RESULTS: A total of 54 observational studies were included. By meta-analysis we
      found significantly increased C-reactive protein (CRP) (9 studies, SMD 0.883, 95%
      CI 0.130 to 1.637, P = 0.022 in POD; 10 studies, SMD -0.133, 95% CI -0.512 to
      0.246, P = 0.429 in POCD) and interleukin (IL)-6 (7 studies, SMD 0.386, 95% CI
      0.054 to 0.717, P = 0.022 in POD; 16 studies, SMD 0.089, 95% CI -0.133 to 0.311,
      P = 0.433 in POCD) concentrations in both POD and POCD patients. We also found
      that the SMDs of CRP and IL-6 from POCD patients were positively correlated with
      surgery type in the meta-regression (CRP: Coefficient = 1.555365, P = 0.001, 10
      studies; IL-6: Coefficient = -0.6455521, P = 0.086, 16 studies). CONCLUSION:
      Available evidence from medium-to-high quality observational studies suggests
      that POD and POCD are indeed correlated with the concentration of peripheral and
      cerebrospinal fluid (CSF) inflammatory markers. Some of these markers, such as
      CRP and IL-6, play roles in both POD and POCD, while others are specific to
      either one of them.

PMID- 29641606
TI  - A novel immunotherapy of Brucellosis in cows monitored non invasively through a
      specific biomarker.
AB  - Brucellosis is an important zoonotic disease causing huge economic losses
      worldwide. Currently no effective immunotherapy for Brucellosis or any biomarker
      to monitor the efficacy of therapy is available. Treatment is ineffective and
      animals remain carrier lifelong. S19 and RB51 are live attenuated vaccine strains
      of Brucella abortus. However, S19 induces only antibody, ineffective for
      intracellular pathogen. RB51 induces cell mediated immunity (CMI) but it is
      Rifampicin resistant. Both organisms are secreted in milk and can infect humans
      and cause abortions in animals. Phage lysed bacteria (lysates) retain maximum
      immunogenicity as opposed to killing by heat or chemicals. We report here the
      successful immunotherapy of bovine Brucellosis by phage lysates of RB51 (RL) and
      S19 (SL). The SL induced strong antibody response and RL stimulated CMI. In vitro
      restimulation of leukocytes from RL immunized cattle induced interferon gamma
      production. A single subcutaneous dose of 2 ml of cocktail lysate (both RL and
      SL), eliminated live virulent Brucella from Brucellosis affected cattle with
      plasma level of Brucella specific 223 bp amplicon undetectable by RT-PCR and
      blood negative for live Brucella by culture in 3 months post-immunization. This
      is the first report on minimally invasive monitoring of the efficacy of
      antibacterial therapy employing plasma RNA specific for live bacteria as a
      biomarker as well as on the use of RB51 phage lysate for successful immunotherapy
      of Brucellosis in cattle.

PMID- 29641607
TI  - Music@Home: A novel instrument to assess the home musical environment in the
      early years.
AB  - The majority of children under the age of 5 appear to show spontaneous enjoyment
      of singing, being exposed to music and interacting with musical instruments, but
      whether variations in engaging in such activities in the home could contribute to
      developmental outcomes is still largely unknown. Critically, researchers lack a
      comprehensive instrument with good psychometric properties to assess the home
      musical environment from infancy to the preschool years. To address this gap,
      this paper presents two studies that describe the development and validation of
      the Music@Home questionnaire, which comprises two versions: Infant and Preschool.
      In Study 1, an initial pool of items was generated and administered to a wide
      audience of parents (n = 287 for the Infant, n = 347 for the Preschool version).
      Exploratory factor analysis was used to identify different dimensions comprising
      the home musical environment of both infants and pre-schoolers, and to reduce the
      initial pool of items to a smaller number of meaningful items. In Study 2,
      convergent and divergent validity and internal and test-retest reliability of the
      new instrument were established, using data from a different sample of
      participants (n = 213 for the Infant, n = 213 for the Preschool version). The
      second study also investigated associations between the Music@Home and musical
      characteristics of the parents, such as their musical education and personal
      engagement with music. Overall, the Music@Home constitutes a novel, valid and
      reliable instrument that allows for the systematic assessment of distinct aspects
      of the home musical environment in families with children under the age of 5.
      Furthermore, the Infant and Preschool versions of the Music@Home present
      differential associations with musical characteristics of the parents opening a
      new area of inquiry into how musical exposure and interaction in the home may
      vary across different developmental stages.

PMID- 29641608
TI  - Probiotic characteristics and zearalenone-removal ability of a Bacillus
      licheniformis strain.
AB  - Zearalenone (ZEN) is a mycotoxin produced by Fusarium species, which is one of
      the main animal feed contaminants causing reproductive disorders in livestock.
      The aim of this study was to evaluate the probiotic characteristics and ZEN
      removal ability of a Bacillus licheniformis strain CK1. The probiotic properties,
      including acidic tolerance, bile salt tolerance, adherence capability, and anti
      pathogenic activities of CK1 were evaluated. CK1 survived after incubation at pH
      2.0 or 3.0 for 3 h, grew well in LB broth containing 0.3% oxgall, possessed
      adherence capability to Caco-2 cells, and inhibited the growth of Escherichia
      coli O157:H7 and Listeria monocytogenes. The ZEN removal ability of CK1 was
      compared with a mineral mycotoxin-adsorbing agent, hydrated sodium calcium
      aluminosilicate (HSCAS), and a well-characterized biological mycotoxin-adsorbing
      agent, Lactobacillus rhamnosus GG (LGG). At 37 degrees C in phosphate-buffered
      saline (PBS, pH 7.0) containing 5 MUg mL-1 of ZEN, the ZEN removal percentage of
      CK1 was 73.0%, which was significantly higher than that of HSCAS and LGG (45.9%
      and 48.4%, respectively). In the pH range of 2.5-8.0, CK1 removed up to 65% of
      ZEN. At temperatures between 4 and 42 degrees C, CK1 removed more than 75% of
      ZEN. In the adsorption stability analysis, the amounts of ZEN removed by CK1 was
      over 30% even after five consecutive rounds of washing procedures. These findings
      demonstrated that CK1 displayed probiotic characteristics and removed ZEN
      effectively. Therefore, CK1 has a great potential for the development of feed
      additive to remove ZEN.

PMID- 29641609
TI  - Rain drives foraging decisions of an urban exploiter.
AB  - Foraging decisions tend to drive individuals toward maximising energetic gains
      within a patchy environment. This study aims to determine the extent to which
      rainfall, and associated changes in food availability, can explain foraging
      decisions within a patchy urbanised landscape, using the Australian white ibis as
      a model species. Ibis density, food consumption rates and food abundance (both
      natural and anthropogenic) were recorded during dry and wet weather within urban
      parks in Sydney, Australia. Rainfall influenced ibis density in these urban
      parks. Of the four parks assessed, the site with the highest level of
      anthropogenic food and the lowest abundance of natural food (earthworms),
      irrespective of weather, was observed to have three times the density of ibis.
      Rainfall significantly increased the rate of earthworm consumption as well as
      their relative availability in all sites. Overall, these density and consumption
      measures indicate that anthropogenic derived foods, mainly from direct feeding by
      people, explain the apparent distribution of ibis across urban parks. However,
      there was evidence of prey-switching when the availability of natural foods
      increased following rainfall, perhaps reflecting selection of particular
      nutrients.

PMID- 29641610
TI  - A distribution-oriented approach to support landscape connectivity for
      ecologically distinct bird species.
AB  - Managing landscape connectivity is a widely recognized overarching strategy for
      conserving biodiversity in human-impacted landscapes. However, planning the
      conservation and management of landscape connectivity of multiple and
      ecologically distinct species is still challenging. Here we provide a spatially
      explicit framework which identifies and prioritizes connectivity conservation and
      restoration actions for species with distinct habitat affinities. Specifically,
      our study system comprised three groups of common bird species, forest
      specialists, farmland-specialists, and generalists, populating a highly
      heterogeneous agricultural countryside in the southwestern Iberian Peninsula. We
      first performed a comprehensive analysis of the environmental variables
      underlying the distributional patterns of each bird species to reveal
      generalities in their guild-specific responses to landscape structure. Then, we
      identified sites which could be considered pivotal in maintaining current levels
      of landscape connectivity for the three bird guilds simultaneously, as well as
      the number and location of sites that need to be restored to maximize
      connectivity levels. Interestingly, we found that a small number of sites defined
      the shortest connectivity paths for the three bird guilds simultaneously, and
      were therefore considered key for conservation. Moreover, an even smaller number
      of sites were identified as critical to expand the landscape connectivity at
      maximum for the regional bird assemblage as a whole. Our spatially-explicit
      framework can provide valuable decision-making support to conservation
      practitioners aiming to identify key connectivity and restoration sites, a
      particularly urgent task in rapidly changing landscapes such as agroecosystems.

PMID- 29641611
TI  - Comparing the cost effectiveness of nature-based and coastal adaptation: A case
      study from the Gulf Coast of the United States.
AB  - Coastal risks are increasing from both development and climate change. Interest
      is growing in the protective role that coastal nature-based measures (or green
      infrastructure), such as reefs and wetlands, can play in adapting to these risks.
      However, a lack of quantitative information on their relative costs and benefits
      is one principal factor limiting their use more broadly. Here, we apply a
      quantitative risk assessment framework to assess coastal flood risk (from climate
      change and economic exposure growth) across the United States Gulf of Mexico
      coast to compare the cost effectiveness of different adaptation measures. These
      include nature-based (e.g. oyster reef restoration), structural or grey (e.g.,
      seawalls) and policy measures (e.g. home elevation). We first find that coastal
      development will be a critical driver of risk, particularly for major disasters,
      but climate change will cause more recurrent losses through changes in storms and
      relative sea level rise. By 2030, flooding will cost $134-176.6 billion (for
      different economic growth scenarios), but as the effects of climate change, land
      subsidence and concentration of assets in the coastal zone increase, annualized
      risk will more than double by 2050 with respect to 2030. However, from the
      portfolio we studied, the set of cost-effective adaptation measures (with benefit
      to cost ratios above 1) could prevent up to $57-101 billion in losses, which
      represents 42.8-57.2% of the total risk. Nature-based adaptation options could
      avert more than $50 billion of these costs, and do so cost effectively with
      average benefit to cost ratios above 3.5. Wetland and oyster reef restoration are
      found to be particularly cost-effective. This study demonstrates that the cost
      effectiveness of nature-based, grey and policy measures can be compared
      quantitatively with one another, and that the cost effectiveness of adaptation
      becomes more attractive as climate change and coastal development intensifies in
      the future. It also shows that investments in nature-based adaptation could meet
      multiple objectives for environmental restoration, adaptation and flood risk
      reduction.

PMID- 29641612
TI  - Informal social accountability in maternal health service delivery: A study in
      Northern Malawi.
AB  - Despite the expansion of literature on social accountability in low-and middle
      income countries, little is known about how health providers experience daily
      social pressure and citizen feedback. This study used a narrative inquiry
      approach to explore the function of daily social accountability relations among
      maternal health care workers in rural Malawi. Through semi-structured interviews
      with 32 nurses and 19 clinicians, we collected 155 feedback cases allowing the
      identification of four main strategies social actors use to express their opinion
      and concerns about maternal health services. We found that women who used
      delivery care express their appreciation for successful deliveries directly to
      the health worker but complaints, such as on absenteeism and poor interpersonal
      behaviour, follow an indirect route via intermediaries such as the health
      workers' spouse, co-workers or the health committee who forward some cases of
      misbehaviour to district authorities. The findings suggest that citizen feedback
      is important for the socialization, motivation and retention of maternal
      healthcare workers in under resourced rural settings. Practitioners and external
      development programmes should understand and recognize the value of already
      existing accountability mechanisms and foster social accountability approaches
      that allow communities as well as health workers to challenge the systemic
      obstacles to quality and respectful service delivery.

PMID- 29641613
TI  - Detection of human vital signs in hazardous environments by means of video
      magnification.
AB  - In cases of natural disasters, epidemics or even in dangerous situations like an
      act of terrorism, battle fields, a shooting or a mountain accident, finding
      survivors is a challenge. In these kind of situations it is sometimes critical to
      know if a person has vital signs or not, without the need to be in contact with
      the victim, thus avoiding jeopardizing the lives of the rescue workers. In this
      work, we propose the use of video magnification techniques to detect small
      movements in human bodies due to breathing that are invisible to the naked eye.
      Two different video magnification techniques, intensity-based and phase-based,
      were tested. The utility of these techniques to detect people who are alive but
      injured in risk situations was verified by simulating a scene with three people
      involved in an accident. Several factors such as camera stability, distance to
      the object, light conditions, magnification factor or computing time were
      analyzed. The results obtained were quite positive for both techniques, intensity
      based method proving more adequate if the interest is in almost instant results
      whereas the phase-based method is more appropriate if processing time is not so
      relevant but the degree of magnification without excessive image noise.

PMID- 29641615
TI  - A new drilling method-Earthworm-like vibration drilling.
AB  - The load transfer difficulty caused by borehole wall friction severely limits the
      penetration rate and extended-reach limit of complex structural wells. A new
      friction reduction technology termed "earthworm-like drilling" is proposed in
      this paper to improve the load transfer of complex structural wells. A
      mathematical model based on a "soft-string" model is developed and solved. The
      results show that earthworm-like drilling is more effective than single-point
      vibration drilling. The amplitude and frequency of the pulse pressure and the
      installation position of the shakers have a substantial impact on friction
      reduction and load transfer. An optimization model based on the projection
      gradient method is developed and used to optimize the position of three shakers
      in a horizontal well. The results verify the feasibility and advantages of
      earthworm-like drilling, and establish a solid theoretical foundation for its
      application in oil field drilling.

PMID- 29641614
TI  - Measuring serum melatonin in postmenopausal women: Implications for epidemiologic
      studies and breast cancer studies.
AB  - BACKGROUND: Circulating melatonin is a good candidate biomarker for studies of
      circadian rhythms and circadian disruption. However, epidemiologic studies on
      circulating melatonin are limited because melatonin is secreted at night, yet
      most epidemiologic studies collect blood during the day when melatonin levels are
      very low, and assays are lacking that are ultrasensitive to detect low levels of
      melatonin reliably. OBJECTIVE: To assess the performance of a refined
      radioimmunoassay in measuring morning melatonin among women. METHODS: We used
      morning serum samples from 47 postmenopausal women ages 48-80 years without a
      history of breast cancer who participated in the San Francisco Bay Area Breast
      Cancer Study, including 19 women who had duplicate measurements. The coefficient
      of variation (CV) and intraclass coefficient (ICC) were estimated using the
      random effect model. RESULTS: Reproducibility for the assay was satisfactory,
      with a CV of 11.2% and an ICC of 98.9%; correlation between the replicate samples
      was also high (R = 0.96). In the 47 women, serum melatonin levels ranged from 0.6
      to 62.6 pg/ml, with a median of 7.0 pg/ml. CONCLUSION: Our results suggest that
      it is possible to reliably measure melatonin in postmenopausal women in morning
      serum samples in large epidemiologic studies to evaluate the role of melatonin in
      cancer etiology or prognosis.

PMID- 29641616
TI  - Correction: Indirect adaptive soft computing based wavelet-embedded control
      paradigms for WT/PV/SOFC in a grid/charging station connected hybrid power
      system.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0183750.].

PMID- 29641617
TI  - Evaluation of preventable adverse drug reactions by implementation of the
      nationwide network of prospective drug utilization review program in Korea.
AB  - BACKGROUND: A prospective Drug Utilization Review (DUR) program has been
      implemented in Korea to improve the quality and safety of medication use.
      OBJECTIVE: To evaluate the influence of the DUR program in reducing incidence of
      preventable adverse drug reactions (pADRs). METHODS: This study was performed
      using administrative data from the Health Insurance Review and Assessment Service
      (HIRA). The claims data for all adult patients with adverse drug events (ADE)
      related diagnoses from 2009 to 2014 were obtained. Incidence rates of first-time
      and repeat pADRs prior to and after DUR program implementation were evaluated.
      Quarterly trends in incidence rates of overall ADE, allergic reactions, and ADRs
      were analyzed. RESULTS: Data extraction covering the period from 2009 to 2014 led
      to the identification of 3,927,662 records. First-time pADR rates decreased
      gradually after implementation of the DUR program (change in slope: -0.016, p =
      0.02). The program had a similar influence on repeat pADR rates (change in slope:
      -0.006, p<=0.01). The program did not decrease rates of first-time or repeat
      allergic reactions (change in slope: 0.018, p = 0.07 and 0.003, p = 0.04,
      respectively). In the cohort aged <=65 years, first-time pADR rate reduction was
      significant (28.2% [27.1-29.3] in <=18 years, and 19.8% [18.1-21.5] in 19-64
      years). In contrast, first-time pADR rate was increased by 0.6% [-0.7-1.9] in
      patients >=65 years. CONCLUSION: Implementation of the prospective DUR program
      effectively reduced the number of pADRs. In the future, to reduce non-preventable
      ADRs such as allergic reactions, provision of clinical information including
      allergy history should be added to the DUR program.

PMID- 29641618
TI  - A moral house divided: How idealized family models impact political cognition.
AB  - People's political attitudes tend to fall into two groups: progressive and
      conservative. Moral Politics Theory asserts that this ideological divide is the
      product of two contrasting moral worldviews, which are conceptually anchored in
      individuals' cognitive models about ideal parenting and family life. These
      models, here labeled the strict and nurturant models, serve as conceptual
      templates for how society should function, and dictate whether one will endorse
      more conservative or progressive positions. According to Moral Politics Theory,
      individuals map their parenting ideals onto the societal domain by engaging the
      nation-as-family metaphor, which facilitates reasoning about the abstract social
      world (the nation) in terms of more concrete world experience (family life). In
      the present research, we conduct an empirical examination of these core
      assertions of Moral Politics Theory. In Studies 1-3, we experimentally test
      whether family ideals directly map onto political attitudes while ruling out
      alternative explanations. In Studies 4-5, we use both correlational and
      experimental methods to examine the nation-as-family metaphor's role in
      facilitating the translation of family beliefs into societal beliefs and,
      ultimately, political attitudes. Overall, we found consistent support for Moral
      Politics Theory's assertions that family ideals directly impact political
      judgment, and that the nation-as-family metaphor serves a mediating role in this
      phenomenon.

PMID- 29641619
TI  - Medicalising normality? Using a simulated dataset to assess the performance of
      different diagnostic criteria of HIV-associated cognitive impairment.
AB  - OBJECTIVE: The reported prevalence of cognitive impairment remains similar to
      that reported in the pre-antiretroviral therapy era. This may be partially
      artefactual due to the methods used to diagnose impairment. In this study, we
      evaluated the diagnostic performance of the HIV-associated neurocognitive
      disorder (Frascati criteria) and global deficit score (GDS) methods in comparison
      to a new, multivariate method of diagnosis. METHODS: Using a simulated
      'normative' dataset informed by real-world cognitive data from the observational
      Pharmacokinetic and Clinical Observations in PeoPle Over fiftY (POPPY) cohort
      study, we evaluated the apparent prevalence of cognitive impairment using the
      Frascati and GDS definitions, as well as a novel multivariate method based on the
      Mahalanobis distance. We then quantified the diagnostic properties (including
      positive and negative predictive values and accuracy) of each method, using
      bootstrapping with 10,000 replicates, with a separate 'test' dataset to which a
      pre-defined proportion of 'impaired' individuals had been added. RESULTS: The
      simulated normative dataset demonstrated that up to ~26% of a normative control
      population would be diagnosed with cognitive impairment with the Frascati
      criteria and ~20% with the GDS. In contrast, the multivariate Mahalanobis
      distance method identified impairment in ~5%. Using the test dataset, diagnostic
      accuracy [95% confidence intervals] and positive predictive value (PPV) was best
      for the multivariate method vs. Frascati and GDS (accuracy: 92.8% [90.3-95.2%]
      vs. 76.1% [72.1-80.0%] and 80.6% [76.6-84.5%] respectively; PPV: 61.2% [48.3
      72.2%] vs. 29.4% [22.2-36.8%] and 33.9% [25.6-42.3%] respectively). Increasing
      the a priori false positive rate for the multivariate Mahalanobis distance method
      from 5% to 15% resulted in an increase in sensitivity from 77.4% (64.5-89.4%) to
      92.2% (83.3-100%) at a cost of specificity from 94.5% (92.8-95.2%) to 85.0% (81.2
      88.5%). CONCLUSION: Our simulations suggest that the commonly used diagnostic
      criteria of HIV-associated cognitive impairment label a significant proportion of
      a normative reference population as cognitively impaired, which will likely lead
      to a substantial over-estimate of the true proportion in a study population, due
      to their lower than expected specificity. These findings have important
      implications for clinical research regarding cognitive health in people living
      with HIV. More accurate methods of diagnosis should be implemented, with
      multivariate techniques offering a promising solution.

PMID- 29641621
TI  - Increasing the Vertical Dimension of Occlusion: A Multicenter Retrospective
      Clinical Comparative Study on 100 Patients with Fixed Tooth-Supported, Mixed, and
      Implant-Supported Full-Arch Rehabilitations.
AB  - This multicenter retrospective clinical study was aimed at comparing the effects
      of an increase in vertical dimension of occlusion (VDO) in patients with fixed
      rehabilitations. Expert clinicians retrospectively evaluated 100 patients treated
      with an increase of the VDO and fixed dental prostheses (FDPs) supported by
      teeth, implants, or both. The patients were divided into three study groups
      according to the type of support of restorations in posterior areas, as follows:
      partially edentulous patients with posterior teeth-supported rehabilitations and
      no implants in posterior segments (group A), partially edentulous patients with
      posterior mixed rehabilitations and at least one osseointegrated implant in
      posterior segments (group B), and completely edentulous patients with posterior
      implant-supported rehabilitations (group C). The new VDO was tested with mock
      ups, temporary restorations, or removable appliances. The patients were followed
      up for at least 1 year after the delivery of final restorations. Clinical
      variables were collected retrospectively, such as presence of referred self
      reported bruxism and temporomandibular joint or muscle symptoms before treatment,
      extension of the dental arches, increase in VDO, restorative materials, and
      functional complications. Descriptive statistics were analyzed; the three
      experimental groups were compared with one-way analysis of variance (ANOVA)
      followed by Tukey post hoc test for the quantitative variables and with logistic
      regression using the likelihood ratio test for the qualitative variables.
      Statistically significant differences were reported among the experimental groups
      for functional complications. Functional and prosthetic complications after the
      VDO increase were not frequent. Functional complications were mainly noticed in
      group C but usually were no longer evident after 2 weeks. No significant
      differences were found between groups in terms of prosthetic complications and
      self-reported bruxism.

PMID- 29641620
TI  - Development and characterization of an immunochromatographic test for the rapid
      diagnosis of Talaromyces (Penicillium) marneffei.
AB  - Talaromyces (Penicillium) marneffei is a thermally dimorphic fungus that can
      cause opportunistic systemic mycoses in patients infected with the human
      immunodeficiency virus (HIV). It has also been reported among patients with other
      causes of immunodeficiency, such as systemic lupus erythematosus, cancer, organ
      transplanted patients receiving immunosuppressive drug and adult onset
      immunodeficiency syndromes. Recent studies indicate that the clinical
      manifestations, laboratory findings and treatment strategies of talaromycosis
      (penicilliosis) marneffei are different between patients with and without HIV
      infection. Therefore early and accurate diagnosis of talaromycosis marneffei is
      crucial to the proper management and treatment. Since current diagnostic methods
      are currently inadequate, the aim of this study was to develop an
      immunochromatographic test (ICT) for the detection of T. marneffei yeast antigens
      in urine samples. The highly T. marneffei-specific monoclonal antibody 4D1 (MAb
      4D1) conjugated with gold colloid at pH 6.5 was used as signal generator. The
      nitrocellulose membrane was lined with T. marneffei cytoplasmic yeast antigen (TM
      CYA) to serve as the test line, and rabbit anti-mouse IgG was the control line.
      Subjecting the assembled test strip to urine samples containing T. marneffei
      antigen produced a visible result within 20 minutes. The sensitivity limit of the
      assay was 3.125MUg/ml of TM CYA. The ICT was used to test urine samples from 66
      patients with blood culture confirmed talaromycosis marneffei, 42 patients with
      other fungal or bacterial infections, and 70 normal healthy individuals from
      endemic area of T. marneffei. The test exhibited sensitivity, specificity and
      accuracy of 87.87%, 100% and 95.5%, respectively. This rapid, user-friendly test
      holds great promise for the serodiagnosis of T. marneffei infection.

PMID- 29641622
TI  - Clinical Outcome After 8 to 10 Years of Immediately Restored Single Implants
      Placed in Extraction Sockets and Healed Ridges.
AB  - Recent systematic reviews point to the scarcity of single implants followed up
      longer than 5 years, and the incidence of biologic/technical complications is
      underreported. This prospective follow-up study documents 8- to 10-year clinical
      outcomes of immediately restored single implants in extraction sockets (immediate
      implant treatment [IIT]) and healed bone (conventional implant treatment [CIT]).
      Patients received a single, chemically modified, moderately rough titanium
      implant and a provisional crown on the day of surgery in the anterior maxilla
      (second premolar to second premolar). Provisional crowns were replaced by
      permanent crowns after 10 weeks. Implant survival, complications, crestal bone
      changes, plaque score, probing depth, and bleeding on probing were regularly
      recorded up to 10 years of follow-up. Of 16 patients who underwent IIT, 11 could
      be evaluated after 8 years. Of the 23 patients who received an implant in healed
      bone, 18 were finally evaluated. One implant failed in the IIT group at 12 weeks;
      all implants survived in the CIT group; 38% of the patients experienced at least
      one complication; 10% had one or more biologic complications, whereas 31%
      experienced one or more technical complications. There were no significant
      changes in crestal bone level from 1 to >= 8 years of follow-up for either group
      or between IIT and CIT at any time point (P >= .129). Only 6.9% (2 of 29)
      implants demonstrated progressive bone loss > 2 mm combined with pockets >= 6 mm.
      Immediately restored single implants in extraction sockets and healed ridges
      demonstrate good long-term outcomes in terms of implant survival, crestal bone
      loss, and peri-implant health. However, biologic and especially technical
      complications are common.

PMID- 29641623
TI  - Outcomes After 25 Years of Periodontal Treatment and Maintenance of a Patient
      Affected by Generalized Severe Aggressive Periodontitis.
AB  - This report describes the long-term outcomes of nonsurgical periodontal therapy
      and supportive periodontal treatment (SPT) of a 21-year-old patient affected by
      generalized aggressive periodontitis at multiple teeth with a compromised
      prognosis. After 25 years of SPT, no teeth had been extracted and no periodontal
      pockets associated with bleeding on probing were present. Radiographic analysis
      showed an improvement in infrabony defects, demonstrating long-term improvement
      is possible with nonsurgical periodontal treatment provided that smoking is not
      present and the patient is included in a strict SPT.

PMID- 29641624
TI  - Allogeneic Bone Block Volume Preservation in Ridge Augmentation for Implants.
AB  - Allogeneic bone blocks are commonly used for bone augmentation in implant
      dentistry. Allogeneic bone blocks have the advantage of containing growth factors
      and the original human scaffold. A major disadvantage is the risk of substantial
      graft volume decrease due to resorption. The purpose of this study was to
      evaluate whether corticocancellous allogeneic bone blocks can predictably
      maintain graft volume to allow implant placement and esthetic restoration. A
      total of 141 allogeneic bone blocks were placed in 117 patients, allowing for 183
      implants. The implant success rate was 96.7% after 6 to 96 months of follow-up.

PMID- 29641626
TI  - Clinical and CBCT Evaluation of Combined Periodontal Regenerative Therapies Using
      Enamel Matrix Derivative and Deproteinized Bovine Bone Mineral With or Without
      Collagen Membrane.
AB  - Use of collagen membrane (CM) with deproteinized bovine bone mineral (DBBM) and
      enamel matrix derivative (EMD) in periodontal regenerative therapy was evaluated.
      A total of 40 intrabony defects in periodontitis patients were treated. Clinical
      parameters and filled bone volume (FBV) and rate (FBR) were assessed. Probing
      pocket depth (PPD) was reduced significantly at 12 months with CM treatment,
      while clinical attachment level (CAL), FBV, and FBR showed similar improvements.
      In stratified analyses, CM-treated thick-biotype patients showed significant
      improvement in PPD and CAL. Regenerative therapy with the use of EMD and DBBM
      showed similar improvements in periodontal tissue regeneration with or without
      CM. The combination with CM appeared to influence the healing of soft tissue and
      was effective in decreasing pocket depth.

PMID- 29641625
TI  - The Conometric Concept: A 5-Year Follow-up of Fixed Partial Monolithic Zirconia
      Restorations Supported by Cone-in-Cone Abutments.
AB  - The use of the cone-in-cone connection to support definitive restorations was
      previously evaluated in cases involving full-acrylic resin or hybrid acrylic
      resin composite prostheses. The aim of this study was to evaluate the performance
      of definitive fixed partial prostheses made with monolithic zirconia and
      supported by cone-in-cone abutments and integrated implants. Implants were placed
      into healed sites and fresh extraction sockets. The prostheses were placed in the
      posterior regions of partially edentulous patients after healing periods of 3
      months. A total of 76 patients received fixed monolithic zirconia restorations
      splinted with cone-in-cone connections to two implants that were followed up
      yearly for 5 years. At each follow-up visit, peri-implant bone levels and pocket
      depths were recorded. Esthetic, functional, and biologic United States Public
      Health Services parameters modified by the World Dental Federation study design
      were assessed at the last follow-up appointments. The opposing dentition was
      categorized by type of restoration and supporting structure at the time of
      placement of the definitive zirconia partial restoration and at the 5-year follow
      up. The treatment achieved an 88.2% success rate and a 97.4% survival rate at the
      5-year follow-up. None of the prostheses became loose or detached. One fixed
      prosthesis (0.76%) fractured 41 months after placement. No significant difference
      involving peri-implant bone and probing levels between the experimental times was
      found. The results of this research indicated that abutment-prosthesis cone-in
      cone connections were successful within the 5-year study period.

PMID- 29641627
TI  - Morphometric Variation in Maxillary Central Incisors and Its Influence on
      Gingival Characteristics: A Preliminary Epidemiologic Study in an Indian
      Population.
AB  - The presence of interdental papilla between the maxillary central incisors has a
      considerable influence on harmonizing esthetics and biologic functions.
      Preliminary investigations indicate an association between tooth shapes and
      periodontal characteristics. This study aimed to evaluate the prevalence of
      morphologic variation in maxillary central incisors and its influence on gingival
      characteristics. It was determined that varied crown forms have a definite
      influence on gingival characteristics, which could act as a valuable guideline in
      periodontal, restorative, and anterior implant placement procedures.

PMID- 29641628
TI  - Marginal Fit of All-Ceramic Crowns Before and After Cementation: An In Vitro
      Study.
AB  - The marginal integrity of all-ceramic crowns for anterior and posterior teeth
      were evaluated. A total of 60 ceramic crowns (In-Ceram Alumina, IPS e.max Press,
      and Lava) were fabricated for the epoxy resin maxillary first central incisor and
      first molar and divided into three groups (n = 20). The crowns were measured at
      the facial, lingual, mesial, and distal finish lines (52 points) before and after
      cementation using scanning electron microscopy. The results were analyzed using
      one-way analysis of variance, paired samples t test, and independent t test. The
      mean values of marginal gaps were within acceptable clinical limits before and
      after cementation. The values of the anterior crowns at the buccal finish line
      were higher than those at the proximal finish line areas (P < .05). However,
      these were insignificant at four measurement areas for posterior crowns (P >
      .05). Marginal gaps of crowns at the anterior teeth were higher than at the
      posterior teeth for all groups.

PMID- 29641629
TI  - Color Compatibility of Gingival Shade Guides and Gingiva-Colored Dental Materials
      with Healthy Human Gingiva.
AB  - The CIELab and CIEDE2000 coverage error (DeltaE*COV and DeltaE'COV, respectively)
      of basic shades of different gingival shade guides and gingiva-colored
      restorative dental materials (n = 5) was calculated as compared to a previously
      compiled database on healthy human gingiva. Data were analyzed using analysis of
      variance with Tukey-Kramer multiple-comparison test (P < .05). A 50:50%
      acceptability threshold of 4.6 for DeltaE* and 4.1 for DeltaE' was used to
      interpret the results. DeltaE*COV / DeltaE'COV ranged from 4.4/3.5 to 8.6/6.9.
      The majority of gingival shade guides and gingiva-colored restorative materials
      exhibited statistically significant coverage errors above the 50:50%
      acceptability threshold and uneven shade distribution.

PMID- 29641630
TI  - Laser De-epithelialization of Autogenous Gingival Graft for Root Coverage and
      Soft Tissue Augmentation Procedures.
AB  - The purpose of this case report was to introduce a novel technique for de
      epithelializing autogenous gingival graft that can be combined with coronally
      advanced flap for root coverage and soft tissue augmentation. This technique
      allows for easier, predictable harvesting of connective tissue of excellent
      quality and quantity without inclusion of undesirable submucosa or adipose
      tissues. Reduced surgical chair time and double protection of the donor site
      using the combination of cyanoacrylate and periodontal dressing allowed for
      uneventful postoperative healing.

PMID- 29641631
TI  - The Effect of Primary Stabilization of the Graft in a Combined Surgical and
      Prosthodontic Ridge Preservation Protocol: A Prospective Controlled Clinical
      Pilot Study.
AB  - The objective of this study was to evaluate the influence of a modified surgical
      and prosthodontic ridge preservation protocol with direct insertion of a
      temporary but fixed reconstruction at the time of extraction. After atraumatic
      extraction and filling of the socket with an in situ-hardening graft material to
      fortify the outline position of the marginal rim of the former socket, the change
      in buccal volume was documented with an analog impression and digital scanning
      and processing workflow of the data. Changes in the soft tissue profile were
      calculated as the difference between the digitized surface on the day of
      extraction and at the 6-month follow-up. The results indicate that in the group
      with stabilization of the graft material with a fixed temporary appliance, the
      amount of buccal volume loss was reduced to -1.06 mm (95% confidence interval = 
      1.8 to -0.29) in comparison to the group without temporary reconstruction for
      sites in the mandible (-2.09 mm), and for the group in the maxilla without
      temporary reconstruction (-2.17 mm). The difference was statistically significant
      (P = .0059). Using a single-stage approach while simultaneously reconstructing
      the esthetic appearance of the patient with a fixed temporary appliance, the
      described modification of current ridge preservation techniques is able to reduce
      buccal volume loss after extraction. This might aid the final esthetic
      rehabilitation of a visible site after extraction by means of a conventional or
      implant-based fixed reconstruction.

PMID- 29641632
TI  - Vertical 3D Bone Reconstruction with Simultaneous Implantation: A Case Series
      Report.
AB  - Tooth loss generally leads to a corresponding loss of supporting bone structures,
      jeopardizing correct implant placement. Bone augmentation procedures facilitate
      reconstruction of the alveolar contours but lengthen treatment time by about 4 to
      9 months. The aim of this case series report is to describe the short-term
      results of the combination of three-dimensional bone augmentation using the shell
      technique in conjunction with simultaneous implantation. A total of 10 patients
      who underwent autologous bone augmentation using the shell technique with
      simultaneous implantation were retrospectively examined. The shell technique is
      an augmentation procedure using thin cortical bone plates adapted to the buccal
      and oral walls of the defect to rebuild the contours of the alveolar ridge. The
      remaining spaces are filled with bone chips. Healing time before second stage
      surgery was 4 months. The vertical bone defect at the beginning (VD), the height
      of the vertical bone graft, resorption at the time of second-stage surgery (BR1)
      and 1 year after prosthetic rehabilitation (BR2), the total resorption between
      augmentation and 1 year (BRtot), and the vertical bone loss of the implant (VBL)
      were measured. VD was 3.1 mm. Values for BR1 and BR2 were 0.4 and 0.45 mm,
      respectively, resulting in a total bone loss of 0.85 mm of bone loss (BRtot). VBL
      was 0.45 mm 1 year after prosthetic rehabilitation. The simultaneous approach of
      vertical bone augmentation in the shell technique and implantation shows
      excellent results in bone reconstruction and stability up to 1 year after
      prosthetic reconstruction and can shorten treatment time by 4 to 9 months.

PMID- 29641633
TI  - Three-Dimensional Bone Augmentation and Immediate Implant Placement via
      Transcrestal Sinus Lift: 8-Year Clinical Outcomes.
AB  - When the edentulous posterior maxilla shows severe atrophy (Cawood and Howell
      Class V to VI), the traditional approach requires at least two surgical
      procedures. The first is a sinus lift (alone or with guided bone regeneration),
      and the second is to position implants. This article illustrates a technique that
      allows three-dimensional reconstruction of the sinus, placing an allogenous fresh
      bone block and simultaneous implant positioning using a computer-guided implant
      surgery.

PMID- 29641634
TI  - Microchemical and Micromorphologic ESEM-EDX Analysis of Bone Mineralization at
      the Thread Interface in Human Dental Implants Retrieved for Mechanical
      Complications After 2 Months to 17 Years.
AB  - The aim of this study was to analyze the degree of mineralization around nine
      clinically stable titanium dental implants retrieved after 2 months to 17 years
      for mechanical complications from five patients. The micromorphology and
      microchemistry of the interface bone at the coronal and apical sides of the
      threads were analyzed by environmental scanning electron microscope and energy
      dispersive X-ray spectroscopy (EDX) on histologic samples. Mineralization was
      investigated by atomic calcium-to-nitrogen (Ca/N), phosphorous-to-nitrogen (P/N),
      and calcium-to-phosphorous (Ca/P) ratio evaluation (statistical analysis by two
      way analysis of variance with Student-Newman-Keuls; P < .05). EDX showed higher
      Ca/N, P/N, and Ca/P values for the bone at the coronal side compared to the
      apical side of the threads in the long-term (>= 14 years) samples. The two most
      significant findings were that (1) the interface bone located at the coronal side
      of the implant threads was generally more mineralized than the interface bone
      located at the apical side, and (2) the mineralization of the peri-implant bone
      at the interface increased over time. A higher degree of mineralization was found
      at 2 months in an immediately loaded implant when compared to the 2-month
      submerged unloaded control, likely related to the different remodeling events
      (coronal vs apical side of the implant threads) due to the direction of the
      loading forces.

PMID- 29641635
TI  - Extended Maxillary Sinus Augmentation to the Apical Area of the Neighboring
      Teeth: Advantages and Limitations.
AB  - The extension of sinus floor augmentation beyond the edentulous area, apical to
      the adjacent teeth, has many therapeutic advantages, but the reliability and
      safety of the procedure has not been assessed in depth. The present study
      compares the gain of bone anterior and posterior to the edentulous area and
      evaluates potential advantages and limitations in the clinical setting. The
      maximum vertical bone height in the edentulous and extended maxillary sinus
      augmentation (EMSA) areas and the thickness of the sinus membrane of 65 patients
      were measured. Those measurements were analyzed using the t test and Pearson
      correlations. The average vertical bone gain was 11.98 +/- 3.53 mm in the
      edentulous sinus area and 8.60 +/- 3.89 mm in the EMSA area (P < .05). Minor
      perforations of the sinus membrane occurred in 4 patients. There were no
      postsurgical graft contaminations or periradicular changes during follow-up. EMSA
      is a reliable and safe procedure with a very low complication rate. This approach
      is effective and safe for patients who have lost part of their posterior
      dentition. It enables future implant placement while avoiding the need for sinus
      reentry and proximal teeth extraction.

PMID- 29641636
TI  - Rapid assessment of the orchid bee fauna (Hymenoptera: Apidae: Euglossini) in the
      vicinity of an urban Atlantic Forest remnant in Sao Paulo, Brazil.

PMID- 29641637
TI  - Edaphic fauna in a vegetation gradient in the Sete Cidades National Park.
AB  - The vegetation physionomy and cover can show patterns of diversity and
      composition of the edaphic community, depending on the quantity and quality of
      litter in a specific habitat. The objective of this study was to evaluate the
      effect of the vegetation gradient formed by Graminoid Field (GRF), Cerrado Sensu
      Stricto (CSS), Cerradao (CRD) and Semideciduous Seasonal Forest (SSF) on density,
      diversity and composition of the edaphic fauna community in two seasons of the
      year, in the Sete Cidades National Park (Piaui state). For fauna sampling, a
      total of eight pitfall traps, distanced 10 m, were placed in each area in the
      central part of each system, where they remained for seven days. In the wet
      period, there was a tendency to increase the number of individuals as a function
      of the complexity of the vegetation formation, with the inverse occurring in the
      dry period. It was verified an environmental variation of the climatic factors
      temperature and humidity according to the vegetal formation, contributing to a
      heterogeneous distribution of the fauna. The GRF formation presented a
      significantly lower value of average richness only in the dry period. Regarding
      the variables of diversity and uniformity, they did not show drastic variations
      in relation to the vegetation gradient studied. The dominant groups in the
      vegetation gradient were Formicidae, Coleoptera, Aranae, Acari and Collembola,
      with reduction of the number of Coleoptera in the dry season. Principal component
      analysis (PCA) revealed greater differences in the composition of the communities
      between the vegetation formations for the rainy season. At this time, the
      formations SSF and CRD were associated to a greater diversity of invertebrates
      than CSS and GRF, demonstrating the influence of the vegetation complexity on the
      soil fauna community.

PMID- 29641638
TI  - Development and reprotuction of Spodoptera eridania on natural hosts and
      artificial diet.
AB  - The development and reproductive potential of Spodoptera eridania (Stoll, 1782)
      (Lepidoptera, Noctuidae) was compared on natural and artificial diets. Its
      biology was determined under laboratory conditions, providing an artificial diet,
      leaves of white clover and the peach cultivar 'Chimarrita' and fruits and leaves
      of the apple cultivar 'Gala'. Larvae of S. eridania could not complete their
      biological cycle when fed on apple fruits or peach leaves. The artificial diet
      provided the shortest development time, with a cycle of 28.5+/-0.14 days from egg
      to adult and 37.3% total viability. Apple leaves led to a longer development time
      from egg to adult (62.8+/-1.22 days) and lower total viability (23%) and white
      clover provided the highest total viability (54.3%). The results showed that S.
      eridania can use white clover and apple leaves to develop normally in apple
      orchards. The reduction of food sources such as white clover used by the larvae
      results in infestation and damage to fruits from "test bites".

PMID- 29641640
TI  - Horizontal Bone Reconstruction on sites with different amounts of native bone: a
      retrospective study.
AB  - The lack of guidelines for bone augmentation procedures might compromise decision
      making in implantology. The objective of this study was to perform a
      retrospective study to verify the outcomes of horizontal bone reconstruction in
      implant dentistry with different types of materials and amounts of native bone in
      the recipient bed to allow for a new guideline for horizontal bone
      reconstruction. One hundred preoperative CT scans were retrospectively evaluated
      and categorized in accordance to horizontal bone defects as presence (Group P) or
      absence (Group A) of cancellous bone in the recipient bed. Different approaches
      were used to treat the edentulous ridge and the outcomes were defined either as
      satisfactory or unsatisfactory regarding the possibility of implant placement.
      The percentage distribution of the patients according to the presence or absence
      of cancellous bone was 92% for Group P and 8% for Group A. In Group P, 98% of the
      patients had satisfactory outcomes, and the use of autografts had 100% of
      satisfactory outcomes in this group. In Group A, 37.5% of the patients had
      satisfactory outcomes, and the use of autografts also yielded 100% of
      satisfactory outcomes. The use of allografts and xenografts in Group A had 0% and
      33.3% of satisfactory outcomes, respectively. Therefore, it seems reasonable to
      speculate that the presence of cancellous bone might be predictive and
      predictable when the decision includes bone substitutes. In cases of absence of
      cancellous bone in the recipient bed, the use of a vitalized graft seems to be
      mandatory.

PMID- 29641641
TI  - Risk factors and comorbidities in Brazilian patients with orofacial clefts.
AB  - Considering that environmental risk factors substantially contribute to the
      etiology of orofacial clefts and that knowledge about the characteristics and
      comorbidities associated with oral clefts is fundamental to promoting better
      quality of life, this study aimed to describe the risk factors, main
      characteristics, and comorbidities of a group of patients with cleft lip and/or
      cleft palate (CL/P) from Rio Grande do Norte (RN), Brazil. Data were obtained
      from 173 patients with CL/P using a form from the Brazilian database on Orofacial
      Clefts. Most patients were male with cleft lip and palate and had a normal size
      and weight at birth; presented few neonatal intercurrent events; and had anemia
      and respiratory and cardiovascular diseases as main associated comorbidities.
      They also required timely surgical rehabilitation and multidisciplinary care to
      stimulate their neuropsychomotor development. In addition, a high frequency of
      familial recurrence and of parental consanguinity was evidenced in the studied
      population, especially for the cleft lip and cleft palate type. Other relevant
      findings were the considerable maternal exposure to alcohol, infections, smoking,
      and hypertension, as well as low supplementation with vitamins and minerals and
      deliberate consumption of analgesics, antibiotics, and antihypertensives during
      pregnancy. Characterization of the CL/P patient profile is essential for the
      planning of health services and integration among the health professionals
      involved in the diagnosis and treatment of these malformations. Our results
      reinforce the need for additional research to confirm the association between
      environmental factors and the development of orofacial clefts.

PMID- 29641642
TI  - Bond strength between a polymer-infiltrated ceramic network and a composite for
      repair: effect of several ceramic surface treatments.
AB  - The effects of several ceramic surface treatments on bond strength of a polymer
      infiltrated ceramic network and resin composite as repair material were
      evaluated. CAD-CAM blocks of a polymer-infiltrated ceramic network (Vita Enamic)
      were sliced and subjected to aging process, followed by embedding in acrylic
      resin. The bonding/repair area was treated as follows (n = 30): C- without
      treatment; UA- universal adhesive application; FM- 10% hydrofluoric acid and
      silane application; OM-airborne-particle abrasion with aluminum oxide and silane
      application; RP- tribochemical silica coating; and CA- surface grinding and
      application of universal adhesive. Composite resin cylinders were made on the
      treated surface. Specimens from each group were assigned randomly to two
      subgroups (n = 15) considering storage condition: Baseline (shear tests after 48
      hours) or Storage (tests after 6 months under distilled water). The treated
      surfaces were analyzed by goniometry, roughness, and SEM. Two-way ANOVA and 1-way
      ANOVA were applied to analyze the bond data and roughness / contact angle data,
      respectively, followed by Tukey's test (alpha = 5%). Surface treatments and
      storage conditions affected bond strengths (p < 0.01). Surface grinding (CA)
      followed by universal adhesive promoted the highest value of bond strength (14.5
      +/- 4.8 MPa for baseline, 8.5 +/- 3.4 MPa for storage) and the roughest ceramic
      surface. Grinding with silicon carbide paper (simulating diamond bur) followed by
      the application of a universal adhesive system is the best option for repairing
      fractures of the polymer-infiltrated ceramic network.

PMID- 29641639
TI  - The status of cryptococcosis in Latin America.
AB  - Cryptococcosis is a life-threatening fungal infection caused by the encapsulated
      yeasts Cryptococcus neoformans and C. gattii, acquired from the environment. In
      Latin America, as occurring worldwide, C. neoformans causes more than 90% of the
      cases of cryptococcosis, affecting predominantly patients with HIV, while C.
      gattii generally affects otherwise healthy individuals. In this region,
      cryptococcal meningitis is the most common presentation, with amphotericin B and
      fluconazole being the antifungal drugs of choice. Avian droppings are the
      predominant environmental reservoir of C. neoformans, while C. gattii is
      associated with several arboreal species. Importantly, C. gattii has a high
      prevalence in Latin America and has been proposed to be the likely origin of some
      C. gattii populations in North America. Thus, in the recent years, significant
      progress has been made with the study of the basic biology and laboratory
      identification of cryptococcal strains, in understanding their ecology,
      population genetics, host-pathogen interactions, and the clinical epidemiology of
      this important mycosis in Latin America.

PMID- 29641643
TI  - Is the fluoride intake by diet and toothpaste in children living in tropical semi
      arid city safe?
AB  - Data about total fluoride intake in children living in a tropical semi-arid
      climate city is scarce, thus we conducted this study. Fifty-eight children aged
      two to five years, living in a Brazilian tropical city with optimally fluoridated
      water were selected. Dietary samples were collected using the duplicate diet
      method on two non-consecutive days in the children's home toothpaste was
      determined by subtracting the amount of fluoride recovered after brushing from
      the amount placed on the toothbrush. The mean total dose (SD) of fluoride intake
      was 0.043(0.016) mg F.kg-1.d-1, with the major (60.6%) contribution from water.
      The factors associated with the ingestion of fluoride from toothpaste were
      fluoride concentration of the toothpaste (p = 0.03) and the use of kids
      toothpaste (p = 0.02). The findings suggest that children have a low fluoride
      intake, measured by at-home meals and use of fluoride toothpaste; drinking water
      is the main source of fluoride ingestion.

PMID- 29641644
TI  - Reactive oxygen species generation mediated by NADPH oxidase and PI3K/Akt
      pathways contribute to invasion of Streptococcus agalactiae in human endothelial
      cells.
AB  - BACKGROUND Streptococcus agalactiae can causes sepsis, pneumonia, and meningitis
      in neonates, the elderly, and immunocompromised patients. Although the virulence
      properties of S. agalactiae have been partially elucidated, the molecular
      mechanisms related to reactive oxygen species (ROS) generation in infected human
      endothelial cells need further investigation. OBJECTIVES This study aimed to
      evaluate the influence of oxidative stress in human umbilical vein endothelial
      cells (HUVECs) during S. agalactiae infection. METHODS ROS production during S.
      agalactiae-HUVEC infection was detected using the probe CM-H2DCFDA.
      Microfilaments labelled with phalloidin-FITC and p47phox-Alexa 546 conjugated
      were analysed by immunofluorescence. mRNA levels of p47phox (NADPH oxidase
      subunit) were assessed using Real Time qRT-PCR. The adherence and intracellular
      viability of S. agalactiae in HUVECs with or without pre-treatment of DPI,
      apocynin (NADPH oxidase inhibitors), and LY294002 (PI3K inhibitor) were evaluated
      by penicillin/gentamicin exclusion. Phosphorylation of p47phox and Akt activation
      by S. agalactiae were evaluated by immunoblotting analysis. FINDINGS Data showed
      increased ROS production 15 min after HUVEC infection. Real-Time qRT-PCR and
      western blotting performed in HUVEC infected with S. agalactiae detected
      alterations in mRNA levels and activation of p47phox. Pre-treatment of
      endothelial cells with NADPH oxidase (DPI and apocynin) and PI3K/Akt pathway
      (LY294002) inhibitors reduced ROS production, bacterial intracellular viability,
      and generation of actin stress fibres in HUVECs infected with S. agalactiae.
      CONCLUSIONS ROS generation via the NADPH oxidase pathway contributes to invasion
      of S. agalactiae in human endothelial cells accompanied by cytoskeletal
      reorganisation through the PI3K/Akt pathway, which provides novel evidence for
      the involvement of oxidative stress in S. agalactiae pathogenesis.

PMID- 29641645
TI  - Association between Microvolt T-Wave Alternans and Malignant Ventricular
      Arrhythmias in Chagas Disease.
AB  - BACKGROUND: Sudden cardiac death is the most frequent death mechanism in Chagas
      disease, responsible for 55% to 65% of the deaths of patients with chronic Chagas
      cardiomyopathy (CCC). The most often involved electrophysiological mechanisms are
      ventricular tachycardia and ventricular fibrillation. The implantable
      cardioverter defibrillator (ICD) has a beneficial role in preventing sudden death
      due to malignant ventricular arrhythmias, and, thus the correct identification of
      patients at risk is required. The association of microvolt T-wave alternans
      (MTWA) with the appearance of ventricular arrhythmias has been assessed in
      different heart diseases. The role of MTWA is mostly unknown in patients with
      CCC. OBJECTIVES: To evaluate the association between MTWA and the occurrence of
      malignant ventricular arrhythmias in patients with CCC. METHOD: This is a case
      control study including patients with CCC and ICD, with history of malignant
      ventricular arrhythmias (case group), and patients with CCC and no history of
      those arrhythmias (control group). The MTWA test results were classified as
      negative and non-negative (positive and indeterminate). The significance level
      adopted was a = 0.05. RESULTS: We recruited 96 patients, 45 cases (46.8%) and 51
      controls (53.1%). The MTWA test was non-negative in 36/45 cases (80%) and 15/51
      controls (29.4%) [OR = 9.60 (95%CI: 3.41 - 27.93)]. After adjustment for known
      confounding factors in a logistic regression model, the non-negative result
      continued to be associated with malignant ventricular arrhythmias [OR = 5.17
      (95%CI: 1.05 - 25.51)]. CONCLUSION: Patients with CCC and history of malignant
      ventricular arrhythmias more often have a non-negative MTWA test as compared to
      patients with no history of arrhythmia.

PMID- 29641646
TI  - Frequency of Subclinical Atherosclerosis in Brazilian HIV-Infected Patients.
AB  - BACKGROUND: AIDS as well as atherosclerosis are important public health problems.
      The longer survival among HIV-infected is associated with increased number of
      cardiovascular events in this population, and this association is not fully
      understood. OBJECTIVES: To identify the frequency of subclinical atherosclerosis
      in HIV-infected patients compared to control subjects; to analyze associations
      between atherosclerosis and clinical and laboratory variables, cardiovascular
      risk factors, and the Framingham coronary heart disease risk score (FCRS).
      METHODS: Prospective cross-sectional case-control study assessing the presence of
      subclinical atherosclerosis in 264 HIV-infected patients and 279 controls.
      Clinical evaluation included ultrasound examination of the carotid arteries,
      arterial stiffness by pulse wave velocity (PWV) and augmentation index (AIx),
      laboratory analysis of peripheral blood, and cardiovascular risk according to
      FCRS criteria. The significance level adopted in the statistical analysis was p <
      0.05. RESULTS: Plaques were found in 37% of the HIV group and 4% of controls (p <
      0.001). Furthermore, carotid intima-media thickness was higher in the HIV group
      than in controls (p < 0.001). Patients with carotid plaque had higher fasting
      glucose, total cholesterol, low-density lipoprotein cholesterol, and
      triglycerides than those without plaques. The presence of HIV, adjusted for age,
      overweight/obesity, and smoking increased by almost fivefold the risk of
      atherosclerotic carotid plaque (OR: 4.9; 95%CI: 2.5-9.9; p < 0.001). Exposure to
      protease inhibitors did not influence carotid intima-media thickness, was not
      associated with carotid plaque frequency, and did not alter the mechanical
      characteristics of the arterial system (PWV and AIx). CONCLUSIONS: HIV-infected
      patients are at increased risk of atherosclerosis in association with classical
      cardiovascular risk factors. Treatment with protease inhibitors does not promote
      functional changes in the arteries, and shows no association with increased
      frequency of atherosclerotic plaques in carotid arteries. The FCRS may be
      inappropriate for this population.

PMID- 29641647
TI  - Translation and cross-cultural adaptation into Brazilian Portuguese of the Mood
      and Feelings Questionnaire (MFQ) - Long Version.
AB  - Introduction Major depressive disorder (MDD) is prevalent among young people,
      with a high incidence during adolescence. It is, therefore, important to have
      reliable instruments to capture the construct of depression in this population.
      The objective of the present work is to describe the process of translation and
      cultural adaptation of the Mood and Feelings Questionnaire (MFQ) - Long Version,
      into Brazilian Portuguese. Method We followed the International Society for
      Pharmacoeconomics and Outcomes Research (ISPOR) guidelines for translation and
      cultural adaptation, including the steps of preparation, forward translation,
      reconciliation, back-translation, back-translation review, harmonization,
      cognitive debriefing, review of cognitive debriefing results and finalization,
      proofreading and final report. Cognitive debriefing was conducted in a sample of
      adolescent patients and their respective caregivers at mental health clinics
      affiliated with the Brazilian public health system. Results Results suggest that
      the items were well understood and that the MFQ seems to be an appropriate
      instrument for use with Brazilian adolescents and caregivers. Conclusions The
      Brazilian Portuguese MFQ - Long Version constitutes an adequate tool for the
      assessment of depression among adolescents. Future studies are required to
      evaluate psychometric properties of the instrument.

PMID- 29641648
TI  - Early trauma, attachment experiences and comorbidities in schizophrenia.
AB  - OBJECTIVE: To evaluate attachment patterns in subjects with schizophrenia and
      their relationships to early traumatic events, psychotic symptoms and
      comorbidities. METHODS: Twenty patients diagnosed with schizophrenia according to
      criteria from the Diagnostic and Statistical Manual of Mental Disorders, 5th
      edition (DSM-5) underwent retrospective symptom assessment and careful assessment
      of the number and manner of childhood caregiver changes. The Diagnostic Interview
      for Psychosis and Affective Disorders (DI-PAD) was used to assess symptoms
      related to schizophrenia (positive and negative symptoms), depression and mania.
      Anxiety disorder comorbidities were assessed by the Liebowitz Social Anxiety
      Scale (LSAS), Yale-Brown Obsessions and Compulsions Scale (Y-BOCS) and Panic and
      Schizophrenia Interview (PaSI). Experience in Close Relationships - Relationship
      Structures (ECR-RS) and Early Trauma Inventory Self Report-Short Form (ETISR-SF)
      were used to assess attachment patterns and traumatic history, respectively.
      RESULTS: Moderate and significant correlations between attachment patterns and
      early trauma showed that greater severity of anxious attachment was predicted by
      a higher frequency of total early traumas (Spearman rho = 0.446, p = 0.04),
      mainly general traumas (rho = 0.526, p = 0.017; including parental illness and
      separation, as well as natural disaster and serious accidents). Among the
      correlations between early trauma and comorbid symptoms, panic attacks occurring
      before the onset of schizophrenia showed significant and positive correlations
      with ETISR-SF total scores and the sexual trauma subscale. CONCLUSION: Children
      with an unstable early emotional life are more vulnerable to the development of
      psychopathology, such as panic anxiety symptoms. Traumatic events may also
      predict later schizophrenia.

PMID- 29641649
TI  - Borderline personality disorder: an adaptation of the Taiwan short version of the
      screening inventory into Brazilian Portuguese.
AB  - Objective The current study presents the translation and adaptation of the 20
      item Taiwan version of the Borderline Personality Inventory (BPI) into Brazilian
      Portuguese (BPI-P). Methods After translation and back-translation, the Brazilian
      Portuguese version was administered to three samples: patients with borderline
      personality disorder, psychiatric patients with comorbid substance use disorder
      and volunteers with no reported mental disorders. Results Significant differences
      between groups for borderline scores (analysis of variance [ANOVA], F = 52.923, p
      = 0.01) were found but there were no significant correlations between scores for
      borderline personality disorder and alcohol or nicotine dependence. The BPI-P had
      satisfactory validity for borderline personality disorder, even when anxiety and
      depression were present, with an area under the receiver operating characteristic
      curve of 0.931 at a cutoff point of 14. Conclusion This study provides support
      for the potential utility of the BPI-P as a screening instrument for clinical
      practice in Portuguese speaking countries, including outpatients with alcohol and
      nicotine use disorders in early or sustained remission.

PMID- 29641650
TI  - European Portuguese adaptation and validation of dilemmas used to assess moral
      decision-making.
AB  - Objective To adapt and validate a widely used set of moral dilemmas to European
      Portuguese, which can be applied to assess decision-making. Moreover, the
      classical formulation of the dilemmas was compared with a more focused moral
      probe. Finally, a shorter version of the moral scenarios was tested. Methods The
      Portuguese version of the set of moral dilemmas was tested in 53 individuals from
      several regions of Portugal. In a second study, an alternative way of questioning
      on moral dilemmas was tested in 41 participants. Finally, the shorter version of
      the moral dilemmas was tested in 137 individuals. Results Results evidenced no
      significant differences between English and Portuguese versions. Also, asking
      whether actions are "morally acceptable" elicited less utilitarian responses than
      the original question, although without reaching statistical significance.
      Finally, all tested versions of moral dilemmas exhibited the same pattern of
      responses, suggesting that the fundamental elements to the moral decision-making
      were preserved. Conclusions We found evidence of cross-cultural validity for
      moral dilemmas. However, the moral focus might affect utilitarian/deontological
      judgments.

PMID- 29641651
TI  - Association between race/skin color and premature birth: a systematic review with
      meta-analysis.
AB  - OBJECTIVE: To analyze the association between race/skin color and the occurrence
      of prematurity. METHODS: Meta-analysis with observational studies, selected by a
      systematic review in the bibliographic databases Medline and Biblioteca Virtual
      da Saude with the descriptors: "Race or ethnic group" and "ethnicity and health"
      associated with the words "infant premature" and "obstetric labor premature".
      Articles published in the period from 2010 to 2014, of the observational
      epidemiological type, in Portuguese, English and Spanish, were included. Articles
      that did not have abstracts or that were review articles, theses, dissertations,
      and editorials were excluded. We adopted the relative risk and their respective
      confidence intervals (95%CI) as measures of effect, obtained through the random
      effect model and represented by the forest plot type graph. The Egger test and
      the Newcastle-Ottawa scale, respectively, were used to analyze possible
      publication biases and the quality of the studies. RESULTS: Of the 926 articles
      identified, 17 were eligible for the study. Of the 17 full texts published, seven
      were retrospective cohort studies, nine were cross-sectional studies, and one was
      a case-control study. Except for one study, the others reported a positive
      association between race/color of skin and prematurity. Compared with full-term
      newborns, the relative risk of the combined effect in those born preterm was 1.51
      (95%CI 1.39-1.69). The funnel chart suggested publication bias. CONCLUSIONS: The
      present meta-analysis indicated a positive association for the risk of
      prematurity according to race/skin color.

PMID- 29641652
TI  - Estimated cost of asthma in outpatient treatment: a real-world study.
AB  - OBJECTIVE: To estimate the cost of diagnosis and treatment of asthma. METHODS: We
      used the perspective of society. We sequentially included for 12 months, in 2011
      2012, 117 individuals over five years of age who were treated for asthma in the
      Pneumology and Allergy-Immunology Services of the Piquet Carneiro Polyclinic,
      Universidade do Estado do Rio de Janeiro. All of them were interviewed twice with
      a six-month interval for data collection, covering 12 months. The cost units were
      identified and valued according to defined methods. We carried out a sensitivity
      analysis and applied statistical methods with a significance level of 5% for cost
      comparisons between subgroups. RESULTS: The study consisted of 108 patients, and
      73.8% of them were women. Median age was 49.5 years. Rhinitis was present in
      83.3% of the individuals, and more than half were overweight or obese. Mean
      family income was U$915.90/month (SD = 879.12). Most workers and students had
      absenteeism related to asthma. Total annual mean cost was U$1,291.20/patient (SD
      = 1,298.57). The cost related to isolated asthma was U$1,155.43/patient-year (SD
      = 1,305.58). Obese, severe, and uncontrolled asthmatic patients had higher costs
      than non-obese, non-severe, and controlled asthmatics, respectively. Severity and
      control level were independently associated with higher cost (p = 0.001 and
      0.000, respectively). The direct cost accounted for 82.3% of the estimated total
      cost. The cost of medications for asthma accounted for 62.2% of the direct costs
      of asthma. CONCLUSIONS: Asthma medications, environmental control measures, and
      long-term health leaves had the greatest potential impact on total cost
      variation. The results are an estimate of the cost of treating asthma at a
      secondary level in the Brazilian Unified Health System, assuming that the
      treatment used represents the ideal approach to the disease.

PMID- 29641653
TI  - Caries and fluoridated water in two Brazilian municipalities with low prevalence
      of the disease.
AB  - OBJECTIVE: To analyze the association between exposure to fluoridated water and
      dental caries in a context of widespread use of fluoride toothpaste in Brazil, in
      a scenario of low prevalence of the disease. METHODS: This is a cross-sectional
      observational study, of the census type, in the form of a double population-based
      epidemiological survey carried out in two municipalities of the state of Sao
      Paulo in 2014. The sample consisted of adolescents aged 11 and 12 years, exposed
      (n = 184) or not exposed (n = 128) to fluoridated water for at least five years.
      The populations studied lived in communities of the same geographic region and
      had small demographic size and similar socioeconomic classification, differing
      only in the exposure (Silveiras) or not exposure (Sao Jose do Barreiro) to
      fluoridated water. The experience, magnitude, and degree of polarization of
      dental caries in these populations were analyzed using the DMFT and SiC indexes,
      and the association was tested using Pearson's chi-square statistics and
      prevalence ratio between those not exposed and those exposed to fluoridated
      water. RESULTS: Although caries experience (DMFT >= 1) was not associated with
      exposure to fluoridated water (chi-square = 1.78; p = 0.18; alpha = 5%), a
      significant difference was observed in the magnitude with which the disease
      reached the population: the means of DMFT were 1.76 in those exposed and 2.60 in
      those not exposed and the means of SiC were 4.04 and 6.16, respectively. The
      degree of polarization, indicated by the percentage of subjects with DMFT = 0,
      was different, being it higher (41.8%) in subjects exposed and lower (34.3%) in
      subjects not exposed. The prevalence ratio between those not exposed and those
      exposed was 1.13, indicating little expressiveness in prevalence difference.
      CONCLUSIONS: Exposure to fluoridated water implied lower mean values for the DMFT
      and SiC indexes, even in the presence of the concomitant exposure to fluoridated
      toothpaste, in a scenario of low prevalence of the disease, and with a similar
      pattern of caries distribution in the populations analyzed.

PMID- 29641654
TI  - Individual and contextual factors associated to the self-perception of oral
      health in Brazilian adults.
AB  - OBJECTIVE: To analyze how individual characteristics and the social context,
      together, are associated with self-perception of the oral health. METHODS: A
      multilevel cross-sectional study with data from the Brazilian National Health
      Survey 2013, the United Nations Development Program, and the National Registry of
      Health Establishments. The explanatory variables for the "oral health perception"
      outcome were grouped, according to the study framework, into biological
      characteristics (sex, color, age), proximal social determinants (literacy,
      household crowding, and socioeconomic stratification), and distal (years of
      schooling expectancy at age 18, GINI, Human Development Index, and per capita
      income). The described analysis was performed, along with bivariate Poisson
      analysis and multilevel Poisson analysis for the construction of the explanatory
      model of oral health perception. All analyzes considered the sample weights.
      RESULTS: Both the biological characteristics and the proximal and distal social
      determinants were associated with the perception of oral health in the bivariate
      analysis. A higher prevalence of bad oral health was associated to lower years of
      schooling expectancy (PR = 1.31), lower per capita income (PR = 1.45), higher
      income concentration (PR = 1.41), and worse human development (PR = 1.45).
      Inversely, oral health services in both primary and secondary care were
      negatively associated with oral health perception. All the biological and
      individual social characteristics, except reading and writing, made up the final
      explanatory model along with the distal social determinants of the Human
      Development Index and coverage of basic care in the multilevel analysis.
      CONCLUSIONS: Biological factors, individual and contextual social determinants
      were associate synergistically with the population's perception of oral health.
      It is necessary to improve individual living conditions and the implementation of
      public social policies to improve the oral health of the population.

PMID- 29641655
TI  - Effect of dental pain and caries on the quality of life of Brazilian preschool
      children.
AB  - OBJECTIVE: To investigate the impact of dental pain on daily performances among
      five-year-old Brazilian children. METHODS: The study used data of 7,280 five-year
      old children participating in the 2010 Brazilian Oral Health Survey (SBBrasil
      2010 Project). Children were clinically examined and their parents or carers were
      interviewed at their homes. The outcome was the prevalence of the oral impacts on
      daily performance, and the explanatory variable was dental pain in the last six
      months. Other independent variables were children's gender and skin color/race,
      family income, household overcrowding, and caries experience (dmft). Rao-Scott
      test and Poisson regression for complex samples were carried out. RESULTS: The
      prevalence of impacts on daily performances was 26.1% (95%CI 22.3-30.2).
      Significant associations were found between the outcome and pain, caries
      experience, and sociodemographic variables. After adjusting for the independent
      variables, only pain and caries remained significant. Impacts on daily
      performances were more frequent among children with pain (PR = 1.14, 95%CI 1.06
      1.23) compared to those without pain. Children with low dmft (PR = 1.90, 95%CI
      1.39-2.60) and those with high dmft (PR = 3.53, 95%CI 2.78-4.49) had a higher
      prevalence of impact than those with no caries experience. CONCLUSIONS: Dental
      pain and caries had strong negative impacts on the five-year-old children's daily
      performances regardless of their demographic and socioeconomic characteristics.

PMID- 29641656
TI  - Adherence to physical activity in adults with chronic diseases: ELSA-Brasil.
AB  - OBJECTIVE: The objective of this study is to investigate the adherence and the
      factors that influence adherence to physical activity in adults with
      dyslipidemia, hypertension, or diabetes. METHODS: The analyses were based on data
      collected at the baseline of the 14,521 participants from the study ELSA-Brasil
      aged between 35 and 74 years. The level of leisure time physical activity was
      determined using the International Physical Activity Questionnaire. Logistic
      regression analyses were performed to examine the influence of the demographic
      data, socioeconomic conditions, perceived health status, and access to exercise
      facilities in the neighborhood on adherence to physical activity. RESULTS: Men
      with hypertension and dyslipidemia were more active than women. The results show
      that 17.8%, 15.1%, and 13.9% of the subjects who reported dyslipidemia,
      hypertension, and diabetes, respectively, adhere to the physical activity
      recommendations. The factors positively associated with adherence were higher
      education and income. Older individuals who reported poor perceived health, were
      overweight and obese, regularly smoked, and had fewer opportunities to exercise
      in the neighborhood presented lower adherence. CONCLUSIONS: The number of adults
      with dyslipidemia, hypertension, and diabetes who adhere to the physical activity
      recommendations is very low. Higher education and income are positively
      associated with adherence, while age, excess body weight, negative perceived
      health, regular smoking, and lack of opportunity to exercise in the neighborhood
      were considered barriers to physical activity.

PMID- 29641657
TI  - Infant mortality trend in the city of Rio Branco, AC, 1999 to 2015.
AB  - OBJECTIVE: Analyze the trend of infant mortality in Rio Branco, state of Acre,
      from 1999 to 2015. METHODS: An ecological observational study of a time series,
      in which data from deaths from the Information System on Mortality and Births of
      the Information System on Live Births were used. The annual percentage change was
      estimated using the Joinpoint software. RESULTS: The infant mortality rate
      decreased from 26.99 in 1999 to 14.50 in 2015 per 1,000 live births, with an
      annual percentage change of -4.37 (95%CI -5.4- -3.4). When stratified by age
      components, the neonatal period presented an annual percentage change of -4.73
      (95%CI -5.7- -3.7), and the post-neonatal period was -3.7 (95%CI -5.4- -2.0).
      Avoidability, avoidable causes and poorly defined causes showed a downward trend
      throughout the period and causes not clearly preventable showed an upward trend
      until 2008. The group of causes that contributed most to the infant deaths during
      the period studied was perinatal diseases, followed by malformations, infectious
      and parasitic diseases, and respiratory diseases. CONCLUSIONS: Despite the
      decreasing trend in infant mortality rates in the capital compared to developed
      countries, it is relatively high.

PMID- 29641659
TI  - Curative procedures of oral health and structural characteristics of primary
      dental care.
AB  - OBJECTIVE: To evaluate if the provision of clinical dental care, by means of the
      main curative procedures recommended in Primary Health Care, is associated with
      team structural characteristics, considering the presence of a minimum set of
      equipment, instrument, and supplies in Brazil's primary health care services.
      METHODS: A cross-sectional exploratory study based on data collected from 18,114
      primary healthcare services with dental health teams in Brazil, in 2014. The
      outcome was created from the confirmation of five clinical procedures performed
      by the dentist, accounting for the presence of minimum equipment, instrument, and
      supplies to carry them out. Covariables were related to structural
      characteristics. Poisson regression with robust variance was used to obtain crude
      and adjusted prevalence ratios, with 95% confidence intervals. RESULTS: A total
      of 1,190 (6.5%) dental health teams did not present the minimum equipment to
      provide clinical dental care and only 2,498 (14.8%) had all the instrument and
      supplies needed and provided the five curative procedures assessed. There was a
      positive association between the outcome and the composition of dental health
      teams, higher workload, performing analysis of health condition, and monitoring
      of oral health indicators. Additionally, the dental health teams that planned and
      programmed oral health actions with the primary care team monthly provided the
      procedures more frequently. Dentists with better employment status, career plans,
      graduation in public health or those who underwent permanent education activities
      provided the procedures more frequently. CONCLUSIONS: A relevant number of
      Primary Health Care services did not have the infrastructure to provide clinical
      dental care. However, better results were found in dental health teams with oral
      health technicians, with higher workload and that plan their activities, as well
      as in those that employed dentists with better working relationships, who had
      dentists with degrees in public health and who underwent permanent education
      activities.

PMID- 29641658
TI  - Were policies in Brazil effective to reducing trans fat from industrial origin in
      foods?
AB  - OBJECTIVE: To determine the trans fatty acids content of processed foods
      frequently consumed by adults living in a Rio de Janeiro, Brazil, after the
      enactment of a mandatory trans fatty acids labelling policy. METHODS: Between
      February 2014 and January 2015, a specifically dietary questionnaire was
      completed by 107 adults to assess the frequency of processed foods consumption.
      The most commonly consumed products from the survey, including vegetable oils,
      margarine, biscuits, snacks, cheese bread (pao de queijo), french fries,
      cheeseburger and ice cream, were then analyzed for their trans fatty acids
      content using gas chromatography with a flame ionization detector. RESULTS:
      Differences in the levels of trans fatty acids were observed among 22 products
      analyzed, considering that trans fatty acids content ranged between 0.0 g/100 g
      in samples of cream cracker biscuit 1 and olive oil to 0.83 g/100 g in samples of
      cheeseburger (fast food), 0.51 g/100 g in samples of frozen pao de queijo and
      12.92 g/100 g in samples of chocolate sandwich cookies with cream filling 2. The
      overall trans fatty acids content of the different samples of margarine brands
      was 0.20 g/100 g for brand 1 and 0.0 g/100 g for brand 2. These data are
      significantly lower than those observed in a survey conducted in 2003, when the
      regulation had been enacted. CONCLUSIONS: Our data indicate that Brazilian
      regulation is very likely implicated in the observed drop in trans fatty acids of
      the most processed foods but has yet to eliminate them, which reinforces the
      urgent need to revise the legislation, since a minimum amount of trans fat does
      not mean that the food product does not contain this type of fat.

PMID- 29641660
TI  - Hospitalizations for cancer in international migrants versus local population in
      Chile.
AB  - OBJECTIVE: To compare cancer hospital morbidity among the local population and
      the immigrant population in Chile. METHODS: This is a prevalence study based on
      the analysis of hospital discharges of all the health centers of Chile. Cancer
      hospital discharges were characterized in 2012 according to the migratory status.
      The crude and specific rates of hospital morbidity for this cause were estimated
      for the analysis of their association with migratory status using zero-inflated
      negative binomial regression, adjusted for sociodemographic variables. RESULTS:
      The neoplasms were the third cause of hospital discharges for immigrants and the
      seventh one for Chileans. The adjusted rate of cancer hospital discharges was
      higher for Chileans than immigrants, and the latter had fewer days of
      hospitalization and greater proportion of surgical interventions. In the group of
      immigrants, cancer hospital discharges mainly corresponded to patients belonging
      to the private system (46%), and in the group of Chileans they mainly
      corresponded to patients in the public system (71.1%). We observed a large
      difference in the proportion of cancer hospital discharges for patients with no
      health insurance between the two populations (22.6%: immigrants, 1.0%: Chileans).
      In both populations, the three most frequent types of cancer were: (i) lymphoid
      tissue, hematopoietic organs, and related tissues, (ii) digestive organs, and
      (iii) breast cancer. CONCLUSIONS: Models of differentiated care should be
      considered for immigrants, with the creation of specific programs of information,
      coverage, and protection against cancer. More information on this problem must be
      generated at the local and international level.

PMID- 29641662
TI  - Associations among body composition, inflammatory profile and disease extent in
      ulcerative colitis patients.
AB  - OBJECTIVE: The aim of our study was to assess body composition status and its
      association with inflammatory profile and extent of intestinal damage in
      ulcerative colitis patients during clinical remission. METHOD: This is a cross
      sectional study in which body composition data (phase angle [PhA], fat mass [FM],
      triceps skin fold thickness [TSFt], mid-arm circumference [MAC], mid-arm muscle
      circumference [MAMC], adductor pollicis muscle thickness [APMt]), inflammatory
      profile (C-reactive protein [CRP], a1-acid glycoprotein, erythrocyte
      sedimentation rate [ESR]) and disease extent were recorded. RESULTS: The mean age
      of the 59 patients was 48.1 years; 53.3% were women. Most patients were in
      clinical remission (94.9%) and 3.4% was malnourished according to body mass
      index. PhA was inversely correlated with inflammatory markers such as CRP (R=
      0.59; p<0.001) and ESR (R=-0.46; p<0.001) and directly correlated with lean mass:
      MAMC (R=0.31; p=0.01) and APMt (R=0.47; p<0.001). Lean mass was inversely
      correlated with non-specific inflammation marker (APMt vs. ESR) and directly
      correlated with hemoglobin values (MAMC vs. hemoglobin). Logistic regression
      analysis revealed that body cell mass was associated with disease extent (OR
      0.92; 95CI 0.87-0.97; p<0.01). CONCLUSION: PhA was inversely correlated with
      inflammatory markers and directly correlated with lean mass. Acute inflammatory
      markers were correlated with disease extent. Body cell mass was associated with
      disease extent.

PMID- 29641663
TI  - The ORBITA trial: A point of view.
AB  - Treatment of stable coronary artery disease (CAD) relies on improved prognosis
      and relief of symptoms. National and international guidelines on CAD support the
      indication for revascularization in patients with limiting symptoms and
      refractory to drug treatment. Previous studies attested the efficacy of
      angioplasty to improve angina as well as the functional capacity of patients with
      symptomatic stable CAD. The ORBITA trial, recently published in an international
      journal, showed no benefit in terms of exercise tolerance compared to a placebo
      procedure in a population of single-vessel patients undergoing contemporary
      percutaneous coronary intervention. In this point of view article, the authors
      discuss the ORBITA trial regarding methodological issues, limitations and
      clinical applicability.

PMID- 29641661
TI  - Factors associated with maintenance of the use of internet, EpiFloripa Idoso
      longitudinal study.
AB  - OBJECTIVE: To describe the use of the internet and to identify the
      sociodemographic and health factors associated with changes in the use of the
      internet over four years in older adults participating in the Brazilian
      EpiFloripa Idoso study. METHODS: This is a longitudinal home-based, population
      based study with 1,197 older adults who live in the urban area of Florianopolis,
      State of Santa Catarina, Brazil. We applied a face-to-face interview. We describe
      the use of internet according to frequency, place, devices, and motives of the
      use of the internet. To identify factors associated with changes in the use of
      the internet, we categorized the outcome as: non-use of the internet, stopped
      using the internet, started using the internet, and kept using the internet. The
      independent variables were sex, age, family income, education level, family
      arrangement, marital status, presence of caregiver, paid work, and cognitive
      impairment screening. We used multinomial logistic regression with risk ratio
      (RR) estimates and their respective confidence intervals (95%CI). RESULTS: The
      prevalence of the use of internet increased from 22.9% in 2009-2010 to 26.6% in
      2013-2014. Of the total number of older adults who participated in the study,
      7.5% started using the internet, 3.2% stopped using it, 19.1% kept their use, and
      70.2% kept their non-use in the analyzed period. Of the older adults who used the
      internet, most used it every day or almost every day of the week, in their own
      home, on desktop or portable computers, mainly to send and receive messages, to
      search for information to learn or investigate something, to find information
      about goods and services, and to use news, social networking, and health
      information websites. The factors associated with the use of internet over four
      years were: being male (RR = 2.19, 95%CI 1.48-3.26), higher monthly family income
      (RR = 3.53, 95%CI 1.35-9.23), higher education level (RR = 2.64, 95%CI 1.57
      4.43), and no presence of caregiver (RR = 0.08, 95%CI 0.02-0.31). CONCLUSIONS:
      Although the use of the internet is increasing among older adults, most of the
      population is still digitally excluded, especially women with lower income and
      education level. Strategies that promote the digital inclusion of older adults
      should be stimulated, aiming to universalize the use of the internet, and they
      should take into account socioeconomic and gender inequalities.

PMID- 29641664
TI  - Maternal attachment and breastfeeding behaviors according to type of delivery in
      the immediate postpartum period.
AB  - INTRODUCTION: Breastfeeding is nutritious and has physiological benefits
      regarding the immunological aspect; also, it has an important role on maternal
      attachment and on raising a healthy baby. OBJECTIVE: Our study was conducted to
      analyze maternal attachment and breastfeeding behaviors in the immediate
      postpartum period of mothers who had vaginal and cesarean birth. METHOD: This
      descriptive and comparative study was conducted with women who sought the
      childbirth clinic of a university hospital in Izmir, Turkey. In the study, 175
      mothers were attended; 83 of them had vaginal birth and 92 had cesarean birth.
      Data were collected by using Demographic Identification Form, Maternal Attachment
      Inventory and LATCH Breastfeeding Assessment Score Tool. Descriptive and
      correlational statistics were used for data analysis. RESULTS: We found that
      Maternal Attachment Inventory and the LATCH breastfeeding charting system of
      mothers that had vaginal birth was higher than that of mothers who had cesarean
      delivery. There was a positive correlation between Maternal Attachment Inventory
      and LATCH total score average for both cesarean and vaginal birth. CONCLUSION:
      Mothers who delivered their babies by cesarean section had problems related to
      maternal attachment and breastfeeding more often than those who delivered
      vaginally.

PMID- 29641666
TI  - Subcutaneous emphysema, a different way to diagnose.
AB  - INTRODUCTION: Subcutaneous emphysema (SE) is a clinical condition that occurs
      when air gets into soft tissues under the skin. This can occur in any part of the
      body depending on the type of pathology. The most common site is under the skin
      that covers the chest wall or neck. It is characterized by painless swelling of
      tissues. The classic clinical sign is a crackling sensation upon touch,
      resembling that of touching a sponge beneath your fingers. OBJECTIVE: To describe
      a new way to diagnose subcutaneous emphysema. METHOD: Our finding was a matter of
      serendipity while inspecting a patient with subcutaneous emphysema using a
      stethoscope. Instead only hearing the patient's chest, the stethoscope was gently
      pressed against the skin with SE and so we were able to detect a different sound.
      RESULTS: This new way to diagnose subcutaneous emphysema consists in pressing the
      diaphragm part of stethoscope against the patient's skin where SE is supposed to
      be. Thus, we are able to hear a sound of small bubbles bursting. Crackle noise
      has an acoustic emission energy that varies between 750-1,200 Hz, considered high
      frequency. CONCLUSION: Although currently the use of imaging methods is
      widespread worldwide, we would like to strengthen the value of clinical
      examination. Auscultation is an essential diagnostic method that has become
      underestimated with the advances of healthcare and medicine as a whole. We
      therefore propose a different approach to diagnose SE.

PMID- 29641665
TI  - Individualized threshold for tumor segmentation in 18F-FDG PET/CT imaging: The
      key for response evaluation of neoadjuvant chemoradiation therapy in patients
      with rectal cancer?
AB  - INTRODUCTION: The standard treatment for locally advanced rectal cancer (RC)
      consists of neoadjuvant chemoradiation followed by radical surgery. Regardless
      the extensive use of SUVmax in 18F-FDG PET tumor uptake as representation of
      tumor glycolytic consumption, there is a trend to apply metabolic volume instead.
      Thus, the aim of the present study was to evaluate a noninvasive method for tumor
      segmentation using the 18F-FDG PET imaging in order to predict response to
      neoadjuvant chemoradiation therapy in patients with rectal cancer. METHOD: The
      sample consisted of stage II and III rectal cancer patients undergoing 18F-FDG
      PET/CT examination before and eight weeks after neoadjuvant therapy. An
      individualized tumor segmentation methodology was applied to generate tumor
      volumes (SUV2SD) and compare with standard SUVmax and fixed threshold (SUV40%,
      SUV50% and SUV60%) pre- and post-therapy. Therapeutic response was assessed in
      the resected specimens using Dworak's protocol recommendations. Several variables
      were generated and compared with the histopathological results. RESULTS:
      Seventeen (17) patients were included and analyzed. Significant differences were
      observed between responders (Dworak 3 and 4) and non-responders for SUVmax-2
      (p<0.01), SUV2SD-2 (p<0.05), SUV40%-2 (p<0.05), SUV50%-2 (p<0.05) and SUV60%-2
      (p<0.05). ROC analyses showed significant areas under the curve (p<0.01) for the
      proposed methodology with sensitivity and specificity varying from 60% to 83% and
      73% to 82%, respectively. CONCLUSION: The present study confirmed the predictive
      power of the variables using a noninvasive individualized methodology for tumor
      segmentation based on 18F-FDG PET/CT imaging for response evaluation in patients
      with rectal cancer after neoadjuvant chemoradiation therapy.

PMID- 29641667
TI  - Yellow fever.
AB  - The yellow fever (YF) virus is a Flavivirus, transmitted by Haemagogus, Sabethes
      or Aedes aegypti mosquitoes. The disease is endemic in forest areas in Africa and
      Latin America leading to epizootics in monkeys that constitute the reservoir of
      the disease. There are two forms of YF: sylvatic, transmitted accidentally when
      approaching the forests, and urban, which can be perpetuated by Aedes aegypti. In
      Brazil, the last case of urban YF occurred in 1942. Since then, there has been an
      expansion of transmission areas from the North and Midwest regions to the South
      and Southeast. In 2017, the country faced an important outbreak of the disease
      mainly in the states of Minas Gerais, Espirito Santo and Rio de Janeiro. In 2018,
      its reach extended from Minas Gerais toward Sao Paulo. Yellow fever has an
      incubation period of 3 to 6 days and sudden onset of symptoms with high fever,
      myalgia, headache, nausea/vomiting and increased transaminases. The disease
      ranges from asymptomatic to severe forms. The most serious forms occur in around
      15% of those infected, with high lethality rates. These forms lead to renal,
      hepatic and neurological impairment, and bleeding episodes. Treatment of mild and
      moderate forms is symptomatic, while severe and malignant forms depend on
      intensive care. Prevention is achieved by administering the vaccine, which is an
      effective (immunogenicity at 90-98%) and safe (0.4 severe events per 100,000
      doses) measure. In 2018, the first transplants in the world due to YF were
      performed. There is also an attempt to evaluate the use of active drugs against
      the virus in order to reduce disease severity.

PMID- 29641668
TI  - Asthma and occupation: Diagnosis using serial peak flow measurements.

PMID- 29641669
TI  - Impact of written information on control and adherence in type 2 diabetes.
AB  - INTRODUCTION: Diabetes therapeutic education and information by leaflets is
      important. This study aimed to understand the effectiveness of written
      information to diabetic patients, after six months, in the control of diabetes
      and medication adherence. METHOD: Non-pharmacological clinical trial. Randomized
      sample of diabetic patients of 65 volunteer doctors, distributed among the five
      health regions in Portugal. At the first appointment, patients were randomized in
      four groups (three intervention with validated leaflets and one control), leaflet
      reading being reinforced at the follow-up appointments in a 6-months period.
      Variables collected: HbA1c, home blood glucose, weight, waist circumference,
      blood pressure, cigarettes smoked, physical activity level, adherence to
      medication, medication, height, diabetes progression, age, sex and educational
      background. Descriptive and inferential statistics. RESULTS: From the 709
      patients recruited, 702 were studied in this 6-months period with no statistical
      differences in the baseline variables studied. After six months of intervention,
      the adherence to medication improved in the leaflet group (p=0.034). This was
      noticed in those under 65 years of age (p=0.027), with diabetes for <= 5 years
      (p=0.010), with educational background up to 4 years (p=0.030) and 9 years
      (p=0.006) and with HbA1c >= 7% at the beginning of the study. CONCLUSION:
      Interventions with leaflets handed in primary healthcare to people with diabetes
      type 2 can bring benefits in what concerns adherence to therapeutics, namely in
      younger people with a less studies.

PMID- 29641670
TI  - Special Dossier: "Scientific Evidence for Homeopathy".

PMID- 29641671
TI  - Postoperative local incision analgesia for acute pain treatment in patients with
      hepatocellular carcinoma.
AB  - OBJECTIVE: The present study aimed to investigate the analgesic effect and safety
      of using local incision analgesia to treat acute postoperative pain in patients
      with hepatocellular carcinoma (HCC). METHOD: A cohort of 60 patients undergoing
      liver cancer resection was randomly divided into three groups (n=20 per group):
      local incision analgesia (LIA) group, which received local infiltration with
      ropivacaine combined with a postoperative analgesia pump; intravenous patient
      controlled analgesia (PCA) group, which received fentanyl intravenous analgesia
      postoperatively; and the control group, which received tramadol hydrochloride
      injection postoperatively according to the NRS scoring system. The postoperative
      analgesic effect in each group was compared and tumor recurrence (survival) was
      analyzed using the Kaplan-Meier method. RESULTS: NRS scores, rate of analgesic
      usage, ambulation time (h) and intestinal function recovery time (h) were
      significantly reduced in LIA group compared with the control group at each
      postoperative time point (6, 12, 24 and 48 hours; p<0.05). Additionally, the NRS
      scores of LIA patients at 12 hours post-surgery was significantly reduced
      compared with PCA group (p<0.05), and the occurrence of postoperative adverse
      events in LIA group was significantly lower than that in PCA group (p<0.05).
      Survival analysis demonstrated that the mean survival time (tumor recurrence) was
      significantly increased in LIA group compared with the control group (chi2=4.749;
      p=0.029). CONCLUSION: Local incision analgesia improves the analgesic effect,
      causes fewer adverse reactions and increases postoperative survival time. Our
      study demonstrated that local incision analgesia is a safe and effective method
      of postoperative pain management following hepatectomy.

PMID- 29641672
TI  - Assessing cardiovascular risk in ATM heterozygotes.
AB  - OBJECTIVE: To evaluate the carotid intima-media complex (CIMC) thickness and
      lipid metabolism biomarkers associated with cardiovascular risk (CR) in parents
      of patients with ataxia-telangiectasia and verify an association with gender.
      METHOD: A cross-sectional and controlled study with 29 ATM heterozygotes and 14
      healthy controls. Biochemical tests and CIMC thickness measurement were
      performed. RESULTS: The mean CIMC measurement in heterozygous ATM was 0.72 +/-
      0.1 mm (minimum: 0.5 mm and maximum: 1.0 mm). Noticed high percentage of amounts
      above 75 percentile compared to the population referential (16 [76.2%]), without
      any significant statistical differences between the female and the male gender
      (11/15 [73.3%] vs. 5/6 [83.3%]; p=0.550). The comparison between heterozygous and
      controls, stratified by gender, showed that in heterozygous ATMs, women had
      higher concentrations of HDL-c compared to men, as well as higher values of hs
      CRP in relation to the control women. In heterozygous ATMs, stratified by gender,
      the correlation between HDL-c and hs-CRP was inversely proportional and stronger
      among women, with a tendency to statistical significance. CONCLUSION:
      Heterozygous ATMs did not differ from controls in relation to the biomarkers
      studied related to CR. However, most of them presented increased CIMC,
      independent predictor of death, risk for myocardial infarction and stroke,
      compared to the referential for the same age group. This finding suggests CR in
      the heterozygous ATM and shows to the need to monitor CIMC thickness and
      nutritional orientations.

PMID- 29641673
TI  - Assessment of the prescription of red blood cell concentrates in the pediatric
      age group.
AB  - OBJECTIVE: To verify the adequacy of red blood cell (RBC) prescription to
      pediatric patients in different sectors of a pediatric hospital. METHOD: A
      retrospective study was conducted including 837/990 RBC transfusion requisition
      forms for children and adolescents (0 to 13 years old) filed in between January
      2007 and April 2015 by the pediatricians of the emergency room (ER), infirmary
      ward and intensive care unit (pICU). Transfusion requisition forms belonging to
      patients with chronic anemia or acute hemorrhage, as well as incompletes
      requisition forms, were excluded. RESULTS: Trigger, prescribed volume and subtype
      of RBC concentrates were adequate in 532 (65.3%), 460 (58.8%) and 805 (96.2%) of
      the transfusions, respectively. When the clinical picture was considered,
      prescription adequacy was higher compared to the use of the hemoglobin level
      alone (70.9% vs. 41%). The pICU had the highest correct trigger percentage (343
      [71.6%]; p<0.001) while the ER showed more often adequate prescribed volumes (119
      [66.1%]; p=0.020). The most common inadequacy regarding volume was that of
      prescriptions above the recommendation > 15 mL/kg found in 309 cases (36.9%).
      Thirty-two (32) RBC subtypes were requested and none were consistent with current
      recommendations. CONCLUSION: The results obtained in our study showed that RBC
      transfusion occurred more appropriately when the clinical picture was taken into
      account at request. There was a tendency to prescribe higher volumes and RBC
      subtypes without the justification of current protocols. Hemotherapic teachings
      at undergraduate level and medical residency must be improved.

PMID- 29641674
TI  - Assessment of the prevalence of vertical hepatitis B transmission in two
      consecutive generations.
AB  - INTRODUCTION: Hepatitis B is an important public health problem in the world and
      one of the forms of contagion would be through vertical transmission. Precose
      diagnosis allows the adoption of prophylaxis measures, which results in
      prevention in more than 90% of cases. OBJECTIVE: To describe the prevalences of
      vertical transmission and compare two generations (mother/patient and
      patient/child). METHOD: This was a cross-sectional study, which included 101
      patients. The interviews were performed through the application of the instrument
      of data collection and information of the physical file before the medical
      consultation. RESULTS: The mean +/- SD of age was 50.9 +/- 13.1 years, the male
      gender predominated, with 56.4% of the patients, and the predominance was white,
      with 43.6%. Vertical transmission between mother and patient occurred in 17.8%
      and between patient and child, in 7.9%. In all of the eight cases of vertical
      transmission, the diagnosis was after the birth of children infected with HBV,
      and in 3/8 (37.5%), there was more than one case of infection by this mechanism
      per patient, totaling 13 children with the disease. CONCLUSION: There was a
      reduction in vertical transmission, showing that preventive measures were
      effective.

PMID- 29641675
TI  - Pseudomyxoma peritonei in a pediatric patient: A case report and literature
      review.
AB  - INTRODUCTION: Pseudomyxoma peritonei (PMP) is a rare clinical condition, with an
      incidence of 1-2 cases per million, characterized by the dissemination of
      mucinous implants on the peritoneal surface and progressive gelatinous ascites.
      Although it usually presents an indolent behavior, its non-specific clinical
      presentation contributes to many cases remaining undiagnosed until a laparotomy
      is performed. With late diagnosis, performed after a long period of clinical
      deterioration and disease progression, it is common to find complications such as
      the formation of intestinal fistulas and obstruction. METHOD: Review of the
      medical record and search for references in the Medline, Lilacs, SciELO and MD
      Consult databases. RESULTS: There are rare case reports found in the literature
      demonstrating atypical PMP presentations. Our report is that of a 17-year-old
      adolescent with a sporadic tumor diagnosed in a primary site in the transverse
      colon, contrary to data commonly found in the literature that mention a more
      frequent occurrence in women in the fifth decade of life and with a primary site
      in the ovary and appendix. The development of mucinous adenocarcinoma is rare in
      the pediatric population, and topography in the transverse colon and non-familial
      sporadic pattern are unusual. CONCLUSION: The case reported not only raises
      awareness about the atypical presentations of the disease, but also emphasizes
      the use of imaging examinations for diagnosis, which has an important impact on
      prognosis and survival if performed timely.

PMID- 29641676
TI  - Heat-not-burn and electronic cigarettes: Truths and untruths about harm
      reduction.

PMID- 29641677
TI  - Use of illicit drugs by adolescents and young adults of an urban settlement in
      Brazil.
AB  - OBJECTIVE: To estimate the prevalence and factors associated with illicit drug
      use by adolescents and young adults of a formal urban settlement. METHOD: Cross
      sectional study including adolescents and young adults 12-24 years of an urban
      settlement in the Midwest Region of Brazil. Data were collected using a
      structured questionnaire and analyzed using Stata, version 12.0. We used Poisson
      regression model to estimate the factors associated with illicit drug use.
      RESULTS: Of the total participants (n=105), 27.6% (95CI 20.0-36.9%) had used
      illicit drugs such as marijuana, cocaine, crack, LSD and inhalants. The
      consumption of these substances was associated with male gender, use of body
      piercing and/or tattoos, licit drug use and self-report of signs and/or symptoms
      of sexually transmitted infections. CONCLUSION: High prevalence of illicit drug
      use was found in the individuals investigated, ratifying the presence of risk
      factors to the vulnerability of the settlers to use these substances in the urban
      settlement population.

PMID- 29641678
TI  - Comparative study of computed tomography (CT) and pathological diagnosis toward
      mediastinal lymph node metastasis in esophageal carcinoma.
AB  - OBJECTIVE: To investigate the diagnostic criteria of mediastinal lymph node
      metastasis (MLNM) in esophageal carcinoma (EC) by comparing the lymph node sizes
      measured by computed tomography (CT) and obtained by postoperative pathological
      examination. METHOD: A total of 305 EC patients were selected. MLNM location,
      shortest diameter and number were investigated one week before surgery, and then
      compared with their pathological findings. RESULTS: The receiver operating
      characteristic (ROC) curve analysis revealed that the minimum diameters of MLNM
      in the thoracic cavity was 8 mm (area under curve [AUC] = 0.766, Youden index =
      0.424), 5 mm in supraclavicular fossa (AUC = 0.785, Youden index = 0.494), 6 mm
      in tracheoesophageal groove (AUC = 0.755, Youden index = 0.405); the sensitivity
      was increased significantly, and the Youden index was increased significantly
      when compared with 10 mm. CONCLUSION: The shortest diameter of diagnostic
      criteria of lymph nodes in EC could be less than 10 mm on CT.

PMID- 29641679
TI  - Combination of topical agents and oxybutynin as a therapeutic modality for
      patients with both osmidrosis and hyperhidrosis.
AB  - INTRODUCTION: The association of osmidrosis and hyperhidrosis often causes
      emotional and social problems that may impair the patients' quality of life. The
      purpose of our study was to analyze the therapeutic results of oxybutynin and
      topical agents in 89 patients with both osmidrosis and hyperhidrosis. METHOD: We
      conducted an observational study at two specialized centers of hyperhidrosis
      between April 2007 and August 2013. Eighty-nine (89) patients with both
      osmidrosis and hyperhidrosis were treated with oxybutynin and topical agents.
      Patients were evaluated before treatment and at 3 and 6 weeks after treatment
      started, by using the Quality of Life Questionnaire and the Sweating Evolution
      Scale. RESULTS: Before treatment, 98% of the patients presented with poor or very
      poor quality of life. After six weeks of treatment, 70% stated their quality of
      life as being slightly better or much better (p<0.001) and nearly 70% of the
      patients experienced a moderate or great improvement in sweating and malodor.
      Improvement in osmidrosis was significantly greater when the axillary region was
      the first most disturbing site of hyperhidrosis. CONCLUSION: There was a
      significant improvement in quality of life and a reduction in sweating and
      malodor after six weeks of treatment with topical agents and oxybutynin in
      patients with both hyperhidrosis and osmidrosis. Therefore, clinical treatment
      should be considered before invasive techniques.

PMID- 29641681
TI  - Strategies for identification and coping with the violence situation by intimate
      partners of pregnant women.
AB  - Objective To know the strategies used by nurses of Units of Family Health
      Strategies to identify and cope with the violence situation by intimate partners
      of pregnant women. Method Descriptive study with a qualitative approach, in which
      semi-structured interviews were conducted with 23 primary care nurses from
      September 2015 to April 2016. Thematic content analysis was used. Results The
      category "It's very complex" has emerged - actions to identify and cope with the
      violence situation by intimate partners of pregnant women. Physical injuries were
      the main violence indicative identified at prenatal care. The coping strategies
      were the referrals to specialized services and joint discussion with healthcare
      team. Conclusion There's a need to organize a nursing protocol that helps in the
      identification and classification of risk exposure to violence, permanent
      education of these professionals and strengthening of intersectoral actions.

PMID- 29641680
TI  - Nonalcoholic steatohepatitis in posttransplantation liver: Review article.
AB  - INTRODUCTION: Nonalcoholic steatohepatitis (NASH) associated or not with
      cirrhosis is the third leading indication for liver transplantation (LT) around
      the world. After transplants, NASH has a high prevalence and occurs as both
      recurrent and de novo manifestations. De novo NASH can also occur in allografts
      of patients transplanted for non-NASH liver disease. OBJECTIVE: To evaluate
      recurrent or de novo NASH in post-LT patients. METHOD: A literature review was
      performed using search engines of indexed scientific material, including Medline
      (by PubMed), Scielo and Lilacs, to identify articles published in Portuguese and
      English until August 2016. Eligible studies included: place and year of
      publication, prevalence, clinical characteristics, risk factors and survival.
      RESULTS: A total of 110 articles were identified and 63 were selected. Most of
      the studies evaluated recurrence and survival after LT. Survival reached 90-100%
      in 1 year and 52-100% in 5 years. Recurrence of NAFLD (steatosis) was described
      in 15-100% and NASH, in 4-71%. NAFLD and de novo NASH were observed in 18-67% and
      3-17%, respectively. Metabolic syndrome, diabetes mellitus, dyslipidemia and
      hypertension were seen in 45-58%, 18-59%, 25-66% and 52-82%, respectively.
      CONCLUSION: After liver transplants, patients present a high prevalence of
      recurrent and de novo NASH. They also show a high frequence of metabolic
      disorders. Nevertheless, these alterations seem not to influence patient
      survival.

PMID- 29641682
TI  - Perception of nursing regarding patient safety climate in public and private
      institutions.
AB  - Objective To evaluate the perception of nursing staff regarding the safety
      climate among healthcare professionals from public and private institutions.
      Method This is a cross-sectional, quantitative study conducted with 235 nursing
      professionals from a private hospital and a public hospital in Campinas, between
      October 2014 and October 2015. The Safety Attitudes Questionnaire - Short Form
      was used to collect data. Descriptive and inferential statistics were used for
      analysis, and the Mann-Whitney test was used to compare the institutions. Results
      The private institution had higher averages than the public institution, and
      significant differences in the areas of safety climate (p=0.00), unit management
      (p<0.0001), hospital management (p=<0.0001), working conditions (p=<0.0001), and
      teamwork (p=0.00). Conclusion Although the private institution performed better,
      the professionals perceived the safety climate as unsatisfactory in both
      institutions.

PMID- 29641683
TI  - Factors associated with cesarean sections in a high complexity university
      hospital in southern Brazil.
AB  - Objective To identify the factors associated with cesarean sections in a high
      complexity university hospital in southern Brazil. Methods Cross-sectional study
      carried out at the Obstetric Hospital Unit of the Hospital de Clinicas de Porto
      Alegre. Data were gathered from questionnaires carried out with 361 puerperal
      women and maternal and neonatal records, from February to April 2013. For the
      analysis, Prevalence Ratio through Univariate Poisson Regression was used.
      Results The prevalence of cesarean sections was 31%. The category of
      hospitalization, cervix dilation and its characteristics, fetal presentation, and
      uterine dynamics, at the time of admission, were statistically related to
      cesarean sections; not having a previous cesarean section and night shift (from
      midnight to 6AM) were protective factors. Conclusions The prevalence of cesarean
      sections is above the rate recommended by the World Health Organization, but it
      is similar to rates found in other university hospitals, thus pointing out the
      need for the proposition of actions aimed at improving this indicator.

PMID- 29641684
TI  - Quality assessment of a system of prenatal information.
AB  - Objective To evaluate the quality of the Prenatal Information System of the city
      of Vitoria - ES. Methods This is a cross-sectional study with an analysis of the
      Prenatal Information System Data (SISPRENATAL) from a municipality in the
      Southeast Region of Brazil. The quality of the system was evaluated according to
      the accessibility criteria, methodological clarity, timeliness and completeness
      defined by the Economic Commission for Latin America and the Caribbean (ECLAC).
      Completeness was evaluated according to the criteria of incompleteness proposed
      by Romero and Cunha, and assigned scores in degrees of evaluation for: excellent,
      good, fair, bad and very bad. Results Most of the results presented scores of bad
      and very bad quality. Fields with excellent or good quality for incompleteness
      are related to the mandatory items. Conclusion Professionals need to be aware of
      the proper registration of the care provided to pregnant women.

PMID- 29641685
TI  - Factors associated with foot ulceration of people with diabetes mellitus living
      in rural areas.
AB  - Objective To analyze the factors associated with the risk of ulceration in the
      feet of people with diabetes mellitus living in rural areas. Methods This is a
      cross-sectional study conducted with 293 individuals with diabetes mellitus, aged
      40 years or older, living in the south of Brazil, in 2014. We analyzed
      socioeconomic variables, clinical conditions and foot self-care. We used the
      Poisson multiple regression model and the Prevalence Ratio (PR) and p-value<0.05
      as a measure of association. Results 43.7% of the sample presented risk of foot
      ulceration. The highest prevalence of foot ulceration risk was associated with
      people with lower purchasing power (PRadjusted=1.62/IC95%:1.52-2.22), with
      retinopathy (PRadjusted=1.30/IC95%:1.12-1.68) and alteration in foot moisture
      (PRadjusted=1.57/IC95%:1.22-2.01). We identified low education level (64.2%),
      high prevalence of arterial hypertension (86.3%) and onychomycosis in the feet
      (72%). Conclusions Diabetic patients need an assessment of the risk of foot
      ulceration, especially those with longer diagnosis, chronic complications and low
      socio-educational level.

PMID- 29641686
TI  - Risk factors in the domestic environment for falls in children under five years
      of age.
AB  - Objective To analyze the risk factors in the domestic environment for the
      occurrence of falls in children under five years of age. Method A cross-sectional
      study was conducted in May and in June of 2016 with 344 caregivers of children
      from Northeast Brazil. A socio-economic questionnaire and a checklist for
      environmental observation were used. Bivariate analyzes were performed using
      Pearson's Chi-square test. Results They were associated with the risk of falls in
      children under 5 years of age: High net (p = 0.015), presence of stairs or steps
      without a handrail (p=0.003), and exits and passages kept with toys, furniture,
      boxes or other items that may be obstructive (p=0.002). Conclusion The factors in
      the domestic environment identified as associated with the risk of falls in
      children under five years of age demonstrate that there is a need to construct
      prevention strategies related to the structure and organization of this
      environment.

PMID- 29641687
TI  - Analysis of work capacity and stress among nursing professionals with
      musculoskeletal disorders.
AB  - Objective To characterize the sociodemographic aspects, work capacity and stress
      of nursing workers affected by musculoskeletal disorders and to analyze the
      association between musculoskeletal comorbidities, capacity, stress and social
      support. Methods Cross-sectional study, conducted in two hospitals in Manaus. The
      Work Capacity Index and the Job Stress Scale were used, translated and validated
      in nursing workers for more than one year, with musculoskeletal pain in the last
      three months, with a minimum duration of two hours. Results The study had a
      majority of women and technicians, aged 42 +/- 10.7 years, with moderate capacity
      (34.7 +/- 5.11) associated with musculoskeletal comorbidities. The stress
      affected 56% and the capacity correlated weak and inverse to stress and direct to
      the social support. Conclusions There was a predominance of women and
      technicians, and musculoskeletal pain was associated with a decrease in capacity.
      Social support was associated with increased capacity and decreased stress.

PMID- 29641688
TI  - Object and technologies in the working process of an itinerant team in mental
      health.
AB  - Objective To analyze the work object and the technologies in the working process
      of a Mental Health Itinerant Team in the attention to drug users. Methods
      Qualitative case study, carried out in a municipality in the South of Brazil. The
      theoretical framework was the Healthcare Labor Process. The data was collected
      through participant observation and semi-structured interviews with the
      professionals of an itinerant team in the year of 2015. For data analysis we used
      the Thematic Content Analysis. Results In the first empirical category - work
      object - the user is considered as a focus, bringing new challenges in the team's
      relationship with the network. In the second category - technologies of the work
      process - potentialities and contradictions of the team work tools are
      highlighted. Conclusions As an innovation in the mental health context, the
      itinerant team brings real possibilities to reinvent the care for the drug user
      as well as new institutional challenges.

PMID- 29641689
TI  - Validation of a nursing report for a pediatric intensive care unit.
AB  - Objective To validate the Nursing Report for a pediatric intensive care unit
      regarding its appearance and content. Methods A methodological study regarding
      the validation of a nursing report for a teaching hospital in the Northwest
      region of Parana. The instrument, built in a previous stage, was elaborated with
      information obtained in a review of pertinent literature and empirical evidence
      pointed out by nurses who experience these units. The temporary version was
      submitted to a board of evaluators (March-November/2014), whose expertise
      contributed to the evaluation process of appearance and content (analysis,
      rearrangement, refinement, finalization). Results The Pertinence of Content
      criterion, relative to the topics of the instrument, reached the highest levels
      of agreement among the evaluators (78-100%). The topics that did not reach the
      pre-defined agreement level were replaced, excluded or reformulated. The
      restructured instrument was revalued by the evaluators, obtaining satisfactory
      agreement levels in all the criteria (78-100%). Conclusions The final version was
      validated in terms of appearance and content, and is suitable to be used.

PMID- 29641690
TI  - Influence of curricular reforms in mental health nursing education between 1969
      and 2014.
AB  - Objective To analyze the influence of curricular changes in mental health nursing
      education at the Federal University of Santa Catarina. Method Qualitative
      research, exploratory and descriptive. Data were collected in official ordinances
      in the Pedagogical Projects of the Nursing Course and in the Teaching Plans in
      the period from 1969 to 2014. The data collection was carried out between the
      months of March and December 2015. We used a spreadsheet to organize the data and
      they were analyzed according to the technique of documentary analysis. Results
      Trends in curricular changes were highlighted after the Curricular and
      Psychiatric Reforms. The most significant changes occurred since 2004 with the
      National Curriculum Guidelines and Law 10.2016. Conclusion It was found that the
      curricular changes occurred from induction and from outside the educational
      institution policies. The influences resulted in changes in the name of courses,
      course offerings and course objectives, and integration between courses and
      practical settings, among others.

PMID- 29641691
TI  - Mycetomas: an epidemiological, etiological, clinical, laboratory and therapeutic
      review.
AB  - Mycetoma is a chronic suppurative disease of the skin and subcutaneous tissue,
      characterized by a symptomatic triad: tumor, fistulas and grains. It can be
      caused by fungi (eumycetoma) and bacteria (actinomycetoma), with similar clinical
      features. Diagnosis is based on the clinical presentation and identification of
      the etiological agents in the tissue, by mycological/bacteriological,
      histopathological and immunohistochemical tests. It is important to specify the
      fungal or bacterial etiology, because the treatments are different. An approach
      that involves early diagnosis, the use of systemic antibiotics or antifungal
      agents, including surgical removal of lesions, is the basis for the treatment of
      these diseases. In this review, the most commonly used diagnostic methods and
      treatments will be discussed. Also, we will review the history of the disease
      through epidemiological and etiological aspects.

PMID- 29641692
TI  - Prognostic factors for metastasis in cutaneous melanoma.
AB  - BACKGROUND: Melanoma is a malignant neoplasia that shows high mortality when
      diagnosed in advanced stages. Early identification of high-risk patients for the
      development of melanoma metastases is the main strategy to reduce mortality.
      OBJECTIVE: To assess the influence of eight epidemiological and histopathologic
      features on the development of metastases in patients diagnosed with primary
      cutaneous melanoma. METHODS: Our historical cohort comprised patients with
      invasive primary cutaneous melanoma seen between 1995 and 2012 at a public
      university hospital and a private oncologic surgery institution in Southeastern
      Brazil. The following variables were analyzed: gender, age, family history of
      melanoma, site of the primary tumor, clinical and histologic subtype, Breslow
      thickness, histologic ulceration and the mitotic index. Kaplan-Meier univariate
      test and multivariate Cox proportional hazard analysis were used to assess
      factors associated with disease-free survival. RESULTS: Five hundred and fourteen
      patients were enrolled. The univariate analysis identified the following
      significant risk factors: gender, age, site of the tumor, clinical and histologic
      subtype, Breslow thickness, histologic ulceration and mitotic index. Multivariate
      analysis included 244 patients and detected four significant prognostic factors:
      male gender, nodular clinical and histologic subtype, Breslow thickness > 4mm,
      and histologic ulceration. The mitotic index was not included in this analysis.
      STUDY LIMITATIONS: Small number of patients in multivariate analysis.
      CONCLUSIONS: The following prognostic factors to the development of melanoma
      metastasis were identified in the study: male gender, nodular histologic subtype,
      Breslow thickness > 4mm and ulceration.

PMID- 29641693
TI  - Occupational dermatoses reported in Brazil from 2007 to 2014.
AB  - BACKGROUND: Occupational diseases are very prevalent in the world, especially in
      developing countries. Occupational dermatoses are responsible for most of these
      cases. However, epidemiological studies are rare in Brazil. OBJECTIVES: To verify
      the panorama of occupational skin diseases in Brazil describing frequencies of
      work-related dermatoses and their sociodemographic and occupational patterns.
      METHODS: We used retrospective data from the Notifiable Diseases Information
      System, (from 2007-2014) tabulated with the Tab program for Windows - TabWin12.
      We used intentional non-probability sampling and sequential selection,
      considering all notified occupational dermatoses. RESULTS: All cases of
      occupational dermatoses referred to in the period were analyzed (n = 4710). Males
      and the age group of 35-49 years were the most affected. The most affected body
      area was the upper limb (34.2%) and the hand (25.4%). The "causative agent" field
      in the forms was not filled in 69.4% of cases, with chrome as the most prevalent
      cause reported (11.8%). ICD-10 codes more prevalent were L23, L24, and L25,
      corresponding to 34.2% of the sample. In total, 29% of patients needed to take a
      sick leave. No cases evolved to death and there were 0.2% of total as permanent
      disability. STUDY LIMITATIONS: The amount of missing information for various
      items in the system draws attention. CONCLUSIONS: Treatment of patients with
      occupational dermatitis include the identification and removal of the causative
      agent and specific treatment of the disease. Diagnosis delay in cases of
      occupational dermatoses brings social and financial consequences to the work and
      life of workers.

PMID- 29641694
TI  - The efficacy and safety of phototherapy in geriatric patients: a retrospective
      study.
AB  - BACKGROUND: While phototherapy is a well-established treatment for many
      dermatoses, data from the literature regarding its use in elderly patients are
      quite limited. OBJECTIVE: In this study, we aimed to determine the phototherapy
      indications in geriatric patients and to evaluate the effectiveness and
      reliability of phototherapy in this group. METHODS: This study included 95
      patients of 65 years of age and older who were treated in our phototherapy unit
      between 2006 and 2015. The data for this study were collected retrospectively
      from patient follow-up forms in the phototherapy unit. RESULTS: Phototherapy was
      administered to 28 (29.5%) patients for mycosis fungoides, 25 (26.3%) patients
      foplaque type psoriasis, 12 (12.6%) patients for palmoplantar psoriasis, 12
      (12.6%) patients for generalized pruritus, and 18 (19%) for other dermatoses. Of
      the patients, 64.2% had received a narrowband UVB (NB-UVB), 21.1% oral psoralen
      UVA (PUVA), and 14.7% local PUVA treatment. A complete response was achieved in
      76.9-85.7% of the mycosis fungoides and in 73.71-100% of the psoriasis vulgaris
      patients treated with NB-UVB and PUVA, respectively. All the patients with
      generalized pruritus were treated with NB-UVB, and 80% of these patients achieved
      significant improvement. The erythema rate was found to be 0.43% per session for
      NB-UVB treatment and 0.46% per session for PUVA treatment as a side effect. STUDY
      LIMITATIONS: The limitations of our study are that it was retrospective and the
      remission durations of the patients are not known. CONCLUSION: This study showed
      that phototherapy is effective and reliable in the elderly population with proper
      dose increases and close follow-up.

PMID- 29641696
TI  - Epidemiological and histopathological aspects of primary cutaneous melanoma in
      residents of Joinville, 2003-2014.
AB  - BACKGROUND: The worldwide incidence of cutaneous melanoma (CM) has been
      continuously increasing over the last decades. Primary and secondary prevention,
      with attention to risk factors and early diagnosis, remain the cornerstone for
      reducing the burden of cutaneous melanoma. Detailed information with respect to
      clinical and pathological data on cutaneous melanoma is scarce in Brazil.
      OBJECTIVE: The purpose of our study was to analyze epidemiological and
      pathological characteristics of primary cutaneous melanoma in Joinville, southern
      Brazil. METHODS: Observational, cross-sectional, retrospective study in which 893
      reports of primary cutaneous melanoma from the local population were analyzed in
      the period 2003-2014. The study was approved by the local Ethics and Research
      Committee. RESULTS: We observed a female predominance of cutaneous melanoma
      (56.3%). The age standardized incidence rate of primary cutaneous melanoma for
      the world population in the period 2003-06 was 11.8 per 100,000 population (CI
      95%, 10.3-13.4), and 17.5 (CI 95%, 15.7-19.3) in 2011-14, revealing a significant
      increase of 48.3% (p < 0,05). Six and a half percent of patients had multiple
      cutaneous melanomas (mean 2.2 years and a maximum of 10.0 years between
      diagnoses). We observed significant differences between the location head/neck
      and cutaneous melanoma in situ, lower limb with Breslow depth S III and upper
      limb with Breslow depth S I. The comparison of the characteristics of cutaneous
      melanoma in the elderly and non-elderly (< 60 years old) showed significant
      differences with respect to all the variables studied. STUDY LIMITATIONS: Using
      secondary data source. CONCLUSION: Joinville has high incidence coefficients for
      Brazilian standards, showing an increase in the incidence of cutaneous melanoma.

PMID- 29641695
TI  - Photoprotection in adolescents: what they know and how they behave.
AB  - BACKGROUND: The greatest sun exposure occurs until adolescence and this is the
      only factor involved in photocarcinogenesis subject to modification with
      photoprotection. OBJECTIVE: The objective of this study was to evaluate the
      habits and knowledge of adolescents regarding photoprotection. METHOD: Cross
      sectional study that included 512 students from primary and high school. Data
      were collected by questionnaires with questions about habits and knowledge on sun
      protection. For data analysis, Pearson's Chi-square test and Yates test were
      applied, with 5% level of significance. RESULTS: We evaluated 512 students, with
      a mean age of 14 years old. The teenagers agreed that ultraviolet rays cause skin
      cancer and aging (96% and 70%, respectively). Knowledge about the occurrence of
      burns even on cloudy days was recorded in 68% of cases, as well as the need for
      photoprotection for sports in 72%. The source of information about sun protection
      were by parents in 55%. In 70% was observed previous occurrence of sunburn, the
      daily use of sunscreens was found in 15% and 67% used only at the beach. of
      sunscreens with SPF higher than 30 was reported by 70% of students and 57%
      reported going to the beach between 10h and 16h. In 68% of cases it was
      registered insufficient sun protection, attributed, in 57% of the time to
      forgetfulness. STUDY LIMITATIONS: The sample refers to two schools of Curitiba
      (PR), Brazil. CONCLUSION: Teenagers know the risks of sun exposure, but they do
      not adopt the practices for adequate protection.

PMID- 29641697
TI  - A study of the association of glutathione S-transferase M1/T1 polymorphisms with
      susceptibility to vitiligo in Egyptian patients.
AB  - BACKGROUND: The association of glutathione S-transferases M1/T1 (GSTM1/T1) null
      polymorphisms with vitiligo was proposed in several studies including two
      Egyptian studies with contradictory results. OBJECTIVE: The aim here was to
      assess the association between GSTM1/T1 null polymorphisms and the susceptibility
      to vitiligo in a larger sample of Egyptian patients with generalized vitiligo.
      METHODS: This study included 122 vitiligo patients and 200 healthy controls that
      were age, and gender matched. Assessment of GSTM1/T1 gene polymorphisms was done
      using a multiplex polymerase chain reaction (PCR). RESULTS: Increased odds of
      generalized vitiligo was observed with the null genotypes of GSTM1 and GSTT1
      polymorphisms (P<0.05). Controls with GSTM1 null/GSTT1+ heterozygosis presented
      with a 2.97 odds protection from having generalized vitiligo (OR=2.97, 95%CI=1.1
      7.7) (P=0.02) compared with patients. STUDY LIMITATIONS: Small sample size of
      patients. CONCLUSIONS: This study showed a significant trend towards an
      association with the combination of the GSTM1/GSTT1 double null polymorphism and
      generalized vitiligo. Individuals with GSTM1 null/GSTT1+ heterozygosis have a
      2.97 odds protection from having generalized vitiligo compared with patients. It
      was is the first time, to our knowledge, that such an association has been
      reported.

PMID- 29641698
TI  - Nickel, chromium and cobalt: the relevant allergens in allergic contact
      dermatitis. Comparative study between two periods: 1995-2002 and 2003-2015.
AB  - BACKGROUND: Metals are common agents of allergic contact dermatitis, occupational
      or not, with decreasing incidence over the last years in some countries that have
      regulated the amount of nickel in objects. OBJECTIVES: To analyze and compare
      with previous studies the profile of metal sensitization between 2003-2015.
      METHODS: Patients who underwent patch testing between 2003-2015 were evaluated
      retrospectively regarding the sensitization rates to metals, the associations
      between them, the relationship with profession and epidemiology. RESULTS: Of the
      1,386 patients tested, 438 (32%) had positive test to some metal, similar results
      to the 404/1,208 (33%) of the previous study (1995-2002) performed at the same
      service (p=0.32). The frequency of nickel (77%), cobalt (32%) and chromium (29%)
      changed slightly (p=0.20). Most cases of sensitization to chromium were related
      to the occupation (64%), in contrast to nickel and cobalt (p<0.0001). There was a
      predominance of females among those sensitized to metal in both studies (p=0.63)
      and the age group of 20-49 years old (p=0.11); the number of fair-skinned
      individuals increased (p<0.001), as well as the lesions in the cephalic segment
      (50.5%; p<0.0001) and hands (45%; p<0.0001), which are not the most frequent
      location anymore. The number of cleaners decreased (39% vs. 59%; p<0.0001), which
      still lead in front of bricklayers/painters, which increased (14% vs. 9%;
      p=0.013). The frequency of wet work reduced (65% vs. 81%; p<0.0001). STUDY
      LIMITATIONS: The study included a single population group; only patients with
      positive tests to metals were considered - the others were not evaluated for the
      possibility of false negatives. CONCLUSION: The sensitization to metals,
      occupational or not, has been significant over the last 21 years, with few
      epidemiological changes.

PMID- 29641700
TI  - Application of dermoscopy image analysis technique in diagnosing urethral
      condylomata acuminata.
AB  - BACKGROUND: In this study, cases with suspected urethral condylomata acuminata
      were examined by dermoscopy, in order to explore an effective method for
      clinical. OBJECTIVE: To study the application of dermoscopy image analysis
      technique in clinical diagnosis of urethral condylomata acuminata. METHODS: A
      total of 220 suspected urethral condylomata acuminata were clinically diagnosed
      first with the naked eyes, and then by using dermoscopy image analysis technique.
      Afterwards, a comparative analysis was made for the two diagnostic methods.
      RESULTS: Among the 220 suspected urethral condylomata acuminata, there was a
      higher positive rate by dermoscopy examination than visual observation. STUDY
      LIMITATIONS: Dermoscopy examination technique is still restricted by its
      inapplicability in deep urethral orifice and skin wrinkles, and concordance
      between different clinicians may also vary. CONCLUSION: Dermoscopy image analysis
      technique features a high sensitivity, quick and accurate diagnosis and is non
      invasive, and we recommend its use.

PMID- 29641701
TI  - Hyaluronic acid in dermatomyositis and polymyositis: relationship with disease
      and cutaneous lesions.
AB  - BACKGROUND: There are scarce studies in the literature about hyaluronic acid in
      systemic autoimmune myopathies. OBJECTIVES: To analyze the serum level of
      hyaluronic acid in patients with dermatomyositis and polymyositis. METHODS: Cross
      sectional study, single-center, that evaluated hyaluronic acid in 18
      dermatomyositis and 15 polymyositis (Bohan and Peter criteria), newly diagnosed,
      with clinical and laboratory activity, with no previous drug treatment. The
      patients were also age-, gender- and ethnicity-matched to 36 healthy individuals.
      The hyaluronic acid was analyzed by ELISA/EIA kit anti-hyaluronic acid. RESULTS:
      There was a higher serum level of hyaluronic acid in patients with autoimmune
      myopathies, in relation to control group (P<0.05). Moreover, the serum level of
      this glycosaminoglycan was higher in dermatomyositis, when compared to
      polymyositis. Both groups were comparable with regard to demographic, clinical
      and laboratory data, except for the presence of skin lesions in the first group.
      STUDY LIMITATIONS.: The presence of hyaluronic acid in cutaneous lesions,
      particularly of patients with dermatomyositis, was not analyzed neither
      quantified. In addition, due to disease rarity and the establishment of strict
      inclusion and exclusion criteria, there was a small sample in the present study.
      CONCLUSIONS: As an example of others systemic autoimmune diseases, it is possible
      that the hyaluronic acid is involved in the pathogenesis of autoimmune
      myopathies, and particularly when associated with cutaneous lesions.

PMID- 29641699
TI  - The potential role of Th17 lymphocytes in patients with psoriasis.
AB  - BACKGROUND: Psoriasis is a chronic inflammatory disorder, characterized by
      increased keratinocyte proliferation due to abnormal differentiation of basal
      keratinocytes. The etiology of the disease is unclear, and according to the
      survey results, it is hypothesized that a combination of genetic and
      environmental factors prompts an abnormal immune response in patients with
      psoriasis. CD4+ Th cells play a multifaceted role in both immune defense and
      pathogenesis of certain diseases such as psoriasis. Nonetheless, the exact
      contribution of different subpopulations of Th cells in psoriasis is still not
      clear. OBJECTIVE: The aim of present study was to determine the mRNA expression
      level of RORC as potential inducer of Th17 cell differentiation and expression
      pattern of Th17-signature cytokines (IL-17A and IL-22). METHODS: Twenty patients
      with psoriasis and twenty-one healthy subjects were included in the study.
      Peripheral blood mononuclear cells (PBMCs) were separated and expression of three
      genes were determined by quantitative real-time reverse transcriptase PCR (qRT
      PCR). Plasma levels of IL-17 and IL-22 were also evaluated by ELISA. RESULTS:
      RORC, IL-17A and IL-22 gene expression was significantly higher in patients with
      psoriasis compared with healthy controls (P<0.05). In addition, a marked increase
      in plasma IL-17A and IL-22 levels was observed in patient group compared to
      controls (P<0.001). STUDY LIMITATIONS: small number of patients. CONCLUSION:
      These data suggest that Th17 response may contribute to the pathogenesis of
      psoriasis.

PMID- 29641702
TI  - Chronic urticaria in a health maintenance organization of Buenos Aires, Argentina
      - new data that increase global knowledge of this disease.
AB  - BACKGROUND: In spite of the frequency of chronic urticaria, there are no
      epidemiological studies on its prevalence in Argentina. OBJECTIVE: The objective
      of this study was to define the prevalence and epidemiological characteristics of
      chronic urticaria patients in Buenos Aires. METHODS: The population studied were
      the members of the Italian Hospital Medical Care Program, a prepaid health
      maintenance organization located in the urban areas around the Autonomous City of
      Buenos Aires, Argentina. All patients with diagnosis of chronic urticaria members
      of the Italian Hospital Medical Care Program, and with at least 12 months of
      follow up were included in the study. All medical records obtained between
      January 1st, 2012 and December 31, 2014 were analyzed. The prevalence ratio for
      chronic urticaria per 100,000 population with 95% CI for December 31, 2014 was
      calculated. The prevalence rate for the entire population and then discriminated
      for adults and pediatric patients (less than 18 years old at diagnosis) was
      assessed. RESULTS: 158,926 members were analyzed. A total of 463 cases of chronic
      urticaria were identified on prevalence date (68 in pediatrics, 395 in adults),
      yielding a crude point prevalence ratio of 0.29% (CI 95% 0.26-0.31%). The
      observed prevalence of chronic urticaria in the adult population was 0.34 % (95%
      CI 0.31-0.38%), while in pediatrics it was 0.15 % (95% CI 0.11-0.20%). STUDY
      LIMITATIONS: the main weakness is that the results were obtained from an HMO and
      therefore the possibility of selection bias. CONCLUSIONS: chronic urticaria is a
      global condition. Its prevalence in Buenos Aires is comparable with other
      countries.

PMID- 29641703
TI  - Orofacial granulomatosis and diet therapy: a review of the literature and two
      clinical cases.
AB  - Orofacial granulomatosis is a nonspecific term that contains a wide variety of
      granulomatous entities, which share a clinical and histopathological
      presentation. It manifests as persistent or recurrent orofacial swelling, amongst
      other findings. Idiopathic orofacial granulomatosis, characterized by an absence
      of systemic granulomatous disease, is a diagnosis of exclusion. The main
      differential diagnosis is Crohn's disease. Its pathogenesis is unknown, however,
      it seems to be immune-mediated. Patch-test sensitivity to multiple allergens is
      well documented. Currently, therapeutic options consider restrictive diets,
      topical, intralesional, and systemic agents. First-line therapy is currently a
      matter of debate. We present a review of the value of diet therapy in this
      syndrome, along with two illustrative cases.

PMID- 29641705
TI  - Pigmented squamous cell carcinoma: case report and importance of differential
      diagnosis.
AB  - A few cases of pigmented squamous cell carcinoma affecting the skin and the
      ocular and oral mucosa of the elderly have been described in the literature. The
      disease manifests itself as papular and nodular erythematous or pigmented
      lesions. The main clinical differential diagnoses are pigmented basal cell
      carcinoma and melanoma. Histopathological examination is characterized by
      proliferation of atypical squamous cells with formation of horn pearls permeated
      by dendritic melanocytes. For this reason, a careful diagnosis is necessary to
      rule out other tumors that show melanin pigment. Surgical removal is the
      indicated treatment and the prognosis is similar to the classical squamous cell
      carcinoma. We report a case of pigmented squamous cell carcinoma with diagnosis
      confirmed by histological and immunohistochemical examinations.

PMID- 29641704
TI  - Erythromelalgia: a cutaneous manifestation of neuropathy?
AB  - The low prevalence of erythromelalgia, classified as an orphan disease, poses
      diagnostic and therapeutic difficulties. The aim of this review is to be an
      update of the specialized bibliography. Erythromelalgia is an infrequent episodic
      acrosyndrome affecting mainly both lower limbs symmetrically with the classic
      triad of erythema, warmth and burning pain. Primary erythromelalgia is an
      autosomal dominant inherited disorder, while secondary is associated with
      myeloproliferative diseases, among others. In its etiopathogenesis, there are
      neural and vascular abnormalities that can be combined. The diagnosis is based on
      exhaustive clinical history and physical examination. Complications are due to
      changes in the skin barrier function, ischemia and compromise of cutaneous
      nerves. Because of the complexity of its pathogenesis, erythromelalgia should
      always be included in the differential diagnosis of conditions that cause chronic
      pain and/or peripheral edema. The prevention of crisis is based on a strict
      control of triggers and promotion of preventive measures. Since there is no
      specific and effective treatment, control should focus on the underlying disease.
      However, there are numerous topical and systemic therapies that patients can
      benefit from.

PMID- 29641706
TI  - Demographics and spatial distribution of the Brazilian dermatologists.
AB  - The medical-dermatological demographics favors health planning and guides
      expansion of the specialty. We conducted an ecological study of dermatologists
      members of the Brazilian Society of Dermatology (SBD). We evaluated: gender, age,
      address; which were compared with population and human development index
      indicators of municipalities. We evaluated 8384 members, distributed in 527
      (9.5%) municipalities throughout Brazil. The female sex represented 78.4% of the
      members and the median age was 43 (36-54) years. The median density of
      dermatologists was 0.35 (0.21-0.37) per 10,000 inhabitants. The correlation
      (Spearman's rho) between density of dermatologists and human development index
      was 0.39 (p <0.01). The Brazilian dermatologist is characterized as: female, age
      <50 years and presenting an heterogeneous distribution throught the country.

PMID- 29641707
TI  - New and developing therapies for atopic dermatitis.
AB  - Atopic dermatitis is a common inflammatory skin disease. New understanding in
      disease pathogenesis has led to a considerable number of promising new drugs in
      development. New topical agents can be especially helpful for children, providing
      an alternative to the need for chronic topical corticosteroid use. While many
      patients with mild or moderate disease can be managed with topical treatments,
      there are unmet needs for recalcitrant and severe cases. New and developing
      therapies hold promise for real advances in management of this complex disease.

PMID- 29641708
TI  - Lichen simplex chronicus on the scalp: exuberant clinical, dermoscopic, and
      histopathological findings.
AB  - Lichen simplex chronicus is a skin disease that mostly affects female patients,
      with a peak incidence between ages 35 and 50 years. On the scalp, it appears as a
      single or multiple oval lesions, showing scaling and hair shaft loss or breakage.
      An important dermoscopic feature of the disease are the "broom fibers."
      Histopathology reveals the "hamburger" and the "gear wheel" signs. The aim of
      this report is to demonstrate a case of lichen simplex chronicus on the scalp
      with typical and exuberant clinical, dermoscopic, and histopathological findings.

PMID- 29641709
TI  - Atrophic nodular cutaneous amyloidosis.
AB  - Primary cutaneous amyloidosis is limited to the skin without involving any other
      tissue. Nodular amyloidosis is rare, and atrophic nodular cutaneous amyloidosis
      is even rarer. We describe the fourth case of atrophic nodular cutaneous
      amyloidosis by searching PubMed databases. A 52-year-old female presented to our
      hospital with a 2-year history of orange papules and nodules without subjective
      symptom on her right abdomen. Review of systems was negative. Atrophic nodular
      amyloidosis may progress to primary systemic disease in up to 7% of cases.
      Because our patient had no systemic involvement, she was diagnosed with atrophic
      nodular cutaneous amyloidosis based on characteristic symptoms and
      histopathologic examination. Routine follow-up for this patient is necessary to
      detect any potential disease progression.

PMID- 29641710
TI  - Periungual basal cell carcinoma.
AB  - Periungual basal cell carcinoma is rare and needs to be differentiated from other
      common diseases that affect this region. Several factors are associated with the
      development of this tumor, and sun damage seems to play an important role in its
      pathogenesis. Dermoscopy of clinically indolent lesions on the nail unit can
      shorten the diagnostic process and avoid destructive treatment and functional
      damage.

PMID- 29641711
TI  - Subcorneal pustular dermatosis in the pediatric age.
AB  - Subcorneal pustular dermatosis is a rare pustular eruption which occurs mainly in
      middle-aged women and rarely during childhood. We report a case of a 15-year-old
      female with a 4-year history of pustular lesions on the proximal region of the
      upper limbs with subsequent impairment of the trunk. Physical examination
      revealed small pustules distributed on the trunk and proximal region of the
      limbs. Histopathology showed a subcorneal pustule and direct immunofluorescence
      for IgA, IgM, IgG and fibrinogen was negative, confirming the diagnosis of
      subcorneal pustular dermatosis. The patient was treated with dapsone with good
      clinical response after one month. Subcorneal pustular dermatosis is a rare
      condition and there are only isolated cases reported in the literature in
      pediatric patients. Thus, we discuss the main clinical aspects and treatment
      response of this condition during childhood.

PMID- 29641712
TI  - Panniculitis associated with amyopathic dermatomyositis.
AB  - Panniculitis is a rare clinical finding in dermatomyositis, with less than 30
      cases reported and there is only one case associated with the amyopathic subtype
      described in the literature. The present report describes a 49-year-old female
      patient that one year after being diagnosed with amyopathic dermatomyositis,
      presented indurated, painful, erythematous to violaceous nodules located on the
      upper limbs, thighs and gluteal region. Skin biopsy revealed lobular panniculitis
      with a lymphocytic infiltrate. The patient was treated with prednisone and
      methotrexate, but remained unresponsive to treatment.

PMID- 29641713
TI  - Leprosy and American cutaneous leishmaniasis coinfection.
AB  - Brazil is a country with a high prevalence of infectious diseases such as leprosy
      and leishmaniasis. However, coinfection of these diseases is still poorly
      understood. We report a case of a patient who presented with lepromatous leprosy
      and cutaneous-mucosal leishmaniasis at the same period. After clinical,
      laboratory, and histopathological diagnosis, the treatment was introduced and the
      patient showed important clinical improvement. He was followed in our outpatient
      clinic. Both pathologies play an important role in the immune system. Depending
      on the immune response profile of the host, diseases may present themselves in
      different ways. In this case, the patient showed a divergent immune response for
      each disease. We hypothesized that this response is specific for each pathogen.

PMID- 29641714
TI  - Unusual size, topography, and surgical resolution of an acquired fibrokeratoma.
AB  - Acquired fibrokeratoma is a rare benign skin tumor that usually manifests as a
      slow-growing solitary nodular lesion of the digits. We report a case of plantar
      acquired fibrokeratoma evidencing its atypical size and topography, in addition
      to the treatment with simple surgical excision followed by healing by second
      intention. Nondigital fibrokeratomas may occur in 18% of cases and rarely affect
      the palmoplantar region. These lesions are usually asymptomatic and show >= 3cm
      in size at the time of diagnosis due to delayed diagnosis. Complete surgical
      excision is the treatment of choice, which is usually curative. In general,
      primary closure is chosen; however healing by second intention becomes an option
      in regions of difficult approach.

PMID- 29641715
TI  - Corymbiform syphilis associated with three other sexually transmitted infections.
AB  - Secondary syphilis can have different clinical presentations, with corymbiform
      rash as its rarest manifestation. The disease is characterized by a central
      papule surrounded by smaller ones. We report the case of a man who has sex with
      man with corymbiform syphilis. The patient was subsequently diagnosed with HIV
      infection, hepatitis B, non-gonococcal urethritis, as well as infection of the
      central nervous system by treponema. This case not only illustrates a rare
      presentation of secondary syphilis, but also demonstrates the importance of
      further investigation of sexually transmitted infections, particularly among at
      risk patients.

PMID- 29641716
TI  - Bullous pyoderma gangrenosum as a predictor of hematological malignancies.
AB  - Pyoderma gangrenosum may precede, coexist or follow diverse systemic diseases.
      The bullous variety is usually associated with hematologic disorders. From 31
      patients with pyoderma gangrenosum diagnosed in our hospital during 10 years,
      only 2 presented with the bullous type. One patient had previous diagnosis of
      chronic myeloid leukemia. Both had fast-progressive, painful lesions, and both
      showed an excellent response to systemic corticosteroids. In less than 3 months
      the lesions recurred simultaneously with the progression of chronic myeloid
      leukemia in one patient and with the initial diagnosis of acute myeloid leukemia
      in the other one. They died in less than four weeks. These findings emphasize the
      importance of its timely diagnosis. Cutaneous lesions could be the first
      predictor of an underlying disease.

PMID- 29641717
TI  - Do you know this syndrome? Ichthyosis associated with neurological condition and
      alteration of hairs.
AB  - Trichothiodystrophy refers to a heterogeneous group of rare genetic diseases that
      affects neuroectodermal-derived tissues with multisystem involvement. The
      hallmark of these syndromes is the deficiency of sulfur in hair matrix proteins,
      leading to short and brittle hair. Few cases of this rare disorder have been
      published. The authors report a case of trichothiodystrophy in a male infant with
      ichthyosis, photosensitivity, spastic paraparesis, short stature, and neurologic
      and psychomotor retardation. Diagnosis was based on clinical and microscopic
      features of hair samples.

PMID- 29641718
TI  - Dermoscopy in the diagnosis of juvenile xanthogranuloma.
AB  - Juvenile xanthogranuloma is the most common form of non-Langerhans cell
      histiocytosis. It manifests clinically as a red-yellow papule, usually showing
      spontaneous remission. The diagnosis is based on clinical and histological
      findings. We report the use of dermoscopy ("setting sun" pattern) as an adjuvant
      tool in the diagnosis of juvenile xanthogranuloma in a female patient presenting
      with a 2-month history of a pre-auricular papule.

PMID- 29641720
TI  - Case for diagnosis. Atypical genital lesion.
AB  - We present a case of a penile lesion with a clinical appearance similar to Mondor
      penile disease (thrombosis of the dorsal vein of the penis) or penile sclerosing
      lymphangitis. Laboratory evaluation, however, showed a solid lesion, with no
      vascular component to Doppler ultrasonography and no treponema to
      immunohistochemistry. Histological and serological tests were compatible with
      secondary syphilis. The authors reinforce the need for the inclusion of syphilis
      in the differential diagnosis of penile cord injuries.

PMID- 29641719
TI  - Figurate erythematous lesion by Microsporum canis in immunosuppressed patient.
AB  - Dermatophytes are fungi capable of invading keratinized tissues. Isolation of the
      fungus with the culture is essential to guide the treatment, because there are
      more resistant species like Microsporum canis. The chronic use of corticosteroids
      leads to the deregulation of immunity, promoting atypical manifestations of
      infections. Topical antifungal therapy is often insufficient, requiring systemic
      medications. We describe the case of a patient undergoing systemic corticosteroid
      therapy with a large figurate lesion who presented complete response to
      exclusively topical treatment.

PMID- 29641721
TI  - Polyhexanide 0.2% in treatment of trophic foot ulcers in leprosy - preliminary
      study.
AB  - Leprosy is a chronic infectious disease caused by Mycobacterium leprae, which
      affects peripheral nerves, skin and mucous membranes. The impairment of neural
      function as well as sensory or sensory-motor disabilities in leprosy continue to
      be a problem that requires careful attention in the management of patients with
      the aim to avoid or minimize their progression to prevent sequelae. One of the
      most common characteristics of these ulcers is the tendency to chronicity, with
      variable therapeutic response. In this article, we shall discuss the therapeutic
      management of thirteen trophic leprosy ulcers in eight patients using
      polyhexanide 0.2% products.

PMID- 29641722
TI  - Genetic ancestry of patients with porphyria cutanea tarda in a country with mixed
      races: a cross-sectional study (Rio de Janeiro - Brazil).
AB  - Porphyria cutanea tarda has a complex etiology with genetic factors not
      completely elucidated. The miscegenation of the Brazilian population has
      important implications in the predisposition to diseases. There are no studies
      concerning the genetic ancestry of patients with porphyria cutanea tarda from a
      mixed population. Thirty patients living in Rio de Janeiro with sporadic
      porphyria cutanea tarda were studied for the genetic ancestry through informative
      markers - INDELS. There was a significant predominance of European ancestry
      across the sample of patients with porphyria cutanea tarda (70.2%), and a small
      contribution of African and Amerindian ancestry, 20.1% and 10.9%, respectively.

PMID- 29641723
TI  - Evaluation of nickel and cobalt release from mobile phone devices used in Brazil.
AB  - Nickel and cobalt are often responsible for metal-induced allergic contact
      dermatitis. With the increasing use of cell phones, we observed an increase in
      cases reports on telephone-related allergic contact dermatitis. The present study
      evaluated nickel and cobalt release from mobile phones used in Brazil. We
      evaluated devices of 6 brands and 20 different models using nickel and cobalt
      allergy spot tests. Of the 20 models, 64.7% tested positive for nickel, with
      41.1% positive results for the charger input and 23.5% for other tested areas.
      None of them was positive for cobalt. Nickel release was more common in older
      models.

PMID- 29641724
TI  - Undifferentiated pleomorphic sarcoma.

PMID- 29641725
TI  - Methotrexate-induced mucositis with extra-mucosal involvement after acidental
      overdose.

PMID- 29641726
TI  - Urban American cutaneous leishmaniasis.

PMID- 29641727
TI  - Topical corticosteroid therapy: a treatment option for nevus lipomatosus
      cutaneous superficialis?

PMID- 29641728
TI  - Giant onychomatricoma.

PMID- 29641729
TI  - Fox-Fordyce disease.

PMID- 29641730
TI  - Preoperatively undiagnosed papillary thyroid carcinoma in patients
      thyroidectomized for benign multinodular goiter.
AB  - OBJECTIVE: Incidental thyroid cancers (ITCs) are often microcarcinomas; among
      them, the most frequent histotype is the papillary one. The purpose of this study
      was to evaluate the rate of papillary thyroid cancer (PTC) in patients
      thyroidectomized for benign multinodular goiter. SUBJECT AND METHODS: We
      retrospectively evaluated the histological incidence of PTC in 207 consecutive
      patients who, in a 1-year period, underwent thyroidectomy for benign multinodular
      goiter. All patients came from an iodine-deficient area (Orleans, France) with
      three nuclear power stations located in the neighboring areas of the county town.
      RESULTS: Overall, 25 thyroids (12.1%) harbored 37 PTC, of which 31 were
      microcarcinomas. In these 25 PTC patients, mean age was 55 +/- 10 years (range 30
      75), female:male ratio 20:5 (4:1). In 10 patients (40% of 25 and 4.8% of 207),
      PTCs were bilateral, and in 7 (2 with microPTCs) the thyroid capsule was
      infiltrated. These 7 patients underwent central and lateral cervical lymph node
      dissections, which revealed lymph node metastases in one and two cases,
      respectively. Radioiodine treatment was performed in 7 cases. Neither mortality
      nor transient and permanent nerve injuries were observed. Four (16%) transient
      hypocalcaemias occurred as early complications. At last follow-up visit (mean
      length of follow-up 17.2 +/- 3.4 months), all patients were doing well and free
      of any clinical local recurrence or distant metastases. CONCLUSION: With a 12%
      risk that multinodular goiter harbors preoperatively unsuspected PTCs, which can
      have already infiltrated the capsule and that can be accompanied by PTC foci
      contralaterally, an adequate surgical approach has to be considered.

PMID- 29641731
TI  - Reliability of Thyroid Imaging Reporting and Data System (TI-RADS), and
      ultrasonographic classification of the American Thyroid Association (ATA) in
      differentiating benign from malignant thyroid nodules.
AB  - OBJECTIVE: Ultrasonography (US) is the best diagnostic tool for initial
      assessment of thyroid nodule. Recently, data reporting systems for thyroid
      lesions, such as the Thyroid Imaging Reporting and Data System (TI-RADS) and
      American Thyroid Association (ATA), which stratifies the risk for malignancy,
      have demonstrated good performance in differentiating malignant thyroid nodules.
      The purpose of this study is to determine the reliability of both data reporting
      systems in predicting thyroid malignancy in a tertiary care hospital. MATERIALS
      AND METHODS: We evaluated 195 thyroid nodules using modified TI-RADS and ATA risk
      stratification. The results were compared to the cyto-pathology analysis.
      Histopathological results were available for 45 cases after surgery, which is
      considered the golden standard for diagnosis of thyroid cancer. RESULTS: When
      compared with cytological results, sensitivity, specificity, negative predictive
      value (NPV), and accuracy were 100, 61.1, 100, and 63%, respectively, for TI
      RADS; and 100, 75, 100, and 76%, respectively, for ATA. When compared with
      histopathological results, sensitivity, specificity, NPV, and accuracy were 90,
      51.4, 94.7, and 60% respectively, for TI-RADS; and 100, 60, 100, and 68%,
      respectively, for ATA. All patients with malignant nodules were classified in the
      categories 4 or 5 of TI-RADS and in the intermediate or high suspicion risk
      according to the ATA system. CONCLUSION: Both TI-RADS and the ATA guidelines have
      high sensitivity and NPV for the diagnosis of thyroid carcinoma. These systems
      are feasible for clinical application, allowing to better select patients to
      undergo fine-needle aspiration biopsies.

PMID- 29641732
TI  - Dynamic changes of central thyroid functions in the management of Cushing's
      syndrome.
AB  - OBJECTIVE: The aim of this study was to determine the frequency of central
      thyroid dysfunctions in Cushing's syndrome (CS). We also aimed to evaluate the
      frequency of hyperthyroidism due to the syndrome of the inappropriate secretion
      of TSH (SITSH), which was recently defined in patients with insufficient
      hydrocortisone replacement after surgery. MATERIALS AND METHODS: We evaluated
      thyroid functions (TSH and free thyroxine [fT4]) at the time of diagnosis, during
      the hypothalamo-pituitary-adrenal axis recovery, and after surgery in 35 patients
      with CS. The patients were separated into two groups: ACTH-dependent CS (group 1,
      n = 20) and ACTH-independent CS (group 2, n = 15). Patients' clinical and
      laboratory findings were evaluated in five visits in the outpatient clinic of the
      endocrinology department. RESULTS: The frequency of baseline suppressed TSH
      levels and central hypothyroidism were determined to be 37% (n = 13) and 26% (n =
      9), respectively. A negative correlation was found between baseline cortisol and
      TSH levels (r = -0.45, p = 0.006). All patients with central hypothyroidism and
      suppressed TSH levels showed recovery at the first visit without levothyroxine
      treatment. SITSH was not detected in any of the patients during the postoperative
      period. No correlation was found between prednisolone replacement after surgery
      and TSH or fT4 levels on each visit. CONCLUSION: Suppressed TSH levels and
      central hypothyroidism may be detected in CS, independent of etiology. SITSH was
      not detected in the early postoperative period due to our adequate prednisolone
      replacement doses.

PMID- 29641734
TI  - The effect of metabolic surgery on type 1 diabetes: meta-analysis.
AB  - OBJECTIVE: Metabolic and bariatric surgery has a definite role in the management
      of obese patients with type 2 diabetes mellitus (T2DM). There is also evidence of
      such surgery improving the health of type 1 diabetic (T1DM) patients. The aim of
      this paper is to explore the effect of metabolic and bariatric surgery on T1DM.
      MATERIALS AND METHODS: A comprehensive search of PubMed and Google Scholar was
      performed to identify relevant papers reporting metabolic and bariatric surgery
      effects on T1DM. A statistical analysis is applied after data synthesis. A forest
      plot and Pearson correlation are then calculated. RESULTS: Of the 567 papers that
      were identified, 558 articles did not fulfill the inclusion criteria and were
      therefore excluded. Nine studies involving 78 patients were selected for this
      metaanalysis. There was improvement in HBA1c (p value = 0.40), insulin dose (p
      value = 0.0001) and BMI (p value = 0.00001) after surgery. However, improvement
      in the HBA1c did not reach statistical significance. There was a weak correlation
      between postoperative insulin dose and BMI change after surgery (r = -0.177).
      There was a negligible correlation between HBA1c and BMI change after operations
      (r = -0.01). CONCLUSION: Current metabolic/bariatric surgery is improving T1DM in
      obese and morbidly obese patients. This is not exclusively related to excess
      weight loss (EWL) as previously thought. Therefore, there is a role for other
      factors, which are potential players to reproduce the same effect in nonobese
      T1DM patients.

PMID- 29641733
TI  - Impact of historic histopathologic sample review on the risk of recurrence in
      patients with differentiated thyroid cancer.
AB  - OBJECTIVE: To compare the historic risk of recurrence (RR) and response to
      therapy to risk stratification estimated with historical pathology reports (HPRs)
      and contemporary re-review of the pathological slides in patients with
      differentiated thyroid cancer (DTC). SUBJECTS AND METHODS: Out of 210 DTC
      patients with low and intermediate RR who underwent total thyroidectomy and
      remnant ablation in our hospital, 63 available historic pathologic samples (HPS)
      were reviewed. The RR and the response to therapy were evaluated considering
      historical histological features (histological type, tumor size, capsular
      invasion, number of lymph node metastases) and then, reassessed after observing
      additional histological features (vascular invasion, extrathyroidal extension,
      size of lymph node metastases, presence of extranodal extension, and/or status of
      the resection margins). RESULTS: A change in the RR category was observed in 16
      of 63 cases (25.4%). Out of 46 patients initially classified as low RR, 2
      patients were reclassified as intermediate RR, 4 as high RR, and 1 as noninvasive
      follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Out of
      17 patients initially classified as intermediate RR, 3 were reassigned to the low
      RR group, 5 as high RR, and 1 as NIFTP. The percentages of structural incomplete
      response at final follow-up changed from 2.2 to 0% (p = 1) in patients with low
      RR and from 6.3 to 20% (p = 0.53) in patients with intermediate RR. CONCLUSION: A
      detailed report of specific features in the HPR of patients with DTC might give a
      more accurate RR classification and a better estimation of the response to
      treatment.

PMID- 29641735
TI  - Progranulin concentration in relation to bone mineral density among obese
      individuals.
AB  - OBJECTIVE: Adipose tissue, particularly visceral adipose tissue, secretes a
      variety of cytokines, among which progranulin is a glycoprotein related to the
      immune system. Along with other secreted proteins, progranulin may be associated
      with bone mineral density. The aim of this study was to find out whether there
      are associations between the progranulin and bone mineral density among obese
      people. SUBJECTS AND METHODS: This cross-sectional study was conducted on 244
      obese participants (aged 22-52). Serum progranulin, high sensitive C-reactive
      protein, oxidised-low dencity lipoprotein, tumor necrosis factor-alpha,
      parathormone, vitamin D, and interleukins of 1 beta, 4, 6, 10, 13, and 17
      concentrations were measured. Anthropometric measurements, body composition and
      bone mineral density were also assessed. RESULTS: Serum progranulin was directly
      associated with interleukin-6 and interleukin-1beta, while it had a negative
      association with interleukin-17 and tumor necrosis factor-alpha. We also observed
      a statistically significant direct association between progranulin concentration
      and visceral fat, abdominal fat, waist, abdominal and hip circumferences, hip T
      score, and Z-score and T-score for the lumbar region. A partial correlation test
      has also shown a significant positive correlation regarding serum progranulin and
      the hip Z-score. Moreover, progranulin level is inversely associated with
      ospteopenia (P = 0.04 and CI: 0.17,0.96). CONCLUSION: Our study revealed that
      central obesity may be related to increased progranulin concentration. In
      addition, progranulin concentration was directly related to bone formation
      parameters, which indicates the protective effects of progranulin on bone
      density. Further studies are needed to clarify the exact mechanisms underlying
      these associations.

PMID- 29641736
TI  - Impact of self-reported fasting duration on lipid profile variability,
      cardiovascular risk stratification and metabolic syndrome diagnosis.
AB  - OBJECTIVE: We sought to investigate the impact of self-reported fasting duration
      times on the lipid profile results and its impact on the cardiovascular risk
      stratification and metabolic syndrome diagnosis. SUBJECTS AND METHODS: We
      analyzed data from all consecutive individuals evaluated in a comprehensive
      health examination at the Hospital Israelita Albert Einstein from January to
      December 2015. We divided these patients in three groups, according to the
      fasting duration recalled (< 8h, 8-12h and > 12h). We calculated the global
      cardiovascular risk and diagnosed metabolic syndrome according to the current
      criteria and estimated their change according to fasting duration. RESULTS: A
      total of 12,196 (42.3 +/- 9.2 years-old, 30.2% females) patients were evaluated.
      The distribution of cardiovascular risk was not different among groups defined by
      fasting duration in both men and women (p = 0.547 for women and p = 0.329 for
      men). Similarly, the prevalence of metabolic syndrome was not influenced by the
      fasting duration (p = 0.431 for women and p = 0.166 for men). CONCLUSION: Self
      reported fasting duration had no significant impact on the lipid profile results,
      including triglyceride levels. Consequently, no changes on the cardiovascular
      risk stratification using the Framingham risk score nor changes on the prevalence
      of metabolic syndrome were noted.

PMID- 29641737
TI  - Effect of one time high dose "stoss therapy" of vitamin D on glucose homeostasis
      in high risk obese adolescents.
AB  - OBJECTIVE: To study the effect of using a one time high dose "stoss therapy" of
      vitamin D2 (ergocalciferol: VD2) on indices of insulin sensitivity {whole body
      sensitivity index: WBISI} and secretion {insulinogenic index: IGI} measured
      during an oral glucose tolerance test (OGTT) in obese adolescents with VDD (25
      OHD; serum metabolite of vit D: < 30 ng/dL). SUBJECTS AND METHODS: In a
      randomized placebo controlled cross over design 20 obese adolescents with vitamin
      D deficiency (VDD) had baseline OGTT. Arm A received one time high dose 300,000
      IU of ergocalciferol and Arm B received placebo. After 6 weeks the adolescents
      were reassigned to Arm A if they were in Arm B and vice versa. 25OHD, calcium,
      parathyroid hormone, comprehensive metabolic panel, urine calcium creatinine
      ratio were measured at each study visit. OGTTs to assess indices of sensitivity
      and secretion were done at baseline, 6 weeks and 12 weeks respectively. RESULTS:
      Adolescents were obese and insulin resistant (mean +/- SD: mean age = 15.1 +/-
      1.9 years; BMI: 32.7 +/- 9.8; homeostatic model of insulin resistance: HOMA-IR:
      4.2 +/- 2.8). Stoss therapy with VD2 increased 25OHD from baseline (16.7 +/- 2.9
      to 19.5 +/- 4.5; p = 0.0029) when compared to the placebo. WBISI (2.8 +/- 1.9)
      showed a trend towards improvement in Rx group (p = 0.0577) after adjustment for
      covariates. IGI (3 +/- 2.2) showed an improvement in both Rx and placebo groups.
      CONCLUSIONS: Our study demonstrated that using a high dose of VD2 (300,000 IU)
      did not have any beneficial effect on insulin sensitivity (whole body sensitivity
      index {WBISI}) and secretory indices (insulinogenic index {IGI}) in obese
      adolescents. High dose "stoss therapy" of VD2 did not appear to have any
      beneficial effect on glucose homeostasis on obese adolescents.

PMID- 29641738
TI  - Clinical outcomes of low and intermediate risk differentiated thyroid cancer
      patients treated with 30mCi for ablation or without radioactive iodine therapy.
AB  - OBJECTIVE: To retrospectively evaluate the outcomes of patients with low and
      intermediate risk thyroid carcinoma treated with total thyroidectomy (TT) and who
      did not undergo radioiodine remnant ablation (RRA) and to compare them to
      patients receiving low dose of iodine (30 mCi). SUBJECTS AND METHODS: A total of
      189 differentiated thyroid cancer (DTC) patients treated with TT followed by
      30mCi for RRA or not, followed in two referral centers in Brazil were analyzed.
      RESULTS: From the 189 patients, 68.8% was ATA low-risk, 30.6% intermediate and
      0.6% high risk. Eighty-seven patients underwent RRA and 102 did not. The RRA
      groups tended to be younger and had a higher frequency of extra-thyroidal
      extension (ETE). RRA did not have and impact on response to initial therapy
      neither in low (p = 0.24) nor in intermediate risk patients (p = 0.66). It also
      had no impact on final outcome and most patients had no evidence of disease (NED)
      at final follow-up. Recurrence/persistence of disease was found in 1.2% of RRA
      group and 2% in patients treated only with TT (p = 0.59). CONCLUSIONS: Our study
      shows that in low and intermediate-risk patients, RRA with 30 mCi seems to have
      no major advantage over patients who did not undergo RRA regarding response to
      initial therapy in each risk group and also in long term outcomes.

PMID- 29641739
TI  - Effects of drying and storage conditions on the stability of TSH in blood spots.
AB  - OBJECTIVE: To evaluate the influence of sample drying and storage temperature on
      TSH stability in neonatal screening. SUBJECTS AND METHODS: Blood samples from 29
      adult volunteers as a surrogate for neonatal blood (10 with normal TSH, 9 with
      overt hypothyroid and 10 with subclinical hypothyroidism) were spotted on filter
      paper and dried at 22 degrees C or 35 degrees C for 3 hours. The samples were
      then stored at 22 degrees C, -4 degrees C, or -20 degrees C, and TSH measurements
      were performed at day 0 (D0), D7, D30, D60, D180, and D360 of storage. RESULTS:
      The drying temperature did not interfere with TSH measurement on D0. TSH values
      remained stable up to D30 when stored at 22 degrees C and were stable up to D60
      when stored in a refrigerator or freezer. Samples stored at 22 degrees C had a
      greater decrease in TSH values than samples stored in a refrigerator or a
      freezer. CONCLUSIONS: Freezer storage is not advantageous compared to storage in
      the refrigerator. At the end of one year, if confirmation of the initial result
      is required, a reduction of TSH concentrations should be taken into account.

PMID- 29641740
TI  - Diagnostic utility of DREAM gene mRNA levels in thyroid tumours.
AB  - OBJECTIVE: The transcriptional repressor DREAM is involved in thyroid-specific
      gene expression, thyroid enlargement and nodular development, but its clinical
      utility is still uncertain. In this study we aimed to investigate whether DREAM
      mRNA levels differ in different thyroid tumors and how this possible difference
      would allow the use of DREAM gene expression as molecular marker for diagnostic
      and/or prognosis purpose. MATERIALS AND METHODS: We quantified DREAM gene mRNA
      levels and investigated its mutational status, relating its expression and
      genetic changes to diagnostic and prognostic features of 200 thyroid tumors,
      being 101 malignant [99 papillary thyroid carcinomas (PTC) and 2 anaplastic
      thyroid carcinomas] and 99 benign thyroid lesions [49 goiter and 50 follicular
      adenomas (FA)]. RESULTS: Levels of mRNA of DREAM gene were higher in benign
      (0.7909 +/- 0.6274 AU) than in malignant (0.3373 +/- 0.6274 AU) thyroid lesions
      (p < 0.0001). DREAM gene expression was able to identify malignancy with 66.7%
      sensitivity, 85.4% specificity, 84.2% positive predictive value (PPV), 68.7%
      negative predictive value (NPV), and 75.3% accuracy. DREAM mRNA levels were also
      useful distinguishing the follicular lesions FA and FVPTC with 70.2% sensitivity,
      73.5% specificity, 78.5% PPV, 64.1% NPV, and 71.6% accuracy. However, DREAM gene
      expression was neither associated with clinical features of tumor aggressiveness,
      nor with recurrence or survival. Six different genetic changes in non-coding
      regions of DREAM gene were also found, not related to DREAM gene expression or
      tumor features. CONCLUSION: We suggest that DREAM gene expression may help
      diagnose thyroid nodules, identifying malignancy and characterizing follicular
      patterned thyroid lesions; however, it is not useful as a prognostic marker.

PMID- 29641742
TI  - Study of contacts of individuals diagnosed with sexually transmitted infections
      in the correctional setting.

PMID- 29641741
TI  - Short-term insulin intensive therapy decreases MCP-1 and NF-kappaB expression of
      peripheral blood monocyte and the serum MCP-1 concentration in newlydiagnosed
      type 2 diabetics.
AB  - OBJECTIVE: To observe the effect of short-term insulin intensive treatment on the
      monocyte chemoattractant protein-1 (MCP-1) as well as on the nuclear factor-kappa
      B (NF-kappaB) expression of peripheral blood monocyte. This is also in addition
      to observing the serum MCP-1 level in newlydiagnosed type 2 diabetic patients and
      probing its anti-inflammation effects. SUBJECTS AND METHODS: Twenty newly
      diagnosed type 2 diabetic patients were treated with an insulin intensive
      treatment for 2 weeks. MCP-1 and NF-kappaB expression on the monocyte surface
      were measured with flow cytometry, the serum MCP-1 level was measured by enzyme
      linked immunosorbent assay (ELISA) during pretreatment and post-treatment.
      RESULTS: After 2 weeks of the treatment, MCP-1 and NF-kappaB protein expression
      of peripheral blood monocyte and serum MCP-1 levels decreased significantly
      compared with those of pre-treatment, which were (0.50 +/- 0.18)% vs (0.89 +/-
      0.26)% (12.22 +/- 2.80)% vs (15.53 +/- 2.49)% and (44.53 +/- 3.97) pg/mL vs
      (49.53 +/- 3.47) pg/mL, respectively (P < 0.01). The MCP-1 expression on monocyte
      surface had a significant positive relationship with serum MCP-1 levels (r =
      0.47, P < 0.01). CONCLUSIONS: Short-term insulin intensive therapy plays a role
      in alleviating the increased inflammation reaction in type 2 diabetics.

PMID- 29641743
TI  - Prevalence and associated risk factors of latent tuberculosis infection in a
      Spanish prison.
AB  - Aim: To determine the prevalence of latent tuberculosis infection (LTI) in a
      Spanish prison, analyze the main sociodemographic and clinical variables
      associated with this condition and estimate the percentage of individuals with
      LTI who have received chemoprophylactic treatment. Materials and methods: Cross
      sectional study including inmates hosted in the Madrid VI Prison on 16/07/2016.
      Exclusion criteria: history of tuberculosis; non-updated tuberculin test
      according to the Tuberculosis Prevention and Control Program in Prisons protocol.
      Information of the variables was collected from SANIT and SIP programs, and by
      checking the clinical records of inmates. Description of the participant
      population and comparison between the frequency of distribution of the
      independent variables in LTI present and absent groups were performed, the last
      calculating the p value with Ji2 and Mann-Whitney U tests. Bivariate and
      multivariate analysis have been carried out with a logistic regression model.
      Results: 936 individuals have been included. The prevalence of LTI in prison is
      54.6%. This condition has been linked to the sociodemographic variables age, sex
      and nationality of origin, being age the one that has shown the strongest
      association. Among the other factors analyzed, only HCV infection behaves as a
      predictor of LTI. 30.3% of the individuals with LTI have completed or are
      receiving chemoprophylactic treatment in the moment of the study. Discussion: LTI
      prevalence is high in the Spanish current prison population. The results of the
      study emphasize the relevance of the LTI screening in the prison setting,
      specially among high risk groups, and point out the need of a greater effort in
      the indication and completion of the chemoprophylactic treatment.

PMID- 29641744
TI  - Risk factors associated with drug use before imprisonment in Peru.
AB  - Objective: To assess the prevalence of drug abuse before prison admission and to
      identify associated sociodemographic and family history risk factors, according
      to gender, in prisons of Peru. Materials and methods: A secondary analysis was
      carried out with data from the First National Prisoner Census 2016, using a
      questionnaire of 173 items that was applied to the whole prison population of
      Peru. The types of drugs used before admission were analyzed according to
      characteristics of the penitentiary population, and generalized linear models
      were used to calculate prevalence ratios with 95% confidence intervals to
      identify possible factors associated with drug use. Results: Out of a population
      of 76,180 prisoners, 71,184 (93.4%) answered the survey (men 67,071, 94.2%). The
      overall prevalence of drug consumption before admission was 24.4% (25.3 % in men
      and 9.1% in women), the highest prevalence in the 18-29 age group (36.3% in men
      and 14.9% in women). The most commonly used drugs were marijuana (58.2%), coca
      paste/cocaine or crack (40.3%) and inhalants (1%). The factors most strongly
      associated with consumption were having a family member who consumed drugs
      (59.8%), history of previous imprisonment (59.1%), unemployment (48.4%),
      relationships at school with classmates who had problems with the law (46.9%),
      background of a family member who attended a penitentiary (38.4%), and history of
      running away from home before age 15 (35.9%). Conclusions: In Peru, drug use is
      higher in the prison population than in the general population, and there are
      differences according to sex in the prevalence of drug use and associated factors
      prior to admission to a prison. The study demonstrated that childhood events,
      such as child abuse, having a family member imprisoned, having a family member
      who used drugs, or who previously abused alcohol, are factors associated with
      drug use in the penitentiary population. Some of these risk factors are
      modifiable, so it is important to consider these in the design of social and
      health policies focused on specific subpopulations to prevent drug use and crime.

PMID- 29641745
TI  - Availability and use of healthcare resources in prisons according to the
      transference model: a comparative study in Spain.
AB  - Objective: In most European countries, correctional healthcare provision is under
      strain or in the process of change regarding its management model and the
      implications that such modifications may entail for the improvement of inmates'
      health. This paper compares the functioning and the results of health management
      in a facility whose healthcare service is integrated within an autonomic health
      system and others which depend on the department of corrections. Materials and
      methods: Cross-sectional study where the study unit is the facility itself. From
      the data collected from the record of Monthly Health Statistics of Penitentiary
      Institutions we have constructed a series of indicators according to the
      recommendations of the National Health System. Results: The physician to nurse
      ratio per inmate is higher in the transferred facility. Only the transferred
      establishment has telemedicine resources. Attendance to primary health services
      is higher that in all non-transferred establishments, while the mean attendance
      to specialized consultation in the transferred facility doubles that of the
      remaining centers. Discussion: We have observed greater access to specialized
      care in the correctional facility managed by the community health system when
      compared to that of the facilities managed by Penitentiary Institutions. This
      statement is based on a series of effectivity indicators and results that have
      provided significantly improved outcome in the transferred facility.

PMID- 29641746
TI  - The demonstration.

PMID- 29641747
TI  - Physical activity in prison: should it be a first-line healthcare intervention?

PMID- 29641748
TI  - Physicochemical properties of calcium silicate-based formulations MTA Repair HP
      and MTA Vitalcem.
AB  - OBJECTIVE: This study aimed to analyze the following physicochemical properties:
      radiopacity, final setting time, calcium release, pH change, solubility, water
      sorption, porosity, surface morphology, and apatite-forming ability of two
      calcium silicate-based materials. MATERIAL AND METHODS: We tested MTA Repair HP
      and MTA Vitalcem in comparison with conventional MTA, analyzing radiopacity and
      final setting time. Water absorption, interconnected pores and apparent porosity
      were measured after 24-h immersion in deionized water at 37 degrees C. Calcium
      and pH were tested up to 28 d in deionized water. We analyzed data using two-way
      ANOVA with Student-Newman-Keuls tests (p<0.05). We performed morphological and
      chemical analyses of the material surfaces using ESEM/EDX after 28 d in HBSS.
      RESULTS: MTA Repair HP showed similar radiopacity to that of conventional MTA.
      All materials showed a marked alkalinizing activity within 3 h, which continued
      for 28 d. MTA Repair HP showed the highest calcium release at 28 d (p<0.05). MTA
      Vitalcem showed statistically higher water sorption and solubility values
      (p<0.05). All materials showed the ability to nucleate calcium phosphate on their
      surface after 28 d in HBSS. CONCLUSIONS: MTA Repair HP and MTA Vitalcem had
      extended alkalinizing activity and calcium release that favored calcium phosphate
      nucleation. The presence of the plasticizer in MTA HP might increase its
      solubility and porosity. The radiopacifier calcium tungstate can be used to
      replace bismuth oxide.

PMID- 29641749
TI  - Dynamics of the seasonal airborne propagation of Staphylococcus aureus in
      academic dental clinics.
AB  - OBJECTIVE: Staphylococcus aureus strains can be disseminated during dental
      treatments and occasionally lead to the contamination and infection of patients
      and dentists, which is an important public health problem. The dynamics of the
      airborne propagation and the genetic diversity of S. aureus isolated in an
      academic dental clinic environment were investigated using isoenzyme typing.
      Materials and MethodsThe isoenzymes of 44 previously reported isolates were
      obtained from fresh cultures and extracted using glass beads. Nine isoenzymes
      were investigated using multilocus enzyme electrophoresis (MLEE). The genetic
      diversity and relationship among the strains (electrophoretic type - ET) were
      determined using statistics previously described by Nei25 (1972) and the SAHN
      grouping method (UPGMA algorithm). RESULTS: Clonal pattern analyses indicated a
      high level of genetic polymorphism occurring among the 33 ETs, which were grouped
      into five taxa. Each taxon presented one or more clusters that were moderately
      related and that contained two or more identical/highly related isolates,
      revealing seasonal airborne propagation in these dental clinic environments.
      CONCLUSIONS: These data suggest the occurrence of active microevolutionary
      processes in S. aureus as well as the possibility of environmental propagation
      during a 14-month time span. Such findings are important to show that multiuser
      academic dental clinics can retain certain strains that are spreadable to
      different niches.

PMID- 29641750
TI  - The impact of nonsyndromic cleft lip with or without cleft palate on oral health
      related quality of life.
AB  - : Nonsyndromic cleft lip with or without cleft palate (NSCL+/-P) compromises oral
      health, leading to missing or malformed teeth, and hampering oral hygiene. Apart
      from anatomic damages, NSCL+/-P also culminates in an impact on the routine
      quality of life with social privation and psychological embarrassment. OBJECTIVE:
      To evaluate the impact of NSCL+/-P on oral health-related quality of life.
      MATERIAL AND METHODS: The study was classified as exploratory and descriptive,
      with quantitative approach. Patients with NSCL+/-P treated between August 2013
      and September 2014 at the Cleft Lip and Palate Integral Care Center (CAIF),
      Curitiba, Brazil, were invited to participate. Age and sex-related data were
      collected, as well as level of education, financial income, type of orofacial
      cleft, use of orthodontic and prosthetic appliances, and number of previous
      orofacial surgeries. Selected patients were asked to answer the Oral Impact on
      Daily Performance (OIDP) questionnaire designed to measure the impact of oral
      health on daily performances. RESULTS: The sample was composed of 103 (44.59%)
      women and 128 (55.41%) men, with mean age of 19.74 +/- 10.20 (7-65) years. The
      OIDP values ranged from 1 to 175 in 114 (49.35%) patients (mean: 22.38), whereas
      117 patients (50.65%) presented total OIDP value equal to zero. High negative
      impact of NSCL+/-P on daily performances was detected when associated with the
      female sex (p=0.037). Daily performances related to phonetics (OIDP2; 2.63) and
      aesthetics (OIDP5; 2.48) presented the highest average values when compared to
      other daily performances, except OIDP6. The main symptoms and reported oral
      problems comprised the aesthetic dissatisfaction. CONCLUSIONS: Almost half of the
      patients evaluated in this study showed negative impact of NSCL+/-P in the
      performance of daily activities.

PMID- 29641751
TI  - Association between TNFalpha - 308 G/A polymorphism and oral lichen planus (OLP):
      a meta-analysis.
AB  - OBJECTIVES: To determine whether Tumor Necrosis Factor alpha (TNFalpha) -308 G/A
      polymorphism is associated with oral lichen planus (OLP). MATERIAL AND METHODS: A
      systematic electronic search of the literature was conducted to identify all
      published studies on the association between TNFalpha -308 G/A polymorphism and
      OLP. All case-control studies evaluating the TNFalpha -308 G/A polymorphisms in
      OLP were selected. A meta-analysis of the studies that fulfilled the inclusion
      criteria was performed. Odds ratios (OR) with 95% confidence intervals (CI) were
      also calculated. RESULTS: Seven studies comprising 450 OLP cases and 867 controls
      were included in the meta-analysis. In the pooled analysis, TNFalpha -308 G/A
      polymorphism was associated with OLP with random effects and OR of 2.33
      (95%CI=1.07-5.11; p=0.03), assuming a dominant mode of inheritance (AA+GA vs.
      GG). In the subgroup analysis by ethnicity, TNFalpha -308 G/A was associated with
      a significantly increased odds ratio of OLP in mixed ethnicity (OR=5.22;
      95%CI=1.93-14.15; p=0.001), but not in Asians (OR=1.57; 95%CI=0.54-4.54; p=0.41)
      or Caucasians (OR=1.45; 95%CI=0.19-11.22; p=0.72). For subgroup analysis based on
      HCV (hepatitis C virus) infection status, significant increased risk of OLP was
      found among patients with mixed HCV infection status (OR=3.77; 95%CI=1.07-13.2;
      p=0.038), but not in patients without HCV infection (OR=2.09; 95%CI=0.63-6.91;
      p=0.22) and patients with HCV infection (OR=0.48; 95%CI=0.13-1.69; p=0.25).
      CONCLUSION: Our results suggest that -308 G/A polymorphism in TNFalpha is a
      potential genetic marker for OLP.

PMID- 29641753
TI  - Thinning regimes and initial spacing for Eucalyptus plantations in Brazil.
AB  - This study focuses on the effects of different thinning regimes on clonal
      Eucalyptus plantations growth. Four different trials, planted in 1999 and located
      in Bahia and Espirito Santo States, were used. Aside from thinning, initial
      planting density, and post thinning fertilization application were also
      evaluated. Before canopy closure, and therefore before excessive competition
      between trees took place, it was found that stands planted under low densities
      (667 trees per hectare) presented a lower mortality proportion when compared to
      stand planted under higher densities (1111 trees per hectare). However, diameter
      growth prior to thinning operations was not statistically different between these
      two densities, presenting an overall mean of 4.9 cm/year. After canopy closure
      and the application of the thinning treatments, it was found that thinning
      regimes beginning early in the life of the stand and leaving a low number of
      residual trees presented the highest diameter and height growth. Unthinned
      treatments and thinning regimes late in the life of the stand (after 5.5 years),
      leaving a large number of residual trees presented the highest values of basal
      area production. The choice of the best thinning regime for Eucalyptus clonal
      material will vary according to the plantation objective.

PMID- 29641752
TI  - The effect of periodontal therapy on neopterin and vascular cell adhesion
      molecule-1 levels in chronic periodontitis patients with and without acute
      myocardial infarction: a case-control study.
AB  - : The presence of neopterin in gingival crevicular fluid (GCF) is a marker for
      local and acute immune activation, and the presence of vascular cell adhesion
      molecule (VCAM-1) in GCF is accepted as a marker for chronic vascular
      inflammation. OBJECTIVES: This study aimed to evaluate effects of periodontal
      treatment on GCF levels of neopterin and VCAM-1 in patients with chronic
      periodontitis (CP) with acute myocardial infarction (AMI) compared with
      systemically healthy CP patients. MATERIAL AND METHODS: Sixty subjects (20 CP
      patients with AMI, 20 healthy CP patients, and 20 healthy controls) were
      included. GCF samples were analyzed at baseline and after 3 and 6 months, and the
      probing pocket depth (PD), clinical attachment level (CAL), bleeding on probing,
      gingival (GI) and plaque (PI) indices were recorded. We determined neopterin and
      VCAM-1 levels (concentration and total amount) using enzyme-linked immunosorbent
      assay (ELISA). No significant differences were seen between the AMI+CP and CP
      groups for PI, GI, GCF levels of neopterin and VCAM-1 at baseline. RESULTS: The
      number of teeth with 5 mm<=CAL<7 mm and CAL>=7 mm were significantly increased in
      the AMI+CP group at baseline. There were no significant differences between the
      AMI+CP and CP for PI, CAL, GCF volumes, and the AMI+CP group had the highest
      clinical improvement in the number of teeth with 5 mm<=CAL<7 mm at the sixth
      month. There were significant positive correlations between clinical periodontal
      inflammation and the presence of neopterin and VCAM-1 in GCF prior to and
      following periodontal treatment, and between the GCF volume and clinical
      parameters. CONCLUSIONS: Data suggest that the total amount and concentration of
      neopterin and VCAM-1 in GCF seemed to be closely associated with periodontal
      disease severity in CP patients with AMI. Moreover, the results of our study
      demonstrate that the past periodontal status is potentially correlated between
      groups, with similar periodontal disease severity.

PMID- 29641754
TI  - How to live and do science in a changing world.

PMID- 29641755
TI  - Wall function treatment for bubbly boundary layers at low void fractions.
AB  - The present work investigates the role of different treatments of the lower
      boundary condition on the numerical prediction of bubbly flows. Two different
      wall function formulations are tested against experimental data obtained for
      bubbly boundary layers: (i) a new analytical solution derived through asymptotic
      techniques and (ii) the previous formulation of Troshko and Hassan (IJHMT, 44,
      871-875, 2001a). A modified k-e model is used to close the averaged Navier-Stokes
      equations together with the hypothesis that turbulence can be modelled by a
      linear superposition of bubble and shear induced eddy viscosities. The work
      shows, in particular, how four corrections must the implemented in the standard
      single-phase k-e model to account for the effects of bubbles. The numerical
      implementation of the near wall functions is made through a finite elements code.

PMID- 29641756
TI  - Yungahelea, a new genus of predaceous midge from northwestern Argentina
      (Culicomorpha: Ceratopogonidae).
AB  - A new monotypic genus and species of predaceous midge from the southernmost area
      of the Argentinean Yungas, Yungahelea australis Spinelli and Ronderos, is
      described and illustrated from male and female adults. It belongs to a group
      containing the Ceratopogonini genera Parabezzia Malloch, Diaphanobezzia Ingram
      and Macfie, Spinellihelea Borkent, Grogan and Picado, Leptohelea Wirth and
      Blanton, and Fittkauhelea Wirth and Blanton. Phylogenetic interpretation
      indicates that Yungahelea is the sister group of Spinellihelea or the clade
      composed by Parabezzia and Diaphanobezzia.

PMID- 29641757
TI  - Invertebrate herbivory on floating-leaf macrophytes at the northeast of
      Argentina: should the damage be taken into account in estimations of plant
      biomass?
AB  - We assessed the damage produced by invertebrate herbivores per leaf lamina and
      per m2 of populations floating-leaf macrophytes of Neotropical wetlands in the
      growth and decay periods, and assessed if the damage produced by the herbivores
      should be taken into account in the estimations of plant biomass of these
      macrophytes or not. The biomass removed per lamina and per m2 was higher during
      the growth period than in decay period in Nymphoides indica and Hydrocleys
      nymphoides, while Nymphaea prolifera had low values of herbivory in growth
      period. During decay period this plant is only present as vegetative propagules.
      According to the values of biomass removed per m2 of N. indica, underestimation
      up to 17.69% should be produced in cases that herbivory do not should be taking
      account to evaluate these plant parameters on this macrophyte. Therefore, for the
      study of biomass and productivity in the study area, we suggest the use of
      corrected lamina biomass after estimating the biomass removed by herbivores on N.
      indica. The values of damage in N. indica emphasize the importance of this
      macrophyte as a food resource for invertebrate herbivores in the trophic networks
      of the Neotropical wetlands.

PMID- 29641758
TI  - Antiedematogenic activity of the indole derivative N-salicyloyltryptamine in
      animal models.
AB  - The N-salicyloyltryptamine (NST) is an indole derivative compound analogue to the
      alkaloid N-benzoyltryptamine. In the present study, the antiedematogenic activity
      of NST was investigated in animal models. Firstly, the acute toxicity for NST was
      assessed according to the OECD Guideline no. 423. The potential NST-induced
      antiedematogenic activity was evaluated by carrageenan-induced paw edema in rats,
      as well as by dextran-, compound 48/80-, histamine-, serotonin-, capsaicine-, and
      prostaglandin E2-induced paw edema in mice. The effect of NST on compound 48/80
      induced ex vivo mast cell degranulation on mice mesenteric bed was investigated.
      No death or alteration of behavioral parameters was observed after administration
      of NST (2000 mg/kg, i.p.) during the observation time of 14 days. The NST (100
      and 200 mg/kg, i.p.) inhibited the carrageenan-induced edema from the 1st to the
      5th hour (**p<0.01; ***p<0.001). The edematogenic activity induced by dextran,
      compound 48/80, histamine, serotonin, capsaicin, and prostaglandin E2 was
      inhibited by NST (100 mg/kg, i.p.) throughout the observation period (**p<0.01;
      ***p<0.001). The pretreatment with NST (50, 100 or 200 mg/kg, i.p) attenuates the
      compound 48/80-induced mast cell degranulation (**p<0.01; ***p<0.001). Thus, the
      inhibition of both mast cell degranulation and release of endogenous mediators
      are probably involved in the NST-induced antiedematogenic effect.

PMID- 29641759
TI  - UV induced surface modification on improving the cytocompatibility of metallocene
      polyethylene.
AB  - Demand for medical implants is rising day by day as the world becomes the place
      for more diseased and older people. Accordingly, in this research, metallocene
      polyethylene (mPE), a commonly used polymer was treated with UV rays for
      improving its biocompatibility. Scanning electron microscopy (SEM) images
      confirmed the formation of crests and troughs, which depicts the improvement of
      surface roughness of mPE substrates caused by UV etching. Accordingly, the
      contact angle measurements revealed that the wettability of mPE-2.5 J/cm2
      (68.09o) and mPE-5 J/cm2 (57.93o) samples were found to be increased compared to
      untreated mPE (86.84o) indicating better hydrophilicity. Further, the UV treated
      surface exhibited enhanced blood compatibility as determined in APTT (untreated
      mPE- 55.3 +/- 2.5 s, mPE-2.5 J/cm2 - 76.7 +/- 4.1 s and mPE-5 J/cm2 - 112.3 +/- 2
      s) and PT (untreated mPE - 24.7 +/- 1.5 s, mPE- 2.5 J/cm2 - 34.3 +/- 1.1 s and
      mPE-5 J/cm2 - 43 +/- 2 s) assay. Moreover, the treated mPE-2.5 J/cm2 (4.88%) and
      mPE-5 J/cm2 (1.79%) showed decreased hemolytic percentage compared to untreated
      mPE (15.40%) indicating better safety to red blood cells. Interestingly, the
      changes in physicochemical properties of mPE are directly proportional to the
      dosage of the UV rays. UV modified mPE surfaces were found to be more compatible
      as identified through MTT assay, photomicrograph and SEM images of the seeded 3T3
      cell population. Hence UV-modified surface of mPE may be successfully exploited
      for medical implants.

PMID- 29641760
TI  - Quantification of anti-nutritional factors and their correlations with protein
      and oil in soybeans.
AB  - Soybeans contain about 30% carbohydrate, mainly consisting of non-starch
      polysaccharides (NSP) and oligosaccharides. NSP are not hydrolyzed in the
      gastrointestinal tract of monogastric animals. These NSP negatively affect the
      development of these animals, especially the soluble fraction. This work aimed to
      establish a method to quantify NSP in soybeans, using high performance liquid
      chromatography (HPLC), and to estimate correlations between NSP,
      oligosaccharides, protein and oil. Sucrose, raffinose + stachyose, soluble and
      insoluble NSP contents were determined by HPLC. Oil and protein contents were
      determined by near-infrared spectroscopy (NIRS). The soluble PNAs content showed
      no significant correlation with protein, oil, sucrose and raffinose + stachyose
      contents, but oligosaccharides showed a negative correlation with protein
      content. These findings open up the possibility of developing cultivars with low
      soluble NSP content, aiming to develop feed for monogastric animals.

PMID- 29641761
TI  - Toxicity and motor changes in Africanized honey bees (Apis mellifera L.) exposed
      to fipronil and imidacloprid.
AB  - This study evaluated the in vitro toxicity and motor activity changes in African
      derived adult honey bees (Apis mellifera L.) exposed to lethal or sublethal doses
      of the insecticides fipronil and imidacloprid. Mortality of bees was assessed to
      determine the ingestion and contact lethal dose for 24 h using probit analysis.
      Motor activities in bees exposed to lethal (LD50) and sublethal doses (1/500th of
      the lethal dose) of both insecticides were evaluated in a behavioral observation
      box at 1 and 4 h. Ingestion and contact lethal doses of fipronil were 0.2316 ?
      0.0626 and 0.0080 ? 0.0021 MUg/bee, respectively. Ingestion and contact lethal
      doses of imidacloprid were 0.1079 ? 0.0375 and 0.0308 ? 0.0218 MUg/bee,
      respectively. Motor function of bees exposed to lethal doses of fipronil and
      imidacloprid was impaired; exposure to sublethal doses of fipronil but not
      imidacloprid impaired motor function. The insecticides evaluated in this study
      were highly toxic to African-derived A. mellifera and caused impaired motor
      function in these pollinators.

PMID- 29641762
TI  - Changes in adipose cells of Longissimus dorsi muscle in Iberian pigs raised under
      extensive conditions.
AB  - Twenty-four Iberian castrated male pigs were used to characterize and evaluate
      the effect of the duration of "Montanera" in the adipocytes size and its relation
      with the backfat thickness and intramuscular fat. The animals were fed under
      extensive conditions during 30, 60 and 90 days in the "Dehesa" before
      slaughtered. Carcass weight, percentage of intramuscular fat, thickness of
      backfat and its three layers and adipocytes size of the intramuscular fat were
      obtained. The group which expended 90 days on fattening obtained the highest
      adipocytes, with an area higher by a 50% than those that only expended 30 days.
      The differences in diameter and perimeter adipocyte were not as marked as area. A
      significant positive correlation between the diameter, area and perimeter of
      adipocyte with the backfat thickness were found. The fat cells in Iberian pig
      hypertrophy during the "montanera stage", being this increase significant from
      month to month in this period of fattening. Also, this adipocyte increase is
      correlated with the animal weight. The correlation between adipocyte size and
      inner layer of backfat shows that the inner layer obtained in live pig by
      ultrasound techniques could be a good marker of fat infiltration in pigs
      fattening in "montanera" system.

PMID- 29641763
TI  - Estimating Stand Height and Tree Density in Pinus taeda plantations using in-situ
      data, airborne LiDAR and k-Nearest Neighbor Imputation.
AB  - Accurate forest inventory is of great economic importance to optimize the entire
      supply chain management in pulp and paper companies. The aim of this study was to
      estimate stand dominate and mean heights (HD and HM) and tree density (TD) of
      Pinus taeda plantations located in South Brazil using in-situ measurements,
      airborne Light Detection and Ranging (LiDAR) data and the non- k-nearest neighbor
      (k-NN) imputation. Forest inventory attributes and LiDAR derived metrics were
      calculated at 53 regular sample plots and we used imputation models to retrieve
      the forest attributes at plot and landscape-levels. The best LiDAR-derived
      metrics to predict HD, HM and TD were H99TH, HSD, SKE and HMIN. The Imputation
      model using the selected metrics was more effective for retrieving height than
      tree density. The model coefficients of determination (adj.R2) and a root mean
      squared difference (RMSD) for HD, HM and TD were 0.90, 0.94, 0.38m and 6.99,
      5.70, 12.92%, respectively. Our results show that LiDAR and k-NN imputation can
      be used to predict stand heights with high accuracy in Pinus taeda. However,
      furthers studies need to be realized to improve the accuracy prediction of TD and
      to evaluate and compare the cost of acquisition and processing of LiDAR data
      against the conventional inventory procedures.

PMID- 29641764
TI  - Relationships of rice yield and quality based on genotype by trait (GT) biplot.
AB  - An experiment was conducted to examine the influencing characters on rice by
      using 64 rice genotypes, including four local landraces, four released cultivars
      and 56 mutant lines (M5) derived from these genotypes, with application of the
      genotype by trait (GT) biplot methodology. The first two principal components
      (PC1 and PC2) accounted for 46.6% of total variation in 64 genotypes. The polygon
      view of GT biplot suggested seven sections for 64 genotypes. The vertex G38 had
      good amounts of grain yield, panicle length, hundred grain weight, internodes
      length, plant height and fertility percentage. Generally based on vector view it
      was demonstrated that the selection of high grain yield would be performed via
      thousand grain weight, panicle weight and number of filled grain per panicle.
      These traits should be considered simultaneously as effective selection criteria
      evolving high yielding rice genotypes because of their large contribution to
      grain yield. The genotypes G2, G4 and G7 could be considered for the developing
      of desirable progenies in the selection strategy of rice improvement programs.
      This study revealed GT biplot can graphically display the interrelationships
      among traits. In conclusion, it is recommended the use of GGE biplot to identify
      superior genotypes for simultaneous improvement of several traits.

PMID- 29641765
TI  - Timing and placement of cattle manure and/or gliricidia affects cotton and
      sunflower nutrient accumulation and biomass productivity.
AB  - Organic fertilizers are a viable alternative to increase oilseed productivity in
      family agriculture systems. The study aimed to evaluate the effects of timing and
      placement of cattle manure and/or gliricidia (Gliricidia sepium Jacq. Walp)
      prunings on cotton (Gossipium hirsutum L.) and sunflower (Helianthus annuus L.)
      nutrient accumulation and biomass productivity. Experiments were carried out in
      2010 and 2011 in Taperoa, Paraiba, Brazil. The organic fertilization treatments
      were: GI - gliricidia incorporated before planting; GS - gliricidia applied on
      surface 45 days after planting (DAP); MI + GI - manure and gliricidia
      incorporated before planting; MI + GS - manure incorporated before planting and
      gliricidia applied on the surface 45 DAP; MI - manure incorporated before
      planting; and T - with no organic fertilization. In 2010, treatment MI + GS
      increased N, P, and K accumulation in cotton (12 and 7 kg ha-1) as well as in
      sunflower (20 and 29 kg ha-1). In 2011, GI and GS treatments resulted in higher
      N, P, K accumulations in both crops. The highest cotton productivity in 2010 was
      obtained with MI + GS treatment (198 kg ha-1) and in 2011 with GS treatment (594
      kg ha-1). For sunflower, MI + GS treatment yielded the highest productivity in
      2010 (466 kg ha-1) and GI treatment in 2011 (3542 kg ha-1). GI and MI + GS
      treatments increased total biomass productivity for cotton and sunflower. The
      treatment that combined both cattle manure incorporated into the soil before
      planting and gliricidia applied on the surface 45 days after planting was the
      most viable management strategy.

PMID- 29641766
TI  - Heartwood and sapwood in eucalyptus trees: non-conventional approach to wood
      quality.
AB  - This study evaluated the quality of heartwood and sapwood from mature trees of
      three species of Eucalyptus, by means of the qualification of their proportion,
      determination of basic and apparent density using non-destructive attenuation of
      gamma radiation technique and calculation of the density uniformity index. Six
      trees of each species (Eucalyptus grandis - 18 years old, Eucalyptus tereticornis
      - 35 years old and Corymbia citriodora - 28 years old) were used in the
      experimental program. The heartwood and sapwood were delimited by macroscopic
      analysis and the calculation of areas and percentage of heartwood and sapwood
      were performed using digital image. The uniformity index was calculated following
      methodology which numerically quantifies the dispersion of punctual density
      values of the wood around the mean density along the radius. The percentage of
      the heartwood was higher than the sapwood in all species studied. The density
      results showed no statistical difference between heartwood and sapwood.
      Differently from the density results, in all species studied there was
      statistical differences between uniformity indexes for heartwood and sapwood
      regions, making justifiable the inclusion of the density uniformity index as a
      quality parameter for Eucalyptus wood.

PMID- 29641767
TI  - Statistical tools application on dextranase production from Pochonia
      chlamydosporia (VC4) and its application on dextran removal from sugarcane juice.
AB  - The aim of this study was to optimize the dextranase production by fungus
      Pochonia chlamydosporia (VC4) and evaluate its activity in dextran reduction in
      sugarcane juice. The effects, over the P. chlamydosporia dextranase production,
      of different components from the culture medium were analyzed by Plackett-Burman
      design and central composite design. The response surface was utilized to
      determine the levels that, among the variables that influence dextranase
      production, provide higher production of these enzymes. The enzymatic effect on
      the removal of dextran present in sugarcane juice was also evaluated. It was
      observed that only NaNO3 and pH showed significant effect (p<0.05) over
      dextranase production and was determined that the levels which provided higher
      enzyme production were, respectively, 5 g/L and 5.5. The dextranases produced by
      fungus P. chlamydosporia reduced by 75% the dextran content of the sugarcane
      juice once treated for 12 hours, when compared to the control treatment.

PMID- 29641768
TI  - Apparent digestibility of conventional and alternative feedstuffs by hybrid
      tambacu juveniles.
AB  - The apparent digestibility coefficients (ADC's) of dry matter (DM), crude protein
      (CP), and gross energy (GE) of conventional feedstuffs (cottonseed meal-CSM,
      soybean meal-SBM, wheat bran-WHB, corn-COR) and regional alternative feedstuffs
      (common bean residue meal-CBR, mesquite meal-MES, pasta by-product meal-PBM) were
      determined for hybrid juvenile tambacu Colossoma macropomum * Piaractus
      mesopotamicus. The apparent DM and GE digestibility of feedstuffs decreased
      (p<0.05) as fiber content of the ingredients increased. No differences (p>0.05)
      were found among ADC's of PBM and COR. The lowest CP ADC among energy sources was
      observed in MES; the lowest CP ADC among plant protein sources was observed in
      CBR. Information about the ADC's of conventional and alternative feedstuffs for
      tambacu is essential to formulate low-cost diets and can contribute to regional
      development.

PMID- 29641769
TI  - Modification of the Alere GIARDIA Ag TEST immunochromatography KIT methodology
      for its use in frozen fecal sediment of dogs and cats.
AB  - Giardia duodenalis is a worldwide intestinal parasite and is one of the most
      frequent protozoa species infecting dogs and cats. This study aimed to modify the
      methodology of Alere GIARDIA Ag TEST KIT for its use in frozen fecal sediments
      with different storage times in a freezer (-20 degrees C), thus expanding the
      range of use of this methodology. One hundred fecal sediments from dogs (n=50)
      and cats (n=50) previously examined by optical microscopy for Giardia cysts were
      selected for this study. The agreement between the modified immunochromatography
      and microscopy results was calculated by Kappa coefficient. To evaluate the
      performance of the modified immunochromatography assay on samples with different
      storage time, the fecal sediments were divided into three groups according to the
      time of storage in a freezer: (a) <= 1 year (n=37); (b) > 1 year and <= 3 years
      (n=39); (c) > 10 years (max. 13 years) (n=24). The results obtained by the
      modified immunochromatography assay demonstrates a higher sensitivity of this
      technique when compared with microscopy, regardless of the frozen storage time.
      These results allow for the use of this methodology in a greater scope of
      analysis, especially in frozen fecal sediment triage in sample collections,
      enabling epidemiological and comparative analysis along different decades.

PMID- 29641770
TI  - Optimization of RT-PCR reactions in studies with genes of lignin biosynthetic
      route in Saccharum spontaneum.
AB  - Saccharum spontaneum has been used for the development of energy cane a crop
      aimed to be used for the production of second-generation ethanol, or
      lignocellulosic ethanol. Lignin is a main challenge in the conversion of cell
      wall sugars into ethanol. In our studies to isolate the genes the lignin
      biosynthesis in S. spontaneum we have had great difficulty in RT-PCR reactions.
      Thus, we evaluated the effectiveness of different additives in the amplification
      of these genes. While COMT and CCoAOMT genes did not need any additives for other
      genes there was no amplification (HCT, F5H, 4CL and CCR) or the yield was very
      low (CAD and C4H). The application of supplementary cDNA was enough to overcome
      the non-specificity and low yield for C4H and C3H, while the addition of 0.04%
      BSA + 2% formamide was effective to amplify 4CL, CCR, F5H and CCR. HCT was
      amplified only by addition of 0.04% BSA + 2% formamide + 0.1 M trehalose and
      amplification of PAL was possible with addition of 2% of DMSO. Besides
      optimization of expression assays, the results show that additives can act
      independently or synergistically.

PMID- 29641771
TI  - Holistic Critical Thinking in the Nursing Diagnostic Process.

PMID- 29641772
TI  - Portuguese Primary Care physicians response rate in surveys: A systematic review.
AB  - INTRODUCTION: Surveys are a useful tool in primary care. However, low response
      rates can introduce selection bias, impairing both external and internal
      validity. The aim of this study was to assess the average response rate in
      surveys with Portuguese general practitioners (GPs). METHOD: We searched the
      Medline, Web of Science, Scopus, Embase, PsychInfo, SciELO, IndexRMP, RCAAP,
      Revista Portuguesa de Medicina Geral e Familiar, Acta Medica Portuguesa and the
      proceedings of conferences of general practice from incepton to December 2016. We
      included all postal, e-mail, telephone and personal surveys to primary care
      physicians without language restrictions. We did not assess risk of bias of
      included studies, since the main outcome was survey response rate. We performed
      planned subgroup analyses of the use of monetary incentives, the use of non
      monetary incentives, survey delivery modes and prior contact with participants.
      RESULTS: A total of 1,094 papers were identified and 37 studies were included in
      this review. The response rate in surveys done to Portuguese GPs was 56% (95CI 47
      64%). There was substantial heterogeneity among included studies (I2=99%), but
      subgroup analysis did not explain this heterogeneity. CONCLUSION: Consistent with
      other published studies, the average response rate in surveys done with
      Portuguese GPs was 56%, with substantial variation among studies. Use of monetary
      incentives, one of the most effective strategies to increase response rates, was
      not present in any of the included studies.

PMID- 29641773
TI  - Breast cancer and hormonal contraception: Should we rethink our concepts?

PMID- 29641774
TI  - Dyslipidemia and maternal obesity: Prematurity and neonatal prognosis.
AB  - OBJECTIVE: To identify the changes caused by dyslipidemia and obesity in
      pregnancy suggesting causes for premature birth, and the prognosis for the
      newborn. METHOD: Systematic review based on the Medline, Lilacs, Embase and
      Cochrane library databases between 1996 and 2016. The search for studies included
      the following keywords: "dyslipidemia, pregnancy, obesity, preterm birth." A
      protocol was programmed and a protocol for inclusion/exclusion of studies was
      implemented. RESULTS: Of the 5,789 articles initially selected between March 1996
      and July 2016, only 32 were in accordance with the established criteria. Of
      these, 28.12% discussed risk factors of prematurity; 37.50%, metabolic
      alterations and gestational dyslipidemia; 21.87%, dyslipidemic complications in
      preterm birth; and 12,50%, lipid metabolism, glycemic and placental transfer.
      CONCLUSION: There is a reduced adaptation of obese pregnant women to the
      metabolic changes of gestation. This favors dyslipidemic intercurrences in the
      mother, which, directly or indirectly, suggests the occurrence of premature
      births and high lipid transfer to the fetus. Therefore, preterm newborns, whose
      mothers were dyslipidemic during pregnancy, have greater risk of epicardial fat,
      both in early (first year of life) and in later (adult) phases of life.

PMID- 29641775
TI  - Is serum angiotensin converting enzyme level a useful non-invasive marker for
      liver fibrosis in patients with chronic hepatitis C?
AB  - OBJECTIVE: Chronic hepatitis C (CHC) continues to be a critical problem. The
      liver fibrosis score is the most valuable tool in determining treatment and
      prognosis. Liver biopsy is still considered a gold method but, due to unmet
      needs, new non-invasive markers are required. The aim of this study was to
      investigate any possible relationship between serum angiotensin-converting enzyme
      (ACE) levels and the stages of liver fibrosis in patients with CHC. METHOD: A
      total 100 CHC and 100 healthy subjects were enrolled in this study. The
      relationship between serum ACE level and the stages liver fibrosis was
      investigated using three different formats, as follows: (group [G]-I, classic
      Ishak's Score from F1 to F6; G-II, mild [F1-2], moderate [F3-4] and severe [F5
      6]; G-III, mild [<= F2] and advanced [F > 2]). The clinical usability of serum
      ACE level for both groups was also investigated. RESULTS: Median serum ACE levels
      were higher in the healthy group than in CHC (42.5 [7-119] vs. 36 [7-91] U/I,
      p=0.002). There was no statistical difference among the three different fibrosis
      groups (G-I, G-II, G-III, p=0.797, p=0.986, and p=0.874) and no correlation
      between serum ACE level and the stages of liver fibrosis (r=0.026, p=0.923). The
      usability of serum ACE for evaluated patients with CHC and healthy subjects were
      calculated as 47% and 64%, respectively. CONCLUSION: Our study indicated that
      there is no relationship or correlation between serum ACE levels and stages of
      liver fibrosis in patients with CHC. The assessment of serum ACE level using
      genetically corrected reference values may provide more accurate results.

PMID- 29641776
TI  - A review on the relationship between marital adjustment and maternal attachment.
AB  - OBJECTIVE: To determine the relationship between marital adjustment of mothers
      who have babies between 1-4 months old and their maternal attachment; as well as
      the relationship of maternal attachment and marital adjustment with
      sociodemographic characteristics. METHOD: The research is descriptive and
      correlational. Its sample consists of 113 mothers. Maternal Attachment Index
      (MAI) and Marital Adjustment Scale (MAS) are used as data collection tools.
      RESULTS: We found that, for mothers who participated in this research, the
      average level of maternal attachment is 92.17 +/- 8.49, and the average level of
      marital adjustment is 43.06 +/- 7.90. We discovered that the maternal attachment
      level is higher for mothers who have completed high school and university, those
      who breastfeed their babies exclusively and whose spouses help care for the baby.
      We also discovered that the Marital Adjustment Score is higher among mothers who
      are employed, get married by companionship (not arranged), continue attending
      pregnancy classes and whose duration of marriage is between 1-5 years and 10-15
      years. There is weak positive relationship (r=0.38; p=0.00) between marital
      adjustment and maternal attachment; and the regression analysis that is run to
      explain this relationship is statistically significant (F=26.131; p<0.05).
      CONCLUSION: In our study, the level of maternal attachment was high, while the
      level of marital adjustment was liminal. There are many factors affecting
      sociodemographic characteristics, pregnancy and baby care. The level of marital
      adjustment for mothers increases the maternal attachment.

PMID- 29641777
TI  - The clinical efficacy and safety of paclitaxel combined with avastin for NSCLC
      patients diagnosed with malignant pleural effusion.
AB  - OBJECTIVE: The current study aimed to investigate the clinical efficacy of
      paclitaxel combined with avastin for non-small cell lung cancer (NSCLC) patients
      diagnosed with malignant pleural effusion (MPE). METHOD: Total of 33 patients
      diagnosed with NSCLC as well as malignant pleural effusion were included. All of
      them received paclitaxel (175 mg/m2) and avastin (5 mg/kg). Clinical efficacy was
      evaluated using the total response rate, overall survival, progression-free
      survival and changes in MPE volume. Adverse events and rates of toxicities were
      examined as well. RESULTS: The total response rate reached 77% while the overall
      survival and the median progression-free survival were respectively 22.2 months
      and 8.4 months. Toxicities of grade 3-4 consisted of neutropenia in 57% of
      patients, anemia in 17% of them, febrile neutropenia in 11%, as well as anorexia
      in 7%. No treatment-correlated deaths were found. CONCLUSION: Paclitaxel combined
      with avastin decreased MPE volume and increased survival rate of NSCLC patients
      via inhibiting vascular endothelial growth factor expression.

PMID- 29641778
TI  - Efficacy and safety of ceftazidime-avibactam in the treatment of complicated
      intra-abdominal infections (CIAIs) and complicated urinary tract infections
      (CUTIs): A meta-analysis of randomized controlled trials.
AB  - OBJECTIVE: The aim of this study was to assess the efficacy and safety of
      ceftazidime-avibactam in the treatment of complicated intra-abdominal infections
      (CIAIs) and complicated urinary tract infections (CUTIs) with meta-analysis
      method. METHOD: We included six randomized clinical trials identified from
      Medline, Embase, Cochrane Library, "ISRCTN Register" and "ClinicalTrials.gov"
      which compared ceftazidime-avibactam with comparison group. The meta-analysis was
      performed using Review Manager software version 5.3. RESULTS: Ceftazidime
      avibactam versus active comparisons demonstrated a statistically significant
      higher rate of microbiological response success on microbiological evaluable
      populations at the test-of-cure visit (95CI 1.10-2.38, p=0.02) and late-follow-up
      visit (95CI 1.09-2.23, p=0.02) for the treatment of CUTIs. Ceftazidime-avibactam
      versus active comparisons demonstrated a statistically significant higher rate of
      microbiological response success on EME populations at the test-of-cure visit
      (95CI 1.08-4.27, p=0.03) and late-follow-up visit (OR=1.75, 95CI 1.33-2.29,
      p<0.0001) for the treatment of CUTIs. Similar results were obtained at the late
      follow-up visit (OR = 1.58, 95CI 1.26-1.97, p<0.0001) on microbiologically
      modified intent-to-treat (mMITT) populations for the treatment of CUTIs. We can
      find better eradication rates for E. coli and Klebsiella pneumoniae based on
      mMITT populations. In terms of AEs, SAEs and mortality, ceftazidime-avibactam had
      a safety and tolerability profile broadly similar to the comparison group.
      CONCLUSION: This meta-analysis provides evidence of the efficacy of ceftazidime
      avibactam as a potential alternative for the treatment of patients with CUTIs,
      and CIAIs.

PMID- 29641779
TI  - Quality of life in a sample of Brazilian adults using the generic SF-12
      questionnaire.
AB  - OBJECTIVE: This study describes the summary scores of the Short Form-12 (SF-12)
      questionnaire, according to socio-demographic factors obtained in a probabilistic
      and representative sample of the Brazilian urban population. METHOD: Five
      thousand (5,000) individuals, over the age of 15, were assessed in 16 capital
      cities, in the five regions of the country. The selection of households was
      random. Face-to-face approach was applied in the household interviews. The SF-12
      questionnaire was used to assess quality of life. Demographic and socioeconomic
      characteristics were also evaluated: gender, age, marital status, skin color,
      region of the country and use of the public health service. RESULTS: The mean
      value (SD) of the SF-12 for the entire population was 49.3 (8.7) for the physical
      component (PCS-12) and 52.7 (9.7) for the mental component (MCS-12). Statistical
      differences were found for gender (PCS-12 and MCS-12), age (PCS-12) and working
      status (PCS-12 and MCS-12). Women, elderly, widowed and unemployed individuals,
      those with lower income and with complaints in the last seven days showed lower
      mean values (PCS-12 and MCS-12). CONCLUSION: From this point forward, we can
      provide the basis for comparisons with future research that use the SF-12 for
      quality of life assessment in Brazil. The Brazilian population has a lower degree
      of quality of life related do the physical component, and the SF-12 is a useful
      and discriminative instrument for assessing quality of life in different socio
      demographic groups.

PMID- 29641780
TI  - Selenium supplementation in pediatric patients using parenteral nutrition: Is it
      time to do something?
AB  - OBJECTIVE: To analyze the nutritional status of selenium and verify the effect of
      its supplementation in pediatric patients during 14 days of parenteral nutrition
      (PN). METHOD: This is a series of cases with patients followed for two weeks
      while using PN. Data collection was performed at the beginning (T0), in the 7th
      (T1) and 14th days of PN (T2). The supplemented group received 2 ug/kg/day of
      selenous acid. Weight and height were measured for nutritional status assessment.
      Tests requested: plasma selenium, albumin, pre-albumin, C-reactive protein (CRP),
      total cholesterol and HDL-cholesterol. RESULTS: Fourteen (14) patients with
      inflammatory process and with low or very low weight for their ages were
      evaluated. In both groups (with and without supplementation), all patients had
      low selenium levels. Median plasma selenium concentrations were 17.4 ug/L (T0),
      23.0 ug/L (T1) and 20.7 ug/L (T2). Increase and reduction of selenium occurred
      both in patients with high CRP and in those presenting normalization of this
      parameter. CONCLUSION: Lower plasma selenium levels have been detected since the
      start of the research and supplementation (2 ug/kg/day of selenous acid) was not
      to enough to approach the reference values.

PMID- 29641781
TI  - Osteoporotic vertebral compression fracture - Treatment with kyphoplasty and
      vertebroplasty.

PMID- 29641782
TI  - Esophageal lichen planus: An unusual cause of dysphagia in the elderly.
AB  - An 82-year-old man sought our service with dysphagia and was referred for upper
      endoscopy with biopsies, which evidenced multiple ulcers of the esophagus and
      oropharinx. Histopathology confirmed the unusual diagnosis of esophageal lichen
      planus. The correct clinical suspicion of this disease can facilitate the
      diagnosis and guide specific treatment, which can drastically change the natural
      course of the disease.

PMID- 29641783
TI  - Fulminant liver failure in a street runner: Effects of heat stroke.
AB  - We present a clinical case of liver failure induced by heat stroke.

PMID- 29641784
TI  - Current guidelines for prostate cancer screening: A systematic review and minimal
      core proposal.
AB  - OBJECTIVE: Considering the importance of screening for prostate cancer, the
      possibility of damage resulting from indiscriminate screening and the difficulty
      of disclosure and adherence to the main guidelines on the subject, we aimed to
      identify current guidelines, look for common approaches and establish a core of
      conducts. METHOD: Systematic review of the literature on screening practice
      guidelines for prostate cancer searching the databases PubMed, Lilacs and Google
      Scholar and active search in the sites of several national health entities.
      RESULTS: Twelve (12) guidelines were selected, whose analysis resulted in the
      identification of six common points of conduct, with the following minimum core
      of recommendations: (1) screening indication or not: must be individualized, and
      preceded by an informed decision; (2) tests used: PSA with or without rectal
      digital examination; (3) age at which initiate testing in men in general risk: 50
      55 years; (4) age at which to initiate testing in men at increased risk: 40-45
      years; (5) the interval between screening: annual or biennial; and (6) age at
      which to discontinue testing: 70 years-old or life expectancy less than 10 years.
      CONCLUSION: Although there are differences between them, it was possible to
      establish a minimum core of conducts that may be useful in the daily practice of
      the physician.

PMID- 29641785
TI  - Both glucocentric and cardiocentric approaches are necessary for a resilient
      disease such as diabetes.
AB  - Diabetes mellitus (DM) is a complex disease that compromises almost all systems
      in the human organism. Independently of the intrinsic mechanisms, the source of
      all consequences of DM is hyperglycemia, a condition associated to intense
      metabolic changes that will lead to increased morbidity and mortality in the long
      term. Several different therapeutic hypoglycemic oral agents were developed and
      significantly facilitated the treatment of hyperglycemia acting at different
      sites, since patients could take more than one agent. This glucocentric approach
      was somehow criticized as those hypoglycemic drugs have shown weaker than
      expected benefits in terms of cardiovascular outcomes and there was a sub use of
      statins and antihypertensive agents in this population. On the other hand, the
      catastrophic cardiovascular consequences of hypoglycemia in older adults
      submitted to tight glycemic control and the results of recent clinical trials
      that showed impressive reduction in cardiovascular outcomes with less potent
      antidiabetic agents seem to pave the way to a cardiocentric approach including a
      lax treatment of DM. Interestingly, the results obtained in recent studies with
      SGLT2 inhibitors are being mostly attributed to mechanisms other than its
      hypoglycemic effect in spite of including patients at high cardiovascular risk
      already taking hypoglycemic agents. Considering the worldwide growing number of
      patients with diabetes, caregivers must follow a dialectical thinking and choose
      a synthesis approach where glycemic control is the first and foremost target to
      be achieved, followed by control of cardiovascular risk factors.

PMID- 29641786
TI  - Human leishmaniasis in Brazil: A general review.
AB  - Leishmaniasis is a disease with ample clinical spectrum and epidemiological
      diversity and is considered a major public health problem. This article presents
      an overview of the transmission cycles, host-parasite interactions, clinical,
      histological and immunological aspects, diagnosis and treatment of various forms
      of the human disease.

PMID- 29641787
TI  - Nasal mites (Mesostigmata, Rhinonyssidae) in Sternidae (Aves: Charadriiformes) on
      the southern Coast of Brazil.
AB  - Six species of birds of the family Sternidae are often found on the southern
      coast of South America. Sterna trudeaui, S. hirundinacea, Thalasseus maximus, T.
      acuflavidus and Sternula superciliaris are South American residents and Sterna
      hirundo, a Nearctic migrant. At least 500 species of nasal mites have been
      described around the world, and Rhinonyssidae is the most diverse family. These
      mites are bloodsucking endoparasites that inhabit the respiratory system of
      birds. This study aimed to report on occurrences of nasal mites in Sternidae on
      the southern coast of Brazil. Of the 106 birds analyzed, 8.5% (9 birds) were
      parasitized by nasal mites. This report provides the first record in the
      Neotropical region for two mite species, Sternostoma boydi and Larinyssus
      orbicularis parasitizing Thalasseus acuflavidus and Sternula superciliaris. No
      nasal mites were found in Sterna trudeaui or Thalasseus maximus. One host
      individual (T. acuflavidus) was parasitized by two species of nasal mites, S.
      boydi and L. orbicularis.

PMID- 29641788
TI  - Molecular detection of Anaplasmataceae agents in Dasyprocta azarae in
      northeastern Brazil.
AB  - Recently, the importance of wild-living rodents for maintenance of pathogens of
      the family Anaplasmataceae in the environment was investigated. These mammals
      play a role as reservoirs for these pathogens and act as hosts for the immature
      stages of tick vectors. The aim of the present study was to investigate the
      prevalence of Ehrlichia sp. and Anaplasma sp. in 24 specimens of Azara's agouti
      (Dasyprocta azarae) that had been trapped in the Itapiraco Environmental Reserve,
      in Sao Luis, Maranhao, northeastern Brazil, using molecular methods. Four animals
      (16.7%) were positive for Ehrlichia spp. in nested PCR assays based on the 16S
      rRNA gene. In a phylogenetic analysis based on the 16S rRNA gene, using the
      maximum likelihood method and the GTRGAMMA+I evolutionary model, Ehrlichia sp.
      genotypes detected in Azara's agoutis were found to be closely related to E.
      canis and to genotypes relating to E. canis that had previously been detected in
      free-living animals in Brazil. The present work showed the first molecular
      detection of Ehrlichia sp. in Azara's agoutis in Brazil.

PMID- 29641789
TI  - Prevalence of Eimeria spp. in calves from dairy farms in northern Parana state,
      Brazil.
AB  - Bovine coccidiosis is a disease of major importance in cattle herds across the
      world. The disorder mainly affects young calves, and E. bovis and E. zuernii are
      considered the most pathogenic species of the genus, however, E. alabamensis have
      been described in grazing calves. In this study, the prevalence of Eimeria spp.
      was evaluated in calves on dairy farms in the northern region of the state of
      Parana, Brazil. Four hundred calves on 44 dairy farms were tested for the
      presence of coccidian oocysts. The positives were re-examined and the oocysts
      were morphometrically analyzed for species identification. All the farms were
      contaminated and 205 animals (51.25%) presented Eimeria spp. oocysts. Among
      these, 146 animals (71.22%) were co-infected by two or more species of coccidia.
      Ten species of Eimeria were identified: E. bovis (in 30.25% of the positive
      samples), E. alabamensis (26.75%), E. zuernii (22.00%), E. ellipsoidalis
      (18.50%), E. auburnensis (13.75%), E. canadensis (8.00%), E. cylindrica (7.25%),
      E. subspherica (5.00%), E. bukidnonensis (3.00%) and E. brasiliensis (0.75%).
      This study demonstrates the high prevalence of Eimeria spp. in the northern
      region of Parana, Brazil, and detection for the first time in our region the
      pathogenic species E. alabamensis.

PMID- 29641790
TI  - Morphological effects on helminth parasites caused by herbicide under
      experimental conditions.
AB  - Helminth parasites have been studied as potential accumulators for different
      pollutants. Echinostoma paraensei is a foodborne trematode whose vertebrate host,
      the rodent Nectomys squamipes, is naturally exposed to environmental pesticides.
      However, little information exists regarding the pesticide's effects on
      helminths. This study investigated the morphological effects on the trematode, E.
      paraensei, after experimental Roundup(r) herbicide exposure, in concentrations
      below those recommended for agricultural use. After two hours of exposure,
      scanning electron microscopy (SEM) showed changes to the tegument, such as
      furrowing, shrinkage, peeling, spines loss on the peristomic collar, and
      histopathological evidence of altered cells in the cecum and acinus vitelline
      glands with vacuoles and structural changes to the muscular layers. Glycidic
      content was decreased, primarily in the connective tissue. As E. paraensei is an
      intestinal parasite of the semi-aquatic wild rodent, N. squamipes, it is
      predisposed to pesticide exposure resulting from agricultural practices.
      Therefore, we emphasize the need to evaluate its impact on helminth parasites,
      due to their pivotal role in regulating host populations.

PMID- 29641791
TI  - Comparative study of three xenic media culture for cultivation of Balantidium
      coli strains.
AB  - The aim of the present study was to evaluate the growth rate of Balantidium coli
      in three xenic media cultures. Between 2013 and 2015, 10 B. coli isolates
      obtained from feces of Cynomolgus macaques, and 30 isolates from feces of pigs
      were studied. An inoculum of 500 trophozoites was transferred to tubes containing
      LES, TYSGM-9 and Pavlova media. These cultures were evaluated at incubation times
      of 24, 48, 72 and 96 hours. In most of strains analyzed wasn't showed significant
      difference in the growth rate comparing TYSGM-9 and Pavlova media (Wilcoxon
      p>0.016). In Pavlova medium, the trophozoites showed a maximum growth at 72 hours
      with significant difference when compared with the times of 24 h and 96 h
      (Wilcoxon <0.008). In LES, viable trophozoites were observed until 24 hours, with
      a significant difference (Friedman p<0.05, Wilcoxon p<0.016) in the number of
      parasite cells compared with Pavlova and TYSGM-9 media cultures. Thus, LES medium
      seemed to be less adequate than the other media for maintenance of B. coli.
      Despite the satisfactory results in TYSGM-9, Pavlova medium was considered ideal
      for the maintenance of this protozoan strain, guaranteeing the viability of the
      parasite with subculture every three days, presenting lower costs.

PMID- 29641793
TI  - Endoparasites in domestic animals surrounding an Atlantic Forest remnant, in Sao
      Paulo State, Brazil.
AB  - Morro do Diabo State Park (MDSP) is a significant remnant of the Atlantic Rain
      Forest in Brazil and is surrounded by rural properties. In that area, wild and
      domestic animals and humans are in close contact, which facilitates the two-way
      flow of infectious diseases among them. We assessed endoparasites in domestic
      livestock from all rural properties surrounding MDSP. There were sampled 197
      cattle, 37 horses, 11 sheep, 25 swine, 21 dogs, one cat and 62 groups of chickens
      from 10 large private properties and 75 rural settlements. Eimeria spp. was
      present in almost all hosts, excepted in horses, dogs and cats. Giardia cysts
      were present only in cattle. Nematodes were found in swine, ruminants and horses
      in high prevalence. Ancylostoma, Toxocara and Sarcocystis were found in dogs.
      Chickens were found with coccidia, Ascaridida and Capillaria spp.. These
      parasites can cause malnutrition and reproductive disorders for their hosts.
      Strategies to prevent and control the spread of endoparasites can improve
      wildlife, animal and human health in this area.

PMID- 29641794
TI  - Neospora caninum in properties in the west region of Parana, Brazil: prevalence
      and risk factors.
AB  - Neospora caninum is a heteroxenous protozoa, whose definitive hosts are canids
      and intermediate hosts are herbivores, and is of great importance in cattle. The
      objectives of this study were to determine the prevalence of N. caninum in dairy
      cattle and dogs, to detect the presence of the protozoa at the molecular level in
      aborted fetuses, and to identify the risk factors associated with infection in
      properties in the western region of the state of Parana. For this study, 600
      bovine serum samples from 60 properties, 163 canine serum samples from 52
      properties and 17 bovine fetuses from nine properties were collected. Data were
      collected using an epidemiological questionnaire to verify the risk factors.
      Serum samples were analyzed using the indirect fluorescent antibody test. Fetal
      tissues were analyzed using polymerase chain reaction and subsequent DNA
      sequencing. Of the bovine samples, 23.67% were positive for N. caninum. Among the
      canine samples, 11.66% were positive for N. caninum. Risk factors in cattle were
      history of abortion, low milk production, extensive breeding, and Jersey breed
      (p<0.05). Protozoan DNA was detected in 52.94% of the 17 fetuses and the
      sequencing presented high similarity with N. caninum.

PMID- 29641795
TI  - Detection and molecular characterization of Cryptosporidium spp. in captive
      canaries (Serinus canaria) using different diagnostic methods.
AB  - This study used several diagnostic methods to examine the occurrence of and
      molecularly characterize Cryptosporidium spp. in captive canaries (Serinus
      canaria) in southern and southeastern Brazil. A total of 498 fecal samples were
      purified by centrifugal-flotation using Sheather's solution. Cryptosporidium spp.
      diagnosis was performed using three diagnostic methods: malachite green negative
      staining, nested PCR targeting the 18S rRNA gene, followed by sequencing the
      amplified fragments, and duplex real-time PCR targeting the 18S rRNA specific to
      detect Cryptosporidium galli and Cryptosporidium avian genotype III. The overall
      positivity for Cryptosporidium spp. (total samples positive in at least one
      protocol) from the microscopic analysis, nested PCR and duplex real-time PCR
      protocol results was 13.3% (66/498). The positivity rates were 2.0% (10/498) and
      4.6% (23/498) for Cryptosporidium spp. by microscopy and nested PCR,
      respectively. Sequencing of 20 samples amplified by nested PCR identified C.
      galli (3.0%; 15/498), Cryptosporidium avian genotype I (0.8%; 4/498) and
      Cryptosporidium avium (0.2%; 1/498). Duplex real-time PCR revealed a positivity
      of 7.8% (39/498) for C. galli and 2.4% (12/498) for avian genotype III. Malachite
      green negative staining differed significantly from nested PCR in detecting
      Cryptosporidium spp. Duplex real-time PCR was more sensitive than nested
      PCR/sequencing for detecting gastric Cryptosporidium in canaries.

PMID- 29641796
TI  - Control of sheep gastrointestinal nematodes using the combination of Duddingtonia
      flagrans and Levamisole Hydrochloride 5.
AB  - The objective was to evaluate the action of D. flagrans pellets in association
      with Levamisole Hydrochloride 5% for controlling sheep gastrointestinal nematodes
      in the northeastern Brazil. Three groups of six sheep each were formed: group 1
      received 3 g of the pellets (0.6 g of D. flagrans mycelium) for each 10 kg b.w.,
      twice a week for six months, and deworming with Levamisole Hydrochloride 5% when
      EPG >= 1500; group 2 received a dosage of Levamisole Hydrochloride 5% when EPG >=
      1500; and group 3 received 3 g of pellets without fungi for each 10 kg b.w.,
      twice a week for six months. EPG counts, larval cultures, packed cell volume
      (PCV) and weighing were performed every 15 days; monthly, samples of grass from
      each paddock were collected. The mean EPG of the groups began to statistically
      differ from day 30 (p < 0.05). Group 1 required less deworming with Levamisole
      Hydrochloride 5% and showed superiority of PCV values throughout the experiment
      (p < 0.05). There was a significant reduction (p < 0.05) in L3 recovery in the
      group 1 paddock from day 30 onwards. The use of D. flagrans pellets in
      association with Levamisole Hydrochloride 5% was effective for controlling
      gastrointestinal nematodes.

PMID- 29641797
TI  - Parasites of ornamental fish commercialized in Macapa, Amapa State (Brazil).
AB  - This study investigated the parasites fauna of four freshwater ornamental fish
      species in aquarium shops of Macapa, Amapa State, in addition to survey the
      commercialized fish species and sanitary conditions of aquarium shops. Different
      native and non-native ornamental fish species were found in aquarium shops,
      mainly Poecilidae. We examined 30 specimens of Xiphophorus maculatus, 30 Danio
      rerio, 30 Paracheirodon axelrodi, and 30 Corydoras ephippifer for parasites. Of
      the 120 fish examined, 22.5% were parasitized by one or more species and a total
      of 438 parasites were collected and identified. Parasites such as:
      Ichthyophthirius multifiliis, Monogenea, undermined Digenea metacercariae,
      Acanthostomum sp. metacercariae, Camallanus spp., Bothriocephalus acheilognathi
      and Echinorhynchus sp. infected the hosts examined. Endoparasites in the larval
      stage showed the greatest diversity and Camallanus spp. was found in all hosts
      species examined. Paracheirodon axelrodi (43.3%) was the most parasitized host,
      while C. ephippifer (6.7%) was the least parasitized. Despite the low
      ectoparasites level, six species of endoparasites was observed, demonstrating
      that prophylactic and quarantine procedures were not fully adequate. Therefore,
      failures in prophylactic procedures on any link in the production industry of
      ornamental fish may cause parasite transmission to ornamental fish captured in
      different environments and localities.

PMID- 29641798
TI  - Biological parameters of Amblyomma coelebs Neumann, 1906 (Acari: Ixodidae) under
      experimental conditions.
AB  - One generation of Amblyomma coelebs life cycle under experimental conditions was
      evaluated. Ten tick pairs were allowed to feed on rabbits under laboratory
      conditions (LC), resulting six engorged females with a mean weight of 1,403.9 mg.
      Two females were maintained in a forest reserve under natural conditions (NC),
      and four were maintained in incubators (LC). The engorgement period lasted 10.33
      days. Pre-oviposition periods were 10.75 (NC) and 22 days (LC). The mean egg-mass
      weight was 514.76 mg, and the blood meal conversion index was 36.67% (LC).
      Incubation period under NC and LC were 91 and 56.33 days and hatching rates were
      50% and 28.33%, respectively. Larval engorgement period ranged from 4 to 10 days,
      with average weight of 1.1 mg. Engorged larvae were incubated under NC and LC,
      with a premolt period of 27 to 36 days and molting rate of 7.1% and 28.7%,
      respectively. Nymphal engorgement period ranged from 5 to 7 days, with a mean
      weight of 18.8 mg and a recovery rate of 54.54%. In LC, the ecdysis mean period
      was 24.5 days, and molting rate was 44.44%, resulting in 24 adult A. coelebs. Our
      results show a life cycle of 187.45 (NC) and 149 (LC) days.

PMID- 29641799
TI  - Analysis of the accuracy of different laboratory methods for the diagnosis of
      intestinal parasites from stray and domiciled cats (Felis catus domesticus) in
      Goiania, Goias, Brazil.
AB  - Cats are carriers of zoonotic agents to humans, including intestinal parasites.
      The purpose of this study was to analyze the accuracy of different laboratory
      methods for the diagnosis of intestinal parasites. Fecal samples were processed
      by the Willis, Sheather, Faust and Hoffman-Janer-Pons-Lutz (HJPL) methods.
      Accuracy analysis was performed determining the sensitivity, specificity,
      positive and negative predictive value and Kappa. A total of 149 fecal samples
      were collected, 65 from stray cats and 84 from domiciled cats. The prevalence of
      intestinal parasites in stray cats was 60% while in domiciled cats it was 17%. In
      the analysis of accuracy, the techniques that showed the greatest accuracy for
      Ancylostomids were Willis and Faust, for Cystoisospora spp. Sheather with Faust
      or HPJL, and Toxoplasma gondii/Hammondia hammondi the association between Willis
      and Faust. Therefore, for a reliable evaluation of the prevalence of intestinal
      parasites, at least two different techniques should be used in parasitological
      exams of feces.

PMID- 29641800
TI  - First molecular data for Lernaea cyprinacea (Copepoda: Cyclopoida) infesting
      Odontesthes bonariensis, a commercially important freshwater fish in Argentina.
AB  - Parasitic copepods of the family Lernaeidae are often found infesting freshwater
      fishes worldwide. They cause lernaeosis, a disease that can lead to serious
      pathogenic effects on their fish hosts. The most common lernaeid is the Lernaea
      cyprinacea, which has been widely introduced through importation of tropical
      fishes, e.g. cyprinids. In South America, it is one of the most common parasites
      both in wild and in farmed fish in the central region of Argentina. The
      silverside Odontesthes bonariensis is the most important fish of the sport
      fisheries of Argentina and one of the fish most affected by lernaeosis. Six
      specimens of copepods were collected from 30 specimens of O. bonariensis
      collected in a Pampean shallow lake (33 degrees 25'28"S 62 degrees 53'56"W) of
      Cordoba (Argentina). The 28S rRNA gene of L. cyprinacea was amplified by means of
      PCR to obtain the 28S rDNA sequence. The sequence obtained of this parasite from
      Argentina showed high genetic similarity with those from various geographical
      origins. The present study provided molecular characterization of L. cyprinacea
      in South America for the first time.

PMID- 29641801
TI  - Dynamics of natural infection by Babesia bovis and Babesia bigemina in dairy
      cattle from an enzootic instability area in Northeastern Brazil.
AB  - This study aimed to determine the dynamics of natural infection in the
      transmission of Babesia spp. to cattle in an enzootic instability area in
      Northeastern Brazil. Blood samples were collected from 30 calves located on two
      dairy farms to determine the packed cell volume (PCV) and the timing of the primo
      infection using polymerase chain reaction (PCR) and their association with
      climatic factors and management practices. On Farm A, the determination of primo
      infection was observed on average at 249.4 (+/-24.42) days of age for B. bigemina
      and at 252.6 (+/-17.07) days of age for B. bovis; there was no significant
      difference between the times of infection (P> 0.05). The infection coincided with
      a period of high rainfall in the region. On Farm B, primo-infection infection was
      not observed. There was no infection by Babesia spp. on Farm B due to the
      intensive use of acaricides that led to an absence of ticks. There was no
      significant difference between the average PCV of animals from Farms A and B (P>
      0.05). The management practices on the properties, in addition to the weather
      conditions influenced the exposure of the animals to disease vectors and may have
      contributed to the maintenance of this enzootic area in Northeastern Brazil.

PMID- 29641804
TI  - Tax Collections and Spending as a Potential Measure of Health Policy Association
      With Indoor Tanning, 2011-2016.

PMID- 29641802
TI  - Micromass cultures are effective for differentiation of human amniotic fluid stem
      cells into chondrocytes.
AB  - OBJECTIVES: Articular cartilage is vulnerable to injuries and undergoes an
      irreversible degenerative process. The use of amniotic fluid mesenchymal stromal
      stem cells for the reconstruction of articular cartilage is a promising
      therapeutic alternative. The aim of this study was to investigate the
      chondrogenic potential of amniotic fluid mesenchymal stromal stem cells from
      human amniotic fluid from second trimester pregnant women in a micromass system
      (high-density cell culture) with TGF-beta3 for 21 days. METHODS: Micromass was
      performed using amniotic fluid mesenchymal stromal stem cells previously cultured
      in a monolayer. Chondrocytes from adult human normal cartilage were used as
      controls. After 21 days, chondrogenic potential was determined by measuring the
      expression of genes, such as SOX-9, type II collagen and aggrecan, in newly
      differentiated cells by real-time PCR (qRT-PCR). The production of type II
      collagen protein was observed by western blotting. Immunohistochemistry analysis
      was also performed to detect collagen type II and aggrecan. This study was
      approved by the local ethics committee. RESULTS: SOX-9, aggrecan and type II
      collagen were expressed in newly differentiated chondrocytes. The expression of
      SOX-9 was significantly higher in newly differentiated chondrocytes than in adult
      cartilage. Collagen type II protein was also detected. CONCLUSION: We demonstrate
      that stem cells from human amniotic fluid are a suitable source for
      chondrogenesis when cultured in a micromass system. amniotic fluid mesenchymal
      stromal stem cells are an extremely viable source for clinical applications, and
      our results suggest the possibility of using human amniotic fluid as a source of
      mesenchymal stem cells.

PMID- 29641803
TI  - Difficulties in the diagnosis and treatment of rare diseases according to the
      perceptions of patients, relatives and health care professionals.
AB  - OBJECTIVES: The aim of this study is to present a survey of vulnerabilities and
      to suggest approaches for the treatment of rare diseases according to the
      perceptions of a group of affected individuals, patient association
      representatives and health care professionals. METHODS: The focus group technique
      was used in interviews with patients and primary caregivers, patient support
      groups/non-governmental organizations, primary health care professionals and
      physician specialists. RESULTS: The transcript analysis focused on thematic
      units, which were tailored to each group and allowed comparisons in search of
      concordant views. Unanimity was observed in relation to the physical, emotional
      and social damage to the life standards of the affected individuals and their
      families as a result of illness. The Brazilian health system was unanimously
      classified as inadequate to respond to the needs of patients with rare diseases,
      and this inadequacy led to unpleasant experiences, such as the seemingly endless
      referrals among health services to reach a final diagnosis and develop a
      treatment plan. CONCLUSIONS: The complex set of health system requirements
      necessary to support the care of patients with rare diseases represents an
      obstacle to successfully meeting the needs of patients and their families.
      Therefore, it is important to develop specific public policies to create referral
      services, guarantee access to appropriate therapeutic modalities and incorporate
      technologies that promote research for developing new, affordable therapies.

PMID- 29641805
TI  - A Target to Achieve Zero Preventable Trauma Deaths Through Quality Improvement.

PMID- 29641807
TI  - Thyroid Function Screening in Children With Alopecia Areata.

PMID- 29641806
TI  - Endocrine Therapy-Induced Alopecia in Patients With Breast Cancer.
AB  - Importance: Endocrine therapy-induced alopecia (EIA) has been anecdotally
      reported but not systematically described. Objective: To characterize EIA in
      patients with breast cancer. Design, Setting, and Participants: Retrospective
      cohort study of 112 patients with breast cancer, diagnosed with EIA from January
      1, 2009, to December 31, 2016, the patients were examined at the dermatology
      service in a large tertiary care hospital and comprehensive cancer center. Main
      Outcomes and Measures: The clinical features, alopecia-related quality of life
      (QoL), and response to minoxidil of EIA in patients with breast cancer were
      assessed. Data from the Hairdex Questionnaire was used to assess the impact of
      the alopecia on patients QoL. Higher score indicates lower QoL (0-100 score).
      Efficacy of minoxidil was measured at 3 or 6 months by a single-blinded
      investigator through standardized clinical photographs of the scalp. Results: A
      total of 112 female patients with breast cancer were included (median [range]
      age, 60 [34-90] years). A total of 104 patients (93%) had standardized clinical
      photographs; of these, 59 patients (53%) had trichoscopy images available at
      baseline, and 46 patients (41%) were assessed for response to minoxidil. Alopecia
      was attributed to aromatase inhibitors in 75 patients (67%) and tamoxifen in 37
      (33%). Severity was grade 1 in 96 of 104 patients (92%), and the pattern was
      similar to androgenetic alopecia. The predominant trichoscopic feature at
      baseline was the presence of vellus hairs and intermediate- and thick-diameter
      terminal hair shafts. A negative impact on QoL was reported, with a higher effect
      in the emotion domain according to the Hairdex score (mean [SD], 41.8 [21.3]; P <
      .001). After treatment with topical minoxidil, moderate or significant
      improvement in alopecia was observed in 37 of 46 patients (80%). Conclusions and
      Relevance: Endocrine therapies are associated with a pattern alopecia similar to
      androgenetic-type, consistent with the mechanism of action of causal agents. A
      significant negative impact on QoL was reported by patients, despite mostly mild
      alopecia severity.

PMID- 29641808
TI  - The Dangers of Black Salve: An Unregulated, Commercially Available Caustic Agent.

PMID- 29641809
TI  - Catalyzing Future Drug, Device, and Information Technology Breakthroughs in
      Dermatology: Announcing Advancing Innovation in Dermatology's Accelerator Fund.

PMID- 29641810
TI  - Management of Ventricular Arrhythmias and Sudden Cardiac Death Risk Related to
      Ischemic and Nonischemic Cardiomyopathy.

PMID- 29641811
TI  - Thyroid Function Screening in Children With Alopecia Areata-Reply.

PMID- 29641812
TI  - Minoxidil for Endocrine Therapy-Induced Alopecia in Women With Breast Cancer
      Saint Agatha's Blessing?

PMID- 29641813
TI  - Regionalization, Readmissions, and Repercussions of Major Cancer Surgery.

PMID- 29641814
TI  - Net Neutrality Repeal and the Potential Harm to Medical Education.

PMID- 29641815
TI  - Why Are Legionnaires Disease Diagnoses Becoming More Common in the United States?

PMID- 29641817
TI  - Intertriginous Multiple Reddish-Brown Papulonodules.

PMID- 29641818
TI  - Improving Disclosure of Financial Conflicts of Interest for Research on
      Psychosocial Interventions.

PMID- 29641816
TI  - Longitudinal Associations Among Bullying by Peers, Disordered Eating Behavior,
      and Symptoms of Depression During Adolescence.
AB  - Importance: Bullying by peers has been associated with disordered eating behavior
      and symptoms of depression among adolescents as both an antecedent and an
      outcome. Identification of the temporal pattern of associations among bullying by
      peers, disordered eating behavior, and depression in adolescence is needed for
      the optimal targeting of intervention and prevention. Objective: To assess the
      concurrent and longitudinal associations among bullying by peers, disordered
      eating behavior, and symptoms of depression using a cascade model that controlled
      for within-time and across-time (ie, stability paths) associations while
      examining cross-lag effects. Design, Setting, and Participants: In this 5-year
      longitudinal cohort study, 612 participants of the McMaster Teen Study were
      included. This ongoing Canadian study examines the associations among bullying,
      mental health, and educational outcomes. Data collection began in 2008 when
      students were in grade 5 (10 years of age) and have since been collected
      annually. Data analysis was performed between August 20 and October 18, 2017.
      Exposures: Bullying by peers was assessed in grades 7 to 11 using a composite
      measure of 5 items. Main Outcomes and Measures: Disordered eating behavior was
      assessed in grades 7 to 11 using the Short Screen for Eating Disorders, and
      depressive symptoms were assessed in grades 7 to 11 using the Behavior Assessment
      System for Children-Second Edition. Results: The 612 students included in the
      analytic sample had a mean age (SD) of 13.03 (0.38) years in grade 7; 331 (54.1%)
      were girls and 392 (71.1%) were white. Bullying by peers was concurrently
      associated with disordered eating behavior and depressive symptoms at every time
      point during the 5-year period (r range [SE], 0.15-0.48 [0.04-0.08]; P < .01).
      Disordered eating behavior was associated longitudinally with depressive symptoms
      at every time point (beta range [SE], 0.14-0.19 [0.06-0.08]; P < .02) and
      bullying by peers at 2 time points (beta range [SE], 0.12-0.22 [0.06-0.07]; P <
      .04) in girls and boys. Conclusions and Relevance: Bullying by peers was
      proximally associated with multiple psychopathologic symptoms, whereas symptoms
      of disordered eating behavior were a key risk factor for future depressive
      symptoms and bullying by peers. Interventions aimed at reducing problematic
      eating behavior in adolescents may attenuate the risk of future depressive
      symptoms and relational problems.

PMID- 29641819
TI  - Social Worker-Aided Palliative Care Intervention in High-risk Patients With Heart
      Failure (SWAP-HF): A Pilot Randomized Clinical Trial.
AB  - Importance: Palliative care considerations are typically introduced late in the
      disease trajectory of patients with advanced heart failure (HF), and access to
      specialty-level palliative care may be limited. Objective: To determine if early
      initiation of goals of care conversations by a palliative care-trained social
      worker would improve prognostic understanding, elicit advanced care preferences,
      and influence care plans for high-risk patients discharged after HF
      hospitalization. Design, Setting, and Participants: This prospective, randomized
      clinical trial of a social worker-led palliative care intervention vs usual care
      analyzed patients recently hospitalized for management of acute HF who had risk
      factors for poor prognosis. Analyses were conducted by intention to treat.
      Interventions: Key components of the social worker-led intervention included a
      structured evaluation of prognostic understanding, end-of-life preferences,
      symptom burden, and quality of life with routine review by a palliative care
      physician; communication of this information to treating clinicians; and
      longitudinal follow-up in the ambulatory setting. Main Outcomes and Measures:
      Percentage of patients with physician-level documentation of advanced care
      preferences and the degree of alignment between patient and cardiologist
      expectations of prognosis at 6 months. Results: The study population (N = 50) had
      a mean (SD) age of 72 (11) years and had a mean (SD) left ventricular ejection
      fraction of 0.33 (13). Of 50 patients, 41 (82%) had been hospitalized more than
      once for HF management within 12 months of enrollment. At enrollment, treating
      physicians anticipated death within a year for 32 patients (64%), but 42 patients
      (84%) predicted their life expectancy to be longer than 5 years. At 6 months,
      more patients in the intervention group than in the control group had physician
      level documentation of advanced care preferences in the electronic health record
      (17 [65%] vs 8 [33%]; chi2 = 5.1; P = .02). Surviving patients allocated to
      intervention were also more likely to revise their baseline prognostic assessment
      in a direction consistent with the physician's assessment (15 [94%] vs 4 [26%];
      chi2 = 14.7; P < .001). Among the 31 survivors at 6 months, there was no measured
      difference between groups in depression, anxiety, or quality-of-life scores.
      Conclusions and Relevance: Patients at high risk for mortality from HF frequently
      overestimate their life expectancy. Without an adverse impact on quality of life,
      prognostic understanding and patient-physician communication regarding goals of
      care may be enhanced by a focused, social worker-led palliative care intervention
      that begins in the hospital and continues in the outpatient setting. Trial
      Registration: clinicaltrials.gov Identifier: NCT02805712.

PMID- 29641821
TI  - Geographic Variation in Cardiovascular Disease Burden: Clues and Questions.

PMID- 29641822
TI  - Maturing Methods for Cardiovascular Disease and Stroke Surveillance in the United
      States.

PMID- 29641825
TI  - Lupus-Crying Wolf.

PMID- 29641826
TI  - Hulusi Behcet-A Life of Passion and Endeavor in Dermatology.

PMID- 29641827
TI  - Morgellons Disease-Dredged Up From History and Customized.

PMID- 29641828
TI  - Albert Sezary-The Man, the Cell, and the Syndrome.

PMID- 29641820
TI  - The Burden of Cardiovascular Diseases Among US States, 1990-2016.
AB  - Importance: Cardiovascular disease (CVD) is the leading cause of death in the
      United States, but regional variation within the United States is large.
      Comparable and consistent state-level measures of total CVD burden and risk
      factors have not been produced previously. Objective: To quantify and describe
      levels and trends of lost health due to CVD within the United States from 1990 to
      2016 as well as risk factors driving these changes. Design, Setting, and
      Participants: Using the Global Burden of Disease methodology, cardiovascular
      disease mortality, nonfatal health outcomes, and associated risk factors were
      analyzed by age group, sex, and year from 1990 to 2016 for all residents in the
      United States using standardized approaches for data processing and statistical
      modeling. Burden of disease was estimated for 10 groupings of CVD, and
      comparative risk analysis was performed. Data were analyzed from August 2016 to
      July 2017. Exposures: Residing in the United States. Main Outcomes and Measures:
      Cardiovascular disease disability-adjusted life-years (DALYs). Results: Between
      1990 and 2016, age-standardized CVD DALYs for all states decreased. Several
      states had large rises in their relative rank ordering for total CVD DALYs among
      states, including Arkansas, Oklahoma, Alabama, Kentucky, Missouri, Indiana,
      Kansas, Alaska, and Iowa. The rate of decline varied widely across states, and
      CVD burden increased for a small number of states in the most recent years.
      Cardiovascular disease DALYs remained twice as large among men compared with
      women. Ischemic heart disease was the leading cause of CVD DALYs in all states,
      but the second most common varied by state. Trends were driven by 12 groups of
      risk factors, with the largest attributable CVD burden due to dietary risk
      exposures followed by high systolic blood pressure, high body mass index, high
      total cholesterol level, high fasting plasma glucose level, tobacco smoking, and
      low levels of physical activity. Increases in risk-deleted CVD DALY rates between
      2006 and 2016 in 16 states suggest additional unmeasured risks beyond these
      traditional factors. Conclusions and Relevance: Large disparities in total burden
      of CVD persist between US states despite marked improvements in CVD burden.
      Differences in CVD burden are largely attributable to modifiable risk exposures.

PMID- 29641829
TI  - Theodore Lawless-A Physician-Scientist, Philanthropist, and Champion of the
      African American Community.

PMID- 29641830
TI  - The Vedic View of Vitiligo.

PMID- 29641832
TI  - Stephen Devries, MD: Training Physicians About Nutrition.

PMID- 29641833
TI  - Comparison of Rates and Outcomes of Readmission to Index vs Nonindex Hospitals
      After Major Cancer Surgery.
AB  - Importance: Increasing regionalization of cancer surgery has the inadvertent
      potential to lead to fragmentation of care if readmissions occur at a facility
      other than the index hospital. The magnitude and adverse effects of readmission
      to a facility other than the one where the surgery was performed are unclear.
      Objectives: To assess rates of readmission to nonindex hospitals after major
      cancer surgery and to compare outcomes between index and nonindex hospital
      readmissions. Design, Setting, and Participants: In this multicenter, population
      based, nationally representative study of adult patients undergoing a major
      cancer operation (defined as esophagectomies or gastrectomies, hepaticobiliary
      resections, pancreatectomies, colorectal resections, or cystectomies),
      retrospective analyses were performed using the Nationwide Readmissions Database
      (admissions from January 1 through September 30, 2013). Descriptive analyses were
      performed to determine 90-day readmission characteristics, including timing,
      cost, and outcomes. Adjusting for clustering by facility, the study used
      multivariate logistic regression to identify factors associated with nonindex vs
      index readmissions. The study also used regression models to identify differences
      in mortality, major complications, and subsequent readmissions between the 2
      groups. Data analysis was performed from January 1 through December 31, 2013.
      Exposures: Readmission to index vs nonindex hospitals (defined as any hospital
      other than the hospital where the major cancer operation was performed). Main
      Outcomes and Measures: Proportion of 90-day readmissions and nonindex
      readmissions after major cancer surgery, factors associated with nonindex
      readmissions, and difference between in-hospital mortality, hospital costs, and
      subsequent readmissions for patients admitted to index vs nonindex hospitals.
      Results: A total of 60 970 patients were included in the study (mean [SD] age, 67
      [13] years; 7619 [55.6%] male and 6075 [44.4%] female). The 90-day readmission
      rate was 23.0%. Of the 13 695 first readmissions, 20.1% were to a nonindex
      hospital. Independent factors associated with readmission to a nonindex hospital
      included type of procedure, comorbidities (OR, 1.40; 95% CI, 1.15-1.70), elective
      admission (OR, 1.21; 95% CI, 1.06-1.37), discharge to a nursing facility (OR,
      1.20; 95% CI, 1.07-1.36), and surgery at a teaching hospital (OR, 1.16; 95% CI,
      1.00-1.34) (all P < .05). After risk adjustment, patients readmitted to nonindex
      hospitals had 31.2% higher odds of mortality (odds ratio, 1.31; 95% CI, 1.05
      1.64) and 27.3% higher odds of having a major complication (odds ratio, 1.27; 95%
      CI, 1.14-1.42). Subsequent readmissions and hospital costs were not different
      between the 2 groups. Conclusions and Relevance: Approximately one-fifth of
      readmissions were to a nonindex hospital and were associated with higher
      mortality and morbidity than readmission to index hospitals. Factors that
      influence nonindex readmissions have been identified to target interventions.

PMID- 29641835
TI  - Practice Patterns and Complications of Benign Hysterectomy Following the FDA
      Statement Warning Against the Use of Power Morcellation.
AB  - Importance: In November 2014, the US Food and Drug Administration (FDA) issued a
      black box warning against the use of power morcellation for excision of uterine
      fibroids to decrease the risk of disseminating malignant cells and worsening
      survival outcomes of patients with unexpected malignant neoplasms. After the FDA
      statement was issued, studies showed decreased rates of minimally invasive
      surgery and increased rates of open abdominal hysterectomy. However, there are
      limited and controversial data on the association of these changed rates with 30
      day hysterectomy complications. Objective: To assess changes in the rates of 30
      day major and minor complications of hysterectomy for benign gynecologic
      indications following the FDA-issued statement. Design, Setting, and
      Participants: This retrospective cohort study used the American College of
      Surgeons National Surgical Quality Improvement Program database and included 603
      hospitals participating between January 1, 2013, and December 31, 2015. Thirty
      day posthysterectomy complications were compared before and after the FDA-issued
      warning. Women who underwent hysterectomy for benign gynecologic indications (n =
      75 487), including hysterectomies with indication of uterine fibroids (n = 25
      571), were included. Complication rates and procedure distributions between the
      periods were compared with chi2 tests and multivariable logistic regression
      controlling for patient and operative factors. Main Outcomes and Measures: Major
      and minor 30-day complication rates before (from 2013 through the first quarter
      of 2014) and after (from the fourth quarter of 2014 through 2015) the FDA-issued
      warning. Results: Of 75 487 women (mean [SD] age, 47.8 [10.7] years) who
      underwent hysterectomy for benign gynecologic indications, 32 186 (42.6%) were
      treated before and 43 301 (57.4%) after the FDA-issued warning. Non-Hispanic
      white women comprised most (59.4%) of the total population, followed by African
      American women (15.1%). Overall, major and minor complications remained stable
      before and after the FDA-issued warning. By contrast, among a subset of 25 571
      women (33.9%) who underwent hysterectomy for uterine fibroids, major
      complications significantly increased after the FDA-issued warning from 1.9% to
      2.4% (adjusted odds ratio [OR], 1.23; 95% CI, 1.04-1.47; P = .02), and minor
      complications significantly increased from 2.7% to 3.3% (adjusted OR, 1.21; 95%
      CI, 1.04-1.40; P = .01). In this subgroup, the rate of open abdominal surgery
      increased from 37.2% to 43.0%, and the rate of minimally invasive surgery (total
      laparoscopic hysterectomy, laparoscopic supracervical hysterectomy, and
      laparoscopic-assisted vaginal hysterectomy) decreased from 56.1% to 49.7% (P <
      .001). Conclusions and Relevance: Major and minor 30-day complication rates among
      women undergoing hysterectomy for uterine fibroids increased following the FDA
      issued statement. This increased risk corresponding with a decreased use of
      minimally invasive surgery should be balanced against the potential harms of
      morcellation during a shared decision-making process between clinician and
      patient. Regulatory bodies and medical societies should consider these findings
      when issuing relevant communications.

PMID- 29641834
TI  - Pretreatment Rostral Anterior Cingulate Cortex Theta Activity in Relation to
      Symptom Improvement in Depression: A Randomized Clinical Trial.
AB  - Importance: Major depressive disorder (MDD) remains challenging to treat.
      Although several clinical and demographic variables have been found to predict
      poor antidepressant response, these markers have not been robustly replicated to
      warrant implementation in clinical care. Increased pretreatment rostral anterior
      cingulate cortex (rACC) theta activity has been linked to better antidepressant
      outcomes. However, no prior study has evaluated whether this marker has
      incremental predictive validity over clinical and demographic measures.
      Objective: To determine whether increased pretreatment rACC theta activity would
      predict symptom improvement regardless of randomization arm. Design, Setting, and
      Participants: A multicenter randomized clinical trial enrolled outpatients
      without psychosis and with chronic or recurrent MDD between July 29, 2011, and
      December 15, 2015 (Establishing Moderators and Biosignatures of Antidepressant
      Response for Clinical Care [EMBARC]). Patients were consecutively recruited from
      4 university hospitals: 634 patients were screened, 296 were randomized to
      receive sertraline hydrochloride or placebo, 266 had electroencephalographic
      (EEG) recordings, and 248 had usable EEG data. Resting EEG data were recorded at
      baseline and 1 week after trial onset, and rACC theta activity was extracted
      using source localization. Intent-to-treat analysis was conducted. Data analysis
      was performed from October 7, 2016, to January 19, 2018. Interventions: An 8-week
      course of sertraline or placebo. Main Outcomes and Measures: The 17-item Hamilton
      Rating Scale for Depression score (assessed at baseline and weeks 1, 2, 3, 4, 6,
      and 8). Results: The 248 participants (160 [64.5%] women, 88 [35.5%] men) with
      usable EEG data had a mean (SD) age of 36.75 (13.15) years. Higher rACC theta
      activity at both baseline (b = -1.05; 95% CI, -1.77 to -0.34; P = .004) and week
      1 (b = -0.83; 95% CI, -1.60 to -0.06; P < .04) predicted greater depressive
      symptom improvement, even when controlling for clinical and demographic variables
      previously linked with treatment outcome. These effects were not moderated by
      treatment arm. The rACC theta marker, in combination with clinical and
      demographic variables, accounted for an estimated 39.6% of the variance in
      symptom change (with 8.5% of the variance uniquely attributable to the rACC theta
      marker). Conclusions and Relevance: Increased pretreatment rACC theta activity
      represents a nonspecific prognostic marker of treatment outcome. This is the
      first study to date to demonstrate that rACC theta activity has incremental
      predictive validity. Trial Registration: clinicaltrials.gov Identifier:
      NCT01407094.

PMID- 29641837
TI  - Association of changes in work shifts and shift intensity with change in fatigue
      and disturbed sleep: a within-subject study.
AB  - Objectives The aim of this study was to examine whether changes in work shifts
      and shift intensity are related to changes in difficulties to fall asleep,
      fatigue, and sleep length. Methods Questionnaire responses of hospital employees
      (N=7727, 93% women) in 2008, 2012, 2014 and 2015 were linked to daily-based
      records of working hours during three months preceding each survey. We used
      conditional logistic regression and longitudinal fixed-effects analyses to
      investigate odds ratios (OR) and 95% confidence intervals (CI) for each 25%
      within-individual change in the proportion of working hour characteristics in
      relation to changes in fatigue, difficulties to fall asleep, and 24-hour sleep
      length. Results Change in night but not in morning or evening shifts was
      associated with parallel changes in odds for longer sleep length (OR 1.45, 95% CI
      1.28-1.64) and fatigue during free days (OR 1.38, 95% CI 1.16-1.64). Similarly,
      short shift intervals and having >2 but not >4 consecutive night shifts were
      associated with increased odds of fatigue during work and difficulties to fall
      asleep (OR 1.42, 95% CI 1.19-1.72 and OR 1.10, 95% CI 1.05-1.19, respectively).
      Among workers aged >=50 years, the associations were the strongest between night
      shifts and longer sleep (OR 2.24, 95% CI 1.52-3.81) and between higher proportion
      of short shift intervals and fatigue during free days (OR 1.68, 95% CI 1.10
      2.54). Conclusions Among shift workers with fatigue or sleep problems, decreasing
      the proportion of night shifts and quick returns and giving preference to quickly
      forward-rotating shift systems may reduce fatigue.

PMID- 29641836
TI  - Association of Cardiomyopathy With MYBPC3 D389V and MYBPC3Delta25bpIntronic
      Deletion in South Asian Descendants.
AB  - Importance: The genetic variant MYBPC3Delta25bp occurs in 4% of South Asian
      descendants, with an estimated 100 million carriers worldwide. MYBPC3 Delta25bp
      has been linked to cardiomyopathy and heart failure. However, the high prevalence
      of MYBPC3Delta25bp suggests that other stressors act in concert with
      MYBPC3Delta25bp. Objective: To determine whether there are additional genetic
      factors that contribute to the cardiomyopathic expression of MYBPC3Delta25bp.
      Design, Setting, andParticipants: South Asian individuals living in the United
      States were screened for MYBPC3Delta25bp, and a subgroup was clinically evaluated
      using electrocardiograms and echocardiograms at Loyola University, Chicago,
      Illinois, between January 2015 and July 2016. Main Outcomes and Measures: Next
      generation sequencing of 174 cardiovascular disease genes was applied to identify
      additional modifying gene mutations and correlate genotype-phenotype parameters.
      Cardiomyocytes derived from human-induced pluripotent stem cells were established
      and examined to assess the role of MYBPC3Delta25bp. Results: In this genotype
      phenotype study, individuals of South Asian descent living in the United States
      from both sexes (36.23% female) with a mean population age of 48.92 years (range,
      18-84 years) were recruited. Genetic screening of 2401 US South Asian individuals
      found an MYBPC3Delta25bpcarrier frequency of 6%. A higher frequency of missense
      TTN variation was found in MYBPC3Delta25bp carriers compared with noncarriers,
      identifying distinct genetic backgrounds within the MYBPC3Delta25bp carrier
      group. Strikingly, 9.6% of MYBPC3Delta25bp carriers also had a novel MYBPC3
      variant, D389V. Family studies documented D389V was in tandem on the same allele
      as MYBPC3Delta25bp, and D389V was only seen in the presence of MYBPC3Delta25bp.
      In contrast to MYBPC3Delta25bp, MYBPC3Delta25bp/D389V was associated with
      hyperdynamic left ventricular performance (mean [SEM] left ventricular ejection
      fraction, 66.7 [0.7%]; left ventricular fractional shortening, 36.6 [0.6%]; P <
      .03) and stem cell-derived cardiomyocytes exhibited cellular hypertrophy with
      abnormal Ca2+ transients. Conclusions and Relevance: MYBPC3Delta25bp/D389V is
      associated with hyperdynamic features, which are an early finding in hypertrophic
      cardiomyopathy and thought to reflect an unfavorable energetic state. These
      findings support that a subset of MYBPC3Delta25bp carriers, those with D389V,
      account for the increased risk attributed to MYBPC3Delta25bp.

PMID- 29641839
TI  - Impact of limb weakness on extubation failure after planned extubation in medical
      patients.
AB  - BACKGROUND AND OBJECTIVE: Limb muscle weakness is associated with difficult
      weaning. However, there are limited data on extubation failure. The objective of
      this cohort study was to evaluate the association between limb muscle weakness
      according to the Medical Research Council (MRC) scale and extubation failure
      rates among patients in a medical intensive care unit (ICU). METHODS: All
      consecutive medical ICU patients who were mechanically ventilated for more than
      24 h and who were weaned according to protocol were prospectively registered, and
      limb muscle weakness was assessed using the MRC scale on the day of planned
      extubation. Association of limb muscle weakness with extubation failure within 48
      h following planned extubation was evaluated with logistic regression analysis.
      RESULTS: Over the study period, 377 consecutive patients underwent planned
      extubation through a standardized weaning process. Extubation failure occurred in
      106 (28.1%) patients. Median scores on the MRC scale for four limbs were lower in
      patients with extubation failure (14, interquartile range (IQR) 12-16) than in
      patients without extubation failure (16, IQR 12-18; P = 0.024). In addition,
      extubation failure rates decreased significantly with increasing quartiles of MRC
      scores (P for trend <0.001). In multivariable analysis, MRC scores <=10 points
      were independently associated with extubation failure within 48 h (adjusted OR
      2.131, 95% CI: 1.071-4.240, P = 0.031). CONCLUSION: Limb muscle weakness assessed
      on the day of extubation was found to be independently associated with higher
      extubation failure rates within 48 h following planned extubation in medical
      patients.

PMID- 29641838
TI  - Drug-resistant tuberculosis: An update on disease burden, diagnosis and
      treatment.
AB  - The emergence of antimicrobial resistance against Mycobacterium tuberculosis, the
      leading cause of mortality due to a single microbial pathogen worldwide,
      represents a growing threat to public health and economic growth. The global
      burden of multidrug-resistant tuberculosis (MDR-TB) has recently increased by an
      annual rate of more than 20%. According to the World Health Organization
      approximately only half of all patients treated for MDR-TB achieved a successful
      outcome. For many years, patients with drug-resistant tuberculosis (TB) have
      received standardized treatment regimens, thereby accelerating the development of
      MDR-TB through drug-specific resistance amplification. Comprehensive drug
      susceptibility testing (phenotypic and/or genotypic) is necessary to inform
      physicians about the best drugs to treat individual patients with tailor-made
      treatment regimens. Phenotypic drug resistance can now often, but with variable
      sensitivity, be predicted by molecular drug susceptibility testing based on whole
      genome sequencing, which in the future could become an affordable method for the
      guidance of treatment decisions, especially in high-burden/resource-limited
      settings. More recently, MDR-TB treatment outcomes have dramatically improved
      with the use of bedaquiline-based regimens. Ongoing clinical trials with novel
      and repurposed drugs will potentially further improve cure-rates, and may
      substantially decrease the duration of MDR-TB treatment necessary to achieve
      relapse-free cure.

PMID- 29641840
TI  - Year in review 2017: Interventional pulmonology, lung cancer, pleural disease and
      respiratory infections.

PMID- 29641841
TI  - Consensus minimum data set for lung cancer multidisciplinary teams: Results of a
      Delphi process.
AB  - BACKGROUND AND OBJECTIVE: While multidisciplinary team (MDT) care in lung cancer
      is widely practiced, there are few guidelines for MDT on best data collection
      strategies. MDT meetings need ready access to information for the provision of
      optimal treatment recommendations (the primary purpose of the meeting), audit of
      team performance and benchmarking. This study aimed to develop a practical data
      set designed for these goals through a recognized consensus process with health
      professionals who participate in formal MDT settings. METHODS: A modified Delphi
      process with three iterations (two surveys and one consensus conference) was
      carried out involving over 100 Australian lung cancer MDT health professionals.
      RESULTS: In total, 122 lung cancer MDT health professionals responded to the
      Round 1 survey from over 350 invitees. Of the 122, 98 were available for
      invitation to Round 2. Of 98, 52 (53%) invitees responded to the Round 2 survey.
      After two rounds, 51 data elements across 8 domains (patient demographics, risk
      factors, biopsy data, staging, timeliness, treatment, follow-up and patient
      selection) achieved consensus, defined as 80% agreement. For Round 3, 33 MDT lead
      clinicians were invited to participate in a consensus conference. Of 33, 14 (42%)
      invitees distilled the 47 data elements into 23 elements across 8 domains to
      address the study objectives. CONCLUSION: A practical data set for lung cancer
      MDT to use for optimal treatment recommendations and to evaluate team performance
      was developed through recognized consensus methodology. Access to streamlined,
      relevant and feasible data collection strategies may improve MDT decision-making,
      audit of team performance and facilitate benchmarking.

PMID- 29641842
TI  - Difficulties of predicting the timing, size and severity of influenza seasons.

PMID- 29641843
TI  - International continence society best practice statement for use of sacral
      neuromodulation.

PMID- 29641844
TI  - 2018 Australian Rheumatology Association Annual Scientific Meeting with the
      Rheumatology Health Professionals Association, 5-8 May 2018, Melbourne Convention
      and Exhibition Centre, Melbourne, Australia.

PMID- 29641845
TI  - Increased risk of acute coronary syndrome in patients with bronchiectasis: A
      population-based cohort study.
AB  - BACKGROUND AND OBJECTIVE: There are few studies on the relationship between
      bronchiectasis and acute coronary syndrome (ACS). We conducted a population-based
      cohort study to assess whether bronchiectasis was associated with an increased
      risk of ACS. METHODS: We identified 3521 patients diagnosed with bronchiectasis
      between 2000 and 2010 (bronchiectasis cohort) and frequency matched them with 14
      084 randomly selected people without bronchiectasis from the general population
      (comparison cohort) according to sex, age and index year using the Longitudinal
      Health Insurance Database. Both cohorts were followed until the end of 2010 to
      determine the ACS incidence. Hazard ratios of ACS were measured. RESULTS: Based
      on 17 340 person-years for bronchiectasis patients and 73 639 person-years for
      individuals without bronchiectasis, the overall ACS risk was 40% higher in the
      bronchiectasis cohort (adjusted hazard ratio (HR) = 1.40; 95% CI: 1.20-1.62).
      Compared with those in the comparison cohort with one respiratory infection
      related emergency room (ER) visit per year, the ACS risk was 5.46-fold greater in
      bronchiectasis patients with three or more ER visits per year (adjusted HR =
      5.46, 95% CI: 4.29-6.96). Patients with bronchiectasis and three or more
      respiratory infection-related hospitalizations per year had an 8.15-fold higher
      ACS risk (adjusted HR = 8.15, 95% CI: 6.27-10.61). CONCLUSION: Bronchiectasis
      patients, particularly those experiencing frequent exacerbations with three or
      more ER visits and consequent hospitalization per year, are at an increased ACS
      risk.

PMID- 29641846
TI  - International Continence Society best practice statement for use of sacral
      neuromodulation.
AB  - AIMS: Sacral neuromodulation (SNM) is an accepted therapy for a variety of
      conditions. However, despite over 20 years of experience, it remains a
      specialized procedure with a number of subtleties. Here we present the
      recommendations issued from the International Continence Society (ICS) SNM
      Consensus Panel. METHODS: Under the auspices of the ICS, eight urologists, three
      colorectal surgeons and two urogynecologists, covering a wide breadth of
      geographic and specialty interest representation, met in January 2017 to discuss
      best practices for neuromodulation. Suggestions for statements were submitted in
      advance and specific topics were assigned to committee members, who prepared and
      presented supporting data to the group, at which time each topic was discussed in
      depth. Best practice statements were formulated based on available data. This
      document was then circulated to multiple external reviewers after which final
      edits were made and approved by the group. RESULTS: The present recommendations,
      based on the most relevant data available in the literature, as well as expert
      opinion, address a variety of specific and at times problematic issues associated
      with SNM. These include the use of SNM for a variety of underlying conditions,
      need for pre-procedural testing, use of staged versus single-stage procedures,
      screening for success during the trial phase, ideal anesthesia, device
      implantation, post-procedural management, trouble-shooting loss of device
      function, and future directions for research. CONCLUSIONS: These guidelines
      undoubtedly constitute a reference document, which will help urologists,
      gynecologists, and colorectal surgeons optimize their use of SNM for refractory
      urinary urgency and frequency, UUI, NOR, and FI.

PMID- 29641847
TI  - Oesophageal diameter is associated with severity but not progression of systemic
      sclerosis-associated interstitial lung disease.
AB  - BACKGROUND AND OBJECTIVE: It is unknown whether oesophageal disease is associated
      with systemic sclerosis-associated interstitial lung disease (SSc-ILD) severity,
      progression or mortality. METHODS: High-resolution computed tomography (HRCT)
      scans from 145 SSc-ILD patients were scored for fibrosis score, oesophageal
      diameter and presence of hiatal hernia. Fibrosis asymmetry was calculated as:
      (most affected side - least affected side)/(most affected side + least affected
      side). Mixed effects models were used for repeated measures analyses. RESULTS:
      Mean fibrosis score was 8.6%, and most patients had mild-to-moderate
      physiological impairment. Every 1 cm increase in oesophageal diameter was
      associated with 1.8% higher fibrosis score and 5.5% lower forced vital capacity
      (FVC; P <= 0.001 for unadjusted and adjusted analyses). Patients with hiatal
      hernia had 3.9% higher fibrosis score, with persistent differences on adjusted
      analysis (P = 0.001). Oesophageal diameter predicted worsening fibrosis score
      over the subsequent year (P = 0.02), but not when adjusting for baseline fibrosis
      score (P = 0.16). Oesophageal diameter was independently associated with
      mortality (P = 0.001). Oesophageal diameter was not associated with asymmetric
      disease or radiological features of gross aspiration. CONCLUSION: Oesophageal
      diameter and hiatal hernia are independently associated with SSc-ILD severity and
      mortality, but not with ILD progression or asymmetric disease. Oesophageal
      disease is unlikely to be a significant driver of ILD progression in SSc.

PMID- 29641848
TI  - Laparoscopic-endoscopic rendezvous versus preoperative endoscopic sphincterotomy
      in people undergoing laparoscopic cholecystectomy for stones in the gallbladder
      and bile duct.
AB  - BACKGROUND: The management of gallbladder stones (lithiasis) concomitant with
      bile duct stones is controversial. The more frequent approach is a two-stage
      procedure, with endoscopic sphincterotomy and stone removal from the bile duct
      followed by laparoscopic cholecystectomy. The laparoscopic-endoscopic rendezvous
      combines the two techniques in a single-stage operation. OBJECTIVES: To compare
      the benefits and harms of endoscopic sphincterotomy and stone removal followed by
      laparoscopic cholecystectomy (the single-stage rendezvous technique) versus
      preoperative endoscopic sphincterotomy followed by laparoscopic cholecystectomy
      (two stages) in people with gallbladder and common bile duct stones. SEARCH
      METHODS: We searched The Cochrane Hepato-Biliary Group Controlled Trials
      Register, CENTRAL, MEDLINE Ovid, Embase Ovid, Science Citation Index Expanded Web
      of Science, and two trials registers (February 2017). SELECTION CRITERIA: We
      included randomised clinical trials that enrolled people with concomitant
      gallbladder and common bile duct stones, regardless of clinical status or
      diagnostic work-up, and compared laparoscopic-endoscopic rendezvous versus
      preoperative endoscopic sphincterotomy procedures in people undergoing
      laparoscopic cholecystectomy. We excluded other endoscopic or surgical methods of
      intraoperative clearance of the bile duct, e.g. non-aided intraoperative
      endoscopic retrograde cholangiopancreatography or laparoscopic
      choledocholithotomy (surgical incision of the common bile duct for removal of
      bile duct stones). DATA COLLECTION AND ANALYSIS: We used standard methodological
      procedures recommended by Cochrane. MAIN RESULTS: We included five randomised
      clinical trials with 517 participants (257 underwent a laparoscopic-endoscopic
      rendezvous technique versus 260 underwent a sequential approach), which fulfilled
      our inclusion criteria and provided data for analysis. Trial participants were
      scheduled for laparoscopic cholecystectomy because of suspected cholecysto
      choledocholithiasis. Male/female ratio was 0.7; age of men and women ranged from
      21 years to 87 years. The run-in and follow-up periods of the trials ranged from
      32 months to 84 months. Overall, the five trials were judged at high risk of
      bias. Athough all trials measured mortality, there was just one death reported in
      one trial, in the laparoscopic-endoscopic rendezvous group (low-quality
      evidence). The overall morbidity (surgical morbidity plus general morbidity) may
      be lower with laparoscopic rendezvous (RR 0.59, 95% CI 0.29 to 1.20; participants
      = 434, trials = 4; I2 = 28%; low-quality evidence); the effect was a little more
      certain when a fixed-effect model was used (RR 0.56, 95% CI 0.32 to 0.99). There
      was insufficient evidence to determine the effects of the two approaches on the
      failure of primary clearance of the bile duct (RR 0.55, 95% CI 0.22 to 1.38;
      participants = 517; trials = 5; I2 = 58%; very low-quality evidence). The effects
      of either approach on clinical post-operative pancreatitis were unclear (RR 0.29,
      95% CI 0.07 to 1.12; participants = 517, trials = 5; I2 = 24%; low-quality
      evidence). Hospital stay appeared to be lower in the laparoscopic-endoscopic
      rendezvous group by about three days (95% CI 3.51 to 2.50 days shorter; 515
      participants in five trials; low-quality evidence). There was very low-quality
      evidence that suggested longer operative time with laparoscopic-endoscopic
      rendezvous (MD 34.07 minutes, 95% CI 11.41 to 56.74; participants = 313; trials =
      3; I2 = 93%). The Trial Sequential Analyses of operating time and the length of
      hospital stay indicated that all the trials crossed the conventional boundaries,
      suggesting that the sample sizes were adequate, with a low risk of random error.
      AUTHORS' CONCLUSIONS: There was insufficient evidence to determine the effects of
      the laparoscopic-endoscopic rendezvous versus preoperative endoscopic
      sphincterotomy techniques in people undergoing laparoscopic cholecystectomy on
      mortality and morbidity. The laparoscopic-endoscopic rendezvous procedure may
      lead to longer operating times, but it may reduce the length of the hospital stay
      when compared with preoperative endoscopic sphincterotomy followed by
      laparoscopic cholecystectomy. However, no firm conclusions could be drawn because
      the quality of evidence was low or very low. If confirmed by future trials, these
      data might re-design the scenario of treatment of this condition, albeit
      requiring greater organisational effort. Future trials should also address issues
      such as quality of life and cost analysis.

PMID- 29641849
TI  - ?
AB  - No Abstract available.

PMID- 29641850
TI  - [Functionality and stability of the treatment of Weber B ankle fractures with
      syndesmotic injury depending on the placement level of the screw (2.0 versus 3.5
      cm)].
AB  - BACKGROUND: Ankle fractures are one of the most frequent lesions of the
      musculoskeletal system; there are studies that report an increase in the
      incidence of these fractures starting in the 1970s, associated with the increased
      media outreach of sporting activities. Supra- and transyndesmal fractures often
      lead to injury of the syndesmosis, which, if not treated properly, will leave
      joint instability. The most common treatment is the placement of a transyndesmal
      screw; there is controversy on the height in which it should be located with
      regard to the distal tibial joint line. MATERIAL AND METHOD: A descriptive,
      observational, retrospective and transversal study with clinical and radiographic
      records of patients operated on bimalleolar fractures; they were divided into two
      groups: those with the transyndesmal screw at 2 or 2.5 cm and those with the
      screw at 3.5 cm or more proximal. There was a total of 34 cases (group A: 16
      patients; group B: 18), 22 male and 12 female, aged between 19 and 45 years.
      RESULTS: We applied the Olerud-Molander ankle score for the clinical evaluation
      and measured the radiographic medial space of the ankle to consider the degree of
      reduction. The results in both groups were compared. DISCUSSION: The location of
      the screw at 2.0 cm presented a percentage of 75% of joint stability and 25% of
      joint instability, the joint functionality was relatively smaller in comparison
      to the placement of the screw at 3.5 cm, with which we achieved a joint stability
      of 83.3% and 16.3% of joint instability.

PMID- 29641851
TI  - [Bilateral total knee replacement].
AB  - : Bilateral osteoarthrosis of the knee is very frequent and disabling; the
      treatment in severe cases is joint replacement. Bilateral condition and severe
      knee pain are common and the definitive treatment can be performed on both.
      MATERIAL AND METHODS: We reviewed the records of the first patients undergoing
      bilateral total knee replacement by our surgical group, between 1993-1998.
      RESULTS: The procedure was performed on 56 patients (112 knees) with degenerative
      joint disease; their age range was 60 to 82 years. The knee replacements were
      done either simultaneously, consecutively, or via two unique surgeries. The
      outcomes of each method were analyzed to assess its advantages and disadvantages.
      DISCUSSION: Based upon the results of the study, we find that total knee
      replacements done consecutively provide the best results for patients suffering
      from articular degeneration.

PMID- 29641852
TI  - [Epidemiological profile of admissions to the hip and pelvic surgery module in a
      general hospital].
AB  - BACKGROUND: The present study was carried out in order to know, evaluate and
      classify hip fractures treated by the orthopedic service of a general hospital.
      MATERIAL AND METHODS: Retrospective, cross-sectional and descriptive study based
      on the files of the hip and pelvic surgery module of a general hospital in the
      period from July 2009 to December 2016. RESULTS: We included a total of 1,545
      patients aged between 14 and 107 years; the affected side, the reason for
      admission, their previous underlying pathologies, the type of fracture, the type
      of treatment given and the end result were analyzed for each patient. Statistical
      analysis was performed with the program SPSS version 18. Due to the relevance of
      the topic, the causes of the registered deaths were examined (n = 58); in
      relation to the data gathered, 2 and binary logistic regression were obtained.
      CONCLUSIONS: Hip fractures are still an undervalued subject with great economic
      and social impact; knowing the most frequent fracture type as well as the
      population most affected will help to establish effective preventive measures to
      decrease the morbidity and mortality of this disease in a general hospital.

PMID- 29641853
TI  - [Minimally invasive reconstruction of the posterolateral corner with simultaneous
      replacement of the anterior cruciate ligament for complex knee ligament
      injuries].
AB  - OBJECTIVE: To evaluate and describe the results of a simultaneous reconstruction
      with minimally invasive technique of the posterolateral complex (PLC) and the
      anterior cruciate ligament (ACL). MATERIAL AND METHODS: ACL and PLC
      reconstruction was performed in seven patients using the technique described, in
      the period from March to November 2012. All patients were evaluated at six months
      after the procedure using IKDC and IKSS subjective tests. Their return to work
      activities and their level of satisfaction were assessed. RESULTS: Six male and
      one female patients ranging in age between 26 and 46 years were evaluated. The
      injuries were mostly caused by sports related accidents. All patients were
      economically active and required an average period of three months of disability.
      The assessment and outcomes at six months, according to the IKDC scale, were: one
      patient with IKDC A, four with IKDC B, one patient with C, and one with D. In the
      subjective scale IKSS, 80% averaged a knee stability of over 90 points, a patient
      had a 100-point scale and another, of 70 points.

PMID- 29641854
TI  - [Comparison of the clinical response to the application of Hylan G-F 20 and
      collagen-PVP in patients with knee osteoarthritis].
AB  - BACKGROUND: Knee osteoarthritis is a joint disease characterized by degeneration,
      loss of cartilage and subchondral bone alteration associated with changes in the
      soft tissues. In a sample of 2,500 individuals, the prevalence of osteoarthritis
      was found in 2.3% (IC 95% 1.7 a 2.9) in adults; it represents the second cause of
      consultation in our hospital. MATERIAL AND METHODS: Two groups of patients were
      studied: the first included 70 patients who received hylan G-F 20 in three
      infiltrations; the other group, of 40 patients, received collagen-PVP in four
      applications. A subjective questionnaire based on the WOMAC evaluation was
      applied, with which we could assess pain, stiffness and functional capacity
      before and after the application. RESULTS: Both hylan G-F 20 and collagen-PVP
      improved the quality of life of our patients by reducing symptoms such as pain,
      stiffness and functional limitation, collagen being more efficient for reducing
      pain and hylan G-F 20 for reducing stiffness and functional limitation.
      CONCLUSIONS: Both treatments were safe and effective; they can be used in our
      institute as a conservative treatment to decrease hospitalizations for pain
      management.

PMID- 29641855
TI  - [Psychological evaluation in patients treated with external fixator].
AB  - OBJECTIVE: To establish whether complications in treatment, readmissions and
      reinterventions are related to psychological disturbances. To determine if the
      type, age and time of use are related to psychological aspects. MATERIAL AND
      METHODS: Retrospective, observational and transversal study in patients treated
      with external fixator in the period from 2005 to 2010. We used clinical records,
      2 statistical tests and Students t-test with the IBM SPSS Statistics program,
      version 24. RESULTS: Circular fixator: we observed a significant p of 0.024 in
      the relations between age and psychological alterations. Regarding the
      complications and the psychological alterations, we obtained a significant p
      0.048. Monoplanar fixator: the difference was significant of 0.038 on the
      relation between readmissions and psychological alterations. DISCUSSION: There
      are psychological disturbances in patients and families that may interfere with
      the treatment and complications. The literature showed that if there are
      alterations in the initial questionnaire, they will remain equal and generate
      increased aggressiveness; if there were no initial alterations, there will be no
      changes. We observed less psychological effects in older patients (13-16 years)
      and greater anxiety in patients in the medium range (10-12 years), as well as in
      patients with residual deformities. CONCLUSIONS: The psychological intervention
      is important in the pre-, trans- and postsurgical time. Patients of medium age,
      which corresponds to preteens, presented more psychological disturbances;
      therefore, it is recommended to avoid the use of external fixators in this age
      range.

PMID- 29641856
TI  - [How to select a prosthesis for a primary hip replacement? Minimum acceptable
      survival: results of a consensus of experts].
AB  - BACKGROUND: One of the most critical points in the planning of hip replacement
      surgeries is the selection of the implant, since its survival significantly
      impacts the patients health. However, the ideal survival time that an implant
      must prove to be selected has not been defined. The objective of this consensus
      is to define minimum performance standards for the selection of conventional
      primary hip replacement prosthesis. MATERIAL AND METHODS: The consensus was
      carried out using the methodology of nominal group. This included: 1. A review of
      the available evidence and the issues to be evaluated, 2. Meeting for the vote
      and discussion, 3. Quantitative statistical analysis with median (M) and
      interquartile range (IQR) and qualitative one with proportions of the results to
      generate recommendations. RESULTS: The primary source of information for
      prosthesis selection (M: 8; IQR: 7-9), choice in the event of conflicting
      evidence (M: 8; IQR: 7-9), or limited evidence in the literature (M: 7; IQR: 4.75
      825) should be national registries. The minimum acceptable follow-up is 10 years
      (M: 9; IQR: 8-9) and the minimum acceptable survival is 90% at 10 years (M: 8;
      IQR: 5-8.5). DISCUSSION: According to these results, the consensus of experts
      proposed that the selection of the implant for conventional primary hip
      replacement must be based on the information published in the national registries
      and that the prosthesis must have a minimum follow-up of 10 years and show a
      minimum survival of 90%.

PMID- 29641857
TI  - [Total shoulder arthroplasty under monitoring of cerebral perfusion. Report of
      the first case in Mexico].
AB  - INTRODUCTION: The maintenance of cerebral perfusion during shoulder surgery
      performed in the beach chair position is controversial. The aim of this report is
      to present the first case in Mexico of a total shoulder arthroplasty performed
      with interscalene block and monitoring of the cerebral oxygen saturation. This
      monitoring was described in 1977, but only until the last decade has it reached
      relevance from the clinical point of view. CLINICAL CASE: We present an 84-year
      old patient scheduled for total shoulder arthroplasty in beach chair position
      under regional anesthesia (ultrasound-guided interscalene block) in which the
      regional oxygen saturation (CrSO2) was monitored. DISCUSSION: Monitoring of
      cerebral oximetry is a suitable tool that allows us to have a continuous
      assessment throughout the transanesthetic, so we can make decisions more
      expeditiously. On this basis, we believe that this type of monitoring should be
      fundamental in patients placed in a beach chair position, as well as
      predominantly use regional anesthesia. In cases where it cannot be used, this
      monitor is absolutely essential.

PMID- 29641858
TI  - [Intra-articular migration of a tibial bone block after an anterior cruciate
      ligament reconstruction using a bone-tendon-bone graft].
AB  - We report the case of a patient that presented an intra-articular protrusion of
      the tibial bone block after an arthroscopically-assisted ACL reconstruction using
      a bone-patellar tendon-bone graft. The divergence between the tunnel and the
      screw was thought to be the reason of the migration. There are several animal
      model studies that evidence a relationship between the decreased fixation of the
      graft and the tunnel-screw divergence. To the best of our knowledge, this is the
      first report of this complication.

PMID- 29641859
TI  - [Unusual presentation of pigmented villonodular synovitis of the hip joint: case
      report and review of the literature].
AB  - INTRODUCTION: Pigmented villonodular synovitis (PVNS) is a rare clinical entity
      with higher incidence in women (3:1) and an age of presentation between 20 and 40
      years. The hip is a rare site of appearance, being involved in only 15% of all
      cases. CASE REPORT: 47-year-old male with 10 years of evolution characterized by
      a limited range of motion, pain associated with an increase in volume and
      shortening of the pelvic limb. Imaging studies showed destruction of the hip
      joint and extension to the pelvis. The histopathology report described pigmented
      villonodular synovitis. His final treatment was left hemipelvectomy. DISCUSSION:
      The presentation of the diffuse pigmented villonodular synovitis of the hip has a
      lower incidence and a locally aggressive behavior. It is necessary to consider
      differential diagnoses that include malignant neoplasms. The standard treatment
      is surgical.

PMID- 29641860
TI  - A new technique of pedicle screw placement with the use of sequential multilevel
      navigation templates based on patient-specific 3D CT reconstruction model:
      applicability in spine deformity.
AB  - INTRODUCTION: The technique of placement of pedicle screws has gradually
      improved, but even misplacement observed in 1.2 to 20% of cases, have appeared
      techniques fluoroscopic, tomographic and electromagnetic navigation, which led it
      to 1.3 to 4.3%, but nevertheless they are expensive and complex technologies.
      Present technique pedicle screw placement by using templates with a modification
      in the art, performing tomography and reconstruction in the same surgical
      position and with the templates of 3 or more levels. METHODS: Five cases of
      idiopathic scoliosis were performed, with correction and instrumentation with
      pedicular screws, where a three-dimensional model of the spine was performed with
      a tomography in a surgical position, whose images were exported to a 3D printer
      to reconstruct the desired trajectory of the screws in a template using cylinders
      resting on the inverse surface of the vertebrae. The direction of the screw was
      planned in the center of the pedicle and parallel to the upper platform of the
      vertebra. Each template was of several levels and transoperative X-rays were not
      used. RESULTS: Under electrophysiologic monitoring transoperative "red alerts"
      were not reported, the placement of the screws in postoperative CT scan was
      evaluated, showing a standard deviation in placement of 1.9 and 2.2 mm on the
      right and left respectively pedicles, with respect to their planning. DISCUSSION:
      This technique is simple and safe, besides not requiring great technology, its
      use is suggested in beginner spine surgeons and in severe deformities, it can be
      performed in any hospital where spinal surgery is performed.

PMID- 29641861
TI  - [Multidisciplinary meeting on application techniques for restitution of synovial
      fluid in patients with knee arthritis: update].
AB  - In the degradation of articular cartilage, functional limitation and pain
      cardinal signs of osteoarthritis underlies, as a central factor, the quantitative
      and qualitative alteration of hyaluronic acid, the main component of synovial
      fluid and cartilage, in a pathophysiological process influenced by a wide variety
      of risk factors whose impact complicates the disease and radically reduces the
      quality of life of the patient. Conventional pharmacological management for
      osteoarthritis is often insufficient. Fortunately, in our days, there are
      viscosupplements capable of improving, replacing and promoting the endogenous
      production of degraded hyaluronic acid in osteoarthritis. The use of these
      compounds requires the adherence to a set of specific techniques, designed for
      the correct intra-articular infiltration of the viscosupplement without the need
      to inflict an additional traumatic load on the patient; these techniques with
      special reference to the patient affected by knee osteoarthritis (gonarthritis)
      are described in this article, which also highlights the criteria for choosing
      the ideal viscosupplement, the one most similar to hyaluronic acid native in
      healthy young people, and one whose therapeutic use reports greater clinical
      benefits in the short and long term.

PMID- 29641862
TI  - [The Working Efficiency and Health Conditions of Workers].
AB  - The article presents the results of expert evaluation of impact of workers'
      health on labor efficiency. The key problems related to health support at
      industrial enterprises are considered too. The pilot study covered 20 experts
      (administrators, deputy directors of HR departments and departments of
      occupational care and industrial safety of large industrial enterprises). The
      study was carried out with participation of specialists of the Russian public
      opinion research center (VCIOM). The study results demonstrate a high actuality
      of issues related to health of workers support for employers. The low labor
      efficiency is one of leading motivations of implementing the systems of health
      care management.

PMID- 29641863
TI  - [The Scientific Analysis of Factors of Physical Accessibility of Medications as
      Exemplified by the Sakhalin Oblast. Part II].
AB  - The Sakhalin oblast is considered as a detailed example of physical accessibility
      of pharmaceuticals with regards to time-space factors and assortment
      accessibility. The conclusions are made concerning universality of factors of
      accessibility and availability of characteristics to be taken into account in
      every subject. The analysis of factors of accessibility in the subject permits to
      establish risk zones preventing accessibility of pharmaceuticals to population.

PMID- 29641865
TI  - [The Impact of Medical and Non-Medical Factors on Population Mortality: the
      Social Factors].
AB  - The study was carried out to analyze national and international publications
      evaluating impact of social factors on population mortality. The analysis was
      made on the basis of publications accessible in prints and electronic format
      (MEDLINE, EMBASE, ISI Web of Science) in Russian and English from 1990 to 2015.
      The results of generalized studies testify a valuable impact on standardized
      mortality coefficients of such factors as social support and social integration,
      higher level of education, higher social position, global peacefulness index,
      developed infrastructure. The negative impact is made by social stress, lower
      level of education, higher level of unemployment, social deprivation. It is
      established that social factors are ones the main factors effecting population
      mortality level. The effect of social factors is ambivalent and heterogeneous in
      time and by population groups. he quantitative evaluation of effect of every one
      of social factors is difficult.

PMID- 29641864
TI  - [The Evaluation of Medical Demographic and Economic Losses of the Region
      Conditioned by Mortality of Lung Cancer].
AB  - The article presents evaluation of medical demographic and economic losses of
      population of the Krasnoyarskii kraii conditioned by mortality of lung cancer in
      2010-2014 using DALY technology. In the Krasnoyarskii kraii, during 2010-2014
      64,712 individuals died because of lung cancer. The mortality of male population
      surpasses corresponding indices of mortality of females up to 3.9 times. In the
      region, the standardized indicator mortality of lung cancer among males annually
      surpasses the same indicator among females at maximum up to 8.1 times. The DALY
      maximal absolute losses of among males were registered in 2010 and 2013 and fell
      on age group of 55-59 years and among females on the age group of 60-64 years in
      2014. The maximal (up to 5.2 times) difference in values of DALY indicator was
      established in 2010 between male and female population. the maximal gap in in
      DALY indices between male and female population was established in the age of 55
      59 years. Almost half of DALY losses among males was established in 2013 and
      among females in 2014. The total losses of gross regional product in the region
      because of mortality conditioned by lung cancer made up to 29.8 billions of
      rubles in 2010-2014.

PMID- 29641866
TI  - [The Results of Self-Assessment by Medical Organizations Their Correspondence to
      Proposals (Practical Recommendations) of the Roszdravnadzor Concerning
      Organization of Internal Control of Quality and Safety of Medical Activity].
AB  - The article presents the analysis of the results of internal audits (self-rating)
      in medical organizations implemented on the basis of Proposals (practical
      guidelines) of the Roszdravnadzor concerning organization of inner control of
      quality and safety of medical activities in medical organization (hospital). The
      self-rating was implemented by the medical organizations themselves according the
      common criteria of the Proposals as provided the following plan: planning of self
      rating, collection and processing of data, application of self-rating, analysis
      of obtained results, preparation of report. The article uses the results of self
      rating of medical organizations corresponding to following criteria: profile of
      activity-multi-field hospital-number of beds more than 350-state property. The
      self-rating was implemented according to 11 basic parts of the Proposals. The
      criteria were developed for every part. The evaluation lists developed on the
      basis of the given Proposals permitted to medical organizations to independently
      establish problems in their activities. Within the framework of implemented self
      rating medical organizations mentioned the directions of activity related to
      personnel management, identification of personality of patient, support of
      epidemiological and surgical safety as having significant discrepancies with the
      Proposals and requiring implementation of improvement measures.

PMID- 29641867
TI  - [The Impact of Labor Conditions on Health Conditions of Traumatologists of
      Emergency Service].
AB  - The organization of emergency medical care varies from one country to another.
      However, the basic requirements applied to specialists in case of emergency
      curative diagnostic measures are common: fast feedback, professionalism,
      emotional stability. Therefore, the key characteristic of emergency medicine is
      to instantly react twenty-four hours per day. The medical workers of considered
      category are in condition of increased physical and mental loading. According the
      WHO concept, a negative impact of working environment is a key factor of
      development of professional burn-out syndrome. Despite that in publications there
      are enough data concerning prevalence of this syndrome among physicians, there is
      no common approach to establishment of causes of its development. The
      sociological survey was carried out using the technique of the Maslach's Burnout
      Inventory questionnaire concerning traumatologists of emergency medical care in
      profile departments of metropolitan medical organizations. It is established that
      emergency as a special operating mode is a key factor in development of
      professional burn-out syndrome. Its development results in both deterioration of
      mental and physical health of medical workers of the given category and negative
      impact on efficiency of their work.

PMID- 29641868
TI  - [The Indices of Common and Early Detection of Urological Pathology as Criteria of
      Efficiency of Urological Care Rendering].
AB  - The comparative statistical and logical analysis of curves of dynamics of common
      and early detection of urological pathology was implemented with purpose of
      evaluating efficiency of functioning of regional urological service in the format
      of developed three-level system of medical care as exemplified by the Voronezh
      oblast. The obtained statistical data testify a significant increasing of common
      detection and detection at early stages of urolithiasis, benign hyperplasia and
      prostate cancer. This outcome is an evidence of partial or complete realization
      of transition from model of medical care by appealability to model by detection
      at the expense of implementation of developed three-level system of medical care
      of population in the region.

PMID- 29641869
TI  - [The Medical Social Efficiency of Rehabilitation of Patients Having Cerebral
      Stroke in Ambulatory Conditions].
AB  - The article substantiates efficiency of medical social rehabilitation activities
      in out-patient conditions on the basis of study of health conditions, life-style
      and medical care organization of patients with ischemic stroke. The obtained data
      demonstrated a higher efficiency of complex rehabilitation therapy. The efficient
      application of possibilities of out-patient polyclinic institution increases the
      level of physiological, psychological and social adaptation of patients.

PMID- 29641870
TI  - [The Evaluation of Necessity of Individuals Older Aged 50 Years and Older in
      Outpatient Polyclinic Services].
AB  - The department of X-ray diagnostics of the out-patient center was used to carry
      out a sociological survey with the purpose of studying such social demographic
      characteristics of patients as level of education, material condition, benefits
      availability, degree of employment. The patients of advanced age visit the out
      patient center most often for X-ray examinations because of diseases of nervous
      system, neoplasms and diseases of musculoskeletal system. In average, the
      patients wait their line for examination during up to three days. In both cases
      of implementing examination by appointment of hospital physician or by initiative
      of patient oneself (for fee) waiting time decreases. The main causes of using of
      paid medical care is the queue for free-of-charge examination and lacking of
      needed physician in polyclinic. The most of patients characterize scope of
      services provided in out-patient center as inadequate. At that, less than a half
      of respondents are agreed for broadening of paid diagnostic services. The
      readiness of patients for broadening of scope of paid services at the pre
      hospital stage of treatment depend on their economic condition and employment
      status. The maximal readiness is expressed by working people with good economic
      condition. The application of obtained data provides an opportunity of optimizing
      of diagnostic care optimization.

PMID- 29641871
TI  - [The Principles of Project Management Training of Administrators and Workers of
      Medical Organizations].
AB  - The article substantiates actuality of development of managerial and
      communicative competences in administrators and employees of medical
      organizations. the model of competences is presented, including training program
      for physician and medical nurse. also a model of competences and training program
      for administrators of medical organizations is presented. The expected results
      are formulated concerning training of medical personnel in the field of project
      management.

PMID- 29641872
TI  - [The Personnel Problem in Specialized Opthalmologic Care].
AB  - The article presents results of analysis of staffing with ophthalmologists in
      ambulatory polyclinic section in the Russian Federation and the federal okrugs in
      2007-2012. The significant variations in analyzed indices are established and
      also increasing of moonlighting among specialists against the background of
      increasing of morbidity of diseases of eye and its adnexa and aging of
      population. The most unfavorable situation emerged in the south Federal okrug
      where deficiency of ophthalmologists made up to 11.7%. Alongside with that,
      staffing with specialists of this profile drastically decreased up to 6.7% in the
      Dalnevostochnii Federal okrug.

PMID- 29641873
TI  - [On Choice of Profession of Pharmacist by Students of Moscow Universities].
AB  - The development of personality strongly depends on correspondence of chosen
      profession to capacities and interests of specialist, labor market demand and
      possibility of career making. The particular dynamics is observed in alteration
      of conception of professions and professional activities because information
      revolution resulted in shifting from mono-professionalism to mastering of several
      professions at once. The profession of pharmacist also passed through several
      alterations following development of pharmaceutical industry. The results of
      survey of opinions of students of pharmaceutical faculties concerning choice of
      profession of pharmacist demonstrate an actual situation at industry market and
      give an opportunity of forecasting its development in Moscow for nearest years.

PMID- 29641874
TI  - [The Institutionalization of Traumatology and Orthopedics in Russia].
AB  - The article considers process of institutionalization of Russian traumatology and
      orthopedics. It is demonstrated that process of institutionalization goes on in
      undulating manner takes in average about 50 years, from the moment of statement
      of a question to ultimate assignment of specialty of traumatology and
      orthopedics, organization of institutes and chairs of traumotology and
      orthopedics with alternation of dominance of ducens- and mandate model. On the
      basis of developed criteria chronological clusters and periods. The selection of
      traumatology and orthopedics into independent field was related not to a
      transition to a new stage of development of science but to general process of
      increasing of differentiation and specialization in medicine.

PMID- 29641875
TI  - [The Problem of Training of Professors of Medicine in Russia of the Beginning of
      XIX Century].
AB  - The article considers an unknown aspect in history of medical education - the
      project of training of professors of medicine of "natural Russians". The author
      of the project was Ya.V. Wylie, the physician-in-ordinary of the Emperor, the
      chief medical inspector of army and the president of the Medical surgical
      academy. His intention was implemented in 1817-1818 and resulted in cessation of
      international employments of professors of medicine for Russian universities and
      medical surgical academies and organization of the system of specialized training
      of graduates of Russian medical schools to title of professor as well. The given
      subject permits to clarify why foreign physician at Russian service was against
      international employments and stood up for "national" interests of the Russian
      Empire. The archive evidences permit to establish conditions of birth of such an
      initiative. The biographies of participants of the project give rise to trace
      long-term aftermaths of its implementation for history of medical profession in
      the Russian Empire.

PMID- 29641876
TI  - [V.I. Smidovich: a Whole Life to Local Community Good].
AB  - The article considers public and medical activities of Vikentii Ignatievich
      Smidovich, one of the most prominent physicians of Tula of the end of XIX
      century. His role in the organization and activities of the Tula society of
      physicians is analyzed. The particular attention is paid to activities of V.I.
      Smidovich related to amelioration of sanitary conditions of Tula, amelioration of
      conditions and increasing of longevity of life of residents, support of
      population with free medical care. The attempt is made to trace the role of a
      single personality in the process of historical, cultural, social development of
      a particular region. The article presents a short description of industrial Tula
      at the end of XIX century as a prerequisite to socially directed activity of
      educated sections of population, including physicians-humanists. The personal
      characteristics of V.I. Smidovich are emphasized that permitted him to gain a
      higher authority among patients and colleagues and to achieve established tasks.
      The article deals with the theme of life and death as an ethical argument,
      "natural heroism" of medical profession. The fragment of case history composed by
      V.I. Smidovich himself is presented. The emphasis is also made on the role of
      Smidovich-father in the formation of creed and creative direction of V.V.
      Veresaiev, his son.

PMID- 29641877
TI  - [N.M. Serkov - the First Head of the Baikal Oblast Department of Health Care of
      the Far-East Republic].
AB  - The article presents supplemented biography of physician Nikolaii Mikhaylovich
      Serkov. His enormous input into becoming and development of state health care
      system on the territory of ethnic Buryatia during all period of existence of the
      Far-Eastern Republic.

PMID- 29641878
TI  - SURVEILLANCE OF HIV-1 DRUG-RESISTANCE MUTATIONS IN THAILAND FROM 1999 TO 2014.
AB  - Antiretroviral resistance has long been a serious problem in Thailand. Inorder to
      monitor developmental rate of mutations and its impact of the nationalpolicy,
      frequency of drug-resistance mutations in HIV-1 reverse transcriptase (RT)and
      protease (PR) were analyzed from 24,279 blood plasma samples collected from1999
      to 2014. HIV-1 drug resistance mutations were influenced by drugs that havebeen
      used widely as first-line regimens. M184I/V was the most common (53.1%prevalence)
      RT inhibitor (NRTI) mutation. Other NRTI-associated mutations
      increaseddramatically after the Universal Coverage Scheme was launched in
      2007,but declined on the whole after introduction of the Thai National Guidelines
      in2010. However, non-NRTI-associated mutations increased between 1999 and
      2007,but have remained constant since, with Y181I/C the most (31.4%) prevalent.
      PRdrug-associated mutations (M36I/L/V, H69K/R and L89I/M/V) previously
      consideredas CRF01_AE polymorphisms constituted > 90% prevalence in all
      samples.The launch of antiretroviral treatment influenced the pattern of
      mutations and theUniversal Coverage Scheme also impacted the rate of development
      of resistancemutations on a national scale. Drug resistance trends in Thailand
      could be ascribedto drug regimens that have been used for over a decade. Results
      from thisstudy can be used as indicators of the success of the Universal Coverage
      Scheme.Knowledge of the trend of HIV drug-resistance mutations, past and present,
      isessential in formulating an effective antiretroviral treatment strategy.

PMID- 29641879
TI  - EFFORTS TO INCREASE THE USE OF HIV TESTING SERVICES : WHAT INTERVENTIONS HAVE
      WORKED IN THAILAND?
AB  - We reviewed and analyzed published research concerning efforts to increaseregular
      use of HIV testing services in Thailand. Separate studies suggestedthat the
      creation of participatory and creative online spaces for information sharingand
      promoting community-based testing positively influence levels of HIVtesting,
      including repeat-testing in some cases. Population targeted approaches,using same
      day rapid tests, and using diverse locations for testing (medical andnon-medical)
      may improve rates of testing. Thailand shows an example of successfulHIV
      management and reduction. The challenge is to continue towardszero new infections
      and end an epidemic that is increasingly associated amongpeople with specific
      risk behaviors. These characteristics make Thailand a casestudy for consideration
      by other national HIV programs.

PMID- 29641880
TI  - DENGUE PREVENTION: CONFIRMATORY FACTOR ANALYSIS OF RELATIONSHIPS BETWEEN ECONOMIC
      STATUS, KNOWLEDGE, ATTITUDES AND PRACTICE, VACCINE ACCEPTANCE AND WILLINGNESS TO
      PARTICIPATE IN A STUDY.
AB  - The aim of this study was to study the relationships between economicstatus,
      knowledge, attitude and practice regarding dengue fever (DF), attitudetowards
      vaccination against dengue virus infection, willingness to participate ina study
      on dengue, and acceptance of a dengue vaccine. Information on variablesof
      interest was collected in questionnaire-assisted interviews during a
      communitybasedcross-sectional survey conducted in Aceh, Indonesia. A proposed
      relationshipmodel was tested using Confirmatory Factor Analysis (CFA), and an
      ExploratoryFactor Analysis (EFA) was used to reconstruct an alternative
      relationshipmodel among variables. Our proposed relationship model differed from
      the resultof the EFA. The CFA indicated that knowledge and attitudes towards DF
      had thestrongest relationship. We also found several direct relationships between
      sets ofvariables: a) economic status and knowledge on DF, b) economic status and
      practicesregarding DF, c) knowledge and practices regarding DF, d) attitudes
      towardsDF and dengue vaccine acceptance, as well as e) attitudes towards
      vaccination anddengue vaccine acceptance. There was no relationship between
      economic statusand dengue vaccine acceptance. In conclusion, our model suggested
      that the mostsuitable factor to be targeted for improving dengue prevention was
      knowledgeabout DF. In addition, improving attitudes towards vaccination seemed to
      be themost appropriate effort to increase public acceptance of a dengue vaccine.

PMID- 29641881
TI  - LONG-TERM PROTECTIVE RABIES ANTIBODIES IN THAI CHILDREN AFTER PRE-EXPOSURE RABIES
      VACCINATION.
AB  - Rabies is a viral zoonosis affecting around 16,000-39,000 people annually.Pre
      exposure vaccination should be offered to individuals at high risk ofrabies
      exposure and is suggested for children living in rabies endemic
      areas.Theincidence rate of dog bite in the test group was 14.1/1,000 person
      years. Intradermal(ID) route of administration is considered an alternative to
      the standardintramuscular (IM) administration, and reduces vaccination cost. A 3
      year clinicalstudy of a rabies vaccine administered IM or ID to 12-18-month-old
      Thai children,simultaneously with a Japanese encephalitis (JE) vaccine (M49P2
      study),revealed that all regimens used elicited an adequate immune response. In
      orderto determine the long-term (4-8 years) rabies neutralizing antibody titers
      inducedby the pre-exposure regimens, blood was collected annually from 68 from
      theM49P2 study and analyzed using a rapid fluorescence focus inhibition test.
      Full-IM(three doses of 1 ml/dose), half-IM(three doses of 0.5 ml/dose), and 3
      ID(threedoses of 0.1 ml/dose) regimens induced antibody titers above the
      seroprotectivelevel throughout the study period. However, the 2-ID(two doses of
      0.1 ml/dose)group had sub-seroprotective titer of 6.7%, 13.4%, 25.0%, and 36.4%
      in year 5, 6, 7,and 8, respectively. A secondary immune response was induced by
      rabies boostervaccination. This study demonstrates a reduced-dose rabies regimen
      may lowerthe cost of long-term protection against rabies for vulnerable
      populations, thusimproving the cost-effectiveness of pre-exposure rabies
      vaccination in children.

PMID- 29641882
TI  - COMPARISON OF GeneXpert MTB/RIF ASSAY WITH CONVENTIONAL AFB SMEAR FOR DIAGNOSIS
      OF PULMONARY TUBERCULOSIS IN NORTHEASTERN THAILAND.
AB  - Among infectious agents, Mycobacterium tuberculosis remains one ofthe most
      significant causes of death worldwide. Rapid and accurate diagnosisof pulmonary
      tuberculosis (TB) remains a great challenge. GeneXpert MTB/RIFassay is a novel
      integrated diagnostic system for rapid diagnosis of TB and particularlyof
      rifampicin-resistant strains. A study was conducted between January2010 and
      December 2014 to compare the performance of the sputum GeneXpertMTB/RIF assay
      with the conventional sputum AFB smear for diagnosis of activepulmonary TB in
      Thailand, a country with a high burden of this disease. Of the125 patients who
      had cough and/or prolonged fever together with abnormal chestradiograph, 63 were
      diagnosed as having pulmonary TB by mycobacterium cultureassay, while the
      remaining subjects were considered of having TB-like conditions,viz non
      tuberculous mycobacterium infection (NTM), bacterial pneumonia orbronchogenic
      carcinoma. Two-thirds of the patients had underlying diseases, eg,diabetes
      mellitus (19 patients), autoimmune diseases (14), and HIV (6). Amongpatients with
      positive diagnosis of M. tuberculosis infection, 30 were AFB smearpositive and 53
      by sputum GeneXpert MTB/RIF method; among patients negativefor M. tuberculosis
      infection, 4 were AFB smear positive and 5 by GeneXpert MTB/RIF assay.
      Sensitivity and specificity of the sputum AFB smear and GeneXpertMTB/RIF assay
      test were 48% (95% CI: 35-61) and 84% (95% CI: 73-92), and 94% (95%CI: 84-98) and
      92% (95% CI: 82-97), respectively. Diagnostic performance of theGeneXpert MTB/RIF
      assay among AFB smear positive patients was higher thanamong AFB smear negative
      patients (adjusted OR 6.7; 95% CI: 2.3-19.9). Earlierdiagnosis of pulmonary TB
      using GeneXpert MTB/RIF assay will lead to earlierappropriate treatment and
      provide opportunities to interrupt TB transmission.

PMID- 29641883
TI  - DRUG RESISTANCE PATTERN AND MOLECULAR CHARACTERIZATION OF MYCOBACTERIUM
      TUBERCULOSIS STRAINS IN PUNJAB, PAKISTAN.
AB  - Tuberculosis (TB) is a cause of death from a single infectious agent
      Mycobacteriumtuberculosis (MTB), leading to approximately 2.5 million deaths
      annuallyworldwide. Information regarding prevalence and pattern of drug
      resistanceamong TB patients in Pakistan remains inadequate due to the country's
      limitedresources. This study compared conventional diagnostic techniques with a
      PCRbasedassay targeting IS6110 sequence. In addition, MTB drug resistant
      profilesagainst four first-line drugs (ethambutol, isoniazid, rifampin, and
      streptomycin)from new and retreatment cases of TB. From 101 sputum samples
      microscopicexamination of Ziehl-Neelsen-stained smears and culturing on
      Lowenstein Jensenmedium resulted in 96% and 100% positives, compared to 98% by
      PCR. Prevalenceof MDR-MTB was 41.5% and 58.5% among new (n = 51) and
      retreatment(n = 50) cases, but 10% of the former group were sensitive to all four
      first-lineanti-TB drugs. Thus, MDR-MTB is highly prevalent among TB patients in
      PunjabProvince, Pakistan (where the study was conducted) and, although PCR
      amplificationof MTB-specific IS6110 sequence was rapid, it lacked the sensitivity
      ofthe culture assay.

PMID- 29641884
TI  - HAEMOPHILUS INFLUENZAE FROM PATIENTS AT THE LARGEST UNIVERSITY TERTIARY CARE
      CENTER, THAILAND 2012 - 2015.
AB  - Haemophilus influenzae was isolated from 556 different patients, mostly10 years
      or under, at a tertiary referral hospital in Bangkok, Thailand during 2012- 2015.
      Peak period of detection was from January to March. Thirty-nine percent ofthe
      isolates were beta-lactamase positive. beta-Lactamase-negative ampicillin
      resistantH. influenzae (BLNAR) constituted 2% of beta-lactamase-negative cases.
      H. influenzaewas susceptible to ampicillin (58%), amoxicillin/clavulanate (99%),
      cefotaxime(100%), ceftriaxone (100%), cefuroxime (99%), ciprofloxacin (99%),
      chloramphenicol(86%), tetracycline (75%), and trimethoprim-sulphamethoxazole
      (52%).beta-Lactamase-producing isolates (72%) showed high minimal inhibitory
      concentration(MIC) to ampicillin (128-516 MUg/ml) and all BLNAR isolates low
      ampicillinMIC (2-16 MUg/ml). These findings indicate that the level of ampicillin
      resistancein H. influenzae depended on differences in resistance mechanism.

PMID- 29641885
TI  - Hierarchical Emergence and Dynamic Control of Chirality in a Photoresponsive
      Dinuclear Complex.
AB  - Chiroptical photoswitches are of interest from a viewpoint of applications in
      advanced information technologies. We report dynamic on-off photoswitching of
      circularly polarized luminescence (CPL) in a binuclear europium complex system.
      Two coordination units are arranged closely in a chiral fashion by a
      photoresponsive ligand with a one-handed helical structure. The chirality in the
      helical scaffold is hierarchically transferred to the chirality in nine
      coordinate complex sites. The chiral close arrangement of complex units induces
      the enrichment of a specific chiral coordination structure in the nine-coordinate
      europium sites. The chiral arrangement of complex units is switched in
      conjunction with the photoinduced helix-nonhelix structural change in the
      photoresponsive framework, demonstrating on-off switching of CPL with high
      contrast.

PMID- 29641886
TI  - Photoresponsive Aqueous Dissolution of Poly( N-Isopropylacrylamide)
      Functionalized with o-Nitrobenzaldehyde through Phase Transition.
AB  - We report a sharp photoinduced aqueous dissolution of the copolymer through phase
      transition based on the photochemical reaction of o-nitrobenzaldehyde (NBA) and
      the principle of polymer effect. We synthesized the copolymers having poly( N
      isopropylacrylamide) main chain and NBA side chain at 4, 7, and 10 mol %
      functionalizations and analyzed their photoresponsive characteristics. Light with
      365 nm wavelength converted NBA groups at copolymer side chains to carboxylic
      acid efficiently at the rate of 7.3 cm2/J, and in the case of 10 mol %
      functionalization, the irradiation dosage no more than 56 mJ/cm2 induced sharp
      aqueous dissolution of the copolymer thin layer in pH 7.4 at 25  degrees C. As
      example applications, we demonstrated on-demand release of polyethylene beads and
      fluorescent-labeled albumins, which had been immobilized on a substrate surface
      via the copolymers, by the precisely controlled light irradiation using a
      microprojection system. Also, we examined application of the copolymers to the
      selective recovery of living cells from culture substrate under microscopic
      observation. As a result, mild light irradiation at room temperature triggered
      immediate detachment of the cultured adherent cells only in the irradiated areas
      without critical influence on their viability.

PMID- 29641887
TI  - N-H...S Interaction Continues To Be an Enigma: Experimental and Computational
      Investigations of Hydrogen-Bonded Complexes of Benzimidazole with Thioethers.
AB  - The N-H...S hydrogen bond, even though classified as an unconventional hydrogen
      bond, is found to bear important structural implications on protein structure and
      folding. In this article, we report a gas-phase study of the N-H...S hydrogen
      bond between the model compounds of histidine (benzimidazole, denoted BIM) and
      methionine (dimethyl sulfide, diethyl sulfide, and tetrahydrothiophene, denoted
      Me2S, Et2S, and THT, respectively). A combination of laser spectroscopic methods
      such as laser-induced fluorescence (LIF), two-color resonant two-photon
      ionization (2cR2PI), and fluorescence depletion by infrared spectroscopy (FDIR)
      is used in conjunction with DFT and ab initio calculations to characterize the
      nature of this prevalent H-bonding interaction in simple bimolecular complexes. A
      single conformer was found to exist for the BIM-Me2S complex, whereas the BIM
      Et2S and BIM-THT complexes showed the presence of three and two conformers,
      respectively. These conformers were characterized on the basis of IR
      spectroscopic results and electronic structure calculations. Quantum theory of
      atoms in molecules (QTAIM), natural bond orbital (NBO), and energy decomposition
      (NEDA) analyses were performed to investigate the nature of the N-H...S H-bond.
      Comparison of the results with the N-H...O type of interactions in BIM and indole
      revealed that the strength of the N-H...S H-bond is similar to N-H...O in these
      binary gas-phase complexes.

PMID- 29641888
TI  - Light Driven Electron Transfer in Methylbipyridine/Phenol Complexes Is Not Proton
      Coupled.
AB  - The pursuit of systems that undergo optical electron proton transfer (photo-EPT)
      is very attractive, due to the wealth of information contained in the absorption
      spectra of such complexes. However, separating photo-EPT transitions from
      conventional charge transfer states remains a major challenge. In this study, we
      show that optical charge transfer in a complex between 4-methoxyphenol and N
      methyl-4,4'-bipyridyl, previously assigned to occur through photo-EPT involving a
      hydrogen bond between the reactants ( Gagliardi , C. J. ; ; Wang , L. ; ; Dongare
      , P. ; ; Brennaman , M. K. ; ; Papanikolas , J. M. ; ; Meyer , T. J. ; ; Thompson
      , D. W. Proc. Natl. Acad. Sci. U.S.A. 2016 , 113 , 11106 - 11109 ), does not lead
      to protonation of the acceptor molecule. Additionally, we propose that
      association of the complex is likely due to donor-acceptor interactions rather
      than hydrogen bonding.

PMID- 29641890
TI  - Efficient Targeting Drug Delivery System for Lewis Lung Carcinoma, Leading to
      Histomorphological Abnormalities Restoration, Physiological and Psychological
      Statuses Improvement, and Metastasis Inhibition.
AB  - Lung cancer is a kind of malignant tumor with high morbidity and metastasis
      tendency. Gambogic acid (GA) has demonstrated significant antitumor activity in
      vitro, but its poor water-solubility and adverse effects restrict its application
      in vivo and in clinic. In this study, a passive-targeting GA delivery system was
      prepared for orthotopic Lewis lung carcinoma model mice. Besides the ~7 MUm size
      distribution, slow and steady in vitro drug release in a week, high targeting
      effect to lung, effective restoration of histomorphological abnormalities in
      lung, maintaining on bodyweight, and prolongation on survival time, excellent
      improvements of the GA-loaded particles on physiological and psychological
      statuses and obvious inhibition on tumor metastasis to liver have also been
      observed, through the measurements of Porsolt forced swim, hypoxic tolerance
      time, ultrastructure of pulmonary capillary, pulmonary vascular permeability, and
      hepatic histological change. These results suggest that this GA-loaded particle
      may be an ideal approach to achieve satisfactory therapeutic function on lung
      cancer.

PMID- 29641889
TI  - Three-Dimensional Silicon Electronic Systems Fabricated by Compressive Buckling
      Process.
AB  - Recently developed approaches in deterministic assembly allow for controlled,
      geometric transformation of two-dimensional structures into complex, engineered
      three-dimensional layouts. Attractive features include applicability to wide
      ranging layout designs and dimensions along with the capacity to integrate planar
      thin film materials and device layouts. The work reported here establishes
      further capabilities for directly embedding high-performance electronic devices
      into the resultant 3D constructs based on silicon nanomembranes (Si NMs) as the
      active materials in custom devices or microscale components released from
      commercial wafer sources. Systematic experimental studies and theoretical
      analysis illustrate the key ideas through varied 3D architectures, from
      interconnected bridges and coils to extended chiral structures, each of which
      embed n-channel Si NM MOSFETs (nMOS), Si NM diodes, and p-channel silicon MOSFETs
      (pMOS). Examples in stretchable/deformable systems highlight additional features
      of these platforms. These strategies are immediately applicable to other wide
      ranging classes of materials and device technologies that can be rendered in two
      dimensional layouts, from systems for energy storage, to photovoltaics,
      optoelectronics, and others.

PMID- 29641891
TI  - Enantioselective Toxicity in Adult Zebrafish ( Danio rerio) Induced by Chiral
      PCB91 through Multiple Pathways.
AB  - This study aimed to further investigate the toxic mechanism of chiral
      polychlorinated biphenyl (PCB) 91 in adult zebrafish ( Danio rerio) exposed to
      racemic (rac-), (+)-, or (-)-PCB91 for 63 days. The enantioselective mortalities
      of adult zebrafish exposed to rac-/(+)-/(-)-PCB91 were 95.86, 50.08, and 81.50%,
      respectively. Tubular necrosis and cellular hypertrophy occurred in the kidneys
      of (-)-PCB91-treated groups, whereas demyelination and immune cell infiltration
      occurred in brains of the rac-, (+)-, and (-)-PCB91-treated groups. Additionally,
      exposure to chiral PCB91 enantioselectively induced neurotoxicity, apoptosis, and
      inflammation in brain tissues owing to perturbations of gene expression, protein
      content and sphingolipid levels. The high mortality after rac-/(+)-PCB91 exposure
      might be due to toxic effects on brain tissue, while the high mortality after (-)
      PCB91 exposure might be due to toxic effects on kidney as well as brain tissues.
      Thus, our findings offer an important reference for elucidating the
      enantioselective toxicological mechanism of chiral PCBs in aquatic organisms.

PMID- 29641892
TI  - Acid-Resistant Mesoporous Metal-Organic Framework toward Oral Insulin Delivery:
      Protein Encapsulation, Protection, and Release.
AB  - Diabetes affects millions of people worldwide and the number of diagnoses
      continues to climb annually. Though several effective medications and therapeutic
      methods have been developed to treat type 1 (T1DM) and type 2 (T2DM) diabetes
      mellitus, direct insulin injection remains the only effective treatment for
      insulin resistant (IR) diabetes patients. Here, we immobilize insulin in a
      crystalline mesoporous metal-organic framework (MOF), NU-1000, and obtain a high
      loading of ~40 wt % in only 30 min. The acid-stable MOF capsules are found to
      effectively prevent insulin from degrading in the presence of stomach acid and
      the digestive enzyme, pepsin. Furthermore, the encapsulated insulin can be
      released from NU-1000 under simulated physiological conditions.

PMID- 29641893
TI  - Exploration of Nanoparticle-Mediated Photothermal Effect of TMB-H2O2 Colorimetric
      System and Its Application in a Visual Quantitative Photothermal Immunoassay.
AB  - The exploration of new physical and chemical properties of materials and their
      innovative application in different fields are of great importance to advance
      analytical chemistry, material science, and other important fields. Herein, we,
      for the first time, discovered the photothermal effect of an iron oxide
      nanoparticles (NPs)-mediated TMB (3,3',5,5'-tetramethylbenzidine)-H2O2
      colorimetric system, and applied it toward the development of a new NP-mediated
      photothermal immunoassay platform for visual quantitative biomolecule detection
      using a thermometer as the signal reader. Using a sandwich-type proof-of-concept
      immunoassay, we found that the charge transfer complex of the iron oxide NPs
      mediated one-electron oxidation product of TMB (oxidized TMB) exhibited not only
      color changes, but also a strong near-infrared (NIR) laser-driven photothermal
      effect. Hence, oxidized TMB was explored as a new sensitive photothermal probe to
      convert the immunoassay signal into heat through the near-infrared laser-driven
      photothermal effect, enabling simple photothermal immunoassay using a
      thermometer. Based on the new iron oxide NPs-mediated TMB-H2O2 photothermal
      immunoassay platform, prostate-specific antigen (PSA) as a model biomarker can be
      detected at a concentration as low as 1.0 ng.mL-1 in normal human serum. The
      discovered photothermal effect of the colorimetric system and the developed new
      photothermal immunoassay platform open up a new horizon for affordable detection
      of disease biomarkers and have great potential for other important material and
      biomedical applications of interest.

PMID- 29641894
TI  - Resolving the Controversial Existence of Silicene and Germanene Nanosheets Grown
      on Graphite.
AB  - The highly oriented pyrolytic graphite (HOPG) surface, consisting of a dangling
      bond-free lattice, is regarded as a potential substrate for van der Waals
      heteroepitaxy of two-dimensional layered materials. In this work, the growth of
      silicon and germanium on HOPG is investigated with scanning tunneling microscopy
      by using typical synthesis conditions for silicene and germanene on metal
      surfaces. At low coverages, the deposition of Si and Ge gives rise to tiny and
      sparse clusters that are surrounded by a honeycomb superstructure. From the
      detailed analysis of the superstructure, its comparison with the one encountered
      on the bare and clean HOPG surface, and simulations of the electron density, we
      conclude that the superstructure is caused by charge density modulations in the
      HOPG surface. At high coverages, we find the formation of clusters, assembled in
      filamentary patterns, which indicates a Volmer-Weber growth mode instead of a
      layer-by-layer growth mode. This coverage-dependent study sets the stage for
      revisiting recent results alleging the synthesis of silicene and germanene on the
      HOPG surface.

PMID- 29641895
TI  - Fine Tuning of Core-Shell Structure of Hyaluronic Acid/Cell-Penetrating
      Peptides/siRNA Nanoparticles for Enhanced Gene Delivery to Macrophages in
      Antiatherosclerotic Therapy.
AB  - Hyaluronic-acid (HA)-coated LOX-1-specific siRNA-condensed cell-penetrating
      peptide (CPP) nanocomplexes (NCs) were developed for targeted gene delivery to
      macrophages and suppression of lipid accumulation. The HA coating facilitated the
      accumulation of nanoparticles at leaky endothelium overexpressing CD44 receptors
      and was further degraded by hyaluronidase (HAase) intraplaques for exposing the
      naked CPP NCs and achieving the ultimate location into macrophages. The surface
      coating of HA was verified by the increased particle size, inverted zeta
      potential, and TEM images. The targeting mechanism was studied on the established
      injured endothelium-macrophage coculture system, which revealed that modification
      of higher molecular weight HA and higher HA coating density on NCs, termed as NPs
      3, improved the intracellular uptake of nanoparticles by macrophages. Macrophages
      internalized NCs via caveolae-mediated endocytosis pathway. Moreover, NPs-3
      exhibited better cellular drug efficacy in preventing macrophage-derived foam
      cell formation than other preparations. Compared with NCs, HA decoration showed
      enhanced atherosclerotic-lesion-targeting efficiency, proven by results from ex
      vivo imaging. Furthermore, atheroprotective efficacy study in apoE-deficient mice
      showed that NPs-3 had the best potent efficacy, which was demonstrated by the
      fewest atherosclerotic lesions sizes and lipid accumulation, the lowest
      macrophage infiltration, and the lowest expression of monocyte chemoattractant
      protein-1 (MCP-1), respectively. Collectively, the HA-coated CPP NCs were
      promising nanocarriers for efficient macrophage-targeted gene delivery and
      antiatherogenic therapy.

PMID- 29641896
TI  - Nanoscale Electronic Conditioning for Improvement of Nanowire Light-Emitting
      Diode Efficiency.
AB  - Commercial III-Nitride LEDs and lasers spanning visible and ultraviolet
      wavelengths are based on epitaxial films. Alternatively, nanowire-based III
      Nitride optoelectronics offer the advantage of strain compliance and high
      crystalline quality growth on a variety of inexpensive substrates. However,
      nanowire LEDs exhibit an inherent property distribution, resulting in uneven
      current spreading through macroscopic devices that consist of millions of
      individual nanowire diodes connected in parallel. Despite being electrically
      connected, only a small fraction of nanowires, sometimes <1%, contribute to the
      electroluminescence (EL). Here, we show that a population of electrical shorts
      exists in the devices, consisting of a subset of low-resistance nanowires that
      pass a large portion of the total current in the ensemble devices. Burn-in
      electronic conditioning is performed by applying a short-term overload voltage;
      the nanoshorts experience very high current density, sufficient to render them
      open circuits, thereby forcing a new current path through more nanowire LEDs in
      an ensemble device. Current-voltage measurements of individual nanowires are
      acquired using conductive atomic force microscopy to observe the removal of
      nanoshorts using burn-in. In macroscopic devices, this results in a 33* increase
      in peak EL and reduced leakage current. Burn-in conditioning of nanowire
      ensembles therefore provides a straightforward method to mitigate nonuniformities
      inherent to nanowire devices.

PMID- 29641897
TI  - Design, Synthesis, and Enzymatic Evaluation of Novel ZnO Quantum Dot-Based Assay
      for Detection of Proteinase 3 Activity.
AB  - Herein, the synthesis and application of functionalized quantum dot-based
      protease probes is described. Such probes are composed of nontoxic ZnO
      nanocrystals decorated by amino groups followed by linker and labeled peptide
      attachment. Spherical NH2-terminated ZnO quantum dots (QDs) with the average size
      ranging from 4 to 8 nm and strong emission centered at 530 nm were prepared using
      the sol-gel method. The fluorescence of ZnO QDs was quenched by the BHQ1 moiety
      present on the N-terminal amino group of the peptide. The enzymatic cleavage of
      the peptide mediated by the proteinase 3 (PR3) bond resulted in an increase in
      the QD probe fluorescence. This observation was verified using both model and
      biological systems; and the picomolar detection limit was found to be more than
      30 times lower than that of the previously reported internally quenched peptide
      (a decrease in detection limit from 43 to 1.3 pmol was observed).

PMID- 29641899
TI  - Usefulness of a Dual Macro- and Micro-Energy-Dispersive X-Ray Fluorescence
      Spectrometer to Develop Quantitative Methodologies for Historic Mortar and
      Related Materials Characterization.
AB  - Wavelength dispersive X-ray fluorescence (WD-XRF) spectrometry has been widely
      used for elemental quantification of mortars and cements. In this kind of
      instrument, samples are usually prepared as pellets or fused beads and the whole
      volume of sample is measured at once. In this work, the usefulness of a dual
      energy dispersive X-ray fluorescence spectrometer (ED-XRF), working at two
      lateral resolutions (1 mm and 25 MUm) for macro and microanalysis respectively,
      to develop quantitative methods for the elemental characterization of mortars and
      concretes is demonstrated. A crucial step before developing any quantitative
      method with this kind of spectrometers is to verify the homogeneity of the
      standards at these two lateral resolutions. This new ED-XRF quantitative method
      also demonstrated the importance of matrix effects in the accuracy of the results
      being necessary to use Certified Reference Materials as standards. The results
      obtained with the ED-XRF quantitative method were compared with the ones obtained
      with two WD-XRF quantitative methods employing two different sample preparation
      strategies (pellets and fused beads). The selected ED-XRF and both WD-XRF
      quantitative methods were applied to the analysis of real mortars. The accuracy
      of the ED-XRF results turn out to be similar to the one achieved by WD-XRF,
      except for the lightest elements (Na and Mg). The results described in this work
      proved that MU-ED-XRF spectrometers can be used not only for acquiring high
      resolution elemental map distributions, but also to perform accurate quantitative
      studies avoiding the use of more sophisticated WD-XRF systems or the acid
      extraction/alkaline fusion required as destructive pretreatment in Inductively
      coupled plasma mass spectrometry based procedures.

PMID- 29641898
TI  - Qualitative and Quantitative Characterization of Composition Heterogeneity on the
      Surface of Spray Dried Amorphous Solid Dispersion Particles by an Advanced
      Surface Analysis Platform with High Surface Sensitivity and Superior Spatial
      Resolution.
AB  - Surface composition critically impacts stability (e.g., crystallization) and
      performance (e.g., dissolution) of spray dried amorphous solid dispersion (ASD)
      formulations; however, traditional characterization techniques such as Raman and
      infrared spectroscopies may not provide useful information on surface composition
      on the spray dried ASD particles due to low spatial resolution, high probing
      depth, and lack of quantitative information. This study presents an advanced
      surface characterization platform consisting of two complementary techniques: X
      ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass
      spectrometry (ToF-SIMS). Such a platform enables qualitative and quantitative
      measurements of surface composition for the fine spray dried ASD particles with
      ultrasurface-sensitivity (less than 10 nm from the surface) and superior spatial
      resolution (approximately 250 nm for ToF-SIMS). Both XPS and ToF-SIMS
      demonstrated that the polymer (PVPVA) was dominantly enriched on the surface of
      our spray dried naproxen-PVPVA ASD particles. Of a particular note was that XPS
      could differentiate two batches of spray dried ASD particles with a subtle
      difference in surface composition produced by varying feed solution solvents.
      This advanced surface characterization platform will provide essential surface
      information to understand the mechanisms underlying the impact of surface
      composition on stability (e.g., crystallization) and functionality (e.g.,
      dissolution) in future studies.

PMID- 29641900
TI  - Deciphering the Combined Effects of Environmental Stressors on Gene
      Transcription: A Conceptual Approach.
AB  - The use of classical mixture toxicity models to predict the combined effects of
      environmental stressors based on toxicogenomics (OMICS) data is still in its
      infancy. Although several studies have made attempts to implement mixture
      modeling in OMICS analysis to understand the low-dose interactions of stressors,
      it is not clear how interactions occur at the molecular level and how results
      generated from such approaches can be better used to inform future studies and
      cumulative hazard assessment of multiple stressors. The present work was
      therefore conducted to propose a conceptual approach for combined effect
      assessment using global gene expression data, as illustrated by a case study on
      assessment of combined effects of gamma radiation and depleted uranium (DU) on
      Atlantic salmon ( Salmo salar). Implementation of the independent action (IA)
      model in reanalysis of a previously published microarray gene expression dataset
      was performed to describe gene expression patterns of combined effects and
      identify key gene sets and pathways that were relevant for understanding the
      interactive effects of these stressors. By using this approach, 3120
      differentially expressed genes (DEGs) were found to display additive effects,
      whereas 279 (273 synergistic, 6 antagonistic) were found to deviate from
      additivity. Functional analysis further revealed that multiple toxicity pathways,
      such as oxidative stress responses, cell cycle regulation, lipid metabolism, and
      immune responses were enriched by DEGs showing synergistic gene expression. A key
      toxicity pathway of DNA damage leading to enhanced tumorigenesis signaling is
      highlighted and discussed in detail as an example of how to take advantage of the
      approach. Furthermore, a conceptual workflow describing the integration of
      combined effect modeling, OMICS analysis, and bioinformatics is proposed. The
      present study presents a conceptual framework for utilizing OMICS data in
      combined effect assessment and may provide novel strategies for dealing with data
      analysis and interpretation of molecular responses of multiple stressors.

PMID- 29641901
TI  - Theoretical Analysis of Optical Absorption and Emission in Mixed Noble Metal
      Nanoclusters.
AB  - In this work, we studied theoretically two hybrid gold-silver clusters, which
      were reported to have dual-band emission, using density functional theory (DFT)
      and linear and quadratic response time-dependent DFT (TDDFT). Hybrid functionals
      were found to successfully predict absorption and emission, although explanation
      of the NIR emission from the larger cluster (cluster 1) requires significant
      vibrational excitation in the final state. For the smaller cluster (cluster 2),
      the Delta H(0-0) value calculated for the T1 -> S0 transition, using the PBE0
      functional, is in good agreement with the measured NIR emission, and the
      calculated T2 -> S0 value is in fair agreement with the measured visible
      emission. The calculated T1 -> S0 phosphorescence Delta H(0-0) for cluster 1 is
      close to the measured visible emission energy. In order for the calculated
      phosphorescence for cluster 1 to agree with the intense NIR emission reported
      experimentally, the vibrational energy of the final state (S0) is required to be
      about 0.7 eV greater than the zero-point vibrational energy.

PMID- 29641902
TI  - Surface Plasmon-Mediated Nanoscale Localization of Laser-Driven sub-Terahertz
      Spin Dynamics in Magnetic Dielectrics.
AB  - We report spatial localization of the effective magnetic field generated via the
      inverse Faraday effect employing surface plasmon polaritons (SPPs) at Au/garnet
      interface. Analyzing both numerically and analytically the electric field of the
      SPPs at this interface, we corroborate our study with a proof-of-concept
      experiment showing efficient SPP-driven excitation of coherent spin precession
      with 0.41 THz frequency. We argue that the subdiffractional confinement of the
      SPP electric field enables strong spatial localization of the SPP-mediated
      excitation of spin dynamics. We demonstrate two orders of magnitude enhancement
      of the excitation efficiency at the surface plasmon resonance within a 100 nm
      layer of a dielectric garnet. Our findings broaden the horizons of ultrafast spin
      plasmonics and open pathways toward nonthermal opto-magnetic recording on the
      nanoscale.

PMID- 29641903
TI  - Molecular View of CO2 Capture by Polyethylenimine: Role of Structural and
      Dynamical Heterogeneity.
AB  - The molecular thermodynamics and kinetics of CO2 sorption in Polyethylenimine
      (PEI) melt have been investigated systematically using GCMC and MD simulations.
      We elucidate presence of significant structural and dynamic heterogeneity
      associated with the overall absorption process. CO2 adsorption in a PEI membrane
      shows a distinct two-stage process of a rapid CO2 adsorption at the interfaces
      (hundreds of picoseconds) followed by a significantly slower diffusion limited
      release toward the interior bulk regions of PEI melt (hundreds of nanoseconds to
      microseconds). The spatial heterogeneity of local structural features of the PEI
      chains lead to significantly heterogeneous absorption characterized by clustering
      and trapping of CO2 molecules that then lead to subdiffusive motion of CO2. In
      the complex interplay of interaction and entropy, the latter emerges out to be
      the major determining factor with significantly higher solubility of CO2 near the
      interfaces despite having lower density of binding amine groups. Regions having
      higher free-volume (entropically favorable) viz. interfaces, pores and loops
      demonstrate higher CO2 capture ability. Various local structural features of PEI
      conformations, for example, inter- and intrachain loops, pores of different
      radii, and di- or tricoordinated pores are explored for their effects on the
      varying CO2 adsorption abilities.

PMID- 29641904
TI  - Antifouling Properties of a Self-Assembling Glutamic Acid-Lysine Zwitterionic
      Polymer Surface Coating.
AB  - There is a need for the development of antifouling materials to resist adsorption
      of biomacromolecules. Here we describe the preparation of a novel zwitterionic
      block copolymer with the potential to prevent or delay the formation of microbial
      biofilms. The block copolymer comprised a zwitterionic (hydrophilic) section of
      alternating glutamic acid (negatively charged) and lysine (positively charged)
      units and a hydrophobic polystyrene section. Cryo-TEM and dynamic-light
      scattering (DLS) results showed that, on average, the block copolymer self
      assembled into 7-nm-diameter micelles in aqueous solutions (0 to 100 mM NaCl, pH
      6). Quartz crystal microbalance with dissipation monitoring (QCM-D), atomic force
      microscopy (AFM), and contact angle measurements demonstrated that the block
      copolymer self-assembled into a brush-like monolayer on polystyrene surfaces. The
      brush-like monolayer produced from a 100 mg/L block copolymer solution exhibited
      an average distance, d, of approximately 4-8 nm between each block copolymer
      molecule (center to center). Once the brush-like monolayer self-assembled, it
      reduced EPS adsorption onto the polystyrene surface by ~70% (mass), reduced the
      rate of bacterial attachment by >80%, and inhibited the development of thick
      biofilms. QCM-D results revealed that the EPS molecules penetrate between the
      chains of the brush and adsorb onto the polystyrene surface. Additionally, AFM
      analyses showed that the brush-like monolayer prevents the adhesion of large (>
      d) hydrophilic colloids onto the surface via hydration repulsion; however,
      molecules or colloids small enough to fit between the brush polymers (< d) were
      able to be adsorbed onto the surface via van der Waals interactions. Overall, we
      found that the penetration of extracellular organelles, as well as biopolymers
      through the brush, is critical for the failure of the antifouling coating, and
      likely could be prevented through tuning of the brush density. Stability and
      biofilm development testing on multiple surfaces (polypropylene, glass, and
      stainless steel) support practical applications of this novel block copolymer.

PMID- 29641905
TI  - Prostate-Specific Membrane Antigen Targeted Gold Nanoparticles for Theranostics
      of Prostate Cancer.
AB  - Prostate cancer is one of the most common cancers and among the leading causes of
      cancer deaths in the United States. Men diagnosed with the disease typically
      undergo radical prostatectomy, which often results in incontinence and impotence.
      Recurrence of the disease is often experienced by most patients with incomplete
      prostatectomy during surgery. Hence, the development of a technique that will
      enable surgeons to achieve a more precise prostatectomy remains an open
      challenge. In this contribution, we report a theranostic agent (AuNP-5kPEG-PSMA-1
      Pc4) based on prostate-specific membrane antigen (PSMA-1)-targeted gold
      nanoparticles (AuNPs) loaded with a fluorescent photodynamic therapy (PDT) drug,
      Pc4. The fabricated nanoparticles are well-characterized by spectroscopic and
      imaging techniques and are found to be stable over a wide range of solvents,
      buffers, and media. In vitro cellular uptake experiments demonstrated
      significantly higher nanoparticle uptake in PSMA-positive PC3pip cells than in
      PSMA-negative PC3flu cells. Further, more complete cell killing was observed in
      Pc3pip than in PC3flu cells upon exposure to light at different doses,
      demonstrating active targeting followed by Pc4 delivery. Likewise, in vivo
      studies showed remission on PSMA-expressing tumors 14 days post-PDT. Atomic
      absorption spectroscopy revealed that targeted AuNPs accumulate 4-fold higher in
      PC3pip than in PC3flu tumors. The nanoparticle system described herein is
      envisioned to provide surgical guidance for prostate tumor resection and
      therapeutic intervention when surgery is insufficient.

PMID- 29641906
TI  - Electrospun Polythiophene Phenylenes for Tissue Engineering.
AB  - This research focuses on the design of biocompatible materials/scaffold suitable
      for use for tissue engineering. Porous fiber mats were produced through
      electrospinning of polythiophene phenylene (PThP) conducting polymers blended
      with poly(lactide- co-glycolic acid) (PLGA). A peptide containing an
      arginylglycylaspartic acid (RGD) fragment was synthesized using solid phase
      peptide synthesis and subsequently grafted onto a PThP polymer using azide-alkyne
      "click" chemistry. The obtained RGD functionalized PThP was also electrospun into
      a fiber mat. The electrospun mats' morphology, roughness and stiffness were
      studied by means of scanning electron microscopy (SEM) and atomic force
      microscopy (AFM) and their electroactivity by cyclic voltammetry. The fibers show
      excellent cytocompatibility in culture assays with human dermal fibroblasts-adult
      (HDFa) and human epidermal melanocytes-adult (HEMa) cells. The electrospun
      fibers' roughness and stiffness changed after exposing the fiber mats to the cell
      culture medium (measured in dry state), but these changes did not affect the cell
      proliferation. The cytocompatibility of our porous scaffolds was established for
      their applicability as cell culture scaffolds by means of investigating
      mitochondrial activity of HDFa and HEMa cells on the scaffolds. The results
      revealed that the RGD moieties containing PThP scaffolds hold a promise in
      biomedical applications, including skin tissue engineering.

PMID- 29641907
TI  - Physiology and Engineering of the Graded Interfaces of Musculoskeletal Junctions.
AB  - The connective tissues of the musculoskeletal system can be grouped into fibrous,
      cartilaginous, and calcified tissues. While each tissue type has a distinct
      composition and function, the intersections between these tissues result in the
      formation of complex, composite, and graded junctions. The complexity of these
      interfaces is a critical aspect of their healthy function, but poses a
      significant challenge for their repair. In this review, we describe the
      organization and structure of complex musculoskeletal interfaces, identify
      emerging technologies for engineering such structures, and outline the
      requirements for assessing the complex nature of these tissues in the context of
      recapitulating their function through tissue engineering.

PMID- 29641908
TI  - Arterial Venous Differentiation for Vascular Bioengineering.
AB  - The development processes of arteries and veins are fundamentally different,
      leading to distinct differences in anatomy, structure, and function as well as
      molecular profiles. Understanding the complex interaction between genetic and
      epigenetic pathways, as well as extracellular and biomechanical signals that
      orchestrate arterial venous differentiation, is not only critical for the
      understanding of vascular diseases of arteries and veins but also valuable for
      vascular tissue engineering strategies. Recent research has suggested that
      certain transcriptional factors not only control arterial venous differentiation
      during development but also play a critical role in adult vessel function and
      disease processes. This review summarizes the signaling pathways and critical
      transcription factors that are important for arterial versus venous
      specification. We focus on those signals that have a direct relation to the
      structure and function of arteries and veins, and have implications for vascular
      disease processes and tissue engineering applications.

PMID- 29641909
TI  - The Ultrastructure, Spatial Distribution, and Osmium Tetroxide Binding of
      Lipofuscin and Melanosomes in Aging Monkey Retinal Epithelium.
AB  - PURPOSE: To examine the ultrastructure of lipofuscin bodies and melanosomes in
      retinal epithelium of elderly rhesus monkeys and determines changes in their
      number and morphology as a function of retinal eccentricity. METHODS: Electron
      microscopy was used to describe and quantify two major organelles in elderly
      monkey retinal epithelium, lipofuscin bodies and melanosomes, at different
      retinal loci extending from the macula to the peri-macula, equator, periphery and
      ora serrata. Osmium tetroxide was used to distinguish lipofuscin bodies from
      melanosomes. RESULTS: Lipofuscin bodies and melanosomes diminished in number with
      advanced age but there was an inverse relationship between these two organelles.
      Lipofuscin bodies were more numerous in the macula and melanosomes more numerous
      in the peripheral retina. Three types of lipofuscin bodies were identified: 1)
      smaller and tending to locate in the middle third of the epithelial cell, 2)
      larger, less common, and located more basally, and 3) extremely rare, melano
      lipofuscin, containing a melanosome. When osmicated, all lipofuscin bodies
      contained electron dense materials. When osmium tetroxide was not used for
      fixation, the first two types of lipofuscin bodies lost their electron densities
      while the third type retained its electron density due to the melanosome it
      contained. CONCLUSION: As previously reported for human retina, lipofuscin is
      most abundant in the macular and peri-macular epithelium and least abundant in
      the periphery, whereas melanosomes show the opposite relationship. This
      distribution pattern could contribute to the macula's greater vulnerability to
      photo-toxicity. Three types of lipofuscin bodies are found in aging monkey
      retinal epithelium. All types contain electron dense material, but the most
      prominent two types lose their densities in the absence of osmium tetroxide
      during fixation. Most of the electron densities in lipofuscin bodies must contain
      a material that binds strongly to osmium tetroxide such as polyunsaturated fatty
      acids.

PMID- 29641910
TI  - Neurosocialities: Anthropological Engagements with the Neurosciences.

PMID- 29641911
TI  - Sickle Cell Anemia and Its Phenotypes.
AB  - In the 100 years since sickle cell anemia (SCA) was first described in the
      medical literature, studies of its molecular and pathophysiological basis have
      been at the vanguard of scientific discovery. By contrast, the translation of
      such knowledge into treatments that improve the lives of those affected has been
      much too slow. Recent years, however, have seen major advances on several fronts.
      A more detailed understanding of the switch from fetal to adult hemoglobin and
      the identification of regulators such as BCL11A provide hope that these findings
      will be translated into genomic-based approaches to the therapeutic reactivation
      of hemoglobin F production in patients with SCA. Meanwhile, an unprecedented
      number of new drugs aimed at both the treatment and prevention of end-organ
      damage are now in the pipeline, outcomes from potentially curative treatments
      such as allogeneic hematopoietic stem cell transplantation are improving, and
      great strides are being made in gene therapy, where methods employing both
      antisickling beta-globin lentiviral vectors and gene editing are now entering
      clinical trials. Encouragingly, after a century of neglect, the profile of the
      vast majority of those with SCA in Africa and India is also finally improving.

PMID- 29641912
TI  - Using Full Genomic Information to Predict Disease: Breaking Down the Barriers
      Between Complex and Mendelian Diseases.
AB  - While sequence-based genetic tests have long been available for specific loci,
      especially for Mendelian disease, the rapidly falling costs of genome-wide
      genotyping arrays, whole-exome sequencing, and whole-genome sequencing are moving
      us toward a future where full genomic information might inform the prognosis and
      treatment of a variety of diseases, including complex disease. Similarly, the
      availability of large populations with full genomic information has enabled new
      insights about the etiology and genetic architecture of complex disease. Insights
      from the latest generation of genomic studies suggest that our categorization of
      diseases as complex may conceal a wide spectrum of genetic architectures and
      causal mechanisms that ranges from Mendelian forms of complex disease to complex
      regulatory structures underlying Mendelian disease. Here, we review these
      insights, along with advances in the prediction of disease risk and outcomes from
      full genomic information.

PMID- 29641913
TI  - Healthy obesity: time to give up the ghost?

PMID- 29641915
TI  - Microkinetic Analysis and Scaling Relations for Catalyst Design.
AB  - Microkinetic analysis plays an important role in catalyst design because it
      provides insight into the fundamental surface chemistry that controls catalyst
      performance. In this review, we summarize the development of microkinetic models
      and the inclusion of scaling relationships in these models. We discuss the
      importance of achieving stoichiometric and thermodynamic consistency in
      developing microkinetic models. We also outline how analysis of the maximum rates
      of elementary steps can be used to determine which transition states and adsorbed
      intermediates are kinetically significant, allowing the derivation of general
      reaction kinetics rate expressions in terms of changes in binding energies of the
      relevant transition states and intermediates. Through these analyses, we present
      how to predict optimal surface coverages and binding energies of adsorbed
      species, as well as the extent of potential rate improvement for a catalytic
      system. For systems in which the extent of potential rate improvement is small
      because of limitations imposed by scaling relations, different approaches,
      including the addition of promoters and formation of catalysts containing
      multiple functionalities, can be used to break the scaling relations and obtain
      further rate enhancement.

PMID- 29641914
TI  - Retinal pH and Acid Regulation During Metabolic Acidosis.
AB  - PURPOSE: Changes in retinal pH may contribute to a variety of eye diseases. To
      study the effect of acidosis alone, we induced systemic metabolic acidosis and
      hypothesized that the retina would respond with altered expression of genes
      involved in acid/base regulation. METHODS: Systemic metabolic acidosis was
      induced in Long-Evans rats for up to 2 weeks by adding NH4Cl to the drinking
      water. After 2 weeks, venous pH was 7.25 +/- 0.08 (SD) and [HCO3-] was 21.4 +/-
      4.6 mM in acidotic animals; pH was 7.41 +/- 0.03 and [HCO3-] was 30.5 +/- 1.0 mM
      in controls. Retinal mRNAs were quantified by quantitative reverse transcription
      polymerase chain reaction. Protein was quantified with Western blots and
      localized by confocal microscopy. Retinal [H+]o was measured in vivo with pH
      microelectrodes in animals subjected to metabolic acidosis and in controls.
      RESULTS: NH4Cl in drinking water or given intravenous was effective in acidifying
      the retina. Cariporide, a blocker of Na+/H+ exchange, further acidified the
      retina. Metabolic acidosis for 2 weeks led to increases of 40-100% in mRNA for
      carbonic anhydrase isoforms II (CA-II) and XIV (CA-XIV) and acid-sensing ion
      channels 1 and 4 (ASIC1 and ASIC4) (all p < 0.005). Expression of anion exchange
      protein 3 (AEP-3) and Na+/H+ exchanger (NHE)-1 also increased by >=50% (both p <
      0.0001). Changes were similar after 1 week of acidosis. Protein for AEP-3
      doubled. NHE-1 co-localized with vascular markers, particularly in the outer
      plexiform layer. CA-II was located in the neural parenchyma of the ganglion cell
      layer and diffusely in the rest of the inner retina. CONCLUSIONS: The retina
      responds to systemic acidosis with increased expression of proton and bicarbonate
      exchangers, carbonic anhydrase, and ASICs. While responses to acidosis are
      usually associated with renal regulation, these studies suggest that the retina
      responds to changes in local pH presumably to control its acid/base environment
      in response to systemic acidosis.

PMID- 29641917
TI  - Terminalia ferdinandiana Exell. Fruit and Leaf Extracts Inhibit Proliferation and
      Induce Apoptosis in Selected Human Cancer Cell Lines.
AB  - Terminalia spp. are characterized by their high antioxidant contents and several
      species have anticancer activity. This study examined T. ferdinandiana fruit and
      leaf extracts for antiproliferative and apoptotic activities against a panel of
      human carcinoma cell lines. All extracts inhibited Caco2, HeLa, Jeg-3, JAR, MC3T3
      E1, and MG63 proliferation. The leaf ethyl acetate extract was the most potent
      inhibitor of proliferation (MC3T3-E1 IC50 = of 6 ug/ml; Caco2 IC50 = 102 ug/ml).
      Furthermore, IC50's < 500 ug/ml were determined against all cell lines tested
      against that extract. The methanolic leaf extract was also a potent inhibitor of
      cell proliferation (Jeg-3 IC50 = 147 ug/ml; MC3T3-E1 IC50 = 40 ug/ml). The fruit
      extracts were also good inhibitors of carcinoma cell proliferation. Cell imaging
      studies detected morphological features consistent with apoptosis in Caco2 cells
      exposed to the ethyl acetate, methanolic, and aqueous extracts. Caspase 3
      activity was significantly elevated in Caco2 cells exposed to these extracts,
      indicating that apoptosis was induced. The leaf ethyl acetate extract contained a
      high diversity and relative abundance of tannins and flavonoids. All T.
      ferdinandiana fruit and leaf extracts displayed either no toxic or low toxicity
      in the Artemia franciscana bioassay and in a HDF viability assay.

PMID- 29641916
TI  - Platelet-Activating Factor (PAF) Receptor Antagonism Modulates Inflammatory
      Signaling in Experimental Uveitis.
AB  - BACKGROUND: The phospholipid mediator platelet-activating factor (PAF) activates
      an inflammatory response that includes arachidonic acid release and prostaglandin
      production in the eye, increasing vascular permeability and inflammation. The
      purpose of this study is to investigate the action of LAU-0901, a novel PAF
      receptor antagonist, on experimental uveitis. METHODS: Uveitis was induced in
      Lewis rats by lipopolysaccharide treatment. LAU-0901 was then delivered
      systemically in different concentrations at plus 4 and 16 hours, or vehicle
      injected as controls. Additional animals were used for histological analyses of
      untreated, uveitis, and uveitis-plus-LAU-0901 retinas. Conventional histological
      and immunohistochemical methods were employed. A slit lamp and Spectral Domain
      Ocular Coherence Tomography (SD-OCT) retinal imager was used for anterior segment
      photography and posterior pole OCT. Rats were euthanized 4 hours after the second
      LAU-0901 injection in this 24-hour model. Aqueous humor was collected and
      quantified, and also analyzed for tumor necrosis factor alpha (TNF-alpha).
      RESULTS: Uveitic eyes demonstrated hypopyon formation, leukocyte infiltration,
      and an increase in aqueous protein and TNF-alpha levels. LAU-0901 treatment
      resulted in a dose-dependent reduction in inflammation, reflected by reduced
      total protein levels (up to a 64% reduction). Moreover, hypopyon was prevented,
      leukocytes were absent in vitreous and aqueous humor, and TNF-alpha levels were
      reduced by 91%. CONCLUSIONS: The PAF receptor antagonist LAU-0901 decreases
      ocular inflammation in a rat model of anterior uveitis in a dose-dependent
      manner, suggesting that use of this molecule may provide a means to attenuate
      inflammation onset and offer a future alternative or adjunctive treatment for
      ocular inflammation.

PMID- 29641918
TI  - Fast Growth of Immature Brood in a Social Parasite Wasp: A Convergent Evolution
      between Avian and Insect Cuckoos.
AB  - Studies on avian cuckoos have demonstrated that parasite chicks compete with host
      fledglings to monopolize food or manipulate the foster parents to increase their
      provisioning rate. This topic has never been explicitly investigated in insect
      social parasites, which use the social system of another species to raise their
      brood. Here we show that the immature brood of the cuckoo wasp Polistes sulcifer
      grows more rapidly than the host immature brood. Host workers perform more
      parental care to parasite larvae than to conspecific ones. Thus, the rapid growth
      of the parasite larvae is evidently due to increased host care, which prolongs
      the development of host larvae reared in the same colony. We suggest that
      parasite larvae play an active role in host exploitation through manipulation of
      host workers, as occurs in parasitic birds.

PMID- 29641919
TI  - Size and the Not-So-Single Sex: Disentangling the Effects of Size and Budget on
      Sex Allocation in Hermaphrodites.
AB  - Sex allocation theory explains how size-related variations in male and female
      fitness may favor the evolution of size-dependent sex allocation in
      hermaphrodites. Although empirical studies show that sex allocation changes
      gradually with size in many species, theoretical studies tend to predict an
      abrupt sex reversal from one sex to the other, that is, single-sexed sequential
      hermaphrodites. We show that this discrepancy between data and theory collapses
      if one takes into account that size affects male and female fitness through
      distinct routes. Using the classification of budget (larger individuals spend a
      greater budget on reproduction) and direct (e.g., larger plants are taller and
      may disperse pollen more efficiently) effects of size suggested by Klinkhamer et
      al., we propose a simple general framework appropriately incorporating these two
      categories of size effects in male and female fitness expressions. Analytical and
      numerical results show that a gradual sex change is evolutionarily stable for a
      large set of parameter values. Sex reversal is selected only in the absence of
      budget effects of size. We provide further predictions on size-dependent sex
      allocation and assess the relative importance of budget and direct effect for
      creating different patterns.

PMID- 29641920
TI  - Cooperation and Punishment, Especially in Humans.
AB  - Explaining altruistic cooperation is one of the greatest challenges faced by
      sociologists, economists, and evolutionary biologists. The problem is determining
      why an individual would carry out a costly behavior that benefits another.
      Possible solutions to this problem include kinship, repeated interactions, and
      policing. Another solution that has recently received much attention is the
      threat of punishment. However, punishing behavior is often costly for the
      punisher, and so it is not immediately clear how costly punishment could evolve.
      We use a direct (neighbor-modulated) fitness approach to analyze when punishment
      is favored. This methodology reveals that, contrary to previous suggestions,
      relatedness between interacting individuals is not crucial to explaining
      cooperation through punishment. In fact, increasing relatedness directly
      disfavors punishing behavior. Instead, the crucial factor is a positive
      correlation between the punishment strategy of an individual and the cooperation
      it receives. This could arise in several ways, such as when facultative
      adjustment of behavior leads individuals to cooperate more when interacting with
      individuals who are more likely to punish. More generally, our results provide a
      clear example of how the fundamental factor driving the evolution of social
      traits is a correlation between social partners and how this can arise for
      reasons other than genealogical kinship.

PMID- 29641921
TI  - Morphological and Physiological Correlates of Hybrid Parthenogenesis.
AB  - Asexuality frequently evolves in association with hybridity and polyploidy. The
      phenotypic consequences of this association must be understood before we can
      fully appreciate the reason for the short-term success, and the long-term
      failure, of asexual genetic systems. Parthenogenetic forms within the Australian
      gecko complex Heteronotia binoei are triploid hybrids and overlap geographically
      with both of their parental taxa as well as another sexual lineage. We compared
      nine morphological and nine physiological traits in wild-caught adult sexual and
      asexual individuals as well as their captive-bred progeny across a 1,200-km
      latitudinal gradient. Genome dosage effects were apparent in that the
      parthenogens were most phenotypically similar to the parental form for which they
      had a double dosage. Physiological differences between parthenogens and sexuals
      were often in the opposite direction of that expected under heterosis. Sympatric
      populations of sexual and parthenogenetic H. binoei differ in ecologically
      significant phenotypic traits, possibly reducing niche overlap. In keeping with
      the Red Queen hypothesis, parthenogenetic H. binoei had more ectoparasitic mites
      than did sexuals in some regions. Lizards with high mite loads also had high
      rates of evaporative water loss, suggesting a direct link between phenotypic
      traits and vulnerability to parasites.

PMID- 29641922
TI  - Trade-Off Geometries and Frequency-Dependent Selection.
AB  - Life-history evolution is determined by the interplay between natural selection
      and adaptive constraints. The classical approach to studying constrained life
      history evolution-Richard Levins's geometric comparison of fitness sets and
      adaptive functions-is applicable when selection pressures are frequency
      independent. Here we extend this widely used tool to frequency-dependent
      selection. Such selection pressures vary with a population's phenotypic
      composition and are increasingly recognized as ubiquitous. Under frequency
      dependence, two independent properties have to be distinguished: evolutionary
      stability (an evolutionarily stable strategy cannot be invaded once established)
      and convergence stability (only a convergence stable strategy can be attained
      through small, selectively advantageous steps). Combination of both properties
      results in four classes of possible evolutionary outcomes. We introduce a
      geometric mode of analysis that enables predicting, for any bivariate selection
      problem, evolutionary outcomes induced by trade-offs of given shape, shapes of
      trade-offs required for given evolutionary outcomes, the set of all evolutionary
      outcomes trade-offs can induce, and effects of ecological parameters on
      evolutionary outcomes independent of trade-off shape.

PMID- 29641923
TI  - Detection of Fruit and the Selection of Primate Visual Pigments for Color Vision.
AB  - Primates have X chromosome genes for cone photopigments with sensitivity maxima
      from 535 to 562 nm. Old World monkeys and apes (catarrhines) and the New World
      (platyrrhine) genus Alouatta have separate genes for 535-nm (medium wavelength;
      M) and 562-nm (long wavelength; L) pigments. These pigments, together with a 425
      nm (short wavelength) pigment, permit trichromatic color vision. Other
      platyrrhines and prosimians have a single X chromosome gene but often with
      alleles for two or three M/L photopigments. Consequently, heterozygote females
      are trichromats, but males and homozygote females are dichromats. The criteria
      that affect the evolution of M/L alleles and maintain genetic polymorphism remain
      a puzzle, but selection for finding food may be important. We compare different
      types of color vision for detecting more than 100 plant species consumed by
      tamarins (Saguinus spp.) in Peru. There is evidence that both frequency-dependent
      selection on homozygotes and heterozygote advantage favor M/L polymorphism and
      that trichromatic color vision is most advantageous in dim light. Also, whereas
      the 562-nm allele is present in all species, the occurrence of 535- to 556-nm
      alleles varies between species. This variation probably arises because
      trichromatic color vision favors widely separated pigments and equal frequencies
      of 535/543- and 562-nm alleles, whereas in dichromats, long-wavelength pigment
      alleles are fitter.

PMID- 29641924
TI  - Bergmann's Clines in Ectotherms: Illustrating a Life-History Perspective with
      Sceloporine Lizards.
AB  - The generality and causes of Bergmann's rule have been debated vigorously in the
      last few years, but Bergmann's clines are rarely explained in the context of life
      history theory. We used both traditional and phylogenetic comparative analyses to
      explore the causes of latitudinal and thermal clines in the body size of the
      eastern fence lizard (Sceloporus undulatus). The proximate mechanism for larger
      body sizes in colder environments is delayed maturation, which results in a
      greater fecundity but a lower survival to maturity. Life-history theory predicts
      that a higher survivorship of juveniles in colder environments can favor the
      evolution of a Bergmann's cline. Consistent with this theory, lizards in colder
      environments survive better as juveniles and delay maturation until reaching a
      larger body size than that of lizards in warmer environments. We expect similar
      relationships among temperature, survivorship, and age/size at maturity exist in
      other ectotherms that exhibit Bergmann's clines. However, life-history traits of
      S. undulatus were more strongly related to latitude than they were to
      temperature, indicating that both abiotic and biotic factors should be considered
      as causes of Bergmann's clines. Nonetheless, analyses of the costs and benefits
      of particular body sizes in different thermal environments will enhance our
      understanding of geographic variation.

PMID- 29641925
TI  - When Resistance Is Useless: Policing and the Evolution of Reproductive
      Acquiescence in Insect Societies.
AB  - In social groups composed of kin, inclusive fitness benefits can favor greater
      cooperation. Alternatively, cooperation can be enforced through the policing of
      less cooperative individuals. Here, we show that the effect of policing can be
      twofold: not only can it directly suppress individual selfishness, it can also
      entirely remove the incentive for individuals to act selfishly in the first
      place. We term such individual restraint in response to socially imposed policing
      "acquiescence" and illustrate the concept using examples drawn from the social
      Hymenoptera (the ants, bees, and wasps). Inclusive fitness models confirm that
      when a policing system is in place, individuals should be less tempted to act
      selfishly. This is shown to have important consequences for the resolution of
      conflict within their societies. For example, it can explain why in many species
      very few workers attempt to reproduce and why immature females usually do not
      attempt to develop as queens rather than workers. Although our analyses are
      primarily focused on the social insects, our conclusions are likely to be general
      and to apply to other societies as well.

PMID- 29641926
TI  - Consequences of Intraspecific Competition and Environmental Variation for
      Selection in the Mustard Sinapsis arvensis: Contrasting Ecological and
      Evolutionary Perspectives.
AB  - Alternative models of plant life-history evolution differ in their views of how
      abiotic stress and competition interact to shape the evolution of plant life
      history traits. To address this debate, which crosses traditional boundaries
      between community ecology and population biology, we grew wild turnip families
      from three selection histories in a field experiment in which we manipulated
      conspecific density and sun exposure. Hot spring conditions caused neutral
      shading to reduce drought stress, resulting in a greater mean and variance for
      lifetime fertility at low density and greater intensity of competition at high
      density. The variance in relative fitness among individuals or families was least
      in partial shade at low density. Prior selection under shade stress in the
      greenhouse reduced lifetime fitness in the less stressful partial-shade treatment
      under field conditions. Patterns of selection and predicted trait evolution were
      more similar between high and low densities than between the two light
      environments. Partial shade favored the proliferation of large leaves early in
      development, especially at high density. Selection in the stressful full-sun
      treatment favored reduced pathogen susceptibility at both densities and early
      flowering at low density. Because direct selection on traits changed principally
      in magnitude rather than in direction, genetic correlations for fitness were
      generally positive between light and density treatments. Greater intraspecific
      competition led to more rapid predicted trait evolution in the partial-shade
      environment but not in the stressful full-sun treatment.

PMID- 29641927
TI  - Clustering due to Acceleration in the Response to Population Gradient: A Simple
      Self-Organization Model.
AB  - We explore the phenomenon of animal self-organization due to autotaxis, that is,
      the movement of individuals induced by their own density gradient. There is
      natural evidence that clustering occurs as a result of the interplay between
      random and directed movements of individuals due to mutual attraction and
      repulsion. Classically, it is assumed that taxis velocity is determined by the
      density gradient of some stimulus. However, it is known that partial differential
      equation (PDE) diffusion-advection models that rest on this assumption cannot
      give a realistic representation of a stationary or moving cohesive group of
      individuals with a uniform interior density and sharp edges. Pioneering work by
      Okubo and coworkers suggests that the acceleration of individuals (rather than
      their velocity directly) is proportional to the population density gradient. A
      PDE model resting on this finding was constructed and investigated. The model
      demonstrates the formation of steady heterogeneous structures of the required
      shape. This feature can be interpreted as dynamic self-organization, like fish
      shoaling or insect swarming. This model is the first to achieve this result while
      considering an autonomous population in a simple PDE framework. Analytical and
      numerical studies show that the link between the acceleration and the density
      gradient is crucial for the appearance of clusters.

PMID- 29641928
TI  - Phylogenetic Comparative Analysis: A Modeling Approach for Adaptive Evolution.
AB  - Biologists employ phylogenetic comparative methods to study adaptive evolution.
      However, none of the popular methods model selection directly. We explain and
      develop a method based on the Ornstein-Uhlenbeck (OU) process, first proposed by
      Hansen. Ornstein-Uhlenbeck models incorporate both selection and drift and are
      thus qualitatively different from, and more general than, pure drift models based
      on Brownian motion. Most importantly, OU models possess selective optima that
      formalize the notion of adaptive zone. In this article, we develop the method for
      one quantitative character, discuss interpretations of its parameters, and
      provide code implementing the method. Our approach allows us to translate
      hypotheses regarding adaptation in different selective regimes into explicit
      models, to test the models against data using maximum-likelihood-based model
      selection techniques, and to infer details of the evolutionary process. We
      illustrate the method using two worked examples. Relative to existing approaches,
      the direct modeling approach we demonstrate allows one to explore more detailed
      hypotheses and to utilize more of the information content of comparative data
      sets than existing methods. Moreover, the use of a model selection framework to
      simultaneously compare a variety of hypotheses advances our ability to assess
      alternative evolutionary explanations.

PMID- 29641929
TI  - The Relationship of Phylogeny to Community Structure: The Cactus Yeast Community.
AB  - Species abundances are important properties of ecological communities.
      Theoretical debate has arisen over whether communities are governed by assembly
      rules. Some ecologists have suggested that community organization depends on the
      phylogenetic relatedness of its interacting members. This postulate has not been
      adequately tested primarily because molecular phylogenies for entire communities
      are rare. We use the molecular phylogeny and species abundances from the well
      studied yeasts that live in decaying cactus tissue (i.e., cactus yeast community)
      to demonstrate that community structure is indeed linked to genetic relatedness
      but that the relationship is different for the same yeasts found in hosts of two
      subfamilies of the Cactaceae. In the Opuntia cacti, the genetically related and
      unrelated yeasts have equivalent probability of being similar in abundance.
      Conversely, in the columnar cacti, the abundant yeast species tend to be
      genetically distant from one another, whereas the rare species tend to be closely
      related. The distinctive biochemical differences between the Opuntia and columnar
      cacti habitats suggest that conditions imposed by the environment modify the
      relationship between phylogenetic relatedness and species abundances in the
      cactus yeast community.

PMID- 29641930
TI  - Life-History Variation Predicts the Effects of Demographic Stochasticity on Avian
      Population Dynamics.
AB  - Comparative analyses of avian population fluctuations have shown large
      interspecific differences in population variability that have been difficult to
      relate to variation in general ecological characteristics. Here we show that
      interspecific variation in demographic stochasticity, caused by random variation
      among individuals in their fitness contributions, can be predicted from a
      knowledge of the species' position along a "slow-fast" gradient of life-history
      variation, ranging from high reproductive species with short life expectancy at
      one end to species that often produce a single offspring but survive well at the
      other end of the continuum. The demographic stochasticity decreased with adult
      survival rate, age at maturity, and generation time or the position of the
      species toward the slow end of the slow-fast life-history gradient. This
      relationship between life-history characteristics and demographic stochasticity
      was related to interspecific differences in the variation among females in
      recruitment as well as to differences in the individual variation in survival.
      Because reproductive decisions in birds are often subject to strong natural
      selection, our results provide strong evidence for adaptive modifications of
      reproductive investment through life-history evolution of the influence of
      stochastic variation on avian population dynamics.

PMID- 29641931
TI  - An Italian cost-effectiveness analysis of paclitaxel albumin (nab-paclitaxel) +
      gemcitabine vs gemcitabine alone for metastatic pancreatic cancer patients: the
      APICE study.
AB  - BACKGROUND: the APICE study evaluates the cost-effectiveness of nanoparticle
      albumin-bound paclitaxel (nab-paclitaxel - Nab-P) + gemcitabine (G) vs G alone in
      metastatic pancreatic cancer (MPC) from the Italian National Health Service
      (INHS) standpoint. RESEARCH DESIGN AND METHODS: A 4-year, 4 health states
      (progression-free; progressed; end of life; death) Markov model based on the
      MPACT trial was developed to estimate costs (Euro [?], 2017 values), and quality
      adjusted life years (QALYs). Patients were assumed to receive intravenously Nab-P
      125 mg/m2 + G 1000 mg/m2 on days 1, 8, and 15 every 4 weeks or G alone 1000 mg/m2
      weekly for 7 out of 8 weeks (cycle 1) and then on days 1, 8, and 15 every 4 weeks
      (cycle 2 and subsequent cycles) until progression. One-way and probabilistic
      sensitivity analyses explored the uncertainty surrounding the baseline
      incremental cost-utility ratio (ICUR). RESULTS: Nab-P + G totals 0.154
      incremental QALYs and ?7082.68 incremental costs vs G alone. ICUR (?46,021.58) is
      lower than the informal threshold value of ?87,330 adopted by the Italian
      Medicines Agency during 2010-2013 for reimbursing oncological drugs. Sensitivity
      analyses confirmed the robustness of the baseline findings. CONCLUSIONS: Nab-P +
      G in MPC patients can be considered cost-effective for the INHS.

PMID- 29641932
TI  - Identification and characterization of amiodarone metabolites in rats using UPLC
      ESI-QTOFMS-based untargeted metabolomics approach.
AB  - Amiodarone is a class III anti-arrhythmic benzofuran derivative extensively
      utilized in treatment of life-threatening ventricular and supraventricular
      arrhythmias. However, amiodarone also produces adverse side effects including
      liver injury due to its metabolites rather than parent drug. The purpose of the
      present study was to identify metabolites of amiodarone in the plasma and urine
      of rats administered the drug by using an untargeted metabolomics approach. Drug
      metabolites were profiled by ultra-performance liquid chromatography-linked
      electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI
      QTOFMS) and results subjected to multivariate data analysis. A total of 49
      amiodarone metabolites were identified and their structures were characterized by
      tandem mass spectrometry. Amiodarone metabolites are presumed to be generated via
      five major types of metabolic reactions including N-desethylation, hydroxylation,
      carboxylation (oxo/hydroxylation), de-iodination, and glucuronidation. Data
      demonstrated that an untargeted metabolomics approach appeared to be a reliable
      tool for identifying unknown metabolites in a complex biological matrix.

PMID- 29641934
TI  - The challenge of establishing treatment efficacy for cutaneous vascular
      manifestations of systemic sclerosis.
AB  - INTRODUCTION: The cutaneous vascular manifestations of systemic sclerosis (SSc)
      comprise Raynaud's phenomenon, cutaneous ulceration, telangiectasia formation and
      critical digital ischaemia; each of which are associated with significant disease
      related morbidity. Despite the availability of multiple classes of vasodilator
      therapy, many of which have been the subject of RCTs, a limited number of
      pharmacological interventions are currently approved for the management of
      cutaneous vascular manifestations of SSc. Areas covered: A major challenge has
      been demonstrating treatment efficacy with examples of promising therapies
      yielding contrasting results in controlled trial settings. Differences between
      consensus best-practice guidelines, evidence-based recommendations and marketing
      approvals in different jurisdictions has resulted in geographic variation in
      clinical practice concerning the management of cutaneous vascular manifestations
      of SSc. Difficulty demonstrating treatment efficacy risks waning industry
      engagement for drug development programmes in this field. This article highlights
      the key challenges in establishing treatment efficacy and barriers that must be
      overcome to support successful clinical trial programmes across the spectrum of
      cutaneous vascular manifestations of SSc. Expert commentary: The paucity of
      approved treatments for cutaneous vascular manifestations of SSc relates as much
      to challenges in clinical trial design and the need for reliable clinical trial
      endpoints, as to lack of therapeutic options.

PMID- 29641935
TI  - Effect of Botulinum Toxin A Treatment on Eyelid Pressure in Eyes with
      Blepharospasm.
AB  - OBJECTIVE: To determine the effect of botulinum toxin A (BTX-A) on the eyelid
      pressure in patients with benign essential blepharospasm (BEB). METHODS: Twenty
      normal volunteers (10 men, 10 women; average age 59.7 +/- 11.3 years) and 33
      patients (12 men, 21 women; average age 61.1 +/- 14.7 years) with BEB were
      studied. The upper and lower eyelid pressures were measured with a blepharo
      tensiometer in the normal subjects (N group). The eyelid pressures and
      intraocular pressures (IOP) were measured before and after the BTX-A injections
      in the BEB patients (B group). RESULTS: The mean eyelid pressure in the N group
      was 31.0 +/- 6.8 mmHg for the upper eyelid and 29.9 +/- 6.5 mmHg for the lower
      eyelid (P > 0.05). The mean eyelid pressure in the B group before treatment was
      35.3 +/- 7.0 mmHg for the upper eyelid and 37.8 +/- 6.6 mmHg for the lower
      eyelid. The eyelid pressure in the B group was significantly higher than in the N
      group for the upper and lower eyelids (both P < 0.001). The eyelid pressure was
      significantly decreased after BTX-A treatment for the upper (29.9 +/- 7.5 mmHg)
      and the lower (32.8 +/- 7.0 mmHg) eyelids (both P < 0.001). The mean IOP was 15.1
      +/- 2.9 mmHg before, and it significantly decreased to 14.5 +/- 2.8 mmHg (P =
      0.020) after the BTX-A injections. The IOP was significantly correlated with the
      lower eyelid pressure (P = 0.0435), but not with the upper eyelid pressure (P =
      0.175). CONCLUSION: The eyelid pressure was higher in the patients with BEB. The
      eyelid pressure and the IOP were significantly reduced after the BTX-A
      injections. In addition, the IOPs were significantly correlated with the eyelid
      pressure of the lower eyelid.

PMID- 29641933
TI  - Arsenic association with circulating oxidized low-density lipoprotein in a Native
      American community.
AB  - More than 500 abandoned uranium (U) mines within the Navajo Nation contribute U,
      arsenic (As) and other metals to groundwater, soil and potentially air through
      airborne transport. The adverse cardiovascular health effects attributed to
      cumulative exposure to these metals remains uncertain. The aim of this study was
      to examine whether environmental exposure to these metals may promote or
      exacerbate the oxidation of low-density lipoprotein (LDL) cholesterol in this
      Native American population. The correlation of cardiovascular biomarkers
      (oxidized LDL (oxLDL) and C-reactive protein (CRP)) from a Navajo cohort (n =
      252) with mean annual As and U intakes from water and urine metals was estimated
      using linear regression. Proof-of-concept assays were performed to investigate
      whether As and U directly oxidize human LDL. Mean annual As intake from water was
      positively and significantly associated with oxLDL, but not CRP in this study
      population, while U intake estimates were negatively associated with oxLDL. In an
      acellular system, As, but not U, directly oxidized the apolipoprotein B-100
      component of purified human LDL. Neither metal promoted lipid peroxidation of the
      LDL particle. Both the population and lab results are consistent with the
      hypothesis that As promotes oxidation of LDL, a crucial step in vascular
      inflammation and chronic vascular disease. Conversely, for outcomes related to U,
      negative associations were observed between U intake and oxLDL, and U only
      minimally altered human LDL in direct exposure experiments. Only urine U was
      correlated with CRP, whereas no other metals in water or urine were apparently
      reliable predictors of this inflammatory marker.

PMID- 29641936
TI  - Transcranial direct current stimulation (tDCS) targeting the left inferior
      frontal gyrus: Effects on creativity across cultures.
AB  - Although evidence points to the existence of cultural differences in creativity,
      the mechanisms that underlie these differences are largely unknown. The twofold
      model of creativity posits two recursive stages: a generation phase and an
      evaluation phase. Considering that recent studies suggest that the left inferior
      frontal gyrus) L-IFG(may inhibit creativity during the evaluation phase, we
      hypothesized that manipulating IFG activity would affect participants' level of
      creativity. We further predicted that the IFG may be "hyperactive" in a culture
      that typically discourages uniqueness (e.g., Japan) as compared to a Western
      culture (e.g., Israel); therefore the effect of inhibiting the L-IFG was expected
      to be higher in Japanese. To support this hypothesis we altered L-IFG activation
      using tDCS (transcranial direct current stimulation) in 30 Japanese and 30
      Israeli participants and examined the effect of anodal and cathodal stimulation
      on divergent thinking (DT). Regardless of culture, cathodal stimulation increased
      creativity compared to sham, while anodal stimulation diminished creativity.
      Although cultural differences were found in DT scores, stimulation had no
      differential effect between the cultures. Taken together, the results confirm
      that the L-IFG plays a key role in creativity across cultures. The null findings
      regarding the expected interaction between stimulation and culture are discussed.

PMID- 29641937
TI  - To diagnose or not to diagnose? Timing is the question: balancing early diagnosis
      of multiple sclerosis with misdiagnosis.

PMID- 29641939
TI  - Medulloblastoma: From Molecular Subgroups to Molecular Targeted Therapies.
AB  - Brain tumors are the leading cause of cancer-related death in children, and
      medulloblastoma (MB) is the most common malignant pediatric brain tumor. Advances
      in surgery, radiation, and chemotherapy have improved the survival of MB
      patients. But despite these advances, 25-30% of patients still die from the
      disease, and survivors suffer severe long-term side effects from the aggressive
      therapies they receive. Although MB is often considered a single disease,
      molecular profiling has revealed a significant degree of heterogeneity, and there
      is a growing consensus that MB consists of multiple subgroups with distinct
      driver mutations, cells of origin, and prognosis. Here, we review recent progress
      in MB research, with a focus on the genes and pathways that drive tumorigenesis,
      the animal models that have been developed to study tumor biology, and the
      advances in conventional and targeted therapy.

PMID- 29641938
TI  - In Vivo Imaging of the Retina, Choroid, and Optic Nerve Head in Guinea Pigs.
AB  - PURPOSE: Guinea pigs are increasingly being used as a model of myopia, and may
      also represent a novel model of glaucoma. Here, optical coherence tomography
      (OCT) imaging was performed in guinea pigs. In vivo measurements of retinal,
      choroidal, and optic nerve head parameters were compared with histology, and
      repeatability and interocular variations were assessed. METHODS: OCT imaging and
      histology were performed on adult guinea pigs (n = 9). Using a custom program in
      MATLAB, total retina, ganglion cell/nerve fiber layer (GC/NFL), outer retina, and
      choroid thicknesses were determined. Additionally, Bruch's membrane opening (BMO)
      area and diameter, and minimum rim width were calculated. Intraobserver,
      interocular, and intersession coefficients of variation (CV) and intraclass
      correlation coefficients (ICC) were assessed. RESULTS: Retina, GC/NFL, outer
      retina and choroid thicknesses from in vivo OCT imaging were 147.7 +/- 5.8 MUm,
      59.2 +/- 4.5 MUm, 72.4 +/- 2.4 MUm, and 64.8 +/- 11.6 MUm, respectively.
      Interocular CV ranged from 1.8% to 11% (paired t-test, p = 0.16 to 0.81), and
      intersession CV ranged from 1.1% to 5.6% (p = 0.12 to 0.82), with the choroid
      showing the greatest variability. BMO area was 0.192 +/- 0.023 mm2, and diameter
      was 493.79 +/- 31.89 MUm, with intersession CV of 3.3% and 1.7%, respectively.
      Hyper reflective retinal layers in OCT correlated with plexiform and RPE layers
      in histology. CONCLUSION: In vivo OCT imaging and quantification of guinea pig
      retina and optic nerve head parameters were repeatable and similar between eyes
      of the same animal. In vivo visibility of retinal cell layers correlated well
      with histological images. ABBREVIATIONS: optic nerve head (ONH), retinal ganglion
      cell (RGC), spectral domain optical coherence tomography (SD-OCT), enhanced depth
      imaging (EDI), minimum rim width (MRW), hematoxylin and eosin (H & E).

PMID- 29641940
TI  - PD-1/PD-L1 pathway inhibitors in advanced prostate cancer.
AB  - INTRODUCTION: Pharmacological inhibition of immune checkpoint receptors or their
      ligands represents a transformative breakthrough in the management of multiple
      cancers. However, immune checkpoint inhibitors have yet to be FDA-approved for
      the management of metastatic prostate cancer (PCa), the commonest non-cutaneous
      malignancy in men. Areas covered: We review our current understanding of the PD
      1/PD-L1 pathway in cancer, the use of anti-PD-1/PD-L1 therapeutics in PCa, and
      potential subgroups of PCa patients who may derive the greatest benefit from
      these agents (such as men with tumors that have expression of PD-L1 and/or high
      mutational load). We also review the prior and current clinical trials evaluating
      the blockade of PD-1/PD-L1 in PCa, highlighting some of the key ongoing studies
      of greatest relevance to the field. Expert commentary: Clinical trials
      investigating PD-1/PD-L1 inhibitors should be encouraged in patients with PCa.
      While it is unlikely that immune checkpoint monotherapies will produce long
      lasting responses in a substantial proportion of patients, there is early
      evidence of activity in some patient subsets. These subgroups may include those
      with high PD-L1 expression, those with hypermutated or microsatellite-unstable
      tumors, and those enriched for germline and/or somatic DNA-repair gene mutations
      (e.g. intraductal/ductal histology, primary Gleason pattern 5, and perhaps AR-V7
      positive tumors).

PMID- 29641941
TI  - Implementation and new insights in molecular diagnostics for HIV infection.
AB  - INTRODUCTION: Acquired immunodeficiency syndrome (AIDS) is a kind of acquired
      disease that breaks down the immune system. Human immunodeficiency virus (HIV) is
      the causative agent of AIDS. By the end of 2016, there were 36.7 million people
      living with HIV worldwide. Early diagnosis can alert infected individuals to risk
      behaviors in order to control HIV transmission. Infected individuals are also
      benefited from proper treatment and management upon early diagnosis. Thanks to
      the public awareness of the disease, the annual increase of new HIV infections
      has been slowly declining over the past decades. The advent of molecular
      diagnostics has allowed early detection and better management of HIV infected
      patients. Areas covered: In this review, the authors summarized and discussed the
      current and future technologies in molecular diagnosis as well as the biomarkers
      developed for HIV infection. Expert Commentary: A simple and rapid detection of
      viral load is important for patients and doctors to monitor HIV progression and
      antiretroviral treatment efficiency. In the near future, it is expected that new
      technologies such as digital PCR and CRISPR-based technology will play more
      important role in HIV detection and patient management.

PMID- 29641942
TI  - Trump and the GOP agenda: implications for retirement policy.
AB  - This commentary provides background on the current state of American retirement,
      highlights recent efforts to reform retirement policy, and predicts what to
      expect under President Donald Trump. Retirement has not been a major focus of
      national policy makers in recent years. Early actions during the Trump
      administration to undo Obama administration policies may make it more difficult
      for individuals to save for retirement. While it is impossible to predict the
      future with any certainty, long-standing trends and recent political developments
      suggest that major action will not be taken during the Trump presidency to boost
      retirement security.

PMID- 29641943
TI  - Alignment of an interprofessional student learning experience with a hospital
      quality improvement initiative.
AB  - Assessment of interprofessional education (IPE) frequently focuses on students'
      learning outcomes including changes in knowledge, skills, and/or attitudes. While
      a foundational education in the values and information of their chosen profession
      is critical, interprofessional learning follows a continuum from formal education
      to practice. The continuum increases in significance and complexity as learning
      becomes more relationship based and dependent upon the ability to navigate
      complex interactions with patients, families, communities, co-workers, and
      others. Integrating IPE into collaborative practice is critical to enhancing
      students' experiential learning, developing teamwork competencies, and
      understanding the complexity of teams. This article describes a project that
      linked students with a hospital-based quality-improvement effort to focus on the
      acquisition and practice of teamwork skills and to determine the impact of
      teamwork on patient and quality outcome measures. A hospital unit was identified
      with an opportunity for improvement related to quality care, patient
      satisfaction, employee engagement, and team behaviours. One hundred and thirty
      seven students from six health profession colleges at the Medical University of
      South Carolina underwent TeamSTEPPS(r) training and demonstrated proficiency of
      their teamwork-rating skills with the TeamSTEPPS(r) Team Performance Observation
      Tool (T-TPO). Students observed real-time team behaviours of unit staff before
      and after staff attended formal TeamSTEPPS(r) training. The students collected a
      total of 778 observations using the T-TPO. Teamwork performance on the unit
      improved significantly across all T-TPO domains (team structure, communication,
      leadership, situation monitoring, and mutual support). Significant improvement in
      each domain continued post-intervention and at 15-month follow-up, improvement
      remained significant compared to baseline. Student engagement in TeamSTEPPS(r)
      training and demonstration of their reliability as teamwork-observers was a
      valuable learning experience and also yielded an opportunity to gather unique,
      and otherwise difficult to attain, data from a hospital unit for use by quality
      managers and administrators.

PMID- 29641944
TI  - Implementation of Online Opioid Prevention, Recognition and Response Trainings
      for Laypeople: Year 1 Survey Results.
AB  - BACKGROUND: This article reports on the first implementation of an online opioid
      overdose prevention, recognition and response training for laypeople. The
      training was disseminated nationally in November 2014. Between 2000 and 2014,
      U.S. opioid deaths increased by 200%. The importance of complementary approaches
      to reduce opioid overdose deaths, such as online training, cannot be overstated.
      OBJECTIVES: A retrospective evaluation was conducted to assess perceived
      knowledge, skills to intervene in an overdose, confidence to intervene, and
      satisfaction with the training. MEASUREMENTS: Descriptive statistics were used to
      report sample characteristics, compare experiences with overdose and/or naloxone
      between subgroups, and describe participants' satisfaction with the trainings. Z
      ratios were used to compare independent proportions, and paired t-tests were used
      to compare participant responses to items pre- and posttraining, including
      perceived confidence to intervene and perceived knowledge and skills to intervene
      successfully. RESULTS: Between January and October 2015, 2,450 laypeople took the
      online training; 1,464 (59.8%) agreed to be contacted. Of these, 311 (21.2% of
      those contacted) completed the survey. Over 80% reported high satisfaction with
      content, format and mode of delivery and high satisfaction with items related to
      confidence and overdose reversal preparedness. Notably, 89.0% of participants
      felt they had the knowledge and skills to intervene successfully posttraining
      compared to 20.3% pretraining (z = -17.2, p <.001). Similarly, posttraining,
      87.8% of participants felt confident they could successfully intervene compared
      to 24.4% pretraining (z = -15.9, p <.001). CONCLUSIONS: This study demonstrates
      the effectiveness of the GetNaloxoneNow.org online training for laypeople.

PMID- 29641946
TI  - Preventing Today's Survivors of Breast Cancer From Becoming Tomorrow's Cardiac
      Patients.

PMID- 29641945
TI  - Investigating Italian parents' vaccine hesitancy: A cross-sectional survey.
AB  - This cross-sectional survey was designed to assess the prevalence of vaccine
      hesitancy and to identify factors associated among a randomly selected sample of
      parents. A questionnaire was self-administered from October to December 2017 to a
      sample of parents of children aged 2 to 6 years attending five randomly selected
      pre-schools in the geographic area of Naples, Italy. Out of the 727 selected
      parents, 437 returned the questionnaires for a response rate of 60.1%. The median
      of Parent Attitudes about Childhood Vaccines Survey (PACV) score among
      participants was 45.8 with a total of 141 parents (34.7%) scored a value >=50 and
      were defined hesitant about the childhood vaccinations. Vaccine hesitancy was
      significantly more common among those who were concerned and among those were not
      sure that any one of the childhood shots might not be safe, among those who were
      concerned that their children might have a serious side effect from a shot, among
      those who were concerned that a shot might not prevent the disease, among those
      who delayed and refused at least a shot of vaccine for their children, and in
      those who are not sure and uncertain in the pediatrician. More than half of
      parents (53.8%) expressed a desire to receive additional information about the
      childhood vaccinations. Parents who were not sure and uncertain that to follow
      the recommended shot schedule is a good idea for their children and those who
      were parents of first-born children were more likely to need additional
      information. This study finds a high prevalence of vaccine hesitancy among
      parents suggesting that in the immunization program is necessary to achieve a
      higher quality of the relationship between pediatricians and the community.

PMID- 29641948
TI  - That an Ounce of Prevention Is Worth a Pound of Cure Is Certainly True for
      Patients With Breast Cancer.

PMID- 29641947
TI  - Moving Away From a One-Size-Fits-All Approach to Gastric Cancer.

PMID- 29641949
TI  - Genetic Diversity and Treatment Implications in Gastric and Gastroesophageal
      Cancers: One Size Does Not Fit All.

PMID- 29641950
TI  - Gastric Cancer: Recent Molecular Classification Advances, Racial Disparity, and
      Management Implications.
AB  - Gastric adenocarcinoma remains an aggressive and poorly understood malignancy
      with a heterogeneous presentation and tumor biology. The current histologic and
      anatomic classification has been ineffective in guiding therapy, with only
      marginal improvement in outcome over time. Furthermore, the variation in
      presentation and disease among racial and ethnic groups amplifies the complexity
      of this cancer. An understanding of the clinical and molecular variability is
      important for effective treatment. Recent advances in molecular biology have
      better defined gastric cancer subtypes. We systematically review recent
      literature on the molecular classification of gastric adenocarcinoma and the
      associated management implications, with an emphasis on Hispanic and Native
      American populations.

PMID- 29641951
TI  - Priorities in the Cardiovascular Care of Breast Cancer Survivors.
AB  - Breast cancer is the most common malignancy in women with more than 3 million
      breast cancer survivors in the United States alone. Survivors of breast cancer
      suffer from an increased burden of cardiovascular risk factors and disease. The
      focus of this review is to describe the epidemiology of cardiovascular disease in
      breast cancer survivors, including the cardiovascular concerns observed with
      common cancer therapies. Strategies to improve upon the early detection and
      treatment of cardiovascular disease, including clinical prediction algorithms,
      biomarkers, and imaging measures are also reviewed, and the use of
      cardioprotective therapies to mitigate risk are summarized. Finally, the need for
      evidence-based research to inform and improve upon the multidisciplinary care of
      this growing population is highlighted.

PMID- 29641952
TI  - Lessons in Integrating Shared Decision-Making Into Cancer Care.
AB  - The benefits of shared decision-making (SDM) in health care delivery are well
      documented, but implementing SDM at the institutional level is challenging,
      particularly when patients have complex illnesses and care needs, as in cancer.
      Denmark's Lillebaelt Hospital, in creating The Patient's Cancer Hospital in
      Vejle, has learned key lessons in implementing SDM so that the organization's
      culture is actually being transformed. In short, SDM is becoming part of the
      fabric of care, not a mere add-on to it. Specifically, the hospital chose and
      structured its leadership to ensure that SDM is constantly championed. It
      organized multiple demonstration projects focused on use of decision aids,
      patient-reported outcome measures, and better communication tools and practices.
      It designed programs to train clinicians in the art of doctor-patient
      communication. It used research evidence to inform development of the decision
      aids that its clinicians use with their patients. And it rigorously measured SDM
      performance in an ongoing fashion so that progress could be tracked and refined
      to ensure continuous improvement. Initial data on the institution's SDM
      initiatives from the Danish national annual survey of patients' experiences show
      substantial progress, thereby motivating Lillebaelt to reassert its commitment to
      the effort, to share what it has learned, and to invite dialogue among all cancer
      care organizations as they seek to fully integrate SDM in daily clinical
      practice.

PMID- 29641953
TI  - Pilot Study of the Effects of Ambient Light Level Variation on Spectral Domain
      Anterior Segment OCT-Derived Angle Metrics in Caucasians versus Asians.
AB  - PURPOSE: To investigate the effects of ambient light level variation on spectral
      domain anterior segment optical coherence tomography (SD-OmicronCT)-derived
      anterior chamber angle metrics in Caucasians versus Asians. MATERIALS AND
      METHODS: Caucasian (n = 24) and Asian participants of Chinese ancestry (n = 24)
      with open angles on gonioscopy had one eye imaged twice at five strictly
      controlled, ambient light levels. Ethnicity was self-reported. Light levels were
      strictly controlled using a light meter at 1.0, 0.75, 0.5, 0.25, and 0 foot
      candle illumination levels. SD-OCT 5-line raster scans at the inferior 270
      degrees  irido-corneal angle were measured by two trained, masked graders from
      the Doheny Image Reading Center using customized Image-J software. Schwalbe's
      line-angle opening distance (SL-AOD) and SL-trabecular iris space area (SL-TISA)
      in different light meter readings (LMRs) between the two groups were compared.
      RESULTS: Baseline light SL-AOD and SL-TISA measured 0.464 +/- 0.115mm/0.351 +/-
      0.110mm2 and 0.344 +/- 0.118mm/0.257 +/- 0.092mm2, respectively, in the Caucasian
      and the Asian group. SL-AOD and SL-TISA in each LMR were significantly larger in
      the Caucasian group compared to the Asian group (p < 0.05). Despite this
      difference in angle size between the groups, there were no statistically
      significant differences in the degree of change in angle parameters from light to
      dark (% changes in SL-AOD or SL-TISA between the two groups were statistically
      similar with all p-values >0.3). CONCLUSION: SL-based angle dimensions using SD
      OCT are sensitive to changes in ambient illumination in participants with
      Caucasian and Asian ancestry. Although Caucasian eyes had larger baseline angle
      opening under bright light conditions, the light-to-dark change in angle
      dimensions was similar in the two groups.

PMID- 29641954
TI  - More on Low-Dose versus Standard-Dose Intravenous Alteplase in Acute Ischemic
      Stroke.

PMID- 29641955
TI  - The Blind Men and the Elephant - Aligning Efforts in Global Health.

PMID- 29641956
TI  - Finding a Treatment for ALS - Will Gene Editing Cut It?

PMID- 29641957
TI  - A New Left Ventricular Assist Device - Better, but Still Not Ideal.

PMID- 29641958
TI  - Embolization of Struts from an Inferior Vena Cava Filter.

PMID- 29641959
TI  - Probable Sexually Transmitted Zika Virus Infection in a Pregnant Woman.

PMID- 29641960
TI  - Pulmonary Metastases from Chondroblastic Osteosarcoma.

PMID- 29641961
TI  - Accessibility of Medical Diagnostic Equipment - Implications for People with
      Disability.

PMID- 29641962
TI  - Case 11-2018: A 48-Year-Old Woman with Recurrent Venous Thromboembolism and
      Pulmonary Artery Aneurysm.

PMID- 29641963
TI  - Breakthrough-Therapy Designation - An FDA Perspective.

PMID- 29641964
TI  - Zika Virus Shedding in Semen of Symptomatic Infected Men.
AB  - BACKGROUND: Zika virus (ZIKV) is an emerging mosquito-borne flavivirus that has
      been linked to adverse birth outcomes. Previous reports have shown that person-to
      person transmission can occur by means of sexual contact. METHODS: We conducted a
      prospective study involving men with symptomatic ZIKV infection to determine the
      frequency and duration of ZIKV shedding in semen and urine and to identify risk
      factors for prolonged shedding in these fluids. Specimens were obtained twice per
      month for 6 months after illness onset and were tested by real-time reverse
      transcriptase-polymerase-chain-reaction (RT-PCR) assay for ZIKV RNA and by Vero
      cell culture and plaque assay for infectious ZIKV. RESULTS: A total of 1327 semen
      samples from 184 men and 1038 urine samples from 183 men were obtained 14 to 304
      days after illness onset. ZIKV RNA was detected in the urine of 7 men (4%) and in
      the semen of 60 (33%), including in semen samples from 22 of 36 men (61%) who
      were tested within 30 days after illness onset. ZIKV RNA shedding in semen
      decreased substantially during the 3 months after illness onset but continued for
      281 days in 1 man (1%). Factors that were independently associated with prolonged
      RNA shedding included older age, less frequent ejaculation, and the presence of
      certain symptoms at the time of initial illness. Infectious ZIKV was isolated
      from 3 of 78 semen samples with detectable ZIKV RNA, all obtained within 30 days
      after illness onset and all with at least 7.0 log10 ZIKV RNA copies per
      milliliter of semen. CONCLUSIONS: ZIKV RNA was commonly present in the semen of
      men with symptomatic ZIKV infection and persisted in some men for more than 6
      months. In contrast, shedding of infectious ZIKV appeared to be much less common
      and was limited to the first few weeks after illness onset. (Funded by the
      Centers for Disease Control and Prevention.).

PMID- 29641965
TI  - Contralateral Cervical Nerve Transfer for Arm Paralysis.

PMID- 29641967
TI  - Virus in Semen and the Risk of Sexual Transmission.

PMID- 29641966
TI  - Genetics and Pathogenesis of Diffuse Large B-Cell Lymphoma.
AB  - BACKGROUND: Diffuse large B-cell lymphomas (DLBCLs) are phenotypically and
      genetically heterogeneous. Gene-expression profiling has identified subgroups of
      DLBCL (activated B-cell-like [ABC], germinal-center B-cell-like [GCB], and
      unclassified) according to cell of origin that are associated with a differential
      response to chemotherapy and targeted agents. We sought to extend these findings
      by identifying genetic subtypes of DLBCL based on shared genomic abnormalities
      and to uncover therapeutic vulnerabilities based on tumor genetics. METHODS: We
      studied 574 DLBCL biopsy samples using exome and transcriptome sequencing, array
      based DNA copy-number analysis, and targeted amplicon resequencing of 372 genes
      to identify genes with recurrent aberrations. We developed and implemented an
      algorithm to discover genetic subtypes based on the co-occurrence of genetic
      alterations. RESULTS: We identified four prominent genetic subtypes in DLBCL,
      termed MCD (based on the co-occurrence of MYD88L265P and CD79B mutations), BN2
      (based on BCL6 fusions and NOTCH2 mutations), N1 (based on NOTCH1 mutations), and
      EZB (based on EZH2 mutations and BCL2 translocations). Genetic aberrations in
      multiple genes distinguished each genetic subtype from other DLBCLs. These
      subtypes differed phenotypically, as judged by differences in gene-expression
      signatures and responses to immunochemotherapy, with favorable survival in the
      BN2 and EZB subtypes and inferior outcomes in the MCD and N1 subtypes. Analysis
      of genetic pathways suggested that MCD and BN2 DLBCLs rely on "chronic active" B
      cell receptor signaling that is amenable to therapeutic inhibition. CONCLUSIONS:
      We uncovered genetic subtypes of DLBCL with distinct genotypic, epigenetic, and
      clinical characteristics, providing a potential nosology for precision-medicine
      strategies in DLBCL. (Funded by the Intramural Research Program of the National
      Institutes of Health and others.).

PMID- 29641968
TI  - Cardiac Arrest during Competitive Sports.

PMID- 29641969
TI  - Diagnostic Use of Base Excess in Acid-Base Disorders.

PMID- 29641970
TI  - The FDA Breakthrough-Drug Designation - Four Years of Experience.

PMID- 29641971
TI  - Prognostic values of common clinical parameters in advanced pancreatic ductal
      adenocarcinoma: a large multicenter cohort study of ten years.
AB  - OBJECTIVE: We conducted a multicenter cohort study to investigate the prognostic
      value of some commonly-used laboratory indices in advanced pancreatic ductal
      adenocarcinoma (PDAC). METHODS: A multicenter cohort study was conducted from
      2004 to 2013. The associations between laboratory indices and prognosis of
      advanced PDAC were examined. RESULTS: This cohort consisted of 553 females
      (36.2%) and 973 males (63.8%). Patients at cancer stage III and IV were 595
      (39.0%) and 931 (61.0%), respectively. The median survival of stage III patients
      was 9.0 months, with 3-, 6-, and 12-month survival rates of 94.5%, 73.4%, and
      28.5%, respectively. The median survival of stage IV patients was 5.4 months,
      with 3-, 6-, and 12-month survival rates of 79.3%, 42.9%, and 15.0%,
      respectively. In multivariate analyses, primary tumor diameter, low albumin, and
      elevated CA19-9 were associated with decreased survival for stage III patients.
      Age, smoking, primary tumor diameter, elevated ALT or AST, low albumin, and
      elevated CA19-9 were associated with decreased survival for stage IV patients.
      CONCLUSION: Elevated CA19-9 level, decreased albumin level, and tumor size were
      associated with worse survival in stage III patients. Meanwhile, advanced age,
      smoking, and ALT or AST level were negatively correlated to prognosis in stage IV
      patients.

PMID- 29641972
TI  - Subtypes of MDSCs in mechanisms and prognosis of gastric cancer and are inhibited
      by epirubicin and paclitaxel.
AB  - Myeloid-derived suppressor cells (MDSCs) are thought to play a critical
      immunosuppressive role in tumorigenesis. In this project, we aimed to investigate
      subset alteration of MDSCs in gastric cancer (GC), and the effects of epirubicin
      (EPI) and paclitaxel (TAX) on MDSCs. The frequencies of MDSC subsets in
      peripheral blood were observed by using flow cytometry after treatment with EPI-
      or TAX- based chemotherapy in GC patients. After treatment with EPI or TAX in
      vitro, the subsets, apoptosis, cell cycle, and MAPK and NF-kappaB protein
      expressions of mouse bone marrow MDSCs were analyzed. The frequency of MDSCs in
      the peripheral blood of GC patients was higher than that in healthy controls.
      Granulocyte-type MDSCs (G-MDSCs) were significantly more than monocyte-type MDSCs
      (M-MDSCs) in GC patients. The frequencies of MDSC subsets in the peripheral blood
      decreased after EPI- or TAX-based chemotherapy. High levels of MDSC subsets were
      correlated with low cancer differentiation degree. High level of M-MDSCs was
      related to lymph node metastasis, and was negatively correlated with the overall
      survival of GC patients. After treatment with EPI or TAX, levels of mouse bone
      marrow MDSC subsets decreased significantly in vitro. Arg-1 secretion and
      expression of total and phosphorylated MAPK and NF-kappaB by MDSCs decreased. EPI
      or TAX decreases the levels of MDSCs, inhibits the proliferation and function of
      MDSCs in vitro, and induces their apoptosis via the MAPK and NF-kappaB signaling
      pathways.

PMID- 29641973
TI  - What can we do to optimize stem and progenitor cell therapy for heart failure?
AB  - Stem cells are a promising solution for the treatment of heart failure due to
      their ability to repopulate injured myocardium and restore cardiac function.
      However, many hindrances (such as low survival/viability and integration of
      transplanted cells, poor homing and cardiac differentiation efficiency, and
      inadequate cell retention and engraftment) compromise the full regenerative
      potential provided by stem cells. Therefore, it is necessary to optimize stem
      cell/progenitor therapy to improve clinical efficacy. By analogy, in order for
      crops to grow, good seeds are needed. They also need sufficient fertilizer,
      herbicides, and pesticides to be "optimized." In this review, we provide a
      comprehensive overview of "seeds" (comparison of stem cell types, different
      combinations of stem cells, age, size, and dose of stem cells) and "fertilizers"
      (optimizing stem/progenitor cells and genetic strategies, preconditioning with
      drugs, and physical changes) for heart failure.

PMID- 29641974
TI  - A precision medicine approach in sarcoma: identification of patients who may
      benefit from early use of pazopanib.
AB  - Soft tissue sarcomas (STS) are a heterogeneous group of over 100 histologically
      and genetically distinct mesenchymal tumors. Standard of care for metastatic STS
      has historically relied on anthracycline-based chemotherapy regimens. Although
      effective for some patients, conventional chemotherapeutic agents used in STS are
      associated with substantial toxicity and also are not equally effective in all
      histologic subtypes of sarcoma. Pazopanib is an orally active antiangiogenic drug
      that is approved for non-adipogenic sarcomas after failure of at least one line
      of previous chemotherapy, and has a relatively favorable toxicity profile.
      Earlier use of pazopanib may be a better choice for patients with subtypes of
      sarcoma that do not respond well to conventional chemotherapy or those who are
      unlikely to tolerate chemotherapy. Here we review the evidence for the activity
      and toxicity profile of pazopanib and consider potential histologic, clinical,
      and genetic predictive factors that can help to guide treatment choices. Further
      prospective studies validating these observations may lead to refinement of a
      precision medicine approach to match ideal sarcoma patients to earlier treatment
      with pazopanib over traditional chemotherapy.

PMID- 29641975
TI  - Prediction of lysine glutarylation sites by maximum relevance minimum redundancy
      feature selection.
AB  - Lysine glutarylation is new type of protein acylation modification in both
      prokaryotes and eukaryotes. To better understand the molecular mechanism of
      glutarylation, it is important to identify glutarylated substrates and their
      corresponding glutarylation sites accurately. In this study, a novel
      bioinformatics tool named GlutPred is developed to predict glutarylation sites by
      using multiple feature extraction and maximum relevance minimum redundancy
      feature selection. On the one hand, amino acid factors, binary encoding, and the
      composition of k-spaced amino acid pairs features are incorporated to encode
      glutarylation sites. And the maximum relevance minimum redundancy method and the
      incremental feature selection algorithm are adopted to remove the redundant
      features. On the other hand, a biased support vector machine algorithm is used to
      handle the imbalanced problem in glutarylation sites training dataset. As
      illustrated by 10-fold cross-validation, the performance of GlutPred achieves a
      satisfactory performance with a Sensitivity of 64.80%, a Specificity of 76.60%,
      an Accuracy of 74.90% and a Matthew's correlation coefficient of 0.3194. Feature
      analysis shows that some k-spaced amino acid pair features play the most
      important roles in the prediction of glutarylation sites. The conclusions derived
      from this study might provide some clues for understanding the molecular
      mechanisms of glutarylation.

PMID- 29641976
TI  - MET amplification, expression, and exon 14 mutations in colorectal
      adenocarcinoma.
AB  - MET amplification, expression, and splice mutations at exon 14 result in
      dysregulation of the MET signaling pathway. The aim of this study was to identify
      the relationship between MET amplification, protein or mRNA expression, and
      mutations in colorectal cancer (CRC). MET immunohistochemistry was used for MET
      protein expression analysis, and fluorescence in situ hybridization was used for
      MET amplification detection. Both analyses were performed in tissue microarrays
      containing 294 colorectal adenocarcinoma tissue samples and 131 samples of
      adjacent normal epithelial tissue. MET mRNA expression was examined by real-time
      quantitative polymerase chain reaction in 72 fresh colorectal adenocarcinoma
      tissue samples and adjacent normal colon tissue. Polymerase chain reaction
      sequencing was performed to screen for MET exon 14 splice mutations in 59 fresh
      CRC tissue samples. Our results showed that MET protein expression was higher in
      colorectal tumor tissue than in adjacent normal intestinal epithelium. Positive
      MET protein expression was associated with significantly poorer overall survival
      and disease-free survival. Multivariate analysis revealed that positive MET
      protein expression was an independent risk factor for disease-free survival but
      not for overall survival. MET mRNA expression was upregulated in tumor tissues
      compared with the adjacent normal tissues. The incidence of MET amplification was
      4.4%. None of the patients was positive for MET mutation. Collectively, MET was
      overexpressed in colorectal adenocarcinoma, and its positive protein expression
      predicted a poorer outcome in CRC patients. Furthermore, according to our
      results, MET amplification and exon 14 mutation are extremely rare events in
      colorectal adenocarcinoma.

PMID- 29641977
TI  - Chronic low-dose exposure of nonylphenol alters energy homeostasis in the
      reproductive system of female rats.
AB  - Nonylphenol (NP) as a confirmed endocrine disrupt chemical that causes
      reproductive and developmental toxicity. Previous studies focused only on short
      term, high-dose exposure in vivo, or in vitro on female reproductive toxicity,
      which cannot accurately simulate the real human exposure scenario. The present
      study aims to explore NP toxicity and the underlying mechanisms of chronic low
      dose NP exposure (500 MUg/kg.bw/day, for 8 weeks) in the reproductive system of
      female rats. The results indicated that NP exposure caused female reproductive
      toxicity, including alterations in serum 17beta-estradiol (E2) levels, endometria
      hyperplasia, altered oogenesis and significant changes in the metabolic profile
      observed in urine, serum, uterus and ovary. Furthermore, expression of the energy
      sensitive proteins carnitine palmitoyltransferase I (CPTI), adenosine 5'
      monophosphate-activated protein kinase (AMPK) and peroxisome proliferator
      activated receptor gamma (PPAR-gamma) were found to be down-regulated in uterus
      under NP exposure, which suggested the impaired fatty acid oxidation.
      Accordingly, a comprehensive metabolomics study in key reproductive tissues and
      body fluids revealed that 12 metabolites were associated with energy metabolism
      as potential biomarkers for the evaluation of low toxicity at early stages, with
      L-carnitines being the most representative ones. The present findings provide
      evidence that chronic low-dose NP exposure can significantly disrupt energy
      homeostasis in females, thus offering further insights into NP reproductive
      toxicity.

PMID- 29641978
TI  - Estrogen-related receptor alpha is involved in Alzheimer's disease-like
      pathology.
AB  - Estrogen-related receptor alpha (ERRalpha) is a transcriptional factor associated
      with mitochondrial biogenesis and energy metabolism. However, little is known
      about the role of ERRalpha in Alzheimer's disease (AD). Here, we report that in
      APP/PS1 mice, an animal model of AD, ERRalpha protein and mRNA were decreased in
      a region- and age-dependent manner. In HEK293 cells that stably express human
      full-length beta-amyloid precursor protein (APP), overexpression of ERRalpha
      inhibited the amyloidogenic processing of APP and consequently reduced Abeta1
      40/1-42 level. ERRalpha overexpression also attenuated Tau phosphorylation at
      selective sites, with the concomitant reduction of glycogen synthase kinase 3beta
      (GSK3beta) activity. Interestingly, alterations of APP processing and Tau
      phosphorylation induced by hydrogen peroxide were reversed by ERRalpha
      overexpression in HEK/APP cells. These results indicated that ERRalpha plays a
      functional role in AD pathology. By attenuating both amyloidogenesis and Tau
      phosphorylation, ERRalpha may serve as a potential therapeutic target for AD.

PMID- 29641979
TI  - Nanoparticles modulate membrane interactions of human Islet amyloid polypeptide
      (hIAPP).
AB  - The dramatic expansion of nanotechnology applications, particularly the advent of
      nanomaterials and nanoparticles (NPs) into the consumer economy, have led to
      heightened awareness of their potential health risks. This study examines the
      impact of several NPs upon membrane-induced aggregation and bilayer interactions
      of the human Islet amyloid polypeptide (hIAPP). We report that several NPs -
      polymeric NPs, TiO2 NPs, and Au NPs displaying coating layers exhibiting
      different electrostatic charges - did not significantly interfere with the
      fibrillation process and fibril morphology of hIAPP, both in buffer or in
      biomimetic DMPC:DMPG vesicle solutions. Spectroscopic and microscopic analyses
      suggest, in fact, that the NPs promoted membrane-induced fibrillation.
      Importantly, we find that all the NPs examined, regardless of composition or
      surface properties, gave rise to more pronounced, synergistic bilayer
      interactions when co-incubated with hIAPP. NP-enhanced bilayer interactions of
      hIAPP might point to possible toxicity and pathogenicity risks of amyloidogenic
      peptides in the presence of NPs.

PMID- 29641980
TI  - Gene-culture coevolution under selection.
AB  - The joint evolutionary dynamics of phenotypes and genotypes are usually couched
      in terms of genetic variance contributions to changes in the phenotypic mean.
      Here, we study the evolution of a dichotomous phenotype whose transmission is
      controlled by one multi-allelic locus. The phenotype is under selection, which
      may be genotype-dependent. We answer classical population genetic questions about
      the phenogenotypic evolution, including the conditions for phenotypic and
      genotypic polymorphism, in terms of selection coefficients and rates of
      phenotypic transmission.

PMID- 29641981
TI  - Biodistribution and PET imaging of 89-zirconium labeled cerium oxide
      nanoparticles synthesized with several surface coatings.
AB  - Cerium oxide nanoparticles (CONPs) have unique surface chemistry allowing
      catalyst-like antioxidant properties, and are being investigated for several
      disease indications in medicine. Studies have utilized surface modified CONPs
      toward this application, but have been lacking in comprehensive biodistribution
      and pharmacokinetic data and a direct comparison to uncoated CONPs. We developed
      an enhanced single-pot synthesis of several coated CONPs and an efficient
      intrinsic core labeling of CONPs with the clinical PET isotope, zirconium-89,
      allowing detailed PET imaging and ex vivo biodistribution. All coated [89Zr]
      CONPs showed benefit in terms of biodistribution compared to uncoated [89Zr]
      CONPs, while retaining the intrinsic antioxidant properties. Among these,
      poly(acrylic acid) coated CONPs demonstrated excellent candidacy for clinical
      implementation due to their enhanced renal clearance and low reticuloendothelial
      system uptake. This work also demonstrates the value of intrinsic core labeling
      and PET imaging for evaluation of nanoparticle constructs to better inform future
      studies towards clinical use.

PMID- 29641983
TI  - Lipid nanocarriers loaded with natural compounds: Potential new therapies for age
      related neurodegenerative diseases?
AB  - Age related neurodegenerative disorders (ARND) are presented as the most
      debilitating and challenging diseases associated with the central nervous system.
      Despite the advent of active molecules with a positive role on neurodegenerative
      mechanisms, many of the current therapeutic strategies remain ineffective in
      treating or preventing ARND. Lipid nanocarriers have emerged as efficient
      delivery systems with the capability to cross biological barriers, especially the
      blood brain barrier (BBB). Also, when associated to natural compounds, lipid
      nanocarriers have demonstrated to be an interesting alternative to ARND therapies
      with multiple beneficial effects. This comprehensive review focus on state-of-the
      art lipid based nanocarriers for the delivery of natural compounds targeting
      neurodegeneration. A critical analysis of published reports will be also provided
      giving indications to researchers about the most promising ARND nanotherapy
      strategies.

PMID- 29641982
TI  - Concomitant Delivery of Paclitaxel and NuBCP-9 peptide for synergistic
      enhancement of cancer therapy.
AB  - Paclitaxel (PTX) is a microtubule inhibitor administered as an albumin-bound
      nanoformulation for the treatment of breast cancer. However, the effectiveness of
      PTX is limited by resistance mechanisms mediated in part by upregulation of the
      anti-apoptotic BCL-2 and P-glycoprotein (P-gp). Present investigation was
      designed to study the synergistic potential of NuBCP-9 and PTX loaded polymeric
      nanoparticles to minimize the dose and improve the efficacy and safety. PTX and
      NuBCP-9 loaded polylactic acid-polyethylene glycol-polypropylene glycol
      polyethylene glycol [PLA-(PEG-PPG-PEG)] nanoparticles were prepared by double
      emulsion solvent evaporation method. PTX and NuBCP-9 loaded NPs displayed an
      average size of 90 nm with spherical morphology. PTX and NuBCP-9 dual loaded NPs
      reducedIC50 by ~40-fold and acted synergistically. Treatment of the syngeneic EAT
      mice with PTX-NuBCP-9/NPs resulted in improved efficacy than that alone treated
      mice. Overall, the concomitant delivery PTX and NuBCP-9 loaded NPs showed
      superior activity than that of PTX and NuBCP-9 alone treated mice.

PMID- 29641984
TI  - Occurrence of Salmonella genomic island 1 (SGI1) in two African Proteus mirabilis
      strains isolated from diseased chicken flocks.
AB  - Two P. mirabilis strains, PmSHR21 and PmSHR38, were collected from chicken flocks
      in Sharkia Governorate, Egypt in 2016. The two strains showed multidrug
      resistance (MDR) phenotypes and were detected to harbour I) floR and sul1 genes
      conferring resistance to florfenicol and chloramphenicol, and sulfonamides,
      respectively, II) a ~1.9 kbp class 1 integron containing aadA2-lnuF genes
      conferring resistance to spectinomycin and streptomycin, and lincosamides,
      respectively. Interestingly, the two strains were detected to contain SGI1
      variant, SGI1-W and inserted between the 3' end of the chromosomal trmE gene and
      the hipB/hipA toxin/antitoxin homologue. Fingerprinting by ERIC-PCR of the two
      poultry strains identified in this study and the two human SGI1-carrying P.
      mirabilis strains described recently in our study showed identical ERIC-pattern
      between SGI1-W-carrying poultry and human strains, suggesting that they might be
      clonally related. The detection of SGI1 and its variants in P. mirabilis isolated
      from humans and chicken flocks in Egypt clarify the geographical and biological
      spreading through an inter-transmission pathway. To the best of our knowledge,
      this is the first study detecting SGI1-positive P. mirabilis isolated from
      chicken flocks in Africa.

PMID- 29641985
TI  - LC-MS guided isolation of diterpenoids from Sapium insigne with alpha-glucosidase
      inhibitory activities.
AB  - Ten new (1-10) and ten known (11-20) diterpenoids involving ent-atisane, ent-seco
      atisane, ent-kaurane and ent-seco-kaurane types were isolated from Sapium insigne
      under the guidance of LCMS-IT-TOF analyses. Their structures were characterized
      by extensive spectroscopic analyses (HRESIMS, UV, IR, 1D and 2D NMR). A putative
      biosynthetic pathway was proposed for ent-seco-atisane diterpenoids. Their
      inhibitory activities on alpha-glucosidase in vitro were tested for the first
      time. Compound 4 showed moderate inhibitory effect on alpha-glucosidase with an
      IC50 value of 0.34 mM via a noncompetitive inhibition mechanism (Ki = 0.27 mM).
      The preliminary structure-activity relationships of the ent-atisane diterpenoids
      inhibiting alpha-glucosidase were discussed.

PMID- 29641986
TI  - New chromane and chromene meroterpenoids from flowers of Rhododendron rubiginosum
      Franch. var. rubiginosum.
AB  - Six new chromane and chromene meroterpenoids rubiginosins A-F (1-2, and 4-7),
      together with three known ones, rubiginosin G (3) and anthopogochromenes A and B
      (8-9),were isolated from the flowers of Rhododendron rubiginosum Franch. var.
      rubiginosum. Among them, 1-4 were the chromane ones derived from an
      intramolecular [2 + 2] cycloaddition of their respective chromene precursors,
      making a 6/6/6/4- or 6/6/5/4-ring fused scaffold. The absolute configuration of
      the chiral center at C-2 of 1-9 was determined as S by chromane/chromene helicity
      rule and X-ray crystallograph. Notably, more attention should be paid to 6
      carboxyl derivatives, since the 6-carboxyl derivatives showed an abnormal
      diagnostic Cotton effect (CE) with respect to their normal diagnostic CE.
      Compounds 1-9 were tested for cytotoxicity against four cell lines (A549, HCT116,
      SK-HEP-1, and HL-60), and only 1, 3, 5, and 9 showed moderate cytotoxicity, while
      others were inactive, discovering the 6-carboxyl is crucial for their low
      cytotoxicity.

PMID- 29641987
TI  - Release of targeted protein nanoparticles from functional bacterial amyloids: A
      death star-like approach.
AB  - Sustained release of drug delivery systems (DDS) has the capacity to increase
      cancer treatment efficiency in terms of drug dosage reduction and subsequent
      decrease of deleterious side effects. In this regard, many biomaterials are being
      investigated but none offers morphometric and functional plasticity and
      versatility comparable to protein-based nanoparticles (pNPs). Here we describe a
      new DDS by which pNPs are fabricated as bacterial inclusion bodies (IB), that can
      be easily isolated, subcutaneously injected and used as reservoirs for the
      sustained release of targeted pNPs. Our approach combines the high performance of
      pNP, regarding specific cell targeting and biodistribution with the IB
      supramolecular organization, stability and cost effectiveness. This renders a
      platform able to provide a sustained source of CXCR4-targeted pNPs that
      selectively accumulate in tumor cells in a CXCR4+ colorectal cancer xenograft
      model. In addition, the proposed system could be potentially adapted to any other
      protein construct offering a plethora of possible new therapeutic applications in
      nanomedicine.

PMID- 29641988
TI  - Should rheumatoid factor (RF) (and antinuclear antibodies (ANA)) become routinary
      screening test for morbidities in the general population?: From the concept of
      "benign autoimmunity "to the concept of" autoimmunity as a red flag in preventive
      medicine"?

PMID- 29641989
TI  - Arginine Methylation Regulates MEIS2 Nuclear Localization to Promote Neuronal
      Differentiation of Adult SVZ Progenitors.
AB  - Adult neurogenesis is regulated by stem cell niche-derived extrinsic factors and
      cell-intrinsic regulators, yet the mechanisms by which niche signals impinge on
      the activity of intrinsic neurogenic transcription factors remain poorly defined.
      Here, we report that MEIS2, an essential regulator of adult SVZ neurogenesis, is
      subject to posttranslational regulation in the SVZ olfactory bulb neurogenic
      system. Nuclear accumulation of MEIS2 in adult SVZ-derived progenitor cells
      follows downregulation of EGFR signaling and is modulated by methylation of MEIS2
      on a conserved arginine, which lies in close proximity to nested binding sites
      for the nuclear export receptor CRM1 and the MEIS dimerization partner PBX1.
      Methylation impairs interaction with CRM1 without affecting PBX1 dimerization and
      thereby allows MEIS2 nuclear accumulation, a prerequisite for neuronal
      differentiation. Our results describe a form of posttranscriptional modulation of
      adult SVZ neurogenesis whereby an extrinsic signal fine-tunes neurogenesis
      through posttranslational modification of a transcriptional regulator of cell
      fate.

PMID- 29641990
TI  - HDAC1 and HDAC2 Modulate TGF-beta Signaling during Endothelial-to-Hematopoietic
      Transition.
AB  - The first hematopoietic stem and progenitor cells are generated during
      development from hemogenic endothelium (HE) through trans-differentiation. The
      molecular mechanisms underlying this endothelial-to-hematopoietic transition
      (EHT) remain poorly understood. Here, we explored the role of the epigenetic
      regulators HDAC1 and HDAC2 in the emergence of these first blood cells in vitro
      and in vivo. Loss of either of these epigenetic silencers through conditional
      genetic deletion reduced hematopoietic transition from HE, while combined
      deletion was incompatible with blood generation. We investigated the molecular
      basis of HDAC1 and HDAC2 requirement and identified TGF-beta signaling as one of
      the pathways controlled by HDAC1 and HDAC2. Accordingly, we experimentally
      demonstrated that activation of this pathway in HE cells reinforces hematopoietic
      development. Altogether, our results establish that HDAC1 and HDAC2 modulate TGF
      beta signaling and suggest that stimulation of this pathway in HE cells would be
      beneficial for production of hematopoietic cells for regenerative therapies.

PMID- 29641991
TI  - PLAG1 and USF2 Co-regulate Expression of Musashi-2 in Human Hematopoietic Stem
      and Progenitor Cells.
AB  - MSI2, which is expressed predominantly in hematopoietic stem and progenitor cells
      (HSPCs), enforces HSPC expansion when overexpressed and is upregulated in myeloid
      leukemias, indicating its regulated transcription is critical to balanced self
      renewal and leukemia restraint. Despite this, little is understood of the factors
      that enforce appropriate physiological levels of MSI2 in the blood system. Here,
      we define a promoter region that reports on endogenous expression of MSI2 and
      identify USF2 and PLAG1 as transcription factors whose promoter binding drives
      reporter activity. We show that these factors co-regulate, and are required for,
      efficient transactivation of endogenous MSI2. Coincident overexpression of USF2
      and PLAG1 in primitive cord blood cells enhanced MSI2 transcription and yielded
      cellular phenotypes, including expansion of CD34+ cells in vitro, consistent with
      that achieved by direct MSI2 overexpression. Global chromatin immunoprecipitation
      sequencing analyses confirm a preferential co-binding of PLAG1 and USF2 at the
      promoter of MSI2, as well as regulatory regions corresponding to genes with roles
      in HSPC homeostasis. PLAG1 and USF2 cooperation is thus an important contributor
      to stem cell-specific expression of MSI2 and HSPC-specific transcriptional
      circuitry.

PMID- 29641992
TI  - PITX2 Enhances the Regenerative Potential of Dystrophic Skeletal Muscle Stem
      Cells.
AB  - Duchenne muscular dystrophy (DMD), one of the most lethal genetic disorders,
      involves progressive muscle degeneration resulting from the absence of
      DYSTROPHIN. Lack of DYSTROPHIN expression in DMD has critical consequences in
      muscle satellite stem cells including a reduced capacity to generate myogenic
      precursors. Here, we demonstrate that the c-isoform of PITX2 transcription factor
      modifies the myogenic potential of dystrophic-deficient satellite cells. We
      further show that PITX2c enhances the regenerative capability of mouse DYSTROPHIN
      deficient satellite cells by increasing cell proliferation and the number of
      myogenic committed cells, but importantly also increasing dystrophin-positive
      (revertant) myofibers by regulating miR-31. These PITX2-mediated effects finally
      lead to improved muscle function in dystrophic (DMD/mdx) mice. Our studies reveal
      a critical role for PITX2 in skeletal muscle repair and may help to develop
      therapeutic strategies for muscular disorders.

PMID- 29641993
TI  - Pre-clinical validation of a next generation sequencing testing panel.
AB  - OBJECTIVE: Next Generation Sequencing (NGS) has become a useful tool for gene
      mutation testing which is required for targeted therapies. The aim of this study
      was to validate the GeneRead QIAact Actionable Insights Tumor Panel (Qiagen) on
      the GeneReader System in a diagnostic laboratory setting. METHODS: The GeneRead
      QIAact Actionable Insights Tumor Panel allows the analysis of 773 variant
      positions in 12 genes (ALK, BRAF, EGFR, ERBB2, ERBB3, ESR1, KIT, KRAS, NRAS,
      PDGFRA, PIK3CA and RAF1). For the validation of the panel we used a commercial
      available multiplex reference standard carrying 11 mutations in defined
      positions, samples from interlaboratory tests, and FFPE tumor samples from
      patients which were tested previously for mutations in KRAS, NRAS, BRAF, EGFR,
      KIT, and/or PDGFRA with pyrosequencing. RESULTS: Among the 122 tested samples,
      121 samples (99.2%) were successfully sequenced. The sensitivity and specificity
      for detecting variants was 100% and results proved to be reproducible and
      precise. 119 (98.3%) results were concordant to the expected results. The
      differences between NGS and pyrosequencing observed in two samples were due to a
      wrong analysis by the pyrosequencing software which did not cover the present
      mutations. CONCLUSION: Overall, the GeneRead QIAact Actionable Insights Tumor
      Panel was specific and sensitive for mutation analysis for targeted therapies and
      can be incorporated into laboratory diagnostics' daily practice.

PMID- 29641995
TI  - Meg3 Non-coding RNA Expression Controls Imprinting by Preventing Transcriptional
      Upregulation in cis.
AB  - Although many long non-coding RNAs (lncRNAs) are imprinted, their roles often
      remain unknown. The Dlk1-Dio3 domain expresses the lncRNA Meg3 and multiple
      microRNAs and small nucleolar RNAs (snoRNAs) on the maternal chromosome and
      constitutes an epigenetic model for development. The domain's Dlk1 (Delta-like-1)
      gene encodes a ligand that inhibits Notch1 signaling and regulates diverse
      developmental processes. Using a hybrid embryonic stem cell (ESC) system, we find
      that Dlk1 becomes imprinted during neural differentiation and that this involves
      transcriptional upregulation on the paternal chromosome. The maternal Dlk1 gene
      remains poised. Its protection against activation is controlled in cis by Meg3
      expression and also requires the H3-Lys-27 methyltransferase Ezh2. Maternal Meg3
      expression additionally protects against de novo DNA methylation at its promoter.
      We find that Meg3 lncRNA is partially retained in cis and overlaps the maternal
      Dlk1 in embryonic cells. Combined, our data evoke an imprinting model in which
      allelic lncRNA expression prevents gene activation in cis.

PMID- 29641994
TI  - A Common Allele in FGF21 Associated with Sugar Intake Is Associated with Body
      Shape, Lower Total Body-Fat Percentage, and Higher Blood Pressure.
AB  - Fibroblast growth factor 21 (FGF21) is a hormone that has insulin-sensitizing
      properties. Some trials of FGF21 analogs show weight loss and lipid-lowering
      effects. Recent studies have shown that a common allele in the FGF21 gene alters
      the balance of macronutrients consumed, but there was little evidence of an
      effect on metabolic traits. We studied a common FGF21 allele (A:rs838133) in
      451,099 people from the UK Biobank study, aiming to use the human allele to
      inform potential adverse and beneficial effects of targeting FGF21. We replicated
      the association between the A allele and higher percentage carbohydrate intake.
      We then showed that this allele is more strongly associated with higher blood
      pressure and waist-hip ratio, despite an association with lower total body-fat
      percentage, than it is with BMI or type 2 diabetes. These human phenotypes of
      variation in the FGF21 gene will inform research into FGF21's mechanisms and
      therapeutic potential.

PMID- 29641996
TI  - Transcriptional Dysregulation of MYC Reveals Common Enhancer-Docking Mechanism.
AB  - Transcriptional dysregulation of the MYC oncogene is among the most frequent
      events in aggressive tumor cells, and this is generally accomplished by
      acquisition of a super-enhancer somewhere within the 2.8 Mb TAD where MYC
      resides. We find that these diverse cancer-specific super-enhancers, differing in
      size and location, interact with the MYC gene through a common and conserved CTCF
      binding site located 2 kb upstream of the MYC promoter. Genetic perturbation of
      this enhancer-docking site in tumor cells reduces CTCF binding, super-enhancer
      interaction, MYC gene expression, and cell proliferation. CTCF binding is highly
      sensitive to DNA methylation, and this enhancer-docking site, which is
      hypomethylated in diverse cancers, can be inactivated through epigenetic editing
      with dCas9-DNMT. Similar enhancer-docking sites occur at other genes, including
      genes with prominent roles in multiple cancers, suggesting a mechanism by which
      tumor cell oncogenes can generally hijack enhancers. These results provide
      insights into mechanisms that allow a single target gene to be regulated by
      diverse enhancer elements in different cell types.

PMID- 29641997
TI  - MYC Releases Early Reprogrammed Human Cells from Proliferation Pause via
      Retinoblastoma Protein Inhibition.
AB  - Here, we report that MYC rescues early human cells undergoing reprogramming from
      a proliferation pause induced by OCT3/4, SOX2, and KLF4 (OSK). We identified ESRG
      as a marker of early reprogramming cells that is expressed as early as day 3
      after OSK induction. On day 4, ESRG positive (+) cells converted to a TRA-1-60
      (+) intermediate state. These early ESRG (+) or TRA-1-60 (+) cells showed a
      proliferation pause due to increased p16INK4A and p21 and decreased endogenous
      MYC caused by OSK. Exogenous MYC did not enhance the appearance of initial
      reprogramming cells but instead reactivated their proliferation and improved
      reprogramming efficiency. MYC increased expression of LIN41, which potently
      suppressed p21 post-transcriptionally. MYC suppressed p16 INK4A. These changes
      inactivated retinoblastoma protein (RB) and reactivated proliferation. The RB
      regulated proliferation pause does not occur in immortalized fibroblasts, leading
      to high reprogramming efficiency even without exogenous MYC.

PMID- 29641998
TI  - Condition-Specific Modeling of Biophysical Parameters Advances Inference of
      Regulatory Networks.
AB  - Large-scale inference of eukaryotic transcription-regulatory networks remains
      challenging. One underlying reason is that existing algorithms typically ignore
      crucial regulatory mechanisms, such as RNA degradation and post-transcriptional
      processing. Here, we describe InfereCLaDR, which incorporates such elements and
      advances prediction in Saccharomyces cerevisiae. First, InfereCLaDR employs a
      high-quality Gold Standard dataset that we use separately as prior information
      and for model validation. Second, InfereCLaDR explicitly models transcription
      factor activity and RNA half-lives. Third, it introduces expression subspaces to
      derive condition-responsive regulatory networks for every gene. InfereCLaDR's
      final network is validated by known data and trends and results in multiple
      insights. For example, it predicts long half-lives for transcripts of the nucleic
      acid metabolism genes and members of the cytosolic chaperonin complex as targets
      of the proteasome regulator Rpn4p. InfereCLaDR demonstrates that more
      biophysically realistic modeling of regulatory networks advances prediction
      accuracy both in eukaryotes and prokaryotes.

PMID- 29641999
TI  - JMJD1B Demethylates H4R3me2s and H3K9me2 to Facilitate Gene Expression for
      Development of Hematopoietic Stem and Progenitor Cells.
AB  - The arginine methylation status of histones dynamically changes during many
      cellular processes, including hematopoietic stem/progenitor cell (HSPC)
      development. The arginine methyltransferases and the readers that transduce the
      histone codes have been defined. However, whether arginine demethylation actively
      occurs in cells and what enzyme demethylates the methylarginine residues during
      various cellular processes are unknown. We report that JMJD1B, previously
      identified as a lysine demethylase for H3K9me2, mediates arginine demethylation
      of H4R3me2s and its intermediate, H4R3me1. We show that demethylation of H4R3me2s
      and H3K9me2s in promoter regions is correlated with active gene expression.
      Furthermore, knockout of JMJD1B blocks demethylation of H4R3me2s and/or H3K9me2
      at distinct clusters of genes and impairs the activation of genes important for
      HSPC differentiation and development. Consequently, JMJD1B-/- mice show defects
      in hematopoiesis. Altogether, our study demonstrates that demethylase-mediated
      active arginine demethylation process exists in eukaryotes and that JMJD1B
      demethylates both H4R3me2s and H3K9me2 for epigenetic programming during
      hematopoiesis.

PMID- 29642000
TI  - Small-Molecule Targeting of RNA Polymerase I Activates a Conserved Transcription
      Elongation Checkpoint.
AB  - Inhibition of RNA polymerase I (Pol I) is a promising strategy for modern cancer
      therapy. BMH-21 is a first-in-class small molecule that inhibits Pol I
      transcription and induces degradation of the enzyme, but how this exceptional
      response is enforced is not known. Here, we define key elements requisite for the
      response. We show that Pol I preinitiation factors and polymerase subunits (e.g.,
      RPA135) are required for BMH-21-mediated degradation of RPA194. We further find
      that Pol I inhibition and induced degradation by BMH-21 are conserved in yeast.
      Genetic analyses demonstrate that mutations that induce transcription elongation
      defects in Pol I result in hypersensitivity to BMH-21. Using a fully
      reconstituted Pol I transcription assay, we show that BMH-21 directly impairs
      transcription elongation by Pol I, resulting in long-lived polymerase pausing.
      These studies define a conserved regulatory checkpoint that monitors Pol I
      transcription and is activated by therapeutic intervention.

PMID- 29642001
TI  - Functional Genome-wide Screen Identifies Pathways Restricting Central Nervous
      System Axonal Regeneration.
AB  - Axonal regrowth is crucial for recovery from CNS injury but is severely
      restricted in adult mammals. We used a genome-wide loss-of-function screen for
      factors limiting axonal regeneration from cerebral cortical neurons in vitro.
      Knockdown of 16,007 individual genes identified 580 significant phenotypes. These
      molecules share no significant overlap with those suggested by previous
      expression profiles. There is enrichment for genes in pathways related to
      transport, receptor binding, and cytokine signaling, including Socs4 and Ship2.
      Among transport-regulating proteins, Rab GTPases are prominent. In vivo
      assessment with C. elegans validates a cell-autonomous restriction of
      regeneration by Rab27. Mice lacking Rab27b show enhanced retinal ganglion cell
      axon regeneration after optic nerve crush and greater motor function and
      raphespinal sprouting after spinal cord trauma. Thus, a comprehensive functional
      screen reveals multiple pathways restricting axonal regeneration and neurological
      recovery after injury.

PMID- 29642002
TI  - Delineating the Macroscale Areal Organization of the Macaque Cortex In Vivo.
AB  - Complementing long-standing traditions centered on histology, fMRI approaches are
      rapidly maturing in delineating brain areal organization at the macroscale. The
      non-human primate (NHP) provides the opportunity to overcome critical barriers in
      translational research. Here, we establish the data requirements for achieving
      reproducible and internally valid parcellations in individuals. We demonstrate
      that functional boundaries serve as a functional fingerprint of the individual
      animals and can be achieved under anesthesia or awake conditions (rest,
      naturalistic viewing), though differences between awake and anesthetized states
      precluded the detection of individual differences across states. Comparison of
      awake and anesthetized states suggested a more nuanced picture of changes in
      connectivity for higher-order association areas, as well as visual and motor
      cortex. These results establish feasibility and data requirements for the
      generation of reproducible individual-specific parcellations in NHPs, provide
      insights into the impact of scan state, and motivate efforts toward harmonizing
      protocols.

PMID- 29642003
TI  - FOXF1 Inhibits Pulmonary Fibrosis by Preventing CDH2-CDH11 Cadherin Switch in
      Myofibroblasts.
AB  - Idiopathic pulmonary fibrosis (IPF) is characterized by aberrant accumulation of
      collagen-secreting myofibroblasts. Development of effective therapies is limited
      due to incomplete understanding of molecular mechanisms regulating myofibroblast
      expansion. FOXF1 transcription factor is expressed in resident lung fibroblasts,
      but its role in lung fibrosis remains unknown due to the lack of genetic mouse
      models. Through comprehensive analysis of human IPF genomics data, lung biopsies,
      and transgenic mice with fibroblast-specific inactivation of FOXF1, we show that
      FOXF1 inhibits pulmonary fibrosis. FOXF1 deletion increases myofibroblast
      invasion and collagen secretion and promotes a switch from N-cadherin (CDH2) to
      Cadherin-11 (CDH11), which is a critical step in the acquisition of the pro
      fibrotic phenotype. FOXF1 directly binds to Cdh2 and Cdh11 promoters and
      differentially regulates transcription of these genes. Re-expression of CDH2 or
      inhibition of CDH11 in FOXF1-deficient cells reduces myofibroblast invasion in
      vitro. FOXF1 inhibits pulmonary fibrosis by regulating a switch from CDH2 to
      CDH11 in lung myofibroblasts.

PMID- 29642004
TI  - Cardiomyocyte Membrane Structure and cAMP Compartmentation Produce Anatomical
      Variation in beta2AR-cAMP Responsiveness in Murine Hearts.
AB  - Cardiomyocytes from the apex but not the base of the heart increase their
      contractility in response to beta2-adrenoceptor (beta2AR) stimulation, which may
      underlie the development of Takotsubo cardiomyopathy. However, both cell types
      produce comparable cytosolic amounts of the second messenger cAMP. We
      investigated this discrepancy using nanoscale imaging techniques and found that,
      structurally, basal cardiomyocytes have more organized membranes (higher T
      tubular and caveolar densities). Local membrane microdomain responses measured in
      isolated basal cardiomyocytes or in whole hearts revealed significantly smaller
      and more short-lived beta2AR/cAMP signals. Inhibition of PDE4, caveolar
      disruption by removing cholesterol or genetic deletion of Cav3 eliminated
      differences in local cAMP production and equilibrated the contractile response to
      beta2AR. We conclude that basal cells possess tighter control of cAMP because of
      a higher degree of signaling microdomain organization. This provides varying
      levels of nanostructural control for cAMP-mediated functional effects that
      orchestrate macroscopic, regional physiological differences within the heart.

PMID- 29642005
TI  - Mind Bomb Regulates Cell Death during TNF Signaling by Suppressing RIPK1's
      Cytotoxic Potential.
AB  - Tumor necrosis factor (TNF) is an inflammatory cytokine that can signal cell
      survival or cell death. The mechanisms that switch between these distinct
      outcomes remain poorly defined. Here, we show that the E3 ubiquitin ligase Mind
      Bomb-2 (MIB2) regulates TNF-induced cell death by inactivating RIPK1 via
      inhibitory ubiquitylation. Although depletion of MIB2 has little effect on NF
      kappaB activation, it sensitizes cells to RIPK1- and caspase-8-dependent cell
      death. We find that MIB2 represses the cytotoxic potential of RIPK1 by
      ubiquitylating lysine residues in the C-terminal portion of RIPK1. Our data
      suggest that ubiquitin conjugation of RIPK1 interferes with RIPK1 oligomerization
      and RIPK1-FADD association. Disruption of MIB2-mediated ubiquitylation, either by
      mutation of MIB2's E3 activity or RIPK1's ubiquitin-acceptor lysines, sensitizes
      cells to RIPK1-mediated cell death. Together, our findings demonstrate that Mind
      Bomb E3 ubiquitin ligases can function as additional checkpoint of cytokine
      induced cell death, selectively protecting cells from the cytotoxic effects of
      TNF.

PMID- 29642006
TI  - ADAMTS9-Regulated Pericellular Matrix Dynamics Governs Focal Adhesion-Dependent
      Smooth Muscle Differentiation.
AB  - Focal adhesions anchor cells to extracellular matrix (ECM) and direct assembly of
      a pre-stressed actin cytoskeleton. They act as a cellular sensor and regulator,
      linking ECM to the nucleus. Here, we identify proteolytic turnover of the anti
      adhesive proteoglycan versican as a requirement for maintenance of smooth muscle
      cell (SMC) focal adhesions. Using conditional deletion in mice, we show that
      ADAMTS9, a secreted metalloprotease, is required for myometrial activation during
      late gestation and for parturition. Through knockdown of ADAMTS9 in uterine SMC,
      and manipulation of pericellular versican via knockdown or proteolysis, we
      demonstrate that regulated pericellular matrix dynamics is essential for focal
      adhesion maintenance. By influencing focal adhesion formation, pericellular
      versican acts upstream of cytoskeletal assembly and SMC differentiation. Thus,
      pericellular versican proteolysis by ADAMTS9 balances pro- and anti-adhesive
      forces to maintain an SMC phenotype, providing a concrete example of the dynamic
      reciprocity of cells and their ECM.

PMID- 29642007
TI  - How Biophysical Forces Regulate Human B Cell Lymphomas.
AB  - The role of microenvironment-mediated biophysical forces in human lymphomas
      remains elusive. Diffuse large B cell lymphomas (DLBCLs) are heterogeneous
      tumors, which originate from highly proliferative germinal center B cells. These
      tumors, their associated neo-vessels, and lymphatics presumably expose cells to
      particular fluid flow and survival signals. Here, we show that fluid flow
      enhances proliferation and modulates response of DLBCLs to specific therapeutic
      agents. Fluid flow upregulates surface expression of B cell receptors (BCRs) and
      integrin receptors in subsets of ABC-DLBCLs with either CD79A/B mutations or WT
      BCRs, similar to what is observed with xenografted human tumors in mice. Fluid
      flow differentially upregulates signaling targets, such as SYK and p70S6K, in ABC
      DLBCLs. By selective knockdown of CD79B and inhibition of signaling targets, we
      provide mechanistic insights into how fluid flow mechanomodulates BCRs and
      integrins in ABC-DLBCLs. These findings redefine microenvironment factors that
      regulate lymphoma-drug interactions and will be critical for testing targeted
      therapies.

PMID- 29642009
TI  - STIM2 Induces Activated Conformation of STIM1 to Control Orai1 Function in ER-PM
      Junctions.
AB  - Ca2+ entry mediated by the calcium channel, Orai1, provides critical Ca2+ signals
      that regulate cell function. The ER-Ca2+ sensor protein, STIM1, recruits and
      strongly activates Orai1 within ER-PM junctions. STIM2 is a poor activator of
      Orai1, and its physiological role is not well understood. Herein, we report a
      crucial function for STIM2 in inducing the activated conformation of STIM1. By
      using conformational sensors of STIM2 and STIM1, together with protein
      interaction and functional studies, we show that STIM2 is constitutively
      localized within ER-PM junctions in ER-Ca2+ store replete cells. Importantly,
      STIM2 traps STIM1 and triggers remodeling of STIM1 C terminus, causing
      STIM1/Orai1 coupling and enhancement of Orai1 function in cells with relatively
      high ER-[Ca2+]. The increase in Ca2+ entry controls Ca2+-dependent transcription
      factor, NFAT, activation at low [agonist]. Our findings reveal that STIM2
      modulates STIM1/Orai1 function to tune the fidelity of receptor-evoked Ca2+
      signaling and the physiological response of cells.

PMID- 29642008
TI  - Global Cancer Transcriptome Quantifies Repeat Element Polarization between
      Immunotherapy Responsive and T Cell Suppressive Classes.
AB  - It has been posited that anti-tumoral innate activation is driven by derepression
      of endogenous repeats. We compared RNA sequencing protocols to assess repeat
      transcriptomes in The Cancer Genome Atlas (TCGA). Although poly(A) selection
      efficiently detects coding genes, most non-coding genes, and limited subsets of
      repeats, it fails to capture overall repeat expression and co-expression.
      Alternatively, total RNA expression reveals distinct repeat co-expression
      subgroups and delivers greater dynamic changes, implying they may serve as better
      biomarkers of clinical outcomes. We show that endogenous retrovirus expression
      predicts immunotherapy response better than conventional immune signatures in one
      cohort yet is not predictive in another. Moreover, we find that global repeat
      derepression, including the HSATII satellite repeat, correlates with an
      immunosuppressive phenotype in colorectal and pancreatic tumors and validate in
      situ. In conclusion, we stress the importance of analyzing the full spectrum of
      repeat transcription to decode their role in tumor immunity.

PMID- 29642010
TI  - Dual and Direction-Selective Mechanisms of Phosphate Transport by the Vesicular
      Glutamate Transporter.
AB  - Vesicular glutamate transporters (VGLUTs) fill synaptic vesicles with glutamate
      and are thus essential for glutamatergic neurotransmission. However, VGLUTs were
      originally discovered as members of a transporter subfamily specific for
      inorganic phosphate (Pi). It is still unclear how VGLUTs accommodate glutamate
      transport coupled to an electrochemical proton gradient DeltaMUH+ with inversely
      directed Pi transport coupled to the Na+ gradient and the membrane potential.
      Using both functional reconstitution and heterologous expression, we show that
      VGLUT transports glutamate and Pi using a single substrate binding site but
      different coupling to cation gradients. When facing the cytoplasm, both ions are
      transported into synaptic vesicles in a DeltaMUH+-dependent fashion, with
      glutamate preferred over Pi. When facing the extracellular space, Pi is
      transported in a Na+-coupled manner, with glutamate competing for binding but at
      lower affinity. We conclude that VGLUTs have dual functions in both vesicle
      transmitter loading and Pi homeostasis within glutamatergic neurons.

PMID- 29642011
TI  - RNA-Dependent Intergenerational Inheritance of Enhanced Synaptic Plasticity after
      Environmental Enrichment.
AB  - Physical exercise in combination with cognitive training is known to enhance
      synaptic plasticity, learning, and memory and lower the risk for various complex
      diseases including Alzheimer's disease. Here, we show that exposure of adult male
      mice to an environmental enrichment paradigm leads to enhancement of synaptic
      plasticity and cognition also in the next generation. We show that this effect is
      mediated through sperm RNA and especially miRs 212/132. In conclusion, our study
      reports intergenerational inheritance of an acquired cognitive benefit and points
      to specific miRs as candidates mechanistically involved in this type of
      transmission.

PMID- 29642013
TI  - Discovery of Ubiquitin Deamidases in the Pathogenic Arsenal of Legionella
      pneumophila.
AB  - Legionella pneumophila translocates the largest known arsenal of over 330
      pathogenic factors, called "effectors," into host cells during infection,
      enabling L. pneumophila to establish a replicative niche inside diverse amebas
      and human macrophages. Here, we reveal that the L. pneumophila effectors MavC
      (Lpg2147) and MvcA (Lpg2148) are structural homologs of cycle inhibiting factor
      (Cif) effectors and that the adjacent gene, lpg2149, produces a protein that
      directly inhibits their activity. In contrast to canonical Cifs, both MavC and
      MvcA contain an insertion domain and deamidate the residue Gln40 of ubiquitin but
      not Gln40 of NEDD8. MavC and MvcA are functionally diverse, with only MavC
      interacting with the human E2-conjugating enzyme UBE2N (Ubc13). MavC deamidates
      the UBE2N~Ub conjugate, disrupting Lys63 ubiquitination and dampening NF-kappaB
      signaling. Combined, our data reveal a molecular mechanism of host manipulation
      by pathogenic bacteria and highlight the complex regulatory mechanisms integral
      to L. pneumophila's pathogenic strategy.

PMID- 29642012
TI  - Environmental Enrichment and Social Isolation Mediate Neuroplasticity of Medium
      Spiny Neurons through the GSK3 Pathway.
AB  - Resilience and vulnerability to neuropsychiatric disorders are linked to
      molecular changes underlying excitability that are still poorly understood. Here,
      we identify glycogen-synthase kinase 3beta (GSK3beta) and voltage-gated Na+
      channel Nav1.6 as regulators of neuroplasticity induced by environmentally
      enriched (EC) or isolated (IC) conditions-models for resilience and
      vulnerability. Transcriptomic studies in the nucleus accumbens from EC and IC
      rats predicted low levels of GSK3beta and SCN8A mRNA as a protective phenotype
      associated with reduced excitability in medium spiny neurons (MSNs). In vivo
      genetic manipulations demonstrate that GSK3beta and Nav1.6 are molecular
      determinants of MSN excitability and that silencing of GSK3beta prevents
      maladaptive plasticity of IC MSNs. In vitro studies reveal direct interaction of
      GSK3beta with Nav1.6 and phosphorylation at Nav1.6T1936 by GSK3beta. A GSK3beta
      Nav1.6T1936 competing peptide reduces MSNs excitability in IC, but not EC rats.
      These results identify GSK3beta regulation of Nav1.6 as a biosignature of MSNs
      maladaptive plasticity.

PMID- 29642014
TI  - A Universal Approach to Optimize the Folding and Stability of Prefusion-Closed
      HIV-1 Envelope Trimers.
AB  - The heavily glycosylated native-like envelope (Env) trimer of HIV-1 is expected
      to have low immunogenicity, whereas misfolded forms are often highly immunogenic.
      High-quality correctly folded Envs may therefore be critical for developing a
      vaccine that induces broadly neutralizing antibodies. Moreover, the high
      variability of Env may require immunizations with multiple Envs. Here, we report
      a universal strategy that provides for correctly folded Env trimers of high
      quality and yield through a repair-and-stabilize approach. In the repair stage,
      we utilized a consensus strategy that substituted rare strain-specific residues
      with more prevalent ones. The stabilization stage involved structure-based design
      and experimental assessment confirmed by crystallographic feedback. Regions
      important for the refolding of Env were targeted for stabilization. Notably, the
      alpha9-helix and an intersubunit beta sheet proved to be critical for trimer
      stability. Our approach provides a means to produce prefusion-closed Env trimers
      from diverse HIV-1 strains, a substantial advance for vaccine development.

PMID- 29642016
TI  - Genome-wide Translation Profiling by Ribosome-Bound tRNA Capture.
AB  - In the ribosome complex, tRNA is a critical element of mRNA translation. A rich
      repertoire of cell regulation is hypothesized to occur during the recruitment of
      specific tRNAs in polypeptide formation. However, this basic question in nascent
      chain biology remains unaddressed due to the lack of technologies to report the
      complete tRNA complement inside ribosomes during active translation. Here, we
      characterize a technique for profiling ribosome-embedded tRNA and their
      modifications. With this method, we generated a comprehensive survey of the
      quantity and quality of intra-ribosomal tRNAs. In cells under environmental
      stress, we show that methionine tRNA inside ribosomes is a robust biomarker for
      the impairment of translation initiation or elongation steps. Concurrent
      tRNA/mRNA ribosome profiling revealed a stress-dependent incorporation of damaged
      and uncharged tRNAs into ribosomes causing translation arrest. Thus, tRNA
      ribosome profiling can provide insights on translation control mechanisms in
      diverse biological contexts.

PMID- 29642015
TI  - Genome-wide CRISPR/Cas9 Screen Identifies Host Factors Essential for Influenza
      Virus Replication.
AB  - The emergence of influenza A viruses (IAVs) from zoonotic reservoirs poses a
      great threat to human health. As seasonal vaccines are ineffective against
      zoonotic strains, and newly transmitted viruses can quickly acquire drug
      resistance, there remains a need for host-directed therapeutics against IAVs.
      Here, we performed a genome-scale CRISPR/Cas9 knockout screen in human lung
      epithelial cells with a human isolate of an avian H5N1 strain. Several genes
      involved in sialic acid biosynthesis and related glycosylation pathways were
      highly enriched post-H5N1 selection, including SLC35A1, a sialic acid transporter
      essential for IAV receptor expression and thus viral entry. Importantly, we have
      identified capicua (CIC) as a negative regulator of cell-intrinsic immunity, as
      loss of CIC resulted in heightened antiviral responses and restricted replication
      of multiple viruses. Therefore, our study demonstrates that the CRISPR/Cas9
      system can be utilized for the discovery of host factors critical for the
      replication of intracellular pathogens.

PMID- 29642017
TI  - Deciphering the Dynamic Transcriptional and Post-transcriptional Networks of
      Macrophages in the Healthy Heart and after Myocardial Injury.
AB  - Macrophage plasticity has been studied in vitro, but transcriptional regulation
      upon injury is poorly understood. We generated a valuable dataset that captures
      transcriptional changes in the healthy heart and after myocardial injury,
      revealing a dynamic transcriptional landscape of macrophage activation. Partial
      deconvolution suggested that post-injury macrophages exhibit overlapping
      activation of pro-inflammatory and anti-inflammatory programs rather than
      aligning to canonical M1/M2 programs. Furthermore, simulated dynamics and
      experimental validation of a regulatory core of the underlying gene-regulatory
      network revealed a negative-feedback loop that limits initial inflammation via
      hypoxia-mediated upregulation of Il10. Our results also highlight the prominence
      of post-transcriptional regulation (miRNAs, mRNA decay, and lincRNAs) in
      attenuating the myocardial injury-induced inflammatory response. We also
      identified a cardiac-macrophage-specific gene signature (e.g., Egfr and Lifr) and
      time-specific markers for macrophage populations (e.g., Lyve1, Cd40, and Mrc1).
      Altogether, these data provide a core resource for deciphering the
      transcriptional network in cardiac macrophages in vivo.

PMID- 29642018
TI  - A Distinct DNA Methylation Shift in a Subset of Glioma CpG Island Methylator
      Phenotypes during Tumor Recurrence.
AB  - Glioma diagnosis is based on histomorphology and grading; however, such
      classification does not have predictive clinical outcome after glioblastomas have
      developed. To date, no bona fide biomarkers that significantly translate into a
      survival benefit to glioblastoma patients have been identified. We previously
      reported that the IDH mutant G-CIMP-high subtype would be a predecessor to the G
      CIMP-low subtype. Here, we performed a comprehensive DNA methylation longitudinal
      analysis of diffuse gliomas from 77 patients (200 tumors) to enlighten the
      epigenome-based malignant transformation of initially lower-grade gliomas. Intra
      subtype heterogeneity among G-CIMP-high primary tumors allowed us to identify
      predictive biomarkers for assessing the risk of malignant recurrence at early
      stages of disease. G-CIMP-low recurrence appeared in 9.5% of all gliomas, and
      these resembled IDH-wild-type primary glioblastoma. G-CIMP-low recurrence can be
      characterized by distinct epigenetic changes at candidate functional tissue
      enhancers with AP-1/SOX binding elements, mesenchymal stem cell-like epigenomic
      phenotype, and genomic instability. Molecular abnormalities of longitudinal G
      CIMP offer possibilities to defy glioblastoma progression.

PMID- 29642020
TI  - A nonnegative matrix factorization algorithm based on a discrete-time projection
      neural network.
AB  - This paper presents an algorithm for nonnegative matrix factorization based on a
      biconvex optimization formulation. First, a discrete-time projection neural
      network is introduced. An upper bound of its step size is derived to guarantee
      the stability of the neural network. Then, an algorithm is proposed based on the
      discrete-time projection neural network and a backtracking step-size adaptation.
      The proposed algorithm is proven to be able to reduce the objective function
      value iteratively until attaining a partial optimum of the formulated biconvex
      optimization problem. Experimental results based on various data sets are
      presented to substantiate the efficacy of the algorithm.

PMID- 29642021
TI  - A Dual Regulatory Role for the Disordered C-Terminus of Protein Kinase Calpha.

PMID- 29642019
TI  - A Genetic Toolkit for Dissecting Dopamine Circuit Function in Drosophila.
AB  - The neuromodulator dopamine (DA) plays a key role in motor control, motivated
      behaviors, and higher-order cognitive processes. Dissecting how these DA neural
      networks tune the activity of local neural circuits to regulate behavior requires
      tools for manipulating small groups of DA neurons. To address this need, we
      assembled a genetic toolkit that allows for an exquisite level of control over
      the DA neural network in Drosophila. To further refine targeting of specific DA
      neurons, we also created reagents that allow for the conversion of any existing
      GAL4 line into Split GAL4 or GAL80 lines. We demonstrated how this toolkit can be
      used with recently developed computational methods to rapidly generate additional
      reagents for manipulating small subsets or individual DA neurons. Finally, we
      used the toolkit to reveal a dynamic interaction between a small subset of DA
      neurons and rearing conditions in a social space behavioral assay.

PMID- 29642022
TI  - Interacting Bacteria Surfaces.

PMID- 29642023
TI  - PAM: A Framework for Integrated Analysis of Imaging, Single-Molecule, and
      Ensemble Fluorescence Data.
AB  - Fluorescence microscopy and spectroscopy data hold a wealth of information on the
      investigated molecules, structures, or organisms. Nowadays, the same fluorescence
      data set can be analyzed in many ways to extract different properties of the
      measured sample. Yet, doing so remains slow and cumbersome, often requiring
      incompatible software packages. Here, we present PAM (pulsed interleaved
      excitation analysis with MATLAB), an open-source software package written in
      MATLAB that offers a simple and efficient workflow through its graphical user
      interface. PAM is a framework for integrated and robust analysis of fluorescence
      ensemble, single-molecule, and imaging data. Although it was originally developed
      for the analysis of pulsed interleaved excitation experiments, PAM has since been
      extended to support most types of data collection modalities. It combines a
      multitude of powerful analysis algorithms, ranging from time- and space
      correlation analysis, over single-molecule burst analysis, to lifetime imaging
      microscopy, while offering intrinsic support for multicolor experiments. We
      illustrate the key concepts and workflow of the software by discussing data
      handling and sorting and provide step-by-step descriptions for the individual
      usage cases.

PMID- 29642024
TI  - Fast-Folding Pathways of the Thrombin-Binding Aptamer G-Quadruplex Revealed by a
      Markov State Model.
AB  - G-quadruplex structures participate in many important cellular processes. For a
      better understanding of their functions, knowledge of the mechanism by which they
      fold into the functional native structures is necessary. In this work, we studied
      the folding process of the thrombin-binding aptamer G-quadruplex. Enabled by a
      computational paradigm that couples an advanced sampling method and a Markov
      state model, four folding intermediates were identified, including an
      antiparallel G-hairpin, two G-triplex structures, and a double-hairpin
      conformation. Likewise, a misfolded structure with a nonnative distribution of
      syn/anti guanines was also observed. Based on these states, a transition path
      analysis revealed three fast-folding pathways, along which the thrombin-binding
      aptamer would fold to the native state directly, with no evidence of potential
      nonnative competing conformations. The results also showed that the TGT-loop
      plays an important role in the folding process. The findings of this research may
      provide general insight about the folding of other G-quadruplex structures.

PMID- 29642026
TI  - Preferential Binding of Urea to Single-Stranded DNA Structures: A Molecular
      Dynamics Study.
AB  - In nature, a wide range of biological processes such as transcription termination
      and intermolecular binding depend on the formation of specific DNA secondary and
      tertiary structures. These structures can be both stabilized or destabilized by
      different cosolutes coexisting with nucleic acids in the cellular environment. In
      our molecular dynamics simulation study, we investigate the binding of urea at
      different concentrations to short 7-nucleotide single-stranded DNA structures in
      aqueous solution. The local concentration of urea around a native DNA hairpin in
      comparison to an unfolded DNA conformation is analyzed by a preferential binding
      model in light of the Kirkwood-Buff theory. All our findings indicate a
      pronounced accumulation of urea around DNA that is driven by a combination of
      electrostatic and dispersion interactions and accomplished by a significant
      replacement of hydrating water molecules. The outcomes of our study can be
      regarded as a first step into a deeper mechanistic understanding toward cosolute
      induced effects on nucleotide structures in general.

PMID- 29642025
TI  - Measurement of Mesoscale Conformational Dynamics of Freely Diffusing Molecules
      with Tracking FCS.
AB  - Few techniques are suited to probe the structure and dynamics of molecular
      complexes at the mesoscale level (~100-1000 nm). We have developed a single
      molecule technique that uses tracking fluorescence correlation spectroscopy
      (tFCS) to probe the conformation and dynamics of mesoscale molecular assemblies.
      tFCS measures the distance fluctuations between two fluorescently labeled sites
      within an untethered, freely diffusing biomolecule. To achieve subdiffraction
      spatial resolution, we developed a feedback scheme that allows us to maintain the
      molecule at an optimal position within the laser intensity gradient for
      fluorescence correlation spectroscopy. We characterized tFCS spatial sensitivity
      by measuring the Brownian end-to-end dynamics of DNA molecules as short as 1000
      bp. We demonstrate that tFCS detects changes in the compaction of reconstituted
      nucleosome arrays and can assay transient protein-mediated interactions between
      distant sites in an individual DNA molecule. Our measurements highlight the
      applicability of tFCS to a wide variety of biochemical processes involving
      mesoscale conformational dynamics.

PMID- 29642027
TI  - Modeling the Early Stages of Phase Separation in Disordered Elastin-like
      Proteins.
AB  - Elastin-like proteins (ELPs) are known to undergo liquid-liquid phase separation
      reversibly above a concentration-dependent transition temperature. Previous
      studies suggested that, as temperature increases, ELPs experience an increased
      propensity for type II beta-turns. However, how the ELPs behave below the phase
      transition temperature itself is still elusive. Here, we investigate the
      importance of beta-turn formation during the early stages of ELP self
      association. We examined the behavior of two ELPs, a 150-repeat construct that
      had been investigated previously (ELP[V5G3A2-150] as well as a new 40-repeat
      construct (ELP40) suitable for nuclear magnetic resonance measurements.
      Structural analysis of ELP40 reveals a disordered conformation, and chemical
      shifts throughout the sequence are insensitive to changes in temperature over 20
      degrees C. However, a low population of beta-turn conformation cannot be ruled
      out based on chemical shifts alone. To examine the structural consequences of
      beta-turns in ELPs, a series of structural ensembles of ELP[V5G3A2-150] were
      generated, incorporating differing amounts of beta-turn bias throughout the
      chain. To mimic the early stages of the phase change, two monomers were paired,
      assuming preferential interaction at beta-turn regions. This approach was
      justified by the observation that buried hydrophobic turns are commonly observed
      to interact in the Protein Data Bank. After dimerization, the ensemble-averaged
      hydrodynamic properties were calculated for each degree of beta-turn bias, and
      the results were compared with analytical ultracentrifugation experiments at
      various temperatures. We find that the temperature dependence of the
      sedimentation coefficient (s20,wo) can be reproduced by increasing the beta-turn
      content in the structural ensemble. This analysis allows us to estimate the
      presence of beta-turns and weak associations under experimental conditions.
      Because disordered proteins frequently exhibit weak biases in secondary structure
      propensity, these experimentally-driven ensemble calculations may complement
      existing methods for modeling disordered proteins generally.

PMID- 29642028
TI  - Unwinding of the Substrate Transmembrane Helix in Intramembrane Proteolysis.
AB  - Intramembrane-cleaving proteases (I-CLiPs) activate pools of single-pass helical
      membrane protein signaling precursors that are key in the physiology of
      prokaryotic and eukaryotic cells. Proteases typically cleave peptide bonds within
      extended or flexible regions of their substrates, and thus the mechanism
      underlying the ability of I-CLiPs to hydrolyze the presumably alpha-helical
      transmembrane domain (TMD) of these membrane proteins is unclear. Using deep
      ultraviolet resonance Raman spectroscopy in combination with isotopic labeling,
      we show that although predominantly in canonical alpha-helical conformation, the
      TMD of the established I-CLiP substrate Gurken displays 310-helical geometry. As
      measured by microscale thermophoresis, this substrate binds with high affinity to
      the I-CLiPs GlpG rhomboid and MCMJR1 presenilin homolog in detergent micelles.
      Binding results in deep-ultraviolet resonance Raman spectra, indicating
      conformational changes consistent with unwinding of the 310-helical region of the
      substrate's TMD. This 310-helical conformation is key for intramembrane
      proteolysis, as the substitution of a single proline residue in the TMD of Gurken
      by alanine suppresses 310-helical content in favor of alpha-helical geometry and
      abolishes cleavage without affecting binding to the I-CLiP. Complemented by
      molecular dynamics simulations of the TMD of Gurken, our vibrational spectroscopy
      data provide biophysical evidence in support of a model in which the
      transmembrane region of cleavable I-CLiP substrates displays local deviations in
      canonical alpha-helical conformation characterized by chain flexibility, and
      binding to the enzyme results in conformational changes that facilitate local
      unwinding of the transmembrane helix for cleavage.

PMID- 29642029
TI  - Structural Basis of Protein Kinase Calpha Regulation by the C-Terminal Tail.
AB  - Protein kinase C (PKC) isoenzymes are multi-modular proteins activated at the
      membrane surface to regulate signal transduction processes. When activated by
      second messengers, PKC undergoes a drastic conformational and spatial transition
      from the inactive cytosolic state to the activated membrane-bound state. The
      complete structure of either state of PKC remains elusive. We demonstrate, using
      NMR spectroscopy, that the isolated Ca2+-sensing membrane-binding C2 domain of
      the conventional PKCalpha interacts with a conserved hydrophobic motif of the
      kinase C-terminal region, and we report a structural model of the complex. Our
      data suggest that the C-terminal region plays a dual role in regulating the PKC
      activity: activating, through sensitization of PKC to intracellular Ca2+
      oscillations; and auto-inhibitory, through its interaction with a conserved
      positively charged region of the C2 domain.

PMID- 29642030
TI  - Simultaneous Determination of Protein Structure and Dynamics Using Cryo-Electron
      Microscopy.
AB  - Cryo-electron microscopy is rapidly emerging as a powerful technique to determine
      the structures of complex macromolecular systems elusive to other techniques.
      Because many of these systems are highly dynamical, characterizing their
      movements is also a crucial step to unravel their biological functions. To
      achieve this goal, we report an integrative modeling approach to simultaneously
      determine structure and dynamics of macromolecular systems from cryo-electron
      microscopy density maps. By quantifying the level of noise in the data and
      dealing with their ensemble-averaged nature, this approach enables the
      integration of multiple sources of information to model ensembles of structures
      and infer their populations. We illustrate the method by characterizing structure
      and dynamics of the integral membrane receptor STRA6, thus providing insights
      into the mechanisms by which it interacts with retinol binding protein and
      translocates retinol across the membrane.

PMID- 29642031
TI  - DNP-Enhanced MAS NMR: A Tool to Snapshot Conformational Ensembles of alpha
      Synuclein in Different States.
AB  - Intrinsically disordered proteins dynamically sample a wide conformational space
      and therefore do not adopt a stable and defined three-dimensional conformation.
      The structural heterogeneity is related to their proper functioning in
      physiological processes. Knowledge of the conformational ensemble is crucial for
      a complete comprehension of this kind of proteins. We here present an approach
      that utilizes dynamic nuclear polarization-enhanced solid-state NMR spectroscopy
      of sparsely isotope-labeled proteins in frozen solution to take snapshots of the
      complete structural ensembles by exploiting the inhomogeneously broadened line
      shapes. We investigated the intrinsically disordered protein alpha-synuclein
      (alpha-syn), which plays a key role in the etiology of Parkinson's disease, in
      three different physiologically relevant states. For the free monomer in frozen
      solution we could see that the so-called "random coil conformation" consists of
      alpha-helical and beta-sheet-like conformations, and that secondary chemical
      shifts of neighboring amino acids tend to be correlated, indicative of frequent
      formation of secondary structure elements. Based on these results, we could
      estimate the number of disordered regions in fibrillar alpha-syn as well as in
      alpha-syn bound to membranes in different protein-to-lipid ratios. Our approach
      thus provides quantitative information on the propensity to sample transient
      secondary structures in different functional states. Molecular dynamics
      simulations rationalize the results.

PMID- 29642032
TI  - Conformation of Single and Interacting Lipopolysaccharide Surfaces Bearing O-Side
      Chains.
AB  - The outer surfaces of Gram-negative bacteria are composed of lipopolysaccharide
      (LPS) molecules exposing oligo- and polysaccharides to the aqueous environment.
      This unique, structurally complex biological interface is of great scientific
      interest as it mediates the interaction of bacteria with antimicrobial agents as
      well as with neighboring bacteria in colonies and biofilms. Structural studies on
      LPS surfaces, however, have so far dealt almost exclusively with rough mutant LPS
      of reduced molecular complexity and limited biological relevance. Here, by using
      neutron reflectometry, we structurally characterize planar monolayers of wild
      type LPS from Escherichia coli O55:B5 featuring strain-specific O-side chains in
      the presence and absence of divalent cations and under controlled interaction
      conditions. The model used for the reflectivity analysis is self-consistent and
      based on the volume fraction profiles of all chemical components. The saccharide
      profiles are found to be bimodal, with dense inner oligosaccharides and more
      dilute, extended O-side chains. For interacting LPS monolayers, we establish the
      pressure-distance curve and determine the distance-dependent saccharide
      conformation.

PMID- 29642033
TI  - Partitioning and Enhanced Self-Assembly of Actin in Polypeptide Coacervates.
AB  - Biomolecules exist and function in cellular microenvironments that control their
      spatial organization, local concentration, and biochemical reactivity. Due to the
      complexity of native cytoplasm, the development of artificial bioreactors and
      cellular mimics to compartmentalize, concentrate, and control the local physico
      chemical properties is of great interest. Here, we employ self-assembling
      polypeptide coacervates to explore the partitioning of the ubiquitous
      cytoskeletal protein actin into liquid polymer-rich droplets. We find that actin
      spontaneously partitions into coacervate droplets and is enriched by up to ~30
      fold. Actin polymerizes into micrometer-long filaments and, in contrast to the
      globular protein BSA, these filaments localize predominately to the droplet
      periphery. We observe up to a 50-fold enhancement in the actin filament assembly
      rate inside coacervate droplets, consistent with the enrichment of actin within
      the coacervate phase. Together these results suggest that coacervates can serve
      as a versatile platform in which to localize and enrich biomolecules to study
      their reactivity in physiological environments.

PMID- 29642034
TI  - TnI Structural Interface with the N-Terminal Lobe of TnC as a Determinant of
      Cardiac Contractility.
AB  - The heterotrimeric cardiac troponin complex is a key regulator of contraction and
      plays an essential role in conferring Ca2+ sensitivity to the sarcomere. During
      ischemic injury, rapidly accumulating protons acidify the myoplasm, resulting in
      markedly reduced Ca2+ sensitivity of the sarcomere. Unlike the adult heart,
      sarcomeric Ca2+ sensitivity in fetal cardiac tissue is comparatively pH
      insensitive. Replacement of the adult cardiac troponin I (cTnI) isoform with the
      fetal troponin I (ssTnI) isoform renders adult cardiac contractile machinery
      relatively insensitive to acidification. Alignment and functional studies have
      determined histidine 132 of ssTnI to be the predominant source of this pH
      insensitivity. Substitution of histidine at the cognate position 164 in cTnI
      confers the same pH insensitivity to adult cardiac myocytes. An alanine at
      position 164 of cTnI is conserved in all mammals, with the exception of the
      platypus, which expresses a proline. Prolines are biophysically unique because of
      their innate conformational rigidity and helix-disrupting function. To provide
      deeper structure-function insight into the role of the TnC-TnI interface in
      determining contractility, we employed a live-cell approach alongside molecular
      dynamics simulations to ascertain the chemo-mechanical implications of the
      disrupted helix 4 of cTnI where position 164 exists. This important motif belongs
      to the critical switch region of cTnI. Substitution of a proline at position 164
      of cTnI in adult rat cardiac myocytes causes increased contractility independent
      of alterations in the Ca2+ transient. Free-energy perturbation calculations of
      cTnC-Ca2+ binding indicate no difference in cTnC-Ca2+ affinity. Rather, we
      propose the enhanced contractility is derived from new salt bridge interactions
      between cTnI helix 4 and cTnC helix A, which are critical in determining pH
      sensitivity and contractility. Molecular dynamics simulations demonstrate that
      cTnI A164P structurally phenocopies ssTnI under baseline but not acidotic
      conditions. These findings highlight the evolutionarily directed role of the TnI
      cTnC interface in determining cardiac contractility.

PMID- 29642035
TI  - Probing Position-Dependent Diffusion in Folding Reactions Using Single-Molecule
      Force Spectroscopy.
AB  - Folding of proteins and nucleic acids involves a diffusive search over a
      multidimensional conformational energy landscape for the minimal-energy
      structure. When examining the projection of conformational motions onto a one
      dimensional reaction coordinate, as done in most experiments, the diffusion
      coefficient D is generally position dependent. However, it has proven challenging
      to measure such position-dependence experimentally. We investigated the position
      dependence of D in the folding of DNA hairpins as a simple model system in two
      ways: first, by analyzing the round-trip time to return to a given extension in
      constant-force extension trajectories measured by force spectroscopy, and second,
      by analyzing the fall time required to reach a given extension in force jump
      measurements. These methods yielded conflicting results: the fall time implied a
      fairly constant D, but the round-trip time implied variations of over an order of
      magnitude. Comparison of experiments with computational simulations revealed that
      both methods were strongly affected by experimental artifacts inherent to force
      spectroscopy measurements, which obscured the intrinsic position-dependence of D.
      Lastly, we applied Kramers's theory to the kinetics of hairpins with energy
      barriers located at different positions along the hairpin stem, as a crude probe
      of D at different stem positions, and we found that D did not vary much as the
      barrier was moved along the reaction coordinate. This work underlines the
      difficulties faced when trying to deduce position-dependent diffusion
      coefficients from experimental folding trajectories.

PMID- 29642036
TI  - Active Mechanics Reveal Molecular-Scale Force Kinetics in Living Oocytes.
AB  - Active diffusion of intracellular components is emerging as an important process
      in cell biology. This process is mediated by complex assemblies of molecular
      motors and cytoskeletal filaments that drive force generation in the cytoplasm
      and facilitate enhanced motion. The kinetics of molecular motors have been
      precisely characterized in vitro by single molecule approaches, but their in vivo
      behavior remains elusive. Here, we study the active diffusion of vesicles in
      mouse oocytes, where this process plays a key role in nuclear positioning during
      development, and combine an experimental and theoretical framework to extract
      molecular-scale force kinetics (force, power stroke, and velocity) of the in vivo
      active process. Assuming a single dominant process, we find that the
      nonequilibrium activity induces rapid kicks of duration tau ~ 300 MUs resulting
      in an average force of F ~ 0.4 pN on vesicles in in vivo oocytes, remarkably
      similar to the kinetics of in vitro myosin-V. Our results reveal that measuring
      in vivo active fluctuations allows extraction of the molecular-scale activity in
      agreement with single-molecule studies and demonstrates a mesoscopic framework to
      access force kinetics.

PMID- 29642037
TI  - Vinculin Force-Sensitive Dynamics at Focal Adhesions Enable Effective Directed
      Cell Migration.
AB  - Cell migration is a complex process, requiring coordination of many subcellular
      processes including membrane protrusion, adhesion, and contractility. For
      efficient cell migration, cells must concurrently control both transmission of
      large forces through adhesion structures and translocation of the cell body via
      adhesion turnover. Although mechanical regulation of protein dynamics has been
      proposed to play a major role in force transmission during cell migration, the
      key proteins and their exact roles are not completely understood. Vinculin is an
      adhesion protein that mediates force-sensitive processes, such as adhesion
      assembly under cytoskeletal load. Here, we elucidate the mechanical regulation of
      vinculin dynamics. Specifically, we paired measurements of vinculin loads using a
      Forster resonance energy transfer-based tension sensor and vinculin dynamics
      using fluorescence recovery after photobleaching to measure force-sensitive
      protein dynamics in living cells. We find that vinculin adopts a variety of
      mechanical states at adhesions, and the relationship between vinculin load and
      vinculin dynamics can be altered by the inhibition of vinculin binding to talin
      or actin or reduction of cytoskeletal contractility. Furthermore, the force
      stabilized state of vinculin required for the stabilization of membrane
      protrusions is unnecessary for random migration, but is required for directional
      migration along a substrate-bound cue. These data show that the force-sensitive
      dynamics of vinculin impact force transmission and enable the mechanical
      integration of subcellular processes. These results suggest that the regulation
      of force-sensitive protein dynamics may have an underappreciated role in many
      cellular processes.

PMID- 29642038
TI  - Evidence against a Role of Elevated Intracellular Ca2+ during Plasmodium
      falciparum Preinvasion.
AB  - Severe malaria is primarily caused by Plasmodium falciparum parasites during
      their asexual reproduction cycle within red blood cells. One of the least
      understood stages in this cycle is the brief preinvasion period during which
      merozoite-red cell contacts lead to apical alignment of the merozoite in
      readiness for penetration, a stage of major relevance in the control of invasion
      efficiency. Red blood cell deformations associated with this process were
      suggested to be active plasma membrane responses mediated by transients of
      elevated intracellular calcium. Few studies have addressed this hypothesis
      because of technical challenges, and the results remained inconclusive. Here,
      Fluo-4 was used as a fluorescent calcium indicator with optimized protocols to
      investigate the distribution of the dye in red blood cell populations used as P.
      falciparum invasion targets in egress-invasion assays. Preinvasion dynamics was
      observed simultaneously under bright-field and fluorescence microscopy by
      recording egress-invasion events. All the egress-invasion sequences showed red
      blood cell deformations of varied intensities during the preinvasion period and
      the echinocytic changes that follow during invasion. Intraerythrocytic calcium
      signals were absent throughout this interval in over half the records and totally
      absent during the preinvasion period, regardless of deformation strength. When
      present, calcium signals were of a punctate modality, initiated within merozoites
      already poised for invasion. These results argue against a role of elevated
      intracellular calcium during the preinvasion stage. We suggest an alternative
      mechanism of merozoite-induced preinvasion deformations based on passive red cell
      responses to transient agonist-receptor interactions associated with the
      formation of adhesive coat filaments.

PMID- 29642039
TI  - Cell-Cell Adhesion and Cortical Actin Bending Govern Cell Elongation on
      Negatively Curved Substrates.
AB  - Physiologically, cells experience and respond to a variety of mechanical stimuli
      such as rigidity and topography of the extracellular matrix. However, little is
      known about the effects of substrate curvature on cell behavior. We developed a
      novel, to our knowledge, method to fabricate cell culture substrates with
      semicylindrical grooves of negative curvatures (radius of curvature, Rc = 20-100
      MUm). We found that negative substrate curvatures induced elongation of
      mesenchymal and epithelial cells along the cylinder axis. As Rc decreases,
      mesenchymal National Institutes of Health 3T3 fibroblasts increasingly elongate
      along the long axis of the grooves, whereas elongation of epithelial Madin-Darby
      Canine Kidney (MDCK) cells is biphasic with maximal cell elongation when Rc = 40
      MUm. Addition of blebbistatin to MDCK cells to reduce cortical actin rigidity
      resulted in a decrease in cell elongation across all curvatures while preserving
      the biphasic trend. However, addition of calyculin A or ethylene glycol-bis(2
      aminoethylether)-N,N,N',N'-tetraacetic acid, to increase cortical rigidity or
      reduce intercellular adhesion, respectively, resulted in a monotonic increase in
      MDCK cell elongation with decreasing Rc. Using an energy minimization model, we
      showed that cell elongation in epithelial cell sheet is governed by the
      competition between two energies as Rc decreases: curvature-dependent
      intercellular adhesion that prevents elongation; and intracellular cortical actin
      bending that enhances elongation. Therefore, our results of cellular elongation
      induced by negatively curved substrates offer insights into how tubule elongation
      or growth of tubular structures such as kidney tubules can be controlled by the
      substrate curvature in vivo.

PMID- 29642040
TI  - Effects of mRNA Degradation and Site-Specific Transcriptional Pausing on Protein
      Expression Noise.
AB  - Genetically identical cells exhibit diverse phenotypes even when experiencing the
      same environment. This phenomenon in part originates from cell-to-cell
      variability (noise) in protein expression. Although various kinetic schemes of
      stochastic transcription initiation are known to affect gene expression noise,
      how posttranscription initiation events contribute to noise at the protein level
      remains incompletely understood. To address this question, we developed a
      stochastic simulation-based model of bacterial gene expression that integrates
      well-known dependencies between transcription initiation, transcription
      elongation dynamics, mRNA degradation, and translation. We identified realistic
      conditions under which mRNA lifetime and transcriptional pauses modulate the
      protein expression noise initially introduced by the promoter architecture. For
      instance, we found that the short lifetime of bacterial mRNAs facilitates the
      production of protein bursts. Conversely, RNA polymerase (RNAP) pausing at
      specific sites during transcription elongation can attenuate protein bursts by
      fluidizing the RNAP traffic to the point of erasing the effect of a bursty
      promoter. Pause-prone sites, if located close to the promoter, can also affect
      noise indirectly by reducing both transcription and translation initiation due to
      RNAP and ribosome congestion. Our findings highlight how the interplay between
      transcription initiation, transcription elongation, translation, and mRNA
      degradation shapes the distribution in protein numbers. They also have
      implications for our understanding of gene evolution and suggest combinatorial
      strategies for modulating phenotypic variability by genetic engineering.

PMID- 29642041
TI  - Mechanical Model of Nuclei Ordering in Drosophila Embryos Reveals Dilution of
      Stochastic Forces.
AB  - During the initial development of syncytial embryos, nuclei go through cycles of
      nuclear division and spatial rearrangement. The arising spatial pattern of nuclei
      is important for subsequent cellularization and morphing of the embryo. Although
      nuclei are contained within a common cytoplasm, cytoskeletal proteins are
      nonuniformly packaged into regions around every nucleus. In fact, cytoskeletal
      elements like microtubules and their associated motor proteins exert stochastic
      forces between nuclei, actively driving their rearrangement. Yet, it is unknown
      how the stochastic forces are balanced to maintain nuclear order in light of
      increased nuclear density upon every round of divisions. Here, we investigate the
      nuclear arrangements in Drosophila melanogaster over the course of several
      nuclear divisions starting from interphase 11. We develop a theoretical model in
      which we distinguish long-ranged passive forces due to the nuclei as inclusions
      in the elastic matrix, namely the cytoplasm, and active, stochastic forces
      arising from the cytoskeletal dynamics mediated by motor proteins. We perform
      computer simulations and quantify the observed degree of orientational and
      spatial order of nuclei. Solely doubling the nuclear density upon nuclear
      division, the model predicts a decrease in nuclear order. Comparing results to
      experimental recordings of tracked nuclei, we make contradictory observations,
      finding an increase in nuclear order upon nuclear divisions. Our analysis of
      model parameters resulting from this comparison suggests that overall motor
      protein density as well as relative active-force amplitude has to decrease by a
      factor of about two upon nuclear division to match experimental observations. We
      therefore expect a dilution of cytoskeletal motors during the rapid nuclear
      division to account for the increase in nuclear order during syncytial embryo
      development. Experimental measurements of kinesin-5 cluster lifetimes support
      this theoretical finding.

PMID- 29642042
TI  - Coexistence and Pattern Formation in Bacterial Mixtures with Contact-Dependent
      Killing.
AB  - Multistrain microbial communities often exhibit complex spatial organization that
      emerges because of the interplay of various cooperative and competitive
      interaction mechanisms. One strong competitive mechanism is contact-dependent
      neighbor killing enabled by the type VI secretion system. It has been previously
      shown that contact-dependent killing can result in bistability of bacterial
      mixtures so that only one strain survives and displaces the other. However, it
      remains unclear whether stable coexistence is possible in such mixtures. Using a
      population dynamics model for two interacting bacterial strains, we found that
      coexistence can be made possible by the interplay of contact-dependent killing
      and long-range growth inhibition, leading to the formation of various cellular
      patterns. These patterns emerge in a much broader parameter range than that
      required for the linear Turing-like instability, suggesting this may be a robust
      mechanism for pattern formation.

PMID- 29642043
TI  - CPEB4 regulates glioblastoma cell proliferation and predicts poor outcome of
      patients.
AB  - OBJECTIVE: Cytoplasmic polyadenylation element binding protein 4 (CPEB4) is a
      regulator of gene expression at transcriptional level and has been reported to be
      associated with biological malignancy in cancers. However, little was known about
      the correlation between CPEB4 and glioblastoma cell proliferation and the
      prognostic significance in patients. Our aim was to investigate the functional
      role and prognostic value of CPEB4 in glioblastoma. PATIENTS AND METHODS: We
      determined the expression of CPEB4 protein using immunohistochemistry in tissue
      microarrays containing 278 glioma patients (including 98 primary glioblastomas)
      and evaluated its association with pathological grades and clinical outcome by
      univariate and multivariate analyses. And then, lentiviral-mediated RNAi
      targeting CPEB4 was utilized to study the role of CPEB4 in glioblastoma cell
      proliferation. RESULTS: In our cohort, CPEB4 expression was positively related to
      glioma pathological grade (p < 0.01) and elevated in glioblastoma (p < 0.01).
      High expression of CPEB4 was associated with significantly poor prognosis, and
      could be identified as an independent risk factor for overall survival (OS) and
      progression-free survival (PFS) of glioblastoma patients (hazard ratio (HR) =
      1.730, p = 0.014 and HR = 1.877, p = 0.004, respectively). In vitro studies
      further showed that downregulation of CPEB4 significantly reduced the growth rate
      of T98G and U251 cells comparing with the controls. CONCLUSION: Our study
      indicated that increased expression of CPEB4 in primary glioblastoma is a novel
      biomarker for predicting poor outcome of patients and suppression of CPEB4
      inhibit tumor cell proliferation, suggesting a potential therapeutic target for
      glioblastoma.

PMID- 29642045
TI  - Effects of different Ca2+ level on fluoride-induced apoptosis pathway of
      endoplasmic reticulum in the rabbit osteoblast in vitro.
AB  - In reviewing the literature, the cellular mechanism of fluoride F-induced
      osteoblast OB cells apoptosis is diverse and perplexing, but detailed regulatory
      pathway, targets and role of extracellular Ca2+ remains still unclear. Hence, in
      the present study, we investigated the effects of F (9 mg/L F ion) and different
      Ca2+ (0.5, 1, 2, 4, 8 mmol/L) levels treatment on the proliferation rate of
      osteoblast cells, intracellular free Ca2+ ([Ca2+]i) and endoplasmic reticulum
      (ER) stress apoptosis pathway related gene levels of rabbit OB cells. Our results
      demonstrated that F exposure had a pronounced negative effect on osteoblast
      survival, further different Ca2+ levels treatment suggested that low
      concentration of Ca2+ (0.5-1 mmol/L) relieved the damaged effect, on the
      contrary, high concentration of Ca2+ (2-8 mmol/L) enhanced the effect. In
      addition, F significantly increased [Ca2+]i levels and the expression of ER
      stress-induced cell apoptosis pathway related genes. Treatment with 0.5-1 mmol/L
      Ca2+ markedly reversed the F-induced harmful effects, but high dose Ca2+ (2-8
      mmol/L) enhanced these effects. In summary, 0.5-1 mmol/L Ca2+ can alleviate F
      induced OB cells injure through ER stress apoptosis pathway, which provided a
      dose basis for the future study on the treatment of skeletal fluorosis with Ca2+.

PMID- 29642044
TI  - High-speed 3D imaging of cellular activity in the brain using axially-extended
      beams and light sheets.
AB  - As optical reporters and modulators of cellular activity have become increasingly
      sophisticated, the amount that can be learned about the brain via high-speed
      cellular imaging has increased dramatically. However, despite fervent innovation,
      point-scanning microscopy is facing a fundamental limit in achievable 3D imaging
      speeds and fields of view. A range of alternative approaches are emerging, some
      of which are moving away from point-scanning to use axially-extended beams or
      sheets of light, for example swept confocally aligned planar excitation (SCAPE)
      microscopy. These methods are proving effective for high-speed volumetric imaging
      of the nervous system of small organisms such as Drosophila (fruit fly) and D.
      Rerio (Zebrafish), and are showing promise for imaging activity in the living
      mammalian brain using both single and two-photon excitation. This article
      describes these approaches and presents a simple model that demonstrates key
      advantages of axially-extended illumination over point-scanning strategies for
      high-speed volumetric imaging, including longer integration times per voxel,
      improved photon efficiency and reduced photodamage.

PMID- 29642046
TI  - DNA-functionalized gold nanoparticle-based fluorescence polarization for the
      sensitive detection of silver ions.
AB  - Despite their practical applications, Ag+ ions are environmental pollutants and
      affect human health. So the effective detection methods of Ag+ ions are
      imperative. Herein, we developed a simple, sensitive, selective, and cost
      effective fluorescence polarization sensor for Ag+ detection in aqueous solution
      using thiol-DNA-functionalized gold nanoparticles (AuNPs). In this sensing
      strategy, Ag+ ions can specifically interact with a cytosine-cytosine (CC)
      mismatch in DNA duplexes and form stable metal-mediated cytosine-Ag+-cytosine (C
      Ag+-C) base pairs. The formation of the C-Ag+-C complex results in evident
      changes in the molecular volume and fluorescence polarization signal. To achieve
      our aims, we prepared two complementary DNA strands containing C-base mismatches
      (probe A: 5'-SH-A10-TACCACTCCTCAC-3' and probe B: 5'-TCCTCACCAGTCCTA-FAM-3'). The
      stable hybridization between probe A and probe B occurs with the formation of the
      C-Ag+-C complex in the presence of Ag+ ions, leading to obvious fluorescence
      quenching in comparison to the system without AuNP enhancement. The assay can be
      used to identify nanomolar levels of Ag+ within 6 min at room temperature, and
      has extremely high specificity for Ag+, even in the presence of higher
      concentrations of interfering metal ions. Furthermore, the sensor was
      successfully applied to the detection of Ag+ ions in environmental water samples
      and showed excellent selectivity and high sensitivity, implying its promising
      application in the future.

PMID- 29642047
TI  - Physico-chemical and microbial perturbations of Andalusian pine forest soils
      following a wildfire.
AB  - Wildfires are a recurrent disturbance in Mediterranean forests, triggered by high
      fuel load, high environmental temperature and low humidity. Although, human
      intervention is behind the initiation of most fire episodes, the situation is
      likely to worsen in the future due to the effects of climate change in the
      Mediterranean "hot-spot". Here we study chemical, physical and microbial
      characteristics of burnt soils from two well differentiated sites at Sierra de
      Cazorla, Segura and Las Villas Natural Park, Andalusia, (Spain) affected and
      unaffected by a wildfire, and followed their evolution for three years. The soils
      affected by a severe surface burn showed a significant increase in organic matter
      after 3years from the fire. Viable bacteria and fungi also increased, especially
      2-3years post-burning. Substrate induced respiration (SIR) also increased
      significantly in burnt soil from site 1 (rendzina on carbonate) while a
      significant decrease was observed in the burnt soils sampled from site 2 (calcic
      luvisols) in samples taken one month after the wildfire. A recovery in both SIR
      and organic matter was observed after 2 and 3years. Of seven soil enzymes
      studied, only phosphatase activity was significantly higher in most burnt soils
      over the three years. Analysis of bacterial community diversity using clone
      libraries showed a recovery in the number of phyla in burnt soils after 2 and
      3years in both sites, with an increase in Proteobacteria and Firmicutes and a
      decrease in Acidobacteria phyla. For Bacteroidetes, the percentages were lower in
      most burnt samples. This study reveals that if wildfire increases the organic
      matter availability, then the microbial community responds with increased
      activity and biomass production. Although fire exerts an initial impact on the
      soil bacterial community, its structure and functional profile soon recovers
      (after 2-3years) contributing to soil recovery.

PMID- 29642048
TI  - Road traffic air and noise pollution exposure assessment - A review of tools and
      techniques.
AB  - Road traffic induces air and noise pollution in urban environments having
      negative impacts on human health. Thus, estimating exposure to road traffic air
      and noise pollution (hereafter, air and noise pollution) is important in order to
      improve the understanding of human health outcomes in epidemiological studies.
      The aims of this review are (i) to summarize current practices of modelling and
      exposure assessment techniques for road traffic air and noise pollution (ii) to
      highlight the potential of existing tools and techniques for their combined
      exposure assessment for air and noise together with associated challenges,
      research gaps and priorities. The study reviews literature about air and noise
      pollution from urban road traffic, including other relevant characteristics such
      as the employed dispersion models, Geographic Information System (GIS)-based
      tool, spatial scale of exposure assessment, study location, sample size, type of
      traffic data and building geometry information. Deterministic modelling is the
      most frequently used assessment technique for both air and noise pollution of
      short-term and long-term exposure. We observed a larger variety among air
      pollution models as compared to the applied noise models. Correlations between
      air and noise pollution vary significantly (0.05-0.74) and are affected by
      several parameters such as traffic attributes, building attributes and
      meteorology etc. Buildings act as screens for the dispersion of pollution, but
      the reduction effect is much larger for noise than for air pollution. While,
      meteorology has a greater influence on air pollution levels as compared to noise,
      although also important for noise pollution. There is a significant potential for
      developing a standard tool to assess combined exposure of traffic related air and
      noise pollution to facilitate health related studies. GIS, due to its geographic
      nature, is well established and has a significant capability to simultaneously
      address both exposures.

PMID- 29642049
TI  - Transformation of methylparaben during water chlorination: Effects of bromide and
      dissolved organic matter on reaction kinetics and transformation pathways.
AB  - The reaction kinetics, products, and pathways of methylparaben (MeP) during water
      chlorination with and without bromide (Br-) were investigated to better
      understand the fate of parabens in chlorinated waters. During the chlorination of
      MeP-spiked waters without Br-, MeP was transformed into mono-Cl-MeP and di-Cl-MeP
      with apparent second-order rate constants (kapp) of 64M-1s-1 and 243M-1s-1 at
      pH7, respectively, while further chlorination of di-Cl-MeP was relatively slower
      (kapp=1.3M-1s-1 at pH7). With increasing Br- concentration, brominated MePs, such
      as mono-Br-MeP, Br-Cl-MeP, and di-Br-MeP, became major transformation products.
      The di-halogenated MePs (di-Cl-MeP, Br,Cl-MeP, and di-Br-MeP) showed relatively
      low reactivity to chlorine at pH7 (kapp=1.3-4.6M-1s-1) and bromine (kapp=32-71M
      1s-1), which explains the observed high stability of di-halogenated MePs in
      chlorinated waters. With increasing pH from 7 to 8.5, the transformation of di
      halogenated MePs was further slowed due to the decreasing reactivity of di-MePs
      to chlorine. The formation of the di-halogenated MePs and their further
      transformation become considerably faster at Br- concentrations higher than
      0.5MUM (40MUg/L). Nonetheless, the accelerating effect of Br- diminishes in the
      presence of dissolved organic matter (DOM) extract (Suwannee River humic acid
      (SRHA)) due to a more rapid consumption of bromine by DOM than chlorine. The
      effect of Br- on the fate of MeP was less in the tested real water matrices,
      possibly due to a more rapid bromine consumption by the real water DOM compared
      to SRHA. A kinetic model was developed based on the determined species-specific
      second-order rate constants for chlorination/bromination of MeP and its
      chlorinated and brominated MePs and the transformation pathway information, which
      could reasonably simulate the transformation of MePs during the chlorination of
      water in the presence of Br- and selected DOM.

PMID- 29642050
TI  - Metals in geopropolis from beehive of Melipona scutellaris in urban environments.
AB  - Geopropolis, a different type of propolis, presents a mixture of resin and
      exudates, containing wax, silt, and sand particles. This product has been the
      subject of research interest for its physicochemical properties, economic
      importance, and likely for environmental monitoring. The determination of toxic
      metals in hive products has been reported as an efficient tool for environmental
      monitoring. As the honey production is now common in urban environments, this
      study aimed to determine the concentration of toxic metals in the Melipona
      scutellaris geopropolis of the Metropolitan Region of Salvador, Bahia.
      Geopropolis and soil samples were collected from seven important beehives between
      June 2015 and July 2016. After EPA 3050B acid digestion procedure, metals were
      determined by ICP OES. As the geopropolis is partially made from soil, the values
      of Cr and Fe were extremely more important than the values reported in propolis,
      wax, and honey found in other worldwide studies. It gives different
      characteristics to this product depending on the location of the hive and
      characterizes it as an efficient integrating indicator of soil pollution. Using
      the enrichment factor, we determined that the soils around the meliponary are not
      or only slightly polluted by Cu, Cr, Ni, Pb and Zn. However, there was a shift in
      the particle size of geopropolis, being loamier and less sandy than the
      surrounding soil. In such case, a higher metal content could be expected, though
      no metal enrichment in the geopropolis was found, even a decrease in zinc,
      possibly due to the exclusion of metals by bees, was noted. Nevertheless, the
      results on the proportions of lithogenic metal and anthropogenic metal indicate
      that some metals have an external origin (about 20% for Ni and Cu). Geopropolis
      can be considered as a good environmental indicator even in low contaminated
      areas.

PMID- 29642052
TI  - Self-resistance mechanisms to DNA-damaging antitumor antibiotics in
      actinobacteria.
AB  - Streptomyces and few other Actinobacteria naturally produce compounds currently
      used in chemotherapy for being cytotoxic against various types of tumor cells by
      damaging the DNA structure and/or inhibiting DNA functions. DNA-damaging
      antitumor antibiotics belong to different classes of natural compounds that are
      structurally unrelated such as anthracyclines, bleomycins, enediynes, mitomycins,
      and prodiginines. By targeting a ubiquitous molecule and housekeeping functions,
      these compounds are also cytotoxic to their producer. How DNA-damaging antitumor
      antibiotics producing actinobacteria avoid suicide is the theme of the current
      review which illustrates the different strategies developed for self-resistance
      such as toxin sequestration, efflux, modification, destruction, target
      repair/protection, or stochastic activity. Finally, the observed spatio-temporal
      correlation between cell death, morphogenesis, and prodiginine production in S.
      coelicolor suggests a new physiological role for these molecules, that, together
      with their self-resistance mechanisms, would function as new types of toxin
      antitoxin systems recruited in programmed cell death processes of the producer.

PMID- 29642051
TI  - Transcriptome sequencing dissection of the mechanisms underlying differential
      cold sensitivity in young and mature leaves of the tea plant (Camellia sinensis).
AB  - The tea plant originated in tropical and subtropical regions and experiences
      considerable challenges during cold winters and late spring frosts. After short
      term chilling stress, young leaves of tea plants exhibit browning, a significant
      increase in electrolyte leakage and a marked decrease in the maximal
      photochemical efficiency of photosystem II (Fv/Fm) compared with mature leaves.
      To identify the mechanisms underlying the different chilling tolerance between
      young and mature leaves of the tea plant, we used Illumina RNA-Seq technology to
      analyse the transcript expression profiles of young and mature leaves exposed to
      temperatures of 20  degrees C, 4  degrees C, and 0  degrees C for 4 h. A total of
      45.70-72.93 million RNA-Seq raw reads were obtained and then de novo assembled
      into 228,864 unigenes with an average length of 601 bp and an N50 of 867 bp. In
      addition, the differentially expressed unigenes were identified via Venn diagram
      analyses for paired comparisons of young and mature leaves. Functional
      classifications based on Gene Ontology and Kyoto Encyclopedia of Genes and
      Genomes enrichment analyses revealed that the up-regulated differentially
      expressed genes were predominantly related to the cellular component terms of
      chloroplasts and cell membranes, the biological process term of oxidation
      reduction process as well as the pathway terms of glutathione metabolism and
      photosynthesis, suggesting that these components and pathways may contribute to
      the cold hardiness of mature leaves. Conversely, the inhibited expression of
      genes related to cell membranes, carotenoid metabolism, photosynthesis, and ROS
      detoxification in young leaves under cold conditions might lead to the
      disintegration of cell membranes and oxidative damage to the photosynthetic
      apparatus. Further quantitative real-time PCR testing validated the reliability
      of our RNA-Seq results. This work provides valuable information for understanding
      the mechanisms underlying the cold susceptibility of young tea plant leaves and
      for breeding tea cultivars with superior frost resistance via the genetic
      manipulation of antioxidant enzymes.

PMID- 29642053
TI  - Current status of Severe Fever with Thrombocytopenia Syndrome vaccine
      development.
AB  - Severe Fever with Thrombocytopenia Syndrome (SFTS) is a new emerging tick-borne
      disease caused by the phlebovirus, SFTS virus (SFTSV). The virus was discovered
      in central China in 2009 and has since been identified in both Japan and South
      Korea. Significant progress has been made on the molecular biology of the virus,
      and this has been used to develop diagnostic assays and reagents. Less progress
      has been made on the epidemiology, maintenance and transmission, clinical
      manifestations, immunological responses, and treatment regimens. A number of
      animal models have been investigated but, to date, none recapitulate all the
      clinical manifestations seen in humans. Vaccine development is at an early
      discovery phase.

PMID- 29642054
TI  - Supplementing research ethics training in psychiatry residents: A five-tier
      approach.
AB  - BACKGROUND: Ethics training is a key step in the research supervision of
      psychiatry trainees and there is need for a structured educational module.
      METHODS: We developed a new research ethics training module for psychiatry
      residents - The Five-Tier Approach. Twenty-five first year psychiatry residents
      of an academic psychiatric training centre in India participated in this multi
      session workshop. Module 1 included the completion of NIH online certification
      course for research ethics training. Module 2 was a one-hour interactive group
      discussion on ethical principles in research. Module 3 was a two-hour session
      consisting of case-based group discussion of nine selected research vignettes.
      Module 4 involved preparation of an informed consent form. Module 5 was a mock
      ethics committee role-played by seven students while the larger group observed
      using a Fish Bowl technique and provided feedback. Assessments were done during
      the third and final modules. RESULTS: During the third module, understanding
      regarding certain areas - autonomy, benefits and justice was found to be
      inadequate. In the final step, all ethical aspects were covered by the students.
      DISCUSSION: This five-tier approach seems like a superior tool for research
      ethics training in academic institutions, especially in Southeast Asia, where the
      student-teacher ratios are generally very high.

PMID- 29642055
TI  - Increased Group 2 Innate Lymphoid Cells Are Correlated with Eosinophilic
      Granulocytes in Patients with Allergic Airway Inflammation.
AB  - The T helper 2 (Th2)-type response was considered the hypostasis of allergic
      airway diseases, including asthma and allergic rhinitis (AR). However, more
      recent studies have suggested that allergic airway inflammation also depends on
      innate immunity and is closely related to group 2 innate lymphoid cells (ILC2s).
      This study evaluated the ILC2 levels of asthma subjects, patients with asthma and
      AR, and healthy individuals, regarding how to investigate the relationship
      between clinical data and ILC2 levels. It was found that asthma patients and
      asthma with AR patients had higher ILC2 levels compared to healthy subjects.
      ILC2s were positively correlated with the percentage of eosinophils in patients
      with asthma and AR, but not with pulmonary function. ILC2 levels were higher in
      mild asthma subjects than in patients with severe asthma. This study provides a
      new interpretation of the pathogenesis of allergic airway inflammation and may
      provide a new direction for the diagnosis and assessment of allergic airway
      diseases.

PMID- 29642056
TI  - Optimizing the Use of a Voided Urine Cytology Specimen as Control Material for
      Anti-BK Virus Immunohistochemical Staining.

PMID- 29642057
TI  - In utero Fetal Intubation for a Large Neck Mass: A Minimally Invasive EXIT
      Option.
AB  - Fetuses with obstructive neck and orofacial lesions have been delivered via an ex
      utero intrapartum treatment (EXIT) procedure to facilitate securement of the
      airway while on placental circulation. Pregnancy-related cardiovascular changes
      and technical issues unique to an EXIT procedure increase fetal and maternal
      risks relative to a standard cesarean section. In order to circumvent such
      issues, fetal endoscopic intubation has been proposed. We report a case of a
      fetus with a large neck mass (mixed solid and multiloculated cystic lesion
      measuring 9.2 * 5.3 * 8.5 cm, neck hyperextension, protruding tongue, and serial
      gagging movements) that was successfully intubated in utero and delivered at 36
      weeks and 0 days via standard cesarean section, thereby avoiding an EXIT
      procedure. The risks, benefits, and technical issues of in utero tracheal
      intubation are reviewed.

PMID- 29642058
TI  - Cytological Findings of Malignant and Benign Head and Neck Masses in Somalia.
AB  - OBJECTIVE: There are no up-to-date records on head and neck masses (HNMs) in
      Somalia. This cytological study is the first to demonstrate the benefits and
      findings of fine-needle aspiration cytology in evaluating HNMs in the adult
      population of Somalia. STUDY DESIGN: A total of 116 aspiration samples were taken
      from different levels of the neck region, except for the thyroid. Cases were
      classified as salivary gland, lymph node, or soft tissue/cystic lesions. They
      were classified according to age, gender, and cytological diagnosis. RESULTS:
      Patients included 54 (46.6%) males and 62 (53.4%) females, with a mean age of
      40.6 years. Seventy-two patients (62.1%) had benign lesions, while 44 (37.9%) had
      malignant lesions. Necrotizing granulomatous lymphadenitis (n = 51, 70.8% of the
      benign findings) and lymph node metastasis of squamous cell carcinoma (n = 13,
      29.5% of the malignant findings) were the most frequent findings. CONCLUSION:
      Fine-needle aspiration is a useful procedure in the diagnosis of neck masses. It
      is a cheap and easy guiding method for diagnosing granulomatous lymphadenitis and
      advanced-stage metastatic cancers, which are common in this country.

PMID- 29642059
TI  - Experiences Of Individuals Concerning Combined Orthodontic and Orthognathic
      Surgical Treatment: A Qualitative Twitter Analysis.
AB  - OBJECTIVE: The aim of this qualitative study was to analyze the content of posts
      on Twitter in order to gain an in-depth understanding of patients' thoughts and
      experiences surrounding orthognathic surgical treatment. MATERIALS AND METHODS:
      Using the Twitter search function, with the keywords "jaw surgery," the 1,000
      most recent posts on Twitter with relevance to a combined orthodontic and
      orthognathic surgical treatment were extracted. After applying relevant inclusion
      and exclusion criteria, the selected posts were analyzed using thematic analysis
      by 2 independent investigators. Distinct themes and subthemes were developed.
      RESULTS: A total of 689 posts were analyzed; the 3 main themes identified in
      relation to orthognathic surgery were preoperative engagement, postoperative
      difficulties, and posttreatment satisfaction. Twelve subthemes were also
      identified, expressing issues such as anticipation or apprehension of the
      surgical procedure, postoperative pain and edema, dietary restrictions and weight
      loss, paresthesia, depression, and satisfaction with improvements in appearance
      and self-confidence. The 6 terms most frequently used in tweets were "recovery,"
      "braces," "swollen," "eat," "liquid diet," and "pain." CONCLUSIONS: The findings
      from the present study can increase the awareness of clinicians involved in the
      combined orthodontic and orthognathic surgical treatment of patients with
      dentofacial deformities, allowing them to better educate and counsel their
      patients throughout the entire treatment process.

PMID- 29642061
TI  - Higher Incidence Rates of Hypothyroidism and Late TSH Rise in Preterm Very-Low
      Birth-Weight Infants at a Tertiary Care Center.
AB  - BACKGROUND/AIMS: Preterm newborns with a very low birth weight (VLBW) of < 1,500
      g have an atypical form of hypothyroidism with a delayed rise in TSH,
      necessitating a second newborn screening specimen collection. The aims of this
      study were to survey the compliance with second newborn screening to detect
      delayed TSH rise in VLBW preterm infants at a tertiary care center, and to
      determine the rate of atypical hypothyroidism. METHODS: Retrospective review of
      the records of 104 preterm VLBW infants. Late TSH rise was defined as an increase
      in TSH concentration after 14 days of age in the presence of a normal initial
      screen. RESULTS: The compliance rate was 92% for the second screening. High rates
      of hypothyroidism (16.3%) and of late TSH rise (4.8%) were detected. Patients
      with hypothyroidism had a significantly lower birth weight (p = 0.01) and longer
      hospital stay (p = 0.004). Patients with late versus those with early TSH rise
      had a significantly lower mean birth weight (851 +/- 302 vs. 1,191 +/- 121 g, p =
      0.004). CONCLUSION: The rates of early and late TSH rise in this VLBW population
      were higher than those in the literature and could be due to the use of povidone
      iodine disinfectants. The yield of a second TSH screening in this study was high
      indicating the need for vigilance in screening VLBW preterm infants.

PMID- 29642060
TI  - Metabolic Syndrome Severity and Risk of CKD and Worsened GFR: The Jackson Heart
      Study.
AB  - BACKGROUND/AIMS: The metabolic syndrome (MetS), as assessed using dichotomous
      criteria, is associated with increased risk of future chronic kidney disease
      (CKD), though this relationship is unclear among African Americans, who have
      lower risk for MetS but higher risk for CKD. METHODS: We performed logistic
      regression using a sex- and race-specific MetS-severity z-score to assess risk of
      incident CKD among 2,627 African-American participants of the Jackson Heart
      Study, assessed at baseline and 8 years later. Based on quartile of baseline MetS
      severity, we further assessed prevalence of being in the lowest quartile of
      baseline GFR, the lowest quartile of relative GFR at follow-up, microalbuminuria
      and incident CKD. RESULTS: Higher MetS-severity was associated with higher
      prevalence of GFR in the lowest quartile at baseline among males and females.
      Among African-American females but not males, higher baseline MetS-severity was
      associated with a higher prevalence of baseline elevations in microabuminuria
      (p<0.01), steep decline in GFR (p<0.001) and a higher incidence of CKD
      (p<0.0001). Women in increasing quartiles of baseline MetS-severity exhibited a
      linear trend toward higher odds of future CKD (p<0.05), with those in the 4th
      quartile of MetS-severity (compared to the 1st) having an odds ratio of 2.47 (95%
      confidence interval 1.13, 5.37); no such relationship was seen among men (p value
      for trend 0.49). CONCLUSION: MetS-severity exhibited sex-based interactions
      regarding risk for future GFR deterioration and CKD, with increasing risk in
      women but not men. These data may have implications for triggering CKD screening
      among African-American women with higher degrees of MetS-severity.

PMID- 29642063
TI  - Therapy for Immunoglobulin D Plasma Cell Myeloma.

PMID- 29642062
TI  - Dexamethasone Intravitreal Implant for Early Treatment and Retreatment of Macular
      Edema Related to Branch Retinal Vein Occlusion: The Multicenter COBALT Study.
AB  - PURPOSE: To evaluate the effect of dexamethasone intravitreal implant for macular
      edema (ME) following branch retinal vein occlusion (BRVO) in Korean patients.
      METHODS: We performed a prospective, open-label, multicenter study of 71 patients
      with ME for < 3 months. Retreatment was allowed >=4 months from the last
      injection. RESULTS: At 6 and 12 months, mean +/- SD best-corrected visual acuity
      (BCVA) improvement was 18.6 +/- 12.9 and 15.3 +/- 15.0 letters, respectively.
      Approximately 70% of maximum treatment response was observed after 1 week. Over
      the 12-month period, 32 and 49% of patients received 1 and 3 injections,
      respectively, with a mean +/- SD interval of 20.0 +/- 5.0 weeks. Patients who
      required 3 injections had higher central retinal thickness (CRT) and larger
      macular nonperfusion at baseline compared to those requiring only 1 injection.
      Adverse events included increased intraocular pressure (35%) and newly diagnosed
      cataract (16%). CONCLUSIONS: Intravitreal dexamethasone treatment with an
      interval of >=4 months provides rapid and significantly better improvement in
      BCVA and CRT in patients with BRVO-associated ME.

PMID- 29642064
TI  - Integrative Bioinformatics Analysis Provides Insight into the Molecular
      Mechanisms of Chronic Kidney Disease.
AB  - BACKGROUND/AIMS: Chronic kidney disease (CKD) is a worldwide public health
      problem. Regardless of the underlying primary disease, CKD tends to progress to
      end-stage kidney disease, resulting in unsatisfactory and costly treatment. Its
      common pathogenesis, however, remains unclear. The aim of this study was to
      provide an unbiased catalog of common gene-expression changes of CKD and reveal
      the underlying molecular mechanism using an integrative bioinformatics approach.
      METHODS: We systematically collected over 250 Affymetrix microarray datasets from
      the glomerular and tubulointerstitial compartments of healthy renal tissues and
      those with various types of established CKD (diabetic kidney disease,
      hypertensive nephropathy, and glomerular nephropathy). Then, using stringent
      bioinformatics analysis, shared differentially expressed genes (DEGs) of CKD were
      obtained. These shared DEGs were further analyzed by the gene ontology (GO) and
      pathway enrichment analysis. Finally, the protein-protein interaction
      networks(PINs) were constructed to further refine our results. RESULTS: Our
      analysis identified 176 and 50 shared DEGs in diseased glomeruli and tubules,
      respectively, including many transcripts that have not been previously reported
      to be involved in kidney disease. Enrichment analysis also showed that the
      glomerular and tubulointerstitial compartments underwent a wide range of unique
      pathological changes during chronic injury. As revealed by the GO enrichment
      analysis, shared DEGs in glomeruli were significantly enriched in exosomes. By
      constructing PINs, we identified several hub genes (e.g. OAS1, JUN, and FOS) and
      clusters that might play key roles in regulating the development of CKD.
      CONCLUSION: Our study not only further reveals the unifying molecular mechanism
      of CKD pathogenesis but also provides a valuable resource of potential biomarkers
      and therapeutic targets.

PMID- 29642065
TI  - A Pathogenetic Classification of Diabetic Macular Edema.
AB  - PURPOSE: The aim of this study was to define a new pathogenetic classification of
      diabetic macular edema (DME) and to present the results of its application in
      common clinical practice. METHODS: One hundred and seventy-seven consecutive
      patients with center-involving DME, central retinal thickness (CRT) >=250 um,
      were prospectively enrolled. A complete ophthalmological examination included
      best-corrected visual acuity (BCVA) assessment, fundus photography, and spectral
      domain optical coherence tomography (OCT). The DME classification was broken down
      into 4 categories, combining the presence of retinal thickening with the
      presence/absence of visible vascular dilations and OCT-detectable macular
      traction. The OCT parameters included were as follows: CRT, subretinal fluid,
      intraretinal cysts, and hyper- reflective foci (HF). RESULTS: Four subtypes of
      DME were identified: vasogenic (131 eyes, DME with vascular dilation),
      nonvasogenic (46 eyes, DME without vascular dilation), tractional (11 eyes), and
      mixed DME (13 eyes). Vasogenic DME was the pattern mainly represented in each
      subclass of CRT (< 300, 300-400, and > 400 um), with tractional DME observed
      especially with CRT > 400 um. Internal and external cysts and a greater presence
      of hard exudates were predominantly found in vasogenic DME, whereas HF was
      equally distributed in the 4 DME subgroups. CONCLUSION: The study offers a new
      pathogenetic classification able to detect significant differences among DME
      subtypes. A tailored therapeutic approach could take into consideration specific
      changes associated with the different DME subtypes.

PMID- 29642066
TI  - Neutrophils and Bacterial Immune Evasion.
AB  - Neutrophils are an important component of the innate immune system and provide a
      front line of defense against bacterial infection. Although most bacteria are
      killed readily by neutrophils, some bacterial pathogens have the capacity to
      circumvent destruction by these host leukocytes. The ability of bacterial
      pathogens to avoid killing by neutrophils often involves multiple attributes or
      characteristics, including the production of virulence molecules. These molecules
      are diverse in composition and function, and collectively have the potential to
      alter or inhibit neutrophil recruitment, phagocytosis, bactericidal activity,
      and/or apoptosis. Here, we review the ability of bacteria to target these
      processes.

PMID- 29642067
TI  - omega-3 Polyunsaturated Fatty Acid Postconditioning Protects the Isolated
      Perfused Rat Heart from Ischemia-Reperfusion Injury.
AB  - AIMS: This study aimed to evaluate the cardioprotective effects of omega-3
      polyunsaturated fatty acids (PUFAs) postconditioning against ischemia-reperfusion
      (I/R) injury. METHODS: Sixty Sprague-Dawley rats were randomly divided into 4
      groups (n = 15 for each) and used to generate the Langendorff isolated perfused
      rat heart model. The sham group received a continuous perfusion of 150 min. The
      remaining three I/R-treated groups sequentially received a 30-min perfusion, a 30
      min cardioplegia, and a 90-min reperfusion. The I/R-ischemic preconditioning (IP)
      group additionally received three cycles of 20-s reperfusion and 20-s coronary
      reocclusion preceded the 90 min of reperfusion. The I/R-omega group were perfused
      with omega-3 PUFAs for 15 min before the 90 min of reperfusion. The myocardial
      infarct size, the degree of mitochondrial damage, the antioxidant capacity of the
      myocardium, and the cardiac functions during reperfusion were compared among
      groups. RESULTS: Compared with the I/R group, the I/R-omega group had
      significantly reduced myocardial infarct size, reduced levels of lactate
      dehydrogenase and malondialdehyde, elevated superoxide dismutase level, and
      elevated rising (+dp/dtmax) and descending (-dp/dtmax) rate of left ventricular
      pressure. The I/R-omega group had a significantly lower rate of mitochondrial
      damage in myocardial tissue compared with the I/R and I/R-IP groups. CONCLUSION:
      omega-3 PUFA postconditioning possesses good cardioprotective effects and may be
      developed into a therapeutic strategy for myocardial I/R injury.

PMID- 29642068
TI  - Angiopoietin-2, Renal Deterioration, Major Adverse Cardiovascular Events and All
      Cause Mortality in Patients with Diabetic Nephropathy.
AB  - BACKGROUND/AIMS: Diabetic nephropathy is the leading cause of end-stage renal
      disease and accounts for 30~40% of patients requiring maintenance dialysis,
      thereby increasing the burden on health insurance programs. Diabetic nephropathy
      is also the strongest predictor of cardiovascular morbidity and mortality. The
      aim of this study was to examine whether angiopoietin-2 (Angpt2), a modulator of
      endothelial function, affects the clinical outcomes of diabetic patients.
      METHODS: This study enrolled 236 patients with diabetes mellitus with estimated
      glomerular filtration rate (eGFR) < 60ml/min/1.73m2 from January 2006 to December
      2011, who were followed until June 2017. Clinical outcomes included renal
      outcomes (commencing dialysis and rapid decline in renal function (eGFR decline >
      3 ml/min per 1.73 m2/year)), major adverse cardiovascular events (MACEs), and all
      cause mortality. RESULTS: Over a mean follow-up period of 3.9+/-2.7 years, 135
      (57.2%) patients commenced dialysis, 106 (44.9%) had rapid decline in renal
      function, and 50 (21.2%) had MACEs or died from all-causes. Log-formed Angpt2 was
      significantly associated with increased risks of commencing dialysis (HR: 3.91,
      95% CI: 1.56-9.76), rapid renal function decline (OR: 6.81, 95% CI: 1.06-43.88),
      and MACEs or all-cause mortality (HR: 6.34, 95% CI: 1.18-33.97) in the adjusted
      analysis. Patients in the highest quartile had hazard ratios of 2.90 and 3.11 for
      commencing dialysis and rapid renal function decline, respectively, compared to
      those in the lowest quartile after adjustments. Similar significant dose-response
      results were found in composite outcomes of either MACEs or all-cause mortality.
      CONCLUSION: Angpt2 is an independent predictor of adverse clinical outcomes in
      diabetic patients. Further studies are needed to identify the pathogenic role of
      Angpt2 in renal deterioration and cardiovascular complications of diabetes
      mellitus.

PMID- 29642070
TI  - Personality Disorders, Functioning and Health.

PMID- 29642069
TI  - If It's Not Broken, Should We Fix It? Ventriculoperitoneal Shunt Catheter
      Contributing to Closed-Loop Small Bowel Obstruction in a Pediatric Patient with
      Ileostomy.

PMID- 29642071
TI  - Risk Factor Profiles Achieved with Medical Therapy in Prevalent Patients with
      Pulmonary Arterial and Distal Chronic Thromboembolic Pulmonary Hypertension.
AB  - BACKGROUND: The latest pulmonary hypertension (PH) guidelines define therapeutic
      goals in terms of symptoms, exercise capacity, and haemodynamics for patients
      with pulmonary arterial hypertension (PAH) and recommend advanced combined
      medical therapy. For inoperable or post-surgical residual distal chronic
      thromboembolic PH (CTEPH) medical treatment is similarly advised. OBJECTIVES: We
      analysed whether risk factor goals are achieved and combination therapy is used
      in prevalent patients with PAH or distal CTEPH. METHODS: PAH or distal CTEPH
      patients who were seen at the University Hospital Zurich during the last year
      were analysed in terms of demography, clinical data, medication, and therapeutic
      goals. Achievement of therapeutic goals was defined as New York Heart Association
      (NYHA) class <=II, N-terminal pro-brain natriuretic peptide (NTpro-BNP) < 300
      ng/L, and 6-min walking distance (6MWD) > 440 m. RESULTS: A total of 108 PAH
      patients (age 59 +/- 18 years, 62% female, 64% idiopathic, 36% associated) and 38
      distal CTEPH patients (age 69 +/- 14 years, 55% female) were included. They had
      been diagnosed on average 66 +/- 48 months (+/-SD) previously. The percentage of
      PAH/CTEPH patients with NYHA <=II was 52/53, respectfully, the percentage of
      those with NTproBNP < 300 ng/L was 61/52, and with 6MWD > 440 m 63/50. Overall,
      33/31% fulfilled 3 and 29/35% fulfilled 2 of these goals. Regarding therapy, 43%
      of PAH patients were on double and 10% on triple combination therapy, whereas 16%
      of distal CTEPH patients were on double and 3% on triple combination therapy.
      CONCLUSIONS: In this real-life cohort of prevalent patients with PAH or distal
      CTEPH, targeted drug therapy resulted in an achievement of >=2/3 predefined
      therapeutic goals in 2/3 of patients. Patients with PAH were more likely to
      receive combination therapy compared to CTEPH patients.

PMID- 29642072
TI  - Clinical Relevance of Intra-Tumour Heterogeneity.

PMID- 29642073
TI  - Brain Stimulation Studies of Social Norm Compliance: Implications for Personality
      Disorders?
AB  - Several personality disorders involve pathological behaviors that violate social
      norms, commonly held expectations about what ought to be done in specific
      situations. These symptoms usually emerge early in development, are persistent
      and hard to treat, and are often ego-syntonic. Here I present some recent brain
      stimulation studies suggesting that pathological changes in different aspects of
      norm-compliant behavior reflect dysfunctions of brain circuits involving distinct
      prefrontal brain areas. One set of studies shows that transcranial direct current
      stimulation of the right lateral prefrontal cortex changes the behavioral
      sensitivity to social incentives for norm-compliant behavior. Crucially, social
      norm compliance in response to such incentives could even be increased during
      excitatory stimulation, demonstrating that the affected neural process is a
      biological prerequisite for appropriate reaction to social signals that trigger
      norm compliance. In another set of studies, we show that stimulation of a
      different (more dorsal) part of the right prefrontal cortex enhances honesty in a
      realistic setting where participants had the opportunity to cheat for real
      monetary gains. Interestingly, these stimulation-induced increases in both
      socially cued or purely voluntary norm compliance were not linked to changes in
      other aspects of decision- making (such as risk or impatience), and they did not
      reflect changes in beliefs about what is appropriate behavior. These results
      suggest that disorders of distinct brain circuits may causally underlie
      egosyntotic changes in norm-compliant behavior. This raises the tantalizing
      possibility that pathologies of norm-compliant behavior may be ameliorated by
      interventions targeting the function of these brain circuits.

PMID- 29642075
TI  - Effectiveness of Topical Sucralfate in the Management of Pressure Ulcer in
      Hospitalized Patients: A Prospective, Randomized, Placebo-Controlled Trial.
AB  - BACKGROUND: The aim of this study was to evaluate the effectiveness of topical
      sucralfate in the management of pressure ulcer (PU) in hospitalized patients.
      METHODS: Forty hospitalized patients with stage II PU were included in this
      prospective, double-blind, randomized, placebo-controlled trial and were randomly
      divided into 2 groups receiving either sucralfate gel or placebo, on a daily
      basis. The patients were visited every day for 14 days, the ulcer was evaluated
      using the Pressure Ulcer Scale for Healing (PUSH) and changes to the measured
      scores over time were used as an indicator of wound healing. RESULTS: There were
      no statistically significant differences in any of the demographic
      characteristics between both groups. Both of the interventions reduced the
      average PUSH score, and at the end of the trial, all but 2 patients were healed.
      One in each group discontinued the trial because of exacerbation of the ulcer. No
      significant between-group difference in the average PUSH score reduction was
      observed (6.36 +/- 2.11 vs. 5.89 +/- 1.41, P = 0.42). Although the average
      healing time was less in the sucralfate group (6.05 +/- 2.17 vs. 7.78 +/- 3.42),
      the difference was not statistically significant (P = 0.07). CONCLUSIONS:
      Sucralfate gel does not improve healing of PU compared with placebo.

PMID- 29642074
TI  - Incremental Validity of Montreal Cognitive Assessment Index Scores in Mild
      Cognitive Impairment and Alzheimer Disease.
AB  - BACKGROUND/AIMS: The aim of this paper was to evaluate the incremental validity
      of the Montreal Cognitive Assessment (MoCA) index scores and the MoCA total score
      in differentiating individuals with normal cognition versus mild cognitive
      impairment (MCI) or Alzheimer disease (AD). METHODS: Effect sizes were calculated
      for Alzheimer's Disease Neuroimaging Initiative research participants with normal
      cognition (n = 295), MCI (n = 471), or AD (n = 150). RESULTS: Effect sizes for
      the total score were large (> 0.80) and exceeded the index scores in
      differentiating those with MCI versus normal cognition, MCI versus AD, and AD
      versus normal cognition. A combined score incorporating the Memory, Executive,
      and Orientation indexes also improved incremental validity for all 3 group
      comparisons. CONCLUSION: Administration of the entire MoCA is more informative
      than the index scores, especially in distinguishing normal cognition versus MCI.
      A combined score has stronger incremental validity than the individual index
      scores.

PMID- 29642076
TI  - Comparison of In-Hospital and Long-term Outcomes of Sublobar Lung Cancer Surgery
      by VATS and Open Techniques.
AB  - OBJECTIVE: Sublobar resection is often used as an alternative surgical approach
      in lung cancer patients who are unlikely to tolerate a full lobe resection. This
      study aims to assess outcomes of video-assisted thoracoscopic surgeries (VATS)
      sublobar resection as a surgical technique. MATERIALS AND METHODS: The SEER
      Medicare database was queried to identify patients with primary lung cancer who
      had VATS or open sublobar resection. Baseline clinical differences between VATS
      and open patients were adjusted for in logistic regression and by propensity
      score matching to investigate surgical outcomes. RESULTS: Patients undergoing
      VATS had a greater number of comorbidities (adjusted odds ratio [ORadj], 0.90;
      95% confidence interval [CI], 0.85-0.96) and were less likely to have later stage
      cancer (ORadj, 0.80; 95% CI, 0.67-0.95), squamous compared with adenocarcinoma
      (ORadj, 0.82; 95% CI, 0.68-0.99), large (>30 mm) tumor size (ORadj, 0.56; 95% CI,
      0.0.41-0.75). VATS patients were less likely to have nodes removed for
      examination during surgery (ORadj, 0.76; 95% CI, 0.64-0.90). After propensity
      matching (n=2148), patients who underwent VATS were less likely to experience in
      hospital complications, blood transfusions, and a prolonged length of hospital
      stay than those who had open surgery. There was no statistically significant
      difference in in-hospital or long-term mortality between patients with VATS and
      open surgery. CONCLUSION: In the most compromised lung cancer patients, VATS
      sublobar resection might be the best option.

PMID- 29642077
TI  - Mortality After Stereotactic Radiosurgery for Brain Metastases and Implications
      for Optimal Utilization: A National Cancer Database Study.
AB  - OBJECTIVES: Brain metastases are associated with cancer progression and poor
      outcomes. The use of stereotactic radiosurgery (SRS) to treat brain metastases
      has been increasing due to its potential to quickly treat metastatic disease
      while avoiding the morbidity associated with surgery or whole brain radiation
      therapy (WBRT). This study seeks to analyze practice patterns of the use of SRS
      for brain metastases, focusing on the endpoint of short-term mortality. MATERIALS
      AND METHODS: This study used the National Cancer Database to observe cancer
      patients diagnosed with a non-Central Nervous System primary from 2010 to 2012
      who presented at diagnosis with metastatic disease to the brain and received
      either WBRT or SRS. The primary endpoint was time to mortality determined by the
      Kaplan-Meier product-limit estimate of the failure function. RESULTS: A total of
      18,604 patients were included in the analysis from first day of treatment (16,219
      patients received WBRT and 2385 received SRS). At 90 days, mortality was 39.3%
      for those who received WBRT and 20.0% for those who received SRS. For patients 70
      and older who received SRS, mortality was 30.2% at 90 days. CONCLUSIONS: Analysis
      of short-term mortality after treatment for brain metastases by using the
      National Cancer Database provides a window into national treatment patterns and
      associated outcomes. Roughly 1 in 5 patients who receive SRS and roughly 1 in 3
      patients 70 and older who receive SRS die within 90 days of treatment. These data
      suggest some degree of overutilization of SRS in some patient populations, most
      notably those patients over the age of 70.

PMID- 29642078
TI  - Quality Improvement Education in Residency Training: A Review.
AB  - Hospitals and healthcare institutions have strong external and internal pressures
      to improve patient safety and healthcare quality. Quality improvement education
      has been mandated for resident physicians by the Accreditation Council for
      Graduate Medical Education. This review describes didactic and experiential
      curricula for residents in quality improvement interventions as well as factors
      that create challenges to implementing such a curriculum and those that foster
      it. Resident attitudes, faculty capacity, institutional resources, and dedicated
      time are critical elements influencing the success of quality improvement
      curricula. Faculty interest in quality improvement could be enhanced by academic
      recognition of their work. Recommendations to facilitate publication of quality
      improvement efforts are described.

PMID- 29642079
TI  - Nuclear Spin Attenuates the Anesthetic Potency of Xenon Isotopes in Mice:
      Implications for the Mechanisms of Anesthesia and Consciousness.
AB  - WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW:
      BACKGROUND:: Xenon is an elemental anesthetic with nine stable isotopes. Nuclear
      spin is a quantum property which may differ among isotopes. Xenon 131 (Xe) has
      nuclear spin of 3/2, xenon 129 (Xe) a nuclear spin of 1/2, and the other seven
      isotopes have no nuclear spin. This study was aimed to explore the effect of
      nuclear spin on xenon anesthetic potency. METHODS: Eighty C57BL/6 male mice (7
      weeks old) were randomly divided into four groups, xenon 132 (Xe), xenon 134
      (Xe), Xe, and Xe groups. Due to xenon's low potency, loss of righting reflex ED50
      for mice to xenon was determined with 0.50% isoflurane. Loss of righting reflex
      ED50 of isoflurane was also measured, and the loss of righting reflex ED50 values
      of the four xenon isotopes were then calculated. The exact polarizabilities of
      the isotopes were calculated. RESULTS: Combined with 0.50% isoflurane, the loss
      of righting reflex ED50 values were 15 +/- 4%, 16 +/- 5%, 22 +/- 5%, and 23 +/-
      7% for Xe, Xe, Xe, and Xe, respectively. For xenon alone, the loss of righting
      reflex ED50 values of Xe, Xe, Xe, and Xe were 70 +/- 4%, 72 +/- 5%, 99 +/- 5%,
      and 105 +/- 7%, respectively. Four isotopes had a same exact polarizability of
      3.60 A. CONCLUSIONS: Xenon isotopes with nuclear spin are less potent than those
      without, and polarizability cannot account for the difference. The lower
      anesthetic potency of Xe may be the result of it participating in conscious
      processing and therefore partially antagonizing its own anesthetic potency.
      Nuclear spin is a quantum property, and our results are consistent with theories
      that implicate quantum mechanisms in consciousness.

PMID- 29642080
TI  - Differentiating Drug-related and State-related Effects of Dexmedetomidine and
      Propofol on the Electroencephalogram.
AB  - BACKGROUND: Differentiating drug-related changes and state-related changes on the
      electroencephalogram during anesthetic-induced unconsciousness has remained a
      challenge. To distinguish these, we designed a rigorous experimental protocol
      with two drugs known to have distinct molecular mechanisms of action. We
      hypothesized that drug- and state-related changes can be separated. METHODS:
      Forty-seven healthy participants were randomized to receive dexmedetomidine (n =
      23) or propofol (n = 24) as target-controlled infusions until loss of
      responsiveness. Then, an attempt was made to arouse the participant to regain
      responsiveness while keeping the drug infusion constant. Finally, the
      concentration was increased 1.5-fold to achieve presumable loss of consciousness.
      We conducted statistical comparisons between the drugs and different states of
      consciousness for spectral bandwidths, and observed how drug-induced
      electroencephalogram patterns reversed upon awakening. Cross-frequency coupling
      was also analyzed between slow-wave phase and alpha power. RESULTS: Eighteen
      (78%) and 10 (42%) subjects were arousable during the constant drug infusion in
      the dexmedetomidine and propofol groups, respectively (P = 0.011 between the
      drugs). Corresponding with deepening anesthetic level, slow-wave power increased,
      and a state-dependent alpha anteriorization was detected with both drugs,
      especially with propofol. The slow-wave and frontal alpha activities were
      momentarily disrupted as the subjects regained responsiveness at awakening.
      Negative phase-amplitude coupling before and during loss of responsiveness
      frontally and positive coupling during the highest drug concentration posteriorly
      were observed in the propofol but not in the dexmedetomidine group. CONCLUSIONS:
      Electroencephalogram effects of dexmedetomidine and propofol are strongly drug-
      and state-dependent. Changes in slow-wave and alpha activity seemed to best
      detect different states of consciousness.

PMID- 29642081
TI  - [68Ga]Ga-Pentixafor PET/MRI for CXCR4 Imaging of Chronic Lymphocytic Leukemia:
      Preliminary Results.
AB  - OBJECTIVES: This prospective proof-of-principle study aimed to determine whether
      [Ga]Ga-Pentixafor uptake, which reflects CXCR4 expression, is higher in the bone
      marrow of chronic lymphocytic leukemia (CLL) than in other oncological diseases
      without bone marrow infiltration and can therefore be used for CLL imaging.
      MATERIALS AND METHODS: Thirteen CLL patients and 20 controls (10 with pancreatic
      adenocarcinoma and 10 with mucosa-associated lymphoid tissue lymphoma) with
      histologically proven cancer underwent [Ga]Ga-Pentixafor positron emission
      tomography/magnetic resonance imaging. Standardized [Ga]Ga-Pentixafor uptake
      values (SUVmax, SUVmean) were measured in the bone marrow of the pelvis, the
      lumbar vertebra L4, and the bony structure with the visually highest tracer
      uptake ("hottest lesion"). Mean apparent diffusion coefficient values were also
      measured in the pelvis. Serum leukocyte count (gram per liter), lymphocyte
      percentage (percent), lactate dehydrogenase (unit per liter), beta2-microglobulin
      (milligram per deciliter), and C-reactive protein (milligram per deciliter) were
      measured. Statistical analyses comprised analysis of variance with Games-Howell
      post hoc tests and Spearman correlation coefficients. RESULTS: SUVmax and SUVmean
      differed significantly between CLL and pancreatic adenocarcinoma in the pelvis (P
      = 0.032 and P = 0.008) and lumbar vertebra L4 (both P < 0.001). SUVmean also
      differed in the pelvis (P = 0.020) and L4 (P = 0.041), and SUVmax in L4 (P =
      0.019), between CLL and mucosa-associated lymphoid tissue lymphoma. Receiver
      operating characteristic-based areas under the curve for separation of CLL from
      the control groups were greatest for the SUVmax of the bony structure with the
      strongest [Ga]Ga-Pentixafor uptake (0.94) and the SUVmax of L4 (0.92). There was
      no significant correlation between [Ga]Ga-Pentixafor uptake and pelvic apparent
      diffusion coefficients or serum parameters. CONCLUSIONS: [Ga]Ga-Pentixafor
      positron emission tomography/magnetic resonance imaging may possibly be useful
      for CXCR4-based CLL imaging.

PMID- 29642082
TI  - Early Recurrence of a Solid Variant of Aneurysmal Bone Cyst in a Young Child
      After Resection: Technique and Literature Review and Two-year Follow-up After
      Corpectomy.
AB  - Aneurysmal bone cysts (ABCs) are considered to be rare benign tumors that may
      affect long bones or the vertebral column. Their incidence varies and is reported
      to be 1.4% of all benign skeletal tumors. The solid-variant aneurysmal bone cyst
      (S-ABC) is even rarer and constitutes 3.5% to 7% of all vertebral ABCs. We report
      the case of an Enneking stage 3 S-ABC in a 5-year-old boy at C7 that showed rapid
      local recurrence after primary excision from posterior and dorsal stabilization
      requiring ventral corpectomy and posterior excision of the right lateral mass and
      right posterolateral fusion. Histologic examination disclosed an S-ABC. To our
      knowledge, this is the first case of S-ABC described in the literature that used
      both anterior and posterior approaches and complete corpectomy. Over a 2-year
      period, the patient showed no radiologic or clinical signs of local recurrence
      with excellent neurologic function. Solid-variant aneurysmal bone cysts are
      difficult to diagnose and treat, and careful clinical and radiologic assessment
      should be done to tailor an appropriate surgical plan to prevent recurrence and
      neurologic sequelae. To the best of our knowledge, there are to date no
      publications that studied the behavior of this subtype.

PMID- 29642083
TI  - Severe Maternal or Near Miss Morbidity: Implications for Public Health
      Surveillance and Clinical Audit.
AB  - This chapter reviews the historical development of indicators to identify severe
      maternal morbidity/maternal near miss (SMM/MNM), and their use for public health
      surveillance, research, and clinical audit. While there has been progress toward
      identifying standard definitions for SMM/MNM within countries, there remain
      inconsistencies in the definition of SMM/MNM indicators and their application
      between countries. Using these indicators to screen for events that then trigger
      a clinical audit may both under identify select SMM/MNM (false negative)and over
      identify select SMM/MNM (false positive). Thus, indicators which support the
      efficient identification of SMM/MNM for the purpose of facility-based clinical
      audits are still needed.

PMID- 29642085
TI  - On the Interpretation of Path-specific Effects in Health Disparities Research.

PMID- 29642084
TI  - Socioeconomic and Tobacco Mediation of Ethnic Inequalities in Mortality over
      Time: Repeated Census-mortality Cohort Studies, 1981 to 2011.
AB  - BACKGROUND: Racial/ethnic inequalities in mortality may be reducible by
      addressing socioeconomic factors and smoking. To our knowledge, this is the first
      study to estimate trends over multiple decades in (1) mediation of racial/ethnic
      inequalities in mortality (between Maori and Europeans in New Zealand) by
      socioeconomic factors, (2) additional mediation through smoking, and (3)
      inequalities had there never been smoking. METHODS: We estimated natural (1 and 2
      above) and controlled mediation effects (3 above) in census-mortality cohorts for
      1981-1984 (1.1 million people), 1996-1999 (1.5 million), and 2006-2011 (1.5
      million) for 25- to 74-year-olds in New Zealand, using a weighting of regression
      predicted outcomes. RESULTS: Socioeconomic factors explained 46% of male
      inequalities in all three cohorts and made an increasing contribution over time
      among females from 30.4% (95% confidence interval = 18.1%, 42.7%) in 1981-1984 to
      41.9% (36.0%, 48.0%). Including smoking with socioeconomic factors only modestly
      altered the percentage mediated for males, but more substantially increased it
      for females, for example, 7.7% (5.5%, 10.0%) in 2006-2011. A counterfactual
      scenario of having eradicated tobacco in the past (but unchanged socioeconomic
      distribution) lowered mortality for all sex-by-ethnic groups and resulted in a
      12.2% (2.9%, 20.8%) and 21.2% (11.6%, 31.0%) reduction in the absolute mortality
      gap between Maori and Europeans in 2006-2011, for males and females,
      respectively. CONCLUSIONS: Our study predicts that, in this high-income country,
      reducing socioeconomic disparities between ethnic groups would greatly reduce
      ethnic inequalities in mortality over the long run. Eradicating tobacco would
      notably reduce ethnic inequalities in absolute but not relative mortality.

PMID- 29642086
TI  - Evidence for Efficacy of Treatment With the Anti-PD-1 Mab Nivolumab in Radiation
      and Multichemorefractory Advanced Penile Squamous Cell Carcinoma.
AB  - Penile squamous cell carcinoma (PeSCC) is a rare tumor and advanced PeSCC is
      associated with poor survival due to the aggressiveness of the disease and lack
      of effective systemic therapies. We describe for the first time a case with
      advanced chemoradiation refractory PeSCC who had documented response to active
      immunotherapy with the immune checkpoint inhibitor, anti-programmed death-1
      monoclonal antibody Nivolumab. The patient suffered from a poor prognosis human
      papillomavirus-negative PeSCC, with a somatic inactivation mutation of cyclin
      dependent kinase inhibitor 2A (CDKN2A) gene in tumor cells, and treatment with
      Nivolumab resulted in a partial response to therapy and significant tumor
      shrinkage. Histology transitions and alterations in tumor-infiltrating cytotoxic
      CD8 T-cell lymphocytes, programmed death ligand-1 expression on tumor cells and
      immune cells in tumor lesion biopsies pretreatment and posttreatment with
      Nivolumab were observed and described. In conclusion, in patients with metastatic
      PeSCC active immunotherapy combinations with an anti-programmed death
      1/programmed death ligand-1 agent may be beneficial and further relative clinical
      studies are required.

PMID- 29642087
TI  - Market and organizational factors associated with hospital vertical integration
      into sub-acute care.
AB  - BACKGROUND: Changes in payment models incentivize hospitals to vertically
      integrate into sub-acute care (SAC) services. Through vertical integration into
      SAC, hospitals have the potential to reduce the transaction costs associated with
      moving patients throughout the care continuum and reduce the likelihood that
      patients will be readmitted. PURPOSE: The purpose of this study is to examine the
      correlates of hospital vertical integration into SAC. METHODOLOGY/APPROACH: Using
      panel data of U.S. acute care hospitals (2008-2012), we conducted logit
      regression models to examine environmental and organizational factors associated
      with hospital vertical integration. Results are reported as average marginal
      effects. FINDINGS: Among 3,775 unique hospitals (16,269 hospital-year
      observations), 25.7% vertically integrated into skilled nursing facilities during
      at least 1 year of the study period. One measure of complexity, the availability
      of skilled nursing facilities in a county (ME = -1.780, p < .001), was negatively
      associated with hospital vertical integration into SAC. Measures of munificence,
      percentage of the county population eligible for Medicare (ME = 0.018, p < .001)
      and rural geographic location (ME = 0.069, p < .001), were positively associated
      with hospital vertical integration into SAC. Dynamism, when measured as the
      change county population between 2008 and 2011 (ME = 1.19e-06, p < .001), was
      positively associated with hospital vertical integration into SAC. Organizational
      resources, when measured as swing beds (ME = 0.069, p < .001), were positively
      associated with hospital vertical integration into SAC. Organizational resources,
      when measured as investor owned (ME = -0.052, p < .1) and system affiliation (ME
      = -0.041, p < .1), were negatively associated with hospital vertical integration
      into SAC. PRACTICE IMPLICATIONS: Hospital adaption to the changing health care
      landscape through vertical integration varies across market and organizational
      conditions. Current Centers for Medicare and Medicaid reimbursement programs do
      not take these factors into consideration. Vertical integration strategy into SAC
      may be more appropriate under certain market conditions. Hospital leaders may
      consider how to best align their organization's SAC strategy with their operating
      environment.

PMID- 29642088
TI  - Retaining nurses in a changing health care environment: The role of job
      embeddedness and self-efficacy.
AB  - BACKGROUND: Because nurses are on the front lines of care delivery, they are
      subject to frequent changes to their work practices. This change-laden
      environment puts nurses at higher risk for turnover. Given the frequent
      disruption to the way nurses perform their jobs, change-related self-efficacy
      (CSE), or confidence that one can handle change, may be vital to their retention.
      PURPOSE: The purpose of this article is to examine the roles of CSE and job
      embeddedness in reducing turnover intentions among nurses. Specifically, this
      article tests a model in which CSE is the intervening mechanism through which job
      embeddedness influences turnover intentions. METHODS: Drawing on a sample of 207
      nurses working in the medical/surgical unit of a major metropolitan hospital in
      the United States, this study employs OLS regression to test for direct effects
      of job embeddedness and CSE on turnover intentions and bias-corrected
      bootstrapping to test for the indirect effects of job embeddedness on turnover
      intentions through CSE. FINDINGS: Results show that CSE is directly linked to
      turnover intentions, and the effects of job embeddedness on turnover intentions
      become fully manifest through CSE. PRACTICE IMPLICATIONS: Improved nurse
      retention may lead to stable patient care and less disruption in service
      delivery. Improved retention also benefits health care organizations financially,
      as costs of replacing a nurse can exceed 100% of the salary for the position.
      Given the shortage of nurses in some geographic areas, retention remains an
      important goal.

PMID- 29642089
TI  - Evidence-Based Inclusion Criteria for Cochlear Implantation in Patients With
      Postlingual Deafness.
AB  - OBJECTIVES: This study determined the relationship between preoperative phoneme
      and word scores and the gain in speech perception after cochlear implantation in
      a large cohort of patients. The authors aimed to define evidence-based selection
      criteria for cochlear implantations in adults with postlingual deafness. DESIGN:
      This retrospective study included 364 adults with postlingual deafness who
      received a cochlear implant between 2000 and 2013 at the Leiden University
      Medical Center. The gain in speech perception observed postimplantation was
      compared with preoperative-aided/binaural speech perception scores, measured at
      65 dB SPL in quiet. Patients who showed preoperative phoneme scores on
      monosyllabic words above 50% were also tested for speech perception in the
      presence of speech-shaped background noise, at a +5 dB signal to noise ratio.
      RESULTS: Speech perception in quiet improved after implantation in all except 7
      patients. Average scores in quiet continued to improve, up to approximately 1
      year after implantation. When participants were divided into five groups, based
      on preoperative speech perception scores, all groups showed gains in speech
      perception, except for the group with aided preoperative phoneme scores above
      80%. However, all patients who were tested preoperatively with the addition of
      background noise showed improvements in speech perception in noise after the
      cochlear implantation. CONCLUSIONS: Although the decision to implant should
      consider individual ear differences and other factors that might apply to a
      particular case, based on our data, all patients with preoperative scores of
      either 80% (phonemes correct) or 60% (words correct) and lower in an optimal
      aided situation are potential candidates for a cochlear implant, provided that
      their preoperative speech perception score decreases below 50% (phonemes correct)
      or 20% (words correct), when background noise is added at a +5 dB signal to noise
      ratio.

PMID- 29642090
TI  - Global PA development: Time-consuming, complicated, and worthwhile.

PMID- 29642091
TI  - Mumps: Resurgence of a once-dormant disease.
AB  - Mumps is a systemic viral illness, preventable by vaccination, that typically
      affects children and is characterized by unilateral or bilateral swelling of the
      parotid glands. Uncommon complications such as orchitis, oophoritis, deafness,
      pancreatitis, aseptic meningitis, and encephalitis occur more often in adults.
      Recent outbreaks of the disease appear to be caused by a failure to maintain herd
      immunity in certain populations, particularly in affluent white communities. This
      article reviews the clinical manifestations, diagnosis, and potential
      complications in patients with mumps.

PMID- 29642092
TI  - Strategic foresight, leadership, and the future of rural healthcare staffing in
      the United States.
AB  - This article uses a strategic foresight tool, megatrends, to examine forces
      influencing long-term healthcare staffing in the rural United States. Two
      megatrends-exponential advances in science and technology and the continued
      evolution of the decentralized global marketplace-will influence and ultimately
      help shape the future of rural healthcare. Successful health ecosystems of the
      future will need to be customer-driven, more affordable, and tech-savvy.
      Successful evolution in an era of continuous change will require a blend of
      intentional engagement with stakeholders, strategic foresight, and future-focused
      leadership. More research is needed to fully understand not only the challenges
      of rural healthcare but also the emerging opportunities.

PMID- 29642093
TI  - Measuring the value of endoscopic retrograde cholangiopancreatography activity:
      an opportunity to stratify endoscopists on the basis of their value.
AB  - INTRODUCTION: As finite healthcare resources come under pressure, the value of
      physician activity is assuming increasing importance. The value in healthcare can
      be defined as patient health outcomes achieved per monetary unit spent. Even
      though some attempts have been made to quantify the value of clinician activity,
      there is little in the medical literature describing the importance of
      endoscopists' activity. This study aimed to characterize the value of endoscopic
      retrograde cholangiopancreatography (ERCP) performance of five
      gastroenterologists. PATIENTS AND METHODS: We carried out a retrospective
      prospective cohort study using the databases of patients undergoing ERCP between
      September 2014 and March 2017. We collected data from 1070 patients who underwent
      ERCP comparing value among the ERCPists at index ERCP. Procedure value was
      calculated using the formula Q/(T/C), where Q is the quality of procedure, T is
      the duration of procedure and C is the adjusted for complexity level. Quality and
      complexity were derived on a 1-4 Likert scale on the basis of American Society
      for Gastrointestinal Endoscopy criteria; time was recorded (in min) from
      intubation to extubation. Endoscopist time calculated from procedure time was
      considered a surrogate marker of cost as individual components of procedure cost
      were not itemized. RESULTS: In total, 590 procedures were analysed: 465
      retrospectively over 24 months and 125 prospectively over 6 months. There was a
      32% variation in the value of endoscopist activity in a more substantial
      retrospective cohort, with an even more considerable 73% variation in a smaller
      prospective arm. CONCLUSION: In an analysis of greater than 1000 ERCPs by a small
      cohort of experienced ERCPists, there was a wide variation in the value of
      endoscopist activity. Although the precision of estimating procedural costs needs
      further refinement, these findings show the ability to stratify ERCPists on the
      basis of the value their activity. As healthcare costs are scrutinized more
      closely, such value measurements are likely to become more relevant.

PMID- 29642096
TI  - Availability of a New Job-Exposure Matrix (CANJEM) for Epidemiologic and
      Occupational Medicine Purposes.
AB  - OBJECTIVE: The aim of this study was to introduce the Canadian job-exposure
      matrix (CANJEM). METHODS: Four large case-control studies of cancer were
      conducted in Montreal, focused on assessing occupational exposures by means of
      detailed interviews followed by expert assessment of possible occupational
      exposures. Thirty-one thousand six hundred seventy-three jobs were assessed using
      a checklist of 258 agents (listed with prevalences at http://expostats.ca/chems).
      This large exposure database was configured as a JEM. RESULTS: CANJEM is
      available in four occupational classification systems. It provides estimates of
      probability of exposure among workers with a given occupation, and for those
      exposed, various metrics of exposure. CANJEM can be accessed online
      (www.canjem.ca) or in a batch version. CONCLUSION: CANJEM is a large source of
      retrospective exposure information, covering most occupations and many agents.
      CANJEM can be used to support exposure assessment efforts in epidemiology and
      occupational health.

PMID- 29642095
TI  - Efficacy of Intra-articular Polynucleotides Associated With Hyaluronic Acid
      Versus Hyaluronic Acid Alone in the Treatment of Knee Osteoarthritis: A
      Randomized, Double-Blind, Controlled Clinical Trial.
AB  - OBJECTIVE: Pain and range of motion loss are the main clinical features of
      osteoarthritis (OA). Hyaluronic acid (HA) is one of the infiltrative therapies
      for OA treatment; however, its effectiveness is a matter of an ongoing debate in
      clinical practice. Polynucleotides (PNs), a DNA-derived macromolecule with
      natural origin and trophic activity, were found to favor cell growth and collagen
      production, in preclinical and clinical studies regarding cartilage regeneration.
      This study aimed at evaluating whether injection of PNs, in combination with HA
      [PNs associated with HA (PNHA)], can ameliorate pain and function of knees
      affected by OA, more than HA alone. DESIGN: A randomized, double-blind,
      controlled clinical trial. PATIENTS: The study enrolled 100 patients, then
      randomized to receive PNHA or HA alone (3 weekly knee I.A. injections).
      INTERVENTIONS AND MAIN OUTCOME MEASURES: Pain reduction, decrease of
      proinflammatory synovial fluid (SF) factors, and improvement in knee function
      were evaluated by Knee Society Score and WOMAC scores, after 2, 6, and 12 months
      and by biochemical and immunoenzymatic analyses of SF at the end of the
      treatment. RESULTS: Knee Society Score total score and pain item significantly
      ameliorated in both groups, showing better results in PNHA- than in the HA
      treated group. A significant reduction in the WOMAC score was observed over time
      for both groups. No significant adverse events were reported in either group.
      CONCLUSIONS: These findings suggest that I.A. injection of PNs, in combination
      with HA, is more effective in improving knee function and pain, in a joint
      affected by OA, compared with HA alone.

PMID- 29642094
TI  - Split-dose bowel cleansing with picosulphate is safe and better tolerated than 2
      l polyethylene glycol solution.
AB  - BACKGROUND: In physically less fit patients and patients requiring repeated
      exams, adequate bowel preparation for colonoscopy remains problematic,
      particularly because patients need to drink large volumes of unpleasant-tasting
      fluids. A further concern is potential unwarranted fluid shifts. AIMS: This study
      aimed to compare the safety and burden of a small-volume sodium
      picosulphate/magnesium citrate preparation (SPS-MC) with a 2-l ascorbic-acid
      enriched polyethylene glycol solution plus bisacodyl pretreatment (PEG-Asc+B).
      PATIENTS AND METHODS: Patients referred for colonoscopy were randomized to SPS-MC
      or PEG-Asc+B administered as a split-dose regimen. Patients received advice on
      the recommended 4-l SPS-MC and 2-l PEG-Asc+B fluid intake. Safety was assessed by
      blood sampling before and after the preparation and during a 30-day follow-up
      period. A questionnaire assessed tolerability and perceived burden of the
      preparation. RESULTS: A total of 341 patients underwent colonoscopy. Blood
      sampling showed a slight but significant decrease in sodium, chloride and
      osmolality and increase in magnesium in the SPS-MC group and a decrease in
      bicarbonate in the PEG-Asc+B group. Hyponatraemia and hypermagnesaemia without
      clinical signs were observed in 16 (14 SPS-MC) and 13 SPS-MC patients,
      respectively. Patients reported significantly fewer physical complaints and a
      significantly higher completion rate with SPS-MC. Patients receiving SPS-MC rated
      the intake as being easier and better tasting. In the event of a repeat
      colonoscopy, 59.7% of patients in the PEG-Asc+B and 93.6% of patients in the SPS
      MC group would opt for the same preparation again. CONCLUSION: Despite
      electrolyte shifts, both SPS-MC and PEG-Asc+B appeared clinically safe. From a
      patient's perspective, a small-volume preparation formula such as SPS-MC is
      preferred, resulting in fewer physical complaints and greater ease of intake.

PMID- 29642097
TI  - Patient Satisfaction Measurement in Occupational and Environmental Medicine
      Practice.
AB  - : High patient satisfaction is a desirable goal in medical care. Patient
      satisfaction measures are increasingly used to evaluate and improve quality in
      all types of medical practices. However, the unique aspects of occupational and
      environmental medicine (OEM) practice require development of OEM-specific
      measures and thoughtful interpretation of results. The American College of
      Occupational and Environmental Medicine has developed and recommends a set of
      specific questions to measure patient satisfaction in OEM, designed to meet
      anticipated regulatory requirements, facilitate quality improvement of
      participating OEM practices, facilitate case-management review, and offer fair
      and accurate assessment of OEM physicians.

PMID- 29642098
TI  - The Impact of Depression on Ill-Health Retirement and Its Moderating Factors:
      Analysis From the Korean Longitudinal Study of Aging (2006 to 2014).
AB  - OBJECTIVE: To investigate the effect of depressive symptoms on ill-health
      retirement (IHR). METHODS: Data were collected from the Korean Longitudinal Study
      of Ageing which conducted biennially from 2006 to 2014. IHR were defined as those
      who retired due to their health problems. The short-form Center for
      Epidemiological Studies-Depression scale served as outcome measure for definition
      of depressive symptoms. Hazard ratios of IHR were estimated by Cox regression.
      RESULTS: We observed that depressive symptoms significantly increased risk of IHR
      during 8-year follow-up period. Compared with those without depressive symptoms,
      depressed worker had 1.27-fold elevated risk for IHR. Subgroup analysis showed
      that the association between depressive symptoms and IHR is greater in the
      elders, women, and lower income group than the others. CONCLUSION: Depressive
      symptoms independently predicted IHR. Moreover, age, sex, and socioeconomic
      status modified these effects.

PMID- 29642099
TI  - Feasibility of Busulfan Melphalan and Stem Cell Rescue After 131I-MIBG and
      Topotecan Therapy for Refractory or Relapsed Metastatic Neuroblastoma: The French
      Experience.
AB  - High-risk neuroblastoma is characterized by poor long-term survival, especially
      for very high-risk (VHR) patients (poor response of metastases after induction
      therapy). The benefits of a tandem high-dose therapy and hematologic stem cell
      reinfusion (HSCR) have been shown in these patients. Further dose escalation will
      be limited by toxicity. It is thus important to evaluate the efficacy and
      tolerability of the addition of new agents such as I-MIBG (131Iode
      metaiodobenzylguanidine) to be combined with high-dose therapy in the
      consolidation phase. We report the feasibility of busulfan/melphalan (BuMel)
      after I-MIBG therapy with HSCR in patients with refractory or relapsed metastatic
      neuroblastoma. From November 2008 to March 2015, 9 patients received BuMel after
      I-MIBG therapy and topotecan. The main toxicity was digestive with only 1 patient
      developing grade 4 sinusoidal obstructive syndrome. Seven patients are alive at a
      median follow-up of 25 months. Among them, 2 are in ongoing complete remission
      and 1 in ongoing stable disease. These results suggest that BuMel with HSCR can
      be administered safely 2 months after I-MIBG therapy associated with topotecan
      for VHR patients. This strategy will be compared with tandem high-dose
      chemotherapy (thiotepa and busulfan-melphalan), followed by HSCR in the upcoming
      SIOPEN VHR Neuroblastoma Protocol.

PMID- 29642100
TI  - Bone and Inflammatory Responses to Training in Female Rowers over an Olympic
      Year.
AB  - INTRODUCTION/PURPOSE: To examine whether fluctuations in training load during an
      Olympic year lead to changes in bone mineral densities and factors that regulate
      bone (sclerostin, osteoprotegerin and receptor activator of nuclear factor kappa
      B ligand), energy metabolism (insulin-like growth factor-1 and leptin), and
      inflammation (tumor necrosis factor-alpha and interleukin 6) in elite heavyweight
      female rowers. METHODS: Blood samples were drawn from 15 female heavyweight
      rowers (27.0 +/- 0.8 yr, 80.9 +/- 1.3 kg, 179.4 +/- 1.4 cm) at baseline (T1-45 wk
      before Olympic Games) and after 7, 9, 20, 25, and 42 wk (T1-6, respectively).
      Ongoing nutritional counseling was provided. Total weekly training load was
      recorded over the week before each time point. Bone mineral density (BMD) was
      measured by dual energy x-ray absorptiometry at T1 and T6. RESULTS: Total BMD
      increased significantly before to after training (+0.02 g.cm), but was below the
      least significant change (+/-0.04 g.cm). Osteoprotegerin, insulin-like growth
      factor-1, and leptin remained stable across all time points. Fluctuations in
      training load (high vs low) were accompanied by parallel changes in tumor
      necrosis factor-alpha (2.1 +/- 0.2 vs 1.5 +/- 0.2 pg.mL), interleukin 6 (1.2 +/-
      0.08 vs 0.8 +/- 0.09 pg.mL), and sclerostin (high: 993 +/- 109 vs low: 741 +/-
      104 pg.mL). CONCLUSIONS: In this population of young female athletes with
      suitable energy availability, sclerostin and inflammation markers responded to
      fluctuations in training load, whereas BMD and bone mineral content were stable
      during the season, suggesting that training load periodization is not harmful for
      the bone health in athletes.

PMID- 29642102
TI  - Measuring Medical Housestaff Teamwork Performance Using Multiple Direct
      Observation Instruments: Comparing Apples and Apples.
AB  - PURPOSE: To examine the composition and concordance of existing instruments used
      to assess medical teams' performance. METHOD: A trained observer joined 20
      internal medicine housestaff teams for morning work rounds at Tufts Medical
      Center, a 415-bed Boston teaching hospital, from October through December 2015.
      The observer rated each team's performance using nine teamwork observation
      instruments that examined domains including team structure, leadership, situation
      monitoring, mutual support, and communication. Observations recorded on paper
      forms were stored electronically. Scores were normalized from 1 (low) to 5 (high)
      to account for different rating scales. Overall mean scores were calculated and
      graphed; weighted scores adjusted for the number of items in each teamwork
      domain. Teamwork scores were analyzed using t tests, pairwise correlations, and
      the Kruskal-Wallis statistic, and team performance was compared across
      instruments by domain. RESULTS: The nine tools incorporated five major domains,
      with 5 to 35 items per instrument, for a total of 161 items per observation
      session. In weighted and unweighted analyses, the overall teamwork performance
      score for a given team on a given day varied by instrument. While all of the
      tools identified the same low outlier, high performers on some instruments were
      low performers on others. Inconsistent scores for a given team across instruments
      persisted in domain-level analyses. CONCLUSIONS: There was substantial variation
      in the rating of individual teams assessed concurrently by a single observer
      using multiple instruments. Because existing teamwork observation tools do not
      yield concordant assessments, researchers should create better tools for
      measuring teamwork performance.

PMID- 29642101
TI  - Barriers and Facilitators to Self-Directed Learning in Continuing Professional
      Development for Physicians in Canada: A Scoping Review.
AB  - PURPOSE: This scoping review explored the barriers and facilitators that
      influence engagement in and implementation of self-directed learning (SDL) in
      continuing professional development (CPD) for physicians in Canada. METHOD: This
      review followed the six-stage scoping review framework of Arksey and O'Malley and
      of Daudt et al. In 2015, the authors searched eight online databases for English
      language Canadian articles published January 2005-December 2015. To chart and
      analyze data from the 17 included studies, they employed a two-step analysis
      process composed of conventional content analysis followed by directed coding
      applying the Theoretical Domains Framework (TDF). RESULTS: Conventional content
      analysis generated five categories of barriers and facilitators: individual,
      program, technological, environmental, and workplace/organizational. Directed
      coding guided by the TDF allowed analysis of barriers and facilitators to
      behavior change according to two key groups: physicians engaging in SDL, and SDL
      developers designing and implementing SDL programs. Of the 318 total barriers and
      facilitators coded, 290 (91.2%) were coded for physicians and 28 (8.8%) for SDL
      developers. The majority (209; 65.7%) were coded in four key TDF domains:
      environmental context and resources, social influences, beliefs about
      consequences, and behavioral regulation. CONCLUSIONS: This scoping review
      identified five categories of barriers and facilitators in the literature and
      four key TDF domains where most factors related to behavior change of physicians
      and SDL developers regarding SDL programs in CPD were coded. There was a
      significant gap in the literature about factors that may contribute to SDL
      developers' capacity to design and implement SDL programs in CPD.

PMID- 29642103
TI  - Social Accountability: A Framework for Medical Schools to Improve the Health of
      the Populations They Serve.
AB  - Social accountability has gained importance and greater acceptance in the ever
      increasing complexity and interconnectivity of patient care, education, and
      research that is the threefold mission of academic health science centers and
      networks. In this Invited Commentary, the author provides a brief overview of the
      development of the concept of social accountability and the criteria for the
      Association for Medical Education in Europe ASPIRE-to-Excellence Award for Social
      Accountability, which provide a useful framework for medical schools to consider
      when examining their own social accountability. Per these criteria, schools are
      expected to document social accountability plans in their organization and
      functions; document social accountability actions in their education and research
      program activities; and demonstrate positive impacts of their education,
      research, service, graduates, and partnerships on the health care and health of
      their community, region, and nation. Award-winning schools integrate social
      accountability into the school's mission, planning, and day-to-day management.
      The health needs and diversity of the school's community, region, and nation are
      reflected in the school's admissions, curriculum, learning experiences, research
      activities, health care partnerships, and graduates. The author also describes
      three award winners as exemplars of social accountability and concludes by
      challenging every medical school and graduate medical education program to focus
      on meeting the needs of the populations it serves, especially those who are
      marginalized, vulnerable, and underserved.

PMID- 29642104
TI  - Mixed Methods Convergent Study Designs in Health Professions Education Research:
      Toward Meaningful Integration of Qualitative and Quantitative Data.

PMID- 29642105
TI  - Illuminating Graduate Medical Education Outcomes in Order to Improve Them.
AB  - Optimizing clinician education is an essential step toward enhancing health
      outcomes, and graduate medical education (GME)-as the pipeline for producing the
      nation's physicians-is an appropriate target for improvement. This Invited
      Commentary focuses on the need to clarify the specific goals of GME and measure
      achievement of those goals, using consistent metrics. The authors report on an
      October 2017 National Academies of Sciences, Engineering, and Medicine (NASEM)
      workshop focused on this agenda. A broadly representative group of participants
      reflected strong consensus in support of using GME outcomes data to develop
      better approaches to education and related policy. Implementation challenges
      include identifying meaningful metrics, minimizing administrative burden,
      addressing privacy concerns, and recognizing variability in institutional mission
      and capabilities. The authors recommend creating a national inventory of current
      data sources and initiating a pilot program to collect and share common metrics,
      while advancing a national effort via a "neutral" convener, such as the NASEM.
      The authors assert that measuring and reporting GME outcomes is a professional
      responsibility that must now be tackled.

PMID- 29642106
TI  - Policy Change From the Centers for Medicare and Medicaid Services Provides an
      Opportunity to Improve Medical Student Education and Recruit Community
      Preceptors.
AB  - As U.S. medical educators know, it has been exceedingly difficult over the past
      decade to train medical students to document in the electronic health record
      (EHR) yet remain compliant with Centers for Medicare and Medicaid Services (CMS)
      guidelines. Indeed, some institutions have interpreted the guidelines to prohibit
      all medical student documentation in the EHR. This has been particularly
      challenging since the Association of American Medical Colleges has recommended
      that all medical school graduates be entrusted with 13 specific professional
      activities, two of which directly require student use of the EHR. Furthermore,
      critical efforts by clerkship directors to recruit community physicians as
      preceptors of medical students have been significantly hampered by the medical
      students' inability to document encounters. Therefore, the CMS policy transmittal
      Pub 100-04 Medicare Claims Processing Manual, released on February 2, 2018, which
      now explicitly allows appropriately supervised student documentation to be
      submitted for billing, is a welcome policy change. U.S. medical educators need to
      seize this opportunity, encourage their health systems to revise their internal
      precepting practices, and widely advertise to community preceptors that students
      can now add value in the clinical setting by assisting with documentation in the
      EHR.

PMID- 29642107
TI  - Estimation of Extra Length of Stay Attributable to Hospital-Acquired Infections
      in Adult ICUs Using a Time-Dependent Multistate Model.
AB  - OBJECTIVES: The objective of the study was to estimate the length of stay of
      patients with hospital-acquired infections hospitalized in ICUs using a
      multistate model. DESIGN: Active prospective surveillance of hospital-acquired
      infection from January 1, 1995, to December 31, 2012. SETTING: Twelve ICUs at the
      University of Lyon hospital (France). PATIENTS: Adult patients age greater than
      or equal to 18 years old and hospitalized greater than or equal to 2 days were
      included in the surveillance. All hospital-acquired infections (pneumonia,
      bacteremia, and urinary tract infection) occurring during ICU stay were
      collected. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The competitive
      risks of in-hospital death, transfer, or discharge were considered in estimating
      the change in length of stay due to infection(s), using a multistate model, time
      of infection onset. Thirty-three thousand four-hundred forty-nine patients were
      involved, with an overall hospital-acquired infection attack rate of 15.5% (n =
      5,176). Mean length of stay was 27.4 (+/- 18.3) days in patients with hospital
      acquired infection and 7.3 (+/- 7.6) days in patients without hospital-acquired
      infection. A multistate model-estimated mean found an increase in length of stay
      by 5.0 days (95% CI, 4.6-5.4 d). The extra length of stay increased with the
      number of infected site and was higher for patients discharged alive from ICU. No
      increased length of stay was found for patients presenting late-onset hospital
      acquired infection, more than the 25th day after admission. CONCLUSIONS: An
      increase length of stay of 5 days attributable to hospital-acquired infection in
      the ICU was estimated using a multistate model in a prospective surveillance
      study in France. The dose-response relationship between the number of
      hospitalacquired infection and length of stay and the impact of early-stage
      hospital-acquired infection may strengthen attention for clinicians to focus
      interventions on early preventions of hospital-acquired infection in ICU.

PMID- 29642108
TI  - Flexible Versus Restrictive Visiting Policies in ICUs: A Systematic Review and
      Meta-Analysis.
AB  - OBJECTIVES: To synthesize data on outcomes related to patients, family members,
      and ICU professionals by comparing flexible versus restrictive visiting policies
      in ICUs. DATA SOURCES: Medline, Scopus, and Web of Science. STUDY SELECTION:
      Observational and randomized studies comparing flexible versus restrictive
      visiting policies in the ICU and evaluating at least one patient-, family member
      , or ICU staff-related outcome. DATA EXTRACTION: Duplicate independent review and
      data abstraction. DATA SYNTHESIS: Of 16 studies identified for inclusion, seven
      were meta-analyzed. Most studies were rated as having a moderate risk of bias.
      Among patients, flexible visiting policies were associated with reduced frequency
      of delirium (odds ratio, 0.39; 95% CI, 0.22-0.69; I = 0%) and lower severity of
      anxiety symptoms (mean difference, -2.20; 95% CI, -3.80 to -0.61; I = 71%).
      Flexible visiting policies were not associated with increased risk of ICU
      mortality (odds ratio, 0.71; 95% CI, 0.38-1.36; I = 86%), ICU-acquired infections
      (odds ratio, 0.98; 95% CI, 0.68-1.42; I = 11%), or longer ICU stay (mean
      difference, -0.26 d; 95% CI, -0.57 to 0.05; I = 54%). Among family members,
      flexible visiting policies were associated with greater satisfaction. Among ICU
      professionals, flexible visiting policies were associated with higher burnout
      levels. CONCLUSIONS: Flexible ICU visiting hours have the potential to reduce
      delirium and anxiety symptoms among patients and to improve family members'
      satisfaction. However, they may be associated with an increased risk of burnout
      among ICU professionals. These conclusions are based on few studies, with small
      samples and moderate risk of bias.

PMID- 29642109
TI  - Hidradenitis Suppurativa-Like Condition Occurring After Microwave Sweat Gland
      Ablation.

PMID- 29642110
TI  - Modernizing the Mohs Surgery Consultation: Instituting a Video Module for
      Improved Patient Education and Satisfaction.
AB  - BACKGROUND: Studies show that patients recall less than half of the information
      given by their physicians. Use of video in medicine increases patient
      comprehension and satisfaction and decreases anxiety. However, studies have not
      elaborated on video content. OBJECTIVE: To use principles of learning with
      multimedia to improve the Mohs surgery consultation. MATERIALS AND METHODS: The
      authors developed 2 informational videos on Mohs surgery: traditional versus
      narrative. The focus of the traditional video was purely didactic. The narrative
      video included patient testimonials, patient-physician interaction, and
      animations. New Mohs surgery patients viewed either the traditional (n = 40) or
      the narrative video (n = 40). Existing Mohs surgery patients (n = 40) viewed both
      videos. Both groups answered questionnaires about their satisfaction. RESULTS:
      For new Mohs surgery patients, no significant difference was found between the
      traditional and the narrative video groups because respondent satisfaction was
      high for both video formats. For existing Mohs surgery patients, all respondents
      (100%) reported that videos were helpful for understanding Mohs surgery; however,
      the majority would recommend the narrative over the traditional format (72.5% vs
      27.5%, p = .01). CONCLUSION: Technology is useful for patient education because
      all patients preferred seeing a video to no video. Further research is needed to
      optimize effective multimedia use in patient education.

PMID- 29642112
TI  - Stepwise Surgical Treatment of Gnathophyma.

PMID- 29642111
TI  - Commentary on Swept-Source Optical Coherence Tomography-Supervised Biopsy.

PMID- 29642113
TI  - Efficacy of Denosumab for Glucocorticoid-Induced Osteoporosis in an Adolescent
      Patient with Duchenne Muscular Dystrophy: A Case Report.
AB  - CASE: We report the case of a 13-year-old boy with Duchenne muscular dystrophy
      (DMD) who sustained bilateral femoral neck fractures associated with
      glucocorticoid-induced osteoporosis. Denosumab therapy for 18 months markedly
      improved the lumbar bone mineral density and the bone turnover markers. No
      fractures or complications were recorded during the treatment period. CONCLUSION:
      To the best of our knowledge, this is the first description of denosumab
      treatment for glucocorticoid-induced osteoporosis in a patient with DMD. The drug
      merits additional testing as an effective therapy for osteoporosis in patients
      with DMD.

PMID- 29642114
TI  - Bilateral Neuropathy Dermatitis Following Simultaneous Bilateral Total Knee
      Arthroplasty: A Case Report.
AB  - CASE: A 65-year-old man developed bilateral knee dermatitis in the distribution
      of the infrapatellar nerve 3 months following uncomplicated simultaneous
      bilateral total knee arthroplasty (TKA) for osteoarthritis. The patient was
      treated with topical corticosteroids, and the rash had resolved after 6 months.
      At the 2-year follow-up, there had been no recurrences. CONCLUSION: Neuropathy
      dermatitis is a rare cutaneous complication of TKA. Although a few theories
      exist, there is no definitive explanation for the underlying pathophysiology of
      this disease process.

PMID- 29642117
TI  - Birth Month as a Risk Factor for the Diagnosis of Celiac Disease Later in Life: A
      Population-based Study.
AB  - Various perinatal factors have been implicated in association with the risk of
      developing celiac disease (CD) in genetically susceptible individuals. Our aim
      was to investigate the association of month and season of birth with the
      development of CD later in life in a large National cohort in Israel. Data were
      retrieved from a National database of more than 2 million Israeli Jewish
      adolescents born between 1971 and 1998. Overall, 10,566 CD cases out of 2,001,353
      subjects (0.53%) were identified and analyzed. CD risk was significantly higher
      for subjects born in May (odds ratio [OR] 1.07, P = 0.04) and June (OR 1.09, P =
      0.008). Birth during the winter season (December to February) showed a marginal
      significance toward reduced risk (OR 0.97, P = 0.05). In conclusion, children
      born in May and June are at increased risk for CD. This increased risk provides
      further evidence that perinatal environmental factors increase the risk of
      developing CD.

PMID- 29642118
TI  - Revisiting the Elastic Band Tourniquet in Pediatric Upper Limb Surgery.
AB  - Pediatric upper limb surgery requires fine tissue handling in a bloodless
      surgical field. Standard pneumatic tourniquets are often ineffective in the very
      young, as they do not fit all limb circumferences. We describe a simple and
      effective elastic band tourniquet technique and report our experience of safety
      with 113 cases.

PMID- 29642120
TI  - CDC Syphilis Summit: Difficult Clinical and Patient Management Issues.
AB  - Despite over a century of clinical experience in diagnosing and managing patients
      with syphilis, many thorny clinical questions remain unanswered. We focus on
      several areas of uncertainty for the clinician: the role of serological tests in
      diagnosing syphilis and assessing syphilis treatment responses, and the risk of
      neurosyphilis and ocular syphilis in patients with syphilis. We also address
      whether clinical approaches should differ in patients who are, and are not,
      infected with HIV. The current increases in syphilis rates in the US and
      elsewhere underscore our urgent need to definitively address these issues.

PMID- 29642115
TI  - Common and Dissociable Neural Activity After Mindfulness-Based Stress Reduction
      and Relaxation Response Programs.
AB  - OBJECTIVE: We investigated common and dissociable neural and psychological
      correlates of two widely used meditation-based stress reduction programs.
      METHODS: Participants were randomized to the Relaxation Response (RR; n = 18; 56%
      female) or the Mindfulness-Based Stress Reduction (MBSR; n = 16; 56% female)
      programs. Both programs use a "bodyscan" meditation; however, the RR program
      explicitly emphasizes physical relaxation during this practice, whereas the MBSR
      program emphasizes mindful awareness with no explicit relaxation instructions.
      After the programs, neural activity during the respective meditation was
      investigated using functional magnetic resonance imaging. RESULTS: Both programs
      were associated with reduced stress (for RR, from 14.1 +/- 6.6 to 11.3 +/- 5.5
      [Cohen's d = 0.50; for MBSR, from 17.7 +/- 5.7 to 11.9 +/- 5.0 [Cohen's d =
      1.02]). Conjunction analyses revealed functional coupling between ventromedial
      prefrontal regions and supplementary motor areas (p < .001). The disjunction
      analysis indicated that the RR bodyscan was associated with stronger functional
      connectivity of the right inferior frontal gyrus-an important hub of intentional
      inhibition and control-with supplementary motor areas (p < .001, family-wise
      error [FWE] rate corrected). The MBSR program was uniquely associated with
      improvements in self-compassion and rumination, and the within-group analysis of
      MBSR bodyscan revealed significant functional connectivity of the right anterior
      insula-an important hub of sensory awareness and salience-with pregenual anterior
      cingulate during bodyscan meditation compared with rest (p = .03, FWE corrected).
      CONCLUSIONS: The bodyscan exercises in each program were associated with both
      overlapping and differential functional coupling patterns, which were consistent
      with each program's theoretical foundation. These results may have implications
      for the differential effects of these programs for the treatment of diverse
      conditions.

PMID- 29642121
TI  - Sexually Transmitted Infection Prevalence in Women With HIV: Is There a Role for
      Targeted Screening?
AB  - BACKGROUND: Rates of sexually transmitted infections (STIs) and HIV are highest
      in the southern United States but vary widely by sex, age, and risk behavior.
      Current guidelines recommend annual screening for chlamydia, gonorrhea, syphilis,
      and trichomoniasis in all sexually active women with HIV. METHODS: Screening
      rates and test positivity for chlamydia, gonorrhea, syphilis, and trichomoniasis
      were determined per calendar year in this retrospective cohort study of women in
      care at an urban HIV clinic in Birmingham, Alabama, from 2013 to 2015. Chlamydia,
      gonorrhea, and trichomonas infections were detected by molecular diagnostics and
      syphilis by serology. A combined end point for chlamydia/gonorrhea/syphilis (STI
      3) was created based on similar test positivity and predictors. Predictors of STI
      3 were identified using logistic regression and generalized estimating equations.
      RESULTS: Among 745 women with HIV, median age was 46.8 years, 78.8% were black,
      and 61% were sexually active. In 2015, 83.7% of women were tested for STI. Test
      positivity was 1.0% for chlamydia, 0.5% for gonorrhea, 1.6% for syphilis, and
      13.3% for trichomoniasis. Independent predictors of STI-3 were recent chlamydia
      or gonorrhea (odds ratio [OR], 3.7; 95% confidence interval [CI], 1-13.4; P =
      0.047), public insurance compared with private (OR, 3.5; CI, 1-11.8; P = 0.048),
      and sex after drugs/alcohol (OR, 3.0; CI, 1.2-8.0; P = 0.025). Women 50 years or
      older were less likely to have STI (OR, 0.3; CI, 0.1-1; P = 0.040). CONCLUSIONS:
      In a cohort of women engaged in HIV care in the southern United States, detection
      of chlamydia, gonorrhea, and syphilis was infrequent but trichomoniasis was
      common. Many women screened for STI were low risk and universal testing
      strategies warrant evaluation.

PMID- 29642122
TI  - Lymphogranuloma Venereum Treatment and Terminology.

PMID- 29642123
TI  - The Spatial Architecture of Egocentric Sexual Networks: A New Framework or Just
      New Terms for Old Ideas?

PMID- 29642124
TI  - Embracing Negativity to Improve Work Environments.

PMID- 29642125
TI  - Holistic in the Hectic: Family Presence During Resuscitation in the Emergency
      Department.
AB  - Despite public knowledge of advanced directives and end-of-life wishes, desire
      for control over destiny often conflicts with the reality of end-of-life
      presentation. Recognized as best practice by both the Emergency Nurses
      Association and the American College of Emergency Physicians, family presence
      during resuscitation can actually prevent unintended harm to patients and their
      families.

PMID- 29642126
TI  - The Impact of Behavioral and Psychological Factors on Physical Fitness in Medical
      and Nursing Students.
AB  - Physical activity improves general health and quality of life. A stressful
      academic environment can increase both physical and mental health disruptions in
      medical and nursing students, negatively impacting physical activity and fitness.
      We explored the relationship between the fitness profiles of 202 medical and
      graduate nursing students with self-reported levels of general and emotional
      health to elucidate the role of the psychosocial factors involved in choosing to
      exercise.

PMID- 29642128
TI  - Rest Among African American Women: The Current State of the Science.
AB  - Effective health promotion among African American women requires knowledge and
      understanding of cultural influences and practices. This scoping review focused
      on rest, related concepts, and cultural perspectives and practices. We found a
      lack of conceptual distinction between fatigue and sleep and limited research on
      cultural meanings and practices of rest.

PMID- 29642127
TI  - Frankincense Essential Oil as a Supportive Therapy for Cancer-Related Fatigue: A
      Case Study.
AB  - Fatigue experienced by patients diagnosed with cancer can be debilitating and can
      be challenging to manage. The use of supportive therapies such as essential oils
      is gaining popularity among patients diagnosed with cancer. This article
      describes one patient's experience using frankincense (Boswellia carterii)
      essential oil to help in the management of her fatigue. The topical application
      of the frankincense helped to take her fatigue from being barely able to lift her
      head to being able to do some basic activities of daily living.

PMID- 29642129
TI  - The Effect of Spiritual Care on Adolescents Coping With Cancer.
AB  - People's experiences of living with cancer suggest that spirituality creates
      purpose and meaning in life for patients. Strengthening spirituality has positive
      effects on coping, mental health, and symptoms of the disease. This study
      examines the effect of spiritual care on adolescents coping with cancer. This
      research is a single-group, quasi-experimental, pre-/poststudy conducted on 32
      adolescents. The spiritual care program was presented individually and face to
      face over six 45-minute sessions held on the admission days. Data were collected
      using the Ways of Coping Questionnaire by Lazarus and Folkman. A significant
      difference was observed between the pretest and posttest mean values in all the
      coping subscales, which suggests the effect of spiritual care on adolescents'
      coping with cancer, but no significant differences were observed between the
      posttest and follow-up mean values, which shows the importance of the continuity
      of spiritual care in adolescent patients. According to the results, spirituality
      based care programs offered by nurses can positively affect adolescents' coping
      with cancer and improve their overall coping.

PMID- 29642130
TI  - Effectiveness of Integrative Restoration (iRest) Yoga Nidra on Mindfulness,
      Sleep, and Pain in Health Care Workers.
AB  - This article examines the effectiveness of Integrative Restoration (iRest) Yoga
      Nidra meditation on mindfulness, sleep, and pain in health care workers. As
      health care workers provide emotional support to patients, it is not uncommon for
      workers to experience both physical and mental exhaustion. One holistic approach
      to support employees is mindfulness training. iRest Yoga Nidra is a complementary
      and integrative health therapy that increases mindfulness. A pre
      /postinterveniton descriptive survey design was used. Before and after
      experiencing iRest meditation, participants completed a 51-item questionnaire
      consisting of demographics plus 3 validated instruments: the Five-Facet
      Mindfulness Questionnaire (FFMQ), the Epworth Sleepiness Scale (ESS), and
      Department of Defense/Veterans Administration (DoD/VA) Pain Supplemental
      Questions (PSQ). A total of 15 participants completed both questionnaires.
      Postintervention FFMQ scores were significantly higher than preintervention (z = 
      3.294, P = .001). The highest subscale scores were "acting with awareness" and
      "nonjudging of inner experience." There was a not a significant difference in the
      mean ESS scores at baseline and follow-up. However, there was a strong negative
      correlation between the mean ESS improvement score and the number of weeks
      attended (rs = -0.705, P = .003). There was a not a significant difference in the
      mean pain baseline and follow-up scores. This study showed significant
      improvement in mindfulness of health care workers following a guided 8-week iRest
      Yoga Nidra program. The results of this study may provide some insight into
      helping health care workers deal with the demands of their profession in a
      positive manner, thus leading to an improved workplace environment.

PMID- 29642131
TI  - Bath Bombs: The Power of Self-care Amongst Bubbling Discord.

PMID- 29642132
TI  - The Nutrition-Brain Connection: Nutritional Status and Cognitive Decline.

PMID- 29642133
TI  - Nurses' Sleepiness and Sleeplessness: The Epidemic of Insufficient Sleep.

PMID- 29642135
TI  - The Development of Kyphosis and Lordosis in the Growing Spine.
AB  - STUDY DESIGN: A longitudinal cohort study. OBJECTIVE: The aim of this study was
      to do the analysis of the development of kyphosis and lordosis in the growing
      spine. SUMMARY OF BACKGROUND DATA: Previous studies have measured kyphosis and
      lordosis in different ways with differing techniques. None of the previous
      literature has a truly longitudinal design and there is disagreement as to
      whether there exists a difference between the development of kyphosis and
      lordosis between males and females. METHODS: Repeated measures using Integrated
      Shape Imaging System Integrated Shape Imaging System 2 surface topography over 5
      years of a group of children aged 5 to 16 years without spinal deformity.
      Longitudinal analysis was performed using linear mixed effects modeling. RESULTS:
      There were 638 measures in 194 children. Both kyphosis and lordosis increased
      with age in both males and females (P < 0.001 for kyphosis and P = 0.002 for
      lordosis). There was no statistical difference in the development of kyphosis
      between males and females (P = 0.149). However, there was a significant
      difference in lordosis between males and females (P < 0.001) with female lordosis
      larger than that seen in males. Kyphosis and lordosis increased in a nonlinear
      fashion with age. CONCLUSION: Kyphosis and lordosis increase as children age.
      Between males and females there is no difference in the increase in the size of
      kyphosis, but there is difference in the size of lordosis with females having
      greater lordosis versus males at the same age. LEVEL OF EVIDENCE: 2.

PMID- 29642134
TI  - Effect of Diallyl Trisulfide on Ischemic Tissue Injury and Revascularization in a
      Diabetic Mouse Model.
AB  - BACKGROUND AND OBJECTIVE: Allitridin [diallyl trisulfide (DATS)] is an extract
      from garlic (Allium sativum) that putatively improves endothelial function and is
      protective against cardiovascular diseases. Endothelial dysfunction after tissue
      ischemia in diabetic patients is partially due to poor angiogenic response. This
      study investigated whether DATS may improve angiogenesis in a diabetic mouse
      model with hind limb ischemia. METHODS: Streptozotocin was administered by
      intraperitoneal injection to establish the model of diabetes in male C57BL/6
      mice. After 14 days, nondiabetic and diabetic mice (n = 24, each) underwent
      unilateral hind limb ischemia by femoral artery ligation. The mice were
      apportioned to 4 groups: nondiabetic treated (or not) with DATS and diabetic
      treated (or not) with DATS. DATS treatment consisted of a single daily
      intraperitoneal injection of 500 MUg.kg.d for 14 days, beginning on the day of
      induced ischemia. Ischemia was scored by standard criteria. Blood perfusion was
      determined using thermal infrared imaging. Tissue capillary density and oxidative
      stress levels were measured by immunohistochemistry and immunofluorescence,
      respectively. Serum lipids were measured by enzymatic colorimetric assay. Fasting
      serum insulin was detected using an insulin enzyme-linked immunosorbent assay
      kit. Nitric oxide (NO) metabolites and protein carbonyls in tissues were
      determined by enzyme-linked immunosorbent assay. Targeted protein concentrations
      were measured by western blotting. RESULTS: At 14 days after ligation, the
      ischemic skeletal muscle of the streptozotocin-induced diabetic mice had lower
      levels of endothelial NO synthase, phosphorylated endothelial NO synthase, and
      vascular endothelial growth factor compared with nondiabetic group. In addition,
      the hind limb blood perfusion, capillary density, and NO bioactivity were lower
      in the diabetic group, whereas oxidative stress and protein carbonyl levels were
      higher. These changes were ameliorated by DATS treatment. CONCLUSIONS: DATS
      treatment of diabetic mice promoted revascularization in ischemic tissue.

PMID- 29642136
TI  - The Seven-Year Cost-Effectiveness of Anterior Cervical Discectomy and Fusion
      Versus Cervical Disc Arthroplasty: A Markov Analysis.
AB  - STUDY DESIGN: Markov model analysis. OBJECTIVE: The aim of this study was to
      determine the 7-year cost-effectiveness of single-level anterior cervical
      discectomy and fusion (ACDF) versus cervical disc replacement (CDR) for the
      treatment of cervical disc degeneration. SUMMARY OF BACKGROUND DATA: Both ACDF
      and CDR are acceptable surgical options for the treatment of symptomatic cervical
      disc degeneration. Past studies have demonstrated at least equal effectiveness of
      CDR when compared with ACDF in large randomized Investigational Device Exemption
      (IDE) studies. Short-term cost-effectiveness analyses at 5 years have suggested
      that CDR may be the preferred treatment option. However, adjacent segment disease
      and other postoperative complications may occur after 5 years following surgery.
      METHODS: A Markov model analysis was used to evaluate data from the LDR Mobi-C
      IDE study, incorporating five Markov transition states and seven cycles with each
      cycle set to a length of 1 year. Transition state probabilities were determined
      from complication rates, as well as index and adjacent segment reoperation rates
      from the IDE study. Raw SF-12 data were converted to health state utility values
      using the SF-6D algorithm for 174 CDR patients and 79 ACDF patients. RESULTS:
      Assuming an ideal operative candidate who is 40-years-old and failed appropriate
      conservative care, the 7-year cost was $103,924 for ACDF and $105,637 for CDR.
      CDR resulted in the generation of 5.33 quality-adjusted life-years (QALYs), while
      ACDF generated 5.16 QALYs. Both ACDF and CDR were cost-effective, but the
      incremental cost-effectiveness ratio (ICER) was $10,076/QALY in favor of CDR,
      which was less than the willingness-to-pay (WTP) threshold of $50,000/QALY.
      CONCLUSION: ACDF and CDR are both cost-effective strategies for the treatment of
      cervical disc degeneration. However, CDR is the more cost-effective procedure at
      7 years following surgery. Further long-term studies are needed to validate the
      findings of this model. LEVEL OF EVIDENCE: 1.

PMID- 29642137
TI  - Outpatient Posterior Lumbar Fusion: A Population-Based Analysis of Trends and
      Complication Rates.
AB  - STUDY DESIGN: A retrospective case-control study. OBJECTIVE: The aim of this
      study was to determine the nationwide trends and complication rates associated
      with outpatient posterior lumbar fusion (PLF). SUMMARY OF BACKGROUND DATA:
      Outpatient lumbar spine fusion is now possible secondary to minimally invasive
      techniques that allow for reduced hospital stays and analgesic requirements.
      Limited data are currently available regarding the clinical outcome of outpatient
      lumbar fusion. METHODS: The Humana administrative claims database was queried for
      patients who underwent one to two-level PLF (CPT-22612 or CPT-22633 AND ICD-9
      816.2) as either outpatients or inpatients from Q1 2007 to Q2 2015. The incidence
      of perioperative medical and surgical complications was determined by querying
      for relevant International Classification of Diseases and Current Procedural
      Terminology codes. Multivariate logistic regression adjusting for age, gender,
      and Charlson Comorbidity Index was used to calculate odds ratios (ORs) of
      complications among outpatients relative to inpatients undergoing PLF. RESULTS:
      Cohorts of 770 patients who underwent outpatient PLF and 26,826 patients who
      underwent inpatient PLF were identified. The median age was in the 65 to 69 years
      age group for both cohorts. The annual relative incidence of outpatient PLF
      remained stable across the study period (R = 0.03, P = 0.646). Adjusting for age,
      gender, and comorbidities, patients undergoing outpatient PLF had higher
      likelihood of revision/extension of posterior fusion [(OR 2.33, confidence
      interval (CI) 2.06-2.63, P < 0.001], anterior fusion (OR 1.64, CI 1.31-2.04, P <
      0.001), and decompressive laminectomy (OR 2.01, CI 1.74-2.33, P < 0.001) within 1
      year. Risk-adjusted rates of all other postoperative surgical and medical
      complications were statistically comparable. CONCLUSION: Outpatient lumbar fusion
      is uncommonly performed in the United States. Data collected from a national
      private insurance database demonstrate a greater risk of postoperative surgical
      complications including revision anterior and posterior fusion and decompressive
      laminectomy. Surgeons should be cautious in performing PLF in the outpatient
      setting, as the risk of revision surgery may increase in these cases. LEVEL OF
      EVIDENCE: 3.

PMID- 29642138
TI  - Paraneoplastic sensorimotor polyneuropathy in prostatic adenocarcinoma: A case
      report.
AB  - RATIONALE: Paraneoplastic syndrome is a very rare syndrome among prostate cancer
      patients. In particular, paraneoplastic sensorimotor neuropathy has never been
      reported as a complication of prostatic adenocarcinoma. PATIENT CONCERNS: A 75
      year-old man who was diagnosed with prostatic adenocarcinoma with multiple
      metastases received cancer treatment. But, numbness and tingling sensations in
      both sides of the upper and lower limbs got progressively worse. DIAGNOSESE: He
      was diagnosed with positive anti-Hu antibodies paraneoplastic sensorimotor
      polyneuropathy caused by prostatic adenocarcinoma. INTERVENTIONS: The patient
      received physical therapy, occupational therapy, and opioid medication during 3
      weeks at cancer rehabilitation department during 3 weeks. OUTCOMES: There was no
      improvement in functional outcome in this patient. But, the patient's neuropathic
      pain was improved by the use of opioid agents. LESSONS: This case report is the
      first to report anti-Hu antibody-positive paraneoplastic sensorimotor neuropathy
      in a patient with adenocarcinoma of the prostate.

PMID- 29642139
TI  - Antenatal screening and diagnosis of tuberous sclerosis complex by fetal
      echocardiography and targeted genomic sequencing.
AB  - Although fetal cardiac rhabdomyoma can be the initial finding in patients with
      tuberous sclerosis complex (TSC), the challenges of precise genetic diagnosis of
      TSC can now be potentially overcome by new whole or targeted genomic sequencing.
      The goals of this study were to investigate the correlation between suspected
      cardiac rhabdomyoma and TSC to provide the information for a prenatal diagnosis
      of TSC and to validate the TSC genotype in this cohort of fetuses with suspected
      prenatal cardiac rhabdomyoma.We retrospectively analyzed 10,728 fetal
      echocardiograms from January 2013 to March 2016 in our institution. A total of 32
      fetuses were suspected of having cardiac rhabdomyomas. Among them, 15 subjects
      met the inclusion criteria and provided written consent. Samples from fetuses (n
      = 13 after terminations) and newborns (n = 2) were available for targeted genomic
      sequencing of the exons and introns of the TSC1 and TSC2 genes and the adjacent
      10 base pairs and for validated studies using Sanger sequencing.Among the 15
      subjects with suspected cardiac rhabdomyoma and TSC genomic sequencing data, 7
      subjects were familial and 8 subjects were sporadic cases. Fetal echocardiography
      showed a single tumor in 2 fetuses and multiple tumors in 13 fetuses. Gene
      sequencing analysis showed no mutation of the TSC1 or TSC2 gene in 2 subjects
      with a single tumor but positive mutations in all 13 subjects with multiple
      tumors. Among the latter, 5 mutations were "pathogenic" and have been previously
      reported (4 familial and 1 sporadic). Six new mutations were "likely pathogenic"
      and had not been previously reported (3 familial and 3 sporadic); 1 was of
      "uncertain significance" (sporadic), and 1 was suspected of being "likely benign"
      (sporadic).Prenatal suspected cardiac rhabdomyoma detected by fetal
      echocardiography should raise the suspicion of TSC. In fetuses with multiple
      tumors, especially the familial cases, genomic sequencing has a high yield of
      detecting TSC-causing genes. Patient history, prenatal fetal echocardiography,
      and targeted genomic sequencing may facilitate screening for, diagnosis of, and
      counseling for TSC.

PMID- 29642140
TI  - Statins in adult patients with HIV: Protocol for a systematic review and network
      meta-analysis.
AB  - BACKGROUND: Patients with HIV have been found to suffer from lipid abnormalities,
      including elevated levels of total and LDL-cholesterol as well as triglyceride
      levels. Abnormal lipid levels are associated with an increased risk of developing
      cardiovascular diseases, which are significant causes of mortality among the
      general population. Therefore, the objective of the current study is to conduct a
      systematic review with network meta-analysis to compare the effects of statins
      classes on HIV patients. METHODS: Randomized clinical trials (RCTs) and
      observational studies published in English up to 31 December 2017, and which
      include direct and/or indirect evidence, will be included. Studies will be
      retrieved by searching four electronic databases and cross-referencing. Dual
      selection and abstraction of data will occur. The primary outcome will all-cause
      mortality, new event of acute myocardial infarction, stroke (hemorrhagic and
      ischemic), hospitalization for acute coronary syndrome and urgent
      revascularization procedures and cardiovascular mortality. Secondary outcomes
      will be assessment of the differences in change of total cholesterol (TC), low
      density lipoprotein (LDL-C), apolipoprotein B (ApoB), high density lipoprotein
      (HDL-C). Risk of bias will be assessed using the Cochrane Risk of Bias assessment
      instrument for RCTs and the Strengthening the Reporting of Observational Studies
      in Epidemiology instrument for observational studies. Network meta-analysis will
      be performed using multivariate random-effects meta-regression models. The
      surface under the cumulative ranking curve will be used to provide a hierarchy of
      statins that reduce cardiovascular mortality in HIV patients. A revised version
      of the Cochrane Risk of Bias tool (RoB 2.0) will be used to assess the risk of
      bias in eligible RCTs. Results will be synthesized and analyzed using network
      meta-analysis (NMA). Overall strength of the evidence and publication bias will
      be evaluated. Subgroup and sensitivity analysis will also be performed. RESULTS
      AND CONCLUSION: Ethics approval was not required for this study because it was
      based on published studies. The results and findings of this study will be
      submitted and published in a scientific peer-reviewed journal. The evidence will
      determine which combination of interventions are most promising for current
      practice and further investigation. TRIAL REGISTRATION NUMBER: PROSPERO
      (CRD42017072996).

PMID- 29642141
TI  - A case report of frozen elephant trunk combined with endovascular treatment for
      acute aortic dissection of Kommerell's diverticulum involving right aortic arch
      and descending aorta.
AB  - RATIONALE: Acute aortic dissection of Kommerell's diverticulum in the right
      aortic arch is extremely rare. There are several different procedures for the
      disease. With advances in endovascular treatment, hybrid surgical and
      endovascular management may provide a treatment of choice for this kind of
      disease. PATIENT CONCERNS: A 43-year-old man was admitted to the hospital with
      intermittent pain of left arm, chest, and back. DIAGNOSES: Computed tomography
      demonstrated an aberrant left subclavian artery originating from Kommerell's
      diverticulum in the right aortic arch, acute aortic dissection of Kommerell's
      diverticulum involving arch and descending aorta. INTERVENTIONS: Total arch
      replacement combined with frozen elephant trunk was performed to create an
      adequate landing zone through a median sternotomy by circulatory arrest. Thoracic
      endovascular aortic repair was performed to isolate Kommerell's diverticulum from
      descending aorta completely, extending from the frozen elephant trunk to the
      distal descending aorta at the same time. OUTCOMES: The patient got an uneventful
      postoperative course. LESSONS: Hybrid surgical and endovascular management is a
      safe and effective procedure for this rare disease.

PMID- 29642142
TI  - Peroral endoscopic cardial constriction in gastroesophageal reflux disease.
AB  - Gastroesophageal reflux disease (GERD) is a major digestive health problem with a
      high and increasing incidence worldwide. Peroral endoscopic cardial constriction
      (PECC) was developed by our group to provide a less invasive treatment for
      GERD.In this preliminary follow-up study, 16 patients were enrolled and 13
      patients with GERD were targeted for analysis according to the Los Angeles
      classification of reflux esophagitis. The GERD health-related quality of life
      (GERD-HRQL) scale and esophageal pH monitoring were applied to assess clinical
      efficiency at 3 and 6 months after PECC treatment, respectively.All GERD patients
      successively received PECC, and no severe treatment-related complication was
      reported. Before PECC treatment, the GERD-HRQL scale was 19.92 +/- 7.89. At 3 and
      6 months after treatment, the GERD-HRQL scale was 4.46 +/- 4.31 and 5.69 +/-
      5.07, respectively. DeMeester score was 125.50 +/- 89.64 before PECC treatment,
      and 16.97 +/- 12.76 and 20.32 +/- 15.22 at 3 and 6 months after PECC treatment.
      Furthermore, the fraction time of a pH below 4 significantly decreased at 3 and 6
      months after PECC treatment. Fraction time at pH <4 was 35.55 +/- 26.20 before
      PECC treatment and 7.96 +/- 13.03 and 4.72 +/- 3.78 at 3 and 6 months after PECC
      treatment, respectively. These results suggest that PECC treatment could
      significantly reduce the GERD-HRQL scale and DeMeester score (P < .01).PECC is a
      feasible, safe, and effective method to treatment GERD through narrowing the
      diameter of the cardia and preventing the reflux of stomach contents.

PMID- 29642143
TI  - Small bowel capsule endoscopy revealing neuromuscular and vascular hamartoma of
      the jejunum: A case report.
AB  - RATIONALE: Digestive hemorrhage is a life-threatening and represents for both
      clinicians and patient a challenger problematic condition with the urgencies to
      discover the origin for correct the cause and safe the life of patient. PATIENT
      CONCERNS: We report the case of a 58 -year-old man with extremely rare
      hamartomatous neurovascular lesion. Following recurrent episode of intestinal
      hemorrhage the patient underwent small bowel capsule endoscopy. DIAGNOSES:
      Diagnosed with small intestine neoplasia. INTERVENTIONS: The patient underwent
      curative small bowel resection. Histologic diagnosis was neuromuscular and
      vascular hamartoma (NMVH). In the small intestine, neoplastic lesions are very
      rare (2%) and mostly malformative while the more frequent cause of cryptic
      digestive hemorrhage remains angiodysplasia (50%) . The preexisting NMVH was
      exacerbated by the use of non-steroidal anti-inflammatory drugs, causing
      hemorrhage due to diffuse ulceration. OUTCOMES: The patient stay healthy after
      treatment. LESSONS: This is an hemorrhagic lesion with macroscopic "neoplastic"
      patterns due to abnormal mixing of normal indigenous tissue components. It poses
      a diagnostic challenge for clinicians and pathologists, but diagnosis is
      facilitated by capsule endoscopy and surgical treatment should provide definitive
      resolution.

PMID- 29642144
TI  - Lectin microarray and mass spectrometric analysis of hepatitis C proteins reveals
      N-linked glycosylation.
AB  - We used lectin microarray and mass spectrometric analysis to identify the N
      linked glycosylation patterns of hepatitis C virus (HCV) particles. HCV J6/JFH-1
      chimeric cell culture (HCVcc) in the culture supernatant was concentrated and
      purified by ultrafiltration and sucrose gradient ultracentrifugation. Twelve
      fractions were collected from the top and analyzed for viral infectivity and HCV
      RNA content after sucrose gradient separation. HCV RNA and proteins were
      separated by ultracentrifugation in a continuous 10% to 60% sucrose gradient to
      purify viral particles based on their sedimentation velocities. HCVcc particles
      were found mainly in fractions 6 to 8, as determined by quantitative polymerase
      chain reaction (qPCR) analysis for HCV RNA and ELISA of the HCV core protein. The
      N-glycans on HCV proteins were analyzed by lectin microarray and mass
      spectrometry. We identified that 32 of 37 lectins displayed the positive binding
      signals and 16 types of N-glycoforms of which the major HCV glycoforms were high
      mannose-type N-linked oligosaccharides, hybrid N-glycans, and fucosylated N
      glycans. Our study provided new detailed information regarding the majority of
      the glycan-protein profile, complementing to previous findings of glycan-HCV
      protein interactions.

PMID- 29642145
TI  - Intra-articular injection of methylprednisolone for reducing pain in knee
      osteoarthritis: A systematic review and meta-analysis.
AB  - BACKGROUND: To evaluate the efficacy and safety of intra-articular
      methylprednisolone for reducing pain in patients with knee osteoarthritis.
      METHODS: We conduct electronic searches of Medline (1966-2017.11), PubMed (1966
      2017.11), Embase (1980-2017.11), ScienceDirect (1985-2017.11), and the Cochrane
      Library (1900-2017.11) for randomized clinical trials comparing the use of
      methylprednisolone to treat knee osteoarthritis. The primary outcomes are Western
      Ontario and McMaster Universities Arthritis Index (WOMAC) pain scores and WOMAC
      function scores. Each outcome was combined and calculated using the statistical
      software STATA 12.0. Fixed/random effect model was adopted based on the
      heterogeneity tested by I statistic. RESULTS: A total of 739 patients were
      analyzed across 4 randomized controlled trials (RCTs). The present meta-analysis
      revealed that there were significant differences between groups regarding the
      WOMAC pain scores at 4 weeks (WMD = -1.384, 95% CI: -1.975 to -0.793, P = .000),
      12 weeks (WMD = -1.587, 95% CI: -2.489 to -0.685, P = .001), and 24 weeks (WMD = 
      1.563, 95% CI: -2.245 to -0.881, P = .000). Significant differences were
      identified in terms of physical function at 4 weeks (WMD = -7.925, 95% CI: 
      13.359 to -2.491, P = .004), 12 weeks (WMD = -7.314, 95% CI: -13.308 to -1.320, P
      = .117), and 24 weeks (WMD = -6.484, 95% CI: -11.256 to -1.711, P = .008).
      CONCLUSION: Intra-articular methylprednisolone injection was associated with an
      improved pain relief and physical function in patients with knee osteoarthritis.
      Additionally, no severe adverse effects were observed. Due to the limited quality
      of the evidence currently available, higher quality RCTs were required.

PMID- 29642146
TI  - Comparison of angiotensin-converting enzyme inhibitors and angiotensin II
      receptor blockers on cardiovascular outcomes in hypertensive patients with type 2
      diabetes mellitus: A PRISMA-compliant systematic review and meta-analysis.
AB  - BACKGROUND: Previous studies seem to show different effects of angiotensin
      converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) on
      cardiovascular (CV) events in hypertensive patients with type 2 diabetes mellitus
      (T2DM). Our objective was to analyze which are preferable on the incidence of all
      cause mortality, CV death, and major CV events in hypertensive patients with
      T2DM. METHODS: PubMed, MEDLINE, and EMBASE were searched for randomized
      controlled trials (RCTs) published up to June 2016 with ACEI or ARBs as the
      intervention for hypertensive patients with T2DM. The primary end points were all
      cause mortality and CV death. The secondary end points were myocardial infarction
      (MI), stroke, heart failure (HF), and CV events. Two investigators extracted the
      information independently. Data were pooled using a fixed-effects model or a
      random-effects model if significant heterogeneity was present. RESULTS: A total
      of 13 trials were included for analysis, 5 ACEI trials (24,976 patients) and 8
      ARB trials (22,032 patients) followed for a mean of 3.8 years. Treatment with
      ACEI was associated with significantly reduction in all-cause mortality [odds
      ratio (OR) 0.87; 95% confidence interval (95% CI), 0.80-0.94], CV death (OR 0.81;
      95% CI, 0.68-0.98), and other CV outcomes such as MI (0R 0.77; 95% CI, 0.66
      0.90), stroke (OR 0.88; 95% CI, 0.78-0.99), HF (OR 0.65; 95% CI, 0.47-0.90), and
      CV events (OR 0.83; 95% CI, 0.73-0.95), whereas ARBs therapy had no significant
      reduction in the results of many primary and secondary outcomes. CONCLUSION: This
      meta-analysis suggests that treatment with ACEI showed a significant CV
      protection for all-cause mortality, CV death, and major CV events, whereas ARBs
      had no benefits on these outcomes except MI. In consideration of high mortality
      and morbidity, ACEI was preferable than ARBs on patients with hypertension and
      T2DM.

PMID- 29642147
TI  - The research status of immune checkpoint blockade by anti-CTLA4 and anti-PD1/PD
      l1 antibodies in tumor immunotherapy in China: A bibliometrics study.
AB  - PURPOSE: Using bibliometrics, we analyzed the research status of immune
      checkpoint blockade (ICB, a popular tumor immunotherapy method represented by
      antibodies targeted CTLA-4 and PD-1/PD-L1) in tumor immunotherapy in China during
      the past 2 decades. METHODS: Articles in Science Citation Index Expanded (SCI
      EXPANDED), patents in Thomson Innovation, and drugs in Cortellis Competitive
      Intelligence in the field of ICB for tumor immunotherapy from 1996 to 2015 were
      the subjects of bibliometric analysis. Using database-attached software and
      Excel, quantitative analyses were performed including examination of the number
      of documents, citation frequency, h-index, key projects, quantity of
      publications, public patents, and status of new drug research. RESULTS: The
      number of publications from 1996 to 2015 in the field of ICB for tumor
      immunotherapy that came out of China was 380, which was 14.3% of the total
      publications worldwide and was second only to that of the USA. In the past
      decade, China has rapidly increased the number of publications and patents in
      this field. However, indicators of publication influence, such as citation
      frequency and h-index, were far behind other advanced countries. In addition, the
      total number of patents in China was much lower than that of the USA. China has
      introduced 5 drugs for ICB that are being developed for the healthcare market.
      CONCLUSION: Tumor immunotherapy research such as ICB in China has developed
      rapidly with increasing influence in the last 2 decades. However, there is still
      a relatively large gap compared with the USA. It is expected that China will have
      greater influence on tumor immunotherapy research in the near future.

PMID- 29642148
TI  - Turning the backbone into an ankylosed concrete-like structure: Case report.
AB  - RATIONALE: Progressive restriction of the spinal bio-mechanics is not-uncommon
      deformity encountered in spine clinics. Congenital spinal fusion as seen in
      Klippel-Feil-anomaly, progressive non-infectious anterior vertebral fusion, and
      progressive spinal hyperostosis secondary to ossification of the anterior
      longitudinal spinal ligament are well delineated and recognized. PATIENT
      CONCERNS: A 24-year-old girl has history of osteoporosis since her early
      childhood, associated with multiple axial and appendicular fractures and
      scoliosis. Recently she presented with episodes of severe back pain, spinal
      rigidity/stiffness with total loss of spine biomechanics. DIAGNOSES: She was
      provisionally diagnosed as having osteogenesis imperfecta and was investigated
      for COL1A1/A2 mutations which have been proven to be negative. Autosomal
      recessive type of osteogenesis imperfecta was proposed as well, no mutations have
      been encountered. A homozygous for CTSA gene mutation, the gene associated with
      Galactosialidosis was identified via whole exome sequencing (Next-Generation
      Sequencing projects) has been identified. INTERVENTIONS: Early in her life she
      had a history of frequent fractures of the long bones since she was 4 years which
      was followed by vertebral fractures at the age of 12 years. She manifested lower
      serum 25OH-D levels and were associated with lower LS-aBMD Z-scores with higher
      urinary bone turnover indexes (urinary NTX/Cr). OUTCOMES: Lysosomal storage
      diseases (LSD) have a strong correlation with the development of osteoporosis.
      LSD causes skeletal abnormalities results from a lack of skeletal remodeling and
      ossification abnormalities owing to abnormal deposition of GAGs (impaired
      degradation of glycosaminoglycans ) in bone and cartilage. 3D reconstruction CT
      scan of the spine showed diffuse hyperostosis of almost the entire spine (begins
      at the level of T4- extending downwards to involve the whole thoraco-lumbar and
      upper part of the sacrum) with total diffuse fusion of the pedicles, the
      transverse and articular processes, the laminae and the spinous processes.
      LESSONS: This is the first clinical report of adult patient with a history of
      osteoporosis and fractures with the late diagnosis of Galactosialidosis.
      Osteogenesis imperfecta (autosomal dominant and recessive) were the first given
      diagnoses which proven negative. The pathophysiology of the spine ankylosis in
      our current patient and its correlation with LSD, antiresorptive medications,
      vitamin D3 and supplemental calcium is not fully understood. Therefore, further
      studies are needed to elucidate this sort of correlation.

PMID- 29642149
TI  - Full recovery after prolonged resuscitation from cardiac arrest due to
      propafenone intoxication: A case report.
AB  - RATIONALE: The prognosis of cardiac arrest (CA) induced by propafenone
      intoxication was thought to be very poor. The maximal duration of cardiopulmonary
      resuscitation (CPR) for propafenone induced CA is unknown. PATIENT CONCERNS: We
      describe a case that was successfully resuscitated after prolonged CPR (totaling
      340 minutes during one hospital visit) for propafenone intoxication without
      subsequent neurological sequela. DIAGNOSES: A previously healthy 36-year-old
      female who developed multiple and prolonged CAs after consuming 98 tablets of
      50mg propafenone. The CPR duration of this case, to the best of our knowledge, is
      the longest of all existing propafenone-induced CPR events to still have full
      recovery. We also analyse the contributing factors to this successful CPR.
      INTERVENTIONS: Sodium bicarbonate, inotropic drugs and pacemaker application did
      not prevent the occurrence of CA. A full recovery was eventually achieved after
      prolonged CPR with a mechanical CPR device, blood purification and other
      aggressive supportive treatments. OUTCOMES: Full recovery without neurological
      sequela. LESSONS: Prolonged CPR including the application of mechanical CPR
      devices should be considered in propafenone-related CA, especially in young
      patients without significant comorbidities and delayed resuscitation.

PMID- 29642150
TI  - The poor prognosis of the primary gastric epithelioid angiosarcoma: A case
      report.
AB  - RATIONALE: Primary gastric epithelioid angiosarcoma is a highly aggressive
      endothelial cell malignancy and may pose a great diagnostic challenge. PATIENT
      CONCERNS: Here we describe the case of a 56-year-old man presented with melena
      and epigastric dull pain for 2 weeks. DIAGNOSIS: Primary gastric epithelioid
      angiosarcomas: the definitive diagnosis was provided by immunohistochemical
      analysis with endothelial markers such as cluster of differentiation 31 (CD31),
      ether-a-go-go-related gene (ERG), and Freund leukemia integration (FLI-1).
      INTERVENTIONS: After gastroscopic biopsy was performed at the bleeding fundus and
      the results suggested malignant tumor, radical gastrectomy was performed.
      OUTCOMES: Unfortunately, regional lymph node enlargement and distant metastases
      occurred about 1 month later. The patient did not have the opportunity to undergo
      chemotherapy or other treatment and died from multiple organ dysfunction
      syndrome. LESSONS: Primary gastric epithelioid angiosarcomas are rare tumors with
      a high rate of lymph nodes and peripheral organs metastasis. The strong
      cytokeratin expression in epithelioid angiosarcomas represents a diagnostic
      pitfall for pathologists. Their clinical behaviors are unpredictable and results
      with surgical excision alone have been disappointing. Thus, the prognosis is
      generally considered poor and patients seldom can survive over 1 year after
      diagnosis.

PMID- 29642151
TI  - Risk interrelationship among multiple primary tumors: A case report and review of
      literature.
AB  - RATIONALE: Along with advanced management in oncology, great progress has been
      recently achieved in the studies of multiple primary tumors. Several reports have
      studied the coexistence between lymphoma and either renal cell carcinoma (RCC) or
      Warthin tumor. However, the level of coexistence between these cases remains
      unclear due to the absence of a distinct link between them. PATIENT CONCERNS: We
      present a unique case of multiple primary tumors (lymphoma, RCC, and Warthin
      tumor) in an 80-year-old man and a review of the literature on the coexistence of
      RCC with lymphoma and lymphoma with Warthin tumor. DIAGNOSIS: With a history of
      RCC, the patient had a freely movable lump under his left ear, and the
      pathological report indicated Hodgkin lymphoma and Warthin tumor. INTERVENTION:
      RCC and Warthin tumor of the patient were surgically treated, followed by 2
      cycles (14 days per cycle) of Epirubicin 40 mg day 1, Bleomycin 8 mg day 1,
      Vincristine 2 mg day 1, and Dacarbazine 500 mg day 1. The chemotherapy protocol
      was then changed to Epirubicin 40 mg day 1, Vincristine 2 mg day 1, and
      Dacarbazine 500 mg day 1 for 7 cycles. OUTCOMES: After the last day of
      chemotherapy, the patient showed a complete response. LESSONS: To the best of our
      knowledge, this paper is the first to report a case of multiple primary tumors
      with a complete response. For their early detection, favorable prognosis, and
      correlation identification, we suggest a transitive relation between these
      coexisting tumors. Therefore, similar studies should be conducted.

PMID- 29642152
TI  - Mandibular metastasis as the first clinical indication of occult lung
      adenocarcinoma with multiple metastases: A case report.
AB  - RATIONALE: Although metastases to the oral and maxillofacial region (OMR) are
      rare, the lung is the most common primary site metastasizing to the OMR. PATIENT
      CONCERNS: An 83-year-old woman presented with reports of trismus, occlusal
      discomfort, swelling, and spontaneous pain in the right buccal region. Despite
      the absence of abnormal chest imaging findings, immunohistochemical analysis of
      biopsy specimens of the mandible and the thyroid indicated that the patient had
      multiple metastases from a lung poorly differentiated adenocarcinoma. DIAGNOSES:
      Metastases to the OMR and the thyroid from an undiscovered lung adenocarcinoma.
      INTERVENTIONS: Gefitinib was started as first-line chemotherapy, and zoledronic
      acid was administered for bone metastases. OUTCOMES: Follow-up imaging
      examinations showed ossification and deformation of the right mandibular ramus
      and the condylar process. Although 2 years have passed since the first visit to
      our hospital, lung lesions have not been confirmed by imaging examinations.
      LESSONS: Clinicians should consider the possibility that symptoms in the OMR may
      be the first clinical sign of an undiscovered distant primary tumor, and the
      primary tumors may not be detected by imaging examinations even when metastases
      to the OMR are revealed.

PMID- 29642153
TI  - DRESS syndrome with thrombotic microangiopathy revealing a Noonan syndrome: Case
      report.
AB  - RATIONALE: The life-threatening drug rash with eosinophilia and systemic symptoms
      (DRESS) syndrome occurs most commonly after exposure to drugs, clinical features
      mimic those found with other serious systemic disorders. It is rarely associated
      with thrombotic microangiopathy. PATIENT CONCERNS: We describe the unique case of
      a 44-year-old man who simultaneously experienced DRESS syndrome with thrombotic
      microangiopathy (TMA) after a 5 days treatment with fluindione. DIAGNOSES:
      Clinical evaluation leads to the discovery of an underlying lymphangiomatosis,
      due to a Noonan syndrome. INTERVETIONS: The anticoagulant was withdrawn, and
      corticosteroids (1 mg/kg/day) and acenocoumarol were started. OUTCOMES: Clinical
      improvement ensued. At follow-up the patient is well. LESSONS: The association of
      DRESS with TMA is a rare condition; we believe that the presence of the
      underlying Noonan syndrome could have been the trigger. Moreover, we speculate
      about the potential interrelations between these entities.

PMID- 29642154
TI  - Quantitative comorbidity risk assessment of dementia in Taiwan: A population
      based cohort study.
AB  - Dementia is one of the most burdensome illnesses in elderly populations
      worldwide. However, the literature about multiple risk factors for dementia is
      scant.To develop a simple, rapid, and appropriate predictive tool for the
      clinical quantitative assessment of multiple risk factors for dementia.A
      population-based cohort study.Based on the Taiwan National Health Insurance
      Research Database, participants first diagnosed with dementia from 2000 to 2009
      and aged >=65 years in 2000 were included.A logistic regression model with
      Bayesian supervised learning inference was implemented to evaluate the
      quantitative effects of 1- to 6-comorbidity risk factors for dementia in the
      elderly Taiwanese population: depression, vascular disease, severe head injury,
      hearing loss, diabetes mellitus (DM), and senile cataract, identified from a
      nationwide longitudinal population-based database.This study enrolled 4749 (9.5%)
      patients first diagnosed as having dementia. Aged, female, urban residence, and
      low income were found as independent sociodemographic risk factors for dementia.
      Among all odds ratios (ORs) of 2-comorbidity risk factors for dementia, comorbid
      depression and vascular disease had the highest adjusted OR of 6.726. The 5
      comorbidity risk factors, namely depression, vascular disease, severe head
      injury, hearing loss, and DM, exhibited the highest OR of 8.767. Overall, the
      quantitative effects of 2 to 6 comorbidities and age difference on dementia
      gradually increased; hence, their ORs were less than additive. These results
      indicate that depression is a key comorbidity risk factor for dementia.The
      present findings suggest that physicians should pay more attention to the role of
      depression in dementia development. Depression is a key cormorbidity risk factor
      for dementia. It is the urgency of evaluating the nature of the link between
      depression and dementia; and further testing what extent controlling depression
      could effectively lead to the prevention of dementia.

PMID- 29642155
TI  - Occipital epilepsy versus progressive myoclonic epilepsy in a patient with
      continuous occipital spikes and photosensitivity in electroencephalogram: A case
      report.
AB  - INTRODUCTION: Progressive myoclonic epilepsy (PME) is rare epilepsy syndrome.
      Although EEG is a useful neurophysiological technique in the evaluation of
      epilepsy, few EEG abnormalities have been described in PME. So, how to use EEG
      hints to establish the suspected diagnosis of PME as soon as possible should be
      addressed. CASE PRESENT: We presented a case with refractory myoclonic seizures,
      and progressive neurological deterioration, diagnosed as PME and neuronal ceroid
      lipofuscinosis disease by gene testing. The patient manifested with a significant
      regression in her speech ability and motor balance. The mini-mental state
      examination showed poor scores of 15/30. The magnetic resonance imaging showed
      diffused atrophy. Her EEG showed slow background with continuous occipital small
      spikes and photosensitivity. The following genetic testing with mutation in CLN6
      confirmed the diagnosis and excluded the occipital epilepsy. CONCLUSION: Our case
      showed rare manifestations and special EEG features of PME, which may be confused
      with occipital epilepsy or photosensitive epilepsy. Thus, if the continuous
      occipital spikes and photosensitivity were presented in a patient with refractory
      seizures and developmental regression, PME should be considered.

PMID- 29642156
TI  - Neurolymphomatosis in non-Hodgkin lymphoma with cranial multineuritis: A case
      report.
AB  - RATIONALE: Neurolymphomatosis (NL) is a rare syndrome of lymphoma and leukemic
      infiltration of cranial or peripheral nerves. PATIENT CONCERNS: We report a case
      of non-Hodgkin Lymphoma (NHL) in a 24-year-old man presented with difficulty in
      swallowing, hypersalivation, hoarseness, ptosis, facial paralysis, and facial
      hypoesthesia associated with NL. DIAGNOSIS: NL was diagnosed based upon cranial
      magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) examination.
      INTERVENTIONS: The patient was treated with intrathecal methotreaxate (12.5 mg)
      and cytosine arabinoside (70 mg), systemic high-dose methotrexate therapy, and
      cranial radiotherapy. OUTCOME: Due to the deterioration of general condition of
      the patient, he was admitted to intensive care unit, but died 22 days after the
      onset of symptoms in spite of aggressive treatment. LESSONS: In this case, we
      present a patient with T cell lymphoma and multineuritis of NL diagnosed by MRI
      and as far as we know, this is the first reported case in which so many cranial
      nerves (3, 5, 7, 8, 9, and 10 th) were involved. Briefly, in a patient with
      hematologic malignancy and neurological complaints, NL should be considered.
      Early and effective use of imaging modalities such as positron emission
      tomography (PET-CT), MRI, and aggressive therapies are important for prolonged
      survival.

PMID- 29642157
TI  - A successful treatment of necrotizing fasciitis following the surgery of distal
      radius plate removal: A case report and literature review.
AB  - RATIONALE: Necrotizing fasciitis (NF) is defined as a rare, rapidly progressive,
      and highly lethal skin infection characterized by necrosis of the fascia and
      subcutaneous tissue. PATIENT CONCERNS: The present study aims to discuss the case
      of a 35-year-old man who developed NF following a routine sterile right distal
      radius bone plate removal surgery. DIAGNOSES: The patient was suspected of NF
      based on his clinical manifestations, laboratory tests, and imaging results. The
      diagnosis of NF was confirmed by histological examinations. INTERVENTIONS: Serial
      prompt and extensive debridement was performed during the rapid and aggressive
      extension of the skin infection, together with antibiotics and supportive
      treatments. OUTCOMES: The condition of the patient finally improved on the sixth
      day of disease progression. Skin grafting of his right forearm wound was
      performed successfully 2 months after the admission. LESSONS: NF can occur during
      the perioperative period for routine clean radius plate removal operation in
      patients with no risk factor for NF. The objective is to remind the physicians to
      stay aware of this disease, especially its early clinical signs and symptoms.
      Urgent subsequent treatment, including surgical debridement, antibiotic therapy,
      and supporting management, is the key to ensure the survival and better prognosis
      of patients.

PMID- 29642158
TI  - Primary epithelioid angiosarcoma of right hip joint: A case report and literature
      review.
AB  - RATIONALE: Epithelioid angiosarcoma (EA) is a rare, highly invasive tumor. The
      histopathological features of EA are not distinct and less reported in the
      literature, and most of the medical records are incomplete. PATIENT CONCERNS: A
      61-year-old woman who came to the hospital because of pain in her right hip. This
      patient had had surgery for right hip tuberculosis 30 years ago. DIAGNOSES: The
      present study reports a case of primary EA of bone with aneurysmal bone cyst
      (ABC) that was diagnosed by 3 experienced pathologists. INTERVENTIONS: The
      patients had undergone 2 surgeries; however, an early recurrence of the tumor was
      caused the death of the patient. OUTCOMES: Ten EA cases from other literature
      were reviewed in this article; all the symptoms were found in different parts of
      bone, and the case data were relatively complete. The primary clinical features
      and nonspecific histopathological morphology of the disease were summarized from
      the 11 cases mentioned in the literature, and the main immunohistochemistry
      characteristics and diagnostic traps of EA were reviewed. LESSONS: Because the
      tumor has no characteristic diagnostic index in imaging and laboratory
      examination, the histopathologic features are not typical, especially in the case
      of obvious secondary lesions. It is easy to miss and misdiagnose. If possible,
      the diagnosis should be combined with immunohistochemical results.

PMID- 29642159
TI  - Multiple total hip arthroplasties in refractory immune thrombocytopenic purpura:
      A case report and literature review.
AB  - RATIONALE: Refractory immune thrombocytopenic purpura (RITP) manifests as low
      platelet count, with a high risk of hemorrhage, treatment difficulty, and high
      mortality. Total hip arthroplasty (THA) in RITP is rarely reported. This study
      aimed to evaluate multiple THAs or revision total hip arthroplasties (RTHAs) in
      RITP. PATIENT CONCERNS: The male patient with RITP was 54-year-old patient and
      hospitalized on September 21, 2009, with the main complaint of bilateral hip pain
      after traveling for 2 weeks. The patient had a history of ITP for 16-years, with
      no response to hormone therapy (after adequate hormone therapy, platelet count
      persistently remained below 30 * 10/L). Two year prior to visit, the patient
      underwent splenectomy, and postoperative platelet persistently fluctuated around
      10 to 20 * 10/L. The patient did not undergo regular reexaminations, and declined
      immunosuppressants. DIAGNOSES: Femoral neck fracture; Refractory immune
      thrombocytopenic purpura (RITP). INTERVENTIONS: A RITP patient with femoral neck
      fracture received 2 THAs and 1 RTHA. First THA indication was significant left
      dislocation of Garden III type. RTHA was performed following prosthetic loosening
      after left total hip arthroplasty. The second THA was prompted by non-healing of
      the old fracture, significant pain, and a low Harris score. Platelet count
      remained <20 * 10/L, and conventional drugs, splenectomy, and platelet
      transfusion had no effects. A large gamma-globulin dose was administered
      preoperatively. When platelet increased to 75 * 10/L, 2 THAs and 1 RTHA were
      successfully completed. OUTCOMES: Postsurgery, conventional management was
      applied; no severe complications occurred. The wound was well healed, with
      platelet count reduced to <15 * 10/L at hospital discharge. The patient
      recovered, with a Harris score >80 at 1 year postsurgery. LESSONS: Extremely low
      platelet count is a contraindication of surgery. In this patient, preoperative
      platelet count was <100 * 10/L. Extended disease course and multiple operations
      lowered platelet count, and increased risk in surgery. However, high
      postoperative gamma-globulin dose impacted therapy, and all surgeries were
      successful, with no severe complications. The wound healed well, and the quality
      of life was significantly improved, demonstrating the feasibility and safety of
      this surgery. Multiple THA or RTHA surgeries are feasible and safe for RITP
      patients.

PMID- 29642160
TI  - A novel technique of using a miniature plate in combination with tension band
      wiring to treat comminuted patellar fractures.
AB  - Traditionally, tension band fixation has been used for treating simple fracture
      patterns; however, fixation remains a challenge, especially for comminuted
      fractures. We describe a new method of operation using a combination of a
      miniature plate with tension band wiring to treat comminuted patellar fractures.
      The aim of this technique is to transform complicate fractures into simple
      transverse fractures. As far as we know, no studies using a similar method have
      been found.The purpose of this study was to assess the effectiveness of a novel
      technique in which a miniature plate is used in combination with tension band
      wiring to treat comminuted patellar fractures.Between March 2013 and May 2015, 16
      patients with closed, displaced, comminuted fractures of the patella were
      included in the present study. All subjects underwent fixation using a
      combination of a miniature plate with a tension band wire. Knee function and
      patient status were evaluated at 12 months using the Bostman knee score and
      Lysholm knee scale.The average follow-up period was 15.6 months (range, 12-20
      months). At the 12-month follow-up, bone healing was satisfactory in all
      patients. The average postoperative Lysholm score was 91.6 +/- 1.4 (range, 84
      97). The average postoperative Bostman scale score was 26.4 +/- 0.5 (range, 22
      30), thereby indicating excellent results in 4 patients and good results in 12.
      No patients required reoperation.The results demonstrate that this new technique
      is an effective and safe treatment option for comminuted patella fractures, as it
      is associated with good clinical outcomes.

PMID- 29642161
TI  - Icotinib and whole-brain radiotherapy for the treatment in patients with brain
      metastases from EGFR-mutant nonsmall cell lung cancer: A retrospective study.
AB  - This study aimed to explore the effect and toxicity of icotinib and whole-brain
      radiotherapy (IWBRT) for the treatment of brain metastases from nonsmall cell
      lung cancer (BMNSCLC) with epidermal growth factor receptor (EGFR)-mutant among
      Chinese Han population.A total of 55 patients with EGFR-mutant BMNSCLC were
      included. They received orally icotinib (125 mg/tablet, 125 mg each time, 3 times
      daily) until disease progression. In addition, they also underwent whole-brain
      radiotherapy (3-Gy fractions once daily, 5 days weekly for a total dose of 30 Gy)
      in an attempt to extend their survival time. The outcomes consisted of complete
      response (CR), partial response (PR), stable disease (SD), progress disease (PD),
      overall response rate (ORR), progression-free survival (PFS), and overall
      survival (OS). In addition, toxicity was also recorded in this study.The CR, PR,
      SD, PD, ORR, PFS, and OS were 38.2%, 52.8%, 5.4%, 3.6%, 90.1%, 12.5%, and 48.0%
      months, respectively. In addition, mild toxicity was observed in this study.This
      study demonstrated that IWBRT is efficacious with acceptable toxicity for
      patients with EGFR-mutant BMNSCLC among Chinese Han population.

PMID- 29642163
TI  - Basal ganglia calcification and novel compound heterozygous mutations in the
      PANK2 gene in a Chinese boy with classic Pantothenate kinase-associated
      neurodegeneration: A case report.
AB  - RATIONALE: Pantothenate kinase-associated neurodegeneration (PKAN) represents an
      autosomal recessive hereditary disease. In this report, a PANK2 gene mutation in
      a Chinese child was identified, as well as detections of PKAN among his family
      members. Our findings exposed a world-wide novel compound heterozygous mutation.
      PATIENT CONCERNS: We described a 6-year-old male patient with PKAN, exhibiting
      involuntary movement for a period of 1.5 years, as well as feeding difficulties
      for 2 weeks. DIAGNOSIS: Due to brain computed tomography and magnetic resonance
      imaging results, and patient behavior, the attending physician suspected a
      hereditary effect. INTERVENTIONS: The patient sample underwent high-throughput
      sequencing. Subsequently, his parents and sister were screened for the mutations
      identified in the patient genome. OUTCOMES: High-throughput sequencing revealed a
      novel complex heterozygous mutation of the PANK2 gene, which was detected in the
      second and fourth exons, c.A650G, and c.T1341G, respectively, resulting in amino
      acid alterations (p.D217G and p.D447E, respectively). The child's father was
      confirmed to possess a heterozygous c.A650G mutation, while his mother was
      heterozygous for the c.T1341G mutation. LESSONS: The key finding of the study
      encompassed the detection of a novel PANK2 gene mutation in a child of Chinese
      ethnicity with PKAN. The PANK2 gene c.A650G, as well as c.T1341G, mutations may
      be potential mutation hotspots in children with PKAN in Mainland China.

PMID- 29642162
TI  - Stapled side-to-side anastomosis might be benefit in intestinal resection for
      Crohn's disease: A systematic review and network meta-analysis.
AB  - BACKGROUND AND AIM: Intestinal anastomosis is an essential step in the intestinal
      resection in patients with Crohn's disease (CD). Anastomotic configuration such
      as handsewn end-to-end anastomosis (HEEA), stapled side-to-side anastomosis
      (SSSA) and so on may be a predictor of prognosis for postoperative CD patients.
      However, the association between anastomotic types and surgical outcomes are
      controversial. The aim of this review is to identify the optimal anastomosis for
      intestinal resection in patients with CD. METHODS: Clinical trials comparing
      anastomosis after intestinal resection in patients with CD were searched in the
      database of MEDLINE, EMBASE, and the Cochrane Library. Outcomes such as
      postoperative hospital stay, complications, mortality, recurrence, and
      reoperation were evaluated. Pairwise treatment effects were estimated through a
      random-effects network meta-analysis based on the frequency framework by using
      the STATA software and reported as the estimated summary effect for each
      comparison between the 2 treatments in the network with a 95% credible interval.
      RESULTS: A total of 1113 patients in 11 trials were included. In pair-wise
      comparisons between groups, for overall postoperative complications, SSSA showed
      a more probability of superiority to HEEA; for complications other than
      anastomotic leak, anastomotic leak, wound infection, postoperative hospital stay
      and mortality, there were no significant difference between groups; for clinical
      recurrence, SSSA showed a more probability of superiority to HEEA; for
      reoperation, SSSA showed a more probability of superiority to HEEA. The number of
      eligible randomized controlled trails (RCTs) was small, and more than half of the
      included trials were retrospective studies; selection bias may lead to a less
      power in this assessment; follow-up time between different groups was different,
      which may possibly have affected the interpretation of the analysis of long-term
      outcome. CONCLUSION: By comprehensive analyzing all the postoperative outcomes,
      SSSA appeared to be the optimal anastomotic strategy after intestinal resection
      for patients with CD.

PMID- 29642164
TI  - Hydroa vacciniforme-like cutaneous T-cell lymphoma in a child: A case report.
AB  - RATIONALE: Hydroa vacciniforme (HV)-like T-cell lymphoma is a rare malignancy in
      childhood associated with Epstein-Barr virus infection. PATIENT CONCERNS: A 6
      year old girl presented with complaint of 3-year history of recurrent skin
      lesions, 3 months of fever accompanied by cough for 8 days. DIAGNOSES: Skin
      biopsy revealed a HV-like lymphoma presentation and positive signals of EBER were
      detected by in situ hybridization. TCR-gamma gene monoclonal rearrangement was
      present. A HV-like cutaneous T-cell lymphoma was diagnosed. INTERVENTIONS: The
      girl was treated with cyclosporine and CHOP. OUTCOMES: The girl's condition had
      been stable for 6 months. LESSONS: Our case highlights the necessity for taking
      the HV-like lymphoma as a differential diagnosis especially when a patient
      manifests as recurrent skin lesions accompanied by systemic involvement.

PMID- 29642165
TI  - Glial alterations in human prion diseases: A correlative study of astroglia,
      reactive microglia, protein deposition, and neuropathological lesions.
AB  - BACKGROUND: Neuroinflammation has recently been proposed to be a major component
      of neurodegenerative diseases. The aim of this study was to determine how the
      interaction between microglia and astroglia, which are the primary immune cell
      populations in the brain, and pathological prion protein (PrPsc) could influence
      the development and propagation of this neurodegenerative disease. Because a
      relevant role for glial response in prion disease has been clearly demonstrated
      in our previous studies using the natural animal model, a similar approach has
      been taken here using the natural human model. METHODS: A morphological approach
      has been developed to analyze cerebellar samples from patients with Creutzfeldt
      Jakob disease (CJD) in comparison with healthy control cases. Histopathological
      lesions were assessed, and PrPsc, glial fibrillary acidic protein (GFAP) and
      reactive microglia were immunolabelled by specific antibodies. Furthermore, co
      location studies using confocal microscopy were performed to determine the
      possible relationships between both types of glial cells in all samples. RESULTS:
      The results presented in this study support the involvement of both types of
      glial cells in CJD. Evidence of increased astrocyte and microglia reactivity can
      be observed in all CJD cases, and a close relationship between the types of glia
      is demonstrated by co-location studies. CONCLUSION: Proteinopathies such as
      Alzheimer, Parkinson, and Huntington diseases, where aberrant proteins spread
      throughout the brain during disease progression, may share a molecular basis and
      mechanisms of propagation. Therefore, studies elucidating the interaction between
      gliosis and prion propagation may be relevant to these other neurodegenerative
      diseases and may provide new targets for therapeutic intervention.

PMID- 29642166
TI  - An investigation into psychological stress and its determinants in Xinjiang
      desert oil workers.
AB  - The present study aims to investigate psychological stress and its determinants
      in Xinjiang field oil workers. Specifically, we aim to elucidate the mechanisms
      underlying psychological stress by comprehensively and quantitatively evaluating
      the processes involved in psychological stress, the factors which influence it,
      and their relationship.The participants were 1200 field oil workers in Xinjiang
      who had been in service for at least 1 year. A structural equation model based on
      data from the symptom checklist, social support research scale, personality
      questionnaire, occupational burnout questionnaire, and occupational stress
      questionnaire was constructed to investigate the social (environmental) factors
      that influence physiological stress and the interplay among these factors.The
      positive incidence of psychological stress in the field oil workers in Xinjiang
      was 12.54%. The structural equation model indicated that the main factors that
      influenced psychological stress in these workers included social support (0.077),
      occupational role (0.165), personal strain response (0.139), personality (0.189),
      and occupational burnout (0.380). Among these factors, occupational role,
      personality, and occupational burnout had a relatively strong predictive power
      for psychological stress reactions. The cortisol level in workers with positive
      psychological stress was significantly higher than that in workers with negative
      psychological stress.Occupational stress, personality, and occupational burnout
      exert an impact on psychological stress in field oil workers. Therefore,
      interventions to address these factors should be taken to reduce the incidence of
      psychological stress.

PMID- 29642167
TI  - Burnout and study engagement among medical students at Sun Yat-sen University,
      China: A cross-sectional study.
AB  - This study aims to investigate burnout and study engagement among medical
      students at Sun Yat-sen University, China.A cross-sectional survey was conducted
      among undergraduate medical students of Sun Yat-sen University, China. A total of
      453 undergraduate students completed a self-administered, structured
      questionnaire between January and February, 2016. Burnout and study engagement
      were measured using the Maslach Burnout Inventory-Student Survey (MBI-SS) and the
      UTRECHT Work Engagement Scale-Students (UWES-S), respectively. Subjects who
      scored high in emotional exhaustion subscale, high in cynicism subscale, and low
      in professional efficacy subscale simultaneously were graded as having high risk
      of burnout. Independent sample t tests and chi-square tests were used to compare
      the differences in burnout and work engagement between genders, majors, and grade
      levels.The means (standard deviations) of the MBI-SS subscales were 3.42 (1.45)
      for emotional exhaustion, 2.34 (1.64) for cynicism, and 3.04 (1.30) for
      professional efficacy. The means (standard deviations) of the UWES-S subscales
      were 3.13 (1.49) for vigor, 3.44 (1.47) for dedication and 3.00 (1.51) for
      absorption. Approximately 1 in 11 students experienced a high risk of burnout.
      There were no statistically significant gender differences in burnout and study
      engagement. There were also no statistically significant differences in burnout
      and study engagement subscales according to student major. Students in higher
      grades displayed increased burnout risk, higher mean burnout subscale score of
      cynicism, lower mean burnout subscale score of professional efficacy, and
      decreased mean study engagement subscale scores of dedication and absorption.
      There were strong correlations within study engagement subscales.Chinese medical
      students in this university experience a high level of burnout. Students at
      higher-grade level experience more burnout and decreased study engagement
      compared with students in lower level.

PMID- 29642168
TI  - Spontaneous bilateral subclavian vein thrombosis in a 40-year-old man: A case
      report.
AB  - RATIONALE: Paget-Schroetter syndrome (PSS) is an uncommon condition that refers
      to primary (spontaneous) thrombosis of the deep veins that drain the upper
      extremities because of anatomical anomalies or repetitive strenuous arm activity.
      Bilateral spontaneous upper extremity deep-vein thrombosis (UEDVT) is an
      extremely rare phenomenon in adults, which may be misdiagnosed by physicians in
      acute settings. PATIENT CONCERNS: A 40-year-old man presented to our emergency
      department because of progressive left upper arm swelling for 1 day. He denied
      fever, chest pain, dyspnea, trauma, or any other systemic disease before. The
      swollen left arm also had no local heat or redness with normal radius pulsation.
      He was a laborer who lifted heavy objects. DIAGNOSES: Blood examination included
      tests for complete blood count, renal function, liver function, blood coagulation
      profile, cardiac enzyme levels, and D-dimer level. Results showed that the white
      blood cell count, renal and liver functions, and cardiac enzyme levels were all
      within their normal ranges, except for the elevated D-dimer level (1.93 mg/L).
      Chest radiography and electrocardiography were performed with nonspecific
      findings. Subsequently, computed tomographic angiography was recommended for the
      suspected deep-vein thrombosis. The report showed venous thrombosis involving the
      bilateral subclavian and internal jugular veins. INTERVENTIONS: Heparin and
      enoxaparin were prescribed for this patient, with loading and maintenance doses.
      He was then admitted to our cardiovascular ward for further treatment. OUTCOMES:
      The patient was discharged 9 days later in a stable condition. LESSONS: Emergency
      physicians should consider the rare condition of UEDVT when a healthy patient
      presents with acute arm swelling. Patient history taking should be thorough,
      especially concerning the risk factors of secondary causes and possible frequent
      vigorous heavy lifting and overhead motion. Without secondary risk factors,
      primary upper deep-vein thrombosis might be suspected. Further laboratory tests
      and imaging studies, especially bilateral imaging, should be arranged to exclude
      secondary causes and to confirm the diagnosis.

PMID- 29642169
TI  - Cost-effectiveness and short-term clinical outcomes of argon plasma coagulation
      compared with endoscopic submucosal dissection in the treatment of gastric low
      grade dysplasia.
AB  - Endoscopic treatment such as endoscopic submucosal dissection (ESD) or argon
      plasma coagulation (APC) is widely performed to treat gastric low-grade dysplasia
      (LGD). We aimed to evaluate the clinical efficacy of APC versus ESD for gastric
      LGD in terms of cost-effectiveness. This was a retrospective review of patients
      with gastric LGD who were treated with endoscopic intervention (APC or ESD)
      between March 2011 to December 2015. Fifty-nine patients treated with APC and 124
      patients treated with ESD were included. Patients in the APC group were
      significantly older (mean age, 67.68 vs 63.90 years, respectively, P < .01), had
      an increased rate of Helicobacter pylori infection (27.1 vs 10.5%, respectively,
      P < .01), and had a higher mean Charlson Comorbidity Index score (2.32 vs 0.38,
      respectively, P < .01) than those in the ESD group. The 2 groups did not differ
      in tumor size, location, macroscopic morphology, or surface configuration. The
      procedure time (11.31 vs56.44 minutes, respectively, P < .01), and hospital stay
      (3.2 vs 5.6 days, respectively, P < .01) were significantly, shorter in the APC
      group than in the ESD group. Additionally, the cost incurred was significantly,
      lower in the APC group than in the ESD group (962.03 vs 2,534.80 dollars,
      respectively, P < .01). APC has many advantages related to safety, and cost
      effectiveness compared with ESD. Therefore, APC can be considered an alternative
      treatment option for gastric LGD.

PMID- 29642170
TI  - A case of adult onset Still's disease with mutations of the MEFV gene who is
      partially responsive to colchicine.
AB  - RATIONALE: Familial Mediterranean fever (FMF) and adult onset Still's disease
      (AOSD) have overlapping features, and are categorized as being on the spectrum of
      autoinflammatory diseases (AIDs). FMF is more prevalent in the Mediterranean
      region but rarely, described in the Chinese population. PATIENT CONCERNS: We
      present an interesting case of a Han Chinese AOSD patient with episodic fever,
      wheals, and polyarthritis for 2 years. DIAGNOSIS: Sequencing analysis found exon
      2 mutations of the MEFV gene (c.329T>C [L110P], and c.442G>C [E148Q]).
      INTERVENTION: Her arthritis was well-controlled with colchicine treatment, but
      fever, and rashes were not. OUTCOMES: She eventually received tocilizumab, in
      addition to colchicine, and her symptoms completely disappeared. LESSONS: MEFV
      mutations may exist in AOSD patients, and treatment with colchicine might be
      helpful in such patients.

PMID- 29642171
TI  - Over-the-counter analgesic powder use in patients presenting with intracerebral
      hemorrhage: A case series.
AB  - INTRODUCTION: Over-the-counter (OTC) analgesics including aspirin-containing
      powder formulations (BC Powder, Goody's Powder) (ACPFs) are commonly utilized in
      the United States. While the ACPFs have been associated with upper
      gastrointestinal bleeding, we describe a case series of patients presenting with
      intracerebral hemorrhage (ICH) within 24 hours of ingestion. METHODS: We reviewed
      all ICH patients presenting to a comprehensive stroke center from September 1,
      2014 through June 30, 2016 to identify patients who reported taking BC Powder or
      Goody's Powder within 7 days of their stroke. Baseline characteristics,
      medication use, stroke risk factors, clinical imaging, and laboratory testing
      were reviewed retrospectively. RESULTS: Of 334 patients admitted with ICH during
      the study period, 6 (2%) reported use of OTC analgesic powders within 1 week of
      their index stroke. All had consumed at least 1 packet within 24 hours of their
      ICH. All patients were African American and all except 1 patient were females.
      Three patients had no identified traditional stroke risk factors and 3 other
      patients had evidence of mild hypertension history. CONCLUSIONS: Over-the-counter
      analgesic powders containing high doses of aspirin including BC Powder and
      Goody's Powder may contribute to ICH in patients with no or minimal risk factors.
      Providers should inquire about the use of these powders in ICH patients
      particularly among African Americans.

PMID- 29642172
TI  - A case report of symptomatic presacral myelolipoma.
AB  - RATIONALE: Extra-adrenal myelolipoma in the presacral area often raises a concern
      for liposarcoma because they have similar radiologic features. PATIENT CONCERNS:
      A 70-year-old woman with multiple abdominal surgeries in the past presented with
      persistent lower abdominal pain and anemia. A presacral mass, found on a pelvic
      magnetic resonance image (MRI), was suspicious of liposarcoma, as it is the most
      common fat containing mass in the presacral area. It is often difficult to make a
      diagnosis of myelolipoma just based on the radiological studies, which
      necessitates a histopathologic examination of the resected mass for a definitive
      diagnosis. DIAGNOSES: Myelolipoma is an encapsulated, benign tumor containing
      mature adipocytes and hematologic cells. Most of the patients with myelolipoma
      remain asymptomatic but continued growth of tumor without local invasion can lead
      to compression of nearby structures, causing persistent pain. INTERVENTIONS:
      Asymptomatic patients do not require intervention but surgical resection is
      indicated for persistent pain or hemorrhage inside the tumor. Our patient had 2
      indications for surgery - persistent pain as well as a provisional diagnosis of
      liposarcoma. After the surgical resection, pelvic pain was resolved, and a
      diagnosis of myelolipoma was made based on histopathologic examination. OUTCOMES:
      Patient was reassured that it was myelolipoma, a benign tumor, not requiring
      subsequent surveillance for recurrence. LESSONS: Despite advancement in imaging
      techniques, and knowledge of the radiological features of myelolipoma, it still
      remains as a challenge for clinicians to make the distinction between liposarcoma
      and myelolipoma only based on diagnostic radiology. Although myelolipoma is a
      benign tumor, if patient suffers from persistent pain due to local mass effect,
      surgical resection is required.

PMID- 29642173
TI  - Fulminant course in a patient with anti-N-methyl-D-aspartate receptor
      encephalitis with bilateral ovarian teratomas: A case report and literature
      review.
AB  - RATIONALE: Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is an
      autoimmune disorder that can be controlled and reversed by immunotherapy. The
      presentation of NMDA receptor encephalitis varies, but NMDA receptor encephalitis
      is seldom reported in patients with both bilateral teratomas and preexisting
      brain injury. PATIENT CONCERNS: A 28-year-old female with a history of traumatic
      intracranial hemorrhage presented acute psychosis, seizure, involuntary movement,
      and conscious disturbance with a fulminant course. Anti-NMDA receptor antibody
      was identified in both serum and cerebrospinal fluid, confirming the diagnosis of
      anti-NMDA receptor encephalitis. Bilateral teratomas were also identified during
      tumor survey. DIAGNOSES:: anti-N-methyl-D-aspartate receptor encephalitis.
      INTERVENTIONS: Tumor resection and immunotherapy were performed early during the
      course. OUTCOMES: The patient responded well to tumor resection and
      immunotherapy. Compared with other reports in the literature, her symptoms
      rapidly improved without further relapse. LESSONS: This case report demonstrates
      that bilateral teratomas may be related to high anybody titers and that the
      preexisting head injury may be responsible for lowering the threshold of
      neurological deficits. Early diagnosis and therapy are crucial for a good
      prognosis in such patients.

PMID- 29642174
TI  - Acquired diaphragmatic hernia in pediatrics after living donor liver
      transplantation: Three cases report and review of literature.
AB  - RATIONALE: Diaphragmatic hernia (DH) in pediatrics following living donor liver
      transplantation (LDLT) has been seldom reported in the past. PATIENT CONCERNS: We
      report successful diagnosis and treatment of three pediatric cases with DH
      secondary to LDLT, discuss the possible etiology, and review the relevant
      literature. DIAGNOSES: The primary disease was biliary atresia and DH was
      diagnosed by computed tomography scan or x-ray of chest. INTERVENTIONS:
      Laparotomy was performed successfully to repair the DH. OUTCOMES: The respiratory
      and digestive function was gradually recovered in 1 to 2 weeks after repair
      operation. In 2 to 8 months follow-up, patients were asymptomatic without any
      respiratory or digestive complications. LESSONS: DH post-LDLT should be
      recognized as a possible complication when a left lateral segment graft is used.
      Careful clinical examination and prompt surgery could minimize complications.

PMID- 29642175
TI  - Apatinib + CPT-11 + S-1 for treatment of refractory brain metastases in patient
      with triple-negative breast cancer: Case report and literature review.
AB  - RATIONALE: Brain metastasis (BM) is a rising challenge in forward-looking
      oncology, as its treatment choices are very limited, especially, after the
      failure of local treatment schemes. PATIENT CONCERNS: We report on a 39-year-old
      Chinese woman who was diagnosed with stage IV triple-negative breast cancer(TNBC)
      with multiple brain, lung, and bone metastases. She had previously, undergone
      whole-brain radiation therapy. Paclitaxel, platinum, UTD1, capecitabine,
      gemcitabine, vinorelbine, and single-agent apatinib were then administered as
      first- to fifth-line therapies. She exhibited progression each time after a short
      period of disease stabilization. DIAGNOSES: Triple-negative breast cancer.
      INTERVENTIONS: The patient chose treatment with apatinib+CPT-11+S-1 as the sixth
      line therapy. OUTCOMES: A remarkable response of the brain, and lung metastases,
      and alleviation of the brain edema were achieved, and these effects persisted for
      7 months. LESSONS: We describe the significant anti-tumor effect of apatinib +
      CPT-11 + S-1 against BMs from breast cancer. This report is the first to suggest
      potential approaches to BM treatment using this scheme and describes the effects
      of an apatinib-containing regimen on BMs.

PMID- 29642176
TI  - The anatomical and imaging study of pes anserinus and its clinical application.
AB  - BACKGROUND: The pes anserinus was an important graft choice for anterior cruciate
      ligament (ACL) reconstruction. The infrapatellar branch of the saphenous nerve
      (IPBSN) might be damaged in this surgery. This study aimed to provide anatomic
      and ultrasonic measurement data of pes anserinus and superficial nerves. METHODS:
      Eighty lower limb specimens of forty adult cadavers were dissected. The length,
      width, thickness, and the position of the tibial attachment of pes anserinus
      tendons were anthropometric measured, as well as the distance between the
      infrapatellar branch of the saphenous nerve and the pes anserinus. Sixty healthy
      adult participants were enrolled for ultrasonic research. The length, width,
      thickness of pes anserinus was also measured and the saphenous nerve was also
      assessed. RESULTS: Anatomic results showed that there were 3 types of pes
      anserinus, the infrapatellar branch of the saphenous nerve (IPBSN) was almost
      paralleled to the upper edge of the pes anserinus tendon, and the average of
      distance between them was about 0.95 cm. The length of semitendinosus and
      gracilis tendons were 146.49 +/- 12.83 mm and 124.62 +/- 8.86 mm, the width of
      sartorius tendon was 25.58 +/- 4.65 mm, wider than other tendons. The
      classification of pes anserinus tendons and the saphenous nerves could be
      identified in ultrasonic image. The length of semitendinosus and gracilis tendons
      were 151.35 +/- 9.65 mm and 120.86 +/- 8.99 mm, the width of sartorius tendon was
      22.84 +/- 3.83 mm. And there was no significance difference between anatomic and
      ultrasonic measurement (P > .05). CONCLUSION: The morphology of pes anserinus and
      its peripheral structures could be identified and measured precisely by
      ultrasound device, a presurgical ultrasonic examination was recommended. The
      arrangement of pes anserinus tendons was classified into 3 types according to our
      results. The incision should be performed medial to tibial eminence 1.5 cm and
      under the tibial tubercle level 2 to 3 cm, an oblique incision formed an angle of
      50 degrees  with tibial transection was recommend, which was parallel to the
      direction of pes anserinus tendon.

PMID- 29642177
TI  - Companied P16 genetic and protein status together providing useful information on
      the clinical outcome of urinary bladder cancer.
AB  - SPEC P16/CEN3/7/17 Probe fluorescence-in-situ-hybridization (FISH) has become the
      most sensitive method in indentifying the urothelial tumors and loss of P16 has
      often been identified in low-grade urothelial lesions; however, little is known
      about the significations of other P16 genetic status (normal and amplification)
      in bladder cancer.We detected P16 gene status by FISH in 259 urine samples and
      divided these samples into 3 groups: 1, normal P16; 2, loss of P16; and 3,
      amplified P16. Meanwhile, p16 protein expression was measured by
      immunocytochemistry and we characterized the clinicopathologic features of cases
      with P16 gene status.Loss of P16 occurred in 26.2%, P16 amplification occurred in
      41.3% and P16 gene normal occurred in 32.4% of all cases. P16 genetic status was
      significantly associated with tumor grade and primary tumor status (P = .008 and
      .017), but not with pathological tumor stage, overall survival, and p16 protein
      expression. However, P16 gene amplification accompanied protein high-expression
      has shorter overall survival compared with the overall patients (P = .023), and
      P16 gene loss accompanied loss of protein also had the tendency to predict bad
      prognosis (P = .067).Studies show that the genetic status of P16 has a close
      relation with the stages of bladder cancer. Loss of P16 is associated with low
      grade urothelial malignancy while amplified P16 donotes high-grade. Neither P16
      gene status nor p16 protein expression alone is an independent predictor of
      urothelial bladder carcinoma, but combine gene and protein status together
      providing useful information on the clinical outcome of these patients.

PMID- 29642178
TI  - Circulating LECT2 levels in newly diagnosed type 2 diabetes mellitus and their
      association with metabolic parameters: An observational study.
AB  - Leukocyte cell-derived chemotaxin 2 (LECT2) is a hepatokine expressed in
      hepatocytes and appears to be involved in energy metabolism. The aim of this
      study was to determine plasma LECT2 levels in newly diagnosed type 2 diabetic
      patients and to correlate the results with various metabolic parameters.A total
      of 93 newly diagnosed type 2 diabetic patients and 80 age- and sex-matched
      nondiabetes mellitus ones were enrolled in the study. Plasma LECT2 levels were
      measured by enzyme-linked immunosorbent assay.Circulating LECT2 levels were
      approximately 1.3 times higher in newly diagnosed type 2 diabetic patients than
      in controls (mean 30.30 vs 23.23 ng/mL, P < .001). Correlation analysis showed
      that LECT2 was negatively associated with high-density lipoprotein-cholesterol
      (HDL-C) levels in type 2 diabetic patients and obese subjects (P < .05). In
      multiple stepwise regression analysis, HDL-C, HOMA-IR, BMI, FINS, and TG were
      significantly independent determinants for LECT2 (P < .05).Our study showed that
      circulating LECT2 concentrations are significantly higher in newly diagnosed type
      2 diabetic patients and further elevated in obese type 2 diabetic patients. LECT2
      concentrations are significantly negatively associated with HDL-cholesterol
      levels in newly diagnosed type 2 diabetic patients and obese subjects.

PMID- 29642179
TI  - New observation of microcystic macular edema as a mild form of cystoid macular
      lesions after standard phacoemulsification: Prevalence and risk factors.
AB  - We present the new observations of postoperative microcystic macular edema (MME)
      as a mild form of cystoid macular lesions (CMLs) after standard
      phacoemulsification.To report the incidence, risk factors, and pathophysiology of
      MME compared to conventional concept of pseudophakic cystoid macular edema (CME),
      we retrospectively reviewed patients' records. Pseudophakic CMLs were defined as
      any cystic fluid collections that were newly formed after cataract surgery,
      confirmed by preoperative and postoperative optical coherence tomography (OCT)
      examinations. CMLs were classified into 2 groups, which are CME and MME,
      according to the change the central retinal thickness. The dataset consisted of
      316 patients (mean age, 67.52 +/- 12.95 years; range, 42-87 years). Topical
      nonsteroidal anti-inflammatory drug (NSAID) were administered in 197 eyes during
      the perioperative period; 147 eyes were not treated. CMLs were present in 22 out
      of 344 (6.39%) eyes. Six of 344 eyes (1.74%) had CME and 16 of 344 eyes (4.65%)
      had MME. The incidence of MME significantly decreased in the group of patients
      treated with topical NSAIDs (P = .039), while the incidence of CME was not
      different in both groups (P = .408). All of the patients with MME were
      experienced improvement with only topical NSAIDs. However, 67% (4/6) of patients
      with CME did not improve with topical NSAIDs alone and needed additional
      treatments. Pseudophakic MMEs were more likely to have a history of diabetic
      retinopathy, epiretinal membrane, and eyes were not treated with topical
      NSAID.This study showed a wide clinical spectrum of CMLs. MME has not been
      included in the conventional definition of pseudophakic CME. Topical NSAIDs could
      decrease the CML incidence. People with risk factors for CML should use topical
      NSAIDs and undergo regular follow-up OCT examinations.

PMID- 29642180
TI  - Clinicopathological significance of cystatin A expression in progression of
      esophageal squamous cell carcinoma.
AB  - We previously conducted transcriptome analysis of a paired specimen of normal and
      esophageal squamous cell carcinoma (ESCC) tissues and found that mRNA expression
      of cystatin A (CSTA), a member of the cystatin superfamily, was perturbed in
      tumors compared with that in the background mucosa. However, little is known
      about the significance of CSTA expression in ESCC.The mRNA expression of CSTA was
      evaluated by qRT-PCR using 28 paired frozen samples of tumor and nontumor
      mucosae. The protein expression of CSTA was evaluated by the immunostaining of
      formalin-fixed, paraffin-embedded sections of ESCC samples from 59 patients who
      underwent surgery, and its relationship with clinical features was analyzed.The
      mRNA expression of CSTA was significantly decreased in ESCC compared with that in
      matched normal mucosa (P < .0001). The protein expression of CSTA was limited in
      stratum granulosum and stratum spinosum but not in stratum basal in normal
      esophageal mucosa. It was reduced in all ESCC tissue samples compared with normal
      tissues; however, CSTA expression levels in tumors showed considerable variation.
      Of the 59 samples, 20 did not express CSTA, whereas 39 clearly expressed it. The
      expression of CSTA in tumors was significantly associated with pT classification
      (deeper tumor invasions) (P = .0118) and advanced TNM stages (P = .0497). In CSTA
      positive tumor samples, CSTA-expressing cancer cells often expressed Ki67, a
      proliferation marker, which was in sharp contrast to normal mucosa, where Ki67
      expressing cells were limited to the basal layer and did not express CSTA.
      Furthermore, CSTA expression was observed in all 22 lymph node metastases
      analyzed.Relatively high levels of CSTA expression in tumors were correlated with
      tumor progression and advanced cancer stage, including lymph node metastasis.

PMID- 29642181
TI  - Associations between serum vitamin D and the risk of female reproductive tumors:
      A meta-analysis with trial sequential analysis.
AB  - BACKGROUND: Female reproductive tumors are common with high morbidity and
      mortality worldwide; however, the association between gynecological tumors and
      serum vitamin D is controversial. The aim of this meta-analysis was to evaluate
      the relationship between insufficiency of serum vitamin D and the occurrence of
      benign and malignant gynecological tumors. METHODS: Studies from inception to
      June 2017 were searched in the electronic databases: National Library of Medicine
      (PubMed), Web of Science (Clerivate), and Cochrane Database of Systematic Reviews
      (Cochrane Library, CDSR) by 2 investigators independently. Odds ratios (ORs) with
      95% confidence intervals (CIs) were calculated using a random-effects model.
      STATA 12.0 Software and Trial Sequential Analysis (TSA) software were applied for
      data analyses. RESULTS: Overall, 8 studies (including 2391 patients and 5798
      patients with and without female reproductive tumors, respectively) were eligible
      for the present meta-analysis. In the subsequent meta-analysis, the occurrence of
      vitamin D deficiency in the case and control groups were 52.36% and 48.70%,
      respectively; women with female reproductive benign and malignant tumors were
      55.57% and 50.59%, respectively. Although, no conclusive association was found
      between vitamin D deficiency and female reproductive tumors (OR, 1.05; 95% CI,
      0.85-1.31); vitamin D deficiency may be a risk factor of malignant female
      reproductive neoplasm, as shown by the pooled OR (95% CI):1.17 (1.02-1.33).
      Furthermore, based on the OR values, association of vitamin D insufficiency with
      disease type, study location, number of patients, and methods for detecting CLA
      was observed. Similar results in the sensitivity analysis were observed. TSA
      showed that the cumulative Z-curve crossed the traditional boundary line, rather
      than crossing the trial sequential monitoring boundary. However, the cumulative
      information failed to reach the required information size. CONCLUSIONS:
      Currently, vitamin D deficiency appears to be a common issue in females, and
      there may be an urgent need to improve the level of vitamin D. Furthermore,
      vitamin D deficiency may be a non-negligible risk factor of malignant female
      reproductive neoplasm. Undoubtedly, more trials are required in the future
      according to TSA.

PMID- 29642182
TI  - Human immunodeficiency virus infection and mortality risk among lung cancer
      patients: A systematic review and meta-analysis.
AB  - BACKGROUND: Previous studies have suggested that patients with human
      immunodeficiency virus (HIV) infection are at higher risk of lung cancer, but the
      impact of HIV infection on the risk of mortality among lung cancer patients is
      still unclear. We conducted a systematic review and meta-analysis to clarify the
      association between HIV infection and mortality risk among lung cancer patients.
      METHODS: PubMed and Embase databases were searched to identify studies assessing
      the association between HIV infection and mortality risk among lung cancer
      patients. Only studies reporting adjusted relative risk (RR) of mortality among
      lung cancer patients with HIV infection were included. Meta-analysis of random
      effect model was utilized to calculate the pooled RR with 95% confidence interval
      (CI). RESULTS: Twelve cohort studies were finally included. Compared with lung
      cancer patients without HIV infection, the pooled RR of mortality among lung
      cancer patients with HIV infection was 1.48 (95% CI, 1.22-1.78, P < .001; I =
      88.6%). After excluding 2 studies with low quality, HIV infection was still
      significantly associated with an elevated risk of mortality among lung cancer
      patients (RR = 1.51, 95% CI, 1.25-1.82, P < .001; I = 89.8%). Sensitivity
      analysis showed that the statistical significance of the pooled RR was not
      changed by excluding any one study. CONCLUSION: The outcomes from the meta
      analysis provide strong evidence for the elevated risk of mortality among lung
      cancer patients with HIV infection, and HIV infection is an important prognostic
      factor in lung cancer patients.

PMID- 29642183
TI  - Identification of genes related to consecutive trauma-induced sepsis via gene
      expression profiling analysis.
AB  - We aimed to identify crucial genes relevant to the development of consecutive
      trauma-induced sepsis.A microarray dataset was used to identify genes
      differentially expressed between peripheral blood samples from consecutive
      traumatized patients complicated with sepsis and not complicated with sepsis. The
      dataset GSE12624 was obtained from Gene Expression Omnibus, containing 34
      peripheral blood samples from consecutive traumatized patients complicated by
      sepsis and 36 consecutive traumatized controls. The differentially expressed
      genes (DEGs) were identified using Linear Models for Microarray Data package.
      Then, gene ontology (GO) enrichment analysis for DEGs was performed by Onto
      Express. Subsequently, the protein-protein interaction (PPI) network was
      constructed and pathway enrichment analysis was performed by Search Tool for the
      Retrieval of Interacting Genes (STRING). Furthermore, protein complexes in the
      PPI network were predicted by ClusterONE and validated through GO and Kyoto
      Encyclopedia of Genes and Genomes pathway enrichment analyses, and protein domain
      analysis.Totally, 446 upregulated and 447 downregulated DEGs were identified.
      Some DEGs were related to acyl-CoA binding (eg, ACBD6), chromosome, and
      centromeric region (eg, CENPN). In the PPI network, some DEGs were enriched in
      renin-angiotensin system (RAS, eg, AGTR1 and AGTR2). Three predicted protein
      complexes were validated in the PPI network. Some genes composing protein complex
      A were associated with cell proliferation (eg, CDC20, CCNB1, MCM4, RPA2, and
      PRIM2), and several genes composing protein complex F were implicated in
      regulation of actin cytoskeleton (eg, PFN2, ARPC2, and WASL).The results suggest
      that those DEGs may be crucial in the etiology of consecutive trauma-induced
      sepsis, and they are expected to be therapeutic targets.

PMID- 29642184
TI  - Metaplastic breast carcinoma composed of epithelial-myoepithelial carcinoma and
      squamous cell carcinoma: A case report.
AB  - RATIONALE: Metaplastic breast carcinomas are a group of breast malignancies with
      varying histomorphological characteristics and prognoses. The tumor composed of
      epithelial -myoepithelial carcinoma and squamous cell carcinoma was not reported
      previously. PATIENT CONCERNS: An 81-year-old woman presented with a palpable
      nodule in the left breast for 4 days. The ultrasonography showed multinodular
      growth and focally indistinct borders. Owing to her advanced age and possible
      early clinical staging, primary tumor resection was performed. One year later, a
      small and slow growing subcutaneous nodule was found under the incision of the
      left breast. Ultrasonography revealed an irregular, cystic and solid, hypoechoic
      mass with circumscribed borders. DIAGNOSES: Microscopic examination of the
      primary tumor revealed epithelial -myoepithelial carcinoma and squamous cell
      carcinoma. The former had a variety of architecture patterns, including nests,
      lobulations, papillary and tubular structures, and the latter showed varying
      morphological features, from squamous pearls to spindle cells. The recurrent
      tumor showed only epithelial -myoepithelial carcinoma with more aggressively
      malignant features than those seen in the primary tumor. INTERVENTIONS: An
      extensive resection of the left breast mass was performed for the recurrent
      tumor. The patient did not receive any adjuvant chemotherapy or radiation therapy
      because of the patient's advanced age. OUTCOMES: The patient has been followed up
      for 1.5 years after second surgery without evidence of tumor recurrence and
      metastasis. LESSONS: Wide local excision with adequate margins is recommended for
      elderly patients with metaplastic breast carcinoma composed of epithelial 
      myoepithelial carcinoma and squamous cell carcinoma.

PMID- 29642185
TI  - Development of massive pulmonary embolism during echocardiographic imaging: A
      case report.
AB  - RATIONALE: Pulmonary embolism (PE) is a common diagnostic consideration for
      patients who present to the emergency department (ED) with chest pain, dyspnea,
      or both. In addition, PE has a very high mortality in patients who are
      hemodynamically unstable. An electrocardiography, bedside transthoracic
      echocardiogram, and computed tomography pulmonary angiogram are usually performed
      to confirm the diagnosis. PATIENT CONCERNS: A 53-year-old man was admitted to the
      cardiology clinic with complaints of dyspnea, chest pain, and general weakness
      after walking. He had a history of hypertension and smoking. DIAGNOSIS: During
      synchronous recording of echocardiographic images, a large mobile thrombus
      detached from the right atrium, and first embolized to the right ventricle and
      then to the main pulmonary artery from the right heart chambers. Soon after,
      shortness of breath developed which clinically worsened the patient.
      Transthoracic echocardiogram which demonstrated the thrombus in the pulmonary
      artery or right heart chambers was suspected of causing acute massive PE.
      INTERVENTIONS: The patient was transferred to Critical Care Unit for monitoring;
      100 mg of alteplase was initiated immediately and alleviated the hemodynamic
      instability within 2 hours of intravenous administration. OUTCOMES: To the best
      of our knowledge, this is the first synchronous echocardiographic recording
      showing the embolization of a thrombus from the right atrium, first to the right
      ventricle and then to the main pulmonary artery. LESSONS: Transthoracic
      echocardiography provides a safe, rapid, and noninvasive diagnostic tool for
      evaluation of suspected massive PE. Thrombolytic therapy is useful for treating
      acute massive PE that leads to hemodynamic instability.

PMID- 29642186
TI  - Rebound thymic hyperplasia after adrenalectomy in a patient with Cushing syndrome
      caused by adrenocortical adenoma: A case report.
AB  - RATIONALE: The development of rebound thymic hyperplasia (RTH) has been reported
      in patients who have recovered from stressful conditions such as surgery and
      steroid therapy. We report a case of RTH following the resolution of
      hypercortisolism after adrenalectomy for the treatment of adrenocortical adenoma
      in a patient with Cushing syndrome. PATIENT CONCERNS: A 5-month-old female infant
      with a history of overeating, hirsutism, and excessive weight gain for the
      previous 2 months was referred to the hospital. The laboratory results revealed
      elevated 24-hour urinary free cortisol levels. An overnight dexamethasone
      suppression test showed no response. Abdominal imaging revealed a right-sided
      suprarenal mass measuring 4_3cm. Histology showed an adrenocortical adenoma.
      Thus, she underwent a right adrenalectomy. DIAGNOSES: The patient showed clinical
      improvement with weight loss and normal cortisol levels over the next 4 months.
      Six months after the operation, a chest computed tomography showed enlargement of
      the left thymic lobe, which was previously nonexistent. INTERVENTIONS: A fine
      needle aspiration biopsy was performed, and histological examination revealed
      diffuse thymic hyperplasia. OUTCOMES: At the 1-year follow-up, the chest imaging
      studies showed resolution of the RTH. LESSIONS: An understanding of RTH after
      adrenalectomy as a treatment for cortisol-producing adrenocortical tumors is
      important for the prevention of unnecessary surgical intervention and therapy.

PMID- 29642187
TI  - The incidence of cardiovascular events in Italian patients with systemic lupus
      erythematosus is lower than in North European and American cohorts: implication
      of disease-associated and traditional risk factors as emerged by a 16-year
      retrospective GIRRCS study: GIRRCS=Gruppo Italiano di Ricerca in Reumatologia
      Clinica e Sperimentale.
AB  - Previous study from our group has pointed out a lower number of cardiovascular
      (CV) events in Italian patients with systemic lupus erythematosus (SLE) than in
      North European and American ones. This study aims to assess the incidence of the
      first CV event in a large, multicenter, Italian cohort of patients with SLE and
      search for differences in disease and traditional risk factors among distinct
      cohorts.Clinical charts of SLE patients consecutively admitted to 5 Italian
      rheumatologic centers from November 1st 2000 to December 31st 2015 and free of CV
      events at baseline were retrospectively studied. CV cumulative incidence (ie, the
      proportion of patients who experienced a new CV event over the follow-up period)
      and CV incidence rate (ie, the number of events in the cohort divided by the
      total number of years at risk) were evaluated. The detected incidences were
      compared with those reported in SLE cohorts from other countries.The median
      duration of follow-up was 6 years (IQR = 3-11). During the observational period,
      37 (cumulative incidence = 7.2%) patients had a first episode of CV event with an
      incidence rate of 10.1/1000 person-years. The CV cumulative incidence and
      incidence rate detected in our Italian cohort were lower than those from most
      North European and American cohorts, characterized by a high impact of
      traditional risk factors. Nevertheless, the cumulative incidence was similar to
      that reported in a Spanish cohort with a high frequency of traditional risk
      factors (geographic impact), while the incidence rate was only slightly higher
      than that in the Baltimore cohort, which is characterized by a strict follow-up
      of patients (medical impact).Our results confirmed that Italian lupus patients
      have a low incidence of CV events. Moreover, the geographic origin, traditional
      risk factors, and medical approach appear to have an impact on CV disease in SLE.

PMID- 29642188
TI  - Association between blood cholesterol and sodium intake in hypertensive women
      with excess weight.
AB  - Restricted sodium intake has been recommended for more than 1 century for the
      treatment of hypertension. However, restriction seems to increase blood
      cholesterol. In women with excess weight, blood cholesterol may increase even
      more because of insulin resistance and the high lipolytic activity of adipose
      tissue.The aim of this study was to assess the association between blood
      cholesterol and sodium intake in hypertensive women with and without excess
      weight.This was a cross-sectional study with hypertensive and nondiabetic women
      aged 20 to 59 years, recruited at the primary healthcare units of Maceio,
      Alagoas, Brazilian Northeast. Excess weight was defined as body mass index (BMI)
      >=25.0 kg/m. Sodium intake was estimated by the 24-hour urinary excretion of
      sodium. Blood cholesterol was the primary outcome investigated by this study, and
      its relationship with sodium intake and other variables was assessed by Pearson
      correlation and multivariate linear regression using a significance level of
      5%.This study included 165 hypertensive women. Of these, 135 (81.8%) were with
      excess weight. The mean sodium intake was 3.7 g (+/-1.9) and 3.4 g (+/-2.4) in
      hypertensive women with and without excess weight, respectively. The multiple
      normal linear regression models fitted to the "blood cholesterol" in the 2 groups
      reveal that for the group of hypertensive women without excess weight only 1
      independent variable "age" is statistically significant to explain the
      variability of the blood cholesterol levels. However, for the group of
      hypertensive women with excess weight, 2 independent variables, age and sodium
      intake, can statistically explain variations of the blood cholesterol
      levels.Blood cholesterol is statistically inversely related to sodium intake for
      hypertensive women with excess weight, but it is not statistically related to
      sodium intake for hypertensive women without excess weight.

PMID- 29642189
TI  - Nonleukemic granulocytic sarcoma of orbit after blunt trauma: A case report and
      review of literature.
AB  - RATIONALE: Granulocytic sarcoma without invasion of bone marrow or blood is very
      rare. The diagnosis of it is usually overlooked and the treatment has not reached
      a consensus. Meanwhile, the onset of this kind of disease is not clear. PATIENT
      CONCERNS: Diagnose patients in early stage and help choose the right treatment
      strategies. DIAGNOSES: The ultimate diagnosis was nonleukemic granulocytic
      sarcoma after blunt trauma. INTERVENTIONS: Surgery was the initial treatment
      option. Chemotherapy including idarubicin (70 mg, D1-D3) and cytosine arabinoside
      (100 mg, D1-D7) and radiotherapy of total 3,060 cGy were then administered but
      failed to control the disease. Hematopoietic stem cell transplantation was
      finally administered. OUTCOMES: No evidence of disease progression or spread
      according to the latest follow-up. LESSONS: The etiology of nonleukemic
      granulocytic still remains unclear, though trauma seems to be a potential
      predisposing factor and deserves more attention for early diagnosis and timely
      and proper treatment. Systemic chemotherapy is more effective than radiotherapy
      or surgery. Hematopoietic stem cell transplantation is an alternative choice
      after the failure of chemotherapy.

PMID- 29642190
TI  - Treatment of primary tracheal glomus tumors: Two case reports and a literature
      review.
AB  - RATIONALE: Glomus tumors (GTs) are rare soft tissue neoplasms. Several treatment
      options have been reported for tracheal GTs including thoracotomy, bronchoscopic
      electrocautery, Nd: YAG laser, and cryotherapy. However, few studies have
      evaluated the ideal treatment for tracheal GTs. PATIENT CONCERNS: A 30-year old
      man who presented with cough, and expectoration for 1 month, and who had been
      diagnosed as having a tracheal neoplasm by cervical, and thoracic computed
      tomography (CT). The patient was a47 years old man. He was admitted to our
      hospital presenting with intermittent hemoptysis for 3 years. Thoracic CT
      revealed a round tumor on the right posterior tracheal wall. DIAGNOSES: Both of
      them were diagnosed as benign GTs. Histopathology of the tumor showed clusters of
      round epithelioid cells with eosinophilic cytoplasm, and uniform round to ovoid
      nuclei surrounding dilated capillaries. Immunohistochemical staining was positive
      for smooth muscle actin (SMA). INTERVENTIONS: The tracheal tumor of first patient
      was located at the level of C7-T1. Tumor resection was performed under fiberoptic
      bronchoscopy. The tracheal tumor in second patient was located in the lower
      trachea. Surgical tracheal resection and anastomosis were performed. OUTCOMES:
      Both of them achieved good results and no recurrence was seen at the final follow
      up LESSONS:: We recommend choosing the most appropriate approach to manage
      tracheal GTs based on patients' general condition, and tumor characteristics to
      obtain an excellent prognosis. Our 2 cases of tracheal GT were managed by
      different approaches, and both achieved good results.

PMID- 29642191
TI  - Intrauterine endometrial cyst after low uterine incision: A case report with
      literature review.
AB  - RATIONALE: During the surgical procedure, endometrial cells can be seeded into
      the wound edge of the uterine wall, developing into scar endometriosis. Due to
      the extremely low incidence, estimation of its prevalence is still unavailable.
      Even rarer might be the scar endometriosis in uterine cavity, to our best
      knowledge, a situation has not been reported yet. PATIENT CONCERNS: A 37-year-old
      woman complained of heavier and prolonged menstruation as well as pelvic pain
      during menses for more than 4 months. An endometrial cyst in diameter of 6 cm in
      uterine cavity was revealed by transvaginal ultrasound. Her surgical history was
      significant for 1 caesarean section and 1 abdominal myomectomy through transverse
      incision of lower uterine segment. DIAGNOSES: Space-occupying lesions in uterine
      cavity, moderate anemia and scar uterus. INTERVENTIONS: The hysteroscopy was
      performed and a multilocular cyst full of chocolate-like fluid was removed.
      Pathological examination confirmed endometrial glands in the removed cyst tissue.
      OUTCOMES: During the follow-up visits at 1 and 6 months after surgery, the
      patient denied any special discomfort. Her postoperative transvaginal ultrasound
      showed an enlarged uterus with no lesion in uterine cavity. To achieve a better
      surveillance, a 3-year period of follow-up after surgery at a 6-month interval
      was suggested. LESSONS: Intrauterine endometriosis should be considered in
      patients of pelvic surgery history with pelvic pain, menstrual disorder, and
      intrauterine cystic mass.

PMID- 29642192
TI  - Bullous pemphigoid associated with chronic hepatitis C virus infection in a
      hepatitis B virus endemic area: A case report.
AB  - INTRODUCTION: Bullous pemphigoid is a type of acute or chronic autoimmune disease
      that involves subepidermal skin lesions with bulla formation. Although viral
      infections, such as, human herpes virus (HHV), human immunodeficiency virus,
      cytomegalovirus, Epstein-Barr virus, HHV-6, hepatitis B virus (HBV), and
      hepatitis C virus (HCV), are known factors of bullous pemphigoid, HCV infection
      has only been rarely associated factor, especially in HBV endemic area. A 78-year
      old man was admitted to our hospital due to erythematous bulla of onset 3 months
      before presentation affecting his entire body. Pathologic findings, that is,
      subepidermal bullae containing eosinophils and neutrophils with superficial
      perivascular lymphocytic and eosinophilic infiltration, were consistent with
      bullous pemphigoid. Anti-HCV was positive and HCV quantitative real-time
      polymerase chain reaction (PCR) was 1.25 x 10 IU/mL. HCV genotype was 2a. After a
      diagnosis of bullous pemphigoid associated with chronic HCV infection was
      reached, he was treated with oral methylprednisolone for bullous pemphigoid, and
      his skin lesions improved. Oral direct-acting antiviral agents (sofosbuvir plus
      ribavirin) were prescribed for chronic hepatitis C, and sustained viral response
      was achieved. CONCLUSION: The authors report a rare case of bullous pemphigoid
      associated with chronic HCV infection in a HBV endemic area and advise that HCV
      should be considered in the differential diagnosis of factors precipitating
      bullous pemphigoid, even in HBV endemic areas.

PMID- 29642193
TI  - Successful chemotherapeutic treatment for metastatic littoral cell angioma: A
      case report.
AB  - RATIONALE: Metastatic littoral cell angioma (LCA) is extremely rare. No standard
      therapeutic strategy has been established, and the impact of chemotherapy has not
      yet been evaluated. PATIENT CONCERNS: A 61-year-old woman was admitted because of
      bicytopenia. She had a splenectomy for LCA of the spleen 10 years earlier. Bone
      marrow aspiration was normal, and a computed tomography (CT) scan showed
      hepatomegaly with multiple liver tumors. DIAGNOSES: Liver biopsy samples showed
      macrophage-like cell infiltration in the hepatic sinusoids. Metastatic LCA was
      diagnosed based on immunohistochemistry, imaging tests, and the clinical course.
      INTERVENTIONS: Immunosuppressive agents, such as prednisolone and cyclosporine,
      were ineffective. Next, cytotoxic agents, such as etoposide, paclitaxel, and
      vincristine, were administered. OUTCOMES: Cytotoxic agents showed a prominent
      effect against LCA. CT showed improvement of the hepatomegaly, and fluoro
      deoxyglucose (FDG) uptake decreased markedly at a follow-up FDG- positron
      emission tomography (PET) scan. LESSONS: Chemotherapeutic treatment based on
      hemophagocytic syndrome or angiosarcoma might have anti-tumor activity against
      metastatic LCA. Analysis of the molecular characteristics of this tumor is needed
      to develop better treatment options.

PMID- 29642194
TI  - Poor pathogenetic role of luminal obstruction in the development of appendicitis:
      A case report.
AB  - RATIONALE: In developed countries, the incidence of acute appendicitis is about
      95 cases out of 100,000 per year, being one of the most common urgencies in
      general surgery worldwide. However, its pathogenesis is still poorly understood.
      Direct luminal obstruction (by a fecalith, lymphoid hyperplasia, or impacted
      stool) is reported to be the primary and principal cause of acute appendicitis.
      PATIENT CONCERNS: During October 2016 a 58-year-old woman was operated because of
      a clinical recurrence of Crohn's disease. At surgery, performed through single
      incision laparoscopy, we observed an exceptional finding. DIAGNOSES: Despite a
      previous ileo-cecal resection, the appendix was still present and vascularized by
      small vessels within the mesoappendix connected to the neo-terminal ileum
      mesentery; it was about 5 cm long and macroscopically not inflamed even if its
      base was clearly no longer connected with the cecum. OUTCOMES: The patient
      underwent ileo-colic resection with en-bloc removal of the appendix. With a
      narrow metallic stylet probe we carefully tried to enter the appendix lumen
      through the opposite side from its fundus but we were not able to enter it before
      cutting the wall with scissors. Pathological examination confirmed the Crohn's
      disease recurrence affecting the small bowel and the appendix lumen obstructed in
      the presence of a fecalith but without any sign of inflammation. LESSONS: This
      finding seems to highlight the poor pathogenetic role of luminal obstruction in
      the development of acute appendicitis.

PMID- 29642195
TI  - Treatment of tuberculous aortic pseudoaneurysm associated with vertebral
      tuberculosis: A case series and a literature review.
AB  - RATIONALE: Tuberculous aortic pseudoaneurysm associated with vertebral
      tuberculosis is a rare disease but with very high mortality. We review the
      literature and find 19 reports with 22 patients. Here we report three cases with
      vertebral tuberculosis, who also have tuberculous pseudoaneurysm of the aorta.
      These patients were treated by different methods. We try to analyze the
      epidemiology, pathogenesis, presentation, and management of this disease to find
      the best treatment. PATIENT CONCERNS: The patients presented with different
      symptoms such as pain (chest, abdominal or back), fever, blood volume reduction
      or hemorrhagic shock symptoms. Large mass also could be observed by imaging. In
      addition to clinical manifestations, enhanced computed tomography or magnetic
      resonance imaging could also help the diagnosis of this disease. DIAGNOSES:
      Tuberculous aortic pseudoaneurysm associated with vertebral tuberculosis.
      INTERVENTIONS: Three patients were treated with anti-tuberculosis(TB) drugs or
      combined with different sequences surgical treatment: Case 1 refused to receive
      pseudoaneurysm surgery and only had anti-TB drug treatment; Case 2 received
      thoracic spinal surgery first; Case 3 received endovascular stent grafting.
      OUTCOMES: Two patients (case 1 and case 2) who refused to undergo aneurysm
      surgery died. The last patient (case 3) underwent endovascular repair and
      antibiotic therapy for tuberculosis, and the postoperative course was uneventful;
      the patient recovered and survived. LESSONS: Once the diagnosis of tuberculous
      pseudoaneurysm is confirmed, surgical treatment should be provided immediately
      combined with anti-tuberculosis drugs. The aim of the treatment is to save lives,
      prevent relapse, and facilitate the return to normal life, regardless of the size
      of the pseudoaneurysm. The pseudoaneurysm should be treated first to prevent
      aneurysm rupture before the vertebral tuberculosis surgery.

PMID- 29642196
TI  - Ascending aortic dilation in adult patients with congenital ventricular septal
      defect: An observational study.
AB  - Many adult patients with congenital ventricular septal defect (VSD) also
      developed ascending aortic dilation, but few report the clinical features and
      surgical management of these patients. This study was designed to study ascending
      aortic dilation in adult patients with congenital VSD, and summarized the
      treatment experience and prognosis.To assess the clinical features and surgical
      management, we performed a retrospective analysis on preoperative data,
      intraoperative data, and postoperative data from the adult patients with
      congenital VSD who developed ascending aortic dilation in our institution from
      February 2010 to December 2016.From February 2010 to December 2016, we operated
      on 13 adult patients (12 males, 92.31%) with VSD who developed ascending aortic
      dilation. Median age was 37 (interquartile range 14) years. All patients suffered
      from perimembranous VSD and received surgical treatment. Their symptoms were all
      improved after surgery, no deaths occurred.Surgery is feasible for the ascending
      aortic dilation in adult patients with congenital VSD. Both proper perioperative
      treatment and close monitoring are required for the successful surgery.

PMID- 29642197
TI  - Lower limb immobilization device induced small setup errors in the radiotherapy.
AB  - The aim of this study was to design a lower limb immobilization device and
      investigate its clinical application in the radiotherapy of the lower
      limbs.Around 38 patients who underwent lower limb radiotherapy using the designed
      immobilization device were included in this study. The setup errors were
      calculated by comparison of the portal images and the simulator films or digital
      reconstructed radiographs (DRRs).From all 38 patients accomplished the
      radiotherapy using this device, 178 anteroposterior portal images and 178 lateral
      portal images were used for the analysis of the positional accuracy. Significant
      differences were observed in the setup error of the head-foot direction compared
      with the left-right direction (t = 3.404, P = .002) and the anterior-posterior
      directions (t = 3.188, P = .003). No statistical differences were identified in
      the setup error in the left-right direction and anterior-posterior direction (t =
      0.497, P = .622).The use of the in-house designed lower limb immobilization
      device allowed for relatively small setup errors. Furthermore, it showed
      satisfactory accuracy and repeatability.

PMID- 29642198
TI  - Association between interleukin 37 (rs3811047) polymorphism and multiple
      autoimmune diseases in a Chinese population: A PRISMA-compliant meta-analysis.
AB  - OBJECTIVE: Emerging evidence suggests that interleukin 37 (IL-37) plays an
      important role in the pathogenesis of several autoimmune diseases (ADs), but the
      correlations are still unclear. We conducted a meta-analysis to explore whether
      IL-37 gene (rs3811047) polymorphism was associated with susceptibility to
      multiple ADs in a Chinese population. METHODS: Relevant studies were searched in
      the PubMed, Embase, Chinese National Knowledge Infrastructure, and Chinese
      Wangfang databases up to August 31, 2017. Odds ratio (OR) and its 95% confidence
      interval (95% CI) was used to estimate the strength of the association in
      different genetic models. The results of fixed or random models were adopted
      according to the heterogeneity. Publication bias and sensitive analysis were also
      performed to evaluate the reliability of results. RESULTS: A total of 3161
      patients and 4078 controls from 6 studies were included in this meta-analysis.
      Pooling all data together, a significant association between IL-37 gene
      (rs3811047 A/G) polymorphism and susceptibility to ADs in the Chinese population
      was found in all 4 genetic models (allelic model A vs G: OR = 0.73 95% CI =
      0.67~0.79; recessive model AA + AG vs GG: OR = 0.72, 95% CI = 0.65~0.79; dominant
      model AA vs AG + GG: OR = 0.59, 95% CI = 0.45~0.77; homozygous model AA vs GG: OR
      = 0.55, 95% CI = 0.42~0.72). No heterogeneity and publication bias was detected
      in all models. Sensitive analysis indicated that all of the positive results are
      reliable. CONCLUSION: The IL- 37 (rs3811047) polymorphism contributes to the
      development of ADs in a Chinese population.

PMID- 29642199
TI  - Extent of simultaneous radiation dose and iodine reduction at stable image
      quality in computed tomography of the chest: A systematic approach using
      automated tube voltage adaption and iterative reconstructions.
AB  - BACKGROUND: Aim of this study was to systematically combine tube voltage
      adaptation and iterative reconstructions for reduction of iodine and radiation
      dose. METHODS: Settings for the study protocol were evaluated in ex-ante trials
      to provide image quality that is comparable to a reference protocol at 120 kV
      with tube current modulation. Consecutive patients were randomized to undergo
      computed tomography (CT) of the chest using the study protocol (n = 62) or
      reference protocol (n = 50). Objective and subjective image quality was assessed
      and compared. RESULTS: Tube voltage was decreased to 100 kV in 47 patients and to
      80 kV in 15 patients in the study group. The iodine dosage (16.1 vs 10.5 g) and
      the effective radiation dose (3.6 vs 2.5 mSv) were significantly decreased in the
      study group (both P < .001). Contrast-to-noise ratio was comparable in the
      pulmonary trunk and increased in the aorta (P < .01). Subjective image quality
      was comparable without statistically significance. CONCLUSIONS: Simultaneous
      reductions in iodine dosage and radiation dose by one-third are feasible for CT
      of the chest.

PMID- 29642200
TI  - A systematic review and network meta-analysis protocol of neoadjuvant treatments
      for patients with gastric cancer.
AB  - BACKGROUND: National Comprehensive Cancer Network (NCCN) guidelines recommend
      surgery, chemotherapy, and radiation therapy for gastric cancer patients.
      Neoadjuvant treatments as the administration of therapeutic agents before a main
      treatment gained in more and more attention. However, the role of neoadjuvant
      treatments is still controversial. The main aim of this systematic review and
      network meta-analysis is to assess the relative efficacy of different neoadjuvant
      treatment regimens for gastric cancer using network meta-analysis method.
      METHODS: We will search 5 electronic databases to identify randomized controlled
      trials (RCTs) and non-RCTs compared the efficacy differences of surgery alone
      (S), preoperative chemotherapy follow by surgery (CTS), preoperative radiotherapy
      follow by surgery (RTS), and preoperative chemoradiotherapy follow by surgery
      (CRTS) for patients with gastric cancer. The risk of bias tool from the Cochrane
      Handbook version 5.1.0 will be used to assess the risk of bias of RCTs, and the
      risk of bias in nonrandomized studies of interventions (ROBINS-I) for non-RCTs.
      Data will be analyzed using R-3.4.1 software. RESULTS AND CONCLUSION: The results
      of present network meta-analysis will estimate the relative efficacy among all
      interventions and rank the interventions even if head-to-head comparisons are
      lacking and will provide more evidence for clinicians, researchers, and patients
      in the management of gastric cancer.Protocol registration number: CRD42017074956.

PMID- 29642201
TI  - Robotic surgeries for patients with colorectal cancer who have undergone
      abdominal procedures: Protocol for meta-analysis.
AB  - BACKGROUND: Although the safety and the advantages of laparoscopic and robotic
      colorectal surgeries have been confirmed, the use of both modalities in patients
      with previous abdominal surgeries (PAS) history remains uncertain. Herein, we
      perform a meta-analysis to investigate the impact of PAS on perioperative
      recovery outcomes from laparoscopic and robotic colorectal surgeries. METHODS: We
      will search PUBMED, the Cochrane Library, the Chinese Biomedical database (CBM),
      WanFang data, China National Knowledge Infrastructure (CNKI) up to January 2018.
      Studies will be screened by title, abstract, and full text independently and in
      duplicate. Studies that report the impact of PAS on perioperative recovery
      outcomes from laparoscopic and robotic colorectal surgeries will be eligible for
      inclusion. Outcome variables will be assessed included combined resection,
      conversion, operation time, blood loss, number of retrieved lymph nodes, days to
      soft diet intake, length of hospital stay, and postoperative complications.
      Assessment of risk of bias and data synthesis will be performed using STATA SE
      12.0. Heterogeneity among studies will be assessed using the I statistic.
      RESULTS: Randomized controlled trials, prospective cohort studies, and propensity
      matched comparative studies will be used for the quantitative synthesis of the
      meta-analysis to evaluate the impact of PAS on perioperative recovery outcomes
      from laparoscopic and robotic colorectal surgeries. CONCLUSIONS: We aim to draw
      an objective conclusion of the comparisons in aspects of perioperative outcomes
      and provide physicians level I evidences for clinical decision makings.

PMID- 29642202
TI  - S-1-based concurrent chemoradiotherapy in the treatment of locally advanced non
      small cell lung cancer: A systematic review and meta-analysis protocol.
AB  - BACKGROUND: Lung cancer is the leading cause of cancer-related deaths in the
      world, and non-small cell lung cancer accounts for > 75% of all lung cancer
      cases. Cisplatin-based concurrent chemoradiotherapy has become the standard
      treatment for locally advanced non-small cell lung cancer (NSCLC). Third
      generation chemotherapy agents plus cisplatin have been most commonly used in
      concurrent chemoradiotherapy, which is also associated with more adverse effects
      and acute toxicities. S-1 as an oral chemotherapeutic agent exhibits higher
      antitumor activity, less adverse effects, and better biological availability.
      Recently, studies illustrated S-1-based concurrent chemoradiotherapy also had
      excellent effects in the treatment of locally advanced NSCLC. METHODS: A
      systematic literature search will be performed through February 2018 using
      MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and Google
      Scholar for relevant articles published in any language. Randomized controlled
      trials and prospective comparative studies will be included. All meta-analyses
      will be performed using Review Manager software. The quality of the studies will
      be evaluated using the guidelines listed in the Cochrane Handbook. The Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses statements will be
      followed until the findings of the systematic review and meta-analysis are
      reported. RESULTS: The results of this systematic review and meta-analysis will
      be published in a peer-reviewed journal. CONCLUSION: Our study will draw an
      objective conclusion of the efficacy and safety of S-1-based chemoradiotherapy in
      the treatment of locally advanced unresectable NSCLC and provides level I
      evidence for clinical decision makings.

PMID- 29642203
TI  - Evaluation of effect and safety of arthroscopic surgery with three different
      operative approaches in patients with terrible triad of the elbow: A comparative
      study.
AB  - BACKGROUND: The terrible triad of the elbow (TTE) is a difficult injury, and the
      usual TTE consists of posterior dislocation of the elbow, radial head fracture,
      and coronoid fracture. The target of this retrospective study is to explore the
      effect, postoperative complications, and prognostic factors in patients with TTE
      undergoing arthroscopic surgery with three different operative approaches.
      METHODS: Patients with TTE underwent arthroscopic surgery were treated using
      lateral, anterior medial, or combined lateral and anterior medial approaches,
      respectively. In order to analyze the postoperative complications and the effect
      of arthroscopic surgery for patients with TTE, the function of elbow joint before
      and after the surgery was evaluated and the flexion-extension of elbow joint and
      rotation of elbow joint and forearm were measured. RESULTS: The evaluation
      results obtained from patients underwent 3 different operative approaches
      revealed that after surgery, patients receiving arthroscopic surgery using
      combined lateral and anterior medial approach had superior flexion-extension of
      elbow joint, rotation of elbow joint and forearm, higher Mayo Elbow Performance
      Score (MEPS) and more cases of Broberg-Morrey grade 0, and lower complication
      rate, compared with those using lateral or anterior medial approach. A key
      finding in the study demonstrated that fracture type, operative approach, and
      postoperative complications were factors related with the effect of arthroscopic
      surgery for patients with TTE. CONCLUSION: Collectively, the key findings
      obtained from the present study supported the notion that the effect of
      arthroscopic surgery in combined lateral and anterior medial approach is much
      better than in lateral approach or anterior medial approach, and is related with
      fracture type, operative approach, and postoperative complications.

PMID- 29642204
TI  - Patterns of ocular toxoplasmosis presenting at a tertiary eye care center in
      Korean patients.
AB  - The objective of this study was to describe demographic and clinical features of
      ocular toxoplasmosis (OT) in Korean patients compared to those in other
      countries.This retrospective study comprised 46 patients diagnosed with OT. All
      participants were recruited at the uveitis clinic in Seoul St. Mary's
      Hospital.The mean age of patients was 54 years. Of 46 patients, 31 (67.4%) were
      females. Of all patients, 24 (52.2%) had definite eating history of wild boar
      meat or deer blood while 5 (10.9%) had history of close contact with cats. The
      most common forms of OT were vitritis (91.3%) combined with retinochoroiditis
      (65.2%). Active retinochoroidal lesion was located at the peripheral retina in 18
      (39.1%) patients, central retina in 8 (17.4%) patients, and peripapillary retina
      in 4 (8.7%) patients. Seven (15.2%) cases were clinically diagnosed with typical
      OT without serologic evidence. Thirty-nine (84.8%) had serum IgG for
      toxoplasmosis. However, only 8 (17.4%) had serum IgM. In 65.2% of patients, there
      was no complication after treatment. The most common ocular complication was
      macular scar (8.7%).The present study provides demographic and clinical
      characteristics of OT in Korea, a low endemic area of Toxoplasma gondii. Acquired
      infection is the major cause of OT in Korea. Even though Korea is a low endemic
      area of Toxoplasma gondii, OT is a preventable and common cause of acquired
      infectious uveitis.

PMID- 29642205
TI  - Mature cystic teratoma of the pancreas with 30 years of clinical course: A case
      report.
AB  - RATIONALE: Mature cystic teratoma of the pancreas is an extremely rare condition
      that is challenging to manage due to inadequate preoperative histological
      diagnosis. PATIENT CONCERNS: A 36-year-old female was admitted to our hospital
      because of a complaint of worsening paroxysmal abdominal pain for over a year.
      She was diagnosed with pancreatic pseudocyst and underwent five surgical
      procedures (i.e., four external drainage and one internal drainage procedures) in
      the last 30 years. DIAGNOSES: Intraoperative frozen section analysis identified
      the tumor as a cystic teratoma, and pathological evaluation confirmed it to be a
      mature cystic teratoma. INTERVENTIONS: Explorative laparotomy was performed, and
      the tumor was then resected completely through with partial pancreatectomy, left
      colon resection, partial gastrectomy, duodenectomy, as well as inferior vena cava
      and renal vascular repair. OUTCOMES: The patient exhibited a generally good
      wellbeing without any recurrence during the 6 months of follow up. LESSONS: This
      case demonstrated the significant impacts of misdiagnosis and inappropriate
      treatments for benign disease on the patient's quality of life and highlighted
      the importance of early surgical resection with a definitive pathological
      diagnosis for pancreatic cystic teratoma.

PMID- 29642206
TI  - Progressive cystic lesion in a middle-aged patient with tuberous sclerosis
      complex: A case report.
AB  - RATIONALE: Tuberous sclerosis complex (TSC) is an uncommon multiple systems
      disorder. The main characteristics of the disease in the central nervous system
      include cortical or subcortical tubers, subependymal nodules, and subependymal
      giant cell astrocytoma. However, progressive cystic lesions in the cerebral
      hemispheres have rarely been reported in previous studies of TSC. PATIENT
      CONCERNS: We present the case of a 35-year-old man with TSC who was admitted to
      our hospital for a sudden attack of serious headache, vomiting, and left
      hemiplegia. Brain computerized tomography and magnetic resonance imaging (MRI)
      revealed multiple subependymal calcific nodes and multiple cystic lesions in the
      right frontal, temporal, and parietal lobes. The solid nodule in the lesion
      demonstrated contrast enhancement. DIAGNOSES: The patient was diagnosed with TSC,
      but the properties of the cystic lesion in the brain were unclear and a tumor was
      suspected. INTERVENTIONS: Emergency operation was performed immediately.
      Pathological examination of the lesion revealed a vascular malformation, but no
      tumor cells. OUTCOMES: In the fourth year after the surgery, brain MRI revealed a
      relapse of the cystic mass and surgery was suggested again. However, the patient
      refused to undergo surgery again. LESSONS: This case describes an atypical MRI
      presentation of TSC occurring in middle-age. This condition can cause a life
      threatening condition and may recur after surgery. Our finding emphasizes the
      importance of neuroimaging surveillance in patients older than 25 years old and
      after lesion resection.

PMID- 29642207
TI  - Successful management of fatal peripartum cardiomyopathy in a young pregnant
      woman: A case report.
AB  - RATIONALE: Peripartum cardiomyopathy (PPCM) is a rare and life-threatening form
      of pregnancy associated myocardial disease. PATIENT CONCERNS: In the present
      report, we describe a case of a patient with PPCM at 33 weeks of gestation with
      stillbirth and cardiorespiratory failure. DIAGNOSES: Peripartum cardiomyopathy.
      INTERVENTIONS: The patient underwent emergency cesarean section (CS) and
      comprehensive medical treatments, including bromocriptine, as well as positive
      inotropic agents and diuretics after the CS. OUTCOMES: She had an uneventful
      recovery period, and was discharged 9 days after surgery. Her heart function was
      restored within 6 months after CS, and follow-up echocardiographies indicated
      normal heart function. LESSONS: This case highlights that early diagnosis and
      timely termination of pregnancy are crucial in the management of PPCM.

PMID- 29642208
TI  - Cardioprotective effect of histamine H2 antagonists in congestive heart failure:
      A systematic review and meta-analysis.
AB  - BACKGROUND: Histamine H2 antagonists (H2RAs) have long been suggested to have
      beneficial effects on congestive heart failure (CHF). However, full agreement
      about the cardioprotective effects of H2RAs is still not reached yet. Therefore,
      this study aims to clarify the effects of H2RAs on myocardial function in CHF
      patients by meta-analysis. METHODS: Electronic databases including PubMed,
      Embase, and Cochrane Library were retrieved. Randomized controlled trials
      comparing the cardiac effects of H2RAs and placebo or other medicines were
      collected. Pooled mean differences (MDs) with 95% confidence intervals (CIs) were
      calculated and meta-analysis was performed using RevMan 5.3 software. RESULTS: A
      total of 10 studies (472 participants) were included in this meta-analysis. H2RAs
      exhibited significant negative inotropic and chronotropic effects to reduce heart
      rate (MD: -3.90; 95%CI: -7.07 to -0.73, P = .02). Furthermore, although H2RAs did
      not affect the blood pressure in health volunteers, they significantly decreased
      the blood pressure of CHF patients. Additionally, H2RAs were also associated with
      significant increase in pre-ejection period and the ratio of pre-ejection period
      to left ventricular ejection time. CONCLUSION: In summary, these findings showed
      that H2RAs exerted negative inotropic and chronotropic effects to reduce heart
      rate and blood pressure, which, similar to beta-adrenergic receptor blockers,
      might decrease myocardial oxygen demand and eventually result in improvement of
      CHF symptoms. These data provided further evidence for the effect of H2RAs on
      cardiac function and novel potential strategy for treatment of CHF.

PMID- 29642209
TI  - Retrospective analysis of prognosis and risk factors of patients with stroke by
      TOAST.
AB  - To determine differences in 90-day mortality and identify risk factors among
      different etiological classifications of ischemic stroke using the Trial of ORG
      10172 in Acute Stroke Treatment (TOAST) classification.Our retrospective analysis
      included 538 ischemic stroke patients. The cause of stroke was categorized
      according to the TOAST criteria, and 90-day mortality rates were obtained through
      the patient follow-up. Age, sex, previous medical history, and clinical features
      were used in the analysis of potential risk factors.There were 38 deaths during
      the 90-day follow-up period. Patients in the undetermined cause subgroups
      experienced significantly higher mortality rate than those in subgroups with
      small artery occlusion and large artery atherosclerosis. Factors independently
      associated with 90-day mortality for patients with the large artery
      atherosclerosis stroke subtype were age (95% confidence interval [CI], 1.010
      1.192, P = .028), history of hypertension (95% CI, 3.030-99.136, P = .001), high
      blood glucose (95% CI, 1.273-2.354, P < .001), high cholesterol (95% CI, 0.017
      0.462, P = .004), high uric acid (95% CI, 2.360-64.389, P = .003), and National
      Institute of Health Stroke Scale(95% CI, 1.076-1.312, P = .001). Age (95% CI,
      1.012-1.358, P = .034) and high cholesterol (95% CI, 0.011-0.496, P = .007) were
      independently associated with 90-day mortality for patients with the small artery
      occlusion subtype of stroke.Our analysis identified that certain risk factors and
      90-day mortality differ significantly among different stroke subtypes, as
      classified by the TOAST criteria. These risk factors must be considered carefully
      to provide the best clinical management of these patients and thus reduce
      mortality.

PMID- 29642210
TI  - VEGF levels in plasma in relation to metabolic control, inflammation, and
      microvascular complications in type-2 diabetes: A cohort study.
AB  - The vascular endothelial growth factor (VEGF) level in human circulation may
      reflect the severity of endothelial dysfunction in patients with diabetes
      mellitus, which leads to diabetic microvascular complications.We determined
      plasma VEGF levels as well as metabolic control and inflammatory factors in 26
      healthy subjects and 52 type-2 diabetes mellitus (T2DM) patients with or without
      diabetic microvascular complications. Pearson correlation coefficient was used to
      evaluate the associations among those indices.The results showed that VEGF levels
      in plasma were positively correlated with fasting blood glucose level,
      glycosylated hemoglobin (HbA1c) level, type 1 helper T cell (Th1) percentage, and
      Th1/Th2 ratio, while they were negatively correlated with regulatory T cell
      percentage. Multiple linear regression analysis showed that HbA1c and Th1/Th2
      ratio were the independent predictors of VEGF levels in T2DM patients.Thus, in
      T2DM patients with poor glycemic control as well as an elevated Th1/Th2 cell
      ratio, more VEGF might be released.

PMID- 29642211
TI  - A case report of sofosbuvir and daclatasvirto treat a patient with acute
      hepatitis C virus genotype 2 monoinfection.
AB  - RATIONALE: Direct-acting antivirals (DAAs) are the first-line treatment for
      patients with chronic hepatitis C virus (HCV) infection. However, its effects on
      patients with acute HCV infection are poorly understood, and the data for
      treatment of DAAs for genotype 2 acute monoinfection patients with HCV are
      lacking. PATIENT CONCERNS: In this case report, a 26 year-old Chinese female
      acquired a tattoo and developed fatigue, nausea, and anorexia. Laboratory tests
      showed abnormal liver function. DIAGNOSES: Five months after the patient acquired
      a tattoo, laboratory tests showed anti-HCV antibody titers were 26.0 s/co, HCV
      RNA was 5.74*10 IU/mL, and HCV genotype was 2a. The patient was diagnosed with
      acute hepatitis C (AHC). INTERVENTIONS: HCV RNA did not have spontaneous
      clearance 12 weeks after the infection of the patient. The patient received
      sofosbuvir (SOF) and daclatasvir (DCV) combination treatment for 12 weeks.
      OUTCOMES: Laboratory tests showed HCV RNA was undetectable at weeks 4, and anti
      HCV antibody was in seroconversion at weeks 12 during treatment. The patient
      achieved a sustained virological response 36 weeks after the end of treatment.
      LESSONS: Patients with acute HCV genotype 2 monoinfection would benefit from
      antiviral treatment with SOF and DCV.

PMID- 29642212
TI  - Fiberoptic bronchoscopic treatment of blood aspiration and use of sugammadex in a
      patient with epistaxis: A case report.
AB  - RATIONALE: In patients with oropharyngeal and nasopharyngeal bleeding, blood
      aspiration can make airway management difficult and lead to severe pulmonary
      complications. PATIENT CONCERNS: A 44-year-old male patient with recurrent
      epistaxis underwent surgery for hemostasis. The patient aspirated blood through
      the endotracheal tube when he hiccupped during the surgery. DIAGNOSIS: The
      patient was diagnosed with blood aspiration after intraoperative fiberoptic
      bronchoscopy revealed a blood clot and viscous mucus in the airways, but no sign
      of active bleeding. INTERVENTIONS: Tracheobronchial suctioning and irrigation
      with normal saline was performed through the bronchoscope to remove the aspirated
      blood clot. Prior to emergence from anesthesia, sugammadex was administered to
      induce complete neuromuscular recovery and enable the patient to cough up any
      blood remaining in the airways. OUTCOMES: The patient was successfully extubated
      and fully recovered with no complications. LESSONS: Blood aspiration due to
      oropharyngeal or nasopharyngeal bleeding can be diagnosed and treated by
      tracheobronchial suctioning via fiberoptic bronchoscopy. In addition, sugammadex
      can enable patients to recover spontaneous breathing, facilitate extubation, and
      enable patients to cough up any blood remaining in the airways.

PMID- 29642213
TI  - Hidden blood loss and its influencing factors after percutaneous kyphoplasty
      surgery: A retrospective study.
AB  - Percutaneous kyphoplasty (PKP) surgery is generally accepted as a minimally
      invasive treatment for osteoporotic vertebral compression fractures (OVCFs).
      However, hidden blood loss (HBL) caused by this procedure is usually disregarded.
      This study aimed to investigate the amount of HBL and its influencing factors
      after PKP surgery.A total of 160 patients were retrospectively examined from
      January 2014 to January 2016, and their clinical and radiological data were
      recorded and analyzed. Preoperative and postoperative hematocrit (Hct) and
      hemoglobin (Hb) levels were also documented. HBL was calculated using Gross
      formula. Different factors, including gender, age, bone mineral density (BMD),
      number of fracture levels, hypertension, diabetes mellitus, operative time,
      percentage of vertebral height loss, percentage of vertebral height restoration,
      and cement leakage, were examined. Multivariate linear regression analysis was
      performed to elucidate the related clinical or radiological factors of HBL.A
      total of 122 patients with 169 levels were eligible for inclusion in the study.
      The mean HBL was 279 +/- 120 mL, and the postoperative Hb loss was 8.2 +/- 3.9
      g/L. Multivariate linear regression analysis revealed that HBL was positively
      associated with operative time (P = .000), percentage of vertebral height loss (P
      = .037), and percentage of vertebral height restoration (P = .000). By contrast,
      HBL was not associated with gender (P = .874), age (P = .148), BMD (P = .134),
      number of fracture levels (P = .079), hypertension (P = .259), diabetes mellitus
      (P = .495), and cement leakage (P = .975). The postoperative incidence of anemia
      significantly increased by 39.3% compared with that of the preoperative incidence
      (chi = 21.432, P = .000).For patients with OVCFs, the amount of HBL after PKP is
      much larger than that observed perioperatively. Operative time, percentage of
      vertebral height loss, and percentage of vertebral height restoration are
      influencing factors of HBL.

PMID- 29642214
TI  - Successful treatment of plasma exchange for rapidly progressive interstitial lung
      disease with anti-MDA5 antibody-positive dermatomyositis: A case report.
AB  - RATIONALE: As the initial treatment of rapidly progressive interstitial lung
      disease (RPILD) with antimelanoma differentiation-associated gene 5 antibody
      (anti-MDA5 Ab)-positive dermatomyositis (DM) patients, a combination of
      corticosteroids, cyclophosphamide, and calcineurin inhibitor is recommended.
      However, some of these patients have poor prognoses despite such intensive
      treatment. Other more effective treatments are desired. We report the case of an
      anti-MDA5 Ab-positive DM patient who had developed RPILD despite intensive
      treatments; she was treated successfully by a short-term plasma exchange (PE).
      PATIENT CONCERNS: A 71-year-old Japanese woman was admitted to the rheumatology
      department of another hospital with progressive muscle weakness of the limbs and
      erythema on both upper eyelids and the fingers of both hands. She was suspected
      of having classical DM (CDM) based on the findings of typical skin and myositis.
      Although a chest computed tomography (CT) examination showed no findings of
      interstitial pneumonia at the first visit to the department, she newly presented
      interstitial pneumonia during her admission and her anti-MDA5 Ab titer was
      elevated. DIAGNOSES: She was diagnosed with interstitial lung disease (ILD) with
      anti-MDA5 Ab-positive DM. INTERVENTIONS: She was treated with 1000 mg of methyl
      prednisolone pulse, 500 mg of intravenous cyclophosphamide therapy (IVCY)
      followed by prednisolone 40 mg/day with tapering, and oral cyclosporine 200
      mg/day. However, her interstitial pneumonia worsened with increasing breathing
      difficulty and an increasing serum ferritin level. She was transferred to our
      department, and we initiated PE as an additional treatment. OUTCOMES: After the
      PE treatment, all laboratory findings, for example, ferritin, KL-6, and the titer
      of anti-MDA5 Ab showed marked improvement, and the patient's skin symptoms and
      active interstitial pneumonia were relieved. LESSONS: Our patient's case suggests
      that PE may be effective for RPILD in anti-MDA5 Ab-positive DM patients.

PMID- 29642215
TI  - Anomalous coagulation factors in non-arteritic anterior ischemic optic neuropathy
      with central retinal vein occlusion: A case report.
AB  - RATIONALE: Non-arteritic anterior ischemic optic neuropathy (NAION) is
      characterized by sudden, painless visual loss and optic disc edema. NAION occurs
      mainly in the presence of cardiovascular disease and hypercoagulability, mainly
      in patients over 50 years of age. We experienced a case of NAION associated with
      central retinal vein occlusion (CRVO) in a young man with no underlying disease.
      PATIENT CONCERNS: A 46-year-old man was referred to our clinic following a sudden
      loss of vision in his right eye. The patient exhibited no underlying disease and
      reported no ongoing medication. Significant visual loss and visual disturbance of
      the right eye were observed. The pupil of the right eye was enlarged and an
      afferent pupillary defect was observed. On fundus examination, retinal hemorrhage
      was observed in the peripheral retina; macular edema was observed in optical
      coherence tomography analysis. However, optic disc edema was not evident. No
      abnormal findings were found in routine blood tests for hypercoagulability. After
      3 days of steroid intravenous injection, macular edema disappeared and visual
      acuity was improved, but optic disc edema began to appear. One week later, optic
      disc edema was evident and visual acuity was significantly reduced; thus, the
      patient was diagnosed with NAION. In fluorescein angiography, peripheral retinal
      ischemia was observed, suggesting that CRVO was complicated. Blood tests,
      including analysis of coagulation factors, were performed again, showing that
      coagulation factors IX and XI were increased. DIAGNOSES: Anomalous coagulation
      factors in non-arteritic anterior ischemic optic neuropathy with central retinal
      vein occlusion. INTERVENTIONS: Systemic steroids were administered. OUTCOMES: One
      month later, optic disc edema and retinal hemorrhage gradually diminished and
      eventually disappeared; however, visual acuity did not recover. CONCLUSION: In
      young patients without underlying disease, cases of NAION require careful
      screening for coagulation disorders. Even if there is no abnormality in the test
      for routine coagulation status, it may be necessary to confirm a coagulation
      defect through an additional coagulation factor assay.

PMID- 29642216
TI  - Diagnostic accuracy of cystoscopy and ultrasonography in the prenatal diagnosis
      of abnormally invasive placenta.
AB  - The aim of this study was to compare the accuracy of cystoscopy and
      ultrasonography for the prenatal diagnosis of abnormally invasive placenta (AIP),
      including its subgroups: placenta accreta (PA), placenta increta (PI), and
      placenta percreta (PP).A retrospective observational study including a total of
      85 pregnant women at high risk for AIP underwent prenatal cystoscopy and
      ultrasonography evaluations. The sensitivity (Se), specificity (Sp), positive
      predictive value, negative predictive value, and exact diagnosed were calculated
      and compared for both cystoscopy and ultrasonography. Se and Sp values of
      cystoscopy and ultrasonography were compared by means of the McNemar test.Of the
      85 patients, there were 24 (28.2%) PA, 35 (41.2%) PI, 4 (4.7%) PP, and 22 (25.9%)
      nonadherent placenta. The mean maternal age and gestational age of delivery were
      31.88 +/- 4.42 years and 36.14 +/- 1.84 weeks, respectively. No one was found to
      develop any complications with cystoscopy like urinary tract infection, or
      ureteral injury or perforations. Se in the diagnosis of AIP was 50.8% with
      ultrasonography and 61.9% for cystoscopy. Sp was 86.4% with cystoscopy and 72.7%
      for ultrasonography. In subgroups, Se with cystoscopy was 25.0%, 62.9%, and
      100.0% in PA, PI, and PP, respectively, and 37.5%, 74.3%, and 100.0%,
      respectively, for ultrasonography; Sp remained unchanged with 86.4% for
      cystoscopy and 72.7% for ultrasonography. After McNemar test, no difference was
      found in either Se or Sp between cystoscopy and ultrasonography in AIP and its
      subgroups.According to the depth of invasion, the diagnostic value of cystoscopy
      and ultrasonography is all conspicuous increased and they have similar test
      validity for prenatal diagnosis of AIP and its subgroups.

PMID- 29642217
TI  - Revision surgery after rod breakage in a patient with occipitocervical fusion: A
      case report.
AB  - RATIONALE: Rod breakage after occipitocervical fusion (OCF) has never been
      described in a patient who has undergone surgery for basilar invagination (BI)
      and atlantoaxial dislocation (AAD). Here, we present an unusual but significant
      case of revision surgery to correct this complication. PATIENT CONCERNS: A 32
      year-old female presented with neck pain, unstable leg motion in walking, and
      also BI with AAD. Her first surgery was planned to correct these conditions and
      for fusion at the occipital junction (C3-4) using a screw-rod system. At the 31
      month follow-up after her first operation, the patient complained of severe neck
      pain and limitation of motion, suggesting rod breakage. DIAGNOSES: Rod breakage
      after occipitocervical fusion for BI and AAD. INTERVENTIONS: The patient
      underwent reoperation for replacement of the broken rods, adjustment of the
      occipitocervical angle, maintenance of the bone graft bed, and fusion. OUTCOMES:
      At follow-up, the hardware was found to be in good condition, with no significant
      loss of cervical lordosis. At the 37-month follow-up after her second operation,
      the patient was doing better and continuing to recover. LESSONS: We concluded
      that nonideal choice of occipitocervical angle may play an important role in rod
      breakage; however, an inadequate bone graft and poor postoperative fusion may
      also contribute to implant failure.

PMID- 29642218
TI  - Spontaneous conversion of atrial fibrillation caused by severe hyperkalemia: A
      case report.
AB  - RATIONALE: Hyperkalemia is a life-threatening electrolyte disturbance which could
      lead to arrhythmias and potentially death. PATIENT CONCERNS: An 82-year-old male
      patient who presented typical electrocardiographic indications of hyperkalemia,
      including the absence of P waves, prolongation of QRS complex, sinoventricular
      conduction, bradyarrhythmia and tall peaked T waves. He developed a rare self
      defibrillation of atrial fibrillation to sinus rhythm due to hyperkalemia.
      Besides, he developed secondary thrombosis caused by abrupt termination of atrial
      fibrillation. DIAGNOSES: This patient was diagnosed with hyperkalemia,
      hypertension, and AF. INTERVENTIONS: He was treated with an intravenous infusion
      of calcium gluconate, insulin and dextrose, an oral kayexalate, and emergency
      hemodialysis. OUTCOMES: The patient was managed effectively and discharged with
      stable status. LESSONS: Hyperkalemia could induce malignant arrhythmia with high
      mortality. Thus we suggested more attention be paid to monitoring electrolyte
      disorders and maintaining anticoagulation treatments to avoid thromboembolism.

PMID- 29642219
TI  - Descemet's membrane detachment following uneventful phacoemulsification
      surgeries: A case report.
AB  - RATIONALE: Descemet's membrane detachment (DMD) may occur during or following
      cataract surgery, causing corneal edema and visual loss1. The incidence of DMD
      after phacoemulsification surgery is only approximately 0.5%, and mostly surgical
      related. Late onset bilateral spontaneous DMD after sequential uneventful
      cataract surgeries, is even rarer, and may result from not only surgery itself,
      but also from an underlying anatomic abnormality 2. PATIENT CONCERNS: We present
      a 80 year old female developed bilateral descemet's membrane detachment after
      sequential uncomplicated cataract surgeries. DIAGNOSIS: Bilateral Descemet's
      membrane detachment. INTERVENTIONS: One eye (left eye) was treated with
      intracameral air injection and the fellow eye (right eye) was treated with
      medical treatment only. OUTCOMES: The DMDs were reattached in both eyes after
      treatment. Surgical intervention accelerated the duration of recovery and there
      were no significant outcome differences between the right and the left eye.
      LESSONS: Even if there is a large area of DMD with visual axis involvement,
      conservative treatment with close observation might still provide a satisfactory
      result if Descemet's membrane is separated from the posterior corneal stroma by
      <=1 mm.

PMID- 29642221
TI  - Pregnancy-induced complications in IgA nephropathy: A case report.
AB  - RATIONALE: IgA nephropathy is one of the most common causes of renal
      hypertension. The clinical management of IgA renal patients during pregnancy is
      challenging, as complex pathophysiological changes may occur that affect both the
      patient's prognosis and the outcome of the pregnancy. PATIENT CONCERNS: A 36-year
      old woman with a family history of hypertension and at least one year of
      untreated mild high blood pressure was admitted to our hospital in the 28th week
      of pregnancy. She suffered from hypertensive disorder complicating pregnancy
      (HDCP) with renal insufficiency and stillbirth. Treatment with duplex
      antihypertensive drugs did not improve her blood pressure and she presented with
      abnormal renal function. DIAGNOSES: A renal biopsy led to the diagnosis of a
      grade IV IgA nephropathy (Lee's grading system) with renal hypertension.
      INTERVENTIONS: The prescribed treatment regimen consisted of low dose
      cyclophosphamide 0.2 g per day for two days, followed by daily oral
      administration of 30 mg prednisone, 30 mg Nifedipine extended-release tablets and
      80 mg Telmisartan to regulate the blood pressure. OUTCOMES: The medication with a
      combination of antihypertensive and immunosuppressive drugs led to a clinical
      improvement with a nearly normal renal function and a stable blood pressure
      during the one-year follow-up. LESSONS: This case underlines that 1) the
      pregnancy outcomes of patients with IgA nephropathy are variable and depend on
      the renal function, blood pressure, status of urine proteins and the renal
      histological grade, and 2) especially female patients of childbearing age with
      hypertension need to be carefully examined to determine the cause of hypertension
      to avoid damage to target organs and complications during pregnancy.

PMID- 29642220
TI  - Clinical feature of infertile men carrying balanced translocations involving
      chromosome 10: Case series and a review of the literature.
AB  - RATIONALE: Infertile male carrying balanced translocations can be broadly divided
      into two types: pregestational and gestational infertility. Chromosome and
      breakpoints involved translocation should be considered in genetic counselling
      for these patients. To date, > 100 cases have been described with carrying
      balanced translocations involving chromosome 10 in fertile male. PATIENT
      CONCERNS: We report 11 cases translocation carriers involving chromosome 10, and
      review 99 carriers of chromosome 10 translocation from reported literature.
      DIAGNOSES: Eleven cases of chromosomal translocation were diagnosed by
      cytogenetic analysis. Three of these men had azoospermia or oligozoospermia,
      while eight had normal semen. Of these latter cases, their partners were able to
      conceive, but had a tendency to miscarry or have a stillbirth. INTERVENTIONS:
      Chromosome breakpoints should be considered in genetic counseling.
      Preimplantation genetic diagnosis should be performed to decrease the high risk
      of miscarriage and to minimize the genetic risks to offspring for patients with
      gestational infertility. OUTCOMES: The most common translocations and breakpoints
      were at t(4;10) and 10q24, observed in 12 and 10 patients respectively.
      Breakpoints at 10p15.1, 10p12, 10q10, 10q22.1, 10q24.2, and 10q26.3 were linked
      to pregestational infertility; breakpoints at 10p12.1, 10q11, 10q21.2, and
      10q23.3 were associated with gestational infertility; the other breakpoints were
      connected with both forms of infertility. LESSONS: Breakpoints at 10p12 and
      10q26.3 were associated with pregestational infertility. Other breakpoints at
      chromosome 10 were correlated with gestational infertility. These breakpoints
      should be considered when counseling men with chromosome 10 translocations should
      be informed of their options.

PMID- 29642223
TI  - A gastrointestinal stromal tumor with acute bleeding: Management and nursing:
      Erratum.

PMID- 29642222
TI  - Management of pulmonary embolism after recent intracranial hemorrhage: A case
      report.
AB  - RATIONALE: Venous thromboembolism may result from prolong immobilization
      following intracerebral hemorrhage. Massive pulmonary embolism with associated
      right heart failure is life-threatening, requiring treatment with anticoagulants
      or even thrombolytic agents. However, these drugs are contraindicated after a
      recent hemorrhagic episode, as they may induce further hemorrhage. There are no
      guidelines for treatment in these circumstances. PATIENT CONCERNS: A 57-year-old
      man experienced massive pulmonary embolism and shock 18 days after an
      intracerebral hemorrhage. DIAGNOSES: Tachycardia and high D-dimer (21.27 mg/L
      fibrinogen-equivalent units) were noted. Chest computed tomography showed
      bilateral pulmonary trunk embolism. INTERVENTIONS: Heparinization were used and
      activated partial thromboplastin time therapeutic range was 50 to 70 seconds.
      Fortunately, shock status and shortness of breath improved two days later.
      Continuing high dose Rivaroxaban was administrated for three weeks. OUTCOMES:
      There was no recurrent intracranial hemorrhage (ICH) following treatment for
      three-weeks with high-dose and one-year with standard dose of rivaroxaban. This
      report presents a treatment option in the management of these difficult clinical
      situations. LESSONS: The combination of unfractionated heparin infusion and
      continuing non-Vitamin K antagonist oral anticoagulants use could manage life
      threatening pulmonary embolism following recent ICH. Theoretically, the use of
      NOAC is a safer strategy if the patient with previous history of major ICH.

PMID- 29642225
TI  - A case report of Brugada-like ST-segment elevation probably due to coronary
      vasospasm: Erratum.

PMID- 29642224
TI  - Bedside ultrasound diagnosis of a malpositioned central venous catheter: A case
      report.
AB  - RATIONALE: Central venous catheter (CVC) placement is commonly performed in
      intensive care unit. And CVC placement is associated with risks including CVC
      malposition, pneumothorax. Many of the previously reported cases are about
      catheter misplacement detected by bedside ultrasound, chest x-ray (CXR) and
      computed tomography. In this case, malposition was detected by bedside ultrasound
      incidentally particularly with no clinical manifestation. PATIENT CONCERNS: An 88
      year-old male with severe diabetic peripheral neuropathy secondary to type 2
      diabetes mellitus was admitted for further treatment. DIAGNOSES: We cannulated a
      single-lumen CVC via the right subclavian vein, and the tip ended up in the
      internal jugular vein on the same side. With bedside ultrasound, we discovered
      the malposition though it was mistaken by aspiration of venous blood. Later, CXR
      revealed malposition of the tip once again. INTERVENTIONS: Since the patient was
      asymptomatic and the catheter was functioning normally, the catheter was used for
      the following 20 days without complications. Ultimately, we carefully performed
      the catheter removal. OUTCOMES: After the inserted catheter was removed, we
      attempted a new CVC through the left internal jugular vein. After the procedure,
      bedside ultrasound and CXR confirmed the correct position of CVC. Following
      successful replacement of the central catheter, no further complications were
      observed. LESSONS: Bedside ultrasound offers safety and effectiveness during
      insertion of CVC. It also exhibits promptness and accuracy compared to post
      intervention radiological imaging.

PMID- 29642226
TI  - Clinical features and prognosis of paraquat poisoning in French Guiana: A review
      of 62 cases.
AB  - Paraquat is a nonselective contact herbicide of great toxicological importance,
      being associated with high mortality rates. Because of its high toxicity, the
      European Union withdrew it from its market in 2007. The aim of this study is to
      analyze all cases of paraquat poisoning hospitalized in French Guiana in order to
      assess their incidence and main characteristics.Medical records of all paraquat
      intoxicated patients hospitalized from 2008 until 2015 were reviewed in this
      retrospective study.Demographics, clinical presentation, and laboratory data were
      evaluated.A total of 62 cases were reviewed. The incidence of paraquat poisoning
      was 3.8/100,000 inhabitants/year. There were 44 adults and 18 children younger
      than 16 years of age. The median ages were 31 years [18.08-75.25] in adults and
      13.4 years [0.75-15.08] in children, respectively. The median duration of
      hospitalization was longer in children [15.5 days (1-24)] than in adults [2 days
      (1-30)], P < .01. The majority of cases was due to self-poisoning (84%).Children
      had ingested a lower quantity of paraquat [48.8 mg/kg (10-571.1)] than adults
      [595.8 mg/kg (6-3636.4), P = .03]. There were more deaths among adults (65%) than
      in children (22%), P = .004. The severity and outcome was determined primarily by
      the amount of paraquat ingested.In conclusion, French Guiana has the largest
      cohort of paraquat poisonings in the European Union. The major factor affecting
      the prognosis of patients was the ingested amount of paraquat. The administration
      of activated charcoal or Pemba, in situ, within the first hour after ingestion of
      paraquat is essential.

PMID- 29642228
TI  - An observational study of clinical outcomes of everolimus-eluting bioresorbable
      scaffolds comparing the procedural use of optical coherence tomography against
      angiography alone.
AB  - OBJECTIVES: The introduction of the bioresorbable vascular scaffold (BVS) has led
      to new avenues of coronary intervention; however, there have been concerns raised
      regarding the mechanical properties of BVS and the resulting in-stent thrombosis.
      We aim to assess whether intracoronary imaging improves outcome in patients
      following BVS implantation. PATIENTS AND METHODS: All patients undergoing
      percutaneous coronary intervention using BVS at a single centre between June 2013
      and June 2016 were included in this study (n=79). Percutaneous coronary
      intervention with BVS was performed according to conventional practice:
      predilatation, postdilatation and intracoronary assessment with optical coherence
      tomography (OCT) according to operator's preferences. The primary endpoint was
      Major Adverse Cardiovascular Events (MACE), defined as all-cause mortality,
      myocardial infarction and revascularization, at 120 days. RESULTS: Forty-three
      (54.4%) patients underwent OCT assessment and 36 (45.6%) patients underwent
      angiography alone post-BVS insertion. There were no significant differences at
      baseline between both groups; a total of 13 (30.2%) patients who had
      intracoronary OCT imaging performed underwent further postdilatation after
      malapposed struts were identified. Although no deaths were observed, there was a
      significant difference seen in MACE over the follow-up period between OCT and
      angiography cohorts (4.7 vs. 19.4% respectively; P=0.042). There was a greater
      number of MACE in low-experienced operators. CONCLUSION: As visual assessment
      with angiography has poor specificity for identifying strut malapposition,
      intracoronary OCT should be undertaken in all patients postinsertion of BVS
      stents in inexperienced operators to appropriately assess for stent
      malapposition, and reduce the subsequent risk of MACE.

PMID- 29642229
TI  - Military Supplement: Perfluorocarbon Emulsions, Platelet Counts and Inflammation.
AB  - Perfluorocarbon emulsions (PFC) are a class of lipid coated micelle slurries
      wherein the active center of the micelle is a completely halogen/fluorine
      substituted hydrocarbon capable of dissolving very large quantities of non-polar
      gases. Due to their unique enhanced solubility for oxygen (O2) and nitrogen (N2)
      PFCs have been utilized in research as enhanced gas transport media for
      situations wherein the microcirculation is dysfunctional. In the early 1990's a
      PFC emulsion was approved for human use during coronary artery angioplasty and
      one is presently in use in Russia as well as other countries. The pharmaceutical
      class has had reported in the past associated with variable amounts of time
      limited thrombocytopenia. Anxiety about cerebral embolism surfaced after a
      pivotal phase III trial leading to the cessation of all human research in the
      United States. At that time papers both published and submitted to the FDA opined
      (without proof) that the platelet count decrease might be caused by platelet
      white cell conjugates and/or platelet aggregates thereby signaling a general
      inflammatory response to PFCs and a potential thrombosis risk. Although
      thrombocytopenia has been reported in response to PFC emulsion formulations it is
      not ubiquitous and seems to be less associated with some formulations. As well,
      in some recent animal studies there is no evidence of platelet white cell adverse
      interactions. The mechanism for the reported thrombocytopenia is as yet not fully
      understood, and risk-benefit profiles will have to be carefully studied as
      contemporary human trials move forward.

PMID- 29642227
TI  - Metabolic syndrome and risk of stroke: Protocol for an update systematic review
      and meta-analysis.
AB  - INTRODUCTION: The metabolic syndrome is composed of several cardiovascular risk
      factors and has a high prevalence throughout the world. However, there are no
      systematic analyses or well-conducted meta-analyses to evaluate the relationship
      between metabolic syndrome and stroke. The aim of this study is to examine this
      association of metabolic syndrome with stroke in different ages and sex. METHODS
      AND ANALYSIS: The update systematic review and meta-analysis will be conducted
      using published studies that will be identified from electronic databases (i.e.,
      PubMed, EMBASE, Web of Science, and Google Scholar. Studies that examined the
      association between metabolic syndrome and stroke, had a longitudinal or
      prospective cohort design, were conducted among in adults aged 40 to 70 years,
      provided sufficient data for calculating ORs or relative risk with a 95% CI, were
      published as original articles written in English or other languages, and have
      been published until December 2017 will be included. Study selection, data
      collection, quality assessment, and statistical syntheses will be conducted based
      on discussions among investigators. ETHICS AND DISSEMINATION: Ethics approval was
      not required for this study because it was based on published studies. The
      results and findings of this study will be submitted and published in a
      scientific peer-reviewed journal. The findings from this study could be useful
      for assessing metabolic syndrome risk factors in stroke, and determining
      approaches for prevention of stroke in the future.

PMID- 29642230
TI  - Mirna-Mediated Mechanisms of Cardiac Protection in Ischemic and Remote Ischemic
      Preconditioning - A Qualitative Systematic Review.
AB  - BACKGROUND: Ischemic preconditioning (IPC) and remote ischemic preconditioning
      (RIPC) protect myocardial tissue against subsequent ischemia and reperfusion
      injury (IRI) and have a high potential to improve patient outcome. The mediators
      and mechanisms of protection through IPC and RIPC remain largely unknown, but
      micro-RNAs (miRNAs) are promising candidates. METHODS: Systematic review of
      Medline and Embase databases for biomedical scientific literature. RESULTS: 26
      relevant publications (21 full-text original articles and 5 conference abstracts)
      were identified, 8 describing cell culture experiments, 14 animal experiments and
      4 randomised clinical trials in humans. Most commonly reported miRNAs with
      differential expression between preconditioned and control groups include miR-1,
      miR-21 and miR-144. Experimental designs and procedures differ widely, thereby
      limiting the potential to compare results between studies. Two of the four RCTs
      did not find any differentially expressed miRNAs. CONCLUSIONS: Results from RCTs
      should feed back into basic research and focused studies confirming or rejecting
      hypotheses generated by these RCTs are needed.

PMID- 29642231
TI  - Soluble Suppression of Tumorigenicity-2 Predicts Hospital Mortality in Burn
      Patients: An Observational Prospective Cohort Pilot Study.
AB  - BACKGROUND: The IL33/ST2 pathway has been implicated in the pathogenesis of
      different inflammatory diseases. Our aim was to analyze whether plasma levels of
      biomarkers involved in the IL33/ST2 axis might help to predict mortality in burn
      patients. METHODS: Single-center prospective observational cohort pilot study
      performed at the Burns Unit of the Plastic and Reconstructive Surgery Department
      of the Vall d'Hebron University Hospital (Barcelona). All patients aged >=18
      years old with second or third-degree burns requiring admission to the Burns Unit
      were considered for inclusion. Blood samples were taken to measure levels of
      interleukins (IL)6, IL8, IL33, and soluble suppression of tumorigenicity-2 (sST2)
      within 24 h of admission to the Burns Unit and at day 3. Results are expressed as
      medians and interquartile ranges or as frequencies and percentages. RESULTS:
      Sixty-nine patients (58 [84.1%] male, mean age 52 [35-63] years, total body
      surface area burned 21% [13%-30%], Abbreviated Burn Severity Index 6 [4-8]) were
      included. Thirteen (18.8%) finally died in the Burns Unit. Plasma levels of sST2
      measured at day 3 after admission demonstrated the best prediction accuracy for
      survival (area under the ROC curve 0.85 [0.71-0.99]; P < 0.001). The best cutoff
      point for the AUROC index was estimated to be 2,561. In the Cox proportional
      hazards model, after adjusting for potential confounding, a plasma sST2 level
      >=2,561 measured at day 3 was significantly associated with mortality (HR 6.94
      [1.73-27.74]; P = 0.006). CONCLUSIONS: Plasma sST2 at day 3 predicts hospital
      mortality in burn patients.

PMID- 29642232
TI  - Transcription factor 7 functions as an unfavorable prognostic marker of
      glioblastoma multiforme by promoting proliferation by upregulating c-Myc.
AB  - Transcription factor 7 (TCF7) is an oncogenic transcription factor in several
      kinds of cancers. However, the clinical significance of TCF7 in glioblastoma
      multiforme (GBM) has not been well elucidated. A total of 107 patients with
      surgical resection of GBM were enrolled in our study. TCF7 expression in these
      cases was detected by immunohistochemistry and the difference in TCF7 mRNA levels
      between tumor tissues and adjacent tissues was compared with a real-time PCR. The
      correlation between TCF7 expression and the clinicopathologic factors was
      analyzed using the chi-test. Moreover, the prognostic value of TCF7 was evaluated
      by univariate and multivariate analyses. In addition, the influence of TCF7 on
      the proliferation of the GBM cell line U251 was detected using an MTT assay after
      regulating TCF7 and its target gene c-Myc. The high and low expressions of TCF7
      accounted for 54.21 and 45.79%, respectively, in all cases. The mRNA level of
      TCF7 in GBM tissues was markedly higher than that in adjacent tissues, indicating
      the oncogenic role of TCF7 in GBM. High expression of TCF7 was associated
      significantly with high Ki67 percentage and the sex of the patients, and it was
      identified as an independent prognostic factor for patients with GBM. With
      experiments in vitro, TCF7 was shown to promote cell proliferation by increasing
      c-Myc expression in GBM. TCF7 could be considered an independent prognostic
      factor in GBM, and could enhance GBM cell proliferation by upregulating c-Myc,
      indicating that it may be a potential and promising molecular drug target for
      GBM.

PMID- 29642233
TI  - Sender and Receiver Acceptability and Usability of an Online Partner Notification
      Tool for Sexually Transmitted Infection in the Netherlands.
AB  - Users (index patients with a verified sexually transmitted infection and notified
      partners) rated the health care provider-initiated Internet-based partner
      notification application Suggestatest.nl acceptable and usable. Both groups were
      less positive about Suggestatest.nl to notify/get notified of HIV than other
      sexually transmitted infection. An anonymous notification was perceived less
      acceptable.

PMID- 29642234
TI  - A retrospective investigation of HLA-B*5801 in hyperuricemia patients in a Han
      population of China.
AB  - BACKGROUND: Hyperuricemia and gout have become increasingly prevalent in China.
      Allopurinol is an effective urate-lowering therapy, but it has severe side
      effects. HLA-B*5801 is highly associated with the allopurinol-induced toxic
      epidermal necrolysis and Stevens-Johnson syndrome. PATIENTS AND METHODS: In this
      retrospective report, we had genotyped HLA-B*5801 in 253 cases of hyperuricemia
      and gout patients in a Han population in Shenzhen and analyzed the clinical
      management of medications. RESULTS: We found 30 carriers of the HLA-B*5801 allele
      in 253 cases of hyperuricemia or gout patients in the population (11.9%).
      Allopurinol was prescribed in both HLA-B*5801-positive and HLA-B*5801-negative
      groups. The evaluation of four models with or without genetic screening and
      management of allopurinol or febuxostat indicated that the HLA-B*5801 screening
      had significant cost benefit for clinical management. CONCLUSION: For appropriate
      management and cost-effectiveness, the HLA-B*5801 allele should be screened in
      all patients with hyperuricemia and gout in the Chinese population.

PMID- 29642235
TI  - Back to Living: Long-term Functional Status of Pediatric Patients Who Completed
      Intensive Interdisciplinary Pain Treatment.
AB  - OBJECTIVES: To provide a descriptive account of long-term functioning (>=5 y
      posttreatment) among youth who completed intensive interdisciplinary pain
      treatment (IIPT) for pediatric chronic pain conditions. MATERIALS AND METHODS: A
      total of 95 patients (mean age at follow-up=20.0 y) treated at least 5 years
      previously at a single IIPT program completed questionnaires assessing pain,
      functional disability, health care utilization, academic/career achievement, and
      quality of life. Data analyses focused on pain, functioning, and progress toward
      developmental goals at long-term follow-up. RESULTS: The majority of respondents
      report significant reduction in pain compared with preadmission (P<0.001). Five
      years posttreatment, average functional disability scores were in the minimal
      range, with statistically significant decrease in functional disability from time
      of admission (P<0.001). Nearly 80% of respondents characterized themselves as
      having no functional difficulties at follow-up. Clinically significant
      improvement was established for both pain and function. Respondents generally
      reported developmentally appropriate status, with 89% graduating high school on
      schedule. DISCUSSION: Results show long-term positive functioning among
      individuals who underwent intensive rehabilitation treatment for chronic pain as
      children or adolescents. Despite experiencing one or more pain flares at some
      point after treatment, most former IIPT patients report minimal to no ongoing
      functional disability, complete or partial resolution of pain symptoms, and
      developmentally appropriate progress toward goals (eg, school completion,
      independent living).

PMID- 29642236
TI  - Occupational and Ergonomic Factors Associated With Low Back Pain Among Car-patrol
      Police Officers: Findings From the Quebec Serve and Protect Low Back Pain Study.
AB  - OBJECTIVES: Low back pain (LBP) is frequent and burdensome among police officers,
      but occupational and ergonomic factors associated with LBP and its chronic
      symptoms have never been studied among these workers using a biopsychosocial
      model. This study aimed at exploring such factors associated with acute or
      subacute LBP and chronic low back pain (CLBP) among car-patrol police officers.
      METHODS: A web-based cross-sectional study was conducted among car-patrol
      officers working in the province of Quebec (Canada). Factors associated with
      acute or subacute LBP and CLBP (as opposed to absence of LBP) were studied using
      a multivariate multinomial regression model. RESULTS: A total of 2208 car-patrol
      officers composed the study population. Statistically significant
      occupational/ergonomic determinant for higher prevalence of acute or subacute LBP
      was more frequent discomfort in the lower back when sitting in the patrol car as
      a driver (adjusted odds ratio [OR], 3.008; 95% confidence interval [CI], 2.170
      4.168). More frequent posttraumatic interventions was associated with lower
      prevalence of acute or subacute LBP (adjusted OR, 0.609; 95% CI, 0.410-0.907).
      Occupational and ergonomic factors associated with higher prevalence of CLBP were
      greater seniority (adjusted OR, 1.061; 95% CI, 1.007-1.118) and more frequent
      discomfort in the lower back when sitting in the patrol car as a driver (adjusted
      OR, 7.546; 95% CI, 5.257-10.831). DISCUSSION: Few occupational and ergonomic
      factors that police organizations could use to better tailor prevention were
      found to be associated with acute or subacute LBP and CLBP. This cross-sectional
      study is an efficient first investigation for screening hypotheses that should be
      confirmed in further cohort studies.

PMID- 29642238
TI  - ASSOCIATION BETWEEN GENOTYPE AND DISEASE PROGRESSION IN ITALIAN STARGARDT
      PATIENTS: A Retrospective Natural History Study.
AB  - PURPOSE: To investigate the natural history of Stargardt disease over a multiyear
      follow-up. METHODS: We reviewed medical records of Stargardt disease patients,
      with clinical diagnosis of Stargardt disease at a single institution, which was
      also supported by molecular diagnosis. All patients underwent best-corrected
      visual acuity, fundus photography, optical coherence tomography, and full-field
      electroretinography. RESULTS: The study cohort consisted of 157 Stargardt disease
      patients aged 30.4 +/- 1.1 years. Longitudinal analysis (mean follow-up: 3 years)
      showed a significant worsening of best-corrected visual acuity at an average rate
      of 1.5 Early Treatment Diabetic Retinopathy Study letters/year (P < 0.001), an
      enlargement of retinal pigment epithelium lesion area by optical coherence
      tomography at an average linear rate of 0.10 mm/year (P < 0.001), and a thinning
      of central macular thickness at a mean rate of -1.42 MUm/year (P < 0.001).
      Survival analysis showed that patients with 2 alleles harboring likely-null
      variants, on average, reached most severe disease stage, i.e., legal blindness,
      alteration in both dark-adapted and light-adapted electroretinographic responses,
      and retinal pigment epithelium lesion area larger than 2.5 mm significantly
      earlier than patients with at least one allele harboring a missense variant.
      CONCLUSION: The current longitudinal study showed a significant genotype
      phenotype correlation characterization, because patients harboring 2 likely-null
      alleles reach a severe disease stage about 10 years earlier than patients with at
      least one missense allele.

PMID- 29642237
TI  - Association Between the 2011 Fibromyalgia Survey Criteria and Multisite Pain
      Sensitivity in Knee Osteoarthritis.
AB  - OBJECTIVES: The present study evaluated the relationship between the 2011
      American College of Rheumatology fibromyalgia (FM) survey criteria and
      quantitative sensory testing (QST). MATERIALS AND METHODS: Patients with knee
      osteoarthritis scheduled to undergo knee arthroplasty completed the FM survey
      criteria and self-report measures assessing clinical symptoms. Patients also
      underwent a battery of QST procedures at the surgical knee and remote body sites,
      including pressure algometry, conditioned pain modulation, and temporal
      summation. All assessments were completed before surgery. FM survey criteria were
      used to calculate a continuous FM score indicating FM severity. RESULTS: A total
      of 129 patients were analyzed. Of these, 52.7% were female, 93.8% were Caucasian,
      and 3.8% met the FM survey criteria for FM classification. Mean age for females
      (63.6 y) and males (64.7 y) was similar. Females and males differed significantly
      in nearly every outcome, including FM severity, clinical pain, anxiety,
      depression, and pressure pain sensitivity. In females, FM scores significantly
      correlated with pressure pain sensitivity, but not conditioned pain modulation or
      temporal summation, such that increased sensitivity was associated with greater
      FM severity at all body sites examined. In addition, as FM scores increased, the
      association between pain sensitivity at the surgical knee and pain sensitivity at
      remote body sites also increased. No relationship between FM score and QST was
      observed in males. DISCUSSION: We demonstrated an association between diffuse
      hyperalgesia as measured by QST and FM severity in females with knee
      osteoarthritis. These results suggest that the FM survey criteria may represent a
      marker of pain centralization in females with potential utility in clinical
      decision making.

PMID- 29642239
TI  - MULTILEVEL ISCHEMIA IN DISORGANIZATION OF THE RETINAL INNER LAYERS ON PROJECTION
      RESOLVED OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.
AB  - PURPOSE: To examine the relationship between ischemia and disorganization of the
      retinal inner layers (DRIL). METHODS: Cross-sectional retrospective study of 20
      patients (22 eyes) with diabetic retinopathy presenting to a tertiary academic
      referral center, who had DRIL on structural optical coherence tomography (OCT)
      using Spectralis HRA + OCT (Heidelberg Engineering, Heidelberg, Germany) and OCT
      angiography with XR Avanti (Optovue Inc, Fremont, CA) on the same day. Optical
      coherence tomography angiography images were further processed to remove flow
      signal projection artifacts using a software algorithm adapted from recent
      studies. Retinal capillary perfusion in the superficial capillary plexuses,
      middle capillary plexuses, and deep capillary plexuses, as well as integrity of
      the photoreceptor lines on OCT was compared in areas with DRIL to control areas
      without DRIL in the same eye. RESULTS: Qualitative assessment of projection
      resolved OCT angiography of eyes with DRIL on structural OCT demonstrated
      significant perfusion deficits compared with adjacent control areas (P < 0.001).
      Most lesions (85.7%) showed superimposed superficial capillary plexus and/or
      middle capillary plexus nonperfusion in addition to deep capillary plexus
      nonflow. Areas of DRIL were significantly associated with photoreceptor
      disruption (P = 0.035) compared with adjacent DRIL-free areas. CONCLUSION: We
      found that DRIL is associated with multilevel retinal capillary nonperfusion,
      suggesting an important role for ischemia in this OCT phenotype.

PMID- 29642241
TI  - Modeling the Nature of Grammar and Vocabulary Trajectories From Prekindergarten
      to Third Grade.
AB  - Purpose: This study investigated the longitudinal development of 2 important
      contributors to reading comprehension, grammar, and vocabulary skills. The
      primary interest was to examine the trajectories of the 2 skill areas from
      preschool to 3rd grade. Method: The study involved a longitudinal sample of 420
      children from 4 sites. Language skills, including grammar and vocabulary, were
      assessed annually with multiple measures. Multivariate latent growth curve
      modeling was used to examine the developmental trajectories of grammar and
      vocabulary, to test the correlation between the 2 domains, and to investigate the
      effects of demographic predictors on language growth. Results: Results showed
      that both grammar and vocabulary exhibited decelerating growth from preschool to
      Grade 2. In Grade 3, grammar growth further flattened, whereas vocabulary
      continued to grow stably. Growth of vocabulary and grammar were positively
      correlated. Demographic characteristics, such as child gender and family
      socioeconomic status, were found to predict the intercept but not the slope of
      the growth trajectories. Conclusions: Children's growth in grammar skills is
      differentiated in a number of important ways from their growth in vocabulary
      skills. Results of this study suggest the need to differentiate these dimensions
      of language when seeking to closely examine growth from preschool to primary
      grades.

PMID- 29642242
TI  - Shikonin Prevents Early Phase Inflammation Associated with Azoxymethane/Dextran
      Sulfate Sodium-Induced Colon Cancer and Induces Apoptosis in Human Colon Cancer
      Cells.
AB  - Shikonin is the main active principle in the root of Lithospermum erythrorhizon,
      widely used in traditional Chinese medicine for its anti-inflammatory and wound
      healing properties. Recent research highlights shikonin's antitumor properties
      and capacity to prevent acute ulcerative colitis. The aim of the present study
      was to evaluate the ability of shikonin to prevent, in vivo, the early phases of
      colorectal cancer development, with special focus on its cytotoxic mechanism in
      vitro. We employed the azoxymethane/dextran sulfate sodium model of colitis in
      Balb/C mice. Body weight and drinking were monitored throughout the experiment,
      and length of colon and lesions of the colon were recorded on termination of the
      experiment in all of the experimental groups. Colons underwent histological
      evaluation and biochemical analyses [myeloperoxidase activity assay, measurement
      of interleukin-6, evaluation of proinflammatory enzymes (cyclooxygenase-2 and
      inducible nitric oxide synthase), and nuclear factor-kappaB activation by Western
      blot]. Caco-2 cells were used to evaluate, in vitro, the effect of shikonin on
      proliferation, cytotoxicity, cell cycle, and apoptosis. Our results reveal that
      shikonin significantly protected the intestinal tissue of our animals by
      preventing the shortening of the colorectum and ulcer formation in a dose
      dependent manner. Shikonin attenuated the expression of cyclooxygenase-2 and
      inducible nitric oxide synthase, and myeloperoxidase activity, and inhibited the
      production of interleukin-6 and activation of nuclear factor-kappaB. It induced
      Bcl-2 and inhibited caspase 3. In conclusion, shikonin acts as a chemopreventive
      agent in the azoxymethane/dextran sulfate sodium model through inhibition of the
      proinflammatory milieu generated during the disease, an important risk factor in
      cancer development.

PMID- 29642243
TI  - Symptomatic Ruptured Seed-Type Partial Ossification of the Ligamentum Flavum: A
      Case Report.
AB  - BACKGROUND:  Seed-type partial ossification of the ligamentum flavum (OLF)
      causing severe radiculopathy after rupture has not yet been described in the
      literature. CASE DESCRIPTION:  A 51-year-old man presented with sudden onset
      severe back pain and right anterior thigh pain without any neurologic deficit
      after lifting a heavy weight. On preoperative computed tomography, we identified
      a ruptured seed-type partial OLF at the L1-L2 level. T2-weighted magnetic
      resonance sagittal and axial images showed thecal sac compression by the ruptured
      OLF. There was no improvement in his symptoms after 2 weeks of conservative
      management. The patient had percutaneous full endoscopic interlaminar removal of
      OLF. Postoperatively he experienced prompt improvement of his symptoms.
      CONCLUSION:  Rupture of seed-type partial OLF causing severe radiculopathy is
      extremely rare, and percutaneous endoscopy is a safe and effective alternative to
      open surgery in selected cases.

PMID- 29642240
TI  - Sodium bicarbonate cotransporter NBCe2 gene variants increase sodium and
      bicarbonate transport in human renal proximal tubule cells.
AB  - RATIONALE: Salt sensitivity of blood pressure affects >30% of the hypertensive
      and >15% of the normotensive population. Variants of the electrogenic sodium
      bicarbonate cotransporter NBCe2 gene, SLC4A5, are associated with increased blood
      pressure in several ethnic groups. SLC4A5 variants are also highly associated
      with salt sensitivity, independent of hypertension. However, little is known
      about how NBCe2 contributes to salt sensitivity, although NBCe2 regulates renal
      tubular sodium bicarbonate transport. We hypothesized that SLC4A5 rs10177833 and
      rs7571842 increase NBCe2 expression and human renal proximal tubule cell (hRPTC)
      sodium transport and may be a cause of salt sensitivity of blood pressure.
      OBJECTIVE: To characterize the hRPTC ion transport of wild-type (WT) and
      homozygous variants (HV) of SLC4A5. METHODS AND RESULTS: The expressions of NBCe2
      mRNA and protein were not different between hRPTCs carrying WT or HV SLC4A5
      before or after dopaminergic or angiotensin (II and III) stimulation. However,
      luminal to basolateral sodium transport, NHE3 protein, and Cl-/HCO3- exchanger
      activity in hRPTCs were higher in HV than WT SLC4A5. Increasing intracellular
      sodium enhanced the apical location of NBCe2 in HV hRPTCs (4.24+/-0.35% to
      11.06+/-1.72% (P<0.05, N = 3, 2-way ANOVA, Holm-Sidak test)) as determined by
      Total Internal Reflection Fluorescence Microscopy (TIRFM). In hRPTCs isolated
      from kidney tissue, increasing intracellular sodium enhanced bicarbonate
      dependent pH recovery rate and increased NBCe2 mRNA and protein expressions to a
      greater extent in HV than WT SLC4A5 (+38.00+/-6.23% vs HV normal salt (P<0.01, N
      = 4, 2-way ANOVA, Holm-Sidak test)). In hRPTCs isolated from freshly voided
      urine, bicarbonate-dependent pH recovery was also faster in those from salt
      sensitive and carriers of HV SLC4A5 than from salt-resistant and carriers of WT
      SLC4A5. The faster NBCe2-specific bicarbonate-dependent pH recovery rate in HV
      SCL4A5 was normalized by SLC4A5- but not SLC4A4-shRNA. The binding of purified
      hepatocyte nuclear factor type 4A (HNF4A) to DNA was increased in hRPTCs carrying
      HV SLC4A5 rs7571842 but not rs10177833. The faster NBCe2-specific bicarbonate
      dependent pH recovery rate in HV SCL4A5 was abolished by HNF4A antagonists.
      CONCLUSION: NBCe2 activity is stimulated by an increase in intracellular sodium
      and is hyper-responsive in hRPTCs carrying HV SLC4A5 rs7571842 through an
      aberrant HNF4A-mediated mechanism.

PMID- 29642244
TI  - Adverse Cerebral Outcomes after Coronary Artery Bypass Surgery-More Than a Decade
      of Experience in a Single Center.
AB  - BACKGROUND: Nonfatal strokes, transient ischemic attacks (TIAs), and reversible
      ischemic neurological deficits (RIND) after elective coronary artery bypass
      grafting (CABG) are devastating clinical problems. The anesthesiologist, surgical
      and intensive care teams in a community hospital adopted a strategy developed in
      an effort to minimize these adverse outcome events.The purpose of this study is
      to determine the incidence of and predictors for perioperative adverse neurologic
      events. METHODS: A historical cohort study of 1,108 consecutive CABG patients
      operated between 2002 and 2014. Outcomes were defined as (1) a new neurologic
      damage (a new stroke, TIA, or RIND) and (2) a new neurologic damage or 30 days
      mortality. RESULTS: Adverse cerebral outcomes occurred in 16 patients (1.4
      percent). Nine patients had postoperative stroke, six suffered TIAs, and one had
      postoperative RIND.In multivariate analysis, older age (OR 1.07, 95% CI 1.01
      1.14), congestive heart failure (OR 3.57, 95% CI 1.22-10.49) and prior stroke (OR
      6.27, 95% CI 1.78-22.03) were significantly associated with increased risk of new
      neurologic damage. These parameters were also significantly associated with
      increased risk of the combined outcome (new neurologic damage/mortality).
      CONCLUSIONS: A low incidence rate of adverse cerebral outcomes after CABG in
      community hospital can be achieved with the use of the suggested surgical
      intensive care, and anesthetic strategy. Advanced age, congestive heart failure,
      and prior stroke are associated with adverse outcomes.

PMID- 29642245
TI  - Impact of Glucose Metabolism Disorders on IGF-1 Levels in Patients with
      Acromegaly.
AB  - In this study, we aimed to evaluate the presence of glucose metabolism
      abnormalities and their impact on IGF-1 levels in patients with acromegaly.
      Ninety-three patients with acromegaly (n=93; 52 males/41 females) were included
      in this study. Patients were separated into three groups such as; normal glucose
      tolerance (n=23, 25%), prediabetes (n=38, 41%), and diabetes mellitus (n=32,
      34%). Insulin resistance was calculated with homeostasis model assessment (HOMA).
      HOMA-IR > 2.5 or <=2.5 were defined as insulin resistant or noninsulin resistant
      groups, respectively. Groups were compared in terms of factors that may be
      associated with glucose metabolism abnormalities. IGF-1% ULN (upper limit of
      normal)/GH ratios were used to evaluate the impact of glucose metabolism
      abnormalities on IGF-1 levels. Patients with diabetes mellitus were significantly
      older with an increased frequency of hypertension (p<0.001, p=0.01,
      respectively). IGF-1% ULN/GH ratio was significantly lower in prediabetes group
      than in normal glucose tolerance group (p=0.04). Similarly IGF-1% ULN/GH ratio
      was significantly lower in insulin resistant group than in noninsulin resistant
      group (p=0.04). Baseline and suppressed GH levels were significantly higher in
      insulin resistant group than in noninsulin resistant group (p=0.024, p<0.001,
      respectively). IGF-1% ULN/GH ratio is a useful marker indicating glucose
      metabolism disorders and IGF-1 levels might be inappropriately lower in
      acromegalic patients with insulin resistance or prediabetes. We suggest that IGF
      1 levels should be re-evaluated after the improvement of insulin resistance or
      glycemic regulation for the successful management of patients with acromegaly.

PMID- 29642246
TI  - A Novel CCND2 Mutation in a Previously Reported Case of Megalencephaly and
      Perisylvian Polymicrogyria with Postaxial Polydactyly and Hydrocephalus.

PMID- 29642248
TI  - ?

PMID- 29642247
TI  - Examining Workflow in a Pediatric Emergency Department to Develop a Clinical
      Decision Support for an Antimicrobial Stewardship Program.
AB  - BACKGROUND:  Clinical decision support (CDS) embedded into the electronic health
      record (EHR), is a potentially powerful tool for institution of antimicrobial
      stewardship programs (ASPs) in emergency departments (EDs). However, design and
      implementation of CDS systems should be informed by the existing workflow to
      ensure its congruence with ED practice, which is characterized by erratic
      workflow, intermittent computer interactions, and variable timing of antibiotic
      prescription. OBJECTIVE:  This article aims to characterize ED workflow for four
      provider types, to guide future design and implementation of an ED-based ASP
      using the EHR. METHODS:  Workflow was systematically examined in a single,
      tertiary-care academic children's hospital ED. Clinicians with four roles
      (attending, nurse practitioner, physician assistant, resident) were observed over
      a 3-month period using a tablet computer-based data collection tool. Structural
      observations were recorded by investigators, and classified using a predetermined
      set of activities. Clinicians were queried regarding timing of diagnosis and
      disposition decision points. RESULTS:  A total of 23 providers were observed for
      90 hours. Sixty-four different activities were captured for a total of 6,060
      times. Among these activities, nine were conducted at different frequency or time
      allocation across four roles. Moreover, we identified differences in sequential
      patterns across roles. Decision points, whereby clinicians then proceeded with
      treatment, were identified 127 times. The most common decision points identified
      were: (1) after/during examining or talking to patient or relative; (2) after
      talking to a specialist; and (3) after diagnostic test/image was resulted and
      discussed with patient/family. CONCLUSION:  The design and implementation of CDS
      for ASP should support clinicians in various provider roles, despite having
      different workflow patterns. The clinicians make their decisions about treatment
      at different points of overall care delivery practice; likewise, the CDS should
      also support decisions at different points of care.

PMID- 29642249
TI  - ?

PMID- 29642250
TI  - ?

PMID- 29642251
TI  - Terminal ileum resection as a trigger for Strongyloides stercoralis
      hyperinfection and ensuing serial sepsis in a 37-year-old patient with
      complicated Crohn's disease: a case report.
AB  - The nematode Strongyloides stercoralis, outside the tropics and subtropics
      present in small endemic foci, can cause an infection after direct skin contact
      with contaminated soil containing infective filariform larvae and, rarely, after
      intimate interhuman contact or after transplantation of an infected solid organ.
      Following skin penetration, migration, and maturation through several stages, a
      small number of invasive filariform larvae can develop anew in the gut lumen,
      perpetuating new cycles of penetration, tissue migration, and reproduction,
      without leaving the host.In a state of immunosuppression, autoinfection can
      progress to life-threatening hyperinfection and/or infection disseminated through
      virtually any organ. In developed countries, the most frequently recognized risk
      for severe hyperinfection is corticosteroid therapy, but this has been also
      described in malnourished, alcoholic, cancer, and transplant patients. Due to the
      frequent need for immunosuppressive therapy, patients suffering from inflammatory
      bowel disease (IBD) are susceptible to develop overwhelming strongyloidiasis.
      Strongyloidiasis can be easily overlooked in clinical settings, and in many
      European regions there is poor insight into the epidemiological burden of this
      disease.We present a case of S. stercoralis hyperinfection that triggered 3
      successive episodes of sepsis caused by pathogens of the gut flora in a young
      patient suffering from stenotic form of Crohn's disease. S. stercoralis
      hyperinfection occurred in the corticosteroid-free period, shortly after
      resection of the terminal ileum, which was probably the trigger for the
      overwhelming course. The patient was successfully treated with 10-day albendazole
      therapy.

PMID- 29642252
TI  - [ASCO- and ESMO-update 2017 - highlights of the 53. meeting of the American
      Society of Clinical Oncology/ASCO 2017 and European Society for Medical
      Oncology/ESMO congress 2017].
AB  - At ASCO 2017, and subsequently the ESMO congress 2017, a number of studies were
      presented which, in part, may change the present standard of therapy in
      gastrointestinal oncology. The German FLOT4 trial established perioperative
      Docetaxel, Oxaliplatin and 5-Fluorouracil (5-FU) as the new treatment standard
      for resectable adenocarcinoma of the gastroesophageal junction and the stomach.
      In hepatocellular carcinoma (HCC), two large studies did not show a survival
      benefit for selective internal therapy (SIRT), so an increasing use of SIRT in
      HCC is not recommended. On the other hand, the multityrosinekinase inhibitor
      Lenvatinib seems to be a promising alternative to sorafenib in first line
      treatment of metastatic HCC. In early colon cancer-following the data from the
      large IDEA initiative-three months of capecitabine and oxaliplatin is recommended
      for low-risk stage III cancers (T1 - 3, N1), while in high-risk stage III cancers
      (T4 or N2) patients should still receive six months of oxaliplatin and a
      fluoropyrimidine. Aside from regular exercise, one study found that regular
      intake of tree nuts (at least 2 servings per week), may decrease the risk of
      recurrence. In first line metastatic colorectal cancer (mCRC), SIRT should not be
      applied, whereas in BRAF mutant cancers, the combination of irinotecan, cetuximab
      and vemurafenib seems to be a promising second line treatment option. In biliary
      tract cancer, after curative resection, six months of capecitabine is considered
      the new treatment standard. Finally, in pancreatic cancer, targeting the tumor
      stroma with pegylated hyaluronidase (PEGPH20) may be a new treatment option that
      needs to be proven in phase 3 studies.

PMID- 29642253
TI  - [The IDEA Intergroup Study - New standard in adjuvant treatment of stage III
      colorectal cancer].

PMID- 29642254
TI  - [Colorectal cancer prevention in Europe - where do we stand?]

PMID- 29642255
TI  - [The School Entry Health Examination: A Critical View of History and Status Quo.]
AB  - At the end of the 19th century, the school entrance medical examination of all
      school beginners was established in Germany. The focus was on exclusion of
      infectious diseases and illnesses that could make school attendance more
      difficult or worsen during the school visit. In the middle of the 20th century
      the concept of "school maturity" came to the foreground. Different "school
      maturity concepts" were applied but abandoned because they could not withstand an
      evaluation. Meanwhile, the concept of "school maturity" has been replaced by the
      concept of "school ability". The question no longer arises as to whether or not a
      child can be taught at school, but rather the assistance and support with which
      this can be achieved. Today, the school entrance medical check-up in nearly all
      the federal states includes, in addition to a medical history, an assessment of
      the precautionary and vaccination status, a visual and hearing test as well as
      assessment of the development of the child and his/her individual support
      requirements, especially in the field of cognition and language. In almost all
      German federal states, the school entrance examinations use up considerable
      resources of the pediatric and adolescent services in the public health
      departments. In the paper presented, this is critically discussed, and a
      discourse is suggested as to whether these resources could be used more
      effectively in terms of child health considering changed social conditions, such
      as the mandatory health checks in childhood in many federal states, the increase
      of immigrants from other countries, in particular asylum seekers, or the
      "Inclusion", i. e. with closure of special-needs schools and the associated
      challenges in the regular schools.

PMID- 29642256
TI  - ?

PMID- 29642257
TI  - [Health Impact of the Heatwave of 2015: Hospital Admissions in Frankfurt/Main,
      Germany].
AB  - Heatwaves are gaining in importance due to increasing climatic changes. They can
      impair health and increase mortality. A comparison of studies is difficult
      because of differences in the definition of a heatwave used and/or different
      populations studied. In this study, morbidity data were collected using the web
      based IVENA system. This system registers hospital admissions with diagnosis by
      the emergency medical services. We analysed hospital admissions in Frankfurt/Main
      during June-August of 2014-2016. These periods included a heatwave in July 2015
      (per definition>32 degrees C for at least 5 days/more than 4 days). On days with
      "heatwave", there was a 22% increase in hospital admissions of patients brought
      in by the emergency services (excess morbidity). Considering only "heat-related
      diagnosis", the increase was 300%. In addition to the increase in hospital
      admissions on "heatwave" days, there was also a direct correlation between
      temperature and hospital admissions over the summer days. Using the data on
      hospital admission of patients brought in by the emergency services turned out to
      be a valid marker for "heat morbidity".

PMID- 29642258
TI  - [Rapidly Growing Tumor of the Eyelid].

PMID- 29642259
TI  - [Sun, Moon and Stars].

PMID- 29642260
TI  - [Endothelial Cell Reaction to Elevated Hydrostatic Pressure and Oxidative Stress
      in Vitro].
AB  - INTRODUCTION: Endothelial dysfunction has become a strongly discussed factor
      regarding glaucoma pathogenesis. In addition to peripapillary bleedings as signs
      of vascular damage, there is a definite correlation between glaucoma and vascular
      dysregulation syndrome. The aim of this study was to evaluate endothelial cell
      reaction to moderately elevated hydrostatic pressure and oxidative stress in
      vitro. METHODS: In vitro, primarily dissociated brain microvascular endothelial
      cells (BMECs) were exposed to moderately elevated hydrostatic pressure (60 and
      120 mmHg) in a special pressure chamber. Additionally, cells primarily exposed to
      pressure, and cells not exposed to pressure, were incubated with low amounts of
      H2O2. A live/dead assay was performed to evaluate cell viability.
      Immunohistochemical staining against actin was used for morphological evaluation.
      RESULTS: Neither 60 nor 120 mmHg of elevated pressure had a viability changing
      effect on primary endothelial cells. Secondary, no big morphological changes
      could be discovered. However, against a low concentration of oxidative stress,
      BMECs showed high vulnerability. A difference in reaction to cells stressed with
      high pressure before could not be shown. CONCLUSION: Direct effects, in terms of
      higher vulnerability or morphological changes of moderately elevated high
      pressure on endothelial cells, could not be shown. However, the reaction to low
      amounts of oxidative stress indicates the involvement of endothelial cells in the
      pathogenesis of glaucoma and the special role of oxidative stress when referring
      to endothelial dysfunction in glaucomatous disease.

PMID- 29642261
TI  - [Foster Modification of Full Tendon Transposition of Vertical Rectus Muscles for
      Sixth Nerve Palsy].
AB  - INTRODUCTION: Since 1907 a variety of muscle transposition procedures for the
      treatment of abducens nerve palsy has been established internationally. Full
      tendon transposition of the vertical rectus muscle was initially described by
      O'Connor 1935 and then augmented by Foster 1997 with addition of posterior
      fixation sutures on the vertical rectus muscle. Full tendon transposition
      augmented by Foster belongs to the group of the most powerful surgical techniques
      to improve the abduction. Purpose of this study was to evaluate the results of
      full tendon vertical rectus transposition augmented with lateral fixation suture
      for patients with abducens nerve palsy. METHODS AND RESULTS: Full tendon
      transpositions of vertical rectus muscles augmented with posterior fixation
      suture was performed in 2014 on five patients with abducens nerve palsy. Two of
      the patients received Botox injections in the medial rectus muscle: one of them
      three months after the surgery and another during the surgery. One of the
      patients had a combined surgery of the horizontal muscles one year before. On
      three of the patients, who received a pure transposition surgery, the
      preoperative deviation at the distance (mean: + 56.6 pd; range: + 40 to + 80 pd)
      was reduced by a mean of 39.6 pd (range 34 to 50 pd), the abduction was improved
      by a mean of 3 mm (range 2 to 4 mm). The other two patients, who received besides
      the transposition procedure additional surgeries of the horizontal muscles, the
      preoperative deviation at the distance (+ 25 and + 126 pd respectively) was
      reduced by 20 and 81 pd respectively. The abduction was improved by 4 and 8 mm
      respectively. After surgery two patients developed a vertical deviation with a
      maximum of 4 pd. None of the patients had complications or signs of anterior
      segment ischemia. The elevation and/or depression was only marginally affected.
      There was no diplopia in up- or downgaze. CONCLUSIONS: Full tendon transposition
      of vertical rectus muscles, augmented with lateral posterior fixation suture is a
      safe and effective treatment method for abducens nerve palsy and in most cases
      recession of the medial rectus can be avoided. Upgaze and downgaze are affected
      very slightly. Diverse studies have shown that the risk of anterior segment
      ischemia is low.

PMID- 29642262
TI  - [Predictive Value of OCT-Controlled Early Response of Macular Edema Secondary to
      Retinal Vein Occlusion After Intravitreal Bevacizumab Therapy].
AB  - INTRODUCTION: The goal of this study was to examine the response of macular edema
      (ME) secondary to retinal vein occlusion (RVO) to predict macular edema course
      and re-injection intervals. MATERIAL AND METHODS: Twenty-four eyes from 24
      patients with ME secondary to RVO, both central (CRVO) and branch (BRVO), were
      retrospectively included. All eyes received intravitreal bevacizumab therapy
      (1.25 mg/0.1 ml). Repetitive optical coherence tomography (OCT) examinations were
      performed to document the early macular edema response to treatment and the
      course of the disease during the first three monthly injections until the last
      follow-up 105 days after the first injection. RESULTS: A significant ME reduction
      is present as early as three hours after the first injection of bevacizumab. This
      significant reduction of central retinal thickness (CRT) is present until the
      third post-injection day. The greatest reduction occurs during the first 24
      hours. Patients who reach a CRT less than 300 um after 24 hours (day 1) have no
      recurrence after 30 days. Patients with a CRT over 300 um on day 1 have a 50%
      rate of recurrence after 30 days. The favorable results of the first group are
      still present during the last follow-up examination, 105 days after the first
      injection. DISCUSSION AND CONCLUSION: An OCT examination, 24 hours after the
      first bevacizumab injection, has a prognostic value and can identify the patients
      that can tolerate longer intervals between injections, this results in fewer
      bevacizumab injections during the course of the disease. This way an
      individualization of the treatment, opposed to a fixed therapy pattern, can be
      implemented. Also, patients with poor prognosis can be identified early and
      treatment can be altered or intensified accordingly.

PMID- 29642263
TI  - [Endogenous Endophthalmitis: Epidemiology, Clinic, Therapy and Visual Outcome].
AB  - BACKGROUND: Endogenous endophthalmitis is a rare and severe inflammation of the
      eye in the context of a systemic infectious disease, which can lead to the loss
      of the affected eye in the worst case. MATERIAL AND METHODS: In a 5-year period,
      20 eyes were treated for endogenous endophthalmitis and evaluated
      retrospectively. Evaluation parameters were epidemiological data, causes,
      concomitant diseases, assessment of the pathogen spectrum, therapy and visual
      acuity. RESULTS: 13.2% (n = 20/152; 20 eyes of 17 patients) of all
      endophthalmitis cases were of endogenous origin. In 15% (n = 3/20) of the cases,
      bilateral endogenous endophthalmitis was present. The cause for the
      endophthalmitis was generalised sepsis in 9 of 17 cases, an infection of the
      urogenital tract in 2 of 17 cases and endocarditis and liver abscess in 1 of 17
      cases, respectively. In 4 of 17 cases, no primary foci were detected. Eight of 17
      patients suffered from diabetes mellitus, 6 of 17 from renal insufficiency and 2
      of 17 from malignancies, pneumonia or rheumatism. Two of 17 patients had had an
      organ transplantation, 15 of 17 suffered from cardiovascular diseases, 3 of 17
      were immunosuppressed and 2 of 17 reported drug abuse. Four of 17 infections were
      caused by streptococci, 3 of 17 by Candida, 2 of 17 by herpes viruses and 1 of 17
      by Staphylococcus aureus and Bacillus cereus. No pathogen could be found in 5
      cases. The time interval between the onset of symptoms and diagnosis and the
      beginning of the therapy was 4 days (min.: 1 day; max.: 39 days). This was
      significantly longer in comparison with other causes of endophthalmitis (p <
      0.001). Median visual acuity (VA) was 2.0 logMAR (n = 19/20) at the first
      presentation. One month and three months after initiation of the therapy VA was
      1.3 logMAR (both n = 15/20), VA was 0.1 logMAR (n = 9/20) at the one year follow
      up. Retinal detachment occurred in 2 of 20 eyes and recurrence of the
      endophthalmitis in 1 of 20 eyes within the one year follow-up, 5 of 17 patients
      died. Enucleation was never necessary. CONCLUSION: Endogenous endophthalmitis is
      often misdiagnosed due to a severe underlying non-ophthalmological disease.
      Delayed presentation with consequent late initiation of therapy is an unresolved
      problem, because colleagues from other fields are often unexperienced in
      diagnosing the ocular infection. This is also a cause of the already poor visual
      prognosis. Ophthalmologists can usually only influence the choice of the proper
      therapy.

PMID- 29642264
TI  - [Possible Influencing Factors for the Prediction of Postoperative Visual Acuity
      Gain after Retroiridal Iris Claw Lens Implantation].
AB  - PURPOSE: To determine effect sizes for visual acuity (VA) and visual acuity gain
      (DeltaVA, pre- to postoperative) after the implantation of retroiridal Verisyse
      iris-claw lenses. MATERIALS AND METHODS: Nineteen eyes of 19 patients (mean age
      of 70 +/- 17 years) who underwent retoriridal iris claw lens implantation were
      included. Inclusion criteria were a lack of capsular support and complete data of
      pre- and postoperative corrected visual acuity, optical biometry, accompanying
      diseases and previous surgical intervention. A generalized linear model was
      established with postoperative visual acuity and visual acuity gain as dependent
      variables. Effect sizes were pseudoexfoliation syndrome, trauma, sex, previous
      surgical interventions as factors and axial length, average keratometry and
      corneal astigmatism as covariates. RESULTS: The mean visual acuity improved from
      0.72 +/- 0.65 logMAR preoperatively to 0.36 +/- 0.39 logMAR postoperatively
      (DeltaVA 0.36 +/- 0.69 logMAR). The average refractive IOL power was 19.4 +/- 4.9
      dpt. For modelling of VA/DeltaVA the axial length (p = 0.001)/axial length (p =
      0.001) and preop VA (p < 0.001) were tailored out as effect sizes. CONCLUSIONS:
      The axial length and preoperative VA affect postoperative visual acuity and
      visual acuity gain significantly. In eyes with lower preoperative visual acuity
      and in longer eyes larger visual acuity gain can be expected after retroiridal
      iris claw lens implantation.

PMID- 29642265
TI  - [Laser Trabeculoplasty in Modern Glaucoma Therapy - a Review].
AB  - BACKGROUND: Laser trabeculoplasty (LTP) is a well established treatment modality
      in the management of chronic open angle glaucoma. Nonetheless there is much
      variation in practice. METHODS: A literature search in the PubMed database was
      conducted and the most important evidence-based results were summarised. RESULTS:
      Argon laser trabeculoplasty (ALT) and selective laser trabeculoplasty (SLT) are
      safe and effective treatment modalities, achieving an IOP reduction of 20 - 30%.
      Similar success rates have been reported for both procedures. A 50% rate of
      failure occurs after 2 - 5 years. Repeat-ALT is associated with a lower IOP
      decrease and a shorter duration of treatment effect. Repetition of SLT after
      initial SLT seems to be associated with loss of efficiency as well. SLT has been
      shown to be successful after initial ALT, whereas there are no data on ALT after
      initial SLT. For advanced glaucoma on maximum medical therapy, low success rates
      have been reported with regard to additional interventions. CONCLUSION: LTP is a
      good option for initial and adjunctive treatment. In advanced glaucoma on maximum
      medical therapy, low target pressures are needed, and filtering surgery has to be
      considered.

PMID- 29642266
TI  - [The Assistant Doctors' Experience and Vocational Training Satisfaction in
      Ophthalmology in Bavaria: Outcomes of an Online Survey with Evaluation of the
      Vocational Training in Ophthalmic Surgery].
AB  - BACKGROUND: The following paper presents findings of an online survey on the
      assistant doctors' vocational training experiences and satisfaction in Bavaria
      with a special focus on the evaluation of their ophthalmic surgery training. The
      starting point for the survey were recent studies and experience reports on the
      situation of assistant doctors in ophthalmology, which have rudimentarily
      unveiled the assistant doctors' dissatisfaction with their ophthalmic surgery
      training as well as the neglect of support for acquiring ophthalmic surgery
      competences. METHOD: In March 2017, 219 assistant doctors in Bavaria were e
      mailed and asked to evaluate the quality of their experienced ophthalmic surgery
      training by completing an online questionnaire with a total of 38 open and closed
      questions. RESULTS: The findings of the survey have shown that 69% of the
      assistant doctors are dissatisfied with their ophthalmic surgery training. Over
      50% of the cases criticize the trainer doctor's loss of motivation to train their
      assistants in ophthalmic surgery. The following results create a fundamental
      tension to the assistant doctors' request for a substantiated training in that
      field, which over 90% of the respondents have articulated. Based on a defined
      catalogue of ophthalmic surgery interventions in the professional training
      guidelines for ophthalmologists in Bavaria, considerable deficits in the area of
      eyelid, tear duct and rectus eye muscle surgery could have been identified.
      CONCLUSION: Considering the limited scope and response rate, the survey presented
      in this paper must be defined as a pilot study. Nevertheless, the results plea
      for a nation-wide survey to be able to representatively formulate demand
      orientated approaches for improvement concerning the ophthalmic surgery training
      in Germany. However, it is clear that in comparison to conservative approaches in
      ophthalmology, the ophthalmic surgery training has been neglected to a certain
      point, although the professional training guidelines for ophthalmologists in
      Bavaria include a series of surgical interventions to be handled by assistant
      doctors.

PMID- 29642267
TI  - Quantile regression with nominated samples: An application to a bone mineral
      density study.
AB  - This paper studies quantile regression analysis with maxima or minima nomination
      sampling designs. These designs are often used to obtain more representative
      samples from the tails of the underlying distribution using the easy to access
      rank information during the sampling process. We propose new loss functions to
      incorporate the rank information of nominated samples in the estimation process.
      Also, we provide an alternative approach that translates estimation problems with
      nominated samples to corresponding problems under simple random sampling (SRS).
      Strategies are given to choose proper nomination sampling designs for a given
      population quantile. Numerical studies show that quantile regression models with
      maxima (or minima) nominated samples have higher relative efficiencies compared
      with their counterparts under SRS for analyzing the upper (or lower) tail
      quantiles of the distribution of the response variable. Results are then
      implemented on a large cohort study in the Canadian province of Manitoba to
      analyze quantiles of bone mineral density using available covariates. We show
      that in some cases, methods based on nomination sampling designs require about
      one-tenth of the sample used in SRS to estimate the lower or upper tail
      conditional quantiles with comparable mean squared errors. This is a dramatic
      reduction in time and cost compared with the usual SRS approach.

PMID- 29642268
TI  - Breaking the cycle of functional decline in older dialysis patients.
AB  - Currently, older adults comprise nearly one-third of prevalent US dialysis
      patients, and this proportion will increase as the population ages. Older
      dialysis patients experience greater morbidity and mortality than nondialysis
      patients of the same age, and in part, it is related to progressive functional
      decline. Progressive functional decline, characterized by need for assistance
      with more than 2 activities of daily living, contributes to risk of
      hospitalization, further functional decline, and subsequent nursing home
      placement when a patient no longer functions independently at home. Progressive
      functional decline may appear to be unavoidable for older dialysis patients;
      however, comprehensive geriatric assessment (CGA) may alleviate the prevalence
      and severity of functional decline. This editorial summarizes common risk factors
      of functional decline and introduces CGA as a potentially transformative approach
      to breaking the cycle of functional decline in older dialysis patients.

PMID- 29642269
TI  - Genome-wide detection of CNVs associated with beak deformity in chickens using
      high-density 600K SNP arrays.
AB  - Beak deformity (crossed beaks) is found in several indigenous chicken breeds
      including Beijing-You studied here. Birds with deformed beaks have reduced feed
      intake and poor production performance. Recently, copy number variation (CNV) has
      been examined in many species and is recognized as a source of genetic variation,
      especially for disease phenotypes. In this study, to unravel the genetic
      mechanisms underlying beak deformity, we performed genome-wide CNV detection
      using Affymetrix chicken high-density 600K data on 48 deformed-beak and 48 normal
      birds using penncnv. As a result, two and eight CNV regions (CNVRs) covering 0.32
      and 2.45 Mb respectively on autosomes were identified in deformed-beak and normal
      birds respectively. Further RT-qPCR studies validated nine of the 10 CNVRs. The
      ratios of six CNVRs were significantly different between deformed-beak and normal
      birds (P < 0.01). Within these six regions, three and 21 known genes were
      identified in deformed-beak and normal birds respectively. Bioinformatics
      analysis showed that these genes were enriched in six GO terms and one KEGG
      pathway. Five candidate genes in the CNVRs were further validated using RT-qPCR.
      The expression of LRIG2 (leucine rich repeats and immunoglobulin like domains 2)
      was lower in birds with deformed beaks (P < 0.01). Therefore, the LRIG2 gene
      could be considered a key factor in view of its known functions and its potential
      roles in beak deformity. Overall, our results will be helpful for future
      investigations of the genomic structural variations underlying beak deformity in
      chickens.

PMID- 29642270
TI  - Meaning, lived experience, empathy and boredom: Max van Manen on phenomenology
      and Heidegger.
AB  - Phenomenology as Qualitative Research: A Critical Analysis of Meaning Attribution
      has attracted the attention of Max van Manen, who has published a highly critical
      review article. Anyone reading this article, but unfamiliar with the book, will
      get a distorted view of what it is about, whom it is addressed to, what it tries
      to achieve, and how it goes about presenting its arguments. Not mildly distorted,
      in need of the odd correction here and there, but systematically misrepresented.
      One problem is that van Manen appears to have an idee fixe which prevents him
      from recognizing that the book is not about a certain philosophical tradition
      (known as "phenomenology"), but about a particular type of qualitative research
      (also known, unfortunately and confusingly, as "phenomenology"). A second idee
      fixe disposes him to misread an earlier article of mine and (much more seriously)
      three works by Heidegger. My aim in this article is to describe these two idees
      fixes, and exhibit their consequences. In doing so, I will examine what van Manen
      has to say on four crucial topics: meaning, lived experience, empathy, and
      Heidegger's analysis of boredom in The Fundamental Concepts of Metaphysics.

PMID- 29642272
TI  - "You don't look for it"-A study of Swiss professionals' awareness of young carers
      and their support needs.
AB  - While political and public interest in providing support for family carers is
      growing, so called young carers and young adult carers-young persons under the
      ages of 18 and 25 respectively-mostly remain unrecognised. Yet, this vulnerable
      group is in need of special attention and support from professionals in order to
      get along with the situation of an ill family member and the caring duties they
      perform. This paper presents the results from a focus group study on the level of
      awareness among professionals from healthcare, education and social services
      concerning the topic of caring children, adolescents and young adults; and on the
      practice tools they consider necessary and helpful in order to support young
      carers and young adult carers. Twenty-seven professionals from the German- and
      French-speaking parts of Switzerland participated in five focus groups. The focus
      groups were recorded and transcribed verbatim, and the transcripts were analysed
      using qualitative content analysis. Our findings show that the professionals have
      a low level of awareness of the issue of young carers and young adult carers and
      also highlight the professionals' willingness to engage with the subject. The
      results also show that professionals consider that practice tools (such as
      standardised questionnaires and check lists) could be important devices in
      providing support for young carers and young adult carers. These tools could be
      helpful in identifying this group, enabling them to identify themselves as such,
      and would ensure that they received appropriate support.

PMID- 29642271
TI  - The expression change of RORgammat, BATF, and IL-17 in Chinese vitiligo patients
      with 308 nanometers excimer laser treatment.
AB  - This study aims to explore the expression of RORgammat, BATF, and IL-17 in
      Chinese vitiligo patients with 308 nm excimer laser treatment. One hundred and
      sixty-four vitiligo patients treated with 308 nm excimer laser were enrolled as
      Case group and 137 health examiners as Control group. Quantitative real-time
      polymerase chain reaction and immunohistochemistry were conducted to detect the
      expressions of RORgammat, BATF, and IL-17. Expression of RORgammat, BATF, IL-17A,
      and IL-17F were higher in Case group than Control group, with the diagnostic
      accuracy of 88.04, 87.38, 97.34, and 89.04%, respectively. Pearson correlation
      analysis showed a positive correlation in RORgammat, BATF, IL-17A, and IL-17F
      mRNAs in vitiligo patients. Moreover, their expressions were higher in active
      vitiligo patients than stable ones. Besides, the expressions of RORgammat, BATF,
      IL-17A, and IL-17F in vitiligo skin were significantly higher than those in non
      lesional skin and normal controls. After treatment, their expressions were
      significantly decreased. Active vitiligo and the high expressions of RORgammat,
      BATF, and IL-17F were the independent risk factors for the ineffectiveness of 308
      nm excimer laser treatment. The expressions of RORgammat, BATF, IL-17 were
      significantly enhanced in vitiligo patients, which were correlated with the
      activity of vitiligo and 308 nm excimer laser therapeutic effects.

PMID- 29642273
TI  - The associations for separated parents in Italy: Their role for parents' well
      being and coparenting.
AB  - After separation or divorce, people generally experience a deterioration of
      health, not only in terms of physical well-being but also in terms of emotional
      and social well-being. In addition, when separated, individuals are parents as
      well and they are concerned with the well-being of their children. The main task
      for separated parents is to maintain a parental alliance (coparenting) for the
      sake of their children's well-being. Social support is a critical resource, which
      helps parents face their new life condition, promoting their psychological well
      being. In recent years in Italy, many associations targeting separated and
      divorced parents have been founded: They support ex-partners during and after
      separation and are active in defending their rights. These associations are
      voluntary associations/non-profit organisations and self-help groups, which are
      constituted by parents themselves who associate to support each other in the
      tasks connected with separation. The present study investigated, with an
      explorative aim, the role of these associations for separated parents' well-being
      and coparenting abilities. In particular, drawing on a sample of 318 Italian
      separated parents (73.30% fathers; 26.70% mothers) belonging to a formal
      association targeting separated parents, the study analysed whether and how the
      perception of being supported by the association was related to psychological and
      relational well-being and to coparenting. Results showed that the more parents
      perceived to be supported by the association the less they were depressed, the
      more they were satisfied with the relationship with children and friends, and the
      more they displayed coparenting abilities. Our findings suggest that social
      support from these associations is a resource for separated parents' health.

PMID- 29642274
TI  - Sample size evaluation for a multiply matched case-control study using the score
      test from a conditional logistic (discrete Cox PH) regression model.

PMID- 29642275
TI  - Development and validation of a new cognitive screening test: The Hong Kong Brief
      Cognitive Test (HKBC).
AB  - OBJECTIVES: To develop and examine the validity of a new brief cognitive test
      with less educational bias for screening cognitive impairment. METHODS: A new
      cognitive test, Hong Kong Brief Cognitive Test (HKBC), was developed based on
      review of the literature, as well as the views of an expert panel. Three groups
      of subjects aged 65 or above were recruited after written consent: normal older
      people recruited in elderly centres, people with mild NCD (neurocognitive
      disorder), and people with major NCD. The brief cognitive test, Mini-Mental State
      Examination (MMSE) and Montreal Cognitive Assessment Scale (MoCA), were
      administered to the subjects. The performance of HKBC in differentiating subjects
      with major NCD, mild NCD, and normal older people were compared with the clinical
      diagnosis, as well as the MMSE and MoCA scores. RESULTS: In total, 359 subjects
      were recruited, with 99 normal controls, 132 subjects with major NCD, and 128
      with mild NCD. The mean MMSE, MoCA, and HKBC scores showed significant
      differences among the 3 groups of subjects. In the receiving operating
      characteristic curve analysis of the HKBC in differentiating normal subjects from
      those with cognitive impairment (mild NCD + major NCD), the area under the curve
      was 0.955 with an optimal cut-off score of 21/22. The performances of MMSE and
      MoCA in differentiating normal from cognitively impaired subjects are slightly
      inferior to the HKBC. CONCLUSIONS: The HKBC is a brief instrument useful for
      screening cognitive impairment in older adults and is also useful in populations
      with low educational level.

PMID- 29642276
TI  - Phenomenology and qualitative research: Amedeo Giorgi's hermetic epistemology.
AB  - Amedeo Giorgi has published a review article devoted to Phenomenology as
      Qualitative Research: A Critical Analysis of Meaning Attribution. However, anyone
      reading this article, but unfamiliar with the book, will get a distorted view of
      what it is about, whom it is addressed to, what it seeks to achieve and how it
      goes about presenting its arguments. Not mildly distorted, in need of the odd
      correction here and there, but systematically misrepresented. The article is a
      study in misreading. Giorgi misreads the book's mise en scene; he misreads its
      narrative arc; he misreads individual arguments; he misreads short, simple
      passages; he misreads the philosophy of the science literature; he misreads his
      own data; he misreads the title; he misreads the blurb; he misreads the
      acknowledgements. In addition, there are serious failures of scholarship
      (ironically, he demonstrates how unacquainted he is with the relevant literature
      at the very moment he is accusing me of being ill-informed). In this reply, I
      provide several examples of these errors, but my primary aim is to understand why
      Giorgi's misreading is as ubiquitous as it is. To this end, I explain his
      mistakes by reference to the hermetic epistemology within which he is confined.

PMID- 29642277
TI  - A consensus statement on how to conduct inclusive health research.
AB  - BACKGROUND: The active involvement of people with intellectual disabilities in
      research, or inclusive research, is relatively common. However, inclusive health
      research is less common, even though it is expected to lead to appropriate
      healthcare and increased quality of life. Inclusive health research can build
      upon lessons learned from inclusive research. METHOD: A total of 17 experts on
      inclusive (health) research without intellectual disabilities and 40 experts with
      intellectual disabilities collaborated in this consensus statement. The consensus
      statement was developed in three consecutive rounds: (1) an initial feedback
      round; (2) a roundtable discussion at the 2016 International Association for the
      Scientific Study of Intellectual and Developmental Disabilities World Congress;
      and (3) a final feedback round. RESULTS: This consensus statement provides
      researchers with guidelines, agreed upon by experts in the field, regarding
      attributes, potential outcomes, reporting and publishing, and future research
      directions, for designing and conducting inclusive health research. CONCLUSIONS:
      Consensus was reached on how to design and conduct inclusive health research.
      However, this statement should be continuously adapted to incorporate recent
      knowledge. The focus of this consensus statement is largely on inclusive health
      research, but the principles can also be applied to other areas.

PMID- 29642278
TI  - Understanding the space of nursing practice in Colombia: A critical reflection on
      the effects of health system reform.
AB  - Worldwide, healthcare has been touched by neoliberal policies to the extent that
      it has some of its characteristics, such as being asymmetrical, competitive,
      dehumanized, and profit driven. In Colombia, Law 100/93 was created as an
      ambitious reform aimed at integrating the social security and public sectors of
      healthcare in order to create universal access, and at the same time to generate
      market competence with the objective of improving effectiveness and
      responsiveness. Instead, however, Colombian health reform has served to generate
      competition which has aggravated inequalities among people. Within this context,
      we practice nursing. As nurses, our responsibility is to advocate for our
      patients. We cannot ignore what is happening worldwide in hospitals and community
      health settings because our responsibility is to promote health, prevent disease,
      and care for human beings. So, today, when the world pushes for economical profit
      and competence on one hand, and, on the other, for moral compromises to care,
      respect, and advocacy for all human beings, being a nurse in the Colombian health
      system represents a challenge for us. This challenge is especially significant
      because harm and benefit, justice and injustice, respect and disrespect are
      separated by a fine line that is easy to transgress.

PMID- 29642279
TI  - Efficacy and tolerability of a lotion containing triethyl citrate, ethyl
      linoleate, and GT peptide-10 in the adjuvant treatment of hidradenitis
      suppurativa: Real-life data.
AB  - Hidradenitis suppurativa (HS) is a chronic disorder of terminal follicular
      epithelium in the apocrine gland-bearing areas. The long term therapy is based
      mainly on topical and/or systemic antibiotic use that could result in antibiotic
      resistance. The aim of our study was to present the real-life experience based on
      the efficacy and tolerability of a novel lotion containing triethyl-citrate,
      ethyl-linoleate, and g-peptide-10 in the treatment of mild to moderate HS that
      has already shown effectiveness in acne treatment. This was an open-label study
      on 30 patients of both sexes affected by HS. Patients were divided into two
      groups: 15 with Hurley I and 15 with Hurley II-III. The subjects were treated
      with the topical lotion, three-times-daily for eight weeks, with control at 4 (T1
      ) and eight weeks (T2 ). Any other concomitant treatment (both topical and/or
      systemic) was avoided during study period. Improvement was observed in both
      Sartorius score grading system and inflammatory and noninflammatory lesion
      counts. The novel lotion has proved to be effective and well-tolerated topical
      agent alone or in association with other topical and/or systemic tratments in HS,
      without side effects.

PMID- 29642280
TI  - A feasibility study on using tablet personal computers for self-reported symptom
      assessment in newly diagnosed lung cancer patients.
AB  - AIM: The study aimed to assess the feasibility and acceptability of an innovative
      tablet-assisted self-reported symptom assessment among newly diagnosed lung
      cancer patients. BACKGROUND: Routine symptom assessment for lung cancer patients
      in a fast-paced clinical environment is demanding. Mobile health technology
      offers a potential platform for symptom assessment and paves the way for tailored
      self-care intervention. DESIGN: A feasibility study using a mixed method design.
      METHOD: A convenience sample of 10 newly diagnosed lung cancer patients used
      tablet personal computers to self-report common symptoms: dyspnoea, fatigue,
      pain, and anxiety. A nurse reviewed the assessment results and provided tailored
      educational interventions. Acceptability was evaluated by the Electronic Self
      Report Assessment-Cancer. Semi-structured interviews were conducted to explore
      the patients' perceptions of this symptom assessment method. Data were collected
      from January to March 2016. RESULTS: An Electronic Self-Report Assessment-Cancer
      mean score of 23.5 (SD 2.7) showed moderate acceptance of the assessment method.
      Participants found this approach user-friendly and helpful in identifying their
      symptoms and they gained awareness and better understanding of them. CONCLUSION:
      Tablet-assisted symptom assessment is a feasible method that can be further
      tested in busy clinical settings to assess symptom burden and identify individual
      needs for tailoring symptom management plans.

PMID- 29642281
TI  - Fas Ligand localizes to intraluminal vesicles within NK cell cytolytic granules
      and is enriched at the immune synapse.
AB  - INTRODUCTION: T cell and NK cell cytotoxicity can be mediated via the
      perforin/granzyme system and Fas Ligand (FasL, CD178). FasL is synthesized as a
      type II transmembrane protein that binds its cognate receptor Fas (CD95).
      Membrane-bound FasL is expressed on the plasma membrane of activated lymphocytes
      and is the main form of FasL with cytotoxic activity, but whether FasL is
      delivered to the immune synapse along with granzyme and perforin-containing
      granules is unclear. METHODS: We stably expressed FasL-fluorescent fusion
      proteins into human NK cells and examined the localization of FasL relative to
      other intracellular markers by confocal and immunoelectron microscopy, and
      examined the trafficking of FasL during formation of immune synapses with HLA
      deficient B cells. RESULTS: FasL co-localized with CD63 more strongly than
      perforin or Lamp1+ in cytolytic granules. Electron microscopy revealed that FasL
      is enriched on intraluminal vesicles (ILVs) adjacent to the dense-core within
      cytolytic granules. In NK cells forming immune synapses with HLA-deficient B
      cells, a portion of FasL-containing granules re-localize toward the immune
      synapse, while a distinct pool of FasL remains at the distal pole of the cell.
      CONCLUSIONS: Localization of FasL to intra-luminal vesicles within cytolytic
      granules facilitates FasL trafficking to immune synapses and cytotoxic function
      in NK cells.

PMID- 29642282
TI  - Effect of the S-nitrosoglutathione reductase inhibitor N6022 on bronchial
      hyperreactivity in asthma.
AB  - RATIONALE: Patients with asthma demonstrate depletion of the endogenous
      bronchodilator GSNO and upregulation of GSNOR. OBJECTIVES: An exploratory proof
      of concept clinical study of N6022 in mild asthma to determine the potential
      bronchoprotective effects of GSNOR inhibition. Mechanistic studies aimed to
      provide translational evidence of effect. METHODS: Fourteen mild asthma patients
      were treated with intravenous N6022 (5 mg) or placebo and observed for 7 days,
      with repeated assessments of the provocative dose of methacholine causing a 20%
      fall in FEV1 (methacholine PC20 FEV1), followed by a washout period and crossover
      treatment and observation. In vitro studies in isolated eosinophils investigated
      the effect of GSNO and N6022 on apoptosis. MEASUREMENTS AND MAIN RESULTS: This
      was a negative trial as it failed to reach its primary endpoint, which was change
      from baseline in methacholine PC20 FEV1 at 24 h. However, our exploratory
      analysis demonstrated significantly more two dose-doubling increases in PC20 FEV1
      for N6022 compared with placebo (21% vs 6%, P < 0.05) over the 7-day observation
      period. Furthermore, a significant treatment effect was observed in the change in
      PC20 FEV1 from baseline averaged over the 7-day observation period (mean change:
      +0.82 mg/ml [N6022] from 1.34 mg/ml [baseline] vs -0.18 mg/ml [placebo] from 1.16
      mg/ml [baseline], P = 0.023). N6022 was well tolerated in mild asthmatics. In
      vitro studies demonstrated enhanced eosinophilic apoptosis with N6022.
      CONCLUSIONS: In this early phase exploratory proof of concept trial in asthma,
      N6022 did not significantly alter methacholine PC20 FEV1 at 24 h, but did have a
      treatment effect at 7 days compared to baseline. Further investigation of the
      efficacy of S-nitrosoglutathione reductase inhibition in a patient population
      with eosinophilic asthma is warranted.

PMID- 29642283
TI  - Hyperglycaemia is inversely correlated with live M. bovis BCG-specific CD4+ T
      cell responses in Tanzanian adults with latent or active tuberculosis.
AB  - INTRODUCTION: The rising prevalence of Diabetes mellitus (DM) in high TB-endemic
      countries may adversely affect sustainability of TB control since DM constitutes
      a risk factor for development of active tuberculosis (TB). The impact of DM on TB
      specific adaptive immune responses remains poorly addressed, particularly in
      people living in Sub-Saharan countries. We performed a functional
      characterization of TB specific cellular immune response in Tanzanian subjects
      with active or latent Mycobacterium tuberculosis (Mtb) infection stratified by
      their diabetic status. METHODS: HIV negative active TB patients (>=18 years) with
      Xpert MTB/RIF positive pulmonary TB were included before starting TB treatment in
      Dar es Salaam, Tanzania between April and December 2013. HIV negative healthy
      controls latently infected with TB but without past TB history were also
      included. Active and latent TB patients were stratified in two groups according
      to their diabetic status. Peripheral Blood Mononuclear cells were stimulated with
      either live M. bovis BCG or Mtb-specific peptide pools and analyzed by
      intracellular cytokine staining and polychromatic flow cytometry. RESULTS: Our
      results show a lower frequency of IFN-gamma CD4+ T cells in patients with active
      TB and DM compared to patients with active TB only after live M. bovis BCG (p =
      0.04) but not after Mtb peptide pools re-stimulation. Irrespective of TB status,
      level of glycaemia is selectively inversely correlated with IFN-gamma and TNF
      alpha CD4+ T cell production (p = 0.02 and p = 0.03) after live M. bovis BCG
      stimulation. CONCLUSIONS: These results support the hypothesis that
      hyperglycaemia negatively impacts antigen processing and/or presentation of whole
      mycobacteria delaying secretion of key cytokines involved in TB immunity.

PMID- 29642284
TI  - Scarless Genomic Point Mutation to Construct a Bacillus subtilis Strain
      Displaying Increased Antibiotic Plipastatin Production.
AB  - Bacillus strains produce various types of antibiotics, and random mutagenesis has
      traditionally been used to overproduce these natural metabolites. However, this
      method leads to the accumulation of unwanted mutations in the genome. Here, we
      rationally designed a single nucleotide substitution in the degU gene to generate
      a B. subtilis strain displaying increased plipastatin production in a foreign DNA
      free manner. The mutant strain (BS1028u) showed improved antifungal activity
      against Pythium ultimum. Notably, pps operon deletion in BS1028u resulted in
      complete loss of antifungal activity, suggesting that the antifungal activity
      strongly depends on the expression of the pps operon. Quantitative real-time PCR
      and lacZ assays showed that the point mutation resulted in 2-fold increased pps
      operon expression, which caused the increase in antifungal activity. Likewise,
      commercial Bacillus strains can be improved to display higher antifungal activity
      by rationally designed simple modifications of their genome, rendering them more
      efficient biocontrol agents.

PMID- 29642285
TI  - Probiotic Potential of Enterococcus faecium Isolated from Chicken Cecum with
      Immunomodulating Activity and Promoting Longevity in Caenorhabditis elegans.
AB  - Probiotics, including Enterococcus faecium, confer a health benefit on the host.
      An Enterococcus strain was isolated from healthy chicken cecum, identified as E.
      faecium by 16S rDNA gene sequence analysis, and designated as E. faecium L11. To
      evaluate the potential of E. faecium L11 as a probiotic, the gastrointestinal
      tolerance, immunomodulatory activity, and lifespan extension properties of the
      strain were assayed. E. faecium L11 showed >66% and >62% survival in artificial
      gastric juice (0.3% pepsin, pH 2.5) and simulated small intestinal juice (0.5%
      bile salt and 0.1% pancreatin), respectively. Heat-killed E. faecium L11
      significantly (p < 0.05) increased immune cell proliferation compared with
      controls, and stimulated the production of cytokines (IL-6 and TNF-alpha) by
      activated macrophages obtained from ICR mice. In addition, E. faecium L11 showed
      a protective effect against Salmonella Typhimurium infection in Caenorhabditis
      elegans. In addition, feeding E. faecium L11 significantly (p < 0.05) extended
      the lifespan of C. elegans compared with the control. Furthermore, genes related
      to aging and host defense were upregulated in E. faecium L11-fed worms. In
      conclusion, E. faecium L11, which prolongs the lifespan of C. elegans, may be a
      potent probiotic supplement for livestock.

PMID- 29642286
TI  - Functional Characterization of the C-Terminus of YhaV in the Escherichia coli
      PrlF-YhaV Toxin-Antitoxin System.
AB  - Bacterial programmed cell death is regulated by the toxin-antitoxin (TA) system.
      YhaV (toxin) and Pr1F (antitoxin) have been recently identified as a type II TA
      system in Escherichia coli. YhaV homologs have conserved active residues within
      the C-terminus, and to characterize the function of this region, we purified
      native YhaV protein (without denaturing) and constructed YhaV proteins of varying
      lengths. Here, we report a new low-temperature method of purifying native YhaV,
      which is notable given the existing challenges of purifying this highly toxic
      protein. The secondary structures and thermostability of the purified native
      protein were characterized and no significant structural destruction was
      observed, suggesting that the observed inhibition of cell growth in vivo was not
      the result of structural protein damage. However, it has been reported that
      excessive levels of protein expression may result in protein misfolding and
      changes in cell growth and mRNA stability. To exclude this possibility, we used
      an [35S]-methionine prokaryotic cell-free protein synthesis system in vitro in
      the presence of purified YhaV, and two C-terminal truncated forms of this protein
      (YhaV-L and YhaV-S). Our results suggest that the YhaV C-terminal region is
      essential for mRNA interferase activity, and the W143 or H154 residues may play
      an analogous role to Y87 of RelE.

PMID- 29642287
TI  - Saci_1816: A Trehalase that Catalyzes Trehalose Degradation in the
      Thermoacidophilic Crenarchaeon Sulfolobus acidocaldarius.
AB  - Previously, a cytosolic trehalase (TreH) from the hyperthermophilic archaeon
      Sulfolobus acidocaldarius was reported; however, the gene responsible for the
      trehalase activity was not identified. Two genes, saci_1816 and saci_1250, that
      encode the glycoside hydrolase family 15 type glucoamylase-like proteins in S.
      acidocaldarius were targeted and expressed in Escherichia coli, and their
      abilities to hydrolyze trehalose were examined. Recombinant Saci_1816 hydrolyzed
      trehalose exclusively without any help from a cofactor. The mass spectrometric
      analysis of partially purified native TreH also confirmed that Saci_1816 was
      involved in proteins exhibiting trehalase activity. Optimal trehalose hydrolysis
      activity of the recombinant Saci_1816 was observed at pH 4.0 and 60 degrees C.
      The pH dependence of the recombinant enzyme was similar to that of the native
      enzyme, but its optimal temperature was 20-25 degrees C lower, and its
      thermostability was also slightly reduced. From the biochemical and structural
      results, Saci_1816 was identified as a trehalase responsible for trehalose
      degradation in S. acidocaldarius. Identification of the treH gene confirms that
      the degradation of trehalose in Sulfolobus species occurs via the TreH pathway.

PMID- 29642288
TI  - Generation of a High-Growth Influenza Vaccine Strain in MDCK Cells for Vaccine
      Preparedness.
AB  - As shown during the 2009 pandemic H1N1 (A(H1N1)pdm09) outbreak, egg-based
      influenza vaccine production technology is insufficient to meet global demands
      during an influenza pandemic. Therefore, there is a need to adapt cell culture
      derived vaccine technology using suspended cell lines for more rapid and larger
      scale vaccine production. In this study, we attempted to generate a high-growth
      influenza vaccine strain in MDCK cells using an A/Puerto/8/1934 (H1N1) vaccine
      seed strain. Following 48 serial passages with four rounds of virus plaque
      purification in MDCK cells, we were able to select several MDCK-adapted plaques
      that could grow over 108 PFU/ml. Genetic characterization revealed that these
      viruses mainly had amino acid substitutions in internal genes and exhibited
      higher polymerase activities. By using a series of Rg viruses, we demonstrated
      the essential residues of each gene and identified a set of high-growth strains
      in MDCK cells (PB1D153N, M1A137T, and NS1N176S). In addition, we confirmed that
      in the context of the high-growth A/PR/8/34 backbone, A/California/7/2009 (H1N1),
      A/Perth/16/2009 (H3N2), and A/environment/Korea/deltaW150/2006 (H5N1) also showed
      significantly enhanced growth properties (more than 107 PFU/ml) in both attached-
      and suspended-MDCK cells compared with each representative virus and the original
      PR8 vaccine strain. Taken together, this study demonstrates the feasibility of a
      cell culture-derived approach to produce seed viruses for influenza vaccines that
      are cheap and can be grown promptly and vigorously as a substitute for egg-based
      vaccines. Thus, our results suggest that MDCK cell-based vaccine production is a
      feasible option for producing large-scale vaccines in case of pandemic outbreaks.

PMID- 29642289
TI  - Fractionated Coptis chinensis Extract and Its Bioactive Component Suppress
      Propionibacterium acnes-Stimulated Inflammation in Human Keratinocytes.
AB  - Coptis chinensis (CC) is widely used in Asian countries to treat inflammatory
      diseases. We investigated the anti-inflammatory activity of the aqueous fraction
      separated from CC extract and of berberine, its key bioactive component, in human
      keratinocytes and the possible molecular mechanisms underlying this. Treating
      HaCaT keratinocytic cells with heat-killed Propionibacterium acnes induced nitric
      oxide and proinflammatory cytokine (e.g., tumor necrosis factor-alpha,
      interleukin (IL)-1beta, and IL-8) production and their mRNA expression; these
      effects were suppressed by pretreatment with the aqueous fraction or berberine,
      which also suppressed the phosphorylation of ERK, JNK, and p38 kinases and the
      nuclear expression of nuclear factor (NF)-kappaB p65 in P. acnes-stimulated
      cells. Thus, the aqueous fraction and berberine effectively exerted anti
      inflammatory activities by suppressing mitogen-activated protein kinase and NF
      kappaB signaling pathways in human keratinocytes and may be used for treating P.
      acnes-induced inflammatory skin diseases.

PMID- 29642290
TI  - Nematicidal and Plant Growth-Promoting Activity of Enterobacter asburiae HK169:
      Genome Analysis Provides Insight into Its Biological Activities.
AB  - In the course of screening for microbes with nematicidal activity, we found that
      Enterobacter asburiae HK169 displayed promising nematicidal activity against the
      root-knot nematode Meloidogyne incognita, along with plant growth-promoting
      properties. Soil drenching of a culture of HK169 reduced gall formation by 66%
      while also increasing root and shoot weights by 251% and 160%, respectively,
      compared with an untreated control. The cell-free culture filtrate of the HK169
      culture killed all juveniles of M. incognita within 48 h. In addition, the
      nematicidal activity of the culture filtrate was dramatically reduced by a
      protease inhibitor, suggesting that proteolytic enzymes contribute to the
      nematicidal activity of HK169. In order to obtain genomic information about the
      HK169 isolate related to its nematicidal and plant growth-promoting activities,
      we sequenced and analyzed the whole genome of the HK169 isolate, and the
      resulting information provided evidence that the HK169 isolate has nematicidal
      and plant growth-promoting activities. Taken together, these observations enable
      the future application of E. asburiae HK169 as a biocontrol agent for nematode
      control and promote our understanding of the beneficial interactions between E.
      asburiae HK169 and plants.

PMID- 29642291
TI  - Statistical Optimization of Medium Components by Response Surface Methodology to
      Enhance Menaquinone-7 (Vitamin K2) Production by Bacillus subtilis.
AB  - Optimization of the culture medium to maximize menaquinone-7 (MK-7) production by
      Bacillus subtilis strain KCTC 12392BP in static culture was carried out using
      statistical experimental methods, including one factor at a time, fractional
      factorial design, and response surface methodology (RSM). Maltose (carbon
      source), tryptone (nitrogen source), and glycerol (activator) were identified as
      the key medium components for MK-7 synthesis by the fractional factorial design,
      and were selected for statistical optimization by RSM. The statistical analysis
      indicated that, in the range that was studied, maltose, tryptone, and glycerol
      were all critical factors having profound effects on the production of MK-7, with
      their coefficients for linear and quadratic all significant at the p < 0.05
      level. The established model was efficient and feasible, with a determination
      coefficient (R2) of 0.9419. The predicted concentrations of maltose, tryptone,
      and glycerol in the optimal medium were determined as 36.78, 62.76, and 58.90
      g/l, respectively. In this optimized medium, the maximum yield of MK-7 reached a
      remarkably high level of 71.95 +/- 1.00 MUg/ml after 9 days of static
      fermentation, which further verified the practicability of this optimized
      strategy.

PMID- 29642292
TI  - Improved Anti-Cancer Effect of Curcumin on Breast Cancer Cells by Increasing the
      Activity of Natural Killer Cells.
AB  - Curcumin is known to possess various biological functions, including anti
      inflammatory, antioxidative, and anti-cancer activities. Natural killer (NK)
      cells are large lymphocytes that directly kill cancer cells. However, many
      aggressive cancers, including breast cancer, were reported to escape the
      successful killing of NK cells in a tumor microenvironment. In this study, we
      investigated the anti-cancer effect of curcumin in coculture of human breast
      carcinoma MDA-MB-231 and NK (NK-92) cells. We found that curcumin had an immune
      stimulatory effect on NK-92 by increasing the surface expression of the CD16+ and
      CD56dim population of NK-92. We confirmed that the cytotoxic effect of NK-92 on
      MDA-MB-231 was significantly enhanced in the presence of curcumin, which was
      highly associated with the activation of Stat4 and Stat5 proteins in NK-92.
      Finally, this improved anticancer effect of curcumin was correlated with
      decreased expression of pErk and PI3K in MDA-MB-231.

PMID- 29642293
TI  - Enzyme Hydrolysates of Ginseng Marc Polysaccharides Promote the Phagocytic
      Activity of Macrophages Via Activation of TLR2 and Mer Tyrosine Kinase.
AB  - Although ginseng marc is a by-product obtained during manufacturing of various
      commercial ginseng products and has been routinely discarded as a waste, it still
      contains considerable amounts of potential bioactive compounds, including
      saponins and polysaccharides. Previously, we reported that ginseng
      oligosaccharides derived from ginseng marc polysaccharides by enzymatic
      hydrolysis exert immunostimulatory activities in macrophages and these activated
      macrophages are in turn able to inhibit the growth of skin melanoma cells by
      inducing apoptosis. In the present study, a more detailed investigation of the
      immunostimulatory activity and underlying action mechanisms of an enzymatic
      hydrolysate (GEH) containing these oligosaccharides derived from ginseng marc
      polysaccharides was performed. The levels of proinflammatory cytokines and anti
      inflammatory cytokines were measured in GEH-stimulated RAW264.7 macrophages using
      RT-PCR analysis and ELISA. The expression levels of Toll-like receptor 2 (TLR2)
      and TLR4, Dectin-1, and MerTK were measured by RT-PCR analysis or western blot
      analysis, and the phagocytic activities of GEH-challenged bone marrow-derived
      macrophages toward apoptotic Jurkat cells were assayed using fluorescence
      microscopy. GEH induced the production of both proinflammatory cytokines TNF
      alpha and IL-6, and anti-inflammatory cytokine IL-10 in RAW 264.7 cells. The
      expression of the TLR2 and MerTK mRNAs was increased upon GEH treatment.
      Phagocytosis of apoptotic Jurkat cells was enhanced in GEH-treated macrophages.
      Based on the results, this enzymatic hydrolysate (GEH) containing
      oligosaccharides exerts immunostimulatory effects by maintaining the balance
      between M1 and M2 cytokines, facilitating macrophage activation and contributing
      to the efficient phagocytosis of apoptotic cells. Therefore, the GEH could be
      developed as value-added, health-beneficial food materials with immunostimulatory
      effects.

PMID- 29642294
TI  - Characterization of Three Extracellular beta-Glucosidases Produced by a Fungal
      Isolate Aspergillus sp. YDJ14 and Their Hydrolyzing Activity for a Flavone
      Glycoside.
AB  - A cellulolytic fungus, YDJ14, was isolated from compost and identified as an
      Aspergillus sp. strain. Three extracellular beta-glucosidases, BGL-A1, BGL-A2,
      and BGL-A3, were separated using ultrafiltration, ammonium sulfate fractionation,
      and High-Q chromatography. The molecular masses of the three enzymes were
      estimated to be 100, 45, and 40 kDa, respectively, by SDS-PAGE. The optimum pH
      and temperature of BGL-A3 were 5.0 and 50 degrees C, respectively, whereas the
      optimum pH and temperature of BGL-A1 and BGL-A2 were identical (4.0 and 60
      degrees C, respectively). The half-life of BGL-A3 at 70 degrees C (2.8 min) was
      shorter than that of BGL-A1 and BGL-A2 (12.1 and 8.8 min, respectively). All
      three enzymes preferred p-nitrophenyl-beta-D-glucopyranoside (pNPG) and hardly
      hydrolyzed cellobiose, suggesting that these enzymes were aryl beta-glucosidases.
      The Km of BGL-A3 (1.26 mM) for pNPG was much higher than that of BGL-A1 and BGL
      A2 (0.25 and 0.27 mM, respectively). These results suggested that BGL-A1 and BGL
      A2 were similar in their enzymatic properties, whereas BGL-A3 differed from the
      two enzymes. When tilianin (a flavone glycoside of acacetin) was reacted with the
      three enzymes, the inhibitory activity for monoamine oxidase, a target in the
      treatment of neurological disorders, was similar to that shown by acacetin. We
      conclude that these enzymes may be useful in the hydrolysis of flavone glycosides
      to improve their inhibitory activities.

PMID- 29642295
TI  - Development and Characterization of Monoclonal Antibodies against Nucleoprotein
      for Diagnosis of Influenza A Virus.
AB  - Influenza, which is a highly contagious disease caused by the influenza A virus,
      continues to be a major health concern worldwide. Although the accurate and early
      diagnosis of influenza virus infection is important for controlling the spread of
      this disease and rapidly initiating antiviral therapy, the current influenza
      diagnostic kits are limited by their low sensitivity. In this study, we developed
      several new influenza nucleoprotein (NP)-specific monoclonal antibodies (mAbs)
      and compared their sensitivity and specificity of those with commercially
      available anti-NP mAbs. Three mAbs, designated M24.11, M34.3, and M34.33,
      exhibited higher reactivities to recombinant NPs and A/Puerto Rico/8/1934 (H1N1)
      viral lysates compared with the commercial mAbs, as assessed using enzyme-linked
      immunosorbent assays. M34.3 and M34.33 showed higher reactivities with
      A/California/04/09 (pandemic H1N1) and A/Philippines/2/82 (H3N2) viral lysates
      than the commercial mAbs. In contrast, M24.11 had marked reactivity with H3N2 but
      not with pandemic H1N1. Immunofluorescent confocal microscopy showed that the
      three mAbs effectively detected the presence of influenza virus in lung tissues
      of mice infected with A/Puerto Rico/8/1934. These results indicate that the newly
      developed M34.3 and M34.33 mAbs could be useful for the development of influenza
      diagnostics.

PMID- 29642296
TI  - ENTEROAGGREGATIVE ESCHERICHIA COLI O104 FROM THAI AND IMPORTED MALAYSIAN RAW
      BEEF.
AB  - Local Thai and imported Malaysian beef in southern Thailand area carryseveral
      Shiga toxin-producing Escherichia coli (STEC) serotypes. STEC O104 is animportant
      pathogen capable of causing outbreaks with considerable morbidityand mortality.
      This study investigated the presence of E. coli O104 from local Thaiand imported
      Malaysian beef obtained from markets in Hat Yai City, SongkhlaProvince during
      August 2015 - February 2016. Thirty-one E. coli O104 strainswere isolated from 12
      beef samples (16% and 23% Thai and imported Malaysian,respectively). Thirty
      strains possessed aggA (coding for a major component ofAAF/I fimbriae), a gene
      associated with enteroaggregative E. coli (EAEC) pathotype,and all strains
      carried fimH (encoding Type 1 fimbriae). Thirty strainsbelonged to phylogenetic
      group B1 and one strain (from Malaysian beef) to groupA. Agglutination of yeast
      cells was observed among 29 E. coli O104 strains. Investigationof stx2 phage
      occupancy loci demonstrated that sbcB was occupied in 12strains. Antimicrobial
      susceptibility assay revealed that 7 strains were resistantto at least one
      antimicrobial agent and two were multi-drug resistant. One straincarried extended
      spectrum beta-lactamase gene blaCTX-M and three carried blaTEM. PFGE-generated
      DNA profiling showed identical DNA pattern between that ofone EAEC O104 strain
      from Thai beef and another from Malaysian beef, indicatingthat these two strains
      originated from the same clone. This is the first reportin Thailand describing
      the presence of EAEC O104 from both Thai and importedMalaysian beef and their
      transfer between both countries. Thorough surveillanceof this pathogen in fresh
      meats and vegetables should help to prevent any possibleoutbreak of E. coli O104.

PMID- 29642297
TI  - PREVALENCE AND ANTIBIOTIC SUSCEPTIBLITY OF METHICILLIN RESISTANT STAPHYLOCOCCUS
      AUREUS, COLLECTED AT THAMMASAT UNIVERSITY HOSPITAL, THAILAND, AUGUST 2012 - JULY
      2015.
AB  - We analyzed data of Staphylococcus aureus isolated from patients
      attendingThammasat University Hospital, Thailand from August 2012 to July 2015.
      Intotal, 232/502 (46%) S. aureus isolates were methicillin-resistant S. aureus
      (MRSA).There was a declining trend of proportion of MRSA infection, but the
      prevalenceof MRSA in the last year of study remained high (38%). All 32 MRSA
      infectedoutpatients had history of exposure to healthcare facilities during the
      previous twomonths and thus were not considered as having community-associated
      MRSA.In addition, all these strains were negative for pvl, suggesting that these
      strainswere hospital-associated MRSA. All MRSA stains were susceptible to
      linezolid,teicoplanin and vancomycin, but resistance to erythromycin and
      clindamycinwere nearly 100%. Fifty-two percent and 87% of MRSA strains were
      susceptibleto tetracycline and trimethoprim-sulfamethoxazole, respectively. These
      resultsemphasize the necessity of long-term surveillance and monitoring of
      antimicrobialsusceptibility pattern of MRSA.

PMID- 29642298
TI  - REPEATED SCLEROTHERAPY SUCCESSFULLY TREATS A CHILD WITH IDIOPATHIC CHYLURIA: A
      CASE REPORT.
AB  - We describe a clinical course of idiopathic chyluria in a previouslyhealthy 8
      year-old Thai boy, with a 1-year history of cloudy white urine
      undergoingantibiotic treatment. The patient was investigated for the causes but
      theyall proved negative. Cystoscopy and retrograde pyelography demonstrated
      arenolymphatic fistula of the right kidney. The patient was refractory to a
      mediumchaintriglyceride-rich diet. Ultimately, sclerotherapy with 1% povidone
      iodine wasemployed twice, which resulted in a resolution of the disorder. We
      emphasize thatchyluria, even though a very rare condition of chylous disorders,
      but ultimatelycan be initially managed by providing a medium-chain triglyceride
      rich diet andis curable by sclerotharapy. Importantly, medium-chain triglyceride
      rich diet canbe applied to treat other types of chylous disorders.

PMID- 29642299
TI  - PARTNER NOTIFICATION OUTCOMES AMONG MALE GONORRHEA PATIENTS AT BANGRAK HOSPITAL,
      BANGKOK, THAILAND.
AB  - Partner notification (PN) is an important strategy to control sexuallytransmitted
      infections. The objective of this study was to assess the outcomes ofPN in order
      to improve control of sexually transmitted infections. We retrospectivelyreviewed
      heterosexual male gonorrhea cases who presented for treatmentto Bangrak Hospital
      during 2008 to determine the percent PN, the percent ofsuccessful partner
      management (SPM) and the factors associated with both. Weused univariate and
      multivariate analyses to determine significant associationsbetween
      characteristics of index cases and PN outcomes. We reviewed the medicalrecords of
      418 index cases. The median age of the subjects reviewed was 30 yearsold (range:
      14-63). Six hundred ninety-two partners were identified. Of those,367 partners
      (53.0%) were notified by 311 index cases; 95 partners (25.9% of thenotifications)
      of the 89 index cases presented for treatment. The medical recordsof 92 partners
      were available to review: 61 (66%) had gonorrhea, chlamydia, orgenital herpes
      infections. The median period from being notified to seeking carewas 2.5 days
      (range: 0-92); 80% sought care within 9 days of notification. Spousesand
      girlfriends were the major partners being notified and had greater SPM.
      Onmultivariate analysis, a greater notification rate was found among index
      caseswho were government workers or had a steady relationship. A higher SPM
      ratewas associated with index cases who were aged >=25 years, married or had
      asteady relationship. The PN rate among the studied index cases was
      inadequate.Further studies are needed to develop successful methods to improve PN
      ratesand SPM rates in order to improve sexually transmitted infection control in
      thestudy population.

PMID- 29642300
TI  - NURSES' ATTITUDES TOWARDS CO-WORKERS INFECTED WITH HIV OR HEPATITIS B OR C IN
      VIETNAM.
AB  - Stigma and discrimination experienced by nurses infected with
      humanimmunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus
      (HCV)potentially undermine their positions. The aim of this study was to
      determine thefactors associated with nurses' attitudes towards accepting co
      workers with HIV,HBV, or HCV. The study design was descriptive and cross
      sectional. Four hundredVietnamese nurses participated in this study using
      stratified random sampling attwo public hospitals in Hanoi, Vietnam. A self
      administrated questionnaire wasused to obtain data. Descriptive statistics and
      multivariable logistic regression wasperformed to analyze data. Nine percent of
      nurses had experienced a needle-stickor sharps injury (NSI) from a patient
      infected with HIV, and 15.8% of respondentsreported having a previous NSI from a
      patient infected with HBV or HCV. Somenurses reported that they could not accept
      contact between patients and nursesinfected with HIV (25.2%) and HBV or HCV
      (12.7%). Older age and a belief thatcolleagues should disclose their infection
      status were associated with positiveattitudes towards HIV-, HBV-, or HCV-positive
      colleagues. Fear of transmissionwas associated with negative attitudes towards
      HIV-positive co-workers. Infectedemployees disclosure of their status may help
      their colleagues to be more acceptingby providing appropriate workplace
      adjustments for infected employees.HIV is generally a more stigmatized infection,
      and therefore attitudes towardsHIV-positive co-workers might be affected by fear
      of transmission. Providingeducation to recognize infectious risk may be effective
      in improving nurses' attitudesin Vietnam, as elsewhere.

PMID- 29642301
TI  - AWARENESS, KNOWLEDGE LEVEL, AND MISCONCEPTIONS ABOUT SEXUALLY TRANSMITTED
      INFECTIONS AMONG SECONDARY SCHOOLSTUDENTS IN BRUNEI DARUSSALAM.
AB  - Sexually transmitted infections (STI) remain an important publichealth issue
      globally, particularly among the young population. Despite beingpreventable and
      curable, STI continue to spread. Lack of access to treatment isan important
      factor in many developing and underdeveloped nations. Lack ofawareness and
      knowledge is another important factor. This study assessed theawareness,
      knowledge, and misconceptions among secondary school students onSTI. Overall,
      awareness was poor but better among male students and those inthe Pure Science
      academic streaming. Similarly, the knowledge level of STI wasalso poor: low level
      (63.0%), moderate level (34.4%), and high level (2.6%). Malestudents (p=0.014)
      and Pure Science academic streaming students (p<0.001) scoredbetter. There were
      misconceptions, but poor knowledge was predominant. Commonsources of information
      were teachers, health professionals, Internet, parentsand TV programs. Based on
      our study, more needs to be done to improve theawareness and knowledge level of
      STI, and detailed inclusion into the educationalcurriculum may be a
      consideration.

PMID- 29642302
TI  - HEALTH STATUS, ENVIRONMENTAL LIVING CONDITIONS AND MICROBIAL INDOOR AIR QUALITY
      AMONG MIGRANT WORKER HOUSEHOLDSIN THAILAND.
AB  - A large number of migrants have move to cities in Thailand seeking
      employment.These people may be at increased risk for environmental health
      problems.We studied the health status, environmental living conditions and
      microbial indoorair quality (IAQ) among selected groups of migrant workers and
      their households inMueang District, Samut Sakhon, central Thailand. We conducted
      a cross sectionalstudy of 240 migrant workers and their households randomly
      selected by multistagesampling. The person responsible for hygiene at each
      studied household wasinterviewed using a structured questionnaire. Two indoor air
      samples were takenfrom each household (480 indoor air samples) to determine
      bacterial and fungalcounts using a Millipore air tester; 240 outdoor air samples
      were collected for comparison.Ninety-nine point six percent of study subjects
      were Myanmar, 74.2% wereaged 21-40 years, 91.7% had a primary school level
      education or lower and 53.7%had stayed in Thailand less than 5 years. Eight point
      three percent had a historyof an underlying disease, 20.8% had a recent history
      of pulmonary tuberculosis ina family member within the previous year. Forty-three
      point eight percent had acurrent illness related to IAQ during a previous month.
      Twenty-one point threewere current cigarette smokers, 15.0% were current alcohol
      consumers, and 5.0%exercises >=3 times per week. Forty-nine point two percent
      never opened the windowsof their bedrooms or living rooms for ventilation, 45%
      never cleaned theirwindow screens, and 38.3% never put their pillows or
      mattresses in the sunlight. Themean(+/-SD) air bacterial count was 230(+/-229)
      CFU/m3 (outdoor air = 128+/-82 CFU/m3), and the mean fungal count was 630(+/-842)
      CFU/m3 (outdoor air = 138+/-94 CFU/m3). When the bacterial and fungal counts were
      compared with the guidelines of theAmerican Conference of Governmental Industrial
      Hygienists, the bacterial countsin 6.5% of houses surveyed and the fungal counts
      in 28.8% of house surveyed werehigher than the recommended levels (<500 CFU/m3).
      Bacterial and fungal counts inthe sample households were not significantly
      correlated with household hygienepractice scores (p>0.05). There was a positive
      correlation between bacterial countsand fungal counts in household air samples,
      r=0.28, p<0.001.

PMID- 29642303
TI  - CAPACITY BUILDING PROCESS IN ENVIRONMENTAL AND HEALTH IMPACT ASSESSMENT FOR A
      THAI COMMUNITY.
AB  - This research aimed at exploring the development of the capacitybuildingprocess
      in environmental and health impact assessment, including theconsideration of
      subsequent, capacity-building achievements. Data were gatheredthrough
      questionnaires, participatory observations, in-depth interviews, focusgroup
      discussions, and capacity building checklist forms. These data were analyzedusing
      content analysis, descriptive statistics, and inferential statistics. Our
      studyused the components of the final draft for capacity-building processes
      consistingof ten steps that were formulated by synthesis from each respective
      process. Additionally,the evaluation of capacity building levels was performed
      using 10-itemevaluation criteria for nine communities. The results indicated that
      the communitiesperformed well under these criteria. Finally, exploration of the
      factors influencingcapacity building in environmental and health impact
      assessment indicated thatthe learning of community members by knowledge exchange
      via activities andstudy visits were the most influential factors of the capacity
      building processes inenvironmental and health impact assessment. The final
      revised version of capacitybuildingprocess in environmental and health impact
      assessment could serve as abasis for the consideration of interventions in
      similar areas, so that they increasedcapacity in environmental and health impact
      assessments.

PMID- 29642304
TI  - ASSESSMENT OF A NEW SMOKING CESSATION PROGRAM AT THAMMASAT UNIVERSITY HOSPITAL,
      PATHUM THANI, THAILAND.
AB  - The Smoking Cessation Clinic (SCC) at Thammasat University Hospitalhad only 27
      patients from October 2013 to September 2014 and a quit rate of only3.7%. A new
      smoking cessation program was implemented at the end of 2014 toimprove success
      rates. This new program is an interdisciplinary program thatincludes several
      health care specialists. The study aimed to examine the characteristicsof the
      smokers and the outcomes after implementing the new programwith an
      interdisciplinary approach at the SCC in order to gain data to improvethe
      efficacy of the SCC. This prospective descriptive study was conducted by theSCC
      from December 2014 to December 2015. During the study period 111 patientsattended
      the SCC under the new program and all were included in the survey;100 (90.1%)
      were men. The mean (+/-SD) age of these patients was 56.5+/-13.5 years.The mean
      (+/-SD) age of onset of smoking was 18.5+/-5.5 years. Smoking cessationin the
      program was checked by measuring the exhaled carbon monoxide levels at6 months
      after reporting smoking cessation. A level less than 10 parts per millionwas
      considered not to be a smoker. Of the 111 patients, 14 (12.6%) had
      reportedsmoking cessation and had an exhaled carbon monoxide level less than 10
      parts permillion. The new smoking cessation program was attended by more patients
      andhad a higher success rate than the previous smoking cessation program,
      althoughthe smoking cessation success rate was still low. Further studies are
      needed todetermine which factors improved cessation rates and to determine other
      factorsassociated with successful smoking cessation in the study population.

PMID- 29642305
TI  - EXHALED CARBON MONOXIDE LEVELS AMONG TOBACCO SMOKERS BY AGE.
AB  - Measurement of exhaled carbon monoxide (ECO) has been used toconfirm self
      reported tobacco smoking. There is little data regarding ECO levelsamong Thai
      tobacco smokers by age. The objectives of this study were to determineECO cutoff
      level to confirm tobacco smoking and to assess whether the cutofflevel varies by
      age. During 2009 we evaluated 875 Thai volunteers aged 16-70years, residing in
      Pathum Thani (central Thailand) and Khon Kaen (northeasternThailand). Among the
      875 volunteers, there were 584 non-smokers and 291 smokers.Each subject was
      interviewed and had their ECO level measured. The meanECO level was 11.24 ppm
      among smokers and 2.25 ppm among non-smokers.The best ECO cutoff level to
      distinguish 291smokers from 584 non-smokers was5 ppm (sensitivity 79.0%,
      specificity 89.9%).The optimal ECO cutoff level variedby age-group. For subjects
      aged 16-25 years, the best ECO cutoff level was 4 ppm(sensitivity 85.2%,
      specificity 77.5%) and for subject aged 26-70 years, the best ECOcutoff level was
      5 ppm (sensitivity 79.4%, specificity 91.2%).These levels by ageshould be used
      among Thai subjects to determine smoking.

PMID- 29642306
TI  - A WEIGHT-LOSS PROGRAM FOR MEDICAL STUDENTS IN THAILAND: AN EVALUATION OF RELATED
      KNOWLEDGE, PREVAILING ATTITUDES, AND PROGRAM OUTCOMES FOR WEIGHT LOSS.
AB  - Millions of people, worldwide, struggle with being overweight or obese.Medical
      students, who will eventually become physicians, should be good rolemodels for
      patients; however, some medical students are themselves overweight orobese. The
      aim of this study was to evaluate the efficacy of a weight-loss programfor
      medical students in Thailand. A six-month weight reduction program wasdesigned
      consisted of three full-day sections that were scheduled, as follows: DayOne, End
      of Week One, and End of Week Eight. The interventions incorporatedvarious
      behavior modification strategies. Participant anthropometric measurementswere
      recorded. Obesity-related knowledge, perception, attitude, and
      inappropriateweight-loss behaviors were obtained by validated questionnaire. At
      theend of the study, statistically significant weight loss was demonstrated
      (median2.70 kg, p<0.05) compared to baseline. Moreover, participant knowledge
      significantlyincreased and inappropriate weight-loss behaviors significantly
      decreased(p<0.05 and p<0.05, respectively) compared to baseline. Given the
      demonstratedmodest effectiveness of this low-intensity weight reduction program,
      this interventionshould be considered as an effective education tool for medical
      students.

PMID- 29642307
TI  - IMPACT OF PERSONALITY TRAIT AND PROFESSIONAL IDENTITY ON WORK-RELATED DEPRESSION,
      ANXIETY AND IRRITATION AMONG CHINESE NURSES.
AB  - This study aimed to explore the impact of personality trait and
      professionalidentity on work-related depression, anxiety, irritation among
      Chinesenurses. Hospital nurses are known to work in stressful environment, which
      maylead to depression, anxiety and irritation symptoms. Few studies have been
      doneto address this problem from the perspective of personality trait and
      professionalidentity in Chinese nurses. This was a cross sectional study. Data
      were collectedfrom twenty hospitals of Hunan Province, in central China. The
      instruments usedin this study were Eysenck Personality Questionnaire Short Scale,
      ProfessionalIdentity Questionnaire, and Work-Related Depression, Anxiety and
      Irritation Scale.Extraversion and professional identity negatively correlated
      with and predictedwork-related depression, anxiety and irritation; Neuroticism
      and Psychoticismpositively correlated with and predicted work-related depression,
      anxiety andirritation. Strengthening the nurses' professional identity may be
      helpful towardreducing work-related depression, anxiety and irritation.
      Administrative andpsychological interventions of these work-related emotion
      problems should takethe difference in personality trait into account.

PMID- 29642308
TI  - Prevalence of Eosinophilic Esophagitis in Adult Patients with Upper
      Gastrointestinal Symptoms in a Locality in Upper Egypt.
AB  - BACKGROUND/AIMS: Eosinophilic esophagitis (EoE) is gaining importance in the
      diagnosis of upper gastrointestinal (UGI) symptoms. Diagnosis is based on the
      clinical presentation of esophageal dysfunction and pathological findings in the
      absence of other causes of tissue eosinophilia. Our study was designed to
      evaluate EoE prevalence in patients with UGI symptoms in our locality (El-Minia,
      Egypt). METHODS: This single-center, cross-sectional study recruited all patients
      with UGI symptoms who agreed for endoscopic evaluation. Esophageal biopsy samples
      were obtained and histological evaluation for the presence of eosinophils was
      performed for every patient. EoE was defined when at least 15 eosinophils were
      present in a single high-power field, in the absence of other causes of
      esophageal eosinophilia. RESULTS: Between 2013 and 2015, 218 of 476 adult
      patients with UGI symptoms underwent upper endoscopy after giving consent. Among
      the 218 patients, only 4 (1.87%) had the diagnosis of EoE based on the presence
      of eosinophils in esophageal biopsies and exclusion of other causes of esophageal
      eosinophilia. Three patients with EoE presented mainly with dysphagia (75%)
      and/or other UGI symptoms, such as heartburn. CONCLUSIONS: We observed a low
      prevalence of EoE in our locality. The diagnosis of EoE should be considered in
      patients with dysphagia and/or heartburn.

PMID- 29642309
TI  - SCREENING FOR TYPE 2 DIABETES MELLITUS AND PREDIABETES USING POINT-OF-CARE
      TESTING FOR HBA1C AMONG THAI DENTAL PATIENTS.
AB  - Diabetes mellitus type 2 (DM) is associated with oral diseases. Somestudies
      indicated that patients who seek dental treatment could have
      undiagnosedhyperglycemic condition. The aim of this study was to assess the
      prevalence ofundiagnosed hyperglycemia and selected associated factors among Thai
      dentalpatients. Dental patients without a history of hyperglycemia were recruited
      fromthe Special Clinic, Faculty of Dentistry, Mahidol University, Bangkok,
      Thailand andHis Majesty the King's Dental Service Unit, Thailand. The patients
      were randomlyselected and a standardized questionnaire was used to collect
      demographic datafrom each patient. Blood pressure, body mass index (BMI), and
      waist circumferencewere recorded for each subject. The number of missing teeth,
      periodontalstatus, and salivary flow rate were also investigated. HbA1c was
      assessed usinga finger prick blood sample and analyzed with a point-of-care
      testing machine.Hyperglycemia was defined as a HbA1c >=5.7%. The prevalence of
      hyperglycemiaamong participants was calculated and multivariate logistic
      regression analysiswas used to identify risk factors. A total of 724 participants
      were included in thestudy; 33.8% had hyperglycemia. On multiple logistic
      regression analysis, olderage, family history of DM, being overweight (BMI >=23
      kg/m2), having centralobesity and having severe periodontitis were significantly
      associated with hyperglycemia.The high prevalence of hyperglycemia in this study
      of dental patientssuggests this setting may be appropriate to screen for patients
      with hyperglycemia.

PMID- 29642310
TI  - DIET, BODY MASS INDEX AND DENTAL CARIES AMONG THAI CHILDREN AGED 3 TO 5 YEARS.
AB  - Early childhood caries (ECC) can cause pain and interfere with healthynutrition
      affecting a child growth. The aim of this study was to determine if thereis an
      association between dental caries and body mass index (BMI) among Thaichildren
      aged 3 to 5 years. We randomly selected 100 students attending SuanMissakawan
      School, Bangkok, Thailand. We examined each child to determine thenumber of
      decayed, missing and filled teeth (DMFT) giving a DMFT score. We alsomeasured the
      height and weight for each subject and calculated their body massindex (BMI) as
      weight in kilograms divided by height in meter squared. Parentsor guardians were
      asked to complete a questionnaire asking general informationand the diet of the
      child. Data from the questionnaire were analyzed using theKruskal-Wallis test.
      Associations between caries and variables were examinedusing the Spearman's
      correlation with significance set at p<0.05. The mean (+/-SD)age of the subject,
      the mean (+/-SD) DMFT score of the subject and the mean (+/-SD)BMI for the
      subjects were 4.21(+/-0.71) years old, 5.27(+/-4.78) and 16.46(+/-2.56) kg/m2,
      respectively. Seventy-one percent of subjects had a normal BMI, 25%
      wereoverweight and 4% were underweight. Eighteen percent had no caries
      (DMFTscore=0), 32% had a few caries (DMFT score=0.1-3.0), 14% had many caries
      (DMFTscores=3.1-6.9), and 36% had very many caries (DMFT>=7). The DMFT score
      wasnot significantly associated with a history of sugar consumption or BMI.
      TheDMFT score was significantly negatively associated with estimated fat
      consumptionand estimated iron consumption based on the diet reported by the
      parents orguardians. Further studies are needed to determine if these reported
      diets reflectactual consumption and if the associations are still significant.

PMID- 29642311
TI  - DENTAL PATIENT KNOWLEDGE ABOUT THE EFFECTS OF SMOKING AND ATTITUDES ABOUT THE
      ROLE OF DENTISTS IN SMOKING CESSATION.
AB  - Dentists can offer their patients who smoke tobacco assistance withsmoking
      cessation. We conducted this study to assess dental patient knowledgeabout the
      effects of smoking and perceptions and attitudes regarding the role ofdentists in
      smoking cessation counselling. We conducted this study to inform tobaccocessation
      programs that could potentially include dentists. We conducted across-sectional
      study using a self-administered questionnaire among 375 patients.The mean age of
      subjects was 33.4 years; females comprised 51.5%. Participantswere divided into 3
      groups: those who never smoked (n = 263, 70.7%), smokers (n= 92, 24.7%), and ex
      smokers (n = 17, 4.5%). Significantly more participants (p =0.046) who never
      smoked (92.9%) knew smoking can cause bad breath than smokers(86.9%).
      Significantly more participants (p = 0.002) who never smoked (74.8%)knew smoking
      can cause periodontal disease than smokers (57.6%). Significantlymore
      participants (p < 0.001) who never smoked (84.5%) knew smoking can causeoral
      cancer than smokers (66.7%). Significantly more participants (p < 0.001) whonever
      smoked (86.7%) knew smoking can cause lung cancer than smokers
      (69.7%).Significantly more participants who never smoked (85.5%) felt dentists
      should beinterested in the smoking status of their patients (p = 0.004) than
      smokers (72.6%).Significantly more participants (p = 0.08) who never smoked
      (69.6%) stated dentistsshould give smoking cessation advice than smokers/ex
      smokers (59.0%). Smoker/ex-smokers had less knowledge about the effects of
      smoking on oral and generalhealth than non-smokers. Both smokers/ex-smokers and
      non-smokers felt dentistsshould provide smoking cessation advice.

PMID- 29642312
TI  - EFFECTS OF SHORT-TERM USE OF XYLITOL CHEWING GUM AND MOLTITOL ORAL SPRAY ON
      SALIVARY STREPTOCOCCUS MUTANS AND ORAL PLAQUE.
AB  - The purpose of this study was to investigate the short-term effects ofxylitol
      chewing gum and maltitol spray on the concentration of salivary
      mutansstreptococci (MS) and on the plaque index. Eighty-one second, third and
      fourthyear dental and dental assistant students with a salivary MS concentration
      > 103CFU/ml cultured on mitis salivarius bacitracin (MSB) agar were included in
      thestudy. The age range of subjects was 18-23 years. The participants were
      dividedinto 3 groups: control, xylitol chewing gum and maltitol spray groups.
      Each subjectbrushed their teeth with fluoridated toothpaste (1,000 ppm). Each
      subject in thexylitol chewing gum group was told to chew 2 pieces, 6 times a day
      (total xylitoldose=7.3 g/day) for 4 weeks. Each subject in the maltitol spray
      group was told tospray one puff twice daily (morning and evening) for 4 weeks. A
      dental examinationand saliva samples to determine the salivary MS concentration
      were collectedat baseline and at 2 and 4 weeks after experiment initiation. The
      nonparametricMann-Whitney U test was used to analyze differences among groups.
      The meanages in the control, xylitol chewing gum and maltitol spray groups were
      22+/-1,20+/-1 and 20+/-1 years, respectively. The mean MS concentrations at the
      beginningof the study and after 2 weeks in the control, and xylitol chewing gum
      and moltitoloral spray groups were not significantly different from each other.
      There wasa significantly lower MS concentration in the moltitol oral spray group
      than inthe control group by 4 weeks (p=0.045) but no significant difference
      between thecontrol group and the xylitol gum group by 4 weeks. There were no
      significantdifferences in the mean plaque index at baseline among the control
      group, thexylitol chewing gum group and the moltitol oral spray group. The plaque
      indexwas significantly lower in the xylitol chewing gum group than the control
      group(p=0.003) at 2 weeks but not 4 weeks. There was no significant difference in
      themean plaque index between the control group and the moltitol oral spray
      groupat any time. Using the maltitol spray significantly reduced the MS level in
      thesaliva by 4 weeks use but using the xylitol gum did not. However, using the
      xylitolchewing gum did reduce the mean plaque by 2 weeks use but the effect did
      notlast; by 4 weeks there was no difference from control. The moltitol spray
      providedno benefit over the control in reducing the mean plaque index.

PMID- 29642313
TI  - ENHANCING REMINERALIZATION OF PRIMARY ENAMEL LESIONS WITH FLUORIDE DENTIFRICE
      CONTAINING TRICALCIUM PHOSPHATE.
AB  - Fluoride dentifrice is effective in preventive dental caries but may
      causefluorosis, especially in young children. Reducing the concentration of
      fluoride fromthe regular concentration of 1,000 parts per million (ppm) to 500
      ppm can reducethe risk for fluorosis but increases the risk of caries. Adding
      tricalcium phosphate(TCP) to the dentifrices may improve the efficacy of
      remineralization possiblyallowing for a lower concentration of fluoride to reduce
      the risk of fluorosis. Westudied this to inform future caries prevention efforts
      in children. We immersed40 sound primary incisors into demineralizing solution
      (pH=4.4) for 96 hours at37 degrees C to create demineralized lesions. The 40
      teeth were then divided into 4 groupsof 10 teeth each. Group A: control (treated
      with deionized water only); Group B:treated with fluoride dentifrice at a
      concentration of 1,000 ppm; Group C: treatedwith fluoride dentifrice at a
      concentration of 500 ppm and 500 ppm TCP, andGroup D: treated with fluoride
      dentifrice at a concentration of 1,000 ppm and 500ppm TCP. The teeth were each
      subjected to 7 days of pH-cycling and the studieddentifrice was applied for one
      minute, 3 times daily during the 7 day period. Afterthe 7 day period the teeth
      were each sectioned and examined with polarized lightmicroscopy. The depths of
      demineralized areas were measured using Image-Proplus software. A pair t-test was
      used to compare lesion depths before and afterdentifrice treatment. Differences
      in mean lesion depths within each group wereanalyzed using the One-way ANOVA and
      LSD tests; a 95% confidence intervalswere calculated. The mean lesion depths in
      all the groups before dentifrice treatmentwere not significantly different
      (p=0.143). The mean demineralized lesiondepths after dentifrice treatment were
      significantly different by group (p=0.00).The mean demineralized lesion depth in
      Group A significantly deeper than theother groups (p=0.00). Group D had the
      shallowest depth, significantly shallowerthan the other groups (p=0.006). There
      was no significant difference in themean demineralized lesion depth between
      Groups B and C (p=0.478). The meandemineralized lesion depth changed
      significantly after dentifrice treatment in allthe groups (p=0.00). Group A was
      significantly deeper (p=0.00) and groups B, Cand D were all significantly
      shallow. Group D had the greatest reduction in meandemineralized lesion depth
      (p<0.05). The 1,000 ppm fluoride plus TCP dentifricegave superior
      remineralization than the 500 ppm fluoride plus TCP and the 1,000ppm fluoride
      dentifrice. The 500 ppm fluoride plus TCP gave the same remineralizingeffect as
      the 1,000 ppm fluoride dentifrice. TCP enhances remineralizationon primary enamel
      when added to fluoride dentifrice. Our results show if TCP isadded to fluoride
      dentifrice a lower concentration of fluoride is needed to providethe same benefit
      as fluoride dentifrice with a higher concentration of fluoride,reducing the risk
      of fluorosis in children.

PMID- 29642314
TI  - Re: Examining the Value of Video Visits to Patients in an Outpatient Urology
      Clinic.

PMID- 29642315
TI  - Re: Comparing Clinical and Economic Outcomes Associated with Early Initiation of
      Combination Therapy of an Alpha Blocker and Dutasteride or Finasteride in Men
      with Benign Prostatic Hyperplasia in the United States.

PMID- 29642316
TI  - Re: Medical Treatment of Nocturia in Men with Lower Urinary Tract Symptoms:
      Systematic Review by the European Association of Urology Guidelines Panel for
      Male Lower Urinary Tract Symptoms.

PMID- 29642317
TI  - Re: Alvimopan for Recovery of Bowel Function after Radical Cystectomy.

PMID- 29642318
TI  - Re: Use of Adjuvant Chemotherapy in Radical Cystectomy Patients Aged >65 Years: A
      Population-Based Study from the Surveillance Epidemiology and End Results (SEER)
      Medicare Database.

PMID- 29642319
TI  - Re: Clinical Characteristics, Beliefs, and Coping Strategies among Older Patients
      with Overactive Bladder.

PMID- 29642320
TI  - Re: Frontal Lobe Function Correlates with One-Year Incidence of Urinary
      Incontinence in Elderly with Alzheimer Disease.

PMID- 29642321
TI  - Re: Qualitative Exploration of the Patient Experience of Underactive Bladder.

PMID- 29642322
TI  - Re: Nocturia Increases the Incidence of Depressive Symptoms: A Longitudinal Study
      of the HEIJO-KYO Cohort.

PMID- 29642323
TI  - Re: Functional and Targeted Lymph Node Imaging in Prostate Cancer: Current Status
      and Future Challenges.

PMID- 29642324
TI  - Re: Symptomatic Treatment of Uncomplicated Lower Urinary Tract Infections in the
      Ambulatory Setting: Randomised, Double Blind Trial.

PMID- 29642325
TI  - Re: Selective Depletion of Uropathogenic E. coli from the Gut by a FimH
      Antagonist.

PMID- 29642326
TI  - Re: Robotic Salvage Retroperitoneal and Pelvic Lymph Node Dissection for 'Node
      Only' Recurrent Prostate Cancer: Technique and Initial Series.

PMID- 29642327
TI  - Re: A Pragmatic Randomized Controlled Trial Examining the Impact of the Retzius
      Sparing Approach on Early Urinary Continence Recovery after Robot-Assisted
      Radical Prostatectomy.

PMID- 29642328
TI  - Re: Sexual Dysfunction is Associated with Suicidal Ideation in Female Service
      Members and Veterans.

PMID- 29642329
TI  - Re: Robot Assisted Laparoscopic Radical Prostatectomy: Assistant's Seniority has
      No Influence on Perioperative Course.

PMID- 29642330
TI  - Re: Factors Associated with Specific Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition. Sexual Dysfunctions in Breast Cancer Survivors: A
      Study of Patients and Their Partners.

PMID- 29642332
TI  - Re: Non-Alcoholic Fatty Liver Disease as a Risk Factor for Female Sexual
      Dysfunction in Premenopausal Women.

PMID- 29642331
TI  - Re: Randomized Trial of Clitoral Vacuum Suction versus Vibratory Stimulation in
      Neurogenic Female Orgasmic Dysfunction.

PMID- 29642333
TI  - Re: Fertility Outcomes after Extended Searches for Ejaculated Spermatozoa in Men
      with Virtual Azoospermia.

PMID- 29642334
TI  - Re: Effect of Cranial Irradiation on Sperm Concentration of Adult Survivors of
      Childhood Acute Lymphoblastic Leukemia: A Report from the St. Jude Lifetime
      Cohort Study.

PMID- 29642335
TI  - Re: Transurethral Resection of Ejaculatory Ducts: A Step-by-Step Guide.

PMID- 29642336
TI  - Re: Efficacy of Standardized Nursing Fertility Counseling on Sperm Banking Rates
      in Cancer Patients.

PMID- 29642337
TI  - Re: Validation Study of the SCREENIVF: An Instrument to Screen Women or Men on
      Risk for Emotional Maladjustment before the Start of a Fertility Treatment.

PMID- 29642338
TI  - Re: Long-Term Functional Outcomes after Penoscrotal Hypospadias Repair: A
      Retrospective Comparative Study of Proximal TIP, Onlay, and Duckett.

PMID- 29642339
TI  - Re: Standardized Process to Improve Patient Flow from the Emergency Room to the
      Operating Room for Pediatric Patients with Testicular Torsion.

PMID- 29642340
TI  - Re: State Appellant Cases for Testicular Torsion: Case Review from 1985 to 2015.

PMID- 29642341
TI  - Re: Biometry of the Hypospadic Penis after Hormone Therapy (Testosterone and
      Estrogen): A Randomized, Double-Blind Controlled Trial.

PMID- 29642343
TI  - Re: A 22-Year Retrospective Study: Educational Update and New Referral Pattern of
      Age at Orchidopexy.

PMID- 29642342
TI  - Re: New Insights into the Alleged Kidney Donor Profile Index Labeling Effect on
      Kidney Utilization.

PMID- 29642344
TI  - Re: Narrow Networks on the Health Insurance Marketplaces: Prevalence, Pricing,
      and the Cost of Network Breadth.

PMID- 29642345
TI  - Re: Sustained Gains in Coverage, Access, and Affordability under the ACA: A 2017
      Update.

PMID- 29642346
TI  - Re: Americans Support Price Shopping for Health Care, but Few Actually Seek out
      Price Information.

PMID- 29642347
TI  - Re: Outcomes of Urethroplasty to Treat Urethral Strictures Arising from
      Artificial Urinary Sphincter Erosions and Rates of Subsequent Device Replacement.

PMID- 29642348
TI  - Re: Transobturator Sling for Post-Prostatectomy Incontinence: Radiation's Effect
      on Efficacy/Satisfaction.

PMID- 29642349
TI  - Re: Inflatable Penile Prosthesis as Tissue Expander: What is the Evidence?

PMID- 29642350
TI  - Re: Associating Mutations Causing Cystinuria with Disease Severity with the Aim
      of Providing Precision Medicine.

PMID- 29642351
TI  - Re: Plasma Oxalate in Relation to eGFR in Patients with Primary Hyperoxaluria,
      Enteric Hyperoxaluria and Urinary Stone Disease.

PMID- 29642352
TI  - Re: Oxalobacter formigenes-Associated Host Features and Microbial Community
      Structures Examined Using the American Gut Project.

PMID- 29642353
TI  - Re: Dual Energy CT Kidney Stone Differentiation in Photon Counting Computed
      Tomography.

PMID- 29642354
TI  - Re: Impact of Diagnostic Ureteroscopy on Intravesical Recurrence in Patients
      Undergoing Radical Nephroureterectomy for Upper Tract Urothelial Cancer: A
      Systematic Review and Meta-Analysis.

PMID- 29642355
TI  - Re: Defining the Role of Intraoperative Transesophageal Echocardiography during
      Radical Nephrectomy with Inferior Vena Cava Tumor Thrombectomy for Renal Cell
      Carcinoma.

PMID- 29642356
TI  - Re: Comparative Effectiveness of Treatment Strategies for Bladder Cancer with
      Clinical Evidence of Regional Lymph Node Involvement.

PMID- 29642357
TI  - Re: Phase III, Double-Blind, Randomized Trial that Compared Maintenance Lapatinib
      versus Placebo after First-Line Chemotherapy in Patients with Human Epidermal
      Growth Factor Receptor 1/2-Positive Metastatic Bladder Cancer.

PMID- 29642358
TI  - Re: Health-Related Quality of Life for Immediate versus Delayed Androgen
      Deprivation Therapy in Patients with Asymptomatic, Non-Curable Prostate Cancer
      (TROG 03.06 and VCOG PR 01-03 [TOAD]): A Randomised, Multicentre, Non-Blinded,
      Phase 3 Trial.

PMID- 29642359
TI  - Re: Cabazitaxel versus Docetaxel as First-Line Therapy for Patients with
      Metastatic Castration-Resistant Prostate Cancer: A Randomized Phase III Trial
      FIRSTANA.

PMID- 29642360
TI  - Re: Post-Chemotherapy Retroperitoneal Teratoma in Nonseminomatous Germ Cell
      Tumors: Do Predictive Factors Exist? Results from a National Multicenter Study.

PMID- 29642361
TI  - Re: Enterobacteria Secrete an Inhibitor of Pseudomonas Virulence during Clinical
      Bacteriuria.

PMID- 29642362
TI  - Re: Prostate Cancer-Associated SPOP Mutations Confer Resistance to BET Inhibitors
      through Stabilization of BRD4.

PMID- 29642363
TI  - Re: A CCR4 Antagonist Reverses the Tumor-Promoting Microenvironment of Renal
      Cancer.

PMID- 29642364
TI  - Re: Characterization of Lower Urinary Tract Symptoms in Patients with Idiopathic
      Normal Pressure Hydrocephalus.

PMID- 29642365
TI  - Re: Long-Term Outcomes of Intravesical Dimethyl Sulfoxide/Heparin/Hydrocortisone
      Therapy for Interstitial Cystitis/Bladder Pain Syndrome.

PMID- 29642366
TI  - Re: Detailed Analysis of Adverse Events and Surgical Interventions in a Large
      Prospective Trial of Sacral Neuromodulation Therapy for Overactive Bladder
      Patients.

PMID- 29642367
TI  - Re: Dietary Sodium Restriction Reduces Nocturnal Urine Volume and Nocturnal
      Polyuria Index in Renal Allograft Recipients with Nocturnal Polyuria.

PMID- 29642368
TI  - Re: Effectiveness of BTX-A and Neuromodulation in Treating OAB with or without
      Detrusor Overactivity: A Systematic Review.

PMID- 29642369
TI  - Bis-Indolyl Benzenoids, Hydroxypyrrolidine Derivatives and Other Constituents
      from Cultures of the Marine Sponge-Associated Fungus Aspergillus candidus
      KUFA0062.
AB  - A previously unreported bis-indolyl benzenoid, candidusin D (2e) and a new
      hydroxypyrrolidine alkaloid, preussin C (5b) were isolated together with fourteen
      previously described compounds: palmitic acid, clionasterol, ergosterol 5,8
      endoperoxides, chrysophanic acid (1a), emodin (1b), six bis-indolyl benzenoids
      including asterriquinol D dimethyl ether (2a), petromurin C (2b), kumbicin B
      (2c), kumbicin A (2d), 2"-oxoasterriquinol D methyl ether (3), kumbicin D (4),
      the hydroxypyrrolidine alkaloid preussin (5a), (3S, 6S)-3,6-dibenzylpiperazine
      2,5-dione (6) and 4-(acetylamino) benzoic acid (7), from the cultures of the
      marine sponge-associated fungus Aspergillus candidus KUFA 0062. Compounds 1a, 2a
      e, 3, 4, 5a-b, and 6 were tested for their antibacterial activity against Gram
      positive and Gram-negative reference and multidrug-resistant strains isolated
      from the environment. Only 5a exhibited an inhibitory effect against S. aureus
      ATCC 29213 and E. faecalis ATCC29212 as well as both methicillin-resistant S.
      aureus (MRSA) and vancomycin-resistant enterococci (VRE) strains. Both 1a and 5a
      also reduced significant biofilm formation in E. coli ATCC 25922. Moreover, 2b
      and 5a revealed a synergistic effect with oxacillin against MRSA S. aureus 66/1
      while 5a exhibited a strong synergistic effect with the antibiotic colistin
      against E. coli 1410/1. Compound 1a, 2a-e, 3, 4, 5a-b, and 6 were also tested,
      together with the crude extract, for cytotoxic effect against eight cancer cell
      lines: HepG2, HT29, HCT116, A549, A 375, MCF-7, U-251, and T98G. Except for 1a,
      2a, 2d, 4, and 6, all the compounds showed cytotoxicity against all the cancer
      cell lines tested.

PMID- 29642370
TI  - Global Transcriptome Analysis of Brown Adipose Tissue of Diet-Induced Obese Mice.
AB  - Consumption of a high-fat diet (HFD) promotes the development of obesity, a
      disease resulting from an imbalance between energy intake and energy expenditure.
      Brown adipose tissue (BAT) has thermogenic capacity that burns calories to
      produce heat, and it is a potential target for the treatment and prevention of
      obesity. There is limited information regarding the impact of HFD on the BAT
      transcriptome. We hypothesized that HFD-induced obesity would lead to
      transcriptional regulation of BAT genes. RNA sequencing was used to generate
      global transcriptome profiles from BAT of lean mice fed with a low-fat diet (LFD)
      and obese mice fed with a HFD. Gene Ontology (GO) analysis identified increased
      expression of genes involved in biological processes (BP) related to immune
      responses, which enhanced molecular function (MF) in chemokine activity;
      decreased expression of genes involved in BP related to ion transport and muscle
      structure development, which reduced MF in channel and transporter activity and
      structural binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) functional
      pathway analysis indicated that pathways associated with innate immunity were
      enhanced by HFD, while pathways associated with muscle contraction and calcium
      signaling were suppressed by HFD. Collectively, these results suggest that diet
      induced obesity changes transcriptomic signatures of BAT, leading to dysfunction
      involving inflammation, calcium signaling, ion transport, and cell structural
      development.

PMID- 29642371
TI  - Fairness-Based Tasks for Assessing Children's Perceptions of Food Quantities and
      Associations with Portion Selection.
AB  - It is critical to develop ecologically valid experimental methods to assess
      consumers' food-related behaviors. Ad libitum approaches are often used but may
      not be appropriate for studies with children or with products that are not
      typically consumed until the individual feels full. The current study presents
      novel methods to assess children's size perception and portion preference for
      gummy candies. In the first study, 62 children (30 boys, 32 girls) aged 6 to 9
      years completed two matching tasks: one using pictures on a computer screen, and
      a similar task where the products were physically manipulated. Results of the two
      matching tasks were correlated, demonstrating that a computer-based approach
      could be used to predict the factors influencing children's perception of food
      amount: the number, size, and shape of pieces. In the second study, a portioning
      measure was developed to investigate whether the factors identified in the
      matching tasks were confirmed in a task that more closely represented portion
      selection in the real world. The effects observed in the matching tasks could not
      be replicated in the portioning task. The size of each item had no significant
      impact on the portion selection, suggesting that it may be possible to reduce the
      size of pieces in snacks where multiple pieces are typically consumed without
      negatively impacting perceived quantity in children, thus offering a promising
      strategy to nudge children toward choosing smaller portions.

PMID- 29642372
TI  - omega-3 and omega-6 Fatty Acids Modulate Conventional and Atypical Protein Kinase
      C Activities in a Brain Fatty Acid Binding Protein Dependent Manner in
      Glioblastoma Multiforme.
AB  - Glioblastoma multiforme (GBM) is a highly infiltrative brain cancer with a dismal
      prognosis. High levels of brain fatty acid binding protein (B-FABP) are
      associated with increased migration/infiltration in GBM cells, with a high ratio
      of arachidonic acid (AA) to docosahexaenoic acid (DHA) driving B-FABP-mediated
      migration. Since several protein kinase Cs (PKCs) are overexpressed in GBM and
      linked to migration, we explored a possible relationship between B-FABP and
      levels/activity of different PKCs, as a function of AA and DHA supplementation.
      We report that ectopic expression of B-FABP in U87 cells alters the levels of
      several PKCs, particularly PKCzeta. Upon analysis of PKCzeta RNA levels in a
      panel of GBM cell lines and patient-derived GBM neurospheres, we observed a trend
      towards moderate positive correlation (r = 0.624, p = 0.054) between B-FABP and
      PKCzeta RNA levels. Analysis of PKC activity in U87 GBM cells revealed decreased
      typical PKC activity (23.4%) in B-FABP-expressing cells compared with
      nonexpressing cells, with no difference in novel and atypical PKC activities. AA
      and DHA modulated both conventional and atypical PKC activities in a B-FABP
      dependent manner, but had no effect on novel PKC activity. These results suggest
      that conventional and atypical PKCs are potential downstream effectors of B
      FABP/fatty acid-mediated alterations in GBM growth properties.

PMID- 29642373
TI  - Oil Motion Control by an Extra Pinning Structure in Electro-Fluidic Display.
AB  - Oil motion control is the key for the optical performance of electro-fluidic
      displays (EFD). In this paper, we introduced an extra pinning structure (EPS)
      into the EFD pixel to control the oil motion inside for the first time. The
      pinning structure canbe fabricated together with the pixel wall by a one-step
      lithography process. The effect of the relative location of the EPS in pixels on
      the oil motion was studied by a series of optoelectronic measurements. EPS showed
      good control of oil rupture position. The properly located EPS effectively guided
      the oil contraction direction, significantly accelerated switching on process,
      and suppressed oil overflow, without declining in aperture ratio. An
      asymmetrically designed EPS off the diagonal is recommended. This study provides
      a novel and facile way for oil motion control within an EFD pixel in both
      direction and timescale.

PMID- 29642374
TI  - Cancer Mortality in Residents of the Cadmium-Polluted Jinzu River Basin in
      Toyama, Japan.
AB  - After 26 years, we followed up 7348 participants in a 1979-1984 health screening
      survey in the Jinzu River basin, the heaviest cadmium-polluted area in Japan. We
      assessed the associations of cadmium exposure levels and mortality from cancer
      and renal damage, indicated by records of proteinuria and glucosuria in the
      original survey. Mortality risks (hazard ratios) were analyzed using the Cox
      proportional hazards model, stratified by sex, after adjusting for age, smoking
      status, and hypertension, as indicated in the original survey records. In men,
      the adjusted hazard ratio for mortality from lung cancer was significantly lower
      in individuals residing in an area of historically high cadmium exposure and in
      subjects with a historical record of proteinuria, glucosuria, and
      glucoproteinuria. The risk of mortality from prostate cancer was borderline
      higher in cadmium-exposed men. In women, historical cadmium exposure was not
      associated with an increased risk of mortality from malignant neoplasms, but the
      adjusted hazard ratios for death from total malignant neoplasms or from renal and
      uterine cancers were significantly higher in exposed subjects with a historical
      record of proteinuria, glucosuria, and glucoproteinuria. These findings suggest
      that women residing in cadmium-polluted areas who exhibit markers of renal damage
      may be at risk of dying of cancer.

PMID- 29642375
TI  - Molecular Characterization of Gastric Epithelial Cells Using Flow Cytometry.
AB  - The ability to analyze individual epithelial cells in the gastric mucosa would
      provide important insight into gastric disease, including chronic gastritis and
      progression to gastric cancer. However, the successful isolation of viable
      gastric epithelial cells (parietal cells, neck cells, chief cells, and foveolar
      cells) from gastric glands has been limited due to difficulties in tissue
      processing. Furthermore, analysis and interpretation of gastric epithelial cell
      flow cytometry data has been difficult due to the varying sizes and light scatter
      properties of the different epithelial cells, high levels of autofluorescence,
      and poor cell viability. These studies were designed to develop a reliable method
      for isolating viable single cells from the corpus of stomachs and to optimize
      analyses examining epithelial cells from healthy and diseased stomach tissue by
      flow cytometry. We performed a two stage enzymatic digestion in which collagenase
      released individual gastric glands from the stromal tissue of the corpus,
      followed by a Dispase II digestion that dispersed these glands into greater than
      1 * 106 viable single cells per gastric corpus. Single cell suspensions were
      comprised of all major cell lineages found in the normal gastric glands. A method
      describing light scatter, size exclusion, doublet discrimination, viability
      staining, and fluorescently-conjugated antibodies and lectins was used to analyze
      individual epithelial cells and immune cells. This technique was capable of
      identifying parietal cells and revealed that gastric epithelial cells in the
      chronically inflamed mucosa significantly upregulated major histocompatibility
      complexes (MHC) I and II but not CD80 or CD86, which are costimulatory molecules
      involved in T cell activation. These studies describe a method for isolating
      viable single cells and a detailed description of flow cytometric analysis of
      cells from healthy and diseased stomachs. These studies begin to identify effects
      of chronic inflammation on individual gastric epithelial cells, a critical
      consideration for the study of gastric cancer.

PMID- 29642376
TI  - Transgenic Xenopus laevis Line for In Vivo Labeling of Nephrons within the
      Kidney.
AB  - Xenopus laevis embryos are an established model for studying kidney development.
      The nephron structure and genetic pathways that regulate nephrogenesis are
      conserved between Xenopus and humans, allowing for the study of human disease
      causing genes. Xenopus embryos are also amenable to large-scale screening, but
      studies of kidney disease-related genes have been impeded because assessment of
      kidney development has largely been limited to examining fixed embryos. To
      overcome this problem, we have generated a transgenic line that labels the
      kidney. We characterize this cdh17:eGFP line, showing green fluorescent protein
      (GFP) expression in the pronephric and mesonephric kidneys and colocalization
      with known kidney markers. We also demonstrate the feasibility of live imaging of
      embryonic kidney development and the use of cdh17:eGFP as a kidney marker for
      secretion assays. Additionally, we develop a new methodology to isolate and
      identify kidney cells for primary culture. We also use morpholino knockdown of
      essential kidney development genes to establish that GFP expression enables
      observation of phenotypes, previously only described in fixed embryos. Taken
      together, this transgenic line will enable primary kidney cell culture and live
      imaging of pronephric and mesonephric kidney development. It will also provide a
      simple means for high-throughput screening of putative human kidney disease
      causing genes.

PMID- 29642377
TI  - Benzodiazepines Withdrawal: Initial Outcomes and Long-Term Impact on Falls in a
      French Nursing Home.
AB  - Long-term use of benzodiazepines (BZDs) is known to induce tolerance and
      dependence, and increase the risk of falls-related injuries in older adults. We
      present a study carried out in a French nursing home that concerns the
      implementation of a BZD withdrawal program reassessed at one year. BZD
      deprescription was achieved by gradual cessation of doses. A secondary benefit of
      this program was assessed by comparing the number of falls among residents before
      and after withdrawal. The number of falls was recorded over a six-month period
      prior to the onset of withdrawal (T1) and then over a six-month period after
      reassessment at one year (T2). At the beginning, 31 (28.7%) of the patients were
      under BZD. Total deprescription was obtained for 11 patients. The number of falls
      per patient over the T1 period was not different between the two groups (future
      non-withdrawn and withdrawn patients in BZD): 2.1 +/- 1.3 and 2.3 +/- 0.6 falls
      per resident, respectively. Conversely, the number of falls per patient was
      significantly decreased in the population completely withdrawn in BZD between the
      T1 and T2 periods (2.3 +/- 0.6 vs. 0.5 +/- 0.2 falls, p = 0.01). The results show
      that BZD deprescription, through a gradual reduction of doses, is possible to
      achieve.

PMID- 29642379
TI  - Surface Nanocrystallization and Amorphization of Dual-Phase TC11 Titanium Alloys
      under Laser Induced Ultrahigh Strain-Rate Plastic Deformation.
AB  - As an innovative surface technology for ultrahigh strain-rate plastic
      deformation, laser shock peening (LSP) was applied to the dual-phase TC11
      titanium alloy to fabricate an amorphous and nanocrystalline surface layer at
      room temperature. X-ray diffraction, transmission electron microscopy, and high
      resolution transmission electron microscopy (HRTEM) were used to investigate the
      microstructural evolution, and the deformation mechanism was discussed. The
      results showed that a surface nanostructured surface layer was synthesized after
      LSP treatment with adequate laser parameters. Simultaneously, the behavior of
      dislocations was also studied for different laser parameters. The rapid slipping,
      accumulation, annihilation, and rearrangement of dislocations under the laser
      induced shock waves contributed greatly to the surface nanocrystallization. In
      addition, a 10 nm-thick amorphous structure layer was found through HRTEM in the
      top surface and the formation mechanism was attributed to the local temperature
      rising to the melting point, followed by its subsequent fast cooling.

PMID- 29642378
TI  - Pasture Feeding Changes the Bovine Rumen and Milk Metabolome.
AB  - The purpose of this study was to examine the effects of two pasture feeding
      systems-perennial ryegrass (GRS) and perennial ryegrass and white clover (CLV)
      and an indoor total mixed ration (TMR) system on the (a) rumen microbiome; (b)
      rumen fluid and milk metabolome; and (c) to assess the potential to distinguish
      milk from different feeding systems by their respective metabolomes. Rumen fluid
      was collected from nine rumen cannulated cows under the different feeding systems
      in early, mid and late lactation, and raw milk samples were collected from ten
      non-cannulated cows in mid-lactation from each of the feeding systems. The
      microbiota present in rumen liquid and solid portions were analysed using 16S
      rRNA gene sequencing, while 1H-NMR untargeted metabolomic analysis was performed
      on rumen fluid and raw milk samples. The rumen microbiota composition was not
      found to be significantly altered by any feeding system in this study, likely as
      a result of a shortened adaptation period (two weeks' exposure time). In
      contrast, feeding system had a significant effect on both the rumen and milk
      metabolome. Increased concentrations of volatile fatty acids including acetic
      acid, an important source of energy for the cow, were detected in the rumen of
      TMR and CLV-fed cows. Pasture feeding resulted in significantly higher
      concentrations of isoacids in the rumen. The ruminal fluids of both CLV and GRS
      fed cows were found to have increased concentrations of p-cresol, a product of
      microbiome metabolism. CLV feeding resulted in increased rumen concentrations of
      formate, a substrate compound for methanogenesis. The TMR feeding resulted in
      significantly higher rumen choline content, which contributes to animal health
      and milk production, and succinate, a product of carbohydrate metabolism. Milk
      and rumen-fluids were shown to have varying levels of dimethyl sulfone in each
      feeding system, which was found to be an important compound for distinguishing
      between the diets. CLV feeding resulted in increased concentrations of milk urea.
      Milk from pasture-based feeding systems was shown to have significantly higher
      concentrations of hippuric acid, a potential biomarker of pasture-derived milk.
      This study has demonstrated that 1H-NMR metabolomics coupled with multivariate
      analysis is capable of distinguishing both rumen-fluid and milk derived from cows
      on different feeding systems, specifically between indoor TMR and pasture-based
      diets used in this study.

PMID- 29642380
TI  - Low-Cost GRIN-Lens-Based Nephelometric Turbidity Sensing in the Range of 0.1-1000
      NTU.
AB  - Turbidity sensing is very common in the control of drinking water. Furthermore,
      turbidity measurements are applied in the chemical (e.g., process monitoring),
      pharmaceutical (e.g., drug discovery), and food industries (e.g., the filtration
      of wine and beer). The most common measurement technique is nephelometric
      turbidimetry. A nephelometer is a device for measuring the amount of scattered
      light of suspended particles in a liquid by using a light source and a light
      detector orientated in 90 degrees  to each other. Commercially available
      nephelometers cost usually-depending on the measurable range, reliability, and
      precision-thousands of euros. In contrast, our new developed GRIN-lens-based
      nephelometer, called GRINephy, combines low costs with excellent reproducibility
      and precision, even at very low turbidity levels, which is achieved by its
      ability to rotate the sample. Thereby, many cuvette positions can be measured,
      which results in a more precise average value for the turbidity calculated by an
      algorithm, which also eliminates errors caused by scratches and contaminations on
      the cuvettes. With our compact and cheap Arduino-based sensor, we are able to
      measure in the range of 0.1-1000 NTU and confirm the ISO 7027-1:2016 for low
      turbidity values.

PMID- 29642381
TI  - Decision Tree Approach to the Impact of Parents' Oral Health on Dental Caries
      Experience in Children: A Cross-Sectional Study.
AB  - Decision tree (DT) analysis was applied in this cross-sectional study to
      investigate caries experience in children by using clinical and microbiological
      data obtained from parent-child pairs. Thirty pairs of parents and children were
      recruited from periodontal and pediatric dental clinics. All participants were
      clinically examined for caries and periodontitis by a calibrated examiner.
      Cariogenic and periodontopathic bacteria examinations were conducted. The Kendall
      rank correlation coefficient was used to measure the association between data
      variables obtained through clinical and microbiological examinations. A
      classificatory inductive decision tree was generated using the C4.5 algorithm
      with the top-down approach. The C4.5 DT analysis was applied to classify major
      influential factors for children dental caries experience. The DT identified
      parents' periodontal health classification, decayed, missing, filled permanent
      teeth (DMFT) index, periodontopathic test (PerioCheck) result, and periodontal
      pocket depth as the classification factors for children caries experience. 13.3%
      of children were identified with a low decayed, missing, filled primary teeth
      (dmft) index (dmft < 3) whose parents had a periodontal pocket depth <=3.7,
      PerioCheck score >1, DMFT index <13.5, and periodontal classification >2. The DT
      model for this study sample had an accuracy of 93.33%. Here, parental periodontal
      status and parents' DMFT were the factors forming the DT for children's caries
      experience.

PMID- 29642382
TI  - A Low Glycaemic Index Diet in Pregnancy Induces DNA Methylation Variation in
      Blood of Newborns: Results from the ROLO Randomised Controlled Trial.
AB  - The epigenetic profile of the developing fetus is sensitive to environmental
      influence. Maternal diet has been shown to influence DNA methylation patterns in
      offspring, but research in humans is limited. We investigated the impact of a low
      glycaemic index dietary intervention during pregnancy on offspring DNA
      methylation patterns using a genome-wide methylation approach. Sixty neonates
      were selected from the ROLO (Randomised cOntrol trial of LOw glycaemic index diet
      to prevent macrosomia) study: 30 neonates from the low glycaemic index
      intervention arm and 30 from the control, whose mothers received no specific
      dietary advice. DNA methylation was investigated in 771,484 CpG sites in free DNA
      from cord blood serum. Principal component analysis and linear regression were
      carried out comparing the intervention and control groups. Gene clustering and
      pathway analysis were also explored. Widespread variation was identified in the
      newborns exposed to the dietary intervention, accounting for 11% of the total
      level of DNA methylation variation within the dataset. No association was found
      with maternal early-pregnancy body mass index (BMI), infant sex, or birthweight.
      Pathway analysis identified common influences of the intervention on gene
      clusters plausibly linked to pathways targeted by the intervention, including
      cardiac and immune functioning. Analysis in 60 additional samples from the ROLO
      study failed to replicate the original findings. Using a modest-sized discovery
      sample, we identified preliminary evidence of differential methylation in progeny
      of mothers exposed to a dietary intervention during pregnancy.

PMID- 29642383
TI  - AlgM4: A New Salt-Activated Alginate Lyase of the PL7 Family with Endolytic
      Activity.
AB  - Alginate lyases are a group of enzymes that catalyze the depolymerization of
      alginates into oligosaccharides or monosaccharides. These enzymes have been
      widely used for a variety of purposes, such as producing bioactive
      oligosaccharides, controlling the rheological properties of polysaccharides, and
      performing structural analyses of polysaccharides. The algM4 gene of the marine
      bacterium Vibrio weizhoudaoensis M0101 encodes an alginate lyase that belongs to
      the polysaccharide lyase family 7 (PL7). In this study, the kinetic constants
      Vmax (maximum reaction rate) and Km (Michaelis constant) of AlgM4 activity were
      determined as 2.75 nmol/s and 2.72 mg/mL, respectively. The optimum temperature
      for AlgM4 activity was 30  degrees C, and at 70  degrees C, AlgM4 activity
      dropped to 11% of the maximum observed activity. The optimum pH for AlgM4
      activity was 8.5, and AlgM4 was completely inactive at pH 11. The addition of 1
      mol/L NaCl resulted in a more than sevenfold increase in the relative activity of
      AlgM4. The secondary structure of AlgM4 was altered in the presence of NaCl,
      which caused the alpha-helical content to decrease from 12.4 to 10.8% and the
      beta-sheet content to decrease by 1.7%. In addition, NaCl enhanced the thermal
      stability of AlgM4 and increased the midpoint of thermal denaturation (Tm) by 4.9
      degrees C. AlgM4 exhibited an ability to degrade sodium alginate, poly
      mannuronic acid (polyM), and poly-guluronic acid (polyG), resulting in the
      production of oligosaccharides with a degree of polymerization (DP) of 2-9. AlgM4
      possessed broader substrate, indicating that it is a bifunctional alginate lyase.
      Thus, AlgM4 is a novel salt-activated and bifunctional alginate lyase of the PL7
      family with endolytic activity.

PMID- 29642384
TI  - Tracking the Continuous Evolutionary Processes of an Endogenous Retrovirus of the
      Domestic Cat: ERV-DC.
AB  - An endogenous retrovirus (ERV) is a remnant of an ancient retroviral infection in
      the host genome. Although most ERVs have lost their viral productivity, a few
      ERVs retain their replication capacity. In addition, partially inactivated ERVs
      can present a potential risk to the host via their encoded virulence factors or
      the generation of novel viruses by viral recombination. ERVs can also eventually
      acquire a biological function, and this ability has been a driving force of host
      evolution. Therefore, the presence of an ERV can be harmful or beneficial to the
      host. Various reports about paleovirology have revealed each event in ERV
      evolution, but the continuous processes of ERV evolution over millions of years
      are mainly unknown. A unique ERV family, ERV-DC, is present in the domestic cat
      (Felis silvestriscatus) genome. ERV-DC proviruses are phylogenetically classified
      into three genotypes, and the specific characteristics of each genotype have been
      clarified: their capacity to produce infectious viruses; their recombination with
      other retroviruses, such as feline leukemia virus or RD-114; and their biological
      functions as host antiviral factors. In this review, we describe ERV-DC-related
      phenomena and discuss the continuous changes in the evolution of this ERV in the
      domestic cat.

PMID- 29642385
TI  - MicroRNAs as Potential Mediators for Cigarette Smoking Induced Atherosclerosis.
AB  - Smoking increases the risk of atherosclerosis-related events, such as myocardial
      infarction and ischemic stroke. Recent studies have examined the expression
      levels of altered microRNAs (miRNAs) in various diseases. The profiles of tissue
      miRNAs can be potentially used in diagnosis or prognosis. However, there are
      limited studies on miRNAs following exposure to cigarette smoke (CS). The present
      study was designed to dissect the effects and cellular/molecular mechanisms of CS
      induced atherosclerogenesis. Apolipoprotein E knockout (ApoE KO) mice were
      exposed to CS for five days a week for two months at low (two puffs/min for 40
      min/day) or high dose (two puffs/min for 120 min/day). We measured the area of
      atherosclerotic plaques in the aorta, representing the expression of miRNAs after
      the exposure period. Two-month exposure to the high dose of CS significantly
      increased the plaque area in aortic arch, and significantly upregulated the
      expression of atherosclerotic markers (VCAM-1, ICAM-1, MCP1, p22phox, and
      gp91phox). Exposure to the high dose of CS also significantly upregulated the
      miRNA-155 level in the aortic tissues of ApoE KO mice. Moreover, the expression
      level of miR-126 tended to be downregulated and that of miR-21 tended to be
      upregulated in ApoE KO mice exposed to the high dose of CS, albeit statistically
      insignificant. The results suggest that CS induces atherosclerosis through
      increased vascular inflammation and NADPH oxidase expression and also emphasize
      the importance of miRNAs in the pathogenesis of CS-induced atherosclerosis. Our
      findings provide evidence for miRNAs as potential mediators of inflammation and
      atherosclerosis induced by CS.

PMID- 29642386
TI  - Hedgehog Signals Mediate Anti-Cancer Drug Resistance in Three-Dimensional Primary
      Colorectal Cancer Organoid Culture.
AB  - Colorectal cancer is one of the most common causes of cancer death worldwide. In
      patients with metastatic colorectal cancer, combination treatment with several
      anti-cancer drugs is employed and improves overall survival in some patients.
      Nevertheless, most patients with metastatic disease are not cured owing to the
      drug resistance. Cancer stem cells are known to regulate resistance to
      chemotherapy. In the previous study, we established a novel three-dimensional
      organoid culture model from tumor colorectal tissues of human patients using an
      air-liquid interface (ALI) method, which contained numerous cancer stem cells and
      showed resistance to 5-fluorouracil (5-FU) and Irinotecan. Here, we investigate
      which inhibitor for stem cell-related signal improves the sensitivity for anti
      cancer drug treatment in tumor ALI organoids. Treatment with Hedgehog signal
      inhibitors (AY9944, GANT61) decreases the cell viability of organoids compared
      with Notch (YO-01027, DAPT) and Wnt (WAV939, Wnt-C59) signal inhibitors.
      Combination treatment of AY9944 or GANT61 with 5-FU, Irinotecan or Oxaliplatin
      decreases the cell viability of tumor organoids compared with each anti-cancer
      drug alone treatment. Treatment with AY9944 or GANT61 inhibits expression of stem
      cell markers c-Myc, CD44 and Nanog, likely through the decrease of their
      transcription factor, GLI-1 expression. Combination treatment of AY9944 or GANT61
      with 5-FU or Irinotecan also prevents colony formation of colorectal cancer cell
      lines HCT116 and SW480. These findings suggest that Hedgehog signals mediate anti
      cancer drug resistance in colorectal tumor patient-derived ALI organoids and that
      the inhibitors are useful as a combinational therapeutic strategy against
      colorectal cancer.

PMID- 29642387
TI  - A Beneficial Role of Rooibos in Diabetes Mellitus: A Systematic Review and Meta
      Analysis.
AB  - In a rapid increase in cases of diabetes mellitus worldwide, there has been
      interested in the use of plant-derived polyphenols as nutraceuticals to prevent
      the onset and progression of diabetes mellitus and its associated complications.
      Aspalathus linearis, commonly known as rooibos, is a rich source of uncommon
      glycosylated plant polyphenols with various critical health-promoting properties,
      including the prevention and treatment of diabetes mellitus (DM). This study
      aimed to examine these effects by meta-analyzing the current evidence in diabetic
      rodent models. Peer-reviewed studies written in English from two databases,
      PubMed and Embase, were searched up to 28 February 2018. Studies reporting blood
      glucose levels in diabetic rodents with and without receiving rooibos extracts or
      their major phenolic compounds are included. Twelve studies enrolling 88 diabetic
      rodents treated with rooibos extracts or their polyphenols and 85 diabetic
      control males reported blood glucose levels. The pooled effect size was -0.89
      (95% CI: -1.44 to -0.35) with a substantial heterogeneity (I2 = 67.0%). This
      effect was likely to be modified by type of rooibos extracts and their
      polyphenols and treatment period. Blood glucose levels were significantly lower
      in diabetic rodent models treated with the phenolic compound rich in rooibos
      extracts, PPAG.

PMID- 29642389
TI  - Soil Water Measurement Using Actively Heated Fiber Optics at Field Scale.
AB  - Several studies have demonstrated the potential of actively heated fiber optics
      (AHFO) to measure soil water content (SWC) at high spatial and temporal
      resolutions. This study tested the feasibility of the AHFO technique to measure
      soil water in the surface soil of a crop grown field over a growing season using
      an in-situ calibration approach. Heat pulses of five minutes duration were
      applied at a rate of 7.28 W m-1 along eighteen fiber optic cable transects
      installed at three depths (0.05, 0.10 and 0.20 m) at six-hour intervals.
      Cumulative temperature increase (Tcum) during heat pulses was calculated at
      locations along the cable. While predicting commercial sensor measurements, the
      AHFO showed root mean square errors (RMSE) of 2.8, 3.7 and 3.7% for 0.05, 0.10
      and 0.20 m depths, respectively. Further, the coefficients of determination (R2)
      for depth specific relationships were 0.87 (0.05 m depth), 0.46 (0.10 m depth),
      0.86 (0.20 m depth) and 0.66 (all depths combined). This study showed a great
      potential of the AHFO technique to measure soil water at high spatial resolutions
      (<1 m) and to monitor soil water dynamics of surface soil in a crop grown field
      over a cropping season with a reasonable compromise between accuracy and
      practicality.

PMID- 29642388
TI  - Oligodendroglioma Cells Lack Glutamine Synthetase and Are Auxotrophic for
      Glutamine, but Do not Depend on Glutamine Anaplerosis for Growth.
AB  - In cells derived from several types of cancer, a transcriptional program drives
      high consumption of glutamine (Gln), which is used for anaplerosis, leading to a
      metabolic addiction for the amino acid. Low or absent expression of Glutamine
      Synthetase (GS), the only enzyme that catalyzes de novo Gln synthesis, has been
      considered a marker of Gln-addicted cancers. In this study, two human cell lines
      derived from brain tumors with oligodendroglioma features, HOG and Hs683, have
      been shown to be GS-negative. Viability of both lines depends from extracellular
      Gln with EC50 of 0.175 +/- 0.056 mM (Hs683) and 0.086 +/- 0.043 mM (HOG), thus
      suggesting that small amounts of extracellular Gln are sufficient for OD cell
      growth. Gln starvation does not significantly affect the cell content of
      anaplerotic substrates, which, consistently, are not able to rescue cell growth,
      but causes hindrance of the Wnt/beta-catenin pathway and protein synthesis
      attenuation, which is mitigated by transient GS expression. Gln transport
      inhibitors cause partial depletion of intracellular Gln and cell growth
      inhibition, but do not lower cell viability. Therefore, GS-negative human
      oligodendroglioma cells are Gln-auxotrophic but do not use the amino acid for
      anaplerosis and, hence, are not Gln addicted, exhibiting only limited Gln
      requirements for survival and growth.

PMID- 29642390
TI  - Low Levels of Knowledge, Attitudes and Preventive Practices on Leptospirosis
      among a Rural Community in Hulu Langat District, Selangor, Malaysia.
AB  - Little is known on the knowledge, attitudes and preventive practices (KAP) of
      leptospirosis worldwide. This study embarked on assessing the KAP of
      leptospirosis among rural communities in Malaysia. A total of 444 participants
      (223 male; 221 female) aged between 18 and 81 years old were surveyed by using a
      self-administered questionnaire. A majority of participants had poor knowledge
      level (57.0%), unacceptable attitudes (90.3%) and unacceptable preventive
      practices (69.1%) on leptospirosis, and only 29.7% knew "rat-urine disease" as
      leptospirosis. Only 34.2% of the participants knew the bacteria could enter via
      wound lesions. Ethnicity and income were strongly associated with knowledge level
      and preventive practices, respectively (p-values < 0.05). As for attitudes,
      ethnicity, income and education type were significantly associated (p-values <
      0.05). Only 36.5% of the participants were willing to see a doctor and did not
      mind if their house or surrounding area is dirty (59.7%). Surprisingly, only
      32.9% had used rubber boots during floods. By logistic regression analysis,
      ethnicity was the only significant predictor for both knowledge level (an odds
      ratio (AOR) = 0.39, 95% confidence interval (CI) = 0.222-0.680) and preventive
      practices (AOR = 1.81, 95% CI = 1.204-2.734). Ethnicity (AOR = 0.40, 95% CI =
      0.239-0.665), income (AOR = 1.58, 95% CI = 1.041-2.385) and education type (AOR =
      3.69, 95% CI = 1.237-10.986) were strong predictors for attitudes. Among the KAP
      variables, attitude (AOR = 4.357, 95% CI = 2.613-7.264) was the only predictor
      for the preventive practices by logistic regression analysis. The KAP elements on
      leptospirosis are still lacking and poor health seeking behavior and attitudes
      are of our utmost concern. Thus, effective strategies should be planned to impart
      knowledge, and develop proactive approaches and good preventive modules on
      leptospirosis to this leptospirosis-prone community.

PMID- 29642391
TI  - Smart City Pilot Projects Using LoRa and IEEE802.15.4 Technologies.
AB  - Information and Communication Technologies (ICTs), through wireless
      communications and the Internet of Things (IoT) paradigm, are the enabling keys
      for transforming traditional cities into smart cities, since they provide the
      core infrastructure behind public utilities and services. However, to be
      effective, IoT-based services could require different technologies and network
      topologies, even when addressing the same urban scenario. In this paper, we
      highlight this aspect and present two smart city testbeds developed in Italy. The
      first one concerns a smart infrastructure for public lighting and relies on a
      heterogeneous network using the IEEE 802.15.4 short-range communication
      technology, whereas the second one addresses smart-building applications and is
      based on the LoRa low-rate, long-range communication technology. The smart
      lighting scenario is discussed providing the technical details and the economic
      benefits of a large-scale (around 3000 light poles) flexible and modular
      implementation of a public lighting infrastructure, while the smart-building
      testbed is investigated, through measurement campaigns and simulations, assessing
      the coverage and the performance of the LoRa technology in a real urban scenario.
      Results show that a proper parameter setting is needed to cover large urban areas
      while maintaining the airtime sufficiently low to keep packet losses at
      satisfactory levels.

PMID- 29642392
TI  - Optimization Strategies for Responsivity Control of Microgel Assisted Lab-On
      Fiber Optrodes.
AB  - Integrating multi-responsive polymers such as microgels onto optical fiber tips,
      in a controlled fashion, enables unprecedented functionalities to Lab-on-fiber
      optrodes. The creation of a uniform microgel monolayer with a specific coverage
      factor is crucial for enhancing the probes responsivity to a pre-defined target
      parameter. Here we report a reliable fabrication strategy, based on the dip
      coating technique, for the controlled realization of microgel monolayer onto
      unconventional substrates, such as the optical fiber tip. The latter was
      previously covered by a plasmonic nanostructure to make it sensitive to
      superficial environment changes. Microgels have been prepared using specific
      Poly(N-isopropylacrylamide)-based monomers that enable bulky size changes in
      response to both temperature and pH variations. The formation of the microgel
      monolayer is efficiently controlled through the selection of suitable operating
      pH, temperature and concentration of particle dispersions used during the dipping
      procedure. The effect of each parameter has been evaluated, and the validity of
      our procedure is confirmed by means of both morphological and optical
      characterizations. We demonstrate that when the coverage factor exceeds 90%, the
      probe responsivity to microgels swelling/collapsing is significantly improved.
      Our study opens new paradigms for the development of engineered microgels
      assisted Lab-on-Fiber probes for biochemical applications.

PMID- 29642393
TI  - Ancient DNA from Giant Panda (Ailuropoda melanoleuca) of South-Western China
      Reveals Genetic Diversity Loss during the Holocene.
AB  - The giant panda was widely distributed in China and south-eastern Asia during the
      middle to late Pleistocene, prior to its habitat becoming rapidly reduced in the
      Holocene. While conservation reserves have been established and population
      numbers of the giant panda have recently increased, the interpretation of its
      genetic diversity remains controversial. Previous analyses, surprisingly, have
      indicated relatively high levels of genetic diversity raising issues concerning
      the efficiency and usefulness of reintroducing individuals from captive
      populations. However, due to a lack of DNA data from fossil specimens, it is
      unknown whether genetic diversity was even higher prior to the most recent
      population decline. We amplified complete cytb and 12s rRNA, partial 16s rRNA and
      ND1, and control region sequences from the mitochondrial genomes of two Holocene
      panda specimens. We estimated genetic diversity and population demography by
      analyzing the ancient mitochondrial DNA sequences alongside those from modern
      giant pandas, as well as from other members of the bear family (Ursidae).
      Phylogenetic analyses show that one of the ancient haplotypes is sister to all
      sampled modern pandas and the second ancient individual is nested among the
      modern haplotypes, suggesting that genetic diversity may indeed have been higher
      earlier during the Holocene. Bayesian skyline plot analysis supports this view
      and indicates a slight decline in female effective population size starting
      around 6000 years B.P., followed by a recovery around 2000 years ago. Therefore,
      while the genetic diversity of the giant panda has been affected by recent
      habitat contraction, it still harbors substantial genetic diversity. Moreover,
      while its still low population numbers require continued conservation efforts,
      there seem to be no immediate threats from the perspective of genetic
      evolutionary potential.

PMID- 29642395
TI  - Retrieval of Winter Wheat Leaf Area Index from Chinese GF-1 Satellite Data Using
      the PROSAIL Model.
AB  - Leaf area index (LAI) is one of the key biophysical parameters in crop structure.
      The accurate quantitative estimation of crop LAI is essential to verify crop
      growth and health. The PROSAIL radiative transfer model (RTM) is one of the most
      established methods for estimating crop LAI. In this study, a look-up table (LUT)
      based on the PROSAIL RTM was first used to estimate winter wheat LAI from GF-1
      data, which accounted for some available prior knowledge relating to the
      distribution of winter wheat characteristics. Next, the effects of 15 LAI-LUT
      strategies with reflectance bands and 10 LAI-LUT strategies with vegetation
      indexes on the accuracy of the winter wheat LAI retrieval with different
      phenological stages were evaluated against in situ LAI measurements. The results
      showed that the LUT strategies of LAI-GNDVI were optimal and had the highest
      accuracy with a root mean squared error (RMSE) value of 0.34, and a coefficient
      of determination (R2) of 0.61 during the elongation stages, and the LUT
      strategies of LAI-Green were optimal with a RMSE of 0.74, and R2 of 0.20 during
      the grain-filling stages. The results demonstrated that the PROSAIL RTM had great
      potential in winter wheat LAI inversion with GF-1 satellite data and the
      performance could be improved by selecting the appropriate LUT inversion
      strategies in different growth periods.

PMID- 29642394
TI  - Neuroprotective Effects of Platonin, a Therapeutic Immunomodulating Medicine, on
      Traumatic Brain Injury in Mice after Controlled Cortical Impact.
AB  - Traumatic brain injury (TBI) is one of the leading causes of mortality worldwide
      and leads to persistent cognitive, sensory, motor dysfunction, and emotional
      disorders. TBI-caused primary injury results in structural damage to brain
      tissues. Following the primary injury, secondary injuries which are accompanied
      by neuroinflammation, microglial activation, and additional cell death
      subsequently occur. Platonin, a cyanine photosensitizing dye, has been used to
      treat trauma, ulcers, and some types of acute inflammation. In the present study,
      the neuroprotective effects of platonin against TBI were explored in a controlled
      cortical impact (CCI) injury model in mice. Treatment with platonin (200 ug/kg)
      significantly reduced the neurological severity score, general locomotor
      activity, and anxiety-related behavior, and improved the rotarod performance of
      CCI-injured mice. In addition, platonin reduced lesion volumes, the expression of
      cleaved caspase-3, and microglial activation in TBI-insulted brains. Platonin
      also suppressed messenger (m)RNA levels of caspase-3, caspase-1, cyclooxygenase
      2, tumor necrosis factor-alpha, interleukin-6, and interleukin-1beta. On the
      other hand, free radical production after TBI was obviously attenuated in
      platonin-treated mice. Treatment with platonin exhibited prominent
      neuroprotective properties against TBI in a CCI mouse model through its anti
      inflammatory, anti-apoptotic, and anti-free radical capabilities. This evidence
      collectively indicates that platonin may be a potential therapeutic medicine for
      use with TBIs.

PMID- 29642396
TI  - Collision Detection for Underwater ROV Manipulator Systems.
AB  - Work-class ROVs equipped with robotic manipulators are extensively used for
      subsea intervention operations. Manipulators are teleoperated by human pilots
      relying on visual feedback from the worksite. Operating in a remote environment,
      with limited pilot perception and poor visibility, manipulator collisions which
      may cause significant damage are likely to happen. This paper presents a real
      time collision detection algorithm for marine robotic manipulation. The proposed
      collision detection mechanism is developed, integrated into a commercial ROV
      manipulator control system, and successfully evaluated in simulations and
      experimental setup using a real industry standard underwater manipulator. The
      presented collision sensing solution has a potential to be a useful pilot
      assisting tool that can reduce the task load, operational time, and costs of
      subsea inspection, repair, and maintenance operations.

PMID- 29642397
TI  - Energy-Efficient Data Collection Method for Sensor Networks by Integrating
      Asymmetric Communication and Wake-Up Radio.
AB  - In large-scale wireless sensor networks (WSNs), nodes close to sink nodes consume
      energy more quickly than other nodes due to packet forwarding. A mobile sink is a
      good solution to this issue, although it causes two new problems to nodes: (i)
      overhead of updating routing information; and (ii) increased operating time due
      to aperiodic query. To solve these problems, this paper proposes an energy
      efficient data collection method, Sink-based Centralized transmission Scheduling
      (SC-Sched), by integrating asymmetric communication and wake-up radio.
      Specifically, each node is equipped with a low-power wake-up receiver. The sink
      node determines transmission scheduling, and transmits a wake-up message using a
      large transmission power, directly activating a pair of nodes simultaneously
      which will communicate with a normal transmission power. This paper further
      investigates how to deal with frame loss caused by fading and how to mitigate the
      impact of the wake-up latency of communication modules. Simulation evaluations
      confirm that using multiple channels effectively reduces data collection time and
      SC-Sched works well with a mobile sink. Compared with the conventional duty
      cycling method, SC-Sched greatly reduces total energy consumption and improves
      the network lifetime by 7.47 times in a WSN with 4 data collection points and 300
      sensor nodes.

PMID- 29642398
TI  - Novel Nanoparticulate and Ionic Titanium Antigens for Hypersensitivity Testing.
AB  - Titanium is used in a wide variety of materials ranging from medical devices to
      materials used in everyday life. Adverse biological reactions that could occur in
      patients, consumers, and workers should be monitored and prevented. There is a
      lack of available agents to test and predict titanium-related hypersensitivity.
      The aim of this study was to develop two bioavailable titanium substances in
      ionic and nanoparticulate form to serve as antigens for hypersensitivity testing
      in vitro. Peripheral blood mononuclear cells from 20 test subjects were
      stimulated with the antigens and secretion of monocytic and lymphatic cytokines
      and chemokines were measured by a multiplex bead assay. Lymphocyte stimulation
      indices were also determined in a subset of test subjects by measuring CD69 and
      HLA-DR expression by flow cytometry. Cytokine profiling revealed that both
      antigens increased production of typical monocyte and macrophage secreted
      cytokines after 24 h, with significant increases in IL-1beta, IL-7, IL-10, IL-12,
      IL-2R, IL-6, GM-CSF, TNF-alpha, IL-1RA, MIP-1alpha, MIP-1beta, IFN-alpha, and IL
      15. Lymphatic cytokines and chemokines were not significantly induced by
      activation. After seven days of stimulation, ionic-Ti (2.5 MUg/mL) caused
      proliferation (stimulation index > 2) of CD4+ cells and CD8+ cells in all persons
      tested (N = 6), while titanium dioxide nanoparticles (50 MUg/mL) only caused
      significant proliferation of CD4+ cells. Our preliminary results show that the
      experimental titanium antigens, especially the ionic form, induce a general
      inflammatory response in vitro. A relevant cohort of test subjects is required to
      further elucidate their potential for predictive hypersensitivity testing.

PMID- 29642399
TI  - Antibacterial Activity of Emulsified Pomelo (Citrus grandis Osbeck) Peel Oil and
      Water-Soluble Chitosan on Staphylococcus aureus and Escherichia coli.
AB  - This study utilized pomelo steam distillation to isolate pomelo peel essential
      oil. The constituents were then analyzed through gas chromatography-mass
      spectrometry (GC-MS), and the antibacterial activity of the essential oil
      emulsions at different homogenizer speed conditions and concentrations of water
      soluble chitosan (degree of acetylation, DA = 54.8%) against S. aureus and E.
      coli was examined. Analysis of the essential oil composition identified a total
      of 33 compounds with the main constituent, limonene accounting for 87.5% (940.07
      mg/g) of the total. The pomelo peel oil was emulsified through homogenization at
      24,000 rpm, resulting in a minimal inhibitory concentration (MIC) for E. coli
      that was 1.9 times lower than that of the essential oil without homogenization.
      In addition, a mixture of 0.4% essential oil emulsion and 0.03% water-soluble
      chitosan had the strongest synergetic antibacterial effect on S. aureus and E.
      coli at pH 7.4. In comparison with chitosan alone, the MIC value of this mixture
      was significantly 2.4 and 2.5 times lower. Hence, this study suggests using a
      mixture of emulsified pomelo peel oil and water-soluble chitosan to develop a
      novel natural food preservative, and that the processability of food, as well as
      the economic value of the byproducts of the Taiwan Matou pomelo and chitosan,
      could be increased.

PMID- 29642400
TI  - Iron and the Breastfed Infant.
AB  - The first 6 months of life is a crucial time in meeting iron needs. The purpose
      of this review is to examine iron in mother's milk and whether or not it meets
      the physiological needs of the growing infant. Key issues include iron content
      and iron transport from the mammary gland as well as when and what foods should
      be added to the solely breastfed infant. We examine these topics in light of new
      molecular biology findings in the mammary gland.

PMID- 29642401
TI  - Oral Vaccination with a DNA Vaccine Encoding Capsid Protein of Duck Tembusu Virus
      Induces Protection Immunity.
AB  - The emergence of duck tembusu virus (DTMUV), a new member of the Flavivirus
      genus, has caused great economical loss in the poultry industry in China. Since
      the outbreak and spread of DTMUV is hard to control in a clinical setting, an
      efficient and low-cost oral delivery DNA vaccine SL7207 (pVAX1-C) based on the
      capsid protein of DTMUV was developed and evaluated in this study. The antigen
      capsid protein was expressed from the DNA vaccine SL7207 (pVAX1-C), both in vitro
      and in vivo. The humoral and cellular immune responses in vivo were observed
      after oral immunization with the SL7207 (pVAX1-C) DNA vaccine. High titers of the
      specific antibody against the capsid protein and the neutralizing antibody
      against the DTMUV virus were both detected after inoculation. The ducks were
      efficiently protected from lethal DTMUV exposure by the SL7207 (pVAX1-C) vaccine
      in this experiment. Taken together, we demonstrated that the capsid protein of
      DTMUV possesses a strong immunogenicity against the DTMUV infection. Moreover, an
      oral delivery of the DNA vaccine SL7207 (pVAX1-C) utilizing Salmonella SL7207 was
      an efficient way to protect the ducks against DTMUV infection and provides an
      economic and fast vaccine delivery strategy for a large scale clinical use.

PMID- 29642402
TI  - Therapeutic Use of Stem Cells for Myocardial Infarction.
AB  - Myocardial infarction is a leading cause of morbidity and mortality worldwide.
      Although medical and surgical treatments can significantly improve patient
      outcomes, no treatment currently available is able to generate new contractile
      tissue or reverse ischemic myocardium. Driven by the recent/novel understanding
      that regenerative processes do exist in the myocardium-tissue previously thought
      not to possess regenerative properties-the use of stem cells has emerged as a
      promising therapeutic approach with high expectations. The literature describes
      the use of cells from various sources, categorizing them as either embryonic,
      induced pluripotent, or adult/tissue stem cells (mesenchymal, hematopoietic,
      skeletal myoblasts, cardiac stem cells). Many publications show the successful
      use of these cells to regenerate damaged myocardium in both animal and human
      models; however, more studies are needed to directly compare cells of various
      origins in efforts to draw conclusions on the ideal source. Although numerous
      challenges exist in this developing area of research and clinical practice,
      prospects are encouraging. The following aims to provide a concise review
      outlining the different types of stem cells used in patients after myocardial
      infarction.

PMID- 29642403
TI  - Cebpd Is Essential for Gamma-Tocotrienol Mediated Protection against Radiation
      Induced Hematopoietic and Intestinal Injury.
AB  - Gamma-tocotrienol (GT3) confers protection against ionizing radiation (IR)
      induced injury. However, the molecular targets that underlie the protective
      functions of GT3 are not yet known. We have reported that mice lacking CCAAT
      enhancer binding protein delta (Cebpd-/-) display increased mortality to IR due
      to injury to the hematopoietic and intestinal tissues and that Cebpd protects
      from IR-induced oxidative stress and cell death. The purpose of this study was to
      investigate whether Cebpd mediates the radio protective functions of GT3. We
      found that GT3-treated Cebpd-/- mice showed partial recovery of white blood cells
      compared to GT3-treated Cebpd+/+ mice at 2 weeks post-IR. GT3-treated Cebpd-/-
      mice showed an increased loss of intestinal crypt colonies, which correlated with
      increased expression of inflammatory cytokines and chemokines, increased levels
      of oxidized glutathione (GSSG), S-nitrosoglutathione (GSNO) and 3-nitrotyrosine
      (3-NT) after exposure to IR compared to GT3-treated Cebpd+/+ mice. Cebpd is
      induced by IR as well as a combination of IR and GT3 in the intestine. Studies
      have shown that granulocyte-colony stimulating factor (G-CSF), mediates the
      radioprotective functions of GT3. Interestingly, we found that IR alone as well
      as the combination of IR and GT3 caused robust augmentation of plasma G-CSF in
      both Cebpd+/+ and Cebpd-/- mice. These results identify a novel role for Cebpd in
      GT3-mediated protection against IR-induced injury, in part via modulation of IR
      induced inflammation and oxidative/nitrosative stress, which is independent of G
      CSF.

PMID- 29642404
TI  - Improved Optical and Morphological Properties of Vinyl-Substituted Hybrid Silica
      Materials Incorporating a Zn-Metalloporphyrin.
AB  - This work is focused on a novel class of hybrid materials exhibiting enhanced
      optical properties and high surface areas that combine the morphology offered by
      the vinyl substituted silica host, and the excellent absorption and emission
      properties of 5,10,15,20-tetrakis(N-methyl-4-pyridyl)porphyrin-Zn(II)
      tetrachloride as a water soluble guest molecule. In order to optimize the
      synthesis procedure and the performance of the immobilized porphyrin, silica
      precursor mixtures of different compositions were used. To achieve the
      requirements regarding the hydrophobicity and the porous structure of the gels
      for the successful incorporation of porphyrin, the content of
      vinyltriacetoxysilane was systematically changed and thoroughly investigated.
      Substitution of the silica gels with organic groups is a viable way to provide
      new properties to the support. An exhaustive characterization of the synthesized
      silica samples was realised by complementary physicochemical methods, such as
      infrared spectroscopy (FT-IR), absorption spectroscopy (UV-Vis) and
      photoluminescence, nuclear magnetic resonance spectroscopy (29Si-MAS-NMR)
      transmission and scanning electron microscopy (TEM and SEM), nitrogen absorption
      (BET), contact angle (CA), small angle X ray and neutron scattering (SAXS and
      SANS). All hybrids showed an increase in emission intensity in the wide region
      from 575 to 725 nm (Q bands) in comparison with bare porphyrin. By simply tuning
      the vinyltriacetoxysilane content, the hydrophilic/hydrophobic profile of the
      hybrid materials was changed, while maintaining a high surface area. Good control
      of hydrophobicity is important to enhance properties such as dispersion,
      stability behaviour, and resistance to water, in order to achieve highly
      dispersible systems in water for biomedical applications.

PMID- 29642405
TI  - Transcriptome Analysis of Acute Phase Liver Graft Injury in Liver
      Transplantation.
AB  - BACKGROUND: Liver transplantation remains the treatment of choice for a selected
      group of hepatocellular carcinoma (HCC) patients. However, the long-term benefit
      is greatly hampered by post-transplant HCC recurrence. Our previous studies have
      identified liver graft injury as an acute phase event leading to post-transplant
      tumor recurrence. METHODS: To re-examine this acute phase event at the molecular
      level and in an unbiased way, RNA sequencing (RNA-Seq) was performed on liver
      graft biopsies obtained from the transplant recipients two hours after portal
      vein reperfusion with an aim to capture frequently altered pathways that account
      for post-transplant tumor recurrence. Liver grafts from recurrent recipients (n =
      6) were sequenced and compared with those from recipients without recurrence (n =
      5). RESULTS: RNA expression profiles comparison pointed to several frequently
      altered pathways, among which pathways related to cell adhesion molecules were
      the most involved. Subsequent validation using quantitative polymerase chain
      reaction confirmed the differential involvement of two cell adhesion molecules
      HFE (hemochromatosis) and CD274 and their related molecules in the acute phase
      event. CONCLUSION: This whole transcriptome strategy unravels the molecular
      landscape of liver graft gene expression alterations, which can identify key
      pathways and genes that are involved in acute phase liver graft injury that may
      lead to post-transplant tumor recurrence.

PMID- 29642406
TI  - Fucoidan Rescues p-Cresol-Induced Cellular Senescence in Mesenchymal Stem Cells
      via FAK-Akt-TWIST Axis.
AB  - Mesenchymal stem cells (MSCs) are a source for cell-based therapy. Although MSCs
      have the potential for tissue regeneration, their therapeutic efficacy is
      restricted by the uremic toxin, p-cresol, in chronic kidney disease (CKD). To
      address this issue, we investigated the effect of fucoidan, a marine sulfated
      polysaccharide, on cellular senescence in MSCs. After p-cresol exposure, MSC
      senescence was induced, as indicated by an increase in cell size and a decrease
      in proliferation capacity. Treatment of senescent MSCs with fucoidan
      significantly reversed this cellular senescence via regulation of SMP30 and p21,
      and increased proliferation through the regulation of cell cycle-associated
      proteins (CDK2, CDK4, cyclin D1, and cyclin E). These effects were dependent on
      FAK-Akt-TWIST signal transduction. In particular, fucoidan promoted the
      expression of cellular prion protein (PrPC), which resulted in the maintenance of
      cell expansion capacity in p-cresol-induced senescent MSCs. This protective
      effect of fucoidan on senescence-mediated inhibition of proliferation was
      dependent on the TWIST-PrPC axis. In summary, this study shows that fucoidan
      protects against p-cresol-induced cellular senescence in MSCs through activation
      of the FAK-Akt-TWIST pathway and suggests that fucoidan could be used in
      conjunction with functional MSC-based therapies in the treatment of CKD.

PMID- 29642407
TI  - Load-Bearing Capacity and Retention of Newly Developed Micro-Locking Implant
      Prosthetic System: An In Vitro Pilot Study.
AB  - The aim of this study was to introduce the newly developed micro-locking implant
      prosthetic system and to evaluate the resulting its characteristics. To evaluate
      load-bearing capacity, 25 implants were divided into five groups: external
      hexagon connection (EH), internal-octagon connection (IO), internal-hexagon
      connection (IH), one-body implant (OB), micro-locking implant system (ML). The
      maximum compressive load was measured using a universal testing machine (UTM)
      according to the ISO 14801. Retention was evaluated in two experiments: (1) a
      tensile test of the structure modifications of the components (attachment and
      implant) and (2) a tensile test after cyclic loading (total 5,000,000 cycles, 100
      N, 2 Hz). The load-bearing capacity of the ML group was not significantly
      different from the other groups (p > 0.05). The number of balls in the attachment
      and the presence of a hexagonal receptacle did not show a significant correlation
      with retention (p > 0.05), but the shape of the retentive groove in the implant
      post had a statistically significant effect on retention (p < 0.05). On the other
      hand, the retention loss was observed during the initial 1,000,000 cycles, but an
      overall constant retention was maintained afterward. Various preclinical studies
      on this novel micro-locking implant prosthetic system should continue so that it
      can be applied in clinical practice.

PMID- 29642408
TI  - Mucormycosis: Battle with the Deadly Enemy over a Five-Year Period in India.
AB  - Mucormycosis is an emerging opportunistic fungal infection. Increasing
      immunocompromization, widespread use of antibacterial and antifungal agents (such
      as voriconazole prophylaxis), carcinomas, transplantation and lifestyle diseases
      such as diabetes are the main contributors to this situation. The predominant
      clinical manifestations of mucormycosis vary from host to host, with rhino
      orbital-cerebral, pulmonary, cutaneous, and gastrointestinal infections being the
      most common. In India, the prevalence of mucormycosis is approximately 0.14
      cases/1000 population, which is about 70 times the worldwide-estimated rate for
      mucormycosis. The present study was undertaken over a period of five years
      (January 2009-December 2014) to determine the prevalence of mucormycosis. The
      samples suspected of mucormycosis were examined by direct KOH wet mount and
      cultured on Sabouraud's dextrose agar without actidione and on blood agar as per
      standard mycological techniques. Histopathological correlation was done for most
      of the cases. Antifungal susceptibility testing was performed by the EUCAST
      reference method. We identified a total of 82 cases of mucormycosis out of a
      total of 6365 samples received for mycological culture and examination during the
      said time period. Out of these, 56 were male patients and 27 were females. Most
      common presentation was rhino-orbito-cerebral (37), followed by cutaneous (25),
      pulmonary (14), oral cavity involvement (4) and gastrointestinal (2). The most
      common risk factors were diabetes and intramuscular injections. The fungi
      isolated were Rhizopus arrhizus (17), Apophysomyces variabilis (12), R.
      microsporus (9), Lichtheimia ramosa (8), Saksenaea erythrospora (5),
      Syncephalastrum racemosus (4), R. homothallicus (2), Rhizomucor pusillus (1),
      Mucor irregularis (1) and A. elegans (1). The mainstay of the treatment was
      amphotericin B, along with extensive surgical debridement whenever feasible. Most
      of the patients (50) recovered, but 25 died. The rest of the patients left
      against medical advice. "Nip in the Bud" should be the mantra for
      clinicians/surgeons for a favorable prognosis. Early diagnosis, prompt
      institution of appropriate antifungal therapy, surgical debridement whenever
      necessary, knowledge of risk factors and their timely reversal is the key for
      management.

PMID- 29642410
TI  - Latent Factors Limiting the Performance of sEMG-Interfaces.
AB  - Recent advances in recording and real-time analysis of surface electromyographic
      signals (sEMG) have fostered the use of sEMG human-machine interfaces for
      controlling personal computers, prostheses of upper limbs, and exoskeletons among
      others. Despite a relatively high mean performance, sEMG-interfaces still exhibit
      strong variance in the fidelity of gesture recognition among different users.
      Here, we systematically study the latent factors determining the performance of
      sEMG-interfaces in synthetic tests and in an arcade game. We show that the degree
      of muscle cooperation and the amount of the body fatty tissue are the decisive
      factors in synthetic tests. Our data suggest that these factors can only be
      adjusted by long-term training, which promotes fine-tuning of low-level neural
      circuits driving the muscles. Short-term training has no effect on synthetic
      tests, but significantly increases the game scoring. This implies that it works
      at a higher decision-making level, not relevant for synthetic gestures. We
      propose a procedure that enables quantification of the gestures' fidelity in a
      dynamic gaming environment. For each individual subject, the approach allows
      identifying "problematic" gestures that decrease gaming performance. This
      information can be used for optimizing the training strategy and for adapting the
      signal processing algorithms to individual users, which could be a way for a
      qualitative leap in the development of future sEMG-interfaces.

PMID- 29642409
TI  - Squamous Cell Carcinoma Antigen 2 (SCCA2, SERPINB4): An Emerging Biomarker for
      Skin Inflammatory Diseases.
AB  - Squamous cell carcinoma antigens 1 and 2 (SCCA1 and 2, SERPIN B3 and B4), members
      of the ovalbumin serpin (ov-serpin)/clade B serpin family, were originally
      discovered as tumor-specific antigens and are used as tumor markers for various
      kinds of squamous cell carcinomas. Recently, our understanding of the underlying
      mechanisms of how SCCA1/2 enhance tumor growth has greatly increased. Moreover,
      it has been shown that SCCA1/2 are involved in the pathogenesis of several
      inflammatory diseases: asthma, psoriasis, and atopic dermatitis (AD). IL-22 and
      IL-17, signature cytokines of type 17 inflammation, as well as IL-4 and IL-13,
      signature cytokines of type 2 inflammation, both of which are positively
      correlated with the pathogenesis of psoriasis and allergic diseases,
      respectively, can induce expression of SCCA1/2 in airway epithelial cells and/or
      keratinocytes, leading to high expression of SCCA1/2 in these diseases. Based on
      these findings, several trials have been performed to examine the potential of
      applying SCCA1/2 to biomarkers for these diseases. The findings show that SCCA2
      is useful to aid diagnosis, estimate clinical severity and disease type, and
      assess responses to treatment in psoriasis and AD. These results suggest that
      SCCA2 has emerged as a novel biomarker for skin inflammatory diseases.

PMID- 29642411
TI  - Presence of Human Enteric Viruses, Protozoa, and Indicators of Pathogens in the
      Bagmati River, Nepal.
AB  - Quantification of waterborne pathogens in water sources is essential for alerting
      the community about health hazards. This study determined the presence of human
      enteric viruses and protozoa in the Bagmati River, Nepal, and detected fecal
      indicator bacteria (total coliforms, Escherichia coli, and Enterococcus spp.),
      human-fecal markers (human Bacteroidales and JC and BK polyomaviruses), and index
      viruses (tobacco mosaic virus and pepper mild mottle virus). During a one-year
      period between October 2015 and September 2016, a total of 18 surface water
      samples were collected periodically from three sites along the river. Using
      quantitative polymerase chain reaction, all eight types of human enteric viruses
      tested-including adenoviruses, noroviruses, and enteroviruses, were detected
      frequently at the midstream and downstream sites, with concentrations of 4.4-8.3
      log copies/L. Enteroviruses and saliviruses were the most frequently detected
      enteric viruses, which were present in 72% (13/18) of the tested samples. Giardia
      spp. were detected by fluorescence microscopy in 78% (14/18) of the samples, with
      a lower detection ratio at the upstream site. Cryptosporidium spp. were detected
      only at the midstream and downstream sites, with a positive ratio of 39% (7/18).
      The high concentrations of enteric viruses suggest that the midstream and
      downstream regions are heavily contaminated with human feces and that there are
      alarming possibilities of waterborne diseases. The concentrations of enteric
      viruses were significantly higher in the dry season than the wet season (p <
      0.05). There was a significant positive correlation between the concentrations of
      human enteric viruses and the tested indicators for the presence of pathogens
      (IPP) (p < 0.05), suggesting that these IPP can be used to estimate the presence
      of enteric viruses in the Bagmati River water.

PMID- 29642412
TI  - Signal Quality Improvement Algorithms for MEMS Gyroscope-Based Human Motion
      Analysis Systems: A Systematic Review.
AB  - Motion sensors such as MEMS gyroscopes and accelerometers are characterized by a
      small size, light weight, high sensitivity, and low cost. They are used in an
      increasing number of applications. However, they are easily influenced by
      environmental effects such as temperature change, shock, and vibration. Thus,
      signal processing is essential for minimizing errors and improving signal quality
      and system stability. The aim of this work is to investigate and present a
      systematic review of different signal error reduction algorithms that are used
      for MEMS gyroscope-based motion analysis systems for human motion analysis or
      have the potential to be used in this area. A systematic search was performed
      with the search engines/databases of the ACM Digital Library, IEEE Xplore,
      PubMed, and Scopus. Sixteen papers that focus on MEMS gyroscope-related signal
      processing and were published in journals or conference proceedings in the past
      10 years were found and fully reviewed. Seventeen algorithms were categorized
      into four main groups: Kalman-filter-based algorithms, adaptive-based algorithms,
      simple filter algorithms, and compensation-based algorithms. The algorithms were
      analyzed and presented along with their characteristics such as advantages,
      disadvantages, and time limitations. A user guide to the most suitable signal
      processing algorithms within this area is presented.

PMID- 29642413
TI  - Aqueous Phase Synthesis of CuIn Alloy Nanoparticles and Their Application for a
      CIS (CuInSe2)-Based Printable Solar Battery.
AB  - To apply CuInSe2 (CIS)-based printable solar batteries; an aqueous phase
      synthesis method of Cu-In (CI) alloy nanoparticles is studied. Metal complexes in
      the original solution are restricted to homogenized species by utilizing
      calculations. For example; [(Cu2+)(ASP2-)2] [ASP: the "body (C4H5O4N)" of
      aspartic acid (C4H7O4N)] is predominant in the pH 6-13 region (CASP/CCu > 6);
      while In complexes can be restricted to [(In3+)(OH-)(EDTA4-)] (pH 10-12;
      CEDTA/CIn = 2) and/or [(In3+)(ASP2-)2] (pH 7-9; CASP/CIn = 5). These results
      indicate that the added amount of complex reagents should be determined by
      calculations and not the stoichiometric ratio. The reduction potential of
      homogenized metal complex is measured by cyclic voltammetry (CV) measurements and
      evaluated by Nernst's equation using the overall stability constants. CuIn alloy
      nanoparticles with a small amount of byproduct (In nanoparticles) are
      successfully synthesized. The CI precursor films are spin-coated onto the
      substrate using a 2-propanol dispersion. Then the films are converted into CIS
      solar cells; which show a maximum conversion efficiency of 2.30%. The
      relationship between the open circuit potential; short circuit current density;
      and fill factor indicate that smoothing of the CIS films and improving the
      crystallinity and thickness increase the solar cell conversion efficiency.

PMID- 29642414
TI  - Proteomic Profiles of Adipose and Liver Tissues from an Animal Model of Metabolic
      Syndrome Fed Purple Vegetables.
AB  - Metabolic Syndrome (MetS) is a complex disorder that predisposes an individual to
      Cardiovascular Diseases and type 2 Diabetes Mellitus. Proteomics and
      bioinformatics have proven to be an effective tool to study complex diseases and
      mechanisms of action of nutrients. We previously showed that substitution of the
      majority of carbohydrate in a high fat diet by purple potatoes (PP) or purple
      carrots (PC) improved insulin sensitivity and hypertension in an animal model of
      MetS (obese Zucker rats) compared to a control sucrose-rich diet. In the current
      study, we used TMT 10plex mass tag combined with LC-MS/MS technique to study
      proteomic modulation in the liver (n = 3 samples/diet) and adipose tissue (n = 3
      samples/diet) of high fat diet-fed rats with or without substituting sucrose for
      purple vegetables, followed by functional enrichment analysis, in an attempt to
      elucidate potential molecular mechanisms responsible for the phenotypic changes
      seen with purple vegetable feeding. Protein folding, lipid metabolism and
      cholesterol efflux were identified as the main modulated biological themes in
      adipose tissue, whereas lipid metabolism, carbohydrate metabolism and oxidative
      stress were the main modulated themes in liver. We propose that enhanced protein
      folding, increased cholesterol efflux and higher free fatty acid (FFA) re
      esterification are mechanisms by which PP and PC positively modulate MetS
      pathologies in adipose tissue, whereas, decreased de novo lipogenesis, oxidative
      stress and FFA uptake, are responsible for the beneficial effects in liver. In
      conclusion, we provide molecular evidence for the reported metabolic health
      benefits of purple carrots and potatoes and validate that these vegetables are
      good choices to replace other simple carbohydrate sources for better metabolic
      health.

PMID- 29642415
TI  - Rothmund-Thomson Syndrome: Insights from New Patients on the Genetic Variability
      Underpinning Clinical Presentation and Cancer Outcome.
AB  - Biallelic mutations in RECQL4 gene, a caretaker of the genome, cause Rothmund
      Thomson type-II syndrome (RTS-II) and confer increased cancer risk if they damage
      the helicase domain. We describe five families exemplifying clinical and allelic
      heterogeneity of RTS-II, and report the effect of pathogenic RECQL4 variants by
      in silico predictions and transcripts analyses. Complete phenotype of patients
      #39 and #42 whose affected siblings developed osteosarcoma correlates with their
      c.[1048_1049del], c.[1878+32_1878+55del] and c.[1568G>C;1573delT],
      c.[3021_3022del] variants which damage the helicase domain. Literature survey
      highlights enrichment of these variants affecting the helicase domain in patients
      with cancer outcome raising the issue of strict oncological surveillance.
      Conversely, patients #29 and #19 have a mild phenotype and carry, respectively,
      the unreported homozygous c.3265G>T and c.3054A>G variants, both sparing the
      helicase domain. Finally, despite matching several criteria for RTS clinical
      diagnosis, patient #38 is heterozygous for c.2412_2414del; no pathogenic CNVs out
      of those evidenced by high-resolution CGH-array, emerged as contributors to her
      phenotype.

PMID- 29642416
TI  - Microenvironment Responsive Modulations in the Fatty Acid Content, Cell Surface
      Hydrophobicity, and Adhesion of Candida albicans Cells.
AB  - Considering the significance in survival and virulence, we have made an attempt
      to understand modulations in the membrane and cell wall properties of Candida
      albicans hyphae induced by temperature (37  degrees C) and neutral pH and yeast
      form cells grown under low hydrostatic pressure (LHP). Our results suggest that
      cell surface hydrophobicity (CSH) and adhesion are dynamic properties determined
      largely by the microenvironment rather than morphological forms, citing the
      significance of variation in niche specific virulence. GC-MS analysis showed that
      49 and 41 fatty acids modulated under hyphal form induced by temperature alone
      (37  degrees C) and neutral pH, respectively while that of 58 under yeast form
      cells under low hydrostatic pressure (LHP) (1800 Pa). Fatty acid and ergosterol
      data indicates that fluidity increases with increase in temperature (37  degrees
      C) and neutral pH i.e., saturated fatty acids and ergosterol decreases.
      Similarly, CSH and adhesion decrease in response to temperature (37  degrees C),
      pH 7, and LHP compared to controls, irrespective of morphological forms. In
      general, membranes were more rigid, and cell walls were more hydrophobic and
      adhesive in yeast form compared to hyphal form cells, except in case of yeast
      form cells grown under LHP. Yeast form cells grown under LHP are less hydrophobic
      and adhesive.

PMID- 29642417
TI  - Molecular Consortia-Various Structural and Synthetic Concepts for More Effective
      Therapeutics Synthesis.
AB  - The design and discovery of novel drug candidates are the initial and most
      probably the crucial steps in the drug development process. One of the tasks of
      medicinal chemistry is to produce new molecules that have a desired biological
      effect. However, even today the search for new pharmaceuticals is a very
      complicated process that is hard to rationalize. Literature provides many
      scientific reports on future prospects of design of potentially useful drugs.
      Many trends have been proposed for the design of new drugs containing different
      structures (dimers, heterodimers, heteromers, adducts, associates, complexes,
      biooligomers, dendrimers, dual-, bivalent-, multifunction drugs and codrugs,
      identical or non-identical twin drugs, mixed or combo drugs, supramolecular
      particles and various nanoindividuals. Recently much attention has been paid to
      different strategies of molecular hybridization. In this paper, various molecular
      combinations were described e.g., drug-drug or drug-non-drug combinations which
      are expressed in a schematic multi-factor form called a molecular matrix,
      consisting of four factors: association mode, connection method, and the number
      of elements and linkers. One of the most popular trends is to create small-small
      molecule combinations such as different hybrids, codrugs, drug-drug conjugates
      (DDCs) and small-large molecule combinations such as antibody-drug conjugates
      (ADCs), polymer-drug conjugates (PDCs) or different prodrugs and macromolecular
      therapeutics. A review of the structural possibilities of active framework
      combinations indicates that a wide range of potentially effective novel-type
      compounds can be formed. What is particularly important is that new therapeutics
      can be obtained in fast, efficient, and selective methods using current trends in
      chemical synthesis and the design of drugs such as the "Lego" concept or rational
      green approach.

PMID- 29642418
TI  - Toxicological Investigations on the Sea Urchin Tripneustes gratilla
      (Toxopneustidae, Echinoid) from Anaho Bay (Nuku Hiva, French Polynesia): Evidence
      for the Presence of Pacific Ciguatoxins.
AB  - The sea urchin Tripneustes gratilla (Toxopneustidae, Echinoids) is a source of
      protein for many islanders in the Indo-West Pacific. It was previously reported
      to occasionally cause ciguatera-like poisoning; however, the exact nature of the
      causative agent was not confirmed. In April and July 2015, ciguatera poisonings
      were reported following the consumption of T.gratilla in Anaho Bay (Nuku Hiva
      Island, Marquesas archipelago, French Polynesia). Patient symptomatology was
      recorded and sea urchin samples were collected from Anaho Bay in July 2015 and
      November 2016. Toxicity analysis using the neuroblastoma cell-based assay (CBA
      N2a) detected the presence of ciguatoxins (CTXs) in T.gratilla samples.
      Gambierdiscus species were predominant in the benthic assemblages of Anaho Bay,
      and G.polynesiensis was highly prevalent in in vitro cultures according to qPCR
      results. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyses
      revealed that P-CTX-3B was the major ciguatoxin congener in toxic sea urchin
      samples, followed by 51-OH-P-CTX-3C, P-CTX-3C, P-CTX-4A, and P-CTX-4B. Between
      July 2015 and November 2016, the toxin content in T.gratilla decreased, but was
      consistently above the safety limit allowed for human consumption. This study
      provides evidence of CTX bioaccumulation in T.gratilla as a cause of ciguatera
      like poisoning associated with a documented symptomatology.

PMID- 29642419
TI  - Treatment of Multidrug-Resistant Leukemia Cells by Novel Artemisinin-, Egonol-,
      and Thymoquinone-Derived Hybrid Compounds.
AB  - Two major obstacles for successful cancer treatment are the toxicity of
      cytostatics and the development of drug resistance in cancer cells during
      chemotherapy. Acquired or intrinsic drug resistance is responsible for almost 90%
      of treatment failure. For this reason, there is an urgent need for new anticancer
      drugs with improved efficacy against cancer cells, and with less toxicity on
      normal cells. There are impressive examples demonstrating the success of natural
      plant compounds to fight cancer, such as Vinca alkaloids, taxanes, and
      anthracyclines. Artesunic acid (ARTA), a drug for malaria treatment, also exerts
      cytotoxic activity towards cancer cells. Multidrug resistance often results from
      drug efflux pumps (ABC-transporters) that reduce intracellular drug levels.
      Hence, it would be interesting to know, whether ARTA could overcome drug
      resistance of tumor cells, and in what way ABC-transporters are involved.
      Different derivatives showing improved features concerning cytotoxicity and
      pharmacokinetic behavior have been developed. Considering both drug sensitivity
      and resistance, we chose a sensitive and a doxorubicin-resistant leukemia cell
      line and determined the killing effect of ARTA on these cells. Molecular docking
      and doxorubicin efflux assays were performed to investigate the interaction of
      the derivatives with P-glycoprotein. Using single-cell gel electrophoresis
      (alkaline comet assay), we showed that the derivatives of ARTA induce DNA
      breakage and accordingly programmed cell death, which represents a promising
      strategy in cancer treatment. ARTA activated apoptosis in cancer cells by the
      iron-mediated generation of reactive oxygen species (ROS). In conclusion, ARTA
      derivatives may bear the potential to be further developed as anticancer drugs.

PMID- 29642421
TI  - Nano-Graphene Oxide Functionalized Bioactive Poly(lactic acid) and Poly(epsilon
      caprolactone) Nanofibrous Scaffolds.
AB  - A versatile and convenient way to produce bioactive poly(lactic acid) (PLA) and
      poly(epsilon-caprolactone) (PCL) electrospun nanofibrous scaffolds is described.
      PLA and PCL are extensively used as biocompatible scaffold materials for tissue
      engineering. Here, biobased nano graphene oxide dots (nGO) are incorporated in
      PLA or PCL electrospun scaffolds during the electrospinning process aiming to
      enhance the mechanical properties and endorse osteo-bioactivity. nGO was found to
      tightly attach to the fibers through secondary interactions. It also improved the
      electrospinnability and fiber quality. The prepared nanofibrous scaffolds
      exhibited enhanced mechanical properties, increased hydrophilicity, good
      cytocompatibility and osteo-bioactivity. Therefore, immense potential for bone
      tissue engineering applications is anticipated.

PMID- 29642422
TI  - Chemical Characterization of an Encapsulated Red Wine Powder and Its Effects on
      Neuronal Cells.
AB  - Red wine polyphenols are known for their implications for human health
      protection, although they suffer from high instability. For this reason, a red
      wine powder was prepared by freeze-drying encapsulation in maltodextrin/arabic
      gum matrix, and its composition was determined by means of high-performance
      liquid chromatography coupled quadrupole time-of-flight mass spectrometry (HPLC
      MS-QTOF). More than thirty polyphenols, including anthocyanins, flavanols,
      flavonols, phenolic acids and stilbenoids, were identified. Some of the main
      quantified polyphenols were: malvidin-3-O-glucoside, malvidin 3-O-(6"-acetyl
      glucose), petunidin-3-O-glucoside, quercetin-3-O-glucuronide, syringenin-3-O
      glucoside, epicatechin, gallic acid and syringic acid. The biological activity of
      this de-alcoholized and encapsulated red wine on human neuroblastoma SH-SY5Y
      cells was studied. The results showed that the encapsulated red wine powder has
      active redox properties, as verified by performing reactive oxygen species (ROS)
      analysis utilizing a neuronal model. This could help explain its action against
      the neurotoxicity induced by 6-hydroxydopamine (6-OHDA).

PMID- 29642420
TI  - EBNA1: Oncogenic Activity, Immune Evasion and Biochemical Functions Provide
      Targets for Novel Therapeutic Strategies against Epstein-Barr Virus- Associated
      Cancers.
AB  - The presence of the Epstein-Barr virus (EBV)-encoded nuclear antigen-1 (EBNA1)
      protein in all EBV-carrying tumours constitutes a marker that distinguishes the
      virus-associated cancer cells from normal cells and thereby offers opportunities
      for targeted therapeutic intervention. EBNA1 is essential for viral genome
      maintenance and also for controlling viral gene expression and without EBNA1, the
      virus cannot persist. EBNA1 itself has been linked to cell transformation but the
      underlying mechanism of its oncogenic activity has been unclear. However, recent
      data are starting to shed light on its growth-promoting pathways, suggesting that
      targeting EBNA1 can have a direct growth suppressing effect. In order to carry
      out its tasks, EBNA1 interacts with cellular factors and these interactions are
      potential therapeutic targets, where the aim would be to cripple the virus and
      thereby rid the tumour cells of any oncogenic activity related to the virus.
      Another strategy to target EBNA1 is to interfere with its expression. Controlling
      the rate of EBNA1 synthesis is critical for the virus to maintain a sufficient
      level to support viral functions, while at the same time, restricting expression
      is equally important to prevent the immune system from detecting and destroying
      EBNA1-positive cells. To achieve this balance EBNA1 has evolved a unique repeat
      sequence of glycines and alanines that controls its own rate of mRNA translation.
      As the underlying molecular mechanisms for how this repeat suppresses its own
      rate of synthesis in cis are starting to be better understood, new therapeutic
      strategies are emerging that aim to modulate the translation of the EBNA1 mRNA.
      If translation is induced, it could increase the amount of EBNA1-derived
      antigenic peptides that are presented to the major histocompatibility (MHC) class
      I pathway and thus, make EBV-carrying cancers better targets for the immune
      system. If translation is further suppressed, this would provide another means to
      cripple the virus.

PMID- 29642423
TI  - Colour Counts: Sunlight and Skin Type as Drivers of Vitamin D Deficiency at UK
      Latitudes.
AB  - Sunlight exposure, with resulting cutaneous synthesis, is a major source of
      vitamin D for many, while dietary intake is low in modern diets. The constitutive
      pigment in skin determines skin type, observed as white, brown, or black skin.
      The melanin pigment absorbs ultraviolet radiation (UVR) and protects underlying
      skin from damage caused by UVR. It also reduces the UVR available for vitamin D
      synthesis in the skin. It has been shown that the white-skinned population of the
      UK are able to meet their vitamin D needs with short, daily lunchtime exposures
      to sunlight. We have followed the same methodology, based on a 10-year UK all
      weather UVR climatology, observation (sun exposure, diet, vitamin D status), and
      UVR intervention studies with Fitzpatrick skin type V (brown) adults, to
      determine whether sunlight at UK latitudes could provide an adequate source of
      vitamin D for this section of the population. Results show that to meet vitamin D
      requirements, skin type V individuals in the UK need ~25 min daily sunlight at
      lunchtime, from March to September. This makes several assumptions, including
      that forearms and lower legs are exposed June-August; only exposing hands and
      face at this time is inadequate. For practical and cultural reasons, enhanced
      oral intake of vitamin D should be considered for this population.

PMID- 29642424
TI  - On-Chip Cell Staining and Counting Platform for the Rapid Detection of Blood
      Cells in Cerebrospinal Fluid.
AB  - Counting blood cells in cerebrospinal fluid (CSF) is indispensable for diagnosing
      several pathological conditions in the central nervous system, such as
      meningitis, even though collecting CSF samples is invasive. Cell counting
      methods, such as hemocytometer chambers and flow cytometers, have been used for
      CSF cell counting, but they often lack the sensitivity to detect low blood cell
      numbers. They also depend on off-chip, manual sample preparation or require
      bulky, costly equipment, thereby limiting their clinical utility. Here, we
      present a portable cell counting platform for simple, rapid CSF cell counting
      that integrates a microfluidic cell counting chamber with a miniaturized
      microscope. The microfluidic chamber is designed not only to be a reagent
      container for on-chip cell staining but also to have a large control volume for
      accurate cell counting. The proposed microscope miniaturizes both bright-field
      and fluorescence microscopy with a simple optical setup and a custom cell
      counting program, thereby allowing rapid and automated cell counting of nucleated
      white blood cells and non-nucleated red blood cells in fluorescence and bright
      field images. Using these unique features, we successfully demonstrate the
      ability of our counting platform to measure low CSF cell counts without sample
      preparation.

PMID- 29642426
TI  - Impact of Rodenticides on the Coagulation Properties of Milk.
AB  - In this study, we investigated the impact of the rodenticides (strychnine,
      bromadiolone, and brodifacoum) on milk pH, rennet coagulation time (RCT), and
      coagulum strength. Sub-lethal amounts of strychnine and bromadiolone produced an
      unnaturally large change in milk pH, compared to brodifacoum and brodifacoum on
      milk coagulation properties. All three studied rodenticides significantly
      affected RCT and coagulum strength. The presence of sub-lethal amounts of each
      individual rodenticide increased RCT by an overall mean of 17% (p < 0.001).
      Rodenticide contamination decreased coagulum strength by an overall mean of 26%
      (p < 0.05). Our results suggest that such changes could be noticeable at the
      farm, thus, potentially averting the mixture of contaminated milk with the tanker
      supply, and preventing downstream distribution to consumers.

PMID- 29642425
TI  - Lutein and Zeaxanthin Are Positively Associated with Visual-Spatial Functioning
      in Older Adults: An fMRI Study.
AB  - Lutein (L) and zeaxanthin (Z) are two xanthophyll carotenoids that have
      antioxidant and anti-inflammatory properties. Previous work has demonstrated
      their importance for eye health and preventing diseases such as age-related
      macular degeneration. An emerging literature base has also demonstrated the
      importance of L and Z in cognition, neural structure, and neural efficiency. The
      present study aimed to better understand the mechanisms by which L and Z relate
      to cognition, in particular, visual-spatial processing and decision-making in
      older adults. We hypothesized that markers of higher levels of L and Z would be
      associated with better neural efficiency during a visual-spatial processing task.
      L and Z were assessed via standard measurement of blood serum and retinal
      concentrations. Visual-spatial processing and decision-making were assessed via a
      judgment of line orientation task (JLO) completed during a functional magnetic
      resonance imaging (fMRI) scan. The results demonstrated that individuals with
      higher concentrations of L and Z showed a decreased blood-oxygen-level dependent
      (BOLD) signal during task performance (i.e., "neural efficiency") in key areas
      associated with visual-spatial perception, processing, decision-making, and motor
      coordination, including the lateral occipital cortex, occipital pole, superior
      and middle temporal gyri, superior parietal lobule, superior and middle frontal
      gyri, and pre- and post-central gyri. To our knowledge, this is the first
      investigation of the relationship of L and Z to visual-spatial processing at a
      neural level using in vivo methodology. Our findings suggest that L and Z may
      impact brain health and cognition in older adults by enhancing neurobiological
      efficiency in a variety of regions that support visual perception and decision
      making.

PMID- 29642427
TI  - Laboratory Investigation Comparing Plaque Removal Efficacy of Two Novel-Design
      Toothbrushes with Different Brushing Techniques.
AB  - Manufacturers of manual toothbrushes have improved novel brush head designs aimed
      at achieving good plaque removal even with inadequate brushing technique. This
      study tested the plaque removal efficacy of two novel designs compared with a
      flat trimmed toothbrush with different brushing techniques. Two novel-design
      toothbrushes (Colgate(r) 360 degrees  Surround and Oral-B(r) Pro-HealthTM
      Clinical Pro-Flex) were tested. The control toothbrush was Butler(r) GUM 311.
      Artificial plaque was applied on artificial teeth. Brushing with the modified
      Bass and horizontal scrub technique was then performed independently. After
      brushing, the remaining plaque index and Proximal Marginal Index (PMI) were
      evaluated. With the same brushing technique, there was no statistically
      significant difference in the mean of the whole mouth plaque scores or PMI among
      the three different toothbrush designs with neither brushing techniques (p >
      0.05). When a comparison was made between the mean PMI of the two brushing
      techniques in each toothbrush design, Colgate(r) showed no statistically
      significant difference with either brushing technique (p > 0.05), but Butler(r)
      and Oral-B(r) showed statistically significantly less PMI with modified Bass
      technique than with horizontal scrub technique (p < 0.05). No difference in the
      whole mouth plaque removal efficacy was found among the three different
      toothbrush designs with either brushing technique.

PMID- 29642428
TI  - Consumption of 100% Pure Fruit Juice and Dietary Quality in French Adults:
      Analysis of a Nationally Representative Survey in the Context of the WHO
      Recommended Limitation of Free Sugars.
AB  - Sugar-containing beverages are often seen as a negative influence on diet quality
      and body weight control. The present study examines the consumption of 100% fruit
      juice (FJ) based on a seven-day dietary survey in a representative sample of
      French adults (n = 1607). About a half of the participants (44%) consumed FJ,
      most often at breakfast time (60%). Average intake in FJ consumers was 115.6 +/-
      4.0 mL/day (46.3 +/- 1.7 kcal/day). Prevalence of consumption increased with
      education and income and decreased with age, but no association was observed with
      body mass index (BMI), physical activity, or smoking. In consumers, FJ brought 2%
      daily energy and contributed larger proportions of vitamins (B1 7%, B2 3%, B5 5%,
      B6 6%, B9 10%, C 32%, E 9%, beta-carotene 5%), minerals (magnesium 4%, potassium
      7%), and free sugars (19%). FJ consumers ingested more whole fruits, vegetables,
      and many other foods than non-consumers did. Free sugars represented 11.2% of the
      daily energy in FJ consumers versus 8.6% in non-consumers. This cross-sectional
      survey reveals that FJ contributes to diet quality without association with
      excess body weight. These observations should be confirmed in longitudinal
      studies. They support the view that contribution to diet quality should be
      specifically recognized in the context of the World Health Organization (WHO)
      recommended decrease of free sugar intake.

PMID- 29642429
TI  - Thermomechanical Studies of Yielding and Strain Localization Phenomena of Gum
      Metal under Tension.
AB  - This paper presents results of investigation of multifunctional beta-Ti alloy Gum
      Metal subjected to tension at various strain rates. Digital image correlation was
      used to determine strain distributions and stress-strain curves, while infrared
      camera allowed for us to obtain the related temperature characteristics of the
      specimen during deformation. The mechanical curves completed by the temperature
      changes were applied to analyze the subsequent stages of the alloy loading.
      Elastic limit, recoverable strain, and development of the strain localization
      were studied. It was found that the maximal drop in temperature, which
      corresponds to the yield limit of solid materials, was referred to a
      significantly lower strain value in the case of Gum Metal in contrast to its
      large recoverable strain. The temperature increase proves a dissipative character
      of the process and is related to presence of omega and alpha" phases induced
      during the alloy fabrication and their exothermic phase transformations activated
      under loading. During plastic deformation, both the strain and temperature
      distributions demonstrate that strain localization for higher strain rates starts
      nucleating just after the yield limit leading to specimen necking and rupture.
      Macroscopically, it is exhibited as softening of the stress-strain curve in
      contrast to the strain hardening observed at lower strain rates.

PMID- 29642430
TI  - Oxadiazole-Based Highly Efficient Bipolar Fluorescent Emitters for Organic Light
      Emitting Diodes.
AB  - In this study, a series of bipolar fluorescence emitters named 2DPAc-OXD, DPAc
      OXD, 2PTZ-OXD and PTZ-OXD were designed and synthesized with excellent yields.
      The characterization of materials was investigated by using nuclear magnetic
      resonance (NMR) (1H, 13C), mass spectrometry and thermogravimetric analysis
      (TGA). To investigate device efficiencies, two different OLED devices (Device 1,
      Device 2) were fabricated with two different host materials (Bepp2, DPEPO). The
      Device 2 with 2PTZ-OXD as fluorescent emitter exhibited excellent power and
      current efficiencies of 6.88 Lm/W and 10.10 cd/A, respectively. The external
      quantum efficiency of 2PTZ-OXD was around 3.99% for Device 2. The overall device
      properties of phenothiazine donor were better than acridine derivatives.

PMID- 29642432
TI  - Mobile User Connectivity in Relay-Assisted Visible Light Communications.
AB  - In this paper, we investigate relay-assisted visible light communications (VLC)
      where a mobile user acts as a relay and forwards data from a transmitter to the
      end mobile user. We analyse the utilization of the amplify-and-forward (AF) and
      decode-and-forward (DF) relaying schemes. The focus of the paper is on analysis
      of the behavior of the mobile user acting as a relay while considering a
      realistic locations of the receivers and transmitters on a standard mobile phone,
      more specifically with two photodetectors on both sides of a mobile phone and a
      transmitting LED array located upright. We also investigate dependency of the bit
      error rate (BER) performance on the azimuth and elevation angles of the mobile
      relay device within a typical office environment. We provide a new analytical
      description of BER for AF and DF-based relays in VLC. In addition we compare AF
      and DF-based systems and show that DF offers a marginal improvement in the
      coverage area with a BER < 10-3 and a data rate of 100 Mb/s. Numerical results
      also illustrate that relay-based systems offer a significant improvement in terms
      of the coverage compared to direct non-line of sight VLC links.

PMID- 29642431
TI  - The Recombinant Inhibitor of DNA Binding Id2 Forms Multimeric Structures via the
      Helix-Loop-Helix Domain and the Nuclear Export Signal.
AB  - The inhibitor of DNA binding and cell differentiation 2 (Id2) is a helix-loop
      helix (HLH) protein that acts as negative dominant regulator of basic-HLH
      transcription factors during development and in cancer. The structural properties
      of Id2 have been investigated so far by using synthetic or recombinant fragments
      reproducing single domains (N-terminus, HLH, C-terminus): the HLH domain tends to
      dimerize into a four-helix bundle, whereas the flanking regions are flexible. In
      this work, the intact protein was expressed in E. coli, solubilized from
      inclusion bodies with urea, purified and dissolved in water at pH~4. Under these
      conditions, Id2 was obtained with both cysteine residues disulfide-bonded to beta
      mercaptoethanol that was present during the solubilization process. Moreover, it
      existed in a self-assembled state, in which the N-terminus remained highly
      flexible, while the HLH domain and, surprisingly, part of the C-terminus, which
      corresponds to the nuclear export signal (NES), both were involved in slowly
      tumbling, rigid structures. The protein oligomers also formed twisted fibrils
      that were several micrometers long and up to 80 nm thick. These results show that
      self-assembly decreases the backbone flexibility of those two protein regions
      (HLH and NES) that are important for interaction with basic-HLH transcription
      factors or for nucleocytoplasmic shuttling.

PMID- 29642433
TI  - Spatially Correlated, Single Nanomaterial-Level Structural and Optical Profiling
      of Cu-Doped ZnO Nanorods Synthesized via Multifunctional Silicides.
AB  - We demonstrate a straightforward and effective method to synthesize vertically
      oriented, Cu-doped ZnO nanorods (NRs) using a novel multipurpose platform of
      copper silicide nanoblocks (Cu3Si NBs) preformed laterally in well-defined
      directions on Si. The use of the surface-organized Cu3Si NBs for ZnO NR growth
      successfully results in densely assembled Cu-doped ZnO NRs on each NB platform,
      whose overall structures resemble thick bristles on a brush head. We show that
      Cu3Si NBs can uniquely serve as a catalyst for ZnO NRs, a local dopant source of
      Cu, and a prepatterned guide to aid the local assembly of the NRs on the growth
      substrate. We also ascertain the crystalline structures, optical properties, and
      spectroscopic signatures of the Cu-doped ZnO NRs produced on the NBs, both at
      each module of NRs/NB and at their ensemble level. Subsequently, we determine
      their augmented properties relative to the pristine form of undoped ZnO NRs and
      the source material of Cu3Si NBs. We provide spatially correlated structural and
      optical data for individual modules of Cu-doped ZnO NRs assembled on a Cu3Si NB
      by resolving them along the different positions on the NB. Ensemble-averaged
      versus individual behaviors of Cu-doped ZnO NRs on Cu3Si NBs are then compared.
      We further discuss the potential impact of such ZnO-derived NRs on their
      relatively unexplored biological and biomedical applications. Our efforts will be
      particularly useful when exploiting each integrated module of self-aligned, Cu
      doped ZnO NRs on a NB as a discretely addressable, active element in solid-state
      sensors and miniaturized luminescent bioprobes.

PMID- 29642435
TI  - Effects of N2 Partial Pressure on Growth, Structure, and Optical Properties of
      GaN Nanorods Deposited by Liquid-Target Reactive Magnetron Sputter Epitaxy.
AB  - GaN nanorods, essentially free from crystal defects and exhibiting very sharp
      band-edge luminescence, have been grown by reactive direct-current magnetron
      sputter epitaxy onto Si (111) substrates at a low working pressure of 5 mTorr.
      Upon diluting the reactive N2 working gas with a small amount of Ar (0.5 mTorr),
      we observed an increase in the nanorod aspect ratio from 8 to ~35, a decrease in
      the average diameter from 74 to 35 nm, and a two-fold increase in nanorod
      density. With further dilution (Ar = 2.5 mTorr), the aspect ratio decreased to
      14, while the diameter increased to 60 nm and the nanorod density increased to a
      maximum of 2.4 * 108 cm-2. Yet, lower N2 partial pressures eventually led to the
      growth of continuous GaN films. The observed morphological dependence on N2
      partial pressure is explained by a change from N-rich to Ga-rich growth
      conditions, combined with reduced GaN-poisoning of the Ga-target as the N2 gas
      pressure is reduced. Nanorods grown at 2.5 mTorr N2 partial pressure exhibited a
      high intensity 4 K photoluminescence neutral donor bound exciton transitions
      (D0XA) peak at ~3.479 eV with a full-width-at-half-maximum of 1.7 meV. High
      resolution transmission electron microscopy corroborated the excellent
      crystalline quality of the nanorods.

PMID- 29642434
TI  - A Single Dose of Atorvastatin Applied Acutely after Spinal Cord Injury Suppresses
      Inflammation, Apoptosis, and Promotes Axon Outgrowth, Which Might Be Essential
      for Favorable Functional Outcome.
AB  - The aim of our study was to limit the inflammatory response after a spinal cord
      injury (SCI) using Atorvastatin (ATR), a potent inhibitor of cholesterol
      biosynthesis. Adult Wistar rats were divided into five experimental groups: one
      control group, two Th9 compression (40 g/15 min) groups, and two Th9 compression
      + ATR (5 mg/kg, i.p.) groups. The animals survived one day and six weeks. ATR
      applied in a single dose immediately post-SCI strongly reduced IL-1beta release
      at 4 and 24 h and considerably reduced the activation of resident cells at one
      day post-injury. Acute ATR treatment effectively prevented the excessive
      infiltration of destructive M1 macrophages cranially, at the lesion site, and
      caudally (by 66%, 62%, and 52%, respectively) one day post-injury, whereas the
      infiltration of beneficial M2 macrophages was less affected (by 27%, 41%, and
      16%). In addition, at the same time point, ATR visibly decreased caspase-3
      cleavage in neurons, astrocytes, and oligodendrocytes. Six weeks post-SCI, ATR
      increased the expression of neurofilaments in the dorsolateral columns and Gap43
      positive fibers in the lateral columns around the epicenter, and from day 30 to
      42, significantly improved the motor activity of the hindlimbs. We suggest that
      early modulation of the inflammatory response via effects on the M1/M2
      macrophages and the inhibition of caspase-3 expression could be crucial for the
      functional outcome.

PMID- 29642436
TI  - Radon Levels in Indoor Environments of the University Hospital in Bari-Apulia
      Region Southern Italy.
AB  - Since 1988, the International Agency for Research on Cancer (IARC) has classified
      radon among the compounds for which there is scientific evidence of
      carcinogenicity for humans (group 1). The World Health Organization (WHO)
      recommends a reference radon level between 100 and 300 Bq/m3 for homes. The
      objective of this study is to measure the radon concentrations in 401 workplaces,
      different from the patient rooms, in 28 different buildings of the university
      hospital in Bari (Apulia region, Southern Italy) to evaluate the exposure of
      health care workers. Radon environmental sampling is performed over two
      consecutive six-month periods via the use of passive dosimeters of the CR-39
      type. We find an average annual radon concentration expressed as median value of
      48.0 Bq/m3 (range 6.5-388.0 Bq/m3) with a significant difference between the two
      six-month periods (median value: February/July 41.0 Bq/m3 vs. August/January 55.0
      Bq/m3). An average concentration of radon lower than the WHO reference level (100
      Bq/m3) is detected in 76.1% of monitored environments, while higher than 300
      Bq/m3 only in the 0.9%. Most workplaces report radon concentrations within the
      WHO reference level, therefore, the risk to workers' health deriving from
      occupational exposure to radon can be considered to be low. Nevertheless, the
      goal is to achieve near-zero exposures to protect workers' health.

PMID- 29642439
TI  - d-Amino Acids Are Exuded by Arabidopsis thaliana Roots to the Rhizosphere.
AB  - Proteinogenic l-amino acids (l-AAs) are essential in all kingdoms as building
      blocks of proteins. Their d-enantiomers are also known to fulfill important
      functions in microbes, fungi, and animals, but information about these molecules
      in plants is still sparse. Previously, it was shown that d-amino acids (d-AAs)
      are taken up and utilized by plants, but their ways to reduce excessive amounts
      of them still remained unclear. Analyses of plant d-AA content after d-Ala and d
      Glu feeding opened the question if exudation of d-AAs into the rhizosphere takes
      place and plays a role in the reduction of d-AA content in plants. The exudation
      of d-Ala and d-Glu could be confirmed by amino acid analyses of growth media from
      plants treated with these d-AAs. Further tests revealed that other d-AAs were
      also secreted. Nevertheless, treatments with d-Ala and d-Glu showed that plants
      are still able to reduce their contents within the plant without exudation.
      Further exudation experiments with transport inhibitors revealed that d-AA root
      exudation is rather passive and comparable to the secretion of l-AAs. Altogether,
      these observations argued against a dominant role of exudation in the regulation
      of plant d-AA content, but may influence the composition of the rhizosphere.

PMID- 29642437
TI  - Photodynamic Effect of Methylene Blue and Low Level Laser Radiation in Head and
      Neck Squamous Cell Carcinoma Cell Lines.
AB  - Photodynamic therapy (PDT) is suggested to have an impact on the treatment of
      early stage head and neck cancers (HNSCC). We investigated the effect of PDT with
      methylene blue (MB) and a diode laser (660 nm) as the laser source on HNSCC cell
      lines as an in vitro model of surface oral squamous cell carcinoma. Cell-cultures
      were exposed to 160 uM MB for 4 min and to laser light for 8 min. Viability was
      proven via cell viability assay and clonogenic survival via clone counting assay.
      The combination of MB and diode laser evidenced high efficient loss of cell
      viability by 5% of the control, while treatment with the same concentration of MB
      for 4 min alone showed a viability of 46% of the control. In both SCC-25 and
      Detroit 562 HNSCC cells, MB combined with the laser allowed a significant
      abrogation of clonogenic growth (p < 0.01), especially in the case of Detroit 562
      cells less than 1% of the suspension plated cells were able to grow tumor cell
      nests. Multiresistant (Detroit 562) HNSCC cells expressing cancer stem cell
      markers are sensitive to MB/red laser combined PDT.

PMID- 29642438
TI  - Sesamol Inhibited Melanogenesis by Regulating Melanin-Related Signal Transduction
      in B16F10 Cells.
AB  - Melanin is synthesized through a series of interactions catalyzed by melanogenic
      enzymes such as tyrosinase, dopachrome tautomerase (tyrosinase-related protein-2;
      TRP-2), and tyrosinase-related protein-1 (TRP-1). Tyrosinase plays a key role in
      catalysing the initial and limiting steps of melanogenesis. The melanin that
      results from melanogenesis has the protective effect of absorbing ultraviolet
      radiation. However, overproduction of melanin, in addition to altering the
      appearance of skin, may lead to skin disorders such as melasma, solar lentigo,
      and postinflammatory hyperpigmentation. Previous studies have revealed that
      sesamol is a strong antioxidant and a free radical scavenger. In this study, we
      investigated the effects of sesamol on the regulation of melanogenesis and
      related mechanisms in B16F10 cells. The results indicated that sesamol inhibited
      tyrosinase activity and melanogenesis induced by alpha-melanocyte-stimulating
      hormone (alpha-MSH) in B16F10 melanoma cells. Sesamol decreased the protein level
      of melanocortin 1 receptor (MC1R), microphthalmia-associated transcription factor
      (MITF), tyrosinase, and TRP-1 by downregulating cyclic adenosine monophosphate
      (cAMP)/protein kinase A (PKA) pathways that had been activated by alpha-MSH.
      Sesamol increased glycogen synthase kinase 3 beta (GSK3beta), protein kinase B
      (AKT), and extracellular signal-related kinase (ERK) phosphorylation, thus
      inhibiting the transcription of MITF. Sesamol also inhibited melanin synthesis
      and tyrosinase expression by modulating ERK, phosphoinositide 3-kinase
      (PI3K)/AKT, p38, and c-Jun amino-terminal kinase (JNK) signalling pathways. These
      results indicate that sesamol acted as a potent depigmenting agent.

PMID- 29642440
TI  - Global and Complement Gene-Specific DNA Methylation in Grass Carp after Grass
      Carp Reovirus (GCRV) Infection.
AB  - Grass carp reovirus (GCRV) causes huge economic loss to the grass carp
      cultivation industry but the mechanism remains largely unknown. In this study, we
      investigated the global and complement gene-specific DNA methylation in grass
      carp after GCRV infection aimed to uncover the mechanism underlying GCRV
      infection. The global DNA methylation level was increased after GCRV infection.
      Expression levels of enzymes involved in DNA methylation including DNA
      methyltransferase (DNMT), ten-eleven translocation proteins (TETs), and glycine N
      methyltransferase (GNMT) were significantly altered after GCRV infection. In
      order to investigate the relationship between the gene expression level and DNA
      methylation level, two representative complement genes, complement component 3
      (C3) and kininogen-1 (KNG1), were selected for further analysis. mRNA expression
      levels of the two genes were significantly increased at 5 and 7 days after GCRV
      infection, whereas the DNA methylation level at the 5' flanking regions of the
      two genes were down-regulated at the same time-points. Moreover, a negative
      correlation was detected between gene expression levels and DNA methylation
      levels of the two genes. Therefore, the current data revealed a global and
      complement gene-specific DNA methylation profile after GCRV infection. Our study
      would provide new insights into understanding the mechanism underlying GCRV
      infection.

PMID- 29642441
TI  - Transcriptome Profile in Unilateral Adrenalectomy-Induced Compensatory Adrenal
      Growth in the Rat.
AB  - Compensatory adrenal growth evoked by unilateral adrenalectomy
      (hemiadrenalectomy) constitutes one of the most frequently studied in vivo models
      of adrenocortical enlargement. This type of growth has been quite well
      characterized for its morphological, biochemical, and morphometric parameters.
      However, the molecular basis of compensatory adrenal growth is poorly understood.
      Therefore, the aim of this study was to investigate the rat adrenal transcriptome
      profile during the time of two previously described adrenocortical proliferation
      waves at 24 and 72 h after unilateral adrenalectomy. Surgical removal of the left
      adrenal or a sham operation was accomplished via the classic dorsal approach. As
      expected, the weight of the remaining right adrenal glands collected at 24 and 72
      h after hemiadrenalectomy increased significantly. The transcriptome profile was
      identified by means of Affymetrix(r) Rat Gene 2.1 ST Array. The general profiles
      of differentially expressed genes were visualized as volcano plots and heatmaps.
      Detailed analyzes consisted of identifying significantly enriched gene
      ontological groups relevant to adrenal physiology, by means of DAVID and GOplot
      bioinformatics tools. The results of our studies showed that compensatory adrenal
      growth induced by unilateral adrenalectomy exerts a limited influence on the
      global transcriptome profile of the rat adrenal gland; nevertheless, it leads to
      significant changes in the expression of key genes regulating the circadian
      rhythm. Our results confirm also that regulation of compensatory adrenal growth
      is under complex and multifactorial control with a pivotal role of neural
      regulatory mechanisms and a supportive role of other components.

PMID- 29642442
TI  - Baculovirus PTP2 Functions as a Pro-Apoptotic Protein.
AB  - The family Baculoviridae encompasses a large number of invertebrate viruses,
      mainly infecting caterpillars of the order Lepidoptera. The baculovirus
      Spodoptera exigua multiple nucleopolyhedrovirus (SeMNPV) induces physiological
      and behavioral changes in its host Spodoptera exigua, as well as immunological
      responses, which may affect virus transmission. Here we show that the SeMNPV
      encoded protein tyrosine phosphatase 2 (PTP2) induces mild apoptosis in
      Spodoptera frugiperda (Sf) 21 cells upon transient expression. Transient
      expression of a catalytic-site mutant of ptp2 did not lead to apoptosis,
      indicating that the phosphatase activity of PTP2 is needed to induce apoptosis.
      We also found that the caspase level (indicator of apoptosis) was higher in cells
      transfected with the ptp2 gene than in cells transfected with the catalytic
      mutant. Adding a caspase inhibitor reduced the level of ptp2-induced apoptosis.
      Moreover, deletion of the ptp2 gene from the viral genome prevented the induction
      of apoptosis in S. exigua hemocytes. The virus titer and virulence indices (the
      viral infectivity and the time to death) were not affected by deletion of the
      ptp2 gene. However, the viral occlusion body yield from S. exigua larvae infected
      with the mutant virus lacking the ptp2 gene was much lower than the yield from
      larvae infected with the wild-type (WT) virus. We hypothesize that the observed
      pro-apoptotic effects of PTP2 are the result of PTP2-mediated immune suppression
      in larvae, which consequently leads to higher viral occlusion body yields.

PMID- 29642443
TI  - Association between Urinary Aflatoxin (AFM1) and Dietary Intake among Adults in
      Hulu Langat District, Selangor, Malaysia.
AB  - Aflatoxin is a food contaminant and its exposure through the diet is frequent and
      ubiquitous. A long-term dietary aflatoxin exposure has been linked to the
      development of liver cancer in populations with high prevalence of aflatoxin
      contamination in foods. Therefore, this study was conducted to identify the
      association between urinary aflatoxin M1 (AFM1), a biomarker of aflatoxin
      exposure, with the dietary intake among adults in Hulu Langat district, Selangor,
      Malaysia. Certain food products have higher potential for aflatoxin contamination
      and these were listed in a Food Frequency Questionnaire, which was given to all
      study participants. This allowed us to record consumption rates for each food
      product listed. Concomitantly, urine samples were collected, from adults in
      selected areas in Hulu Langat district, for the measurement of AFM1 levels using
      an ELISA kit. Of the 444 urine samples collected and tested, 199 were positive
      for AFM1, with 37 of them exceeding the limit of detection (LOD) of 0.64 ng/mL.
      Cereal products showed the highest consumption level among all food groups, with
      an average intake of 512.54 g per day. Chi-square analysis showed that
      consumption of eggs (X2 = 4.77, p = 0.03) and dairy products (X2 = 19.36, p <
      0.01) had significant associations with urinary AFM1 but both food groups were
      having a phi and Cramer's V value that less than 0.3, which indicated that the
      association between these food groups' consumption and AFM1 level in urine was
      weak.

PMID- 29642444
TI  - Nutritionally Optimized, Culturally Acceptable, Cost-Minimized Diets for Low
      Income Ghanaian Families Using Linear Programming.
AB  - The Ghanaian population suffers from a double burden of malnutrition. Cost of
      food is considered a barrier to achieving a health-promoting diet. Food prices
      were collected in major cities and in rural areas in southern Ghana. Linear
      programming (LP) was used to calculate nutritionally optimized diets (food
      baskets (FBs)) for a low-income Ghanaian family of four that fulfilled energy and
      nutrient recommendations in both rural and urban settings. Calculations included
      implementing cultural acceptability for families living in extreme and moderate
      poverty (food budget under USD 1.9 and 3.1 per day respectively). Energy
      appropriate FBs minimized for cost, following Food Balance Sheets (FBS), lacked
      key micronutrients such as iodine, vitamin B12 and iron for the mothers.
      Nutritionally adequate FBs were achieved in all settings when optimizing for a
      diet cheaper than USD 3.1. However, when delimiting cost to USD 1.9 in rural
      areas, wild foods had to be included in order to meet nutritional adequacy.
      Optimization suggested to reduce roots, tubers and fruits and to increase
      cereals, vegetables and oil-bearing crops compared with FBS. LP is a useful tool
      to design culturally acceptable diets at minimum cost for low-income Ghanaian
      families to help advise national authorities how to overcome the double burden of
      malnutrition.

PMID- 29642445
TI  - Effect of Gypsum on the Early Hydration of Cubic and Na-Doped Orthorhombic
      Tricalcium Aluminate.
AB  - The tricalcium aluminate (C3A) and sulfate content in cement influence the
      hydration chemistry, setting time and rheology of cement paste, mortar and
      concrete. Here, in situ experiments are performed to better understand the effect
      of gypsum on the early hydration of cubic (cub-)C3A and Na-doped orthorhombic
      (orth-)C3A. The isothermal calorimetry data show that the solid-phase assemblage
      produced by the hydration of C3A is greatly modified as a function of its crystal
      structure type and gypsum content, the latter of which induces non-linear changes
      in the heat release rate. These data are consistent with the in situ X-ray
      diffraction results, which show that a higher gypsum content accelerates the
      consumption of orth-C3A and the subsequent precipitation of ettringite, which is
      contrary to the cub-C3A system where gypsum retarded the hydration rate. These in
      situ results provide new insight into the relationship between the chemistry and
      early-age properties of cub- and orth-C3A hydration and corroborate the reported
      ex situ findings of these systems.

PMID- 29642446
TI  - Scalable Fabrication of High-Performance Transparent Conductors Using Graphene
      Oxide-Stabilized Single-Walled Carbon Nanotube Inks.
AB  - Recent development in liquid-phase processing of single-walled carbon nanotubes
      (SWNTs) has revealed rod-coating as a promising approach for large-scale
      production of SWNT-based transparent conductors. Of great importance in the ink
      formulation is the stabilizer having excellent dispersion stability,
      environmental friendly and tunable rheology in the liquid state, and also can be
      readily removed to enhance electrical conductivity and mechanical stability.
      Herein we demonstrate the promise of graphene oxide (GO) as a synergistic
      stabilizer for SWNTs in water. SWNTs dispersed in GO is formulated into inks with
      homogeneous nanotube distribution, good wetting and rheological properties, and
      compatible with industrial rod coating practice. Microwave treatment of rod
      coated films can reduce GOs and enhance electro-optical performance. The
      resultant films offer a sheet resistance of ~80 Omega/sq at 86% transparency,
      along with good mechanical flexibility. Doping the films with nitric acid can
      further decrease the sheet resistance to ~25 Omega/sq. Comparing with the films
      fabricated from typical surfactant-based SWNT inks, our films offer superior
      adhesion as assessed by the Scotch tape test. This study provides new insight
      into the selection of suitable stabilizers for functional SWNT inks with strong
      potential for printed electronics.

PMID- 29642448
TI  - Microstructure, Mechanical Properties, and Corrosion Resistance of
      Thermomechanically Processed AlZn6Mg0.8Zr Alloy.
AB  - The paper presents results of the investigations on the effect of low-temperature
      thermomechanical treatment (LTTT) on the microstructure of AlZn6Mg0.8Zr alloy
      (7000 series) and its mechanical properties as well as electrochemical and stress
      corrosion resistance. For comparison of the LTTT effect, the alloy was subjected
      to conventional precipitation hardening. Comparative studies were conducted in
      the fields of metallographic examinations and static tensile tests. It was found
      that mechanical properties after the LTTT were better in comparison to after
      conventional heat treatment (CHT). The tested alloy after low-temperature
      thermomechanical treatment with increasing plastic deformation shows decreased
      electrochemical corrosion resistance during potentiodynamic tests. The alloy
      after low-temperature thermomechanical treatment with deformation degree in the
      range of 10 to 30% is characterized by a high resistance to stress corrosion
      specified by the level of PSCC indices.

PMID- 29642447
TI  - MitoQ Loaded Chitosan-Hyaluronan Composite Membranes for Wound Healing.
AB  - Two self-associating biopolymers, namely chitosan (Ch) and a high-molar-mass
      hyaluronan (HA), were used to prepare membranes with the aim to protect and to
      enhance the healing of injured skin. A mitochondrially-targeted antioxidant-MitoQ
      was incorporated into the mixture of biopolymers prior to their self-association.
      These three-component membranes were evaluated in detail utilising surface
      roughness measurements, contact angle measurements, hemocompatibility, and
      thrombogenicity analyses. Furthermore, in vivo application of Ch/HA/MitoQ
      membranes was assessed on injured rabbit and rat skin utilizing histological
      methods. The results showed that the prepared thrombogenic Ch/HA/MitoQ membranes
      had higher roughness, which allowed for greater surface area for tissue membrane
      interaction during the healing processes, and lower cytotoxicity levels than
      controls. MitoQ-loaded composite membranes displayed superior healing properties
      in these animal models compared to control membranes.

PMID- 29642449
TI  - Characterization of a New Staphylococcus aureus Kayvirus Harboring a Lysin Active
      against Biofilms.
AB  - Staphylococcus aureus is one of the most relevant opportunistic pathogens
      involved in many biofilm-associated diseases, and is a major cause of nosocomial
      infections, mainly due to the increasing prevalence of multidrug-resistant
      strains. Consequently, alternative methods to eradicate the pathogen are urgent.
      It has been previously shown that polyvalent staphylococcal kayviruses and their
      derived endolysins are excellent candidates for therapy. Here we present the
      characterization of a new bacteriophage: vB_SauM-LM12 (LM12). LM12 has a broad
      host range (>90%; 56 strains tested), and is active against several MRSA strains.
      The genome of LM12 is composed of a dsDNA molecule with 143,625 bp, with average
      GC content of 30.25% and codes for 227 Coding Sequences (CDSs). Bioinformatics
      analysis did not identify any gene encoding virulence factors, toxins, or
      antibiotic resistance determinants. Antibiofilm assays have shown that this phage
      significantly reduced the number of viable cells (less than one order of
      magnitude). Moreover, the encoded endolysin also showed activity against
      biofilms, with a consistent biomass reduction during prolonged periods of
      treatment (of about one order of magnitude). Interestingly, the endolysin was
      shown to be much more active against stationary-phase cells and suspended biofilm
      cells than against intact and scraped biofilms, suggesting that cellular
      aggregates protected by the biofilm matrix reduced protein activity. Both phage
      LM12 and its endolysin seem to have a strong antimicrobial effect and broad host
      range against S. aureus, suggesting their potential to treat S. aureus biofilm
      infections.

PMID- 29642450
TI  - Mechanistic Insights into the Stimulant Properties of Novel Psychoactive
      Substances (NPS) and Their Discrimination by the Dopamine Transporter-In Silico
      and In Vitro Exploration of Dissociative Diarylethylamines.
AB  - Novel psychoactive substances (NPS) may have unsuspected addiction potential
      through possessing stimulant properties. Stimulants normally act at the dopamine
      transporter (DAT) and thus increase dopamine (DA) availability in the brain,
      including nucleus accumbens, within the reward and addiction pathway. This paper
      aims to assess DAT responses to dissociative diarylethylamine NPS by means of in
      vitro and in silico approaches. We compared diphenidine (DPH) and 2
      methoxydiphenidine (methoxphenidine, 2-MXP/MXP) for their binding to rat DAT,
      using autoradiography assessment of [125I]RTI-121 displacement in rat striatal
      sections. The drugs' effects on electrically-evoked DA efflux were measured by
      means of fast cyclic voltammetry in rat accumbens slices. Computational modeling,
      molecular dynamics and alchemical free energy simulations were used to analyse
      the atomistic changes within DAT in response to each of the five dissociatives:
      DPH, 2-MXP, 3-MXP, 4-MXP and 2-Cl-DPH, and to calculate their relative binding
      free energy. DPH increased DA efflux as a result of its binding to DAT, whereas
      MXP had no significant effect on either DAT binding or evoked DA efflux. Our
      computational findings corroborate the above and explain the conformational
      responses and atomistic processes within DAT during its interactions with the
      dissociative NPS. We suggest DPH can have addictive liability, unlike MXP,
      despite the chemical similarities of these two NPS.

PMID- 29642452
TI  - A Novel Approach for Evaluating the Contraction of Hypo-Peritectic Steels during
      Initial Solidification by Surface Roughness.
AB  - The contraction of peritectic steels in the initial solidification has an
      important influence on the formation of surface defects of continuously cast
      slabs. In order to understand the contraction behavior of the initial
      solidification of steels in the mold, the solidification process and surface
      roughness in a commercial hypo-peritectic and several non-peritectic steels were
      investigated using Confocal Scanning Laser Microscope (CSLM). The massive
      transformation of delta-Fe (delta) to austenite (gamma) was documented in the
      hypo-peritectic steel, which caused surface wrinkles and greatly increases the
      surface roughness of samples in the experiments. Surface roughness (Ra(delta
      >gamma)) was calculated to evaluate the contraction level of the hypo-peritectic
      steel due to delta-gamma transformation. The result shows that the surface
      roughness method can facilitate the estimation of the contraction level of
      peritectic transformation over a wide range of cooling rates.

PMID- 29642451
TI  - Should We Prescribe More Protein to Critically Ill Patients?
AB  - In the context of critical illness, evidence suggests that exogenous
      protein/amino acid supplementation has the potential to favorably impact whole
      body protein balance. Whether this translates into retention of muscle, greater
      muscle strength, and improved survival and physical recovery of critically ill
      patients remains uncertain. The purpose of this brief commentary is to provide an
      overview of the clinical evidence for and against increasing protein doses and to
      introduce two new trials that will add considerably to our evolving understanding
      of protein requirements in the critically ill adult patient.

PMID- 29642454
TI  - Application of Deep Learning Architectures for Accurate and Rapid Detection of
      Internal Mechanical Damage of Blueberry Using Hyperspectral Transmittance Data.
AB  - Deep learning has become a widely used powerful tool in many research fields,
      although not much so yet in agriculture technologies. In this work, two deep
      convolutional neural networks (CNN), viz. Residual Network (ResNet) and its
      improved version named ResNeXt, are used to detect internal mechanical damage of
      blueberries using hyperspectral transmittance data. The original structure and
      size of hypercubes are adapted for the deep CNN training. To ensure that the
      models are applicable to hypercube, we adjust the number of filters in the
      convolutional layers. Moreover, a total of 5 traditional machine learning
      algorithms, viz. Sequential Minimal Optimization (SMO), Linear Regression (LR),
      Random Forest (RF), Bagging and Multilayer Perceptron (MLP), are performed as the
      comparison experiments. In terms of model assessment, k-fold cross validation is
      used to indicate that the model performance does not vary with the different
      combination of dataset. In real-world application, selling damaged berries will
      lead to greater interest loss than discarding the sound ones. Thus, precision,
      recall, and F1-score are also used as the evaluation indicators alongside
      accuracy to quantify the false positive rate. The first three indicators are
      seldom used by investigators in the agricultural engineering domain. Furthermore,
      ROC curves and Precision-Recall curves are plotted to visualize the performance
      of classifiers. The fine-tuned ResNet/ResNeXt achieve average accuracy and F1
      score of 0.8844/0.8784 and 0.8952/0.8905, respectively. Classifiers SMO/
      LR/RF/Bagging/MLP obtain average accuracy and F1-score of
      0.8082/0.7606/0.7314/0.7113/0.7827 and 0.8268/0.7796/0.7529/0.7339/0.7971,
      respectively. Two deep learning models achieve better classification performance
      than the traditional machine learning methods. Classification for each testing
      sample only takes 5.2 ms and 6.5 ms respectively for ResNet and ResNeXt,
      indicating that the deep learning framework has great potential for online fruit
      sorting. The results of this study demonstrate the potential of deep CNN
      application on analyzing the internal mechanical damage of fruit.

PMID- 29642453
TI  - Glycosylation of Hemagglutinin and Neuraminidase of Influenza A Virus as
      Signature for Ecological Spillover and Adaptation among Influenza Reservoirs.
AB  - Glycosylation of the hemagglutinin (HA) and neuraminidase (NA) of the influenza
      provides crucial means for immune evasion and viral fitness in a host population.
      However, the time-dependent dynamics of each glycosylation sites have not been
      addressed. We monitored the potential N-linked glycosylation (NLG) sites of over
      10,000 HA and NA of H1N1 subtype isolated from human, avian, and swine species
      over the past century. The results show a shift in glycosylation sites as a
      hallmark of 1918 and 2009 pandemics, and also for the 1976 "abortive pandemic".
      Co-segregation of particular glycosylation sites was identified as a
      characteristic of zoonotic transmission from animal reservoirs, and
      interestingly, of "reverse zoonosis" of human viruses into swine populations as
      well. After the 2009 pandemic, recent isolates accrued glycosylation at canonical
      sites in HA, reflecting gradual seasonal adaptation, and a novel glycosylation in
      NA as an independent signature for adaptation among humans. Structural
      predictions indicated a remarkably pleiotropic influence of glycans on multiple
      HA epitopes for immune evasion, without sacrificing the receptor binding of HA or
      the activity of NA. The results provided the rationale for establishing the
      ecological niche of influenza viruses among the reservoir and could be
      implemented for influenza surveillance and improving pandemic preparedness.

PMID- 29642455
TI  - Efficient Visible Light Communication Transmitters Based on Switching-Mode dc-dc
      Converters.
AB  - Visible light communication (VLC) based on solid-state lighting (SSL) is a
      promising option either to supplement or to substitute existing radio frequency
      (RF) wireless communication in indoor environments. VLC systems take advantage of
      the fast modulation of the visible light that light emitting diodes (LEDs)
      enable. The switching-mode dc-to-dc converter (SMCdc-dc) must be the cornerstone
      of the LED driver of VLC transmitters in order to incorporate the communication
      functionality into LED lighting, keeping high power efficiency. However, the new
      requirements related to the communication, especially the high bandwidth that the
      LED driver must achieve, converts the design of the SMCdc-dc into a very
      challenging task. In this work, three different methods for achieving such a high
      bandwidth with an SMCdc-dc are presented: increasing the order of the SMCdc-dc
      output filter, increasing the number of voltage inputs, and increasing the number
      of phases. These three strategies are combinable and the optimum design depends
      on the particular VLC application, which determines the requirements of the VLC
      transmitter. As an example, an experimental VLC transmitter based on a two-phase
      buck converter with a fourth-order output filter will demonstrate that a
      bandwidth of several hundred kilohertz (kHz) can be achieved with output power
      levels close to 10 W and power efficiencies between 85% and 90%. In conclusion,
      the design strategy presented allows us to incorporate VLC into SSL, achieving
      high bit rates without damaging the power efficiency of LED lighting.

PMID- 29642456
TI  - Crosslinked Polymer Ionic Liquid/Ionic Liquid Blends Prepared by
      Photopolymerization as Solid-State Electrolytes in Supercapacitors.
AB  - A photopolymerization method is used to prepare a mixture of polymer ionic liquid
      (PIL) and ionic liquid (IL). This mixture is used as a solid-state electrolyte in
      carbon nanoparticle (CNP)-based symmetric supercapacitors. The solid electrolyte
      is a binary mixture of a PIL and its corresponding IL. The PIL matrix is a cross
      linked polyelectrolyte with an imidazole salt cation coupled with two anions of
      Br- in PIL-M-(Br) and TFSI- in PIL-M-(TFSI), respectively. The corresponding
      ionic liquids have imidazolium salt cation coupled with two anions of Br- and
      TFSI-, respectively. This study investigates the electrochemical characteristics
      of PILs and their corresponding IL mixtures used as a solid electrolyte in
      supercapacitors. Results show that a specific capacitance, maximum power density
      and energy density of 87 and 58 F.g-1, 40 and 48 kW.kg-1, and 107 and 59.9 Wh.kg
      1 were achieved in supercapacitors based on (PIL-M-(Br)) and (PIL-M-(TFSI)) solid
      electrolytes, respectively.

PMID- 29642457
TI  - Dandelion Root Extract Induces Intracellular Ca2+ Increases in HEK293 Cells.
AB  - Dandelion (Taraxacum officinale Weber ex F.H.Wigg.) has been used for centuries
      as an ethnomedical remedy. Nonetheless, the extensive use of different kinds of
      dandelion extracts and preparations is based on empirical findings. Some of the
      tissue-specific effects reported for diverse dandelion extracts may result from
      their action on intracellular signaling cascades. Therefore, the aim of this
      study was to evaluate the effects of an ethanolic dandelion root extract (DRE) on
      Ca2+ signaling in human embryonic kidney (HEK) 293 cells. The cytotoxicity of
      increasing doses of crude DRE was determined by the Calcein viability assay. Fura
      2 and the fluorescence resonance energy transfer (FRET)-based probe ERD1 were
      used to measure cytoplasmic and intraluminal endoplasmic reticulum (ER) Ca2+
      levels, respectively. Furthermore, a green fluorescent protein (GFP)-based probe
      was used to monitor phospholipase C (PLC) activation (pleckstrin homology [PH]
      PLCdelta-GFP). DRE (10-400 ug/mL) exposure, in the presence of external Ca2+,
      dose-dependently increased intracellular Ca2+ levels. The DRE-induced Ca2+
      increase was significantly reduced in the absence of extracellular Ca2+. In
      addition, DRE caused a significant Ca2+ release from the ER of intact cells and a
      concomitant translocation of PH-PLCdelta-GFP. In conclusion, DRE directly
      activates both the release of Ca2+ from internal stores and a significant Ca2+
      influx at the plasma membrane. The resulting high Ca2+ levels within the cell
      seem to directly stimulate PLC activity.

PMID- 29642459
TI  - Bearing Fault Diagnosis by a Robust Higher-Order Super-Twisting Sliding Mode
      Observer.
AB  - An effective bearing fault detection and diagnosis (FDD) model is important for
      ensuring the normal and safe operation of machines. This paper presents a
      reliable model-reference observer technique for FDD based on modeling of a
      bearing's vibration data by analyzing the dynamic properties of the bearing and a
      higher-order super-twisting sliding mode observation (HOSTSMO) technique for
      making diagnostic decisions using these data models. The HOSTSMO technique can
      adaptively improve the performance of estimating nonlinear failures in rolling
      element bearings (REBs) over a linear approach by modeling 5 degrees of freedom
      under normal and faulty conditions. The effectiveness of the proposed technique
      is evaluated using a vibration dataset provided by Case Western Reserve
      University, which consists of vibration acceleration signals recorded for REBs
      with inner, outer, ball, and no faults, i.e., normal. Experimental results
      indicate that the proposed technique outperforms the ARX-Laguerre proportional
      integral observation (ALPIO) technique, yielding 18.82%, 16.825%, and 17.44%
      performance improvements for three levels of crack severity of 0.007, 0.014, and
      0.021 inches, respectively.

PMID- 29642458
TI  - Luminescent Lanthanide MOFs: A Unique Platform for Chemical Sensing.
AB  - In recent years, lanthanide metal-organic frameworks (LnMOFs) have developed to
      be an interesting subclass of MOFs. The combination of the characteristic
      luminescent properties of Ln ions with the intriguing topological structures of
      MOFs opens up promising possibilities for the design of LnMOF-based chemical
      sensors. In this review, we present the most recent developments of LnMOFs as
      chemical sensors by briefly introducing the general luminescence features of
      LnMOFs, followed by a comprehensive investigation of the applications of LnMOF
      sensors for cations, anions, small molecules, nitroaromatic explosives, gases,
      vapors, pH, and temperature, as well as biomolecules.

PMID- 29642460
TI  - Turning the Co-Production Corner: Methodological Reflections from an Action
      Research Project to Promote LGBT Inclusion in Care Homes for Older People.
AB  - : Background: Older lesbian, gay, bisexual and trans (LGBT) residents are often
      invisible in long-term care settings. This article presents findings from a
      community-based action research project, which attempted to address this
      invisibility through co-produced research with LGBT community members. Particular
      Question: What conditions enable co-produced research to emerge in long-term
      residential care settings for older people? Aims of Project: To analyse outcomes
      and challenges of action-oriented, co-produced research in the given context. In
      particular, we explore how co-production as a collaborative approach to action
      orientated research can emerge during the research/fieldwork process; and reflect
      critically on the ethics and effectiveness of this approach in advancing
      inclusion in context. METHODS: The project was implemented across six residential
      care homes in England. Reflections are based on qualitative evaluation data
      gathered pre- and post-project, which includes 37 interviews with care home
      staff, managers and community advisors (two of whom are co-authors). Results and
      Conclusions: We discuss how the co-production turn emerged during research and
      evaluate how the politics of this approach helped advance inclusion-itself
      crucial to well-being. We argue for the value of co-produced research in
      instigating organizational change in older people's care environments and of non
      didactic storytelling in LGBT awareness-raising amongst staff.

PMID- 29642461
TI  - German Public Support for Tobacco Control Policy Measures: Results from the
      German Study on Tobacco Use (DEBRA), a Representative National Survey.
AB  - Smoking prevalence in Germany remains high at approximately 28%. We assessed
      public support for tobacco legislation and associations between level of support
      and smoking and socio-demographic characteristics. Data from 2087 people were
      collected as part of the German Study on Tobacco Use ("DEBRA"): a nationally
      representative, face-to-face household survey. Public support was measured on
      total ban of sale, raising the minimum age for sales, taxation of tobacco
      industry sales, research into e-cigarettes, and ban of smoking in cars when
      children are present. Associations were assessed with multivariate logistic
      regression. Over 50% of the German population support taxing industry profits
      (57.3%) and assessing e-cigarettes as an aid to quit smoking (55.5%). Over 40%
      support raising the legal age of sale (43.1%), and 22.9% support a total ban on
      tobacco sales. A smoking ban in cars when children are present was most popular
      (71.5%), even among current smokers (67.0%). There is public support for stricter
      tobacco control measures in Germany. A smoking ban in cars when children are
      present could be a feasible policy to implement.

PMID- 29642463
TI  - Preparation of Ruthenium Dithiolene Complex/Polysiloxane Films and Their
      Responses to CO Gas.
AB  - To develop advanced materials using metal complexes, it is better to prepare
      metal complexes contained in composite or hybrid films. To achieve this purpose,
      we synthesized ruthenium complexes with dihalogen-substituted benzendithiolate
      ligands, [(eta6-C6Me6)Ru(S2C6H2X2)] (X = F, 3,6-Cl, Br, 4,5-Cl), 1b-1e. We also
      investigated preparation of 1c or 1e containing polysiloxane composite films and
      their reactivity to CO gas. All ruthenium complexes 1b-1e reacted with CO gas,
      and carbonyl ligand adducts 2b-2e were generated. Ruthenium complexes 1b-1e show
      two strong absorption peaks around 550 and 420 nm. After exposure to CO gas,
      these absorption peaks were immediately decreased without a peak shift. A similar
      trend was observed in 1c or 1e containing polysiloxane composite films. These
      results indicate that 1c and 1e were easily converted into 2c and 2e, both in the
      solution and the polysiloxane film during CO gas exposure.

PMID- 29642462
TI  - New Challenges in Targeting Signaling Pathways in Acute Lymphoblastic Leukemia by
      NGS Approaches: An Update.
AB  - The identification and study of genetic alterations involved in various signaling
      pathways associated with the pathogenesis of acute lymphoblastic leukemia (ALL)
      and the application of recent next-generation sequencing (NGS) in the
      identification of these lesions not only broaden our understanding of the
      involvement of various genetic alterations in the pathogenesis of the disease but
      also identify new therapeutic targets for future clinical trials. The present
      review describes the main deletions, amplifications, sequence mutations,
      epigenetic lesions, and new structural DNA rearrangements detected by NGS in B
      ALL and T-ALL and their clinical importance for therapeutic procedures. We
      reviewed the molecular basis of pathways including transcriptional regulation,
      lymphoid differentiation and development, TP53 and the cell cycle, RAS signaling,
      JAK/STAT, NOTCH, PI3K/AKT/mTOR, Wnt/beta-catenin signaling, chromatin structure
      modifiers, and epigenetic regulators. The implementation of NGS strategies has
      enabled important mutated genes in each pathway, their associations with the
      genetic subtypes of ALL, and their outcomes, which will be described further. We
      also discuss classic and new cryptic DNA rearrangements in ALL identified by mRNA
      seq strategies. Novel cooperative abnormalities in ALL could be key prognostic
      and/or predictive biomarkers for selecting the best frontline treatment and for
      developing therapies after the first relapse or refractory disease.

PMID- 29642464
TI  - Optimization of the Ultrasonic-Assisted Extraction of Phenolic Compounds from
      Oryza Sativa L. 'Violet Nori' and Determination of the Antioxidant Properties of
      its Caryopses and Leaves.
AB  - 'Violet Nori' is a new spontaneous growing violet rice variety showing a peculiar
      violet color in its fresh leaves as well. In this paper, the antioxidant
      properties and the content of total phenols, radical scavengers, and anthocyanins
      in 'Violet Nori' caryopses, flour, and leaves are explored and compared.
      Ultrasonic-Assisted Extraction (UAE) is employed for the extraction of phenolic
      compounds, improving the extraction conditions by Design of Experiments (DoE).
      The obtained results show that the Radical Scavenging Activities (RSAs), the
      Total Phenolic Contents (TPCs), and the anthocyanin amounts (1000-1500 MUg/g,
      expressed as cyanidin-3-glucoside) of 'Violet Nori' caryopses are higher than
      those in the other analyzed colored rice samples (300-900 MUg/g as cyanidin-3
      glucoside), with the exception of the cultivars 'Artemide' and 'Nerone', which
      show comparable values of RSAs and TPCs. The study of 'Violet Nori' leaves at
      different plant maturation stages shows that their anthocyanin content is 2-3
      times higher than in the caryopses and in the flour, reaching the highest levels
      at about 60 days from seeding. Thus, the estimated extraction yield of 4 kg
      anthocyanins/t makes fresh leaves very interesting for the extraction of
      anthocyanins on an industrial scale, whereas violet caryopses are a very
      interesting dietetic source of valuable anthocyanins and other antioxidant
      compounds.

PMID- 29642466
TI  - Non-Mutually Exclusive Deep Neural Network Classifier for Combined Modes of
      Bearing Fault Diagnosis.
AB  - The simultaneous occurrence of various types of defects in bearings makes their
      diagnosis more challenging owing to the resultant complexity of the constituent
      parts of the acoustic emission (AE) signals. To address this issue, a new
      approach is proposed in this paper for the detection of multiple combined faults
      in bearings. The proposed methodology uses a deep neural network (DNN)
      architecture to effectively diagnose the combined defects. The DNN structure is
      based on the stacked denoising autoencoder non-mutually exclusive classifier
      (NMEC) method for combined modes. The NMEC-DNN is trained using data for a single
      fault and it classifies both single faults and multiple combined faults. The
      results of experiments conducted on AE data collected through an experimental
      test-bed demonstrate that the DNN achieves good classification performance with a
      maximum accuracy of 95%. The proposed method is compared with a multi-class
      classifier based on support vector machines (SVMs). The NMEC-DNN yields better
      diagnostic performance in comparison to the multi-class classifier based on SVM.
      The NMEC-DNN reduces the number of necessary data collections and improves the
      bearing fault diagnosis performance.

PMID- 29642467
TI  - Proton Partial Breast Irradiation: Detailed Description of Acute Clinico
      Radiologic Effects.
AB  - Introduction: Accelerated partial breast irradiation (APBI) with protons results
      in a very different acute effect profile than standard whole breast irradiation.
      We reviewed our initial experience with proton APBI and felt that a detailed
      description of these effects were needed to permit a common tool to compare
      experience with this developing technology. Methods: Sixty sequential patients
      treated with proton APBI on a prospective protocol were evaluated and 43 patients
      with a minimum six-month follow-up underwent detailed photographic and radiologic
      analysis. The tumorectomy cavity plus an additional 1.5 cm clinical target volume
      (CTV) was treated with two or three passively-scattered proton beams to a dose of
      34 Gy in 10 fractions in one week. Photographs were taken at the end of
      radiation, at two weeks, six weeks, and every six months thereafter. Mammography
      was obtained at six months after radiation and annually thereafter. All visual
      changes were categorized using the smallest meaningful gradations in findings and
      are demonstrated herein. All treatment-related mammographic findings are
      reported. Findings: Visual and mammographic findings showed a clear time
      dependent relationship and significant variation between individuals. Peak skin
      reaction occurred at two to six weeks after completion of therapy. At two weeks
      most patients had either no visible effects and patchy erythema involving <50% of
      the treated skin (60%). At six weeks most patients had either patchy erythema
      involving <50% of the overlying skin (33%) or patchy erythema involving >50% of
      the treated skin (28%). Only one patient developed any moist desquamation. At six
      months most patients had no visible skin changes (57%) or a small, circular area
      of mild hyperpigmentation (33%). Mammographic changes seen at six months were
      regional skin thickening (40%), residual seroma (14%), localized retraction
      (26%), and fat necrosis (2%). A subcategorized variant on the CTCAE 4.0 was
      developed to foster granular recording of these findings.

PMID- 29642468
TI  - Study and Development of a Fluorescence Based Sensor System for Monitoring Oxygen
      in Wine Production: The WOW Project.
AB  - The importance of oxygen in the winemaking process is widely known, as it affects
      the chemical aspects and therefore the organoleptic characteristics of the final
      product. Hence, it is evident the usefulness of a continuous and real-time
      measurements of the levels of oxygen in the various stages of the winemaking
      process, both for monitoring and for control. The WOW project (Deployment of WSAN
      technology for monitoring Oxygen in Wine products) has focused on the design and
      the development of an innovative device for monitoring the oxygen levels in wine.
      This system is based on the use of an optical fiber to measure the luminescent
      lifetime variation of a reference metal/porphyrin complex, which decays in
      presence of oxygen. The developed technology results in a high sensitivity and
      low cost sensor head that can be employed for measuring the dissolved oxygen
      levels at several points inside a wine fermentation or aging tank. This system
      can be complemented with dynamic modeling techniques to provide predictive
      behavior of the nutrient evolution in space and time given few sampled measuring
      points, for both process monitoring and control purposes. The experimental
      validation of the technology has been first performed in a controlled laboratory
      setup to attain calibration and study sensitivity with respect to different photo
      luminescent compounds and alcoholic or non-alcoholic solutions, and then in an
      actual case study during a measurement campaign at a renown Italian winery.

PMID- 29642465
TI  - Translation and Translational Control in Dinoflagellates.
AB  - Dinoflagellates are unicellular protists that feature a multitude of unusual
      nuclear features, including large genomes, packaging of DNA without histones, and
      multiple gene copies organized as tandem gene arrays. Furthermore, all
      dinoflagellate mRNAs experience trans-splicing with a common 22-nucleotide splice
      leader (SL) sequence. These features challenge some of the concepts and
      assumptions about the regulation of gene expression derived from work on model
      eukaryotes such as yeasts and mammals. Translational control in the
      dinoflagellates, based on extensive study of circadian bioluminescence and by
      more recent microarray and transcriptome analyses, is now understood to be a
      crucial element in regulating gene expression. A picture of the translation
      machinery of dinoflagellates is emerging from the recent availability of
      transcriptomes of multiple dinoflagellate species and the first complete genome
      sequences. The components comprising the translational control toolkit of
      dinoflagellates are beginning to take shape and are outlined here.

PMID- 29642469
TI  - Flotillins Regulate Focal Adhesions by Interacting with alpha-Actinin and by
      Influencing the Activation of Focal Adhesion Kinase.
AB  - Cell-matrix adhesion and cell migration are physiologically important processes
      that also play a major role in cancer spreading. In cultured cells, matrix
      adhesion depends on integrin-containing contacts such as focal adhesions.
      Flotillin-1 and flotillin-2 are frequently overexpressed in cancers and are
      associated with poor survival. Our previous studies have revealed a role for
      flotillin-2 in cell-matrix adhesion and in the regulation of the actin
      cytoskeleton. We here show that flotillins are important for cell migration in a
      wound healing assay and influence the morphology and dynamics of focal adhesions.
      Furthermore, anchorage-independent growth in soft agar is enhanced by flotillins.
      In the absence of flotillins, especially flotillin-2, phosphorylation of focal
      adhesion kinase and extracellularly regulated kinase is diminished. Flotillins
      interact with alpha-actinin, a major regulator of focal adhesion dynamics. These
      findings are important for understanding the molecular mechanisms of how
      flotillin overexpression in cancers may affect cell migration and, especially,
      enhance metastasis formation.

PMID- 29642470
TI  - The Complete Chloroplast Genome of Heimia myrtifolia and Comparative Analysis
      within Myrtales.
AB  - Heimia myrtifolia is an important medicinal plant with several pharmacologically
      active alkaloids and is also used as an ornamental landscape plant. The purpose
      of this study is to complete and characterize the chloroplast (cp) genome of H.
      myrtifolia and compare genomic features to other Myrtales species' cp genomes.
      The analysis showed that H. myrtifolia has a total length of 159,219 bp with a
      typical quadripartite structure containing two identical inverted repeats (IRs)
      of 25,643 bp isolated by one large single copy (LSC) of 88,571 bp and one small
      single copy (SSC) of 18,822 bp. The H. myrtifolia cp genome contains 129 genes
      with eight ribosomal RNAs, 30 transfer RNAs, and 78 protein coding genes, in
      which 17 genes are duplicated in two IR regions. The genome organization
      including gene type and number and guanine-cytosine (GC) content is analyzed
      among the 12 cp genomes in this study. Approximately 255 simple sequence repeats
      (SSRs) and 16 forward, two reverses, and two palindromic repeats were identified
      in the H. myrtifolia cp genome. By comparing the whole H. myrtifolia cp genome
      with 11 other Myrtales species, the results showed that the sequence similarity
      was high between coding regions while sequence divergence was high between
      intergenic regions. By employing the full cp genomes for phylogenetic analysis,
      structural and sequence differences were characterized between H. myrtifolia and
      11 Myrtales species illustrating what patterns are common in the evolution of cp
      genomes within the Myrtales. The first entire cp genome in the genus Heimia
      provides a valuable resource for further studies in these medicinally and
      ornamentally important taxa.

PMID- 29642472
TI  - Reversible Redox Activity by Ion-pH Dually Modulated Duplex Formation of i-Motif
      DNA with Complementary G-DNA.
AB  - The unique biological features of supramolecular DNA have led to an increasing
      interest in biomedical applications such as biosensors. We have developed an i
      motif and G-rich DNA conjugated single-walled carbon nanotube hybrid materials,
      which shows reversible conformational switching upon external stimuli such as pH
      (5 and 8) and presence of ions (Li+ and K+). We observed reversible
      electrochemical redox activity upon external stimuli in a quick and robust
      manner. Given the ease and the robustness of this method, we believe that pH- and
      ion-driven reversible DNA structure transformations will be utilized for future
      applications for developing novel biosensors.

PMID- 29642471
TI  - Relationship between the Manner of Mobile Phone Use and Depression, Anxiety, and
      Stress in University Students.
AB  - Objectives: There is insufficient evidence regarding the potential risk of mobile
      phone use on mental health. Therefore, the aim of this research was to examine
      the relationship between mobile phone use and mental health by measuring the
      levels of depression, anxiety, and stress among university students in Serbia and
      Italy. Methods: This cross-sectional study was carried out at two distinguished
      universities in Serbia and Italy from March to May of the 2015/2016 academic year
      and included 785 students of both genders. The questionnaire was compiled and
      developed from different published sources regarding the manner and intensity of
      mobile phone use, along with the Depression Anxiety Stress Scale (DASS 42) for
      measuring psychological health. The statistical analysis of the data included the
      application of binary logistic regression and correlation tests. Results:
      Statistical analysis indicates that anxiety symptoms are somewhat more present in
      younger students (odds ratio (OR) = 0.86, 95% confidence interval (CI): 0.76
      0.96), in those who send more text messages SMSs (OR = 1.15, 95% CI: 1.11-1.31),
      and in those who browse the internet less frequently (OR = 0.84, 95% CI: 0.73
      0.95). Stress is more common in students who make fewer calls a day (OR = 0.79,
      95% CI: 0.64-0.97), as well in those who spend more time talking on the mobile
      phone per day (OR = 1.28, 95% CI: 1.12-1.56). The strongest predictor of high
      stress levels was keeping the mobile phone less than 1 m away during sleeping (OR
      = 1.48, 95% CI: 1.12-2.08). Conclusions: The results indicated that the intensity
      and modality of mobile phone use could be a factor that can influence causal
      pathways leading to mental health problems in the university student population.

PMID- 29642473
TI  - Resistance to Carbapenems in Non-Typhoidal Salmonella enterica Serovars from
      Humans, Animals and Food.
AB  - Non-typhoidal serovars of Salmonella enterica (NTS) are a leading cause of food
      borne disease in animals and humans worldwide. Like other zoonotic bacteria, NTS
      have the potential to act as reservoirs and vehicles for the transmission of
      antimicrobial drug resistance in different settings. Of particular concern is the
      resistance to critical "last resort" antimicrobials, such as carbapenems. In
      contrast to other Enterobacteriaceae (e.g., Klebsiella pneumoniae, Escherichia
      coli, and Enterobacter, which are major nosocomial pathogens affecting
      debilitated and immunocompromised patients), carbapenem resistance is still very
      rare in NTS. Nevertheless, it has already been detected in isolates recovered
      from humans, companion animals, livestock, wild animals, and food. Five
      carbapenemases with major clinical importance-namely KPC (Klebsiella pneumoniae
      carbapenemase) (class A), IMP (imipenemase), NDM (New Delhi metallo-beta
      lactamase), VIM (Verona integron-encoded metallo-beta-lactamase) (class B), and
      OXA-48 (oxacillinase, class D)-have been reported in NTS. Carbapenem resistance
      due to the production of extended spectrum- or AmpC beta-lactamases combined with
      porin loss has also been detected in NTS. Horizontal gene transfer of
      carbapenemase-encoding genes (which are frequently located on self-transferable
      plasmids), together with co- and cross-selective adaptations, could have been
      involved in the development of carbapenem resistance by NTS. Once acquired by a
      zoonotic bacterium, resistance can be transmitted from humans to animals and from
      animals to humans through the food chain. Continuous surveillance of resistance
      to these "last resort" antibiotics is required to establish possible links
      between reservoirs and to limit the bidirectional transfer of the encoding genes
      between S. enterica and other commensal or pathogenic bacteria.

PMID- 29642474
TI  - Effects of Co-Processing Sewage Sludge in the Cement Kiln on PAHs, Heavy Metals
      Emissions and the Surrounding Environment.
AB  - To understand the effects of co-processing sewage sludge in the cement kiln on
      non-criterion pollutants emissions and its surrounding environment, the flue gas
      from a cement kiln stack, ambient air and soil from the background/downwind sites
      were collected in the cement plant. Polycyclic aromatic hydrocarbons (PAHs) and
      heavy metals of the samples were analyzed. The results show that PAHs in flue gas
      mainly exist in the gas phase and the low molecular weight PAHs are the
      predominant congener. The co-processing sewage sludge results in the increase in
      PAHs and heavy metals emissions, especially high molecular weight PAHs and low
      volatile heavy metals such as Cd and Pb in the particle phase, while it does not
      change their compositions and distribution patterns significantly. The
      concentrations and their distributions of the PAHs and heavy metals between the
      emissions and ambient air have a positive correlation and the co-processing
      sewage sludge results in the increase of PAHs and heavy metals concentrations in
      the ambient air. The PAHs concentration level and their distribution in soil are
      proportional to those in the particle phase of flue gas, and the co-processing
      sewage sludge can accelerate the accumulation of the PAHs and heavy metals in the
      surrounding soil, especially high/middle molecular weight PAHs and low-volatile
      heavy metals.

PMID- 29642475
TI  - Our Evolving Understanding of the Mechanism of Quinolones.
AB  - The maintenance of DNA supercoiling is essential for the proper regulation of a
      plethora of biological processes. As a consequence of this mode of regulation,
      ahead of the replication fork, DNA replication machinery is prone to introducing
      supercoiled regions into the DNA double helix. Resolution of DNA supercoiling is
      essential to maintain DNA replication rates that are amenable to life. This
      resolution is handled by evolutionarily conserved enzymes known as
      topoisomerases. The activity of topoisomerases is essential, and therefore
      constitutes a prime candidate for targeting by antibiotics. In this review, we
      present hallmark investigations describing the mode of action of quinolones, one
      of the antibacterial classes targeting the function of topoisomerases in
      bacteria. By chronologically analyzing data gathered on the mode of action of
      this imperative antibiotic class, we highlight the necessity to look beyond
      primary drug-target interactions towards thoroughly understanding the mechanism
      of quinolones at the level of the cell.

PMID- 29642476
TI  - Tailoring of Perpendicular Magnetic Anisotropy in Dy13Fe87 Thin Films with
      Hexagonal Antidot Lattice Nanostructure.
AB  - In this article, the magnetic properties of hexagonally ordered antidot arrays
      made of Dy13Fe87 alloy are studied and compared with corresponding ones of
      continuous thin films with the same compositions and thicknesses, varying between
      20 nm and 50 nm. Both samples, the continuous thin films and antidot arrays, were
      prepared by high vacuum e-beam evaporation of the alloy on the top-surface of
      glass and hexagonally self-ordered nanoporous alumina templates, which serve as
      substrates, respectively. By using a highly sensitive magneto-optical Kerr effect
      (MOKE) and vibrating sample magnetometer (VSM) measurements an interesting
      phenomenon has been observed, consisting in the easy magnetization axis transfer
      from a purely in-plane (INP) magnetic anisotropy to out-of-plane (OOP)
      magnetization. For the 30 nm film thickness we have measured the volume
      hysteresis loops by VSM with the easy magnetization axis lying along the OOP
      direction. Using magnetic force microscopy measurements (MFM), there is strong
      evidence to suggest that the formation of magnetic domains with OOP magnetization
      occurs in this sample. This phenomenon can be of high interest for the
      development of novel magnetic and magneto-optic perpendicular recording patterned
      media based on template-assisted deposition techniques.

PMID- 29642477
TI  - 3D Copper Foam-Supported CuCo2O4 Nanosheet Arrays as Electrode for Enhanced Non
      Enzymatic Glucose Sensing.
AB  - CuCo2O4 anchored on Cu foam (CuCo2O4/CF) with polycrystalline features was
      fabricated by a mild process based on solvothermal reaction and subsequent
      calcination in this work. The structure and morphology of the obtained materials
      were thoroughly characterized by X-ray diffraction, X-ray photoelectron
      spectroscopy, field-emission scanning electron microscopy, and transmission
      electron microscopy. According to the above analysis, the morphology of the
      CuCo2O4 was nanosheet arrays. Meanwhile, the CuCo2O4 was grown on Cu foam
      successfully. The CuCo2O4/CF displayed good electrochemical properties for
      glucose detection at a linear range from 0 mM to 1.0 mM. Meanwhile, the detection
      limit was as low as 1 MUM (S/N = 3), and the sensitivity was 20,981 MUA.mM-1.cm
      2. Moreover, the selectivity and the stability were tested with excellent
      results. This nanomaterial could show great potential application in
      electrochemical sensors.

PMID- 29642478
TI  - Diagnostic Criteria and Clinical Outcomes in Sarcopenia Research: A Literature
      Review.
AB  - By the sixth decade of life, nearly one quarter of the population has substantial
      muscle atrophy, or sarcopenia. Despite the creation of a standardized definition
      of sarcopenia by the European Working Group on Sarcopenia in Older People,
      variability may exist in the diagnostic criteria utilized for clinical sarcopenia
      research. The primary objectives of this review were to characterize diagnostic
      criteria used for measurement of sarcopenia in original studies, and to describe
      associations between sarcopenia and important clinical outcomes. We performed a
      literature review of the term "sarcopenia" in PubMed. Inclusion criteria were
      English language, original data, a clear and specific definition for diagnosing
      sarcopenia, and the analysis of sarcopenia's effect on a clinical outcome. A
      total of 283 studies met inclusion criteria. More than half of the included
      sarcopenia investigations were level IV studies (54.1%), while 43.1% provided
      level II evidence. Under one third (27.6%) of studies examined sarcopenia with
      regard to surgical outcomes. In terms of diagnostic criteria for sarcopenia, 264
      (93.3%) studies used measures of skeletal muscle mass, with dual energy X-ray
      absorptiometry (DEXA) being the most common modality (43.6%). Sarcopenia was
      found to be a consistent predictor of chronic disease progression, all-cause
      mortality, poorer functional outcomes, and postoperative complications. In
      conclusion, there is substantial evidence that sarcopenia impacts both medical
      and surgical outcomes. However, current research has utilized heterogeneous
      diagnostic criteria for sarcopenia. Further efforts to standardize the modalities
      used to diagnose sarcopenia in clinical research and practice will help
      strengthen our ability to study this important phenomenon.

PMID- 29642479
TI  - Real-Time Seismic Data from the Bottom Sea.
AB  - An anchored marine seismometer, acquiring real-time seismic data, has been built
      and tested. The system consists of an underwater seismometer, a surface buoy, and
      a mooring line that connects them. Inductive communication through the mooring
      line provides an inexpensive, reliable, and flexible solution. Prior to the
      deployment the dynamics of the system have been simulated numerically in order to
      find optimal materials, cables, buoys, and connections under critical marine
      conditions. The seismometer used is a high sensitivity triaxial broadband
      geophone able to measure low vibrational signals produced by the underwater
      seismic events. The power to operate the surface buoy is provided by solar
      panels. Additional batteries are needed for the underwater unit. In this paper we
      also present the first results and an earthquake detection of a prototype system
      that demonstrates the feasibility of this concept. The seismometer transmits
      continuous data at a rate of 1000 bps to a controller equipped with a radio link
      in the surface buoy. A GPS receiver on the surface buoy has been configured to
      perform accurate timestamps on the seismic data, which makes it possible to
      integrate the seismic data from these marine seismometers into the existing
      seismic network.

PMID- 29642480
TI  - Examining Youth Dual and Polytobacco Use with E-Cigarettes.
AB  - E-cigarettes and other non-cigarette tobacco products are increasingly popular
      among youth. Little is known to inform public health efforts to reduce youth use.
      We examined psychosocial correlates of single and multiple tobacco product use
      among youth e-cigarette users. Data were from the 2014 Florida Youth Tobacco
      Survey (N = 69,923), a representative sample of Florida middle and high school
      students. Associations between combinations of e-cigarette, cigarette and other
      tobacco product (OTP) use and psychosocial variables were examined using
      multinomial logistic regression with an analytic sample of N = 2756. Most e
      cigarette-using youth used at least one other product (81%). Perceiving
      cigarettes as easy to quit was significantly associated with greater likelihood
      of combined e-cigarette/OTP use (relative risk ratio (RRR) = 2.51, p < 0.001) and
      combined e-cigarette/cigarette/OTP use (RRR = 3.20, p < 0.0001). Thinking you
      will be smoking cigarettes in 5 years was associated with product combinations
      that include cigarettes. Tobacco company marketing receptivity was associated
      with multiple product user types. Given that specific psychosocial factors put
      youth at risk for concurrent use of e-cigarettes with tobacco products, public
      health efforts should address polytobacco use specifically, instead of individual
      product use. Youth perceptions about the ease of quitting cigarettes, intentions
      to continue smoking cigarettes and receptivity to tobacco company marketing are
      promising areas for messaging aimed at reducing e-cigarette polytobacco product
      use.

PMID- 29642481
TI  - 3,3'-Bicarbazole-Based Host Molecules for Solution-Processed Phosphorescent
      OLEDs.
AB  - Solution-processed organic light-emitting diodes (OLEDs) are attractive due to
      their low-cost, large area displays, and lighting features. Small molecules as
      well as polymers can be used as host materials within the solution-processed
      emitting layer. Herein, we report two 3,3'-bicarbazole-based host small
      molecules, which possess a structural isomer relationship. 9,9'-Di-4-n
      butylphenyl-9H,9'H-3,3'-bicarbazole (BCz-nBuPh) and 9,9'-di-4-t-butylphenyl
      9H,9'H-3,3'-bicarbazole (BCz-tBuPh) exhibited similar optical properties within
      solutions but different photoluminescence within films. A solution-processed
      green phosphorescent OLED with the BCz-tBuPh host exhibited a high maximum
      current efficiency and power efficiency of 43.1 cd/A and 40.0 lm/W, respectively,
      compared to the device with the BCz-nBuPh host.

PMID- 29642482
TI  - Extracellular Phytase Production by the Wine Yeast S. cerevisiae (Finarome
      Strain) during Submerged Fermentation.
AB  - One of the key steps in the production of phytases of microbial origin is
      selection of culture parameters, followed by isolation of the enzyme and
      evaluation of its catalytic activity. It was found that conditions for S.
      cerevisiae yeast culture, strain Finarome, giving the reduction in phytic acid
      concentration of more than 98% within 24 h of incubation were as follows: pH 5.5,
      32  degrees C, continuous stirring at 80 rpm, the use of mannose as a carbon
      source and aspartic acid as a source of nitrogen. The highest catalytic activity
      of the isolated phytase was observed at 37  degrees C, pH 4.0 and using phytate
      as substrate at concentration of 5.0 mM. The presence of ethanol in the medium at
      a concentration of 12% v/v reduces the catalytic activity to above 60%.
      Properties of phytase derived from S. cerevisiae yeast culture, strain Finarome,
      indicate the possibility of its application in the form of a cell's free crude
      protein isolate for the hydrolysis of phytic acid to improve the efficiency of
      alcoholic fermentation processes. Our results also suggest a possibility to use
      the strain under study to obtain a fusant derived with specialized distillery
      strains, capable of carrying out a highly efficient fermentation process combined
      with the utilization of phytates.

PMID- 29642483
TI  - Drawing Inspiration from Human Brain Networks: Construction of Interconnected
      Virtual Networks.
AB  - Virtualization of wireless sensor networks (WSN) is widely considered as a
      foundational block of edge/fog computing, which is a key technology that can help
      realize next-generation Internet of things (IoT) networks. In such scenarios,
      multiple IoT devices and service modules will be virtually deployed and
      interconnected over the Internet. Moreover, application services are expected to
      be more sophisticated and complex, thereby increasing the number of modifications
      required for the construction of network topologies. Therefore, it is imperative
      to establish a method for constructing a virtualized WSN (VWSN) topology that
      achieves low latency on information transmission and high resilience against
      network failures, while keeping the topological construction cost low. In this
      study, we draw inspiration from inter-modular connectivity in human brain
      networks, which achieves high performance when dealing with large-scale networks
      composed of a large number of modules (i.e., regions) and nodes (i.e., neurons).
      We propose a method for assigning inter-modular links based on a connectivity
      model observed in the cerebral cortex of the brain, known as the exponential
      distance rule (EDR) model. We then choose endpoint nodes of these links by
      controlling inter-modular assortativity, which characterizes the topological
      connectivity of brain networks. We test our proposed methods using simulation
      experiments. The results show that the proposed method based on the EDR model can
      construct a VWSN topology with an optimal combination of communication
      efficiency, robustness, and construction cost. Regarding the selection of
      endpoint nodes for the inter-modular links, the results also show that high
      assortativity enhances the robustness and communication efficiency because of the
      existence of inter-modular links of two high-degree nodes.

PMID- 29642485
TI  - Differential Diagnosis of Autism Spectrum Disorder and Post Traumatic Stress
      Disorder: Two Clinical Cases.
AB  - Autism spectrum disorder (ASD) is estimated to affect one in 68 children. Given
      the increase in both prevalence and awareness of ASD, it is critical to provide
      accurate and timely diagnosis. However, ASD often co-occurs with other disorders,
      making diagnosis difficult. The objective of the current case study was to
      provide two examples of differential diagnosis in ASD and post-traumatic stress
      disorder (PTSD) observed in an autism clinic. In both cases, the goal was to
      decide whether each child should be given a diagnosis of ASD, PTSD, or both.

PMID- 29642484
TI  - Differential Expression and Clinical Significance of Transforming Growth Factor
      Beta Isoforms in GBM Tumors.
AB  - Glioblastoma (GBM) represents the most common and aggressive malignant primary
      brain tumors in adults. Response to standard treatment is transitory and the
      survival of clinical trial cohorts are little more than 14 months. GBM are
      characterized by excessive proliferation, invasiveness, and radio
      /chemoresistance features; which are strongly upregulated by transforming growth
      factor-beta (TGF-beta). We hypothesized that TGF-beta gene expression could
      correlate with overall survival (OS) and serve as a prognostic biomarker. TGF
      beta1 and -beta2 expression were analyzed by qPCR in 159 GBM tumor specimens.
      Kaplan-Meier and multivariate analyses were used to correlate expression with OS
      and progression-free survival (PFS). In GBM, TGF-beta1 and -beta2 levels were 33-
      and 11-fold higher respectively than in non-tumoral samples. Kaplan-Meier and
      multivariate analyses revealed that high to moderate expressions of TGF-beta1
      significantly conferred a strikingly poorer OS and PFS in newly diagnosed
      patients. Interestingly, at relapse, neither isoforms had meaningful impact on
      clinical evolution. We demonstrate that TGF-beta1 is the dominant isoform in
      newly diagnosed GBM rather than the previously acknowledged TGF-beta2. We believe
      our study is the first to unveil a significant relationship between TGF-beta1
      expression and OS or PFS in newly diagnosed GBM. TGF-beta1 could serve as a
      prognostic biomarker or target affecting treatment planning and patient follow
      up.

PMID- 29642486
TI  - Hybrid Drug Delivery Patches Based on Spherical Cellulose Nanocrystals and
      Colloid Titania-Synthesis and Antibacterial Properties.
AB  - Spherical cellulose nanocrystal-based hybrids grafted with titania nanoparticles
      were successfully produced for topical drug delivery. The conventional analytical
      filter paper was used as a precursor material for cellulose nanocrystals (CNC)
      production. Cellulose nanocrystals were extracted via a simple and quick two-step
      process based on first the complexation with Cu(II) solution in aqueous ammonia
      followed by acid hydrolysis with diluted H2SO4. Triclosan was selected as a model
      drug for complexation with titania and further introduction into the
      nanocellulose based composite. Obtained materials were characterized by a broad
      variety of microscopic, spectroscopic, and thermal analysis methods. The drug
      release studies showed long-term release profiles of triclosan from the titania
      based nanocomposite that agreed with Higuchi model. The bacterial susceptibility
      tests demonstrated that released triclosan retained its antibacterial activity
      against Escherichia coli and Staphylococcus aureus. It was found that a small
      amount of titania significantly improved the antibacterial activity of obtained
      nanocomposites, even without immobilization of model drug. Thus, the developed
      hybrid patches are highly promising candidates for potential application as
      antibacterial agents.

PMID- 29642487
TI  - Semaphorin 3C and Its Receptors in Cancer and Cancer Stem-Like Cells.
AB  - Neurodevelopmental programs are frequently dysregulated in cancer. Semaphorins
      are a large family of guidance cues that direct neuronal network formation and
      are also implicated in cancer. Semaphorins have two kinds of receptors,
      neuropilins and plexins. Besides their role in development, semaphorin signaling
      may promote or suppress tumors depending on their context. Sema3C is a secreted
      semaphorin that plays an important role in the maintenance of cancer stem-like
      cells, promotes migration and invasion, and may facilitate angiogenesis.
      Therapeutic strategies that inhibit Sema3C signaling may improve cancer control.
      This review will summarize the current research on the Sema3C pathway and its
      potential as a therapeutic target.

PMID- 29642488
TI  - Sinularin Selectively Kills Breast Cancer Cells Showing G2/M Arrest, Apoptosis,
      and Oxidative DNA Damage.
AB  - The natural compound sinularin, isolated from marine soft corals, is
      antiproliferative against several cancers, but its possible selective killing
      effect has rarely been investigated. This study investigates the selective
      killing potential and mechanisms of sinularin-treated breast cancer cells. In 3
      (4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-
      tetrazolium, inner salt (MTS) assay, sinularin dose-responsively decreased the
      cell viability of two breast cancer (SKBR3 and MDA-MB-231) cells, but showed less
      effect on breast normal (M10) cells after a 24 h treatment. According to 7
      aminoactinomycin D (7AAD) flow cytometry, sinularin dose-responsively induced the
      G2/M cycle arrest of SKBR3 cells. Sinularin dose-responsively induced apoptosis
      on SKBR3 cells in terms of a flow cytometry-based annexin V/7AAD assay and
      pancaspase activity, as well as Western blotting for cleaved forms of poly(ADP
      ribose) polymerase (PARP), caspases 3, 8, and 9. These caspases and PARP
      activations were suppressed by N-acetylcysteine (NAC) pretreatment. Moreover,
      sinularin dose-responsively induced oxidative stress and DNA damage according to
      flow cytometry analyses of reactive oxygen species (ROS), mitochondrial membrane
      potential (MitoMP), mitochondrial superoxide, and 8-oxo-2'-deoxyguanosine (8
      oxodG)). In conclusion, sinularin induces selective killing, G2/M arrest,
      apoptosis, and oxidative DNA damage of breast cancer cells.

PMID- 29642489
TI  - Click Access to a Cyclodextrin-Based Spatially Confined AIE Material for
      Hydrogenase Recognition.
AB  - The spatial confinement of conjugated phenyl rotators is a compulsory requirement
      for the fluorescence enhancement of aggregation induced emission (AIE) molecules.
      This work reports a novel spatially confined AIE material by restricting several
      tetraphenylethylene (TPE) molecules around the primary face of beta-cyclodextrin
      (CD) via a Cu(I) catalytic 1,3-dipolar cycloaddition reaction (click chemistry).
      The spatial confinement effect was found to significantly enhance the
      fluorescence emission when compared with a single TPE modified CD. In addition,
      the emission maxima took place with the dimethyl sulfoxide volume ratio of 30% in
      a water mixture, which is remarkably different from traditional AIE molecules.
      Benefiting from the CD's complexation effect, this material exhibits a selective
      fluorescence quenching property in certain hydrogenases and can be used as a
      fluorescence probe for hydrogenase sensing. This demonstrates the potential of
      the spatially confined AIECD for practical applications.

PMID- 29642490
TI  - Experimental Analysis of Critical Current and Alternating Current Losses of High
      Temperature Superconductor Tape with Resin and Gallium-Indium-Tin.
AB  - This paper experimentally analyzes the critical current degradation and AC
      (alternating current) losses of second-generation (2G) high-temperature
      superconductor (HTS) tape during the impregnation process. Two impregnation
      materials were utilized: Gallium-Indium-Tin (GaInSn), and an epoxy resin,
      Araldite. The critical current of the impregnation materials was measured after
      different thermal cycles and compared with the tape with no impregnation process.
      The experimental results show that the critical current of Yttrium Barium Copper
      Oxide (YBCO) short samples varies between differently impregnated materials. The
      resin, Araldite, degraded the critical current; however, the GaInSn showed no
      degradation. Two degradation patterns with Araldite were identified due to the
      impregnation process, and the corresponding causes were analyzed. We further
      measured the AC losses of tapes impregnated with liquid metal at different
      frequencies, up to 600 Hz. Based on the experimental results, GaInSn liquid metal
      should be the most suitable impregnation material in terms of critical current
      degradation.

PMID- 29642491
TI  - Defocus Blur Detection and Estimation from Imaging Sensors.
AB  - Sparse representation has been proven to be a very effective technique for
      various image restoration applications. In this paper, an improved sparse
      representation based method is proposed to detect and estimate defocus blur of
      imaging sensors. Considering the fact that the patterns usually vary remarkably
      across different images or different patches in a single image, it is unstable
      and time-consuming for sparse representation over an over-complete dictionary. We
      propose an adaptive domain selection scheme to prelearn a set of compact
      dictionaries and adaptively select the optimal dictionary to each image patch.
      Then, with nonlocal structure similarity, the proposed method learns nonzero-mean
      coefficients' distributions that are much more closer to the real ones. More
      accurate sparse coefficients can be obtained and further improve the performance
      of results. Experimental results validate that the proposed method outperforms
      existing defocus blur estimation approaches, both qualitatively and
      quantitatively.

PMID- 29642492
TI  - Effects of Intragastric Administration of Tryptophan on the Blood Glucose
      Response to a Nutrient Drink and Energy Intake, in Lean and Obese Men.
AB  - Tryptophan stimulates plasma cholecystokinin and pyloric pressures, both of which
      slow gastric emptying. Gastric emptying regulates postprandial blood glucose.
      Tryptophan has been reported to decrease energy intake. We investigated the
      effects of intragastric tryptophan on the glycaemic response to, and gastric
      emptying of, a mixed-nutrient drink, and subsequent energy intake. Lean and obese
      participants (n = 16 each) received intragastric infusions of 1.5 g ("Trp-1.5g")
      or 3.0 g ("Trp-3.0g") tryptophan, or control, and 15 min later consumed a mixed
      nutrient drink (56 g carbohydrates). Gastric emptying (13C-acetate breath-test),
      blood glucose, plasma C-peptide, glucagon, cholecystokinin and tryptophan
      concentrations were measured (t = 0-60 min). Energy intake was assessed between t
      = 60-90 min. In lean individuals, Trp-3.0g, but not Trp-1.5g, slowed gastric
      emptying, reduced C-peptideAUC and increased glucagonAUC (all P < 0.05), but did
      not significantly decrease the blood glucose response to the drink, stimulate
      cholecystokinin or reduce mean energy intake, compared with control. In obese
      individuals, Trp-3.0g, but not Trp-1.5g, tended to slow gastric emptying (P =
      0.091), did not affect C-peptideAUC, increased glucagonAUC (P < 0.001) and
      lowered blood glucose at t = 30 min (P < 0.05), and did not affect
      cholecystokinin or mean energy intake. In obese individuals, intragastrically
      administered tryptophan may reduce postprandial blood glucose by slowing gastric
      emptying; the lack of effect on mean energy intake requires further
      investigation.

PMID- 29642493
TI  - Effects of tDCS on Real-Time BCI Detection of Pedaling Motor Imagery.
AB  - The purpose of this work is to strengthen the cortical excitability over the
      primary motor cortex (M1) and the cerebro-cerebellar pathway by means of a new
      transcranial direct current stimulation (tDCS) configuration to detect lower limb
      motor imagery (MI) in real time using two different cognitive neural states:
      relax and pedaling MI. The anode is located over the primary motor cortex in Cz,
      and the cathode over the right cerebro-cerebellum. The real-time brain-computer
      interface (BCI) designed is based on finding, for each electrode selected, the
      power at the particular frequency where the most difference between the two
      mental tasks is observed. Electroencephalographic (EEG) electrodes are placed
      over the brain's premotor area (PM), M1, supplementary motor area (SMA) and
      primary somatosensory cortex (S1). A single-blind study is carried out, where
      fourteen healthy subjects are separated into two groups: sham and active tDCS.
      Each subject is experimented on for five consecutive days. On all days, the
      results achieved by the active tDCS group were over 60% in real-time detection
      accuracy, with a five-day average of 62.6%. The sham group eventually reached
      those levels of accuracy, but it needed three days of training to do so.

PMID- 29642494
TI  - Raman Spectroscopic and Microscopic Analysis for Monitoring Renal Osteodystrophy
      Signatures.
AB  - Defining the pathogenesis of renal osteodystrophy (ROD) and its treatment
      efficacy are difficult, since many factors potentially affect bone quality. In
      this study, confocal Raman microscopy and parallel statistical analysis were used
      to identify differences in bone composition between healthy and ROD bone tissues
      through direct visualization of three main compositional parametric ratios,
      namely, calcium content, mineral-to-matrix, and carbonate-to-matrix. Besides the
      substantially lower values found in ROD specimens for these representative
      ratios, an obvious accumulation of phenylalanine is Raman spectroscopically
      observed for the first time in ROD samples and reported here. Thus, elevated
      phenylalanine could also be considered as an indicator of the disease. Since the
      image results are based on tens of thousands of spectra per sample, not only are
      the average ratios statistically significantly different for normal and ROD bone,
      but the method is clearly powerful in distinguishing between the two types of
      samples. Furthermore, the statistical outcomes demonstrate that only a relatively
      small number of spectra need to be recorded in order to classify the samples.
      This work thus opens the possibility of future development of in vivo Raman
      sensors for assessment of bone structure, remodeling, and mineralization, where
      different biomarkers are simultaneously detected with unprecedented accuracy.

PMID- 29642495
TI  - Visual Servoing-Based Nanorobotic System for Automated Electrical
      Characterization of Nanotubes inside SEM.
AB  - The maneuvering and electrical characterization of nanotubes inside a scanning
      electron microscope (SEM) has historically been time-consuming and laborious for
      operators. Before the development of automated nanomanipulation-enabled
      techniques for the performance of pick-and-place and characterization of
      nanoobjects, these functions were still incomplete and largely operated manually.
      In this paper, a dual-probe nanomanipulation system vision-based feedback was
      demonstrated to automatically perform 3D nanomanipulation tasks, to investigate
      the electrical characterization of nanotubes. The XY-position of Atomic Force
      Microscope (AFM) cantilevers and individual carbon nanotubes (CNTs) were
      precisely recognized via a series of image processing operations. A coarse-to
      fine positioning strategy in the Z-direction was applied through the combination
      of the sharpness-based depth estimation method and the contact-detection method.
      The use of nanorobotic magnification-regulated speed aided in improving working
      efficiency and reliability. Additionally, we proposed automated alignment of
      manipulator axes by visual tracking the movement trajectory of the end effector.
      The experimental results indicate the system's capability for automated
      measurement electrical characterization of CNTs. Furthermore, the automated
      nanomanipulation system has the potential to be extended to other
      nanomanipulation tasks.

PMID- 29642496
TI  - DCT-Based Preprocessing Approach for ICA in Hyperspectral Data Analysis.
AB  - The huge quantity of information and the high spectral resolution of
      hyperspectral imagery present a challenge when performing traditional processing
      techniques such as classification. Dimensionality and noise reduction improves
      both efficiency and accuracy, while retaining essential information. Among the
      many dimensionality reduction methods, Independent Component Analysis (ICA) is
      one of the most popular techniques. However, ICA is computationally costly, and
      given the absence of specific criteria for component selection, constrains its
      application in high-dimension data analysis. To overcome this limitation, we
      propose a novel approach that applies Discrete Cosine Transform (DCT) as
      preprocessing for ICA. Our method exploits the unique capacity of DCT to pack
      signal energy in few low-frequency coefficients, thus reducing noise and
      computation time. Subsequently, ICA is applied on this reduced data to make the
      output components as independent as possible for subsequent hyperspectral
      classification. To evaluate this novel approach, the reduced data using (1) ICA
      without preprocessing; (2) ICA with the commonly used preprocessing techniques
      which is Principal Component Analysis (PCA); and (3) ICA with DCT preprocessing
      are tested with Support Vector Machine (SVM) and K-Nearest Neighbor (K-NN)
      classifiers on two real hyperspectral datasets. Experimental results in both
      instances indicate that data after our proposed DCT preprocessing method combined
      with ICA yields superior hyperspectral classification accuracy.

PMID- 29642497
TI  - Computational Modelling of Large Scale Phage Production Using a Two-Stage Batch
      Process.
AB  - Cost effective and scalable methods for phage production are required to meet an
      increasing demand for phage, as an alternative to antibiotics. Computational
      models can assist the optimization of such production processes. A model is
      developed here that can simulate the dynamics of phage population growth and
      production in a two-stage, self-cycling process. The model incorporates variable
      infection parameters as a function of bacterial growth rate and employs ordinary
      differential equations, allowing application to a setup with multiple reactors.
      The model provides simple cost estimates as a function of key operational
      parameters including substrate concentration, feed volume and cycling times. For
      the phage and bacteria pairing examined, costs and productivity varied by three
      orders of magnitude, with the lowest cost found to be most sensitive to the
      influent substrate concentration and low level setting in the first vessel. An
      example case study of phage production is also presented, showing how parameter
      values affect the production costs and estimating production times. The approach
      presented is flexible and can be used to optimize phage production at laboratory
      or factory scale by minimizing costs or maximizing productivity.

PMID- 29642498
TI  - Monitoring of the Apple Fruit Moth: Detection of Genetic Variation and Structure
      Applying a Novel Multiplex Set of 19 STR Markers.
AB  - The apple fruit moth Argyresthia conjugella (Lepidoptera, Yponomeutidae) is a
      seed predator of rowan (Sorbus aucuparia) and is distributed in Europe and Asia.
      In Fennoscandia (Finland, Norway and Sweden), rowan fruit production is low every
      2-4 years, and apple (Malus domestica) functions as an alternative host,
      resulting in economic loss in apple crops in inter-mast years. We have used
      Illumina MiSeq sequencing to identify a set of 19 novel tetra-nucleotide short
      tandem repeats (STRs) in Argyresthia conjugella. Such motifs are recommended for
      genetic monitoring, which may help to determine the eco-evolutionary processes
      acting on this pest insect. The 19 STRs were optimized and amplified into five
      multiplex PCR reactions. We tested individuals collected from Norway and Sweden
      (n = 64), and detected very high genetic variation (average 13.6 alleles, He =
      0.75) compared to most other Lepidoptera species studied so far. Spatial genetic
      differentiation was low and gene flow was high in the test populations, although
      two non-spatial clusters could be detected. We conclude that this set of genetic
      markers may be a useful resource for population genetic monitoring of this
      economical important insect species.

PMID- 29642499
TI  - Cimetidine: A Safe Treatment Option for Cutaneous Warts in Pediatric Heart
      Transplant Recipients.
AB  - Abstract:Background andObjectives: Immunosuppressed individuals are at
      particularly increased risk for human papilloma virus-related infections. The
      primary objective of our study is to determine if there are any adverse effects
      associated with high-dose cimetidine treatment. A secondary objective is to
      report our experience with cimetidine in the treatment of cutaneous warts in
      pediatric heart transplant recipients. Methods and Results: This was a
      retrospective observational study. A total of 8 pediatric heart transplant
      recipients diagnosed with multiple recalcitrant warts were the subject of the
      study. All patients were treated with cimetidine (30-40 mg/kg/day) in two divided
      doses for 3 to 6 month durations. All patients had complete resolution of their
      lesions except 1 patient who had no clinical improvement. Of these 8 patients,
      one had recurrence of warts at one year follow-up, which resolved with restarting
      cimetidine therapy. One patient who had only 3 months of cimetidine therapy had
      immediate relapse after cimetidine was stopped. None of them had significant
      change in their tacrolimus trough, serum creatinine, and alanine transaminase
      levels. No adverse events were reported except one patient experienced mild
      gynecomastia. Conclusion: Cimetidine can be a safe and alternative treatment
      option for multiple warts in pediatric heart transplant recipients.

PMID- 29642500
TI  - Antibacterial Free Fatty Acids and Monoglycerides: Biological Activities,
      Experimental Testing, and Therapeutic Applications.
AB  - Antimicrobial lipids such as fatty acids and monoglycerides are promising
      antibacterial agents that destabilize bacterial cell membranes, causing a wide
      range of direct and indirect inhibitory effects. The goal of this review is to
      introduce the latest experimental approaches for characterizing how antimicrobial
      lipids destabilize phospholipid membranes within the broader scope of introducing
      current knowledge about the biological activities of antimicrobial lipids,
      testing strategies, and applications for treating bacterial infections. To this
      end, a general background on antimicrobial lipids, including structural
      classification, is provided along with a detailed description of their targeting
      spectrum and currently understood antibacterial mechanisms. Building on this
      knowledge, different experimental approaches to characterize antimicrobial lipids
      are presented, including cell-based biological and model membrane-based
      biophysical measurement techniques. Particular emphasis is placed on drawing out
      how biological and biophysical approaches complement one another and can yield
      mechanistic insights into how the physicochemical properties of antimicrobial
      lipids influence molecular self-assembly and concentration-dependent interactions
      with model phospholipid and bacterial cell membranes. Examples of possible
      therapeutic applications are briefly introduced to highlight the potential
      significance of antimicrobial lipids for human health and medicine, and to
      motivate the importance of employing orthogonal measurement strategies to
      characterize the activity profile of antimicrobial lipids.

PMID- 29642501
TI  - Isolation of Bioactive Compounds from Calicotome villosa Stems.
AB  - A phenylethanoid, two steroids, a flavone glucoside and a chalcone have been
      isolated for the first time from the stems of Calicotome villosa together with a
      previously isolated flavone glucoside. Their structures were determined by
      spectroscopic analyses (NMR, HRMS) as basalethanoid B (1), beta-sitosterol and
      stigmasterol (2), chrysine-7-O-beta-d-glucopyranoside (3), chrysine 7-((6''-O
      acetyl)-O-beta-d-glucopyranoside) (4) and calythropsin (5). The crude extracts
      and the isolated compounds (except 4), were evaluated for their antioxidant,
      antimicrobial (against two Gram-positive bacterial strains: Staphylococcus
      aureus, Bacillus cereus, four Gram-negative bacterial strains: Staphylococcus
      epidermidis, Klebsiella pneumonia, Acinetobacter baumanii, and three yeasts:
      Candida albicans, Candida tropicalis, and Candida glabrata), hemolytic,
      antidiabetic, anti-inflammatory and cytotoxic activity. The crude extracts showed
      good ability to scavenge the free radical DPPH. Methanol stem extract followed by
      the dichloromethane stem extract showed moderate antimicrobial potency;
      furthermore, at 1 mg/mL the methanol extract showed an inhibition of C. albicans
      growth comparable to nystatin. Dichloromethane, methanol, and aqueous extracts
      inhibited 98%, 90%, and 80% of HeLa cell proliferation at 2 mg/mL respectively.
      Weak hypoglycemic and hemolytic effects were exhibited by the crude extracts.
      Among all the tested compounds, compound 3 showed remarkable hypoglycemic
      potential (93% at 0.1 mg/mL) followed by compound 5 (90% at 0.3 mg/mL). Compound
      5 was the most effective in the DPPH. scavenging assay (100% at 0.1 mg/mL) and
      cytotoxic assay on HeLa cells (99% and 90% after 24 and 48 h of treatment at 0.1
      mg/mL, respectively). No anti-inflammatory effects were displayed by any of the
      crude extracts or the isolated compounds at any of the tested concentrations.

PMID- 29642502
TI  - A 3D Microfluidic Model to Recapitulate Cancer Cell Migration and Invasion.
AB  - We have developed a microfluidic-based culture chip to simulate cancer cell
      migration and invasion across the basement membrane. In this microfluidic chip, a
      3D microenvironment is engineered to culture metastatic breast cancer cells (MX1)
      in a 3D tumor model. A chemo-attractant was incorporated to stimulate motility
      across the membrane. We validated the usefulness of the chip by tracking the
      motilities of the cancer cells in the system, showing them to be migrating or
      invading (akin to metastasis). It is shown that our system can monitor cell
      migration in real time, as compare to Boyden chambers, for example. Thus, the
      chip will be of interest to the drug-screening community as it can potentially be
      used to monitor the behavior of cancer cell motility, and, therefore, metastasis,
      in the presence of anti-cancer drugs.

PMID- 29642504
TI  - Alteration of Hepatic Gene Expression along with the Inherited Phenotype of
      Acquired Fatty Liver in Chicken.
AB  - Fatty liver is a widespread disease in chickens that causes a decrease in egg
      production and even death. The characteristics of the inherited phenotype of
      acquired fatty liver and the molecular mechanisms underlying it, however, are
      largely unknown. In the current study, fatty liver was induced in 3 breeds by a
      high-fat (HF) diet and a methionine choline-deficient (MCD) diet. The results
      showed that the dwarf Jingxing-Huang (JXH) chicken was more susceptible to fatty
      liver compared with the layer White Leghorns (WL) and local Beijing-You (BJY)
      breeds. In addition, it was found that the paternal fatty livers induced by HF
      diet in JXH chickens were inherited. Compared to birds without fatty liver in the
      control group, both offsprings and their sires with fatty livers in the paternal
      group exhibited altered hepatic gene expression profiles, including upregulation
      of several key genes involved in fatty acid metabolism, lipid metabolism and
      glucose metabolism (ACACA, FASN, SCD, ACSL5, FADS2, FABP1, APOA4 and ME1). This
      study uniquely revealed that acquired fatty liver in cocks can be inherited. The
      hepatic gene expression profiles were altered in chickens with the inherited
      phenotype of acquired paternal fatty liver and several genes could be candidate
      biomarkers.

PMID- 29642505
TI  - BMP9 Promotes the Proliferation and Migration of Bladder Cancer Cells through Up
      Regulating lncRNA UCA1.
AB  - As the most common malignant tumor of the urinary system worldwide, the bladder
      tumor has a high mortality rate, which is mainly due to its onset of concealment.
      Therefore, research into novel diagnostic markers and treatment of bladder cancer
      is urgently needed. BMP9 (Bone morphogenetic protein 9) is a member of BMP, which
      belongs to the TGF-beta (transforming growth factor-beta) superfamily. It has
      been associated with multiple tumors. We found that BMP9 is highly expressed in
      bladder cancer cells and it could significantly promote the proliferation and
      migration of bladder cancer cells. In the study of the mechanism of this effect,
      we found that BMP9 can increase the expression of lncRNA UCA1 (Urothelial cancer
      associated 1) through phosphorylated AKT. The promoting effect of BMP9 on bladder
      cancer cells was rescued after interfering with UCA1 in BMP9 overexpressed
      bladder cancer cells both in vitro and in vivo. Our research confirms that BMP9
      promotes the proliferation and migration of bladder cancer cells through up
      regulated lncRNA UCA1. It also shows that BMP9 is a novel diagnostic marker and a
      potential therapeutic target in bladder cancer.

PMID- 29642506
TI  - FPGA Based Adaptive Rate and Manifold Pattern Projection for Structured Light 3D
      Camera System.
AB  - The quality of the captured point cloud and the scanning speed of a structured
      light 3D camera system depend upon their capability of handling the object
      surface of a large reflectance variation in the trade-off of the required number
      of patterns to be projected. In this paper, we propose and implement a flexible
      embedded framework that is capable of triggering the camera single or multiple
      times for capturing single or multiple projections within a single camera
      exposure setting. This allows the 3D camera system to synchronize the camera and
      projector even for miss-matched frame rates such that the system is capable of
      projecting different types of patterns for different scan speed applications.
      This makes the system capturing a high quality of 3D point cloud even for the
      surface of a large reflectance variation while achieving a high scan speed. The
      proposed framework is implemented on the Field Programmable Gate Array (FPGA),
      where the camera trigger is adaptively generated in such a way that the position
      and the number of triggers are automatically determined according to camera
      exposure settings. In other words, the projection frequency is adaptive to
      different scanning applications without altering the architecture. In addition,
      the proposed framework is unique as it does not require any external memory for
      storage because pattern pixels are generated in real-time, which minimizes the
      complexity and size of the application-specific integrated circuit (ASIC) design
      and implementation.

PMID- 29642507
TI  - A Fiber Bragg Grating Interrogation System with Self-Adaption Threshold Peak
      Detection Algorithm.
AB  - A Fiber Bragg Grating (FBG) interrogation system with a self-adaption threshold
      peak detection algorithm is proposed and experimentally demonstrated in this
      study. This system is composed of a field programmable gate array (FPGA) and
      advanced RISC machine (ARM) platform, tunable Fabry-Perot (F-P) filter and
      optical switch. To improve system resolution, the F-P filter was employed. As
      this filter is non-linear, this causes the shifting of central wavelengths with
      the deviation compensated by the parts of the circuit. Time-division multiplexing
      (TDM) of FBG sensors is achieved by an optical switch, with the system able to
      realize the combination of 256 FBG sensors. The wavelength scanning speed of 800
      Hz can be achieved by a FPGA+ARM platform. In addition, a peak detection
      algorithm based on a self-adaption threshold is designed and the peak recognition
      rate is 100%. Experiments with different temperatures were conducted to
      demonstrate the effectiveness of the system. Four FBG sensors were examined in
      the thermal chamber without stress. When the temperature changed from 0  degrees
      C to 100  degrees C, the degree of linearity between central wavelengths and
      temperature was about 0.999 with the temperature sensitivity being 10 pm/ degrees
      C. The static interrogation precision was able to reach 0.5 pm. Through the
      comparison of different peak detection algorithms and interrogation approaches,
      the system was verified to have an optimum comprehensive performance in terms of
      precision, capacity and speed.

PMID- 29642508
TI  - ECCM Scheme against Interrupted Sampling Repeater Jammer Based on Parameter
      Adjusted Waveform Design.
AB  - Interrupted sampling repeater jamming (ISRJ) is an effective way of deceiving
      coherent radar sensors, especially for linear frequency modulated (LFM) radar. In
      this paper, for a simplified scenario with a single jammer, we propose a dynamic
      electronic counter-counter measure (ECCM) scheme based on jammer parameter
      estimation and transmitted signal design. Firstly, the LFM waveform is
      transmitted to estimate the main jamming parameters by investigating the
      discontinuousness of the ISRJ's time-frequency (TF) characteristics. Then, a
      parameter-adjusted intra-pulse frequency coded signal, whose ISRJ signal after
      matched filtering only forms a single false target, is designed adaptively
      according to the estimated parameters, i.e., sampling interval, sampling duration
      and repeater times. Ultimately, for typical jamming scenes with different jamming
      signal ratio (JSR) and duty cycle, we propose two particular ISRJ suppression
      approaches. Simulation results validate the effective performance of the proposed
      scheme for countering the ISRJ, and the trade-off relationship between the two
      approaches is demonstrated.

PMID- 29642503
TI  - Migration/Invasion of Malignant Gliomas and Implications for Therapeutic
      Treatment.
AB  - Malignant tumors of the central nervous system (CNS) are among cancers with the
      poorest prognosis, indicated by their association with tumors of high-level
      morbidity and mortality. Gliomas, the most common primary CNS tumors that arise
      from neuroglial stem or progenitor cells, have estimated annual incidence of 6.6
      per 100,000 individuals in the USA, and 3.5 per 100,000 individuals in Taiwan.
      Tumor invasion and metastasis are the major contributors to the deaths in cancer
      patients. Therapeutic goals including cancer stem cells (CSC), phenotypic shifts,
      EZH2/AXL/TGF-beta axis activation, miRNAs and exosomes are relevant to GBM
      metastasis to develop novel targeted therapeutics for GBM and other brain
      cancers. Herein, we highlight tumor metastasis in our understanding of gliomas,
      and illustrate novel exosome therapeutic approaches in glioma, thereby paving the
      way towards innovative therapies in neuro-oncology.

PMID- 29642509
TI  - In-Situ Synthesis of Hydrogen Titanate Nanotube/Graphene Composites with a
      Chemically Bonded Interface and Enhanced Visible Photocatalytic Activity.
AB  - Hydrogen titanate nanotube (HTT)/graphene nanocomposites are synthesized by
      hydrothermal reduction of graphene oxide (GO) and simultaneous preparation of
      nanotubular HTT via an alkaline hydrothermal process. By using this facile in
      situ compositing strategy, HTT are densely supported upon the surface of graphene
      sheets with close interface contacts. The as-prepared HTT/graphene nanocomposites
      possess significantly enhanced visible light catalytic activity for the partial
      oxidation of benzylic alcohols. The amount of graphene has significant influence
      on catalytic activity and the optimal content of graphene is 1.0 wt %, giving a
      normalized rate constant k of 1.71 * 10-3 g/m2.h, which exceeds that of pure HTT
      and HTT/graphene-1.0% mixed by a factor of 7.1 or 5.2. Other than the general
      role of graphene as a high-performance electron acceptor or transporter, the
      observed enhancement in photocatalytic activity over HTT/graphene can be ascribed
      to the improved interfacial charge migration from enhanced chemical bonding (Ti-C
      bonds) during the in-situ compositing process. The formation of Ti-C bonds is
      confirmed by XPS analysis and the resulting enhanced separation of photoinduced
      charge carriers is demonstrated by electrochemical impedance spectra and
      transient photocurrent response.

PMID- 29642511
TI  - Effect of Pinocembrin Isolated from Mexican Brown Propolis on Diabetic
      Nephropathy.
AB  - Propolis is a resinous beehive product that has been used worldwide in
      traditional medicine to prevent and treat colds, wounds, rheumatism, heart
      disease and diabetes. Diabetic nephropathy is the final stage of renal
      complications caused by diabetes and for its treatment there are few
      alternatives. The present study aimed to determine the chemical composition of
      three propolis samples collected in Chihuahua, Durango and Zacatecas and to
      evaluate the effect of pinocembrin in a model of diabetic nephropathy in vivo.
      Previous research demonstrated that propolis of Chihuahua possesses hypoglycemic
      and antioxidant activities. Two different schemes were assessed, preventive
      (before renal damage) and corrective (once renal damage is established). In the
      preventive scheme, pinocembrin treatment avoids death of the rats, improves lipid
      profile, glomerular filtration rate, urinary protein, avoid increases in urinary
      biomarkers, oxidative stress and glomerular basement membrane thickness. Whereas,
      in the corrective scheme, pinocembrin only improves lipid profile without showing
      improvement in any other parameters, even pinocembrin exacerbated the damage. In
      conclusion, pinocembrin ameliorates diabetic nephropathy when there is no kidney
      damage but when it is already present, pinocembrin accelerates kidney damage.

PMID- 29642510
TI  - Dietary Patterns Associated with Cognitive Function among the Older People in
      Underdeveloped Regions: Finding from the NCDFaC Study.
AB  - Although dietary patterns are crucial to cognitive function, associations of
      dietary patterns with cognitive function have not yet been fully understood. This
      cross-sectional study explored dietary patterns associated with cognitive
      function among the older adults in underdeveloped regions, using 1504 community
      dwelling older adults aged 60 and over. Diet was assessed using a food frequency
      questionnaire and 24-h dietary recall. Factor analysis was used to extract
      dietary patterns. Global cognitive function was assessed using the Mini-Mental
      State Examination (MMSE). Two dietary patterns, a "mushroom, vegetable, and
      fruits" (MVF) pattern and a "meat and soybean products" (MS) pattern, were
      identified. The MVF pattern, characterized by high consumption of mushrooms,
      vegetables, and fruits was significantly positively associated with cognitive
      function (p < 0.05), with an odds ratio of (95% CIs) 0.60 (0.38, 0.94) for
      cognitive impairment and beta (95% CIs) 0.15 (0.02, 0.29) for -log (31-MMSE
      score). The MS pattern, characterized by high consumption of soybean products and
      meat, was also associated with better cognitive function, with an odds ratio of
      0.47 (95% CIs 0.30, 0.74) for cognitive impairment and beta (95% CIs) 0.34 (0.21,
      0.47) for -log (31-MMSE score). Our results suggested that both the MVF and MS
      patterns were positively associated with better cognitive function among older
      adults in underdeveloped regions.

PMID- 29642512
TI  - Finite Element Simulations of Hard-On-Soft Hip Joint Prosthesis Accounting for
      Dynamic Loads Calculated from a Musculoskeletal Model during Walking.
AB  - The hip joint replacement is one of the most successful orthopedic surgical
      procedures although it involves challenges to overcome. The patient group
      undergoing total hip arthroplasty now includes younger and more active patients
      who require a broad range of motion and a longer service lifetime for the
      replacement joint. It is well known that wear tests have a long duration and they
      are very expensive, thus studying the effects of geometry, loading, or alignment
      perturbations may be performed by Finite Element Analysis. The aim of the study
      was to evaluate total deformation and stress intensity on ultra-high molecular
      weight polyethylene liner coupled with hard material head during one step. Moving
      toward in-silico wear assessment of implants, in the presented simulations we
      used a musculoskeletal multibody model of a human body giving the loading and
      relative kinematic of the investigated tribo-system during the gait. The analysis
      compared two frictional conditions -dry and wet and two geometrical cases- with
      and without radial clearance. The loads and rotations followed the variability of
      the gait cycle as well as stress/strain acting in the UHWMPE cup. The obtained
      results allowed collection of the complete stress/strain description of the
      polyethylene cup during the gait and calculation of the maximum contact pressure
      on the lateral edge of the insert. The tensional state resulted in being more
      influenced by the geometrical conditions in terms of radial clearance than by the
      variation of the friction coefficients due to lubrication phenomena.

PMID- 29642513
TI  - Intra-Household Allocation of Nutrients in an Opening China.
AB  - This paper uses China Health and Nutrition Survey (CHNS) data to analyze the
      effect of foreign direct investment (FDI) on nutrient intakes across various
      family roles to identify the different family roles' heterogeneous nutrition
      intake responses to economic openness. The empirical evidence shows that FDI
      enhances labor forces' calorie intake significantly, especially for rural
      households. The government should continue facilitating more FDI inflows,
      especially FDI in secondary industries for rural populations. However, the larger
      the family, the smaller the effect of FDI on nutrient intake for some family
      roles. The elderly and children may be weaker responders on nutrient intake than
      other family members in an open economy. This implies the existence of intra
      household redistribution and that the level of effectiveness will decrease with
      family size. The results suggest that family members in rural areas can benefit
      more in terms of nutrient intake. Our empirical evidence also indicates that
      female family members' calorie intake from the FDI effect is higher than that of
      male family members (except for the granddaughter/grandson). Preferential
      policies should be provided for the FDI, flowing to rural areas and female
      dominant industries.

PMID- 29642514
TI  - An Intelligent Monitoring Network for Detection of Cracks in Anvils of High-Press
      Apparatus.
AB  - Due to the endurance of alternating high pressure and temperature, the carbide
      anvils of the high-press apparatus, which are widely used in the synthetic
      diamond industry, are prone to crack. In this paper, an acoustic method is used
      to monitor the crack events, and the intelligent monitoring network is proposed
      to classify the sound samples. The pulse sound signals produced by such cracking
      are first extracted based on a short-time energy threshold. Then, the signals are
      processed with the proposed intelligent monitoring network to identify the
      operation condition of the anvil of the high-pressure apparatus. The monitoring
      network is an improved convolutional neural network that solves the problems that
      may occur in practice. The length of pulse sound excited by the crack growth is
      variable, so a spatial pyramid pooling layer is adopted to solve the variable
      length input problem. An adaptive weighted algorithm for loss function is
      proposed in this method to handle the class imbalance problem. The good
      performance regarding the accuracy and balance of the proposed intelligent
      monitoring network is validated through the experiments finally.

PMID- 29642515
TI  - Biocatalyst Screening with a Twist: Application of Oxygen Sensors Integrated in
      Microchannels for Screening Whole Cell Biocatalyst Variants.
AB  - Selective oxidative functionalization of molecules is a highly relevant and often
      demanding reaction in organic chemistry. The use of biocatalysts allows the
      stereo- and regioselective introduction of oxygen molecules in organic compounds
      at milder conditions and avoids the use of complex group-protection schemes and
      toxic compounds usually applied in conventional organic chemistry. The
      identification of enzymes with the adequate properties for the target reaction
      and/or substrate requires better and faster screening strategies. In this
      manuscript, a microchannel with integrated oxygen sensors was applied to the
      screening of wild-type and site-directed mutated variants of naphthalene
      dioxygenase (NDO) from Pseudomonas sp. NICB 9816-4. The oxygen sensors were used
      to measure the oxygen consumption rate of several variants during the conversion
      of styrene to 1-phenylethanediol. The oxygen consumption rate allowed the
      distinguishing of endogenous respiration of the cell host from the oxygen
      consumed in the reaction. Furthermore, it was possible to identify the higher
      activity and different reaction rate of two variants, relative to the wild-type
      NDO. The meander microchannel with integrated oxygen sensors can therefore be
      used as a simple and fast screening platform for the selection of dioxygenase
      mutants, in terms of their ability to convert styrene, and potentially in terms
      of substrate specificity.

PMID- 29642516
TI  - Erratum: Ramanathan, A.; et al. Metal-Incorporated Mesoporous Silicates: Tunable
      Catalytic Properties and Applications. Molecules 2018, 23, 263.
AB  - The authors wish to make the following change to their paper [1].[...].

PMID- 29642517
TI  - Asymptomatic Effect of Occupational Radiation Exposure on Thyroid Gland Hormones
      and Thyroid Gland Ultrasonographic Abnormalities.
AB  - Data evaluating the effect of asymptomatic effects of radiation on thyroid
      hormone panels and ultrasonographic abnormalities among radiology technologists
      are scarce. This study aimed to determine the asymptomatic effect of radiation in
      a total of 39 male and 11 female exposed radiology technologists working in
      radiology departments, and a total of 34 male and 16 female age-matched controls
      working in other departments in the same hospital. The level of triiodothyronine
      (T3), thyroxine (T4) and thyroid-stimulating hormone (TSH) were evaluated using
      Enzyme Linked Immunosorbent Assay (ELISA). Thyroid ultrasonographic evaluation
      outcomes were given as normal or abnormal. There was significant interaction
      between exposure and gender in the mean TSH and T4 but not T3. The mean TSH for
      exposed men was significantly higher than that among non-exposed men (2.28 mIU/L
      vs. 1.59 mIU/L; p-value = 0.003). The mean TSH was not significantly different
      between exposed and non-exposed women. The mean T4 for exposed men was
      significantly higher when compared with non-exposed men (11.1 pmol/L vs. 10.05
      pmol/L; p-value = 0.005). In the non-exposed group, 93.8% of women and 94.1% of
      men had T4 values lower than established normal reference range, while in the
      exposed group, 90.9% of women and 74.4% of men had low values of T4. There was no
      significant difference in mean T3 between exposed and non-exposed groups for men
      and women. Furthermore, there were no significant differences in the thyroid
      gland ultrasonographic findings between exposed and non-exposed groups.
      Occupational radiation exposure is associated with increased means of TSH and T3,
      especially among men.

PMID- 29642518
TI  - Absolute Measurement of the Refractive Index of Water by a Mode-Locked Laser at
      518 nm.
AB  - In this paper, we demonstrate a method using a frequency comb, which can
      precisely measure the refractive index of water. We have developed a simple
      system, in which a Michelson interferometer is placed into a quartz-glass
      container with a low expansion coefficient, and for which compensation of the
      thermal expansion of the water container is not required. By scanning a mirror on
      a moving stage, a pair of cross-correlation patterns can be generated. We can
      obtain the length information via these cross-correlation patterns, with or
      without water in the container. The refractive index of water can be measured by
      the resulting lengths. Long-term experimental results show that our method can
      measure the refractive index of water with a high degree of accuracy-measurement
      uncertainty at 10-5 level has been achieved, compared with the values calculated
      by the empirical formula.

PMID- 29642519
TI  - Beneficial Effects of Bioactive Compounds in Mulberry Fruits against Cisplatin
      Induced Nephrotoxicity.
AB  - Mulberry, the fruit of white mulberry tree (Morus alba L., Moraceae), is commonly
      used in traditional Chinese medicines as a sedative, tonic, laxative, and emetic.
      In our continuing research of the bioactive metabolites from mulberry, chemical
      analysis of the fruits led to the isolation of five compounds, 1-5. The compounds
      were identified as butyl pyroglutamate (1), quercetin 3-O-beta-d-glucoside (2),
      kaempferol 3-O-beta-d-rutinoside (3), rutin (4), and 2-phenylethyl d-rutinoside
      (5) by spectroscopic data analysis, comparing their nuclear magnetic resonance
      (NMR) data with those in published literature, and liquid chromatography-mass
      spectrometry analysis. The isolated compounds 1-5 were evaluated for their
      effects on anticancer drug-induced side effects by cell-based assays. Compound 1
      exerted the highest protective effect against cisplatin-induced kidney cell
      damage. This effect was found to be mediated through the attenuation of
      phosphorylation of c-Jun N-terminal kinase, extracellular signal-regulated
      kinase, p38, mitogen-activated protein kinase, and caspase-3 in cisplatin-induced
      kidney cell damage.

PMID- 29642520
TI  - Melatonin Protects against Lung Fibrosis by Regulating the Hippo/YAP Pathway.
AB  - Idiopathic pulmonary fibrosis (IPF) is a progressive, fibrotic interstitial
      pneumonia with high mortality. Melatonin, a hormone predominantly secreted by the
      pineal gland, has been reported to participate in the process of IPF. However,
      the mechanisms underlying the effect of melatonin in pulmonary fibrosis have not
      been elucidated to date. This study was designed to evaluate the anti-fibrotic
      role of melatonin in pulmonary fibrosis and to elucidate the potential
      mechanisms. We observed that melatonin markedly attenuated bleomycin (BLM)
      induced experimental lung fibrosis in mice and inhibited TGF-beta1-induced
      fibrogenesis in lung fibroblasts. Additionally, we determined that luzindole, a
      melatonin receptor inhibitor, reduced the anti-fibrotic effect of melatonin.
      Further studies showed that melatonin alleviated the translocation of YAP1 from
      cytoplasm to nucleus, a key downstream effector of the Hippo pathway, in vivo and
      in vitro by interacting with its receptor. Taken together, our results suggest
      that melatonin prevents lung fibrosis by inhibiting YAP1 and indicate that
      melatonin replacement could be a novel strategy for the treatment of lung
      fibrosis.

PMID- 29642521
TI  - Cytochrome P450 CYP6EV11 in Chironomus kiiensis Larvae Involved in Phenol Stress.
AB  - Phenol is one of the organic pollutants which can cause water environment
      pollution. It is not only enriched in aquatic organisms but is also a serious
      threat to human health. Chironomus kiiensis is very sensitive to the contaminants
      in water and its cytochrome P450s are usually chosen as biomarkers for water
      pollution. To examine whether CYP6EV11 plays a role in the oxidative metabolism
      of phenol, we measured the silencing efficiency of CYP6EV11 and evaluated larval
      susceptibility to sublethal phenol levels by RNA interference (RNAi) technology.
      The results showed that the transcription of CYP6EV11 was found significantly up
      regulated when the 4th instar C.kiiensis larvae were exposed to three doses of
      phenol. However, the transcriptional levels of CYP6EV11 were significantly
      suppressed by 92.7% in the 4th instar C. kiiensis larvae soaked in dsCYP6EV11
      compared with those soaked in dsGFP for 6 h. The CYP6EV11 expression and
      mortality of the 4th instar C. kiiensis larvae with CYP6EV11 silencing were
      mostly decreased under phenol stress. Therefore, the CYP6EV11 gene may be used as
      a molecular biomarker for earlier warning and monitoring for water pollution.

PMID- 29642522
TI  - Cellulose-Silica Nanocomposites of High Reinforcing Content with Fungi Decay
      Resistance by One-Pot Synthesis.
AB  - Hybrid bionanocomposites based on cellulose matrix, with silica nanoparticles as
      reinforcers, were prepared by one-pot synthesis of cellulose surface modified by
      solvent exchange method to keep the biopolymer net void for hosting inorganic
      nanoparticles. Neither expensive inorganic-particle precursors nor crosslinker
      agents or catalysts were used for effective dispersion of reinforcer
      concentration up to 50 wt %. Scanning electron microscopy of the nanocomposites
      shows homogeneous dispersion of reinforcers in the surface modified cellulose
      matrix. The FTIR spectra demonstrated the cellulose features even at 50 weight
      percent content of silica nanoparticles. Such a high content of silica provides
      high thermal stability to composites, as seen by TGA-DSC. The fungi decay
      resistance to Trametes versicolor was measured by standard test showing good
      resistance even with no addition of antifungal agents. This one-pot synthesis of
      biobased hybrid materials represents an excellent way for industrial production
      of high performance materials, with a high content of inorganic nanoparticles,
      for a wide variety of applications.

PMID- 29642523
TI  - Tricycloalternarene Analogs from a Symbiotic Fungus Aspergillus sp. D and Their
      Antimicrobial and Cytotoxic Effects.
AB  - Bioassay-guided fractionation of the crude extract of fermentation broth of one
      symbiotic strain Aspergillus sp. D from the coastal plant Edgeworthia chrysantha
      Lindl. led to isolation of one new meroterpenoid, tricycloalternarene 14b (1),
      together with four known analogs (2-5), tricycloalternarenes 2b (2), 3a (3), 3b
      (4), and ACTG-toxin F (5). Their chemical structures were unambiguously
      established on the basis of NMR, mass spectrometry, and optical rotation data
      analysis, as well as by comparison with literature data. Biological assays
      indicated that compound 2 exhibited potent in vitro cytotoxicity against human
      lung adenocarcinoma A549 cell line with an IC50 value of 2.91 MUM, and compound 5
      had a moderate inhibitory effect on Candida albicans, with an MIC value of 15.63
      MUM. The results indicated that this symbiotic strain D is an important producer
      of tricycloalternarene derivatives, with potential therapeutic application in
      treatment of cancer and pathogen infection.

PMID- 29642524
TI  - Medical and Legal Aspects of Child Sexual Abuse: A Population-Based Study in a
      Hungarian County.
AB  - BACKGROUND: Very few studies focus on childhood sexual abuse in middle European
      countries. AIM: The purpose of our study is to describe the medical and legal
      characteristics of children who experience sexual abuse and explore common
      features that may result in strategies for prevention. METHODS: Between 2000 and
      2015, 400 girls and 26 boys under the age of 18, suspected of being sexually
      abused, visited one of the four hospitals in a Hungarian county. RESULTS: Mean
      age at onset was 10.81 years for boys, 13.46 years for girls. In 278 cases
      (65.3%), the perpetrator was known to the victim, and a stranger was suspected in
      148 cases (34.7%). In 79 cases (30.7% of boys and 17.7% of girls), a family
      member was the accused perpetrator. In more than one-third (boys) and in one
      fifth (girls) of cases, sexual abuse had occurred on multiple occasions. In the
      case of boys, child and adolescent sexual abuse (CSA) included oral genital,
      genital touching and genital to genital contact in 14 cases (53.8%) and anal
      intercourse in 12 (46.2%) cases. In case of girls, sexual abuse included coitus
      in 219 (54.8%), oral genital, genital touching, genital to genital contact in 164
      (41.0%), anal abuse in 14 (3.5%) cases, physical injury was incurred in 15 cases.
      Legal proceedings followed the CSA in 205 (48.1%) cases. CONCLUSION: The results
      highlight the urgent need to address the issue of sexual abuse in Hungary and
      minimize its impact. Prevention requires a systematic and lifelong approach to
      educating children about personal space safety and privacy to reduce
      vulnerability and is the responsibility of parents and professionals.

PMID- 29642525
TI  - Multi-Objectives Optimization of Ventilation Controllers for Passive Cooling in
      Residential Buildings.
AB  - An inappropriate indoor climate, mostly indoor temperature, may cause occupants'
      discomfort. There are a great number of air conditioning systems that make it
      possible to maintain the required thermal comfort. Their installation, however,
      involves high investment costs and high energy demand. The study analyses the
      possibilities of limiting too high a temperature in residential buildings using
      passive cooling by means of ventilation with ambient cool air. A fuzzy logic
      controller whose aim is to control mechanical ventilation has been proposed and
      optimized. In order to optimize the controller, the modified Multiobjective
      Evolutionary Algorithm, based on the Strength Pareto Evolutionary Algorithm, has
      been adopted. The optimization algorithm has been implemented in MATLAB(r), which
      is coupled by MLE+ with EnergyPlus for performing dynamic co-simulation between
      the programs. The example of a single detached building shows that the occupants'
      thermal comfort in a transitional climate may improve significantly owing to
      mechanical ventilation controlled by the suggested fuzzy logic controller. When
      the system is connected to the traditional cooling system, it may further bring
      about a decrease in cooling demand.

PMID- 29642526
TI  - Construction and Characterization of a Humanized Anti-Epstein-Barr Virus gp350
      Antibody with Neutralizing Activity in Cell Culture.
AB  - Acute Epstein-Barr virus (EBV) infection in immunosuppressed transplant patients
      can give rise to a malignant B-cell proliferation known as post-transplant
      lymphoproliferative disease (PTLD). The EBV major virion surface glycoprotein
      (gp)350 is a principal target of naturally occurring neutralizing antibodies and
      is viewed as the best target to prevent acute infection and PTLD in at-risk
      transplant recipients. We have constructed a humanized (hu) version of the murine
      anti-gp350 neutralizing monoclonal antibody 72a1. The hu72a1 IgG1 antibody
      displayed no significant anti-mouse activity, recognized both gp350 and its
      splice variant gp220 as well as a gp350 peptide that was shown to constitute the
      principal EBV gp350 neutralizing epitope when tested in immunoassays. Hu72a1
      antibody blocked in vitro EBV infection of B cells at a level which equaled that
      of a mouse-human chimeric 72a1 antibody construct. This work provides a further
      structural and immunological understanding of the 72a1 antibody interaction with
      EBV gp350, and constitutes a launch point for future anti-EBV therapeutic
      antibodies designed to block EBV infection and prevent PTLD while eliminating the
      deleterious antigenic murine features of the original 72a1 antibody.

PMID- 29642527
TI  - Fluid Intake and Beverage Consumption Description and Their Association with
      Dietary Vitamins and Antioxidant Compounds in Italian Adults from the
      Mediterranean Healthy Eating, Aging and Lifestyles (MEAL) Study.
AB  - The aim of the present study was to investigate the total water intake (TWI) from
      drinks and foods and to evaluate the correlation between the different types of
      drinks on energy and antioxidant intake. The cohort comprised 1602 individuals
      from the city of Catania in Southern Italy. A food frequency questionnaire was
      administered to assess dietary and water intake. The mean total water intake was
      2.7 L; more than about two thirds of the sample met the European recommendations
      for water intake. Water and espresso coffee were the most consumed drinks.
      Alcohol beverages contributed about 3.0% of total energy intake, and sugar
      sweetened beverages contributed about 1.4%. All antioxidant vitamins were
      significantly correlated with TWI. However, a higher correlation was found for
      water from food rather than water from beverages, suggesting that major food
      contributors to antioxidant vitamin intake might be fruits and vegetables, rather
      than beverages other than water. A mild correlation was found between fruit
      juices and vitamin C; coffee, tea and alcohol, and niacin and polyphenols; and
      milk and vitamin B12. The findings from the present study show that our sample
      population has an adequate intake of TWI and that there is a healthy association
      between beverages and dietary antioxidants.

PMID- 29642528
TI  - The Effect of Topical Ocular Anesthetic Proparacaine on Conjunctival and Nasal
      Mucosal Flora in Dry Eye Disease Patients.
AB  - The aim of this study was to investigate the effect of topically applied ocular
      anesthetic proparacaine on conjunctival and nasal bacterial mucosal flora in
      patients with dry eye disease. A Schirmer test was done with (group 1) and
      without (group 2) topical anesthetic proparacaine to 40 patients in each group.
      Conjunctival and nasal cultures were obtained before and 10 min after performing
      the Schirmer test. The bacterial culture results and the isolated bacteria were
      recorded in two groups. Patients' mean age was 62 years (70 female, 10 male).
      Before the application of topical anesthetic, 50 (62.5%) and 62 (77.5%) had
      positive conjunctival and nasal culture, respectively, with the most commonly
      isolated organism being coagulase-negative Staphylococcus in each group. In group
      1 the conjunctival bacterial culture positivity rate decreased from 26 (65%) to
      six (15%) eyes (p < 0.001); however, this rate decreased slightly from 24 (60%)
      to 20 (50%) eyes in group 2 (p > 0.05). For the nasal cultures, the bacterial
      culture positivity rate decreased from 80% to 20% and from 75% to 65% in groups 1
      (p < 0.001) and 2 (p > 0.05), respectively. Topical ocular anesthetic
      proparacaine has antibacterial activity in both conjunctival and nasal flora in
      patients with dry eye disease.

PMID- 29642529
TI  - A Novel Pb-Resistant Bacillus subtilis Bacterium Isolate for Co-Biosorption of
      Hazardous Sb(III) and Pb(II): Thermodynamics and Application Strategy.
AB  - The present work is the first to study co-biosorption of Pb(II) and Sb(III) by a
      novel bacterium and its application strategy. The biosorption characteristics of
      Pb(II) and Sb(III) ions from aqueous solution using B. subtilis were
      investigated. Optimum pH, biomass dosage, contact time and temperature were
      determined to be 5.00, 6.00 mg/L, 45 min and 35  degrees C, respectively.
      Langmuir, Freundlich, Temkin and Dubinin-Radushkevich (D-R) models were applied
      to describe the biosorption isotherm of the metal ions by B. subtilis. Results
      showed that Langmuir model fitted the equilibrium data of Pb(II) better than
      others, while biosorption of Sb(III) obeyed the Freundlich model well. The
      biosorption capacity of B. subtilis biomass for Pb(II) and Sb(III) ions was found
      to be 17.34 +/- 0.14 and 2.32 +/- 0.30 mg/g, respectively. Kinetic data showed
      the biosorption process of Pb(II) and Sb(III) ions both followed the pseudo
      second-order kinetic model, with R2 ranging from 0.974 to 0.999 for Pb(II) and
      from 0.967 to 0.979 for Sb(III). The calculated thermodynamic parameters,
      negative ?G and positive ?H and ?S values, indicated the biosorption of Pb(II)
      and Sb(III) ions onto B. subtilis biomass in water was feasible, endothermic, and
      spontaneous. Bacterial bioleaching experiment revealed B. subtilis can increase
      the mobility of Pb(II) and Sb(III) in polluted soil when pH was close to 6 at low
      temperature. Consequently, B. subtilis, as a cheap and original bacterial
      material, could be a promising biomass to remove Pb or isolate Sb from industrial
      wastewater and to assist phytoremediation of Pb and Sb from weak acid or near
      neutral pH polluted soils at low temperature.

PMID- 29642530
TI  - An Innovative Context-Based Crystal-Growth Activity Space Method for
      Environmental Exposure Assessment: A Study Using GIS and GPS Trajectory Data
      Collected in Chicago.
AB  - Scholars in the fields of health geography, urban planning, and transportation
      studies have long attempted to understand the relationships among human movement,
      environmental context, and accessibility. One fundamental question for this
      research area is how to measure individual activity space, which is an indicator
      of where and how people have contact with their social and physical environments.
      Conventionally, standard deviational ellipses, road network buffers, minimum
      convex polygons, and kernel density surfaces have been used to represent people's
      activity space, but they all have shortcomings. Inconsistent findings of the
      effects of environmental exposures on health behaviors/outcomes suggest that the
      reliability of existing studies may be affected by the uncertain geographic
      context problem (UGCoP). This paper proposes the context-based crystal-growth
      activity space as an innovative method for generating individual activity space
      based on both GPS trajectories and the environmental context. This method not
      only considers people's actual daily activity patterns based on GPS tracks but
      also takes into account the environmental context which either constrains or
      encourages people's daily activity. Using GPS trajectory data collected in
      Chicago, the results indicate that the proposed new method generates more
      reasonable activity space when compared to other existing methods. This can help
      mitigate the UGCoP in environmental health studies.

PMID- 29642531
TI  - A Possible Trifunctional beta-Carotene Synthase Gene Identified in the Draft
      Genome of Aurantiochytrium sp. Strain KH105.
AB  - Labyrinthulomycetes have been regarded as a promising industrial source of
      xanthophylls, including astaxanthin and canthaxanthin, polyunsaturated fatty
      acids such as docosahexaenoic acid and docosapentaenoic acid, omega-3 oils, and
      terpenic hydrocarbons, such as sterols and squalene. A Thraustochytrid,
      Aurantiochytrium sp. KH105 produces carotenoids, including astaxanthin, with
      strong antioxidant activity. To gain genomic insights into this capacity, we
      decoded its 97-Mbp genome and characterized genes for enzymes involved in
      carotenoid biosynthesis. Interestingly, all carotenogenic genes, as well as other
      eukaryotic genes, appeared duplicated, suggesting that this strain is diploid. In
      addition, among the five genes involved in the pathway from geranylgeranyl
      pyrophosphate to astaxanthin, geranylgeranyl phytoene synthase (crtB), phytoene
      desaturase (crtI) and lycopene cyclase (crtY) were fused into single gene
      (crtIBY) with no internal stop codons. Functionality of the trifunctional enzyme,
      CrtIBY, to catalyze the reaction from geranylgeranyl diphosphate to beta-carotene
      was confirmed using a yeast assay system and mass spectrometry. Furthermore,
      analyses of differential gene expression showed characteristic up-regulation of
      carotenoid biosynthetic genes during stationary and starvation phases under these
      culture conditions. This suggests genetic engineering events to promote more
      efficient production of carotenoids. We also showed an occurrence of crtIBY in
      other Thraustochytrid species.

PMID- 29642532
TI  - Ursodeoxycholate Restores Biliary Excretion of Methotrexate in Rats with Ethinyl
      Estradiol Induced-Cholestasis by Restoring Canalicular Mrp2 Expression.
AB  - The in vivo relevance of ursodeoxycholate (UDCA) treatment (100 mg/kg/day, per
      oral tid for 5 days before cholestasis induction followed by the same dosing for
      5 days) on hepatic function was investigated in rats with 17alpha
      ethinylestradiol (EE, 10 mg/kg, subcutaneous for 5 days)-induced experimental
      cholestasis. The bile flow rate and the expression level of hepatic multidrug
      resistance-associated protein 2 (Mrp 2) that were decreased in cholestasis were
      restored after UDCA treatment. Consistent with this, the biliary excretion
      clearance (CLexc,bile) of a representative Mrp2 substrate-methotrexate (MTX)-was
      decreased in cholestatic rats but was restored after UDCA treatment.
      Consequently, the plasma concentrations of MTX, which were increased by
      cholestasis, were decreased to control levels by UDCA treatment. Thus, the
      restoration of CLexc,bile appears to be associated with the increase in Mrp2
      expression on the canalicular membrane by UDCA treatment followed by Mrp2
      mediated biliary excretion of MTX. On the other hand, the hepatic uptake
      clearance (CLup,liver) of MTX was unchanged by cholestasis or UDCA treatment,
      suggestive of the absence of any association between the uptake process and the
      overall biliary excretion of MTX. Since UDCA has been known to induce the
      expression of canalicular MRP2 in humans, UDCA treatment might be effective in
      humans to maintain or accelerate the hepatobiliary elimination of xenobiotics or
      metabolic conjugates that are MRP2 substrates.

PMID- 29642533
TI  - Rhabdomyolysis in a Young Girl with Van Wyk-Grumbach Syndrome due to Severe
      Hashimoto Thyroiditis.
AB  - Background: Autoimmune hypothyroidism (Hashimoto thyroiditis; HT) is the most
      common postnatal thyroid disease. Clinical manifestations of HT vary according to
      disease severity. Due to the pleiotropic effects of thyroid hormone, less common
      signs and symptoms of HT can occur, leading to a delay in diagnosis. Case
      presentation: A 9-year-old girl of Indian origin was admitted for a one-week
      history of widespread myalgia, fatigue, muscle weakness, difficulty walking, and
      a significant increase in weight (approximately 2 kg) without any changes in
      daily habits. The only relevant medical history was several intermittent vaginal
      bleeding episodes since four years of age. Breast development was consistent with
      Tanner stage 2 without pubic or axillary hair; while height and weight were at
      the 10th percentile and the 38th percentile; respectively. Bone age from a left
      wrist X-ray was delayed 1 year. Pelvic ultrasonography revealed a uterine
      body/neck ratio of >1 (pubertal stage) and multifollicular ovaries. Her external
      genitalia had a childlike appearance. Laboratory examinations showed an increased
      thyroid-stimulating hormone, decreased free thyroxine, and positive anti
      thyroglobulin antibody titres, as well as elevation of creatine phosphokinase,
      myoglobin, lactate dehydrogenase, serum aspartate aminotransferase,
      hypercholesterolemia, and a basal serum prolactin near the upper limit of normal.
      Follicle stimulating hormone and estradiol were slightly and significantly
      elevated, respectively. Thyroid ultrasound showed an increased gland size with
      irregular echostructures and high vascularization. Levothyroxine replacement
      therapy led to complete normalization of clinical and laboratory findings,
      including rhabdomyolysis indices. No further vaginal bleeding episodes were
      reported. Conclusion: This case report highlights how various can be the clinical
      picture of HT in children, and how rare clinical manifestations can be the only
      signs of disease at presentation leading to delayed diagnosis and treatment. In
      this girl, a never-described association of Van Wyk-Grumbach syndrome and acute
      rhabdomyolysis in a young girl with previously unrecognized HT is described. The
      importance of recognizing the signs and symptoms of rare complications of HT in
      order to begin appropriate therapy is stressed.

PMID- 29642535
TI  - Molecular Targeting of Acid Ceramidase in Glioblastoma: A Review of Its Role,
      Potential Treatment, and Challenges.
AB  - Glioblastoma is the most common, malignant primary tumor of the central nervous
      system. The average prognosis for life expectancy after diagnosis, with the triad
      of surgery, chemotherapy, and radiation therapy, is less than 1.5 years.
      Chemotherapy treatment is mostly limited to temozolomide. In this paper, the
      authors review an emerging, novel drug called acid ceramidase, which targets
      glioblastoma. Its role in cancer treatment in general, and more specifically, in
      the treatment of glioblastoma, are discussed. In addition, the authors provide
      insights on acid ceramidase as a potential druggable target for glioblastoma.

PMID- 29642536
TI  - Multi-Component Analysis of Ilex Kudingcha C. J. Tseng by a Single Marker
      Quantification Method and Chemometric Discrimination of HPLC Fingerprints.
AB  - The quantitative analysis of multiple components with a single marker (QAMS)
      method was firstly established for simultaneous determination of 18 active
      components in Ilex kudingcha C. J. Tseng by HPLC. Using rutin, isochlorogenic
      acid A and kudinoside A as internal refererence substances (IRS), compatibility
      results showed that the relative correction factors (RCFs) of all compounds
      showed good reproducibility under different chromatographic conditions. On the
      basis of previous studies, the accuracy of the QAMS method was systematically
      evaluated by investigating the influences of curve intercept, analytes and IRS
      concentration. The results showed that the concentration (especially at low
      level) of analytes and curve intercept were the major influencing parameters for
      the LRG-QAMS method (LRG = linear regression), whereas the influence of IRS
      concentration seemed more apparent in terms of the AVG-QAMS method (AVG =
      average). The two approaches were complementary with each other. In addition,
      hierarchical clustering analysis (HCA), principal components analysis (PCA) and
      similarity analysis (SA) were performed to differentiate and classify the samples
      based on the contents of 18 marker compounds. The results of the different
      chemometric analyses were completely consistent with each other, and could be
      supported by the quantification results.

PMID- 29642534
TI  - Mesenchymal Stromal Cells: Emerging Roles in Bone Metastasis.
AB  - Bone metastasis is the most advanced stage of many cancers and indicates a poor
      prognosis for patients due to resistance to anti-tumor therapies. The
      establishment of metastasis within the bone is a multistep process. To ensure
      survival within the bone marrow, tumor cells must initially colonize a niche in
      which they can enter dormancy. Subsequently, reactivation permits the
      proliferation and growth of the tumor cells, giving rise to a macro-metastasis
      displayed clinically as a bone metastatic lesion. Here, we review the evidences
      that suggest mesenchymal stromal cells play an important role in each of these
      steps throughout the development of bone metastasis. Similarities between the
      molecular mechanisms implicated in these processes and those involved in the
      homeostasis of the bone indicate that the metastatic cells may exploit the
      homeostatic processes to their own advantage. Identifying the molecular
      interactions between the mesenchymal stromal cells and tumor cells that promote
      tumor development may offer insight into potential therapeutic targets that could
      be utilized to treat bone metastasis.

PMID- 29642539
TI  - In Silico Functional Networks Identified in Fish Nucleated Red Blood Cells by
      Means of Transcriptomic and Proteomic Profiling.
AB  - Nucleated red blood cells (RBCs) of fish have, in the last decade, been
      implicated in several immune-related functions, such as antiviral response,
      phagocytosis or cytokine-mediated signaling. RNA-sequencing (RNA-seq) and label
      free shotgun proteomic analyses were carried out for in silico functional pathway
      profiling of rainbow trout RBCs. For RNA-seq, a de novo assembly was conducted,
      in order to create a transcriptome database for RBCs. For proteome profiling, we
      developed a proteomic method that combined: (a) fractionation into cytosolic and
      membrane fractions, (b) hemoglobin removal of the cytosolic fraction, (c) protein
      digestion, and (d) a novel step with pH reversed-phase peptide fractionation and
      final Liquid Chromatography Electrospray Ionization Tandem Mass Spectrometric (LC
      ESI-MS/MS) analysis of each fraction. Combined transcriptome- and proteome-
      sequencing data identified, in silico, novel and striking immune functional
      networks for rainbow trout nucleated RBCs, which are mainly linked to innate and
      adaptive immunity. Functional pathways related to regulation of hematopoietic
      cell differentiation, antigen presentation via major histocompatibility complex
      class II (MHCII), leukocyte differentiation and regulation of leukocyte
      activation were identified. These preliminary findings further implicate
      nucleated RBCs in immune function, such as antigen presentation and leukocyte
      activation.

PMID- 29642538
TI  - DDX5 RNA Helicases: Emerging Roles in Viral Infection.
AB  - Asp-Glu-Ala-Asp (DEAD)-box polypeptide 5 (DDX5), also called p68, is a
      prototypical member of the large ATP-dependent RNA helicases family and is known
      to participate in all aspects of RNA metabolism ranging from transcription to
      translation, RNA decay, and miRNA processing. The roles of DDX5 in cell cycle
      regulation, tumorigenesis, apoptosis, cancer development, adipogenesis, Wnt-beta
      catenin signaling, and viral infection have been established. Several RNA viruses
      have been reported to hijack DDX5 to facilitate various steps of their
      replication cycles. Furthermore, DDX5 can be bounded by the viral proteins of
      some viruses with unknown functions. Interestingly, an antiviral function of DDX5
      has been reported during hepatitis B virus and myxoma virus infection. Thus, the
      precise roles of this apparently multifaceted protein remain largely obscure.
      Here, we provide a rapid and critical overview of the structure and functions of
      DDX5 with a particular emphasis on its role during virus infection.

PMID- 29642537
TI  - Epigenetic Mechanisms Impacting Aging: A Focus on Histone Levels and Telomeres.
AB  - Aging and age-related diseases pose some of the most significant and difficult
      challenges to modern society as well as to the scientific and medical
      communities. Biological aging is a complex, and, under normal circumstances,
      seemingly irreversible collection of processes that involves numerous underlying
      mechanisms. Among these, chromatin-based processes have emerged as major
      regulators of cellular and organismal aging. These include DNA methylation,
      histone modifications, nucleosome positioning, and telomere regulation, including
      how these are influenced by environmental factors such as diet. Here we focus on
      two interconnected categories of chromatin-based mechanisms impacting aging:
      those involving changes in the levels of histones or in the functions of
      telomeres.

PMID- 29642540
TI  - Instillation of Sericin Enhances Corneal Wound Healing through the ERK Pathway in
      Rat Debrided Corneal Epithelium.
AB  - Sericin is a major constituent of silk produced by silkworms. We previously found
      that the instillation of sericin enhanced the proliferation of corneal epithelial
      cells, and acted to promote corneal wound healing in both normal and diabetic
      model rats. However, the mechanisms by which sericin promotes the proliferation
      of corneal cells have not been established. In this study, we investigated the
      effects of sericin on Akt and ERK activation in a human corneal epithelial cell
      line (HCE-T cells) and rat debrided corneal epithelium. Although Akt
      phosphorylation was not detected following the treatment of HCE-T cells with
      sericin, ERK1/2 phosphorylation was enhanced. The growth of HCE-T cells treated
      with sericin was significantly increased, with the cell growth of sericin-treated
      HCE-T cells being 1.7-fold higher in comparison with vehicle-treated HCE-T cells.
      On the other hand, both of an ERK inhibitor U0126 (non-specific specific
      inhibitor) and SCH772984 (specific inhibitor) attenuated the enhanced cell growth
      by sericin, and the growth level in the case of co-treatment with sericin and
      ERK1/2 inhibitor was similar to that of cells treated with ERK1/2 inhibitor
      alone. In an in vivo study using rat debrided corneal epithelium, the corneal
      wound healing rate was enhanced by the instillation of sericin, and this
      enhancement was also attenuated by the instillation of U0126. In addition, the
      corneal wound healing rate in rats co-instilled with sericin and U0126 was
      similar to that following the instillation of U0126 alone. In conclusion, we
      found that the instillation of sericin enhanced cell proliferation via the
      activation of the MAPK/ERK pathway, resulting in the promotion of corneal wound
      healing in rat eyes. These findings provide significant information for designing
      further studies to develop potent corneal wound-healing drugs.

PMID- 29642541
TI  - Influence of Dietary Supplementation of Propolis and Bee Pollen on Liver
      Pathology in Broiler Chickens.
AB  - One of the major problems in intensive breeding of chickens is liver damage. The
      objective of this study was to determine the influence of dietary supplementation
      with propolis and bee pollen on liver pathology in broiler chickens. The study
      was conducted on 200 Ross 308 chickens equally distributed by sex that were
      divided into five groups. Throughout the whole study, the control group of
      chickens was fed with a basal diet, while the experimental groups of chickens
      were fed with the same diet further supplemented with propolis and bee pollen,
      each supplement given separately or in combination in a certain proportion. The
      study showed that the clusters of lymphocytes in the hepatocytes, the vacuolar
      degeneration and necrosis of the liver parenchyma, the bile ductule hyperplasia,
      and the various forms of pathological changes in the liver arteries and veins
      were more frequent in liver tissue samples of the control group compared to liver
      tissue samples of all the experimental groups (p < 0.001). The study further
      showed that all the previously mentioned histopathological lesions of liver
      tissue were always more extensive in the liver tissue samples of the control
      group than in the liver tissue samples of all the experimental groups (p <
      0.001). The supplementation of broiler chickens with propolis and/or bee pollen
      has a strong protective effect on liver pathology in broiler chickens.

PMID- 29642543
TI  - Comparative Genomics and Transcriptome Profiling in Primary Aldosteronism.
AB  - Primary aldosteronism is the most common form of endocrine hypertension with a
      prevalence of 6% in the general population with hypertension. The genetic basis
      of the four familial forms of primary aldosteronism (familial hyperaldosteronism
      FH types I-IV) and the majority of sporadic unilateral aldosterone-producing
      adenomas has now been resolved. Familial forms of hyperaldosteronism are,
      however, rare. The sporadic forms of the disease prevail and these are usually
      caused by either a unilateral aldosterone-producing adenoma or bilateral adrenal
      hyperplasia. Aldosterone-producing adenomas frequently carry a causative somatic
      mutation in either of a number of genes with the KCNJ5 gene, encoding an inwardly
      rectifying potassium channel, a recurrent target harboring mutations at a
      prevalence of more than 40% worldwide. Other than genetic variations, gene
      expression profiling of aldosterone-producing adenomas has shed light on the
      genes and intracellular signalling pathways that may play a role in the
      pathogenesis and pathophysiology of these tumors.

PMID- 29642544
TI  - Quality Assessment of Kumu Injection, a Traditional Chinese Medicine Preparation,
      Using HPLC Combined with Chemometric Methods and Qualitative and Quantitative
      Analysis of Multiple Alkaloids by Single Marker.
AB  - Kumu injection (KMI) is a common-used traditional Chinese medicine (TCM)
      preparation made from Picrasma quassioides (D. Don) Benn. rich in alkaloids. An
      innovative technique for quality assessment of KMI was developed using high
      performance liquid chromatography (HPLC) combined with chemometric methods and
      qualitative and quantitative analysis of multi-components by single marker
      (QAMS). Nigakinone (PQ-6, 5-hydroxy-4-methoxycanthin-6-one), one of the most
      abundant alkaloids responsible for the major pharmacological activities of Kumu,
      was used as a reference substance. Six alkaloids in KMI were quantified,
      including 6-hydroxy-beta-carboline-1-carboxylic acid (PQ-1), 4,5-dimethoxycanthin
      6-one (PQ-2), beta-carboline-1-carboxylic acid (PQ-3), beta-carboline-1-propanoic
      acid (PQ-4), 3-methylcanthin-5,6-dione (PQ-5), and PQ-6. Based on the outcomes of
      twenty batches of KMI samples, the contents of six alkaloids were used for
      further chemometric analysis. By hierarchical cluster analysis (HCA), radar
      plots, and principal component analysis (PCA), all the KMI samples could be
      categorized into three groups, which were closely related to production date and
      indicated the crucial influence of herbal raw material on end products of KMI.
      QAMS combined with chemometric analysis could accurately measure and clearly
      distinguish the different quality samples of KMI. Hence, QAMS is a feasible and
      promising method for the quality control of KMI.

PMID- 29642542
TI  - Antibody-Drug Conjugates for Cancer Therapy: Chemistry to Clinical Implications.
AB  - Chemotherapy is one of the major therapeutic options for cancer treatment.
      Chemotherapy is often associated with a low therapeutic window due to its poor
      specificity towards tumor cells/tissues. Antibody-drug conjugate (ADC) technology
      may provide a potentially new therapeutic solution for cancer treatment. ADC
      technology uses an antibody-mediated delivery of cytotoxic drugs to the tumors in
      a targeted manner, while sparing normal cells. Such a targeted approach can
      improve the tumor-to-normal tissue selectivity and specificity in chemotherapy.
      Considering its importance in cancer treatment, we aim to review recent efforts
      for the design and development of ADCs. ADCs are mainly composed of an antibody,
      a cytotoxic payload, and a linker, which can offer selectivity against tumors,
      anti-cancer activity, and stability in systemic circulation. Therefore, we have
      reviewed recent updates and principal considerations behind ADC designs, which
      are not only based on the identification of target antigen, cytotoxic drug, and
      linker, but also on the drug-linker chemistry and conjugation site at the
      antibody. Our review focuses on site-specific conjugation methods for producing
      homogenous ADCs with constant drug-antibody ratio (DAR) in order to tackle
      several drawbacks that exists in conventional conjugation methods.

PMID- 29642545
TI  - Chloroplast Genome of the Folk Medicine and Vegetable Plant Talinum paniculatum
      (Jacq.) Gaertn.: Gene Organization, Comparative and Phylogenetic Analysis.
AB  - The complete chloroplast (cp) genome of Talinum paniculatum (Caryophyllale), a
      source of pharmaceutical efficacy similar to ginseng, and a widely distributed
      and planted edible vegetable, were sequenced and analyzed. The cp genome size of
      T. paniculatum is 156,929 bp, with a pair of inverted repeats (IRs) of 25,751 bp
      separated by a large single copy (LSC) region of 86,898 bp and a small single
      copy (SSC) region of 18,529 bp. The genome contains 83 protein-coding genes, 37
      transfer RNA (tRNA) genes, eight ribosomal RNA (rRNA) genes and four pseudogenes.
      Fifty one (51) repeat units and ninety two (92) simple sequence repeats (SSRs)
      were found in the genome. The pseudogene rpl23 (Ribosomal protein L23) was insert
      AATT than other Caryophyllale species by sequence alignment, which located in IRs
      region. The gene of trnK-UUU (tRNA-Lys) and rpl16 (Ribosomal protein L16) have
      larger introns in T. paniculatum, and the existence of matK (maturase K) genes,
      which usually located in the introns of trnK-UUU, rich sequence divergence in
      Caryophyllale. Complete cp genome comparison with other eight Caryophyllales
      species indicated that the differences between T. paniculatum and P. oleracea
      were very slight, and the most highly divergent regions occurred in intergenic
      spacers. Comparisons of IR boundaries among nine Caryophyllales species showed
      that T. paniculatum have larger IRs region and the contraction is relatively
      slight. The phylogenetic analysis among 35 Caryophyllales species and two
      outgroup species revealed that T. paniculatum and P. oleracea do not belong to
      the same family. All these results give good opportunities for future
      identification, barcoding of Talinum species, understanding the evolutionary mode
      of Caryophyllale cp genome and molecular breeding of T. paniculatum with high
      pharmaceutical efficacy.

PMID- 29642546
TI  - The Brown Midrib Leaf (bml) Mutation in Rice (Oryza sativa L.) Causes Premature
      Leaf Senescence and the Induction of Defense Responses.
AB  - Isolating and characterizing mutants with altered senescence phenotypes is one of
      the ways to understand the molecular basis of leaf aging. Using ethyl methane
      sulfonate mutagenesis, a new rice (Oryza sativa) mutant, brown midrib leaf (bml),
      was isolated from the indica cultivar 'Zhenong34'. The bml mutants had brown
      midribs in their leaves and initiated senescence prematurely, at the onset of
      heading. The mutants had abnormal cells with degraded chloroplasts and contained
      less chlorophyll compared to the wild type (WT). The bml mutant showed excessive
      accumulation of reactive oxygen species (ROS), increased activities of superoxide
      dismutase, catalase, and malondialdehyde, upregulation of senescence-induced STAY
      GREEN genes and senescence-related transcription factors, and down regulation of
      photosynthesis-related genes. The levels of abscisic acid (ABA) and jasmonic acid
      (JA) were increased in bml with the upregulation of some ABA and JA biosynthetic
      genes. In pathogen response, bml demonstrated higher resistance against
      Xanthomonas oryzae pv. oryzae and upregulation of four pathogenesis-related genes
      compared to the WT. A genetic study confirmed that the bml trait was caused by a
      single recessive nuclear gene (BML). A map-based cloning using insertion/deletion
      markers confirmed that BML was located in the 57.32kb interval between the L5IS7
      and L5IS11 markers on the short arm of chromosome 5. A sequence analysis of the
      candidate region identified a 1 bp substitution (G to A) in the 5'-UTR (+98) of
      bml. BML is a candidate gene associated with leaf senescence, ROS regulation, and
      disease response, also involved in hormone signaling in rice. Therefore, this
      gene might be useful in marker-assisted backcrossing/gene editing to improve rice
      cultivars.

PMID- 29642548
TI  - The Strange Case of Peri-Implantology.

PMID- 29642547
TI  - Antiplatelet Therapy in Coronary Artery Disease: A Daunting Dilemma.
AB  - Percutaneous coronary intervention (PCI) with stenting for the treatment of acute
      coronary syndrome (ACS) is the contemporary standard of care. Such treatment is
      followed by dual antiplatelet therapy (DAPT) comprising of aspirin and a P2Y12
      inhibitor. The efficacy of this therapy has been well established but the optimal
      duration of DAPT remains elusive, and has thus far attracted a prodigious deal of
      scientific attention. The decision regarding DAPT duration can be clinically
      challenging in the modern era with the evolution of newer stents, more potent
      antiplatelet agents, and novel anticoagulant drugs in addition to an older
      patient population with multiple comorbidities. Major societal guidelines have
      emphasized comprehensive assessment of ischemic and bleeding risk, in turn
      recommending individualization of DAPT duration, thus encouraging "shared
      decision making". The following review is aimed at critically evaluating the
      available evidence to help make these crucial clinical decisions regarding
      duration of DAPT and triple therapy.

PMID- 29642549
TI  - A SINS/SRS/GNS Autonomous Integrated Navigation System Based on Spectral Redshift
      Velocity Measurements.
AB  - In order to meet the requirements of autonomy and reliability for the navigation
      system, combined with the method of measuring speed by using the spectral
      redshift information of the natural celestial bodies, a new scheme, consisting of
      Strapdown Inertial Navigation System (SINS)/Spectral Redshift (SRS)/Geomagnetic
      Navigation System (GNS), is designed for autonomous integrated navigation
      systems. The principle of this SINS/SRS/GNS autonomous integrated navigation
      system is explored, and the corresponding mathematical model is established.
      Furthermore, a robust adaptive central difference particle filtering algorithm is
      proposed for this autonomous integrated navigation system. The simulation
      experiments are conducted and the results show that the designed SINS/SRS/GNS
      autonomous integrated navigation system possesses good autonomy, strong
      robustness and high reliability, thus providing a new solution for autonomous
      navigation technology.

PMID- 29642550
TI  - Healing of Osteochondral Defects Implanted with Biomimetic Scaffolds of
      Poly(epsilon-Caprolactone)/Hydroxyapatite and Glycidyl-Methacrylate-Modified
      Hyaluronic Acid in a Minipig.
AB  - Articular cartilage is a structure lack of vascular distribution. Once the
      cartilage is injured or diseased, it is unable to regenerate by itself. Surgical
      treatments do not effectively heal defects in articular cartilage. Tissue
      engineering is the most potential solution to this problem. In this study,
      methoxy poly(ethylene glycol)-block-poly(epsilon-caprolactone) (mPEG-PCL) and
      hydroxyapatite at a weight ratio of 2:1 were mixed via fused deposition modeling
      (FDM) layer by layer to form a solid scaffold. The scaffolds were further
      infiltrated with glycidyl methacrylate hyaluronic acid loading with 10 ng/mL of
      Transforming Growth Factor-beta1 and photo cross-linked on top of the scaffolds.
      An in vivo test was performed on the knees of Lanyu miniature pigs for a period
      of 12 months. The healing process of the osteochondral defects was followed by
      computer tomography (CT). The defect was fully covered with regenerated tissues
      in the control pig, while different tissues were grown in the defect of knee of
      the experimental pig. In the gross anatomy of the cross section, the scaffold
      remained in the subchondral location, while surface cartilage was regenerated.
      The cross section of the knees of both the control and experimental pigs were
      subjected to hematoxylin and eosin staining. The cartilage of the knee in the
      experimental pig was partially matured, e.g., few chondrocyte cells were enclosed
      in the lacunae. In the knee of the control pig, the defect was fully grown with
      fibrocartilage. In another in vivo experiment in a rabbit and a pig, the
      composite of the TGF-beta1-loaded hydrogel and scaffolds was found to regenerate
      hyaline cartilage. However, scaffolds that remain in the subchondral lesion
      potentially delay the healing process. Therefore, the structural design of the
      scaffold should be reconsidered to match the regeneration process of both
      cartilage and subchondral bone.

PMID- 29642551
TI  - N-Aryl-7-hydroxy-5-oxo-2,3-dihydro-1H,5H-pyrido-[3,2,1-ij]quinoline-6
      carboxamides. The Synthesis and Effects on Urinary Output.
AB  - Continuing a targeted search for new leading structures with diuretic action
      among tricyclic derivatives of hydroxyquinolines, which are of interest as
      potential inhibitors of aldosterone synthase, the synthesis of a series of the
      corresponding pyrido[3,2,1-ij]quinoline-6-carboxanilides was carried out by
      amidation of ethyl-7-hydroxy-5-oxo-2,3-dihydro-1H,5H-pyrido[3,2,1-ij]quinoline-6
      carboxylate with aniline, aminophenols and O-alkylsubstituted analogs with high
      yields and purity. The optimal conditions of this reaction are proposed; they
      make it possible to prevent partial destruction of the original heterocyclic
      ester and thereby avoid formation of specific impurities of 7-hydroxy-2,3-dihydro
      1H,5H-pyrido[3,2,1-ij]quinolin-5-one. To confirm the structure of all substances
      obtained, elemental analysis, nuclear magnetic resonance (NMR) spectroscopy, and
      mass spectrometry were used. Moreover, the peculiarities of their 1H and 13C-NMR
      spectra, as well as their mass spectrometric behavior under conditions of
      electron impact ionization, were discussed. The effect of pyrido[3,2,1
      ij]quinoline-6-carboxanilides on the urinary function of the kidneys was studied
      in white rats of both genders by the standard method of oral administration at a
      dose of 10 mg/kg. Testing was conducted in comparison with hydrochlorothiazide,
      as well as with structurally close pyrrolo[3,2,1-ij] quinoline-5-carboxanilides
      studied earlier with the same substituents in the anilide fragments. It was found
      that addition of one methylene unit to the heterocycle partially hydrogenated and
      annelated with the quinolone core has a positive impact on biological properties
      most of the substances studied exhibit a statistically significant diuretic
      effect exceeding the activity of not only hydrochlorothiazide, in some cases, but
      also the action of the structural analogs. The important structural and
      biological regularities, which are common with pyrroloquinolines and introduced
      by a chemical modification, were revealed. The importance of the presence in the
      structure of terminal amide fragments of tricyclic quinoline-3-carboxamides of a
      4-methoxy-substituted aromatic ring was particularly marked. The expediency of
      further study of pyridoquinolines as promising diuretic agents has been shown.

PMID- 29642552
TI  - Three-Dimensional Registration for Handheld Profiling Systems Based on Multiple
      Shot Structured Light.
AB  - In this article, a multi-view registration approach for the 3D handheld profiling
      system based on the multiple shot structured light technique is proposed. The
      multi-view registration approach is categorized into coarse registration and
      point cloud refinement using the iterative closest point (ICP) algorithm. Coarse
      registration of multiple point clouds was performed using relative orientation
      and translation parameters estimated via homography-based visual navigation. The
      proposed system was evaluated using an artificial human skull and a paper box
      object. For the quantitative evaluation of the accuracy of a single 3D scan, a
      paper box was reconstructed, and the mean errors in its height and breadth were
      found to be 9.4 MUm and 23 MUm, respectively. A comprehensive quantitative
      evaluation and comparison of proposed algorithm was performed with other variants
      of ICP. The root mean square error for the ICP algorithm to register a pair of
      point clouds of the skull object was also found to be less than 1 mm.

PMID- 29642554
TI  - Maritime over the Horizon Sensor Integration: High Frequency Surface-Wave-Radar
      and Automatic Identification System Data Integration Algorithm.
AB  - To obtain the complete operational picture of the maritime situation in the
      Exclusive Economic Zone (EEZ) which lies over the horizon (OTH) requires the
      integration of data obtained from various sensors. These sensors include: high
      frequency surface-wave-radar (HFSWR), satellite automatic identification system
      (SAIS) and land automatic identification system (LAIS). The algorithm proposed in
      this paper utilizes radar tracks obtained from the network of HFSWRs, which are
      already processed by a multi-target tracking algorithm and associates SAIS and
      LAIS data to the corresponding radar tracks, thus forming an integrated data
      pair. During the integration process, all HFSWR targets in the vicinity of AIS
      data are evaluated and the one which has the highest matching factor is used for
      data association. On the other hand, if there is multiple AIS data in the
      vicinity of a single HFSWR track, the algorithm still makes only one data pair
      which consists of AIS and HFSWR data with the highest mutual matching factor.
      During the design and testing, special attention is given to the latency of AIS
      data, which could be very high in the EEZs of developing countries. The algorithm
      is designed, implemented and tested in a real working environment. The testing
      environment is located in the Gulf of Guinea and includes a network of HFSWRs
      consisting of two HFSWRs, several coastal sites with LAIS receivers and SAIS data
      provided by provider of SAIS data.

PMID- 29642555
TI  - A Novel Design Framework for Structures/Materials with Enhanced Mechanical
      Performance.
AB  - Abstract: Structure/material requires simultaneous consideration of both its
      design and manufacturing processes to dramatically enhance its manufacturability,
      assembly and maintainability. In this work, a novel design framework for
      structural/material with a desired mechanical performance and compelling
      topological design properties achieved using origami techniques is presented. The
      framework comprises four procedures, including topological design, unfold,
      reduction manufacturing, and fold. The topological design method, i.e., the solid
      isotropic material penalization (SIMP) method, serves to optimize the structure
      in order to achieve the preferred mechanical characteristics, and the origami
      technique is exploited to allow the structure to be rapidly and easily
      fabricated. Topological design and unfold procedures can be conveniently
      completed in a computer; then, reduction manufacturing, i.e., cutting, is
      performed to remove materials from the unfolded flat plate; the final structure
      is obtained by folding out the plate from the previous procedure. A series of
      cantilevers, consisting of origami parallel creases and Miura-ori (usually
      regarded as a metamaterial) and made of paperboard, are designed with the least
      weight and the required stiffness by using the proposed framework. The findings
      here furnish an alternative design framework for engineering structures that
      could be better than the 3D-printing technique, especially for large structures
      made of thin metal materials.

PMID- 29642553
TI  - Genomic Profiling on an Unselected Solid Tumor Population Reveals a Highly
      Mutated Wnt/beta-Catenin Pathway Associated with Oncogenic EGFR Mutations.
AB  - Oncogenic epidermal growth factor receptors (EGFRs) can recruit key effectors in
      diverse cellular processes to propagate oncogenic signals. Targeted and
      combinational therapeutic strategies have been successfully applied for treating
      EGFR-driven cancers. However, a main challenge in EGFR therapies is drug
      resistance due to mutations, oncogenic shift, alternative signaling, and other
      potential mechanisms. To further understand the genetic alterations associated
      with oncogenic EGFRs and to provide further insight into optimal and personalized
      therapeutic strategies, we applied a proprietary comprehensive next-generation
      sequencing (NGS)-based assay of 435 genes to systematically study the genomic
      profiles of 1565 unselected solid cancer patient samples. We found that
      activating EGFR mutations were predominantly detected in lung cancer,
      particularly in non-small cell lung cancer (NSCLC). The mutational landscape of
      EGFR-driven tumors covered most key signaling pathways and biological processes.
      Strikingly, the Wnt/beta-catenin pathway was highly mutated (48 variants detected
      in 46% of the EGFR-driven tumors), and its variant number topped that in the
      TP53/apoptosis and PI3K-AKT-mTOR pathways. Furthermore, an analysis of mutation
      distribution revealed a differential association pattern of gene mutations
      between EGFR exon 19del and EGFR L858R. Our results confirm the aggressive nature
      of the oncogenic EGFR-driven tumors and reassure that a combinational strategy
      should have advantages over an EGFR-targeted monotherapy and holds great promise
      for overcoming drug resistance.

PMID- 29642556
TI  - Reliability and Validity of the European Child Environment Questionnaire (ECEQ)
      in Children and Adolescents with Cerebral Palsy: Persian Version.
AB  - The aim of this study was to assess the reliability and validity of the Persian
      version of the European Child Environment Questionnaire (ECEQ) in the Iranian
      context. In total, 332 parents (20.2% fathers and 79.8% mothers) of children and
      adolescents with cerebral palsy (CP) with an average age of 12.33 years (min 7.08
      to max 18.08) from three provinces in Iran participated in the study. The
      original version of the questionnaire was translated and back-translated.
      Confirmatory construct validity was assessed by factor analysis and reliability
      was evaluated by Cronbach's alpha (N = 332) and after two weeks' test-retest
      reliability (n = 51) using an intraclass correlation coefficient (ICC). Eleven
      questions were dropped as they did not fit well into domains in the Persian
      version (p > 0.05). Cronbach's alpha and intraclass correlation coefficient in
      all domains and overall were acceptable (higher than 0.70) and significant (p >
      0.05). The Persian version of the ECEQ is suitable for assessing the needs and
      availability of environmental factors and is reliable and valid for children with
      CP, as reported by their parents.

PMID- 29642558
TI  - Confinement Effects on Chemical Equilibria: Pentacyano(Pyrazine)Ferrate(II)
      Stability Changes within Nanosized Droplets of Water.
AB  - Nanoscale confinement is known to impact properties of molecules and we observed
      changes in the reactivity of an iron coordination complex,
      pentacyano(pyrazine)ferrate(II). The confinement of two coordination complexes in
      a sodium AOT/isooctane reverse micellar (RM) water droplet was found to
      dramatically increase the hydrolysis rate of [Fe(CN)5pyz]3- and change the
      monomer-dimer equilibria between [Fe(CN)5pyz]3- and [Fe2(CN)10pyz]6-. Combined UV
      Vis and 1H-NMR spectra of these complexes in RMs were analyzed and the position
      of the monomer-dimer equilibrium and the relative reaction times were determined
      at three different RM sizes. The data show that the hydrolysis rates (loss of
      pyrazine) are dramatically enhanced in RMs over bulk water and increase as the
      size of the RM decreases. Likewise, the monomer-dimer equilibrium changes to
      favor the formation of dimer as the RM size decreases. We conclude that the
      effects of the [Fe(CN)5pyz]3- stability is related to its solvation within the
      RM.

PMID- 29642560
TI  - Near-Field Chipless Radio-Frequency Identification (RFID) Sensing and
      Identification System with Switching Reading.
AB  - A chipless radio-frequency identification (chipless-RFID) and sensing system,
      where tags are read by proximity (near-field) through a switch, is presented. The
      tags consist of a set of identical resonant elements (split-ring resonators or
      SRRs), printed or etched at predefined and equidistant positions, forming a
      linear chain, each SRR providing a bit of information. The logic state ('1' or
      '0') associated with each resonator depends on whether it is present or not in
      the predefined position. The reader is an array of power splitters used to feed a
      set of SRR-loaded transmission lines (in equal number to the number of resonant
      elements, or bits, of the tag). The feeding (interrogation) signal is a harmonic
      (single-tone) signal tuned to a frequency in the vicinity of the fundamental
      resonance of the SRRs. The set of SRR-loaded lines must be designed so that the
      corresponding SRRs are in perfect alignment with the SRRs of the tag, provided
      the tag is positioned on top of the reader. Thus, in a reading operation, as long
      as the tag is very close to the reader, the SRRs of the tag modify (decrease) the
      transmission coefficient of the corresponding reader line (through
      electromagnetic coupling between both SRRs), and the amplitude of the output
      signal is severely reduced. Therefore, the identification (ID) code of the tag is
      contained in the amplitudes of the output signals of the SRR-loaded lines, which
      can be inferred sequentially by means of a switching system. Unlike previous
      chipless-RFID systems based on near-field and sequential bit reading, the tags in
      the proposed system can be merely positioned on top of the reader, conveniently
      aligned, without the need to mechanically place them across the reader. Since tag
      reading is only possible if the tag is very close to the reader, this system can
      be also used as a proximity sensor with applications such as target
      identification. The proposed chipless-RFID and sensing approach is validated by
      reading a designed 4-bit tag. For identification purposes, this system is of
      special interest in applications where a low number of bits suffice, and tag
      reading by proximity is acceptable (or even convenient). Applications mostly
      related to secure paper, particularly involving a limited number of items (e.g.,
      exams, ballots, etc.), in order to provide authenticity and avoid counterfeiting,
      are envisaged. As a proximity sensor, the system may be of use in detecting and
      distinguishing different targets in applications such as smart packaging.

PMID- 29642557
TI  - A Mediterranean Diet Model in Australia: Strategies for Translating the
      Traditional Mediterranean Diet into a Multicultural Setting.
AB  - Substantial evidence supports the effect of the Mediterranean Diet (MD) for
      managing chronic diseases, although trials have been primarily conducted in
      Mediterranean populations. The efficacy and feasibility of the Mediterranean
      dietary pattern for the management of chronic diseases has not been extensively
      evaluated in non-Mediterranean settings. This paper aims to describe the
      development of a MD model that complies with principles of the traditional MD
      applied in a multiethnic context. Optimal macronutrient and food-based
      composition was defined, and a two-week menu was devised incorporating
      traditional ingredients with evidence based on improvements in chronic disease
      management. Strategies were developed for the implementation of the diet model in
      a multiethnic population. Consistent with the principles of a traditional MD, the
      MD model was plant-based and high in dietary fat, predominantly monounsaturated
      fatty acids from extra virgin olive oil. Fruits, vegetables and wholegrains were
      a mainstay, and moderate amounts of nuts and seeds, fish, dairy and red wine were
      recommended. The diet encompassed key features of the MD including cuisine,
      biodiversity and sustainability. The MD model preserved traditional dietary
      components likely to elicit health benefits for individuals with chronic
      diseases, even with the adaptation to an Australian multiethnic population.

PMID- 29642559
TI  - 1-(Acylamino)alkylphosphonic Acids-Alkaline Deacylation.
AB  - The alkaline deacylation of a representative series of 1
      (acylamino)alkylphosphonic acids [(AC)-AAP: (AC) = Ac, TFA, Bz; AAP = GlyP, AlaP,
      ValP, PglP and PheP] in an aqueous solution of KOH (2M) was investigated. The
      results suggested a two-stage reaction mechanism with a quick interaction of the
      hydroxyl ion on the carbonyl function of the amide R-C(O)-N(H)- group in the
      first stage, which leads to instant formation of the intermediary acyl-hydroxyl
      adducts of R-C(O-)2-N(H)-, visible in the 31P NMR spectra. In the second stage,
      these intermediates decompose slowly by splitting of the RC(O-)2-N(H)- function
      with the subsequent formation of 1-aminoalkylphosphonate and carboxylate ions.

PMID- 29642562
TI  - Antioxidant Potential of Extracts Obtained from Macro- (Ascophyllum nodosum,
      Fucus vesiculosus and Bifurcaria bifurcata) and Micro-Algae (Chlorella vulgaris
      and Spirulina platensis) Assisted by Ultrasound.
AB  - Background: Natural antioxidants, which can replace synthetic ones due to their
      potential implications for health problems in children, have gained significant
      popularity. Therefore, the antioxidant potential of extracts obtained from three
      brown macroalgae (Ascophyllum nodosum, Fucus vesiculosus and Bifurcaria
      bifurcata) and two microalgae (Chlorella vulgaris and Spirulina platensis) using
      ultrasound-extraction as an innovative and green approach was evaluated. Methods:
      Algal extracts were obtained by ultrasound-assisted extraction using
      water/ethanol (50:50, v:v) as the extraction solvent. The different extracts were
      compared based on their antioxidant potential, measuring the extraction yield,
      the total phenolic content (TPC) and the antioxidant activity. Results: Extracts
      from Ascophyllum nodosum (AN) and Bifurcaria bifurcata (BB) showed the highest
      antioxidant potential compared to the rest of the samples. In particular, BB
      extract presented the highest extraction (35.85 g extract/100 g dry weight (DW))
      and total phenolic compounds (TPC) (5.74 g phloroglucinol equivalents (PGE)/100 g
      DW) yields. Regarding the antioxidant activity, macroalgae showed again higher
      values than microalgae. BB extract had the highest antioxidant activity in the
      ORAC, DPPH and FRAP assays, with 556.20, 144.65 and 66.50 umol Trolox equivalents
      (TE)/g DW, respectively. In addition, a correlation among the antioxidant
      activity and the TPC was noted. Conclusions: Within the obtained extracts,
      macroalgae, and in particular BB, are more suitable to be used as sources of
      phenolic antioxidants to be included in products for human consumption. The
      relatively low antioxidant potential, in terms of polyphenols, of the microalgae
      extracts studied in the present work makes them useless for possible industrial
      applications compared to macroalgae, although further in vivo studies evaluating
      the real impact of antioxidants from both macro- and micro-algae at the cellular
      level should be conducted.

PMID- 29642563
TI  - Application of Multiple Regression and Design of Experiments for Modelling the
      Effect of Monoethylene Glycol in the Calcium Carbonate Scaling Process.
AB  - To avoid gas hydrate formation during oil and gas production, companies usually
      employ thermodynamic inhibitors consisting of hydroxyl compounds, such as
      monoethylene glycol (MEG). However, these inhibitors may cause other types of
      fouling during production such as inorganic salt deposits (scale). Calcium
      carbonate is one of the main scaling salts and is a great concern, especially for
      the new pre-salt wells being explored in Brazil. Hence, it is important to
      understand how using inhibitors to control gas hydrate formation may be
      interacting with the scale formation process. Multiple regression and design of
      experiments were used to mathematically model the calcium carbonate scaling
      process and its evolution in the presence of MEG. It was seen that MEG, although
      inducing the precipitation by increasing the supersaturation ratio, actually
      works as a scale inhibitor for calcium carbonate in concentrations over 40%. This
      effect was not due to changes in the viscosity, as suggested in the literature,
      but possibly to the binding of MEG to the CaCO3 particles' surface. The
      interaction of the MEG inhibition effect with the system's variables was also
      assessed, when temperature' and calcium concentration were more relevant.

PMID- 29642561
TI  - beta-Nicotinamide Adenine Dinucleotide (beta-NAD) Inhibits ATP-Dependent IL-1beta
      Release from Human Monocytic Cells.
AB  - While interleukin-1beta (IL-1beta) is a potent pro-inflammatory cytokine
      essential for host defense, high systemic levels cause life-threatening
      inflammatory syndromes. ATP, a stimulus of IL-1beta maturation, is released from
      damaged cells along with beta-nicotinamide adenine dinucleotide (beta-NAD). Here,
      we tested the hypothesis that beta-NAD controls ATP-signaling and, hence, IL
      1beta release. Lipopolysaccharide-primed monocytic U937 cells and primary human
      mononuclear leukocytes were stimulated with 2'(3')-O-(4-benzoyl-benzoyl)ATP
      trieethylammonium salt (BzATP), a P2X7 receptor agonist, in the presence or
      absence of beta-NAD. IL-1beta was measured in cell culture supernatants. The
      roles of P2Y receptors, nicotinic acetylcholine receptors (nAChRs), and Ca2+
      independent phospholipase A2 (iPLA2beta, PLA2G6) were investigated using specific
      inhibitors and gene-silencing. Exogenous beta-NAD signaled via P2Y receptors and
      dose-dependently (IC50 = 15 uM) suppressed the BzATP-induced IL-1beta release.
      Signaling involved iPLA2beta, release of a soluble mediator, and nAChR subunit
      alpha9. Patch-clamp experiments revealed that beta-NAD inhibited BzATP-induced
      ion currents. In conclusion, we describe a novel triple membrane-passing
      signaling cascade triggered by extracellular beta-NAD that suppresses ATP-induced
      release of IL-1beta by monocytic cells. This cascade links activation of P2Y
      receptors to non-canonical metabotropic functions of nAChRs that inhibit P2X7
      receptor function. The biomedical relevance of this mechanism might be the
      control of trauma-associated systemic inflammation.

PMID- 29642564
TI  - Statistical Multipath Model Based on Experimental GNSS Data in Static Urban
      Canyon Environment.
AB  - A deep understanding of multipath characteristics is essential to design signal
      simulators and receivers in global navigation satellite system applications. As a
      new constellation is deployed and more applications occur in the urban
      environment, the statistical multipath models of navigation signal need further
      study. In this paper, we present statistical distribution models of multipath
      time delay, multipath power attenuation, and multipath fading frequency based on
      the experimental data in the urban canyon environment. The raw data of multipath
      characteristics are obtained by processing real navigation signal to study the
      statistical distribution. By fitting the statistical data, it shows that the
      probability distribution of time delay follows a gamma distribution which is
      related to the waiting time of Poisson distributed events. The fading frequency
      follows an exponential distribution, and the mean of multipath power attenuation
      decreases linearly with an increasing time delay. In addition, the detailed
      statistical characteristics for different elevations and orbits satellites is
      studied, and the parameters of each distribution are quite different. The
      research results give useful guidance for navigation simulator and receiver
      designers.

PMID- 29642565
TI  - Polyacrylonitrile Nanofiber-Based Quartz Crystal Microbalance for Sensitive
      Detection of Safrole.
AB  - Safrole is the main precursor for producing the amphetamine-type stimulant (ATS)
      drug, N-methyl-3,4-methylenedioxyamphetamine (MDMA), also known as ecstasy. We
      devise a polyacrylonitrile (PAN) nanofiber-based quartz crystal microbalance
      (QCM) for detecting safrole. The PAN nanofibers were fabricated by direct
      electrospinning to modify the QCM chips. The PAN nanofiber on the QCM chips has a
      diameter of 240 +/- 10 nm. The sensing of safrole by QCM modified with PAN
      nanofiber shows good reversibility and an apparent sensitivity of 4.6 Hz.L/mg.
      The proposed method is simple, inexpensive, and convenient for detecting safrole,
      and can be an alternative to conventional instrumental analytical methods for
      general volatile compounds.

PMID- 29642566
TI  - In Vitro and In Vivo Osteogenic Activity of Titanium Implants Coated by Pulsed
      Laser Deposition with a Thin Film of Fluoridated Hydroxyapatite.
AB  - To enhance biocompatibility, osteogenesis, and osseointegration, we coated
      titanium implants, by krypton fluoride (KrF) pulsed laser deposition, with a thin
      film of fluoridated hydroxyapatite (FHA). Coating was confirmed by scanning
      electron microscopy (SEM) and scanning probe microscopy (SPM), while
      physicochemical properties were evaluated by attenuated reflectance Fourier
      transform infrared spectroscopy (ATR-FTIR). Calcium deposition, osteocalcin
      production, and expression of osteoblast genes were significantly higher in rat
      bone marrow mesenchymal stem cells seeded on FHA-coated titanium than in cells
      seeded on uncoated titanium. Implantation into rat femurs also showed that the
      FHA-coated material had superior osteoinductive and osseointegration activity in
      comparison with that of traditional implants, as assessed by microcomputed
      tomography and histology. Thus, titanium coated with FHA holds promise as a
      dental implant material.

PMID- 29642567
TI  - Molecular Cloning and Functional Characterization of a Dihydroflavonol 4
      Reductase from Vitis bellula.
AB  - Vitis bellula is a new grape crop in southern China. Berries of this species are
      rich in antioxidative anthocyanins and proanthocyanidins. This study reports
      cloning and functional characterization of a cDNA encoding a V. bellula
      dihydroflavonol reductase (VbDFR) involved in the biosynthesis of anthocyanins
      and proanthocyanidins. A cDNA including 1014 bp was cloned from young leaves and
      its open reading frame (ORF) was deduced encoding 337 amino acids, highly similar
      to V. vinifera DFR (VvDFR). Green florescence protein fusion and confocal
      microscopy analysis determined the cytosolic localization of VbDFR in plant
      cells. A soluble recombinant VbDFR was induced and purified from E. coli for
      enzyme assay. In the presence of NADPH, the recombinant enzyme catalyzed
      dihydrokaempferol (DHK) and dihydroquercetin (DHQ) to their corresponding
      leucoanthocyanidins. The VbDFR cDNA was introduced into tobacco plants via
      Agrobacterium-mediated transformation. The overexpression of VbDFR increased
      anthocyanin production in flowers. Anthocyanin hydrolysis and chromatographic
      analysis revealed that transgenic flowers produced pelargonidin and delphinidin,
      which were not detected in control flowers. These data demonstrated that the
      overexpression of VbDFR produced new tobacco anthocyanidins. In summary, all data
      demonstrate that VbDFR is a useful gene to provide three types of substrates for
      metabolic engineering of anthocyanins and proanthocyanidins in grape crops and
      other crops.

PMID- 29642568
TI  - Irradiation-Induced Cardiac Connexin-43 and miR-21 Responses Are Hampered by
      Treatment with Atorvastatin and Aspirin.
AB  - Radiation of the chest during cancer therapy is deleterious to the heart, mostly
      due to oxidative stress and inflammation related injury. A single sub-lethal dose
      of irradiation has been shown to result in compensatory up-regulation of the
      myocardial connexin-43 (Cx43), activation of the protein kinase C (PKC) signaling
      along with the decline of microRNA (miR)-1 and an increase of miR-21 levels in
      the left ventricle (LV). We investigated whether drugs with antioxidant, anti
      inflammatory or vasodilating properties, such as aspirin, atorvastatin, and
      sildenafil, may affect myocardial response in the LV and right ventricle (RV)
      following chest irradiation. Adult, male Wistar rats were subjected to a single
      sub-lethal dose of chest radiation at 25 Gy and treated with aspirin (3 mg/day),
      atorvastatin (0.25 mg/day), and sildenafil (0.3 mg/day) for six weeks. Cx43,
      PKCepsilon and PKCdelta proteins expression and levels of miR-1 as well as miR-21
      were determined in the LV and RV. Results showed that the suppression of miR-1
      was associated with an increase of total and phosphorylated forms of Cx43 as well
      as PKCepsilon expression in the LV while having no effect in the RV post
      irradiation as compared to the non-irradiated rats. Treatment with aspirin and
      atorvastatin prevented an increase in the expression of Cx43 and PKCepsilon
      without change in the miR-1 levels. Furthermore, treatment with aspirin,
      atorvastatin, and sildenafil completely prevented an increase of miR-21 in the LV
      while having partial effect in the RV post irradiation. The increase in pro
      apoptotic PKCdelta was not affected by any of the used treatment. In conclusion,
      irradiation and drug-induced changes were less pronounced in the RV as compared
      to the LV. Treatment with aspirin and atorvastatin interfered with irradiation
      induced compensatory changes in myocardial Cx43 protein and miR-21 by preventing
      their elevation, possibly via amelioration of oxidative stress and inflammation.

PMID- 29642569
TI  - Holotoxin A1 Induces Apoptosis by Activating Acid Sphingomyelinase and Neutral
      Sphingomyelinase in K562 and Human Primary Leukemia Cells.
AB  - Marine triterpene glycosides are attractive candidates for the development of
      anticancer agents. Holotoxin A1 is a triterpene glycoside found in the edible sea
      cucumber, Apostichopus (Stichopus) japonicus. We previously showed that
      cladoloside C2, the 25(26)-dihydro derivative of holotoxin A1 induced apoptosis
      in human leukemia cells by activating ceramide synthase 6. Thus, we hypothesized
      that holotoxin A1, which is structurally similar to cladoloside C2, might induce
      apoptosis in human leukemia cells through the same molecular mechanism. In this
      paper, we compared holotoxin A1 and cladoloside C2 for killing potency and
      mechanism of action. We found that holotoxin A1 induced apoptosis more potently
      than cladoloside C2. Moreover, holotoxin A1-induced apoptosis in K562 cells by
      activating caspase-8 and caspase-3, but not by activating caspase-9. During
      holotoxin A1-induced apoptosis, acid sphingomyelinase (SMase) and neutral SMase
      were activated in both K562 cells and human primary leukemia cells. Specifically
      inhibiting acid SMase and neutral SMase with chemical inhibitors or siRNAs
      significantly inhibited holotoxin A1-induced apoptosis. These results indicated
      that holotoxin A1 might induce apoptosis by activating acid SMase and neutral
      SMase. In conclusion, holotoxin A1 represents a potential anticancer agent for
      treating leukemia. Moreover, the aglycone structure of marine triterpene
      glycosides might affect the mechanism involved in inducing apoptosis.

PMID- 29642570
TI  - Enhanced Efficacy of High Dose Oral Vancomycin Therapy in Clostridium difficile
      Diarrhea for Hospitalized Adults Not Responsive to Conventional Oral Vancomycin
      Therapy: Antibiotic Stewardship Implications.
AB  - Current therapy of Clostridium difficile diarrhea (CDD) is problematic. Optimal
      treatment for CDD remains oral vancomycin, but there is little data on oral
      vancomycin dosing regimens. The objective of this C. difficile diarrhea study was
      to compare the efficacy of "high dose" vancomycin, 500 mg (PO) q6h, as sole
      treatment and in those who after 72 h failed to respond to conventional doses of
      oral vancomycin, 125-250 mg (PO) q6h. Hospitalized adults with CDD were evaluated
      by various oral vancomycin regimens, i.e., a conventional dose group (125-250 mg
      (PO) q6h), a "high dose escalation" dose group (250 mg -> 500 mg (PO) q6h), and a
      "high dose" group (500 mg (PO) q6h). Oral vancomycin treatment groups were
      compared by time to improvement, i.e., decrease in >50% of watery stools/day and
      duration of therapy. The high dose escalation and high dose oral vancomycin
      groups showed the most rapid resolution of diarrhea. There was marked decrease in
      stools/day after "high dose" vancomycin escalation from conventional dosing,
      i.e., 250 mg (PO) q6h -> 500 mg (PO) q6h. This study demonstrated that "high
      dose" escalation or initial high dose oral vancomycin, i.e., 500 mg (PO) q6h was
      the most efficacious regimen for CDD.

PMID- 29642571
TI  - Ultraviolet Laser Damage Dependence on Contamination Concentration in Fused
      Silica Optics during Reactive Ion Etching Process.
AB  - The reactive ion etching (RIE) process of fused silica is often accompanied by
      surface contamination, which seriously degrades the ultraviolet laser damage
      performance of the optics. In this study, we find that the contamination behavior
      on the fused silica surface is very sensitive to the RIE process which can be
      significantly optimized by changing the plasma generating conditions such as
      discharge mode, etchant gas and electrode material. Additionally, an optimized
      RIE process is proposed to thoroughly remove polishing-introduced contamination
      and efficiently prevent the introduction of other contamination during the
      etching process. The research demonstrates the feasibility of improving the
      damage performance of fused silica optics by using the RIE technique.

PMID- 29642572
TI  - Enhanced CO2 Adsorption by Nitrogen-Doped Graphene Oxide Sheets (N-GOs) Prepared
      by Employing Polymeric Precursors.
AB  - Nitrogen-doped graphene oxide sheets (N-GOs) are prepared by employing N
      containing polymers such as polypyrrole, polyaniline, and copolymer (polypyrrole
      polyaniline) doped with acids such as HCl, H2SO4, and C6H5-SO3-K, which are
      activated using different concentrations of KOH and carbonized at 650  degrees C;
      characterized using SEM, TEM, BET, TGA-DSC, XRD, and XPS; and employed for the
      removal of environmental pollutant CO2. The porosity of the N-GOs obtained were
      found to be in the range 1-3.5 nm when the KOH employed was in the ratio of 1:4,
      and the XRD confirmed the formation of the layered like structure. However, when
      the KOH employed was in the ratio of 1:2, the pore diameter was found to be in
      the range of 50-200 nm. The SEM and TEM analysis reveal the porosity and sheet
      like structure of the products obtained. The nitrogen-doped graphene oxide sheets
      (N-GOs) prepared by employing polypyrrole doped with C6H5-SO3-K were found to
      possess a high surface area of 2870 m2/g. The N-GOs displayed excellent CO2
      capture property with the N-GOs; PPy/Ar-1 displayed ~1.36 mmol/g. The precursor
      employed, the dopant used, and the activation process were found to affect the
      adsorption property of the N-GOs obtained. The preparation procedure is simple
      and favourable for the synthesis of N-GOs for their application as adsorbents in
      greenhouse gas removal and capture.

PMID- 29642573
TI  - 3D Printing of Thermo-Responsive Methylcellulose Hydrogels for Cell-Sheet
      Engineering.
AB  - A possible strategy in regenerative medicine is cell-sheet engineering (CSE),
      i.e., developing smart cell culture surfaces from which to obtain intact cell
      sheets (CS). The main goal of this study was to develop 3D printing via extrusion
      based bioprinting of methylcellulose (MC)-based hydrogels. Hydrogels were
      prepared by mixing MC powder in saline solutions (Na2SO4 and PBS). MC-based
      hydrogels were analyzed to investigate the rheological behavior and thus optimize
      the printing process parameters. Cells were tested in vitro on ring-shaped
      printed hydrogels; bulk MC hydrogels were used for comparison. In vitro tests
      used murine embryonic fibroblasts (NIH/3T3) and endothelial murine cells (MS1),
      and the resulting cell sheets were characterized analyzing cell viability and
      immunofluorescence. In terms of CS preparation, 3D printing proved to be an
      optimal approach to obtain ring-shaped CS. Cell orientation was observed for the
      ring-shaped CS and was confirmed by the degree of circularity of their nuclei:
      cell nuclei in ring-shaped CS were more elongated than those in sheets detached
      from bulk hydrogels. The 3D printing process appears adequate for the preparation
      of cell sheets of different shapes for the regeneration of complex tissues.

PMID- 29642574
TI  - An Organic Solvent-Tolerant Lipase with Both Hydrolytic and Synthetic Activities
      from the Oleaginous Fungus Mortierella echinosphaera.
AB  - Lipase enzymes of the oleaginous fungal group Mortierella are rarely studied.
      However, considering that most commercial lipases are derived from filamentous
      fungal sources, their investigation can contribute to the cost-effective
      development of new biotechnological processes. Here, an extracellular lipase with
      a molecular mass of 30 kDa was isolated from Mortierella echinosphaera CBS 575.75
      and characterized. The purified lipase exhibited an optimal p-nitrophenyl
      palmitate (pNPP)-hydrolyzing activity at 25  degrees C and pH 6.6-7.0 and proved
      to be highly stable at temperatures up to 40  degrees C and under broad pH
      conditions. The enzyme was active under low temperatures, retaining 32.5% of its
      activity at 10  degrees C, and was significantly stable in polar and non-polar
      organic solvents. The Km, Vmax, and kcat for pNPP were 0.336 mM, 30.4 MUM/min,
      and 45.7 1/min for pNPP and 0.333 mM, 36.9 MUM/min, and 55.6 1/min for pNP
      decanoate, respectively. The pNPP hydrolysis was inhibited by Hg2+, N
      bromosuccinimide, and sodium dodecyl sulfate, while ethylenediaminetetraacetic
      acid and metal ions, such as Ca2+, Mg2+, Na+, and K+ enhanced the activity. The
      purified lipase had non-regioselective activity and wide substrate specificity,
      showing a clear preference for medium-chained p-nitrophenyl esters. Besides its
      good transesterification activity, the enzyme appeared as a suitable biocatalyst
      to operate selective esterification reactions to long-chained alkyl esters.
      Adsorption to Accurel MP1000 improved the storage stability of the enzyme at 5 
      degrees C. The immobilized lipase displayed tolerance to a non-aqueous
      environment and was reusable for up to five cycles without significant loss in
      its synthetic and hydrolytic activities. These findings confirm the applicability
      of both the free and the immobilized enzyme preparations in future research.

PMID- 29642575
TI  - Correction: TURDI, M. et al. Trace Elements Contamination and Human Health Risk
      Assessment in Drinking Water from the Agricultural and Pastoral Areas of Bay
      County, Xinjiang, China; Int. J. Environ. Res. Public Health 2016, 13, 938.
AB  - In the original version of our article[...].

PMID- 29642576
TI  - Comment on Cerland, L. et al. Incidence and Consequences of Near-Drowning-Related
      Pneumonia-A Descriptive Series from Martinique, French West Indies. Int. J.
      Environ. Res. Public Health 2017, 14, 1402.
AB  - We read with great interest the recent paper by Cerland et al. on the frequency,
      nature, and consequences of post-drowning pneumonia[...].

PMID- 29642577
TI  - New Analysis Scheme of Flow-Acoustic Coupling for Gas Ultrasonic Flowmeter with
      Vortex near the Transducer.
AB  - Ultrasonic flowmeters with a small or medium diameter are widely used in process
      industries. The flow field disturbance on acoustic propagation caused by a vortex
      near the transducer inside the sensor as well as the mechanism and details of
      flow-acoustic interaction are needed to strengthen research. For that reason, a
      new hybrid scheme is proposed; the theories of computational fluid dynamics
      (CFD), wave acoustics, and ray acoustics are used comprehensively by a new step
      by-step method. The flow field with a vortex near the transducer, and its
      influence on sound propagation, receiving, and flowmeter performance are analyzed
      in depth. It was found that, firstly, the velocity and vortex intensity
      distribution were asymmetric on the sensor cross-section and acoustic path.
      Secondly, when passing through the vortex zone, the central ray trajectory was
      deflected significantly. The sound pressure on the central line of the sound path
      also changed. Thirdly, the pressure deviation becomes larger with as the flow
      velocity increases. The deviation was up to 17% for different velocity profiles
      in a range of 0.6 m/s to 53 m/s. Lastly, in comparison to the theoretical value,
      the relative deviation of the instrument coefficient for the velocity profile
      with a vortex near the transducer reached up to -17%. In addition, the
      rationality of the simulation was proved by experiments.

PMID- 29642578
TI  - Microwave-Assisted Oxalic Acid Pretreatment for the Enhancing of Enzyme
      Hydrolysis in the Production of Xylose and Arabinose from Bagasse.
AB  - In this study, highly-efficient hydrolysis of bagasse into xylose and arabinose
      sugars (C5 sugars) was developed by microwave-assisted oxalic acid pretreatment
      under mild reaction conditions. The effects of acid and hydrolysis conditions on
      the C5 sugar yields were discussed. The results showed that oxalic acid performed
      better than hydrochloric acid and maleic acid, and was a promising alternative to
      sulfuric acid for xylose production at the same acid concentration. The maximum
      yields of xylose (95.7%) and arabinose (91.5%) were achieved via the microwave
      assisted oxalic acid pretreatment (120  degrees C, 10 min, 0.4 mol/L, solid
      liquid ratio of 1:50 g/mL), indicating that almost all xylan-type hemicelluloses
      were released from the cell wall and hydrolyzed into C5 sugars. After
      pretreatment, more than 90% of the cellulose in the residual bagasse was
      converted to glucose (92.2%) by enzymatic hydrolysis. This approach could realize
      the highly-efficient hydrolysis of xylan from bagasse into C5 sugars, which would
      enhance the enzyme hydrolysis of treated bagasse into glucose.

PMID- 29642579
TI  - Dual Effects of Alpha-Hydroxy Acids on the Skin.
AB  - AHAs are organic acids with one hydroxyl group attached to the alpha position of
      the acid. AHAs including glycolic acid, lactic acid, malic acid, tartaric acid,
      and citric acid are often used extensively in cosmetic formulations. AHAs have
      been used as superficial peeling agents as well as to ameliorate the appearance
      of keratoses and acne in dermatology. However, caution should be exercised in
      relation to certain adverse reactions among patients using products with AHAs,
      including swelling, burning, and pruritus. Whether AHAs enhance or decrease photo
      damage of the skin remains unclear, compelling us to ask the question, is AHA a
      friend or a foe of the skin? The aim of this manuscript is to review the various
      biological effects and mechanisms of AHAs on human keratinocytes and in an animal
      model. We conclude that whether AHA is a friend or foe of human skin depends on
      its concentration. These mechanisms of AHAs are currently well understood, aiding
      the development of novel approaches for the prevention of UV-induced skin damage.

PMID- 29642580
TI  - Arbidol (Umifenovir): A Broad-Spectrum Antiviral Drug That Inhibits Medically
      Important Arthropod-Borne Flaviviruses.
AB  - Arthropod-borne flaviviruses are human pathogens of global medical importance,
      against which no effective small molecule-based antiviral therapy has currently
      been reported. Arbidol (umifenovir) is a broad-spectrum antiviral compound
      approved in Russia and China for prophylaxis and treatment of influenza. This
      compound shows activities against numerous DNA and RNA viruses. The mode of
      action is based predominantly on impairment of critical steps in virus-cell
      interactions. Here we demonstrate that arbidol possesses micromolar-level anti
      viral effects (EC50 values ranging from 10.57 +/- 0.74 to 19.16 +/- 0.29 uM) in
      Vero cells infected with Zika virus, West Nile virus, and tick-borne encephalitis
      virus, three medically important representatives of the arthropod-borne
      flaviviruses. Interestingly, no antiviral effects of arbidol are observed in
      virus infected porcine stable kidney cells (PS), human neuroblastoma cells (UKF
      NB-4), and human hepatoma cells (Huh-7 cells) indicating that the antiviral
      effect of arbidol is strongly cell-type dependent. Arbidol shows increasing
      cytotoxicity when tested in various cell lines, in the order: Huh-7 < HBCA < PS <
      UKF-NB-4 < Vero with CC50 values ranging from 18.69 +/- 0.1 to 89.72 +/- 0.19 uM.
      Antiviral activities and acceptable cytotoxicity profiles suggest that arbidol
      could be a promising candidate for further investigation as a potential
      therapeutic agent in selective treatment of flaviviral infections.

PMID- 29642581
TI  - Remnants of an Ancient Deltaretrovirus in the Genomes of Horseshoe Bats
      (Rhinolophidae).
AB  - Endogenous retrovirus (ERV) sequences provide a rich source of information about
      the long-term interactions between retroviruses and their hosts. However, most
      ERVs are derived from a subset of retrovirus groups, while ERVs derived from
      certain other groups remain extremely rare. In particular, only a single ERV
      sequence has been identified that shows evidence of being related to an ancient
      Deltaretrovirus, despite the large number of vertebrate genome sequences now
      available. In this report, we identify a second example of an ERV sequence
      putatively derived from a past deltaretroviral infection, in the genomes of
      several species of horseshoe bats (Rhinolophidae). This sequence represents a
      fragment of viral genome derived from a single integration. The time of the
      integration was estimated to be 11-19 million years ago. This finding, together
      with the previously identified endogenous Deltaretrovirus in long-fingered bats
      (Miniopteridae), suggest a close association of bats with ancient
      deltaretroviruses.

PMID- 29642582
TI  - Synthesis of a Novel Electrospun Polycaprolactone Scaffold Functionalized with
      Ibuprofen for Periodontal Regeneration: An In Vitro andIn Vivo Study.
AB  - Ibuprofen (IBU) has been shown to improve periodontal treatment outcomes. The aim
      of this study was to develop a new anti-inflammatory scaffold by functionalizing
      an electrospun nanofibrous poly-epsilon-caprolactone membrane with IBU (IBU-PCL)
      and to evaluate its impact on periodontal inflammation, wound healing and
      regeneration in vitro and in vivo. IBU-PCL was synthesized through
      electrospinning. The effects of IBU-PCL on the proliferation and migration of
      epithelial cells (EC) and fibroblasts (FB) exposed to Porphyromonas gingivlais
      lipopolysaccharide (Pg-LPS) were evaluated through the AlamarBlue test and
      scratch assay, respectively. Anti-inflammatory and remodeling properties were
      investigated through Real time qPCR. Finally, the in vivo efficacy of the IBU-PCL
      membrane was assessed in an experimental periodontitis mouse model through
      histomorphometric analysis. The results showed that the anti-inflammatory effects
      of IBU on gingival cells were effectively amplified using the functionalized
      membrane. IBU-PCL reduced the proliferation and migration of cells challenged by
      Pg-LPS, as well as the expression of fibronectin-1, collagen-IV, integrin
      alpha3beta1 and laminin-5. In vivo, the membranes significantly improved the
      clinical attachment and IBU-PCL also reduced inflammation-induced bone
      destruction. These data showed that the IBU-PCL membrane could efficiently and
      differentially control inflammatory and migratory gingival cell responses and
      potentially promote periodontal regeneration.

PMID- 29642584
TI  - Antileishmanial Activity of 2-Methoxy-4H-spiro-[naphthalene-1,2'-oxiran]-4-one
      (Epoxymethoxy-lawsone): A Promising New Drug Candidate for Leishmaniasis
      Treatment.
AB  - Epoxymethoxylawsone is a naphthoquinone derivative promising as drug candidate
      for the treatment of leishmaniases. In the present work the effectiveness of
      epoxymethoxylawsone, and meglumine antimoniate on Leishmania (Leishmania)
      amazonensis parasites and on mice paw lesions of infected BALB/c mice was
      assessed. In an intracellular amastigotes assay, the half-maximal inhibitory
      concentration (IC50) value for epoxymethoxylawsone was slightly higher (1.7-fold)
      than that found for meglumine antimoniate. The efficacy of both drugs became more
      evident after 48 h of exposure when either the oxirane compound and reference
      drug reached 18-fold and 7.4-fold lower IC50 values (0.40 +/- 0.001 uM and 0.60
      +/- 0.02 uM), respectively. Promastigotes were also affected by
      epoxymethoxylawsone after 24 h of incubation (IC50 = 45.45 +/- 5.0 uM), but with
      IC50 6-fold higher than those found for intracellular amastigotes. Cytotoxicity
      analysis revealed that epoxymethoxylawsone (CC50 = 40.05 +/- uM) has 1.7-fold
      higher effects than meglumine antimoniate (CC50 = 24.14 +/- 2.6 uM). Treatment of
      the paw lesion in infected BALB/c mice with epoxymethoxy-lawsone led to a
      significant 27% reduction (p < 0.05) of the lesion size, for all administrated
      doses, compared to the control group. Lesion reduction was also detected after
      mice treatment with meglumine antimoniate, reaching 31.0% (0.23 mg of
      Sb(V)/Kg/day and 2.27 mg of Sb(V)/Kg/day) and 64.0% (22.7 mg of Sb(V)/Kg/day). In
      addition, mice lesion ultrastructural changes were evidenced in amastigotes. The
      set of data gathered here indicate that epoxymethoxylawsone has pronounced
      effects on parasites and merits furthering to the preclinical stage.

PMID- 29642583
TI  - Feline APOBEC3s, Barriers to Cross-Species Transmission of FIV?
AB  - The replication of lentiviruses highly depends on host cellular factors, which
      defines their species-specific tropism. Cellular restriction factors that can
      inhibit lentiviral replication were recently identified. Feline immunodeficiency
      virus (FIV) was found to be sensitive to several feline cellular restriction
      factors, such as apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like
      3 (APOBEC3) and tetherin, but FIV evolved to counteract them. Here, we describe
      the molecular mechanisms by which feline APOBEC3 restriction factors inhibit FIV
      replication and discuss the molecular interaction of APOBEC3 proteins with the
      viral antagonizing protein Vif. We speculate that feline APOBEC3 proteins could
      explain some of the observed FIV cross-species transmissions described in wild
      Felids.

PMID- 29642586
TI  - Are Bank Employees Stressed? Job Perception and Positivity in the Banking Sector:
      An Italian Observational Study.
AB  - Background: The epidemiology of stress on bank workers in Europe is only at the
      introductory stages. This study investigated for the first time the association
      between occupational stress level in bank-employees using the BEST8, Karasek
      Model and socio-demographic and working factors in Italy. Methods: The
      observational pilot study involved 384 employees. Three questionnaires were
      adopted to collect data: Karasek-Model, BEST8 (p < 0.001) and Positivity-Scale.
      Results: 25% of the sample belonged to high stress group. The workers more
      stressed were older with a commercial role and consumer of
      antidepressants/sedatives. Women were much more likely to agree with the
      perception of feeling unsafe in a possible robbery (OR = 2.42; 95% CI: 1.50-3.91)
      and with that sales requests were in conflict with one's own personal moral code
      (OR = 2.31; 95% CI: 1.38-3.87). Older employees declared feeling inadequate in
      the workplace (OR = 1.97; 95% CI: 1.07-3.65) and younger employees referred to be
      anxious about meeting financial budget goals. Workers who had a low positivity
      had a lower probability of adaptation (OR = 0.88; 95% CI: 0.83-0.93).
      Conclusions: The occupational stress level in the banking sector involves many
      aspects: gender, type of bank, role, personal morals, high job-demands, low level
      of decision-making. This study recommended that banks should implement strategic
      interventions for well-being of employees, and consequently for their
      productivity.

PMID- 29642585
TI  - Mitochondrial Biogenesis in Diverse Cauliflower Cultivars under Mild and Severe
      Drought. Impaired Coordination of Selected Transcript and Proteomic Responses,
      and Regulation of Various Multifunctional Proteins.
AB  - Mitochondrial responses under drought within Brassica genus are poorly
      understood. The main goal of this study was to investigate mitochondrial
      biogenesis of three cauliflower (Brassica oleracea var. botrytis) cultivars with
      varying drought tolerance. Diverse quantitative changes (decreases in abundance
      mostly) in the mitochondrial proteome were assessed by two-dimensional gel
      electrophoresis (2D PAGE) coupled with liquid chromatography-tandem mass
      spectrometry (LC-MS/MS). Respiratory (e.g., complex II, IV (CII, CIV) and ATP
      synthase subunits), transporter (including diverse porin isoforms) and matrix
      multifunctional proteins (e.g., components of RNA editing machinery) were
      diversely affected in their abundance under two drought levels. Western
      immunoassays showed additional cultivar-specific responses of selected
      mitochondrial proteins. Dehydrin-related tryptic peptides (found in several 2D
      spots) immunopositive with dehydrin-specific antisera highlighted the relevance
      of mitochondrial dehydrin-like proteins for the drought response. The abundance
      of selected mRNAs participating in drought response was also determined. We
      conclude that mitochondrial biogenesis was strongly, but diversely affected in
      various cauliflower cultivars, and associated with drought tolerance at the
      proteomic and functional levels. However, discussed alternative oxidase (AOX)
      regulation at the RNA and protein level were largely uncoordinated due to the
      altered availability of transcripts for translation, mRNA/ribosome interactions,
      and/or miRNA impact on transcript abundance and translation.

PMID- 29642587
TI  - Pervasive Chimerism in the Replication-Associated Proteins of Uncultured Single
      Stranded DNA Viruses.
AB  - Numerous metagenomic studies have uncovered a remarkable diversity of circular
      replication-associated protein (Rep)-encoding single-stranded (CRESS) DNA
      viruses, the majority of which are uncultured and unclassified. Unlike capsid
      proteins, the Reps show significant similarity across different groups of CRESS
      DNA viruses and have conserved domain organization with the N-terminal nuclease
      and the C-terminal helicase domain. Consequently, Rep is widely used as a marker
      for identification, classification and assessment of the diversity of CRESS DNA
      viruses. However, it has been shown that in certain viruses the Rep nuclease and
      helicase domains display incongruent evolutionary histories. Here, we
      systematically evaluated the co-evolutionary patterns of the two Rep domains
      across classified and unclassified CRESS DNA viruses. Our analysis indicates that
      the Reps encoded by members of the families Bacilladnaviridae, Circoviridae,
      Geminiviridae, Genomoviridae, Nanoviridae and Smacoviridae display largely
      congruent evolutionary patterns in the two domains. By contrast, among the
      unclassified CRESS DNA viruses, 71% appear to have chimeric Reps. Such massive
      chimerism suggests that unclassified CRESS DNA viruses represent a dynamic
      population in which exchange of gene fragments encoding the nuclease and helicase
      domains is extremely common. Furthermore, purging of the chimeric sequences
      uncovered six monophyletic Rep groups that may represent new families of CRESS
      DNA viruses.

PMID- 29642588
TI  - Crystal Structure of the Isocitrate Dehydrogenase 2 from Acinetobacter baumannii
      (AbIDH2) Reveals a Novel Dimeric Structure with Two Monomeric-IDH-Like Subunits.
AB  - Monomeric isocitrate dehydrogenases (IDHs) have a single polypeptide sizing
      around 85 kDa. The IDH2 from the opportunistic bacterium Acinetobacter baumannii
      (AbIDH2) with a mass of 83 kDa was formerly recognized as a typical monomeric
      IDH. However, both size exclusion chromatography and analytical
      ultracentrifugation analysis indicated that AbIDH2 exists as a homodimer in
      solution. The crystallographic study of the substrate/coenzyme-free AbIDH2 gave a
      dimeric structure and each subunit contained a domain I and a domain II. The
      dimeric assembly is mainly stabilized by hydrophobic interactions (16 hydrogen
      bonds and 11 salt bridges) from the dimer's interface platform, which centered
      around the three parallel helices (alpha4, alpha12, and alpha17) and one loop
      from the domain II. Kinetic analysis showed that the dimeric AbIDH2 showed much
      lower catalytic efficiency (0.39 MUM-1.s-1) as compared to the typical monomeric
      IDHs (~15 MUM-1.s-1). Key residues crucial for dimer formation were
      simultaneously changed to generate the mutant mAbIDH2. The disruption of the
      hydrophobic forces disassociated the dimeric AbIDH2, making mAbIDH2 a monomeric
      enzyme. mAbIDH2 sustained specific activity (21.9 +/- 2 U/mg) comparable to
      AbIDH2 (25.4 +/- 0.7 U/mg). However, mAbIDH2 proved to be a thermolabile enzyme,
      indicating that the thermostable dimeric AbIDH2 may have a physiological
      significance for the growth and pathogenesis of A. baumannii. Phylogenetic
      analysis demonstrated the existence of numerous AbIDH2 homologous proteins, thus
      expanding the monomeric IDH protein family.

PMID- 29642589
TI  - The Molecular Targets and Anti-Invasive Effects of 2,6-bis-(4-hydroxyl
      3methoxybenzylidine) cyclohexanone or BHMC in MDA-MB-231 Human Breast Cancer
      Cells.
AB  - In order to metastasize, tumor cells need to migrate and invade the surrounding
      tissues. It is important to identify compound(s) capable of disrupting the
      metastasis of invasive cancer cells, especially for hindering invadopodia
      formation, so as to provide anti-metastasis targeted therapy. Invadopodia are
      thought to be specialized actin-rich protrusions formed by highly invasive cancer
      cells to degrade the extracellular matrix (ECM). A curcuminoid analogue known as
      2,6-bis-(4-hydroxy-3-methoxybenzylidine)cyclohexanone or BHMC has shown good
      potential in inhibiting inflammation and hyperalgesia. It also possesses an anti
      tumor effects on 4T1 murine breast cancer cells in vivo. However, there is still
      a lack of empirical evidence on how BHMC works in preventing human breast cancer
      invasion. In this study, we investigated the effect of BHMC on MDA-MB-231 breast
      cancer cells and its underlying mechanism of action to prevent breast cancer
      invasion, especially during the formation of invadopodia. All MDA-MB-231 cells,
      which were exposed to the non-cytotoxic concentrations of BHMC, expressed the
      proliferating cell nuclear antigen (PCNA), which indicate that the anti
      proliferative effects of BHMC did not interfere in the subsequent experiments. By
      using a scratch migration assay, transwell migration and invasion assays, we
      determined that BHMC reduces the percentage of migration and invasion of MDA-MB
      231 cells. The gelatin degradation assay showed that BHMC reduced the number of
      cells with invadopodia. Analysis of the proteins involved in the invasion showed
      that there is a significant reduction in the expressions of Rho guanine
      nucleotide exchange factor 7 (beta-PIX), matrix metalloproteinase-9 (MMP-9), and
      membrane type 1 matrix metalloproteinase (MT1-MMP) in the presence of BHMC
      treatment at 12.5 uM. Therefore, it can be postulated that BHMC at 12.5 uM is the
      optimal concentration for preventing breast cancer invasion.

PMID- 29642590
TI  - Characterizing Phage Genomes for Therapeutic Applications.
AB  - Multi-drug resistance is increasing at alarming rates. The efficacy of phage
      therapy, treating bacterial infections with bacteriophages alone or in
      combination with traditional antibiotics, has been demonstrated in emergency
      cases in the United States and in other countries, however remains to be approved
      for wide-spread use in the US. One limiting factor is a lack of guidelines for
      assessing the genomic safety of phage candidates. We present the phage
      characterization workflow used by our team to generate data for submitting phages
      to the Federal Drug Administration (FDA) for authorized use. Essential analysis
      checkpoints and warnings are detailed for obtaining high-quality genomes,
      excluding undesirable candidates, rigorously assessing a phage genome for safety
      and evaluating sequencing contamination. This workflow has been developed in
      accordance with community standards for high-throughput sequencing of viral
      genomes as well as principles for ideal phages used for therapy. The feasibility
      and utility of the pipeline is demonstrated on two new phage genomes that meet
      all safety criteria. We propose these guidelines as a minimum standard for phages
      being submitted to the FDA for review as investigational new drug candidates.

PMID- 29642591
TI  - Light Emission from the Fe2+-EGTA-H2O2 System: Possible Application for the
      Determination of Antioxidant Activity of Plant Phenolics.
AB  - Oxidative reactions can result in the formation of electronically excited species
      that undergo radiative decay depending on electronic transition from the excited
      state to the ground state with subsequent ultra-weak photon emission (UPE). We
      investigated the UPE from the Fe2+-EGTA (ethylene glycol-bis(beta-aminoethyl
      ether)-N,N,N',N'-tetraacetic acid)-H2O2 system with a multitube luminometer
      (Peltier-cooled photon counter, spectral range 380 to 630 nm). The UPE of 92.6
      umol/L Fe2+-185.2 umol/L EGTA-2.6 mmol/L H2O2 reached 4319 +/- 755 relative light
      units during 2 min measurement and was about seven times higher (p < 0.001) than
      the UPE of incomplete systems (Fe2+-H2O2, EGTA-H2O2) and medium alone.
      Substitution of Fe2+ with Cr2+, Co2+, Mn2+ or Cu2+ as well as of EGTA with EDTA
      (ethylenediaminetetraacetic acid) or citrate completely abolished UPE.
      Experiments with ROS scavengers revealed the dependence of UPE on hydroxyl
      radicals suggesting occurrence of oxidative attack and cleavage of the ether bond
      in EGTA backbone structure and formation of triplet excited carbonyl groups with
      subsequent light emission. Plant phenolics (ferulic, chlorogenic and caffec
      acids) at concentration 87 umol/L and ascorbate at 0.46 mmol/L inhibited UPE by
      90 +/- 4%, 90 +/- 5%, 97 +/- 2% and 92 +/- 1%, respectively. Quenching of UPE
      from Fe2+-EGTA-H2O2 system can be used for evaluation of antioxidant activity of
      phytochemicals.

PMID- 29642592
TI  - The Effects of Long-Term, Low- and High-Dose Beta-Carotene Treatment in Zucker
      Diabetic Fatty Rats: The Role of HO-1.
AB  - Nowadays, there is a growing interest in compounds derived from plants as
      potential raw materials for drug development. One of the most studied compounds
      is beta-carotene (BC). Several clinical studies can be found investigating the
      cardiovascular effects of BC, however, all these results are controversial. There
      is an increasing body of evidence showing that besides the well-known antioxidant
      properties, under strong oxidative circumstances, BC could become prooxidant as
      well. In this study, we investigated the effects of long-term, low- and high-dose
      BC treatment in ischemic/reperfused (ISA/REP) hearts isolated from Zucker
      diabetic fatty (ZDF) rats. The animals were treated with various daily doses of
      BC for 4 weeks and then hearts were isolated and subjected to 30 min of global
      ischemia (ISA) followed by 120 min of reperfusion (REP). Blood glucose levels
      were measured before, after two weeks, and at the end of the treatment. In
      isolated hearts, the myocardial function was registered. At the end of the
      reperfusion period, the infarct size (IS) and heme oxygenase-1 (HO-1) expression
      were measured. The results showed that a low dose of BC treatment significantly
      improved postischemic recovery, which was reflected in a decreased IS.
      Interestingly, when BC was applied at high concentrations, the observed
      protective effects were lost. Although BC treatment increased HO-1 expression, we
      did not observe a better heart function and/or decreased IS in the high-dose
      treated group. Glucose tolerance tests showed a concentration-independent
      decrease in blood glucose levels. Our results suggest that long-term, low-dose BC
      treatment could be effective in the treatment of type-2-diabetes and related
      cardiovascular diseases.

PMID- 29642593
TI  - Measuring the Human Ultra-Weak Photon Emission Distribution Using an Electron
      Multiplying, Charge-Coupled Device as a Sensor.
AB  - Ultra-weak photon emission (UPE) is the spontaneous emission from living systems
      mainly attributed to oxidation reactions, in which reactive oxygen species (ROS)
      may play a major role. Given the capability of the next-generation electron
      multiplying CCD (EMCCD) sensors and the easy use of liquid crystal tunable
      filters (LCTF), the aim of this work was to explore the potential of a simple UPE
      spectrometer to measure the UPE from a human hand. Thus, an easy setup was
      configured based on a dark box for inserting the subject's hand prior to LCTF as
      a monochromator and an EMCCD sensor working in the full vertical binning mode
      (FVB) as a spectra detector. Under controlled conditions, both dark signals and
      left hand UPE were acquired by registering the UPE intensity at different
      selected wavelengths (400, 450, 500, 550, 600, 650, and 700 nm) during a period
      of 10 min each. Then, spurious signals were filtered out by ignoring the pixels
      whose values were clearly outside of the Gaussian distribution, and the dark
      signal was subtracted from the subject hand signal. The stepped spectrum with a
      peak of approximately 880 photons at 500 nm had a shape that agreed somewhat with
      previous reports, and agrees with previous UPE research that reported UPE from
      420 to 570 nm, or 260 to 800 nm, with a range from 1 to 1000 photons s-1 cm-2.
      Obtaining the spectral distribution instead of the total intensity of the UPE
      represents a step forward in this field, as it may provide extra information
      about a subject's personal states and relationship with ROS. A new generation of
      CCD sensors with lower dark signals, and spectrographs with a more uniform
      spectral transmittance, will open up new possibilities for configuring measuring
      systems in portable formats.

PMID- 29642595
TI  - delta-Generalized Labeled Multi-Bernoulli Filter Using Amplitude Information of
      Neighboring Cells.
AB  - The amplitude information (AI) of echoed signals plays an important role in radar
      target detection and tracking. A lot of research shows that the introduction of
      AI enables the tracking algorithm to distinguish targets from clutter better and
      then improves the performance of data association. The current AI-aided tracking
      algorithms only consider the signal amplitude in the range-azimuth cell where
      measurement exists. However, since radar echoes always contain backscattered
      signals from multiple cells, the useful information of neighboring cells would be
      lost if directly applying those existing methods. In order to solve this issue, a
      new delta-generalized labeled multi-Bernoulli (delta-GLMB) filter is proposed. It
      exploits the AI of radar echoes from neighboring cells to construct a united
      amplitude likelihood ratio, and then plugs it into the update process and the
      measurement-track assignment cost matrix of the delta-GLMB filter. Simulation
      results show that the proposed approach has better performance in target's state
      and number estimation than that of the delta-GLMB only using single-cell AI in
      low signal-to-clutter-ratio (SCR) environment.

PMID- 29642594
TI  - Allosteric Activation of GDP-Bound Ras Isoforms by Bisphenol Derivative
      Plasticisers.
AB  - The protein family of small GTPases controls cellular processes by acting as a
      binary switch between an active and an inactive state. The most prominent family
      members are H-Ras, N-Ras, and K-Ras isoforms, which are highly related and
      frequently mutated in cancer. Bisphenols are widespread in modern life because of
      their industrial application as plasticisers. Bisphenol A (BPA) is the best-known
      member and has gained significant scientific as well as public attention as an
      endocrine disrupting chemical, a fact that eventually led to its replacement.
      However, compounds used to replace BPA still contain the molecular scaffold of
      bisphenols. BPA, BPAF, BPB, BPE, BPF, and an amine-substituted BPAF-derivate all
      interact with all GDP-bound Ras-Isoforms through binding to a common site on
      these proteins. NMR-, SOScat-, and GDI- assay-based data revealed a new bisphenol
      induced, allosterically activated GDP-bound Ras conformation that define these
      plasticisers as Ras allosteric agonists.

PMID- 29642596
TI  - Predictors and Barriers to Full Vaccination among Children in Ethiopia.
AB  - Predictors of immunization status outside of large cities in Ethiopia are not
      well known, and Muslims have lower vaccination coverage. The aim of this study is
      to assess factors associated with full immunization among children 12-23 months
      in Worabe, Ethiopia, a Muslim-majority community. A cross-sectional study is
      conducted in summer 2016. Multivariable logistic regression was used to assess
      the significance of predictors of full immunization. Among 484 children, 61% are
      fully vaccinated. Children whose mothers had fewer antenatal care (ANC) visits
      have decreased odds of full vaccination (zero visits: odds ratio (OR) = 0.09; one
      visit: OR = 0.15; two visits: OR = 0.46; three visits: OR = 0.89). The most
      common reasons that the mother gave for not vaccinating the child are fear of
      side reactions (36%), being too busy (31%), or hearing rumors about vaccines
      (28%). Local interventions incorporating interventions with religious authorities
      could raise awareness in the community of the importance of childhood
      immunizations and ANC visits.

PMID- 29642597
TI  - Immune Response against ALK in Children with ALK-Positive Anaplastic Large Cell
      Lymphoma.
AB  - Patients with anaplastic lymphoma kinase (ALK)-positive anaplastic large cell
      lymphoma (ALCL) mount a humoral and cellular immune response against ALK. More
      than 90% of children and adolescents with ALK-positive ALCL have detectable anti
      ALK antibodies in serum or plasma, and the antibody titer inversely correlates
      with the risk of relapse. ALK-specific CD8 and CD4 T cell responses have been
      described in patients with ALK-positive ALCL. Vaccination with ALK DNA led to
      protection against lymphoma growth in a murine model. Collectively, these data
      suggest that the ALK-specific immune response is involved in the control of the
      disease. The characteristics of the humoral and cellular immune response against
      ALK as well as tumor immune escape mechanisms have been increasingly
      investigated. However, tumor and host factors contributing to the individual
      immune response against ALK are still largely unknown. Depending on the
      individual strength of the immune response and its determinants, individualized
      immunological approaches might be appropriate for the consolidation of ALCL
      patients. Strategies such as ALK vaccination could be effective for those with a
      pre-existing anti-tumor immunity, while an allogeneic blood stem cell
      transplantation or check-point inhibition could be effective for others.

PMID- 29642600
TI  - Erratum: Long-Term Dexamethasone Exposure Down-Regulates Hepatic TFR1 and Reduces
      Liver Iron Concentration in Rats; Nutrients 2017, 9, 617.
AB  - The Editorial Office of Nutrients would like to report an error in the published
      paper [1] [...].

PMID- 29642599
TI  - Many Infants and Young Children Are Not Compliant with Mexican and International
      Complementary Feeding Recommendations for Milk and Other Beverages.
AB  - Mexican and international authorities provide guidelines for milk and beverage
      consumption for young children. This study classifies beverages as appropriate or
      inappropriate by age (0-5.9, 6-11.9, and 12-23.9 months) and details consumption
      patterns, amounts consumed, and the associated socio-demographic characteristics.
      Analysis of the Mexican National Nutrition and Health Survey (ENSANUT 2012) was
      conducted (n = 949). Among 0-5.9 month olds, 66.7% consumed either breast milk,
      infant formula, or a combination with no other beverages, whereas 29.3% consumed
      breast milk and/or infant formula with water (mean = 58 g/day) and/or other
      beverages (mean = 115 g/day), such as 100% fruit juice, milk, and sugar-sweetened
      beverages (SSBs). For infants 6-11.9 months, appropriate beverages include breast
      milk, infant formula, and water; only 40.2% met these recommendations. Many 6
      11.9 month olds consumed age-inappropriate beverages, including milk (31%) and
      SSBs (35%). After 12 months of age, appropriate beverages include water, milk,
      and a limited amount of 100% fruit juice and SSBs; 32.4% complied fully, 18.3%
      consumed appropriate and inappropriate beverages, and 49.3% consumed only
      inappropriate beverages. Among 12-23.9 month olds, 58% consumed milk, 18% juice,
      and 42% water while 63% consumed SSBs. Many infants and young children are not
      compliant with Mexican and international breastfeeding and complementary feeding
      guidelines for beverages. Communication and guidance about age-appropriate
      beverages should be improved.

PMID- 29642598
TI  - ALK in Neuroblastoma: Biological and Therapeutic Implications.
AB  - Neuroblastoma (NB) is the most common and deadly solid tumour in children.
      Despite the development of new treatment options for high-risk NB, over half of
      patients relapse and five-year survival remains at 40-50%. Therefore, novel
      treatment strategies aimed at providing long-term disease remission are urgently
      sought. ALK, encoding the anaplastic lymphoma kinase receptor, is altered by gain
      of-function point mutations in around 14% of high-risk NB and represents an ideal
      therapeutic target given its low or absent expression in healthy tissue
      postnatally. Small-molecule inhibitors of Anaplastic Lymphoma Kinase (ALK)
      approved in ALK fusion-positive lung cancer are currently undergoing clinical
      assessment in patients with ALK-mutant NB. Parallel pre-clinical studies are
      demonstrating the efficacy of ALK inhibitors against common ALK variants in NB;
      however, a complex picture of therapeutic resistance is emerging. It is
      anticipated that long-term use of these compounds will require combinatorial
      targeting of pathways downstream of ALK, functionally-related 'bypass' mechanisms
      and concomitant oncogenic pathways.

PMID- 29642601
TI  - N-Confused Porphyrin Immobilized on Solid Supports: Synthesis and Metal Ions
      Sensing Efficacy.
AB  - In this work, the N-confused porphyrin 5,10,15,20-tetraphenyl-2-aza-21
      carbaporphyrin (NCTPP) was immobilized on neutral or cationic supports based on
      silica and on Merrifield resin. The new materials were characterized by
      appropriate techniques (UV-Vis spectroscopy, SEM, and zeta potential analysis).
      Piezoelectric quartz crystal gold electrodes were coated with the different
      hybrids and their ability to interact with heavy metals was evaluated. The
      preliminary results obtained showed that the new materials can be explored for
      metal cations detection and the modification of the material surface is a key
      factor in tuning the metal selectivity.

PMID- 29642602
TI  - Production of Flocculants, Adsorbents, and Dispersants from Lignin.
AB  - Currently, lignin is mainly produced in pulping processes, but it is considered
      as an under-utilized chemical since it is being mainly used as a fuel source.
      Lignin contains many hydroxyl groups that can participate in chemical reactions
      to produce value-added products. Flocculants, adsorbents, and dispersants have a
      wide range of applications in industry, but they are mainly oil-based chemicals
      and expensive. This paper reviews the pathways to produce water soluble lignin
      based flocculants, adsorbents, and dispersants. It provides information on the
      recent progress in the possible use of these lignin-based flocculants,
      adsorbents, and dispersants. It also critically discusses the advantages and
      disadvantages of various approaches to produce such products. The challenges
      present in the production of lignin-based flocculants, adsorbents, and
      dispersants and possible scenarios to overcome these challenges for commercial
      use of these products in industry are discussed.

PMID- 29642603
TI  - Acyclovir-Loaded Chitosan Nanospheres from Nano-Emulsion Templating for the
      Topical Treatment of Herpesviruses Infections.
AB  - Acyclovir is not a good candidate for passive permeation since its polarity and
      solubility limit is partitioning into the stratum corneum. This work aims to
      develop a new topical formulation for the acyclovir delivery. New chitosan
      nanospheres (NS) were prepared by a modified nano-emulsion template method.
      Chitosan NS were characterized by Dynamic Light Scattering (DLS), Transmission
      Electron Microscopy (TEM), and an in vitro release study. The in vitro skin
      permeation experiment was carried out using Franz cells and was equipped with
      porcine skin. Biological studies were performed on the Vero cell line infected by
      HSV-1 and HSV-2 strains. The acyclovir loaded chitosan NS appeared with a
      spherical shape, a size of about 200 nm, and a negative zeta potential of about
      40.0 mV. The loading capacity of the drug was about 8.5%. In vitro release
      demonstrated that the percentage of acyclovir delivered from the nanospheres was
      approximately 30% after six hours. The in vitro skin permeation studies confirmed
      an improved amount of permeated acyclovir. The acyclovir-NS complex displayed a
      higher antiviral activity than that of free acyclovir against both the HSV-1 and
      the HSV-2 strain. The acyclovir-loaded NS showed no anti-proliferative activity
      and no signs of cytotoxicity induced by NS was detected. Confocal laser scanning
      microscopy confirmed that the NS are taken up by the cells.

PMID- 29642604
TI  - Assessment of Ab Initio and Density Functional Theory Methods for the Excitations
      of Donor-Acceptor Complexes: The Case of the Benzene-Tetracyanoethylene Model.
AB  - The understanding of the excited-state properties of electron donors, acceptors
      and their interfaces in organic optoelectronic devices is a fundamental issue for
      their performance optimization. In order to obtain a balanced description of the
      different excitation types for electron-donor-acceptor systems, including the
      singlet charge transfer (CT), local excitations, and triplet excited states,
      several ab initio and density functional theory (DFT) methods for excited-state
      calculations were evaluated based upon the selected model system of benzene
      tetracyanoethylene (B-TCNE) complexes. On the basis of benchmark calculations of
      the equation-of-motion coupled-cluster with single and double excitations method,
      the arithmetic mean of the absolute errors and standard errors of the electronic
      excitation energies for the different computational methods suggest that the M11
      functional in DFT is superior to the other tested DFT functionals, and time
      dependent DFT (TDDFT) with the Tamm-Dancoff approximation improves the accuracy
      of the calculated excitation energies relative to that of the full TDDFT. The
      performance of the M11 functional underlines the importance of kinetic energy
      density, spin-density gradient, and range separation in the development of novel
      DFT functionals. According to the TDDFT results, the performances of the
      different TDDFT methods on the CT properties of the B-TCNE complexes were also
      analyzed.

PMID- 29642605
TI  - Abundances of Clinically Relevant Antibiotic Resistance Genes and Bacterial
      Community Diversity in the Weihe River, China.
AB  - The spread of antibiotic resistance genes in river systems is an emerging
      environmental issue due to their potential threat to aquatic ecosystems and
      public health. In this study, we used droplet digital polymerase chain reaction
      (ddPCR) to evaluate pollution with clinically relevant antibiotic resistance
      genes (ARGs) at 13 monitoring sites along the main stream of the Weihe River in
      China. Six clinically relevant ARGs and a class I integron-integrase (intI1) gene
      were analyzed using ddPCR, and the bacterial community was evaluated based on the
      bacterial 16S rRNA V3-V4 regions using MiSeq sequencing. The results indicated
      Proteobacteria, Actinobacteria, Cyanobacteria, and Bacteroidetes as the dominant
      phyla in the water samples from the Weihe River. Higher abundances of blaTEM,
      strB, aadA, and intI1 genes (103 to 105 copies/mL) were detected in the surface
      water samples compared with the relatively low abundances of strA, mecA, and vanA
      genes (0-1.94 copies/mL). Eight bacterial genera were identified as possible
      hosts of the intI1 gene and three ARGs (strA, strB, and aadA) based on network
      analysis. The results suggested that the bacterial community structure and
      horizontal gene transfer were associated with the variations in ARGs.

PMID- 29642606
TI  - Metabolism-Driven High-Throughput Cancer Identification with GLUT5-Specific
      Molecular Probes.
AB  - Point-of-care applications rely on biomedical sensors to enable rapid detection
      with high sensitivity and selectivity. Despite advances in sensor development,
      there are challenges in cancer diagnostics. Detection of biomarkers, cell
      receptors, circulating tumor cells, gene identification, and fluorescent tagging
      are time-consuming due to the sample preparation and response time involved.
      Here, we present a novel approach to target the enhanced metabolism in breast
      cancers for rapid detection using fluorescent imaging. Fluorescent analogs of
      fructose target the fructose-specific transporter GLUT5 in breast cancers and
      have limited to no response from normal cells. These analogs demonstrate a marked
      difference in adenocarcinoma and premalignant cells leading to a novel detection
      approach. The vastly different uptake kinetics of the analogs yields two unique
      signatures for each cell type. We used normal breast cells MCF10A, adenocarcinoma
      cells MCF7, and premalignant cells MCF10AneoT, with hepatocellular carcinoma
      cells HepG2 as the negative control. Our data indicated that MCF10AneoT and MCF7
      cells had an observable difference in response to only one of the analogs. The
      response, observed as fluorescence intensity, leads to a two-point assessment of
      the cells in any sample. Since the treatment time is 10 min, there is potential
      for use in rapid on-site high-throughput diagnostics.

PMID- 29642607
TI  - A New Inflammatory Marker: Elevated Monocyte to HDL Cholesterol Ratio Associated
      with Smoking.
AB  - OBJECTIVES: The adverse effects of smoking in various pathologies are mediated by
      its effects on the inflammatory system. The monocyte to high-density lipoprotein
      cholesterol (HDL-C) ratio (MHR) has recently emerged as an indicator of
      inflammation. We aimed to investigate the relationship between MHR and cigarette
      smoking. PATIENTS AND METHODS: Three hundred and ninety seven consecutive
      participants who smoke and 515 healthy subjects with no history of smoking
      enrolled in the study. Complete blood count parameters and lipid profile were
      analyzed in all study participants. Smoking habits were calculated as pack.years
      and number of cigarettes smoked per day. RESULTS: MHR levels were significantly
      higher in smokers compared to non-smokers (respectively, 15.71 (12.02-20.00) and
      11.17 (8.50-14.16), p < 0.0001)). Pearson's correlation analysis revealed a weak
      but positive correlation between pack.year and MHR in the smokers group, and
      there was a moderate positive correlation between the number of cigarettes smoked
      daily and MHR in the group. In receiver operating characteristics (ROC) analyses,
      it was determined that a MHR value >13.00 measured in smoker participants at
      application had a predictive specificity of 66.6% and sensitivity of 70.0% for
      smoking (area under the curve [AUC] 0.729, 95% CI 0.696, 0.762; p < 0.0001).
      CONCLUSIONS: Elevated MHR is associated with cigarette smoking and may be a
      useful indicator of a systemic inflammatory response in smokers. Smoker
      participants who have high MHR levels can easily be identified during routine
      complete blood count (CBC) analysis and could possibly benefit from preventive
      treatment.

PMID- 29642608
TI  - Neuroprotective Effects of Four Phenylethanoid Glycosides on H2O2-Induced
      Apoptosis on PC12 Cells via the Nrf2/ARE Pathway.
AB  - Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor
      against oxidative stress and neurodegenerative disorders. Phenylethanoid
      glycosides (PhGs; salidroside, acteoside, isoacteoside, and echinacoside) exhibit
      antioxidant and neuroprotective bioactivities. This study was performed to
      investigate the neuroprotective effect and molecular mechanism of PhGs. PhGs
      pretreatment significantly suppressed H2O2-induced cytotoxicity in PC12 cells by
      triggering the nuclear translocation of Nrf2 and reversing the downregulated
      protein expression of heme oxygenase 1 (HO-1), NAD(P)H quinone oxidoreductase 1
      (NQO1), glutamate cysteine ligase-catalytic subunit (GCLC), and glutamate
      cysteine ligase modifier subunit (GCLM). Nrf2 siRNA or HO-1 inhibitor zinc
      protoporphyrin (ZnPP) reduced the neuroprotective effect. PhGs showed potential
      interaction with the Nrf2 binding site in Kelch-like ECH-association protein 1
      (Keap1). This result may support the hypothesis that PhGs are activators of Nrf2.
      We demonstrated the potential binding between PhGs and the Keap1-activated
      Nrf2/ARE pathway, and that PhGs with more glycosides had enhanced effects.

PMID- 29642609
TI  - Pseudogymnoascus destructans: Causative Agent of White-Nose Syndrome in Bats Is
      Inhibited by Safe Volatile Organic Compounds.
AB  - White-nose syndrome (WNS) is caused by Pseudogymnoascus destructans, a
      psychrophilic fungus that infects hibernating bats and has caused a serious
      decline in some species. Natural aroma compounds have been used to control growth
      of fungal food storage pathogens, so we hypothesized that a similar strategy
      could work for control of P. destructans. The effectiveness of exposure to low
      concentrations of the vapor phase of four of these compounds was tested on
      mycelial plugs and conidiospores at temperatures of 5, 10 and 15  degrees C. Here
      we report the efficacy of vapor phase mushroom alcohol (1-octen-3-ol) for
      inhibiting mycelial and conidiospore growth of P. destructans at 0.4 and 0.8
      umol/mL and demonstrate that the R enantiomer of this compound is more effective
      than the S enantiomer, supporting the finding that biological systems can be
      sensitive to stereochemistry. Further, we report that vapor phase leaf aldehyde
      (trans-2-hexenal), a common aroma compound associated with cut grass odors and
      also the major volatile compound in extra virgin olive oil, is more effective
      than mushroom alcohol. At 0.05 umol/mL, trans-2-hexenal is fungicidal to both
      conidiospores and mycelia of P. destructans.

PMID- 29642610
TI  - Don't Know Much about Bumblebees?-A Study about Secondary School Students'
      Knowledge and Attitude Shows Educational Demand.
AB  - Many insects are threatened with extinction, which in the case of pollinating
      insects could lead to declining pollination services and reduced ecosystem
      biodiversity. This necessitates rethinking how we deal with nature in general.
      Schools are ideal places in which to instill a willingness to behave in an
      environmentally-friendly way. Whereas scientific studies and school textbooks
      stress the importance of honeybees as pollinators, the role of bumblebees is
      either underestimated or neglected. The aim of this study was to provide
      information concerning student knowledge and attitudes, which are important
      factors of an individual's environmental awareness. A questionnaire with closed
      and open questions was developed, which also included drawing and species
      identification tasks. We surveyed 870 German secondary school students between 9
      and 20 years of age. Our results indicate limited knowledge of bumblebees by
      students of all grades. Knowledge increased with higher grades but only with a
      small effect size. The attitude of students towards bumblebees was generally
      positive; however, this positivity declined with increasing grade of the
      participants. This correlation also had a small effect size. Our results are
      discussed, with a particular focus on future educational demand.

PMID- 29642611
TI  - Association between Precipitation and Diarrheal Disease in Mozambique.
AB  - Diarrheal diseases are a leading cause of morbidity and mortality in Africa.
      Although research documents the magnitude and pattern of diarrheal diseases are
      associated with weather in particular locations, there is limited quantification
      of this association in sub-Saharan Africa and no studies conducted in Mozambique.
      Our study aimed to determine whether variation in diarrheal disease was
      associated with precipitation in Mozambique. In secondary analyses we
      investigated the associations between temperature and diarrheal disease. We
      obtained weekly time series data for weather and diarrheal disease aggregated at
      the administrative district level for 1997-2014. Weather data include modeled
      estimates of precipitation and temperature. Diarrheal disease counts are
      confirmed clinical episodes reported to the Mozambique Ministry of Health (n =
      7,315,738). We estimated the association between disease counts and
      precipitation, defined as the number of wet days (precipitation > 1 mm) per week,
      for the entire country and for Mozambique's four regions. We conducted time
      series regression analyses using an unconstrained distributed lag Poisson model
      adjusted for time, maximum temperature, and district. Temperature was similarly
      estimated with adjusted covariates. Using a four-week lag, chosen a priori,
      precipitation was associated with diarrheal disease. One additional wet day per
      week was associated with a 1.86% (95% CI: 1.05-2.67%), 1.37% (95% CI: 0.70
      2.04%), 2.09% (95% CI: 1.01-3.18%), and 0.63% (95% CI: 0.11-1.14%) increase in
      diarrheal disease in Mozambique's northern, central, southern, and coastal
      regions, respectively. Our study indicates a strong association between diarrheal
      disease and precipitation. Diarrheal disease prevention efforts should target
      areas forecast to experience increased rainfall. The burden of diarrheal disease
      may increase with increased precipitation associated with climate change, unless
      additional health system interventions are undertaken.

PMID- 29642612
TI  - Ponseti Technique for the Management of Congenital Talipes Equinovarus in a Rural
      Set-Up in India: Experience of 356 Patients.
AB  - Congenital talipes equinovarus (CTEV), also known as clubfoot, is a complex
      congenital deformity of the foot that, left untreated, can limit a person's
      mobility by making it difficult and painful to walk. Worldwide, 80% of children
      born with clubfoot are in low- and middle-income countries. The management of
      clubfoot has a long history. Non-operative management did not become popular, as
      an increasing number of orthopaedists started leaning towards surgical treatment.
      The late Dr. Ignacio Ponseti developed a method of clubfoot correction that
      successfully realigns clubfoot in infants without extensive and major surgery.
      The aim of the study was to assess the functional outcome of CTEV management by
      the Ponseti technique, to study the severity of CTEV deformity using the Pirani
      score, and to evaluate the cost-effectiveness of the technique. A total of 356
      cases with 402 feet with CTEV were treated by the Ponseti method. The average age
      of the children and the number of casts applied before full correction were 4.03
      months and 6.91, respectively. There was a good functional outcome in 95.45% of
      cases (score > 30) at the last follow up. The management of CTEV by the Ponseti
      technique provides a good functional and cosmetic outcome. In a developing
      country like India, this technique is a safe, easy, economical method of clubfoot
      management.

PMID- 29642613
TI  - Effect of Weight on the Resonant Tuning of Energy Harvesting Devices Using Giant
      Magnetostrictive Materials.
AB  - This study deals with the numerical and experimental study of the effect of
      weight on the resonant tuning and energy harvesting characteristics of energy
      harvesting devices using giant magnetostrictive materials. The energy harvesting
      device is made in a cantilever shape using a thin Terfenol-D layer, stainless
      steel (SUS) layer and a movable proof mass, among other things. In this study,
      two types of movable proof mass were prepared, and the device was designed to
      adjust its own resonant frequency automatically to match external vibration
      frequency in real time. Three-dimensional finite element analysis (FEA) was
      performed, and the resonant frequency, tip displacement, and output voltage in
      the devices were predicted and measured, and the simulation and experiment
      results were compared. The effects of the weight of the proof mass on self-tuning
      ability and time-varying behavior were then considered in particular.

PMID- 29642614
TI  - Microfluidic Fabrication of Morphology-Controlled Polymeric Microspheres of
      Blends of Poly(4-butyltriphenylamine) and Poly(methyl methacrylate).
AB  - Multicomponent polymer particles with specific morphology are promising materials
      exhibiting novel functionality which cannot be obtained with single-component
      polymer particles. Particularly, the preparation of such kinds of polymer
      particles involving electrically or optically active conjugated polymers with
      uniform size is a challenging subject due to their intense demands. Here,
      microspheres of binary polymer blend consisting of poly(4-butyltriphenylamine)
      (PBTPA)/poly(methyl methacrylate) (PMMA) (1:1 in weight) were produced via a
      microfluidic emulsification with a Y-shaped microreactor, and a subsequent
      solvent evaporation method. The flow rate of the dispersed phase (polymer
      solution) was fixed to 7 uL/min, and 140 or 700 uL/min of the flow rate of the
      continuous phase (aqueous 0.6 wt % of poly(vinyl alcohol) (PVA) solution) was
      utilized to produce the dispersion with different diameter. The concentration of
      dispersed phase was adjusted to 0.1 or 1.0 w/v%. Core-shell, Janus and dumbbell
      type microspheres were obtained dependent on the flow rate of continuous phase.
      Incomplete core-shell type microspheres were produced for the blend involving low
      molecular weight PMMA. Complex Janus and core-shell type microspheres were
      fabricated by the addition of sodium dodecyl sulfate (SDS) to continuous phase.
      It is found that final morphologies are strongly dependent on the initial
      conditions of dispersion including the particle size suggesting that the
      morphologies are governed by the kinetical factors together with the
      conventionally accepted thermodynamic ones.

PMID- 29642616
TI  - Scutellarin Mitigates Abeta-Induced Neurotoxicity and Improves Behavior
      Impairments in AD Mice.
AB  - Alzheimer's disease (AD) is pathologically characterized by excessive
      accumulation of amyloid-beta (Abeta) within extracellular spaces of the brain.
      Aggregation of Abeta has been shown to trigger oxidative stress, inflammation,
      and neurotoxicity resulting in cognitive dysfunction. In this study, we use
      models of cerebral Abeta amyloidosis to investigate anti-amyloidogenic effects of
      scutellarin in vitro and in vivo. Our results show that scutellarin, through
      binding to Abeta42, efficiently inhibits oligomerization as well as fibril
      formation and reduces Abeta oligomer-induced neuronal toxicity in cell line SH
      SY5Y. After nine months of treatment in APP/PS1 double-transgenic mice,
      scutellarin significantly improves behavior, reduces soluble and insoluble Abeta
      levels in the brain and plasma, decreases Abeta plaque associated gliosis and
      levels of proinflammatory cytokines TNF-alpha and IL-6, attenuates
      neuroinflammation, displays anti-amyloidogenic effects, and highlights the
      beneficial effects of intervention on development or progression of AD-like
      neuropathology.

PMID- 29642617
TI  - Effects of Lignans from Schisandra chinensis Rattan Stems against Abeta1-42
      Induced Memory Impairment in Rats and Neurotoxicity in Primary Neuronal Cells.
AB  - Oxidative stress, which is caused by Amyloid-beta deposition in brain, plays an
      important role in Alzheimer's disease. In this study, we found that lignans from
      Schisandra chinensis rattan stems (rsSCH-L) could reduce the escape latency and
      the distance travelled by the Abeta1-42 injected rats while the crossing platform
      time was enhanced in the Morris water maze test. Further research demonstrated
      that lignans from rsSCH-L attenuated Abeta1-42-induced neuronal cell injury by
      increasing the content of SOD and GSH-Px and decreasing the levels of LDH, ROS,
      and MDA. Moreover, rsSCH-L also inhibited the apoptosis of primary neuronal
      cells. The mechanisms of the apoptosis were related with the downregulation of
      caspase-3, caspase-8, Bax, and upregulation of Bcl-2. Taken together, the results
      show that rsSCH-L can improve cognitive ability in vivo. Meanwhile rsSCH-L
      exhibit a neuroprotective environment against oxidative stress and apoptosis in
      vitro. Therefore, rsSCH-L may be a potential therapeutic agent for this
      neurodegenerative disease.

PMID- 29642618
TI  - The Role of Extracellular Vesicles in Bone Metastasis.
AB  - Multiple types of cancer have the specific ability to home to the bone
      microenvironment and cause metastatic lesions. Despite being the focus of intense
      investigation, the molecular and cellular mechanisms that regulate the metastasis
      of disseminated tumor cells still remain largely unknown. Bone metastases
      severely impact quality of life since they are associated with pain, fractures,
      and bone marrow aplasia. In this review, we will summarize the recent discoveries
      on the role of extracellular vesicles (EV) in the regulation of bone remodeling
      activity and bone metastasis occurrence. Indeed, it was shown that extracellular
      vesicles, including exosomes and microvesicles, released from tumor cells can
      modify the bone microenvironment, allowing the formation of osteolytic,
      osteosclerotic, and mixed mestastases. In turn, bone-derived EV can stimulate the
      proliferation of tumor cells. The inhibition of EV-mediated crosstalk between
      cancer and bone cells could represent a new therapeutic target for bone
      metastasis.

PMID- 29642619
TI  - Proton Beam Therapy Alone for Intermediate- or High-Risk Prostate Cancer: An
      Institutional Prospective Cohort Study.
AB  - The role of proton beam therapy (PBT) as monotherapy for localized prostate
      cancer (PCa) remains unclear. The purpose of this study was to evaluate the
      efficacy and adverse events of PBT alone for these patients. Between January 2011
      and July 2014, 218 patients with intermediate- and high-risk PCa who declined
      androgen deprivation therapy (ADT) were enrolled to the study and were treated
      with PBT following one of the following protocols: 74 Gray (GyE) with 37
      fractions (fr) (74 GyE/37 fr), 78 GyE/39 fr, and 70 GyE/28 fr. The 5-year
      progression-free survival rate in the intermediate- and high-risk groups was 97%
      and 83%, respectively (p = 0.002). The rate of grade 2 or higher late
      gastrointestinal toxicity was 3.9%, and a significant increased incidence was
      noted in those who received the 78 GyE/39 fr protocol (p < 0.05). Grade 2 or
      higher acute and late genitourinary toxicities were observed in 23.5% and 3.4% of
      patients, respectively. Our results indicated that PBT monotherapy can be a
      beneficial treatment for localized PCa. Furthermore, it can preserve the quality
      of life of these patients. We believe that this study provides crucial hypotheses
      for further study and for establishing new treatment strategies.

PMID- 29642621
TI  - Tailored Synthesis of Core-Shell Mesoporous Silica Particles-Optimization of Dye
      Sorption Properties.
AB  - Monodisperse spherical silica particles, with solid cores and mesoporous shells
      (SCMS), were synthesized at various temperatures using a one-pot method utilizing
      a cationic surfactant template. The temperature of the synthesis was found to
      significantly affect the diameters of both the cores (ca. 170-800 nm) and shells
      (ca. 11-80 nm) of the particles, which can be tailored for specific applications
      that require a high specific surface area of the nanocarriers (mesoporous shells)
      and simultaneously their mechanical robustness for, e.g., facile isolation from
      suspensions (dense cores). The applied method enabled the formation of the
      relatively thick mesoporous shells at conditions below room temperature. Radially
      ordered pores with narrow distributions of their sizes in 3-4 nm range were found
      in the shells. The adsorption ability of the SCMS particles was studied using
      rhodamine 6G as a model dye. Decolorization of the dye solution in the presence
      of the SCMS particles was correlated with their structure and specific surface
      area and reached its maximum for the particles synthesized at 15  degrees C. The
      presented strategy may be applied for the fine-tuning of the structure of SCMS
      particles and the enhancement of their adsorption capabilities.

PMID- 29642615
TI  - YAP/TAZ Activation as a Target for Treating Metastatic Cancer.
AB  - Yes-Associated Protein (YAP) and Transcriptional Co-activator with PDZ-binding
      Motif (TAZ) have both emerged as important drivers of cancer progression and
      metastasis. YAP and TAZ are often upregulated or nuclear localized in aggressive
      human cancers. There is abundant experimental evidence demonstrating that YAP or
      TAZ activation promotes cancer formation, tumor progression, and metastasis. In
      this review we summarize the evidence linking YAP/TAZ activation to metastasis,
      and discuss the roles of YAP and TAZ during each step of the metastatic cascade.
      Collectively, this evidence strongly suggests that inappropriate YAP or TAZ
      activity plays a causal role in cancer, and that targeting aberrant YAP/TAZ
      activation is a promising strategy for the treatment of metastatic disease. To
      this end, we also discuss several potential strategies for inhibiting YAP/TAZ
      activation in cancer and the challenges each strategy poses.

PMID- 29642620
TI  - Rhodobacter sphaeroides Extract LycogenTM Attenuates Testosterone-Induced Benign
      Prostate Hyperplasia in Rats.
AB  - Benign prostate hyperplasia (BPH) is one of the most common urological problems
      in mid-aged to elderly men. Risk factors of BPH include family history, obesity,
      type 2 diabetes, and high oxidative stress. The main medication classes for BPH
      management are alpha blockers and 5alpha-reductase inhibitors. However, these
      conventional medicines cause adverse effects. LycogenTM, extracted from
      Rhodobacter sphaeroides WL-APD911, is an anti-oxidant and anti-inflammatory
      compound. In this study, the effect of LycogenTM was evaluated in rats with
      testosterone-induced benign prostate hyperplasia (BPH). Testosterone injections
      and LycogenTM administration were carried out for 28 days, and body weights were
      recorded twice per week. The testosterone injection successfully induced a
      prostate enlargement. BPH-induced rats treated with different doses of LycogenTM
      exhibited a significantly decreased prostate index (PI). Moreover, the LycogenTM
      administration recovered the histological abnormalities observed in the prostate
      of BPH rats. In conclusion, these findings support a dose-dependent preventing
      effect of LycogenTM on testosterone-induced BPH in rats and suggest that
      LycogenTM may be favorable to the prevention and management of benign prostate
      hyperplasia.

PMID- 29642622
TI  - Colibactin: More Than a New Bacterial Toxin.
AB  - Cyclomodulins are bacterial toxins that interfere with the eukaryotic cell cycle.
      A new cyclomodulin called colibactin, which is synthetized by the pks genomic
      island, was discovered in 2006. Despite many efforts, colibactin has not yet been
      purified, and its structure remains elusive. Interestingly, the pks island is
      found in members of the family Enterobacteriaceae (mainly Escherichia coli and
      Klebsiella pneumoniae) isolated from different origins, including from intestinal
      microbiota, septicaemia, newborn meningitis, and urinary tract infections.
      Colibactin-producing bacteria induce chromosomal instability and DNA damage in
      eukaryotic cells, which leads to senescence of epithelial cells and apoptosis of
      immune cells. The pks island is mainly observed in B2 phylogroup E. coli strains,
      which include extra-intestinal pathogenic E. coli strains, and pksE. coli are
      over-represented in biopsies isolated from colorectal cancer. In addition, pksE.
      coli bacteria increase the number of tumours in diverse colorectal cancer mouse
      models. Thus, colibactin could have a major impact on human health. In the
      present review, we will focus on the biological effects of colibactin, the
      distribution of the pks island, and summarize what is currently known about its
      synthesis and its structure.

PMID- 29642623
TI  - Heavy Metal Pollution Delineation Based on Uncertainty in a Coastal Industrial
      City in the Yangtze River Delta, China.
AB  - Assessing heavy metal pollution and delineating pollution are the bases for
      evaluating pollution and determining a cost-effective remediation plan. Most
      existing studies are based on the spatial distribution of pollutants but ignore
      related uncertainty. In this study, eight heavy-metal concentrations (Cr, Pb, Cd,
      Hg, Zn, Cu, Ni, and Zn) were collected at 1040 sampling sites in a coastal
      industrial city in the Yangtze River Delta, China. The single pollution index
      (PI) and Nemerow integrated pollution index (NIPI) were calculated for every
      surface sample (0-20 cm) to assess the degree of heavy metal pollution. Ordinary
      kriging (OK) was used to map the spatial distribution of heavy metals content and
      NIPI. Then, we delineated composite heavy metal contamination based on the
      uncertainty produced by indicator kriging (IK). The results showed that mean
      values of all PIs and NIPIs were at safe levels. Heavy metals were most
      accumulated in the central portion of the study area. Based on IK, the spatial
      probability of composite heavy metal pollution was computed. The probability of
      composite contamination in the central core urban area was highest. A probability
      of 0.6 was found as the optimum probability threshold to delineate polluted areas
      from unpolluted areas for integrative heavy metal contamination. Results of
      pollution delineation based on uncertainty showed the proportion of false
      negative error areas was 6.34%, while the proportion of false positive error
      areas was 0.86%. The accuracy of the classification was 92.80%. This indicated
      the method we developed is a valuable tool for delineating heavy metal pollution.

PMID- 29642624
TI  - Understanding and Increasing Influenza Vaccination Acceptance: Insights from a
      2016 National Survey of U.S. Adults.
AB  - Background: The percentage of adults in the U.S. getting seasonal influenza
      vaccination has not changed significantly since 2013 and remains far below the
      federal government's 70% target. Objective: This study assessed and identified
      characteristics, experiences, and beliefs associated with influenza vaccination
      using a nationally representative survey of 1005 U.S. adults 19 years old and
      older. Methods: The sample was drawn from the National Opinion Research Center's
      AmeriSpeak Panel, a probability-based panel designed to be representative of the
      U.S. household population. Results: Overall, 42.3% received an influenza
      vaccination in the past 12 months, with rates highest for non-Hispanic Whites and
      Blacks and those 65 years old and older. Hispanic respondents and those under 64
      years old were much less likely to get an influenza vaccination. They were also
      less aware of the recommendation, less informed about influenza and the benefits
      of vaccination, and least confident in the vaccine. Conclusions: Increasing
      influenza vaccination coverage in the U.S. requires a greater focus on 19-64 year
      olds, particularly those 50 to 64, Hispanics and continued focus on those with
      diabetes and asthma. Efforts need to increase awareness of influenza vaccination
      recommendations, foster a sense of being well informed about influenza
      vaccination benefits and the risks associated with non-vaccination, and increase
      confidence that there are meaningful benefits from receiving an influenza
      vaccination.

PMID- 29642625
TI  - Analysis of Sociodemographic, Psychological, and Genetic Factors Contributing to
      Depressive symptoms in Pre-, Peri- and Postmenopausal Women.
AB  - : Depressive symptoms that are faced by women in the pre-, peri-, and
      postmenopausal periods are determined by a wide array of sociodemographic,
      psychological, and biological variables. The aim of our study was to identify
      factors that contribute to depressive problems at this stage of life. The study
      included 815 healthy Polish women aged 45-60 years. The survey part was conducted
      using the Beck Depression Inventory (BDI), the State-Trait Anxiety Inventory
      (STAI), the Neuroticism-Extroversion-Openness Five Factor Inventory (NEO-FFI),
      and a self-developed questionnaire. Genetic analysis was also performed.
      Depressive symptoms were observed in 25.5% of participants. 70% of the women were
      postmenopausal. No statistically significant differences in the severity of
      depressive symptoms were demonstrated with regard to genetic variables (p >
      0.05). Reproductive capacity (p < 0.001), employment (p < 0.001), and being
      married (p < 0.018) were found to reduce the incidence of depressive symptoms.
      The contribution of personality and anxiety as a trait to depressive symptoms
      varied. CONCLUSIONS: The factors predisposing pre-, peri-, and postmenopausal
      women to depressive symptoms include lower education, lack of a life partner,
      unemployment, high anxiety, and neurotic personality. No evidence was found for
      the contribution of genetic factors to depressive symptoms in the examined women.

PMID- 29642626
TI  - Highly Efficient Low-Temperature N-Doped TiO2 Catalysts for Visible Light
      Photocatalytic Applications.
AB  - In this paper, TiO2 prepared with an aqueous sol-gel synthesis by peptization
      process is doped with nitrogen precursor to extend its activity towards the
      visible region. Three N-precursors are used: urea, ethylenediamine and
      triethylamine. Different molar N/Ti ratios are tested and the synthesis is
      adapted for each dopant. For urea- and trimethylamine-doped samples, anatase
      brookite TiO2 nanoparticles of 6-8 nm are formed, with a specific surface area
      between 200 and 275 m2.g-1. In ethylenediamine-doped samples, the formation of
      rutile phase is observed, and TiO2 nanoparticles of 6-8 nm with a specific
      surface area between 185 and 240 m2.g-1 are obtained. X-ray photoelectron
      spectroscopy (XPS) and diffuse reflectance measurements show the incorporation of
      nitrogen in TiO2 materials through Ti-O-N bonds allowing light absorption in the
      visible region. Photocatalytic tests on the remediation of water polluted with p
      nitrophenol show a marked improvement for all doped catalysts under visible
      light. The optimum doping, taking into account cost, activity and ease of
      synthesis, is up-scaled to a volume of 5 L and compared to commercial Degussa P25
      material. This up-scaled sample shows similar properties compared to the lab
      scale sample, i.e., a photoactivity 4 times higher than commercial P25.

PMID- 29642628
TI  - Promoting Water Consumption on a Caribbean Island: An Intervention Using
      Children's Social Networks at Schools.
AB  - Sugar-sweetened beverage (SSB) consumption and the associated childhood obesity
      are major concerns in the Caribbean, creating a need for interventions promoting
      water consumption as a healthy alternative. A social network-based intervention
      (SNI) was tested among Aruban children to increase their water consumption and
      behavioral intention to do so and, consequently, to decrease SSB consumption and
      the associated behavioral intention. In this study, the moderating effects of
      descriptive and injunctive norms were tested. A cluster randomized controlled
      trial was completed in schools (mean age = 11 years +/- SD = 0.98; 54% girls).
      Children were assigned to the intervention group (IG; n = 192) or control group
      (CG; n = 185). IG children were exposed to peer influencers promoting water
      consumption and CG children were not. Regression analyses showed that water
      consumption increased for IG children with a high injunctive norm score (p =
      0.05); however, their intention to consume more water remained unchanged (p =
      0.42). Moreover, IG children showed a decrease in SSB consumption (p = 0.04) and
      an increase in their intention to consume less SSB (p = 0.00). These findings
      indicate that SNIs are a promising instrument for health behavioral changes for
      Aruba and other islands in the Caribbean region.

PMID- 29642627
TI  - A Review of the Interactions between Wheat and Wheat Pathogens: Zymoseptoria
      tritici, Fusarium spp. and Parastagonospora nodorum.
AB  - Zymoseptoria tritici is a hemibiotrophic pathogen which causes Septoria leaf
      blotch in wheat. The pathogenesis of the disease consists of a biotrophic phase
      and a necrotrophic phase. The pathogen infects the host plant by suppressing its
      immune response in the first stage of infection. Hemibiotrophic pathogens of the
      genus Fusarium cause Fusarium head blight, and the necrotrophic
      Parastagonosporanodorum is responsible for Septoria nodorum blotch in wheat. Cell
      wall-degrading enzymes in plants promote infections by necrotrophic and
      hemibiotrophic pathogens, and trichothecenes, secondary fungal metabolites,
      facilitate infections caused by fungi of the genus Fusarium. There are no sources
      of complete resistance to the above pathogens in wheat. Defense mechanisms in
      wheat are controlled by many genes encoding resistance traits. In the wheat
      genome, the characteristic features of loci responsible for resistance to
      pathogenic infections indicate that at least several dozen genes encode
      resistance to pathogens. The molecular interactions between wheat and Z. tritici,
      P. nodorum and Fusarium spp. pathogens have been insufficiently investigated.
      Most studies focus on the mechanisms by which the hemibiotrophic Z. tritici
      suppresses immune responses in plants and the role of mycotoxins and effector
      proteins in infections caused by P. nodorum and Fusarium spp. fungi.
      Trichothecene glycosylation and effector proteins, which are involved in defense
      responses in wheat, have been described at the molecular level. Recent advances
      in molecular biology have produced interesting findings which should be further
      elucidated in studies of molecular interactions between wheat and fungal
      pathogens. The Clustered Regularly-Interspaced Short Palindromic Repeats/ CRISPR
      associated (CRISPR/Cas) system can be used to introduce targeted mutations into
      the wheat genome and confer resistance to selected fungal diseases. Host-induced
      gene silencing and spray-induced gene silencing are also useful tools for
      analyzing wheat-pathogens interactions which can be used to develop new
      strategies for controlling fungal diseases.

PMID- 29642629
TI  - 17beta-Hydroxysteroid Dehydrogenase Type 2 Expression Is Induced by Androgen
      Signaling in Endometrial Cancer.
AB  - Endometrial cancer is one of the most common female pelvic cancers and has been
      considered an androgen-related malignancy. Several studies have demonstrated the
      anti-cell proliferative effect of androgen on endometrial cancer cells; however,
      the mechanisms of the anti-cancer effect of androgen remain largely unclear.
      17beta-hydroxysteroid dehydrogenase type 2 (17beta-HSD2), which catalyzes the
      conversion of E2 to E1, is known to be upregulated by androgen treatment in
      breast cancer cells. In this study, we therefore focused on the role of androgen
      on estrogen dependence in endometrial cancer. Dihydrotestosterone (DHT) was found
      to induce 17beta-HSD2 mRNA and protein expression in HEC-1B endometrial cancer
      cells. DHT could also inhibit cell proliferation of HEC-1B when induced by
      estradiol treatment. In 19 endometrioid endometrial adenocarcinoma (EEA) tissues,
      intratumoral DHT concentration was measured by liquid chromatography/electrospray
      tandem mass spectrometry and was found to be significantly correlated with 17beta
      HSD2 immunohistochemical status. We further examined the correlations between
      17beta-HSD2 immunoreactivity and clinicopathological parameters in 53 EEA
      tissues. 17beta-HSD2 status was inversely associated with the histological grade,
      clinical stage, and cell proliferation marker Ki-67, and positively correlated
      with progesterone receptor expression. 17beta-HSD2 status tended to be positively
      associated with androgen receptor status. In 53 EEA cases, the 17beta-HSD2
      positive group tended to have better prognosis than that for the negative group
      with respect to progression-free survival and endometrial cancer-specific
      survival. These findings suggest that androgen suppresses the estrogen dependence
      of endometrial cancer through the induction of 17beta-HSD2 in endometrial cancer.

PMID- 29642630
TI  - Aging and Intermittent Fasting Impact on Transcriptional Regulation and
      Physiological Responses of Adult Drosophila Neuronal and Muscle Tissues.
AB  - The progressive decline of the nervous system, including protein aggregate
      formation, reflects the subtle dysregulation of multiple functional pathways. Our
      previous work has shown intermittent fasting (IF) enhances longevity, maintains
      adult behaviors and reduces aggregates, in part, by promoting autophagic function
      in the aging Drosophila brain. To clarify the impact that IF-treatment has upon
      aging, we used high throughput RNA-sequencing technology to examine the changing
      transcriptome in adult Drosophila tissues. Principle component analysis (PCA) and
      other analyses showed ~1200 age-related transcriptional differences in head and
      muscle tissues, with few genes having matching expression patterns. Pathway
      components showing age-dependent expression differences were involved with stress
      response, metabolic, neural and chromatin remodeling functions. Middle-aged
      tissues also showed a significant increase in transcriptional drift-variance
      (TD), which in the CNS included multiple proteolytic pathway components. Overall,
      IF-treatment had a demonstrably positive impact on aged transcriptomes, partly
      ameliorating both fold and variance changes. Consistent with these findings, aged
      IF-treated flies displayed more youthful metabolic, behavioral and basal
      proteolytic profiles that closely correlated with transcriptional alterations to
      key components. These results indicate that even modest dietary changes can have
      therapeutic consequences, slowing the progressive decline of multiple cellular
      systems, including proteostasis in the aging nervous system.

PMID- 29642633
TI  - Structural Requirements of Alkylglyceryl-l-Ascorbic Acid Derivatives for
      Melanogenesis Inhibitory Activity.
AB  - l-Ascorbic acid has multifunctional benefits on skin aesthetics, including
      inhibition of melanin production, and is widely used in cosmetics. It, however,
      has low stability and poor skin penetration. We hypothesize that alkylglyceryl-l
      ascorbic acid derivatives, highly stable vitamin C-alkylglycerol conjugates,
      would have similar anti-melanogenic activity with better stability and
      penetration. We test 28 alkylglyceryl-l-ascorbic acid derivatives (1-28) on
      theophylline-stimulated B16 melanoma 4A5 cells to determine if they inhibit
      melanogenesis and establish any structure-function relationships. Although not
      the most potent inhibitors, 3-O-(2,3-dihydroxypropyl)-2-O-hexyl-l-ascorbic acid
      (6, IC50 = 81.4 uM) and 2-O-(2,3-dihydroxypropyl)-3-O-hexyl-l-ascorbic acid (20,
      IC50 = 117 uM) are deemed the best candidate derivatives based on their
      inhibitory activities and low toxicities. These derivatives are also found to be
      more stable than l-ascorbic acid and to have favorable characteristics for skin
      penetration. The following structural requirements for inhibitory activity of
      alkylglyceryl-l-ascorbic acid derivatives are also determined: (i) alkylation of
      glyceryl-l-ascorbic acid is essential for inhibitory activity; (ii) the 3-O-alkyl
      derivatives (2-14) exhibit stronger inhibitory activity than the corresponding 2
      O-alkyl-derivatives (16-28); and (iii) derivatives with longer alkyl chains have
      stronger inhibitory activities. Mechanistically, our studies suggest that l
      ascorbic acid derivatives exert their effects by suppressing the mRNA expression
      of tyrosinase and tyrosine-related protein-1.

PMID- 29642632
TI  - Atomic Force Microscopy for Protein Detection and Their Physicoshemical
      Characterization.
AB  - This review is focused on the atomic force microscopy (AFM) capabilities to study
      the properties of protein biomolecules and to detect the proteins in solution.
      The possibilities of application of a wide range of measuring techniques and
      modes for visualization of proteins, determination of their stoichiometric
      characteristics and physicochemical properties, are analyzed. Particular
      attention is paid to the use of AFM as a molecular detector for detection of
      proteins in solutions at low concentrations, and also for determination of
      functional properties of single biomolecules, including the activity of
      individual molecules of enzymes. Prospects for the development of AFM in
      combination with other methods for studying biomacromolecules are discussed.

PMID- 29642634
TI  - Bio-Based Cellulose Acetate Films Reinforced with Lignin and Glycerol.
AB  - Two sets of four cellulose acetate (degree of substitution = 2.2) were
      incorporated with lignin extracted from the macauba endocarp, before and after
      being chemically modified to sodium carboxymethyl-lignin and aluminum
      carboxymethyl-lignin, respectively. The eight membranes were prepared by the
      casting method after dissolution in acetone and embedded with lignins (0.1% w/w),
      one without modification (CAc-Lig) and two chemically modified (CAc-CMLNa) and
      (CAc-CMLAl), compared to membranes of pure acetate (CAc). In group II, in the
      four membranes prepared, glycerol was added (10% w/w) as a plasticizer. The
      membranes were characterized by a number of techniques: thermal (differential
      scanning calorimetry (DSC) and thermogravimetric analysis (TGA)), morphological
      (scanning electron microscope (SEM) and atomic force microscopy (AFM)),
      structural (X-ray powder diffraction (XRD)), hydrophobic (contact angle and water
      vapor permeability), and thermomechanical (dynamic thermal mechanical analysis
      and tensile tests). The results show that despite some incompatibility with the
      cellulose acetate, the incorporation of the lignin in a concentration of 0.1% w/w
      acts as a reinforcement in the membrane, greatly increasing the tension rupture
      of the material. The presence of glycerol in a concentration of 10% w/w also acts
      as a reinforcement in all membranes, in addition to increasing the tension
      rupture. In this study, glycerol and acetate both increased the compatibility of
      the membranes.

PMID- 29642636
TI  - Gliadin Peptide Facilitates FITC Dextran Transport across the Non Everted Gut Sac
      of Rat Small Intestine.
AB  - Superoxide dismutase (SOD) is an antioxidant protein. When administered orally,
      it has low bioavailability due to its low permeation. In a previous study we
      fused gliadin peptide P51 (LGQQQPFPPQQPYPQPQPF) and gliadin peptide P61
      (QQPYPQPQPF) with SOD Citrus limon (SOD_Cl), namely GliSOD_P51 and GliSOD_P61 to
      increase permeation of SOD_Cl through intestine. In this work, the permeation of
      fluorescein isothiocyanate (FITC)-Dextran 10 kDa, FD10 and 40 kDa, FD40 as
      paracellular transport markers across excised rat intestinal wall was
      investigated with the presence of GliSOD_P51 and GliSOD_P61. A permeability study
      was performed using non-everted rat intestine by incubating FD10 or FD40 with
      SOD_Cl, and GliSOD_P61. The presence of SOD_Cl, GliSOD_P51 or GliSOD_P61 inside
      intestine (apical) and outside intestine (basolateral) was analyzed by protein
      electrophoresis. The concentration of FD that penetrated to the basolateral
      solution was analyzed by spectrofluorometry. Sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) analysis revealed the presence of
      GliSOD_P51 and GliSOD_P61 but not SOD_Cl in basolateral compartment. The
      percentage of FD10 but not FD40 and SOD_Cl that penetrated to the basolateral
      solution significantly increased with the presence of gliadin in GliSOD_P51 and
      GliSOD_P61. GliSOD_P51 and GliSOD_P61 are able to penetrate the rat intestinal
      epithelial membrane and the gliadin peptides facilitate FD10 to penetrate the
      epithelial.

PMID- 29642635
TI  - CD147 Promotes CXCL1 Expression and Modulates Liver Fibrogenesis.
AB  - Activated hepatic stellate cells (HSCs) release pro-inflammatory and pro
      fibrogenic factors. CXC chemokine-ligand-1 (CXCL1) is expressed on HSCs. We
      previously found that the CD147 is overexpressed in activated HSCs. In this
      study, we showed an important role of CD147 in promoting liver fibrosis by
      activating HSCs and upregulating expression of chemokines. Specifically, we found
      that CD147 specific deletion in HSCs mice alleviated CCl4-induced liver fibrosis
      and inhibited HSCs activation. Overexpression of CD147 upregulated the secretion
      of CXCL1. Meanwhile, CXCL1 promoted HSCs activation through autocrine. Treating
      with PI3K/AKT inhibitor could effectively suppress CD147-induced CXCL1
      expression. Taken together, these findings suggest that CD147 regulates CXCL1
      release in HSCs by PI3K/AKT signaling. Inhibition of CD147 attenuates CCl4
      induced liver fibrosis and inflammation. Therefore, administration of targeting
      CD147 could be a promising therapeutic strategy in liver fibrosis.

PMID- 29642631
TI  - Prospects of Understanding the Molecular Biology of Disease Resistance in Rice.
AB  - Rice is one of the important crops grown worldwide and is considered as an
      important crop for global food security. Rice is being affected by various
      fungal, bacterial and viral diseases resulting in huge yield losses every year.
      Deployment of resistance genes in various crops is one of the important methods
      of disease management. However, identification, cloning and characterization of
      disease resistance genes is a very tedious effort. To increase the life span of
      resistant cultivars, it is important to understand the molecular basis of plant
      host-pathogen interaction. With the advancement in rice genetics and genomics,
      several rice varieties resistant to fungal, bacterial and viral pathogens have
      been developed. However, resistance response of these varieties break down very
      frequently because of the emergence of more virulent races of the pathogen in
      nature. To increase the durability of resistance genes under field conditions,
      understanding the mechanismof resistance response and its molecular basis should
      be well understood. Some emerging concepts like interspecies transfer of pattern
      recognition receptors (PRRs) and transgenerational plant immunitycan be employed
      to develop sustainable broad spectrum resistant varieties of rice.

PMID- 29642637
TI  - Coherent and Noncoherent Joint Processing of Sonar for Detection of Small Targets
      in Shallow Water.
AB  - A coherent-noncoherent joint processing framework is proposed for active sonar to
      combine diversity gain and beamforming gain for detection of a small target in
      shallow water environments. Sonar utilizes widely-spaced arrays to sense
      environments and illuminate a target of interest from multiple angles. Meanwhile,
      it exploits spatial diversity for time-reversal focusing to suppress
      reverberation, mainly strong bottom reverberation. For enhancement of robustness
      of time-reversal focusing, an adaptive iterative strategy is utilized in the
      processing framework. A probing signal is firstly transmitted and echoes of a
      likely target are utilized as steering vectors for the second transmission. With
      spatial diversity, target bearing and range are estimated using a broadband
      signal model. Numerical simulations show that the novel sonar outperforms the
      traditional phased-array sonar due to benefits of spatial diversity. The
      effectiveness of the proposed framework has been validated by localization of a
      small target in at-lake experiments.

PMID- 29642638
TI  - Analysis of a Smartphone-Based Architecture with Multiple Mobility Sensors for
      Fall Detection with Supervised Learning.
AB  - This paper describes a wearable Fall Detection System (FDS) based on a body-area
      network consisting of four nodes provided with inertial sensors and Bluetooth
      wireless interfaces. The signals captured by the nodes are sent to a smartphone
      which simultaneously acts as another sensing point. In contrast to many FDSs
      proposed by the literature (which only consider a single sensor), the
      multisensory nature of the prototype is utilized to investigate the impact of the
      number and the positions of the sensors on the effectiveness of the production of
      the fall detection decision. In particular, the study assesses the capability of
      four popular machine learning algorithms to discriminate the dynamics of the
      Activities of Daily Living (ADLs) and falls generated by a set of experimental
      subjects, when the combined use of the sensors located on different parts of the
      body is considered. Prior to this, the election of the statistics that optimize
      the characterization of the acceleration signals and the efficacy of the FDS is
      also investigated. As another important methodological novelty in this field, the
      statistical significance of all the results (an aspect which is usually neglected
      by other works) is validated by an analysis of variance (ANOVA).

PMID- 29642639
TI  - Influence of Waveform Characteristics on LiDAR Ranging Accuracy and Precision.
AB  - Time of flight (TOF) based light detection and ranging (LiDAR) is a technology
      for calculating distance between start/stop signals of time of flight. In lab
      built LiDAR, two ranging systems for measuring flying time between start/stop
      signals include time-to-digital converter (TDC) that counts time between trigger
      signals and analog-to-digital converter (ADC) that processes the sampled
      start/stop pulses waveform for time estimation. We study the influence of
      waveform characteristics on range accuracy and precision of two kinds of ranging
      system. Comparing waveform based ranging (WR) with analog discrete return system
      based ranging (AR), a peak detection method (WR-PK) shows the best ranging
      performance because of less execution time, high ranging accuracy, and stable
      precision. Based on a novel statistic mathematical method maximal information
      coefficient (MIC), WR-PK precision has a high linear relationship with the
      received pulse width standard deviation. Thus keeping the received pulse width of
      measuring a constant distance as stable as possible can improve ranging
      precision.

PMID- 29642640
TI  - Predicting Key Agronomic Soil Properties with UV-Vis Fluorescence Measurements
      Combined with Vis-NIR-SWIR Reflectance Spectroscopy: A Farm-Scale Study in a
      Mediterranean Viticultural Agroecosystem.
AB  - For adequate crop and soil management, rapid and accurate techniques for
      monitoring soil properties are particularly important when a farmer starts up his
      activities and needs a diagnosis of his cultivated fields. This study aimed to
      evaluate the potential of fluorescence measured directly on 146 whole soil solid
      samples, for predicting key soil properties at the scale of a 6 ha Mediterranean
      wine estate with contrasting soils. UV-Vis fluorescence measurements were carried
      out in conjunction with reflectance measurements in the Vis-NIR-SWIR range.
      Combining PLSR predictions from Vis-NIR-SWIR reflectance spectra and from a set
      of fluorescence signals enabled us to improve the power of prediction of a number
      of key agronomic soil properties including SOC, Ntot, CaCO3, iron, fine particle
      sizes (clay, fine silt, fine sand), CEC, pH and exchangeable Ca2+ with cross
      validation RPD >= 2 and R2 >= 0.75, while exchangeable K+, Na+, Mg2+, coarse silt
      and coarse sand contents were fairly predicted (1.42 <= RPD < 2 and 0.54 <= R2 <
      0.75). Predictions of SOC, Ntot, CaCO3, iron contents, and pH were still good
      (RPD >= 1.8, R2 >= 0.68) when using a single fluorescence signal or index such as
      SFR_R or FERARI, highlighting the unexpected importance of red excitations and
      indices derived from plant studies. The predictive ability of single fluorescence
      indices or original signals was very significant for topsoil: this is very
      important for a farmer who wishes to update information on soil nutrient for the
      purpose of fertility diagnosis and particularly nitrogen fertilization. These
      results open encouraging perspectives for using miniaturized fluorescence devices
      enabling red excitation coupled with red or far-red fluorescence emissions
      directly in the field.

PMID- 29642641
TI  - Signals of Systemic Immunity in Plants: Progress and Open Questions.
AB  - Systemic acquired resistance (SAR) is a defence mechanism that induces protection
      against a wide range of pathogens in distant, pathogen-free parts of plants after
      a primary inoculation. Multiple mobile compounds were identified as putative SAR
      signals or important factors for influencing movement of SAR signalling elements
      in Arabidopsis and tobacco. These include compounds with very different chemical
      structures like lipid transfer protein DIR1 (DEFECTIVE IN INDUCED RESISTANCE1),
      methyl salicylate (MeSA), dehydroabietinal (DA), azelaic acid (AzA), glycerol-3
      phosphate dependent factor (G3P) and the lysine catabolite pipecolic acid (Pip).
      Genetic studies with different SAR-deficient mutants and silenced lines support
      the idea that some of these compounds (MeSA, DIR1 and G3P) are activated only
      when SAR is induced in darkness. In addition, although AzA doubled in phloem
      exudate of tobacco mosaic virus (TMV) infected tobacco leaves, external AzA
      treatment could not induce resistance neither to viral nor bacterial pathogens,
      independent of light conditions. Besides light intensity and timing of light
      exposition after primary inoculation, spectral distribution of light could also
      influence the SAR induction capacity. Recent data indicated that TMV and CMV
      (cucumber mosaic virus) infection in tobacco, like bacteria in Arabidopsis,
      caused massive accumulation of Pip. Treatment of tobacco leaves with Pip in the
      light, caused a drastic and significant local and systemic decrease in lesion
      size of TMV infection. Moreover, two very recent papers, added in proof,
      demonstrated the role of FMO1 (FLAVIN-DEPENDENT-MONOOXYGENASE1) in conversion of
      Pip to N-hydroxypipecolic acid (NHP). NHP systemically accumulates after
      microbial attack and acts as a potent inducer of plant immunity to bacterial and
      oomycete pathogens in Arabidopsis. These results argue for the pivotal role of
      Pip and NHP as an important signal compound of SAR response in different plants
      against different pathogens.

PMID- 29642642
TI  - Improvement of Strength-Toughness-Hardness Balance in Large Cross-Section 718H
      Pre-Hardened Mold Steel.
AB  - The strength-toughness combination and hardness uniformity in large cross-section
      718H pre-hardened mold steel from a 20 ton ingot were investigated with three
      different heat treatments for industrial applications. The different
      microstructures, including tempered martensite, lower bainite, and retained
      austenite, were obtained at equivalent hardness. The microstructures were
      characterized by using metallographic observations, scanning electron microscopy
      (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), and
      electron back-scattered diffraction (EBSD). The mechanical properties were
      compared by tensile, Charpy U-notch impact and hardness uniformity tests at room
      temperature. The results showed that the test steels after normalizing-quenching
      tempering (N-QT) possessed the best strength-toughness combination and hardness
      uniformity compared with the conventional quenched-tempered (QT) steel. In
      addition, the test steel after austempering-tempering (A-T) demonstrated the
      worse hardness uniformity and lower yield strength while possessing relatively
      higher elongation (17%) compared with the samples after N-QT (14.5%) treatments.
      The better ductility of A-T steel mainly depended on the amount and morphology of
      retained austenite and thermal/deformation-induced twined martensite. This work
      elucidates the mechanisms of microstructure evolution during heat treatments and
      will highly improve the strength-toughness-hardness trade-off in large cross
      section steels.

PMID- 29642645
TI  - A Novel Strategy of Ambiguity Correction for the Improved Faraday Rotation
      Estimator in Linearly Full-Polarimetric SAR Data.
AB  - Spaceborne synthetic aperture radar (SAR) missions operating at low frequencies,
      such as L-band or P-band, are significantly influenced by the ionosphere. As one
      of the serious ionosphere effects, Faraday rotation (FR) is a remarkable
      distortion source for the polarimetric SAR (PolSAR) application. Various
      published FR estimators along with an improved one have been introduced to solve
      this issue, all of which are implemented by processing a set of PolSAR real data.
      The improved estimator exhibits optimal robustness based on performance analysis,
      especially in term of the system noise. However, all published estimators,
      including the improved estimator, suffer from a potential FR angle (FRA)
      ambiguity. A novel strategy of the ambiguity correction for those FR estimators
      is proposed and shown as a flow process, which is divided into pixel-level and
      image-level correction. The former is not yet recognized and thus is considered
      in particular. Finally, the validation experiments show a prominent performance
      of the proposed strategy.

PMID- 29642644
TI  - Wnt Signaling in Thyroid Homeostasis and Carcinogenesis.
AB  - The Wnt pathway is essential for stem cell maintenance, but little is known about
      its role in thyroid hormone signaling and thyroid stem cell survival and
      maintenance. In addition, the role of Wnt signaling in thyroid cancer progenitor
      cells is also unclear. Here, we present emerging evidence for the role of Wnt
      signaling in somatic thyroid stem cell and thyroid cancer stem cell function. An
      improved understanding of the role of Wnt signaling in thyroid physiology and
      carcinogenesis is essential for improving both thyroid disease diagnostics and
      therapeutics.

PMID- 29642646
TI  - A Socio-Technical Exploration for Reducing & Mitigating the Risk of Retained
      Foreign Objects.
AB  - A Retained Foreign Object (RFO) is a fairly infrequent but serious adverse event.
      An accurate rate of RFOs is difficult to establish due to underreporting but it
      has been estimated that incidences range between 1/1000 and 1/19,000 procedures.
      The cost of a RFO incident may be substantial and three-fold: (i) the cost to the
      patient of physical and/or psychological harm; (ii) the reputational cost to an
      institution and/or healthcare provider; and (iii) the financial cost to the
      taxpayer in the event of a legal claim. This Health Research Board-funded project
      aims to analyse and understand the problem of RFOs in surgical and maternity
      settings in Ireland and develop hospital-specific foreign object management
      processes and implementation roadmaps. This project will deploy an integrated
      evidence-based assessment methodology for social-technical modelling (Supply,
      Context, Organising, Process & Effects/ SCOPE Analysis Cube) and bow tie
      methodologies that focuses on managing the risks in effectively implementing and
      sustaining change. It comprises a multi-phase research approach that involves
      active and ongoing collaboration with clinical and other healthcare staff through
      each phase of the research. The specific objective of this paper is to present
      the methodological approach and outline the potential to produce generalisable
      results which could be applied to other health-related issues.

PMID- 29642647
TI  - ERBB1- and ERBB2-Positive Medullary Thyroid Carcinoma: A Case Report.
AB  - Medullary thyroid carcinomas (MTCs) are rare thyroid tumors occurring in both
      sporadic and hereditary forms, whose pathogenesis is related to RET proto
      oncogene alterations. MTCs originate from parafollicular cells, which produce
      calcitonin that represents the biochemical activity of MTC. Total thyroidectomy
      is the main treatment for MTC and often cures patients with confined diseases. In
      the presence of metastasis, the therapeutic approach depends on the rate of
      disease progression. We report a case of a 54-year-old female with a single,
      incidentally discovered, thyroid nodule of 1 cm, classified as suspicious MTC
      after a stimulation test with intravenous (iv) calcium. After surgery, we
      examined the nodule using immunohistochemistry, immunofluorescence, and electron
      microscopy. In addition to calcitonin, we found that it expressed intracellular
      positivity for the tyrosine kinase RTK receptors ERBB1 and ERBB2. Consistently
      with MTC features, the ultrastructural examination of the tumor displayed
      heterogeneous spindle-shaped cells containing two groups of secretory granules.
      Because of the significant correlation found between high ERBB1/ERBB2 levels in
      MTCs and extrathyroidal growth, the detection of ERBB1 and ERBB2 expression
      suggests that the two oncoproteins may be involved in the tumor proliferative
      responses and/or in the differentiation of parafollicular C-cells. The
      biological, prognostic, and therapeutic significance of these patterns would
      merit further investigations.

PMID- 29642648
TI  - PL-VIO: Tightly-Coupled Monocular Visual-Inertial Odometry Using Point and Line
      Features.
AB  - To address the problem of estimating camera trajectory and to build a structural
      three-dimensional (3D) map based on inertial measurements and visual
      observations, this paper proposes point-line visual-inertial odometry (PL-VIO), a
      tightly-coupled monocular visual-inertial odometry system exploiting both point
      and line features. Compared with point features, lines provide significantly more
      geometrical structure information on the environment. To obtain both computation
      simplicity and representational compactness of a 3D spatial line, Plucker
      coordinates and orthonormal representation for the line are employed. To tightly
      and efficiently fuse the information from inertial measurement units (IMUs) and
      visual sensors, we optimize the states by minimizing a cost function which
      combines the pre-integrated IMU error term together with the point and line re
      projection error terms in a sliding window optimization framework. The
      experiments evaluated on public datasets demonstrate that the PL-VIO method that
      combines point and line features outperforms several state-of-the-art VIO systems
      which use point features only.

PMID- 29642643
TI  - The Many Roles of Ubiquitin in NF-kappaB Signaling.
AB  - The nuclear factor kappaB (NF-kappaB) signaling pathway ubiquitously controls
      cell growth and survival in basic conditions as well as rapid resetting of
      cellular functions following environment changes or pathogenic insults. Moreover,
      its deregulation is frequently observed during cell transformation, chronic
      inflammation or autoimmunity. Understanding how it is properly regulated
      therefore is a prerequisite to managing these adverse situations. Over the last
      years evidence has accumulated showing that ubiquitination is a key process in NF
      kappaB activation and its resolution. Here, we examine the various functions of
      ubiquitin in NF-kappaB signaling and more specifically, how it controls signal
      transduction at the molecular level and impacts in vivo on NF-kappaB regulated
      cellular processes.

PMID- 29642649
TI  - Portrait of Matrix Gene Expression in Candida glabrata Biofilms with Stress
      Induced by Different Drugs.
AB  - (1) Background: Candida glabrata is one of the most significant Candida species
      associated with severe cases of candidiasis. Biofilm formation is an important
      feature, closely associated with antifungal resistance, involving alterations of
      gene expression or mutations, which can result in the failure of antifungal
      treatments. Hence, the main goal of this work was to evaluate the role of a set
      of genes, associated with matrix production, in the resistance of C. glabrata
      biofilms to antifungal drugs. (2) Methods: the determination of the expression of
      BGL2, XOG1, FKS1, FKS2, GAS2, KNH1, UGP1, and MNN2 genes in 48-h biofilm's cells
      of three C. glabrata strains was performed through quantitative real-time PCR (RT
      qPCR), after contact with Fluconazole (Flu), Amphotericin B (AmB), Caspofungin
      (Csf), or Micafungin (Mcf). (3) Results: Mcf induced a general overexpression of
      the selected genes. It was verified that the genes related to the production of
      beta-1,3-glucans (BGL2, XOG1, GAS2) had the highest expressions. (4) Conclusion:
      though beta-1,6-glucans and mannans are an essential part of the cell and biofilm
      matrix, C. glabrata biofilm cells seem to contribute more to the replacement of
      beta-1,3-glucans. Thus, these biopolymers seem to have a greater impact on the
      biofilm matrix composition and, consequently, a role in the biofilm resistance to
      antifungal drugs.

PMID- 29642650
TI  - A Novel Colorimetric Fluorescent Probe for SO2 and Its Application in Living
      Cells Imaging.
AB  - A novel chromenylium-based fluorescent probe was exploited for sulphur dioxide
      (SO2) detecting. The probe displayed a remarkable fluorescence turn-on response
      towards SO2 based on the nucleophilic addition reaction to the carbon-carbon
      double bond with 105 nm Stock shift. The probe was successfully applied for the
      quantification of SO2.The linear detection range was from 0-160 MUM with the
      detection limit as low as 99.27 nM. It also exhibited high selectivity for SO2
      than other reactive species and amino acids. Furthermore, cell staining
      experiments indicated that the probe was cell membrane permeable and could be
      used for high-performance imaging of SO2 in living cells. The superior properties
      of the probe made it highly promising for use in chemical and biological
      applications.

PMID- 29642652
TI  - Waterborne Superhydrophobic and Superoleophobic Coatings for the Protection of
      Marble and Sandstone.
AB  - Silica nanoparticles were dispersed in an aqueous emulsion of alkoxy silanes and
      organic fluoropolymer. The dispersion was sprayed onto white marble and
      sandstone. The deposited composite coatings exhibited (i) superhydrophobicity and
      superoleophobicity, as evidenced by the high (>150 degrees ) static contact
      angles of water and oil drops as well as (ii) water and oil repellency according
      to the low (<7 degrees ) corresponding tilt contact angles. Apart from marble and
      sandstone, the coatings with extreme wetting properties were deposited onto
      concrete, silk, and paper, thus demonstrating the versatility of the method. The
      siloxane/fluoropolymer product was characterized using Fourier Transform Infrared
      Spectroscopy (FT-IR), Raman spectroscopy and Scanning Electron Microscopy
      equipped with an Energy Dispersive X-ray Spectrometer (SEM-EDX). Moreover, SEM
      and FT-IR were used to reveal the surface structures of the composite coatings
      and their transition from superhydrophobicity to superhydrophilicity which
      occurred after severe thermal treatment. The composite coatings slightly reduced
      the breathability of marble and sandstone and had practically no optical effect
      on the colour of the two stones. Moreover, the coatings offered good protection
      against water penetration by capillarity.

PMID- 29642651
TI  - The Multifunctional Role of Chitosan in Horticultural Crops; A Review.
AB  - Chitosan is a naturally occurring compound and is commercially produced from
      seafood shells. It has been utilized in the induction of the defense system in
      both pre and post-harvest fruits and vegetables against fungi, bacteria, viruses,
      and other abiotic stresses. In addition to that, chitosan effectively improves
      the physiological properties of plants and also enhances the shelf life of post
      harvest produces. Moreover, chitosan treatment regulates several genes in plants,
      particularly the activation of plant defense signaling pathways. That includes
      the elicitation of phytoalexins and pathogenesis-related (PR) protein. Besides
      that, chitosan has been employed in soil as a plant nutrient and has shown great
      efficacy in combination with other industrial fertilizers without affecting the
      soil's beneficial microbes. Furthermore, it is helpful in reducing the fertilizer
      losses due to its coating ability, which is important in keeping the
      environmental pollution under check. Based on exhibiting such excellent
      properties, there is a striking interest in using chitosan biopolymers in
      agriculture systems. Therefore, our current review has been centered upon the
      multiple roles of chitosan in horticultural crops that could be useful in future
      crop improvement programs.

PMID- 29642653
TI  - Road dust and its effect on human health: a literature review.
AB  - The purpose of this study was to determine the effects of road dust on human
      health. A PubMed search was used to extract references that included the words
      "road dust" and "health" or "fugitive dust" and "health" in the title or
      abstract. A total of 46 references were extracted and selected for review after
      the primary screening of 949 articles. The respiratory system was found to be the
      most affected system in the human body. Lead, platinum-group elements (platinum,
      rhodium, and bohrium), aluminum, zinc, vanadium, and polycyclic aromatic
      hydrocarbons were the components of road dust that were most frequently
      referenced in the articles reviewed. Road dust was found to have harmful effects
      on the human body, especially on the respiratory system. To determine the complex
      mechanism of action of various components of road dust on the human body and the
      results thereof, the authors recommend a further meta-analysis and extensive risk
      assessment research into the health impacts of dust exposure.

PMID- 29642654
TI  - Income-related inequality in completed suicide across the provinces of Iran.
AB  - OBJECTIVES: The aim of this study was to measure income-related inequality in
      completed suicide across the provinces of Iran. METHODS: This ecological study
      was performed using data from the Urban and Rural Household Income and
      Expenditure Survey-2010 conducted by the Iranian Center of Statistics, along with
      data on completed suicide from the Iranian Legal Medicine Organization in 2012.
      We calculated the Gini coefficient of per capita income and the completed suicide
      rate, as well as the concentration index for per capita income inequality in
      completed suicide, across the provinces of Iran. RESULTS: The Gini coefficients
      of per capita income and the completed suicide rate in the provinces of Iran were
      0.10 (95% confidence interval [CI], 0.06 to 0.13) and 0.34 (95% CI, 0.21 to
      0.46), respectively. We found a trivial decreasing trend in the completed suicide
      incidence rate according to income quintile. The poorest-to-richest ratio in the
      completed suicide rate was 2.01 (95% CI, 1.26 to 3.22). The concentration index
      of completed suicide in the provinces of Iran was -0.12 (95% CI, -0.30 to 0.06).
      CONCLUSIONS: This study found that lower income might be considered as a risk
      factor for completed suicide. Nonetheless, further individual studies
      incorporating multivariable analysis and repeated cross-sectional data would
      allow a more fine-grained analysis of this phenomenon.

PMID- 29642655
TI  - Factors related to cancer screening behaviors.
AB  - OBJECTIVES: This study aimed to investigate the factors related to cancer
      screening behaviors (CSB). METHODS: The 2014 Korean Community Health Survey used
      for analysis. The dependent variable was CSB, and the independent variables were
      demographic, health behavioral, and regional factor. Propensity score matching
      (PSM) used to control health behavior and regional factors, which were
      influencing CSB. For statistical analysis, chi-square test and logistic
      regression analysis used. RESULTS: Logistic regression analysis after PSM showed
      that gender, age, marital status, educational level, monthly household income,
      employment type, alcohol drinking, smoking, body mass index group, chronic
      disease, and subjective health status influenced the CSB, there were statistical
      differences. CONCLUSIONS: To improve cancer screening (CS), it is necessary to
      educate individuals on the need for CS and to carry out a personalized CS program
      based on an individual's demographic status and health behavior.

PMID- 29642656
TI  - Socioeconomic disparities and difficulties to access to healthcare services among
      Canadian children with neurodevelopmental disorders and disabilities.
AB  - OBJECTIVES: The aims of this study were to identify the associations of levels of
      severity of neurodevelopmental disorders and disabilities (NDD/D) in children
      with their household socioeconomic status (SES) and their frequency of visits to
      a healthcare provider, and to examine how the severity of disability varied with
      these determinants among NDD/D subgroups, in order to inform possible social
      policy changes and to improve access to the healthcare system. METHODS: Data from
      the 2006 Participation and Activity Limitation Survey on children aged 5-14
      years, collected by Statistics Canada, were analyzed (n=7,072 and weighted
      n=340,340). Children with NDD/D constituted those with impairments in motor,
      speech, neurosensory, and psychological functioning, as well as those who had
      issues with learning/cognition and social interactions. The weighted sample size
      for this group was n=111,630 (total sample size for children with limitations:
      n=174,810). We used logistic regression to assess the associations of household
      SES and frequency of visits to a healthcare provider with disability level. We
      included NDD/D subgroups as interaction terms in the model. Multiple
      correspondence analysis (MCA) was conducted to develop a profile of disability
      level. RESULTS: After-tax low income, family assistance, out-of-pocket expenses,
      needing but not receiving health services from a social worker, condition of the
      dwelling, and residential location were associated with the severity of NDD/D.
      Using MCA, 2 disability profiles could be identified based on access to
      healthcare, household income status, and condition of the dwelling. CONCLUSIONS:
      More social interventions are needed to reduce difficulties in accessing
      healthcare and to diminish the socially determined health inequalities faced by
      children with NDD/D.

PMID- 29642657
TI  - Exploring Demographic and Environmental Factors Related to Unintentional
      Pesticide Poisonings in Children and Adolescents in Texas.
AB  - There is limited literature on the frequency and distribution of pesticide
      exposures, specifically with respect to demographic and environmental factors in
      the United States. The purpose of this exploratory study was to investigate
      geographic trends and factors associated with unintentional pesticide exposures
      in children and adolescents in Texas. The study used an ecological design with
      secondary data. A spatial scan statistic, based on a Poisson regression model,
      was employed to identify spatial clusters of unintentional pesticide-related
      poison center exposures. Next, logistic regression models were constructed to
      identify potential demographic and environmental factors associated with
      unintentional pesticide-related poison center exposures. There were 59,477
      unintentional pesticide-related poison center exposures from 2000 to 2013. The
      spatial scan statistic found a change in the number of counties in the identified
      clusters (e.g. , aggregation of counties with higher than expected exposures) for
      two time periods (2000-2006; 2007-2013). Based on the logistic regression models,
      factors associated with unintentional pesticide-related poison center exposures
      were percent black or African American population, year structure built, and
      percent moved in the past 12 months. In conclusion, this study found certain
      demographic and environmental factors may be associated with unintentional
      pesticide-related poison center exposures. Through understanding trends and
      associated factors, public health professionals can design interventions for
      populations at higher risk of pesticide exposures. This study also supports the
      use of spatial methods being utilized to expand upon current analysis of poison
      center data. Future research should confirm and build upon these findings.

PMID- 29642658
TI  - Evaluation of the Exposure to Environmental Pollutants Emanating from National
      Industrial Complexes.
AB  - The industrial complexes built during the course of economic development in South
      Korea played a pivotal role in the country's rapid economic growth. However, this
      growth was accompanied by health problems due to the pollutants released from the
      industrial complexes inevitably located near residential areas, given the limited
      land area available in South Korea. This study was conducted to evaluate the
      exposure to each pollutant emanating from industrial complexes for residents
      living in nearby areas, and to determine the substances requiring priority
      attention in future surveys. Pollutants were comprehensively categorized
      according to their emission and exposure levels based on data previously
      collected from the study areas. The emission, ambient concentration, and
      biomarker concentration levels of major pollutants emitted from eight national
      industrial complexes (Ulsan, Pohang, Gwangyang, Yeosu, Chungju, Daesan, Sihwa,
      and Banwol) were determined and tabulated. Each of the values was compared with
      the national/local average values, reference values, or control area
      concentrations depending on availability. Substances with completed exposure
      pathways and with high values for emissions, ambient concentrations, and
      biomarker concentrations were considered the substances posing exposure risks to
      the residents living near the corresponding industrial complex. The substances
      requiring continuous monitoring or supplementary exposure investigation were also
      categorized and presented. Lead and benzene had higher values for emissions,
      ambient concentrations, and biomarker concentrations in the Ulsan Industrial
      Complex area; thus, they were most likely to pose exposure risks to residents
      living in the area's neighborhoods. In other areas, styrene, xylene, cadmium,
      nitrogen oxide, trichloroethylene, nickel, manganese, and chromium required
      continuous monitoring, and arsenic, nickel, manganese, and chromium required
      biomarker measurements. In conclusion, the substances identified and categorized
      in this study need to be given appropriate attention in future surveys on
      exposure risks and health effects related to industrial complexes.

PMID- 29642659
TI  - In vitro evaluation of Rhus succedanea extracts for ruminants.
AB  - OBJECTIVE: This study was conducted to evaluate the effects of Rhus succedanea
      extract addition on in vitro ruminal fermentation and microbial growth. METHODS:
      Two ruminally-fistulated steers consuming 600 g/kg timothy- and 400 g/kg cracked
      corn-based concentrate with free access to water and mineral block were used as
      rumen fluid donors. In vitro batch fermentation, with timothy as a substrate, was
      conducted for up to 72 h, with Rhus succedanea extracts added to achieve final
      concentrations of 0, 10, 30, 50, 70, and 90 mg/L. RESULTS: Effective dry matter
      (DM) degradability rate linearly decreased (p = 0.046) depending on extract
      dosing levels. Total gas production after 24 to 72 h incubation tended to
      decrease following extract addition, beginning with 50 mg/L starting dose
      (significance of quadratic effects: p = 0.006, p<0.001, and p = 0.008 for 24, 48,
      and 72 h, respectively). Methane production decreased depending on dosing levels
      following 24 h (p<0.05) and 48 h (p<0.005) incubations and was the lowest with
      the 50 mg/L dose. The Rhus succedanea extracts increased the abundance of
      Fibrobacter succinogenes (p<0.05) and Ruminococcus flavefaciens (p = 0.0597) and
      decreased the abundance of methanogenic archaea (p<0.05) following 24 h
      incubation. CONCLUSION: Rhus succedanea was shown to reduce methane production
      and increase cellulolytic bacteria without any signs of toxic effects and with a
      minor effect on DM degradability.

PMID- 29642660
TI  - Digestibility, ruminal fermentation, and nitrogen balance with various feeding
      levels of oil palm fronds treated with Lentinus sajor-caju in goats.
AB  - OBJECTIVE: This study was an attempt to investigate the effect of levels of
      fungal (Lentinus sajor-caju) treated oil palm fronds (FTOPF) on digestibility,
      rumen fermentation, and nitrogen balance in goats. METHODS: Four 16 month old
      male crossbred (Thai Native*Anglo Nubian) goats with initial body weights of
      33.5+/-1.7 kg were randomly assigned according to a 4*4 Latin square design. Four
      levels of FTOPF were assigned for feed intake. The experimental treatments
      consisted of 0%, 33%, 67%, and 100% of oil palm fronds (OPF) being replaced by
      FTOPF. RESULTS: The results revealed that total dry matter intake and nutrient
      intake were not influenced (p>0.05) by the inclusion of FTOPF. However, the
      efficiency values of the digestibility of the dry matter, organic matter, crude
      protein, neutral detergent fiber, acid detergent fiber, and acid detergent lignin
      on FTOPF were higher (p<0.05) in treatments with 33%, 67%, and 100% of FTOPF
      compared with 0% of FTOPF. FTOPF feeding did not change the rumen pH,
      temperature, and NH3-N. However, the FTOPF levels did affect the total volatile
      fatty acid (VFA), molar proportion of acetate, propionate, butyrate, ratio of
      acetic (propionic acid and acetic) plus butyric (propionic acid), and production
      of CH4. The totals of VFA and propionate was lower in goat fed with 0% of FTOPF
      than in those of the other groups (p<0.05). The amount of nitrogen retention
      based on g/d/animal or the percentage of nitrogen retained was the lowest the
      goat fed with 0% of FTOPF (p<0.05), whereas nitrogen intake, excretion, and
      absorption were not changed among treatments. CONCLUSION: Based on this study,
      FTOPF could be effectively used as an alternative roughage source in total mixed
      ration diets, constituting at least up to 100% of OPF.

PMID- 29642661
TI  - Genetic characterization and population structure of six brown layer pure lines
      by using microsatellite markers.
AB  - Objective: The first stage in both breeding and programmes for the conservation
      of genetic resources are the identification of genetic diversity in the relevant
      population. The aim of the present study is to identify genetic diversity of six
      brown layer pure chicken lines (Rhode Island Red (RIRI, RIRII), Barred Rock
      (BARI, BARII), Columbian Rock (COL) and Line 54 (L-54)) with microsatellite
      markers. Furthermore, the study aims to employ its findings to discuss the
      possibilities for the conservation and sustainable use of these lines that have
      been bred as closed populations for a long period of time. Methods: In the
      present study, a total number of 180 samples belonging to RIRI (n=30), RIRII
      (n=30), BARI (n=30), BARII (n=30), L-54 (n=30), and COL (n=30) lines were
      genotyped through the use of 22 microsatellite loci. Microsatellite markers are
      extremely useful tools in the identification of genetic diversity owing to
      distributed throughout the eukaryotic genome in multitudes, they demonstrate co
      dominant inheritance; and they feature a high rate of polymorphism and
      repeatability. Results: In this study found all loci to be polymorphic and
      identified the average number of alleles per locus to be in the range between
      4.41 (BARI) and 5.45 (RIRI); the observed heterozygosity to be in the range
      between 0.31 (RIRII) and 0.50 (BARII); and FIS values in the range between 0.16
      (L-54) and 0.46 (RIRII). The FIS values obtained in this context points out to a
      deviation from Hardy-Weinberg equilibrium due to heterozygote deficiency in six
      different populations. The Neighbour-Joining tree, Factorial Correspondence
      Analysis and STRUCTURE clustering analyzes showed that six brown layer lines were
      separated according to their genetic origins. Conclusion: The results obtained
      from the study indicate a medium level of genetic diversity, high level
      inbreeding in chicken lines and high level genetic differentiation between
      chicken lines.

PMID- 29642662
TI  - Current situation and future prospects for the Australian beef industry - A
      review.
AB  - Beef production extends over almost half of Australia, with about 47,000 cattle
      producers that contribute about 20% ($A12.7 billion gross value of production) of
      the total value of farm production in Australia. Australia is one of the world's
      most efficient producers of cattle and was the world's third largest beef
      exporter in 2016. The Australian beef industry had 25 million head of cattle in
      2016-17, with a national beef breeding herd of 11.5 million head. Australian beef
      production includes pasture-based cow-calf systems, a backgrounding or grow-out
      period on pasture, and feedlot or pasture finishing. Feedlot finishing has
      assumed more importance in recent years to assure the eating quality of beef
      entering the relatively small Australian domestic market, and to enhance the
      supply of higher value beef for export markets. Maintenance of Australia's
      preferred status as a quality assured supplier of high value beef produced under
      environmentally sustainable systems from 'disease-free' cattle is of highest
      importance. Stringent livestock and meat quality regulations and quality
      assurance systems, and productivity growth and efficiency across the supply chain
      to ensure price competiveness, are crucial for continued export market growth in
      the face of increasing competition. Major industry issues, that also represent
      research, development and adoption priorities and opportunities for the
      Australian beef industry have been captured within exhaustive strategic planning
      processes by the red meat and beef industries. At the broadest level, these
      issues include consumer and industry support, market growth and diversification,
      supply chain efficiency, productivity and profitability, environmental
      sustainability, and animal health and welfare. This review provides an overview
      of the Australian beef industry including current market trends and future
      prospects, and major issues and opportunities for the continued growth,
      development and profitability of the industry.

PMID- 29642663
TI  - Association of leptin, toll-like receptor 4, and chemokine receptor of
      interleukin 8 C-X-C motif single nucleotide polymorphisms with fertility traits
      in Czech Fleckvieh cattle.
AB  - OBJECTIVE: The use of genetic markers can help to enhance reproduction in cattle,
      which is a very important trait for profitability in dairy production systems.
      This study evaluated the association between genotypes of leptin (LEP), toll-like
      receptor 4 (TLR4), and chemokine receptor of interleukin 8 C-X-C motif (CXCR1)
      genes and fertility traits in Czech Fleckvieh cattle. METHODS: Phenotypic data
      from 786 Czech Fleckvieh cows raised on 5 farms in the Czech Republic were used,
      along with information from the 1st three parities. To determine genotype, the
      polymerase chain reaction- restriction fragment length polymorphism method was
      used. RESULTS: Except for LEP g.-963C>T, all studied genotype frequencies of
      single nucleotide polymorphisms (SNPs) were distributed according to the Hardy
      Weinberg equilibrium. Two LEP SNPs (g.-963C>T and c.357C>T) were associated with
      the age at the 1st calving, days open (DO), pregnancy rate after 1st service
      (PR), and calving interval (CLI). In LEP g.-963C>T the TT genotype heifers
      firstly calved 24 days earlier than CC genotype and the CT genotype cow showed a
      tendency for shorter DO and higher PR. In LEP c.357C>T we observed longer CLI and
      DO period in TT cows. In general, we can propose the TT genotype of g.-963C>T as
      favorable and the TT genotype of c.357C>T as unfavorable for a cow's fertility.
      Heterozygotes in TLR4 c.-226C>G were significantly associated with shorter CLI,
      and presented a nonsignificant tendency to be associated with higher PR. In CXCR1
      c.777 C>G, we did not observe any relationship of this SNP with reproduction.
      CONCLUSION: Overall, the results showed that LEP could be an effective marker for
      improving reproduction in Czech Fleckvieh cattle. This study also provides novel
      insights into the relationship between TLR4 and CXCR1 SNPs and reproduction in
      dual-purpose cattle.

PMID- 29642664
TI  - Improving quality of common reed (Phragmites communis Trin.) silage with
      additives.
AB  - OBJECTIVE: Common reed (Phragmites communis Trin.) could potentially provide an
      alternative resource for silage; however, its silage quality is poor. The aim of
      this study was to investigate the factors in reed that contribute to poor quality
      and determine how the use of additives at ensiling could improve fermentation
      quality. METHODS: In Experiment 1, we determined the chemical composition and the
      presence of indigenous lactic acid bacteria (LAB) in reed. We further examined
      fermentation quality of reed silage under conditions without additives (NA) and
      treated glucose (G), lactic acid bacteria (L), and their combination (G+L). In
      Experiment 2, silage of NA, and with an addition of cellulase and lactic acid
      bacteria (CL) were prepared from harvested reed. The harvested reeds were
      fertilized at nitrogen concentrations of 0, 4, 8, and 12 g N/m2 and were
      harvested thrice within one year. RESULTS: The indigenous LAB and fermentable
      carbohydrates are at extremely low concentrations in reed. Reed silage, to which
      we added G+L, provided the highest quality silage among treatments in Experiment
      1. In Experiment 2, N fertilization had no negative effect on silage quality of
      reed. The harvest times decreased fermentable carbohydrate content in reed. The
      CL treatment provided a higher lactic acid content compared to the NA treatment.
      However, the quality of CL treated silage at the second and third harvests was
      significantly lower than at the first harvest, due to a reduction in
      carbohydrates caused by frequent harvesting. CONCLUSION: The causes of poor
      quality in reed silage are its lack of indigenous LAB and fermentable
      carbohydrates and its high moisture content. In addition, reed managed by
      frequent harvesting reduces carbohydrate content. Although the silage quality
      could be improved by adding CL, higher-quality silage could be prepared by adding
      fermentable carbohydrates, such as glucose (rather than adding cellulases).

PMID- 29642665
TI  - Fatty acid composition of goose meat depending on genotype and sex.
AB  - Objective: The aim of this study was to compare male and female geese of two
      contrasting genotypes in terms of fatty acid composition, indexes related to
      human health, lipid metabolism and oxidative stability of the meat. Methods: The
      experiment was carried out on total of 120 geese of two different genotypes; the
      native breed Czech Goose (CG) and commercial hybrid Novohradska Goose (NG). One-d
      old goslings were divided into 4 groups according to genotype and sex, and 8
      birds from each group were slaughtered at 8 weeks of age. Results: The effects of
      the interactions between genotype and sex were observed on growth performance and
      carcass traits. Final live weight (P < 0.001), daily weight gain (P < 0.001),
      daily feed intake (P < 0.001), slaughter weight (P < 0.001) and cold carcass
      weight (P < 0.001) were highest in NG males and lowest in CG females. The meat
      fatty acid composition results showed effects of both genotype and sex on the
      total n-6 and the total PUFA content, as well as the PUFA n-6/PUFA n-3 ratio.
      Regarding genotype, the total n-6, the total PUFA content and the PUFA n-6/PUFA n
      3 ratio were higher in CG, and higher values were found in females. In terms of
      the lipid metabolism, Delta5 - Delta6 desaturase (P = 0.006) was higher in males.
      The meat oxidative stability results revealed an interaction between genotype,
      sex and storage time (P < 0.001). The highest (13.85 mg/kg) malondialdehyde
      content was measured in the meat of CG females after 5 days of storage and was
      presumably related to a higher PUFA content. Conclusions: NG had a relatively
      higher growth rate and meat oxidative stability, whereas the advantage of CG meat
      is its favourable fatty acid profile characterized by a higher PUFA content.

PMID- 29642666
TI  - Expression of selenium-independent glutathione peroxidase 5 (GPx5) in the
      epididymis of Small Tail Han sheep.
AB  - OBJECTIVE: Selenium-independent glutathione peroxidase (GPx5) is specifically
      expressed in the mammalian epididymis and plays an important role in protecting
      sperm from reactive oxygen species and lipid peroxidation damage. This study
      investigates GPx5 expression in the epididymis of Small Tail Han sheep. METHODS:
      GPx5 expression was studied in three age groups: lamb (2 to 3 months), young (8
      to 10 months), and adult (18 to 24 months). The epididymis of each age group
      divided into caput, corpus and cauda, respectively. Analysis the expression
      quantity of GPx5 in epididymis and testis by real-time fluorescent quantitative
      polymerase chain reaction and Western blot. Finally, GPx5 protein locating in the
      epididymis by immunohistochemical. RESULTS: The results demonstrate that in the
      lamb group, the GPx5 mRNA, but not protein, can be detected. GPx5 mRNA and
      expressed protein were detected in both the young and adult groups. Moreover,
      both the mRNA and protein levels of GPx5 were significantly higher in the young
      group than in other two groups. When the different segments of epididymis were
      investigated, GPx5 mRNA was expressed in each segment of epididymis regardless of
      age. Additionally, the mRNA level in the caput was significantly higher than that
      in corpus and cauda within same age group. The GPx5 protein was in the epithelial
      cells' cytoplasm. However, GPx5 mRNA and protein were not detected in the testis.
      CONCLUSION: These results suggest that GPx5 is mainly expressed in the epididymis
      of Small Tail Han sheep, and that the expression level of GPx5 is associated with
      age. Additionally, GPx5 was primarily expressed in the epithelial cells of the
      caput. Taken together, these studies indicate that GPx5 is expressed in the
      epididymis in all age grades.

PMID- 29642667
TI  - Mitochondrial tumor suppressor 1 is a target of AT-rich interactive domain 1A and
      progesterone receptor in the murine uterus.
AB  - Objective: Progesterone receptor (PGR) and AT-rich interactive domain 1A (ARID1A)
      have important roles in the establishment and maintenance of pregnancy in the
      uterus. In present studies, we examined the expression of mitochondrial tumor
      suppressor 1 (MTUS1) in the murine uterus during early pregnancy as well as in
      response to ovarian steroid hormone treatment. METHODS: We performed quantitative
      reverse transcription polymerase chain reaction and immunohistochemistry analysis
      to investigate the regulation of MTUS1 by ARID1A and determined expression
      patterns of MTUS1 in the uterus during early pregnancy. RESULTS: The expression
      of MTUS1 was detected on day 0.5 of gestation (GD 0.5) and then gradually
      increased until GD 3.5 in the luminal and glandular epithelium. However, the
      expression of MTUS1 was significantly reduced in the uterine epithelial cells of
      Pgrcre/+Arid1af/f and Pgr knockout (PRKO) mice at GD 3.5. Furthermore, MTUS1
      expression was remarkably induced after P4 treatment in the luminal and glandular
      epithelium of the wild-type mice. However, the induction of MTUS1 expression was
      not detected in uteri of Pgrcre/+Arid1af/f or PRKO mice treated with P4.
      CONCLUSION: These results suggest that MTUS1 is a novel target gene by ARID1A and
      PGR in the uterine epithelial cells.

PMID- 29642668
TI  - Effect of increasing levels of apparent metabolizable energy on laying hens in
      barn system.
AB  - OBJECTIVE: This experiment was to investigate the effect of increasing levels of
      apparent metabolizable energy (AMEn) on the laying performance, egg quality,
      blood parameters, blood biochemistry, intestinal morphology, and apparent total
      tract digestibility (ATTD) of energy and nutrients in diets fed to laying hens.
      METHODS: A total of three-hundred twenty 33-week-old Hy-Line Brown laying hens
      (Gallus domesticus) were evenly assigned to four experimental diets of 2,750,
      2,850, 2,950, and 3,050 kcal AMEn/kg in pens with floors covered with deep litter
      of rice hulls. There were four replicates of each treatment, each consisting of
      20 birds in a pen. RESULTS: AMEn intake was increased (linear, p<0.05) with
      inclusion level of AMEn in diets increased. Feed intake and feed conversion ratio
      were improved (linear, p<0.01), but hen-day egg production tended to be increased
      with an increasing level of AMEn in diets. During the experiment, leukocyte
      concentration and blood biochemistry (total cholesterol, triglyceride, glucose,
      total protein, calcium, asparate aminotransferase, and alanine transferase were
      not influenced by increasing level of AMEn in diets. Gross energy and ether
      extract were increased (linear, p<0.01) as the inclusion level of AMEn in diets
      increased. CONCLUSION: Laying hens fed high AMEn diet (i.e., 3,050 kcal/kg in the
      current experiment) tended to overconsume energy with a positive effect on feed
      intake, feed conversion ratio, nutrient digestibility, and intestinal morphology
      but not on egg production and egg mass.

PMID- 29642669
TI  - Evaluation of polyherbal formulation and synthetic choline chloride on choline
      deficiency model in broilers: implications on zootechnical parameters, serum
      biochemistry and liver histopathology.
AB  - OBJECTIVE: The study was designed to establish choline deficiency model (CDM) in
      broilers for evaluating efficacy of polyherbal formulation (PHF) in comparison
      with synthetic choline chloride (SCC). METHODS: A total of 2,550 one-day-old Cobb
      430 broiler chicks were randomly assigned to different groups in three
      experiments. In experiment 1, G1 and G2 served as normal controls and were fed a
      basal diet with 100% soybean meal (SBM) as a major protein source supplemented
      with and without SCC, respectively. In G3, G4, G5, and G6 groups, SBM was
      replaced at 25%, 50%, 75%, and 100% by soy protein isolate (SPI) to induce a
      graded level of choline deficiency. In experiment 2, PHF (500 and 1,000 g/ton) in
      comparison with SCC (1,000 g/ton) were evaluated. In experiment 3, dose-response
      of PHF (200, 400, and 500 g/ton) with SCC (400 g/ton) was determined. RESULTS:
      Replacement of SBM by SPI produced a linear decrease in body weight gain (BWG)
      with a poor feed conversion ratio (FCR). 25% SBM replacement by SPI yielded an
      optimum negative impact on BWG and FCR; hence, it is considered for further
      studies. In experiment 2, PHF (500 and 1,000 g/ton) and SCC (1,000 g/ton) showed
      a similar performance in BWG, FCR and relative liver weight. In experiment 3, PHF
      produced an optimum efficacy at 400 g/ton and was comparable to SCC in the
      restoration of serum aspartate aminotransferase activity, abdominal fat, breast
      muscle lipid content and liver histopathological abnormalities. CONCLUSION:
      Replacement of SBM by SPI caused choline deficiency characterised by worsening of
      BWG, FCR, elevation in liver enzymes and histopathological changes indicating
      fatty liver. CDM was found valid for evaluating SCC and PHF. It is concluded that
      PHF has the potential to mimic biological activities of SCC through the
      restoration of negative effects caused by CDM.

PMID- 29642670
TI  - Effects of dietary supplementation with fermented and non-fermented brown algae
      by-products on laying performance, egg quality, and blood profile in laying hens.
AB  - OBJECTIVE: This study was conducted to investigate the effects of dietary
      supplementation with fermented and non-fermented brown algae by-products on the
      laying performance, egg quality, relative organ weight, and blood profile of
      laying hens. METHODS: Hy-Line Brown chickens (n = 180; 70-week-old) were randomly
      divided into 5 groups with 4 replicates per group (3 hens per cage, 4 cages per
      replicate), and fed with 5 experimental diets, namely the basal control diet
      (CON) or the control diet supplemented with 0.5% brown seaweed (BS), 0.5% seaweed
      fusiforme (SF), 0.5% fermented brown seaweed (FBS), or 0.5% fermented seaweed
      fusiforme (FSF), for 4 weeks. RESULTS: Egg production rate and egg mass were
      greater in the BS group than in the other groups (p<0.05), and the SF and FSF
      groups had greater egg production than the control group (p<0.05). Egg weight was
      higher in the BS group than in the other groups (p<0.05). There were no
      differences in eggshell color, egg yolk color, eggshell strength, or eggshell
      thickness among the groups. There was no difference in Haugh units among the
      treatment groups, except for the FSF group, which had a significantly lower value
      (p<0.05). The non-fermented groups had greater relative organ weights,
      particularly the liver and cecum, than the other groups (p<0.05). Regarding blood
      profile, the supplemented-diet groups had higher albumin levels than the control
      group (p<0.05). The FBS group had higher total cholesterol and triglyceride
      levels than the other groups (p<0.05). The BS and FBS groups had higher glutamic
      pyruvic transaminase levels than the other groups (p<0.05). CONCLUSION: This
      study demonstrated that dietary brown algae supplementation can improve egg
      laying performance; however, supplementation with fermented seaweeds had no
      positive effect on the egg-laying performance of hens.

PMID- 29642671
TI  - Effects of different amylose to amylopectin ratios on rumen fermentation and
      development in fattening lambs.
AB  - OBJECTIVE: The objective of this experiment was to examine the effects of
      different amylose/amylopectin ratios on rumen fermentation and development of
      fattening lambs. METHODS: Forty-eight 7-day-old male Small-tailed Han
      sheep*Northeast fine wool sheep were randomly assigned to four treatments of
      dietary amylose/amylopectin ratios (0.12, 0.23, 0.24, and 0.48 in tapioca starch,
      corn starch, wheat starch and pea starch diets, respectively). Three lambs from
      each treatment were slaughtered at 21, 35, 56, and 77 days of age to determine
      the rumen fermentation and development. RESULTS: Compared with tapioca starch
      diet, the pea starch diet significantly increased the concentration of ammonia
      nitrogen in the ruminal fluid of lambs but significantly decreased the bacterial
      protein content. At 56 and 77 d, the rumen propionate concentration tended to be
      greatest in the tapioca starch group than in other groups. The rumen butyrate
      concentration was the greatest in lambs fed on pea starch compared with those fed
      on other starch diets. Furthermore, the pea starch diet significantly stimulated
      rumen development by increasing the papillae height, width and surface area in
      the rumen ventral or dorsal locations in lambs. However, different
      amylose/amylopectin ratios diets did not significantly affect the feed intake,
      body weight, average daily gain, the relative weight and capacity of the rumen in
      lambs with increasing length of trial periods. CONCLUSION: Lambs early
      supplemented with a high amylose/amylopectin ratio diet had favourable
      morphological development of rumen epithelium, which was not conducive to
      bacterial protein synthesis.

PMID- 29642672
TI  - Phytochemicals and antioxidant capacity of some tropical edible plants.
AB  - OBJECTIVE: To find biological functions such as antibacterial and antioxidant
      activities in several tropical plants and to investigate the possibility of
      antibiotic substitute agents to prevent and treat diseases caused by pathogenic
      bacteria. METHODS: Plants such as Poncirus trifoliata fruit (Makrut), Zingiber
      officinale Rosc (Khing), Areca catechu L. (Mak), Solanum melongena L. I
      (Makkhuayao), and Solanum melongena L. II (Makhurapro) were extracted by
      methanol, n-hexane, chloroform, ethyl acetate, butanol and water. The free
      radical scavenging activities were measured using 2-diphenyl-2-picryl hydrazyl
      photometric assay. Antibacterial activities with a minimum inhibitory
      concentration (MIC) were observed by agar diffusion assay against pathogenic
      strains of Escherichia coli, Burkholderia sp., Haemopilus somnus, Haemopilus
      parasuis, Clostridium perfringens, and Pantoea agglomerans. RESULTS: Poncirus
      trifoliata fruit methanol extract showed antibacterial activities against gram
      negative and gram-positive pathogens. Additionally, this showed the strongest
      antibacterial activity against Burkholderia sp. and Haemopilus somnus with MIC
      131 MUg/mL, respectively. Areca catechu L. water extract showed antibacterial
      activities against Burkholderia sp., Haemopilus somnus, and Haemopilus parasuis.
      The MIC value for Haemopilus parasuis was 105 MUg/mL in this. Antioxidant
      activity of Zingiber officinale Rosc n-hexane extract showed 2.23 mg/mL effective
      concentration 50% (EC50) value was the highest activity among tropical plants
      extracts. Total polyphenol content in Zingiber officinale Rosc methanol extract
      was 48.4 MUg/mL and flavonoid content was 22.1 MUg/mL showed the highest values
      among tested plants extracts. CONCLUSION: Taken together, these results suggest
      that tropical plants used in this study may have a potential benefit as an
      alternative antibiotics agent through their antibacterial and antioxidant
      activities.

PMID- 29642673
TI  - The use of data mining methods for dystocia detection in Polish Holstein-Friesian
      Black-and-White cattle.
AB  - OBJECTIVE: The aim of this study was to verify the usefulness of artificial
      neural networks (ANN), multivariate adaptive regression splines (MARS), naive
      Bayes classifier (NBC), general discriminant analysis (GDA), and logistic
      regression (LR) for dystocia detection in Polish Holstein-Friesian Black-and
      White heifers and cows and to indicate the most influential predictors of calving
      difficulty. METHODS: A total of 1,342 and 1,699 calving records including six
      categorical and four continuous predictors were used. Calving category (difficult
      vs easy or difficult, moderate and easy) was the dependent variable. RESULTS: The
      maximum sensitivity, specificity and accuracy achieved for heifers on the
      independent test set were 0.855 (for ANN), 0.969 (for NBC), and 0.813 (for GDA),
      respectively, whereas the values for cows were 0.600 (for ANN), 1.000 and 0.965
      (for NBC, GDA, and LR), respectively. With the three categories of calving
      difficulty, the maximum overall accuracy for heifers and cows was 0.589 (for
      MARS) and 0.649 (for ANN), respectively. The most influential predictors for
      heifers were an average calving difficulty score for the dam's sire, calving age
      and the mean yield of the farm, where the heifer was kept, whereas for cows,
      these additionally included: calf sex, the difficulty of the preceding calving,
      and the mean daily milk yield for the preceding lactation. CONCLUSION: The
      potential application of the investigated models in dairy cattle farming
      requires, however, their further improvement in order to reduce the rate of
      dystocia misdiagnosis and to increase detection reliability.

PMID- 29642675
TI  - Use of welfare outcome information in three types of dairy farm inspection
      reports.
AB  - OBJECTIVE: The aim of this study was to examine the use of outcome-based
      observations within Assured Dairy Farm scheme (ADF), Soil Association Organic
      Standards (SA), and cross compliance (CC) farm assessment reports. METHODS: A
      total of 449 ADF reports, 37 SA reports and 26 CC reports were analyzed and their
      objective comments categorized as either resource-based or outcome-based.
      RESULTS: A mean of 61.0% of ADF questions were responded to with comments, in
      comparison to 25.0% of SA and, 21.0% of CC report questions. The SA and CC
      reports had significantly more outcome-based comments than the ADF (p<0.001). The
      assessors' tendency of choosing resource-based approach was revealed in the
      questionnaire results. CONCLUSION: Generally, the comments were comprehensive and
      contained professional judgements. Large numbers of comments provided in the ADF
      reports were mostly compliant and resource-based evidence, which serves as proof
      of assessment rather than aiding the certifying process. The inclusion of
      specific welfare outcome measures in the SA inspection likely increased the use
      of outcome-based comments in the reports, irrespective of whether the farm
      achieved compliance with a given standards. The CC scheme, on the other hand,
      focused on providing outcome-based evidence to justify noncompliant decisions.

PMID- 29642674
TI  - Expression pattern of prohibitin, capping actin protein of muscle Z-line beta
      subunit and tektin-2 gene in Murrah buffalo sperm and its relationship with sperm
      motility.
AB  - OBJECTIVE: The aim of the current study is to investigate the relationship
      between prohibitin (PHB), capping actin protein of muscle Z-line beta subunit
      (CAPZB), and tektin-2 (TEKT2) and sperm motility in Murrah buffalo. METHODS: We
      collected the high-motility and low-motility semen samples, testis, ovary,
      muscle, kidney, liver, brain and pituitary from Murrah buffalo, and analysed the
      expression of PHB, CAPZB, and TEKT2 in mRNA (message RNA) and protein level.
      RESULTS: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR)
      result showed that the expression of PHB was higher and CAPZB, TEKT2 were
      specifically expressed in testis as compared to the other 6 tissues, and that in
      testis, the expression of TEKT2 was higher than that of CAPZB and PHB.
      Immunohistochemistry test revealed that all three genes were located on the
      convoluted seminiferous tubule and enriched in spermatogenic cells. Both qRT-PCR
      and Western Blot results showed that the expression levels of PHB, CAPZB, and
      TEKT2 were significantly lower in the low-motility semen group compared to the
      high-motility semen group (p<0.05). CONCLUSION: The expression levels of PHB,
      CAPZB, and TEKT2 in Murrah buffalo sperm have a high positive correlation with
      sperm motility. And the three genes may be potential molecular markers for the
      decline of buffalo sperm motility.

PMID- 29642676
TI  - Can the body composition of crossbred dairy cattle be predicted by equations for
      beef cattle?
AB  - OBJECTIVE: The aim of the study was to evaluate the efficiency of the Hankins and
      Howe (HH46), Valadares Filho (V06), and Marcondes (M12) equations for predicting
      the physical and chemical composition of dairy crossbred bulls carcasses, as well
      as the chemical composition of their empty bodies. METHODS: This study was
      conducted using 30 dairy crossbred bulls. One group of five animals was
      slaughtered at the beginning of the experiment, and the remaining were
      slaughtered 112 days later. Animals were distributed in a completely randomized
      design into treatments consisting different levels of concentrate (0%, 17%, 34%,
      51%, and 68%). The physical and chemical compositions of the cattle were obtained
      from the right half of the carcass and using samples taken between the 9th and
      11th ribs of the left half of the carcass. The estimated and experimentally
      determined values were compared using the correlation and concordance
      coefficient, as well as the mean square error of prediction (MSEP) and its
      components. RESULTS: The HH46 equations were better at estimating the amount of
      muscle plus fat in the carcass. The amount of bone in the carcasses could not be
      well estimated by the HH46 and M12 models. The M12, HH46, and V06 equations were
      worst at estimating the amounts of protein, ether extract, and water in the
      carcass, respectively. In the empty body, the amounts of protein and water were
      well estimated by the HH46 equations. Protein, ether extract, and water were
      accurately estimated by the V06 equations, and ether extract by the M12
      equations. CONCLUSION: The physical and chemical composition of dairy crossbred
      bull carcasses, as well as the chemical composition of their empty bodies, can be
      predicted using the equations tested here. The amount of bone in these carcasses
      could not be accurately predicted.

PMID- 29642677
TI  - Selection response and estimation of the genetic parameters for multidimensional
      measured breast meat yield related traits in a long-term breeding Pekin duck
      line.
AB  - OBJECTIVE: This study was conducted to estimate the genetic parameters and
      breeding values of breast meat related traits of Pekin ducks. Selection response
      was also determined by using ultrasound breast muscle thickness (BMT)
      measurements in combination with bosom breadth (BB) and keel length (KL) values.
      METHODS: The traits analyzed were breast meat weight (BMW), body weight (BW),
      breast meat percentage (BMP) and the three parameters of breast meat (BB, KL, and
      BMT). These measurements were derived from studying 15,781 Pekin ducks selected
      from 10 generations based on breast meat weight. Genetic parameters and breeding
      value were estimated for the analysis of the breeding process. RESULTS: Estimated
      heritability of BMW and BMP were moderate (0.23 and 0.16, respectively), and
      heritability of BW was high (0.48). Other traits such as BB, KL, and BMT
      indicated moderate heritability ranging between 0.11 and 0.28. Significant
      phenotypic correlations of BMW with BW and BMP were discovered (p<0.05), and
      genetic correlations of BMW with BW and BMP were positive and high (0.83 and
      0.66, respectively). It was noted that BMW had positive correlations with all the
      other traits. Generational average estimated breeding values of all traits
      increased substantially over the course of selection, which demonstrated that the
      ducks responded efficiently to increased breast meat yield after 10 generations
      of breeding. CONCLUSION: The results indicated that duck BMW had the potential to
      be increased through genetic selection with positive effects on BW and BMP. The
      ultrasound BMT, in combination with the measurement of BB and KL, is shown to be
      essential and effective in the process of high breast meat yield duck breeding.

PMID- 29642678
TI  - Polymorphisms of melatonin receptor genes and their associations with egg
      production traits in Shaoxing duck.
AB  - OBJECTIVE: In birds, three types of melatonin receptors (MTNR1A, MTNR1B, and
      MTNR1C) have been cloned. Previous researches have showed that three melatonin
      receptors played an essential role in reproduction and ovarian physiology.
      However, the association of polymorphisms of the three receptors with duck
      reproduction traits and egg quality traits is still unknown. In this test, we
      chose MTNR1A, MTNR1B, and MTNR1C as candidate genes to detect novel sequence
      polymorphism and analyze their association with egg production traits in Shaoxing
      duck, and detected their mRNA expression level in ovaries. METHODS: In this
      study, a total of 785 duck blood samples were collected to investigate the
      association of melatonin receptor genes with egg production traits and egg
      quality traits using a direct sequencing method. And 6 ducks representing two
      groups (3 of each) according to the age at first eggs (at 128 days of age or
      after 150 days of age) were carefully selected for quantitative real-time
      polymerase chain reaction. RESULTS: Seven novel polymorphisms (MTNR1A: g. 268C>T,
      MTNR1B: g. 41C>T, and g. 161T>C, MTNR1C: g. 10C>T, g. 24A>G, g. 108C>T, g. 363
      T>C) were detected. The single nucleotide polymorphism (SNP) of MTNR1A (g.
      268C>T) was significantly linked with the age at first egg (p<0.05). And a
      statistically significant association (p<0.05) was found between MTNR1C g.108 C>T
      and egg production traits: total egg numbers at 34 weeks old of age and age at
      first egg. In addition, the mRNA expression level of MTNR1A in ovary was
      significantly higher in late-mature group than in early-mature group, while
      MTNR1C showed a contrary tendency (p<0.05). CONCLUSION: These results suggest
      that identified SNPs in MTNR1A and MTNR1C may influence the age at first egg and
      could be considered as the candidate molecular marker for identify early maturely
      traits in duck selection and improvement.

PMID- 29642679
TI  - Effects of dietary supplementation with a combination of plant oils on
      performance, meat quality and fatty acid deposition of broilers.
AB  - OBJECTIVE: This study was to evaluate effects of mixed plant oils (identified as
      mixed oil 1 [MO1] and mixed oil 2 [MO2]) on performance, serum composition,
      viscera percentages, meat quality, and fatty acid deposition of broilers.
      METHODS: A total of 126 one-day-old Arbor Acres male broiler chicks (weighing
      44.91+/-0.92 g) were randomly allocated to 1 of 3 treatments with 7 replicate
      pens per treatment (6 broilers per pen). Dietary treatments included a corn
      soybean basal diet supplemented with 3% soybean oil (CTR), basal diet with 3% MO1
      (a mixture of 15% corn oil, 10% coconut oil, 15% linseed oil, 20% palm oil, 15%
      peanut oil and 25% soybean oil; MO1), or basal diet with 3% MO2 (a combination of
      50% MO1 and 50% extruded corn; MO2). The trial consisted of phase 1 (d 1 to 21)
      and phase 2 (d 22 to 42). RESULTS: Compared to CTR, broilers fed MO (MO1 or MO2)
      had greater (p<0.05) average daily gain in phase 1, 2, and overall (d 1 to 42),
      redness in thigh muscle, concentrations of serum glucose, serum albumin,
      saturated fatty acids (SFA) and n-6/n-3 polyunsaturated fatty acids (PUFA) ratio
      in breast muscle, while these broilers also showed lower (p<=0.05) drip loss and
      concentrations of C18:3n-3 and PUFA/SFA ratio in breast muscle. Broilers fed MO2
      had higher (p<0.05) liver percentage, while broilers fed MO1 had lower (p<=0.05)
      feed conversion ratio in phase 1 and increased (p<0.05) contents of C18:2n-6,
      C20:5n-3, C22:6n-3, and n-3 PUFA in breast muscle compared to CTR. CONCLUSION:
      Mixed plant oils had positive effects on performance, serum parameters, meat
      quality, liver percentage and fatty acid deposition in broilers, which indicates
      they can be used as better dietary energy feedstocks than soybean oil alone.

PMID- 29642680
TI  - Effect of probiotics and xylo-oligosaccharide supplementation on nutrient
      digestibility, intestinal health and noxious gas emission in weanling pigs.
AB  - OBJECTIVE: This study was conducted to evaluate the effect of probiotics
      (Bacillus subtilis and Enterococcus faecium) and xylo-oligosaccharide (XOS)
      supplementation on growth performance, nutrient digestibility, serum profiles,
      intestinal health, fecal microbiota and noxious gas emission in weanling pigs.
      METHODS: A total of 240 weanling pigs ([Yorkshire*Landrace]*Duroc) with an
      average body weight (BW) of 6.3+/-0.15 kg were used in this 28-day trial. Pigs
      were randomly allocated in 1 of the following 4 dietary treatments in a 2*2
      factorial arrangement with 2 levels of probiotics (0 and 500 mg/kg probiotics)
      and XOS (0 and 200 mg/kg XOS) based on the BW and sex. RESULTS: Administration of
      probiotics or XOS improved average daily gain (p<0.05) during 0 to 14 d and the
      overall period, while pigs that were treated with XOS had a greater average daily
      gain and feed efficiency (p<0.05) compared with unsupplemented treatments
      throughout 15 to 28 d and the whole experiment. Either probiotics or XOS
      treatments increased the apparent total tract digestibility of nutrients (p<0.05)
      during 0 to 14 d. No effects on serum profiles were observed among treatments.
      The XOS increased villus height: crypt depth ratio in jejunum (p<0.05). The
      supplementation of probiotics (500 mg/kg) or XOS (200 mg/kg) alone improved the
      apparent total tract digestibility of dry matter, nitrogen and gross energy on d
      14, the activity of trypsin and decreased fecal NH3 concentration (p<0.05).
      Administration of XOS decreased fecal Escherichia coli counts (p<0.05), while
      increased lactobacilli (p<0.05) on d 14. There was no interaction between dietary
      supplementation of probiotics and XOS. CONCLUSION: Inclusion of XOS at 200 mg/kg
      or probiotics (Bacillus subtilis and Enterococcus faecium) at 500 mg/kg in diets
      containing no antibiotics significantly improved the growth performance of
      weanling pigs. Once XOS is supplemented, further providing of probiotics is not
      needed since it exerts little additional effects.

PMID- 29642681
TI  - The effect of nutrition and body condition of triplet-bearing ewes during late
      pregnancy on the behaviour of ewes and lambs.
AB  - OBJECTIVE: Triplet-born lambs are less likely to survive to weaning than twin
      born or single-born lambs. Appropriate ewe-lamb bonding behaviours and lamb
      vigour behaviours are necessary for survival of lambs. The aim of this experiment
      was to determine whether maternal nutrition during late pregnancy influenced
      behaviour of the ewe and her lambs soon after birth, and to determine whether mid
      pregnancy body condition score (BCS) influenced any behavioural response.
      METHODS: The experiments included ewes that were in BCS 2.0, 2.5, or 3.0 in mid
      pregnancy and were fed either ad libitum or to pregnancy-maintenance requirements
      in late-pregnancy (day 115 until 136 in experiment one, and day 128 until 141 in
      experiment two). The time taken for lambs to stand, contact dam, suck from dam
      and follow dam was recorded three to 18 h after birth. The number of high- and
      low-pitched bleats emitted by the ewe and lambs was recorded, along with maternal
      behaviour score (MBS) of the ewe. Lambs in experiment two underwent a maternal
      recognition test at 12 or 24 h. RESULTS: There were significant effects of
      feeding treatment on bleating behaviour of ewes and lambs, but these were
      inconsistent among BCS groups and between experiments. Lamb vigour behaviours
      were not affected by feeding treatment. In experiment one, there was no effect of
      feeding treatment or BCS on MBS, but in experiment two, ewes in BCS3 in mid
      pregnancy had greater MBS than ewes in BCS2 in mid-pregnancy (MBS 3.1/5 vs MBS
      2.1/5; p<0.05). CONCLUSION: Given there were no repeatable effects on behaviour
      of ewes and lambs, ad libitum feeding rather than feeding for pregnancy
      maintenance requirements cannot be used to improve behaviours soon after birth of
      triplet-bearing ewes in BCS 2-3 and their lambs in extensive pastoral conditions.

PMID- 29642682
TI  - In vitro and in vivo evaluation of kenaf (Hibiscus cannabinus L.) as a roughage
      source for beef cattle.
AB  - OBJECTIVE: The goal of this study was to evaluate kenaf as a roughage source in
      vitro and its effects on meat quality of Hanwoo (Korean native) cattle. METHODS:
      Three roughage materials, rice straw silage, ryegrass silage, and kenaf silage,
      were tested in a batch culture and feeding trial. Rumen fermentation parameters,
      including gas, pH, volatile fatty acid (VFA), and ammonia were analyzed. In the
      feeding trial, Hanwoo steers (373.5+/-5.1 kg, n = 36, 11 month of age) were
      divided into three feeding groups (n = 12 each). Animals were fed with each
      silage and concentrate until the fattening stage. RESULTS: Crude protein, ether
      extract, and non-structural carbohydrates were greater in kenaf silage. Total gas
      production was higher in ryegrass silage, followed by kenaf silage and rice straw
      silage (p<0.05). Total VFA and individual VFA (acetate, propionate, and n
      butyrate) were greater in kenaf silage than rice straw silage (p<0.05). In vitro
      dry matter digestibility showed a similar trend to that of total gas and VFA
      production; it was higher in ryegrass silage and lower in rice straw (p<0.05).
      Throughout the feeding trial, the rice straw silage group showed significantly
      greater average daily gain than did the others (p<0.05). The feed conversion
      ratio in the group fed kenaf silage was significantly greater than that of others
      (p<0.05). No significant differences were observed in yield or quality traits,
      including carcass weight, ribeye area, backfat thickness, and scores for
      marbling, meat color, and fat color (p>0.05). CONCLUSION: The results indicated
      that no negative effects on growth performance and carcass characteristics
      occurred across treatments. Therefore, kenaf could be substituted for rice straw,
      which is most widely used as a roughage source in Korea.

PMID- 29642683
TI  - Effect of Lactobacillus salivarius on growth performance, diarrhea incidence,
      fecal bacterial population and intestinal morphology of suckling pigs challenged
      with F4+ enterotoxigenic Escherichia coli.
AB  - Objective: Gut health improvements were monitored with respect to growth
      performance, diarrhea incidence, fecal bacterial population and intestinal
      morphology of suckling pigs orally supplemented with live Lactobacillus
      salivarius (L. salivarius) oral suspensions and challenged with F4+
      enterotoxigenic Escherichia coli (ETEC). METHODS: Two groups of newborn pigs from
      18 multiparous sows were randomly designated as non-supplemented (control: n =
      114 piglets) and L. salivarius supplemented groups (treatment: n = 87 piglets).
      Treatment pigs were orally administered with 2 mL of 109 colony-forming unit
      (CFU)/mL L. salivarius on days 1 to 3, then they were orally administered with 5
      mL of 109 CFU/mL L. salivarius on days 4 to 10, while those in control group
      received an equal amount of phosphate buffered saline solution. On day 24 (2
      weeks post supplementation), one pig per replicate of both groups was orally
      administered with 108 CFU/mL F4+ ETEC, then they were euthanized on day 29 of
      experiment. RESULTS: Results revealed that pigs in treatment group had a
      statistically significant increase in average daily gain, body weight and weight
      gain, and tended to lower diarrhea throughout the study. Numbers of Lactobacillus
      population in feces of treatment pigs were higher than control pigs, especially
      on day 10 of study. Numbers of total bacteria in intestinal contents of control
      pigs were also increased, but not Coliform and Lactobacillus populations.
      Histological examination revealed statistically significant improvements of
      villous height and villous/crypt ratio of duodenum, proximal jejunum and distal
      jejunum parts of treatment pigs compared with controls. Duodenal pH of treatment
      group was significantly decreased. CONCLUSION: Oral supplementation of live L.
      salivarius during the first 10 days of suckling pig promoted growth performance
      and gut health, reduced diarrhea incidence, increased fecal Lactobacillus
      populations and improved intestinal morphology.

PMID- 29642684
TI  - Monitoring conservation effects on a Chinese indigenous chicken breed using major
      histocompatibility complex B-G gene and DNA Barcodes.
AB  - OBJECTIVE: We report monitoring conservation effect for a Chinese indigenous
      chicken (Langshan) breed using major histocompatibility complex (MHC) and DNA
      barcords. METHODS: The full length of MHC B-G gene and mitochondrial cytochrome
      oxidase I (COI) gene in generations 0, 5, 10, 15, 16, and 17 was measured using
      re-sequencing and sequencing procedures, respectively. RESULTS: There were 292
      single nucleotide polymorphisms of MHC B-G gene identified in six generations.
      Heterozygosity (He) and polymorphic information content (PIC) of MHC B-G gene in
      generations 10, 15, 16, and 17 remained stable. He and PIC of MHC B-G gene were
      different in six generations, with G10, G15, G16, G17 >G5>G0 (p<0.05). For the
      COI gene, there were five haplotypes in generations 0, 5, 10, 15, 16, and 17.
      Where Hap2 and Hap4 were the shared haplotypes, 164 individuals shared Hap2
      haplotypes, while Hap1 and Hap3 were the shared haplotypes in generations 0 and 5
      and Hap5 was a shared haplotype in generations 10, 15, 16, and 17. The sequence
      of COI gene in 6 generations was tested by Tajima's and D value, and the results
      were not significant, which were consistent with neutral mutation. There were no
      differences in generations 10, 15, 16, and 17for measured phenotypic traits. In
      other generations, for annual egg production, with G5, G10, G15, G16, G17>G0
      (p<0.05). For age at the first egg and age at sexual maturity, with G10, G15,
      G16, G17>G5>G0 (p<0.05). CONCLUSION: Combined with the results of COI gene DNA
      barcodes, MHC B-G gene, and phenotypic traits we can see that genetic diversity
      remained stable from generations 10 to 17 and the equimultiple random matching
      pedigrees conservation population conservation effect of Langshan chicken was
      effective as measured by these criteria.

PMID- 29642685
TI  - Variations in mitochondrial cytochrome b region among Ethiopian indigenous cattle
      populations assert Bos taurus maternal origin and historical dynamics.
AB  - OBJECTIVE: This study was carried out to assess the haplotype diversity and
      population dynamics in cattle populations of Ethiopia. METHODS: We sequenced the
      complete mitochondrial cytochrome b gene of 76 animals from five indigenous and
      one Holstein Friesian*Barka cross bred cattle populations. RESULTS: In the
      sequence analysis, 18 haplotypes were generated from 18 segregating sites and the
      average haplotype and nucleotide diversities were 0.7540+/-0.043 and 0.0010+/
      0.000, respectively. The population differentiation analysis shows a weak
      population structure (4.55%) among the populations studied. Majority of the
      variation (95.45%) is observed by within populations. The overall average pair
      wise distance (FST) was 0.049539 with the highest (FST = 0.1245) and the lowest
      (FST = 0.011) FST distances observed between Boran and Abigar, and Sheko and
      Abigar from the indigenous cattle, respectively. The phylogenetic network
      analysis revealed that all the haplotypes detected clustered together with the
      Bos taurus cattle and converged to a haplogroup. No haplotype in Ethiopian cattle
      was observed clustered with the reference Bos indicus group. The mismatch
      distribution analysis indicates a single population expansion event among the
      cattle populations. CONCLUSION: Overall, high haplotype variability was observed
      among Ethiopian cattle populations and they share a common ancestor with Bos
      taurus.

PMID- 29642686
TI  - Expression profiles of circular RNAs in sheep skeletal muscle.
AB  - OBJECTIVE: Circular RNAs (circRNAs) are a newfound class of non-coding RNA in
      animals and plants. Recent studies have revealed that circRNAs play important
      roles in cell proliferation, differentiation, autophagy and apoptosis during
      development. However, there are few reports about muscle development-related
      circRNAs in livestock. METHODS: RNA sequencing analysis was employed to identify
      and annotate circRNAs from longissimus dorsi of sheep. Reverse transcription
      followed by real-time quantitative (q) polymerase chain reaction (PCR) analysis
      verified the presence of these circRNAs. Targetscan7.0 and miRanda were used to
      analyse the interaction of circRNA-microRNA (miRNA). To investigate the function
      of circRNAs, an experiment was conducted to perform enrichment analysis hosting
      genes of circRNAs using gene ontology (GO) and Kyoto encyclopedia of genes and
      genomes (KEGG) pathways. RESULTS: About 75.5 million sequences were obtained from
      RNA libraries of sheep skeletal muscle. These sequences were mapped to 729 genes
      in the sheep reference genome. We identified 886 circRNAs, including numerous
      circular intronic RNAs and exonic circRNAs. Reverse transcription PCR (RT-PCR)
      and DNA sequencing analysis confirmed the presence of several circRNAs. Real-Time
      RT-PCR analysis exhibited resistance of sheep circRNAs to RNase R digestion. We
      found that many circRNAs interacted with muscle-specific miRNAs involved in
      growth and development of muscle, especially circ776. The GO and KEGG enrichment
      analysis showed that hosting genes of circRNAs was involved in muscle cell
      development and signaling pathway. CONCLUSION: The study provides comprehensive
      expression profiles of circRNAs in sheep skeletal muscle. Our study offers a
      large number of circRNAs to facilitate a better understanding of their roles in
      muscle growth. Meanwhile, we suggested that circ776 could be analyzed in future
      study.

PMID- 29642687
TI  - Estimation of genetic parameters for temperament in Jeju crossbred horses.
AB  - Objective: Temperament can be defined as a type of behavioral tendency that
      appears in a relatively stable manner in responses to various external stimuli
      over time. The aim of this study was to estimate genetic parameters for the
      records of temperament testing that are used to improve the temperament of Jeju
      crossbred (Jeju*Thoroughbred) horses. METHODS: This study was conducted using 205
      horses (101 females and 104 males) produced between 2010 and 2015. The
      experimental animals were imprinted and tamed according to the Manual for Horse
      Taming and Evaluation for Therapeutic Riding Horses and evaluated according to
      the categories for temperament testing (gentleness, patience, aggressiveness,
      sensitivity, and friendliness) between 15 months and 18 months of age. Each
      category was scored on a five-point linear scale. Genetic parameters for the test
      categories were analyzed using a multi-trait mixed model with repeated records.
      The ASReml program was used to analyze the data. RESULTS: The heritability of
      gentleness, patience, aggressiveness, sensitivity and friendliness ranged from
      0.08 to 0.53. The standard errors of estimated heritability ranged from 0.13 to
      0.17. The test categories showed high genetic correlations with each other,
      ranging from 0.96 to 0.99 and high repeatability, ranging from 0.70 to 0.73.
      CONCLUSION: The results of this study showed that the test categories had
      moderate heritability and high genetic correlations, but additional studies may
      be necessary to use the results for the improvement programs of the temperament
      of Jeju crossbred horses.

PMID- 29642689
TI  - The obesity paradox: the protective effect of obesity on right ventricular
      function using echocardiographic strain imaging in patients with pulmonary
      hypertension.
AB  - BACKGROUND: Obesity is associated with right ventricular (RV) dysfunction, but
      its effect on RV remodeling in patients with pulmonary hypertension (PHTN) has
      not been studied. We evaluated the effect of obesity, and its interplay with
      diabetes, in patients with PHTN using RV echocardiographic strain imaging.
      METHODS: One hundred eighty-five patients underwent echocardiographic imaging and
      pulmonary artery pressure was calculated using tricuspid regurgitation jet
      velocity. From focused RV apical-four-chamber view, global and mid peak systolic
      RV free wall longitudinal strain (FWLS) was calculated using speckle-tracking
      software. RESULTS: Global and mid RV FWLS in patients with PHTN (N.=84) was lower
      (-16.8+/-7 vs. 18.9+/-6.3, P=0.035 and -11.2+/-12.8 vs. -18.9+/-9.2, P=0.002
      respectively) compared with patients without PHTN (N.=101). Among patients
      without PHTN, obese patients (BMI>30) had lower global and mid RV FWLS (-17.2+/
      6.2 vs. -20.3+/-5.7, P=0.012 and -17.6+/-7.2 vs. -21.9+/-7.3, P=0.004), even
      after excluding diabetic patients (Mid RV FWLS -18.2+/-6.8 vs. -22.1+/-8,
      P=0.032). Among patients with PHTN, obese patients had similar RV FWLS compared
      with non-obese patients (P=0.46). However, on excluding diabetic patients from
      PHTN group, obese patients with PHTN had higher global and mid RV FWLS (-21.7+/
      5.7 vs. -16.1+/-8, P=0.017 and 23.8+/-4.8 vs. -17+/-9.4, P=0.009 respectively)
      compared to non-obese patients which suggests a protective effect of obesity on
      RV function in patients with PHTN. CONCLUSIONS: Obesity is associated with
      subclinical RV dysfunction as assessed by RV strain imaging, but paradoxically it
      may confer a protective effect on RV function once the patient develops PHTN.
      Future studies should evaluate the clinical impact of this paradox.

PMID- 29642690
TI  - Impella-protected PCI: the clinical results achieved so far.
AB  - The ability of interventional cardiologists to identify high-risk percutaneous
      coronary intervention (PCI) patients, requires the integration of different
      features belonging to medical history, organ damage, coronary anatomy and the
      nature of the acute event. The selection of a subgroup of patients that could
      benefit from mechanical support during interventions is a key feature to success.
      The introduction of the Impella percutaneous axial pump have added an easy-to-set
      up, less invasive and time-consuming active-support device to the interventional
      toolbox. Up to date, only few (four) randomized clinical trials (RCTs) have tried
      to address the clinical efficacy of Impella assistance for the treatment of this
      very high-risk population, but several large registries and multiple
      observational studies have demonstrated its safety, feasibility and hemodynamic
      performance. Although the largest RCT (PROTECT II) have been prematurely stopped
      due to the risk of futility despite the evidence of more complete
      revascularization in the Impella arm, the need for an adequate operator's
      learning curve must be considered. More recent insights suggest an effect of the
      device in optimizing end-organ perfusion and improving crucial parameters like
      renal function. Furthermore, available data suggest that vary early Impella
      support may improve patient's outcome in case of cardiogenic shock.

PMID- 29642688
TI  - Samter's Triad: State of the Art.
AB  - Samter's triad (ST) is a well-known disease characterized by the triad of
      bronchial asthma, nasal polyps, and aspirin intolerance. Over the past few years,
      a rapid development in the knowledge of the pathogenesis and clinical
      characteristics of ST has happened. The aim of this paper is to review the recent
      investigations on the pathophysiological mechanisms and genetic background,
      diagnosis, and different therapeutic options of ST to advance our understanding
      of the mechanism and the therapeutic control of ST. As concern for ST increase,
      more application of aspirin desensitization will be required to manage this
      disease successfully. There is also a need for continued research efforts in
      pathophysiology, treatment, and possible prevention.

PMID- 29642691
TI  - High-risk percutaneous coronary intervention: how to define it today?
AB  - Before the percutaneous era, the mortality rate of patients with coronary heart
      disease not suitable for cardiac surgery was extremely high. This limit has been
      progressively exceeded with the advent of minimally invasive approaches, which,
      although initially intended exclusively for low risk scenarios, was then employed
      in complex patients often too compromised to undergo cardiac surgery. We are
      currently witnessing, however, a sudden expansion in percutaneous coronary
      interventions (PCI) in extreme cases, perceived as high-risk by operators,
      imposing an important burden of human and economic resources on interventional
      cardiology as a whole. In this review, the literature regarding the current
      definition of high-risk PCI and its implications has been reviewed. In summary,
      all proposed definitions of high risk PCI combine features related to three main
      clinical areas: 1) patient risk factors and comorbidities (incorporating those
      which preclude surgical or percutaneous revascularization such as diabetes,
      chronic obstructive pulmonary disease, chronic kidney disease, lung disease,
      frailty, advanced age); 2) location of the disease and complexity of coronary
      anatomy (including multi-vessel disease, left main disease, chronic total
      occlusion, bifurcations); 3) hemodynamic clinical status (ventricular
      dysfunction, concomitant valvular disease or unstable characteristics).
      Importantly, encouraging results in terms of efficacy and gains in health status
      of PCI in (variously defined) high-risk, as compared to the low-risks patients,
      are reported. Thus, treating high-risk patients is becoming increasingly
      relevant, to the point that current guidelines now particularly highlight the
      appropriateness of percutaneous interventions in this setting .

PMID- 29642692
TI  - Non-cardiac chest pain: a 2018 update.
AB  - Non-cardiac chest pain (NCCP) is defined as recurring, angina-like, chest pain of
      non-cardiac origin. Studies have estimated that gastroesophageal reflux disease
      (GERD) is the most common contributing factor for NCCP. In patients with non-GERD
      related NCCP, esophageal motility disorders, and functional chest pain of
      presumed esophageal origin are the main underlying mechanisms for symptoms.
      Epidemiologic studies show a high prevalence of panic disorder, anxiety and major
      depression in NCCP patients. The diagnostic esophageal workup starts only after
      that cardiac and pulmonary diseases have been ruled out. NCCP patients with
      typical reflux symptoms are more likely to have GERD-related NCCP than those
      without typical reflux symptoms. High-dose proton pump inhibitor trial (PPI test)
      can be used to confirm the diagnosis of GERD-related NCCP. Negative upper
      endoscopy is quite common. For patients unresponsive to antireflux treatment and
      with negative endoscopy, impedance-pH monitoring should be done. Treatment of
      patients with non-GERD-related NCCP has focused on esophageal (hypercontractile
      or spastic) motility disorders and esophageal visceral hypersensitivity. In the
      first case, several trials using calcium channel blockers, nitrates,
      anticholinergics, or botulinum toxin injection and recent trials with endoscopic
      myotomy have been conducted. In case of visceral hypersensitivity, studies found
      that the amelioration, when compared to placebo, was significant with
      venlafaxine, sertraline, and imipramine. In this context, also cognitive
      behavioral therapy has been proposed.

PMID- 29642693
TI  - Tricuspid valve surgery: repair and replacement.
AB  - The tricuspid valve has historically received less attention than any other
      cardiac valve with regard to pathophysiology and surgical management. The
      tricuspid valve is part of a complex functional apparatus that includes the right
      atrium, right ventricle, and pulmonary circulation. Functional tricuspid
      regurgitation is the most common tricuspid valve disease and it occurs secondary
      to dilatation of tricuspid annulus and/or tethering of valve leaflets from right
      ventricular dilatation and dysfunction. However, recent expansion in the use of
      right-sided transvenous devices such as pacemakers and implantable defibrillators
      has been met with a parallel increase in the risk of organic tricuspid disease.
      Recent data suggest that tricuspid regurgitation is not benign, and many patients
      will benefit from intervention at the time of left-sided valve surgery, or early
      in isolated tricuspid valve disease. This review describes the various surgical
      options and strategies in the treatment of common tricuspid valve diseases.
      Current American and European guidelines advocate for a more proactive surgical
      approach in the treatment of tricuspid regurgitation and/or annular dilatation at
      the time of left-sided valve surgery. Tricuspid annuloplasty is the preferred
      technique given its superior long-term outcomes. This renewed interest in
      surgical repair has been ushered by the development of a newer generation of
      tricuspid annuloplasty rings, as well as technological strides in transcatheter
      therapies which now extend to include tricuspid pathologies in otherwise
      inoperable patients with advanced tricuspid disease and cardiomyopathy. Tricuspid
      disease is not a benign entity. An aggressive approach to surgical management as
      well as prophylactic interventions are becoming more widely adopted. Aggressive
      tricuspid surgery however, remains an area of controversy in cardiac surgery,
      although surgical repair remains the gold standard for functional tricuspid
      regurgitation with replacement reserved for advanced or organic tricuspid
      disease. Transcatheter therapy is primarily directed toward non-surgical patients
      and is not included in this review.

PMID- 29642694
TI  - Integrated quadruple stress echocardiography.
AB  - Stress Echocardiography (SE) is an established diagnostic technique. For 40
      years, the cornerstone of the technique has been the detection of regional wall
      motion abnormalities (RWMA), due to the underlying physiologically-relevant
      epicardial coronary artery stenosis. In the last decade, three new parameters
      (more objective than RWMA) have shown the potential to integrate and comple- ment
      RWMA: 1- B-lines, also known as ultrasound lung comets, as a marker of extra
      vascular lung water, measured using lung ultrasound with the 4-site simplified
      scan symmetrically of the antero- lateral thorax on the third intercostal space,
      from mid-axillary to anterior axillary and mid- clavicular line; 2-left
      ventricular contractile reserve (LVCR), assessed as the peak stress/rest ratio of
      left ventricular force, also known as elastance (systolic arterial pressure by
      cuff sphygmomanome- ter/end-systolic volume from 2D echocardiography); 3-
      coronary flow velocity reserve (CFVR) on left anterior descending coronary
      artery, calculated as peak stress/rest ratio of diastolic peak flow velocity
      assessed using pulsed-wave Doppler. The 4 parameters (RWMA, B-lines, LVCR and
      CFVR) now converge conceptually, logistically, and methodologically in the
      Integrated Quadruple (IQ)-SE. IQ-SE optimizes the versatility of SE to include in
      a one-stop shop the core "ABCD" (Asynergy+B-lines+Contractile reserve+Doppler
      flowmetry) protocol. It allows a synoptic assess- ment of parameters mirroring
      the epicardial artery stenosis (RWMA), interstitial lung water (B- lines),
      myocardial function (LVCR) and small coronary vessels (CFVR). Each variable has a
      clear clinical correlate, different and complementary to all others: RWMA
      identify an ischemic vs non- ischemic heart; B-lines a wet vs dry lung; LVCR a
      strong vs weak heart; CFVR a warm vs cold heart. IQ-SE is highly feasible, with
      minimal increase in the imaging and analysis time, and obvi- ous diagnostic and
      prognostic impact also beyond coronary artery disease - especially in heart fail-
      ure. Large scale effectiveness studies with IQ-SE are now under way with the
      Stress Echo 2020 study, and will provide the necessary evidence base prior to
      large scale acceptance of the tech- nique.

PMID- 29642695
TI  - Tricuspid valve imaging.
AB  - The right ventricle and tricuspid valve (TV) have long been neglected by
      cardiologists. Functional tricuspid regurgitation (TR) is nowadays the most
      common cause of severe TR and is emerging as a prognostic factor in many heart
      diseases. A multimodality imaging approach is fundamental for defining the
      pathophysiology of TR, using both two-dimensional and three-dimensional
      echocardiography, as well as CT scan. In particular, 3D echocardiography can
      characterize TV apparatus and tricuspid annulus; CT offers complementary
      information about annular structure, and its relationship with the right coronary
      artery. The following review will describe TV anatomy, define transthoracic and
      transesophageal echocardiographic views for evaluating TV morphology, function
      and TR grading with some clues on interventional perspectives.

PMID- 29642696
TI  - Periprocedural and perioperatory management of patients with tricuspid valve
      disease.
AB  - Tricuspid regurgitation (TR) is a common valvular lesion which may affect
      morbidity and mortality. It can be related to an intrinsic abnormality of the
      tricuspid valve leaflets (organic) or secondary to annular dilatation
      (functional). Often organic and functional TR coexist in the same patient. A long
      standing TR is associated with ascites, congestive hepatopathy, peripheral edema,
      renal failure, and abdominal fullness which significantly affect the outcome. In
      particular, the perioperative course may be complicated due to both the presence
      of comorbidities and the development of a severe postoperative right ventricle
      (RV) dysfunction. In fact, the TR may conceal a preoperative RV dysfunction due
      to a backflow in in the right atrium, which becomes overt only after the
      tricuspid valve (TV) repair/replacement (afterload mismatch). In light of this,
      an appropriate medical treatment before surgery may improve the performance of
      the RV, maximizing the result of the elective surgical therapy. The perioperative
      optimization should reduce the right atrial and ventricle overload, decrease the
      pulmonary vascular resistances, improve RV contractility and treat aggressively
      the arrhythmias. In doing so, the following rules should be considered: careful
      fluid administration, beta1-agonists favored over alpha-agonists to treat
      hemodynamic instability, and maintenance of a normal-to-elevated heart rate.
      Since the TV repair/replacement needs mechanical ventilation in both open and
      percutaneous surgery, a careful volume and pharmacological management should be
      adopted to counteract the detrimental effect of the mechanical ventilation on the
      top of an already dysfunctional RV. In fact, in the context of RV failure the
      cardiac output is strictly dependent on the preload and the increase of the
      intrathoracic pressure, reducing the venous return, may lead to acute heart
      failure. The intraoperative administration of volume and vasoactive drugs,
      titrated on the basis of the transesophageal echocardiography, permit to support
      the RV intraoperatively. Paracorporeal mechanical hemodynamic support should be
      always available as "bail out" in the event of intractable RV failure. In
      conclusion the patients undergoing TV surgery are complex and only a detailed
      anesthesiologic and surgical workup may decrease the perioperative mortality and
      morbidity.

PMID- 29642697
TI  - Bioaccumulation of Persistent Halogenated Organic Pollutants in Insects: Common
      Alterations to the Pollutant Pattern for Different Insects during Metamorphosis.
AB  - Few studies have examined the accumulation and fate of persistent halogenated
      organic pollutants (HOPs) in insects. We measured HOPs, including
      dichlorodiphenyltrichloroethanes (DDTs), polychlorinated biphenyls, and
      halogenated flame retardants, in insects from four taxonomic groups collected
      from an e-waste site. Dragonfly larvae collected from a pond contained the
      highest concentrations of all chemicals except DDTs, while the litchi stinkbugs
      contained the lowest. Different insect taxa exhibited different contaminant
      patterns which could be attributed to their habitats and feeding strategies.
      Bioaccumulation factors for dragonfly larvae and biomagnification factors for
      moth and grasshopper larvae were significantly positively correlated with the
      octanol-water partition coefficient of the chemicals (log KOW < 8). Common
      nonlinear correlations between the ratio of larval to adult concentrations and
      log KOW were observed for all taxa studied. The ratio of concentrations decreased
      with increasing values of log KOW (log KOW < 6-6.5), then increased (6 < log KOW
      < 8) and decreased again (log KOW > 8). This result implies that the mechanism
      that regulates organic pollutants in insects during metamorphosis is common to
      all the taxa studied.

PMID- 29642698
TI  - Single-Molecule Test for Markovianity of the Dynamics along a Reaction
      Coordinate.
AB  - In an effort to answer the much-debated question of whether the time evolution of
      common experimental observables can be described as one-dimensional diffusion in
      the potential of mean force, we propose a simple criterion that allows one to
      test whether the Markov assumption is applicable to a single-molecule trajectory
      x( t). This test does not involve fitting of the data to any presupposed model
      and can be applied to experimental data with relatively low temporal resolution.

PMID- 29642699
TI  - Measuring Interfacial Tension of Emulsions in Situ by Microfluidics.
AB  - Interfacial tension is a key parameter affecting industrially relevant properties
      of emulsions, such as morphology and stability. Although several methods are
      available to measure interfacial tension, they are based on generation of
      droplets starting from separate emulsion components and cannot directly probe the
      interfacial tension of an emulsion as such. Here, a novel microfluidic
      tensiometry device to measure interfacial tension of a water-in-oil emulsion in
      situ as a function of surfactant concentration is presented. In our approach,
      interfacial tension is obtained from a quantitative analysis of the deformation
      of individual emulsion droplets under steady state shear flow in microfluidic
      channels. The technique is validated by comparing the results with experimental
      data obtained by the pendant drop method in a broad range of interfacial tension
      values. A very good agreement is found, and an estimate of the surfactant
      critical micellar concentration (CMC) is also obtained. The proposed microfluidic
      setup can be used even at high surfactant concentrations, where the measurement
      is made more challenging by sample viscoelasticity, thus providing a powerful
      tool to determine the interfacial tension of complex systems in an extended
      concentration range. The technique could be also used for in-line monitoring of
      emulsion processing.

PMID- 29642700
TI  - Pressure-Induced Topological Phase Transitions in CdGeSb2 and CdSnSb2.
AB  - Using first-principles calculations, we study the occurrence of topological
      quantum phase transitions (TQPTs) as a function of hydrostatic pressure in
      CdGeSb2 and CdSnSb2 chalcopyrites. At ambient pressure, both materials are
      topological insulators, having a finite band gap with inverted order of Sb-s and
      Sb-p x,p y orbitals of valence bands at the Gamma point. Under hydrostatic
      pressure, the band gap reduces, and at the critical point of the phase
      transition, these materials turn into Dirac semimetals. Upon further increasing
      the pressure beyond the critical point, the band inversion is reverted, making
      them trivial insulators. This transition is also captured by the Luttinger model
      Hamiltonian, which demonstrates the critical role played by pressure-induced
      anisotropy in frontier bands in driving the phase transitions. These theoretical
      findings of peculiar coexistence of multiple topological phases provide a
      realistic and promising platform for experimental realization of the TQPTs.

PMID- 29642701
TI  - Critical Role of Water in Defect Aggregation and Chemical Degradation of
      Perovskite Solar Cells.
AB  - The chemical stability of methylammonium lead iodide (MAPbI3) under humid
      conditions remains the primary challenge facing halide perovskite solar cells. We
      investigate defect processes in the water-intercalated iodide perovskite
      (MAPbI3_H2O) and monohydrated phase (MAPbI3.H2O) within a first-principles
      thermodynamic framework. We consider the formation energies of isolated and
      aggregated vacancy defects with different charge states under I-rich and I-poor
      conditions. It is found that a PbI2 (partial Schottky) vacancy complex can be
      formed readily, while the MAI vacancy complex is difficult to form in the hydrous
      compounds. Vacancies in the hydrous phases create deep charge transition levels,
      indicating the degradation of the lead halide perovskite upon exposure to
      moisture. Electronic structure analysis supports a mechanism of water-mediated
      vacancy pair formation.

PMID- 29642702
TI  - G-Quadruplex DNA with an Apurinic Site as a Soft Molecularly Imprinted Sensing
      Platform.
AB  - Molecularly imprinted polymers (MIPs) provide versatile sensor platforms to
      recognize targets by shape complementarity. However, the rigid structure of the
      classic MIPs compromises the signal transduction with necessary polymer and
      target modifications. Herein, we tried to use a flexible DNA that has a perfectly
      structured folding as the soft molecularly imprinted polymer (SMIP) for a
      straightforward sensor. As a proof of concept, the guanosine SMIP recognition was
      achieved by removal of a guanosine from a G-quadruplex-forming sequence (G4). The
      G4 folding structure with such an apurinic site (AP site) provides a well-defined
      MIP binding accommodation for guanosine according to the shape complementarity.
      The guanosine binding at the AP site subsequently leads to a conformation change
      suitable for remote readout using a G4-specific fluorescent ligand. The G4
      sequence and AP site position were optimized for this SMIP behavior. Due to the
      G4 compact structure and the remaining hydrogen bonding pattern, nucleosides
      other than guanosine and negatively charged nucleotides exhibit no binding with
      the AP site, suggesting a high selectivity in the SMIP recognition. The proposed
      rationale was then convinced by the alkaline phosphatase-catalyzed GMP
      hydrolysis. Our work will inspire more interest in exploring nucleic acids as the
      SMIP frameworks due to their variant conformations and well-established molecular
      engineering.

PMID- 29642703
TI  - Hydrogen Bond-Regulated Boron Nitride Network Structures for Improved Thermal
      Conductive Property of Polyamide-imide Composites.
AB  - Highly thermal conductive polymer composites with minimized content of fillers
      are desirable for handling the issue in thermal management in modern electronics.
      However, the difficulty of filler dispersion restricts the heat dissipation
      performance of thermoplastic composites and the intermolecular interaction is
      another crucial factor in this problem. In the present study, the hydrogen bond
      was used to regulate the formation of the three-dimensional boron nitride (3D BN)
      interconnected network to act as a high thermal conductive network in
      thermoplastic polyamide-imide (PAI) materials. The prepared electrical insulated
      PAI/3D-BN composites have a thermal conductivity (TC) of 1.17 W.m-1.K-1 at a low
      BN loading of 4 wt %/2 vol % and exhibit a thermal conductivity enhancement of
      409%. We attribute the increased TC to the construction of 3D BN interconnected
      network and the hydrogen bond regulated between hydroxylated BN and polyvinyl
      alcohol, in which an effective thermal conductive network is constructed. This
      study provides a guided hydrogen bond strategy for thermally conductive polymer
      composites with good mechanical and electrical insulation properties in thermal
      management and other applications.

PMID- 29642704
TI  - Selective, Scalable Synthesis of C60-Fullerene/Indene Monoadducts Using a
      Microwave Flow Applicator.
AB  - The synergy of continuous processing and microwave heating technologies has
      unlocked scalable (g/h), safe and efficient reaction conditions for synthesis of
      fullerene/indene-based organic photovoltaic acceptor materials in a
      nonchlorinated solvent with levels of productivity unparalleled by previous
      syntheses. The microwave flow reactor sustains high temperature while employing
      short residence times, reaction conditions which uniquely allow the selective
      synthesis of fullerene/indene monoadducts. Design of experiments analysis
      revealed residence time as the most crucial factor for conversion and selectivity
      control.

PMID- 29642705
TI  - Durian-Shaped CdS@ZnSe Core@Mesoporous-Shell Nanoparticles for Enhanced and
      Sustainable Photocatalytic Hydrogen Evolution.
AB  - In artificial photosynthesis, the establishment of design guidelines for
      nanostructures to maximize the photocatalytic performance remains a great
      challenge. In contrast with the intense research into band-offset tuning for
      photocatalysts, the relationship between nanostructures and photoinduced carrier
      dynamics has still been insufficiently explored. We synthesized durian-shaped
      CdS@ZnSe core@mesporous-shell nanoparticles ( d-CdS/ZnSe NPs) and investigated
      the carrier dynamics in photocatalytic hydrogen evolution. The cocatalyst-free d
      CdS/ZnSe NPs exhibited high photocatalytic activity for H2 evolution (14.8%
      apparent quantum yield at 420 nm) and excellent stability (maintaining 80%
      activity after 72 h) under visible-light irradiation (>422 nm). The transient
      absorption measurement and flash photolysis time-resolved microwave conductivity
      unveiled that the ultra-long-lived charge separation (>6.2 ms) and swift hole
      transfer to the surfaces of ZnSe shell (11 ns) contribute the high catalytic
      activity and stability. The present work provides a novel insight into designing
      nanoparticulate photocatalysts with optimized performance.

PMID- 29642706
TI  - What Is Neglect? State Legal Definitions in the United States.
AB  - Neglect is the most common form of reported child maltreatment in the United
      States with 75.3% of confirmed child maltreatment victims in 2015 neglected.
      Despite constituting the majority of reported child maltreatment cases and
      victims, neglect still lacks a standard definition. In the United States,
      congruent with the pervasiveness of law in child welfare systems, every state and
      the District of Columbia has its own statutory definition of neglect. This study
      used content analysis to compare state legal statutory definitions with the
      Fourth National Incidence Survey (NIS-4) operationalization of neglect. The
      resulting data set was then analyzed using cluster analysis, resulting in the
      identification of three distinct groups of states based on how they define
      neglect: minimal, cornerstones, and expanded. The states' definitions incorporate
      few of the NIS-4 components. Practice and policy implications of these
      constructions of neglect definitions are discussed.

PMID- 29642707
TI  - An integrated motivational interviewing and cognitive-behavioural intervention
      promoting physical activity maintenance for adults with chronic health
      conditions: A feasibility study.
AB  - Objectives Physical activity is recommended for managing chronic health
      conditions but is rarely maintained. This feasibility study aimed to evaluate the
      preliminary efficacy of a motivational interviewing and cognitive-behavioural
      intervention for long-term physical activity for adults with chronic health
      conditions. Methods Participants ( N = 37) with stable conditions (e.g. diabetes)
      were randomized into a three-month motivational interviewing and cognitive
      behavioural group ( N = 20) or usual care ( N = 17) after completing a physical
      activity referral scheme. Participants completed physical activity (e.g. average
      steps per day and kilocalorie expenditure), psychological (e.g. self-efficacy)
      and epidemiological (e.g. body mass index) standardized measures at baseline,
      three- and six-month follow-up. Treatment fidelity and feasibility were assessed.
      Results Thirty-five participants completed the study (96% retention). The
      motivational interviewing and cognitive-behavioural group maintained kilocalorie
      expenditure at three ( p = 0.009) and six months ( p = 0.009). Exercise barrier
      self-efficacy ( p = 0.03), physical ( p = 0.02) and psychological ( p = 0.01)
      physical activity experiences were increased at three months only. No difference
      was found for average steps/day, social support, coping skills and
      epidemiological factors. Discussion This is the first study to demonstrate the
      feasibility and preliminary efficacy of motivational interviewing and cognitive
      behavioural interventions for promoting physical activity maintenance in a
      clinical population. A large-scale trial with a longer follow-up (>=6 months) is
      warranted with treatment fidelity assessment.

PMID- 29642708
TI  - Coronary Artery Development: Origin, Malformations, and Translational Vascular
      Reparative Therapy.
AB  - After thickening of the cardiac chamber walls during embryogenesis, oxygen and
      nutrients can no longer be adequately supplied to cardiac cells via passive
      diffusion; therefore, a primitive vascular network develops to supply these vital
      structures. This plexus further matures into coronary arteries and veins, which
      ensures continued development of the heart. Various models have been proposed to
      account for the growth of the coronary arteries. However, lineage-tracing studies
      in the last decade have identified 3 major sources, namely, the proepicardium,
      the sinus venosus, and endocardium. Although the exact contribution of each
      source remains unknown, the emerging model depicts alternative pathways and
      progenitor cells, which ensure successful coronary angiogenesis. We aim to
      explore the current trends in coronary artery development, the cellular and
      molecular signals regulating heart vascularization, and its implications for
      heart disease and vascular regeneration.

PMID- 29642709
TI  - Thromboembolism and Mortality in the Tasmanian Atrial Fibrillation Study.
AB  - BACKGROUND: Although utilization of anticoagulation in patients with atrial
      fibrillation (AF) has increased in recent years, contemporary data regarding
      thromboembolism and mortality incidence rates are limited outside of clinical
      trials. This study aimed to investigate the impact of the direct oral
      anticoagulants (DOACs) on the clinical outcomes of patients with AF included in
      the Tasmanian Atrial Fibrillation Study. METHODS: The medical records of all
      patients with a primary or secondary diagnosis of AF who presented to public
      hospitals in Tasmania, Australia, between 2011 and 2015, were retrospectively
      reviewed. We investigated overall thromboembolic events (TEs), ischemic
      stroke/transient ischemic attack (IS/TIA), and mortality incidence rates in
      patients admitted to the Royal Hobart Hospital, the main teaching hospital in the
      state. We compared outcomes in 2 time periods: prior to the availability of DOACs
      (pre-DOAC; 2011 to mid-2013) and following their general availability after
      government subsidization (post-DOAC; mid-2013 to 2015). RESULTS: Of the 2390
      patients with AF admitted during the overall study period, 942 patients newly
      prescribed an antithrombotic medication (465 and 477 from the pre-DOAC and post
      DOAC time periods, respectively) were followed. We observed a significant
      decrease in the incidence rates of overall TE (3.2 vs 1.7 per 100 patient-years
      [PY]; P < .001) and IS/TIA (2.1 vs 1.3 per 100 PY; P = .022) in the post-DOAC
      compared to the pre-DOAC period. All-cause mortality was significantly lower in
      the post-DOAC period (2.9 vs 2.2 per 100 PY, P = .028). Increasing age, prior
      stroke, and admission in the pre-DOAC era were all risk factors for TE, IS/TIA,
      and mortality in this study population. The risk of IS/TIA was more than doubled
      (hazard ratio: 2.54; 95% confidence interval: 1.17-5.52) in current smokers
      compared to ex- and nonsmokers. CONCLUSION: Thromboembolic event and all-cause
      mortality rates were lower following the widespread availability of DOACs in this
      population.

PMID- 29642710
TI  - Teaching Residents How to Talk About Death and Dying: A Mixed-Methods Analysis of
      Barriers and Randomized Educational Intervention.
AB  - OBJECTIVES: We present a pilot study exploring the effects of a brief, 30-minute
      educational intervention targeting resident communication surrounding dying in
      the intensive care unit (ICU). We sought to determine whether simulation or
      didactic educational interventions improved resident-reported comfort,
      preparation, and skill acquisition. We also sought to identify resident barriers
      to using the word "dying." METHODS: In this mixed-methods prospective study,
      second- and third-year medical residents were randomized to participate in a
      simulation-based communication training or a didactic session. Residents
      completed a pre-post survey after the sessions evaluating the sessions and
      reflecting on their use of the word "dying" in family meetings. RESULTS: Forty
      five residents participated in the study. Residents reported increases in comfort
      (Mean [M]-pre = 3.3 [standard deviation: 0.6], M-post = 3.7 [0.7]; P < .01, Cohen
      d = 0.75) and preparation (M-pre = 3.4 [0.7], M-post = 3.9 [0.6]; P < .01, d =
      1.07) using the word "dying" after both the simulation and didactic versions.
      Residents randomized to the simulation reported they were more likely to have
      learned new skills as compared to residents in the didactic (M-simulation = 2.2
      [0.4], M-didactic = 1.9 [0.3]; P = .015, d = 0.80). They estimated that they used
      the word "dying" in 50% of their end-of-life (EOL) conversations and identified
      uncertain prognosis as the main barrier to explicitly stating the word "dying."
      CONCLUSION: A 30-minute educational intervention improves internal medicine
      residents' self-reported comfort and preparation in talking about death and dying
      in the ICU. Residents in simulation-based training were more likely to report
      they learned new skills as compared to the didactic session. Residents report
      multiple barriers to using the word "dying" EOL conversations.

PMID- 29642711
TI  - Recent advances in inhibitors of sirtuin1/2: an update and perspective.
AB  - Sirtuins (SIRT) are coenzyme NAD+-dependent histone deacetylases for the transfer
      of modified acetyl groups. Sirtuins are widely involved in various physiological
      processes and therefore associated with cardiovascular disease, diabetes,
      Parkinson's disease, cancer and beyond. Consequently, the development of
      modulators for  sirtuins has considerable clinical value. To date, a variety of
      SIRT1/2 inhibitors have been reported and none has been approved for the market.
      This review summarizes the recent progress in the discovery and development of
      SIRT1/2 inhibitors including their inhibitory potency, structure-activity
      relationship and binding mode analysis as well as discusses the perspective for
      the future development of SIRT1/2 inhibitors.

PMID- 29642712
TI  - Methodological advances, opportunities, and challenges in AAC research.
AB  - Since its inception in 1985, the AAC journal has been publishing scientific
      articles related to the field of augmentative and alternative communication (AAC)
      that (a) report research concerning assessment, treatment, rehabilitation, and
      education of people who use or have the potential to use AAC systems and (b)
      cover theory, technology, and systems development relevant to AAC. The journal
      has maintained a consistent focus on the science and practice of AAC while also
      advancing in varied and impressive ways. Among the many developments apparent in
      AAC over the years, methodological advancements emerge as pivotal within the
      evolution of the science of AAC. This report examines the state of the science in
      behavioral AAC research with specific regard to changes and opportunities in
      research methodology. Illustrations from articles published in Volume 1 (1985)
      and Volume 32 (2016) of AAC are used in this paper to frame commentary on (a)
      contextual consideration in conducting AAC research, (b) types of research
      design, (c) considerations of procedural rigor, and (d) future methodological
      directions and resources. If the AAC field is to meet the goal of ensuring that
      all individuals with complex communication needs achieve their full potential,
      meaningful questions must be posed to address key problems, and rigorous
      scientific methods must be employed to answer these questions.

PMID- 29642713
TI  - House Dust Mite Sublingual Immunotherapy for Pediatric Patients With Allergic
      Asthma.
AB  - OBJECTIVE: To review the published literature evaluating administration of house
      dust mite (HDM) sublingual immunotherapy (SLIT) in pediatric patients with
      allergic asthma. DATA SOURCES: PubMed database search (1966 to November 2017)
      using the search terms allergy, allergic rhinitis, asthma, allergic asthma, house
      dust mite, allergen immunotherapy, subcutaneous immunotherapy, sublingual
      immunotherapy, MK-8237, children, and pediatric. Package labeling and references
      from identified articles were also reviewed. STUDY SELECTION AND DATA EXTRACTION:
      Studies published in English evaluating the efficacy of HDM SLIT in children <18
      years of age were included. DATA SYNTHESIS: Patients with allergic asthma who
      fail to improve with pharmacotherapy may require disease-modifying, HDM-specific
      immunotherapy. Acceptance of subcutaneous immunotherapy (SCIT) in the pediatric
      population is limited by the need for weekly injections and the risk of systemic
      adverse effects. Trials in pediatric patients with allergic rhinitis and asthma
      monosensitized to HDM demonstrated mixed results, likely because of variability
      in methodologies. SLIT reduced asthma symptoms in 8 placebo-controlled studies;
      however, asthma medication use was reduced in just 4 trials. Compared with
      pharmacotherapy alone, SLIT and SCIT decreased asthma symptom scores similarly
      for up to 3 years. Sequential SCIT/SLIT decreased both asthma symptoms and
      medication scores and was more effective than SLIT alone. CONCLUSIONS: Sublingual
      HDM immunotherapy reduces symptom scores in pediatric patients with allergic
      asthma but may be slower in onset and less effective than SCIT in reducing asthma
      medication use.

PMID- 29642714
TI  - Study of the Determinants of Chronic Malnutrition in Northern Nigeria:
      Quantitative Evidence from the Nigeria Demographic and Health Surveys
      International Food Policy Research Institute (IFPRI) Working Paper 45 (September
      2017).
AB  - BACKGROUND: Close to half of all children younger than 5 years in the Northeast
      and Northwest geopolitical zones were estimated to be stunted in their growth for
      their age in 2013 compared to 22% of children in the rest of Nigeria. OBJECTIVES:
      We examine the drivers of chronic child undernutrition in northern Nigeria and
      how those drivers differ from other areas of the country. METHODS: Both a
      standard child-level regression-based approach and decomposition analysis were
      used to address the determinants of stunting and decompose how drivers differ
      between northern Nigeria and other areas of the country using 2008 and 2013
      Nigeria DHS data. RESULTS: There are strong differences in the levels of the
      determinants of undernutrition in young children between the 2 parts of the
      country. However, equally important, the decomposition analysis shows that there
      are significant differences between northern Nigeria and other areas of Nigeria
      in the effect of the same determinant of nutritional status in accelerating or
      retarding the linear growth of young children. CONCLUSIONS: A national program to
      address child undernutrition must recognize this heterogeneity in its design. To
      impose across Nigeria, a single set of approaches to address the factors which
      results in stunted children is likely to fail for large numbers of children if
      these strong geographical differences in how these determinants operate to affect
      child nutritional status are not considered. Solutions need to be developed
      within northern Nigeria to more closely reflect the way the determinants of
      nutritional status operate in this area of the country.

PMID- 29642715
TI  - Effects of dynamic text in an AAC app on sight word reading for individuals with
      autism spectrum disorder.
AB  - The purpose of this study was to investigate the effects of Transition to
      Literacy (T2L) software features (i.e., dynamic text and speech output upon
      selection of a graphic symbol) within a grid display in an augmentative and
      alternative communication (AAC) app, on the sight word reading skills of
      individuals with autism spectrum disorders (ASD) and complex communication needs.
      The study implemented a single-subject multiple probe research design across one
      set of three participants. The same design was utilized with an additional set of
      two participants. As part of the intervention, the participants were exposed to
      an AAC app with the T2L features during a highly structured matching task. With
      only limited exposure to the features, the five participants all demonstrated
      increased accuracy of identification of 12 targeted sight words. This study
      provides preliminary evidence that redesigning AAC apps to include the provision
      of dynamic text combined with speech output, can positively impact the sight-word
      reading of participants during a structured task. This adaptation in AAC system
      design could be used to complement literacy instruction and to potentially infuse
      components of literacy learning into daily communication.

PMID- 29642716
TI  - Thematic analysis of blog narratives written by people with Alzheimer's disease
      and other dementias and care partners.
AB  - Limited research takes a socio-biographical approach to study the experiences and
      perspectives of individuals affected by Alzheimer's disease and related
      dementias. The purpose of this study was to thematically analyze blog narratives
      written by people with Alzheimer's disease and related dementia and care partners
      in order to increase understanding of their experiences. Nineteen blogs written
      by people with Alzheimer's disease and related dementia and 44 blogs written by
      care partners were analyzed. The first two authors utilized line-by-line open
      coding to analyze five posts from each group for the development of a codebook.
      Using NVivo software, the first author proceeded to code the remaining blogs for
      emergent themes and subcategories. Emergent themes included (1) effects of
      Alzheimer's disease and related dementia on the person with Alzheimer's disease
      and related dementia and/or the care partner; (2) seeing the positives; (3)
      feeling out of control; (4) advocacy and empowerment; (5) coping mechanisms and
      compensatory strategies; and (6) candid descriptions of experiences with
      Alzheimer's disease and related dementia. These themes also encompassed numerous
      subcategories that are discussed in this paper. Results from this study provide
      insights into the experiences of individuals affected by Alzheimer's disease and
      related dementia. Writers discussed several topics that are consistent with
      research on illness narratives of individuals with chronic diseases, including
      loss of identity, strategies for coping, and poignant descriptions of life with
      the disease. This study provides information in the form of overlapping themes
      from first-person perspectives of numerous individuals affected by Alzheimer's
      disease and related dementia. This type of data is crucial to understand the
      experiences of people who live with ADRD.

PMID- 29642717
TI  - Optimizing Prediction Using Bayesian Model Averaging: Examples Using Large-Scale
      Educational Assessments.
AB  - This article provides a review of Bayesian model averaging as a means of
      optimizing the predictive performance of common statistical models applied to
      large-scale educational assessments. The Bayesian framework recognizes that in
      addition to parameter uncertainty, there is uncertainty in the choice of models
      themselves. A Bayesian approach to addressing the problem of model uncertainty is
      the method of Bayesian model averaging. Bayesian model averaging searches the
      space of possible models for a set of submodels that satisfy certain scientific
      principles and then averages the coefficients across these submodels weighted by
      each model's posterior model probability (PMP). Using the weighted coefficients
      for prediction has been shown to yield optimal predictive performance according
      to certain scoring rules. We demonstrate the utility of Bayesian model averaging
      for prediction in education research with three examples: Bayesian regression
      analysis, Bayesian logistic regression, and a recently developed approach for
      Bayesian structural equation modeling. In each case, the model-averaged estimates
      are shown to yield better prediction of the outcome of interest than any submodel
      based on predictive coverage and the log-score rule. Implications for the design
      of large-scale assessments when the goal is optimal prediction in a policy
      context are discussed.

PMID- 29642718
TI  - Psychotropic Pharmacotherapy Associated With QT Prolongation Among Veterans With
      Posttraumatic Stress Disorder.
AB  - BACKGROUND: In 2012, the Food and Drug Administration issued Drug Safety
      Communications on several drugs associated with QT prolongation and fatal
      ventricular arrhythmias. Among these was citalopram, a selective serotonin
      reuptake inhibitor (SSRI) approved for depression and commonly used for
      posttraumatic stress disorder (PTSD). Evaluation of the risk for QT prolongation
      among other psychotropic drugs for individuals with PTSD remains limited.
      OBJECTIVE: Explore psychotropic drugs associated with QT prolongation among
      veterans with PTSD. METHODS: Patients in the Veterans Health Administration in
      2006-2009 with PTSD and QT prolongation (176 cases) were matched 1:4 on age,
      gender, visit date and setting, and physical comorbidity. Classification trees
      assessed QT prolongation risk among prescribed medications (n=880). RESULTS:
      Receipt of any drug with known risk of QT prolongation varied by group (23% QT
      cases vs 15% control, p<0.01). Psychotropic medications conferring significant
      risks included ziprasidone (3% vs 1%, p=0.02) and buspirone (6% vs 2%, p=0.01).
      Increased risk was not observed for the SSRIs, citalopram and fluoxetine.
      Classification trees found that sotalol and amitriptyline carried greater risk
      among cardiac patients and methadone, especially if prescribed with quetiapine,
      among noncardiac patients. Per adjusted survival model, patients with QT
      prolongation were at increased risk for death (hazard ratio=1.60; 95% CI=1.04
      2.44). CONCLUSIONS: Decision models are particularly advantageous when exploring
      nonlinear relationships or nonadditive interactions. These findings may
      potentially affect clinical decision-making concerning treatment for PTSD. For
      patients at higher risk of QT prolongation, antidepressants other than
      amitriptyline should be considered. Medications for comorbid conditions should
      also be closely monitored for heightened QT prolongation risk.

PMID- 29642719
TI  - Impact of Pharmacist-Physician Collaboration on Osteoporosis Treatment Rates.
AB  - BACKGROUND: The vast majority of women at high risk for osteoporotic fractures
      are not treated, despite known significant clinical and economic consequences of
      this prevalent condition. To date, this is the first study of this size and
      duration to examine the role of pharmacists in management of osteoporosis in a
      family medicine clinic. OBJECTIVE: To compare the initiation or continuation of
      prescription antifracture therapy in high-risk patients with collaborative
      pharmacist-physician to physician-only management; secondarily, to evaluate
      recommendation rates for antifracture therapy and calcium and vitamin D. METHODS:
      This retrospective cohort analysis included women older than 65 years with a dual
      energy X-ray absorptiometry (DXA) scan ordered by a family medicine physician.
      High risk was defined as T-scores <=-2.5 at the lumbar spine, femoral neck, or
      33% radius, or a FRAX 10-year fracture risk score >=20% for major osteoporosis
      related or >=3% for hip fractures. RESULTS: There were 466 (311 high-risk)
      pharmacist-physician and 549 (237 high-risk) physician-managed DXAs included. For
      high-risk DXAs, collaborative management resulted in increased rates of receiving
      antifracture therapy prescriptions over physician-only management (66% vs 34%, P
      < 0.001), advisement for antifracture therapy (87% vs 32%, P < 0.001), and
      calcium and vitamin D (97% vs 45%, P < 0.001). Collaborative management also
      improved calcium and vitamin D advisement among all DXAs (96% vs 46%, P < 0.01).
      There was no difference in adverse events documented in the pharmacist-physician
      compared with physician-only management (7.2% vs 3.7%, P = 0.32). Conclusion and
      Relevance: Pharmacist-physician collaboration is associated with higher treatment
      rates of osteoporosis. This study supports the pharmacist-physician partnership
      as one method of improving osteoporosis management.

PMID- 29642720
TI  - Use of Potentially Inappropriate Medications in People With Dementia in Vietnam
      and Its Associated Factors.
AB  - This study examined the use of potentially inappropriate medicines that may
      affect cognition (PIMcog) in people with dementia and its associated factors.
      Medical records of all outpatients with dementia attending a tertiary hospital in
      Vietnam between January 1, 2015, and December 31, 2016, were examined. Medicine
      use was assessed against a list of PIMcog. Variables associated with having a
      PIMcog were assessed using a multiple logistic regression. Of the 128 patients,
      41% used a PIMcog, 39.1% used cholinesterase inhibitors (CEIs) concomitantly with
      anticholinergics, and 18% used antipsychotics. The number of hospital visits
      (adjusted odds ratio [OR]: 1.08; 95% confidence interval [CI]: 1.02-1.16) and
      number of treating specialists (adjusted OR: 0.61; 95% CI: 0.45-0.83) were
      associated with PIMcog use. This study highlights a high-level use of medicines
      that can further impair cognition or reduce the effectiveness of CEIs in people
      with dementia. Efforts to improve quality use of medicines for this population
      are warranted.

PMID- 29642721
TI  - Placing your faith on the betting floor: Religiosity predicts disordered gambling
      via gambling fallacies.
AB  - Background and aims We examined the potential role religious beliefs may play in
      disordered gambling. Specifically, we tested the idea that religiosity primes
      people to place their faith in good fortune or a higher power. In the context of
      gambling, however, this may lead to gambling fallacies (e.g., erroneous beliefs
      that one has control over a random outcome). People who are high in religiosity
      may be more at risk of developing gambling fallacies, as they may believe that a
      higher power can influence a game of chance. Thus, this research investigated the
      relationship between religiosity and gambling problems and whether gambling
      fallacies mediated this relationship. Methods In Study 1, we recruited an online
      sample from Amazon's Mechanical Turk to complete measures that assessed the
      central constructs (religiosity, disordered gambling, and gambling fallacies). In
      Study 2, we conducted a secondary analysis of a large data set of representative
      adults (N = 4,121) from a Canadian province, which contained measures that
      assessed the constructs of interest. Results In Study 1, religiosity
      significantly predicted gambling problem. Conversely, there was no direct
      relationship between religiosity and gambling in Study 2. Importantly, a
      significant indirect effect of religiosity on disordered gambling severity
      through gambling fallacies was found in both studies, thus establishing
      mediation. The results remained the same when controlling for age, gender,
      ethnicity, and socioeconomic status for both studies. Discussion and conclusion
      These findings suggest religiosity and its propensity to be associated with
      gambling fallacies, which should be considered in the progression (and possibly
      treatment) of gambling.

PMID- 29642722
TI  - The personality, motivational, and need-based background of problematic Tinder
      use.
AB  - Background and aims Tinder is a geo-located online dating application, which is
      present in almost 200 countries and has 10 million daily users. The aim of the
      present research was to investigate the motivational, personality, and basic
      psychological need-related background of problematic Tinder use. Methods After
      qualitative pretest and item construction, in Study 1 (N = 414), confirmatory
      factor analysis was conducted to corroborate the different motivational factors
      behind Tinder use. In Study 2 (N = 346), the associations between Big Five
      traits, Tinder motivations, and problematic Tinder use were examined with
      structural equation modeling (SEM). In Study 3 (N = 298), the potential role of
      general self-esteem, relatedness need satisfaction, and frustration in relation
      to Tinder-use motivations and problematic Tinder use was examined with SEM.
      Results In Study 1, a 16-item first-order factor structure was identified with
      four motivational factors, such as sex, love, self-esteem enhancement, and
      boredom. In Study 2, problematic Tinder use was mainly related to using Tinder
      for self-esteem enhancement. The Big Five personality factors were only weakly
      related to the four motivations and to problematic Tinder use.
      Counterintuitively, Study 3 showed that instead of global self-esteem,
      relatedness need frustration was the strongest predictor of self-esteem
      enhancement Tinder-use motivation which, in turn, was the strongest predictor of
      problematic Tinder use. Discussion Four motivational factors were identified as
      predictors of problematic use with need frustration being a relevant background
      variable instead of general personality traits.

PMID- 29642724
TI  - Foley catheter with simultaneous oxytocin on labor induction: a meta-analysis of
      randomized controlled trials.
AB  - OBJECTIVE: It is unclear that whether Foley catheter with simultaneous oxytocin
      could improve the efficacy of induction outcome. METHOD: To conduct a meta
      analysis of randomized controlled trial (RCT) studies to evaluate the effect of
      Foley catheter with simultaneous oxytocin on labor induction. PubMed, Embase, and
      other databases were searched from their inception to July 2017. We included all
      RCTs comparing Foley catheter with simultaneous oxytocin (i.e. intervention
      group) with Foley catheter followed by oxytocin (i.e. control group) in the three
      kinds of women (nulliparas and multiparas/only nulliparas/only multiparas). We
      estimate summarized relative risk (RR) and 95% confidence intervals (CIs) for
      dichotomous outcomes, standard mean difference for continuous outcomes. Fixed-
      and random-effects models were used, depending on heterogeneity. RESULTS: After
      application of our inclusion and exclusion criteria, six RCTs with a total of
      1133 participants were identified. We found that only nulliparas had significant
      RR of delivery within 24 h (RR = 1.32, 95% CI: 1.12, 1.55, I2 = 46.5%).
      Meanwhile, there was no statistically significant difference between intervention
      and control groups in vaginal delivery in 24 h, cesarean delivery, time to
      delivery, and Apgar score at 5 min less than 7. Foley catheter with simultaneous
      oxytocin did not increase the risk of side effects, included chorioamnionitis,
      postpartum hemorrhage, uterine hyperstimulation, and neonatal intensive care unit
      admission. CONCLUSION: The results seem to support the use of oxytocin to a Foley
      catheter at the initiation of labor induction, as it might lead to increases the
      rate of delivery within 24 h in nulliparas.

PMID- 29642723
TI  - Impulsivity traits and addiction-related behaviors in youth.
AB  - Background and aims Impulsivity is a risk factor for addictive behaviors. The
      UPPS-P impulsivity model has been associated with substance addiction and
      gambling disorder, but its role in other non-substance addiction-related
      behaviors is less understood. We sought to examine associations between UPPS-P
      impulsivity traits and indicators of multiple substance and non-substance
      addiction-related behaviors in youth with varying involvement in these behaviors.
      Methods Participants (N = 109, aged 16-26 years, 69% males) were selected from a
      national survey based on their level of externalizing problems to achieve a broad
      distribution of involvement in addiction-related behaviors. Participants
      completed the UPPS-P Questionnaire and standardized questionnaires assessing
      problematic use of substances (alcohol, cannabis, and other drugs) and non
      substances (Internet gaming, pornography, and food). Regression analyses were
      used to assess associations between impulsivity traits and indicators of
      addiction-related behaviors. Results The UPPS-P model was positively associated
      with indicators of all addiction-related behaviors except problematic Internet
      gaming. In the fully adjusted models, sensation seeking and lack of perseverance
      were associated with problematic use of alcohol, urgency was associated with
      problematic use of cannabis, and lack of perseverance was associated with
      problematic use of other drugs than cannabis. Furthermore, urgency and lack of
      perseverance were associated with binge eating and lack of perseverance was
      associated with problematic use of pornography. Discussion and conclusions We
      emphasize the role of trait impulsivity across multiple addiction-related
      behaviors. Our findings in at-risk youth highlight urgency and lack of
      perseverance as potential predictors for the development of addictions and as
      potential preventative therapeutic targets.

PMID- 29642725
TI  - Comparison of methods to estimate haemodialysis urea clearance.
AB  - INTRODUCTION: Dialysis adequacy is traditionally measured by monthly blood urea
      sampling and calculating sessional Kt/Vurea. Modern dialysis machines can
      estimate clearances each session, so we wished to compare online measurements
      with standard Kt/Vurea. METHODS: Urea clearance was estimated by intermittent
      changes in effective ionic dialysance and by continuous ultraviolet light
      absorption spent during the mid-week dialysis session. Total body water was
      calculated by the Watson equation and measured by multifrequency bioimpedance.
      RESULTS: We compared Kt/Vurea measurements in 162 patients with online
      assessments: 38 by ultraviolet absorption and 124 by effective ionic dialysance
      (50 Fresenius 4008 and 74 Fresenius 5008). All online measurements overestimated
      single-pool Kt/Vurea (ultraviolet absorption mean bias 0.25 +/- 0.24, effective
      ionic dialysance 4008H 0.25 +/- 0.21 and 5008H 0.20 +/- 0.25; p < 0.001).
      However, there was no difference between dual-pool Kt/V and ultraviolet
      absorbance (1.28 +/- 0.26 vs 1.29 +/- 0.27) or by effective ionic dialysance with
      the 4008 (1.40 +/- 0.26 vs 1.46 +/- 0.33), although the effective ionic
      dialysance 5008 overestimated clearance (1.39 +/- 0.27 vs 1.31 +/- 0.22; p <
      0.01). Similarly, with dual-pool Kt/Vurea, the mean bias for ultraviolet
      absorption was 0.08 +/- 0.35, for effective ionic dialysance (EID) 4008 was 0.13
      +/- 0.55 and for EID 5008 was -0.2 +/- 0.36. Hence, the mean bias was greater
      with the EID 5008 compared to ultraviolet absorption (0.08 +/- 0.35 vs -0.2 +/-
      0.36 vs p < 0.01). CONCLUSIONS: Online measurements allow dialysis adequacy to be
      measured every session. We found that although online clearances overestimated
      single-pool Kt/Vurea measurements, there were no significant differences between
      the continuous ultraviolet light absorbance method and intermittent effective
      ionic dialysance.

PMID- 29642726
TI  - Donkey milk kefir induces apoptosis and suppresses proliferation of Ehrlich
      ascites carcinoma by decreasing iNOS in mice.
AB  - Donkey milk and donkey milk kefir exhibit antiproliferative, antimutagenic and
      antibacterial effects. We investigated the effects of donkey milk and donkey milk
      kefir on oxidative stress, apoptosis and proliferation in Ehrlich ascites
      carcinoma (EAC) in mice. Thirty-four adult male Swiss albino mice were divided
      into four groups as follows: group 1, administered 0.5 ml water; group 2,
      administered 0.5 ml water + EAC cells; group 3, administered 0.5 ml donkey milk +
      EAC cells; group 4, administered 0.5 ml donkey milk kefir + EAC cells. We
      introduced 2.5 x 106 EAC cells into each animal by subcutaneous injection. Tap
      water, donkey milk and donkey milk kefir were administered by gavage for 10 days.
      Animals were sacrificed on day 11. After measuring the short and long diameters
      of the tumors, tissues were processed for histology. To determine oxidative
      stress, cell death and proliferation iNOS and eNOS, active caspase-3 and
      proliferating cell nuclear antigen were assessed using immunohistochemistry. A
      TUNEL assay also was used to detect apoptosis. Tumor volume decreased in the
      donkey milk kefir group compared to the control and donkey milk groups. Tumor
      volume increased in the donkey milk group compared to the control group.
      Proliferating cell nuclear antigen levels were higher in the donkey milk kefir
      group compared to the control and donkey milk groups. The number of apoptotic
      cells was less in the donkey milk group, compared to the control, whereas it was
      highest in the donkey milk kefir group. Donkey milk administration increased eNOS
      levels and decreased iNOS levels, compared to the control group. In the donkey
      milk kefir group, iNOS levels were significantly lower than those of the control
      and donkey milk groups, while eNOS levels were similar to the control group.
      Donkey milk kefir induced apoptosis, suppressed proliferation and decreased co
      expression of iNOS and eNOS. Donkey milk promoted development of the tumors.
      Therefore, donkey milk kefir appears to be more beneficial for treating breast
      cancer than donkey milk.

PMID- 29642727
TI  - LPS challenge increased intestinal permeability, disrupted mitochondrial function
      and triggered mitophagy of piglets.
AB  - Here we investigated the influence of LPS-induced gut injury on antioxidant
      homeostasis, mitochondrial (mt) function and the level of mitophagy in piglets.
      The results showed that LPS-induced intestinal injury decreased the
      transepithelial electrical resistance, increased the paracellular permeability of
      F1TC dextran 4 kDa, and decreased the expression of claudin-1, occludin and
      zonula occludens-1 in the jejunum compared with the control group. LPS decreased
      the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px),
      and increased the content of malondialdehyde in the jejunum. Meanwhile, the
      expression of SOD-related genes ( Cu/Zn-SOD, Mn-SOD) and GSH-Px-related genes (
      GPX-1, GPX-4) declined in LPS-challenged pigs compared with the control. LPS also
      increased TNF-alpha, IL-6, IL-8 and IL-1beta mRNA expression. LPS induced mt
      dysfunction, as demonstrated by increased reactive oxygen species production and
      decreased membrane potential of intestinal mitochondria, intestinal content of mt
      DNA and activities of the intestinal mt respiratory chain. Furthermore, LPS
      induced an increase in expression of mitophagy related proteins, PTEN-induced
      putative kinase (PINK1) and Parkin in the intestinal mitochondria, as well as an
      enhancement of the ratio of light chain 3-II (LC3-II) to LC3-I content in the
      jejunal mucosa. These results suggested that LPS-induced intestinal injury
      accompanied by disrupted antioxidant homeostasis, caused mt dysfunction and
      triggered mitophagy.

PMID- 29642728
TI  - Tunnelling a midline catheter: When the traffic light shifts from yellow to
      green.
AB  - INTRODUCTION:: A safe, largely used practice for difficult venous access patients
      is positioning a catheter in deeper veins under ultrasound guide. However, the
      risk of complications is increased when there is a high catheter-to-vein ratio or
      when the insertion site is in a zone with particular anatomical/physiological
      characteristics. CASE DESCRIPTION:: A 60-year-old woman admitted to a post
      operative intensive care unit after cardiac surgery had a complicated post
      operative course. After the removal of a central venous catheter, it was
      necessary to insert a midline catheter. A complete ultrasound evaluation showed
      that only the axillary vein was suitable for direct cannulation. To avoid
      creating an exit site in the axillary cavity, the decision was made to tunnel the
      catheter to locate an exit site in a safer position. A guidewire was introduced
      through a needle in the axillary vein. A tunnel was created using a subcutaneous
      injection of lidocaine. A 14 G/13.3 cm peripheral venous catheter was inserted in
      the subcutaneous tract. A 4 Fr/20 cm catheter was introduced through the
      peripheral venous catheter and moved to the axillary vein through the previously
      inserted sheath. No acute complications occurred. The catheter was accessed
      several times a day during the period following its insertion to infuse drugs and
      take blood samples. It was removed 50 days after its placement because it was no
      longer needed. No symptomatic thrombosis or infections occurred. CONCLUSION:: The
      placement of the tunnelled midline catheter is shown to be a safe and effective
      way to ensure vascular access for almost 2 months.

PMID- 29642729
TI  - Safety Evaluation of Soy Leghemoglobin Protein Preparation Derived From Pichia
      pastoris, Intended for Use as a Flavor Catalyst in Plant-Based Meat.
AB  - The leghemoglobin protein (LegH) from soy ( Glycine max) expressed in Pichia
      pastoris (LegH preparation, LegH Prep) imparts a meat-like flavor profile onto
      plant-based food products. The safety of LegH Prep was evaluated through a series
      of in vitro and in vivo tests. The genotoxic potential of LegH Prep was assessed
      using the bacterial reverse mutation assay (Ames test) and the in vitro
      chromosome aberration test. LegH Prep was nonmutagenic and nonclastogenic in each
      test, respectively. Systemic toxicity was assessed in a 28-day dietary study in
      male and female Sprague Dawley rats. There were no mortalities associated with
      the administration of LegH Prep. There were no clinical observations, body
      weight, ophthalmological, clinical pathology, or histopathological changes
      attributable to LegH Prep administration. There were no observed effects on male
      reproduction in this study, but the suggestion of a potential estrous cycle
      distribution effect in female rats prompted a second comprehensive 28-day dietary
      study in female Sprague Dawley rats. This study demonstrated that female
      reproductive parameters were comparable between rats treated with LegH Prep and
      concurrent control rats. These studies establish a no observed adverse effect
      level of 750 mg/kg/d LegH, which is over 100 times greater than the 90th
      percentile estimated daily intake. Collectively, the results of the studies
      presented raise no issues of toxicological concern with regard to LegH Prep under
      the conditions tested.

PMID- 29642730
TI  - Long-term outcomes of bovine pericardial patch angioplasty for recurrent stenosis
      in vascular access: A UK single-centre experience.
AB  - INTRODUCTION:: Stenosis of an arteriovenous fistula or arteriovenous graft for
      dialysis is a common problem. Stenosis may lead to a number of problems including
      failure of the fistula. Treatment of stenosis is commonly with percutaneous
      angioplasty or surgical patch angioplasty with autologous vein or synthetic graft
      or patch. Here we report the use of bovine pericardial patch angioplasty as an
      alternative mode of patch angioplasty when percutaneous intervention has failed.
      METHODS:: Patients with fistulae treated with bovine patch angioplasty between
      2013 and 2016 were identified from a prospectively maintained renal access
      database (Cyberren(r)). Patient records were reviewed, noting type and location
      of access, patency, re-interventions and complications post bovine pericardial
      patch. RESULTS:: A total of 40 patients were identified as having undergone
      bovine pericardial patch angioplasty between January 2013 and April 2016. The
      median time from fistula formation to bovine pericardial patch was 15 months
      (interquartile range (IQR): 5-43). Median duration of follow-up was 14 months
      (IQR: 5-18). Primary patency at 6, 12, 18 and 24 months was 91%, 66%, 61% and
      54%, respectively. Secondary patency was 94%, 91%, 80% and 77% at the same time
      points, respectively. In total, 15 patients required 23 re-interventions post
      bovine pericardial patch. There has been no report of infection or aneurysm
      formation. CONCLUSION:: Bovine pericardial patch angioplasty for recurrent
      stenosis in arteriovenous fistulae for dialysis access provides a robust
      alternative to other surgical patches with the added advantage of allowing early
      needling and relative resistance to infection. Rates of restenosis and failure
      post bovine pericardial patch are low.

PMID- 29642731
TI  - The effect of hemodynamically significant patent ductus arteriosus on acute
      kidney injury and systemic hypertension in extremely low gestational age
      newborns.
AB  - BACKGROUND: Acute kidney injury (AKI) in preterm neonates is becoming an
      increasingly recognized morbidity in the neonatal intensive care unit neonatal
      intensive care unit (NICU), yet its epidemiology, delineation and relation to
      numerous toxic exposures and common morbidities such as systemic hypertension is
      just evolving. With a frequency of the patent ductus arteriosus (PDA) as high as
      70% in preterm infants born before 28-week gestation, the role of the
      hemodynamically significant PDA (hs-PDA) remains unclear. OBJECTIVE: To determine
      if AKI and systemic hypertension is more common in extremely low gestational age
      newborns (ELGAN) with hs PDA compared to ELGAN with no or non-hs PDA using
      modified AKIN and Neonatal Risk, Injury, Failure, Loss of Kidney Function, and
      End-stage (N-RIFLE) scoring systems. METHODS: This was a retrospective cohort
      study of infants <=28 weeks gestational age born between 2010 and 2016 who had
      echocardiographic PDA evaluation completed for hemodynamical significance as well
      as serial serum creatinine and urine output measurement documented, needed for
      the two AKI scoring systems: modified AKIN (based on serial serum creatinine) and
      N-RIFLE (using urine output data). Blood pressure measurements and therapy were
      evaluated during the hospitalization and on the day of NICU discharge. Baseline
      characteristics and outcome variables were compared between the hs-PDA and no or
      non-hs PDA using unpaired t-tests for continuous variables and chi square tests
      for categorical data. RESULTS: One hundred fifty-one infants were eligible of
      which 110 had hs-PDA. Infants with hs-PDA were smaller (777 versus 867 g, p =
      .026), less mature (25.8 versus 26.4 weeks, p = .023) and had greater exposure to
      nephrotoxic drugs (14 versus 9.4 days, p = .001). Other clinical and demographic
      variables were similar between the two groups. The overall incidence of AKI was
      not different between the hs-PDA and no PDA or non-hs PDA groups when evaluated
      by the acute kidney injury network (AKIN) or N-RIFLE staging; however, preterm
      newborns with hs-PDA demonstrated a trend towards increased risk of AKI injury
      (12.7 versus 0.02%, p = .06). The N-RIFLE and AKIN scoring systems demonstrated
      very poor degree of agreement (kappa = 0.00853) in our study. There was no
      difference in the rates of hypertension during the hospitalization as well as on
      the day of NICU discharge. CONCLUSION: Preterm neonates with hs-PDA had similar
      rates of AKI and hypertension as neonates with no or non-hs PDA.

PMID- 29642732
TI  - Evaluation of Appropriate Sodium Polystyrene Sulfonate Use With a Hyperkalemia
      Order Set: A Pilot Study.
AB  - BACKGROUND: No consensus guidelines exist to assist practitioners in the
      management of hyperkalemia. Sodium polystyrene sulfonate (SPS) is a common
      treatment option for hyperkalemia. To aid health-care professionals, a
      hyperkalemia order set was created at a 979-bed community teaching hospital.
      OBJECTIVE: The objective of this study was to determine whether use of a
      hyperkalemia order set is associated with appropriate use of SPS. METHODS: Orders
      for SPS were evaluated for appropriateness in this retrospective cohort of adult
      patients. Data were collected from December 1, 2015, to December 31, 2016. All
      orders for SPS not from an order set were randomly matched to those from the
      order set in a 2:1 fashion. Appropriate use was defined as potassium level >5.5
      mEq/L and no contraindications to use. The primary outcome was the absolute
      difference in the proportion of patients with appropriate SPS use in the order
      set group compared to the nonorder set group. RESULTS: A total of 120 patients
      were analyzed, 40 in the order set group and 80 in the nonorder set group.
      Baseline characteristics were similar between the groups. Appropriate use
      occurred in 97.5% of order set patients compared to 60% in the nonorder set group
      ( P < .001). Use of the order set was associated with a greater reduction in
      serum potassium, quicker follow-up potassium level, and lower incidence of
      gastrointestinal adverse effects. CONCLUSIONS: The use of a hyperkalemia order
      set is associated with appropriate use of SPS. Requiring the use of the
      hyperkalemia order set for administration of SPS may enhance patient care and
      safety.

PMID- 29642733
TI  - Warfarin Patients With Anemia Show Trend of Out-of-Range International Normalized
      Ratio Frequency With Point-of-Care Testing in an Anticoagulation Clinic.
AB  - INTRODUCTION: Many factors influence international normalized ratio (INR);
      however, few studies have examined the impact of anemia in warfarin patients. The
      primary objective of this study was to explore the relationship between in-clinic
      anemia and the control of INR within an anticoagulation clinic. METHODS: A
      retrospective chart review was performed on a random sample of patients seen in
      an academic medical center pharmacy-managed anticoagulation clinic. Hemochron(r)
      Signature Elite machine was utilized to monitor point-of-care (POC) INR. In
      clinic anemia was defined as hematocrit <32%. Statistical analyses were conducted
      using STATA MP a webbased platform ( https://www.stata.com/statamp/ ). RESULTS:
      Of the 300 patients analyzed, 45 (15%) patients had in-clinic anemia. Patients
      with in-clinic anemia were more likely to be younger ( P < .05), female ( P <
      .05), and have a diagnosis of sickle cell disease or anemia ( P < .05). In the
      unadjusted logistic regression model, patients with in-clinic anemia were less
      likely to have an in-range INR ( OR: 0.52; 95% CI: 0.27-0.98). The adjusted
      regression model did not show significance. CONCLUSION: Study results suggest
      that in-clinic anemia may be more prevalent among younger, female patients
      prescribed warfarin, and patients diagnosed with in-clinic anemia may be a risk
      factor for out-of-range INR. Pharmacists practicing in anticoagulation clinics
      can incorporate this information into patient care practice in efforts to
      maintain optimal management.

PMID- 29642734
TI  - Language development in children who stutter: A review of recent research.
AB  - PURPOSE: This article reviews recent studies that examined the controversial
      claim that children who stutter (CWS), as a group, have weaker language skills
      than children who do not stutter (CWNS). The article was an effort to address the
      conflicting conclusions of two previous reviews of the research in this area.
      METHOD: Studies published in research journals during the past 7 years (2011
      2018) were located through a systematic review of the literature. Each study was
      analysed to determine how well it supported the claim that CWS, as a group, have
      weaker language skills than CWNS. RESULT: The evidence was not convincing to
      support this controversial claim. Rather, the review indicated that CWS performed
      as well as or better than CWNS on formal language tasks. CONCLUSION: The claim
      that language weaknesses are linked to children's stuttering is not well
      supported by recently published studies. Alternative interpretations of the
      literature are offered.

PMID- 29642735
TI  - Commentary: Below-the-Knee Retrograde Access for Peripheral Interventions: A
      Valuable Technique for the Limb Salvage Toolbox.

PMID- 29642736
TI  - Commentary: Endovascular Sealing of Abdominal Aortic Aneurysms: Do Current Data
      Justify Wider Use?

PMID- 29642737
TI  - Sudden Unexpected Death in Neonates: A Clinico-pathological Study.
AB  - Clinico-pathological studies that focus on sudden unexpected death (SUD) in the
      neonatal period are rare. The objective of this study was to elucidate the
      frequency and pathological spectrum of anatomical causes of death (CODs), found
      in the setting of sudden unexpected death in neonates (SUD-N), and to correlate
      the COD with premortem circumstantial information. We conducted a detailed review
      of all autopsy reports on SUD-N cases at our institution from 1997 to 2015.
      Analyzed clinical data included obstetrical history, postpartum/neonatal medical
      course, and circumstances surrounding death. Evaluated autopsy data included
      growth parameters, pathological findings, ancillary test results, and COD. Data
      from decedents in which a COD was established (COD-E) were statistically compared
      with that from decedents in which the COD was undetermined (COD-U). Of 104
      neonates (M: 49; F: 55) who fulfilled our inclusion criteria, a COD was
      established at autopsy in 46 cases (44%). Infections, congenital abnormalities,
      and inborn errors of metabolism were the most common CODs. Single variables
      statistically more likely to be found in COD-E neonates were clinical history of
      prodromal illness, witnessed loss of vital signs, and evidence of physiological
      stress in the thymus or the liver. A prodrome was statistically more common in
      the COD-E group, but the absence of a prodrome does not reliably exclude COD-E
      cases, since over 50% of these patients were asymptomatic prior to their demise.
      In COD-U neonates, the statistically significant factors were death during sleep,
      death during sleep while "bed"-sharing, "heavy" lungs, and petechial hemorrhages
      on the epicardium or pleura. Given the frequency and wide spectrum of underlying
      pathologies in COD-E neonates, referral of SUD-N cases to pathologists with
      specialized pediatric autopsy expertise is recommended.

PMID- 29642738
TI  - Rats and rabbits as pharmacokinetic screening tools for long acting intramuscular
      depots: case study with paliperidone palmitate suspension.
AB  - Development of prodrug of 9-hydroxyrisperidone (paliperidone) long-acting
      intramuscular injection has enabled delivery over four-week time period with
      improved compliance. The key aim of this work was to establish a reliable
      preclinical model which may potentially serve as a screening tool for judging the
      pharmacokinetics of paliperidone formulation(s) prior to human clinical work.
      Sparse sampling composite study was used in rats, (Wistar/Sprague-Dawley (SD; n =
      10)) and a serial blood sampling study design was used in rabbits (n = 4).
      Animals received intramuscular injection of paliperidone palmitate in the thigh
      muscle at dose of 16 (rats) and 4.5 mg/kg (rabbits). Samples were drawn in rats
      (retro-orbital sinus) and rabbits (central ear artery) and were analysed for
      paliperidone using liquid chromatography-mass spectrometry/ mass spectrometry (LC
      MS/MS) assay. The plasma data was subjected to pharmacokinetic analysis.
      Following intramuscular injection of depot formulation in Wistar/SD rats and
      rabbits, absorption of paliperidone was slow and gradual with median value of
      time to reach maximum concentration (Tmax) occurring on day 7. The exposures
      (i.e. area under the curve (AUC; 0-28) days) were 18,597, 21,865 and 18,120
      ng.h/mL, in Wistar, SD and rabbits, respectively. The clearance was slow and
      supported long half-life (8-10 days). Either one of the two models can serve as a
      research tool for establishing pharmacokinetics of paliperidone formulation(s).

PMID- 29642739
TI  - Care, Compassion, Courage, Commitment, Communication and Competence: The 6 Cs.
AB  - These are words we are all very familiar with and perhaps already some of you may
      be thinking 'oh no not again'. In the document One Year On (NHS England/Nursing
      Directorate 2013), comments from patients have been positive on the care they
      have received, but can we with hand on heart say it happens on a national scale
      at all times? This may be a reason for the continued requests for the inclusion
      of the six Cs as a topic for educational days.

PMID- 29642740
TI  - Maternal periodontal disease and adverse perinatal outcomes: is there an
      association? A hospital-based case-control study.
AB  - OBJECTIVES: The association between maternal periodontal disease and adverse
      perinatal outcomes although extensively studied remains unclear. The aim of this
      study was to evaluate, by a case-control study, conducted in three hospitals the
      association between preterm birth and/or low birth weight (PTB/LBW) and clinical
      parameters of maternal periodontal disease. MATERIAL AND METHODS: Postpartum
      women who gave birth to a newborn PTB/LBW (case group), and postpartum women who
      had babies at full term with normal weight (control group) were included, in 1:2
      ratio. Data were collected through medical records, interview, and periodontal
      clinical parameters. Bivariate analysis was performed to assess the PTB/LBW
      proportion relative to independent variables and multiple logistic regression
      analysis to assess the association between adverse perinatal outcomes and
      independent variables. RESULTS: The sample consisted of 148 cases and 296
      controls. By the 148 postpartum women with PTB/LBW in case group, 126 (87.5%) had
      preterm birth, and 75 (50.7%) had PTB and LBW. The periodontal status and
      generalized periodontitis presence were not associated with any adverse pregnancy
      outcomes. Having made four or more prenatal visits was a protective factor for
      all outcomes. The history of previous PTB/LBW was a risk factor for new cases of
      PTB and PTB and/or LBW. The presence of systemic disease was associated with
      preterm and low birth weight (PTLBW). Preeclampsia and cesarean delivery were
      associated with all outcomes. CONCLUSIONS: The clinical parameters of maternal
      periodontitis were not considered as a risk factor for the studied adverse
      perinatal outcomes. CLINICAL RELEVANCE: The present study demonstrated no
      association between maternal periodontitis and PTB/LBW.

PMID- 29642741
TI  - Effects of transcranial direct current stimulation over the Broca's area on
      tongue twister production.
AB  - PURPOSE: The present study aimed to explore the short-term effect of anodal
      transcranial direct current stimulation (tDCS) on tongue twister production.
      METHOD: Thirty healthy native Cantonese adult speakers were randomly assigned to
      the anodal tDCS group or the sham tDCS group. Anodal tDCS of 2 mA was applied
      over the Broca's area of the brain. The stimulation lasted for 20 min for the
      anodal tDCS group and 30 s for the sham tDCS group. The participants were
      instructed to produce a list of tongue twisters before, immediately after and 4 h
      after tDCS. RESULT: Speech rate and response accuracy measured immediately after
      stimulation were significantly faster and higher, respectively, than before
      stimulation. Although there was no change in speech rate measured at 4 h after
      stimulation, response accuracy at that time point was significantly lower than
      that measured immediately after stimulation. However, there were no significant
      differences between the anodal tDCS and sham tDCS groups in either speech rate or
      response accuracy. CONCLUSION: The findings revealed that a single session of
      anodal tDCS over the Broca's area did not significantly improve speech production
      during tongue twister production.

PMID- 29642742
TI  - Career Opportunities for Theatre Practitioners.
AB  - 'What's the point in doing that?' This is often the response given to those
      saying they are undertaking education outside of work hours. Many do not see
      their role in theatre as just a job, but now want a career which means extra
      studying. Ideally this needs to be in advance so they are one step ahead for when
      an opportunity arises. Career opportunities and education go hand in hand
      together, and so it is difficult to discuss one without mentioning the other to
      some degree. We need education to access career opportunities, but we also need
      career routes to help drive education forward.

PMID- 29642743
TI  - Initiative for Burnout of ICU Caregivers: Feasibility and Preliminary Results of
      a Psychological Support.
AB  - BACKGROUND: Intensive care unit (ICU) caregivers are at high risk of burnout and
      the shortage of this highly specialized personal is a problem. The feasibility
      and impact of a psychological intervention were never assessed in this special
      context. METHODS: A randomized controlled single-blind study in an ICU. The first
      intervention consisted in weekly problem-based sessions led by psychologists with
      small groups of caregivers using a systemic approach over 3 months. The modified
      intervention was lead for 9 months. The scores of Maslach Burnout Inventory and
      Hospital Anxiety and Depression Scale were compared between the intervention and
      control groups, before and after the intervention. RESULTS: One-hundred and sixty
      six caregivers were randomized in intervention and control groups. The major
      finding was the way the psychologists could modify the original methodology in
      order to enable caregivers to attend the sessions. Burnout scores tended to
      decrease across the whole ICU team after the intervention period, more in the
      intervention group. Participation in the study was poor at 6 months after
      intervention. CONCLUSIONS: This is the first study attempting to evaluate a
      psychological intervention on the mental health of ICU caregivers. It shows a
      modified method of a psychological support with a systemic approach in the
      special environment of ICU. Notwithstanding the modest results related to the
      short length of the process and the turnover of the personal, we demonstrated
      that such an approach is feasible. Further studies on larger scale and of longer
      duration are needed to investigate the effect of such interventions on the mental
      health of ICU caregivers.

PMID- 29642744
TI  - Evaluation of Continuous Infusion Vancomycin Administration in a Critically Ill
      Trauma Population.
AB  - Vancomycin is a first-line antibiotic for empiric treatment of gram-positive
      infections in the trauma intensive care unit. When dosed intermittently,
      difficulties arise from trough collection and drug monitoring. The objective of
      this study was to evaluate time to goal vancomycin levels comparing a continuous
      infusion protocol when compared to standard intermittent infusion dosing. This
      was a retrospective cohort of patients admitted to the trauma intensive care unit
      between July 2011 and July 2015 receiving vancomycin for at least 48 hours. In
      this cohort of 150 patients, continuous infusion vancomycin had a decreased time
      to goal vancomycin level (2.5 vs 3.8 days, P <= .05) with a higher incidence of
      target attainment (60% vs 40%, P <= .05). This reflected in a decrease in average
      number of blood samples per patient (1 vs 3, P <= .05) and shorter duration of
      therapy (3.8 vs 6.8 days, P <= .05). Patients receiving continuous infusion
      vancomycin also experienced less nephrotoxicity (21% vs 43%, P <= .05). Patients
      in the intermittent infusion group had more missed levels and doses, with only 1
      in every 3 patients receiving all intended doses on time. Vancomycin continuous
      infusion resulted in a decrease in time to goal therapeutic vancomycin levels,
      number of blood samples required, and therapy duration. Larger trials are needed
      to validate these outcomes in broad patient groups and to validate the clinical
      implication and potential cost savings of these results.

PMID- 29642745
TI  - Sharing and Learning.
AB  - The NHS Litigation Authority (NHS LA) is a not-for-profit NHS organisation that
      manages negligence and other claims against the NHS in England on behalf of their
      member organisations. Their overarching vision is to resolve claims in a timely
      and fair manner while sharing the lessons of why things go wrong and improving
      safety.

PMID- 29642747
TI  - Elevated maternal serum-free beta-human chorionic gonadotropin (beta-hCG) and
      reduced risk of spontaneous preterm delivery.
AB  - OBJECTIVE: To evaluate the relationship between first and second trimester
      maternal serum-free beta-hCG and the risk of spontaneous preterm delivery (PTD).
      STUDY DESIGN: This was a case-control study of women evaluated and delivered at
      our institution from 2011 to 2015. Spontaneous PTD was defined as delivery before
      37 weeks due to spontaneous preterm labor or premature rupture of membranes.
      Patient with multifetal gestation and those with medically indicated term or PTD
      were excluded. RESULTS: Of 877 women meeting the inclusion criteria, 173
      delivered preterm and 704 delivered at term, and 8.1% had high free beta-hCG in
      one or both trimesters. High maternal first and/or second trimester free beta-hCG
      (>=95th percentile) was associated with lower rates of PTD. Thirty-two women with
      high free beta-hCG in both first and second trimesters delivered at term.
      Gestational age at delivery and birth weights were lower in women who did not
      have high free beta-hCG in any trimester. Low free beta-hCG (<=5th percentile) in
      either trimester was not associated with an increased or decreased likelihood of
      PTD. Logistic regression demonstrated an independent association of high free
      beta-hCG (>=95th percentile) with a reduced likelihood of PTD. Stratified
      analysis revealed a stronger impact of this association in women with no prior
      history of PTD. CONCLUSIONS: High free beta-hCG, in the absence of risk factors
      for medically indicated PTD, is associated with a reduced likelihood of
      spontaneous PTD and may represent a marker indicating lower risk.

PMID- 29642746
TI  - Biologically and chemically important hydrazino-containing imidazolines as
      antioxidant agents.
AB  - Biologically and chemically useful hydrazinoimidazolines were evaluated as
      antioxidant and antihaemolytic agents. 1,1-Diphenyl-2-picrylhydrazyl radical
      (DPPH*), galvinoxyl radical (GOR), nitric oxide (NO) and hydrogen peroxide (H2O2)
      scavenging assays, ferric ions reducing power assay, and ex vivo model of rat
      erythrocytes exposed to 2,2'-azobis(2-methylpropionamidine)dihydrochloride (AAPH)
      or H2O2 were used. The most potent DPPH* scavengers proved to be
      hydrazinoimidazolines 3, 2, and 4, revealing excellent antiradical effects -
      superior or comparable to that of all antioxidant standards used. Moreover, these
      molecules showed strong NO neutralising potencies - better to that of ascorbic
      acid (AA) (3), 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox) (3
      and 2), butylated hydroxytoluene (BHT) (3 and 2), and butylated hydroxyanisole
      (BHA) (3, 2, and 4). Compound 4 was also effective in GOR scavenging. The
      excellent scavenger of GOR, NO, and H2O2 proved to be structure 5, with the
      potency superior or comparable to the majority of antioxidant standards used. In
      turn, compound 9 was effective in H2O2 and GOR neutralisation. All
      hydrazinoimidazolines revealed the reducing power that is higher than BHT.
      Moreover, the protective effects of most test compounds on oxidatively stressed
      erythrocytes were observed. Some structure-activity relationships were disclosed.
      A significance of the primary hydrazino group on antioxidant effects was
      confirmed. The most likely DPPH* and GOR scavenging mechanisms for test compounds
      were propound. Among all the investigated molecules, hydrazinoimidazolines 5, 3,
      2, 4, and 9, due to their excellent or good antiradical activities, can represent
      promising antioxidant candidates with prospective utility for prevention of
      diseases related to reactive oxygen/nitrogen species.

PMID- 29642748
TI  - Career Opportunities for Theatre Practitioners.
AB  - Never have there been such a vast number of career opportunities for all levels
      of staff within the perioperative environment including healthcare support
      workers, operating department practitioners and nurses.

PMID- 29642750
TI  - The optic pathway: the development of an eLearning animation.
AB  - The optic pathway is responsible for sending visual information from the eyes to
      the brain via electrical impulses. It is essential that a sound understanding of
      this pathway is established in order to determine an accurate diagnosis
      concerning visual field defects. Although easy for trained neurologists to
      understand, it is an area which medical students repeatedly struggle to
      visualise. It is proposed that audio-visual teaching resources can improve
      students understanding of complex areas of importance. This article describes the
      development and evaluation of a short animation created for use in the
      undergraduate neurology curriculum at the University of Dundee School of
      Medicine.

PMID- 29642751
TI  - Bone regeneration strategy by different sized multichanneled biphasic calcium
      phosphate granules: In vivo evaluation in rabbit model.
AB  - A variety of synthetic materials are currently in use as bone substitutes, among
      them a new calcium phosphate-based multichannel, cylindrical, granular bone
      substitute that is showing satisfactory biocompatibility and osteoconductivity in
      clinical applications. These cylindrical granules differ in their mechanical and
      morphological characteristics such as size, diameter, surface area, pore size,
      and porosity. The aim of this study is to investigate whether the sizes of these
      synthetic granules and the resultant inter-granular spaces formed by their
      filling critical-sized bone defects affect new bone formation characteristics and
      to determine the best formulations from these individual types by combining the
      granules in different proportions to optimize the bone tissue regeneration. We
      evaluated two types of multichanneled cylindrical granules, 1 mm and 3 mm in
      diameter, combined the granules in two different proportions (wt%), and compared
      their different mechanical, morphological, and in vitro and in vivo
      biocompatibility characteristics. We assessed in vitro biocompatibility and
      cytotoxicity using MC3T3-E1 osteoblast-like cells using MTT (3-(4,5
      Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and confocal
      imaging. In vivo investigation in a rabbit model indicated that all four samples
      formed significantly better bone than the control after four weeks and eight
      weeks of implantation. Micro-computed tomography analysis showed more bone
      formation by the 1 mm cylindrical granules with 160 +/- 10 um channeled pore and
      50% porosity than the other three samples ( p<.05), which we confirmed by
      histological analysis.

PMID- 29642749
TI  - Chronic migraine: A process of dysmodulation and sensitization.
AB  - Chronic migraine is a common chronic daily headache featured by frequent headache
      attacks with at least 15 headache days per month, which brings great disease
      burden to both the sufferers and the society. Transformed from episodic migraine,
      the pathophysiology of chronic migraine is not fully understood, even though
      several risk factors have been associated with migraine progression. Recent
      studies have identified both structural and functional alterations in some brain
      regions of chronic migraine patients indicating that maladaptation of the top
      down pain modulation and subsequent sensitization of trigeminal system may be
      important in the pathogenesis of chronic migraine. Moreover, biochemical analysis
      has confirmed several molecules related to chronic migraine, which may serve as
      biomarkers and potential therapeutic targets. Chronic migraine is undertreated
      because of its poor treatment response and limited therapy options. In this
      article, we reviewed the latest data to outline the clinical feature,
      pathophysiological mechanism, and management of chronic migraine, in the
      expectation to provide direction for future research and finally to take good
      care of chronic migraine patients.

PMID- 29642752
TI  - Lupus myocarditis: a single center experience and a comparative analysis of
      observational cohort studies.
AB  - Background Lupus myocarditis (LM) is reported in 3-9% of patients with systemic
      lupus erythematosus (SLE) but limited evidence exists regarding optimal treatment
      and prognosis. This study aims to describe LM in a defined lupus cohort as
      compared with the existing literature. Patients and methods Patients with LM were
      identified from the University of Toronto Lupus Clinic database. Diagnosis was
      based on clinical manifestations and electrocardiographic, imaging, and
      biochemical criteria. Demographic, clinical, diagnostic and therapeutic variables
      and outcomes were collected in a standardized data retrieval form. A literature
      review was performed to identify cohort studies reporting on LM treatment and
      outcome. A comparative analysis was conducted between our patients and the
      combined cohort of the existing studies. Results Thirty patients were diagnosed
      with LM (prevalence 1.6%) and compared with a cumulative cohort of 117 patients
      from five distinct studies. No significant differences were found regarding the
      age at diagnosis (32.6 +/- 13.4 years) and SLE duration (2.5 years median).
      Concomitant lupus activity from other organ systems was observed in 97% of the
      patients. Chest pain was more frequently reported in our cohort whereas dyspnea
      was more prominent in the other studies. Diagnostic criteria were similar across
      studies. Therapeutic approach was comparable and consisted of
      glucocorticosteroids (96.6%) and immunosuppressives (70%). Mortality was
      approximately 20% whereas another 20% of the patients achieved partial and 60%
      complete recovery. Conclusions LM usually occurs early in the disease course and
      in the context of generalized lupus activity. Despite aggressive therapy,
      approximately 40% of the patients died or had residual heart damage.

PMID- 29642753
TI  - Determination of olaquindox, carbadox and cyadox in animal feeds by ultra
      performance liquid chromatography tandem mass spectrometry.
AB  - Olaquindox, carbadox, and cyadox are chemically synthesised antibacterial and
      growth-promoting agents for animals. At high doses they may exert mutagenicity
      and hepatic and adrenal toxicities in animals. Regrettably, these substances are
      frequently abused or misused when added into animal feeds. Thus, developing a
      sensitive and reliable method for simultaneous determination of olaquindox,
      carbadox, and cyadox in different kinds of animal feeds is crucially important
      for food safety monitoring. In this paper we optimised instrumental conditions,
      extraction solvents, solid phase extraction cartridges, and pH of the loading
      solvents on the Oasis HLB cartridge. Under the optimal conditions, mean
      recoveries ranged from 74.1 to 111%, and intra-day and inter-day variations were
      lower than 14.6% and 10.8%, respectively. The limits of quantification for
      olaquindox, carbadox, and cyadox were 0.05 mg kg-1, 0.10 mg kg-1, and 0.025 mg kg
      1, respectively. The proposed method uses ultra-performance liquid chromatography
      tandem mass spectrometry and is sensitive and reliable for the simultaneous
      determination of olaquindox, carbadox, and cyadox in three kinds of animal feeds
      (specifically, mixed feed, concentrated feed, and additive premixed feed). This
      method has good precision, high sensitivity, and good reproducibility, and thus
      it can be used for convenient and accurate determination of olaquindox, carbadox,
      and cyadox in different kinds of animal feeds.

PMID- 29642754
TI  - Daily gentamicin using ideal body weight demonstrates lower risk of postpartum
      endometritis and increased chance of successful outcome compared with traditional
      8-hour dosing for the treatment of intrapartum chorioamnionitis.
AB  - BACKGROUND: Clinical chorioamnionitis complicates approximately 1-4% of
      pregnancies overall. Although universal agreement does not exist regarding the
      antibiotic regimen of choice, most studies have evaluated intravenous ampicillin
      dosed at 2 g every 6 hours plus gentamicin dosed every 8 hours. Only three
      studies have examined daily gentamicin for the treatment of intrapartum
      chorioamnionitis and thus is insufficiently investigated. OBJECTIVE: This study
      seeks to determine whether daily dosing of gentamicin using ideal body weight for
      the treatment of intrapartum chorioamnionitis is more or equivalently efficacious
      when compared to traditional 8-hour dosing regimens. MATERIALS AND METHODS: We
      conducted a retrospective cohort study and reviewed charts on all women receiving
      treatment for intrapartum chorioamnionitis, which included intravenous gentamicin
      daily dosing calculated using 5 mg/kg ideal body weight or receiving traditional
      every 8 hours dosing of gentamicin at two large academic centers. Our primary
      outcomes were resolution of infection following delivery without the development
      of maternal endometritis and/or neonatal sepsis. Baseline characteristics were
      compared between dosing groups using Welch two-sample t-tests for continuous
      variables, uncorrected X2 test and exact binomial 95% confidence intervals. We
      calculated the risk ratios of each outcome in the ideal versus traditional dosing
      groups using modified Poisson regression, both crude and adjusted. Adjusted
      models were controlled for variables determined to be potential confounders,
      which included BMI, diabetes mellitus, gestational blood pressure >140/90, group
      beta-Streptococcus status, race, advanced maternal age (>34 y), and parity.
      RESULTS: The study included 500 patients with 255 patients receiving daily dosing
      of gentamicin and 245 receiving traditional dosing of gentamicin. Of the patients
      receiving daily gentamicin compared to traditional dosing, 95.7% (95% CI 94.9
      96.6%) achieved the primary outcome versus 92% (95% CI 90.8 - 93.2%), 2.4% (95%
      CI 1.8-3%) developed endometritis versus 5.6% (4.5-6.7%), 1.6% (95% CI 1.1-2.1%)
      delivered neonates with sepsis versus 3.3% (CI 2.5-4.1%), and 36.9% required
      cesarean delivery versus 41.4%. In crude analysis, compared to traditional
      dosing, IDW daily dosing was associated with a lower risk of postpartum
      endometritis (RR 0.42, 95% CI 0.16-1.10, p = .032). After adjusting for BMI,
      diabetes mellitus, gestational blood pressure >140/90, group beta-Streptococcus
      status, race, advanced maternal age (>34 y), and parity, the IDW daily dosing
      group had a 5% greater chance of successful outcome (RR 1.05, 95% CI 1.00-1.10, p
      = .046) and a 64% lower risk of endometritis (RR 0.35, 95% CI 0.15-0.83, p =
      .017). CONCLUSION: Daily dosing of gentamicin using ideal body weight is
      associated with a lower risk of postpartum endometritis and high chance of a
      successful outcome in the treatment of intrapartum chorioamnionitis compared with
      traditional 8-hour dosing in our ethnically diverse, urban population and thus
      may be considered a superior option to every 8 hours dosing regimens.

PMID- 29642755
TI  - Successful treatment of ventricular arrhythmic storm with percutaneous coronary
      intervention and catheter ablation in a patient with left ventricular assist
      device.
AB  - INTRODUCTION: Ventricular arrhythmias are common in patients with advanced heart
      failure, which may also persist after sufficient intensive therapy for heart
      failure even with a left ventricular assist device. Although most ventricular
      arrhythmias have no hemodynamic relevance during left ventricular assist device
      support, some patients suffer from right ventricular decompensation due to
      ventricular arrhythmias resulting in severe hemodynamic deterioration and poor
      clinical outcomes. METHODS: We describe herein an left ventricular assist device
      patient with refractory ventricular arrhythmic storm early after left ventricular
      assist device implantation. RESULTS: The patient was admitted to our department
      after stenting of left anterior descending artery with subsequent polymorphic
      ventricular tachycardia and cardiogenic shock with ongoing multi-organ failure.
      After 6 days of extracorporeal life-support, a permanent left ventricular assist
      device was implanted. With postoperatively ongoing tachycardias, a subtotal right
      coronary artery occlusion was recanalized utilizing a drug-eluting stent. On the
      first post-intervention day, an additional catheter ablation was successfully
      performed. No further ventricular tachycardias were detected during the entire
      hospital stay and the further postoperative course was uneventful. The patient
      was transferred to a physiotherapy unit to improve his daily physical activities.
      He is currently at home and doing well 6 months after discharge. CONCLUSIONS: Our
      case report demonstrates the feasibility of a successful therapeutic approach
      with a combination of interventional therapies such as coronary stenting and
      catheter ablation in a patient with persistent ventricular arrhythmias after
      assist device implantation.

PMID- 29642756
TI  - The effect of visual arrangement on visuospatial short-term memory: Insights from
      children with 22q11.2 deletion syndrome.
AB  - Recent models of visuospatial (VSSP) short-term memory postulate the existence of
      two dissociable mechanisms depending on whether VSSP information is presented
      simultaneously or sequentially. However, they do not specify to what extent VSSP
      short-term memory is under the influence of general VSSP processing. This issue
      was examined in people with 22q11.2 deletion syndrome, a genetic condition
      involving a VSSP deficit. The configuration of VSSP information was manipulated
      (structured vs. unstructured) to explore the impact of arrangement on VSSP short
      term memory. Two presentation modes were used to see whether the VSSP arrangement
      has the same impact on simultaneous and sequential short-term memory. Compared to
      children matched on chronological age, children with 22q11.2 deletion syndrome
      showed impaired performance only for structured arrangement, regardless of the
      presentation mode, suggesting an influence of VSSP processing on VSSP short-term
      memory abilities. A revised cognitive architecture for a model of VSSP short-term
      memory is proposed.

PMID- 29642757
TI  - Associations between chronotype, morbidity and mortality in the UK Biobank
      cohort.
AB  - Later chronotype (i.e. evening preference) and later timing of sleep have been
      associated with greater morbidity, including higher rates of metabolic
      dysfunction and cardiovascular disease (CVD). However, no one has examined
      whether chronotype is associated with mortality risk to date. Our objective was
      to test the hypothesis that being an evening type is associated with increased
      mortality in a large cohort study, the UK Biobank. Our analysis included 433 268
      adults aged 38-73 at the time of enrolment and an average 6.5-year follow-up. The
      primary exposure was chronotype, as assessed through a single self-reported
      question-defining participants as definite morning types, moderate morning types,
      moderate evening types or definite evening types. The primary outcomes were all
      cause mortality and mortality due to CVD. Prevalent disease was also compared
      among the chronotype groups. Analyses were adjusted for age, sex, ethnicity,
      smoking, body mass index, sleep duration, socioeconomic status and comorbidities.
      Greater eveningness, particularly being a definite evening type, was
      significantly associated with a higher prevalence of all comorbidities. Comparing
      definite evening type to definite morning type, the associations were strongest
      for psychological disorders (OR 1.94, 95% CI 1.86-2.02, p = < 0.001), followed by
      diabetes (OR 1.30, 95% CI 1.24-1.36, p = < 0.001), neurological disorders (OR
      1.25, 95% CI 1.20-1.30, p = < 0.001), gastrointestinal/abdominal disorders (OR
      1.23, 95% CI 1.19-1.27, p = < 0.001) and respiratory disorders (OR 1.22, 95% CI
      1.18-1.26, p = < 0.001). The total number of deaths was 10 534, out of which 2127
      were due to CVD. Greater eveningness, based on chronotype as an ordinal variable,
      was associated with a small increased risk of all-cause mortality (HR 1.02, 95%
      CI 1.004-1.05, p = 0.017) and CVD mortality (HR 1.04, 95% CI 1.00-1.09, p =
      0.06). Compared to definite morning types, definite evening types had
      significantly increased risk of all-cause mortality (HR 1.10, 95% CI 1.02-1.18, p
      = 0.012). This first report of increased mortality in evening types is consistent
      with previous reports of increased levels of cardiometabolic risk factors in this
      group. Mortality risk in evening types may be due to behavioural, psychological
      and physiological risk factors, many of which may be attributable to chronic
      misalignment between internal physiological timing and externally imposed timing
      of work and social activities. These findings suggest the need for researching
      possible interventions aimed at either modifying circadian rhythms in individuals
      or at allowing evening types greater working hour flexibility.

PMID- 29642761
TI  - The Lighthouse and the Observatory: Islam, Science, and Empire in Late Ottoman
      Egypt.

PMID- 29642758
TI  - Identification of Significant Gene Signatures and Prognostic Biomarkers for
      Patients With Cervical Cancer by Integrated Bioinformatic Methods.
AB  - Cervical cancer is the leading cause of death with gynecological malignancies. We
      aimed to explore the molecular mechanism of carcinogenesis and biomarkers for
      cervical cancer by integrated bioinformatic analysis. We employed RNA-sequencing
      details of 254 cervical squamous cell carcinomas and 3 normal samples from The
      Cancer Genome Atlas. To explore the distinct pathways, messenger RNA expression
      was submitted to a Gene Set Enrichment Analysis. Kyoto Encyclopedia of Genes and
      Genomes and protein-protein interaction network analysis of differentially
      expressed genes were performed. Then, we conducted pathway enrichment analysis
      for modules acquired in protein-protein interaction analysis and obtained a list
      of pathways in every module. After intersecting the results from the 3
      approaches, we evaluated the survival rates of both mutual pathways and genes in
      the pathway, and 5 survival-related genes were obtained. Finally, Cox hazards
      ratio analysis of these 5 genes was performed. DNA replication pathway ( P <
      .001; 12 genes included) was suggested to have the strongest association with the
      prognosis of cervical squamous cancer. In total, 5 of the 12 genes, namely,
      minichromosome maintenance 2, minichromosome maintenance 4, minichromosome
      maintenance 5, proliferating cell nuclear antigen, and ribonuclease H2 subunit A
      were significantly correlated with survival. Minichromosome maintenance 5 was
      shown as an independent prognostic biomarker for patients with cervical cancer.
      This study identified a distinct pathway (DNA replication). Five genes which may
      be prognostic biomarkers and minichromosome maintenance 5 were identified as
      independent prognostic biomarkers for patients with cervical cancer.

PMID- 29642759
TI  - Cannabis use and knowledge among medical students at the University of the Free
      State, Bloemfontein, South Africa.
AB  - OBJECTIVE: The study aimed to investigate the prevalence of cannabis use among
      undergraduate medical students of the University of the Free State (UFS), and the
      extent of their knowledge about the substance. METHOD: This cross-sectional study
      included five year groups of undergraduate medical students. A self-administered,
      anonymous questionnaire was used. RESULTS: Of the 643 medical students, 541
      (84.1%) completed the questionnaire. In total, 161 (30.9%) students reported that
      they had ever used cannabis. The percentage of males who had ever used cannabis
      was twice that of females (relative risk 2.04; 95% CI 1.56; 2.67). Of the
      cannabis users, less than 12% used it monthly or more often. A fifth (19.5%) of
      all students stated that they did not know the side effects of cannabis use.
      Nearly half (45.4%) indicated that they could not name any medicinal (medical)
      uses. The median knowledge score of students who used cannabis tended to be
      higher than that of students who did not use cannabis; this was statistically
      significant only in the third-year group. CONCLUSIONS: Medical students generally
      have a low level of knowledge about cannabis. The reported lifetime prevalence
      and pattern of cannabis use are similar to those reported in other South African
      studies published over the past 35 years.

PMID- 29642763
TI  - Hot off the Press for Perioperative Nurses.
AB  - I am delighted to bring you the Perioperative Care Collaborative (PCC) National
      Core Curriculum for Perioperative Nursing 2017, whose purpose is 'influencing and
      supporting clinical policies into perioperative practice'. This is a very
      important document for nurses working within operating theatre settings. Since
      the dissolution of the English National Board (ENB), perioperative nurses have
      not had access to appropriate professional courses in line with what had been
      previously available.

PMID- 29642764
TI  - Distinct effects of resveratrol on seizures and hyperexcitability induced by NMDA
      and 4-aminopyridine.
AB  - OBJECTIVES: The antiepileptic activity of resveratrol has been revealed in
      various experimental models of epilepsy. The present study evaluated the effects
      of resveratrol on the seizures and hyperexcitable neuronal activity associated
      with activation of N-methyl-d-aspartic acid (NMDA) receptor and inhibition of
      voltage-gated potassium channels. METHODS: The effects of resveratrol on seizure
      thresholds, excitatory field potentials (EFPs) and action potentials induced by
      NMDA and 4-aminopyridine (4-AP) were monitored in mice, the mouse cortical slices
      and rat cortical neurons, respectively. RESULTS: Resveratrol increased the NMDA
      induced seizure thresholds and suppressed the frequency of NMDA/glycine-evoked
      EFPs and action potentials. However, resveratrol lowered the 4-AP-induced
      thresholds for myoclonic twitch and face and forelimb clonus, yet enhanced the
      thresholds for running and bouncing clonus and tonic hindlimb extension at the
      higher dose (50 mg/kg). A similar biphasic response of resveratrol was observed
      in the frequency of EFPs and action potential firings evoked by 4-AP, with
      enhancement at lower concentrations, but suppression at higher concentrations.
      DISCUSSION: These findings suggest that resveratrol might be capable of
      protecting against the seizure types related to neuronal excitability and
      progression mediated by NMDA receptor activation, but not suitable for the
      seizures caused by disturbance of the voltage-dependent potassium channels.

PMID- 29642765
TI  - Come Clean for Surgery.
AB  - When patients are brought to the operating theatre a series of checks are
      performed to reduce harm or potential harm to our patients. One harm that can
      cause significant morbidity and mortality to our patients is surgical site
      infection (SSI). Reducing SSIs requires a multi-faceted approach prior to the
      incision. Prophylactic antibiotics are given, if indicated, along with glucose
      and temperature control as part of an SSI bundle. Meticulous attention is paid by
      the team to ensure that the surgical field is prepared with antiseptic solutions
      such as chlorhexidine or betadine. The airflow changes in theatres also help
      minimise the risk of infection. The surgeon and scrub team are trained to
      undertake strict asepsis when 'scrubbing up'. The rest of the team are careful to
      ensure hand hygiene and appropriate glove use at all times.

PMID- 29642766
TI  - Trauma-Related Sleep Problems and Associated Health Outcomes in Police Officers:
      A Path Analysis.
AB  - Police officers are frequently exposed to two different types of potentially
      traumatic events: one dealing with physical threats to self and the other
      involving the witnessing of harm to others. These different types of traumatic
      experiences are thought to produce various posttraumatic reactions. Furthermore,
      sleep problems are also reported as a hallmark of posttraumatic stress disorder.
      There is evidence, however, that sleep problems may mediate the relationship
      between posttraumatic stress disorder symptoms and health outcomes, especially
      physical health and depression. Previous research has shown this to be the case
      among officers from large urban agencies. The purpose of the present study was to
      test a model involving a pathway from trauma type and posttraumatic stress
      disorder symptoms to physical health and depression that is mediated by sleep
      quality in officers ( N = 193) using data from small- to mid-size police
      agencies. Results revealed that sleep problems served as a mediator between
      posttraumatic stress disorder hyperarousal and avoidance symptoms and health
      outcomes, that the trauma types are related to different posttraumatic stress
      disorder symptoms, and that complicated relationships exist between the study
      variables. In addition, the results indicated that approximately 25% of our
      sample displayed probable partial posttraumatic stress disorder or probable full
      posttraumatic stress disorder, causing substantial functional impairment.
      Suggestions for improving officer health and performance in the field are
      provided. Specifically, it appears that interventions designed to address
      posttraumatic stress disorder hyperarousal symptoms related to personal life
      threat and the posttraumatic stress disorder avoidance symptoms related to the
      witnessing of human suffering may maximize officer sleep quality and ultimately
      overall wellness. In particular, mindfulness-based interventions are well suited
      for addressing these symptom clusters.

PMID- 29642767
TI  - The Role of Social Support on Depression Among Vulnerable Caregivers Reporting
      Bidirectional Physical Violence.
AB  - Intimate partner violence (IPV) is a public health concern found across genders,
      socioeconomic strata, cultures, and ethnicities. While IPV is traditionally
      examined from either the victim or initiator role, it is also important to
      consider relationships in which both partners experience and demonstrate
      violence. The current study examined the relation between IPV chronicity and
      depression among 403 female caregivers with young children. Specifically, the
      current study examined the association between bidirectional IPV and depression.
      Furthermore, the impact of social support on depression levels among those
      caregivers was assessed. Results suggest that of those couples who experienced
      violence, bidirectional IPV was reported significantly more frequently than
      unidirectional IPV only. No significant differences in depression were found
      between those reporting bidirectional versus unidirectional IPV. Among those
      involved in bidirectional IPV, having greater social support was associated with
      significantly lower depression levels. Findings suggest that both initiation and
      experiences of IPV should be assessed among caregivers of vulnerable children.
      The potential impact of social support was also identified in this study.
      Clinicians may consider assessing family violence broadly, including
      bidirectional IPV, particularly among parents of young children with other
      adverse life conditions. Development and sustainment of healthy relationships
      through social support may facilitate adjustment for the caregivers.

PMID- 29642768
TI  - Experiences of Gender-Based Violence at a South African University: Prevalence
      and Effect on Rape Myth Acceptance.
AB  - Instances of gender-based violence (GBV) on university campuses are rarely
      reported to the authorities. This makes it difficult to gauge the prevalence of
      this problem, which in turn affects efforts for prevention. This article
      describes a university-wide online survey aimed at assessing, first, the
      prevalence of GBV experienced by the three sectors in the community-students,
      academic and research staff, and professional/administrative staff. Many of the
      findings concurred with research elsewhere-students were the predominant victims
      of GBV; men were the main perpetrators; and instances of rape occurred mainly
      when the victim/survivor was under the influence of alcohol or drugs. In contrast
      to some of the more well-known U.S. surveys (e.g., Georgetown University), we
      found relatively few instances of students being exploited by staff members.
      Occurrences of contrapower harassment were also reported in our survey. The
      second aim investigated whether rape myth acceptance was related to experiences
      of GBV. We found that women who had these experiences were more rejecting of rape
      myths than women who had not had such experiences. The opposite was found for
      White men. White men who had experienced GBV were more accepting of the rape
      myths than those who had not had such experiences. It was suggested that this
      reflected a need for these male victims to establish their hegemonic masculine
      identity. In general, the level of rape myth acceptance was relatively low. This
      suggested that widespread victim-blame, and self-blame does not account for the
      low levels of GBV reports to officials. A limitation of the study was the
      relatively low response rate (1,350 respondents), which was likely caused by the
      student protests over university fees that were ongoing at the time of the
      survey. These protests caused considerable disturbance for all sectors of the
      university community.

PMID- 29642769
TI  - Themes of Healing and Posttraumatic Growth in Women Survivors' Narratives of
      Intimate Partner Violence.
AB  - Research on the effects of intimate partner violence (IPV) on women demonstrates
      the significant physical, emotional, psychological, and spiritual consequences of
      this form of interpersonal trauma. It is well documented that experiencing IPV
      can have devastating consequences to women's physical and mental health, overall
      well-being, and quality of life, as well as that of their children's. However, a
      small, predominantly qualitative body of research exists on women's experience of
      and capacity for healing from the effects of IPV, but more research is needed to
      advance theory and practice in this important area. This study applied secondary
      analysis to an existing data set to answer the question, "What are the themes of
      healing and posttraumatic growth in ten diverse women's narratives of IPV?"
      Lengthy, detailed interview transcripts were rigorously subjected to inductive
      and deductive thematic analysis, which revealed three overarching themes, and six
      subthemes, of healing and posttraumatic growth in women's narratives: Awareness
      and Insight (subthemes: Discerning the Self and Understanding Relationships),
      Renewal and Reconstruction (subthemes: [Re]building the Self and Redefining
      Relationships), and Transformation and Meaning (subthemes: New Perspectives and
      Finding Purpose Through Helping Others). Findings further revealed that women's
      healing from the effects of IPV involves a multidimensional, personalized,
      nonlinear, and often transformative process that operates within themselves and
      through relationships. Practitioners working with women who have experienced IPV
      should consider survivors' potential for healing and target appropriate
      intervention strategies. Additional qualitative and longitudinal research with
      diverse populations would deepen understanding of the dynamics, variables, and
      circumstances that impact healing and posttraumatic growth for women exposed to
      IPV.

PMID- 29642770
TI  - Providing Coordinated, Immediate, Trauma-Focused, and Interdisciplinary Responses
      to Children Exposed to Severe Intimate Partner Violence: Assessing Feasibility of
      a Collaborative Model.
AB  - Despite the known consequences associated with children's exposure to intimate
      partner violence (IPV), numerous children exposed to IPV never access victim
      services and/or mental health treatment. Informed by the Child Development
      Community Policing Program (CD-CP), the Child Trauma Response Team (CTRT) is
      designed to provide a coordinated, immediate, trauma-informed, and
      interdisciplinary response to children, adolescents, and their impacted family
      members who are exposed to severe IPV. The aim of this study was to explore the
      feasibility of the CTRT from the perspective of the key stakeholders and to
      identify what facilitated and/or hindered the collaborative model. Interviews
      were conducted with all 12 CTRT stakeholders of whom three worked for law
      enforcement, four worked for the district attorney's office, four worked for the
      nonprofit victim service organization, and one worked for the city office funding
      the pilot. Results indicated that the CTRT program evolved through a cyclical
      process including (a) implementing and enhancing program services, (b) defining
      and nurturing partner relationships, and (c) shifting practices among partnering
      agencies. The results provide concrete tools and practices that were successful
      in the CTRT pilot implementation. Despite the potential barriers to successful
      multidisciplinary collaborations, it is critical that we invest in developing and
      implementing collaborative intervention models in the IPV field. The CTRT model
      is an innovative model that conducts multidisciplinary coordinated outreach to
      families experiencing severe IPV to enhance family engagement in services and,
      when appropriate, in the criminal justice process.

PMID- 29642771
TI  - Restoration of Peripheral Intermediate and Classical Monocytes Expressing HLA-DR
      in Patients With Lung Adenocarcinoma After Platinum-Based Chemotherapy.
AB  - Lung adenocarcinoma represents one of the lung cancer subtypes with major
      prevalence. Accumulating evidence indicates that the immune system plays an
      important role in the evolution of the neoplastic process; additionally, several
      reports suggest that chemotherapy has an immunomodulatory effect. In order to
      identify the peripheral subpopulations of leukocytes that may change after
      chemotherapy, we evaluated several peripheral immune subpopulations of monocytes
      and lymphocytes by multicolor flow cytometry. In addition, we also measured
      cytokines and growth factors on plasma in order to evaluate the pro-inflammatory
      context in patients with lung adenocarcinoma after chemotherapy. We found that
      HLA-DR+ classical and intermediate monocytes were decreased in patients before
      chemotherapy, compared to controls. After chemotherapy, the relative percentage
      of those subpopulations was restored. In addition, interleukin 1beta, interleukin
      12, and interleukin 5 were increased after chemotherapy compared to
      prechemotherapy levels, while MIP-1beta was decreased.

PMID- 29642772
TI  - The Assessment of Clinical Usage and Prognostic Value of YKL-40 Serum Levels in
      Patients With Rectal Cancer Without Distant Metastasis.
AB  - BACKGROUND: Colorectal cancer is one of the most common and significant
      malignancies in the world. YKL-40 (chitinase-3-like protein 1) is involved in
      cell proliferation, migration, inflammation, and tissue remodeling; and serum
      levels of YKL-40 are associated with patient outcome in various cancers. The aim
      of this study was to assess the potential clinical usage of YKL-40 pretreatment
      serum levels as a prognostic biomarker in rectal cancer. METHODS: Concentrations
      of YKL-40 and standard tumor marker-Carcinoembryonic antigen (CEA)-were assessed
      in serum of 83 patients with rectal cancer without distant metastasis, and
      association with clinicopathological characteristics and disease-free and overall
      survival was evaluated. RESULTS: Concentration of YKL-40 was significantly higher
      in serum of patients with rectal cancer compared to healthy controls ( P =
      .0001), and YKL-40 levels were able to predict rectal cancer (area under the
      Receiver Operating Characteristic [ROC] curve = .769) with higher accuracy than
      CEA (area under the ROC curve = .728) in patients with early stage disease.
      Increased YKL-40 levels were significantly associated with age ( P = .001);
      however, no association with other clinicopathological characteristics was
      observed. Finally, in patients with recurrence, the percentage of cases with
      increased concentration of YKL-40 was significantly higher than in patients
      without recurrence ( P = .041), and Kaplan-Meier analysis demonstrated that
      elevated YKL-40 concentration is a predictor of poor overall survival in patients
      with rectal cancer. CONCLUSION: Pretreatment serum levels of YKL-40 may be a
      novel prognostic factor of overall and disease-free survival in patients with
      nonmetastatic colorectal cancer.

PMID- 29642774
TI  - Understanding Sorority Women's Privacy Management About Condom Use.
AB  - Sorority women are at risk for engaging in unsafe sexual behavior. Fortunately,
      the positive influence of peer communication about condom use can mitigate the
      risk these women face. To better understand this communication, this article
      investigates sorority women's communication about condom use through focus
      groups, using the lens of the theory of Communication Privacy Management. The
      results revealed the criteria for privacy rules sorority women use to negotiate
      privacy and engage in comfortable communication with other women in the sorority.
      The analysis also revealed an external privacy boundary; the women sought to
      maintain a good reputation for their social group, and followed explicit and
      implicit privacy management rules to do so. The implications for this study
      include better understanding of the personal and collective boundaries of privacy
      management, and improvements in sorority and college student sexual health
      programs.

PMID- 29642773
TI  - DCE-MRI-Derived Volume Transfer Constant (Ktrans) and DWI Apparent Diffusion
      Coefficient as Predictive Markers of Short- and Long-Term Efficacy of
      Chemoradiotherapy in Patients With Esophageal Cancer.
AB  - This study aimed to evaluate both the short- and long-term efficacies of
      chemoradiotherapy in relation to the treatment of esophageal cancer . This was
      achieved through the use of dynamic contrast-enhanced magnetic resonance imaging
      derived volume transfer constant and diffusion weighted imaging-derived apparent
      diffusion coefficient . Patients with esophageal cancer were assigned into the
      sensitive and resistant groups based on respective efficacies in
      chemoradiotherapy. Dynamic contrast-enhanced magnetic resonance imaging and
      diffusion weighted imaging were used to measure volume transfer constant and
      apparent diffusion coefficient, while computed tomography was used to calculate
      tumor size reduction rate. Pearson correlation analyses were conducted to analyze
      correlation between volume transfer constant, apparent diffusion coefficient, and
      the tumor size reduction rate. Receiver operating characteristic curve was
      constructed to analyze the short-term efficacy of volume transfer constant and
      apparent diffusion coefficient, while Kaplan-Meier curve was employed for
      survival rate analysis. Cox proportional hazard model was used for the risk
      factors for prognosis of patients with esophageal cancer. Our results indicated
      reduced levels of volume transfer constant, while increased levels were observed
      in ADCmin, ADCmean, and ADCmax following chemoradiotherapy. A negative
      correlation was determined between ADCmin, ADCmean, and ADCmax, as well as in the
      tumor size reduction rate prior to chemoradiotherapy, whereas a positive
      correlation was uncovered postchemoradiotherapy. Volume transfer constant was
      positively correlated with tumor size reduction rate both before and after
      chemoradiotherapy. The 5-year survival rate of patients with esophageal cancer
      having high ADCmin, ADCmean, and ADCmax and volume transfer constant before
      chemoradiotherapy was greater than those with respectively lower values.
      According to the Cox proportional hazard model, ADCmean, clinical stage, degree
      of differentiation, and tumor stage were all confirmed as being independent risk
      factors in regard to the prognosis of patients with EC. The findings of this
      study provide evidence suggesting that volume transfer constant and apparent
      diffusion coefficient as being tools allowing for the evaluation of both the
      short- and long-term efficacies of chemoradiotherapy esophageal cancer treatment.

PMID- 29642775
TI  - (Dis-)solving the Weight Problem in Binge-Eating Disorder: Systemic Insights From
      Three Treatment Contexts With Weight Stability, Weight Loss, and Weight
      Acceptance.
AB  - Binge-eating disorder (BED) is a severe eating disorder strongly associated with
      obesity. Treatments struggle to provide safe and effective ways of addressing
      weight in a BED context. This study explored a two-phased treatment for BED
      developed at a major out-patient eating disorder service in Denmark. The study
      used interviews and participant observations to gain insight into experiences and
      processes related to weight and body issues in three treatment contexts that
      addressed weight stability, weight acceptance, and weight loss. Using systems
      theory, the study proposed a relational weight problem that embeds feelings of
      non-acceptance due to weight, a merge of weight and identity, and an internalized
      body- and weight-critical gaze of others. Contrary to critical claims that weight
      acceptance discourages people with obesity from engaging in weight loss efforts,
      this study suggests that acceptance and a disentanglement of weight and identity
      are prerequisites for weight loss for this group.

PMID- 29642776
TI  - The Pink Underside: The Commercialization of Medical Risk Assessment and Decision
      Making Tools for Hereditary Breast Cancer Risk.
AB  - The growth of the Internet since the millennium has opened up a myriad of
      opportunities for education, particularly in medicine. Although those looking for
      health care information used to have to turn to a face-to-face doctor's visit, an
      immense library of medical advice is now available at their fingertips. The BRCA
      genetic predispositions (mutations of the BRCA1 and BRCA2 breast cancer genes)
      which expose men and women to greater risk of breast, ovarian, and other cancers
      can be researched extensively online. Several nonprofit organizations now offer
      online risk assessment and decision-making tools meant to supplement conversation
      with medical professionals, which in actuality are quickly replacing it. We argue
      here through a critical qualitative template analysis of several such tools that
      the discursive frameworks utilized are prone to fearmongering, commercialization,
      and questionable validity. Left unchecked, these assessment tools could do more
      harm than good in driving young women especially to take unnecessary extreme
      surgical action.

PMID- 29642777
TI  - Parental Experiences of Child Participation in a Phase I Pediatric Oncology
      Clinical Trial: "We Don't Have Time to Waste".
AB  - Children with cancer are only eligible for phase I clinical trials (P1Ts) when no
      known curative therapy remains. However, the primary aims of P1Ts are not focused
      on directly benefiting participants. This raises ethical concerns that can be
      best evaluated by exploring the experiences of participants. An empirical
      phenomenology study, using an adapted Colaizzi method, was conducted of 11
      parents' lived experiences of their child's participation in a pediatric oncology
      P1T. Study findings were that parents' experiences reflected what it meant to
      have a child fighting to survive high-risk cancer. Although elements specific to
      P1T participation were identified, more pervasive was parents' sense of running
      out of time to find an effective treatment and needing to use time they had with
      their child well. Even though some problems were identified, overall parents did
      not regret their child's P1T participation and would recommend P1Ts to other
      parents of children with cancer.

PMID- 29642778
TI  - Effects of psycho-education plus basic cognitive behavioural therapy strategies
      on medication-treated adolescents with depressive disorder in Nigeria.
AB  - OBJECTIVE: Limited data exists on psychological interventions for adolescent
      depression in African countries such as Nigeria. This study therefore
      investigates the effects of a psychological intervention that includes psycho
      education and basic elements of cognitive behavioural therapy (CBT) on depressed
      medication-treated adolescents in Nigeria. METHODOLOGY: This was a pre-post one
      group intervention study of 18 adolescents aged 13-18 years with clinically
      diagnosed depressive disorder, attending a specialist psychiatric hospital. They
      had been on antidepressants for 3 months or longer. Depressive symptoms,
      knowledge of depression, hope, and attitudes towards treatment adherence were
      measured at baseline and repeated at 1 and 4 weeks post-intervention. The
      adolescents received four sessions of a group-based manualised intervention
      focused on psycho-education and basic CBT strategies. RESULTS: Statistically
      significant reductions in depressive symptoms were recorded, as were improvements
      in the adolescents' knowledge of depression, hope, and attitude towards treatment
      adherence one week after the intervention (all p = 0.001). All differences were
      sustained at 4 weeks post-intervention. Participants' satisfaction with the
      intervention was high. CONCLUSION: This study suggests that adding psycho
      education with elements of CBT to antidepressant treatment is feasible,
      acceptable and can produce further benefits to depressed adolescents in this
      region.

PMID- 29642779
TI  - Analyzing the Commitment of College Students Using a Brief, Contextualized
      Measure of Need Satisfaction From the Perspective of Self-Determination Theory.
AB  - This study empirically confirmed the relationships between the degree to which
      students satisfied three basic needs (competence, relatedness, and autonomy) and
      the strength of their commitments to the university they attended and to
      obtaining a baccalaureate degree. A questionnaire was administered online to 1257
      students at two 4-year universities. Regression analysis yielded statistically
      significant associations between the three needs and Institutional Commitment and
      Degree Commitment, explaining more than 20% of the variance in the latter two
      variables.

PMID- 29642780
TI  - Validating Translation Test Items via the Many-Facet Rasch Model.
AB  - This study applied the many-facet Rasch model to assess learners' translation
      ability in an English as a foreign language context. Few attempts have been made
      in extant research to detect and calibrate rater severity in the domain of
      translation testing. To fill the research gap, this study documented the process
      of validating a test of Chinese-to-English sentence translation and modeled
      raters' scoring propensity defined by harshness or leniency, expert/novice
      effects on severity, and concomitant effects on item difficulty. Two hundred
      twenty-five, third-year senior high school Taiwanese students and six educators
      from tertiary and secondary educational institutions served as participants. The
      students' mean age was 17.80 years ( SD = 1.20, range 17-19). The exam consisted
      of 10 translation items adapted from two entrance exam tests. The results showed
      that this subjectively scored performance assessment exhibited robust
      unidimensionality, thus reliably measuring translation ability free from
      unmodeled disturbances. Furthermore, discrepancies in ratings between novice and
      expert raters were also identified and modeled by the many-facet Rasch model. The
      implications for applying the many-facet Rasch model in translation tests at the
      tertiary level were discussed.

PMID- 29642781
TI  - Differential coactivation in a redundant signals task with weak and strong go/no
      go stimuli.
AB  - When participants respond to stimuli of two sources, response times (RTs) are
      often faster when both stimuli are presented together relative to the RTs
      obtained when presented separately (redundant signals effect [RSE]). Race models
      and coactivation models can explain the RSE. In race models, separate channels
      process the two stimulus components, and the faster processing time determines
      the overall RT. In audiovisual experiments, the RSE is often higher than
      predicted by race models, and coactivation models have been proposed that assume
      integrated processing of the two stimuli. Where does coactivation occur? We
      implemented a go/no-go task with randomly intermixed weak and strong auditory,
      visual, and audiovisual stimuli. In one experimental session, participants had to
      respond to strong stimuli and withhold their response to weak stimuli. In the
      other session, these roles were reversed. Interestingly, coactivation was only
      observed in the experimental session in which participants had to respond to
      strong stimuli. If weak stimuli served as targets, results were widely consistent
      with the race model prediction. The pattern of results contradicts the inverse
      effectiveness law. We present two models that explain the result in terms of
      absolute and relative thresholds.

PMID- 29642782
TI  - The role of retrieval practice in memory and analogical problem-solving.
AB  - Retrieval practice (e.g., testing) has been shown to facilitate long-term
      retention of information. In two experiments, we examine whether retrieval
      practice also facilitates use of the practised information when it is needed to
      solve analogous problems. When retrieval practice was not limited to the
      information most relevant to the problems (Experiment 1), it improved memory for
      the information a week later compared with copying or rereading the information,
      although we found no evidence that it improved participants' ability to apply the
      information to the problems. In contrast, when retrieval practice was limited to
      only the information most relevant to the problems (Experiment 2), we found that
      retrieval practice enhanced memory for the critical information, the ability to
      identify the schematic similarities between the two sources of information, and
      the ability to apply that information to solve an analogous problem after a hint
      was given to do so. These results suggest that retrieval practice, through its
      effect on memory, can facilitate application of information to solve novel
      problems but has minimal effects on spontaneous realisation that the information
      is relevant.

PMID- 29642783
TI  - The interplay of crossmodal attentional preparation and modality compatibility in
      cued task switching.
AB  - Two experiments examined the influence of preparation on modality compatibility
      effects in task switching. The term modality compatibility refers to the
      similarity between the stimulus modality and the modality of response-related
      sensory consequences. Previous research showed evidence for modality
      compatibility benefits in task switching when participants switched either
      between two modality compatible tasks (auditory-vocal and visual-manual) or
      between two modality incompatible tasks (auditory-manual and visual-vocal). In
      this study, we investigated the influence of active preparation on modality
      compatibility effects in task switching. To this end, in Experiment 1, we
      introduced unimodal modality cues, whereas in Experiment 2, bimodal abstract cues
      were used. In both experiments, the cue-stimulus interval (CSI) was manipulated
      while holding the response-stimulus interval (RSI) constant. In both experiments,
      we found not only decreased switch costs with long CSI but also the elimination
      of the residual switch costs. More importantly, this preparation effect did not
      modulate the modality compatibility effect in task switching. To account for this
      data pattern, we assume that cue-based preparation of switches by modality
      mappings was highly effective and produced no residual reaction time (RT) costs
      with long CSI.

PMID- 29642784
TI  - The interaction of notional number and morphophonology in subject-verb agreement:
      A role for working memory.
AB  - Research shows that cross-linguistically, subject-verb agreement with complex
      noun phrases (e.g., The label on the bottles) is influenced by notional number
      and the presence of homophony in case, gender, or number morphology. Less well
      understood is whether notional number and morphophonology interact during speech
      production, and whether the relative impact of these two factors is influenced by
      working memory capacity. Using an auditory sentence completion task, we
      investigated the impact of notional number and morphophonology on agreement with
      complex subject noun phrases in Dutch. Results revealed main effects of notional
      number and morphophonology. Critically, there was also an interaction between
      morphophonology and notional number because participants showed greater notional
      effects when the determiners were homophonous and morphophonologically ambiguous.
      Furthermore, participants with higher working memory scores made fewer agreement
      errors when the subject noun phrase contained homophonous determiners, and this
      effect was greater when the subject noun phrase was notionally singular. These
      findings support the hypothesis that cue-based retrieval plays a role in
      agreement production, and suggests that the ability to correctly assign subject
      verb agreement-especially in the presence of homophonous determiners-is modulated
      by working memory capacity.

PMID- 29642785
TI  - Moral fatigue: The effects of cognitive fatigue on moral reasoning.
AB  - We report two experiments that show a moral fatigue effect: participants who are
      fatigued after they have carried out a tiring cognitive task make different moral
      judgements compared to participants who are not fatigued. Fatigued participants
      tend to judge that a moral violation is less permissible even though it would
      have a beneficial effect, such as killing one person to save the lives of five
      others. The moral fatigue effect occurs when people make a judgement that focuses
      on the harmful action, killing one person, but not when they make a judgement
      that focuses on the beneficial outcome, saving the lives of others, as shown in
      Experiment 1 ( n = 196). It also occurs for judgements about morally good
      actions, such as jumping onto railway tracks to save a person who has fallen
      there, as shown in Experiment 2 ( n = 187). The results have implications for
      alternative explanations of moral reasoning.

PMID- 29642786
TI  - ?

PMID- 29642787
TI  - ?

PMID- 29642788
TI  - ?

PMID- 29642789
TI  - ?

PMID- 29642790
TI  - ?

PMID- 29642791
TI  - [CME: Cavitary Pulmonary Disease - Differential Diagnosis and Diagnostic Work
      Up].

PMID- 29642792
TI  - ?

PMID- 29642793
TI  - A Clinical Patient Reporting Tool: Giving ADPKD Patients Back Their Data.

PMID- 29642794
TI  - ?

PMID- 29642797
TI  - Recurrent Aortic Dissection in a Patient With an Actin Mutation Treated With a
      Laser-Fenestrated Aortic Arch Stent-Graft.
AB  - A 58-year-old African American female, who had previously undergone a valve
      sparing aortic root replacement for a type A dissection, represented 2 months
      later with a new focal dissection and aneurysm with intramural hematoma just
      distal to the origin of the left subclavian artery. Since no landing zone distal
      to the subclavian artery existed, the patient underwent thoracic endovascular
      aortic repair with laser fenestration-aided stent-graft placement in the left
      subclavian artery. The patient recovered without complication, and 52 months
      later, she is doing well with normal renal function and ambulatory status.

PMID- 29642795
TI  - Recommendations of Swiss Memory Clinics for the Diagnosis of Dementia
AB  - The early diagnosis of subjectively perceived or externally anamnestically
      observed cognitive impairments is essentialfor proving neurodegenerative diseases
      or excluding treatable causes such as internal, neurological or
      psychiatricdisorders. Only in this way is early treatment made possible. As part
      of the project 3.1 of the National Dementia Strategy2014-2019 ("Development and
      expansion of regional and networked centres of competence for diagnostics"), the
      associationSwiss Memory Clinics (SMC) set itself the goal of developing quality
      standards for dementia clarification and improvingthe community-based care in
      this field. In these recommendations, general guidelines of diagnostics and
      individualexamination possibilities are presented, and standards for the related
      processes are suggested. Individual areas such asanamnesis, clinical examination,
      laboratory examination, neuropsychological testing and neuroradiological
      procedures arediscussed in detail as part of standard diagnostics, and
      supplementary examination methods for differential diagnosisconsiderations are
      portrayed. The most important goals of the SMC recommendations for the diagnosis
      of dementia are togive all those affected access to high-quality diagnostics, if
      possible, to improve early diagnosis of dementia and to offerthe basic service
      providers and the employees of Memory Clinics a useful instrument for the
      clarification.

PMID- 29642798
TI  - A retrospective study of a new n-butyl-2-cyanoacrylate glue ablation catheter
      incorporated with application guiding light for the treatment of venous
      insufficiency: Twelve-month results.
AB  - Objective This study aims to present the early results of a retrospective study
      of the use of novel n-butyl-2-cyanoacrylate (VenaBlock)-based nontumescent
      endovenous ablation with a guiding light for the treatment of patients with
      varicose veins. Methods Patients with lower limb venous insufficiency were
      treated with n-butyl-2-cyanoacrylate (VenaBlock Venous Closure System) between
      April 2016 and July 2016. The study enrolled adults aged 21-70 years with
      symptomatic moderate to severe varicosities (C2-C4b) and great saphenous vein
      reflux lasting longer than 0.5 s with great saphenous vein diameter between 5.5
      and 15 mm assessed in the standing position. No compression stockings were used
      after the procedure. Duplex ultrasound imaging and clinical follow-up were
      performed on the third day, first month, sixth month, and 12th month. Clinical,
      etiological, anatomical, pathophysiological classification; venous clinical
      severity score; and completed Aberdeen varicose vein questionnaire were recorded.
      Results Five hundred thirty-eight patients with great saphenous vein incompetency
      underwent n-butyl-2-cyanoacrylate ablation. The mean ablation length was 25.69 +/
      4.8 cm, and the average amount of n-butyl-2-cyanoacrylate delivered was 0.87 +/-
      0.15 ml. The mean procedure time was 11.7 +/- 4.9 min. Procedural success was
      100%, and complete occlusion was observed after treatment and at the third-day
      follow-up. We observed ecchymosis in five patients (1.00%) at the entry site at
      the third-day follow-up. Phlebitis was encountered with six (1.20%) patients. No
      skin pigmentation, hematoma, paresthesia, deep vein thrombosis, or pulmonary
      embolism was observed. Kaplan-Meier analysis yielded an occlusion rate of 99.4%
      at the 12-month follow-up. All patients had significant improvement in venous
      clinical severity score and Aberdeen varicose vein questionnaire scores
      postoperatively ( p <0.0001). Venous clinical severity score scores decreased
      from 5.43 +/- 0.87 to 0.6 +/- 0.75. Aberdeen varicose vein questionnaire scores
      decreased from 18.32 +/- 5.24 to 4.61 +/- 1.42. Conclusions The procedure appears
      to be feasible, safe, and efficient in treating the great majority of incompetent
      great saphenous veins with this technique.

PMID- 29642799
TI  - Placental Defects: An Epigenetic Perspective.
AB  - Placenta, the first organ to be formed during gestation, plays a crucial role in
      intrauterine regulation of fetal growth and is involved in several functions
      during fetal development such as exchange of nutrients, wastes, and gases;
      protection against maternal immune rejection; and various metabolic and endocrine
      functions. Several studies have shown the regulation of epigenetic factors and
      the phenomenon of genomic imprinting in placentation and embryogenesis. Any gain
      or loss of imprint marks in the placenta has been shown to associate with severe
      placental defects which in turn affect both the mother and the growing fetus and
      can have long-term effects during adulthood. Using candidate and genome-wide high
      throughput approaches, several studies have shown association between aberrant
      epigenetic factors in the form of DNA methylation, histone modifications, and non
      coding RNAs and placental defects in both human and animal models as well as
      using in vitro studies. In the current review, we discuss several placenta
      related pathophysiologies and their association with various aberrant epigenetic
      factors and gene expression patterns in both in vivo and in vitro systems. This
      review will help the researchers gain insight into the recent evidences in the
      area of placentation and epigenetics and to design novel strategies to study and
      prevent the defects in this underestimated organ.

PMID- 29642800
TI  - The Usefulness of CD34, PCNA Immunoreactivity, and Histopathological Findings for
      Prediction of Pain Persistence After the Removal of Endometrioma.
AB  - Endometriosis is an estrogen-dependent inflammatory disease that causes
      infertility and chronic pelvic pain. Ovarian endometrioma is the most common form
      of endometriosis, and conservative surgery is the main preferred therapeutic
      approach for endometrioma-associated symptoms. The aim of this study was to
      investigate the persistence of cyclic and noncyclic pelvic pain (NCPP) after
      endometrioma excision and their relationship to clinical and histopathological
      findings. In this prospective observational study, 41 symptomatic patients were
      evaluated for the presence of pain symptoms 3 to 6 months after endometrioma
      excision. Tissue specimens of endometrioma were collected during the operation
      and embedded in paraffin. The persistence of pain was 41.4%. Surgical excision of
      endometrioma significantly decreased NCPP and dysmenorrhea, but not dyspareunia (
      P < .0001, P = .0001, and P = .25, respectively). Histopathological changes,
      including depth of endometriosis penetration into the cyst wall, the presence of
      macrophage infiltration, and vascularity of endometrioma cyst walls were
      significantly higher in patients with pain persistence than in patients without
      pain persistence ( P = .0034, P = .0042, and P = .0007, respectively). Moreover,
      proliferating cell nuclear antigen (PCNA) and CD34 immunoreactivity in both
      glandular and stromal cells and vascular endothelium were significantly higher in
      patients with pain persistence ( P = .0079 and P = .0025, respectively).
      Additionally, these histopathological changes and PCNA and CD34 immunoreactivity
      were significantly correlated with the persistence of NCPP and dysmenorrhea. The
      discovered differences in patients with endometrioma with or without pain
      persistence may indicate a possible relationship between endometrioma-associated
      pain and histopathological variability of endometrioma.

PMID- 29642801
TI  - Regulation of Cell Cycle Regulatory Proteins by MicroRNAs in Uterine Leiomyoma.
AB  - The objective of this study was to determine whether miR-93, miR-29c, and miR
      200c, which we previously reported to be downregulated in leiomyomas, target cell
      cycle regulatory proteins that influence cell proliferation. Based on TargetScan
      algorithm 3 cell cycle regulatory proteins namely, E2F transcription factor 1
      (E2F1), Cyclin D1 (CCND1) and CDK2 which were predicted to be targets of these
      miRNAs were  further analyzed. In 30 hysterectomy specimens, we found the
      expression of E2F1 and CCND1 messenger RNA (mRNA) was increased in leiomyoma as
      compared to matched myometrium, with no significant changes in CDK2 mRNA levels.
      There was a significant increase in the abundance of all 3 proteins in leiomyoma
      in comparison with matched myometrium. Using luciferase reporter assay, we
      demonstrated E2F1 and CCND1 are targets of miR-93 and CDK2 is a target of miR-29c
      and miR-200c. We confirmed these findings through transfection studies in which
      transfection of primary leiomyoma cells with miR-93 resulted in a significant
      decrease in the expression of E2F1 and CCND1 mRNA and protein levels, whereas
      knockdown of miR-93 had the opposite effect. Similarly, overexpression of miR-29c
      and miR-200c in leiomyoma cells inhibited the expression of CDK2 protein and
      mRNA, whereas knockdown of this microRNAs (miRNA) had the opposite effect.
      Transfection of miR-29c, miR-200c, and miR-93 in primary leiomyoma cells resulted
      in a time-dependent inhibition of cell proliferation and cell motility. These
      results collectively indicate that the 3 miRNAs known to be downregulated in
      fibroid tumors are critical in regulation of cell proliferation because of their
      effects on 3 key cell cycle regulatory proteins, which are overexpressed in
      uterine leiomyomas.

PMID- 29642802
TI  - Effect of High-Fat Diet on Immature Female Mice and Messenger and Noncoding RNA
      Expression Profiling in Ovary and White Adipose Tissue.
AB  - Obesity is a chronic multifactorial disease prevalent in many areas of the world
      and is a major cause of morbidity and mortality. In women, obesity increases the
      risks of both metabolic and reproductive diseases, such as diabetes and
      infertility. The mechanisms underlying these effects, especially in young women,
      are largely unknown. To explore these mechanisms, we established a high-fat diet
      (HFD) model of obesity in immature female mice. Microarray analysis of gene
      expression in ovaries and white adipose tissue identified a large number of
      differentially expressed genes (>1.3-fold change) in both tissues. In ovaries of
      the HFD group, there were 208 differentially expressed messenger RNAs (mRNAs),
      including 98 upregulated and 110 downregulated, and 295 differentially expressed
      lncRNAs (long non coding RNAs), including 63 upregulated and 232 downregulated.
      In white adipose tissue, there were 625 differentially expressed mRNAs, including
      220 upregulated and 605 downregulated in the HFD group, and 1595 differentially
      expressed lncRNAs, including 1320 and 275 downregulated in the HFD group. Our
      results reveal significant differences between the transcriptomes of the HFD and
      control groups in both ovaries and white adipose tissue that provide clues to the
      molecular mechanisms of diet-induced female reproductive dysfunction and
      metabolic disorders, as well as biomarkers of risk for these disorders.

PMID- 29642803
TI  - Expression of N-Acetylglucosaminyltransferase III Promotes Trophoblast Invasion
      and Migration in Early Human Placenta.
AB  - INTRODUCTION: Trophoblast migration and invasion at the maternal-fetal interface
      are crucial events for normal placentation and successful pregnancy. This
      progress is well controlled by many placenta-specific factors. Inadequate
      trophoblast invasion results in poor placenta plantation or even complications
      such as preeclampsia. It has been shown that N-acetylglucosaminyltransferase III
      (GnT-III) participates in tumor invasion and metastasis as a suppressor; however,
      the expression of GnT-III and its role in normal pregnancy is unclear. Our
      objective was to characterize GnT-III expression and function during placental
      development and identify the underlying mechanisms. METHODS: The expression of
      GnT-III in human placental tissue from the first trimester was determined by
      immunohistochemistry. The HTR8/SVneo cell line was used to investigate the
      effects of GnT-III on proliferation, apoptosis, migration/invasion, matrix
      metalloproteinase (MMP) 2/9 activity, and the expression of the tissue inhibitor
      of metalloproteinase (TIMP) 1/2 using cell 3-[4,5-dimethylthiazol-2-yl]-2,5
      diphenyltetrazolium bromide assays, flow cytometric analysis, transwell
      migration/invasion assays, gelatin zymography, and Western blot, respectively.
      Moreover, a placental villous explant model was employed to determine its
      functions in placentation. RESULTS: In the first-trimester placental tissue, GnT
      III was localized within the cytotrophoblast, the syncytiotrophoblast and the
      trophoblast columns of human placental villi, decidual cells, and some
      extravillous cells in the maternal decidua. GnT-III silencing significantly
      inhibited HTR8/SVneo cell invasion and migration as well as extravillous explant
      outgrowth. The application of GnT-III siRNA significantly attenuated MMP2/9
      activity and increased TIMP1/2 expression. DISCUSSION AND CONCLUSION: GnT-III is
      expressed in trophoblasts during normal human pregnancy and is involved in
      regulating trophoblast function.

PMID- 29642804
TI  - Angioedema in Australia: hospital admission rates and fatalities, 2000-2013.

PMID- 29642806
TI  - Developing a sustainable health care system: the United Kingdom experience.

PMID- 29642807
TI  - The <em>Lancet</em> Countdown down under: tracking progress on health and climate
      change in Australia.

PMID- 29642809
TI  - A severe case of <em>Mycobacterium ulcerans</em> (Buruli ulcer) osteomyelitis
      requiring a below-knee amputation.

PMID- 29642808
TI  - Tackling the worsening epidemic of Buruli ulcer in Australia in an information
      void: time for an urgent scientific response.

PMID- 29642810
TI  - Preparing medical graduates for the health effects of climate change: an
      Australasian collaboration.

PMID- 29642811
TI  - Invisible injuries: patient harms we hear about when we take the time to ask.

PMID- 29642812
TI  - Striving for more socially just global health.

PMID- 29642813
TI  - the five cardinal signs of inflammation.

PMID- 29642814
TI  - Planetary health: what is it and what should doctors do?

PMID- 29642815
TI  - Pollution, climate change, and childhood asthma in Australia.

PMID- 29642816
TI  - Damp housing, gas stoves, and the burden of childhood asthma in Australia.
AB  - OBJECTIVE: To determine the proportion of the national childhood asthma burden
      associated with exposure to dampness and gas stoves in Australian homes. DESIGN:
      Comparative risk assessment modelling study. Setting, participants: Australian
      children aged 14 years or less, 2011. MAIN OUTCOME MEASURES: The population
      attributable fractions (PAFs) and number of disability-adjusted life years
      (DALYs) for childhood asthma associated with exposure to damp housing and gas
      stoves. RESULTS: 26.1% of Australian homes have dampness problems and 38.2% have
      natural gas as the main energy source for cooktop stoves. The PAF for childhood
      asthma attributable to damp housing was 7.9% (95% CI, 3.2-12.6%), causing 1760
      disability-adjusted life years (DALYs; 95% CI, 416-3104 DALYs), or 42 DALYs/100
      000 children. The PAF associated with gas stoves was 12.3% (95% CI, 8.9-15.8%),
      corresponding to 2756 DALYs (95% CI, 1271-4242), or 67 DALYs/100 000 children. If
      all homes with gas stoves were fitted with high efficiency range hoods to vent
      gas combustion products outdoors, the PAF and burden estimates were reduced to
      3.4% (95% CI, 2.2-4.6%) and 761 DALYs (95% CI, 322-1199). CONCLUSIONS: Exposure
      to damp housing and gas stoves is common in Australia, and is associated with a
      considerable proportion of the childhood asthma burden. Strategies for reducing
      exposure to indoor dampness and gas combustion products should be communicated to
      parents of children with or at risk of asthma.

PMID- 29642817
TI  - Rheumatic heart disease in Timor-Leste school students: an echocardiography-based
      prevalence study.
AB  - OBJECTIVES: To determine the prevalence of rheumatic heart disease (RHD) in
      school-aged children and young people in Timor-Leste. DESIGN: Prospective cross
      sectional survey. Echocardiography was performed by Australian cardiologists to
      determine the presence of RHD. Demographic data were also collected. Patients in
      whom RHD was detected were entered into a register to allow monitoring of
      adherence to secondary prophylaxis; the first dose of benzathine penicillin G
      (BPG) was administered on the day of screening. SETTING: Schools in urban (Dili)
      and rural (Ermera) Timor-Leste. PARTICIPANTS: School students aged 5-20 years.
      OUTCOME MEASURES: Definite and borderline RHD, as defined by World Heart
      Federation echocardiographic criteria. RESULTS: 1365 participants were screened;
      their median age was 11 years (IQR, 9-14 years), and 53% were girls. The
      estimated prevalence of definite RHD was 18.3 cases per 1000 population (95% CI,
      12.3-27.0 per 1000), and of definite or borderline RHD 35.2 per 1000 (95% CI,
      26.5-46.4 per 1000). Definite (adjusted odds ratio [aOR], 3.5; 95% CI, 1.3-9.4)
      and definite or borderline RHD (aOR, 2.7; 95% CI, 1.4-5.2) were more prevalent
      among girls than boys. Eleven children (0.8%) had congenital heart disease. Of
      the 25 children in whom definite RHD was identified, 21 (84%) received education
      and a first dose of BPG on the day of screening; all 25 have since received
      education about primary care for RHD and have commenced penicillin prophylaxis.
      CONCLUSIONS: The rates of RHD in Timor-Leste are among the highest in the world,
      and prevalence is higher among girls than boys. Community engagement is essential
      for ensuring follow-up and the effective delivery of secondary prophylaxis.

PMID- 29642818
TI  - Health burden associated with fire smoke in Sydney, 2001-2013.

PMID- 29642819
TI  - Tick-induced allergies: mammalian meat allergy and tick anaphylaxis.
AB  - Mammalian meat allergy after tick bites and tick anaphylaxis are the most serious
      tick-induced allergies. They are often severe, should be largely avoidable and
      offer fascinating insights into the development and prevention of allergies.
      Australian clinicians reported the first cases of tick anaphylaxis and discovered
      the association between tick bites and the development of mammalian meat allergy.
      The subsequent finding of the allergen epitope within the meat responsible for
      the allergic reaction, alpha-gal (galactose-alpha-1,3-galactose), stimulated
      further interest in this emergent allergy. Reports of mammalian meat allergy
      associated with bites from several tick species have now come from every
      continent where humans are bitten by ticks. The number of diagnosed patients has
      continued to rise. Clinically, mammalian meat allergy and tick anaphylaxis
      present quite differently. The prominent role of cofactors in triggering episodes
      of mammalian meat allergy can make its diagnosis difficult. Management of
      mammalian meat allergy is complicated by the manifold potential therapeutic
      implications due to the widespread distribution of the mammalian meat allergen,
      alpha-gal. Exposures to alpha-gal-containing medications have proved lethal in a
      minority of people, and fatal tick anaphylaxis has been reported in Australia.
      Prevention of tick bites is prudent and practicable; killing the tick in situ is
      crucial to both primary and secondary prevention of allergic reactions.
      Mechanisms in the development of mammalian meat allergy constitute a paradigm for
      how allergies might arise.

PMID- 29642820
TI  - Extreme heat threatens the health of Australians.

PMID- 29642821
TI  - Clinical quality registries for clinician-level reporting: strengths and
      limitations.

PMID- 29642823
TI  - Bringing relief to Rohingya refugees.

PMID- 29642822
TI  - Clinical quality registries for clinician-level reporting: strengths and
      limitations.

PMID- 29642824
TI  - Around the universities and research institutes.

PMID- 29642825
TI  - [Investigation of carbapenemase genes and molecular epidemiology of
      Enterobacteriaceae strains isolated between 2010-2014 in a university hospitals].
AB  - The worldwide spread of carbapenemase producing Enterobacteriaceae isolates has
      become a major threat of public health. This worrisome situation leads the
      development of new methods for carbapenemase screening, detection, prevention of
      spread and epidemiological data collection as mandatory. In this study, it was
      aimed to investigate existence and distribution of carbapenemase-encoding genes
      (CEGs) among carbapenem-resistant Enterobacteriaceae isolated from various
      clinical samples in Ankara University Faculty of Medicine, Ibni Sina Hospital,
      Central Microbiology Laboratory between June 2010-May 2014 and detect their
      clonal relationship. A total of 112 non-repetitive Enterobacteriaceae isolates
      which were intermediate or resistant to ertapenem were identified by using
      Phoenix (BD Diagnostic Systems, Sparks, USA) automated microbiology system. After
      DNA extraction from the isolates, 11 carbapenemase-encoding genes (CEGs) (blaIMP,
      blaVIM, blaSPM, blaKPC, blaNDM, blaOXA-48, blaGIM, blaSIM, blaAIM, blaDIM ve
      blaBIC) were detected with PCR. The clonal relationship among the isolates was
      determined by PFGE method following digestion with Xbal DNA macrorestriction
      endonuclease. Among 112 isolates Klebsiella pneumoniae was the most frequent (n=
      79, 70.5%) bacteria followed by Escherichia coli (n= 15, 13.4%), Enterobacter
      cloacae (n= 10, 8.9%), Enterobacter aerogenes (n= 4, 3.6%) and Klebsiella oxytoca
      (n= 4, 3.6%) respectively. blaOXA-48 was the most frequent gene detected. Among
      83 (74.1%) isolates blaOXA-48 was detected alone and in 7 (6.3%) of the isolates
      it was identified with blaVIM gene coexistence. blaVIM gene was identified as the
      second most frequent CEG among the isolates. blaVIM gene was detected positive in
      9 (8%) isolates. blaNDM gene was identified in 2 (1.8%) isolates. Ten of the
      K.pneumoniae isolates with identical PFGE pattern were named as pulsotype B.
      These isolates were found to be similar in terms of isolate location, isolation
      dates, antibiotic resistance patterns and the carbapenemase genes they carry, and
      are considered to be potential outbreak isolates originated from intensive care
      units. On the other hand CEGs were found in the clinical samples obtained from
      five out-patients suggesting that community-acquired infections may also arise
      due to carbapenemase producing Enterobacteriaceae in our country where blaOXA-48
      producers are endemic. According to this study, blaOXA-48 producing gram negative
      bacteria were frequent in our hospital. The prevalance of blaVIM gene among
      metallo-beta-lactamases and coexistence with blaOXA-48 gene was remarkable. The
      frequency of blaNDM producing isolates in our hospital was not detected as high
      yet. In this study, the identification of carbapenemase producing bacteria as
      outbreak strains in our hospital indicated that cross-sectional surveillance for
      carbapenemase-producing bacteria from each patient was valuable in terms of early
      diagnosis of outbreaks.

PMID- 29642826
TI  - [Investigation of high-risk ST131 clone in ESBL-producing Escherichia coli
      isolates isolated from urine and non-urinary clinical specimens with MALDI-TOF MS
      and real time PCR].
AB  - In recent years, the ST131 clone was identified as a high risk pandemic clone
      among Escherichia coli isolates by multilocus sequence typing (MLST) studies and
      has been associated with extended spectrum beta-lactamase (ESBL) production
      (often with CTX-M-15) and antibiotic resistance especially against
      fluoroquinolones. The aim of this study was to determine the rate of high risk
      ST131 clone in ESBL producing E.coli isolates in our region, to investigate the
      sensitivity of MALDI-TOF MS in the detection of ST131 clone, and to compare the
      frequency of antimicrobial resistance among ST131 and non-ST131 isolates. A total
      of 251 urinary and 50 non-urinary E.coli isolates identified in our hospital
      central laboratory between February 2016-February 2017 were included in the
      study. Real-time PCR and MALDI-TOF MS methods were used for the detection of
      E.coli ST131 clone. For the statistical evaluation of the rate of antibiotic
      resistance among isolates of ST131 and non-ST131 clones, chi-square test was
      used. p value under 0.05 was considered as significant. Of the 301 isolates, 110
      (36.6%) and 92 (30.6%) isolates were identified as ST131 clone by real-time PCR
      and MALDI-TOF MS, respectively. According to real-time PCR results, 91 (36.3%) of
      251 urinary isolates and 19 (38%) of 50 non-urinary isolates were found as ST131
      clone; there was no statistically significant difference between the groups.
      Ciprofloxacin resistance was found to be significantly higher in ST131 isolates
      than the non-ST131 isolates (78.2%, n= 86 vs. 53.4%, n= 102). No statistically
      significant difference was determined for the other antibiotics tested. For the
      detection of E.coli ST131 clone; sensitivity of MALDI-TOF MS was 84%, specificity
      was 100% while positive predictive value was 100% and negative predictive value
      was 92%. In conclusion, further investigation of the high risk E.coli ST131 clone
      in our country, in which ESBL ratios and antibiotic resistance rates, especially
      in fluoroquinolones, are high, is important for the development of new strategies
      to control antibiotic resistance. MALDI-TOF MS method is particularly useful for
      easy and fast detection of the high risk E.coli ST131 clone.

PMID- 29642827
TI  - [Analysis of hepatitis B virus (HBV) preS1, preS2 and S gene regions from patient
      groups infected with HBV genotype D].
AB  - Mutations in preS and S gene regions of hepatitis B virus genome may cause immune
      escape and diagnostic escape HBV mutants. The aim of this study was to determine
      preS1, preS2 and S gene regions of HBV from HBV infected patient groups by
      sequence analysis and contribute to the relevant literature. Nucleic acid
      sequence analysis of preS and S genes of HBV PCR products from 56 archived plasma
      samples sent to Ege University Faculty of Medicine Medical Microbiology
      Department Molecular Virology laboratory, for HBV tests were determined by chain
      termination reaction. Amino acid (aa) sequences were compared with the reference
      sequences obtained from GenBank. Plasma samples belonged to four groups of
      patients: A- Chronic HBV infected patients with typical HBV serological profiles
      (22 samples), B- HBV infected patients with atypical HBV serological profiles (26
      samples), C- HBV re-infected patients after liver transplantation (5 samples), D-
      Seroconversion phase following acute HBV infection (3 samples). One of two
      vaccine escape mutant samples was also diagnostic escape mutant; the other
      diagnostic escape mutant was isolated from anti-HBc positive sample. All of the
      sequences were determined as genotype D. HBsAg subtypes were determined as; two
      ayw1, six ayw3, two mix, 46 ayw2. Among the 304 codons analysed between preS 33rd
      and S 162nd amino acids; aa variants were determinedin 105 codons (34.5%).
      Sequences can be found in GenBank with accession numbers FJ001941-FJ001996. At
      least one aa variation was detected in 48 of 56 samples (85.7%). The amino acid
      variants were as follows; PreS1: A33T, A39T, P41K, D44del, D50N, T51P, D54N,
      L65P/M, F67L, W77T, A81S, Q82E, I84T, L85I/M, Q86H/T, L88S, A90T/V, N91K/del,
      A95P, S96A, T97I/A, N98K, Q100K, S101T, S109T, P110S, N114D/E, PreS2: M1V, Q2R,
      S5H, F8S, H9Q, Q13L, D14N, R16K, R18K, G19S/D, F22L/S, S28T, G30E, N33T, V39A,
      P41H/L, I42T/L, I45T, F46Y, S47L, R48K, I49T, D51V/G, P52L, A53V, L54R/G, N55K; S
      gene: E2D, I4F, F8L, G10A, V14A, F20S, L22del, R24K, P29L, Q30K, N40S, F41del,
      G44E, T45L, T46P, V47A, L49R, Q54R, P56L, S64F, P70A, M75I, C76Y, R79H, I81T,
      F83C, L88P, L94S, Y100F, Q101H/R, M103L, L104F, L109I/M, I110L, G112S/R, S113N/P,
      S114A/del, T115I, T116N, T118A/K, P120A/T, T123A, in "a" determinant; T126I,
      Q129H/R, T131N, M133T, Y134N, S136Y, S143L/M/T, D144E, G145A/R. Deletions were
      also found in all three preS/S gene regions. The highest number of aa variations
      were detectedin the isolated anti-HBc positive sample (in 24 codons), followed by
      liver transplant group (8-13 codons). Point mutation was detected in the preS2/S
      promoter CCAAT box. Major hydrophilic region (MHR) variants were determined in
      41.1% of 56 samples. The highest number of MHR variants belonged to atypical HBV
      serological profile group (group B; 61.5%) and liver transplantation group with
      HBV re-infection (all C group). Among the diagnostic escape and immune escape
      mutant (anti-HBs positive) samples, reported MHR and "a" determinant mutations
      were detected. In conclusion, the study population carries HBV preS/S variants;
      MHR and "a" determinant variant rates are high among diagnostic or immune escape
      mutants. It is important to evaluate the mutant detection performance of HBsAg
      tests.

PMID- 29642828
TI  - [Comparison of Clinical Laboratory Standards Institute (CLSI) and European
      Committee on Antimicrobial Susceptibility Testing (EUCAST) broth microdilution
      methods for determining the susceptibilities of Candida isolates].
AB  - Candida species are among the top 10 pathogens causing bloodstream infections
      associated with high morbidity, mortality. In spite of the development of new
      antifungal drugs, epidemiological studies have shown that resistance to
      antifungal drugs among Candida isolates is becoming a serious problem. The aim of
      this study was to compare the antifungal broth microdilution methods of the
      Clinical and Laboratory Standards Institute (CLSI) and European Committee on
      Antimicrobial Susceptibility Testing (EUCAST) for amphotericin B, fluconazole,
      itraconazole, voriconazole, posaconazole and anidulafungin susceptibility of
      Candida blood isolates. The study consisted of 74 Candida albicans, 67 Candida
      parapsilosis, 30 Candida glabrata, and 18 Candida tropicalis isolates. The
      minimum inhibitory concentrations were determined after 24 and 48 hour of
      incubation with CLSI method and only 24 hour of incubation with EUCAST method
      except anidulofungin. The MIC values obtained by both methods were considered to
      be compatible within +/- 2 dilution limits. The categorical agreement between
      methods for each antifungal agent was assessed using clinical break points and
      epidemiological cut-off values. The agreement (+/- 2 dilution) between the
      methods was found to be species, drug, and incubation time dependent. After 24
      hour incubation, good agreement category (> 90%) was detected between
      amphotericin B, itraconazole, posaconazole and anidulofungin, but was lower
      category (< 85%) was determined with fluconazole and voriconazole especially for
      relatively slow growing C.glabrata and C.parapsilosis isolates. Excellent
      categorical agreement (100%) was observed for amfoterisin B/C.parapsilosis,
      C.glabrata, C.tropicalis and anidulofungin/C.albicans, C.glabrata, C.tropicalis
      but least category was determined for posaconazole and C.albicans (71.6% at 24
      hour; 73% at 48 hour). In vitro resistance of therapeutically used fluconazole
      and anidulafungin determined by both methods was rare among C.albicans (1.3%,
      2.7% respectively), C.glabrata (0%, 3.3% respectively) and C.tropicalis (0%, 5.6%
      respectively) isolates but, an increase of non-susceptible isolates were observed
      among C.parapsilosis (11.9% at 24 hour of incubation; 17.9% at 48 hour of
      incubation) for fluconazole. There was also a cross resistance between
      fluconazole and voriconazole for three C.parapsilosis isolates and one multidrug
      resistant (fluconazole, itraconazole, posaconazole and anidulofungin) C.albicans
      isolate (fluconazole, itraconazole, posaconazole and anidulofungin). As a result
      in this study, it was determined thatboth methods were similar and can be used
      according to preference of laboratories. The CLSI antifungal susceptibility test
      results can be assessed at the end of 24 hour incubation, but sometimes it is
      important that the evaluation should be performed as a result of 48 hour
      incubation in slow growing species such as C.glabrata.

PMID- 29642829
TI  - [Infecting glial cells with antimony resistant Leishmania tropica: A new ex-vivo
      model].
AB  - Leishmaniasis is a vector-borne zoonotic disease that shows different clinical
      features like cutaneous, mucocutaneous, visceral and viscerotropic forms. The
      protocols used in the treatment of leishmaniasis are toxic and have many
      limitations during administration. One of the limitations of treatment is the
      resistance against the protocols in practice. There is also a need to define new
      treatment options especially for resistant patients. Ex-vivo models using primary
      cell cultures may be a good source for evaluating new drug options in patients
      with antimony resistance, in addition to in-vitro and in-vivo studies. In this
      study, it was aimed to define a new ex-vivo culture model to evaluate treatment
      options in patients with cutaneous leishmaniasis who did not respond to
      treatment. In our experimental model of ex-vivo infection, Leishmania tropica
      promastigotes isolated from a case previously diagnosed with cutaneous
      leishmaniasis were used. The primary astroglial cell culture used for the ex-vivo
      model was prepared from 2-3 days old neonatal Sprague Dawley rat brains under
      sterile conditions by the modification McCarthy's method. The astroglia cells,
      which reached sufficient density, were infected with antimony resistant L.tropica
      promastigotes. After 24 hours of incubation, the supernatant on the cells were
      collected, the cell culture plate was dried at room temperature, then fixed with
      methyl alcohol and stained with Giemsa to search for L.tropica amastigotes.
      Amastigotes were intensely observed in glia cells in primary cell cultures
      infected with L.tropica promastigotes. No promastigotes were seen on Giemsa
      stained preparations of the precipitates prepared from the bottom sediment after
      the centrifugation of the liquid medium removed from the infected plates. In this
      study, promastigotes from a cutaneous leishmaniasis patient unable to respond to
      pentavalent antimony therapy were shown to infect rat glia cells and converted to
      amastigote form. This amastigote glial cell model, as far as we know, is the
      first model in the literature produced by L.tropica. The occurrence of L.tropica
      amastigote forms in glia cells may be indicative of the ability of Leishmania
      species to infect the central nervous system. The central nervous system may be
      an area for the Leishmania amastigotes to escape from the immune system in cases
      of leishmaniasis without a treatment response. Our study is important because it
      is the first study to show the infection of glia cells with L.tropica
      amastigotes.

PMID- 29642830
TI  - [A new strategy for enhancing acanthamoebicidal activity with synthesis of
      nanoflower of Laurocerausus officinalis Roemer (cherry laurel) fruit extracts].
AB  - Pathogenic Acanthamoeba species often cause infection known as Acanthamoeba
      keratitis among people who use contact lenses. It is a type of infection that can
      result in corneal ulceration, visual loss or even blindness, if not treated.
      There are various therapeutic options available in the treatment of Acanthamoeba
      infections but they are usually tough treatments with limited efficacy. For
      instance, hydrogen peroxide (H2O2) is a commonly used contact lens disinfectant
      which is effective against Acanthamoeba but it is toxic to the cornea. For these
      reasons, new and more efficacious treatment options are required for Acanthamoeba
      infections. In this context, plants are considered natural resources for the
      discovery of new drugs. Laurocerasus officinalis Roem. (cherry laurel) (Rosaceae)
      grows in Black Sea region; and it is known as "Taflan", "Laz kirazi" or
      "Karayemis". Local people are using the seeds against diabetes, while the fruits
      are consuming as food, and used fordiuretic and passing kidney stones. It has
      also been reported that the seeds of the cherry laurel are used as an
      antiparasitic agent in this area. The aim of the study was to confirm the
      traditionally use of antiparasitic activity of this fruit and to increase the
      potential effect by means of organic-inorganic hybrid synthesis. Total phenol
      contents of methanol extracts prepared from endocarp, mesocarp and seeds of the
      fruit were calculated. The effects of methanol extracts and nano flower (NFs)
      plants synthesized from these extracts on the proliferation of Acanthamoeba
      castellanii were investigated. Thus, for the first time, novel organic-inorganic
      nanobio-antiparasitic agents called NFs were produced from cherry laurel and the
      increase in the amoebicidal activity of the NFs was elucidated. The
      characterization of NFs were determined with Scanning Electron Microscopy (SEM),
      Fourier Transform Infrared Spectrometer (FT-IR) and Energy-Dispersive X-ray (EDX)
      techniques. In addition, the catalytic activity of the fruit extracts and the NFs
      were measured against guaiacol in the presence of H2O2. The viability testing of
      A.castellanii cysts used for amoebicidal activity was performed using 4% trypan
      blue. Methanol extracts and nano-flowers were prepared at concentrations of 32,
      16, 8, 4, 2 and 1 mg/ml in 0.9% saline and distributed 200 MUl each in tubes and
      incubated in the room temperature with the addition of 200 MUl of 98% viable
      A.castellani parasites. The results were evaluated using the SPSS V.22.0 program
      and it was determined that there was a significant increase in the amoebicidal
      activity of NFs compared with the other extracts according to variance analysis
      (p<= 0.05). In the study, it was determined that samples killed parasites or
      reduced parasite proliferation at certain times. As a result, NFs synthesized
      from fruit extracts were demonstrated about three times more effective than the
      non hybrid extracts for amoebicidal activity. This situation can be explained as
      high proliferative effect of a new nano-bio-antiparasitic agent known as
      nanoflower against A.castellanii.

PMID- 29642831
TI  - [Identification of anaerobic gram-negative bacilli isolated from various clinical
      specimens and determination of antibiotic resistance profiles with E-test
      methods].
AB  - The aim of this study was to identify gram-negative anaerobic bacilli isolated
      from various clinical specimens that were obtained from patients with suspected
      anaerobic infections and to determine the antibiotic resistance profiles by using
      the antibiotic concentration gradient method. The study was performed in Afyon
      Kocatepe University Ahmet Necdet Sezer Research and Practice Hospital, Medical
      Microbiology Laboratory between 1 November 2014 and 30 October 2015. Two hundred
      and seventyeight clinical specimens accepted for anaerobic culture were enrolled
      in the study. All the samples were cultivated anaerobically by using Schaedler
      agar with 5% defibrinated sheep blood and Schaedler broth. The isolated anaerobic
      gram-negative bacilli were identified by using both the conventional methods and
      automated identification system (VITEK 2, bioMerieux, France). Antibiotic
      susceptibility tests were performed with antibiotic concentration gradient method
      (E-test, bioMerieux, France); against penicillin G, clindamycin, cefoxitin,
      metronidazole, moxifloxacin, imipenem, meropenem, ertapenem and doripenem for
      each isolate. Of the 28 isolated anaerobic gram-negative bacilli; 14 were
      identified as Bacteroides fragilis group, 9 were Prevotella spp., and 5 were
      Fusobacterium spp. The highest resistance rate was found against penicillin
      (78.5%) and resistance rates against clindamycin and cefoxitin were found as
      17.8% and 21.4%, respectively. No resistance was found against metronidazole,
      moxifloxacin, imipenem, meropenem, ertapenem and doripenem. As a result,
      isolation and identification of anaerobic bacteria are difficult, time-consuming
      and more expensive when compared with the cost of aerobic culture. The rate of
      anaerobic bacteria isolation may be increased by obtaining the appropriate
      clinical specimen and appropriate transportation of these specimens. We believe
      that the data obtained from the study in our center may offer benefits for the
      follow up and treatment of infections caused by anaerobic bacteria and may
      contribute to the current literature. Because of high resistance rate detected
      against penicillin, this antibiotic should not be used as a first choice in
      empirical treatment. Cefoxitin may be used in empirical antimicrobial treatment
      of anaerobic gram-negatives; but the rate of antibiotic resistance should be
      detected for more useful and proper treatment. The prior selection of the most
      effective antibiotic, may contribute to decrease the rate of high resistance. In
      our study, no resistance was observed against carbapenem group antibiotics and
      metronidazole; so these antibiotics should be reserved as treatment options in
      the future for infections caused by resistant gram-negative anaerobic bacteria.

PMID- 29642832
TI  - [Determination of the role of Salmonella enterica plasmids in antibiotic
      susceptibility and Caenorhabditis elegans pathogenicity].
AB  - Poultry animals and poultry associated products are important risk sources for
      Salmonellosis. S.Kentucky and S.Infantis are among the serovars frequently
      isolated from retail chickens and were reported to be isolated in Turkey. In this
      study, the role of plasmids carried by S.Kentucky and S.Infantis isolates in
      antibiotic resistance profiles of the isolates and their pathogenicity on
      Caenorhabditis elegans nematode model system were investigated. The isolates
      used, 1 of Kentucky and 2 of Infantis serotypes, were selected among food-borne
      Salmonella isolated from chicken carcass in Edirne. All three isolates were
      previously shown to contain plasmids carrying multidrug resistance and were known
      to be pathogenic on C.elegans nematode model system. S.Kentucky A10 isolate was
      resistant to ampicillin, nalidixic acid, tetracycline, ciprofloxacin,
      trimethoprim and sulphonamide and carried one plasmid with 31.6 kb size.
      S.Infantis A15 isolate was resistant to ampicillin, streptomycine, nalidixic
      acid, tetracycline, neomycin, sulphonamide and kanamycin and carried a plasmid
      with 19.9 kb size while the other S.Infantis isolate (A16) was resistant to
      streptomycin, nalidixic acid, tetracycline, trimethoprim, neomycin, sulphonamide
      and kanamycin and carried 3 plasmids with 42.4, 1.5 and 1.2 kb sizes. Plasmid
      curing experiments were performed to investigate the role of plasmids in
      antibiotic resistance and pathogenicity in C.elegans. Ethidium bromide (EtBr) dye
      was used as the plasmid curing agent. Plasmids were isolated from cultures grown
      in LB broth with different concentrations of EtBr (50, 75, 100, 125 ug/ml)
      according to the Kado-Liu method and the most effective EtBr concentration was
      determined as 125 ug/ml. C.elegans pathogenicity assays were carried out using
      plasmid cured isolates. The time 50% of the nematode die (TD50) values of the
      nematode groups fed with plasmid cured isolates were compared with previously
      obtained TD50 values of the nematode groups fed with wild type Salmonella
      isolates. Studentds t-test (p< 0.05) was used to showthe level of significance
      between TD50 values of the two groups. TD50 values of the positive control group
      fed with S.Typhimurium ATCC 14028 and the negative control group fed with
      Escherichia coli OP50 were found as 4.0 +/- 0.4 and 8.0 +/- 0.02 days,
      respectively. The differences between TD50 values of nematode groups fed with
      wild type and plasmid cured isolates were statistically significant both for
      S.Kentucky (A10) (4.9 +/- 0.04-6.2 +/- 0.1) and S.Infantis (A16) (4.4 +/- 0.01
      6.2 +/- 0.2) (p< 0.05) strains, but no significant difference was observed for
      the groups fed with wild type and plasmid cured S.Infantis (A15) (5.7 +/- 0.39
      5.8 +/- 0.16) strain. Broth microdilution method was used to determine whether
      there was any change in minimal inhibitory concentrations (MIC) of the
      antibiotics for which the isolates were resistant before plasmid elimination. No
      significant difference was found between the MIC values of the resistant
      antibiotics among Salmonella isolates carrying plasmids and with cured plasmid.
      This study is important since the first in vivo results about the role of
      Kentucky and Infantis serovar plasmids on C.elegans nematode model system were
      presented.

PMID- 29642833
TI  - [Management and treatment difficulties of multi-drug resistant pulmonary
      tuberculosis in a pediatric case].
AB  - Tuberculosis continues to be a major health problem worldwide. Multidrug
      resistant tuberculosis (MDR-TB) infection that occurs in childhood is caused by
      adult MDR-TB agents which are in circulation and resistant to primary drugs. In
      this case report a 17-month-old child with MDR-TB who was cured after a 24-month
      therapy regimen was presented. Physical examination of a 17-month-old girl
      admitted to the hospital with the cause of recurrent pneumonia revealed a rubbery
      lymphadenopathy less than 2 cm in the right upper cervical region. Crepitant
      rales were detected in the right basal on auscultation of the lung. Interferon
      gamma release assay (IGRA) and tuberculin skin (TST) tests were negative.
      Computed tomography (CT) scan of the chest showed mediastinal conglomerate
      pathologic lymphadenopathy and air bronchograms were detected near the lower lobe
      of the left lung. Treatment of isoniazid, rifampicin, pyrazinamide with the
      diagnosis of epituberculosis was started by taking a sample of gastric aspirate
      culture sample. In the sixth month of the treatment patient was admitted to our
      clinic with enlarged cervical rubbery lymphadenopathy. It was determined that
      microbiological test of gastric aspirate culture specimen was positive for
      M.tuberculosis complex resistant to isoniazid, rifampin, ethambutol,
      streptomycin, ethionamide and rifabutin. Control CT showed residual peribronchial
      infiltrations and hilar calcific lymph nodes. Hearing test, vision control and,
      thyroid function tests were performed and treatment of moxifloxacin, amikacin,
      para-amino salicylic acid, protionamide and pyrazinamide was started based on
      minor drug susceptibility results of M.tuberculosis isolate which was still
      growing in gastric aspirate culture. Gastric aspirate culture for M.tuberculosis
      was still positive after 3 months of treatment and the current treatment was
      continued. Amikacin was stopped after 6 months. Therapy regimen was stopped after
      24-months. Over the course of a follow-up period of more than 3 years, the
      clinical and radiological resultsof the patient has improved significantly. The
      clinical presentation of TB in children is often nonspecific and differs from the
      patterns seen in adults. MDR-TB cases can be seen in this age group since
      tuberculosis in children is mainly caused by transmission of drug-resistant
      strains from adults. This situation is particularly problematic due to the long
      term treatment and the lack of specific drug formulations for children.

PMID- 29642834
TI  - [Risk of travel associated tuberculosis].
AB  - Tuberculosis has spread by human movements throughout history. There have been
      reports indicating tuberculosis transmission on all travel vehicles, including
      aircrafts, ground vehicles and vessels until today. However, due to the ever
      increasing of air transportation and air travelling among countries with low and
      high tuberculosis incidence, transmission risk especially in aircrafts has become
      an important issue worldwide. But in many of the studies conducted in this
      regard, transmission of tuberculosis in aircrafts was found very low. The case of
      active tuberculosis has not yet been reported. This is due to the fact that in
      modern aircrafts, there are ventilation systems that provide hepa filtered
      laminar air flow and change the air 15-20 times per hour. The guidelines for the
      prevention of tuberculosis infection in aircrafts published by the World Health
      Organization "Tuberculosis and Air Travel, 2008" and European Centre for Disease
      Prevention and Control "RAGIDA-TB, 2014" confirm each other. According to these
      guidelines, air travelling of patients with active pulmonary tuberculosis should
      be prohibited until smears of two consecutive sputum samples become negative for
      drug susceptible cases, and cultures of two consecutive of sputum samples become
      negative for multidrug or extensively drug resistant cases. When it is reported
      that a tuberculosis patient has travelled by the aircraft, it is recommended that
      the exposed passengers should be investigated for tuberculosis infection if the
      flight duration equal to or exceeding eight hours including ground delays and the
      time elapsed between flight and diagnosis of the case is no longer than three
      months. Contact screening is only recommended for passengers sitting in the same
      row, two rows ahead and two rows behind the index case. Tuberculin skin test or
      interferon gamma release assay can be used for investigation. It is very
      difficult to determine the risk of tuberculosis transmission in ground vehicles
      like buses, subways and trains. The reason is that it is often not possible to
      access the information of the passengers travelling in these vehicles. Because
      the ventilation systems in ground vehicles are not as reliable as in aircrafts
      and the crowded environment in the ground vehicles, the risk of tuberculosis
      transmission is theoretically higher. In modelling studies, the transmission risk
      in the buses was found to be higher than the trains. In the case of regular
      travelling with an index case such as school bus riders, the risk increases
      significantly. The increased human population travelling all over the world
      nowadays has also raised concerns about travel-related tuberculosis risk.
      However, because of the limited evidence, it may be more efficient to spend time
      and resources for the other actions in order to prevent tuberculosis. In this
      review article, the transmission risk of tuberculosis in vehicles has been
      discussed.

PMID- 29642835
TI  - [Evaluation of epidemiologic and clinical features of oropharyngeal tularemia
      patients in the Eastern Anatolia Region of Turkey].
AB  - Tularemia is a zoonotic infectious disease caused by Francisella tularensis.
      Tularemia is endemic in the northern hemisphere and is usually seen in North
      America, Europe and Asia. Although the ulceroglandular tularemia is the most
      common form in these regions, the oropharyngeal form is more prevalent in Eastern
      Europe, including Turkey. The disease has importance in Turkey due to its wide
      geographic distribution and periodic outbreaks. The aim of this study was to
      determine the demographic, clinical and epidemiological characteristics of
      oropharyngeal tularemia patients. The demographic, clinical, epidemiological and
      laboratory findings of 26 tularemia patients admitted to our hospital from
      Erzurum and 5 neighbour provinces were analyzed retrospectively. Francisella
      tularensis microagglutination test (MAT) was performed for all patients whose
      clinical symptoms were consistent with tularemia and MAT titers >= 1/160 were
      considered positive. Twenty-six oropharyngeal tularemia patients (13 males and 13
      females) were included in the study. All of the patients had cervical
      lymphadenopathy (LAP) at least one month period. Twenty (76.9%) of the patients
      included in the study were living in rural areas, and 17 (65.4%) were dealing
      with livestock. It was determined that 9 (34.6%) of the patients used water from
      municipal water supply, 9 (34.6%) of the patients used water from natural water
      supply and 8 (30.8%) of the patients used both of the water supplies. The most
      common symptoms among the patients in the study were fever in 23 (88.5%)
      patients, sore throat in 24 (92.3%) patients, and cervical LAP in all of the
      patients. Thirteen (50%) of the patients were treated with streptomycin, 7
      (26.9%) with doxycycline and 6 (23.1%) with gentamicin. This is the first study
      showing that tularemia is present in Erzincan, Agri, Igdir as well as Erzurum
      provinces, and it provides that the incidence has increased in this region.
      Tularemia diagnosis is generally underestimated due to the lack of specific
      symptoms. Therefore, tularemia should also be considered in patients who have
      complaints of sore throat and cervical LAP in non-endemic regions.

PMID- 29642836
TI  - Robust volcano plot: identification of differential metabolites in the presence
      of outliers.
AB  - BACKGROUND: The identification of differential metabolites in metabolomics is
      still a big challenge and plays a prominent role in metabolomics data analyses.
      Metabolomics datasets often contain outliers because of analytical, experimental,
      and biological ambiguity, but the currently available differential metabolite
      identification techniques are sensitive to outliers. RESULTS: We propose a kernel
      weight based outlier-robust volcano plot for identifying differential metabolites
      from noisy metabolomics datasets. Two numerical experiments are used to evaluate
      the performance of the proposed technique against nine existing techniques,
      including the t-test and the Kruskal-Wallis test. Artificially generated data
      with outliers reveal that the proposed method results in a lower
      misclassification error rate and a greater area under the receiver operating
      characteristic curve compared with existing methods. An experimentally measured
      breast cancer dataset to which outliers were artificially added reveals that our
      proposed method produces only two non-overlapping differential metabolites
      whereas the other nine methods produced between seven and 57 non-overlapping
      differential metabolites. CONCLUSION: Our data analyses show that the performance
      of the proposed differential metabolite identification technique is better than
      that of existing methods. Thus, the proposed method can contribute to analysis of
      metabolomics data with outliers. The R package and user manual of the proposed
      method are available at https://github.com/nishithkumarpaul/Rvolcano .

PMID- 29642837
TI  - Approximate inference of gene regulatory network models from RNA-Seq time series
      data.
AB  - BACKGROUND: Inference of gene regulatory network structures from RNA-Seq data is
      challenging due to the nature of the data, as measurements take the form of
      counts of reads mapped to a given gene. Here we present a model for RNA-Seq time
      series data that applies a negative binomial distribution for the observations,
      and uses sparse regression with a horseshoe prior to learn a dynamic Bayesian
      network of interactions between genes. We use a variational inference scheme to
      learn approximate posterior distributions for the model parameters. RESULTS: The
      methodology is benchmarked on synthetic data designed to replicate the
      distribution of real world RNA-Seq data. We compare our method to other sparse
      regression approaches and find improved performance in learning directed
      networks. We demonstrate an application of our method to a publicly available
      human neuronal stem cell differentiation RNA-Seq time series data set to infer
      the underlying network structure. CONCLUSIONS: Our method is able to improve
      performance on synthetic data by explicitly modelling the statistical
      distribution of the data when learning networks from RNA-Seq time series.
      Applying approximate inference techniques we can learn network structures quickly
      with only moderate computing resources.

PMID- 29642838
TI  - Trends in genome-wide and region-specific genetic diversity in the Dutch-Flemish
      Holstein-Friesian breeding program from 1986 to 2015.
AB  - BACKGROUND: In recent decades, Holstein-Friesian (HF) selection schemes have
      undergone profound changes, including the introduction of optimal contribution
      selection (OCS; around 2000), a major shift in breeding goal composition (around
      2000) and the implementation of genomic selection (GS; around 2010). These
      changes are expected to have influenced genetic diversity trends. Our aim was to
      evaluate genome-wide and region-specific diversity in HF artificial insemination
      (AI) bulls in the Dutch-Flemish breeding program from 1986 to 2015. METHODS:
      Pedigree and genotype data (~ 75.5 k) of 6280 AI-bulls were used to estimate
      rates of genome-wide inbreeding and kinship and corresponding effective
      population sizes. Region-specific inbreeding trends were evaluated using regions
      of homozygosity (ROH). Changes in observed allele frequencies were compared to
      those expected under pure drift to identify putative regions under selection. We
      also investigated the direction of changes in allele frequency over time.
      RESULTS: Effective population size estimates for the 1986-2015 period ranged from
      69 to 102. Two major breakpoints were observed in genome-wide inbreeding and
      kinship trends. Around 2000, inbreeding and kinship levels temporarily dropped.
      From 2010 onwards, they steeply increased, with pedigree-based, ROH-based and
      marker-based inbreeding rates as high as 1.8, 2.1 and 2.8% per generation,
      respectively. Accumulation of inbreeding varied substantially across the genome.
      A considerable fraction of markers showed changes in allele frequency that were
      greater than expected under pure drift. Putative selected regions harboured many
      quantitative trait loci (QTL) associated to a wide range of traits. In
      consecutive 5-year periods, allele frequencies changed more often in the same
      direction than in opposite directions, except when comparing the 1996-2000 and
      2001-2005 periods. CONCLUSIONS: Genome-wide and region-specific diversity trends
      reflect major changes in the Dutch-Flemish HF breeding program. Introduction of
      OCS and the shift in breeding goal were followed by a drop in inbreeding and
      kinship and a shift in the direction of changes in allele frequency. After
      introduction of GS, rates of inbreeding and kinship increased substantially while
      allele frequencies continued to change in the same direction as before GS. These
      results provide insight in the effect of breeding practices on genomic diversity
      and emphasize the need for efficient management of genetic diversity in GS
      schemes.

PMID- 29642839
TI  - TIA: algorithms for development of identity-linked SNP islands for analysis by
      massively parallel DNA sequencing.
AB  - BACKGROUND: Single nucleotide polymorphisms (SNPs) located within the human
      genome have been shown to have utility as markers of identity in the
      differentiation of DNA from individual contributors. Massively parallel DNA
      sequencing (MPS) technologies and human genome SNP databases allow for the design
      of suites of identity-linked target regions, amenable to sequencing in a
      multiplexed and massively parallel manner. Therefore, tools are needed for
      leveraging the genotypic information found within SNP databases for the discovery
      of genomic targets that can be evaluated on MPS platforms. RESULTS: The SNP
      island target identification algorithm (TIA) was developed as a user-tunable
      system to leverage SNP information within databases. Using data within the 1000
      Genomes Project SNP database, human genome regions were identified that contain
      globally ubiquitous identity-linked SNPs and that were responsive to targeted
      resequencing on MPS platforms. Algorithmic filters were used to exclude target
      regions that did not conform to user-tunable SNP island target characteristics.
      To validate the accuracy of TIA for discovering these identity-linked SNP islands
      within the human genome, SNP island target regions were amplified from 70
      contributor genomic DNA samples using the polymerase chain reaction. Multiplexed
      amplicons were sequenced using the Illumina MiSeq platform, and the resulting
      sequences were analyzed for SNP variations. 166 putative identity-linked SNPs
      were targeted in the identified genomic regions. Of the 309 SNPs that provided
      discerning power across individual SNP profiles, 74 previously undefined SNPs
      were identified during evaluation of targets from individual genomes. Overall,
      DNA samples of 70 individuals were uniquely identified using a subset of the
      suite of identity-linked SNP islands. CONCLUSIONS: TIA offers a tunable genome
      search tool for the discovery of targeted genomic regions that are scalable in
      the population frequency and numbers of SNPs contained within the SNP island
      regions. It also allows the definition of sequence length and sequence
      variability of the target region as well as the less variable flanking regions
      for tailoring to MPS platforms. As shown in this study, TIA can be used to
      discover identity-linked SNP islands within the human genome, useful for
      differentiating individuals by targeted resequencing on MPS technologies.

PMID- 29642840
TI  - iSeg: an efficient algorithm for segmentation of genomic and epigenomic data.
AB  - BACKGROUND: Identification of functional elements of a genome often requires
      dividing a sequence of measurements along a genome into segments where adjacent
      segments have different properties, such as different mean values. Despite dozens
      of algorithms developed to address this problem in genomics research, methods
      with improved accuracy and speed are still needed to effectively tackle both
      existing and emerging genomic and epigenomic segmentation problems. RESULTS: We
      designed an efficient algorithm, called iSeg, for segmentation of genomic and
      epigenomic profiles. iSeg first utilizes dynamic programming to identify
      candidate segments and test for significance. It then uses a novel data structure
      based on two coupled balanced binary trees to detect overlapping significant
      segments and update them simultaneously during searching and refinement stages.
      Refinement and merging of significant segments are performed at the end to
      generate the final set of segments. By using an objective function based on the p
      values of the segments, the algorithm can serve as a general computational
      framework to be combined with different assumptions on the distributions of the
      data. As a general segmentation method, it can segment different types of genomic
      and epigenomic data, such as DNA copy number variation, nucleosome occupancy,
      nuclease sensitivity, and differential nuclease sensitivity data. Using simple t
      tests to compute p-values across multiple datasets of different types, we
      evaluate iSeg using both simulated and experimental datasets and show that it
      performs satisfactorily when compared with some other popular methods, which
      often employ more sophisticated statistical models. Implemented in C++, iSeg is
      also very computationally efficient, well suited for large numbers of input
      profiles and data with very long sequences. CONCLUSIONS: We have developed an
      efficient general-purpose segmentation tool and showed that it had comparable or
      more accurate results than many of the most popular segment-calling algorithms
      used in contemporary genomic data analysis. iSeg is capable of analyzing datasets
      that have both positive and negative values. Tunable parameters allow users to
      readily adjust the statistical stringency to best match the biological nature of
      individual datasets, including widely or sparsely mapped genomic datasets or
      those with non-normal distributions.

PMID- 29642842
TI  - GROOLS: reactive graph reasoning for genome annotation through biological
      processes.
AB  - BACKGROUND: High quality functional annotation is essential for understanding the
      phenotypic consequences encoded in a genome. Despite improvements in
      bioinformatics methods, millions of sequences in databanks are not assigned
      reliable functions. The curation of protein functions in the context of
      biological processes is a way to evaluate and improve their annotation. RESULTS:
      We developed an expert system using paraconsistent logic, named GROOLS (Genomic
      Rule Object-Oriented Logic System), that evaluates the completeness and the
      consistency of predicted functions through biological processes like metabolic
      pathways. Using a generic and hierarchical representation of knowledge,
      biological processes are modeled in a graph from which observations (i.e.
      predictions and expectations) are propagated by rules. At the end of the
      reasoning, conclusions are assigned to biological process components and
      highlight uncertainties and inconsistencies. Results on 14 microbial organisms
      are presented. CONCLUSIONS: GROOLS software is designed to evaluate the overall
      accuracy of functional unit and pathway predictions according to organism
      experimental data like growth phenotypes. It assists biocurators in the
      functional annotation of proteins by focusing on missing or contradictory
      observations.

PMID- 29642841
TI  - Encompassing new use cases - level 3.0 of the HUPO-PSI format for molecular
      interactions.
AB  - BACKGROUND: Systems biologists study interaction data to understand the behaviour
      of whole cell systems, and their environment, at a molecular level. In order to
      effectively achieve this goal, it is critical that researchers have high quality
      interaction datasets available to them, in a standard data format, and also a
      suite of tools with which to analyse such data and form experimentally testable
      hypotheses from them. The PSI-MI XML standard interchange format was initially
      published in 2004, and expanded in 2007 to enable the download and interchange of
      molecular interaction data. PSI-XML2.5 was designed to describe experimental data
      and to date has fulfilled this basic requirement. However, new use cases have
      arisen that the format cannot properly accommodate. These include data abstracted
      from more than one publication such as allosteric/cooperative interactions and
      protein complexes, dynamic interactions and the need to link kinetic and affinity
      data to specific mutational changes. RESULTS: The Molecular Interaction workgroup
      of the HUPO-PSI has extended the existing, well-used XML interchange format for
      molecular interaction data to meet new use cases and enable the capture of new
      data types, following extensive community consultation. PSI-MI XML3.0 expands the
      capabilities of the format beyond simple experimental data, with a concomitant
      update of the tool suite which serves this format. The format has been
      implemented by key data producers such as the International Molecular Exchange
      (IMEx) Consortium of protein interaction databases and the Complex Portal.
      CONCLUSIONS: PSI-MI XML3.0 has been developed by the data producers, data users,
      tool developers and database providers who constitute the PSI-MI workgroup. This
      group now actively supports PSI-MI XML2.5 as the main interchange format for
      experimental data, PSI-MI XML3.0 which additionally handles more complex data
      types, and the simpler, tab-delimited MITAB2.5, 2.6 and 2.7 for rapid parsing and
      download.

PMID- 29642843
TI  - IntEREst: intron-exon retention estimator.
AB  - BACKGROUND: In-depth study of the intron retention levels of transcripts provide
      insights on the mechanisms regulating pre-mRNA splicing efficiency. Additionally,
      detailed analysis of retained introns can link these introns to post
      transcriptional regulation or identify aberrant splicing events in human
      diseases. RESULTS: We present IntEREst, Intron-Exon Retention Estimator, an R
      package that supports rigorous analysis of non-annotated intron retention events
      (in addition to the ones annotated by RefSeq or similar databases), and support
      intra-sample in addition to inter-sample comparisons. It accepts binary sequence
      alignment/map (.bam) files as input and determines genome-wide estimates of
      intron retention or exon-exon junction levels. Moreover, it includes functions
      for comparing subsets of user-defined introns (e.g. U12-type vs U2-type) and its
      plotting functions allow visualization of the distribution of the retention
      levels of the introns. Statistical methods are adapted from the DESeq2, edgeR and
      DEXSeq R packages to extract the significantly more or less retained introns.
      Analyses can be performed either sequentially (on single core) or in parallel (on
      multiple cores). We used IntEREst to investigate the U12- and U2-type intron
      retention in human and plant RNAseq dataset with defects in the U12-dependent
      spliceosome due to mutations in the ZRSR2 component of this spliceosome.
      Additionally, we compared the retained introns discovered by IntEREst with that
      of other methods and studies. CONCLUSION: IntEREst is an R package for Intron
      retention and exon-exon junction levels analysis of RNA-seq data. Both the human
      and plant analyses show that the U12-type introns are retained at higher level
      compared to the U2-type introns already in the control samples, but the retention
      is exacerbated in patient or plant samples carrying a mutated ZRSR2 gene. Intron
      retention events caused by ZRSR2 mutation that we discovered using IntEREst
      (DESeq2 based function) show considerable overlap with the retained introns
      discovered by other methods (e.g. IRFinder and edgeR based function of IntEREst).
      Our results indicate that increase in both the number of biological replicates
      and the depth of sequencing library promote the discovery of retained introns,
      but the effect of library size gradually decreases with more than 35 million
      reads mapped to the introns.

PMID- 29642844
TI  - Contrasting life histories contribute to divergent patterns of genetic diversity
      and population connectivity in freshwater sculpin fishes.
AB  - BACKGROUND: Life history characteristics are considered important factors
      influencing the evolutionary processes of natural populations, including the
      patterns of population genetic structure of a species. The sister species Cottus
      hangiongensis and C. koreanus are small bottom-dwelling freshwater sculpin fishes
      from South Korea that display marked life history divergence but are
      morphologically nearly indistinguishable. Cottus hangiongensis evolved an
      'amphidromous' life history with a post-hatching pelagic larval phase. They spawn
      many small eggs in the low reaches of rivers, and hatched larvae migrate to the
      sea before returning to grow to maturity in the river mouth. In contrast, C.
      koreanus evolved a 'fluvial' landlocked type with benthic larvae. They release a
      smaller number of larger eggs, and the larvae undergo direct development,
      remaining benthic in the upstream rivers throughout their entire lives. We tested
      whether there were differences in patterns and levels of within-population
      genetic diversities and spatial population structure between the two closely
      related Korean sculpins using mitochondrial DNA control region sequences and
      seven nuclear microsatellite loci. RESULTS: The combined analyses of both marker
      sets revealed that C. hangiongensis harboured considerably higher levels of
      within-population genetic diversities (e.g. haplotype/allelic richness,
      heterozygosities) than C. koreanus. In contrast, the fluvial sculpin exhibited
      noticeably more spatial population structure than did the amphidromous sculpin,
      as suggested by pairwise FST statistics. The finding that C. hangiongensis
      individuals comprised a single random mating population across the east-flowing
      river basins in the Korean Peninsula, whereas C. koreanus individuals comprised
      genetically discrete individual populations, was further supported by an
      individual-based Bayesian population assignment and also factorial correspondence
      analyses. CONCLUSIONS: The higher genetic diversity, but lower population
      structure, of the amphidromous sculpin relative to the fluvial sculpin may have
      resulted from its greater larval dispersal and also possibly, higher fecundity
      accompanied by an amphidromous life history. Hence, we conclude that contrasting
      early life histories - including the presence or absence of the pelagic larval
      phase - may have led to divergent patterns of within-population genetic
      diversities and spatial population structure between the sister Cottus species
      following speciation from a common ancestor of marine sculpin.

PMID- 29642845
TI  - Prognostic value of liver stiffness in HIV/HCV-Coinfected patients with
      decompensated cirrhosis.
AB  - BACKGROUND: Little is known about the utility of transient elastography (TE) for
      assessing the prognosis of patients with decompensated cirrhosis (DC). METHODS:
      We analyzed HIV/HCV-coinfected patients with DC who underwent TE as part of their
      routine follow-up between 2006 and 2015. We also calculated the liver stiffness
      spleen diameter-to-platelet score (LSPS), FIB-4 index, albumin, MELD score, and
      Child-Pugh score. The primary outcome was death. RESULTS: The study population
      comprised 65 patients. After a median follow-up of 32 months after the first TE,
      17 patients had received anti-HCV therapy and 31 patients had died. The highest
      area under the receiver operating characteristic curve (AUROC) value for
      prediction of death was observed with albumin (0.695), followed by Child-Pugh
      score (0.648), both with P values < .05. Lower AUROC values were observed with
      MELD score (0.633), TE (0.618), LSPS score (0.595), and FIB-4 (0.569), all with P
      values > .05. In the univariate Cox regression analysis, albumin, FIB-4, Child
      Pugh score, and MELD score, but not TE, were associated with death. In the
      multivariate analysis, albumin and Child-Pugh score were the only baseline
      variables associated with death. CONCLUSIONS: Our results suggest that TE is not
      useful for assessing the prognosis of HIV-infected patients with decompensated
      HCV-related cirrhosis. Albumin concentration and Child-Pugh scores were the most
      consistent predictors of death in this population group.

PMID- 29642846
TI  - JAMI: a Java library for molecular interactions and data interoperability.
AB  - BACKGROUND: A number of different molecular interactions data download formats
      now exist, designed to allow access to these valuable data by diverse user
      groups. These formats include the PSI-XML and MITAB standard interchange formats
      developed by Molecular Interaction workgroup of the HUPO-PSI in addition to
      other, use-specific downloads produced by other resources. The onus is currently
      on the user to ensure that a piece of software is capable of read/writing all
      necessary versions of each format. This problem may increase, as data providers
      strive to meet ever more sophisticated user demands and data types. RESULTS: A
      collaboration between EMBL-EBI and the University of Cambridge has produced JAMI,
      a single library to unify standard molecular interaction data formats such as PSI
      MI XML and PSI-MITAB. The JAMI free, open-source library enables the development
      of molecular interaction computational tools and pipelines without the need to
      produce different versions of software to read different versions of the data
      formats. CONCLUSION: Software and tools developed on top of the JAMI framework
      are able to integrate and support both PSI-MI XML and PSI-MITAB. The use of JAMI
      avoids the requirement to chain conversions between formats in order to reach a
      desired output format and prevents code and unit test duplication as the code
      becomes more modular. JAMI's model interfaces are abstracted from the underlying
      format, hiding the complexity and requirements of each data format from
      developers using JAMI as a library.

PMID- 29642847
TI  - The relationship and mechanism between education and functional health status
      transition among older persons in China.
AB  - BACKGROUND: Despite decades of study, debates exist surrounding the relationship
      between education and functional health status transition among elderly
      populations. This study aims to add evidence to the debates using China as a case
      study. Specifically, this study analysed the association of education with
      functional health status transition and then the mechanism behind that
      association using the budget constraint relax hypothesis and the efficiency
      improvement hypothesis among elderly population in China. METHODS: Based on data
      from the Chinese Longitudinal Healthy Longevity Surveys from 2008 and 2011, this
      study focussed on adults aged 65 years and above, with a final sample size of
      12,112. A generalised structural equation model was used to analyse the
      relationship between education and functional health status transition and the
      mechanism behind that association. RESULTS: During the three examined years,
      among elderly adults who were nondisabled at baseline, 53.1% stayed nondisabled,
      14.6% became disabled, and 32.3% died; among those disabled in 2008, 8.1%
      recovered, 21.6% stayed disabled, and 70.3% died. Compared with older adults
      without any education, those who had attended primary schools had both lower
      mortality and disability, whereas those who had attended high schools and above
      only had a lower mortality rate. The budget constraint relax hypothesis and the
      efficiency improvement hypothesis explained the majority of the relationship
      between education and transition from non-disability to death, but hardly
      explained the transition from non-disability to disability. Furthermore, once a
      person was disabled, education had no significant relationship with functional
      ability recovery or mortality. CONCLUSIONS: Attending primary school seems to
      provide the highest benefit to functional health status transition among older
      and nondisabled persons in China. Those who attended high schools and above are
      expected to live a longer life with disability. The mechanism between education
      and the onset of disability needs more discussion.

PMID- 29642848
TI  - A two-tiered unsupervised clustering approach for drug repositioning through
      heterogeneous data integration.
AB  - BACKGROUND: Drug repositioning is the process of identifying new uses for
      existing drugs. Computational drug repositioning methods can reduce the time,
      costs and risks of drug development by automating the analysis of the
      relationships in pharmacology networks. Pharmacology networks are large and
      heterogeneous. Clustering drugs into small groups can simplify large pharmacology
      networks, these subgroups can also be used as a starting point for repositioning
      drugs. In this paper, we propose a two-tiered drug-centric unsupervised
      clustering approach for drug repositioning, integrating heterogeneous drug data
      profiles: drug-chemical, drug-disease, drug-gene, drug-protein and drug-side
      effect relationships. RESULTS: The proposed drug repositioning approach is
      threefold; (i) clustering drugs based on their homogeneous profiles using the
      Growing Self Organizing Map (GSOM); (ii) clustering drugs based on drug-drug
      relation matrices based on the previous step, considering three state-of-the-art
      graph clustering methods; and (iii) inferring drug repositioning candidates and
      assigning a confidence value for each identified candidate. In this paper, we
      compare our two-tiered clustering approach against two existing heterogeneous
      data integration approaches with reference to the Anatomical Therapeutic Chemical
      (ATC) classification, using GSOM. Our approach yields Normalized Mutual
      Information (NMI) and Standardized Mutual Information (SMI) of 0.66 and 36.11,
      respectively, while the two existing methods yield NMI of 0.60 and 0.64 and SMI
      of 22.26 and 33.59. Moreover, the two existing approaches failed to produce
      useful cluster separations when using graph clustering algorithms while our
      approach is able to identify useful clusters for drug repositioning. Furthermore,
      we provide clinical evidence for four predicted results (Chlorthalidone,
      Indomethacin, Metformin and Thioridazine) to support that our proposed approach
      can be reliably used to infer ATC code and drug repositioning. CONCLUSION: The
      proposed two-tiered unsupervised clustering approach is suitable for drug
      clustering and enables heterogeneous data integration. It also enables
      identifying reliable repositioning drug candidates with reference to ATC
      therapeutic classification. The repositioning drug candidates identified
      consistently by multiple clustering algorithms and with high confidence have a
      higher possibility of being effective repositioning candidates.

PMID- 29642849
TI  - Impact of brain arousal and time-on-task on autonomic nervous system activity in
      the wake-sleep transition.
AB  - BACKGROUND: Autonomic nervous system (ANS) activity has been shown to vary with
      the state of brain arousal. In a previous study, this association of ANS activity
      with distinct states of brain arousal was demonstrated using 15-min EEG data, but
      without directly controlling for possible time-on-task effects. In the current
      study we examine ANS-activity in fine-graded EEG-vigilance stages (indicating
      states of brain arousal) during two conditions of a 2-h oddball task while
      controlling for time-on-task. In addition, we analyze the effect of time-on-task
      on ANS-activity while holding the level of brain arousal constant. METHODS: Heart
      rate and skin conductance level of healthy participants were recorded during a 2
      h EEG with eyes closed under simultaneous presentation of stimuli in an ignored
      (N = 39) and attended (N = 39) oddball condition. EEG-vigilance stages were
      classified using the Vigilance Algorithm Leipzig (VIGALL 2.1). The time-on-task
      effect was tested by dividing the EEG into four 30-min consecutive time blocks.
      ANS-activity was compared between EEG-vigilance stages across the entire 2 h and
      within each time block. RESULTS: We found a coherent decline of ANS-activity with
      declining brain arousal states, over the 2-h recording and in most cases within
      each 30-min block in both conditions. Furthermore, we found a significant time-on
      task effect on heart rate, even when arousal was kept constant. It was most
      pronounced between the first and all subsequent blocks and could have been a
      consequence of postural change at the beginning of the experiment. CONCLUSION:
      Our findings contribute to the validation of VIGALL 2.1 using ANS parameters in 2
      h EEG recording under oddball conditions.

PMID- 29642850
TI  - Using observational facial descriptors to infer pain in persons with and without
      dementia.
AB  - BACKGROUND: For patients with advanced dementia, pain diagnosis and assessment
      requires observations of pain-indicative behavior by others. One type of behavior
      that has been shown to be a promising candidate is the facial response to pain.
      To further test how pain-indicative facial responses are, we investigated the
      predictive power of observational facial descriptors to (i) predict the self
      report of pain and (ii) to differentiate between non-painful and painful
      conditions. In addition, the expertise of the observers (nurses vs. healthy
      controls) and the cognitive status of the observed (dementia vs. cognitively
      healthy) were considered. METHODS: Overall 62 participants (32 nurses and 30
      control subjects) watched 40 video-clips, showing facial expressions of older
      individuals with and without dementia during non-painful and painful pressure
      stimulation. After each clip, participants were asked to rate the videos using
      commonly used facial descriptors of pain and also to provide global pain estimate
      ratings of how much pain the observed individual might have experienced. RESULTS:
      Out of the 12 facial descriptors used, only 7 were able to differentiate between
      non-painful and painful conditions. Moreover, participants were better in
      predicting the pain self-report of the observed individuals when using facial
      descriptors than when using global pain estimates. Especially, the anatomically
      orienting descriptors (e.g. opened mouth, narrowing eyes) showed greatest
      predictive power. Results were not affected by pain-expertise of the observers
      (nurses vs. control subjects) or diagnostic status of the observed (patients with
      dementia vs. cognitively unimpaired subjects). CONCLUSIONS: The fine-grained and
      specific observation of facial responses to acute pain appeared to provide valid
      indication of pain that is not compromised when patients with dementia are
      observed. The regular professional training does not put nurses at advantage to
      detect pain via facial responses.

PMID- 29642852
TI  - Parapatric genetic divergence among deep evolutionary lineages in the
      Mediterranean green crab, Carcinus aestuarii (Brachyura, Portunoidea,
      Carcinidae), accounts for a sharp phylogeographic break in the Eastern
      Mediterranean.
AB  - BACKGROUND: Recently, population genetic studies of Mediterranean marine species
      highlighted patterns of genetic divergence and phylogeographic breaks, due to the
      interplay between impacts of Pleistocene climate shifts and contemporary
      hydrographical barriers. These factors markedly shaped the distribution of marine
      organisms and their genetic makeup. The present study is part of an ongoing
      effort to understand the phylogeography and evolutionary history of the highly
      dispersive Mediterranean green crab, Carcinus aestuarii (Nardo, 1847), across the
      Mediterranean Sea. Recently, marked divergence between two highly separated
      haplogroups (genetic types I and II) of C. aestuarii was discerned across the
      Siculo-Tunisian Strait, suggesting an Early Pleistocene vicariant event. In order
      to better identify phylogeographic patterns in this species, a total of 263
      individuals from 22 Mediterranean locations were analysed by comparing a 587
      basepair region of the mitochondrial gene Cox1 (cytochrome oxidase subunit 1).
      The examined dataset is composed of both newly generated sequences (76) and
      previously investigated ones (187). RESULTS: Our results unveiled the occurrence
      of a highly divergent haplogroup (genetic type III) in the most north-eastern
      part of the Mediterranean Sea. Divergence between the most distinct type III and
      the common ancestor of both types I and II corresponds to the Early Pleistocene
      and coincides with the historical episode of separation between types I and II.
      Our results also revealed strong genetic divergence among adjacent regions
      (separating the Aegean and Marmara seas from the remaining distribution zone) and
      confirmed a sharp phylogeographic break across the Eastern Mediterranean. The
      recorded parapatric genetic divergence, with the potential existence of a contact
      zone between both groups in the Ionian Sea and notable differences in the
      demographic history, suggest the likely impact of paleoclimatic events, as well
      as past and contemporary oceanographic processes, in shaping genetic variability
      of this species. CONCLUSIONS: Our findings not only provide further evidence for
      the complex evolutionary history of the green crab in the Mediterranean Sea, but
      also stress the importance of investigating peripheral areas in the species'
      distribution zone in order to fully understand the distribution of genetic
      diversity and unravel hidden genetic units and local patterns of endemism.

PMID- 29642851
TI  - Tracing the evolution of the heterotrimeric G protein alpha subunit in Metazoa.
AB  - BACKGROUND: Heterotrimeric G proteins are fundamental signaling proteins composed
      of three subunits, Galpha and a Gbetagamma dimer. The role of Galpha as a
      molecular switch is critical for transmitting and amplifying intracellular
      signaling cascades initiated by an activated G protein Coupled Receptor (GPCR).
      Despite their biochemical and therapeutic importance, the study of G protein
      evolution has been limited to the scope of a few model organisms. Furthermore, of
      the five primary Galpha subfamilies, the underlying gene structure of only two
      families has been thoroughly investigated outside of Mammalia evolution.
      Therefore our understanding of Galpha emergence and evolution across phylogeny
      remains incomplete. RESULTS: We have computationally identified the presence and
      absence of every Galpha gene (GNA-) across all major branches of Deuterostomia
      and evaluated the conservation of the underlying exon-intron structures across
      these phylogenetic groups. We provide evidence of mutually exclusive exon
      inclusion through alternative splicing in specific lineages. Variations of splice
      site conservation and isoforms were found for several paralogs which coincide
      with conserved, putative motifs of DNA-/RNA-binding proteins. In addition to our
      curated gene annotations, within Primates, we identified 15 retrotranspositions,
      many of which have undergone pseudogenization. Most importantly, we find numerous
      deviations from previous findings regarding the presence and absence of
      individual GNA- genes, nuanced differences in phyla-specific gene copy numbers,
      novel paralog duplications and subsequent intron gain and loss events.
      CONCLUSIONS: Our curated annotations allow us to draw more accurate inferences
      regarding the emergence of all Galpha family members across Metazoa and to
      present a new, updated theory of Galpha evolution. Leveraging this, our results
      are critical for gaining new insights into the co-evolution of the Galpha subunit
      and its many protein binding partners, especially therapeutically relevant G
      protein - GPCR signaling pathways which radiated in Vertebrata evolution.

PMID- 29642853
TI  - A comparative genomics study of carbohydrate/glucose metabolic genes: from fish
      to mammals.
AB  - BACKGROUND: Glucose plays a key role as an energy source in most mammals, but its
      importance in fish appears to be limited that so far seemed to belong to diabetic
      humans only. Several laboratories worldwide have made important efforts in order
      to better understand this strange phenotype observed in fish. However, the
      mechanism of carbohydrate/glucose metabolism is astonishingly complex. Why basal
      glycaemia is different between fish and mammals and how carbohydrate metabolism
      is different amongst organisms is largely uncharted territory. The utilization of
      comparative systems biology with model vertebrates to explore fish metabolism has
      become an essential approach to unravelling hidden in vivo mechanisms. RESULTS:
      In this study, we first built a database containing 791, 593, 523, 666 and 698
      carbohydrate/glucose metabolic genes from the genomes of Danio rerio, Xenopus
      tropicalis, Gallus gallus, Mus musculus and Homo sapiens, respectively, and most
      of these genes in our database are predicted to encode specific enzymes that play
      roles in defined reactions; over 57% of these genes are related to human type 2
      diabetes. Then, we systematically compared these genes and found that more than
      70% of the carbohydrate/glucose metabolic genes are conserved in the five
      species. Interestingly, there are 4 zebrafish-specific genes (si:ch211-167b20.8,
      CABZ01043017.1, socs9 and eif4e1c) and 1 human-specific gene (CALML6) that may
      alter glucose utilization in their corresponding species. Interestingly, these 5
      genes are all carbohydrate regulation factors, but the enzymes themselves are
      involved in insulin regulation pathways. Lastly, in order to facilitate the use
      of our data sets, we constructed a glucose metabolism database platform (
      http://101.200.43.1:10000/ ). CONCLUSIONS: This study provides the first
      systematic genomic insights into carbohydrate/glucose metabolism. After
      exhaustive analysis, we found that most metabolic genes are conserved in
      vertebrates. This work may resolve some of the complexities of
      carbohydrate/glucose metabolic heterogeneity amongst different vertebrates and
      may provide a reference for the treatment of diabetes and for applications in the
      aquaculture industry.

PMID- 29642855
TI  - MiR-30a-5p confers cisplatin resistance by regulating IGF1R expression in
      melanoma cells.
AB  - BACKGROUND: Melanoma is notoriously resistant to all current modalities of cancer
      therapies including chemotherapy. In recent years, microRNAs (miRNAs) have
      emerged as molecular regulators in the development and progression of melanoma.
      However, the relationship between microRNA and chemo-resistance of melanoma is
      little known. In present study, we aimed to investigate the miRNAs related to
      cisplatin-resistance in melanoma cells. METHODS: After cisplatin (DDP) resistant
      melanoma cells (M8/DDP and SK-Mel-19/DDP) were established in-vitro, high
      throughput screening of differentially expressed miRNAs between resistant cells
      and parental cells were performed. RESULTS: It was found that a cancer-related
      miRNA, miR-30a-5p, was highly over-expressed in resistant cells. Transfection of
      miR-30a-5p mimic or inhibitor could alter the sensitivity of melanoma cells to
      cisplatin. Next, we showed that Insulin Like Growth Factor 1 Receptor (IGF1R)
      gene turned out to be a direct target of miR-30a-5p. Knockdown of IGF1R in
      melanoma cells could not only reduce the sensitivity to cisplatin but also lead
      to cell cycle arrest by regulating phosphorylation of Serine-Threonine Protein
      Kinase (P-AKT (Ser473)) and Tumor Protein P53 (P53). CONCLUSION: Taken together,
      our study demonstrated that miR-30a-5p could influence chemo-resistance by
      targeting IGF1R gene in melanoma cells, which might provide a potential target
      for the therapy of chemo-resistant melanoma cells.

PMID- 29642854
TI  - Comparative transcriptome analysis of hypothalamus-regulated feed intake induced
      by exogenous visfatin in chicks.
AB  - BACKGROUND: The intracerebroventricular injection of visfatin increases feed
      intake. However, little is known about the molecular mechanism in chicks. This
      study was conducted to assess the effect of visfatin on the feeding behavior of
      chicks and the associated molecular mechanism. RESULTS: In response to the
      intraventricular injection of 40 ng and 400 ng visfatin, feed intake in chicks
      was significantly increased, and the concentrations of glucose, insulin, TG, HDL
      and LDL were significantly altered. Using RNA-seq, we identified DEGs in the
      chick hypothalamus at 60 min after injection with various doses of visfatin. In
      total, 325, 85 and 519 DEGs were identified in the treated chick hypothalamus in
      the LT vs C, HT vs C and LT vs HT comparisons, respectively. The changes in the
      expression profiles of DEGs, GO functional categories, KEGG pathways, and PPI
      networks by visfatin-mediated regulation of feed intake were analyzed. The DEGs
      were grouped into 8 clusters based on their expression patterns via K-mean
      clustering; there were 14 appetite-related DEGs enriched in the hormone activity
      GO term. The neuroactive ligand-receptor interaction pathway was the key pathway
      affected by visfatin. The PPI analysis of DEGs showed that POMC was a hub gene
      that interacted with the maximum number of nodes and ingestion-related pathways,
      including POMC, CRH, AgRP, NPY, TRH, VIP, NPYL, CGA and TSHB. CONCLUSION: These
      common DEGs were enriched in the hormone activity GO term and the neuroactive
      ligand-receptor interaction pathway. Therefore, visfatin causes hyperphagia via
      the POMC/CRH and NPY/AgRP signaling pathways. These results provide valuable
      information about the molecular mechanisms of the regulation of food intake by
      visfatin.

PMID- 29642856
TI  - Operational utility of the reverse-transcription recombinase polymerase
      amplification for detection of dengue virus.
AB  - BACKGROUND: A method for rapid detection of dengue virus using the reverse
      transcription recombinase polymerase amplification (RT-RPA) was recently
      developed, evaluated and made ready for deployment. However, reliance solely on
      the evaluation performed by experienced researchers in a well-structured and well
      equipped reference laboratory may overlook the potential intrinsic problems that
      may arise during deployment of the assay into new application sites, especially
      for users unfamiliar with the test. Appropriate assessment of this newly
      developed assay by users who are unfamiliar with the assay is, therefore, vital.
      METHODS: An operational utility test to elucidate the efficiency and
      effectiveness of the dengue RT-RPA assay was conducted among a group of
      researchers new to the assay. Nineteen volunteer researchers with different
      research experience were recruited. The participants performed the RT-RPA assay
      and interpreted the test results according to the protocol provided. Deviation
      from the protocol was identified and tabulated by trained facilitators. Post-test
      questionnaires were conducted to determine the user satisfaction and
      acceptability of the dengue RT-RPA assay. RESULTS: All the participants completed
      the test and successfully interpreted the results according to the provided
      instructions, regardless of their research experience. Of the 19 participants,
      three (15.8%) performed the assay with no deviations and 16 (84.2%) performed the
      assay with only 1 to 5 deviations. The number of deviations from protocol,
      however, was not correlated with the user laboratory experience. The accuracy of
      the results was also not affected by user laboratory experience. The concordance
      of the assay results against that of the expected was at 89.3%. The user
      satisfaction towards the RT-RPA protocol and interpretation of results was 90%
      and 100%, respectively. CONCLUSIONS: The dengue RT-RPA assay can be successfully
      performed by simply following the provided written instructions. Deviations from
      the written protocols did not adversely affect the outcome of the assay. These
      suggest that the RT-RPA assay is indeed a simple, robust and efficient laboratory
      method for detection of dengue virus. Furthermore, high new user acceptance of
      the RT-RPA assay suggests that this assay could be successfully deployed into new
      laboratories where RT-RPA was not previously performed.

PMID- 29642857
TI  - Structure and transcriptional regulation of the major intrinsic protein gene
      family in grapevine.
AB  - BACKGROUND: The major intrinsic protein (MIP) family is a family of proteins,
      including aquaporins, which facilitate water and small molecule transport across
      plasma membranes. In plants, MIPs function in a huge variety of processes
      including water transport, growth, stress response, and fruit development. In
      this study, we characterize the structure and transcriptional regulation of the
      MIP family in grapevine, describing the putative genome duplication events
      leading to the family structure and characterizing the family's tissue and
      developmental specific expression patterns across numerous preexisting microarray
      and RNAseq datasets. Gene co-expression network (GCN) analyses were carried out
      across these datasets and the promoters of each family member were analyzed for
      cis-regulatory element structure in order to provide insight into their
      transcriptional regulation. RESULTS: A total of 29 Vitis vinifera MIP family
      members (excluding putative pseudogenes) were identified of which all but two
      were mapped onto Vitis vinifera chromosomes. In this study, segmental duplication
      events were identified for five plasma membrane intrinsic protein (PIP) and four
      tonoplast intrinsic protein (TIP) genes, contributing to the expansion of PIPs
      and TIPs in grapevine. Grapevine MIP family members have distinct tissue and
      developmental expression patterns and hierarchical clustering revealed two
      primary groups regardless of the datasets analyzed. Composite microarray and RNA
      seq gene co-expression networks (GCNs) highlighted the relationships between MIP
      genes and functional categories involved in cell wall modification and transport,
      as well as with other MIPs revealing a strong co-regulation within the family
      itself. Some duplicated MIP family members have undergone sub-functionalization
      and exhibit distinct expression patterns and GCNs. Cis-regulatory element (CRE)
      analyses of the MIP promoters and their associated GCN members revealed
      enrichment for numerous CREs including AP2/ERFs and NACs. CONCLUSIONS: Combining
      phylogenetic analyses, gene expression profiling, gene co-expression network
      analyses, and cis-regulatory element enrichment, this study provides a
      comprehensive overview of the structure and transcriptional regulation of the
      grapevine MIP family. The study highlights the duplication and sub
      functionalization of the family, its strong coordinated expression with genes
      involved in growth and transport, and the putative classes of TFs responsible for
      its regulation.

PMID- 29642858
TI  - Vaginal birth after caesarean versus elective repeat caesarean delivery after one
      previous caesarean section: a cost-effectiveness analysis in four European
      countries.
AB  - BACKGROUND: The OptiBIRTH study incorporates a multicentre cluster randomised
      trial in 15 hospital sites across three European countries. The trial was
      designed to test a complex intervention aimed at improving vaginal birth after
      caesarean section (VBAC) rates through increasing women's involvement in their
      care. Prior to developing a robust standardised model to conduct the health
      economic analysis, an analysis of a hypothetical cohort was performed to estimate
      the costs and health effects of VBAC compared to elective repeat caesarean
      delivery (ERCD) for low-risk women in four European countries. METHODS: A
      decision-analytic model was developed to estimate the costs and the health
      effects, measured using Quality Adjusted Life Years (QALYs), of VBAC compared
      with ERCD. A cost-effectiveness analysis for the period from confirmation of
      pregnancy to 6 weeks postpartum was performed for short-term consequences and
      during lifetime for long-term consequences, based on a hypothetical cohort of
      100,000 pregnant women in each of four different countries; Belgium, Germany,
      Ireland and Italy. A societal perspective was adopted. Where possible, transition
      probabilities, costs and health effects were adapted from national data obtained
      from the respective countries. Country-specific thresholds were used to determine
      the cost-effectiveness of VBAC compared to ERCD. Deterministic and probabilistic
      sensitivity analyses were conducted to examine the uncertainty of model
      assumptions. RESULTS: Within a 6-week time horizon, VBAC resulted in a reduction
      in costs, ranging from ?3,334,052 (Germany) to ?66,162,379 (Ireland), and gains
      in QALYs ranging from 6399 (Italy) to 7561 (Germany) per 100,000 women birthing
      in each country. Compared to ERCD, VBAC is the dominant strategy in all four
      countries. Applying a lifetime horizon, VBAC is dominant compared to ERCD in all
      countries except for Germany (probabilistic analysis, ICER: ?8609/QALY). In
      conclusion, compared to ERCD, VBAC remains cost-effective when using a lifetime
      time. CONCLUSIONS: In all four countries, VBAC was cost-effective compared to
      ERCD for low-risk women. This is important for health service managers,
      economists and policy makers concerned with maximising health benefits within
      limited and constrained resources.

PMID- 29642860
TI  - Atrophic inferior vena cava is a marker of chronicity of intra-filter and
      inferior vena cava thrombosis: based on CT findings.
AB  - BACKGROUND: A permanently indwelling filter in the inferior vena cava (IVC) may
      induce caval thrombosis, which could develop and evolve from an acute to a
      chronic phase. The differential diagnosis of acute and chronic thromboses
      determines the treatment strategy. The role of computed tomography (CT) in
      diagnosing acute and chronic intra-filter and IVC thromboses has not been well
      established. This retrospective study summarizes the CT signs that indicate acute
      and chronic phases of intra-filter and IVC thromboses. METHODS: This study
      included eight patients who developed a lower-extremity deep venous thrombosis
      (DVT) and were treated with intracaval filter placement as an alternative to
      anticoagulation and thrombolysis. During the follow-up, all patients developed an
      intra-filter thrombosis in the IVC confirmed by CT and/or CT venography (CTV).
      Demographic and CT data of all patients during the follow-up period were
      collected for analysis. RESULTS: All patients had normal-appearing IVCs prior to
      filter placement, as shown on trans-femoral venography. Eight filters (five
      TrapEase, three OptEase) were placed in the eight IVCs, respectively.
      Subsequently, IVC-CT or CTV revealed acute intra-filter or IVC thrombosis in all
      eight patients, manifesting as an intracaval filling defect and thickened IVC
      wall. Filter protrusion and secondary caval atrophy seen on CT indicated a
      chronically occluded IVC. CONCLUSIONS: IVC thrombosis may result from filter
      placement. The chronicity of caval thrombotic occlusion is likely to be
      associated with filter protrusion and secondary IVC atrophy revealed on CT scans.

PMID- 29642859
TI  - Identification of novel MITEs (miniature inverted-repeat transposable elements)
      in Coxiella burnetii: implications for protein and small RNA evolution.
AB  - BACKGROUND: Coxiella burnetii is a Gram-negative gammaproteobacterium and
      zoonotic agent of Q fever. C. burnetii's genome contains an abundance of
      pseudogenes and numerous selfish genetic elements. MITEs (miniature inverted
      repeat transposable elements) are non-autonomous transposons that occur in all
      domains of life and are thought to be insertion sequences (ISs) that have lost
      their transposase function. Like most transposable elements (TEs), MITEs are
      thought to play an active role in evolution by altering gene function and
      expression through insertion and deletion activities. However, information
      regarding bacterial MITEs is limited. RESULTS: We describe two MITE families
      discovered during research on small non-coding RNAs (sRNAs) of C. burnetii. Two
      sRNAs, Cbsr3 and Cbsr13, were found to originate from a novel MITE family, termed
      QMITE1. Another sRNA, CbsR16, was found to originate from a separate and novel
      MITE family, termed QMITE2. Members of each family occur ~ 50 times within the
      strains evaluated. QMITE1 is a typical MITE of 300-400 bp with short (2-3 nt)
      direct repeats (DRs) of variable sequence and is often found overlapping
      annotated open reading frames (ORFs). Additionally, QMITE1 elements possess sigma
      70 promoters and are transcriptionally active at several loci, potentially
      influencing expression of nearby genes. QMITE2 is smaller (150-190 bps), but has
      longer (7-11 nt) DRs of variable sequences and is mainly found in the 3'
      untranslated region of annotated ORFs and intergenic regions. QMITE2 contains a
      GTAG repetitive extragenic palindrome (REP) that serves as a target for IS1111 TE
      insertion. Both QMITE1 and QMITE2 display inter-strain linkage and sequence
      conservation, suggesting that they are adaptive and existed before divergence of
      C. burnetii strains. CONCLUSIONS: We have discovered two novel MITE families of
      C. burnetii. Our finding that MITEs serve as a source for sRNAs is novel. QMITE2
      has a unique structure and occurs in large or small versions with unique DRs that
      display linkage and sequence conservation between strains, allowing for tracking
      of genomic rearrangements. QMITE1 and QMITE2 copies are hypothesized to influence
      expression of neighboring genes involved in DNA repair and virulence through
      transcriptional interference and ribonuclease processing.

PMID- 29642861
TI  - Identification of methylation sites and signature genes with prognostic value for
      luminal breast cancer.
AB  - BACKGROUND: Robust and precise molecular prognostic predictors for luminal breast
      cancer are required. This study aimed to identify key methylation sites in
      luminal breast cancer, as well as precise molecular tools for predicting
      prognosis. METHODS: We compared methylation levels of normal and luminal breast
      cancer samples from The Cancer Genome Atlas dataset. The relationships among
      differentially methylated sites, corresponding mRNA expression levels and
      prognosis were further analysed. Differentially expressed genes in normal and
      cancerous samples were analysed, followed by the identification of prognostic
      signature genes. Samples were divided into low- and high-risk groups based on the
      signature genes. Prognoses of low- and high-risk groups were compared. The Gene
      Expression Omnibus dataset were used to validate signature genes for prognosis
      prediction. Prognosis of low- and high-risk groups in Luminal A and Luminal B
      samples from the TCGA and the Metabric cohort dataset were analyzed. We also
      analysed the correlation between clinical features of low- and high- risk groups
      as well as their differences in gene expression. RESULTS: Fourteen methylation
      sites were considered to be related to luminal breast cancer prognosis because
      their methylation levels, mRNA expression and prognoses were closely related to
      each other. The methylation level of SOSTDC1 was used to divide samples into hypo
      and hyper-methylation groups. We also identified an mRNA signature, comprising
      eight transcripts, ESCO2, PACSIN1, CDCA2, PIGR, PTN, RGMA, KLK4 and CENPA, which
      was used to divide samples into low- and high-risk groups. The low-risk group
      showed significantly better prognosis than the high-risk group. A correlation
      analysis revealed that the risk score was an independent prognostic factor. Low-
      and high- risk groups significantly correlated with the survival ratio in Luminal
      A samples, but not in Luminal B samples on the basis of the TCGA and the Metabric
      cohort dataset. Further functional annotation demonstrated that the
      differentially expressed genes were mainly involved in cell cycle and cancer
      progression. CONCLUSIONS: We identified several key methylation sites and an mRNA
      signature for predicting luminal breast cancer prognosis. The signature exhibited
      effective and precise prediction of prognosis and may serve as a prognostic and
      diagnostic marker for luminal breast cancer.

PMID- 29642862
TI  - Effectiveness and safety of moderate-intensity aerobic water exercise during
      pregnancy for reducing use of epidural analgesia during labor: protocol for a
      randomized clinical trial.
AB  - BACKGROUND: Epidural analgesia during labor can provide effective pain relief,
      but can also lead to adverse effects. The practice of moderate exercise during
      pregnancy is associated with an increased level of endorphins in the blood, and
      this could also provide pain relief during labor. Aerobic water exercises, rather
      than other forms of exercise, do not negatively impact articulations, reduce
      edema, blood pressure, and back pain, and increase diuresis. We propose a
      randomized controlled trial (RCT) to evaluate the effectiveness and safety of a
      moderate water exercise program during pregnancy on the need for epidural
      analgesia during labor. METHODS: A multi-center, parallel, randomized, evaluator
      blinded, controlled trial in a primary care setting. We will randomised 320
      pregnant women (14 to 20 weeks gestation) who have low risk of complications to a
      moderate water exercise program or usual care. DISCUSSION: The findings of this
      research will contribute toward understanding of the effects of a physical
      exercise program on pain and the need for analgesia during labor. TRIAL
      REGISTRATION: ISRCTN Registry identifier: 14097513 register on 04 September 2017.
      Retrospectively registered.

PMID- 29642863
TI  - Risk of seizures after immunization in children with epilepsy: a risk interval
      analysis.
AB  - BACKGROUND: In children with epilepsy, fever and infection can trigger seizures.
      Immunization can also induce inflammation and fever, which could theoretically
      trigger a seizure. The risk of seizure after immunization in children with pre
      existing epilepsy is not known. The study objective was to determine the risk of
      medically attended seizure after immunization in children with epilepsy < 7 years
      of age. METHODS: We conducted a retrospective study of children < 7 years of age
      with epilepsy in Nova Scotia, Canada from 2010 to 2014. Hospitalizations,
      emergency visits, unscheduled clinic visits, and telephone calls for seizures
      were extracted from medical records. Immunization records were obtained from
      family physicians and Public Health with informed consent. We conducted a risk
      interval analysis to estimate the relative risk (RR) of seizure during risk
      periods 0-14, 0-2, and 5-14 days post-immunization versus a control period 21-83
      days post-immunization. RESULTS: There were 302 children with epilepsy who were
      eligible for the study. Immunization records were retrieved on 147 patients
      (49%), of whom 80 (54%) had one or more immunizations between the epilepsy
      diagnosis date and age 7 years. These 80 children had 161 immunization visits and
      197 medically attended seizures. Children with immunizations had more seizures
      than either those with no immunizations or those with no records (mean 2.5 versus
      0.7 versus 0.9, p < 0.001). The risk of medically attended seizure was not
      increased 0-14 days after any vaccine (RR = 1.1, 95% confidence interval (CI):
      0.5-2.8) or 0-2 days after inactivated vaccines (RR = 0.9, 95% CI: 0.1-7.1)
      versus 21-83 days post-immunization. No seizure events occurred 5-14 days after
      live vaccines. CONCLUSIONS: Children with epilepsy do not appear to be at
      increased risk of medically attended seizure following immunization. These
      findings suggest that immunization is safe in children with epilepsy, with
      benefits outweighing risks.

PMID- 29642864
TI  - Development of a novel motivational interviewing (MI) informed peer-support
      intervention to support mothers to breastfeed for longer.
AB  - BACKGROUND: Many women in the UK stop breastfeeding before they would like to,
      and earlier than is recommended by the World Health Organization (WHO). Given the
      potential health benefits for mother and baby, new ways of supporting women to
      breastfeed for longer are required. The purpose of this study was to develop and
      characterise a novel Motivational Interviewing (MI) informed breastfeeding peer
      support intervention. METHODS: Qualitative interviews with health professionals
      and service providers (n = 14), and focus groups with mothers (n = 14), fathers
      (n = 3), and breastfeeding peer-supporters (n = 15) were carried out to
      understand experiences of breastfeeding peer-support and identify intervention
      options. Data were audio-recorded, transcribed, and analysed thematically.
      Consultation took place with a combined professional and lay Stakeholder Group (n
      = 23). The Behaviour Change Wheel (BCW) guided intervention development process
      used the findings of the qualitative research and stakeholder consultation,
      alongside evidence from existing literature, to identify: the target behaviour to
      be changed; sources of this behaviour based on the Capability, Opportunity and
      Motivation (COM-B) model; intervention functions that could alter this behaviour;
      and; mode of delivery for the intervention. Behaviour change techniques included
      in the intervention were categorised using the Behaviour Change Technique
      Taxonomy Version 1 (BCTTv1). RESULTS: Building knowledge, skills, confidence, and
      providing social support were perceived to be key functions of breastfeeding peer
      support interventions that aim to decrease early discontinuation of
      breastfeeding. These features of breastfeeding peer-support mapped onto the BCW
      education, training, modelling and environmental restructuring intervention
      functions. Behaviour change techniques (BCTTv1) included social support, problem
      solving, and goal setting. The intervention included important inter-personal
      relational features (e.g. trust, honesty, kindness), and the BCTTv1 needed
      adaptation to incorporate this. CONCLUSIONS: The MI-informed breastfeeding peer
      support intervention developed using this systematic and user-informed approach
      has a clear theoretical basis and well-described behaviour change techniques. The
      process described could be useful in developing other complex interventions that
      incorporate peer-support and/or MI.

PMID- 29642865
TI  - Serum leucine-rich alpha-2-glycoprotein-1 with fucosylated triantennary N-glycan:
      a novel colorectal cancer marker.
AB  - BACKGROUND: Carcinoembryonic antigen (CEA) and carbohydrate antigen (CA)19-9 are
      used in clinical practice as tumor markers to diagnose or monitor colorectal
      cancer (CRC) patients, However, their specificities and sensitivities are not
      ideal, and novel alternatives are needed. In this study, mass spectrometry was
      used to search for screening markers, focusing on glycan alterations of
      glycoproteins in the sera of CRC patients. METHODS: Glycopeptides were prepared
      from serum glycoproteins separated from blood samples of 80 CRC patients and 50
      healthy volunteers, and their levels were measured by liquid chromatography time
      of flight mass spectrometry (LC-TOF-MS). RESULTS: Leucine-rich alpha-2
      glycoprotein-1 with fucosylated triantennary N-glycan (LRG-FTG) was identified as
      CRC marker after evaluating 30,000 candidate glycopeptide peaks. The average LRG
      FTG level in CRC patients (1.25 +/- 0.973 U/mL) was much higher than that in
      healthy volunteers (0.496 +/- 0.433 U/mL, P < 10- 10), and its sensitivity and
      specificity exceeded those of CA19-9. The combination of CEA and LRG-FTG showed a
      complementary effect and had better sensitivity (84%), specificity (90%), and AUC
      (0.91 by ROC analysis) than each marker alone or any other previously reported
      marker. LRG-FTG alone or combined with CEA also corresponded well with patient
      response to treatment. CONCLUSIONS: We identified LRG-FTG as a new CRC marker,
      with a sensitivity and specificity exceeding CA19-9. The combination of LRG-FTG
      and CEA showed much higher sensitivity and specificity than each marker alone.
      Further validation beyond this initial exploratory cohort is warranted.

PMID- 29642866
TI  - Using photo-elicitation to understand reasons for repeated self-harm: a
      qualitative study.
AB  - BACKGROUND: Reasons for self-harm are not well understood. One of the reasons for
      this is that first-hand accounts are usually elicited using traditional interview
      and questionnaire methods. This study aims to explore the acceptability of using
      an approach (photo-elicitation) that does not rely on solely verbal or written
      techniques, and to make a preliminary assessment of whether people can usefully
      employ images to support a discussion about the reasons why they self-harm.
      METHOD: Interviews with eight participants using photo elicitation, a method in
      which photographs produced by the participant are used as a stimulus and guide
      within the interview. RESULTS: Participants responded positively to using images
      to support a discussion about their self-harm and readily incorporated images in
      the interview. Four main themes were identified representing negative and
      positive or adaptive purposes of self-harm: self-harm as a response to distress,
      self-harm to achieve mastery, self-harm as protective and self-harm as a language
      or form of communication. CONCLUSIONS: Employing this novel approach was useful
      in broadening our understanding of self-harm.

PMID- 29642867
TI  - Antiproliferative activities and phenolic acid content of water and ethanolic
      extracts of the powdered formula of Houttuynia cordata Thunb. fermented broth and
      Phyllanthus emblica Linn. fruit.
AB  - BACKGROUND: Houttuynia cordata Thunb. and Phyllanthus emblica Linn. are native
      plants with medicinal and nutritive significance in Asia. The present study was
      aimed at evaluating antiproliferative effects on human cancer cell lines and
      identifying the phenolic acid composition of water and ethanolic extracts of the
      powdered formula of H. cordata fermented broth and P. emblica fruit. METHODS:
      Anticancer activity of the extracts was evaluated against HeLa, HT29, HCT116,
      MCF7 and Jurkat cells using an MTT assay and flow cytometric analysis of
      apoptosis induction and cell cycle arrest. Reverse phase HPLC was exploited for
      identification and quantification of some phenolic acids. RESULTS: MTT assay
      showed that both water and ethanolic extracts significantly decreased the
      viability of cancer cells in a dose- and time-dependent fashion. Based on the
      IC50 values, ethanolic extract (IC50 values = 0.12-0.65 mg/mL) was more cytotoxic
      than water extract (IC50 values = 0.22-0.85 mg/mL) and Jurkat cells were the most
      sensitive to both extracts (IC50 values = 0.12-0.69 mg/mL). The underlying
      mechanism for antiproliferative activity was apoptosis induction, especially in
      HT29, HCT116, MCF7 and Jurkat cells. HT29 cells were the most sensitive to
      extract-induced apoptosis. Ethanolic extract was more effective at inducing
      apoptosis than water extract. Moreover, cell cycle arrest was found to be another
      mechanism behind growth inhibition in Jurkat and HCT116 cells. However, these
      extracts were relatively less toxic to non-cancer Vero cells. HPLC analysis
      demonstrated that the powder mix extracts contained seven identified phenolic
      acids namely gallic, p-hydroxybenzoic, vanillic, syringic, p-coumaric, ferulic
      and sinapinic acids, where p-coumaric acid was detected in the highest
      concentration followed by ferulic acid. CONCLUSION: Overall, the results of this
      study suggest the powdered formula of H. cordata fermented broth and P. emblica
      fruit as an alternative medicine for cancer prevention and treatment.

PMID- 29642868
TI  - Adaptation of an evidence-based postpartum depression intervention: feasibility
      and acceptability of mothers and babies 1-on-1.
AB  - BACKGROUND: Mothers and Babies (MB) is a cognitive-behavioral intervention with
      demonstrated efficacy in reducing depressive symptoms and preventing depressive
      episodes among perinatal women when delivered in a group format by mental health
      professionals. Study aims were to describe the adaptation of MB into a 1-on-1
      modality (MB 1-on-1) and provide data on the adapted intervention's acceptability
      and feasibility. METHODS: Seventy-five home visitors trained on MB 1-on-1
      delivered the 15-session intervention to 1-2 clients. Client acceptability data
      assessed intervention enjoyment, comprehension, and usefulness. Home visitor
      feasibility and acceptability data measured amount of intervention material
      delivered, client comprehension, and client engagement. RESULTS: Home visitors
      were all female with 8.8 years of experience on average. 117 clients completed
      acceptability surveys. Average client age was 21.9 years and 41% were pregnant.
      Home visitors completely covered 87.9% of sessions and reported clients totally
      understood MB material 82.5% of the time across sessions, although variability
      was found in comprehension across modules. 82.0% of clients found MB 1-on-1
      enjoyable and 91.6% said they totally understood sessions, when averaged across
      sessions. Clients enjoyed content on noticing one's mood and pleasant activities.
      Implementation challenges were client engagement, facilitating completion of
      personal projects, and difficulty shifting between didactic and interactive
      activities. CONCLUSIONS: Clients found MB 1-on-1 to be enjoyable, easily
      understood, and useful. Home visitors reported excellent implementation fidelity
      and felt clients understood MB material. A refined 12-session version of MB 1-on
      1 should be examined for its effectiveness in reducing depressive symptoms, given
      encouraging feasibility and acceptability data.

PMID- 29642870
TI  - Correction to: An Arabidopsis introgression zone studied at high spatio-temporal
      resolution: interglacial and multiple genetic contact exemplified using whole
      nuclear and plastid genomes.
AB  - ?: Upon publication of the original article [1], the authors had flagged that
      there was an error in Fig. 1c, as the key in this figure was displaying
      incorrectly. The colours had not displayed in the key in the final published
      article, and instead appear as plain white.

PMID- 29642869
TI  - Characteristics of human encounters and social mixing patterns relevant to
      infectious diseases spread by close contact: a survey in Southwest Uganda.
AB  - BACKGROUND: Quantification of human interactions relevant to infectious disease
      transmission through social contact is central to predict disease dynamics, yet
      data from low-resource settings remain scarce. METHODS: We undertook a social
      contact survey in rural Uganda, whereby participants were asked to recall details
      about the frequency, type, and socio-demographic characteristics of any
      conversational encounter that lasted for >=5 min (henceforth defined as
      'contacts') during the previous day. An estimate of the number of 'casual
      contacts' (i.e. < 5 min) was also obtained. RESULTS: In total, 566 individuals
      were included in the study. On average participants reported having routine
      contact with 7.2 individuals (range 1-25). Children aged 5-14 years had the
      highest frequency of contacts and the elderly (>=65 years) the fewest (P <
      0.001). A strong age-assortative pattern was seen, particularly outside the
      household and increasingly so for contacts occurring further away from home.
      Adults aged 25-64 years tended to travel more often and further than others, and
      males travelled more frequently than females. CONCLUSION: Our study provides
      detailed information on contact patterns and their spatial characteristics in an
      African setting. It therefore fills an important knowledge gap that will help
      more accurately predict transmission dynamics and the impact of control
      strategies in such areas.

PMID- 29642871
TI  - Quality of internet-based decision aids for shoulder arthritis: what are patients
      reading?
AB  - BACKGROUND: The objective of this study was to assess the source, quality,
      accuracy, and completeness of Internet-based information for shoulder arthritis.
      METHODS: A web search was performed using three common Internet search engines
      and the top 50 sites from each search were analyzed. Information sources were
      categorized into academic, commercial, non-profit, and physician sites.
      Information quality was measured using the Health On the Net (HON) Foundation
      principles, content accuracy by counting factual errors and completeness using a
      custom template. RESULTS: After removal of duplicates and sites that did not
      provide an overview of shoulder arthritis, 49 websites remained for analysis. The
      majority of sites were from commercial (n = 16, 33%) and physician (n = 16, 33%)
      sources. An additional 12 sites (24%) were from an academic institution and five
      sites (10%) were from a non-profit organization. Commercial sites had the highest
      number of errors, with a five-fold likelihood of containing an error compared to
      an academic site. Non-profit sites had the highest HON scores, with an average of
      9.6 points on a 16-point scale. The completeness score was highest for academic
      sites, with an average score of 19.2 +/- 6.7 (maximum score of 49 points); other
      information sources had lower scores (commercial, 15.2 +/- 2.9; non-profit, 18.7
      +/- 6.8; physician, 16.6 +/- 6.3). CONCLUSIONS: Patient information on the
      Internet regarding shoulder arthritis is of mixed accuracy, quality, and
      completeness. Surgeons should actively direct patients to higher-quality Internet
      sources.

PMID- 29642872
TI  - Karyotype diversity and 2C DNA content in species of the Caesalpinia group.
AB  - BACKGROUND: The Leguminosae family is the third-largest family of angiosperms,
      and Caesalpinioideae is its second-largest subfamily. A great number of species
      (approximately 205) are found in the Caesalpinia group within this subfamily;
      together with these species' phenotypic plasticity and the similarities in their
      morphological descriptors, make this a complex group for taxonomic and
      phylogenetic studies. The objective of the present work was to evaluate the
      karyotypic diversity and the 2C DNA content variation in 10 species of the
      Caesalpinia group, representing six genera: Paubrasilia, Caesalpinia, Cenostigma,
      Poincianella, Erythrostemon and Libidibia. The GC-rich heterochromatin and 45S
      rDNA sites (which are used as chromosome markers) were located to evaluate the
      karyotype diversity in the clade. The variation in the 2C DNA content was
      determined through flow cytometry. RESULTS: The fluorochrome banding indicated
      that the chromomycin A3+/4',6-diamidino-2-phenylindole- blocks were exclusively
      in the terminal regions of the chromosomes, coinciding with 45S rDNA sites in all
      analyzed species. Physical mapping of the species (through fluorescence in situ
      hybridization) revealed variation in the size of the hybridization signals and in
      the number and distribution of the 45S rDNA sites. All hybridization sites were
      in the terminal regions of the chromosomes. In addition, all species had a
      hybridization site in the fourth chromosome pair. The 2C DNA content ranged from
      1.54 pg in Erythrostemon calycina to 2.82 pg in the Paubrasilia echinata large
      leaf variant. The Pa. echinata small-leaf variant was isolated from the other
      leaf variants through Scoot-Knott clustering. CONCLUSIONS: The chromosome
      diversity and the variation in the 2C DNA content reinforce that the actual
      taxonomy and clustering of the analyzed taxa requires more genera that were
      previously proposed. This fact indicates that taxonomy, phylogeny and
      cytoevolutionary inference related to the complex Caesalpinia group have to be
      done through integrative evaluation.

PMID- 29642873
TI  - Bexarotene inhibits the viability of non-small cell lung cancer cells via
      slc10a2/PPARgamma/PTEN/mTOR signaling pathway.
AB  - BACKGROUND: Thirty to 40 % of non-small cell lung cancer (NSCLC) patients
      developed higher hypertriglyceridemia in the process of treatment with
      bexarotene. And bioinformatics studies discovered that the expression of slc10a2
      was increased in high-grade hypertriglyceridemia patients. So, we will explore
      the mechanism which may involve in this process. METHODS: We constructed slc10a2
      overexpressed A549 cells and H1299 cells as cell models, normal A549 cells and
      H1299 cells as control. Then we explored the effects of slc10a2 on A549 cells and
      H1299 cells behaviors, including proliferation, invasion and apoptosis. The
      expression of apoptotic related genes and anti-cancer genes also been detected.
      RESULTS: We found that the proliferation and migration were inhibited and the
      apoptosis of NSCLC cells was accelerated by bexarotene. In addition,
      overexpressed slc10a2 in NSCLC cells can further suppress the proliferation and
      migration, and promote apoptosis under the treatment of bexarotene. On the
      contrary, the opposite results were obtained after slc10a2 gene was silenced in
      NSCLC cells treated with bexarotene. Moreover, the expression of caspase 3,
      caspase 7, PTEN, P21, P53, LKB1, TSC2 were increased and the expression of Bcl-2,
      cyclin D1, c-FLIP were declined in NSCLC cells and slc10a2 overexpressed NSCLC
      cells with the treatment of bexarotene, and the opposite situations were seen
      after slc10a2 gene was silenced in NSCLC cells. The further studies revealed the
      increased expression of slc10a2 activated the expression of peroxisome
      proliferator-activated receptor gamma (PPARgamma), then up-regulated PTEN
      expression and down-regulated mTOR expression. CONCLUSION: These results suggest
      that bexarotene inhibits the viability of lung cancer cells via
      slc10a2/PPARgamma/PTEN/mTOR signaling pathway.

PMID- 29642874
TI  - Pilot evaluation of a second-generation electronic pill box for adherence to
      Bedaquiline and antiretroviral therapy in drug-resistant TB/HIV co-infected
      patients in KwaZulu-Natal, South Africa.
AB  - BACKGROUND: The introduction of Bedaquiline, the first new antimycobacterial drug
      in over 40 years, has highlighted the critical importance of medication adherence
      in drug-resistant tuberculosis (DR-TB) treatment to prevent amplified drug
      resistance and derive sustained benefit. Real-time electronic dose monitoring
      (EDM) accurately measures adherence and allows for titration of adherence support
      for anti-retroviral therapy (ART). The goal of this study was to evaluate the
      accuracy and acceptability of a next-generation electronic pillbox (Wisepill
      RT2000) for Bedaquiline-containing TB regimens. METHODS: Eligible patients were
      DR-TB/HIV co-infected adults hospitalized for the initiation of Bedaquiline
      containing treatment regimens in KwaZulu-Natal, South Africa. A one-way crossover
      design was used to evaluate levels of adherence and patient acceptance of EDM.
      Each patient was given a Wisepill device which was filled with ART, Levofloxacin
      or Bedaquiline over three consecutive weeks. Medication adherence was measured
      using Wisepill counts, patient-reported seven-day recall, and weekly pill count.
      An open-ended qualitative questionnaire at the end of the study evaluated
      participant acceptability of the Wisepill device. RESULTS: We enrolled 21 DR
      TB/HIV co-infected inpatients admitted for the initiation of Bedaquiline from
      August through September 2016. In aggregate patients were similarly adherent to
      Bedaquiline (100%) compared to Levofloxacin (100%) and ART (98.9%) by pill count.
      Wisepill was more sensitive (100%) compared to seven-day recall (0%) in detecting
      non-adherence events (p = 0.02). Patients reported positive experiences with
      Wisepill and expressed willingness to use the device during a full course of DR
      TB treatment. There were no concerns about stigma, confidentiality, or remote
      monitoring. CONCLUSION: In this pilot study patients were highly adherent to
      Bedaquiline by all adherence measures. However, there was lower adherence to ART
      by pill count and Wisepill suggesting a possible challenge for adherence with
      ART. The use of EDM identified significantly more missed doses than seven-day
      recall. Wisepill was highly acceptable to DR-TB/HIV patients in South Africa, and
      is a promising modality to support and monitor medication adherence in complex
      treatment regimens.

PMID- 29642875
TI  - Comparing the performance of circulating cathodic antigen and Kato-Katz
      techniques in evaluating Schistosoma mansoni infection in areas with low
      prevalence in selected counties of Kenya: a cross-sectional study.
AB  - BACKGROUND: Kato-Katz technique has been the mainstay test in Schistosoma mansoni
      diagnosis in endemic areas. However, recent studies have documented its poor
      sensitivity in evaluating Schistosoma mansoni infection especially in areas with
      lower rates of transmission. It's the primary diagnostic tool in monitoring
      impact of the Kenya national school based deworming program on infection
      transmission, but there is need to consider a more sensitive technique as the
      prevalence reduces. Therefore, this study explored the relationship between
      results of the stool-based Kato-Katz technique with urine-based point-of-care
      circulating cathodic antigen (POC-CCA) test in view to inform decision-making by
      the program in changing from Kato-Katz to POC-CCA test. METHODS: We used two
      cross-sectional surveys conducted pre- and post- mass drug administration (MDA)
      using praziquantel in a representative random sample of children from 18 schools
      across 11 counties. A total of 1944 children were randomly sampled for the study.
      Stool and urine samples were tested for S. mansoni infection using Kato-Katz and
      POC-CCA methods, respectively. S. mansoni prevalence using each technique was
      calculated and 95% confidence intervals obtained using binomial regression model.
      Specificity (Sp) and sensitivity (Sn) were determined using 2 * 2 contingency
      tables and compared using the McNemar's chi-square test. RESULTS: A total of 1899
      and 1878 children were surveyed at pre- and post-treatment respectively. S.
      mansoni infection prevalence was 26.5 and 21.4% during pre- and post-treatment
      respectively using POC-CCA test, and 4.9 and 1.5% for pre- and post-treatment
      respectively using Kato-Katz technique. Taking POC-CCA as the gold standard, Kato
      Katz was found to have significantly lower sensitivity both at pre- and post
      treatment, Sn = 12.5% and Sn = 5.2% respectively, McNemar test chi2m = 782.0, p <
      0.001. In overall, the results showed a slight/poor agreement between the two
      methods, kappa index (k) = 0.11, p < 0.001, inter-rater agreement = 77.1%.
      CONCLUSIONS: Results showed POC-CCA technique as an effective, sensitive and
      accurate screening tool for Schistosoma mansoni infection in areas of low
      prevalence. It was up to 14-fold accurate than Kato-Katz which had extremely
      inadequate sensitivity. We recommend usage of POC-CCA alongside Kato-Katz
      examinations by Schistosomiasis control programs in low prevalence areas.

PMID- 29642876
TI  - Smoking among immigrant groups in metropolitan France: prevalence levels, male-to
      female ratios and educational gradients.
AB  - BACKGROUND: Although the French population comprises large and diverse immigrant
      groups, there is little research on smoking disparities by geographical origin.
      The aim of this study is to investigate in this country smoking among immigrants
      born in either north Africa, sub-Saharan Africa or French overseas departements.
      METHODS: The data originate from the 2010 Health Barometer survey representative
      of metropolitan France. The subsample of 20,211 individuals aged 18-70 years
      (born either in metropolitan France or in the above-mentioned geographical
      regions) was analysed using logistic regression. RESULTS: Both immigrants from
      sub-Saharan Africa and immigrants from overseas departements were protected from
      smoking compared to the reference population, and the former had a distinctive
      strongly reversed educational gradient in both genders. Returned former settlers
      from the French colonies in North Africa (repatriates) had the highest smoking
      levels. Natives from the Maghreb (Maghrebins) showed considerable gender
      discordance, with men having both a higher prevalence (borderline significance)
      and a reversed gradient and women having lower prevalence than the reference
      population. CONCLUSION: Immigrants from regions of the world in stage 1 of the
      cigarette epidemic had relatively low smoking levels and those from regions in
      stage 2 had relatively high smoking levels. Some groups had a profile
      characteristic of late phases of the cigarette epidemic, and others, some of
      which long-standing residents, seemed to be positioned at its early stages. The
      situation for Maghrebins reflected the enduring influence of gendered norms post
      migration. Based on their educational gradients, immigrants from overseas
      departements (particularly men) and Maghrebin women may be at risk of losing
      their particularly low prevalence. Immigrants from sub-Saharan Africa could
      retain it. In-depth analysis of smoking profiles of immigrants' groups is
      essential for a better targeting of smoking prevention and cessation programs.

PMID- 29642877
TI  - Standardisation framework for the Maudsley staging method for treatment
      resistance in depression.
AB  - BACKGROUND: Treatment-resistant depression (TRD) is a serious and relatively
      common clinical condition. Lack of consensus on defining and staging TRD remains
      one of the main barriers to understanding TRD and approaches to intervention. The
      Maudsley Staging Method (MSM) is the first multidimensional model developed to
      define and stage treatment-resistance in "unipolar depression". The model is
      being used increasingly in treatment and epidemiological studies of TRD and has
      the potential to support consensus. Yet, standardised methods for rating the MSM
      have not been described adequately. The aim of this report is to present
      standardised approaches for rating or completing the MSM. METHOD: Based on the
      initial development of the MSM and a narrative review of the literature, the
      developers of the MSM provide explicit guidance on how the three dimensions of
      the MSM--treatment failure, severity of depressive episode and duration of
      depressive episode-- may be rated. RESULT: The core dimension of the MSM,
      treatment failure, may be assessed using the Maudsley Treatment Inventory (MTI),
      a new method developed for the purposes of completing the MSM. The MTI consists
      of a relatively comprehensive list of medications with options for rating doses
      and provisions treatment for multiple episodes. The second dimension, severity of
      symptoms, may be assessed using simple instruments such as the Clinical Global
      Impression, the Psychiatric Status Rating or checklist from a standard diagnostic
      checklist. The standardisation also provides a simple rating scale for scoring
      the third dimension, duration of depressive episode. CONCLUSION: The approaches
      provided should have clinical and research utility in staging TRD. However, in
      proposing this model, we are fully cognisant that until the pathophysiology of
      depression is better understood, staging methods can only be tentative
      approximations. Future developments should attempt to incorporate other
      biological/ pathophysiological dimensions for staging.

PMID- 29642878
TI  - The problem of suicide among Amerindians in Camopi-Trois Sauts, French Guiana
      2008-2015.
AB  - BACKGROUND: Suicide within the Amerindian community of Camopi (1741 inhabitants)
      in French Guiana has been an increasing problem widely reported in the media
      leading the French Government to mandate a parliamentary mission to investigate
      the matter. The purpose of the study was to describe this phenomenon and identify
      factors associated with suicide attempts. METHODS: A retrospective observational
      study was conducted from the health centers' medical records. All suicide
      attempts and suicides committed between 2008 and 2015 by Amerindians living in
      Camopi and Trois Sauts were compiled. Contextual factors and suicide
      representations were also analyzed. RESULTS: During the study period, the annual
      attempted suicide rate and the suicide rate were higher in the last 3 years. The
      overall annual rate was equal to 6.9/1741 or 396 per 100, 000 inhabitants for
      attempted suicide and 172 per 100,000 inhabitants for suicide, which is more than
      10 times higher than the suicide rate in mainland France. The mortality rate was
      30.4% versus 8.2% in mainland France. The 10-20 year-old age group represented
      70% of suicide deaths. There was no significant difference between genders. A
      recent death and interpersonal conflict were the main stressful life events
      reported by respondents (55 and 52%, respectively). Alcohol addiction (30% of the
      respondents) was associated with suicide attempts under the influence of alcohol
      (p = 0.03). Repetition of suicide attempts was associated with cannabis
      consumption (p = 0.03). Depression was reported among 45% of the respondents. A
      third of respondents reported having been abused during their childhood. Over
      half of respondents reported that their suicide attempt was motivated by a spirit
      (58%). CONCLUSIONS: Despite limitations due to the small population size and
      limited time frame, this is the first study to describe the epidemiology of
      suicide among Amerindians living in Camopi. In contrast with other French
      territories, the suicide rate was very high, the sex ratio was balanced and
      younger age groups were most affected.

PMID- 29642879
TI  - Correlates of healthy life expectancy in low- and lower-middle-income countries.
AB  - BACKGROUND: Healthy life expectancy (HALE) at birth is an important indicator of
      health status and quality of life of a country's population. However, little is
      known about the determinants of HALE as yet globally or even country-specific
      level. Thus, we examined the factors that are associated with HALE at birth in
      low- and lower-middle-income countries. METHODS: In accordance with the World
      Bank (WB) classification seventy-nine low- and lower-middle-income countries were
      selected for the study. Data on HALE, demographic, socioeconomic, social
      structural, health, and environmental factors from several reliable sources, such
      as the World Health Organization, the United Nations Development Program,
      Population Reference Bureau, WB, Heritage Foundation, Transparency International,
      Freedom House, and International Center for Prison Studies were obtained as
      selected countries. Descriptive statistics, correlation analysis, and regression
      analysis were performed to reach the research objectives. RESULTS: The lowest and
      highest HALE were observed in Sierra Leone (44.40 years) and in Sri Lanka (67.00
      years), respectively. The mean years of schooling, total fertility rate (TFR),
      physician density, gross national income per capita, health expenditure, economic
      freedom, carbon dioxide emission rate, freedom of the press, corruption
      perceptions index, prison population rate, and achieving a level of health
      related millennium development goals (MDGs) were revealed as the correlates of
      HALE. Among all the correlates, the mean years of schooling, TFR, freedom of the
      press, and achieving a level of health-related MDGs were found to be the most
      influential factors. CONCLUSION: To increase the HALE in low- and lower-middle
      income countries, we suggest that TFR is to be reduced as well as to increase the
      mean years of schooling, freedom of the press, and the achievement of a level of
      health-related MDGs.

PMID- 29642880
TI  - Prevalence of latent tuberculosis infection among coal workers' pneumoconiosis
      patients in China: a cross-sectional study.
AB  - BACKGROUND: Little is known about the prevalence of latent tuberculosis infection
      (LTBI) among coal workers' pneumoconiosis (CWP) patients. To estimate the
      prevalence of LTBI and identify its associated risk factors among CWP patients.
      METHODS: A cross-sectional study was conducted to assess the prevalence of LTBI.
      Participants were screened for active TB or a history of TB by X-ray and those
      that underwent QuantiFERON-TB Gold In-Tube (QFT) test. A standardized
      questionnaire was completed and risk factors were assessed for acquiring TB. Log
      binomial regression was used to estimate the LTBI prevalence ratio (PR) in
      relation to risk factors. RESULTS: Of 244 individuals with CWP (median age 67
      years; all male), 162 (66.4%) were QFT positive. In Multivariate analysis, poor
      workplace ventilation (adjusted prevalence ratio [APR] = 1.26) and intake of
      fruits regularly (>=4 days of every week) (APR = 0.81) (all p < 0.05) were
      associated with a decreased risk of QFT. CONCLUSIONS: This study showed a high
      prevalence of LTBI among individuals with CWP in China. Poor workplace
      ventilation may be an important contributing factor for LTBI. Regular monitoring
      and dust control measures need to be improved in workplaces to ensure the safety
      of workers. Moreover, intake of fruits regularly may be a protective factor for
      LTBI. However, the effect of fruits should be further studied.

PMID- 29642881
TI  - Antiplasmodial and trypanocidal activity of violacein and deoxyviolacein produced
      from synthetic operons.
AB  - BACKGROUND: Violacein is a deep violet compound that is produced by a number of
      bacterial species. It is synthesized from tryptophan by a pathway that involves
      the sequential action of 5 different enzymes (encoded by genes vioA to vioE).
      Violacein has antibacterial, antiparasitic, and antiviral activities, and also
      has the potential of inducing apoptosis in certain cancer cells. RESULTS: Here,
      we describe the construction of a series of plasmids harboring the complete or
      partial violacein biosynthesis operon and their use to enable production of
      violacein and deoxyviolacein in E.coli. We performed in vitro assays to determine
      the biological activity of these compounds against Plasmodium, Trypanosoma, and
      mammalian cells. We found that, while deoxyviolacein has a lower activity against
      parasites than violacein, its toxicity to mammalian cells is insignificant
      compared to that of violacein. CONCLUSIONS: We constructed E. coli strains
      capable of producing biologically active violacein and related compounds, and
      propose that deoxyviolacein might be a useful starting compound for the
      development of antiparasite drugs.

PMID- 29642882
TI  - Assessing the healthcare resource use associated with inappropriate prescribing
      of inhaled corticosteroids for people with chronic obstructive pulmonary disease
      (COPD) in GOLD groups A or B: an observational study using the Clinical Practice
      Research Datalink (CPRD).
AB  - BACKGROUND: Recent recommendations from the Global Initiative for Chronic
      Obstructive Lung Disease (GOLD) position inhaled corticosteroids (ICS) for use in
      chronic obstructive pulmonary disease (COPD) patients experiencing exacerbations
      (>= 2 or >= 1 requiring hospitalisation); i.e. GOLD groups C and D. However, it
      is known that ICS is frequently prescribed for patients with less severe COPD.
      Potential drivers of inappropriate ICS use may be historical clinical guidance or
      a belief among physicians that intervening early with ICS would improve outcomes
      and reduce resource use. The objective of this study was to compare healthcare
      resource use in the UK for COPD patients in GOLD groups A and B (0 or 1
      exacerbation not resulting in hospitalisation) who have either been prescribed an
      ICS-containing regimen or a non-ICS-containing regimen. METHODS: Linked data from
      the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics
      (HES) database were used. For the study period (1 July 2005 to 30 June 2015) a
      total 4009 patients met the inclusion criteria; 1745 receiving ICS-containing
      therapy and 2264 receiving non-ICS therapy. Treatment groups were propensity
      score-matched to account for potential confounders in the decision to prescribe
      ICS, leaving 1739 patients in both treatment arms. Resource use was assessed in
      terms of frequency of healthcare practitioner (HCP) interactions and rescue
      therapy prescribing. Treatment acquisition costs were not assessed. RESULTS:
      Results showed no benefit associated with the addition of ICS, with numerically
      higher all-cause HCP interactions (72,802 versus 69,136; adjusted relative rate:
      1.07 [p = 0.061]) and rescue therapy prescriptions (24,063 versus 21,163;
      adjusted relative rate: 1.05 [p = 0.212]) for the ICS-containing group compared
      to the non-ICS group. Rate ratios favoured the non-ICS group for eight of nine
      outcomes assessed. Outcomes were similar for subgroup analyses surrounding
      potential influential parameters, including patients with poorer lung function
      (FEV1 <  50% predicted), one prior exacerbation or elevated blood eosinophils.
      CONCLUSIONS: These data suggest that ICS use in GOLD A and B COPD patients is not
      associated with a benefit in terms of healthcare resource use compared to non-ICS
      bronchodilator-based therapy; using ICS according to GOLD recommendations may
      offer an opportunity for improving patient care and reducing resource use.

PMID- 29642883
TI  - Associations between ideational variables and bed net use in Madagascar, Mali,
      and Nigeria.
AB  - BACKGROUND: The use of insecticide-treated bed nets (ITNs) is crucial to the
      prevention, control, and elimination of malaria. Using household surveys
      conducted in 2014-2015 by the Health Communication Capacity Collaborative project
      in Madagascar, Mali, and Nigeria, we compared a model of psychosocial influence,
      called Ideation, to examine how malaria-related variables influence individual
      and household bed net use in each of these countries. Evaluations of non-malaria
      programs have confirmed the value of the ideational approach, but it is
      infrequently used to guide malaria interventions. The study objective was to
      examine how well this model could identify potentially effective malaria
      prevention approaches in different contexts. METHODS: Sampling and survey designs
      were similar across countries. A multi-stage random sampling process selected
      female caregivers with at least one child under 5 years of age for interviews.
      Additional data were collected from household heads about bed net use and other
      characteristics of household members. The caregiver survey measured psychosocial
      variables that were subjected to bivariate and multivariate analysis to identify
      significant ideational variables related to bed net use. RESULTS: In all three
      countries, children and adolescents over five were less likely to sleep under a
      net compared to children under five (OR = 0.441 in Madagascar, 0.332 in Mali,
      0.502 in Nigeria). Adults were less likely to sleep under a net compared to
      children under five in Mali (OR = 0.374) and Nigeria (OR = 0.448), but not
      Madagascar. In all countries, the odds of bed net use were lower in larger
      compared to smaller households (OR = 0.452 in Madagascar and OR = 0.529 in
      Nigeria for households with 5 or 6 members compared to those with less than 5;
      and OR = 0.831 in Mali for larger compared to smaller households). Of 14 common
      ideational variables examined in this study, six were significant predictors in
      Madagascar (all positive), three in Mali (all positive), and two in Nigeria (both
      negative). CONCLUSION: This research suggests that the systematic use of this
      model to identify relevant ideational variables in a particular setting can guide
      the development of communication strategies and messaging, thereby improving the
      effectiveness of malaria prevention and control.

PMID- 29642884
TI  - Performance and self-perceived competencies of enrolled nurse/midwives: a mixed
      methods study from rural Tanzania.
AB  - BACKGROUND: Tanzania is experiencing a severe shortage of human resources for
      health, which poses a serious threat to the quality of health care services
      particularly in rural areas. Task shifting has been considered a way to address
      this problem. However, since a large percentage of health care providers in rural
      setting is comprised of Enrolled Nurse/Midwives (ENMs), most of the health care
      tasks are shifted to them. This article analyzes the performance and self
      perceived competencies of ENMs at the dispensary level; the lowest health
      facility in Tanzania. Performance refers to routine duties performed by ENMs, and
      self-perceived competence means self-perceived proficiency in performing
      nursing/midwifery and medical duties. METHODS: This was a mixed methods study
      conducted in rural Tanzania. A purposeful sample of twelve (12) informants (six
      ENMs; two Community Leaders [CLs] and four Dispensary In-charges [DIs]) was
      recruited for semi-structured interviews. The interviews were supplemented with
      quantitative data from 59 ENMs. Both thematic and descriptive analysis approaches
      were used. RESULTS: Three themes emerged: (1) 'Approval of the performances of
      ENMs in meeting community health needs' underscores important services the
      community members got from ENMs at dispensaries. (2) 'Experienced difficulties of
      meeting community health needs' indicate the problems ENMs encountered while
      providing services to the community. In striving to serve a large number of
      demanding clients without adequate medical equipment and supplies, sometimes the
      ENMs ended up with prescription errors (3) 'Appreciating the performances and
      competencies of ENMs' shows the acknowledgement of community members towards
      ENMs' performance and competencies within and beyond their scope of practice. The
      community members as well as ENMs and their supervisors knew that ENMs must
      sometimes provide care that is outside their scope of training and competency.
      Overall, the performance among ENMs above 38 years of age (P < 0.05) and
      participants of professional development courses (P < 0.01) was high.
      CONCLUSIONS: The results highlight performance and self-perceived competencies of
      ENMs in struggling to meet community health needs. Additionally, these results
      highlight the health care system shortfalls in supporting and developing an
      adequate number of qualified health care professionals so that health care needs
      of all citizens, including those in rural areas, are met.

PMID- 29642885
TI  - Barriers to and motivators of handwashing behavior among mothers of neonates in
      rural Bangladesh.
AB  - BACKGROUND: To design a maternal handwashing intervention for the newborn period,
      this qualitative study explored drivers of handwashing among mothers and other
      caregivers of neonates and infants in two rural areas of Bangladesh. METHODS: We
      conducted 40 semi-structured observation sessions to observe handwashing
      behaviors of primiparous and multiparous mothers of neonates, and to understand
      the contextual factors that facilitated or hampered those behaviors. We then
      conducted 64 interviews with mothers of neonates and mothers of infants and 6
      group discussions with mothers of infants, other female caregivers and fathers to
      explore perceptions, beliefs, and practices related to handwashing in the
      neonatal period. Based on a conceptual model and the Theory of Reasoned
      Action/Theory of Planned Behavior, we developed a conceptual model a priori, we
      performed thematic analysis to explain determinants of maternal handwashing
      behaviors. RESULTS: We conducted 200 h of observation among mothers of neonates.
      The age range of participating mothers varied between 17 and 25 years and their
      maximum education was up to 10th grade of schooling. Mothers, other female
      caregivers and fathers perceived a need to wash hands with or without soap before
      eating or before feeding a child by hand to prevent diarrhea. Mothers expressed
      the importance of washing their hands before holding a baby but were rarely
      observed doing so. All respondents prioritized using soap for visible dirt or
      feces; otherwise, water alone was considered sufficient. Lack of family support,
      social norms of infrequent handwashing, perceptions of frequent contact with
      water as a health threat and mothers' restricted movement during first 40 days of
      neonate's life, and childcare and household responsibilities adversely impacted
      handwashing behavior. CONCLUSIONS: Addressing emotive drivers of handwashing
      within existing social norms by engaging family members, ensuring handwashing
      facilities and clarifying neonatal health threats may improve maternal
      handwashing behavior in the neonatal period.

PMID- 29642886
TI  - A genetically and functionally diverse group of non-diazotrophic Bradyrhizobium
      spp. colonizes the root endophytic compartment of Arabidopsis thaliana.
AB  - BACKGROUND: Diazotrophic Bradyrhizobium spp. are well known for their ability to
      trigger nodule formation on a variety of legume species. In nodules,
      Bradyrhizobium utilizes plant-derived carbohydrates in exchange for fixed
      nitrogen. The genes essential for the nodulation and nitrogen-fixation trait are
      clustered in a genomic region, which is known as the 'symbiotic island'.
      Recently, novel non-diazotrophic Bradyrhizobium spp. have been found to be highly
      abundant in soils, suggesting that these species can also have a 'free-living'
      life history. However, whether non-diazotrophic Bradyrhizobium spp. can live in
      association with plants remains elusive. RESULTS: In this study, we show that
      Bradyrhizobium spp. are common root endophytes of non-legume plant species -
      including Arabidopsis thaliana (Arabidopsis) - grown in an ecological setting.
      From a single Arabidopsis root, four Bradyrhizobium sp. strains (designated
      MOS001 to MOS004) were isolated. Comparative genome analysis revealed that these
      strains were genetically and functionally highly diverse, but did not harbour the
      nodulation and the nitrogen fixation gene clusters. Comparative colonization
      experiments, with MOS strains and nitrogen-fixing symbiotic strains, revealed
      that all tested Bradyrhizobium spp. can colonize the root endophytic compartment
      of Arabidopsis. CONCLUSION: This study provides evidence that both diazotrophic
      and non-diazotrophic Bradyrhizobium spp. colonize the root endophytic compartment
      of a wide variety of plant species, including the model species Arabidopsis. This
      demonstrates that plant roots form a major ecological niche for Bradyrhizobium
      spp., which might be ancestral to the evolution of the nodulation and nitrogen
      fixation trait in this genus.

PMID- 29642887
TI  - Association between level of suicide risk, characteristics of suicide attempts,
      and mental disorders among suicide attempters.
AB  - BACKGROUND: Past attempted suicide is a strong predictor of future suicide risk,
      but the risk varies among suicide attempters. Hence, it is important to clarify
      distinguishing features of lifetime attempters with a high level of current
      suicide risk for efficient preventive management. METHODS: We compared
      characteristics of suicide attempts and clinical characteristics among high-,
      moderate-, and low-risk attempters. Among the total of 6022 participants in the
      Korean Epidemiologic Catchment Area study, 193 reported a suicide attempt in
      their lifetime, 36 of which had high, 126 moderate, and 30 low levels of current
      suicide risk (1 incomplete response). RESULTS: High-risk suicide attempters had
      more past attempts compared with moderate- and low-risk suicide attempters.
      Suicide attempts were closely linked to a wide range of psychiatric comorbidities
      regardless of degree of current level of suicide risk, but the relative risk for
      having at least one mental disorder was the highest in high-risk attempters.
      Specifically, the relative risks for depressive disorder, anxiety disorders
      including obsessive-compulsive disorder and post-traumatic stress disorder, and
      substance use disorders were higher in high-risk attempters, and relative risk
      for somatoform disorder was higher in low-risk attempters than others.
      CONCLUSIONS: Our findings indicated that special attention is required for
      suicide attempters with a history of repeated attempts and current mental
      disorders, particularly anxiety disorders.

PMID- 29642888
TI  - Reconstruction of metabolic module with improved promoter strength increases the
      productivity of 2-phenylethanol in Saccharomyces cerevisiae.
AB  - BACKGROUND: 2-phenylethanol (2-PE) is an important aromatic compound with a
      lovely rose-like scent. Saccharomyces cerevisiae is a desirable microbe for 2-PE
      production but its natural yield is not high, and one or two crucial genes' over
      expression in S. cerevisiae did not improve 2-PE greatly. RESULTS: A new
      metabolic module was established here, in which, permease Gap1p for L
      phenylalanine transportation, catalytic enzymes Aro8p, Aro10p and Adh2p in
      Ehrlich pathway respectively responsible for transamination, decarboxylation and
      reduction were assembled, besides, glutamate dehydrogenase Gdh2p was harbored for
      re-supplying another substrate 2-oxoglutarate, relieving product glutamate
      repression and regenerating cofactor NADH. Due to different promoter strengths,
      GAP1, ARO8, ARO9, ARO10, ADH2 and GDH2 in the new modularized YS58(G1-A8-A10-A2)
      GDH strain enhanced 11.6-, 15.4-, 3.6-, 17.7-, 12.4- and 7.5-folds respectively,
      and crucial enzyme activities of aromatic aminotransferases and phenylpyruvate
      decarboxylase were 4.8- and 7-folds respectively higher than that of the control.
      CONCLUSIONS: Under the optimum medium and cell density, YS58(G1-A8-A10-A2)-GDH
      presented efficient 2-PE synthesis ability with ~ 6.3 g L-1 of 2-PE titer in 5-L
      fermenter reaching 95% of conversation ratio. Under fed-batch fermentation, 2-PE
      productivity at 24 h increased 29% than that of single-batch fermentation.
      Metabolic modularization with promoter strategy provides a new prospective for
      efficient 2-PE production.

PMID- 29642889
TI  - A methodology to extract outcomes from routine healthcare data for patients with
      locally advanced non-small cell lung cancer.
AB  - BACKGROUND: Outcomes for patients in UK with locally advanced non-small cell lung
      cancer (LA NSCLC) are amongst the worst in Europe. Assessing outcomes is
      important for analysing the effectiveness of current practice. However, data
      quality is inconsistent and regular large scale analysis is challenging. This
      project investigates the use of routine healthcare datasets to determine
      progression free survival (PFS) and overall survival (OS) of patients treated
      with primary radical radiotherapy for LA NSCLC. METHODS: All LA NSCLC patients
      treated with primary radical radiotherapy in a 2 year period were identified and
      paired manual and routine data generated for an initial pilot study. Manual data
      was extracted information from hospital records and considered the gold standard.
      Key time points were date of diagnosis, recurrence, death or last clinical
      encounter. Routine data was collected from various data sources including,
      Hospital Episode Statistics, Personal Demographic Service, chemotherapy data, and
      radiotherapy datasets. Relevant event dates were defined by proxy time points and
      refined using backdating and time interval optimization. Dataset correlations
      were then tested on key clinical outcome indicators to establish if routine data
      could be used as a reliable proxy measure for manual data. RESULTS: Forty-three
      patients were identified for the pilot study. The manual data showed a median age
      of 67 years (range 46- 89 years) and all patients had stage IIIA/B disease. Using
      the manual data, the median PFS was 10.78 months (range 1.58-37.49 months) and
      median OS was 16.36 months (range 2.69-37.49 months). Based on routine data,
      using proxy measures, the estimated median PFS was 10.68 months (range 1.61-31.93
      months) and estimated median OS was 15.38 months (range 2.14-33.71 months).
      Overall, the routine data underestimated the PFS and OS of the manual data but
      there was good correlation with a Pearson correlation coefficient of 0.94 for PFS
      and 0.97 for OS. CONCLUSIONS: This is a novel approach to use routine datasets to
      determine outcome indicators in patients with LA NSCLC that will be a surrogate
      to analysing manual data. The ability to enable efficient and large scale
      analysis of current lung cancer strategies has a huge potential impact on the
      healthcare system.

PMID- 29642890
TI  - Physicians' and nurses' thoughts and concerns about introducing neonatal male
      circumcision in Thailand: a qualitative study.
AB  - BACKGROUND: Neonatal male circumcision (NMC) is an alternative approach to adult
      male circumcision for HIV prevention. Recent studies found that NMC was rarely
      performed in Thailand and that most Thai health professionals did not recognize
      that NMC could reduce the risk of HIV infection and would not want NMC services
      in their hospitals. This study explored the thoughts and concerns of Thai
      government health staff regarding the introduction of NMC in government health
      facilities as a public health measure. METHODS: In-depth interviews with
      physicians, nurses and physician administrators from four different levels of
      government hospitals in four provinces representing 4 regions of Thailand were
      conducted after provision of education regarding the benefits and risks of NMC.
      Interviews were audio recorded and analyzed using Atlas.ti software to develop
      themes. RESULTS: Six themes emerged from the data of 42 respondents:
      understanding of the benefits of NMC; risks of NMC; need for a pilot project;
      need for staff training and hospital readiness; need for parental/family
      education; and need for public awareness educational campaign. Major concerns
      included possible medical complications of NMC, infringement of child rights, and
      lack of understanding from staff and parents. The respondents emphasized the need
      for a clear policy, proper training of staff, financial and equipment support,
      and piloting NMC rollout before this measure could be fully implemented.
      CONCLUSIONS: Thai health professionals who took part in this study expressed
      several concerns if NMC had to be performed in their health care facilities.
      There is significant preparation that needs to be done before NMC can be
      introduced in the country.

PMID- 29642891
TI  - Physical activity and sedentary behavior legislation in Canadian childcare
      facilities: an update.
AB  - BACKGROUND: Within the childcare sector, physical activity and sedentary
      behaviors are not legislated at a national level in Canada. Efforts have been
      undertaken to identify factors within childcare facilities which support and
      deter physical activity and sedentary behaviors. The purpose of this paper was to
      provide an amended review of the legislative landscape, at the provincial and
      territorial level, regarding physical activity and sedentary behaviors (via
      screen-viewing) in Canadian childcare centers. METHODS: Individual childcare acts
      and regulations for each province and territory were collected; documents were
      reviewed with a focus on sections devoted to child health, physical activity,
      screen time, play, and outdoor time. An extraction table was used to facilitate
      systematic data retrieval and comparisons across provinces and territories.
      RESULTS: Of the 13 provinces and territories, 8 (62%) have updated their
      childcare regulations in the past 5 years. All provinces provide general
      recommendations to afford gross motor movement; but the majority give no specific
      requirements for how much or at what intensity. Only 3 provinces (Northwest
      Territories, Nunavut, and Nova Scotia) explicitly mentioned daily physical
      activity while all provinces' and territories' required daily outdoor play. Only
      1 province (New Brunswick) made mention of screen-viewing. CONCLUSIONS: The
      variability in childcare regulations results in different physical activity
      requirements across the country. By providing high-level targets for physical
      activity recommendations, by way of provincial/territorial legislation, staff
      would have a baseline from which to begin supporting more active behaviors among
      the children in their care. Future research is needed to support translating
      physical activity policies into improved activity levels among young children in
      childcare and the role of screen-viewing in these venues.

PMID- 29642892
TI  - A systematic and prospectively validated approach for identifying synergistic
      drug combinations against malaria.
AB  - BACKGROUND: Nearly half of the world's population (3.2 billion people) were at
      risk of malaria in 2015, and resistance to current therapies is a major concern.
      While the standard of care includes drug combinations, there is a pressing need
      to identify new combinations that can bypass current resistance mechanisms. In
      the work presented here, a combined transcriptional drug repositioning/discovery
      and machine learning approach is proposed. METHODS: The integrated approach
      utilizes gene expression data from patient-derived samples, in combination with
      large-scale anti-malarial combination screening data, to predict synergistic
      compound combinations for three Plasmodium falciparum strains (3D7, DD2 and HB3).
      Both single compounds and combinations predicted to be active were prospectively
      tested in experiment. RESULTS: One of the predicted single agents, apicidin, was
      active with the AC50 values of 74.9, 84.1 and 74.9 nM in 3D7, DD2 and HB3 P.
      falciparum strains while its maximal safe plasma concentration in human is 547.6
      +/- 136.6 nM. Apicidin at the safe dose of 500 nM kills on average 97% of the
      parasite. The synergy prediction algorithm exhibited overall precision and recall
      of 83.5 and 65.1% for mild-to-strong, 48.8 and 75.5% for moderate-to-strong and
      12.0 and 62.7% for strong synergies. Some of the prospectively predicted
      combinations, such as tacrolimus-hydroxyzine and raloxifene-thioridazine,
      exhibited significant synergy across the three P. falciparum strains included in
      the study. CONCLUSIONS: Systematic approaches can play an important role in
      accelerating discovering novel combinational therapies for malaria as it enables
      selecting novel synergistic compound pairs in a more informed and cost-effective
      manner.

PMID- 29642893
TI  - Q&A: How do gene regulatory networks control environmental responses in plants?
AB  - A gene regulatory network (GRN) describes the hierarchical relationship between
      transcription factors, associated proteins, and their target genes. Studying GRNs
      allows us to understand how a plant's genotype and environment are integrated to
      regulate downstream physiological responses. Current efforts in plants have
      focused on defining the GRNs that regulate functions such as development and
      stress response and have been performed primarily in genetically tractable model
      plant species such as Arabidopsis thaliana. Future studies will likely focus on
      how GRNs function in non-model plants and change over evolutionary time to allow
      for adaptation to extreme environments. This broader understanding will inform
      efforts to engineer GRNs to create tailored crop traits.

PMID- 29642894
TI  - Activation of melanocortin receptor 4 with RO27-3225 attenuates neuroinflammation
      through AMPK/JNK/p38 MAPK pathway after intracerebral hemorrhage in mice.
AB  - BACKGROUND: Neuroinflammation plays an important role in the pathogenesis of
      intracerebral hemorrhage (ICH)-induced secondary brain injury. Activation of
      melanocortin receptor 4 (MC4R) has been shown to elicit anti-inflammatory effects
      in many diseases. The objective of this study was to explore the role of MC4R
      activation on neuroinflammation in a mouse ICH model and to investigate the
      contribution of adenosine monophosphate-activated protein kinase (AMPK)/c-Jun N
      terminal kinase (JNK)/p38 mitogen-activated protein kinase (p38 MAPK) pathway in
      MC4R-mediated protection. METHODS: Adult male CD1 mice (n = 189) were subjected
      to intrastriatal injection of bacterial collagenase or sham surgery. The
      selective MC4R agonist RO27-3225 was administered by intraperitoneal injection at
      1 h after collagenase injection. The specific MC4R antagonist HS024 and selective
      AMPK inhibitor dorsomorphin were administered prior to RO27-3225 treatment to
      elucidate potential mechanism. Short- and long-term neurobehavioral assessments,
      brain water content, immunofluorescence staining, and western blot were
      performed. RESULTS: The expression of MC4R and p-AMPK increased after ICH with a
      peak at 24 h. MC4R was expressed by microglia, neurons, and astrocytes.
      Activation of MC4R with RO27-3225 improved the neurobehavioral functions,
      decreased brain edema, and suppressed microglia/macrophage activation and
      neutrophil infiltration after ICH. RO27-3225 administration increased the
      expression of MC4R and p-AMPK while decreasing p-JNK, p-p38 MAPK, TNF-alpha, and
      IL-1beta expression, which was reversed with inhibition of MC4R and AMPK.
      CONCLUSIONS: Our study demonstrated that activation of MC4R with RO27-3225
      attenuated neuroinflammation through AMPK-dependent inhibition of JNK and p38
      MAPK signaling pathway, thereby reducing brain edema and improving
      neurobehavioral functions after experimental ICH in mice. Therefore, the
      activation of MC4R with RO27-3225 may be a potential therapeutic approach for ICH
      management.

PMID- 29642895
TI  - Wnt3a ligand facilitates autophagy in hippocampal neurons by modulating a novel
      GSK-3beta-AMPK axis.
AB  - BACKGROUND: In the adult central nervous system (CNS), Wnt signaling regulates
      dendritic structure and synaptic plasticity. The Wnt signaling pathway can be
      divided into the canonical (beta-catenin-dependent) and non-canonical pathways.
      In the canonical pathway, the binding of canonical ligands such as Wnt3a to the
      Frizzled receptor induces inactivation of glycogen synthase kinase-3beta (GSK
      3beta), which stabilizes beta-catenin and allows its translocation to the
      nucleus. However, to date, few studies have focused on beta-catenin-independent
      Wnt signaling or explained the underlying mechanisms connecting Wnt signaling to
      cellular energy metabolism. A recent study demonstrated negative regulation of 5'
      adenosine monophosphate-activated protein kinase (AMPK), a major target of GSK
      3beta that regulates cellular metabolism under diverse conditions. Mainly based
      on these observations, we evaluated whether Wnt3a ligand modulates autophagy by
      regulating the GSK-3beta/AMPK axis. METHODS: Cultured primary hippocampal neurons
      and slices of the CA1 region of rat hippocampus were used. GSK-3beta inhibition,
      AMPK activation, PP2Ac expression, and LC3 processing were examined by western
      blotting. Autophagic compartments were studied using the CYTO-ID(r) fluorescent
      probe, and mature autophagosomes were observed via transmission electron
      microscopy (TEM). RESULTS: Wnt3a ligand, acting through the Frizzled receptor,
      promotes the rapid activation of AMPK by inactivating GSK-3beta. Biochemical
      analysis of downstream targets indicated that Wnt3a ligand modulates autophagy in
      hippocampal neurons. CONCLUSIONS: Our results revealed new aspects of Wnt
      signaling in neuronal metabolism. First, AMPK is an additional target downstream
      of the Wnt cascade, suggesting a molecular mechanism for the metabolic effects
      previously observed for Wnt signaling. Second, this mechanism is independent of
      beta-catenin, suggesting a relevant role for non-genomic activity of the Wnt
      pathway in cellular metabolism. Finally, these results have new implications
      regarding the role of Wnt signaling in the modulation of autophagy in neurons,
      with a possible role in the removal of accumulated intracellular proteins.

PMID- 29642896
TI  - L-Lactic acid production from glucose and xylose with engineered strains of
      Saccharomyces cerevisiae: aeration and carbon source influence yields and
      productivities.
AB  - BACKGROUND: Saccharomyces cerevisiae, engineered for L-lactic acid production
      from glucose and xylose, is a promising production host for lignocellulose-to
      lactic acid processes. However, the two principal engineering strategies-pyruvate
      to-lactic acid conversion with and without disruption of the competing pyruvate
      to-ethanol pathway-have not yet resulted in strains that combine high lactic acid
      yields (YLA) and productivities (QLA) on both sugar substrates. Limitations
      seemingly arise from a dependency on the carbon source and the aeration
      conditions, but the underlying effects are poorly understood. We have recently
      presented two xylose-to-lactic acid converting strains, IBB14LA1 and IBB14LA1_5,
      which have the L-lactic acid dehydrogenase from Plasmodium falciparum (pfLDH)
      integrated at the pdc1 (pyruvate decarboxylase) locus. IBB14LA1_5 additionally
      has its pdc5 gene knocked out. In this study, the influence of carbon source and
      oxygen on YLA and QLA in IBB14LA1 and IBB14LA1_5 was investigated. RESULTS: In
      anaerobic fermentation IBB14LA1 showed a higher YLA on xylose (0.27 g g Xyl-1 )
      than on glucose (0.18 g g Glc-1 ). The ethanol yields (YEtOH, 0.15 g g Xyl-1 and
      0.32 g g Glc-1 ) followed an opposite trend. In IBB14LA1_5, the effect of the
      carbon source on YLA was less pronounced (~ 0.80 g g Xyl-1 , and 0.67 g g Glc-1
      ). Supply of oxygen accelerated glucose conversions significantly in IBB14LA1
      (QLA from 0.38 to 0.81 g L-1 h-1) and IBB14LA1_5 (QLA from 0.05 to 1.77 g L-1 h
      1) at constant YLA (IBB14LA1 ~ 0.18 g g Glc-1 ; IBB14LA1_5 ~ 0.68 g g Glc-1 ). In
      aerobic xylose conversions, however, lactic acid production ceased completely in
      IBB14LA1 and decreased drastically in IBB14LA1_5 (YLA aerobic <= 0.25 g g Xyl-1
      and anaerobic ~ 0.80 g g Xyl-1 ) at similar QLA (~ 0.04 g L-1 h-1). Switching
      from aerobic to microaerophilic conditions (pO2 ~ 2%) prevented lactic acid
      metabolization, observed for fully aerobic conditions, and increased QLA and YLA
      up to 0.11 g L-1 h-1 and 0.38 g g Xyl-1 , respectively. The pfLDH and PDC
      activities in IBB14LA1 were measured and shown to change drastically dependent on
      carbon source and oxygen. CONCLUSION: Evidence from conversion time courses
      together with results of activity measurements for pfLDH and PDC show that in
      IBB14LA1 the distribution of fluxes at the pyruvate branching point is carbon
      source and oxygen dependent. Comparison of the performance of strain IBB14LA1 and
      IBB14LA1_5 in conversions under different aeration conditions (aerobic,
      anaerobic, and microaerophilic) further suggest that xylose, unlike glucose, does
      not repress the respiratory response in both strains. This study proposes new
      genetic engineering targets for rendering genetically engineering S. cerevisiae
      better suited for lactic acid biorefineries.

PMID- 29642897
TI  - Small contribution of gold mines to the ongoing tuberculosis epidemic in South
      Africa: a modeling-based study.
AB  - BACKGROUND: Gold mines represent a potential hotspot for Mycobacterium
      tuberculosis (Mtb) transmission and may be exacerbating the tuberculosis (TB)
      epidemic in South Africa. However, the presence of multiple factors complicates
      estimation of the mining contribution to the TB burden in South Africa. METHODS:
      We developed two models of TB in South Africa, a static risk model and an
      individual-based model that accounts for longer-term trends. Both models account
      for four populations - mine workers, peri-mining residents, labor-sending
      residents, and other residents of South Africa - including the size and
      prevalence of latent TB infection, active TB, and HIV of each population and
      mixing between populations. We calibrated to mine- and country-level data and
      used the static model to estimate force of infection (FOI) and new infections
      attributable to local residents in each community compared to other residents.
      Using the individual-based model, we simulated a counterfactual scenario to
      estimate the fraction of overall TB incidence in South Africa attributable to
      recent transmission in mines. RESULTS: We estimated that the majority of FOI in
      each community is attributable to local residents: 93.9% (95% confidence interval
      92.4-95.1%), 91.5% (91.4-91.5%), and 94.7% (94.7-94.7%) in gold mining, peri
      mining, and labor-sending communities, respectively. Assuming a higher rate of
      Mtb transmission in mines, 4.1% (2.6-5.8%), 5.0% (4.5-5.5%), and 9.0% (8.8-9.1%)
      of new infections in South Africa are attributable to gold mine workers, peri
      mining residents, and labor-sending residents, respectively. Therefore, mine
      workers with TB disease, who constitute ~ 2.5% of the prevalent TB cases in South
      Africa, contribute 1.62 (1.04-2.30) times as many new infections as TB cases in
      South Africa on average. By modeling TB on a longer time scale, we estimate 63.0%
      (58.5-67.7%) of incident TB disease in gold mining communities to be attributable
      to recent transmission, of which 92.5% (92.1-92.9%) is attributable to local
      transmission. CONCLUSIONS: Gold mine workers are estimated to contribute a
      disproportionately large number of Mtb infections in South Africa on a per-capita
      basis. However, mine workers contribute only a small fraction of overall Mtb
      infections in South Africa. Our results suggest that curtailing transmission in
      mines may have limited impact at the country level, despite potentially
      significant impact at the mining level.

PMID- 29642898
TI  - Enablers and barriers for women with gestational diabetes mellitus to achieve
      optimal glycaemic control - a qualitative study using the theoretical domains
      framework.
AB  - BACKGROUND: Glycaemic target recommendations vary widely between international
      professional organisations for women with gestational diabetes mellitus (GDM).
      Some studies have reported women's experiences of having GDM, but little is known
      how this relates to their glycaemic targets. The aim of this study was to
      identify enablers and barriers for women with GDM to achieve optimal glycaemic
      control. METHODS: Women with GDM were recruited from two large, geographically
      different, hospitals in New Zealand to participate in a semi-structured interview
      to explore their views and experiences focusing on enablers and barriers to
      achieving optimal glycaemic control. Final thematic analysis was performed using
      the Theoretical Domains Framework. RESULTS: Sixty women participated in the
      study. Women reported a shift from their initial negative response to accepting
      their diagnosis but disliked the constant focus on numbers. Enablers and barriers
      were categorised into ten domains across the three study questions. Enablers
      included: the ability to attend group teaching sessions with family and hear from
      women who have had GDM; easy access to a diabetes dietitian with diet
      recommendations tailored to a woman's context including ethnic food and financial
      considerations; free capillary blood glucose (CBG) monitoring equipment, health
      shuttles to take women to appointments; child care when attending clinic
      appointments; and being taught CBG testing by a community pharmacist. Barriers
      included: lack of health information, teaching sessions, consultations, and food
      diaries in a woman's first language; long waiting times at clinic appointments;
      seeing a different health professional every clinic visit; inconsistent advice;
      no tailored physical activities assessments; not knowing where to access
      appropriate information on the internet; unsupportive partners, families, and
      workplaces; and unavailability of social media or support groups for women with
      GDM. Perceived judgement by others led some women only to share their GDM
      diagnosis with their partners. This created social isolation. CONCLUSION: Women
      with GDM report multiple enablers and barriers to achieving optimal glycaemic
      control. The findings of this study may assist health professionals and diabetes
      in pregnancy services to improve their care for women with GDM and support them
      to achieve optimal glycaemic control.

PMID- 29642899
TI  - Determinants of malaria infection in Dembia district, Northwest Ethiopia: a case
      control study.
AB  - BACKGROUND: Despite the progress in reducing malaria infections and related
      deaths, the disease remains a major global public health problem. The problem is
      among the top five leading causes of outpatient visits in Dembia district of the
      northwest Ethiopia. Therefore, this study aimed to assess the determinants of
      malaria infections in the district. METHODS: An institution-based case-control
      study was conducted in Dembia district from October to November 2016. Out of the
      ten health centers in the district, four were randomly selected for the study in
      which 370 participants (185 cases and 185 controls) were enrolled. Data were
      collected using a pretested structured questionnaire. Factors associated with
      malaria infections were determined using logistic regression analysis. Odds ratio
      with 95% CI was used as a measure of association, and variables with a p-value of
      <=0.05 were considered as statistically significant. RESULTS: The median age of
      all participants was 26 years, while that of cases and controls was 22 and 30
      with a range of 1 to 80 and 2 to 71, respectively. In the multivariable logistic
      regression, over 15 years of age adjusted odds ratio(AOR) and confidence interval
      (CI) of (AOR = 18; 95% CI: 2.1, 161.5), being male (AOR = 2.2; 95% CI: 1.2, 3.9),
      outdoor activities at night (AOR = 5.7; 95% CI: 2.5, 12.7), bed net sharing (AOR
      = 3.9; 95% CI: 2.0, 7.7), and proximity to stagnant water sources (AOR = 2.7; 95%
      CI: 1.3, 5.4) were independent predictors. CONCLUSION: Being in over 15 years of
      age group, male gender, night time activity, bed net sharing and proximity to
      stagnant water sources were determinant factors of malaria infection in Dembia
      district. Additional interventions and strategies which focus on men, outdoor
      work at night, household net utilization, and nearby stagnant water sources are
      essential to reduce malaria infections in the area.

PMID- 29642900
TI  - Cisplatin based therapy: the role of the mitogen activated protein kinase
      signaling pathway.
AB  - Cisplatin is a widely used chemotherapeutic agent for treatment of various
      cancers. However, treatment with cisplatin is associated with drug resistance and
      several adverse side effects such as nephrotoxicity, reduced immunity towards
      infections and hearing loss. A Combination of cisplatin with other drugs is an
      approach to overcome drug resistance and reduce toxicity. The combination therapy
      also results in increased sensitivity of cisplatin towards cancer cells. The
      mitogen activated protein kinase (MAPK) pathway in the cell, consisting of
      extracellular signal regulated kinase, c-Jun N-terminal kinase, p38 kinases, and
      downstream mediator p90 ribosomal s6 kinase (RSK); is responsible for the
      regulation of various cellular events including cell survival, cell
      proliferation, cell cycle progression, cell migration and protein translation.
      This review article demonstrates the role of MAPK pathway in cisplatin based
      therapy, illustrates different combination therapy involving cisplatin and also
      shows the importance of targeting MAPK family, particularly RSK, to achieve
      increased anticancer effect and overcome drug resistance when combined with
      cisplatin.

PMID- 29642901
TI  - Profile of osteopathic practice in Spain: results from a standardized data
      collection study.
AB  - BACKGROUND: There is limited research regarding patients' profiles and consumer
      attitudes and habits of osteopathy in Spain. The purpose of this study was to
      profile patients who regularly receive osteopathic care in Spain using an
      internationally developed standardized data collection tool. METHOD: During the
      period between April 2014 and December 2015, a UK-developed standardized data
      collection tool was distributed to Spanish osteopaths who voluntarily agreed to
      participate in this cross-sectional study. RESULTS: Thirty-six osteopaths
      participated in this study and returned a total of 314 completed datasets. Of 314
      patients, 61% were women and 39% were men, with a mean age of 40 years (SD 17.02
      years, range 0 to 83 years). Forty-four percent were full-time salaried workers,
      and in 78% of cases, receiving osteopathic treatment was the patient's own
      choice. Chronic spinal pain presentations were the most frequent reasons for
      consultation. Seventy-five percent of patients presented with a coexisting
      condition, mainly gastrointestinal disorders and headaches. The main treatment
      approach consisted of mobilization techniques, followed by soft tissue, cranial
      and high velocity thrust techniques. Improvement or resolution of the complaint
      was experienced by 93% of patients after a small number of sessions. Adverse
      events were minor and occurred in 7% of all cases. CONCLUSION: This is the first
      study carried out in Spain analyzing the profile of patients who receive
      osteopathic care. The typical patient who receives osteopathic care in Spain is
      middle-aged, presents mainly with chronic spinal pain, and voluntarily seeks
      osteopathic treatment. Osteopathic treatment produces a significant improvement
      in the majority of cases with a low rate of minor adverse events reported.

PMID- 29642902
TI  - The public health emergency management system in China: trends from 2002 to 2012.
AB  - BACKGROUND: Public health emergencies have challenged the public health emergency
      management systems (PHEMSs) of many countries critically and frequently since
      this century. As the world's most populated country and the second biggest
      economy in the world, China used to have a fragile PHEMS; however, the government
      took forceful actions to build PHEMS after the 2003 SARS outbreak. After more
      than one decade's efforts, we tried to assess the improvements and problems of
      China's PHEMS between 2002 and 2012. METHODS: We conducted two rounds of national
      surveys and collected the data of the year 2002 and 2012, including all 32
      provincial, 139 municipal, and 489 county CDCs. The municipal and county CDCs
      were selected by systematic random sampling. Twenty-one indicators of four stages
      (preparation, readiness, response and recovery) from the National Assessment
      Criteria for CDC Performance were chosen to assess the ten-year trends. RESULTS:
      At the preparation stage, organization, mechanisms, workforce, and stockpile
      across all levels and regions were significantly improved after one decade's
      efforts. At the readiness stage, the capability for formulating an emergency plan
      was also significantly improved during the same period. At the response stage,
      internet-based direct reporting was 98.8%, and coping scores were nearly full
      points of ten in 2012. At the recovery stage, the capabilities were generally
      lower than expected. CONCLUSIONS: Due to forceful leadership, sounder
      regulations, and intensive resources, China's PHEMS has been improved at the
      preparation, readiness, and response stages; however, the recovery stage was
      still weak and could not meet the requirements of crisis management and
      preventive governance. In addition, CDCs in the Western region and counties
      lagged behind in performance on most indicators. Future priorities should include
      developing the recovery stage, establishing a closed feedback loop, and
      strengthening the capabilities of CDCs in Western region and counties.

PMID- 29642904
TI  - Relationships between aeroallergen levels and hospital admissions for asthma in
      the Brussels-Capital Region: a daily time series analysis.
AB  - BACKGROUND: Outdoor pollen grain and fungal spore concentrations have been
      associated with severe asthma exacerbations at the population level. The specific
      impact of each taxon and the concomitant effect of air pollution on these
      symptoms have, however, still to be better characterized. This study aimed to
      investigate the short-term associations between ambient concentrations of various
      aeroallergens and hospitalizations related to asthma in the Brussels-Capital
      Region (Belgium), an area recording especially high rates of admissions. METHODS:
      Based on administrative records of asthma hospitalizations and regular monitoring
      of 11 tree/herbaceous pollen taxa and 2 fungal spore taxa, daily time series
      analyses covering the 2008-2013 period were performed. Effects up to 6 days after
      exposure were captured by combining quasi-Poisson regression with distributed lag
      models, adjusting for seasonal and long-term trends, day of the week, public
      holidays, mean temperature and relative humidity. Effect modification by age and
      air pollution (PM, NO2, O3) was tested. RESULTS: A significant increase in asthma
      hospitalizations was observed for an interquartile range increase in grass (5.9%,
      95% CI: 0.0, 12.0), birch (3.2%, 95% CI: 1.1, 5.3) and hornbeam (0.7%, 95% CI:
      0.2, 1.3) pollen concentrations. For several taxa including grasses, an age
      modification effect was notable, the hospitalization risk tending to be higher in
      individuals younger than 60 years. Air pollutants impacted the relationships too:
      the risk appeared to be stronger for grass and birch pollen concentrations in
      case of high PM10 and O3 concentrations respectively. CONCLUSIONS: These findings
      suggest that airborne grass, birch and hornbeam pollen are associated with severe
      asthma exacerbations in the Brussels region. These compounds appear to act in
      synergy with air pollution and to more specifically affect young and intermediate
      age groups. Most of these life-threatening events could theoretically be
      prevented with improved disease diagnosis/management and targeted communication
      actions.

PMID- 29642903
TI  - Functional domains of SP110 that modulate its transcriptional regulatory function
      and cellular translocation.
AB  - BACKGROUND: SP110, an interferon-induced nuclear protein, belongs to the
      SP100/SP140 protein family. Very recently, we showed that SP110b, an SP110
      isoform, controls host innate immunity to Mycobacterium tuberculosis infection by
      regulating nuclear factor-kappaB (NF-kappaB) activity. However, it remains
      unclear how the structure of SP110 relates to its cellular functions. In this
      study, we provide experimental data illustrating the protein domains that are
      responsible for its functions. METHODS: We examined the effects of SP110 isoforms
      and a series of deletion mutants of SP110 on transcriptional regulation by
      luciferase reporter assays. We also employed confocal microscopy to determine the
      cellular distributions of enhanced green fluorescent protein-tagged SP110
      isoforms and SP110 mutants. In addition, we performed immunoprecipitation and
      Western blotting analyses to identify the regions of SP110 that are responsible
      for protein interactions. RESULTS: Using reporter assays, we first demonstrated
      that SP110 isoforms have different regulatory effects on NF-kappaB-mediated
      transcription, supporting the notion that SP110 isoforms may have distinct
      cellular functions. Analysis of deletion mutants of SP110 showed that the
      interaction of the N-terminal fragment (amino acids 1-276) of SP110 with p50, a
      subunit of NF-kappaB, in the cytoplasm plays a crucial role in the down
      regulation of the p50-driven tumor necrosis factor-alpha (TNFalpha) promoter
      activity in the nucleus, while the middle and C-terminal regions of SP110
      localize it to various cellular compartments. Surprisingly, a nucleolar
      localization signal (NoLS) that contains one monopartite nuclear localization
      signal (NLS) and one bipartite NLS was identified in the middle region of SP110.
      The identification of a cryptic NoLS in the SP110 suggests that although this
      protein forms nuclear speckles in the nucleoplasm, it may be directed into the
      nucleolus to carry out distinct functions under certain cellular conditions.
      CONCLUSIONS: The findings from this study elucidating the multidomain structure
      of the SP110 not only identify functional domains of SP110 that are required for
      transcriptional regulation, cellular translocation, and protein interactions but
      also implicate that SP110 has additional functions through its unexpected
      activity in the nucleolus.

PMID- 29642905
TI  - High use of private providers for first healthcare seeking by drug-resistant
      tuberculosis patients: a cross-sectional study in Yangon, Myanmar.
AB  - BACKGROUND: Drug resistance is a growing challenge to tuberculosis (TB) control
      worldwide, but particularly salient to countries such as Myanmar, where the
      health system is fragmented across the public and private sector. A recent
      systematic review has identified a critical lack of evidence for local
      policymaking, particularly in relation to drivers of drug-resistance that could
      be the target of preventative efforts. To address this gap from a health systems
      perspective, our study investigates the healthcare-seeking behavior and
      preferences of recently diagnosed patients with drug-resistant tuberculosis (DR
      TB), focusing on the use of private versus public healthcare providers. METHODS:
      The study was conducted in ten townships across Yangon with high DR-TB burden.
      Patients newly-diagnosed with DR-TB by GeneXpert were enrolled, and data on
      healthcare-seeking behavior and socio-economic characteristics were collected
      from patient records and interviews. A descriptive analysis of healthcare-seeking
      behavior was followed by the investigation of relationships between socio
      economic factors and type of provider visited upon first feeling unwell, through
      univariate logistic regressions. RESULTS: Of 202 participants, only 8% reported
      first seeking care at public facilities, while 88% reported seeking care at
      private facilities upon first feeling unwell. Participants aged 25-34 (Odds Ratio
      = 0.33 [0.12-0.95]) and males (Odds Ratio = 0.39 [0.20-0.75]) were less likely to
      visit a private clinic or hospital than those aged 18-24 and females,
      respectively. In contrast, participants with higher income were more likely to
      utilize private providers. Prior to DR-TB diagnosis, 86% of participants took
      medications from private providers. After DR-TB diagnosis, only 7% of
      participants continued to take medications from private providers. CONCLUSION: In
      urban Myanmar, most patients shifted to being managed exclusively in the public
      sector after being formally diagnosed with DR-TB. However, since the vast
      majority of DR-TB patients first visited private providers in the period leading
      to diagnosis, related issues such as unregulated quality of care, potential
      delays to diagnosis, and lack of care continuity may greatly influence the
      emergence of drug-resistance. A greater understanding of the health system and
      these healthcare-seeking behaviors may simultaneously strengthen TB control
      programmes and reduce government and out-of-pocket expenditures on the management
      of DR-TB.

PMID- 29642906
TI  - Ethical learning on international medical electives: a case-based analysis of
      medical student learning experiences.
AB  - BACKGROUND: Students on international medical electives face complex ethical
      issues when undertaking clinical work. The variety of elective destinations and
      the culturally specific nature of clinical ethical issues suggest that pre
      elective preparation could be supplemented by in-elective support. METHODS: An
      online, asynchronous, case-based discussion was piloted to support ethical
      learning on medical student electives. We developed six scenarios from elective
      diaries to stimulate peer-facilitated discussions during electives. We evaluated
      the transcripts to assess whether transformative, experiential learning took
      place, assessing specifically for indications that 1) critical reflection, 2)
      reflective action and 3) reflective learning were taking place. We also completed
      a qualitative thematic content analysis of the discussions. RESULTS: Of forty-one
      extended comments, nine responses showed evidence of transformative learning
      (Mezirow stage three). The thematic analysis identified five themes: adopting a
      position on ethical issues without overt analysis; presenting issues in terms of
      their effects on students' ability to complete tasks; describing local contexts
      and colleagues as "other"; difficulty navigating between individual and
      structural issues, and overestimation of the impact of individual action on
      structures and processes. CONCLUSION: Results suggest a need to: frame ethical
      learning on elective so that it builds on earlier ethical programmes in the
      curriculum, and encourages students to adopt structured approaches to complex
      ethical issues including cross-cultural negotiation and to enhance global health
      training within the curriculum.

PMID- 29642907
TI  - Equity of access to maternal health interventions in Brazil and Colombia: a
      retrospective study.
AB  - BACKGROUND: Reducing maternal mortality is a top priority in Latin American
      countries. Despite the progress in maternal mortality reduction, Brazil and
      Colombia still lag behind countries at similar levels of development. METHODS:
      Using data from the Demographic Health Survey, this study quantified and
      compared, by means of concentration indices, the socioeconomic-related inequity
      in access to four key maternal health interventions in Brazil and Colombia.
      Decomposition analysis of the concentration index was used for two indicators -
      skilled attendance at birth and postnatal care in Brazil. RESULTS: Coverage
      levels of the four key maternal health interventions were similar in the two
      countries. More specifically, we found that coverage of some of the interventions
      (e.g. ante-natal care and skilled birth assistance) was higher than 90% in both
      countries. Nevertheless, the concentration index analysis pointed to significant
      pro-rich inequities in access in all four key interventions in both countries.
      Interestingly, the analysis showed that Colombia fared slightly better than
      Brazil in terms of equity in access of the interventions studied. Finally, the
      decomposition analysis for the presence of a skilled attendant at birth and
      postnatal care in Brazil underlined the significance of regional disparities,
      wealth inequalities, inequalities in access to private hospitals, and
      inequalities in access to private health insurance. CONCLUSIONS: There are
      persistent pro-rich inequities in access to four maternal health interventions in
      both Brazil and Colombia. The decomposition analysis conducted on Brazilian data
      suggests the existence of disparities in system capacity and quality of care
      between the private and the public health services, resulting in inequities of
      access to maternal health services.

PMID- 29642908
TI  - Putative human sperm Interactome: a networks study.
AB  - BACKGROUND: For over sixty years, it has been known that mammalian spermatozoa
      immediately after ejaculation are virtually infertile. They became able to
      fertilize only after they reside for long time (hours to days) within female
      genital tract where they complete their functional maturation, the capacitation.
      This process is finely regulated by the interaction with the female environment
      and involves, in spermatozoa, a myriad of molecules as messengers and target of
      signals. Since, to date, a model able to represent the molecular interaction that
      characterize sperm physiology does not exist, we realized the Human Sperm
      Interactme Network3.0 (HSIN3.0) and its main component (HSNI3.0_MC), starting
      from the pathway active in male germ cells. RESULTS: HSIN3.0 and HSIN3.0_MC are
      scale free networks, adherent to the Barabasi-Albert model, and are characterised
      by an ultra-small world topology. We found that they are resistant to random
      attacks and that are designed to respond quickly and specifically to external
      inputs. In addition, it has been possible to identify the most connected nodes
      (the hubs) and the bottlenecks nodes. This result allowed us to explore the
      control mechanisms active in driving sperm biochemical machinery and to verify
      the different levels of controls: party vs. date hubs and hubs vs. bottlenecks,
      thanks the availability of data from KO mice. Finally, we found that several key
      nodes represent molecules specifically involved in function that are thought to
      be not present or not active in sperm cells, such as control of cell cycle,
      proteins synthesis, nuclear trafficking, and immune response, thus potentially
      open new perspectives on the study of sperm biology. CONCLUSIONS: For the first
      time we present a network representing putative human sperm interactome. This
      result gives very intriguing biological information and could contribute to the
      knowledge of spermatozoa, either in physiological or pathological conditions.

PMID- 29642909
TI  - Clinical implementation of rapid CYP2C19 genotyping to guide antiplatelet therapy
      after percutaneous coronary intervention.
AB  - BACKGROUND: The CYP2C19 nonfunctional genotype reduces clopidogrel effectiveness
      after percutaneous coronary intervention (PCI). Following clinical implementation
      of CYP2C19 genotyping at University Florida (UF) Health Shands Hospital in 2012,
      where genotype results are available approximately 3 days after PCI, testing was
      expanded to UF Health Jacksonville in 2016 utilizing a rapid genotyping approach.
      We describe metrics with this latter implementation. METHODS: Patients at UF
      Health Jacksonville undergoing left heart catheterization with intent to undergo
      PCI were targeted for genotyping using the Spartan RXTM system. Testing metrics
      and provider acceptance of testing and response to genotype results were
      examined, as was antiplatelet therapy over the 6 months following genotyping.
      RESULTS: In the first year, 931 patients, including 392/505 (78%) total patients
      undergoing PCI, were genotyped. The median genotype test turnaround time was 96
      min. Genotype results were available for 388 (99%) PCI patients prior to
      discharge. Of 336 genotyped PCI patients alive at discharge and not enrolled in
      an antiplatelet therapy trial, 1/6 (17%) poor metabolizers (PMs, with two
      nonfunctional alleles), 38/93 (41%) intermediate metabolizers (IMs, with one
      nonfunctional allele), and 119/237 (50%) patients without a nonfunctional allele
      were prescribed clopidogrel (p = 0.110). Clopidogrel use was higher among non-ACS
      versus ACS patients (78.6% vs. 42.2%, p < 0.001). Six months later, among
      patients with follow-up data, clopidogrel was prescribed in 0/4 (0%) PMs, 33/65
      (51%) IMs, and 115/182 (63%) patients without a nonfunctional allele (p = 0.008
      across groups; p = 0.020 for PMs versus those without a nonfunctional allele).
      CONCLUSION: These data demonstrate that rapid genotyping is clinically feasible
      at a high volume cardiac catheterization facility and allows informed chronic
      antiplatelet prescribing, with lower clopidogrel use in PMs at 6 months. Trial
      registration ClinicalTrials.gov Identifier: NCT02724319; registered March 31,
      2016; https://www.clinicaltrials.gov/ct2/show/NCT02724319?term=angiolillo&rank=7.

PMID- 29642910
TI  - Localization and phosphorylation of Plasmodium falciparum nicotinamide/nicotinate
      mononucleotide adenylyltransferase (PfNMNAT) in intraerythrocytic stages.
AB  - BACKGROUND: Nicotinamide adenine dinucleotide (NAD+) is an essential molecule in
      the energy metabolism of living beings, and it has various cellular functions.
      The main enzyme in the biosynthesis of this nucleotide is nicotinamide/nicotinate
      mononucleotide adenylyltransferase (NMNAT, EC 2.7.7.1/18) because it is the
      convergence point for all known biosynthetic pathways. NMNATs have divergences in
      both the number of isoforms detected and their distribution, depending on the
      organism. METHODS: In the laboratory of basic research in biochemistry (LIBBIQ:
      acronym in Spanish) the NMNATs of protozoan parasites (Leishmania braziliensis,
      Plasmodium falciparum, Trypanosoma cruzi, and Giardia duodenalis) have been
      studied, analysing their catalytic properties through the use of proteins.
      Recombinants and their cellular distribution essentially. In 2014, O'Hara et al.
      determined the cytoplasmic localization of NMNAT of P. falciparum, using a
      transgene coupled to GFP, however, the addition of labels to the study protein
      can modify several of its characteristics, including its sub-cellular
      localization. RESULTS: This study confirms the cytoplasmic localization of this
      protein in the parasite through recognition of the endogenous protein in the
      different stages of the asexual life cycle. Additionally, the study found that
      PfNMNAT could be a phosphorylation target at serine, tyrosine and threonine
      residues, and it shows variations during the asexual life cycle. CONCLUSIONS:
      These experiments confirmed that the parasite is situated in the cytoplasm,
      fulfilling the required functions of NAD+ in this compartment, the PfNMNAT is
      regulated in post-transcription processes, and can be regulated by
      phosphorylation in its residues.

PMID- 29642911
TI  - GnRH dysregulation in polycystic ovarian syndrome (PCOS) is a manifestation of an
      altered neurotransmitter profile.
AB  - BACKGROUND: GnRH is the master molecule of reproduction that is influenced by
      several intrinsic and extrinsic factors such as neurotransmitters and
      neuropeptides. Any alteration in these regulatory loops may result in
      reproductive-endocrine dysfunction such as the polycystic ovarian syndrome
      (PCOS). Although low dopaminergic tone has been associated with PCOS, the role of
      neurotransmitters in PCOS remains unknown. The present study was therefore aimed
      at understanding the status of GnRH regulatory neurotransmitters to decipher the
      neuroendocrine pathology in PCOS. METHODS: PCOS was induced in rats by oral
      administration of letrozole (aromatase inhibitor). Following PCOS validation,
      animals were assessed for gonadotropin levels and their mRNA expression.
      Neurotrasnmitter status was evaluated by estimating their levels, their
      metabolism and their receptor expression in hypothalamus, pituitary, hippocampus
      and frontal cortex of PCOS rat model. RESULTS: We demonstrate that GnRH and LH
      inhibitory neurotransmitters - serotonin, dopamine, GABA and acetylcholine - are
      reduced while glutamate, a major stimulator of GnRH and LH release, is increased
      in the PCOS condition. Concomitant changes were observed for neurotransmitter
      metabolising enzymes and their receptors as well. CONCLUSION: Our results reveal
      that increased GnRH and LH pulsatility in PCOS condition likely result from the
      cumulative effect of altered GnRH stimulatory and inhibitory neurotransmitters in
      hypothalamic-pituitary centre. This, we hypothesise, is responsible for the
      depression and anxiety-like mood disorders commonly seen in PCOS women.

PMID- 29642912
TI  - Preoperative metabolic tumor volume of intrahepatic cholangiocarcinoma measured
      by 18F-FDG-PET is associated with the KRAS mutation status and prognosis.
AB  - BACKGROUND: Surgical resection remains the mainstay of curative treatment for
      intrahepatic cholangiocarcinoma (ICC). Prognosis after surgery is unsatisfactory
      despite improvements in treatment and post-operative clinical management. Despite
      developments in the molecular profiling of ICC, the preoperative prediction of
      prognosis remains a challenge. This study aimed to identify clinical prognostic
      indicators by investigating the molecular profiles of ICC and evaluating the
      preoperative imaging data of 18F-fluorodeoxyglucose positron emission tomography
      (18F-FDG-PET). METHODS: A retrospective analysis was performed on 50 consecutive
      patients with ICC who underwent curative hepatectomy after 18F-FDG-PET
      examination. To evaluate the molecular profiles of ICC, KRAS mutation status was
      assessed in resected specimens. For the assessment of glucose uptake, we observed
      the expression of glucose transporter-1 (GLUT-1) by immunohistochemistry. The
      data of 18F-FDG-PET were re-evaluated as follows: maximum standardized uptake
      value, metabolic tumor volume (MTV), and total lesion glycolysis (TLG). Cut-off
      values were determined using receiver operating characteristic (ROC) curve
      analysis. Cumulative overall survival (OS) was analyzed using the Kaplan-Meier
      analysis. RESULTS: Overall, 16 (32.0%) patients had mutations in KRAS. Patients
      with mutated KRAS exhibited shorter OS than those with wild-type KRAS (5-year OS,
      0% vs. 35.1%, P < 0.001). GLUT-1 expression was significantly higher in tumors
      with mutated KRAS than in tumors with wild-type KRAS (median, 4.0 vs. 1.0, P <
      0.001). Survival was significantly different when stratified by expression of
      GLUT-1 (5-year OS, 0% vs. 46.5%, P <0.001). Among the 18F-FDG-PET parameters, the
      MTV and TLG were significantly higher in the mutated KRAS group than in the wild
      type KRAS group (P = 0.013 and P = 0.026, respectively). ROC curve analysis
      revealed a cut-off value of 38 for the MTV, with the highest accuracy (area under
      the curve = 0.789; 95% confidence interval, 0.581-0.902) for predicting KRAS
      mutation. This cut-off value permitted stratification of OS (high vs. low: 5-year
      OS, 13.1% vs. 36.7%, P = 0.008). CONCLUSIONS: High MTV is associated with KRAS
      mutation and poor postoperative outcomes in patients with ICC, suggesting that
      the MTV of ICC measured by 18F-FDG-PET may provide useful information for tumor
      molecular profiles and prognosis.

PMID- 29642913
TI  - A narrative synthesis of research evidence for tinnitus-related complaints as
      reported by patients and their significant others.
AB  - BACKGROUND: There are a large number of assessment tools for tinnitus, with
      little consensus on what it is important to measure and no preference for a
      minimum reporting standard. The item content of tinnitus assessment tools should
      seek to capture relevant impacts of tinnitus on everyday life, but no-one has yet
      synthesised information about the range of tinnitus complaints. This review is
      thus the first comprehensive and authoritative collection and synthesis of what
      adults with tinnitus and their significant others report as problems in their
      everyday lives caused by tinnitus. METHODS: Electronic searches were conducted in
      PubMed, Embase, CINAHL, as well as grey literature sources to identify
      publications from January 1980 to June 2015 in which participants were enrolled
      because tinnitus was their primary complaint. A manual search of seven relevant
      journals updated the search to December 2017. Of the 3699 titles identified
      overall, 84 records (reporting 86 studies) met our inclusion criteria and were
      taken through to data collection. Coders collated generic and tinnitus-specific
      complaints reported by people with tinnitus. All relevant data items were then
      analyzed using an iterative approach to narrative synthesis to form domain
      groupings representing complaints of tinnitus, which were compared patients and
      significant others. RESULTS: From the 86 studies analyzed using data collected
      from 16,381 patients, 42 discrete complaints were identified spanning physical
      and psychological health, quality of life and negative attributes of the tinnitus
      sound. This diversity was not captured by any individual study alone. There was
      good convergence between complaints collected using open- and closed-format
      questions, with the exception of general moods and perceptual attributes of
      tinnitus (location, loudness, pitch and unpleasantness); reported only using
      closed questions. Just two studies addressed data from the perspective of
      significant others (n = 79), but there was substantial correspondence with the
      patient framework, especially regarding relationships and social life.
      CONCLUSIONS: Our findings contribute fundamental new knowledge and a unique
      resource that enables investigators to appreciate the broad impacts of tinnitus
      on an individual. Our findings can also be used to guide questions during
      diagnostic assessment, to evaluate existing tinnitus-specific HR-QoL
      questionnaires and develop new ones, where necessary. TRIAL REGISTRATION:
      PROSPERO registration number: CRD42015020629 . Protocol published in BMJ Open.
      2016;6e009171.

PMID- 29642914
TI  - Development of the Italian version of the High-Activity Arthroplasty Score (HAAS
      I) following hip and knee total arthroplasty: cross-cultural adaptation,
      reliability, validity and sensitivity to change.
AB  - BACKGROUND: The number of physically active individuals who develop knee and hip
      arthritis and who undergo arthroplasties of these joints ie ever increasing. It
      has become necessary to develop evaluation scales which address the specific
      issues raised by such individuals. The High Activity Arthroplasty Score is one
      such scales, originally developed in English. METHODS: The HAAS-I was developed
      by means of forward-backward translation, a final review by an expert committee
      and a test of the pre-final version to establish its correspondence with the
      original English version. The psychometric testing included reliability by means
      of internal consistency (Cronbach's alpha) and test-retest reliability
      (intraclass correlation coefficients) and construct validity by Pearson's
      correlations with a pain intensity numerical rating scale (NRS), the Western
      Ontario and McMaster University index (WOMAC, for THA subjects), the Knee injury
      and Osteoarthritis Outcome Scale (KOOS; for TKA subjects) and the Short-Form 36
      Health Survey (SF-36). RESULTS: The questionnaire was administered to 67 subjects
      with THA and 61 with TKA and proved to be acceptable. The questionnaire showed
      good internal consistency (0.85 for THA and 0.91 for TKA) and a high level of
      test-retest reliability (ICC = 0.97 with 95% CI 0.95-0.98 for THA; ICC = 0.95
      with 95% CI 0.92-0.98 for TKA). There was a moderate correlation between the HAAS
      I and NRS (r = - 0.40), there was a high correlation between the HAAS-I and WOMAC
      (r = - 0.68) and there were moderate to high correlations between the HAAS-I and
      SF-36 subscales (r = 0.34 to 0.63) for THA. There was a moderate correlation
      between the HAAS-I and NRS (r = - 0.77); there was a high correlation between the
      HAAS-I and KOOS subscales (r = - 0.79 to r = - 0.91); and there were low
      correlations between the HAAS-I and SF-36 subscales (r = 0.01 to 0.29) for TKA.
      CONCLUSIONS: The HAAS-I was successfully translated into Italian and proved to
      have good psychometric properties that replicated the results of existing
      versions. Its use is recommended for clinical and research purposes.

PMID- 29642915
TI  - Adipokine RBP4 drives ovarian cancer cell migration.
AB  - BACKGROUND: Obesity has been linked to several types of cancers including ovarian
      cancer. Retinol binding protein 4 (RBP4) is an adipokine that drives the
      development of hyperinsulinemia and type II diabetes in obesity patients and
      animals. Previously, we have identified RBP4 as a serum marker for ovarian
      cancer. Here we further explored the consequence of RBP4 upregulation in ovarian
      cancer cells and its molecular mechanism. RESULTS: Our results show that RBP4 is
      overexpressed in ovarian cancer cells to the same extent as in adipose tissues.
      The overexpression of RBP4 in ovarian cancer cells promotes cancer cell migration
      and proliferation. At molecular level, cancer progression factors MMP2 and MMP9
      are induced in response to RBP4 overexpression. We further investigated which
      signaling pathways are utilized by RBP4 to activate ovarian cancer cell
      migration. We found RhoA/Rock1 pathway is turned on and CyclinD1 is upregulated
      in RBP4 overexpressed cells. Inhibition of RhoA/Rock1 pathway reduces the RBP4
      induced MMP2 and MMP9 expression. The RBP4 action is depend on its associated
      ligand vitamin A/retinol acid (RA) and possibly involves similar pathways as for
      conferring insulin resistance. Moreover, we show that knockdown of RBP4
      significantly reduce cancer cell migration and proliferation as well as
      expressions of oncogenic factors. CONCLUSIONS: Our results indicated that RBP4
      can drive ovarian cancer cell migration and proliferation via RhoA/Rock1 and ERK
      pathway. It suggests that RBP4 act as a oncogene in ovarian cancer cells. Thus,
      RBP4 could be a molecular bridge between obesity and cancers and a potential
      target for treating obese cancer patients.

PMID- 29642916
TI  - Longitudinal measurement invariance and explanatory IRT models for adolescents'
      oral health-related quality of life.
AB  - BACKGROUND: Longitudinal invariance is a perquisite for a valid comparison of
      oral health-related quality of life (OHRQoL) scores over time. Item response
      theory (IRT) models can assess measurement invariance and allow better estimation
      of the associations between predictors and latent construct. By extending IRT
      models, this study aimed to investigate the longitudinal invariance of the two 8
      item short forms of the Child Perception Questionnaire (CPQ11-14) regression
      short form (RSF:8) and item-impact short form (ISF:8) and identify factors
      associated with adolescents' OHRQoL and its change. METHODS: All students from S1
      and S2 (equivalent to US grades 6 and 7) who were born in April 1997 and May 1997
      (at age 12) from 45 randomly selected secondary schools were invited to
      participate in this study and followed up after 3 years. Data on the CPQ11-14
      RSF:8 and CPQ11-14 ISF:8, demographics, oral health behavior and status were
      collected. Explanatory graded response models were fitted to both short forms of
      the CPQ11-14 data for assessing longitudinal invariance and factors associated
      with OHRQoL. The Bayesian estimation method - Monte Carlo Markov Chain (MCMC)
      with Gibbs sampling was adopted for parameter estimation and the credible
      intervals were used for inference. RESULTS: Data from 649 children at age 12 at
      baseline and 415 children at age 15 at follow up were analyzed. For the 12 years
      old children, healthier oral health behavior, better gum status, families with
      both parents employed and parents' education level were found to be associated
      with better OHRQoL. Four items among the 2 short forms lacked longitudinal
      invariance. With statistical adjustment of longitudinal invariance, OHRQoL were
      found improved in general over the 3 years but no predictor was associated with
      OHRQoL in follow-up. For those with decreased family income, their OHRQoL had
      worsened over 3 years. CONCLUSIONS: IRT explanatory analysis enables a more valid
      identification of the factors associated with OHRQoL and its changes over time.
      It provides important information to oral healthcare researchers and
      policymakers.

PMID- 29642917
TI  - Gender-specific association of serum uric acid levels and cardio-ankle vascular
      index in Chinese adults.
AB  - BACKGROUND: Little is known about the relationship between serum uric acid (SUA)
      and cardio-ankle vascular index (CAVI) in Chinese population. Therefore, we aimed
      to investigate the gender difference in the association of SUA and CAVI in a
      southwestern Chinese population. METHODS: Data were obtained from subjects via
      routine physical examinations in the Public Health Center of our hospital between
      2011 and 2014 in Chongqing. The data included completed anthropometry and blood
      biochemical indicators. The CAVI were recorded using an automatically VaseraVS
      1000 vascular screening system. RESULTS: We found females with hyperuricemia
      (HUA) had significantly higher CAVI than women with normal SUA (8.45 +/- 1.40 vs
      7.67 +/- 1.15, P<0.05). Then we defined high CAVI as CAVI>=9 m/s, and compared
      the percentage of high CAVI, we found women with HUA had higher percentage of
      high CAVI than women with normal SUA (26.83% vs 9.38%, P<0.05). Those differences
      were not significant in males. Also, the logistic regression analysis found age
      and hypertension were major independent risk factors associated with high CAVI in
      both genders. HUA and hyperglycemia were independently associated with high CAVI
      in females with an OR of 3.65, 95%CI (1.37-9.73) and 3.02, 95%CI (1.38-6.63)
      respectively. However, these significant associations were not be found in males.
      CONCLUSIONS: Our data showed positive associations between elevated SUA levels
      and higher CAVI risk in the inland Chinese females, but not in males. The reason
      for the gender differences were still unclear, sex hormones may play a role.
      Further prospective studies including detailed personal information and
      multicenter were required.

PMID- 29642918
TI  - The impact of osteoarthritis on early exit from work: results from a population
      based study.
AB  - BACKGROUND: Osteoarthritis (OA) is a leading cause of pain and disability, which
      may be a source of productivity losses. The objectives of this study were to
      describe the impact of OA, namely through pain and physical disability, on early
      exit from work and to calculate its economic burden. METHODS: We analysed data
      from the national, cross-sectional, population-based EpiReumaPt study (Sep2011
      Dec2013) in which 10,661 individuals were randomly surveyed in order to capture
      all cases of rheumatic diseases. We used all participants aged 50-64, near the
      official retirement age, who were clinically validated by experienced
      rheumatologists (n = 1286), including OA cases. A national database was used to
      calculate productivity values by gender, age and region, using the human capital
      approach. The impact of OA on the likelihood of early exit from work and the
      population attributable fractions used to calculate due economic burden (indirect
      costs) were obtained at the individual level by logistic regression. All results
      were based on weighted data. RESULTS: Almost one third of the Portuguese
      population aged 50-64 had OA (29.7%; men: 16.2% and women: 43.5%) and more than
      half were out of paid work (51.8%). Only knee OA is associated with early exit
      from work (OR: 2.25; 95%CI: 1.42-3.59; p = 0.001), whereas other OA locations did
      not reach any statistical difference. Furthermore, we observed an association
      between self-reported longstanding musculoskeletal pain (OR: 1.55; 95%CI: 1.07
      2.23; p = 0.02) and pain interference (OR: 1.35; 95%CI: 1.13-1.62; p = 0.001)
      with early exit from work. We also detected a clear relationship between levels
      of disability, measured by the Health Assessment Questionnaire (HAQ), and the
      probability of work withdrawal. The estimated annual cost of early exit from work
      attributable to OA was ?656 million (?384 per capita; ?1294 per OA patient and
      ?2095 per OA patient out-of-work). CONCLUSIONS: In this study, we observed an
      association between OA and early exit from work, largely dependent on pain and
      disability. This relationship translates into a meaningful economic burden
      amounting to approximately 0.4% of the national Gross Domestic Product (GDP). The
      high prevalence and the impact of this disabling chronic disease highlight the
      need to prioritize policies targeting early exit from work in OA.

PMID- 29642919
TI  - Simultaneous VENTANA IHC and RT-PCR testing of ALK status in Chinese non-small
      cell lung cancer patients and response to crizotinib.
AB  - BACKGROUND: ALK rearrangement-advanced NSCLC patients respond to crizotinib. ALK
      rearrangement is currently determined with RT-PCR. VENTANA IHC is a standard
      method to identify ALK protein overexpression in NSCLC; however, VENTANA IHC has
      rarely been used to determine the response to crizotinib in Chinese patients with
      NSCLC and ALK overexpression. To better clarify the clinical implication of
      VENTANA IHC to detect ALK rearrangements, we conducted this study to analyze
      VENTANA IHC and RT-PCR in a large cohort of Chinese patients with NSCLC
      undergoing screening for ALK rearrangements. METHODS: A total of 1720 patients
      with NSCLC who had ALK rearrangements detected by VENTANA IHC and/or RT-PCR were
      included in this analysis. We compared the efficacy and survival of ALK-positive
      patients detected by VENTANA IHC and RT-PCR. We used NGS to identify patients in
      whom the two methods were inconsistent. RESULTS: Among 1720 patients, 187
      (10.87%) were shown to be ALK-positive by VENTANA IHC and/or RT-PCR, and 66
      received crizotinib treatment. We identified 10.27% (172/1674) of patients as ALK
      positive by the VENTANA IHC method, and 12.73% (41/322) of patients had ALK
      rearrangements by the RT-PCR method. Twenty-nine of 276 (10.51%) ALK-positive
      patients were simultaneously analyzed using VENTANA IHC and RT-PCR. The overall
      response rates were 65.90% (29/44) by VENTANA IHC and 55.88% (19/34) by RT-PCR.
      The disease control rates were 86.36% (38/44) by VENTANA IHC and 76.47% (26/34)
      by RT-PCR. In contrast, the median progression-free survival for VENTANA IHC and
      RT-PCR was 8.5 and 9.2 months, respectively. The VENTANA IHC and RT-PCR results
      obtained for 6 of 17 ALK-positive patients were inconsistent based on NGS;
      specifically, 4 patients had EML4-ALK fusions, 2 patients had non EML4-ALK
      fusions, 1 patient had a KCL1-ALK fusion, and one patient had a FBXO36-ALK
      fusion. CONCLUSIONS: VENTANA IHC is a reliable and rapid screening tool used in
      routine pathologic laboratories for the identification of suitable candidates for
      ALK-targeted therapy. VENTANA IHC has moderate sensitivity and a slightly higher
      association with response to therapy with ALK inhibitors, and some VENTANA IHC
      positive, but RT-PCR-negative cases may benefit from crizotinib.

PMID- 29642920
TI  - Reverse shock index multiplied by Glasgow Coma Scale score (rSIG) is a simple
      measure with high discriminant ability for mortality risk in trauma patients: an
      analysis of the Japan Trauma Data Bank.
AB  - BACKGROUND: The shock index (SI), defined as heart rate (HR) divided by systolic
      blood pressure (SBP), is reported to be a more sensitive marker of shock than
      traditional vital signs alone. In previous literature, use of the reverse shock
      index (rSI), taken as SBP divided by HR, is recommended instead of SI for
      hospital triage. Among traumatized patients aged > 55 years, SI multiplied by age
      (SIA) might provide better prediction of early post-injury mortality. Separately,
      the Glasgow Coma Scale (GCS) score has been shown to be a very strong predictor.
      When considering these points together, rSI multiplied by GCS score (rSIG) or
      rSIG divided by age (rSIG/A) could provide even better prediction of in-hospital
      mortality. METHODS: This retrospective, multicenter study used data from 168,517
      patients registered in the Japan Trauma Data Bank for the period 2006-2015. We
      calculated areas under receiver operating characteristic curves (AUROCs) to
      measure the discriminant ability by comparing those of SI (or rSI), SIA, rSIG,
      and rSIG/A for in-hospital mortality and for 24-h blood transfusion. RESULTS: The
      highest ROC AUC (AUROC), 0.901(0.894-0.908) for in-hospital mortality in younger
      patients (aged < 55 years), was seen for rSIG. In older patients (aged >= 55
      years), the AUROC of rSIG/A, 0.845(0.840-0.850), was highest for in-hospital
      mortality. However, the difference between rSIG and rSIG/A was slight and did not
      seem to be clinically important. rSIG also had the highest AUROC of 0.745 (0.741
      749) for 24-h blood transfusion. CONCLUSIONS: rSIG ((SBP/HR) * GCS score) is easy
      to calculate without the need for additional information, charts or equipment,
      and can be a more reliable triage tool for identifying risk levels in trauma
      patients.

PMID- 29642921
TI  - Feasibility of robot-based perturbed-balance training during treadmill walking in
      a high-functioning chronic stroke subject: a case-control study.
AB  - BACKGROUND: For stroke survivors, balance deficits that persist after the
      completion of the rehabilitation process lead to a significant risk of falls. We
      have recently developed a balance-assessment robot (BAR-TM) that enables
      assessment of balancing abilities during walking. The purpose of this study was
      to test feasibility of using the BAR-TM in an experimental perturbed-balance
      training program with a selected high-functioning stroke survivor. METHODS: A
      control and an individual with right-side chronic hemiparesis post-stroke were
      studied. The individual post-stroke underwent thirty sessions of balance
      perturbed training that involved walking on an instrumented treadmill while the
      BAR-TM delivered random pushes to the participant's pelvis; these pushes were in
      various directions, at various speeds, and had various perturbation amplitudes.
      We assessed kinematics, kinetics, electromyography, and spatio-temporal responses
      to outward-directed perturbations of amplitude 60 N (before training) and 60 N
      and 90 N (after training) commencing on contact of either the nonparetic-left
      foot (LL-NP/L perturbation) or the paretic-right foot (RR-P/R perturbation) while
      the treadmill was running at a speed of 0.4 m/s. RESULTS: Before training, the
      individual post-stroke primarily responded to LL-NP/L perturbations with an in
      stance response on the non-paretic leg in a similar way to the control
      participant. After training, the individual post-stroke added adequate stepping
      by making a cross-step with the paretic leg that enabled successful rejection of
      the perturbation at lower and higher amplitudes. Before training, the individual
      post-stroke primarily responded to RR-P/R perturbations with fast cross-stepping
      using the left, non-paretic leg while in-stance response was entirely missing.
      After training, the stepping with the non-paretic leg was supplemented by
      partially recovered ability to exercise in-stance responses on the paretic leg
      and this enabled successful rejection of the perturbation at lower and higher
      amplitudes. The assessed kinematics, kinetics, electromyography, and spatio
      temporal responses provided insight into the relative share of each balancing
      strategy that the selected individual post-stroke used to counteract LL-NP/L and
      RR-P/R perturbations before and after the training. CONCLUSIONS: The main finding
      of this case-control study is that robot-based perturbed-balance training may be
      a feasible approach. It resulted in an improvement the selected post-stroke
      participant's ability to counteract outward-directed perturbations. TRIAL
      REGISTRATION: ClinicalTrials.gov Identifier: NCT03285919 - retrospectively
      registered.

PMID- 29642922
TI  - An anterolateral thigh chimeric flap for dynamic facial and esthetic
      reconstruction after oncological surgery in the maxillofacial region: a case
      report.
AB  - BACKGROUND: The surgical management of malignant tumors in the head and neck
      region often leads to functional and esthetic defects that impair the quality of
      life of the patients. Reconstruction can be solved with prostheses in these
      cases, but various types of microsurgical free flaps can provide a better
      clinical outcome. CASE PRESENTATION: In this case report, the tumor and parts of
      the involved facial muscles and nerve were excised surgically from a 42-year-old
      patient after a third relapse of basal cell carcinoma in the left midface. The
      tissue defect was reconstructed with an anterolateral thigh chimeric type I
      fascio-myocutaneous flap, where the facial palsy was restored with a segmental
      branch of the femoral nerve and the involved mouth corner elevator muscles for
      the segmented vastus lateralis muscle. The 6-month follow-up revealed a good
      esthetic outcome, the soft tissue defect reconstruction with good functional
      activity of the reconstructed facial nerve and with acceptable mimic movements.
      There has been no subsequent recurrence. CONCLUSIONS: It is concluded that the
      chimeric type I anterolateral fascio-myocutaneous free flap can offer a good
      option for the esthetic and functional reconstruction of an extensive tissue
      defect in the maxillofacial region.

PMID- 29642924
TI  - Cardiac output and CVP monitoring... to guide fluid removal.

PMID- 29642923
TI  - Association of maternal serum lipids at late gestation with the risk of neonatal
      macrosomia in women without diabetes mellitus.
AB  - BACKGROUND: Macrosomia is a serious public health problem worldwide due to its
      increasing prevalence and adverse influences on maternal and neonatal outcomes.
      Maternal dyslipidemia exerts potential and adverse impacts on pregnant women and
      newborns. However, the association between maternal serum lipids and the risk of
      macrosomia has not yet been clearly elucidated. We explored the association
      between the maternal lipids profile at late gestation and the risk of having
      macrosomia among women without diabetes mellitus (DM). METHODS: The medical
      records of 5407 pregnant women giving birth to single live babies at term were
      retrospectively analyzed. Subjects with DM, hypertension, thyroid disorders and
      fetal malformation were excluded. Maternal fasting serum lipids were measured
      during late pregnancy. Logistic regression analysis was used to analyze the
      variables associated with the risk of macrosomia. RESULTS: Maternal serum
      triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) levels were
      related to macrosomia; each 1 mmol/L increase in TG resulted in a 27% increase in
      macrosomia risk, while each 1 mmol/L increase in HDL-C level resulted in a 37%
      decrease in macrosomia risk, even after adjusting for potential confounders.
      Notably, the risk of macrosomia increased progressively with increased maternal
      serum TG levels and decreased HDL-C levels. Compared with women with serum TG
      levels < 2.5 mmol/L, women with TG levels greater than 3.92 mmol/L had an
      approximately 2.8-fold increased risk of macrosomia. Compared with women with
      serum HDL-C levels above 2.23 mmol/L, women with HDL-C levels of less than 1.62
      mmol/L had a 1.9-fold increased risk of giving birth to an infan with macrosomia.
      In addition, a higher risk of macrosomia was observed in women with simultaneous
      hypertriglyceridemia and low serum HDL-C levels (odds ratio [OR] 2.400, 95%
      confidence interval [CI]: 1.760-3.274) compared to those with
      hypertriglyceridemia or low serum HDL-C alone (OR 2.074, 95% CI: 1.609-2.673 and
      OR 1.363, 95% CI: 1.028-1.809, respectively). CONCLUSIONS: Maternal serum TG
      levels and HDL-C levels at late gestation are independent predictors of
      macrosomia in women without DM.

PMID- 29642925
TI  - Atypical traumatic anterior shoulder instability with excessive joint laxity:
      recurrent shoulder subluxation without a history of dislocation.
AB  - BACKGROUND: No previously published studies have examined recurrent traumatic
      incomplete events in patients with excessive joint laxity. The purpose of this
      study is to investigate outcomes after arthroscopic stabilization for recurrent
      traumatic shoulder subluxation in patients with excessive joint laxity but no
      history of dislocation. METHODS: This study included 23 patients with glenoid
      bone defects less than 20% who underwent arthroscopic stabilization of recurrent
      shoulder subluxation and were available for at least 2 years follow-up. Outcomes
      were assessed with the subjective shoulder value (SSV), University of California
      Los Angeles (UCLA) shoulder score, Rowe score, and sports/recreation activity
      level. RESULTS: Postoperatively, overall functional scores improved significantly
      (p <  0.001), compared to preoperative scores: SSV improved from 49.1 to 90.4;
      Rowe score improved from 36.7 to 90.2; and UCLA shoulder score improved from 26.3
      to 32.5. Patient satisfaction rate was 87% (20/23 patients). Sports/recreation
      activity level (return to premorbid activity level; grade I = 100% to grade IV =
      less than 70%) was grade I in 7 patients, grade II in 11, grade III in 3, grade
      IV in 2. The incidence of any glenoid bone defect was 61% (14/23 patients), and
      the mean glenoid bone defect size was 8%; among these 14 patients, 8 (35%)
      exhibited 15-20% glenoid bone defects. Instability reoccurred in 2 patients (9%)
      who had 15-20% glenoid bone defect. CONCLUSION: Despite excessive joint laxity,
      overall functional outcomes after arthroscopic stabilization of recurrent
      shoulder subluxation were satisfactory. However, arthroscopic Bankart repair may
      not be reliable in patients with excessive joint laxity plus a glenoid bone
      defect size of more than approximately 15%.

PMID- 29642926
TI  - Zidovudine ameliorates pathology in the mouse model of Duchenne muscular
      dystrophy via P2RX7 purinoceptor antagonism.
AB  - Duchenne muscular dystrophy (DMD) is the most common inherited muscle disorder
      that causes severe disability and death of young men. This disease is
      characterized by progressive muscle degeneration aggravated by sterile
      inflammation and is also associated with cognitive impairment and low bone
      density. Given that no current treatment can improve the long-term outcome,
      approaches with a strong translational potential are urgently needed. Duchenne
      muscular dystrophy (DMD) alters P2RX7 signaling in both muscle and inflammatory
      cells and inhibition of this receptor resulted in a significant attenuation of
      muscle and non-muscle symptoms in DMDmdx mouse model. As P2RX7 is an attractive
      target in a range of human diseases, specific antagonists have been developed.
      Yet, these will require lengthy safety testing in the pediatric population of
      Duchenne muscular dystrophy (DMD) patients. In contrast, Nucleoside Reverse
      Transcriptase Inhibitors (NRTIs) can act as P2RX7 antagonists and are drugs with
      an established safety record, including in children. We demonstrate here that AZT
      (Zidovudine) inhibits P2RX7 functions acting via the same allosteric site as
      other antagonists. Moreover, short-term AZT treatment at the peak of disease in
      DMDmdx mice attenuated the phenotype without any detectable side effects.
      Recovery was evident in the key parameters such as reduced sarcolemma
      permeability confirmed by lower serum creatine kinase levels and IgG influx into
      myofibres, decreased inflammatory cell numbers and inflammation markers in leg
      and heart muscles of treated mice. Moreover, this short-term therapy had some
      positive impact on muscle strength in vivo and no detrimental effect on
      mitochondria, which is the main side-effect of Nucleoside Reverse Transcriptase
      Inhibitors (NRTIs). Given these results, we postulate that AZT could be quickly
      re-purposed for the treatment of this highly debilitating and lethal disease.
      This approach is not constrained by causative DMD mutations and may be effective
      in alleviating both muscle and non-muscle abnormalities.

PMID- 29642927
TI  - Streptococcus bovis - unusual etiology of meningitis in a neonate with Down
      syndrome: a case report.
AB  - BACKGROUND: Common etiological agents of neonatal meningitis include group B
      Streptococcus, Escherichia coli, and Staphylococcus aureus. Here we report a rare
      pathogen - Streptococcus bovis - causing meningitis in a premature neonate with
      Down syndrome. CASE PRESENTATION: A 26-day-old Asian male neonate with Down
      syndrome presented with a history of high-grade fever, poor sucking, poor cry,
      and reduced activity. On admission, he was febrile and had features of
      circulatory collapse. A cerebrospinal fluid examination confirmed bacterial
      meningitis and blood culture isolated the causative organism: group D
      Streptococcus, which was verified as Streptococcus bovis biotype 2. An
      echocardiogram did not show evidence of infective endocarditis. CONCLUSIONS: This
      is probably the first report of neonatal meningitis due to Streptococcus bovis in
      a child with Down syndrome. Although our patient did not show features of overt
      immunodeficiency, subtle abnormalities in his immune system would have
      predisposed him to infection with this unusual organism. This case highlights the
      need for considering unusual pathogens when managing serious infections in
      children with Down syndrome.

PMID- 29642928
TI  - Diagnostic and management of life-threatening Adult-Onset Still Disease: a French
      nationwide multicenter study and systematic literature review.
AB  - BACKGROUND: Adult-onset Still disease (AOSD) is a rare systemic inflammatory
      disorder. A few patients develop organ complications that can be life
      threatening. Our objectives were to describe the disease course and phenotype of
      life-threatening AOSD, including response to therapy and long-term outcome.
      METHODS: A multicenter case series of intensive care medicine (ICU) patients with
      life-threatening AOSD and a systematic literature review. RESULTS: Twenty
      patients were included. ICU admission mostly occurred at disease onset (90%).
      Disease manifestations included fever (100%), sore throat (65%), skin rash (65%),
      and arthromyalgia (55%). Serum ferritin was markedly high (median: 29,110 ng/mL).
      Acute respiratory failure, shock and multiple organ failure occurred in 15 (75%),
      10 (50%), and 7 (35%) cases, respectively. Hemophagocytosis was demonstrated in
      eight cases. Two patients died. Treatment delay was significant. All patients
      received corticosteroids. Response rate was 50%. As second-line, intravenous
      immunoglobulins were ineffective. Anakinra was highly effective. After ICU
      discharge, most patients required additional treatment. Literature analysis
      included 79 cases of AOSD with organ manifestations, which mainly included
      reactive hemophagocytic syndrome (42%), acute respiratory failure (34%), and
      cardiac complications (23%). Response rate to corticosteroids was 68%. Response
      rates to IVIgs, cyclosporin, and anakinra were 50%, 80%, and 100%, respectively.
      CONCLUSIONS: AOSD should be recognized as a rare cause of sepsis mimic in
      patients with fever of unknown origin admitted to the ICU. The diagnosis relies
      on a few simple clinical clues. Early intensive treatment may be discussed. IVIgs
      should be abandoned. Long-term prognosis is favorable.

PMID- 29642929
TI  - How well does the minimum data set measure healthcare use? a validation study.
AB  - BACKGROUND: To improve care, planners require accurate information about nursing
      home (NH) residents and their healthcare use. We evaluated how accurately
      measures of resident user status and healthcare use were captured in the Minimum
      Data Set (MDS) versus administrative data. METHODS: This retrospective
      observational cohort study was conducted on all NH residents (N = 8832) from
      Winnipeg, Manitoba, Canada, between April 1, 2011 and March 31, 2013. Six study
      measures exist. NH user status (newly admitted NH residents, those who
      transferred from one NH to another, and those who died) was measured using both
      MDS and administrative data. Rates of in-patient hospitalizations, emergency
      department (ED) visits without subsequent hospitalization, and physician
      examinations were also measured in each data source. We calculated the
      sensitivity, specificity, positive and negative predictive values (PPV, NPV), and
      overall agreement (kappa, kappa) of each measure as captured by MDS using
      administrative data as the reference source. Also for each measure, logistic
      regression tested if the level of disagreement between data systems was
      associated with resident age and sex plus NH owner-operator status. RESULTS: MDS
      accurately identified newly admitted residents (kappa = 0.97), those who
      transferred between NHs (kappa = 0.90), and those who died (kappa = 0.95).
      Measures of healthcare use were captured less accurately by MDS, with high levels
      of both under-reporting and false positives (e.g., for in-patient
      hospitalizations sensitivity = 0.58, PPV = 0.45), and moderate overall agreement
      levels (e.g., kappa = 0.39 for ED visits). Disagreement was sometimes greater for
      younger males, and for residents living in for-profit NHs. CONCLUSIONS: MDS can
      be used as a stand-alone tool to accurately capture basic measures of NH use
      (admission, transfer, and death), and by proxy NH length of stay. As compared to
      administrative data, MDS does not accurately capture NH resident healthcare use.
      Research investigating these and other healthcare transitions by NH residents
      requires a combination of the MDS and administrative data systems.

PMID- 29642930
TI  - Neuropeptide regulation of adaptive immunity in the tibia fracture model of
      complex regional pain syndrome.
AB  - BACKGROUND: Both dysfunctional neuropeptide signaling and immune system
      activation are characteristic of complex regional pain syndrome (CRPS). Unknown
      is whether substance P (SP) or calcitonin gene-related peptide (CGRP) support
      autoantibody production and, consequently, nociceptive sensitization. METHODS:
      These experiments involved the use of a well-characterized tibia fracture model
      of CRPS. Mice deficient in SP expression (Tac1-/-) and CGRP signaling (RAMP1-/-)
      were used to probe the neuropeptide dependence of post-fracture sensitization and
      antibody production. The deposition of IgM in the spinal cord, sciatic nerves,
      and skin was followed using Western blotting, as was expression of the CRPS
      related autoantigen cytokeratin 16 (Krt16). Passive serum transfer to B-cell
      deficient muMT mice was used to assess the production of functional
      autoantibodies in CRPS model mice. The use of immunohistochemistry allowed us to
      assess neuropeptide-containing fiber distribution and Langerhans cell abundance
      in mouse and human CRPS patient skin, while Langerhans cell-deficient mice were
      used to assess the functional contributions of these cells. RESULTS: Functional
      SP and CGRP signaling were required both for the full development of nociceptive
      sensitization after fracture and the deposition of IgM in skin and neural
      tissues. Furthermore, the passive transfer of serum from wildtype but not
      neuropeptide-deficient mice to fractured muMT mice caused enhanced allodynia and
      postural unweighting. Langerhans cells were increased in number in the skin of
      fracture mice and CRPS patients, and those increases in mice were reduced in
      neuropeptide signaling-deficient animals. Unexpectedly, Langerhans cell-deficient
      mice showed normal nociceptive sensitization after fracture. However, the
      increased expression of Krt16 after tibia fracture was not seen in neuropeptide
      deficient mice. CONCLUSIONS: Collectively, these data support the hypothesis that
      neuropeptide signaling in the fracture limb of mice is required for autoantigenic
      IgM production and nociceptive sensitization. The mechanism may be related to
      neuropeptide-supported autoantigen expression.

PMID- 29642931
TI  - Bariatric surgery improves knee function and not knee pain in the early
      postoperative period.
AB  - BACKGROUND: Obesity remains the strongest predictor of knee osteoarthritis (OA).
      Studies have reported improvement in knee pain and function post-bariatric
      surgery secondary to weight loss and reduced mechanical loading, yet others found
      increased rates of total knee arthroplasty (TKA) in that patient population. To
      address this controversy, our study aimed to further assess the effect of
      surgically induced, "rapid" weight loss on knee pain and function. METHODS: Obese
      patients with chronic knee pain, who were undergoing bariatric surgery, were
      enrolled and surveyed preoperatively and 3 months postoperatively. Our outcome
      measures were knee pain and knee function, assessed by a knee injury and
      osteoarthritis outcome score (KOOS). The paired t test was used to compare pre-
      and postoperative KOOS scores. Pearson correlation coefficient was used to test
      the correlation between change in body mass index (BMI) with knee function, pain,
      and stiffness. RESULTS: A total of 30 patients was included in the study. The
      mean age was 35 years, with a mean preoperative BMI of 42.8. The mean difference
      in BMI at 3 months was 8.4 (SD3). There was a significant improvement in KOOS, -
      23.2 (+/- 20) points, p < 0.01, most pronounced in knee function related to sport
      activities, with a difference of - 22.6 points, p < 0.01. Knee pain scores
      improved but did not reach statistical significance. CONCLUSION: Surgically
      induced rapid weight loss significantly improved knee function, particularly
      related to sports. However, there was no change in knee pain. This may be related
      to increased high-impact knee exercises and reduced lean mass. Tailored exercise
      programs for bariatric surgery patients postoperatively, may improve symptoms and
      decrease the need for knee replacements in the long term.

PMID- 29642932
TI  - Early life swimming pool exposure and asthma onset in children - a case-control
      study.
AB  - BACKGROUND: Trichloramine exposure in indoor swimming pools has been suggested to
      cause asthma in children. We aimed to investigate the risk of asthma onset among
      children in relation to individual trichloramine exposure. METHODS: A
      longitudinal nested case-control study of 337 children with asthma (cases) and
      633 controls aged 16-17 years was performed within a population-based cohort from
      The Obstructive Lung Disease in Northern Sweden studies (OLIN). Year of asthma
      onset and exposure time at different ages were obtained in telephone interviews.
      Trichloramine concentrations in the pool buildings were measured. Skin prick test
      results for inhalant allergens were available from previous examinations of the
      cohort. The risk for asthma was analyzed in relation to the cumulative
      trichloramine exposure before onset of asthma. RESULTS: The participation rate
      was high in the original cohort (88 to 96%), and in the case-control study (80%).
      Trichloramine concentrations ranged from 0.020 to 0.55 mg/m3 (mean 0.15 mg/m3).
      Swimming pool exposure in early life was associated with a significantly higher
      risk of pre-school asthma onset. A dose-response relationship between swimming
      pool exposure and asthma was indicated in children with asthma onset at 1 year of
      age. Children who were both sensitized and exposed had a particularly high risk.
      CONCLUSIONS: Early life exposure to chlorinated swimming pool environments was
      associated with pre-school asthma onset.

PMID- 29642933
TI  - Impact of vitamin E and selenium on antioxidant capacity and lipid oxidation of
      cheddar cheese in accelerated ripening.
AB  - BACKGROUND: Ripening of cheddar cheese is a time taking process, duration of the
      ripening may be as long as one year. Long ripening time is a big hindrance in the
      popularity of cheese in developing countries. Further, energy resources in these
      countries are either insufficient or very expensive. Therefore, those methods of
      cheese ripening should be discovered which can significantly reduce the ripening
      time without compromising the quality characteristics of cheddar cheese. In
      accelerated ripening, cheese is usually ripened at higher temperature than
      traditional ripening temperatures. Ripening of cheddar cheese at high temperature
      with the addition of vitamin E and selenium is not previously studied. This
      investigation aimed to study the antioxidant activity of selenium and vitamin E
      in accelerated ripening using cheddar cheese as an oxidation substrate. METHODS:
      The ripening of cheddar cheese was performed at 18  degrees C and to prevent
      lipid oxidation, vitamin E and selenium were used alone and in combination. The
      treatments were as: cheddar cheese without any addition of vitamin E and selenium
      (T1), cheddar cheese added with 100 mg/kg vitamin E (T2), 200 mg/kg vitamin E
      (T3), 800 MUg/kg selenium (T4), 1200 MUg/kg selenium (T5), vitamin E 100 mg/kg +
      800 MUg/kg selenium (T6) and vitamin E 200 mg/kg + 1200 MUg/kg selenium (T7).
      Traditional cheddar cheese ripne ripened at 4-6  degrees C for 9 months was used
      as positive control. Cheese samples were ripened at 18  degrees C for a period of
      12 weeks and analyzed for chemical and oxidative stability characteristics at 0,
      6 and 12 weeks of storage. All these treatments were compared with a cheddar
      cheese without vitamin E, selenium and ripened at 4  degrees C or 12 weeks.
      Vacuum packaged cheddar cheese was ripened 18  degrees C for a period of 12 weeks
      and analyzed for chemical and oxidative stability characteristics at 0, 4 and 8
      weeks of storage period. RESULTS: Addition of Vitamin E and selenium did not have
      any effect on moisture, fat and protein content of cheddar cheese. After 6 weeks
      of ripening, total antioxidant capacity of T1, T2, T3, T4, T5, T6, T7 and
      standard cheese were 29.61%, 44.7%, 53.6%, 42.5%, 41.4%, 64.1%, 85.1% and 25.4%.
      After 6 weeks of ripening, reducing power of T1, T2, T3, T4, T5, T6, T7 and SC
      cheese were 14.7%, 18.1%, 26.3%, 19.2%, 25.3%, 33.4%, 40.3% and 11.6%. After 6
      weeks of ripening, 1, 1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging
      activity of T6 and T7 were 54.2% and 66.9%. While, DPPH free radical scavenging
      activity of T1 and standard cheese after 6 weeks of ripening were, 19.1 and
      18.5%, respectively. Free fatty acids of vitamin E and selenium supplemented, non
      supplemented and standard cheese were not significantly influenced from each
      other in 0, 6 and 12 weeks old cheddar cheese. Peroxide values of T1, T2, T3, T4,
      T5, T6, T7 and standard cheese after 6 weeks of accelerated ripening were 1.19,
      1.05, 0.88, 1.25, 0.29, 0.25, 0.24 and 0.28 (MeqO2/kg). After 6 weeks of
      ripening, anisidine value of T6 and T7 were 6.55 and 6.14. Conjugated dienes of
      T1, T2, T3, T4, T5, T6, T7 and standard cheese, after 6 weeks of accelerated
      ripening were 0.61, 0.55, 0.42, 0.77, 0.65, 0.17, 0.15 and 0.19. After 6 weeks of
      accelerated ripening, concentrations unsaturated fatty acids in T1, T2, T3, T4,
      T5, T6, T7 and standard cheese decreased by18.19%, 17.45%, 16.82%, 16.19%,
      12.71%, 8.48%, 6.92% and 14.71%. After 12 weeks of accelerated ripening,
      concentration of unsaturated fatty acids in T1, T2, T3, T4, T5, T6 and T7 and
      standard cheese decreased by 26.2%, 21.2%, 18.7%, 14.2%, 10.4%, 4.84%, 1.03% and
      6.78%. Cheddar cheese samples added with vitamin E, selenium and their
      combinations produced more organic acids during the ripening period of 12 weeks.
      After 6 and 12 weeks of ripening, flavor score of T6 and T7 was better than
      standard ripened cheddar cheese. CONCLUSIONS: After 6 weeks of accelerated
      ripening, sensory characteristics of T6 and T7 were similar to cheddar cheese
      that was ripened at 4  degrees C for 9 months. Ripening time of cheddar cheese
      may be reduced to 6 weeks by elevated temperature (18  degrees C) using vitamin E
      and selenium as antioxidants at T6 and T7 levels.

PMID- 29642934
TI  - Correlation of gene expression and associated mutation profiles of APOBEC3A,
      APOBEC3B, REV1, UNG, and FHIT with chemosensitivity of cancer cell lines to drug
      treatment.
AB  - BACKGROUND: The APOBEC gene family of cytidine deaminases plays important roles
      in DNA repair and mRNA editing. In many cancers, APOBEC3B increases the mutation
      load, generating clusters of closely spaced, single-strand-specific DNA
      substitutions with a characteristic hypermutation signature. Some studies also
      suggested a possible involvement of APOBEC3A, REV1, UNG, and FHIT in molecular
      processes affecting APOBEC mutagenesis. It is important to understand how
      mutagenic processes linked to the activity of these genes may affect sensitivity
      of cancer cells to treatment. RESULTS: We used information from the Cancer Cell
      Line Encyclopedia and the Genomics of Drug Sensitivity in Cancer resources to
      examine associations of the prevalence of APOBEC-like motifs and mutational loads
      with expression of APOBEC3A, APOBEC3B, REV1, UNG, and FHIT and with cell line
      chemosensitivity to 255 antitumor drugs. Among the five genes, APOBEC3B
      expression levels were bimodally distributed, whereas expression of APOBEC3A,
      REV1, UNG, and FHIT was unimodally distributed. The majority of the cell lines
      had low levels of APOBEC3A expression. The strongest correlations of gene
      expression levels with mutational loads or with measures of prevalence of APOBEC
      like motif counts and kataegis clusters were observed for REV1, UNG, and
      APOBEC3A. Sensitivity or resistance of cell lines to JQ1, palbociclib,
      bicalutamide, 17-AAG, TAE684, MEK inhibitors refametinib, PD-0325901, and
      trametinib and a number of other agents was correlated with candidate gene
      expression levels or with abundance of APOBEC-like motif clusters in specific
      cancers or across cancer types. CONCLUSIONS: We observed correlations of
      expression levels of the five candidate genes in cell line models with
      sensitivity to cancer drug treatment. We also noted suggestive correlations
      between measures of abundance of APOBEC-like sequence motifs with drug
      sensitivity in small samples of cell lines from individual cancer categories,
      which require further validation in larger datasets. Molecular mechanisms
      underlying the links between the activities of the products of each of the five
      genes, the resulting mutagenic processes, and sensitivity to each category of
      antitumor agents require further investigation.

PMID- 29642935
TI  - SP1-induced upregulation of lncRNA SPRY4-IT1 exerts oncogenic properties by
      scaffolding EZH2/LSD1/DNMT1 and sponging miR-101-3p in cholangiocarcinoma.
AB  - BACKGROUND: Accumulating evidence has indicated that long non-coding RNAs
      (lncRNAs) behave as a novel class of transcription products during multiple
      cancer processes. However, the mechanisms responsible for their alteration in
      cholangiocarcinoma (CCA) are not fully understood. METHODS: The expression of
      SPRY4-IT1 in CCA tissues and cell lines was determined by RT-qPCR, and the
      association between SPRY4-IT1 transcription and clinicopathologic features was
      analyzed. Luciferase reporter and chromatin immunoprecipitation (ChIP) assays
      were performed to explore whether SP1 could bind to the promoter region of SPRY4
      IT1 and activate its transcription. The biological function of SPRY4-IT1 in CCA
      cells was evaluated both in vitro and in vivo. ChIP, RNA binding protein
      immunoprecipitation (RIP) and luciferase reporter assays were performed to
      determine the molecular mechanism of SPRY4-IT1 in cell proliferation, apoptosis
      and invasion. RESULTS: SPRY4-IT1 was abnormally upregulated in CCA tissues and
      cells, and this upregulation was correlated with tumor stage and tumor node
      metastasis (TNM) stage in CCA patients. SPRY4-IT1 overexpression was also an
      unfavorable prognostic factor for patients with CCA. Additionally, SP1 could bind
      directly to the SPRY4-IT1 promoter region and activate its transcription.
      Furthermore, SPRY4-IT1 silencing caused tumor suppressive effects via reducing
      cell proliferation, migration and invasion; inducing cell apoptosis and reversing
      the epithelial-to-mesenchymal transition (EMT) process in CCA cells.
      Mechanistically, enhancer of zeste homolog 2 (EZH2) along with the lysine
      specific demethylase 1 (LSD1) or DNA methyltransferase 1 (DNMT1) were recruited
      by SPRY4-IT1, which functioned as a scaffold. Importantly, SPRY4-IT1 positively
      regulated the expression of EZH2 through sponging miR-101-3p. CONCLUSIONS: Our
      data illustrate how SPRY4-IT1 plays an oncogenic role in CCA and may offer a
      potential therapeutic target for treating CCA.

PMID- 29642936
TI  - Detection of titanium particles in human liver and spleen and possible health
      implications.
AB  - BACKGROUND: Titanium dioxide (TiO2) is produced at high volumes and applied in
      many consumer and food products. Recent toxicokinetic modelling indicated the
      potential of TiO2 to accumulate in human liver and spleen upon daily oral
      exposure, which is not routinely investigated in chronic animal studies. A health
      risk from nanosized TiO2 particle consumption could not be excluded then.
      RESULTS: Here we show the first quantification of both total titanium (Ti) and
      TiO2 particles in 15 post-mortem human livers and spleens. These low-level
      analyses were enabled by the use of fully validated (single particle) inductively
      coupled plasma high resolution mass spectrometry ((sp)ICP-HRMS) detection methods
      for total Ti and TiO2 particles. The presence of TiO2 in the particles in tissues
      was confirmed by Scanning Electron Microscopy with energy dispersive X-ray
      spectrometry. CONCLUSIONS: These results prove that TiO2 particles are present in
      human liver and spleen, with >=24% of nanosize (< 100 nm). The levels are below
      the doses regarded as safe in animals, but half are above the dose that is deemed
      safe for liver damage in humans when taking into account several commonly applied
      uncertainty factors. With these new and unique human data, we remain with the
      conclusion that health risks due to oral exposure to TiO2 cannot be excluded.

PMID- 29642937
TI  - Evaluation of a simple polytetrafluoroethylene (PTFE)-based membrane for blood
      feeding of malaria and dengue fever vectors in the laboratory.
AB  - BACKGROUND: Controlled blood-feeding is essential for maintaining laboratory
      colonies of disease-transmitting mosquitoes and investigating pathogen
      transmission. We evaluated a low-cost artificial feeding (AF) method, as an
      alternative to direct human feeding (DHF), commonly used in mosquito
      laboratories. METHODS: We applied thinly-stretched pieces of
      polytetrafluoroethylene (PTFE) membranes cut from locally available seal tape
      (i.e. plumbers tape, commonly used for sealing pipe threads in gasworks or
      waterworks). Approximately 4 ml of bovine blood was placed on the bottom surfaces
      of inverted Styrofoam cups and then the PTFE membranes were thinly stretched over
      the surfaces. The cups were filled with boiled water to keep the blood warm (~37 
      degrees C), and held over netting cages containing 3-4 day-old inseminated adults
      of female Aedes aegypti, Anopheles gambiae (s.s.) or Anopheles arabiensis. Blood
      feeding success, fecundity and survival of mosquitoes maintained by this system
      were compared against DHF. RESULTS: Aedes aegypti achieved 100% feeding success
      on both AF and DHF, and also similar fecundity rates (13.1 +/- 1.7 and 12.8 +/-
      1.0 eggs/mosquito respectively; P > 0.05). An. arabiensis had slightly lower
      feeding success on AF (85.83 +/- 16.28%) than DHF (98.83 +/- 2.29%) though these
      were not statistically different (P > 0.05), and also comparable fecundity
      between AF (8.82 +/- 7.02) and DHF (8.02 +/- 5.81). Similarly, for An. gambiae
      (s.s.), we observed a marginal difference in feeding success between AF (86.00 +/
      10.86%) and DHF (98.92 +/- 2.65%), but similar fecundity by either method.
      Compared to DHF, mosquitoes fed using AF survived a similar number of days
      [Hazard Ratios (HR) for Ae. aegypti = 0.99 (0.75-1.34), P > 0.05; An. arabiensis
      = 0.96 (0.75-1.22), P > 0.05; and An. gambiae (s.s.) = 1.03 (0.79-1.35), P >
      0.05]. CONCLUSIONS: Mosquitoes fed via this simple AF method had similar feeding
      success, fecundity and longevity. The method could potentially be used for
      laboratory colonization of mosquitoes, where DHF is unfeasible. If improved (e.g.
      minimizing temperature fluctuations), the approach could possibly also support
      studies where vectors are artificially infected with blood-borne pathogens.

PMID- 29642938
TI  - Social network correlates of risky sexual behavior among adolescents in Bahir Dar
      and Mecha Districts, North West Ethiopia: an institution-based study.
AB  - BACKGROUND: Behaviors established during adolescence such as risky sexual
      behaviors have negative effects on future health and well-being. Extant
      literature indicated that individual attributes such as peer pressure and
      substance use have impacts on healthy development of young peoples' sexual
      behavior. The patterns of relationships (social network structure) and the social
      network content (members' norm regarding sexual practice) established by
      adolescents' network on adolescents' risky sexual behaviors are not well
      investigated. METHODS: This cross-sectional study assessed the roles of social
      networks on sexual behavior of high school adolescents in Bahir Dar and Mecha
      district, North West Ethiopia. Data were collected from 806 high school
      adolescents using a pretested anonymously self administered questionnaire.
      Hierarchical logistic regression model was used for analysis. RESULTS: The
      results indicated that more than 13% had risky sexual behavior. Taking social
      networks into account improved the explanation of risky sexual behavior over
      individual attributes. Adolescents embedded within increasing sexual practice
      approving norm (AOR 1.61; 95%CI: 1.04 - 2.50), increasing network tie strength
      (AOR 1.12; 95% CI: 1.06 - 1.19), and homogeneous networks (AOR 1.58; 95% CI: .98 
      2.55) were more likely to had risky sexual behavior. Engaging within increasing
      number of sexuality discussion networks was found protective of risky sexual
      behavior (AOR .84; 95% CI: .72 - .97). CONCLUSION: Social networks better predict
      adolescent's risky sexual behavior than individual attributes. The findings
      indicated the circumstances or contexts that social networks exert risks or
      protective effects on adolescents' sexual behavior. Programs designed to reduce
      school adolescents' sexual risk behavior should consider their patterns of social
      relationships.

PMID- 29642939
TI  - Elimination of onchocerciasis from Colombia: first proof of concept of river
      blindness elimination in the world.
AB  - BACKGROUND: Onchocerciasis is a chronic parasitic infection originally endemic in
      13 discrete regional foci distributed among six countries of Latin America
      (Brazil, Colombia, Ecuador, Guatemala, Mexico and Venezuela). In Colombia, this
      disease was discovered in 1965 in the Pacific Coast of the country. The National
      Onchocerciasis Elimination Program was established in 1993 with the aim of
      eliminating disease morbidity and infection transmission. In 2013, the World
      Health Organization (WHO) verified Colombia as free of onchocerciasis, becoming
      the first country in the world to reach such a goal. This report provides the
      empirical evidence of the elimination of Onchocerca volvulus transmission by
      Simulium exiguum (s.l.) after 12 years of 6-monthly mass drug administration of
      Mectizan(r) (ivermectin) to all the eligible residents living in this endemic
      area. METHODS: From 1996 onwards, a biannual community-based mass ivermectin
      administration programme was implemented, complemented by health education and
      community participation. In-depth parasitological, serological and entomological
      surveys were conducted periodically between 1998 and 2007 to evaluate the impact
      of ivermectin treatment according to the 2001 WHO guidelines. When the
      interruption of parasite transmission was demonstrated, the drug distribution
      ceased and a three-year post-treatment surveillance (PTS) period (2008-2010) was
      initiated. RESULTS: After 23 rounds of treatment, parasitological and
      ophthalmological assessments showed absence of microfilariae in skin and anterior
      chamber of the eyes. Serological tests proved lack of antibodies against O.
      volvulus in children under 10 years-old. A total of 10,500 S. exiguum flies
      tested by PCR had no L3 infection (infectivity rate = 0.0095%; 95% CI: 0.0029
      0.049) during 2004, indicating interruption of parasite transmission. However,
      biannual ivermectin treatments continued until 2007 followed by a 3-year PTS
      period at the end of which 13,481 flies were analyzed and no infective flies were
      found (infectivity rate = 0%; 95% CI: 0.0-0.014). CONCLUSIONS: These results
      fulfilled the WHO criteria for onchocerciasis elimination. Consequently, in 2013
      Colombia was verified as free of onchocerciasis, demonstrating that elimination
      of this neglected tropical disease is an achievable goal and paving the way for
      an elimination agenda to be followed by other endemic countries in Latin America
      and Africa.

PMID- 29642940
TI  - Multi-cohort analysis of colorectal cancer metagenome identified altered bacteria
      across populations and universal bacterial markers.
AB  - BACKGROUND: Alterations of gut microbiota are associated with colorectal cancer
      (CRC) in different populations and several bacterial species were found to
      contribute to the tumorigenesis. The potential use of gut microbes as markers for
      early diagnosis has also been reported. However, cohort specific noises may
      distort the structure of microbial dysbiosis in CRC and lead to inconsistent
      results among studies. In this regard, our study targeted at exploring changes in
      gut microbiota that are universal across populations at species level. RESULTS:
      Based on the combined analysis of 526 metagenomic samples from Chinese, Austrian,
      American, and German and French cohorts, seven CRC-enriched bacteria (Bacteroides
      fragilis, Fusobacterium nucleatum, Porphyromonas asaccharolytica, Parvimonas
      micra, Prevotella intermedia, Alistipes finegoldii, and Thermanaerovibrio
      acidaminovorans) have been identified across populations. The seven enriched
      bacterial markers classified cases from controls with an area under the receiver
      operating characteristics curve (AUC) of 0.80 across the different populations.
      Abundance correlation analysis demonstrated that CRC-enriched and CRC-depleted
      bacteria respectively formed their own mutualistic networks, in which the latter
      was disjointed in CRC. The CRC-enriched bacteria have been found to be correlated
      with lipopolysaccharide and energy biosynthetic pathways. CONCLUSIONS: Our study
      identified potential diagnostic bacterial markers that are robust across
      populations, indicating their potential universal use for non-invasive CRC
      diagnosis. We also elucidated the ecological networks and functional capacities
      of CRC-associated microbiota.

PMID- 29642941
TI  - Exosomal miRNAs in hepatocellular carcinoma development and clinical responses.
AB  - Hepatocellular carcinoma remains the sixth most lethal malignancy in the world.
      While HCC is often diagnosed via current biomarkers at a late stage, early
      detection of HCC has proven to be very difficult. Recent studies have focused on
      using exosomal miRNAs in clinical diagnostics and therapeutics, because they have
      improved stability in exosomes than as free miRNAs themselves. Exosomal miRNAs
      act through novel mechanisms for inducing cellular responses in a variety of
      biological circumstances. Dysregulated expression of miRNAs in exosomes can also
      accelerate HCC progression, including cell proliferation and metastasis, via
      alteration of a network of genes. Growing evidence demonstrates that exosomal
      miRNAs can affect many aspects of physiological and pathological conditions in
      HCC and indicates that miRNAs in exosomes can not only serve as sensitive
      biomarkers for cancer diagnostics and recurrence but can also potentially be used
      as therapeutics to target HCC progression. In this review, we summarize the
      latest findings between exosomal miRNAs and HCC, in order to better comprehend
      the functions and applications in HCC. Moreover, we discuss critical issues to
      consider when developing anti-tumor exosomal miRNAs as a novel therapeutic
      strategy for treating HCC in the clinic.

PMID- 29642942
TI  - Molecular identification of badger-associated Babesia sp. DNA in dogs: updated
      phylogeny of piroplasms infecting Caniformia.
AB  - BACKGROUND: Piroplasms are unicellular, tick-borne parasites. Among them, during
      the past decade, an increasing diversity of Babesia spp. has been reported from
      wild carnivores. On the other hand, despite the known contact of domestic and
      wild carnivores (e.g. during hunting), and a number of ixodid tick species they
      share, data on the infection of dogs with babesiae from other families of
      carnivores are rare. METHODS: In this study blood samples were collected from 90
      dogs and five road-killed badgers. Ticks were also removed from these animals.
      The DNA was extracted from all blood samples, and from 33 ticks of badgers,
      followed by molecular analysis for piroplasms with PCR and sequencing, as well as
      by phylogenetic comparison of detected genotypes with piroplasms infecting
      carnivores. RESULTS: Eleven of 90 blood DNA extracts from dogs, and all five
      samples from badgers were PCR-positive for piroplasms. In addition to the
      presence of B. canis DNA in five dogs, sequencing identified the DNA of badger
      associated "Babesia sp. Meles-Hu1" in six dogs and in all five badgers. The DNA
      of "Babesia sp. Meles-Hu1" occurred significantly more frequently in dogs often
      taken to forests (i.e. the preferred habitat of badgers in Hungary), than in dogs
      without this characteristic. Moreover, detection of DNA from this Babesia sp. was
      significantly associated with hunting dogs in comparison with dogs not used for
      hunting. Two PCR-positive dogs (in one of which the DNA of the badger-associated
      Babesia sp. was identified, whereas in the other the DNA of B. canis was present)
      showed clinical signs of babesiosis. Engorged specimens of both I. canisuga and
      I. hexagonus were collected from badgers with parasitaemia, but only I. canisuga
      contained the DNA of "Babesia sp. Meles-Hu1". This means a significant
      association of the DNA from "Babesia sp. Meles-Hu1" with I. canisuga.
      Phylogenetically, "Babesia sp. Meles-Hu1" belonged to the "B. microti" group.
      CONCLUSIONS: This is the first detection of the DNA from a badger-associated
      Babesia sp. in dogs, one of which also showed relevant clinical signs. Based on
      the number of dogs with blood samples containing the DNA of "Babesia sp. Meles
      Hu1" in this study (i.e. exceeding the number of B. canis-positives), these
      findings should not be regarded as isolated cases. It is assumed that dogs, which
      are used for hunting or frequently visit forests, are more likely to be exposed
      to this piroplasm, probably as a consequence of infestation with I. canisuga from
      badgers or from the burrows of badgers. The above results suggest that "Babesia
      sp. Meles-Hu1" should be added to the range of piroplasms, which are naturally
      capable of infecting hosts from different families of Caniformia.

PMID- 29642943
TI  - Celiac axis stenosis due to median arcuate ligament compression in a patient who
      underwent pancreatoduodenectomy; intraoperative assessment of hepatic arterial
      flow using Doppler ultrasonography: a case report.
AB  - BACKGROUND: Celiac axis stenosis due to compression by the median arcuate
      ligament has been reported in patients undergoing pancreaticoduodenectomy; it
      leads to the development of major collateral pathways that feed the hepatic
      artery. Dividing these important collaterals during pancreaticoduodenectomy can
      cause ischemic complications which may lead to a high mortality rate. To prevent
      these complications, it is necessary to assess intrahepatic arterial flow. CASE
      PRESENTATION: A 71-year-old Japanese man with anorexia was referred to us for the
      treatment of alcoholic chronic pancreatitis. Computed tomography revealed a
      pancreatic head tumor with a calculus, associated with the dilatation of the main
      pancreatic duct and intrahepatic bile duct. Three-dimensional imaging
      demonstrated focal narrowing in the proximal celiac axis due to median arcuate
      ligament compression and a prominent gastroduodenal artery that fed the common
      hepatic artery. The preoperative diagnosis was alcoholic chronic pancreatitis
      with common bile duct obstruction and celiac axis stenosis due to median arcuate
      ligament compression. Pancreaticoduodenectomy with median arcuate ligament
      release was scheduled. Before the division of the median arcuate ligament, the
      peak flow velocity and resistive index of his intrahepatic artery measured with
      Doppler ultrasonography decreased from 37.7 cm/second and 0.510, respectively, to
      20.6 cm/second and 0.508 respectively, when his gastroduodenal artery was
      clamped. However, these values returned to baseline levels after the division of
      the median arcuate ligament. These findings suggested that
      pancreaticoduodenectomy could be performed safely. Our patient was discharged on
      postoperative day 17 without significant complications. CONCLUSION: The
      intraoperative quantitative evaluation of intrahepatic arterial blood flow using
      Doppler ultrasonography was useful in a patient who underwent
      pancreaticoduodenectomy, who had celiac axis stenosis due to compression by the
      median arcuate ligament.

PMID- 29642944
TI  - Concomitant visceral and localized cutaneous leishmaniasis in two Moroccan
      infants.
AB  - BACKGROUND: Leishmaniases are vector-borne diseases caused by the protozoa of the
      Leishmania genus. The clinical spectrum of these diseases extends from benign
      dermal lesions to visceral forms. In the Mediterranean region, zoonotic visceral
      leishmaniasis (ZVL) is caused by L. infantum. If untreated within two years, the
      disease usually leads to death. In Morocco, ZVL is endemic in the north, with a
      hundred cases notified each year, mostly in children aged below five years. Here,
      we report on two clinical observations in infants presenting unusual concomitant
      VL and cutaneous leishmaniasis (CL) in Morocco. CASE PRESENTATION: In this case
      study, we report on two infants aged nine and 12 months old. They both have a
      history of febrile splenomegaly, anemia, and pallor of mucous membranes. Visceral
      leishmaniasis was confirmed by parasitological diagnosis (positive bone marrow
      smear and screening of anti-L. infantum antibodies). However, the clinical
      examination also showed cutaneous lesions that suggested the presence of CL. This
      was reinforced by the patients having a history of living or traveling to endemic
      foci. Thus, direct examination, culture, and PCR-RFLP (ITS1-Hae 3) were carried
      out on the patients' dermal exudates. In one of the infants, CL was associated
      with L. infantum, while in the other it was associated with L. tropica. The
      infants were treated as according to the recommendations of the Ministry of
      Health. Both patients were cured in two months; defervescence, reduction of
      splenomegaly, and healing of cutaneous lesions were all observed. CONCLUSIONS:
      These singular patients illustrate the clinical polymorphism of CL and the
      necessity of updating the differential diagnosis of leukemia-like syndromes,
      including VL, in children living in or travelling to known endemic areas. These
      observations suggest a change in the Mediterranean VL phenotype that may be
      associated with CL.

PMID- 29642945
TI  - RNA sequencing of murine mammary epithelial stem-like cells (HC11) undergoing
      lactogenic differentiation and its comparison with embryonic stem cells.
AB  - OBJECTIVES: Understanding of transcriptional networks specifying HC11 murine
      mammary epithelial stem cell-like cells (MEC) in comparison with embryonic stem
      cells (ESCs) and their rewiring, under the influence of glucocorticoids (GC) and
      prolactin (PRL) hormones, is critical for elucidating the mechanism of
      lactogenesis. In this data note, we provide RNA sequencing data from murine MECs
      and ESCs, MECs treated with steroid hormone alone and in combination with PRL.
      This data could help in understanding temporal dynamics of mRNA transcription
      that impact the process of lactogenesis associated with mammary gland
      development. Further integration of these data sets with existing datasets of
      cells derived from various stages of mammary gland development and different
      types of breast tumors, should pave the way for effective prognosis and to
      develop therapies for breast cancer. DATA DESCRIPTION: We have generated RNA
      sequencing data representing steady-state levels of mRNAs from murine ESCs,
      normal MECs (N), MECs primed (P) with hydrocortisone (HC) alone and in
      combination with PRL hormone by using Illumina sequencing platform. We have
      generated ~ 58 million reads for ESCs with an average length of ~ 100 nt and an
      average 115 million good quality mapped reads with an average length of ~ 150 nt
      for different stages of MECs differentiation.

PMID- 29642946
TI  - Correction to: identification of multiple cancer-associated myositis-specific
      autoantibodies in idiopathic inflammatory myopathies: a large longitudinal cohort
      study.
AB  - After publication of the article [1], it has been brought to our attention that
      the labels in Fig. 2b have been switched and are as a result incorrect. The label
      for the red line should have the label "non-CAM" and the yellow line "CAM".

PMID- 29642947
TI  - Absence of flexor carpi radialis identified during volar approach for fixation of
      distal radius fracture: a case report.
AB  - BACKGROUND: Volar locking plate fixation of distal radius fractures is commonly
      performed because of its good clinical outcomes. The flexor carpi radialis (FCR)
      approach is one of the most popular approaches to dissecting the volar side of
      the distal radius because of its simplicity and safety. We describe an extremely
      rare case of an absent FCR identified during a volar approach for fixation of a
      distal radius fracture. CASE PRESENTATION: A 59-year-old woman with distal radius
      fracture underwent surgery using the usual FCR approach and volar locking plate.
      We could not identify the absence of the FCR tendon preoperatively because of
      severe swelling of the distal forearm. At first, we wrongly identified the
      palmaris longus tendon as the FCR because it was the tendinous structure at the
      most radial location of the volar distal forearm. When we found the median nerve
      just radial to the palmaris longus tendon, we were then able to identify the
      anatomical abnormality in this case. To avoid iatrogenic neurovascular injuries,
      we changed the approach to the classic Henry's approach. CONCLUSIONS: Although
      the FCR approach is commonly used for fixation of distal radius fractures because
      of its simplicity and safety, this is the first report of complete absence of the
      FCR during the commonly performed volar approach for fixation of a distal radius
      fracture, to our knowledge. Because the FCR is designated as a favorable landmark
      because of its superficially palpable location, strong and thick structure, and
      rare anatomical variations, there is the possibility of iatrogenic complications
      in cases of the absence of the FCR. We suggest that surgeons should have a
      detailed knowledge of the range of possible anomalies to complete the fixation of
      a distal radius fracture safely.

PMID- 29642948
TI  - Sex and interleukin-6 are prognostic factors for autoimmune toxicity following
      treatment with anti-CTLA4 blockade.
AB  - BACKGROUND: Ipilimumab is a licensed immunotherapy for metastatic melanoma
      patients and, in the US, as adjuvant treatment for high risk melanoma radically
      resected. The use of ipilimumab is associated with a typical but unpredictable
      pattern of side effects. The purpose of this study was to identify clinical
      features and blood biomarkers capable of predicting ipilimumab related toxicity.
      METHODS: We performed a prospective study aimed at analyzing potential clinical
      and biological markers associated with immune-related toxicity in patients
      treated with ipilimumab (3 mg/kg, q3w). We enrolled 140 consecutive melanoma
      patients treated with ipilimumab for metastatic disease. The following
      prospectively collected data were utilized: patient characteristics, previous
      therapies, level of circulating biomarkers associated with tumour burden or
      immune-inflammation status (lactic dehydrogenase, C-reactive protein, beta2
      microglobulin, vascular endothelial growth factor, interleukin-2, interleukin-6,
      S-100, alkaline phosphatase, transaminases) and blood cells subsets (leukocyte
      and lymphocyte subpopulations). Logistic regression was used for multivariate
      analysis of data. RESULTS: Out of 140 patients, 36 (26%) experienced a severe
      adverse event, 33 (24%) discontinued treatment for severe toxicity. Among the
      immune-profile biomarkers analyzed, only interleukin-6 was associated with the
      risk of toxicity. Female patients had a further increase of immune-related
      adverse events. Low baseline interleukin-6 serum levels (OR = 2.84, 95% CI 1.34
      6.03, P = 0.007) and sex female (OR = 1.5, 95% CI 1.06-2.16 P = 0.022) and were
      significant and independent risk factors for immune related adverse events.
      CONCLUSIONS: Baseline IL6 serum levels and female sex were significantly and
      independently associated with higher risk of severe toxicity and could be
      exploited in clinical practice to personalize toxicity surveillance in patients
      treated with ipilimumab.

PMID- 29642949
TI  - Estimated frailty prevalence among Israeli elderly - results from a cross
      sectional national survey.
AB  - BACKGROUND: Increasing longevity presents new social and medical challenges in
      developed countries. The prevalence of frailty is of interest because of its
      association with health prognosis and outcomes, but so far there is no single
      best diagnostic tool for this entity. Therefore, estimated prevalence of frailty
      in countries varies considerably and ranges between 5% and 58%. In Israel, the
      nation-wide prevalence of frailty in the elderly population is presently unknown.
      The objective of our study was to assess the rate of the frailty in elderly
      Israelis. METHODS: A post-hoc analysis based on the results of a national Health
      and Nutrition Survey in Israeli elderly (MABAT Zahav). A non-direct model to
      estimate frailty was based on five components that were most similar to the
      common frailty assessment suggested by Morley et al. The frailty state was then
      reclassified according to different explanatory variables. RESULTS: Data
      collected from 1619 subjects (F/M = 52.9/47.1%) with an average age of 74.6 years
      were analyzed. Estimated frailty prevalence in the elderly population was 4.9%.
      Frail people were more likely to have a lower income, be unemployed and have a
      lower education level. Frailty rates were higher in women, in Jews and in
      subjects more prone to low physical function. CONCLUSIONS: The estimated frailty
      prevalence in the Israeli elderly population, while relatively low, is comparable
      to some of the rates suggested in the literature. The factors associated with
      frailty in the Israeli population are in accordance with the existing literature.
      The suggested model may be helpful in identifying frailty in Israeli elderly.

PMID- 29642950
TI  - Melliferous insects and the uses assigned to their products in the northern
      Yungas of Salta, Argentina.
AB  - BACKGROUND: The order Hymenoptera comprises melliferous insects (bees, wasps and
      bumblebees); among them, stingless bees comprise a diverse group of eusocial
      insects present in tropical and subtropical areas. Of a total of approximately
      500 species, 400 are found in the Neotropics. On the continent of America, before
      the introduction of Apis mellifera, these insects represented the main source of
      honey and wax. In Argentina, ethnobiological investigations had been carried out
      on this group of insects, principally in the Atlantic Forest and Chaco regions.
      Out of a total of 33 species, only 14 were recorded for use or breeding. In the
      Yungas, however, there are no ethnobiological studies analyzing this group of
      species, although the use of their products is mentioned in different
      ethnobotanical works. This paper studies the knowledge and uses of melliferous
      insects by the inhabitants of the village of Baritu and surrounding. METHOD:
      Information on location, management and duties assigned (e.g., preparation and
      administration) to deal with bee products like honey, pollen, wax and propolis
      was obtained through semi-structured interviews. Besides, reference material was
      collected to identify melliferous insects known and used in the region. RESULTS:
      Fifteen ethnospecies were identified and grouped locally according to their
      defensive behavior. The culturally most important species is the stingless bee
      Plebeia sp. nov.-mansita-, in terms of frequency of citations and diversity of
      uses, and among those that sting, the honeybee Apis mellifera-extranjera-. Honey,
      pollen, wax, and propolis of Plebeia sp. nov. had the highest current frequency
      of use. Honey is used in food (incorporated at pure state, as a complement and in
      drinks), as nutraceutical food and in medicinal preparations. In addition, it is
      an important resource for marketing during the warm season, infusions being the
      main mode of administration. Pollen is used as a supplement for food and
      alcoholic drinks, wax mainly in candle making, and propolis. CONCLUSION: The data
      obtained in this study complements the information available in ethnobotanical
      studies carried out in the region. The present study is the first on melliferous
      insects in the area. A new species of stingless bee the genus Plebeia was
      registered, and it was observed that the known distribution of others has
      increased.

PMID- 29642951
TI  - Use of oxidized regenerated cellulose to achieve hemostasis during laparoscopic
      cholecystectomy: a retrospective cohort analysis.
AB  - OBJECTIVE: Laparoscopic cholecystectomy is the first-choice treatment for
      symptomatic cholelithiasis. Though generally safe, this procedure is not without
      complications, with bleeding the most frequent cause of conversion to open
      cholecystectomy. Oxidized regenerated cellulose (ORC) added to conventional
      hemostatic strategies, is widely used to control bleeding during surgery despite
      limited evidence supporting its use. This retrospective study analyzed patients
      undergoing laparoscopic cholecystectomy in an Italian center over a 16-month
      period, between October 2014 and February 2016, who experienced uncontrollable
      bleeding despite the use of conventional hemostatic strategies, requiring the
      addition of ORC gauze (Emosist(r)). RESULTS: Of the 530 patients who underwent
      laparoscopic cholecystectomy, 24 (4.5%) had uncontrollable bleeding from the
      liver bed. Of these, 62.5% had acute cholecystitis and 33.3% chronic
      cholecystitis; 1 patient was diagnosed with gallbladder carcinoma,
      postoperatively. Most patients had comorbidities, 16.7% had liver cirrhosis, and
      37.5% used oral anticoagulants. The application of ORC rapidly controlled
      bleeding in all patients. Patients were discharged after a mean duration of 2.2
      days. ORC was easy to use and well tolerated. Bleeding complications remain a
      relevant issue in laparoscopic cholecystectomy. ORC was able to promptly stop
      bleeding not adequately controlled by conventional methods and appears,
      therefore, to be a useful hemostat.

PMID- 29642952
TI  - Recombinase polymerase amplification assay combined with a lateral flow dipstick
      for rapid detection of Tetracapsuloides bryosalmonae, the causative agent of
      proliferative kidney disease in salmonids.
AB  - BACKGROUND: The myxozoan Tetracapsuloides bryosalmonae, the causative agent of
      proliferative kidney disease (PKD), is responsible for considerable losses in
      farmed and wild fish populations in Europe and North America. Recently, T.
      bryosalmonae was detected in many European countries, and strategy to control the
      disease in the wild and farmed fish population is yet to be developed.
      Recombinase polymerase amplification (RPA) is a novel isothermal nucleic acid
      amplification technology that does not require any thermal cycling, and lateral
      flow dipstick (LFD) is a rapid, cost-effective, and easy-to-handle assay that
      enables stable detection. RESULTS: In this study, we developed and optimized a
      rapid and sensitive RPA assay combined with an LFD for the detection of T.
      bryosalmonae. The PKD-RPA assay was specific to T. bryosalmonae, as no cross
      reaction or false positive signals were observed with any of the other tested
      DNAs. The developed PKD-RPA assay was ten times more sensitive than an existing
      diagnostic polymerase chain reaction (PCR) assay for this parasite. The estimated
      time to perform PKD-RPA assay is 25 min compared to 4 h for PKD-PCR assay.
      CONCLUSIONS: A novel PKD-RPA assay for the detection of T. bryosalmonae was
      developed. The assay offers considerable advantages including speed, sensitivity,
      specificity and visual detection. Applying the PKD-RPA assay combined with an LFD
      enhances the surveillance and early detection of T. bryosalmonae in salmonids.

PMID- 29642954
TI  - Haemaphysalis cretacea a nymph of a new species of hard tick in Burmese amber.
AB  - The first fossil potentially assignable to the extant hard tick genus
      Haemaphysalis CL Koch (1844) (Ixodida: Ixodidae) is described from the Late
      Cretaceous (ca. 99 Ma) Burmese amber of Myanmar. Haemaphysalis (Alloceraea)
      cretacea sp. nov. is the oldest and only fossil representative of this genus;
      living members of which predominantly feed on mammals. Their typical hosts are
      known since at least the Jurassic and the discovery of a mid-Cretaceous parasite,
      which might have fed on mammals raises again the question of to what extent ticks
      are coupled to their (modern) host groups. An inferred Triassic split of
      Argasidae (soft ticks) into the bird-preferring Argasinae and mammal-preferring
      Ornithodorinae dates to about the time when dinosaurs (later including birds) and
      mammaliaforms as potential hosts were emerging. Ixodidae may have split into
      Prostriata and Metastriata shortly after the end-Permian mass extinction, an
      event which fundamentally altered the terrestrial vertebrate fauna. Prostriata
      (the genus Ixodes) prefer birds and mammals today, and some may have used groups
      like cynodonts in the Triassic. Basal metastriate ticks (e.g. Amblyomma) prefer
      reptiles, but derived metastriates (including Haemaphysalis) again prefer
      mammals. Here, we may be looking at a younger (Cretaceous?) shift associated with
      more recent mammalian radiations.

PMID- 29642953
TI  - Impact of bone marrow mesenchymal stem cell immunomodulation on the osteogenic
      effects of laponite.
AB  - BACKGROUND: With the development of osteoimmunology and bone tissue engineering
      (BTE), it has been recognized that the immunomodulatory properties of bone
      biomaterials have considerable impact in determining their fate after
      implantation. In this regard, the polarization of macrophages secondary to
      biomaterials is postulated to play a crucial role in modulating their
      osteogenesis; thus, strategies that may facilitate this process engender
      increasing levels of attention. Whereas a variety of reports highlight the
      immunomodulation of bone marrow mesenchymal stem cells (BMSCs) in cell therapy or
      their osteogenesis in BTE, few have focused on the effect of BMSCs in promoting
      osteogenesis in BTE through regulating the phenotype of macrophages. Accordingly,
      there is an urgent need to clarify the immunomodulatory properties of agents such
      as laponite (Lap), which is comprised of bioactive silicate nanoplatelets with
      excellent osteogenesis-inducing potential, to enhance their use in BTE. METHODS:
      In the present study, we analyzed the osteoimmunomodulatory properties of Lap
      alone, as well as following the introduction of BMSCs into Lap, to determine
      whether BMSCs could modulate its immunomodulatory properties and promote
      osteogenesis. RESULTS: It was found that the BMSCs reversed the polarization of
      murine-derived macrophage RAW 264.7 cells from M1 as induced by pure Lap to M2
      and promoted osteogenesis. In vivo study confirmed that BMSCs combined with Lap
      initiated a less severe immune response and had an improved effect on bone
      regeneration compared with Lap alone, which corresponded with the in vitro
      evaluation. CONCLUSION: These results suggest that BMSCs could ameliorate the
      inflammation induced by Lap and enhance its bone formation. The immunomodulatory
      characteristics of BMSCs suggest that these might be tailored as a new strategy
      to promote the osteogenic capacity of biomaterials.

PMID- 29642955
TI  - SUCCESSFUL IMPLEMENTATION OF LEAN AS A MANAGERIAL PRINCIPLE IN HEALTH CARE: A
      CONCEPTUAL ANALYSIS FROM SYSTEMATIC LITERATURE REVIEW.
AB  - PURPOSE: The aim of this study was to identify and analyze the characteristics of
      leadership and management associated with a successful Lean thinking adaptation
      in healthcare. DESIGN: A systematic literature review was undertaken using
      electronic databases: PubMed, PubMed Systematic Review, ABI/INFORM, Business
      Source Complete, Emerald, JBI, and Cinahl. Inclusion criteria were: (i) a
      description of Lean management or leadership in health care, (ii) a reference to
      Lean thinking, (iii) a peer-reviewed original research article or a literature
      review, and (iv) a full text article available in English. Among the 1,754 peer
      reviewed articles identified, nine original articles and three systematic reviews
      met the inclusion criteria. Data on informants, methods, and settings were
      extracted and collated. Content analysis was used to conduct a review of the nine
      original studies describing and analyzing the success factors of Lean adaptation.
      The characteristics of leadership and management were analyzed by using the
      concept of a managerial windshield that divides leadership and management into
      four ontological dimensions: activities, style, focus, and purpose, each with
      typical developmental stages of skills and capabilities. The current study has
      some limitations: some papers from the journals not indexed in the searched
      databases may have been overlooked and the literature searches were carried out
      only for a 5-year period. FINDINGS: Considering the results using the windshield
      concept emphasizes the philosophy, principles, and tools of Lean thinking. Lean
      leadership and management factors in health care were mainly conceptualized as
      skills and capabilities such as problem solving, making changes occur,
      empowering, communicating, coaching, supporting, facilitating, being democratic,
      organizational learning, and organizational success, all of which represented
      middle-stage or advanced managerial skills and capabilities. PRACTICAL
      IMPLICATIONS: A conceptual analysis of systematically reviewed studies of Lean
      leadership and management point to certain traits as being typical when adapting
      Lean thinking to health care. The concept of a managerial windshield is useful
      when categorizing and analyzing essential managerial skills and capabilities for
      Lean implementation. Findings are beneficial when learning and educating the
      skills required for Lean transformation in healthcare organizations.

PMID- 29642956
TI  - The reduced genome of Candidatus Kinetoplastibacterium sorsogonicusi, the
      endosymbiont of Kentomonas sorsogonicus (Trypanosomatidae): loss of the haem
      synthesis pathway.
AB  - Trypanosomatids of the genera Angomonas and Strigomonas (subfamily
      Strigomonadinae) have long been known to contain intracellular beta
      proteobacteria, which provide them with many important nutrients such as haem,
      essential amino acids and vitamins. Recently, Kentomonas sorsogonicus, a
      divergent member of Strigomonadinae, has been described. Herein, we characterize
      the genome of its endosymbiont, Candidatus Kinetoplastibacterium sorsogonicusi.
      This genome is completely syntenic with those of other known Ca.
      Kinetoplastibacterium spp., but more reduced in size (~742 kb, compared with 810
      833 kb, respectively). Gene losses are not concentrated in any hot-spots but are
      instead distributed throughout the genome. The most conspicuous loss is that of
      the haem-synthesis pathway. For long, removing haemin from the culture medium has
      been a standard procedure in cultivating trypanosomatids isolated from insects;
      continued growth was considered as an evidence of endosymbiont presence. However,
      we demonstrate that, despite bearing the endosymbiont, K. sorsogonicus cannot
      grow in culture without haem. Thus, the traditional test cannot be taken as a
      reliable criterion for the absence or presence of endosymbionts in trypanosomatid
      flagellates. It remains unclear why the ability to synthesize such an essential
      compound was lost in Ca. K. sorsogonicusi, whereas all other known bacterial
      endosymbionts of trypanosomatids retain them.

PMID- 29642957
TI  - Characterization of mitochondrion-targeted GTPases in Plasmodium falciparum.
AB  - Ribosome assembly is critical for translation and regulating the response to
      cellular events and requires a complex interplay of ribosomal RNA and proteins
      with assembly factors. We investigated putative participants in the biogenesis of
      the reduced organellar ribosomes of Plasmodium falciparum and identified
      homologues of two assembly GTPases - EngA and Obg that were found in
      mitochondria. Both are indispensable in bacteria and P. berghei EngA is among the
      'essential' parasite blood stage proteins identified recently. PfEngA and PfObg1
      interacted with parasite mitoribosomes in vivo. GTP stimulated PfEngA interaction
      with the 50S subunit of Escherichia coli surrogate ribosomes. Although PfObg1
      ribosome interaction was independent of nucleotide binding, GTP hydrolysis by
      PfObg1 was enhanced upon ribosomal association. An additional function for PfObg1
      in mitochondrial DNA transactions was suggested by its specific interaction with
      the parasite mitochondrial genome in vivo. Deletion analysis revealed that the
      positively-charged OBG (spoOB-associated GTP-binding protein) domain mediates DNA
      binding. A role for PfEngA in mitochondrial genotoxic stress response was
      indicated by its over-expression upon methyl methanesulfonate-induced DNA damage.
      PfEngA had lower sensitivity to an E. coli EngA inhibitor suggesting differences
      with bacterial counterparts. Our results show the involvement of two important
      GTPases in P. falciparum mitochondrial function, with the first confirmed
      localization of an EngA homologue in eukaryotic mitochondria.

PMID- 29642958
TI  - Consumption of ultra-processed food and obesity: cross sectional results from the
      Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) cohort (2008-2010).
AB  - OBJECTIVE: To verify if the intake of ultra-processed foods is associated with
      higher BMI and waist circumference (WC) among participants of the Brazilian
      Longitudinal Study of Adult Health (ELSA-Brasil) cohort. DESIGN: Cross-sectional
      analysis of the ELSA-Brasil baseline (2008-2010). Dietary information obtained
      through an FFQ was classified according to characteristics of food processing
      (NOVA) and used to estimate the percentage energy contribution from ultra
      processed foods (i.e. industrial formulations, elaborated from food processing,
      synthetic constituents and food additives) to individuals' total energy intake.
      BMI and WC and their respective cut-off points served as response variables.
      Associations were estimated through linear and multinomial logistic regression
      models, after adjusting for confounders and total energy intake. SETTING: Six
      Brazilian capital cities, 2008-2010. SUBJECTS: Active and retired civil servants,
      aged 35-64 years, from universities and research organizations (n 8977). RESULTS:
      Ultra-processed foods accounted for 22.7 % of total energy intake. After
      adjustments, individuals in the fourth quartile of percentage energy contribution
      from ultra-processed foods presented (beta; 95 % CI) a higher BMI (0.80; CI 0.53,
      1.07 kg/m2) and WC (1.71; 1.02, 2.40 cm), and higher chances (OR; 95 % CI) of
      being overweight (1.31; 1.13, 1.51), obese (1.41; 1.18, 1.69) and having
      significantly increased WC (1.41; 1.20, 1.66), compared with those in the first
      quartile. All associations suggest a dose-response gradient. CONCLUSIONS: Results
      indicate the existence of associations between greater energy contribution from
      ultra-processed foods and higher BMI and WC, which are independent of total
      energy intake. These findings corroborate public policies designed to reduce the
      intake of this type of food.

PMID- 29642959
TI  - Phylogenetic heritability of geographic range size in haematophagous
      ectoparasites: time of divergence and variation among continents.
AB  - To understand existence, patterns and mechanisms behind phylogenetic heritability
      in the geographic range size (GRS) of parasites, we measured phylogenetic signal
      (PS) in the sizes of both regional (within a region) and continental (within a
      continent) geographic ranges of fleas in five regions. We asked whether (a) GRS
      is phylogenetically heritable and (b) the manifestation of PS varies between
      regions. We also asked whether geographic variation in PS reflects the effects of
      the environment's spatiotemporal stability (e.g. glaciation disrupting geographic
      ranges) or is associated with time since divergence (accumulation differences
      among species over time). Support for the former hypothesis would be indicated by
      stronger PS in southern than in northern regions, whereas support for the latter
      hypothesis would be shown by stronger PS in regions with a large proportion of
      species belonging to the derived lineages than in regions with a large proportion
      of species belonging to the basal lineages. We detected significant PS in both
      regional and continental GRSs of fleas from Canada and in continental GRS of
      fleas from Mongolia. No PS was found in the GRS of fleas from Australia and
      Southern Africa. Venezuelan fleas demonstrated significant PS in regional GRS
      only. Local Indicators of Phylogenetic Association detected significant local
      positive autocorrelations of GRS in some clades even in regions in which PS has
      not been detected across the entire phylogeny. This was mainly characteristic of
      younger taxa.

PMID- 29642961
TI  - PREOPERATIVE MAGNETIC RESONANCE IMAGING DIAGNOSTIC FEATURES OF UTERINE
      LEIOMYOSARCOMAS: A SYSTEMATIC REVIEW.
AB  - OBJECTIVES: There are no current established pathognomonic diagnostic features
      for uterine leiomyosarcomas in the pre- or perioperative setting. Recent
      inadvertent upstaging of this rare malignancy during laparoscopic morcellation of
      a presumed fibroid has prompted widespread debate among clinicians regarding the
      safety of current surgical techniques for management of fibroids. This study aims
      to conduct a systematic review investigating significant diagnostic features in
      magnetic resonance imaging (MRI) of uterine leiomyosarcomas. METHODS: A
      comprehensive database search was conducted guided by PRISMA recommendations for
      peer-reviewed publications to November 2017. Parameters available in MRI were
      compared for reliability and accuracy of diagnosis of leiomyosarcomas. A decision
      tree algorithm classifier model was constructed to investigate whether T1 and T2
      MRI signal intensities are useful indicators. RESULTS: Nine eligible studies were
      identified for analysis. There appears to be a significant relationship between
      histopathological type and T1 and T2 intensity signals (p < .05). A decision tree
      model analyzing T1 and T2 signal intensity readings supports this trend, with a
      diagnostic specificity of 77.78 percent for uterine leiomyosarcomas. The apparent
      diffusion coefficient (ADC) values were not observed to have a significant
      relationship with tumor pathology (p = .18). CONCLUSIONS: Various studies have
      investigated pre- and perioperative techniques in differentiating uterine
      leiomyosarcoma from benign fibroids. Given the rarity of the malignancy and lack
      of pathognomonic diagnostic parameters, there is difficulty in establishing
      definitive criteria. A decision tree model is proposed to aid diagnosis based on
      MRI signal intensities.

PMID- 29642962
TI  - Leishmaniasis: current challenges and prospects for elimination with special
      focus on the South Asian region.
AB  - Leishmania donovani, the most virulent species of Leishmania, is found in the
      South Asian region that harbours the majority of visceral leishmaniasis (VL)
      cases in the world. The traditionally accepted relationships between the
      causative species of Leishmania and the resultant disease phenotype have been
      challenged during recent years and have underscored the importance of revisiting
      the previously established taxonomy with revisions to its classification. The
      weak voice of the afflicted with decades of neglect by scientists and policy
      makers have led to the miserably inadequate and slow advancements in product
      development in the fields of diagnostics, chemotherapeutics and vector control
      that continue to hinder the effective management and control of this infection.
      Limitations notwithstanding, the regional drive for the elimination of VL
      initiated over a decade ago that focused on India, Nepal and Bangladesh, the
      three main afflicted countries in the Indian subcontinent is therefore,
      commendable, with the subsequent status reviews and restructuring of strategies
      possibly even more so. However, the renewed efforts would need to be combined
      with plans to combat new challenges in the South-Asian region that includes the
      emergence of atypical parasite variants, in order to realistically achieve the
      set goal of regional elimination of VL.

PMID- 29642963
TI  - Nanoencapsulation of benznidazole in calcium carbonate increases its selectivity
      to Trypanosoma cruzi.
AB  - Chagas disease is a public health problem, affecting about 7 million people
      worldwide. Benznidazole (BZN) is the main treatment option, but it has limited
      effectiveness and can cause severe adverse effects. Drug delivery through
      nanoparticles has attracted the interest of the scientific community aiming to
      improve therapeutic options. The aim of this study was to evaluate the
      cytotoxicity of benznidazole-loaded calcium carbonate nanoparticles (BZN@CaCO3)
      on Trypanosoma cruzi strain Y. It was observed that BZN@CaCO3 was able to reduce
      the viability of epimastigote, trypomastigote and amastigote forms of T. cruzi
      with greater potency when compared with BZN. The amount of BZN necessary to
      obtain the same effect was up to 25 times smaller when loaded with CaCO3
      nanoparticles. Also, it was observed that BZN@CaCO3 enhanced the selectivity
      index. Furthermore, the cell-death mechanism induced by both BZN and BZN@CaCO3
      was evaluated, indicating that both substances caused necrosis and changed
      mitochondrial membrane potential.

PMID- 29642964
TI  - Strengthening primary health care through primary care and public health
      collaboration: the influence of intrapersonal and interpersonal factors.
AB  - : AimThe aim of this paper is to examine Canadian key informants' perceptions of
      intrapersonal (within an individual) and interpersonal (among individuals)
      factors that influence successful primary care and public health collaboration.
      BACKGROUND: Primary health care systems can be strengthened by building stronger
      collaborations between primary care and public health. Although there is
      literature that explores interpersonal factors that can influence successful
      inter-organizational collaborations, a few of them have specifically explored
      primary care and public health collaboration. Furthermore, no papers were found
      that considered factors at the intrapersonal level. This paper aims to explore
      these gaps in a Canadian context. METHODS: This interpretative descriptive study
      involved key informants (service providers, managers, directors, and policy
      makers) who participated in one h telephone interviews to explore their
      perceptions of influences on successful primary care and public health
      collaboration. Transcripts were analyzed using NVivo 9.FindingsA total of 74
      participants [from the provinces of British Columbia (n=20); Ontario (n=19); Nova
      Scotia (n=21), and representatives from other provinces or national organizations
      (n=14)] participated. Five interpersonal factors were found that influenced
      public health and primary care collaborations including: (1) trusting and
      inclusive relationships; (2) shared values, beliefs and attitudes; (3) role
      clarity; (4) effective communication; and (5) decision processes. There were two
      influencing factors found at the intrapersonal level: (1) personal qualities,
      skills and knowledge; and (2) personal values, beliefs, and attitudes. A few
      differences were found across the three core provinces involved. There were
      several complex interactions identified among all inter and intra personal
      influencing factors: One key factor - effective communication - interacted with
      all of them. Results support and extend our understanding of what influences
      successful primary care and public health collaboration at these levels and are
      important considerations in building and sustaining primary care and public
      health collaborations.

PMID- 29642960
TI  - CYP51 as drug targets for fungi and protozoan parasites: past, present and
      future.
AB  - The efficiency of treatment of human infections with the unicellular eukaryotic
      pathogens such as fungi and protozoa remains deeply unsatisfactory. For example,
      the mortality rates from nosocomial fungemia in critically ill, immunosuppressed
      or post-cancer patients often exceed 50%. A set of six systemic clinical azoles
      [sterol 14alpha-demethylase (CYP51) inhibitors] represents the first-line
      antifungal treatment. All these drugs were discovered empirically, by monitoring
      their effects on fungal cell growth, though it had been proven that they kill
      fungal cells by blocking the biosynthesis of ergosterol in fungi at the stage of
      14alpha-demethylation of the sterol nucleus. This review briefs the history of
      antifungal azoles, outlines the situation with the current clinical azole-based
      drugs, describes the attempts of their repurposing for treatment of human
      infections with the protozoan parasites that, similar to fungi, also produce
      endogenous sterols, and discusses the most recently acquired knowledge on the
      CYP51 structure/function and inhibition. It is our belief that this information
      should be helpful in shifting from the traditional phenotypic screening to the
      actual target-driven drug discovery paradigm, which will rationalize and
      substantially accelerate the development of new, more efficient and pathogen
      oriented CYP51 inhibitors.

PMID- 29642965
TI  - Host-symbiont-pathogen interactions in blood-feeding parasites: nutrition, immune
      cross-talk and gene exchange.
AB  - Animals are common hosts of mutualistic, commensal and pathogenic microorganisms.
      Blood-feeding parasites feed on a diet that is nutritionally unbalanced and thus
      often rely on symbionts to supplement essential nutrients. However, they are also
      of medical importance as they can be infected by pathogens such as bacteria,
      protists or viruses that take advantage of the blood-feeding nutritional strategy
      for own transmission. Since blood-feeding evolved multiple times independently in
      diverse animals, it showcases a gradient of host-microbe interactions. While some
      parasitic lineages are possibly asymbiotic and manage to supplement their diet
      from other food sources, other lineages are either loosely associated with
      extracellular gut symbionts or harbour intracellular obligate symbionts that are
      essential for the host development and reproduction. What is perhaps even more
      diverse are the pathogenic lineages that infect blood-feeding parasites. This
      microbial diversity not only puts the host into a complicated situation -
      distinguishing between microorganisms that can greatly decrease or increase its
      fitness - but also increases opportunity for horizontal gene transfer to occur in
      this environment. In this review, I first introduce this diversity of mutualistic
      and pathogenic microorganisms associated with blood-feeding animals and then
      focus on patterns in their interactions, particularly nutrition, immune cross
      talk and gene exchange.

PMID- 29642966
TI  - Identifying sociodemographic, programmatic and dietary drivers of anaemia
      reduction in pregnant Indian women over 10 years.
AB  - OBJECTIVE: Anaemia is a major contributor to the global disease burden and half
      of pregnant women in India were anaemic in 2016. The aetiology of anaemia is
      complex, yet anaemia determinants are frequently examined in isolation. We sought
      to explore how shifts in sociodemographic (wealth, age at pregnancy, education,
      open defecation, cooking fuel type, household size), programmatic (iron-folic
      acid tablet consumption, antenatal care visits) and dietary factors (intake of
      Fe, folic acid, vitamin B12, phytate) predicted changes in anaemia prevalence.
      DESIGN: Nutrient levels for eighty-eight food items were multiplied by household
      consumption of these foods to estimate household-level nutrient supply. A
      synthetic panel data set was created from two rounds of the District Level
      Household and Facility Survey (2002-04 and 2012-13) and Household Consumer
      Expenditures Survey (2004-05 and 2011-12). Ordinary least-squares multivariate
      regression models were used. SETTING: Districts (n 446) spanning north, north
      east, central and south India. SUBJECTS: Pregnant women aged 15-49 years (n 17
      138). RESULTS: In the model accounting for both non-dietary and dietary factors,
      increased age at pregnancy (P<0.001), reduced village-level open defecation
      (P=0.001), consuming more Fe (P<0.001) and folic acid (P=0.018) and less phytate
      (P=0.002), and urbanization (P=0.015) were associated with anaemia reductions. A
      10 mg increase in daily household Fe supply from 2012 levels was associated with
      a 10 % reduction in anaemia. CONCLUSIONS: Public health interventions to combat
      anaemia in pregnant women should use a holistic approach, including promotion of
      delayed marriage, construction and use of toilets, and measures that facilitate
      adoption of nutrient-rich diets.

PMID- 29642967
TI  - Heritability of Cold and Heat Patterns: A Twin Study.
AB  - In traditional East Asian medicine, cold-heat patterns have been widely used in
      the diagnosis and treatment of patients suffering from various diseases. The
      present study aimed to estimate the heritability of cold-heat patterns. Trained
      interviewers administered a cold-heat pattern questionnaire to 1,753 twins (mean
      age = 19.1 +/- 3.1 years) recruited throughout South Korea. Correlations for the
      cold pattern (CP) were 0.42 (95% CI [0.28, 0.54]) for monozygotic (MZ) males,
      0.16 (95% CI [-0.08, 0.39]) for dizygotic (DZ) males, 0.40 (95% CI [0.30, 0.49])
      for MZ females, 0.30 (95% CI [0.12, 0.45]) for DZ females, and 0.07 (95% CI [
      0.11, 0.25]) for opposite-sex DZ twins. The corresponding twin correlations for
      the heat pattern (HP) were 0.38 (95% CI [0.24, 0.51]), -0.22 (95% CI [-0.43,
      0.02]), 0.34 (95% CI [0.24, 0.43]), 0.21 (95% CI [0.03, 0.37]), and 0.08 (95% CI
      [-0.10, 0.26]), respectively. These patterns of twin correlations suggested
      significant genetic effects on the HP and the CP. Model-fitting analysis revealed
      that heritability estimates in both sexes were 40% (95% CI [38, 42]) for the CP
      and 33% (95% CI [25, 42]) for the HP, with the remaining variances attributable
      to unique environmental variances. These estimates did not vary significantly
      with age during adolescence and young adulthood.

PMID- 29642968
TI  - Review: Historical and futuristic developments in bovine semen technology.
AB  - Up to the 18th century, the prevailing view of reproduction, or 'generation' as
      it was referred to, was that organisms develop from miniatures of themselves,
      termed preformation. The alternative theory, epigenesis, proposed that the
      structure of an animal emerges gradually from a relatively formless egg. The
      teachings of the Ancient Greeks who argued either that both sexes each
      contributed 'semen' to form the embryo, or held a more male-centred view that the
      female merely provided fertile ground for the male seed to grow, dominated
      thinking until the 17th century, when the combined work of numerous scholars led
      to the theory that all female organisms, including humans, produced eggs. The
      sequence of events leading to the commercial use of artificial insemination (AI)
      date back to the discovery of sperm in 1678, although it took almost 100 years to
      demonstrate that sperm were the agents of fertilisation and a further 100 years
      for the detailed events associated with fertilisation to be elucidated. The first
      successful AI, carried out in the dog, dates back to 1780 while it was not until
      the early to mid-1900s that practical methods for AI were described in Russia.
      Inspired by the Russian success, the first AI cooperative was established in
      Denmark in 1936 and later in the United States in 1938. The next major advances
      involved development of semen extenders, addition of antibiotics to semen, and
      the discovery in 1949 that glycerol protected sperm during cryopreservation.
      Almost four decades later, the flow cytometric separation of X- and Y-bearing
      sperm opened a new chapter in the application of AI for cattle breeding. As we
      look forward today, developments in imaging sperm and breakthroughs in gene
      editing and stem cell technology are opening up new possibilities to manipulate
      reproduction in a way never thought possible by the pioneers of the past. This
      review highlights some of the main milestones and individuals in the history of
      sperm biology and the development of technologies associated with AI in cattle.

PMID- 29642969
TI  - Gametogony of Eimeria macusaniensis Guerrero, Hernandez, Bazalar and Alva, 1971
      in llama (Lama glama).
AB  - Camelids (llama, alpaca, vicunas, guanacos) are important for the economy of
      South America and Eimeria infections are an important cause of mortality in
      camelids. Of the six species of Eimeria in camelids, Eimeria macusaniensis,
      considered the most pathogenic, is distinctive; its oocysts are the largest among
      all Eimeria species in animals, its prepatent period is more than 1 month, and
      its oocysts have been found in mummies from prehistoric times. Although, E.
      macusaniensis gametogonic stages are found associated with enteritis in naturally
      infected camelids, the schizogonic stages are unknown and clinical disease has
      been reported in some camelids with no oocysts in feces. Described herein are
      morphological details of gametogonic development and oocyst formation of E.
      macusaniensis in a naturally infected llama (Lama lama), solely infected with
      this parasite. Microgamonts, macrogamonts and oocysts were located in large (up
      to 300 um diameter) parasitophorous vacuoles of enterocytes in the ileum.
      Schizonts were not found. Review of previous reports suggests that multinucleated
      microgamonts have been mistaken for schizonts. Gametogonic development described
      in the present study can serve as a guide for differential diagnosis of Eimeria
      species in the histological sections of intestines.

PMID- 29642971
TI  - Pragmatic implementation studies to improve nutrition practices and policies:
      childcare during the first 1000 days as a contributor to long-term health.

PMID- 29642970
TI  - Work aggravated asthma in Great Britain: a cross-sectional postal survey.
AB  - OBJECTIVE: Work aggravated asthma (WAA), asthma made worse by but not caused by
      workplace exposures, can have a negative impact on personal, social, financial
      and societal costs. There is limited data on prevalence levels of WAA in Great
      Britain (GB). The objective of this study was to estimate the prevalence of WAA
      in GB, and to assess its potential causes.Materials and methodsA cross-sectional
      postal questionnaire study was carried out. A total of 1620 questionnaires were
      sent to three populations of adults with asthma. The questionnaire recorded;
      demographic details, current job, self-reported health status, presence of asthma
      and respiratory symptoms, duration and severity of symptoms and medication
      requirements. Questions relating to work environment and employers' actions were
      included, and each participant completed an assessment of health-related quality
      of life using the EuroQol Research Foundation EQ-5D. RESULTS: There were 207
      completed questionnaires; response rates were 6% primary care, 45% secondary care
      and 71% Asthma UK. This represented a 13% overall response rate. Self-reported
      prevalence of WAA was 33% (95% CI 24.4-41.6%). In all, 19% of workers had changed
      their job because of breathing problems. Workers with WAA reported higher levels
      of work-related stress. Quality of life using the EQ-5D utility index was lower
      in those with WAA. CONCLUSION: WAA is a common problem in asthmatics in GB. This
      result is in keeping with international prevalence rates. Further research could
      assist the understanding of the most significant aggravants to asthma at work and
      help define appropriate interventions by workplaces.

PMID- 29642972
TI  - The Association of Intrapair Birth-Weight Differences With Internalizing and
      Externalizing Behavior Problems.
AB  - Problem behaviors are of increasing public health concern. Twin studies have
      revealed substantial genetic and environmental influences on children's behavior,
      and examining birth-weight difference could allow the identification of the
      specific contribution of multiple non-shared prenatal environmental factors. The
      Twins and Multiple Births Association Heritability Study, a UK, volunteer-based
      study, recruited mothers of twins aged 18 months to 5 years; 960 twins (480
      pairs) were included in the analysis. Twins' mothers answered questions relative
      to their pregnancy and their twins' characteristics, and completed the Child
      Behavior Checklist (CBCL) 11/2-5. The association between the absolute birth
      weight difference and each CBCL scale's score difference was analyzed by means of
      multiple linear regressions. Expected mean CBCL score differences were
      calculated. In monozygotic (MZ) twins, statistically and clinically significant
      associations were found between intrapair birth-weight difference and difference
      in total problems, internalizing problems, and emotional reactiveness. No
      significant results were observed neither in dizygotic (DZ) twins when analyzed
      as a separate group nor in MZ and DZ twins combined. The results of the present
      study suggest that with increasing the absolute birth-weight difference, the
      intrapair difference in total problems, internalizing behaviors and emotionality
      increases, with smaller twins being at major risk for later behavior problems.
      Moreover, these results suggest a causal association between birth weight and
      behavior development.

PMID- 29642975
TI  - Management of a Complex Case of a Bronchopleural Fistula.

PMID- 29642973
TI  - Enhancing health literacy through co-design: development of culturally
      appropriate materials on genetic risk and customary consanguineous marriage.
AB  - : AimTo develop a simple health literacy intervention aimed at supporting
      informed reproductive choice among members of UK communities practising customary
      consanguineous marriage. BACKGROUND: The contribution of 'health literacy' to
      reducing health inequalities and improving primary health-care efficiency is
      increasingly recognised. Enhancing genetic literacy has received particular
      attention recently. Consanguineous marriage is customarily practised among some
      UK minority ethnic communities and carries some increased risk of recessive
      genetic disorders among offspring compared with unions among unrelated partners.
      The need to enhance genetic literacy on this issue has been highlighted, but no
      national response has ensued. Instead, a range of undocumented local responses
      are emerging. Important knowledge gaps remain regarding how the development and
      implementation of culturally appropriate, effective and sustainable responses can
      be achieved. METHODS: Our co-design approach involved active participation by
      local people. Initial insight generation employed six focus group discussions and
      14 individual interviews to describe current understandings and information
      needs. A total of 11 personas (heuristic narrative portraits of community
      'segments') resulted; four participatory workshops provided further understanding
      of: preferred information channels; feasible information conveyance; and
      responses to existing materials. Prototype information resources were then
      developed and feedback gathered via two workshops. Following further refinement,
      final feedback from health-care professionals and community members ensured
      accuracy and appropriateness.FindingsThe project demonstrated the utility of co
      design for addressing an issue often considered complex and sensitive. With
      careful planning and orchestration, active participation by diverse community
      members was achieved. Key learning included: the importance of establishing
      trusting and respectful relationships; responding to diversity within the
      community; and engendering a creative and enjoyable experience. The resultant
      materials were heavily shaped by local involvement. Evaluative work is now needed
      to assess impacts on knowledge and service uptake. Longer term sustainability
      will depend on whether innovative community-level work is accompanied by broader
      strategy including investment in services and professional development.

PMID- 29642976
TI  - Thoracic Impalement by a Steel Reinforcing Bar.

PMID- 29642977
TI  - Curative Resection for Hilar Cholangiocarcinoma: Single-Center Experience with
      Long-Term Follow-Up.

PMID- 29642978
TI  - Preprocedural Fasting: Is it Time to Change Practice?

PMID- 29642980
TI  - Suprapubic Midline Extraperitoneal Approach for Widespread Retroperitoneal
      Abscess Originating from Anorectal Abscess.

PMID- 29642979
TI  - Creatinine Kinase and Stimulant Abuse in Trauma.

PMID- 29642981
TI  - Thoracic Endovascular Repair and Omental Flap Revision of Aortopulmonary Fistula
      Involving Aortic Pseudoaneurysm.

PMID- 29642984
TI  - The Effect of Regional Anesthesia on Oncologic Outcomes after Resection of
      Colorectal Hepatic Metastases.

PMID- 29642985
TI  - Retained Capsule Endoscopy in a Patient with a Meckel Diverticulum Previously
      Treated by Endovascular Embolization.

PMID- 29642986
TI  - Academic versus Clinical Productivity of (Elite) United States Transplant
      Surgeons: Who Publishes More and Who Operates More.

PMID- 29642988
TI  - Status of lymphatic filariasis with progression of age and gender & eradication
      strategies: A survey among residents of Hardoi district of Uttar Pradesh, an
      endemic region of North India.
AB  - Lymphatic filariasis (LF) is a chronic and debilitating disease that affects
      people in tropical and sub-tropical areas of Asia, Africa, and Western Pacific.
      It is one of the leading community health problems in some of the endemic
      districts in India including Hardoi district of Uttar Pradesh. The disease is
      caused by the parasites Wuchereria bancrofti (W. bancrofti), Brugia malayi (B.
      malayi) and Brugia timori (B. timori), transmitted by the vector Culex, Anopheles
      and other mosquitoes. This cross-sectional survey study was carried out in rural
      areas, where its inhabitants vary in socio-economic status, from low to middle
      income class. 12 villages of Hardoi district, Uttar Pradesh, India were included.
      The aim was to see the impact of age and gender on various clinical forms of LF
      and in estimating its economic and social implications. 260 LF affected people in
      different parts of Hardoi district were surveyed. The results revealed that the
      Mass Drug Administration (MDA) coverage reached more than 90%. The overall
      Microfilaria rate had been reduced, however the prevalence of elephantiasis
      increased with the progression of age and was found to be highest among people of
      >70 years of age, regardless of their gender.

PMID- 29642989
TI  - Cardiogenic Causes of Fever.
AB  - BACKGROUND: Persistent fever of unknown cause is only rarely of cardiac origin,
      but heart disease must be considered in the differential diagnosis. Aside from
      endocarditis, pericarditis and various other conditions may be responsible.
      METHODS: This review is based on pertinent articles retrieved by a selective
      search in PubMed and Google Scholar employing the term "fever" in combination
      with "myocardial infarction," "pericarditis," "endocarditis," and "postcardiac
      injury," with additional consideration of current cardiological guidelines.
      RESULTS: Endocarditis is associated with fever in 90% of cases, but 25-50% of
      patients also develop high body temperatures after acute myocardial infarction.
      In pericarditis, a temperature above 38 degrees C indicates a poorer prognosis;
      if accompanied by other warning signs, it is an indication for hospitalization
      and pericardiocentesis. Fever can arise after cardiac surgical procedures as a
      manifestation of post - cardiotomy syndrome, a special type of perimyocarditis.
      There may be a latency period of up to 3 months. CONCLUSION: Fever can have both
      infectious and non-infectious cardiac causes. Its interpretation depends on the
      clinical context. The evidence base for treatment is sparse, and controlled
      trials are needed.

PMID- 29642991
TI  - No Panacea in Sight.

PMID- 29642992
TI  - In Reply.

PMID- 29642990
TI  - Oral Interventions for Obstructive Sleep Apnea.
AB  - BACKGROUND: The effectiveness of intraoral appliances (IOA), maxillary expansion
      (ME), and maxillomandibular advancement (MMA) in the treatment of children and
      adults with obstructive sleep apnea (OSA) has not yet been adequately assessed.
      METHODS: An umbrella review was performed based on established guidelines for
      evidence-based medicine. Data synthesis was performed only from randomized
      controlled trials with Paule-Mandel random-effects meta-analyses / meta
      regressions using mean differences (MDs) and 95% confidence intervals (CIs) and
      was followed by the qualitative evaluation of the meta-evidence. RESULTS: 29
      systematic reviews were included, 7 of which provided quantitative data. IOA were
      effective in improving apnea hypopnea index (AHI) compared to both, placebo
      appliances (12 trials; 525 patients; MD = -11.70; 95% CI: [-15.38; -8.01];
      p<0.001) and no treatment (1 trial; 24 patients; MD = -14.30; [-21.59; -7.01];
      p<0.001). Only the former comparison was supported by robust meta-evidence.
      Effectiveness of IOA as measured by the Epworth Sleepiness Scale, on the other
      hand, was not supported by robust meta-evidence. No randomized or prospective
      controlled trials were found on the effectiveness of ME (conventional or
      surgically assisted) and MMA. CONCLUSION: Intraoral appliances are effective in
      reducing AHI and their use is substantiated by robust evidence. There is no
      evidence from high-quality research to support treatment with ME (conventional or
      surgically assisted) or MMA in patients with OSA.

PMID- 29642993
TI  - A 21-Year-Old Man With Coronary Artery Dissection After Blunt Trauma to the
      Chest.

PMID- 29642994
TI  - Questions upon Questions.

PMID- 29642995
TI  - In Reply.

PMID- 29642996
TI  - Retraction: A mathematical model explains saturating axon guidance responses to
      molecular gradients.

PMID- 29642997
TI  - Gender differences in symptom presentation of ST-elevation myocardial infarction 
      An observational multicenter survey study.
AB  - BACKGROUND: Symptom presentation has been sparsely studied from a gender
      perspective restricting the inclusion to ST elevation myocardial infarction
      (STEMI) patients. Correct symptom recognition is vital in order to promptly seek
      care in STEMI where fast reperfusion therapy is of utmost importance. Female
      gender has been found associated with atypical presentation in studies on mixed
      MI populations but it is unclear whether this is valid also in STEMI. OBJECTIVES:
      We assessed whether there are gender differences in symptoms and interpretation
      of these in STEMI, and if this is attributable to sociodemographic and clinical
      factors. METHODS: SymTime was a multicenter observational study including a
      validated questionnaire and data from medical records. Eligible STEMI patients (n
      = 532) were enrolled within 24 h after admittance at five Swedish hospitals.
      RESULTS: Women were older, more often single and had lower educational level.
      Chest pain was less prevalent in women (74 vs 93%, p < 0.001), whereas shoulder
      (33 vs 15%, p < 0.001), throat/neck (34 vs 18%, p < 0.001), back pain (29 versus
      12%, p < 0.001) and nausea (49 vs 29%, p < 0.001) were more prevalent. Women less
      often interpreted their symptoms as of cardiac origin (60 vs 69%, p = 0.04).
      Female gender was the strongest independent predictor of non-chest pain
      presentation, odds ratio 5.29, 95% confidence interval 2.85-9.80. CONCLUSIONS: A
      striking gender difference in STEMI symptoms was found. As women significantly
      misinterpreted their symptoms more often, it is vital when informing about MI to
      the society or to high risk individuals, to highlight also other symptoms than
      just chest pain.

PMID- 29642998
TI  - Burden of arrhythmia in recreational marijuana users.
AB  - Marijuana or Cannabis is extensively used as a recreational substance globally.
      Case reports have reported cardiac arrhythmias immediately following recreational
      marijuana use. However, the burden of arrhythmias in hospitalized marijuana users
      have not been evaluated through prospective or cross-sectional studies.
      Therefore, we planned to measure temporal trends of the frequency of arrhythmias
      in hospitalized marijuana users using National Inpatient Sample (NIS) database in
      the United States.

PMID- 29642999
TI  - Treatment of stress urinary incontinence after prostatectomy with the adjustable
      transobturator male system (ATOMS(r)) with preattached scrotal port.
AB  - INTRODUCTION: Stress urinary incontinence (SUI) is a significant sequela of
      prostate cancer surgery. In this article, we present the surgical technique and
      safety and efficacy of the adjustable transobturator male system (ATOMS(r)) with
      preattached scrotal port. MATERIAL AND METHOD: An open prospective study was
      conducted at a university hospital with the main objective of changing the
      baseline condition after adjustment in the daily pad count and their wet weight
      (pad test). The secondary objectives were the quality-of-life assessment
      (International Consultation on Incontinence Questionnaire-Short Form [ICIQ-SF]
      and Incontinence Impact Questionnaire-7 [IIQ-7], baseline and after the
      adjustment), patient-perceived results (Patient Global Index [PGI] and Global
      Response Assessment [GRA] at 1 year) and assessment of complications according to
      Clavien-Dindo. The numerical values are expressed in median +/- IQR. RESULTS: We
      analysed 60 consecutive patients with a follow-up of 21+/-22 months. The baseline
      pad-test was 465+/-450mL, and the pad-count was 5+3 pads/day. The baseline SUI
      was mild (11.6% of patients), moderate (25%) and severe (63.3%). The operative
      time was 60+/-25min, the hospital stay was 1+/-0 days, and the visual analogue
      scale of pain on day 1 after surgery was 0+/-1. The total filling was 16.5+/-7mL,
      and the number of refillings was 1+/-2. The pad-test and pad-count after the
      adjustment were 0+/-20mL and 0+/-1, respectively (both p<.0001 compared with
      baseline). SUI disappeared (81.7%) or remained mild (11.7%), moderate (5%) or
      severe (1.6%). We observed a reduction in the ICIQ-SF (p<.0001) and IIQ-7 scores
      (p=.0003). Both continence (p=.002) and satisfaction (p=.03) were lower in the
      irradiated patients. Complications occurred in 11 cases (18.6%), 8 (13.5%) of
      which were grade I and 3 (5.1%) of which were grade 3. The treatment satisfaction
      rate was 91.7%, and the patient-perceived overall improvement at 1 year was
      highly pronounced (PGI-I score, 1+/-1; GRA, 6+/-1). CONCLUSIONS: SUI treatment of
      men using third-generation ATOMS(r) is safe and effective in the short-term, even
      in patients with severe SUI. The rate of dry patients after the adjustment
      exceeded 80%, and the satisfaction rates exceeded 90%. The patients assessed this
      treatment highly positively.

PMID- 29643000
TI  - The Therapeutic Challenge of Rare Diseases.

PMID- 29643001
TI  - Immune-cell BDNF expression in treatment-naive relapsing-remitting multiple
      sclerosis patients and following one year of immunomodulation therapy.
AB  - Although neurons are the main source of neurotrophins in the healthy brain,
      neurotrophins can also be expressed in the immune system. We have previously
      shown that in relapsing-remitting multiple sclerosis (RRMS) lower immune-cell
      neurotrophin levels are associated with brain atrophy and cognitive impairment.
      The aim of the present study was to assess if immune-cell neurotrophin expression
      is impaired in MS as compared with the healthy controls, and to describe if these
      levels change in treatment-naive RRMS patients, following one year of
      immunomodulation. Fifty treatment-naive RRMS patients were assessed at baseline
      and after one year of immunomodulation (beta-interferons/glatiramer acetate). The
      control group included 39 healthy subjects matched according to age and gender.
      Peripheral blood mononuclear cells (PBMCs) were isolated from heparinized blood
      using Ficoll-Histopaque gradient. The levels of brain-derived-neurotrophic-factor
      (BDNF), beta-nerve-growth-factor (beta-NGF), neurotrophin-3 (NT-3) and
      neurotrophin-4/5 (NT-4/5) were measured in PBMC lysates with ELISA. BDNF levels
      were significantly lower in MS than in the healthy controls (median 613 vs.
      1657pg/mg protein, p<0.001). After one year of immunomodulation, BDNF expression
      did not change significantly (p=0.06) on the group level. In 70% of patients
      there was no increase in BDNF level, and in 30% it increased. We observed no
      differences between treatment groups. Other neurotrophins were detected in a
      minority of MS samples (as opposed to the controls). To conclude, we have shown
      that immune-cell production of neurotrophins is impaired in MS patients. In our
      MS cohort standard immunomodulation failed to restore normal BDNF levels in PBMCs
      within one year of therapy.

PMID- 29643002
TI  - 3D printing of a lithium-calcium-silicate crystal bioscaffold with dual
      bioactivities for osteochondral interface reconstruction.
AB  - It is difficult to achieve self-healing outcoming for the osteochondral defects
      caused by degenerative diseases. The simultaneous regeneration of both cartilage
      and subchondral bone tissues is an effective therapeutic strategy for
      osteochondral defects. However, it is challenging to design a single type of
      bioscaffold with suitable ionic components and beneficial osteo/chondral
      stimulation ability for regeneration of osteochondral defects. In this study, we
      successfully synthesized a pure-phase lithium calcium silicate (Li2Ca4Si4O13,
      L2C4S4) bioceramic by a sol-gel method, and further prepared L2C4S4 scaffolds by
      using a 3D-printing method. The compressive strength of L2C4S4 scaffolds could be
      well controlled in the range of 15-40 MPa when pore size varied from 170 to 400
      MUm. L2C4S4 scaffolds have been demonstrated to possess controlled
      biodegradability and good apatite-mineralization ability. At a certain
      concentration range, the ionic products from L2C4S4 significantly stimulated the
      proliferation and maturation of chondrocytes, as well as promoted the osteogenic
      differentiation of rBMSCs. L2C4S4 scaffolds simultaneously promoted the
      regeneration of both cartilage and subchondral bone as compared to pure beta-TCP
      scaffolds in rabbit osteochondral defects. These findings suggest that 3D-printed
      L2C4S4 scaffolds with such specific ionic combination, high mechanical strength
      and good degradability as well as dual bioactivities, represent a promising
      biomaterial for osteochondral interface reconstruction.

PMID- 29643003
TI  - A review of the surface features and properties, surfactant adsorption and
      floatability of four key minerals of diasporic bauxite resources.
AB  - Diasporic bauxite represents one of the major aluminum resources. Its upgrading
      for further processing involves a separation of diaspore (the valuable mineral)
      from aluminosilicates (the gangue minerals) such as kaolinite, illite, and
      pyrophyllite. Flotation is one of the most effective ways to realize the
      upgrading. Since flotation is a physicochemical process based on the difference
      in the surface hydrophobicity of different components, determining the adsorption
      characteristics of various flotation surfactants on the mineral surfaces is
      critical. The surfactant adsorption properties of the minerals, in turn, are
      controlled by the surface chemistry of the minerals, while the latter is related
      to the mineral crystal structures. In this paper, we first discuss the crystal
      structures of the four key minerals of diaspore, kaolinite, illite, and
      pyrophyllite as well as the broken bonds on their exposed surfaces after
      grinding. Next, we summarize the surface chemistry properties such as surface
      wettability and surface electrical properties of the four minerals, and the
      differences in these properties are explained from the perspective of mineral
      crystal structures. Then we review the adsorption mechanism and adsorption
      characteristics of surfactants such as collectors (cationic, anionic, and mixed
      surfactants), depressants (inorganic and organic), dispersants, and flocculants
      on these mineral surfaces. The separation of diaspore and aluminosilicates by
      direct flotation and reverse flotation are reviewed, and the collecting
      properties of different types of collectors are compared. Furthermore, the
      abnormal behavior of the cationic flotation of kaolinite is also explained in
      this section. This review provides a strong theoretical support for the
      optimization of the upgrading of diaspore bauxite ore by flotation and the early
      industrialization of the reverse flotation process.

PMID- 29643004
TI  - Association between Mediterranean diet and hand grip strength in older adult
      women.
AB  - BACKGROUND & AIMS: Mediterranean Diet (MD) is an eating pattern associated with
      multiple healthy benefits, including the conservation of skeletal muscle. Frailty
      is a major geriatric syndrome characterized by low muscle strength. The Hand Grip
      Strength (HGS) is the most frequently used indicator of muscle functional
      capacity for clinical purposes. The association between the adherence to the MD
      and HGS in elderly has not yet fully investigated. The goal of this study was to
      examine the association between the adherence to the MD and HGS in a not
      hospitalized elderly who participated in the project PERsonalised ict Supported
      Services for Independent Living and Active Ageing (PERSSILAA). METHODS: Eighty
      four elderly women were consecutively enrolled (aged 60-85 years) in this cross
      sectional observational study. Anthropometric measures were evaluated. A
      validated 14-item questionnaire PREDIMED (PREvencion con DIeta MEDiterranea) was
      used for the assessment of adherence to the MD. Dietary data were collected by a
      7-day food records. Muscle strength was measured by HGS using a grip strength
      dynamometer (KERN & SOHN GmbH). RESULTS: The majority of participants were
      overweight (46.4%). An average adherence to the MD was found in 52.4% of
      participants, while the minority of them showed a low adherence (21.4%). HGS >
      cut-point of 20 kg were found in 43 subjects (51.2%). According to the adherence
      to MD, 39% participants with HGS values higher than cut-point presented a high
      adherence score compared with 14% of those with lower values of HGS (p = 0.018).
      The participants with HGS > cut-point presented significantly higher PREDIMED
      score than those with HGS < cut-point (p < 0.001). Based on ROC curves, the most
      sensitive and specific cut-point for the PREDIMED score to predict HGS categories
      was >=8. No evident correlations were observed between HGS and age, while HGS was
      negatively correlated with hip circumference (r = -0.233, p = 0.033) and BMI (r =
      -0.219, p = 0.045), and positively correlated with PREDIMED score (r = 0.598, p <
      0.001). At binomial logistic regression analysis almost all 14-items of PREDIMED
      questionnaire were significantly associated with HGS adjusted for BMI. At
      multinomial logistic regression analysis to assess the association of the three
      classes of adherence to the MD with the HGS, after adjusting for BMI the lowest
      adherence to MD was associated with the lowest Odds Ratio of HGS (p < 0.001).
      CONCLUSIONS: This study evidenced a positive association between the adherence to
      the MD and muscle strength in a sample of active elderly women, stratified
      according to the HGS > cut-point of 20 kg. Our study highlights the usefulness of
      the developing health services to detect and prevent age-associated decline in
      physical performance in elderly subjects by addressing nutritional and physical
      intervention.

PMID- 29643005
TI  - A case report of orbital Langerhans cell histiocytosis presenting as a orbital
      cellulitis.
AB  - CLINICAL CASE: A 10-year-old girl was seen with a 3-week history of right upper
      lid swelling and with no other symptoms or fever. There was no recent history of
      sinusitis, trauma, or previous infection involving the periorbital area, or
      response to oral antibiotic treatment. Orbital computed tomography showed a
      lesion involving the upper margin of the orbit, and bone destruction at the
      orbital roof. Biopsy performed revealed the presence of Langerhans cell
      Histiocytosis. The lesion was surgically debulked and corticosteroids were used
      intra-operatively. The lesion responded to treatment. DISCUSSION: The orbital
      involvement of Langerhans cell histiocytosis, despite its low incidence, should
      be considered in the examination of acute peri-orbital swelling. It usually
      presents as an osteolytic lesion, and it is confirmed with a histological
      examination and immunohistochemical techniques for CD1a and S100. An
      interdisciplinary approach is recommended to rule out multifocal or multisystemic
      diseases, as well as to develop an appropriate treatment strategy.

PMID- 29643006
TI  - Cerebellar degeneration and progressive ataxia associated with HIV-virus
      infection.
AB  - INTRODUCTION: The spectrum of neurologic disorders associated with HIV infection
      is very broad, resulting from direct virus invasion, opportunistic infections,
      malignancies and toxic effects of drugs. METHODS: Among a large cohort of ataxia
      patients (N = 1050) evaluated between 2008 and 2017, we detected four patients
      with HIV-infection who developed a pure progressive cerebellar ataxia syndrome
      combined with cerebellar atrophy. RESULTS: Adverse drug effects, opportunistic
      infections and malignancies as well as immune-reconstitution syndrome were ruled
      out based on history and laboratory data. The exact pathophysiological mechanisms
      of ataxia in HIV patients is not very clear, but seems to be immune-mediated or a
      direct neurotoxic virus effect leading to apoptosis of Purkinje and granular
      cells. CONCLUSION: HIV infection should be investigated in adult patients with
      undetermined sporadic progressive pure ataxia with cerebellar atrophy.

PMID- 29643008
TI  - Patterned cortical atrophy in early Parkinson's Disease: The potential for
      unbiased, data driven neuroimaging to detect structural changes in de novo
      patients.

PMID- 29643007
TI  - The diagnostic accuracy of the hummingbird and morning glory sign in patients
      with neurodegenerative parkinsonism.
AB  - INTRODUCTION: The hummingbird sign and the morning glory flower sign, reflecting
      midbrain pathology on MRI, have previously been shown to separate patients with
      progressive supranuclear palsy (PSP) from those with Parkinson's disease (PD) and
      multiple system atrophy (MSA). The aim of the present study was to determine the
      diagnostic accuracy and reproducibility of visual assessment of midbrain atrophy
      patterns in a large cohort of patients with neurodegenerative parkinsonism.
      METHODS: Retrospective analysis of midbrain atrophy patterns on T1-weighted MRI
      in a large cohort of patients with neurodegenerative parkinsonism and healthy
      controls who underwent MR imaging during their diagnostic work-up. RESULTS: 481
      patients with neurodegenerative parkinsonism and 79 healthy controls were
      included in the present study. The presence of the hummingbird sign had a
      specificity of 99.5% and a positive predictive value of 96.1% for a diagnosis of
      PSP while sensitivity was suboptimal with 51.6%. Similarly, the presence of the
      morning glory flower sign yielded a specificity of 97.7% for a diagnosis of PSP,
      but sensitivity was only 36.8%. Sensitivity of both signs was 35.3% in early,
      clinically unclassifiable parkinsonism. Visual assessment of these midbrain
      alterations showed excellent inter-rater agreement. CONCLUSION: Midbrain atrophy
      patterns are useful in the differential diagnosis of neurodegenerative
      parkinsonism but both the hummingbird sign and more so the morning glory flower
      sign suffer from low sensitivity, especially in early disease stages.

PMID- 29643009
TI  - Development of a novel recycling system for waste cathode ray tube funnel glass
      based on the integration of nanoscale Fe0 with ball milling.
AB  - A novel and effective system was developed for recycling cathode ray tube (CRT)
      funnel glass wastes. Initially, the combination of nanoscale Fe0 with ball
      milling promoted lead transfer that was strongly encapsulated in the glass inner
      structure to the surface of funnel glass and/or adhere to iron substance due to
      the collapse of SiO bonds. This condition enhanced the dissolution of lead in the
      acid solution. A high lead extraction rate of 97.8% from funnel glass was
      achieved through nitric acid leaching by optimizing the operational parameters
      (Fe0/funnel glass mass ratio, 0.5:1; ball milling time; 72 h). Subsequently, lead
      sulfate, iron hydroxides, and sodium nitrate were gradually recovered from the
      acid leachate by using three simple operations, namely, sulfation, alkali
      neutralization, and salt evaporation. Meanwhile, the leaching results of short
      term toxicity characteristic leaching (TCLP) and long-term multiple extraction
      procedures (MEP) clearly demonstrated that the residual high silica products
      (after acid leaching) had no impact on the environment and could be used to
      synthesize high value-added zeolites as raw materials. With the addition of Al
      sources, the complete conversion of high silica residues into high crystalline
      zeolites with high cation exchange capacity value was realized by applying an
      alkaline fusion method during the hydrothermal treatment. Furthermore, lead, NO
      3, and SO2-4 concentrations of the resulting drainage were considerably lower
      than the relevant standard for surface water quality. Therefore, the proposed
      recycling system provided an eco-friendly and feasible technique for complete
      reutilization of obsolete CRT funnel glass.

PMID- 29643010
TI  - Development of the global schizophrenia research under epidemiological and socio
      economic influences.

PMID- 29643011
TI  - The effect of antiretroviral intensification with dolutegravir on residual virus
      replication in HIV-infected individuals: a randomised, placebo-controlled, double
      blind trial.
AB  - BACKGROUND: Whether ongoing virus replication occurs in HIV-infected individuals
      on antiretroviral therapy (ART) is unclear; therefore, whether residual virus
      replication is a barrier to achieving a cure for HIV is also unknown. We aimed to
      establish whether ART intensification with dolutegravir would reveal or affect
      residual virus replication in HIV-infected individuals on suppressive treatment.
      METHODS: In this randomised, placebo-controlled, double-blind trial, we enrolled
      HIV-infected adults (aged 18 years and older) receiving combination ART (at least
      three agents) for at least 3 years from the Alfred Hospital and Melbourne Sexual
      Health Centre, Melbourne, VIC, Australia. Eligible participants had fewer than 50
      copies per mL HIV-1 plasma RNA for more than 3 years and fewer than 20 copies per
      mL at screening and two CD4 counts higher than 350 cells per MUL in the previous
      24 months including screening. Participants were randomly assigned (1:1) to
      receive 50 mg oral dolutegravir or placebo once a day for 56 days in addition to
      background ART. Follow-up was done at days 1, 3, 7, 14, 28, 56, and 84. The
      primary outcome was the change from baseline in frequency of 2-long terminal
      repeat (2-LTR) circles in peripheral blood CD4 cells at day 7. This trial is
      registered with ClinicalTrials.gov, number NCT02500446. FINDINGS: Between Sept
      21, 2015, and Sept 19, 2016, 46 individuals were screened for inclusion. 40 were
      eligible for inclusion and were randomly assigned to the dolutegravir (n=21) or
      placebo group (n=19). All enrolled participants completed the study procedures
      and no individuals were lost to follow up. All participants were on suppressive
      ART with 12% receiving protease inhibitors and the others non-nucleoside reverse
      transcriptase inhibitors. Median 2-LTR circles fold-change from baseline to day 7
      was -0.17 (IQR -0.90 to 0.90) in the dolutegravir group and -0.26 (-1.00 to 1.17)
      in the placebo group (p=0.17). The addition of dolutegravir to pre-existing ART
      regimens was safe and there were no treatment discontinuations or treatment
      related serious adverse events. INTERPRETATION: Our findings show that in HIV
      infected individuals on modern suppressive ART regimens, residual replication is
      rare, if at all present, and was not recorded in blood after dolutegravir
      intensification. Because tissue biopsies were not done we cannot exclude the
      possibility of residual virus replication in tissue. Strategies other than ART
      alone are needed to eliminate HIV persistence on treatment. FUNDING: ViiV
      Healthcare.

PMID- 29643012
TI  - Dolutegravir intensification and HIV persistence: 3 + 1 = 3.

PMID- 29643014
TI  - The Real World Dilemma.

PMID- 29643015
TI  - About Image Manipulation of the CTA on Software to Simulate the Appropriate Intra
      operative C-arm Position.

PMID- 29643013
TI  - Circulating Micrornas Predict Survival of Patients with Tumors of Glial Origin.
AB  - The World Health Organization has recently introduced molecular prognostic
      diagnostic biomarkers in the classification of Central Nervous System (CNS)
      tumors. In order to characterize subclasses of tumors that cannot find a precise
      location in the current classification, and, or cannot be tested because of scant
      material, it is important to find new molecular biomarkers in tissue and, or
      biological fluid samples. In this study, we identified serum microRNAs that could
      serve as biomarkers for the diagnosis and prognosis of patients with tumors of
      glial origin. We retrospectively analyzed microRNA expression in the serum
      extracellular vesicles of patients with tumors of glial origin. Extracellular
      vesicles RNA was analyzed by Nanostring. qRT-PCR confirmed 6 overexpressed
      microRNAs: hsa-miR-4443, hsa-miR-422a, hsa-miR-494-3p, hsa-miR-502-5p, hsa-miR
      520f-3p, and hsa-miR-549a. Hsa-miR-4443 was the only microRNA that showed
      significant differences in most comparisons. In situ hybridization (ISH),
      confirmed that our signature was mostly expressed in cancer cells. Importantly,
      hsa-miR-549a and hsa-miR-502-5p expression predicted prognosis in patients with
      tumors of glial origin. Although more studies are needed, we demonstrated that
      serum vesicles microRNA profiles are promising diagnostic and prognostic
      molecular biomarkers that will find an actual application in the clinical
      practice of CNS tumors.

PMID- 29643016
TI  - Development and Validation of a Predictive Model to Aid in the Management of
      Intact Abdominal Aortic Aneurysms.
AB  - OBJECTIVE/BACKGROUND: Predicting outcomes prior to elective abdominal aortic
      aneurysm repair (AAA) requires critical decision making, as the treatment offered
      is a prophylactic procedure to prevent death from a ruptured AAA. The aim of this
      work was to develop and validate a model that may predict outcomes for patients
      with an AAA and hence aid in clinical decision making. METHODS: A discrete event
      simulation model was built to simulate the natural history of a patient with an
      AAA and to predict the 30 day and 2-5 year survival of patients undergoing
      treatment and surveillance. The input parameters of AAA behavior and impact of
      comorbidities on survival were derived from the published literature and the New
      Zealand national life tables. The model was externally validated using a cohort
      of patients that underwent AAA repair (n = 320) and a cohort of patients
      undergoing small AAA surveillance (n = 376). All patients had completed at least
      5 years of follow up. RESULTS: The model was run three times for each data set to
      test. This produced a SD < 1%, indicating excellent reproducibility. The observed
      30 day mortality for the patients undergoing AAA repair was 9/320 (2.8%) and the
      expected (model predicted) mortality was 3.8% (c-statistic 0.87 [95 confidence
      interval 0.75-1.0]). The c-statistic for the predicted 2-5 year survival ranged
      from 0.68 to 0.71 for the repaired AAA cohort and 0.69 to 0.73 for patients with
      a small AAA on surveillance. CONCLUSION: The AAA clinical decision tool has the
      ability to accurately predict the 5 year survival of patients with an AAA. This
      tool can be used during clinical decision making to better inform clinicians and
      patients of long-term outcomes. Further validation studies in a wider AAA
      population are required to test the broader clinical utility of this AAA clinical
      decision tool.

PMID- 29643017
TI  - The Importance of Expert Opinion-Based Data: Lessons from the European Paediatric
      Association/Union of National European Paediatric Societies and Associations
      (EPA/UNEPSA) Research on European Child Healthcare Services.

PMID- 29643020
TI  - Information for Readers.

PMID- 29643021
TI  - Keeping track of sound objects in space: The contribution of early-stage auditory
      areas.
AB  - The influential dual-stream model of auditory processing stipulates that
      information pertaining to the meaning and to the position of a given sound object
      is processed in parallel along two distinct pathways, the ventral and dorsal
      auditory streams. Functional independence of the two processing pathways is well
      documented by conscious experience of patients with focal hemispheric lesions. On
      the other hand there is growing evidence that the meaning and the position of a
      sound are combined early in the processing pathway, possibly already at the level
      of early-stage auditory areas. Here, we investigated how early auditory areas
      integrate sound object meaning and space (simulated by interaural time
      differences) using a repetition suppression fMRI paradigm at 7 T. Subjects listen
      passively to environmental sounds presented in blocks of repetitions of the same
      sound object (same category) or different sounds objects (different categories),
      perceived either in the left or right space (no change within block) or shifted
      left-to-right or right-to-left halfway in the block (change within block).
      Environmental sounds activated bilaterally the superior temporal gyrus, middle
      temporal gyrus, inferior frontal gyrus, and right precentral cortex. Repetitions
      suppression effects were measured within bilateral early-stage auditory areas in
      the lateral portion of the Heschl's gyrus and posterior superior temporal plane.
      Left lateral early-stages areas showed significant effects for position and
      change, interactions Category x Initial Position and Category x Change in
      Position, while right lateral areas showed main effect of category and
      interaction Category x Change in Position. The combined evidence from our study
      and from previous studies speaks in favour of a position-linked representation of
      sound objects, which is independent from semantic encoding within the ventral
      stream and from spatial encoding within the dorsal stream. We argue for a third
      auditory stream, which has its origin in lateral belt areas and tracks sound
      objects across space.

PMID- 29643022
TI  - Involuntary and voluntary electroconvulsive therapy: A case-control study.
AB  - BACKGROUND: It is not known whether results of clinical research in ECT can be
      used to guide treatment decisions for those having involuntary ECT, who are not
      represented in trial populations. OBJECTIVE: We aimed to compare courses of
      involuntary ECT with matched voluntary ECT courses in terms of clinical and
      demographic factors, treatment requirements, and outcomes. METHOD: We performed a
      retrospective case-control study examining a five-year sample of involuntary ECT
      courses and an age-, gender- and time-matched voluntary ECT control sample.
      RESULTS: We examined 48 involuntary and 96 control voluntary ECT courses. While
      groups differed at baseline in terms of diagnosis, illness severity and illness
      characteristics, there were no differences in treatment outcomes after ECT or six
      month readmission rates. CONCLUSION: Our findings suggest that research on
      capacitous ECT patients is applicable to those having involuntary ECT.

PMID- 29643023
TI  - Effective School Health Service: A Response to Adolescent Health Needs in Europe.

PMID- 29643025
TI  - Information for Readers.

PMID- 29643027
TI  - [Purtscher-like retinopathy associated with antibiotic anaphylaxis].
AB  - OBJECTIVE: We report a case of an 18-year-old woman with systemic antibiotic
      anaphylaxis who presented anasarca and bilateral visual loss two weeks after the
      intravenous use of pazufloxacin. Ancillary fundus tests revealed bilateral cotton
      wool spots, Purtscher flecken, edema, and retinal arteriolar occlusion around the
      optic disc. After pulse corticosteroid, administration of anti-anaphylactic
      agent, and general support therapy for one month, the patient showed a favorable
      change, with the symptoms lessened or free systemically, except the continuous
      aggravation of fundus ischemic change. After two intravitreal injections of
      Ranibizumab, there were still a large area of capillary non-perfusion and
      neovacularizations in the binocular retina, resulting in vitreous hemorrhage. The
      patient's visual acuity had still light perception after right-eye vitrectomy and
      presented no improvement during the postoperative follow-up of two years.
      Literature review revealed that there were many causes associated with Purtscher
      like retinopathy, and the consequent visual impairment varied significantly.
      Prompt management of the underlying condition is crucial in giving the patient
      the best chance to restore vision.

PMID- 29643028
TI  - [Chrysin inhibits lipopolysaccharide-induced inflammatory responses of
      macrophages via JAK-STATs signaling pathway].
AB  - OBJECTIVE: To investigate the mechanism of chrysin in regulating
      lipopolysaccharide (LPS)-induced inflammation in RAW264.7 cells. METHODS:
      RAW264.7 cells were treated with different concentrations (0, 5, 10, 20, 40, 60,
      80, 100, 150, and 200 ug/mL) of chrysin for 24 h, and the cell viability was
      measured using CCK-8. RAW264.7 cells were pre-treated with 10, 30, or 60 ug/mL
      chrysin for 2 h before stimulation with LPS for different times. The levels of
      TNF-alpha, IL-6 and MCP-1 were detected by ELISA, and Western blotting was used
      to detect the phosphorylation of JAK- 1, JAK-2, STAT-1 and STAT-3. The level of
      reactive oxygen species in RAW264.7 cells was detected by CM-H2DCFDA fluorescence
      probe. The effect of ROS on LPS-induced JAK-STATs signal and the inflammatory
      response of RAW264.7 cells was detected by ROS scavenger NAC. The transcription
      factors STAT-1 and STAT-3 nuclear translocation were observed by laser confocal
      microscopy. RESULTS: Chrysin below 60 ug/mL did not significantly affect the
      viability of RAW264.7 cells. At 10, 30, and 60 ug/mL, chrysin dose-dependently
      inhibited the expression of iNOS induced by LPS. Chrysin treatment also inhibited
      LPS-induced phosphorylation of JAK-STATs, nuclear translocation of STAT1 and
      STAT3, release of TNF-alpha, IL-6 and MCP-1, and the production of ROS in
      RAW264.7 cells; ROS acted as an upstream signal to mediate the activation of JAK
      STATs signaling pathway. CONCLUSION: Chrysin blocks the activity of JAK-STATs
      mediated by ROS to inhibit LPS-induced inflammatory response in RAW264.7 cells.

PMID- 29643029
TI  - [A machine learning model based on initial gut microbiome data for predicting
      changes of Bifidobacterium after prebiotics consumption].
AB  - OBJECTIVE: To investigate the effects of prebiotics supplementation for 9 days on
      gut microbiota structure and function and establish a machine learning model
      based on the initial gut microbiota data for predicting the variation of
      Bifidobacterium after prebiotic intake. METHODS: With a randomized double-blind
      self-controlled design, 35 healthy volunteers were asked to consume fructo
      oligosaccharides (FOS) or galacto-oligosaccharides (GOS) for 9 days (16 g per
      day). 16S rRNA gene high-throughput sequencing was performed to investigate the
      changes of gut microbiota after prebiotics intake. PICRUSt was used to infer the
      differences between the functional modules of the bacterial communities. Random
      forest model based on the initial gut microbiota data was used to identify the
      changes in Bifidobacterium after 5 days of prebiotic intake and then to build a
      continuous index to predict the changes of Bifidobacterium. The data of fecal
      samples collected after 9 days of GOS intervention were used to validate the
      model. RESULTS: Fecal samples analysis with QIIME revealed that FOS intervention
      for 5 days reduced the intestinal flora alpha diversity, which rebounded on day
      9; in GOS group, gut microbiota alpha diversity decreased progressively during
      the intervention. Neither FOS nor GOS supplement caused significant changes in
      beta diversity of gut microbiota. The area under the curve (AUC) of the
      prediction model was 89.6%. The continuous index could successfully predict the
      changes in Bifidobacterium (R=0.45, P=0.01), and the prediction accuracy was
      verified by the validation model (R=0.62, P=0.01). CONCLUSION: Short-term
      prebiotics intervention can significantly decrease alpha-diversity of the
      intestinal flora. The machine learning model based on initial gut microbiota data
      can accurately predict the changes in Bifidobacterium, which sheds light on
      personalized nutrition intervention and precise modulation of the intestinal
      flora.

PMID- 29643030
TI  - [Screening and verification of key genes in T-cell acute lymphoblastic leukemia].
AB  - OBJECTIVE: To explore the key genes in T-cell acute lymphoblastic leukemia (T
      ALL) using bioinformatics method to better understand the pathogenic mechanisms
      of T-ALL. METHODS: The gene expression profiles of GSE14317 were obtained from
      Gene Expression Omnibus database. The differentially expressed genes (DEGs) in T
      ALL were analyzed using R package Limma. The online analysis tool DAVID was used
      to perform the functional and pathway enrichment analysis. The protein-protein
      interaction network was constructed by STRING and visualized by Cytoscape. Based
      on the JASPAR database, the transcription factors (TFs) of the hub genes were
      obtained. RT-PCR was used to test the mRNA expression level of the key genes.
      RESULTS: A total of 1443 DEGs were identified, including 800 up-regulated genes
      and 643 down-regulated genes. These DEGs were significantly enriched in the cell
      cycle, hematopoietic cell lineage, cytokine-cytokine receptor interaction and T
      cell receptor signaling pathway. The top 10 hub genes identified from the PPI
      networks included CDK1, PIK3R1, CCNB1, CCNA2, CDC20, JUN, GNG11, PLK1, PCNA and
      CCNB2, which were enriched in chemokine signaling pathway, ubiquition mediated
      proteolysis and cell cycle. In the TF-target gene network, 42 differentially
      expressed TFs were identified, among which ELF5, HIC2 and MEISI had binding sites
      with 9 of the candidate hub genes. RT-PCR showed that the mRNA expression level
      of all the candidate hub genes except for GNG11 were consistent with the gene
      expression profiles. CONCLUSION: The hub genes CDK1, PIK3R1, CCNB1, CCNA2, CDC20,
      JUN, PLK1, PCNA, CCNB2, ELF5, HIC2 and MEISI participate in the occurrence of T
      ALL. Our finding provides new insights into the pathogenesis of T-ALL.

PMID- 29643031
TI  - [Role of p38MAPK signaling pathway in autophagy of Henle-407 cells induced by
      spvB of Salmonella typhimurium].
AB  - OBJECTIVE: To investigate the role of p38MAPK signaling pathway in autophagy of
      intestinal epithelial cells induced by spvB of S.typhimurium. METHODS: Henle-407
      cells in exponential growth were infected with wild-type S.typhimurium strain STM
      211 (with spvB gene), spvB mutated strain STM-delata;spvB, or with delata;spvB
      complemented strain STM-c-spvB after treatment of the cells with the p38MAPK
      inhibitor SB203580. At different time points of co-culture, the cells were
      collected and the intracellular bacteria were counted. Western blotting was
      performed to detect the expressions of phosphorylated p38 and autophagy-related
      proteins LC3 and p62; immunofluorescence staining was used to observe the
      expression and distribution of LC3. RESULTS: At 1, 2 and 4 h after the infection,
      the phosphorylation levels of p38 in STM-211 group and STM-c-spvB group were
      significantly lower than that in STM-delata;spvB group (P<0.05). At 2 and 4 h of
      co-culture, the intracellular bacterial counts were significantly greater in STM
      211 and STM-c-spvB infection groups than in STM-delata;spvB group (P<0.05).
      Pretreatment with p38 inhibitor SB203580 did no significantly affect the
      expression levels of LC3 II or P62 in STM-211 and STM-c-spvB groups, but caused
      significant reduction in their expressions in STM-delata;spvB group at 1 h
      (P<0.05), and such changes were more obvious at 3 h (P<0.05). CONCLUSION: The
      inhibitory effect of spvB gene on autophagy in intestinal epithelial cells is
      related with the negative regulation of p38MAPK signaling pathway.

PMID- 29643032
TI  - [Regulatory role of Shh signaling pathway in lung development in fetal mice].
AB  - OBJECTIVE: To investigate the regulatory role of classical Shh signaling pathway
      in the development of the epithelium and mesenchyme (bronchial cartilage and
      smooth muscles) during lung development in fetal mice. METHODS:
      Immunohistochemical technique was used to detect the expression of Shh signaling
      pathway receptor Smo and Pdgfr-alpha in murine fetal lungs to explore the spatial
      and temporal characteristics of their expression. Based on the interstitial
      specificity of Pdgfr-alpha expression, we constructed a Pdgfr-alpha-cre to
      establish a E12.5 - E16.5 transgenic mice with specific knockout of the key Shh
      signaling molecule Smo in the pulmonary interstitium with tamoxifen induction.
      Immunofluorescence technique was used to observe the epithelium and mesenchyme
      (bronchial cartilage and smooth muscle) during fetal lung development in the
      transgenic mice to assess the role of Shh signaling pathway in the epithelial-to
      mesenchymal (EMT) transition during the lung development. RESULTS: Smo was highly
      expressed in the epithelial and stromal lung tissues in the pseudoglandular stage
      and was gradually lowered over time with its distribution mainly in the
      interstitial tissues. Pdgfr-alpha was enriched in the distal lung epithelial and
      mesenchy tissues in early embryonic lungs and gradually migrated to the proximal
      stroma until becoming concentrated around the main bronchial proximal stroma. We
      successfully specific established mouse models of specific mesenchymal Smo
      knockout. Compared with the control group, the transgenic mice during E12.5-E16.5
      showed significantly reduced lung the volume and bronchial branching with also
      decreased expression of the proximal epithelial P63 (P<0.05). The transgenic mice
      exhibited alterations in the expression of alpha-smooth muscle actin with delayed
      bronchial cartilage development and decreased expression of mucoprotein.
      CONCLUSION: The temporospatial specific expression of Shh signaling pathway plays
      an important role in developmental regulation of mouse embryonic lung epithelium
      and mesenchyme (bronchial cartilage and smooth muscle).

PMID- 29643033
TI  - [Vaspin protects against lipopolysaccharide-induced acute respiratory distress
      syndrome in mice by inhibiting inflammation and protecting vascular endothelium
      via PI3K/Akt signal pathway].
AB  - OBJECTIVE: To investigate the effects of Vaspin on lipopolysaccharide (LPS)
      induced acute respiratory distress syndrome (ARDS) in mice and explore the
      possible mechanism. METHODS: Forty male C57B/L6 mice were randomized equally into
      control group, LPS group, Vaspin group and wortmannin group with corresponding
      treatments. The pathological changes of the lung tissues were evaluated by HE
      staining, and the severity of pulmonary edema was measured according to the
      wet/dry ratio (W/D) of the lung tissue. The lung permeability was evaluated by
      detecting total protein concentrations in the bronchoalveolar lavage fluid (BALF)
      using bicinchoninic acid (BCA) assay. Myeloperoxidase (MPO) activity in the lung
      tissue was detected using a MPO assay kit, and the levels of interleukin-1beta
      (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) in the lungs were measured
      using ELISA. Immunohistochemical staining was performed to detect the expression
      of vascular cell adhesion molecule-1 (VCAM-1) and Western blotting was used to
      detect the protein expressions of cleaved caspase-3 and p-Akt in the lung
      tissues. RESULTS: Compared with the control group, the mice in LPS group
      displayed typical ARDS pathological changes in the lungs with significantly
      increased W/D, total protein concentrations in BALF, lung MPO activity, levels of
      IL-1beta and TNF-alpha, and pulmonary expressions of VCAM-1 and cleaved caspase-3
      (P<0.05) but decreased expression of p-Akt (P<0.05). These changes induced by LPS
      were significantly alleviated by the administration of Vaspin (P<0.05). The
      protective effects of Vaspin against ARDS were obviously attenuated by the PI3K
      inhibitor wortmannin (P<0.05). CONCLUSION: Vaspin protects against LPS-induced
      ARDS in mice possibly by inhibiting inflammation and protecting vascular
      endothelium through upregulation of the PI3K/Akt signal pathway.

PMID- 29643034
TI  - [Verification of a sporadic Alzheimer disease model in SORL1 gene knockout mice].
AB  - OBJECTIVE: To compare the behavioral and pathological features of SORL1 gene
      knockout mice with those of normal mice and APP/PSE1 mice to verify the
      feasibility of using SORL1 knockout mice as a model of sporadic Alzheimer
      disease. METHODS: SORL1 gene of fertilized mouse eggs were edited using
      Crispr/Case9 technique. SORL1-/- mice were screened and identified by detecting
      the DNA sequence, and Western blotting was used to detect the expression of
      SORL1. SORL1-/- mice, control mice and APP/PSE1 mice all underwent Morris water
      maze test to assess their learning and memory abilities with positioning
      navigation and space exploration experiments. The expression of APP and Abeta in
      the brain of the mice was detected using immunohistochemistry and Western
      blotting, respectively. RESULTS: DNA sequencing showed CAAT deletion in SORL1
      gene in two chromosomes of SORL1-/- mice, and the control mice had intact SORL1
      gene without the deletion; Western blotting did not detect the expression of the
      SORL1 in the brain of SORL1-/- mice. Morris water maze test showed that in
      positioning navigation experiment, the average avoidance latency was similar
      between SORL1-/- mice and APP/PSE1 mice (P>0.05) but increased significantly in
      both mice as compared with the control group (P<0.05); similar results were
      obtained in the space exploration experiment. Immunohistochemistry and Western
      blotting revealed significantly increased APP and Abeta expression in the brain
      tissue of both SORL1-/- mice and APP/PSE1 mice compared with the control mice
      without significant differences between the two transgenic mice. CONCLUSION:
      SORL1-/- mice exhibit similar behavioral and pathological changes with APP/PSE1
      mice and can be used as a model of sporadic Alzheimer's disease.

PMID- 29643035
TI  - [Correlation between expressions of VEGF and TRPC6 and their roles in podocyte
      injury in rats with diabetic nephropathy].
AB  - OBJECTIVE: To analyze the correlation between the expressions of vascular
      endothelial growth factor (VEGF) and transient receptor potential canonical 6
      (TRPC6) and their role in podocyte injury in rats with diabetic nephropathy.
      METHODS: Forty SD rats with diabetic nephropathy induced by intraperitoneal
      injection of 65 mg/kg streptozotocin were randomized equally into 5 groups,
      including a diabetic nephropathy model group and 4 treatment groups, with 8
      normal SD rats as the normal control group. In the 4 treatment groups, the rats
      received intraperitoneal injections with SU5416 at 5 mg/kg or 10 mg/kg twice a
      week or with LY294002 at 1 mg/kg or 2 mg/kg once daily for 8 weeks. Blood
      glucose, serum creatinine, blood urea nitrogen, and 24-h urinary protein levels
      of the rats were detected at different time points, and the pathologies in the
      renal tissue were observed using HE staining, PAS staining and
      immunohistochemistry. The expressions of VEGF, nephrin, and TRPC6 at mRNA and
      protein levels were detected using RT-PCR and Western blotting. RESULTS: Compared
      with normal control rats, the diabetic rats showed significantly increased
      fasting blood glucose, serum creatinine, blood urea nitrogen and 24-h urinary
      protein levels with decreased expressions of nephrin mRNA and protein (P<0.05)
      and increased expressions of VEGF and TRPC6 (P<0.05). Compared with the untreated
      diabetic rats, the rats with SU5416 treatment showed increased 24-h urinary
      protein, urea nitrogen, and nephrin expression and decreased TRPC6 expression
      without significant changes in fasting blood glucose, serum creatinine, or VEGF
      expression. The rats treated with LY294002 showed decreased 24-h urinary protein
      and TRPC6 expression without significant changes in fasting blood glucose, serum
      creatinine, urea nitrogen, or expressions of nephrin and VEGF. CONCLUSION: The
      regulatory effect of VEGF on TRPC6 can be blocked by inhibiting VEGFR-2 or
      blocking PI3K/Akt signaling pathway.

PMID- 29643036
TI  - [Quantitative magnetic resonance imaging of brain iron deposition: comparison
      between quantitative susceptibility mapping and transverse relaxation rate (R2*)
      mapping].
AB  - OBJECTIVE: To evaluate the accuracy and sensitivity of quantitative
      susceptibility mapping (QSM) and transverse relaxation rate (R2*) mapping in the
      measurement of brain iron deposition. METHODS: Super paramagnetic iron oxide
      (SPIO) phantoms and mouse models of Parkinson's disease (PD) related to iron
      deposition in the substantia nigra (SN) underwent 7.0 T magnetic resonance (MR)
      scans (Bruker, 70/16) with a multi-echo 3D gradient echo sequence, and the
      acquired data were processed to obtain QSM and R2*. Linear regression analysis
      was performed for susceptibility and R2* in the SPIO phantoms containing 5 SPIO
      concentrations (30, 15, 7.5, 3.75 and 1.875 ug/mL) to evaluate the accuracy of
      QSM and R2* in quantitative iron analysis. The sensitivities of QSM and R2*
      mapping in quantitative detection of brain iron deposition were assessed using
      mouse models of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahy-dropyridine
      (MPTP) in comparison with the control mice. RESULTS: In SPIO phantoms, QSM
      provided a higher accuracy than R2* mapping and their goodness-of-fit
      coefficients (R2) were 0.98 and 0.89, respectively. In the mouse models of PD and
      control mice, the susceptibility of the SN was significantly higher in the PD
      models (5.19?1.58 vs 2.98?0.88, n=5; P<0.05), while the R2* values were similar
      between the two groups (20.22?0.94 vs 19.74?1.75; P=0.60). CONCLUSION: QSM allows
      more accurate and sensitive detection of brain iron deposition than R2*, and the
      susceptibility derived by QSM can be a potentially useful biomarker for studying
      PD.

PMID- 29643037
TI  - [Screening active ingredients of Shenkangwan that regulate endothelial
      mesenchymal transition of endothelial cells in vitro].
AB  - OBJECTIVE: To screen the effective components of Shenkangwan that regulate
      endothelial-mesenchymal transition in endothelial cells for optimizing
      prescription of Shenkangwan. METHODS: ALK5 was identified as one of the target
      receptors that regulate endothelial-mesenchymal transition of endothelial cells
      using molecular docking technique. Nine molecules were screened as the candidate
      effective components in Shenkangwan, among which calycosin, ononin and
      stigmasterol were selected for testing. Glomerular epithelial cells were exposed
      to high glucose and treated with calycosin, ononin, or stigmasterol, and the
      cellular expressions of alpha-smooth muscle actin (alpha-SMA) and vimentin mRNA
      were detected with real-time fluorescence quantitative PCR. The phosphorylation
      of SMAD2/3 in the cells was detected using Western blotting. RESULTS: Calycosin,
      ononin and stigmasterol did not produce significant cytotoxicity in glomerular
      epithelial cells (P>0.05). The cells exposed to high glucose and calycosin
      treatment showed significantly decreased mRNA levels of alpha-SMA and vimentin
      (P<0.05) and inhibited phosphorylation of SMAD2/3. Ononin and stigmasterol did
      not produce such effects in the cells. CONCLUSION: In endothelial cells with high
      glucose-induced injury, calycosin can inhibit the up-regulation of alpha-SMA and
      vimentin and inhibit phosphorylation of SMAD2/3 to regulate endothelial
      mesenchymal transition and improve diabetic nephropathy.

PMID- 29643038
TI  - [Effects of minimally invasive versus open esophagectomy on circulating tumor
      cells in patients with esophageal cancer].
AB  - OBJECTIVE: To investigate the effects of minimally invasive esophagectomy (MIE)
      and open esophagectomy (OE) on the level of circulating tumor cells (CTCs) in
      patients with esophageal cancer (EC). METHODS: A total of 73 patients with EC
      undergoing MIE (n=38) or OE (n=35) in our department between October, 2015 and
      October, 2017 were enrolled, with 10 patients with benign esophagus disease and
      10 healthy volunteers as controls. The levels of CTCs in the peripheral blood of
      the participants were detected using CanPatrolTM technique and analyzed for their
      association with the operation methods and perioperative complications. RESULTS:
      CTCs were detected in 60.3% (44/73) of the EC patients but in none of the control
      subjects. CTC level after the surgery was significantly higher than that during
      the surgery, and CTC level during the surgery was significantly higher than that
      before surgery (P<0.001). The preoperative and intra-operative CTC levels were
      not significantly different between MIE and OE groups (P>0.05), but the
      postoperative CTC level was significantly lower in MIE group than in OE group,
      and postoperative increment of CTC level (from the preoperative level) was
      significantly lower in MIE group than in OE group (P<0.001). The total incidence
      of postoperative complications was significantly lower in MIE group than in OE
      group (28.9% vs 54.3%, P=0.023), and in both groups, CTC levels in patients with
      complications were significantly higher than those in patients without
      complications (P=0.001 and P=0.005 in MIE and OE groups, respectively).
      CONCLUSION: MIE may help to reduce the number of peripheral blood CTCs early
      after the operation, and dynamic monitoring CTCs level assists in evaluation of
      the prognosis of EC patients. CTC level may serve as an indicator for monitoring
      the prognosis of EC.

PMID- 29643039
TI  - [Expression of DKKL1 in spermatozoa of men with asthenospermia].
AB  - OBJECTIVE: To compare the expression of DKKL1 in ejaculated spermatozoa of normal
      fertile men and men with asthenospermia and investigate the role of DKKL1 in the
      pathogenesis of asthenospermia. METHODS: The characteristics of semen samples
      collected from normal fertile men and men with asthenospermia were analyzed using
      computer-assisted sperm analysis according to WHO criteria. The ejaculated sperms
      were isolated by Percoll discontinuous density gradients to detect the expression
      of DKKL1 mRNA and protein using real-time PCR and Western blotting. RESULTS: The
      expression of DKKL1 mRNA was significantly down-regulated by 11.1 times in
      asthenospermic men as compared with that in normal fertile men (P<0.01). Western
      blotting showed that the expression of DKKL1 protein was down-regulated by 2.4
      times in asthenospermic men compared to normal fertile men. CONCLUSION: The
      expression of DKKL1, which may play an important role in sperm motility,is
      significantly decreased in ejaculated spermatozoa of men with asthenospermia.

PMID- 29643040
TI  - [Value of CHCHD2 as a potential marker of non-small cell lung cancer: analysis of
      60 cases].
AB  - OBJECTIVE: To investigate the expression of CHCHD2, a potential tumor marker, in
      tumor and adjacent tissues from patients with non-small cell lung cancer (NSCLC).
      METHODS: Immunohistochemistry was used to detect the expression and location of
      CHCHD2 in the tumor tissues from 60 patients with NSCLC and 35 adjacent tissues
      to analyze the correlation of CHCHD2 expression with the clinicopathological
      variables and overall survival of the patients. The expression profile of CHCHD2
      mRNA in NSCLC was analyzed using Oncomine database. RESULTS: The positivity rate
      of CHCHD2 was significantly higher in the tumor tissues than in adjacent tissues
      in patients with NSCLC (75.0% vs 17.1%). CHCHD2 positivity in the tumor tissues
      was associated with lymph node metastasis, pathological TNM stage, and tumor
      grades but not with age, gender, or histological type of the tumors. Analysis
      using Oncomine database showed that CHCHD2 mRNA was expressed at significantly
      higher levels in NSCLC than in normal control group (P<0.05). Kaplan-Meier
      survival analysis showed that NSCLC patients with a positive expression of CHCHD2
      had a significantly shorter overall survival time than those negative for CHCHD2
      (P<0.05). CONCLUSION: As a potential tumor marker, CHCHD2 over-expression plays a
      role in the occurrence and progression of NSCLC and promotes tumor invasion and
      metastasis, and can potentially serve as an indicator for early diagnosis and
      prognostic evaluation of NSCLC.

PMID- 29643041
TI  - [Effect of outer membrane vesicles derived from Escherichia coli on
      proliferation, apoptosis and migration of human neuroblastoma SK-N-SH cells in
      vitro].
AB  - OBJECTIVE: To investigate the effect of outer membrane vesicles derived from
      Escherichia coli on proliferation, apoptosis and migration of human neuroblastoma
      SK-N-SH cells in vitro. METHODS: The outer membrane vesicles (OMVs) were obtained
      from wild-type Escherichia coli with ultracentrifugation method, and the
      morphology of the OMVs was observed by transmission electron microscopy and the
      vesicle diameter was determined using MALVERN ZEN3690. Human neuroblastoma SK-N
      SH cells were treated with the OMVs at low (100 ug/mL), moderate (500 ug/mL) and
      high (1000 ug/mL) doses, and 24, 48 and 72 h later, the cell proliferation
      activity was detected with MTT assay. The expressions of apoptosis-related marker
      caspase-3 was detected using Western blotting, and TUNEL assay was performed to
      detect the cell apoptosis. The migration capacity of SK-N-SH cells was evaluated
      using Transwell migration assay. RESULTS: The isolated OMVs showed a circular or
      elliptical hollow structure with double-layer membrane and a diameter range of 30
      450 nm. Compared with the control cells, SK-N-SH cells treated with the OMVs
      showed significantly lowered cell proliferation capacity with enhanced expression
      of caspase-3. Treatment of the cells with the OMVs resulted in increased cell
      apoptosis and significantly lowered migration capacity (P<0.05). CONCLUSION: The
      OMVs derived from Escherichia coli can produce cytotoxicity against SK-N-SH cells
      and might serve as a therapeutic agent for refractory neuroblastoma.

PMID- 29643042
TI  - [Primary culture of human malignant meningioma cells and its intracranial
      orthotopic transplantation in nude mice].
AB  - OBJECTIVE: To obtain stable primary cultures of human malignant meningioma cells
      and establish an intracranial in-situ tumor model in nude mice. METHODS: Ten
      surgical specimens of highly suspected malignant meningioma were obtained with
      postoperative pathological confirmation. Primary malignant meningioma cells were
      cultured from the tissues using a modified method and passaged. After
      identification with cell immunofluorescence, the cultured cells were inoculated
      into the right parietal lobe of 6 nude mice using stereotaxic apparatus and also
      transplanted subcutaneously in another 6 nude mice. The nude mice were executed
      after 6 weeks, and HE staining and immunohistochmistry were used to detect tumor
      growth and the invasion of the adjacent brain tissues. RESULTS: The primary
      malignant meningioma cells were cultured successfully, and postoperative
      pathology reported anaplastic malignant meningioma. Cell immunofluorescence
      revealed positivity for vimentin and EMA in the cells, which showed a S-shaped
      growth curve in culture. Flow cytometry revealed a cell percentage in the Q3 area
      of (95.99?2.58)%. Six weeks after transplantation, tumor nodules occurred in the
      subcutaneous tumor group, and the nude mice bearing the in situ tumor showed
      obvious body weight loss. The xenografts in both groups contained a mean of
      (36?5.35)% cells expressing Ki-67, and the intracranial in situ tumor showed
      obvious invasion of the adjacent peripheral brain tissues. CONCLUSION: We
      obtained stable primary cultures of malignant meningioma cells and successfully
      established a nude mouse model bearing in situ human malignant meningioma.

PMID- 29643043
TI  - [Shaoyangzhugu Formula regulates p19Arf-p53-p21Cip1 signaling pathway to
      ameliorate cartilage degeneration in aged cynomolgus monkeys with knee
      osteoarthritis].
AB  - OBJECTIVE: To study the effect of Shaoyangzhugu (SYZG) Formula (a formula
      consisting of 9 traditional Chinese drugs) in delaying the degeneration of
      articular cartilage and the role p19Arf-p53-p21Cip1 signaling pathway in
      mediating this effect. METHOD: Thirteen aged cynomolgus monkeys with degenerative
      knee joints were selected based on X-ray findings, and one of them was randomly
      selected for pathological observation. The other monkeys were randomized equally
      into SYZG Formula group (treated with SYZG decoction), ammonia moxime group and
      saline group. All the monkeys were sacrificed after 8 weeks of treatment with
      intragastric administration of the drugs or saline. The pathology in the knee
      joint articular cartilage was observed and the mRNA and protein expressions of
      p19Arf, p53, and p21Cip1 in the articular cartilage were detected using RT-qPCR
      and Western blotting. RESULTS: The pathological findings of the articular
      cartilage in old cynomolgus monkeys were consistent with the characteristics of
      knee osteoarthritis (KOA). Mankin scores of the cynomolgus monkeys were 7.38?0.52
      in SYZG Formula group, 7.88?0.83 in ammonia moxime group, and 8.38?0.74 in saline
      group, showing a significant difference between SYZG Formula group and saline
      group (P<0.05). The expressions of p19Arf, p53, and p21Cip1 were the lowest in
      SYZG Formula group and the highest in saline group with significant differences
      among the 3 groups (P<0.05). CONCLUSION: SYZG Formula can delay chondrocyte
      senescence by regulating p19Arf-p53-p21Cip1 signaling pathway to delay articular
      cartilage degeneration in aged cynomolgus monkeys.

PMID- 29643044
TI  - [Clinical value of genome-wide chromosome microarray technique in diagnosis of
      fetal cerebral ventriculomegaly].
AB  - OBJECTIVE: To investigate the clinical value of gnome-wide chromosome microarray
      (CMA) technique in genetic etiological diagnosis of fetal cerebral
      ventriculomegaly. METHODS: A retrospective analysis was conducted in 109 women
      with singleton pregnancy, who were admitted in Nanfang Hospital with the
      diagnosis of cerebral ventriculomegaly in the fetuses by ultrasound between
      January, 2014 and December, 2016. Routine karyotype analysis and chromosome
      microarray analysis were performed to identify the chromosomal abnormalities in
      the fetuses. RESULTS: Karyotype analysis detected chromosomal abnormalities at a
      rate of 12.84% in these fetuses, significantly lower than the rate of 26.60% with
      CMA technique (P=0.004); the combined detection rate of the two techniques was
      28.44%. In 17 cases, karyotype analysis yielded normal results while CMA
      microarray showed abnormalities with an extra abnormal detection rate of 15.60%.
      Among the 17 fetuses with chromosomal abnormalities, 6 had micro-deletion, 9 had
      micro-duplication, 1 had both micro-deletion and micro-duplication, and 1 had
      heterozygous loss of single parent diploid. CONCLUSION: CMA technique can be used
      to detect abnormal chromosomal copy numbers in fetuses with cerebral
      ventriculomegaly to increase the detection rate of chromosomal abnormalities and
      facilitate prenatal consultation and prognostic evaluation.

PMID- 29643045
TI  - [Effect of 0.9-ms 1064-nm Nd:YAG laser combined with itraconazole for treatment
      of toenail onychomycosis].
AB  - OBJECTIVE: To evaluate the efficacy and safety of 0.9-ms 1064-nm Nd:YAG laser
      alone or combined with itraconazole for treatment of toenail onychomycosis.
      METHODS: A total of 37 patients with onychomycosis (178 toenails) were randomly
      assigned to groups A and B, and each group was further divided into different
      subgroups according to the Scoring Clinical Index of Onychomycosis (SCIO) and
      Onychomycosis Severity Index (OSI) scoring. All the patients were treated with
      0.9-ms Nd:YAG laser once a week for 8 times. The patients in group A were treated
      with laser alone, and those in group B were treated with laser combined with
      itraconazole. The clinical effect, clinical scores, appearance of the toenails
      and adverse reactions in the two groups were analyzed, and the patients'
      satisfaction rate was also investigated. RESULTS: At the 12th months of follow
      up, the clinical response rate and mycological cure rate in group A were 31.33%
      and 30.00%, respectively, similar to the rates in group B (35.79% and 41.18%,
      respectively) (P>0.05). After the treatments, the SCIO and OSI scores showed no
      significant changes in group A (P>0.05) but both increased significantly in group
      B (P<0.05). The response rates did not differ significantly among the subgroups
      with SCIO<12 or with OSI<16 (P>0.05), but showed significant differences among
      the subgroups with SCIO>=12 or with OSI>=16 (P<0.05). Of the total of 178
      toenails, 33.71%, 74.72% and 70.79% toenails showed improvements in terms of
      clear nail growth, shape and color, respectively. The overall patients'
      satisfaction rate was 62.16%, and no adverse reactions related with the therapy
      were recorded in these patients. CONCLUSION: For treatment of toenail
      onychomycosis, 0.9-ms 1064-nm Nd:YAG laser can effectively improve the aesthetic
      appearance of the toenails, and a combined treatment with Nd:YAG laser and
      itraconazole can be better option in severe cases of onychomycosis.

PMID- 29643046
TI  - [Efficacy of dermal scaffold for promoting repair of acute full-thickness skin
      defects in pigs].
AB  - OBJECTIVE: To investigate the efficacy of Lando(r) dermal scaffold for promoting
      repair of acute full-thickness skin defects in pigs and explore the possible
      mechanism. METHODS: Three 5 cm*5 cm full-thickness skin defects were created on
      the left dorsal skin (control group) and another 3 on the right dorsal skin
      (treatment group) of each of 6 Tibetan pigs. The wounds in the treatment group
      were covered with a bilayer artificial skin (Lando) and the control wounds with
      vaseline gauze. In both groups, autogenous split-thickness skin were grafted to
      the wounds 2 weeks later (with the silicone rubber membrane removed before
      grafting in the treatment group). At 3 days and 2 and 10 weeks after the injury,
      the wounds were assessed for general condition and contraction, and tissue
      samples were collected from the wounds to examine the expressions of alpha-smooth
      muscle actin (alpha-SMA) and transforming growth factor-beta1 (TGF-beta1) using
      immunohistochemistry and the expressions of MMP-1 and TIMP-1 mRNA using RT-PCR.
      RESULTS: At 3 days after the injury, the wounds in the 2 groups showed no
      significant differences in the results of any examinations. At 2 weeks after the
      injury, the wounds in the treatment group showed rich and more smooth granulation
      tissues with more regular wound edges compared with the control wounds. At 2 and
      10 weeks after the injury, the wound contraction rates in the treatment group
      were (30.5?3.4)% and (39.2?2.8)%, respectively, significantly lower than the
      rates of (51.8?2.6)% (t=-29.840, P=0.000) and (60.7?2.2)% (t=-50.213, P=0.000) in
      the control group. At 2 weeks, the wound tissues in the treatment group expressed
      significantly higher levels of alpha-SMA (t=15.921, P=0.000) and TGF-beta1
      (t=29.995, P=0.000) than the control wounds, but at 10 weeks, the expressions of
      alpha-SMA (t=-41.823, P=0.000) and TGF-beta1 (t=-99.777, P=0.000) in the
      treatment group were significantly lower than those in the control group.
      Compared with those in the control group, the expression of MMP-1 mRNA in the
      treatment group was significantly lower at 2 weeks (t=-45.412, P=0.000) but
      significantly higher at 10 weeks (t=78.769, P=0.000), and the expression of TIMP
      1 mRNA in the treatment group was significantly lower both at 2 weeks (t=-27.064,
      P=0.000) and at 10 weeks (t=-40.535, P=0.000). CONCLUSIONS: Lando(r) dermal
      scaffold can promote granulation tissue growth possibly in relation with
      increased TGF-beta1 and decreased MMP-1 expression in the wounds. This scaffold
      material also reduces wound contraction and lessens scar hyperplasia and
      contracture after wound healing, probably as a result of decreased alpha-SMA, TGF
      beta1, and TIMP-1 and increased MMP-1 expressions.

PMID- 29643047
TI  - [A case of circulatory collapse during laparoscopic hepatectomy].
AB  - OBJECTIVE: We report a case of intractable circulatory failure event in a
      hypertensive patient during laparoscopy hepatectomy and analyze the diagnosis and
      treatment by multidisciplinary physicians. This case suggests that both surgeons
      and anesthesiologists should give attention to oral angiotensin II receptor
      antagonist during the preoperative period to avoid refractory hypotension. In
      addition, the use of EV1000 hemodynamic monitoring system in intensive care
      provides more convenience for clinical liquid management.

PMID- 29643048
TI  - Exploring the Role of In-Person Components for Online Health Behavior Change
      Interventions: Can a Digital Person-to-Person Component Suffice?
AB  - The growth of the digital environment provides tremendous opportunities to
      revolutionize health behavior change efforts. This paper explores the use of Web
      based, mobile, and social media health behavior change interventions and
      determines whether there is a need for a face-to-face or an in-person component.
      It is further argued that that although in-person components can be beneficial
      for online interventions, a digital person-to-person component can foster similar
      results while dealing with challenges faced by traditional intervention
      approaches. Using a digital person-to-person component is rooted in social and
      behavioral theories such as the theory of reasoned action, and the social
      cognitive theory, and further justified by the human support constructs of the
      model of supportive accountability. Overall, face-to-face and online behavior
      change interventions have their respective advantages and disadvantages and
      functions, yet both serve important roles. It appears that it is in fact human
      support that is the most important component in the effectiveness and adherence
      of both face-to-face and online behavior change interventions, and thoughtfully
      introducing a digital person-to-person component, to replace face-to-face
      interactions, can provide the needed human support while diminishing the barriers
      of in-person meetings. The digital person-to-person component must create
      accountability, generate opportunities for tailored feedback, and create social
      support to successfully create health behavior change. As the popularity of the
      online world grows, and the interest in using the digital environment for health
      behavior change interventions continues to be embraced, further research into not
      only the use of online interventions, but the use of a digital person-to-person
      component, must be explored.

PMID- 29643049
TI  - Evaluation of Technology-Enhanced Learning Programs for Health Care
      Professionals: Systematic Review.
AB  - BACKGROUND: Technology-enhanced learning (TEL) programs are increasingly seen as
      the way in which education for health care professionals can be transformed,
      giving access to effective ongoing learning and training even where time or
      geographical barriers exist. Given the increasing emphasis on this mode of
      educational support for health care practitioners, it is vital that we can
      effectively evaluate and measure impact to ensure that TEL programs are effective
      and fit for purpose. This paper examines the current evidence base for the first
      time, in relation to the evaluation of TEL programs for health care
      professionals. OBJECTIVE: We conducted a systematic review of the current
      literature relating to the evaluation of TEL programs for health care
      professionals and critically appraised the quality of the studies. METHODS: This
      review employed specific search criteria to identify research studies that
      included evaluation of TEL for health care professionals. The databases searched
      included Medline Ovid, Cumulative Index of Nursing and Allied Health Literature
      Plus Advanced, Applied Social Sciences Index and Abstracts, ZETOC, Institute of
      Electrical and Electronics Engineers Explore Digital Library, Allied and
      Complementary Medicine, and Education Resources Information Center between
      January 2006 and January 2017. An additional hand search for relevant articles
      from reference lists was undertaken. Each of the studies identified was
      critically appraised for quality using the Crowe Critical Appraisal Tool. This
      approach produced a percentage total score for each study across specified
      categories. A proportion of the studies were independently assessed by an
      additional two reviewers. RESULTS: The review identified 21 studies that met the
      inclusion criteria. The studies included scored totals across eight categories
      within a range of 37%-95% and an average score of 68%. Studies that measured TEL
      using learner satisfaction surveys, or combined pretest and posttest knowledge
      score testing with learner satisfaction surveys, were found to be the most common
      types of TEL evaluations evident in the literature. The studies reviewed had low
      scores across reporting on ethical matters, design, and data collection
      categories. CONCLUSIONS: There continues to be a need to develop effective and
      standard TEL evaluation tools, and good quality studies that describe effective
      evaluation of TEL education for health care professionals. Studies often fail to
      provide sufficient detail to support transferability or direct future TEL health
      care education programs.

PMID- 29643050
TI  - Jordan Field Epidemiology Training Program: Critical Role in National and
      Regional Capacity Building.
AB  - Field Epidemiology Training Programs (FETPs) are 2-year training programs in
      applied epidemiology, established with the purpose of increasing a country's
      capacity within the public health workforce to detect and respond to health
      threats and develop internal expertise in field epidemiology. The Jordan Ministry
      of Health, in partnership with the US Centers for Disease Control and Prevention,
      started the Jordan FETP (J-FETP) in 1998. Since then, it has achieved a high
      standard of success and has been established as a model for FETPs in the Eastern
      Mediterranean Region. Here we describe the J-FETP, its role in building the
      epidemiologic capacity of Jordan's public health workforce, and its activities
      and achievements, which have grown the program to be self-sustaining within the
      Jordan Ministry of Health. Since its inception, the program's residents and
      graduates have assisted the country to improve its surveillance systems,
      including revising the mortality surveillance policy, implementing the use of
      electronic data reporting, investigating outbreaks at national and regional
      levels, contributing to noncommunicable disease research and surveillance, and
      responding to regional emergencies and disasters. J-FETP's structure and systems
      of support from the Jordan Ministry of Health and local, regional, and
      international partners have contributed to the success and sustainability of the
      J-FETP. The J-FETP has contributed significantly to improvements in surveillance
      systems, control of infectious diseases, outbreak investigations, and
      availability of reliable morbidity and mortality data in Jordan. Moreover, the
      program has supported public health and epidemiology in the Eastern Mediterranean
      Region. Best practices of the J-FETP can be applied to FETPs throughout the
      world.

PMID- 29643051
TI  - How Mobile App Design Impacts User Responses to Mixed Self-Tracking Outcomes:
      Randomized Online Experiment to Explore the Role of Spatial Distance for Hedonic
      Editing.
AB  - BACKGROUND: Goal setting is among the most common behavioral change techniques
      employed in contemporary self-tracking apps. For these techniques to be
      effective, it is relevant to understand how the visual presentation of goal
      related outcomes employed in the app design affects users' responses to their
      self-tracking outcomes. OBJECTIVE: This study examined whether a spatially close
      (vs distant) presentation of mixed positive and negative self-tracking outcomes
      from multiple domains (ie, activity, diet) on a digital device's screen can
      provide users the opportunity to hedonically edit their self-tracking outcome
      profile (ie, to view their mixed self-tracking outcomes in the most positive
      light). Further, this study examined how the opportunity to hedonically edit
      one's self-tracking outcome profile relates to users' future health behavior
      intentions. METHODS: To assess users' responses to a spatially close (vs distant)
      presentation of a mixed-gain (vs mixed-loss) self-tracking outcome profile, a
      randomized 2*2 between-subjects online experiment with a final sample of 397
      participants (mean age 27.4, SD 7.2 years; 71.5%, 284/397 female) was conducted
      in Germany. The experiment started with a cover story about a fictitious self
      tracking app. Thereafter, participants saw one of four manipulated self-tracking
      outcome profiles. Variables of interest measured were health behavior intentions,
      compensatory health beliefs, health motivation, and recall of the outcome
      profile. We analyzed data using chi-square tests (SPSS version 23) and moderated
      mediation analyses with the PROCESS macro 2.16.1. RESULTS: Spatial distance
      facilitated hedonic editing, which was indicated by systematic memory biases in
      users' recall of positive and negative self-tracking outcomes. In the case of a
      mixed-gain outcome profile, a spatially close (vs distant) presentation tended to
      increase the underestimation of the negative outcome (P=.06). In the case of a
      mixed-loss outcome profile, a spatially distant (vs close) presentation
      facilitated the exact recognition of the positive outcome (P=.04). When the
      presentation of self-tracking outcomes provided the opportunity for hedonic
      editing, users with a low (vs high) health motivation produced compensatory
      health beliefs, which led to lower health behavior intentions (index of moderated
      mediation=0.0352, 95% CI 0.0011-0.0923). CONCLUSIONS: When spatial distance
      between the presentations of mixed self-tracking outcomes provided the
      opportunity to hedonically edit one's self-tracking outcome profile, users
      recalled their self-tracking outcomes in a more positive light. Especially for
      users with lower health motivation, the opportunity to hedonically edit one's
      mixed self-tracking outcome profile led to reduced health behavior intentions. To
      prevent the occurrence of hedonic editing in users' responses to visually
      presented self-tracking outcome profiles, further research is necessary to
      determine the ideal distance that should be employed in the app design for the
      presentation of mixed self-tracking outcomes on a digital device's screen.

PMID- 29643052
TI  - The Effectiveness of Health Care Information Technologies: Evaluation of Trust,
      Security Beliefs, and Privacy as Determinants of Health Care Outcomes.
AB  - BACKGROUND: The diffusion of health information technologies (HITs) within the
      health care sector continues to grow. However, there is no theory explaining how
      success of HITs influences patient care outcomes. With the increase in data
      breaches, HITs' success now hinges on the effectiveness of data protection
      solutions. Still, empirical research has only addressed privacy concerns, with
      little regard for other factors of information assurance. OBJECTIVE: The
      objective of this study was to study the effectiveness of HITs using the DeLone
      and McLean Information Systems Success Model (DMISSM). We examined the role of
      information assurance constructs (ie, the role of information security beliefs,
      privacy concerns, and trust in health information) as measures of HIT
      effectiveness. We also investigated the relationships between information
      assurance and three aspects of system success: attitude toward health information
      exchange (HIE), patient access to health records, and perceived patient care
      quality. METHODS: Using structural equation modeling, we analyzed the data from a
      sample of 3677 cancer patients from a public dataset. We used R software (R
      Project for Statistical Computing) and the Lavaan package to test the
      hypothesized relationships. RESULTS: Our extension of the DMISSM to health care
      was supported. We found that increased privacy concerns reduce the frequency of
      patient access to health records use, positive attitudes toward HIE, and
      perceptions of patient care quality. Also, belief in the effectiveness of
      information security increases the frequency of patient access to health records
      and positive attitude toward HIE. Trust in health information had a positive
      association with attitudes toward HIE and perceived patient care quality. Trust
      in health information had no direct effect on patient access to health records;
      however, it had an indirect relationship through privacy concerns. CONCLUSIONS:
      Trust in health information and belief in the effectiveness of information
      security safeguards increases perceptions of patient care quality. Privacy
      concerns reduce patients' frequency of accessing health records, patients'
      positive attitudes toward HIE exchange, and overall perceived patient care
      quality. Health care organizations are encouraged to implement security
      safeguards to increase trust, the frequency of health record use, and reduce
      privacy concerns, consequently increasing patient care quality.

PMID- 29643053
TI  - A Novel Mobile App and Population Management System to Manage Rheumatoid
      Arthritis Flares: Protocol for a Randomized Controlled Trial.
AB  - BACKGROUND: Rheumatoid arthritis flares have a profound effect on patients,
      causing pain and disability. However, flares often occur between regularly
      scheduled health care provider visits and are, therefore, difficult to monitor
      and manage. We sought to develop a mobile phone app combined with a population
      management system to help track RA flares between visits. OBJECTIVE: The
      objective of this study is to implement the mobile app plus the population
      management system to monitor rheumatoid arthritis disease activity between
      scheduled health care provider visits over a period of 6 months. METHODS: This is
      a randomized controlled trial that lasts for 6 months for each participant. We
      aim to recruit 190 patients, randomized 50:50 to the intervention group versus
      the control group. The intervention group will be assigned the mobile app and be
      prompted to answer daily questionnaires sent to their mobile devices. Both groups
      will be assigned a population manager, who will communicate with the participants
      via telephone at 6 weeks and 18 weeks. The population manager will also
      communicate with the participants in the intervention group if their responses
      indicate a sustained increase in rheumatoid arthritis disease activity. To assess
      patient satisfaction, the primary outcomes will be scores on the Treatment
      Satisfaction Questionnaire for Medication as well as the Perceived Efficacy in
      Patient-Physician Interactions questionnaire at 6 months. To determine the effect
      of the mobile app on rheumatoid arthritis disease activity, the primary outcome
      will be the Clinical Disease Activity Index at 6 months. RESULTS: The trial
      started in November 2016, and an estimated 2.5 years will be necessary to
      complete the study. Study results are expected to be published by the end of
      2019. CONCLUSIONS: The completion of this study will provide important data
      regarding the following: (1) the assessment of validated outcome measures to
      assess rheumatoid arthritis disease activity with a mobile app between routinely
      scheduled health care provider visits, (2) patient engagement in monitoring their
      condition, and (3) communication between patients and health care providers
      through the population management system. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT02822521, http://clinicaltrials.gov/ct2/show/NCT02822521 (Archived by WebCite
      at http://www.webcitation.org/6xed3kGPd).

PMID- 29643054
TI  - Wearable Activity Tracker Use Among Australian Adolescents: Usability and
      Acceptability Study.
AB  - BACKGROUND: Wearable activity trackers have the potential to be integrated into
      physical activity interventions, yet little is known about how adolescents use
      these devices or perceive their acceptability. OBJECTIVE: The aim of this study
      was to examine the usability and acceptability of a wearable activity tracker
      among adolescents. A secondary aim was to determine adolescents' awareness and
      use of the different functions and features in the wearable activity tracker and
      accompanying app. METHODS: Sixty adolescents (aged 13-14 years) in year 8 from 3
      secondary schools in Melbourne, Australia, were provided with a wrist-worn Fitbit
      Flex and accompanying app, and were asked to use it for 6 weeks. Demographic data
      (age, sex) were collected via a Web-based survey completed during week 1 of the
      study. At the conclusion of the 6-week period, all adolescents participated in
      focus groups that explored their perceptions of the usability and acceptability
      of the Fitbit Flex, accompanying app, and Web-based Fitbit profile. Qualitative
      data were analyzed using pen profiles, which were constructed from verbatim
      transcripts. RESULTS: Adolescents typically found the Fitbit Flex easy to use for
      activity tracking, though greater difficulties were reported for monitoring
      sleep. The Fitbit Flex was perceived to be useful for tracking daily activities,
      and adolescents used a range of features and functions available through the
      device and the app. Barriers to use included the comfort and design of the Fitbit
      Flex, a lack of specific feedback about activity levels, and the inability to
      wear the wearable activity tracker for water-based sports. CONCLUSIONS:
      Adolescents reported that the Fitbit Flex was easy to use and that it was a
      useful tool for tracking daily activities. A number of functions and features
      were used, including the device's visual display to track and self-monitor
      activity, goal-setting in the accompanying app, and undertaking challenges
      against friends. However, several barriers to use were identified, which may
      impact on sustained use over time. Overall, wearable activity trackers have the
      potential to be integrated into physical activity interventions targeted at
      adolescents, but both the functionality and wearability of the monitor should be
      considered.

PMID- 29643055
TI  - Findings of the Chronic Obstructive Pulmonary Disease-Sitting and Exacerbations
      Trial (COPD-SEAT) in Reducing Sedentary Time Using Wearable and Mobile
      Technologies With Educational Support: Randomized Controlled Feasibility Trial.
AB  - BACKGROUND: Targeting sedentary time post exacerbation may be more relevant than
      targeting structured exercise for individuals with chronic obstructive pulmonary
      disease. Focusing interventions on sitting less and moving more after an
      exacerbation may act as a stepping stone to increase uptake to pulmonary
      rehabilitation. OBJECTIVE: The aim of this paper was to conduct a randomized
      trial examining trial feasibility and the acceptability of an education and self
      monitoring intervention using wearable technology to reduce sedentary behavior
      for individuals with chronic obstructive pulmonary disease admitted to hospital
      for an acute exacerbation. METHODS: Participants were recruited and randomized in
      hospital into 3 groups, with the intervention lasting 2 weeks post discharge. The
      Education group received verbal and written information about reducing their time
      in sedentary behavior, sitting face-to-face with a study researcher. The
      Education+Feedback group received the same education component along with real
      time feedback on their sitting time, stand-ups, and steps at home through a waist
      worn inclinometer linked to an app. Patients were shown how to use the technology
      by the same study researcher. The inclinometer also provided vibration prompts to
      encourage movement at patient-defined intervals of time. Patients and health care
      professionals involved in chronic obstructive pulmonary disease exacerbation care
      were interviewed to investigate trial feasibility and acceptability of trial
      design and methods. Main quantitative outcomes of trial feasibility were
      eligibility, uptake, and retention, and for acceptability, were behavioral
      responses to the vibration prompts. RESULTS: In total, 111 patients were
      approached with 33 patients recruited (11 Control, 10 Education, and 12
      Education+Feedback). Retention at 2-week follow-up was 52% (17/33; n=6 for
      Control, n=3 for Education, and n=8 for Education+Feedback). No study-related
      adverse events occurred. Collectively, patients responded to 106 out of 325
      vibration prompts from the waist-worn inclinometer (32.62%). Within 5 min of the
      prompt, 41% of responses occurred, with patients standing for a mean 1.4 (SD 0.8)
      min and walking for 0.4 (SD 0.3) min (21, SD 11, steps). Interviews indicated
      that being unwell and overwhelmed after an exacerbation was the main reason for
      not engaging with the intervention. Health care staff considered reducing
      sedentary behavior potentially attractive for patients but suggested starting the
      intervention as an inpatient. CONCLUSIONS: Although the data support that it was
      feasible to conduct the trial, modifications are needed to improve participant
      retention. The intervention was acceptable to most patients and health care
      professionals. TRIAL REGISTRATION: International Standard Randomized Controlled
      Trial Number (ISRCTN) 13790881; http://www.isrctn.com/ISRCTN13790881 (Archived by
      WebCite at http://www.webcitation.org/6xmnRGjFf).

PMID- 29643056
TI  - Mobile Breast Cancer e-Support Program for Chinese Women With Breast Cancer
      Undergoing Chemotherapy (Part 1): Qualitative Study of Women's Perceptions.
AB  - BACKGROUND: Women with breast cancer undergoing chemotherapy experience
      difficulty in accessing adequate cancer care in China. Mobile apps have the
      potential to provide easily accessible support for these women. However, there
      remains a paucity of randomized controlled trials to evaluate the effectiveness
      of app-based programs targeting specifically women with breast cancer undergoing
      chemotherapy. Moreover, women's perceptions and experiences related to using and
      interacting within the app-based program have rarely been reported. Therefore, an
      app-based Breast Cancer e-Support program was developed and evaluated using a
      randomized controlled trial. Based on the incorporation of Bandura's self
      efficacy and social exchange theory, Breast Cancer e-Support program lasted for
      12 weeks covering 4 cycles of chemotherapy and had 4 components: (1) a Learning
      forum, (2) a Discussion forum, (3) an Ask-the-Expert forum, and (4) a Personal
      Stories forum. OBJECTIVE: As a part of the randomized controlled trial, the aim
      of this study was to explore the participants' perception of Breast Cancer e
      Support program, its strengths and weaknesses, and suggestions to improve the
      program. METHODS: A descriptive qualitative study was employed. Thirteen women
      with breast cancer from 2 university-affiliated hospitals in China, who were
      randomly allocated to the Breast Cancer e-Support program in the randomized
      controlled trial, were interviewed from November 2016 to February 2017. Purposive
      sampling was used based on women's scores of self-efficacy after the completion
      of the intervention. Inductive content analysis was used to analyze the
      transcripts, allowing the categories and subcategories to flow from the data.
      RESULTS: The qualitative interviews revealed that participants perceived the
      Breast Cancer e-Support program to be helpful in enhancing knowledge, improving
      confidence level, and promoting emotional well-being. Women also identified
      access to tailored advice from experts and convenience as the benefits of this
      program. Physical or psychological health status, stigma related with breast
      cancer, and app instability were mentioned as the challenges to engagement.
      Suggestions for improvement included adding message reminders to prompt instant
      communication and search engine to locate information quickly, supplementing more
      interesting and practical knowledge, updating the information more often, and
      quickening the responses to women's questions. The participants recommended the
      Breast Cancer e-Support program to be incorporated as routine care to support
      women during chemotherapy. CONCLUSIONS: This study demonstrates the potential of
      the Breast Cancer e-Support program to support women during chemotherapy. Future
      app-based programs should apply a family-centered approach and provide more
      support on stigma associated with the disease to encourage engagement with the
      app. Suggestions of improvement regarding the design, content, and operation of
      the app-based intervention should be addressed in future studies. It is promising
      to incorporate the Breast Cancer e-Support program into routine care to
      generalize the benefits. TRIAL REGISTRATION: Australian New Zealand Clinical
      Trials Registry ACTRN12616000639426; http://www.ANZCTR.org.au/
      ACTRN12616000639426.aspx (Archived by WebCite at
      http://www.webcitation.org/6v1n9hGZq).

PMID- 29643058
TI  - Conceptual Framework for Addressing Residual Atherosclerotic Cardiovascular
      Disease Risk in the Era of Precision Medicine.

PMID- 29643057
TI  - Defective Base Excision Repair of Oxidative DNA Damage in Vascular Smooth Muscle
      Cells Promotes Atherosclerosis.
AB  - BACKGROUND: Atherosclerotic plaques demonstrate extensive accumulation of
      oxidative DNA damage, predominantly as 8-oxoguanine (8oxoG) lesions. 8oxoG is
      repaired by base excision repair enzymes; however, the mechanisms regulating
      8oxoG accumulation in vascular smooth muscle cells (VSMCs) and its effects on
      their function and in atherosclerosis are unknown. METHODS: We studied levels of
      8oxoG and its regulatory enzymes in human atherosclerosis, the mechanisms
      regulating 8oxoG repair and the base excision repair enzyme 8oxoG DNA glycosylase
      I (OGG1) in VSMCs in vitro, and the effects of reducing 8oxoG in VSMCs in
      atherosclerosis in ApoE-/- mice. RESULTS: Human plaque VSMCs showed defective
      nuclear 8oxoG repair, associated with reduced acetylation of OGG1. OGG1 was a key
      regulatory enzyme of 8oxoG repair in VSMCs, and its acetylation was crucial to
      its repair function through regulation of protein stability and expression. p300
      and sirtuin 1 were identified as the OGG1 acetyltransferase and deacetylase
      regulators, respectively, and both proteins interacted with OGG1 and regulated
      OGG1 acetylation at endogenous levels. However, p300 levels were decreased in
      human plaque VSMCs and in response to oxidative stress, suggesting that reactive
      oxygen species-induced regulation of OGG1 acetylation could be caused by reactive
      oxygen species-induced decrease in p300 expression. We generated mice that
      express VSMC-restricted OGG1 or an acetylation defective version (SM22alpha-OGG1
      and SM22alpha-OGG1K-R mice) and crossed them with ApoE-/- mice. We also studied
      ApoE-/- mice deficient in OGG1 (OGG1-/-). OGG1-/- mice showed increased 8oxoG in
      vivo and increased atherosclerosis, whereas mice expressing VSMC-specific OGG1
      but not the acetylation mutant OGG1K-R showed markedly reduced intracellular
      8oxoG and reduced atherosclerosis. VSMC OGG1 reduced telomere 8oxoG accumulation,
      DNA strand breaks, cell death and senescence after oxidant stress, and activation
      of proinflammatory pathways. CONCLUSIONS: We identify defective 8oxoG base
      excision repair in human atherosclerotic plaque VSMCs, OGG1 as a major 8oxoG
      repair enzyme in VSMCs, and p300/sirtuin 1 as major regulators of OGG1 through
      acetylation/deacetylation. Reducing oxidative damage by rescuing OGG1 activity
      reduces plaque development, indicating the detrimental effects of 8oxoG on VSMC
      function.

PMID- 29643059
TI  - Higher Collagen VI Formation Is Associated With All-Cause Mortality in Patients
      With Type 2 Diabetes and Microalbuminuria.
AB  - OBJECTIVE: Type 2 diabetes is a common risk factor for the development of chronic
      kidney disease (CKD). Enhanced de novo collagen type VI (COL VI) formation has
      been associated with renal fibrosis and CKD. We investigated the hypothesis that
      PRO-C6, a product specifically generated during COL VI formation, is prognostic
      for adverse outcomes in patients with type 2 diabetes and microalbuminuria.
      RESEARCH DESIGN AND METHODS: In a prospective, observational study, we measured
      PRO-C6 in the serum (S-PRO-C6) and urine (U-PRO-C6) of 198 patients with type 2
      diabetes and microalbuminuria without symptoms of coronary artery disease.
      Patients were followed for a median of 6.5 years, and end points were a composite
      of cardiovascular events (n = 38), all-cause mortality (n = 26), and reduction of
      estimated glomerular filtration rate (eGFR) of >30% (disease progression [n =
      42]). Cox models were unadjusted and adjusted for the conventional risk factors
      of sex, age, BMI, systolic blood pressure, LDL cholesterol, smoking, HbA1c,
      plasma creatinine, and urinary albumin excretion rate. RESULTS: Doubling of S-PRO
      C6 increased hazards for cardiovascular events (hazard ratio 3.06 [95% CI 1.31
      7.14]), all-cause mortality (6.91 [2.96-16.11]), and disease progression (4.81
      [1.92-12.01]). Addition of S-PRO-C6 to a model containing conventional risk
      factors improved relative integrated discrimination by 22.5% for cardiovascular
      events (P = 0.02), 76.8% for all-cause mortality (P = 0.002), and 53.3% for
      disease progression (P = 0.004). U-PRO-C6 was not significantly associated with
      any of the outcomes. CONCLUSIONS: S-PRO-C6 generated during COL VI formation
      predicts cardiovascular events, all-cause mortality, and disease progression in
      patients with type 2 diabetes and microalbuminuria.

PMID- 29643060
TI  - Use of Complementary and Alternative Medicine in Older Adults With Diabetes.

PMID- 29643061
TI  - Supplemental Oxygen Improves In Vivo Mitochondrial Oxidative Phosphorylation Flux
      in Sedentary Obese Adults With Type 2 Diabetes.
AB  - Type 2 diabetes is associated with impaired exercise capacity. Alterations in
      both muscle perfusion and mitochondrial function can contribute to exercise
      impairment. We hypothesized that impaired muscle mitochondrial function in type 2
      diabetes is mediated, in part, by decreased tissue oxygen delivery and would
      improve with oxygen supplementation. Ex vivo muscle mitochondrial content and
      respiration assessed from biopsy samples demonstrated expected differences in
      obese individuals with (n = 18) and without (n = 17) diabetes. Similarly, in vivo
      mitochondrial oxidative phosphorylation capacity measured in the gastrocnemius
      muscle via 31P-MRS indicated an impairment in the rate of ADP depletion with rest
      (27 +/- 6 s [diabetes], 21 +/- 7 s [control subjects]; P = 0.008) and oxidative
      phosphorylation (P = 0.046) in type 2 diabetes after isometric calf exercise
      compared with control subjects. Importantly, the in vivo impairment in oxidative
      capacity resolved with oxygen supplementation in adults with diabetes (ADP
      depletion rate 5.0 s faster, P = 0.012; oxidative phosphorylation 0.046 +/- 0.079
      mmol/L/s faster, P = 0.027). Multiple in vivo mitochondrial measures related to
      HbA1c These data suggest that oxygen availability is rate limiting for in vivo
      mitochondrial oxidative exercise recovery measured with 31P-MRS in individuals
      with uncomplicated diabetes. Targeting muscle oxygenation could improve exercise
      function in type 2 diabetes.

PMID- 29643062
TI  - A Survey on Data Reproducibility and the Effect of Publication Process on the
      Ethical Reporting of Laboratory Research.
AB  - Purpose: The successful translation of laboratory research into effective
      therapies is dependent upon the validity of peer-reviewed publications. However,
      several publications in recent years suggested that published scientific findings
      could be reproduced only 11% to 45% of the time. Multiple surveys attempted to
      elucidate the fundamental causes of data irreproducibility and underscored
      potential solutions, more robust experimental designs, better statistics, and
      better mentorship. However, no prior survey has addressed the role of the review
      and publication process on honest reporting.Experimental Design: We developed an
      anonymous online survey intended for trainees involved in bench research. The
      survey included questions related to mentoring/career development, research
      practice, integrity, and transparency, and how the pressure to publish and the
      publication process itself influence their reporting practices.Results: Responses
      to questions related to mentoring and training practices were largely positive,
      although an average of approximately 25% did not seem to receive optimal
      mentoring. A total of 39.2% revealed having been pressured by a principle
      investigator or collaborator to produce "positive" data. About 62.8% admitted
      that the pressure to publish influences the way they report data. The majority of
      respondents did not believe that extensive revisions significantly improved the
      manuscript while adding to the cost and time invested.Conclusions: This survey
      indicates that trainees believe that the pressure to publish affects honest
      reporting, mostly emanating from our system of rewards and advancement. The
      publication process itself affects faculty and trainees and appears to influence
      a shift in their ethics from honest reporting ("negative data") to selective
      reporting, data falsification, or even fabrication. Clin Cancer Res; 24(14); 3447
      55. (c)2018 AACR.

PMID- 29643063
TI  - Evaluation of Prexasertib, a Checkpoint Kinase 1 Inhibitor, in a Phase Ib Study
      of Patients with Squamous Cell Carcinoma.
AB  - Purpose: Prexasertib, a checkpoint kinase 1 inhibitor, demonstrated single-agent
      activity in patients with advanced squamous cell carcinoma (SCC) in the dose
      escalation portion of a phase I study (NCT01115790). Monotherapy prexasertib was
      further evaluated in patients with advanced SCC.Patients and Methods: Patients
      were given prexasertib 105 mg/m2 as a 1-hour infusion on day 1 of a 14-day cycle.
      Expansion cohorts were defined by tumor and treatment line. Safety, tolerability,
      efficacy, and exploratory biomarkers were analyzed.Results: Prexasertib was given
      to 101 patients, including 26 with SCC of the anus, 57 with SCC of the head and
      neck (SCCHN), and 16 with squamous cell non-small cell lung cancer (sqNSCLC).
      Patients were heavily pretreated (49% >=3 prior regimens). The most common
      treatment-related adverse event was grade 4 neutropenia (71%); 12% of patients
      had febrile neutropenia. Median progression-free survival was 2.8 months [90%
      confidence interval (CI), 1.9-4.2] for SCC of the anus, 1.6 months (90% CI, 1.4
      2.8) for SCCHN, and 3.0 months (90% CI, 1.4-3.9) for sqNSCLC. The clinical
      benefit rate at 3 months (complete response + partial response + stable disease)
      across tumors was 29% (23% SCC of the anus, 28% SCCHN, 44% sqNSCLC). Four
      patients with SCC of the anus had partial or complete response [overall response
      rate (ORR) = 15%], and three patients with SCCHN had partial response (ORR = 5%).
      Biomarker analyses focused on genes that altered DNA damage response or increased
      replication stress.Conclusions: Prexasertib demonstrated an acceptable safety
      profile and single-agent activity in patients with advanced SCC. The prexasertib
      maximum-tolerated dose of 105 mg/m2 was confirmed as the recommended phase II
      dose. Clin Cancer Res; 24(14); 3263-72. (c)2018 AACR.

PMID- 29643064
TI  - Racial Heterogeneity in Treatment Effects in Peripheral Artery Disease: Insights
      From the CLEVER Trial (Claudication: Exercise Versus Endoluminal
      Revascularization).

PMID- 29643066
TI  - Early Ambulation Among Hospitalized Heart Failure Patients Is Associated With
      Reduced Length of Stay and 30-Day Readmissions.
AB  - BACKGROUND: Early ambulation (EA) is associated with improved outcomes for
      mechanically ventilated and stroke patients. Whether the same association exists
      for patients hospitalized with acute heart failure is unknown. We sought to
      determine whether EA among patients hospitalized with heart failure is associated
      with length of stay, discharge disposition, 30-day post discharge readmissions,
      and mortality. METHODS AND RESULTS: The study population included 369 hospitals
      and 285 653 patients with heart failure enrolled in the Get With The Guidelines
      Heart Failure registry. We used multivariate logistic regression with generalized
      estimating equations at the hospital level to identify predictors of EA and
      determine the association between EA and outcomes. Sixty-five percent of patients
      ambulated by day 2 of the hospital admission. Patient-level predictors of EA
      included younger age, male sex, and hospitalization outside of the Northeast
      (P<0.01 for all). Hospital size and academic status were not predictive. Hospital
      level analysis revealed that those hospitals with EA rates in the top 25% were
      less likely to have a long length of stay (defined as >4 days) compared with
      those in the bottom 25% (odds ratio, 0.83; confidence interval, 0.73-0.94;
      P=0.004). Among a subgroup of fee-for-service Medicare beneficiaries, we found
      that hospitals in the highest quartile of rates of EA demonstrated a
      statistically significant 24% lower 30-day readmission rates (P<0.0001). Both end
      points demonstrated a dose-response association and statistically significant P
      for trend test. CONCLUSIONS: Multivariable-adjusted hospital-level analysis
      suggests an association between EA and both shorter length of stay and lower 30
      day readmissions. Further prospective studies are needed to validate these
      findings.

PMID- 29643065
TI  - Pulmonary Effective Arterial Elastance as a Measure of Right Ventricular
      Afterload and Its Prognostic Value in Pulmonary Hypertension Due to Left Heart
      Disease.
AB  - BACKGROUND: Patients with combined post- and precapillary pulmonary hypertension
      due to left heart disease have a worse prognosis compared with isolated
      postcapillary. However, it remains unclear whether increased mortality in
      combined post- and precapillary pulmonary hypertension is simply a result of
      higher total right ventricular load. Pulmonary effective arterial elastance (Ea)
      is a measure of total right ventricular afterload, reflecting both resistive and
      pulsatile components. We aimed to test whether pulmonary Ea discriminates
      survivors from nonsurvivors in patients with pulmonary hypertension due to left
      heart disease and if it does so better than other hemodynamic parameters
      associated with combined post- and precapillary pulmonary hypertension. METHODS
      AND RESULTS: We combined 3 large heart failure patient cohorts (n=1036) from
      academic hospitals, including patients with pulmonary hypertension due to heart
      failure with preserved ejection fraction (n=232), reduced ejection fraction
      (n=335), and a mixed population (n=469). In unadjusted and 2 adjusted models,
      pulmonary Ea more robustly predicted mortality than pulmonary vascular resistance
      and the transpulmonary gradient. Along with pulmonary arterial compliance,
      pulmonary Ea remained predictive of survival in patients with normal pulmonary
      vascular resistance. The diastolic pulmonary gradient did not predict mortality.
      In addition, in a subset of patients with echocardiographic data, Ea and
      pulmonary arterial compliance were better discriminators of right ventricular
      dysfunction than the other parameters. CONCLUSIONS: Pulmonary Ea and pulmonary
      arterial compliance more consistently predicted mortality than pulmonary vascular
      resistance or transpulmonary gradient across a spectrum of left heart disease
      with pulmonary hypertension, including patients with heart failure with preserved
      ejection fraction, heart failure with reduced ejection fraction, and pulmonary
      hypertension with a normal pulmonary vascular resistance.

PMID- 29643067
TI  - Incidence, Predictors, and Outcomes Associated With Hypotensive Episodes Among
      Heart Failure Patients Receiving Sacubitril/Valsartan or Enalapril: The PARADIGM
      HF Trial (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor
      With Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global
      Mortality and Morbidity in Heart Failure).
AB  - BACKGROUND: In PARADIGM-HF (Prospective Comparison of Angiotensin Receptor
      Neprilysin Inhibitor With Angiotensin-Converting Enzyme Inhibitor to Determine
      Impact on Global Mortality and Morbidity in Heart Failure), heart failure
      treatment with sacubitril/valsartan reduced the primary composite outcome of
      cardiovascular death or heart failure hospitalization compared with enalapril but
      resulted in more symptomatic hypotension. Concern on hypotension may be limiting
      use of sacubitril/valsartan in appropriate patients. METHODS AND RESULTS: We
      characterized patients in PARADIGM-HF by whether they reported hypotension during
      study run-in periods (enalapril, followed by sacubitril/valsartan) and after
      randomization and assessed whether hypotension modified the efficacy of
      sacubitril/valsartan. Of the 10 513 patients entering the enalapril run-in, 136
      (1.3%) experienced hypotension and 93 (68%) were unable to continue to the next
      phase; of 9419 patients entering the sacubitril/valsartan run-in period, 228
      (2.4%) patients experienced hypotension and 51% were unable to successfully
      complete the run-in. After randomization, 388 (9.2%) participants had 501
      hypotensive events with enalapril, and 588 (14.0%) participants had 803
      hypotensive events with sacubitril/valsartan (P<0.001). There was no difference
      between randomized treatment groups in the number of participants who
      discontinued therapy because of hypotension. Individuals with a hypotensive event
      in either group were older, had lower blood pressure at randomization, and were
      more likely to have an implantable cardioverter defibrillator. Participants with
      hypotensive events during run-in who were ultimately randomized derived similar
      efficacy from sacubitril/valsartan compared with enalapril as those without
      hypotensive events (P interaction>0.90). CONCLUSIONS: Hypotension was more common
      with sacubitril/valsartan relative to enalapril in PARADIGM-HF but did not
      differentially affect permanent discontinuations. Patients with hypotension
      during run-in derived similar benefit from sacubitril/valsartan compared with
      enalapril as those who did not experience hypotension.

PMID- 29643068
TI  - Hydrogen peroxide is a neuronal alarmin that triggers specific RNAs, local
      translation of Annexin A2, and cytoskeletal remodeling in Schwann cells.
AB  - Schwann cells are key players in neuro-regeneration: They sense "alarm" signals
      released by degenerating nerve terminals and differentiate toward a
      proregenerative phenotype, with phagocytosis of nerve debris and nerve guidance.
      At the murine neuromuscular junction, hydrogen peroxide (H2O2) is a key signal of
      Schwann cells' activation in response to a variety of nerve injuries. Here we
      report that Schwann cells exposed to low doses of H2O2 rewire the expression of
      several RNAs at both transcriptional and translational levels. Among the genes
      positively regulated at both levels, we identified an enriched cluster involved
      in cytoskeleton remodeling and cell migration, with the Annexin (Anxa) proteins
      being the most represented family. We show that both Annexin A2 (Anxa2)
      transcript and protein accumulate at the tips of long pseudopods that Schwann
      cells extend upon H2O2 exposure. Interestingly, Schwann cells reply to this
      signal and to nerve injury by locally translating Anxa2 in pseudopods, and
      undergo an extensive cytoskeleton remodeling. Our results show that, similarly to
      neurons, Schwann cells take advantage of local protein synthesis to change shape
      and move toward damaged axonal terminals to facilitate axonal regeneration.

PMID- 29643070
TI  - Neurobehavioral Outcomes 11 Years After Neonatal Caffeine Therapy for Apnea of
      Prematurity.
AB  - BACKGROUND AND OBJECTIVES: Caffeine is effective in the treatment of apnea of
      prematurity. Although caffeine therapy has a benefit on gross motor skills in
      school-aged children, effects on neurobehavioral outcomes are not fully
      understood. We aimed to investigate effects of neonatal caffeine therapy in very
      low birth weight (500-1250 g) infants on neurobehavioral outcomes in 11-year-old
      participants of the Caffeine for Apnea of Prematurity trial. METHODS: Thirteen
      academic hospitals in Canada, Australia, Great Britain, and Sweden participated
      in this part of the 11-year follow-up of the double-blind, randomized, placebo
      controlled trial. Measures of general intelligence, attention, executive
      function, visuomotor integration and perception, and behavior were obtained in up
      to 870 children. The effects of caffeine therapy were assessed by using
      regression models. RESULTS: Neurobehavioral outcomes were generally similar for
      both the caffeine and placebo group. The caffeine group performed better than the
      placebo group in fine motor coordination (mean difference [MD] = 2.9; 95%
      confidence interval [CI]: 0.7 to 5.1; P = .01), visuomotor integration (MD = 1.8;
      95% CI: 0.0 to 3.7; P < .05), visual perception (MD = 2.0; 95% CI: 0.3 to 3.8; P
      = .02), and visuospatial organization (MD = 1.2; 95% CI: 0.4 to 2.0; P = .003).
      CONCLUSIONS: Neonatal caffeine therapy for apnea of prematurity improved
      visuomotor, visuoperceptual, and visuospatial abilities at age 11 years. General
      intelligence, attention, and behavior were not adversely affected by caffeine,
      which highlights the long-term safety of caffeine therapy for apnea of
      prematurity in very low birth weight neonates.

PMID- 29643069
TI  - An m6A-YTH Module Controls Developmental Timing and Morphogenesis in Arabidopsis.
AB  - Methylation of N6-adenosine (m6A) in mRNA is an important posttranscriptional
      gene regulatory mechanism in eukaryotes. m6A provides a binding site for effector
      proteins ("readers") that influence pre-mRNA splicing, mRNA degradation, or
      translational efficiency. YT521-B homology (YTH) domain proteins are important
      m6A readers with established functions in animals. Plants contain more YTH domain
      proteins than other eukaryotes, but their biological importance remains unknown.
      Here, we show that the cytoplasmic Arabidopsis thaliana YTH domain proteins
      EVOLUTIONARILY CONSERVED C-TERMINAL REGION2/3 (ECT2/3) are required for the
      correct timing of leaf formation and for normal leaf morphology. These functions
      depend fully on intact m6A binding sites of ECT2 and ECT3, indicating that they
      function as m6A readers. Mutation of the close ECT2 homolog, ECT4, enhances the
      delayed leaf emergence and leaf morphology defects of ect2/ect3 mutants, and all
      three ECT proteins are expressed at leaf formation sites in the shoot apex of
      young seedlings and in the division zone of developing leaves. ECT2 and ECT3 are
      also highly expressed at early stages of trichome development and are required
      for trichome morphology, as previously reported for m6A itself. Overall, our
      study establishes the relevance of a cytoplasmic m6A-YTH regulatory module in the
      timing and execution of plant organogenesis.

PMID- 29643071
TI  - Facilitating the Timely Discharge of Well Newborns by Using Quality Improvement
      Methods.
AB  - BACKGROUND AND OBJECTIVES: Discharges are a key driver of hospital throughput.
      Our pediatric hospitalist team sought to improve newborn nursery throughput by
      increasing the percentage of newborns on our service with a discharge order by 11
      am. We hypothesized that implementing a discharge checklist would result in
      earlier discharge times for newborns who met discharge criteria. METHODS: We
      identified barriers to timely discharge through focus groups with key
      stakeholders, chart reviews, and brainstorming sessions. We subsequently created
      and implemented a discharge checklist to identify and address barriers before
      daily rounds. We tracked mean monthly discharge order times. Finally, we
      performed chart reviews to determine causes for significantly delayed discharge
      orders and used this information to modify rounding practices during a second
      plan-do-study-act cycle. RESULTS: During the 2-year period before the
      intervention, 24% of 3224 newborns had a discharge order entered by 11 am. In the
      20 months after the intervention, 39% of 2739 newborns had a discharge order by
      11 am, a 63% increase compared with the baseline. Observation for group B
      Streptococcus exposure was the most frequent reason for a late discharge order.
      CONCLUSIONS: There are many factors that affect the timely discharge of well
      newborns. The development and implementation of a discharge checklist improved
      our ability to discharge newborns on our pediatric hospitalist service by 11 am.
      Future studies to identify nonphysician barriers to timely newborn discharges may
      lead to further improvements in throughput between the labor and delivery and
      maternity suites units.

PMID- 29643072
TI  - Life history variation is maintained by fitness trade-offs and negative frequency
      dependent selection.
AB  - The maintenance of diverse life history strategies within and among species
      remains a fundamental question in ecology and evolutionary biology. By using a
      near-complete 16-year pedigree of 12,579 winter-run steelhead (Oncorhynchus
      mykiss) from the Hood River, Oregon, we examined the continued maintenance of two
      life history traits: the number of lifetime spawning events (semelparous vs.
      iteroparous) and age at first spawning (2-5 years). We found that repeat-spawning
      fish had more than 2.5 times the lifetime reproductive success of single-spawning
      fish. However, first-time repeat-spawning fish had significantly lower
      reproductive success than single-spawning fish of the same age, suggesting that
      repeat-spawning fish forego early reproduction to devote additional energy to
      continued survival. For single-spawning fish, we also found evidence for a
      fitness trade-off for age at spawning: older, larger males had higher
      reproductive success than younger, smaller males. For females, in contrast, we
      found that 3-year-old fish had the highest mean lifetime reproductive success
      despite the observation that 4- and 5-year-old fish were both longer and heavier.
      This phenomenon was explained by negative frequency-dependent selection: as 4-
      and 5-year-old fish decreased in frequency on the spawning grounds, their
      lifetime reproductive success became greater than that of the 3-year-old fish.
      Using a combination of mathematical and individual-based models parameterized
      with our empirical estimates, we demonstrate that both fitness trade-offs and
      negative frequency-dependent selection observed in the empirical data can
      theoretically maintain the diverse life history strategies found in this
      population.

PMID- 29643073
TI  - The plant hormone ethylene restricts Arabidopsis growth via the epidermis.
AB  - The gaseous hormone ethylene plays a key role in plant growth and development,
      and it is a major regulator of stress responses. It inhibits vegetative growth by
      restricting cell elongation, mainly through cross-talk with auxins. However, it
      remains unknown whether ethylene controls growth throughout all plant tissues or
      whether its signaling is confined to specific cell types. We employed a targeted
      expression approach to map the tissue site(s) of ethylene growth regulation. The
      ubiquitin E3 ligase complex containing Skp1, Cullin1, and the F-box protein EBF1
      or EBF2 (SCFEBF1/2) target the degradation of EIN3, the master transcription
      factor in ethylene signaling. We coupled EBF1 and EBF2 to a number of cell type
      specific promoters. Using phenotypic assays for ethylene response and mutant
      complementation, we revealed that the epidermis is the main site of ethylene
      action controlling plant growth in both roots and shoots. Suppression of ethylene
      signaling in the epidermis of the constitutive ethylene signaling mutant ctr1-1
      was sufficient to rescue the mutant phenotype, pointing to the epidermis as a key
      cell type required for ethylene-mediated growth inhibition.

PMID- 29643074
TI  - Nucleus-specific expression in the multinuclear mushroom-forming fungus Agaricus
      bisporus reveals different nuclear regulatory programs.
AB  - Many fungi are polykaryotic, containing multiple nuclei per cell. In the case of
      heterokaryons, there are different nuclear types within a single cell. It is
      unknown what the different nuclear types contribute in terms of mRNA expression
      levels in fungal heterokaryons. Each cell of the mushroom Agaricus bisporus
      contains two to 25 nuclei of two nuclear types originating from two parental
      strains. Using RNA-sequencing data, we assess the differential mRNA contribution
      of individual nuclear types and its functional impact. We studied differential
      expression between genes of the two nuclear types, P1 and P2, throughout mushroom
      development in various tissue types. P1 and P2 produced specific mRNA profiles
      that changed through mushroom development. Differential regulation occurred at
      the gene level, rather than at the locus, chromosomal, or nuclear level. P1
      dominated mRNA production throughout development, and P2 showed more
      differentially up-regulated genes in important functional groups. In the
      vegetative mycelium, P2 up-regulated almost threefold more metabolism genes and
      carbohydrate active enzymes (cazymes) than P1, suggesting phenotypic differences
      in growth. We identified widespread transcriptomic variation between the nuclear
      types of A. bisporus Our method enables studying nucleus-specific expression,
      which likely influences the phenotype of a fungus in a polykaryotic stage. Our
      findings have a wider impact to better understand gene regulation in fungi in a
      heterokaryotic state. This work provides insight into the transcriptomic
      variation introduced by genomic nuclear separation.

PMID- 29643075
TI  - Widespread changes in transcriptome profile of human mesenchymal stem cells
      induced by two-dimensional nanosilicates.
AB  - Two-dimensional nanomaterials, an ultrathin class of materials such as graphene,
      nanoclays, transition metal dichalcogenides (TMDs), and transition metal oxides
      (TMOs), have emerged as a new generation of materials due to their unique
      properties relative to macroscale counterparts. However, little is known about
      the transcriptome dynamics following exposure to these nanomaterials. Here, we
      investigate the interactions of 2D nanosilicates, a layered clay, with human
      mesenchymal stem cells (hMSCs) at the whole-transcriptome level by high
      throughput sequencing (RNA-seq). Analysis of cell-nanosilicate interactions by
      monitoring changes in transcriptome profile uncovered key biophysical and
      biochemical cellular pathways triggered by nanosilicates. A widespread alteration
      of genes was observed due to nanosilicate exposure as more than 4,000 genes were
      differentially expressed. The change in mRNA expression levels revealed clathrin
      mediated endocytosis of nanosilicates. Nanosilicate attachment to the cell
      membrane and subsequent cellular internalization activated stress-responsive
      pathways such as mitogen-activated protein kinase (MAPK), which subsequently
      directed hMSC differentiation toward osteogenic and chondrogenic lineages. This
      study provides transcriptomic insight on the role of surface-mediated cellular
      signaling triggered by nanomaterials and enables development of nanomaterials
      based therapeutics for regenerative medicine. This approach in understanding
      nanomaterial-cell interactions illustrates how change in transcriptomic profile
      can predict downstream effects following nanomaterial treatment.

PMID- 29643076
TI  - High Salt Cross-Protects Escherichia coli from Antibiotic Treatment through
      Increasing Efflux Pump Expression.
AB  - Environmental stresses often co-occur when bacteria encounter antibiotic
      treatment inside the human body. The cellular response to environmental stressors
      can alter the global gene expression pattern of bacteria. However, the
      relationship between the cellular stress response and antibiotic susceptibility
      remains poorly understood. Here we studied the effect of high salt, an important
      environmental stress condition inside the human body, on bacterial susceptibility
      to antibiotics. We found that high salt reduces the susceptibility of Escherichia
      coli to tetracycline and chloramphenicol, leading to a cross-protection effect.
      The cross-protection effect originates from the increased AcrAB-TolC efflux pump
      expression level under high-salt conditions. Our study demonstrates that stress
      induced gene expression alterations can cross-protect bacteria from antibiotic
      treatment and should thus be considered when investigating antibiotic
      susceptibility and applying antimicrobial treatment.IMPORTANCE Environmental
      stresses often co-occur when bacteria confront antibiotic treatment. We provide a
      clear example that a natural stress condition (high salt) can cross-protect
      bacteria from antibiotic treatment by triggering the bacterial stress response
      program (elevated AcrAB-TolC efflux pump expression). Our study highlights the
      importance of taking the co-occurrence of bacterial environmental stresses into
      consideration when investigating antibiotic susceptibility and applying
      antimicrobial treatment.

PMID- 29643077
TI  - Single-Cell Analysis Reveals Distinct Gene Expression and Heterogeneity in Male
      and Female Plasmodium falciparum Gametocytes.
AB  - Sexual reproduction is an obligate step in the Plasmodium falciparum life cycle,
      with mature gametocytes being the only form of the parasite capable of human-to
      mosquito transmission. Development of male and female gametocytes takes 9 to 12
      days, and although more than 300 genes are thought to be specific to gametocytes,
      only a few have been postulated to be male or female specific. Because these
      genes are often expressed during late gametocyte stages and for some, male- or
      female-specific transcript expression is debated, the separation of male and
      female populations is technically challenging. To overcome these challenges, we
      have developed an unbiased single-cell approach to determine which transcripts
      are expressed in male versus female gametocytes. Using microfluidic technology,
      we isolated single mid- to late-stage gametocytes to compare the expression of 91
      genes, including 87 gametocyte-specific genes, in 90 cells. Such analysis
      identified distinct gene clusters whose expression was associated with male,
      female, or all gametocytes. In addition, a small number of male gametocytes
      clustered separately from female gametocytes based on sex-specific expression
      independent of stage. Many female-enriched genes also exhibited stage-specific
      expression. RNA fluorescent in situ hybridization of male and female markers
      validated the mutually exclusive expression pattern of male and female
      transcripts in gametocytes. These analyses uncovered novel male and female
      markers that are expressed as early as stage III gametocytogenesis, providing
      further insight into Plasmodium sex-specific differentiation previously masked in
      population analyses. Our single-cell approach reveals the most robust markers for
      sex-specific differentiation in Plasmodium gametocytes. Such single-cell
      expression assays can be generalized to all eukaryotic pathogens.IMPORTANCE Most
      human deaths that result from malaria are caused by the eukaryotic parasite
      Plasmodium falciparum The only form of this parasite that is transmitted to the
      mosquito is the sexual form, called the gametocyte. The production of mature
      gametocytes can take up to 2 weeks and results in phenotypically distinct males
      and females, although what causes this gender-specific differentiation remains
      largely unknown. Here, we demonstrate the first use of microfluidic technology to
      capture single gametocytes and determine their temporal sex-specific gene
      expression in an unbiased manner. We were able to determine male or female
      identity of single cells based on the upregulation of gender-specific genes as
      early as mid-stage gametocytes. This analysis has revealed strong markers for
      male and female gametocyte differentiation that were previously concealed in
      population analyses. Similar single-cell analyses in eukaryotic pathogens using
      this method may uncover rare cell types and heterogeneity previously masked in
      population studies.

PMID- 29643078
TI  - Ehrlichia chaffeensis TRP75 Interacts with Host Cell Targets Involved in
      Homeostasis, Cytoskeleton Organization, and Apoptosis Regulation To Promote
      Infection.
AB  - Ehrlichia chaffeensis is an obligately intracellular bacterium that exhibits
      tropism for mononuclear phagocytes. The mechanisms involved in E. chaffeensis
      infection of the host cell and evasion of host defenses are not fully defined,
      but a subset of type 1 secreted tandem repeat protein (TRP) effectors play
      important roles. Recently, we determined molecular interactions of TRP120, TRP47,
      and TRP32 with the eukaryotic host cell. In this investigation, we used yeast two
      hybrid analysis to reveal that another E. chaffeensis tandem repeat protein,
      TRP75, interacts with a diverse group of human proteins associated with
      organismal and tissue homeostasis, multiple metabolic processes and regulation,
      response to reactive oxygen species, signal transduction, and protein
      modifications. Thirteen identified host target proteins associated with actin
      cytoskeleton reorganization or apoptosis were examined in detail and confirmed to
      interact with TRP75 at different levels as determined by coimmunoprecipitation
      assays. These protein interactions were visualized by immunofluorescence confocal
      microscopy during infection and colocalized with Ehrlichia morulae with different
      intensities. Moreover, small interfering RNAs (siRNAs) (n = 86) were used to
      knock down identified TRP75-interacting host proteins separately, and their
      influence on ehrlichial infection was investigated by real-time quantitative PCR
      (qPCR). Knockdown of 74/86 (86%) TRP75 target proteins had a significant negative
      effect on ehrlichial infection. The results of this study further support the
      idea of a role of Ehrlichia TRPs as effectors that interact with a complex array
      of host proteins to promote ehrlichial infection.IMPORTANCE Human monocytic
      ehrlichiosis (HME) is caused by an obligatory intracellular bacterium, E.
      chaffeensis, and is one of the most prevalent, life-threatening emerging
      infectious zoonoses in the United States. The mechanisms through which E.
      chaffeensis invades and establishes an intracellular niche are not well
      understood but are dependent on secreted ehrlichial effector proteins. The
      significance of this study is in addressing how intracellular pathogens,
      particularly those with small genomes such as Ehrlichia, exploit a limited number
      of secreted effector proteins such as tandem repeat proteins (TRPs) to manipulate
      complex eukaryotes and to regulate host cell processes through molecular pathogen
      host interplay. The results of our studies highlight the broader role of
      ehrlichial TRPs in promoting infection and help define the mechanisms through
      which obligately intracellular bacteria modulate host cell function for survival.

PMID- 29643079
TI  - Age at menopause and lifetime cognition: Findings from a British birth cohort
      study.
AB  - OBJECTIVE: We investigated whether cognitive performance between ages 43 and 69
      years was associated with timing of menopause, controlling for hormone
      replacement therapy, childhood cognitive ability, and sociobehavioral factors.
      METHODS: We used data from 1,315 women participating in the Medical Research
      Council National Survey of Health and Development (a British birth cohort study)
      with known age at period cessation and up to 4 assessments of verbal memory (word
      learning task) and processing speed (letter-cancellation task) at ages 43, 53, 60
      64, and 69. We fitted multilevel models with linear and quadratic age terms,
      stratified by natural or surgical menopause, and adjusted for hormone replacement
      therapy, body mass index, smoking, occupational class, education, and childhood
      cognitive ability. RESULTS: Verbal memory increased with later age at natural
      menopause (0.17 words per year, 95% confidence interval [CI]: 0.07-0.27, p =
      0.001); an association remained, albeit attenuated, after full adjustment (0.09,
      95% CI: 0.02-0.17, p = 0.013). Verbal memory also increased with later age at
      surgical menopause (0.16, 95% CI: 0.06-0.27, p = 0.002), but this association was
      fully attenuated after adjustment. Search speed was not associated with age at
      menopause. CONCLUSION: Our findings suggest lifelong hormonal processes, not just
      short-term fluctuations during the menopause transition, may be associated with
      verbal memory, consistent with evidence from a variety of neurobiological
      studies; mechanisms are likely to involve estrogen receptor beta function.
      Further follow-up is required to assess fully the clinical significance of these
      associations.

PMID- 29643082
TI  - Updating Neurology(r) authorship criteria: Ensuring inclusion of those making
      valuable intellectual contributions.

PMID- 29643080
TI  - Periodic limb movements during sleep in stroke/TIA: Prevalence, course, and
      cardiovascular burden.
AB  - OBJECTIVE: To define the prevalence, time course, and associated factors of
      periodic limb movements during sleep (PLMS) in patients with ischemic stroke or
      TIA. METHODS: Patients enrolled in the prospective Sleep-Disordered Breathing in
      Transient Ischemia Attack (TIA)/Ischemic Stroke and Continuous Positive Airway
      Pressure (CPAP) Treatment Efficacy (SAS-CARE) study underwent a double
      polysomnographic investigation in the acute and chronic phases after stroke/TIA,
      together with a MRI brain scan and a 24-hour blood pressure evaluation. The
      prevalence of PLMS in patients was compared with that in a matched sample of
      randomly selected healthy controls from the HypnoLaus cohort. One hundred sixty
      nine recordings were performed in the acute phase and 191 after 3 months (210
      recordings were obtained from the same 105 patients in both phases) and were
      compared to those of 162 controls. RESULTS: The mean number of PLMS per hour and
      the percentage of participants with a PLMS index >10 and >15 per hour were
      similar between patients and controls. PLMS remained stable from the acute to the
      chronic phase after stroke. Factors positively associated with PLMS were age,
      body mass index, and history of hypertension. Blood pressure over 24 hours and
      the burden of cerebrovascular damage were similar between the groups with PLMS
      and without PLMS. CONCLUSIONS: PLMS are equally frequent in patients with
      stroke/TIA and the general population. The absence of higher blood pressure
      values and of a greater vascular brain damage found in patients with PLMS
      compared to those without PLMS might be due to a greater use of antihypertensive
      medication among patients with PLMS, which corresponds to a higher prevalence of
      previous diagnosis of hypertension in these patients.

PMID- 29643081
TI  - Integration of risk factors for Parkinson disease in 2 large longitudinal
      cohorts.
AB  - OBJECTIVE: To prospectively examine how selected lifestyle factors and family
      history of Parkinson disease (PD) combine to determine overall PD risk. METHODS:
      We derived risk scores among 69,968 women in the Nurses' Health Study (NHS) (1984
      2012) and 45,830 men in the Health Professionals Follow-up Study (HPFS) (1986
      2012). Risk scores were computed for each individual based on the following
      factors previously associated with PD risk: total caffeine intake, smoking,
      physical activity, and family history of PD for the NHS, and additionally total
      flavonoid intake and dietary urate index for the HPFS. Hazard ratios were
      estimated using Cox proportional hazards models. In addition, we performed tests
      of interactions on both the multiplicative and additive scale between pairs of
      risk factors. RESULTS: We documented 1,117 incident PD cases during follow-up.
      The adjusted hazard ratios comparing individuals in the highest category of the
      reduced risk score to those in the lowest category were 0.33 (95% confidence
      interval: 0.21, 0.49; ptrend < 0.0001) in the NHS and 0.18 (95% confidence
      interval: 0.10, 0.32; ptrend < 0.0001) in the HPFS. Results were similar when
      applying the risk scores computed by summing the predictors weighted by the log
      of their individual effect sizes on PD risk in these cohorts. Additive
      interaction was present between no family history of PD and caffeine in men and
      between caffeine and physical activity in women. CONCLUSIONS: Our results suggest
      that known protective factors for PD tend to have additive or superadditive
      effects, so that PD risk is very low in individuals with multiple protective risk
      factors.

PMID- 29643083
TI  - HeadPoST: Rightly positioned, or flat out wrong?
AB  - OBJECTIVE: To critique the Head Positioning in Stroke Trial (HeadPoST) study
      methods in relation to preceding research findings in an aim to clarify the
      potential efficacy of positioning interventions and direction for future
      research. METHODS: Head positioning research prior to the conduct of HeadPoST was
      reviewed by a team of international stroke experts, and methods and findings were
      compared to HeadPoST. RESULTS: Methods used to select HeadPoST patients differ
      substantially from those used in original head positioning studies, in particular
      enrollment of all types of stroke. HeadPoST enrolled primarily minor strokes
      (median NIH Stroke Scale 4, interquartile range [IQR] 2-8) without vascular
      imaging confirmation of subtype; elapsed time from stroke symptom onset to the
      initiation of intervention was late (median 14 hours, IQR 5-35), and time from
      hospital admission to enrollment was delayed (median 7 hours, IQR 2-26).
      Intervention integrity was not reported, including ability to achieve/maintain 30
      degrees  head elevation in beds lacking head elevation capabilities.
      Deterioration or improvement associated with the intervention is unknown as
      serial assessments were not completed, and the trial's 3-month outcome was
      powered using unrelated study data. CONCLUSIONS: The design of HeadPoST was
      suboptimal to measure differences produced by the intervention. Future head
      positioning trials in discrete patient cohorts (in particular, large vessel
      occlusion) with endpoints supported by pilot work are required to understand the
      efficacy of this simple yet potentially important intervention.

PMID- 29643085
TI  - Hundreds more doctors from overseas are applying to work in the UK.

PMID- 29643086
TI  - Better patient flow in cardiac and thoracic surgery could save L45m a year in
      England.

PMID- 29643088
TI  - The "greener grass" of a consultant post looks like a tired lawn.

PMID- 29643084
TI  - Factors associated with treatment delays in pediatric refractory convulsive
      status epilepticus.
AB  - OBJECTIVE: To identify factors associated with treatment delays in pediatric
      patients with convulsive refractory status epilepticus (rSE). METHODS: This
      prospective, observational study was performed from June 2011 to March 2017 on
      pediatric patients (1 month to 21 years of age) with rSE. We evaluated potential
      factors associated with increased treatment delays in a Cox proportional hazards
      model. RESULTS: We studied 219 patients (53% males) with a median (25th-75th
      percentiles [p25-p75]) age of 3.9 (1.2-9.5) years in whom rSE started out of
      hospital (141 [64.4%]) or in hospital (78 [35.6%]). The median (p25-p75) time
      from seizure onset to treatment was 16 (5-45) minutes to first benzodiazepine
      (BZD), 63 (33-146) minutes to first non-BZD antiepileptic drug (AED), and 170
      (107-539) minutes to first continuous infusion. Factors associated with more
      delays to administration of the first BZD were intermittent rSE (hazard ratio
      [HR] 1.54, 95% confidence interval [CI] 1.14-2.09; p = 0.0467) and out-of
      hospital rSE onset (HR 1.5, 95% CI 1.11-2.04; p = 0.0467). Factors associated
      with more delays to administration of the first non-BZD AED were intermittent rSE
      (HR 1.78, 95% CI 1.32-2.4; p = 0.001) and out-of-hospital rSE onset (HR 2.25, 95%
      CI 1.67-3.02; p < 0.0001). None of the studied factors were associated with a
      delayed administration of continuous infusion. CONCLUSION: Intermittent rSE and
      out-of-hospital rSE onset are independently associated with longer delays to
      administration of the first BZD and the first non-BZD AED in pediatric rSE. These
      factors identify potential targets for intervention to reduce time to treatment.

PMID- 29643087
TI  - Selection of morphological features of pollen grains for chosen tree taxa.
AB  - The basis of aerobiological studies is to monitor airborne pollen concentrations
      and pollen season timing. This task is performed by appropriately trained staff
      and is difficult and time consuming. The goal of this research is to select
      morphological characteristics of grains that are the most discriminative for
      distinguishing between birch, hazel and alder taxa and are easy to determine
      automatically from microscope images. This selection is based on the split
      attributes of the J4.8 classification trees built for different subsets of
      features. Determining the discriminative features by this method, we provide
      specific rules for distinguishing between individual taxa, at the same time
      obtaining a high percentage of correct classification. The most discriminative
      among the 13 morphological characteristics studied are the following: number of
      pores, maximum axis, minimum axis, axes difference, maximum oncus width, and
      number of lateral pores. The classification result of the tree based on this
      subset is better than the one built on the whole feature set and it is almost
      94%. Therefore, selection of attributes before tree building is recommended. The
      classification results for the features easiest to obtain from the image, i.e.
      maximum axis, minimum axis, axes difference, and number of lateral pores, are
      only 2.09 pp lower than those obtained for the complete set, but 3.23 pp lower
      than the results obtained for the selected most discriminating attributes only.

PMID- 29643090
TI  - A question of 'fairness': Why ethics should factor in the Court of Arbitration
      for Sport's decision on the IAAF Hyperandrogenism Regulations.

PMID- 29643089
TI  - Physicians' political preferences and the delivery of end of life care in the
      United States: retrospective observational study.
AB  - OBJECTIVES: To compare the delivery of end of life care given to US Medicare
      beneficiaries in hospital by internal medicine physicians with Republican versus
      Democrat political affiliations. DESIGN: Retrospective observational study.
      SETTING: US Medicare. PARTICIPANTS: Random sample of Medicare beneficiaries, who
      were admitted to hospital in 2008-12 with a general medical condition, and died
      in hospital or shortly thereafter. MAIN OUTCOME MEASURES: Total inpatient
      spending, intensive care unit use, and intensive end of life treatments (eg,
      mechanical ventilation and gastrostomy tube insertion) among patients dying in
      hospital, and hospice referral among patients discharged but at high predicted
      risk of 30 day mortality after discharge. Physicians were categorized as
      Democrat, Republican, or non-donors, using federal political contribution data.
      RESULTS: Among 1 480 808 patients, 93 976 (6.3%) were treated by 1523 Democratic
      physicians, 58 876 (4.0%) by 768 Republican physicians, and 1 327 956 (89.6%) by
      23 627 non-donor physicians. Patient demographics and clinical characteristics
      were similar between groups. Democrat physicians were younger, more likely to be
      female, and more likely to have graduated from a top 20 US medical school than
      Republican physicians. Mean end of life spending, after adjustment for patient
      covariates and hospital specific fixed effects, was US$17 938 (L12 872; ?14 612)
      among Democrat physicians (95% confidence interval $17 176 to $18 700) and $18
      409 among Republican physicians ($17 362 to $19 456; adjusted Republican v
      Democrat difference, $472 (-$803 to $1747), P=0.47). Intensive end of life
      treatments for patients who died in hospital did not vary by physician political
      affiliation. The proportion of patients discharged from hospital to hospice did
      not vary with physician political affiliation. Among patients in the top 5% of
      predicted risk of death 30 days after hospital discharge, adjusted proportions of
      patients discharged to hospice were 15.8%, 15.0%, and 15.2% among Democrat,
      Republican, and non-donor physicians, respectively (adjusted difference in
      proportion between Republicans v Democrats, -0.8% (-2.7% to 0.9%), P=0.43).
      CONCLUSIONS: This study provided no evidence that physician political affiliation
      is associated with the intensity of end of life care received by patients in
      hospital. Other treatments for politically polarised healthcare issues should be
      investigated.

PMID- 29643091
TI  - Do not throw the baby out with the bathwater; screening can identify meaningful
      risk factors for sports injuries.

PMID- 29643092
TI  - Advertising paid and unpaid job roles in sport: an updated position statement
      from the UK Strength and Conditioning Association.

PMID- 29643094
TI  - Private sector hospitals must improve safety, says CQC.

PMID- 29643097
TI  - Drug misuse at heart of strategy to reduce violent crime.

PMID- 29643096
TI  - The health, poverty, and financial consequences of a cigarette price increase
      among 500 million male smokers in 13 middle income countries: compartmental model
      study.
AB  - OBJECTIVE: To examine the impact of a 50% increase in market prices of cigarettes
      on health, poverty, and financial protection. DESIGN: Compartmental model study.
      SETTING: 13 middle income countries, totalling two billion men. PARTICIPANTS: 500
      million male smokers. MAIN OUTCOME MEASURES: Life years gained, averted treatment
      costs, number of men avoiding catastrophic healthcare expenditures and poverty,
      and additional tax revenue by income group. RESULTS: A 50% increase in cigarette
      prices would lead to about 450 million years of life gained across the 13
      countries from smoking cessation, with half of these in China. Across all
      countries, men in the bottom income group (poorest 20% of the population) would
      gain 6.7 times more life years than men in the top income group (richest 20% of
      the population; 155 v 23 million). The average life years gained from cessation
      for each smoker in the bottom income group was 5.1 times that of the top group
      (1.46 v 0.23 years). Of the $157bn (L113bn; ?127bn) in averted treatment costs,
      the bottom income group would avert 4.6 times more costs than the top income
      group ($46bn v $10bn). About 15.5 million men would avoid catastrophic health
      expenditures in a subset of seven countries without universal health coverage. As
      result, 8.8 million men, half of them in the bottom income group, would avoid
      falling below the World Bank definition of extreme poverty. These 8.8 million men
      constitute 2.4% of people living in extreme poverty in these countries. In
      contrast, the top income group would pay twice as much as the bottom income group
      of the $122bn additional tax collected. Overall, the bottom income group would
      get 31% of the life years saved and 29% each of the averted disease costs and
      averted catastrophic health expenditures, while paying only 10% of the additional
      taxes. CONCLUSIONS: Higher prices of cigarettes provide more health and financial
      gains to the poorest 20% than to the richest 20% of the population. Higher excise
      taxes support the targets of the sustainable development goals on non
      communicable diseases and poverty, and provides financial protection against
      illness.

PMID- 29643098
TI  - Low cigarette consumption and risk of coronary heart disease and stroke: meta
      analysis of 141 cohort studies in 55 study reports.

PMID- 29643099
TI  - Increasing inhaled steroid dose in asthma exacerbations.

PMID- 29643100
TI  - Overdiagnosis and child health.

PMID- 29643101
TI  - Fracture of the clavicle or skeletal disorder?

PMID- 29643103
TI  - Alveolar echinococcosis in the liver of an adolescent boy.

PMID- 29643102
TI  - Research priority setting in childhood chronic disease: a systematic review.
AB  - OBJECTIVE: To evaluate research priority setting approaches in childhood chronic
      diseases and to describe the priorities of stakeholders including patients,
      caregivers/families and health professionals. DESIGN: We conducted a systematic
      review of MEDLINE, Embase, PsycINFO and CINAHL from inception to 16 October 2016.
      Studies that elicited stakeholder priorities for paediatric chronic disease
      research were eligible for inclusion. Data on the prioritisation process were
      extracted using an appraisal checklist. Generated priorities were collated into
      common topic areas. RESULTS: We identified 83 studies (n=15 722). Twenty (24%)
      studies involved parents/caregivers and four (5%) children. The top three health
      areas were cancer (11%), neurology (8%) and endocrine/metabolism (8%). Priority
      topic areas were treatment (78%), disease trajectory (48%), quality of
      life/psychosocial impact (48%), disease onset/prevention (43%), knowledge/self
      management (33%), prevalence (30%), diagnostic methods (28%), access to
      healthcare (25%) and transition to adulthood (12%). The methods included
      workshops, Delphi techniques, surveys and focus groups/interviews. Specific
      methods for collecting and prioritising research topics were described in only
      60% of studies. Most reviewed studies were conducted in high-income nations.
      CONCLUSIONS: Research priority setting activities in paediatric chronic disease
      cover many discipline areas and have elicited a broad range of topics. However,
      child/caregiver involvement is uncommon, and the methods often lack clarity. A
      systematic and explicit process that involves patients and families in
      partnership may help to inform a more patient and family-relevant research agenda
      in paediatric chronic disease.

PMID- 29643104
TI  - Actigraphy assessment of sleep quality among patients with acute myeloid
      leukaemia during induction chemotherapy.
AB  - OBJECTIVES: Patients receiving induction chemotherapy for acute myeloid leukaemia
      (AML) anecdotally describe poor sleep, but sleep disturbances have not been well
      characterised in this population. We aimed to test the feasibility of measuring
      sleep quality in AML inpatients using a wearable actigraphy device. METHODS:
      Using the Actigraph GT3X 'watch', we assessed the total sleep time, sleep onset
      latency, wake after sleep onset, number of awakenings after sleep onset and sleep
      efficiency for inpatients with AML receiving induction chemotherapy. We assessed
      patient self-reported sleep quality using the Pittsburgh Sleep Quality Index
      (PSQI). RESULTS: Of the 12 patients enrolled, 11 completed all actigraphy and
      PSQI assessments, demonstrating feasibility. Patients wore the Actigraph device
      for a mean (SD) of 15.92 (8.3) days, and actigraphy measures suggested poor
      sleep. Patients had a median average awakening length of 6.92 min, a median
      number of awakenings after sleep onset of 4 and a median sleep onset latency of
      10.8 min. Actual median sleep efficiency (0.91) was high, suggesting that
      patients' poor sleep was not due to insomnia but perhaps due to interruptions,
      such as administration of medications, lab draws and vital sign measurements.
      CONCLUSIONS: Collection of sleep quality data among inpatients with AML via a
      wearable actigraphy device is feasible. AML inpatients appear to have poor sleep
      quality and quantity, suggesting that sleep issues represent an area of unmet
      supportive care needs in AML. Further research in this areas is needed to inform
      the development of interventions to improve sleep duration and quality in
      hospitalised patients with AML.

PMID- 29643106
TI  - The benefits of taxing cigarettes in middle income countries.

PMID- 29643105
TI  - A next-generation sequencing-based assay for minimal residual disease assessment
      in AML patients with FLT3-ITD mutations.
AB  - Internal tandem duplications in fms-like tyrosine kinase 3 (FLT3-ITDs) are common
      in acute myeloid leukemia (AML) and confer a poor prognosis. A sensitive and
      specific assay for the detection of minimal residual disease (MRD) in FLT3-ITD
      mutated AML could guide therapy decisions. Existing assays for MRD in FLT3-ITD
      AML have not been particularly useful because of limited sensitivity. We
      developed a sensitive and specific MRD assay for FLT3-ITD mutations using next
      generation sequencing. The initial validation of this assay was performed by
      spiking fixed amounts of mutant DNA into wild-type DNA to establish a sensitivity
      of detection equivalent to >=1 FLT3-ITD-containing cell in 10 000, with a minimum
      input of 100 000 cell equivalents of DNA. We subsequently validated the assay in
      bone marrow samples from patients with FLT3-ITD AML in remission. Finally, we
      analyzed bone marrow samples from 80 patients with FLT3-ITD relapsed/refractory
      AML participating in a trial of a novel FLT3 inhibitor, gilteritinib, and
      demonstrated a relationship between the mutation burden, as detected by the
      assay, and overall survival. This novel MRD assay is specific and 2 orders of
      magnitude more sensitive than currently available polymerase chain reaction- or
      next-generation sequencing-based FLT3-ITD assays. The assay is being
      prospectively validated in ongoing randomized clinical trials.

PMID- 29643107
TI  - Time to personalize the treatment of anti-MDA-5 associated lung disease.

PMID- 29643109
TI  - Response to: 'Postpartum breastfeeding status' by Betzold.

PMID- 29643108
TI  - Treating juvenile idiopathic arthritis to target: recommendations of an
      international task force.
AB  - Recent therapeutic advances in juvenile idiopathic arthritis (JIA) have made
      remission an achievable goal for most patients. Reaching this target leads to
      improved outcomes. The objective was to develop recommendations for treating JIA
      to target. A Steering Committee formulated a set of recommendations based on
      evidence derived from a systematic literature review. These were subsequently
      discussed, amended and voted on by an international Task Force of 30 paediatric
      rheumatologists in a consensus-based, Delphi-like procedure. Although the
      literature review did not reveal trials that compared a treat-to-target approach
      with another or no strategy, it provided indirect evidence regarding an optimised
      approach to therapy that facilitated development of recommendations. The group
      agreed on six overarching principles and eight recommendations. The main
      treatment target, which should be based on a shared decision with
      parents/patients, was defined as remission, with the alternative target of low
      disease activity. The frequency and timeline of follow-up evaluations to ensure
      achievement and maintenance of the target depend on JIA category and level of
      disease activity. Additional recommendations emphasise the importance of ensuring
      adequate growth and development and avoiding long-term systemic glucocorticoid
      administration to maintain the target. All items were agreed on by more than 80%
      of the members of the Task Force. A research agenda was formulated. The Task
      Force developed recommendations for treating JIA to target, being aware that the
      evidence is not strong and needs to be expanded by future research. These
      recommendations can inform various stakeholders about strategies to reach optimal
      outcomes for JIA.

PMID- 29643110
TI  - Postpartum breastfeeding status.

PMID- 29643112
TI  - What they say and what they do: comparing physical activity across the USA,
      England and the Netherlands.
AB  - BACKGROUND: Physical activity (PA) is important for maintaining health, but there
      are fundamental unanswered questions on how best it should be measured. METHODS:
      We measured PA in the Netherlands (n=748), the USA (n=540) and England (n=254),
      both by a 7 day wrist-worn accelerometer and by self-reports. The self-reports
      included a global self-report on PA and a report on the frequency of vigorous,
      moderate and mild activity. RESULTS: The self-reported data showed only minor
      differences across countries and across groups within countries (such as
      different age groups or working vs non-working respondents). The accelerometer
      data, however, showed large differences; the Dutch and English appeared to be
      much more physically active than Americans h (For instance, among respondents
      aged 50 years or older 38% of Americans are in the lowest activity quintile of
      the Dutch distribution). In addition, accelerometer data showed a sharp decline
      of PA with age, while no such pattern was observed in self-reports. The
      differences between objective measures and self-reports occurred for both types
      of self-reports. CONCLUSION: It is clear that self-reports and objective measures
      tell vastly different stories, suggesting that across countries people use
      different response scales when answering questions about how physically active
      they are.

PMID- 29643111
TI  - Cardiovascular and Cerebrovascular Emergency Department Visits Associated With
      Wildfire Smoke Exposure in California in 2015.
AB  - BACKGROUND: Wildfire smoke is known to exacerbate respiratory conditions;
      however, evidence for cardiovascular and cerebrovascular events has been
      inconsistent, despite biological plausibility. METHODS AND RESULTS: A population
      based epidemiologic analysis was conducted for daily cardiovascular and
      cerebrovascular emergency department (ED) visits and wildfire smoke exposure in
      2015 among adults in 8 California air basins. A quasi-Poisson regression model
      was used for zip code-level counts of ED visits, adjusting for heat index, day of
      week, seasonality, and population. Satellite-imaged smoke plumes were classified
      as light, medium, or dense based on model-estimated concentrations of fine
      particulate matter. Relative risk was determined for smoky days for lag days 0 to
      4. Rates of ED visits by age- and sex-stratified groups were also examined. Rates
      of all-cause cardiovascular ED visits were elevated across all lags, with the
      greatest increase on dense smoke days and among those aged >=65 years at lag 0
      (relative risk 1.15, 95% confidence interval [1.09, 1.22]). All-cause
      cerebrovascular visits were associated with smoke, especially among those 65
      years and older, (1.22 [1.00, 1.49], dense smoke, lag 1). Respiratory conditions
      were also increased, as anticipated (1.18 [1.08, 1.28], adults >65 years, dense
      smoke, lag 1). No association was found for the control condition, acute
      appendicitis. Elevated risks for individual diagnoses included myocardial
      infarction, ischemic heart disease, heart failure, dysrhythmia, pulmonary
      embolism, ischemic stroke, and transient ischemic attack. CONCLUSIONS: Analysis
      of an extensive wildfire season found smoke exposure to be associated with
      cardiovascular and cerebrovascular ED visits for all adults, particularly for
      those over aged 65 years.

PMID- 29643113
TI  - Pasireotide in the treatment of neuroendocrine tumors: a review of the
      literature.
AB  - Somatostatin analogs have an important role in the medical therapy of
      neuroendocrine tumors (NETs). Octreotide and lanreotide, both somatostatin
      analogs binding with high affinity for the somatostatin receptor (SSTR)2, can
      control symptoms in functional NETs. In addition, these compounds, because of
      their antiproliferative effects, can stabilize growth of well-differentiated
      NETs. Pasireotide is a novel multireceptor-targeted somatostatin analog with high
      affinity for SSTR1, 2, 3, and 5. This review provides an overview of the state of
      the art of pasireotide in the treatment of NETs, with the aim of addressing
      clinical relevance and future perspectives for this molecule in the management of
      NETs.

PMID- 29643114
TI  - Using Large Datasets to Understand CKD.

PMID- 29643116
TI  - Dynamic visits of cortical structures probe for cell size.
AB  - All cells show size homeostasis owing to coordination of division with growth. In
      this issue, Allard et al. (2018. J. Cell Biol.
      https://doi.org/10.1083/jcb.201709171) establish that transient inhibitory visits
      of a negative regulator of Cdk1 to cortical oligomeric platforms increase in
      number and duration with cell growth, suggesting how Cdk1 activation is coupled
      to cell size.

PMID- 29643115
TI  - Chronic AT1 blockade improves glucose homeostasis in obese OLETF rats.
AB  - Obesity is associated with the inappropriate activation of the renin-angiotensin
      system (RAS), which increases arterial pressure, impairs insulin secretion and
      decreases peripheral tissue insulin sensitivity. RAS blockade reverses these
      detriments; however, it is not clear whether the disease state of the organism
      and treatment duration determine the beneficial effects of RAS inhibition on
      insulin secretion and insulin sensitivity. Therefore, the objective of this study
      was to compare the benefits of acute vs chronic angiotensin receptor type 1 (AT1)
      blockade started after the onset of obesity, hyperglycemia and hypertension on
      pancreatic function and peripheral insulin resistance. We assessed adipocyte
      morphology, glucose intolerance, pancreatic redox balance and insulin secretion
      after 2 and 11 weeks of AT1 blockade in the following groups of rats: (1)
      untreated Long-Evans Tokushima Otsuka (lean control; n = 10), (2) untreated
      Otsuka Long-Evans Tokushima Fatty (OLETF; n = 12) and (3) OLETF + ARB (ARB; 10 mg
      olmesartan/kg/day by oral gavage; n = 12). Regardless of treatment duration, AT1
      blockade decreased systolic blood pressure and fasting plasma triglycerides,
      whereas chronic AT1 blockade decreased fasting plasma glucose, glucose
      intolerance and the relative abundance of large adipocytes by 22, 36 and 70%,
      respectively. AT1 blockade, however, did not improve pancreatic oxidative stress
      or reverse impaired insulin secretion. Collectively, these data show that AT1
      blockade after the onset of obesity, hyperglycemia and hypertension improves
      peripheral tissue insulin sensitivity, but cannot completely reverse the
      metabolic derangement characterized by impaired insulin secretion once it has
      been compromised.

PMID- 29643117
TI  - SFT-4/Surf4 control ER export of soluble cargo proteins and participate in ER
      exit site organization.
AB  - Lipoproteins regulate the overall lipid homeostasis in animals. However, the
      molecular mechanisms underlying lipoprotein trafficking remain poorly understood.
      Here, we show that SFT-4, a Caenorhabditis elegans homologue of the yeast Erv29p,
      is essential for the endoplasmic reticulum (ER) export of the yolk protein VIT-2,
      which is synthesized as a lipoprotein complex. SFT-4 loss strongly inhibits the
      ER exit of yolk proteins and certain soluble cargo proteins in intestinal cells.
      SFT-4 predominantly localizes at ER exit sites (ERES) and physically interacts
      with VIT-2 in vivo, which suggests that SFT-4 promotes the ER export of soluble
      proteins as a cargo receptor. Notably, Surf4, a mammalian SFT-4 homologue,
      physically interacts with apolipoprotein B, a very-low-density lipoprotein core
      protein, and its loss causes ER accumulation of apolipoprotein B in human hepatic
      HepG2 cells. Interestingly, loss of SFT-4 and Surf4 reduced the number of COPII
      positive ERES. Thus, SFT-4 and Surf4 regulate the export of soluble proteins,
      including lipoproteins, from the ER and participate in ERES organization in
      animals.

PMID- 29643118
TI  - TFIIH localization is highly dynamic during zygotic genome activation in
      Drosophila, and its depletion causes catastrophic mitosis.
AB  - In Drosophila, zygotic genome activation occurs in pre-blastoderm embryos during
      rapid mitotic divisions. How the transcription machinery is coordinated to
      achieve this goal in a very brief time span is still poorly understood.
      Transcription factor II H (TFIIH) is fundamental for transcription initiation by
      RNA polymerase II (RNAPII). Herein, we show the in vivo dynamics of TFIIH at the
      onset of transcription in Drosophila embryos. TFIIH shows an oscillatory
      behaviour between the nucleus and cytoplasm. TFIIH foci are observed from
      interphase to metaphase, and colocalize with those for RNAPII phosphorylated at
      serine 5 (RNAPIIS5P) at prophase, suggesting that transcription occurs during the
      first mitotic phases. Furthermore, embryos with defects in subunits of either the
      CAK or the core subcomplexes of TFIIH show catastrophic mitosis. Although,
      transcriptome analyses show altered expression of several maternal genes that
      participate in mitosis, the global level of RNAPIIS5P in TFIIH mutant embryos is
      similar to that in the wild type, therefore, a direct role for TFIIH in mitosis
      cannot be ruled out. These results provide important insights regarding the role
      of a basal transcription machinery component when the zygotic genome is
      activated.

PMID- 29643119
TI  - Regulator of calcineurin-2 is a centriolar protein with a role in cilia length
      control.
AB  - Almost every cell in the human body extends a primary cilium. Defective cilia
      function leads to a set of disorders known as ciliopathies, which are
      characterised by debilitating developmental defects that affect many tissues.
      Here, we report a new role for regulator of calcineurin 2 (RCAN2) in primary
      cilia function. It localises to centrioles and the basal body and is required to
      maintain normal cilia length. RCAN2 was identified as the most strongly
      upregulated gene from a comparative RNAseq analysis of cells in which expression
      of the Golgi matrix protein giantin had been abolished by gene editing. In
      contrast to previous work where we showed that depletion of giantin by RNAi
      results in defects in ciliogenesis and in cilia length control, giantin knockout
      cells generate normal cilia after serum withdrawal. Furthermore, giantin knockout
      zebrafish show increased expression of RCAN2. Importantly, suppression of RCAN2
      expression in giantin knockout cells results in the same defects in the control
      of cilia length that are seen upon RNAi of giantin itself. Together, these data
      define RCAN2 as a regulator of cilia function that can compensate for the loss of
      giantin function.

PMID- 29643121
TI  - FAST in the deployed military setting.
AB  - INTRODUCTION: Focused assessment with sonography in trauma (FAST) is historically
      an effective method of assessing the patient in the trauma bay in order to aid
      decision-making and optimise patient outcomes. However, in the UK civilian
      practice, the use of FAST may decline given a recent change in National Institute
      for Health and Care Excellence guidance as a result of improvement in CT
      availability and resuscitation techniques. METHOD: In the Role 3 Medical
      Treatment Facility, Camp Bastion, 187 patients with trauma who received FAST in
      the trauma bay in 2014 were reviewed to determine the accuracy of FAST in the
      deployed environment. RESULTS: The data demonstrates the sensitivity and
      specificity of FAST to be 75% and 99.3%, respectively. CONCLUSIONS: This study
      demonstrates that FAST is accurate on operations. FAST is provided by the
      integrated radiologist as part of damage control radiology, which gives the team
      leader rapid diagnostic information to improve decision-making and ultimately
      patient outcomes. CT is heavily utilised in civilian practice; however, the
      military operates in a different environment often with multiple casualties and
      limited access to CT, as a result, portable ultrasound will continue to be a
      valuable tool on operations if used properly. The next challenge is to develop
      and maintain this high diagnostic accuracy in future deployments where the
      memories of our prior success may fade.

PMID- 29643120
TI  - EphrinB2/EphB4 signaling regulates non-sprouting angiogenesis by VEGF.
AB  - Vascular endothelial growth factor (VEGF) is the master regulator of
      angiogenesis, whose best-understood mechanism is sprouting. However, therapeutic
      VEGF delivery to ischemic muscle induces angiogenesis by the alternative process
      of intussusception, or vascular splitting, whose molecular regulation is
      essentially unknown. Here, we identify ephrinB2/EphB4 signaling as a key
      regulator of intussusceptive angiogenesis and its outcome under therapeutically
      relevant conditions. EphB4 signaling fine-tunes the degree of endothelial
      proliferation induced by specific VEGF doses during the initial stage of
      circumferential enlargement of vessels, thereby limiting their size and
      subsequently enabling successful splitting into normal capillary networks.
      Mechanistically, EphB4 neither inhibits VEGF-R2 activation by VEGF nor its
      internalization, but it modulates VEGF-R2 downstream signaling through phospho
      ERK1/2. In vivo inhibitor experiments show that ERK1/2 activity is required for
      EphB4 regulation of VEGF-induced intussusceptive angiogenesis. Lastly, after
      clinically relevant VEGF gene delivery with adenoviral vectors, pharmacological
      stimulation of EphB4 normalizes dysfunctional vascular growth in both normoxic
      and ischemic muscle. These results identify EphB4 as a druggable target to
      modulate the outcome of VEGF gene delivery and support further investigation of
      its therapeutic potential.

PMID- 29643122
TI  - Guidelines for using animal models in blast injury research.
AB  - Blast injury is a very complex phenomenon and frequently results in multiple
      injuries. One method to investigate the consequences of blast injuries is with
      the use of living systems (animal models). The use of animals allows the
      examination and evaluation of injury mechanisms in a more controlled manner,
      allowing variables such as primary or secondary blast injury for example, to be
      isolated and manipulated as required. To ensure a degree of standardisation
      across the blast research community a set of guidelines which helps researchers
      navigate challenges of modelling blast injuries in animals is required. This
      paper describes the guidelines for Using Animal Models in Blast Injury Research
      developed by the NATO Health Factors and Medicine (HFM) Research Task Group 234.

PMID- 29643123
TI  - Intragenic transcriptional interference regulates the human immune ligand MICA.
AB  - Many human genes have tandem promoters driving overlapping transcription, but the
      value of this distributed promoter configuration is generally unclear. Here we
      show that MICA, a gene encoding a ligand for the activating immune receptor
      NKG2D, contains a conserved upstream promoter that expresses a noncoding
      transcript. Transcription from the upstream promoter represses the downstream
      standard promoter activity in cis through transcriptional interference. The
      effect of transcriptional interference depends on the strength of transcription
      from the upstream promoter and can be described quantitatively by a simple
      reciprocal repressor function. Transcriptional interference coincides with
      recruitment at the standard downstream promoter of the FACT histone chaperone
      complex, which is involved in nucleosomal remodelling during transcription. The
      mechanism is invoked in the regulation of MICA expression by the physiological
      inputs interferon-gamma and interleukin-4 that act on the upstream promoter.
      Genome-wide analysis indicates that transcriptional interference between tandem
      intragenic promoters may constitute a general mechanism with widespread
      importance in human transcriptional regulation.

PMID- 29643124
TI  - Myocardial ischaemia as a result of external coronary compression from infective
      aortic root aneurysm: atypical presentation of prosthetic valve endocarditis.
AB  - : SummaryThis case describes an unusual presentation of prosthetic valve
      endocarditis (PVE): an acute coronary syndrome. A 67-year-old male presented with
      cardiac sounding chest pain on a background of a short history of night sweats,
      weight loss and general malaise. Four months previously, he had undergone bio
      prosthetic aortic valve replacement for severe aortic stenosis and single vessel
      bypass grafting of the obtuse marginal. Whilst having chest pain, his ECG showed
      infero-lateral ST depression. Early coronary angiography revealed a new right
      coronary artery (RCA) lesion that was not present prior to his cardiac surgery.
      Using multi-modality cardiac imaging, the diagnosis of PVE was made. An aortic
      root abscess was demonstrated that was causing external compression of the RCA.
      LEARNING POINTS: PVE accounts for up to 20% of all cases of infective
      endocarditis.High clinical suspicion and early blood cultures before empirical
      antibiotics are key as the presentation of PVE can often be atypical.PVE rarely
      presents as an acute coronary syndrome. Potential mechanisms by which PVE may
      result in an ACS include coronary embolization, obstruction of coronary ostia by
      a large mobile vegetation and external coronary artery compression from an
      infective aneurysms/abscess.Repeat cardiac surgery is often required for high
      risk PVE such as those caused by staphylococcal infection or severe prosthetic
      dysfunction.

PMID- 29643125
TI  - What is the minimum change in left ventricular ejection fraction, which can be
      measured with contrast echocardiography?
AB  - BACKGROUND: There are limited data on what is the minimum change that can be
      detected in cancer patients undergoing treatment with cardiotoxic drugs and are
      referred for monitoring left ventricular (LV) function. OBJECTIVE: To assess the
      variability in the measurement of LV volumes and ejection fraction (EF) in
      contrast echocardiography and to determine the minimum detectable difference
      (MDD) between two EF measurements that can be deemed significant. METHODS: A
      total of 150 patients were divided into three groups according to EF (EF <53, 53
      60, and >60%). Each group consisted of 50 randomly selected cancer patients who
      underwent contrast echocardiography between July 2010 and May 2014. Repeated
      measurements of LV volumes and EF were performed offline by a sonographer and a
      cardiologist. Inter-observer variability was assessed by analysis of variance.
      Measurement error was estimated by standard error of measurement and MDD.
      RESULTS: The 95% confidence interval with a single measurement of EF was 2
      percentage points in the groups of patients with EF <53% and EF >60%, and 2.5
      percentage points for patients with EF 53-60%. The MDD for EF, end-diastolic
      volume and end-systolic volume that could be recognized with 95% confidence
      interval were 4 percentage points, 7 mL and 4 mL, respectively. CONCLUSION:
      Contrast echocardiography is a reliable tool for serial measurements of EF to
      monitor cardiotoxicity due to chemotherapy. In a high-volume echocardiography
      laboratory with experienced staff, the MDD for EF of 4 percentage points on a
      good-quality recording demonstrates the high reproducibility of the Simpson's
      method using contrast echocardiography.

PMID- 29643126
TI  - Case of membranous oesophageal atresia.

PMID- 29643127
TI  - Breastfeeding rates at discharge: don't blame the fortifier! A national survey of
      practice and comparison with NNAP data.

PMID- 29643128
TI  - Effects of Impella on Coronary Perfusion in Patients With Critical Coronary
      Artery Stenosis.
AB  - BACKGROUND: Mechanical circulatory support devices are used to maintain
      hemodynamic stability during high-risk percutaneous coronary interventions.
      Little is known on the effects of such devices on coronary hemodynamics in
      patients with significant coronary stenosis. We sought to investigate whether
      mechanical circulatory support in the form of Impella (Abiomed Inc, Danvers, MA)
      can improve coronary hemodynamics in the presence of a critical coronary
      stenosis. METHODS AND RESULTS: We examined coronary perfusion pressures and
      coronary pressure distal to a critical stenosis using a coronary pressure wire in
      11 patients (12 coronary lesions) undergoing high-risk percutaneous coronary
      interventions with the use of mechanical circulatory support. Systemic,
      ventricular, and coronary hemodynamics were obtained at both minimum and maximum
      support levels before high-risk percutaneous coronary interventions. All patients
      had obstructive lesions with angiographically estimated diameter stenosis between
      70% and 99% and distal coronary artery pressure to aortic pressure ratios between
      0.44 and 0.88. When compared with minimum support, maximum support resulted in a
      decrease in the left ventricular end-diastolic pressure (27.3+/-8.6 versus 21.5+/
      5.2 mm Hg; P=0.002) and increases in the mean systemic blood pressure (77.6+/
      13.5 versus 88.2+/-12.2 mm Hg; P<0.001) and mean distal coronary pressure (51.8+/
      20.2 versus 60.8+/-18.1 mm Hg; P<0.001). Effective coronary perfusion pressure
      (mean aortic pressure-left ventricular end-diastolic pressure) significantly
      increased with maximum support (49.8+/-15.7 versus 67.2+/-13.6 mm Hg; P<0.001).
      Diastolic perfusion pressure (diastolic blood pressure-left ventricular end
      diastolic pressure) also significantly increased with maximum support (32.9+/
      13.4 versus 52.0+/-11.6 mm Hg; P<0.001). CONCLUSIONS: Mechanical circulatory
      support with Impella can improve distal coronary pressure and coronary perfusion
      pressures in the presence of critical coronary stenosis.

PMID- 29643129
TI  - Vessel Stretching Is a Cause of Lumen Enlargement Immediately After Balloon
      Pulmonary Angioplasty: Intravascular Ultrasound Analysis in Patients With Chronic
      Thromboembolic Pulmonary Hypertension.
AB  - BACKGROUND: Balloon pulmonary angioplasty (BPA) has become an alternative therapy
      for patients with chronic thromboembolic pulmonary hypertension who are
      ineligible for pulmonary endarterectomy. We retrospectively investigated
      intravascular ultrasound measurements to elucidate how the lumen enlarges
      immediately after BPA. METHODS AND RESULTS: A total of 326 lesions in 71 patients
      with chronic thromboembolic pulmonary hypertension were analyzed. The cross
      sectional areas (CSAs) of the external elastic membrane and lumen measured by
      intravascular ultrasound before and after BPA were assessed for each lesion type
      (type A, ring-like stenosis lesions; type B, web lesions; type C, subtotal
      occlusion lesions). Comparing the lesion types, the proportion of the area
      occupied by fibrous tissue was smallest in the type A lesions and largest in the
      type C lesions. The mean lesion lumen CSA was increased after BPA because of an
      increase in external elastic membrane CSA (from 23.2+/-12.9 to 27.2+/-14.3 mm2;
      P<0.001) with a slight decrease in fibrous tissue plus media CSA (from 17.7+/
      11.7 to 17.3+/-11.1 mm2; P<0.001). The change in lumen CSA correlated strongly
      with the change in external elastic membrane CSA (r2=0.762; P<0.001).
      CONCLUSIONS: Lumen enlargement immediately after BPA was obtained by the overall
      vessel expansion induced by a stretch of the arterial wall. In addition, the
      amount of fibrous tissue depended on each lesion type. Thus, it might be
      beneficial to change the balloon size to correspond with the lesion type.

PMID- 29643131
TI  - Rumpel-Leede Phenomenon After Radial Artery Catheterization.

PMID- 29643130
TI  - Transcatheter Versus Surgical Aortic Valve Replacement in Patients With Prior
      Coronary Artery Bypass Grafting: Trends in Utilization and Propensity-Matched
      Analysis of In-Hospital Outcomes.
AB  - BACKGROUND: A significant proportion of patients requiring aortic valve
      replacement (AVR) have undergone prior coronary artery bypass grafting (CABG).
      Reoperative heart surgery is associated with increased risk. Data on relative
      utilization and comparative outcomes of transcatheter (TAVR) versus surgical AVR
      (SAVR) in patients with prior CABG are limited. METHODS AND RESULTS: We queried
      the 2012 to 2014 National Inpatient Sample databases to identify isolated AVR
      hospitalizations in adults with prior CABG. In-hospital outcomes of TAVR versus
      SAVR were compared using propensity-matched analysis. Of 147 395 AVRs, 15 055
      (10.2%) were in patients with prior CABG. The number of TAVRs in patients with
      prior CABG increased from 1615 in 2012 to 4400 in 2014, whereas the number of
      SAVRs decreased from 2285 to 1895 (Ptrend<0.001). There were 3880 records in each
      group in the matched cohort. Compared with SAVR, TAVR was associated with similar
      in-hospital mortality (2.3% versus 2.4%; P=0.71) but lower incidence of
      myocardial infarction (1.5% versus 3.4%; P<0.001), stroke (1.4% versus 2.7%;
      P<0.001), bleeding complications (10.6% versus 24.6%; P<0.001), and acute kidney
      injury (16.2% versus 19.3%; P<0.001). Requirement for prior permanent pacemaker
      was higher in the TAVR cohort, whereas the incidence of vascular complications
      and acute kidney injury requiring dialysis was similar in the 2 groups. Average
      length of stay was shorter in patients undergoing TAVR. CONCLUSIONS: TAVR is
      being increasingly used as the preferred modality of AVR in patients with prior
      CABG. Compared with SAVR, TAVR is associated with similar in-hospital mortality
      but lower rates of in-hospital complications in this important subset of
      patients.

PMID- 29643132
TI  - Surgical Versus Transcatheter Aortic Valve Replacement in Patients With Prior
      Coronary Bypass Surgery: Tie Goes to the Runner.

PMID- 29643133
TI  - Treatment-refractory ALK-positive inflammatory myofibroblastic tumour of the oral
      cavity.
AB  - We present a challenging case of a previously healthy 23-year-old man who
      developed an inflammatory myofibroblastic tumour of the hard palate, harbouring a
      rearrangement of the anaplastic lymphoma kinase (ALK) locus. Despite surgical
      intervention, radiotherapy and ALK-inhibition therapy, the tumour recurred
      locally and metastasised to regional lymph nodes, and the patient passed away
      roughly 9 months after diagnosis from local progression. The rapid progression of
      this patient's disease and its resistance to treatment demonstrate the
      potentially aggressive clinical course of inflammatory myofibroblastic tumours.
      ALK-inhibition therapy was unsuccessful in this ALK-positive tumour, highlighting
      the need for further investigation of markers predictive of disease progression
      and treatment response.

PMID- 29643134
TI  - Food-dependent exercise-induced anaphylaxis.
AB  - Food-dependent exercise-induced anaphylaxis (FDEIAn), first reported in 1979, is
      a condition defined by the consumption of a trigger food with temporally related
      exercise that results in an immediate hypersensitivity (type 1) reaction in the
      setting of the trigger food being tolerated independent of exercise and exercise
      being tolerated in the absence of trigger food consumption. The most common
      trigger food in the west is wheat and shellfish in Asia. The exact mechanism of
      FDEIAn is unknown, though several hypotheses exist. Cofactors such as non
      steroidal anti-inflammatory drug use, alcohol consumption and others have been
      associated with reported cases.

PMID- 29643135
TI  - Arthroscopic reduction and fixation of a lateral inverted osteochondral fracture
      of the talus ('LIFT').
AB  - Some ankle sprains hide important lesions beyond the classic lateral ligament
      complex injuries. The lateral inverted osteochondral fracture of the talus (LIFT)
      represents a rare osteochondral lesion, whose diagnosis relies on a high clinical
      suspicion followed by correct image study interpretation. We present a successful
      arthroscopic fixation of a LIFT lesion in a 45-year-old active man. At 8 months
      follow-up, the patient was pain free and able to return to his daily activities
      without limitation. The imagiological study showed osteochondral fragment
      consolidation with no signs of hardware failure. This midterm results reassemble
      the need for early diagnosis and correct treatment to achieve a good outcome in
      these complex and rare osteochondral lesions.

PMID- 29643136
TI  - Orbital metastasis from an occult breast carcinoma (T0, N1, M1).
AB  - The authors report a case of an orbital metastasis from an occult breast
      carcinoma. A 66-year-old woman presented with a growing left orbital tumour.
      Orbital CT scan was consistent with lymphoma. However, ocular pathology revealed
      small neoplastic cells showing an 'indian file pattern' suggestive of metastatic
      carcinoma and immunohistochemistry was positive for CK7, CK CAM5.2 and oestrogen
      receptor. A systemic evaluation was then performed with mammogram, breast
      ultrasound and MRI considered normal. An exhaustive systemic evaluation revealed
      multiple bone lesions, a right axillary lymph node lesion, which presented the
      same pattern on pathology and immunohistochemistry, with no evidence of a primary
      tumour. A diagnosis of a metastatic lobular carcinoma of the breast (T0, N1, M1)
      was made and the patient was started on chemotherapy and adjuvant hormonal
      therapy.

PMID- 29643137
TI  - Sphingomonas paucimobilis empyema caused by remote foreign body aspiration.
AB  - Empyema secondary to foreign body aspiration is rare in adults. We present a case
      of empyema in a 77-year-old male patient related to a remote aspiration event
      during a dental procedure. A CT of the chest and bronchoscopy confirmed that a
      metallic foreign body was located within the right lower lobe bronchus. His
      pleural fluid culture revealed Sphingomonas paucimobilis which is a low-virulent
      opportunistic gram-negative bacilli and rarely causes infection. The patient
      received meropenem followed by levofloxacin and recovered uneventfully. The
      attempt of foreign body removal was failed due to chronic inflammation, and the
      patient refused further surgical management.

PMID- 29643138
TI  - Improvement of thoracic myelopathy following bariatric surgery in an obese
      patient.
AB  - Revision spine surgery is extremely challenging in super-super obese patients
      (body mass index (BMI) >=60 kg/m2). This is the first report describing how
      bariatric surgery was useful for a super-super obese patient with progressing
      myelopathy. A 44-year-old man with a BMI of 62.9 kg/m2 presented with an
      ambulatory disorder caused by thoracic ossification of the posterior longitudinal
      ligament (T7-8). Before this paraparesis, he had undergone four spinal
      operations, and was not considered a good candidate for a fifth spine surgery. At
      the time of the fourth operation, he had reached a maximum weight of 205 kg (BMI
      69.3 kg/m2). Instead, he underwent a laparoscopic sleeve gastrectomy. Sixteen
      months later, his body weight had decreased to BMI 35.2 kg/m2, and he could walk
      without a walker. In addition to reducing our patient's load, a 'non-operative'
      form of dekyphosis due to altered thoracic spinal alignment secondary to weight
      loss may explain the improvement in his myelopathy.

PMID- 29643139
TI  - Pseudoaneurysm of the gastroduodenal artery: an unusual cause for
      hyperamylasaemia.
AB  - A 79-year-old man was admitted electively for investigation of weight loss. While
      he was an inpatient, he developed severe epigastric pain and an initial blood
      test revealed an acutely raised amylase (>2000) and deranged liver function
      tests. A contrast CT angiography showed a large haematoma adjacent to the
      duodenum, spreading in the retroperitoneal space, arising from a 2 cm bleeding
      pseudoaneurysm in the region of the gastroduodenal artery. Due to his underlying
      comorbidities, he was deemed unfit for surgical repair and he had coil
      embolisation with successful haemostasis. The gastroduodenal artery aneurysms are
      rare and constitute 1.5% of all visceral artery aneurysms. They can be an
      incidental finding or they can present with haemorrhagic shock, abdominal pain
      and rarely with obstructive jaundice or hyperamylasaemia. The diagnosis is
      usually made with an angiography. Variable treatment options are available
      depending on the patient's fitness and haemodynamic stability.

PMID- 29643140
TI  - Odynophagia and neck pain after exercise.

PMID- 29643141
TI  - Peripherally inserted central catheter (PICC) placement: beware of the bends.

PMID- 29643142
TI  - Rare and unexpected complication after a malpositioned nasogastric tube in a
      neonate.

PMID- 29643143
TI  - Spontaneous rectus sheath haematoma due to cough on apixaban.

PMID- 29643144
TI  - Inadvertent inflation of Foley catheter balloon with contrast: an error that
      caused unnecessary apprehensions.

PMID- 29643146
TI  - FDA Expands Indication for Nilotinib.
AB  - The FDA expanded the indication for nilotinib for the treatment of children with
      newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in the
      chronic phase who are at least a year old, as well as those who are resistant to
      or cannot tolerate imatinib. The drug is the third tyrosine kinase inhibitor
      approved for children with this rare cancer.

PMID- 29643145
TI  - Single coronary artery with bicuspid aortic valve.

PMID- 29643147
TI  - Ex vivo gut culture for studying differentiation and migration of small
      intestinal epithelial cells.
AB  - Epithelial cultures are commonly used for studying gut health. However, due to
      the absence of mesenchymal cells and gut structure, epithelial culture systems
      including recently developed three-dimensional organoid culture cannot accurately
      represent in vivo gut development, which requires intense cross-regulation of the
      epithelial layer with the underlying mesenchymal tissue. In addition, organoid
      culture is costly. To overcome this, a new culture system was developed using
      mouse embryonic small intestine. Cultured intestine showed spontaneous
      peristalsis, indicating the maintenance of the normal gut physiological
      structure. During 10 days of ex vivo culture, epithelial cells moved along the
      gut surface and differentiated into different epithelial cell types, including
      enterocytes, Paneth cells, goblet cells and enteroendocrine cells. We further
      used the established ex vivo system to examine the role of AMP-activated protein
      kinase (AMPK) on gut epithelial health. Tamoxifen-induced AMPKalpha1 knockout
      vastly impaired epithelial migration and differentiation of the developing ex
      vivo gut, showing the crucial regulatory function of AMPK alpha1 in intestinal
      health.

PMID- 29643149
TI  - Involvement of Prokineticin 2-expressing Neutrophil Infiltration in 5
      Fluorouracil-induced Aggravation of Breast Cancer Metastasis to Lung.
AB  - Adjuvant chemotherapy is used for human breast cancer patients, even after
      curative surgery of primary tumor, to prevent tumor recurrence primarily as a
      form of metastasis. However, anticancer drugs can accelerate metastasis in
      several mouse metastasis models. Hence, we examined the effects of postsurgical
      administration with 5-fluorouracil (5-FU), doxorubicin, and cyclophosphamide, on
      lung metastasis process, which developed after the resection of the primary tumor
      arising from the orthotopic injection of a mouse triple-negative breast cancer
      cell line, 4T1. Only 5-FU markedly increased the numbers and sizes of lung
      metastasis foci, with enhanced tumor cell proliferation and angiogenesis as
      evidenced by increases in Ki67-positive cell numbers and CD31-positive areas,
      respectively. 5-FU-mediated augmented lung metastasis was associated with
      increases in intrapulmonary neutrophil numbers and expression of neutrophilic
      chemokines, Cxcl1 and Cxcl2 in tumor cells, with few effects on intrapulmonary T
      cell or macrophage numbers. 5-FU enhanced Cxcl1 and Cxcl2 expression in 4T1 cells
      in a NFkappaB-dependent manner. Moreover, the administration of a neutrophil
      depleting antibody or a Cxcr2 antagonist, SB225002, significantly attenuated 5-FU
      mediated enhanced lung metastasis with depressed neutrophil infiltration.
      Furthermore, infiltrating neutrophils and 4T1 cells abundantly expressed
      prokineticin-2 (Prok2) and its receptor, Prokr1, respectively. Finally, the
      administration of 5-FU after the resection of the primary tumor failed to augment
      lung metastasis in the mice receiving Prokr1-deleted 4T1 cells. Collectively, 5
      FU can enhance lung metastasis by inducing tumor cells to produce Cxcl1 and
      Cxcl2, which induced the migration of neutrophils expressing Prok2 with a
      capacity to enhance 4T1 cell proliferation. Mol Cancer Ther; 17(7); 1515-25.
      (c)2018 AACR.

PMID- 29643148
TI  - Lysosome-dependent cell death and deregulated autophagy induced by amine-modified
      polystyrene nanoparticles.
AB  - Nanoparticles (NPs) typically accumulate in lysosomes. However, their impact on
      lysosomal function, as well as autophagy, a lysosomal degradative pathway, is
      still not well known. We have previously reported in the 1321N1 cell line that
      amine-modified polystyrene (NH2-PS) NPs induce apoptosis through damage initiated
      in the lysosomes leading ultimately to release of lysosomal content in the
      cytosol, followed by apoptosis. Here, by using a combination of biochemical and
      cell biological approaches, we have characterized in a mouse embryonic fibroblast
      cell line that the lysosomal alterations induced by NH2-PS NPs is progressive,
      initiating from mild lysosomal membrane permeabilization (LMP), to expansion of
      lysosomal volume and intensive LMP before the summit of cell death. Though the
      cells initially seem to induce autophagy as a surviving mechanism, the damage of
      NH2-PS NPs to lysosomes probably results in lysosomal dysfunctions, leading to
      blockage of autophagic flux at the level of lysosomes and the eventual cell
      death.

PMID- 29643150
TI  - Rate of adherence to urate-lowering therapy among patients with gout: a
      systematic review and meta-analysis.
AB  - INTRODUCTION: Reported adherence to urate-lowering therapy (ULT) in gout varies
      widely (17%-83.5%). Variability may partly be due to different adherence
      measurement methods. This review aimed to quantify ULT adherence in adult
      patients with gout. METHODS: This analysis examined studies in PubMed, Web of
      Science, CNKI Scholar and WanFang databases from inception to January 2017.
      Papers were selected by inclusion and exclusion criteria in the context. Random
      effect meta-analysis estimated adherence. RESULTS: 22 studies were found by the
      inclusion criteria, which involved 1 37 699 patients with gout. Four ways to
      define adherence were reported. Meta-analysis revealed that the overall adherence
      rate was 47% (95% CI 42% to 52%, I2=99.7%). Adherence rate to ULT was 42% (95% CI
      37% to 47%, I2=99.8%) for prescription claims, 71% (95% CI 63% to 79%) for pill
      count, 66% (95% CI 50% to 81%, I2=86.3%) for self-report and 63% (95% CI 42% to
      83%, I2=82.9%) for interview, respectively. The influential factor on adherence
      rate was country of origin. CONCLUSIONS: Among adult patients with gout, overall
      adherence rate to ULT was as low as 47%, which suggested that clinicians should
      pay more attention to medication adherence in patients with gout to effectively
      improve adherence to ULT.

PMID- 29643151
TI  - Fruit and vegetable intake and body adiposity among populations in Eastern
      Canada: the Atlantic Partnership for Tomorrow's Health Study.
AB  - OBJECTIVES: The prevalence of obesity among populations in the Atlantic provinces
      is the highest in Canada. Some studies suggest that adequate fruit and vegetable
      consumption may help body weight management. We assessed the associations between
      fruit and vegetable intake with body adiposity among individuals who participated
      in the baseline survey of the Atlantic Partnership for Tomorrow's Health
      (Atlantic PATH) cohort study. METHODS: We carried out a cross-sectional analysis
      among 26 340 individuals (7979 men and 18 361 women) aged 35-69 years who were
      recruited in the baseline survey of the Atlantic PATH study. Data on fruit and
      vegetable intake, sociodemographic and behavioural factors, chronic disease,
      anthropometric measurements and body composition were included in the analysis.
      RESULTS: In the multivariable regression analyses, 1 SD increment of total fruit
      and vegetable intake was inversely associated with body mass index (-0.12 kg/m2;
      95% CI -0.19 to -0.05), waist circumference (-0.40 cm; 95% CI -0.58 to -0.23),
      percentage fat mass (-0.30%; 95% CI -0.44 to -0.17) and fat mass index (-0.14
      kg/m2; 95% CI -0.19 to -0.08). Fruit intake, but not vegetable intake, was
      consistently inversely associated with anthropometric indices, fat mass, obesity
      and abdominal obesity. CONCLUSIONS: Fruit and vegetable consumption was inversely
      associated with body adiposity among the participant population in Atlantic
      Canada. This association was primarily attributable to fruit intake. Longitudinal
      studies and randomised trials are warranted to confirm these observations and
      investigate the underlying mechanisms.

PMID- 29643152
TI  - Refugee maternal and perinatal health in Ontario, Canada: a retrospective
      population-based study.
AB  - OBJECTIVES: Immigrants are thought to be healthier than their native-born
      counterparts, but less is known about the health of refugees or forced migrants.
      Previous studies often equate refugee status with immigration status or country
      of birth (COB) and none have compared refugee to non-refugee immigrants from the
      same COB. Herein, we examined whether: (1) a refugee mother experiences greater
      odds of adverse maternal and perinatal health outcomes compared with a similar
      non-refugee mother from the same COB and (2) refugee and non-refugee immigrants
      differ from Canadian-born mothers for maternal and perinatal outcomes. DESIGN:
      This is a retrospective population-based database study. We implemented two
      cohort designs: (1) 1:1 matching of refugees to non-refugee immigrants on COB,
      year and age at arrival (+/-5 years) and (2) an unmatched design using all data.
      SETTING AND PARTICIPANTS: Refugee immigrant mothers (n=34 233), non-refugee
      immigrant mothers (n=243 439) and Canadian-born mothers (n=615 394) eligible for
      universal healthcare insurance who had a hospital birth in Ontario, Canada,
      between 2002 and 2014. PRIMARY OUTCOMES: Numerous adverse maternal and perinatal
      health outcomes. RESULTS: Refugees differed from non-refugee immigrants most
      notably for HIV, with respective rates of 0.39% and 0.20% and an adjusted OR
      (AOR) of 1.82 (95% CI 1.19 to 2.79). Other elevated outcomes included caesarean
      section (AOR 1.04, 95% CI 1.00 to 1.08) and moderate preterm birth (AOR 1.08, 95%
      CI 0.99 to 1.17). For the majority of outcomes, refugee and non-refugee
      immigrants experienced similar AORs when compared with Canadian-born mothers.
      CONCLUSIONS: Refugee status was associated with a few adverse maternal and
      perinatal health outcomes, but the associations were not strong except for HIV.
      The definition of refugee status used herein may not sensitively identify
      refugees at highest risk. Future research would benefit from further refining
      refugee status based on migration experiences.

PMID- 29643153
TI  - Incidence rate of community-acquired pneumonia in adults: a population-based
      prospective active surveillance study in three cities in South America.
AB  - OBJECTIVE: To determine the incidence rate and mortality of community-acquired
      pneumonia (CAP) in adults in three cities in Latin America during a 3-year
      period. DESIGN: Prospective population-based surveillance study. SETTING:
      Healthcare facilities (outpatient centres and hospitals) in the cities of General
      Roca (Argentina), Rivera (Uruguay) and Concepcion (Paraguay). PARTICIPANTS: 2302
      adults aged 18 years and older with CAP were prospectively enrolled between
      January 2012 and March 2015. MAIN OUTCOME MEASURES: Incidence rates of CAP in
      adults, predisposing conditions for disease, mortality at 14 days and at 1 year
      were estimated. Incidence rate of CAP, within each age group, was calculated by
      dividing the number of cases by the person-years of disease-free exposure time
      based on the last census; incidence rates were expressed per 1000 person-years.
      RESULTS: Median age of participants was 66 years, 46.44% were men, 68% were
      hospitalised. Annual incidence rate was 7.03 (95% CI 6.64 to 7.44) per 1000
      person-years in General Roca, 6.33 (95% CI 5.92 to 6.78) per 1000 person-years in
      Rivera and 1.76 (95% CI 1.55 to 2.00) per 1000 person-years in Concepcion.
      Incidence rates were highest in participants aged over 65 years. 82.4% had at
      least one predisposing condition and 48% had two or more (multimorbidity).
      Chronic heart disease (43.6%) and smoking (37.3%) were the most common risk
      factors. 14-day mortality rate was 12.1% and 1-year mortality was 24.9%.
      Multimorbidity was associated with an increased risk of death at 14 days (OR
      2.91; 95% CI 2.23 to 3.80) and at 1 year (OR 3.00; 95% CI 2.44 to 3.70).
      CONCLUSIONS: We found a high incidence rate of CAP in adults, ranging from 1.76
      to 7.03 per 1000 person-years, in three cities in South America, disclosing the
      high burden of disease in the region. Efforts to improve prevention strategies
      are needed.

PMID- 29643154
TI  - Associations between preoperative Oxford hip and knee scores and costs and
      quality of life of patients undergoing primary total joint replacement in the NHS
      England: an observational study.
AB  - OBJECTIVES: To assess how costs and quality of life (measured by EuroQoL-5
      Dimensions (EQ-5D)) before and after total hip replacement (THR) and total knee
      replacement (TKR) vary with age, gender and preoperative Oxford hip score (OHS)
      and Oxford knee score (OKS). DESIGN: Regression analyses using prospectively
      collected data from clinical trials, cohort studies and administrative data
      bases. SETTING: UK secondary care. PARTICIPANTS: Men and women undergoing primary
      THR or TKR. The Hospital Episode Statistics data linked to patient-reported
      outcome measures included 602 176 patients undergoing hip or knee replacement who
      were followed up for up to 6 years. The Knee Arthroplasty Trial included 2217
      patients undergoing TKR who were followed up for 12 years. The Clinical Outcomes
      in Arthroplasty Study cohort included 806 patients undergoing THR and 484
      patients undergoing TKR who were observed for 1 year. OUTCOME MEASURES: EQ-5D-3L
      quality of life before and after surgery, costs of primary arthroplasty, costs of
      revision arthroplasty and the costs of hospital readmissions and ambulatory costs
      in the year before and up to 12 years after joint replacement. RESULTS: Average
      postoperative utility for patients at the 5th percentile of the OHS/OKS
      distribution was 0.61/0.5 for THR/TKR and 0.89/0.85 for patients at the 95th
      percentile. The difference between postoperative and preoperative EQ-5D utility
      was highest for patients with preoperative OHS/OKS lower than 10. However,
      postoperative EQ-5D utility was higher than preoperative utility for all patients
      with OHS<=46 and those with OKS<=44. In contrast, costs were generally higher for
      patients with low preoperative OHS/OKS than those with high OHS/OKS. For example,
      costs of hospital readmissions within 12 months after primary THR/TKR were
      L740/L888 for patients at the 5th percentile compared with L314/L404 at the 95th
      percentile of the OHS/OKS distribution. CONCLUSIONS: Our findings suggest that
      costs and quality of life associated with total joint replacement vary
      systematically with preoperative symptoms measured by OHS/OKS.

PMID- 29643155
TI  - Femoral Nerve Block Intervention in Neck of Femur Fracture (FINOF): a randomised
      controlled trial.
AB  - OBJECTIVE: Fractured neck of femur is a severely painful condition with
      significant mortality and morbidity. We investigated whether early and continuous
      use of femoral nerve block can improve pain on movement and mobility after
      surgery in older participants with fragility neck of femur fracture. DESIGN:
      Prospective single-centre, randomised controlled pragmatic trial. SETTING:
      Secondary care, acute National Health Service Trust, UK. PARTICIPANTS:
      Participants admitted with a history and examination suggesting fractured neck of
      femur. INTERVENTION: Immediate continuous femoral nerve block via catheter or
      standard analgesia. OUTCOME MEASURES: Primary outcome measures were Cumulative
      Dynamic Pain score and Cumulated Ambulation Score from surgery until day 3
      postoperatively. Secondary outcome measures included pain scores at rest,
      cumulative side effects (nausea and constipation), quality of life (measured by
      EuroQOL 5 D instrument (EQ-5D) score) at day 3 and day 30, and rehabilitation
      outcome (measured by mobility score). RESULTS: 141 participants were recruited,
      with 23 excluded. No significant difference was detected between Cumulative
      Dynamic Pain Score (standard care (n=56) vs intervention (n=55) 20 (IQR 15-24) vs
      20 (15-23), p=0.51) or Cumulated Ambulation Score (standard care vs intervention
      6 (5-9) vs 7 (5-10), p=0.76). There were no statistically different differences
      in secondary outcomes except cumulative pain at rest: 5 (0.5-6.5) in the standard
      care group and 2 (0-5) in the intervention group (p=0.043). CONCLUSIONS: Early
      application of continuous femoral nerve block compared with standard systemic
      analgesia did not result in improved dynamic pain score or superior postoperative
      ambulation. This technique may provide superior pain relief at rest. Continuous
      femoral nerve block did not delay initial control of pain or mobilisation after
      surgery. TRIAL REGISTRATION NUMBER: ISRCTN92946117; Pre-results.

PMID- 29643157
TI  - Minimum pupil in pupillary response to light and myopia affect disk halo size: a
      cross-sectional study.
AB  - OBJECTIVES: To evaluate the relationship between pupillary response to light,
      myopia and disk halo size. DESIGN: Cross-sectional study. SETTING: Single
      refractive surgery centre. PARTICIPANTS: In this study, 197 right eyes of 197
      patients between 20 and 35 years of age were evaluated for disk halo size and
      pupillary response to light with a vision monitor. PRIMARY AND SECONDARY OUTCOME
      MEASURES: Halo radius, age, spherical equivalent (SE), axial length (AL), initial
      diameter, amplitude of contraction, latency of contraction, duration of
      contraction, velocity of contraction, latency of dilation, duration of dilation,
      velocity of dilation, maximum pupil, minimum pupil, average pupil and dark pupil.
      RESULTS: Significant associations were found between disk halo size and SE (r=
      0.219, P=0.002), AL (r=0.152, P=0.033) and minimum pupil (r=0.149, P=0.037).
      There were no associations between disk halo size and initial diameter, amplitude
      of contraction, latency of contraction, duration of contraction, velocity of
      contraction, latency of dilation, duration of dilation, velocity of dilation,
      maximum pupil, average pupil, dark pupil and age (P>0.05). A significant
      difference in disk halo size was detected between the low-moderate and high
      myopia (SE< -6 D) groups (P=0.002) and between the small and large (minimum
      pupil>=4 mm) minimum pupil size groups (P=0.014). CONCLUSIONS: Patients with a
      high SE and large minimum pupil size (minimum pupil >=4 mm) suffered more
      disability glare than those with a low SE and small minimum pupil size.

PMID- 29643156
TI  - IndEcho study: cohort study investigating birth size, childhood growth and young
      adult cardiovascular risk factors as predictors of midlife myocardial structure
      and function in South Asians.
AB  - INTRODUCTION: South Asians have high rates of cardiovascular disease (CVD) and
      its risk factors (hypertension, diabetes, dyslipidaemia and central obesity).
      Left ventricular (LV) hypertrophy and dysfunction are features of these disorders
      and important predictors of CVD mortality. Lower birth and infant weight and
      greater childhood weight gain are associated with increased adult CVD mortality,
      but there are few data on their relationship to LV function. The IndEcho study
      will examine associations of birth size, growth during infancy, childhood and
      adolescence and CVD risk factors in young adulthood with midlife cardiac
      structure and function in South Asian Indians. METHODS AND ANALYSIS: We propose
      to study approximately 3000 men and women aged 43-50 years from two birth cohorts
      established in 1969-1973: the New Delhi Birth Cohort (n=1508) and Vellore Birth
      Cohort (n=2156). They had serial measurements of weight and height from birth to
      early adulthood. CVD risk markers (body composition, blood pressure, glucose
      tolerance and lipids) and lifestyle characteristics (tobacco and alcohol
      consumption, physical activity, socioeconomic status) were assessed at age ~30
      years. Clinical measurements in IndEcho will include anthropometry, blood
      pressure, biochemistry (glucose, fasting insulin and lipids, urinary
      albumin/creatinine ratio) and body composition by dual energy X-ray
      absorptiometry and bioelectrical impedance. Outcomes are LV mass and indices of
      LV systolic and diastolic function assessed by two-dimensional and Doppler
      echocardiography, carotid intimal-media thickness and ECG indicators of
      ischaemia. Regression and conditional growth models, adjusted for potential
      confounders, will be used to study associations of childhood and young adult
      exposures with these cardiovascular outcomes. ETHICS AND DISSEMINATION: The study
      has been approved by the Health Ministry Steering Committee, Government of India
      and institutional ethics committees of participating centres in India and the
      University of Southampton, UK. Results will be disseminated through scientific
      meetings and peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN13432279;
      Pre-results.

PMID- 29643158
TI  - Is an enhanced behaviour change intervention cost-effective compared with
      physiotherapy for patients with chronic low back pain? Results from a multicentre
      trial in Israel.
AB  - OBJECTIVE: To assess the cost-effectiveness of an enhanced transtheoretical model
      of behaviour change in conjunction with physiotherapy compared with standard care
      (physiotherapy) in patients with chronic lower back pain (CLBP). DESIGN: Cost
      utility and cost-effectiveness analyses alongside a multicentre controlled trial
      from a healthcare perspective with a 1-year time horizon. SETTING: The trial was
      conducted in eight centres within the Sharon district in Israel. PARTICIPANTS:
      220 participants aged between 25 and 55 years who suffered from CLBP for a
      minimum of 3 months were recruited. INTERVENTIONS: The intervention used a model
      of behaviour change that sought to increase the adherence and implementation of
      physical activity in conjunction with physiotherapy. The control arm received
      standard care in the form of physiotherapy. PRIMARY AND SECONDARY MEASURES: The
      primary outcome was the incremental cost per quality-adjusted life year (QALY) of
      the intervention arm compared with standard care. The secondary outcome was the
      incremental cost per Roland-Morris Disability Questionnaire point. RESULTS: The
      cost per QALY point estimate was 10 645 New Israeli shekels (NIS) (L1737.11).
      There was an 88% chance the intervention was cost-effective at NIS50 000 per QALY
      threshold. Excluding training costs, the intervention dominated the control arm,
      resulting in fewer physiotherapy and physician visits while improving outcomes.
      CONCLUSIONS: The enhanced transtheoretical model intervention appears to be a
      very cost-effective intervention leading to improved outcomes for low cost. Given
      limitations within this study, there is justification for examining the
      intervention within a larger, long-term randomised controlled trial. TRIAL
      REGISTRATION NUMBER: NCT01631344; Pre-results.

PMID- 29643159
TI  - Role of iodine-containing multivitamins during pregnancy for children's brain
      function: protocol of an ongoing randomised controlled trial: the SWIDDICH study.
AB  - INTRODUCTION: Iodine is essential for normal brain development. Moderate and
      severe fetal iodine deficiency results in substantial to serious developmental
      delay in children. Mild iodine deficiency in pregnancy is associated with
      neurodevelopmental deficits in the offspring, but evidence from randomised trials
      is lacking. The aim of the Swedish Iodine in Pregnancy and Development in
      Children study is to determine the effect of daily supplementation with 150 ug
      iodine during pregnancy on the offspring's neuropsychological development up to
      14 years of age. METHODS AND ANALYSIS: Thyroid healthy pregnant women (n=1275:
      age range 18-40 years) at <=12 weeks gestation will be randomly assigned to
      receive multivitamin supplements containing 150 ug iodine or non-iodine
      containing multivitamin daily throughout pregnancy. As a primary outcome, IQ will
      be measured in the offspring at 7 years (Wechsler Intelligence Scale for Children
      V). As secondary outcomes, IQ will be measured at 3.5 and 14 years, psychomotor
      development at 18 months and 7 years, and behaviour at 3.5, 7 and 14 years.
      Iodine status (urinary iodine concentration) will be measured during pregnancy
      and in the offspring at 3.5, 7 and 14 years. Thyroid function (thyroid hormones,
      thyroglobulin), and deiodinase type 2 polymorphisms will be measured during
      pregnancy and in the offspring at 7 and 14 years. Structural MRI or other
      relevant structural or functional brain imaging procedures will be performed in a
      subgroup of children at 7 and 14 years. Background and socioeconomic information
      will be collected at all follow-up times. ETHICS AND DISSEMINATION: This study is
      approved by the Ethics Committee in Goteborg, Sweden (Diary numbers: 431-12
      approved 18 June 2012 (pregnancy part) and 1089-16 approved 8 February 2017
      (children follow-up)). According to Swedish regulations, dietary supplements are
      governed by the National Food Agency and not by the Medical Product Agency.
      Therefore, there is no requirement for a monitoring committee and the National
      Food Agency does not perform any audits of trial conduct. The trial will be
      conducted in accordance with the Declaration of Helsinki. The participating sites
      will be contacted regarding important protocol changes, both orally and in
      writing, and the trial registry database will be updated accordingly. Study
      results will be presented at relevant conferences, and submitted to peer-reviewed
      journals with open access in the fields of endocrinology, paediatrics and
      nutrition. After the appropriate embargo period, the results will be communicated
      to participants, healthcare professionals at the maternal healthcare centres, the
      public and other relevant groups, such as the national guideline group for
      thyroid and pregnancy and the National Food Agency. TRIAL REGISTRATION NUMBER:
      NCT02378246; Pre-results.

PMID- 29643160
TI  - Using machine learning techniques to develop forecasting algorithms for
      postoperative complications: protocol for a retrospective study.
AB  - INTRODUCTION: Mortality and morbidity following surgery are pressing public
      health concerns in the USA. Traditional prediction models for postoperative
      adverse outcomes demonstrate good discrimination at the population level, but the
      ability to forecast an individual patient's trajectory in real time remains poor.
      We propose to apply machine learning techniques to perioperative time-series data
      to develop algorithms for predicting adverse perioperative outcomes. METHODS AND
      ANALYSIS: This study will include all adult patients who had surgery at our
      tertiary care hospital over a 4-year period. Patient history, laboratory values,
      minute-by-minute intraoperative vital signs and medications administered will be
      extracted from the electronic medical record. Outcomes will include in-hospital
      mortality, postoperative acute kidney injury and postoperative respiratory
      failure. Forecasting algorithms for each of these outcomes will be constructed
      using density-based logistic regression after employing a Nadaraya-Watson kernel
      density estimator. Time-series variables will be analysed using first and second
      order feature extraction, shapelet methods and convolutional neural networks. The
      algorithms will be validated through measurement of precision and recall. ETHICS
      AND DISSEMINATION: This study has been approved by the Human Research Protection
      Office at Washington University in St Louis. The successful development of these
      forecasting algorithms will allow perioperative healthcare clinicians to predict
      more accurately an individual patient's risk for specific adverse perioperative
      outcomes in real time. Knowledge of a patient's dynamic risk profile may allow
      clinicians to make targeted changes in the care plan that will alter the
      patient's outcome trajectory. This hypothesis will be tested in a future
      randomised controlled trial.

PMID- 29643161
TI  - The Collaborative IPD of Sleep and Stillbirth (Cribss): is maternal going-to
      sleep position a risk factor for late stillbirth and does maternal sleep position
      interact with fetal vulnerability? An individual participant data meta-analysis
      study protocol.
AB  - INTRODUCTION: Accumulating evidence has shown an association between maternal
      supine going-to-sleep position and stillbirth in late pregnancy. Advising women
      not to go-to-sleep on their back can potentially reduce late stillbirth rate by
      9%. However, the association between maternal right-sided going-to-sleep position
      and stillbirth is inconsistent across studies. Furthermore, individual studies
      are underpowered to investigate interactions between maternal going-to-sleep
      position and fetal vulnerability, which is potentially important for producing
      clear and tailored public health messages on safe going-to-sleep position. We
      will use individual participant data (IPD) from existing studies to assess
      whether right-side and supine going-to-sleep positions are independent risk
      factors for late stillbirth and to test the interaction between going-to-sleep
      position and fetal vulnerability. METHODS AND ANALYSIS: An IPD meta-analysis
      approach will be used using the Cochrane Collaboration-endorsed methodology. We
      will identify case-control and prospective cohort studies and randomised trials
      which collected maternal going-to-sleep position data and pregnancy outcome data
      that included stillbirth. The primary outcome is stillbirth. A one stage
      procedure meta-analysis, stratified by study with adjustment of a priori
      confounders will be carried out. ETHICS AND DISSEMINATION: The IPD meta-analysis
      has obtained central ethics approval from the New Zealand Health and Disability
      Ethics Committee, ref: NTX/06/05/054/AM06. Individual studies should also have
      ethical approval from relevant local ethics committees. Interpretation of the
      results will be discussed with consumer representatives. Results of the study
      will be published in peer-reviewed journals and presented at international
      conferences. PROSPERO REGISTRATION NUMBER: CRD42017047703.

PMID- 29643162
TI  - What attributions do Australian high-performing general practices make for their
      success? Applying the clinical microsystems framework: a qualitative study.
AB  - OBJECTIVES: To identify the success attributions of high-performing Australian
      general practices and the enablers and barriers they envisage for practices
      wishing to emulate them. DESIGN: Qualitative study using semi-structured
      interviews and content analysis of the data. Responses were recorded, transcribed
      verbatim and coded according to success characteristics of high-performing
      clinical microsystems. SETTING: Primary healthcare with the participating general
      practices representing all Australian states and territories, and representing
      metropolitan and rural locations. PARTICIPANTS: Twenty-two general practices
      identified as high performing via a number of success criteria. The 52
      participants were 19 general practitioners, 18 practice managers and 15 practice
      nurses. RESULTS: Participants most frequently attributed success to the
      interdependence of the team members, patient-focused care and leadership of the
      practice. They most often signalled practice leadership, team interdependence and
      staff focus as enablers that other organisations would need to emulate their
      success. They most frequently identified barriers that might be encountered in
      the form of potential deficits or limitations in practice leadership, staff focus
      and mesosystem support. CONCLUSIONS: Practice leaders need to empower their teams
      to take action through providing inclusive leadership that facilitates team
      interdependence. Mesosystem support for quality improvement in general practice
      should focus on enabling this leadership and team building, thereby ensuring
      improvement efforts are converted into effective healthcare provision.

PMID- 29643163
TI  - Effect of intratracheal dexmedetomidine administration on recovery from general
      anaesthesia after gynaecological laparoscopic surgery: a randomised double
      blinded study.
AB  - OBJECTIVES: To examine the efficacy of intratracheal dexmedetomidine (Dex)
      injection for the prevention of the laryngeal response on emergence from general
      anaesthesia following gynaecological laparoscopic surgery. DESIGN: Prospective,
      randomised, double-blinded, controlled trial. SETTING: A general hospital,
      Guangdong Province, China. PARTICIPANTS: All patients who underwent elective
      laparoscopic gynaecological surgery, aged 18-60 years old, 40-80 kg in weight,
      American Society of Anesthesiologists class I-II were eligible. Patients were
      excluded if they had respiratory disease, heart disorders which might represent
      risk factors of potential complications of Dex such as bradycardia, heart block,
      coronary heart disease, uncontrolled hypertension or the long-term use of
      sedative drugs. INTERVENTION: Patients were randomly allocated to either receive
      intratracheal Dex (DT), intravenous Dex (DV) or intravenous saline (CON, n=30,
      respectively). In the DT and DV groups, Dex (0.5 ug/kg) was diluted and mixed in
      1 or 20 mL of saline, respectively, and injected via the intratracheal or
      intravenous route 30 min before the completion of the surgery. OUTCOME MEASURES:
      The primary outcome was the coughing extent among the three groups. Secondary
      outcomes included awareness time, extubation time, postoperative visual analogue
      scale and Steward recovery score. RESULTS: Compared with the CON group, the
      extent of coughing was significantly reduced in both the DV group and the DT
      group. Furthermore, the mean time to awareness (13.4 (4.3) vs 8.8 (2.9), p<0.001)
      and the extubation time (14.3 (4.3) vs 8.4 (3.6), p<0.001) were reduced in the DT
      group. Patients in the DT group also experienced better early recovery quality
      and less pain than those in the CON group. Furthermore, intratracheal Dex
      administration contributed to improved stability in haemodynamics with no
      significant side effects. CONCLUSIONS: Intratracheal Dex administration may avoid
      untoward laryngeal responses for patients emerging from general anaesthesia after
      gynaecological laparoscopy. TRIAL REGISTRATION NUMBER: ChiCTR-IOR-15007611.

PMID- 29643164
TI  - Complications in breast augmentation with textured versus smooth breast implants:
      a systematic review protocol.
AB  - INTRODUCTION: Breast augmentation is one of the most popular aesthetic plastic
      surgeries worldwide. There are various types of breast implants, and these can be
      categorised into different broad groups based on their content, shape or surface,
      to name a few. When looking at the surface of the shell, they can be categorised
      into two main kinds: textured and smooth implants. To our knowledge, a literature
      review and meta-analysis of the complications of these two types of implants when
      used for aesthetic breast augmentation has yet to be written. METHODS AND
      ANALYSIS: The PubMed, EMBASE and Cochrane electronic databases will be searched
      from their inception to 1 October 2017. Only cohort studies, case series, case
      control studies and randomised controlled trials will be included. Identification
      of the articles for inclusion will be carried out by two independent researchers,
      and data will be extracted from these studies for analysis. This protocol defines
      the inclusion and exclusion criteria, as well as the primary and secondary
      outcomes. Statistical data analysis will be conducted in Review Manager V.5.3
      from Cochrane Collaboration. The methodological quality of the included studies
      will also be assessed. ETHICS AND DISSEMINATION: This review will analyse
      secondary data collected from studies which are not linked to any specific
      individual. Once completed, the conclusions of the review could prove to be a
      valuable resource for plastic surgeons to conduct aesthetic implant procedures.
      The review will be submitted for publication in a peer-reviewed journal and
      presented at various national and international conferences. PROSPERO
      REGISTRATION NUMBER: CRD42017078727.

PMID- 29643165
TI  - Reoperation after breast-conserving surgery for cancer in Australia: statewide
      cohort study of linked hospital data.
AB  - OBJECTIVES: To investigate between-hospital variation in the probability of
      reoperation within 90 days of initial breast-conserving surgery (BCS), and the
      contribution of health system-level and other factors. DESIGN: Population-based,
      retrospective cohort study. SETTING: New South Wales (NSW), Australia.
      PARTICIPANTS: Linked administrative hospitalisation data were used to define a
      cohort of adult women undergoing initial BCS for breast cancer in NSW between 1
      July 2002 and 31 December 2013. PRIMARY OUTCOME MEASURES: Multilevel, cross
      classified models with patients clustered within hospitals and residential areas
      were used to examine factors associated with any reoperation, and either re
      excision or mastectomy, within 90 days. RESULTS: Of 34 458 women undergoing BCS,
      29.1% underwent reoperation within 90 days, half of which were mastectomies.
      Overall, the probability of reoperation decreased slightly over time. However,
      there were divergent patterns by reoperation type; the probability of re-excision
      increased alongside a concomitant decrease in the probability of mastectomy.
      Significant between-hospital variation was observed. Non-metropolitan location
      and surgery at low-volume hospitals were associated with a higher overall
      probability of reoperation, and of mastectomy specifically, after accounting for
      patient-level factors, calendar year and area-level socioeconomic status. The
      magnitude of association with geographical location and surgical volume decreased
      over time. CONCLUSIONS: Reoperation rates within 90 days of BCS varied
      significantly between hospitals. For women undergoing mastectomy after BCS, this
      represents a dramatic change in clinical course. Multilevel modelling suggests
      unwarranted clinical variation may be an issue, likely due to disparities in
      access to multidisciplinary breast cancer care and preoperative diagnostic
      procedures. However, the observed reduction in disparities over time is
      encouraging and indicates that guidelines and policy initiatives have the
      potential to improve regional breast cancer care.

PMID- 29643166
TI  - Metabolic syndrome and its components with neuron-specific enolase: a cross
      sectional study in large health check-up population in China.
AB  - OBJECTIVE: This study was aimed at investigating the relationship between neuron
      specific enolase (NSE) and components of metabolic syndrome (MS). DESIGN: Cross
      sectional study. SETTING: Chinese health check-up population. PARTICIPANTS: 40
      684 health check-up people were enrolled in this study from year 2014 to 2016.
      MAIN OUTCOME MEASURES: OR and coefficient for MS. RESULTS: The percentage of
      abnormal NSE and MS was 26.85% and 8.85%, respectively. There were significant
      differences in sex, body mass index, drinking habit, triglycerides (TGs), high
      density lipoprotein cholesterol (HDL-C), blood pressure and MS between low-NSE
      and high-NSE groups. In logistic regression analysis, elevated NSE was present in
      MS, higher body mass index, hypertriglyceridaemia, hypertension and low-HDL
      groups. Stepwise linear analysis showed a negative correlation between NSE and
      fasting blood glucose (FBG) (<6.0 mmol/L), and a positive correlation between NSE
      and TGs (<20 mmol/L), systolic blood pressure (75-200 mm Hg), HDL-C (0.75-2.50
      mmol/L), diastolic blood pressure (<70 mm Hg) and FBG (6.00-20.00 mmol/L).
      Furthermore, MS was positively correlated with NSE within the range of 2.00-7.50
      ng/mL, but had a negative correlation with NSE within the range of 7.50-23.00
      ng/mL. CONCLUSION: There are associations between NSE with MS and its components.
      The result suggests that NSE may be a potential predictor of MS. Further research
      could be conducted in discussing the potential mechanism involved.

PMID- 29643167
TI  - Behaviours preceding suicides at railway and underground locations: a
      multimethodological qualitative approach.
AB  - OBJECTIVES: Suicides by train have devastating consequences for families, the
      rail industry, staff dealing with the aftermath of such incidents and potential
      witnesses. To reduce suicides and suicide attempts by rail, it is important to
      learn how safe interventions can be made. However, very little is known about how
      to identify someone who may be about to make a suicide attempt at a railway
      location (including underground/subways). The current research employed a novel
      way of understanding what behaviours might immediately precede a suicide or
      suicide attempt at these locations. DESIGN AND METHODS: A qualitative thematic
      approach was used for three parallel studies. Data were gathered from several
      sources, including interviews with individuals who survived a rail suicide
      attempt (n=9), CCTV footage of individuals who died by rail suicide (n=16) and
      qualitative survey data providing views from rail staff (n=79). RESULTS: Our
      research suggests that there are several behaviours that people may carry out
      before a suicide or suicide attempt at a rail location, including station hopping
      and platform switching, limiting contact with others, positioning themselves at
      the end of the track where the train/tube approaches, allowing trains to pass by
      and carrying out repetitive behaviours. CONCLUSIONS: There are several behaviours
      that may be identifiable in the moments leading up to a suicide or suicide
      attempt on the railways which may present opportunities for intervention. These
      findings have implications for several stakeholders, including rail providers,
      transport police and other organisations focused on suicide prevention.

PMID- 29643168
TI  - Fatigue in patients with chronic obstructive pulmonary disease: protocol of the
      Dutch multicentre, longitudinal, observational FAntasTIGUE study.
AB  - INTRODUCTION: Fatigue is the second most common symptom in patients with chronic
      obstructive pulmonary disease (COPD). Despite its high prevalence, fatigue is
      often ignored in daily practice. For this reason, little is known about the
      underlying determinants of fatigue in patients with COPD. The primary objectives
      of this study are to chart the course of fatigue in patients with COPD, to
      identify the physical, systemic, psychological and behavioural factors that
      precipitate and perpetuate fatigue in patients with COPD, to evaluate the impact
      of exacerbation-related hospitalisations on fatigue and to better understand the
      association between fatigue and 2-year all-cause hospitalisation and mortality in
      patients with COPD. The secondary aim is to identify diurnal differences in
      fatigue by using ecological momentary assessment (EMA). This manuscript describes
      the protocol of the FAntasTIGUE study and gives an overview of the possible
      strengths, weaknesses and clinical implications. METHODS AND ANALYSIS: A 2-year
      longitudinal, observational study, enrolling 400 patients with clinically stable
      COPD has been designed. Fatigue, the primary outcome, will be measured by the
      subjective fatigue subscale of the Checklist Individual Strength (CIS-Fatigue).
      The secondary outcome is the day-to-day/diurnal fatigue, registered in a
      subsample (n=60) by EMA. CIS-Fatigue and EMA will be evaluated at baseline, and
      at 4, 8 and 12 months. The precipitating and perpetuating factors of fatigue
      (physical, psychological, behavioural and systemic) will be assessed at baseline
      and at 12 months. Additional assessments will be conducted following
      hospitalisation due to an exacerbation of COPD that occurs between baseline and
      12 months. Finally, at 18 and 24 months the participants will be followed up on
      their fatigue, number of exacerbations, exacerbation-related hospitalisation and
      survival. ETHICS AND DISSEMINATION: This protocol was approved by the Medical
      research Ethics Committees United, Nieuwegein, the Netherlands (NL60484.100.17).
      TRIAL REGISTRATION NUMBER: NTR6933; Pre-results.

PMID- 29643169
TI  - Safety and feasibility evaluation of tourniquets for total knee replacement (SAFE
      TKR): study protocol.
AB  - INTRODUCTION: This study is designed to determine whether a full randomised
      controlled trial (RCT) examining the clinical effectiveness and safety of total
      knee replacement surgery with or without a tourniquet is warranted and feasible.
      METHOD AND ANALYSIS: Single centre, patient-blinded and assessor-blinded RCT. A
      computer-generated randomisation service will allocate 50 participants into one
      of two trial treatments, surgery with or without a tourniquet. The primary
      objective is to estimate recruitment, crossovers and follow-up of patients. All
      patients will have an MRI scan of their brain preoperatively and day 1 or 2
      postoperatively to identify ischaemic cerebral emboli (primary clinical outcome).
      Oxford Cognitive Screen, Montreal Cognitive Assessment and Mini-Mental State
      Examination will be evaluated as outcome tools for measuring cognitive impairment
      at days 1, 2 and 7 postoperatively. Thigh pain, blood transfusion requirements,
      venous thromboembolism, revision surgery, surgical complications, mortality and
      Oxford knee and five-level EuroQol-5D scores will be collected over 12 months.
      Integrated qualitative research study: 30 trial patients and 20 knee surgeons
      will take part in semistructured interviews. Interviews will capture views
      regarding the pilot trial and explore barriers and potential solutions to a full
      trial. Multicentre cohort study: UK National Joint Registry data will be linked
      to Hospital Episode Statistics to estimate the relationship between tourniquet
      use and venous thromboembolic event, length of hospital stay, risk of revision
      surgery and death. The study will conclude with a multidisciplinary workshop to
      reach a consensus on whether a full trial is warranted and feasible. ETHICS AND
      DISSEMINATION: National Research Ethics Committee (West Midlands-Edgbaston)
      approved this study on 27 January 2016 (15/WM/0455). The study is sponsored by
      University of Warwick and University Hospitals Coventry and Warwickshire. The
      results will be disseminated via high-impact peer-reviewed publication. TRIAL
      REGISTRATION NUMBER: ISRCTN20873088; Pre-results.

PMID- 29643170
TI  - Treatment options in idiopathic subglottic stenosis: protocol for a prospective
      international multicentre pragmatic trial.
AB  - INTRODUCTION: Idiopathic subglottic stenosis (iSGS) is an unexplained progressive
      obstruction of the upper airway that occurs almost exclusively in adult,
      Caucasian women. The disease is characterised by mucosal inflammation and
      localised fibrosis resulting in life-threatening blockage of the upper airway.
      Because of high recurrence rates, patients with iSGS will frequently require
      multiple procedures following their initial diagnosis. Both the disease and its
      therapies profoundly affect patients' ability to breathe, communicate and
      swallow. A variety of treatments have been advanced to manage this condition.
      However, comparative data on effectiveness and side effects of the unique
      approaches have never been systematically evaluated. This study will create an
      international, multi-institutional prospective cohort of patients with iSGS. It
      will compare three surgical approaches to determine how well the most commonly
      used treatments in iSGS 'work' and what quality of life (QOL) trade-offs are
      associated with each approach. METHODS AND ANALYSIS: A prospective pragmatic
      trial comparing the 'Standard of Care' for iSGS at multiple international
      institutions. Patients with a diagnosis of iSGS without clinical or laboratory
      evidence of vasculitis or a history of endotracheal intubation 2 years prior to
      symptom onset will be included in the study. Prospective evaluation of disease
      recurrence requiring operative intervention, validated patient-reported outcome
      (PRO) measures as well as patient-generated health data (mobile peak flow
      recordings and daily steps taken) will be longitudinally tracked for 36 months.
      The primary endpoint is treatment effectiveness defined as time to recurrent
      operative procedure. Secondary endpoints relate to treatment side effects and
      include PRO measures in voice, swallowing, breathing and global QOL as well as
      patient-generated health data. ETHICS AND DISSEMINATION: This protocol was
      approved by the local IRB Committee of the Vanderbilt University Medical Center
      in July 2015. The findings of the trial will be disseminated through peer
      reviewed journals, national and international conference presentations and
      directly to patient with iSGS via social media-based support groups. TRIAL
      REGISTRATION NUMBER: NCT02481817.

PMID- 29643173
TI  - --Mitochondrial ATP synthase dimers spontaneously associate due to a long-range
      membrane-induced force.
AB  - Adenosine triphosphate (ATP) synthases populate the inner membranes of
      mitochondria, where they produce the majority of the ATP required by the cell.
      From yeast to vertebrates, cryoelectron tomograms of these membranes have
      consistently revealed a very precise organization of these enzymes. Rather than
      being scattered throughout the membrane, the ATP synthases form dimers, and these
      dimers are organized into rows that extend for hundreds of nanometers. The rows
      are only observed in the membrane invaginations known as cristae, specifically
      along their sharply curved edges. Although the presence of these macromolecular
      structures has been irrefutably linked to the proper development of cristae
      morphology, it has been unclear what drives the formation of the rows and why
      they are specifically localized in the cristae. In this study, we present a
      quantitative molecular-simulation analysis that strongly suggests that the dimers
      of ATP synthases organize into rows spontaneously, driven by a long-range
      attractive force that arises from the relief of the overall elastic strain of the
      membrane. The strain is caused by the V-like shape of the dimers, unique among
      membrane protein complexes, which induces a strong deformation in the surrounding
      membrane. The process of row formation is therefore not a result of direct
      protein-protein interactions or a specific lipid composition of the membrane. We
      further hypothesize that, once assembled, the ATP synthase dimer rows prime the
      inner mitochondrial membrane to develop folds and invaginations by causing
      macroscopic membrane ridges that ultimately become the edges of cristae. In this
      way, mitochondrial ATP synthases would contribute to the generation of a
      morphology that maximizes the surface area of the inner membrane, and thus ATP
      production. Finally, we outline key experiments that would be required to verify
      or refute this hypothesis.

PMID- 29643172
TI  - The syndromic deafness mutation G12R impairs fast and slow gating in Cx26
      hemichannels.
AB  - Mutations in connexin 26 (Cx26) hemichannels can lead to syndromic deafness that
      affects the cochlea and skin. These mutations lead to gain-of-function
      hemichannel phenotypes by unknown molecular mechanisms. In this study, we
      investigate the biophysical properties of the syndromic mutant Cx26G12R (G12R).
      Unlike wild-type Cx26, G12R macroscopic hemichannel currents do not saturate upon
      depolarization, and deactivation is faster during hyperpolarization, suggesting
      that these channels have impaired fast and slow gating. Single G12R hemichannels
      show a large increase in open probability, and transitions to the subconductance
      state are rare and short-lived, demonstrating an inoperative fast gating
      mechanism. Molecular dynamics simulations indicate that G12R causes a
      displacement of the N terminus toward the cytoplasm, favoring an interaction
      between R12 in the N terminus and R99 in the intracellular loop. Disruption of
      this interaction recovers the fast and slow voltage-dependent gating mechanisms.
      These results suggest that the mechanisms of fast and slow gating in connexin
      hemichannels are coupled and provide a molecular mechanism for the gain-of
      function phenotype displayed by the syndromic G12R mutation.

PMID- 29643174
TI  - Patterns of mitochondrial membrane remodeling parallel functional adaptations to
      thermal stress.
AB  - The effect of temperature on mitochondrial performance is thought to be partly
      due to its effect on mitochondrial membranes. Numerous studies have shown that
      thermal acclimation and adaptation can alter the amount of inner-mitochondrial
      membrane (IMM), but little is known about the capacity of organisms to modulate
      mitochondrial membrane composition. Using northern and southern subspecies of
      Atlantic killifish (Fundulus heteroclitus) that are locally adapted to different
      environmental temperatures, we assessed whether thermal acclimation altered liver
      mitochondrial respiratory capacity or the composition and amount of IMM. We
      measured changes in phospholipid headgroups and headgroup-specific fatty acid
      (FA) remodeling, and used respirometry to assess mitochondrial respiratory
      capacity. Acclimation to 5 degrees C and 33 degrees C altered mitochondrial
      respiratory capacity in both subspecies. Northern F. heteroclitus exhibited
      greater mitochondrial respiratory capacity across acclimation temperatures,
      consistent with previously observed subspecies differences in whole-organism
      aerobic metabolism. Mitochondrial phospholipids were altered following thermal
      acclimation, and the direction of these changes was largely consistent between
      subspecies. These effects were primarily driven by remodeling of specific
      phospholipid classes and were associated with shifts in metabolic phenotypes.
      There were also differences in membrane composition between subspecies that were
      driven largely by differences in phospholipid classes. Changes in respiratory
      capacity between subspecies and with acclimation were largely but not completely
      accounted for by alterations in the amount of IMM. Taken together, these results
      support a role for changes in liver mitochondrial function in the ectothermic
      response to thermal stress during both acclimation and adaptation, and implicate
      lipid remodeling as a mechanism contributing to these changes.

PMID- 29643175
TI  - Impaired associative learning after chronic exposure to pesticides in young adult
      honey bees.
AB  - Neonicotinoids are the most widespread insecticides in agriculture, preferred for
      their low toxicity to mammals and their systemic nature. Nevertheless, there have
      been increasing concerns regarding their impact on non-target organisms.
      Glyphosate is also widely used in crops and, therefore, traces of this pesticide
      are likely to be found together with neonicotinoids. Although glyphosate is
      considered a herbicide, adverse effects have been found on animal species,
      including honey bees. Apis mellifera is one of the most important pollinators in
      agroecosystems and is exposed to both these pesticides. Traces can be found in
      nectar and pollen of flowers that honey bees visit, but also in honey stores
      inside the hive. Young workers, which perform in-hive tasks that are crucial for
      colony maintenance, are potentially exposed to both these contaminated resources.
      These workers present high plasticity and are susceptible to stimuli that can
      modulate their behaviour and impact on colony state. Therefore, by performing
      standardised assays to study sublethal effects of these pesticides, these bees
      can be used as bioindicators. We studied the effect of chronic joint exposure to
      field-realistic concentrations of the neonicotinoid imidacloprid and glyphosate
      on gustatory perception and olfactory learning. Both pesticides reduced sucrose
      responsiveness and had a negative effect on olfactory learning. Glyphosate also
      reduced food uptake during rearing. The results indicate differential
      susceptibility according to honey bee age. The two agrochemicals had adverse
      effects on different aspects of honey bee appetitive behaviour, which could have
      repercussions for food distribution, propagation of olfactory information and
      task coordination within the nest.

PMID- 29643177
TI  - Should Hypertension Be Treated in Late Life to Preserve Cognitive Function? Pro
      Side of the Argument.

PMID- 29643179
TI  - Correction to: Cellular FLICE-Inhibitory Protein Protects Against Cardiac
      Remodeling Induced by Angiotensin II in Mice.

PMID- 29643178
TI  - Should Hypertension Be Treated in Late Life to Preserve Cognitive Function? Con
      Side of the Argument.

PMID- 29643180
TI  - Structural control of caspase-generated glutamyl-tRNA synthetase by appended
      noncatalytic WHEP domains.
AB  - Aminoacyl-tRNA synthetases are ubiquitous, evolutionarily conserved enzymes
      catalyzing the conjugation of amino acids onto cognate tRNAs. During eukaryotic
      evolution, tRNA synthetases have been the targets of persistent structural
      modifications. These modifications can be additive, as in the evolutionary
      acquisition of noncatalytic domains, or subtractive, as in the generation of
      truncated variants through regulated mechanisms such as proteolytic processing,
      alternative splicing, or coding region polyadenylation. A unique variant is the
      human glutamyl-prolyl-tRNA synthetase (EPRS) consisting of two fused synthetases
      joined by a linker containing three copies of the WHEP domain (termed by its
      presence in tryptophanyl-, histidyl-, and glutamyl-prolyl-tRNA synthetases).
      Here, we identify site-selective proteolysis as a mechanism that severs the
      linkage between the EPRS synthetases in vitro and in vivo Caspase action targeted
      Asp-929 in the third WHEP domain, thereby separating the two synthetases. Using a
      neoepitope antibody directed against the newly exposed C terminus, we demonstrate
      EPRS cleavage at Asp-929 in vitro and in vivo Biochemical and biophysical
      characterizations of the N-terminally generated EPRS proteoform containing the
      glutamyl-tRNA synthetase and most of the linker, including two WHEP domains,
      combined with structural analysis by small-angle neutron scattering, revealed a
      role for the WHEP domains in modulating conformations of the catalytic core and
      GSH-S-transferase-C-terminal-like (GST-C) domain. WHEP-driven conformational
      rearrangement altered GST-C domain interactions and conferred distinct oligomeric
      states in solution. Collectively, our results reveal long-range conformational
      changes imposed by the WHEP domains and illustrate how noncatalytic domains can
      modulate the global structure of tRNA synthetases in complex eukaryotic systems.

PMID- 29643182
TI  - My winding trail while fulfilling my love for science and family.
AB  - My winding path toward a career in science was awkward, like an adolescent
      finding an identity. It did not follow a classic course; it had many
      interruptions, complications, and challenges. It also involved a bit of luck and
      extremely supportive colleagues, mentors, and family, including my husband,
      children, and in-laws. I was inspired to tell my story here because I met a young
      woman interviewing in 2018 for graduate school who is growing up with the same
      complicated family expectations, social challenges, love for science, and desire
      to be a scientist as I had four decades ago. Her future is uncertain, because her
      chosen academic path is not encouraged by those around her. We, as a society,
      must find ways to encourage, promote, enable, and give strength to those who want
      to follow their dreams, despite facing many challenges in their lives. Here are
      some things I learned on my career path that I hope might be helpful for others.

PMID- 29643181
TI  - Smooth muscle cells differentiated from mesenchymal stem cells are regulated by
      microRNAs and suitable for vascular tissue grafts.
AB  - Tissue-engineered vascular grafts with long-term patency are greatly needed in
      the clinical settings, and smooth muscle cells (SMCs) are a critical graft
      component. Human mesenchymal stem cells (MSCs) are used for generating SMCs, and
      understanding the underlying regulatory mechanisms of the MSC-to-SMC
      differentiation process could improve SMC generation in the clinic. Here, we
      found that in response to stimulation of transforming growth factor-beta1
      (TGFbeta1), human umbilical cord-derived MSCs abundantly express the SMC markers
      alpha-smooth muscle actin (alphaSMA), smooth muscle protein 22 (SM22), calponin,
      and smooth muscle myosin heavy chain (SMMHC) at both gene and protein levels.
      Functionally, MSC-derived SMCs displayed contracting capacity in vitro and
      supported vascular structure formation in the Matrigel plug assay in vivo More
      importantly, SMCs differentiated from human MSCs could migrate into
      decellularized mouse aorta and give rise to the smooth muscle layer of vascular
      grafts, indicating the potential of utilizing human MSC-derived SMCs to generate
      vascular grafts. Of note, microRNA (miR) array analysis and TaqMan microRNA
      assays identified miR-503 and miR-222-5p as potential regulators of MSC
      differentiation into SMCs at early time points. Mechanistically, miR-503 promoted
      SMC differentiation by directly targeting SMAD7, a suppressor of SMAD-related,
      TGFbeta1-mediated signaling pathways. Moreover, miR-503 expression was SMAD4
      dependent. SMAD4 was enriched at the miR-503 promoter. Furthermore, miR-222-5p
      inhibited SMC differentiation by targeting and down-regulating ROCK2 and
      alphaSMA. In conclusion, MSC differentiation into SMCs is regulated by miR-503
      and miR-222-5p and yields functional SMCs for use in vascular grafts.

PMID- 29643171
TI  - Fungal Morphogenesis, from the Polarized Growth of Hyphae to Complex Reproduction
      and Infection Structures.
AB  - Filamentous fungi constitute a large group of eukaryotic microorganisms that grow
      by forming simple tube-like hyphae that are capable of differentiating into more
      complex morphological structures and distinct cell types. Hyphae form filamentous
      networks by extending at their tips while branching in subapical regions. Rapid
      tip elongation requires massive membrane insertion and extension of the rigid
      chitin-containing cell wall. This process is sustained by a continuous flow of
      secretory vesicles that depends on the coordinated action of the microtubule and
      actin cytoskeletons and the corresponding motors and associated proteins.
      Vesicles transport cell wall-synthesizing enzymes and accumulate in a special
      structure, the Spitzenkorper, before traveling further and fusing with the tip
      membrane. The place of vesicle fusion and growth direction are enabled and
      defined by the position of the Spitzenkorper, the so-called cell end markers, and
      other proteins involved in the exocytic process. Also important for tip extension
      is membrane recycling by endocytosis via early endosomes, which function as
      multipurpose transport vehicles for mRNA, septins, ribosomes, and peroxisomes.
      Cell integrity, hyphal branching, and morphogenesis are all processes that are
      largely dependent on vesicle and cytoskeleton dynamics. When hyphae differentiate
      structures for asexual or sexual reproduction or to mediate interspecies
      interactions, the hyphal basic cellular machinery may be reprogrammed through the
      synthesis of new proteins and/or the modification of protein activity. Although
      some transcriptional networks involved in such reprogramming of hyphae are well
      studied in several model filamentous fungi, clear connections between these
      networks and known determinants of hyphal morphogenesis are yet to be
      established.

PMID- 29643183
TI  - The HIRAN domain of helicase-like transcription factor positions the DNA
      translocase motor to drive efficient DNA fork regression.
AB  - Helicase-like transcription factor (HLTF) is a central mediator of the DNA damage
      response and maintains genome stability by regressing stalled replication forks.
      The N-terminal HIRAN domain binds specifically to the 3'-end of single-stranded
      DNA (ssDNA), and disrupting this function interferes with fork regression in
      vitro as well as replication fork progression in cells under replication stress.
      Here, we investigated the mechanism by which the HIRAN-ssDNA interaction
      facilitates fork remodeling. Our results indicated that HIRAN capture of a
      denatured nascent leading 3'-end directs specific binding of HLTF to forks. DNase
      footprinting revealed that HLTF binds to the parental duplex ahead of the fork
      and at the leading edge behind the fork. Moreover, we found that the HIRAN domain
      is important for initiating regression of forks when both nascent strands are at
      the junction, but is dispensable when forks contain ssDNA regions on either
      template strand. We also found that HLTF catalyzes fork restoration from a
      partially regressed structure in a HIRAN-dependent manner. Thus, HIRAN serves as
      a substrate-recognition domain to properly orient the ATPase motor domain at
      stalled and regressed forks and initiates fork remodeling by guiding formation of
      a four-way junction. We discuss how these activities compare with those of two
      related fork remodelers, SWI/SNF-related, matrix-associated, actin-dependent
      regulator of chromatin, subfamily A-like 1 (SMARCAL1) and zinc finger RANBP2 type
      containing 3 (ZRANB3) to provide insight into their nonredundant roles in DNA
      damage tolerance.

PMID- 29643184
TI  - Tracking the Cartoon mouse phenotype: Hemopexin domain-dependent regulation of
      MT1-MMP pericellular collagenolytic activity.
AB  - Following ENU mutagenesis, a phenodeviant line was generated, termed the "Cartoon
      mouse," that exhibits profound defects in growth and development. Cartoon mice
      harbor a single S466P point mutation in the MT1-MMP hemopexin domain, a 200-amino
      acid segment that is thought to play a critical role in regulating MT1-MMP
      collagenolytic activity. Herein, we demonstrate that the MT1-MMPS466P mutation
      replicates the phenotypic status of Mt1-mmp-null animals as well as the
      functional characteristics of MT1-MMP-/- cells. However, rather than a loss-of
      function mutation acquired as a consequence of defects in MT1-MMP proteolytic
      activity, the S466P substitution generates a misfolded, temperature-sensitive
      mutant that is abnormally retained in the endoplasmic reticulum (ER). By
      contrast, the WT hemopexin domain does not play a required role in regulating MT1
      MMP trafficking, as a hemopexin domain-deletion mutant is successfully mobilized
      to the cell surface and displays nearly normal collagenolytic activity.
      Alternatively, when MT1-MMPS466P-expressing cells are cultured at a permissive
      temperature of 25  degrees C that depresses misfolding, the mutant successfully
      traffics from the ER to the trans-Golgi network (ER -> trans-Golgi network),
      where it undergoes processing to its mature form, mobilizes to the cell surface,
      and expresses type I collagenolytic activity. Together, these analyses define the
      Cartoon mouse as an unexpected gain-of-abnormal function mutation, wherein the
      temperature-sensitive mutant phenocopies MT1-MMP-/- mice as a consequence of
      eliciting a specific ER -> trans-Golgi network trafficking defect.

PMID- 29643187
TI  - Alpha-Band Oscillation Mediates the Temporal Organization of Serially Presented
      Flashes.

PMID- 29643185
TI  - Expression of mutant Asxl1 perturbs hematopoiesis and promotes susceptibility to
      leukemic transformation.
AB  - Additional sex combs like 1 (ASXL1) is frequently mutated in myeloid malignancies
      and clonal hematopoiesis of indeterminate potential (CHIP). Although loss of
      ASXL1 promotes hematopoietic transformation, there is growing evidence that ASXL1
      mutations might confer an alteration of function. In this study, we identify that
      physiological expression of a C-terminal truncated Asxl1 mutant in vivo using
      conditional knock-in (KI) results in myeloid skewing, age-dependent anemia,
      thrombocytosis, and morphological dysplasia. Although expression of mutant Asxl1
      altered the functions of hematopoietic stem cells (HSCs), it maintained their
      survival in competitive transplantation assays and increased susceptibility to
      leukemic transformation by co-occurring RUNX1 mutation or viral insertional
      mutagenesis. KI mice displayed substantial reductions in H3K4me3 and H2AK119Ub
      without significant reductions in H3K27me3, distinct from the effects of Asxl1
      loss. Chromatin immunoprecipitation followed by next-generation sequencing
      analysis demonstrated opposing effects of wild-type and mutant Asxl1 on H3K4me3.
      These findings reveal that ASXL1 mutations confer HSCs with an altered epigenome
      and increase susceptibility for leukemic transformation, presenting a novel model
      for CHIP.

PMID- 29643188
TI  - Onset Matters: How Collicular Activity Relates to Saccade Initiation during
      Cortical Cooling.

PMID- 29643186
TI  - Peripherally derived macrophages can engraft the brain independent of irradiation
      and maintain an identity distinct from microglia.
AB  - Peripherally derived macrophages infiltrate the brain after bone marrow
      transplantation and during central nervous system (CNS) inflammation. It was
      initially suggested that these engrafting cells were newly derived microglia and
      that irradiation was essential for engraftment to occur. However, it remains
      unclear whether brain-engrafting macrophages (beMphis) acquire a unique phenotype
      in the brain, whether long-term engraftment may occur without irradiation, and
      whether brain function is affected by the engrafted cells. In this study, we
      demonstrate that chronic, partial microglia depletion is sufficient for beMphis
      to populate the niche and that the presence of beMphis does not alter behavior.
      Furthermore, beMphis maintain a unique functional and transcriptional identity as
      compared with microglia. Overall, this study establishes beMphis as a unique CNS
      cell type and demonstrates that therapeutic engraftment of beMphis may be
      possible with irradiation-free conditioning regimens.

PMID- 29643189
TI  - Elevated Hepatic CD1d Levels Coincide with Invariant NKT Cell Defects in Chronic
      Hepatitis B Virus Infection.
AB  - Activation of invariant NKT (iNKT) cells manifests antiviral immune responses in
      vivo. However, clinical trials have failed to show consistent hepatitis B virus
      (HBV) DNA reduction postadministration of iNKT cell-specific agonist alpha
      galactosylceramide (alpha-GalCer). In this study, we aimed to investigate HBV
      infection-related iNKT cell defects and explore iNKT cell-based therapeutic
      potential for chronic hepatitis B (CHB). Liver specimens from 30 HBV-infected
      hepatocellular carcinoma patients were collected for CD1d/hepatitis B surface Ag
      (HBsAg) staining and/or intrahepatic iNKT cell assay. Two hundred and six chronic
      HBV-infected patients (including 130 CHB patients) were enrolled in the study of
      circulating iNKT cell frequency and function. We found that liver and hepatoma
      tissue that positively stained for HBsAg had higher CD1d expression as compared
      with HBsAg negatively stained counterparts. The elevated CD1d expression in
      infected tissue is supposed to facilitate the iNKT cell-based antiviral effects
      locally. However, iNKT cell defects that related with disease progression
      suggested iNKT cells attenuated their effects during chronic HBV infection. The
      residual iNKT cells in CHB patients showed aberrant activation and
      hyporesponsiveness to alpha-GalCer. Exogenous IL-2 fully rescued alpha-GalCer
      induced expansion of iNKT cells from CHB patients, and synergistic effects of IL
      2 and IL-15 helped to recover the CD1d-dependent IFN-gamma production. In
      conclusion, our results highlight the increased CD1d expression in HBV-infected
      liver and differential iNKT cell defects associated with disease progression
      during chronic HBV infection. The reversibility of iNKT cell defects suggests
      protective immune responses could be partially recovered in CHB.

PMID- 29643191
TI  - CD83 Antibody Inhibits Human B Cell Responses to Antigen as well as Dendritic
      Cell-Mediated CD4 T Cell Responses.
AB  - Anti-CD83 Ab capable of Ab-dependent cellular cytotoxicity can deplete activated
      CD83+ human dendritic cells, thereby inhibiting CD4 T cell-mediated acute graft
      versus-host disease. As CD83 is also expressed on the surface of activated B
      lymphocytes, we hypothesized that anti-CD83 would also inhibit B cell responses
      to stimulation. We found that anti-CD83 inhibited total IgM and IgG production in
      vitro by allostimulated human PBMC. Also, Ag-specific Ab responses to
      immunization of SCID mice xenografted with human PBMC were inhibited by anti-CD83
      treatment. This inhibition occurred without depletion of all human B cells
      because anti-CD83 lysed activated CD83+ B cells by Ab-dependent cellular
      cytotoxicity and spared resting (CD83-) B cells. In cultured human PBMC, anti
      CD83 inhibited tetanus toxoid-stimulated B cell proliferation and concomitant
      dendritic cell-mediated CD4 T cell proliferation and expression of IFN-gamma and
      IL-17A, with minimal losses of B cells (<20%). In contrast, the anti-CD20 mAb
      rituximab depleted >80% of B cells but had no effect on CD4 T cell proliferation
      and cytokine expression. By virtue of the ability of anti-CD83 to selectively
      deplete activated, but not resting, B cells and dendritic cells, with the latter
      reducing CD4 T cell responses, anti-CD83 may be clinically useful in autoimmunity
      and transplantation. Advantages might include inhibited expansion of autoantigen-
      or alloantigen-specific B cells and CD4 T cells, thus preventing further
      production of pathogenic Abs and inflammatory cytokines while preserving
      protective memory and regulatory cells.

PMID- 29643190
TI  - Peptide Vaccine Formulation Controls the Duration of Antigen Presentation and
      Magnitude of Tumor-Specific CD8+ T Cell Response.
AB  - Despite remarkable progresses in vaccinology, therapeutic cancer vaccines have
      not achieved their full potential. We previously showed that an excessively long
      duration of Ag presentation critically reduced the quantity and quality of
      vaccination-induced T cell responses and subsequent antitumor efficacy. In this
      study, using a murine model and tumor cell lines, we studied l-tyrosine amino
      acid-based microparticles as a peptide vaccine adjuvant with a short-term Ag
      depot function for the induction of tumor-specific T cells. l-Tyrosine
      microparticles did not induce dendritic cell maturation, and their adjuvant
      activity was not mediated by inflammasome activation. Instead, prolonged Ag
      presentation in vivo translated into increased numbers and antitumor activity of
      vaccination-induced CD8+ T cells. Indeed, prolonging Ag presentation by repeated
      injection of peptide in saline resulted in an increase in T cell numbers similar
      to that observed after vaccination with peptide/l-tyrosine microparticles. Our
      results show that the duration of Ag presentation is critical for optimal
      induction of antitumor T cells, and can be manipulated through vaccine
      formulation.

PMID- 29643192
TI  - Characterizing the Mechanisms of Nonopsonic Uptake of Cryptococci by Macrophages.
AB  - The pathogenic fungus Cryptococcus enters the human host via inhalation into the
      lung and is able to reside in a niche environment that is serum- (opsonin)
      limiting. Little is known about the mechanism by which nonopsonic phagocytosis
      occurs via phagocytes in such situations. Using a combination of soluble
      inhibitors of phagocytic receptors and macrophages derived from knockout mice and
      human volunteers, we show that uptake of nonopsonized Cryptococcus neoformans and
      C. gattii via the mannose receptor is dependent on macrophage activation by
      cytokines. However, although uptake of C. neoformans is via both dectin-1 and
      dectin-2, C. gattii uptake occurs largely via dectin-1. Interestingly, dectin
      inhibitors also blocked phagocytosis of unopsonized Cryptococci in wax moth
      (Galleria mellonella) larvae and partially protected the larvae from infection by
      both fungi, supporting a key role for host phagocytes in augmenting early disease
      establishment. Finally, we demonstrated that internalization of nonopsonized
      Cryptococci is not accompanied by the nuclear translocation of NF-kappaB or its
      concomitant production of proinflammatory cytokines such as TNF-alpha. Thus,
      nonopsonized Cryptococci are recognized by mammalian phagocytes in a manner that
      minimizes proinflammatory cytokine production and potentially facilitates fungal
      pathogenesis.

PMID- 29643193
TI  - Cutting Edge: Protection by Antiviral Memory CD8 T Cells Requires Rapidly
      Produced Antigen in Large Amounts.
AB  - Numerous attempts to produce antiviral vaccines by harnessing memory CD8 T cells
      have failed. A barrier to progress is that we do not know what makes an Ag a
      viable target of protective CD8 T cell memory. We found that in mice susceptible
      to lethal mousepox (the mouse homolog of human smallpox), a dendritic cell
      vaccine that induced memory CD8 T cells fully protected mice when the infecting
      virus produced Ag in large quantities and with rapid kinetics. Protection did not
      occur when the Ag was produced in low amounts, even with rapid kinetics, and
      protection was only partial when the Ag was produced in large quantities but with
      slow kinetics. Hence, the amount and timing of Ag expression appear to be key
      determinants of memory CD8 T cell antiviral protective immunity. These findings
      may have important implications for vaccine design.

PMID- 29643194
TI  - Quantitative Thresholds Enable Accurate Identification of Clostridium difficile
      Infection by the Luminex xTAG Gastrointestinal Pathogen Panel.
AB  - Clostridium difficile colonizes the gastrointestinal (GI) tract, resulting in
      either asymptomatic carriage or a spectrum of diarrheal illness. If clinical
      suspicion for C. difficile is low, stool samples are often submitted for analysis
      by multiplex molecular assays capable of detecting multiple GI pathogens, and
      some institutions do not report this organism due to concerns for high false
      positive rates. Since clinical disease correlates with organism burden and
      molecular assays yield quantitative data, we hypothesized that numerical cutoffs
      could be utilized to improve the specificity of the Luminex xTAG GI pathogen
      panel (GPP) for C. difficile infection. Analysis of cotested liquid stool samples
      (n = 1,105) identified a GPP median fluorescence intensity (MFI) value cutoff of
      >=1,200 to be predictive of two-step algorithm (2-SA; 96.4% concordance) and
      toxin enzyme immunoassay (EIA) positivity. Application of this cutoff to a second
      cotested data set (n = 1,428) yielded 96.5% concordance. To determine test
      performance characteristics, concordant results were deemed positive or negative,
      and discordant results were adjudicated via chart review. Test performance
      characteristics for the MFI cutoff of >=150 (standard), MFI cutoff of >=1,200,
      and 2-SA were as follows (respectively): concordance, 95, 96, and 97%;
      sensitivity, 93, 78, and 90%; specificity, 95, 98, and 98%; positive predictive
      value, 67, 82, and 81%;, and negative predictive value, 99, 98, and 99%. To
      capture the high sensitivity for organism detection (MFI of >=150) and high
      specificity for active infection (MFI of >=1,200), we developed and applied a
      reporting algorithm to interpret GPP data from patients (n = 563) with clinician
      orders only for syndromic panel testing, thus enabling accurate reporting of C.
      difficile for 95% of samples (514 negative and 5 true positives) irrespective of
      initial clinical suspicion and without the need for additional testing.

PMID- 29643195
TI  - Diagnostic Performance of a Molecular Test versus Clinician Assessment of
      Vaginitis.
AB  - Vaginitis is a common complaint, diagnosed either empirically or using Amsel's
      criteria and wet mount microscopy. This study sought to determine characteristics
      of an investigational test (a molecular test for vaginitis), compared to
      reference, for detection of bacterial vaginosis, Candida spp., and Trichomonas
      vaginalis Vaginal specimens from a cross-sectional study were obtained from 1,740
      women (>=18 years old), with vaginitis symptoms, during routine clinic visits
      (across 10 sites in the United States). Specimens were analyzed using a
      commercial PCR/fluorogenic probe-based investigational test that detects
      bacterial vaginosis, Candida spp., and Trichomonas vaginalis Clinician diagnosis
      and in-clinic testing (Amsel's test, potassium hydroxide preparation, and wet
      mount) were also employed to detect the three vaginitis causes. All testing
      methods were compared to the respective reference methods (Nugent Gram stain for
      bacterial vaginosis, detection of the Candida gene its2, and Trichomonas
      vaginalis culture). The investigational test, clinician diagnosis, and in-clinic
      testing were compared to reference methods for bacterial vaginosis, Candida spp.,
      and Trichomonas vaginalis The investigational test resulted in significantly
      higher sensitivity and negative predictive value than clinician diagnosis or in
      clinic testing. In addition, the investigational test showed a statistically
      higher overall percent agreement with each of the three reference methods than
      did clinician diagnosis or in-clinic testing. The investigational test showed
      significantly higher sensitivity for detecting vaginitis, involving more than one
      cause, than did clinician diagnosis. Taken together, these results suggest that a
      molecular investigational test can facilitate accurate detection of vaginitis.

PMID- 29643196
TI  - Winners of the American Society for Microbiology Awards in Clinical Microbiology.

PMID- 29643197
TI  - Whole-Genome Sequencing of Recent Listeria monocytogenes Isolates from Germany
      Reveals Population Structure and Disease Clusters.
AB  - Listeria monocytogenes causes foodborne outbreaks with high mortality. For
      improvement of outbreak cluster detection, the German consiliary laboratory for
      listeriosis implemented whole-genome sequencing (WGS) in 2015. A total of 424
      human L. monocytogenes isolates collected in 2007 to 2017 were subjected to WGS
      and core-genome multilocus sequence typing (cgMLST). cgMLST grouped the isolates
      into 38 complexes, reflecting 4 known and 34 unknown disease clusters. Most of
      these complexes were confirmed by single nucleotide polymorphism (SNP) calling,
      but some were further differentiated. Interestingly, several cgMLST cluster types
      were further subtyped by pulsed-field gel electrophoresis, partly due to phage
      insertions in the accessory genome. Our results highlight the usefulness of
      cgMLST for routine cluster detection but also show that cgMLST complexes require
      validation by methods providing higher typing resolution. Twelve cgMLST clusters
      included recent cases, suggesting activity of the source. Therefore, the cgMLST
      nomenclature data presented here may support future public health actions.

PMID- 29643198
TI  - Development of a Real-Time Reverse Transcription-PCR Assay for Global
      Differentiation of Yellow Fever Virus Vaccine-Related Adverse Events from Natural
      Infections.
AB  - Yellow fever (YF) is a reemerging public health threat, with frequent outbreaks
      prompting large vaccination campaigns in regions of endemicity in Africa and
      South America. Specific detection of vaccine-related adverse events is resource
      intensive, time-consuming, and difficult to achieve during an outbreak. To
      address this, we have developed a highly transferable rapid yellow fever virus
      (YFV) vaccine-specific real-time reverse transcription-PCR (RT-PCR) assay that
      distinguishes vaccine from wild-type lineages. The assay utilizes a specific
      hydrolysis probe that includes locked nucleic acids to enhance specific
      discrimination of the YFV17D vaccine strain genome. Promisingly, sensitivity and
      specificity analyses reveal this assay to be highly specific to vaccine strain(s)
      when tested on clinical samples and YFV cell culture isolates of global origin.
      Taken together, our data suggest the utility of this assay for use in
      laboratories of varied capacity for the identification and differentiation of
      vaccine-related adverse events from wild-type infections of both African and
      South American origin.

PMID- 29643199
TI  - Usefulness of Kaposi's Sarcoma-Associated Herpesvirus (KSHV) DNA Viral Load in
      Whole Blood for Diagnosis and Monitoring of KSHV-Associated Diseases.

PMID- 29643200
TI  - Use of Automated Urine Microscopy Analysis in Clinical Diagnosis of Urinary Tract
      Infection: Defining an Optimal Diagnostic Score in an Academic Medical Center
      Population.
AB  - A retrospective case record study was conducted that established a scoring tool
      based on clinical and iQ200 parameters, able to predict or rule out the clinical
      diagnosis of UTI in the majority of adult patients in an academic hospital.
      Automated standardized quantitative urine analysis, such as iQ200 analysis, is on
      the rise because of its high accuracy and efficiency compared to those of
      traditional urine analysis. Previous research on automated urinalysis focused
      mainly on predicting culture results but not on the clinical diagnosis of urinary
      tract infection (UTI). A retrospective analysis was conducted of consecutive
      urine samples sent in for culture because of suspected UTI. UTI was defined by
      expert opinion, based on reported symptoms, conventional urine sediment analysis,
      and urine cultures. Parameters of iQ200 analysis and clinical symptoms and signs
      were compared between cases and controls. Optimal cutoff values were determined
      for iQ200 parameters, and multivariate logistic regression analysis was used to
      identify the set of variables that best predicts the clinical diagnosis of UTI
      for development of a scoring tool. A total of 382 patients were included. Optimal
      cutoff values of iQ200 analysis were 74 white blood cells (WBC)/MUl, 6,250 "all
      small particles" (ASP)/MUl, and a bacterial score of 2 on an ordinal scale of 0
      to 5. The scoring tool attributed 1 point for frequent micturition or increased
      urge, 2 points for dysuria, 1 point for a bacterial score of >=2, 2 points for
      WBC/MUl of >=50, and an additional point for WBC/MUl of >=150. This score had a
      sensitivity of 86% and a specificity of 92% when using a threshold of <4 points.
      The combination of iQ200 analysis and a simple survey could predict or rule out
      UTIs in a majority of patients in an academic medical center.

PMID- 29643201
TI  - Nipah Virus Infection.
AB  - Nipah virus, a paramyxovirus related to Hendra virus, first emerged in Malaysia
      in 1998. Clinical presentation ranges from asymptomatic infection to fatal
      encephalitis. Malaysia has had no more cases since 1999, but outbreaks continue
      to occur in Bangladesh and India. In the Malaysia-Singapore outbreak,
      transmission occurred primarily through contact with pigs, whereas in Bangladesh
      and India, it is associated with ingestion of contaminated date palm sap and
      human-to-human transmission. Bats are the main reservoir for this virus, which
      can cause disease in humans and animals. There are currently no effective
      therapeutics, and supportive care and prevention are the mainstays of management.

PMID- 29643202
TI  - Comparison of Diagnostic Accuracy of Periprosthetic Tissue Culture in Blood
      Culture Bottles to That of Prosthesis Sonication Fluid Culture for Diagnosis of
      Prosthetic Joint Infection (PJI) by Use of Bayesian Latent Class Modeling and
      IDSA PJI Criteria for Classification.
AB  - We have previously demonstrated that culturing periprosthetic tissue in blood
      culture bottles (BCBs) improves sensitivity compared to conventional agar and
      broth culture methods for diagnosis of prosthetic joint infection (PJI). We have
      also shown that prosthesis sonication culture improves sensitivity compared to
      periprosthetic tissue culture using conventional agar and broth methods. The
      purpose of this study was to compare the diagnostic accuracy of tissue culture in
      BCBs (subsequently referred to as tissue culture) to prosthesis sonication
      culture (subsequently referred to as sonicate fluid culture). We studied 229
      subjects who underwent arthroplasty revision or resection surgery between March
      2016 and October 2017 at Mayo Clinic in Rochester, Minnesota. Using the
      Infectious Diseases Society of America (IDSA) PJI diagnostic criteria (omitting
      culture criteria) as the gold standard, the sensitivity of tissue culture was
      similar to that of the sonicate fluid culture (66.4% versus 73.1%, P = 0.07) but
      was significantly lower than that of the two tests combined (66.4% versus 76.9%,
      P < 0.001). Using Bayesian latent class modeling, which assumes no gold standard
      for PJI diagnosis, the sensitivity of tissue culture was slightly lower than that
      of sonicate fluid culture (86.3% versus 88.7%) and much lower than that of the
      two tests combined (86.3% versus 99.1%). In conclusion, tissue culture in BCBs
      reached sensitivity similar to that of prosthesis sonicate fluid culture for
      diagnosis of PJI, but the two tests combined had the highest sensitivity without
      compromising specificity. The combination of tissue culture in BCBs and sonicate
      fluid culture is recommended to achieve the highest level of microbiological
      diagnosis of PJI.

PMID- 29643203
TI  - Evaluation of the Vitek MS v3.0 Matrix-Assisted Laser Desorption Ionization-Time
      of Flight Mass Spectrometry System for Identification of Mycobacterium and
      Nocardia Species.
AB  - This multicenter study was designed to assess the accuracy and reproducibility of
      the Vitek MS v3.0 matrix-assisted laser desorption ionization-time of flight
      (MALDI-TOF) mass spectrometry system for identification of Mycobacterium and
      Nocardia species compared to DNA sequencing. A total of 963 clinical isolates
      representing 51 taxa were evaluated. In all, 663 isolates were correctly
      identified to the species level (69%), with another 231 (24%) correctly
      identified to the complex or group level. Fifty-five isolates (6%) could not be
      identified despite repeat testing. All of the tuberculous mycobacteria (45/45;
      100%) and most of the nontuberculous mycobacteria (569/606; 94%) were correctly
      identified at least to the group or complex level. However, not all species or
      subspecies within the M. tuberculosis, M. abscessus, and M. avium complexes and
      within the M. fortuitum and M. mucogenicum groups could be differentiated. Among
      the 312 Nocardia isolates tested, 236 (76%) were correctly identified to the
      species level, with an additional 44 (14%) correctly identified to the complex
      level. Species within the N. nova and N. transvalensis complexes could not always
      be differentiated. Eleven percent of the isolates (103/963) underwent repeat
      testing in order to get a final result. Identification of a representative set of
      Mycobacterium and Nocardia species was highly reproducible, with 297 of 300 (99%)
      replicates correctly identified using multiple kit lots, instruments, analysts,
      and sites. These findings demonstrate that the system is robust and has utility
      for the routine identification of mycobacteria and Nocardia in clinical practice.

PMID- 29643206
TI  - Land uplift creates important meadow habitat and a potential original niche for
      grassland species.
AB  - Semi-natural grasslands have been severely affected by agricultural land-use
      change. However, the isostatic land adjustment following deglaciation in the
      Northern Hemisphere means that new land is continually being created in coastal
      areas. We modelled isostatic adjustment during the last 4000 years in a region of
      the Baltic coast to estimate the emergence of potential grassland habitat. We
      also compared the alpha and beta diversity of existing managed and abandoned
      coastal meadows, and assessed their contribution to biodiversity at landscape
      scales. We estimated that half the 7866 km2 of emerging land had the potential to
      become coastal meadow habitat, which is an order of magnitude larger than the
      total area of all valuable semi-natural grassland in the study region today. The
      small area of managed coastal habitat remaining was found to have a
      disproportionate influence on the richness of threatened species at landscape
      scales, but our results also show that continued management is essential for the
      maintenance of grassland biodiversity. Our combination of approaches identifies
      uplifted coastal meadows as an additional original niche for grassland plant
      species, while highlighting that low-intensity disturbance through grassland
      management is essential for the maintenance of diversity at multiple scales.

PMID- 29643205
TI  - In vitro iCLIP-based modeling uncovers how the splicing factor U2AF2 relies on
      regulation by cofactors.
AB  - Alternative splicing generates distinct mRNA isoforms and is crucial for proteome
      diversity in eukaryotes. The RNA-binding protein (RBP) U2AF2 is central to
      splicing decisions, as it recognizes 3' splice sites and recruits the
      spliceosome. We establish "in vitro iCLIP" experiments, in which recombinant RBPs
      are incubated with long transcripts, to study how U2AF2 recognizes RNA sequences
      and how this is modulated by trans-acting RBPs. We measure U2AF2 affinities at
      hundreds of binding sites and compare in vitro and in vivo binding landscapes by
      mathematical modeling. We find that trans-acting RBPs extensively regulate U2AF2
      binding in vivo, including enhanced recruitment to 3' splice sites and clearance
      of introns. Using machine learning, we identify and experimentally validate novel
      trans-acting RBPs (including FUBP1, CELF6, and PCBP1) that modulate U2AF2 binding
      and affect splicing outcomes. Our study offers a blueprint for the high
      throughput characterization of in vitro mRNP assembly and in vivo splicing
      regulation.

PMID- 29643204
TI  - L1 retrotransposition is a common feature of mammalian hepatocarcinogenesis.
AB  - The retrotransposon Long Interspersed Element 1 (LINE-1 or L1) is a continuing
      source of germline and somatic mutagenesis in mammals. Deregulated L1 activity is
      a hallmark of cancer, and L1 mutagenesis has been described in numerous human
      malignancies. We previously employed retrotransposon capture sequencing (RC-seq)
      to analyze hepatocellular carcinoma (HCC) samples from patients infected with
      hepatitis B or hepatitis C virus and identified L1 variants responsible for
      activating oncogenic pathways. Here, we have applied RC-seq and whole-genome
      sequencing (WGS) to an Abcb4 (Mdr2)-/- mouse model of hepatic carcinogenesis and
      demonstrated for the first time that L1 mobilization occurs in murine tumors. In
      12 HCC nodules obtained from 10 animals, we validated four somatic L1 insertions
      by PCR and capillary sequencing, including TF subfamily elements, and one GF
      subfamily example. One of the TF insertions carried a 3' transduction, allowing
      us to identify its donor L1 and to demonstrate that this full-length TF element
      retained retrotransposition capacity in cultured cancer cells. Using RC-seq, we
      also identified eight tumor-specific L1 insertions from 25 HCC patients with a
      history of alcohol abuse. Finally, we used RC-seq and WGS to identify three tumor
      specific L1 insertions among 10 intra-hepatic cholangiocarcinoma (ICC) patients,
      including one insertion traced to a donor L1 on Chromosome 22 known to be highly
      active in other cancers. This study reveals L1 mobilization as a common feature
      of hepatocarcinogenesis in mammals, demonstrating that the phenomenon is not
      restricted to human viral HCC etiologies and is encountered in murine liver
      tumors.

PMID- 29643207
TI  - Synchronous diversification of Sulawesi's iconic artiodactyls driven by recent
      geological events.
AB  - The high degree of endemism on Sulawesi has previously been suggested to have
      vicariant origins, dating back to 40 Ma. Recent studies, however, suggest that
      much of Sulawesi's fauna assembled over the last 15 Myr. Here, we test the
      hypothesis that more recent uplift of previously submerged portions of land on
      Sulawesi promoted diversification and that much of its faunal assemblage is much
      younger than the island itself. To do so, we combined palaeogeographical
      reconstructions with genetic and morphometric datasets derived from Sulawesi's
      three largest mammals: the babirusa, anoa and Sulawesi warty pig. Our results
      indicate that although these species most likely colonized the area that is now
      Sulawesi at different times (14 Ma to 2-3 Ma), they experienced an almost
      synchronous expansion from the central part of the island. Geological
      reconstructions indicate that this area was above sea level for most of the last
      4 Myr, unlike most parts of the island. We conclude that emergence of land on
      Sulawesi (approx. 1-2 Myr) may have allowed species to expand synchronously.
      Altogether, our results indicate that the establishment of the highly endemic
      faunal assemblage on Sulawesi was driven by geological events over the last few
      million years.

PMID- 29643208
TI  - Network integration and limits to social inheritance in vervet monkeys.
AB  - Social networks can be adaptive for members and a recent model (Ilany and Akcay
      2016 Nat. Comm.7, 12084 (doi:10.1038/ncomms12084)) has demonstrated that network
      structure can be maintained by a simple process of social inheritance. Here, we
      ask how juvenile vervet monkeys integrate into their adult grooming networks,
      using the model to test whether observed grooming patterns replicate network
      structure. Female juveniles, who are philopatric, increased their grooming effort
      towards adults more than males, although this was not reciprocated by the adults
      themselves. While more consistent maternal grooming networks, together with
      maternal network strength, predicted increasing similarity in the patterning of
      mother-daughter grooming allocations, daughters' grooming networks generally did
      not match closely those of their mothers. However, maternal networks themselves
      were not very consistent across time, thus presenting youngsters with a moving
      target that may be difficult to match. Observed patterns of juvenile female
      grooming did not replicate the adult network, for which increased association
      with adults not groomed by their mothers would be necessary. These results
      suggest that network flexibility, not stability, characterizes our groups and
      that juveniles are exposed to, and must learn to cope with, temporal shifts in
      network structure. We hypothesize that this may lead to individual variation in
      behavioural flexibility, which in turn may help explain why and how variation in
      sociability influences fitness.

PMID- 29643209
TI  - Impacts of ocean acidification on sea urchin growth across the juvenile to mature
      adult life-stage transition is mitigated by warming.
AB  - Understanding how growth trajectories of calcifying invertebrates are affected by
      changing climate requires acclimation experiments that follow development across
      life-history transitions. In a long-term acclimation study, the effects of
      increased acidification and temperature on survival and growth of the tropical
      sea urchin Tripneustes gratilla from the early juvenile (5 mm test diameter-TD)
      through the developmental transition to the mature adult (60 mm TD) were
      investigated. Juveniles were reared in a combination of three temperature and
      three pH/pCO2 treatments, including treatments commensurate with global change
      projections. Elevated temperature and pCO2/pH both affected growth, but there was
      no interaction between these factors. The urchins grew more slowly at pH 7.6, but
      not at pH 7.8. Slow growth may be influenced by the inability to compensate
      coelomic fluid acid-base balance at pH 7.6. Growth was faster at +3 and +6
      degrees C compared to that in ambient temperature. Acidification and warming had
      strong and interactive effects on reproductive potential. Warming increased the
      gonad index, but acidification decreased it. At pH 7.6 there were virtually no
      gonads in any urchins regardless of temperature. The T. gratilla were larger at
      maturity under combined near-future warming and acidification scenarios (+3
      degrees C/pH 7.8). Although the juveniles grew and survived in near-future
      warming and acidification conditions, chronic exposure to these stressors from an
      early stage altered allocation to somatic and gonad growth. In the absence of
      phenotypic adjustment, the interactive effects of warming and acidification on
      the benthic life phases of sea urchins may compromise reproductive fitness and
      population maintenance as global climatic change unfolds.

PMID- 29643210
TI  - Heritable spouse effects increase evolutionary potential of human reproductive
      timing.
AB  - Sexual reproduction is inherently interactive, especially in animal species such
      as humans that exhibit extended pair bonding. Yet we have little knowledge of the
      role of male characteristics and their evolutionary impact on reproductive
      behavioural phenotypes, to the extent that biologists typically consider
      component traits (e.g. reproductive timing) as female-specific. Based on
      extensive genealogical data detailing the life histories of 6435 human mothers
      born across four centuries of modern history, we use an animal modelling approach
      to estimate the indirect genetic effect of men on the reproductive phenotype of
      their partners. These analyses show that a woman's reproductive timing (age at
      first birth) is influenced by her partner's genotype. This indirect genetic
      effect is positively correlated with the direct genetic effect expressed in
      women, such that total heritable variance in this trait is doubled when heritable
      partner effects are considered. Our study thus suggests that much of the
      heritable variation in women's reproductive timing is mediated via partner
      effects, and that the evolutionary potential of this trait is far greater than
      previously appreciated.

PMID- 29643211
TI  - Microbial decay analysis challenges interpretation of putative organ systems in
      Cambrian fuxianhuiids.
AB  - The Chengjiang fossil Lagerstatte (Cambrian Stage 3) from Yunnan, southern China
      is renowned for its soft-tissue preservation. Accordingly structures in
      fuxianhuiids, radiodontans and great appendage arthropods have been interpreted
      as the nervous and cardiovascular systems, including brains, hearts and blood
      vessels. That such delicate organ systems survive the fossilization process seems
      remarkable; given that this mode of preservation involves major taphonomic
      changes, such as flattening, microbial degradation, chemical alteration and
      replacement. Here, we document a range of taphonomic preservation states in
      numerous articulated individuals of Fuxianhuia protensa We suggest that organic
      (partly iron mineral-replaced) bulbous structures in the head region, previously
      interpreted as brain tissue, along with sagittally located organic strands
      interpreted as part of the cardiovascular system or as nerve cords, may be better
      explained as microbial biofilms that developed following decomposition of the
      intestine, muscle and other connective tissues, forming halos surrounding the
      original organic remains.

PMID- 29643212
TI  - Stable social relationships between unrelated females increase individual fitness
      in a cooperative bird.
AB  - Social animals often form long-lasting relationships with fellow group members,
      usually with close kin. In primates, strong social bonds have been associated
      with increased longevity, offspring survival and reproductive success. However,
      little is known about the fitness effects of social bonds between non-kin,
      especially outside of mammals. In this study, we use long-term field research on
      a cooperatively breeding bird, the greater ani (Crotophaga major), to ask whether
      adult females benefit by remaining in long-term associations with unrelated, co
      breeding females. We find that females that have previously nested together
      synchronize their reproduction more rapidly than those nesting with unfamiliar
      partners, which leads to lower competition and higher fledging success.
      Importantly, although previous experience with a co-breeding female influenced
      reproductive synchrony, the degree of reproductive synchrony did not influence
      whether co-breeding females remained together in subsequent years, ruling out the
      alternate hypothesis that highly synchronized females are simply more likely to
      remain together. These results indicate that switching groups is costly to
      females, and that social familiarity improves reproductive coordination. Stable
      social relationships therefore have significant fitness consequences for
      cooperatively nesting female birds, suggesting that direct benefits alone may
      favour the evolution of associations between non-relatives and contribute to long
      term group stability.

PMID- 29643213
TI  - Calcium isotopes offer clues on resource partitioning among Cretaceous predatory
      dinosaurs.
AB  - Large predators are overabundant in mid-Cretaceous continental dinosaur
      assemblages of North Africa. Such unbalanced ecosystem structure involves, among
      predatory dinosaurs, typical abelisaurid or carcharodontosaurid theropods co
      occurring with long-snouted spinosaurids of debated ecology. Here, we report
      calcium (Ca) isotope values from tooth enamel (expressed as delta44/42Ca) to
      investigate resource partitioning in mid-Cretaceous assemblages from Niger
      (Gadoufaoua) and Morocco (Kem Kem Beds). In both assemblages, spinosaurids
      display a distinct isotopic signature, the most negative in our dataset. This
      distinct taxonomic clustering in Ca isotope values observed between spinosaurids
      and other predators provides unambiguous evidence for niche partitioning at the
      top of the trophic chains: spinosaurids foraged on aquatic environments while
      abelisaurid and carcharodontosaurid theropods relied almost exclusively on
      terrestrial resources.

PMID- 29643214
TI  - Anemone bleaching increases the metabolic demands of symbiont anemonefish.
AB  - Increased ocean temperatures are causing mass bleaching of anemones and corals in
      the tropics worldwide. While such heat-induced loss of algal symbionts
      (zooxanthellae) directly affects anemones and corals physiologically, this damage
      may also cascade on to other animal symbionts. Metabolic rate is an integrative
      physiological trait shown to relate to various aspects of organismal performance,
      behaviour and locomotor capacity, and also shows plasticity during exposure to
      acute and chronic stressors. As climate warming is expected to affect the
      physiology, behaviour and life history of animals, including ectotherms such as
      fish, we measured if residing in bleached versus unbleached sea anemones
      (Heteractis magnifica) affected the standard (i.e. baseline) metabolic rate and
      behaviour (activity) of juvenile orange-fin anemonefish (Amphiprion
      chrysopterus). Metabolic rate was estimated from rates of oxygen uptake [Formula:
      see text], and the standard metabolic rate [Formula: see text] of anemonefish
      from bleached anemones was significantly higher by 8.2% compared with that of
      fish residing in unbleached anemones, possibly due to increased stress levels.
      Activity levels did not differ between fish from bleached and unbleached
      anemones. As [Formula: see text] reflects the minimum cost of living, the
      increased metabolic demands may contribute to the negative impacts of bleaching
      on important anemonefish life history and fitness traits observed previously
      (e.g. reduced spawning frequency and lower fecundity).

PMID- 29643215
TI  - Do priority effects outweigh environmental filtering in a guild of dominant
      freshwater macroinvertebrates?
AB  - Abiotic conditions have long been considered essential in structuring freshwater
      macroinvertebrate communities. Ecological drift, dispersal and biotic
      interactions also structure communities, and although these mechanisms are more
      difficult to detect, they may be of equal importance in natural communities.
      Here, we hypothesized that in 10 naturally replicated headwater streams in
      eastern Switzerland, locally dominant amphipod species would be associated with
      differences in environmental conditions. We conducted repeated surveys of
      amphipods and used a hierarchical joint species distribution model to assess the
      influence of different drivers on species co-occurrences. The species had unique
      environmental requirements, but a distinct spatial structure in their
      distributions was unrelated to habitat. Species co-occurred much less frequently
      than predicted by the model, which was surprising because laboratory and field
      evidence suggests they are capable of coexisting in equal densities. We suggest
      that niche preemption may limit their distribution and that a blocking effect
      related to the specific linear configuration of streams determines which species
      colonizes and dominates a given stream catchment, thus suggesting a new solution
      a long-standing conundrum in freshwater ecology.

PMID- 29643216
TI  - Feedback between environment and traits under selection in a seasonal
      environment: consequences for experimental evolution.
AB  - Batch cultures are frequently used in experimental evolution to study the
      dynamics of adaptation. Although they are generally considered to simply drive a
      growth rate increase, other fitness components can also be selected for. Indeed,
      recurrent batches form a seasonal environment where different phases repeat
      periodically and different traits can be under selection in the different
      seasons. Moreover, the system being closed, organisms may have a strong impact on
      the environment. Thus, the study of adaptation should take into account the
      environment and eco-evolutionary feedbacks. Using data from an experimental
      evolution on yeast Saccharomyces cerevisiae, we developed a mathematical model to
      understand which traits are under selection, and what is the impact of the
      environment for selection in a batch culture. We showed that two kinds of traits
      are under selection in seasonal environments: life-history traits, related to
      growth and mortality, but also transition traits, related to the ability to react
      to environmental changes. The impact of environmental conditions can be
      summarized by the length of the different seasons which weight selection on each
      trait: the longer a season is, the higher the selection on associated traits.
      Since phenotypes drive season length, eco-evolutionary feedbacks emerge. Our
      results show how evolution in successive batches can affect season lengths and
      strength of selection on different traits.

PMID- 29643218
TI  - Maternal effects impact decision-making in a viviparous lizard.
AB  - Stressful conditions experienced during early development can have deleterious
      effects on offspring morphology, physiology and behaviour. However, few studies
      have examined how developmental stress influences an individual's cognitive
      phenotype. Using a viviparous lizard, we show that the availability of food
      resources to a mother during gestation influences a key component of her
      offspring's cognitive phenotype: their decision-making. Offspring from females
      who experienced low resource availability during gestation did better in an anti
      predatory task that relied on spatial associations to guide their decisions,
      whereas offspring from females who experienced high resource availability during
      gestation did better in a foraging task that relied on colour associations to
      inform their decisions. This shows that the prenatal environment can influence
      decision-making in animals, a cognitive trait with functional implications later
      in life.

PMID- 29643217
TI  - Human, animal and environmental contributors to antibiotic resistance in low
      resource settings: integrating behavioural, epidemiological and One Health
      approaches.
AB  - Antibiotic resistance (ABR) is recognized as a One Health challenge because of
      the rapid emergence and dissemination of resistant bacteria and genes among
      humans, animals and the environment on a global scale. However, there is a
      paucity of research assessing ABR contemporaneously in humans, animals and the
      environment in low-resource settings. This critical review seeks to identify the
      extent of One Health research on ABR in low- and middle-income countries (LMICs).
      Existing research has highlighted hotspots for environmental contamination; food
      animal production systems that are likely to harbour reservoirs or promote
      transmission of ABR as well as high and increasing human rates of colonization
      with ABR commensal bacteria such as Escherichia coli However, very few studies
      have integrated all three components of the One Health spectrum to understand the
      dynamics of transmission and the prevalence of community-acquired resistance in
      humans and animals. Microbiological, epidemiological and social science research
      is needed at community and population levels across the One Health spectrum in
      order to fill the large gaps in knowledge of ABR in low-resource settings.

PMID- 29643219
TI  - Shyer and larger bird species show more reduced fear of humans when living in
      urban environments.
AB  - As the natural habitats of many species are degraded or disappear, there is scope
      for these species to be established in urban habitats. To ease the establishment
      and maintenance of urban populations of more species we need to better understand
      what degree of phenotypical change to expect as different species transition into
      urban environments. During the first stages of urban colonization, behavioural
      changes such as an increase in boldness are particularly important. A consistent
      response in urban populations is to decrease the distance at which individuals
      flee from an approaching human (flight initiation distance, or FID). Performing a
      phylogenetic generalized least-squares (PGLS) analysis on 130 avian species, I
      found that the largest changes in FID between rural and urban populations occur
      in species that are larger-bodied and naturally shy (higher rural FID), two
      phenotypic traits that are not normally associated with urban colonizers. More
      unlikely species may thus be able to colonize urban environments, especially if
      we design cities in ways that promote such urban colonizations.

PMID- 29643220
TI  - Mesotocin influences pinyon jay prosociality.
AB  - Many species exhibit prosocial behaviour, in which one individual's actions
      benefit another individual, often without an immediate benefit to itself. The
      neuropeptide oxytocin is an important hormonal mechanism influencing prosociality
      in mammals, but it is unclear whether the avian homologue mesotocin plays a
      similar functional role in birds. Here, we experimentally tested prosociality in
      pinyon jays (Gymnorhinus cyanocephalus), a highly social corvid species that
      spontaneously shares food with others. First, we measured prosocial preferences
      in a prosocial choice task with two different pay-off distributions: Prosocial
      trials delivered food to both the subject and either an empty cage or a partner
      bird, whereas Altruism trials delivered food only to an empty cage or a partner
      bird (none to subject). In a second experiment, we examined whether administering
      mesotocin influenced prosocial preferences. Compared to choices in a control
      condition, we show that subjects voluntarily delivered food rewards to partners,
      but only when also receiving food for themselves (Prosocial trials), and
      administration of high levels of mesotocin increased these behaviours. Thus, in
      birds, mesotocin seems to play a similar functional role in facilitating
      prosocial behaviours as oxytocin does in mammals, suggesting an evolutionarily
      conserved hormonal mechanism for prosociality.

PMID- 29643221
TI  - A variational approach to niche construction.
AB  - In evolutionary biology, niche construction is sometimes described as a genuine
      evolutionary process whereby organisms, through their activities and regulatory
      mechanisms, modify their environment such as to steer their own evolutionary
      trajectory, and that of other species. There is ongoing debate, however, on the
      extent to which niche construction ought to be considered a bona fide
      evolutionary force, on a par with natural selection. Recent formulations of the
      variational free-energy principle as applied to the life sciences describe the
      properties of living systems, and their selection in evolution, in terms of
      variational inference. We argue that niche construction can be described using a
      variational approach. We propose new arguments to support the niche construction
      perspective, and to extend the variational approach to niche construction to
      current perspectives in various scientific fields.

PMID- 29643222
TI  - In vivo characterization of bivalve larval shells: a confocal Raman microscopy
      study.
AB  - In vivo confocal Raman microscopy (CRM), polarized light microscopy and Fourier
      transform infrared spectroscopy (FTIR) were used to determine if a significant
      amount of amorphous calcium carbonate (ACC) exists within larval shells of Baltic
      mytilid mussels (Mytilus edulis-like) and whether the amount of ACC varies during
      larval development. No evidence for ACC was found from the onset of shell
      deposition at 21 h post-fertilization (hpf) until 48 hpf. Larval Mytilus shells
      were crystalline from 21 hpf onwards and exhibited CRM and FTIR peaks
      characteristic of aragonite. Prior to shell deposition at 21 hpf, no evidence for
      carbonates was observed through in vivo CRM. We further analysed the composition
      of larval shells in three other bivalve species, Mercenaria mercenaria,
      Crassostrea gigas and Crassostrea virginica and observed no evidence for ACC,
      which is in contrast to previous work on the same species. Our findings indicate
      that larval bivalve shells are composed of crystalline aragonite and we
      demonstrate that conflicting results are related to sub-optimal measurements and
      misinterpretation of CRM spectra. Our results demonstrate that the common
      perception that ACC generally occurs as a stable and abundant precursor during
      larval bivalve calcification needs to be critically reviewed.

PMID- 29643223
TI  - Nerve regeneration in the cephalopod mollusc Octopus vulgaris: label-free
      multiphoton microscopy as a tool for investigation.
AB  - Octopus and cephalopods are able to regenerate injured tissues. Recent
      advancements in the study of regeneration in cephalopods appear promising
      encompassing different approaches helping to decipher cellular and molecular
      machinery involved in the process. However, lack of specific markers to
      investigate degenerative/regenerative phenomena and inflammatory events occurring
      after damage is limiting these studies. Label-free multiphoton microscopy is
      applied for the first time to the transected pallial nerve of Octopus vulgaris
      Various optical contrast methods including coherent anti-Stokes Raman scattering
      (CARS), endogenous two-photon excited fluorescence (TPEF) and second harmonic
      generation (SHG) have been used. We detected cells and structures often not
      revealed with classical staining methods. CARS highlighted the involvement of
      haemocytes in building up scar tissue; CARS and TPEF facilitated the
      identification of degenerating fibres; SHG allowed visualization of fibrillary
      collagen, revealing the formation of a connective tissue bridge between the nerve
      stumps, likely involved in axon guidance. Using label-free multiphoton
      microscopy, we studied the regenerative events in octopus without using any other
      labelling techniques. These imaging methods provided extremely helpful morpho
      chemical information to describe regeneration events. The techniques applied here
      are species-specific independent and should facilitate the comparison among
      various animal species.

PMID- 29643225
TI  - Understanding/unravelling carotenoid excited singlet states.
AB  - Carotenoids are essential light-harvesting pigments in natural photosynthesis.
      They absorb in the blue-green region of the solar spectrum and transfer the
      absorbed energy to (bacterio-)chlorophylls, and thus expand the wavelength range
      of light that is able to drive photosynthesis. This process is an example of
      singlet-singlet excitation energy transfer, and carotenoids serve to enhance the
      overall efficiency of photosynthetic light reactions. The photochemistry and
      photophysics of carotenoids have often been interpreted by referring to those of
      simple polyene molecules that do not possess any functional groups. However, this
      may not always be wise because carotenoids usually have a number of functional
      groups that induce the variety of photochemical behaviours in them. These
      differences can also make the interpretation of the singlet excited states of
      carotenoids very complicated. In this article, we review the properties of the
      singlet excited states of carotenoids with the aim of producing as coherent a
      picture as possible of what is currently known and what needs to be learned.

PMID- 29643224
TI  - Long-range proton-coupled electron transfer in biological energy conversion:
      towards mechanistic understanding of respiratory complex I.
AB  - Biological energy conversion is driven by efficient enzymes that capture, store
      and transfer protons and electrons across large distances. Recent advances in
      structural biology have provided atomic-scale blueprints of these types of
      remarkable molecular machinery, which together with biochemical, biophysical and
      computational experiments allow us to derive detailed energy transduction
      mechanisms for the first time. Here, I present one of the most intricate and
      least understood types of biological energy conversion machinery, the respiratory
      complex I, and how its redox-driven proton-pump catalyses charge transfer across
      approximately 300 A distances. After discussing the functional elements of
      complex I, a putative mechanistic model for its action-at-a-distance effect is
      presented, and functional parallels are drawn to other redox- and light-driven
      ion pumps.

PMID- 29643226
TI  - Identification of a bet-hedging network motif generating noise in hormone
      concentrations and germination propensity in Arabidopsis.
AB  - Plants have evolved to exploit stochasticity to hedge bets and ensure robustness
      to varying environments between generations. In agriculture, environments are
      more controlled, and this evolved variability decreases potential yields, posing
      agronomic and food security challenges. Understanding how plant cells generate
      and harness noise thus presents options for engineering more uniform crop
      performance. Here, we use stochastic chemical kinetic modelling to analyse a
      hormone feedback signalling motif in Arabidopsis thaliana seeds that can generate
      tunable levels of noise in the hormone ABA, governing germination propensity. The
      key feature of the motif is simultaneous positive feedback regulation of both ABA
      production and degradation pathways, allowing tunable noise while retaining a
      constant mean level. We uncover surprisingly rich behaviour underlying the
      control of levels of, and noise in, ABA abundance. We obtain approximate analytic
      solutions for steady-state hormone level means and variances under general
      conditions, showing that antagonistic self-promoting and self-repressing
      interactions can together be tuned to induce noise while preserving mean hormone
      levels. We compare different potential architectures for this 'random output
      generator' with the motif found in Arabidopsis, and report the requirements for
      tunable control of noise in each case. We identify interventions that may
      facilitate large decreases in variability in germination propensity, in
      particular, the turnover of signalling intermediates and the sensitivity of
      synthesis and degradation machinery, as potentially valuable crop engineering
      targets.

PMID- 29643227
TI  - Voltage and pH sensing by the voltage-gated proton channel, HV1.
AB  - Voltage-gated proton channels are unique ion channels, membrane proteins that
      allow protons but no other ions to cross cell membranes. They are found in
      diverse species, from unicellular marine life to humans. In all cells, their
      function requires that they open and conduct current only under certain
      conditions, typically when the electrochemical gradient for protons is outwards.
      Consequently, these proteins behave like rectifiers, conducting protons out of
      cells. Their activity has electrical consequences and also changes the pH on both
      sides of the membrane. Here we summarize what is known about the way these
      proteins sense the membrane potential and the pH inside and outside the cell.
      Currently, it is hypothesized that membrane potential is sensed by permanently
      charged arginines (with very high pKa) within the protein, which results in parts
      of the protein moving to produce a conduction pathway. The mechanism of pH
      sensing appears to involve titratable side chains of particular amino acids. For
      this purpose their pKa needs to be within the operational pH range. We propose a
      'counter-charge' model for pH sensing in which electrostatic interactions within
      the protein are selectively disrupted by protonation of internally or externally
      accessible groups.

PMID- 29643230
TI  - The systemic response to surgery triggers the outgrowth of distant immune
      controlled tumors in mouse models of dormancy.
AB  - Patients undergoing surgical resection of primary breast tumors confront a risk
      for metastatic recurrence that peaks sharply 12 to 18 months after surgery. The
      cause of early metastatic relapse in breast cancer has long been debated, with
      many ascribing these relapses to the natural progression of the disease. Others
      have proposed that some aspect of surgical tumor resection triggers the outgrowth
      of otherwise-dormant metastases, leading to the synchronous pattern of relapse.
      Clinical data cannot distinguish between these hypotheses, and previous
      experimental approaches have not provided clear answers. Such uncertainty hinders
      the development and application of therapeutic approaches that could potentially
      reduce early metastatic relapse. We describe an experimental model system that
      definitively links surgery and the subsequent wound-healing response to the
      outgrowth of tumor cells at distant anatomical sites. Specifically, we find that
      the systemic inflammatory response induced after surgery promotes the emergence
      of tumors whose growth was otherwise restricted by a tumor-specific T cell
      response. Furthermore, we demonstrate that perioperative anti-inflammatory
      treatment markedly reduces tumor outgrowth in this model, suggesting that similar
      approaches might substantially reduce early metastatic recurrence in breast
      cancer patients.

PMID- 29643228
TI  - Dual inhibition of MDMX and MDM2 as a therapeutic strategy in leukemia.
AB  - The tumor suppressor p53 is often inactivated via its interaction with endogenous
      inhibitors mouse double minute 4 homolog (MDM4 or MDMX) or mouse double minute 2
      homolog (MDM2), which are frequently overexpressed in patients with acute myeloid
      leukemia (AML) and other cancers. Pharmacological disruption of both of these
      interactions has long been sought after as an attractive strategy to fully
      restore p53-dependent tumor suppressor activity in cancers with wild-type p53.
      Selective targeting of this pathway has thus far been limited to MDM2-only small
      molecule inhibitors, which lack affinity for MDMX. We demonstrate that dual
      MDMX/MDM2 inhibition with a stapled alpha-helical peptide (ALRN-6924), which has
      recently entered phase I clinical testing, produces marked antileukemic effects.
      ALRN-6924 robustly activates p53-dependent transcription at the single-cell and
      single-molecule levels and exhibits biochemical and molecular biological on
      target activity in leukemia cells in vitro and in vivo. Dual MDMX/MDM2 inhibition
      by ALRN-6924 inhibits cellular proliferation by inducing cell cycle arrest and
      apoptosis in cell lines and primary AML patient cells, including leukemic stem
      cell-enriched populations, and disrupts functional clonogenic and serial
      replating capacity. Furthermore, ALRN-6924 markedly improves survival in AML
      xenograft models. Our study provides mechanistic insight to support further
      testing of ALRN-6924 as a therapeutic approach in AML and other cancers with wild
      type p53.

PMID- 29643229
TI  - T cell-induced CSF1 promotes melanoma resistance to PD1 blockade.
AB  - Colony-stimulating factor 1 (CSF1) is a key regulator of monocyte/macrophage
      differentiation that sustains the protumorigenic functions of tumor-associated
      macrophages (TAMs). We show that CSF1 is expressed in human melanoma, and
      patients with metastatic melanoma have increased CSF1 in blood compared to
      healthy subjects. In tumors, CSF1 expression correlated with the abundance of
      CD8+ T cells and CD163+ TAMs. Human melanoma cell lines consistently produced
      CSF1 after exposure to melanoma-specific CD8+ T cells or T cell-derived cytokines
      in vitro, reflecting a broadly conserved mechanism of CSF1 induction by activated
      CD8+ T cells. Mining of publicly available transcriptomic data sets suggested co
      enrichment of CD8+ T cells with CSF1 or various TAM-specific markers in human
      melanoma, which was associated with nonresponsiveness to programmed cell death
      protein 1 (PD1) checkpoint blockade in a smaller patient cohort. Combination of
      anti-PD1 and anti-CSF1 receptor (CSF1R) antibodies induced the regression of
      BRAFV600E -driven, transplant mouse melanomas, a result that was dependent on the
      effective elimination of TAMs. Collectively, these data implicate CSF1 induction
      as a CD8+ T cell-dependent adaptive resistance mechanism and show that
      simultaneous CSF1R targeting may be beneficial in melanomas refractory to immune
      checkpoint blockade and, possibly, other T cell-based therapies.

PMID- 29643231
TI  - Personalized cancer vaccine effectively mobilizes antitumor T cell immunity in
      ovarian cancer.
AB  - We conducted a pilot clinical trial testing a personalized vaccine generated by
      autologous dendritic cells (DCs) pulsed with oxidized autologous whole-tumor cell
      lysate (OCDC), which was injected intranodally in platinum-treated, immunotherapy
      naive, recurrent ovarian cancer patients. OCDC was administered alone (cohort 1,
      n = 5), in combination with bevacizumab (cohort 2, n = 10), or bevacizumab plus
      low-dose intravenous cyclophosphamide (cohort 3, n = 10) until disease
      progression or vaccine exhaustion. A total of 392 vaccine doses were administered
      without serious adverse events. Vaccination induced T cell responses to
      autologous tumor antigen, which were associated with significantly prolonged
      survival. Vaccination also amplified T cell responses against mutated neoepitopes
      derived from nonsynonymous somatic tumor mutations, and this included priming of
      T cells against previously unrecognized neoepitopes, as well as novel T cell
      clones of markedly higher avidity against previously recognized neoepitopes. We
      conclude that the use of oxidized whole-tumor lysate DC vaccine is safe and
      effective in eliciting a broad antitumor immunity, including private neoantigens,
      and warrants further clinical testing.

PMID- 29643233
TI  - Hematopoietic stem cell transplantation in its 60s: A platform for cellular
      therapies.
AB  - Over the last 60 years, more than a million patients received hematopoietic cell
      transplantation. Having incorporated multiple changes in clinical practices, it
      remains a complex procedure facing a dual challenge: cure of the underlying
      disease and prevention of relapse while controlling potentially severe
      complications. Improved understanding of underlying biological processes resulted
      in the design of innovative therapies engineered from defined cell populations
      and testing of these therapies as addition or substitution at virtually every
      step of the procedure. This review provides an overview of these developments,
      many of them now applied outside the historical field of hematopoietic cell
      transplantation.

PMID- 29643232
TI  - Increased neutrophil extracellular trap formation promotes thrombosis in
      myeloproliferative neoplasms.
AB  - Thrombosis is a major cause of morbidity and mortality in Philadelphia chromosome
      negative myeloproliferative neoplasms (MPNs), clonal disorders of hematopoiesis
      characterized by activated Janus kinase (JAK)-signal transducer and activator of
      transcription (STAT) signaling. Neutrophil extracellular trap (NET) formation, a
      component of innate immunity, has been linked to thrombosis. We demonstrate that
      neutrophils from patients with MPNs are primed for NET formation, an effect
      blunted by pharmacological inhibition of JAK signaling. Mice with conditional
      knock-in of Jak2V617F, the most common molecular driver of MPN, have an increased
      propensity for NET formation and thrombosis. Inhibition of JAK-STAT signaling
      with the clinically available JAK2 inhibitor ruxolitinib abrogated NET formation
      and reduced thrombosis in a deep vein stenosis murine model. We further show that
      expression of PAD4, a protein required for NET formation, is increased in
      JAK2V617F-expressing neutrophils and that PAD4 is required for Jak2V617F-driven
      NET formation and thrombosis in vivo. Finally, in a population study of more than
      10,000 individuals without a known myeloid disorder, JAK2V617F-positive clonal
      hematopoiesis was associated with an increased incidence of thrombosis. In
      aggregate, our results link JAK2V617F expression to NET formation and thrombosis
      and suggest that JAK2 inhibition may reduce thrombosis in MPNs through cell
      intrinsic effects on neutrophil function.

PMID- 29643234
TI  - Visualization of Arenavirus RNA Species in Individual Cells by Single-Molecule
      Fluorescence In Situ Hybridization Suggests a Model of Cyclical Infection and
      Clearance during Persistence.
AB  - Lymphocytic choriomeningitis mammarenavirus (LCMV) is an enveloped, negative
      strand RNA virus that causes serious disease in humans but establishes an
      asymptomatic, lifelong infection in reservoir rodents. Different models have been
      proposed to describe how arenaviruses regulate the replication and transcription
      of their bisegmented, single-stranded RNA genomes, particularly during persistent
      infection. However, these models were based largely on viral RNA profiling data
      derived from entire populations of cells. To better understand LCMV replication
      and transcription at the single-cell level, we established a high-throughput,
      single-molecule fluorescence in situ hybridization (smFISH) image acquisition and
      analysis pipeline and examined viral RNA species at discrete time points from
      virus entry through the late stages of persistent infection in vitro We observed
      the transcription of viral nucleoprotein and polymerase mRNAs from the incoming S
      and L segment genomic RNAs, respectively, within 1 h of infection, whereas the
      transcription of glycoprotein mRNA from the S segment antigenome required ~4 to 6
      h. This confirms the temporal separation of viral gene expression expected due to
      the ambisense coding strategy of arenaviruses and also suggests that antigenomic
      RNA contained in virions is not transcriptionally active upon entry. Viral
      replication and transcription peaked at 36 h postinfection, followed by a
      progressive loss of viral RNAs over the next several days. During persistence,
      the majority of cells showed repeating cyclical waves of viral transcription and
      replication followed by the clearance of viral RNA. Thus, our data support a
      model of LCMV persistence whereby infected cells can spontaneously clear
      infection and become reinfected by viral reservoir cells that remain in the
      population.IMPORTANCE Arenaviruses are human pathogens that can establish
      asymptomatic, lifelong infections in their rodent reservoirs. Several models have
      been proposed to explain how arenavirus spread is restricted within host rodents,
      including the periodic accumulation and loss of replication-competent, but
      transcriptionally incompetent, viral genomes. A limitation of previous studies
      was the inability to enumerate viral RNA species at the single-cell level. We
      developed a high-throughput, smFISH assay and used it to quantitate lymphocytic
      choriomeningitis mammarenavirus (LCMV) replicative and transcriptional RNA
      species in individual cells at distinct time points following infection. Our
      findings support a model whereby productively infected cells can clear infection,
      including viral RNAs and antigen, and later be reinfected. This information
      improves our understanding of the timing and possible regulation of LCMV genome
      replication and transcription during infection. Importantly, the smFISH assay and
      data analysis pipeline developed here is easily adaptable to other RNA viruses.

PMID- 29643235
TI  - Developing and Evaluating Inhibitors against the RNase H Active Site of HIV-1
      Reverse Transcriptase.
AB  - We tested three compounds for their ability to inhibit the RNase H (RH) and
      polymerase activities of HIV-1 reverse transcriptase (RT). A high-resolution
      crystal structure (2.2 A) of one of the compounds showed that it chelates the two
      magnesium ions at the RH active site; this prevents the RH active site from
      interacting with, and cleaving, the RNA strand of an RNA-DNA heteroduplex. The
      compounds were tested using a variety of substrates: all three compounds
      inhibited the polymerase-independent RH activity of HIV-1 RT. Time-of-addition
      experiments showed that the compounds were more potent if they were bound to RT
      before the nucleic acid substrate was added. The compounds significantly
      inhibited the site-specific cleavage required to generate the polypurine tract
      (PPT) RNA primer that initiates the second strand of viral DNA synthesis. The
      compounds also reduced the polymerase activity of RT; this ability was a result
      of the compounds binding to the RH active site. These compounds appear to be
      relatively specific; they do not inhibit either Escherichia coli RNase HI or
      human RNase H2. The compounds inhibit the replication of an HIV-1-based vector in
      a one-round assay, and their potencies were only modestly decreased by mutations
      that confer resistance to integrase strand transfer inhibitors (INSTIs),
      nucleoside analogs, or nonnucleoside RT inhibitors (NNRTIs), suggesting that
      their ability to block HIV replication is related to their ability to block RH
      cleavage. These compounds appear to be useful leads that can be used to develop
      more potent and specific compounds.IMPORTANCE Despite advances in HIV-1
      treatment, drug resistance is still a problem. Of the four enzymatic activities
      found in HIV-1 proteins (protease, RT polymerase, RT RNase H, and integrase),
      only RNase H has no approved therapeutics directed against it. This new target
      could be used to design and develop new classes of inhibitors that would suppress
      the replication of the drug-resistant variants that have been selected by the
      current therapeutics.

PMID- 29643236
TI  - Introduction of Viral Hemorrhagic Septicemia Virus into Freshwater Cultured
      Rainbow Trout Is Followed by Bursts of Adaptive Evolution.
AB  - Viral hemorrhagic septicemia virus (VHSV), a rhabdovirus infecting teleost fish,
      has repeatedly crossed the boundary from marine fish species to freshwater
      cultured rainbow trout. These naturally replicated cross-species transmission
      events permit the study of general and repeatable evolutionary events occurring
      in connection with viral emergence in a novel host species. The purpose of the
      present study was to investigate the adaptive molecular evolution of the VHSV
      glycoprotein, one of the key virus proteins involved in viral emergence,
      following emergence from marine species into freshwater cultured rainbow trout. A
      comprehensive phylogenetic reconstruction of the complete coding region of the
      VHSV glycoprotein was conducted, and adaptive molecular evolution was
      investigated using a maximum likelihood approach to compare different codon
      substitution models allowing for heterogeneous substitution rate ratios among
      amino acid sites. Evidence of positive selection was detected at six amino acid
      sites of the VHSV glycoprotein, within the signal peptide, the confirmation
      dependent major neutralizing epitope, and the intracellular tail. Evidence of
      positive selection was found exclusively in rainbow trout-adapted virus isolates,
      and amino acid combinations found at the six sites under positive selection
      pressure differentiated rainbow trout- from non-rainbow trout-adapted isolates.
      Furthermore, four adaptive sites revealed signs of recurring identical changes
      across phylogenetic groups of rainbow trout-adapted isolates, suggesting that
      repeated VHSV emergence in freshwater cultured rainbow trout was established
      through convergent routes of evolution that are associated with immune
      escape.IMPORTANCE This study is the first to demonstrate that VHSV emergence from
      marine species into freshwater cultured rainbow trout has been accompanied by
      bursts of adaptive evolution in the VHSV glycoprotein. Furthermore, repeated
      detection of the same adaptive amino acid sites across phylogenetic groups of
      rainbow trout-adapted isolates indicates that adaptation to rainbow trout was
      established through parallel evolution. In addition, signals of convergent
      evolution toward the maintenance of genetic variation were detected in the
      conformation-dependent neutralizing epitope or in close proximity to disulfide
      bonds involved in the structural conformation of the neutralizing epitope,
      indicating adaptation to immune response-related genetic variation across
      freshwater cultured rainbow trout.

PMID- 29643238
TI  - JC Polyomavirus: Let's Please Respect Privacy.
AB  - JC polyomavirus was discovered in 1971, and its name was derived from the
      initials of the individual from whose brain tissue it was isolated. While most
      scientists refer to the virus properly, i.e., calling it JCV or JCPyV, there is a
      small but palpable number of scientists who refer to the virus by the full name
      of the patient from whom it was isolated. This practice should stop.

PMID- 29643237
TI  - The Functional Oligomeric State of Tegument Protein GP41 Is Essential for
      Baculovirus Budded Virion and Occlusion-Derived Virion Assembly.
AB  - gp41, one of the baculovirus core genes, encodes the only recognized tegument (O
      glycosylated) protein of the occlusion-derived virion (ODV) phenotype so far. A
      previous study using a temperature-sensitive Autographa californica multicapsid
      nucleopolyhedrovirus (AcMNPV) mutant showed that GP41 plays a crucial role in
      budded virion (BV) formation. However, the precise function of GP41 in the
      baculovirus replication cycle remains unclear. In this study, AcMNPV GP41 was
      found to accumulate around the ring zone (RZ) region within the infected nucleus
      and finally assembled into both BVs and ODVs. Deletion of gp41 from the AcMNPV
      genome showed that BVs were no longer formed and ODVs were no longer assembled,
      suggesting the essential role of this gene in baculovirus virion morphogenesis.
      In infected cells, besides the 42-kDa monomers, dimers and trimers were detected
      under nonreducing conditions, whereas only trimeric GP41 forms were selectively
      incorporated into BVs or ODVs. Mutations of all five cysteines in GP41
      individually had minor effects on GP41 oligomer formation, albeit certain
      mutations impaired infectious BV production, suggesting flexibility in the
      intermolecular disulfide bonding. Single mutations of key leucines within two
      predicted leucine zipper-like motifs did not interfere with GP41 oligomerization
      or BV and ODV formation, but double leucine mutations completely blocked
      oligomerization of GP41 and progeny BV production. In the latter case, the usual
      subcellular localization, especially RZ accumulation, of GP41 was abolished. The
      above findings clearly point out a close correlation between GP41 oligomerization
      and function and therefore highlight the oligomeric state as the functional form
      of GP41 in the baculovirus replication cycle.IMPORTANCE The tegument, which is
      sandwiched between the nucleocapsid and the virion envelope, is an important
      substructure of many enveloped viruses. It is composed of one or more proteins
      that have important functions during virus entry, replication, assembly, and
      egress. Unlike another large DNA virus (herpesvirus) that encodes an extensive
      set of tegument components, baculoviruses very likely exploit the major tegument
      protein, GP41, to execute functions in baculovirus virion morphogenesis and
      assembly. However, the function of this O-glycosylated baculovirus tegument
      protein remains largely unknown. In this study, we identified trimers as the
      functional structure of GP41 in baculovirus virion morphogenesis and showed that
      both disulfide bridging and protein-protein interactions via the two leucine
      zipper-like domains are involved in the formation of different oligomeric states.
      This study advances our understanding of the unique viral tegument protein GP41
      participating in the life cycle of baculoviruses.

PMID- 29643239
TI  - Kaposi's Sarcoma-Associated Herpesvirus mRNA Accumulation in Nuclear Foci Is
      Influenced by Viral DNA Replication and Viral Noncoding Polyadenylated Nuclear
      RNA.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV), like other herpesviruses,
      replicates within the nuclei of its human cell host and hijacks host machinery
      for expression of its genes. The activities that culminate in viral DNA synthesis
      and assembly of viral proteins into capsids physically concentrate in nuclear
      areas termed viral replication compartments. We sought to better understand the
      spatiotemporal regulation of viral RNAs during the KSHV lytic phase by examining
      and quantifying the subcellular localization of select viral transcripts. We
      found that viral mRNAs, as expected, localized to the cytoplasm throughout the
      lytic phase. However, dependent on active viral DNA replication, viral
      transcripts also accumulated in the nucleus, often in foci in and around
      replication compartments, independent of the host shutoff effect. Our data point
      to involvement of the viral long noncoding polyadenylated nuclear (PAN) RNA in
      the localization of an early, intronless viral mRNA encoding ORF59-58 to nuclear
      foci that are associated with replication compartments.IMPORTANCE Late in the
      lytic phase, mRNAs from Kaposi's sarcoma-associated herpesvirus accumulate in the
      host cell nucleus near viral replication compartments, centers of viral DNA
      synthesis and virion production. This work contributes spatiotemporal data on
      herpesviral mRNAs within the lytic host cell and suggests a mechanism for viral
      RNA accumulation. Our findings indicate that the mechanism is independent of the
      host shutoff effect and splicing but dependent on active viral DNA synthesis and
      in part on the viral noncoding RNA, PAN RNA. PAN RNA is essential for the viral
      life cycle, and its contribution to the nuclear accumulation of viral messages
      may facilitate propagation of the virus.

PMID- 29643240
TI  - HIV Protease-Generated Casp8p41, When Bound and Inactivated by Bcl2, Is Degraded
      by the Proteasome.
AB  - HIV protease is known to cause cell death, which is dependent upon cleavage of
      procaspase 8. HIV protease cleavage of procaspase 8 generates Casp8p41, which
      directly binds Bak with nanomolar affinity, causing Bak activation and consequent
      cell death. Casp8p41 can also bind Bcl2 with nanomolar affinity, in which case
      cell death is averted. Central memory CD4 T cells express high levels of Bcl2,
      possibly explaining why those cells do not die when they reactivate HIV. Here, we
      determine that the Casp8p41-Bcl2 complex is polyubiquitinated and degraded by the
      proteasome. Ixazomib, a proteasome inhibitor in clinical use, blocks this
      pathway, increasing the abundance of Casp8p41 and causing more cells to die in a
      Casp8p41-dependent manner.IMPORTANCE The Casp8p41 pathway of cell death is unique
      to HIV-infected cells yet is blocked by Bcl2. Once bound by Bcl2, Casp8p41 is
      polyubiquitinated and degraded by the proteasome. Proteasome inhibition blocks
      degradation of Casp8p41, increasing Casp8p41 levels and causing more HIV-infected
      cells to die.

PMID- 29643241
TI  - Truncated CPSF6 Forms Higher-Order Complexes That Bind and Disrupt HIV-1 Capsid.
AB  - Cleavage and polyadenylation specificity factor 6 (CPSF6) is a human protein that
      binds HIV-1 capsid and mediates nuclear transport and integration targeting of
      HIV-1 preintegration complexes. Truncation of the protein at its C-terminal
      nuclear-targeting arginine/serine-rich (RS) domain produces a protein, CPSF6-358,
      that potently inhibits HIV-1 infection by targeting the capsid and inhibiting
      nuclear entry. To understand the molecular mechanism behind this restriction, the
      interaction between CPSF6-358 and HIV-1 capsid was characterized using in vitro
      and in vivo assays. Purified CPSF6-358 protein formed oligomers and bound in
      vitro-assembled wild-type (WT) capsid protein (CA) tubes, but not CA tubes
      containing a mutation in the putative binding site of CPSF6. Intriguingly,
      binding of CPSF6-358 oligomers to WT CA tubes physically disrupted the tubular
      assemblies into small fragments. Furthermore, fixed- and live-cell imaging showed
      that stably expressed CPSF6-358 forms cytoplasmic puncta upon WT HIV-1 infection
      and leads to capsid permeabilization. These events did not occur when the HIV-1
      capsid contained a mutation known to prevent CPSF6 binding, nor did they occur in
      the presence of a small-molecule inhibitor of capsid binding to CPSF6-358.
      Together, our in vitro biochemical and transmission electron microscopy data and
      in vivo intracellular imaging results provide the first direct evidence for an
      oligomeric nature of CPSF6-358 and suggest a plausible mechanism for restriction
      of HIV-1 infection by CPSF6-358.IMPORTANCE After entry into cells, the HIV-1
      capsid, which contains the viral genome, interacts with numerous host cell
      factors to facilitate crucial events required for replication, including
      uncoating. One such host cell factor, called CPSF6, is predominantly located in
      the cell nucleus and interacts with HIV-1 capsid. The interaction between CA and
      CPSF6 is critical during HIV-1 replication in vivo Truncation of CPSF6 leads to
      its localization to the cell cytoplasm and inhibition of HIV-1 infection. Here,
      we determined that truncated CPSF6 protein forms large higher-order complexes
      that bind directly to HIV-1 capsid, leading to its disruption. Truncated CPSF6
      expression in cells leads to premature capsid uncoating that is detrimental to
      HIV-1 infection. Our study provides the first direct evidence for an oligomeric
      nature of truncated CPSF6 and insights into the highly regulated process of HIV-1
      capsid uncoating.

PMID- 29643242
TI  - RIG-I-Like Receptor and Toll-Like Receptor Signaling Pathways Cause Aberrant
      Production of Inflammatory Cytokines/Chemokines in a Severe Fever with
      Thrombocytopenia Syndrome Virus Infection Mouse Model.
AB  - Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious
      disease caused by a tick-borne phlebovirus of the family Bunyaviridae, SFTS virus
      (SFTSV). Wild-type and type I interferon (IFN-I) receptor 1-deficient (IFNAR1-/-)
      mice have been established as nonlethal and lethal models of SFTSV infection,
      respectively. However, the mechanisms of IFN-I production in vivo and the factors
      causing the lethal disease are not well understood. Using bone marrow-chimeric
      mice, we found that IFN-I signaling in hematopoietic cells was essential for
      survival of lethal SFTSV infection. The disruption of IFN-I signaling in
      hematopoietic cells allowed an increase in viral loads in serum and produced an
      excess of multiple inflammatory cytokines and chemokines. The production of IFN-I
      and inflammatory cytokines was abolished by deletion of the signaling molecules
      IPS-1 and MyD88, essential for retinoic acid-inducible gene I (RIG-I)-like
      receptor (RLR) and Toll-like receptor (TLR) signaling, respectively. However, IPS
      1-/- MyD88-/- mice exhibited resistance to lethal SFTS with a moderate viral load
      in serum. Taken together, these results indicate that adequate activation of RLR
      and TLR signaling pathways under low to moderate levels of viremia contributed to
      survival through the IFN-I-dependent antiviral response during SFTSV infection,
      whereas overactivation of these signaling pathways under high levels of viremia
      resulted in abnormal induction of multiple inflammatory cytokines and chemokines,
      causing the lethal disease.IMPORTANCE SFTSV causes a severe infectious disease in
      humans, with a high fatality rate of 12 to 30%. To know the pathogenesis of the
      virus, we need to clarify the innate immune response as a front line of defense
      against viral infection. Here, we report that a lethal animal model showed
      abnormal induction of multiple inflammatory cytokines and chemokines by an
      uncontrolled innate immune response, which triggered the lethal SFTS. Our
      findings suggest a new strategy to target inflammatory humoral factors to treat
      patients with severe SFTS. Furthermore, this study may help the investigation of
      other tick-borne viruses.

PMID- 29643243
TI  - Inefficient HIV-1 trans Infection of CD4+ T Cells by Macrophages from HIV-1
      Nonprogressors Is Associated with Altered Membrane Cholesterol and DC-SIGN.
AB  - Professional antigen-presenting cells (APC; myeloid dendritic cells [DC] and
      macrophages [MPhi]; B lymphocytes) mediate highly efficient HIV-1 infection of
      CD4+ T cells, termed trans infection, that could contribute to HIV-1
      pathogenesis. We have previously shown that lower cholesterol content in DC and B
      lymphocytes is associated with a lack of HIV-1 trans infection in HIV-1-infected
      nonprogressors (NP). Here, we assessed whether HIV-1 trans infection mediated by
      another major APC, MPhi, is deficient in NP due to altered cholesterol
      metabolism. When comparing healthy HIV-1 seronegatives (SN), rapid progressors
      (PR), and NP, we found that monocyte-derived MPhi from NP did not mediate HIV-1
      trans infection of autologous CD4+ T cells, in contrast to efficient trans
      infection mediated by SN and PR MPhi. MPhi trans infection efficiency was
      directly associated with the number of DC-specific intercellular adhesion
      molecule-3-grabbing nonintegrin (DC-SIGN)-expressing MPhi. Significantly fewer NP
      MPhi expressed DC-SIGN. Unesterified (free) cholesterol in MPhi cell membranes
      and lipid rafting was significantly lower in NP than PR, as was virus
      internalization in early endosomes. Furthermore, simvastatin (SIMV) decreased the
      subpopulation of DC-SIGN+ MPhi as well as cis and trans infection. Notably, SIMV
      decreased cell membrane cholesterol and led to lipid raft dissociation,
      effectively mimicking the incompetent APC trans infection environment
      characteristic of NP. Our data support that DC-SIGN and membrane cholesterol are
      central to MPhi trans infection, and a lack of these limits HIV-1 disease
      progression. Targeting the ability of MPhi to drive HIV-1 dissemination in trans
      could enhance HIV-1 therapeutic strategies.IMPORTANCE Despite the success of
      combination antiretroviral therapy, neither a vaccine nor a cure for HIV
      infection has been developed, demonstrating a need for novel prophylactic and
      therapeutic strategies. Here, we show that efficiency of MPhi-mediated HIV trans
      infection of CD4+ T cells is a unique characteristic associated with control of
      disease progression, and it is impaired in HIV-infected NP. In vitro treatment of
      MPhi from healthy donors with SIMV lowers their cholesterol content, which
      results in a strongly reduced trans infection ability, similar to the levels of
      MPhi from NP. Taken together, our data support the hypothesis that MPhi-mediated
      HIV-1 trans infection plays a role in HIV infection and disease progression and
      demonstrate that the use of SIMV to decrease this mechanism of virus transfer
      should be considered for future HIV therapeutic development.

PMID- 29643244
TI  - SUN1 Regulates HIV-1 Nuclear Import in a Manner Dependent on the Interaction
      between the Viral Capsid and Cellular Cyclophilin A.
AB  - Human immunodeficiency virus type 1 (HIV-1) can infect nondividing cells via
      passing through the nuclear pore complex. The nuclear membrane-imbedded protein
      SUN2 was recently reported to be involved in the nuclear import of HIV-1. Whether
      SUN1, which shares many functional similarities with SUN2, is involved in this
      process remained to be explored. Here we report that overexpression of SUN1
      specifically inhibited infection by HIV-1 but not that by simian immunodeficiency
      virus (SIV) or murine leukemia virus (MLV). Overexpression of SUN1 did not affect
      reverse transcription but led to reduced accumulation of the 2-long-terminal
      repeat (2-LTR) circular DNA and integrated viral DNA, suggesting a block in the
      process of nuclear import. HIV-1 CA was mapped as a determinant for viral
      sensitivity to SUN1. Treatment of SUN1-expressing cells with cyclosporine (CsA)
      significantly reduced the sensitivity of the virus to SUN1, and an HIV-1 mutant
      containing CA-G89A, which does not interact with cyclophilin A (CypA), was
      resistant to SUN1 overexpression. Downregulation of endogenous SUN1 inhibited the
      nuclear entry of the wild-type virus but not that of the G89A mutant. These
      results indicate that SUN1 participates in the HIV-1 nuclear entry process in a
      manner dependent on the interaction of CA with CypA.IMPORTANCE HIV-1 infects both
      dividing and nondividing cells. The viral preintegration complex (PIC) can enter
      the nucleus through the nuclear pore complex. It has been well known that the
      viral protein CA plays an important role in determining the pathways by which the
      PIC enters the nucleus. In addition, the interaction between CA and the cellular
      protein CypA has been reported to be important in the selection of nuclear entry
      pathways, though the underlying mechanisms are not very clear. Here we show that
      both SUN1 overexpression and downregulation inhibited HIV-1 nuclear entry. CA
      played an important role in determining the sensitivity of the virus to SUN1: the
      regulatory activity of SUN1 toward HIV-1 relied on the interaction between CA and
      CypA. These results help to explain how SUN1 is involved in the HIV-1 nuclear
      entry process.

PMID- 29643245
TI  - Recombinant Porcine Reproductive and Respiratory Syndrome Virus Expressing
      Membrane-Bound Interleukin-15 as an Immunomodulatory Adjuvant Enhances NK and
      gammadelta T Cell Responses and Confers Heterologous Protection.
AB  - Cytokines are often used as adjuvants to improve vaccine immunogenicity, since
      they are important in initiating and shaping the immune response. The available
      commercial modified live-attenuated vaccines (MLVs) against porcine reproductive
      and respiratory syndrome virus (PRRSV) are unable to mount sufficient
      heterologous protection, as they typically induce weak innate and inadequate T
      cell responses. In this study, we investigated the immunogenicity and vaccine
      efficacy of recombinant PRRSV MLVs incorporated with the porcine cytokine
      interleukin-15 (IL-15) or IL-18 gene fused to a glycosylphosphatidylinositol
      (GPI) modification signal that can anchor the cytokines to the cell membrane. We
      demonstrated that both cytokines were successfully expressed on the cell membrane
      of porcine alveolar macrophages after infection with recombinant MLVs. Pigs
      vaccinated with recombinant MLVs or the parental Suvaxyn MLV had significantly
      reduced lung lesions and viral RNA loads in the lungs after heterologous
      challenge with the PRRSV NADC20 strain. The recombinant MLVs SUV-IL-15 and SUV-IL
      18 recovered the inhibition of the NK cell response seen with Suvaxyn MLV. The
      recombinant MLV SUV-IL-15 significantly increased the numbers of gamma interferon
      (IFN-gamma)-producing cells in circulation at 49 days postvaccination (dpv),
      especially for IFN-gamma-producing CD4- CD8+ T cells and gammadelta T cells,
      compared to the Suvaxyn MLV and SUV-IL-18. Additionally, MLV SUV-IL-15-vaccinated
      pigs also had elevated levels of gammadelta T cell responses observed at 7 dpv,
      49 dpv, and 7 days postchallenge. These data demonstrate that the recombinant MLV
      expressing membrane-bound IL-15 enhances NK and T cell immune responses after
      vaccination and confers improved heterologous protection, although this was not
      statistically significant compared to the parental MLV.IMPORTANCE Porcine
      reproductive and respiratory syndrome (PRRS) has arguably been the most
      economically important global swine disease, causing immense economic losses
      worldwide. The available commercial modified live-attenuated vaccines (MLVs)
      against PRRS virus (PRRSV) are generally effective against only homologous or
      closely related virus strains but are ineffective against heterologous strains,
      partially due to the insufficient immune response induced by the vaccine virus.
      To improve the immunogenicity of MLVs, in this study, we present a novel approach
      of using porcine IL-15 or IL-18 as an adjuvant by directly incorporating its
      encoding gene into a PRRSV MLV and expressing it as an adjuvant. Importantly, we
      directed the expression of the incorporated cytokines to the cell membrane
      surface by fusing the genes with a membrane-targeting signal from CD59. The
      recombinant MLV virus expressing the membrane-bound IL-15 cytokine greatly
      enhanced NK cell and gammadelta T cell responses and also conferred improved
      protection against heterologous challenge with the PRRSV NADC20 strain.

PMID- 29643246
TI  - Dynamics of Simian Immunodeficiency Virus Two-Long-Terminal-Repeat Circles in the
      Presence and Absence of CD8+ Cells.
AB  - CD8+ cells play a key role in human immunodeficiency virus (HIV)/simian
      immunodeficiency virus (SIV) infection, but their specific mechanism(s) of action
      in controlling the virus is unclear. Two-long-terminal-repeat (2-LTR) circles are
      extrachromosomal products generated upon failed integration of HIV/SIV. To
      understand the specific effects of CD8+ cells on infected cells, we analyzed the
      dynamics of 2-LTR circles in SIVmac251-infected rhesus macaques (RMs) treated
      with an integrase inhibitor (INT). Twenty RMs underwent CD8+ cell depletion and
      received raltegravir (RAL) monotherapy or a combination of both. Blood, lymph
      nodes (LNs), and gut biopsy specimens were routinely sampled. Plasma viral loads
      (pVLs) and 2-LTR circles from peripheral blood mononuclear cells (PBMCs) and LN
      lymphocytes were measured with quantitative reverse transcription-PCR (qRT-PCR).
      In the CD8 depletion group, an ~1-log increase in pVLs and a slow increase in
      PBMC 2-LTRs occurred following depletion. In the INT group, a strong decline in
      pVLs upon treatment initiation and no change in 2-LTR levels were observed. In
      the INT and CD8+ cell depletion group, an increase in pVLs following CD8
      depletion similar to that in the CD8 depletion group was observed, with a modest
      decline following INT initiation, and 2-LTR circles significantly increased in
      PBMCs and LNs. Analyzing the 2-LTR data across all treatment groups with a
      mathematical model indicates that the data best support an effect of CD8+ cells
      in killing cells prior to viral integration. Sensitivity analyses of these
      results confirm that effect but also allow for additional effects, which the data
      do not discriminate well. Overall, we show that INT does not significantly
      increase the levels of 2-LTR circles. However, CD8+ cell depletion increases the
      2-LTR levels, which are enhanced in the presence of an INT.IMPORTANCE CD8+ T
      cells play an essential role in controlling HIV and SIV infection, but the
      specific mechanisms involved remain poorly understood. Due to failed viral
      infection, HIV and SIV can form 2-LTR extrachromosomal circles that can be
      quantified. We present novel data on the dynamics of these 2-LTR forms in a SIV
      infected macaque model under three different treatment conditions: depletion of
      CD8+ cells, administration of the integrase inhibitor in a monotherapy, which
      favors the formation of 2-LTR circles, and a combination of the two treatments.
      We used a new mathematical model to help interpret the data, and the results
      suggest that CD8+ cells exert a killing effect on infected cells prior to virus
      integration. These results provide new insights into the mechanisms of action of
      CD8+ cells in SIV infection. Confirmation of our results would be an important
      step in understanding immune control of HIV.

PMID- 29643247
TI  - The Pathway To Establishing HIV Latency Is Critical to How Latency Is Maintained
      and Reversed.
AB  - HIV infection requires lifelong antiretroviral therapy because of the persistence
      of latently infected CD4+ T cells. The induction of virus expression from
      latently infected cells occurs following T cell receptor (TCR) activation, but
      not all latently infected cells respond to TCR stimulation. We compared two
      models of latently infected cells using an enhanced green fluorescent protein
      (EGFP) reporter virus to infect CCL19-treated resting CD4+ (rCD4+) T cells
      (preactivation latency) or activated CD4+ T cells that returned to a resting
      state (postactivation latency). We isolated latently infected cells by sorting
      for EGFP-negative (EGFP-) cells after infection. These cells were cultured with
      antivirals and stimulated with anti-CD3/anti-CD28, mitogens, and latency
      reversing agents (LRAs) and cocultured with monocytes and anti-CD3. Spontaneous
      EGFP expression was more frequent in postactivation than in preactivation
      latency. Stimulation of latently infected cells with monocytes/anti-CD3 resulted
      in an increase in EGFP expression compared to that for unstimulated controls
      using the preactivation latency model but led to a reduction in EGFP expression
      in the postactivation latency model. The reduced EGFP expression was not
      associated with reductions in the levels of viral DNA or T cell proliferation but
      depended on direct contact between monocytes and T cells. Monocytes added to the
      postactivation latency model during the establishment of latency reduced
      spontaneous virus expression, suggesting that monocyte-T cell interactions at an
      early time point postinfection can maintain HIV latency. This direct comparison
      of pre- and postactivation latency suggests that effective strategies needed to
      reverse latency will depend on how latency is established.IMPORTANCE One strategy
      being evaluated to eliminate latently infected cells that persist in HIV-infected
      individuals on antiretroviral therapy (ART) is to activate HIV expression or
      production with the goal of inducing virus-mediated cytolysis or immune-mediated
      clearance of infected cells. The gold standard for the activation of latent virus
      is T cell receptor stimulation with anti-CD3/anti-CD28. However, this stimulus
      activates only a small proportion of latently infected cells. We show clear
      differences in the responses of latently infected cells to activating stimuli
      based on how latent infection is established, an observation that may potentially
      explain the persistence of noninduced intact proviruses in HIV-infected
      individuals on ART.

PMID- 29643249
TI  - Neutralizing Antibody Responses following Long-Term Vaccination with HIV-1 Env
      gp140 in Guinea Pigs.
AB  - A vaccination regimen capable of eliciting potent and broadly neutralizing
      antibodies (bNAbs) remains an unachieved goal of the HIV-1 vaccine field. Here we
      report the immunogenicity of longitudinal prime/boost vaccination regimens over a
      period of 200 weeks in guinea pigs with a panel of HIV-1 envelope (Env) gp140
      protein immunogens. We assessed vaccine regimens that included a monovalent clade
      C gp140 regimen (C97), a tetravalent regimen consisting of four clade C gp140s
      (4C), and a tetravalent regimen consisting of a clade A, B, C, and mosaic gp140
      (ABCM). We found that the 4C and ABCM prime/boost regimens were capable of
      eliciting a greater magnitude and breadth of binding antibodies targeting
      variable loop 2 (V2) over time, compared to the monovalent C97 only regimen. The
      longitudinal boosting regimen conducted over more than two years increased the
      magnitude of certain tier 1 NAbs, but did not increase the magnitude or breadth
      of heterologous tier 2 NAbs. These data suggest that additional immunogen design
      strategies are needed to induce broad, high titer tier 2 NAbs.IMPORTANCE The
      elicitation of potent, broadly neutralizing antibodies (bNAbs) remains an elusive
      goal for the HIV-1 vaccine field. In this study we explored the use of a long
      term vaccination regimen with differing immunogens to determine if we could
      elicit bNAbs in guinea pigs. We found that longitudinal boosting over more than
      two years increased tier 1 NAbs but did not increase the magnitude and breadth of
      tier 2 NAbs. These data suggest that additional immunogen designs and vaccination
      strategies will be necessary to induce broad tier 2 NAb responses.

PMID- 29643250
TI  - Neuronal subtype determines HSV-1 Latency-Associated-Transcript (LAT) promoter
      activity during latency.
AB  - Herpes simplex virus (HSV) latency in neurons remains poorly understood, and the
      heterogeneity of the sensory nervous system complicates mechanistic studies. In
      this study, we used primary culture of adult trigeminal ganglion (TG) mouse
      neurons in microfluidic devices, and an in vivo model, to examine the subtypes of
      sensory neurons involved in HSV latency. HSV-infected neurofilament heavy
      positive neurons (NefH+) were more likely to express Latency-Associated
      Transcripts (LATs) relative to infected neurofilament heavy-negative neurons
      (NefH-). This differential expression of the LAT promoter correlated with
      differences in HSV-1 early infection that manifested as differences in the
      efficiency with which HSV particles reached the cell body following infection at
      the distal axon. In vivo, we further identified a specific subset of NefH+
      neurons which co-expressed Calcitonin Gene Related Peptide alpha (NefH+ CGRP+) as
      the sensory neuron subpopulation with the highest LAT promoter activity following
      HSV-1 infection. Finally, an early-phase reactivation assay showed HSV-1
      reactivating in NefH+ CGRP+ neurons, although other sensory neuron subpopulations
      were also involved. Together, these results show that sensory neurons expressing
      neurofilaments exhibit enhanced LAT promoter activity. We hypothesize that
      reduced efficiency of HSV-1 invasion at an early phase of infection may promote
      efficient establishment of latency in NefH+ neurons due to initiation of the
      antiviral state preceding arrival of the virus at the neuronal cell body. While
      the outcome of HSV-1 infection of neurons is determined by a broad variety of
      factors in vivo, neuronal subtypes are likely to play differential roles in
      modulating the establishment of latent infection.Importance: Two pivotal
      properties of HSV-1 make it a successful pathogen. Firstly, it infects neurons
      which are immune-privileged. Secondly, it establishes latency in these neurons.
      Together, these properties allow HSV to persist for the lifetime of its host.
      Neurons are diverse and highly organized cells, with specific anatomical,
      physiological and molecular characteristics. Previous work has shown that
      establishment of latency by HSV-1 does not occur equally in all types of neurons.
      Our results show that the kinetics of HSV infection and levels of latency-related
      gene expression differ in certain types of neurons. The neuronal subtype infected
      by HSV is therefore a critical determinant of the outcome of infection and
      latency.

PMID- 29643248
TI  - A Single Amino Acid in the Polymerase Acidic Protein Determines the Pathogenicity
      of Influenza B Viruses.
AB  - Influenza B virus (IBV) is one of the human respiratory viruses and one of the
      targets of seasonal vaccination. However, the bifurcation of two antigenically
      distinct lineages of IBVs makes it difficult to arrange proper medical
      countermeasures. Moreover, compared with pathogenicity-related molecular markers
      known for influenza A virus, little has been known for IBVs. To understand
      pathogenicity caused by IBVs, we investigated the molecular determinants of IBV
      pathogenicity in animal models. After serial lung-to-lung passages of Victoria
      lineage B/Brisbane/60/2008 (Vc_BR60) and Yamagata lineage B/Wisconsin/01/2010
      (Ym_WI01) viruses in BALB/c mice, we identified the mouse-adapted Vc_BR60
      (maVc_BR60) and Ym_WI01 (maYm_WI01) viruses, respectively. To find a molecular
      clue(s) to the increased pathogenicity of maVc_BR60 and maYm_WI01, we determined
      their genetic sequences. Several amino acid mutations were identified in the PB2,
      PB1, PA, BM2, and/or NS1 protein-coding regions, and one concurrent lysine (K)-to
      arginine (R) mutation in PA residue 338 (PA K338R) was found in both maVc_BR60
      and maYm_WI01 viruses. When analyzed using viruses rescued through reverse
      genetics, it was shown that PA K338R alone could increase the pathogenicity of
      both IBVs in mice and viral replication in the respiratory tracts of ferrets. In
      a subsequent minireplicon assay, the effect of PA K338R was highlighted by the
      enhancement of viral polymerase complex activity of both Vc_BR60 and Ym_WI01
      viruses. These results suggest that the PA K338R mutation may be a molecular
      determinant of IBV pathogenicity via modulating the viral polymerase function of
      IBVs.IMPORTANCE To investigate molecular pathogenic determinants of IBVs, which
      are one of the targets of seasonal influenza vaccines, we adapted both Victoria
      and Yamagata lineage IBVs independently in mice. The recovered mouse-adapted
      viruses exhibited increased virulence, and of the various mutations identified
      from both mouse-adapted viruses, a concurrent amino acid mutation was found in
      the PA protein-coding region. When analyzed using viruses rescued through reverse
      genetics, the PA mutation alone appeared to contribute to viral pathogenicity in
      mice within the compatible genetic constellation between the IBV lineages and to
      the replication of IBVs in ferrets. Regarding the potential mechanism of
      increased viral pathogenicity, it was shown that the PA mutation could upregulate
      the viral polymerase complex activity of both IBV lineages. These results
      indicate that the PA mutation could be a newly defined molecular pathogenic
      determinant of IBVs that substantiates our understanding of the viral
      pathogenicity and public health risks of IBVs.

PMID- 29643251
TI  - Pharmacological Characterization of IW-1973, a Novel Soluble Guanylate Cyclase
      Stimulator with Extensive Tissue Distribution, Antihypertensive, Anti
      Inflammatory, and Antifibrotic Effects in Preclinical Models of Disease.
AB  - Soluble guanylate cyclase (sGC), a key signal-transduction enzyme, increases the
      conversion of guanosine-5'-triphosphate to cGMP upon binding of nitric oxide
      (NO). Endothelial dysfunction and/or reduced NO signaling have been implicated in
      cardiovascular disease pathogenesis and complications of diabetes and have been
      associated with other disease states and aging. Soluble guanylate cyclase (sGC)
      stimulators are small-molecule drugs that bind sGC and enhance NO-mediated cGMP
      signaling. The pharmacological characterization of IW-1973 [1,1,1,3,3,3
      hexafluoro-2-(((5-fluoro-2-(1-(2-fluorobenzyl)-5-(isoxazol-3-yl)-1H-pyrazol-3-yl)
      pyrimidin-4-yl)amino)methyl)propan-2-ol], a novel clinical-stage sGC stimulator
      under clinical investigation for treatment of heart failure with preserved
      ejection fraction and diabetic nephropathy, is described. In the presence of NO,
      IW-1973 stimulated sGC in a human purified enzyme assay and a HEK-293 whole cell
      assay. sGC stimulation by IW-1973 in cells was associated with increased
      phosphorylation of vasodilator-stimulated phosphoprotein. IW-1973, at doses of 1
      10 mg/kg, significantly lowered blood pressure in normotensive and spontaneously
      hypertensive rats. In a Dahl salt-sensitive hypertension model, IW-1973
      significantly reduced blood pressure, inflammatory cytokine levels, and renal
      disease markers, including proteinuria and renal fibrotic gene expression. The
      results were affirmed in mouse lipopolysaccharide-induced inflammation and rat
      unilateral ureteral obstruction renal fibrosis models. A quantitative whole-body
      autoradiography study of IW-1973 revealed extensive tissue distribution and
      pharmacokinetic studies showed a large volume of distribution and a profile
      consistent with predicted once-a-day dosing in humans. In summary, IW-1973 is a
      potent, orally available sGC stimulator that exhibits renoprotective, anti
      inflammatory, and antifibrotic effects in nonclinical models.

PMID- 29643253
TI  - In Vitro-In Vivo Extrapolation of OATP1B-Mediated Drug-Drug Interactions in
      Cynomolgus Monkey.
AB  - Hepatic organic anion-transporting polypeptides (OATP) 1B1 and 1B3 are clinically
      relevant transporters associated with significant drug-drug interactions (DDIs)
      and safety concerns. Given that OATP1Bs in cynomolgus monkey share >90% degree of
      gene and amino acid sequence homology with human orthologs, we evaluated the in
      vitro-in vivo translation of OATP1B-mediated DDI risk using this preclinical
      model. In vitro studies using plated cynomolgus monkey hepatocytes showed active
      uptake Km values of 2.0 and 3.9 uM for OATP1B probe substrates, pitavastatin and
      rosuvastatin, respectively. Rifampicin inhibited pitavastatin and rosuvastatin
      active uptake in monkey hepatocytes with IC50 values of 3.0 and 0.54 uM,
      respectively, following preincubation with the inhibitor. Intravenous
      pharmacokinetics of 2H4-pitavastatin and 2H6-rosuvastatin (0.2 mg/kg) and the
      oral pharmacokinetics of cold probes (2 mg/kg) were studied in cynomolgus monkeys
      (n = 4) without or with coadministration of single oral ascending doses of
      rifampicin (1, 3, 10, and 30 mg/kg). A rifampicin dose-dependent reduction in
      i.v. clearance of statins was observed. Additionally, oral pitavastatin and
      rosuvastatin plasma exposure increased up to 19- and 15-fold at the highest dose
      of rifampicin, respectively. Use of in vitro IC50 obtained following 1 hour
      preincubation with rifampicin (0.54 uM) predicted correctly the change in mean
      i.v. clearance and oral exposure of statins as a function of mean unbound maximum
      plasma concentration of rifampicin. This study demonstrates quantitative
      translation of in vitro OATP1B IC50 to predict DDIs using cynomolgus monkey as a
      preclinical model and provides further confidence in application of in vitro
      hepatocyte data for the prediction of clinical OATP1B-mediated DDIs.

PMID- 29643254
TI  - New Targets for Old Drugs: Cardiac Glycosides Inhibit Atrial-Specific K2P3.1
      (TASK-1) Channels.
AB  - Cardiac glycosides have been used in the treatment of arrhythmias for more than
      200 years. Two-pore-domain (K2P) potassium channels regulate cardiac action
      potential repolarization. Recently, K2P3.1 [tandem of P domains in a weak inward
      rectifying K+ channel (TWIK)-related acid-sensitive K+ channel (TASK)-1] has been
      implicated in atrial fibrillation pathophysiology and was suggested as an atrial
      selective antiarrhythmic drug target. We hypothesized that blockade of cardiac
      K2P channels contributes to the mechanism of action of digitoxin and digoxin. All
      functional human K2P channels were screened for interactions with cardiac
      glycosides. Human K2P channel subunits were expressed in Xenopus laevis oocytes,
      and voltage clamp electrophysiology was used to record K+ currents. Digitoxin
      significantly inhibited K2P3.1 and K2P16.1 channels. By contrast, digoxin
      displayed isolated inhibitory effects on K2P3.1. K2P3.1 outward currents were
      reduced by 80% (digitoxin, 1 Hz) and 78% (digoxin, 1 Hz). Digitoxin inhibited
      K2P3.1 currents with an IC50 value of 7.4 uM. Outward rectification properties of
      the channel were not affected. Mutagenesis studies revealed that amino acid
      residues located at the cytoplasmic site of the K2P3.1 channel pore form parts of
      a molecular binding site for cardiac glycosides. In conclusion, cardiac
      glycosides target human K2P channels. The antiarrhythmic significance of
      repolarizing atrial K2P3.1 current block by digoxin and digitoxin requires
      validation in translational and clinical studies.

PMID- 29643252
TI  - In Vitro Pharmacological Characterization and In Vivo Validation of LSN3172176 a
      Novel M1 Selective Muscarinic Receptor Agonist Tracer Molecule for Positron
      Emission Tomography.
AB  - In the search for improved symptomatic treatment options for neurodegenerative
      and neuropsychiatric diseases, muscarinic acetylcholine M1 receptors (M1 mAChRs)
      have received significant attention. Drug development efforts have identified a
      number of novel ligands, some of which have advanced to the clinic. However, a
      significant issue for progressing these therapeutics is the lack of robust,
      translatable, and validated biomarkers. One valuable approach to assessing target
      engagement is to use positron emission tomography (PET) tracers. In this study we
      describe the pharmacological characterization of a selective M1 agonist amenable
      for in vivo tracer studies. We used a novel direct binding assay to identify
      nonradiolabeled ligands, including LSN3172176, with the favorable characteristics
      required for a PET tracer. In vitro functional and radioligand binding
      experiments revealed that LSN3172176 was a potent partial agonist (EC50 2.4-7.0
      nM, Emax 43%-73%), displaying binding selectivity for M1 mAChRs (Kd = 1.5 nM)
      that was conserved across species (native tissue Kd = 1.02, 2.66, 8, and 1.03 at
      mouse, rat, monkey, and human, respectively). Overall selectivity of LSN3172176
      appeared to be a product of potency and stabilization of the high-affinity state
      of the M1 receptor, relative to other mAChR subtypes (M1 > M2, M4, M5 > M3). In
      vivo, use of wild-type and mAChR knockout mice further supported the M1
      preferring selectivity profile of LSN3172176 for the M1 receptor (78% reduction
      in cortical occupancy in M1 KO mice). These findings support the development of
      LSN3172176 as a potential PET tracer for assessment of M1 mAChR target engagement
      in the clinic and to further elucidate the function of M1 mAChRs in health and
      disease.

PMID- 29643255
TI  - Letter by Mojadidi et al Regarding Article, "Closure of Patent Foramen Ovale
      Versus Medical Therapy in Patients With Cryptogenic Stroke or Transient Ischemic
      Attack: Updated Systematic Review and Meta-Analysis".

PMID- 29643257
TI  - Pseudo-Occlusion of the Internal Carotid Artery Predicts Poor Outcome After
      Reperfusion Therapy.
AB  - BACKGROUND AND PURPOSE: This study aimed to evaluate the occurrence rate of the
      internal carotid artery pseudo-occlusion (ICA-PO) on 4-dimensional-computed
      tomography angiography and to investigate its relationship with clinical outcome
      after reperfusion therapy. METHODS: In this case-control study, we
      retrospectively reviewed our prospectively collected database for consecutive
      acute ischemic stroke patients who received reperfusion therapy between June 2009
      and February 2017. ICA-PO was defined when the arterial segment was not opacified
      on peak arterial phase yet was subsequently patent after artery peak phase on 4
      dimensional-computed tomography angiography. Poor outcome was defined as 3-month
      modified Rankin Scale of 4 to 6. Binary logistic regression was used to
      investigate the relationship of ICA-PO with poor outcome and the rate of
      reperfusion, respectively. RESULTS: A total of 143 patients with isolated middle
      cerebral artery occlusion were included and 30 (21.0%) had ICA-PO. Patients with
      ICA-PO were more likely to have poor outcome (80.0% versus 37.2%; P<0.001) and a
      lower rate of reperfusion (45.8% versus 69.0%; P=0.033) than those without.
      Binary logistic regression revealed that ICA-PO was independently associated with
      poor outcome (odds ratio, 7.957; 95% confidence interval, 1.655-34.869; P=0.009)
      and reperfusion at 24 hours (odds ratio, 0.150; 95% confidence interval, 0.045
      0.500; P=0.002) after adjustment. Among patients with no reperfusion, all ICA-PO
      patients obtained poor outcome, whereas only 45.2% non-PO patients underwent poor
      outcome (P=0.001). CONCLUSIONS: Four dimensional-computed tomography angiography
      is a useful noninvasive technique to identify ICA-PO. Patients with ICA-PO are
      prone to undergo poor outcome from reperfusion therapy, especially when
      reperfusion is not achieved.

PMID- 29643256
TI  - Critical Role of Flavin and Glutathione in Complex I-Mediated Bioenergetic
      Failure in Brain Ischemia/Reperfusion Injury.
AB  - BACKGROUND AND PURPOSE: Ischemic brain injury is characterized by 2 temporally
      distinct but interrelated phases: ischemia (primary energy failure) and
      reperfusion (secondary energy failure). Loss of cerebral blood flow leads to
      decreased oxygen levels and energy crisis in the ischemic area, initiating a
      sequence of pathophysiological events that after reoxygenation lead to
      ischemia/reperfusion (I/R) brain damage. Mitochondrial impairment and oxidative
      stress are known to be early events in I/R injury. However, the biochemical
      mechanisms of mitochondria damage in I/R are not completely understood. METHODS:
      We used a mouse model of transient focal cerebral ischemia to investigate acute
      I/R-induced changes of mitochondrial function, focusing on mechanisms of primary
      and secondary energy failure. RESULTS: Ischemia induced a reversible loss of
      flavin mononucleotide from mitochondrial complex I leading to a transient
      decrease in its enzymatic activity, which is rapidly reversed on reoxygenation.
      Reestablishing blood flow led to a reversible oxidative modification of
      mitochondrial complex I thiol residues and inhibition of the enzyme.
      Administration of glutathione-ethyl ester at the onset of reperfusion prevented
      the decline of complex I activity and was associated with smaller infarct size
      and improved neurological outcome, suggesting that decreased oxidation of complex
      I thiols during I/R-induced oxidative stress may contribute to the
      neuroprotective effect of glutathione ester. CONCLUSIONS: Our results unveil a
      key role of mitochondrial complex I in the development of I/R brain injury and
      provide the mechanistic basis for the well-established mitochondrial dysfunction
      caused by I/R. Targeting the functional integrity of complex I in the early phase
      of reperfusion may provide a novel therapeutic strategy to prevent tissue injury
      after stroke.

PMID- 29643258
TI  - Prevalence of Poststroke Neurocognitive Disorders Using National Institute of
      Neurological Disorders and Stroke-Canadian Stroke Network, VASCOG Criteria
      (Vascular Behavioral and Cognitive Disorders), and Optimized Criteria of
      Cognitive Deficit.
AB  - BACKGROUND AND PURPOSE: The prevalence of poststroke neurocognitive disorder
      (NCD) has yet to be accurately determined. The primary objective of the present
      study was to optimize operationalization of the criterion for NCD by using an
      external validity criterion. METHODS: The GRECOG-VASC cohort (Groupe de Reflexion
      pour l'Evaluation Cognitive Vasculaire) of 404 stroke patients with cerebral
      infarct (91.3%) or hemorrhage (18.7%) was assessed 6 months poststroke and 1003
      healthy controls, with the National Institute of Neurological Disorders and
      Stroke-Canadian Stroke Network standardized battery. Three dimensions of the
      criterion for cognitive impairment were systematically examined by using the
      false-positive rate as an external validity criterion. Diagnosis of mild and
      major NCD was based on the VASCOG criteria (Vascular Behavioral and Cognitive
      Disorders). The mechanisms of functional decline were systematically assessed.
      RESULTS: The optimal criterion for cognitive impairment was the shortened summary
      score (ie, averaged performance for action speed, executive functions, and
      language) because it was associated with the highest (P=0.0001) corrected true
      positive rate (43.5%) and a false-positive rate <=5%. Using this criterion, the
      mean (95% confidence interval) prevalence of poststroke NCD was 49.5% (44.6
      54.4), most of which corresponded to mild NCD (39.1%; 95% confidence interval,
      34.4-43.9) rather than dementia (10.4%; 95% confidence interval, 7.4-13.4).
      CONCLUSIONS: This study is the first to have optimized the operationalization of
      the criterion for poststroke cognitive impairment. It documented the prevalence
      of poststroke NCD in the GRECOG-VASC cohort and showed that mild cognitive
      impairment accounts for 80% of the affected patients. Finally, the method
      developed in the present study offers a means of harmonizing the diagnosis of
      NCD. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique
      identifier: NCT01339195.

PMID- 29643259
TI  - Cerebrovascular Accidents During Mechanical Circulatory Support: New Predictors
      of Ischemic and Hemorrhagic Strokes and Outcome.
AB  - BACKGROUND AND PURPOSE: Left ventricular assist devices (LVADs) have emerged as
      an effective treatment for patients with advanced heart failure refractory to
      medical therapy. Post-LVAD strokes are an important cause of morbidity and
      reduced quality of life. Data on risks that distinguish between ischemic and
      hemorrhagic post-LVAD strokes are limited. The aim of this study was to determine
      the incidence of post-LVAD ischemic and hemorrhagic strokes, their association
      with stroke risk factors, and their effect on mortality. METHODS: Data are
      collected prospectively on all patients with LVADs implanted at Brigham and
      Women's Hospital. We added retrospectively collected clinical data for these
      analyses. RESULTS: From 2007 to 2016, 183 patients (median age, 57; 80% male)
      underwent implantation of HeartMate II LVAD as a bridge to transplant (52%),
      destination therapy (39%), or bridge to transplant candidacy (8%). A total of 48
      strokes occurred in 39 patients (21%): 28 acute ischemic strokes in 24 patients
      (13%) and 20 intracerebral hemorrhages in 19 patients (10.3%). First events
      occurred at a median of 238 days from implantation (interquartile range, 93-515)
      among those who developed post-LVAD stroke. All but 9 patients (4.9%) were on
      warfarin (goal international normalized ratio, 2-3.5) and all received aspirin
      (81-325 mg). Patients with chronic obstructive pulmonary disease were more likely
      to have an ischemic stroke (odds ratio, 2.96; 95% confidence interval, 1.14
      7.70). Dialysis-dependent patients showed a trend toward a higher risk of
      hemorrhagic stroke (odds ratio, 6.31; 95% confidence interval, 0.99-40.47).
      Hemorrhagic stroke was associated with higher mortality (odds ratio, 3.92; 95%
      confidence interval, 1.34-11.45) than ischemic stroke (odds ratio, 3.17; 95%
      confidence interval, 1.13-8.85). CONCLUSIONS: Stroke is a major cause of
      morbidity and mortality in patients on LVAD support. Chronic obstructive
      pulmonary disease increases the risk of ischemic stroke, whereas dialysis may
      increase the risk of hemorrhagic stroke. Although any stroke increases mortality,
      post-LVAD hemorrhagic stroke was associated with higher mortality compared with
      ischemic stroke.

PMID- 29643260
TI  - Letter by Doshi et al Regarding Article, "Closure of Patent Foramen Ovale Versus
      Medical Therapy in Patients With Cryptogenic Stroke or Transient Ischemic Attack:
      Updated Systematic Review and Meta-Analysis".

PMID- 29643262
TI  - Response by Ntaios et al to Letter Regarding Article, "Closure of Patent Foramen
      Ovale Versus Medical Therapy in Patients With Cryptogenic Stroke or Transient
      Ischemic Attack: Updated Systematic Review and Meta-Analysis".

PMID- 29643261
TI  - Primary Results of the Multicenter ARISE II Study (Analysis of Revascularization
      in Ischemic Stroke With EmboTrap).
AB  - BACKGROUND AND PURPOSE: EmboTrap is a novel stent retriever designed to achieve
      rapid and substantial flow restoration in acute ischemic stroke secondary to
      large-vessel occlusions. Here, we evaluated EmboTrap's safety and efficacy
      compared with established stent retrievers. METHODS: ARISE II (Analysis of
      Revascularization in Ischemic Stroke With EmboTrap) was a single-arm,
      prospective, multicenter study, comparing the EmboTrap device to a composite
      performance goal criterion derived using a Bayesian meta-analysis from the
      pivotal SWIFT (Solitaire device) and TREVO 2 (Trevo device) trials. Patients at
      11 US and 8 European sites were eligible for inclusion if they had large-vessel
      occlusions and moderate-to-severe neurological deficits within 8 hours of symptom
      onset. The primary efficacy end point was achievement of modified Thrombolysis in
      Cerebral Ischemia (mTICI) reperfusion scores of >=2b within 3 EmboTrap passes as
      adjudicated by the core laboratory. The primary safety end point was a composite
      of symptomatic intracerebral hemorrhage and serious adverse device effects.
      Secondary end points included functional independence (modified Rankin Scale, 0
      2) and all-cause mortality at 90 days. RESULTS: Between October 2015 and February
      2017, 227 patients were enrolled and treated with the EmboTrap device. The
      primary efficacy end point (mTICI >=2b within 3 passes) was achieved in 80.2%
      (95% confidence interval, 74%-85% versus 56% performance goal criterion; P value,
      <0.0001), and mTICI 2c/3 was 65%. After all interventions, mTICI 2c/3 was
      achieved in 76%, and mTICI >=2b was 92.5%. The rate of first pass (mTICI >=2b
      following a single pass) was 51.5%. The primary safety end point composite rate
      of symptomatic intracerebral hemorrhage or serious adverse device effects was
      5.3%. Functional independence and all-cause mortality at 90 days were 67% and 9%,
      respectively. CONCLUSIONS: The EmboTrap stent-retriever mechanical thrombectomy
      device demonstrated high rates of substantial reperfusion and functional
      independence in patients with acute ischemic stroke secondary to large-vessel
      occlusions. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov.
      Unique identifier: NCT02488915.

PMID- 29643263
TI  - Health State Utilities for Patient's Current Health from Bipolar Type I Disorder.
AB  - BACKGROUND: Bipolar Type I Disorder (BID) is a disabling mental disorder among
      young adults that places enormous psychological, social, and economic burdens on
      patients, their families, and health care systems and decreases quality of life
      (QOL). Few studies have investigated the quality-adjusted life-years (QALY),
      health state preferences, and utilities in patients with BID. AIM OF STUDY: The
      aim of this study was to elicit health state utilities for current health among a
      sample of individuals with BID irrespective of their clinical conditions at the
      time of evaluation. METHODS: One hundred individuals with BID were consecutively
      enrolled in this cross-sectional study. Preferences were elicited from patients
      with visual analogous scale (VAS) and time trade-off (TTO). To assess quality of
      life, the Farsi version of the World Health Organization's QOL Instrument-Short
      Version (WHOQOL-BREF) was used. In addition, health state was assessed with the
      Short Form-36 (SF-36) health survey, and then a specially- derived reduced
      version of the SF-36 (the 'SF-6D') was calculated as an alternative to existing
      preference-based measures of health for conducting economic evaluation of various
      interventions. Moreover, several clinical measures were administered to
      participants. RESULTS: The mean (S.D.) VAS, TTO, and SF-6D utility scores were
      0.59 (0.21), 0.44 (0.33), and 0.61 (0.11), respectively. There were significant
      associations of most selected clinical characteristics with VAS and TTO scores.
      Additionally, there were strong correlations between all domains of WHOQOL-BREF
      and VAS scores as well as moderate to strong correlations with TTO scores.
      Furthermore, there were strong correlations between all scales of SF-36 scores
      and VAS scores as well as moderate to strong correlations between the scales of
      SF-36 scores and TTO scores. DISCUSSION: The current study showed that even
      unstable patients could evaluate their own health states. Furthermore, the
      present study showed substantial decrements in health-related life preferences
      among persons with BID. Additionally, the patients with most recent depressive or
      mixed episodes reported lower VAS scores than those with most recent manic
      episodes. LIMITATIONS: This study was performed on a group of patients with BID
      in a referral psychiatric center. This sample can potentially make a selection
      bias. Furthermore, this study was cross-sectional. IMPLICATIONS FOR HEALTH CARE
      PROVISION AND USE: Generally, clinical features could explain more than half of
      the variances in VAS utility scores. Among all clinical features, severity of
      symptoms and duration of disease were among the main factors significantly
      associated with the utility decreases. IMPLICATION FOR HEALTH POLICIES: The
      present study data provide health state preferences useful for cost-utility and
      outcome-modeling studies as well as health policy and decision-making. Also, the
      evaluations were partially affected by severity of symptoms. Therefore, utilities
      obtained in this study can be utilized to develop QALY and provide utility values
      that can be used in economic models for cost-utility studies. IMPLICATIONS FOR
      FURTHER RESEARCH: The comparison of the utility in a group of patients in
      different mood episodes and in their controlled periods and calculating the
      proportion of each episode to total duration of disease and to the patient's life
      span in future investigations may add crucial information to the present
      knowledge. The evaluation of biological and non-biological therapies by measuring
      utility and health value as health output indicators is strongly suggested.

PMID- 29643264
TI  - How does Economic Recession Affect Substance Use? A Reality Check with Clients of
      Drug Treatment Centres.
AB  - INTRODUCTION: The relationship between economic downturns and substance use has
      been studied in numerous economic crises occurring worldwide, but the precise
      relationship between the two remains unclear. AIMS: The aim of the present study
      was to undertake a survey on behaviour and perspectives related to the latest
      European economic crisis among illegal drug users attending substance treatment
      services. DESIGN AND METHODS: We conducted a questionnaire-based survey in drug
      dependence treatment settings, in three geographically different jurisdictions
      (England, Catalonia and Poland), including 180 drug users. RESULTS: Most of the
      participants of the survey (58.3%) reported an increase in drug use during the
      crisis, compared with only 25.6% of the sample who reported a decrease in drug
      use. The main reason given for increasing drug use was greater amount of free
      time available. Other important reasons were greater substance availability
      during this period, more stress at work and seeking comfort in response to the
      loss of a stable source of income, social status and/or family. Those who
      reported cutting down on the amount of drug use during the economic recession,
      reported economic difficulties as the main reason. Other important factors were
      family and friends' economic problems and the fear of losing their job. Illegal
      drug use reduction was compensated by increased smoking in 46.3% of the patients,
      and increased alcohol use in 39.4%. DISCUSSION AND CONCLUSIONS: While this result
      has potential interest for those developing policies and interventions to reduce
      drug-related harm, longitudinal studies and future research involving a broader
      population of drug-users (including those not in treatment) could shed further
      light on these behavioural mechanisms linking changes in drug use with economic
      recessions.

PMID- 29643265
TI  - Thirty-day Readmission Rates and Associated Factors: A Multilevel Analysis of
      Practice Variations in French Public Psychiatry.
AB  - BACKGROUND: Inpatient psychiatric readmissions are often used as an indicator of
      the quality of care and their reduction is in line with international
      recommendations for mental health care. Research on variations in inpatient
      readmission rates among mental health care providers is therefore of key
      importance as these variations can impact equity, quality and efficiency of care
      when they do not result from differences in patients' needs. AIMS OF THE STUDY:
      Our objectives were first to describe variations in inpatient readmission rates
      between public mental health care providers in France on a nationwide scale, and
      second, to identify their association with patient, health care providers and
      environment characteristics. METHODS: We carried out a study for the year 2012
      using data from ten administrative national databases. 30-day readmissions in
      inpatient care were identified in the French national psychiatric discharge
      database. Variations were described numerically and graphically between French
      psychiatric sectors and factors associated with these variations were identified
      by carrying out a multi-level logistic regression accounting for the hierarchical
      structure of the data. RESULTS: Significant practice variations in 30-day
      inpatient readmission rates were observed with a coefficient of variation above
      50%. While a majority of those variations was related to differences within
      sectors, individual patient characteristics explained a lower part of the
      variations resulting from differences between sectors than the characteristics of
      sectors and of their environment. In particular, an increase in the mortality
      rate and in the acute admission rate for somatic disorders in sectors' catchment
      area was associated with a decrease in the probability of 30-day readmission.
      Similarly, an increase in the number of psychiatric inpatient beds in private for
      profit hospitals per 1,000 inhabitants in sectors' catchment area was associated
      with a decrease in this probability, which also varied with overall sectors' case
      mix characteristics and with the level of urbanisation of the area. DISCUSSION:
      The extent of the variations and the factors associated with it question the
      adequacy of care and suggest that some of them may be unwarranted. Our findings
      should however be interpreted in consideration of several limits inherent to data
      quality and availability as we relied on information from administrative
      databases. While we considered a wide range of factors potentially associated
      with variations in 30-day readmissions, our model indeed only explained a limited
      part of the variations resulting from differences between sectors. IMPLICATIONS
      FOR HEALTH POLICIES: Our findings underscored that practice variations in
      psychiatry are a reality that merits the full attention of decision makers as
      they can impact the quality, equity and efficiency of care. A specific data
      system should be established to monitor practice variations in routine to promote
      transparency and accountability. IMPLICATIONS FOR FURTHER RESEARCH: Few
      associations were found between variations in 30-day inpatient readmissions and
      the supply of care. The routine collection of detailed organizational
      characteristics of health care providers at a national level should be supported
      to facilitate additional research work, both in France and in other contexts.

PMID- 29643266
TI  - Changes in the Utilization of Mental Health Care Services and Mental Health at
      the Onset of Medicare.
AB  - BACKGROUND: The onset of Medicare eligibility at age 65 in the U.S. is
      accompanied by significant changes in health insurance coverage rates. This
      presents a unique opportunity to study the interaction among health insurance,
      health care utilization, and health outcomes. AIMS: This study examines if
      changes in mental health outcomes accompany the changes in health insurance
      coverage rates at age 65. METHODS: 2006-2013 data from the Sample Adult and
      Person File components of the National Health Insurance Survey are used to
      explore the link between the onset of Medicare and the utilization of mental
      health care services and mental health. A regression discontinuity design is
      employed to test for changes in perceived financial barriers to mental health
      care, visits with mental health professionals, and self-reported mental health.
      In addition to identifying the overall effect, analysis is also conducted on
      samples that are stratified by level of education to test for heterogeneous
      treatment effects across socioeconomic groups. RESULTS: The coverage changes that
      occur at age 65 are associated with a substantial decline in self-reported
      financial barriers to receiving mental health care. This effect is greatest among
      individuals from lower socioeconomic backgrounds. Despite the decline in the
      percentage of adults claiming they did not obtain mental health care services
      because of prohibitive costs, no significant changes in mental health visits or
      self-reported mental health are identified. The implementation of lower cost
      sharing requirements for outpatient mental health care through the Medicare
      Patients and Providers Act of 2008 (MIPPA) has had no statistically significant
      effect on mental health visits at the age 65 cutoff for Medicare eligibility.
      DISCUSSION: There is no estimated change in mental health visits, yet prohibitive
      costs of mental health care decline, especially among individuals from lower
      socioeconomic groups. These findings may be the result of newly eligible Medicare
      enrollees either increasing their utilization of mental health visits on the
      intensive margin, obtaining alternative sources of treatment for mental illness,
      or facing other barriers to care that are unrelated to costs. Additionally,
      estimates pertaining to mental health visits are imprecise, and large changes
      relative to age 64 means cannot be ruled out. IMPLICATIONS FOR HEALTH CARE
      PROVISION AND USE: There is no evidence that gaining health insurance coverage at
      age 65 results in increased visits with mental health professionals on the
      extensive margin. IMPLICATIONS FOR HEALTH POLICY: For the previously uninsured
      and under-insured, the onset of Medicare coverage at age 65 results in a
      reduction in cost-sharing requirements for mental health care. These reductions
      have no clear effect on overall mental health visit rates. Although the 2010
      implementation of MIPPA has gradually lowered cost-sharing requirements for
      outpatient mental health care, these changes have not affected mental health
      visits at age 65. IMPLICATIONS FOR FURTHER RESEARCH: Future research that
      evaluates whether additional factors, such as residing in a mental health
      shortage area, can explain the imprecise estimate on mental health visits would
      be useful. Additionally, future studies that examine the interaction between
      private insurance and Medicare coverage would better explain the dynamic changes
      that occur at age 65, and how shifting coverage patterns interact with mental
      health care utilization rates.

PMID- 29643267
TI  - Measurement of breath acetone in patients referred for an oral glucose tolerance
      test.
AB  - Breath acetone concentrations were measured in 141 subjects (aged 19-91 years,
      mean = 59.11 years, standard deviation = 12.99 years), male and female,
      undergoing an oral glucose tolerance test (OGTT), having been referred to clinic
      on suspicion of type 2 diabetes. Breath samples were measured using an ion
      molecule-reaction mass spectrometer, at the commencement of the OGTT, and after 1
      and 2 h. Subjects were asked to observe the normal routine before and during the
      OGTT, which includes an overnight fast and ingestion of 75 g glucose at the
      beginning of the routine. Several groups of diagnosis were identified: type 2
      diabetes mellitus positive (T2DM), n = 22; impaired glucose intolerance (IGT), n
      = 33; impaired fasting glucose, n = 14; and reactive hypoglycaemia, n = 5. The
      subjects with no diagnosis (i.e. normoglycaemia) were used as a control group, n
      = 67. Distributions of breath acetone are presented for the different groups.
      There was no evidence of a direct relationship between blood glucose (BG) and
      acetone measurements at any time during the study (0 h: p = 0.4482; 1 h: p =
      0.6854; and 2 h: p = 0.1858). Nor were there significant differences between the
      measurements of breath acetone for the control group and the T2DM group (0 h: p =
      0.1759; 1 h: p = 0.4521; and 2 h: p = 0.7343). However, the ratio of breath
      acetone at 1 h to the initial breath acetone was found to be significantly
      different for the T2DM group compared to both the control and IGT groups (p =
      0.0189 and 0.011, respectively). The T2DM group was also found to be different in
      terms of ratio of breath acetone after 1 h to that at 2 h during the OGTT. And
      was distinctive in that it showed a significant dependence upon the level of BG
      at 2 h (p = 0.0146). We conclude that single measurements of the concentrations
      of breath acetone cannot be used as a potential screening diagnostic for T2DM
      diabetes in this cohort, but monitoring the evolution of breath acetone could
      open a non-invasive window to aid in the diagnosis of metabolic conditions.

PMID- 29643268
TI  - Proposed cut-off value of CA19-9 for detecting pancreatic cancer in patients with
      diabetes: a case-control study.
AB  - Pancreatic cancer is a highly lethal malignancy. CA19-9 is a well-known marker
      for diagnosis of pancreatic cancer, but the serum CA19-9 level is reported to be
      elevated in patients with poorly controlled diabetes. This study evaluated the
      sensitivity, specificity, and cut-off value of serum CA19-9 for detection of
      pancreatic cancer in patients with diabetes. A case-control study of 236 patients
      was performed. The case group was selected from diabetic patients with pancreatic
      cancer, while one control was selected for each case from among diabetic patients
      without pancreatic cancer during the same period. The case group (n = 118) and
      the control group (n = 118) were matched for age, sex, and pancreatic cancer risk
      factors. Receiver operating characteristic (ROC) curves were plotted to determine
      the serum CA19-9 level that predicted pancreatic cancer. Then the sensitivity and
      specificity of CA19-9 were calculated for the threshold value. There were no
      significant differences of age, sex, BMI, smoking, alcohol intake, and HbA1c
      between the case and control groups. According to ROC analysis, a serum CA19-9
      level of 75 U/mL had the maximum sensitivity and specificity for separating
      diabetic patients with or without pancreatic cancer. Using this cut-off value,
      the sensitivity and specificity of CA19-9 for pancreatic cancer was 69.5% and
      98.2%, respectively, while the area under the ROC curve was 0.875 [95%CI: 0.826
      0.924]. We propose that a serum CA19-9 level of 75 U/mL should be used as the cut
      off value when screening patients with diabetes for pancreatic cancer.

PMID- 29643269
TI  - Signature of positive selection in mitochondrial DNA in Cetartiodactyla.
AB  - Acceleration of the amino acid substitution rate is a good indicator of positive
      selection in adaptive evolutionary changes of functional genes. Genomic
      information about mammals has become readily available in recent years, as many
      researchers have attempted to clarify the adaptive evolution of mammals by
      examining evolutionary rate change based on multiple loci. The order
      Cetartiodactyla (Artiodactyla and Cetacea) is one of the most diverse orders of
      mammals. Species in this order are found throughout all continents and seas,
      except Antarctica, and they exhibit wide variation in morphology and habitat.
      Here, we focused on the metabolism-related genes of mitochondrial DNA (mtDNA) in
      species of the order Cetartiodactyla using 191 mtDNA sequences available in
      databases. Based on comparisons of the dN/dS ratio (omega) in 12 protein-coding
      genes, ATP8 was shown to have a higher omega value (omega = 0.247) throughout
      Cetartiodactyla than the other 11 genes (omega < 0.05). In a branch-site analysis
      of ATP8 sequences, a markedly higher omega value of 0.801 was observed in the
      ancestral lineage of the clade of Cetacea, which is indicative of adaptive
      evolution. Through efforts to detect positively selected amino acids, codon
      positions 52 and 54 of ATP8 were shown to have experienced positive selective
      pressure during the course of evolution; multiple substitutions have occurred at
      these sites throughout the cetacean lineage. At position 52, glutamic acid was
      replaced with asparagine, and, at position 54, lysine was replaced with non
      charged amino acids. These sites are conserved in most Artiodactyla. These
      results imply that the ancestor of cetaceans underwent accelerated amino acid
      changes in ATP8 and replacements at codons 52 and 54, which adjusted metabolism
      to adapt to the marine environment.

PMID- 29643271
TI  - Japan Diet Intake Changes Serum Phospholipid Fatty Acid Compositions in Middle
      Aged Men: A Pilot Study.
AB  - AIM: The Japan Diet nutritional education program effects on serum fatty acid
      compositions for prevention of atherosclerotic cardiovascular disease in middle
      aged men brought up in the westernized dietary environment of modern Japan were
      examined. METHODS: Thirty-three men, 30-49 years of age, attended a nutrition
      education class and were recommended to consume Japan Diet volumes (more fish,
      soybeans and soy products, vegetables, seaweed, konjak, mushrooms, and unrefined
      cereals and less animal fat, meat and poultry with fat, sweets, desserts and
      snacks, and alcoholic drinks) for 6 weeks. Three-day weighted dietary records
      were kept, and fatty acid intakes were calculated. Serum phospholipid fatty acid
      compositions were examined. RESULTS: During the 6 weeks, fish, soy, and seaweed
      and/or mushrooms and/or konjak were consumed 1.0, 1.1, and 1.0 times daily on
      average, whereas daily fatty meat and poultry and sweet consumptions were 0.3 and
      0.3, respectively. These changes were attributed to increased intake of n-3
      polyunsaturated fatty acids (PUFAs) such as C20:5(n-3), C22:6(n-3), C18:4(n-3),
      and C20:4(n-3) and decreased intakes of all saturated fatty acids and unsaturated
      fatty acids such as C18:1 and C18:2(n-6). As to the phospholipid fatty acid
      composition, C18:0 decreased, whereas C15:0, C17:0, and C20:0 increased. Marked
      increases in C20:5(n-3) and C22:6(n-3) raised total n-3 PUFA from 10.30% to
      13.20% along with n-6 PUFA decreasing from 33.92% to 31.16%. Despite decreases in
      C20:4(n-6) and C20:3(n-6), the C20:4(n-6)/C20:3(n-6) ratio used as an estimate of
      delta-5 desaturase activities increased and correlated positively with fish
      intake at completion of the intervention. CONCLUSIONS: The Japan Diet is
      effective for changing the fatty acids to an anti-atherosclerotic profile.The
      clinical trial registration number: UMIN000020639.

PMID- 29643270
TI  - Comparison of personal air benzene and urine t,t-muconic acid as a benzene
      exposure surrogate during turnaround maintenance in petrochemical plants.
AB  - Previous studies have shown that biomarkers of chemicals with long half-lives may
      be better surrogates of exposure for epidemiological analyses, leading to less
      attenuation of the exposure-disease association, than personal air samples.
      However, chemicals with short half-lives have shown inconsistent results. In the
      present study, we compared pairs of personal air benzene and its short-half-life
      urinary metabolite trans,trans-muconic acid (t,t-MA), and predicted attenuation
      bias of theoretical exposure-disease association. Total 669 pairs of personal air
      benzene and urine t,t-MA samples were taken from 474 male workers during
      turnaround maintenance operations held in seven petrochemical plants. Maintenance
      jobs were classified into 13 groups. Variance components were calculated for
      personal air benzene and urine t,t-MA separately to estimate the attenuation of
      the theoretical exposure-disease association. Personal air benzene and urine t,t
      MA showed similar attenuation of the theoretical exposure-disease association.
      Analyses for repeated measurements showed similar results, while in analyses for
      values above the limits of detection (LODs), urine t,t-MA showed less attenuation
      of the theoretical exposure-disease association than personal air benzene. Our
      findings suggest that there may be no significant difference in attenuation bias
      when personal air benzene or urine t,t-MA is used as a surrogate for benzene
      exposure.

PMID- 29643272
TI  - Development of completely dispersed cellulose nanofibers.
AB  - Plant cellulose fibers of width and length ~0.03 mm and ~3 mm, respectively, can
      be completely converted to individual cellulose nanofibers of width and length ~3
      nm and ~1 um, respectively, by 2,2,6,6-tetramethylpiperidine-1-oxyl radical
      (TEMPO)-mediated oxidation under aqueous conditions and subsequent gentle
      mechanical disintegration of the oxidized cellulose in water. The obtained TEMPO
      oxidized cellulose nanofibers (TOCNs) are new bio-based, crystalline
      nanomaterials with applications in the high-tech and commodity product
      industries. Sodium carboxylate groups, which are densely, regularly, and position
      selectively present on the crystalline TOCN surfaces, can be efficiently ion
      exchanged with other metal and alkylammonium carboxylate groups in water to
      control the biodegradable/stable and hydrophilic/hydrophobic properties of the
      TOCNs. TOCNs are therefore promising nanomaterials that can be prepared from the
      abundant wood biomass resources present in Japan. Increased production and use of
      TOCNs would stimulate a new material stream from forestry to industries, helping
      to establish a sustainable society based on wood biomass resources.

PMID- 29643274
TI  - Hidden Peptides Encoded by Putative Noncoding RNAs.
AB  - Although the definition of a noncoding RNA (ncRNA) is an RNA molecule that does
      not encode a protein, recent evidence has revealed that some ncRNAs are indeed
      translated to give rise to small polypeptides (usually containing fewer than 100
      amino acids). Despite their small size, however, these peptides are often
      biologically relevant in that they are required for a variety of cellular
      processes. In this review, we summarize the production and functions of peptides
      that have been recently identified as translation products of putative ncRNAs.Key
      words: long noncoding RNA (lncRNA), circular RNA (circRNA), primary miRNA (pri
      miRNA), translation, peptide.

PMID- 29643275
TI  - Hypomethylation of the Interferon gamma Gene as a Potential Risk Factor for
      Essential Hypertension: A Case-Control Study.
AB  - Essential hypertension (EH) is a multifactorial disease. Interferon-gamma (IFN
      gamma) plays an important role in the onset of EH through cytokine-mediated
      systemic inflammatory responses. We aimed to determine whether the methylation
      status of the IFN-gamma gene (IFNG) promoter is involved in the pathogenesis of
      EH. Six copies of CpG dinucleotides are distributed between 3,203 bp and 3,121 bp
      upstream from the transcription initiation site of IFNG, termed CpG1 to CpG6 in
      the 5'-to-3' direction. We recruited 96 patients with EH and 96 sex- and age
      matched healthy subjects as controls. Using bisulfate pyrosequencing datasets, we
      analyzed the methylation status of the six CpG sites and thus found that CpG5 was
      consistently methylated in all of the 96 EH patients and 96 control subjects.
      Among the remaining five CpG sites, there was no significant difference in the
      methylation levels of CpG4 and CpG6 between the two groups. By contrast, CpG1 (P
      = 0.003) and CpG3 (P = 5.87 * 10-7) were highly methylated among the EH subjects
      compared with the controls, whereas CpG2 (P = 1.24 * 10-12) was significantly
      less methylated in among EH subjects. The methylation levels of CpG2 were still
      lower after adjustment with logistic regression (adjusted P = 0.032). The CpG2
      methylation level was an effective marker of EH (area under curve = 0.384; P =
      1.40 * 10-15). The present study shows that hypomethylation of the IFNG promoter
      is significantly related to the risk of EH, providing new insights into the
      pathogenesis of EH.

PMID- 29643273
TI  - MPF-based meiotic cell cycle control: Half a century of lessons from starfish
      oocytes.
AB  - In metazoans that undergo sexual reproduction, genomic inheritance is ensured by
      two distinct types of cell cycle, mitosis and meiosis. Mitosis maintains the
      genomic ploidy in somatic cells reproducing within a generation, whereas meiosis
      reduces by half the ploidy in germ cells to prepare for successive generations.
      The meiotic cell cycle is believed to be a derived form of the mitotic cell
      cycle; however, the molecular mechanisms underlying both of these processes
      remain elusive. My laboratory has long studied the meiotic cell cycle in starfish
      oocytes, particularly the control of meiotic M-phase by maturation- or M phase
      promoting factor (MPF) and the kinase cyclin B-associated Cdk1 (cyclin B-Cdk1).
      Using this system, we have unraveled the molecular principles conserved in
      metazoans that modify M-phase progression from the mitotic type to the meiotic
      type needed to produce a haploid genome. Furthermore, we have solved a long
      standing enigma concerning the molecular identity of MPF, a universal inducer of
      M-phase both in mitosis and meiosis of eukaryotic cells.

PMID- 29643276
TI  - Expression of Placenta Growth Factor Is Associated with Unfavorable Prognosis of
      Advanced-Stage Serous Ovarian Cancer.
AB  - Ovarian cancer is the fourth leading cause of cancer death in women and the most
      fatal gynecologic malignancy. Placenta growth factor (PGF), a member of the
      vascular endothelial growth factor, plays an important role in angiogenesis. The
      overexpression of PGF was observed in several types of cancers, but the clinical
      significance of PGF in epithelial ovarian cancer (EOC) is still unknown. To
      explore the prognostic value of PGF among patients with serous EOC, we analyzed
      the expression of PGF in 89 EOC specimens by immunohistochemistry. The scoring
      system of immunohistochemistry was based on the staining intensity and the
      percentage of PGF-positive cells in each EOC tissue. According to the
      immunohistochemical score, 34 patients with score >= 6 were defined as high PGF
      expression, and other 55 patients were the group with low PGF expression. The
      prognostic significance of PGF expression was analyzed. EOC patients with higher
      IHC scores of PGF expression are significantly associated with positive lymphatic
      invasion and poorer response to chemotherapy. Patients with higher IHC scores of
      PGF expression had poorer response to chemotherapy and lower overall survival
      rate. Additionally, the positive lymph node metastasis, advanced TNM stage, and
      poorer response to chemotherapy were all remarkably correlated to poorer
      prognosis. In conclusion, patients with higher PGF in EOC tissues were more
      predisposed to positive lymphatic invasion, poorer response to chemotherapy and
      unfavorable prognosis of patients with serous EOC. We propose that PGF expression
      may be predictive of chemoresistance and poor prognosis of serous EOC.

PMID- 29643277
TI  - The Characteristics of Coaches that Verbally or Physically Abuse Young Athletes.
AB  - Verbal or physical abuse from coaches has a negative impact on young athletes. To
      prevent abuse against young athletes, it is important to know the characteristics
      of abusive coaches. This study aimed to elucidate the characteristics of coaches
      who commit verbal or physical abuse in youth sports teams. A cross-sectional
      study was conducted with coaches of youth sport teams in Miyagi prefecture, Japan
      (n = 1,283), using a self-reported questionnaire (response rate was 24.0%).
      Multivariate logistic regression models were used for analyses. The prevalence of
      verbal and physical abuse towards young athletes was 64.7% (n = 830) and 6.2% (n
      = 79), respectively. Verbal abuse was significantly associated with lower
      educational attainment (odds ratio (OR): 1.32, 95% confidence interval (95% CI):
      1.03-1.69), experiences of verbal abuse by own coaches (OR: 1.85, 95% CI: 1.37
      2.50), acceptability for verbal or physical abuse (OR: 2.53, 95% CI: 1.82-3.52),
      and dissatisfaction with athletes' attitude (OR: 1.62, 95% CI: 1.26-2.07).
      Physical abuse was significantly associated with experiences of physical abuse by
      respondents' coaches (OR: 2.71, 95% CI: 1.50-4.92), acceptability for verbal or
      physical abuse (OR: 3.89, 95% CI: 2.39-6.33), and longer experience of coaching
      in years (OR: 2.45, 95% CI: 1.20-4.98). The results of this study show that
      coaches who commit verbal or physical abuse had typically experienced abuse from
      their former coaches, and adopted a similar style. Breaking the negative cycle of
      verbal and physical abuse is necessary to eliminate the abuse of young athletes.

PMID- 29643278
TI  - Absolute Myocardial Blood Flow After Elective Percutaneous Coronary Intervention
      Evaluated on Phase-Contrast Cine Cardiovascular Magnetic Resonance Imaging.
AB  - BACKGROUND: Few studies have documented changes in myocardial blood flow (MBF)
      after percutaneous coronary intervention (PCI). Phase-contrast cine
      cardiovascular MRI (PC-CCMR) of the coronary sinus (CS) is a promising approach
      to quantify MBF. The aim of this study was to quantify CS flow (CSF) on PC-CCMR
      as a measure of volumetric MBF before and after elective PCI.Methods and
      Results:We prospectively studied 34 patients with stable angina undergoing
      elective PCI for a single de novo lesion. Breath-hold PC-CCMR of CS was acquired
      to assess CSF and coronary flow reserve (CFR) at rest and during maximum
      hyperemia both before and after PCI (median, 3 days before PCI and 10 days after
      PCI, respectively). In total, hyperemic CSF increased significantly after PCI
      (before PCI, median, 2.3 mL/min/g [IQR, 1.5-3.2 mL/min/g] after PCI, 3.0 [1.8
      3.7] mL/min/g), although 13 patients (38.2%) had a decrease despite successful
      PCI and fractional flow reserve (FFR) improvement. Global CFR also significantly
      increased from a median of 2.5 (IQR, 1.5-3.5) to 3.4 (IQR, 2.1-4.2), whereas 12
      patients had decreased CFR after PCI. Pre-PCI hyperemic CSF was the only
      independent factor of change in CSF following PCI. CONCLUSIONS: Serial PC-CCMR of
      CS as a measure of change in absolute MBF is feasible. Uncomplicated PCI does not
      necessarily increase hyperemic global MBF, despite regional FFR improvement.

PMID- 29643279
TI  - Comparison of Clinical Outcomes Between Ticagrelor and Prasugrel in Patients With
      ST-Segment Elevation Myocardial Infarction - Results From the Korea Acute
      Myocardial Infarction Registry-National Institutes of Health.
AB  - BACKGROUND: There is little information regarding comparison of ticagrelor and
      prasugrel in patients with ST-segment elevation myocardial infarction (STEMI). We
      sought to compare clinical outcomes between ticagrelor and prasugrel in
      STEMI.Methods and Results:A total of 1,440 patients with STEMI who underwent
      successful primary percutaneous coronary intervention were analyzed; the data
      were obtained from the Korea Acute Myocardial Infarction Registry-National
      Institutes of Health. Of the patients, 963 received ticagrelor, and 477 received
      prasugrel. The primary study endpoint was 12-month major adverse cardiac events
      (MACE), including cardiac death, myocardial infarction (MI), and target vessel
      revascularization (TVR). MACE occurred in 91 patients (6.3%) over the 1-year
      follow-up, and there were no differences in the incidence of MACE (hazard ratio
      [HR] 1.20, 95% confidence interval [CI] 0.76-1.91, P=0.438) between the 2 groups.
      Analysis by propensity score matching (429 pairs) did not significantly affect
      the results. The incidence of in-hospital major bleeding events was still
      comparable between the 2 groups (2.4% vs. 2.5%, odds ratio 0.75, 95% CI 0.30
      1.86, P=0.532), and there was no significant difference in the incidence of MACE
      (5.4% vs. 5.8%, HR 0.98, 95% CI 0.56-1.74, P=0.951) after matching. CONCLUSIONS:
      Ticagrelor and prasugrel showed similar efficacy and safety profiles for treating
      STEMI in this Korean multicenter registry.

PMID- 29643280
TI  - Molecular diversity of the faecal microbiota of Toy Poodles in Japan.
AB  - The intestinal microbiota was revealed with the recent advances in molecular
      techniques, such as high-throughput sequencing analysis. As a result, the
      microbial changes are thought to influence the health of humans and animals and
      such changes are affected by several factors including diet, genetics, age, sex,
      and diseases. Similar studies are being conducted in dogs, and the knowledge of
      intestinal microbiota in dogs is expanding. Nonetheless, basic information on
      intestinal microbiota in dogs is less than that of humans. Our aim was to study
      toy poodles (n=21), a popular companion dog, in terms of basic characteristics of
      the faecal microbiota by 16S rRNA gene barcoding analysis. In the faecal
      microbiota, Firmicutes, Bacteroidetes, Proteobacteria, and Fusobacteria were the
      dominant phyla (over 93.4% of faecal microbiota) regardless of the attributes of
      the dogs. In family level, Enterobacteriaceae, Bacteroidaceae, and
      Lachnospiraceae were most prevalent. In case of a dog with protein-losing
      enteropathy, the diversity of faecal microbiota was different between before and
      after treatment. This study provides basic information for studying on faecal
      microbiota in toy poodles.

PMID- 29643281
TI  - Absence of histopathological changes in the retina of zebrafish treated with
      sodium iodate.
AB  - In ophthalmological research, the use of zebrafish to investigate visual
      behaviors has been increasing, but can produce misleading, false-positive results
      if compounds adversely affect their motor functions or central nervous system.
      Therefore, histological analysis to identify a target organ is important in
      zebrafish toxicity assay. We investigated the retinal degeneration in zebrafish,
      using typical retinal toxicants, mainly sodium iodate and N-methyl-N-nitrosourea
      (MNU). No histopathological changes were found after sodium iodate exposure at
      1.0 mM for 5 or 7 days in the retina of larval, juvenile, and adult zebrafish.
      There were also no obvious histopathological changes in the retina of adult
      zebrafish at 0.1 mM, even after 30 days treatment with sodium iodate. In
      addition, many proliferating cell nuclear antigen-positive cells were found not
      only in the ciliary marginal zone, but also in the outer nuclear layer,
      especially in larval and juvenile zebrafish with or without sodium iodate
      exposure. However, the concentrations of iodine in the blood and the eyeballs of
      adult zebrafish increased remarkably after the treatment. General retinal damage
      emerged after MNU exposure at 150 mg/l for 60 min in adult zebrafish, but first
      pyknotic cells appeared in the inner nuclear layer and the ganglion cell layer.
      Our findings indicate that zebrafish retina have a different reactivity pattern
      from mammalian animals against some retinal toxicants, and in them it is
      difficult to detect histopathological changes.

PMID- 29643282
TI  - Safety and Efficacy of Subcutaneous Cardioverter Defibrillator in Patients at
      High Risk of Sudden Cardiac Death - Primary Japanese Experience.
AB  - BACKGROUND: The entirely subcutaneous implantable cardioverter defibrillator (S
      ICD) was introduced as a new alternative to conventional transvenous ICD (TV-ICD)
      in Japan in February 2016, but its safety and efficacy are unclear.Methods and
      Results:A total of 60 patients (48 men, median age, 60 years; IQR, 44-67 years;
      primary prevention, n=24) underwent S-ICD implantation between February 2016 and
      August 2017. The device pocket was formed in the intermuscular space between the
      serratus anterior muscle and the latissimus dorsi muscle, and the parasternal S
      ICD lead was placed according to pre-implant screening. Defibrillation test was
      performed in 56 patients (93%). Ventricular fibrillation (VF) was induced in 55
      patients and terminated by a single 65-J shock in all patients. The median time
      to shock therapy was 13.4 s (IQR, 12.1-14.9 s) and the median post-shock
      impedance of the S-ICD lead was 64 Omega (IQR, 58-77 Omega). There were no
      operation-related complications or subsequent infectious complications. During
      follow-up (median, 275 days; IQR, 107-421 days), 1 patient (1.7%) had appropriate
      shock for VF with successful termination, whereas 5 patients (8.3%) had
      inappropriate shock due to oversensing of myopotential (n=3) or T-wave (n=1), and
      detection of supraventricular tachycardia (n=1). CONCLUSIONS: S-ICD is a safe and
      effective alternative to conventional TV-ICD. The long-term safety and efficacy
      of the S-ICD need further investigation.

PMID- 29643284
TI  - [Detection of early pancreatic cancer:past, present and future initiatives].

PMID- 29643283
TI  - Analysis of microbial abundance and community composition in esophagus and
      intestinal tract of wild veined rapa whelk (Rapana venosa) by 16S rRNA gene
      sequencing.
AB  - The rapa whelk Rapana venosa is a commercially important gastropod in China, but
      a major invader worldwide. There is little information on the bacterial community
      composition in the digestive system of this species, despite the microflora has
      important roles in digestion, nutrition, disease resistance, and immune response.
      The present study investigated the bacterial flora community in the esophagus and
      intestinal tract of wild R. venosa by 16S rRNA gene sequencing. The esophagus and
      intestine had 1175 and 526 unique operational taxonomic units, respectively, with
      616 common to both tissues. The 10 most highly represented microbial genera in
      the esophagus were Mycoplasma, Bifidobacterium, Escherichia, Shewanella, Vibrio,
      Lactobacillus, Octadecabacter, Enterococcus, Streptococcus, and Sphingomonas,
      which accounted for 41.35% of microbes. In the intestine, the most abundant
      genera were Mycoplasma, Bifidobacterium, Escherichia, Shewanella, Vibrio,
      Psychrilyobacter, Peptoniphilus, Sporobacterium, Octadecabacter, and Mobiluncusin
      (representing 62.74% of total microbes). A linear discriminant analysis, coupled
      with effect size, revealed that 31 taxa were differentially represented in
      esophagus and intestine bacterial communities. These results demonstrate the
      diversity of microbiota in the esophagus and intestinal tract of R. venosa and
      provide a basis for investigations into the physiological and immunological roles
      of these microorganisms in whelk.

PMID- 29643285
TI  - [Social programs for early diagnosis of pancreatic cancer -establishment of
      network between special doctors and practicing doctors].

PMID- 29643286
TI  - [Selection of the high risk population for early detection of pancreas cancer].

PMID- 29643287
TI  - [A screening strategy for detecting early pancreatic cancer].

PMID- 29643288
TI  - [Histopathological features of early pancreatic cancer].

PMID- 29643289
TI  - ?

PMID- 29643290
TI  - [Screening for colorectal cancer using immunological fecal occult blood test in
      inpatients].
AB  - We investigated the usefulness of screening for colorectal cancer (CRC) using
      immunological fecal occult blood test (FOBT) in 472 scheduled inpatients (median
      age, 68.6 years) who underwent screening for CRC via FOBT (single stool sample)
      at our hospital. The recall rate for further examination was 26.6% (126/472), and
      the rate of patients who underwent further examination was only 34.9% (44/126).
      The overall colorectal neoplasm detection rate, overall CRC detection rate, and
      positive predictive value for CRC in inpatients were 5.5% (26/472), 1.4% (7/472),
      and 5.5% (7/126), respectively, which were higher than those of population-based
      screening for CRC. Screening for CRC using FOBT in inpatients is a non-invasive
      and efficient method to detect latent CRC.

PMID- 29643291
TI  - [Effectiveness of indocyanine green fluorescence in endoscopic marking in gastric
      cancer surgery:a feasibility study for replacing India ink].
AB  - When injected, indocyanine green (ICG) immediately combines with lipoproteins to
      fluoresce. Here, we studied whether ICG fluorescence is effective for endoscopic
      marking in gastric cancer surgery using a photodynamic eye (PDE) camera and
      fluorescent endoscope. An ICG solution was endoscopically injected into the
      submucosal layer of the gastric tumor 3 days before surgery. We observed the
      lesions using both a PDE camera and a fluorescent endoscope during laparotomy and
      laparoscopy, respectively;we also observed the fluorescent luminance and
      fluorescent size of the resected lesions. We could intraoperatively detect the
      size of the resected lesions in eight patients with early gastric cancer and six
      patients with advanced gastric cancer. We believe that the use of ICG
      fluorescence in endoscopic marking requires additional information, such as the
      volume of the ICG solution and the timing of the ICG injection.

PMID- 29643292
TI  - [A case of postoperative recurrent gastric cancer resembling esophageal achalasia
      diagnosed by staging laparoscopy].
AB  - A 65-year-old man underwent subtotal gastrectomy for advanced gastric cancer. The
      histological type of the cancer was signet-ring cell carcinoma, and the clinical
      stage was stage IB (T2N0M0). Three years after surgery, the patient had the
      following symptoms:dysphagia, odynophagia, and weight loss. Esophageal endoscopy
      and esophagography revealed a circular stenosis covered with the normal mucosa
      between the middle esophagus and the esophagogastric junction. Histologically,
      the samples obtained by staging laparoscopy revealed signet-ring cell carcinoma.
      Tucker's criteria are an important tool for differentiating secondary achalasia
      from primary achalasia with clinical value. Therefore, we suggest that staging
      laparoscopy is useful for the histological diagnosis of recurrent gastric cancer.

PMID- 29643293
TI  - [A case of non-cardiac chest pain caused by esophageal motility disorder observed
      on esophageal high-resolution manometry].
AB  - A 20-year-old man was referred to our hospital with dysphagia and chest pain.
      Heart disease was denied. No abnormality was observed in upper
      esophagogastroduodenoscopy and fluoroscopy;furthermore, no gastric acid-related
      symptoms were observed on combined esophageal multichannel intraluminal impedance
      and pH monitoring. Esophageal high-resolution manometry (HRM) performed by liquid
      swallow revealed normal peristalsis;however, HRM performed while the patient was
      taking solid meals showed abnormal contraction, and the patient simultaneously
      complained of chest pain. Therefore, we diagnosed this case as non-cardiac chest
      pain due to esophageal motility disorder.

PMID- 29643294
TI  - [A case of recurrent alpha-fetoprotein-producing gastric cancer with long-term
      survival treated with chemotherapy].

PMID- 29643295
TI  - Prevalence and etiology of mastitis in dairy cattle in El Oro Province, Ecuador.
AB  - This study described the occurrence of clinical and subclinical forms of mastitis
      in 250 cattle from 5 dairy farms around the cities of Santa Rosa and Machala, El
      Oro Province, Ecuador. Clinical mastitis (CM) was determined based on obvious
      changes in milk (mild), signs of inflammation in the udder (moderate), and/or
      generalized clinical symptoms (severe). Subclinical mastitis (SCM) was assessed
      using the California mastitis test. CM and SCM were detected in 30 (12.0%) and
      150 (60%) of the 250 tested cattle, respectively. Prevalence at the udder quarter
      level was 57.7% (577/1,000), which was higher among forequarters (369/577; 63.9%)
      than hindquarters. Of the 577 mastitic milk samples subjected to microbiological
      analysis, 35 were excluded due to contamination and 20 tested negative.
      Identification of bacterial isolates revealed that 33.3% of the 93 CM samples
      contained coliforms, 25.8% coagulase-positive staphylococci, 20.4% coagulase
      negative staphylococci (CNS), 9.7% streptococci, 7.5% Bacillus spp., and 3.2%
      Klebsiella spp. Bacterial profiling of the 429 SCM milk samples showed that 55.4%
      contained CNS, 22.1% Bacillus spp., 9.3% streptococci, and 6.1% coagulase
      positive staphylococci. In vitro antibiotic susceptibility testing of the
      obtained isolates indicated that all were susceptible to amoxicillin, ampicillin,
      cefotaxime, enrofloxacin, sulfamethoxazole-trimethoprim, gentamicin, and
      neomycin. No multidrug-resistant strains were observed.

PMID- 29643296
TI  - Phylogenetic relationship of Ornithobacterium rhinotracheale strains.
AB  - The bacterium Ornithobacterium rhinotracheale is associated with respiratory
      disease in wild birds and poultry. In this study, the phylogenetic analysis of
      nine reference strains of O. rhinotracheale belonging to serovars A to I, and
      eight Mexican isolates belonging to serovar A, was performed. The analysis was
      extended to include sequences from another 23 strains available in the public
      domain. The analysis showed that the 40 sequences formed six clusters, I to VI.
      All eight Mexican field isolates were placed in cluster I. One of the reference
      strains appears to present genetic diversity not previously recognized and was
      placed in a new genetic cluster. In conclusion, the phylogenetic analysis of O.
      rhinotracheale strains, based on the 16S rRNA gene, is a suitable tool for
      epidemiologic studies.

PMID- 29643300
TI  - Copper Ion Sensing.

PMID- 29643297
TI  - Investigation of pharmacological responses to anti-diabetic drugs in female
      Spontaneously Diabetic Torii (SDT) fatty rats, a new nonalcoholic steatohepatitis
      (NASH) model.
AB  - Nonalcoholic steatohepatitis (NASH) is a progressive liver disease, and some
      patients develop hepatic cirrhosis/carcinoma. Animal models play key roles in the
      development of new therapies for NASH. In this study, the pharmacological effects
      of metformin and pioglitazone were investigated in female Spontaneously Diabetic
      Torii (SDT) fatty rats to verify the utility of this model. The anti-diabetic
      drugs were administered to SDT fatty rats fed a cholesterol-enriched diet from 4
      to 25 weeks, and changes in food intake, body weight, and blood chemistry
      parameters were evaluated every 4 weeks. The hepatic lipid content, mRNA
      expression in relation to lipid synthesis, inflammation, and fibrosis, and
      histopathological analyses were performed at 25 weeks. Pioglitazone improved
      hyperglycemia, hyperlipidemia, and abnormalities in hepatic parameters. The
      insulin levels were lower than those in the control rats before 16 weeks. Plasma
      glucose levels in the metformin-treated rats were lower than those in the control
      rats, and plasma alanine aminotransferase levels temporarily decreased. The lipid
      content and some mRNA expression in relation to fibrosis in the liver decreased
      with pioglitazone treatment, and the mRNA expression of microsomal triglyceride
      transfer protein increased. Hepatic fibrosis observed in the SDT fatty rats
      improved with pioglitazone treatment; however, the effect with metformin
      treatment was partial. These results in both drugs are in line with results in
      the human study, suggesting that the SDT fatty rat is useful for developing new
      anti-NASH drugs that show potential to regulate glucose/lipid metabolism.

PMID- 29643301
TI  - Current Mass Spectrometric Tools for the Bioanalyses of Therapeutic Monoclonal
      Antibodies and Antibody-Drug Conjugates.
AB  - The increase in the use of therapeutic monoclonal antibodies (mAbs) and antibody
      drug conjugates (ADCs) has made the detailed bioanalysis of these drugs essential
      not only for planning optimal therapeutic programs for clinical practice, but
      also for evaluating the biological equivalencies in the development of other
      biosimilars. The ligand binding assays that are widely in use now are being
      replaced rapidly by the highly accurate, sensitive, and selective analytical
      method using a mass spectrometer. This review will discuss the progress in and
      challenges observed during the development of a mass spectrometry-based
      bioanalytical method for therapeutic mAbs and ADCs.

PMID- 29643302
TI  - Rapid Determination of Two Triterpenoid Acids in Chaenomelis Fructus Using
      Supercritical Fluid Extraction On-line Coupled with Supercritical Fluid
      Chromatography.
AB  - In this study, an on-line supercritical fluid extraction (SFE) and supercritical
      fluid chromatography (SFC) method was developed for the rapid determination of
      oleanoic acid and ursolic acid in Chaenomelis Fructus. After optimization of the
      conditions, the two triterpenoid acids was obtained by SFE using 20% methanol as
      a modifier at 35 degrees C in 8 min. They were resolved on a Shim-pack UC-X Diol
      column (4.6 * 150 mm, 3 MUm) in 14 min (0 - 10 min, 5 - 10%; 10 - 14 min, 10%
      methanol in CO2) with a backpressure of 15 MPa at 40 degrees C. The on-line SFE
      SFC method could be completed within 40 min (10.79 mg/g dry plant, Rs = 2.36),
      while the ultrasound-assisted extraction and HPLC method required at least 90 min
      (3.55 mg/g dry plant, Rs = 1.92). This on-line SFE-SFC method is powerful to
      simplify the pre-processing and quantitative analysis of natural products.

PMID- 29643303
TI  - Fast Detection of Bismerthiazol in Cabbage Based on Fluorescence Quenching of
      Protein-Capping Gold Nanoclusters.
AB  - In this work, bismerthiazol was firstly assayed by a fast and portable method
      employing protein-capping gold nanoculsters as probes. The luminescent intensity
      of the nanoclusters showed a correlative response towards bismerthiazol from 5 to
      4000 MUg/mL with a linear relation in the range of 5 - 100 MUg/mL. As little as 5
      MUg/mL of bismerthiazol could be quantified. The high affinity of bismerthiazol
      to interact with the soybean protein-capped gold nanoclusters contributed to the
      excellent selectivity of this method over other common pesticides. The recoveries
      in several cabbage samples were 101 - 135%, indicating good performance in
      practical applications. By comparison to previous reported approaches, this
      method bears advantages including simple operation, fast response, visual readout
      and good selectivity.

PMID- 29643304
TI  - Determination of Anthracene in Water Samples by ELISA Using AhR Binding.
AB  - The degradation of polycyclic aromatic hydrocarbons (PAHs) can generate AhR
      binding compounds, exhibiting genotoxicity and carcinogenicity. In this
      investigation, aryl hydrocarbon receptor (AhR) from carp and anthracene (Ant)
      were coupled as antigen to establish an indirect competition ELISA (ic-ELISA)
      with an AhR-Ant antibody. A standard curve was determined for the ic-ELISA
      concerning detection range and limit. Also, the specificity, stability and the
      recovery of the ic-ELISA were checked. Results indicate that the ratio of
      antibody to antigen titer is 1:64000. The resulting standard curve is Y = 21.326
      * X + 1.8213. The detection range lies within 10 - 1000 ng mL-1 and the limiting
      concentration is 2.43 ng mL-1. The cross reaction ratio (CR) between Ant and
      naphthalene (Nap), Ant and phenanthrene (Phe) or Ant and fluoranthene (Flu) were
      5.7, 19.1 and less than 0.1%, respectively. The range of the coefficient of
      variance (C.V) amounts was from 4.2 up to 9.5% and the recovery range was from 90
      to 115%. These results show that the AhR-Ant ic-ELISA is sensitive, and can be
      used as a technical support to quantify Ant in the environment.

PMID- 29643305
TI  - An Ascorbic Acid Oxidase-based Sensing Platform for Stereoselective Interaction
      with Ascorbic Acid and Isoascorbic Acid.
AB  - A simple enzyme-based nanohybrid material was fabricated via immobilizing
      ascorbic acid oxidase (AO) on the surface of flower-like electrodeposited gold
      nanoparticles (dpAu) and reduced graphene oxide (rGO) modified glassy carbon
      electrodes (GCEs). The composite material was used for stereoselective
      interaction with ascorbic acid (AA) and isoascorbic acid (IAA). Herein, AO was
      applied as a stereoselective selector, and the dpAu/rGO nanohybrid not only acted
      as a supporter for high loading of AO, but also served as the nanomaterial for
      signal amplification. The results showed obvious peak current differences between
      AA and IAA, indicating that this strategy could be employed to recognize AA and
      IAA. Under the optimum conditions, the sensor exhibited a good linear response to
      AA and IAA in a linear range of 1.0 * 10-4 - 5.0 * 10-3 M. This approach with the
      merits of simplicity and rapid response provided a promising perspective for
      identification of AA and IAA.

PMID- 29643306
TI  - Hyperbranched Polyglycerol Functionalized Silica Stationary Phase for Hydrophilic
      Interaction Liquid Chromatography.
AB  - Surface-initiated anionic-ring-opening multibranching polymerization was employed
      to prepare a hyperbranched polyglycerol (HPG) functionalized silica stationary
      phase for hydrophilic interaction liquid chromatography (HILIC). The obtained
      stationary phase was characterized by Fourier-transform infrared spectrometry (FT
      IR) and thermogravimetric analysis (TGA). The chromatographic properties of the
      prepared stationary phase were systematically investigated. The abundance and
      multitude distribution of hydroxyl groups in HPG endowed the stationary phase
      with improved hydrophilicity and enhanced separation performance compared with
      the stationary phase functionalized with monolayer of hydroxyl groups. The
      stationary phase showed excellent retention of various polar compounds, such as
      nucleosides, necleobases, phenols and sulfanilamides, indicating great potential
      in the separation of complex biosamples.

PMID- 29643307
TI  - Quantification of Trans-resveratrol in Red Wines Using QuEChERS Extraction
      Combined with Liquid Chromatography-Tandem Mass Spectrometry.
AB  - Resveratrol is one of representative ingredient in red wine, but its
      quantification is a challenge because of a complex and abundant matrix. In this
      study, two sample pretreatments, direct dilution and QuEChERS extraction,
      coupling LCMS analysis were examined for resveratrol quantification. Similar
      recoveries of 106.4 to 93.7% were obtained for direct dilution and QuEChERS,
      respectively. With the aid of condition optimization, QuEChERS extraction could
      concentrate the resveratrol from red wines to improve the detection sensitivity
      with a LOD value of 2.5 ng/mL, which is four-times greater than the direct
      dilution approach. As a result, the QuEChERS method can provide a high linearity
      within the concentration range of 5 - 500 ng/mL, in which direct dilution
      produced the linear calibration curve within the concentrations of 25 - 500
      ng/mL. A high consistency was obtained for both approaches in which intra-day
      precisions were within 0.5 to 7.2% (n = 3), and the inter-day precisions were
      within 7.8 to 16.0% (n = 9). Overall, the sample pretreatment of QuEChERS can
      effectively reduce the matrix effect, which leads LCMS to quantify the low
      resveratrol abundance of 8.0 ppb in each red wine sample, which is not achieved
      with the direct dilution approach.

PMID- 29643308
TI  - Porous Organic Cage Embedded C18 Amide Silica Stationary Phase for High
      Performance Liquid Chromatography.
AB  - Reduced imine cage (RCC3) was first adopted for the preparation of porous organic
      cage embedded C18 amide silica stationary phase for high performance liquid
      chromatography. The prepared stationary phase was characterized by scanning
      electron microscope (SEM) and Fourier transformation infrared spectrum (FT-IR).
      Its chromatographic performance under reversed-phase mode was investigated in
      detail and compared with that of an ODS column. Multiple interactions, including
      hydrophobic interaction, pi-pi interactions, electrostatic interactions and
      hydrogen bonding, were involved due to the synergism of the C18 chain and RCC3.
      The column showed typical methylene selectivity and enhanced aromatic selectivity
      for nonpolar analytes while demonstrating high selectivity for polar analytes. In
      addition, the stationary phase showed the capability of separation of polar and
      hydrophilic compounds under per aqueous liquid chromatography mode (PALC),
      providing a green and economical way for the separation of polar and hydrophilic
      compounds. These results indicated the great application potential of the
      prepared stationary phase in the analysis of complex samples.

PMID- 29643309
TI  - A Colorimetric and Fluorescent Probe for the Detection of Cu2+ in a Complete
      Aqueous Solution.
AB  - The fluorescent probe has become an important method for the detection of heavy
      metal ions. In the present work, a new and simple fluorescent probe, Cu-P, for
      detecting copper ion (Cu2+) was designed and synthesized. The probe has shown
      high sensitivity and selectivity toward Cu2+. The detection limit was 13 nM
      (based on the 3sigma/slope). A significant color change from yellow to pink was
      observed; thus, the probe Cu-P could serve as a "naked-eye" indicator for Cu2+.
      Furthermore, the proposed probe was used to detect Cu2+ in real water and soil
      extract samples, with the result being satisfactory. Therefore, our proposed
      probe would provide a promising method for the detection of Cu2+ in the
      environment.

PMID- 29643310
TI  - Nanomolar Determination of Hydrogen Peroxide in Coastal Seawater Based on the
      Fenton Reaction with Terephthalate.
AB  - A non-enzymatic fluorescence method for the determination of hydrogen peroxide
      (H2O2) was investigated. This method is based on the hydroxylation reaction of
      terephthalate (TP) by hydroxyl radical formed from reaction between H2O2 and
      Fe(II), resulting in the formation of a strongly fluorescent 2
      hydroxyterephthalate (HTP). Under optimized conditions, a 3 nM detection limit
      and 1.0% precision at 200 nM were obtained. This was sensitive enough to
      determine the concentrations of H2O2 in coastal marine environments. The slopes
      of the calibration curve in seawater were nearly the same as those in Milli-Q
      water, suggesting that the fluorescent intensity was not affected by coexisting
      sea salts. However, the presence of nitrite at more than 10 MUM interfered with
      the formation of HTP. The developed method was successfully applied to determine
      the concentrations of H2O2 in Osaka Bay on the research vessel. The results
      obtained in Osaka Bay demonstrated that H2O2 was photochemically produced via the
      photolysis of dissolved organic matter supplied from the river with fresh water
      at the surface layer.

PMID- 29643311
TI  - Changes in the Structural Features of Organic Matter Extracted from Compost by
      the Seawater during a 90-day Period under Anaerobic Conditions, and Its Effect on
      Oogenesis of Brown Macroalga.
AB  - Seawater-extractable organic matter (SWEOM) has a potential to serve as an Fe
      complexing agent in an Fe-fertilizer intended to restore and preserve macroalgal
      forests. To better understand the restoration technique, structural alterations
      in SWEOM that occurred during a 90-day period of incubation in seawater were
      determined. Up to 82% of the total eluted SWEOM occurred during the initial 30
      days; a small amount of SWEOM then continued to elute during the next 60 days.
      Spectroscopic analyses showed that the high-molecular-weight SWEOM fraction (HMW)
      altered in aliphatic-rich materials, while the low-molecular-weight fraction
      (LMW) became significantly enriched in aromatic structures. The structural
      alterations in the HMW and LMW could be caused by the action of anaerobic
      microorganisms. In addition, approximately 30 and 60% of the gametophytes were
      converted to eggs in the presence of HMW and LMW with Fe, respectively.

PMID- 29643312
TI  - Determination of Dissolved Silica in Seawater by Ion-exclusion Chromatography
      with Post-column Derivatization/Silicomolybdenum Yellow Detection.
AB  - The determination of dissolved silica in seawater was investigated by an ion
      exclusion chromatography with a post-column derivatization/silicomolybdenum
      yellow method. To determine dissolved silica in seawater accurately, the
      experimental conditions, such as the volume of a reaction coil, the eluent
      concentration and the sample dilution factor, were optimized. This is the first
      report that has examined the details of the experimental condition for the
      measurement of dissolved silica in seawater by ion-exclusion chromatography with
      silicomolybdenum-yellow detection. The developed method was compared with the
      widely used continuous flow analysis and an ion-exclusion chromatography isotope
      dilution inductively coupled plasma mass spectrometry, which is a primary method
      of measurement. The analytical results by the three methods were in good
      agreement, considering the expanded uncertainty with a coverage factor, 2. The
      validity of the three methods was confirmed with each other. The developed method
      can give a quantitative value with less than 1% of the expanded uncertainty, and
      can be used for the determination of dissolved silica in candidate reference
      materials having a seawater matrix.

PMID- 29643313
TI  - Development of an Analytical System Based on a Magneto-pneumatic Oxygen Analyzer
      for Atmospheric Oxygen Determination.
AB  - A high-precision analytical system to observe the variations in the amount
      fractions of atmospheric oxygen with a very small uncertainty was developed. The
      system comprises a magneto-pneumatic oxygen analyzer and three automatic pressure
      controllers. The drift of the analyzer's signal intensity can be reduced when the
      amount fractions of oxygen in the sample and reference gases are similar because
      the temperature coefficient of the analyzer linearly depends on the difference
      between these amount fractions. The repeatability of oxygen determination and the
      long-term stability of the system were tested to assess the applicability of the
      analyzer to field-based measurements for continuous atmospheric observations. The
      standard deviation of the average for 10-min measurements in the 5-day long-term
      stability test was 0.7 MUmol mol-1 after a temperature correction. This indicates
      that the system can continuously measure the amount fractions of oxygen in the
      atmosphere for a few days without interruption for any calibration and/or
      compensation for the signal drift.

PMID- 29643314
TI  - Ultra-sensitive Trace-Water Optical Sensor with In situ- synthesized Metal
      Organic Framework in Glass Paper.
AB  - Monitoring of trace water in industrial gases is strongly recommended because
      contaminants cause serious problems during use, especially in the semiconductor
      industry. An ultra-sensitive trace-water sensor was developed with an in situ
      synthesized metal-organic framework as the sensing material. The sample gas is
      passed through the sensing membrane and efficiently and rapidly collected by the
      sensing material in the newly designed gas collection/detection cell. The sensing
      membrane, glass paper impregnated with copper 1,3,5-benzenetricarboxylate (Cu
      BTC), is also newly developed. The amount and density of the sensing material in
      the sensing membrane must be well balanced to achieve rapid and sensitive
      responses. In the present study, Cu-BTC was synthesized in situ in glass paper.
      The developed system gave high sensing performances with a limit of detection
      (signal/noise ratio = 3) of 9 parts per billion by volume (ppbv) H2O and a 90%
      response time of 86 s for 200 ppbv H2O. The reproducibility of the responses
      within and between lots had relative standard deviations for 500 ppbv H2O of 0.8%
      (n = 10) and 1.5% (n = 3), respectively. The long-term (2 weeks) stability was
      7.3% for 400 ppbv H2O and one-year continuous monitoring test showed the
      sensitivity change of <~3% before and after the study. Furthermore, the system
      response was in good agreement with the response achieved in cavity ring-down
      spectroscopy. These performances are sufficient for monitoring trace water in
      industrial gases. The integrated system with light and gas transparent structure
      for gas collection/absorbance detection can also be used for other target gases,
      using specific metal-organic frameworks.

PMID- 29643315
TI  - A Dual Alkylated Peptide-ligand Enhances Affinity to Human Serum Albumin.
AB  - Therapeutic peptides and diagnostic agents with their molecular size below the
      renal clearance threshold suffer from short blood circulation time. Here, we
      report a novel design of peptide-based ligand with a strong binding affinity to
      human serum albumin (HSA), which can be used as a tag to extend the blood
      circulation of small-size molecules. We designed ligands with dual alkyl groups
      connected with a negatively charged spacer. The ligands showed both higher
      binding affinity to HSA and a higher retention in mice blood than that of a
      single alkylated peptide.

PMID- 29643316
TI  - Determination of Blood Plasma Aminothiols Using Derivatization-enhanced Capillary
      Transient Isotachophoresis.
AB  - A sensitive capillary electrophoresis method was developed for the determination
      of aminothiol (cysteine, homocysteine, and glutathione) total levels in human
      blood plasma. Analytes were derivatized with Ellman's reagent (5,5'-dithiobis(2
      nitrobenzoic acid)) after reduction with dithiothreitol. Liquid-liquid extraction
      was applied to purify the samples and concentrate the analytes. Total analysis
      time was 7.5 min using a silica capillary (50 MUm i.d.; effective separation
      length 23.5 cm). Electrophoretic separation was performed using 50 mM citric acid
      with 20 mM triethanolamine (pH 3) containing 2% Ficoll 400. Detection limit was
      0.8 MUM for glutathione and 0.3 MUM for both cysteine and homocysteine. Accuracy
      was 94 - 107%, repeatability and reproducibility were ca. 2.7 - 3.5 and 2.5 -
      6.5%, respectively.

PMID- 29643318
TI  - Plasma Xanthine Oxidoreductase Activity as a Novel Biomarker of Metabolic
      Disorders in a General Population.
AB  - BACKGROUND: Xanthine oxidoreductase (XOR) is an enzyme that catalyzes the
      formation of uric acid from hypoxanthine and xanthine, leading to an increase in
      superoxide and reactive oxygen species. Activation of XOR promotes oxidative
      stress-related tissue injury. We investigated the associations between metabolic
      parameters and plasma XOR activity measured by a sensitive and accurate assay
      using a combination of liquid chromatography and triple quadrupole mass
      spectrometry to detect [13C2,15N2]-uric acid using [13C2,15N2]-xanthine as a
      substrate.Methods and Results:A total of 627 Japanese subjects (M/F, 292/335)
      from the Tanno-Sobetsu Study, a population-based cohort, were recruited. Plasma
      XOR activity was significantly higher in males than in females, and habitual
      smoking was associated with elevation of activity. Plasma XOR activity was
      positively correlated with body mass index (BMI; r=0.323, P<0.001), waist
      circumference, blood pressure, and levels of liver enzymes including alanine
      transaminase (r=0.694, P<0.001), uric acid (r=0.249, P<0.001), triglycerides
      (r=0.312, P<0.001), hemoglobin A1c, fasting glucose, insulin and HOMA-R (r=0.238,
      P<0.001) as a marker of insulin resistance and was negatively correlated with
      high-density lipoprotein cholesterol level. On stepwise and multivariate
      regression analyses, BMI, smoking and levels of alanine transaminase, uric acid,
      triglycerides and HOMA-R were independent predictors of plasma XOR activity after
      adjustment for age and gender. CONCLUSIONS: Plasma XOR activity is a novel
      biomarker of metabolic disorders in a general population.

PMID- 29643319
TI  - Should Measures of High-Density Lipoprotein Function Be Added to the Low-Density
      Lipoprotein Cholesterol Target Level-Based Guidelines for Prevention of
      Atherosclerotic Disease?

PMID- 29643320
TI  - Announcement of the 2018 JCS Meeting Activities (2).

PMID- 29643321
TI  - Clinical and molecular characterization of 5alpha-reductase type 2 deficiency due
      to mutations (p.Q6X, p.R246Q) in SRD5A2 gene.
AB  - Early diagnosis and optimal management for steroid 5alpha-reductase type 2
      deficiency (5alpha-RD2) patients are major challenges for clinicians and mutation
      analysis for the 5alpha-reductase type 2 (SRD5A2) gene is the golden standard for
      the diagnosis of the disease. In silico analysis of this enzyme has not been
      reported due to the lack of appropriate model. Moreover, the histological and
      pathological changes of the gonads are largely unknown. In the present study, a
      5alpha-RD2 patient born with abnormal external genitalia was studied and mutation
      analysis for SRD5A2 gene was conducted. Moreover, we constructed the homology
      modeling of 5alpha-reductase using SWISS-MODEL, followed by the molecular docking
      study. Furthermore, immunohistochemical staining of Ki67 for the testes tissue
      was conducted to investigate the potential pathological characteristics. The
      patient had male (46, XY) chromosomes but presented female characteristics, and
      the mutation analysis identified a heterozygotes mutation (p.Q6X, p.R246Q) in
      SRD5A2 gene. In silico analysis elucidated the potential effect of the mutation
      on enzyme activity. Immunohistochemical staining for the excised testes showed
      that 30%-50% of the germ cells were Ki67 positive, which indicated the early
      neoplastic potential. In conclusion, we analyzed the genotype-phenotype
      correlations of 5alpha-RD2 caused by a heterozygotes mutation (p.Q6X, p.R246Q).
      Importantly, we conducted the homology modeling and molecular docking for the
      first time, which provided a homology model for further investigations.
      Immunohistochemical results suggested gonadectomy or testis descent should be
      performed early for 5alpha-RD2 patient, as delayed treatment would have
      maintained the testes in a tumorigenic condition.

PMID- 29643322
TI  - Metabolically healthy obesity and risk of leukoaraiosis; a population based cross
      sectional study.
AB  - Metabolically healthy obese (MHO) individual is known to be defended from the
      metabolic complications of obesity. Leukoaraiosis, which is commonly detected on
      brain magnetic resonance imaging (MRI), is now recognized as a risk of stroke,
      dementia and death. However, the association between MHO and the prevalence of
      leukoaraiosis is unclear. In this cross-sectional study of 796 participants who
      received a medical examination program, we investigated the association between
      MHO and the prevalence of leukoaraiosis. We used common clinical markers for
      definition of metabolic healthy status: blood pressure, fasting plasma glucose,
      triglycerides and high-density lipoprotein cholesterol concentrations. Obesity
      was defined by body mass index >=25.0 kg/m2. We diagnosed leukoaraiosis by fluid
      attenuated inversion recovery without hypointensity on T1-weighted images or the
      presence of a hyperintensity on T2-weighted images. The crude prevalence
      proportion of leukoaraiosis was 44.5% (case/n = 171/384) in metabolically healthy
      nonobese (MHNO) individual, 46.3% (44/95) in MHO individual, 62.3% (114/183) in
      metabolically unhealthy nonobese (MUNO) individual or 56.6% (77/136) in MUO
      individual. The odds ratios of prevalence of leukoaraiosis were 1.19 (95% CI 0.74
      1.90, p = 0.471) for MHO, 1.79 (1.22-2.62, p = 0.003) for MUNO and 1.56 (1.03
      2.37, p = 0.037) for MUO individuals after adjusting for sex, age, smoking
      statues, habit of exercise and alcohol, compared with MHNO individual. We
      revealed that MHO individuals were not related with the higher risk of
      leukoaraiosis, whereas MUNO and MUO individuals were.

PMID- 29643323
TI  - Effects of linagliptin versus voglibose on treatment-related quality of life in
      patients with type 2 diabetes: sub-analysis of the L-STEP study.
AB  - Treatment-related quality of life (QOL) is an important aspect of diabetes
      management. However, no studies have compared the influence of dipeptidyl
      peptidase-4 inhibitors versus alpha-glucosidase inhibitors on treatment-related
      QOL. This prespecified sub-analysis of the Linagliptin Study of Effects on
      Postprandial blood glucose (L-STEP) compared the effects of linagliptin (5 mg
      once daily) and voglibose (0.2 mg/meal thrice daily) on treatment-related QOL in
      Japanese patients with type 2 diabetes (T2DM) inadequately controlled with diet
      and exercise therapy. Among 366 subjects in the original study, 182 in the
      linagliptin group and 173 in the voglibose group were included in this analysis.
      The outcome of this study was change in QOL as assessed by the Diabetes Therapy
      Related Quality of Life 17 (DTR-QOL17) questionnaire from baseline to week 12.
      Compared with baseline data, total DTR-QOL17 scores were significantly higher
      after 12 weeks of linagliptin and voglibose treatment. The change in the total
      DTR-QOL17 score and the score of one domain, burden on social activities and
      daily activities, was significantly greater in the linagliptin group than in the
      voglibose group. In addition, only linagliptin treatment was identified as a
      factor associated with an increased total DTR-QOL17 score. Linagliptin is
      superior to voglibose in terms of improving treatment-related QOL in Japanese
      patients with T2DM.

PMID- 29643324
TI  - Conversion of Curcumin into Heterocyclic Compounds as Potent Anti-diabetic and
      Anti-histamine Agents.
AB  - Potential biologically active derivatives of the curcumin were prepared by the
      cyclocondensation reaction cyclohexanone 2, imino pyrimidine 3, pyrmidinones 4,
      thiopyrimidine 6 and pyranone 5, 7 when treated with acetylacetone, guanidine,
      ureaethylcyanoacetate, thiourea and ethylacetoacetate, respectively. The
      structures of compounds (2-7) were elucidated by means of microanalysis as well
      as spectral measurements such as IR, 1H-NMR, MS. The anti-diabetic potential of
      curcumin derivatives were evaluated by assessing amylase inhibition assay, also
      inhibition of histamine release activity of curcumin derivatives were assessed by
      U937 human monocytes. The results for amylase inhibition activity revels that the
      curcumin inhibits alpha-amylase in a concentration dependent manner. Compounds 4
      and 5 exhibited significant inhibitory activity against amylase enzyme and was
      comparable with that of acrabose. Also, compounds 5, 6 and 7 exhibited
      significant inhibitory activity against histamine. Our results concluded that
      curcumin pyrmidinones and pyranone derivatives have highly effects as anti
      diabetic and anti-histamine activities.

PMID- 29643325
TI  - A new species of the genus Leptolalax (Anura: Megophryidae) from southern
      Vietnam.
AB  - We describe a new species of megophryid frog from Phu Yen Province in southern
      Vietnam. Leptolalax macrops sp. nov. is distinguished from its congeners by a
      combination of the following morphological attributes: (1) body size medium (SVL
      28.0-29.3 mm in three adult males, 30.3 mm in single adult female); (2) supra
      axillary glands present, creamy white; ventrolateral glands indistinct; (3)
      tympanum externally distinct; (4) dorsal skin roughly granular with larger
      tubercles, dermal ridges on dorsum absent; (5) rudimentary webbing present
      between fingers I-II and II-III; rudimentary webbing between all toes; fingers
      and toes without dermal fringes; (6) in life ventral surface greyish-violet with
      white speckling; (7) supratympanic fold distinct, dark brown in life; (8) iris
      bicolored, typically golden in upper half, fading to golden green in lower half;
      (9) tibia short (TbL/SVL 0.44-0.45 in males); and (10) eyes large and protuberant
      (ED/SVL 0.15-0.16 in males). From all congeners for which comparable sequences
      are available, the new species differs markedly in the 16S rRNA mitochondrial
      gene sequence (P-distance>5.7%). The new species is currently known only from
      montane evergreen tropical forests of Song Hinh District, Phu Yen Province, and
      M'Drak District of Dak Lak Province at elevations of 470-630 m a.s.l. We suggest
      the new species should be considered as Data Deficient following the IUCN's Red
      List categories. We also report a previously unknown Leptolalax mtDNA lineage
      from an evergreen tropical forest in the Hoa Thinh District of Phu Yen Province,
      which may also represent an undescribed species.

PMID- 29643326
TI  - Identification and characterization of short tandem repeats in the Tibetan
      macaque genome based on resequencing data.
AB  - The Tibetan macaque, which is endemic to China, is currently listed as a Near
      Endangered primate species by the International Union for Conservation of Nature
      (IUCN). Short tandem repeats (STRs) refer to repetitive elements of genome
      sequence that range in length from 1-6 bp. They are found in many organisms and
      are widely applied in population genetic studies. To clarify the distribution
      characteristics of genome-wide STRs and understand their variation among Tibetan
      macaques, we conducted a genome-wide survey of STRs with next-generation
      sequencing of five macaque samples. A total of 1 077 790 perfect STRs were mined
      from our assembly, with an N50 of 4 966 bp. Mono-nucleotide repeats were the most
      abundant, followed by tetra- and di-nucleotide repeats. Analysis of GC content
      and repeats showed consistent results with other macaques. Furthermore, using STR
      analysis software (lobSTR), we found that the proportion of base pair deletions
      in the STRs was greater than that of insertions in the five Tibetan macaque
      individuals (P<0.05, t-test). We also found a greater number of homozygous STRs
      than heterozygous STRs (P<0.05, t-test), with the Emei and Jianyang Tibetan
      macaques showing more heterozygous loci than Huangshan Tibetan macaques. The
      proportion of insertions and mean variation of alleles in the Emei and Jianyang
      individuals were slightly higher than those in the Huangshan individuals, thus
      revealing differences in STR allele size between the two populations. The
      polymorphic STR loci identified based on the reference genome showed good
      amplification efficiency and could be used to study population genetics in
      Tibetan macaques. The neighbor-joining tree classified the five macaques into two
      different branches according to their geographical origin, indicating high
      genetic differentiation between the Huangshan and Sichuan populations. We
      elucidated the distribution characteristics of STRs in the Tibetan macaque genome
      and provided an effective method for screening polymorphic STRs. Our results also
      lay a foundation for future genetic variation studies of macaques.

PMID- 29643327
TI  - Comparison of Effects of Vessel-Sealing Devices and Conventional Hemorrhoidectomy
      on Postoperative Pain and Quality of Life.
AB  - BACKGROUND The aim of this study was to investigate the early and late results of
      use of LigaSure, Harmonic Scalpel, and conventional hemorrhoidectomy in
      hemorrhoidectomy, to determine the least painful method, and to investigate the
      relationship between pain perception and personal differences in hemorrhoid
      bundles. MATERIAL AND METHODS Ninety patients undergoing hemorrhoidectomy between
      2014 and 2017 were retrospectively evaluated. We investigated the duration of
      hospitalization and the presence of bleeding, incontinence, perianal wetness,
      urinary retention, stenosis, and recurrence during follow-up after surgery.
      Analgesic requirement was determined by Patient-Controlled Analgesia, as well as
      pain score by use of the Visual Analog Score and patient satisfaction by Short
      Form-36. We also assessed the relationship between pain and lateral thermal
      damage, the number of peripheral nerves, number of excised bundles, and the
      number of thrombosed vessels, as determined by histopathological examination.
      RESULTS No differences were found among the 3 methods in the duration of
      hospitalization, the presence of bleeding, fecal incontinence, perianal wetness,
      urinal retention, anal stenosis, recurrence rate, VAS, analgesic consumption, or
      results of the SF-36. There was no difference in the number of bundles,
      thrombosed vessels, or number of nerve fibers in a bundle, but the LigaSure
      Hemorrhoidectomy had more lateral thermal damage (p<0.001). While there was a
      difference between VAS of day 1 and 7 according to the hemorrhoid bundles, there
      was no difference in the other parameters. CONCLUSIONS There was no difference
      among the 3 methods in terms of complications, postoperative pain, or patient
      satisfaction, and pain intensity was positively correlated with the number of
      excised bundles.

PMID- 29643328
TI  - Superior Mesenteric Artery Syndrome in Patients with Crohn's Disease: A
      Description of 2 Cases Studied with a Novel Magnetic Resonance Enterography (MRE)
      Procedure.
AB  - BACKGROUND Superior mesenteric artery syndrome is caused by vascular compression
      of the third portion of the duodenum between the aorta and the superior
      mesenteric artery. It may occur with acute or chronic symptomatology, such as
      vomiting or postprandial abdominal pain, and it is usually caused by a lack of
      mesenteric fat pad under conditions of severe weight loss. Crohn's disease can be
      one of them. CASE REPORT We report 2 cases of Crohn's disease patients with
      clinical suspicion of jejunal stricture who underwent MR-enterography with a
      novel approach. In fact, the examinations were performed including prone position
      of the patients inside the scanner, drinking of contrast medium during the
      examination, and prompt acquisition of fluoroscopic sequences. Both the exams
      showed an abrupt termination of the duodenum on its third portion and a decreased
      aortomesenteric distance, allowing the diagnosis of superior mesenteric artery
      syndrome. CONCLUSIONS A correlation between Crohn's disease and superior
      mesenteric artery syndrome has never before been reported in the literature. The
      present study provides some practical steps that may be useful in order to
      improve MRE standard protocol in recognizing this condition while evaluating
      Crohn's disease bowel lesions.

PMID- 29643329
TI  - Shared effects of DISC1 disruption and elevated WNT signaling in human cerebral
      organoids.
AB  - The development of three-dimensional culture methods has allowed for the study of
      developing cortical morphology in human cells. This provides a new tool to study
      the neurodevelopmental consequences of disease-associated mutations. Here, we
      study the effects of isogenic DISC1 mutation in cerebral organoids. DISC1 has
      been implicated in psychiatric disease based on genetic studies, including its
      interruption by a balanced translocation that increases the risk of major mental
      illness. Isogenic wild-type and DISC1-disrupted human-induced pluripotent stem
      cells were used to generate cerebral organoids, which were then examined for
      morphology and gene expression. We show that DISC1-mutant cerebral organoids
      display disorganized structural morphology and impaired proliferation, which is
      phenocopied by WNT agonism and rescued by WNT antagonism. Furthermore, there are
      many shared changes in gene expression with DISC1 disruption and WNT agonism,
      including in neural progenitor and cell fate markers, regulators of neuronal
      migration, and interneuron markers. These shared gene expression changes suggest
      mechanisms for the observed morphologic dysregulation with DISC1 disruption and
      points to new avenues for future studies. The shared changes in three-dimensional
      cerebral organoid morphology and gene expression with DISC1 interruption and WNT
      agonism further strengthens the link between DISC1 mutation, abnormalities in WNT
      signaling, and neuropsychiatric disease.

PMID- 29643330
TI  - Publisher Correction: Unravelling the immune signature of Plasmodium falciparum
      transmission-reducing immunity.
AB  - The original version of this Article contained errors in Fig. 3. In panel a, bars
      from a chart depicting the percentage of antibody-positive individuals in non
      infectious and infectious groups were inadvertently included in place of bars
      depicting the percentage of infectious individuals, as described in the Article
      and figure legend. However, the p values reported in the Figure and the resulting
      conclusions were based on the correct dataset. The corrected Fig. 3a now shows
      the percentage of infectious individuals in antibody-negative and -positive
      groups, in both the PDF and HTML versions of the Article. The incorrect and
      correct versions of Figure 3a are also presented for comparison in the
      accompanying Publisher Correction as Figure 1.The HTML version of the Article
      also omitted a link to Supplementary Data 6. The error has now been fixed and
      Supplementary Data 6 is available to download.

PMID- 29643331
TI  - Electroencephalographic delta/alpha frequency activity differentiates psychotic
      disorders: a study of schizophrenia, bipolar disorder and methamphetamine-induced
      psychotic disorder.
AB  - Electroencephalography (EEG) has been proposed as a neurophysiological biomarker
      to delineate psychotic disorders. It is known that increased delta and decreased
      alpha, which are apparent in psychosis, are indicative of inappropriate arousal
      state, which leads to reduced ability to attend to relevant information. On this
      premise, we investigated delta/alpha frequency activity, as this ratio of
      frequency activity may serve as an effective neurophysiological biomarker. The
      current study investigated differences in delta/alpha frequency activity, in
      schizophrenia (SCZ), bipolar I disorder with psychotic features and
      methamphetamine-induced psychosis. One hundred and nine participants, including
      individuals with SCZ (n = 28), bipolar I disorder with psychotic features (n =
      28), methamphetamine-induced psychotic disorder (MPD) (n = 24) and healthy
      controls (CON, n = 29). Diagnosis was ascertained with the Structured Clinical
      Interview for Diagnostic and Statistical Manual of Mental Disorders, 4th Edition
      disorders and current medication was recorded. EEG was undertaken in three
      testing conditions: resting eyes open, resting eyes closed and during completion
      of a simple cognitive task (visual continuous performance task). EEG delta/alpha
      frequency activity was investigated across these conditions. First, delta/alpha
      frequency activity during resting eyes closed was higher in SCZ and MPD globally,
      when compared to CON, then lower for bipolar disorder (BPD) than MPD for right
      hemisphere. Second, delta/alpha frequency activity during resting eyes open was
      higher in SCZ, BPD and MPD for all electrodes, except left frontal, when compared
      to CON. Third, delta/alpha frequency activity during the cognitive task was
      higher in BPD and MPD for all electrodes, except left frontal, when compared to
      CON. Assessment of EEG delta/alpha frequency activity supports the delineation of
      underlying neurophysiological mechanisms present in psychotic disorders, which
      are likely related to dysfunctional thalamo-cortical connectivity. Delta/alpha
      frequency activity may provide a useful neurophysiological biomarker to delineate
      psychotic disorders.

PMID- 29643332
TI  - Macrophage-derived IL-1beta/NF-kappaB signaling mediates parenteral nutrition
      associated cholestasis.
AB  - In infants intolerant of enteral feeding because of intestinal disease,
      parenteral nutrition may be associated with cholestasis, which can progress to
      end-stage liver disease. Here we show the function of hepatic macrophages and
      phytosterols in parenteral nutrition-associated cholestasis (PNAC) pathogenesis
      using a mouse model that recapitulates the human pathophysiology and combines
      intestinal injury with parenteral nutrition. We combine genetic, molecular, and
      pharmacological approaches to identify an essential function of hepatic
      macrophages and IL-1beta in PNAC. Pharmacological antagonism of  IL-1 signaling
      or genetic deficiency in CCR2, caspase-1 and caspase-11, or IL-1 receptor (which
      binds both IL-1alpha and IL-1beta) prevents PNAC in mice. IL-1beta increases
      hepatocyte NF-kappaB signaling, which interferes with farnesoid X receptor and
      liver X receptor bonding to respective promoters of canalicular bile and sterol
      transporter genes (Abcc2, Abcb11, and Abcg5/8), resulting in transcriptional
      suppression and subsequent cholestasis. Thus, hepatic macrophages, IL-1beta, or
      NF-kappaB may be targets for restoring bile and sterol transport to treat PNAC.

PMID- 29643334
TI  - Performance of the Trioplex real-time RT-PCR assay for detection of Zika, dengue,
      and chikungunya viruses.
AB  - The emergence and spread of Zika virus (ZIKV) presented a challenge to the
      diagnosis of ZIKV infections in areas with transmission of dengue (DENV) and
      chikungunya (CHIKV) viruses. To facilitate detection of ZIKV infections, and
      differentiate these infections from DENV and CHIKV, we developed the Trioplex
      real-time RT-PCR assay (Trioplex assay). Here, we describe the optimization of
      multiplex and singleplex formats of the assay for a variety of chemistries and
      instruments to facilitate global standardization and implementation. We evaluated
      the analytical performance of all Trioplex modalities for detection of these
      three pathogens in serum and whole blood, and for ZIKV in urine. The limit of
      detection for the three viruses and in different RNA-extraction modalities is
      near 103 genome copy equivalents per milliliter (GCE/mL). Simultaneous testing of
      more than one specimen type from each patient provides a 6.4% additional
      diagnostic sensitivity. Overall, the high sensitivity of the Trioplex assay
      demonstrates the utility of this assay ascertaining Zika cases.

PMID- 29643333
TI  - Srf destabilizes cellular identity by suppressing cell-type-specific gene
      expression programs.
AB  - Multicellular organisms consist of multiple cell types. The identity of these
      cells is primarily maintained by cell-type-specific gene expression programs;
      however, mechanisms that suppress these programs are poorly defined. Here we show
      that serum response factor (Srf), a transcription factor that is activated by
      various extracellular stimuli, can repress cell-type-specific genes and promote
      cellular reprogramming to pluripotency. Manipulations that decrease beta-actin
      monomer quantity result in the nuclear accumulation of Mkl1 and the activation of
      Srf, which downregulate cell-type-specific genes and alter the epigenetics of
      regulatory regions and chromatin organization. Mice overexpressing Srf exhibit
      various pathologies including an ulcerative colitis-like symptom and a metaplasia
      like phenotype in the pancreas. Our results demonstrate an unexpected function of
      Srf via a mechanism by which extracellular stimuli actively destabilize cell
      identity and suggest Srf involvement in a wide range of diseases.

PMID- 29643335
TI  - Quantitative characterization of all single amino acid variants of a viral capsid
      based drug delivery vehicle.
AB  - Self-assembling proteins are critical to biological systems and industrial
      technologies, but predicting how mutations affect self-assembly remains a
      significant challenge. Here, we report a technique, termed SyMAPS (Systematic
      Mutation and Assembled Particle Selection), that can be used to characterize the
      assembly competency of all single amino acid variants of a self-assembling viral
      structural protein. SyMAPS studies on the MS2 bacteriophage coat protein revealed
      a high-resolution fitness landscape that challenges some conventional assumptions
      of protein engineering. An additional round of selection identified a previously
      unknown variant (CP[T71H]) that is stable at neutral pH but less tolerant to
      acidic conditions than the wild-type coat protein. The capsids formed by this
      variant could be more amenable to disassembly in late endosomes or early
      lysosomes-a feature that is advantageous for delivery applications. In addition
      to providing a mutability blueprint for virus-like particles, SyMAPS can be
      readily applied to other self-assembling proteins.

PMID- 29643336
TI  - Identification of Morus notabilis MADS-box genes and elucidation of the roles of
      MnMADS33 during endodormancy.
AB  - The MADS-box genes encode transcriptional regulators with various functions
      especially during floral development. A total of 54 putative Morus notabilis MADS
      box genes (MnMADSs) were identified and phylogenetically classified as either
      type I (17 genes) or type II (37 genes). The detected genes included three
      FLOWERING LOCUS C-like (MnFLC-like) genes, MnMADS33, MnMADS50, and MnMADS7. MnFLC
      like proteins could directly or indirectly repress promoter activity of the
      mulberry FLOWERING LOCUS T-like (MnFT) gene. Transgenic Arabidopsis thaliana
      overexpressing MnFLC-like genes exhibited delayed flowering and down-regulated
      expression of FT and SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1 (SOC1). The gene
      expression analyses in floral bud indicated that MnMADS33 expression increased,
      while MnFT expression decreased during the induction of dormancy in response to
      cold conditions. Dormancy release resulted in the down-regulation of MnMADS33
      expression and the up-regulation of MnFT expression. Furthermore, abscisic acid
      promoted the transcription of MnMADS33 and MnFT, although the expression level of
      MnFT gradually decreased. These results are consistent with the hypothesis that
      MnMADS33 negatively regulated the expression of MnFT to repress dormancy release
      and flowering in mulberry. This study may be relevant for future investigations
      regarding the effects of MnMADS genes on mulberry flowering development.

PMID- 29643337
TI  - Association between hedonic hunger and body-mass index versus obesity status.
AB  - Obesity-associated differences in hedonic hunger, while consistently reported,
      have not been adequately quantified, with most studies failing to demonstrate
      strong correlations between Body Mass Index (BMI) and hedonic hunger indicators.
      Here, we quantified and assessed the nature of the relationship between hedonic
      hunger and BMI, in a cross-sectional study using the Portuguese version of the
      PFS (P-PFS) to measure hedonic hunger. Data were collected from 1266 participants
      belonging to non-clinical, clinical (candidates for weight-loss surgery) and
      population samples. Across samples, significant but weak positive associations
      were found between P-PFS scores and BMI, in adjusted linear regression models.
      However, in logistic regression models of data from the clinical and non-clinical
      samples, the P-PFS Food Available domain score was significantly and robustly
      associated with belonging to the clinical sample (OR = 1.8, 95%CI: 1.2-2.8; p =
      0.008), while in the population sample it was associated to being obese (OR =
      2.1, 95%CI: 1.6-2.7; p < 0.001). Thus, hedonic hunger levels are associated with
      obesity status with the odds of being obese approximately doubling for each unit
      increase in the P-PFS Food Available score.

PMID- 29643338
TI  - Causal Pathways from Blood Pressure to Larger Qrs Amplitudes a Mendelian
      Randomization Study.
AB  - Abnormal QRS duration and amplitudes on the electrocardiogram are indicative of
      cardiac pathology and are associated with adverse outcomes. The causal nature of
      these associations remains uncertain and could be due to QRS abnormalities being
      a symptom of cardiac damage rather than a factor on the causal pathway. By
      performing Mendelian randomization (MR) analyses using summary statistics of
      genome wide association study consortia with sample sizes between 20,687 and
      339,224 individuals, we aimed to determine which cardiovascular risk factors
      causally lead to changes in QRS duration and amplitude (Sokolow-Lyon, Cornell and
      12-leadsum products). Additionally, we aimed to determine whether QRS traits have
      a causal relationship with mortality and longevity. We performed inverse-variance
      weighted MR as main analyses and MR-Egger regression and weighted median
      estimation as sensitivity analyses. We found evidence for a causal relationship
      between higher blood pressure and larger QRS amplitudes (systolic blood pressure
      on Cornell: 55SNPs, causal effect estimate per 1 mmHg = 9.77
      millimeters.milliseconds (SE = 1.38,P = 1.20 * 10-12) and diastolic blood
      pressure on Cornell: 57SNPs, causal effect estimate per 1 mmHg = 14.89
      millimeters.milliseconds (SE = 1.82,P = 3.08 * 10-16), but not QRS duration.
      Genetically predicted QRS traits were not associated with longevity, suggesting a
      more prominent role of acquired factors in explaining the well-known link between
      QRS abnormalities and outcome.

PMID- 29643339
TI  - Desynchronization of diurnal rhythms in bipolar disorder and borderline
      personality disorder.
AB  - It has long been proposed that diurnal rhythms are disturbed in bipolar disorder
      (BD). Such changes are obvious in episodes of mania or depression. However,
      detailed study of patients between episodes has been rare and comparison with
      other psychiatric disorders rarer still. Our hypothesis was that evidence for
      desynchronization of diurnal rhythms would be evident in BD and that we could
      test the specificity of any effect by studying borderline personality disorder
      (BPD). Individuals with BD (n = 36), BPD (n = 22) and healthy volunteers (HC, n =
      25) wore a portable heart rate and actigraphy device and used a smart-phone to
      record self-assessed mood scores 10 times per day for 1 week. Average diurnal
      patterns of heart rate (HR), activity and sleep were compared within and across
      groups. Desynchronization in the phase of diurnal rhythms of HR compared with
      activity were found in BPD (+3 h) and BD (+1 h), but not in HC. A clear diurnal
      pattern for positive mood was found in all subject groups. The coherence between
      negative and irritable mood and HR showed a four-cycle per day component in BD
      and BPD, which was not present in HC. The findings highlight marked de
      synchronisation of measured diurnal function in both BD but particularly BPD and
      suggest an increased association with negative and irritable mood at ultradian
      frequencies. These findings enhance our understanding of the underlying
      physiological changes associated with BPD and BD, and suggest objective markers
      for monitoring and potential treatment targets. Improved mood stabilisation is a
      translational objective for management of both patient groups.

PMID- 29643340
TI  - Potential formula of the nonregular m * n fan network and its application.
AB  - Potential formula of an arbitrary resistor network has been an unsolved problem
      for hundreds of years, which is an interdisciplinary problem that involves many
      areas of natural science. A new progress has been made in this paper, which
      discovered the potential formula of a nonregular m * n fan network with two
      arbitrary boundaries by the Recursion-Transform method with potential parameters
      (simply call RT-V). The nonregular m * n fan network is a multipurpose network
      contains several different types of network model such as the interesting snail
      network and hart network. In the meantime, we discussed the semi-infinite fan
      network and a series of novel and special conclusions are produced, the effective
      resistance is educed naturally. The discovery of potential formulae of resistor
      network provides new theoretical tools and techniques for related scientific
      research.

PMID- 29643341
TI  - High power surface emitting terahertz laser with hybrid second- and fourth-order
      Bragg gratings.
AB  - A surface-emitting distributed feedback (DFB) laser with second-order gratings
      typically excites an antisymmetric mode that has low radiative efficiency and a
      double-lobed far-field beam. The radiative efficiency could be increased by using
      curved and chirped gratings for infrared diode lasers, plasmon-assisted mode
      selection for mid-infrared quantum cascade lasers (QCLs), and graded photonic
      structures for terahertz QCLs. Here, we demonstrate a new hybrid grating scheme
      that uses a superposition of second and fourth-order Bragg gratings that excite a
      symmetric mode with much greater radiative efficiency. The scheme is implemented
      for terahertz QCLs with metallic waveguides. Peak power output of 170 mW with a
      slope-efficiency of 993 mW A-1 is detected with robust single-mode single-lobed
      emission for a 3.4 THz QCL operating at 62 K. The hybrid grating scheme is
      arguably simpler to implement than aforementioned DFB schemes and could be used
      to increase power output for surface-emitting DFB lasers at any wavelength.

PMID- 29643342
TI  - The relationship between outflow resistance and trabecular meshwork stiffness in
      mice.
AB  - It has been suggested that common mechanisms may underlie the pathogenesis of
      primary open-angle glaucoma (POAG) and steroid-induced glaucoma (SIG). The
      biomechanical properties (stiffness) of the trabecular meshwork (TM) have been
      shown to differ between POAG patients and unaffected individuals. While features
      such as ocular hypertension and increased outflow resistance in POAG and SIG have
      been replicated in mouse models, whether changes of TM stiffness contributes to
      altered IOP homeostasis remains unknown. We found that outer TM was stiffer than
      the inner TM and, there was a significant positive correlation between outflow
      resistance and TM stiffness in mice where conditions are well controlled. This
      suggests that TM stiffness is intimately involved in establishing outflow
      resistance, motivating further studies to investigate factors underlying TM
      biomechanical property regulation. Such factors may play a role in the
      pathophysiology of ocular hypertension. Additionally, this finding may imply that
      manipulating TM may be a promising approach to restore normal outflow dynamics in
      glaucoma. Further, novel technologies are being developed to measure ocular
      tissue stiffness in situ. Thus, the changes of TM stiffness might be a surrogate
      marker to help in diagnosing altered conventional outflow pathway function if
      those technologies could be adapted to TM.

PMID- 29643343
TI  - Author Correction: CryoEM structure of Saccharomyces cerevisiae U1 snRNP offers
      insight into alternative splicing.
AB  - The originally published version of this Article contained several errors in
      Figure 2, panel a: the basepair register in SL3-4 of yeast U1 snRNA was depicted
      incorrectly; the basepair for A287-U295 in yeast U1 snRNA was erroneously
      present; basepairs for U84-G119, G309-U532, A288-U295 and U289-A294 in yeast U1
      snRNA were missing; the bulging nucleotide in SL3 of human U1 snRNA was depicted
      as G instead of C; and the dashed boxes defining the 5' ss binding site and Sm
      site in both human and yeast snRNAs were not drawn accurately. These have now
      been corrected in both the PDF and HTML versions of the Article.

PMID- 29643344
TI  - Bumblebee olfactory learning affected by task allocation but not by a trypanosome
      parasite.
AB  - Parasites can induce behavioural changes in their host organisms. Several
      parasite species are known to infect bumblebees, an important group of
      pollinators. Task allocation within bumblebee colonies can also cause differences
      in behaviour. Thus, task allocation may lead to context-dependent impacts of
      parasites on host behaviour. This study uses Bombus terrestris and its gut
      trypanosome Crithidia bombi, to investigate the effects of parasitism, task
      allocation (foraging or nest-work) and their interactions, on olfactory learning.
      Prior to undergoing the olfactory learning task, bees were orally infected with a
      field-realistic dose of C. bombi, and observed to determine task allocation.
      Parasitism did not significantly affect olfactory learning, but task allocation
      did, with foragers being significantly more likely to learn than nest bees. There
      was no significant interaction between parasitism and task. These results suggest
      that C. bombi is unlikely to affect pollination services via changes in olfactory
      learning of its host if bees are under no environmental or nutritional stress.
      However, wild and commercial colonies are likely to face such stressors. Future
      studies in the field are needed to extrapolate our results to real world effects.

PMID- 29643345
TI  - Fluorinated reduced graphene oxide as a protective layer on the metallic lithium
      for application in the high energy batteries.
AB  - Metallic lithium is considered to be one of the most promising anode materials
      since it offers high volumetric and gravimetric energy densities when combined
      with high-voltage or high-capacity cathodes. However, the main impediment to the
      practical applications of metallic lithium is its unstable solid electrolyte
      interface (SEI), which results in constant lithium consumption for the formation
      of fresh SEI, together with lithium dendritic growth during electrochemical
      cycling. Here we present the electrochemical performance of a fluorinated reduced
      graphene oxide interlayer (FGI) on the metallic lithium surface, tested in
      lithium symmetrical cells and in combination with two different cathode
      materials. The FGI on the metallic lithium exhibit two roles, firstly it acts as
      a Li-ion conductive layer and electronic insulator and secondly, it effectively
      suppresses the formation of high surface area lithium (HSAL). An enhanced
      electrochemical performance of the full cell battery system with two different
      types of cathodes was shown in the carbonate or in the ether based electrolytes.
      The presented results indicate a potential application in future secondary Li
      metal batteries.

PMID- 29643346
TI  - Ultrastable metallic glasses formed on cold substrates.
AB  - Vitrification from physical vapor deposition is known to be an efficient way for
      tuning the kinetic and thermodynamic stability of glasses and significantly
      improve their properties. There is a general consensus that preparing stable
      glasses requires the use of high substrate temperatures close to the glass
      transition one, Tg. Here, we challenge this empirical rule by showing the
      formation of Zr-based ultrastable metallic glasses (MGs) at room temperature,
      i.e., with a substrate temperature of only 0.43Tg. By carefully controlling the
      deposition rate, we can improve the stability of the obtained glasses to higher
      values. In contrast to conventional quenched glasses, the ultrastable MGs exhibit
      a large increase of Tg of ~60 K, stronger resistance against crystallization, and
      more homogeneous structure with less order at longer distances. Our study
      circumvents the limitation of substrate temperature for developing ultrastable
      glasses, and provides deeper insight into glasses stability and their surface
      dynamics.

PMID- 29643347
TI  - Supported black phosphorus nanosheets as hydrogen-evolving photocatalyst
      achieving 5.4% energy conversion efficiency at 353 K.
AB  - Solar-driven water splitting using powdered catalysts is considered as the most
      economical means for hydrogen generation. However, four-electron-driven oxidation
      half-reaction showing slow kinetics, accompanying with insufficient light
      absorption and rapid carrier combination in photocatalysts leads to low solar-to
      hydrogen energy conversion efficiency. Here, we report amorphous cobalt phosphide
      (Co-P)-supported black phosphorus nanosheets employed as photocatalysts can
      simultaneously address these issues. The nanosheets exhibit robust hydrogen
      evolution from pure water (pH = 6.8) without bias and hole scavengers, achieving
      an apparent quantum efficiency of 42.55% at 430 nm and energy conversion
      efficiency of over 5.4% at 353 K. This photocatalytic activity is attributed to
      extremely efficient utilization of solar energy (~75% of solar energy) by black
      phosphorus nanosheets and high-carrier separation efficiency by amorphous Co-P.
      The hybrid material design realizes efficient solar-to-chemical energy conversion
      in suspension, demonstrating the potential of black phosphorus-based materials as
      catalysts for solar hydrogen production.

PMID- 29643348
TI  - Publisher Correction: New noninvasive index for predicting liver fibrosis in
      Asian patients with chronic viral hepatitis.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 29643349
TI  - Chirality-controlled crystallization via screw dislocations.
AB  - Chirality plays an important role in science from enantiomeric separation in
      chemistry to chiral plasmonics in nanotechnology. However, the understanding of
      chirality amplification from chiral building blocks to ordered helical
      superstructures remains a challenge. Here, we demonstrate that topological
      defects, such as screw dislocations, can drive the chirality transfer from
      particle to supramolecular structure level during the crystallization process. By
      using a model system of chiral particles, which enables direct imaging of single
      particle incorporation into growing crystals, we show that the crystallization
      kinetic pathway is the key parameter for monitoring, via the defects, the
      chirality amplification of the crystalline structures from racemic to
      predominantly homohelical. We provide an explanation based on the interplay
      between geometrical frustration, racemization induced by thermal fluctuations,
      and particle chirality. Our results demonstrate that screw dislocations not only
      promote the growth, but also control the chiral morphology and therefore the
      functionality of crystalline states.

PMID- 29643350
TI  - Towards a new approach to reveal dynamical organization of the brain using
      topological data analysis.
AB  - Little is known about how our brains dynamically adapt for efficient functioning.
      Most previous work has focused on analyzing changes in co-fluctuations between a
      set of brain regions over several temporal segments of the data. We argue that by
      collapsing data in space or time, we stand to lose useful information about the
      brain's dynamical organization. Here we use Topological Data Analysis to reveal
      the overall organization of whole-brain activity maps at a single-participant
      level-as an interactive representation-without arbitrarily collapsing data in
      space or time. Using existing multitask fMRI datasets, with the known ground
      truth about the timing of transitions from one task-block to next, our approach
      tracks both within- and between-task transitions at a much faster time scale (~4
      9 s) than before. The individual differences in the revealed dynamical
      organization predict task performance. In summary, our approach distills complex
      brain dynamics into interactive and behaviorally relevant representations.

PMID- 29643352
TI  - Phylogeny, biogeography and methodology: a meta-analytic perspective on
      heterogeneity in adult marine turtle survival rates.
AB  - Comparative syntheses of key demographic parameters are critical not only for
      identifying data gaps, but also for evaluating sources of heterogeneity among
      estimates. Because demographic studies frequently exhibit heterogeneity,
      evaluating sources of heterogeneity among estimates can inform biological
      patterns and conservation actions more broadly. To better understand adult
      survival in marine turtles and avoid drawing inaccurate conclusions from current
      estimates, we conducted a comprehensive meta-analysis to test how heterogeneity
      among estimates was partitioned among phylogenetic, biogeographic and
      methodological factors. Fifty-nine studies from five marine turtle species met
      the minimum selection criteria for inclusion in our meta-analysis. Heterogeneity
      among survival estimates was first partitioned between differences in ocean basin
      (Indo-Pacific versus Atlantic), then by differences among family/tribe within the
      Indo-Pacific (Chelonini versus Carettini and Dermochelidae). However, apparent
      differences attributed to biogeography (ocean basin effect) and phylogeny
      (family/tribe effect) were highly correlated with methodological differences in
      tag type, model type, habitat type and study duration, thereby confounding
      biological interpretations and complicating efforts to use many current survival
      estimates in population assessments. Our results highlight the importance of
      evaluating sources of heterogeneity when interpreting patterns among similar
      demographic studies and directly inform efforts to identify research priorities
      for marine turtles globally.

PMID- 29643351
TI  - Synaptically silent sensory hair cells in zebrafish are recruited after damage.
AB  - Analysis of mechanotransduction among ensembles of sensory hair cells in vivo is
      challenging in many species. To overcome this challenge, we used optical
      indicators to investigate mechanotransduction among collections of hair cells in
      intact zebrafish. Our imaging reveals a previously undiscovered disconnect
      between hair-cell mechanosensation and synaptic transmission. We show that
      saturating mechanical stimuli able to open mechanically gated channels are
      unexpectedly insufficient to evoke vesicle fusion in the majority of hair cells.
      Although synaptically silent, latent hair cells can be rapidly recruited after
      damage, demonstrating that they are synaptically competent. Therefore
      synaptically silent hair cells may be an important reserve that acts to maintain
      sensory function. Our results demonstrate a previously unidentified level of
      complexity in sculpting sensory transmission from the periphery.

PMID- 29643353
TI  - Publisher Correction: Rotating robots move collectively and self-organize.
AB  - The original version of this Article contained an error in Fig. 5. In Fig. 5e,
      the scale on the y-axis originally incorrectly went from '0' to '1.10-4'. The
      correct scale goes from '0' to '0.4'. In Fig 5f, the x-axis labels were
      incorrectly shifted to the right. This has been corrected in both the PDF and
      HTML versions of the Article.

PMID- 29643354
TI  - Age-Period-Cohort Analysis of Trends in Mortality from Drowning in China: Data
      from the Global Burden of Disease Study 2015.
AB  - The studies on drowning mortality are very scarce in China, and the aim of this
      study is to identify the long-term patterns of drowning mortality in China
      between 1990 and 2015 to provide evidence for further prevention and control on
      drowning. The mortality data were derived from the Global Burden of Disease Study
      2015 and were analyzed with the age-period-cohort framework. This study
      demonstrated that the age-standardized mortality rates for drowning in both sexes
      displayed general declining trends with a decrease in the drowning mortality rate
      for every age group. In the same birth cohort, both sexes witnessed a substantial
      decline followed by a slight increase in the risk of death from drowning with age
      after controlling for period deviations. The estimated period and cohort relative
      risks were found in similar monotonic downward patterns for both sexes, with more
      reduction for females than for males during the whole study period.

PMID- 29643355
TI  - Reverse translated and gold standard continuous performance tests predict global
      cognitive performance in schizophrenia.
AB  - Attentional dysfunction contributes to functional impairments in schizophrenia
      (SZ). Sustained attention is typically assessed via continuous performance tasks
      (CPTs), though many CPTs have limited cross-species translational validity and
      place demands on additional cognitive domains. A reverse-translated 5-Choice
      Continuous Performance Task (5C-CPT) for human testing-originally developed for
      use in rodents-was designed to minimize demands on perceptual, visual learning,
      processing speed, or working memory functions. To-date, no studies have validated
      the 5C-CPT against gold standard attentional measures nor evaluated how 5C-CPT
      scores relate to cognition in SZ. Here we examined the relationship between the
      5C-CPT and the CPT-Identical Pairs (CPT-IP), an established and psychometrically
      robust measure of vigilance from the MATRICS Consensus Cognitive Battery (MCCB)
      in a sample of SZ patients (n = 35). Relationships to global and individual
      subdomains of cognition were also assessed. 5C-CPT and CPT-IP measures of
      performance (d-prime) were strongly correlated (r = 0.60). In a regression model,
      the 5C-CPT and CPT-IP collectively accounted for 54% of the total variance in
      MCCB total scores, and 27.6% of overall cognitive variance was shared between the
      5C-CPT and CPT-IP. These results indicate that the reverse translated 5C-CPT and
      the gold standard CPT-IP index a common attentional construct that also
      significantly overlaps with variance in general cognitive performance. The use of
      simple, cross-species validated behavioral indices of attentional/cognitive
      functioning such as the 5C-CPT could accelerate the development of novel
      generalized pro-cognitive therapeutics for SZ and related neuropsychiatric
      disorders.

PMID- 29643356
TI  - DISC1 regulates lactate metabolism in astrocytes: implications for psychiatric
      disorders.
AB  - Our knowledge of how genetic risk variants contribute to psychiatric disease is
      mainly limited to neurons. However, the mechanisms whereby the same genetic risk
      factors could affect the physiology of glial cells remain poorly understood. We
      studied the role of a psychiatric genetic risk factor, Disrupted-In-Schizophrenia
      1 (DISC1), in metabolic functions of astrocytes. We evaluated the effects of
      knockdown of mouse endogenous DISC1 (DISC1-KD) and expression of a dominant
      negative, C-terminus truncated human DISC1 (DN-DISC1) on the markers of energy
      metabolism, including glucose uptake and lactate production, in primary
      astrocytes and in mice with selective expression of DN-DISC1 in astrocytes. We
      also assessed the effects of lactate treatment on altered affective behaviors and
      impaired spatial memory in DN-DISC1 mice. Both DISC1-KD and DN-DISC1 comparably
      decreased mRNA and protein levels of glucose transporter 4 and glucose uptake by
      primary astrocytes. Decreased glucose uptake was associated with reduced
      oxidative phosphorylation and glycolysis as well as diminished lactate production
      in vitro and in vivo. No significant effects of DISC1 manipulations in astrocytes
      were observed on expression of the subunits of the electron transport chain
      complexes or mitofilin, a neuronal DISC1 partner. Lactate treatment rescued the
      abnormal behaviors in DN-DISC1 male and female mice. Our results suggest that
      DISC1 may be involved in the regulation of lactate production in astrocytes to
      support neuronal activity and associated behaviors. Abnormal expression of DISC1
      in astrocytes and resulting abnormalities in energy supply may be responsible for
      aspects of mood and cognitive disorders observed in patients with major
      psychiatric illnesses.

PMID- 29643357
TI  - Release of Staphylococcus aureus extracellular vesicles and their application as
      a vaccine platform.
AB  - Secretion of extracellular vesicles (EVs), a process common to eukaryotes,
      archae, and bacteria, represents a secretory pathway that allows cell-free
      intercellular communication. Microbial EVs package diverse proteins and influence
      the host-pathogen interaction, but the mechanisms underlying EV production in
      Gram-positive bacteria are poorly understood. Here we show that EVs purified from
      community-associated methicillin-resistant Staphylococcus aureus package
      cytosolic, surface, and secreted proteins, including cytolysins. Staphylococcal
      alpha-type phenol-soluble modulins promote EV biogenesis by disrupting the
      cytoplasmic membrane; whereas, peptidoglycan cross-linking and autolysin activity
      modulate EV production by altering the permeability of the cell wall. We
      demonstrate that EVs purified from a S. aureus mutant that is genetically
      engineered to express detoxified cytolysins are immunogenic in mice, elicit
      cytolysin-neutralizing antibodies, and protect the animals in a lethal sepsis
      model. Our study reveals mechanisms underlying S. aureus EV production and
      highlights the usefulness of EVs as a S. aureus vaccine platform.

PMID- 29643358
TI  - Polygenic risk for schizophrenia and measured domains of cognition in individuals
      with psychosis and controls.
AB  - Psychotic disorders including schizophrenia are commonly accompanied by cognitive
      deficits. Recent studies have reported negative genetic correlations between
      schizophrenia and indicators of cognitive ability such as general intelligence
      and processing speed. Here we compare the effect of polygenetic risk for
      schizophrenia (PRSSCZ) on measures that differ in their relationships with
      psychosis onset: a measure of current cognitive abilities (the Brief Assessment
      of Cognition in Schizophrenia, BACS) that is greatly reduced in psychotic
      disorder patients, a measure of premorbid intelligence that is minimally affected
      by psychosis onset (the Wide-Range Achievement Test, WRAT); and educational
      attainment (EY), which covaries with both BACS and WRAT. Using genome-wide single
      nucleotide polymorphism (SNP) data from 314 psychotic and 423 healthy research
      participants in the Bipolar-Schizophrenia Network for Intermediate Phenotypes (B
      SNIP) Consortium, we investigated the association of PRSSCZ with BACS, WRAT, and
      EY. Among apparently healthy individuals, greater genetic risk for schizophrenia
      (PRSSCZ) was significantly associated with lower BACS scores (r = -0.17, p = 6.6
      * 10-4 at PT = 1 * 10-4), but not with WRAT or EY. Among individuals with
      psychosis, PRSSCZ did not associate with variations in any of these three
      phenotypes. We further investigated the association between PRSSCZ and WRAT in
      more than 4500 healthy subjects from the Philadelphia Neurodevelopmental Cohort.
      The association was again null (p > 0.3, N = 4511), suggesting that different
      cognitive phenotypes vary in their etiologic relationship with schizophrenia.

PMID- 29643359
TI  - IL23 and TGF-beta diminish macrophage associated metastasis in pancreatic
      carcinoma.
AB  - The precise role of tumor associated macrophages remains unclear in pancreatic
      ductal adenocarcinoma (PDAC) while TGF-beta has an unclear role in metastases
      formation. In order to understand the role of IL23, an interleukin associated
      with macrophage polarization, we investigated IL23 in the context of TGF-beta
      expression in PDAC. We hypothesized that IL23 expression is associated with
      metastatic development and survival in PDAC. We investigated IL23 and TGF-beta
      protein expression on resected PDAC patient tumor sections who were divided into
      short-term (<12 months) survivors and long-term (>30 months) survivors. Panc-1
      cells treated with IL23, TGF-beta, macrophages, or combinations thereof, were
      orthotopically implanted into NSG mice. Patients in the long-term survivor group
      had higher IL23 protein expression (P = 0.01). IL23 expression was linearly
      correlated with TGF-beta expression in patients in the short-term survivor group
      (P = 0.038). Macrophages induce a higher rate of PDAC metastasis in the mouse
      model (P = 0.02), which is abrogated by IL23 and TGF-beta treatment (P < 0.001).
      Macrophages serve a critical role in PDAC tumor growth and metastasis. TGF-beta
      contributes to a less tumorigenic TME through regulation of macrophages.
      Macrophages increases PDAC primary tumor growth and metastases formation while
      combined IL23 and TGF-beta pre-treatment diminishes these processes.

PMID- 29643360
TI  - Ghrelin is a persistent biomarker for chronic stress exposure in adolescent rats
      and humans.
AB  - Prolonged stressor exposure in adolescence enhances the risk of developing stress
      sensitive mental illnesses, including posttraumatic stress disorder (PTSD), for
      many years following exposure cessation, but the biological underpinnings of this
      long-term vulnerability are unknown. We show that severe stressor exposure
      increased circulating levels of the hormone acyl-ghrelin in adolescent rats for
      at least 130 days and in adolescent humans for at least 4.5 years. Using a rodent
      model of longitudinal PTSD vulnerability in which rodents with a history of
      stressor exposure during adolescence display enhanced fear in response to fear
      conditioning administered weeks after stressor exposure ends, we show that
      systemic delivery of a ghrelin receptor antagonist for 4 weeks surrounding
      stressor exposure (2 weeks during and 2 weeks following) prevented stress
      enhanced fear memory. These data suggest that protracted exposure to elevated
      acyl-ghrelin levels mediates a persistent vulnerability to stress-enhanced fear
      after stressor exposure ends.

PMID- 29643361
TI  - Lithium diffusion in Li5FeO4.
AB  - The anti-fluorite type Li5FeO4 has attracted significant interest as a potential
      cathode material for Li ion batteries due to its high Li content and
      electrochemical performance. Atomic scale simulation techniques have been
      employed to study the defects and Li ion migration in Li5FeO4. The calculations
      suggest that the most favorable intrinsic defect type is calculated to be the
      cation anti-site defect, in which Li+ and Fe3+ ions exchange positions. Li
      Frenkel is also found to be lower in this material (0.85 eV/defect). Long range
      lithium diffusion paths were constructed in Li5FeO4 and it is confirmed that the
      lower migration paths are three dimensional with the lowest activation energy of
      migration at 0.45 eV. Here we show that doping by Si on the Fe site is
      energetically favourable and an efficient way to introduce a high concentration
      of lithium vacancies. The introduction of Si increases the migration energy
      barrier of Li in the vicinity of the dopant to 0.59 eV. Nevertheless, the
      introduction of Si is positive for the diffusivity as the migration energy
      barrier increase is lower less than that of the lithium Frenkel process,
      therefore the activation energy of Li diffusion.

PMID- 29643362
TI  - Eigenmode orthogonality breaking and anomalous dynamics in multimode nano
      optomechanical systems under non-reciprocal coupling.
AB  - Thermal motion of nanomechanical probes directly impacts their sensitivities to
      external forces. Its proper understanding is therefore critical for ultimate
      force sensing. Here, we investigate a vectorial force field sensor: a singly
      clamped nanowire oscillating along two quasi-frequency-degenerate transverse
      directions. Its insertion in a rotational optical force field couples its
      eigenmodes non-symmetrically, causing dramatic modifications of its mechanical
      properties. In particular, the eigenmodes lose their intrinsic orthogonality. We
      show that this circumstance is at the origin of an anomalous excess of noise and
      of a violation of the fluctuation dissipation relation. Our model, which
      quantitatively accounts for all observations, provides a novel modified version
      of the fluctuation dissipation theorem that remains valid in non-conservative
      rotational force fields, and that reveals the prominent role of non-axial
      mechanical susceptibilities. These findings help understand the intriguing
      properties of thermal fluctuations in non-reciprocally-coupled multimode systems.

PMID- 29643363
TI  - Publisher Correction: Triparental plants provide direct evidence for polyspermy
      induced polyploidy.
AB  - This Article contained errors in Fig. 3 that were brought to our attention by the
      authors during the production process but, inadvertently, were not corrected
      before publication. The tick marks on the y-axis in panels b, f, and k, and the
      median line in the box-and-whisker plot for biparental diploid plants (BP) in
      panel i were shifted downwards by up to 2 mm. This has now been corrected in both
      the PDF and HTML versions of the Article.

PMID- 29643364
TI  - PREDICTD PaRallel Epigenomics Data Imputation with Cloud-based Tensor
      Decomposition.
AB  - The Encyclopedia of DNA Elements (ENCODE) and the Roadmap Epigenomics Project
      seek to characterize the epigenome in diverse cell types using assays that
      identify, for example, genomic regions with modified histones or accessible
      chromatin. These efforts have produced thousands of datasets but cannot possibly
      measure each epigenomic factor in all cell types. To address this, we present a
      method, PaRallel Epigenomics Data Imputation with Cloud-based Tensor
      Decomposition (PREDICTD), to computationally impute missing experiments. PREDICTD
      leverages an elegant model called "tensor decomposition" to impute many
      experiments simultaneously. Compared with the current state-of-the-art method,
      ChromImpute, PREDICTD produces lower overall mean squared error, and combining
      the two methods yields further improvement. We show that PREDICTD data captures
      enhancer activity at noncoding human accelerated regions. PREDICTD provides
      reference imputed data and open-source software for investigating new cell types,
      and demonstrates the utility of tensor decomposition and cloud computing, both
      promising technologies for bioinformatics.

PMID- 29643365
TI  - Probing the strongly driven spin-boson model in a superconducting quantum
      circuit.
AB  - Quantum two-level systems interacting with the surroundings are ubiquitous in
      nature. The interaction suppresses quantum coherence and forces the system
      towards a steady state. Such dissipative processes are captured by the
      paradigmatic spin-boson model, describing a two-state particle, the "spin",
      interacting with an environment formed by harmonic oscillators. A fundamental
      question to date is to what extent intense coherent driving impacts a strongly
      dissipative system. Here we investigate experimentally and theoretically a
      superconducting qubit strongly coupled to an electromagnetic environment and
      subjected to a coherent drive. This setup realizes the driven Ohmic spin-boson
      model. We show that the drive reinforces environmental suppression of quantum
      coherence, and that a coherent-to-incoherent transition can be achieved by tuning
      the drive amplitude. An out-of-equilibrium detailed balance relation is
      demonstrated. These results advance fundamental understanding of open quantum
      systems and bear potential for the design of entangled light-matter states.

PMID- 29643366
TI  - Constant strain accumulation rate between major earthquakes on the North
      Anatolian Fault.
AB  - Earthquakes are caused by the release of tectonic strain accumulated between
      events. Recent advances in satellite geodesy mean we can now measure this
      interseismic strain accumulation with a high degree of accuracy. But it remains
      unclear how to interpret short-term geodetic observations, measured over decades,
      when estimating the seismic hazard of faults accumulating strain over centuries.
      Here, we show that strain accumulation rates calculated from geodetic
      measurements around a major transform fault are constant for its entire 250-year
      interseismic period, except in the ~10 years following an earthquake. The shear
      strain rate history requires a weak fault zone embedded within a strong lower
      crust with viscosity greater than ~1020 Pa s. The results support the notion that
      short-term geodetic observations can directly contribute to long-term seismic
      hazard assessment and suggest that lower-crustal viscosities derived from
      postseismic studies are not representative of the lower crust at all spatial and
      temporal scales.

PMID- 29643367
TI  - Author Correction: Culex pipiens crossing type diversity is governed by an
      amplified and polymorphic operon of Wolbachia.
AB  - In the originally published HTML and PDF versions of this Article, gel images in
      Figures 7c and 8c were not prepared as per the Nature journal policy. These
      figure panels have now been corrected in both the PDF and HTML versions of the
      Article.In Fig. 7c, the lane labelled 'Ha' was inappropriately duplicated to
      represent the lane labelled 'Ich13'. The corrected version of Fig. 7c includes
      PCR-RFLP on DNA from the Ichkeul 13 line, which had been run on a separate gel.
      The original unprocessed gel images are provided in Supplementary Figure 1
      associated with this correction, with the relevant corresponding bands denoted. A
      repeat experiment of the PCR-RFLP test is also presented as Supplementary Figure
      2.In Fig. 8c, the image was assembled from two separate gels without clear
      demarcation. The corrected Fig. 8c clearly separates lanes from the two gels, and
      the original unprocessed gel images are provided in the Supplementary Information
      associated with this correction.These corrections do not alter the original
      meaning of the experiments, their results, their interpretation, or the
      conclusions of the paper. We apologize for any confusion this may have caused to
      the readers of Nature Communications.

PMID- 29643368
TI  - Controlling symmetry and localization with an artificial gauge field in a
      disordered quantum system.
AB  - Anderson localization, the absence of diffusion in disordered media, draws its
      origins from the destructive interference between multiple scattering paths. The
      localization properties of disordered systems are expected to be dramatically
      sensitive to their symmetries. So far, this question has been little explored
      experimentally. Here we investigate the realization of an artificial gauge field
      in a synthetic (temporal) dimension of a disordered, periodically driven quantum
      system. Tuning the strength of this gauge field allows us to control the parity
      time symmetry properties of the system, which we probe through the experimental
      observation of three symmetry-sensitive signatures of localization. The first two
      are the coherent backscattering, marker of weak localization, and the recently
      predicted coherent forward scattering, genuine interferential signature of
      Anderson localization. The third is the direct measurement of the beta(g) scaling
      function in two different symmetry classes, allowing to demonstrate its
      universality and the one-parameter scaling hypothesis.

PMID- 29643369
TI  - Allosteric regulation alters carrier domain translocation in pyruvate
      carboxylase.
AB  - Pyruvate carboxylase (PC) catalyzes the ATP-dependent carboxylation of pyruvate
      to oxaloacetate. The reaction occurs in two separate catalytic domains, coupled
      by the long-range translocation of a biotinylated carrier domain (BCCP). Here, we
      use a series of hybrid PC enzymes to examine multiple BCCP translocation pathways
      in PC. These studies reveal that the BCCP domain of PC adopts a wide range of
      translocation pathways during catalysis. Furthermore, the allosteric activator,
      acetyl CoA, promotes one specific intermolecular carrier domain translocation
      pathway. These results provide a basis for the ordered thermodynamic state and
      the enhanced carboxyl group transfer efficiency in the presence of acetyl CoA,
      and reveal that the allosteric effector regulates enzyme activity by altering
      carrier domain movement. Given the similarities with enzymes involved in the
      modular synthesis of natural products, the allosteric regulation of carrier
      domain movements in PC is likely to be broadly applicable to multiple important
      enzyme systems.

PMID- 29643372
TI  - Good and Bad: Love and Intimacy From Plato to Melanie Klein.
AB  - Melanie Klein's theories on love outline a complex system of relations-an
      oscillating dynamic of psychical and emotional tendencies following from both
      actual experience and fantasies produced by the mind. Her insights are often
      discussed and applied in psychoanalytical contexts, but the philosophical
      implications of her theory-especially in relation to Platonic thought-have rarely
      been discussed. In this article, I will attempt to address this gap by setting
      out some preliminary yet core considerations shared by both Plato and Klein.
      First, I will describe some structural parallels between Kleinian and Platonic
      thought, especially in dialectical terms. Second, I will outline Plato's covert
      influence on Freud as passing through the teachings of philosopher Franz
      Brentano. And last, I will discuss intimacy as a struggle between the forces of
      good and bad, creativity and destruction, and love and hate-suggesting that
      Klein's conception of love emerges as a moral exigency.

PMID- 29643373
TI  - READING WILLY WONKA IN THE ERA OF ANTI-THINKING.
AB  - Whether encountered as a movie or novel, Roald Dahl's Charlie and the Chocolate
      Factory is a childhood staple of postwar Anglophone culture. Originally published
      in 1964, Dahl's story of "Willie Wonka" is a morality tale for our times
      addressed by the present essay in relation to the precariousness, violence,
      intergenerational faith, and materialist fantasies reflective of contemporary
      life in the early twenty-first century. Compensating for the precarity of
      contemporary life's impoverishment as assumptions of societal stability are
      overthrown, this chronicle of the Bucket family details: envious desire validated
      by large group chosen trauma; authoritarian enslavement of inferior, colonized
      peoples with murderous, industrial-level human experimentation; toward
      gratification of the greedy fantasy of unlimited sweetness under the sway of
      lethal identification with the aggressor.

PMID- 29643370
TI  - How single mutations affect viral escape from broad and narrow antibodies to H1
      influenza hemagglutinin.
AB  - Influenza virus can escape most antibodies with single mutations. However, rare
      antibodies broadly neutralize many viral strains. It is unclear how easily
      influenza virus might escape such antibodies if there was strong pressure to do
      so. Here, we map all single amino-acid mutations that increase resistance to
      broad antibodies to H1 hemagglutinin. Our approach not only identifies antigenic
      mutations but also quantifies their effect sizes. All antibodies select
      mutations, but the effect sizes vary widely. The virus can escape a broad
      antibody to hemagglutinin's receptor-binding site the same way it escapes narrow
      strain-specific antibodies: via single mutations with huge effects. In contrast,
      broad antibodies to hemagglutinin's stalk only select mutations with small
      effects. Therefore, among the antibodies we examine, breadth is an imperfect
      indicator of the potential for viral escape via single mutations. Antibodies
      targeting the H1 hemagglutinin stalk are quantifiably harder to escape than the
      other antibodies tested here.

PMID- 29643374
TI  - BPA exposure is associated with non-monotonic alteration in ESR1 promoter
      methylation in peripheral blood of men and shorter relative telomere length in
      peripheral blood of women.
AB  - The aim of this study was to evaluate the potential association of urinary
      Bisphenol A (BPA) levels with estrogen receptor alpha (ESR1) promoter %
      methylation and relative telomere length in a sample of 482 participants. Urinary
      BPA concentration was measured using organic phase extraction followed by high
      performance liquid chromatography mass spectroscopy. Peripheral blood ESR1
      promoter % methylation and relative telomere length were measured using direct
      bisulfite sequencing and real-time polymerase chain reaction, respectively. The
      mean +/- SD urinary BPA concentration adjusted for urinary creatinine was 2.90 +/
      4.81 (MUg/g creatinine) with a median of 1.86 MUg/g creatinine (min-max: <LOD 
      69.85). There was a potentially non-monotonic relationship between adjusted
      urinary BPA concentrations and ESR1 promoter % methylation in men. As a matter of
      fact, for the lowest tertile of ESR1 promoter % methylation, the OR and 95% CI of
      the middle and highest tertiles of urinary adjusted BPA were 2.54 (1.01-6.39) and
      1.64 (0.55-4.86) when compared to the lowest BPA tertile, respectively. After
      adjustment for potential confounders, similar results remained in men and
      appeared in the whole cohort. As for relative telomere length, there was a
      significant trend whereby higher adjusted urinary BPA concentrations were
      significantly associated with shorter relative telomere length in females. For
      instance, for the shortest relative telomere length tertile, the OR and 95% CI of
      the middle and highest tertiles of urinary adjusted BPA were 2.91 (1.38-6.16) and
      3.19 (1.57-6.49) when compared to the lowest BPA tertile, respectively. This
      trend remained significant after adjustment for potential confounders.

PMID- 29643375
TI  - Conditional privatization of a public siderophore enables Pseudomonas aeruginosa
      to resist cheater invasion.
AB  - Understanding the mechanisms that promote cooperative behaviors of bacteria in
      their hosts is of great significance to clinical therapies. Environmental stress
      is generally believed to increase competition and reduce cooperation in bacteria.
      Here, we show that bacterial cooperation can in fact be maintained because of
      environmental stress. We show that Pseudomonas aeruginosa regulates the secretion
      of iron-scavenging siderophores in the presence of different environmental
      stresses, reserving this public good for private use in protection against
      reactive oxygen species when under stress. We term this strategy "conditional
      privatization". Using a combination of experimental evolution and theoretical
      modeling, we demonstrate that in the presence of environmental stress the
      conditional privatization strategy is resistant to invasion by non-producing
      cheaters. These findings show how the regulation of public goods secretion under
      stress affects the evolutionary stability of cooperation in a pathogenic
      population, which may assist in the rational development of novel therapies.

PMID- 29643376
TI  - Host-mediated selection impacts the diversity of Plasmodium falciparum antigens
      within infections.
AB  - Host immunity exerts strong selective pressure on pathogens. Population-level
      genetic analysis can identify signatures of this selection, but these signatures
      reflect the net selective effect of all hosts and vectors in a population. In
      contrast, analysis of pathogen diversity within hosts provides information on
      individual, host-specific selection pressures. Here, we combine these
      complementary approaches in an analysis of the malaria parasite Plasmodium
      falciparum using haplotype sequences from thousands of natural infections in sub
      Saharan Africa. We find that parasite genotypes show preferential clustering
      within multi-strain infections in young children, and identify individual amino
      acid positions that may contribute to strain-specific immunity. Our results
      demonstrate that natural host defenses to P. falciparum act in an allele-specific
      manner to block specific parasite haplotypes from establishing blood-stage
      infections. This selection partially explains the extreme amino acid diversity of
      many parasite antigens and suggests that vaccines targeting such proteins should
      account for allele-specific immunity.

PMID- 29643378
TI  - The value of radial endobronchial ultrasound-guided bronchial brushing in
      peripheral non-squamous non-small cell lung cancer.
AB  - Radial endobronchial ultrasound (R-EBUS) is one important diagnostic approach in
      non-small cell lung cancers (NSCLC). However, the small samples obtained from R
      EBUS-guided transbronchial biopsies are sometimes insufficient for pathological
      and molecular diagnosis. Herein, we investigated the suitability of R-EBUS-guided
      bronchial brushing specimens for NSCLC diagnosis and EGFR genotyping. We enrolled
      941 consecutive patients with peripheral pulmonary lesions who underwent R-EBUS.
      Cytology-positive brushing specimens from non-squamous NSCLC patients were tested
      for EGFR mutations. Non-squamous NSCLC was diagnosed in 624 patients (66.3%).
      Positive cytology was documented in the brushing samples of 376 patients (60.3%).
      Higher diagnostic yields were obtained in patients exhibiting bronchus signs on
      chest tomography, and those with R-EBUS probe located within the lesion. EGFR
      genotyping was successfully performed in 363 samples (96.5% of cytology-positive
      brushing samples). EGFR genotyping concordance between brushing specimens and
      matched tissue samples was 88.7% (kappa = 0.745, P < 0.001). Furthermore, 144 non
      squamous NSCLC patients (23.1%) with failed pathological diagnosis or EGER
      sequencing by R-EBUS-guided transbronchial biopsy required repeat biopsies.
      However, it was achieved successfully from the brushing specimens of 57 patients
      (39.6%). In conclusion, for patients with peripheral lung cancer, R-EBUS-guided
      bronchial brushing could provide an additional sampling method for diagnosis and
      EGFR genotyping.

PMID- 29643379
TI  - Publisher Correction: Role of Dopamine D2 Receptor in Stress-Induced Myelin Loss.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 29643377
TI  - Molecular basis for the folding of beta-helical autotransporter passenger
      domains.
AB  - Bacterial autotransporters comprise a C-terminal beta-barrel domain, which must
      be correctly folded and inserted into the outer membrane to facilitate
      translocation of the N-terminal passenger domain to the cell exterior. Once at
      the surface, the passenger domains of most autotransporters are folded into an
      elongated beta-helix. In a cellular context, key molecules catalyze the assembly
      of the autotransporter beta-barrel domain. However, how the passenger domain
      folds into its functional form is poorly understood. Here we use mutational
      analysis on the autotransporter Pet to show that the beta-hairpin structure of
      the fifth extracellular loop of the beta-barrel domain has a crucial role for
      passenger domain folding into a beta-helix. Bioinformatics and structural
      analyses, and mutagenesis of a homologous autotransporter, suggest that this
      function is conserved among autotransporter proteins with beta-helical passenger
      domains. We propose that the autotransporter beta-barrel domain is a folding
      vector that nucleates folding of the passenger domain.

PMID- 29643380
TI  - Author Correction: Birds and beans: Comparing avian richness and endemism in
      arabica and robusta agroforests in India's Western Ghats.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 29643382
TI  - Snap evaporation of droplets on smooth topographies.
AB  - Droplet evaporation on solid surfaces is important in many applications including
      printing, micro-patterning and cooling. While seemingly simple, the configuration
      of evaporating droplets on solids is difficult to predict and control. This is
      because evaporation typically proceeds as a "stick-slip" sequence-a combination
      of pinning and de-pinning events dominated by static friction or "pinning",
      caused by microscopic surface roughness. Here we show how smooth, pinning-free,
      solid surfaces of non-planar topography promote a different process called snap
      evaporation. During snap evaporation a droplet follows a reproducible sequence of
      configurations, consisting of a quasi-static phase-change controlled by mass
      diffusion interrupted by out-of-equilibrium snaps. Snaps are triggered by
      bifurcations of the equilibrium droplet shape mediated by the underlying non
      planar solid. Because the evolution of droplets during snap evaporation is
      controlled by a smooth topography, and not by surface roughness, our ideas can
      inspire programmable surfaces that manage liquids in heat- and mass-transfer
      applications.

PMID- 29643381
TI  - Pannexin 1 sustains the electrophysiological responsiveness of retinal ganglion
      cells.
AB  - Pannexin 1 (Panx1) forms ATP-permeable membrane channels that play a key role in
      purinergic signaling in the nervous system in both normal and pathological
      conditions. In the retina, particularly high levels of Panx1 are found in retinal
      ganglion cells (RGCs), but the normal physiological function in these cells
      remains unclear. In this study, we used patch clamp recordings in the intact
      inner retina to show that evoked currents characteristic of Panx1 channel
      activity were detected only in RGCs, particularly in the OFF-type cells. The
      analysis of pattern electroretinogram (PERG) recordings indicated that Panx1
      contributes to the electrical output of the retina. Consistently, PERG amplitudes
      were significantly impaired in the eyes with targeted ablation of the Panx1 gene
      in RGCs. Under ocular hypertension and ischemic conditions, however, high Panx1
      activity permeated cell membranes and facilitated the selective loss of RGCs or
      stably transfected Neuro2A cells. Our results show that high expression of the
      Panx1 channel in RGCs is essential for visual function in the inner retina but
      makes these cells highly sensitive to mechanical and ischemic stresses. These
      findings are relevant to the pathophysiology of retinal disorders induced by
      increased intraocular pressure, such as glaucoma.

PMID- 29643383
TI  - A fully reconfigurable waveguide Bragg grating for programmable photonic signal
      processing.
AB  - Since the discovery of the Bragg's law in 1913, Bragg gratings have become
      important optical devices and have been extensively used in various systems. In
      particular, the successful inscription of a Bragg grating in a fiber core has
      significantly boosted its engineering applications. However, a conventional
      grating device is usually designed for a particular use, which limits general
      purpose applications since its index modulation profile is fixed after
      fabrication. In this article, we propose to implement a fully reconfigurable
      grating, which is fast and electrically reconfigurable by field programming. The
      concept is verified by fabricating an integrated grating on a silicon-on
      insulator platform, which is employed as a programmable signal processor to
      perform multiple signal processing functions including temporal differentiation,
      microwave time delay, and frequency identification. The availability of ultrafast
      and reconfigurable gratings opens new avenues for programmable optical signal
      processing at the speed of light.

PMID- 29643384
TI  - Author Correction: Seasonal total methane depletion in limestone caves.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 29643385
TI  - Inhibition of cancer stem cell like cells by a synthetic retinoid.
AB  - Developing novel drugs that can abrogate the growth and metastasis of malignant
      tumors is a major challenge for cancer researchers. Here we describe a novel
      synthetic retinoid, namely WYC-209, which inhibits proliferation of malignant
      murine melanoma tumor-repopulating cells (TRCs), known to resist conventional
      drug treatment, with an IC50 of 0.19 MUM in a dose-dependent manner. WYC-209 also
      inhibits proliferation of TRCs of human melanoma, lung cancer, ovarian cancer,
      and breast cancer in culture. Interestingly, the treated TRCs fail to resume
      growth even after the drug washout. Importantly, the molecule abrogates 87.5% of
      lung metastases of melanoma TRCs in immune-competent wild-type C57BL/6 mice at
      0.22 mg kg-1 without showing apparent toxicity. Pretreating the melanoma TRCs
      with retinoic acid receptor (RAR) antagonists or with RAR siRNAs blocks or
      reduces the inhibitory effect of the molecule, suggesting that the target of the
      molecule is RAR. WYC-209 induces TRC apoptosis and pretreating the TRCs with
      caspase 3 inhibitor or depleting caspase 3 with siRNAs substantially rescues
      growth of TRCs from WYC-209 inhibition, suggesting that WYC-209 induces TRCs
      apoptosis primarily via the caspase 3 pathway. Our findings demonstrate the
      promise of the new retinoid WYC-209 in treating malignant melanoma tumors with
      high efficacy and little toxicity.

PMID- 29643387
TI  - Computer-aided discovery of a metal-organic framework with superior oxygen
      uptake.
AB  - Current advances in materials science have resulted in the rapid emergence of
      thousands of functional adsorbent materials in recent years. This clearly creates
      multiple opportunities for their potential application, but it also creates the
      following challenge: how does one identify the most promising structures, among
      the thousands of possibilities, for a particular application? Here, we present a
      case of computer-aided material discovery, in which we complete the full cycle
      from computational screening of metal-organic framework materials for oxygen
      storage, to identification, synthesis and measurement of oxygen adsorption in the
      top-ranked structure. We introduce an interactive visualization concept to
      analyze over 1000 unique structure-property plots in five dimensions and delimit
      the relationships between structural properties and oxygen adsorption performance
      at different pressures for 2932 already-synthesized structures. We also report a
      world-record holding material for oxygen storage, UMCM-152, which delivers 22.5%
      more oxygen than the best known material to date, to the best of our knowledge.

PMID- 29643386
TI  - Somatic activating mutations in MAP2K1 cause melorheostosis.
AB  - Melorheostosis is a sporadic disease of uncertain etiology characterized by
      asymmetric bone overgrowth and functional impairment. Using whole exome
      sequencing, we identify somatic mosaic MAP2K1 mutations in affected, but not
      unaffected, bone of eight unrelated patients with melorheostosis. The activating
      mutations (Q56P, K57E and K57N) cluster tightly in the MEK1 negative regulatory
      domain. Affected bone displays a mosaic pattern of increased p-ERK1/2 in
      osteoblast immunohistochemistry. Osteoblasts cultured from affected bone comprise
      two populations with distinct p-ERK1/2 levels by flow cytometry, enhanced ERK1/2
      activation, and increased cell proliferation. However, these MAP2K1 mutations
      inhibit BMP2-mediated osteoblast mineralization and differentiation in vitro,
      underlying the markedly increased osteoid detected in affected bone histology.
      Mosaicism is also detected in the skin overlying bone lesions in four of five
      patients tested. Our data show that the MAP2K1 oncogene is important in human
      bone formation and implicate MEK1 inhibition as a potential treatment avenue for
      melorheostosis.

PMID- 29643388
TI  - Author Correction: Direct and convenient measurement of plasmid stability in lab
      and clinical isolates of E. coli.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 29643391
TI  - Author Correction: Watt-level 10-gigahertz solid-state laser enabled by self
      defocusing nonlinearities in an aperiodically poled crystal.
AB  - The original version of this Article contained an error in Fig. 3a, in which the
      delay axis was incorrectly labeled in increments of 0.5 ps instead of the correct
      0.2 ps. This has been corrected in both the PDF and HTML versions of the Article.

PMID- 29643389
TI  - Histone H3.3 sub-variant H3mm7 is required for normal skeletal muscle
      regeneration.
AB  - Regulation of gene expression requires selective incorporation of histone H3
      variant H3.3 into chromatin. Histone H3.3 has several subsidiary variants but
      their functions are unclear. Here we characterize the function of histone H3.3
      sub-variant, H3mm7, which is expressed in skeletal muscle satellite cells. H3mm7
      knockout mice demonstrate an essential role of H3mm7 in skeletal muscle
      regeneration. Chromatin analysis reveals that H3mm7 facilitates transcription by
      forming an open chromatin structure around promoter regions including those of
      myogenic genes. The crystal structure of the nucleosome containing H3mm7 reveals
      that, unlike the S57 residue of other H3 proteins, the H3mm7-specific A57 residue
      cannot form a hydrogen bond with the R40 residue of the cognate H4 molecule.
      Consequently, the H3mm7 nucleosome is unstable in vitro and exhibited higher
      mobility in vivo compared with the H3.3 nucleosome. We conclude that the unstable
      H3mm7 nucleosome may be required for proper skeletal muscle differentiation.

PMID- 29643390
TI  - Functional crosstalk between histone H2B ubiquitylation and H2A modifications and
      variants.
AB  - Ubiquitylation of histone H2B at lysine residue 120 (H2BK120ub) is a prominent
      histone posttranslational modification (PTM) associated with the actively
      transcribed genome. Although H2BK120ub triggers several critical downstream
      histone modification pathways and changes in chromatin structure, less is known
      about the regulation of the ubiquitylation reaction itself, in particular with
      respect to the modification status of the chromatin substrate. Here we employ an
      unbiased library screening approach to profile the impact of pre-existing
      chromatin modifications on de novo ubiquitylation of H2BK120 by the cognate human
      E2:E3 ligase pair, UBE2A:RNF20/40. Deposition of H2BK120ub is found to be highly
      sensitive to PTMs on the N-terminal tail of histone H2A, a crosstalk that extends
      to the common histone variant H2A.Z. Based on a series of biochemical and cell
      based studies, we propose that this crosstalk contributes to the spatial
      organization of H2BK120ub on gene bodies, and is thus important for
      transcriptional regulation.

PMID- 29643392
TI  - Author Correction: A replication study of genetic risk loci for ischemic stroke
      in a Dutch population: a case-control study.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 29643393
TI  - On the wrong track: ocean acidification attracts larval fish to irrelevant
      environmental cues.
AB  - Population replenishment of marine life largely depends on successful dispersal
      of larvae to suitable adult habitat. Ocean acidification alters behavioural
      responses to physical and chemical cues in marine animals, including the
      maladaptive deterrence of settlement-stage larval fish to odours of preferred
      habitat and attraction to odours of non-preferred habitat. However, sensory
      compensation may allow fish to use alternative settlement cues such as sound. We
      show that future ocean acidification reverses the attraction of larval fish
      (barramundi) to their preferred settlement sounds (tropical estuarine mangroves).
      Instead, acidification instigates an attraction to unfamiliar sounds (temperate
      rocky reefs) as well as artificially generated sounds (white noise), both of
      which were ignored by fish living in current day conditions. This finding
      suggests that by the end of the century, following a business as usual CO2
      emission scenario, these animals might avoid functional environmental cues and
      become attracted to cues that provide no adaptive advantage or are potentially
      deleterious. This maladaptation could disrupt population replenishment of this
      and other economically important species if animals fail to adapt to elevated CO2
      conditions.

PMID- 29643394
TI  - Author Correction: Kanglaite sensitizes colorectal cancer cells to Taxol via NF
      kappaBeta inhibition and connexin 43 upregulation.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 29643396
TI  - Effects of muscle relaxants on ischaemia damage in skeletal muscle.
AB  - Muscle ischaemia is frequently induced intraoperatively by i.e. a surgical
      tourniquet or during the re-grafting phase of a free muscle transplant. The
      resulting muscle cell damage may impact on postoperative recovery. Neuromuscular
      paralysis may mitigate the effects of ischaemia. After ethics approval, 25 male
      Sprague-Dawley rats were anaesthetized and randomly assigned to 1 of 4 groups:
      Sham operation, treatment with normal saline, treatment with rocuronium (muscle
      relaxant) 0.6 or 1 mg kg-1, respectively. In the non-sham groups, ischaemia of
      one hind leg was achieved by ligation of the femoral vessels. Muscle biopsies
      were taken at 30 and 90 min, respectively. Cell damage was assessed in the
      biopsies via the expression of dystrophin, free calcium, as well as the
      assessment of cell viability. Pre-ischaemia muscle relaxation led to a reduction
      in ischaemia-induced muscle cell damage when measured by the expression of
      dystrophin, cell viability and the expression of free calcium even after 90 min
      of ischaemia (i.e. ratio control/ischaemic site for dystrophin expression after
      saline 0.58 +/- 0.12 vs. after 1 mg/kg rocuronium 1.08 +/- 0.29; P < 0.05).
      Muscle relaxation decreased the degree of ischaemia-induced muscle cell damage.
      The results may have significant clinical implications.

PMID- 29643395
TI  - Low-intensity repetitive transcranial magnetic stimulation requires concurrent
      visual system activity to modulate visual evoked potentials in adult mice.
AB  - Repetitive transcranial stimulation (rTMS) is an increasingly popular method to
      non-invasively modulate cortical excitability in research and clinical settings.
      During rTMS, low-intensity magnetic fields reach areas perifocal to the target
      brain region, however, effects of these low-intensity (LI-) fields and how they
      interact with ongoing neural activity remains poorly defined. We evaluated
      whether coordinated neural activity during electromagnetic stimulation alters LI
      rTMS effects on cortical excitability by comparing visually evoked potentials
      (VEP) and densities of parvalbumin-expressing (PV+) GABAergic interneurons in
      adult mouse visual cortex after LI-rTMS under different conditions: LI-rTMS
      applied during visually evoked (strong, coordinated) activity or in darkness
      (weak, spontaneous activity).We also compared response to LI-rTMS in wildtype and
      ephrin-A2A5-/- mice, which have visuotopic anomalies thought to disrupt coherence
      of visually-evoked cortical activity. Demonstrating that LI-rTMS effects in V1
      require concurrent sensory-evoked activity, LI-rTMS delivered during visually
      evoked activity increased PV+ immunoreactivity in both genotypes; however, VEP
      peak amplitudes changed only in wildtypes, consistent with intracortical
      disinhibition. We show, for the first time, that neural activity and the degree
      of coordination in cortical population activity interact with LI-rTMS to alter
      excitability in a context-dependent manner.

PMID- 29643397
TI  - De novo assembly and analysis of the Artemisia argyi transcriptome and
      identification of genes involved in terpenoid biosynthesis.
AB  - Artemisia argyi Lev. et Vant. (A. argyi) is widely utilized for moxibustion in
      Chinese medicine, and the mechanism underlying terpenoid biosynthesis in its
      leaves is suggested to play an important role in its medicinal use. However, the
      A. argyi transcriptome has not been sequenced. Herein, we performed RNA
      sequencing for A. argyi leaf, root and stem tissues to identify as many as
      possible of the transcribed genes. In total, 99,807 unigenes were assembled by
      analysing the expression profiles generated from the three tissue types, and
      67,446 of those unigenes were annotated in public databases. We further performed
      differential gene expression analysis to compare leaf tissue with the other two
      tissue types and identified numerous genes that were specifically expressed or up
      regulated in leaf tissue. Specifically, we identified multiple genes encoding
      significant enzymes or transcription factors related to terpenoid synthesis. This
      study serves as a valuable resource for transcriptome information, as many
      transcribed genes related to terpenoid biosynthesis were identified in the A.
      argyi transcriptome, providing a functional genomic basis for additional studies
      on molecular mechanisms underlying the medicinal use of A. argyi.

PMID- 29643398
TI  - Deciphering the dark proteome of Chikungunya virus.
AB  - Chikungunya virus (CHIKV) is a mosquito-borne alphavirus. The outbreak of CHIKV
      infection has been seen in many tropical and subtropical regions of the
      biosphere. Current reports evidenced that after outbreaks in 2005-06, the fitness
      of this virus propagating in Aedes albopictus enhanced due to the epistatic
      mutational changes in its envelope protein. In our study, we evaluated the
      prevalence of intrinsically disordered proteins (IDPs) and IDP regions (IDPRs) in
      CHIKV proteome. IDPs/IDPRs are known as members of a 'Dark Proteome' that defined
      as a set of polypeptide segments or whole protein without unique three
      dimensional structure within the cellular milieu but with significant biological
      functions, such as cell cycle regulation, control of signaling pathways, and
      maintenance of viral proteomes. However, the intrinsically disordered aspects of
      CHIKV proteome and roles of IDPs/IDPRs in the pathogenic mechanism of this
      important virus have not been evaluated as of yet. There are no existing reports
      on the analysis of intrinsic disorder status of CHIKV. To fulfil this goal, we
      have analyzed the abundance and functionality of IDPs/IDPRs in CHIKV proteins,
      involved in the replication and maturation. It is likely that these IDPs/IDPRs
      can serve as novel targets for disorder based drug design.

PMID- 29643399
TI  - The role of stabilizing and communicating symptoms given overlapping communities
      in psychopathology networks.
AB  - Network theory, as a theoretical and methodological framework, is energizing many
      research fields, among which clinical psychology and psychiatry. Fundamental to
      the network theory of psychopathology is the role of specific symptoms and their
      interactions. Current statistical tools, however, fail to fully capture this
      constitutional property. We propose community detection tools as a means to
      evaluate the complex network structure of psychopathology, free from its original
      boundaries of distinct disorders. Unique to this approach is that symptoms can
      belong to multiple communities. Using a large community sample and spanning a
      broad range of symptoms (Symptom Checklist-90-Revised), we identified 18
      communities of interconnected symptoms. The differential role of symptoms within
      and between communities offers a framework to study the clinical concepts of
      comorbidity, heterogeneity and hallmark symptoms. Symptoms with many and strong
      connections within a community, defined as stabilizing symptoms, could be thought
      of as the core of a community, whereas symptoms that belong to multiple
      communities, defined as communicating symptoms, facilitate the communication
      between problem areas. We propose that defining symptoms on their stabilizing
      and/or communicating role within and across communities accelerates our
      understanding of these clinical phenomena, central to research and treatment of
      psychopathology.

PMID- 29643400
TI  - A Novel Lubricant Based on Covalent Functionalized Graphene Oxide Quantum Dots.
AB  - Dodecyl amine edge functionalized few-layer graphene oxide quantum dots were
      synthesized in good yields. The covalent functionalization was demonstrated with
      NMR and AFM-IR. The resulting structure and particle size was measured with AFM
      and HRTEM. The thermal stability of the compound was investigated and showed a
      stability of up to 220  degrees C. The modified graphene oxide quantum dots
      showed excellent solubility in various organic solvents, including ethers,
      methanol, toluene, n-hexane, heptane, xylene, dichloromethane and toluene. The
      stability of a resulting toluene solution was also proven by static light
      scattering measurements over several days. The excellent solubility gives the
      possibility of an efficient and fast spray application of the functionalized
      graphene oxide quantum dots to steel surfaces. Hence, the macroscopic friction
      behavior was investigated with a Thwing-Albert FP-2250 friction tester. A thin
      film of the dodecyl amine functionalized graphene oxide quantum dots on steel
      lowered the friction coefficient from 0.17 to 0.11 and revealed a significant
      corrosion inhibition effect.

PMID- 29643401
TI  - Author Correction: Aberrant methylated key genes of methyl group metabolism
      within the molecular etiology of urothelial carcinogenesis.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 29643402
TI  - Spatial Encoding of Translational Optic Flow in Planar Scenes by Elementary
      Motion Detector Arrays.
AB  - Elementary Motion Detectors (EMD) are well-established models of visual motion
      estimation in insects. The response of EMDs are tuned to specific temporal and
      spatial frequencies of the input stimuli, which matches the behavioural response
      of insects to wide-field image rotation, called the optomotor response. However,
      other behaviours, such as speed and position control, cannot be fully accounted
      for by EMDs because these behaviours are largely unaffected by image properties
      and appear to be controlled by the ratio between the flight speed and the
      distance to an object, defined here as relative nearness. We present a method
      that resolves this inconsistency by extracting an unambiguous estimate of
      relative nearness from the output of an EMD array. Our method is suitable for
      estimation of relative nearness in planar scenes such as when flying above the
      ground or beside large flat objects. We demonstrate closed loop control of the
      lateral position and forward velocity of a simulated agent flying in a corridor.
      This finding may explain how insects can measure relative nearness and control
      their flight despite the frequency tuning of EMDs. Our method also provides
      engineers with a relative nearness estimation technique that benefits from the
      low computational cost of EMDs.

PMID- 29643403
TI  - Toxicity of enrofloxacin, copper and their interactions on soil microbial
      populations and ammonia-oxidizing archaea and bacteria.
AB  - Enrofloxacin (EFX) is one of the most frequently used broad-spectrum veterinary
      drugs, and copper (Cu) is a heavy metal that could easily bind to certain
      antibiotic molecules. Hence EFX and Cu were chosen as representatives of
      antibiotics and heavy metals to explore the abundance and variation of soil
      microbial populations with a plate-counting technique, as well as the copy
      numbers of amoA gene in ammonia-oxidizing archaea (AOA) and ammonia-oxidizing
      bacteria (AOB) by quantitative PCR methods in Argosols samples. Treatments of
      applied EFX (0.05, 0.20, 0.80 mmol/kg), Cu (1.60 mmol/kg) and combined EFX and Cu
      (at molar ratios of 1:32,1:8,1:2) exhibited various effects on different soil
      microorganisms. The toxicity of combined EFX and Cu was more strongly expressed
      on both soil microbial populations and amoA gene (AOA and AOB) compared to the
      EFX treatment alone, in most cases, time and dose effects were observed. With
      respect to the amoA gene, the AOA-amoA gene was more abundant than the AOB-amoA
      gene, and the ratio ranged from ~8 to ~11. Moreover, the interaction types of EFX
      and Cu were more likely to be antagonistic (64.29%) than synergistic (35.71%) on
      soil abundance and function, which may be related to the incubation time and the
      ratio of EFX to Cu in the soil.

PMID- 29643406
TI  - Author Correction: House dust mite induced allergic airway disease is attenuated
      in CD11ccreIL-4Ralpha-/l degrees x mice.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 29643405
TI  - Author Correction: The genetic prehistory of the Baltic Sea region.
AB  - The original version of this Article omitted references to previous work, which
      are detailed in the associated Author Correction. These omissions have been
      corrected in both the PDF and HTML versions of the Article.

PMID- 29643404
TI  - Canine NAPEPLD-associated models of human myelin disorders.
AB  - Canine leukoencephalomyelopathy (LEMP) is a juvenile-onset neurodegenerative
      disorder of the CNS white matter currently described in Rottweiler and Leonberger
      dogs. Genome-wide association study (GWAS) allowed us to map LEMP in a Leonberger
      cohort to dog chromosome 18. Subsequent whole genome re-sequencing of a
      Leonberger case enabled the identification of a single private homozygous non
      synonymous missense variant located in the highly conserved metallo-beta
      lactamase domain of the N-acyl phosphatidylethanolamine phospholipase D (NAPEPLD)
      gene, encoding an enzyme of the endocannabinoid system. We then sequenced this
      gene in LEMP-affected Rottweilers and identified a different frameshift variant,
      which is predicted to replace the C-terminal metallo-beta-lactamase domain of the
      wild type protein. Haplotype analysis of SNP array genotypes revealed that the
      frameshift variant was present in diverse haplotypes in Rottweilers, and also in
      Great Danes, indicating an old origin of this second NAPEPLD variant. The
      identification of different NAPEPLD variants in dog breeds affected by
      leukoencephalopathies with heterogeneous pathological features, implicates the
      NAPEPLD enzyme as important in myelin homeostasis, and suggests a novel candidate
      gene for myelination disorders in people.

PMID- 29643407
TI  - A Highly Efficient Adsorbent Cu-Perusian Blue@Nanodiamond for Cesium in Diluted
      Artificial Seawater and Soil-Treated Wastewater.
AB  - A new adsorbent Cu-Perussian blue@Nanodiamond (Cu-PB@DND) for Cs+ removal was
      prepared and characterized with IR, SEM, X-ray diffraction, particle size
      analysis, and zeta-potential. The adsorbent consists of a core of aggregated
      detonation nanodiamond (DND) particles with the surface treated with Cu-PB.
      Cesium adsorption was studied in two modes; a co-precipitation mode and a batch
      mode. In the co-precipitation mode, DND, CuCl2, and K4[Fe(CN)6] were added
      sequentially to a Cs+ solution in diluted artificial seawater. In the batch mode,
      adsorbent Cu-PB@DND was dispersed into a Cs+ solution with stirring. The
      distribution coefficient (Kd) of the co-precipitation mode was 8.8 * 107 (mL/g)
      at Cs+ 6.6 ppm in 0.07% seawater. The Kd value of the batch mode was 1.3 * 106
      (mL/g). Precipitation of Cs+-incorporated particles was complete, and post
      filtration was not necessary. Excess copper and iron ions were completely removed
      and were not detected in the supernatant. The adsorption data for Cu-PB@DND were
      analyzed by assuming Langmuir isotherm and a good fit was obtained with a maximum
      adsorption capacity Qmax of 759 mg/g. The co-precipitation method was also
      applied to soil-treated wastewater.

PMID- 29643408
TI  - Author Correction: FUT2 non-secretor status is associated with altered
      susceptibility to symptomatic enterotoxigenic Escherichia coli infection in
      Bangladeshis.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 29643409
TI  - Intrinsically-disordered N-termini in human parechovirus 1 capsid proteins bind
      encapsidated RNA.
AB  - Human parechoviruses (HPeV) are picornaviruses with a highly-ordered RNA genome
      contained within icosahedrally-symmetric capsids. Ordered RNA structures have
      recently been shown to interact with capsid proteins VP1 and VP3 and facilitate
      virus assembly in HPeV1. Using an assay that combines reversible cross-linking,
      RNA affinity purification and peptide mass fingerprinting (RCAP), we mapped the
      RNA-interacting regions of the capsid proteins from the whole HPeV1 virion in
      solution. The intrinsically-disordered N-termini of capsid proteins VP1 and VP3,
      and unexpectedly, VP0, were identified to interact with RNA. Comparing these
      results to those obtained using recombinantly-expressed VP0 and VP1 confirmed the
      virion binding regions, and revealed unique RNA binding regions in the isolated
      VP0 not previously observed in the crystal structure of HPeV1. We used RNA
      fluorescence anisotropy to confirm the RNA-binding competency of each of the
      capsid proteins' N-termini. These findings suggests that dynamic interactions
      between the viral RNA and the capsid proteins modulate virus assembly, and
      suggest a novel role for VP0.

PMID- 29643410
TI  - Publisher Correction: Identification of microRNAs as potential cellular monocytic
      biomarkers in the early phase of myocardial infarction: a pilot study.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 29643411
TI  - Sorbent Film-Coated Passive Samplers for Explosives Vapour Detection Part B:
      Deployment in Semi-Operational Environments and Alternative Applications.
AB  - The application of new sorbent-film coated passive samplers for capture of bulk
      commercial and military explosives vapours in operationally relevant spaces such
      as luggage, rooms, vehicles and shipping containers is presented. Samplers were
      easily integrated with in-service detection technologies with little/no sample
      preparation required. Ethylene glycol dinitrate (EGDN) was detected within 4 h in
      a container holding a suitcase packed with 0.2 kg Perunit 28E. Within a 22,000
      dm3 room, 1 kg of concealed Seguridad was detected within 24 h and in an
      adjoining room within 7 days. Exposed samplers also successfully captured
      components of 1 kg TNT after 72 h and 1 kg concealed Perunit 28E after 6 h in
      both a furnished room and a large, partially filled shipping container. For the
      latter, samplers captured detectable residues outside the container after 24 h
      and were stable during wet weather for 72 h. A one-week trial at three
      operationally relevant venues including a university, a theatre and a government
      building revealed a nuisance positive rate of <1.4% (n = 72). Finally, two
      alternative applications are presented for extraction of liquid samples and use a
      particulate contact swab showing flexibility for a range of different search
      activities.

PMID- 29643412
TI  - Author Correction: First Ornithomimid (Theropoda, Ornithomimosauria) from the
      Upper Cretaceous Djadokhta Formation of Togrogiin Shiree, Mongolia.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 29643413
TI  - Nucleosomes of polyploid trophoblast giant cells mostly consist of histone
      variants and form a loose chromatin structure.
AB  - Trophoblast giant cells (TGCs) are one of the cell types that form the placenta
      and play multiple essential roles in maintaining pregnancy in rodents. TGCs have
      large, polyploid nuclei resulting from endoreduplication. While previous studies
      have shown distinct gene expression profiles of TGCs, their chromatin structure
      remains largely unknown. An appropriate combination of canonical and non
      canonical histones, also known as histone variants, allows each cell to exert its
      cell type-specific functions. Here, we aimed to reveal the dynamics of histone
      usage and chromatin structure during the differentiation of trophoblast stem
      cells (TSCs) into TGCs. Although the expression of most genes encoding canonical
      histones was downregulated, the expression of a few genes encoding histone
      variants such as H2AX, H2AZ, and H3.3 was maintained at a relatively high level
      in TGCs. Both the micrococcal nuclease digestion assay and nucleosome stability
      assay using a microfluidic device indicated that chromatin became increasingly
      loose as TSCs differentiated. Combinatorial experiments involving H3.3-knockdown
      and -overexpression demonstrated that variant H3.3 resulted in the formation of
      loose nucleosomes in TGCs. In conclusion, our study revealed that TGCs possessed
      loose nucleosomes owing to alterations in their histone composition during
      differentiation.

PMID- 29643414
TI  - Switching between individual and collective motility in B lymphocytes is
      controlled by cell-matrix adhesion and inter-cellular interactions.
AB  - Lymphocytes alternate between phases of individual migration across tissues and
      phases of clustering during activation and function. The range of lymphocyte
      motility behaviors and the identity of the factors that govern them remain
      elusive. To explore this point, we here collected unprecedented statistics
      pertaining to cell displacements, cell:matrix and cell:cell interactions using a
      model B cell line as well as primary human B lymphocytes. At low cell density,
      individual B lymphocytes displayed a high heterogeneity in their speed and
      diffusivity. Beyond this intrinsic variability, B lymphocytes adapted their
      motility to the composition of extra-cellular matrix, adopting slow persistent
      walks over collagen IV and quick Brownian walks over fibronectin. At high cell
      density, collagen IV favored the self-assembly of B lymphocytes into clusters
      endowed with collective coordination, while fibronectin stimulated individual
      motility. We show that this behavioral plasticity is controlled by acto-myosin
      dependent adhesive and Arp2/3-dependent protrusive actin pools, respectively. Our
      study reveals the adaptive nature of B lymphocyte motility and group dynamics,
      which are shaped by an interplay between and cell:matrix and cell:cell
      interactions.

PMID- 29643415
TI  - Proteomic profiling of human cancer pseudopodia for the identification of anti
      metastatic drug candidates.
AB  - Cancer metastasis causes approximately 90% of all cancer-related death and
      independent of the advancement of cancer therapy, a majority of late stage
      patients suffers from metastatic cancer. Metastasis implies cancer cell migration
      and invasion throughout the body. Migration requires the formation of pseudopodia
      in the direction of movement, but a detailed understanding of this process and
      accordingly strategies of prevention remain elusive. Here, we use quantitative
      proteomic profiling of human cancer pseudopodia to examine this mechanisms
      essential to metastasis formation, and identify potential candidates for
      pharmacological interference with the process. We demonstrate that Prohibitins
      (PHBs) are significantly enriched in the pseudopodia fraction derived from cancer
      cells, and knockdown of PHBs, as well as their chemical inhibition through
      Rocaglamide (Roc-A), efficiently reduces cancer cell migration.

PMID- 29643417
TI  - Proteins clog neural stem cell activation.

PMID- 29643416
TI  - A retrospective study on association between obesity and cardiovascular risk
      diseases with aging in Chinese adults.
AB  - This study aimed to investigate the prevalence of overweight and obesity and its
      relationship with cardiovascular risk diseases among different sex and age groups
      in an urban Chinese adult population. A retrospective analysis was performed on
      384,061 Chinese adults aged 20 years and older in Nanjing. The age-standardized
      prevalence of overweight and obesity was 42.8% and 13.2% in men and 23.9% and
      6.6% in women. A gradually increasing trend was observed in the prevalence of
      overweight and obesity from 2008 to 2016, especially in individuals aged 20~39
      years. Overweight and obesity were significantly associated with increased risks
      of dyslipidemia, diabetes mellitus, hypertension, and hyperuricemia. Age weakened
      such relationship for both genders, which spiked in individuals aged 20~39 years.
      For men and women aged 20~39 years, the OR (95% CI) of obesity reached 4.23 (4.01
      4.47) and 5.29 (4.63-6.04) for dyslipidemia, 3.70 (2.97-4.60) and 6.38 (3.86
      10.55) for diabetes mellitus, 6.19 (5.76-6.64) and 9.36 (7.86-11.13) for
      hypertension, and 3.66 (3.45-3.88) and 6.65 (5.70-7.74) for hyperuricemia,
      respectively. The increasing trend in the epidemic of overweight and obesity is a
      risk factor for cardiovascular risk diseases in Chinese adults, especially in
      individuals aged 20~39 years.

PMID- 29643418
TI  - Contextual determinants of TGFbeta action in development, immunity and cancer.
AB  - Few cell signals match the impact of the transforming growth factor-beta
      (TGFbeta) family in metazoan biology. TGFbeta cytokines regulate cell fate
      decisions during development, tissue homeostasis and regeneration, and are major
      players in tumorigenesis, fibrotic disorders, immune malfunctions and various
      congenital diseases. The effects of the TGFbeta family are mediated by a
      combinatorial set of ligands and receptors and by a common set of receptor
      activated mothers against decapentaplegic homologue (SMAD) transcription factors,
      yet the effects can differ dramatically depending on the cell type and the
      conditions. Recent progress has illuminated a model of TGFbeta action in which
      SMADs bind genome-wide in partnership with lineage-determining transcription
      factors and additionally integrate inputs from other pathways and the chromatin
      to trigger specific cellular responses. These new insights clarify the operating
      logic of the TGFbeta pathway in physiology and disease.

PMID- 29643419
TI  - Author Correction: Synergistic effect of human Bone Morphogenic Protein-2 and
      Mesenchymal Stromal Cells on chronic wounds through hypoxia-inducible factor-1
      alpha induction.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 29643420
TI  - Publisher Correction: Alteration in Fluidity of Cell Plasma Membrane in
      Huntington Disease Revealed by Spectral Phasor Analysis.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 29643421
TI  - Serpine1 Knockdown Enhances MMP Activity after Flexor Tendon Injury in Mice:
      Implications for Adhesions Therapy.
AB  - Injuries to flexor tendons can be complicated by fibrotic adhesions, which
      severely impair the function of the hand. Adhesions have been associated with TGF
      beta1, which causes upregulation of PAI-1, a master suppressor of protease
      activity, including matrix metalloproteinases (MMP). In the present study, the
      effects of inhibiting PAI-1 in murine zone II flexor tendon injury were evaluated
      utilizing knockout (KO) mice and local nanoparticle-mediated siRNA delivery. In
      the PAI-1 KO murine model, reduced adherence of injured tendon to surrounding
      subcutaneous tissue and accelerated recovery of normal biomechanical properties
      compared to wild type controls were observed. Furthermore, MMP activity was
      significantly increased in the injured tendons of the PAI-1 KO mice, which could
      explain their reduced adhesions and accelerated remodeling. These data
      demonstrate that PAI-1 mediates fibrotic adhesions in injured flexor tendons by
      suppressing MMP activity. In vitro siRNA delivery to silence Serpine1 expression
      after treatment with TGF-beta1 increased MMP activity. Nanoparticle-mediated
      delivery of siRNA targeting Serpine1 in injured flexor tendons significantly
      reduced target gene expression and subsequently increased MMP activity.
      Collectively, the data demonstrate that PAI-1 can be a druggable target for
      treating adhesions and accelerating the remodeling of flexor tendon injuries.

PMID- 29643422
TI  - Chasing genetic structure in coralligenous reef invertebrates: patterns,
      criticalities and conservation issues.
AB  - Conservation of coastal habitats is a global issue, yet biogenic reefs in
      temperate regions have received very little attention. They have a broad
      geographic distribution and are a key habitat in marine ecosystems impacted by
      human activities. In the Mediterranean Sea coralligenous reefs are biodiversity
      hot spots and are classified as sensitive habitats deserving conservation.
      Genetic diversity and structure influence demographic, ecological and
      evolutionary processes in populations and play a crucial role in conservation
      strategies. Nevertheless, a comprehensive view of population genetic structure of
      coralligenous species is lacking. Here, we reviewed the literature on the genetic
      structure of sessile and sedentary invertebrates of the Mediterranean
      coralligenous reefs. Linear regression models and meta-analytic approaches are
      used to assess the contributions of genetic markers, phylum, pelagic larval
      duration (PLD) and geographical distance to the population genetic structure. Our
      quantitative approach highlight that 1) most species show a significant genetic
      structure, 2) structuring differs between phyla, and 3) PLD does not appear to be
      a major driver of the structuring. We discuss the implication of these finding
      for the management and conservation, suggesting research areas that deserve
      attention, and providing recommendations for broad assessment and monitoring of
      genetic diversity in biogenic reefs species.

PMID- 29643423
TI  - Bayesian-Driven First-Principles Calculations for Accelerating Exploration of
      Fast Ion Conductors for Rechargeable Battery Application.
AB  - Safe and robust batteries are urgently requested today for power sources of
      electric vehicles. Thus, a growing interest has been noted for fabricating those
      with solid electrolytes. Materials search by density functional theory (DFT)
      methods offers great promise for finding new solid electrolytes but the
      evaluation is known to be computationally expensive, particularly on ion
      migration property. In this work, we proposed a Bayesian-optimization-driven DFT
      based approach to efficiently screen for compounds with low ion migration
      energies ([Formula: see text]. We demonstrated this on 318 tavorite-type Li- and
      Na-containing compounds. We found that the scheme only requires ~30% of the total
      DFT-[Formula: see text] evaluations on the average to recover the optimal
      compound ~90% of the time. Its recovery performance for desired compounds in the
      tavorite search space is ~2* more than random search (i.e., for [Formula: see
      text] < 0.3 eV). Our approach offers a promising way for addressing computational
      bottlenecks in large-scale material screening for fast ionic conductors.

PMID- 29643424
TI  - Poultry hatcheries as potential reservoirs for antimicrobial-resistant
      Escherichia coli: A risk to public health and food safety.
AB  - Hatcheries have the power to spread antimicrobial resistant (AMR) pathogens
      through the poultry value chain because of their central position in the poultry
      production chain. Currently, no information is available about the presence of
      AMR Escherichia coli strains and the antibiotic resistance genes (ARGs) they
      harbor within hatchezries. Therefore, this study aimed to investigate the
      possible involvement of hatcheries in harboring hemolytic AMR E. coli. Serotyping
      of the 65 isolated hemolytic E. coli revealed 15 serotypes with the ability to
      produce moderate biofilms, and shared susceptibility to cephradine and fosfomycin
      and resistance to spectinomycin. The most common beta-lactam resistance gene was
      blaTEM, followed by blaOXA-1, blaMOX-like, blaCIT-like, blaSHV and blaFOX.
      Hierarchical clustering of E. coli isolates based on their phenotypic and
      genotypic profiles revealed separation of the majority of isolates from
      hatchlings and the hatchery environments, suggesting that hatchling and
      environmental isolates may have different origins. The high frequency of beta
      lactam resistance genes in AMR E. coli from chick hatchlings indicates that
      hatcheries may be a reservoir of AMR E. coli and can be a major contributor to
      the increased environmental burden of ARGs posing an eminent threat to poultry
      and human health.

PMID- 29643426
TI  - Publisher Correction: Optimization of large animal MI models; a systematic
      analysis of control groups from preclinical studies.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 29643425
TI  - A novel two-score system for interferon status segregates autoimmune diseases and
      correlates with clinical features.
AB  - Measurement of type I interferon (IFN-I) has potential to diagnose and stratify
      autoimmune diseases, but existing results have been inconsistent. Interferon
      stimulated-gene (ISG) based methods may be affected by the modularity of the ISG
      transcriptome, cell-specific expression, response to IFN-subtypes and bimodality
      of expression. We developed and clinically validated a 2-score system (IFN-Score
      A and -B) using Factor Analysis of 31 ISGs measured by TaqMan selected from 3-IFN
      annotated modules. We evaluated these scores using in-vitro IFN stimulation as
      well as in sorted cells then clinically validated in a cohort of 328 autoimmune
      disease patients and healthy controls. ISGs varied in response to IFN-subtypes
      and both scores varied between cell subsets. IFN-Score-A differentiated Systemic
      Lupus Erythematosus (SLE) from both Rheumatoid Arthritis (RA) and Healthy
      Controls (HC) (both p < 0.001), while IFN-Score-B differentiated SLE and RA from
      HC (both p < 0.001). In SLE, both scores were associated with cutaneous and
      hematological (all p < 0.05) but not musculoskeletal disease activity. Comparing
      with bimodal (IFN-high/low) classification, significant differences in IFN-scores
      were found between diagnostic groups within the IFN-high group. Our continuous 2
      score system is more clinically relevant than a simple bimodal classification of
      IFN status. This system should allow improvement in diagnosis, stratification,
      and therapy in IFN-mediated autoimmunity.

PMID- 29643427
TI  - Author Correction: Coherent scatter-controlled phase-change grating structures in
      silicon using femtosecond laser pulses.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 29643428
TI  - Changing patterns of human migrations shaped the global population structure of
      Mycobacterium tuberculosis in France.
AB  - Mycobacterium tuberculosis (Mtb) exhibits a structured phylogeographic
      distribution worldwide linked with human migrations. We sought to infer how the
      interactions between distinct human populations shape the global population
      structure of Mtb on a regional scale. We applied the recently described
      timescaled haplotypic density (THD) technique on 638 minisatellite-based Mtb
      genotypes from French tuberculosis patients. THD with a long-term (200 y)
      timescale indicated that Mtb population in France had been mostly influenced by
      interactions with Eastern and Southern Europe and, to a lesser extent, Northern
      and Middle Africa, consistent with historical migrations favored by geographic
      proximity or commercial exchanges with former French colonies. Restricting the
      timescale to 20 y, THD identified a sustained influence of Northern Africa, but
      not Europe where tuberculosis incidence decreased sharply. Evolving interactions
      between human populations, thus, measurably influence the local population
      structure of Mtb. Relevant information on such interactions can be inferred using
      THD from Mtb genotypes.

PMID- 29643429
TI  - Asymmetric ommatidia count and behavioural lateralization in the ant Temnothorax
      albipennis.
AB  - Workers of the house-hunting ant Temnothorax albipennis rely on visual edge
      following and landmark recognition to navigate their rocky environment, and they
      also exhibit a leftward turning bias when exploring unknown nest sites. We used
      electron microscopy to count the number of ommatidia composing the compound eyes
      of workers, males and queens, to make an approximate assessment of their relative
      sampling resolution; and to establish whether there is an asymmetry in the number
      of ommatidia composing the workers' eyes, which might provide an observable,
      mechanistic explanation for the turning bias. We hypothesise that even small
      asymmetries in relative visual acuity between left and right eyes could be
      magnified by developmental experience into a symmetry-breaking turning preference
      that results in the inferior eye pointing toward the wall. Fifty-six workers were
      examined: 45% had more ommatidia in the right eye, 36% more in the left, and 20%
      an equal number. A tentative connection between relative ommatidia count for each
      eye and turning behaviour was identified, with a stronger assessment of
      behavioural lateralization before imaging and a larger sample suggested for
      further work. There was a clear sexual dimorphism in ommatidia counts between
      queens and males.

PMID- 29643430
TI  - Highly Interactive Brain-Computer Interface Based on Flicker-Free Steady-State
      Motion Visual Evoked Potential.
AB  - Visual evoked potential-based brain-computer interfaces (BCIs) have been widely
      investigated because of their easy system configuration and high information
      transfer rate (ITR). However, the uncomfortable flicker or brightness modulation
      of existing methods restricts the practical interactivity of BCI applications. In
      our study, a flicker-free steady-state motion visual evoked potential (FF-SSMVEP)
      based BCI was proposed. Ring-shaped motion checkerboard patterns with oscillating
      expansion and contraction motions were presented by a high-refresh-rate display
      for visual stimuli, and the brightness of the stimuli was kept constant. Compared
      with SSVEPs, few harmonic responses were elicited by FF-SSMVEPs, and the
      frequency energy of SSMVEPs was concentrative. These FF-SSMVEPs evoked "single
      fundamental peak" responses after signal processing without harmonic and
      subharmonic peaks. More stimulation frequencies could thus be selected to elicit
      more responding fundamental peaks without overlap with harmonic peaks. A 40
      target online SSMVEP-based BCI system was achieved that provided an ITR up to
      1.52 bits per second (91.2 bits/min), and user training was not required to use
      this system. This study also demonstrated that the FF-SSMVEP-based BCI system has
      low contrast and low visual fatigue, offering a better alternative to
      conventional SSVEP-based BCIs.

PMID- 29643432
TI  - Author Correction: The hypothesis that Helicobacter pylori predisposes to
      Alzheimer's disease is biologically plausible.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 29643431
TI  - An estradiol-independent BDNF-NPY cascade is involved in the antidepressant
      effect of mechanical acupuncture instruments in ovariectomized rats.
AB  - Menopause-related depression devastates women's quality of life after middle age.
      Previous research has shown that estrogen hormone therapy has serious adverse
      effects; thus, complementary and integrative therapies have been considered
      clinically. The present study investigates whether stimulation of an acupoint
      using a mechanical acupuncture instrument (MAI) can mitigate depression-like
      behavior caused by estrogen deficiency in ovariectomized (OVX) rats. The animals
      were divided into Sham OVX, OVX, OVX + Sameumgyo (SP6) and OVX + NonAcu (non
      acupuncture point) groups. MAI stimulation significantly increased the total
      distance traveled in the open-field test and the number of open-arm entries in
      the elevated plus maze and decreased the duration of immobility in the forced
      swim test. In addition to this decrease in depression-like behavior, brain
      derived neurotrophic factor (BDNF) and neuropeptide Y (NPY) release increased in
      the hippocampus in response to MAI treatment, but estradiol levels did not
      recover. Furthermore, microinjection of the BDNF receptor antagonist ANA-12 (0.1
      pmol/1 MUl) into the hippocampus before MAI stimulation significantly suppressed
      the recovery of NPY levels. Taken together, these findings indicate that MAI
      stimulation at SP6 facilitates an estradiol-independent BDNF-NPY cascade, which
      may contribute to its antidepressant effects in OVX rats, an animal model of
      menopausal disorders.

PMID- 29643433
TI  - Neurofibromin knockdown in glioma cell lines is associated with changes in
      cytokine and chemokine secretion in vitro.
AB  - The neurofibromin-1 tumor suppressor gene (NF1) is altered in approximately 20%
      of sporadic glioblastoma (GBM) cases. NF1 deficient GBM frequently shows a
      mesenchymal gene expression signature, suggesting a relationship between NF1
      status and the tumor microenvironment. To identify changes in the production of
      secreted cytokines/chemokines in NF1 deficient glioma, we applied cytokine arrays
      to conditioned media from a panel of three GBM cell lines after siRNA-mediated
      NF1 knockdown. We identified increased secretion of platelet-derived growth
      factor AA (PDGF-AA), chitinase-3-like protein 1 (CHI3L1), interleukin-8 (IL-8),
      and endoglin (ENG) in different subsets of these cell lines. Secretion was
      associated with induction of the corresponding messenger RNA, suggesting a
      mechanism involving transcriptional upregulation. By contrast, in non-transformed
      immortalized normal human astrocytes, PDGF-AA secretion was increased upon NF1
      knockdown, while secreted CHI3L1, ENG, and IL-8 were reduced or unchanged.
      Analysis of The Cancer Genome Atlas confirmed a relationship between glioma NF1
      status and ENG and CHI3L1 in tumor samples. Overall, this study identifies
      candidate changes in secreted proteins from NF1 deficient glioma cells that could
      influence the tumor microenvironment, and suggests a direct link between NF1 loss
      and increased tumor cell production of CHI3L1 and endoglin, two factors
      implicated in mesenchymal identity in glioblastoma.

PMID- 29643434
TI  - Genetic homogeneity of goat malaria parasites in Asia and Africa suggests their
      expansion with domestic goat host.
AB  - Plasmodium was first identified in a goat in Angola in 1923, and only recently
      characterized by DNA isolation from a goat blood sample in Zambia. Goats were
      first domesticated in the Fertile Crescent approximately 10,000 years ago, and
      are now globally distributed. It is not known if the Plasmodium identified in
      African goats originated from parasites circulating in the local ungulates, or if
      it co-evolved in the goat before its domestication. To address this question, we
      performed PCR-based surveillance using a total of 1,299 goat blood samples
      collected from Sudan and Kenya in Africa, Iran in west Asia, and Myanmar and
      Thailand in southeast Asia. Plasmodium DNA was detected from all locations,
      suggesting that the parasite is not limited to Africa, but widely distributed.
      Whole mitochondrial DNA sequences revealed that there was only one nucleotide
      substitution between Zambian/Kenyan samples and others, supporting the existence
      of a goat-specific Plasmodium species, presumably Plasmodium caprae, rather than
      infection of goats by local ungulate malaria parasites. We also present the first
      photographic images of P. caprae, from one Kenyan goat sample.

PMID- 29643435
TI  - Higher leukocyte count predicts 3-month poor outcome of ruptured cerebral
      aneurysms.
AB  - It is not fully established whether leukocyte can predict the poor outcome for
      ruptured cerebral aneurysms (CA) or not. Here, we retrospectively analyzed the
      clinical data of 428 patients with ruptured CA between 2010 and 2015. Patients'
      demographic data, including gender, age, history of smoking, alcohol,
      hypertension, diabetes and hypercholesterolemia, Hunt-Hess and Fisher grade,
      occurrence of hydrocephalus, aneurysm location, time to surgery, delayed ischemic
      neurological deficit (DIND) and peak leukocyte of blood test from day 1 to 3
      after aneurysmal rupture were recorded and analyzed. In the multivariable
      analysis model, gender, Fisher grade, time to surgery and hydrocephalus were not
      relevant to poor outcome. However, Hunt-Hess grade, DIND and preoperative
      leukocyte count (>13.84 * 109/L) were significantly associated with adverse
      outcome. The respective increased risks were 5.2- (OR5.24, 95% CI 1.67-16.50, p =
      0.005), 6.2-(OR 6.24, 95% CI 3.55-10.99, p < 0.001) and 10.9-fold (OR 9.35, 95%
      CI 5.98-19.97, p < 0.001). The study revealed that Hunt-Hess grade, DIND and
      preoperative leukocyte count (>13.84 * 109/L) were independent risk factors for
      poor outcome of ruptured CA at 3 months. Higher leukocyte count is a convenient
      and useful marker to predict 3-month poor outcome for ruptured CA.

PMID- 29643436
TI  - Satellite DNA in Vicia faba is characterized by remarkable diversity in its
      sequence composition, association with centromeres, and replication timing.
AB  - Satellite DNA, a class of repetitive sequences forming long arrays of tandemly
      repeated units, represents substantial portions of many plant genomes yet remains
      poorly characterized due to various methodological obstacles. Here we show that
      the genome of the field bean (Vicia faba, 2n = 12), a long-established model for
      cytogenetic studies in plants, contains a diverse set of satellite repeats, most
      of which remained concealed until their present investigation. Using next
      generation sequencing combined with novel bioinformatics tools, we reconstructed
      consensus sequences of 23 novel satellite repeats representing 0.008-2.700% of
      the genome and mapped their distribution on chromosomes. We found that in
      addition to typical satellites with monomers hundreds of nucleotides long, V.
      faba contains a large number of satellite repeats with unusually long monomers
      (687-2033 bp), which are predominantly localized in pericentromeric regions.
      Using chromatin immunoprecipitation with CenH3 antibody, we revealed an
      extraordinary diversity of centromeric satellites, consisting of seven repeats
      with chromosome-specific distribution. We also found that in spite of their
      different nucleotide sequences, all centromeric repeats are replicated during mid
      S phase, while most other satellites are replicated in the first part of late S
      phase, followed by a single family of FokI repeats representing the latest
      replicating chromatin.

PMID- 29643437
TI  - Crystal structure of Bacillus cereus flagellin and structure-guided fusion
      protein designs.
AB  - Flagellin is a major component of the flagellar filament. Flagellin also
      functions as a specific ligand that stimulates innate immunity through direct
      interaction with Toll-like receptor 5 (TLR5) in the host. Because flagellin
      activates the immune response, it has been of interest to develop as a vaccine
      adjuvant in subunit vaccines or antigen fusion vaccines. Despite the widespread
      application of flagellin fusion in preventing infectious diseases, flagellin
      antigen fusion designs have never been biophysically and structurally
      characterized. Moreover, flagellin from Salmonella species has been used
      extensively despite containing hypervariable regions not required for TLR5 that
      can cause an unexpected immune response. In this study, flagellin from Bacillus
      cereus (BcFlg) was identified as the smallest flagellin molecule containing only
      the conserved TLR5-activating D0 and D1 domains. The crystal structure of BcFlg
      was determined to provide a scheme for fusion designs. Through homology-based
      modeling and comparative structural analyses, diverse fusion strategies were
      proposed. Moreover, cellular and biophysical analysis of an array of fusion
      constructs indicated that insertion fusion at BcFlg residues 178-180 does not
      interfere with the protein stability or TLR5-stimulating capacity of flagellin,
      suggesting its usefulness in the development and optimization of flagellin fusion
      vaccines.

PMID- 29643438
TI  - Trends in the Timing and Magnitude of Ice-Jam Floods in Canada.
AB  - Ice-jam floods (IJFs) are important hydrological and hydraulic events in the
      northern hemisphere that are of major concern for citizens, authorities,
      insurance companies and government agencies. In recent years, there have been
      advances in assessing and quantifying climate change impacts on river ice
      processes, however, an understanding of climate change and regulation impacts on
      the timing and magnitude of IJFs remains limited. This study presents a global
      overview of IJF case studies and discusses IJF risks in North America, one of the
      most IJF prone regions according to literature. Then an assessment of shifts in
      the timing and magnitude of IJFs in Canada is presented analyzing flow data from
      1107 hydrometric stations across Canada for the period from 1903 to 2015. The
      analyses show clear signals of climate change and regulation impacts in the
      timing and magnitude of IJFs, particularly in small basins.

PMID- 29643439
TI  - Author Correction: Salinity stratification controlled productivity variation over
      300 ky in the Bay of Bengal.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 29643440
TI  - Bacterial Pore-Forming Toxins Promote the Activation of Caspases in Parallel to
      Necroptosis to Enhance Alarmin Release and Inflammation During Pneumonia.
AB  - Pore-forming toxins are the most common virulence factor in pathogenic bacteria.
      They lead to membrane permeabilization and cell death. Herein, we show that
      respiratory epithelial cells (REC) undergoing bacterial pore-forming toxin (PFT)
      induced necroptosis simultaneously experienced caspase activation independently
      of RIPK3. MLKL deficient REC treated with a pan-caspase inhibitor were protected
      in an additive manner against PFT-induced death. Subsequently, cleaved versions
      of caspases-2, -4 and -10 were detected within REC undergoing necroptosis by
      immunoblots and monoclonal antibody staining. Caspase activation was observed in
      lung samples from mice and non-human primates experiencing Gram-negative and Gram
      positive bacterial pneumonia, respectively. During apoptosis, caspase activation
      normally leads to cell shrinkage, nuclear condensation, and immunoquiescent
      death. In contrast, caspase activity during PFT-induced necroptosis increased the
      release of alarmins to the extracellular milieu. Caspase-mediated alarmin release
      was found sufficient to activate resting macrophages, leading to Interleukin-6
      production. In a mouse model of Gram-negative pneumonia, deletion of caspases -2
      and -11, the mouse orthologue of caspase-4, reduced pulmonary inflammation,
      immune cell infiltration and lung damage. Thus, our study describes a previously
      unrecognized role for caspase activation in parallel to necroptosis, and
      indicates that their activity plays a critical pro-inflammatory role during
      bacterial pneumonia.

PMID- 29643442
TI  - Author Correction: EEG Transients in the Sigma Range During non-REM Sleep Predict
      Learning in Dogs.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 29643441
TI  - The sequence of cortical activity inferred by response latency variability in the
      human ventral pathway of face processing.
AB  - Variability in neuronal response latency has been typically considered caused by
      random noise. Previous studies of single cells and large neuronal populations
      have shown that the temporal variability tends to increase along the visual
      pathway. Inspired by these previous studies, we hypothesized that functional
      areas at later stages in the visual pathway of face processing would have larger
      variability in the response latency. To test this hypothesis, we used
      magnetoencephalographic data collected when subjects were presented with images
      of human faces. Faces are known to elicit a sequence of activity from the primary
      visual cortex to the fusiform gyrus. Our results revealed that the fusiform gyrus
      showed larger variability in the response latency compared to the calcarine
      fissure. Dynamic and spectral analyses of the latency variability indicated that
      the response latency in the fusiform gyrus was more variable than in the
      calcarine fissure between 70 ms and 200 ms after the stimulus onset and between 4
      Hz and 40 Hz, respectively. The sequential processing of face information from
      the calcarine sulcus to the fusiform sulcus was more reliably detected based on
      sizes of the response variability than instants of the maximal response peaks.
      With two areas in the ventral visual pathway, we show that the variability in
      response latency across brain areas can be used to infer the sequence of cortical
      activity.

PMID- 29643443
TI  - DNA methylation-based biomarkers and the epigenetic clock theory of ageing.
AB  - Identifying and validating molecular targets of interventions that extend the
      human health span and lifespan has been difficult, as most clinical biomarkers
      are not sufficiently representative of the fundamental mechanisms of ageing to
      serve as their indicators. In a recent breakthrough, biomarkers of ageing based
      on DNA methylation data have enabled accurate age estimates for any tissue across
      the entire life course. These 'epigenetic clocks' link developmental and
      maintenance processes to biological ageing, giving rise to a unified theory of
      life course. Epigenetic biomarkers may help to address long-standing questions in
      many fields, including the central question: why do we age?

PMID- 29643444
TI  - A Bowman-Birk type chymotrypsin inhibitor peptide from the amphibian, Hylarana
      erythraea.
AB  - The first amphibian skin secretion-derived Bowman-Birk type chymotrypsin
      inhibitor is described here from the Asian green frog, Hylarana erythraea, and
      was identified by use of molecular cloning and tandem mass spectrometric amino
      acid sequencing. It was named Hylarana erythraea chymotrypsin inhibitor (HECI)
      and in addition to inhibition of chymotrypsin (Ki = 3.92 +/- 0.35 MUM), the
      peptide also inhibited the 20 S proteasome (Ki = 8.55 +/- 1.84  MUM).
      Additionally, an analogue of HECI, named K9-HECI, in which Phe9 was substituted
      by Lys9 at the P1 position, was functional as a trypsin inhibitor. Both peptides
      exhibited anti-proliferation activity against the human cancer cell lines, H157,
      PC-3 and MCF-7, up to a concentration of 1 mM and possessed a low degree of
      cytotoxicity on normal cells, HMEC-1. However, HECI exhibited higher anti
      proliferative potency against H157. The results indicate that HECI, inhibiting
      chymotryptic-like activity of proteasome, could provide new insights in treatment
      of lung cancer.

PMID- 29643445
TI  - Author Correction: The Incipient Motion Features of Sediment from Yangtze
      Estuary: Annular Flume Experiments.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 29643446
TI  - Author Correction: A novel quantitative PCR mediated by high-fidelity DNA
      polymerase.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 29643447
TI  - Mimicking Electromagnetic Wave Coupling in Tokamak Plasma with Fishnet
      Metamaterials.
AB  - This paper reports a fishnet hyperbolic metamaterial that mimics the
      electromagnetic properties of magnetically confined plasma. These electromagnetic
      properties are strongly anisotropic and different from any conventional material,
      therefore cannot be mimicked by bulk materials. The structure is made of a stack
      of thin copper grids spaced by Rohacell foam. We numerically and experimentally
      show that this kind of structuration matches well the properties of a homogeneous
      plasma. This solution breaks a long-lasting bottleneck and will accelerate the
      development of high-frequency heating systems to be used in nuclear fusion.

PMID- 29643449
TI  - An Automatic Diagnosis Method of Facial Acne Vulgaris Based on Convolutional
      Neural Network.
AB  - In this paper, we present a new automatic diagnosis method for facial acne
      vulgaris which is based on convolutional neural networks (CNNs). To overcome the
      shortcomings of previous methods which were the inability to classify enough
      types of acne vulgaris. The core of our method is to extract features of images
      based on CNNs and achieve classification by classifier. A binary-classifier of
      skin-and-non-skin is used to detect skin area and a seven-classifier is used to
      achieve the classification task of facial acne vulgaris and healthy skin. In the
      experiments, we compare the effectiveness of our CNN and the VGG16 neural network
      which is pre-trained on the ImageNet data set. We use a ROC curve to evaluate the
      performance of binary-classifier and use a normalized confusion matrix to
      evaluate the performance of seven-classifier. The results of our experiments show
      that the pre-trained VGG16 neural network is effective in extracting features
      from facial acne vulgaris images. And the features are very useful for the follow
      up classifiers. Finally, we try applying the classifiers both based on the pre
      trained VGG16 neural network to assist doctors in facial acne vulgaris diagnosis.

PMID- 29643448
TI  - Shorter sleep duration and better sleep quality are associated with greater
      tissue density in the brain.
AB  - Poor sleep quality is associated with unfavorable psychological measurements,
      whereas sleep duration has complex relationships with such measurements. The aim
      of this study was to identify the associations between microstructural properties
      of the brain and sleep duration/sleep quality in a young adult. The associations
      between mean diffusivity (MD), a measure of diffusion tensor imaging (DTI), and
      sleep duration/sleep quality were investigated in a study cohort of 1201 normal
      young adults. Positive correlations between sleep duration and MD of widespread
      areas of the brain, including the prefrontal cortex (PFC) and the dopaminergic
      systems, were identified. Negative correlations between sleep quality and MD of
      the widespread areas of the brain, including the PFC and the right hippocampus,
      were also detected. Lower MD has been previously associated with more neural
      tissues in the brain. Further, shorter sleep duration was associated with greater
      persistence and executive functioning (lower Stroop interference), whereas good
      sleep quality was associated with states and traits relevant to positive affects.
      These results suggest that bad sleep quality and longer sleep duration were
      associated with aberrant neurocognitive measurements in the brain in healthy
      young adults.

PMID- 29643450
TI  - Author Correction: Methods for Scarless, Selection-Free Generation of Human Cells
      and Allele-Specific Functional Analysis of Disease-Associated SNPs and Variants
      of Uncertain Significance.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 29643451
TI  - Author Correction: Optimised metrics for CRISPR-KO screens with second-generation
      gRNA libraries.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 29643452
TI  - Author Correction: Contributions of cuticle permeability and enzyme
      detoxification to pyrethroid resistance in the major malaria vector Anopheles
      gambiae.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 29643453
TI  - Alternative SNP detection platforms, HRM and biosensors, for varietal
      identification in Vitis vinifera L. using F3H and LDOX genes.
AB  - The wine sector requires quick and reliable methods for Vitis vinifera L.
      varietal identification. The number of V. vinifera varieties is estimated in
      about 5,000 worldwide. Single Nucleotide Polymorphisms (SNPs) represent the most
      basic and abundant form of genetic sequence variation, being adequate for
      varietal discrimination. The aim of this work was to develop DNA-based assays
      suitable to detect SNP variation in V. vinifera, allowing varietal
      discrimination. Genotyping by sequencing allowed the detection of eleven SNPs on
      two genes of the anthocyanin pathway, the flavanone 3-hydroxylase (F3H, EC:
      1.14.11.9), and the leucoanthocyanidin dioxygenase (LDOX, EC 1.14.11.19; synonym
      anthocyanidin synthase, ANS) in twenty V. vinifera varieties. Three High
      Resolution Melting (HRM) assays were designed based on the sequencing
      information, discriminating five of the 20 varieties: Alicante Bouschet,
      Donzelinho Tinto, Merlot, Moscatel Galego and Tinta Roriz. Sanger sequencing of
      the HRM assay products confirmed the HRM profiles. Three probes, with different
      lengths and sequences, were used as bio-recognition elements in an optical
      biosensor platform based on a long period grating (LPG) fiber optic sensor. The
      label free platform detected a difference of a single SNP using genomic DNA
      samples. The two different platforms were successfully applied for grapevine
      varietal identification.

PMID- 29643454
TI  - Activation of the DnaK-ClpB Complex is Regulated by the Properties of the Bound
      Substrate.
AB  - The chaperone ClpB in bacteria is responsible for the reactivation of aggregated
      proteins in collaboration with the DnaK system. Association of these chaperones
      at the aggregate surface stimulates ATP hydrolysis, which mediates substrate
      remodeling. However, a question that remains unanswered is whether the
      bichaperone complex can be selectively activated by substrates that require
      remodeling. We find that large aggregates or bulky, native-like substrates
      activates the complex, whereas a smaller, permanently unfolded protein or
      extended, short peptides fail to stimulate it. Our data also indicate that ClpB
      interacts differently with DnaK in the presence of aggregates or small peptides,
      displaying a higher affinity for aggregate-bound DnaK, and that DnaK-ClpB
      collaboration requires the coupled ATPase-dependent remodeling activities of both
      chaperones. Complex stimulation is mediated by residues at the beta subdomain of
      DnaK substrate binding domain, which become accessible to the disaggregase when
      the lid is allosterically detached from the beta subdomain. Complex activation
      also requires an active NBD2 and the integrity of the M domain-ring of ClpB.
      Disruption of the M-domain ring allows the unproductive stimulation of the DnaK
      ClpB complex in solution. The ability of the DnaK-ClpB complex to discriminate
      different substrate proteins might allow its activation when client proteins
      require remodeling.

PMID- 29643455
TI  - Implementation of a Toffoli gate using an array of coupled cavities in a single
      step.
AB  - The Toffoli gate (controlled-controlled-NOT gate) is one typical three-qubit
      gate, it plus a Hadamard gate form a universal set of gates in quantum
      computation. We present an efficient method to implement the Toffoli gate using
      an array of coupled cavities with one three-level atom in each cavity. The large
      detuning between atoms and classical (quantum) fields plays an important role and
      the gate is implemented in one-step. The quantum information is encoded into the
      low-lying states of identical atoms and it is convenient to address qubit
      individually. Based on the Markovian master equation, it is shown that the scheme
      to implement the Toffoli gate is robust against the decoherence.

PMID- 29643456
TI  - Publisher Correction: Metacognitive impairments extend perceptual decision making
      weaknesses in compulsivity.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 29643457
TI  - Catalytically active inclusion bodies of L-lysine decarboxylase from E. coli for
      1,5-diaminopentane production.
AB  - Sustainable and eco-efficient alternatives for the production of platform
      chemicals, fuels and chemical building blocks require the development of stable,
      reusable and recyclable biocatalysts. Here we present a novel concept for the
      biocatalytic production of 1,5-diaminopentane (DAP, trivial name: cadaverine)
      using catalytically active inclusion bodies (CatIBs) of the constitutive L-lysine
      decarboxylase from E. coli (EcLDCc-CatIBs) to process L-lysine-containing culture
      supernatants from Corynebacterium glutamicum. EcLDCc-CatIBs can easily be
      produced in E. coli followed by a simple purification protocol yielding up to 43%
      dry CatIBs per dry cell weight. The stability and recyclability of EcLDCc-CatIBs
      was demonstrated in (repetitive) batch experiments starting from L-lysine
      concentrations of 0.1 M and 1 M. EcLDC-CatIBs exhibited great stability under
      reaction conditions with an estimated half-life of about 54 h. High conversions
      to DAP of 87-100% were obtained in 30-60 ml batch reactions using approx. 180-300
      mg EcLDCc-CatIBs, respectively. This resulted in DAP titres of up to 88.4 g l-1
      and space-time yields of up to 660 gDAP l-1 d-1 per gram dry EcLDCc-CatIBs. The
      new process for DAP production can therefore compete with the currently best
      fermentative process as described in the literature.

PMID- 29643459
TI  - 1.5  degrees C carbon budget dependent on carbon cycle uncertainty and future non
      CO2 forcing.
AB  - Estimates of the 1.5  degrees C carbon budget vary widely among recent studies,
      emphasizing the need to better understand and quantify key sources of
      uncertainty. Here we quantify the impact of carbon cycle uncertainty and non-CO2
      forcing on the 1.5  degrees C carbon budget in the context of a prescribed 1.5 
      degrees C temperature stabilization scenario. We use Bayes theorem to weight
      members of a perturbed parameter ensemble with varying land and ocean carbon
      uptake, to derive an estimate for the fossil fuel (FF) carbon budget of 469 PgC
      since 1850, with a 95% likelihood range of (411,528) PgC. CO2 emissions from land
      use change (LUC) add about 230 PgC. Our best estimate of the total (FF + LUC)
      carbon budget for 1.5  degrees C is therefore 699 PgC, which corresponds to about
      11 years of current emissions. Non-CO2 greenhouse gas and aerosol emissions
      represent equivalent cumulative CO2 emissions of about 510 PgC and -180 PgC for
      1.5  degrees C, respectively. The increased LUC, high non-CO2 emissions and
      decreased aerosols in our scenario, cause the long-term FF carbon budget to
      decrease following temperature stabilization. In this scenario, negative
      emissions would be required to compensate not only for the increasing non-CO2
      climate forcing, but also for the declining natural carbon sinks.

PMID- 29643458
TI  - Pro-inflammatory cytokines activate hypoxia-inducible factor 3alpha via
      epigenetic changes in mesenchymal stromal/stem cells.
AB  - Human mesenchymal stromal/stem cells (hMSCs) emerged as a promising therapeutic
      tool for ischemic disorders, due to their ability to regenerate damaged tissues,
      promote angiogenesis and reduce inflammation, leading to encouraging, but still
      limited results. The outcomes in clinical trials exploring hMSC therapy are
      influenced by low cell retention and survival in affected tissues, partially
      influenced by lesion's microenvironment, where low oxygen conditions (i.e.
      hypoxia) and inflammation coexist. Hypoxia and inflammation are
      pathophysiological stresses, sharing common activators, such as hypoxia-inducible
      factors (HIFs) and NF-kappaB. HIF1alpha and HIF2alpha respond essentially to
      hypoxia, activating pathways involved in tissue repair. Little is known about the
      regulation of HIF3alpha. Here we investigated the role of HIF3alpha in vitro and
      in vivo. Human MSCs expressed HIF3alpha, differentially regulated by pro
      inflammatory cytokines in an oxygen-independent manner, a novel and still
      uncharacterized mechanism, where NF-kappaB is critical for its expression. We
      investigated if epigenetic modifications are involved in HIF3alpha expression by
      methylation-specific PCR and histone modifications. Robust hypermethylation of
      histone H3 was observed across HIF3A locus driven by pro-inflammatory cytokines.
      Experiments in a murine model of arteriotomy highlighted the activation of
      Hif3alpha expression in infiltrated inflammatory cells, suggesting a new role for
      Hif3alpha in inflammation in vivo.

PMID- 29643460
TI  - Retraction Note: Catalytic living ring-opening metathesis polymerization.
AB  - We the authors are retracting this Article because of our failure to reproduce
      the molecular weight dispersities (PDI) shown in Fig. 4 using the chain-transfer
      agent described in the paper (CTA1). While the degenerate chain-transfer
      mechanism described in Fig. 3 is correct, the best molecular weight dispersities
      that could be reproduced with the chain-transfer agent shown in the Article are
      much larger (PDI > 2.0) than reported.We have since studied the kinetics of CTA1
      in comparison with several other chain-transfer agents we are currently
      investigating and we now understand that the reactivity of CTA1 towards
      propagating ruthenium alkylidene complexes is very low. Very long monomer
      addition times would therefore have been necessary to gain control over the
      molecular weight distribution. Such long addition times would exceed the lifetime
      of the Grubbs catalyst in solution. Faster addition of the monomer has since
      repeatedly been shown to broaden the molecular weight dispersity.Additionally,
      the best chain-transfer agents we are currently investigating are orders of
      magnitude more reactive than CTA1 but give broader molecular weight dispersities
      than reported in Fig. 4. Molecular weight and dispersity control as shown in Fig.
      4 is therefore an inappropriate claim for CTA1.The authors deeply regret these
      errors and apologize to the community.

PMID- 29643461
TI  - Extending a Gray Lattice Boltzmann Model for Simulating Fluid Flow in Multi-Scale
      Porous Media.
AB  - A gray lattice Boltzmann model has previously been developed by the authors of
      this article to simulate fluid flow in porous media that contain both resolved
      pores and grains as well as aggregates of unresolved smaller pores and grains. In
      this model, a single parameter is introduced to prescribe the amount of fluid to
      be bounced back at each aggregate cell. This model has been shown to recover
      Darcy-Brinkman flow but with effective viscosity and permeability correlated
      through the model parameter. In this paper, we prove that the model parameter
      relates to the fraction of the solid phase of a sub-pore system for a specific
      set of bounce-back conditions. We introduce an additional parameter to the model,
      and this enables flow simulation in which cases with variable effective viscosity
      and permeability can be specified by selecting the two parameters independently.
      We verify and validate the model for layered channel cases and mathematically
      analyze fluid momentum and energy losses for the single- and two-parameter models
      to explain the roles of the parameters in their conservation. We introduce a
      strategy to upgrade our model to an isotropic version. We discuss the fundamental
      differences between our model and the Brinkman body-force LBM scheme.

PMID- 29643462
TI  - Environment-dependent striatal gene expression in the BACHD rat model for
      Huntington disease.
AB  - Huntington disease (HD) is an autosomal dominant neurodegenerative disorder
      caused by a mutation in the huntingtin (HTT) gene which results in progressive
      neurodegeneration in the striatum, cortex, and eventually most brain areas.
      Despite being a monogenic disorder, environmental factors influence HD
      characteristics. Both human and mouse studies suggest that mutant HTT (mHTT)
      leads to gene expression changes that harbor potential to be modulated by the
      environment. Yet, the underlying mechanisms integrating environmental cues into
      the gene regulatory program have remained largely unclear. To better understand
      gene-environment interactions in the context of mHTT, we employed RNA-seq to
      examine effects of maternal separation (MS) and environmental enrichment (EE) on
      striatal gene expression during development of BACHD rats. We integrated our
      results with striatal consensus modules defined on HTT-CAG length and age
      dependent co-expression gene networks to relate the environmental factors with
      disease progression. While mHTT was the main determinant of expression changes,
      both MS and EE were capable of modulating these disturbances, resulting in
      distinctive and in several cases opposing effects of MS and EE on consensus
      modules. This bivalent response to maternal separation and environmental
      enrichment may aid in explaining their distinct effects observed on disease
      phenotypes in animal models of HD and related neurodegenerative disorders.

PMID- 29643464
TI  - Osteopontin drives renal metabolic dysfunction in Alport syndrome.

PMID- 29643463
TI  - Diagnostic capacity of SD-OCT segmented ganglion cell complex versus retinal
      nerve fiber layer analysis for congenital glaucoma.
AB  - PURPOSE: To compare the diagnostic performance of circumpapillary retinal nerve
      fiber layer (cpRNFL) analysis versus segmented ganglion cell complex analysis
      both by spectral-domain optical coherence tomography (SD-OCT) in children with
      primary congenital glaucoma (PCG). METHODS: Participants were 40 children
      diagnosed with PCG and 60 healthy children. Ophthalmological data collected (for
      one eye per child) were cup-disc ratio (C/D) and axial length (AL). SD-OCT with
      automated segmentation was used to measure the thicknesses and volumes of the
      macular retinal nerve fiber layer (mRNFL), ganglion cell layer (GCL), and inner
      plexiform layer (IPL). For the cpRNFL measurements conventional S-D OCT software
      was used and the capacity of each method to discriminate between normal and
      glaucomatous eyes was compared. RESULTS: Mean age was 11.20 +/- 3.94 years for
      the glaucoma patients and 10.90 +/- 2.46 years for controls (p = 0.64). All
      measurements were reduced (thinner) in the glaucoma group, significantly so for:
      cpRNFL, GCL, IPL and outer-superior and outer-inferior quadrant mRNFL. According
      to their areas under the receiver operating characteristics curve (AUC), temporal
      superior cpRNFL (0.869) and outer superior GCL (0.840), IPL (0.799), and mRNFL
      (0.767) showed the better diagnostic capacity. No differences were observed in
      AUCs for the most discriminatory cpRNFL and macular measurements. CONCLUSION:
      Segmented macular layer analysis shows a good capacity to discriminate between
      normal and glaucomatous eyes; which is comparable to that of cpRNFL analysis in
      children with PCG.

PMID- 29643465
TI  - Sorbent Film-Coated Passive Samplers for Explosives Vapour Detection Part A:
      Materials Optimisation and Integration with Analytical Technologies.
AB  - A new thin-film passive sampler is presented as a low resource dependent and
      discrete continuous monitoring solution for explosives-related vapours. Using 15
      mid-high vapour pressure explosives-related compounds as probes, combinations of
      four thermally stable substrates and six film-based sorbents were evaluated. Meta
      aramid and phenylene oxide-based materials showed the best recoveries from small
      voids (~70%). Analysis was performed using liquid chromatography-high resolution
      accurate mass spectrometry which also enabled tentative identification of new
      targets from the acquired data. Preliminary uptake kinetics experiments revealed
      plateau concentrations on the device were reached between 3-5 days. Compounds
      used in improvised explosive devices, such as triacetone triperoxide, were
      detected within 1 hour and were stably retained by the sampler for up to 7 days.
      Sampler performance was consistent for 22 months after manufacture. Lastly, its
      direct integration with currently in-service explosives screening equipment
      including ion mobility spectrometry and thermal desorption mass spectrometry is
      presented. Following exposure to several open environments and targeted
      interferences, sampler performance was subsequently assessed and potential
      interferences identified. High-security building and area monitoring for
      concealed explosives using such cost-effective and discrete passive samplers can
      add extra assurance to search routines while minimising any additional burden on
      personnel or everyday site operation.

PMID- 29643467
TI  - Potential Orphan Drug Therapy of Intravesical Liposomal Onabotulinumtoxin-A for
      Ketamine-Induced Cystitis by Mucosal Protection and Anti-inflammation in a Rat
      Model.
AB  - Ketamine abusers may develop ulcerative cystitis and severe lower urinary tract
      symptoms, which is a medical dilemma. Recently, researchers have found the
      endemic of ketamine-induced cystitis worldwide. The intravesical administration
      of liposome-encapsulated onabotulinumtoxinA (Lipotoxin) might facilitate the
      healing of the damaged urothelium from liposomes, and reduce the urinary symptoms
      by onabotulinumtoxinA-induced chemo-denervation. Using female Sprague-Dawley
      rats, we investigated the effects of Lipotoxin on ketamine-induced cystitis.
      Functional magnetic resonance imaging, metabolic cage study, and cystometry were
      conducted. Paraffin-embedded sections were stained. The bladder mucosa and muscle
      proteins were assessed through Western blotting. We observed that repeated
      intravesical Lipotoxin instillation could improve suburothelial hemorrhage,
      recover the urothelial tight junction and adhesion proteins (zonula occludens-1
      and E-cadherin), ensure less substance P in the urothelium, inhibit the
      overexpression of inflammatory mediators (IL-6, TNF-alpha, nuclear NF-kappaB, and
      COX-2) in the detrusor, suppress the upregulation of the mucosal TRPV1 and
      detrusor M2-mAChR, and ameliorate bladder overactivity in the ketamine-treated
      rats. These data reveal the mechanisms underlying the action of Lipotoxin in
      ketamine-induced cystitis of rats, which provide a basis of Lipotoxin for further
      treating ketamine-induced cystitis in humans.

PMID- 29643466
TI  - Etidronate prevents dystrophic cardiac calcification by inhibiting macrophage
      aggregation.
AB  - Cardiovascular calcification is associated with high risk of vascular disease.
      This involves macrophage infiltration of injured vascular tissue and osteoclast
      related processes. Splenic monocytes from mice, that are predisposed (C3H) or
      resistant (B6) to calcification, were isolated and differentiated in vitro with M
      CSF to generate macrophages, which aggregate to form multinucleated (MN) cells in
      the presence of RANKL. MN cell formation was significantly decreased in monocytes
      from resistant compared with calcifying mice. Conditioned media from C3H
      macrophages strongly induced calcification in vitro. However, medium from B6
      macrophages inhibited calcification. An increase in ICAM-1 was detected in
      conditioned media from C3H macrophages compared with B6, suggesting a key role
      for this molecule in calcification processes. Due to natural genetic loss of
      Abcc6, the causal gene for cardiac calcification, C3H mice have reduced plasma
      levels of inorganic pyrophosphate (PPi), a potential calcification inhibitor.
      Supplementation of C3H mice with PPi or Etidronate prevented but did not
      completely reverse cardiac calcification. Our data provide strong evidence of the
      pathogenesis of macrophages and MNs during tissue calcification and suggest PPi
      or its analogue Etidronate as a potential inhibitor of MN formation and
      calcification. Furthermore, the adhesion molecule ICAM-1 was shown to play a key
      role in calcification.

PMID- 29643470
TI  - MRI improves diagnosis.

PMID- 29643468
TI  - A standardized flow cytometry network study for the assessment of circulating
      endothelial cell physiological ranges.
AB  - Circulating endothelial cells (CEC) represent a restricted peripheral blood (PB)
      cell subpopulation with high potential diagnostic value in many endothelium
      involving diseases. However, whereas the interest in CEC studies has grown, the
      standardization level of their detection has not. Here, we undertook the task to
      align CEC phenotypes and counts, by standardizing a novel flow cytometry
      approach, within a network of six laboratories. CEC were identified as
      alive/nucleated/CD45negative/CD34bright/CD146positive events and enumerated in
      269 healthy PB samples. Standardization was demonstrated by the achievement of
      low inter-laboratory Coefficients of Variation (CVL), calculated on the basis of
      Median Fluorescence Intensity values of the most stable antigens that allowed CEC
      identification and count (CVL of CD34bright on CEC ~ 30%; CVL of CD45 on
      Lymphocytes ~ 20%). By aggregating data acquired from all sites, CEC numbers in
      the healthy population were captured (medianfemale = 9.31 CEC/mL; medianmale =
      11.55 CEC/mL). CEC count biological variability and method specificity were
      finally assessed. Results, obtained on a large population of donors, demonstrate
      that the established procedure might be adopted as standardized method for CEC
      analysis in clinical and in research settings, providing a CEC physiological
      baseline range, useful as starting point for their clinical monitoring in
      endothelial dysfunctions.

PMID- 29643469
TI  - Snf1/AMPK is involved in the mitotic spindle alignment in Saccharomyces
      cerevisiae.
AB  - Before anaphase onset, budding yeast cells must align the mitotic spindle
      parallel to the mother-bud axis to ensure proper chromosome segregation. The
      protein kinase Snf1/AMPK is a highly conserved energy sensor, essential for
      adaptation to glucose limitation and in response to cellular stresses. However,
      recent findings indicate that it plays important functions also in non-limiting
      glucose conditions. Here we report a novel role of Snf1/AMPK in the progression
      through mitosis in glucose-repressing condition. We show that active Snf1 is
      localized to the bud neck from bud emergence to cytokinesis in a septin-dependent
      manner. In addition, loss of Snf1 induces a delay of the metaphase to anaphase
      transition that is due to a defect in the correct alignment of the mitotic
      spindle. In particular, genetic data indicate that Snf1 promotes spindle
      orientation acting in parallel with Dyn1 and in concert with Kar9. Altogether
      this study describes a new role for Snf1 in mitosis and connects cellular
      metabolism to mitosis progression.

PMID- 29643471
TI  - Current state of immunotherapy for glioblastoma.
AB  - Glioma is the most common primary cancer of the central nervous system, and
      around 50% of patients present with the most aggressive form of the disease,
      glioblastoma. Conventional therapies, including surgery, radiotherapy, and
      pharmacotherapy (typically chemotherapy with temozolomide), have not resulted in
      major improvements in the survival outcomes of patients with glioblastoma.
      Reasons for this lack of progress include invasive tumour growth in an essential
      organ, which limits the utility of local therapy, as well as the protection of
      tumour cells by the blood-brain barrier, their intrinsic resistance to the
      induction of cell death, and lack of dependence on single, targetable oncogenic
      pathways, all of which impose challenges for systemic therapy. Furthermore, the
      unique immune environment of the central nervous system needs to be considered
      when pursuing immune-based therapeutic approaches for glioblastoma. Nevertheless,
      a range of different immunotherapies are currently being actively investigated in
      patients with this disease, spurred on by advances in immuno-oncology for other
      tumour types. Herein, we examine the current state of immunotherapy for gliomas,
      notably glioblastoma, the implications for combining the current standard-of-care
      treatment modalities with immunotherapies, potential biomarkers of response, and
      future directions for glioblastoma immuno-oncology.

PMID- 29643472
TI  - High-resolution behavioral mapping of electric fishes in Amazonian habitats.
AB  - The study of animal behavior has been revolutionized by sophisticated
      methodologies that identify and track individuals in video recordings. Video
      recording of behavior, however, is challenging for many species and habitats
      including fishes that live in turbid water. Here we present a methodology for
      identifying and localizing weakly electric fishes on the centimeter scale with
      subsecond temporal resolution based solely on the electric signals generated by
      each individual. These signals are recorded with a grid of electrodes and
      analyzed using a two-part algorithm that identifies the signals from each
      individual fish and then estimates the position and orientation of each fish
      using Bayesian inference. Interestingly, because this system involves
      eavesdropping on electrocommunication signals, it permits monitoring of complex
      social and physical interactions in the wild. This approach has potential for
      large-scale non-invasive monitoring of aquatic habitats in the Amazon basin and
      other tropical freshwater systems.

PMID- 29643473
TI  - Revisiting the role of ABC transporters in multidrug-resistant cancer.
AB  - Most patients who die of cancer have disseminated disease that has become
      resistant to multiple therapeutic modalities. Ample evidence suggests that the
      expression of ATP-binding cassette (ABC) transporters, especially the multidrug
      resistance protein 1 (MDR1, also known as P-glycoprotein or P-gp), which is
      encoded by ABC subfamily B member 1 (ABCB1), can confer resistance to cytotoxic
      and targeted chemotherapy. However, the development of MDR1 as a therapeutic
      target has been unsuccessful. At the time of its discovery, appropriate tools for
      the characterization and clinical development of MDR1 as a therapeutic target
      were lacking. Thirty years after the initial cloning and characterization of MDR1
      and the implication of two additional ABC transporters, the multidrug resistance
      associated protein 1 (MRP1; encoded by ABCC1)), and ABCG2, in multidrug
      resistance, interest in investigating these transporters as therapeutic targets
      has waned. However, with the emergence of new data and advanced techniques, we
      propose to re-evaluate whether these transporters play a clinical role in
      multidrug resistance. With this Opinion article, we present recent evidence
      indicating that it is time to revisit the investigation into the role of ABC
      transporters in efficient drug delivery in various cancer types and at the blood
      brain barrier.

PMID- 29643474
TI  - Histone deacetylase 6 controls Notch3 trafficking and degradation in T-cell acute
      lymphoblastic leukemia cells.
AB  - Several studies have revealed that endosomal sorting controls the steady-state
      levels of Notch at the cell surface in normal cells and prevents its
      inappropriate activation in the absence of ligands. However, whether this highly
      dynamic physiologic process can be exploited to counteract dysregulated Notch
      signaling in cancer cells remains unknown. T-ALL is a malignancy characterized by
      aberrant Notch signaling, sustained by activating mutations in Notch1 as well as
      overexpression of Notch3, a Notch paralog physiologically subjected to lysosome
      dependent degradation in human cancer cells. Here we show that treatment with the
      pan-HDAC inhibitor Trichostatin A (TSA) strongly decreases Notch3 full-length
      protein levels in T-ALL cell lines and primary human T-ALL cells xenografted in
      mice without substantially reducing NOTCH3 mRNA levels. Moreover, TSA markedly
      reduced the levels of Notch target genes, including pTalpha, CR2, and DTX-1, and
      induced apoptosis of T-ALL cells. We further observed that Notch3 was post
      translationally regulated following TSA treatment, with reduced Notch3 surface
      levels and increased accumulation of Notch3 protein in the lysosomal compartment.
      Surface Notch3 levels were rescued by inhibition of dynein with ciliobrevin D.
      Pharmacologic studies with HDAC1, 6, and 8-specific inhibitors disclosed that
      these effects were largely due to inhibition of HDAC6 in T-ALL cells. HDAC6
      silencing by specific shRNA was followed by reduced Notch3 expression and
      increased apoptosis of T-ALL cells. Finally, HDAC6 silencing impaired leukemia
      outgrowth in mice, associated with reduction of Notch3 full-length protein in
      vivo. These results connect HDAC6 activity to regulation of total and surface
      Notch3 levels and suggest HDAC6 as a potential novel therapeutic target to lower
      Notch signaling in T-ALL and other Notch3-addicted tumors.

PMID- 29643475
TI  - Tumor-derived exosomal lnc-Sox2ot promotes EMT and stemness by acting as a ceRNA
      in pancreatic ductal adenocarcinoma.
AB  - Long noncoding RNAs (lncRNAs) or exosomes have recently been shown to play vital
      regulatory or communication roles in cancer biology. However, the roles and
      mechanisms of exosomal lncRNAs in tumor invasion or metastasis of pancreatic
      ductal adenocarcinoma (PDAC) remain unknown. In this study, we aimed to
      investigate the detailed roles and mechanisms of tumor-generated exosomes in
      progression and metastasis of PDAC in vitro and in vivo. We identified a lncRNA
      Sox2ot from exosomes of highly invasive PDAC cells, and analyzed the expression
      of Sox2ot in the plasma samples and found that the plasma exosomal Sox2ot
      expression was high and correlated with TNM stage and overall survival rate of
      PDAC patients. Further research showed that Sox2ot promotes epithelial
      mesenchymal transition (EMT) and stem cell like properties by regulating Sox2
      expression. Sox2ot competitively binds to the miR-200 family to regulate the
      expression of Sox2, thus promoting invasion and metastasis of PDAC. We also
      confirmed the transmission of the exosomes from producer cells to recipient PDAC
      cells, exosomal Sox2ot can promote tumor invasion and metastasis in vitro and in
      vivo. We further confirmed tumor generated exosomes could excrete to tumor cell
      or blood circulation in vivo condition. Finally, we observed a decreased exosomal
      Sox2ot expression in postoperative blood samples of PDAC patients. The exosomal
      lncRNA Sox2ot plays important roles in tumor progression and may be a useful
      maker for pancreatic cancer prognosis.

PMID- 29643476
TI  - Inhibition of ovarian tumor cell invasiveness by targeting SYK in the tyrosine
      kinase signaling pathway.
AB  - Cell motility and invasiveness are prerequisites for dissemination, and largely
      account for cancer mortality. We have identified an actionable kinase, spleen
      tyrosine kinase (SYK), which is keenly tightly associated with tumor progression
      in ovarian cancer. Here, we report that active recombinant SYK directly
      phosphorylates cortactin and cofilin, which are critically involved in assembly
      and dynamics of actin filament through phosphorylation signaling. Enhancing SYK
      activity by inducing expression of a constitutively active SYK mutant, SYK130E,
      increased growth factor-stimulated migration and invasion of ovarian cancer
      cells, which was abrogated by cortactin knockdown. Similarly, SYK inhibitors
      significantly decreased invasion of ovarian cancer cells across basement membrane
      in real-time transwell assays and in 3D tumor spheroid models. SYK inactivation
      by targeted gene knockout or by small molecule inhibition reduced actin
      polymerization. Collectively, this study reported a new mechanism by which SYK
      signaling regulates ovarian cancer cell motility and invasiveness, and suggest a
      target-based strategy to prevent or suppress the advancement of ovarian
      malignancies.

PMID- 29643477
TI  - Accurate estimation of 5-methylcytosine in mammalian mitochondrial DNA.
AB  - Whilst 5-methylcytosine (5mC) is a major epigenetic mark in the nuclear DNA in
      mammals, whether or not mitochondrial DNA (mtDNA) receives 5mC modification
      remains controversial. Herein, we exhaustively analysed mouse mtDNA using three
      methods that are based upon different principles for detecting 5mC. Next
      generation bisulfite sequencing did not give any significant signatures of
      methylation in mtDNAs of liver, brain and embryonic stem cells (ESCs). Also,
      treatment with methylated cytosine-sensitive endonuclease McrBC resulted in no
      substantial decrease of mtDNA band intensities in Southern hybridisation.
      Furthermore, mass spectrometric nucleoside analyses of highly purified liver
      mtDNA preparations did not detect 5-methyldeoxycytidine at the levels found in
      the nuclear DNA but at a range of only 0.3-0.5% of deoxycytidine. Taken together,
      we propose that 5mC is not present at any specific region(s) of mtDNA and that
      levels of the methylated cytosine are fairly low, provided the modification
      occurs. It is thus unlikely that 5mC plays a universal role in mtDNA gene
      expression or mitochondrial metabolism.

PMID- 29643478
TI  - Mucin gel assembly is controlled by a collective action of non-mucin proteins,
      disulfide bridges, Ca2+-mediated links, and hydrogen bonding.
AB  - Mucus is characterized by multiple levels of assembly at different length scales
      which result in a unique set of rheological (flow) and mechanical properties.
      These physical properties determine its biological function as a highly selective
      barrier for transport of water and nutrients, while blocking penetration of
      pathogens and foreign particles. Altered integrity of the mucus layer in the
      small intestine has been associated with a number of gastrointestinal tract
      pathologies such as Crohn's disease and cystic fibrosis. In this work, we uncover
      an intricate hierarchy of intestinal mucin (Muc2) assembly and show how complex
      rheological properties emerge from synergistic interactions between mucin
      glycoproteins, non-mucin proteins, and Ca2+. Using a novel method of mucus
      purification, we demonstrate the mechanism of assembly of Muc2 oligomers into
      viscoelastic microscale domains formed via hydrogen bonding and Ca2+-mediated
      links, which require the joint presence of Ca2+ ions and non-mucin proteins.
      These microscale domains aggregate to form a heterogeneous yield stress gel-like
      fluid, the macroscopic rheological properties of which are virtually identical to
      that of native intestinal mucus. Through proteomic analysis, we short-list
      potential protein candidates implicated in mucin assembly, thus paving the way
      for identifying the molecules responsible for the physiologically critical
      biophysical properties of mucus.

PMID- 29643480
TI  - The basal ganglia and the cerebellum: nodes in an integrated network.
AB  - The basal ganglia and the cerebellum are considered to be distinct subcortical
      systems that perform unique functional operations. The outputs of the basal
      ganglia and the cerebellum influence many of the same cortical areas but do so by
      projecting to distinct thalamic nuclei. As a consequence, the two subcortical
      systems were thought to be independent and to communicate only at the level of
      the cerebral cortex. Here, we review recent data showing that the basal ganglia
      and the cerebellum are interconnected at the subcortical level. The subthalamic
      nucleus in the basal ganglia is the source of a dense disynaptic projection to
      the cerebellar cortex. Similarly, the dentate nucleus in the cerebellum is the
      source of a dense disynaptic projection to the striatum. These observations lead
      to a new functional perspective that the basal ganglia, the cerebellum and the
      cerebral cortex form an integrated network. This network is topographically
      organized so that the motor, cognitive and affective territories of each node in
      the network are interconnected. This perspective explains how synaptic
      modifications or abnormal activity at one node can have network-wide effects. A
      future challenge is to define how the unique learning mechanisms at each network
      node interact to improve performance.

PMID- 29643481
TI  - Bruno Kyewski 1950-2018.

PMID- 29643479
TI  - Use of statins and the risk of dementia and mild cognitive impairment: A
      systematic review and meta-analysis.
AB  - We conducted a systematic review and meta-analysis to investigate whether the use
      of statins could be associated with the risk of all-caused dementia, Alzheimer's
      disease (AD), vascular dementia (VaD), and mild cognitive impairment (MCI). Major
      electronic databases were searched until December 27th, 2017 for studies
      investigating use of statins and incident cognitive decline in adults. Random
      effects meta-analyses calculating relative risks (RRs) were conducted to
      synthesize effect sizes of individual studies. Twenty-five studies met
      eligibility criteria. Use of statins was significantly associated with a reduced
      risk of all-caused dementia (k = 16 studies, adjusted RR (aRR) = 0.849, 95% CI =
      0.787-0.916, p = 0.000), AD (k = 14, aRR = 0.719, 95% CI = 0.576-0.899, p =
      0.004), and MCI (k = 6, aRR = 0.737, 95% CI = 0.556-0.976, p = 0.033), but no
      meaningful effects on incident VaD (k = 3, aRR = 1.012, 95% CI = 0.620-1.652, p =
      0.961). Subgroup analysis suggested that hydrophilic statins were associated with
      reduced risk of all-caused dementia (aRR = 0.877; CI = 0.818-0.940; p = 0.000)
      and possibly lower AD risk (aRR = 0.619; CI = 0.383-1.000; p = 0.050). Lipophilic
      statins were associated with reduced risk of AD (aRR = 0.639; CI = 0.449-0.908; p
      = 0.013) but not all-caused dementia (aRR = 0.738; CI = 0.475-1.146; p = 0.176).
      In conclusion, our meta-analysis suggests that the use of statins may reduce the
      risk of all-type dementia, AD, and MCI, but not of incident VaD.

PMID- 29643482
TI  - Reversible Mn2+/Mn4+ double redox in lithium-excess cathode materials.
AB  - There is an urgent need for low-cost, resource-friendly, high-energy-density
      cathode materials for lithium-ion batteries to satisfy the rapidly increasing
      need for electrical energy storage. To replace the nickel and cobalt, which are
      limited resources and are associated with safety problems, in current lithium-ion
      batteries, high-capacity cathodes based on manganese would be particularly
      desirable owing to the low cost and high abundance of the metal, and the
      intrinsic stability of the Mn4+ oxidation state. Here we present a strategy of
      combining high-valent cations and the partial substitution of fluorine for oxygen
      in a disordered-rocksalt structure to incorporate the reversible Mn2+/Mn4+ double
      redox couple into lithium-excess cathode materials. The lithium-rich cathodes
      thus produced have high capacity and energy density. The use of the Mn2+/Mn4+
      redox reduces oxygen redox activity, thereby stabilizing the materials, and opens
      up new opportunities for the design of high-performance manganese-rich cathodes
      for advanced lithium-ion batteries.

PMID- 29643483
TI  - Alteration of the magnetosphere of the Vela pulsar during a glitch.
AB  - As pulsars lose energy, primarily in the form of magnetic dipole radiation, their
      rotation slows down accordingly. For some pulsars, this spin-down is interrupted
      by occasional abrupt spin-up events known as glitches 1 . A glitch is
      hypothesized to be a catastrophic release of pinned vorticity 2 that provides an
      exchange of angular momentum between the superfluid outer core and the crust.
      This is manifested by a minute alteration in the rotation rate of the neutron
      star and its co-rotating magnetosphere, which is revealed by an abrupt change in
      the timing of observed radio pulses. Measurement of the flux density,
      polarization and single-pulse arrival times of the glitch with high time
      resolution may reveal the equation of state of the crustal superfluid, its drag
      to-lift ratio and the parameters that describe its friction with the crust 3 .
      This has not hitherto been possible because glitch events happen unpredictably.
      Here we report single-pulse radio observations of a glitch in the Vela pulsar,
      which has a rotation frequency of 11.2 hertz. The glitch was detected on 2016
      December 12 at 11:36 universal time, during continuous observations of the pulsar
      over a period of three years. We detected sudden changes in the pulse shape
      coincident with the glitch event: one pulse was unusually broad, the next pulse
      was missing (a 'null') and the following two pulses had unexpectedly low linear
      polarization. This sequence was followed by a 2.6-second interval during which
      pulses arrived later than usual, indicating that the glitch affects the
      magnetosphere.

PMID- 29643484
TI  - Anomalously weak Labrador Sea convection and Atlantic overturning during the past
      150 years.
AB  - The Atlantic meridional overturning circulation (AMOC) is a system of ocean
      currents that has an essential role in Earth's climate, redistributing heat and
      influencing the carbon cycle1, 2. The AMOC has been shown to be weakening in
      recent years 1 ; this decline may reflect decadal-scale variability in convection
      in the Labrador Sea, but short observational datasets preclude a longer-term
      perspective on the modern state and variability of Labrador Sea convection and
      the AMOC1, 3-5. Here we provide several lines of palaeo-oceanographic evidence
      that Labrador Sea deep convection and the AMOC have been anomalously weak over
      the past 150 years or so (since the end of the Little Ice Age, LIA, approximately
      AD 1850) compared with the preceding 1,500 years. Our palaeoclimate
      reconstructions indicate that the transition occurred either as a predominantly
      abrupt shift towards the end of the LIA, or as a more gradual, continued decline
      over the past 150 years; this ambiguity probably arises from non-AMOC influences
      on the various proxies or from the different sensitivities of these proxies to
      individual components of the AMOC. We suggest that enhanced freshwater fluxes
      from the Arctic and Nordic seas towards the end of the LIA-sourced from melting
      glaciers and thickened sea ice that developed earlier in the LIA-weakened
      Labrador Sea convection and the AMOC. The lack of a subsequent recovery may have
      resulted from hysteresis or from twentieth-century melting of the Greenland Ice
      Sheet 6 . Our results suggest that recent decadal variability in Labrador Sea
      convection and the AMOC has occurred during an atypical, weak background state.
      Future work should aim to constrain the roles of internal climate variability and
      early anthropogenic forcing in the AMOC weakening described here.

PMID- 29643485
TI  - Observed fingerprint of a weakening Atlantic Ocean overturning circulation.
AB  - The Atlantic meridional overturning circulation (AMOC)-a system of ocean currents
      in the North Atlantic-has a major impact on climate, yet its evolution during the
      industrial era is poorly known owing to a lack of direct current measurements.
      Here we provide evidence for a weakening of the AMOC by about 3 +/- 1 sverdrups
      (around 15 per cent) since the mid-twentieth century. This weakening is revealed
      by a characteristic spatial and seasonal sea-surface temperature 'fingerprint'
      consisting of a pattern of cooling in the subpolar Atlantic Ocean and warming in
      the Gulf Stream region-and is calibrated through an ensemble of model simulations
      from the CMIP5 project. We find this fingerprint both in a high-resolution
      climate model in response to increasing atmospheric carbon dioxide
      concentrations, and in the temperature trends observed since the late nineteenth
      century. The pattern can be explained by a slowdown in the AMOC and reduced
      northward heat transport, as well as an associated northward shift of the Gulf
      Stream. Comparisons with recent direct measurements from the RAPID project and
      several other studies provide a consistent depiction of record-low AMOC values in
      recent years.

PMID- 29643486
TI  - Experimentally generated randomness certified by the impossibility of
      superluminal signals.
AB  - From dice to modern electronic circuits, there have been many attempts to build
      better devices to generate random numbers. Randomness is fundamental to security
      and cryptographic systems and to safeguarding privacy. A key challenge with
      random-number generators is that it is hard to ensure that their outputs are
      unpredictable1-3. For a random-number generator based on a physical process, such
      as a noisy classical system or an elementary quantum measurement, a detailed
      model that describes the underlying physics is necessary to assert
      unpredictability. Imperfections in the model compromise the integrity of the
      device. However, it is possible to exploit the phenomenon of quantum non-locality
      with a loophole-free Bell test to build a random-number generator that can
      produce output that is unpredictable to any adversary that is limited only by
      general physical principles, such as special relativity1-11. With recent
      technological developments, it is now possible to carry out such a loophole-free
      Bell test12-14,22. Here we present certified randomness obtained from a photonic
      Bell experiment and extract 1,024 random bits that are uniformly distributed to
      within 10-12. These random bits could not have been predicted according to any
      physical theory that prohibits faster-than-light (superluminal) signalling and
      that allows independent measurement choices. To certify and quantify the
      randomness, we describe a protocol that is optimized for devices that are
      characterized by a low per-trial violation of Bell inequalities. Future random
      number generators based on loophole-free Bell tests may have a role in increasing
      the security and trust of our cryptographic systems and infrastructure.

PMID- 29643487
TI  - Outsourcing is in.

PMID- 29643489
TI  - How gravitational waves might help fundamental cosmology.

PMID- 29643490
TI  - Ocean circulation is changing, and we need to know why.

PMID- 29643492
TI  - Take a holistic view when making pesticide policies stricter.

PMID- 29643493
TI  - Build two-way rapport for better policymaking.

PMID- 29643494
TI  - Save a North Sea fish from becoming museum piece.

PMID- 29643495
TI  - Don't dismiss citations to journals not published in English.

PMID- 29643497
TI  - Curtail climate-change effects using Singapore Index of Cities' Biodiversity.

PMID- 29643499
TI  - Suspected chemical attack, opioid-crisis cash and nuclear-fusion facility.

PMID- 29643498
TI  - How gravitational waves could solve some of the Universe's deepest mysteries.

PMID- 29643501
TI  - Prostate cancer and social media.
AB  - The use of social media is increasing globally and is employed in a variety of
      ways in the prostate cancer community. In addition to their use in research,
      advocacy, and awareness campaigns, social media offer vast opportunities for
      education and networking for patients with prostate cancer and health-care
      professionals, and many educational resources and support networks are available
      to patients with prostate cancer and their caregivers. Despite the considerable
      potential for social media to be employed in the field of prostate cancer,
      concerns remain - particularly regarding the maintenance of patient
      confidentiality, variable information quality, and possible financial conflicts
      of interest. A number of professional societies have, therefore, issued guidance
      regarding social media use in medicine. Social media are used extensively in
      other cancer communities, particularly among patients with breast cancer, and
      both the quantity and type of information available are expected to grow in the
      future.

PMID- 29643500
TI  - Impact of a vegan diet on the human salivary microbiota.
AB  - Little is known about the effect of long-term diet patterns on the composition
      and functional potential of the human salivary microbiota. In the present study,
      we sought to contribute to the ongoing elucidation of dietary effects on the oral
      microbial community by examining the diversity, composition and functional
      potential of the salivary microbiota in 160 healthy vegans and omnivores using
      16S rRNA gene amplicon sequencing. We further sought to identify bacterial taxa
      in saliva associated with host inflammatory markers. We show that compositional
      differences in the salivary microbiota of vegans and omnivores is present at all
      taxonomic levels below phylum level and includes upper respiratory tract
      commensals (e.g. Neisseria subflava, Haemophilus parainfluenzae, and Rothia
      mucilaginosa) and species associated with periodontal disease (e.g. Campylobacter
      rectus and Porphyromonas endodontalis). Dietary intake of medium chain fatty
      acids, piscine mono- and polyunsaturated fatty acids, and dietary fibre was
      associated with bacterial diversity, community structure, as well as relative
      abundance of several species-level operational taxonomic units. Analysis of
      imputed genomic potential revealed several metabolic pathways differentially
      abundant in vegans and omnivores indicating possible effects of macro- and micro
      nutrient intake. We also show that certain oral bacteria are associated with the
      systemic inflammatory state of the host.

PMID- 29643502
TI  - Unravelling disparate roles of NOTCH in bladder cancer.
AB  - The Notch pathway has been implicated in both oncogenic and tumour-suppressive
      roles in cancer depending on the tissue type and cellular context. However, until
      recently, little was known about the pathway in bladder cancer. Studies have
      revealed that NOTCH1 copy number and expression are decreased in bladder cancer
      and NOTCH1 activation in bladder cancer cell lines reduces proliferation,
      suggesting that NOTCH1 acts as a tumour suppressor. Furthermore, in transgenic
      models, bladder cancer is promoted by bladder-specific inactivation of a
      component of the gamma-secretase complex, which liberates the intracellular
      domain of neurogenic locus Notch homologue protein (NOTCH) and starts the
      signalling cascade. By contrast, further work has demonstrated that NOTCH2 acts
      as an oncogene that promotes cell proliferation and metastasis through epithelial
      to-mesenchymal transition, cell cycle progression, and maintenance of stemness.
      Studies indicating that NOTCH1 and NOTCH2 have opposite effects on the
      progression of bladder cancer could give rise to potential therapeutic approaches
      aimed at blocking or restoring the Notch pathway.

PMID- 29643503
TI  - Functional circuit architecture underlying parental behaviour.
AB  - Parenting is essential for the survival and wellbeing of mammalian offspring.
      However, we lack a circuit-level understanding of how distinct components of this
      behaviour are coordinated. Here we investigate how galanin-expressing neurons in
      the medial preoptic area (MPOAGal) of the hypothalamus coordinate motor,
      motivational, hormonal and social aspects of parenting in mice. These neurons
      integrate inputs from a large number of brain areas and the activation of these
      inputs depends on the animal's sex and reproductive state. Subsets of MPOAGal
      neurons form discrete pools that are defined by their projection sites. While the
      MPOAGal population is active during all episodes of parental behaviour,
      individual pools are tuned to characteristic aspects of parenting. Optogenetic
      manipulation of MPOAGal projections mirrors this specificity, affecting discrete
      parenting components. This functional organization, reminiscent of the control of
      motor sequences by pools of spinal cord neurons, provides a new model for how
      discrete elements of a social behaviour are generated at the circuit level.

PMID- 29643504
TI  - Genome evolution across 1,011 Saccharomyces cerevisiae isolates.
AB  - Large-scale population genomic surveys are essential to explore the phenotypic
      diversity of natural populations. Here we report the whole-genome sequencing and
      phenotyping of 1,011 Saccharomyces cerevisiae isolates, which together provide an
      accurate evolutionary picture of the genomic variants that shape the species-wide
      phenotypic landscape of this yeast. Genomic analyses support a single 'out-of
      China' origin for this species, followed by several independent domestication
      events. Although domesticated isolates exhibit high variation in ploidy,
      aneuploidy and genome content, genome evolution in wild isolates is mainly driven
      by the accumulation of single nucleotide polymorphisms. A common feature is the
      extensive loss of heterozygosity, which represents an essential source of inter
      individual variation in this mainly asexual species. Most of the single
      nucleotide polymorphisms, including experimentally identified functional
      polymorphisms, are present at very low frequencies. The largest numbers of
      variants identified by genome-wide association are copy-number changes, which
      have a greater phenotypic effect than do single nucleotide polymorphisms. This
      resource will guide future population genomics and genotype-phenotype studies in
      this classic model system.

PMID- 29643505
TI  - High male sexual investment as a driver of extinction in fossil ostracods.
AB  - Sexual selection favours traits that confer advantages in the competition for
      mates. In many cases, such traits are costly to produce and maintain, because the
      costs help to enforce the honesty of these signals and cues 1 . Some evolutionary
      models predict that sexual selection also produces costs at the population level,
      which could limit the ability of populations to adapt to changing conditions and
      thus increase the risk of extinction2-4. Other models, however, suggest that
      sexual selection should increase rates of adaptation and enhance the removal of
      deleterious mutations, thus protecting populations against extinction3, 5, 6.
      Resolving the conflict between these models is not only important for explaining
      the history of biodiversity, but also relevant to understanding the mechanisms of
      the current biodiversity crisis. Previous attempts to test the conflicting
      predictions produced by these models have been limited to extant species and have
      thus relied on indirect proxies for species extinction. Here we use the
      informative fossil record of cytheroid ostracods-small, bivalved crustaceans with
      sexually dimorphic carapaces-to test how sexual selection relates to actual
      species extinction. We show that species with more pronounced sexual dimorphism,
      indicating the highest levels of male investment in reproduction, had estimated
      extinction rates that were ten times higher than those of the species with the
      lowest investment. These results indicate that sexual selection can be a
      substantial risk factor for extinction.

PMID- 29643506
TI  - Structure and regulation of the human INO80-nucleosome complex.
AB  - Access to DNA within nucleosomes is required for a variety of processes in cells
      including transcription, replication and repair. Consequently, cells encode
      multiple systems that remodel nucleosomes. These complexes can be simple,
      involving one or a few protein subunits, or more complicated multi-subunit
      machines 1 . Biochemical studies2-4 have placed the motor domains of several
      chromatin remodellers in the superhelical location 2 region of the nucleosome.
      Structural studies of yeast Chd1 and Snf2-a subunit in the complex with the
      capacity to remodel the structure of chromatin (RSC)-in complex with nucleosomes5
      7 have provided insights into the basic mechanism of nucleosome sliding performed
      by these complexes. However, how larger, multi-subunit remodelling complexes such
      as INO80 interact with nucleosomes and how remodellers carry out functions such
      as nucleosome sliding 8 , histone exchange 9 and nucleosome spacing10-12 remain
      poorly understood. Although some remodellers work as monomers 13 , others work as
      highly cooperative dimers11, 14, 15. Here we present the structure of the human
      INO80 chromatin remodeller with a bound nucleosome, which reveals that INO80
      interacts with nucleosomes in a previously undescribed manner: the motor domains
      are located on the DNA at the entry point to the nucleosome, rather than at
      superhelical location 2. The ARP5-IES6 module of INO80 makes additional contacts
      on the opposite side of the nucleosome. This arrangement enables the histone H3
      tails of the nucleosome to have a role in the regulation of the activities of the
      INO80 motor domain-unlike in other characterized remodellers, for which H4 tails
      have been shown to regulate the motor domains.

PMID- 29643507
TI  - An evolutionarily conserved ribosome-rescue pathway maintains epidermal
      homeostasis.
AB  - Ribosome-associated mRNA quality control mechanisms ensure the fidelity of
      protein translation1,2. Although these mechanisms have been extensively studied
      in yeast, little is known about their role in mammalian tissues, despite emerging
      evidence that stem cell fate is controlled by translational mechanisms3,4. One
      evolutionarily conserved component of the quality control machinery, Dom34 (in
      higher eukaryotes known as Pelota (Pelo)), rescues stalled ribosomes 5 . Here we
      show that Pelo is required for mammalian epidermal homeostasis. Conditional
      deletion of Pelo in mouse epidermal stem cells that express Lrig1 results in
      hyperproliferation and abnormal differentiation of these cells. By contrast,
      deletion of Pelo in Lgr5-expressing stem cells has no effect and deletion in Lgr6
      expressing stem cells induces only a mild phenotype. Loss of Pelo results in
      accumulation of short ribosome footprints and global upregulation of translation,
      rather than affecting the expression of specific genes. Translational inhibition
      by rapamycin-mediated downregulation of mTOR (mechanistic target of rapamycin
      kinase) rescues the epidermal phenotype. Our study reveals that the ribosome
      rescue machinery is important for mammalian tissue homeostasis and that it has
      specific effects on different stem cell populations.

PMID- 29643508
TI  - Aspm knockout ferret reveals an evolutionary mechanism governing cerebral
      cortical size.
AB  - The human cerebral cortex is distinguished by its large size and abundant
      gyrification, or folding. However, the evolutionary mechanisms that drive
      cortical size and structure are unknown. Although genes that are essential for
      cortical developmental expansion have been identified from the genetics of human
      primary microcephaly (a disorder associated with reduced brain size and
      intellectual disability) 1 , studies of these genes in mice, which have a smooth
      cortex that is one thousand times smaller than the cortex of humans, have
      provided limited insight. Mutations in abnormal spindle-like microcephaly
      associated (ASPM), the most common recessive microcephaly gene, reduce cortical
      volume by at least 50% in humans2-4, but have little effect on the brains of
      mice5-9; this probably reflects evolutionarily divergent functions of ASPM10,11.
      Here we used genome editing to create a germline knockout of Aspm in the ferret
      (Mustela putorius furo), a species with a larger, gyrified cortex and greater
      neural progenitor cell diversity12-14 than mice, and closer protein sequence
      homology to the human ASPM protein. Aspm knockout ferrets exhibit severe
      microcephaly (25-40% decreases in brain weight), reflecting reduced cortical
      surface area without significant change in cortical thickness, as has been found
      in human patients3,4, suggesting that loss of 'cortical units' has occurred. The
      cortex of fetal Aspm knockout ferrets displays a very large premature
      displacement of ventricular radial glial cells to the outer subventricular zone,
      where many resemble outer radial glia, a subtype of neural progenitor cells that
      are essentially absent in mice and have been implicated in cerebral cortical
      expansion in primates12-16. These data suggest an evolutionary mechanism by which
      ASPM regulates cortical expansion by controlling the affinity of ventricular
      radial glial cells for the ventricular surface, thus modulating the ratio of
      ventricular radial glial cells, the most undifferentiated cell type, to outer
      radial glia, a more differentiated progenitor.

PMID- 29643510
TI  - Intra-tumour diversification in colorectal cancer at the single-cell level.
AB  - Every cancer originates from a single cell. During expansion of the neoplastic
      cell population, individual cells acquire genetic and phenotypic differences from
      each other. Here, to investigate the nature and extent of intra-tumour
      diversification, we characterized organoids derived from multiple single cells
      from three colorectal cancers as well as from adjacent normal intestinal crypts.
      Colorectal cancer cells showed extensive mutational diversification and carried
      several times more somatic mutations than normal colorectal cells. Most mutations
      were acquired during the final dominant clonal expansion of the cancer and
      resulted from mutational processes that are absent from normal colorectal cells.
      Intra-tumour diversification of DNA methylation and transcriptome states also
      occurred; these alterations were cell-autonomous, stable, and followed the
      phylogenetic tree of each cancer. There were marked differences in responses to
      anticancer drugs between even closely related cells of the same tumour. The
      results indicate that colorectal cancer cells experience substantial increases in
      somatic mutation rate compared to normal colorectal cells, and that genetic
      diversification of each cancer is accompanied by pervasive, stable and inherited
      differences in the biological states of individual cancer cells.

PMID- 29643509
TI  - Structural basis for ATP-dependent chromatin remodelling by the INO80 complex.
AB  - In the eukaryotic nucleus, DNA is packaged in the form of nucleosomes, each of
      which comprises about 147 base pairs of DNA wrapped around a histone protein
      octamer. The position and histone composition of nucleosomes is governed by ATP
      dependent chromatin remodellers1-3 such as the 15-subunit INO80 complex 4 . INO80
      regulates gene expression, DNA repair and replication by sliding nucleosomes, the
      exchange of histone H2A.Z with H2A, and the positioning of + 1 and -1 nucleosomes
      at promoter DNA5-8. The structures and mechanisms of these remodelling reactions
      are currently unknown. Here we report the cryo-electron microscopy structure of
      the evolutionarily conserved core of the INO80 complex from the fungus Chaetomium
      thermophilum bound to a nucleosome, at a global resolution of 4.3 A and with
      major parts at 3.7 A. The INO80 core cradles one entire gyre of the nucleosome
      through multivalent DNA and histone contacts. An Rvb1/Rvb2 AAA+ ATPase
      heterohexamer is an assembly scaffold for the complex and acts as a 'stator' for
      the motor and nucleosome-gripping subunits. The Swi2/Snf2 ATPase motor binds to
      nucleosomal DNA at superhelical location -6, unwraps approximately 15 base pairs,
      disrupts the H2A-DNA contacts and is poised to pump entry DNA into the
      nucleosome. Arp5 and Ies6 bind superhelical locations -2 and -3 to act as a
      counter grip for the motor, on the other side of the H2A-H2B dimer. The Arp5
      insertion domain forms a grappler element that binds the nucleosome dyad,
      connects the Arp5 actin-fold and entry DNA over a distance of about 90 A and
      packs against histone H2A-H2B near the 'acidic patch'. Our structure together
      with biochemical data 8 suggests a unified mechanism for nucleosome sliding and
      histone editing by INO80. The motor is part of a macromolecular ratchet,
      persistently pumping entry DNA across the H2A-H2B dimer against the Arp5 grip
      until a large nucleosome translocation step occurs. The transient exposure of H2A
      H2B by motor activity as well as differential recognition of H2A.Z and H2A may
      regulate histone exchange.

PMID- 29643511
TI  - Activity-based E3 ligase profiling uncovers an E3 ligase with esterification
      activity.
AB  - Ubiquitination is initiated by transfer of ubiquitin (Ub) from a ubiquitin
      activating enzyme (E1) to a ubiquitin-conjugating enzyme (E2), producing a
      covalently linked intermediate (E2-Ub) 1 . Ubiquitin ligases (E3s) of the 'really
      interesting new gene' (RING) class recruit E2-Ub via their RING domain and then
      mediate direct transfer of ubiquitin to substrates 2 . By contrast, 'homologous
      to E6-AP carboxy terminus' (HECT) E3 ligases undergo a catalytic cysteine
      dependent transthiolation reaction with E2-Ub, forming a covalent E3-Ub
      intermediate3,4. Additionally, RING-between-RING (RBR) E3 ligases have a
      canonical RING domain that is linked to an ancillary domain. This ancillary
      domain contains a catalytic cysteine that enables a hybrid RING-HECT mechanism 5
      . Ubiquitination is typically considered a post-translational modification of
      lysine residues, as there are no known human E3 ligases with non-lysine activity.
      Here we perform activity-based protein profiling of HECT or RBR-like E3 ligases
      and identify the neuron-associated E3 ligase MYCBP2 (also known as PHR1) as the
      apparent single member of a class of RING-linked E3 ligase with esterification
      activity and intrinsic selectivity for threonine over serine. MYCBP2 contains two
      essential catalytic cysteine residues that relay ubiquitin to its substrate via
      thioester intermediates. Crystallographic characterization of this class of E3
      ligase, which we designate RING-Cys-relay (RCR), provides insights into its
      mechanism and threonine selectivity. These findings implicate non-lysine
      ubiquitination in cellular regulation of higher eukaryotes and suggest that E3
      enzymes have an unappreciated mechanistic diversity.

PMID- 29643513
TI  - Finding IRESs in mycoviruses.

PMID- 29643514
TI  - Blasting through cells.

PMID- 29643515
TI  - [Role of aquaporin-4 in the change of interstitial fluid drainage in Alzheimer's
      disease].
AB  - OBJECTIVE: To observe the characteristics of the interstitial fluid (ISF)
      drainage in the Alzheimer's disease (AD) rats through magnetic resonance imaging
      (MRI) tracer gadolinium-diethylene triamine pentacetic acid (Gd-DTPA)spread in
      the brain extracellular space (ECS) and to discuss the role of aquaporin-4 (Aqp4)
      in the AD. METHODS: Wild type SD rats (300-350 g) and Aqp4 gene knock out (Aqp4-/
      ) SD rats (300-350g) were divided into Sham group, AD group, Aqp4-/--Sham group
      and Aqp4-/--AD group. Sham group and Aqp4-/--Sham group were injected with saline
      by intraperitoneal each day for 6 weeks, and the AD group and Aqp4-/--AD group
      were injected with D-galactose by intraperitoneal each day for 6 weeks. MRI
      tracer Gd-DTPA (10 mmol/L, 2 MUL) was injected into the hippocampus of the rats.
      MRI scan was performed at the end of 0.5 h, 1.5 h, 1 h, 2 h, and 3 h to observe
      the dynamic distribution of the Gd-DTPA in the hippocampus and the diffusion rate
      D*, clearance rate k' and half-life t1/2 measured. RESULTS: The diffusion rate D*
      in Sham group was (2.66+/-0.36)*10-6 mm2/s, the diffusion rate D* in AD group was
      (2.72+/-0.62)*10-6 mm2/s, the diffusion rate D* in Aqp4-/--Sham group was (2.75+/
      0.47)*10-6 mm2/s, the diffusion rate D* in Aqp4-/--AD group was (2.802+/-0.55)*10
      6 mm2/s, and there was no statistically significant difference in the four groups
      (One-Way ANOVA, P>0.05).The clearance rate k' in Sham group was (4.57+/-0.14)*10
      4/s, the clearance rate k' in AD group was (3.68+/-0.22)*10-4/s, the clearance
      rate k' in Aqp4-/--Sham group was (3.17+/-0.16)*10-4/s, the clearance rate k' in
      Aqp4-/--AD group was (2.59+/-0.19)*10-4/s, and there was significant difference
      in the four groups (One-Way ANOVA, P<0.05). The half-life t1/2 in Sham group was
      (0.67+/-0.12) h, the half-life t1/2 in AD group was (0.88+/-0.08) h, the half
      life t1/2 in Aqp4-/--Sham group was (1.12+/-0.15) h, the half-life t1/2 in Aqp4-/
      -AD group was (1.58+/-0.11) h, and there was significance difference in the four
      groups(one-way ANOVA,P<0.05). CONCLUSION: The ISF drainage is slow after AD and
      the loss of Aqp4 in the AD makes the ISF drainage obviously slow down, Aqp4 plays
      an important role in AD to remove the metabolism of waste out of the brain.

PMID- 29643512
TI  - Innate immune memory in the brain shapes neurological disease hallmarks.
AB  - Innate immune memory is a vital mechanism of myeloid cell plasticity that occurs
      in response to environmental stimuli and alters subsequent immune responses. Two
      types of immunological imprinting can be distinguished-training and tolerance.
      These are epigenetically mediated and enhance or suppress subsequent
      inflammation, respectively. Whether immune memory occurs in tissue-resident
      macrophages in vivo and how it may affect pathology remains largely unknown. Here
      we demonstrate that peripherally applied inflammatory stimuli induce acute immune
      training and tolerance in the brain and lead to differential epigenetic
      reprogramming of brain-resident macrophages (microglia) that persists for at
      least six months. Strikingly, in a mouse model of Alzheimer's pathology, immune
      training exacerbates cerebral beta-amyloidosis and immune tolerance alleviates
      it; similarly, peripheral immune stimulation modifies pathological features after
      stroke. Our results identify immune memory in the brain as an important modifier
      of neuropathology.

PMID- 29643516
TI  - [Preliminary study of robot-assisted ankle rehabilitation for children with
      cerebral palsy].
AB  - OBJECTIVE: To propose a kind of robotic ankle-foot rehabilitation system for
      children with cerebral palsy and to preliminarily verify its feasibility in
      clinical application. METHODS: A robot assisted ankle-foot rehabilitation system
      was specially designed and developed for children with cerebral palsy and a
      preliminary clinical study was conducted in Department of Rehabilitation
      Medicine, Peking University First Hospital. Modified Tardieu Scale and joint
      biomechanical properties (ankle plantar flexion resistance torque under different
      ankle dorsiflexion angles) were measured to analyze the muscle tone and soft
      tissue compliance of the ankle plantar flexors pre- and post-robotic training
      intervention. Six children with cerebral palsy (4 girls and 2 boys, mean age: 7
      years) were recruited in this study. Each subject received 5 session robotic
      training and each session included 10-cycle passive stretching and static hold.
      SPSS 19.0 software was used for data statistical analysis. RESULTS: Both R1 and
      R2 angles of Modified Tardieu Scale for ankle plantar flexors after training were
      significantly higher than those before the treatments (Gastrocnemius: PR1=0.003,
      PR2=0.029; Soleus: PR1=0.002, PR2=0.034). The difference between R2 and R1 was of
      no statistical difference before and after the training (P=0.067 and P=0.067,
      respectively). After training, the ankle plantar flexion resistance torque under
      different dorsiflexion angles (0 degrees , 10 degrees , 20 degrees , 30 degrees )
      were significantly reduced than those before training (P=0.001, P=0.001, P=0.014,
      P=0.002, respectively). CONCLUSION: The robot assisted ankle-foot rehabilitation
      system can improve the contracture and soft tissue compliance of cerebral palsy
      children's ankle plantar flexors. All the children in the study were well
      tolerated and interested with the training, easy to accept and cooperate with it.
      This device may be suitable for application in the rehabilitation of children
      with cerebral palsy. However, further randomized clinical trials with larger
      sample size are still needed to verify the long term efficacy of this device.

PMID- 29643517
TI  - [Application of scalp-recorded high-frequency oscillations in epileptic
      encephalopathy with continuous spike-and-wave during sleep].
AB  - OBJECTIVE: To investigate the clinical significance of high-frequency
      oscillations (HFOs) on scalp electroencephalography (EEG) in patients with
      epileptic encephalopathy with continuous spike-and-wave during sleep (CSWS).
      METHODS: Twenty-one CSWS patients treated for epilepsy from January 2006 to
      December 2016 in Pediatric Department of Peking University First Hospital were
      enrolled into the study. Selected clinical variables including gender, age
      parameters, seizure frequencies and antiepileptic drugs were compared between
      (a). HFO-positive group and HFO-negative group before methylprednisolone
      treatment and (b). excellent seizure outcome group and not-excellent seizure
      outcome group after methylprednisolone treatment. Interictal HFOs and spikes in
      pre- and post-methylprednisolone scalp EEG were measured and analyzed. RESULTS:
      Before methylprednisolone treatment, there were 12 of 21 (57%) CSWS patients had
      HFOs, with a mean value 43.17 per 60 s per patient. The 12 patients with HFOs
      tended to have more frequent epileptic negative
      myoclonus/atonic/myoclonus/atypical absences than those without HFOs in a month
      before methylprednisolone treatment. A total of 518 HFOs and 22 592 spikes were
      found in the pre-methylprednisolone EEG data of 21 patients, and 441 HFOs (86%)
      were associated with spikes. The highest amplitudes of HFOs were significantly
      positively correlated with that of spikes (r=0.279, P<0.001). Rates reduced by
      methylprednisolone treatment were statistically significant for both HFOs
      (P=0.002) and spikes (P=0.006). The percentage of reduction was 91% (473/518) and
      39% (8 905/22 592) for spikes and HFOs, respectively. The percentage of spike and
      HFOs changes was respectively 100% decrease and 47% decrease in the excellent
      seizure outcome group, and they were 79% decrease and 18% increase in the not
      excellent seizure outcome group. CONCLUSION: Prevalence of HFOs might reflect
      some aspect of epileptic activity. HFOs were more sensitive to methylprednisolone
      treatment than spikes and had a good correlation with the prognosis of seizures,
      and HFOs could be applied to assess epilepsy severity and antiepileptic therapy.

PMID- 29643518
TI  - [Application of anoptomagnetic probe Gd-DO3A-EA-FITC in imaging and analyzing the
      brain interstitial space].
AB  - OBJECTIVE: To investigate the application of the optical magnetic bimodal
      molecular probe Gd-DO3A-ethylthiouret-fluorescein isothiocyanate (Gd -DO3A-EA
      FITC) in brain tissue imaging and brain interstitial space (ISS). METHODS: In the
      study, 24 male SD rats were randomly divided into 3 groups, including magnetic
      probe group (n=6), optical probe group (n=6) and optical magnetic bimodal probe
      group (n=12), then the optical magnetic bimodal probe group was divided equally
      into magnetic probe subgroup (n=6) and optical probe subgroup (n=6). Referencing
      the brain stereotaxic atlas, the coronal globus pallidus as center level, the
      probes including gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA),
      fluorescein isothiocyanate (FITC) and Gd-DO3A-EA-FITC of 2 MUL (10 mmol/L) were
      injected into the caudate nucleus respectively, magnetic resonance imaging (MRI)
      was performed in the magnetic probe group and magnetic probe subgroup to image
      the dynamic diffusion and distribution of the probes in the brain ISS, a self
      developed brain ISS image processing system was used to measure the diffusion
      coefficient, clearance, volume fraction and half-time in these two groups. Laser
      scanning confocal microscope (LSCM) was performed in vitro in the optical probe
      group and optical probe subgroup for fluorescence imaging at the time points 2
      hours after the injection of the probe, and the distribution in the oblique
      sagittal slice was compared with the result of the first two groups. RESULTS: For
      the magnetic probe group and magnetic probe subgroup, there were the same imaging
      results between the probes of Gd-DTPA and Gd-DO3A-EA-FITC. The diffusion
      parameters of Gd-DTPA and Gd-DO3A-EA-FITC were as follows: the average diffusion
      coefficients [(3.31+/-0.11)*10-4 mm2/s vs. (3.37+/-0.15)*10-4 mm2/s, t=0.942,
      P=0.360], the clearance [(3.04+/-0.37) mmol/L vs. (2.90+/-0.51) mmol/L, t=0.640,
      P=0.531], the volume fractions (17.18%+/-0.14% vs. 17.31%+/-0.15%, t=1.961,
      P=0.068), the half-time [(86.58+/-3.31) min vs. (84.61+/-2.38) min, t=1.412,
      P=0.177], the diffusion areas [(23.25+/-0.68) mm2 vs. (22.71+/-1.00) mm2,
      t=1.100, P=0.297]. The statistical analysis of each brain was made by t test, and
      the diffusion parameters were not statistically significant. Moreover, for the
      optical probe group and optical probe subgroup, the diffusion area of Gd-DO3A-EA
      FITC [(22.61+/-1.16) mm2] was slightly larger than that of FITC [(22.10+/-1.29)
      mm2], the statistical analysis of each brain was made by t test, and the
      diffusion parameters were not statistically significant (t=0.713, P=0.492).
      CONCLUSION: Gd-DO3A-EA-FITC shows the same imaging results as the traditional GD
      DTPA, and it can be used in measuring brain ISS.

PMID- 29643519
TI  - [Dynamic visual analysis of neutrophils chemotaxis in peritoneal cavity of
      schizophrenic model in mice].
AB  - OBJECTIVE: To compare the differences of neutrophils chemotaxis ability in
      peritoneal cavity between normal rats and schizopherenic rats with cell dynamic
      visualization system. METHODS: In the study,18 healthy Kunming rats were randomly
      divided into 3 groups which were control group (n=6), 0.3 mg/kg MK-801 treatment
      group (n=6), 0.6 mg/kg dizocilpine maleate (MK-801) treatment group(n=6),
      extracted neutrophils separately, and observed the morphology and counted under a
      microscope. Each group of cells was divided into two parts for chemotactic
      experiment, called chemokine agent treatment group and no chemokine agent
      treatment group respectively, indicating control 1, 0.3 mg/kg MK-801 treatment
      1,0.6 mg/kg MK-801 treatment 1 and control 2, 0.3 mg/kg MK-801 treatment 2,0.6
      mg/kg MK-801 treatment 2. The dynamic migration of cells was recorded using the
      NIS-Elements software, and TAXIScan Analyzer 2 software was used to select 30
      cells (n=30) in each group of cells and analyze cells migration trajectory, speed
      and distance, and use pair test and One-Way analysis of variance for statistical
      analysis. RESULTS: The number of neutrophils in control group, 0.3 mg/kg MK-801
      treatment group and 0.6 mg/kg MK-801 treatment group were(1.00+/
      0.03)*104/mL,(0.05+/-0.02)*104/mL,(0.32+/-0.01)*104/mL respectively, the
      differences of results were statistically significant(P<0.05).Under the effect of
      chemotactic agent,the directional migration capability of neutrophils in control
      group 1, 0.3 mg/kg MK-801 treatment group 1 and 0.6 mg/kg MK-801 treatment group
      1 were(0.85+/-0.11) radian,(1.00+/-0.11) radian,(0.96+/-0.10) radian respectively
      (P<0.05); the migration velocities of neutrophils were (0.09+/-0.02)
      MUm/s,(0.12+/-0.01) MUm/s,(0.14+/-0.01) MUm/s respectively (P<0.05);the migration
      distances of neutrophils were (94.26+/-0.02) MUm,(134.61+/-0.01) MUm,(156.19+/
      0.01) MUm respectively(P<0.05). CONCLUSION: Compared with neutrophils in
      peritoneal cavity of control group, the neutrophils in peritoneal cavity of
      schizophrenic rats have stronger chemotactic movement ability.

PMID- 29643520
TI  - [Comparison of gut microbiotal compositional analysis of patients with irritable
      bowel syndrome through different bioinformatics pipelines].
AB  - OBJECTIVE: To assess whether the same biological conclusion, diagnostic or
      curative effects regarding microbial composition of irritable bowel syndrome
      (IBS) patients could be reached through different bioinformatics pipelines, we
      used two common bioinformatics pipelines (Uparse V2.0 and Mothur V1.39.5)to
      analyze the same fecal microbial 16S rRNA high-throughput sequencing data.
      METHODS: The two pipelines were used to analyze the diversity and richness of
      fecal microbial 16S rRNA high-throughput sequencing data of 27 samples, including
      9 healthy controls (HC group), 9 diarrhea IBS patients before (IBS group) and
      after Rifaximin treatment (IBS-treatment, IBSt group). Analyses such as microbial
      diversity, principal co-ordinates analysis (PCoA), nonmetric multidimensional
      scaling (NMDS) and linear discriminant analysis effect size (LEfSe) were used to
      find out the microbial differences among HC group vs. IBS group and IBS group vs.
      IBSt group. RESULTS: (1) Microbial composition comparison of the 27 samples in
      the two pipelines showed significant variations at both family and genera levels
      while no significant variations at phylum level; (2) There was no significant
      difference in the comparison of HC vs. IBS or IBS vs. IBSt (Uparse: HC vs. IBS,
      F=0.98, P=0.445; IBS vs. IBSt, F=0.47,P=0.926; Mothur: HC vs.IBS, F=0.82,
      P=0.646; IBS vs. IBSt, F=0.37, P=0.961). The Shannon index was significantly
      decreased in IBSt; (3) Both workshops distinguished the significantly enriched
      genera between HC and IBS groups. For example, Nitrosomonas and Paraprevotella
      increased while Pseudoalteromonadaceae and Anaerotruncus decreased in HC group
      through Uparse pipeline, nevertheless Roseburia 62 increased while Butyricicoccus
      and Moraxellaceae decreased in HC group through Mothur pipeline.Only Uparse
      pipeline could pick out significant genera between IBS and IBSt, such as
      Pseudobutyricibrio, Clostridiaceae 1 and Clostridiumsensustricto 1. CONCLUSION:
      There were taxonomic and phylogenetic diversity differences between the two
      pipelines, Mothur can get more taxonomic details because the count number of each
      taxonomic level is higher. Both pipelines could distinguish the significantly
      enriched genera between HC and IBS groups, but Uparse was more capable to
      identity the difference between IBS and IBSt groups. To increase the
      reproducibility and reliability and to retain the consistency among similar
      studies, it is very important to consider the impact on different pipelines.

PMID- 29643521
TI  - [Application of support vector machine in predicting in-hospital mortality risk
      of patients with acute kidney injury in ICU].
AB  - OBJECTIVE: To construct an in-hospital mortality prediction model for patients
      with acute kidney injury (AKI) in intensive care unit (ICU) by using support
      vector machine (SVM), and compare it with the simplified acute physiology score
      II (SAPS-II) which is commonly used in the ICU. METHODS: We used Medical
      Information Mart for Intensive Care III (MIMIC-III) database as data source. The
      AKI patients in the MIMIC-III database were selected according to the 2012 Kidney
      Disease: Improving Global Outcomes (KDIGO) definition of AKI. We employed the
      same predictor variable set as used in SAPS-II to construct an SVM model.
      Meanwhile, we also developed a customized SAPS-II model using MIMIC-III database,
      and compared performances between the SVM model and the customized SAPS-II model.
      The performance of each model was evaluated via area under the receiver operation
      characteristic curve (AUROC), root mean squared error (RMSE), sensitivity,
      specificity, Youden's index and accuracy based on 5-fold cross-validation. The
      agreement of the results between the SVM model and the customized SAPS-II model
      was illustrated using Bland-Altman plots. RESULTS: A total number of 19 044
      patients with AKI were included. The observed in-hospital mortality of the AKI
      patients was 13.58% in MIMIC-III. The results based on the 5-fold cross
      validation showed that the average AUROC of the SVM model and the customized SAPS
      II model was 0.86 and 0.81, respectively (The difference between the two models
      was statistically significant with t=13.0, P<0.001). The average RMSE of the SVM
      model and the customized SAPS-II model was 0.29 and 0.31, respectively (The
      difference was statistically significant with t=-9.6, P<0.001). The SVM model
      also outperformed the customized SAPS-II model in terms of sensitivity and
      Youden's index with significant statistical differences (P=0.002 and <0.001,
      respectively).The Bland-Altman plot showed that the SVM model and the customized
      SAPS-II model had similar mortality prediction results when the mortality of a
      patient was certain, but the consistency between the mortality prediction results
      of the two models was poor when the mortality of a patient was with high
      uncertainty. CONCLUSION: Compared with the SAPS-II model, the SVM model has a
      better performance, especially when the mortality of a patient is with high
      uncertainty. The SVM model is more suitable for predicting the mortality of
      patients with AKI in ICU and early intervention in patients with AKI in ICU. The
      SVM model can effectively help ICU clinicians improve the quality of medical
      treatment, which has high clinical value.

PMID- 29643522
TI  - [Three-dimensional architecture of intraosseous vascular anatomy of the hamate: a
      micro-computed tomography study].
AB  - OBJECTIVE: To obtain three-dimensional intraosseous artery of the hamate and to
      provide the vascular anatomy basis of hamate fracture fixation. METHODS: PbO
      (lead monoxide, Sinopharm Chemical Reagent Beijing Co. Ltd) was ground into
      particles less than 40 MUm and suspended in turpentine oil (Chemical Reagent
      Beijing Co. Ltd) at ratios of 1 g : 1.5 mL, 1 g : 1 mL and 1 g : 0.5 mL. Three
      specimens were investigated. Brachial arteries were cannulated and perfused with
      lead-based contrast agent. Hamates were harvested and scanned using micro
      computed tomography (microCT). The acquisition protocols were as follows: CT scan
      setup: total rotation [Degrees], 360; rotation steps, 360; X-ray detector setup:
      transaxial, 2048; axial, 2048; exposure time, 1 500 ms, Binning, 1; system
      magnification: high-med. X-ray tube setup: 80 kV, 500 mA current. The down
      sampling factor used in the reconstruction was 2. The effective voxel size of the
      final image was 27.30 MUm. The three-dimensional model of the hamate was
      generated and the distribution and pattern of vessels were evaluated. RESULTS:
      There were abundant extraosseous vessels around the hamate. They were mainly
      running in the tendons and ligaments around the hamate. Four vascular zones were
      identified on the hamate surface. They were on the palmar platform of the hamate
      body, on the dorsal side, on the ulnar side and on the tip of hamulus, namely.
      There were anastomoses among 4 vascular zones. We did not observe any vessels
      penetrating through the articular cartilage. The extraosseous vessels of the
      vascular zones gave a number of intraosseous branches into the hamate. The hamate
      body received intraosseous blood supply from the dorsal, palmar and ulnar while
      the hamulus from the palmar, ulnar and hamulus tip. There were some intraosseous
      branches anastomosing with each other. CONCLUSION: The extraosseous and
      intraosseous vessels of the hamate were more than what used to be considered. The
      hamate body and hamulus received blood supply from multiple directions and
      arteries anastomosed extensively both outside and inside the hamate, making it
      possible that the intraosseous perfusion survived after fracture. It is likely
      that the nonunion after the hamate fracture is not caused by the vascular damage
      but the malalignment of the fragments.

PMID- 29643523
TI  - [Mesoporous nano-bioactive glass microspheres as a drug delivery system of
      minocycline].
AB  - OBJECTIVE: To construct mesoporous nano-bioactive glass (MNBG) microspheres load
      release minocycline as an antibacterial drug delivery system. METHODS: Sol-gel
      method was used to synthesze MNBG microspheres as drug carrier. The MNBG
      consisted of SiO2, CaO, and P2O5. According to the content of silicon, MNBG
      microspheres were divided into four groups (60S, 70S, 80S and 90S). Scanning
      electron microscopy (SEM) was used to observe the surface characteristic and
      particle size of MNBG; Nitrogen adsorption-desorption experiment was performed to
      calculate the MNBG's specific surface area and the pore sizes; The Fourier
      transform infrared spectrum (FT-IR) and the thermogravimetric analysis were
      conducted to calculate the loading efficiencies of minocycline hydrochloride; UV
      spectrophotometric was used to determine the cumulative release of minocycline
      from drug-loaded particles in PBS solution within 21 d. Agar diffusion test (ADT)
      was performed to evaluate the antibacterial properties on Enterococcus faecalis.
      The inhibition zone was observed and the diameter was measured. RESULTS: The MNBG
      microspheres had good dispersion, large surface area, and even particle size. The
      pore sizes ranged from 4.77 nm to 7.33 nm. The loading experiment results showed
      that the minocycline hydrochloride loading efficiency of MNBG was related to the
      pore size of the microspheres. Among 60S, 70S, 80S and 90S, 60S MNBG had the
      highest loading efficiency of 16.33% due to its high calcium content and large
      pore sizes. A slow minocycline release rate from MNBG particles in PBS solution
      until d 21 was observed. It was showed that a burst release of 28% of the total
      drug for the first 24 h. A cumulative release of 35% was found, and the final
      concentration of minocycline maintained at about 47 mg/L. ADT showed that mino
      MNBG had inhibitory effect on the growth of Enterococcus faecalis. 1 g/L
      minocycline, 1 g/L mino-MNBG, and 0.1 g/L minocycline presented inhibition zone,
      however, PBS and 1 g/L MNBG didn't. The diameter of the inhibition zone of
      minocycline groups was significant larger than that of mino-MNBG group (P<0.05),
      which was also significant larger than those of PBS and MNBG groups (P<0.05). It
      showed that mino-MNBG drug delivery system had antibacterial properties on
      Enterococcus faecalis. CONCLUSION: The 60S MNBG that can effectively load and
      release minocycline may be an ideal drug carrier.

PMID- 29643524
TI  - [A customized method for information extraction from unstructured text data in
      the electronic medical records].
AB  - OBJECTIVE: There is a huge amount of diagnostic or treatment information in
      electronic medical record (EMR), which is a concrete manifestation of clinicians
      actual diagnosis and treatment details. Plenty of episodes in EMRs, such as
      complaints, present illness, past history, differential diagnosis, diagnostic
      imaging, surgical records, reflecting details of diagnosis and treatment in
      clinical process, adopt Chinese description of natural language. How to extract
      effective information from these Chinese narrative text data, and organize it
      into a form of tabular for analysis of medical research, for the practical
      utilization of clinical data in the real world, is a difficult problem in Chinese
      medical data processing. METHODS: Based on the EMRs narrative text data in a
      tertiary hospital in China, a customized information extracting rules learning,
      and rule based information extraction methods is proposed. The overall method
      consists of three steps, which includes: (1) Step 1, a random sample of 600
      copies (including the history of present illness, past history, personal history,
      family history, etc.) of the electronic medical record data, was extracted as raw
      corpora. With our developed Chinese clinical narrative text annotation platform,
      the trained clinician and nurses marked the tokens and phrases in the corpora
      which would be extracted (with a history of diabetes as an example). (2) Step 2,
      based on the annotated corpora clinical text data, some extraction templates were
      summarized and induced firstly. Then these templates were rewritten using regular
      expressions of Perl programming language, as extraction rules. Using these
      extraction rules as basic knowledge base, we developed extraction packages in
      Perl, for extracting data from the EMRs text data. In the end, the extracted data
      items were organized in tabular data format, for later usage in clinical research
      or hospital surveillance purposes. (3) As the final step of the method, the
      evaluation and validation of the proposed methods were implemented in the
      National Clinical Service Data Integration Platform, and we checked the
      extraction results using artificial verification and automated verification
      combined, proved the effectiveness of the method. RESULTS: For all the patients
      with diabetes as diagnosed disease in the Department of Endocrine in the
      hospital, the medical history episode of these patients showed that, altogether 1
      436 patients were dismissed in 2015, and a history of diabetes medical records
      extraction results showed that the recall rate was 87.6%, the accuracy rate was
      99.5%, and F-Score was 0.93. For all the 10% patients (totally 1 223 patients)
      with diabetes by the dismissed dates of August 2017 in the same department, the
      extracted diabetes history extraction results showed that the recall rate was
      89.2%, the accuracy rate was 99.2%, F-Score was 0.94. CONCLUSION: This study
      mainly adopts the combination of natural language processing and rule-based
      information extraction, and designs and implements an algorithm for extracting
      customized information from unstructured Chinese electronic medical record text
      data. It has better results than existing work.

PMID- 29643525
TI  - [Association between chronic periodontitis and carotid intima-media thickness of
      middle-aged and older adults in Shijingshan community of Beijing].
AB  - OBJECTIVE: To investigate the relationship between periodontal disease and
      subclinical atherosclerosis in middle-aged and older adults in Shijingshan
      community of Beijing. METHODS: In 2005-2010, a total of 830 middle-aged and older
      adults were recruited from Shijingshan community of Beijing, who were divided
      into two groups by severity of periodontitis. A questionnaire, periodontal
      examination, blood biochemical examination, carotid intima-media thickness
      (CIMT), including common carotid artery (CCA-IMT), internal carotid artery (ICA
      IMT) and carotid bifurcation (CB-IMT), were measured of each subject. The
      associations of periodontitis with CIMT was evaluated by multivariable Logistic
      regression analysis and analysis of covariance, adjusted for age, gender,
      education level, hypertension, hyperlipidemia, obesity, smoking, drinking, and
      diabetes. And then anther definition of periodontitis (mild periodontitis:
      percentage of AL>=3 mm <10%; moderate periodontitis: percentage of AL>=3 mm 10%
      30%; severe periodontitis: percentage of AL>=3 mm >=30%) was used to investigate
      the hypotheses that different classification of periodontitis would affect
      results. RESULTS: The subjects with moderate-severe periodontitis were
      characterized by significantly higher levels of CCA-IMT, ICA-IMT, CB-IMT and mean
      CIMT than the mild group. In the univariate analysis, moderate-severe
      periodontitis was associated with an increased risk of ICA-IMT>0.9 mm (adjusted
      OR=1.230, 95% CI: 1.058-1.452, P=0.031). Furthermore, moderate periodontitis was
      associated with an increased risk of CB-IMT>0.9 mm (adjusted OR: 1.297, 95%CI:
      1.117-1.753, P=0.011) and severe periodontitis was associated with an increased
      risk of CB-IMT>0.9 mm (adjusted OR=1.771, 95%CI: 1.176-3.503, P=0.042) according
      to another classification of periodontitis. CONCLUSION: Our data provided
      evidence that periodontitis was associated with CIMT among middle-aged and older
      adults in Shijingshan community of Beijing and different periodontitis
      classification would affect the results.

PMID- 29643526
TI  - [Exploring a new method for superimposition of pre-treatment and post-treatment
      mandibular digital dental casts in adults].
AB  - OBJECTIVE: To explore a cone beam computed tomography (CBCT)-independent method
      for mandibular digital dental cast superimposition to evaluate three-dimensional
      (3D) mandibular tooth movement after orthodontic treatment in adults, and to
      evaluate the accuracy of this method. METHODS: Fifteen post-extraction
      orthodontic treatment adults from the Department of Orthodontics, Peking
      University School and Hospital of Stomatology were included. All the patients had
      four first premolars extracted, and were treated with straight wire appliance.
      The pre- and post-treatment plaster dental casts and craniofacial CBCT scans were
      obtained. The plaster dental casts were transferred to digital dental casts by 3D
      laser scanning, and lateral cephalograms were created from the craniofacial CBCT
      scans by orthogonal projection. The lateral cephalogram-based mandibular digital
      dental cast superimposition was achieved by sequential maxillary dental cast
      superimposition registered on the palatal stable region, occlusal transfer, and
      adjustment of mandibular rotation and translation obtained from lateral
      cephalogram superimposition. The accuracy of the lateral cephalogram-based
      mandibular digital dental cast superimposition method was evaluated with the CBCT
      based mandibular digital dental cast superimposition method as the standard
      reference. After mandibular digital dental cast superimposition using both
      methods, 3D coordinate system was established, and 3D displacements of the lower
      bilateral first molars, canines and central incisors were measured. Differences
      between the two superimposition methods in tooth displacement measurements were
      assessed using the paired t-test with the level of statistical significance set
      at P<0.05. RESULTS: No significant differences were found between the lateral
      cephalogram-based and CBCT-based mandibular digital dental cast superimposition
      methods in 3D displacements of the lower first molars, and sagittal and vertical
      displacements of the canines and central incisors; transverse displacements of
      the canines and central incisors differed by (0.3+/-0.5) mm with statistical
      significance. CONCLUSION: The lateral cephalogram-based mandibular digital dental
      cast superimposition method has the similar accuracy as the CBCT-based mandibular
      digital dental cast superimposition method in 3D evaluation of mandibular
      orthodontic tooth displacement, except for minor differences for the transverse
      displacements of anterior teeth. This method is applicable to adult patients with
      conventional orthodontic treatment records, especially the previous precious
      orthodontic data in the absence of CBCT scans.

PMID- 29643527
TI  - [Association between ADAMTS14 gene polymorphism and the temporomandibular joint
      osteoarthritis in Chinese Han females].
AB  - OBJECTIVE: To investigate the association between single nucleotide polymorphisms
      (SNP) of ADAMTS14 gene rs4747096 and osteoarthritis of the temporomandibular
      joint in Chinese Han females. METHODS: As a case-control study, a total of 213
      Chinese Han females were involved in the present study, which contained 103
      temporomandibular joint osteoarthritis patients and 110 healthy people who had no
      symptoms or signs of temporomandibular joint osteoarthritis as control.
      Peripheral blood samples were collected from each participant. Genomic DNAs of
      temporomandibular joint osteoarthritis patients and healthy control were
      extracted from peripheral venous blood, which were stored in -80  degrees C
      refrigerator by using DNA extraction kits. The designed primers were used for
      polymerase chain reaction (PCR) amplification of specific DNA fragments. Genotype
      was determined by sequencing the PCR products. The software Chromas 2.22 was used
      to analyze the genotype. The genotype distributions, allele frequencies and
      genetic models between the patients and controls were compared. The age
      distribution was checked by t-test. Genotype and allele frequency were detected
      by Chi-square test. RESULTS: In the present study, there were no significant
      differences between the osteoarthritis patients and healthy controls in terms of
      age. The genotype distribution was in accordance with Hardy-Weinberg equilibrium
      in the two groups. The genotype frequency of the ADAMTS14 (rs4747096) in the
      experimental group was 38.8% (AA), 55.4% (AG), and 5.8% (GG), respectively. The
      genotype frequency in the control group was 40.9% (AA), 43.6% (AG), and 15.5%
      (GG), respectively. The difference of genotype frequency of the ADAMTS14
      (rs4747096) was significant between the experimental group and the control group
      (P=0.047). There was no significant difference in allele frequency between the
      two groups (P=0.415). AA and AG genotypes significantly increased the risk of the
      disease compared with GG in dominant model (OR=1.114, 95% CI: 1.015-1.223,
      P=0.028). CONCLUSION: A significant correlationship was found between the
      ADAMTS14 (rs4747096) SNP and the temporomandibular joint osteoarthritis in
      Chinese Han females. The distribution of rs4747096 may be different between
      temporomandibular joint osteoarthritis and healthy population.

PMID- 29643528
TI  - [Comparison of the properties of CD146 positive and CD146 negative subpopulations
      of stem cells from human exfoliated deciduous teeth].
AB  - OBJECTIVE: Stem cells from human exfoliated teeth (SHED) were sorted by
      magnetically activated cell sorting (MACS) technique to obtain the CD146 positive
      and negative cell subpopulation. Then the biological characteristics of these
      subpopulations were compared to explore their specific application potential in
      tissue engineering. METHODS: In this study, freshly extracted deciduous teeth
      without any caries or dental pulp disease were obtained. SHED was isolated using
      enzyme digestion method and then sorted by MACS, CD146 positive cells and CD146
      negative cells were obtained after cell sorting. The biological characteristics
      of the unsorted mixed cells, CD146 positive subpopulation and CD146 negative
      subpopulation were compared. The proliferation ability was detected through cell
      counting kit-8 (CCK-8) and colony-forming unit (CFU). After osteogenic induction,
      alizarin red staining was performed and the gene expression of osteogenic related
      markers was detected by quantitative real-time polymerase chain reaction(qPCR).
      After adipogenic induction, oil-red O staining was performed and the gene
      expression of adipogenic related markers was detected. After neurogenic
      differentiation induction, the expression of neural markers was detected by
      immunofluorescence and the gene expression of neural markers was detected by
      qPCR. RESULTS: SHED of the fifth passage was sorted by MACS. And the CD146
      positive cell subpopulation and CD146 negative cell subpopulation were obtained.
      CCK8 assay showed that the proliferative tendency of the three cell groups was
      consistent, but the proliferation potential of CD146 positive and negative cell
      subpopulations was significantly lower than that of the unsorted cells. The
      colony forming rates of the unsorted mixed cell group, CD146 positive and
      negative populations were 28.6%+/-3%,17.1%+/-2.3% and 27.5%+/-2.5%, respectively.
      After 21 days of osteogenic induction, alizarin red staining and qPCR showed that
      the CD146 positive cell population had more mineralized nodule formation and
      expressed higher level of osteogenic related genes compared with the other two
      groups. After 21 days of adipogenic induction, oil red O staining and qPCR
      results showed that the CD146 negative subpopulation produced more lipid droplets
      and the expression of lipid related genes increased more significantly. After 14
      days of neural induction, cell immunofluorescence and qPCR results showed that
      the unsorted mixed cell group and CD146 positive subpopulation expressed glial
      cell marker, and the expressions of neural precursor cells and neuronal marker
      increased significantly in negative subpopulation. CONCLUSION: The unsorted mixed
      cells showed better proliferative potential than CD146 positive and negative
      subpopulations. The CD146 positive subpopulation was most potent in osteogenic
      differentiation; it was more suitable for bone tissue engineering. The CD146
      negative cells had stronger adipogenic differentiation potential than the other
      two cell groups; different subpopulations differed in neural differentiation.

PMID- 29643529
TI  - [Retrospective study of dental treatment under general anesthesia of 62 disabled
      children and adolescents].
AB  - OBJECTIVE: To retrospectively figure out the oral health status, treatment and
      follow-ups after dental treatment under general anesthesia (DGA) of disabled
      children or adolescents. METHODS: Clinical data of disabled children or
      adolescents and normal children as control received DGA in the Department of
      Pediatric Dentistry, Peking University School and Hospital of Stomatology from
      August 2008 to September 2015 were recorded, including: gender, birth date,
      treatment date, disability type, oral health status before treatment, treatment
      content and follow-ups (in 1 year). Differences among ages and disabilities were
      analyzed statistically. RESULTS: Sixty-two disabled patients and fifty-seven
      controls were recruited, mean aged (9.38+/-5.22) years and (3.00+/-1.41) years.
      Most patients had 10 to 15 problem teeth with which the mean number of the
      disabled children and adolescents was (11.79+/-4.98) while that of the normal
      controls was (12.40+/-4.11). Caries, pulpitis, periapical periodontitis, dental
      trauma and developmental tooth anomalies of the disabled patients accounted for
      67.56%, 13.54%, 15.15%, 1.07%, and 2.68%, respectively and the DMFT/dmft index
      was 11.55+/-5.56 while in the control group those were at
      65.35%,19.09%,14.14%,0,1.41% and 12.23+/-4.42. The DMFT/dmft index of the
      disabled patients in the group 6-12 years (8.35+/-4.69) was significantly less
      than that of the other three groups (P<0.01) while no differences were found in
      disabilities (P=0.239). Resin restoration, pit and fissure sealant, preventive
      resin restoration, pulpotomy, pulpectomy/RCT, extraction and crown of the
      disabled patients were performed as 52.71%, 7.24%, 8.56%, 0.72%, 17.13%, 10.01%
      and 3.62% respectively whereas those made up as 56.31%, 1.27%, 0.13%, 2.29%,
      19.87%, 7.90% and 12.23% in the control group. Thirty-five (56.45%) disabled
      patients and forty-three (75.44%) controls recalled. Problem teeth within one
      year after operation in diabled patients and controls were both nearly twice as
      much as the number within half a year. Restoration loss/fractured mainly occurred
      in anterior primary teeth while secondary/ recurrent caries and
      pulpitis/perapical periodontitis mostly occurred in primary molars. CONCLUSION:
      Oral health status in our disabled children and adolescents is poor. Though
      dental treatment under GA is an effective way to improve the oral health of
      disabled children and adolescents, periodic follow-ups and family oral health
      care are equal important for oral health maintenance.

PMID- 29643530
TI  - [Clinical study of locking-taper implants in patients treated for periodontitis].
AB  - OBJECTIVE: To evaluate the survival rate and peri-implant clinical parameters of
      Locking-Taper implants in patients having lost their teeth due to non
      periodontitis (NP) reasons, chronic periodontitis (CP) and aggressive
      periodontitis (AgP). METHODS: In the study, 145 subjects were installed with 315
      Bicon Locking-Taper implants and followed up for 1-5 years. The subjects and
      implants were classified into three groups, tooth loss by NP, CP and AgP. NP
      included 44 subjects with 100 implants, CP 70 subjects with 132 implants and AgP
      31 subjects with 83 implants. Periodontal parameters before subgingival scaling
      and root planning (T0), at the end of active periodontal therapy (T1) and at the
      time of last recall (T2) were recorded. Right after the installation of final
      restoration and at the time of last recall (T2), peri-implant probing parameters
      were recorded. RESULTS: After active periodontal therapy, mean probing depth (PD)
      in CP and AgP were reduced from 4.05 mm, 5.20 mm at T0 to 3.07 mm, 2.96 mm at T1
      (P<0.001, P<0.001), (PD>=6 mm)% were reduced from 33.2%, 58.5% at T0 to 14.4%,
      10.5% at T1 (P<0.001, P<0.001). The periodontal parameters remained stable at T2
      compared with T1 (P>0.05). Cumulative survival rates of implants in NP, CP and
      AgP were 100%, 97.6% and 100% for 1-5 years' follow-ups with no statistical
      significance found. At T2, mean implant PD was 2.78 mm, 2.96 mm and 2.97 mm in
      NP, CP and AgP, with NP significantly lower than the other two groups (P=0.006,
      P=0.01). The percentage of implant sites with PD>=6 mm was 3.7% in CP and 4.8% in
      AgP, both significantly higher than NP (P=0.003, P<0.001). 8.4% implant sites
      showed at least 2 mm deeper than those at prosthesis installation were found in
      CP group, significantly higher than NP (4.3%, P=0.003). CONCLUSION: Periodontal
      conditions of patients having lost their teeth for chronic and aggressive
      periodontitis were significantly improved after active periodontal therapy and
      remained stable during 1-5 years. Short-term survival rates of Locking-Taper
      implants in patients treated for CP and AgP was no less than those who lost their
      teeth for non-periodontitis reasons. More sites with increasing peri-implant
      probing depth were found in CP and AgP patients, compared with NP.

PMID- 29643531
TI  - [Extraction-orthodontic treatment on patients with chronicperiodontitis: a
      preliminary study].
AB  - OBJECTIVE: To retrospectively evaluate clinical and radiographic records of
      chronic periodontitis patients who underwent extraction-orthodontic treatment, in
      order to determine the effect of the treatment on probing depth, alveolar bone
      height of teeth adjacent to the extraction sites. METHODS: In the study, 33
      chronic periodontitis patients who had finished extraction-orthodontic treatment
      were selected, the periodontal examination system tables and panoramic tomography
      were recorded before treatment (T0) and after treatment (T1), and the periodontal
      probing depth (PD), residual alveolar bone height (RBH) of the teeth adjacent to
      extraction sites (TAES) and the non-teeth adjacent to extraction sites (NTAES)
      were measured at T0 and T1. RESULTS: There was insignificant difference in PD of
      TAES and NTAES at T0 [(2.40+/-0.51) mm vs. (2.42+/-0.55) mm,P>0.05], neither was
      that at T1 [(2.70+/-0.67) mm vs. (2.67+/-0.64) mm, P>0.05]; From T0 to T1, PD of
      TAES and NTAES had mean increases of 0.3 mm [(2.40+/-0.51) mm vs. (2.70+/-0.67)
      mm,P<0.01] and 0.25 mm [(2.42+/-0.55 mm vs. (2.67+/-0.64) mm, P<0.01],
      respectively. And PD of TAES and NTAES increased from T0 to T1 statistically in
      the same degree [(0.30+/-0.64) mm vs. (0.25+/-0.58) mm,P>0.05]; at T0, RBH of
      TAES was 0.024 smaller than that of NTAES (0.74+/-0.16 vs. 0.76+/-0.16,P<0.05),
      but there was no difference in RBH between the TAES and NTAES at T1 (0.78+/-0.14
      vs. 0.79+/-0.12,P>0.05); From T0 to T1, RBH of TAES and NTAES had mean increases
      of 0.04 (0.74+/-0.16 vs.0.78+/-0.14,P<0.05) and 0.02 (0.76+/-0.16 vs. 0.79+/
      0.12,P<0.05), respectively. And the change of RBH between TAES and NTAES from T0
      to T1 had no statistical difference (0.04+/-0.11 vs. 0.02+/-0.08,P>0.05)RBH of
      TAES in the side close to extraction sites was as the same as that of TAES in the
      side away from the extraction sites at T0 (0.73+/-0.17 vs. 0.74+/-0.16,P>0.05).
      From T0 to T1, RBH of both sides of TAES had mean increases of 0.04 (0.73+/-0.11
      vs. 0.77+/-0.11,P<0.05) and 0.04 (0.74+/-0.11 vs. 0.78+/-0.11,P<0.05),
      respectively. But for both sides of TAES, from T0 to T1, there was no significant
      difference in change of RBH (0.04+/-0.11 vs. 0.04+/-0.11,P>0.05). CONCLUSIONS:
      With strict control of periodontal inflammation and maintenance of oral hygiene,
      orthodontic treatment preserves the periodontal conditions in patients with
      chronic periodontitis, and the extraction-orthodontic treatment can preserve the
      bone height of the teeth adjacent to extraction sites.

PMID- 29643532
TI  - [Three-year clinical effects of a modified semi-fixed bridge on restoring a
      missing posterior tooth].
AB  - OBJECTIVE: To observe the effects of a modified semi-fixed bridge to restore a
      missing posterior tooth for three years. METHODS: In the study, 38 cases with a
      posterior tooth missed were chosen as experiment group. The inclusion criteria
      for these cases required that one abutment tooth be defected, and another
      abutment intact. The missed posterior tooth was restored with a modified semi
      fixed bridge in which a metal wing retainer was applied to the intact abutment
      tooth and a full crown retainer was applied to the defected abutment tooth, and
      the non-rigid connector linked to the metal wing retainer and the pontic, while
      the rigid connector linked to the full crown retainer and the pontic. And 42
      cases with same abutment conditions were chosen as control group. These control
      patients were treated with classical rigidly-fixed partial dentures. The clinical
      effects regarding the bridge survival, abutment conditions, and etc. were
      observed by examination. RESULTS: The average observation time for experiment
      group was 40.3 months (from 9 to 60 months). One case failed with loose crown
      retainer after 7 months' usage. Another failed case was the same performance
      after 20 months' wearing. The restorations were rebounded after the inner face of
      crowns was treated, and they were used normally. No loose abutment and retainer,
      no decayed abutment teeth were found, and the marginal adaptations between
      retainers and abutment teeth were good. The average observation time of control
      group was 44.7 months(from 22 to 50 months). No secondary decays and loose
      abutment teeth were detected and the marginal adaptation of the retainers was
      good. CONCLUSION: This modified semi-fixed bridge has similar survival rate and
      clinical effects to restore a missing posterior tooth when compared with the
      traditional rigidly-fixed partial dentures. But the long-term observation is
      required.

PMID- 29643533
TI  - [Topoisomerase inhibitor upregulates MICA/B expression in breast cancer cells
      through ATM/ATR and NF-kappaB pathway].
AB  - OBJECTIVE: To investigate the effects of chemotherapeutic agents widely used in
      clinical practice on major histocompatibility complex class I-related chain A and
      B (MICA/B) expression in breast cancer cells, and to explore the molecular
      mechanisms involved. METHODS: We examined MICA/B mRNA and surface protein
      expressions in breast cancer cells treated with chemotherapeutic agents by real
      time RT-PCR and flow cytometry respectively. The blocking effects of ataxia
      telangiectasia mutated and Rad3-related kinase (ATM/ATR) inhibitor caffeine and
      nuclear factor kappaB (NF-kappaB) inhibitor pynolidine dithiocarbamate (PDTC) on
      etoposide-upregulated MICA/B mRNA and surface protein expressions were
      investigated. Electrophoretic mobility shift assay (EMSA) was taken to
      investigate whether etoposide enhanced the binding of NF-kappaB to MICA/B gene
      promoter. RESULTS: Three topoisomerase inhibitors etoposide, camptothecin and
      doxorubicine upregulated MICA and MICB mRNA expressions in breast cancer cell MCF
      7. Comparing to no-drug-treated cells, MICA mRNA levels increased to (1.68+/
      0.17), (2.54+/-0.25) and (3.42+/-0.15) fold, and levels of MICB mRNA increased to
      (1.82+/-0.24), (1.56+/-0.05) and (5.84+/-0.57) fold respectively in cancer cells
      treated by etoposide at the concentrations of 5, 20 and 100 MUmol/L (P<0.05).
      MICA and MICB mRNA levels also increased significantly when MCF-7 cells were
      incubated with camptothecin or doxorubicine at the specific concentrations
      (P<0.05). MICB mRNA expression also increased slightly in another breast cancer
      cell SK-BR-3 treated by topoisomerase II inhibitors etoposide and camptothecin
      (P<0.05). Furthermore, etoposide and camptothecin upregulated MICA/B surface
      protein expression in MCF-7 cells (P<0.05), and the upregulation was found in
      both living and apoptotic cells. Our study showed that etoposide induced-MICA/B
      expression in MCF-7 was inhibited by caffeine at different concentrations. When
      cancer cells were treated by caffeine with 1, 5 and 10 mmol/L, MICA mRNA levels
      decreased from (3.75+/-0.25) to (0.89+/-0.05), (0.81+/-0.02) and (0.48+/-0.04)
      fold respectively (P<0.001), and MICB mRNA levels decreased from (6.85+/-0.35) to
      (1.36+/-0.13), (0.76+/-0.06) and (0.56+/-0.03) fold (P<0.05), while MICA/B
      protein levels decreased from (3.42+/-0.05) to (1.32+/-0.03), (1.21+/-0.06) and
      (1.14+/-0.03) fold (P<0.001), indicating that etoposide-induced MICA/B expression
      was inhibited by ATM/ATR inhibitor. Similarly, NF-kappaB inhibitor PDTC also
      inhibited MICA/B mRNA and protein expressions induced by etoposide significantly
      when MCF-7 cells were incubated with PDTC at the concentrations of 10, 50 and 100
      MUmol/L (P<0.05), indicating that NF-kappaB was also involved in this process.
      EMSA showed that the binding of NF-kappaB to MICA/B promoter enhanced in MCF-7
      cells after etoposide treatment. CONCLUSION: Topoisomerase inhibitor increased
      MICA/B mRNA and protein expressions in breast cancer cells, indicating that
      chemotherapeutic agents might increase the recognizing and killing ability of
      immunocytes to breast cancer cells. ATM/ATR and NF-kappaB pathways might be
      involved in it.

PMID- 29643534
TI  - [In vivo imaging of breast tumors by a 99mTc radiolabeled probe targeting
      microRNA-155 in mice models].
AB  - OBJECTIVE: MicroRNA-155 (miR-155) is significantly highly expressed in breast
      cancer, lung cancer, liver cancer and other malignant tumors. This study was to
      design and construct a radiolabeled probe targeting miR-155 for in vivo imaging
      in breast cancer. METHODS: Anti-miR-155 oligonucleotide (AMO-155) was chemically
      synthesized with 2' OMe modification. Its 5' end was linked with acetyl amine
      group. After chelated with a bifunctional chelator NHS-MAG3, AMO-155 was
      radiolabeled with 99mTc using stannous chloride. The serum stability was
      evaluated at cellular level. In vivo imaging was performed in MCF-7 tumor bearing
      mice after the administration of 99mTc radiolabeled AMO-155 and scramble control
      probes, respectively. Furthermore, the blocked imaging of tumor bearing mice was
      obtained after the injection of unlabeled AMO-155 2 hours ahead. MCF-7 and MDA-MB
      231 tumor bearing mice with different expression level of miR-155 were imaged,
      respectively. Quantitative real-time PCR (qRT-PCR) was used to identify the
      expression level of miR-155 in the bearing tumors. RESULTS: 99mTc-AMO-155 was
      prepared with high radiolabeled efficiency (97%), radiochemical purity (greater
      than 98%), and radioactive specific activity (3.75 GBq/MUg). 99mTc-AMO-155 was
      stable in fresh human serum for 12 hours. After the administration via tail vein,
      99mTc-AMO-155 displayed significant accumulation in MCF-7 bearing tumors with
      high expression level of miR-155, whereas 99mTc-control showed little
      accumulation. After blocked with unlabeled AMO-155, the tumor could not be
      visualized clearly after the administration of 99mTc-AMO-155. Furthermore, 99mTc
      AMO-155 could show the differential expression of miR-155 in vivo. MCF-7 tumor
      was shown with significantly higher radioactive accumulation than MDA-MB-231,
      based on its higher expression level of miR-155, which was verified by qRT-PCR.
      CONCLUSION: 99mTc-labeled AMO-155 with chemical modification showed good serum
      stability and in vivo tumor targeting ability. This study provides a potential
      probe for in vivo imaging of breast cancer.

PMID- 29643535
TI  - [Effects of tetrandrine on proliferation and activation of cardiac fibroblasts].
AB  - OBJECTIVE: To investigate the effects of tetrandrine (Tet) on proliferation and
      activation of rat cardiac fibroblasts. METHODS: Firstly, the cell counting kit-8
      (cck-8) assay was applied to detect the effects of Tet with different
      concentrations on proliferation of cardiac fibroblasts. Secondly, transforming
      growth factor (TGF-beta)with a concentration of 5 MUg/L was used to induce the
      cardiac fibroblast activation, and Western blot was performed to measure the
      expression variation of beta-catenin, vimentin (Vm), fibronectin (Fn) and smooth
      muscle alpha-actin (SMA). At last, the real-time PCR was conducted to measure the
      expression change of collagen-1(Col-1) and collagen-3(Col-3). RESULTS: The cck-8
      assay showed that the Tet with different concentrations respectively, which were
      0.5 MUmol/L, 1 MUmol/L, 2 MUmol/L, 4 MUmol/L, and 8 MUmol/L, significantly
      inhibited the proliferation of cardiac fibroblasts. The viability was decreased
      to 94.4%,84.9%,74.9%,63.8%and 50.3% respectively of the control group when the
      Tet concentration changed, and the difference was statistically significant,
      P=0.043, P<0.001, P<0.001, P<0.001, P<0.001 respectively. Western blot revealed
      that the expressions of beta-catenin, Fn, SMA and Vm, were up-regulated by TGF
      beta(5 MUg/L), the result showed that the difference was statistically
      significant, and the P values were 0.001,0.008,0.010,0.001 respectively. Then,
      the up-regulation of beta-catenin, Fn and SMA was attenuated by pre-treatment of
      Tet, and the result also displayed that the difference was statistically
      significant, and the P values were 0.009, 0.005, 0.019,respectively. While there
      was no significant change in the expression of Vm, according to Western blotting,
      and P>0.05,at the same time, real-time PCR indicated that the up-regulations of
      Col-1 and Col-3 which were induced by TGF-beta were blocked by pre-treatment of
      Tet, the result showed that the difference was statistically significant,
      P<0.001. CONCLUSION: According to the experimental results, we can draw the
      conclusion that: the Tet can significantly inhibit the proliferation of cardiac
      fibroblasts, meanwhile, it can block the activation of cardiac fibroblasts, which
      is induced by TGF-beta. It is supposed that the Tet may probably have anti
      myocardial fibrosis, which indicates that it may probably be a medicine which is
      used to block the cardiac remodeling.

PMID- 29643536
TI  - [Genetic diagnosis of Caroli syndrome with autosomal recessive polycystic kidney
      disease: a case report and literature review].
AB  - This case report is about one genetically specified diagnosed infant case of
      Caroli syndrome with autosomal recessive polycystic kidney disease (ARPKD) in
      China. The patient in this case report was an eight-month infant boy with an
      atypical onset and the main clinical manifestation was non-symptomatic
      enlargement of the liver and kidneys. The imaging study demonstrated a diffused
      cystic dilatation of intrahepatic bile ducts as well as polycystic changes in
      bilateral kidneys. The basic blood biochemical tests indicated a normal
      hepatorenal function. Four serum biomarkers of hepatic fibrosis were all elevated
      and the urine test for an early detection of the renal injury was positive. The
      genetic sequencing proved two heterozygous missense mutations of polycystic
      kidney and hepatic disease 1 (PKHD1) gene, c.9292G>A and c.2507T>C, inherited
      from each of his parents respectively. The former was a novel mutation that had
      been verified as disease causing through the predicting software while the latter
      had been reported from one recent case study on Chinese twins, which was possibly
      unique among Chinese population. The relations between the gene type and the
      clinical phenotype were not clarified yet. Up till a follow-up eleven months
      later after the discharge, the patient had a normal hepatorenal function without
      occurrence of any severe complication yet. The clinical symptoms of Caroli
      syndrome with ARPKD at infant stage were atypical and the enlargement of liver
      and kidney was usually the sole symptom. From the above systematic retrospective
      clinical analysis, as well as the relevant literature review, it's been concluded
      that the features of the hepatorenal images in patients with Caroli syndrome and
      ARPKD were distinctive. Genetic testing combined with the imaging study benefits
      a definite diagnosis as well as a differentiation from other hepatorenal
      fibrocystic diseases. Specific to the long-term management of this kind of
      patients, it's necessary to schedule a regular follow-up to monitor the
      hepatorenal function and the occurrence of various complications for an
      appropriate intervention, meantime to devote efforts to the genetic counseling
      work for the patients' family.

PMID- 29643537
TI  - [Preparation and characterization of citric acid-modified superparamagnetic iron
      oxide nanoparticles].
AB  - OBJECTIVE: To prepare and characterize citric acid (CA)-modified super
      paramagnetic iron oxide nanoparticles (SPIONs) for magnetic targeting,
      hyperthermia and magnetic resonance imaging (MRI). METHODS: CA-modified SPIONs
      (CA-SPIONs) were prepared by co-precipitation method and then the magnetic
      responsiveness, morphology, particle size, infrared feature, weight percentage of
      CA, magnetic property and X-ray diffraction pattern of CA-SPIONs were
      respectively characterized by magnet, transmission electron microscope, laser
      particle size analyzer, Fourier transform infrared (FT-IR) spectroscopy,
      thermogravimetry-differential thermal analyzer, vibrating sample magnetometer and
      X-ray diffractometer (XRD). The heating efficiency of the CA-SPIONs was
      investigated by a high frequency induction heater. The transverse relaxivity (r2)
      of the CA-SPIONs was evaluated by a 3.0 T MRI scanner. RESULTS: The CA-SPIONs
      prepared were dispersed well in water with a dark black color and had good
      magnetic responsiveness. The CA-SPIONs were spherical in shape and uniform in
      size with an average size around 12 nm. The hydrodynamic average size of the CA
      SPIONs was (72.35+/-4.47) nm with a polydispersity index of 0.231 +/- 0.029. The
      result of infrared spectrum indicated that CA was successfully modified to the
      surface of SPIONs. The result of thermogravimetric analysis showed that the
      weight percentage of CA modified on the CA-SPIONs was 9.0%. The result of
      magnetic property evaluation demonstrated that the CA-SPIONs exhibited excellent
      superparamagetism with a saturation magnetism of 63.58 emu/g. The XRD result
      indicated that the CA-SPIONs were in inverse spinel structure. The crystallite
      size of the CA-SPIONs was calculated to be 12.4 nm by Debye-Scherrer equation.
      Under the high frequency alternating electromagnetic field with electric current
      of 9 A and frequency ranging from 45 to 50 kHz, the CA-SPIONs exhibited excellent
      heating efficiency and the specific absorption rate (SAR) value was calculated to
      be 26 W/g. The r2 of the CA-SPIONs was assessed to be 338 (mmol/L)-1*s-1 by a 3.0
      T MRI scanner, which suggested the excellent negative contrast enhancement effect
      of the CA-SPIONs. CONCLUSION: The CA-SPIONs are expected to be used as a
      promising agent for magnetic targeting, hyperthermia and MRI detection.

PMID- 29643538
TI  - [Anterior cervical discectomy and fusion to treat cervical spondylosis with
      sympathetic symptoms].
AB  - OBJECTIVE: To investigate the clinical effectiveness of polytheretherketone
      (PEEK) cages assisted anterior cervical discetomy and fusion (ACDF) to treat
      cervical spondylosis with sympathetic symptoms. METHODS: Retrospective analysis
      was undertaken for 39 patients who were diagnosed as cervical spondylosis with
      sympathetic symptoms and underwent ACDF with PEEK cages. Radiographs obtained
      before surgery, after surgery, and at the final follow-up were assessed for
      quality of fusion. The following criteria were used for assessing radiographic
      success of fusion: (1) endplate obliterated with no lucent lines; (2)
      obliteration of disc space by bony trabeculae; (3) less than 2 degrees of
      intervertebral motion or 2 mm of motion between the spinous processes at the
      operated segment on flexion-extension lateral radiographs. The sympathetic
      symptoms including vertigo, headache, tinnitus, nausea and vomiting, heart throb,
      hypomnesia and gastroenterological discomfort were scored by 20-point system
      preoperatively, 2 months postoperatively and at the final follow-up. The recovery
      rate and clinical satisfaction rate were also evaluated. Surgical complications
      were also assessed. RESULTS: They were followed up for at least one year. The
      mean follow-up was 15.6 months. Radiographs of the cervical spine at the last
      follow-up revealed a solid fusion with no signs of a pseudoarthrosis in 36 cases.
      In two patients delayed union and bony fusion were achieved at the end of 9 and
      11 months. Pseudoarthosis was found in 1 case but the patient had no symptoms.
      The score of sympathetic symptoms before surgery, 2 months after surgery and at
      the final follow-up were 8.4+/-1.0,2.2+/-0.3,and 2.4+/-0.3, respectively. There
      were 22 excellent cases, 15 good cases, 1 fair case and 1 bad case in terms of
      RR. Good to excellent results were attained in 95% of theses patients. The
      sympathetic symptoms improved in all the patients and the score was significantly
      improved after surgery. There was one patient who had cerebral spinal fluid
      leakage but he recovered one week after surgery. Two patients felt a mild
      swallowing discomfort, but it disappeared within one month after surgery.
      Subcutaneous hematoma occurred in one patient due to obstructed drainage. It was
      cleared two days after surgery. CONCLUSION: Cervical spondylosis patients with
      sympathetic symptoms may be managed successfully with ACDF using PEEK cages.
      Successful clinical results regarding symptom improvement and general
      satisfaction with the surgical procedure depend not only on obtaining successful
      decompression and radiographic fusion but also on patient selection.

PMID- 29643539
TI  - [Construction of chemical information database based on optical structure
      recognition technique].
AB  - OBJECTIVE: To create a protocol that could be used to construct chemical
      information database from scientific literature quickly and automatically.
      METHODS: Scientific literature, patents and technical reports from different
      chemical disciplines were collected and stored in PDF format as fundamental
      datasets. Chemical structures were transformed from published documents and
      images to machine-readable data by using the name conversion technology and
      optical structure recognition tool CLiDE. In the process of molecular structure
      information extraction, Markush structures were enumerated into well-defined
      monomer molecules by means of QueryTools in molecule editor ChemDraw. Document
      management software EndNote X8 was applied to acquire bibliographical references
      involving title, author, journal and year of publication. Text mining toolkit
      ChemDataExtractor was adopted to retrieve information that could be used to
      populate structured chemical database from figures, tables, and textual
      paragraphs. After this step, detailed manual revision and annotation were
      conducted in order to ensure the accuracy and completeness of the data. In
      addition to the literature data, computing simulation platform Pipeline Pilot 7.5
      was utilized to calculate the physical and chemical properties and predict
      molecular attributes. Furthermore, open database ChEMBL was linked to fetch known
      bioactivities, such as indications and targets. After information extraction and
      data expansion, five separate metadata files were generated, including molecular
      structure data file, molecular information, bibliographical references,
      predictable attributes and known bioactivities. Canonical simplified molecular
      input line entry specification as primary key, metadata files were associated
      through common key nodes including molecular number and PDF number to construct
      an integrated chemical information database. RESULTS: A reasonable construction
      protocol of chemical information database was created successfully. A total of
      174 research articles and 25 reviews published in Marine Drugs from January 2015
      to June 2016 collected as essential data source, and an elementary marine natural
      product database named PKU-MNPD was built in accordance with this protocol, which
      contained 3 262 molecules and 19 821 records. CONCLUSION: This data aggregation
      protocol is of great help for the chemical information database construction in
      accuracy, comprehensiveness and efficiency based on original documents. The
      structured chemical information database can facilitate the access to medical
      intelligence and accelerate the transformation of scientific research
      achievements.

PMID- 29643540
TI  - [Verification of skin paste electrodes used in wireless polysomnography].
AB  - OBJECTIVE: To explore an electrode suitable for wireless portable sleep
      monitoring equipment and analyze the result of the signals of electrooculogram
      (EOG) and electroencephalography (EEG) collected by this kind of flexible
      electrodes. METHODS: The flexible electrodes were prepared by
      microelectromechanical systems (MEMS) technology. This kind of electrodes
      consisted parylene, chromium, and gold. Parylene, the flexible substrate of this
      kind of flexible electrodes, was of biocompatibility. Between parylene and gold
      there was an adhesion layer of chromium, which connected parylene and gold
      tightly. Then the flexible electrodes were stuck to medical adhesive tape. The
      electrodes were designed and made into a grid to make sure that the medical
      adhesive tape could tape on the skin tightly, so that the contact impedance
      between the electrodes and the skin would be reduced. Then the alternating
      current impedance of the electrode were tested by the CHI660E electrochemical
      workstation after the electrode was achieved. To make sure that this kind of
      electrodes could be used in EOG monitoring, the electrodes were connected to a
      wireless signal acquisition suite containing special biological signal
      acquisition and digital processing chip to gather different sites around the eyes
      and the electrical signals of different directions of the eye movements, then
      analyzed the signal-to-noise ratio of the EOG. At the end, the Philips A6
      polysomnography was used to compare the noise amplitude of the EEG signals
      collected by the flexible electrode and the gold cup electrode. RESULTS: The
      electrodes stuck to the skin tightly, and these electrodes could collect signals
      that we wanted while the experiment was performed. The alternating current
      impedance of the flexible electrode was between 4 kOmega and 13 kOmega while with
      the frequency of alternating current under 100 Hz, most EEG signal frequencies
      were at this range. The EOG signals collected by the flexible electrodes were in
      line with the clinical requirements. The noise amplitude of EEG signals collected
      by the flexible electrodes was lower than that of the electrical signals
      collected by the gold cup electrodes. CONCLUSION: The flexible electrode could be
      taken into consideration as an alternative electrode for monitoring EOG and EEG
      signals, and the wireless portable sleep monitoring devices are to be further
      developed in the future.

PMID- 29643541
TI  - [Preparation, quality control and thyroid molecule imaging of solid-target based
      radionuclide ioine-124].
AB  - OBJECTIVE: To provide useful information for the further production and
      application of this novel radio-nuclide for potential clinical application.
      METHODS: 124Te (p,n) 124I nuclide reaction was used for the 124I production.
      Firstly, the target material, 124TeO2 (200 mg) and Al2O3 (30 mg) mixture, were
      compressed into the round platinum based solid target by tablet device. HM-20
      medical cyclotron was applied to irradiate the solid target slice for 6-10 h with
      helium and water cooling. Then, the radiated solid target was placed for 12 h
      (overnight) to decay the radioactive impurity; finally, 124I was be purified by
      dry distillation using 1 mL/min nitrogen for about 6 hours and radiochemical
      separation methods. Micro-PET imaging studies were performed to investigate the
      metabolism properties and thyroid imaging ability of 124I.After 740 kBq 124I was
      injected intravenously into the tail vein of the normal mice, the animals were
      imaged with micro-PET and infused with CT. The micro-PET/CT infusion imaging
      revealed actual state 124I's metabolism in the mice. RESULTS: It was been
      successfully applied for 200 mg 124TeO2 plating by the tablet device on the
      surface of platinum. It showed smooth, dense surface and without obviously pits
      and cracks. The enriched 124Te target was irradiated for 6 to 10 hours at about
      12.0 MeV with 20 MUA current on HM-20 cyclotron. Then 370-1 110 MBq 124I could be
      produced on the solid target after irradiation and 370-740 MBq high specific
      activity could be collected afterdry distillation separation and radio-chemical
      purification.124I product was finally dissolved in 0.01 mol/L NaOH for the future
      distribution. The gamma spectrum of the produced 124I-solution showed that
      radionuclide purity was over 80.0%. The micro-PET imaging of 124I in the normal
      mice exhibited the thyroid and stomach accumulations and kidney metabolism, the
      bladder could also be clearly visible, which was in accordance with what was
      previously reported. To the best of our knowledge, it was the first production of
      124I report in China. CONCLUSION: In this study, the preparation of 124TeO2 solid
      target was successfully carried out by using the tablet device. After irradiation
      of the 124TeO2 solid target and radio-chemical purification, we successfully
      produced 370-740 MBq high specific activity 124I by a cyclotron for biomedical
      application, and micro-PET imaging of 124I in normal mice exhibited the thyroid
      accumulations. Also, slight uptake in stomach were also monitored with almost
      nonuptake in other organs in the micro-PET imaging. The production of 124I is
      expected to provide a new solid target radionuclide for the scientific research
      and potential clinical application of our country.

PMID- 29643542
TI  - [A retrieval method of drug molecules based on graph collapsing].
AB  - OBJECTIVE: To establish a compact and efficient hypergraph representation and a
      graph-similarity-based retrieval method of molecules to achieve effective and
      efficient medicine information retrieval. METHODS: Chemical structural formula
      (CSF) was a primary search target as a unique and precise identifier for each
      compound at the molecular level in the research field of medicine information
      retrieval. To retrieve medicine information effectively and efficiently, a
      complete workflow of the graph-based CSF retrieval system was introduced. This
      system accepted the photos taken from smartphones and the sketches drawn on
      tablet personal computers as CSF inputs, and formalized the CSFs with the
      corresponding graphs. Then this paper proposed a compact and efficient hypergraph
      representation for molecules on the basis of analyzing factors that directly
      affected the efficiency of graph matching. According to the characteristics of
      CSFs, a hierarchical collapsing method combining graph isomorphism and frequent
      subgraph mining was adopted. There was yet a fundamental challenge, subgraph
      overlapping during the collapsing procedure, which hindered the method from
      establishing the correct compact hypergraph of an original CSF graph. Therefore,
      a graph-isomorphism-based algorithm was proposed to select dominant acyclic
      subgraphs on the basis of overlapping analysis. Finally, the spatial similarity
      among graphical CSFs was evaluated by multi-dimensional measures of similarity.
      RESULTS: To evaluate the performance of the proposed method, the proposed system
      was firstly compared with Wikipedia Chemical Structure Explorer (WCSE), the state
      of-the-art system that allowed CSF similarity searching within Wikipedia
      molecules dataset, on retrieval accuracy. The system achieved higher values on
      mean average precision, discounted cumulative gain, rank-biased precision, and
      expected reciprocal rank than WCSE from the top-2 to the top-10 retrieved
      results. Specifically, the system achieved 10%, 1.41, 6.42%, and 1.32% higher
      than WCSE on these metrics for top-10 retrieval results, respectively. Moreover,
      several retrieval cases were presented to intuitively compare with WCSE. The
      results of the above comparative study demonstrated that the proposed method
      outperformed the existing method with regard to accuracy and effectiveness.
      CONCLUSION: This paper proposes a graph-similarity-based retrieval approach for
      medicine information. To obtain satisfactory retrieval results, an isomorphism
      based algorithm is proposed for dominant subgraph selection based on the subgraph
      overlapping analysis, as well as an effective and efficient hypergraph
      representation of molecules. Experiment results demonstrate the effectiveness of
      the proposed approach.

PMID- 29643543
TI  - [Airway foreign body caused by aspiration of artificial nasal sponge: a case
      report].
AB  - 57-year-old male was admitted to hospital for severe headache and seizure attacks
      on November 6th, 2016. After radiology and spinal fluid examination, he was
      diagnosed with viral encephalitis and treated with antiviral medicine,
      antibiotics and mannitol, but he was in sustained unconsciousness and weak in
      expectorating. The patient was given oxygen through artificial nasal after
      bedside tracheotomy. At 1:00 am on January 12th, 2016, there was a sudden drop in
      blood pressure, heart rate and oxygen saturation with left lung breath sounds
      slightly lower than the other side. The patient was connected to a ventilator
      with tidal volume of 300-500 mL and airway pressure of 16-24 cmH2O (1 cmH2O=0.098
      kPa). In the meanwhile, the left side sponge of artificial nasal was found
      missing. Bedside chest X-ray showed no significant atelectasis. At that time the
      evidence of airway foreign body aspiration was not sufficient, so no urgent
      bronchoscopy was performed. At 9:00 am on January 14th, 2016, there was another
      sudden decline in oxygen saturation with diminished left lung breath sounds and
      decreased left thoracic activity. Since left atelectasis could not be ruled out,
      bedside bronchoscopy was performed. In the operation, two sponge-like objects
      were found at the left main bronchus and the opening of left upper lobe
      bronchial. Foreign body forceps were used to remove them. The foreign bodies were
      proved to be the left sponge of artificial nasal afterwards. Symptoms and signs
      caused by aspiration of foreign body in adults were widely various and depending
      on the nature of the foreign body, site, time and whether there was infection or
      not. Foreign body aspiration caused by artificial nasal sponge was rare in
      clinical practice. This case was a living reminder to perform bronchoscopy when
      foreign body aspiration was suspected. For the unconscious and elderly patient,
      whose history of foreign body aspiration usually could not be clearly provided,
      when atelectasis was suspected, bronchoscopy should be performed progressively,
      and more effective measures should be taken to prevent sponge of artificial nasal
      displacement.

PMID- 29643544
TI  - [Bronchial adenoid cystic carcinoma masquerading as bronchial asthma: a case
      report].
AB  - Here we reported a case of bronchial adenoid cystic carcinoma from Peking
      University Third Hospital. A 40-year-old female presented with dry cough for 1
      year and nocturnal paroxysmal attacks of wheezing for 4 months. She was a non
      smoker, and did not have past histories of asthma or allergy. On physical
      examination, no stridor, wheezing and cyanosis were present and the general
      appearance was good. The results of the laboratory analysis, including blood
      eosinophils count, immunoglobulin E level and chest X-ray were normal. Spirometry
      revealed reversible airflow obstruction, and post-bronchodilator forced
      expiratory volume in one second (FEV1) showed an increase of 12% and 230 mL from
      baseline. Bronchial asthma was diagnosed, however, she responded poorly despite
      the adequate anti-asthma therapy including high dose inhaled corticosteroid plus
      long-acting beta2-agonist, theophylline and montelukast. Then chest computed
      tomography (CT) was performed which showed a polypoid mass occupying the lumen of
      left main bronchus. Then the bronchoscopy revealed a polypoid endo-bronchial mass
      arising from the left main bronchus, causing subtotal obstruction of the lumen.
      Biopsy was carried out through the bronchoscopy, the pathological findings showed
      characteristic cribriform and tubular pattern which was formed by two-layered
      cells with ductal and myoepithelial phenotypes, which were consistent with
      adenoid cystic carcinoma. Re-examining the patient, the lung was clear without
      any wheeze when she was seated. However, inspiratory wheeze was heard in her left
      upper lung when she was supine, and disappeared after sitting up again.
      Subsequently the patient underwent a resection surgery. At the operational site,
      the tumor was seen on the anterolateral wall of the left main bronchus, without
      submucosally expanding histologically. Therefore, a sleeve resection surgery of
      the left main bronchus was performed. Following surgery, chest CT scan revealed
      complete resolution of the tumor. Her symptoms improved significantly, as did her
      pulmonary function tests, although all the medicines for asthma were stopped.
      Now, two years after the operation, the patient remained asymptomatic, and
      spirometry was performed again which showed normal completely. The presenting
      case report emphasizes the fact that not all wheezes and reversible airflow
      obstruction are asthma. It is critical to bear in mind that if a "difficult
      asthma" patient does not respond to appropriate anti-asthma therapy; localized
      obstructions should be differentiated.

PMID- 29643545
TI  - [Necessity and feasibility of data sharing of cohort studies].
AB  - Cohort study is one of the important epidemiological methods which plays an
      irreplaceable status and role in etiological study. Using cohort study design, we
      can accurately and continuously collect genetic and environmental information,
      and identify and validate omics biomarkers to provide evidences for precision
      public health and medicine. However, results from a new cohort would not be
      available for at least ten years, as five years would be needed for funding,
      planning and enrolment, and another five for following up even the earliest
      analyses of the most common diseases; results for most cancers would take longer,
      with an unaffordable budget for many research investigators or institutions. That
      brings an alternative strategy of using existing cohort studies by sharing data
      between each other. Data sharing of cohort studies would be beneficial in many
      ways. Data sharing of cohort studies has the potential to make large samples
      unattainable in a single study, increase statistical power, enable more accurate
      and detailed subgroup analysis, increase the generalizability of results. It
      would also facilitate exchange of experiences and learning from each other, avoid
      for duplicated research and effectively promote the second use of existing data
      (i.e. using old data to discover new results). The data sharing would save staff
      recruitment, follow-up, laboratory analysis of the cost, with a high cost-benefit
      returns and economies of scale. Data sharing enables cross-validation and
      repeated verification across different data. Many international research funding
      agencies or leading research groups have also reached consensus on the principles
      and goals for promoting the sharing of medical research data. Due to rapid
      development of cohort studies in the past decades, China already has the basis
      for data sharing of cohort studies. Unfortunately, most of the existing cohort
      studies are self-contained, independent, lack of visibility, with insufficient co
      operation and data sharing between each other. The academic value of the existing
      data collected in these cohort studies have not been fully exploited and utilized
      so far. Therefore, the China Cohort Consortium is trying to establish a multi
      level three-dimensional cooperation and data sharing strategy. We hope that it
      will encourage researchers from public health, clinical and other related fields
      to work more closely through providing data management, data integration, data
      interaction, tools development, data repositories and other functions.

PMID- 29643546
TI  - Partition-based ultrahigh-dimensional variable screening.
AB  - Traditional variable selection methods are compromised by overlooking useful
      information on covariates with similar functionality or spatial proximity, and by
      treating each covariate independently. Leveraging prior grouping information on
      covariates, we propose partition-based screening methods for ultrahigh
      dimensional variables in the framework of generalized linear models. We show that
      partition-based screening exhibits the sure screening property with a vanishing
      false selection rate, and we propose a data-driven partition screening framework
      with unavailable or unreliable prior knowledge on covariate grouping and
      investigate its theoretical properties. We consider two special cases:
      correlation-guided partitioning and spatial location- guided partitioning. In the
      absence of a single partition, we propose a theoretically justified strategy for
      combining statistics from various partitioning methods. The utility of the
      proposed methods is demonstrated via simulation and analysis of functional
      neuroimaging data.

PMID- 29643547
TI  - Securing of supraglottic airway devices during position change and in prone
      position.

PMID- 29643548
TI  - Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: Fluid and
      temperature remain the culprit!

PMID- 29643549
TI  - Low-flow anaesthesia - underused mode towards "sustainable anaesthesia".
AB  - Any technique that employs a fresh gas flow that is less than the alveolar
      ventilation can be classified as low-flow anaesthesia. The complexities involved
      in the calculation of uptake of anaesthetic agents during the closed-circuit
      anaesthesia made this technique less popular. However, the awareness of the
      dangers of theatre pollution with trace amounts of the anaesthetic agents and the
      prohibitively high cost of the new inhalational agents, have helped in the
      rediscovery of low-flow anaesthesia. Moreover, the time has arrived for each of
      us, the practicing anaesthesiologists, to move towards the practice of low-flow
      anaesthesia, to achieve lesser theatre and environmental pollution and also to
      make anaesthesia more economical. The article also reviews low-flow anaesthesia
      (LFA) in paediatrics, recent advances such as automated LFA and updates on
      currently undergoing research to retrieve and reuse anaesthetic agents.

PMID- 29643550
TI  - Evaluation of performance of Streamlined Liner of the Pharynx AirwayTM, Laryngeal
      Mask Airway-ProSeal and endotracheal tube in prone position: A prospective,
      randomised study.
AB  - Background and Aims: Airway used in prone position should be efficacious and
      safe. The Streamlined Liner of the Pharynx Airway (SLIPATM) and Laryngeal Mask
      Airway-ProSeal (PLMA) provide better airway seal and protection against
      aspiration. We planned to evaluate the performance of SLIPATM, PLMA and
      endotracheal tube (ETT) in prone position. Methods: 114 adult patients undergoing
      elective surgery in prone position under general anaesthesia were randomised into
      Group-T (ETT), Group-S (SLIPATM) and Group-P (PLMA). Airways were inserted in
      supine position and patients turned prone subsequently. Airway characteristics,
      ventilatory parameters and complications were noted. One-way analysis of
      variance, Mann-Whitney U-test and Chi-square or Fisher's exact test were used.
      Results: Tidal volumes, peak airway pressure and compliance were comparable at
      all times. Leak pressure was significantly higher (P < 0.001) in Group-T (mean
      leak pressure = 40 cmH2O) when compared to Group-S and Group-P at all the times
      of recording, and there was no significant difference between Group-S and Group
      P. The number of patients requiring airway/neck manipulation in prone position
      was significantly higher (P < 0.001) in Group-S (19 [55.9%]) when the three
      groups were compared (none in Group-T) and in comparison with Group-P (5 [14.7%],
      P < 0.001). On airway removal, the incidence of complications and airway reaction
      was significantly higher in Group-T. Group-S had a significantly higher incidence
      of dysphagia at 2 h postoperatively. Conclusion: ETT was most efficacious.
      SLIPATM and PLMA were efficacious, safe and less stimulating to the airway during
      removal. More patients required SLIPATM airway/neck manipulation.

PMID- 29643551
TI  - Role of dexmedetomidine as an anaesthetic adjuvant in breast cancer surgery as a
      day-care procedure: A randomised controlled study.
AB  - Background and Aims: Breast cancer surgery can be carried out as day-care
      procedure to increase patient turnover, decrease disease progression and
      financial burden. The present study was carried out to assess the role of
      dexmedetomidine in breast cancer surgery as a day-care procedure. Methods: This
      prospective randomised, double-blind study was carried out on 100 patients
      screened for day-care breast cancer surgery. They were divided into two groups of
      50 each; who received either normal saline (Group NS) or 0.6 MUg/kg/h
      dexmedetomidine (Group D) infusion from 10 min before induction until skin
      closure. All patients were given general anaesthesia. The incidence of discharge,
      post-operative pain (POP), average rescue analgesia (fentanyl) required and side
      effects were noted. Statistical analysis was performed using Student's t-test and
      Chi-square test. Results: Incidence of discharge in group NS was 60% compared to
      88% in Group D (P = 0.001). Average rescue analgesia requirement by group NS was
      136.07 +/- 43.06 MUg, whereas it was 77.5 +/- 29.86 MUg in Group D (P = 0.01).
      The incidence of POP in 6 h and within 2 h of expected discharge time in Group NS
      was 56% and 28%, respectively, and in Group D, it was 8% in both the periods (P <
      0.001 and 0.01). Side effects such as post-operative nausea, vomiting and
      bleeding were encountered in eight and two patients, respectively, in Group NS
      and two and one patients, respectively, in Group D. Conclusion: Dexmedetomidine
      as an anaesthetic adjuvant makes breast cancer surgery feasible on day-care
      basis.

PMID- 29643552
TI  - Anaesthetic management and perioperative outcomes of cytoreductive surgery with
      hyperthermic intraperitoneal chemotherapy: A retrospective analysis.
AB  - Background and Aims: Cytoreductive surgery (CRS) combined with hyperthermic
      intraperitoneal chemotherapy (HIPEC) is becoming the standard treatment option
      for peritoneal carcinomatosis but is associated with high rates of morbidity and
      mortality. Our aim was to retrospectively analyse and evaluate intra-operative
      factors associated with morbidity and mortality of CRS and HIPEC. Methods: Intra
      operative data were collected for cases done over 1 year (24 cases) and analysed
      for the primary outcome of post-operative ventilation >24 h, and secondary
      outcome of length of the Intensive Care Unit (ICU) stay >5 days. Statistical
      analysis was carried out in STATA 11 software. Results: Higher peritoneal
      carcinoma index (PCI), (P = 0.0047), longer duration of surgery (P = 0.0016),
      higher delta temperatures (P = 0.0119), increased estimated blood loss (EBL) (P =
      0.0054), high intraoperative fluid requirement (P = 0.0038), lower mean arterial
      pressure (MAP) (P = 0.0021) and higher blood products requirement were associated
      with >24 h ventilation. These factors were also associated with longer ICU stay.
      All these factors associated with >24 h ventilation and prolonged ICU stay are
      related to the PCI which is an indicator of the extent of surgery. Conclusion:
      Higher PCI, longer duration of surgery, higher delta temperatures, increased EBL,
      high intraoperative fluid requirement, lower mean arterial pressure and higher
      blood products requirement were associated with >24 h postoperative ventilation
      as well as ICU stay >5 days. All these factors are related to the PCI, which is a
      major predictor of post-operative morbidity.

PMID- 29643553
TI  - The effect of pre-emptive gabapentin on anaesthetic and analgesic requirements in
      patients undergoing rhinoplasty: A prospective randomised study.
AB  - Background and Aims: Hypotensive anaesthesia is necessary in rhinoplasty for
      better visualisation of surgical field and reduction of surgery time. Gabapentin
      is a new generation anticonvulsant with anti-hyperalgesic and anti-nociceptive
      properties. We aimed to investigate the effect of pre-operative administration of
      oral gabapentin (1200 mg) on anaesthetic requirements and post-operative
      analgesic consumption and its role in hypotensive anaesthesia for rhinoplasty.
      Methods: Seventy adult patients undergoing rhinoplasty, were randomly allocated
      to two groups. Group I (G I) (n = 35) received gabapentin 1.2 g and Group II (G
      II) (n = 35) received oral placebo capsules 2 h before surgery. General
      anaesthesia was maintained with sevoflurane in oxygen-nitrous oxide to maintain
      bispectral index value between 40 and 60, and remifentanil infusion to keep mean
      arterial pressure (MAP) at 55-60 mmHg. End-tidal sevoflurane concentration, intra
      operative remifentanil consumption and time to intended MAP were recorded. Visual
      analogue scale (VAS) scores, post-operative analgesic requirements and side
      effects for the first 24 h were recorded. Results: G I required significantly
      lower intra-operative remifentanil (G I = 0.8 +/- 0.26 mg and G II = 1.7 +/- 0.42
      mg; P = 0.001) and end-tidal sevoflurane concentration, with reduced doses of
      post-operative tramadol and diclofenac sodium. Time to the intended MAP was
      significantly less in G I than G II (59.1 +/- 12.3 vs. 73.6 +/- 16.4,
      respectively, with P = 0.001). Conclusion: Pre-operative oral gabapentin
      significantly reduced intra-operative remifentanil and sevoflurane requirements
      during hypotensive anaesthesia along with decreased post-operative analgesic
      requirement.

PMID- 29643554
TI  - Effectiveness of transnasal humidified rapid-insufflation ventilatory exchange
      versus traditional preoxygenation followed by apnoeic oxygenation in delaying
      desaturation during apnoea: A preliminary study.
AB  - Background and Aims: Transnasal humidified rapid-insufflation ventilatory
      exchange (THRIVE) during apnoea has shown to delay desaturation. The primary
      objective was to compare time to desaturate to <90% during apnoea with THRIVE
      versus traditional preoxygenation followed by apnoeic oxygenation. Methods: This
      prospective, randomised, single-blinded study was conducted in 10 adult patients
      presenting for direct laryngoscopy under general anaesthesia without endotracheal
      intubation. Group P patients were preoxygenated with 100% oxygen, and in Group H,
      high-flow humidified oxygen was delivered using nasal cannula for 3 min. After
      induction and neuromuscular blockade, time to desaturate to 90%, while receiving
      apnoeic oxygenation, was noted. Chi-square test and Mann-Whitney tests were used.
      Results: Group H had a significantly longer apnoea time as compared to Group P
      (796.00 +/- 43.36 vs. 444.00 +/- 52.56 s). All patients in Group H continued to
      have nearly 100% saturation even at 12 min of apnoea. However, in Group P, 80% of
      patients desaturated to <90% after 6 min of apnoea. Baseline blood gases, that
      following preoxygenation and at 3 min of apnoea time were comparable in both
      groups. At 6 min, Group H had a significantly higher PaO2 (295.20 +/- 122.26 vs.
      135.00 +/- 116.78) and PaCO2 (69.46 +/- 7.15 vs. 59.00 +/- 4.64). Group H
      continued to have a PaO2 of >200 mmHg even at 12 min of apnoea with a significant
      rise in PaCO2 along with fall in pH after 6 min. Conclusion: During apnoeic
      periods time to desaturate to <90% was significantly prolonged with use of
      THRIVE.

PMID- 29643555
TI  - Ultrasound guided internal jugular vein cannulation in infants: Comparative
      evaluation of novel modified short axis out of plane approach with conventional
      short axis out of plane approach.
AB  - Background and Aims: Central venous cannulation (CVC) through right internal
      jugular vein (IJV) route is routinely performed in paediatric patients undergoing
      major surgery and in those admitted to intensive care units. A novel technique
      (modified short-axis out-of-plane [MSA-OOP]) to improve first pass success rate
      of ultrasound-guided IJV CVC in neonates and infants is being compared with
      conventional SA-OOP method. Methods: A total of 120 patients were enroled in the
      study over a period of 6 months. All paediatric patients with age <1 year and
      weight <10 kg who underwent a major surgery requiring CVC were included. Patients
      were randomised to either of the two approaches of ultrasound-guided IJV
      cannulation; SA-OOP and modified SA-OOP (MSA-OOP). In modified approach, the
      midline of probe footprint was marked with a radio-opaque barium wire that casted
      a central acoustic shadow on ultrasound screen. Results: In MSA-OOP group, 83.1%
      of patients were cannulated in the first attempt as compared to 49.2% patients in
      group SA-OOP. Patients in MSA-OOP group required significantly fewer attempts for
      successful CVC as compared to patients in the SA-OOP group ( MSA-OOP: median = 1,
      interquartile range [1-1]; SAOOP: median = 2, interquartile range [1-2], P <
      0.001, Mann-Whitney U-test). Conclusion: The use of MSA-OOP ultrasound technique
      for IJV CVC cannulation results in a higher first-attempt success rate and
      reduces the number of cannulation attempts.

PMID- 29643556
TI  - A prospective observational study of injection pain in children with medium plus
      long chain triglyceride and long chain triglyceride propofol premixed with
      lignocaine.
AB  - Background and Aims: Propofol injection pain is an unresolved problem in
      children. Although medium and long chain triglyceride (MCT-LCT) propofol has
      shown promising results in adults, its efficacy in children is not proven. In a
      prospective observational study the incidence and severity of pain with MCT-LCT
      and LCT propofol in children was compared. Methods: After obtaining approval from
      the Institutional Ethics Committee, 170 children (age group 6 months to 8 years)
      scheduled for various surgeries were included in this study. Following standard
      pre-medication, propofol 1% either LCT or MCT-LCT in a dose of 2-4 mg/kg along
      with preservative-free lignocaine (2% lignocaine 1 mg in propofol 10 mg) was
      administered. The primary objective was to study injection pain on scale of 0-6.
      For children <=2 years doubling of motor event score (0-3) and for children >2
      years, addition of motor (0-3) and verbalisation scores (0-3) were considered.
      Mann-Whitney U test was used for statistical analysis. Results: MCT-LCT group had
      lower incidence of pain (17 patients (20%) versus 35 patients (35.3%), P = 0.026)
      and severe pain (zero patients (0%) versus six patients (7.1%), P = 0.029) as
      compared to LCT group. MCT-LCT group had significantly lower mean rank of motor
      (79.65 versus 91.35), verbal (77.29 versus 90.79) and total score (77.76 versus
      93.24) as compared to LCT group (P = 0.037, 0.002, and 0.009, respectively).
      Conclusion: MCT-LCT propofol is associated with significantly lower injection
      pain as compared to LCT propofol in children, when both are combined with
      lignocaine.

PMID- 29643557
TI  - Reversal agents: do we need to administer with neuromuscular monitoring - an
      observational study.
AB  - Background and Aims: In clinical practice, in the majority of patients, recovery
      from the effect of muscle relaxants is assessed using subjective methods such as
      head lift, eye-opening, or by sustained hand grip after giving
      anticholinesterases (neostigmine) at the end of surgery. We planned a prospective
      observational cohort study to test the hypothesis that objective neuromuscular
      monitoring can help us in avoiding the use of anticholinesterases for reversal.
      Methods: The patients posted for surgery of <2 h duration were included in the
      study. The cohort of patients was formed on the basis of those who were exposed
      to objective neuromuscular monitoring of recovery (train-of-four [TOF] ratio of
      0.9 or more; exposed group) and the patients who were not exposed to objective
      neuromuscular monitoring (non-exposed group) acting as a control. Using objective
      neuromuscular monitoring, the time required for recovery from muscle relaxation
      when neostigmine was not given for reversal was noted and it was then compared
      with that of the control group. Results: A total of 190 patients were enrolled
      over a period of 3 years. With the use of TOF ratio of 0.9 for extubation,
      patients safely recovered from neuromuscular blockade, without using neostigmine,
      with no difference in the mean recovery time (14.48 +/- 1.138 min) as compared to
      the control group (12.14 +/- 1.067 min, P = 0.139). There was no incidence of
      reintubation in post-operative period. Conclusion: With objective neuromuscular
      monitoring, we can ensure complete recovery from the neuromuscular blockade while
      avoiding the use of anticholinesterases.

PMID- 29643558
TI  - Perioperative concerns and management of pressurised intraperitoneal aerosolised
      chemotherapy: Report of two cases.
AB  - Pressurised intraperitoneal aerosolised chemotherapy (PIPAC) is a new, mostly
      supportive approach to help patients with advanced peritoneal metastasis to
      increase the lifespan. It carries occupational hazards to health-care workers and
      especially anaesthesiologist during the procedure. The aerosolised chemotherapy
      can also cause chemical peritonitis and organ dysfunction in the perioperative
      period. In this case report, we present the report of two cases and discuss the
      perioperative concerns and management related to PIPAC.

PMID- 29643559
TI  - Appropriate angled-tip front width facilitates tracheal tube introducer placement
      in difficult-to-displace epiglottis situations.
AB  - Tracheal tube introducers (TTIs) are a useful aid to a conventional laryngoscopy
      intubation method of upper airway access in adults. However, even when TTIs are
      used, successful tracheal intubation is not guaranteed. Apart from suboptimal
      practice proficiency and unavailability of the complete repertoire of TTI, the
      physical attributes of the TTI have a role to play. Our report on the management
      of two cases highlights the importance of selecting a TTI with appropriate angled
      tip characteristics to facilitate successful guided intubation.

PMID- 29643560
TI  - The utility of the oxygen reserve indexTM in a neonate undergoing re-exploration
      of a tracheoesophageal fistula.

PMID- 29643561
TI  - Kawasaki disease and general anaesthesia: The Know - Hows.

PMID- 29643562
TI  - WhatsApp: Is it a solution to daily human resources management in institutional
      practice?

PMID- 29643563
TI  - Induction of anaesthesia in cyanotic heart diseases: 'Ketomidate' to the rescue!

PMID- 29643564
TI  - Acute exacerbation of Chiari malformation: A rare cause for non-awakening from
      anaesthesia.

PMID- 29643565
TI  - Scavenging tubing compression: A rare cause for anaesthesia ventilator
      malfunction.

PMID- 29643566
TI  - Only with an optimal position of the supraglottic airway in situ, valid
      conclusions can be drawn about oropharyngeal airway pressure.

PMID- 29643567
TI  - Reply: Only with an optimal position of the supraglottic airway in situ, valid
      conclusions can be drawn about oropharyngeal airway pressure.

PMID- 29643568
TI  - Electromagnetic scattering and emission by a fixed multi-particle object in local
      thermal equilibrium: General formalism.
AB  - The majority of previous studies of the interaction of individual particles and
      multi-particle groups with electromagnetic field have focused on either elastic
      scattering in the presence of an external field or self-emission of
      electromagnetic radiation. In this paper we apply semi-classical fluctuational
      electrodynamics to address the ubiquitous scenario wherein a fixed particle or a
      fixed multi-particle group is exposed to an external quasi-polychromatic
      electromagnetic field as well as thermally emits its own electromagnetic
      radiation. We summarize the main relevant axioms of fluctuational
      electrodynamics, formulate in maximally rigorous mathematical terms the general
      scattering-emission problem for a fixed object, and derive such fundamental
      corollaries as the scattering-emission volume integral equation, the Lippmann
      Schwinger equation for the dyadic transition operator, the multi-particle
      scattering-emission equations, and the far-field limit. We show that in the
      framework of fluctuational electrodynamics, the computation of the self-emitted
      component of the total field is completely separated from that of the elastically
      scattered field. The same is true of the computation of the emitted and
      elastically scattered components of quadratic/bilinear forms in the total
      electromagnetic field. These results pave the way to the practical computation of
      relevant optical observables.

PMID- 29643569
TI  - Maintaining Atmospheric Mass and Water Balance in Reanalyses.
AB  - This study describes the modifications made to the Goddard Earth Observing System
      (GEOS) Atmospheric Data Assimilation System (ADAS) to conserve atmospheric dry
      air mass and to guarantee that the net source of water from precipitation and
      surface evaporation equals the change in total atmospheric water. The
      modifications involve changes to both the atmospheric model and the analysis
      procedure. In the model, sources and sinks of water are included in the
      continuity equation; in the analysis, constraints are imposed to penalize (and
      thus minimize) analysis increments of dry-air mass. Finally, changes are also
      required to the Incremental Analysis Update (IAU) procedure. The effects of these
      modifications are separately evaluated in free-running and assimilation
      experiments. Results are also presented from a multiyear reanalysis (Version 2 of
      the Modern Era Retrospective-Analysis for Research and Applications: MERRA-2)
      that uses the modified system.

PMID- 29643570
TI  - Benefits and Pitfalls of GRACE Data Assimilation: a Case Study of Terrestrial
      Water Storage Depletion in India.
AB  - This study investigates some of the benefits and drawbacks of assimilating
      Terrestrial Water Storage (TWS) observations from the Gravity Recovery and
      Climate Experiment (GRACE) into a land surface model over India. GRACE observes
      TWS depletion associated with anthropogenic groundwater extraction in northwest
      India. The model, however, does not represent anthropogenic groundwater
      withdrawals and is not skillful in reproducing the interannual variability of
      groundwater. Assimilation of GRACE TWS introduces long-term trends and improves
      the interannual variability in groundwater. But the assimilation also introduces
      a negative trend in simulated evapotranspiration whereas in reality
      evapotranspiration is likely enhanced by irrigation, which is also unmodeled.
      Moreover, in situ measurements of shallow groundwater show no trend, suggesting
      that the trends are erroneously introduced by the assimilation into the modeled
      shallow groundwater, when in reality the groundwater is depleted in deeper
      aquifers. The results emphasize the importance of representing anthropogenic
      processes in land surface modeling and data assimilation systems.

PMID- 29643571
TI  - A General CT Reconstruction Algorithm for Model-Based Material Decomposition.
AB  - Material decomposition in CT has the potential to reduce artifacts and improve
      quantitative accuracy by utilizing spectral models and multi-energy scans. In
      this work we present a novel Model-Based Material Decomposition (MBMD) method
      based on an existing iterative reconstruction algorithm derived from a general
      non-linear forward model. A digital water phantom with inserts containing
      different concentrations of calcium was scanned on a kV switching system. We used
      the presented method to simultaneously reconstruct water and calcium material
      density images, and compared the results to an image domain and a projection
      domain decomposition method. When switching voltage every other frame, MBMD
      resulted in more accurate water and calcium concentration values than the image
      domain decomposition method, and was just as accurate as the projection domain
      decomposition method. In a second, slower, kV switching scheme (changing voltage
      every ten frames) which precluded the use of traditional projection domain based
      methods, MBMD continued to produce quantitatively accurate reconstructions.
      Finally, we present a preliminary study applying MBMD to a water phantom
      containing vials of different concentrations of K2HPO4 which was scanned on a
      cone-beam CT test bench. Both the fast and slow (emulated) kV switching schemes
      resulted in similar reconstructions, indicating MBMD's robustness to challenging
      acquisition schemes. Additionally, the K2HPO4 concentration ratios between the
      vials were accurately represented in the reconstructed K2HPO4 density image.

PMID- 29643572
TI  - Working in the Shadows: Safety and Health in Forestry Services in Southern
      Oregon.
AB  - We conducted a small participatory survey to document occupational injuries and
      illnesses, medical treatment, wage issues, and general working conditions among
      150 forest workers in southern Oregon who are mostly Spanish-speaking immigrants
      from Latin America. We used snowball sampling in administering the survey. Survey
      results showed a high rate of job-related injury among the workers who responded
      to our survey. Results also suggested that many forestry services contractors
      licensed in Jackson and Josephine counties may not always follow labor laws. The
      vast majority of workers surveyed reported being fearful of retaliation for
      reporting injuries. There were no differences in reported working conditions and
      wage issues between workers with H-2B visas and other workers in the sample. This
      finding suggests that current US labor and health and safety laws are not
      effectively protecting Oregon's forest workers, owing to forest workers'
      structural vulnerability-their low positioning in social structures supported by
      immigration and economic status-compounded by fear of retaliation. Immigration
      policies and enforcement practices that contribute to creating a labor system
      with these inherent vulnerabilities and power imbalances need to be further
      examined and changed.

PMID- 29643573
TI  - Beyond polarization: using Q methodology to explore stakeholders' views on
      pesticide use, and related risks for agricultural workers, in Washington State's
      tree fruit industry.
AB  - Controversies in food and agriculture abound, with many portrayed as conflicts
      between polarized viewpoints. Framing such controversies as dichotomies, however,
      can at times obscure what might be a plurality of views and potential common
      ground on the subject. We used Q methodology to explore stakeholders' views about
      pesticide safety, agricultural worker exposure, and human health concerns in the
      tree fruit industry of central Washington State. Using a purposive sample of
      English and Spanish-speaking agricultural workers, industry representatives,
      state agencies, educators, and advocates (n = 41), participants sorted 45
      statements on pesticide use and perceived human safety risks in the tree fruit
      industry in 2011. We used PQMethod 2.33 statistical software program to identify
      viewpoints, based on differences between how participants sorted the statements.
      The results revealed three distinct viewpoints among 38 sorters that explained 52
      percent of the variance. The viewpoints included the: (1) skeptics (n = 22) who
      expressed concern over the environmental and human health impacts of pesticide
      use; (2) acceptors (n = 10) who acknowledged inherent risks for using pesticides
      but saw the risks as known, small and manageable; and (3) incrementalists (n = 6)
      who prioritized opportunities to introduce human capital and technological
      improvements to increase agricultural worker safety. We then brought
      representatives with these different viewpoints together to analyze the results
      of the Q study, and to brainstorm mutually acceptable improvements to health and
      safety in tree fruit orchards. In describing and analyzing this case study, we
      argue that Q methodology can serve as one potentially effective tool for
      collaborative work, in this case facilitating a process of orchard safety
      improvements despite perceived stakeholder polarization.

PMID- 29643574
TI  - The effectiveness of raising the heel height of shoes to reduce heel pain in
      patients with calcaneal spurs.
AB  - [Purpose] To investigate the effect of heel height on the distribution of plantar
      foot force and heel pain in patients with a heel spur. [Subjects and Methods]
      Plantar force was measured using 8 force sensors in 16 patients (3 men, 13
      women), with symptomatic heel spur for 4 heel heights (0-4 cm). Sensors were
      located at the hallux (T1); medial to lateral metatarsals (M1 through M3), mid
      foot (MF); and at the central, lateral, and medial heel (CH, LH, and MH). Pain
      was evaluated using the minimum compression force that caused pain and was
      measured using an algometer. [Results] Load bearing shifted from the heel (CH) to
      the mid-foot (MF) and hallux (T1) with increasing heel height. Raising the heel
      from 2 to 3 cm reduced the magnitude of load bearing, relative to the minimum
      compression force for pain, by 3.70% at the LH and 2.35% at the MH. Excellent
      clinical outcomes, defined by a 70-100% decrease in pain, were achieved in 10/16
      participants with the use of a 2-cm and 3-cm heel height in men and women,
      respectively. [Conclusion] Increasing heel height effectively decreases the
      plantar force on the heel during weight-bearing activities.

PMID- 29643575
TI  - Difference in tongue strength using visual feedback in healthy adults.
AB  - [Purpose] This study investigated the difference in tongue strength with and
      without visual feedback in healthy adults. [Subjects and Methods] A total of 30
      healthy adults were recruited. We measured the strength of the anterior region of
      the tongue before and after applying visual feedback using the Iowa Oral
      Performance Instrument. [Results] The tongue strength was measured as 45.5 +/-
      9.3 kilopascals with visual feedback and 41.1 +/- 8.6 kilopascals without visual
      feedback, showing a statistically significant difference. [Conclusion] Visual
      feedback may be an effective tool for increasing the strength of the tongue.

PMID- 29643576
TI  - Upper extremity resistance exercise with elastic bands for respiratory function
      in children with cerebral palsy.
AB  - [Purpose] We investigated the effects of upper extremity resistance exercise with
      elastic bands on respiratory function in children with cerebral palsy. [Subjects
      and Methods] Fifteen children were divided into two groups: the experimental
      (n=8) and control (n=7) groups. Both groups performed general exercises for 30
      minutes per session, two times a week during the intervention period. The
      experimental group performed an additional upper extremity resistance exercise
      with elastic bands for 20-30 minutes per session, twice weekly for 8 weeks.
      Pulmonary function, and respiratory muscle and grip strength were measured before
      and after the exercise. [Results] There was no significant difference in forced
      vital capacity, forced expiratory volume in one second, the ratio of forced
      expiratory volume in one second to forced vital capacity, and peak expiratory
      flow before and after the intervention in either group. The increment of maximal
      expiratory pressure was significantly greater in the experimental group, compared
      with the control group. In addition, grip strength was significantly increased in
      the experimental group after the intervention than before. [Conclusion] We found
      that upper extremity resistance exercise with elastic bands has a positive effect
      on expiration and improves grip strength in children with cerebral palsy.

PMID- 29643577
TI  - Effects of concentric contraction of the wrists and transcutaneous electrical
      nerve stimulation cycle on pain and muscle strength in lateralepicondylitis
      patients.
AB  - [Purpose] This study examined the effects of transcutaneous electrical nerve
      stimulation and concentric contraction of the muscles surrounding the elbow
      joints on pain and muscular strength in the elbow joints of patients with lateral
      epicondylitis. [Subjects and Methods] The subjects of this study were 30 patients
      who visited our hospital with the main complaint of lateral pain in the elbow
      joint. All subjects were randomly and equally assigned to an experimental group
      that conducted concentric contraction exercises in sync with a transcutaneous
      electrical nerve stimulation cycle and a control group that performed concentric
      contraction after the application of transcutaneous electrical nerve stimulation.
      Patients used a 10 cm visual analogue scale to evaluate the level of pain in
      their elbow joints. To measure the strength of muscles around the elbow joints,
      the subjects' paretic grip strength was measured using an electronic grip
      strength dynamometer. [Results] No statistically significant difference in visual
      analog scale was found between the two groups. Regarding changes in grip
      strength, changes in the experimental group's grip strength were significantly
      greater than those in the control group. [Conclusion] These results can be used
      as a basis for reducing pain and improving strength in lateral epicondylitis
      patients.

PMID- 29643578
TI  - Effect of mirror therapy and electrical stimulation on upper extremity function
      in stroke with hemiplegic patient: a pilot study.
AB  - [Purpose] This study investigated the effects of mirror therapy and neuromuscular
      electrical stimulation on upper extremity function in stroke patients. [Subjects
      and Methods] This study recruited 8 stroke patients. All patients were treated
      with mirror therapy and neuromuscular electrical stimulation five times per week
      for 4 weeks. Upper limb function evaluation was performed using upper extremity
      part of fugl meyer assessment. [Results] Before and after intervention, fugl
      meyer assessment showed significant improvement. [Conclusion] In this study,
      mirror therapy and neuromuscular electrical stimulation are effective methods for
      upper extremity function recovery in stroke patients.

PMID- 29643579
TI  - The effect of ball exercise on the balance ability of young adults.
AB  - [Purpose] The aim of this study was to investigate the effects of static and
      dynamic balance by using Medicine-ball and Swiss-ball exercises. [Subjects and
      Methods] Thirty-six normal adults who agreed to participate were included in the
      study. Subjects were randomly assigned to the Medicine-ball (n=18) and Swiss-ball
      groups (n=18). The participants performed the exercise for 6 weeks. Balance error
      scoring system and one leg standing test were performed to determine static
      balance, and functional reach test and timed up and go test were performed to
      determine dynamic balance. [Results] A significant improvement was observed from
      the Medicine-ball and Swiss-ball exercises, but no difference was found between
      the groups. In addition, a significant difference was found between balance error
      scoring system, one leg standing test and functional reach test after pre- and
      post-exercise of the Medicine-ball and Swiss-ball. [Conclusion] The findings of
      this study showed that the Medicine-ball and Swiss-balls were effective in
      improving static and dynamic balance.

PMID- 29643580
TI  - Effect of various wheelchair handle grip directions on muscle activities of upper
      body of assistant during movement on ascending and descending ramps.
AB  - [Purpose] This study aims to determine the effects of various wheelchair handle
      grip directions on the muscle activities of the upper body of an assistant during
      movement on ascending and descending ramps. [Subjects and Methods] The study
      subjects were 17 young and healthy participants whose mean age, height, and
      weight was 23.0 +/- 2.7 years, 175.5 +/- 4.7 cm, and 70.0 +/- 14.2 kg,
      respectively; all subjects voluntarily consented to participate. Three grip
      directions were tested: general grip, medial grip, and neutral grip. Muscle
      activities in the serratus anterior, rhomboid, erector spine, biceps brachii,
      triceps brachii, bracioradialis, flexor carpi radialis, and extensor carpi
      radialis were measured using an electromyograph (EMG). [Results] Significant
      differences were seen in the muscle activities of the biceps brachii,
      bracioradialis, and flexor carpi radialis during wheelchair movement on an
      ascending ramp and in the biceps brachii and triceps brachii during movement on a
      descending ramp. [Conclusion] Measurement results showed that the general grip
      resulted in the highest muscle activities in the upper body of assistants during
      wheelchair movement on both ascending and descending ramps.

PMID- 29643581
TI  - Hypervigilance to pain affects activities of daily living: an examination using
      the Japanese version of the pain vigilance awareness questionnaire.
AB  - [Purpose] Hypervigilance to pain is an important aspect of the fear-avoidance
      model of pain that may be associated with disability more than other
      psychological factors examined. The aim of the study was to investigate how
      hypervigilance to pain influences disability compared with other psychological
      factors examined. [Subjects and Methods] The subjects of this study were 50
      elderly patients with chronic pain (7 men and 43 women, 80.3 +/- 7.8 years). To
      assess the pain level, the Numerical Rating Scale (NRS) was used. To assess
      psychological factors, the Hospital Anxiety and Depression Scale (HADS), the
      Tampa Scale for Kinesiophobia (TSK), the Pain Catastrophizing Scale (PCS), and
      the Pain Vigilance Awareness Questionnaire (PVAQ) were used. To assess activities
      of daily living, the Pain Disability Assessment Scale (PDAS) was used. A multiple
      regression analysis (stepwise method) was performed with the PDAS as the
      dependent variable, and the NRS, HADS-anxiety, HADS-depression, TSK, PCS
      rumination, PCS-magnification, PCS-helplessness, and PVAQ, as the independent
      variables. [Results] The results of a multiple regression analysis showed that
      the PDAS scores were affected by the PVAQ and NRS scores. [Conclusion]
      Hypervigilance influenced disability more than other psychological factors
      examined.

PMID- 29643582
TI  - The effect of balance exercises and computerized cognitive training on
      psychomotor performance in elderly.
AB  - [Purpose] The purpose of this study was to investigate the effect of balance and
      computerized cognitive training on psychomotor performance in elderly females.
      [Subjects and Methods] Twentynine elderly females with the mean age of 63-71
      years old were applied voluntarily and randomly allocated to four groups: balance
      training (3 d/wk for 12 wk), balance training with computerized cognitive
      training (3 d/wk for 12 wk), computerized cognitive training group and control
      group. Psychomotor performance of all subjects was measured by Vienna Test System
      which was a computerized psychological assessment tool. Determination test (DT)
      and Visual Pursuit Test (VPT) were used as indexes of psychomotor performance.
      [Results] The results suggested that DT and VPT were significantly improved in
      all experimental groups with greater improvement in the balance supplemented with
      computerized cognitive training group. [Conclusion] Balance training and
      computerized cognitive are highly recommended in elderly with the aim of
      increasing cognitive performance.

PMID- 29643583
TI  - Difference between tablet methods and paper questionnaire methods of conducting a
      survey with community-dwelling elderly.
AB  - [Purpose] This study aimed to develop a tablet app that emulates paper
      questionnaires used in clinical care, and to verify the difference between the
      utility of tablet survey methods and paper questionnaire methods with elderly
      people. [Subjects and Methods] A tablet app was developed in the Java language. A
      questionnaire was provided to 30 community-dwelling elderly people. The subjects
      were randomly allocated to the group responding on the tablet (tablet group) or
      that responding to a paper-based questionnaire (questionnaire group). Assessed
      items included response time to questions, whether or not they had queries
      regarding the survey, and data input time. For the tablet group, a questionnaire
      was conducted regarding the operability of the tablet. [Results] There was no
      difference in response time between the two groups. Significantly more people in
      the tablet group had queries regarding the survey. Data input time was 426
      seconds for the tablet group and 1268 seconds for the questionnaire group. In the
      survey regarding tablet operability, there were no negative opinions about the
      visibility of the screen. [Conclusion] Tablets can be used with elderly people to
      shorten the data input time. The present findings suggested that tablet surveys
      could be effective for a large-scale investigation.

PMID- 29643584
TI  - Effects of virtual reality intervention on upper limb motor function and activity
      of daily living in patients with lesions in different regions of the brain.
AB  - [Purpose] This study aimed to investigate whether a virtual reality (VR)
      intervention has an influence in improving the motor function and activities of
      daily living (ADLs) in patients with lesions in different regions of the brain.
      [Subjects and Methods] Eleven subjects with hemiplegic stroke were recruited in
      this study, which was conducted from January to February, 2017. They received a
      VR intervention once a day for 30 min, 5 times a week for 4 weeks. The Fugl-Meyer
      Assessment (FMA) and the Korean version of the Modified Barthel Index (K-MBI)
      were used to assess the post-stroke patients' motor function and ADLs,
      respectively. [Results] There were significant differences in pre- and post-test
      outcomes of the Arm and Coordination and Speed (CS) in the FMA and K-MBI in the
      middle cerebral artery group (MCAG). Moreover, there were significant differences
      in all sub-tests of FMA and K-MBI in the Basal ganglia group (BGG). In addition,
      there were significant differences in the pre-test outcomes of Arm and pre- and
      post-test outcomes of Hand in the FMA between the two groups. [Conclusion] This
      study revealed that VR intervention improved the upper limb motor function and
      ADLs of post-stroke patients, especially those in the BGG.

PMID- 29643585
TI  - Electromyographic evaluation of a low-level laser protocol for the treatment of
      temporomandibular disorder: a randomized, controlled, blind trial.
AB  - [Purpose] Problems involving the temporomandibular joint and associated
      structures can lead to temporomandibular disorder (TMD). The aim of the present
      study was to evaluate muscle activity in individuals with a diagnosis of TMD
      before and after treatment with low-level laser therapy (LLLT) through the use of
      electromyography (EMG). [Subjects and Methods] Male and female individuals aged
      14 to 23 years were evaluated. TMD was determined by a clinical examination and
      the administration of the Research Diagnostic Criteria for Temporomandibular
      Disorders, followed by the evaluation of sensitivity to palpation of the masseter
      and anterior temporal muscles as well as the EMG determination of muscle
      activity. The participants were randomly allocated to an active LLLT group (n=9)
      and sham group (n=7). Twelve sessions of LLLT were conducted using a wavelength
      of 780 nm, energy density of 25 J/cm2, power of 50 mW, power density of 1.25
      W/cm2 and a 20-second exposure time or sham LLLT. Muscle activity was determined
      prior to treatment and after the last session. [Results] During the isometric
      evaluation of the masseter and anterior temporal muscles, an increase in the mean
      EMG signal was found in the group submitted to active LLLT. When evaluated
      individually, some participants in the active LLLT group demonstrated a reduction
      in muscle activity, but no significant differences were found in the mean EMG
      signal between the initial and final evaluations. [Conclusion] Further studies
      with a larger sample size are needed to confirm the present findings.

PMID- 29643586
TI  - Efficacy of exercise on pelvic pain and posture associated with endometriosis:
      within subject design.
AB  - [Purpose] This study was carried out to determine the effect of an exercise
      program on pelvic pain and posture associated with endometriosis. [Subjects and
      Methods] This study was designed as repeated measures design that compared one
      group of 20 patients (age range 26-32 years) diagnosed by laparoscope as having
      mild or moderate endometriosis before, after 4 weeks, and after 8 weeks of
      exercise program. The exercise program parameters were based on the American
      College of Obstetricians and Gynecologists guidelines for exercise suitable for
      sedentary women. To assess the intensity of endometriosis pain, a present pain
      intensity scale was used. On the other hand, a raster stereography system was
      used to assess the posture. [Results] After 8 weeks of performing the exercise
      regimen, there was a statistically significant decrease in the patients' pain
      intensity and thoracic kyphosis angle program in compared with pre treatment.
      [Conclusion] Ultimately it was proven that eight weeks of an exercise program is
      very effective in decreasing pain and postural abnormalities associated with
      endometriosis.

PMID- 29643587
TI  - Relationship of white matter lesions and severity of pushing behavior after
      stroke.
AB  - [Purpose] The relationship between white matter lesions (WMLs) and pushing
      behavior (PB) is still poorly understood. The purpose of this study was to
      investigate whether damage from WMLs affects the functional outcome of PB after
      acute stroke. [Subjects and Methods] In total, 37 patients were included. PB was
      assessed using the standardized Scale for Contraversive Pushing (SCP). Stroke
      types were classified as total anterior circulation infarct (TACI), partial
      anterior circulation infarct (PACI), or lacunar syndrome using the Bamford
      classification. WML severity was categorized into four groups using the Fazekas
      visual scale. Thereafter, patients were divided into 4 groups according to the
      stroke type and/or presence of WMLs. The SCP, Trunk Control Test (TCT), Stroke
      Impairment Assessment Set (SIAS), and Barthel Index were the outcome measures.
      [Results] The SCP and TCT in patients with PACI without WMLs were better than
      those in patients with TACI with or without WMLs. Regarding SCP, TCT, and SIAS,
      patients with TACI had poorer values compared with PACI, regardless of WML
      severity. Barthel Index efficiency was not significantly different between the
      groups. [Conclusion] Our results suggest that moderate to severe WMLs and PACI
      had a relationship with PB severity and truncal balance.

PMID- 29643588
TI  - Effect of lumbar stabilization exercise on disc herniation index, sacral angle,
      and functional improvement in patients with lumbar disc herniation.
AB  - [Purpose] This study aimed to examine the effects of pelvic movements on the back
      function of patients with lumbar disc herniation when lumbar stabilization
      exercise was applied to the patients, suggest an intervention method that can be
      used in future clinical therapies. [Subjects and Methods] Thirty patients with
      lumbar disc herniation underwent the intervention 30 minutes per day, three times
      per week for 4 weeks. Of them, 15 patients were assigned to the balance center
      stabilization resistance exercise group (experimental group I) and the other 15
      were assigned to the three-dimensional stabilization exercise group (experimental
      group II). Before the intervention, disc herniation index was measured using
      magnetic resonance imaging, sacral angle was measured using X-ray, and back
      function was measured using the KODI. Four weeks later, these three factors were
      re-measured and analyzed. [Results] There was a significant pre- versus post
      intervention difference in disc herniation index, sacral angle, and KODI in
      experimental group I and a significant difference in disc herniation index and
      KODI in experimental group II, and each group of disc herniation index and sacral
      angle had a significant difference. In experimental group I, each disc herniation
      index and sacral angle had a negative correlation. [Conclusion] The lumbar
      stabilization exercise, which controls balance using pelvic movements, improves
      mobility and stability of the sacroiliac joint; therefore, it increases pelvic
      and back movements. These kinds of movements not only improved proprioception
      sense, they also had positive effects on lumbar disc function recovery.

PMID- 29643589
TI  - Exercise intervention implemented by trained volunteers improves health-related
      quality of life among Japanese community-dwelling older females: an intervention
      study.
AB  - [Purpose] This study aimed to evaluate the sustainability and efficacy of
      exercise intervention, as implemented by professionally trained volunteers, on
      the health-related quality of life among Japanese community-dwelling older
      females. [Subjects and Methods] We conducted a non-randomized observational
      prospective study of a six-month exercise intervention delivered by volunteers or
      health professionals. Health-related quality of life was scored using the Short
      Form 36 Health Survey before and after the intervention. Participants were
      classified into three groups, comprising those with improved health, maintained
      health, and reduced health. [Results] Among 127 Japanese community-dwelling
      females aged >65 years, 50 of 62 (80.6%) females involved in the intervention
      conducted by volunteers, and 55 of 65 (84.6%) females involved in the
      intervention conducted by health professionals, completed the six-month
      intervention program. Scoring revealed that interventions by both volunteers and
      health professionals had a maintaining or improving effect on scores in >70% of
      participants instead of an expected six-month aging decline. [Conclusion]
      Exercise intervention by trained volunteers was sustainable and effective for
      improving the health-related quality of life among Japanese community-dwelling
      older females. Professionally trained volunteers could benefit communities in
      helping older persons avoid the need for daily nursing care through promoting
      health activities.

PMID- 29643590
TI  - Immediate effects of transcutaneous electrical nerve stimulation on six-minute
      walking test, Borg scale questionnaire and hemodynamic responses in patients with
      chronic heart failure.
AB  - [Purpose] This study examined the immediate effects of transcutaneous electrical
      nerve stimulation on a six-minute walking test, Borg scale questionnaire and
      hemodynamic responses in patients with chronic heart failure. [Subjects and
      Methods] Thirty patients with stable systolic chronic heart failure came to the
      pathophysiology laboratory three times. The tests were randomly performed in
      three sessions. In one session, current was applied to the quadriceps muscles of
      both extremities for 30 minutes and a six-minute walking test was performed
      immediately afterward. In another session, the same procedure was followed except
      that the current intensity was set to zero. In the third session, the patients
      walked for six minutes without application of a current. The distance covered in
      each session was measured. At the end of each session, the subjects completed a
      Borg scale questionnaire. [Results] The mean distance traveled in the six-minute
      walking test and the mean score of the Borg scale questionnaire were
      significantly different across sessions. The mean systolic and diastolic
      pressures showed no significant differences across sessions. [Conclusion] The
      increase in distance traveled during the six-minute walking test and decrease in
      fatigue after the use of current may be due to a decrease in sympathetic
      overactivity and an increase in peripheral and muscular microcirculation in these
      patients.

PMID- 29643591
TI  - Immediate effect of transcranial direct current stimulation combined with
      functional electrical stimulation on activity of the tibialis anterior muscle and
      balance of individuals with hemiparesis stemming from a stroke.
AB  - [Purpose] The aim of the present study was to evaluate the immediate effects of
      transcranial direct current stimulation (tDCS) and functional electrical
      stimulation (FES) on activity of the tibialis anterior muscle (TA) and static
      balance of individuals with hemiparesis stemming from stroke. [Subjects and
      Methods] A randomized, double-blind, crossover, clinical trial conducted with 30
      individuals with chronic post-stroke hemiparesis. Median frequency of electrical
      activity of the TA were determined using electromyography in five contractions
      concentrics and Static balance (body sway velocity and frequency), both before
      and immediately after the intervention. The participants were submitted to four
      20-minute intervention protocols with 48-hour interval: anodal tDCS + sham FES;
      sham tDCS + active FES; anodal tDCS + active FES and sham tDCS + sham FES. Anodal
      tDCS was administered over C3 or C4, the cathode was positioned in the
      supraorbital region on the contralateral side and FES was administered to the
      affected TA. [Results] No significant differences among the protocols were found
      regarding electrical activity of the TA and static balance. [Conclusion] The
      results demonstrate that tDCS alone or in combination with FES had no immediate
      effect on electrical activity of the TA and static balance of the 30 individuals
      analyzed.

PMID- 29643592
TI  - Does trampoline or hard surface jumping influence lower extremity alignment?
AB  - [Purpose] To determine whether repetitive trampoline or hard surface jumping
      affects lower extremity alignment on jump landing. [Subjects and Methods] Twenty
      healthy females participated in this study. All subjects performed a drop
      vertical jump before and after repeated maximum effort trampoline or hard surface
      jumping. A three-dimensional motion analysis system and two force plates were
      used to record lower extremity angles, moments, and vertical ground reaction
      force during drop vertical jumps. [Results] Knee extensor moment after trampoline
      jumping was greater than that after hard surface jumping. There were no
      significant differences between trials in vertical ground reaction force and
      lower extremity joint angles following each form of exercise. Repeated jumping on
      a trampoline increased peak vertical ground reaction force, hip extensor, knee
      extensor moments, and hip adduction angle, while decreasing hip flexion angle
      during drop vertical jumps. In contrast, repeated jumping on a hard surface
      increased peak vertical ground reaction force, ankle dorsiflexion angle, and hip
      extensor moment during drop vertical jumps. [Conclusion] Repeated jumping on the
      trampoline compared to jumping on a hard surface has different effects on lower
      limb kinetics and kinematics. Knowledge of these effects may be useful in
      designing exercise programs for different clinical presentations.

PMID- 29643593
TI  - Characteristics associated with freezing of gait in actual daily living in
      Parkinson's disease.
AB  - [Purpose] Parkinson's disease (PD) patients often freeze in actual daily living
      but seldom in clinical setting. This study aimed to identify the factors
      contributing to freezing of gait (FOG). [Subjects and Methods] The participants
      included 28 adults with PD. Principal component analysis was used to investigate
      the characteristics of 14 common FOG situations adopted from previous studies.
      Cluster analysis classified the subjects into four groups. Kruskal-Wallis test
      was performed to compare the PD Questionnaire-39 mobility dimension between the
      groups. [Results] The major variables of the first principal component in 14 FOG
      situations were unfamiliar places, unpredictable schedule changes, entering an
      automatic door, when another person suddenly crossed, and change in the walking
      surface. These situations were unrelated to the second principal component.
      Getting on/off a public transport and crowded places were major variables for the
      second principal component, and related to both the first and second principal
      components. Although fatigue was the most frequent FOG situation, not all
      principal components were influenced. The values of the PD Questionnaire-39
      revealed significant differences between the groups. [Conclusion] Actual FOG
      situations may be categorized into (1) task complexity, (2) both task complexity
      and emotional factors, and (3) fatigue as decreased attentional resources.

PMID- 29643594
TI  - The effect of a VR exercise program on falls and depression in the elderly with
      mild depression in the local community.
AB  - [Purpose] The purpose of this study is to explore the effect of a VR exercise
      program on falls and depression in the elderly with mild depression who reside in
      the local community. [Subjects and Methods] This study was performed by targeting
      15 elderly subjects with mild depression who resided in the local community. The
      targeted subjects voluntarily selected 3 VR exercise programs (each lasting 10
      minutes) among 4 activities, and a resting time of 5 minutes was given for an
      interval after each activity. The VR exercise program was performed for total 12
      weeks (36 times), 3 times a week, 45 minutes per session. [Results] After
      exercise, scores of static balance test (anteroposterior), Falls Efficacy Scale,
      and the Activities-specific Balance Confidence Scale in the test subjects were
      improved and depression and internal stress scores were significantly decreased
      after the intervention. [Conclusion] It can be concluded that the VR exercise
      program exerts a positive effect not only on the physical factor but also on the
      mental factor of the elderly subjects with mild depression who reside in the
      local community. It is expected that based on the VR exercise program,
      diversified home programs for the elderly should be developed in the future.

PMID- 29643595
TI  - Gender differences in joint torque focused on hip internal and external rotation
      during a change in direction while walking.
AB  - [Purpose] To investigate lower-extremity joint torque during walking direction
      changes, focused on gender differences in pelvic width. [Subjects and Methods]
      Healthy males and females (n=10) changed direction while walking by side-stepping
      (SS) and crossover stepping (CS), stepping the left leg to the left or right,
      respectively, over the right leg. Movements were recorded using four infrared
      cameras, and ground reaction force of each lower extremity measured using two
      force platforms. Joint torque of each lower extremity was calculated, and each
      joint peak torque among walking, SS and CS was compared between genders.
      Moreover, correlation between joint torque showed a gender difference and width
      of pelvis normalized by width of shoulder (P/S ratio) was examined. [Results]
      Right external and internal rotation torques during CS were higher in males. Left
      and right-ankle plantar flexion torques were also higher in males during CS,
      while the P/S ratio was larger in females, with a positive correlation between
      P/S ratio and hip external and internal rotation torques. [Conclusion] No gender
      differences were found in joint torque during walking and SS, but only during CS.
      The hip external and internal rotators are necessary for smooth CS in females in
      terms of P/S ratio.

PMID- 29643596
TI  - Effects of interactive metronome training on timing, attention, working memory,
      and processing speed in children with ADHD: a case study of two children.
AB  - [Purpose] The purpose of this study was to present the effects of Interactive
      metronome (IM) on timing for children with Attention-Deficit Hyperactivity
      Disorder (ADHD). [Subjects and Methods] The subjects of the present study were 2
      children diagnosed with ADHD. Pre- and post-intervention tests were completed by
      the researcher using Long Form Assessment (LFA) test of IM and K-WPPSI-IV. The
      subjects were provided with IM for 40 minutes at a time, 2 times per week, for a
      total of 8 weeks. [Results] The timing decreased after IM intervention. The
      subjects showed improvement in attention span after IM intervention. Working
      memory index as well as processing speed index were increased after intervention,
      as shown by the Korean-Wechsler Preschool and Primary Scale of Intelligence-IV (K
      WPPSI-IV). [Conclusion] IM was effective in improving timing, attention, working
      memory and processing speed in children with ADHD.

PMID- 29643597
TI  - Analysis of prejudices and attitudes of students in the department of physical
      therapy against people with disabilities.
AB  - [Purpose] The purpose of this study is to examine prejudices and attitudes of
      students in the department of physical therapy, in order to suggest basic data
      for constructing an effective program to develop a positive attitude toward
      people with disabilities and lower social distance from them. [Subjects and
      Methods] For this study, students in the department of physical therapy
      participate in the survey examining prejudices and attitude towards people with
      disabilities. [Results] First, there were statistically significant differences
      in the prejudice against people with disabilities among student groups divided by
      whether they had contact on a frequent basis currently with those who have
      disabilities. Second, there were statistically significant differences in the
      prejudice against people with disabilities among student groups divided by
      whether they had an experience of being harmed by people with disabilities.
      Third, there was a correlation among prejudices against people with disabilities
      with each other that is articulated in the eighth domain. Finally, as a result of
      regression analysis, the students' attitudes towards people with disabilities
      were explained appropriately by the prejudices about performance of daily tasks
      and NIMBY (Not In My Back Yard) syndrome. [Conclusion] It is crucial to create an
      environment where University students in the department of physical therapy can
      have positive interactions with people with disabilities, to reduce the overall
      prejudices, and specifically, the prejudices about performance of daily tasks and
      about NIMBY syndrome.

PMID- 29643598
TI  - Effects of gait training on sand on improving the walking ability of patients
      with chronic stroke:a randomized controlled trial.
AB  - [Purpose] This study examines how difference in sandy ground between firm ground
      influences the effects of gait training in patients with chronic stroke.
      [Subjects and Methods] A total of 28 patients with chronic stroke were evenly
      divided into experimental and control groups. Initial evaluation of the subjects
      was conducted by Timed Up & Go (TUG) and 6-Minute Walking Test (6MWT). Each
      patient in both groups received daily, 30-minute gait training on sandy ground
      and firm ground, five times each week, for a total of six weeks, after which
      reevaluation was conducted. [Results] In TUG, both groups showed significant
      improvement after the intervention. In 6MWT, only the experimental group achieved
      significantly increased distance after the intervention. However, there was no
      between-group difference. Improvement in dynamic balancing ability depends on
      repeated gait training rather than differences in the ground environment.
      However, gait endurance showed a difference depending on the types of ground,
      regardless of repeated gait training. [Conclusion] This can be attributed to the
      fact that gait training on sand requires use of more diverse muscles. Hence, we
      can confirm the potential of sand as a new material for training ground when
      attempting to improve walking ability, particularly gait endurance, among
      patients with chronic stroke.

PMID- 29643599
TI  - The correlation between diaphragm thickness, diaphragmatic excursion, and
      pulmonary function in patients with chronic stroke.
AB  - [Purpose] This study aimed to investigate the correlation between the diaphragm
      thickness and diaphragm excursion, and pulmonary function in individuals with
      stroke. [Subjects and Methods] One hundred fourteen patients who were clinically
      diagnosed with ischemic or hemorrhagic stroke were included. The diaphragm
      thickness and excursion were assessed using ultrasonography, and the diaphragm
      thickening ratio was standardized using a formula. To analyze pulmonary function,
      we measured the forced vital capacity, forced expiratory volume in one second,
      and peak expiratory flow. [Results] A statistically significant correlation was
      found between the diaphragm thickness, thickness ratio, and diaphragm excursion;
      and the forced vital capacity, forced expiratory volume in one second, and peak
      expiratory flow. [Conclusion] This study demonstrated that there is a
      relationship between respiratory function and diaphragm thickness and diaphragm
      excursion, especially in the paretic side of the diaphragm. Therefore, the role
      of the respiratory muscles of the paretic side is important in rehabilitation
      programs to improve the respiratory function of stroke patients.

PMID- 29643600
TI  - The effect of fluidotherapy on hand dexterity and activities of daily living in
      patients with edema on stroke.
AB  - [Purpose] The purpose of this study was to investigate the effect of
      fluidotherapy on hand's dexterity and activities of daily living for stroke
      patients with upper limb edema. [Subjects and Methods] The objective of the
      present study was to treat 30 stroke patients with a three-week course of
      fluidotherapy to investigate the efficacy of such therapy for reduction of edema.
      For accurate baseline and post-intervention assessment of edema volume, hand
      edema was measured in the morning using a forearm volumeter. [Results] Mean
      edematous volume in the affected side measured 600.53 +/- 29.94 ml prior to
      intervention, significantly decreasing to 533.53 +/- 27.85 ml after three weeks
      of fluidotherapy. To investigate how such reduction may have enhanced the ability
      to perform activities of daily living, Korean Version of Modified Barthel Index
      assessment was performed. The results showed 46.10 +/- 4.27 points at baseline
      and significantly improved to a mean score of 49.96 +/- 4.34 points at the time
      of reassessment. Furthermore, Box and Block Test was performed to investigate
      hand dexterity. Before fluidotherapy, affected patients transferred 21.13 +/-
      3.63 blocks in one minute, increasing to 23.20 +/- 3.42 blocks transferred in one
      minute following three weeks of treatment. Although the number of blocks
      transferred did increase slightly, the difference was not statistically
      significant. [Conclusion] These findings suggest that using fluidotherapy can
      reduce edema, and such a reduction can have a positive effect on activities of
      daily living. Based on our current findings, we hypothesize that long-term
      fluidotherapy treatment may be more effective in reducing edema.

PMID- 29643601
TI  - The effect of group exercise program on the self-efficacy and activities of daily
      living in adults with cerebral palsy.
AB  - [Purpose] This study was carried out to examine the effect of the application of
      group exercise program composed to induce interests and assertive participation
      of adults with cerebral palsy on the self-efficacy and activities of daily
      living, as well as to provide basic clinical data that are effective and
      trustworthy in enhancing the physical and emotional interaction in the future.
      [Subjects and Methods] Those among the 23 adult with cerebral palsy who are the
      subjects of research and able to participate only in the evaluation of
      measurement tools prior to and after the experiment were allocated to the control
      group while only those who can participate in the group exercise program
      implemented over 12 sessions were allocated to the experimental group. For the
      control group, a range of motion of joint exercise and stretching exercise were
      executed on the arms, legs and trunk, while for the experimental group, group
      exercise that is implemented with participation of several subjects
      simultaneously was executed 2 times a week with 40 minutes for each session over
      a period of 6 weeks for the total of 12 sessions. [Results] In both the
      experimental group and the control group, there were statistically significant
      changes in the average scores of self-efficacy and activities of daily living
      after the exercise in comparison to that prior to the exercise. Moreover, there
      were statistically significant differences in self-efficacy and activities of
      daily living in terms of quantity of change prior to and after the exercise
      between the two groups. [Conclusion] Therefore, group exercise program composed
      to induce physical and emotional interaction, and active participation of adults
      with cerebral palsy can be considered as an effective intervention method in
      improving their self-efficacy and activities of daily living.

PMID- 29643602
TI  - Influence of the ultrasound transducer tilt on muscle thickness and echo
      intensity of the rectus femoris muscle of healthy subjects.
AB  - [Purpose] This study aimed to assess the influence of ultrasound (US) transducer
      tilt on muscle thickness and echo intensity of the rectus femoris muscle (RF) in
      healthy subjects. [Subjects and Methods] Fourteen healthy male subjects (20.8 +/-
      0.8 years) participated in this study. Transducer tilt was measured during US,
      with a digital angle gauge. Muscle thickness and echo intensity were measured in
      4 transducer tilt conditions: reference angle; +3 degrees ; +6 degrees ; and +9
      degrees  cranial from the reference angle. [Results] All differences in
      transducer tilt relative to the reference condition were larger than the minimal
      detectable change (MDC) of the reference condition. All differences in muscle
      thickness relative to the reference condition were not larger than the MDC of the
      reference condition. All differences in the echo intensity relative to the
      reference condition, except between the reference and the +3 degrees  condition,
      were larger than the MDC of the reference condition. [Conclusion] Our results
      indicated that an examiner should maintain a precise transducer tilt during
      repeated US measurements to quantify the minimal change in the echo intensity of
      the RF.

PMID- 29643603
TI  - Physical performance of elderly adults in association with thigh tissue
      composition: a cross-sectional study.
AB  - [Purpose] Literature has revealed age-related changes in body regional tissues in
      the form of reduced muscle size and increased adipose tissue. There is also a
      decline in the performance of physical function with aging. The aim of this study
      is to examine the partial and part correlations between physical performance and
      thigh tissue composition among elderly adults. [Subjects and Methods] Twenty-two
      elderly participants enrolled in this cross-sectional study. Mid-thigh CT images
      were used to determine the cross-sectional area of the muscular and adipose
      tissues. Principal component score of physical function was calculated from 5
      performance based physical function tests using principal component analysis.
      Partial and part correlation statistics were used to explore the association
      between physical performance and tissue composition. [Results] There were
      significant, moderate negative partial and part associations between the
      principal component score and cross-sectional area of thigh muscles, quadriceps
      muscle and quadriceps normal density muscle. Significant, moderate positive
      partial and part correlations were found between intramuscular adipose tissue and
      the principal component score. [Conclusion] Elderly adults' performance of
      physical function is associated with regional tissue composition.

PMID- 29643604
TI  - Comparison of efficiency of elastic and non-elastic taping on induced quadriceps
      fatigue by knee extension exercise.
AB  - [Purpose] The purpose of this study is to examine the effects of elastic and non
      elastic taping on induced quadriceps fatigue by knee extension exercise.
      [Subjects and Methods] Thirty healthy females were randomly assigned to an
      elastic tape group (ET, n=10), a non-elastic tape group (NET, n=10), or a no tape
      group (NT, n=10). Taping groups attached taping on quadriceps femoris. Three
      groups are conducted knee extension exercise for 10 times and 3 sets during 10
      minutes. Knee extension peak torque measured before and after knee extension
      exercise. One-way analysis of variance was used to assess the statistical
      significance of knee extension peak torque. [Results] No significant difference
      in changes in maximum muscle strength per unit weight from before to after the
      muscle fatigue exercise was found in the ET, NET, or NT groups (12.1 +/- 4.2,
      11.7 +/- 7.1, and 6.7 +/- 3.4 N/kg, respectively). [Conclusion] Taping
      facilitated muscle performance, but it also increased susceptibility to fatigue
      resulting from greater muscle activation.

PMID- 29643605
TI  - Effect of aquatic versus land based exercise programs on physical performance in
      severely burned patients: a randomized controlled trial.
AB  - [Purpose] To compare the effect of an aquatic-based versus a land-based exercise
      regimen on the physical performance of severely burned patients. [Subjects and
      Methods] Forty patients suffering from severe burn (total body surface area more
      than 30%) were recruited from several outpatient clinics in Greater Cairo. Their
      ages ranged between 20 to 40 years and were randomly assigned into two equal
      groups: group (A), which received an aquatic based exercise program, and group
      (B), which received a land-based exercise program. The exercise program, which
      took place in 12 consecutive weeks, consisted of flexibility, endurance, and
      lower and upper body training. Physical performance was assessed using 30 seconds
      chair stand test, stair climb test, 30 meter fast paced walk test, time up and go
      test, 6-minute walk test and a VO2max evaluation. [Results] Significantly
      increase in the 30 second chair stand, 6-minute walk, 30 meter fast paced walk,
      stair climb, and VO2 max tests and significantly decrease in the time up and go
      test in group A (aquatic based exercise) compared with group B (a land-based
      exercise) at the post treatment. [Conclusion] Twelve-week program of an aquatic
      program yields improvement in both physical performance and VO2 max in patients
      with severe burns.

PMID- 29643606
TI  - Relationship between psychophysiological factors and prognosis for activities of
      daily living in patients with stroke in a recovery rehabilitation unit: a
      preliminary study.
AB  - [Purpose] The objective of the present study was to examine the factors,
      including physical and mental functions, that are associated with the prognosis
      for activities of daily living in patients with stroke in a recovery
      rehabilitation unit. [Subjects and Methods] The subjects were 13 patients with
      stroke who were admitted to the recovery rehabilitation unit of Tokai Memorial
      Hospital between March and October 2014 and followed up for 2 months. Their
      physical and mental functions were evaluated at the time of admission and the
      relationship between these functions and activities of daily living was assessed
      2 months later. [Results] The activities of daily living at 2 months after
      admission showed a significant correlation not only with the severity of motor
      paralysis (R=-0.80) but mental function (R=-0.69) at the time of admission. No
      significant correlation was noted between the severity of motor paralysis and the
      mental function. [Conclusion] It is important to evaluate both mental function
      and severity of motor paralysis immediately after patients' admission to the
      recovery rehabilitation unit. Mental health intervention should be considered in
      the future to effectively improve subsequent activities of daily living.

PMID- 29643607
TI  - Changes in gluteal pressure and center of force during sitting in children with
      cerebral palsy.
AB  - [Purpose] The purpose of this study was to measure gluteal pressure and center of
      force (COF) during sitting in children with cerebral palsy (CP). [Subjects and
      Methods] The participants were five children with CP and five typically
      developing controls. We measured peak gluteal pressure and COF using the TekScan
      system. During the measurements, all children sat on the therapeutic table for 1
      minute without back and foot support. [Results] The peak gluteal pressure and COF
      in children with CP were significantly higher than values in controls.
      [Conclusion] This study suggests that it is important to distribute hip pressure
      evenly and transfer COF in a forward direction during rehabilitation in children
      with CP.

PMID- 29643608
TI  - The immediate effect of FES and TENS on gait parameters in patients after stroke.
AB  - [Purpose] This study was conducted to compare the immediate effects of different
      electrotherapies on the gait parameters for stroke patients. [Subjects and
      Methods] Thirty patients with stroke were randomly assigned either to the
      functional electrical stimulation group or the transcutaneous electrical nerve
      stimulation group, with 15 patients in each group. Each electrotherapy was
      performed for 30 minutes simultaneously with the therapeutic exercise, and the
      changes in the spatial and temporal parameters of gait were measured. [Results]
      After the intervention, a significant, immediate improvement in cadence and speed
      was observed only in the functional electrical stimulation group. [Conclusion]
      Based on this study, functional electrical stimulation that stimulates motor
      nerves of the dorsiflexor muscles on the paretic side is recommended to achieve
      immediate improvement in the gait ability of stroke patients.

PMID- 29643609
TI  - Assessing the adjustability of grasping force using the iWakka in elderly
      individuals.
AB  - [Purpose] To ensure that elderly individuals continue performing their activities
      of daily living, rehabilitation specialists have focused on several intervention
      programs, including programs that help maintain the functionality of digits.
      Grasping motion, including the ability to adjust grip, both spatially and
      temporally, is important for the elderly to continue independent living. The
      iWakka is a device used to measure the adjustability of grasping force and
      developed in Japan in 2012. This study aimed to evaluate the range of error of
      the iWakka, and verify its usefulness for evaluating adjustability of grasping
      force in elderly subjects. [Subjects and Methods] In 36 community-dwelling
      elderly subjects, over 65 years old, two readings of adjustability of grasping
      force, in the dominant and non-dominant hands were obtained using the iWakka, and
      a Bland-Altman analysis of the data was performed. [Results] The results
      demonstrated significant fixed bias in the dominant and non-dominant hands, but
      no significant proportional bias was observed. The limits of agreement were -2.8
      to 4.4 g for dominant hand and -2.6 to 3.9 g for non-dominant hand. [Conclusion]
      Therefore, it is possible to measure the efficacy of interventions and detect
      declines in adjustability of grasping force using iWakka. Interventional programs
      can be designed for daily life based on the grasping force results shown by
      iWakka.

PMID- 29643610
TI  - Effect of the trunk forward bending angle in sitting position on slow vital
      capacity.
AB  - [Purpose] The purpose of this study was to examine whether a trunk forward
      bending angle in sitting position affected slow vital capacity (SVC). [Subjects
      and Methods] The subjects of this study were 18 healthy college students to whom
      the study's methods and purpose were explained and their agreement for
      participation was obtained. Slow vital capacity was measured using spirometry
      (Pony FX, COSMED Inc., Italy), repeatedly at a body bending angle of 0 degrees ,
      15 degrees , and 30 degrees  in the sitting position. [Results] Vital capacity,
      expiratory reserve volume, and inspiratory reserve volume were significantly
      different according to the trunk forward bending angle. There were no
      statistically significant differences in tidal volume and inspiratory capacity.
      [Conclusion] The results demonstrated that the body bending angle of 15 degrees 
      in the sitting position was the most effective angle for increasing lung volume.

PMID- 29643611
TI  - Normative reference values for the two-minute walk test derived by meta-analysis.
AB  - [Purpose] This meta-analysis was undertaken to establish normative reference
      values for the two-minute walk test. [Methods] Three database searches and a hand
      search were conducted. Meta-analysis was used to consolidate two-minute walk test
      data stratified by gender and age group. [Results] Data from four articles was
      consolidated. Normative two-minute walk test distances varied from 150.3 m
      (women, 70 to 79 years) to 217.9 m (men, 20 to 29 tears). [Conclusion] Normative
      reference values derived using meta-analysis should provide a better standard
      than individual studies for interpreting the two-minute walk test performance of
      adults.

PMID- 29643612
TI  - Cognitive behavioural therapy and pain coping skills training for osteoarthritis
      knee pain management: a systematic review.
AB  - [Purpose] To investigate the effectiveness of cognitive-behavioural therapy (CBT)
      and pain coping skills training (PCST) on pain level in adults with
      osteoarthritis of the knee (KOA) in comparison with usual care. [Subjects and
      Methods] Five databases were systematically searched for relevant randomised
      controlled trials (RCTs) according to the selected eligibility criteria
      (inception to June 7, 2016). PEDro scale was used to assess the validity of
      included studies. [Results] Four studies met the inclusion criteria and all
      studies had high methodological quality. The total number of participants was 665
      across the four included studies. All participants had been diagnosed with KOA
      (clinical and radiographic evaluation). The majority of the population were
      female (71.13%). The interventions utilised were: CBT, CBT for insomnia (CBT-I),
      PCST, and PCST combined with behavioral weight management (BWM) in one study and
      with exercise in another study. The outcome measure for pain in KOA was the WOMAC
      scale. Overall, three studies have reported clinical improvement in KOA pain
      perception after 12-month follow-up time point. [Conclusion] This review has
      recognised the need for future studies that have rigorous methodological quality,
      and investigate the effect of mutual CBT and PCST protocols on KOA pain and pain
      related functional and psychological abilities.

PMID- 29643613
TI  - Medical Council of India's amended qualifications for Indian medical teachers:
      Well intended, yet half-hearted.

PMID- 29643614
TI  - Perioperative Communication: Challenges and Opportunities for Anesthesiologists.

PMID- 29643615
TI  - WHO safe surgery checklist: Barriers to universal acceptance.
AB  - Development of the Safe Surgery Checklist is an initiative taken by the World
      Health Organization (WHO) with an aim to reduce the complication rates during the
      surgical process. Despite gross reduction in the infection rate and morbidity
      following adoption of the checklist, many health-care providers are hesitant in
      implementing it in their everyday practice. In this article, we would like to
      highlight the hurdles in adoption of the WHO Surgical Checklist and measures that
      can be taken to overcome them.

PMID- 29643616
TI  - Labor analgesia in parturients of fetal growth restriction having raised
      umbilical Doppler vascular indices.
AB  - Background and Aims: Fetuses with abnormal umbilical blood flow are at a higher
      risk of adverse perinatal outcome than those with normal flow. Epidural analgesia
      (EA) has shown to decrease villous vascular resistance in preeclamptic women
      during labor. The present study evaluates the effects of epidural ropivacaine and
      intramuscular (IM) tramadol on Doppler blood flow in parturients with fetal
      growth restriction and raised umbilical artery (UmA) blood flow. Material and
      Methods: In this prospective nonrandomized comparative study, 36 term parturients
      with sonographic evidence of UmA systolic-diastolic (S-D) ratio >=3 were
      enrolled. Parturients received either continuous epidural ropivacaine 0.2% or 1
      mg/kg IM tramadol 4-6 hourly. Doppler flow parameters of UmA and bilateral
      uterine arteries (UtAs) were measured at 0, 1, and 6 h of labor analgesia.
      Doppler indices change with time during labor analgesia was assessed as the
      primary outcome. Change of Doppler indices of UtAs, Apgar score, and cord blood
      gases was considered as secondary measures. Results: Data from thirty laboring
      women who completed the study were analyzed. The pulsatility index, resistance
      index, and S-D ratio in UmA and right UtA reduced significantly with continuous
      epidural infusion during first 6 h of labor. However, these values increased or
      unchanged with tramadol administration. Better neonatal pH and base deficit (P =
      0.039) were observed with EA. Conclusions: Continuous epidural ropivacaine causes
      improved fetoplacental circulation in parturients with growth-restricted fetuses
      having raised Doppler indices during labor analgesia. We also found better
      neonatal outcome with continuous infusion of epidural ropivacaine as compared to
      IM tramadol.

PMID- 29643617
TI  - Comparison of ropivacaine (0.2%) with or without clonidine 1 MUg/kg for epidural
      labor analgesia: A randomized controlled study.
AB  - Background and Aims: The aim is to determine the effect of addition of clonidine
      to ropivacaine for epidural labor analgesia with regard to onset of analgesia,
      duration of analgesia, neonatal outcome, and quality of analgesia. Material and
      Methods: A total of 60 term parturients of the American Society of
      Anesthesiologists Grade I and II with uncomplicated pregnancy, vertex
      presentation, posted for on-demand epidural labor analgesia after informed
      consent were divided in two groups. Group R (n = 30) patients received 10 ml
      solution comprising 0.2% ropivacaine. Group RC (n = 30) patients received a total
      of 10 ml of 0.2% ropivacaine and clonidine 1 MUg/kg. Characteristics of the
      block, onset and duration of analgesia, and total analgesic requirements were
      noted. Pain and overall satisfaction scores were assessed with a 10-point visual
      analog scale. Mode of delivery and neonatal APGAR scores were recorded. Results:
      Maternal demographic characteristics were comparable between the groups. Addition
      of clonidine to ropivacaine shortened the onset and prolonged the duration of
      analgesia with decrease in ropivacaine requirement in Group RC. There was a
      significant difference between the two groups regarding visual analog score and
      quality of analgesia, which was better in Group RC. There were no significant
      differences between the two groups regarding motor block, hemodynamic parameters,
      and neonatal outcomes. Conclusion: We conclude that clonidine in low doses is a
      useful adjuvant to local anesthetics for epidural labor analgesia and a good
      alternative to opioids.

PMID- 29643618
TI  - A randomized clinical trial of intrathecal magnesium sulfate versus midazolam
      with epidural administration of 0.75% ropivacaine for patients with preeclampsia
      scheduled for elective cesarean section.
AB  - Background and Aims: Magnesium sulfate and midazolam have been used as adjuvants
      to local anesthetics via intrathecal and epidural routes to augment the quality
      of block and prolong postoperative analgesia. This study compares addition of
      intrathecal magnesium sulfate versus intrathecal midazolam to epidurally
      administered isobaric ropivacaine as a part of combined spinal epidural technique
      in pre-eclamptic parturients undergoing elective cesarean section. Material and
      Methods: After institutional ethics committee approval and written informed
      consent, 50 pre-eclamptic parturients were randomly allocated to one of the two
      groups of 25 each to either receive intrathecal magnesium sulfate (50 mg) or
      intrathecal midazolam (1 mg) in combination with epidural ropivacaine (0.75%; 14
      16 ml). The onset and duration of sensory and motor blockade, duration of
      postoperative analgesia, postoperative visual analogue scores for pain, and
      perioperative side effects were noted. Data were analyzed statistically using
      Graphpad.com software. Results: Onset times to sensory and motor blockade were
      faster in midazolam than in magnesium group (P < 0.01). Duration of sensory and
      motor blockade, and time to first request of analgesia were significantly longer
      in the magnesium group compared to the midazolam group (P < 0.01). The fetal
      outcomes according to APGAR scores were comparable in both the groups, the median
      APGAR score at 1 minute was 8 and at 5 minutes was 10 in both the groups.
      Conclusion: Intrathecal magnesium with epidural ropivacaine significantly
      prolonged postoperative analgesia compared to intrathecal midazolam without any
      complications. Perioperative hemodynamics were comparable in both groups.

PMID- 29643619
TI  - Comparison of continuous epidural infusion of 0.125% ropivacaine with 1 MUg/ml
      fentanyl versus 0.125% bupivacaine with 1 MUg/ml fentanyl for postoperative
      analgesia in major abdominal surgery.
AB  - Background and Aim: The present study was carried out to compare the efficacy of
      continuous epidural infusion of two amide local anesthetics, ropivacaine and
      bupivacaine with fentanyl for postoperative analgesia in major abdominal
      surgeries. Material and Methods: A total of 60 patients scheduled for major
      abdominal surgery were randomized into two study Groups B and R with thirty
      patients in each group. All patients were administered general anesthesia after
      placing epidural catheter. Patients received continuous epidural infusion of
      either 0.25% bupivacaine with 1 ug/ml fentanyl (Group B) or of 0.25% ropivacaine
      with 1 ug/ml fentanyl (Group R) at the rate 6 ml/h intraoperatively.
      Postoperatively, they received 0.125% bupivacaine with 1 ug/ml fentanyl (Group B)
      or 0.125% ropivacaine with 1 ug/ml fentanyl (Group R) at the rate 6 ml/h.
      Hemodynamic parameters, visual analog scale (VAS), level of sensory block, and
      degree of motor block (based on Bromage scale) were monitored for 24 h
      postoperatively. Results: Hemodynamic parameters and VAS scores were comparable
      in the two groups. The level of sensory block was higher in bupivacaine group.
      There were more patients with higher Bromage score in the (23.3%) bupivacaine
      group than in (6.7%) ropivacaine group though the difference was not
      statistically significant. Conclusion: Both ropivacaine and bupivacaine in the
      concentration of 0.125% with fentanyl 1 ug/ml are equally safe, with minimal
      motor block and are effective in providing postoperative analgesia.

PMID- 29643620
TI  - Opioid-free anesthesia for breast cancer surgery: An observational study.
AB  - Background and Aims: Opioids are associated with postoperative nausea, vomiting,
      drowsiness, and increased analgesic requirement. A nonopioid anesthesia technique
      may reduce morbidity, enable day care surgery, and possibly decrease tumor
      recurrence. We compared opioid-free, nerve block-based anesthesia with opioid
      based general anesthesia for breast cancer surgery in a prospective cohort study.
      Material and Methods: Twenty four adult American Society of Anesthesiologists
      grade I-III patients posted for modified radical mastectomy (MRM) with axillary
      dissection were induced with propofol and maintained on isoflurane (0.8-1.0
      minimum alveolar concentration) through i-gel on spontaneous ventilation and
      administered ultrasound-guided PECS 1 and 2 blocks (0.1% lignocaine + 0.25%
      bupivacaine + 1 mcg/kg dexmedetomidine, 30 ml). Postoperative nausea, pain
      scores, nonopioid analgesic requirement over 24 h, stay in the recovery room, and
      satisfaction of surgeon and patient were studied. Twenty-four patients who
      underwent MRM and axillary dissection without a nerve block under routine opioid
      anesthesia with controlled ventilation were the controls. Results: MRM and
      axillary dissection under the nonopioid technique was adequate in all patients.
      Time in the recovery room, postoperative nausea, analgesic requirement, and
      visual analog scale scores were all significantly less in the nonopioid group.
      Surgeon and patient were satisfied with good patient quality of life on day 7.
      Conclusion: Nonopioid nerve block technique is adequate and safe for MRM with
      axillary clearance. Compared to conventional technique, it offers lesser
      morbidity and may allow for earlier discharge. Larger studies are needed to
      assess the long-term impact on chronic pain and tumor recurrence by nonopioid
      techniques.

PMID- 29643621
TI  - Evaluation of dexmedetomidine and fentanyl as additives to ropivacaine for
      epidural anesthesia and postoperative analgesia.
AB  - Background and Aims: The synergism between epidural local anesthetic agent and
      opioids is well established, but evidence for the combination of local anesthetic
      agent with dexmedetomidine in epidurals is limited. This study evaluates the
      clinical efficacy of dexmedetomidine versus fentanyl as an additive to
      ropivacaine for epidural anesthesia. Material and Methods: Patients undergoing
      infraumbilical surgeries were divided randomly into three groups - Group R (n =
      25): received 18 ml of 0.5% ropivacaine for epidural anesthesia and 10 ml of 0.1%
      ropivacaine boluses for postoperative analgesia; Group RF (n = 25): received 18
      ml of 0.5% ropivacaine with 20 MUg fentanyl for epidural anesthesia and 10 ml of
      0.1% ropivacaine with 10 MUg fentanyl boluses for postoperative analgesia; and
      Group RD (n = 25): received 18 ml of 0.5% ropivacaine with 10 MUg dexmedetomidine
      for epidural anesthesia and 10 ml of 0.1% ropivacaine with 5 MUg dexmedetomidine
      boluses for postoperative analgesia. Results: The mean time for onset of sensory
      block, in minutes, was 18.6 +/- 4.4 in R Group, 12.8 +/- 1.8 in RF Group and 10.8
      +/- 2.7 in RD Group (P < 0.001). There was a statistically significant difference
      with regard to degree of motor block, with RD Group faring better than RF Group
      and R Group. The mean time to rescue analgesia, in minutes, was 139.8 +/- 21.4 in
      Group R, 243 +/- 29.7 in Group RF, and 312.4 +/- 30.2 in Group RD (P < 0.001).
      Incidence of hypotension at 10 min was 4% and 48% in RF and RD Groups,
      respectively (P < 0.001). Conclusions: Epidural anesthesia achieved with 10 MUg
      dexmedetomidine as an additive to 0.5% ropivacaine is more effective with respect
      to duration and intensity of analgesia when compared to 0.5% ropivacaine alone or
      addition of 20 MUg fentanyl to 0.5% ropivacaine.

PMID- 29643622
TI  - Effect of intravenous dexmedetomidine administered as bolus or as bolus-plus
      infusion on subarachnoid anesthesia with hyperbaric bupivacaine.
AB  - Background: Subarachnoid anesthesia is a widely practiced regional anesthetic for
      infraumbilical surgeries. Intravenous dexmedetomidine is known to prolong both
      sensory and motor blockade when administered along with subarachnoid anesthesia.
      Material and Methods: Seventy-five patients scheduled to undergo elective
      infraumbilical surgeries under subarachnoid anesthesia were randomly allocated to
      one of the three groups. Group B received intravenous saline over 10 min followed
      by 12.5 mg intrathecal bupivacaine and then intravenous saline over 60 min. Group
      bupivacaine + dexmedetomidine bolus (BDexB) received intravenous dexmedetomidine
      (1 MUg/kg) over 10 min followed by 12.5 mg intrathecal bupivacaine and then
      intravenous saline over 60 min. Group bupivacaine + dexmedetomidine bolus-plus
      infusion (BDexBI) received intravenous dexmedetomidine (0.5 MUg/kg) over 10 min
      followed by 12.5 mg intrathecal bupivacaine and then intravenous dexmedetomidine
      (0.5 MUg/kg) over 60 min. Onset of analgesia (at T10), complete motor block
      (Bromage score 3), and highest level of analgesia were noted. Sensory and motor
      levels were checked periodically till sensory recovery (at S2-S4) and complete
      motor recovery (Bromage score 0). Ramsay sedation score and incidence of
      bradycardia/hypotension were noted. Results: Sensory recovery was significantly
      longer in Group BDexB (303 min) and Group BdexBI (288 min) as compared to Group B
      (219.6 min). Motor recovery was also significantly prolonged in Group BDexB
      (321.6 min) and Group BDexBI (302.4 min) as compared to Group B (233.4 min).
      Patients receiving dexmedetomidine were sedated but were easily arousable.
      Conclusion: Intravenous dexmedetomidine given as bolus or bolus-plus-infusion
      with intrathecal hyperbaric bupivacaine prolongs both sensory and motor blockade.

PMID- 29643623
TI  - Effect of dexmedetomidine infusion on hemodynamic responses in microsurgery of
      larynx.
AB  - Background and Aims: Microlaryngeal surgery is a frequently performed ear, nose,
      and throat procedure used to diagnose and treat laryngeal disorders. Suspension
      laryngoscopy causes prolonged stimulation of the deep pressure receptors of the
      larynx leading to adverse circulatory responses and consequently cardiac
      complications. In this study, dexmedetomidine infusion was used to assess its
      effectiveness for attenuation of this hemodynamic stress response. Material and
      Methods: Sixty patients undergoing elective microlaryngeal surgery randomly
      received either dexmedetomidine 1 MUg/kg over 10 min followed by continuous
      infusion of 0.5 MUg/kg (Group D) or normal saline infusion at the same rate
      (Group P) till the end of surgery. Anesthesia in all patients was induced with
      propofol, succinylcholine to facilitate endotracheal intubation after
      premedication with fentanyl 2 MUg/kg and glycopyrrolate. Intraoperative, vital
      parameters were maintained within 20% of baseline with rescue analgesic fentanyl
      1 MUg/kg and subsequently with propofol boluses up to 1 mg/kg. The percentage of
      patients and the total amount of intraoperative fentanyl and propofol required in
      each group were recorded. Sedation score at 10 minutes postextubation was
      assessed by Ramsay sedation score. Results: Intraoperative heart rate and mean
      arterial pressure in Group D were lower than the baseline values and the
      corresponding values in Group P (P > 0.05). The percentage of patients requiring
      rescue fentanyl and propofol was higher in Group P than Group D (36.6% and 30%
      vs. 6.6% and 3.3% P = 0.01). Recovery scores were better in dexmedetomidine
      group. Conclusion: Dexmedetomidine infusion attenuates the hemodynamic stress
      response during laryngoscopy, intubation, and microlaryngeal surgery and is
      associated better recovery profile.

PMID- 29643624
TI  - Effectiveness of Proseal laryngeal mask airway and laryngeal tube suction in
      elective non-laparoscopic surgeries of up to ninety minutes duration: A
      prospective, randomized study.
AB  - Background and Aims: Proseal laryngeal mask airway (LMA) and laryngeal tube
      suction (LTS) are both supraglottic devices with an esophageal suction port. In
      the present prospective, randomized study, the effectiveness of airway seal,
      hemodynamic variables, ability to pass orogastric tube, and postoperative
      complications with the two devices were evaluated. Material and Methods: This was
      a prospective, randomized, single-blind study conducted in a hospital-based
      setting. Sixty patients (American Society of Anesthesiologists Grade I and II)
      undergoing elective general surgery were randomly allocated to Group A (Proseal
      LMA) or Group B (LTS), and airway seal pressure (primary outcome), peak pressure,
      hemodynamic parameters (blood pressure, pulse rate and pulse oximetry) during and
      5 min after insertion, insertion time, ease of insertion, and postoperative
      complications (sore throat and hoarseness of voice for a period of 24 hours)
      (secondary outcomes) were noted. The quantitative data was summarized as mean and
      standard deviation, and analyzed using Student's t-test. All the qualitative data
      were summarized as proportions and analyzed using Chi-square test. The levels of
      significance and alpha-error were kept 95% and 5%, respectively, for all
      statistical analyses. P <= 0.05 was considered significant (S). Results: Proseal
      LMA had shorter insertion time (16.4 +/- 5.6 vs. 20.0 +/- 3.9 s), higher seal
      pressure (27.6 +/- 4.6 vs. 24.1 +/- 5.6 cm of H2O), lesser peak pressure (16.3 +/
      2.3 vs. 18.5 +/- 3.9 cm of H2O), higher success rate of orogastric tube passage
      (86.7 vs. 76.7%), and lesser postoperative sore throat (3.3 vs. 10%).
      Conclusions: Both Proseal LMA and LTS were acceptable alternatives for airway
      management in elective surgeries with controlled ventilation, but the quality of
      ventilation was found to be significantly better with Proseal LMA (in terms of
      higher seal pressure, lesser peak pressure, lesser insertion time, and lesser
      complications).

PMID- 29643625
TI  - Formulation of a multivariate predictive model for difficult intubation: A double
      blinded prospective study.
AB  - Background and Aims: Various models were devised for prediction of difficult
      intubation but have low positive predictive value, sensitivity and specificity.
      We aimed to predict difficult intubation from various airway predictive indices,
      in isolation and combination, and to formulate a multivariate model that can aid
      in accurate prediction of difficult intubation. Material and Methods: A
      prospective double blinded study was conducted on 500 adult patients scheduled
      for elective surgery under general anaesthesia. Preoperatively, they were
      assessed for airway screening tests. After standardized induction of anaesthesia,
      laryngoscopic view was classified according to the Modified Cormack and Lehane
      (MCL) classification. Variables' association with intubation findings was
      evaluated using Chi-square statistic. Stepwise logistic regression identified the
      multivariate independent predictors of difficult intubation and combinations were
      made using forward selection process. 8 models were formulated and a receiver
      operating characteristic (ROC) curve worked out for them. Sensitivity and
      specificity analysis validated the final model. Results: Age, sex, weight, BMI,
      snoring, obstructive sleep apnea (OSA), diabetes, hypertension, upper lip bite
      test (ULBT), Mallampati grade (MPS), thyromental distance (TMD), sternomental
      distance (SMD), neck movements (NM), neck circumference (NC) and inter-incisor
      gap (IIG) had significant correlation with difficult intubation. Based upon
      sensitivity and specificity analysis, model comprising of MPS, NM, NC and SMD was
      found to be most accurate. It had highest sensitivity 80%, specificity 87% and
      area under curve 0.90, thus validating the model. Conclusions: Our study found
      that a combination of MPS, SMD, NM and NC permits reliable, accurate and quick
      preoperative prediction of difficult intubation.

PMID- 29643626
TI  - Ratio of height-to-thyromental distance and ratio of height-to-sternomental
      distance as predictors of laryngoscopic grade in children.
AB  - Background and Aims: Failure to secure the airway is an important cause of
      morbidity and mortality in children. Children are often uncooperative for routine
      examination and pose problems for obtaining external measurements. We aimed to
      evaluate ratio of height-to-thyromental distance (RHTMD) and ratio of height-to
      sternomental distance (RHSMD) as predictors of laryngoscopic grade in children
      aged 1-12 years. Material and Methods: This study was an observational study
      conducted in children aged between 1 and 12 years scheduled for elective surgery
      under general anesthesia. Children unable to stand, having limited mouth
      opening/neck mobility, cleft palate or with midline neck masses were excluded.
      Weight, height, and thyromental and sternomental distances were measured
      preoperatively. Following induction of anesthesia and full-muscle relaxation,
      laryngoscopy was performed and Cormack-Lehane view with Cook's modification was
      noted. Receiver operating characteristic (ROC) curve analysis using RHTMD and
      RHSMD was performed for predicting poor laryngoscopic view. Results: A total of
      138 children with mean age of 6.6 +/- 3.4, RHTMD of 17.7 +/- 2.1, and RHSMD of
      10.0 +/- 1.0 were included. No Grade 3 or 4 laryngoscopic views were obtained.
      ROC curve analysis was done for predicting 2b view (restricted), incidence of
      which was 10.1%. RHTMD was a better predictor of 2b laryngoscopic view with an
      area under curve (AUC) of 0.792 compared to RHSMD (AUC = 0.463). Conclusions: In
      children aged 1-12 years, RHTMD is a better predictor of restricted view compared
      to RHSMD.

PMID- 29643627
TI  - Predicting endotracheal tube size from length: Evaluation of the Broselow tape in
      Indian children.
AB  - Background and Aims: Several formulae are available to estimate endotracheal tube
      (ETT) size in children. This study was designed to compare the ETT estimated by
      the Broselow tape (BT) with age-based estimation of ETT size and to identify the
      most accurate formula for the prediction of uncuffed ETT size in Indian children.
      Material and Methods: Pediatric patients aged 1 month-6.5 years undergoing
      emergency or elective surgery under general anesthesia requiring endotracheal
      intubation with uncuffed ETT were included in this study. The ETT size was
      selected based on the age formula (Penlington formula). The ETT used was deemed
      to be of correct fit based on the delivery of adequate tidal volume and presence
      of minimal leak at 20 cm H2O. The actual ETT used was compared with that
      predicted by age, length of the child, BT, and fifth fingernail width of the
      child using Pearson's correlation. Results: In children aged <6 months, the ETT
      used was found to correlate with length (r = 0.286, P = 0.044) and finger nail
      width (r = 0.542, P < 0.001) of the children. In children >6 months, the ETT used
      correlated with that predicted from age, BT, length, and fingernail width of the
      children. In our study, BT has an overall correct predictability rate of 50.3%
      whereas the age-based formula has a correct prediction rate of 59.8% and length
      based formula is 48.7% accurate. Conclusion: Length of the child has a good
      correlation with size of the ETT to be used in Indian children across all age
      groups. BT is an effective tool to predict ETT size in children >6 months.

PMID- 29643628
TI  - Pediatric critical incidents reported over 15 years at a tertiary care teaching
      hospital of a developing country.
AB  - Background and Aims: The role of critical incident (CI) reporting is well
      established in improving patient safety but only a limited number of available
      reports relate to pediatric incidents. Our aim was to analyze the reported CIs
      specific to pediatric patients in our database and to reevaluate the value of
      this program in addressing issues in pediatric anesthesia practice. Material and
      Methods: Incidents related to pediatric population from neonatal period till the
      age of 12 years were selected. A review of all CI records collected between
      January 1998 and December 2012, in the Department of Anaesthesiology of Aga Khan
      University hospital was done. This was retrospective form review. The Department
      has a structured CI form in use since 1998 which is intermittently evaluated and
      modified if needed. Results: A total of 451 pediatric CIs were included. Thirty
      four percent of the incidents were reported in infants. Ninety-six percent of the
      reported incidents took place during elective surgery and 4% during emergency
      surgery. Equipment-related events (n = 114), respiratory events (n = 112), and
      drug events (n = 110) were equally distributed (25.6%, 25.3%, and 24.7%). Human
      factors accounted for 74% of reports followed by, equipment failure (10%) and
      patient factors (8%). Only 5% of the incidents were system errors. Failure to
      check (equipment/drugs/doses) was the most common cause for human factors. Poor
      outcome was seen in 7% of cases. Conclusion: Medication and equipment are the
      clinical areas that need to be looked at more closely. We also recommend quality
      improvement projects in both these areas as well as training of residents and
      staff in managing airway-related problems in pediatric patients.

PMID- 29643629
TI  - Intraoperative neurophysiological monitoring team's communique with anesthesia
      professionals.
AB  - Background and Aims: Intraoperative neurophysiological monitoring (IONM) is the
      standard of care during many spinal, vascular, and intracranial surgeries. High
      quality perioperative care requires the communication and cooperation of several
      multidisciplinary teams. One of these multidisciplinary services is
      intraoperative neuromonitoring (IONM), while other teams represent anesthesia and
      surgery. Few studies have investigated the IONM team's objective communication
      with anesthesia providers. We conducted a retrospective review of IONM-related
      quality assurance data to identify how changes in the evoked potentials observed
      during the surgery were communicated within our IONM-anesthesia team and
      determined the resulting qualitative outcomes. Material and Methods: Quality
      assurance records of 3,112 patients who underwent surgical procedures with IONM
      (from 2010 to 2015) were reviewed. We examined communications regarding
      perioperative evoked potential or electroencephalography (EEG) fluctuations that
      prompted neurophysiologists to alert/notify the anesthesia team to consider
      alteration of anesthetic depth/drug regimen or patient positioning and analyzed
      the outcomes of these interventions. Results: Of the total of 1280 (41.13%)
      communications issued, there were 347 notifications and 11 alerts made by the
      neurophysiologist to the anesthesia team for various types of neuro/orthopedic
      surgeries. Prompt communication led to resolution of 90% of alerts and 80% of
      notifications after corrective measures were executed by the anesthesiologists.
      Notifications mainly related to limb malpositioning and extravasation of
      intravenous fluid. Conclusion: Based on our institutions' protocol and algorithm
      for intervention during IONM-supported surgeries, our findings of resolution in
      alerts and notifications indicate that successful communications between the two
      teams could potentially lead to improved anesthetic care and patient safety.

PMID- 29643630
TI  - Comparison of pretreatment with dexmedetomidine with midazolam for prevention of
      etomidate-induced myoclonus and attenuation of stress response at intubation: A
      randomized controlled study.
AB  - Background and Aims: Myoclonus is a common problem during induction of anesthesia
      with etomidate. A variety of drugs have been used to decrease the incidence of
      myoclonus. In this study we compared the effects of dexmedetomidine and midazolam
      pretreatment on the incidence of etomidate induced myoclonus. We also studied the
      effects of these drugs on attenuation of stress response at laryngoscopy and
      intubation on induction with etomidate. Material and Methods: Eighty adult
      patients (18 to 60 years age) of either sex, American Society of Anestheiologists
      physical status I and II undergoing elective general surgeries under general
      anesthesia were randomly allocated into two groups. Group D patients received
      Inj. Dexmedetomidine (0.5 MUg/Kg) and Group M received Inj. Midazolam (0.015
      mg/Kg) in 10 ml saline over ten minutes. Myoclonus was graded after intravenous
      administration of etomidate (0.3mg/Kg) and hemodynamic response to laryngoscopy
      and intubation were observed at various time intervals. Analysis of statistical
      data was done using Statistical Package for Social Sciences (SPSS) version 21.0.
      Quantitative variables were compared using Independent T Test/Mann Whitney test
      (for non-parametric data). Qualitative variables were compared using Chi-Square
      test/Fisher's Exact Test. A P value of < 0.05 was considered statistically
      significant. Results: In Group D, 22 out of 40 (55%) patients did not have any
      myoclonus during induction with etomidate, and none of the patients had grade 3
      (severe) myoclonus. In Group M, 19 out of 40 patients (47.5%) had grade 2
      (moderate) and 6 patients (15%) had grade 3 myoclonus. Stress response due to
      intubation was more effectively suppressed by dexmedetomidine as compared to
      midazolam. Conclusion: Incidence of myoclonus among patients who underwent pre
      treatment with dexmedetomidine was significantly lesser than those who underwent
      pre-treatment with midazolam. Greater degree of attenuation of stress response in
      the dexmedetomidine group was observed as compared to midazolam group.

PMID- 29643631
TI  - Safety of the medical gas pipeline system.
AB  - Medical gases are nowadays being used for a number of diverse clinical
      applications and its piped delivery is a landmark achievement in the field of
      patient care. Patient safety is of paramount importance in the design,
      installation, commissioning, and operation of medical gas pipeline systems
      (MGPS). The system has to be operational round the clock, with practically zero
      downtime and its failure can be fatal if not restored at the earliest. There is a
      lack of awareness among the clinicians regarding the medico-legal aspect involved
      with the MGPS. It is a highly technical field; hence, an in-depth knowledge is a
      must to ensure safety with the system.

PMID- 29643632
TI  - Venous gas embolism in operative hysteroscopy: A devastating complication in a
      relatively simple surgery.
AB  - Venous air embolism can be a catastrophic iatrogenic complication during
      operative hysteroscopy and makes this simple surgical procedure very risky,
      especially with the lack of knowledge about its prevention, presentation, and
      immediate management. Three out of 13 hysteroscopic myoma resections at our
      center had venous gas embolism (VGE). The prevention, diagnosis, and management
      of VGE are described in this report of three cases.

PMID- 29643633
TI  - Anesthetic efficacy of 4% articaine and 2% lignocaine in achieving palatal
      anesthesia following a single buccal infiltration during periodontal therapy: A
      randomized double-blind split-mouth study.
AB  - Background: The aim of this randomized split-mouth double-blind study was to
      evaluate whether 4% articaine hydrochloride with 1:100,000 epinephrine
      administered as a single buccal infiltration in the maxillary posterior sextant
      can provide palatal anesthesia when compared with 2% lignocaine with 1:100,000
      epinephrine during scaling and root planing and access flap surgery (AFS).
      Material and Methods: A total of 40 patients with chronic generalized
      periodontitis requiring periodontal therapy in the maxillary posterior sextants
      were recruited in this study. About 4% articaine and 2% lignocaine were
      administered as buccal infiltration in a split-mouth design randomly. The pain
      scores in the palatal aspect were recorded during scaling and root planing and
      open flap debridement using Heft-Parker visual analog scale. The onset of
      anesthesia was also recorded and compared. Results: The success rate for
      maxillary buccal infiltration to induce palatal anesthesia using articaine was
      90% during scaling and root planing and 82.5% during AFS and for lignocaine
      solution was 20% and 15%, respectively. The difference between the two agents was
      statistically significant (P < 0.05). The onset of anesthesia between articaine
      and lignocaine was also found to be statistically significant (P < 0.05).
      Conclusion: In this study, we observed that the efficacy of 4% articaine was
      superior to 2% lignocaine to induce palatal anesthesia following maxillary buccal
      infiltration in maxillary posterior sextants.

PMID- 29643634
TI  - Tanezumab: Therapy targeting nerve growth factor in pain pathogenesis.
AB  - In recent years, nerve growth factor (NGF) and the NGF receptor have become
      potential therapeutic targets in the treatment of acute and chronic pain states.
      NGF is a neurotrophin involved in regulating the function of sensory and
      sympathetic neurons during development. Numerous pain states have been linked to
      elevated levels of NGF and its role in increasing the perception of pain.
      Tanezumab, a recombinant humanized monoclonal antibody (IgG), was developed to
      target NGF, binding both circulating and local tissue NGF preventing interaction
      with the tropomyosin-related kinase-A and p75 receptors. Recent clinical studies
      with tanezumab in different patient populations to date, including
      osteoarthritis, low back pain, and diabetic peripheral neuropathy, demonstrate
      efficacy with few side effects, including transient arthralgias, paresthesias,
      hypoesthesia, and rarely, osteonecrosis. Anti-NGF antibodies are a novel therapy
      in pain management and have shown promise in the treatment of certain pain
      conditions, which at present are poorly treated. Tanezumab offers an exciting new
      class of analgesics that has the potential to change the treatment of pain.

PMID- 29643635
TI  - Regional anesthesia is safe and effective for lower limb orthopedic surgery in
      patient with renal tubular acidosis and hypokalemia.
AB  - Renal tubular acidosis (RTA) with hypokalemia may precipitate acute respiratory
      failure and potentially fatal arrhythmias like ventricular fibrillation. Though
      there are random reports of respiratory failure needing mechanical ventilation
      and sudden death in patients with RTA and hypokalemia, the anesthetic management
      of these patients has not been clearly elucidated. Acidosis and hypokalemia have
      significant interactions with both general and local anesthetics and alter their
      effect substantially. Proper preoperative planning and optimization are required
      for the safe conduct of anesthesia in this subset of patients. We describe a case
      of distal RTA, hypokalemia, and metabolic bone disease in whom central neuraxial
      anesthesia was effectively used for lower limb orthopedic surgery with no
      complications.

PMID- 29643636
TI  - Atypical presentation of posterior reversible encephalopathy syndrome: Two cases.
AB  - Posterior reversible encephalopathy syndrome (PRES) is a clinico
      neuroradiological entity, first described in 1996. It is commonly associated with
      systemic hypertension, intake of immunosuppressant drugs, sepsis and eclampsia
      and preeclampsia. Headache, alteration in consciousness, visual disturbances and
      seizures are common manifestations of PRES. Signs of pyramidal tract involvement
      and motor dysfunction are uncommon clinical findings. However, clinical
      presentation is not diagnostic. On neuroimaging, lesions are characteristically
      found in parieto occipital region of the brain due to vasogenic edema. We report
      two cases of PRES with atypical clinical presentation-one which was suggestive of
      neurocysticercosis and the other in which agitation and opisthotonic posture were
      predominant features.

PMID- 29643637
TI  - Neostigmine-induced coronary spasm: Beware of Kounis syndrome.

PMID- 29643638
TI  - Anesthetic management of excision of laryngocele-role of transtracheal jet
      ventilation.

PMID- 29643639
TI  - Awake caudal anesthesia for anoplasty in a preterm newborn with complex cyanotic
      congenital heart disease.

PMID- 29643640
TI  - An easy and feasible way of confirming correct placement of ventriculoatrial
      shunt intraoperatively.

PMID- 29643641
TI  - Pierre robin sequence with cervicothoracic kyphoscoliosis: An anesthetic
      challenge.

PMID- 29643642
TI  - Needle tip and peripheral nerve blocks.

PMID- 29643643
TI  - Ultrasound-guided internal jugular vein cannulation: Can an artery be missed?

PMID- 29643644
TI  - A Case of Gorhams Syndrome: An anesthetic challenge.

PMID- 29643645
TI  - "Look alike" packaging: Do we need a wake-up call?

PMID- 29643646
TI  - Leak in anesthesia workstation: An unusual cause.

PMID- 29643647
TI  - Propofol infusion in an infant with glucose-6-phosphate dehydrogenase deficiency.

PMID- 29643648
TI  - Acute compartment syndrome in the postoperative period in an alcoholic patient
      with multiple injuries.

PMID- 29643649
TI  - Water contamination of the central air supply: Out of sight, out of mind!

PMID- 29643650
TI  - Minocycline: The second important antimicrobial in multidrug-resistant
      Acinetobacter baumanii infections.

PMID- 29643651
TI  - Pilot Study of an Open-source Image Analysis Software for Automated Screening of
      Conventional Cervical Smears.
AB  - Introduction: The Pap stained cervical smear is a screening tool for cervical
      cancer. Commercial systems are used for automated screening of liquid based
      cervical smears. However, there is no image analysis software used for
      conventional cervical smears. The aim of this study was to develop and test the
      diagnostic accuracy of a software for analysis of conventional smears. Materials
      and Methods: The software was developed using Python programming language and
      open source libraries. It was standardized with images from Bethesda
      Interobserver Reproducibility Project. One hundred and thirty images from smears
      which were reported Negative for Intraepithelial Lesion or Malignancy (NILM), and
      45 images where some abnormality has been reported, were collected from the
      archives of the hospital. The software was then tested on the images. Results:
      The software was able to segregate images based on overall nuclear: cytoplasmic
      ratio, coefficient of variation (CV) in nuclear size, nuclear membrane
      irregularity, and clustering. 68.88% of abnormal images were flagged by the
      software, as well as 19.23% of NILM images. The major difficulties faced were
      segmentation of overlapping cell clusters and separation of neutrophils.
      Conclusion: The software shows potential as a screening tool for conventional
      cervical smears; however, further refinement in technique is required.

PMID- 29643652
TI  - Utility of Cytokeratin7 Immunocytochemistry in the Cytopathological Diagnosis of
      Fibrolamellar Hepatocellular Carcinoma.
AB  - Objective: To distinguish fibrolamellar hepatocellular carcinoma (FL-HCC) variant
      from the conventional hepatocellular carcinoma (HCC) by cytology,
      immunocytochemistry, and morphometry. Study Design: Retrospective detailed
      cytomorphological, immunocytochemical, and morphometric analysis was performed in
      6 cases of FL-HCC reported on fine needle aspiration. Cell block
      immunocytochemistry (CB-ICC) for CK7 and CD68 was performed in four cases.
      Morphometry was carried out with Cell A software. Area of the cell, nucleus and
      nucleolus was measured in 50 nuclei per case in 6 cases each of FL-HCC and HCC.
      Results: The mean age of patients with FL-HCC was 19 years and all had normal
      serum alpha-fetoprotein levels. Fine needle aspiration smears showed large
      polygonal cells with abundant cytoplasm, vesicular nucleus and prominent
      nucleolus, associated with variably cellular fibrous stromal fragments.
      Intranuclear inclusions, cytoplasmic eosinophilic inclusions, and bile were also
      noted. FL-HCC showed strong membrano-cytoplasmic CK7 positivity and cytoplasmic
      granular and canalicular positivity for CD68. In contrast, HCC showed weak focal
      positivity for CK7 and only canalicular CD68 positivity. Morphometry revealed
      that FL-HCC cells were 2.19 times the size of HCC. Conclusion: CK7
      immunocytochemistry on cell blocks is useful for confirming and distinguishing it
      from HCC.

PMID- 29643653
TI  - Utility of Cytospin and Cell block Technology in Evaluation of Body Fluids and
      Urine Samples: A Comparative Study.
AB  - Background: Cytologic examination of body fluids commonly involves the use of
      direct or sediment smears, cytocentrifuge preparations, membrane filter
      preparations, or cell block sections. Cytospin and cell block techniques are
      extremely useful in improving cell yield of thin serous effusions and urine
      samples, and ensure high diagnostic efficacy. Materials and Methods: We studied
      cytospin preparations and cell block sections prepared from 180 samples of body
      fluids and urine samples to compare the relative efficiency of cell retrieval,
      preservation of cell morphology, ease of application of special stains, and
      diagnostic efficacy. Samples were collected and processed to prepare cytospin
      smears and cell block sections. Results: We observed that overall, cell yield and
      preservation of individual cell morphology were better in cytospin preparations
      as compared to cell blocks, while preservation of architectural pattern was
      better in cell block sections. The number of suspicious cases also decreased on
      cell block sections, with increased detection of malignancy. It was difficult to
      prepare cell blocks from urine samples due to low cellularity. Conclusions:
      Cytospin technology is a quick, efficient, and cost-effective method of
      increasing cell yield in hypocellular samples, with better preservation of cell
      morphology. Cell blocks are better prepared from high cellularity fluids;
      however, tissue architecture is better studied, with improved rate of diagnosis
      and decrease in ambiguous results. Numerous sections can be prepared from a small
      amount of material. Special stains and immunochemical stains can be easily
      applied to cell blocks. It also provides a source of archival material.

PMID- 29643654
TI  - Role of Endoscopic Ultrasound-guided Fine-needle Aspiration in Adrenal Lesions:
      Analysis of 32 Patients.
AB  - Objective: Endoscopic ultrasound-guided fine-needle aspiration cytology (EUS
      FNAC) is a precise and safe technique that provides both radiological and
      pathological diagnosis with a better diagnostic yield and minimal adverse events.
      EUS-FNAC led to the remarkable increase in the detection rate of incidentaloma
      found during radiologic staging or follow-up in various malignancy or unrelated
      conditions. Aims: We did this preliminary study with an aim to evaluate the role
      of EUS-FNA in diagnosing and classifying adrenal lesions, clinical impact, and
      compare the outcome with the previously published literature. Materials and
      Methods: We included 32 consecutive cases (both retrospective and prospective) of
      EUS-guided adrenal aspirate performed over a period of 3.3 years. The indications
      for the aspirate in decreasing order were metastasis (most common carcinoma gall
      bladder) > primary adrenal mass > disseminated tuberculosis > pyrexia of unknown
      origin. On EUS, 28 cases revealed space occupying lesion or mass (two cases
      bilateral) and four cases revealed diffuse enlargement (two cases bilateral) with
      a mean size of 21 mm. Results: The cytology reports were benign adrenal aspirate
      (43.8%), metastatic adenocarcinoma (15.6%), histoplasmosis (9.4%), tuberculosis
      (9.4%), round cell tumor (6.2%), adrenocortical carcinoma (3.1%), and descriptive
      (3.1%). Three cases (9.4%) yielded inadequate sample. The TNM staging was altered
      in 22.23% of the cases by result of adrenal aspirate. Conclusions: EUS-FNA of the
      adrenal gland is a safe, quick, and sensitive and real-time diagnostic technique,
      which requires an integrated approach of clinician, endoscopist, and
      cytopathologist for high precision in diagnosis. Although the role of EUS-FNA for
      right adrenal is not much described, we found adequate sample yield in all the
      four patients that underwent the procedure.

PMID- 29643655
TI  - Gata3 Immunohistochemical Staining is A Useful Marker for Metastatic Breast
      Carcinoma in Fine Needle Aspiration Specimens.
AB  - Aims: The utility of GATA3 immunohistochemistry (IHC) as an aid to the
      cytological diagnosis of metastatic breast carcinoma in fine needle aspiration
      (FNA) specimens was investigated. Materials and Methods: Cell block sections from
      111 FNA cases of metastatic malignancy were stained for GATA3, including
      metastases from 43 breast and 44 nonmammary adenocarcinomas, 19 melanomas, 4
      urothelial carcinomas, and 1 thyroid medullary carcinoma. Sites sampled included
      lymph nodes (87), bone (8), liver (5), lung (6), superficial masses (4), and
      pelvic mass (1). Results: Ninety-one percent (39/43) of metastatic breast
      carcinoma cases were positive for GATA3. All estrogen receptor (ER)-positive were
      also GATA3 positive cases. The majority (9/14; 64%) of ER-negative and 37% (3/8)
      of triple-negative cases were positive for GATA3. All nonmammary adenocarcinoma
      cases were negative with the exception of one case of metastatic pancreatic
      adenocarcinoma. Metastatic melanoma cases were all negative but 75% (3/4)
      urothelial carcinomas expressed GATA3. Conclusions: GATA3 IHC staining is a
      useful addition to IHC panels for FNA samples in specific settings such as
      distinguishing metastatic breast from lung carcinoma or melanoma.

PMID- 29643656
TI  - Comparison of Conventional Smear and Liquid-based Cytology Preparation in
      Diagnosis of Lung Cancer by Bronchial Wash and Transbronchial Needle Aspiration.
AB  - Introduction: Liquid-based cytology (LBC), initially developed for screening
      gynecologic specimens, is now being used in nongynecologic aspiration and
      exfoliative specimens. In this study, the diagnostic yield and utility of thin
      prep (TP) was compared with conventional preparations to ascertain its utility in
      improving the diagnosis of respiratory lesions. Materials and Methods: Bronchial
      washings (BW) and transbronchial needle aspirates (TBNA)
      (bronchoscopy/endobronchial ultrasound-guided) from 70 consecutive patients of
      mediastinal masses and endo/peribronchial growths were included. The diagnostic
      yields of both conventional smears and thin-prep were compared.
      Immunocytochemistry (ICC) was performed on direct/cytospin smears of TBNA/BW and
      TP slides when the tumor could not be subtyped by morphology. Histopathologic
      correlation was done. Results: Although well-preserved morphological features and
      cleaner background in TP allowed accurate diagnosis of malignancies, diagnostic
      yield was comparable to conventional preparations. Immunocytochemistry was
      successfully employed on TP smears which helped in accurate subtyping of the
      tumors. Few shortcomings of TP smears were uneven distribution of cells, thick
      cell clusters, and inadequate cellularity. Conclusion: Liquid-based TP
      preparation is an effective diagnostic tool for respiratory tract cytology,
      however, results are comparable to conventional smears.

PMID- 29643657
TI  - Analysis of Morphological Features of Benign and Malignant Breast Cell Extracted
      From FNAC Microscopic Image Using the Pearsonian System of Curves.
AB  - Context: Cytological changes in terms of shape and size of nuclei are some of the
      common morphometric features to study breast cancer, which can be observed by
      careful screening of fine needle aspiration cytology (FNAC) images. Aims: This
      study attempts to categorize a collection of FNAC microscopic images into benign
      and malignant classes based on family of probability distribution using some
      morphometric features of cell nuclei. Materials and Methods: For this study,
      features namely area, perimeter, eccentricity, compactness, and circularity of
      cell nuclei were extracted from FNAC images of both benign and malignant samples
      using an image processing technique. All experiments were performed on a
      generated FNAC image database containing 564 malignant (cancerous) and 693 benign
      (noncancerous) cell level images. The five-set extracted features were reduced to
      three-set (area, perimeter, and circularity) based on the mean statistic.
      Finally, the data were fitted to the generalized Pearsonian system of frequency
      curve, so that the resulting distribution can be used as a statistical model.
      Pearsonian system is a family of distributions where kappa (kappa) is the
      selection criteria computed as functions of the first four central moments.
      Results and Conclusions: For the benign group, kappa (kappa) corresponding to
      area, perimeter, and circularity was -0.00004, 0.0000, and 0.04155 and for
      malignant group it was 1016942, 0.01464, and -0.3213, respectively. Thus, the
      family of distribution related to these features for the benign and malignant
      group were different, and therefore, characterization of their probability curve
      will also be different.

PMID- 29643658
TI  - Comparing the Efficacy of Leishman-Giemsa Cocktail Stain, Giemsa Stain, and
      Papanicolaou Stain in Potentially Malignant Oral Lesions: A Study on 540
      Cytological Samples.
AB  - Background: This study was planned to compare and evaluate the staining efficacy
      of Leishman-Giemsa cocktail (LG), Papanicolaou, and Giemsa stain (G) in
      potentially malignant disorders and malignant lesions. Aims: To evaluate the
      quality of nuclear and cytoplasmic staining of LG with G, and rapid Papanicolaou
      stain (Pap) and to compare the total staining efficiency of LG against G and P.
      Materials and Methods: One hundred and eighty participants were studied under
      three groups - 60 as healthy controls, 60 with potentially malignant disorders,
      and 60 with malignant lesions; smears were taken thrice from the buccal mucosa.
      One smear was fixed with Bio-Fix spray and other two smears were allowed to air
      dry for 2-3 minutes. Then, the ethyl alcohol-fixed smear was stained with Pap and
      the two other air-dried smears were stained with G and LG stains. Analysis was
      done using Friedman test and Wilcoxon Signed Rank Test with SPSS Version 15.0.
      Results: In the normal group, staining of LG was highly significant (P < 0.001).
      Among potentially malignant lesions, LG was observed to be highly significant (P
      < 0.001) when compared with G and was not significant when compared with Pap (P =
      0.186). In the malignant group, LG was highly significant (P < 0.001). LG was
      superior with the highest average staining score of (2.018) than Pap and G.
      Conclusion: LG cocktail is a better stain with excellent cytoplasmic and nuclear
      staining intensity compared to Pap and G stains.

PMID- 29643659
TI  - Endoscopic Ultrasound-guided Cytodiagnosis of Adrenal Histoplasmosis with
      Reversible CD4 T-Lymphocytopenia and Jejunal Lymphangiectasia.

PMID- 29643660
TI  - Primary Splenic Angiosarcoma with Liver Metastasis: A Rare Neoplasm Diagnosed on
      Fine-needle Aspiration Cytology and Cell Block Immunocytochemistry.
AB  - Primary splenic angiosarcoma is a rare malignant vascular neoplasm of mesenchymal
      origin. The tumor is highly aggressive and has a high metastatic potential. It is
      usually diagnosed on histopathological examination of splenectomy specimen. Only
      few cases of angiosarcoma diagnosed by fine-needle aspiration (FNA) cytology
      alone have been reported in the literature. The cytologic features of
      angiosarcoma are heterogeneous, however, diagnosis can be suggested by FNA when
      vasoformative features are present. A 55-year-old female presented with abdominal
      pain and hepatosplenomegaly. Computed tomography scan revealed a heterogeneous
      splenic lesion with liver metastases. FNA from the splenic and liver lesions
      showed moderately pleomorphic tumor cells closely associated with anastomosing
      vascular channels. Cell block immunocytochemistry (ICC) showed tumor cells
      positive for CD31, CD34, CD68 as well as for CD99. FNA supplemented by cell block
      ICC can render a definite diagnosis of primary splenic angiosarcoma with liver
      metastasis.

PMID- 29643661
TI  - Unusual Metastasis of Medullary Thyroid Carcinoma to the Breast: A Cytological
      and Histopathological Correlation.
AB  - Breast metastases are a relatively rare condition and account for approximately
      0.5-2% of all breast tumors. Recognition of metastatic tumors in the breast is
      important because it would prevent unnecessary mutilating surgery and would lead
      to appropriate treatment of the primary tumor. Breast metastases from medullary
      thyroid cancer (MTC) are very rare with only 21 reported cases in the literature.
      Some MTCs mimic primary invasive lobular carcinoma of the breast
      histopathologically and radiologically, making the distinction between the two
      diagnostically challenging. We present the case of a 45-year-old female
      presenting with a lump breast, which was later found out to be metastasis from
      medullary carcinoma thyroid.

PMID- 29643662
TI  - Retinoblastoma in an Adult.
AB  - Retinoblastoma is a rare malignant tumor of the retina usually seen in children
      before 5 years of age. The tumor is extremely rare in adults. We report here an
      unusual case of retinoblastoma in a 55-year-old adult female who presented to us
      with an orbital mass at a late stage of the disease. Detailed laboratory
      investigations and imaging studies could not make a precise diagnosis. The
      treating ophthalmologist suspected primary intraocular tumor, metastatic
      carcinoma, malignant melanoma, or lymphoma and referred the patient for fine
      needle aspiration cytology (FNAC). Cytopathological examination of Giemsa-stained
      FNAC smear was consistent with that of retinoblastoma and established the
      diagnosis.

PMID- 29643663
TI  - Cystic Schwannoma of Tongue Masquerading as Mucocele: A Cytological Pitfall.

PMID- 29643664
TI  - Papillary Carcinoma Thyroid Presenting as Huge Scalp Metastases.

PMID- 29643665
TI  - Cytological Diagnosis of Mazabraud's Syndrome.

PMID- 29643666
TI  - Cytological Findings of a Rare Case of Transitional Cell Carcinoma Bladder
      Presenting with Supraclavicular Lymphnode Metastasis.

PMID- 29643667
TI  - Role of Preablative Stimulated Thyroglobulin in Prediction of Nodal and Distant
      Metastasis on Iodine Whole-Body Scan.
AB  - Background: Preablative stimulated thyroglobulin (ps-Tg) is an important
      investigation in the follow-up of patients with Differentiated thyroid
      cancer(DTC) after surgery. Levels of ps-Tg >2-10 ng/ml have been suggested to
      predict metastasis to cervical and extracervical sites. There is still debate on
      the need for routine iodine whole-body scan (131I WBS) in the management of low
      to-intermediate-risk DTC patients. Objective: We analyzed our data of patients
      with DTC who underwent total thyroidectomy to discuss the predictability of ps-Tg
      on metastatic disease on the 131I WBS. Materials and Methods: Retrospective
      analysis of patient records. Results: One hundred and seventeen patients with DTC
      (95 papillary thyroid cancer [71 had classic histology, 8 had tall cell variant,
      16 had follicular variant] and 22 follicular thyroid cancer [18 minimally
      invasive, 2 hurtle cell, and 2 widely invasive cancers]) had undergone total
      thyroidectomy. All these patients underwent ps-Tg assessment and an 131I WBS.
      About 65% of them went on to have radioiodine ablation along with a posttherapy
      131I WBS. We divided the cohort into four groups based on their ps-Tg levels:
      Group 1 (ps-Tg <1), Group 2 (ps-Tg 1-1.9), Group 3 (ps-Tg 2-5), and Group 4 (ps
      Tg >5). None of the patients in Group 1, 7% of those combined in Groups 2 and 3
      (2 out of 28 patients), and 26% (12 out of 47) of those in Group 4 had either
      cervical or extracervical metastasis. Those with extracervical metastatic disease
      to lungs and bones had a mean (standard deviation) ps-Tg value of 436 (130) and
      median of 500 ng/ml and those with cervical metastatic disease had a mean Tg
      value of 31 (64) and median 6.6 ng/ml. Conclusions: A ps-Tg value in the absence
      of anti-Tg antibodies <1 ng/ml reliably excludes metastatic disease in DTC, while
      a value >5 ng/ml has a 26% risk of having either cervical or extracervical
      metastasis.

PMID- 29643668
TI  - The Radioprotective Effects of Curcumin and Trehalose Against Genetic Damage
      Caused By I-131.
AB  - Background: Thyroid cancer has been growing rapidly during the last decades.
      Radioiodine-131 (I-131) as an appropriate therapy modality is currently using in
      the treatment of cancer and hyperthyroidism diseases. This radiotracer is
      considered as a cause of oxidative DNA damage in nontarget cells and tissues. The
      aim of this study was to investigate the effects of curcumin and trehalose on the
      level of DNA double-strand breaks (DSBs) caused by I-131 in human lymphocytes.
      Materials and Methods: First, 6-mL blood samples were taken from each of the five
      volunteers. After 1 h of preincubation with the antioxidants, a total of 20 MUCi
      I-131/2 mL (blood + NaCl) was added to each sample, and then, the samples were
      reincubated for 1 h. Lymphocytes were separated and the mean DSB levels were
      measured for each sample through gamma-H2AX assay to evaluate the effects of
      antioxidants. Results: After 1-h incubation with I-131, the DSBs increased by
      102.9% compared to the control group (0.343 vs. 0.169 DSB/cell; P = 0.00).
      Furthermore, compared to the control + I-131 group, curcumin and trehalose
      reduced the DSBs by 42% and 38%, respectively. There was a significant decrement
      (P = 0.00) in the levels of DSBs of the curcumin + I-131 and trehalose + I-131
      subgroups compared to the control + I-131 subgroup. Furthermore, there was no
      significant relationship between the radioprotective effect of curcumin and
      trehalose (P = 0.95). Conclusion: The use of curcumin and trehalose as
      antioxidant can reduce the numbers of DSBs caused by I-131. Meanwhile, the
      radioprotective effect of curcumin was more than trehalose.

PMID- 29643669
TI  - Which is Better - A Standalone Ventilation or Perfusion Scan or Combined Imaging
      to Predict Postoperative FEV1 in One Seconds in Patients Posted for Lung
      Surgeries with Borderline Pulmonary Reserve.
AB  - Introduction: Forced expiratory volume in one second (FEV1) is an independent
      predictor for respiratory morbidity. Reports are varied and controversial
      substantiating the use of either lung perfusion (Q) or ventilation (V)
      scintigraphy as a single stage investigation to predict postoperative (ppo) FEV1
      in patients scheduled for lung resection surgeries. It is said that there is no
      additional benefit by performing both V/Q scan. As per one of the
      recommendations, no further respiratory function tests are required for a
      lobectomy if the postbronchodilator FEV1 is >1.5 l. We wanted to study the ppo
      FEV1 in patients with FEV1 of <1.5 L scheduled for lung surgeries. Being a high
      risk population, we wanted to assess (a) whether the ppo changes by this combined
      V/Q imaging and (b) whether the incidence of respiratory complication in the
      postoperative setting of this subgroup is different, (c) and study the short- and
      long-term clinical outcome. Materials and Methods: Fifty-two high-risk patients
      (with comorbidities) and borderline preoperative FEV1 of 1.5 L or less planned
      for lung resection were enroled in this prospective study. V and Q scans were
      performed, and tracer uptake percentage was tabulated. Results: Tracer uptake in
      each lung was quantitated. Manual method of ROI drawing is preferred in high risk
      patients with reduced pulmonary reserve over the automatic method. Based on
      uptake patterns by V/Q scans, 4 different types of patterns were tabulated.
      Eighty-eight percentage of centrally placed tumors showed the difference in
      uptake patterns. Chronic obstructive pulmonary disease patients usually showed
      more modest ventilatory defects (categorised as type 2 or 3). Lung tumours
      produce erratic uptake patterns (Type 4) which depend heavily on their location
      and extent. The range of FEV1 predicted was 0.6-1.38 L/min. Conclusion: We
      recommend that combined imaging should be performed in patients with borderline
      pulmonary reserve to derive the benefit of surgery as it provides a realistic ppo
      FEV1 in patients with moderate to severely damaged lung. Centrally placed hilar
      or bronchial tumors (even those <2 cm in size), produce discrepancies in V/Q
      distribution pattern. Patient who was thought ineligible for surgery due to low
      baseline FEV1 may be actually be operable by this combined imaging if uptake
      pattern is better in V or Q scan with a good outcome. Accurate estimation of
      postop FEV1 in fact helps the surgical team to implement measures to prepare high
      risk patients to reduce postoperative complications, enable faster weaning from
      ventilatory support and ensure favourable prognosis.

PMID- 29643671
TI  - Role of Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in
      Various Orbital Malignancies.
AB  - Orbital swelling comprises wide spectrum of pseudotumors, benign and malignant
      tumor. Malignant tumor may be primary or secondary tumor, and they constitute
      about 36% of orbital tumors in adult. Fluorodeoxyglucose-positron emission
      tomography/computed tomography (FDG-PET/CT) scan is extensively used in
      hematological malignancies and in solid tumors for staging, treatment response,
      and restaging. Recently, the use of FDG-PET/CT in orbital malignancies has gained
      importance. The aim of this pictorial essay is to illustrate few important
      orbital malignancies detected in F-18 FDG-PET/CT and discuss its role in
      assessing the primary lesion and associated systemic finding.

PMID- 29643670
TI  - Role of Early Dynamic Positron Emission Tomography/Computed Tomography with 68Ga
      prostate-specific Membrane Antigen-HBED-CC in Patients with Adenocarcinoma
      Prostate: Initial Results.
AB  - Rationale: Prostate-specific membrane antigen positron emission
      tomography/computed tomography (PSMA PET/CT) is widely used for imaging of
      prostate cancer (PC) nowadays. However, appearance of bladder activity many a
      times hampers lesion detection vis-a-vis primary as well as regional nodes. We
      aimed to assess if early dynamic PET/CT can be a potential solution to this
      issue. Methodology: A total of 15 biopsy-proven PC patients who were referred to
      our department for 68Ga-PSMA PET/CT for staging/restaging were prospectively
      studied. Dynamic PET/CT was done with on table intravenous injection of 2-3 mCi
      (74-111 MBq) of the radiotracer. Dynamic images were acquired over the pelvis
      with a frame time of 1 min for 10 min. Static images of 2 min per bed position
      were acquired between 45 and 60 min after injection. A 3D volume of interest was
      plotted on the primary lesion, involved nodes if any, pelvic bones at involved
      and uninvolved sites, gluteal muscles, and bladder. Results: Six patients were
      referred for staging and 9 for restaging. Mean age of 15 patients was 66.7 years,
      median prostate-specific antigen level was 17.25 ng/ml (Range 0.05-218), mean
      Gleason score was 8. All patients showed high target to nontarget ratio in the
      early dynamic images comparable to that seen on the delayed images in different
      sites (prostatic primary: n = 15 patients; lymph nodes: n = 10 patients; bone: n
      = 5 patients). All pathologic lesions showed tracer uptake within the first 3 min
      and reached maximum uptake during the dynamic study in last 3 min, indicating an
      increasing uptake pattern, whereas urinary bladder (UB) activity was
      insignificant within the first 3 min of dynamic imaging in all patients, reached
      maximum during last 3 min. SUVmax was significantly higher in primary lesions in
      the first 4 min compared to UB accumulation. Static images showed more tracer
      accumulation than dynamic images in primary, nodal, and bony lesions. However,
      all regional nodes seen on delayed static imaging also showed uptake on dynamic
      imaging. Conclusion: Early dynamic imaging 68Ga-PSMA PET/CT can demarcate the
      primary tumor clearly due to nonaccumulation of bladder activity and appears to
      have comparable efficacy in detecting pelvic nodal sites as delayed imaging.

PMID- 29643672
TI  - An Interesting Case of Retropharyngeal Lymph Nodal Metastases in a Case of Iodine
      Refractory Thyroid Cancer.
AB  - Metastases to cervical lymph node are fairly common in differentiated thyroid
      cancer. In iodine-refractory disease, the disease may persist in the thyroid bed,
      cervical lymph nodes, lungs, or the bones commonly. Retropharyngeal lymph nodal
      involvement in thyroid cancer is unusual and may even be the presenting
      complaint. We represent a case of iodine-refractory thyroid cancer with
      retropharyngeal lymph nodal involvement in addition to lung metastases.

PMID- 29643673
TI  - Incomplete form of Primary Hypertrophic Osteoarthropathy (Touraine-Solente-Gole
      Syndrome) Masquerading as Polyartrhalgia Diagnosed in Technetium-99m-Methylene
      Diphosphonate Scintigraphy: An Interesting Case Report.
AB  - The primary hypertrophic osteoarthropathy (PHOA) (pachydermoperiostosis) is a
      rare genetic/hereditary disease characterized by skin changes (pachydermia),
      clubbing of fingers and periosteal thickening (periostitis) with sub-periosteal
      new bone formation. Here we describe a case of an adolescent male who presented
      with clubbing and polyarthralgia. On evaluation with scintigraphy and SPECT-CT,
      he was diagnosed to have incomplete form of PHOA(skeletal manifestations without
      skin changes). The identification of incomplete form of primary hypertrophic
      osteoarthropathy which can be easily misdiagnosed as rheumatoid arthritis is
      discussed here.

PMID- 29643674
TI  - Unusually Large Brown tumor of Mandible in a Case of Secondary
      Hyperparathyroidism Mimicking Cherubism.
AB  - We report here a case of unusually large brown tumor of mandible mimicking
      cherubism in a patient with secondary hyperparathyroidism (HPT). The patient is a
      young male with a large head and a protruding jaw with an open mouth appearance.
      Initial clinical appearance looked like cherubism. However further clinical,
      biochemical, and radiological evaluation revealed a large brown tumor in a case
      of prolonged secondary HPT, which was confirmed on histopathology. All of the
      typical advanced radiological features of HPT were noted, highlighting the
      severity of progression of the disease. This case emphasizes the need for
      surveillance of serum calcium levels on routine biochemical investigations as to
      enable an early diagnosis of HPT. With timely proper management, such cases
      should be on the decline in the future.

PMID- 29643675
TI  - Serendipitous Unearthing of Silent Multiple Giant Rasmussen's Aneurysms by
      Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography/Computerized
      Tomography.
AB  - The authors report multiple giant bilateral pseudoaneurysms of pulmonary artery,
      also known as Rasmussen's aneurysms, which remained silent and unrevealed despite
      the large size and multiplicity unearthed by fluorine-18 fluorodeoxyglucose
      positron emission tomography/computerized tomography.

PMID- 29643676
TI  - Discordant Primary Resistance to Imatinib Mesylate in the Same Individual and
      Splenic Involvement in Recurring Gastric Gastrointestinal Stromal Tumors:
      Assessment by Fluorodeoxyglucose-Positron Emission Tomography/Computed
      Tomography.
AB  - Discordant primary resistance and response of the metastatic lesions in the same
      individual coupled with splenic involvement in gastrointestinal stromal tumors
      (GISTs) are relatively uncommon. We herein report such a case of recurring GIST
      of the stomach that presented with the involvement of spleen with 18F
      fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT)
      imaging documentation. Ultrasonography-guided fine needle aspiration cytology
      from the splenic and paravesical lesions demonstrated metastatic spindle cell
      tumor consistent with diagnosis of metastasis from GIST of the stomach. The
      splenic and the paravesical lesions appeared resistant to the conventional 400 mg
      of imatinib mesylate, while most other abdominopelvic metastatic lesions
      demonstrated good metabolic response on FDG-PET/CT, with the noteworthy findings
      of interlesional heterogeneity of the metastatic lesions in terms of differential
      primary response in the same individual.

PMID- 29643677
TI  - Gossypiboma of Axilla: Imaging Pitfalls on Fluorodeoxyglucose Positron Emission
      Tomography and Computed Tomography.
AB  - 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) with computed
      tomography (CT) has become the standard of care in staging, restaging, and
      response assessment of various malignancies including malignant melanoma.
      However, nonspecific uptake of FDG can occur in infectious and inflammatory
      conditions and can mimic a tumor. We present here a case of gossypiboma of the
      axillary region with FDG uptake detected in a patient with malignant melanoma of
      the upper extremity and discuss the potential pitfalls of this entity on FDG
      PET/CT.

PMID- 29643678
TI  - Metabolic Bone Superscan in Carcinoma Breast with Occult Graves' Disease: Looking
      Beyond Skeletal Metastases.
AB  - Extrathyroidal manifestations of autoimmune thyroid disorders include thyroid
      associated ophthalmopathy, thyroid dermopathy, and thyroid acropachy. Thyroid
      acropachy is an extreme manifestation of autoimmune thyroid disorder
      characterized by clubbing and swelling of fingers and toes, with or without
      periosteal reaction of the distal bones. We present a 50-year-old woman,
      posttreatment for carcinoma breast (6 years back) and referred for bone scan for
      generalized body ache. Bone scan findings resulting in detailed clinical
      evaluation prompted toward the suspicion of a thyroidal disease with ultimate
      diagnosis of Graves' disease.

PMID- 29643679
TI  - A Rare Case of Sarcoidosis Presenting as Diffuse Contracturing Granulomatous
      Myositis on Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography.
AB  - Fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) is
      an established imaging modality in diagnosis and treatment response monitoring of
      sarcoidosis. Multisystemic involvement of sarcoidosis is characteristically seen
      on PET/CT; however, isolated organ involvement is rare. We describe here a case
      of a 52-year-old male with generalized muscle weakness, an extremely rare
      clinical manifestation of sarcoidosis.

PMID- 29643680
TI  - Fluorodeoxyglucose Positron Emission Tomography-computed Tomography Evaluation of
      an Interesting Case of Uterine Carcinosarcoma with Isolated Appendicular Skeletal
      Metastases.
AB  - Uterine carcinosarcomas, also known as malignant mixed mullerian tumors, are one
      of the rare and most aggressive neoplasms of the uterus. They have an aggressive
      course and can spread to distant organs. Owing to the low incidence of these
      tumors, the optimal adjuvant management after surgery is not well established.
      Many patients develop distant metastases during follow-up. An interesting case of
      uterine carcinosarcoma who developed metastases to the femur, tibia, and
      calcaneum during follow is presented.

PMID- 29643681
TI  - Mismatch in Brain Perfusion and Metabolism Detected with 99mTc-Hexamethyl
      Propylene Amine Oxime Single Photon Emission Computed Tomography and 18F
      Fluorodeoxyglucose Positron Emission Tomography in Moyamoya Disease.
AB  - We report a 47-year-old woman who developed an ischemic stroke with diplopia and
      dysarthria. Emergency computed tomography (CT) showed no pathological findings,
      and magnetic resonance (MR) showed mild ischemic-degenerative lesions. MR
      angiography and angiogram showed severe stenosis of both internal carotid and
      main intracranial arteries with plenty collateral vessels with "puff of smoke"
      suggesting a moyamoya disease (MMD). Brain perfusion single-photon emission CT
      showed global diminished perfusion in the brain lobes and a marked relative
      hyperperfusion in the cerebellum. However, brain 18F-fluorodeoxyglucose-positron
      emission tomography showed physiological metabolism in the brain cortex with only
      slightly relative cerebellar hypermetabolism. MMD is a well-known arterial
      pathology that frequently develops with only mild symptoms until the middle age.
      Functional neuroimaging findings indicate a mismatch between brain glucose
      metabolism and brain perfusion, probably due to neuronal subclinical chronic
      ischemia in the brain cortex with preserved viability of neurons.

PMID- 29643682
TI  - Lumbar Gout Tophus Mimicking Epidural Abscess with Magnetic Resonance Imaging,
      Bone, and Gallium Scans.
AB  - Gout is a common metabolic disorder, typically diagnosed in peripheral joints.
      Tophaceous deposits in lumbar spine are a very rare condition with very few cases
      reported in literature. The following is a case report of a 52-year-old patient
      with low back pain, left leg pain, and numbness. Serum uric acid level was in
      normal range. magnetic resonance imaging, bone scan, and gallium-67 images
      suggested an inflammatory-infectious process focus at L4. After a decompressive
      laminectomy at L4-L5 level, histological examination showed a chalky material
      with extensive deposition of amorphous gouty material surrounded by macrophages
      and foreign-body giant cells (tophaceous deposits).

PMID- 29643683
TI  - Postrenal Transplant Allograft "Page Kidney" Identified and Salvaged using 99mTc
      diethylenetriaminepentaacetic acid Renogram and Single-photon Emission-computed
      Tomography.
AB  - 99mTc diethylenetriaminepentaacetic acid (DTPA) renogram is a commonly performed
      evaluation postrenal transplant to assess graft function and for early detection
      of suspected immediate and late transplant-associated complications. Although
      several modalities can be utilized to detect perinephric collection in
      posttransplant period, the utility of 99mTc DTPA single-photon emission-computed
      tomography (SPECT-CT) is not recognized. Herein, we discuss the incremental role
      of seldom considered SPECT-CT in early detection, leading to timely appropriate
      management and graft salvage in a case of posttransplant deteriorating renal
      allograft as a result of subcapsular hematoma.

PMID- 29643684
TI  - Posterior Layering of Fluorine-18 Fluorodeoxyglucose in the Urinary Bladder.
AB  - An 89-year-old man undergoing fluorine-18 fluorodeoxyglucose positron emission
      tomography/ computed tomography (18F-FDG PET/CT) study posttherapy for
      hepatocellular carcinoma was noted to have 18F-FDG posterior layering of the
      urinary bladder. This phenomenon of posterior layering of 18F-FDG in the urinary
      bladder during PET/CT studies is physiological, and it is important to recognize
      to avoid misinterpretation and unnecessary investigations. The hypotheses for the
      cause of this phenomenon are highlighted in these interesting images including
      the reversed phenomenon where there is anterior layering of 18F-FDG.

PMID- 29643685
TI  - Unilateral Brown Fat Suppression on FDG PET/CT-detecting Sympathetic Denervation.
AB  - We present here a case of primitive neuroectodermal tumor (PNET) who initially
      presented with involvement of the right 3rd rib and underwent neoadjuvant
      chemotherapy, rib excision, and adjuvant chemoradiotherapy and later underwent
      posterolateral thoracotomy, pleural nodule excision, and the right 11th rib
      metastatic lesion excision. Follow-up 18F-FDG PET/CT/computed tomography revealed
      unilateral brown fat suppression in the form of decreased metabolic uptake in the
      ipsilateral cervical, axillary, and paravertebral brown fat as compared to
      metabolically active contralateral brown fat, likely due to paravertebral
      sympathetic chain damage.

PMID- 29643686
TI  - Primary Fibroblastic Osteosarcoma of the Lumbar Vertebra on Fluorine-18
      Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography.
AB  - A 37-year-old man who presented with one year history of lower back and right
      buttock pain was investigated with contrast enhanced computed tomography (CT),
      magnetic resonance imaging (MRI), and fluorine-18 fluorodeoxyglucose positron
      emission tomography/computed tomography which revealed a diagnosis of primary
      fibroblastic osteosarcoma of the lumbar vertebra. This case highlights the
      importance of PET/CT imaging.

PMID- 29643687
TI  - Atypical Hemangioma Mimicking Metastasis on 18F-Sodium Fluoride Positron Emission
      Tomography-Computed Tomography and Magnetic Resonance Imaging: Gallium-68
      Prostate-Specific Membrane Antigen Positron Emission Tomography Improves the
      Specificity of Bone Lesions.
AB  - Vertebral hemangioma is a benign condition, but sometimes, it might represent as
      diagnostic dilemma especially in elderly patient mimicking serious pathology like
      metastasis. We report a case of a 66-year-old man with prostate cancer. 18F
      sodium fluoride positron emission tomography-computed tomography (18F-NaF PET-CT)
      demonstrates increased radiotracer uptake at body of D4 vertebra. Magnetic
      resonance imaging shows features of atypical hemangioma; however, metastasis
      cannot be ruled out. To rule out bone metastasis, gallium-68-prostate-specific
      membrane antigen PET-CT is performed which shows no abnormal lesion. Eight-month
      follow-up by 18F-NaF PET-CT showed persistent osteoblastic lesion at D4 without
      any significant change thus, confirming the initial diagnosis of atypical
      hemangioma.

PMID- 29643688
TI  - Simultaneous 18F- FDG PET/MRI in Autoimmune Limbic Encephalitis.
AB  - Limbic encephalitis is an autoimmune disorder characterized by inflammation of
      the brain with rapidly progressing dementia which requires definitive
      neurological evaluation. We describe both clinical as well as imaging findings in
      a case of limbic encephalitis using positron emission tomography/magnetic
      resonance imaging.

PMID- 29643689
TI  - The Utility of Tc-99m Hydroxymethylene Diphosphonate Single-photon Emission
      Computed Tomography/Computed Tomography in Symptomatic Os Trigonum.
AB  - Os trigonum is a congenital condition in which a bone ossicle fails to fuse to a
      secondary ossification center in the posterior aspect of the talar bone.
      Repetitive plantar flexion of the foot may elicit inflammation of the ossicles
      fibrous connective band, subsequently causing pain. It is common to misdiagnose
      os trigonum as an avulsion fracture. We report a case of a 23-year-old male with
      symptomatic os trigonum diagnosed on Tc-99m hydroxymethylene diphosphonate single
      photon emission computed tomography-computed tomography (SPECT-CT). We also wish
      to emphasize on the use of SPECT/CT in not only allocating the ossicle
      anatomically but also for the purpose of evaluation an active source of pain in a
      region of multiple complex small bones.

PMID- 29643690
TI  - Decisive Role of Nuclear Imaging in a Rare Pancreatic Incidentaloma.
AB  - Pancreatic incidentalomas are increasingly recognized entities that occur as a
      fallout of widespread availability of high definition imaging technology. These
      lesions offer diagnostic dilemmas to both clinicians and radiologists alike.
      Nevertheless, it is the advancement in diagnostic radiology that comes to the
      rescue in the management of these not-so-uncommon lesions.

PMID- 29643691
TI  - Incidental Meningioma on 68Ga-DOTANOC Positron-Emission Tomography.

PMID- 29643692
TI  - Correlation of tibial bone defect shape with patient demographics following total
      knee revision.
AB  - Background: Bone defects of the proximal tibia following revision total knee
      arthroplasty (TKA) are challenging to manage, but must be addressed to provide
      lasting stability. This paper will categorize tibial bone defects into shape
      groups and correlate resulting groups to patient demographic data. Methods:
      Retrospective analysis of four hundred and four patients post revision TKA
      between January 2005 and February 2014 was conducted. One hundred and eighteen
      met the inclusion criteria and were subcategorized by defect shape on their post
      operative lateral and anterior-posterior (AP) radiographs. The subgroups of
      defect shape were subsequently analyzed with Fisher's exact test and one way
      ANOVA. Results: Trapezoidal shaped defects were the most common in both
      radiographic views, and the magnitude of the defect at the top joint line varied
      significantly amongst shape groups in both AP and lateral views. Trapezoid shaped
      defects were correlated with smaller defect top lengths in both views. There was
      no statistical correlation between defect shape BMI, TIV and reason for revision
      in lateral view. However, T-bilateral defect shapes were correlated with higher
      BMIs in AP view. Conclusion: A volumetric classification system of tibial defects
      is necessary for preoperative planning in revision TKA. Common tibial bone defect
      shape groups were identified and analyzed in AP and lateral radiographs after
      revision TKA. Trapezoidal defects were the most common, and all other shapes
      followed a pattern of proximal enlargement tapering distally. Trapezoidal defects
      were smaller than other shapes and AP T-bilateral shaped defects were correlated
      with higher BMIs.

PMID- 29643693
TI  - Joint perception and patient perceived satisfaction after total hip and knee
      arthroplasty in the American population.
AB  - Background: Total hip (THA) and knee arthroplasty (TKA) are two of the most
      successful procedures in orthopedics. Current evaluation trends focus on patient
      reported outcomes. We sought to compare the changing WOMAC scores from various
      time points from pre-operative to 1-year follow-up between separate THA and TKA
      cohorts. In addition, we compared THA and TKA patients' joint perception,
      satisfaction, and function via a questionnaire. Methods: One hundred elective THA
      (n = 50) and TKA (n = 50) patients at one institution were randomly selected and
      contacted between 2 and 4 years after the index surgery. A questionnaire assessed
      joint perception, satisfaction and function of their total joint. Clinical
      function scores utilizing the Western Ontario and McMaster Universities
      Osteoarthritis Index (WOMAC) from the pre-operative, 3-month and 1-year post
      arthroplasty visits were compared between groups. Results: 78% of the THA group
      perceived their replaced joint as "native" vs 32% of TKA patients. 54% of THA
      patients (vs 16% of TKA patients) reported uninhibited function of their total
      joint. 24% of TKA patients noted to be least satisfied with their total joint
      compared to 2% in the THA group. Both groups demonstrated significant improvement
      in WOMAC scores after surgery, but the mean 3-month (12.4 (THA) vs 19.3 (TKA))
      and 1-year (6.5 (THA) vs 14.1 (TKA)) follow-up WOMAC scores were significantly
      better in the THA group. Conclusion: Evaluation of a patient's joint perception
      is a valuable tool that should be used to assess function in conjunction with
      validated clinical functional scores. Our data suggest further improvements in
      total knee implant design and implantation strategies are necessary.

PMID- 29643694
TI  - Bone preserving techniques for explanting the well-fixed cemented acetabular
      component.
AB  - Background: Removal of a well-fixed, cemented acetabular component at the time of
      revision hip surgery can be complex. It is essential to remove the implant and
      cement mantle in a timely fashion while preserving bone stock and osseous
      integrity. The biomechanical properties of polymethylmethacrylate cement and
      polyethylene can be utilised to aid with the removal of well cemented implants
      which are often harder than the surrounding bone. While removal of loose
      components may be relatively straightforward, the challenge for the revision
      arthroplasty surgeon often involves the removal of well-fixed implants. Here, we
      present three established techniques for the removal of a well-fixed cemented
      acetabular component and one novel modification we have described before. Method:
      We collate and review four techniques for removing well-fixed cemented acetabular
      implants that utilise the different biomechanical properties of bone cement and
      polyethylene. These techniques are illustrated with a photographic series
      utilising saw bones. A step-by-step approach to our new technique is shown in
      photographs, both in the clinical setting and with a "Sawbone". This is
      accompanied by a clinical video that details the surgical technique in its
      entirety. Results: These techniques utilise different biomechanical principles to
      extract the acetabular component. Each technique has advantages and
      disadvantages. Our new technique is a simplification of a previously published
      extraction manoeuvre that utilises tensile force between cement and the implant
      to remove the polyethylene cup. This is a safe and reproducible technique in
      patients with a well-fixed cemented acetabular implant. Conclusion: Understanding
      the biomechanical properties of polymethylmethacrylate bone cement and
      polyethylene can aid in the safe removal of a well-fixed cemented acetabular
      component in revision hip surgery. The optimal technique for removal of a
      cemented acetabular component varies depending on a number of patient and implant
      factors. This summary of the available techniques will be of interest to revision
      arthroplasty surgeons.

PMID- 29643695
TI  - Preliminary study of coal fly ash (FA) phytoremediation by selected cereal crops.
AB  - This study focuses on the environmentally friendly utilization of coal combustion
      residue, fly ash (FA) containing significant amounts of heavy metals. Knowledge
      about the potential use of FA as a component of growth media for plants is
      fragmentary. Preliminary experiments tested the possibility to grow cereal crops
      on media composed exclusively of FA. The analysis of seven different FA from
      lignite and semi-bituminous coal from North Dakota and Montana sources using
      inductively coupled plasma emission spectrophotometry showed high concentrations
      of heavy metals in coal (up to, in mg/kg): As:65, Cd:3.9, Co:38, Cr:77, Li:109,
      Mn:1547, Pb:106, Ni:41, V:306. Seedlings of rye, wheat, oats, barley, triticale,
      and regreen (hybrid between wheat and ryegrass) were planted in Petri dishes (10
      cm in diameter) in growth media containing FA from lignite coal, FA from semi
      bituminous coal, bottom ash, and Fargo clay soil as the control. Each treatment
      was performed in 3 replications, and each experiment was repeated 3 times.
      Germination rates, plant growth analysis, and dry matter yield were determined 2
      3 weeks after planting. Germination rates and dry matter yield of oats,
      winterwheat and regreen were greater (10-20% above controls) in media composed of
      coal ash, but rye, barley, and wheat seedlings were affected by FA in media.
      These results show the potential for the utilization of FA as a growth media for
      cereal crops. Therefore, these plants might be used as green cover preventing
      wind erosion over the coal ash piles. However, this issue requires additional in
      depth investigation, including a thorough chemical analysis of plant material.

PMID- 29643696
TI  - Heart Regeneration in Adult Mammals after Myocardial Damage.
AB  - Heart regeneration remains a critical question in current basic research and
      clinical practice. The adult mammalian heart exhibits a very limited regeneration
      capacity. In contrast, adult zebrafish and neonatal mice retain a remarkable
      ability of heart regeneration after damage. Understanding the mechanisms of heart
      regeneration would be very valuable to help design efficient treatment strategies
      against myocardial damage and heart failure. While inherent regeneration of the
      heart occurs after damage with varying efficiency among species, regeneration may
      also be induced exogenously. In this study, we briefly review the different
      approaches and current progress in improving heart regeneration.

PMID- 29643697
TI  - Vascular Healing Response after Everolimus-Eluting Stent Implantation in Acute
      Coronary Syndrome Culprit Lesions: Comparison with Implantation in Stable Angina
      Pectoris.
AB  - Background: To evaluate the neointimal conditions of everolimus-eluting stents
      (EESs) implanted in culprit lesions of patients with acute coronary syndrome
      (ACS) compared with stable angina pectoris (SAP) using optical coherence
      tomography (OCT). EESs are second-generation drug-eluting stents that have
      recently been shown to be useful in patients with ACS as well as in patients with
      SAP. However, few studies have analyzed the intra-stent conditions of EESs that
      can lead to favorable results in such ACS lesions. Methods: We evaluated 41 ACS
      patients with EES implantation (age, 66.7 +/- 10.3 years) and 59 SAP patients
      enrolled as controls (age, 68.3 +/- 10.7 years). OCT examinations were performed
      after 9 months of follow-up after stent implantation, and the condition of the
      neointimal coverage over every stent strut was assessed in 1-mm intervals. In
      addition, neointimal thickness (NIT) over each strut was measured and tissue
      characteristics were examined. Results: There was no significant difference in
      mean NIT between the ACS (90.8 +/- 88.2 mm) and SAP (87.3 +/- 74.2 mm, p = 0.11)
      group. The rate of uncovered struts was significantly lower in the ACS group
      (11.5%) than in the SAP group (12.5%, p = 0.03). Neointimal tissue
      characteristics were also similar between groups. Conclusions: Vascular responses
      after EES implantation differed significantly between ACS and SAP lesions using
      OCT. However, these differences were considered small in clinical terms. Our OCT
      data support the favorable results of patients with EES implantation at mid-term
      follow-up, even in those with ACS.

PMID- 29643698
TI  - Real-World Comparison of Drug-Eluting and Bare-Metal Stents in Superficial
      Femoral Artery Occlusive Disease with Trans-Atlantic Intersociety Consensus B
      Lesions: A 2-Year, Single-Institute Study.
AB  - Background: Endovascular stenting has surpassed bypass surgery to become the
      first-line treatment for superficial femoral artery (SFA) occlusive disease, and
      various types of stents including bare-metal stents (BMSs), covered stents, and
      drug-eluting stents (DESs), have been approved for treatment. This retrospective,
      single-institute study compared the short-term, real-world outcomes of BMSs and
      DESs for treating SFA occlusive disease. Methods: A retrospective chart review
      was used to enroll 94 patients who received a DES (n = 24) or BMS (n = 70)
      between 2009 and 2014. All patients had SFA occlusive disease with critical limb
      ischemia and an intermediate length of SFA occlusion [Trans-Atlantic Intersociety
      Consensus (TASC)-II B lesions] and were regularly followed for 2 years. All
      patient characteristics, procedural details, and outcomes were recorded. Results:
      The 1-year primary patency rates in the BMS and DES groups were 71.4% and 87.5%
      (p = 0.169), respectively, and the corresponding 2-year rates were 61.4% and
      79.2% (p = 0.139). The target lesion revascularization rate was 38.6% versus
      20.8% (p = 0.139), the in-stent restenosis rate was 22.9% versus 0% (p = 0.009),
      the major limb amputation rate was 4.3% versus 0% (p = 0.568), the peripheral
      arterial disease-related mortality rate was 8.6% versus 0% (p = 0.332), and the
      all-cause mortality rate was 11.4% versus 0% (p = 0.109), respectively.
      Conclusions: The 2-year results revealed higher safety, superior efficacy, and
      greater clinical benefits of DESs than BMSs for treating TASC-II B SFA occlusive
      disease. However, more cases and long-term follow-up are warranted.

PMID- 29643699
TI  - Clinical Efficacy of Transthoracic Echocardiography for Screening Abdominal
      Aortic Aneurysm in Turkish Patients.
AB  - Background: The objective of this study was to investigate the prevalence of
      abdominal aortic aneurysm (AAA) in Turkish patients aged >= 65 years, and to
      demonstrate the applicability of echocardiography to AAA screening. Methods:
      Transthoracic echocardiography (TTE) was performed in all consecutive patients
      aged >= 65 years who were referred to cardiology clinics or were referred from
      other outpatient clinics. The abdominal aorta (AA) of each patient was scanned
      using the same probe, and the time spent was recorded. Demographic and clinic
      characteristics of the patients were recorded at the end of the echocardiography.
      Results: Among 1948 patients (mean age 70.9 +/- 6 years; 49.8% male), the AA was
      visualized in 96.3%. AAA was identified in 3.7% (69/1878) of the patients, of
      whom AAA was previously known in 20.3% (n = 14). The prevalence of unknown AAA
      was 2.93%. The average time needed to scan and measure the AA was 1 minute and 3
      seconds (+/-23 seconds). Aortic root diameters were significantly higher in the
      patients with AAA than in those without AAA (34.7 +/- 4.2 vs. 29.8 +/- 4.7; p <
      0.001). Age (per 1 year increase) [odds ratio (OR), 1.245; p < 0.001], male
      gender (OR, 5.382; p < 0.001), smoking (OR, 2.118; p = 0.037), and aortic root
      diameter (per 1 mm increase) (OR, 1.299; p < 0.001) were independent predictors
      of AAA. Conclusions: This study is important in that it showed a high prevalence
      of AAA in Turkish patients aged >= 65 years, and demonstrated that AAA can be
      visualized in the majority of patients in as little as 1 minute during TTE.

PMID- 29643700
TI  - Evaluation of the Accuracy of ECG Captured by CardioChip through Comparison of
      Lead I Recording to a Standard 12-Lead ECG Recording Device.
AB  - Background: Remote cardiac rhythm monitoring and recording, using hand-carried
      electrocardiogram (ECG) device had been widely used in telemedicine. The
      feasibility and accuracy analysis on the data recorded by a new miniature ECG
      system-on-chip (SoC) system has not been explored before. Methods: This study
      evaluated the accuracy of the ECG recordings captured by CardioChip - a single
      channeled, low-powered, miniature ECG SoC designed for mobile applications;
      comparing against Philips Pagewriter Trim III - a Food and Drug Administration
      certified, widely-used standard 12-lead ECG recording device, within Mackay
      Memorial Hospital in Taiwan. Results: Total of 111 participants, age ranging from
      39 to 87years old [mean age: 61.2 +/- 13.4, 57 male (51.3%)] were enrolled. Two
      experienced cardiologists rated and scored the ECG morphology to be the same
      between the two devices, while CardioChip ECG was more sensitive to baseline
      noise. R-peak amplitudes measured both devices using single lead information
      (CardioChip ECG vs. Lead 1 in standard 12-lead ECG) showed statistical
      consistency. Offline analysis of signal correlation coefficients and coherence
      showed good correlation with both over 0.94 in average (0.94 +/- 0.04 and 0.95 +/
      0.04, respectively), high agreement between raters (94% agreement) for detecting
      abnormal cardiac rhythm with excellent R-peak amplitude (r = 0.98, p < 0.001) and
      PR interval (r = 0.91, p < 0.001) correlations, indicating excellent correlation
      between ECG recordings derived from two different modalities. Conclusions: The
      results suggested that CardioChip ECG is comparable to medical industry standard
      ECG. The future implementation of wearable ECG device embedded with miniature ECG
      system-on-chip (SoC) system is ready for clinical use, which will potentially
      enhance efficacy on identifying subjects with suspected cardiac arrhythmias.

PMID- 29643701
TI  - Higher Ventricular Premature Complex Burden is Associated with Lower Systolic
      Blood Pressure Response.
AB  - Background: Ventricular premature complexes (VPCs) with a burden higher than 10%
      to 20% of total daily heart beats can cause VPC-induced cardiomyopathy. The
      systolic blood pressure response (SBPR) is the difference between the SBP during
      maximal exercise and rest. A low SBPR was recently identified to be a marker of
      cardiomyopathy. The aim of this manuscript was to clarify the association between
      VPC burden and SBPR. Methods: From January to December 2015, all patients with a
      VPC burden larger than 240 beats/day on Holter recordings and treadmill exercise
      tests were enrolled. The patients with a heart rhythm other than sinus rhythm,
      coronary artery disease, and severe cardiomyopathy were excluded. The SBPR was
      measured during a treadmill test. The basic characteristics and echocardiographic
      findings were collected. Results: All patients were classified into three groups:
      Group 1; 240-1,000 VPCs/day (n = 78), Group 2; 1,000-10,000 VPCs/day (n = 54),
      and Group 3; > 10,000 VPCs/day (n = 21). Group 1 had a higher SBPR than the other
      groups. Multivariate analysis revealed that only VPC burden was associated with
      SBPR. Receiver operating characteristic curve analysis showed that a VPC burden >
      1,055 beats/day predicted a SBPR < 40 mmHg. The results were consistent in all
      subgroups. There were no significant differences in echocardiographic findings
      among the groups. Conclusions: AVPC burden higher than 1,055 beats/day was
      associated with a reduced SBPR.

PMID- 29643702
TI  - Evaluation of Right Ventricular Function by Speckle-Tracking Echocardiography in
      Patients with Ankylosing Spondylitis: A Case-Control Study.
AB  - Background: We aimed to evaluate the right ventricular (RV) systolic function in
      patients with ankylosing spondylitis (AS) compared to healthy subjects by using
      standard echocardiography and speckle-tracking echocardiography (STE) methods.
      Methods: This was a case-control study in which 64 patients (mean age, 55.7 +/-
      9.2 years; male/female, 53/11), who had AS for at least five years (mean disease
      duration, 7.1 +/- 2.6 years) and 70 age-matched healthy subjects (mean age, 54.9
      +/- 8.5 years; male/female 55/15) were included. Clinical and laboratory signs of
      cardiac disease were recorded. The RV systolic function was assessed by standard
      echocardiography and two-dimensional STE method. Results: Case and control groups
      did not show significant difference in terms of clinical and laboratory signs of
      cardiac disease. RV function parameters in standard echocardiography were
      statistically similar between AS patients and control subjects. However, RV
      parameters in STE revealed significantly impaired RV function in AS patients
      compared to control group. RV-free wall longitudinal strain, RV-free wall
      longitudinal systolic strain rate, RV-free wall longitudinal early diastolic
      strain rate, RV-free wall longitudinal late diastolic strain rate were lower, and
      RV-early diastolic strain rate/RV-late diastolic strain rate ratio was higher for
      the patients in the AS group (p < 0.001 for all). Conclusions: AS is associated
      with impaired RV function as shown by STE even if there is no clinical or
      laboratory sign of cardiac abnormality. STE is more effective than standard
      echocardiography to detect RV function. Therefore we suggest regular evaluation
      of RV function in patients with AS.

PMID- 29643703
TI  - Associations of Ambient Temperature with Mortality Rates of Cardiovascular and
      Respiratory Diseases in Taiwan: A Subtropical Country.
AB  - Background: We conducted a time-series analysis of daily ambient temperature and
      all-cause, cardiovascular, and respiratory disease mortality in Taiwan, which is
      generally neither extremely hot nor cold. Methods: Data on all-cause daily
      mortality rates (excluding accidents, suicide, and homicide), and mortality rates
      due to respiratory and cardiovascular diseases between 2008 and 2010 were
      obtained from the Taiwan Death Registry. The daily temperature for that period
      was averaged from 33 monitoring stations nationwide. A generalized least square
      model was constructed to assess the relationship between the time-series trends
      of temperature and mortality, and the cross-correlation function was used to
      determine the possible time lag for the effect of temperature on mortality.
      Results: As the average temperature increased, the daily all-cause (beta = 
      0.006) and respiratory disease (beta = -0.012) mortality rates decreased. On the
      other hand, an inverse relationship (beta = -0.028) between average daily
      temperature and cardiovascular disease mortality was observed only for a
      temperature between 12.91  degrees C and 26.36  degrees C. The time lag for all
      cause and cardiovascular disease mortality was similar at 4-6 days, while the lag
      for respiratory disease was longer at 13-16 days. Conclusions: We found inverse
      associations between average temperature and all-cause and respiratory mortality.
      An inverse association between temperature and cardiovascular disease mortality
      was observed only from 12.91  degrees C to 26.36  degrees C.

PMID- 29643704
TI  - Bioinformatic Analysis of the Possible Regulative Network of miR-30a/e in
      Cardiomyocytes 2 Days Post Myocardial Infarction.
AB  - Background: Both miR-30a and miR-30e are significantly downregulated in
      cardiomyocytes (CMs) 2 days (d) post myocardial infarction (MI). This study aimed
      to identify their possible regulative network in CMs 2d post-MI. Methods: The
      dysregulated mRNAs in left ventricle tissues 2d post-MI in mice model were
      retrieved from one previous publication. The verified target genes of miR-30a/e
      and the predicted targets (upregulated 2d post-MI) were subjected to analysis of
      the involvement in biological processes according to their enrichment in gene
      ontology (GO) terms. Results: The known targets of miR-30a/e can regulate
      cellular responses to glucose starvation via targeting TP53, BECH1 and HSPA5, and
      also control cardiac epithelial to mesenchymal transition via targeting ETS
      related gene (ERG), SNAI1 and NOTCH1. Bioinformatic prediction further showed
      that miR-30a might regulate some biological processes related to CM responses to
      MI via some other potential targets, such as platelet aggregation (possibly via
      ITGB3 and STXBP1), regulation of intrinsic apoptotic signaling pathway in
      response to deoxyribonucleic acid damage (possibly via SNAI1) and positive
      regulation of tyrosine phosphorylation of Stat3 protein (possibly via LYN, SOCS3
      and SLCF1). Conclusions: Considering the importance of these genes in cellular
      responses to MI, it is meaningful to further investigate the regulative effect of
      miR-30a/e on their expression, as well as their regulative network in CMs.

PMID- 29643705
TI  - Amiodarone for the Successful Management of Caowu Poisoning - Induced Cardiac
      Arrhythmia.

PMID- 29643706
TI  - Insomnia and Atrial Fibrillation: Risk Assessment.

PMID- 29643707
TI  - Insomnia and the Risk of Atrial Fibrillation: A Population-Based Cohort Study.

PMID- 29643708
TI  - Evidence-based review and appraisal of the use of droperidol in the emergency
      department.
AB  - Droperidol is a short-acting, potent dopamine D2 antagonist that can pass through
      the blood-brain barrier. A black box warning was issued for droperidol by the
      United States Food and Drug Administration in 2001 because of a risk of
      development of torsades de pointes induced by QT prolongation. Many experts feel
      that the incidence of arrhythmia is overestimated, and low-dose droperidol is
      almost always used by anesthesiologists for postoperative nausea and vomiting. In
      this review, we used evidence-based analysis to appraise high-quality studies
      with a low risk of bias published after 2001 on the use of droperidol in the
      emergency department (ED). Droperidol appears not only efficacious but also safe
      to treat patients with nausea/vomiting, acute psychosis, and migraine in the ED.
      For these conditions, droperidol may be an option for shared decision-making.

PMID- 29643709
TI  - Delayed formation of hematomas with ethanol preconditioning in experimental
      intracerebral hemorrhage rats.
AB  - Objective: Spontaneous intracerebral hemorrhage (ICH) accounts for 10%-15% of all
      strokes and causes high mortality and morbidity. In the previous study, we
      demonstrated that ethanol could aggravate the severity of brain injury after ICH
      by increasing neuroinflammation and oxidative stress. In this study, we further
      investigate the acute effects of ethanol on brain injury within 24 h after ICH.
      Materials and Methods: Totally, 66 male Sprague-Dawley rats were assigned
      randomly into two groups: saline pretreatment before ICH (saline + ICH), and
      ethanol pretreatment before ICH (ethanol + ICH). Normal saline (10 mL/kg) or
      ethanol (3 g/kg, in 10 mL/kg normal saline) was administered intraperitoneally 1
      h before induction of experimental ICH. Bacterial collagenase VII-S (0.23 U in
      1.0 MUL sterile saline) was injected into the right striatum to induce ICH in the
      rats. We evaluated the hematoma expansion, hemodynamic parameters (heart rate and
      blood pressure), activated partial thromboplastin time (aPTT), prothrombin time
      (PT), and striatal matrix metallopeptidase 9 (MMP-9) expressions at 3, 6, 9, and
      24 h after ICH. Results: The ethanol + ICH group exhibited decreased hematoma at
      3 h after ICH; nevertheless, there was a larger hematoma compared with the saline
      + ICH group at 9 and 24 h after ICH. The ethanol + ICH group had lower blood
      pressure at 3, 6, and 9 h post-ICH, but both groups maintained similar heart
      rates after ICH. There was no significant difference in the aPTT and PT between
      the two groups. Incremental ethanol concentrations had no influence on
      collagenase VII-S activity at 120 min in vitro. MMP-9 expression was upregulated
      in the right striata of the ethanol + ICH group, especially at 3 and 9 h after
      ICH. Conclusion: Ethanol delayed hematoma formation in the first 3 h due to a
      hypotensive effect; however, the accelerated growth of hematomas after 9 h may be
      a sequela of ethanol-induced MMP-9 activation.

PMID- 29643710
TI  - Positive correlation of serum leptin levels and peripheral arterial stiffness in
      patients with type 2 diabetes.
AB  - Objective: Leptin plays a pathophysiologic role in the pathogenesis of aortic
      dysfunction and peripheral arterial stiffness (PAS). Our aim was to evaluate the
      risk factors for developing PAS and the association of leptin and PAS in patients
      with type 2 diabetes mellitus (DM). Materials and Methods: Fasting blood samples
      were obtained for biochemical data and leptin determinations from 105 patients
      with type 2 DM. In this study, we applied an automatic pulse wave analyzer
      (VaSera VS-1000) to measure the brachial-ankle pulse wave velocity (baPWV); a
      baPWV value >14.0 m/s on either side was considered high PAS. Results: Seventy
      five patients (71.4%) had high PAS and they included a higher percentage of
      patients with hypertension (P < 0.001), older age (P < 0.001), and a higher body
      fat mass (P = 0.043), systolic blood pressure (P < 0.001), diastolic blood
      pressure (P = 0.016), serum blood urea nitrogen (P = 0.003), and leptin level (P
      < 0.001), and lower height (P = 0.027) and glomerular filtration rate (P < 0.001)
      compared with type 2 DM patients with low PAS. After adjusting for factors
      significantly associated with PAS in these patients by multivariate logistic
      regression analysis, age (beta = 0.470, adjusted R2 change = 0.279; P < 0.001),
      logarithmically transformed leptin (log-leptin, beta = 0.259, adjusted R2 change
      = 0.085; P = 0.001), and hypertension (beta = 0.197, adjusted R2 change = 0.031;
      P = 0.011) were significant independent predictors of PAS in type 2 DM patients.
      Conclusion: The serum leptin level could be a predictor of PAS in type 2 DM
      patients.

PMID- 29643711
TI  - Dental utilization and expenditures by children and adolescents with autism
      spectrum disorders: A population-based cohort study.
AB  - Objectives: It is understood that children and adolescents with autism spectrum
      disorders (ASDs) have difficulty in receiving dental treatment. This study
      explores the differences in dental utilization and expenditure between two
      groups: children and adolescents with and without ASD. Different conditions that
      affect these results will be examined, including area of residence, category of
      treatment, and preferences concerning type of dental institution in Taiwan.
      Materials and Methods: The health service research database of the National
      Health Research Institutes, which features population-based, randomly selected
      samples collected from 2001 to 2010, was utilized in this study. In particular,
      we recruited samples from 2005 in accordance with the codes of the International
      Classification of Diseases, 9th revision, Clinical Modification from 299.0 to
      299.9. The population-based cohort study measured mean expenditures and mean
      numbers of medical visits with regard to different dental institution
      classifications, areas of residence, and categories of dental treatment for
      children (under 18 years old) with and without ASD. Results: The mean number of
      annual visits was 6.58 and 5.70 for children and adolescents with and without
      ASD, respectively, with mean annual visit expenditures of NT$2401.20 and
      NT$1817.99, respectively. A higher percentage of children (91.32%) and
      adolescents (72.66%) with ASD had experienced dental treatment than those without
      ASD. Children (93.23%) and adolescents (90.83%) without ASD visited dental
      clinics more often than those with ASD. The percentage of dental visits to
      academic medical centers in Eastern Taiwan was significantly lower for the ASD
      group than visits to other types of dental institutions. The use of restorative
      treatment was significantly higher among all samples, with periodontology having
      the lowest percentage. Conclusions: Children and adolescents with ASD had greater
      dental utilization, expenditures, and preferences for high-level dental
      institutions. The discrepancies in dental utilization indicate differences in the
      distribution of medical resources in different dental institution levels and
      residence areas in Taiwan.

PMID- 29643712
TI  - Surgical results of a one-stage combined anterior lumbosacral fusion and
      posterior percutaneous pedicle screw fixation.
AB  - Objectives: Lumbosacral fusion through either an anterior or a posterior approach
      to achieve good lordosis and stability is always a challenging surgical operation
      and is often accompanied by a higher rate of pseudarthrosis than when other
      lumbar segments are involved. This study evaluated the clinical and radiological
      results of lumbosacral fusions achieved through a combined anterior and posterior
      approach. Materials and Methods: From June 2008 to 2012, 20 patients who had L5
      S1 instability and stenosis were consecutively treated, first by anterior
      interbody fusion using an allogenous strut bone graft through the pararectus
      approach and then by posterior pedicle screw fixation. A minimum of 1-year of
      clinical and radiological follow-up was conducted. Intraoperative blood loss,
      surgical time, and any surgery-related complications were recorded. Clinical
      outcomes were assessed using a visual analog scale (VAS) and the patient's
      Oswestry Disability Index (ODI) score. After 1 year, radiological outcomes were
      assessed by analyzing pelvic incidence, lumbar lordosis, and segmental lordosis
      using static plain films, while fusion stability was assessed using dynamic plain
      films. Results: The mean operative time and blood loss were 215 min and 325 cc,
      respectively. After 1 year, the VAS and ODI scores had significantly improved,
      and stable fusion with good lordotic curvature was obtained in all cases.
      Conclusion: The surgical results of the combined procedure are satisfactory in
      terms of the functional and radiological outcomes. Our method offers advantages
      regarding both anterior fusion and posterior fixation.

PMID- 29643713
TI  - Modified conjunctival flap as a primary procedure for nontraumatic acute corneal
      perforation.
AB  - Objective: Appropriate management of nontraumatic acute corneal perforation is
      always a challenge even with the many advances in surgical materials and
      techniques. We reported the outcomes of a case series of acute corneal
      perforation repair using a newly modified conjunctival flap with amniotic
      membrane transplant (AMT), fibrin glue, and a bandage soft contact lens (BCL).
      Materials and Methods: A total of 13 consecutive referral cases with nontraumatic
      acute corneal perforation at the University of Washington were reviewed. All open
      globes were repaired by a combined surgery with a modified conjunctival flap,
      AMT, fibrin glue, and BCL. Visual acuity, a slit lamp examination, and the
      patient-reported pain level were collected preoperatively and postoperatively.
      Subsequent corneal surgeries to improve visual function were also reviewed.
      Results: All ocular surfaces of the 13 eyes were stable at postoperative follow
      up. Eleven of the 13 patients had the same or worse visual acuity 1 week
      postoperatively. Nine of the 13 patients achieved better vision 6 months
      postoperatively. None of the patients developed perioperative or postoperative
      complications. Five patients with good visual potential underwent further corneal
      surgeries, including Boston keratoprosthesis and penetrating keratoplasty. The
      average referral distance was 217 miles and the median number of follow-up visits
      within 6 months was 4. Conclusions: The combination of a modified conjunctival
      flap, AMT, fibrin glue, and a BCL could provide a temporary method to stabilize
      and secure the integrity of the globe as well as the ocular surface after a
      nontraumatic acute corneal perforation. This approach allows easy follow-up and
      preserves the eye for future corneal surgery under optimal conditions.

PMID- 29643715
TI  - Effectiveness of a training program on the role recognition and case portrayal of
      standardized patients.
AB  - Objective: Standardized patient (SP) scenarios could provide medical situations
      of high fidelity for teaching or examinations, which would otherwise be difficult
      with real patients. Moreover, SPs can also be used to reliably evaluate or
      certify the competence of medical trainees. Since the interactions between
      examinee and SP are dynamic and complex, SPs need to portray the case reliably
      and consistently across different examinees. Thus, we developed a 1-day program
      for newly recruited SPs to teach basic competence in case portrayal. The purpose
      of this study is to assure the effectiveness of this training program in role
      recognition as a SP and case portrayal. Materials and Methods: A total of 80 SPs
      were recruited from 2010 to 2013. They were asked to complete questionnaires
      before and after the training program using a five-point, Likert-type scale (1 -
      strongly disagree and 5 - strongly agree). The questionnaire comprised 16 items
      covering SP characteristics, role recognition, and case portrayal. The results
      were analyzed using PASW Statistics 18, paired t-test, to determine the
      effectiveness of the training program. Results: A total of 78 questionnaires were
      collected for a response rate of 97.5%. The mean age of the SPs was 50.2 +/- 7.9
      (25-68) years. Most SPs showed improvement in role recognition. In the domain of
      case portrayal, three of nine items (consistency, obedience, and commitment)
      showed significant difference (P <0.05). Conclusions: This study suggests that
      this program is useful for reinforcing role recognition in newly recruited SPs.
      With respect to case portrayal, only consistency, obedience, and commitment were
      improved.

PMID- 29643714
TI  - Combined effect of acid-sensing ion channel 3 and transient receptor potential
      vanilloid 1 gene polymorphisms on blood pressure variations in Taiwanese.
AB  - Objectives: Both acid-sensing ion channel acid-sensing ion channel 3 (ASIC3) and
      transient receptor potential vanilloid 1 (TRPV1) have been proposed to be
      involved in the pathophysiology of hypertension. Common colocalization of ASIC3
      and TRPV1 channels in the same sensory neuron has been reported. We aimed to
      study the combined ASIC3 and TRPV1 gene polymorphisms in the risk of
      hypertension. Materials and Methods: To test the statistical association between
      genetic polymorphisms of the ASIC3 and TRPV1 genes and blood pressure (BP)
      variations in Taiwanese, 551 unrelated individuals (286 men and 265 women) having
      routine health examinations were recruited. The participants had no history of
      cardiovascular disease or use of medication for hypertension. Results: Six ASIC3
      and four TRPV1 gene polymorphisms were genotyped, and only the ASIC3 rs2288646
      polymorphism was associated with variations in BP in the participants. In
      subgroup analysis, we found participants carrying the combined ASIC3 rs2288646 AA
      or AG and TRPV1 rs8065080 CC genotypes (combined genotypes) had significantly
      higher systolic, mean and diastolic BP compared with the other subgroups (P =
      0.009, 0.003, and 0.006, respectively, after Bonferroni correction). Interaction
      analysis also revealed significant gene-gene interaction in the systolic, mean,
      and diastolic BP in the ASIC3 and TRPV1 genotypes (interaction P = 0.006, 0.002,
      and 0.002, respectively). A trend of increasing frequencies of the combined
      genotype was observed in normotensive, prehypertensive, and hypertensive
      subgroups (P for trend = 0.001), as well as in those with higher systolic and
      diastolic BPs (P for trend = 9.13 * 10-4 and P for trend = 5.5 * 10-5,
      respectively). Conclusion: Our data show a combined effect of ASIC3 and TRPV1
      gene polymorphisms in BP variations in Taiwanese. These results suggest that the
      interaction between ASIC3 and TRPV1 is involved in BP regulation.

PMID- 29643716
TI  - Brain metastasis from renal urothelial carcinoma successfully treated by
      metastasectomy.
AB  - Upper tract urothelial cancer (UTUC) arises from the urothelial lining of the
      urinary tract. UTUC spreads in several different ways including direct invasion,
      lymphatic spread, and hematogeneous metastases. Regional lymph nodes are commonly
      the initial site of metastasis, followed by the liver, lung, and bone. Brain
      metastasis is uncommon in patients with urothelial carcinoma. Here, we report an
      uncommon case of kidney urothelial carcinoma with brain metastasis in a 55-year
      old woman presenting with dysarthria with right side limb weakness. The patient
      recovered well after resection of the brain lesion without any sequelae after 1
      year of follow-up.

PMID- 29643717
TI  - Penile and multiple cutaneous metastases over the pubic region from a rectal
      adenocarcinoma: An uncommon case.
AB  - Synchronous penile and multiple cutaneous metastases over the pubic region from a
      rectal adenocarcinoma are rare, and they usually indicate widespread disease. The
      most frequent localization of cutaneous metastases is the postoperative scar.
      Simultaneous penile and pubic region metastases are extremely uncommon. Although
      a penile metastasis from a rectal adenocarcinoma has been reported, synchronous
      metastases over the penile and pubic area have not been reported previously. We
      present a case of penile and multiple cutaneous metastases over the pubic region
      from a rectal adenocarcinoma along with a brief review of the literature. To the
      best of our knowledge, this is the first such case reported to present with
      simultaneous penile and multiple cutaneous metastases.

PMID- 29643719
TI  - Glomus tumor with rare clinical presentation as chronic shoulder pain.

PMID- 29643718
TI  - Left-sided cecal diverticulitis associated with midgut malrotation.
AB  - Malrotation of the midgut is generally considered as a pediatric pathology with
      the majority of patients presenting in childhood. The diagnosis is rare in
      adults, which sometimes leads to delay in diagnosis and treatment. An index of
      suspicion is therefore required when dealing with patients of any age group with
      abdominal symptoms. We present a case of a 26-year-old male who presented with
      left lower abdominal pain with preoperative computed tomography showing suspected
      left-sided appendicitis associated with midgut malrotation. The duodenum, small
      bowel, and cecum were abnormally located, with the presence of a thickened and
      inflamed appendix with fecalith images. The patient underwent an emergency
      laparotomy, and ruptured cecal diverticulitis with abscess formation was
      confirmed. We performed a cecectomy, and the patient did not have an uneventful
      postoperative recovery. A review of the literature is presented to highlight the
      rarity of midgut malrotation and the controversies surrounding its surgical
      management in the adult population with ruptured left-sided cecal diverticulitis.

PMID- 29643720
TI  - Anthropological and sociological perspectives of medical professionalism.

PMID- 29643721
TI  - Scalable Bayesian Variable Selection Using Nonlocal Prior Densities in Ultrahigh
      dimensional Settings.
AB  - Bayesian model selection procedures based on nonlocal alternative prior densities
      are extended to ultrahigh dimensional settings and compared to other variable
      selection procedures using precision-recall curves. Variable selection procedures
      included in these comparisons include methods based on g-priors, reciprocal
      lasso, adaptive lasso, scad, and minimax concave penalty criteria. The use of
      precision-recall curves eliminates the sensitivity of our conclusions to the
      choice of tuning parameters. We find that Bayesian variable selection procedures
      based on nonlocal priors are competitive to all other procedures in a range of
      simulation scenarios, and we subsequently explain this favorable performance
      through a theoretical examination of their consistency properties. When certain
      regularity conditions apply, we demonstrate that the nonlocal procedures are
      consistent for linear models even when the number of covariates p increases sub
      exponentially with the sample size n. A model selection procedure based on
      Zellner's g-prior is also found to be competitive with penalized likelihood
      methods in identifying the true model, but the posterior distribution on the
      model space induced by this method is much more dispersed than the posterior
      distribution induced on the model space by the nonlocal prior methods. We
      investigate the asymptotic form of the marginal likelihood based on the nonlocal
      priors and show that it attains a unique term that cannot be derived from the
      other Bayesian model selection procedures. We also propose a scalable and
      efficient algorithm called Simplified Shotgun Stochastic Search with Screening
      (S5) to explore the enormous model space, and we show that S5 dramatically
      reduces the computing time without losing the capacity to search the interesting
      region in the model space, at least in the simulation settings considered. The S5
      algorithm is available in an R package BayesS5 on CRAN.

PMID- 29643722
TI  - Challenges in Diagnosing Childhood Tuberculosis.

PMID- 29643723
TI  - Text Comprehension and Oral Language as Predictors of Word-Problem Solving:
      Insights into Word-Problem Solving as a Form of Text Comprehension.
AB  - This study was designed to deepen insights on whether word-problem (WP) solving
      is a form of text comprehension (TC) and on the role of language in WPs. A sample
      of 325 second graders, representing high, average, and low reading and math
      performance, was assessed on (a) start-of-year TC, WP skill, language,
      nonlinguistic reasoning, working memory, and foundational skill (word
      identification, arithmetic) and (b) year-end WP solving, WP-language processing
      (understanding WP statements, without calculation demands), and calculations.
      Multivariate, multilevel path analysis, accounting for classroom and school
      effects, indicated that TC was a significant and comparably strong predictor of
      all outcomes. Start-of-year language was a significantly stronger predictor of
      both year-end WP outcomes than of calculations, whereas start-of-year arithmetic
      was a significantly stronger predictor of calculations than of either WP measure.
      Implications are discussed in terms of WP solving as a form of TC and a
      theoretically coordinated approach, focused on language, for addressing TC and WP
      solving instruction.

PMID- 29643725
TI  - Modified Laminoplasty for Degenerative Cervical Spondylosis: The Technique of
      Floating Laminoplasty.
AB  - Background: Laminoplasty is an established alternative to laminectomy for
      posterior cervical decompression in spondylotic myelopathy. However, standard
      laminoplasty requires internal fixation, which is often not obtainable in
      developing countries. We present our experience with a technique of
      noninstrumented (floating) laminoplasty developed to avoid the need to anchor the
      laminoplasty to the anterior elements. Methods: We have used floating
      laminoplasty (FL) for posterior cervical decompression in patients with cervical
      spondylosis since 2004 and report the technique and our experience with it
      between 2009 and 2014 when C-arm and magnetic resonance imaging became available
      in our unit. Patients who had classical laminectomy and hemilaminectomies were
      excluded. The operation involved bilateral approach to the laminae through a
      midline incision with generous sparing of the supraspinous, interspinal and
      interlaminar ligaments. During closure the laminoplasty was hitched to the
      ligamentum nuchae. Nurick grading was used for clinical evaluation. Patients were
      followed for at least 1 year. Results: There were 36 patients with age range
      between 32 and 72 years (mean: 56.5 years). Male to female ratio was 3:1. Most
      patients presented with advanced disease, with 25%, 36%, and 30% at Nurick Grade
      3, 4, and 5, respectively. Postoperatively, all (100%) patients with Nurick Grade
      2 and 3 improved to Grade 1 or 0, while 9 (69%) of the 13 at Grade 4 improved to
      Grade 2 or better. Only 1 (9.1%) of 11 operated at Grade 5 did not improve while
      3 (27%) improved to Grade 2 or better. No postoperative instability was
      identified on follow-up. Conclusion: FL is a safe and simple procedure that
      preserves spine stability and minimizes postoperative spinal deformity.

PMID- 29643726
TI  - Early Versus Delayed Oral Feeding after Uncomplicated Cesarean Section under
      Spinal Anesthesia: A Randomized Controlled Trial.
AB  - Objective: The objective of this study is to compare the safety of early versus
      delayed oral feeding after uncomplicated cesarean section (CS) under spinal
      anesthesia. Methods: This was a randomized, controlled trial that enrolled 152
      women who had uncomplicated CS under spinal anesthesia between January 2014 and
      June 2014. Women in the early feeding group had sips of oral fluid 6 h
      postoperatively while those in the delayed feeding group were on nil per oral for
      the first 24 h after surgery before commencement on liquid diet. Primary outcome
      measure was development of symptoms of paralytic ileus while secondary outcome
      measures included time interval to return of bowel sound, duration of hospital
      stay, and patients satisfaction which was determined using a visual analog score.
      Results: The incidence of mild ileus symptoms was similar in both groups. Early
      fed group had significantly shorter mean postoperative time intervals to return
      of bowel sound, (7.3 h vs. 11.5 h [P = 0.005]), passage of flatus, (30.7 h vs.
      37.5 h [P = 0.009]). Hospital stay was also significantly shorter in the early
      feeding group, (4.2 days vs. 4.9 days [P < 0.001]). Early-fed women had higher
      levels of satisfaction. Conclusion: Early initiation of oral feeding after
      uncomplicated CS under subarachnoid block is not associated with increased
      incidence of gastrointestinal symptoms or paralytic ileus.

PMID- 29643724
TI  - Resolvin D1 promotes corneal epithelial wound healing and restoration of
      mechanical sensation in diabetic mice.
AB  - Purpose: To investigate the effect and mechanism of proresolving lipid mediator
      resolvin D1 (RvD1) on the corneal epithelium and the restoration of mechanical
      sensation in diabetic mice. Methods: Type 1 diabetes was induced in mice with
      intraperitoneal streptozocin injections. The healthy and diabetic mice underwent
      removal of the central corneal epithelium, and then 100 ng/ml RvD1 or its formyl
      peptide receptor 2 (FPR2) antagonist WRW4 was used to treat the diabetic mice.
      Regeneration of the corneal epithelium and nerves was observed with sodium
      fluorescein staining and whole-mount anti-beta3-tubulin fluorescence staining.
      The inflammatory response level was measured with hematoxylin and eosin staining
      (inflammatory cell infiltration), enzyme-linked immunosorbent assay (tumor
      necrosis factor alpha and interleukin-1 beta content), myeloperoxidase activity,
      and fluorescence staining (macrophage content). The reactive oxygen species (ROS)
      and glutathione (GSH) levels were examined with incubation with fluorescent
      probes, and oxidative stress-related protein expression levels were evaluated
      with fluorescence staining and western blotting. Results: Topical application of
      RvD1 promoted regeneration of the corneal epithelium in diabetic mice,
      accompanied by the reactivation of signaling and inflammation resolution related
      to regeneration of the epithelium. Furthermore, RvD1 directly attenuated the
      accumulation of ROS and nicotinamide adenine dinucleotide phosphate oxidase 2/4
      expression, while RvD1 enhanced GSH synthesis and reactivated the Nrf2-ARE
      signaling pathway that was impaired in the corneal epithelium in the diabetic
      mice. More interestingly, topical application of RvD1 promoted regeneration of
      corneal nerves and completely restored impaired mechanical sensitivity of the
      cornea in diabetic mice. In addition, the promotion of corneal epithelial wound
      healing by RvD1 in diabetic mice was abolished by its FPR2 antagonist WRW4.
      Conclusions: Topical application of RvD1 promotes corneal epithelial wound
      healing and the restoration of mechanical sensation in diabetic mice, which may
      be related to the lipid mediator's regulation of inflammation resolution, the
      reactivation of regenerative signaling in the epithelium, and the attenuation of
      oxidative stress.

PMID- 29643727
TI  - Outcome of Mainz II Pouch Urinary Diversion after Radical Cystectomy in Patients
      with Muscle-invasive Bladder Cancer: Our Experience.
AB  - Introduction: Mainz II pouch urinary diversion in patients with muscle-invasive
      bladder cancer is one of the options of continent urinary diversion following
      radical cystectomy (RC). We aim to report our experience and the outcome of our
      patients who had this procedure. Patients and Methods: Patients who had RC and
      Mainz II pouch urinary diversion for muscle-invasive bladder cancer in our
      institution from 2007 to 2016 were evaluated. Variables analyzed included age,
      gender, stage of the disease, pathological grade and tumor types, complications,
      and survival status. Results: There were 11 patients who had Mainz II pouch
      urinary diversion after RC for bladder cancer over a 10-year period. Four (36%)
      were male and 7 (64%) were female. The mean age of the patients was 58.6 (range,
      52-65) years. The diseases were pT2, pT3, and pT4 in 2 (18%), 7 (64%), and 2
      (18%) patients, respectively. Four (36%) had pelvic nodal metastasis. Nine (82%)
      had a histological diagnosis of transitional cell carcinoma, and two (18%) were
      squamous cell carcinoma (SCC). Ten (91%) patients had high-grade disease, whereas
      only 1 (9%) patient had low-grade disease. Short-term morbidities were
      electrolytes derangement, hypokalemia, and acidosis in 2 (18%) patients and
      pyelonephritis in 2 (18%) patient. The two patients with invasive SCC had
      recurrence and death within 12 months of surgery. At present, four of the
      patients are alive, and seven are dead. Survival till date ranged from 8 to 120
      months (mean survival time was 48 months). All patients achieved day and night
      time continence, and there was no significant long-term morbidity from the method
      of urinary diversion. Conclusion: Mainz II pouch urinary diversion is safe and
      acceptable to most of our patients with good long-term results.

PMID- 29643728
TI  - Use of Otoscope as a Diagnostic and Therapeutic Aid in Umbilical Pilonidal Sinus:
      A Novel Technique.
AB  - Introduction: Umbilical disorders are frequently encountered in general surgical
      practice. Although the sacrococcygeal region is the most common site for
      pilonidal sinus disease, it can be seen occasionally in periumbilical area.
      Treatment is mostly conservative for umbilical pilonidal sinus in contrast to the
      sacrococcygeal sinus where it is always surgical. In the era of endoscopy and
      minimally invasive surgery, we describe the use of otoscope as a novel technique
      for the diagnosis and treatment of umbilical pilonidal sinus. Subject and Method:
      In this prospective study, patients with a clinical suspicion of umbilical
      pilonidal sinus were included and diagnosis was confirmed on the basis of
      otoscopic finding. All patients were planned for conservative management i.e.
      extraction of hair fragments with the help of an otoscope followed by oral
      antibiotics treatment. On follow-up, response of treatment was noted by
      evaluation of symptoms and otoscopic examination. Result: Total 15 patients were
      included in this study. By using otoscope for removal of hair fragments from
      umbilical sinus, we found successful result in all patients with conservative
      treatment. Discussion: In umbilical pilonidal sinus, the success of conservative
      treatment depends on the effective extraction of hair and maintenance of personal
      hygiene by the patient. Our study showed 100% successful result of conservative
      treatment, probably due to proper and complete extraction of hair fragment with
      the help of the otoscope. Conclusion: Otoscopic examination and hair extraction
      for umbilical pilonidal sinus is a simple, cost-effective, and easy treatment
      that can be done in the outpatient department and does not require any formal
      training for its use.

PMID- 29643729
TI  - Resterilized Polypropylene Mesh for Inguinal Hernia Repair.
AB  - Purpose: The use of prosthetic biomaterials for reconstructing and reinforcing
      the posterior wall of the inguinal canal reduces the incidence of hernia
      recurrence. Cost, availability of mesh, and perhaps reluctance to adopt a new
      technique are factors which prevent widespread practice of hernioplasty in low
      resource settings. Use of resterilized mesh significantly reduces the cost of
      hernioplasty and is safe. Patients and Methods: Sheets of 30 cm * 30 cm
      polypropylene mesh were cut into 16 cm * 8 cm to produce mesh strips which were
      repackaged into SELFSEAL(r) (Medical Action Industries Inc., USA) sterilizing
      pouches measuring 90 mm * 230 mm and autoclaved. At repair, the strips are shaped
      to fit the anatomy of the posterior wall of the inguinal canal, a slit created at
      one end and applied in Lichtenstein repair of inguinal hernias. Patients were
      monitored for seroma collection and wound infection up to 2 weeks postoperative
      period. Results: Sixty inguinal hernia repairs were done in 58 patients using the
      resterilized mesh; two cases being bilateral. One patient (1.7%) had seroma
      collection at 2 weeks which was aseptically aspirated. We did not record any case
      of wound infection. Conclusion: The use of sterilized polypropylene mesh for the
      repair of inguinal hernias is safe and reduced the cost of hernioplasty by
      reducing the cost of polypropylene mesh. This technique is recommended in low
      resource settings.

PMID- 29643730
TI  - Transient Femoral Nerve Palsy Following Ilioinguinal Nerve Block for Inguinal
      Hernioplasty.
AB  - Background: Elective inguinal hernia repair in young fit patients is preferably
      done under ilioinguinal nerve block anesthesia in the ambulatory setting to
      improve throughput, save cost, and increase patient satisfaction. A rare
      complication of ilioinguinal nerve block is transient femoral nerve palsy (TFNP).
      Objectives: The aim of this study is to examine the incidence of TFNP among
      adults undergoing ambulatory inguinal hernia repair under ilioinguinal nerve
      block. Patients and Methods: Patients 18 years and older in the American Society
      of Anesthetists classes I and II who underwent ambulatory inguinal hernia repair
      over a 3-year period under ilioinguinal nerve block only were assessed for
      evidence of TFNP. All patients had power on the ipsilateral limb checked 30 min
      before and 1 h after the procedure. TFNP was considered present if there was
      sensory loss over the anterior aspect of the thigh, weakness of extension at the
      knee joint, or reduction in power of the ipsilateral limb. Results: One hundred
      and twelve patients were involved in the study; 90 (80.3%) males and 22 (19.6%)
      females with the mean age of 45.7 years. All had normal power (Grade 5) in the
      ipsilateral limb before instituting the nerve block. Postoperatively, 3 (2.6%)
      patients had grade 4 and recovered normal power over a 2-6-h period and were
      subsequently discharged. Conclusion: TFNP is a rare complication of ilioinguinal
      nerve block which delays patient discharge postambulatory hernioplasty.

PMID- 29643732
TI  - Cutaneous Cancers in Nigerian Albinos: A Review of 22 Cases.
AB  - Context: Albinism is an inherited disorder of hypopigmentation involving the
      skin, eyes, and hair. This disorder results in the absence or reduction in
      melanin production. There are two main types of albinism which are ocular
      albinism and oculocutaneous albinism. It could also be classified as syndromic or
      nonsyndromic the melanin, which protects from the harmful effect of ultraviolet
      radiation of the sun on the normal skin, is deficient in the albino, predisposing
      them more, to cutaneous malignancies. Aim: This study is to highlight the
      epidemiology of cutaneous cancers in albinos in sub-urban Nigeria. Methodology:
      This is a retrospective review of all albinos with histological diagnoses of
      cutaneous malignancies that presented to Irrua Specialist Teaching Hospital,
      Irrua Edo State, Nigeria between September 2010 and August 2016. The following
      details were extracted from the patients' case-notes, operation register, and the
      histopathology register. These data include age, gender, site of the lesion, the
      diagnosis, no of lesions excised, and duration of the lesion (s). These were
      collated and analyzed using SPSS version 22. Results: There were 22 albinos with
      histopathologically diagnosed cutaneous malignancies. There were 11 males and 11
      females with male:female of 1. The age range is from 25 to 55 years with the mean
      of 34.68. Conclusion: Albinism is one of the most common causes of cutaneous
      malignancies, and majority of them present with locally advanced lesions that
      will need excision biopsy resulting in disfigurement. This problem can be
      prevented in many cases with proper community education, support, and free health
      care. There is also need for them to present early whenever they noticed any skin
      changes.

PMID- 29643731
TI  - Childhood Pyogenic Osteomyelitis in Abakaliki, South East Nigeria.
AB  - Background: Pyogenic osteomyelitis is an important child health problem in
      developing countries. It is a one-disease state with a spectrum of pathological
      features and clinical forms ranging from acute to chronic presentation. Its
      pattern of presentation varies from and within subregions. The aim of this study
      was to determine the pattern and outcome of childhood pyogenic osteomyelitis in a
      low-resource environment. Materials and Methods: This was a retrospective study
      of all the children aged 18 years and under seen with pyogenic osteomyelitis in
      Federal Teaching Hospital Abakaliki between January 2005 and December 2015.
      Results: In 76 patients, there was pyogenic osteomyelitis involving 85 bones.
      Female-to-male ratio was 1:1.7, and the mean age was 9.9 +/- 5.1 years. The
      clinical forms of presentation were acute in 16 (21.1%), subacute in 10 (13.2%),
      and chronic in 50 (65.8%) patients. Acute osteomyelitis was the more likely form
      of presentation among infants (P < 0.001) and urban children (P < 0.011) whereas
      subacute and chronic osteomyelitis were more likely among the older children (P <
      0.001) and rural residents (P < 0.011). Staphylococcus aureus was the most common
      isolated pathogen. Anemia, septic arthritis, and pathological fractures were the
      three top complications observed. Fifty patients (65.8%) recovered and adjudged
      cured, 9 (11.8%) were lost to follow-up, and 17 (22.4%) were unable to afford the
      financial cost of the treatment. Conclusion: In our environment, chronic pyogenic
      osteomyelitis sequel to acute hematogenous bone infection in childhood is common.
      Poverty is also a limiting factor in its definitive treatment. These calls for a
      policy response aimed at improved care and preventive strategies based on the
      observed pattern.

PMID- 29643733
TI  - Camphor Burns on the Palm: An Unusual New Presentation.
AB  - Introduction: Camphor burns on the palm are uncommon and rarely encountered by a
      plastic surgeon. Aim: This study aims to analyze different patterns of camphor
      burns on the palm. Methods: Five women and one man presented with camphor burns
      on their palm. All patients had burns on their right palm. The shape of camphor,
      the duration of contact with the ignited camphor on the palm, and post-burn
      treatments were evaluated. Results: Three types of camphor burns were noted: Type
      1 (a ring-shaped or a dome-shaped blister with unburned skin in the center), Type
      2 (an oval-shaped partially thick burn with unburned skin in the center), and
      Type 3 (a full-thickness burn exposing the palmar fascia). Conclusion: Different
      types of camphor burns on the palm are described in this study. This is the first
      study to report ring-shaped blisters and ring-shaped partially thick camphor
      burns caused on the palm.

PMID- 29643734
TI  - Unusual Intravesical Foreign Body Following Perineo-vesical Injury.
AB  - Reports of foreign body in the bladder are rare. Various objects have been
      retrieved. Diagnosis is mainly by history of lower urinary tract symptoms and low
      abdominal pain combined with relevant radiological investigations. Treatment
      depends on the size, nature, and configuration of the object. The approach may be
      endoscopic or through open surgery depending on the above highlighted factors.

PMID- 29643735
TI  - Combined Laparoscopic and Cystoscopic Retrieval of Forgotten Translocated
      Intrauterine Contraceptive Device.
AB  - The most commonly used long-term reversible female contraception is intrauterine
      contraceptive device (IUCD). Its use is however associated with documented
      complications. Uterine perforation, though rare, is arguably the most surgically
      important of all these complications. We report a case of a 48-year-old para 4+0
      (4 alive) woman who had IUCD insertion 17 years earlier and had forgotten she had
      the device having had two children thereafter. The IUCD was subsequently
      translocated through the dome of the bladder into the peritoneal cavity with
      calculus formation around the tail and thread of the IUCD in the urinary bladder
      causing recurrent urinary tract infection. This "Collar Stud" effect made either
      cystoscopic or laparoscopic retrieval alone unsuccessful necessitating a combined
      approach. This case report highlights the need for a combined laparoscopic and
      cystoscopic approach in the retrieval of the unusual presentation of translocated
      IUCD.

PMID- 29643736
TI  - Desmoid Fibromatosis of the Lower Abdominal Wall in Irrua Nigeria.
AB  - Desmoid fibromatosis (desmoid tumors) is rare tumors. It can occur as intra
      abdominal, extraabdominal, or abdominal wall tumor depending on the site. The
      abdominal wall type is usually sporadic, but few have been associated with
      familial adenomatous polyposis. They are commonly seen in young females who are
      pregnant with a history of the previous cesarean section scar or within the 1st
      year of the last childbirth. There is an association between this tumor, presence
      of estrogen receptors, and abdominal trauma. We present a 29-year-old Nigerian
      woman with fungating lower abdominal wall tumor. This tumor is rare, a high index
      of suspicion will be very important in making the diagnosis.

PMID- 29643737
TI  - Ectopic Pancreas Causing Partial Gastric Outlet Obstruction: A Case Report and
      Review of Literature.
AB  - Ectopic pancreas is a rare cause of gastric outlet obstruction, perhaps rarer
      still among Africans. Although the entity is known, the diagnostic challenges are
      enormous, especially in the poor-resource environment. Gastric outlet obstruction
      resulting from ectopic pancreas in an adult is the first of its kind in our
      center; we, therefore, present this case to describe the challenges faced with
      diagnosis, treatment, and the lesson learned. Ectopic pancreas should be
      considered in the differential diagnosis of gastric outlet obstruction.

PMID- 29643738
TI  - An Alternative Technique in the Control of Massive Presacral Rectal Bleeding:
      Fixation of GORE-TEX(r) Aortic Patch.
AB  - The presacral venous system is located under the pelvic fascia covering the
      anterior of the sacrum and consists of two lateral sacral veins, middle sacral
      vein, and the veins that communicate them. The presacral venous system can be
      easily damaged and causes serious bleeding which is difficult to control and may
      cause intraoperative mortality. Its incidence varies between 3% and 9.4%.
      Although several methods have been tried to control presacral bleeding, the
      definitive method of treatment has not yet been identified. We present here our
      alternative technique in control of massive presacral massive bleeding developed
      from the presacral plexus secondary to the traction of the specimen during the
      dissection. The bleeding could not be controlled despite the use of all technical
      possibilities such as packing, ligation, and hemostatic agents. Bleeding control
      was provided by GORE-TEX(r) graft. We conclude that fixation of GORE-TEX(r)
      aortic patch should be kept in mind for uncontrolled massive presacral bleeding.

PMID- 29643739
TI  - Experiences, expectations and challenges of an interactive mobile phone-based
      system to support self-management of hypertension: patients' and professionals'
      perspectives.
AB  - Background: A well-controlled blood pressure (BP) reduces cardiovascular
      complications. Patient participation in care using technology may improve the
      current situation of only 13.8% of adults diagnosed with hypertension worldwide
      having their BP under control. Objective: The objective of this study was to
      explore patients' and professionals' experiences of and expectations for an
      interactive mobile phone-based system to support self-management of hypertension.
      Methods: The self-management system consists of: 1) a mobile phone platform for
      self-reports, motivational messages and reminders; 2) a device for measuring BP
      and 3) graphical feedback of self-reports. Patients diagnosed with high BP (n=20)
      and their treating professionals (n=7) participated in semi-structured
      interviews, after 8 weeks use of the system in clinical practice. Data were
      analyzed thematically. Results: The self-reporting of BP, symptoms, medication
      use, medication side effects, lifestyle and well-being was perceived to offer
      insight into how daily life activities influenced BP and helped motivate a
      healthy lifestyle. Taking increased responsibility as a patient, by understanding
      factors affecting one's well-being, was reported as an enabling factor for a more
      effective care. Based on the experiences, some challenges were mentioned: for
      adoption of the system into clinical practice, professionals' educational role
      should be extended and there should be a reorganization of care to fully benefit
      from technology. The patients and professionals gave examples of further
      improvements to the system, for example, related to the visualization of graphs
      from self-reports and an integration of the system into the general technical
      infrastructure. These challenges are important on the path to accomplishing
      adoption. Conclusion: The potential of a more autonomous, knowledgeable and
      active patient, through use of the interactive mobile system would improve
      outcomes of hypertension treatment, which has been desired for decades.
      Documentation and visualization of patients' self-reports and the possibilities
      to communicate these with professionals may be a significant resource for person
      centered care.

PMID- 29643741
TI  - An Improved Test of Equality of Mean Directions for the Langevin-von Mises-Fisher
      Distribution.
AB  - A multi-sample test for equality of mean directions is developed for populations
      having Langevin-von Mises-Fisher distributions with a common unknown
      concentration. The proposed test statistic is a monotone transformation of the
      likelihood ratio. The high-concentration asymptotic null distribution of the test
      statistic is derived. In contrast to previously suggested high-concentration
      tests, the high-concentration asymptotic approximation to the null distribution
      of the proposed test statistic is also valid for large sample sizes with any
      fixed nonzero concentration parameter. Simulations of size and power show that
      the proposed test outperforms competing tests. An example with three-dimensional
      data from an anthropological study illustrates the practical application of the
      testing procedure.

PMID- 29643740
TI  - Internal stress and defect-related free volume in submicrocrystalline Ni studied
      by neutron diffraction and difference dilatometry.
AB  - A combined study of neutron diffraction and difference dilatometry on
      submicrocrystalline Ni prepared by high pressure torsion aims at studying the
      anisotropic behaviour during dilatometry and its relation to internal stress and
      structural anisotropy. Macroscopic stresses were undetectable in the dilatometer
      samples. Along with specific tests such as post cold-rolling, this shows that an
      observed anisotropic length change upon annealing is not caused by internal
      stress, but can be explained by the inherent microstructure, i.e. the anisotropic
      annealing of relaxed vacancies at grain boundaries of shape-anisotropic
      crystallites.

PMID- 29643742
TI  - Effects of interprofessional education for medical and nursing students:
      enablers, barriers and expectations for optimizing future interprofessional
      collaboration - a qualitative study.
AB  - Background: To ensure high quality patient care an effective interprofessional
      collaboration between healthcare professionals is required. Interprofessional
      education (IPE) has a positive impact on team work in daily health care practice.
      Nevertheless, there are various challenges for sustainable implementation of IPE.
      To identify enablers and barriers of IPE for medical and nursing students as well
      as to specify impacts of IPE for both professions, the 'Cooperative academical
      regional evidence-based Nursing Study in Mecklenburg-Western Pomerania' (Care-N
      Study M-V) was conducted. The aim is to explore, how IPE has to be designed and
      implemented in medical and nursing training programs to optimize students' impact
      for IPC. Methods: A qualitative study was conducted using the Delphi method and
      included 25 experts. Experts were selected by following inclusion criteria: (a)
      ability to answer every research question, one question particularly competent,
      (b) interdisciplinarity, (c) sustainability and (d) status. They were purposely
      sampled. Recruitment was based on existing collaborations and a web based search.
      Results: The experts find more enablers than barriers for IPE between medical and
      nursing students. Four primary arguments for IPE were mentioned: (1) development
      and promotion of interprofessional thinking and acting, (2) acquirement of shared
      knowledge, (3) promotion of beneficial information and knowledge exchange, and
      (4) promotion of mutual understanding. Major barriers of IPE are the coordination
      and harmonization of the curricula of the two professions. With respect to the
      effects of IPE for IPC, experts mentioned possible improvements on (a) patient
      level and (b) professional level. Experts expect an improved patient-centered
      care based on better mutual understanding and coordinated cooperation in
      interprofessional health care teams. To sustainably implement IPE for medical and
      nursing students, IPE needs endorsement by both, medical and nursing faculties.
      Conclusion: In conclusion, IPE promotes interprofessional cooperation between the
      medical and the nursing profession. Skills in interprofessional communication and
      roles understanding will be primary preconditions to improve collaborative
      patient-centered care. The impact of IPE for patients and caregivers as well as
      for both professions now needs to be more specifically analysed in prospective
      intervention studies.

PMID- 29643743
TI  - Evidence-based approaches to reduce cancer health disparities: Discover, develop,
      deliver, and disseminate.
AB  - The Texas Center for Health Disparities (TCHD) at the University of North Texas
      Health Science Center is a National Institute on Minority Health and Health
      Disparities-funded, specialized center of excellence for health disparities. TCHD
      organized its 12th annual conference focusing on "Evidence-Based Approaches to
      Reduce Cancer Health Disparities: Discover, Develop, Deliver, and Disseminate."
      At this conference, experts in health care, biomedical sciences, and public
      health gathered to discuss the current status and strategies for reducing cancer
      health disparities. The meeting was conducted in three sessions on breast cancer,
      prostate cancer, and colorectal cancer disparities, in addition to roundtable
      discussions and a poster session. Each session highlighted differences in the
      effects of cancer, based on factors such as race/ethnicity, gender, socioeconomic
      status, and geographical location. In each session, expert speakers presented
      their findings, and this was followed by a discussion panel made up of experts in
      that field and cancer survivors, who responded to questions from the audience.
      This article summarizes the approaches to fundamental, translational, clinical,
      and public health issues in cancer health disparities discussed at the
      conference.

PMID- 29643744
TI  - Cost-effectiveness of the recommended medical intervention for the treatment of
      dysmenorrhea and endometriosis in Japan.
AB  - Background and objective: This study aims to assess the cost-effectiveness of
      early physician consultation and guideline-based intervention to prevent
      endometriosis and/or disease progression using oral contraceptive (OC) and
      progestin compared to follow-up of self-care for dysmenorrhea in Japan. Methods:
      A yearly-transmitted Markov model of five major health states with four sub
      medical states was constructed. Transition probabilities among health and medical
      states were derived from Japanese epidemiological patient surveys and converted
      to appropriate parameters for inputting into the model. The dysmenorrhea and
      endometriosis-associated direct costs included inpatient, outpatient visit,
      surgery, and medication (OC agents, over-the-counter drugs), etc. The utility
      measure for patients with phase I-IV endometriosis comprised a visual analogue
      scale. We estimated the cost per quality-adjusted life year (QALY) at a time
      horizon of 23 years. An annual discount rate at 3% for both cost and outcome was
      considered. Results: The base case outcomes indicated that the intervention would
      be more cost-effective than self-care, as the incremental cost-effectiveness
      ratio (ICER) yielded 115,000 JPY per QALY gained from the healthcare payers'
      perspective and the societal monetary value (SMV) was approximately positive
      3,130,000 JPY, favoring the intervention in the cost-benefit estimate. A tornado
      diagram depicting the stochastic sensitivity analysis of the ICER and SMV from
      both the healthcare payers' and societal perspectives confirmed the robustness of
      the base case. A probabilistic analysis resulting from 10,000-time Monte Carlo
      simulations demonstrated efficiency at willingness-to-pay thresholds in more than
      90% of the iterations. Conclusions: The present analysis demonstrated that early
      physician consultation and guideline-based intervention would be more cost
      effective than self-care in preventing endometriosis and/or disease progression
      for patients with dysmenorrhea in Japan.

PMID- 29643745
TI  - Prospective motion correction for 3D GRASE pCASL with volumetric navigators.
AB  - We propose a prospective motion correction approach for background suppressed
      (BS) segmented 3D GRASE pCASL using volumetric EPI-based navigators (vNavs),
      which causes minimal contrast change and no extra time. vNavs reduced motion
      artifacts effectively and increased temporal signal-to-noise ratio (t-SNR).
      Principle component analysis (PCA) is able to further reduce residual motion
      artifacts and restore the details of gyral structure in perfusion weighted
      images..

PMID- 29643746
TI  - Bias and SNR of T1 estimates derived from joint fitting of actual flip-angle and
      FLASH imaging data with variable flip angles.
AB  - Previous work has suggested fitting joint AFI/FLASH data for T1 and B1+ by
      minimizing the 2-norm of the difference between the signal model and measurements
      will produce unbiased estimates of T1. We demonstrate that, contrary to previous
      results, the estimator has a substantial bias that varies with both the true T1
      and B1+, and the receive channel count. We also demonstrate that the correct ML
      estimator removes the effect of channel count, and that the choice of AFI
      protocol has a larger impact of the quality of estimates than the addition of an
      extra FLASH scan.

PMID- 29643747
TI  - Accurate High-speed 3D-Registration of EPI vNavs for Head Motion Correction.
AB  - Low-resolution, whole-head volumes can be acquired rapidly with EPI-based
      volumetric navigators (vNavs). vNavs interspersed in a longer scan are widely
      used for prospective motion correction in a variety of sequences. To further
      improve the accuracy and flexibility of vNavs, we present a novel registration
      algorithm, tailored specifically for the vNavs application. Accuracy of the
      algorithm is tested on navigator volumes acquired with human volunteers at three
      isotropic resolutions, 6.4mm, 8mm, and 10mm, using a series of field of view
      (FOV) rotations and translations to provide ground truth rigid "motion".

PMID- 29643748
TI  - Randomness in nonlocal games between mistrustful players.
AB  - If two quantum players at a nonlocal game G achieve a superclassical score, then
      their measurement outcomes must be at least partially random from the perspective
      of any third player. This is the basis for device-independent quantum
      cryptography. In this paper we address a related question: does a superclassical
      score at G guarantee that one player has created randomness from the perspective
      of the other player? We show that for complete-support games, the answer is yes:
      even if the second player is given the first player's input at the conclusion of
      the game, he cannot perfectly recover her output. Thus some amount of local
      randomness (i.e., randomness possessed by only one player) is always obtained
      when randomness is certified from nonlocal games with quantum strategies. This is
      in contrast to non-signaling game strategies, which may produce global randomness
      without any local randomness. We discuss potential implications for cryptographic
      protocols between mistrustful parties.

PMID- 29643749
TI  - Deciding When Less Is More: The Crossroads of Withdrawing Antiepileptic Drugs.

PMID- 29643751
TI  - Malformations of Cortical Development: A Structural and Functional MRI
      Perspective.

PMID- 29643750
TI  - Epilepsy-Specific Citation Classics Revisited.

PMID- 29643752
TI  - Predicting a Storm by Watching the Waves.

PMID- 29643753
TI  - Reefer to the Rescue: The Dope on Cannabidiol as a Multi-Symptom Panacea for
      Dravet Syndrome.

PMID- 29643754
TI  - Deja Vu: Same Pattern of Neuron Activation From Seizure to Seizure, Only the
      Timing Changes.

PMID- 29643756
TI  - Population Viability Analysis of the Endangered Roan Antelope in Ruma National
      Park, Kenya, and Implications for Management.
AB  - Population viability analysis (PVA) was used to (1) establish causes of roan
      population decline for the past 30 years in Ruma National Park (RNP), the only
      park where wild roans remain in Kenya, and (2) predict the probability of roan
      persistence under existing and alternative management options. PVA was done using
      long-term data based on population dynamics, life history, climatic conditions,
      and expert knowledge. Poaching was identified as the main cause of roan decline
      in RNP. Several antipoaching and prioritized habitat management interventions to
      promote population recovery and sustainable conservation of roans are described.
      PVA predictions indicated that, without these interventions, the roan population
      cannot persist more than 3 decades. Furthermore, ensuring sustainable
      conservation of roans in RNP will boost tourism in Western Kenyan and thus
      alleviate poverty in this part of the country. Improved income from tourism will
      reduce the possible pressures from hunting and give greater incentives for local
      people to be actively engaged in roan conservation.

PMID- 29643755
TI  - Alpinia Essential Oils and Their Major Components against Rhodnius nasutus, a
      Vector of Chagas Disease.
AB  - Species of the genus Alpinia are widely used by the population and have many
      described biological activities, including activity against insects. In this
      paper, we describe the bioactivity of the essential oil of two species of Alpinia
      genus, A. zerumbet and A. vittata, against Rhodnius nasutus, a vector of Chagas
      disease. The essential oils of these two species were obtained by
      hydrodistillation and analyzed by GC-MS. The main constituent of A. zerumbet
      essential oil (OLALPZER) was terpinen-4-ol, which represented 19.7% of the total
      components identified. In the essential oil of A. vittata (OLALPVIT) the
      monoterpene beta-pinene (35.3%) was the main constituent. The essential oils and
      their main constituents were topically applied on R. nasutus fifth-instar nymphs.
      In the first 10 min of application, OLALPVIT and OLALPZER at 125 MUg/mL provoked
      73.3% and 83.3% of mortality, respectively. Terpinen-4-ol at 25 MUg/mL and beta
      pinene at 44 MUg/mL provoked 100% of mortality. The monitoring of resistant
      insects showed that both essential oils exhibited antifeedant activity. These
      results suggest the potential use of A. zerumbet and A. vittata essential oils
      and their major constituents to control R. nasutus population.

PMID- 29643757
TI  - Conservation Status of the Family Orchidaceae in Spain Based on European,
      National, and Regional Catalogues of Protected Species.
AB  - This report reviews the European, National, and Regional catalogues of protected
      species, focusing specifically on the Orchidaceae family to determine which
      species seem to be well-protected and where they are protected. Moreover, this
      examination highlights which species appear to be underprotected and therefore
      need to be included in some catalogues of protection or be catalogued under some
      category of protection. The national and regional catalogues that should be
      implemented are shown, as well as what species should be included within them.
      This report should be a helpful guideline for environmental policies about
      orchid's conservation in Spain, at least at the regional and national level.
      Around 76% of the Spanish orchid flora are listed with any figure of protection
      or included in any red list, either nationally (about 12-17%) or regionally
      (72%).

PMID- 29643758
TI  - Prevalence of supplement use in recreationally active Kazakhstan university
      students.
AB  - Background: Little is known about the supplements use and recreational sport
      practices in Kazakhstan university students. Therefore, the aim of this study was
      to ascertain supplements use prevalence and their predictors in this population.
      Methods: Cross-sectional survey of both undergraduate and graduate level students
      was completed in 2017 et al.-Farabi Kazakh National University, the largest
      higher institution in the country, from almost all Schools. A 45-item
      questionnaire was used to record physical activity, supplements use, lifestyle
      attributes (smoking, alcohol, sleep, etc.) and eating habits, and adjusted
      regression models were used to verify predictors of supplements use. Results: Of
      the entire sample of 889 students (70% females), 526 (59%) were practicing
      recreational physical activity (RPA), and walking, jogging and track and field
      was the most popular activity type (38%). N = 151 (29%) students reported the use
      of any supplement (31% in men and 27% in women), whereas the most popular
      supplement type were vitamins. Supplement use was most prevalent in swimmers
      (55%). Age (odds ratio (OR) 1.19 (95% confidence interval (CI) 1.04-1.37), use of
      fitness tracker (OR 6.26 (95% CI 3.90-10.03)) and low-fat diet (OR 1.95 (95% CI
      1.23-3.10)), but not income predicted supplements use in adjusted models.
      Conclusions: With more than half of students exercising regularly, only less than
      one-third use supplements with a very strong association with fitness tracker
      use.

PMID- 29643759
TI  - Changes in H-Reflex Recruitment After Trans-Spinal Direct Current Stimulation
      With Multiple Electrode Configurations.
AB  - Trans-spinal direct current stimulation (tsDCS) is an electro-modulatory tool
      with possible application in the rehabilitation of spinal cord injury. TsDCS
      generates a small electric field, aiming to induce lasting, functional
      neuromodulation in the targeted neuronal networks. Earlier studies have shown
      significant modulatory effects after application of lumbar tsDCS. However, for
      clinical application, a better understanding of application specific factors is
      required. Our goal was to investigate the effect of different electrode
      configurations using lumbar spinal tsDCS on spinal excitability. We applied tsDCS
      (2.5 mA, 15 min) in 10 healthy subjects with three different electrode
      configurations: (1) Anode and cathode placed over vertebra T11, and the posterior
      left shoulder respectively (LSC-S) (one polarity), and (2) Both electrodes placed
      in equal distance (ED) (7 cm) above and below vertebra T11, investigated for two
      polarities (ED-Anodal/Cathodal). The soleus H-Reflex is measured before, during
      and after tsDCS in either electrode configuration or a sham condition. To account
      for genetic predispositions in response to direct current stimulation, subject
      BDNF genotype was assessed. Stimulation in configuration ED-Cathodal induced an
      amplitude reduction of the H-reflex, 30 min after tsDCS with respect to baseline,
      whereas none of the other configurations led to significant post intervention
      effects. BDNF genotype did not correlate with post intervention effects.
      Furthermore, we failed to replicate effects shown by a previous study, which
      highlights the need for a better understanding of methodological and subject
      specific influences on tsDCS outcome. The H-reflex depression after tsDCS
      (Config. ED-Cathodal) provides new insights and may foster our understanding of
      the working mechanism of tsDCS.

PMID- 29643760
TI  - A Comparison of Low-Complexity Real-Time Feature Extraction for Neuromorphic
      Speech Recognition.
AB  - This paper presents a real-time, low-complexity neuromorphic speech recognition
      system using a spiking silicon cochlea, a feature extraction module and a
      population encoding method based Neural Engineering Framework (NEF)/Extreme
      Learning Machine (ELM) classifier IC. Several feature extraction methods with
      varying memory and computational complexity are presented along with their
      corresponding classification accuracies. On the N-TIDIGITS18 dataset, we show
      that a fixed bin size based feature extraction method that votes across both time
      and spike count features can achieve an accuracy of 95% in software similar to
      previously report methods that use fixed number of bins per sample while using
      ~3* less energy and ~25* less memory for feature extraction (~1.5* less overall).
      Hardware measurements for the same topology show a slightly reduced accuracy of
      94% that can be attributed to the extra correlations in hardware random weights.
      The hardware accuracy can be increased by further increasing the number of hidden
      nodes in ELM at the cost of memory and energy.

PMID- 29643761
TI  - Capacity, Fidelity, and Noise Tolerance of Associative Spatial-Temporal Memories
      Based on Memristive Neuromorphic Networks.
AB  - We have calculated key characteristics of associative (content-addressable)
      spatial-temporal memories based on neuromorphic networks with restricted
      connectivity-"CrossNets." Such networks may be naturally implemented in
      nanoelectronic hardware using hybrid memristive circuits, which may feature
      extremely high energy efficiency, approaching that of biological cortical
      circuits, at much higher operation speed. Our numerical simulations, in some
      cases confirmed by analytical calculations, show that the characteristics depend
      substantially on the method of information recording into the memory. Of the four
      methods we have explored, two methods look especially promising-one based on the
      quadratic programming, and the other one being a specific discrete version of the
      gradient descent. The latter method provides a slightly lower memory capacity (at
      the same fidelity) then the former one, but it allows local recording, which may
      be more readily implemented in nanoelectronic hardware. Most importantly, at the
      synchronous retrieval, both methods provide a capacity higher than that of the
      well-known Ternary Content-Addressable Memories with the same number of
      nonvolatile memory cells (e.g., memristors), though the input noise immunity of
      the CrossNet memories is lower.

PMID- 29643762
TI  - Persistent Adult Neuroimmune Activation and Loss of Hippocampal Neurogenesis
      Following Adolescent Ethanol Exposure: Blockade by Exercise and the Anti
      inflammatory Drug Indomethacin.
AB  - Alcohol abuse and binge drinking are common during adolescence, a developmental
      period characterized by heightened neuroplasticity. Animal studies reveal that
      adolescent ethanol exposure decreases hippocampal neurogenesis that persists into
      adulthood, but the mechanism remains to be fully elucidated. Using a rodent model
      of adolescent intermittent ethanol (AIE; 5.0 g/kg, i.g., 2-days on/2-days off
      from postnatal day [P]25 to P55), we tested the hypothesis that AIE-induced
      upregulation of neuroimmune signaling contributes to the loss of hippocampal
      neurogenesis in adulthood. We found that AIE caused upregulation of multiple
      proinflammatory Toll-like receptors (TLRs), increased expression of
      phosphorylated NF-kappaB p65 (pNF-kappaB p65) and the cell death marker cleaved
      caspase 3, and reduced markers of neurogenesis in the adult (P80) hippocampus,
      which is consistent with persistently increased neuroimmune signaling reducing
      neurogenesis. We observed a similar increase of pNF-kappaB p65-immunoreactive
      cells in the post-mortem human alcoholic hippocampus, an effect that was
      negatively correlated with age of drinking onset. Voluntary wheel running from
      P24 to P80 prevented the AIE-induced loss of neurogenesis markers (i.e., nestin
      and doublecortin) in the adult hippocampus that was paralleled by blockade of
      increased expression of the cell death marker cleaved caspase 3. Wheel running
      also prevented the AIE-induced increase of hippocampal pNF-kappaB p65 and
      induction of neuroimmune NF-kappaB target genes, including TNFalpha and
      IkappaBalpha in the adult brain. Administration of the anti-inflammatory drug
      indomethacin during AIE prevented the loss of neurogenesis markers (i.e., nestin
      and doublecortin) and the concomitant increase of cleaved caspase 3, an effect
      that was accompanied by blockade of the increase of pNF-kappaB p65. Similarly,
      administration of the proinflammatory TLR4 activator lipopolysaccharide resulted
      in a loss of doublecortin that was paralleled by increased expression of cleaved
      caspase 3 and pNF-kappaB p65 in the hippocampal dentate gyrus of CON animals that
      mimicked the AIE-induced loss of neurogenesis. Taken together, these data suggest
      that exercise and anti-inflammatory drugs protect against adolescent binge
      ethanol-induced brain neuroimmune signaling and the loss of neurogenesis in the
      adult hippocampus.

PMID- 29643763
TI  - No Gender Differences in Egocentric and Allocentric Environmental Transformation
      After Compensating for Male Advantage by Manipulating Familiarity.
AB  - The present study has two-fold aims: to investigate whether gender differences
      persist even when more time is given to acquire spatial information; to assess
      the gender effect when the retrieval phase requires recalling the pathway from
      the same or a different reference perspective (egocentric or allocentric).
      Specifically, we analyse the performance of men and women while learning a path
      from a map or by observing an experimenter in a real environment. We then asked
      them to reproduce the learned path using the same reference system (map learning
      vs. map retrieval or real environment learning vs. real environment retrieval) or
      using a different reference system (map learning vs. real environment retrieval
      or vice versa). The results showed that gender differences were not present in
      the retrieval phase when women have the necessary time to acquire spatial
      information. Moreover, using the egocentric coordinates (both in the learning and
      retrieval phase) proved easier than the other conditions, whereas learning
      through allocentric coordinates and then retrieving the environmental information
      using egocentric coordinates proved to be the most difficult. Results showed that
      by manipulating familiarity, gender differences disappear, or are attenuated in
      all conditions.

PMID- 29643764
TI  - The IDH1 Mutation-Induced Oncometabolite, 2-Hydroxyglutarate, May Affect DNA
      Methylation and Expression of PD-L1 in Gliomas.
AB  - Background: Malignant gliomas are heterogeneous brain tumors with the potential
      for aggressive disease progression, as influenced by suppressive immunoediting.
      Given the success and enhanced potential of immune-checkpoint inhibitors in
      immunotherapy, we focused on the connections between genetic alterations affected
      by IDH1 mutations and immunological landscape changes and PDL-1 expression in
      gliomas. Methods: Paired surgically resected tumors from lower-grade gliomas
      (LGGs) and glioblastomas (GBM) were investigated, and a genetic analysis of
      patients' primary tumor samples culled from TCGA datasets was performed. Results:
      The results demonstrate that when compared with IDH1-mutant tumors, IDH1 wildtype
      tumors represent an immunosuppression landscape and elevated levels of PD-L1
      expression. DNA hypo-methylation of the PD-L1 gene, as well as high gene and
      protein expressions, were observed in the wildtype tumors. We also found that
      quantitative levels of IDH1 mutant proteins were positively associated with
      recurrence-free survival (RFS). A key product of the IDH1 mutation (2
      hydroxyglutarate) was found to transiently increase DNA methylation and suppress
      PD-L1 expression. Conclusions: IDH1 mutations impact the immune landscape of
      gliomas by affecting immune infiltrations and manipulating checkpoint ligand PD
      L1 expression. Applications of immune checkpoint inhibitors may be beneficial for
      chemoradiation-insensitive IDH1-wildtype gliomas.

PMID- 29643765
TI  - miRNA Long-Term Response to Early Metabolic Environmental Challenge in
      Hypothalamic Arcuate Nucleus.
AB  - Epidemiological reports and studies using rodent models indicate that early
      exposure to nutrient and/or hormonal challenges can reprogram metabolism at
      adulthood. Hypothalamic arcuate nucleus (ARC) integrates peripheral and central
      signals to adequately regulate energy homeostasis. microRNAs (miRNAs) participate
      in the control of gene expression of large regulatory networks including many
      signaling pathways involved in epigenetics regulations. Here, we have
      characterized and compared the miRNA population of ARC of adult male rats
      continuously exposed to a balanced metabolic environment to the one of adult male
      rats exposed to an unbalanced high-fat/high-carbohydrate/moderate-protein
      metabolic environment during the perinatal period and/or at adulthood that
      consequently displayed hyperinsulinemia and/or hyperleptinemia. We identified
      more than 400 miRNA species in ARC of adult male rats. By comparing the miRNA
      content of six biological replicates in each of the four perinatal/adult
      environments/rat groups, we identified the 10 miRNAs specified by clusters miR
      96/182/183, miR-141/200c, and miR-200a/200b/429 as miRNAs of systematic and
      uncommonly high variation of expression. This uncommon variation of expression
      may underlie high individual differences in aging disease susceptibilities. By
      comparing the miRNA content of the adult ARC between the rat groups, we showed
      that the miRNA population was not affected by the unbalanced adult environment
      while, in contrast, the expression of 11 miRNAs was repeatedly impacted by the
      perinatal unbalanced environment. Our data revealed a miRNA response of adult ARC
      to early metabolic environmental challenge.

PMID- 29643766
TI  - Spatiotemporal Control of GPR37 Signaling and Its Behavioral Effects by
      Optogenetics.
AB  - Despite the progress in deorphanization of G Protein-Coupled Receptors (GPCRs),
      ~100 GPCRs are still classified as orphan receptors without identified endogenous
      ligands and with unknown physiological functions. The lack of endogenous ligands
      triggering GPCR signaling has hampered the study of orphan GPCR functions. Using
      GPR37 as an example, we provide here the first demonstration of the
      channelrhodopsin 2 (ChR2)-GPCR approach to bypass the endogenous ligand and
      selectively activate the orphan GPCR signal by optogenetics. Inspired by the opto
      XR approach, we designed the ChR2-GPR37 chimera, in which the corresponding parts
      of GPR37 replaced the intracellular portions of ChR2. We showed that optogenetic
      activation of ChR2/opto-GPR37 elicited specific GPR37 signaling, as evidenced by
      reduced cAMP level, enhanced ERK phosphorylation and increased motor activity,
      confirming the specificity of opto-GPR37 signaling. Besides, optogenetic
      activation of opto-GPR37 uncovered novel aspects of GPR37 signaling (such as IP-3
      signaling) and anxiety-related behavior. Optogenetic activation of opto-GPR37
      permits the causal analysis of GPR37 activity in the defined cells and behavioral
      responses of freely moving animals. Importantly, given the evolutionarily
      conserved seven-helix transmembrane structures of ChR2 and orphan GPCRs, we
      propose that opto-GPR37 approach can be readily applied to other orphan GPCRs for
      their deorphanization in freely moving animals.

PMID- 29643768
TI  - miRNA-431 Prevents Amyloid-beta-Induced Synapse Loss in Neuronal Cell Culture
      Model of Alzheimer's Disease by Silencing Kremen1.
AB  - Synapse loss is well regarded as the underlying cause for the progressive decline
      of memory function over the course of Alzheimer's disease (AD) development.
      Recent observations suggest that the accumulation of the Wnt antagonist Dickkopf
      1 (Dkk1) in the AD brain plays a critical role in triggering synaptic
      degeneration. Mechanistically, Dkk1 cooperates with Kremen1 (Krm1), its
      transmembrane receptor, to block the Wnt/beta-catenin signaling pathway. Here, we
      show that silencing Krm1 with miR-431 prevents amyloid-beta-mediated synapse loss
      in cortico-hippocampal cultures isolated from triple transgenic 3xTg-AD mice.
      Exposure to AbetaDDL (an amyloid-beta derived diffusive ligand) or Dkk1 reduced
      the number of pre- and post-synaptic puncta in primary neuronal cultures, while
      treatment with miR-431 prevented synapse loss. In addition, treatment with miR
      431 also prevented neurite degeneration. Our findings demonstrate that miR-431
      protects synapses and neurites from Abeta-toxicity in an AD cell culture model
      and may be a promising therapeutic target.

PMID- 29643767
TI  - Utility of the Hebb-Williams Maze Paradigm for Translational Research in Fragile
      X Syndrome: A Direct Comparison of Mice and Humans.
AB  - To generate meaningful information, translational research must employ paradigms
      that allow extrapolation from animal models to humans. However, few studies have
      evaluated translational paradigms on the basis of defined validation criteria. We
      outline three criteria for validating translational paradigms. We then evaluate
      the Hebb-Williams maze paradigm (Hebb and Williams, 1946; Rabinovitch and
      Rosvold, 1951) on the basis of these criteria using Fragile X syndrome (FXS) as
      model disease. We focused on this paradigm because it allows direct comparison of
      humans and animals on tasks that are behaviorally equivalent (criterion #1) and
      because it measures spatial information processing, a cognitive domain for which
      FXS individuals and mice show impairments as compared to controls (criterion #2).
      We directly compared the performance of affected humans and mice across different
      experimental conditions and measures of behavior to identify which conditions
      produce comparable patterns of results in both species. Species differences were
      negligible for Mazes 2, 4, and 5 irrespective of the presence of visual cues,
      suggesting that these mazes could be used to measure spatial learning in both
      species. With regards to performance on the first trial, which reflects visuo
      spatial problem solving, Mazes 5 and 9 without visual cues produced the most
      consistent results. We conclude that the Hebb-Williams mazes paradigm has the
      potential to be utilized in translational research to measure comparable
      cognitive functions in FXS humans and animals (criterion #3).

PMID- 29643769
TI  - The Role of Physical Exercise to Improve the Browning of White Adipose Tissue via
      POMC Neurons.
AB  - Obesity is a public health issue that affects more than 600 million adults
      worldwide. The disease is characterized by fat accumulation, mainly in the
      abdominal area. The human body is mainly composed of two types of adipose tissue:
      white adipose tissue (WAT) and brown adipose tissue (BAT); however, the browning
      process generates a different type of brown fat-like adipocyte in WAT, which
      similar to BAT has thermogenic capacity by activating UCP-1. The hypothalamic
      arcuate nucleus plays an important role in WAT browning via POMC neurons, which
      are influenced by synergistic insulin and leptin signaling. On the other hand,
      stimulation of AgRP neurons suppresses WAT browning. The hypothalamic
      inflammatory process that occurs in obesity impairs insulin and leptin signaling
      in this tissue and, consequently, can decrease WAT browning. In addition,
      practicing physical exercise may be a great strategy for triggering the browning
      process since it reduces hypothalamic inflammation and increases POMC neurons
      gene expression. Moreover, physical exercise stimulates irisin gene expression,
      which has an important impact on thermogenesis, which in turn culminates in
      increased gene expression of proteins such as UCP-1 and Cidea, which are related
      to WAT browning. Furthermore, thermogenetic activation of WAT leads to increased
      energy expenditure, favoring obesity treatment. Therefore, this mini-review aimed
      to highlight the most recent studies that link the control of hypothalamic
      activity with the browning metabolism of adipose tissue in response to physical
      exercise.

PMID- 29643770
TI  - Neural Control of Startle-Induced Locomotion by the Mushroom Bodies and
      Associated Neurons in Drosophila.
AB  - Startle-induced locomotion is commonly used in Drosophila research to monitor
      locomotor reactivity and its progressive decline with age or under various
      neuropathological conditions. A widely used paradigm is startle-induced negative
      geotaxis (SING), in which flies entrapped in a narrow column react to a gentle
      mechanical shock by climbing rapidly upwards. Here we combined in vivo
      manipulation of neuronal activity and splitGFP reconstitution across cells to
      search for brain neurons and putative circuits that regulate this behavior. We
      show that the activity of specific clusters of dopaminergic neurons (DANs)
      afferent to the mushroom bodies (MBs) modulates SING, and that DAN-mediated SING
      regulation requires expression of the DA receptor Dop1R1/Dumb, but not
      Dop1R2/Damb, in intrinsic MB Kenyon cells (KCs). We confirmed our previous
      observation that activating the MB alpha'beta', but not alphabeta, KCs decreased
      the SING response, and we identified further MB neurons implicated in SING
      control, including KCs of the gamma lobe and two subtypes of MB output neurons
      (MBONs). We also observed that co-activating the alphabeta KCs antagonizes
      alpha'beta' and gamma KC-mediated SING modulation, suggesting the existence of
      subtle regulation mechanisms between the different MB lobes in locomotion
      control. Overall, this study contributes to an emerging picture of the brain
      circuits modulating locomotor reactivity in Drosophila that appear both to
      overlap and differ from those underlying associative learning and memory,
      sleep/wake state and stress-induced hyperactivity.

PMID- 29643771
TI  - Effective Subnetwork Topology for Synchronizing Interconnected Networks of
      Coupled Phase Oscillators.
AB  - A system consisting of interconnected networks, or a network of networks (NoN),
      appears diversely in many real-world systems, including the brain. In this study,
      we consider NoNs consisting of heterogeneous phase oscillators and investigate
      how the topology of subnetworks affects the global synchrony of the network. The
      degree of synchrony and the effect of subnetwork topology are evaluated based on
      the Kuramoto order parameter and the minimum coupling strength necessary for the
      order parameter to exceed a threshold value, respectively. In contrast to an
      isolated network in which random connectivity is favorable for achieving
      synchrony, NoNs synchronize with weaker interconnections when the degree
      distribution of subnetworks is heterogeneous, suggesting the major role of the
      high-degree nodes. We also investigate a case in which subnetworks with different
      average natural frequencies are coupled to show that direct coupling of
      subnetworks with the largest variation is effective for synchronizing the whole
      system. In real-world NoNs like the brain, the balance of synchrony and
      asynchrony is critical for its function at various spatial resolutions. Our work
      provides novel insights into the topological basis of coordinated dynamics in
      such networks.

PMID- 29643772
TI  - Periodic Visual Stimulation Induces Resting-State Brain Network Reconfiguration.
AB  - Periodic visual stimulation can evoke the steady-state visual potential (SSVEP)
      in the brain. Owing to its superior characteristics, the SSVEP has been widely
      used in neural engineering and cognitive neuroscience studies. However, the
      underlying mechanisms of the SSVEP are not well understood. In this study, we
      introduced a brain reconfiguration methodology to explore the possible mechanisms
      of the SSVEP. The EEG data from five periodic stimuli consistently indicated that
      the periodic visual stimulation could induce resting-state brain network
      reconfiguration and that the responses evoked by the stimuli were correlated to
      the network reconfiguration indexes. For each stimulus frequency, larger response
      amplitudes corresponded to higher reconfiguration indexes from the resting-state
      network to a stimulus-evoked network. These findings demonstrate that an external
      periodic visual stimulation can induce the modification of intrinsic oscillatory
      activities by reconfiguring resting-state activity at a network level, which
      could facilitate the responses evoked by the stimulus. These findings provide new
      insights into the response mechanisms of periodic visual stimulation.

PMID- 29643773
TI  - Using a Simple Neural Network to Delineate Some Principles of Distributed
      Economic Choice.
AB  - The brain uses a mixture of distributed and modular organization to perform
      computations and generate appropriate actions. While the principles under which
      the brain might perform computations using modular systems have been more
      amenable to modeling, the principles by which the brain might make choices using
      distributed principles have not been explored. Our goal in this perspective is to
      delineate some of those distributed principles using a neural network method and
      use its results as a lens through which to reconsider some previously published
      neurophysiological data. To allow for direct comparison with our own data, we
      trained the neural network to perform binary risky choices. We find that value
      correlates are ubiquitous and are always accompanied by non-value information,
      including spatial information (i.e., no pure value signals). Evaluation,
      comparison, and selection were not distinct processes; indeed, value signals even
      in the earliest stages contributed directly, albeit weakly, to action selection.
      There was no place, other than at the level of action selection, at which
      dimensions were fully integrated. No units were specialized for specific offers;
      rather, all units encoded the values of both offers in an anti-correlated format,
      thus contributing to comparison. Individual network layers corresponded to stages
      in a continuous rotation from input to output space rather than to functionally
      distinct modules. While our network is likely to not be a direct reflection of
      brain processes, we propose that these principles should serve as hypotheses to
      be tested and evaluated for future studies.

PMID- 29643774
TI  - Corrigendum: The Reality of Myoelectric Prostheses: Understanding What Makes
      These Devices Difficult for Some Users to Control.
AB  - [This corrects the article on p. 7 in vol. 10, PMID: 27597823.].

PMID- 29643775
TI  - Case Report of a Family Affected by Stickler Syndrome in Which Rhegmatogenous
      Retinal Detachment Occurred in Five Eyes of Three Siblings.
AB  - Purpose: Stickler syndrome is an autosomal dominant inherited disorder that is
      well known to be highly associated with the development of rhegmatogenous retinal
      detachment. In this study, we report the case of a family affected by Stickler
      syndrome in which rhegmatogenous retinal detachment developed in 5 eyes of 3
      siblings. Case Series: For treatment, we performed vitreous surgery on 1 eye of
      the eldest son, and bilateral scleral buckling surgery on the 2 younger children.
      A good postoperative outcome was obtained on the 4 eyes that underwent scleral
      buckling surgery, yet the prognosis was poor on the 1 eye that underwent
      vitrectomy due to redetachment of the retina and corneal complication. Since
      vitreous surgery was quite difficult due to strong vitreoretinal adhesion, we
      created an artificial posterior vitreous detachment via the bimanual technique
      combined with encircling. For the scleral buckling surgery, broad scleral
      extrusion was needed to seal multiple retinal breaks. Conclusions: The findings
      of this study showed a high prevalence of rhegmatogenous retinal detachment in a
      single family with Stickler syndrome. In these cases, scleral buckling surgery
      was effective for treating the detached retina, and some prophylactic treatment,
      such as laser photocoagulation to prevent the occurrence of rhegmatogenous
      retinal detachment, should be considered for such cases in the future.

PMID- 29643776
TI  - Patch Grafting Using an Ologen Collagen Matrix to Manage Tubal Exposure in
      Glaucoma Tube Shunt Surgery.
AB  - Purpose: To report the results using an ologen Collagen Matrix as a patch graft
      in eyes with tubal exposure after tube shunt surgery. Case Reports: Case 1 was an
      82-year-old man with tubal exposure in his right eye 26 months after receiving a
      Baerveldt glaucoma implant. The tube was covered by surrounding conjunctival
      tissue combined with subconjunctival placement of an ologen Collagen Matrix as a
      patch graft. Two years after implantation, the tube was not exposed. Anterior
      segment optical coherence tomography (AS-OCT) showed dense conjunctival tissue
      over the tube. Case 2 was an 82-year-old man with peripheral keratitis, anterior
      scleritis, and secondary glaucoma in the right eye who underwent tube shunt
      surgery using an Ahmed glaucoma valve and cataract surgery. Intraoperatively,
      scleritis-related scleral thinning prevented the tube from being covered fully by
      an autologous scleral flap. An ologen Collagen Matrix was placed over the scleral
      flap as a patch graft. Seventeen months after implantation, the tube was not
      exposed. Case 3 was a 52-year-old man with diabetic maculopathy and steroid
      induced glaucoma in the right eye who underwent tube shunt surgery using an Ahmed
      glaucoma valve. Intraoperatively, a flap defect prevented the tube from being
      covered fully by an autologous scleral flap. An ologen Collagen Matrix was placed
      over the scleral flap as a patch graft. Three weeks postoperatively, AS-OCT
      showed thick subconjunctival tissue over the tube. Three months after
      implantation, the tube was not exposed. Conclusions: The ologen Collagen Matrix
      can be used successfully as a patch graft to prevent and treat tubal exposure
      after tube shunt surgery.

PMID- 29643777
TI  - A Case of Retinal Detachment with Unique Optical Coherence Tomography Findings
      after Gamma Knife(r) Radiosurgery Treatment for Choroidal Melanoma.
AB  - Purpose: To report a case of retinal detachment with unique optical coherence
      tomography (OCT) findings after Gamma Knife(r) (GK; Elekta Instrument AB,
      Stockholm, Sweden) treatment for choroidal melanoma (CM). Case Report: A 48-year
      old woman underwent GK therapy for CM in her right eye from the macula to the
      temporal side. While the tumor subsequently shrank, the patient developed
      radiation retinopathy, which was treated with laser photocoagulation. The tumor
      lesions later subsided; however, her visual acuity (VA) decreased 8 years after
      the initial treatment. Although the tumor lesions in the right eye had become
      scarred, a bullous retinal detachment with fixed folds occurred in the superior
      nasal quadrants. OCT examination revealed a preretinal membrane, vitreoretinal
      traction, and an inner retinal break; however, no outer retinal break was clearly
      detectable. MRI scans showed no increase in tumorous lesions, and 123I-IMP SPECT
      imaging showed no photon accumulation. Thus, it was determined that there was no
      tumor activity. The corrected VA in her right eye was light perception, and it
      was determined that there was no indication for vitreous surgery. Conclusion: In
      this case, an inner retinal break was formed by the vitreoretinal traction around
      the scarred tumor and radiation retinopathy, thus suggesting the possibility of
      the development of a rhegmatogenous retinal detachment presumably complicated
      with an outer retinal break.

PMID- 29643778
TI  - Phthirus pubis Infestation of the Eyelids Presenting as Chronic
      Blepharoconjunctivitis in a 6-Year-Old Girl: A Case Report.
AB  - Purpose: To report the case of Phthirus pubis infestation of the eyelashes
      presenting as chronic blepharoconjunctivitis. Case Report: A 6-year-old girl
      presented with a 2-month history of blepharoconjunctivitis unresponsive to
      topical antibiotics in the left eye. Slit-lamp examination revealed the presence
      of nits and adult parasites on the eyelashes. Parasitological examination
      confirmed adult forms and nits of Phthirus pubis. There was no evidence of
      infestation elsewhere. Outcome was favourable with mechanical removal and
      application of petroleum jelly. Conclusion: Careful slit-lamp examination of the
      eyelashes should be done in all patients presenting with ocular irritation
      symptoms.

PMID- 29643779
TI  - The Safety and Effectiveness of a Novel Annular Keratopigmentation Method: A Case
      Report.
AB  - Background: We investigated the safety and effectiveness of a novel aesthetic
      femtosecond-assisted annular keratopigmentation technique. Case Report: A 21-year
      old female patient in good general and ophthalmological health with the wish to
      change the colour of her eyes was treated with a femtosecond-assisted annular
      keratopigmentation technique. Pigment was inserted in a channel in the cornea
      (external diameter 9.3 mm; internal diameter 5.5 mm) created with a femtosecond
      laser at a depth of 225 MUm. Eight months post-operatively, there were no signs
      of leakage, diffusion, inflammation or any other detrimental effects on the
      cornea both objectively and subjectively. Conclusion: This procedure is a
      promising safe and effective option for those who want annular keratopigmentation
      for aesthetic reasons.

PMID- 29643780
TI  - Intravenous Drug Use-Associated Scopulariopsis Endophthalmitis Treated with
      Systemic and Intravitreal Voriconazole.
AB  - Purpose: To report a case of intravenous (i.v.) heroin use-associated endogenous
      endophthalmitis caused by Scopulariopsis fungal species, and its response to
      intravitreal and oral voriconazole treatments. Patient: A 21-year-old-female with
      chronic hepatitis C and i.v. heroin use presented with subacute decreased vision
      to hand motion in her left eye. Results: Endogenous fungal endophthalmitis caused
      by Scopulariopsis was confirmed by vitreous biopsy. The patient improved
      clinically after vitrectomy with intravitreal voriconazole and 3 weeks of oral
      voriconazole. The final vision was 20/60 after 6 months. Conclusions:
      Scopulariopsis is a rare cause of endophthalmitis, and is often difficult to
      treat due to its resistance to commonly used antifungals. This case is the first
      report of Scopulariopsis endophthalmitis secondary to i.v. drug use.

PMID- 29643781
TI  - Two Cases of Rhegmatogenous Retinal Detachment Associated with Asteroid Hyalosis.
AB  - Background: To report two cases of rhegmatogenous retinal detachment (RRD)
      associated with asteroid hyalosis (AH). Case Presentation: Two patients presented
      with RRD originating from a flap tear. Case 1 involved a 62-year-old male who was
      found to have bullous RRD in his left eye originating from a flap tear. During
      vitreous surgery, a thick vitreous cortex was found to have strongly adhered to
      the entire retinal surface, from the center to the periphery. A bimanual method
      was then used in conjunction with the vitrectomy to create an artificial
      posterior vitreous detachment. After surgery, the retina was successfully
      reattached, and his corrected visual acuity (VA) improved. Case 2 involved a 70
      year-old male who was found to have localized RRD in his left eye originating
      from a flap tear. During vitreous surgery, a thick vitreous cortex was found to
      have strongly adhered to the entire retinal surface. After surgery, the retina
      was successfully reattached, and his corrected VA improved. Conclusions: RRD
      associated with AH presents with stronger vitreoretinal adhesion compared to
      typical RRD, thus requiring a more complicated surgical technique to properly
      treat the patient.

PMID- 29643782
TI  - Repair of Traumatic Rhegmatogenous Retinal Detachment Combined with Congenital
      Falciform Retinal Detachment.
AB  - Purpose: To report a case of surgical repair of traumatic rhegmatogenous retinal
      detachment combined with congenital falciform retinal detachment (FRD). Methods:
      A retrospective case report. Results: A 36-year-old man with traumatic
      rhegmatogenous retinal detachment complicating a previously known FRD was
      successfully treated despite residual FRD following pars plana lensectomy,
      vitrectomy, and encircling scleral buckling. His best corrected visual acuity
      improved from hand motion at 50 cm to 20/1,000. Conclusion: We concluded that the
      root of the FRD is susceptible to trauma because of the contraction of
      fibrovascular tissue. The early intervention of modern vitrectomy to traumatic
      rhegmatogenous retinal detachment complicating a previously known FRD is an
      important consideration for enhanced quality of care and optimal patient
      outcomes.

PMID- 29643783
TI  - Tamoxifen Use in a Patient with Idiopathic Macular Telangiectasia Type 2.
AB  - Crystalline deposits and neurosensory retinal cavitary changes can develop in
      both tamoxifen retinopathy and nonproliferative idiopathic macular telangiectasia
      type 2 (MacTel2). MacTel2 is typically differentiated from tamoxifen retinopathy
      based on the presence of late leakage and mid-phase telangiectatic vessels on
      fluorescein angiography (FA) and the presence of hyperautofluorescence. Unlike
      MacTel2, tamoxifen retinopathy is known to be a progressive disease and the
      cessation of tamoxifen results in resolution of retinopathy. We report a unique
      case of nonproliferative MacTel2 in a 36-year-old Hispanic woman with tamoxifen
      use and the vision outcome 30 months after cessation of tamoxifen. The FA and
      optical coherence tomography angiography findings of this patient support the
      diagnosis of MacTel2, but her cessation of tamoxifen led to partial reversal of
      the topographic findings and improvement in visual acuity. This patient is also
      unique in the unusually young age of presentation for MacTel2. Our case supports
      that there are common pathways in the pathogenesis of tamoxifen retinopathy and
      MacTel2, and tamoxifen use could potentially accelerate foveal atrophy in
      patients with MacTel2.

PMID- 29643784
TI  - Clinical Efficacy and Safety of the EX-PRESS Filtration Device in Patients with
      Advanced Neovascular Glaucoma and Proliferative Diabetic Retinopathy.
AB  - Background: The prognosis of conventional filtration surgery in eyes with
      neovascular glaucoma (NVG) is limited due to increased fibrovascular
      proliferation or bleeding. This study aims to evaluate the safety and efficacy of
      the EX-PRESS filtration device in the management of NVG associated with
      proliferative diabetic retinopathy (PDR). Methods: In this retrospective case
      series, we reviewed the medical records of patients diagnosed as having NVG
      associated with PDR who underwent EX-PRESS filtration surgery. The main outcome
      measures were: postoperative intraocular pressure (IOP), the percent of IOP drop,
      the number of glaucoma medications, visual acuity, and complications of surgery.
      Successful surgery was defined as an IOP <22 mm Hg and >5 mm Hg with or without
      additional glaucoma surgery, and no loss of light perception or less than a 2
      line decrease on the Snellen chart of the best corrected visual acuity (BCVA).
      Results: Five patients (5 eyes) were included in this study. The mean
      preoperative IOP was 33.4 +/- 5.9 mm Hg compared to an IOP of 17.0 +/- 3.0 mm Hg
      at the last follow-up (p = 0.003). The mean number of preoperative anti-glaucoma
      medications was 3.8 +/- 0.4 compared to 2.2 +/- 1.5 (p = 0.06) at the last follow
      up visit. Final visual acuity improved or stabilized within 1 Snellen line in all
      5 patients. Three patients had a "hypertensive phase" (defined as an IOP >21 mm
      Hg during the first 6 postoperative months) which resolved within 2 months. Two
      patients developed a hyphema that resolved spontaneously. None of the patients
      experienced any serious complications. Conclusion: EX-PRESS filtration device has
      a good IOP-lowering effect and a low rate of complications in patients with
      advanced NVG associated with PDR. In addition, there was no loss of light
      perception or no line decrease of the BCVA.

PMID- 29643785
TI  - Periorbital Necrobiotic Xanthogranuloma Successfully Treated with Intravenous
      Immunoglobulin.
AB  - Background: Necrobiotic xanthogranuloma (NXG) is a rare non-Langerhans
      histiocytosis with cutaneous manifestations, most commonly of the periorbital
      skin, and is often associated with hematologic disorders such as monoclonal
      gammopathy. Treatment of NXG is notoriously difficult, and fraught with
      recurrence and progression. Case Presentation: The authors describe a case of NXG
      with periorbital involvement in a patient with a complex autoimmune and
      hematologic medical history. The biopsy of this rare lesion prompted subsequent
      evaluation for an underlying disorder, which led to the diagnosis of multiple
      myeloma. Her NXG lesions demonstrated remarkable clinical improvement after
      treatment with intravenous immunoglobulin (IVIG). Conclusions: This case
      demonstrates the ophthalmologist's critical role in the diagnosis and management
      of NXG, as early detection cannot only prevent ophthalmic consequences such as
      ocular perforation and blindness, but also prompt further investigation that may
      reveal an underlying disorder or systemic involvement, including hematologic
      malignancy as in this case. NXG has been effectively treated with IVIG in a
      handful of reported cases. To the author's knowledge, this is the third case of
      periorbital NXG successfully treated with IVIG, and the first in the ophthalmic
      literature.

PMID- 29643786
TI  - Association of Optic Nerve Head Drusen with Best Vitelliform Macular Dystrophy: A
      Case Series.
AB  - Purpose: To report the association of optic nerve head (ONH) drusen with Best
      vitelliform macular dystrophy (BVMD). Methods: Chart review. Patients: Five
      patients from 3 families. Results: Multimodal imaging and ophthalmic examination
      demonstrated findings consistent with ONH drusen, in association with BVMD, in 5
      patients. Conclusion: We report the association of BVMD with ONH drusen in 5
      patients. This combination has previously been reported only once. We recommend
      that patients with a diagnosis of BVMD undergo autofluorescence and ultrasound
      imaging of the optic nerve to help facilitate this diagnosis, as some ONH drusen
      can be buried.

PMID- 29643787
TI  - Optical Coherence Tomography Angiography of Foveal Neovascularization in Diabetic
      Retinopathy.
AB  - Purpose: To report a case of foveal neovascularization in a patient with
      proliferative diabetic retinopathy as seen on optical coherence tomography
      angiography (OCT-A). Methods: Multimodal imaging was used for diagnostic
      investigation. Patient: A 61-year-old male with a 16-year history of insulin
      dependent diabetes mellitus was referred to our medical retina department for
      examination and management. Meticulous fundus examination and multimodal imaging
      revealed proliferative diabetic retinopathy lesions, including neovascularization
      located in the foveal area. Results: OCT-A allowed us to detect the neovascular
      lesion, confirm that it originated from perifoveal capillaries, estimate its
      retinal depth, and evaluate the vessel blood flow in multiple layers. Conclusion:
      To the best of our knowledge this is the first report of OCT-A imaging of foveal
      neovascularization in diabetic retinopathy. OCT-A is a very useful examination
      for the diagnostic investigation of patients with diabetic retinopathy.

PMID- 29643788
TI  - Polypoidal Choroidal Vasculopathy Associated with Optic Disc Coloboma.
AB  - Purpose: To report a case of polypoidal choroidal vasculopathy associated with
      optic disc coloboma. Methods: Case report. Results: A 50-year-old woman presented
      with optic disc coloboma and retinochoroidal coloboma associated with subretinal
      hemorrhage and serous retinal detachment (SRD) in her left eye. Optical coherence
      tomography (OCT) confirmed SRD at the macula and showed a sharply elevated
      retinal epithelial detachment at the choroidal excavation. OCT also revealed
      choroidal cavitation along the temporal side of the optic coloboma. Fluorescein
      angiography showed hyperfluorescent dye leakage and indocyanine green angiography
      revealed polypoidal lesions. We diagnosed polypoidal choroidal vasculopathy
      (PCV). PCV was located at the end of the choroidal cavitation. Her left eye was
      treated with an intraocular injection of the anti-vascular endothelial growth
      factor aflibercept (2 mg). Photodynamic therapy was performed using the standard
      protocol 1 week after the intravitreal application of aflibercept. One month
      after the combined treatment, OCT showed completely resolved SRD and her symptoms
      disappeared. Her best-corrected visual acuity remained stable and no recurrence
      was found during a 12-month follow-up period. Conclusion: PCV associated with
      optic disc coloboma has not been previously reported. The morphological
      abnormality of choroidal cavitation and choroidal excavation connecting with
      optic disc coloboma may contribute to the development of PCV in this case.

PMID- 29643789
TI  - Alternating Hypotropia with Pseudoptosis: A New Phenotype of Congenital Cranial
      Dysinnervation Disorder.
AB  - Congenital cranial dysinnervation disorders, also known as CCDDs, are
      characterized by aberrant innervation to extraocular and facial muscles resulting
      in unusual forms of incomitant strabismus. Anomalous innervation to extraocular
      muscles can result in a wide variety of phenotypes causing various clinical
      conditions such as Duane syndrome, congenital fibrosis of the extraocular
      muscles, and Mobius syndrome. We report a case of bilateral dysinnervation
      disorder causing atypical ocular movements in both eyes as the patient changes
      fixation from one eye to the other and from right gaze to left gaze that fits
      with the wider diagnosis of CCDDs.

PMID- 29643790
TI  - A Case of Fundus Oculi Albinoticus Diagnosed as Angelman Syndrome by Genetic
      Testing.
AB  - Purpose: To report a case of fundus oculi albinoticus diagnosed as Angelman
      syndrome (AS) via genetic testing. Case Report: This study reports on a 4-year
      old boy. Since he had been having respiratory disturbance since birth, he
      underwent a complete physical examination to investigate the cause. The results
      indicated that he had various brain congenital abnormalities, such as a thin
      corpus callosum, as well as hydronephrosis, an atrial septal defect, and skin
      similar to patients with fundus oculi albinoticus. Examination revealed bilateral
      fundus oculi albinoticus, mild iridic hypopigmentation, optic atrophy, and poor
      visual tracking. Genetic testing revealed a deletion in the Prader-Willi
      syndrome/AS region on chromosome 15, and together with the results of methylation
      analysis, his condition was diagnosed as AS. Follow-up examinations revealed no
      change in the fundus oculi albinoticus and optic atrophy, nor did they indicate
      poor visual tracking. Conclusions: When fundus oculi albinoticus and optic
      atrophy are observed in patients with multiple malformations, AS should be
      considered as a differential diagnosis.

PMID- 29643791
TI  - Autologous Transplantation of the Internal Limiting Membrane for Refractory
      Macular Hole following Ruptured Retinal Arterial Macroaneurysm: A Case Report.
AB  - Purpose: To report a case of macular hole (MH) secondary to a retinal arterial
      macroaneurysm (RAMA) which was successfully treated with an autologous
      transplantation of internal limiting membrane (ILM). Case Report: An 87-year-old
      female presented with a sudden decrease in central vision in the right eye. A
      fundus examination revealed a RAMA in the superonasal macular region, a
      subretinal hemorrhage (SRH), involving the macula, and a sub-ILM hemorrhage. A
      pars plana vitrectomy (PPV) was performed. Intraoperatively, an MH filled with
      coagulum was detected. We tried to blow off and drain the SRH with a current of
      BSS and a gentle suction with a 27-gauge vitreous cutter from the MH, but some
      amount of SRH at the bottom of the MH remained. The ILM was peeled off for 2 disc
      diameters around the MH. The vitreous cavity was filled with air at the end of
      the operation. Two weeks after the surgery, the MH was not closed. One month
      following the initial PPV, a second PPV was performed to achieve closure of the
      MH. Results: An autologous transplantation of ILM was performed as second PPV.
      Six months after the final surgery, the MH was successfully closed and the best
      corrected decimal visual acuity was 0.6. Conclusions: Autologous ILM
      transplantation can be an effective treatment option for MH closure following
      RAMA rupture.

PMID- 29643792
TI  - A Case of Neurotrophic Keratopathy Associated with Nasopharyngeal Carcinoma.
AB  - Purpose: To report a case of neurotrophic keratopathy associated with
      nasopharyngeal carcinoma. Case Report: A 59-year-old man who had been diagnosed
      with a nasopharyngeal carcinoma was referred to the authors because of visual
      disturbance and pain in his right eye. Slit-lamp examination revealed a corneal
      epithelial defect and corneal stromal edema surrounding the epithelial defect
      area in his right eye. Magnetic resonance imaging showed a mass in his cavernous
      sinus, which was identified as nasopharyngeal carcinoma (NPC). We diagnosed
      neurotrophic keratopathy associated with NPC and initiated treatment with
      preservative-free artificial tears, antibiotic eye drops, fibronectin, a
      therapeutic contact lens, and amniotic membrane transplantation. However, the
      persistent corneal epithelial defect was unresponsive to these treatments.
      Conclusion: Neurotrophic keratopathy secondary to NPC is thought to be rare. We
      presented a case of neurotrophic keratopathy associated with cavernous sinus
      metastasis of an NPC. The development of new and more effective treatments for
      this refractory disease is anticipated.

PMID- 29643793
TI  - Central Serous Chorioretinopathy Associated with Desmopressin Nasal Spray:
      Causality or Unfortunate Association.
AB  - Purpose: To describe the possible association between central serous
      chorioretinopathy (CSCR) and desmopressin use. Methods: The case histories of 2
      middle-aged men with CSCR using desmopressin nasal spray were studied. Results:
      The diagnosis of CSCR was made on the basis of clinical features and ancillary
      testing (fluorescein angiography and optical coherence tomography). Both patients
      were using desmopressin nasal spray for polyuria when they developed the first
      ocular symptoms. Both of them also had an independent risk factor for developing
      CSCR. Conclusion: We suggest that desmopressin-induced hypercortisolism might
      implicate the development of CSCR in some patients. A larger study on patients
      using desmopressin nasal spray would be beneficial to confirm the possible
      association between this form of therapy and the development of CSCR.

PMID- 29643794
TI  - Isolated Medial Orbital Wall Fracture Associated with Enophthalmos in a
      Paediatric Patient: An Unusual Presentation.
AB  - Purpose: To report a case of isolated medial orbital wall fracture with
      enophthalmos in a paediatric patient and describe the clinical presentation and
      findings by means of computed tomography (CT) of the head and eyes. Methods: We
      looked at the patient's medical and ophthalmologic history, and an ophthalmologic
      examination and a CT of the head were performed at baseline. Results: A 14-year
      old boy was admitted to the emergency department of our institution with
      ecchymosis of his right eyelids secondary to a sport accident. Physical
      examination revealed a moderate limitation of upgaze without diplopia. CT showed
      a medial orbital wall fracture without haemorrhage and a gross accumulation of
      air in the right eyelid with pressure exertion over the right globe and
      enophthalmos. The patient was treated conservatively with oral antibiotics and
      steroids showing dramatic improvement within 1 week. Enophthalmos and periorbital
      emphysema were completely resolved within 3 months after the accident as
      indicated by CT. Conclusions: We conclude that surgical intervention and
      intravenous treatment are not warranted in similar cases of medial orbital wall
      fracture. Medical history, clinical and paraclinical evaluations, and a regular
      follow-up, including CT, are needed though to avoid complications such as painful
      abduction, horizontal diplopia, pseudo sixth nerve paresis, or pseudo Duane.

PMID- 29643795
TI  - Ocular Injury due to Potassium Permanganate Granules.
AB  - Purpose: We report a rare case of ocular injury due to potassium permanganate
      (KMnO4) granules in a child. Methods: This is a retrospective case report.
      Results: A 2-year-old boy was transferred to our emergency room with severe pain
      in his right eye, inflamed eyelids, and brownish stains on his fingers. Chemical
      injury was suspected. Copious eye irrigation was immediately performed. Diffuse
      brownish splotches were then observed at the inferior bulbar conjunctiva.
      Otherwise, systemic organs were intact. Complete eye exam under general
      anesthesia revealed a 5-mm epithelial defect at the central cornea, along with
      generalized conjunctival injection and limbal ischemia, inferiorly. Multiple semi
      dissolved granules of KMnO4 trapped in the inferior fornix were identified. The
      chemical particles were gradually washed out and removed; however, the brownish
      stains remained. The patient received preservative-free steroid, antibiotic eye
      drops, and lubricants as regular management for mild to moderate degree of ocular
      burn. Pseudomembrane developed early and transformed into symblepharon within a
      few days after the injury. Membrane adhesion was lysed, and more aggressive
      medications were then substituted. Commercial amniotic membrane (PROKERA(r)) was
      also applied to promote wound healing and to prevent recurrence of symblepharon.
      The ocular surface was eventually restored, and corneal transparency was
      preserved. Conclusion: Ocular injury with the granular form of KMnO4 is rare. Its
      toxicity is comparable to concentrated KMnO4 solution. However, the dissolved
      particles that had been absorbed in the stained conjunctiva were continuously
      released and damaged the ocular surface more than we primarily anticipated.
      Awareness of this condition and prompt management yield a good treatment outcome.

PMID- 29643796
TI  - A Rare Form of Corneal Opacity Associated with Spondyloepiphyseal Dysplasia
      Congenita.
AB  - A 13-year-old Japanese female diagnosed with spondyloepiphyseal dysplasia
      congenita (SEDC) was referred for ophthalmologic evaluation. Examination with
      slit-lamp and optical coherence tomography revealed bilateral thin cornea with
      diffuse corneal opacity which was localised at the posterior stromal depth in the
      central cornea. Unlike the two previously reported cases of diffuse and nodular
      patterns of corneal opacity in SEDC, the current case exhibited a rare form of
      corneal opacity. SEDC is one of the type II collagenopathies, characterised by
      dwarfism because the mutations in COL2A1 prevent bone growth. Although the
      existence of type II collagen has not been reported in the human corneal stroma,
      the aetiology of the opacity in the corneal stroma in SEDC type II collagenopathy
      is of interest.

PMID- 29643797
TI  - Uneventful Anterior Migration of Intravitreal Ozurdex Implant in a Patient with
      Iris-Sutured Intraocular Lens and Descemet Stripping Automated Endothelial
      Keratoplasty.
AB  - Purpose: We report here the case of a patient with anterior segment migration of
      intravitreal dexamethasone implant as well as its management and outcome.
      Methods: The patient had the following sequence of events: complicated cataract
      surgery, iris-sutured intraocular lens implant, followed by cystoid macular edema
      treated with intravitreal Avastin, retinal vein occlusion treated with
      intravitreal dexamethasone implant, corneal decompensation treated with Descemet
      stripping automated endothelial keratoplasty (DSAEK), and finally recurrence of
      macular edema treated with repeated intravitreal dexamethasone implant. Results:
      Dexamethasone implant had completely dissolved from the eye 12 weeks after
      insertion without any complication. Conclusion: A conservative approach with
      regular monitoring in the situation of a quiet anterior segment without any
      corneal decompensation can provide enough time for the implant to dissolve
      without causing any complication to the involved eye, avoiding any additional
      surgical intervention, as presented in this case report. Despite the fact that
      the implant was left for natural dissolution, there were no adverse effects
      related to the graft or the eye.

PMID- 29643798
TI  - Rapid Capsular Contraction with Secondary Intraocular Lens Dislocation Associated
      with Unspecified Rod-Cone Dystrophy: A Case Report.
AB  - Purpose: We report an unusual case of rapid and severe anterior capsular
      contraction associated with secondary intraocular lens (IOL) dislocation
      following cataract surgery in a patient with unspecified rod-cone dystrophy. Case
      Report: A 68-year-old woman with a history of uncharacterized bilateral rod-cone
      dystrophy presented with blurry vision 1 month after cataract surgery. Best
      corrected visual acuity was 20/40 in the operative eye. Slit-lamp exam showed
      severe anterior capsular phimosis limiting view of the fundus. Our patient
      underwent 2 sessions of Nd:YAG anterior capsulotomy with limited success. Limited
      anterior vitrectomy was then performed without success due to densely adherent
      capsular tissue to the anterior surface of the IOL and additional secondary IOL
      dislocation. She ultimately underwent pars plana vitrectomy, removal of the
      capsular bag, and IOL exchange with a scleral fixated IOL. Conclusion: Rapid and
      severe anterior capsular contraction following cataract surgery is rare but
      appears to be associated with rod-cone dystrophy.

PMID- 29643799
TI  - Optical Coherence Tomography Examination of the Anterior Segment in a Case of
      Corneal Perforation and Lens Trauma by Chestnut Burr.
AB  - Chestnut burrs, the thorny encapsulation of chestnut fruit, can sometimes cause
      corneal injuries and ulceration, with poor prognoses. We report a case of corneal
      perforation and damaged anterior lens capsule due to a chestnut burr, using
      anterior segment optical coherence tomography (AS-OCT). A 67-year-old woman with
      a chestnut burr injury in her right eye was referred to our hospital. Her right
      best-corrected visual acuity (BCVA) was 0.8. Slit-lamp examination and AS-OCT
      showed perforation involving the endothelial layer at the center of the cornea.
      The iris and anterior lens capsule were damaged. Cell infiltration was observed
      around the wound. Bacterial examination showed gram-positive cocci but no fungi.
      The patient was diagnosed with a corneal perforation and bacterial keratitis.
      Levofloxacin 1.5% and cefmenoxime treatments were initiated and a soft contact
      lens was placed to seal the wound. On day 3, there was no improvement in the
      corneal cell infiltration, but AS-OCT suggested that the inner wound had closed.
      A culture test revealed the presence of Propionibacterium acnes, which was
      sensitive to both levofloxacin and cefmenoxime. Therefore, we continued the same
      antibiotic treatment. On day 26, the opacification and cell infiltration at the
      center of the cornea had improved. AS-OCT showed healing of the corneal wound
      with reduction in the central corneal thickness. Her BCVA improved to 1.0. AS-OCT
      was a valuable tool to noninvasively observe wound shape and detect the presence
      of any intracorneal foreign bodies.

PMID- 29643800
TI  - Interaction of Norepinephrine and Glucocorticoids Modulate Inhibition of
      Principle Cells of Layer II Medial Entorhinal Cortex in Male Mice.
AB  - Spatial memory processing requires functional interaction between the hippocampus
      and the medial entorhinal cortex (MEC). The grid cells of the MEC are most
      abundant in layer II and rely on a complex network of local inhibitory
      interneurons to generate spatial firing properties. Stress can cause spatial
      memory deficits in males, but the specific underlying mechanisms affecting the
      known memory pathways remain unclear. Stress activates both the autonomic nervous
      system and the hypothalamic-pituitary-adrenal axis to release norepinephrine (NE)
      and glucocorticoids, respectively. Given that adrenergic receptor (AR) and
      glucocorticoid receptor (GR) expression is abundant in the MEC, both
      glucocorticoids and NE released in response to stress may have rapid effects on
      MEC-LII networks. We used whole-cell patch clamp electrophysiology in MEC slice
      preparations from male mice to test the effects of NE and glucocorticoids on
      inhibitory synaptic inputs of MEC-LII principal cells. Application of NE (100
      MUM) increased the frequency and amplitude of spontaneous inhibitory post
      synaptic currents (sIPSCs) in approximately 75% of the principal cells tested.
      Unlike NE, bath application of dexamethasone (Dex, 1 MUM), a synthetic
      glucocorticoid, or corticosterone (1 MUM) the glucocorticoid in rodents, rapidly
      decreased the frequency of sIPSCs, but not miniature (mIPSCs) in MEC-LII
      principal cells. Interestingly, pre-treatment with Dex prior to NE application
      led to an NE-induced increase in sIPSC frequency in all cells tested. This effect
      was mediated by the alpha1-AR, as application of an alpha1-AR agonist,
      phenylephrine (PHE) yielded the same results, suggesting that a subset of cells
      in MEC-LII are unresponsive to alpha1-AR activation without prior activation of
      GR. We conclude that activation of GRs primes a subset of principal cells that
      were previously insensitive to NE to become responsive to alpha1-AR activation in
      a transcription-independent manner. These findings demonstrate the ability of
      stress hormones to markedly alter inhibitory signaling within MEC-LII circuits
      and suggest the intriguing possibility of modulation of network processing
      upstream of the hippocampus.

PMID- 29643801
TI  - Prevalence of and Risk Factors for Cognitive Impairment Among Elderly Without
      Cardio- and Cerebrovascular Diseases: A Population-Based Study in Rural China.
AB  - This study aimed to evaluate the prevalence of cognitive impairment and the
      distribution of its risk factors among residents aged >=60 years without
      cardiovascular and cerebrovascular diseases in rural areas of northern China
      screened with the Chinese version of the Mini-Mental State Examination (MMSE).
      Between 2012 and 2013, a questionnaire survey was conducted to collect basic
      information from participants. Cognitive function was assessed using the MMSE. In
      the univariate analysis, risk factors for cognitive disorders were female sex,
      low education and central obesity, while drinking was found to be a protective
      factor. In the multivariate analysis, risk factors were old age (odds ratio [OR],
      1.888; 95% confidence interval [CI]: 1.256-2.838; P = 0.002 for the 70-year-old
      group compared with the 60-year-old group; OR, 3.593; 95% CI, 2.468-5.230; P <
      0.001 for the >=75-year-old group compared with the 60-year-old group), low
      education (OR, 3.779; 95% CI: 2.218-6.440; P < 0.001 for the illiterate group
      compared with the group with >=9 years of education; OR, 1.667; 95% CI, 1.001
      2.775; P = 0.05 for the group with less than primary school compared with the
      group with >=9 years of education), and higher blood pressure (BP; OR, 1.655; 95%
      CI: 1.076-2.544; P = 0.002 for individuals with stage III hypertension compared
      with those with normal BP). These findings suggest that it is crucial to manage
      and control level of BP, and improve educational attainment in order to reduce
      the prevalence and burden of cognitive impairment among low-income residents in
      rural China.

PMID- 29643804
TI  - NSAID Exposure and Risk of Alzheimer's Disease: An Updated Meta-Analysis From
      Cohort Studies.
AB  - Background: Initial observational studies and a systematic review published
      recently have suggested that non-steroidal anti-inflammatory drug (NSAID) use has
      the trend to be associated with reduced risk of Alzheimer's disease (AD), while
      results remain conflicting. Thus, we performed an updated meta-analysis to
      reevaluate the evidence on this association. Methods: Data sources from PUBMED,
      Embase and Cochrane Library from inception through April 2017 were searched by
      two independent reviewers. Eligible cohort studies were selected according to
      predefined keywords. We did a meta-analysis of available study data using a
      random-effects model to calculate overall relative risks (RRs) for associations
      between NSAID exposure and AD risk. Results: From 121 potentially relevant
      studies, 16 cohort studies including 236,022 participants, published between 1995
      and 2016, were included in this systematic review. Meta-analysis demonstrated
      that current or former NSAID use was significantly associated with reduced risk
      of AD (RR, 0.81, 95% CI0.70 to 0.94) compared with those who did not use NSAIDs.
      This association existed in studies including all NSAID types, but not in aspirin
      (RR, 0.89, 95% CI 0.70 to 1.13), acetaminophen (RR, 0.87, 95% CI 0.40 to 1.91) or
      non-aspirin NSAID (RR, 0.84, 95% CI 0.58 to 1.23). Conclusions: Current evidence
      suggests that NSAID exposure might be significantly associated with reduced risk
      of AD. However, further large-scale prospective studies are needed to reevaluate
      this association, especially the associations in individual NSAID type.

PMID- 29643803
TI  - Association Between MicroRNAs Polymorphisms and Risk of Ischemic Stroke: A Meta
      Analysis in Chinese Individuals.
AB  - Objective: Previous studies have demonstrated that some single-nucleotide
      polymorphisms (SNPs) in miRNAs are related to the risk of ischemic stroke (IS),
      but the conclusions are still controversial and inconclusive. We performed this
      meta-analysis to further assess the association between miR-146a C>G (rs2910164),
      miR-149 T>C (rs2292832), miR-196a2 T>C (rs11614913), miR-499 A>G (rs3746444) and
      risk of IS in Chinese individuals. Methods: Relevant studies were identified in
      the databases of PubMed, Embase. The strength of correlation between microRNAs
      polymorphisms and IS risk was assessed by odds ratios (ORs) and 95% confidence
      intervals (95% CIs) under five genetic models. Results: 5 studies, containing
      2,632 cases and 3,191 controls, were included in this meta-analysis. The overall
      results of meta-analysis indicated that there were no significant association
      between miR-146a C>G (rs2910164), miR-149 T>C (rs2292832), miR-196a2 T>C
      (rs11614913), and the IS risk in the overall analyses. MiR-499 A>G (rs3746444)
      was associated with an increased IS risk under allele model (OR = 1.30, 95% CI =
      1.02-1.66), heterozygous model (OR = 1.35, 95% CI = 1.01-1.79) and dominant model
      (OR = 1.36, 95% CI = 1.02-1.80) in Chinese. The sensitivity analysis results of
      these four polymorphisms were similar to the overall results. Conclusion: MiR-499
      A>G (rs3746444) G allele and AG, AG + AA genotype might be risk factors of IS in
      Chinese. No significant association was observed between miR-146a C>G
      (rs2910164), miR-149 T>C (rs2292832), miR-196a2 T>C (rs11614913), and IS risk.
      The associations may be different due to geographical factors of China. More
      explorations in more diverse geographically regions with large sample size are
      expected to further verify the findings in the future.

PMID- 29643802
TI  - The Beneficial Effects of Cognitive Training With Simple Calculation and Reading
      Aloud (SCRA) in the Elderly Postoperative Population: A Pilot Randomized
      Controlled Trial.
AB  - Background: There has been little research conducted regarding cognitive
      treatments for the elderly postsurgical population. Patients aged >=60 years have
      an increased risk of postoperative cognitive decline, a condition in which
      cognitive functions are negatively affected. This cognitive decline can lead to a
      decline in quality of life. In order to maintain a high quality of life, the
      elderly postsurgical population may benefit from treatment to maintain and/or
      improve their cognitive functions. This pilot study investigates the effect of
      simple calculation and reading aloud (SCRA) cognitive training in elderly
      Japanese postsurgical patients. Methods: Elderly patients undergoing non
      cardiovascular thoracic surgery under general anesthesia were recruited (n = 12).
      Subjects were randomly divided into two groups-one that receives 12 weeks of SCRA
      intervention, and a waitlisted control group. Before and after the intervention,
      we measured cognitive function [Mini-Mental Status Exam-Japanese (MMSE-J),
      Frontal Assessment Battery (FAB), computerized Cogstate Brief Battery (CBB)] and
      emotional state [General Health Questionnaire-12 (GHQ-12), Geriatric Depression
      Scale (GDS), Quality of Life Scale-5 (QOL-5)]. Results: Group difference analyses
      using ANCOVA with permutation test showed that the intervention SCRA group had a
      significant improvement in FAB motor programming sub-score, GDS, and QOL-5
      compared to the control group. Within-group analyses using Wilcoxon signed-rank
      test to compare baseline and follow-up showed that the SCRA intervention group
      total FAB scores, FAB motor programming sub-scores, and QOL-5 scores were
      significantly improved. Discussion: This pilot study showed that there are
      important implications for the beneficial effects of SCRA intervention on
      cognitive function and emotional state in the postoperative elderly population;
      however, further investigations are necessary to reach any conclusions. Trial
      registration: This study was registered with the University Hospital Medical
      Information Network (UMIN) Clinical Trial Registry (UMIN000019832).

PMID- 29643805
TI  - Deviation of Spatial Representation and Asymmetric Saccadic Reaction Time in Hemi
      Parkinson's Disease.
AB  - Background: Patients with Parkinson's disease (PD) commonly show spatially
      asymmetric behaviors, such as veering while attempting to walk in a straight
      line. While there is general agreement that the lateral motor dysfunction
      contributes to asymmetric behaviors in PD, it is dispute regarding whether the
      spatial perception is also biased. In addition, it is not clear whether PD
      impairs the speed of spatial information process, i.e., the efficiency of
      information process. Objectives: To assess the visuospatial representation and
      efficiency of spatial information processing in hemi-PD. Methods: Two saccadic
      tasks were employed: non-spatial cue evoked saccade and spatial cue evoked
      saccade. In the former task, an identical visual stimulus (appeared on the body
      mid-sagittal plane) was artificially associated with a fixed saccadic target
      (left or right) in a given session. In the latter task, subjects were instructed
      to make a rightward or leftward saccade based on the perceived location of a
      visual cue (left vs. right side of the body mid-sagittal plane). We estimated the
      location of subjective straight ahead (SSA) for each subject by using a
      psychometric fitting function to fit the location judgment results, enabling
      evaluation of the symmetry of representation between the left and right
      hemifields. In addition, since the locations of saccadic targets were same in
      these two tasks, thus, for each individual subject, the elongated saccadic
      reaction time (SRT) in the latter task, comparing with the former one, mainly
      reflects the time spent on judgment of the spatial location of visual cue, i.e.,
      spatial perception. We also assessed the efficiency of spatial perception between
      two hemispheres, through comparing the normalized SRT (i.e., SRT difference
      between two tasks) between trials with leftward and rightward judgments. Results:
      Compared with healthy control subjects (HCs), the SSA was shifted to the
      contralesional side in both left onset PD (LPD, lesion of right substantia nigra)
      and right onset PD (RPD, lesion of left substantia nigra) patients. The process
      of spatial information was significantly longer when a spatial cue appeared in
      the contralesional hemifield. Conclusions: Patients with hemi-PD showed biased
      visuospatial representation between left and right hemifields and decreased the
      efficiency of spatial information processing in the contralesional side. Such
      results indicate that the hemi-PD impairs both spatial representation and the
      efficiency of spatial information process, which might contribute to asymmetric
      behaviors.

PMID- 29643806
TI  - Diverged Effects of Piperine on Testicular Development: Stimulating Leydig Cell
      Development but Inhibiting Spermatogenesis in Rats.
AB  - Background: Piperine is the primary pungent alkaloid isolated from the fruit of
      black peppercorns. Piperine is used frequently in dietary supplements and
      traditional medicines. The objective of the present study was to investigate the
      effects of piperine on the testis development in the pubertal rat. Methods:
      Piperine (0 or 5 or 10 mg/kg) was gavaged to 35-day-old male Sprague-Dawley rats
      for 30 days. Serum levels of testosterone (T), luteinizing hormone (LH), and
      follicle-stimulating hormone (FSH) were measured. The development of adult Leydig
      cell population was also analyzed 65 days postpartum. For in vitro studies,
      immature Leydig cells were isolated from 35-day-old male rats and treated with 50
      MUM piperine in the presence of different steroidogenic stimulators/substrates
      for 24 h. Results: Thirty-day treatment of rats with piperine significantly
      increased serum T levels without affecting LH concentrations. However, piperine
      treatment reduced serum FSH levels. Consistent with increase in serum T, piperine
      increased Leydig cell number, cell size, and multiple steroidogenic pathway
      proteins, including steroidogenic acute regulatory protein, cholesterol side
      chain cleavage enzyme, 3beta-hydroxysteroid dehydrogenase 1, 17alpha
      hydroxylase/20-lyase, and steroidogenic factor 1 expression levels. Piperine
      significantly increased the ratio of phospho-AKT1 (pAKT1)/AKT1, phosphos-AKT2
      (pAKT2)/AKT2, and phospho-ERK1/2 (pERK1/2)/ERK1/2 in the testis. Interestingly,
      piperine inhibited spermatogenesis. Piperine in vitro also increased androgen
      production and stimulated cholesterol side-chain cleavage enzyme and 17alpha
      hydroxylase/20-lyase activities in immature Leydig cells. Conclusion: Piperine
      stimulates pubertal Leydig cell development by increasing Leydig cell number and
      promoting its maturation while it inhibits spermatogenesis in the rat. ERK1/2 and
      AKT pathways may involve in the piperine-mediated stimulation of Leydig cell
      development.

PMID- 29643808
TI  - Innovative Nanoparticles Enhance N-Palmitoylethanolamide Intraocular Delivery.
AB  - Nanostructured lipid carriers (NLCs) loaded with palmitoylethanolamide (PEA) were
      formulated with the aim to enhance ocular bioavailability of PEA, particularly to
      the back of the eye. Technological characterization (e.g., size, charge) of NLC
      loaded with PEA formulation (PEA-NLC) was performed, and NLC morphology was
      characterized by electron microscopy. Ocular pharmacokinetic study, after topical
      administration of the formulation, was carried out in rabbit eye. Ultra-high
      performance liquid chromatography tandem mass spectrometry analysis was carried
      out to detect PEA levels in ocular tissues. Finally, the ocular tolerability of
      PEA-NLC formulation was assessed in rabbit eye. The novel formulation
      significantly increased PEA levels in ocular tissues compared to PEA suspension.
      Vitreous and retinal levels of PEA were significantly higher in the group treated
      with PEA-NLC formulation versus PEA suspension (PEA-NLC Cmax 5919 +/- 541 pmol/g
      and 315 +/- 70 pmol/g in vitreous and retina, respectively). The PEA-NLC
      formulation was characterized by high stability and robust ocular
      bioavailability. Therefore, this innovative formulation may be useful in clinical
      practice to manage retinal diseases.

PMID- 29643809
TI  - Examination of the Role of Mitochondrial Morphology and Function in the
      Cardioprotective Effect of Sodium Nitrite Administered 24 h Before
      Ischemia/Reperfusion Injury.
AB  - Background: We have previous evidence that in anesthetized dogs the inorganic
      sodium nitrite protects against the severe ventricular arrhythmias, resulting
      from coronary artery occlusion and reperfusion, when administered 24 h before.
      The present study aimed to examine, whether in this effect changes in
      mitochondrial morphology and function would play a role. Methods: Thirty dogs
      were infused intravenously either with saline (n = 15) or sodium nitrite (0.2
      MUmol/kg/min; n = 15) for 20 min, and 24 h later, 10 dogs from each group were
      subjected to a 25 min period of occlusion and then reperfusion of the left
      anterior descending coronary artery. The severity of ischaemia and ventricular
      arrhythmias were examined in situ. Left ventricular tissue samples were collected
      either before the occlusion (5 saline and 5 nitrite treated dogs) or, in dogs
      subjected to occlusion, 2 min after reperfusion. Changes in mitochondrial
      morphology, in complex I and complex II-dependent oxidative phosphorylation
      (OXPHOS), in ATP, superoxide, and peroxynitrite productions were determined.
      Results: The administration of sodium nitrite 24 h before ischemia/reperfusion
      significantly attenuated the severity of ischaemia, and markedly reduced the
      number and incidence of ventricular arrhythmias. Nitrite also attenuated the
      ischaemia and reperfusion (I/R)-induced structural alterations, such as
      reductions in mitochondrial area, perimeter, and Feret diameter, as well as the
      increase in mitochondrial roundness. The administration of nitrite, however,
      enhanced the I/R-induced reduction in the mitochondrial respiratory parameters;
      compared to the controls, 24 h after the infusion of nitrite, there were further
      significant decreases, e.g., in the complex I-dependent OXPHOS (by -20 vs. -53%),
      respiratory control ratio (by -14 vs. -61%) and in the P/E control coupling ratio
      (by 2 vs. -36%). Nitrite also significantly reduced the I/R-induced generation of
      superoxide, without substantially influencing the ATP production. Conclusions:
      The results suggest that sodium nitrite may have an effect on the mitochondria;
      it preserves the mitochondrial structure and modifies the mitochondrial function,
      when administered 24 h prior to I/R. We propose that nitrite affects primary the
      phosphorylation system (indicated by the decreased P/E ratio), and the reduction
      in superoxide production would result from the subsequent suppression of the ROS
      producing complexes; an effect which may certainly contribute to the
      antiarrhythmic effect of nitrite.

PMID- 29643810
TI  - Localized Delivery of Cl-Amidine From Electrospun Polydioxanone Templates to
      Regulate Acute Neutrophil NETosis: A Preliminary Evaluation of the PAD4 Inhibitor
      for Tissue Engineering.
AB  - Upon interaction, neutrophils can potentially release neutrophil extracellular
      traps (NETs) on the surface of an implanted electrospun template, which may be a
      significant preconditioning event for implantable biomaterials of yet unknown
      consequences. In this study, we investigated the potential of polydioxanone
      templates as a delivery vehicle for Cl-amidine, an inhibitor of peptidyl arginase
      deiminase 4 (PAD4), and if drug elution could attenuate PAD4-mediated NETosis in
      the vicinity of implanted templates. Electrospun polydioxanone templates were
      fabricated with distinct architectures, small diameter (0.4 MUm) or large
      diameter (1.8 MUm) fibers, and incorporated with 0-5 mg/mL Cl-amidine to examine
      dose-dependent effects. Acute neutrophil-template interactions were evaluated in
      vitro with freshly isolated human neutrophils and in vivo with a rat subcutaneous
      implant model. The in vitro results suggest large diameter templates with 0 mg/mL
      Cl-amidine significantly attenuate NETosis compared to small diameter templates.
      As the drug concentration increased, NETosis was significantly decreased on small
      diameter templates in a dose-dependent manner. The opposite was observed for
      large diameter templates, indicating multiple mechanisms of NETosis may be
      regulating neutrophil template preconditioning. Similar results were observed in
      vivo, verifying local NETosis inhibition by Cl-amidine eluting templates in a
      physiological environment. Importantly, large diameter templates with Cl-amidine
      enhanced neutrophil invasion and survival, supporting the potential for long-term
      modulation of tissue integration and regeneration. This preliminary study
      demonstrates a novel delivery vehicle for Cl-amidine that can be used to regulate
      acute NETosis as the potential critical link between the innate immune response,
      inflammation, and template-guided tissue regeneration.

PMID- 29643811
TI  - Pristimerin as a Novel Hepatoprotective Agent Against Experimental Autoimmune
      Hepatitis.
AB  - Pristimerin (Pris) is bioactive natural quinonoid triterpene that has anti
      inflammatory and anti-cancer activities. Meanwhile, its effect against hepatitis
      needs to be elucidated. This investigation aimed to evaluate the ability of Pris
      to protect against autoimmune hepatitis (AIH). A mouse model of AIH was
      established using single concanavalin A (Con A) intravenous injection. Mice were
      treated with Pris at two different doses (0.4 and 0.8 mg/kg) for 5 days prior to
      Con A challenge. Markers of hepatic injury, oxidative, inflammatory, and
      apoptotic damage were estimated. Results have revealed that Pris pretreatment
      ameliorated Con A-induced hepatic damage. There was decrease in the elevated
      serum indices of hepatic damage (ALT, AST, ALP, and LDH) and improvement of the
      histopathological picture of the liver. Pris effectively decreased Con A-induced
      neutrophil infiltration into the hepatic tissue as presented by amelioration of
      the level and immuno-expression of myeloperoxidase (MPO). Additionally, Pris
      attenuated Con A-induced increase in CD4+ T-cells in hepatic tissue. Lipid
      peroxidation was significantly depressed simultaneously with enhancement of the
      antioxidant capacity in Pris pretreated animals. Pris also enhanced nuclear
      factor erythroid 2-related factor 2 (Nrf2) mRNA expression and its binding
      capacity. In addition, Pris increased mRNA expression of heme-oxygenase-1 (HO-1)
      and restored its normal level. Furthermore, Pris decreased the level and immuno
      expression of nuclear factor kappa-B (NF-kappaB) as well as the downstream
      inflammatory cascade (TNF-alpha, IL-6, and IL-1beta). Finally, Pris showed
      inhibitory effect on Con A-induced apoptotic alteration in liver as it decreased
      the mRNA expression and levels the apoptotic markers (Bax and caspase-3) and
      increased mRNA expression and level of the anti-apoptotic protein (Bcl2). In
      conclusion, this study demonstrates the potent hepatoprotective efficacy of Pris
      against Con A-induced hepatitis which may be related to anti-oxidative, anti
      inflammatory, and anti-apoptotic pathways. Pris could serve as a new candidate
      for the management of hepatitis.

PMID- 29643807
TI  - Antimicrobial Peptides and Their Therapeutic Potential for Bacterial Skin
      Infections and Wounds.
AB  - Alarming data about increasing resistance to conventional antibiotics are
      reported, while at the same time the development of new antibiotics is
      stagnating. Skin and soft tissue infections (SSTIs) are mainly caused by the so
      called ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella
      pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter
      species) which belong to the most recalcitrant bacteria and are resistant to
      almost all common antibiotics. S. aureus and P. aeruginosa are the most frequent
      pathogens isolated from chronic wounds and increasing resistance to topical
      antibiotics has become a major issue. Therefore, new treatment options are
      urgently needed. In recent years, research focused on the development of
      synthetic antimicrobial peptides (AMPs) with lower toxicity and improved activity
      compared to their endogenous counterparts. AMPs appear to be promising
      therapeutic options for the treatment of SSTIs and wounds as they show a broad
      spectrum of antimicrobial activity, low resistance rates and display pivotal
      immunomodulatory as well as wound healing promoting activities such as induction
      of cell migration and proliferation and angiogenesis. In this review, we evaluate
      the potential of AMPs for the treatment of bacterial SSTIs and wounds and provide
      an overview of the mechanisms of actions of AMPs that contribute to combat skin
      infections and to improve wound healing. Bacteria growing in biofilms are more
      resistant to conventional antibiotics than their planktonic counterparts due to
      limited biofilm penetration and distinct metabolic and physiological functions,
      and often result in chronification of infections and wounds. Thus, we further
      discuss the feasibility of AMPs as anti-biofilm agents. Finally, we highlight
      perspectives for future therapies and which issues remain to bring AMPs
      successfully to the market.

PMID- 29643812
TI  - Left Ventricular Wall Stress Is Sensitive Marker of Hypertrophic Cardiomyopathy
      With Preserved Ejection Fraction.
AB  - Hypertrophic cardiomyopathy (HCM) patients present altered myocardial mechanics
      due to the hypertrophied ventricular wall and are typically diagnosed by the
      increase in myocardium wall thickness. This study aimed to quantify regional left
      ventricular (LV) shape, wall stress and deformation from cardiac magnetic
      resonance (MR) images in HCM patients and controls, in order to establish
      superior measures to differentiate HCM from controls. A total of 19 HCM patients
      and 19 controls underwent cardiac MR scans. The acquired MR images were used to
      reconstruct 3D LV geometrical models and compute the regional parameters (i.e.,
      wall thickness, curvedness, wall stress, area strain and ejection fraction) based
      on the standard 16 segment model using our in-house software. HCM patients were
      further classified into four quartiles based on wall thickness at end diastole
      (ED) to assess the impact of wall thickness on these regional parameters. There
      was a significant difference between the HCM patients and controls for all
      regional parameters (P < 0.001). Wall thickness was greater in HCM patients at
      the end-diastolic and end-systolic phases, and thickness was most pronounced in
      segments at the septal regions. A multivariate stepwise selection algorithm
      identified wall stress index at ED (sigma i,ED ) as the single best independent
      predictor of HCM (AUC = 0.947). At the cutoff value sigma i,ED < 1.64, both
      sensitivity and specificity were 94.7%. This suggests that the end-diastolic wall
      stress index incorporating regional wall curvature-an index based on mechanical
      principle-is a sensitive biomarker for HCM diagnosis with potential utility in
      diagnostic and therapeutic assessment.

PMID- 29643813
TI  - Skull Development, Ossification Pattern, and Adult Shape in the Emerging Lizard
      Model Organism Pogona vitticeps: A Comparative Analysis With Other Squamates.
AB  - The rise of the Evo-Devo field and the development of multidisciplinary research
      tools at various levels of biological organization have led to a growing interest
      in researching for new non-model organisms. Squamates (lizards and snakes) are
      particularly important for understanding fundamental questions about the
      evolution of vertebrates because of their high diversity and evolutionary
      innovations and adaptations that portrait a striking body plan change that
      reached its extreme in snakes. Yet, little is known about the intricate
      connection between phenotype and genotype in squamates, partly due to limited
      developmental knowledge and incomplete characterization of embryonic development.
      Surprisingly, squamate models have received limited attention in comparative
      developmental studies, and only a few species examined so far can be considered
      as representative and appropriate model organism for mechanistic Evo-Devo
      studies. Fortunately, the agamid lizard Pogona vitticeps (central bearded dragon)
      is one of the most popular, domesticated reptile species with both a well
      established history in captivity and key advantages for research, thus forming an
      ideal laboratory model system and justifying his recent use in reptile biology
      research. We first report here the complete post-oviposition embryonic
      development for P. vitticeps based on standardized staging systems and external
      morphological characters previously defined for squamates. Whereas the overall
      morphological development follows the general trends observed in other squamates,
      our comparisons indicate major differences in the developmental sequence of
      several tissues, including early craniofacial characters. Detailed analysis of
      both embryonic skull development and adult skull shape, using a comparative
      approach integrating CT-scans and gene expression studies in P. vitticeps as well
      as comparative embryology and 3D geometric morphometrics in a large dataset of
      lizards and snakes, highlights the extreme adult skull shape of P. vitticeps and
      further indicates that heterochrony has played a key role in the early
      development and ossification of squamate skull bones. Such detailed studies of
      embryonic character development, craniofacial patterning, and bone formation are
      essential for the establishment of well-selected squamate species as Evo-Devo
      model organisms. We expect that P. vitticeps will continue to emerge as a new
      attractive model organism for understanding developmental and molecular processes
      underlying tissue formation, morphology, and evolution.

PMID- 29643814
TI  - Impact of Short-Term Training Camp on Aortic Blood Pressure in Collegiate
      Endurance Runners.
AB  - To investigate the influence of short-term vigorous endurance training on aortic
      blood pressure (BP), pulse wave analysis was performed in 36 highly trained elite
      collegiate endurance runners before and after a 7-day intense training camp.
      Subjects participated three training sessions per day, which mainly consisted of
      long distance running and sprint training to reach the daily target distance of
      26 km. After the camp, they were divided into two groups based on whether the
      target training was achieved. Aortic systolic BP, pulse pressure, and tension
      time index (TTI, a surrogate index of the myocardial oxygen demand) were
      significantly elevated after the camp in the accomplished group but not in the
      unaccomplished group, whereas the brachial BP remained unchanged in both groups.
      The average daily training distance was significantly correlated with the changes
      in aortic systolic BP (r = 0.608, p = 0.0002), pulse pressure (r = 0.415, p =
      0.016), and TTI (r = 0.438, p = 0.011). These results suggest that aortic BP is
      affected by a short-term vigorous training camp even in highly trained elite
      endurance athletes presumably due to a greater training volume compared to usual.

PMID- 29643815
TI  - Mechanical Characterization of the Vessel Wall by Data Assimilation of
      Intravascular Ultrasound Studies.
AB  - Atherosclerotic plaque rupture and erosion are the most important mechanisms
      underlying the sudden plaque growth, responsible for acute coronary syndromes and
      even fatal cardiac events. Advances in the understanding of the culprit plaque
      structure and composition are already reported in the literature, however, there
      is still much work to be done toward in-vivo plaque visualization and mechanical
      characterization to assess plaque stability, patient risk, diagnosis and
      treatment prognosis. In this work, a methodology for the mechanical
      characterization of the vessel wall plaque and tissues is proposed based on the
      combination of intravascular ultrasound (IVUS) imaging processing, data
      assimilation and continuum mechanics models within a high performance computing
      (HPC) environment. Initially, the IVUS study is gated to obtain volumes of image
      sequences corresponding to the vessel of interest at different cardiac phases.
      These sequences are registered against the sequence of the end-diastolic phase to
      remove transversal and longitudinal rigid motions prescribed by the moving
      environment due to the heartbeat. Then, optical flow between the image sequences
      is computed to obtain the displacement fields of the vessel (each associated to a
      certain pressure level). The obtained displacement fields are regarded as
      observations within a data assimilation paradigm, which aims to estimate the
      material parameters of the tissues within the vessel wall. Specifically, a
      reduced order unscented Kalman filter is employed, endowed with a forward
      operator which amounts to address the solution of a hyperelastic solid mechanics
      model in the finite strain regime taking into account the axially stretched state
      of the vessel, as well as the effect of internal and external forces acting on
      the arterial wall. Due to the computational burden, a HPC approach is mandatory.
      Hence, the data assimilation and computational solid mechanics computations are
      parallelized at three levels: (i) a Kalman filter level; (ii) a cardiac phase
      level; and (iii) a mesh partitioning level. To illustrate the capabilities of
      this novel methodology toward the in-vivo analysis of patient-specific vessel
      constituents, mechanical material parameters are estimated using in-silico and in
      vivo data retrieved from IVUS studies. Limitations and potentials of this
      approach are exposed and discussed.

PMID- 29643816
TI  - Frequency-Specific Fractal Analysis of Postural Control Accounts for Control
      Strategies.
AB  - Diverse indicators of postural control in Humans have been explored for decades,
      mostly based on the trajectory of the center-of-pressure. Classical approaches
      focus on variability, based on the notion that if a posture is too variable, the
      subject is not stable. Going deeper, an improved understanding of underlying
      physiology has been gained from studying variability in different frequency
      ranges, pointing to specific short-loops (proprioception), and long-loops (visuo
      vestibular) in neural control. More recently, fractal analyses have proliferated
      and become useful additional metrics of postural control. They allowed
      identifying two scaling phenomena, respectively in short and long timescales.
      Here, we show that one of the most widely used methods for fractal analysis,
      Detrended Fluctuation Analysis, could be enhanced to account for scalings on
      specific frequency ranges. By computing and filtering a bank of synthetic fractal
      signals, we established how scaling analysis can be focused on specific frequency
      components. We called the obtained method Frequency-specific Fractal Analysis
      (FsFA) and used it to associate the two scaling phenomena of postural control to
      proprioceptive-based control loop and visuo-vestibular based control loop. After
      that, convincing arguments of method validity came from an application on the
      study of unaltered vs. altered postural control in athletes. Overall, the
      analysis suggests that at least two timescales contribute to postural control: a
      velocity-based control in short timescales relying on proprioceptive sensors, and
      a position-based control in longer timescales with visuo-vestibular sensors,
      which is a brand-new vision of postural control. Frequency-specific scaling
      exponents are promising markers of control strategies in Humans.

PMID- 29643817
TI  - Overexpression of beta-Arrestin1 in the Rostral Ventrolateral Medulla
      Downregulates Angiotensin Receptor and Lowers Blood Pressure in Hypertension.
AB  - Background: Hypertension is characterized by sympathetic overactivity, which is
      associated with an enhancement in angiotensin receptor type I (AT1R) in the
      rostral ventrolateral medulla (RVLM). beta-arrestin1, a canonical scaffold
      protein, has been suggested to show a negative effect on G protein-coupled
      receptors via its internalization and desensitization and/or the biased signaling
      pathway. The major objectives of the present study were to observe the effect of
      beta-arrestin1 overexpression in the RVLM on cardiovascular regulation in
      spontaneously hypertensive rats (SHR), and further determine the effect of beta
      arrestin1 on AT1R expression in the RVLM. Methods: The animal model of beta
      arrestin1 overexpression was induced by bilateral injection of adeno-associated
      virus containing Arrb1 gene (AAV-Arrb1) into the RVLM of WKY and SHR. Results:
      beta-arrestin1 was expressed on the pre-sympathetic neurons in the RVLM, and its
      expression in the RVLM was significantly (P < 0.05) downregulated by an average
      of 64% in SHR than WKY. Overexpression of beta-arrestin1 in SHR significantly
      decreased baseline levels of blood pressure and renal sympathetic nerve activity,
      and attenuated cardiovascular effects induced by RVLM injection of angiotensin II
      (100 pmol). Furthermore, beta-arrestin1 overexpression in the RVLM significantly
      reduced the expression of AT1R by 65% and NF-kappaB p65 phosphorylation by 66% in
      SHR. It was confirmed that beta-arrestin1 overexpression in the RVLM led to an
      enhancement of interaction between beta-arrestin1 and IkappaB-alpha. Conclusion:
      Overexpression of beta-arrestin1 in the RVLM reduces BP and sympathetic outflow
      in hypertension, which may be associated with NFkappaB-mediated AT1R
      downregulation.

PMID- 29643818
TI  - Intrinsic Hormone-Like Molecules and External Root Resorption During Orthodontic
      Tooth Movement. A Systematic Review and Meta-Analysis in Preclinical in-Vivo
      Research.
AB  - Background: External root resorption constitutes an adverse effect of orthodontic
      treatment. The aim of the present meta-analysis was to identify the effect of
      induced intrinsic/ hormone-like molecules such as prostaglandins, interleukins
      and others on external root resorption after orthodontic tooth movement in
      experimental animals Methods: An electronic database search of the literature was
      performed (Medline via PubMed, EMBASE, LILACS, and Open Gray). Search terms
      included root resorption, tooth movement and animal type. Risk of bias assessment
      was made using the SYRCLE guidelines for animal studies and reporting quality was
      assessed through ARRIVE. Random effects meta-analysis was performed for the
      outcome root resorption after orthodontic tooth movement. Results: Of the 124
      articles initially retrieved, 13 were eligible for inclusion in the systematic
      review, while only 2 were included in the quantitative synthesis. Five studies
      investigated the effect of Prostaglandin E2, four studies the effect of
      Thyroxine, two the effect of Calcium ions (Ca++), while the rest investigated
      Misoprostol, Interleukin-12 and Interleukin-4. Risk of Bias in all studies was
      judged to be high overall, while reporting quality was suboptimal. According to
      the quantitative synthesis, there was no difference in root resorption after
      orthodontic tooth movement when Prostaglandin E2 coupled with Ca++ was
      administered in comparison to no substance administration (SMD: 0.48 mm2; 95% CI:
      -0.22, 1.19; p = 0.18). Conclusions: Overall, there was no evidence to suggest a
      variation in root resorption when Prostaglandin E2 and Ca++ were administered,
      while there is an overriding need for further high quality experimental studies
      to inform available evidence on the effect of intrinsic substances on external
      root resorption.

PMID- 29643819
TI  - HMGB1 Increases IL-1beta Production in Vascular Smooth Muscle Cells via NLRP3
      Inflammasome.
AB  - Vascular smooth muscle cells (VSMCs) are the major cell type in the blood vessel
      walls, and their phenotypic modulation is a key cellular event driving vascular
      remodeling. Although high mobility group box-1 (HMGB1) plays a pivotal role in
      inflammatory processes after vascular injuries, the importance of the links
      between VSMCs, HMGB1 and vascular inflammation has not been clarified. To prove
      the hypothesis that VSMCs might be active players in vascular inflammation by
      secreting inflammatory cytokines, we investigated the proinflammatory effects of
      HMGB1 and its intermediary signaling pathways in VSMCs. When cultured human VSMCs
      were stimulated with HMGB1 (10-500 ng/ml), IL-1beta production was markedly
      increased. HMGB1 also increased the expression of NLRP3 inflammasome components
      including NLRP3, ASC and caspase-1. Among these components, HMGB1-induced
      expressions of NLRP3 and caspase-1 were markedly attenuated in TLR2 siRNA
      transfected cells, whereas ASC and caspase-1 expressions were reduced in RAGE
      deficient cells. In TLR4-deficient cells, HMGB1-induced caspase-1 expression was
      significantly attenuated. Moreover, IL-1beta production in HMGB1-stimulated cells
      was significantly reduced in cells transfected with caspase-1 siRNA as well as in
      cells treated with monoclonal antibodies or siRNAs for TLR2, TLR4 and RAGE.
      Overall, this study identified a pivotal role for NLRP3 inflammasome and its
      receptor signaling involved in the production of IL-1beta in VSMCs stimulated
      with HMGB1. Thus, targeting HMGB1 signaling in VSMCs offers a promising
      therapeutic strategy for treating vascular remodeling diseases.

PMID- 29643820
TI  - The Attribution of Mental Health Problems to Jinn: An Explorative Study in a
      Transcultural Psychiatric Outpatient Clinic.
AB  - Background: Among Muslim patients, a common cultural concept of distress is the
      notion that jinn may be the cause of mental health problems, especially in the
      presence of hallucinations. Objective: This study examines the frequency with
      which this attribution style is manifest in a specific psychiatric outpatient
      population with a Muslim background. Methods: Of all patients registered at an
      outpatient clinic specialized in transcultural psychiatry, data were collected on
      folk belief, religion, hallucinations (if present), and medical diagnosis.
      Through a search in the electronic medical files, the notes made during the first
      contact and first psychiatric examination were screened for the keywords "evil
      eye," "magic," "voodoo," and "jinn." In addition, new eligible cases were
      accepted. Results: From all 551 patients thus screened, 118 were eligible for
      participation. Of these, 49 (41.5%) were interviewed using a semi-structured
      questionnaire. Among them, 21 (43%) were positive that their psychiatric symptoms
      were caused by jinn, whereas 13 (27%) thought not, and 15 (31%) were in doubt. No
      less than 87.2% had experienced hallucinations during their lives. Among the
      relatively large proportion of eligible patients who did not participate (58.5%),
      many expressed a fear for stigmatization or metaphysical repercussions if they
      spoke about jinn. Conclusion: The phenomenon of attributing mental health
      symptoms to jinn was much more common in this population of Muslim patients than
      previously assumed. This underscores the need for proper knowledge of Muslim
      explanatory models of disease and for the use of culturally sensitive
      interviewing techniques in this population.

PMID- 29643821
TI  - Influence of an Intermediate Option on the Description-Experience Gap and
      Information Search.
AB  - Research shows that people tend to overweight small probabilities in description
      and underweight them in experience, thereby leading to a different pattern of
      choices between description and experience; a phenomenon known as the Description
      Experience (DE) gap. However, little is known on how the addition of an
      intermediate option and contextual framing influences the DE gap and people's
      search strategies. This paper tests the effects of an intermediate option and
      contextual framing on the DE gap and people's search strategies, where problems
      require search for information before a consequential choice. In the first
      experiment, 120 participants made choice decisions across investment problems
      that differed in the absence or presence of an intermediate option. Results
      showed that adding an intermediate option did not reduce the DE gap on the
      maximizing option across a majority of problems. There were a large majority of
      choices for the intermediate option. Furthermore, there was an increase in
      switching between options due to the presence of the intermediate option. In the
      second experiment, 160 participants made choice decisions in problems like those
      presented in experiment 1; however, problems lacked the investment framing.
      Results replicated findings from the first experiment and showed a similar DE gap
      on the maximizing option in a majority of problems in both the absence and
      presence of the intermediate option. Again, there were a large majority of
      choices for the intermediate option. Also, there was an increase in switching
      between options due to the presence of the intermediate option. Meta-analyses
      revealed that the absence or presence of the intermediate option created certain
      differences in the strength of frequency and recency processes. Also, a single
      natural-mean heuristic model was able to account for the experimental results
      across both experiments. We discuss implications of our findings to consequential
      decisions made after information search.

PMID- 29643822
TI  - Working Memory and Reinforcement Schedule Jointly Determine Reinforcement
      Learning in Children: Potential Implications for Behavioral Parent Training.
AB  - Introduction: Behavioral Parent Training (BPT) is often provided for childhood
      psychiatric disorders. These disorders have been shown to be associated with
      working memory impairments. BPT is based on operant learning principles, yet how
      operant principles shape behavior (through the partial reinforcement (PRF)
      extinction effect, i.e., greater resistance to extinction that is created when
      behavior is reinforced partially rather than continuously) and the potential role
      of working memory therein is scarcely studied in children. This study explored
      the PRF extinction effect and the role of working memory therein using
      experimental tasks in typically developing children. Methods: Ninety-seven
      children (age 6-10) completed a working memory task and an operant learning task,
      in which children acquired a response-sequence rule under either continuous or
      PRF (120 trials), followed by an extinction phase (80 trials). Data of 88
      children were used for analysis. Results: The PRF extinction effect was
      confirmed: We observed slower acquisition and extinction in the PRF condition as
      compared to the continuous reinforcement (CRF) condition. Working memory was
      negatively related to acquisition but not extinction performance. Conclusion:
      Both reinforcement contingencies and working memory relate to acquisition
      performance. Potential implications for BPT are that decreasing working memory
      load may enhance the chance of optimally learning through reinforcement.

PMID- 29643823
TI  - A New Look to a Classic Issue: Reasoning and Academic Achievement at Secondary
      School.
AB  - Higher-order thinking abilities such as abstract reasoning and meaningful school
      learning occur sequentially. The fulfillment of these tasks demands that people
      activate and use all of their working memory resources in a controlled and
      supervised way. The aims of this work were: (a) to study the interplay between
      two new reasoning measures, one mathematical (Cognitive Reflection Test) and the
      other verbal (Deductive Reasoning Test), and a third classical visuo-spatial
      reasoning measure (Raven Progressive Matrices Test); and (b) to investigate the
      relationship between these measures and academic achievement. Fifty-one 4th grade
      secondary school students participated in the experiment and completed the three
      reasoning tests. Academic achievement measures were the final numerical scores in
      seven basic subjects. The results demonstrated that cognitive reflection, visual,
      and verbal reasoning are intimately related and predicts academic achievement.
      This work confirms that abstract reasoning constitutes the most important higher
      order cognitive ability that underlies academic achievement. It also reveals the
      importance of dual processes, verbal deduction and metacognition in ordinary
      teaching and learning at school.

PMID- 29643824
TI  - The Topological Properties of Stimuli Influence Fear Generalization and
      Extinction in Humans.
AB  - Fear generalization is an etiologically significant indicator of anxiety
      disorders, and understanding how to inhibit it is important in their treatment.
      Prior studies have found that reducing fear generalization using a generalization
      stimulus (GS) is ineffective in removing a conditioned fear that incorporates
      local features, and that topological properties appear to play a comparatively
      more significant role in the processes of perception and categorization. Our
      study utilized a conditioned-fear generalization design to examine whether the
      topological properties of stimuli influence the generalization and return of
      fear. Fear was indexed using online expectancy ratings and skin conductance
      responses (SCRs). The study's 52 participants were divided into three groups:
      Group 1, conditioned danger cue (CS+) extinction; Group 2, extinction of one GS;
      Group 3, extinction of three GSs. We found that the three groups acquired
      conditioned fear at the same level. In the generalization and extinction phase,
      fear was transferred to the GS with the same topological properties as CS+, and
      gradual decreases in both shock expectancy and SCRs over non-reinforced
      extinction trials were observed. In the test phase, participants' online
      expectancy ratings indicated that fear did not return in Group 1, but did return
      in Groups 2 and 3. All three groups demonstrated successful GS fear extinction,
      but only Group 1 did not show a return of fear for CS+. Regarding SCRs results,
      none of the groups demonstrated a return of fear, suggesting that utilization of
      topological properties successfully reduced the return of conditioned fear. Our
      results indicate that, in clinical settings, using GS with topological
      equivalence to CS+ might offer a potential method with which to extinct
      conditioned fear.

PMID- 29643825
TI  - Factors Influencing Right Hemisphere Engagement During Metaphor Comprehension.
AB  - Although the left hemisphere is critical for language, clinical, behavioral, and
      neuroimaging research suggest that the right hemisphere also contributes to
      language comprehension. In particular, research has suggested that figurative
      language may be one type of language that preferentially engages right hemisphere
      regions. However, there is disagreement about whether these regions within the
      right hemisphere are sensitive to figurative language per se or to other factors
      that co-vary with figurativeness. In this article, we will review the
      neuroimaging literature on figurative language processing, focusing on metaphors,
      within the context of several theoretical perspectives that have been proposed
      about hemispheric function in language. Then we will examine three factors that
      may influence right hemisphere engagement: novelty, task difficulty, and context.
      We propose that factors that increase integration demands drive right hemisphere
      involvement in language processing, and that such recruitment is not limited to
      figurative language.

PMID- 29643826
TI  - A Neurodynamic Model of Feature-Based Spatial Selection.
AB  - Huang and Pashler (2007) suggested that feature-based attention creates a special
      form of spatial representation, which is termed a Boolean map. It partitions the
      visual scene into two distinct and complementary regions: selected and not
      selected. Here, we developed a model of a recurrent competitive network that is
      capable of state-dependent computation. It selects multiple winning locations
      based on a joint top-down cue. We augmented a model of the WTA circuit that is
      based on linear-threshold units with two computational elements: dendritic non
      linearity that acts on the excitatory units and activity-dependent modulation of
      synaptic transmission between excitatory and inhibitory units. Computer
      simulations showed that the proposed model could create a Boolean map in response
      to a featured cue and elaborate it using the logical operations of intersection
      and union. In addition, it was shown that in the absence of top-down guidance,
      the model is sensitive to bottom-up cues such as saliency and abrupt visual
      onset.

PMID- 29643827
TI  - Do Future Limitation Perspective in Cancer Patients Predict Fear of Cancer
      Recurrence, Mental Distress, and the Ventromedial Prefrontal Cortex Activity?
AB  - Life-threatening diseases (e.g., cancer) affect people's future time perspective
      (FTP) and affect their mental health. When one's lifetime is perceived as running
      out, the individual possesses a future limitation perspective (FLP), which is one
      of factors in FTP. In this study, we explored the structural relationship between
      FLP, fear of cancer recurrence (FCR), mental health status (MHS), and brain
      activity in patients with cancer. Cancer patients were divided into two groups
      using the FTP scale and Feelings About Life Scale: a strong FLP group (S-FLP) and
      a weak FLP group (W-FLP). For these groups, we measured cancer patients' MHS
      using the Symptom Checklist (SCL-90) and FCR using the Cancer Acceptance Scale;
      brain activity was measured using resting-state functional magnetic resonance
      imaging (rs-fMRI). Behavioral results showed that the S-FLP group had higher
      mental symptoms and FCR scores than did the W-FLP group. Neuroimaging results
      revealed that spontaneous brain activity in the ventromedial prefrontal cortex
      (vmPFC) was stronger in the W-FLP group than in the S-FLP group. Moreover, brain
      activity in the vmPFC negatively correlated with FLP, FCR, and SCL-90 scores only
      in the S-FLP group, and the model constructed further indicated that FCR and SCL
      90 scores fully mediated the relationship between FLP and vmPFC activities. These
      findings suggested that a strong FLP might lead to mental disorders and greater
      FCR, which might change the spontaneous activity of the vmPFC in cancer patients.

PMID- 29643828
TI  - Lateralization of Sucrose Responsiveness and Non-associative Learning in
      Honeybees.
AB  - Lateralization is a fundamental property of the human brain that affects
      perceptual, motor, and cognitive processes. It is now acknowledged that left
      right laterality is widespread across vertebrates and even some invertebrates
      such as fruit flies and bees. Honeybees, which learn to associate an odorant (the
      conditioned stimulus, CS) with sucrose solution (the unconditioned stimulus, US),
      recall this association better when trained using their right antenna than they
      do when using their left antenna. Correspondingly, olfactory sensilla are more
      abundant on the right antenna and odor encoding by projection neurons of the
      right antennal lobe results in better odor differentiation than those of the left
      one. Thus, lateralization arises from asymmetries both in the peripheral and
      central olfactory system, responsible for detecting the CS. Here, we focused on
      the US component and studied if lateralization exists in the gustatory system of
      Apis mellifera. We investigated whether sucrose sensitivity is lateralized both
      at the level of the antennae and the fore-tarsi in two independent groups of
      bees. Sucrose sensitivity was assessed by presenting bees with a series of
      increasing concentrations of sucrose solution delivered either to the left or the
      right antenna/tarsus and measuring the proboscis extension response to these
      stimuli. Bees experienced two series of stimulations, one on the left and the
      other on the right antenna/tarsus. We found that tarsal responsiveness was
      similar on both sides and that the order of testing affects sucrose
      responsiveness. On the contrary, antennal responsiveness to sucrose was higher on
      the right than on the left side, and this effect was independent of the order of
      antennal stimulation. Given this asymmetry, we also investigated antennal
      lateralization of habituation to sucrose. We found that the right antenna was
      more resistant to habituation, which is consistent with its higher sucrose
      sensitivity. Our results reveal that the gustatory system presents a peripheral
      lateralization that affects stimulus detection and non-associative learning.
      Contrary to the olfactory system, which is organized in two distinct brain
      hemispheres, gustatory receptor neurons converge into a single central region
      termed the subesophagic zone (SEZ). Whether the SEZ presents lateralized
      gustatory processing remains to be determined.

PMID- 29643829
TI  - If Neuroscience Needs Behavior, What Does Psychology Need?

PMID- 29643830
TI  - Accuracy and Feasibility of an Android-Based Digital Assessment Tool for Post
      Stroke Visual Disorders-The StrokeVision App.
AB  - Background: Visual impairment affects up to 70% of stroke survivors. We designed
      an app (StrokeVision) to facilitate screening for common post stroke visual
      issues (acuity, visual fields, and visual inattention). We sought to describe the
      test time, feasibility, acceptability, and accuracy of our app-based digital
      visual assessments against (a) current methods used for bedside screening and (b)
      gold standard measures. Methods: Patients were prospectively recruited from acute
      stroke settings. Index tests were app-based assessments of fields and inattention
      performed by a trained researcher. We compared against usual clinical screening
      practice of visual fields to confrontation, including inattention assessment
      (simultaneous stimuli). We also compared app to gold standard assessments of
      formal kinetic perimetry (Goldman or Octopus Visual Field Assessment); and pencil
      and paper-based tests of inattention (Albert's, Star Cancelation, and Line
      Bisection). Results of inattention and field tests were adjudicated by a
      specialist Neuro-ophthalmologist. All assessors were masked to each other's
      results. Participants and assessors graded acceptability using a bespoke scale
      that ranged from 0 (completely unacceptable) to 10 (perfect acceptability).
      Results: Of 48 stroke survivors recruited, the complete battery of index and
      reference tests for fields was successfully completed in 45. Similar
      acceptability scores were observed for app-based [assessor median score 10 (IQR:
      9-10); patient 9 (IQR: 8-10)] and traditional bedside testing [assessor 10 (IQR:
      9-10); patient 10 (IQR: 9-10)]. Median test time was longer for app-based testing
      [combined time to completion of all digital tests 420 s (IQR: 390-588)] when
      compared with conventional bedside testing [70 s, (IQR: 40-70)], but shorter than
      gold standard testing [1,260 s, (IQR: 1005-1,620)]. Compared with gold standard
      assessments, usual screening practice demonstrated 79% sensitivity and 82%
      specificity for detection of a stroke-related field defect. This compares with
      79% sensitivity and 88% specificity for StrokeVision digital assessment.
      Conclusion: StrokeVision shows promise as a screening tool for visual
      complications in the acute phase of stroke. The app is at least as good as usual
      screening and offers other functionality that may make it attractive for use in
      acute stroke. Clinical Trial Registration:
      https://ClinicalTrials.gov/ct2/show/NCT02539381.

PMID- 29643832
TI  - Corrigendum: Matrix Metalloproteinases and Blood-Brain Barrier Disruption in
      Acute Ischemic Stroke.
AB  - [This corrects the article on p. 32 in vol. 4, PMID: 23565108.].

PMID- 29643831
TI  - Altered Intracortical Inhibition in Chronic Traumatic Diffuse Axonal Injury.
AB  - Background: Overactivation of NMDA-mediated excitatory processes and excess of
      GABA-mediated inhibition are attributed to the acute and subacute phases,
      respectively, after a traumatic brain injury (TBI). However, there are few
      studies regarding the circuitry during the chronic phase of brain injury.
      Objective: To evaluate the cortical excitability (CE) during the chronic phase of
      TBI in victims diagnosed with diffuse axonal injury (DAI). Methods: The 22 adult
      subjects were evaluated after a minimum of 1 year from the onset of moderate or
      severe TBI. Each of the subjects first had a comprehensive neuropsychological
      assessment to evaluate executive functions-attention, memory, verbal fluency, and
      information processing speed. Then, CE assessment was performed with a circular
      coil applying single-pulse and paired-pulse transcranial magnetic stimulation
      over the cortical representation of the abductor pollicis brevis muscle on M1 of
      both hemispheres. The CE parameters measured were resting motor threshold (RMT),
      motor-evoked potentials (MEPs), short-interval intracortical inhibition (SIICI),
      and intracortical facilitation (ICF). All data were compared with that of a
      control group that consisted of the healthy age-matched individuals. Results: No
      significant differences between the left and right hemispheres were detected in
      the DAI subjects. Therefore, parameters were analyzed as pooled data. Values of
      RMT, MEPs, and ICF from DAI patients were within normal limits. However, SIICI
      values were higher in the DAI group-DAI SIICI = 1.28 (1.01; 1.87) versus the
      control value = 0.56 (0.33; 0.69)-suggesting that they had a disarranged
      inhibitory system (p < 0.001). By contrast, the neuropsychological findings had
      weak correlation with the CE data. Conclusion: As inhibition processes involve
      GABA-mediated circuitry, it is likely that the DAI pathophysiology itself
      (disruption of axons) may deplete GABA and contribute to ongoing disinhibition of
      these neural circuits of the cerebrum during the chronic phase of DAI.

PMID- 29643833
TI  - In Vivo Confocal Microscopic Evaluation of Corneal Nerve Fibers and Dendritic
      Cells in Patients With Behcet's Disease.
AB  - Central and peripheral nervous system involvement may occur during the course of
      Behcet's disease (BD). In vivo corneal confocal microscopy (CCM) can detect
      corneal small fiber damage and immune cell density. The aim of this study was to
      assess central corneal sensitivity, corneal subepithelial nerve plexus morphology
      and dendritic cell (DC) density in patients with BD. Forty-nine consecutive
      patients with BD and 30 healthy control subjects were included in this cross
      sectional study conducted at a tertiary referral university hospital. Central
      corneal sensitivity was measured using the contact corneal esthesiometer (Cochet
      Bonnet; Luneau, France). The laser scanning CCM (Heidelberg, Germany) was used to
      quantify corneal nerve fiber density (NFD), nerve branch density (NBD), nerve
      fiber length (NFL), and DC density. There was a significant reduction in NFD (P =
      0.001) and NFL (P = 0.031) and an increase in DC density (P = 0.038) in patients
      with BD compared to healthy controls, whereas corneal sensitivity (P = 0.066) and
      NBD (P = 0.067) did not differ significantly. There was no difference in corneal
      sensitivity, corneal nerve parameters, or DC density between BD patients with [n
      = 18 (36.7%)] and without a previous history of uveitis (P > 0.05 for all).
      Disease duration [median (IQR), 6.5 (4.0-14.5) years] correlated with corneal
      sensitivity (rho = -0.463; P = 0.001) and NFD (rho = -0.304; P = 0.034) and
      corneal sensitivity correlated with NFD (rho = 0.411; P = 0.003) and NFL (rho =
      0.295; P = 0.039) in patients with BD. CCM demonstrates corneal sub-basal nerve
      fiber loss and increased DC density, providing a non-invasive ophthalmic means to
      identify peripheral neuropathy and inflammation in patients with BD.

PMID- 29643835
TI  - Identification of Neuroendocrine Stress Response-Related Circulating MicroRNAs as
      Biomarkers for Type 2 Diabetes Mellitus and Insulin Resistance.
AB  - Background: Chronic stress plays an important role in the development of type 2
      diabetes mellitus (T2DM) and insulin resistance (IR). MicroRNAs (miRNAs) play key
      roles in mediating stress responses by regulating the expression of target genes.
      This study systematically screened and identified the neuroendocrine stress
      response-related circulating miRNAs which are associated with T2DM and IR.
      Methods: Based on the differential plasma expression profiles between individuals
      with and without T2DM, stress-related miRNAs were selected from those differently
      expressed miRNAs whose targets are involved in known neuroendocrine pathway of
      stress response. Candidate miRNAs were further validated by quantitative real
      time polymerase chain reaction in a large sample, including 112 T2DM patients, 72
      individuals with impaired fasting glucose (IFG), and 94 healthy controls. The
      association between miRNA expression and potential risk of T2DM and IFG was
      assessed by multivariate logistic regression models. The miRNA predictors of IR
      were identified by stepwise multiple regression analysis. The diagnostic
      performance for T2DM was evaluated by area under the curve (AUC) of receiver
      operating characteristic (ROC). Results: let-7b, let-7i, miR-142, miR-144, miR
      155, and miR-29a were selected as candidate miRNAs for validation. Increased
      expression of let-7b, miR-144, and miR-29a and decreased expression of miR-142
      were significant independent predictors of T2DM, IFG, and IR (P < 0.0125). These
      miRNAs significantly correlated with stress hormone levels (P < 0.0125). A three
      miRNA panel, including let-7b, miR-142, and miR-144 had a high accuracy for
      diagnosing T2DM (AUC = 0.871, 95% CI: 0.822-0.919). Conclusion: let-7b, miR-142,
      miR-144, and miR-29a in plasma may be important markers of neuroendocrine stress
      response and may play a role in the pathogenesis of T2DM and IR.

PMID- 29643836
TI  - Tau Phosphorylation in Female Neurodegeneration: Role of Estrogens, Progesterone,
      and Prolactin.
AB  - Sex differences are important to consider when studying different psychiatric,
      neurodevelopmental, and neurodegenerative disorders, including Alzheimer's
      disease (AD). These disorders can be affected by dimorphic changes in the central
      nervous system and be influenced by sex-specific hormones and neuroactive
      steroids. In fact, AD is more prevalent in women than in men. One of the main
      characteristics of AD is the formation of neurofibrillary tangles, composed of
      the phosphoprotein Tau, and neuronal loss in specific brain regions. The scope of
      this work is to review the existing evidence on how a set of hormones (estrogen,
      progesterone, and prolactin) affect tau phosphorylation in the brain of females
      under both physiological and pathological conditions.

PMID- 29643834
TI  - Metabolic Impact on the Hypothalamic Kisspeptin-Kiss1r Signaling Pathway.
AB  - A large body of data has established the hypothalamic kisspeptin (KP) and its
      receptor, KISS1R, as major players in the activation of the neuroendocrine
      reproductive axis at the time of puberty and maintenance of reproductive capacity
      in the adult. Due to its strategic location, this ligand-receptor pair acts as an
      integrator of cues from gonadal steroids as well as of circadian and seasonal
      variation-related information on the reproductive axis. Besides these cues, the
      activity of the hypothalamic KP signaling is very sensitive to the current
      metabolic status of the body. In conditions of energy imbalance, either positive
      or negative, a number of alterations in the hypothalamic KP signaling pathway
      have been documented in different mammalian models including nonhuman primates
      and human. Deficiency of metabolic fuels during fasting causes a marked reduction
      of Kiss1 gene transcript levels in the hypothalamus and, hence, decreases the
      output of KP-containing neurons. Food intake or exogenous supply of metabolic
      cues, such as leptin, reverses metabolic insufficiency-related changes in the
      hypothalamic KP signaling. Likewise, alterations in Kiss1 expression have also
      been reported in other situations of energy imbalance like diabetes and obesity.
      Information related to the body's current metabolic status reaches to KP neurons
      both directly as well as indirectly via a complex network of other neurons. In
      this review article, we have provided an updated summary of the available
      literature on the regulation of the hypothalamic KP-Kiss1r signaling by metabolic
      cues. In particular, the potential mechanisms of metabolic impact on the
      hypothalamic KP-Kiss1r signaling, in light of available evidence, are discussed.

PMID- 29643837
TI  - Insulin-Like Growth Factor Binding Proteins and IGFBP Proteases: A Dynamic System
      Regulating the Ovarian Folliculogenesis.
AB  - The aim of the present article is to update our understanding of the expression
      of the insulin-like growth factor binding proteins (IGFBPs), IGFBP proteases and
      their implication in the different processes of ovarian folliculogenesis in
      mammals. In the studied species, IGFs and several small-molecular weight IGFBPs
      (in particular IGFBP-2 and IGFBP-4) are considered, respectively, as stimulators
      and inhibitors of follicular growth and maturation. IGFs play a key role in
      sensitizing ovarian granulosa cells to FSH action during terminal follicular
      growth. Concentrations of IGFBP-2 and IGFBP-4 in follicular fluid strongly
      decrease during follicular growth, leading to an increase in IGF bioavailability.
      Inversely, atresia is characterized by an increase of IGFBP-2 and IGFBP-4 levels,
      leading to a decrease in IGF bioavailability. Changes in intrafollicular IGFBPs
      content are due to variations in mRNA expression and/or proteolytic degradation
      by the pregnancy-associated plasma protein-A (PAPP-A), and likely participates in
      the selection of dominant follicles. The identification of PAPP-A2, as an IGFBP-3
      and -5 protease, and stanniocalcins (STCs) as inhibitors of PAPP-A activity
      extends the IGF system. Studies on their implication in folliculogenesis in
      mammals are still in the early stages.

PMID- 29643838
TI  - Identification of Transmembrane Protease Serine 2 and Forkhead Box A1 As the
      Potential Bisphenol A Responsive Genes in the Neonatal Male Rat Brain.
AB  - Perinatal exposure of Bisphenol A (BPA) to rodents modifies their behavior in
      later life. To understand how BPA modifies their neurodevelopmental process, we
      first searched for BPA responsive genes from androgen and estrogen receptor
      signaling target genes by polymerase chain reaction array in the neonatal male
      rat brain. We used a transgenic strain of Wistar rats carrying enhanced green
      fluorescent protein tagged to gonadotropin-inhibitory hormone (GnIH) promoter to
      investigate the possible interaction of BPA responsive genes and GnIH neurons. We
      found upregulation of transmembrane protease serine 2 (Tmprss2), an androgen
      receptor signaling target gene, and downregulation of Forkhead box A1 (Foxa1), an
      ER signaling target gene, in the medial amygdala of male rats that were
      subcutaneously administered with BPA from day 1 to 3. Tmprss2-immunoreactive (ir)
      cells were distributed in the olfactory bulb, cerebral cortex, hippocampus,
      amygdala, and hypothalamus in 3 days old but not in 1-month-old male rats.
      Density of Tmprss2-ir cells in the medial amygdala was increased by daily
      administration of BPA from day 1 to 3. Tmprss2 immunoreactivity was observed in
      26.5% of GnIH neurons clustered from the ventral region of the ventromedial
      hypothalamic nucleus to the dorsal region of the arcuate nucleus of 3-day-old
      male rat hypothalamus. However, Tmprss2 mRNA expression significantly decreased
      in the amygdala and hypothalamus of 1-month-old male rats. Foxa1 mRNA expression
      was higher in the hypothalamus than the amygdala in 3 days old male rats. Intense
      Foxa1-ir cells were only found in the peduncular part of lateral hypothalamus of
      3-day-old male rats. Density of Foxa1-ir cells in the hypothalamus was decreased
      by daily administration of BPA from day 1 to 3. Foxa1 mRNA expression in the
      hypothalamus also significantly decreased at 1 month. These results suggest that
      BPA disturbs the neurodevelopmental process and behavior of rats later in their
      life by modifying Tmprss2 and Foxa1 expressions in the brain.

PMID- 29643839
TI  - Variance Component Selection With Applications to Microbiome Taxonomic Data.
AB  - High-throughput sequencing technology has enabled population-based studies of the
      role of the human microbiome in disease etiology and exposure response.
      Microbiome data are summarized as counts or composition of the bacterial taxa at
      different taxonomic levels. An important problem is to identify the bacterial
      taxa that are associated with a response. One method is to test the association
      of specific taxon with phenotypes in a linear mixed effect model, which
      incorporates phylogenetic information among bacterial communities. Another type
      of approaches consider all taxa in a joint model and achieves selection via
      penalization method, which ignores phylogenetic information. In this paper, we
      consider regression analysis by treating bacterial taxa at different level as
      multiple random effects. For each taxon, a kernel matrix is calculated based on
      distance measures in the phylogenetic tree and acts as one variance component in
      the joint model. Then taxonomic selection is achieved by the lasso (least
      absolute shrinkage and selection operator) penalty on variance components. Our
      method integrates biological information into the variable selection problem and
      greatly improves selection accuracies. Simulation studies demonstrate the
      superiority of our methods versus existing methods, for example, group-lasso.
      Finally, we apply our method to a longitudinal microbiome study of Human
      Immunodeficiency Virus (HIV) infected patients. We implement our method using the
      high performance computing language Julia. Software and detailed documentation
      are freely available at https://github.com/JingZhai63/VCselection.

PMID- 29643840
TI  - Azole-Resistance in Aspergillus terreus and Related Species: An Emerging Problem
      or a Rare Phenomenon?
AB  - Objectives: Invasive mold infections associated with Aspergillus species are a
      significant cause of mortality in immunocompromised patients. The most frequently
      occurring aetiological pathogens are members of the Aspergillus section Fumigati
      followed by members of the section Terrei. The frequency of Aspergillus terreus
      and related (cryptic) species in clinical specimens, as well as the percentage of
      azole-resistant strains remains to be studied. Methods: A global set (n = 498) of
      A. terreus and phenotypically related isolates was molecularly identified (beta
      tubulin), tested for antifungal susceptibility against posaconazole,
      voriconazole, and itraconazole, and resistant phenotypes were correlated with
      point mutations in the cyp51A gene. Results: The majority of isolates was
      identified as A. terreus (86.8%), followed by A. citrinoterreus (8.4%), A. hortai
      (2.6%), A. alabamensis (1.6%), A. neoafricanus (0.2%), and A. floccosus (0.2%).
      One isolate failed to match a known Aspergillus sp., but was found most closely
      related to A. alabamensis. According to EUCAST clinical breakpoints azole
      resistance was detected in 5.4% of all tested isolates, 6.2% of A. terreus sensu
      stricto (s.s.) were posaconazole-resistant. Posaconazole resistance differed
      geographically and ranged from 0% in the Czech Republic, Greece, and Turkey to
      13.7% in Germany. In contrast, azole resistance among cryptic species was rare 2
      out of 66 isolates and was observed only in one A. citrinoterreus and one A.
      alabamensis isolate. The most affected amino acid position of the Cyp51A gene
      correlating with the posaconazole resistant phenotype was M217, which was found
      in the variation M217T and M217V. Conclusions:Aspergillus terreus was most
      prevalent, followed by A. citrinoterreus. Posaconazole was the most potent drug
      against A. terreus, but 5.4% of A. terreus sensu stricto showed resistance
      against this azole. In Austria, Germany, and the United Kingdom posaconazole
      resistance in all A. terreus isolates was higher than 10%, resistance against
      voriconazole was rare and absent for itraconazole.

PMID- 29643842
TI  - Inhibitory Effects of Sulfate and Nitrate Reduction on Reductive Dechlorination
      of PCP in a Flooded Paddy Soil.
AB  - Pentachlorophenol (PCP) is highly toxic and persistent in soils. Bioreduction of
      PCP often co-occurs with varying concentrations of sulfate and nitrate in flooded
      paddy soils where each can act as an electron acceptor. Anaerobic soil microcosms
      were constructed to evaluate the influence of sulfate and nitrate amendments and
      their redox processes. Microcosms with varying sulfate and nitrate concentrations
      demonstrated an inhibitory effect on reductive dechlorination of PCP compared to
      an untreated control. Compared to nitrate, sulfate exhibited a more significant
      impact on PCP dechlorination, as evidenced by a lower maximum reaction rate and a
      longer time to reach the maximum reaction rate. Dechlorination of PCP was
      initiated at the ortho-position, and then at the para- and meta-positions to form
      3-CP as the final product in all microcosms. Deep sequencing of microbial
      communities in the microcosms revealed a strong variation in bacterial taxon
      among treatments. Specialized microbial groups, such as the genus of
      Desulfovibrio responding to the addition of sulfate, had a potential to mediate
      the competitive microbial dechlorination of PCP. Our results provide an insight
      into the competitive microbial-mediated reductive dechlorination of PCP in
      natural flooded soil or sediment environments.

PMID- 29643843
TI  - SIPSim: A Modeling Toolkit to Predict Accuracy and Aid Design of DNA-SIP
      Experiments.
AB  - DNA Stable isotope probing (DNA-SIP) is a powerful method that links identity to
      function within microbial communities. The combination of DNA-SIP with
      multiplexed high throughput DNA sequencing enables simultaneous mapping of in
      situ assimilation dynamics for thousands of microbial taxonomic units. Hence,
      high throughput sequencing enabled SIP has enormous potential to reveal patterns
      of carbon and nitrogen exchange within microbial food webs. There are several
      different methods for analyzing DNA-SIP data and despite the power of SIP
      experiments, it remains difficult to comprehensively evaluate method accuracy
      across a wide range of experimental parameters. We have developed a toolset
      (SIPSim) that simulates DNA-SIP data, and we use this toolset to systematically
      evaluate different methods for analyzing DNA-SIP data. Specifically, we employ
      SIPSim to evaluate the effects that key experimental parameters (e.g., level of
      isotopic enrichment, number of labeled taxa, relative abundance of labeled taxa,
      community richness, community evenness, and beta-diversity) have on the
      specificity, sensitivity, and balanced accuracy (defined as the product of
      specificity and sensitivity) of DNA-SIP analyses. Furthermore, SIPSim can predict
      analytical accuracy and power as a function of experimental design and community
      characteristics, and thus should be of great use in the design and interpretation
      of DNA-SIP experiments.

PMID- 29643841
TI  - Mouse Models That Enhanced Our Understanding of Adult T Cell Leukemia.
AB  - Adult T cell Leukemia (ATL) is an aggressive lymphoproliferative malignancy
      secondary to infection by the human T-cell leukemia virus type I (HTLV-I) and is
      associated with a dismal prognosis. ATL leukemogenesis remains enigmatic. In the
      era of precision medicine in oncology, mouse models offer one of the most
      efficient in vivo tools for the understanding of the disease biology and
      developing novel targeted therapies. This review provides an up-to-date and
      comprehensive account of mouse models developed in the context of ATL and HTLV-I
      infection. Murine ATL models include transgenic animals for the viral proteins
      Tax and HBZ, knock-outs for key cellular regulators, xenografts and humanized
      immune-deficient mice. The first two groups provide a key understanding of the
      role of viral and host genes in the development of ATL, as well as their
      relationship with the immunopathogenic processes. The third group represents a
      valuable platform to test new targeted therapies against ATL.

PMID- 29643844
TI  - Emerging Roles of N6-Methyladenosine on HIV-1 RNA Metabolism and Viral
      Replication.
AB  - N6-methyladenosine (m6A) is the most abundant internal modification present in
      Eukaryotic mRNA. The functions of this chemical modification are mediated by m6A
      binding proteins (m6A readers) and regulated by methyltransferases (m6A writers)
      and demethylases (m6A erasers), which together are proposed to be responsible of
      a new layer of post-transcriptional control of gene expression. Despite the
      presence of m6A in a retroviral genome was reported more than 40 years ago, the
      recent development of sequencing-based technologies allowing the mapping of m6A
      in a transcriptome-wide manner made it possible to identify the topology and
      dynamics of m6A during replication of HIV-1 as well as other viruses. As such,
      three independent groups recently reported the presence of m6A along the HIV-1
      genomic RNA (gRNA) and described the impact of cellular m6A writers, erasers and
      readers on different steps of viral RNA metabolism and replication.
      Interestingly, while two groups reported a positive role of m6A at different
      steps of viral gene expression it was also proposed that the presence of m6A
      within the gRNA reduces viral infectivity by inducing the early degradation of
      the incoming viral genome. This review summarizes the recent advances in this
      emerging field and discusses the relevance of m6A during HIV-1 replication.

PMID- 29643845
TI  - Spatiotemporal Distribution and Assemblages of Planktonic Fungi in the Coastal
      Waters of the Bohai Sea.
AB  - Fungi play a critical role in the nutrient cycling and ecological function in
      terrestrial and freshwater ecosystems. Yet, many ecological aspects of their
      counterparts in coastal ecosystems remain largely elusive. Using high-throughput
      sequencing, quantitative PCR, and environmental data analyses, we studied the
      spatiotemporal changes in the abundance and diversity of planktonic fungi and
      their abiotic and biotic interactions in the coastal waters of three transects
      along the Bohai Sea. A total of 4362 ITS OTUs were identified and more than 60%
      of which were unclassified Fungi. Of the classified OTUs three major fungal
      phyla, Ascomycota, Basidiomycota, and Chytridiomycota were predominant with
      episodic low dominance phyla Cryptomycota and Mucoromycota (Mortierellales). The
      estimated average Fungi-specific 18S rRNA gene qPCR abundances varied within 4.28
      * 106 and 1.13 * 107copies/L with significantly (P < 0.05) different abundances
      among the transects suggesting potential influence of the different riverine
      inputs. The spatiotemporal changes in the OTU abundance of Ascomycota and
      Basidiomycota phyla coincided significantly (P < 0.05) with nutrients traced to
      riverine inputs and phytoplankton detritus. Among the eight major fungal orders,
      the abundance of Hypocreales varied significantly (P < 0.01) across months while
      Capnodiales, Pleosporales, Eurotiales, and Sporidiobolales varied significantly
      (P < 0.05) across transects. In addition, our results likely suggest a tripartite
      interaction model for the association within members of Cryptomycota
      (hyperparasites), Chytridiomycota (both parasites and saprotrophs), and
      phytoplankton in the coastal waters. The fungal network featured several hubs and
      keystone OTUs besides the display of cooperative and competitive relationship
      within OTUs. These results support the notion that planktonic fungi, hitherto
      mostly undescribed, play diverse ecological roles in marine habitats and further
      outline niche processes, tripartite and co-occurrence interaction as the major
      drivers of their community structure and spatiotemporal distribution in the
      coastal water column.

PMID- 29643846
TI  - LILRB4 Decrease on uDCs Exacerbate Abnormal Pregnancy Outcomes Following
      Toxoplasma gondii Infection.
AB  - Toxoplasma gondii (T. gondii) infection in early pregnancy can result in
      miscarriage, dead fetus, and other abnormalities. The LILRB4 is a central
      inhibitory receptor in uterine dendritic cells (uDCs) that plays essential immune
      regulatory roles at the maternal-fetal interface. In this study, T. gondii
      infected human primary uDCs and T. gondii-infected LILRB4-/- pregnant mice were
      utilized. The immune mechanisms underlying the role of LILRB4 on uDCs were
      explored in the development of abnormal pregnancy outcomes following T. gondii
      infection in vitro and in vivo. Our results showed that the expression levels of
      LILRB4 on uDCs from normal pregnant mice were obviously higher than non-pregnant
      mice, and peaked in mid-gestation. The LILRB4 expression on uDC subsets,
      especially tolerogenic subsets, from mid-gestation was obviously down-regulated
      after T. gondii infection and LILRB4 decrease could further regulate the
      expression of functional molecules (CD80, CD86, and HLA-DR or MHC II) on uDCs,
      contributing to abnormal pregnancy outcomes. Our results will shed light on the
      molecular immune mechanisms of uDCs in abnormal pregnancy outcomes by T. gondii
      infection.

PMID- 29643847
TI  - The Advanced Anaerobic Expanded Granular Sludge Bed (AnaEG) Possessed Temporally
      and Spatially Stable Treatment Performance and Microbial Community in Treating
      Starch Processing Wastewater.
AB  - This study implements temporal and spatial appraisals on the operational
      performance and corresponding microbial community structure of a full-scale
      advanced anaerobic expanded granular sludge bed (AnaEG) which was used to treat
      low organic loading starch processing wastewater. Results showed stable treatment
      efficiency could be maintained with long-term erratic influent quality, and a
      major reaction zone located at the bottom of the AnaEG, where the main pollutant
      removal rate was greater than 90%. Remarkably, high-throughput sequencing of 16S
      rRNA gene amplicons displayed that the predominant members constructed the major
      part of the overall microbial community and showed highly temporal stability.
      They were affiliated to Chloroflexi (16.4%), Proteobacteria (14.01%), Firmicutes
      (8.76%), Bacteroidetes (7.85%), Cloacimonetes (3.21%), Ignavibacteriae (1.80%),
      Synergistetes (1.11%), Thermotogae (0.98%), and Euryarchaeota (3.18%). This part
      of microorganism implemented the long-term stable treatment efficiency of the
      reactor. Simultaneously, an extraordinary spatial homogeneity in the granule
      physic properties and microbial community structure along the vertical direction
      was observed within the AnaEG. In conclusion, the microbial community structure
      and the bioreactor's performance showed notable spatial and temporal consistency,
      and the predominant populations guaranteed a long-term favorable treatment
      performance of the AnaEG. It provides us with a better understanding of the
      mechanism of this recently proposed anaerobic reactor which was used in low
      organic loading wastewater treatment.

PMID- 29643848
TI  - In Vitro and in Vivo Selection of Potentially Probiotic Lactobacilli From
      Nocellara del Belice Table Olives.
AB  - Table olives are increasingly recognized as a vehicle as well as a source of
      probiotic bacteria, especially those fermented with traditional procedures based
      on the activity of indigenous microbial consortia, originating from local
      environments. In the present study, we report characterization at the species
      level of 49 Lactic Acid Bacteria (LAB) strains deriving from Nocellara del Belice
      table olives fermented with the Spanish or Castelvetrano methods, recently
      isolated in our previous work. Ribosomal 16S DNA analysis allowed identification
      of 4 Enterococcus gallinarum, 3 E. casseliflavus, 14 Leuconostoc mesenteroides,
      19 Lactobacillus pentosus, 7 L. coryniformis, and 2 L. oligofermentans. The L.
      pentosus and L. coryniformis strains were subjected to further screening to
      evaluate their probiotic potential, using a combination of in vitro and in vivo
      approaches. The majority of them showed high survival rates under in vitro
      simulated gastro-intestinal conditions, and positive antimicrobial activity
      against Salmonella enterica serovar Typhimurium, Listeria monocytogenes and
      enterotoxigenic Escherichia coli (ETEC) pathogens. Evaluation of antibiotic
      resistance to ampicillin, tetracycline, chloramphenicol, or erythromycin was also
      performed for all selected strains. Three L. coryniformis strains were selected
      as very good performers in the initial in vitro testing screens, they were
      antibiotic susceptible, as well as capable of inhibiting pathogen growth in
      vitro. Parallel screening employing the simplified model organism Caenorhabditis
      elegans, fed the Lactobacillus strains as a food source, revealed that one L.
      pentosus and one L. coryniformis strains significantly induced prolongevity
      effects and protection from pathogen-mediated infection. Moreover, both strains
      displayed adhesion to human intestinal epithelial Caco-2 cells and were able to
      outcompete foodborne pathogens for cell adhesion. Overall, these results are
      suggestive of beneficial features for novel LAB strains, which renders them
      promising candidates as starters for the manufacturing of fermented table olives
      with probiotic added value.

PMID- 29643849
TI  - Insights Into Vaginal Bacterial Communities and Metabolic Profiles of Chlamydia
      trachomatis Infection: Positioning Between Eubiosis and Dysbiosis.
AB  - The vaginal microbiota plays a crucial role in maintaining the health and
      functioning of the female genital tract, preventing the colonization of
      urogenital pathogens and sexually transmitted infections. In this study, we
      characterized the vaginal bacterial communities and the metabolome associated to
      Chlamydia trachomatis infection (CT: 20 women), compared to healthy condition (H:
      22 women) and bacterial vaginosis (BV: 19 women). A microarray-based tool
      (VaginArray), implemented with a real-time PCR for Gardnerella vaginalis, was
      used to determine the vaginal bacterial composition, whereas the metabolic
      profiles were assessed by a proton-based nuclear magnetic resonance (1H-NMR)
      spectroscopy. CT infection was characterized by bacterial and metabolic
      signatures similar to healthy condition, even though higher amounts of
      Lactobacillus iners, as well as depletion of some amino acids, biogenic amines,
      and succinate marked CT infection. Moreover, the frequency of Lactobacillus
      crispatus was higher in asymptomatic CT-positive patients than in women with CT
      correlated symptoms. We also confirmed the marked differences in the microbiome
      and metabolome between healthy and BV-affected women. In conclusion, we
      highlighted microbial and metabolic peculiarities of the vaginal ecosystem in the
      case of CT infection, even though further studies are needed to understand if the
      observed alterations precede the infection onset or if the pathogen itself
      perturbs the vaginal environment.

PMID- 29643850
TI  - A Perspective on the Potential Zoonotic Role of Streptococcus agalactiae:
      Searching for a Missing Link in Alternative Transmission Routes.

PMID- 29643851
TI  - Atomic Force Microscopy Provides New Mechanistic Insights into the Pathogenesis
      of Pemphigus.
AB  - Autoantibodies binding to the extracellular domains of desmoglein (Dsg) 3 and 1
      are critical in the pathogenesis of pemphigus by mechanisms leading to impaired
      function of desmosomes and blister formation in the epidermis and mucous
      membranes. Desmosomes are highly organized protein complexes which provide strong
      intercellular adhesion. Desmosomal cadherins such as Dsgs, proteins of the
      cadherin superfamily which interact via their extracellular domains in Ca2+
      dependent manner, are the transmembrane adhesion molecules clustered within
      desmosomes. Investigations on pemphigus cover a wide range of experimental
      approaches including biophysical methods. Especially atomic force microscopy
      (AFM) has recently been applied increasingly because it allows the analysis of
      native materials such as cultured cells and tissues under near-physiological
      conditions. AFM provides information about the mechanical properties of the
      sample together with detailed interaction analyses of adhesion molecules. With
      AFM, it was recently demonstrated that autoantibodies directly inhibit Dsg
      interactions on the surface of living keratinocytes, a phenomenon which has long
      been considered the main mechanism causing loss of cell cohesion in pemphigus. In
      addition, AFM allows to study how signaling pathways altered in pemphigus control
      binding properties of Dsgs. More general, AFM and other biophysical studies
      recently revealed the importance of keratin filaments for regulation of Dsg
      binding and keratinocyte mechanical properties. In this mini-review, we
      reevaluate AFM studies in pemphigus and keratinocyte research, recapitulate what
      is known about the interaction mechanisms of desmosomal cadherins and discuss the
      advantages and limitations of AFM in these regards.

PMID- 29643853
TI  - Gender Bias in Human Systemic Lupus Erythematosus: A Problem of Steroid Receptor
      Action?
AB  - Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease
      resulting from abnormal interactions between T and B cells. The acquisition of
      SLE is linked to genetic susceptibility, and diverse environmental agents can
      trigger disease onset in genetically susceptible individuals. However, the
      strongest risk factor for developing SLE is being female (9:1 female to male
      ratio). The female sex steroid, estradiol, working through its receptors,
      contributes to the gender bias in SLE although the mechanisms remain enigmatic.
      In a small clinical trial, monthly administration of the estrogen receptor
      (ERalpha) antagonist, ICI182,780 (fulvestrant), significantly reduced disease
      indicators in SLE patients. In order to identify changes that could account for
      improved disease status, the present study utilized fulvestrant (Faslodex) to
      block ERalpha action in cultured SLE T cells that were purified from blood
      samples collected from SLE patients (n = 18, median age 42 years) and healthy
      control females (n = 25, median age 46 years). The effects of ERalpha antagonism
      on estradiol-dependent gene expression and canonical signaling pathways were
      analyzed. Pathways that were significantly altered by addition of Faslodex
      included T helper (Th) cell differentiation, steroid receptor signaling
      [glucocorticoid receptor (GR), ESR1 (ERalpha)], ubiquitination, and sumoylation
      pathways. ERalpha protein expression was significantly lower (p < 0.018) in
      freshly isolated, resting SLE T cells suggesting ERalpha turnover is inherently
      faster in SLE T cells. In contrast, ERalpha/ERbeta mRNA and ERbeta protein levels
      were not significantly different between SLE and normal control T cell samples.
      Plasma estradiol levels did not differ (p > 0.05) between SLE patients and
      controls. A previously undetected interaction between GR and ERalpha signaling
      pathways suggests posttranslational modification of steroid receptors in SLE T
      cells may alter ERalpha/GR actions and contribute to the strong gender bias of
      this autoimmune disorder.

PMID- 29643854
TI  - The Role of Quinine-Responsive Taste Receptor Family 2 in Airway Immune Defense
      and Chronic Rhinosinusitis.
AB  - Background: Bitter (T2R) and sweet (T1R) taste receptors in the airway are
      important in innate immune defense, and variations in taste receptor
      functionality in one T2R (T2R38) correlate with disease status and disease
      severity in chronic rhinosinusitis (CRS). Quinine is a bitter compound that is an
      agonist for several T2Rs also expressed on sinonasal cells, but not for T2R38.
      Because of this property, quinine may stimulate innate immune defense mechanisms
      in the airway, and functional differences in quinine perception may be reflective
      of disease status in CRS. Methods: Demographic and taste intensity data were
      collected prospectively from CRS patients and non-CRS control subjects. Sinonasal
      tissue from patients undergoing rhinologic surgery was also collected and grown
      at an air-liquid interface (ALI). Nitric oxide (NO) production and dynamic
      regulation of ciliary beat frequency in response to quinine stimulation were
      assessed in vitro. Results: Quinine reliably increased ciliary beat frequency and
      NO production in ALI cultures in a manner consistent with T2R activation (p <
      0.01). Quinine taste intensity rating was performed in 328 CRS patients and 287
      control subjects demonstrating that CRS with nasal polyps (CRSwNP) patients rated
      quinine as significantly less intense than did control subjects. Conclusion:
      Quinine stimulates airway innate immune defenses by increasing ciliary beat
      frequency and stimulating NO production in a manner fitting with T2R activation.
      Patient variability in quinine sensitivity is observed in taste intensity
      ratings, and gustatory quinine "insensitivity" is associated with CRSwNP status.
      Thus, taste tests for quinine may be a biomarker for CRSwNP, and topical quinine
      has therapeutic potential as a stimulant of innate defenses.

PMID- 29643852
TI  - Innate Immune Responses in Leprosy.
AB  - Leprosy is an infectious disease that may present different clinical forms
      depending on host immune response to Mycobacterium leprae. Several studies have
      clarified the role of various T cell populations in leprosy; however, recent
      evidences suggest that local innate immune mechanisms are key determinants in
      driving the disease to its different clinical manifestations. Leprosy is an ideal
      model to study the immunoregulatory role of innate immune molecules and its
      interaction with nervous system, which can affect homeostasis and contribute to
      the development of inflammatory episodes during the course of the disease.
      Macrophages, dendritic cells, neutrophils, and keratinocytes are the major cell
      populations studied and the comprehension of the complex networking created by
      cytokine release, lipid and iron metabolism, as well as antimicrobial effector
      pathways might provide data that will help in the development of new strategies
      for leprosy management.

PMID- 29643855
TI  - Targeting Sphingosine Kinase Isoforms Effectively Reduces Growth and Survival of
      Neoplastic Mast Cells With D816V-KIT.
AB  - Mastocytosis is a disorder resulting from an abnormal mast cell (MC) accumulation
      in tissues that is often associated with the D816V mutation in KIT, the tyrosine
      kinase receptor for stem cell factor. Therapies available to treat aggressive
      presentations of mastocytosis are limited, thus exploration of novel
      pharmacological targets that reduce MC burden is desirable. Since increased
      generation of the lipid mediator sphingosine-1-phosphate (S1P) by sphingosine
      kinase (SPHK) has been linked to oncogenesis, we studied the involvement of the
      two SPHK isoforms (SPHK1 and SPHK2) in the regulation of neoplastic human MC
      growth. While SPHK2 inhibition prevented entry into the cell cycle in normal and
      neoplastic human MCs with minimal effect on cell survival, SPHK1 inhibition
      caused cell cycle arrest in G2/M and apoptosis, particularly in D816V-KIT MCs.
      This was mediated via activation of the DNA damage response (DDR) cascade,
      including phosphorylation of the checkpoint kinase 2 (CHK2), CHK2-mediated M
      phase inducer phosphatase 3 depletion, and p53 activation. Combination treatment
      of SPHK inhibitors with KIT inhibitors showed greater growth inhibition of D816V
      KIT MCs than either inhibitor alone. Furthermore, inhibition of SPHK isoforms
      reduced the number of malignant bone marrow MCs from patients with mastocytosis
      and the growth of D816V-KIT MCs in a xenograft mouse model. Our results reveal a
      role for SPHK isoforms in the regulation of growth and survival in normal and
      neoplastic MCs and suggest a regulatory function for SPHK1 in the DDR in MCs with
      KIT mutations. The findings also suggest that targeting the SPHK/S1P axis may
      provide an alternative to tyrosine kinase inhibitors, alone or in combination,
      for the treatment of aggressive mastocytosis and other hematological malignancies
      associated with the D816V-KIT mutation.

PMID- 29643856
TI  - The Contribution of Non-Professional Antigen-Presenting Cells to Immunity and
      Tolerance in the Liver.
AB  - The liver represents a unique organ biased toward a tolerogenic milieu. Due to
      its anatomical location, it is constantly exposed to microbial and food-derived
      antigens from the gut and thus equipped with a complex cellular network that
      ensures dampening T-cell responses. Within this cellular network, parenchymal
      cells (hepatocytes), non-parenchymal cells (liver sinusoidal endothelial cells
      and hepatic stellate cells), and immune cells contribute directly or indirectly
      to this process. Despite this refractory bias, the liver is capable of mounting
      efficient T-cell responses. How the various antigen-presenting cell (APC)
      populations contribute to this process and how they handle danger signals
      determine the outcome of the generated immune responses. Importantly, liver
      mounted responses convey consequences not only for the local but also to systemic
      immunity. Here, we discuss various aspects of antigen presentation and its
      consequences by the non-professional APCs in the liver microenvironment.

PMID- 29643857
TI  - A 17-kDa Fragment of Lactoferrin Associates With the Termination of Inflammation
      and Peptides Within Promote Resolution.
AB  - During the resolution of inflammation, macrophages engulf apoptotic
      polymorphonuclear cells (PMN) and can accumulate large numbers of their corpses.
      Here, we report that resolution phase macrophages acquire the neutrophil-derived
      glycoprotein lactoferrin (Lf) and fragments thereof in vivo and ex vivo. During
      the onset and resolving phases of inflammation in murine peritonitis and bovine
      mastitis, Lf fragments of 15 and 17 kDa occurred in various body fluids, and the
      murine fragmentation, accumulation, and release were mediated initially by
      neutrophils and later by efferocytic macrophages. The 17-kDa fragment contained
      two bioactive tripeptides, FKD and FKE that promoted resolution phase macrophage
      conversion to a pro-resolving phenotype. This resulted in a reduction in
      peritoneal macrophage numbers and an increase in the CD11blow subset of these
      cells. Moreover, FKE, but not FKD, peptides enhanced efferocytosis of apoptotic
      PMN, reduced TNFalpha and interleukin (IL)-6, and increased IL-10 secretion by
      lipopolysaccharide-stimulated macrophages ex vivo. In addition, FKE promoted
      neutrophil-mediated resolution at high concentrations (100 uM) by enhancing the
      formation of cytokine-scavenging aggregated NETs (tophi) at a low cellular
      density. Thus, PMN Lf is processed, acquired, and "recycled" by neutrophils and
      macrophages during inflammation resolution to generate fragments and peptides
      with paramount pro-resolving activities.

PMID- 29643858
TI  - Tobacco Transcription Factor NtbHLH123 Confers Tolerance to Cold Stress by
      Regulating the NtCBF Pathway and Reactive Oxygen Species Homeostasis.
AB  - Cold stress is a major environmental factor that impairs plant growth and
      development, geographic distribution, and crop productivity. The C-repeat binding
      factor (CBF) regulatory pathway has an essential role in response to cold stress.
      Here, we characterized a bHLH transcription factor from Nicotiana tabacum,
      NtbHLH123, in response to cold stress (4 degrees C). Overexpression of NtbHLH123
      enhanced cold tolerance in transgenic tobacco plants. Based on yeast one-hybrid,
      chromatin immunoprecipitation PCR, and transient expression analysis assays,
      NtbHLH123 binds directly to the G-box/E-box motifs in the promoter of the NtCBF
      genes and positively regulates their expression. Furthermore, NtbHLH123
      overexpressing plants showed lower electrolyte leakage, reduced malondialdehyde
      contents, H2O2 and reactive oxygen species (ROS) accumulation under cold stress,
      which contributed to alleviating oxidative damage to the cell membrane after cold
      stress treatment. And NtbHLH123 increased stress tolerance by improving the
      expression of a number of abiotic stress-responsive genes to mediate the ROS
      scavenging ability and other stress tolerance pathways. Taken together, we
      present a model suggesting that NtbHLH123 is a transcriptional activator that
      functions as a positive regulator of cold tolerance by activating NtCBF, ROS
      scavenging-related, and stress-responsive genes.

PMID- 29643859
TI  - Major Co-localized QTL for Plant Height, Branch Initiation Height, Stem Diameter,
      and Flowering Time in an Alien Introgression Derived Brassica napus DH
      Population.
AB  - Plant height (PH), branch initiation height (BIH), and stem diameter (SD) are
      three stem-related traits that play crucial roles in plant architecture and
      lodging resistance. Herein, we show one doubled haploid (DH) population obtained
      from a cross between Y689 (one Capsella bursa-pastoris derived Brassica napus
      intertribal introgression) and Westar (B. napus cultivar) that these traits were
      significantly positively correlated with one another and with flowering time
      (FT). Based on a high-density SNP map, a total of 102 additive quantitative trait
      loci (QTL) were identified across six environments. Seventy-two consensus QTL and
      49 unique QTL were identified using a two-round strategy of QTL meta-analysis.
      Notably, a total of 19 major QTL, including 11 novel ones, were detected for
      these traits, which comprised two QTL clusters on chromosomes A02 and A07.
      Conditional QTL mapping was performed to preliminarily evaluate the genetic basis
      (pleiotropy or tight linkage) of the co-localized QTL. In addition, QTL by
      environment interactions (QEI) mapping was performed to verify the additive QTL
      and estimate the QEI effect. In the genomic regions of all major QTL, orthologs
      of the genes involved in phytohormone biosynthesis, phytohormone signaling,
      flower development, and cell differentiation in Arabidopsis were proposed as
      candidate genes. Of these, BnaA02g02560, an ortholog of Arabidopsis GASA4, was
      suggested as a candidate gene for PH, SD, and FT; and BnaA02g08490, an ortholog
      of Arabidopsis GNL, was associated with PH, BIH and FT. These results provide
      useful information for further genetic studies on stem-related traits and plant
      growth adaptation.

PMID- 29643860
TI  - Seed and Foliar Application of Amino Acids Improve Variables of Nitrogen
      Metabolism and Productivity in Soybean Crop.
AB  - The application of amino acids in crops has been a common practice in recent
      years, although most of the time they are associated with products based on algae
      extracts or on fermented animal or vegetable wastes. However, little is known
      about the isolated effect of amino acids on the development of crops. Therefore,
      the objective of this research was to evaluate the effect of the application of
      isolated amino acids on the in some steps of the soybean nitrogen metabolism and
      on productivity. Experiments were carried out in a greenhouse and in the field
      with the application of the amino acids glutamate (Glu), phenylalanine (Phe),
      cysteine (Cys) and glycine (Gly) and as a set (Glu+Phe+Cys+Gly), as seed
      treatment (ST), as foliar application (FA) and both (ST+FA), at the V4 growth
      stage. Evaluations consisted of nitrate reductase and urease activities, nitrate,
      ureide, total amino acids and total nitrogen content in leaves, and productivity.
      The application of Glu to leaves, Cys as ST and a mixture of Glu+Cys+Phe+Gly as
      ST+FA in the greenhouse experiment increased the total amino acids content. In
      the field experiment all treatments increased the amino acid content in leaves.
      At the V6 stage in the field experiment, all modes of Gly application, Glu as ST
      and FA, Cys and Phe as ST+FA and Glu+Cys+Phe+Gly as FA increased the nitrate
      content in leaves. In the greenhouse, application of Cys and Phe as ST increased
      the production of soybean plants by at least 21%. The isolated application of
      Cys, Phe, Gly, Glu and the set of these amino acids as ST increased the
      productivity of soybean plants in the field experiment by at least 22%.

PMID- 29643861
TI  - "Targeted Sequencing by Gene Synteny," a New Strategy for Polyploid Species:
      Sequencing and Physical Structure of a Complex Sugarcane Region.
AB  - Sugarcane exhibits a complex genome mainly due to its aneuploid nature and high
      ploidy level, and sequencing of its genome poses a great challenge. Closely
      related species with well-assembled and annotated genomes can be used to help
      assemble complex genomes. Here, a stable quantitative trait locus (QTL) related
      to sugar accumulation in sorghum was successfully transferred to the sugarcane
      genome. Gene sequences related to this QTL were identified in silico from
      sugarcane transcriptome data, and molecular markers based on these sequences were
      developed to select bacterial artificial chromosome (BAC) clones from the
      sugarcane variety SP80-3280. Sixty-eight BAC clones containing at least two gene
      sequences associated with the sorghum QTL were sequenced using Pacific
      Biosciences (PacBio) technology. Twenty BAC sequences were found to be related to
      the syntenic region, of which nine were sufficient to represent this region. The
      strategy we propose is called "targeted sequencing by gene synteny," which is a
      simpler approach to understanding the genome structure of complex genomic regions
      associated with traits of interest.

PMID- 29643862
TI  - Comprehensive Characterization of Simple Sequence Repeats in Eggplant (Solanum
      melongena L.) Genome and Construction of a Web Resource.
AB  - We have characterized the simple sequence repeat (SSR) markers of the eggplant
      (Solanum melongena) using a recent high quality sequence of its whole genome. We
      found nearly 133,000 perfect SSRs, a density of 125.5 SSRs/Mbp, and also about
      178,400 imperfect SSRs. Of the perfect SSRs, 15.6% were complex, with two
      stretches of repeats separated by an intervening block of <100 nt. Di- and
      trinucleotide SSRs accounted, respectively, for 43 and 37% of the total. The SSRs
      were classified according to their number of repeats and overall length, and were
      assigned to their linkage group. We found 2,449 of the perfect SSRs in 2,086
      genes, with an overall density of 18.5 SSRs/Mbp across the gene space; 3,524
      imperfect SSRs were present in 2,924 genes at a density of 26.7 SSRs/Mbp.
      Putative functions were assigned via ontology to genes containing at least one
      SSR. Using this data we developed an "Eggplant Microsatellite DataBase" (EgMiDB)
      which permits identification of SSR markers in terms of their location on the
      genome, type of repeat (perfect vs. imperfect), motif type, sequence, repeat
      number and genomic/gene context. It also suggests forward and reverse primers. We
      employed an in silico PCR analysis to validate these SSR markers, using as
      templates two CDS sets and three assembled transcriptomes obtained from diverse
      eggplant accessions.

PMID- 29643864
TI  - A Method of High Throughput Monitoring Crop Physiology Using Chlorophyll
      Fluorescence and Multispectral Imaging.
AB  - We present a high throughput crop physiology condition monitoring system and
      corresponding monitoring method. The monitoring system can perform large-area
      chlorophyll fluorescence imaging and multispectral imaging. The monitoring method
      can determine the crop current condition continuously and non-destructively. We
      choose chlorophyll fluorescence parameters and relative reflectance of
      multispectral as the indicators of crop physiological status. Using tomato as
      experiment subject, the typical crop physiological stress, such as drought,
      nutrition deficiency and plant disease can be distinguished by the monitoring
      method. Furthermore, we have studied the correlation between the physiological
      indicators and the degree of stress. Besides realizing the continuous monitoring
      of crop physiology, the monitoring system and method provide the possibility of
      machine automatic diagnosis of the plant physiology. Highlights: A newly designed
      high throughput crop physiology monitoring system and the corresponding
      monitoring method are described in this study. Different types of stress can
      induce distinct fluorescence and spectral characteristics, which can be used to
      evaluate the physiological status of plants.

PMID- 29643863
TI  - Mutation in Rice Abscisic Acid2 Results in Cell Death, Enhanced Disease
      Resistance, Altered Seed Dormancy and Development.
AB  - Lesion mimic mutants display spontaneous cell death, and thus are valuable for
      understanding the molecular mechanism of cell death and disease resistance.
      Although a lot of such mutants have been characterized in rice, the relationship
      between lesion formation and abscisic acid (ABA) synthesis pathway is not
      reported. In the present study, we identified a rice mutant, lesion mimic mutant
      9150 (lmm9150), exhibiting spontaneous cell death, pre-harvest sprouting,
      enhanced growth, and resistance to rice bacterial and blast diseases. Cell death
      in the mutant was accompanied with excessive accumulation of H2O2. Enhanced
      disease resistance was associated with cell death and upregulation of defense
      related genes. Map-based cloning identified a G-to-A point mutation resulting in
      a D-to-N substitution at the amino acid position 110 of OsABA2 (LOC_Os03g59610)
      in lmm9150. Knock-out of OsABA2 through CRISPR/Cas9 led to phenotypes similar to
      those of lmm9150. Consistent with the function of OsABA2 in ABA biosynthesis, ABA
      level in the lmm9150 mutant was significantly reduced. Moreover, exogenous
      application of ABA could rescue all the mutant phenotypes of lmm9150. Taken
      together, our data linked ABA deficiency to cell death and provided insight into
      the role of ABA in rice disease resistance.

PMID- 29643865
TI  - Moonlighting Proteins and Their Role in the Control of Signaling
      Microenvironments, as Exemplified by cGMP and Phytosulfokine Receptor 1 (PSKR1).
AB  - Signal generating and processing complexes and changes in concentrations of
      messenger molecules such as calcium ions and cyclic nucleotides develop gradients
      that have critical roles in relaying messages within cells. Cytoplasmic contents
      are densely packed, and in plant cells this is compounded by the restricted
      cytoplasmic space. To function in such crowded spaces, scaffold proteins have
      evolved to keep key enzymes in the correct place to ensure ordered spatial and
      temporal and stimulus-specific message generation. Hence, throughout the
      cytoplasm there are gradients of messenger molecules that influence signaling
      processes. However, it is only recently becoming apparent that specific complexes
      involving receptor molecules can generate multiple signal gradients and enriched
      microenvironments around the cytoplasmic domains of the receptor that regulate
      downstream signaling. Such gradients or signal circuits can involve moonlighting
      proteins, so called because they can enable fine-tune signal cascades via cryptic
      additional functions that are just being defined. This perspective focuses on how
      enigmatic activity of moonlighting proteins potentially contributes to regional
      intracellular microenvironments. For instance, the proteins associated with
      moonlighting proteins that generate cyclic nucleotides may be regulated by cyclic
      nucleotide binding directly or indirectly. In this perspective, we discuss how
      generation of cyclic nucleotide-enriched microenvironments can promote and
      regulate signaling events. As an example, we use the phytosulfokine receptor
      (PSKR1), discuss the function of its domains and their mutual interactions and
      argue that this complex architecture and function enhances tuning of signals in
      microenvironments.

PMID- 29643867
TI  - Honest Errors and Self-Retraction should Not be Stigmatized or Penalized.

PMID- 29643868
TI  - Measuring Learning of Medical Students through 'Programmatic Assessment'.

PMID- 29643866
TI  - Joint Genomic Prediction of Canine Hip Dysplasia in UK and US Labrador
      Retrievers.
AB  - Canine hip dysplasia, a debilitating orthopedic disorder that leads to
      osteoarthritis and cartilage degeneration, is common in several large-sized dog
      breeds and shows moderate heritability suggesting that selection can reduce
      prevalence. Estimating genomic breeding values require large reference
      populations, which are expensive to genotype for development of genomic
      prediction tools. Combining datasets from different countries could be an option
      to help build larger reference datasets without incurring extra genotyping costs.
      Our objective was to evaluate genomic prediction based on a combination of UK and
      US datasets of genotyped dogs with records of Norberg angle scores, related to
      canine hip dysplasia. Prediction accuracies using a single population were 0.179
      and 0.290 for 1,179 and 242 UK and US Labrador Retrievers, respectively.
      Prediction accuracies changed to 0.189 and 0.260, with an increased bias of
      genomic breeding values when using a joint training set (biased upwards for the
      US population and downwards for the UK population). Our results show that in this
      study of canine hip dysplasia, little or no benefit was gained from using a joint
      training set as compared to using a single population as training set. We
      attribute this to differences in the genetic background of the two populations as
      well as the small sample size of the US dataset.

PMID- 29643869
TI  - Neurological complications are avoidable during CABG.
AB  - Objective: To review the incidence of stroke in patients undergoing CABG and the
      impact of a preventive strategy adopted at tertiary care unit of cardiac surgery.
      Methods: The data of all patients who underwent isolated CABG (N= 722) from July
      2016 to August 2017 at Faisalabad Institute of Cardiology was retrieved for this
      retrospective study. All operations were done on cardiopulmonary bypass and cold
      blood cardioplegia. Numeric data was summarized as Mean +/- Standard Deviation
      while categoric variables were summarized into frequency and percentage. Results:
      Mean age of patients was 53.83+/-8.8 years. Mean Parsonnet and Logistic EuroScore
      were 4.3+/-3.2 and 3.3+/-0.9 respectively. Forty nine patients (6.78%) had
      significant carotid artery disease. Mean number of grafts was 2.8+/-0.82.
      Diabetes was present in 27.8% patients. Neurological complications were noticed
      in 14 patients (1.94%) who included 12 permanent paralyses. Further subgroup
      analysis revealed that 67 patients who were operated by single clamp technique
      remained free of neurological complications. This is clinically remarkable
      finding but due to small population size it is statistically non- significant.
      Conclusion: The incidence of neurological complications can be reduced
      significantly by adopting the appropriate preventing measures. Use of Single
      Clamp technique may be the reasons of such a low incidence of stroke in this
      study.

PMID- 29643870
TI  - Therapeutic Endoscopy in Combination with Quadruple Therapy in Treating Bleeding
      Caused by Gastric Ulcer.
AB  - Objective: To analyze the efficacy of therapeutic endoscopy in combination with
      quadruple therapy in treating bleeding caused by gastric ulcer and investigate
      the factors inducing rebleeding. Methods: Two hundred and twelve patients with
      bleeding caused by gastric ulcer who were admitted to Binzhou People's Hospital,
      Shandong, China between April 2015 and April 2016 were selected as research
      subjects. The patients were randomly divided into a control group and an
      experimental group. Patients in the control group were treated by quadruple
      therapy, while patients in the observation group received therapeutic endoscopy
      treatment in addition to the same treatment as the control group. The treatment
      efficacy, adverse reaction, H pylori (Hp) clearance rate and rebleeding were
      compared between the two groups. Results: The effective rate of the observation
      group was 98.1%, which was significantly higher than that of the control group
      (80.2%), and the difference had statistical significance (P<0.05). The incidence
      of adverse reactions in the observation group was lower than that in the control
      group. The Hp clearance rate of the observation group was higher than that of the
      control group, and the difference had statistical significance (P<0.05). The
      multi-factor analysis on rebleeding suggested that whether therapeutic endoscopy
      was performed or not, hemoglobin level and presence of peptic ulcer stage A1 were
      independent risk factors. Conclusion: Endoscopic treatment in combination with
      quadruple therapy is better in the treatment of bleeding caused by gastric ulcer
      as compared to medical treatment alone. Patients with high-risk factors such as
      low content of hemoglobin and ulcer at stage A1 should be monitored more
      carefully to prevent the occurrence of rebleeding.

PMID- 29643871
TI  - An examination of the sexual functions of patients who underwent a gynecologic
      cancer operation and received brachytherapy.
AB  - Objective: This study was planned as a descriptive study for the purpose of
      examining the sexual functions of patients' who underwent a gynecological
      operation and received brachytherapy. Methods: The study was conducted with 118
      women who attended the Radiation Oncology Unit at Ege University Medical Faculty
      Hospital in Izmir Province for Gynecological Oncology follow-up, who participated
      voluntarily and were assigned using the random sampling method. The participants
      were married, sexually active, had a diagnosis of gynecologic cancer, underwent
      an operation and received brachytherapy for four months after the operation. The
      Individual Identification Form and Female Sexual Function Index (FSFI) were used
      as the data collection tools. Results: The average age of women who participated
      in study was 50.90+/-7.98 and 41.5% of them had completed primary school. About
      60% of the participants had cervical cancer and 69.5% had a total abdominal
      hysterectomy with bilateral salpingo-oopherectomy. The FSFI average score was
      determined to be 15.77+/-8.71. It was found that 97.5% of the participants
      received fewer than 30 points from the scale and these participants thus
      experienced sexual dysfunction. Conclusions: According to the findings obtained
      from the study, almost all thewomen that had an operation as a result of
      adiagnosis of gynecologic cancer and received brachytherapy experienced sexual
      dysfunction.

PMID- 29643872
TI  - Surgical Repair of post-infarction ventricular septal rupture: Determinants of
      operative mortality and survival outcome analysis.
AB  - Background and Objective: Ventricular septal rupture (VSR) is one of the fatal
      complications of myocardial infarction (MI). Surgery provides the maximum
      survival benefit. Our objective was to investigate the risk factors of surgical
      mortality and to do the survival analysis in the past six years at our hospital.
      Methods: All the patients operated at CPE Institute of Cardiology Multan
      Pakistan, between 2009 and 2015 for repair of post MI VSR were analysed
      retrospectively for demographics, comorbidities, operative and post operative
      outcomes. The primary outcome was 30 days mortality. The follow up was done till
      April 2017 and the follow up data was obtained from hospital records and by
      telephoning the patients. SPSS was used for statistical analysis. P value < 0.05
      was considered significant. Results: A total of 31 patients were operated for VSR
      repair with a mean age of 57.19+/-7.73 years. Eighteen patients also had a
      concomitant coronary artery bypass grafting (CABG). The operative mortality in
      this series was 25.8% Univariate analysis showed that pre-operative ejection
      fraction (E.F) (p value 0.010) and cardiogenic shock (p value 0.031) were a
      significant risk factors for operative mortality while on logistic regression
      analysis only the cardiogenic shock was found to be an independent risk factor
      for operative mortality with the odds ratio of 2.17. Low ejection fraction only
      acted as a confounding variable. The mean survival at six years was 34 months
      with a survival rate of 28.6%. The additional CABG did not confer any survival
      benefit. Conclusion: The patients in cardiogenic shock pre-operatively have a
      high operative mortality. Low ejection fraction (E.F) acts as a confounding
      factor. Concomitant CABG does not confer any survival benefit.

PMID- 29643873
TI  - Gastric emptying scintigraphy in postprandial distress syndrome.
AB  - Objective: To find out the pattern of gastric emptying scintigraphy (GES) in
      patients with post prandial distress syndrome (PDS). Methods: This study was
      carried out from January 2015 to July 2016 at Combined Military Hospital (CMH)
      Kharian and Nuclear Medical Centre (NMC) of Armed Forces Institute of Pathology
      (AFIP) Rawalpindi. Patient's inclusion criteria were dyspepsia of post prandial
      distress type for more than six months duration. Patients with dyspepsia due to
      epigastric pain syndrome and other organic disorder were excluded. Upper
      gastrointestinal endoscopy was performed in all patients to rules out organic
      causes. Four-hour Gastric emptying scintigraphy was carried out at NMC, AFIP.
      Results were compiled and statistical assessment was done by utilizing SPSS IBM
      22 version. Results: Thirty-eight patients were included in the study with age
      range from 15-72 years with mean age of 37.05+/-13.5 years. Males were 28(73.7%)
      and 10(26.7%) were female. Mean gastric retention with SD at one, two, three and
      four hours were 63 +/- 19.04, 37+/- 20.62, 19+/-16.66 and 10+/-12.73 percent
      respectively. Early gastric emptying was in 3(7.89%) and delayed gastric emptying
      at two and four hours was seen in 4(10.52%) and 12(32%) respectively. Seventeen
      (44%) of the patients had normal gastric emptying despite the classical symptoms
      of PDS. Conclusion: Gastric dysmotility in GES seen in half of the patients
      points some additional mechanism as well like gastric accommodation or visceral
      hypersensitivity in the patients with PDS.

PMID- 29643874
TI  - Effect of Erbium-yttrium, scandium, gallium and garnet (Er-YSGG) laser on the
      bond strength of lithium disilicate ceramics.
AB  - Objectives: To assess the bond strength of LD ceramics with resin composite
      material and surface conditioning using Er: YSGG laser and HF acid. Methods:
      Thirty LD ceramic (Emax, Ivoclar vivadent) discs were prepared using hot pressing
      technique and treated with hydroflouric acid (Group-1-HF acid) (9%) (n=10) and Er
      yttrium, scandium, gallium and garnet laser (Group-2-ER-YSGG laser) (Waterlase
      iPlus, 10 Hz and power of 0.5 W, pulse duration of 230 MUs) (n=10). Ten specimens
      were left untreated to be included as controls (Group-3-Control). All the
      specimens were treated with Adper Single Bond adhesive (3MESPE, St. Paul, MN,
      USA). Multicore buildups (3mmx3mm) were performed using a rubber mold on the
      ceramic surfaces and cured using LED light-curing unit for 140 sec. All specimens
      were tested using shear bond test and failure modes were assessed with a
      stereomicroscope and scanning electron microscope. Data was analysed using ANOVA
      and Tukey Kramer multiple comparisons test. Results: The maximum and minimum
      shear bond strength values were achieved in HF Acid specimens (Group-1) (28.15+/
      4.72 MPa) and control specimens (13.47+/- 3.14 MPa) respectively. Specimens
      treated with HF acid showed significantly higher bond strength in comparison to
      laser treated and control specimens (p<0.01). Laser treated specimens had
      significantly higher bond strength as compared to controls (p<0.01). Conclusions:
      Hydrofluoric (HF) acid treatment showed significantly better outcomes than YSGG
      laser surface treatment.

PMID- 29643875
TI  - Association of clinical and laboratory parameters with ambulatory arterial
      stiffness index in acromegaly patients.
AB  - Objective: In this study, we determined the relationship between the ambulatory
      arterial stiffness index (AASI) and clinical and laboratory parameters in
      patients with acromegaly. Methods: Sixty-five patients with acromegaly, who
      visited to Dicle University Medical Faculty Department of Endocrinology (33
      females and 32 males), were included in this study. The study control group
      consisted of 65 subjects. Demographic and clinical data were recorded. Laboratory
      data (complete blood count, blood urea nitrogen, creatinine, electrolytes,
      albumin, lipid profile, growth hormone [GH], insulin-like growth factor-1, and
      the 75-g oral glucose tolerance test) performed over the last year were
      evaluated. The AASI was obtained from 24-hour ambulatory blood pressure
      monitoring records of all patients. This study was completed in 15 months from
      2013 to 2015. Results: Twelve patients (18.4%) had diabetes and 21 patients (32%)
      had hypertension. The mean AASI value was 0.41 +/- 0.14. The mean AASI value in
      the control group was 0.25 +/- 0.09. Growth hormone (GH) levels were positively
      correlated with the AASI values. AASI values tended to be higher in hypertensive
      subjects than that in normotensive individuals. Conclusions: Our results show
      that the AASI value increased in patients with acromegaly, independent of the
      increase in blood pressure. The AASI was strongly dependent on the degree of the
      GH increase in patients with acromegaly and may have an important role predicting
      cardiovascular risk in patients with acromegaly.

PMID- 29643876
TI  - Clinical effects of single femoral nerve block in combination with general
      anesthesia on geriatric patients receiving total knee arthroplasty.
AB  - Objective: To evaluate the clinical effects of single femoral nerve block (sFNB)
      combined with general anesthesia on geriatric patients receiving unilateral total
      knee arthroplasty (UTKA). Methods: Sixty geriatric UTKA patients who were treated
      in The First People's Hospital of Changzhou from January 2015 to August 2015 were
      randomly divided into an sFNB + laryngeal mask airway (FLA) group, an sFNB +
      tracheal intubation (FGA) group and a tracheal intubation (GA) group. Their
      clinical parameters and indices were recorded. They were scored by the Visual
      Analogue Scale (VAS). Results: All patients completed this study. FLA and FGA
      groups used less propofol, remifentanil and fentanyl than GA group (P<0.01), with
      shorter recovery time and extubation time (P<0.05). Compared to GA group, FLA and
      FGA groups had lower systolic blood pressures at T3, T4 and T5 (P<0.05), and
      lower heart rates at T5 (P<0.05). FLA and FGA groups had fewer cases of adverse
      reactions after extubation (P<0.01). FLA group was less prone to irritating cough
      after extubation and pharyngeal pain than FGA and GA groups (P<0.01). The
      postoperative six hour and 24 hour VAS scores in resting state as well as the
      postoperative 24 hour and 48 hour scores in training state of FLA and FGA groups
      were lower than those of GA group (P<0.05). FLA and FGA groups used significantly
      lower times and total doses of patient-controlled intravenous analgesia pump.
      Conclusion: sFNB combined with general anesthesia, especially that using
      laryngeal mask, were superior to general anesthesia alone, which reduced recovery
      and extubation times, and decreased intraoperative and postoperative drug uses,
      postoperative early VAS score and adverse reactions.

PMID- 29643877
TI  - Comparison between primary closure with Limberg Flap versus open procedure in
      treatment of pilonidal sinus, in terms of frequency of post-operative wound
      infection.
AB  - Objective: Pilonidal sinus is a disorder of the sacrococcygeal region affecting
      younger individuals with a higher hair and weight distribution. Treatment
      involves the use of various surgical modalities, most of which are associated
      with a high rate of complications. Open procedure (OP) and Limberg Flap (LF) are
      two commonly performed surgical procedures for the correction of pilonidal sinus
      disease in our setup. The objective of our study was to compare the treatment of
      pilonidal sinus disease by primary closure with Limberg Flap verses Open
      procedure in terms of frequency of postoperative wound infection. Methods: The
      study is a randomized clinical trial (RCT) conducted at the department of
      surgery, military hospital, Rawalpindi, Pakistan. It was carried out over a
      period of 8 months from 16 February, 2015 to 16 September, 2015. Using
      consecutive non-probability sampling, a total of 60 patients were selected, 30 of
      whom underwent Limberg Flap procedure and the remaining 30 underwent open
      procedure. Postoperatively, observations for wound infection on date of discharge
      and then again on the various follow-up visits over the next 3 weeks. The data
      collected was then compared by applying the chi-square test, with p-value less
      than 0.05 considered statistically significant. Results: Our results showed that
      both primary closure with Limberg flap, and open procedure are comparable options
      in terms of wound infection. There was no statistical significance in the
      incidence of post operative infections, between the two surgeries. Conclusion: In
      terms of wound infection, both procedures are satisfactory surgical procedures
      for Pilonidal sinus disease.

PMID- 29643878
TI  - Is postmenopausal endometrial fluid collection alone a risk factor for
      endometrial cancer?
AB  - Objective: To determine the usefulness of single-layer, ultrasonographic
      measurement of endometrial fluid collection (EFC) volume to predict endometrial
      pathology in asymptomatic postmenopausal patients. Methods: One hundred fifty
      asymptomatic postmenopausal women were analysed retrospectively from January 2012
      to December 2016. After patients with endometrial hyperplasia/neoplasia were
      included in Group-I, and those with insufficient tissue, endometrial atrophy, or
      endometritis were included in Group-II; Groups one and two were compared with
      respect to primary (correlations between endometrial thickness and EFC volume)
      and secondary (correlations between demographic characteristics and EFC volume)
      outcomes. Results: There was no correlation between EFC volume and single-layer
      endometrial thickness (P = 0.36). Likewise, demographic characteristics were not
      related to EFC (P > 0.05). However, both EFC volume and single-layer endometrial
      thickness were thicker in Group-I compared to Group-II (4.8 +/- 1.9 mm vs. 3.7 +/
      2.5 mm; and 5.7 +/- 9.4 mm vs. 2.7 +/- 2.5 mm, respectively) (P values were <
      0.05). Conclusion: Although a cutoff value for endometrial thickness and EFC
      volume could not be recommended based on our study findings, it should be noted
      that 2% is a clinically significant rate of malignancy. Thus, postmenopausal
      patients with EFC should be evaluated for endometrial sampling.

PMID- 29643879
TI  - Transesophageal Echocardiography in Cardiogenic Embolic Cerebral Infarction.
AB  - Objective: To evaluate the diagnostic values of transesophageal echocardiography
      (TEE) and transthoracic echocardiography (TTE) in cardiogenic embolic cerebral
      infarction. Methods: Fifty patients with occult cerebral infarction who were
      admitted to the hospital between June 2015 and June 2016 were selected as
      research subjects. The patients were diagnosed by transesophageal
      echocardiography and transthoracic echocardiography. Diagnostic data were
      compared to analyze the values of the two diagnostic methods. Results: Sixteen
      out of fifty patients were diagnosed as cardiogenic embolic cerebral infarction
      by TEE (32%), including two cases of aortic plaques, six cases of atrial septal
      defect, two cases of atrial septal aneurysm, two cases of patent foramen ovale,
      one case of left atrial spontaneous echo contrast, one case of mitral prolapse
      and two case of mitral stenosis. Four cases were diagnosed as cardiogenic embolic
      cerebral infarction by TTE (8.0%), including one case of patent foramen ovale,
      one case of left atrial spontaneous echo contrast, one case of mitral prolapse
      and one case of mitral stenosis. The difference was statistically significant
      (P<0.05). The main difference of TEE and TTE was detection of aorta atheromatous
      plaques and atrial septal lesions. Aortic atheromatous plaques of two cases and
      atrial septal lesions of eight cases were missed in the diagnosis by TTE.
      Conclusion: Detection and diagnosis of cardiac embolic cerebral infarction with
      TEE is highly accurate and advantageous. Therefore, TEE is worth promotion and
      application.

PMID- 29643880
TI  - Intra-Operative Predictors of difficult cholecystectomy and Conversion to Open
      Cholecystectomy - A New Scoring System.
AB  - Objective: To evaluate the intra-operative scoring system to predict difficult
      cholecystectomy and conversion to open surgery. Methods: This descriptive study
      was conducted from March 2016 to August, 2016 in the Department of Surgery,
      Shalimar Hospital. The study recruited 120 patients of either gender, age greater
      than 18 years and indicated for laparoscopic cholecystectomy (LC). Intra
      operatively all patients were evaluated using the new scoring system. The scoring
      system included five aspects; appearance and adhesion of Gall Bladder (GB),
      distension or contracture degree of GB, ease in access, local or septic
      complications, and time required for cystic artery and duct identification. The
      scoring system ranges from 0 to 10, classified as score of <2 being considered
      easy, 2 to 4 moderate, 5-7 very difficult, and 8 to 10, extreme. Patient
      demographic data (i.e. age, gender), co-morbidities, intra-operative scores using
      the scoring system and conversion to open were recorded. The data was analysed
      using statistical analysis software SPSS (IBM). Results: Among one hundred and
      twenty participants, sixty seven percent were females and the mean age (years)
      was 43.05 +/- 14.16. Co-morbidities were present in twenty percent patients with
      eleven diagnosed with diabetes, six with hypertension and five with both
      hypertension and diabetes. The conversion rate to open surgery was 6.7%. The
      overall mean intra-operative scores were 3.52 +/- 2.23; however significant
      difference was seen in mean operative score of converted to open and those not
      converted to open (8.00 +/- 0.92 Vs. 3.20 V 1.92; p-value = 0.001). Among eight
      cases converted to open, three (37.5%) were in very difficult category while five
      (62.5%) were in extreme category. Moreover, age greater than 40 years and being
      diabetic were also the risk factors for conversion to open surgery. Conclusion:
      The new intra-operative scoring system is a valuable assessment tool to predict
      difficult laparoscopic cholecystectomy and conversion parameters to open surgery
      and its utility could improve patient's clinical outcome indicated for
      laparoscopic cholecystectomy.

PMID- 29643881
TI  - Urinary tract infections in the geriatric patients.
AB  - Objective: Urinary tract infections (UTI) are the second most common infection in
      geriatric population. This study investigated clinical findings, diagnostic
      approaches, complicating factors, prognosis, causative microorganisms and
      antimicrobial susceptibility in geriatric patients diagnosed with UTI. Methods: A
      total of 140 hospitalised patients with UTIs were evaluated within three years
      between January 2011-January 2015 at the Eskisehir Yunus Emre State Hospital. UTI
      diagnosed when there were systemic and urinary signs and symptoms and a positive
      dipstick test and urine culture result, leukocyte and CRP like serum parameters.
      Results: Among the studied patients, 41.4% had urological diseases, 20.7% had
      diabetes mellitus and 19.2% had neurological diseases. The most common symptoms
      and signs were fever, dysuria nausea/vomiting, general condition impairment,
      pyuria, haematuria. The laboratory values for CRP, ESR and leukocyte count were
      84 mg/dL, 56 mm/s and 11.9 (10^3MUL), with mean values being determined. Among
      patients having a urinary catheter (17.1%), 27.9% had a history of UTI, while
      29.3% had been hospitalised. Escherichia coli and Klebsiella pneumoniae were the
      most commonly identified microorganisms. The mean duration for hospitalisation
      was 7.6 days, while a 5% mortality rate was observed over the course of the
      disease. Conclusion: Because of the potential for serious complications and
      mortality, elderly patients with urinary tract infection, should receive
      immediate empirical treatment based on anamnesis, clinical evaluation and
      urinalysis and should be re-examined using results from cultures and antibiograms
      upon follow-up.

PMID- 29643882
TI  - Nerve growth factor in combination with Oxiracetam in the treatment of
      Hypertensive Cerebral Hemorrhage.
AB  - Objective: To compare the clinical efficacy of nerve growth factor (NGF) in
      combination with oxiracetam and single use of oxiracetam in the treatment of
      hypertensive cerebral hemorrhage. Methods: One hundred and forty patients with
      hypertensive cerebral hemorrhage who were admitted to the hospital from July 2015
      to September 2016 were selected as research subjects and randomly divided into a
      treatment group which was treated by NGF in combination with oxiracetam and a
      control group which was treated by oxiracetam only. The clinical efficacy was
      observed, and the death of both groups was recorded. Results: The National
      Institutes of Health Stroke Scale (NIHSS) score, Glasgow Coma Scale (GCS) score
      and limbs muscle force of both groups improved after treatment, and the
      improvement of the treatment was superior to that of the control group,
      suggesting a significant difference (P<0.05). The reduction of serum inflammatory
      factor level of the treatment group was much larger than that of the control
      group after treatment, and the difference had statistical significance (P<0.05).
      The survival analysis suggested that the survival rates of the two groups had a
      statistically significant difference (P<0.05). Conclusion: NGF in combination
      with oxiracetam is significantly effective in treating hypertensive cerebral
      hemorrhage as it can apparently recover neurologic impairment and limbs muscle
      force. The therapy has important clinical application values.

PMID- 29643883
TI  - Comparison of volume and frequency advancement feeding protocols in very low
      birth weight neonates.
AB  - Objective: To determine the outcomes in very low birth weight (VLBW) neonates
      receiving volume advancement versus frequency advancement feeding protocols.
      Methods: This controlled clinical trial was conducted in Children Hospital Multan
      within duration of 6 months from February 2017 to August 2017. VLBW neonates
      having weight < 1500 g at the time of birth were included. The protocol for
      frequency advancement (FA) group was to give 1 ml/kg human or pre-formula milk
      after every 8 hours and in volume advancement (VA) group after every 3 hours
      initially. After three days, in FA group duration of feeds was decreased
      gradually from 8 to 2 hours and feed volume of 10 ml.kg-1.day-1 until full
      recommended dose of feeding i.e. 150 ml.kg-1.day-1 reached. While in VA group,
      volume of 20 ml.kg-1.day-1 was given until full-recommended dose of feeding
      reached. Days to achieve full feed, weight gain, and length of hospital stay were
      primary study outcomes. Results: Baseline weight of neonates was 1148 (111) grams
      in VA 1179 (106) grams in FA groups (p-value 0.18). In VA group, full feed was
      achieved in 11.04 (2.38) days versus 15.76 (2.48) days in FA group (P-value
      <0.001). Duration of IV fluid therapy were 13.5 (8.4) days in FA group versus 9.4
      (7.6) in VA group (p-value <0.001). Moreover weight gain at the end of feeding
      protocol was significantly higher in VA group 1440 (78) grams versus 1284 (99)
      grams in FA group (P-value <0.001). Necrotizing entero-colitis occurred in only
      one neonate that was belonging to volume advancement group. Conclusion: Volume
      advancement (VA) feeding is better as compared to frequency advancement (FA)
      feeding in very low birth weight neonates.

PMID- 29643884
TI  - Brachdactyly Instigated as a Result of Mutation in GDF5 and NOG Genes in
      Pakistani Population.
AB  - Objectives: Brachdactyly a genetic disorder associated with the abnormal
      development of metacarpals, phalanges or both which results in the shortening of
      hands and feet. Mutations in the contributing genes has been recognized with the
      majority of the investigated syndromic form of brachdactyly. The current study
      was proposed to examine mutation in NOG and GDF5 genes in a Pakistani family.
      Methods: Poly Acrylamide Gel Electrophoresis and Polymerase Chain Reaction was
      used for the genomic screening and linkage analysis to observe the mutation in
      genes. The samples were collected from Luckki Marwat district, KPK, while the
      research study was conducted in the department of Biochemistry, Quaid-I-Azam
      University, Islamabad, Pakistan. Results: After survey, family was identified
      with brachdactyly type A2 and investigated a heterozygous arginine to glutamine
      exchange in the growth demarcation factor 5 in all the victim persons. Different
      types of skeletal dysplasia resulted due to mutation in the GDF5 genes. Novel
      GDF5 genes mutations were reported with distinct limb malformation and sequencing
      of coding region revealed that the mildly affected individuals were heterozygous
      while the harshly affected individuals were homozygous. Conclusion: The current
      study reported the genetic variability and concluded that the Brachdacytyly type
      A2 and type B2 resulted due to mutation in GDF5 and NOG genes respectively. A new
      subtype of brachydactyly (BDB2) was instigated as a result of novel mutations in
      NOG. The mutation has been reported for the first time in Pakistani population
      and especially in Pushtoon ethnic population.

PMID- 29643885
TI  - ANCA associated vasculitis in patients from Saudi Arabia.
AB  - Objective: To explore clinical and laboratory features, therapy and outcome of
      antineutrophil cytoplasmic antibodies (ANCA) associated vasculitis (AAV) patients
      from our tertiary care center. Methods: This study of AAV patients seen in
      Rheumatology clinics at King Khalid University hospital (KKUH), King Saud
      University, Riyadh during the period 1990-2014 was carried out retrospectively.
      Demographic, clinical, haematological and immunological parameters along with
      therapy, complications and outcome were retrieved from patients' medical charts.
      Different characteristics were compared between the three groups of AAV; GPA
      (Granulomatosis with polyangiitis), MPA (Microscopic polyangiitis) and EGPA
      (Eosinophilic granulomatosis with polyangiitis). Results: We identified 34 AAV
      patients (21 males: 13 females; 31 Saudis: 3 non-Saudis) comprising of 23 GPA, 2
      MPA and 9 EGPA cases. The mean age of onset was 42.1+/-17.6 years (range 11-75)
      and mean duration of disease was 8.7+/- 5.1 years (range 1-20). The most
      frequently affected system was pulmonary in all AAV (73.5%), GPA (65.2%) and EGPA
      (100%) while it was renal in MPA (100%) patients. Ophthalmological and upper
      airways involvement was higher in GPA. Neurological involvement was higher in
      EGPA (p<0.05). ANCA were detected in 79.4% of AAV patients, of them c-ANCA were
      77.8% and p-ANCA 22.2%. ANCA was positive in 91.3% GPA, 100% MPA and 44.4% EGPA
      patients. In GPA c-ANCA were detected in 80.9% and p-ANCA in 17.4%, in MPA, c
      ANCA were detected in 50% and p-ANCA in 50%, in EGPA, c-ANCA were observed in 75%
      and p-ANCA in 25%. GPA patients had PR3 specificity in 93.3%, and MPO in 6.7%,
      PR3 was present in all MPA patients (100%), while EGPA patients had MPO (100%).
      Therapy administered were corticosteroids (100%), intravenous cyclophosphamide
      (58.8%), azathioprine (50%) and rituximab (11.8%). Infections were noted in
      29.4%. Conclusions: The 10-year survival in our AAV patients was 95%. ANCA
      pattern was similar to Caucasian AAV patients and different from Japanese and
      Chinese AAV patients.

PMID- 29643886
TI  - An examination of anxiety levels of nursing students caring for patients in
      terminal period.
AB  - Objective: To investigate the anxiety levels of the nursing students who are
      caring for the patients in the terminal period and to determine whether there is
      a difference between 3rd, 4th grade in this direction. Methods: A 40-item "State
      and Trait Anxiety Scale" was used together with the questionnaire on "Determining
      the Level of Anxiety Levels of Nursing Students Caring for the Patient at the
      Terminal Period" for determining the data. Results: The mean scores and standard
      deviations of all students from the state and trait anxiety scales were
      respectively 41.95+/-5.06, 48.15+/-5.44. Averages of 3rd state anxiety scale
      score was 42.03 +/- 5.26, trait anxiety scale averages were 48.08 +/- 5.59;
      Averages of 4th state anxiety scale score was 41.85 +/- 4.83, trait anxiety scale
      averages were 48.24 +/- 5.30. Conclusion: In our study, it was found that there
      wasn't significant difference between the 3rd, 4th grade students related to ill
      patient care in terms of high level of state and trait anxiety during
      communication and patient care. The state and trait anxiety scores of the
      students in both grades were found to be higher than the average scores of the
      scale's previous applications.

PMID- 29643887
TI  - Liver histology in asymptomatic Hepatitis-C virus positive blood donors.
AB  - Objective: To assess the Histological alteration of liver in asymptomatic HCV PCR
      positive family blood donors. Methods: This is a prospective cross sectional
      study carried out at Blood Transfusion Services, Clinical & Molecular Laboratory
      and Pakistan Health Research Council, Jinnah Postgraduate Medical Centre, Karachi
      from January 2011 to December 2016. One hundred thirteen (113) Anti HCV and HCV
      RNA positive family blood donors with normal or slightly raised ALT during three
      consecutive bimonthly visits were included. After taking consent liver biopsy was
      done to see the histopathological changes in these study participants. The
      software program SPSS for windows (Ver.19) was utilized for all statistical
      analysis. Results: One hundred thirteen blood donors who were Anti HCV and HCV
      RNA positive were included. Ninety eight were male and 15 Female with a mean age
      of 32.3+/-6.94 years. Nineteen (16.8%) had significant inflammation of grade 2-3.
      Nine (8.0%) had significant fibrosis and steatosis was seen in 65 (57.5%) cases.
      Cirrhosis or advanced liver disease was not found in this series. Conclusion: HCV
      infected individual with normal ALT level having good physical health, without
      any sign of advanced liver disease on ultrasonography and routine laboratory
      investigation like AST, Gamma GT, Alkaline Phosphatase, serum albumin, A/G ratio,
      platelet count and PT, INR might be highly helpful to predict mild or progressive
      liver disease. Ultimately it reduces the need of liver biopsy, an invasive
      procedure having significant complications.

PMID- 29643888
TI  - Spectrum of complications of severe DKA in children in pediatric Intensive Care
      Unit.
AB  - Objectives: To describe the spectrum of complications of Diabetic Ketoacidosis
      (DKA) observed in children admitted with severe DKA. Methods: Retrospective
      review of the medical records of all children admitted with the diagnosis of
      severe DKA in Pediatric Intensive Care Unit (PICU) of the Aga Khan University
      Hospital, from January 2010 to December 2015 was done. Data was collected on a
      structured proforma and descriptive statistics were applied. Results: Total 37
      children were admitted with complicated DKA (1.9% of total PICU admission with
      1.8% in 2010 and 3.4% in 2015). Mean age of study population was 8.1+/-4.6 years
      and 70% were females (26/37). Mean Prism III score was 9.4+/-6, mean GCS on
      presentation was 11+/-3.8 and mean lowest pH was 7.00+/-0.15. Complications
      observed included hyperchloremia (35.94%), hypokalemia (30.81%), hyponatremia
      (26.70%), cerebral edema (16.43%), shock (13.35%), acute kidney injury (10.27%),
      arrhythmias (3.8%), and thrombotic thrombocytopenic purpura (5.4%), while one
      patient had myocarditis and ARDS each. 13/37 children (35%) needed inotropic
      support, 11/37 (30%) required mechanical ventilation while only one patient
      required renal replacement therapy. Two patients (5.4%) died during their PICU
      stay. Conclusion: Hyperchloremia and other electrolyte abnormalities, cerebral
      edema and AKI are the most common complications of severe DKA.

PMID- 29643889
TI  - Therapeutic effects of visual standard channel combined with F4.8 visual puncture
      super-mini percutaneous nephrolithotomy on multiple renal calculi.
AB  - Objective: To evaluate the therapeutic effects of visual standard channel
      combined with F4.8 visual puncture super-mini percutaneous nephrolithotomy (SMP)
      on multiple renal calculi. Methods: The clinical data of 46 patients with
      multiple renal calculi treated in Affiliated Hospital of Hebei University from
      October 2015 to September 2016 were retrospectively analyzed. There were 28 males
      and 18 females aged from 25 to 65 years old, with an average of 42.6. The stone
      diameters were 3.0-5.2 cm, (4.3 +/- 0.8) cm on average. F4.8 visual puncture
      assisted balloon expansion was used to establish a standard channel. After
      visible stones were removed through nephroscopy combined with ultrasound
      lithotripsy, the stones of other parts were treated through F4.8 visual puncture
      SMP with holmium laser. Indices such as the total time of channel establishment,
      surgical time, decreased value of hemoglobin, phase-I stone clearance rate and
      surgical complications were summarized. Results: Single standard channel was
      successfully established in all cases with the assistance of F4.8 visual
      puncture, of whom 24 were combined with a single microchannel, 16 were combined
      with double microchannels, and six were combined with three microchannels. All
      patients were placed with nephrostomy tube which was not placed in the
      microchannels. Both F5 double J tubes were placed after surgery. The time for
      establishing a standard channel through F4.8 visual puncture was (6.8 +/- 1.8)
      min, and that for establishing a single F4.8 visual puncture microchannel was
      (4.5 +/- 0.9) min. The surgical time was (92 +/- 15) min. The phase-I stone
      clearance rate was 91.3% (42/46), and the decreased value of hemoglobin was
      (12.21 +/- 2.5) g/L. There were 8 cases of postoperative fever which was relieved
      after anti-inflammatory treatment. Four cases had 0.5-0.8 cm of stone residue in
      the lower calyx, and all stones were discharged one month after surgery by in
      vitro shock wave lithotripsy combined with position nephrolithotomy, without
      stone streets, delayed bleeding, peripheral organ damage or urethral injury.
      Conclusion: Combining visual standard channel with F4.8 visual puncture SMP for
      the treatment of multiple renal calculi had the advantages of reducing the number
      of large channels, high rate of stone clearance, safety and reliability and mild
      complications. The established F4.8 visual puncture channel was safer and more
      accurate.

PMID- 29643890
TI  - Perceived social support in pregnant adolescents in Mersin area in Turkey.
AB  - Objective: The study examines the level and source of perceived social support in
      pregnant adolescents and the factors related to their perception of social
      support. Methods: This descriptive study was conducted with the voluntary
      participation of 127 adolescent pregnant females who visited the Gynecology and
      Pediatric Hospital in Mersin, Turkey. The data were collected based on the
      participants' self-expression, using the Socio-demographic Information Form and
      Multidimensional Scale of the Perceived Social Support. Results: The average age
      of the pregnant adolescents was 18 years. Approximately one-fifth of all
      participant females were either illiterate or had dropped out of the primary
      school. All pregnant adolescents were housewives with a low economic status.
      Findings pertaining to the participants'fertility showed that 69.3% were
      primiparous, 24.4% had at least one living child. The mean score for pregnant
      adolescents' perception of social support was 50.79+/-8.72. The mean score on the
      subscales was 23.32+/-3.23 for family support; 16.17+/-4.35 for friend support;
      and 12.29 +/- 5.54 for special person support. Conclusion: Pregnant adolescents
      had a low perception of social support. Families were found to be the most common
      source of social support available to pregnant adolescents, and they lacked the
      support from their friends and other special people.

PMID- 29643891
TI  - Assessment of Freshwater Springs, Associated Diseases and Indigenous Perception
      in Ghizer, Gilgit-Baltistan, Pakistan.
AB  - Objective: To assess the quality of freshwater aquifers (springs) associated
      diseases, and indigenous perception in Ghizer, Gilgit-Baltistan. Methods: This
      was a cross-sectional study conducted at the department of environmental science,
      Karakoram International University Gilgit after approval from departmental
      research committee. In order to get the most accurate results, 18 water samples
      in triplicates were collected according to our lab own set of sampling standard
      operating procedures (SOPs) using pre-sterilized bottles of 100 ml from June 2016
      to August 2016 along with associated diseases record and structured interviews
      from indigenous population. For physicochemical and microbial assessment, samples
      were tested before five hours after collection and associated diseases and
      indigenous perception was analyzed using descriptive statistical techniques.
      Results: Findings revealed that levels of pH, EC, phosphates, TDS, and nitrite,
      fall within WHO standards except nitrate, temperature and turbidity. The highest
      concentration (mgL-1+/- SE) of Hg in Barkolti and Barsat springs were (0.01+/
      0.005) and (0.02+/-0.001) while Zn was (0.04+/-0.02) respectively. The
      concentration of Cu in Barkolti spring was (0.2+/- 0.03) while in Barsat spring
      below the detection level. The concentration of Cd, Pb, Cr, and Fe in both
      springs fall within WHO permissible limits. The mean value of E. coli recorded in
      both Barkolti and Barsat aquifers were (1.08cfu +/-0.45) and (2.11cfu+/-0.56)
      respectively. The prevalence of water-associated diseases recorded in the order
      diarrhea, dysentery, typhoid, cholera, hepatitis and their incidence increases at
      high peak in summer. Irrespective of physicochemical and microbial components,
      indigenous population believed that the spring water has curative properties.
      Conclusions: Physiochemical and microbial parameters of spring's water fall
      within WHO standards except nitrate, turbidity, temperature, and E. coli, and
      incidence of certain associated diseases. However, indigenous population is
      unaware about the fact and believed that spring water very safe.

PMID- 29643892
TI  - Association of In-hospital outcome of Acute Kidney Injury (AKI) with etiology
      among newborns at a tertiary care unit.
AB  - Objective: To determine association of in-hospital outcome of AKI with etiology
      in newborns at a tertiary care hospital. Methods: This descriptive cross
      sectional study was conducted at Department of Pediatric Neonatology, The
      Children's Hospital and Institute of the Child Health, Multan by using non
      probability purposive sampling technique from June 2016 to June 2017. A total of
      101 newborns diagnosed with acute kidney injury were registered. Etiological
      factors were assessed and these patients were followed till discharge to monitor
      in-hospital outcomes. Results: Of these 101 newborns, 75 (74.3%) were boys while
      26 (25.7%) were girls. Mean age of these newborns was 7.59 +/- 6.13 days (range;
      1 day to 28 days). Mean age of the boys was 5.73 +/- 7.20 days while that of
      girls was 6.77 +/- 6.16 days. (p=0.515). Mean weight of these neonates was
      2545.05 +/- 600.42 grams (range; 1000 grams to 4000 grams). Mean serum potassium
      level was 4.94 +/- 0.92 mgEq/L ranging from 3.1 mgEq/L to 7.0 mgEq/L. Mean urea
      level was 73.35 +/- 27.65 mg/dl ranging from 18 mg/dl to 206 mg/dl. Mean serum
      creatinine level was 1.98 +/- 0.27 mg/dl, ranging from 1.6 mg/dl to 2.8 mg/dl.
      Mean serum sodium level was 145.72 +/- 12.64 mgEq/L ranging from 126 to 166
      mEq/L. Eighty one (80.2%) were term babies while 20 (19.8%) were pre-term babies.
      Of these 101 study cases, 29 (28.7%) delivered vaginally while 72 (71.3%) through
      cesarean section. Delayed crying was noted in 48 (47.5%), dehydration 13 (12.9%),
      sepsis in 36 (35.6%) and renal malformation in only 4%. Neonatal mortality in
      these patients was 15 (14.9%) while 86 (85.1%) were discharged from hospital
      after recovery. Conclusion: Acute kidney disease in newborns is associated with
      significant disease morbidity and mortality with asphyxia and sepsis are the main
      etiological factors responsible. It is predominantly more common in boys compared
      with girls. Mortality rate was high in our study and it was significantly
      associated with female gender. Mortality was also associated with elevated serum
      sodium and urea level.

PMID- 29643893
TI  - Impact of depressed skull fracture surgery on outcome of head injury patients.
AB  - Objective: To assess outcomes in surgically managed patients with depressed skull
      fractures and associated moderate to severe head injury. Methods: The study was
      conducted in the Department of Neurosurgery Jinnah Postgraduate Medical Centre,
      Karachi, from January 2016 to December 2017. We analyzed 90 patients with
      depressed skull fracture managed surgically from January 2015 to December 2016.
      The patients selected for this study belonged to all age groups with clinically
      palpable depressed skull fracture confirmed by CT brain with bone window. Outcome
      was assessed by Glasgow outcome score. Results: Total 90 patients were included
      in the study. Sixty (66.7%) were male and 30 (33.3%) were female with mean age of
      years 27.58+11.329. Among 90 patients, 38.8% were aged between 21 and 30 years.
      Road traffic accident was seen in 72 (80%) patients. The commonest site of
      fracture was frontal region in 50 patients (55.6%). GCS improved post operatively
      on comparison to preoperative. Five patients expired. Conclusion: Depressed skull
      fracture is common neuro surgical issue. Timely surgical management gives
      excellent results by decreasing morbidity and mortality.

PMID- 29643894
TI  - Characteristics of clinical drugs for elderly chronic heart failure complicated
      with different degrees of renal insufficiency.
AB  - Objective: To investigate the characteristics of clinical therapeutic drugs in
      elderly chronic heart failure (CHF) patients complicated with different degrees
      of renal insufficiency. Methods: The elderly patients who were hospitalized from
      October 2010 to October 2015 in our hospital due to CHF for the first time were
      selected by means of retrospective case collection. The glomerular filtration
      rate was estimated by using the Modification of Diet in Renal Disease (MDRD)
      Study equation. The patients were divided into a group with normal renal
      function, a group with slight decrease in renal function, and a group with
      moderate and severe decrease in renal function. Statistical analysis was made to
      compare the characteristics of clinical drugs for the three groups. Results:
      Compared with the normal renal function group and the slight decrease group,
      ACEIs and beta-blockers were less used in the moderate and severe decrease group,
      but diuretics and spironolactone were more used (P<0.05). Compared with the
      normal renal function group, the use rate of ACEIs was low whereas that of
      diuretics was high (P<0.05). Conclusion: ACEIs and beta-blockers were barely
      employed to treat elderly CHF patients complicated with renal insufficiency, but
      diuretics and spironolactone were frequently utilized.

PMID- 29643895
TI  - Expression analysis of glyoxalase I gene among patients of diabetic retinopathy.
AB  - Objectives: To study expression of glyoxalase I in patients of diabetic
      retinopathy. Methods: This cross-sectional comparative study was conducted at
      Centre for Research in Experimental and Applied Medicine (CREAM), Department of
      Biochemistry and Molecular Biology, Army Medical College, Rawalpindi in
      collaboration with Armed Forces Institute of Ophthalmology (AFIO) from January
      2015 to November 2015. Sampling technique was non- probability purposive
      sampling. Total 60 subjects were enrolled in two groups. Group-I comprised 30
      patients of diabetic retinopathy and Group-II of 30 normal healthy controls.
      Clinical and demographic data was collected and fasting venous blood samples (2
      ml) were drawn. RNA was extracted and subjected to cDNA synthesis. Expression
      analysis for glyoxalase I was carried out and relative quantification done by
      double delta Ct method. Results: Mean age of the patients was 61.30 +/-7.06 years
      and mean age of controls was 59.60 +/- 6.43 years. There were 17 (56.7%) males
      and 13 (43.3%) females in Group-I while Group-II comprised 14 (46.7%) males and
      16 (53.3%) females. There was down regulation of glyoxalase I among patients of
      diabetic retinopathy in comparison with controls when relative gene expression
      was calculated. Conclusion: Down regulation of glyoxalase I in patients of
      diabetic retinopathy suggests it to be a contributory factor in the development
      of disease.

PMID- 29643896
TI  - Potential Drug-Drug Interactions among Patients prescriptions collected from
      Medicine Out-patient Setting.
AB  - Objective: To identify and evaluate the frequency, severity, mechanism and common
      pairs of drug-drug interactions (DDIs) in prescriptions by consultants in
      medicine outpatient department. Methods: This cross sectional descriptive study
      was done by Pharmacology department of Bahria University Medical & Dental College
      (BUMDC) in medicine outpatient department (OPD) of a private hospital in Karachi
      from December 2015 to January 2016. A total of 220 prescriptions written by
      consultants were collected. Medications given with patient's diagnosis were
      recorded. Drugs were analyzed for interactions by utilizing Medscape drug
      interaction checker, drugs.com checker and stockley's drug interactions index.
      Two hundred eleven prescriptions were selected while remaining were excluded from
      the study because of unavailability of the prescribed drugs in the drug
      interaction checkers. Results: In 211 prescriptions, two common diagnoses were
      diabetes mellitus (28.43%) and hypertension (27.96%). A total of 978 medications
      were given. Mean number of medications per prescription was 4.6. A total of 369
      drug-drug interactions were identified in 211 prescriptions (175%). They were
      serious 4.33%, significant 66.12% and minor 29.53%. Pharmacokinetic and
      pharmacodynamic interactions were 37.94% and 51.21% respectively while 10.84% had
      unknown mechanism. Number wise common pairs of DDIs were Omeprazole-Losartan (S),
      Gabapentine- Acetaminophen (M), Losartan-Diclofenac (S). Conclusion: The
      frequency of DDIs is found to be too high in prescriptions of consultants from
      medicine OPD of a private hospital in Karachi. Significant drug-drug interactions
      were more and mostly caused by Pharmacodynamic mechanism. Number wise evaluation
      showed three common pairs of drugs involved in interactions.

PMID- 29643897
TI  - The effect of preoperative stoma site marking on quality of life.
AB  - Objective: The objective of the study was to determine the effect of preoperative
      stoma site marking on the health- related quality of life (HRQOL). Methods: A
      nonrandomized, quasi-experimental design was used for the study performed from
      June 2013 to August 2014. The study sample (n:60) included patients for whom a
      stoma was opened after a planned colorectal surgery. The City of Hope Quality of
      Life-Ostomy Questionnaire (COHQOL-OQ) was used to measure HRQOL. Results: The
      mean age of the participants in the experimental group was 53.5+/-12.83, 18(60%)
      had colostomies, mean BMI was 25.46 +/- 4.25 and mean age of that of the control
      group was 58.00 +/- 14.22, 19(63.3%) had colostomies, mean BMI was 25.28 +/-
      5.00. A comparison of the two groups indicates that the sixth-month total score
      of the patients in the experimental group on (COHQOL-OQ) is higher than that of
      the control group (p<0.05). Conclusions: The study results demonstrated that
      patient who underwent stoma site marking reported higher HRQOL than those who did
      not.

PMID- 29643898
TI  - To determine correlation between biochemical parameters of nutritional status
      with disease severity in HCV related liver cirrhosis.
AB  - Objective: To identify correlation between biochemical parameters of nutritional
      status with disease severity in HCV related liver cirrhosis in patients attending
      tertiary care hospital. Methods: Total 259 HCV related liver cirrhosis patients
      who attended the outpatient department of KRL Hospital, Islamabad from June 2016
      to January 2018 were included in this cross-sectional study. HCV status was
      confirmed with PCR. Cirrhosis was pre-established by ultrasound, while cirrhosis
      severity was gauged by CTP score. Biochemical parameters for nutrition status
      included serum albumin, creatinine, cholesterol, LDL, HDL, triglycerides,
      hemoglobin, ferritin, sodium, potassium, magnesium and calcium. Other demographic
      and clinical data were also recorded. Results: The mean age of patients was 58.73
      +/- 6.04 years with 57.1% being males. The average BMI was 22.72 +/- 1.69 kg/m2.
      Majority patients i.e. 123 (47.5%) belonged to CTP-A, 67 (25.9%) were in CTP-B
      and 69 (26.6%) in CTP-C groups. Significant negative correlations of cirrhosis
      severity were established with BMI, albumin, creatinine, cholesterol, LDL, TG,
      HDL, hemoglobin, sodium and magnesium indicative of malnutrition. Analysis of
      biochemical parameters amongst individual cirrhosis groups revealed significant
      negative correlation across the same factors in group CTP-C, while CTP-A
      correlated positively with these parameters. The only significant correlation
      found in CTP-B was with albumin, HDL, hemoglobin, sodium and magnesium.
      Conclusion: Considering limitations of standard ways alone to assess malnutrition
      in liver cirrhosis, biochemical parameters are valid to aid in diagnosing
      malnutrition.

PMID- 29643899
TI  - Influence of Apelin-13 on osteoporosis in Type-2 diabetes mellitus: A clinical
      study.
AB  - Objective: To investigate the relationship between serum level of Apelin-13 and
      bone mineral density (BMD) as well as other parameters, and determine the
      influence of Apelin-13 on osteoporosis in patients with Type-2 diabetes mellitus.
      Methods: Seventy-six patients with Type-2 diabetes mellitus were recruited from
      Department of Endocrinology of our hospital between January 2013 and July2017.
      The clinical data, including age, gender, height, weight, body mass index (BMI)
      and disease duration were recorded for all patients. Blood sample was collected
      for measurement of Apelin-13, Procollagen type-I N propeptide (PINP) and Cross
      linked carboxy terminal telopeptide of type-I collagen (ICTP), and BMD was tested
      with a dual-energy X-ray absorptiometry scanner. Results: The patients were
      divided into three groups, in which 19 patients were assigned in osteoporosis
      group, 25 in osteopenia group and 32 in normal group. The level of Apelin-13 in
      osteoporosis group was significantly lower than that in osteopenia and normal
      groups (p<0.05), and the value in osteopenia group was significant lower than
      that in normal group (p<0.05). Correlation analysis showed in the included
      patients the level of Apelin-13 was positively correlated to the value of BMD and
      PINP (p<0.05), but negatively correlated to age and ICTP (p<0.05). Conclusion: In
      conclusion, this study demonstrated that there was a close relationship among
      Apelin-13, BMD, ICTP and PINP, and Apelin-13 plays an important role in the
      occurrence of osteoporosis in patients with Type-2 diabetes mellitus.

PMID- 29643900
TI  - Measuring assessment standards in undergraduate medical programs: Development and
      validation of AIM tool.
AB  - Objective: To develop a tool to evaluate faculty perceptions of assessment
      quality in an undergraduate medical program. Methods: The Assessment
      Implementation Measure (AIM) tool was developed by a mixed method approach. A
      preliminary questionnaire developed through literature review was submitted to a
      panel of 10 medical education experts for a three-round 'Modified Delphi
      technique'. Panel agreement of > 75% was considered the criterion for inclusion
      of items in the questionnaire. Cognitive pre-testing of five faculty members was
      conducted. Pilot study was done with 30 randomly selected faculty members.
      Content validity index (CVI) was calculated for individual items (I-CVI) and
      composite scale (S-CVI). Cronbach's alpha was calculated to determine the
      internal consistency reliability of the tool. Results: The final AIM tool had 30
      items after the Delphi process. S-CVI was 0.98 with the S-CVI/Avg method and 0.86
      by S-CVI/UA method, suggesting good content validity. Cut-off value of < 0.9 I
      CVI was taken as criterion for item deletion. Cognitive pre-testing revealed good
      item interpretation. Cronbach's alpha calculated for the AIM was 0.9, whereas
      Cronbach's alpha for the four domains ranged from 0.67 to 0.80. Conclusions:
      'AIM' is a relevant and useful instrument with good content validity and
      reliability of results, and may be used to evaluate the teachers' perceptions
      about assessment quality.

PMID- 29643901
TI  - Evaluation of the effect of Retrograde Intrarenal Surgery with Myo-Inositol
      Oxygenase.
AB  - Objective: To investigate the effect of retrograde intra-renal surgery (RIRS) on
      kidneys using the myo-inositol oxygenase (MIOX) enzyme. MIOX is a renal tubular
      specific novel marker for the early diagnosis of acute kidney injury. Methods: A
      total of twenty seven individuals that had undergone RIRS to treat kidney stones
      were included in the study. Biochemical tests were performed on serum samples
      collected immediately before RIRS (hour 0) and at the 6th and 24th hours after
      the surgery. Results: The creatinine value at hour 6 was lower than the baseline
      (hour 0) value (p = 0.0305). Cystatin C at hour 6 was lower than the value
      measured at hour 24 (p = 0.0142). Similarly, MIOX was lower at hour 6 compared to
      hour 24 (p = 0.0214). MIOX/creatinine at hour 6 was lower than the value
      calculated at hour 24 (p = 0.0348). The basal values of MIOX and creatinine were
      found to have a positive correlation (correlation coefficient r = 0.5946, p =
      0.0035). Conclusions: Similar to the serum creatinine, the serum MIOX level
      provides information about kidney functions. RIRS was confirmed to be a safe
      procedure for the treatment of acute kidney injury with no negative effects on
      the kidneys.

PMID- 29643902
TI  - Is there difference in chronic pain after Suture and Stapler fixation method of
      mesh in Ventral Hernia? Is stapler fixation method quicker? A randomized
      controlled trial.
AB  - Background & Objective: Chronic pain occurs in 20-30% of patients after hernia
      surgery. As a consequence of this chronic pain, almost one third of patients have
      limitations in daily activities. Frequency and severity of this pain varies with
      different techniques of hernia repair. The objective of this study was to compare
      polypropylene suture and skin staples for securing mesh in uncomplicated ventral
      hernioplasty in terms of acute and chronic postoperative pain and to compare the
      time taken for mesh fixation between polypropylene sutures and skin stapler in
      ventral hernioplasty. Methods: This study was conducted in Surgery Department of
      Dow University Hospital, Dow University of Health Sciences, Ojha Campus and
      included 53 patients from Jan 2015 to Dec 2016, after taking informed consent.
      All patients were operated under general anesthesia by the same surgical team.
      Patients were randomized into two groups; in one group mesh fixed with 2/0
      polypropylene suture while in other group mesh stapler was used. Time taken to
      apply mesh was noted in minutes from laying the mesh over anterior rectus sheath
      to completion of fixation by either method. The severity of post-operative pain
      was measured with VAS (1-10) after one week, one month and after one year after
      surgery. Data was analysed using SPSS version 17. Results: Patient
      characteristics and operative outcome were similar in the two groups and
      statistically non-significant in both. Early postoperative pain was more after
      suture fixation but it was not statistically significant. Mean +/- SD pain score
      was after one week 3.47+/-2.7 after sutures while 2.91+/-1.88 after stapler.
      After four weeks, 0.40+/-0.49 after suture while 0.35+/-0.48 after stapler
      fixation. In both study groups 30-34% of the patients felt some pain in follow-up
      after one year. Severity of pain was 0.60+/-0.62 after suture while 1.65+/-1.94
      after stapler fixation which is statistically significant as well (p<0.007). Mean
      operative time was 15.33+/-6.33 minutes for suture fixation while 1.56+/-0.41
      minutes for fixation by staples, p-value < 0.001. Conclusion: The method of
      fixation does not appear to cause significant difference in early post-operative
      pain but chronic pain is more after stapler fixation of mesh. However, operative
      time was reduced significantly in staple fixation group as compared to suture
      fixation group.

PMID- 29643903
TI  - Effectiveness of case based cultural competency among nurses working in private
      hospitals of Bangkok, Thailand: A Quasi-experimental study.
AB  - Objectives: To evaluate the effect of case based cultural competency level and
      its factors affecting on nurse job in two private hospitals of Bangkok, Thailand.
      Methods: This was a quasi-experimental study implemented the cased-based cultural
      competent intervention in two private hospitals of Thailand in 2015. One hundred
      sixty six nurses from two control and intervention private hospitals through
      simple random selection method were selected for this study. Data was collected
      at the beginning of study (pre-test), immediately after the intervention and
      after two months of intervention (post-test). Tool was pretested, validated and
      piloted before to conduct study. Results: Total 166 nurses were included in this
      study. The characteristics among the study participants were similar between both
      hospitals at the baseline and found statistically non-significant (p= > 0.05).
      However, after the intervention the cultural knowledge, attitude and practice
      competency score levels have significantly increased among the nurses in the
      intervention group as compared to control group (p= < 0.05). Conclusion: Study
      has concluded that an intervention has positively affected on cultural knowledge,
      practice and attitude competency among nurses working in private hospital of
      Bangkok Thailand.

PMID- 29643904
TI  - Assessment of collaborative problem solving skills in Undergraduate Medical
      Students at Ziauddin College of Medicine, Karachi.
AB  - Objective: Collaborative Problem Solving Empirical Progressions from the
      Assessment and Teaching of 21st Century Skills (ATC21S) framework were used to
      determine the level of collaborative problem solving skills (CPS) in first,
      second and third year MBBS students at Ziauddin College of Medicine during
      Problem-Based Learning (PBL) sessions. Variations based on gender and roles were
      studied. Methods: It is an analytical comparative cross-sectional study in which
      seven PBL groups were selected per year by non-probability convenient sampling.
      Data was collected using the Collaborative Problem Solving Five Strands Empirical
      Progressions by the primary investigator through observation of the students
      during PBL sessions. Duration of study was six months. Results: We found that in
      our students, development of social dimension skills is facilitated to a greater
      extent than the development of cognitive dimension skills through the process of
      PBL. These skills are generally better developed in the leader compared to the
      scribe and members in a group. They are also more developed in females compared
      to males. Modification in them is also observed as the year's progress.
      Conclusion: Although PBLs facilitate development of CPS skills' progression
      however in our curriculum, PBLs mainly focus on social skills development and
      have less emphasis on cognitive skill development. Thus, hybrid instructional
      strategies with components from TBL and mentorship are recommended for better
      development of CPS skills.

PMID- 29643905
TI  - Comparison of application values of CT and MRI in the diagnosis of early Lacunar
      Infarction.
AB  - Objective: To analyze and compare the values of computed tomography (CT) and
      magnetic resonance imaging (MRI) in the diagnosis of early lacunar infarction.
      Methods: Eighty-eight patients with early lacunar infarction who were admitted to
      the hospital were selected as research subjects, and all of them underwent MRI
      and CT. The study was conducted at our hospital between May 2015 to July 2016.
      Results: Four hundred and forty-one lesions were detected by MRI, and 145 were
      detected by CT. Most of the lesions were located at the thalamus, frontal lobe
      and parietal lobe. The detection rate of small lesions with a diameter less than
      5 cm using MRI was significantly higher than that with CT, and the difference had
      statistical significance (P<0.05). Forty-nine cases who reached hospital within
      six hours were scanned in which no images were observed by CT, while small flake
      like or spotted images were observed in 47 cases by MRI. The efficacy of MRI in
      displaying early lesions and micro lesions was superior to that of CT.
      Conclusion: In the diagnosis of early lacunar infarction, the detection rate of
      lesions with MRI is significantly higher than that with CT. MRI can clearly
      display the specific conditions of lesions, which is worth clinical promotion.

PMID- 29643906
TI  - Radiolological predictors of recurrence of chronic subdural hematoma.
AB  - Objective: Chronic subdural hematoma is one of the most common clinical entities
      encountered in daily neurosurgical practice. Considerable recurrence rates have
      been reported for chronic subdural hematoma following surgical evacuation. Many
      studies have suggested various radiological factors that may be associated with
      the recurrence of CSDH. However, the results are inconsistent. This study focuses
      on determining the radiological factors predictive of chronic subdural hematoma
      recurrence. Methods: A retrospective analysis of 113 patients diagnosed with
      chronic subdural hematoma who were surgically treated between August 2013 and
      December 2014 was performed. The radiological features were analyzed to clarify
      the correlation between these radiological factors and postoperative recurrence
      of chronic subdural hematoma. Results: Twenty patients (17.7%) experienced
      recurrence. Chronic subdural hematoma recurrence was found to be significantly
      associated (p<0.05) with preoperative hematoma thickness >= 20 mm. Midline shift,
      hematoma density and bilaterality were not significantly associated with
      recurrence. Post operative drainage also significantly (p<0.05) reduced chronic
      subdural hematoma recurrence. Conclusion: Preoperative hematoma thickness >= 20
      mm is an independent predictor of recurrence of chronic subdural hematoma.
      Postoperative drainage also significantly reduces chronic subdural hematoma
      recurrence.

PMID- 29643907
TI  - Fixation of unstable distal radius fractures by using expandable Intramedullary
      nailing system in adult patients.
AB  - Objective: To present our experience on intramedullary nailing device Sonoma Wrx
      (Sonoma Orthopedic Products Inc., Santa Rosa, CA, USA) used for internal fixation
      of extra-articular or simple intra-articular distal radius fractures in adult
      population. Methods: This study was conducted from February 2011 to October 2016.
      A total of 48 patients (mean age 47.3+/-5.6 years, 35.4% females) with distal
      radius fracture, who underwent intramedullary distal radius fixation by using
      Sonoma Wrx were included in this retrospective study. Clinical outcome measures
      (range of motion [ROM], visual analog scale [VAS]), functional outcomes
      (Disabilities of the Arm, Shoulder and Hand [DASH] score and Gartland-Werley
      score), radiographic scores (Stewart score) and parameters (radial inclination,
      volar tilt, radial height, radio-ulnar variance) and complications were
      evaluated. Results: The total surgery time was 24.3+/-2.3 minutes. Patients were
      followed up for 24.7+/-3.4 weeks. Complete fracture union was obtained at 5.5+/
      0.9 weeks. The postoperative low VAS pain score (1.6+/-0.93) and high ROM values
      (76.7 degrees  for extension, 78.5 degrees  for supination, 80.1 degrees  for
      flexion, and 82.3 degrees  for pronation) indicated a very good clinical outcome.
      DASH score of 8.3+/-1.5 and Gartland-Werley score of 2.8+/-4.1 showed good
      functional outcome. The radiographic Stewart score was 1.0+/-1.2. Radial
      inclination, volar tilt, and radial height significantly increased (p<0.001), and
      radio-ulnar variance decreased (p=0.001) with surgery. No postoperative
      complication was recorded in 40 patients (83.3%). Conclusions: Sonoma Wrx, which
      is an expansible intramedullary elastic locking distal radius nail, offers a good
      alternative technique for internal fixation of unstable distal radius fractures
      with the advantage of minimum soft-tissue dissection and related postoperative
      complications.

PMID- 29643908
TI  - Lack of association of statin use with vitamin D levels in a hospital based
      population of type 2 diabetes mellitus patients.
AB  - Objective: To investigate the relationship of statins (drug given to reduce serum
      levels of LDL-cholesterol) on vitamin D levels of Pakistani type 2 diabetes
      mellitus (DM) patients in a hospital in Karachi. Methods: In a cross-sectional
      survey, 312 consecutive patients with type 2 DM (219 males and 93 females, age 22
      70 years) were recruited with informed consent. A questionnaire was administered
      to find out whether they were statin users or non-users. Serum was analyzed for
      concentrations of 25(OH) vitamin D [25(OH)D] and other related biomarkers such as
      serum cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, phosphate and
      calcium using kit methods. Multiple Linear Regression was used to evaluate
      association of statin use with serum levels of vitamin D while adjusting for
      related covariates including duration of statin use, duration of type 2 DM and
      smoking. Results: Mean concentrations of serum cholesterol, and LDL-cholesterol
      were lower among statin users compared to statin non-users (P < 0.01), while HDL
      cholesterol levels were higher (P<0.01). No relationship was observed between
      statin use and serum levels of vitamin D (P=0.768), when adjusted for age,
      gender, BMI, duration of type 2 DM, smoking, serum cholesterol and LDL
      cholesterol. The adjusted regression coefficient (beta) and standard error
      [SE(beta)] for statin use duration were 0.012 (0.042), when serum levels of
      vitamin D was taken as an outcome. Conclusion: Lack of association was found
      between statin use and vitamin D levels in a hospital-based population of
      Pakistani patients with type 2 DM.

PMID- 29643909
TI  - Hyperlipidemia and hyper glycaemia in Breast Cancer Patients is related to
      disease stage.
AB  - Objective: The study was designed to determine the hyperlipidemia in breast
      cancer of patients at disease presentation, without any treatment and to
      correlate these variations with disease stage. Methods: This cross sectional
      study was conducted at Liaquat National teaching hospital in Karachi from 2006 to
      2011, Age and family history of 208 breast cancer patients with infiltrating
      Ductal Carcinoma were compared with 176 matched control subjects. Married females
      were selected, with children and short breast feeding period. Cancer stage I-III
      was considered for the study and patients were grouped on the basis of Tumor
      grade, Tumor size, lymph node metastasis and disease free survival. Disease
      staging was based on tumor size and lymph node metastasis. Biochemical
      estimations included variations in random blood glucose level and lipid profile.
      Results: Lipid profile and random blood glucose level were found significantly
      high (p<0.05) compared to control subjects. Hyperlipidemia was significantly high
      in breast cancer patients with lymph node metastasis. On increase in tumor grade
      I to II, increase in total cholesterol (4%), LDL-cholesterol 23% and 11% increase
      in triglycerides was observed. On Tumor size increase from <=2 to 2.5cm, increase
      observed in blood random glucose level was (4%), total cholesterol (1.7%)
      triglycerides (2%) and LDL (3%) whereas HDL was (2%) low. These variations remain
      insignificant on further increase in tumor size and grade. Conclusion: Study
      suggests that variation in lipid profile and blood random glucose level is
      associated with disease stage. No independent correlation of hyperlipidemia and
      hyperglycemia was developed with disease free survival.

PMID- 29643910
TI  - Role of Mitogen-Activated Protein Kinases in the Formation of Hypertrophic Scar
      with Model of Lipopolysaccharide Stimulated Skin Fibroblast Cells.
AB  - Objective: Hypertrophic scar is common in burn patients, but treating result
      could not meet the expectation of the patients and doctors. We have found that
      certain concentration level of lipopolysaccharide (LPS) stimulated normal
      fibroblast cells have statistically similar with fibroblast cells from
      hypertrophic scar on the phenotype level, and with this work we are trying to
      figure out which Mitogen-Activated Protein Kinase (MAPK) is affected and how it
      is affected. Methods: Experiments were conducted in May, 2017 at the first
      affiliated hospital of the Chinese PLA General Hospital, Beijing, China. We have
      cultured the cell line of human skin fibroblast cells and randomly divided cells
      into four groups: control group and three stimulation groups. We have rebuilt the
      LPS stimulated model of skin fibroblast cells in hypertrophic scar based on our
      previous work. Experimental groups were stimulated with 0.1ug/mL LPS
      concentration for 24 hours, 48 hours, and 72 hours, respectively. Then we
      performed western blot analysis of Erk, p-Erk, JNK, p-JNK, p38 and p-p38. We
      performed statistical analysis with SPSS 15.0. Results: LPS can up regulate the
      MAPK/p38 pathway (p<0.05) and down regulate the MAPK/Erk and MAPK/JNK pathways
      (p<0.05). The changes of phosphorylated protein are time-related, with longer
      stimulation duration, significant difference is increased (p<0.05). Conclusion:
      MAPKs can play an important role in the formation of hypertrophic scar in the
      skin. Early intervention through the MAPKs could be a promising target in the
      prevention of the formation of hypertrophic scar.

PMID- 29643911
TI  - Pars plana vitrectomy in vitreous hemorrhage with or without Intravitreal
      Bevacizumab a comparative overview.
AB  - Objective: To compare the success in patients having vitreous hemorrhage
      undergoing pars plana vitrectomy with or without preoperative intravitreal
      injection of Bevacizumab. Methods: This Randomized controlled trial was conducted
      at Department of Ophthalmology, Jinnah Postgraduate Medical Centre. Karachi.
      Duration of study was six months from January 2010 to June 2010. In this study 56
      patients of advanced diabetic eye disease were divided into two groups. Patients
      in Group-A underwent three ports pars plana vitrectomy with preoperative
      intravitreal injection of Bevacizumab (Avastin) 1.25mg/0.05ml, 3.5mm from the
      limbus seven days before surgery and in Group-B patients underwent vitrectomy
      without preoperative intravitreal Bevacizumab (Avastin). Intraoperative bleeding
      was monitored in both groups and was graded as no bleeding, mild bleeding and
      severe bleeding. The results were statistically analyzed through computer
      software SPSS 17. Results: Twenty eight patients in Group-A who were given an
      injection of intravitreal Bevacizumab (Avastin) before surgery, intraoperative
      bleeding monitored was, no bleeding in 17 cases (60.7%), mild was observed in 6
      cases (21.4%) and severe bleeding requiring diathermy to stop was observed in
      only 5 cases (17.9%). 28 patients in Group-B that underwent surgery without
      Avastin no bleeding was observed in only 2 cases (7.1%), mild in 6 cases (21.4%)
      and severe in 20 cases (71.4%). Conclusions: Intravitreal injection of
      Bevacizumab (Avastin) was effective before vitrectomy in the surgical management
      of Advanced Diabetic Eye disease.

PMID- 29643912
TI  - Association of RAGE gene polymorphism with Type-2 diabetes mellitus in local
      population.
AB  - Objectives: Type-2 diabetes mellitus (T2DM) is an endocrine disease having a
      significant genetic component. Polymorphisms of many genes may affect hereditary
      vulnerability of the disease that is characterized by insulin resistance and
      islet disorder. As the genetic basis of T2DM can vary between ethnic groups, it
      is important to investigate the genetic link of T2DM in Pakistani populace. This
      study was aimed to assess the association of receptor for advanced glycation end
      product (RAGE) gene polymorphism (-429T>C) with Type-2 diabetes mellitus within
      local populace. Methods: Genomic DNA was isolated by following kit protocol.
      Genotyping of the RAGE gene was studied by PCR-RFLP on genomic DNA. All research
      work was done in molecular biochemistry laboratory (MBL), University of
      Agriculture Faisalabad and Postgraduate Laboratory, The University of Faisalabad,
      Pakistan from December 2016 to July 2017. Results: We found distribution of 
      429T>C genotypes between T2DM and healthy controls as 24.7% (tt), 24.7% (Tt) and
      50.7% (TT). The outcomes were highly compatible statistically. Conclusion: The
      techniques of PCR and RFLP when performed simultaneously can be helpful in
      tracing vital information regarding polymorphism of AGE receptor.

PMID- 29643913
TI  - Hair Dye poisoning: "An early intervention".
AB  - The use of hair dye has been emerging worldwide however usage of
      Paraphenylenediamine (PPD) in making hair dye is generally restricted to
      underdeveloped and developing countries. In particular, prevalence of accidental
      and suicidal ingestion is more in low socioeconomic areas. The spectra of hair
      dye toxicity is wide, however, it presents more commonly with severe angioedema
      of face and neck leading to respiratory failure, rhabdomyolysis complicating into
      acute kidney injury, myocarditis and acute liver injury. Here we present a unique
      case of PPD poisoning in a young female presented with laryngeal edema and marked
      rhabdomyolysis. Preemptive shifting to Critical care unit and elective
      endotracheal intubation for air way patency obviated the need of tracheostomy and
      precluded its related complications. Moreover, aggressive intravenous hydration
      prevented from renal failure despite markedly raised Creatine phospho kinase
      (CPK) levels.

PMID- 29643914
TI  - Author-based journal selection system that helps authors save time in article
      submission.
AB  - Submission to journals takes a lot of time and format related submission
      requirements vary greatly from one journal to another. Lack of time and
      motivation in academia reduces scientific outputs and demotivates researchers.
      Author-based journal selection system (ABJSS) is a platform for pooling
      manuscripts conceived to minimize the time spent for manuscript submission and to
      increase scientific output. The system will provide two types of account:
      "Author" and "Journal Administrator". Each account type will have its own
      abilities and permissions. The ABJJS system is an ongoing project that will be
      designed in cooperation with IT experts and academicians and it will be presented
      to the scientific world as soon as it secures sufficient support.

PMID- 29643915
TI  - Prognostic Significance of Blood, Serum, and Ascites Parameters in Patients with
      Malignant Peritoneal Mesothelioma or Peritoneal Carcinomatosis.
AB  - To determine effects of the biochemical and cytological properties of blood,
      serum, and ascites on survival of patients with malignant peritoneal effusion
      (MPeE), including malignant peritoneal mesothelioma (MPeM) and peritoneal
      carcinomatosis (PC), we conducted a retrospective study of patients with MPeE and
      healthy controls. Potential prognostic factors were identified as follows: age,
      sex, blood neutrophil-to-lymphocyte ratio (NLR), serum parameters, ascites
      parameters, serum-ascites albumin gradient, and the ascites-serum LDH ratio.
      Compared to those of the control group, serum albumin levels were significantly
      lower, and the NLR and serum LDH levels were significantly higher in the MPeE
      group. Overall survival (OS) was longer in patients with MPeM compared to that in
      patients with PC. Compared with patients in the MPeM, patients with PC had higher
      NLRs, ascites glucose levels, serum-ascites albumin gradients, and serum LDH
      levels. In contrast, their ascites albumin levels and ascites-serum LDH ratios
      were lower. Univariate analyses indicated that the NLR, serum LDH levels, ascites
      LDH levels, ascites coenocyte levels, and the ascites coenocyte-to-monocyte
      ratios affected the OS. Multivariate analyses identified only serum and ascites
      LDH levels as independent prognostic factors.

PMID- 29643916
TI  - Antireflux Metal Stent for Initial Treatment of Malignant Distal Biliary
      Obstruction.
AB  - Objectives: To compare the use of an antireflux metal stent (ARMS) with that of a
      conventional covered self-expandable metal stent (c-CSEMS) for initial stenting
      of malignant distal biliary obstruction (MDBO). Materials and Methods: We
      retrospectively investigated 59 consecutive patients with unresectable MDBO
      undergoing initial endoscopic biliary drainage. ARMS was used in 32 patients and
      c-CSEMS in 27. Technical success, functional success, complications, causes of
      recurrent biliary obstruction (RBO), time to RBO (TRBO), and reintervention were
      compared between the groups. Results: Stent placement was technically successful
      in all patients. There were no significant intergroup differences in functional
      success (ARMS [96.9%] versus c-CSEMS [96.2%]), complications (6.2 versus 7.4%),
      and RBO (48.4 versus 42.3%). Food impaction was significantly less frequent for
      ARMS than for c-CSEMS (P = 0.037), but TRBO did not differ significantly between
      the groups (log-rank test, P = 0.967). The median TRBO was 180.0 [interquartile
      range (IQR), 114.0-349.0] days for ARMS and 137.0 [IQR, 87.0-442.0] days for c
      CSEMS. In both groups, reintervention for RBO was successfully completed in all
      patients thus treated. Conclusion: ARMS offers no advantage for initial stent
      placement, but food impaction is significantly prevented by the antireflux valve.

PMID- 29643917
TI  - Predictive and Prognostic Implications of Mutation Profiling and Microsatellite
      Instability Status in Patients with Metastatic Colorectal Carcinoma.
AB  - To investigate whether mutation profiling and microsatellite instability (MSI)
      status were associated with clinicopathological features and the prognosis in
      metastatic colorectal cancer (mCRC), mutations in RAS (including KRAS, NRAS, and
      HRAS) and BRAF were determined by Sanger sequencing. Tumor mismatch repair
      proteins and MSI status were examined using immunohistochemistry and polymerase
      chain reaction, respectively. The clinical value of these abnormalities was
      statistically analyzed, and prognostic value of different treatment regimens was
      also evaluated. Among 461 mCRC patients, mutations in RAS, BRAF, and MSI-high
      (MSI-H) status were observed in 45.3% (209/461), 5.6% (26/461), and 6.5% (30/461)
      of cases, respectively. Brain metastasis and high carcinoembryonic antigen level
      were highly correlated with KRAS mutation (P = 0.011 and P < 0.001), and tumors
      from females or located in the right colon tended to harbor BRAF mutation (P =
      0.039 and P = 0.001). RAS/BRAF mutations may predict brain and/or lung
      metastases. Although neither clinical nor prognostic importance of MSI status was
      identified in our study, KRAS and BRAF mutations were demonstrated to be
      independent prognostic factors for overall survival and progression-free
      survival. Besides, in wild-type group, patients treated with chemotherapy plus
      targeted therapy exhibited the most favorable prognosis. Therefore, RAS/BRAF
      mutations may serve as indicators for prognosis and treatment options in mCRC.

PMID- 29643918
TI  - Prognostic Value of Combination of Pretreatment Red Cell Distribution Width and
      Neutrophil-to-Lymphocyte Ratio in Patients with Gastric Cancer.
AB  - Aims: Gastric cancer (GC) is often diagnosed at an advanced stage; inexpensive
      and valid biomarkers for GC are still unavailable. We aimed to evaluate the
      prognosis of the combination of pretreatment red cell distribution width (RDW)
      and neutrophil-to-lymphocyte ratio (NLR) in patients with GC. Methods: A
      retrospective analysis from 103 GC patients who were diagnosed at our institution
      from 2012 to 2016 was performed. Both pretreatment RDW and NLR were calculated
      based on the recommended cutoff values of 13.4% and 2.755, respectively. Combined
      values of RDW and NLR (RDW + NLR) stratified patients into a score of 0 (RDW <=
      13.4% and NLR <= 2.755), a score of 1 (RDW > 13.4% or NLR > 2.755), and a score
      of 2 (RDW > 13.4% and NLR > 2.755). Prognostic significances for overall survival
      (OS) and progression-free survival (PFS) were assessed. Results: Pretreatment RDW
      + NLR was a significantly independent prognostic factor for OS and PFS. Moreover,
      high RDW + NLR was strongly related to age, tumor location, TNM stage, CA125, and
      CA199. In a subgroup analysis for patients with advanced gastric cancer (AGC), we
      observed that the level of RDW + NLR was markedly associated with OS and PFS.
      Conclusion: Pretreatment RDW + NLR is a simple, inexpensive, and valid prognostic
      system to predict the survival in patients with GC, especially AGC.

PMID- 29643920
TI  - miR-33 inhibition attenuates the effect of liver X receptor agonist T0901317 on
      expression of liver X receptor alpha in mice liver.
AB  - BACKGROUND: microRNAs play pivotal roles in metabolism and other aspects of cell
      biology. microRNA-33 and liver X receptor (LXR) affect lipid metabolism and
      cholesterol trafficking. In this study, we evaluated effects of co-administration
      of miR-33 inhibitor and LXR activator on LXR-alpha and adenosine triphosphate
      binding cassette transporter A1 (ABCA1) expression in mice liver. METHODS: Twenty
      four mice were randomly allocated into four groups (n = 6). Group 1 mice received
      standard chow diet without any treatment, group 2 received 30 mg/kg/48 hour LXR
      agonist (T0901317), group 3 received 1 mg/kg/48 hour in vivo locked nucleic acids
      (LNA) anti-miR-33 and group 4 received both T0901317 and in vivo LNA anti-miR-33.
      All treatments were administrated through intraperitoneal injection (IP). After 7
      days and at the end of the study, mice were sacrificed, liver tissues were
      excised and blood samples were collected. LXR-alpha and ABCA1 genes and protein
      expression were quantified by real-time polymerase chain reaction (PCR) and
      western blotting, respectively. RESULTS: LXR activation caused LXR-alpha and
      ABCA1 mRNA (P < 0.050) and protein elevation as compared to control (P < 0.001).
      miR-33 inhibition attenuates T0901317 effect on LXR-alpha expression in group IV.
      Co-administration of T0901317 and anti-miR-33 remarkably elevated high-density
      lipoprotein cholesterol (HDL-C) levels, compared to control group (P = 0.001).
      Separate administration of T0901317 and anti-miR-33 also elevated HDL-C levels (P
      < 0.010). CONCLUSION: Co-administration of T0901317 and anti-miR-33 can be
      considered as a good therapeutic alternative for atherosclerosis because miR-33
      inhibition reduced lipogenic effects of LXR-alpha activator and also helps LXR
      alpha agonist to increase reverse cholesterol transport (RCT) and also HDL-C as
      antiatherogenic effects.

PMID- 29643919
TI  - An update on molecular cat allergens: Fel d 1 and what else? Chapter 1: Fel d 1,
      the major cat allergen.
AB  - Background: Cats are the major source of indoor inhalant allergens after house
      dust mites. The global incidence of cat allergies is rising sharply, posing a
      major public health problem. Ten cat allergens have been identified. The major
      allergen responsible for symptoms is Fel d 1, a secretoglobin and not a
      lipocalin, making the cat a special case among mammals. Main body: Given its
      clinical predominance, it is essential to have a good knowledge of this
      allergenic fraction, including its basic structure, to understand the new
      exciting diagnostic and therapeutic applications currently in development. The
      recent arrival of the component-resolved diagnosis, which uses molecular
      allergens, represents a unique opportunity to improve our understanding of the
      disease. Recombinant Fel d 1 is now available for in vitro diagnosis by the anti
      Fel d 1 specific IgE assay. The first part of the review will seek to describe
      the recent advances related to Fel d 1 in terms of positive diagnosis and
      assessment of disease severity. In daily practice, anti-Fel d 1 IgE tend to
      replace those directed against the overall extract but is this attitude
      justified? We will look at the most recent arguments to try to answer this
      question. In parallel, a second revolution is taking place thanks to molecular
      engineering, which has allowed the development of various forms of recombinant
      Fel d 1 and which seeks to modify the immunomodulatory properties of the molecule
      and thus the clinical history of the disease via various modalities of anti-Fel d
      1-specific immunotherapy. We will endeavor to give a clear and practical overview
      of all these trends.

PMID- 29643921
TI  - Air pollution and cardiovascular and respiratory disease: Rationale and
      methodology of CAPACITY study.
AB  - BACKGROUND: Considering the high level of air pollution and its impact on health,
      we aimed to study the correlation of air pollution with hospitalization and
      mortality of cardiovascular (CVD) and respiratory diseases (ResD) (CAPACITY) to
      determine the effects of air pollutants on CVD and ResD hospitalizations and
      deaths in Isfahan, Iran. METHODS: Hourly levels of air pollutants including
      particulate matter (PM), carbon monoxide (CO), nitrogen dioxide (NO2), sulfur
      dioxide (SO2), and ozone (O3), information of CVD and ResD admissions and death
      certificate were obtained respectively from Department of Environment (DOE),
      Iran, hospitals and cemetery. Time series and case-crossover model were used to
      find the impact of air pollutants. This paper only summarizes the descriptive
      findings of the CAPACITY study. RESULTS: The total number of hospitalized
      patients were 23781 in 2010 and 22485 in 2011. The most frequent cause of
      hospitalization and death was ischemic heart diseases in both years. While the
      mean annual levels of O3, CO, and PM10 were lower in 2011 than in 2010, NO2 and
      SO2 levels higher in 2011. In both years, PM10 was similarly increased during
      last month of fall, late spring and early summer. In 2011, the PM2.5 and PM10
      monthly trend of change were similar. CONCLUSION: The CAPACITY study is one of
      the few large-scale studies that evaluated the effects of air pollutants on a
      variety of CVD and ResD in a large city of Iran. This study can provide many
      findings that could clarify the effects of these pollutants on the incidence and
      burden of both disease groups.

PMID- 29643922
TI  - An investigation of the psychological experiences of patients under mechanical
      ventilation following open heart surgery.
AB  - BACKGROUND: Breathing and living on mechanical ventilation develops a different
      feeling in patients. Most of such feelings and experiences are not pleasant and
      can lead to psychiatric disorders in the patients after they are detached from
      the ventilator. The aim of this study is to explore the psychological experiences
      of patients under mechanical ventilation. METHODS: This qualitative study was
      conducted according to an interpretive epistemological approach in 2016. Fifteen
      participants were selected according to purposive sampling. Data were drawn from
      the transcripts of in-depth, semi-structured interview that were not discontinued
      until data saturation was ensured. The participants were asked to share what they
      experienced when they were under mechanical ventilation and intubation. Data
      analysis was conducted according to Diekelmann method. RESULTS: Altogether, 2
      themes, 7 subthemes, and 27 sub-subthemes were drawn from the data. Two themes
      were dread (a horrible experience) and hope (an inspiring experience). Dread
      consisted of anxiety, hopelessness, and dependency. Hope consisted of spiritual
      connection as the only possible effort, the presence of health team the source of
      comfort, the family looking forward, and overcoming the illness (a step to life).
      CONCLUSION: The psychological experiences of patients under mechanical
      ventilation are specific, and nurses can play an important role in decreasing
      tension and increasing hope among them through gaining knowledge about their
      experiences.

PMID- 29643923
TI  - The effect of atorvastatin treatment duration on oxidative stress markers and
      lipid profile in patients with coronary artery diseases: A case series study.
AB  - BACKGROUND: The major aim of this study was evaluating the effect of atorvastatin
      treatment on thiobarbituric acid reactive substances (TBARS), ferric reducing the
      ability of plasma (FRAP), small dense low-density lipoprotein cholesterol (sdLDL)
      and lipid profile in coronary artery disease (CAD) patients. METHODS: This study
      was carried out on 83 patients with angiographically proven coronary artery
      stenosis (52 men and 31 women) at Shahid Madani Hospital, Khorramabad, Iran, in
      2015. The patients were divided into the 3 groups. 27 patients were classified
      statins consumption less than 6 days, 28 patients for 6 to 90 days, and 28
      patients for more than 90 days. The level of sdLDL, lipid profile, TBARS and FRAP
      were assayed. RESULTS: FRAP levels of patients that received atorvastatin for
      more than 90 days (832 +/- 101) were significantly elevated (P = 0.01) compared
      to the patients received atorvastatin less than 6 days (688 +/- 75), whereas the
      levels of TBARS diminished significantly (P = 0.04). Also, the levels of total
      cholesterol (TC) and LDL-C were significantly decreased after 3 months of
      atorvastatin receiving (158 as compared to patients that consumed atorvastatin
      less than 6 days), (P = 0.02 and 0.03, respectively). The level of sdLDL was
      slightly increased with long-time consumption of atorvastatin (37 +/- 14) in
      patients in comparison with patients that received atorvastatin less than 6 days
      (32 +/- 15) (P = 0.06), but was not significant. CONCLUSION: The serum level of
      TBARS decreased and the serum level of FRAP increased in patients with long-time
      receiving atorvastatin. Therefore, atorvastatin contributes to the lowering
      oxidative stress in these patients.

PMID- 29643924
TI  - The relationship between shift work and Framingham risk score: A five-year
      prospective cohort study.
AB  - BACKGROUND: There is a small number of studies that considered the relationship
      between shift work (SW) and Framingham risk score (FRS). This study prospectively
      examined the association between SW and FRS among man workers based on the
      multilevel modeling approach. METHODS: This five-year prospective cohort study
      was done among workers (using stratified random sampling) who work in Esfahan's
      Mobarakeh Steel Company (EMSC), Iran, from March 2011 to February 2015. RESULTS:
      The study sample included 1626 man workers (mean age = 40.0 +/- 6.2). Among these
      subjects, 652 (40.01%), 183 (11.3%) and 791 (48.6%) were day workers, weekly
      rotating shift workers and routinely rotating, respectively. After controlling
      unbalanced variables, there was no any significant association between SW and
      FRS. CONCLUSION: The results of this prospective cohort study did not show a
      relationship between SW and FRS.

PMID- 29643925
TI  - Isolated double-orifice mitral valve in a young girl.
AB  - BACKGROUND: Double-orifice mitral valve (DOMV) is an extremely rare cardiac
      malformation. It has been found to be accompanied by congenital anomalies (CAs),
      however, it can be detected as an isolated anomaly. The clinical findings of a
      DOMV are variable and depend predominantly on the associated cardiac
      abnormalities, particularly atrioventricular septal defects or mitral valve (MV)
      regurgitation and/or stenosis. CASE REPORT: In this regard, we describe an
      isolated DOMV in an 18-year-old young girl who complained of a short-term
      nonspecific chest pain. She underwent transthoracic and transesophageal
      echocardiographic examinations. The examinations revealed a DOMV without any
      valvular or structural malformations. Other examinations were unremarkable. The
      patient did need neither medical nor surgical interventions. CONCLUSION: The
      isolated cases of DOMV do not need therapy and might be only followed up using
      echocardiographic examinations. However, a careful echocardiographic examination
      for detection of concomitant structural malformations would be of great
      importance in the management of such cases.

PMID- 29643926
TI  - The evaluation of left ventricular diastolic dysfunction in patients with non
      hemorrhagic stroke and atrial fibrillation.
AB  - BACKGROUND: Atrial fibrillation (AF) is the most common tachyarrhythmia and an
      important risk factor for thromboembolic stroke. CHA2DS2-VASc score was
      introduced for assessment of embolic events and as criteria for starting
      anticoagulants. This study was performed to evaluate the left ventricular
      diastolic dysfunction (LVDD) in patients with non-hemorrhagic stroke and AF.
      METHODS: This cross-sectional study consisted of 76 consecutive patients with
      suspected non-hemorrhagic stroke referred to the Cardiology Department of Alzahra
      and Ayatollah Kashani hospitals in Isfahan, Iran, during 2015-2016. Demographic,
      anthropometric and clinical characteristics were evaluated for all patients at
      baseline. CHA2DS2-VASc score was calculated for all. All eligible patients
      underwent transthoracic echocardiogram (TTE) and LVDD was measured in the
      patients. RESULTS: The mean age of the patients was 64.64 +/- 5.95 years and 28
      subjects (36.8%) were women. The most common underlying disease in the patients
      was hypertension (HTN) (65.8%). Median (range) CHA2DS2-VASc score was 4 (1-7).
      Four patients (5.3%) had paroxysmal AF and 16 cases (21.1%) had LVDD. Analysis
      showed that LVDD in patients with non-hemorrhagic stroke and coexisting AF was
      not associated with CHA2DS2-VASc score (r = 0.151, P = 0.192). CONCLUSION: LVDD
      is not associated with CHA2DS2-VASc score in patients with non-hemorrhagic stroke
      and coexisting AF.

PMID- 29643927
TI  - Mouse Models of beta-cell KATP Channel Dysfunction.
AB  - ATP-sensitive K+ (KATP) channels in pancreatic beta-cells couple glucose
      metabolism to insulin secretion. Reduced KATP channel activity produces excessive
      insulin release and hyperinsulinism whereas increased KATP channel activity leads
      to lower insulin secretion and diabetes. Paradoxically, mice with genetic
      deletion of KATP channels, or loss-of-function mutations, are only transiently
      hypoglycaemic during the neonatal period and often display reduced glucose
      stimulated insulin secretion subsequently. Mice with KATP channel gain-of
      function mutations are hyperglycaemic and have impaired glucose-stimulated
      insulin secretion, a phenotype that accurately mimics human diabetes. This review
      discusses how mice expressing altered KATP channels have provided valuable
      insight into beta-cell function.

PMID- 29643928
TI  - Effect of low energy diet for eight weeks to adults with overweight or obesity on
      folate, retinol, vitamin B12, D and E status and the degree of inflammation: a
      post hoc analysis of a randomized intervention trial.
AB  - Background: Obesity is associated with vitamin insufficiency and low grade
      inflammation. The purpose of this study was to investigate the effect of weight
      loss on folate, retinol, vitamin B12, D and E status and the degree of
      inflammation. Methods: Out of 110, 85 individuals (75% women) aged 39 +/- 11
      years with a mean +/- SD BMI of 33 +/- 4 kg/m2, completed an eight-week low
      energy diet (LED). Serum concentration of folate, retinol, B12, D and E and C
      reactive protein and homocysteine (Hcy) were measured at baseline and at end of
      the LED. Results: At baseline, 8% of the participants were deficient in folate,
      13% in vitamin B12, 2% in retinol, 28% in vitamin D (72% were insufficient in
      vitamin D), and none were deficient in vitamin E. At baseline, BMI was inversely
      associated with retinol (P < 0.05) as was total and abdominal fat percentage with
      folate (P < 0.05); further BMI and measures of adiposity were positively
      associated with CRP (P < 0.01) and Hcy (P < 0.05). Homocysteine was inversely
      associated with all vitamins but retinol (P < 0.001). After the LED, the
      participants lost a mean [95% confidence intervals] of 12.3 [- 13.1,-11.6] kg.
      The serum concentration of folate, vitamin B12 and D were increased (P < 0.001)
      after the LED whereas the concentration of retinol and vitamin E were reduced (P
      < 0.001). Conclusion: Eight-weeks LED resulted in 13% weight loss and an increase
      in the serum concentrations of folate, vitamin B12 and D. Baseline adiposity was
      inversely associated with folate and retinol, and positively associated with
      markers of inflammation. Trial registration: Ethical Committee of Copenhagen as
      no. H-4-2013-135, NCT01561131.

PMID- 29643929
TI  - Colorectal Cancer Screening: The Role of Psychological, Social and Background
      Factors in Decision-making Process.
AB  - Since ColoRectal Cancer (CRC) remains the third cause of cancer death in the
      world, a better understanding of the reasons underlying poor adherence to and
      delay in undergoing CRC screening programs is important. CRC screening decision
      making process can be conceptualized as the relationship between intention and
      behavior and needs to be investigated including the impact on patients' decision
      of a broad range of psychological factors and personal predisposition as fear of
      a positive screening test, poor understanding of the procedure, psychological
      distress, anxiety, anticipation of pain, feelings of embarrassment and
      vulnerability. Also socioeconomic, ethnic and sociological influences, and
      organizational barriers have been identified as factors influencing CRC screening
      adherence. Decision-making process can finally be influenced by the healthcare
      background in which the intervention is promoted and screening programs are
      carried out. However, there is still a gap on the scientific knowledge about the
      influences of diverse elements on screening adherence and this deserves further
      investigations in order to carry out more focused and effective prevention
      programs.

PMID- 29643930
TI  - The Physical Body Experiences Questionnaire Simplified for Active Aging (PBE
      QAG).
AB  - Background: The physical activity has been indicated as an experience that can
      help achieve positive, self-oriented own body awareness. This awareness is an
      aspect that tends to get worse with age. Objective: Our study aims to verify the
      internal consistency of a questionnaire on physical awareness in a sample of
      Italian elders; a secondary objective is to measure if there is a relationship
      between physical awareness and perceived level of physical activity. Methods:
      Cross sectional study on a consecutive sample of elderly people was administered
      the "Physical Body Experiences Questionnaire simplified for active aging (PBE
      QAG)", inspired by the "Physical Body Experiences Questionnaire", modified,
      simplified and adapted to be used in the elderly over 65. To elderly people the
      International Physical Activity Questionnaire. Cronbach's alpha was also used to
      assess internal reliability of the total PBE-QAG. The factor structure was
      evaluated through Confirmatory Factor Analyses (CFAs). Results: The Cronbach's
      alpha was 0.8 for the "body-mind relationship" scale, 0.81 for the "accepting
      your body" scale, 0.83 for the "awareness of physical skills" scale, and 0.65 for
      the "awareness of physical limits" scale. Cronbach's alpha for the total PBE-QAG
      was 0.89. The CFA indicated a model with the 4 factors (CFI = 0.989, TLI = 0.984,
      RMSEA = 0.076).People who conducted physical activity assiduously or regularly
      and over 10 minutes showed a better score to the PBE-QAG than those who declared
      a sporadic activity and for "less than 10 minute", respectively. Conclusion: Our
      study revealed that the PBE-QAG shows an excellent total internal consistency. In
      the Italian sample of elderly people the questionnaire shows the model with the 4
      factors described in literature.

PMID- 29643931
TI  - Remission in Depression and Associated Factors at Different Assessment Times in
      Primary Care in Chile.
AB  - Objective: To determine the factors associated with remission at 3, 6, 9 and 12
      months among depressive adult patients in primary care [PHC] in Chile. Methods:
      This is a one-year naturalistic study that followed 297 patients admitted for
      treatment of depression in eight primary care clinics in Chile. Initially,
      patients were evaluated using: the International Mini-Neuropsychiatric Interview
      [MINI], a screening for Childhood Trauma Events [CTEs], the Life Experiences
      Survey and a partner violence scale. The Hamilton Depression Scale [HDRS] was
      used to follow the patients during the observation time. Associations between the
      factors studied and the primary outcome remission [HDRS <= 7] were assessed using
      a dichotomous logistic regression and a multivariate Poisson regression. The
      significance level was 0.05. Results: Remission [HDRS <= 7] ranged between 36.7%
      at 3 months and 53.9% at 12 months. Factors that predicted poor remission during
      the observation time were: CTEs [Wald X2 = 4.88, Exp B=0.94, CI 0.90-0.92,
      p=0.27]; psychiatric comorbidities [Wald X2 = 10.73, Exp B=0.90, CI 0.85-0.96,
      p=0.01]; suicidal tendencies [Wald X2 = 4.66, Exp B=0.88, CI 0.79-0.98, p=0.03]
      and prior treatment for depression [Wald X2 = 4.50, Exp B=0.81, CI 0.68-0.85,
      p=0.03]. Discussion: Almost 50% of this sample failed remission in depression at
      12 months. Psychiatric comorbidities and CTEs are factors that should be
      considered for a poor outcome in depressed Chilean patients. These factors need
      more recognition and a better approach in PHC.

PMID- 29643932
TI  - Effect of maternal country of birth on breastfeeding practices: results from
      Portuguese GXXI birth cohort.
AB  - Background: Maternal country of birth has been associated with perinatal health
      outcomes but less is known regarding breastfeeding practices in contemporary
      European settings. This study investigated effect of maternal country of birth on
      breastfeeding initiation and duration by comparing native Portuguese and migrant
      mothers. Methods: We analyzed data of 7065 children of the Generation XXI (GXXI)
      birth cohort recruited at birth (2005-06) and followed-up 4 years later. Logistic
      regression was used to assess the effect of maternal country of birth on
      breastfeeding initiation. Kaplan-Meier estimate was used to compare breastfeeding
      duration by maternal country of birth and length of residence by migrant mothers
      in Portugal. Results: Breastfeeding initiation and the type of breastfeeding
      practice were similar for native Portuguese and migrant mothers. The migrants had
      significantly higher median duration in months of any breastfeeding (Odds Ratio
      [OR] 6.0, 95% Confidence Interval [CI] 5.4,6.6) and exclusive breastfeeding (OR
      4.0, 95% CI 3.8,4.2) than native Portuguese mothers (OR 4.0, 95% CI 3.8,4.2 and
      OR 3.0, 95% CI 2.9,3.0). Migrant mothers who resided in Portugal for either <=5
      years (OR 5.0, 95% CI 3.9,6.1 and OR 4.0, 95% CI 3.8,4.2) or >  5 years (OR 6.0,
      95% CI 5.5,6.5 and OR 4.0, 95% CI 3.7,4.3) years had similar duration of any
      breastfeeding or exclusive breastfeeding, in both cases higher than the native
      Portuguese mothers. No significant differences were found when world regions were
      compared. Conclusions: Maternal country of birth does not influence breastfeeding
      initiation and type of feeding practice. However, migrant mothers have longer
      breastfeeding duration of either exclusive or any breastfeeding, which was not
      changed by length of residence in Portugal.

PMID- 29643935
TI  - Changes in fatigue, autonomic functions, and blood biomarkers due to sitting
      isometric yoga in patients with chronic fatigue syndrome.
AB  - Background: In a previous randomized controlled trial, we found that sitting
      isometric yoga improves fatigue in patients with chronic fatigue syndrome (CFS)
      who are resistant to conventional therapy. The aim of this study was to
      investigate possible mechanisms behind this finding, focusing on the short-term
      fatigue-relieving effect, by comparing autonomic nervous function and blood
      biomarkers before and after a session of isometric yoga. Methods: Fifteen
      patients with CFS who remained symptomatic despite at least 6 months of
      conventional therapy practiced sitting isometric yoga (biweekly 20 min practice
      with a yoga instructor and daily home practice) for eight weeks. Acute effects of
      sitting isometric yoga on fatigue, autonomic function, and blood biomarkers were
      investigated after the final session with an instructor. The effect of a single
      session of sitting isometric yoga on fatigue was assessed by the Profile of Mood
      Status (POMS) questionnaire immediately before and after the session. Autonomic
      nervous function (heart rate (HR) variability) and blood biomarkers (cortisol,
      DHEA-S, TNF-alpha, IL-6, IFN-gamma, IFN-alpha, prolactin, carnitine, TGF-beta1,
      BDNF, MHPG, and HVA) were compared before and after the session. Results: Sitting
      isometric yoga significantly reduced the POMS fatigue score (p < 0.01) and
      increased the vigor score (p < 0.01). It also reduced HR (p < 0.05) and increased
      the high frequency power (p < 0.05) of HR variability. Sitting isometric yoga
      increased serum levels of DHEA-S (p < 0.05), reduced levels of cortisol (p <
      0.05) and TNF-alpha (p < 0.05), and had a tendency to reduce serum levels of
      prolactin (p < 0.1). Decreases in fatigue scores correlated with changes in
      plasma levels of TGF-beta1 and BDNF. In contrast, increased vigor positively
      correlated with HVA. Conclusions: A single session of sitting isometric yoga
      reduced fatigue and increased vigor in patients with CFS. Yoga also increased
      vagal nerve function and changed blood biomarkers in a pattern that suggested
      anti-stress and anti-inflammatory effects. These changes appear to be related to
      the short-term fatigue-relieving effect of sitting isometric yoga in patients
      with CFS. Furthermore, dopaminergic nervous system activation might account for
      sitting isometric yoga-induced increases in energy in this patient population.
      Trial registration: University Hospital Medical Information Network (UMIN CTR)
      UMIN000009646. Registered Dec 27, 2012.

PMID- 29643933
TI  - Human papillomavirus genome variants and head and neck cancers: a perspective.
AB  - Human papillomaviruses (HPV) cause infections that are responsible for diverse
      clinical manifestations from benign conditions to invasive cancer. As different
      HPV types are associated with variable pathogenic potential, minor genetic
      variations within a given high-risk HPV type might also be associated with
      distinct oncogenic capacities, through variable ability of persistence or risk of
      progression to precancer/cancer. Most recent HPV variant studies in the cervix
      using latest sequencing technology confirmed that minor changes in the HPV genome
      can have a major influence on carcinogenesis and have revealed key data that help
      better understand the carcinogenicity of HPV at a molecular level. Here we review
      the limited number of studies on HPV genome variants in head and neck cancers
      (HNC) and discuss their implications for cancer research in the light of
      accumulated knowledge for the cervix. Challenges in transposing HPV variant
      studies from the lower anogenital to the upper aerodigestive tract are also
      discussed, highlighting the main gaps of knowledge in the field of HPV-induced
      HNC. Specifically in the head and neck region, the lack of characterisation of
      precancerous lesions and the difficulty in sampling normal tissue will challenge
      the development of accurate studies. Although there is so far no indication that
      HPV variant research in HNC could directly translate into clinical application,
      such research is expected to be useful to disentangle unanswered questions in the
      pathogenesis of HNC. Yet, history of HPV variant research suggests that, to be
      successful, studies will require large international collaborative efforts.

PMID- 29643934
TI  - Extra-telomeric functions of telomerase in the pathogenesis of Epstein-Barr virus
      driven B-cell malignancies and potential therapeutic implications.
AB  - The Epstein-Barr virus (EBV) is a ubiquitous human gamma-herpesvirus causally
      linked to a broad spectrum of both lymphoid and epithelial malignancies. In order
      to maintain its persistence in host cells and promote tumorigenesis, EBV must
      restrict its lytic cycle, which would ultimately lead to cell death, selectively
      express latent viral proteins, and establish an unlimited proliferative
      potential. The latter step depends on the maintenance of telomere length provided
      by telomerase. The viral oncoprotein LMP-1 activates TERT, the catalytic
      component of telomerase. In addition to its canonical role in stabilizing
      telomeres, TERT may promote EBV-driven tumorigenesis through extra-telomeric
      functions. TERT contributes toward preserving EBV latency; in fact, through the
      NOTCH2/BATF pathway, TERT negatively affects the expression of BZLF1, the master
      regulator of the EBV lytic cycle. In contrast, TERT inhibition triggers a
      complete EBV lytic cycle, leading to the death of EBV-infected cells.
      Interestingly, short-term TERT inhibition causes cell cycle arrest and apoptosis,
      partly by inducing telomere-independent activation of the ATM/ATR/TP53 pathway.
      Importantly, TERT inhibition also sensitizes EBV-positive tumor cells to
      antiviral therapy and enhances the pro-apoptotic effects of chemotherapeutic
      agents. We provide here an overview on how the extra-telomeric functions of TERT
      contribute to EBV-driven tumorigenesis. We also discuss the potential therapeutic
      approach of TERT inhibition in EBV-driven malignancies.

PMID- 29643936
TI  - Single cell assessment of yeast metabolic engineering for enhanced lipid
      production using Raman and AFM-IR imaging.
AB  - Background: Biodiesel is a valuable renewable fuel made from derivatized fatty
      acids produced in plants, animals, and oleaginous microbes. Of the latter, yeasts
      are of special interest due to their wide use in biotechnology, ability to
      synthesize fatty acids and store large amounts of triacylglycerols while
      utilizing non-food carbon sources. While yeast efficiently produce lipids,
      genetic modification and indeed, lipid pathway metabolic engineering, is usually
      required for cost-effective production. Traditionally, gas chromatography (GC) is
      used to measure fatty acid production and to track the success of a metabolic
      engineering strategy in a microbial culture; here we have employed vibrational
      spectroscopy approaches at population and single cell level of engineered yeast
      while simultaneously investigating metabolite levels in subcellular structures.
      Results: Firstly, a strong correlation (r2 > 0.99) was established between
      Fourier transform infrared (FTIR) lipid in intact cells and GC analysis of fatty
      acid methyl esters in the differently engineered strains. Confocal Raman
      spectroscopy of individual cells carrying genetic modifications to enhance fatty
      acid synthesis and lipid accumulation revealed changes to the lipid body (LB),
      the storage organelle for lipids in yeast, with their number increasing markedly
      (up to tenfold higher); LB size was almost double in the strain that also
      expressed a LB stabilizing gene but considerable variation was also noted between
      cells. Raman spectroscopy revealed a clear trend toward reduced unsaturated fatty
      acid content in lipids of cells carrying more complex metabolic engineering.
      Atomic force microscopy-infrared spectroscopy (AFM-IR) analysis of individual
      cells indicated large differences in subcellular constituents between strains:
      cells of the most highly engineered strain had elevated lipid and much reduced
      carbohydrate in their cytoplasm compared with unmodified cells. Conclusions:
      Vibrational spectroscopy analysis allowed the simultaneous measurement of strain
      variability in metabolite production and impact on cellular structures as a
      result of different gene introductions or knockouts, within a lipid metabolic
      engineering strategy and these inform the next steps in comprehensive lipid
      engineering. Additionally, single cell spectroscopic analysis measures
      heterogeneity in metabolite production across microbial cultures under genetic
      modification, an emerging issue for efficient biotechnological production.

PMID- 29643937
TI  - Endogenous lycopene improves ethanol production under acetic acid stress in
      Saccharomyces cerevisiae.
AB  - Background: Acetic acid, generated from the pretreatment of lignocellulosic
      biomass, is a significant obstacle for lignocellulosic ethanol production.
      Reactive oxidative species (ROS)-mediated cell damage is one of important issues
      caused by acetic acid. It has been reported that decreasing ROS level can improve
      the acetic acid tolerance of Saccharomyces cerevisiae. Results: Lycopene is known
      as an antioxidant. In the study, we investigated effects of endogenous lycopene
      on cell growth and ethanol production of S. cerevisiae in acetic acid media. By
      accumulating endogenous lycopene during the aerobic fermentation of the seed
      stage, the intracellular ROS level of strain decreased to 1.4% of that of the
      control strain during ethanol fermentation. In the ethanol fermentation system
      containing 100 g/L glucose and 5.5 g/L acetic acid, the lag phase of strain was
      24 h shorter than that of control strain. Glucose consumption rate and ethanol
      titer of yPS002 got to 2.08 g/L/h and 44.25 g/L, respectively, which were 2.6-
      and 1.3-fold of the control strain. Transcriptional changes of INO1 gene and CTT1
      gene confirmed that endogenous lycopene can decrease oxidative stress and improve
      intracellular environment. Conclusions: Biosynthesis of endogenous lycopene is
      first associated with enhancing tolerance to acetic acid in S. cerevisiae. We
      demonstrate that endogenous lycopene can decrease intracellular ROS level caused
      by acetic acid, thus increasing cell growth and ethanol production. This work
      innovatively   puts forward a new strategy for second generation bioethanol
      production during lignocellulosic fermentation.

PMID- 29643938
TI  - A hybrid reference-guided de novo assembly approach for generating Cyclospora
      mitochondrion genomes.
AB  - Cyclospora cayetanensis is a coccidian parasite associated with large and complex
      foodborne outbreaks worldwide. Linking samples from cyclosporiasis patients
      during foodborne outbreaks with suspected contaminated food sources, using
      conventional epidemiological methods, has been a persistent challenge. To address
      this issue, development of new methods based on potential genomically-derived
      markers for strain-level identification has been a priority for the food safety
      research community. The absence of reference genomes to identify nucleotide and
      structural variants with a high degree of confidence has limited the application
      of using sequencing data for source tracking during outbreak investigations. In
      this work, we determined the quality of a high resolution, curated, public
      mitochondrial genome assembly to be used as a reference genome by applying
      bioinformatic analyses. Using this reference genome, three new mitochondrial
      genome assemblies were built starting with metagenomic reads generated by
      sequencing DNA extracted from oocysts present in stool samples from
      cyclosporiasis patients. Nucleotide variants were identified in the new and other
      publicly available genomes in comparison with the mitochondrial reference genome.
      A consolidated workflow, presented here, to generate new mitochondrion genomes
      using our reference-guided de novo assembly approach could be useful in
      facilitating the generation of other mitochondrion sequences, and in their
      application for subtyping C. cayetanensis strains during foodborne outbreak
      investigations.

PMID- 29643940
TI  - The impact of a disease management programme for type 2 diabetes on health
      related quality of life: multilevel analysis of a cluster-randomised controlled
      trial.
AB  - Background: Type 2 diabetes is a chronic disease associated with poorer health
      outcomes and decreased health related quality of life (HRQoL). The aim of this
      analysis was to explore the impact of a disease management programme (DMP) in
      type 2 diabetes on HRQoL. A multilevel model was used to explain the variation in
      EQ-VAS. Methods: A cluster-randomized controlled trial-analysis of the secondary
      endpoint HRQoL. Our study population were general practitioners and patients in
      the province of Salzburg. The DMP "Therapie-Aktiv" was implemented in the
      intervention group, and controls received usual care. Outcome measure was a
      change in EQ-VAS after 12 months. For comparison of rates, we used Fisher's Exact
      test; for continuous variables the independent T test or Welch test were used. In
      the multilevel modeling, we examined various models, continuously adding
      variables to explain the variation in the dependent variable, starting with an
      empty model, including only the random intercept. We analysed random effects
      parameters in order to disentangle variation of the final EQ-VAS. Results: The EQ
      VAS significantly increased within the intervention group (mean difference 2.19,
      p = 0.005). There was no significant difference in EQ-VAS between groups (mean
      difference 1.00, p = 0.339). In the intervention group the improvement was more
      distinct in women (2.46, p = 0.036) compared to men (1.92, p = 0.063). In
      multilevel modeling, sex, age, family and work circumstances, any macrovascular
      diabetic complication, duration of diabetes, baseline body mass index and
      baseline EQ-VAS significantly influence final EQ-VAS, while DMP does not. The
      final model explains 28.9% (EQ-VAS) of the total variance. Most of the
      unexplained variance was found on patient-level (95%) and less on GP-level (5%).
      Conclusion: DMP "Therapie-Aktiv" has no significant impact on final EQ-VAS. The
      impact of DMPs in type 2 diabetes on HRQoL is still unclear and future programmes
      should focus on patient specific needs and predictors in order to improve
      HRQoL.Trial registration Current Controlled trials Ltd., ISRCTN27414162.

PMID- 29643941
TI  - Demographic and migration-related risk factors for low-level smoking in a farm
      working sample of Latinos (the MICASA study).
AB  - Cigarette smoking is the most preventable cause of death in the U.S. Research
      regarding the phenomenon of low-level smoking, defined as smoking one to five
      cigarettes per day (CPD) on average, is increasing as its high prevalence is
      better recognized. The Mexican Immigration to California: Agricultural Safety and
      Acculturation (MICASA) study is a prospective cohort study of Latino hired farm
      worker families that assesses respiratory health, including patterns and
      behaviors of cigarette smoking. The purpose of the present analysis was to
      establish demographic, migration-related, and psychosocial characteristics and
      risk factors for low-level smoking. Seven percent of participants were current
      smokers, 61% of them being low-level smokers. Low-level smokers did not smoke as
      many days during the past month as those who smoke 6+ CPD (p=0.04). Low-level
      smokers were more likely than never and former smokers combined not to be married
      and to experience frequent mental distress. Those who smoke 6+ CPD were also more
      likely than never and former smokers combined to experience frequent mental
      distress and to be more acculturated. Low-level smokers have characteristics and
      risk factors that set them apart from other types of smokers. This increased
      understanding of low-level smokers can enhance public health education and
      smoking cessation programs targeted at Latinos.

PMID- 29643942
TI  - Congregational Composition and Explanations for Racial Inequality Among Black
      Religious Affiliates.
AB  - Objective: Prior research suggests that congregational characteristics are
      associated with the racial attitudes of Black churchgoers. This study examines
      the relationship between congregational diversity and beliefs about the
      Black/White socioeconomic gap among Black religious adherents. Method: Drawing
      upon pooled data from the General Social Survey and the National Congregations
      Study, we fit binary logistic regression models to estimate the association
      between congregational size and the explanations of Black/White economic
      inequality among Black religious adherents. Results: Findings from our study
      reveal that congregational diversity is one factor that accounts for intragroup
      differences in racial attitudes among Black religious affiliates. Relative to
      Blacks that attend religious services in overwhelmingly Black congregations,
      Blacks that attend religious services in congregations that are overwhelmingly
      White and are overwhelmingly comprised of non-Black racial/ethnic minorities are
      significantly less likely to attribute Black/White socioeconomic gaps to
      structural factors. Conclusion: Our study demonstrates that congregational
      diversity is a source of intragroup variation in racial attitudes among Black
      religious affiliates, which may attenuate the ability of such congregations to
      bridge racial divisions.

PMID- 29643939
TI  - Sphingolipid regulators of cellular dysfunction in Type 2 diabetes mellitus: a
      systems overview.
AB  - Climbing obesity rates have contributed to worldwide increases in obesity
      associated diseases, including the metabolic syndrome and Type 2 diabetes
      mellitus (T2DM). Sphingolipids, an important class of structural and signaling
      lipids, have emerged as key players in the development and pathogenesis of
      insulin resistance and T2DM. More specifically, sphingolipids have been
      demonstrated to play integral roles in lipotoxicity and other aspects of
      pathogenesis in T2DM, although the cellular mechanisms by which this occurs and
      by which sphingolipid metabolism is dysregulated in T2DM remain under
      investigation. This review summarizes current knowledge of sphingolipid
      metabolism and signaling in key organs and tissues affected by T2DM, including
      the pancreas, adipose tissue, skeletal muscle, cardiovascular system and liver,
      and highlights areas that ripe for future investigation.

PMID- 29643943
TI  - H19 overexpression promotes leukemogenesis and predicts unfavorable prognosis in
      acute myeloid leukemia.
AB  - Background: The long non-coding RNA H19 plays a crucial role in solid tumor
      initiation and progression. However, the potential role of H19 and its clinical
      significance in acute myeloid leukemia (AML) remain largely elusive. Methods: H19
      expression was detected by qPCR, and clinical significance in AML patients was
      further analyzed. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus
      (GEO) data for AML were used as validation cohorts. The roles of H19 in cell
      proliferation and apoptosis were determined by cell proliferation assay and flow
      cytometry analysis. Results: H19 expression was significantly increased in AML
      patients but not associated with embedded miR-675 expression. Moreover, H19
      overexpression was not dependent on the methylation pattern in H19 differentially
      methylated region/imprinting control region. Strong association was observed
      between H19 overexpression and patients' characteristics including sex, higher
      white blood cells, older age, and intermediate karyotype, FLT3-ITD, and DNMT3A
      mutations. In addition, H19 overexpression correlated with lower complete
      remission (CR) rate and shorter overall survival, and further confirmed by
      multivariate analyses. Importantly, the prognostic effect of H19 expression was
      validated by TCGA and GEO data. In the follow-up of patients, H19 expression in
      CR phase was lower than diagnosis time and returned at relapse time. Loss-of
      function experiments showed that H19 exhibited anti-proliferative and pro
      apoptotic effects in leukemic cell HL60. Furthermore, H19 expression was
      positively correlated with potential downstream gene ID2 in AML. Conclusions: Our
      findings revealed that methylation-independent H19 was a prognostic and
      predictive biomarker in AML, and H19/ID2 played crucial roles in leukemogenesis
      with potential therapeutic target value.

PMID- 29643944
TI  - Competing endogenous RNA expression profiling in pre-eclampsia identifies
      hsa_circ_0036877 as a potential novel blood biomarker for early pre-eclampsia.
AB  - Background: The etiology and pathogenesis of pre-eclampsia (PE) is unclear, and
      there is no ideal early clinical biomarker for prediction of PE. The competing
      endogenous RNA (ceRNA) hypothesis is a new approach to uncover the molecular
      pathology of PE. The first aim of this study was to perform messenger RNA, long
      non-coding RNA, and circular RNA (circRNA) expression profiling of human normal
      and severe pre-eclampsia (SPE) placentas. circRNA, which has a stable structure,
      is a more suitable biomarker than other types of RNA. Therefore, the second aim
      of our study was to select some differentially expressed circRNAs in PE placentas
      as early clinical biomarkers of PE in blood circulation. Results: Using
      microarray analysis, we investigated differentially expressed ceRNAs in human
      normal and SPE placentas. Bioinformatics, such as gene ontology, KEGG pathway,
      and ceRNA network analyses, were performed to evaluate the microarray data and
      gain further insights into the biological processes. RNAs (Chd5, Furin, lnc
      ELAVL4-9:1, lnc-RAP1GAP2-5:2, hsa_circ_0036877, hsa_circ_0036878,
      hsa_circ_0055724, hsa_circ_0049730, and hsa_circ_0036474) were validated by
      quantitative real-time PCR (qRT-PCR). RNA immunoprecipitation (RIP) of AGO2 in
      htra-8 cells and qRT-PCR analysis of hsa_circ_0036877 expression in maternal
      whole peripheral blood samples of participants were then conducted to confirm
      that hsa_circ_0036877 is a ceRNA and potential novel blood biomarker for early
      PE, respectively. Conclusion: Our study is the first systematic profiling of
      ceRNAs in placentas of PE patients and revealed the global ceRNA network
      integration in PE. Moreover, hsa_circ_0036877 can function as a ceRNA and serve
      as a potential novel blood biomarker for early PE.

PMID- 29643945
TI  - Epigenome-wide association study of metabolic syndrome in African-American
      adults.
AB  - Background: The high prevalence of obesity among US adults has resulted in
      significant increases in associated metabolic disorders such as diabetes,
      dyslipidemia, and high blood pressure. Together, these disorders constitute
      metabolic syndrome, a clinically defined condition highly prevalent among African
      Americans. Identifying epigenetic alterations associated with metabolic syndrome
      may provide additional information regarding etiology beyond current evidence
      from genome-wide association studies. Methods: Data on metabolic syndrome and DNA
      methylation was assessed on 614 African-Americans from the Hypertension Genetic
      Epidemiology Network (HyperGEN) study. Metabolic syndrome was defined using the
      joint harmonized criteria, and DNA methylation was assessed using the Illumina
      HumanMethylation450K Bead Chip assay on DNA extracted from buffy coat. Linear
      mixed effects regression models were used to examine the association between CpG
      methylation at > 450,000 CpG sites and metabolic syndrome adjusted for study
      covariates. Replication using DNA from a separate sample of 69 African-Americans,
      as well as meta-analysis combining both cohorts, was conducted. Results: Two
      differentially methylated CpG sites in the IGF2BP1 gene on chromosome 17
      (cg06638433; p value = 3.10 * 10- 7) and the ABCG1 gene on chromosome 21
      (cg06500161; p value = 2.60 * 10- 8) were identified. Results for the ABCG1 gene
      remained statistically significant in the replication dataset and meta-analysis.
      Conclusion: Metabolic syndrome was consistently associated with increased
      methylation in the ABCG1 gene in the discovery and replication datasets, a gene
      that encodes a protein in the ATP-binding cassette transporter family and is
      involved in intra- and extra-cellular signaling and lipid transport.

PMID- 29643946
TI  - TiO2-Nanofillers Effects on Some Properties of Highly- Impact Resin Using
      Different Processing Techniques.
AB  - Background: The criteria of conventional curing of polymethyl methacrylate do not
      match the standard properties of the denture base materials. Objectives: This
      research was conducted to investigate the addition of TiO2 nano practical on
      impact strength, thermal conductivity and color stability of acrylic resin cured
      by microwave in comparison to the conventional cured of heat-polymerized acrylic
      resin. Materials and Methods: 120 specimens made of high impact acrylic resin
      were divided into two main groups according to the type of curing (water bath,
      microwave), then each group was subdivided into two groups according to the
      addition of 3% TiO2 nano-fillers and control group (without the addition of TiO2
      0%). Each group was subdivided according to the type of test into 3 groups with
      10 specimens for each group. Data were statistically analyzed using Student t
      test to detect the significant differences between tested and control groups at
      significance level (P<0.05). Results: According to curing type methods, the
      results showed that there was a significant decrease in impact strength of
      microwaved cured resin, but there was no significant difference in the thermal
      conductivity and color stability of resin. In addition, by using nanofiller,
      there was a significant increase in the impact strength and color stability with
      the addition of 3% TiO2 nanofillers, but no significant difference was found in
      the thermal conductivity of the acrylic resin. Conclusion: The microwave curing
      of acrylic resin had no change in the color stability and thermal conductivity in
      comparison to the water bath, but the impact strength was decreased. The addition
      of 3% TiO2 improved the impact and the color stability, but the thermal
      conductivity did not change.

PMID- 29643947
TI  - Comparison of Saliva Nitric Oxide between Chronic Kidney Disease Before and After
      Dialysis and with Control Group.
AB  - Introduction: Chronic Kidney Disease (CKD) is a chronic progressive disorder and
      a major cause of death and disability in all countries. In the kidneys, Nitric
      Oxide (NO) has involved in several important cellular processes including
      glomerular and modular hemodynamics set-out, tubular - glomerular feedback
      reaction, renin releasing and extracellular fluid volume but NO can act as an
      inflammatory mediator and oxidative stress factor in high levels. Aim: The aim of
      this study was to evaluate salivary levels of NO in patients with chronic kidney
      disease on dialysis compared to the healthy subjects and evaluate the effect of
      dialysis on the level of NO in saliva. Materials & Methods: In this case-control
      study, 30 hemodialysis patients and 30 healthy controls that were matched for age
      and sex were selected. Unstimulated saliva samples were collected from all
      subjects. In the patient's group, half an hour before starting dialysis first
      sampling and two hours after the completion of dialysis second sampling were
      collected. NO concentration in the samples was measured by using the Griess
      method. For data analysis, SPSS software version 16, Mann Whitney-U and Wilcoxon
      test were used. The level of significance was considered 0.05. Results: Mann
      Whitney U test showed that the average concentration of salivary NO in patients
      with CKD (pre-dialysis and after dialysis) was higher than in the control group.
      The average concentration of salivary NO in patients with CKD was reduced after
      hemodialysis. Conclusion: Hemodialysis reduces salivary NO levels in CKD
      patients. It seems that hemodialysis has a role in decreasing the concentration
      of this inflammatory mediator and oxidative stress.

PMID- 29643948
TI  - Central Venous Oxygen Saturation as a Predictor of a Successful Spontaneous
      Breathing Trial from Mechanical Ventilation: A Prospective, Nested Case-Control
      Study.
AB  - Background: Weaning from mechanical ventilation is a key element in the care of
      critically ill patients, and Spontaneous Breathing Trial (SBT) is a crucial step
      in this procedure. This nested case-control study aimed to evaluate whether
      central oxygen saturation (ScvO2) values and their changes could independently
      predict the SBT outcome among mechanically ventilated patients. Methods: A
      prospective cohort of patients who were mechanically ventilated for at least
      48hours and fulfilled the criteria of readiness to wean constituted the study
      population. All patients attempted a SBT and were then categorized in SBT success
      group and SBT failure group, based on a combination of criteria which indicated
      whether SBT was successful or not. Multivariate binary logistic regression
      analysis was utilized to indicate the independent predictors of SBT success,
      while the Receiver Operating Characteristic (ROC) curves were used to demonstrate
      the diagnostic accuracy of these independent predictors. Results: Seventy-seven
      patients 69(18-86) years old; 62.3% male) constituted the study population. SBT
      was successful among 63.6% of them. A decrease in ScvO2 values (DeltaScvO2) < 4%
      between the beginning and the end of the trial independently predicted the
      successful outcome (OR=18.278; 95% CI=4.017-83.163), along with age, Hemoglobin
      concentration (Hb) and arterial oxygen saturation (SaO2). Diagnostic accuracy for
      DeltaScvO2 alone (ROC area=0.715) was slightly superior to that of either SaO2
      (0.625) or Hb (0.685) to predict SBT success. Conclusion: ScvO2 is an independent
      predictor of the weaning outcome and its evaluation may further facilitate the
      accurate categorization among those patients who pass or fail the SBT.

PMID- 29643949
TI  - High Secretion of Interleukin-6 and Increased MINCLE Receptor Expression Upon
      Exposure to Mycobacterial Cord Factor Analog Trehalose-6, 6-Dibehenate (TDB) in
      Patients with Takayasu Arteritis.
AB  - Introduction: Suspicion on the association between Takayasu Arteritis (TA) and
      Tubcerculosis (TB) has been in vogue for years. Prevalence of TB in TA is
      reported to be higher. We aimed to study innate immune responses in patients with
      TA on exposure to Trehalose-6,6-dibehenate (TDB), a synthetic analogue of
      Trehalose-6,6-Dimycolate (TDM, also known as mycobacterial cord factor) in
      comparison with healthy controls. Materials and Methods: Patients with type V TA,
      satisfying 1990 ACR criteria, and age and sex matched healthy controls were
      recruited. PBMCs were cultured with 5ug/ml, 50ug/ml or without any TDB for 48
      hours in RPMI medium inside a 5% Co2 incubator. IL-6, TNF-alpha and IL-17 were
      measured in cell culture supernatant, which was separated from the cells at the
      end of the incubation period. Gene expressions of IL-6, IL-8, TNFalpha, IFN
      gamma, MINCLE and BCL-10 were quantified in real time PCR using specific primers
      and SYBR green chemistry. Results: Twenty two TA patients and 21 healthy controls
      were recruited. Both patients and controls showed response by secreting IL-6 and
      TNF-alpha upon stimulation by TDB. Relative induction (TDB stimulated TA sample /
      unstimulated control) of IL-6 was significantly higher in TA [31.88(0.74-168)]
      patients as compared to healthy controls [1.931(0.644-8.21); p<0.002], when co
      cultured with 50ug/ml TDB. The expression of MINCLE, the TDB receptor was higher
      in TA samples than healthy controls upon TDB stimulation. Conclusion: Stimulation
      with mycobacterial synthetic analogue led to higher secretion of IL-6 and higher
      expression of MINCLE in PBMCs of patients with TA as compared to healthy
      controls.

PMID- 29643950
TI  - Higher Intraocular Pressure Levels Associated With Lower Hysteresis In Type 2
      Diabetes.
AB  - Aim: To investigate the differences of corneal biomechanic characteristics using
      Ocular Response Analyzer (ORA, Reichert; USA) on type 2 diabetics and healthy
      subjects. Methods: One hundred eyes of 100 subjects (between the ages of 17-91)
      who applied to Adnan Menderes University's Ophthalmology Clinic between January
      March 2015 were included in this study, 50 diabetics (Group 1) and 50 healthy
      controls (Group 2). The eyes included in the study were randomly chosen. Corneal
      Hysteresis (CH), Corneal Resistance Factor (CRF), Goldmann correlated Intraocular
      Pressure (IOPg) and corneal compensated Intraocular Pressure (IOPcc) of patients
      were measured by ORA. Detailed ophthalmological examinations were done for every
      subject. Kolmogorov-Smirnov test was used to analyze the distribution of
      quantitative variables and t test was used for the data that were normally
      distributed. Any p value <0.05 was considered as statistically significant.
      Results: The mean ages were 63.3+/-9.0 and 61.7+/-11.6 in Group 1 and 2,
      respectively (p=0.459). 25 (50.0%) were female, 25 (50.0%) were male in Group 1
      and 26 (52.0%) were female, 24 (48.0%) were male in Group 2 (p=1.000). Mean IOPcc
      values were 17.8+/-3.6 (12.1-29.0) and 16.0+/-3.1 (10.9-23.8) mmHg (p=0.006);
      mean IOPg values were 16.9+/-3.5 (10.9-25.9) and 15.4+/-2.9 (9.0-24.7) mmHg
      (p=0.032); mean CH values were 9.9+/-1.5 (6.1-13.3) and 10.5+/-1.7 (6.5-15.7)
      (p=0.080) and mean CRF values were 10.4+/-1.6 (7.5-14.0) and 10.5+/-1.7 (6.6
      15.4) (p=0.730) in Groups 1 and 2, respectively. Conclusions: There was no any
      statistical difference between the groups in terms of CH and CRF. However, mean
      CH and CRF values were found less in diabetic group. Corneal biomechanical
      differences seen in diabetic patients may be associated with a statistically
      significantly higher IOP measurements.

PMID- 29643951
TI  - Effectiveness of Surface Cleaning and Disinfection in a Brazilian Healthcare
      Facility.
AB  - Background: Failures in the processes of cleaning and disinfecting health service
      surfaces may result in the spread and transfer of pathogens that are often
      associated with healthcare-related infections and outbreaks. Aims: To assess the
      effectiveness of environmental surface cleaning and disinfection in a hospital
      clinic. Method: The study was conducted in a nursing ward with 45 beds. A total
      of 80 samples from five high-touch surfaces were evaluated before and after
      cleaning and disinfection, using the following methods: visual inspection,
      adenosine triphosphate bioluminescence assay, aerobic colony count,
      Staphylococcus aureus colony count, and evaluation of resistance to methicillin.
      The data analysis used nonparametric comparative and correlative tests to observe
      any differences in the pre- and post- cleaning and disinfection results for the
      surfaces assessed. Results: Effective cleaning and disinfection had a significant
      effect on only two surfaces when measured for the presence of adenosine
      triphosphate, the inner bathroom door handle (p=0.007) and the toilet bowl
      (p=0.01). When evaluated for Staphylococcus aureus colony count, the toilet flush
      handle also demonstrated a significant effect (p=0.04). Conclusion: The
      effectiveness of cleaning and disinfection of the surfaces tested was not
      satisfactory. An educational intervention is recommended for the cleaning and
      disinfection staff and the nursing team at the healthcare facility. Relevance to
      Clinical Practice: The data in the study revealed that daily hospital cleaning
      and disinfection in the sampled sites are not sufficient in medical and surgical
      wards. Hospital cleanliness must be reevaluated from the point of view of
      materials, such as an adequate supply of clean cloths, in addition to
      establishing more precise cleanliness protocols and accurate monitoring systems.

PMID- 29643952
TI  - Parastomal hernia - current knowledge and treatment.
AB  - Intestinal stoma creation is one of the most common surgical procedures. The most
      common long-term complication following stoma creation is parastomal hernia,
      which according to some authors is practically unavoidable. Statistical
      differences of its occurrence are mainly due to patient observation time and
      evaluation criteria. Consequently, primary prevention methods such as placement
      of prosthetic mesh and newly developed minimally invasive methods of stoma
      creation are used. It seems that in the light of evidence-based medicine, the
      best way to treat parastomal hernia is the one that the surgeon undertaking
      therapy is the most experienced in and is suited to the individuality of each
      patient, his condition and comorbidities. As a general rule, reinforcing the
      abdominal wall with a prosthetic mesh is the treatment of choice, with a low rate
      of complications and relapses over a long period of time. The current trend is to
      use lightweight, large pore meshes.

PMID- 29643953
TI  - Individualized laparoscopic B-ultrasound-guided microwave ablation for multifocal
      primary liver cancer.
AB  - Introduction: Liver cancer is one of the most common malignancies of the
      digestive system. Minimally invasive ablation procedures have become one of the
      major means for treating unresectable multifocal liver cancer and have been
      extensively applied in primary and metastatic liver cancer treatment.
      Laparoscopic B-ultrasound-guided microwave ablation is an example of the progress
      made in this field. Aim: To analyze and summarize the results of and experience
      with laparoscopic B-ultrasound-guided microwave ablation for multifocal primary
      liver cancer; moreover, the ablation effects were compared between tumors of
      different sizes. Material and methods: Laparoscope-guided needle ablation was
      conducted on 84 lesions from 32 patients with primary liver cancer based on tumor
      size, quantity, and location. Moreover, the perioperative data, ablation effects
      according to tumor size, and long-term follow-up results were analyzed. Results:
      Among the 84 nodules treated via microwave ablation, tumors measuring <= 3 cm
      demonstrated complete ablation upon imaging analysis conducted 1 month after
      surgery. Moreover, 5 of the tumors measuring > 3 cm demonstrated incomplete
      ablation. In these cases, a second procedure was performed, until imaging studies
      confirmed that complete ablation was achieved. Conclusions: Laparoscopic
      microwave ablation allows for precise puncture positioning, an effective ablation
      range, and safe and feasible surgery, which is especially suitable for liver
      tumors located in sites difficult to access.

PMID- 29643954
TI  - Cost-effectiveness of benign Wirsung duct strictures treatment in chronic
      pancreatitis.
AB  - Introduction: Chronic pancreatitis (CP) is an important problem for modern
      medicine, the healthcare system (Poland - NFZ) and the national insurance system
      (Poland - ZUS). The chronic nature of the disease, the lack of targeted treatment
      and the low mortality rate lead to an accumulation of patients who demand
      expensive treatment, both conservative and invasive. Rising costs in health care
      are forcing the need for a more cost-effective method of treatment. Aim: The
      primary aim of this study was to perform a retrospective calculation of costs in
      both surgical and endoscopic treatment, hospital stay, healthcare, and public
      insurance of patients suffering from chronic pancreatitis. Parallel quality of
      life analysis was performed. It was possible to develop a cost-effective
      therapeutic algorithm for patients with an uncomplicated stricture of Wirsung's
      duct within the Polish health care system. Results: In Poland, the hospital costs
      of endoscopic treatment of patients with chronic pancreatitis were higher than
      those of the surgical treatment group despite both resulting in a similar life
      quality. Conclusions: From a cost-effectiveness perspective, it was shown that
      surgical intervention is a more cost-effective therapy than endotherapy.
      Furthermore, patients with benign stricture of the main pancreatic duct in
      chronic pancreatitis should not be treated with endotherapy for longer than 12
      months.

PMID- 29643955
TI  - Implementation of laparoscopic approach in colorectal surgery - a single center's
      experience.
AB  - Introduction: Implementation of the laparoscopic approach in colorectal surgery
      has not happened as rapidly as in cholecystectomy, because of concerns about
      oncological safety. The results of controlled trials in multiple centers showed
      the method to be safe. Consequently, surgeons decided to try the approach with
      colorectal surgery. This process, in our clinic, began in earnest about four
      years ago. Aim: To analyze and present the clinical outcomes of applying the
      laparoscopic approach to colorectal surgery in a single center. Material and
      methods: We retrospectively identified patients from a hospital database who
      underwent colorectal surgery - laparoscopic and open - between 2013 and 2016. Our
      focus was on laparoscopic cases. Study points included operative time, duration
      of the hospital stay, postoperative mortality and rates of complications,
      conversion, reoperation and readmission. Results: Of 534 cases considered, the
      results showed that the relation between open and laparoscopic procedures had
      reversed, in favor of the latter method (2013: open: 82% vs. laparoscopic: 18%;
      2016: open: 22.4% vs. laparoscopic: 77.6%). The most commonly performed procedure
      was right hemicolectomy. The total complication rate was 22%. The total rate of
      conversion to open surgery was 9.3%. The postoperative mortality rate was 3%.
      Conclusions: Use of the laparoscopic approach in colorectal surgery has increased
      in recent years world-wide - including in Poland - but the technique is still
      underused. Rapid implementation of the miniinvasive method in colorectal surgery,
      in centers with previous laparoscopic experience, is not only safe and feasible,
      but also highly recommended.

PMID- 29643956
TI  - Serum cytokines in early prediction of anastomotic leakage following low anterior
      resection.
AB  - Introduction: Anastomotic leakage continues to be one of the most serious
      complications following low anterior resections. Early diagnosis of a leak is
      difficult but critical to minimize morbidity and mortality. Aim: To evaluate
      changes in serum concentrations of 27 different cytokines following low anterior
      resection, with the goal of finding new, early biomarkers of anastomotic leak.
      Material and methods: This is a prospective observational study that includes 32
      patients undergoing elective low anterior resection for rectal cancer. Blood
      samples were collected preoperatively and on postoperative day 3. Results: Five
      patients developed anastomotic leak (15%). On postoperative day 3, high
      sensitivity C-reactive protein (hs-CRP), interleukin (IL)-6, and regulated on
      activation, normal T cell expressed and secreted (RANTES) were significantly
      higher in patients with anastomotic leak, while IL-9 and fibroblast growth factor
      (FGF) 2 were significantly lower. Analysis of relative changes in the
      concentration of cytokines from preoperative to postoperative day 3 revealed a
      significant increase of IL-6 and granulocyte-colony stimulating factor (G-CSF) in
      patients with an anastomotic leak. Upon receiver operating curve (ROC) analysis,
      the performance of hs-CRP was found to be excellent (AUC = 0.99), and performance
      of DeltaIL-6, IL-6, RANTES, and FGF2 was good (AUC: 0.81-0.87). Patients who
      developed an anastomotic leak preoperatively had significantly lower levels of
      macrophage inflammatory protein-1 alpha (MIP-1alpha), monocyte chemotactic
      protein-1 (MCP-1), IL-8, FGF2, and G-CSF. Conclusions: The single most accurate
      serum biomarker of anastomotic leakage continues to be hs-CRP. However, when
      analyzing relative changes of cytokine levels, DeltaIL-6 appears to be a better
      leak predictor than CRP.

PMID- 29643957
TI  - Neopterin, kynurenine and tryptophan as new biomarkers for early detection of
      rectal anastomotic leakage.
AB  - Introduction: At present, there are no strong predictors, nor a useful scoring
      system, that clearly identifies patients at risk for anastomotic leakage. Aim:
      This study aimed to investigate a new method that assesses this risk by
      monitoring levels of neopterin, tryptophan, and kynurenine, in bodily fluids.
      Material and methods: This prospective study included patients who underwent
      elective rectal resection for carcinoma. The basic condition for inclusion was
      rectal anastomosis using the double-stapling technique. Preoperative levels of
      neopterin, tryptophan, kynurenine, and their ratios, were assessed with blood and
      urine samples. These levels were then monitored for 6 postoperative days in
      venous blood, urine, and abdominal drainage fluid. Results: A total of 42
      patients were enrolled in the study. Thirty-six patients underwent a laparoscopic
      resection and 6 patients had an open procedure. No differences were found among
      neopterin, tryptophan, and kynurenine serum levels. However, the groups were
      observed to have significant differences in the urinary neopterin/creatinine
      ratio: the preoperative neopterin/creatinine ratio was 139.5 MUmol/mol in the
      group with leakage, vs 114.8 MUmol/mol in the group without complications, p =
      0.037. The same results were observed during the postoperative period, p = 0.012.
      Additionally, the group with complications had a higher mean value of neopterin
      in drainage fluid, p = 0.048. Conclusions: Our study demonstrated that high
      preoperative levels of urinary neopterin could be interpreted as a risk for
      anastomotic leakage. Moreover, pathological levels of neopterin in urine and
      abdominal drainage fluid could be useful for early identification of anastomotic
      leakage during the postoperative period prior to its clinical development.

PMID- 29643958
TI  - Outcomes and complications of self-expanding metal stent placement for malignant
      colonic obstruction in a single-center study.
AB  - Introduction: Approximately 20% of cases of colorectal cancer are accompanied by
      acute colonic obstruction. While emergency colonic surgery is associated with
      high mortality and morbidity rates, placement of a self-expanding metal stent
      (SEMS) has been suggested as an alternative method. The SEMS placement can serve
      as either a definitive treatment in palliative cases or a bridge to surgery. Aim:
      To summarize the experience of our center in the treatment of malignant colonic
      obstruction using SEMS placement. Material and methods: A retrospective review
      was conducted of all patients who underwent a SEMS placement for colorectal
      stricture in the study period. The procedures were performed under fluoroscopic
      guidance with colonoscopic assistance, and uncovered stents were used in all
      patients. Results: The study population consisted of 28 patients treated with
      SEMS placement due to malignant colonic obstruction. The majority of procedures
      were performed with palliative intent. The overall technical success rate was
      96.5%, and clinical success was achieved in all of the successfully placed SEMSs.
      One fatal complication due to colonic perforation occurred. In the bridge-to
      surgery group, all patients experienced tumor resection with no stoma creation.
      Conclusions: The SEMS placement is an optimal treatment in the vast majority of
      acute colonic obstruction cases. Due to the possibility of potentially fatal
      complications, SEMS procedures should be performed by proficient endoscopists.

PMID- 29643959
TI  - Hybrid appendectomy with classic trocar on McBurney's point.
AB  - Introduction: Appendectomy is still the most commonly performed intra-abdominal
      operation worldwide. Interestingly, it has not reached the same popularity as
      other laparoscopic surgical procedures. Although multiple techniques have been
      described, a standard approach has not been described for the laparoscopic
      technique yet. Aim: To perform hybrid appendectomy for acute appendicitis on
      McBurney's point, aiming to perform an easier and quicker procedure while
      limiting the trauma to the abdominal wall by obtaining the advantages of both
      laparoscopic and open techniques. Material and methods: We retrospectively
      evaluated the results of 24 patients on whom we had performed hybrid appendectomy
      with an optical trocar on McBurney's point for acute appendicitis in 1 year in
      terms of demographics, operative time, complications, hospital stay and cosmetic
      results. Results: Twenty-one of the patients underwent hybrid appendectomy with a
      one-optic trocar on McBurney's point. The mean operative time was 21.4 +/-6.2
      min. We did not encounter any postoperative complications in any of the patients.
      The median hospital stay was 1.2 +/-1.0 days. The postoperative scar was minimal.
      Conclusions: This technique is defined in the literature for the first time, and
      it is easy and feasible for the surgeons. It may reduce the operative time and
      costs when compared to the conventional laparoscopic technique, but prospective
      studies with more patients are needed for more certain results.

PMID- 29643960
TI  - Unexpected pathological findings after laparoscopic cholecystectomy - analysis of
      1131 cases.
AB  - Introduction: Gallbladder specimens are routinely sent for histopathological
      examination after cholecystectomy in order to rule out the presence of unexpected
      pathological findings. Aim: To establish the overall incidence of unexpected
      pathological findings in patients who underwent laparoscopic cholecystectomy for
      symptomatic gallbladder disease and determine whether the macroscopic appearance
      of the gallbladder in ultrasound examination could be a valid method for
      identifying patients with gallbladder malignancy. Material and methods: A
      retrospective study was conducted between 2013 and 2015. All histological reports
      (n = 1131) after cholecystectomy were searched for unexpected pathological
      findings. In cases where unexpected pathological findings were identified the
      additional analysis of preoperative abdominal ultrasound examination (USG) was
      done to determine the usefulness of USG in diagnosis of gallbladder malignancy.
      Results: Of the 1131 patients included in the study, 356 (31.47%) were male and
      774 (68.43%) were female. Unexpected pathological findings were present in 21
      cases. The overall incidence of unexpected pathological findings was 1.86%. Only
      in 5 patients were suspicious appearances of gallbladder observed in preoperative
      ultrasound examination. In 16 patients there was no suspicion of malignancy. The
      positive predictive value of USG was 0.238. Conclusions: The incidence of
      unexpected pathological findings after laparoscopic cholecystectomy was 1.86%.
      Ultrasonography has low positive predictive value for identifying patients with
      malignant findings in a gallbladder specimen.

PMID- 29643961
TI  - Cecal intubation rates in different eras of endoscopic technological development.
AB  - Introduction: Colonoscopy plays a critical role in colorectal cancer (CRC)
      screening and has been widely regarded as the gold standard. Cecal intubation
      rate (CIR) is one of the well-defined quality indicators used to assess
      colonoscopy. Aim: To assess the impact of new technologies on the quality of
      colonoscopy by assessing completion rates. Material and methods: This was a dual
      center study at the 2nd Department of Surgery at Jagiellonian University Medical
      College and at the Specialist Center "Medicina" in Krakow, Poland. The CIR and
      cecal intubation time (CIT) in three different eras of technological advancement
      were determined. The study enrolled 27 463 patients who underwent colonoscopy as
      part of a national CRC screening program. The patients were divided into three
      groups: group I - 3408 patients examined between 2000 and 2003 (optical
      endoscopes); group II - 10 405 patients examined between 2004 and 2008 (standard
      electronic endoscopes); and group III - 13 650 patients examined between 2009 and
      2014 (modern endoscopes). Results: There were statistically significant
      differences in the CIR between successive eras. The CIR in group I (2000-2003)
      was 69.75%, in group II (2004-2008) was 92.32%, and in group III (2009-2014) was
      95.17%. The mean CIT was significantly reduced in group III. Conclusions: Our
      study shows that the technological innovation of novel endoscopy devices has a
      great influence on the effectiveness of the CRC screening program. The new era of
      endoscopic technological development has the potential to reduce examination
      related patient discomfort, obviate the need for sedation and increase diagnostic
      yields.

PMID- 29643962
TI  - Ethnicity-related differences in inguinal canal dimensions between African and
      Caucasian populations and their potential impact on the mesh size for open and
      laparoscopic groin hernia repair in low-resource countries in Africa.
AB  - Introduction: Access to surgery in Africa is significantly limited. Treatment
      outcomes in Africa differ significantly compared to those achieved in Europe or
      the US. Therefore, to popularise tension-free repair, it is essential to
      determine the economically justified mesh size for the African population. Aim:
      To conduct anthropometric evaluation of the inguinal canal in African and
      European patients to determine its potential consequences for the mesh size for
      open and laparoscopic hernia repair. Material and methods: The measurements were
      made in 44 adult males in Africa (group I) and were compared to measurements in
      45 consecutive Caucasian males (group II). The mean age of patients was
      respectively 48.3 and 51.2 years. Results: There was no statistically significant
      difference in the internal ring diameter between groups (2.2 vs. 2.1 cm; p =
      0.58). The distance between the pubic tubercle and the inferomedial border of the
      internal inguinal ring was significantly shorter in group I (3.8 vs. 5.1 cm; p <
      0.001). A similar difference was found in the length of transverse arch
      aponeurosis (2.9 vs. 4.0 cm; p < 0.001). The distance between the pubic tubercle
      and anterior superior iliac spine in group I was approximately 2 cm shorter on
      each side (10.0 vs. 11.8 cm; p < 0.001). Conclusions: The anatomical differences
      in inguinal dimensions between Central African and European populations support
      the potential need to adjust the standard size of synthetic mesh used for hernia
      repair to the needs of local populations. The significantly smaller dimensions of
      the inguinal canal in African males may allow the use of smaller meshes.

PMID- 29643963
TI  - Age is not associated with increased surgical complications in patients after
      laparoscopic sleeve gastrectomy.
AB  - Introduction: Age is considered as a risk factor in bariatric surgery. The
      observation was made on the basis of results from studies where patients
      underwent different type of surgery, but laparoscopic sleeve gastrectomy (LSG)
      was not among them. It is necessary to reevaluate the association of age with
      adverse events in the group of patients after LSG. Aim: To investigate the
      association of age with surgery-related adverse events in patients after LSG.
      Material and methods: Retrospective analysis of medical data was performed. The
      study involved 345 patients who underwent LSG in our institution between January
      2013 and December 2014. The patients were subdivided by age into four groups
      according to quartiles. In 30-day follow-up adverse events were evaluated. We
      considered the presence of the following events as the endpoint of our study:
      death, medical events and surgical events. Results: In general, we observed
      adverse events in 36 (10.4%) patients. The mortality rate in our study was 0.59%.
      Nineteen events were surgical and 18 medical. In 1 patient a surgical event was
      associated with a medical event. Bleeding was the most common surgical event and
      was observed in 17 (4.9%) cases. Age was not associated with surgical events (OR
      = 1.032, 95% CI: 0.991-1.075, p = 0.33) or medical events (OR = 0.997, 95% CI:
      0.956-1.039, p = 0.89). Conclusions: The LSG is a safe bariatric procedure with
      low mortality. Bleeding is the most frequent surgical complication. Our findings
      suggest that age is not associated with increased risk of surgical or medical
      adverse events after LSG.

PMID- 29643964
TI  - More stapler firings increase the risk of perioperative morbidity after
      laparoscopic sleeve gastrectomy.
AB  - Introduction: Staple-line bleeding and leakage are the most common serious
      complications of laparoscopic sleeve gastrectomy. The relationship between
      multiple stapler firings and higher risk of postoperative complications is well
      defined in colorectal surgery but has not been addressed in bariatric procedures
      so far. Identification of new factors such as "the numbers of stapler firings
      used during laparoscopic sleeve gastrectomy (LSG)" as a predictor for
      complications can lead to optimization of the patient care at bariatric centers.
      Aim: To determine the association between perioperative morbidity and the number
      of stapler firings during laparoscopic sleeve gastrectomy. Material and methods:
      This observational study was based on retrospective analysis of prospectively
      collected data in patients operated on for morbid obesity in a teaching
      hospital/tertiary referral center for general surgery. The patients who underwent
      LSG were analyzed in terms of the number of stapler firings used as a new
      potential risk predictor for postoperative complications after surgery, adjusting
      for other patient- and treatment-related factors. The study included 333 patients
      (209 women, 124 men, mean age: 40 +/-11). Results: During the first 30 days after
      surgery, complications were observed in 18 (5.41%) patients. Multivariate
      analysis showed that prolonging operative time increased morbidity (every minute,
      OR = 1.01; 95% CI: 1.00-1.02) and the complication rate increased with the number
      of stapler firings (every firing, OR = 1.91; 95% CI: 1.09-3.33; p = 0.023).
      Conclusions: Additional stapler firings above the usual number and a prolonged
      operation should alert a surgeon and the whole team about increased risk of
      postoperative complications.

PMID- 29643965
TI  - Video-assisted-thoracoscopic surgery in left-to-right Nuss procedure for pectus
      excavatum for prevention of serious complications - technical aspects based on
      1006 patients.
AB  - Introduction: Additional use of the video-assisted thoracoscopic surgery (VATS)
      technique in the Nuss procedure has been globally accepted for the improvement of
      safety of surgical treatment as well as for decreased frequency of serious
      intraoperative and postoperative complications. Aim: To evaluate VATS in surgical
      treatment of patients with pectus excavatum by the left-to-right Nuss procedure
      for prevention of serious intra- and postoperative complications. Material and
      methods: From 2002 to 2016, 1006 patients with pectus excavatum aged 7 to 62
      years (mean: 18.6) underwent the Nuss procedure. There were 796 males and 210
      females. The clinical records of all patients were analyzed retrospectively. The
      follow-up varied from 1 to 172 months (mean: 80.7 +/-43). Results: The early 30
      day postoperative mortality was zero. Early thoracoscopy-dependent postoperative
      complications, the majority transient and non-life-threatening, occurred in 35.6%
      of patients. The most frequent complication was pneumothorax, diagnosed in 24.5%
      of patients. Two patients required repeat surgery. One patient required VATS
      pleurectomy due to persistent postoperative air leakage. In another patient left
      thoracotomy following bleeding from the pleural cavity was performed.
      Conclusions: The use of VATS in the left-to-right Nuss procedure for pectus
      excavatum ensures the safety of surgical treatment and minimizes the occurrence
      of serious intra- and postoperative complications concerning injury of the
      mediastinum, lung, diaphragm or abdominal cavity.

PMID- 29643966
TI  - Cosmetic effects of skin-crease camouflage incision versus longitudinal incision
      following carotid endarterectomy.
AB  - Introduction: Despite the increasing use of carotid angioplasty and stenting
      (CAS), carotid endarterectomy (CEA) nonetheless remains a more medically
      beneficial method of treatment for carotid artery stenosis. Therefore, one
      possibility for progress within this procedure may be to use minimally invasive
      carotid surgery, especially when the scar is in plain sight: the use of the
      natural wrinkles (skin crease) as a camouflage of the skin incision provides
      significant cosmetic improvements. Aim: To compare the cosmetic effects of
      classic and trans-wrinkle CEA. To assess the distance between the carotid artery
      bifurcation (CAB) and the skin-crease incision whilst attempting CEA. Material
      and methods: It was a randomized prospective study with two groups: patients
      undergoing classic surgery (control group; n = 100) and skin-crease trans-wrinkle
      camouflaged CEA (study group; n = 100). Follow-up was at 2 months and 1 year.
      Results: The medical results of the treatment were similar in both groups. The
      cumulative count of strokes and myocardial infarctions was 0.5% within 30 days,
      and after one year 3.5% (and 5.5% including cases of death). The superiority of
      the transverse crease being hidden compared to the conventional longitudinal
      technique was proven in the Patient and Observer Scar Assessment Scale (POSAS)
      score, respectively 11.4 +/-1.0 vs. 14.1 +/-3.4 (p = 0.0001) after 2 months and
      13.5 +/-2.8 vs. 14.1 +/-3.4 (p = 0.039) after a year. Conclusions: Trans-wrinkle
      incision gives better cosmetic results, can be safely performed in most cases,
      and offers a comfortable approach during CEA.

PMID- 29643967
TI  - Minimally invasive treatment of intrahepatic cholangiolithiasis after stricture
      of hepaticojejunal anastomosis.
AB  - The aim of the study was to improve the results of treatment of patients with
      intrahepatic cholangiolithiasis for hepaticojejunostomy stricture with use of
      miniinvasive methods. In our centre during the period from 2002 till 2016 were
      treated in 58 patients with hepaticojejunostomy strictures. Thirteen patients
      from their was coexistant intrahepatic cholangiolithiasis. Forty-six (79.3%)
      patients was performed rehepaticojejunostomy. Twelve patients was performed a
      minimally invasive intervention such as laser recanalisation using double balloon
      enteroscopy (7 patients) and lithoextraction with double balloon enteroscopy (1),
      transhepatic cholangioscopy (2 patients) with laser lithotripsy (1), balloon
      dilatation of the stricture rehepaticojejunostomosis (4), lithoextraction (4),
      including with double balloon enteroscopy ("randevoux" procedure) (1), stenting
      (2). We observed several complication such as cholangitis (5); recurrent
      cholangiolithiasis (1); restricture of rehepaticojejunostomosis (2). Miniinvasive
      endoscopic techniques treatment and endobiliary correction of
      rehepaticojejunostomosis strictures and cholangiolithiasis have shown good
      results.

PMID- 29643968
TI  - Gastric wall thickness and stapling in laparoscopic sleeve gastrectomy - a
      literature review.
AB  - Despite the growing experience of bariatric surgeons in performing laparoscopic
      sleeve gastrectomy, the number of complications involving staple line leaks
      remains constant. Hence a solution to avoid such complications is still sought. A
      defect of the staple line may be the consequence of an inappropriate choice of
      staple size in relation to gastric wall thickness. Due to the variable nature of
      gastric wall thickness, the choice of proper staple height is not obvious. In the
      few studies in which gastric wall thickness was measured, it was observed to
      decrease gradually from the antrum to the fundus. However, the authors are
      divided on the issue of whether gender and body mass index influence gastric wall
      thickness. The question whether there are other perioperative factors that would
      allow gastric wall thickness to be predicted remains unanswered.

PMID- 29643969
TI  - Electromagnetic Tracker for Active Handheld Robotic Systems.
AB  - We describe the development of the In-Loop Electromagnetic Tracker (ILEMT),
      designed to meet the demanding latency and resolution requirements for active
      stabilization of hand motion during precision manipulations such as microsurgery.
      The prototype surpasses the fastest commercial EM trackers by > 4* in root
      bandwidth/resolution and 2* in latency. The use of two widely spaced carrier
      frequencies (e.g., 300 Hz and 10 kHz) enables a particularly simple way of
      reducing the eddy-current interference caused by nonferrous metals present in the
      workspace. Previously, metal compatibility has only been achieved at a large cost
      to measurement speed.

PMID- 29643970
TI  - In Vitro Degradation Behaviors of Manganese-Calcium Phosphate Coatings on an Mg
      Ca-Zn Alloy.
AB  - In order to decrease the degradation rate of magnesium (Mg) alloys for the
      potential orthopedic applications, manganese-calcium phosphate coatings were
      prepared on an Mg-Ca-Zn alloy in calcium phosphating solutions with different
      addition of Mn2+. Influence of Mn content on degradation behaviors of phosphate
      coatings in the simulated body fluid was investigated to obtain the optimum
      coating. With the increasing Mn addition, the corrosion resistance of the
      manganese-calcium phosphate coatings was gradually improved. The optimum coating
      prepared in solution containing 0.05 mol/L Mn2+ had a uniform and compact
      microstructure and was composed of MnHPO4.3H2O, CaHPO4.2H2O, and Ca3(PO4)2. The
      electrochemical corrosion test in simulated body fluid revealed that polarization
      resistance of the optimum coating is 36273 Omegacm2, which is about 11 times
      higher than that of phosphate coating without Mn addition. The optimum coating
      also showed the most stable surface structure and lowest hydrogen release in the
      immersion test in simulated body fluid.

PMID- 29643971
TI  - Scanning Electron Microscopic Studies of Microwave Sintered Al-SiC Nanocomposites
      and Their Properties.
AB  - Al-metal matrix composites (AMMCs) reinforced with diverse volume fraction of SiC
      nanoparticles were synthesized using microwave sintering process. The effects of
      the reinforcing SiC particles on physical, microstructure, mechanical, and
      electrical properties were studied. The phase, microstructural, and surface
      analyses of the composites were systematically conducted using X-ray diffraction
      (XRD), scanning electron microscope (SEM), and surface profilometer techniques,
      respectively. The microstructural examination revealed the homogeneous
      distribution of SiC particles in the Al matrix. Microhardness and compressive
      strength of nanocomposites were found to be increasing with the increasing volume
      fraction of SiC particles. Electrical conductivity of the nanocomposites
      decreases with increasing the SiC content.

PMID- 29643972
TI  - [Translated Title: Participatory research to develop a school violence
      observation instrument].
AB  - School violence has been recognized worldwide as a public health problem that
      negatively impacts the educational process. However, in Puerto Rico official
      statistics and the media generally focus on isolated incidents of extreme
      violence in which weapons are used or property is destroyed. Little data is
      available about the most common forms of violence that often occur in schools on
      a daily basis. The Instrumento de Observacion de Violencia Escolar (INOVE),
      developed with the input of school communities participating in Project VIAS
      (Violence and Asthma Health Disparity Network) of Universidad del Este (UNE), was
      used in this study to gather information about the characteristics of violence in
      two Puerto Rican schools. Among the study findings we highlight gender
      differences in observed violence and aggressive games and interactions between
      students. The data collected have served as a basis for decision-making regarding
      violence prevention in participating schools and have implications for the
      development of prevention strategies and programs.

PMID- 29643973
TI  - Epigenetic versus Genetic Deregulation of the KEAP1/NRF2 Axis in Solid Tumors:
      Focus on Methylation and Noncoding RNAs.
AB  - Oxidative and electrophilic changes in cells are mainly coordinated by the
      KEAP1/NRF2 (Kelch-like erythroid-derived cap-n-collar homology- (ECH-) associated
      protein-1/nuclear factor (erythroid-derived 2)-like 2) axis. The physical
      interaction between these two proteins promotes the expression of several
      antioxidant defense genes in response to exogenous and endogenous insults. Recent
      studies demonstrated that KEAP1/NRF2 axis dysfunction is also strongly related to
      tumor progression and chemo- and radiotherapy resistance of cancer cells. In
      solid tumors, the KEAP1/NRF2 system is constitutively activated by the loss of
      KEAP1 or gain of NFE2L2 functions that leads to its nuclear accumulation and
      enhances the transcription of many cytoprotective genes. In addition to point
      mutations, epigenetic abnormalities, as aberrant promoter methylation, and
      microRNA (miRNA) and long noncoding RNA (lncRNA) deregulation were reported as
      emerging mechanisms of KEAP1/NRF2 axis modulation. This review will summarize the
      current knowledge about the epigenetic mechanisms that deregulate the KEAP1/NRF2
      cascade in solid tumors and their potential usefulness as prognostic and
      predictive molecular markers.

PMID- 29643974
TI  - SIRT3: A New Regulator of Cardiovascular Diseases.
AB  - Cardiovascular diseases (CVDs) are the leading causes of death worldwide, and
      defects in mitochondrial function contribute largely to the occurrence of CVDs.
      Recent studies suggest that sirtuin 3 (SIRT3), the mitochondrial NAD+-dependent
      deacetylase, may regulate mitochondrial function and biosynthetic pathways such
      as glucose and fatty acid metabolism and the tricarboxylic acid (TCA) cycle,
      oxidative stress, and apoptosis by reversible protein lysine deacetylation. SIRT3
      regulates glucose and lipid metabolism and maintains myocardial ATP levels, which
      protects the heart from metabolic disturbances. SIRT3 can also protect
      cardiomyocytes from oxidative stress-mediated cell damage and block the
      development of cardiac hypertrophy. Recent reports show that SIRT3 is involved in
      the protection of several heart diseases. This review discusses the progress in
      SIRT3-related research and the role of SIRT3 in the prevention and treatment of
      CVDs.

PMID- 29643975
TI  - Physiological Hypoxia Enhances Stemness Preservation, Proliferation, and
      Bidifferentiation of Induced Hepatic Stem Cells.
AB  - Induced hepatic stem cells (iHepSCs) have great potential as donors for liver
      cell therapy due to their self-renewal and bipotential differentiation
      properties. However, the efficiency of bidifferentiation and repopulation
      efficiency of iHepSCs is relatively low. Recent evidence shows that physiological
      hypoxia, a vital factor within stem cell "niche" microenvironment, plays key
      roles in regulating tissue stem cell biological behaviors including proliferation
      and differentiation. In this study, we found that physiological hypoxia (10% O2)
      enhanced the stemness properties and promoted the proliferation ability of
      iHepSCs by accelerating G1/S transition via p53-p21 signaling pathway. In
      addition, short-term hypoxia preconditioning improved the efficiency of hepatic
      differentiation of iHepSCs, and long-term hypoxia promoted cholangiocytic
      differentiation but inhibited hepatic differentiation of iHepSCs. These results
      demonstrated the potential effects of hypoxia on stemness preservation,
      proliferation, and bidifferentiation of iHepSCs and promising perspective to
      explore appropriate culture conditions for therapeutic stem cells.

PMID- 29643977
TI  - Role and Possible Mechanisms of Sirt1 in Depression.
AB  - Depression is a common, devastating illness. Due to complicated causes and
      limited treatments, depression is still a major problem that plagues the world.
      Silent information regulator 1 (Sirt1) is a deacetylase at the consumption of
      NAD+ and is involved in gene silencing, cell cycle, fat and glucose metabolism,
      cellular oxidative stress, and senescence. Sirt1 has now become a critical
      therapeutic target for a number of diseases. Recently, a genetic study has
      received considerable attention for depression and found that Sirt1 is a
      potential gene target. In this short review article, we attempt to present an up
      to-date knowledge of depression and Sirt1 of the sirtuin family, describe the
      different effects of Sirt1 on depression, and further discuss possible mechanisms
      of Sirt1 including glial activation, neurogenesis, circadian control, and
      potential signaling molecules. Thus, it will open a new avenue for clinical
      treatment of depression.

PMID- 29643976
TI  - Autophagy Modulation in Cancer: Current Knowledge on Action and Therapy.
AB  - In the last two decades, accumulating evidence pointed to the importance of
      autophagy in various human diseases. As an essential evolutionary catabolic
      process of cytoplasmatic component digestion, it is generally believed that
      modulating autophagic activity, through targeting specific regulatory actors in
      the core autophagy machinery, may impact disease processes. Both autophagy
      upregulation and downregulation have been found in cancers, suggesting its dual
      oncogenic and tumor suppressor properties during malignant transformation.
      Identification of the key autophagy targets is essential for the development of
      new therapeutic agents. Despite this great potential, no therapies are currently
      available that specifically focus on autophagy modulation. Although drugs like
      rapamycin, chloroquine, hydroxychloroquine, and others act as autophagy
      modulators, they were not originally developed for this purpose. Thus, autophagy
      may represent a new and promising pharmacologic target for future drug
      development and therapeutic applications in human diseases. Here, we summarize
      our current knowledge in regard to the interplay between autophagy and malignancy
      in the most significant tumor types: pancreatic, breast, hepatocellular,
      colorectal, and lung cancer, which have been studied in respect to autophagy
      manipulation as a promising therapeutic strategy. Finally, we present an overview
      of the most recent advances in therapeutic strategies involving autophagy
      modulators in cancer.

PMID- 29643978
TI  - The In Vitro Antioxidant Activity and Inhibition of Intracellular Reactive Oxygen
      Species of Sweet Potato Leaf Polyphenols.
AB  - The in vitro antioxidant activity and inhibition of intracellular reactive oxygen
      species (ROS) of the total and individual phenolic compounds from Yuzi No. 7
      sweet potato leaves were investigated in this study. Sweet potato leaf
      polyphenols possessed significantly higher antioxidant activity than ascorbic
      acid, tea polyphenols, and grape seed polyphenols. Among the individual phenolic
      compounds, caffeic acid showed the highest antioxidant activity, followed by
      monocaffeoylquinic acids and dicaffeoylquinic acids, while 3,4,5-tri-O
      caffeoylquinic acid showed the lowest value. Sweet potato leaf polyphenols could
      significantly decrease the level of intracellular ROS in a dose-dependent manner.
      The order of the inhibiting effect of individual phenolic compounds on the
      intracellular ROS level was not in accordance with that of antioxidant activity,
      suggesting that there was no direct relationship between antioxidant activity and
      intracellular ROS-inhibiting effect. Sweet potato leaves could be a good source
      of biologically active polyphenols with multiple applications in the development
      of foods, health products, pharmaceuticals, and cosmetics.

PMID- 29643979
TI  - Cardiac Autonomic Neuropathy as a Result of Mild Hypercaloric Challenge in
      Absence of Signs of Diabetes: Modulation by Antidiabetic Drugs.
AB  - Cardiac autonomic neuropathy (CAN) is an early cardiovascular complication of
      diabetes occurring before metabolic derangement is evident. The cause of CAN
      remains elusive and cannot be directly linked to hyperglycemia. Recent clinical
      data report cardioprotective effects of some antidiabetic drugs independent of
      their hypoglycemic action. Here, we used a rat model receiving limited daily
      increase in calories from fat (HC diet) to assess whether mild metabolic
      challenge led to CAN in absence of interfering effects of hyperglycemia, glucose
      intolerance, or obesity. Rats receiving HC diet for 12 weeks showed reduction in
      baroreceptor sensitivity and heart rate variability despite lack of change in
      baseline hemodynamic and cardiovascular structural parameters. Impairment of
      cardiac autonomic control was accompanied with perivascular adipose inflammation
      observed as an increased inflammatory cytokine expression, together with
      increased cardiac oxidative stress, and signaling derangement characteristic of
      diabetic cardiomyopathy. Two-week treatment with metformin or pioglitazone
      rectified the autonomic derangement and corrected the molecular changes.
      Switching rats to normal chow but not to isocaloric amounts of HC for two weeks
      reversed CAN. As such, we conclude that adipose inflammation due to increased fat
      intake might underlie development of CAN and, hence, the beneficial effects of
      metformin and pioglitazone.

PMID- 29643980
TI  - Perillaldehyde Inhibits AHR Signaling and Activates NRF2 Antioxidant Pathway in
      Human Keratinocytes.
AB  - The skin covers the outer surface of the body, so the epidermal keratinocytes
      within it are susceptible to reactive oxygen species (ROS) generated by
      environmental pollutants such as benzo(a)pyrene (BaP), a potent activator of aryl
      hydrocarbon receptor (AHR). Antioxidant activity is generally mediated by the
      nuclear factor-erythroid 2-related factor-2 (NRF2) and heme oxygenase-1 (HO1)
      axis in human keratinocytes. Perillaldehyde is the main component of Perilla
      frutescens, which is a medicinal antioxidant herb traditionally consumed in East
      Asia. However, the effect of perillaldehyde on the AHR/ROS and/or NRF2/HO1
      pathways remains unknown. In human keratinocytes, we found that perillaldehyde
      (1) inhibited BaP-induced AHR activation and ROS production, (2) inhibited
      BaP/AHR-mediated release of the CCL2 chemokine, and (3) activated the NRF2/HO1
      antioxidant pathway. Perillaldehyde is thus potentially useful for managing
      inflammatory skin diseases or disorders related to oxidative stress.

PMID- 29643981
TI  - Nephroprotective Effect of Sonchus oleraceus Extract against Kidney Injury
      Induced by Ischemia-Reperfusion in Wistar Rats.
AB  - Introduction: Kidney ischemia-reperfusion (I/R) injury is the main cause of
      delayed graft function in solid organ transplantation. Sonchus oleraceus is a
      plant with well-known antioxidant and anti-inflammatory activities; however, its
      effects on renal I/R are unknown. Objective: To evaluate whether S. oleraceus
      extract (S.O.e.) has nephroprotective activity in an I/R model in Wistar rats.
      Materials and Methods: Animal groups (n = 6): sham, I/R (45 min/15 h), S.O.e (300
      mg/kg p.o.), and S.O.e + I/R (300 mg/kg, p.o.; 45 min/15 h). Renal function,
      proinflammatory cytokines, alanine aminotransferase, markers of oxidative stress,
      and histology were evaluated. Results: None of the mediators evaluated differed
      significantly between the S.O.e and sham groups. Levels of blood urea nitrogen
      (BUN), creatinine, malondialdehyde (MDA), and proinflammatory cytokines were
      higher, and superoxide dismutase (SOD) was lower in the I/R group than in the
      sham group. Histology showed tubular epithelial necrosis in the medulla and
      cortex in the I/R group. In the S.O.e + I/R group, S.O.e pretreatment attenuated
      the I/R-induced increases in BUN, creatinine, MDA, and proinflammatory cytokines
      induced, SOD was maintained, and histology showed discontinuous necrosis in the
      medulla but no necrosis in the cortex. Conclusions: S.O.e was neither hepatotoxic
      nor nephrotoxic. S.O.e. pretreatment showed a nephroprotective effect against
      I/R.

PMID- 29643983
TI  - The Value of Remotely Sensed Information: The Case of GRACE-Enhanced Drought
      Severity Index.
AB  - A decision framework is developed for quantifying the economic value of
      information (VOI) from the Gravity Recovery and Climate Experiment (GRACE)
      satellite mission for drought monitoring, with a focus on the potential
      contributions of groundwater storage and soil moisture measurements from the
      GRACE Data Assimilation (GRACE-DA) System. The study consists of: (a) the
      development of a conceptual framework to evaluate the socioeconomic value of
      GRACE-DA as a contributing source of information to drought monitoring; (b)
      structured listening sessions to understand the needs of stakeholders who are
      affected by drought monitoring; (c) econometric analysis based on the conceptual
      framework that characterizes the contribution of GRACE-DA to the US Drought
      Monitor (USDM) in capturing the effects of drought on the agricultural sector;
      and (d) a demonstration of how the improved characterization of drought
      conditions may influence decisions made in a real-world drought disaster
      assistance program. Results show that GRACE-DA has the potential to lower the
      uncertainty associated with our understanding of drought, and that this improved
      understanding has the potential to change policy decisions that lead to tangible
      societal benefits.

PMID- 29643984
TI  - The glucocorticoid receptor in recipient cells keeps cytokine secretion in acute
      graft-versus-host disease at bay.
AB  - Graft-versus-host disease (GvHD) is a life-threatening complication of
      hematopoietic stem cell transplantation (HSCT), which is caused by allogeneic T
      cells recognizing molecules of the recipient as foreign. Endogenous
      glucocorticoids (GC) released from the adrenal gland are crucial in regulating
      such inflammatory diseases. Here we demonstrate that genetically engineered mice,
      that are largely unresponsive to GC, suffer from aggravated clinical symptoms and
      increased mortality after HSCT, effects that could be tempered by neutralization
      of IL-6. Interestingly, selective ablation of the GC receptor (GR) in recipient
      myeloid cells resulted in fulminant disease as well. While histopathological
      analysis of the jejunum failed to reveal any differences between sick mice of
      both genotypes, systemic IL-6 and TNFalpha secretion was strongly increased in
      transplanted mice lacking the GR in myeloid cells briefly before the majority of
      them succumbed to the disease. Collectively, our findings reveal an important
      role of the GR in recipient cells in limiting the cytokine storm caused by GvHD
      induction.

PMID- 29643985
TI  - Replication-incompetent gammaretroviral and lentiviral vector-based insertional
      mutagenesis screens identify prostate cancer progression genes.
AB  - Replication-incompetent gammaretroviral (gammaRV) and lentiviral (LV) vectors
      have both been used in insertional mutagenesis screens to identify cancer
      drivers. In this approach the vectors stably integrate in the host cell genome
      and induce cancers by dysregulating nearby genes. The cells that contain a
      retroviral vector provirus in or near a proto-oncogene or tumor suppressor are
      preferentially enriched in a tumor. gammaRV and LV vectors have different
      integration profiles and genotoxic potential, making them potentially
      complementary tools for insertional mutagenesis screens. We performed screens
      using both gammaRV and LV vectors to identify driver genes that mediate
      progression of androgen-independent prostate cancer (AIPC) using a xenotransplant
      mouse model. Vector transduced LNCaP cells were injected orthotopically into the
      prostate gland of immunodeficient mice. Mice that developed tumors were castrated
      to create an androgen-deficient environment and metastatic tumors that developed
      were analyzed. A high-throughput modified genomic sequencing PCR (MGS-PCR)
      approach identified the positions of vector integrations in these metastatic
      tumors. OR2A14, FER1L6, TAOK3, MAN1A2, MBNL2, SERBP1, PLEKHA2, SPTAN1, ADAMTS1,
      SLC30A5, ABCC1, SLC7A1 and SLC25A24 were identified as candidate prostate cancer
      (PC) progression genes. TAOK3 and ABCC1 expression in PC patients predicted the
      risk of recurrence after androgen deprivation therapy. Our data shows that
      gammaRV and LV vectors are complementary approaches to identify cancer driver
      genes which may be promising potential biomarkers and therapeutic targets.

PMID- 29643986
TI  - Ajuba receptor mediates the internalization of tumor-secreted GRP78 into
      macrophages through different endocytosis pathways.
AB  - Glucose-regulated protein 78 (GRP78), an ER chaperone, is overexpressed in cancer
      cells. Solid tumor cells can secrete GRP78 that can promote tumor angiogenesis,
      differentiation of bone marrow-derived mesenchymal stem cells, tumor cell
      proliferation and polarization of tumor-associated macrophages. However, the
      mechanism by which GRP78 functions as a tumor promoter either by staying on the
      membrane to stimulate intracellular signals or directly entering into cytosolic
      remains unknown. Here, we reported that an endotoxin-free His-GRP78 protein was
      purified in vitro that simulates original secreted GRP78. Through analyzing GRP78
      concentration in serum samples from 32 colon cancer patients, 40 nM His-GRP78 was
      selected as an optimized dose to treat cells. Biochemical analysis revealed that
      secreted GRP78 was able to enter into RAW264.7 and THP-1 cells directly rather
      than stay on the plasma membrane to transfer signals. Further studies showed that
      GRP78 internalization was endocytosis-dependent, and both phagocytosis and
      clathrin, caveolin-1 and micropinocytosis-mediated endocytosis pathways
      contributed to internalization of secreted GRP78 into cells. Mechanistically,
      Ajuba is able to interact with GRP78. Ablation of Ajuba suppressed the
      internalization of secreted GRP78 into cells, indicating that Ajuba was
      responsible for internalization of secreted GRP78 into RAW264.7. Furthermore, we
      observed that internalized GRP78 could entered into the mitochondrion and
      endoplasmic reticulum, which provided a suitable place and enough time for GRP78
      to function in molecular and cellular processes. Together, these results reveal a
      novel mechanism by which secreted GRP78 internalizes into macrophages in the
      tumor microenvironment, which provides a potential target for drug development.

PMID- 29643982
TI  - Nutrients and Oxidative Stress: Friend or Foe?
AB  - There are different types of nutritionally mediated oxidative stress sources that
      trigger inflammation. Much information indicates that high intakes of
      macronutrients can promote oxidative stress and subsequently contribute to
      inflammation via nuclear factor-kappa B- (NF-kappaB-) mediated cell signaling
      pathways. Dietary carbohydrates, animal-based proteins, and fats are important to
      highlight here because they may contribute to the long-term consequences of
      nutritionally mediated inflammation. Oxidative stress is a central player of
      metabolic ailments associated with high-carbohydrate and animal-based protein
      diets and excessive fat consumption. Obesity has become an epidemic and
      represents the major risk factor for several chronic diseases, including
      diabetes, cardiovascular disease (CVD), and cancer. However, the molecular
      mechanisms of nutritionally mediated oxidative stress are complex and poorly
      understood. Therefore, this review aimed to explore how dietary choices
      exacerbate or dampen the oxidative stress and inflammation. We also discussed the
      implications of oxidative stress in the adipocyte and glucose metabolism and
      obesity-associated noncommunicable diseases (NCDs). Taken together, a better
      understanding of the role of oxidative stress in obesity and the development of
      obesity-related NCDs would provide a useful approach. This is because oxidative
      stress can be mediated by both extrinsic and intrinsic factors, hence providing a
      plausible means for the prevention of metabolic disorders.

PMID- 29643987
TI  - Proteomic analysis defines kinase taxonomies specific for subtypes of breast
      cancer.
AB  - Multiplexed small molecule inhibitors covalently bound to Sepharose beads (MIBs)
      were used to capture functional kinases in luminal, HER2-enriched and triple
      negative (basal-like and claudin-low) breast cancer cell lines and tumors. Kinase
      MIB-binding profiles at baseline without perturbation proteomically distinguished
      the four breast cancer subtypes. Understudied kinases, whose disease associations
      and pharmacology are generally unexplored, were highly represented in MIB-binding
      taxonomies and are integrated into signaling subnetworks with kinases that have
      been previously well characterized in breast cancer. Computationally it was
      possible to define subtypes using profiles of less than 50 of the more than 300
      kinases bound to MIBs that included understudied as well as metabolic and lipid
      kinases. Furthermore, analysis of MIB-binding profiles established potential
      functional annotations for these understudied kinases. Thus, comprehensive MIBs
      based capture of kinases provides a unique proteomics-based method for
      integration of poorly characterized kinases of the understudied kinome into
      functional subnetworks in breast cancer cells and tumors that is not possible
      using genomic strategies. The MIB-binding profiles readily defined subtype
      selective differential adaptive kinome reprogramming in response to targeted
      kinase inhibition, demonstrating how MIB profiles can be used in determining
      dynamic kinome changes that result in subtype selective phenotypic state changes.

PMID- 29643988
TI  - Combination therapy of chitosan, gynostemma, and motherwort alleviates the
      progression of experimental rat chronic renal failure by inhibiting STAT1
      activation.
AB  - This study aimed to investigate the effect of single and combination therapy
      using chitosan (K), gynostemma (J), and motherwort (Y) on an experimental rat
      model of chronic renal failure (CRF) induced by adenine and the underlying
      mechanisms. CRF rats were treated with individual or combinational therapy with
      two or three of these agents. Biochemical indicators showed that the levels of
      blood urea nitrogen, creatinine and uric acid decreased and the levels of albumin
      and hemoglobin increased by single or combination therapy of these drugs. Drug
      treatment also decreased oxidative stress damage of renal tissues in CRF rats.
      Histopathological lesions were attenuated in each drug treatment group by various
      degrees. Additionally, drug treatment affected the expression of extracellular
      matrix (ECM) proteins including plasminogen activator inhibitor 1, collagen I,
      matrix metalloprotease-1, and tissue inhibitor of metalloproteinases 1. In
      particular, the combination therapy of K, J, and Y was superior to the respective
      monotherapy, which supported the prescription of KJY combination. We further
      studied the inhibitory effect of KJY on LPS-induced inflammation in RAW264.7
      macrophages. The results showed that KJY inhibited LPS-induced secretion of
      inflammatory cytokines (Interferon-gamma, Interleukin-1 Beta, chemokine (C-X-C
      motif) ligand 10, cyclooxygenase-2 and Tumor necrosis factor-alpha in RAW264.7
      macrophages. Combination therapy of KJY suppressed the protein expression of
      Cyclooxygenase-2 and inducible nitric oxide synthase in vivo and in vitro.
      Further study indicated that KJY inhibited STAT1 activation by down regulating p
      STAT1 to exert anti-inflammatory effect and improve renal function in rats with
      chronic renal failure.

PMID- 29643989
TI  - The lncRNA H19 positively affects the tumorigenic properties of glioblastoma
      cells and contributes to NKD1 repression through the recruitment of EZH2 on its
      promoter.
AB  - The still largely obscure molecular events in the glioblastoma oncogenesis, a
      primary brain tumor characterized by an inevitably dismal prognosis, impel for
      investigation. The importance of Long noncoding RNAs as regulators of gene
      expression has recently become evident. Among them, H19 has a recognized
      oncogenic role in several types of human tumors and was shown to correlate to
      some oncogenic aspects of glioblastoma cells. Here we, hypothesyze that in
      glioblastoma H19 exerts its function through the interaction with the catalytic
      subunit of the PRC2 complex, EZH2. By employing a factor analysis on a SAGE
      dataset of 12 glioblastoma samples, we show that H19 expression in glioblastoma
      tissues correlates with that of several genes involved in glioblastoma growth and
      progression. H19 knock-down reduces viability, migration and invasiveness of two
      distinct human glioblastoma cell lines. Most importantly, we provide a
      mechanistic perspective about the role of H19 in glioblastoma cells, by showing
      that its expression is inversely linked to that of NKD1, a negative regulator of
      Wnt pathway, suggesting that H19 might regulate NKD1 transcription via EZH2
      induced H3K27 trimethylation of its promoter. Indeed, we showed that H19 binds
      EZH2 in glioblastoma cells, and that EZH2 binding to NKD1 and other promoters is
      impaired by H19 silencing. In this work we describe H19 as part of an epigenetic
      modulation program executed by EZH2, that results in the repression of Nkd1. We
      believe that our results can provide a new piece to the complex puzzle of H19
      function in glioblastoma.

PMID- 29643990
TI  - Systematic characterization of autophagy-related genes during the adipocyte
      differentiation using public-access data.
AB  - Autophagy contributes to reorganizing intracellular components and forming fat
      droplets during the adipocyte differentiation. Here, we systematically describe
      the role of autophagy-related genes and gene sets during the differentiation of
      adipocytes. We used a public dataset from the European Nucleotide Archive from an
      RNA-seq experiment in which 3T3-L1 cells were induced by a differentiation
      induction medium, total RNA was extracted and sequenced at four different time
      points. Raw reads were aligned to the UCSC mouse reference genome (mm10) using
      HISAT2, and aligned reads were summarized at the gene or exon level using HTSeq.
      DESeq2 and DEXSeq were used to model the gene and exon counts and test for
      differential expression and relative exon usage, respectively. After applying the
      appropriate transformation, gene counts were used to perform the gene set and
      pathway enrichment analysis. Data were obtained, processed and annotated using R
      and Bioconductor. Several autophagy-related genes and autophagy gene sets, as
      defined in the Gene Ontology, were actively regulated during the course of the
      adipocyte differentiation. We further characterized these gene sets by clustering
      their members to a few distinct temporal profiles. Other potential functionally
      related genes were identified using a machine learning procedure. In summary, we
      characterized the autophagy gene sets and their members to biologically
      meaningful groups and elected a number of genes to be functionally related based
      on their expression patterns, suggesting that autophagy plays a critical role in
      removal of some intracellular components and supply of energy sources for lipid
      biogenesis during adipogenesis.

PMID- 29643991
TI  - Serum levels of soluble CD163 and CXCL5 may be predictive markers for immune
      related adverse events in patients with advanced melanoma treated with nivolumab:
      a pilot study.
AB  - Antibodies against PD-1, such as nivolumab and pembrolizumab, are widely used in
      the treatment of various cancers including advanced melanoma. The anti-PD-1 Ab
      significantly prolongs survival in patients with metastatic melanoma, and its
      administration in combination with local or systemic therapy may also lead to
      improved outcomes. Although anti-PD-1 Ab-based combined therapy might be
      effective for the treatment of advanced melanoma, the associated risk of irAEs is
      an important consideration. Therefore, being able to predict irAEs is of great
      interest to oncologists. The purpose of this study was to evaluate the value of
      using serum levels of sCD163 and CXCL5 to predict irAEs in patients with advanced
      melanoma who were administered nivolumab. To this end, we analyzed these serum
      levels in 46 cases of advanced melanoma treated with nivolumab. In addition, the
      tumor stroma was evaluated by immunohistochemistry and immunofluorescence. We
      measured the serum levels of sCD163 and CXCL5 on day 0 (immediately before
      nivolumab administration) and day 42. The serum absolute levels of sCD163 were
      significantly increased in patients who developed AEs (p = 0.0018). Although
      there was no significant difference in serum levels of CXCL5, the absolute value
      of CXCL5 could at least be a supportive marker for the increased absolute levels
      of serum sCD163. This study suggests that sCD163 and CXCL5 may serve as possible
      prognostic biomarkers for irAEs in patients with advanced melanoma treated with
      nivolumab.

PMID- 29643992
TI  - Description of organ-specific phenotype, and functional characteristics of tissue
      resident lymphocytes from liver transplantation donor and research on immune
      tolerance mechanism of liver.
AB  - Aim: Prior to transplantation, Donation after Cardiac Death (DCD) liver
      transplantation livers are perfused with preservation solution. Therefore, this
      provides an abundant source of human liver lymphocytes, as well as mesenteric
      lymph node and spleen for the study of lymphocyte subset diversity in the
      peripheral blood, lymph node, spleen and liver. Methods: Lymphocyte subsets were
      isolated and purified from peripheral blood, lymph node, spleen and liver
      perfusion, the phenotypic and functional analysis of the tissue resident
      lymphocyte were performed by flow cytometry. Results: In a direct comparison
      between blood, liver, lymph node and spleen cells from liver transplantation
      donors, the abundance of natural killer (NK) cells, CD3+CD56+NKT (NT) cells and
      CD8+ T cells in intrahapatic lymphocytes (IHL) did not match what was present in
      peripheral blood and other peripheral lymphoid organs. The activation state of
      peripheral blood-derived lymphocytes was significantly different from lymph node
      , spleen- and liver-derived cells. Intriguingly, NK cells, CD4+ T cells, and CD8+
      T cells from liver perfusion display more suppressive characteristics, that is,
      express and produce more anti-inflammatory cytokine interleukin (IL)-10, less
      inflammatory cytokine interferon (INF)-gamma. Conclusion: Our findings imply that
      different tissues entail resident lymphocyte subsets with a distinct phenotype
      and function considering the organ is well vascularized, particularly in liver.
      It is better to understand the mechanism of liver immune tolerance.

PMID- 29643993
TI  - Relationship between the agonist activity of synthetic ligands of TRAIL-R2 and
      their cell surface binding modes.
AB  - Tumor Necrosis Factor Receptor Apoptosis Inducing Ligand (TRAIL) appears as an
      interesting candidate for targeted cancer therapy as it induces apoptosis in
      cancer cells without toxicity to normal cells. TRAIL elicits apoptosis through
      agonist death receptor TRAIL-R1 and TRAIL-R2 engagement. Nevertheless,
      recombinant soluble TRAIL and monoclonal antibodies against these receptors
      demonstrated insufficient efficacy in clinical trials. This may be explained by
      the cell-type dependency of the apoptotic response, itself influenced by the
      effect on ligand binding mode of factors such as the level of receptor
      oligomerization or glycosylation. To investigate the relation between binding
      mode and signaling, we used previously described synthetic divalent and
      monovalent peptides specific for TRAIL-R2. We measured their pro-apoptotic
      activity on three cancer cell lines sensitive to rhTRAIL induced-apoptosis and
      monitored their cell-surface binding kinetics. The two divalent peptides bound
      with strong affinity to TRAIL-R2 expressed on B lymphoma BJAB cells and induced a
      high degree of apoptosis. By contrast, the same peptides bound weakly to TRAIL-R2
      expressed at the surface of the human colon cancer HCT116 or T lymphoma Jurkat
      cell lines and did not induce their apoptosis. Cross-linking experiments suggest
      that these differences could be afforded by variations in the TRAIL-R2
      oligomerization state at cell surface before ligand addition. Moreover divalent
      peptides showed a different efficiency in BJAB apoptosis induction, and kinetic
      distribution analysis of the BJAB binding curves suggested subtle differences in
      binding mechanisms. Thus our data support a relation between the cell-surface
      binding mode of the peptides and their pro-apoptotic activity. In this case the
      precise characterization of ligand binding to the surface of living cells would
      be predictive of the therapeutic potential of TRAIL-R2 synthetic ligands prior to
      clinical trials.

PMID- 29643994
TI  - Grape seed procyanidin extract against lung cancer: the role of microrna-106b,
      bioavailability, and bioactivity.
AB  - MiR-106b is an oncomir and a potential target for anti-cancer therapy. We
      hypothesize that grape seed procyanidin extract (GSE) exerts antineoplastic
      effects on lung cancer through modulations of miR-106b and its downstream target.
      We found that GSE significantly down-regulated miR-106b in a variety of lung
      neoplastic cells and increased cyclin-dependent kinase inhibitor 1A (CDKN1A) mRNA
      and protein (p21) levels. Transfection of miR-106b mimics reversed the up
      regulations of CDKN1A mRNA and p21, abrogated the GSE induced anti-proliferative
      and anti-invasive properties in lung cancer cells. Oral gavage of leucoselect
      phytosome (LP), a standardized GSE to athymic nude mice down-regulated MIR106B
      mRNA and miR-106b expressions, and increased CDKN1A mRNA expression in tumor
      xenografts, correlating to significant reduction of tumor growth. To assess
      bioavailability, GSE and metabolites in plasma levels, between 60-90 minutes
      after gavage of LP were measured by LC/MS at treatment week 4 and 8. A novel
      bioactivity assay was also developed using lung homogenates from treated mice co
      cultured with human lung cancer cells. LP-treated mouse lung homogenates
      significantly reduced proliferations of various lung cancer cells. Our findings
      reveal novel antineoplastic mechanisms by GSE, further define the
      pharmacokinetics and pharmacodynamics of LP, and support the continued
      investigation of LP against lung cancer.

PMID- 29643995
TI  - Treatment of oral cancer using magnetized paclitaxel.
AB  - N,N'-Bis(salicylidene)ethylenediamine iron (Fe(Salen)) is an anti-cancer agent
      with intrinsic magnetic property. Here, we covalently linked Fe(Salen) to
      paclitaxel (PTX), a widely used anti-cancer drug, to obtain a magnetized
      paclitaxel conjugate (M-PTX), which exhibited magnetic characteristics for magnet
      guided drug delivery and MRI visualization. M-PTX increased apoptosis and G2/M
      arrest of cultured human oral cancer cell lines in the same manner as PTX.
      Furthermore, marked contrast intensity was obtained in magnetic resonance imaging
      (MRI) of M-PTX. In a mouse oral cancer model, a permanent magnet placed on the
      body surface adjacent to the tumor resulted in distinct accumulation of M-PTX,
      and the anti-cancer effect was greater than that of M-PTX without the magnet. We
      believe that this strategy may improve future cancer chemotherapy by providing
      conventional anti-cancer drugs with novel functionalities such as magnet-guided
      drug delivery or MRI-based visualization/quantitation of drug distribution.

PMID- 29643996
TI  - Selective lysis of breast carcinomas by simultaneous stimulation of sodium
      channels and blockade of sodium pumps.
AB  - Sodium influx through voltage-gated sodium channels (VGSCs) coupled with balanced
      removal of sodium ions via Na+, K+-ATPase is a major determinant of cellular
      homeostasis and intracellular ionic concentration. Interestingly, many metastatic
      carcinomas express high levels of these channels. We hypothesized that if excess
      VGSCs are activated and Na+, K+-ATPase is simultaneously blocked, the
      intracellular Na+ concentration should increase, resulting in water movement into
      the cell, causing swelling and lytic cell death. MDA-MB-231 breast cancer cells
      over-express VGSCs by 7-fold. To test our hypothesis, we treated these cells in
      vitro with the Na+, K+-ATPase blocker, ouabain, and then stimulated with a
      sublethal electric current. For in vivo histologic and survival studies, MDA-MB
      231 xenografts were established in Nu/J mice. Mice injected with saline or
      ouabain were electrically stimulated with trains of 10 msec 10V DC pulses. Within
      seconds to minutes, the cells swelled and lysed. MCF-10a cells, which express
      normal VGSCs levels, were unaffected by this treatment. Cells from the weakly
      malignant cell line, MCF-7, which express 3-fold greater VGSCs than MCF-10a
      cells, displayed an intermediate time-to-lysis. The rate of lysis correlated
      directly with the degree of sodium channel expression and malignancy. We also
      demonstrated efficacy in cell lines from prostate, colon and lung carcinomas.
      Treated MDA-MB-231 xenografts showed 60-80% cell death. In survival studies, TOL
      treated mice showed significantly slower tumor growth vs. controls. These results
      are evidence that this "targeted osmotic lysis" represents a novel method for
      selectively killing cancer cells and warrants further investigation as a
      potential treatment for advanced and end-stage breast cancer.

PMID- 29643997
TI  - New antimicrobial peptide kills drug-resistant pathogens without detectable
      resistance.
AB  - Clavaspirin peptide (CSP) is derived from the pharyngeal tissues of the tunicate
      Styela clava. The 23-amino acid peptide is histidine-rich and amidated at the N
      terminus. CSP possesses low antimicrobial and high hemolytic activity at pH 7.4.
      Therefore, we designed 4 CSP analogs with substituted hydrophobic amino acids to
      reduce hydrophobic amino acid interactions. These modifications reduced the
      aggregation and cytotoxicity of the analogs at pH 7.4. The analogs also showed
      potent antimicrobial activity by accumulating on bacterial cell surfaces and
      inducing the lytic mechanism against gram-negative and gram-positive cells at pH
      5.5 and 7.4. Moreover, exposure to the CSP-4 analog for up to 29 passages did not
      induce drug resistance in Staphylococcus aureus. Application of CSP-4 to inflamed
      skin of hairless mice infected with drug-resistant S. aureus (DRSA) significantly
      reduced skin infections without damaging dermal collagen or elastin. Topically
      applied CSP-4 penetrated 25-40 um in the dermis within 30 min, reducing the
      levels of Toll-like receptor-2, nuclear factor kappa B (NF-kappaB), and the pro
      inflammatory cytokines tumor necrosis factor- alpha (TNF-alpha) and interleukin
      1beta (IL-1 beta). These results suggest that CSP-4 could be a promising topical
      antimicrobial agent for skin diseases caused by DRSA such as S. aureus CCARM
      0027.

PMID- 29643999
TI  - Sympatho-adrenergic activation by endurance exercise: Effect on metanephrines
      spillover and its role in predicting athlete's performance.
AB  - Background: The sympatho-adrenergic activation during exercise is implicated in
      many cardiovascular respiratory and metabolic adaptations which have been thought
      to partially explain the different levels of performance observed between trained
      and untrained subjects. To date, no evidence exists about the association between
      competition performance and markers of "acute stress response". We designed this
      study to investigate; (i) the acute sympatho-adrenergic activation during
      endurance exercise in recreational runners by measuring plasma levels of free
      metanephrine (MN) and normethanephrine (NMN) before and after a half-marathon
      run; (ii) the association between the metanephrines levels and the running time.
      Methods: 26 amateur runners (15 males, 11 females) aged 30 to 63 years were
      enrolled. The quantification of MN and NMN was performed by LC-MS/MS.
      Anthropometric ergonomic and routine laboratory data were recorded. Statistical
      analyses included paired T-test, univariate and multivariate regressions.
      Results: The post-run values of MN and NMN displayed a nearly 3.5 and 7 fold
      increase respectively compared to the baseline values (p < 0.0001 for both). NMN
      pre-run values and pre/post run delta values showed a significant direct and
      inverse association (p = 0.021 and p = 0.033, respectively) with running
      performance. No correlations were found for MN values. Conclusion: NMN is a
      reliable marker of sympatho-adrenergic activation by exercise and can predict
      endurance performance in the individual athlete. Adaptation phenomenon occurring
      not only in the adrenal medulla might represent the biological mechanism
      underlying this association. Further studies on sympatho-adrenergic activation,
      competition performance and training status should contemplate the measurement of
      these metabolites instead of their unstable precursors.

PMID- 29643998
TI  - Deletion of sphingosine kinase 1 inhibits liver tumorigenesis in
      diethylnitrosamine-treated mice.
AB  - Primary liver cancer is the 3rd leading cause of cancer deaths worldwide with
      very few effective treatments. Sphingosine kinase 1 (SphK1), a key regulator of
      sphingolipid metabolites, is over-expressed in human hepatocellular carcinoma
      (HCC) and our previous studies have shown that SphK1 is important in liver
      injury. We aimed to explore the role of SphK1 specifically in liver tumorigenesis
      using the SphK1 knockout (SphK1-/-) mouse. SphK1 deletion significantly reduced
      the number and the size of DEN-induced liver cancers in mice. Mechanistically,
      fewer proliferating but more apoptotic and senescent cells were detected in SphK1
      deficient tumors compared to WT tumors. There was an increase in sphingosine
      rather than a decrease in sphingosine 1-phosphate (S1P) in SphK1 deficient
      tumors. Furthermore, the STAT3-S1PR pathway that has been reported previously to
      mediate the effect of SphK1 on colorectal cancers was not altered by SphK1
      deletion in liver cancer. Instead, c-Myc protein expression was down-regulated by
      SphK1 deletion. In conclusion, this is the first in vivo evidence that SphK1
      contributes to hepatocarcinogenesis. However, the downstream signaling pathways
      impacting on the development of HCC via SphK1 are organ specific providing
      further evidence that simply transferring known oncogenic molecular pathway
      targeting into HCC is not always valid.

PMID- 29644000
TI  - CDK4/6 inhibition as maintenance and combination therapy for high grade serous
      ovarian cancer.
AB  - High grade serous ovarian cancer (HGSOC) is a disease with a high relapse rate
      and poor overall survival despite good initial responses to platinum-based
      therapy. Cell cycle inhibition with targeted CDK4/6 inhibitors is a new
      therapeutic approach showing promise as a maintenance therapy in cancer. As
      multiple genes in the CDK4/6 pathway are commonly mutated or dysregulated in
      ovarian cancer, we evaluated the efficacy of the CDK4/6 inhibitor Ribociclib
      alone, in combination with chemotherapy, and as maintenance therapy in several
      models of HGSOC. Ribociclib restricted cellular proliferation in multiple ovarian
      cancer cell lines. Restricted proliferation was associated with a pseudo
      senescent cellular phenotype; Ribociclib-treated cells expressed markers of
      senescence, but could rapidly re-enter the cell cycle with discontinuation of
      therapy. Surprisingly, concurrent Ribociclib and cisplatin therapy followed by
      Ribociclib maintenance was synergistic. Evaluation of the cell cycle suggested
      that Ribociclib may also act at the G2/M check point via dephosphorylation of ATR
      and CHK1. Consistent with this mechanism, Ribociclib demonstrated clear activity
      in both platinum-resistant and platinum-sensitive tumor models in vivo. This work
      supports clinical trials using Ribociclib in combination with cisplatin and as a
      maintenance therapy in ovarian cancer.

PMID- 29644001
TI  - BAG3 promotes tumour cell proliferation by regulating EGFR signal transduction
      pathways in triple negative breast cancer.
AB  - Triple-negative breast cancer (TNBC), is a heterogeneous disease characterised by
      absence of expression of the estrogen receptor (ER), progesterone receptor (PR)
      and lack of amplification of human epidermal growth factor receptor 2 (HER2).
      TNBC patients can exhibit poor prognosis and high recurrence stages despite early
      response to chemotherapy treatment. In this study, we identified a pro-survival
      signalling protein BCL2- associated athanogene 3 (BAG3) to be highly expressed in
      a subset of TNBC cell lines and tumour tissues. High mRNA expression of BAG3 in
      TNBC patient cohorts significantly associated with a lower recurrence free
      survival. The epidermal growth factor receptor (EGFR) is amplified in TNBC and
      EGFR signalling dynamics impinge on cancer cell survival and disease recurrence.
      We found a correlation between BAG3 and EGFR expression in TNBC cell lines and
      determined that BAG3 can regulate tumour cell proliferation, migration and
      invasion in EGFR expressing TNBC cells lines. We identified an interaction
      between BAG3 and components of the EGFR signalling networks using mass
      spectrometry. Furthermore, BAG3 contributed to regulation of proliferation in
      TNBC cell lines by reducing the activation of components of the PI3K/AKT and
      FAK/Src signalling subnetworks. Finally, we found that combined targeting of BAG3
      and EGFR was more effective than inhibition of EGFR with Cetuximab alone in TNBC
      cell lines. This study demonstrates a role for BAG3 in regulation of distinct
      EGFR modules and highlights the potential of BAG3 as a therapeutic target in
      TNBC.

PMID- 29644002
TI  - Loss of neutrophil polarization in colon carcinoma liver metastases of mice with
      an inducible, liver-specific IGF-I deficiency.
AB  - The growth of cancer metastases in the liver depends on a permissive interaction
      with the hepatic microenvironment and neutrophils can contribute to this
      interaction, either positively or negatively, depending on their phenotype. Here
      we investigated the role of IGF-I in the control of the tumor microenvironment in
      the liver, using mice with a conditional, liver-specific, IGF-I deficiency (iLID)
      induced by a single tamoxifen injection. In mice that had a sustained (3 weeks)
      IGF-I deficiency prior to the intrasplenic/portal inoculation of colon carcinoma
      MC-38 cells, we observed an increase in neutrophil accumulation in the liver
      relative to controls. However, unlike controls, these neutrophils did not acquire
      the (anti-inflammatory) tumor-promoting phenotype, as evidenced by retention of
      high ICAM-1 expression and nitric oxide production and low CXCR4, CCL5, and VEGF
      expression and arginase production, all characteristic of the (pro-inflammatory)
      phenotype. This coincided with an increase in apoptotic tumor cells and reduced
      metastasis. Neutrophils isolated from these mice also had reduced IGF-IR
      expression levels. These changes were not observed in iLID mice with a short-term
      (2 days) IGF-I depletion, despite a 70% reduction in their circulating IGF-I
      levels, indicating that a sustained IGF-I deficiency was necessary to alter the
      neutrophil phenotype. Similar results were obtained with the highly metastatic
      Lewis lung carcinoma subline H-59 cells and in mice injected with an IGF-Trap
      that blocks IGF-IR signaling by reducing ligand bioavailability. Our results
      implicate the IGF axis in neutrophil polarization and the induction of a pro
      metastatic microenvironment in the liver.

PMID- 29644003
TI  - Overexpression of PLOD3 promotes tumor progression and poor prognosis in gliomas.
AB  - High-grade gliomas are the most threatening brain tumors due to aggressive
      proliferation and poor prognosis. Thus, utilizing genetic glioma biomarkers to
      forecast prognosis and guide clinical management is crucial. Procollagen-lysine,
      2-oxoglutarate 5-dioxygenase 3 (PLOD3) modulates cancer progression and
      metastasis. However, its detailed function in cancer remains largely
      uninvestigated. PLOD3 expression was evaluated with real-time PCR in glioblastoma
      (GBM) cell lines and by Gene Expression Omnibus dataset analysis and
      immunohistochemistry of glioma tissues. We investigated the clinical use of PLOD3
      for determining glioma prognosis. The biological roles of PLOD3 in proliferation,
      migration and invasion of GBM cells were studied both in vitro with wound-healing
      and transwell assays and in vivo using an orthotopic xenograft mouse model.
      Hypoxia and western blotting were applied to discover the molecular mechanisms
      underlying PLOD3 functions. PLOD3 mRNA and protein expression were upregulated in
      glioma tissues compared to normal brain tissues. PLOD3 overexpression was
      correlated with negative survival in glioma patients. PLOD3 silencing suppressed
      cell proliferation and induced G1 phase arrest through p53-independent regulation
      of the p21 pathway. Inhibition of PLOD3 in glioma cells decreased VEGF
      expression, migration and invasion by downregulating mesenchymal markers,
      including Snail and Twist. Notably, knockdown of PLOD3 inhibited HIF-1alpha
      accumulation via the ERK signaling pathway under hypoxia. Taken together, these
      discoveries reveal that PLOD3 is a potential therapeutic target in human gliomas.

PMID- 29644004
TI  - IL-8 associates with a pro-angiogenic and mesenchymal subtype in glioblastoma.
AB  - Glioblastoma (GBM) is a highly aggressive brain tumor characterized by a high
      rate of vascularization. However, therapeutic targeting of the vasculature
      through anti-vascular endothelial growth factor (VEGF) treatment has been
      disappointing, for which Angiopoietin-2 (Ang-2) upregulation has partly been held
      accountable. In this study we therefore explored the interplay of Ang-2 and VEGFA
      and their effect on angiogenesis in GBM, especially in the context of molecular
      subclasses. In a large patient cohort we identified that especially combined high
      expression of Ang-2 and VEGFA predicted poor overall survival of GBM patients.
      The high expression of both factors was also associated with increased IL-8
      expression in GBM tissues, but in vitro stimulation with Ang-2 and/or VEGFA did
      not indicate tumor or endothelial cell-specific IL-8 responses. Glioblastoma stem
      cells (GSCs) of the mesenchymal (MES) subtype showed dramatically higher
      expression of IL8 when compared to proneural (PN) GSCs. Secreted IL-8 derived
      from MES GSCs induced endothelial proliferation and tube formation, and the MES
      GBMs had increased counts of proliferating endothelial cells. Our results
      highlight a critical pro-angiogenic role of IL-8 in MES GBMs.

PMID- 29644005
TI  - Radiofrequency assisted pancreaticoduodenectomy for palliative surgical resection
      of locally advanced pancreatic adenocarcinoma.
AB  - Background: Despite careful patient selection and preoperative investigations
      curative resection rate (R0) in pancreaticoduodenectomy ranges from 15% to 87%.
      Here we describe a new palliative approach for pancreaticoduodenectomy using a
      radiofrequency energy device to ablate tumor in situ in patients undergoing R1/R2
      resections for locally advanced pancreatic ductal adenocarcinoma where vascular
      reconstruction was not feasible. Results: There was neither postoperative
      mortality nor significant morbidity. Each time the ablation lasted less than 15
      minutes. Following radiofrequency ablation it was observed that the tumor remnant
      attached to the vessel had shrunk significantly. In four patients this allowed
      easier separation and dissection of the ablated tumor from the adherent vessel
      leading to R1 resection. In the other two patients, the ablated tumor did not
      separate from vessel due to true tumor invasion and patients had an R2 resection.
      The ablated remnant part of the tumor was left in situ. Conclusion: Whenever
      pancreaticoduodenectomy with R0 resection cannot be achieved, this new palliative
      procedure could be considered in order to facilitate resection and enable maximum
      destruction in remnant tumors. Method: Six patients with suspected tumor
      infiltration and where vascular reconstruction was not warranted underwent
      radiofrequency-assisted pancreaticoduodenectomy for locally advanced pancreatic
      ductal adenocarcinoma. Radiofrequency was applied across the tumor vertically 5
      10 mm from the edge of the mesenteric and portal veins. Following ablation, the
      duodenum and the head of pancreas were removed after knife excision along the
      ablated line. The remaining ablated tissue was left in situ attached to the
      vessel.

PMID- 29644006
TI  - The long non-coding RNA HOTAIR is transcriptionally activated by HOXA9 and is an
      independent prognostic marker in patients with malignant glioma.
AB  - The lncRNA HOTAIR has been implicated in several human cancers. Here, we
      evaluated the molecular alterations and upstream regulatory mechanisms of HOTAIR
      in glioma, the most common primary brain tumors, and its clinical relevance.
      HOTAIR gene expression, methylation, copy-number and prognostic value were
      investigated in human gliomas integrating data from online datasets and our
      cohorts. High levels of HOTAIR were associated with higher grades of glioma,
      particularly IDH wild-type cases. Mechanistically, HOTAIR was overexpressed in a
      gene dosage-independent manner, while DNA methylation levels of particular CpGs
      in HOTAIR locus were associated with HOTAIR expression levels in GBM clinical
      specimens and cell lines. Concordantly, the demethylating agent 5-Aza-2'
      deoxycytidine affected HOTAIR transcriptional levels in a cell line-dependent
      manner. Importantly, HOTAIR was frequently co-expressed with HOXA9 in high-grade
      gliomas from TCGA, Oncomine, and our Portuguese and French datasets. Integrated
      in silico analyses, chromatin immunoprecipitation, and qPCR data showed that
      HOXA9 binds directly to the promoter of HOTAIR. Clinically, GBM patients with
      high HOTAIR expression had a significantly reduced overall survival,
      independently of other prognostic variables. In summary, this work reveals HOXA9
      as a novel direct regulator of HOTAIR, and establishes HOTAIR as an independent
      prognostic marker, providing new therapeutic opportunities to treat this highly
      aggressive cancer.

PMID- 29644007
TI  - Impact of adjuvant hormonotherapy on radiation-induced breast fibrosis according
      to the individual radiosensitivity: results of a multicenter prospective French
      trial.
AB  - Background: To evaluate risk of severe breast fibrosis occurrence in patients
      treated by breast-conserving surgery, adjuvant radiotherapy and hormonotherapy
      (HT) according to individual radiosensitivity (RILA assay). Results: HT- and
      RILAhigh were the two independent factors associated with improved breast
      fibrosis free survival (BFFS). BFFS rate at 36 months was lower in patients with
      RILAlow and HT+ than in patients with RILAhigh and HT- (75.8% and 100%,
      respectively; p = 0.004, hazard ratio 5.84 [95% confidence interval (CI) 1.8
      19.1]). Conversely, BFFS at 36 months was comparable in patients with RILAhigh
      and HT+ and in patients with RILAlow and HT- (89.8% and 93.5%, respectively; p =
      0.39, hazard ratio 1.7 [95% CI 0.51-5.65]), showing that these two parameters
      influenced independently the occurrence of severe breast fibrosis. BFFS rate was
      not affected by the HT type (tamoxifen or aromatase inhibitor) and timing
      (concomitant or sequential with radiotherapy). Conclusions: HT and RILA score
      independently influenced BFFS rate at 36 months. Patients with RILAhigh and HT-
      presented an excellent BFFS at 36 months (100%). Materials and methods: Breast
      Fibrosis-Free Survival (BFFS) rate was assessed relative to RILA categories and
      to adjuvant HT use (HT+ and HT-, respectively) in a prospective multicentre study
      (NCT00893035) which enrolled 502 breast cancer patients (456 evaluable patients).
      Breast fibrosis was recorded according to CTCAE v3.0 grading scale; RILA score
      was defined according to two categories (<12%: RILAlow; >=12%: RILAhigh).

PMID- 29644008
TI  - Calcium-sensing receptor (CaSR) promotes development of bone metastasis in renal
      cell carcinoma.
AB  - Bone metastasis is an important prognostic factor in renal cell carcinoma (RCC).
      The calcium-sensing receptor (CaSR) has been associated with bone metastasis in
      several different malignancies. We analyzed the impact of CaSR in bone metastasis
      in RCC in vitro and in vivo. The RCC cell line 786-O was stably transfected with
      the CaSR gene and treated with calcium alone or in combination with the CaSR
      antagonist NPS2143. Afterwards migration, adhesion, proliferation and prominent
      signaling molecules were analyzed. Calcium treated CaSR-transfected 768-O cells
      showed an increased adhesion to endothelial cells and the extracellular matrix
      components fibronectin and collagen I, but not to collagen IV. The chemotactic
      cell migration and proliferation was also induced by calcium. The activity of
      SHC, AKT, ERK, P90RSK and JNK were enhanced after calcium treatment of CaSR
      transfected cells. These effects were abolished by NPS2143. Development of bone
      metastasis was evaluated in vivo in a mouse model. Intracardiac injection of CaSR
      transfected 768-O cells showed an increased rate of bone metastasis. The results
      indicate CaSR as an important component in the mechanism of bone metastasis in
      RCC. Therefore, targeting CaSR might be beneficial in patients with bone
      metastatic RCC with a high CaSR expression.

PMID- 29644009
TI  - Pomalidomide enhanced gemcitabine and nab-paclitaxel on pancreatic cancer both in
      vitro and in vivo.
AB  - Background: Chemotherapy with gemcitabine and nab-paclitaxel (gemcitabine/nab
      paclitaxel) is recommended for unresectable pancreatic cancer. However, the
      therapeutic efficacy is attenuated by the antitumor agent-induced activation of
      nuclear factor-kappaB (NF-kappaB). Thalidomide inhibits NF-kappaB activation,
      therefore, we hypothesized that pomalidomide, a third-generation IMiD, would also
      inhibit NF-kappaB activation and enhance the antitumor effects of gemcitabine/nab
      paclitaxel. Methods: In vitro, we assessed NF-kappaB activity and apoptosis in
      response to pomalidomide alone, gemcitabine/nab-paclitaxel, or combination of
      pomalidomide and gemcitabine/nab-paclitaxel in human pancreatic cancer cell lines
      (PANC-1 and MIA PaCa-2). In vivo, we established orthotopic model and the animals
      were treated with oral pomalidomide and injection of gemcitabine/nab-paclitaxel.
      Results: In pomalidomide and gemcitabine/nab-paclitaxel group, gemcitabine/nab
      paclitaxel-induced NF-kappaB activation was inhibited and apoptosis was enhanced
      in comparison with those in the other groups both in vitro and in vivo.
      Especially, this study revealed for the first time that pomalidomide enhances p53
      on pancreatic cancer cells. The tumor growth in the pomalidomide and
      gemcitabine/nab-paclitaxel group was significantly slower than that in the
      gemcitabine/nab-paclitaxel group. Moreover, pomalidomide induced G0/G1 cell cycle
      arrest and suppressed angiogenesis. Conclusions: Pomalidomide enhanced the
      antitumor effect of gemcitabine/nab-paclitaxel by inhibition of NF-kappaB
      activation. This combination regimen would be a novel strategy for treating
      pancreatic cancer.

PMID- 29644011
TI  - Modeling multiple time series annotations as noisy distortions of the ground
      truth: An Expectation-Maximization approach.
AB  - Studies of time-continuous human behavioral phenomena often rely on ratings from
      multiple annotators. Since the ground truth of the target construct is often
      latent, the standard practice is to use ad-hoc metrics (such as averaging
      annotator ratings). Despite being easy to compute, such metrics may not provide
      accurate representations of the underlying construct. In this paper, we present a
      novel method for modeling multiple time series annotations over a continuous
      variable that computes the ground truth by modeling annotator specific
      distortions. We condition the ground truth on a set of features extracted from
      the data and further assume that the annotators provide their ratings as
      modification of the ground truth, with each annotator having specific distortion
      tendencies. We train the model using an Expectation-Maximization based algorithm
      and evaluate it on a study involving natural interaction between a child and a
      psychologist, to predict confidence ratings of the children's smiles. We compare
      and analyze the model against two baselines where: (i) the ground truth in
      considered to be framewise mean of ratings from various annotators and, (ii) each
      annotator is assumed to bear a distinct time delay in annotation and their
      annotations are aligned before computing the framewise mean.

PMID- 29644012
TI  - Abundance, Fishing Season and Management Strategy for Blue Swimming Crab
      (Portunus pelagicus) in Pangkajene Kepulauan, South Sulawesi, Indonesia.
AB  - In order to manage blue swimming crabs in Pangkajene Kepulauan, management
      measures are required. Since the environment which affects the abundance of the
      blue swimming crab varies seasonally, it is necessary to take into account the
      seasonal nature with the aim of developing a management strategy. The objectives
      of this study are to define the abundance of and fishing season of blue swimming
      crabs in the Pangkajene Kepulauan waters, South Sulawesi, Indonesia. The fishing
      season was analysed using seasonal index analysis, while fish abundance was
      analysed by means of Equilibrium-Schaefer. The result of this study demonstrated
      that fishermen allocate their fishing gear all year, although the fish catch is
      seasonal. Based on analysis of the result, the fishing season for the blue
      swimming crabs is short. The peak fishing season starts in May and finishes in
      June. However, in order to enable their families to earn a living, fishermen
      operated their fishing gear throughout the year. As a result, both catch landing
      and effort were close to maximum sustainable yield (MSY). In order to reduce
      fishing pressure, it is necessary to reduce fishing gear and have a seasonal
      arrangement regarding fishing gear allocation.

PMID- 29644010
TI  - Value-based genomics.
AB  - Advancements in next-generation sequencing have greatly enhanced the development
      of biomarker-driven cancer therapies. The affordability and availability of next
      generation sequencers have allowed for the commercialization of next-generation
      sequencing platforms that have found widespread use for clinical-decision making
      and research purposes. Despite the greater availability of tumor molecular
      profiling by next-generation sequencing at our doorsteps, the achievement of
      value-based care, or improving patient outcomes while reducing overall costs or
      risks, in the era of precision oncology remains a looming challenge. In this
      review, we highlight available data through a pre-established and conceptualized
      framework for evaluating value-based medicine to assess the cost (efficiency),
      clinical benefit (effectiveness), and toxicity (safety) of genomic profiling in
      cancer care. We also provide perspectives on future directions of next-generation
      sequencing from targeted panels to whole-exome or whole-genome sequencing and
      describe potential strategies needed to attain value-based genomics.

PMID- 29644013
TI  - Effect of Functionalised and Non-Functionalised Carbon Nanotubes-Urea Fertilizer
      on the Growth of Paddy.
AB  - The roles of multi-walled carbon nanotubes (MWNTs) and functionalised multiwalled
      carbon nanotubes (fMWNTs) in enhancing the efficacy of urea fertilizer (UF) as
      plant nutrition for local MR219 paddy variety was investigated. The MWNTs and
      fMWNTs were grafted onto UF to produce UF-MWNTs fertilizer with three different
      conditions, coded as FMU1 (0.6 wt. % fMWNTs), FMU2 (0.1 wt. % fMWNTs) and MU (0.6
      wt. % MWNTs. The batches of MR219 paddy were systematically grown in accordance
      to the general practice performed by the Malaysian Agricultural Research and
      Development Institute (MARDI). The procedure was conducted using a pot under
      exposure to natural light at three different fertilization times; after a certain
      number of days of sowing (DAS) at 14, 35 and 55 days. Interestingly, it was found
      that the crop growth of plants treated with FMU1 and FMU2 significantly increased
      by 22.6% and 38.5% compared to plants with MU addition. Also, paddy treated with
      FMU1 produced 21.4% higher number of panicles and 35% more grain yield than MU
      while paddy treated with FMU2 gave 28.6% more number of panicles and 36% higher
      grain yield than MU, which implies the advantage of fMWNTs over MWNTs to be
      combined with UF as plant nutrition. The chemical composition and morphology of
      UF-MWNTs fertilizers which is further characterised by FTiR and FESEM confirmed
      the successful and homogeneous grafting of UF onto the fMWNTs.

PMID- 29644014
TI  - Genome Organization of Escherichia Phage YD-2008.s: A New Entry to Siphoviridae
      Family.
AB  - Malaysia is one of the countries that are loaded with mega biodiversity which
      includes microbial communities. Phages constitute the major component in the
      microbial communities and yet the numbers of discovered phages are just a minute
      fraction of its population in the biosphere. Taking into account of a huge
      numbers of waiting to be discovered phages, a new bacteriophage designated as
      Escherichia phage YD-2008.s was successfully isolated using Escherichia coli ATCC
      11303 as the host. Phage YD-2008.s poses icosahedral head measured at 57nm in
      diameter with a long non-contractile flexible tail measured at 107nm; proving the
      phage as one of the members of Siphoviridae family under the order of
      Caudovirales. Genomic sequence analyses revealed phage YD-2008.s genome as linear
      dsDNA of 44,613 base pairs with 54.6% G+C content. Sixty-two open reading frames
      (ORFs) were identified on phage YD-2008.s full genome, using bioinformatics
      annotation software; Rapid Annotation using Subsystem Technology (RAST). Among
      the ORFs, twenty-eight of them code for functional proteins. Thirty two are
      classified as hypothetical proteins and there are two unidentified proteins. Even
      though majority of the coded putative proteins have high amino acids similarities
      to phages from the genus Hk578likevirus of the Siphoviridae family, yet phage YD
      2008.s stands with its' own distinctiveness. Therefore, this is another new
      finding to Siphoviridae family as well as to the growing list of viruses in
      International Committee on Taxonomy of Viruses (ICTV) database.

PMID- 29644015
TI  - Diversity of Bats in Contrasting Habitats of Hulu Terengganu Dipterocarp Forest
      and Setiu Wetland BRIS Forest with a Note on Preliminary Study of Vertical
      Stratification of Pteropodid Bats.
AB  - A study of the bat diversity was conducted in Hulu Terengganu dipterocarp forest
      and Setiu Wetland Beach Ridges Interspersed with Swales (BRIS) forest in
      Terengganu, to study the species diversity, composition and stratification of
      fruit bats from the understorey to the forest canopy. Mist nets were set up at
      the understorey, sub-canopy and canopy layer while harp traps were set up at the
      understorey layer. We recorded 170 individuals from six families' compromised 21
      species from Hulu Terengganu dipterocarp forests and four species from Setiu
      Wetland BRIS forests throughout the sampling period. Megaerops ecaudatus and
      Cynopterus brachyotis were the most dominant species in Hulu Terengganu
      dipterocarp forest and Setiu Wetland BRIS forests. Our study also recorded two
      species with new distributional records for the east coast of Peninsular
      Malaysia, namely, Rhinolophus chiewkweeae and Chaerephon johorensis in Hulu
      Terengganu dipterocarp forests. Potential factors that might influence the
      results were in terms of the canopy covers, the structural complexity of canopy,
      food availability and spatial characteristics. This study was able to increase
      the knowledge on the species diversity and composition of bats in Hulu Terengganu
      dipterocarp forest and Setiu Wetland BRIS forest, thus, further aid in the effort
      of bat conservation in both areas.

PMID- 29644016
TI  - The Effect of Oxidative Stress Towards The Expression of Thiamine Biosynthesis
      Genes (THIC and THI1/THI4) in Oil Palm (Elaeis guineensis).
AB  - Thiamine is known to be an important compound in human diet and it is a cofactor
      required for vital metabolic processes such as acetyl-CoA biosynthesis, amino
      acid biosynthesis, Krebs and Calvin cycle. Besides that, thiamine has been shown
      to be involved in plant protection against stress. In this study, the level of
      expression of THIC and THI1/THI4, the genes for the first two enzymes in the
      thiamine biosynthesis pathway were observed when oil palm (Elaeis guineensis) was
      subjected to oxidative stress. Primers were designed based on the consensus
      sequence of thiamine biosynthesis genes obtained from Arabidopsis thaliana, Zea
      mays, Oryza sativa, and Alnus glutinosa. Oxidative stress were induced with
      various concentrations of paraquat and samplings were done at various time points
      post-stress induction. The expression of THIC and THI1/THI4 genes were observed
      via RT-PCR and qPCR analysis. The expression of THIC was increased 2-fold, while
      THI1/THI4 gene transcript was increased 4-fold upon induction of oxidative
      stress. These findings showed that oil palm responded to oxidative stress by over
      expressing the genes involved in thiamine biosynthesis. These findings support
      the suggestion that thiamine may play an important role in plant protection
      against stress.

PMID- 29644017
TI  - Morphological Characteristics and Habitats of Red Seaweed Gracilaria spp.
      (Gracilariaceae, Rhodophyta) in Santubong and Asajaya, Sarawak, Malaysia.
AB  - Red seaweed Gracilaria, one of the largest genus in Division Rhodophyta inhabits
      Sarawak coastal water. This study was designed to identify the species of
      Gracilaria using morphological approach and to assess selected water quality
      parameters in Gracilaria habitats. Three field samplings were carried out in
      Santubong and Asajaya, Sarawak from November 2013 to December 2014. Overall,
      three species were identified namely Gracilaria changii, G. blodgettii and G.
      coronopifolia, attached to net of cage culture in Santubong and root of mangrove
      trees in Asajaya. In addition, three different taxa of aquatic macroinvertebrates
      (polychaete, small crab, bivalve) and single species of red seaweed (Acanthophora
      sp.) were observed in Gracilaria assemblages. An estimate of 37% to 40% of the
      upper part of the cage net in Santubong was covered by seaweeds and only 16% to
      20% in Asajaya's mangrove. The study had provided better information on
      identification of Gracilaria and their habitat in Sarawak. Future work involving
      DNA barcoding of each species is in progress.

PMID- 29644018
TI  - Low pH Water Impairs the Tactile Sense of the Postlarvae of the Giant Freshwater
      Prawn Macrobrachium rosenbergii.
AB  - The effect of low pH on the tactile sense of Macrobrachium rosenbergii postlarvae
      was determined in the laboratory by means of two behavioural assays: shelter
      (netting) occupancy and jumping response to touch stimuli (taps) by a glass
      micropipette. The postlarvae were acclimated to pH 4, pH 5, pH 6 and pH 7.5
      (control) in 45 L aquaria 5-7 d before the experiments. Shelter occupancy
      decreased with pH and was significantly lower at pH 4 and pH 5 than at pH 6 and
      in the control. The jumping response instantly followed a tap 93-98% of the time
      in the control, pH 6 and pH 5 treatments. However, the postlarvae showed
      significantly lower jumping response (65%) at pH 4, indicating an impaired
      tactile sense. Low pH 4-5 probably degrades the chitin of the sensory setae and
      inhibits the surface mechanoreceptors of the prawn postlarvae.

PMID- 29644019
TI  - Effects of Incorporation of Jackfruit Rind Powder on Chemical and Functional
      Properties of Bread.
AB  - Nowadays, there is a rising interest towards consuming health beneficial food
      products. Bread-as one of the most popular food products-could be improved to
      'healthy bread' by addition of ingredients high in protein, dietary fiber and low
      in calorie. Incorporating Jackfruit rind powder (JRP) as a by-product rich in
      dietary fiber in bread, could not only provide health beneficial bread products,
      but also lead to develop an environmental friendly technology by solving the
      problem of waste disposal of residues. In this study, addition of jackfruit rind
      powder (JRP) as a high dietary fiber and functional ingredient in bread was
      examined. The results showed that incorporation of JRP in bread improved
      functional properties of flour such as Oil Holding Capacity (OHC), Water Holding
      Capacity (WHC) and pasting properties. Addition of 5%, 10% and 15% of JRP in
      wheat flour caused significantly (p < 0.05) higher insoluble, soluble and total
      dietary fiber in flour and bread products. Results from proximate composition
      indicated that all breads substituted with JRP, contained significantly (p <
      0.05) higher fiber, moisture and fat. Obtained results confirmed that the JRP has
      great potential in development of functional foods especially functional bread
      products.

PMID- 29644020
TI  - The Effects of Microalgae as Live Food for Brachionus plicatilis (Rotifer) in
      Intensive Culture System.
AB  - Brachionus plicatilis is used to feed fish and crustacean larvae in the
      aquaculture industry. It is well established that the type of microalgae may
      influence rotifer production. This experiment was conducted to determine the
      effect of five different locally available microalgae species at Fisheries
      Research Institute (FRI), Kampung Pulau Sayak, Kedah, Malaysia on the
      instantaneous growth rate (MU) of rotifer. Nannochloris sp., Tetraselmis sp.,
      Isochrysis sp., Chlorella sp., and Nannochloropsis sp. were used as feed at
      different algae densities (0.1, 0.3, 0.7 and 1.5 * 106 cells/ml) and culture
      volumes (20, 70 and 210 ml). At algae densities ranging from 0.3 to 1.5 * 106
      cells/ml, an average MU value of more than 0.90 per day were recorded for all
      algae species. However, at density of 0.1 * 106 cells/ml, only Tetraselmis sp.
      resulted in the significantly highest MU value compared with others (p < 0.05).
      In terms of volume, smaller culture volume of Tetraselmis sp. (20 ml) showed
      significantly higher MU compared with higher volume (70 and 210 ml cultures).

PMID- 29644021
TI  - The Distribution and Population Density of Bornean Tarsier, "Tarsius Bancanus
      Borneanus (Elliot)" in Secondary and Rehabilitated Forests of Universiti Putra
      Malaysia, Bintulu Sarawak Campus, Sarawak, Malaysia.
AB  - Tarsius bancanus borneanus was first reported by Elliot in 1990 which an endemic
      species that can be found on the Island of Borneo consisting of Sabah and Sarawak
      of Malaysia, Brunei Darussalam and Kalimantan, Indonesia. This sub-species has
      been listed as a totally protected animal under the Sarawak Wild Life Protection
      Ordinance (1998) and vulnerable by the International Union for Conservation of
      Nature (IUCN). The present study was conducted at Universiti Putra Malaysia
      Bintulu Campus (UPMKB), Sarawak from October 2014 till March 2015. Through mark
      and recapture sampling covering an area of 37 ha of secondary forest patches and
      7.13 ha of rehabilitated forest, a total of 16 tarsiers were captured using mist
      nets while one tarsier was recapture. The population density was 38
      individuals/km2 was captured using mist nets in the secondary forest while 28
      individuals/km2 was recorded for the rehabilitated forest. Using the catch per
      unit effort (net hour) method, the average time for capturing tarsiers in the
      secondary forest patches was 26.6 net hour per animal and 30.0 net hour per
      animal in the rehabilitated forest. The presented results provides information on
      the presence of tarsiers in both the secondary and rehabilitated forests of
      UPMKB, Sarawak, Malaysia which underlines the conservation value of these
      forested areas.

PMID- 29644022
TI  - Assessing Nesting Status of Green Turtles, Chelonia Mydas in Perak, Malaysia.
AB  - The nesting of green turtle (Chelonia mydas) was monitored from 1998 untill 2013
      along the beaches of Pasir Panjang, Segari, Perak. The objective of the study is
      to assess the nesting status of green turtles in Perak, Peninsular Malaysia in
      terms of total nests, eggs, survival hatchings, and density of visitors. A total
      number of green turtle nests found for 16 years were 1,019 nests and varied from
      10 to 220 nests per year. Meanwhile, the sum of eggs collected for 16 years were
      107,820 eggs, and varied from 553 to 20,881 eggs per year. The temporal pattern
      of nesting indicates year-round nesting in Perak in most years within the 16
      years period. The peak season of nesting was estimated to occur between May and
      June. Survival hatchlings varied from 23.33% (2,071 hatchlings) to 55.03% (5,018
      hatchlings) from 1998 to 2013. The density of visitors was not uniformly
      distributed among the years, and shows a sign of decline especially from 2006
      onwards. This publication provides basic knowledge of green turtle nesting
      population in Perak, and would be helpful in upgrading the conservation program
      in Malaysia. In future, we hope 1) for an increase in manpower to obtain accurate
      nesting records along the nesting beaches during nocturnal survey and, 2) to
      include the breeding biology data such as nest placement, emergence hour, and
      morphological characteristics of green turtle.

PMID- 29644023
TI  - Use of Pleurotus eous Strain P-31 Spent Mushroom Compost (SMC) as Soil
      Conditioner on the Growth and Yield Performance of Capsicum annuum L. and Solanum
      lycopersicon L. Seedlings under Greenhouse Conditions in Ghana.
AB  - The objective of this study was to investigate the influence of spent mushroom
      compost of Pleurotus eous strain P-31 on the growth and yield performance of
      pepper and tomato seedlings under greenhouse conditions. Sandy loam soil was
      combined with different percentages of SMC to obtain the following combinations
      (0, 5, 10, 15, 20, 25 and 30) %. Lower concentrations SMC5, SMC10 and SMC15
      promoted vegetative growth (plant height, leaf area, chlorophyll content, number
      of leaves and axillary branches) of the two test plants. Tomato seedlings grown
      in SMC10 recorded the highest plant height (50.3 +/- 7.2cm); leaf area (378.8 +/-
      1.2cm2); number of floral buds (51) and flowers (28) whereas SMC5 recorded the
      highest chlorophyll content 34.1 +/- 0.9CCI though SMC15 recorded the highest
      number of leaves (8). Tomato seedlings grown in SMC30 produced both the maximum
      number of fruits (8) with corresponding high weight (34.2 +/- 7.7g). Pepper
      seedlings grown in lower concentrations (SMC5-15) recorded the highest plant
      heights (29.8-30.8cm), chlorophyll content (20.3CCI) and leaf area (53.5-66.2
      cm2). Although the different combinations of sandy loam soil and SMC did not
      significantly (p >= 0.05) affect the number of axillary branches developed;
      different combinations significantly (p <= 0.05) affected the number of floral
      bud, flower and fruit, weight of fruits formed and value of each of these
      increased with increasing percentage of SMC. Pepper seedlings grown on SMC30
      recorded the maximum number of floral buds (32.0 +/- 3.6), number of flowers
      (19.4 +/- 1.3), number of fruits (10.8 +/- 1.2) and weight of fruits (31.9 +/-
      3.4g). Tomato seedlings raised on SMC100 (spent mushroom compost only) and soil
      only did not significantly (p >= 0.05) differ from each other however, was
      statistically significant (p <= 0.05) from amended sandy loam soil by all
      criteria investigated. The study shows that SMC provide favourable soil
      conditioners for the cultivation of fruits, vegetables and foliage crops as it
      improved growth and yield of tomato and pepper seedlings.

PMID- 29644024
TI  - A Comparative Study on Physicochemical Characteristics of Raw Goat Milk Collected
      from Different Farms in Malaysia.
AB  - This study was conducted to determine the physical and chemical composition of
      goat milk produced by eight local farms located in the central region of
      Malaysia. Farms 1 to 4 (F1-SC, F2-SP, F3-SP, F4-SBC) reared Saanen-type goats
      while farms 5 to 8 (F5-JK, F6-JPEC, F7-JTC, F8-JC), Jamnapari-type goats. The
      common feedstuffs used in all farms comprised of fresh or silage from Napier
      grass, feed pellets, and brans while two farms, F5-JK and F6-JPEC supplemented
      the feeds with soybean-based product. The total solid content, dry matter, and
      proximate composition of goat milk and feedstuffs from the different farms were
      determined and the results analysed using principal component analysis. Total
      solid content of goat milk from the Jamnapari crossbreed had the highest solid
      content ranging from 11.81% to 17.54% compared to milk from farms with Saanen and
      Saanen crossbreed (10.95% to 14.63%). Jamnapari-type goats from F5-JK, F6-JPEC,
      and F8-JC had significantly higher (p < 0.05) milk fat and protein contents
      (7.36%, 7.14%, and 6.59% fat; 5.08%, 6.19%, and 4.23% protein, respectively) than
      milk from other farms but, milk produced by Saanen-type goats from F4-SBC
      contained similar protein content (4.34%) to that from F8-JC. Total ash and
      carbohydrate contents in milk ranged between 0.67% to 0.86% and 3.26% to 4.71%,
      respectively, regardless of goat breed. Feeding soybean-based products appear to
      have a positive influence on milk fat and protein content in Jamnaparitype goats.

PMID- 29644025
TI  - Co-breeding Association of Aedes albopictus (Skuse) and Aedes aegypti (Linnaeus)
      (Diptera: Culicidae) in Relation to Location and Container Size.
AB  - The occurrence of major outbreaks of dengue, and other vector borne diseases such
      as chikungunya and zika in tropical and subtropical regions has rendered control
      of the diseases a top-priority for many affected countries including Malaysia.
      Control of the mosquito vectors Aedes aegypti and Aedes albopictus through the
      reduction of breeding sites and the application of insecticides to kill immature
      forms and adults are the main control efforts to combat these diseases. The
      present study describes the association between Ae. albopictus and Ae. aegypti in
      shared breeding sites. This study is important given that any measure taken
      against one species may affect the other. A yearlong larval survey was conducted
      in four dengue endemic areas of Penang Island. Sorenson's coefficient index
      indicated that no association between number of the immatures of the two species
      regardless of container size and study location. Therefore, the mean number Ae.
      albopictus immature was not decreased in the presence of Ae. aegypti in shared
      breeding container. However Ae. aegypti appeared to prefer breeding in habitats
      not occupied by Ae. albopictus, the two species sharing breeding sites only where
      available containers were limited. In control efforts, eliminating the preferred
      breeding containers for one species might not affect or reduce the population of
      the other species.

PMID- 29644026
TI  - Synergistic Apoptotic Effects of Tocotrienol Isomers and Acalypha wilkesiana on
      A549 and U87MG Cancer Cells.
AB  - Recent studies suggested that combined treatment approaches can be used to
      improve anticancer potency and circumvent the limitations of high-dose
      tocotrienols administration. Acalypha wilkesiana is a medicinal plant that has
      been used as an adjunct treatment for cancers in traditional medicine. Herein,
      the effects of single and combined treatments of beta-, gamma- and delta
      tocotrienols and ethyl acetate extract (9EA) of Acalypha wilkesiana on lung
      (A549) and brain (U87MG) cancer cells were investigated. gamma- and delta
      tocotrienols exhibited higher potent antiproliferative effects against A549 (12.1
      MUg/ml and 13.6 MUg/ml) and U87MG cells (3.3 MUg/ml and 5.2 MUg/ml) compared to
      beta-tocotrienols (9.4 MUg/ml and 92.4 MUg/ml), respectively. Whereas, 9EA
      induced potent antiproliferative effects against U87MG cells only (2.0 MUg/ml).
      Combined treatments of tocotrienols and 9EA induced a synergistic growth
      inhibition with up to 8.4-fold reduction in potent doses of beta-, gamma- and
      delta-tocotrienols on A549 cells. Apoptotic features were also evidenced on A549
      cells receiving single and combined treatments. The synergism may greatly improve
      the therapeutic outcome for lung cancer.

PMID- 29644027
TI  - Facilitation influences patterns of perennial species abundance and richness in a
      subtropical dune system.
AB  - Positive interactions in plant communities are under-reported in subtropical
      systems most likely because they are not identified as stressful environments.
      However, environmental factors or disturbance can limit plant growth in any
      system and lead to stressful conditions. For instance, salinity and low nutrient
      and water availability generate a gradient of stressful conditions in coastal
      systems depending on distance to shore. In a tropical coastal system in SE
      Brazil, we aimed to assess whether Guapira opposita, a shrub common in restinga
      environments, acted as nurse involved in ecological succession and which factors
      influenced its facilitation process. We sampled perennial species above 10 cm in
      height under the canopy of 35 G. opposita individuals and in neighbouring open
      areas. Shrub height, canopy area and distance to freshwater bodies were measured
      in the field, and distance to the ocean was obtained from aerial images. In
      addition, we measured the distance to the closest forest patch as a potential
      source of seeds. Plant abundance and species richness were higher under the
      canopy of G. opposita than in open areas. Facilitation by G. opposita was mainly
      determined by shrub height, which had a positive relationship with woody and
      bromeliads abundance and species richness while there was no relationship with
      the other factors. Overall, our data evidence that tropical environments may be
      highly stressful for plants and that nurse species play a key role in the
      regeneration of restinga environments, where their presence is critical to
      maintain ecosystem diversity and function.

PMID- 29644028
TI  - Relative contribution of reproductive attributes to the density-dependent effects
      on fruit-set.
AB  - Reproductive success of a plant species can be affected by the distribution
      pattern of its conspecifics in a small population. Besides the low mate
      availability, the dynamics of breeding system and pollination mechanism may also
      contribute to low fruit-set in such populations. We examined the relative
      contribution of these reproductive attributes on fruit-set across the contrasting
      distribution pattern (denser vs. sparser plots) in two isolated natural
      populations of a near-threatened tree species, Anogeissus sericea var.
      nummularia. Although flowers in the species are of generalist type, the narrow
      stigmatic surface appears to impose a requirement for a specialist pollinator.
      Pollination in the tree species is mediated only by the flies. The trees exhibit
      partial selfing and suffer from strong inbreeding depression at the early life
      history stages of the selfed progeny. We recorded significant difference between
      the denser and sparser plots in terms of inflorescence visits per tree, and the
      number of trees covered in a bout by the pollinators. Moreover, tree density
      showed a strong positive correlation with fruit-set. Besides the requirement of
      having proximity among the conspecifics to facilitate pollinator movement, pollen
      quality also seemed to be a crucial attribute in the reproductive success of the
      tree species. It is inferred that the mating pattern and fecundity of plants in
      small and isolated populations are significantly influenced by the extent of
      sexual incompatibility and magnitude of their dependence on pollinators.

PMID- 29644030
TI  - Proof of concept: liver splitting during normothermic machine perfusion.
AB  - Introduction: Despite utilizing extended criteria donors, there remains a
      shortage of livers for transplantation. No data exists on splitting donor livers
      with concurrent NMP-L. Methods: A liver recovered from a donor after circulatory
      death was subjected to NMP-L using a red cell based fluid. During NMP-L, a
      'classical' left lateral + right trisegmentectomy split was performed using an
      integrated bipolar/ultrasonic device. After splitting, blood flow was confirmed
      using Doppler ultrasound in each lobe. Results: Prior to splitting, flow rates
      were maintained physiologically. Lactate decreased from 13.9 to 3.0 mmol/L.
      Lactate before and after splitting were similar in the hepatic arteries, portal
      veins and IVC. Doppler ultrasound demonstrated arterial and venous waveforms in
      both lobes after splitting. Conclusions: 'Classical' liver splitting during NMP-L
      is feasible, maintaining viability of both lobes. Establishing this procedure may
      attenuate cold ischaemic injury, allow pre-implantation monitoring of both grafts
      and facilitate logistics of transplanting two grafts.

PMID- 29644032
TI  - Severe acute gallstone pancreatitis with diffuse hemorrhagic gastritis.
AB  - A 67-year-old male presented with acute pancreatitis secondary to gallstones,
      also known as acute biliary pancreatitis, and subsequently developed gastric
      outlet obstruction and was transferred to our hospital. A gastro-jejunal feeding
      tube was placed and an open cholecystectomy was performed. The patient had a
      pancreatic drain placed for interval increase in pancreatic necrosis and then
      nearly exsanguinated from gastroduodenal artery pseudoaneurysm bleed. This was
      managed by coiling the gastroduodenal artery. The patient underwent a pancreatic
      necrosectomy with malencot drain placement and developed a post-operative upper
      gastrointestinal bleeding. An EGD showed diffuse gastritis, but no varices. And
      18 days later the patient rebled, with the same diffuse gastritis. After further
      complications the patient elected to receive palliative care at a hospice
      facility. We are presenting this unusual case of diffuse, hemorrhagic gastritis
      after acute necrotizing pancreatitis.

PMID- 29644031
TI  - The use of magnetically controlled growing rods in paediatric Osteogenesis
      Imperfecta with early onset, progressive scoliosis.
AB  - Osteogenesis Imperfecta (OI) is a condition of bone fragility and can present
      with early onset scoliosis that can cause respiratory complications in later
      life. The fear of instrumenting the spine in OI is the possibility of fracture
      either on primary insertion or subsequent lengthening. Magnetically controlled
      growing rods were inserted to control a scoliosis in a 6-year old with OI type
      IV. Fixation was obtained using pedicle screws proximally and distally with
      sublaminar bands around the ribs proximally. These rods have been remotely
      lengthened on multiple occasions over a 2-year period. This has controlled the
      scoliosis whilst also allowing the spine to grow. There are no complications to
      report. This case reports the use of magnetically controlled growth rods used to
      manage early onset scoliosis in OI. Frequent lengthening, achieving small
      increases in length on every occasion protects against the risk of fracture
      during the lengthening procedure.

PMID- 29644029
TI  - Molecular, phylogenetic and developmental analyses of Sall proteins in
      bilaterians.
AB  - Background: Sall (Spalt-like) proteins are zinc-finger transcription factors
      involved in a number of biological processes. They have only been studied in a
      few model organisms, such as Drosophila melanogaster, Caenorhabditis elegans,
      Schmidtea mediterranea and some vertebrates. Further taxon sampling is critical
      to understand the evolution and diversification of this protein and its
      functional roles in animals. Results: Using genome and transcriptome mining, we
      confirmed the presence of sall genes in a range of additional animal taxa, for
      which their presence had not yet been described. We show that sall genes are
      broadly conserved across the Bilateria, and likely appeared in the bilaterian
      stem lineage. Our analysis of the protein domains shows that the characteristic
      arrangement of the multiple zinc-finger domains is conserved in bilaterians and
      may represent the ancient arrangement of this family of transcription factors. We
      also show the existence of a previously unknown zinc-finger domain. In situ
      hybridization was used to describe the gene expression patterns in embryonic and
      larval stages in two species of snails: Crepidula fornicata and Lottia gigantea.
      In L. gigantea, sall presents maternal expression, although later on the
      expression is restricted to the A and B quadrants during gastrulation and larval
      stage. In C. fornicata, sall has no maternal expression and it is expressed
      mainly in the A, C and D quadrants during blastula stages and in an asymmetric
      fashion during the larval stage. Discussion: Our results suggest that the
      bilaterian common ancestor had a Sall protein with at least six zinc-finger
      domains. The evolution of Sall proteins in bilaterians might have occurred mostly
      as a result of the loss of protein domains and gene duplications leading to
      diversification. The new evidence complements previous studies in highlighting an
      important role of Sall proteins in bilaterian development. Our results show
      maternal expression of sall in the snail L. gigantea, but not C. fornicata. The
      asymmetric expression shown in the ectoderm of the trochophore larva of snails is
      probably related to shell/mantle development. The observed sall expression in
      cephalic tissue in snails and some other bilaterians suggests a possible
      ancestral role of sall in neural development in bilaterians.

PMID- 29644033
TI  - A case of Dupuytren's disease managed with viable cryopreserved placental
      membrane adjunct to open palmar fasciectomy.
AB  - Dupuytren's disease (DD) is a rare connective tissue disorder resulting in
      progressive fibrosis and thickening of the palmar fascia, and contracture of the
      fingers due to excessive collagen deposition. Staged surgical interventions are
      reserved for severe cases, yet worsening of fibrosis and contracture of fingers
      post-surgery, has been reported to have a recurrence rate as high as 85%. Here,
      the authors report on use of viable cryopreserved placental membrane (vCPM)
      allograft as an adjunct to open fasciectomy. In a patient with debilitating
      bilateral DD contractures of >20 years duration, this novel approach resulted in
      a 34.8% range of motion (ROM) improvement and ability to fully extend all digits
      of the right hand. No adverse events were recorded. At 1 year post-surgery, the
      patient has no decrease in ROM. Results indicate that vCPM incorporation in open
      fasciectomy may provide benefit in reducing contracture recurrence in DD
      patients.

PMID- 29644034
TI  - Food ileus secondary to citrus fruit associated with a Meckel's diverticulum: a
      case report and review of the literature.
AB  - The case of an 11-year-old boy with an orange-associated ileus in the setting of
      a mesodiverticular band from a Meckel's diverticulum is reported herein. Computed
      tomography showed a small bowel feces sign. He underwent laparoscopic-assisted
      surgery, and intraoperative findings revealed a Meckel's diverticulum associated
      with a mesodiverticular band distal to dilated small bowel. After resection of
      the Meckel's diverticulum and inspection of the intestinal contents proximal to
      the obstruction, it was apparent that undigested food material was impacted
      proximal to the obstruction. Upon questioning postoperatively, it was revealed
      that the patient ate two citrus fruits with locular membranes several days prior
      to his clinical presentation. It was speculated that the combination of the
      citrus fruit impaction with the Meckel's band led to his obstruction. He was
      discharged uneventfully on postoperative Day 13. It is important to avoid eating
      large quantities of fruit rich in fiber and also to masticate well.

PMID- 29644035
TI  - Appendiceal intussusception in the setting of ulcerative colitis.
AB  - Appendiceal intussusception is a very rare condition with an estimated incidence
      of 0.01%. Most cases present in adults with chronic waxing and waning of symptoms
      over a period of weeks to months. We report a case of a 39-year-old Caucasian
      female with a 5-week history of worsening right-sided abdominal pain. Computed
      tomography revealed cecal thickening without visualization of the appendix. A
      colonoscopy revealed mild diffuse erythema and edema in the ascending colon as
      well as a mass within the lumen of the cecum. Biopsies of the colon were
      suggestive of mild ulcerative colitis (UC). The patient's symptoms continued and
      laparoscopic assisted ileocecectomy was performed revealing an inverted appendix
      protruding into the cecal lumen. The patient was discharged without any
      complications and began mesalamine therapy for her UC.

PMID- 29644036
TI  - Pulmonary paraganglioma in a 10-year-old: a case report and review of the
      literature.
AB  - Paraganglioma is a rare extra-adrenal tumor of the paraganglia often found in
      association with sympathetic and parasympathetic nerves. The case presented is of
      a 10-year-old boy with hemoptysis who was found to have an obstructive bronchial
      mass. He underwent surgical resection and biopsy confirmed primary pulmonary
      paraganglioma. He was subsequently found to have an associated genetic syndrome.
      This is the first case report describing a primary pulmonary paraganglioma in a
      child.

PMID- 29644037
TI  - Obstructive hydrocephalus secondary to odontoid pannus: case report and review of
      literature.
AB  - Odontoid pannus or periodontoid pseudotumour is associated with a variety of
      rheumatological conditions. We report a case of an 80-year old man who presented
      with acute hydrocephalus following an emergency operation to amputate his
      infected left big toe. Imaging revealed a large tissue mass causing severe
      compression at the cervico-medullary junction and obstruction of CSF flow. The
      acute hydrocephalus was presumed to be related to neck manoeuvring during general
      anaesthesia. Following an initial emergency CSF diversion through external
      ventricular drainage catheter insertion, the patient subsequently underwent
      ventriculo-peritoneal insertion and posterior spinal decompression and fixation.
      To our knowledge, there have been no reported cases of tophaceous gout of the
      odontoid pannus causing acute hydrocephalus.

PMID- 29644038
TI  - Calcific tendonitis of the quadriceps tendon.
AB  - A 61-year-old woman presented with chronic anterior pain and stiffness in the
      distal left thigh. Examination revealed swelling and tenderness immediately
      proximal to the patella. Radiographs showed opacities in the distal anterior
      thigh whilst MRI identified enlargement of the distal quadriceps tendon with
      splayed fibres separated by solid conglomerates. Dystrophic calcification of the
      quadriceps tendon was diagnosed. Blood tests revealed no systemic abnormalities
      in calcium handling. Arthroscopy of the left knee identified calcific deposits in
      the supra-patella pouch with surrounding synovitis. An open debridement of the
      tendon was performed; biopsy of the excised tendon showed chronic tenosynovitis
      with dystrophic calcification without evidence of malignancy. Post-operatively
      her knee was braced in extension enabling progressive flexion over 4 weeks.
      Anterior knee pain diminished post-operatively and 10 months following surgery
      the patient was pain free, able to walk normally and scored 99/100 on the
      Fulkerson modification of the Lysholm score.

PMID- 29644039
TI  - Giant anorectal condyloma acuminatum of Buschke-Lowenstein presents difficult
      management decisions.
AB  - Condyloma acuminata, or anogenital warts, caused by human papillomavirus are the
      most common sexually transmitted disease. In rare cases, the disease could
      progress to an extensive neoplasm called Buschke-Lowenstein tumor (BLT), also
      known as giant condyloma acuminatum. BLT differs from normal condyloma acuminata
      by presenting with locally invasive growth, lack of spontaneous resolution,
      tendency for recurrence after treatment and potential for malignant
      transformation. We examine a BLT case reaching large dimensions in the anorectal
      region treated with neoadjuvant chemoradiation therapy and surgical excision of
      residual lesions. Furthermore, continuous follow-up care can help identify and
      prevent recurrence or malignant transformation of the tumor.

PMID- 29644040
TI  - A rare case of a lingual mass in a neonate.
AB  - A large lingual cyst was noted on the 22-week antenatal ultrasound, which grew in
      proportion to the foetus on serial imaging. An elective c-section was performed
      in view of possible airway obstruction, and the neonate initially required oxygen
      to maintain saturations. Aged 1 month, the baby developed significant
      breastfeeding difficulties secondary to rapid cyst and secondary tongue
      enlargement, completely filling the oral cavity. Fifteen millilitres of fluid
      were aspirated in clinic, resulting in reduction of tongue size and immediate
      improvement in feeding. The patient subsequently underwent surgical excision of
      the cyst, which filled most of the anterior two-thirds of the tongue up to the
      foramen caecum. Histology supported the diagnosis of lingual thyroglossal duct
      cyst. A rare variant of thyroglossal duct cysts, these cysts can be potentially
      difficult to manage. More commonly located in the tongue base, we present an even
      rarer variant, that of an anterior tongue cyst.

PMID- 29644041
TI  - Paraganglioma or pheochromocytoma? A peculiar diagnosis.
AB  - Paragangliomas and pheochromocytomas are rare catecholamine secreting neoplasms
      that arise in the extra-adrenal autonomic paraganglia and adrenal medulla,
      respectively. Although typically presenting with paroxysms of headaches,
      palpitations, diaphoresis and hypertension, a broad spectrum of clinical
      manifestations may occur. Diagnosis relies on biochemical studies followed by
      adequate imaging investigation. Cross sectional morphological and functional
      imaging modalities have improved diagnostic accuracy and are crucial in the
      surgical planning. The authors report on a case of a 64-year-old female that
      presented with severe hypertension, palpitations and fatigue as the
      manifestations of a catecholamine secreting neoplasm. Abdominal contrast enhanced
      computer tomography revealed a right sided 78 mm adrenal medullary tumor
      suggestive of a pheochromocytoma. Standard therapeutical strategies were
      initially unsuccessful, and additional investigation and therapy were required to
      cure the patient. The challenges faced by the multidisciplinary team in the pre
      operative evaluation, medical management and surgical treatment are reported.

PMID- 29644042
TI  - Laparoscopic approach to non-communicating intestinal duplication cyst in adult.
AB  - Intestinal duplication is rare congenital pathology generally diagnosed in
      infancy or early childhood. Presentation in adults is extremely rare. We present
      a case of a 36-year-old otherwise healthy female patient without any past medical
      history. She presented with a month of lower abdominal pain, clinical examination
      revealed pain and a palpable mass in the lower abdomen. CT scan confirmed a
      cystic mass dependent of the cecum wall and colonoscopy showed an extrinsic
      compression of the lateral wall of the ascending colon. However, the mucosa and
      the rest of the colon appeared normal. Since pain became more intense laparoscopy
      was performed and a cystic mass dependent on the cecum was discovered.
      Laparoscopic hemicolectomy was performed. Patient underwent full recovery. On
      follow up controls, pathology described intestinal cystic duplication of the
      colonic wall.

PMID- 29644043
TI  - Inguinal hernia causing extrinsic compression of bilateral ureters leading to
      chronic obstructive uropathy.
AB  - Ureteral inguinal hernias are a well-documented cause of obstructive uropathy
      with ureteric involvement in the hernia sac. In this unique case, the left-sided
      inguinal hernia causes extrinsic compression of bilateral ureters outside of the
      hernia sac leading to chronic obstructive uropathy, which is demonstrated on non
      contrast CT and cystogram. This patient was managed with nephrostomy and
      subsequently antegrade stenting with nephrostomy removal. Prior to nephrostomy
      removal, nephrostogram demonstrated tapering of the left ureter in the pelvis.
      The patient's renal function continues to improve and is awaiting repair if his
      inguinal hernia after which he will have his ureteric stent removed.

PMID- 29644044
TI  - Abdominal wall extra-adrenal myelolipoma, a case report and review of the
      literature.
AB  - Extra-adrenal myelolipomas (EAMLs) are extremely rare soft tissue tumours that
      constitute <15% of all myelolipomas. We present a 70-year-old patient with a
      midline swelling of the anterior abdominal wall. It was clinically diagnosed as
      an incisional hernia, though the computerized scan indicated an internal hernia.
      During laparoscopy a soft tissue tumour of the abdominal wall was identified and
      excised. Pathology confirmed an extra-adrenal myelolipoma of the anterior
      abdominal wall through the presence of adipocytes and trilineage haematopoetic
      cell lines. EAMLs are rare mesenchymal soft tissue tumours with less than a
      hundred cases reported in the English literature. Pathological diagnosis shows
      the presence of mature adipocytes as well as myeloid and erythroid cell lines.
      This is the first case report of an EAML of the anterior abdominal wall. This
      case report is made even more rare as it is present in a male patient.

PMID- 29644045
TI  - Massive chronic irreducible rectal prolapse successfully treated with Altemeier's
      procedure.
AB  - The guideline for the treatment of rectal prolapse recommends that surgeons
      select appropriate surgical procedures individually based on each patient's
      overall status. However, in cases of irreducible or incarcerated rectal prolapse,
      surgical options are quite limited. Here we present a case of an elderly woman
      with massive chronic irreducible rectal prolapse. An 87-year-old woman presented
      to our hospital with a complaint of massive rectal prolapse. The prolapsed rectum
      was over 20 cm long, and completely irreducible. She underwent perineal
      rectosigmoidectomy with levatorplasty known as Altemeier's procedure. More than
      30 cm of rectosigmoid colon was resected. After the operation, rectal prolapse
      was resolved completely. Her postoperative course was uneventful, and her quality
      of life and bowel movements improved. She has since been healthy without
      recurrence for over 2 years. Altemeier's procedure is applicable even in cases of
      irreducible rectal prolapse and features acceptable safety and a satisfactory
      outcome.

PMID- 29644046
TI  - Mitral valve replacement for Libman-Sacks endocarditis in a patient with
      antiphospholipid syndrome secondary to systemic lupus erythematosus.
AB  - Libman-Sacks endocarditis is a relatively rare sterile verrucous vegetative
      lesion observed in systemic lupus erythematosus (SLE)/antiphospholipid syndrome
      (APLS) patients. Most patients with this condition are asymptomatic. Here we
      report a case of a 46-year-old woman with APLS secondary to SLE complicated with
      frequent thromboembolic events due to a mitral valve mass. We performed minimally
      invasive mitral valve replacement with a mechanical prosthetic valve, and she was
      successfully discharged 14 days after surgery. Thus, Libman-Sacks endocarditis
      may be an indication for mitral valve replacement.

PMID- 29644047
TI  - Two patients with spontaneous transomental hernia treated with laparoscopic
      surgery: a review.
AB  - Here, we report two patients with transomental hernia who were successfully
      treated with laparoscopic surgery. The first patient was a 58-year-old female who
      presented to our hospital with abdominal pain and vomiting; she had no history of
      abdominal surgery. Enhanced computed tomography revealed strangulation ileus due
      to an internal hernia. The second patient was a 36-year-old male who presented to
      our hospital with abdominal pain and no history of abdominal surgery. Enhanced
      computed tomography indicated transomental hernia. Emergency laparoscopic surgery
      in both patients revealed incarcerated bowel loops through defects in the greater
      omentum. The bowel segments were laparoscopically released, and the patients were
      uneventfully discharged on postoperative Days 4 and 8. Laparoscopic surgery is
      useful for the diagnosis and treatment of small bowel obstruction due to
      transomental hernia through the greater omentum.

PMID- 29636897
TI  - Monocytes isolated by positive and negative magnetic sorting techniques show
      different molecular characteristics and immunophenotypic behaviour.
AB  - Background: Magnetic sorting of cells, based on  microbead conjugated antibodies
      (Abs), employs positive as well as negative immunomagnetic separation methods,
      for isolation of a specific cell population. These microbeads are suggested to be
      nontoxic, biodegradable carriers conjugated to various antibodies. Isolation of
      cells through positive selection involves the attachment of antibody conjugated
      microbeads to the cells of interest, followed by their isolation in the presence
      of a strong magnetic field to obtain higher purity. Negative selection involves
      attachment of microbead conjugated antibodies to all other cell populations
      except the cells of interest, which remain untagged. In the present study, we
      compared the two methods for their effect on functional and immunophenotypic
      behavior of isolated CD14+ monocytes. Methods: Peripheral blood mononuclear cells
      (PBMCs) were isolated from blood collected from healthy volunteers by density
      gradient centrifugation. Human blood derived monocytes were isolated through
      positive selection and negative selection, making use of the appropriate monocyte
      isolation kit. Monocytes were then stimulated with lipopolysaccharide (LPS) and
      their activation and proliferation capacity were examined. The degradation or
      dissociation of cell-bound microbeads was also investigated. Results: We observed
      an impaired LPS sensitivity as well as poor activation and proliferation capacity
      upon stimulation by LPS in positively sorted CD14+ monocytes as compared to
      negatively sorted CD14+ monocytes. The attached microbeads did not degrade and
      remained attached to the cells even after 6 days of culture. Conclusions: Our
      results suggest that positively sorted CD14+ cells exhibit hampered functionality
      and may result in inaccurate analysis and observations in downstream
      applications. However, these cells can be used for immediate analytical
      procedures.

PMID- 29636901
TI  - Case Report: III degrees  atrioventricular block due to fulminant myocarditis
      managed with non-invasive transcutaneous pacing.
AB  - Fulminant myocarditis is a life-threatening clinical condition. It is the
      inflammation of myocardium leading to acute heart failure, cardiogenic shock and
      cardiac arrhythmias. Incidence of fulminant myocarditis is low and mortality is
      high. Most grievous complications of fulminant myocarditis is mainly cardiac
      arrhythmias; if there is delay on active management of the patient, it may be
      fatal. Here, we describe a case of III degrees  atrioventricular block due to
      fulminant myocarditis that was managed with non-invasive transcutaneous cardiac
      pacing in the absence of ECMO. The non-invasive transcutaneous pacemaker is a
      safe, effective and convenient device to revert arrhythmias.

PMID- 29644050
TI  - Correction to: American Society for Enhanced Recovery (ASER) and Perioperative
      Quality Initiative (POQI) Joint Consensus Statement on Optimal Analgesia within
      an Enhanced Recovery Pathway for Colorectal Surgery: Part 2-From PACU to the
      Transition Home.
AB  - [This corrects the article DOI: 10.1186/s13741-017-0063-6.].

PMID- 29644051
TI  - Correction to: American Society for Enhanced Recovery (ASER) and Perioperative
      Quality Initiative (POQI) joint consensus statement on perioperative fluid
      management within an enhanced recovery pathway for colorectal surgery.
AB  - [This corrects the article DOI: 10.1186/s13741-016-0049-9.].

PMID- 29644052
TI  - Environmental colonization and onward clonal transmission of carbapenem-resistant
      Acinetobacter baumannii (CRAB) in a medical intensive care unit: the case for
      environmental hygiene.
AB  - Background: In May 2015, we noticed an increase in carbapenem-resistant
      Acinetobacter baumannii (CRAB) infections in the Medical Intensive Care Unit
      (MICU). To investigate this, we studied the extent of environmental contamination
      and subsequent onward clonal transmission of CRAB. Methods: We conducted a one
      day point prevalence screening (PPS) of the patients and environment in the MICU.
      We screened patients using endotracheal tube aspirates and swabs from nares,
      axillae, groin, rectum, wounds, and exit sites of drains. We collected
      environmental samples from patients' rooms and environment outside the patients'
      rooms. CRAB isolates from the PPS and clinical samples over the subsequent one
      month were studied for genetic relatedness by whole genome sequencing (WGS).
      Results: We collected 34 samples from seven patients and 244 samples from the
      environment. On the day of PPS, we identified 8 CRAB carriers: 3 who screened
      positive and 5 previously known clinical infections. We detected environmental
      contamination in nearly two-thirds of the rooms housing patients with CRAB. WGS
      demonstrated genetic clustering of isolates within rooms but not across rooms. We
      analysed 4 CRAB isolates from clinical samples following the PPS. One genetically
      related CRAB was identified in the respiratory sample of a patient with
      nosocomial pneumonia, who was admitted to the MICU five days after the PPS.
      Conclusion: The extensive environmental colonization of CRAB by patients
      highlights the importance of environmental hygiene. The transmission dynamics of
      CRAB needs further investigation.

PMID- 29644053
TI  - The dialysis orders objective structured clinical examination (OSCE): a formative
      assessment for nephrology fellows.
AB  - Background: Few quantitative nephrology-specific simulations assess fellow
      competency. We describe the development and initial validation of a formative
      objective structured clinical examination (OSCE) assessing fellow competence in
      ordering acute dialysis. Methods: The three test scenarios were acute continuous
      renal replacement therapy, chronic dialysis initiation in moderate uremia and
      acute dialysis in end-stage renal disease-associated hyperkalemia. The test
      committee included five academic nephrologists and four clinically practicing
      nephrologists outside of academia. There were 49 test items (58 points). A
      passing score was 46/58 points. No item had median relevance less than
      'important'. The content validity index was 0.91. Ninety-five percent of positive
      point items were easy-medium difficulty. Preliminary validation was by 10 board
      certified volunteers, not test committee members, a median of 3.5 years from
      graduation. The mean score was 49 [95% confidence interval (CI) 46-51], kappa =
      0.68 (95% CI 0.59-0.77), Cronbach's alpha = 0.84. Results: We subsequently
      administered the test to 25 fellows. The mean score was 44 (95% CI 43-45); 36%
      passed the test. Fellows scored significantly less than validators (P < 0.001).
      Of evidence-based questions, 72% were answered correctly by validators and 54% by
      fellows (P = 0.018). Fellows and validators scored least well on the acute
      hyperkalemia question. In self-assessing proficiency, 71% of fellows surveyed
      agreed or strongly agreed that the OSCE was useful. Conclusions: The OSCE may be
      used to formatively assess fellow proficiency in three common areas of acute
      dialysis practice. Further validation studies are in progress.

PMID- 29644054
TI  - Exploring the uncharted territory of social media: the next frontier of medical
      education in nephrology.
AB  - Social media is gaining popularity amongst both medical educators and life-long
      learners. One of the most popular social media platforms used by the medical
      community is Twitter, which is popular amongst physicians, students and patients,
      and particularly in medical societies. Major international and regional societies
      commonly use Twitter to amplify their reach beyond what their live annual
      meetings can achieve. There has been a unique and notable effort by Nephrology
      societies to craft a structured social media strategy that results in the
      broadest reach to the community of nephrology providers. We report on the first
      three such experiments performed by three separate nephrology organizations.

PMID- 29644055
TI  - Pretreatment of enteral nutrition with sodium polystyrene sulfonate: effective,
      but beware the high prevalence of electrolyte derangements in clinical practice.
AB  - Background: Current treatment options for chronic hyperkalemia in children with
      chronic kidney disease include dietary restrictions or enteral sodium polystyrene
      sulfonate (SPS); however, dietary restrictions may compromise adequate nutrition
      and enteral SPS may be limited by palatability, adverse effects and feeding tube
      obstruction. A potentially safer alternative is to pretreat enteral nutrition
      (EN) with SPS prior to consumption. The purpose of this study was to evaluate the
      efficacy and safety of pretreating EN with SPS in pediatric patients with
      hyperkalemia. Methods: We performed a retrospective cohort study between
      September 2012 and May 2016 at the Children's Hospital of Philadelphia. In all,
      14 patients (age range 0.5-53.2 months) who received 19 courses of SPS
      pretreatment of EN were evaluated. Serum electrolytes were evaluated at baseline
      and within 1 week of initiating therapy. The primary endpoint was mean change in
      potassium at 7 days. Secondary endpoints included the mean change in serum
      sodium, chloride, bicarbonate, calcium, phosphorous and magnesium, as well as the
      percentage of patients who developed electrolyte abnormalities within the first
      week of treatment. Results: Serum potassium levels decreased from 6.0 to 4.4
      mmol/L (P < 0.001) and serum sodium levels increased from 135.8 to 141.3 mmol/L
      (P = 0.008) 1 week after initiating SPS pretreatment. No significant differences
      in mean serum calcium or magnesium levels were noted. Nevertheless, more than
      half of the courses resulted in at least one electrolyte abnormality, with
      hypokalemia (31.6%), hypernatremia (26.3%) and hypocalcemia (21.1%) occurring
      most frequently. Conclusions: Pretreatment of EN with SPS is an effective method
      for treating chronic hyperkalemia in pediatric patients; however, close
      monitoring of electrolytes is warranted.

PMID- 29644056
TI  - Lung ultrasonography in end-stage renal disease: moving from evidence to practice
      a narrative review.
AB  - Traditionally, point of care ultrasonography in nephrology has been used for
      renal biopsies and dialysis line placement. However, there is an emerging
      literature supporting the value of point of care lung ultrasonography in the
      assessment of volume status for dialysis patients. We conducted a review and
      identified 12 studies that examined the utility of lung ultrasonography in
      assessing volume status in patients with end-stage renal disease. We conclude
      that lung ultrasonography can be used to determine volume status in chronic
      dialysis patients by identifying lung congestion using the B-line score.
      Incorporating this technique into practice may have significant diagnostic and
      prognostic value for this high-risk population, as it provides the nephrologist
      with a useful bedside technique to assess extravascular lung water. Developing
      competence in lung ultrasonography is straightforward. The nephrology community
      should consider adding this useful tool into fellowship training, paralleling its
      broader use in other internal medicine specialties.

PMID- 29644057
TI  - Clinical and pathological phenotype of genetic causes of focal segmental
      glomerulosclerosis in adults.
AB  - Focal segmental glomerulosclerosis (FSGS) is a histologic lesion resulting from a
      variety of pathogenic processes that cause injury to the podocytes. Recently,
      mutations in more than 50 genes expressed in podocyte or glomerular basement
      membrane were identified as causing genetic forms of FSGS, the majority of which
      are characterized by onset in childhood. The prevalence of adult-onset genetic
      FSGS is likely to be underestimated and its clinical and histological features
      have not been clearly described. A small number of studies of adult-onset genetic
      FSGS showed that there is heterogeneity in clinical and histological findings,
      with a presentation ranging from sub-nephrotic proteinuria to full nephrotic
      syndrome. A careful evaluation of adult-onset FSGS that do not have typical
      features of primary or secondary FSGS (familial cases, resistance to
      immunosuppression and absence of evident cause of secondary FSGS) should include
      a genetic evaluation. Indeed, recognizing genetic forms of adult-onset FSGS is of
      the utmost importance, given that this diagnosis will have major implications on
      treatment strategies, selecting of living-related kidney donor and renal
      transplantation success.

PMID- 29644058
TI  - Porphyria and kidney diseases.
AB  - The kidneys, after the bone marrow and liver, are third in terms of the amounts
      of haem synthesized daily. Haem is incorporated into haemoproteins that are
      critical to renal physiology. In turn, disturbances in haem metabolism interfere
      with renal physiology and are tightly interrelated with kidney diseases. Acute
      intermittent porphyria causes kidney injury, whereas medical situations
      associated with end-stage renal disease, such as porphyrin accumulation, iron
      overload and hepatitis C, participate in the inhibition of uroporphyrinogen
      decarboxylase and predispose the individual to porphyria cutanea tarda. Even if
      some of these interactions have been known for a long time, the clinical
      situations associated with these interrelations have strikingly evolved over time
      with the advent of new therapeutic strategies for dialysis therapy and a better
      understanding of the pathophysiological mechanisms of porphyria-associated kidney
      disease. Physicians should be aware of these interactions. The aim of this review
      is to summarize the complex interactions between kidney physiology and pathology
      in the settings of porphyria and to emphasize their often-underestimated
      importance.

PMID- 29644059
TI  - Mutations in membrane cofactor protein (CD46) gene in Indian children with
      hemolytic uremic syndrome.
AB  - Background: Mutations in the CD46 gene account for an important proportion of
      patients with atypical hemolytic uremic syndrome (aHUS) who characteristically
      show multiple relapses, no response to plasma exchange and low recurrence risk in
      allograft. We screened for mutations in CD46 in patients with and without
      circulating anti-factor H (FH) antibodies-associated aHUS. Methods: We estimated
      CD46 surface expression by flow cytometry and sequenced the CD46 gene in 23 and
      56 patients with and without circulating anti-FH antibodies, respectively. Human
      Splicing Finder and PolyPhen2 were used for in silico prediction of
      pathogenicity. Results: Two novel and three known (c.286 +2T > G, c.104G > A and
      c.565T > G) mutations in CD46 were found in nine (11.4%) patients; one patient
      had a variant of unknown significance and two patients presented during the first
      year of life. Novel intronic (c.1127 + 46C > G) and exonic (c.911C > T) mutations
      are proposed to activate cryptic splicing sites or alter protein conformation.
      Markedly reduced CD46 surface expression was found in homozygous states in five
      patients. Conclusion: Patients with mutations in CD46 present at all ages,
      including the first year of life. Mutations in intron 2, (c.286 +2T > G) may be a
      potential hot spot in Indian children. Flow cytometry for CD46 expression is a
      satisfactory screening tool enabling early diagnosis.

PMID- 29644060
TI  - Infected renal cyst presented with pleural effusion in a woman with autosomal
      dominant polycystic kidney disease.
AB  - We present a 64-year-old woman with autosomal dominant polycystic kidney disease
      and hepatic cysts admitted to our hospital for high fever, intense coughing and
      right abdominal pain. The chest X-ray showed right pleural effusion suggestive of
      pneumonia. An abdominal ultrasound and computed tomography (CT) were done but did
      not show evidence of cyst infection or other abdominal complications. A gallium
      67-citrate single-photon emission CT/CT, a relatively cheaper technique than
      positron emission tomography/CT was performed. This revealed an infected kidney
      cyst that was the cause of the right pleural effusion and fever.

PMID- 29644061
TI  - Interstitial inflammation and interstitial fibrosis and tubular atrophy predict
      renal survival in lupus nephritis.
AB  - Background: This study examines the effect of interstitial inflammation and
      interstitial fibrosis and tubular atrophy on renal survival in lupus nephritis.
      Methods: Baseline characteristics, initial (n = 301) and repeat biopsies (n = 94)
      and clinical outcomes for patients with biopsy-proven lupus nephritis from 1998
      to 2014 were retrospectively collected from the medical record. Clinical and
      morphologic variables were evaluated using a Cox proportional hazards model and
      multiple imputation to address missing data. Renal survival was defined as the
      time from initial biopsy to end-stage renal disease [estimated glomerular
      filtration rate (eGFR) <15 mL/min/1.73 m2], dialysis or transplant. Results: A
      total of 218 patients had follow-up and Class IV had worse renal survival,
      especially in patients with active and chronic glomerular lesions {relative to
      non-IV; Class IV-A: hazard ratio [HR] 0.92 [95% confidence interval (CI) 0.41
      2.04], Class IV-AC: HR 5.02 [95% CI 2.70-9.36]}. Interstitial inflammation grade
      [relative to interstitial inflammation <5%; interstitial inflammation 5-25%: HR
      2.36 (95% CI 1.13-4.91), interstitial inflammation 25-50%: HR 3.84 (95% CI 1.53
      9.62), interstitial inflammation >50%: HR 7.67 (95% CI 3.75-15.67)] and increased
      interstitial fibrosis and tubular atrophy (IFTA) category [relative to IFTA <5%;
      IFTA 5-25%: HR 3.93 (95% CI 1.58-9.75), IFTA 25-50%: HR 4.01 (95% CI 1.37-11.70),
      IFTA >50%: HR 13.99 (95% CI 4.91-39.83)] predicted worse renal survival among all
      patients and those with Class IV on initial and repeat biopsy (n = 94) in a dose
      dependent manner. Interstitial inflammation grade and IFTA category were
      significant predictors of renal survival in a multivariable model adjusted for
      age, gender, race, ethnicity and serum creatinine. Conclusions: Interstitial
      inflammation and IFTA independently affect renal survival and grading these
      lesions stratifies risk within the International Society of Nephrology and Renal
      Pathology Society classification of lupus nephritis.

PMID- 29644062
TI  - Granulomatous interstitial nephritis secondary to adalimumab therapy.
AB  - Tumour necrosis factor alpha (TNF-alpha) inhibitors are frequently used for the
      treatment of immune-mediated diseases. Conversely, cytokine therapy has the
      potential to paradoxically induce autoimmunity. A number of case reports have
      emerged concerning sarcoid-like granulomatosis secondary to TNF-alpha therapy, an
      adverse effect that typically affects the pulmonary and cutaneous systems.
      Granulomatous interstitial nephritis (GIN) is a relatively unknown, relatively
      under-reported consequence of adalimumab therapy that can have important clinical
      implications. To our knowledge, this is the first case report of GIN secondary to
      anti-TNF-alpha therapy necessitating a prolonged period of dialysis and the first
      report demonstrating the successful use of secukinumab as an alternative
      immunomodulatory agent.

PMID- 29644063
TI  - Metabolic adaptability in hexavalent chromium-treated renal tissue: an in vivo
      study.
AB  - Background: Hexavalent chromium [Cr(VI)], an environmental pollutant that
      originates mostly from anthropogenic sources, is a serious threat to human
      health. After entering into cells, Cr(VI) is capable of producing excessive free
      radicals and causing tissue damage. The present study aims to reveal the toxic
      manifestation of Cr(VI) on the metabolic activity of renal tissue. Methods: Male
      Swiss albino mice were treated orally with potassium dichromate (K2Cr2O7) at a
      dose of 10 mg/kg body weight for a period of 30 days. Important tricarboxylic
      acid (TCA) cycle enzyme activities like isocitrate dehydrogenase, succinate
      dehydrogenase and malate dehydrogenase, as well as the activities of enzymes
      involved in oxidative phosphorylation such as Nicotinamide adenine dinucleotide
      (NADH) dehydrogenase, were measured. Additionally, transaminase and protease
      (pronase, cathepsin and trypsin) activities, tissue protein and free amino
      nitrogen were estimated in renal tissue. Glucose-6-phosphatase, glucose-6
      phosphate dehydrogenase and alkaline phosphatase activities, as well as lactic
      acid, pyruvic acid and chromium contents, of kidneys were determined following
      standard protocols. Kidney histology was performed by hematoxylin and eosin
      staining. Results: Cr(VI) suppresses the rate-limiting enzymes of the TCA cycle
      and oxidative phosphorylation indicating an inhibition of renal ATP production.
      It decreases protease activity by eliminating the protein substrates and alters
      the gluconeogenic pathway. Cr(VI) worsens the normophysiological attributes of
      renal tissue by enhancing the activity of alkaline phosphatase, pointing towards
      kidney disease. Histopathological observations confirmed these biochemical
      results through the presence of chronic tubular nephritis and altered glomerular
      structure. Cr(VI) retention occurs to a greater extent in renal tissue, which
      intensifies the toxic manifestation of this pollutant in the kidney. Conclusions:
      Cr(VI) disrupts the metabolic interaction between carbohydrates and proteins in
      mammalian renal tissue.

PMID- 29644064
TI  - Intensive haemodialysis using PMMA dialyser does not increase renal response rate
      in multiple myeloma patients with acute kidney injury.
AB  - Background: Intensive haemodialysis (IHD) in addition to bortezomib-based
      chemotherapy might be efficient to rapidly decrease serum immunoglobulin-free
      light chains removal in patients with multiple myeloma (MM) and to improve renal
      prognosis and survival. Methods: The aim of this retrospective multi-centre study
      was to compare the efficacy (renal recovery rate) of IHD and of standard
      haemodialysis (SHD) in patients with MM and dialysis-dependent acute kidney
      injury (AKI), concomitantly treated with bortezomib-based chemotherapy. Results:
      We selected 41 patients with MM and dialysis-dependent AKI, most likely due to
      myeloma cast nephropathy (MCN), and who were treated in eight French hospitals
      between January 2007 and June 2011. Patients were classified in two groups
      according to dialysis regimen: IHD [n = 21, with a mean of 11.3 dialysis sessions
      all with poly(methyl methacrylate) (PMMA) membranes for 13.2 days] and SHD (n =
      20 patients, mostly three times per week, 31% with PMMA membrane). The main
      outcome was dialysis-independence at 3 months. At 3 months, 15 patients could
      stop dialysis: 8 (38.1%) in the IHD and 7 (35%) in the SHD group (P = 1).
      Moreover, 14 (56%) of the 25 patients who did show haematological response and
      only one of the 16 patients who did not were dialysis-independent (P = 0.002) at
      3 months. Conclusions: The results of this retrospective study did not show any
      clear renal benefit of IHD in patients with MM and MCN compared with SHD.
      Conversely, they underline the importance of the haematological response to
      chemotherapy for the renal response and patient prognosis.

PMID- 29644066
TI  - Patterns of progression of chronic kidney disease at later stages.
AB  - Background: At later stages of chronic kidney disease (CKD), a pattern of linear
      and irreversible renal function decline is thought to be the most common. The
      objective of this study was to describe the characteristics of the different
      patterns of CKD progression, and to investigate potentially modifiable factors
      associated with the rate of decline of renal function. Methods: This was a
      retrospective, observational study in a cohort of adult patients with CKD Stage 4
      or 5 not on dialysis. Decline in renal function was estimated as the slope of the
      individual linear regression line of estimated glomerular filtration rate (eGFR)
      over time. The following patterns of CKD progression were considered:
      unidentifiable, linear, nonlinear (curvilinear) and positive (improvement of
      renal function). Results: The study group consisted of 915 patients (mean +/-SD
      age 65 +/- 14 years, 48% females, median follow-up time 16 months). A linear
      pattern was observed in 38%, unidentifiable in 23%, nonlinear in 24% and positive
      in 15% of the study patients. The mean eGFR slope was: -3.35 +/- 4.45
      mL/min/year. Linear and unidentifiable patterns were associated with more rapid
      loss of renal function. By multiple linear and logistic regression analysis, the
      magnitude of proteinuria, the systolic blood pressure and the treatment with dual
      renin-angiotensin system blockade were associated with more rapid CKD
      progression. On the contrary, older age and discontinuation of commonly
      prescribed medication with potential influence on renal function or eGFR
      measurements were associated with slower CKD progression. Conclusions: A majority
      of patients with advanced CKD show patterns of renal function decline different
      from linear, and several of the main determinants of CKD progression are
      potentially modifiable.

PMID- 29644067
TI  - A scheme based on ICD-10 diagnoses and drug prescriptions to stage chronic kidney
      disease severity in healthcare administrative records.
AB  - Background: Information about renal function is important for drug safety studies
      using administrative health databases. However, serum creatinine values are
      seldom available in these registries. Our aim was to develop and test a simple
      scheme for stratification of renal function without access to laboratory test
      results. Methods: Our scheme uses registry data about diagnoses, contacts,
      dialysis and drug use. We validated the scheme in the Stockholm CREAtinine
      Measurements (SCREAM) project using information on approximately 1.1 million
      individuals residing in the Stockholm County who underwent calibrated creatinine
      testing during 2006-11, linked with data about health care contacts and filled
      drug prescriptions. Estimated glomerular filtration rate (eGFR) was calculated
      with the CKD-EPI formula and used as the gold standard for validation of the
      scheme. Results: When the scheme classified patients as having eGFR <30
      mL/min/1.73 m2, it was correct in 93.5% of cases. The specificity of the scheme
      was close to 100% in all age groups. The sensitivity was poor, ranging from 68.2%
      in the youngest age quartile, down to 10.7% in the oldest age quartile. Age
      related decline in renal function makes a large proportion of elderly patients
      fall into the chronic kidney disease (CKD) range without receiving CKD diagnoses,
      as this often is seen as part of normal ageing. Conclusions: In the absence of
      renal function tests, our scheme may be of value for identifying patients with
      moderate and severe CKD on the basis of diagnostic and prescription data for use
      in studies of large healthcare databases.

PMID- 29644065
TI  - Frailty and chronic kidney disease: current evidence and continuing
      uncertainties.
AB  - Frailty, the state of increased vulnerability to physical stressors as a result
      of progressive and sustained degeneration in multiple physiological systems, is
      common in those with chronic kidney disease (CKD). In fact, the prevalence of
      frailty in the older adult population is reported to be 11%, whereas the
      prevalence of frailty has been reported to be greater than 60% in dialysis
      dependent CKD patients. Frailty is independently linked with adverse clinical
      outcomes in all stages of CKD and has been repeatedly shown to be associated with
      an increased risk of mortality and hospitalization. In recent years there have
      been efforts to create an operationalized definition of frailty to aid its
      diagnosis and to categorize its severity. Two principal concepts are described,
      namely the Fried Phenotype Model of Physical Frailty and the Cumulative Deficit
      Model of Frailty. There is no agreement on which frailty assessment approach is
      superior, therefore, for the time being, emphasis should be placed on any efforts
      to identify frailty. Recognizing frailty should prompt a holistic assessment of
      the patient to address risk factors that may exacerbate its progression and to
      ensure that the patient has appropriate psychological and social support.
      Adequate nutritional intake is essential and individualized exercise programmes
      should be offered. The acknowledgement of frailty should prompt discussions that
      explore the future care wishes of these vulnerable patients. With further study,
      nephrologists may be able to use frailty assessments to inform discussions with
      patients about the initiation of renal replacement therapy.

PMID- 29644068
TI  - The relationship between kidney function and quality of life among community
      dwelling adults varies by age and filtration marker.
AB  - Background: The impact of a diminished level of kidney function on the well-being
      of an older individual is poorly understood. We sought to determine the
      association between estimated glomerular filtration rate (eGFR) and overall
      quality of life (QoL) among older adults. Methods: Cross-sectional analysis of
      4293 participants from the Irish Longitudinal Study on Ageing, a population-based
      study of community-dwelling adults >=50 years of age. We used multivariable
      negative binomial regression to model the relationship between categories of
      cystatin C eGFR (eGFRcys) or creatinine eGFR (eGFRcr) and the number of QoL
      deficits from the Control, Autonomy, Self-realization and Pleasure (CASP-19)
      scale, a holistic measure of QoL among older adults (range 0-57). We further
      explored this relationship across age strata. Results: Median age was 61
      [interquartile range (IQR) 55-68] years, 53% were female, mean (SD) CASP-19 score
      was 44.8 (7.4) and median eGFRcys was 81 (IQR 68-93) mL/min/1.73 m2. After
      multivariable adjustment, participants with eGFRcys <45 mL/min/1.73 m2 had 14%
      greater QoL deficits {incidence rate ratio 1.14 (95% confidence interval 1.03
      1.25)] relative to the reference group (eGFRcys >=90 mL/min/1.73 m2). This
      relationship appeared linear across eGFRcys categories and was more pronounced in
      younger (50-64 years) compared with older participants (65-74 or >=75 years).
      There was no substantive relationship between eGFRcr and CASP-19. Conclusions:
      Cystatin C but not creatinine eGFR was associated with clinically modest declines
      in QoL among a large sample of community-dwelling older adults. This relationship
      varied by age, suggesting that a diminished eGFR contributes little to overall
      QoL beyond middle age in this population.

PMID- 29644069
TI  - Clinical course after parathyroidectomy in adults with end-stage renal disease on
      maintenance dialysis.
AB  - Background: Parathyroidectomy (PTX) is done in cases of secondary
      hyperparathyroidism from chronic kidney disease to improve renal osteodystrophy.
      Despite this widespread practice, clinical outcomes regarding the benefits of
      this procedure are still lacking. Most studies in the literature have opted to
      report the laboratory outcome instead. Our study aimed to evaluate the
      postoperative clinical course for patients who had undergone total PTX without
      autoimplantation. Methods and results: All patients who underwent PTX between
      January 2010 and February 2014 in a tertiary referral center were included in
      this study and followed up for 12 months. Laboratory outcome parameters include
      various preoperative and postoperative serial measurements of laboratory
      parameters. Patients' hospitalizations and mortality records post-PTX were also
      retrieved and recorded. In all, 90 patients were included in this study. The mean
      age was 48 +/- 18 years. The majority of the patients (54.4%) were male and 90%
      were on hemodialysis. The mean duration of dialysis was 8.0 +/- 5.0 years.
      Indications for PTX were symptomatic bone pain (95.6%), fractures (3.3%) and
      calciphylaxis (1.1%). Mean preoperative values for serum calcium, phosphate,
      alkaline phosphatase and intact parathyroid hormone (iPTH) were 2.40 +/-
      0.23mmol/L, 1.92 +/- 0.51 mmol/L, 689.60 +/- 708.50 U/L and 311.90 +/- 171.94
      pmol/L, respectively. The majority (92.2%) had all four glands removed and 92.2%
      of the glands showed hyperplasic changes. One year after PTX, 90 patients (100%)
      had serum iPTH <8 pmol/L and 28 patients (31%) had unmeasurable iPTH levels. A
      total of 15% of patients had hospitalizations for various reasons and of these,
      50% were within 90 days. The mean hospital stay was 14.4 +/- 18.6 days. The
      mortality rate was 4.4% and of these, 25% were in first 30 days. Causes of death
      were mainly from sepsis (75%) and acute coronary syndrome (25%). One patient
      (1.1%) had a relapse. Conclusions: Even though PTX markedly reduces postoperative
      serum iPTH levels, it carries with it significant risk of morbidity and
      mortality.

PMID- 29644070
TI  - Intravenous drug users who require dialysis: causes of renal failure and
      outcomes.
AB  - Background: Intravenous drug use is associated with progressive kidney disease of
      several aetiologies. It is associated with behavioural and lifestyle
      characteristics that make the provision of renal replacement therapies (RRTs)
      challenging. We observed that patients who use intravenous drugs [people who
      inject drugs (PWID)] present late to renal services and struggle to engage with
      treatment. We describe the experience of a UK centre providing renal services to
      a mixed city and rural population. Methods: A review of electronic patient
      records (2003-16) was performed to identify patients actively using intravenous
      drugs at the time of dialysis initiation. Descriptive statistics were used to
      describe aetiology, treatment, complications and prognosis. Results: Twenty-three
      patients were identified; 15 had a biopsy-proven diagnosis of AA amyloidosis. The
      median time from presentation to dialysis initiation was 47 days [interquartile
      range (IQR) 8-147.5]. Hepatitis C infection, venous thromboembolism and mental
      health disorders were common comorbidities. Eight patients attempted peritoneal
      dialysis; all failed after a median of 30 days (IQR 21.75-83). One-year survival
      was 65% (95% confidence interval 42-80), significantly lower than 2013 UK renal
      registry statistics for incident haemodialysis patients <65 years of age (94.2%).
      Conclusions: PWID who develop end-stage kidney disease in our region
      predominantly have AA amyloidosis. Most present late to renal services and have
      poor outcomes on all forms of RRT. Rates of transplantation are low. Management
      challenges include coexisting alcohol and mental health problems, low socio
      economic status, contamination of intravenous dialysis access and chaotic
      lifestyles. Multidisciplinary management with enhanced social support may be
      beneficial in improving outcomes for this patient group.

PMID- 29644071
TI  - Clinical management of patients on peritoneal dialysis in Italy: results from the
      ATENA study.
AB  - Background: In Italy, few studies have examined the clinical management of
      peritoneal dialysis (PD) patients, resulting in a lack of information and
      awareness. Methods: A total of 378 PD patients (64.7 +/- 14.3 years, 58.9% males)
      were enrolled across 15 centres in a 12-month retrospective and 6-month
      prospective study. The primary objective was to evaluate the achievement of
      Kidney Disease Outcomes Quality Initiative and Kidney Disease Improving Global
      Outcomes guidelines on recommended target values for anaemia, high blood pressure
      and mineral metabolism. Comorbidities, hospitalizations, treatment and quality of
      life were also assessed. Results: Frequent comorbidities included hypertension
      (87.8%) and cardiovascular disease (39.7%). Peritonitis was the leading cause of
      hospitalization [12 admissions per 100 person-years (95% confidence interval 9.3
      15.2)]. At 6 months, anaemia corrected by erythropoiesis-stimulating agents was
      observed in 30% of patients and 73% received erythropoiesis-stimulating agents.
      Systolic and diastolic blood pressures were recorded in 50% and 20% of patients,
      respectively. Sixty-four percent of echocardiograms revealed left ventricular
      hypertrophy and 30% of patients had vitamin D <10 ng/mL. Medication to treat
      intact parathyroid hormone (PTH) included calcitriol (36.3%), paricalcitol
      (29.2%), cholecalciferol (23.6%) and cinacalcet (21.5%). In a subgroup of
      patients matched for baseline PTH treated for 1 year, a significant reduction in
      PTH with paricalcitol (-41%; P < 0.001) but not cinacalcet (+2%; P = 0.63) was
      observed. Comparison of quality of life domains revealed significant differences
      for symptoms (P = 0.049), cognitive function (P = 0.019) and social support (P =
      0.04) (baseline versus 6 months). Conclusions: Hypertension and cardiovascular
      diseases were frequent comorbidities and peritonitis was the leading cause of
      hospitalization. Secondary hyperparathyroidism and anaemia were common, thus
      necessitating frequent monitoring of PTH, calcium, phosphorus and haemoglobin.

PMID- 29644072
TI  - Do kidney transplantations save money? A study using a before-after design and
      multiple register-based data from Sweden.
AB  - Background: The health care costs of kidney transplantation and dialysis are
      generally unknown. This study estimates the Swedish health care costs of kidney
      transplantation and dialysis over 10 years from a health care perspective.
      Method: A before-after design was used, in which the patients served as their own
      controls. Health care costs the year before transplantation were assumed to
      continue in the absence of a transplant and the cost savings was therefore
      calculated as the difference between the expected costs and the actual costs
      during the 10-year follow-up period. Factors associated with the size of the cost
      savings were studied using ordinary least-squares regression. Results: Altogether
      66-79% of the expected health care costs over 10 years were avoided through
      kidney transplantation, resulting in a cost savings of ?380 000 (2012 price-year)
      per patient. Savings were the highest for successful transplantations, but on
      average the treatment was cost-saving also for patients who returned to dialysis.
      No gender or age differences could be found, with the exception of a higher cost
      of transplantation for children and a generally higher cost for younger compared
      with older patients on dialysis. A negative association was also found between
      age at the time of transplantation and the size of the cost savings for the
      younger part of the sample. Conclusion: Kidney transplantations have led to
      substantial cost savings for the Swedish health care system. An increase in
      donated kidneys has the potential to further reduce the cost of renal replacement
      therapy.

PMID- 29644073
TI  - First UK case report of kidney transplantation from an HIV-infected deceased
      donor to two HIV-infected recipients.
AB  - Kidney transplantation is now considered the treatment of choice for many human
      immunodeficiency virus (HIV)-infected patients with end-stage renal disease
      (ESRD). Graft survival rates using HIV-negative donors and carefully selected HIV
      positive ESRD patients are similar to those observed in HIV-uninfected kidney
      transplant recipients. To address the relative shortfall in donated organs it has
      been proposed that organs from HIV-infected deceased donors might be allocated to
      HIV-infected patients on the transplant waiting list. Preliminary experience in
      South Africa reports promising short-term outcomes in a small number of HIV
      infected recipients of kidney transplants from HIV-infected donors. We sought to
      replicate this experience in the UK by accepting kidney offers from HIV infected
      deceased donors for patients with HIV-infection on the kidney transplant waiting
      list. Here we report the UK's first cases of kidney transplantation between HIV
      positive donors and recipients.

PMID- 29644074
TI  - Acquisition of pluripotency in the chick embryo occurs during intrauterine
      embryonic development via a unique transcriptional network.
AB  - Background: Acquisition of pluripotency by transcriptional regulatory factors is
      an initial developmental event that is required for regulation of cell fate and
      lineage specification during early embryonic development. The evolutionarily
      conserved core transcriptional factors regulating the pluripotency network in
      fishes, amphibians, and mammals have been elucidated. There are also species
      specific maternally inherited transcriptional factors and their intricate
      transcriptional networks important in the acquisition of pluripotency. In avian
      species, however, the core transcriptional network that governs the acquisition
      of pluripotency during early embryonic development is not well understood.
      Results: We found that chicken NANOG (cNANOG) was expressed in the stages between
      the pre-ovulatory follicle and oocyte and was continuously detected in Eyal
      Giladi and Kochav stage I (EGK.I) to X. However, cPOUV was not expressed during
      folliculogenesis, but began to be detectable between EGK.V and VI. Unexpectedly,
      cSOX2 could not be detected during folliculogenesis and intrauterine embryonic
      development. Instead of cSOX2, cSOX3 was maternally inherited and continuously
      expressed during chicken intrauterine development. In addition, we found that the
      pluripotency-related genes such as cENS-1, cKIT, cLIN28A, cMYC, cPRDM14, and
      cSALL4 began to be dramatically upregulated between EGK.VI and VIII. Conclusion:
      These results suggest that chickens have a unique pluripotent circuitry since
      maternally inherited cNANOG and cSOX3 may play an important role in the initial
      acquisition of pluripotency. Moreover, the acquisition of pluripotency in chicken
      embryos occurs at around EGK.VI to VIII.

PMID- 29644075
TI  - Regulation of amino acid transporters in the mammary gland from late pregnancy to
      peak lactation in the sow.
AB  - Background: Milk protein is crucial for milk quality in sows and health of
      newborn piglets. Plasma amino acids (AA) in sows are important precursors for
      milk protein synthesis in the mammary gland. In order to study the regulation of
      AA transported in sow mammary glands and possible underlying mechanisms, we
      measured the expression of genes coding for milk proteins, AA transporter
      expressions, and plasma AA concentrations in sows at three different
      physiological stages (D-17, D1 and D17 of lactation), and then further
      investigated the regulation of AA transport across the cell membrane by adaptive
      mechanisms using pig mammary epithelial cells (PMEC) as an in vitro model. PMEC
      were cultured in DMEM:F12 with 4 amino acid concentrations (0 * AA complex, 1 *
      AA complex, 5 * AA complex, and 25 * AA complex). Classes of AA complexes
      evaluated in this study included neutral AAs (L-Ala + L-Ser + L-Cys), acidic AAs
      (L-Asp, L-Glu) and neutral + basic AAs (L-Ala + L-Ser + L-Cys + L-Lys). Results:
      Our results indicated that mRNA expression of genes coding for milk protein
      (alphas1-casein, alphas2-casein, beta-casein and kappa-casein) increased
      significantly with the advance of physiological stage (P < 0.05), and plasma
      concentrations of most AAs including threonine, serine, glutamate, alanine,
      valine, cysteine, methionine, isoleucine and tyrosine were greater at D1 of
      lactation compared with D-17 and D17 of lactation (P < 0.05). Additionally,
      protein and gene expressions of AA transporters including excitatory AA
      transporter 3 (EAAT3), alanine/serine/cysteine/threonine transporter (ASCT1) and
      sodium-coupled neutral AA transporter 1 (SNAT2) were greater in lactating sow
      mammary glands compared with sow mammary glands in late pregnancy (P < 0.05). The
      mRNA expressions of SLC38A2, SLC1A1, SLC6A14 increased significantly in the cell
      mediums supplemented with 5 * and 25 * of AA complexes compared with those cells
      cultured in DMEM/F12 cell medium (P < 0.05). The mRNA expressions of SLC38A,
      SLC1A4, and SLC6A14 also increased in EBSS cell medium compared to DMEM/F12.
      However, only mRNA expression of SLC38A decreased when AA complex was added into
      EBSS (P < 0.05). Conclusion: AA transportation was positively regulated in sow
      mammary glands with the advance of physiological stage from late pregnancy to
      peak of lactation and AA transporters in PMECs were adaptively regulated by
      changed AA concentrations.

PMID- 29644077
TI  - Unusual presentation of pheochromocytoma: thirteen years of anxiety requiring
      psychiatric treatment.
AB  - : Pheochromocytoma is a rare tumor of the adrenal gland. It often presents with
      the classic triad of headache, palpitations and generalized sweating. Although
      not described as a typical symptom of pheochromocytoma, anxiety is the fourth
      most common symptom reported by patients suffering of pheochromocytoma. We report
      the case of a 64 year old man who had severe anxiety and panic disorder as
      presenting symptoms of pheochromocytoma. After 13 years of psychiatric follow-up,
      the patient was diagnosed with malignant pheochromocytoma. After surgical
      resection of his pheochromocytoma and his hepatic metastases, the major panic
      attacks completely disappeared, the anxiety symptoms improved significantly and
      the psychiatric medications were stopped except for a very low maintenance dose
      of venlafaxine. We found in our cohort of 160 patients with pheochromocytoma 2
      others cases of apparently benign tumors with severe anxiety that resolved after
      pheochromocytoma resection. These cases highlight that pheochromocytoma should be
      included in the differential diagnosis of refractory anxiety disorder. Learning
      points: Anxiety and panic disorder may be the main presenting symptoms of
      pheochromocytoma.The diagnosis of pheochromocytoma should be excluded in cases of
      long-term panic disorder refractory to medications since the anxiety may be
      secondary to a catecholamine-secreting tumor.Surgical treatment of
      pheochromocytoma leads to significant improvement of anxiety disorders.

PMID- 29644076
TI  - Lost in translation: The 3'-UTR of IGF1R as an ancient long noncoding RNA.
AB  - Background and objectives: The insulin-like growth factor (IGF) signaling system
      is a major arena of intragenomic conflict over embryonic growth between imprinted
      genes of maternal and paternal origin and the IGF type 1 receptor (IGF1R)
      promotes proliferation of many human cancers. The 3'-untranslated region (3'-UTR)
      of the mouse Igf1r mRNA is targeted by miR-675-3p derived from the imprinted H19
      long noncoding RNA. We undertook a comparative sequence analysis of vertebrate
      IGF1R 3'-UTRs to determine the evolutionary history of miR-675 target sequences
      and to identify conserved features that are likely to be involved in post
      transcriptional regulation of IGF1R translation. Methodology: Sequences of IGF1R
      3'-UTRs were obtained from public databases and analyzed using publicly available
      algorithms. Results: A very long 3'-UTR is a conserved feature of vertebrate
      IGF1R mRNAs. We found that some ancient microRNAs, such as let-7 and mir-182,
      have predicted binding sites that are conserved between cartilaginous fish and
      mammals. One very conserved region is targeted by multiple, maternally expressed
      imprinted microRNAs that appear to have evolved more recently than the targeted
      sequences. Conclusions and implications: The conserved structures we identify in
      the IGF1R 3'-UTR are strong candidates for regulating cell proliferation during
      development and carcinogenesis. These conserved structures are now targeted by
      multiple imprinted microRNAs. These observations emphasize the central importance
      of IGF signaling pathways in the mediation of intragenomic conflicts over
      embryonic growth and identify possible targets for therapeutic interventions in
      cancer.

PMID- 29644078
TI  - Increased risk of thyroid cancer in female residents nearby nuclear power plants
      in Korea: was it due to detection bias?
AB  - Background: The Korea Radiation Effect & Epidemiology Cohort - The resident
      cohort (KREEC-R) study concluded that there is no epidemiological or causal
      evidence supporting any increase in cancer risks resulting from radiation from
      Korean nuclear power plants (NPPs). But the risks of thyroid cancer in women were
      significantly higher in residents living near NPPs than control. Debate about the
      cause of the pattern of thyroid cancer incidence in women is ongoing and some
      researchers argue that detection bias influenced the result of KREEC-R study.
      Therefore there was a need to investigate whether residents living near NPPs who
      were assessed in the KREEC-R were actually tested more often for thyroid cancer.
      We evaluated the possibility of detection bias in the finding of the KREEC-R
      study based on materials available at this time. Methods: Using the KREEC-R raw
      data, we calculated age standardized rates (ASRs) of female thyroid cancer and re
      analyzed the results of survey on the use of medical services. We also marked the
      administrative districts of residents who received the Radiation Health Research
      Institute (RHRI) health examinations and those in which thyroid cancer case
      occurred as per the Chonnam National University Research Institute of Medical
      Sciences (RIMS) final report on maps where the locations of NPPs and 5 km-radii
      around them were also indicated. And we compared the incidence rates of Radiation
      induced cancer measured between the first period when RHRI health examinations
      were not yet implemented, and the second period when the RHRI health examinations
      were implemented. Results: The ASR for the far-distance group, which comprised
      residents living in areas outside the 30 km radius of the NPPs, increased rapidly
      after 2000; however, that of the exposed group, which comprised residents living
      within a 5 km radius of the NPPs, started to increase rapidly even before 1995.
      The frequencies of the use of medical services were significantly higher in the
      intermediate proximate group, which comprised residents living within a 5-30 km
      radius of the NPPs, than in the exposed group in women. In case of female thyroid
      cancer, the second period ASR was higher than the first period ASR, but in case
      of female liver cancer and female stomach cancer no significant difference were
      observed between the periods. On map, many administrative districts of residents
      who received RHRI health examinations and most administrative districts in which
      thyroid cancer case occurred on RIMS final report were outside 5 km-radii around
      NPPs. Conclusions: We could not find any evidence supporting the assertion that
      detection bias influenced the increased risks of female thyroid cancer observed
      in the exposed group of the KREEC-R study, as opposed to the control group.

PMID- 29644080
TI  - Safety, tolerability and pharmacokinetics of subcutaneous and intravenous
      anifrolumab in healthy volunteers.
AB  - Objectives: To compare the pharmacokinetics (PK), safety and tolerability of
      subcutaneous (SC) and intravenous anifrolumab, an anti-type I interferon receptor
      monoclonal antibody in development for SLE, in healthy volunteers. Methods: In
      this Phase I randomised, placebo-controlled study, 30 adults were assigned to
      three treatment cohorts (anifrolumab 300 mg SC (n=6), anifrolumab 300 mg
      intravenous (n=6), anifrolumab 600 mg SC (n=6)) and placebo (n=4/cohort). Serial
      blood samples were collected up to Day 84 to measure anifrolumab concentrations
      and antidrug antibodies (ADAs). PK parameters were estimated by noncompartmental
      analysis. Results: Maximum serum concentrations in SC cohorts occurred after 4-7
      days. Anifrolumab serum concentrations were below the limit of detection in all
      individuals by Day 84. Exposure to SC anifrolumab increased dose proportionally
      from 300 mg to 600 mg based on area under the serum concentration-time curve.
      Anifrolumab 300 mg SC exposure reached 87% of the intravenous exposure.
      Anifrolumab 300 mg SC and placebo administration elicited minimal injection-site
      reactions. Transient injection-site induration occurred in five of six
      individuals after anifrolumab 600 mg SC and two of four individuals after
      placebo. Transient, mild to moderate injection-site induration and pruritus
      occurred simultaneously in two of six individuals after anifrolumab 600 mg SC.
      Adverse events were reported by 50% (n=9) of anifrolumab-treated individuals and
      33% (n=4) of placebo-treated individuals. ADAs were detected in only one
      individual in the anifrolumab 300-mg intravenous group at the Day 84 assessment.
      Conclusion: Anifrolumab 300-mg SC exposure was 87% of intravenous administration,
      with single SC anifrolumab administrations well tolerated in healthy volunteers.

PMID- 29644081
TI  - Risk of adverse events from different drugs for SLE: a systematic review and
      network meta-analysis.
AB  - Objective: The comparative safety of immunosuppressive drugs, biologicals and
      glucocorticoids (GC) for patients with SLE remains controversial. We aimed to
      investigate the specific side effects of the available SLE drugs in this
      population of patients. Methods: Electronic databases were systematically
      searched through September 2017 for randomised trials in patients with SLE. The
      primary outcomes were all-cause mortality and withdrawal related to adverse
      events (AEs). We performed a random-effects network meta-analysis to obtain
      estimates for primary and secondary outcomes and presented these estimates as ORs
      with 95% CIs. Results: Forty-four studies comprising 9898 participants were
      included in the network meta-analysis. No drug regimen was considered to be safer
      for reducing all-cause mortality. However, compared with cyclophosphamide,
      azathioprine (OR 3.04, 95% CI (1.44 to 6.42)) and cyclosporine (OR 3.28, 95% CI
      (1.04 to 10.35)) were significantly less safety in AE-related withdrawals, and GC
      was ranked lowest and led to higher withdrawal rates. Tacrolimus (TAC) was ranked
      high and showed a benefit in many outcomes. Biologicals and chloroquine also
      showed good safety in all of the available outcomes, while the beneficial effects
      of other immunosuppressive drugs were not substantial in different types of
      serious adverse events. Conclusions: TAC is the safest strategy for patients with
      SLE. Biologicals and chloroquine are also fairly safe for patients with SLE. The
      use of other immunosuppressive drugs and GC needs to be balanced against the
      potential harms of different types of AEs, and the practical safety of drug
      combinations still requires further trials to evaluate.

PMID- 29644083
TI  - Acute interstitial pneumonia as first presentation of anti-synthetase syndrome:
      an atypical case.
AB  - Anti-synthetase syndrome is characterized by myositis associated with
      interstitial lung disease (ILD), the usual pattern of ILD being non-specific
      interstitial pneumonia type or usual interstitial pneumonia. We report a case of
      anti-synthetase syndrome presenting as acute interstitial pneumonia which is
      reported only once before. With this case, we emphasize the need to consider anti
      synthetase syndrome even in patients presenting with acute onset ILD. Physicians
      should raise their index of suspicion in this clinical context as timely
      diagnosis, early treatment, and a multidisciplinary approach is paramount for
      optimal care of these patients.

PMID- 29644082
TI  - Characterisation of anifrolumab, a fully human anti-interferon receptor
      antagonist antibody for the treatment of systemic lupus erythematosus.
AB  - Objective: We investigated the mechanistic and pharmacological properties of
      anifrolumab, a fully human, effector-null, anti-type I interferon (IFN) alpha
      receptor 1 (IFNAR1) monoclonal antibody in development for SLE. Methods: IFNAR1
      surface expression and internalisation on human monocytes before and after
      exposure to anifrolumab were assessed using confocal microscopy and flow
      cytometry. The effects of anifrolumab on type I IFN pathway activation were
      assessed using signal transducer and activator of transcription 1 (STAT1)
      phosphorylation, IFN-stimulated response element-luciferase reporter cell assays
      and type I IFN gene signature induction. The ability of anifrolumab to inhibit
      plasmacytoid dendritic cell (pDC) function and plasma cell differentiation was
      assessed by flow cytometry and ELISA. Effector-null properties of anifrolumab
      were assessed in antibody-dependent cell-mediated cytotoxicity (ADCC) and
      complement-dependent cytotoxicity (CDC) assays with B cells. Results: Anifrolumab
      reduced cell surface IFNAR1 by eliciting IFNAR1 internalisation. Anifrolumab
      blocked type I IFN-dependent STAT1 phosphorylation and IFN-dependent signalling
      induced by recombinant and pDC-derived type I IFNs and serum of patients with
      SLE. Anifrolumab suppressed type I IFN production by blocking the type I IFN
      autoamplification loop and inhibited proinflammatory cytokine induction and the
      upregulation of costimulatory molecules on stimulated pDCs. Blockade of IFNAR1
      suppressed plasma cell differentiation in pDC/B cell co-cultures. Anifrolumab did
      not exhibit CDC or ADCC activity. Conclusions: Anifrolumab potently inhibits type
      I IFN-dependent signalling, including the type I IFN autoamplification loop, and
      is a promising therapeutic for patients with SLE and other diseases that exhibit
      chronic dysfunctional type I IFN signalling.

PMID- 29644084
TI  - Primary microcephaly caused by novel compound heterozygous mutations in ASPM.
AB  - Autosomal recessive primary microcephaly (microcephaly primary hereditary, MCPH)
      is a genetically heterogeneous rare developmental disorder that is characterized
      by prenatal onset of abnormal brain growth, which leads to intellectual
      disability of variable severity. We report a 5-year-old male who presented with a
      severe form of primary microcephaly. Targeted panel sequencing revealed compound
      heterozygous truncating mutations of the abnormal spindle-like microcephaly
      associated (ASPM) gene, which confirmed the MCPH5 diagnosis. A novel NM_018136.4:
      c.9742_9745del (p.Lys3248Serfs*13) deletion mutation was identified.

PMID- 29644085
TI  - Protein molecular modeling shows residue T599 is critical to wild-type function
      of POLG and description of a novel variant associated with the SANDO phenotype.
AB  - Sensory ataxic neuropathy with dysarthria and ophthalmoparesis (SANDO) is a rare
      phenotype resulting from pathogenic variants of mitochondrial DNA polymerase
      gamma (POLG). We modeled a novel POLG variant, T599P, that causes the SANDO
      phenotype and another variant at the same residue, p.T599E, to observe their
      effect on protein function and confirm the pathogenicity of T599P. Through
      neoteric molecular modeling techniques, we show that changes at the T599 residue
      position introduce extra rigidity into the surrounding helix-loop-helix, which
      places steric pressure on nearby nucleotides. We also provide a clinical
      description of the T599P variant, which was found in a 42-year-old female
      proband. The proband presented a 1-year history of progressive gait instability,
      dysarthria and foot numbness. Her neurologic examination revealed ataxic
      dysarthria, restricted eye movements, head and palatal tremors, reduced lower
      limb reflexes, distal multimodal sensory loss and a wide, unsteady ataxic gait.
      Electromyography studies indicated a sensory neuropathy. Whole-exome sequencing
      was pursued after tests for infectious, inflammatory and paraneoplastic causes
      were negative.

PMID- 29644086
TI  - Is recreational running associated with earlier delivery and lower birth weight
      in women who continue to run during pregnancy? An international retrospective
      cohort study of running habits of 1293 female runners during pregnancy.
AB  - Background: Increasingly, women of reproductive age participate in recreational
      running, but its impact on pregnancy outcome is unknown. We investigated whether
      running affects gestational age at delivery and birth weight as indicators of
      cervical integrity and placental function, respectively. Methods: 1293 female
      participants were recruited from parkrun, which organises weekly runs involving
      1.25 million runners across 450 parks worldwide. Those under 16 or unable to
      provide outcome data were excluded. Women were categorised according to whether
      they continued to run during pregnancy or not. Those who continued were further
      stratified dependent on average weekly kilometres, and which trimester they ran
      until. Retrospectively collected primary outcomes were gestational age at
      delivery and birthweight centile. Other outcomes included assisted vaginal
      delivery rate and prematurity at clinically important gestations. Results: There
      was no significant difference in gestational age at delivery: 279.0 vs 279.6 days
      (mean difference 0.6 days, CI -1.3 to 2.4 days; P=0.55) or birthweight centile:
      46.9%vs 44.9% (mean difference 2.0%, CI -1.3% to -5.3%; P=0.22) in women who
      stopped running and those who continued, respectively. Assisted vaginal delivery
      rate was increased in women who ran: 195/714 (27%) vs 128/579 (22%) (OR 1.32; CI
      1.02 to 1.71; P=0.03). Conclusion: Continuing to run during pregnancy does not
      appear to affect gestational age or birthweight centile, regardless of mean
      weekly distance or stage of pregnancy. Assisted vaginal delivery rates were
      higher in women who ran, possibly due to increased pelvic floor muscle tone.
      Randomised prospective analysis is necessary to further explore these findings.

PMID- 29644087
TI  - Clinical observation of biomimetic mineralized collagen artificial bone putty for
      bone reconstruction of calcaneus fracture.
AB  - This study investigated clinical outcomes of biomimetic mineralized collagen
      artificial bone putty for bone reconstruction in the treatment of calcaneus
      fracture. Sixty cases of calcaneal fractures surgically treated with open
      reduction and internal fixation in our hospital from June 2014-2015 were chosen
      and randomly divided into two groups, including 30 cases treated with biomimetic
      mineralized collagen artificial bone putty as treatment group, and 30 cases
      treated with autogenous ilia as control group. The average follow-up time was
      17.2 +/- 3.0 months. The results showed that the surgery duration and
      postoperative drainage volume of treatment group were significantly lower than
      control group; there were no statistically significant differences in the
      fracture healing time, American Orthopaedic Foot and Ankle Society scores at 3
      and 12 months after surgery, Bohler's angle, Gissane's angle and height of
      calcaneus between the two groups. There were no significant differences in wound
      complication and reject reaction between the two groups, while significant
      difference in donor site complication. As a conclusion, the implantation of
      biomimetic mineralized collagen artificial bone putty in the open reduction of
      calcaneal fracture resulted in reliable effect and less complications, which is
      suitable for clinical applications in the treatment of bone defect in calcaneal
      fractures.

PMID- 29644088
TI  - Anti-biofilm and remineralization effects of chitosan hydrogel containing
      amelogenin-derived peptide on initial caries lesions.
AB  - In this study, we have designed a more clinically powerful anti-caries treatment
      by applying the amelogenin-derived peptide QP5 to the antibacterial carrier
      material chitosan in a hydrogel (CS-QP5 hydrogel), and characterized its effects
      on the inhibition of a cariogenic biofilm and the promotion of the
      remineralization of the initial caries lesions. The results indicated that the CS
      QP5 hydrogel sustainably inhibited the growth of the Streptococcus mutans
      biofilm, lactic acid production and the metabolic activity over a prolonged
      period of time. Moreover, the CS-QP5 hydrogel promoted the remineralization of
      early enamel lesions, which were indicated by surface micro-hardness (, polarized
      light microscopy and transverse microradiography. In conclusion, the CS-QP5
      hydrogel shows good potential for caries control in the clinic because of its
      antibacterial effects as well as the remineralization of initial enamel carious
      lesions even in a biofilm model over a prolonged period of time.

PMID- 29644089
TI  - Heterotopic bone formation in the musculus latissimus dorsi of sheep using beta
      tricalcium phosphate scaffolds: evaluation of different seeding techniques.
AB  - Osseous reconstruction of large bone defects remains a challenge in oral and
      maxillofacial surgery. In addition to autogenous bone grafts, which despite
      potential donor-site mobility still represent the gold standard in reconstructive
      surgery, many studies have investigated less invasive alternatives such as in
      vitro cultivation techniques. This study compared different types of seeding
      techniques on pure beta-tricalcium phosphate scaffolds in terms of bone formation
      and ceramic resorption in vivo. Cylindrical scaffolds loaded with autologous
      cancellous bone, venous blood, bone marrow aspirate concentrate or extracorporeal
      in vitro cultivated bone marrow stromal cells were cultured in sheep on a
      perforator vessel of the musculus latissimus dorsi over a 6-month period.
      Histological and histomorphometric analyses revealed that scaffolds loaded with
      cancellous bone were superior at promoting heterotopic bone formation and ceramic
      degradation, with autogenous bone and bone marrow aspirate concentrate inducing
      in vivo formation of vital bone tissue. These results confirm that autologous
      bone constitutes the preferred source of osteoinductive and osteogenic material
      that can reliably induce heterotopic bone formation in vivo.

PMID- 29644090
TI  - Human bone graft cytocompatibility with mesenchymal stromal cells is comparable
      after thermal sterilization and washing followed by gamma-irradiation: an in
      vitro study.
AB  - Human bone allografts present a better alternative to autografts in terms of
      minimization of the harvesting procedure complications. Prior to the use in
      clinical applications, they require sterilization which aims to reduce bioburden.
      This often comes at the expense of their biological properties as carriers of
      cells. In this study, we evaluated the cytocompatibility of human bone allografts
      processed and sterilized by three different methods with mesenchymal stromal
      cells. Bone morphology, biological and biochemical properties of the extracted
      bone-conditioned medium and viability of cells were assessed. We found that
      chemical sterilization had a strong negative effect on cell viability, whereas
      thermal sterilization and washing with subsequent gamma-irradiation both resulted
      in a bone graft compatible with the progenitor cells. Moreover, washing of the
      bone prior to sterilization allowed solid removal of cell debris and other bone
      marrow components. Taken together, our findings demonstrate the importance of a
      proper choice of the bone graft processing method for the production of the
      biomaterial suitable for tissue engineering.

PMID- 29644091
TI  - Comparison of the osteogenic capability of rat bone mesenchymal stem cells on
      collagen, collagen/hydroxyapatite, hydroxyapatite and biphasic calcium phosphate.
AB  - Collagen (COL), collagen/hydroxyapatite (COL/HA), HA and biphasic calcium
      phosphate were prepared as representative bone grafting materials with
      composition analogous to bone, and their structural characteristics were
      analyzed. The rat bone mesenchymal stem cells (BMSCs) were further seeded onto
      four groups of materials, and BMSCs grown in basic medium and standard osteogenic
      medium were set as controls of a reference model to show the basic and osteogenic
      behavior of cells without the intervention of materials. Cellular behaviors were
      characterized, including proliferation, spreading morphology and expression of
      osteogenesis factors. The rat BMSCs proliferated properly with time on four
      groups of materials as well on two groups of controls, and typical cuboidal,
      polygonal and extremely-elongated morphologies of cells were observed. According
      to the real-time polymerase chain reaction data, a higher osteogenic gene
      expression level was dependent upon the growing morphology but not the
      proliferation rate of cells, and the osteogenic differentiation capacity of cells
      onto four groups of materials varied in specific genes. In general, BMSCs
      exhibited the highest osteogenic capacity onto COL/HA, but the poorest onto HA.
      The growing behaviors of cells on materials were further discussed in comparison
      with the cases of OC and BC of the reference model. The present attempt to
      comparatively analyze cell experimental data with a reference model is expected
      to be useful for revealing the difference in the osteogenic capability of MSCs
      onto materials or even the bioactivity of materials.

PMID- 29644092
TI  - The grafts modified by heparinization and catalytic nitric oxide generation used
      for vascular implantation in rats.
AB  - Small-diameter (<6 mm) vascular grafts are increasingly needed in peripheral
      vascular surgery but have few successes because of acute thrombosis, incomplete
      endothelialization and intimal hyperplasia after implantation. This study used
      electrospun poly(epsilon-caprolactone) as the matrix material. Heparin and
      selenium-containing catalyst-organoselenium modified polyethyleneimine were
      introduced through layer-by-layer assembly in order to build a vascular graft
      with in situ nitric oxide (NO) generation. The aim of this study was to explore
      the application of the graft with improved histocompatibility and biological
      function for vascular implantation in rats. After implantation in rats, compared
      to poly(epsilon-caprolactone), the modified grafts could promote the adhesion and
      proliferation of endothelial cells, and inhibit the adhesion of smooth muscle
      cells. The modified grafts remarkably promoted endothelialization, inhibited
      intimal hyperplasia and increased the ratio of alternatively activated
      macrophages (M2) to classical activated macrophages (M1). This work constructed a
      vascular graft with heparinization and catalytic NO generation for improving the
      vascularization, and accelerating the tissue regeneration by regulating the
      inflammatory response. The present study indicates that it is a promising method
      for regulating response and tissue regeneration of small diameter vascular grafts
      by a novel approach of combining heparinization and catalytic NO generation.

PMID- 29644093
TI  - Effect of microporosity on scaffolds for bone tissue engineering.
AB  - Microporosity has a critical role in improving the osteogenesis of scaffolds for
      bone tissue engineering. Although the exact mechanism, by which it promotes new
      bone formation, is not well recognized yet, the related hypothesis can be found
      in many previous studies. This review presents those possible mechanisms about
      how the microporosity enhances the osteogenic-related functions of cells in vitro
      and the osteogenic activity of scaffolds in vivo. In summary, the increased
      specific surface areas by microporosity can offer more protein adsorption sites
      and accelerate the release of degradation products, which facilitate the
      interactions between scaffolds and cells. Meanwhile, the unique surface
      properties of microporous scaffolds have a considerable effect on the protein
      adsorption. Moreover, capillary force generated by the microporosity can improve
      the attachment of bone-related cells on the scaffolds surface, and even make the
      cells achieve penetration into the micropores smaller than them. This review also
      pays attention to the relationship between the biological and mechanical
      properties of microporous scaffolds. Although lots of achievements have been
      obtained, there is still a lot of work to do, some of which has been proposed in
      the conclusions and perspectives part.

PMID- 29644094
TI  - Insufficiency of DNA repair enzyme ATM promotes naive CD4 T-cell loss in chronic
      hepatitis C virus infection.
AB  - T cells have a crucial role in viral clearance and vaccine response; however, the
      mechanisms regulating their responses to viral infections or vaccinations remain
      elusive. In this study, we investigated T-cell homeostasis, apoptosis, DNA
      damage, and repair machineries in a large cohort of subjects with hepatitis C
      virus (HCV) infection. We found that naive CD4 T cells in chronically HCV
      infected individuals (HCV T cells) were significantly reduced compared with age
      matched healthy subjects. In addition, HCV T cells were prone to apoptosis and
      DNA damage, as evidenced by increased 8-oxoguanine expression and gammaH2AX/53BP1
      formed DNA damage foci-hallmarks of DNA damage responses. Mechanistically, the
      activation of DNA repair enzyme ataxia telangiectasia mutated (ATM) was dampened
      in HCV T cells. ATM activation was also diminished in healthy T cells exposed to
      ATM inhibitor or to HCV (core protein) that inhibits the phosphoinositide 3
      kinase pathway, mimicking the biological effects in HCV T cells. Importantly,
      ectopic expression of ATM was sufficient to repair the DNA damage, survival
      deficit, and cell dysfunctions in HCV T cells. Our results demonstrate that
      insufficient DNA repair enzyme ATM leads to increased DNA damage and renders HCV
      T cells prone to apoptotic death, which contribute to the loss of naive T cells
      in HCV infection. Our study reveals a novel mechanism for T-cell dysregulation
      and viral persistence, providing a new strategy to improve immunotherapy and
      vaccine responses against human viral diseases.

PMID- 29644095
TI  - Rapid whole-genome sequencing decreases infant morbidity and cost of
      hospitalization.
AB  - Genetic disorders are a leading cause of morbidity and mortality in infants.
      Rapid whole-genome sequencing (rWGS) can diagnose genetic disorders in time to
      change acute medical or surgical management (clinical utility) and improve
      outcomes in acutely ill infants. We report a retrospective cohort study of
      acutely ill inpatient infants in a regional children's hospital from July 2016
      March 2017. Forty-two families received rWGS for etiologic diagnosis of genetic
      disorders. Probands also received standard genetic testing as clinically
      indicated. Primary end-points were rate of diagnosis, clinical utility, and
      healthcare utilization. The latter was modelled in six infants by comparing
      actual utilization with matched historical controls and/or counterfactual
      utilization had rWGS been performed at different time points. The diagnostic
      sensitivity of rWGS was 43% (eighteen of 42 infants) and 10% (four of 42 infants)
      for standard genetic tests (P = .0005). The rate of clinical utility of rWGS
      (31%, thirteen of 42 infants) was significantly greater than for standard genetic
      tests (2%, one of 42; P = .0015). Eleven (26%) infants with diagnostic rWGS
      avoided morbidity, one had a 43% reduction in likelihood of mortality, and one
      started palliative care. In six of the eleven infants, the changes in management
      reduced inpatient cost by $800,000-$2,000,000. These findings replicate a prior
      study of the clinical utility of rWGS in acutely ill inpatient infants, and
      demonstrate improved outcomes and net healthcare savings. rWGS merits
      consideration as a first tier test in this setting.

PMID- 29644096
TI  - Cameroonian fruit bats harbor divergent viruses, including rotavirus H,
      bastroviruses, and picobirnaviruses using an alternative genetic code.
AB  - Most human emerging infectious diseases originate from wildlife and bats are a
      major reservoir of viruses, a few of which have been highly pathogenic to humans.
      In some regions of Cameroon, bats are hunted and eaten as a delicacy. This close
      proximity between human and bats provides ample opportunity for zoonotic events.
      To elucidate the viral diversity of Cameroonian fruit bats, we collected and
      metagenomically screened eighty-seven fecal samples of Eidolon helvum and
      Epomophorus gambianus fruit bats. The results showed a plethora of known and
      novel viruses. Phylogenetic analyses of the eleven gene segments of the first
      complete bat rotavirus H genome, showed clearly separated clusters of human,
      porcine, and bat rotavirus H strains, not indicating any recent interspecies
      transmission events. Additionally, we identified and analyzed a bat bastrovirus
      genome (a novel group of recently described viruses, related to astroviruses and
      hepatitis E viruses), confirming their recombinant nature, and provide further
      evidence of additional recombination events among bat bastroviruses.
      Interestingly, picobirnavirus-like RNA-dependent RNA polymerase gene segments
      were identified using an alternative mitochondrial genetic code, and further
      principal component analyses suggested that they may have a similar lifestyle to
      mitoviruses, a group of virus-like elements known to infect the mitochondria of
      fungi. Although identified bat coronavirus, parvovirus, and cyclovirus strains
      belong to established genera, most of the identified partitiviruses and
      densoviruses constitute putative novel genera in their respective families.
      Finally, the results of the phage community analyses of these bats indicate a
      very diverse geographically distinct bat phage population, probably reflecting
      different diets and gut bacterial ecosystems.

PMID- 29644097
TI  - The virome of Drosophila suzukii, an invasive pest of soft fruit.
AB  - Drosophila suzukii (Matsumura) is one of the most damaging and costly pests to
      invade temperate horticultural regions in recent history. Conventional control of
      this pest is challenging, and an environmentally benign microbial biopesticide is
      highly desirable. A thorough exploration of the pathogens infecting this pest is
      not only the first step on the road to the development of an effective
      biopesticide, but also provides a valuable comparative dataset for the study of
      viruses in the model family Drosophilidae. Here we use a metatransciptomic
      approach to identify viruses infecting this fly in both its native (Japanese) and
      invasive (British and French) ranges. We describe eighteen new RNA viruses,
      including members of the Picornavirales, Mononegavirales, Bunyavirales,
      Chuviruses, Nodaviridae, Tombusviridae, Reoviridae, and Nidovirales, and discuss
      their phylogenetic relationships with previously known viruses. We also detect 18
      previously described viruses of other Drosophila species that appear to be
      associated with D. suzukii in the wild.

PMID- 29644099
TI  - Dartos reflex as autonomic assessment in persons with spinal cord injury.
AB  - Study design: Prospective clinical series. Objectives: The dartos reflex (DR)
      produces unilateral elevation of the testis with vermicular contraction of the
      scrotal skin and penile retraction. It is a somato-autonomic reflex that depends
      on the T11-L2 sympathetic segment. Its presence was analysed in men with various
      levels and severities of spinal cord injury (SCI). Setting: France. Methods: Male
      patients with SCI undergoing urodynamic or sexual assessment were included. DR of
      the scrotum and penis were systematically assessed in addition to the usual
      neurological examination that included assessment of the autonomic system,
      cremaster, and sacral reflexes. The DR was evoked by applying a small ice pack on
      the scrotum, separately to each side. Results: Forty-six patients were assessed.
      DRs were always present when the T11-L2 segment was intact above the lesion (low
      paraplegia below L2) or below the lesion in an upper motor neuron (UMN) syndrome
      (spastic paraplegia above T10). They were more pronounced in the case of UMN
      syndrome. In the case of lower motor neuron (LMN) syndrome that included the T11
      L2 segment, DRs disappeared in all but one patient. Patients with a LMN lesion
      were more prone to retrograde or absent ejaculation, loss of psychogenic
      erection, and open bladder neck. Conclusions: The DR is a valuable test for the
      assessment of the integrity and excitability of the T11-L2 spinal segment. It is
      easy to perform and is predictive of some aspects of sexual and bladder neck
      function in men. DR should be considered as an addition to the autonomic
      standards.

PMID- 29644100
TI  - Persistent urine leakage around a suprapubic catheter: the experience of a person
      with chronic tetraplegia.
AB  - Introduction: Persistent urine leakage after suprapubic cystostomy in tetraplegic
      subjects occurs due to shrinkage of the urinary bladder and bladder spasms. The
      patient's social life is adversely affected as clothes become wet, smelly, and
      require frequent changing, thus increasing the workload of carers. Case
      presentation: A 48-year-old male sustained C-4 complete (AIS:A) tetraplegia while
      swimming in 2007. Suprapubic cystostomy was performed in 2009. From 2012, this
      patient had urine leakage around the suprapubic catheter, which became
      progressively more frequent. Propiverine, then oxybutynin tablets instead of
      propiverine, oxybutynin transdermal patches, and mirabegron in addition to
      oxybutynin were tried. An indwelling urethral catheter was used in addition to
      the suprapubic catheter to alleviate urine leakage when the bladder was
      undergoing spasms. This patient continued to have leakage around the suprapubic
      catheter. Leakage of urine was occasionally accompanied by autonomic dysreflexia.
      Leakage of urine caused huge amounts of extra work for carers, and family.
      Furthermore, leakage of urine had a significant impact on quality of life, and
      going out with friends and family. Bladder wall injection of Botox was performed
      in 2015 and in 2016, which reduced urine leakage. Discussion: Bladder wall
      injection of Botox to treat persistent urine leakage around the suprapubic
      catheter in spinal cord injury patients with suprapubic cystostomy has not been
      mentioned in NICE guidelines or publications indexed in PubMed. While
      recommending suprapubic cystostomy to subjects with tetraplegia, leakage of urine
      around the suprapubic catheter, which may occur sometime after suprapubic
      cystostomy, should be included in the conversation so that patients and carers
      become aware of this potential complication.

PMID- 29644098
TI  - Hydrogel-based scaffolds to support intrathecal stem cell transplantation as a
      gateway to the spinal cord: clinical needs, biomaterials, and imaging
      technologies.
AB  - The prospects for cell replacement in spinal cord diseases are impeded by
      inefficient stem cell delivery. The deep location of the spinal cord and complex
      surgical access, as well as densely packed vital structures, question the
      feasibility of the widespread use of multiple spinal cord punctures to inject
      stem cells. Disorders characterized by disseminated pathology are particularly
      appealing for the distribution of cells globally throughout the spinal cord in a
      minimally invasive fashion. The intrathecal space, with access to a relatively
      large surface area along the spinal cord, is an attractive route for global stem
      cell delivery, and, indeed, is highly promising, but the success of this approach
      relies on the ability of cells (1) to survive in the cerebrospinal fluid (CSF),
      (2) to adhere to the spinal cord surface, and (3) to migrate, ultimately, into
      the parenchyma. Intrathecal infusion of cell suspension, however, has been
      insufficient and we postulate that embedding transplanted cells within hydrogel
      scaffolds will facilitate reaching these goals. In this review, we focus on
      practical considerations that render the intrathecal approach clinically viable,
      and then discuss the characteristics of various biomaterials that are suitable to
      serve as scaffolds. We also propose strategies to modulate the local
      microenvironment with nanoparticle carriers to improve the functionality of
      cellular grafts. Finally, we provide an overview of imaging modalities for in
      vivo monitoring and characterization of biomaterials and stem cells. This
      comprehensive review should serve as a guide for those planning preclinical and
      clinical studies on intrathecal stem cell transplantation.

PMID- 29644101
TI  - Spinal cord injury epidemiological profile in the Sarah Network of Rehabilitation
      Hospitals-a Brazilian population sample.
AB  - Study design: Retrospective cross-sectional study. Objective: To describe the
      epidemiological profile of individuals with spinal cord injury (SCI), who visited
      the Sarah Network in 2014. Setting: Brazil, Brasilia-Federal District. Methods: A
      review of the electronic medical records of persons with SCI, aged over 15 years,
      was carried out. Results: The medical records of 2076 persons were evaluated: 83%
      were male, the mean age was 31 years, 40% did not complete elementary school,
      67.7% had paraplegia, and 74.4% had complete SCI. The primary etiologies were
      gunshot wounds (28.4%), motorcycle accidents (24.6%), and motor vehicle accidents
      (19.1%). In the comparative analysis between genders, differences were observed
      regarding the level of education and completeness of injury. Conclusion: Gunshot
      wounds were the main cause of SCI in our population, comprising mostly male
      individuals with thoracic injury, resulting in complete SCI. Data show a high
      incidence of SCI in young adults owing to violence in Brazil.

PMID- 29644102
TI  - Extrapolation concept at work with biosimilar: a decade of experience in
      oncology.

PMID- 29644103
TI  - Morphometric study of the semitendinosus muscle and its neurovascular pedicles in
      South Indian cadavers.
AB  - The purpose of this study was to determine the length of the semitendinosus
      muscle belly and its tendon in South Indian population and to study the
      topography and diameter of its neurovascular pedicles. The study included 46
      formalin fixed human cadaveric lower limbs. The length of the semitendinosus
      muscle belly and its tendon were measured. The neurovascular pedicles of the
      semitendinosus muscle were identified and counted. The diameter of the
      neurovascular pedicle was measured just before its entrance into the
      semitendinosus muscle. The topographical distance of the neurovascular pedicles
      from the origin of the semitendinosus muscle were determined. The mean length of
      the semitendinosus muscle belly was 332.3+/-36.1 mm and its tendon measured
      154.8+/-31.9 mm. The mean diameter of the vascular pedicle was measuring 11.4+/
      9.1 mm, just before its entrance into the semitendinosus muscle. The
      neurovascular pedicles, of the semitendinosus muscle were ranging between 1 and
      7. The distance of the entrance of neurovascular pedicle to the semitendinosus
      muscle from its origin was ranging between 46 and 272 mm. It was observed that
      the neurovascular pedicles were highest (31%) at the range of 151-200 mm away
      from the ischial tuberosity. The morphometric data obtained in the present study
      is enlightening to the orthopedic and plastic surgeons. The topographical
      knowledge of the neurovascular pedicles has its implications during the
      harvesting of the grafts and pedicle flaps. The diameter of vessels in the
      pedicles is enlightening because of new method of anterior cruciate ligament
      reconstruction.

PMID- 29644104
TI  - Homepage to distribute the anatomy learning contents including Visible Korean
      products, comics, and books.
AB  - The authors have operated the homepage (http://anatomy.co.kr) to provide the
      learning contents of anatomy. From the homepage, sectioned images, volume models,
      and surface models-all Visible Korean products-can be downloaded. The realistic
      images can be interactively manipulated, which will give rise to the interest in
      anatomy. The various anatomy comics (learning comics, comic strips, plastination
      comics, etc.) are approachable. Visitors can obtain the regional anatomy book
      with concise contents, mnemonics, and schematics as well as the simplified
      dissection manual and the pleasant anatomy essay. Medical students, health allied
      professional students, and even laypeople are expected to utilize the easy and
      comforting anatomy contents. It is hoped that other anatomists successively
      produce and distribute their own informative contents.

PMID- 29644105
TI  - Drawing method can improve musculoskeletal anatomy comprehension in medical
      faculty student.
AB  - The Chinese philosophy of Confucianism said "What I heard I forgot, what I see, I
      remember, what I do, I understand." During this time, most of the teaching and
      learning process relies on viewing and listening modalities only. As a result,
      much information does not last long in memory as well as the material
      understanding achieves became less deep. In studying anatomy science, drawing is
      one of effective important methods because it is an integration of ideas and
      knowledge of vision thereby increasing comprehension and learning motivation of
      college students. The purpose of this research is to know the musculoskeletal
      anatomy comprehension by drawing learning method in Medical Faculty student. This
      research uses observational analytic design with the cross-sectional design.
      Total sampling was done to the entire student of Physiotherapy Study Program in
      2012, 2013, and 2014, Medical Faculty of Udayana University. The average value of
      musculoskeletal anatomy of the student in 2012, 2013, and 2014 sequentially are
      31.67, 33.57, and 45.00, respectively. Normality test with Shapiro-Wilk and
      homogeneity with Levene's test showed normal results and homogeneous. One-way
      ANOVA test between groups showed a significant result that is 11.00 (P<0.05). It
      is concluded that the drawing method can improve the musculoskeletal anatomy
      comprehension in Medical Faculty student.

PMID- 29644106
TI  - Supraorbital nerve exits: positional variations and localization relative to
      surgical landmarks.
AB  - Significant variations exist in the occurrence, form, and position of
      supraorbital nerve exits through the frontal bone. Detailed knowledge of the
      positional variations of supraorbital exits is important to ensure safe and
      successful regional anesthesia, and to avoid iatrogenic nerve injuries during
      surgery of the orbitofacial region. Supraorbital nerve exits from 116 sides of 58
      dry intact adult skulls (37 male and 21 female) in a Sri Lankan population were
      examined to determine the morphological features and the precise position in
      relation to the facial midline, temporal crest of frontal bone, and
      frontozygomatic suture. A majority of supraorbital nerve exits existed as notches
      (73.8%) and the rest as foramina (26.2%). Accessory exits were seen in 18.9%
      skulls. Of the skulls examined, 55.1% displayed bilateral supraorbital notches,
      8.6% had bilateral supraorbital foramina, and 36.3% had a notch on one side and a
      foramen on the contralateral side. In males, the supraorbital nerve exit was
      located 23.64+/-3.49 mm laterally from the facial midline, 27.86+/-2.76 mm
      medially from the temporal crest of the frontal bone, 28.66+/-2.56 mm from the
      frontozygomatic suture, and 2.12+/-1.07 mm above the supraorbital margin in the
      case of a foramen, and in females 22.69+/-3.28 mm laterally from the facial
      midline, 26.32+/-3.02 medially from temporal crest of frontal bone, 27.29+/-3.05
      from the frontozygomatic suture, and 2.99+/-1.49 mm above the supraorbital margin
      when it existed as a foramen. The observations made in this study will be useful
      when planning a supraorbital nerve block and surgery in the supraorbital region.

PMID- 29644107
TI  - Cranial index in a modern people of Thai ancestry.
AB  - The present research aims to examine the cranial index in a modern people of Thai
      ancestry. Ultimately, this study will help to create a databank containing a
      cranial index for the classifications of the people from Asia. In this study, 185
      modern crania of people of supposed Thai ancestry were examined. They were
      collected from the Department of Anatomy at Chulalongkorn University in Bangkok,
      Thailand. The maximum cranial length and breadth were measured using standard
      anthropometric instruments based on Martin's methods. The cranial index was
      calculated using the equation ([maximum cranial breadth/maximum cranial
      length]*100). The mean cranial indices for the male and female skulls examined
      were 81.81+/-4.23 and 82.99+/-4.37, respectively. The most common type of skull
      in the modern Thai people in this study was the brachycranic type with a
      frequency of 42.7%, followed by the mesocranic (27.03%) and hyperbrachycranic
      types (25.59%). The rarest type observed in this study was the dolichocranic type
      (4.32%). The present study provides valuable data pertaining to the cranial index
      in a modern Thai population and reveals that modern Thai males and females belong
      to the brachycranic group. The results of this study will be of forensic
      anthropological importance to populations in close proximity to the location
      where the skulls studied here were sourced.

PMID- 29644108
TI  - Nutrition and growth: assessing the impact of regional nutritional intake on
      childhood development and metacarpal parameters.
AB  - Measuring skeletal development throughout juvenile growth can provide a greater
      understanding into the health, hormonal function and genetics of children. The
      metacarpals have been of interest for their potential to provide insights into
      healthy juvenile skeletal development. This study investigated the growth
      patterns of developing females from isolated communities who had varied diets.
      Anthropometrical measurements and hand-wrist X-rays were taken of 353 juvenile
      females from three populations: Pari Coastal Village and Bundi Highlands Village,
      Papua New Guinea (PNG); and Brisbane, Australia between 1968 to 1983. Radiographs
      were digitized, and the length and width of the second and third metacarpals
      compared to each subject's height and weight. As subject heights increased,
      metacarpal length and width increased. However, stature and second metacarpal
      length indicated the strongest correlation (P<0.01), compared to third metacarpal
      length (P<0.01) or width. From 11 to 13 years of age, Brisbane subjects were
      significantly heavier and taller in comparison to subjects from PNG, and coastal
      females were heavier and taller than the highland females. A prominent difference
      between the two PNG populations was the regional intake of protein in their
      diets. The second metacarpal presents particularly accurate measurements when
      determining the height or development of a child. Nutritional intake appears to
      have a major influence normal childhood growth, with a potential for protein
      deficiency to strongly inhibit growth. Any delayed growth is particularly evident
      in the child's stature, as well as in the development of the metacarpal long
      bones of the hand.

PMID- 29644109
TI  - Morphine-alcohol treatment impairs cognitive functions and increases neuro
      inflammatory responses in the medial prefrontal cortex of juvenile male rats.
AB  - In the developed and developing world, opioid consumption in combination with
      alcohol has become one of the substances abused. In this experiment, we examined
      the effects of alcohol, morphine, and morphine+alcohol combination on cognitive
      functions and neuroinflammatory responses in the medial prefrontal cortex (mPFC)
      of juvenile male rats. Alcohol (1.0 ml of 15% v/v ethanol twice daily,
      subcutaneously, 7 hours apart), morphine (0.5 ml/kg of 0.4 mg/kg morphine
      chlorate twice daily, subcutaneously, 7 hours apart), morphine+alcohol co
      treatment (0.5 ml/kg of 0.4 mg/kg morphine chlorate+1.0 ml of 15% v/v ethanol
      twice daily, subcutaneously, 7 hours apart) were administered for 21 days.
      Treatment with morphine+alcohol significantly impairs cognition functions in the
      Morris water maze, passive avoidance, and novel object recognition tests,
      furthermore, the treatment significantly increased the quantitative count of
      astrocytic cells and also conferred marked neuronal cell death in the mPFC, which
      were studied by glial fibrillary acidic protein immunochemistry for astrocytes
      and Cresyl violet for Nissl's substance distribution in neurons respectively.
      These results suggest that alcohol, morphine, and morphine+alcohol co-treatment
      may trigger cognitive deficits and neuroinflammatory responses in the brain.

PMID- 29644110
TI  - Ameliorative effect of vitamin B12 on seminiferous epithelium of cimetidine
      treated rats: a histopathological, immunohistochemical and ultrastructural study.
AB  - Cimetidine is an H2 receptor antagonist that has an antiandrogenic effect. It
      intervenes with the conversion of testosterone into estrogen in the Sertoli cells
      with accompanying testicular structural changes. In the present study, the
      microscopic and the ultrastructural changes induced by cimetidine and the effect
      of vitamin B12 as a protective agent on rat testes were studied. Immunoexpression
      of estrogen receptor beta (ERbeta) in testes was evaluated. Twenty-four adult
      male rats were divided into four groups: control, cimetidine-treated, vitamin B12
      treated, and combined cimetidine and vitamin B12 treated. The experimental rats
      were administered with cimetidine and/or vitamin B12 for 52 days. Group II rats
      showed marked atrophy of the seminiferous tubules with a significant increase in
      tubular diameter and decrease in the tubular luminal and epithelial areas.
      Ultrastructure of this group showed irregular Sertoli cells with basal
      cytoplasmic vacuolation and significantly thickened basement membrane. ERbeta
      immunoexpression was similar to controls. Group III rats showed near normal
      seminiferous tubular structures with minimal cellular alterations and the
      immunoreactivity of the testicular sections was very close to normal. However,
      group IV rats showed markedly immunopositive detached cells, spermatids, and
      primary spermatocytes. Cimetidine interferes with the control of spermatogenesis
      as evidenced by microscopic and ultrastructural studies and affection of ERbeta
      receptors and vitamin B12 has a protective action against this harmful effect.

PMID- 29644111
TI  - A rare combined variation of the coeliac trunk, renal and testicular vasculature.
AB  - The authors report a rare variation of the coeliac trunk, renal and testicular
      vasculature in a 27-year-old male cadaver. In the present case, the coeliac trunk
      and superior mesenteric artery was replaced by a modified coeliacomesenteric
      trunk formed by hepato-gastric and superior mesenteric arteries. Here the hepato
      gastric artery or trunk contributed towards the total hepatic inflow as well as a
      gastro-duodenal artery. A separate right gastric artery and an additional
      superior pancreatico-duodenal artery was also found in addition with a retro
      aortic left renal vein and a bilateral double renal arterial supply. The
      aforementioned coeliac trunk variation, to our knowledge, has never been reported
      before and this variation combined with the renal vasculature requires careful
      surgical consideration.

PMID- 29644112
TI  - Unusual bilateral sensory innervation of the dorsum of hand by lateral
      antebrachial cutaneous nerve: a case report.
AB  - A 68-year-old male cadaver showed bilateral variation in the sensory innervation
      of the dorsum of hand. On the dorsum of right hand, first digit and lateral half
      of second digit were supplied by lateral antebrachial cutaneous nerve (LABCN);
      medial side of second digit and lateral side of third digit were supplied by
      superficial branch of radial nerve (SBRN) and medial side of third digit, the
      fourth and fifth digits were supplied by dorsal cutaneous branch of ulnar nerve
      (DBUN). On the dorsum of the left hand, lateral side of first digit was supplied
      by LABCN, medial side of first digit, the second and third digits as well as the
      lateral side of fourth digit were supplied by SBRN; medial side of fourth digit
      and fifth digit were supplied by DBUN. These variations would be helpful in
      understanding peripheral neuropathy, in interpretation of conduction velocity
      studies and in reconstructive surgery of hand.

PMID- 29644113
TI  - Analysis of monitored ground support and rock mass response in a longwall
      tailgate entry.
AB  - A comprehensive monitoring program was conducted to measure the rock mass
      displacements, support response, and stress changes at a longwall tailgate entry
      in West Virginia. Monitoring was initiated a few days after development of the
      gateroad entries and continued during passage of the longwall panels on both
      sides of the entry. Monitoring included overcore stress measurements of the
      initial stress within the rock mass, changes in cable bolt loading, standing
      support pressure, roof deformation, rib deformation, stress changes in the coal
      pillar, and changes in the full three-dimensional stress tensor within the rock
      mass at six locations around the monitoring site. During the passage of the first
      longwall, stress measurements in the rock and coal detected minor changes in
      loading while minor changes were detected in roof deformation. As a result of the
      relatively favorable stress and geological conditions, the support systems did
      not experience severe loading or rock deformation until the second panel
      approached within 10-15 m of the instrumented locations. After reaching the peak
      loading at about 50-75 mm of roof sag, the cable bolts started to unload, and
      load was transferred to the standing supports. The standing support system was
      able to maintain an adequate opening inby the shields to provide ventilation to
      the first crosscut inby the face, as designed. The results were used to calibrate
      modeled cable bolt response to field data, and to validate numerical modeling
      procedures that have been developed to evaluate entry support systems. It is
      concluded that the support system was more than adequate to control the roof of
      the tailgate up to the longwall face location. The monitoring results have
      provided valuable data for the development and validation of support design
      strategies for longwall tailgate entries.

PMID- 29644114
TI  - Super enhancer inhibitors suppress MYC driven transcriptional amplification and
      tumor progression in osteosarcoma.
AB  - Osteosarcoma is the most common primary bone sarcoma that mostly occurs in young
      adults. The causes of osteosarcoma are heterogeneous and still not fully
      understood. Identification of novel, important oncogenic factors in osteosarcoma
      and development of better, effective therapeutic approaches are in urgent need
      for better treatment of osteosarcoma patients. In this study, we uncovered that
      the oncogene MYC is significantly upregulated in metastastic osteosarcoma
      samples. In addition, high MYC expression is associated with poor survival of
      osteosarcoma patients. Analysis of MYC targets in osteosarcoma revealed that most
      of the osteosarcoma super enhancer genes are bound by MYC. Treatment of
      osteosarcoma cells with super enhancer inhibitors THZ1 and JQ1 effectively
      suppresses the proliferation, migration, and invasion of osteosarcoma cells.
      Mechanistically, THZ1 treatment suppresses a large group of super enhancer
      containing MYC target genes including CDK6 and TGFB2. These findings revealed
      that the MYC-driven super enhancer signaling is crucial for the osteosarcoma
      tumorigenesis and targeting the MYC/super enhancer axis represents as a promising
      therapeutic strategy for treatment of osteosarcoma patients.

PMID- 29644116
TI  - Obesity and Pediatric Psoriatic Arthritis.
AB  - Objective: Studies in adults have shown a significant association between obesity
      and psoriatic arthritis, however the association of obesity with pediatric
      psoriatic arthritis is unknown. We aimed to evaluate obesity in pediatric
      psoriatic arthritis. Methods: We conducted a cross-sectional study of children
      with psoriasis and psoriatic arthritis evaluated at a single center between
      6/2010 and 9/2014. Two healthy reference populations were utilized: 1) local
      reference population from the surrounding community and 2) a national reference
      population derived from NHANES. Age and sex-specific z-scores for weight, height,
      and body mass index (BMI) were calculated. Differences in clinical and
      demographic characteristics between groups were assessed. Results: During the
      study period, 48 children with psoriatic arthritis and 231 patients with
      psoriasis were evaluated. Three (6.2%) and 5 (10.4%) of the children with
      psoriatic arthritis were overweight or obese, respectively. In comparison to the
      reference healthy groups and psoriasis patients, the mean BMI z-score of children
      with psoriatic arthritis was not statistically different. However, patients with
      psoriasis were more likely to be obese than the community reference population (p
      value <0.001). Conclusions: Children with psoriasis were more obese than the
      healthy reference population, however there was no statistically significant
      difference in obesity between children with psoriatic arthritis and psoriasis or
      psoriatic arthritis and the reference population. This lack of association may be
      reflective of true differences in pediatric and adult-onset disease and warrants
      further investigation.

PMID- 29644115
TI  - SHP2 regulates skeletal cell fate by modifying SOX9 expression and
      transcriptional activity.
AB  - Chondrocytes and osteoblasts differentiate from a common mesenchymal precursor,
      the osteochondroprogenitor (OCP), and help build the vertebrate skeleton. The
      signaling pathways that control lineage commitment for OCPs are incompletely
      understood. We asked whether the ubiquitously expressed protein-tyrosine
      phosphatase SHP2 (encoded by Ptpn11) affects skeletal lineage commitment by
      conditionally deleting Ptpn11 in mouse limb and head mesenchyme using "Cre-loxP"
      mediated gene excision. SHP2-deficient mice have increased cartilage mass and
      deficient ossification, suggesting that SHP2-deficient OCPs become chondrocytes
      and not osteoblasts. Consistent with these observations, the expression of the
      master chondrogenic transcription factor SOX9 and its target genes Acan, Col2a1,
      and Col10a1 were increased in SHP2-deficient chondrocytes, as revealed by gene
      expression arrays, qRT-PCR, in situ hybridization, and immunostaining.
      Mechanistic studies demonstrate that SHP2 regulates OCP fate determination via
      the phosphorylation and SUMOylation of SOX9, mediated at least in part via the
      PKA signaling pathway. Our data indicate that SHP2 is critical for skeletal cell
      lineage differentiation and could thus be a pharmacologic target for bone and
      cartilage regeneration.

PMID- 29644118
TI  - Increasing Diversity in the Health Professions: Reflections on Student Pipeline
      Programs.
AB  - Despite major advances and technological improvements in public health and
      medicine, health disparities persist by race and ethnicity, income and
      educational attainment, and in some cases are increasing (Jackson & Garcia,
      2014). These health disparities among these populations have even worsened or
      remained about the same since the landmark 1985 Report of the Secretary's Task
      Force on Black & Minority Health released by then Secretary Margaret M. Heckler.
      Ensuring diverse public health and healthcare workforces to provide services to
      diverse populations, in combination with other strategies, can increase access to
      and quality of healthcare for vulnerable populations and decrease healthcare
      disparities. One mechanism for achieving a diverse public health and healthcare
      workforce is to establish, promote, and conduct student training programs in
      public health. The Office of Minority Health and Health Equity, Centers for
      Disease Control and Prevention (CDC), has partnered with institutions, colleges,
      universities, foundations, national organizations and associations to form and
      implement student training programs. This paper highlights a session "Public
      Health Professions Enhancement Programs" that was held during the 2015 symposium
      titled "National Negro Health Week to National Minority Health Month: 100 Years
      of Moving Public Health Forward" in Atlanta, Georgia. Presenters at the symposium
      consisted of interns and fellows who had participated in student programs in the
      Office of Minority Health and Health Equity at the CDC.

PMID- 29644117
TI  - Identifying Links Between Sexual Violence and Youth Violence Perpetration: New
      Opportunities for Sexual Violence Prevention.
AB  - Objective: One promising opportunity for advancing sexual violence (SV) research
      and identifying new avenues for prevention involves examining other forms of
      violence that may share risk factors with SV. Youth violence (YV) is ideal for
      consideration given evidence of overlap in SV and YV risk factors, a large set of
      established YV risk factors across the social ecology, and the number of evidence
      based YV prevention strategies available. The current paper identifies shared and
      unique risk factors for SV and YV and highlights evidence-based YV prevention
      strategies that impact these shared risk factors. Conclusions: Researchers and
      program developers should consider adapting and evaluating evidence-based YV
      prevention strategies to prevent SV. Modifying these programs to address SV's
      unique risk factors may maximize their potential effectiveness. In addition,
      expanding SV research at the outer levels of the social ecology is critical to
      developing community-level prevention strategies. The YV literature suggests
      several potential risk factors at these levels in need of research for SV,
      including school connectedness, social disorganization, and availability of
      alcohol and drugs. Using the YV literature as a starting point for expanding SV
      research leverages prior investments in YV research, may help identify new SV
      prevention strategies at a limited cost, and moves the field more quickly toward
      implementation of cost-effective, multidomain violence prevention strategies in
      communities.

PMID- 29644119
TI  - European Board for Accreditation in Cardiology (EBAC) 2015 CME/CPD Survey
      Summary.
AB  - In the spring of 2015, the European Board for Accreditation in Cardiology (EBAC)
      collaborated with International CME/CPD Consulting to design and administer a
      survey to approximately 1,171 professionals active in the field of European
      CME/CPD, with a focus on cardiology. With a nearly 5% response rate, the results
      herewith are non-representative, but do express current behaviours and attitudes
      of those active in European accredited CME/CPD.

PMID- 29644120
TI  - Assessment of a high-fidelity mobile simulator for intrauterine contraception
      training in ambulatory reproductive health centres.
AB  - OBJECTIVES: Little is known about the utility of simulation-based training in
      office gynaecology. The objective of this cross-sectional study was to evaluate
      the self-reported effectiveness and acceptability of the PelvicSimTM (VirtaMed),
      a high-fidelity mobile simulator, to train clinicians in intrauterine device
      (IUD) insertion. METHODS: Clinicians at ambulatory healthcare centres
      participated in a PelvicSim IUD training programme and completed a self
      administered survey. The survey assessed prior experience with IUD insertion, pre
      and post-training competency and comfort and opinions regarding the
      acceptability of the PelvicSim. RESULTS: The 237 participants were primarily
      female (97.5%) nurse practitioners (71.3%). Most had experience inserting the
      levonorgestrel LNG20 IUD and the copper T380A device, but only 4.1% had ever
      inserted the LNG14 IUD. For all three devices, participants felt more competent
      following training, with the most striking change reported for insertion of the
      LNG14 IUD. The majority of participants reported increased comfort with uterine
      sounding (57.7%), IUD insertion on a live patient (69.8%), and minimizing patient
      pain (72.8%) following training. Of the respondents, 89.6% reported the PelvicSim
      IUD insertion activities as "valuable" or "very valuable." All participants would
      recommend the PelvicSim for IUD training, and nearly all (97.2%) reported that
      the PelvicSim was a better method to teach IUD insertion than the simple plastic
      models supplied by IUD manufacturers. CONCLUSIONS: These findings support the use
      of the PelvicSim for IUD training, though whether it is superior to traditional
      methods and improves patient outcomes requires evaluation.

PMID- 29644121
TI  - Education, training, and professional issues of radiographers in six European
      countries: a comparative review.
AB  - Radiographers constitute an important part of a multidisciplinary radiation-based
      imaging and therapy chain. However, is there a common framework for assuring high
      education, training, and subsequent practice of profession among European
      countries? A study was conducted, based on a questionnaire that consisted of
      three parts, concerning education and training (Part A), national registry (Part
      B), and professional issues (Part C). Analysis of the collected data suggested
      that a common policy is generally followed in the countries investigated;
      however, differences were not negligible. A common framework of educational
      programmes among European countries could form the basis for overall
      standardisation at national and international level.

PMID- 29644122
TI  - Cologne Consensus Conference: providers in accredited CME/CPD 11-12 September
      2015, Cologne, Germany.
AB  - On 11-12 September 2015, the fourth annual Cologne Consensus Conference (CCC) was
      held in Cologne, Germany. The 2-day educational event was organised by the
      European Cardiology Section Foundation (ECSF) and the European Board for
      Accreditation in Cardiology (EBAC), a specialty continuing medical education
      continuing professional development (CME-CPD) accreditation board of the European
      Union of Medical Specialists (UEMS). The conference was again planned in
      cooperation with an impressive group of international organisations and faculty
      members representing leading European and North American institutions. Each year,
      the CCC is organised around a specific topic area. For the conference's fourth
      iteration, the providers in accredited CME/CPD were the focus. The CCC 2015 set
      out to share ideas, discuss concepts, and increase collaborations amongst the
      various groups. This report provides a summary of the presentations and
      discussions from the educational event.

PMID- 29644123
TI  - Report on Proceedings of the Eighth Annual European CME Forum, Manchester, UK,
      November 2015.
AB  - Delegates from Europe, Asia, and North America attended the Eighth European CME
      Forum in Manchester, UK, on 12 and 13 November 2015. A new format that included
      three separate workshop tracks was introduced. The workshops focused on standards
      and accreditation, education and partnerships, funding and practice in CME/CPD.
      Discussion and interactive sessions on accreditation issues, inter-professional
      education, backwards planning, and patient engagement were among the topics
      addressed. Facilitated conversations were conducted with European leaders in the
      medical profession and a representative from a European commercial supporters'
      organisation. Panel discussions on current and future trends and the views of
      local junior doctors representing the learner community were also conducted.

PMID- 29644124
TI  - State of play of CME in Europe in 2015: Proceedings from the Eighth Annual
      European CME Forum.
AB  - European CME Forum is a not-for-profit organisation that brings together all
      stakeholder groups with an interest in European continuing medical education
      (CME) and promote multichannel discussion in an independent and neutral
      environment. This report summarises the discussions that took place at the 8th
      Annual European CME Forum in Manchester on 11-12 November 2015. Held at a time of
      increased scrutiny on the quality and value of the CME, the forum provided a
      space for attendees to share perspectives on trends, challenges, and
      opportunities related to European CME accreditation, funding, and regulation.
      Discussions focused on specific "hot topics" identified through a pre-meeting
      survey and needs assessment conducted among CME stakeholders in Europe and
      beyond. Chief among these were issues related to managing the transparency of
      relationships between industry and healthcare professionals, evolving systems of
      European CME accreditation, and the future of CME funding. The programme
      structure included multiple workshops conducted by leaders in the CME field, and
      plenary sessions that facilitated multidisciplinary interactions with invited
      guests, including the very learners the CME field is designed to serve. Attendee
      feedback was gathered to begin shaping the programme for the 9th Annual European
      CME Forum (#9ECF), which will take place in Amsterdam, The Netherlands, on 9-11
      November 2016.

PMID- 29644125
TI  - Proceedings of second Indian GAME conference, Mumbai, February, 2016.
AB  - The second Indian Global Alliance for Medical Education (GAME) conference on
      continuing medical education-continuing professional development (CME-CPD) was
      held in Mumbai in February 2016. The main aim of the meeting was to create a
      blueprint for further development of CME in India based on best practices from
      around the world. To that end, delegates had been invited from the USA, the UK
      and Australasia, who engaged in productive discussions with the major
      stakeholders of the CME community in India. The latter included clinicians,
      medical communications representatives and delegates from the pharmaceutical
      industry. The mandatory CME system already established in Maharashtra was
      described as an example, which could be exported to other states. The various
      types of accreditation were discussed, including provider and activity
      accreditation along with hybrid systems. Recommendations for future development
      were proposed from workshops comprising clinicians, industry representatives and
      medical communications agencies.

PMID- 29644126
TI  - Collaborative diabetes training in outpatient primary care.
AB  - Two Universities from Oulu, Finland organised integrated and interprofessional
      (IP) type 2 diabetes training periods for undergraduate medical and nursing
      students in collaboration with the University Hospital and Health and Wellbeing
      Centre of Oulu. There is an ongoing health, social services and regional
      government reform in Finland. The services will be organised in a customer
      orientated way and the reform will combine the primary and secondary services.
      The training was tailored to reflect the real life future setting in Finnish
      primary care, and this model fits well with the principles of collaborative
      education. The study aimed at investigating students' attitudes and readiness for
      inter professional learning and their learning experience in combined primary and
      secondary care settings. The second aim was to strengthen students' professional
      skills by working with patients in a patient-centred manner. The "Readiness for
      Interprofessional Learning Scale" was used with added questions about pair
      training. Students' perceptions of their clinical skills were evaluated. The
      students valued the mutual learning experience in outpatient primary care. They
      felt comfortable with working together and complemented each other. Students
      performed well with IP competencies such as patient centredness, communication
      and team functioning. Patients in general were very satisfied with the visit.
      Teamwork and collaboration, professional identity and pair work were highly
      scored in both student groups while roles and responsibilities were evaluated a
      little less positively. Collaboration between different levels of care and health
      policies is important when developing health professionals' education. This IP
      teamwork experience helps both future and current health-care professionals to
      better organise the care of chronic illnesses.

PMID- 29644127
TI  - Cologne Consensus Conference 2016: assessment in accredited CME/CPD, 16 and 17
      September 2016, Cologne, Germany.
AB  - Participants and faculty members from around Europe and North America met in
      Cologne Germany on 16 and 17 September 2016, for the fifth annual Cologne
      Consensus Conference under the auspices of the European Cardiology Section
      Foundation (ECSF) in cooperation with various European and North American
      professional medical associations, accrediting bodies and CME providers. The
      conference was preceded by an afternoon workshop, organised by the European Board
      for Accreditation in Cardiology (EBAC) that allowed participants to observe a
      range of current e-learning modules in CME and to discuss implications for the
      accreditation of micro-e-learning. The conference theme was Assessment and the
      first day's presentations covered Assessment Methods, Needs Assessment,
      Assessment of Interprofessional Teams, and Assessment of Providers. The second
      day's topics were Assessment of Knowledge, Assessment of Practical Skills,
      Evaluation methods and the link between Assessment and Licensure. A diverse range
      of professional expertise among participants from both sides of the Atlantic
      provided stimulating discussion to make the conference a rewarding experience for
      all concerned.

PMID- 29644128
TI  - Report on Proceedings of the Ninth Annual European CME Forum, Amsterdam, the
      Netherlands, November 2016.
AB  - Participants from as far afield as Australia and North America convened in
      Amsterdam, the Netherlands between 9 and 11 November 2016 to attend the Ninth
      European CME Forum (ECF). The meeting combined panel discussions with a range of
      presentations on topics such as high quality learning, current challenges in CME
      and future trends. However, the bulk of the forum was taken up with interactive
      workshops under three different track headings: Development, Educational Design
      and the CME Environment. Attendees also heard from a group of CME pioneers in a
      pre-conference session on the history of CME on both sides of the Atlantic Ocean.

PMID- 29644129
TI  - Oral rehydration therapy training and clinical simulation experience to improve
      students' confidence in preparation for international medical mission trip to
      Nicaragua.
AB  - In order to better prepare the medical, graduate and undergraduate students
      participating in our international medical mission trip to Nicaragua, we prepared
      and presented a discussion on Oral Rehydration Therapy (ORT) prior to the
      international experience. Additionally, a clinical simulation experience was
      incorporated into our pre-departure training to instruct the students on basic
      clinical skills, medical interviewing and teamwork. As a tool to measure the
      students' prior knowledge on the topic of ORT, we designed a questionnaire, which
      was distributed and collected prior to the training and simulation experience.
      Finally, one day after the ORT training and simulation experience, we distributed
      the same questionnaire and collected the results in order to measure the efficacy
      of the training and simulation on the students' perspective of confidence, as
      well as the students' retention of the information and skills taught. Our study
      population consisted of 9 first-year medical students, 1 graduate student, and 16
      pre-medical students, all of whom participated in all aspects of the study. In
      the pre-training survey, only five of the students indicated that they could
      confidently and effectively explain or administer ORT to someone else. After
      collecting the results from the post-training survey, all of the students
      indicated that they could confidently and effectively explain or administer ORT
      to someone else. We concluded that the ORT training and clinical simulation
      experience, wherein students could actively apply the knowledge they gained on
      the administration of ORT to patients, are effective tools to aid in the
      preparation of medical, graduate and undergraduate students by way of increasing
      students' level of confidence in the subject material prior to embarking on
      international medical mission trips.

PMID- 29644130
TI  - Position paper on current aspects of sponsoring in accredited CME.
AB  - This position paper is the result of a collaborative approach of several European
      Specialty Accreditation Boards (ESABs) and, has been stimulated by their current
      experience in accreditation regarding roles and responsibilities assumed by
      sponsors of accredited continuing medical education (CME). The suggestions made
      in this paper aim to preserve the fundamental principle in CME accreditation that
      the physician in charge of the programme has sole responsibility for the
      selection of topics, speakers, content and format, as well as mode of
      presentation, and that sponsors will under no circumstances interfere with this
      principle. This is considered as a responsibility of an individual physician (or
      physicians), which cannot be delegated, even in part, to third parties. This
      responsibility has been extended to include all communication before and after
      the event. The paper also identifies undecided issues, about which ESABs are
      committed to elaborate proposals in the future.

PMID- 29644131
TI  - Roles and Responsibilities in the Provision of Accredited Continuing Medical
      Education/Continuing Professional Development.
AB  - The Cologne Consensus Conference 2015 has focused on "Providers in accredited
      CME[continuing medical education]/CPD [continuing professional development]". As
      an outcome of the CCC 2015, the authors of this paper, who were part of the
      faculty, propose a contemporary definition of the roles and responsibilities of
      stakeholders involved in the different stages of planning, delivery and
      evaluation of CME/CPD.

PMID- 29644132
TI  - European CME needs the European Specialist Societies.

PMID- 29644133
TI  - Preferences and attitudes of physicians in India towards continuing medical
      education.
AB  - Introduction: Physicians in India display an enthusiasm for continuing medical
      education (CME), however a proper system for facilitation and organisation of CME
      activities is yet to evolve in the country. Methods: A questionnaire-based survey
      was conducted among 751 physicians from eight medical specialties across India
      and the data retrieved was analysed at individual physician and collective
      specialty-specific levels. Results: The surveyed physicians considered case
      presentations (73%), live speaker programmes (70%) and round-table meetings/focus
      group meetings (70%) as the most effective CME activities. They preferred a
      duration of <2 h for CME activities such as webcasts (89%) and lectures (86%).
      Most of them considered scientific agenda (78%) and stature of speakers (77%) as
      the most important determinants of the quality of a CME event. Most physicians
      wanted topics such as disease guidelines (88%) and new
      drugs/devices/interventions (86%) for discussion in CME activities. Medical
      associations (87%) were the most desirable organisations for holding the CME
      activities and face-to-face modules appealed to majority of the physicians (64%).
      Conclusions: This study indicates that Indian physicians prefer live,
      interactive, short, specialty-specific educational sessions for CME activities,
      delivered by Indian experts and organised by medical associations at domestic
      destinations.

PMID- 29644135
TI  - Framework for industry engagement and quality principles for industry-provided
      medical education in Europe.
AB  - Lifelong learning through continuing professional development (CPD) and medical
      education is critical for healthcare professionals to stay abreast of knowledge
      and skills and provide an optimal standard of care to patients. In Europe, CPD
      and medical education are fragmented as there are numerous models, providers and
      national regulations and a lack of harmonisation of qualitative criteria. There
      is continued debate on the appropriate role of pharmaceutical companies in the
      context of medical education. Accrediting bodies such as European Accreditation
      Council for Continuing Medical Education do not permit active involvement of the
      pharmaceutical industry due to concerns around conflicts of interest and
      potential for bias. However, many examples of active collaboration between
      pharmaceutical companies and medical societies and scientific experts exist,
      demonstrating high integrity, clear roles and responsibilities, and fair and
      balanced content. Medical education experts from 16 pharmaceutical companies met
      to develop a set of quality principles similar to standards that have been
      established for clinical trials and in alignment with existing principles of
      accrediting bodies. This paper outlines their proposal for a framework to improve
      and harmonise medical education quality standards in Europe, and is also an
      invitation for all stakeholders to join a discussion on this integrative model.

PMID- 29644134
TI  - Identifying the needs for competency-based education in Europe: a needs
      assessment of cardiologists across 52 countries.
AB  - Objective: This international needs assessment was mandated by the European
      Society of Cardiology (ESC) to obtain an in-depth understanding of the current
      gaps and challenges of European cardiology professionals, with the aim to provide
      evidence for the development of needs-driven educational and professional
      development activities. Methods: This ethics-approved needs assessment was
      conducted among cardiologists from all sub-specialties across 56 countries of
      Europe and the Mediterranean basin. A mixed-methods research approach was used,
      combining qualitative in-depth interviews and focus groups with a quantitative
      survey. Results: Seventy-four (74) cardiologists participated in the qualitative
      phase and 866 completed the survey. Respondents represented 52 of the 56 targeted
      countries. Three themes were identified: 1) Challenges in the clinical decision
      making process, 2) Challenges in establishing the patient-physician relationship,
      and 3) Sub-optimal team communication and collaboration. Specific gaps and
      causalities related to each challenge were found. Although most of the gaps were
      common across countries and sub-specialties, some significant differences were
      noted. Conclusion: The findings of this needs assessment indicate gaps and
      challenges in clinical practice across countries and across sub-specialities.
      Taking cardiology as an example, this study identifies clear areas of focus,
      especially around issues of collaboration and communication, for targeted
      competency-based education in Europe.

PMID- 29644136
TI  - Letter To The Editor: The challenges faced by providers of CME in Europe.

PMID- 29644137
TI  - CIS (change impact score) - a novel outcome measurement tool to quantify the
      relevance of medical education interventions on professional performance.
AB  - Outcome measurements play a key role in professional CME (Continuing Medical
      Education). While assessment of delegate satisfaction and knowledge transfer is a
      common standard, it appears desirable to address higher levels of evidence.
      However, measurement of competence and performance is considered complex,
      difficult and expensive. The CIS (Change Impact Score) is a novel instrument to
      predict the relevance of the educational intervention to the professional
      performance of the physician, based on a standardised on-site self-assessment.

PMID- 29644138
TI  - Independence from industry cannot be compromised.

PMID- 29644139
TI  - Industry - from sponsor to provider?

PMID- 29644140
TI  - International needs analysis in orthopaedic trauma for practising surgeons with a
      3-year review of resulting actions.
AB  - Introduction: To ensure best-quality education in orthopaedic trauma, the
      AOTrauma Education Commission conducted a Global Needs Analysis with practising
      surgeons worldwide. Material and methods: During July to November 2012, an email
      invitation to complete an online set of 30 questions in eight languages was sent
      to our members and associates in all countries through AOTrauma's regional
      networks. Non-members were invited to participate through collaboration with
      orthopaedic societies. Results: A total of 3,790 surgeons practising orthopaedic
      trauma (49%), orthopaedic (15%), general trauma (15%) and specialty orthopaedic
      (13%) surgeons responded worldwide. Seventy per cent completed all questions, and
      the top 10 countries accounted for half the responses. The top 3 areas of
      educational need were orthopaedic trauma, joint replacement and preservation, and
      pelvis and acetabulum. Aspects influencing likelihood to attend face-to-face
      courses were: expert faculty, focus on a specific topic, clear objectives, and
      discussion and feedback from experts. Barriers to attending courses were time
      away from practice, cost and lack of availability or access. Conclusion: The
      Global Needs Analysis helped our educational committees to identify short- and
      mid-term priorities over recent years. Adjustments in our planning have helped
      meet the needs of our audience on a global, regional and national level.

PMID- 29644141
TI  - Learnings and challenges to deploy an interprofessional and independent medical
      education programme to a new audience.
AB  - The importance of interprofessional education (IPE) in continuing medical
      education and professional development has long been recognised by health
      organisations and academic societies, benefiting not only patient outcomes and
      interprofessional relationships but also overall health systems and workforce
      shortage. We report on the outcomes of an Australian IPE activity on medication
      overuse headache (MOH) with general practitioners (GPs) and community pharmacists
      as learners. The design of the activity, which followed the predisposing-enabling
      reinforcing instructional framework by Green and Kreuter, aimed to: (1) improve
      knowledge and foster a willingness in GPs and pharmacists to work collaboratively
      to enhance the prevention, diagnosis and management of MOH; and (2) address their
      educational gap by demonstrating the utility of a blended learning IPE strategy
      on MOH. Integrated into the activity was an assessment of its effectiveness and
      impact to instil change in the participants' knowledge of MOH, attitude and
      willingness to treat, and clinical practice behaviours of GPs and pharmacists to
      work together. The learners gained knowledge and confidence in diagnosing and
      managing MOH and in their ability to educate patients. The IPE approach suited
      the activity and was valued by the participating GPs and pharmacists, who seldom
      experience such learning formats. However, for educational providers in
      Australia, developing and deploying an independent medical education (IME)
      programme can be challenging. Providers of IMEs need to be aware of the potential
      pitfalls when competing with pharmaceutical-company-sponsored and delivered
      programmes.

PMID- 29644142
TI  - Report on Proceedings of the Tenth Annual European CME Forum, Dublin, Ireland,
      November 2017.
AB  - The august setting of the Royal College of Physicians of Ireland saw participants
      from 17 different countries assemble for the Tenth European CME Forum between 8th
      and 10th November 2017. The main themes of the meeting were classified under the
      headings Inward (Educational design), Outward (Listening to others) and Onward
      (Collaborations and partnerships) addressed via a combination of presentations,
      interactive workshops, posters, and panel discussions. Topics explored included
      team engagement, the voice of the patient, harmonisation in European
      accreditation, competencies for CME professionals, and publishing in CME.
      Discussion evoked both consensus and contention and provided participants with
      excellent networking opportunities moving forward to the next decade of Forum
      meetings.

PMID- 29644143
TI  - "Certified ... now what?" On the Challenges of Lifelong Learning: Report from an
      AMEE 2017 Symposium.
AB  - The increasing mobility of patients and healthcare professionals across the
      countries of Europe has highlighted the wide variations in both medical training,
      and provision of medical competency and skills. The maintenance of the standards
      defining competency and skills have national and international implications and
      have proved challenging for national regulatory bodies. Thus each nation has
      introduced different types of Continuing Professional Development (CPD),
      recertification and relicensing systems. At the Symposium entitled: " 'Certified
      ... now what?' On the Challenges of Lifelong Learning" in August 2017 at the
      Association for Medical Education in Europe (AMEE) annual conference, we reviewed
      differing European national relicensing systems were reviewed. The review
      highlighted various lifelong learning and competence assessment approaches using
      examples from different medical specialties across several European countries.

PMID- 29644144
TI  - Comparative Effectiveness of a Bioengineered Living Cellular Construct and
      Cryopreserved Cadaveric Skin Allograft for the Treatment of Venous Leg Ulcers in
      a Real-World Setting.
AB  - Objective: A variety of advanced biological therapies are available for the
      treatment of chronic wounds such as venous leg ulcers (VLUs), but real-world
      comparative effectiveness data that can help guide decisions around treatments
      are currently lacking. Approach: This analysis was designed to compare the
      effectiveness of a bioengineered living cellular construct (BLCC) to a
      cryopreserved cadaveric skin allograft (CCSA) for the treatment of VLUs.
      Treatment records were collected from a large wound care-specific electronic
      medical record database on 717 patients (799 VLUs) receiving treatment at 177
      wound care centers. Ulcers >=28 days duration, between >=1 and < 40 cm2 that
      closed <=40% within the 28 days before treatment were included. Results: Patient
      baseline demographics and wound characteristics were comparable between groups.
      The median time to wound closure was 52% faster with BLCC compared with CCSA (15
      weeks vs. 31 weeks). In addition, the proportion of wounds healed were
      significantly higher for BLCC by 12 weeks (42% vs. 24%) and 24 weeks (65% vs.
      41%) (p = 0.0002). Treatment with BLCC increased the probability of healing by
      97% compared with CCSA (hazard ratio = 1.97 [95% confidence interval 1.39-2.79],
      p = 0.0002). Innovation: This is the first real-world comparative effectiveness
      analysis to evaluate BLCC and CCSA for the treatment of VLUs. Conclusion:
      Treatment with a bioengineered cellular technology significantly improved the
      incidence and speed of wound closure compared with a CCSA.

PMID- 29644145
TI  - Publicly Reported Wound Healing Rates: The Fantasy and the Reality.
AB  - Significance: We compare real-world data from the U.S. Wound Registry (USWR) with
      randomized controlled trials and publicly reported wound outcomes and develop
      criteria for honest reporting of wound outcomes, a requirement of the new Quality
      Payment Program (QPP). Recent Advances: Because no method has existed by which
      wounds could be stratified according to their likelihood of healing among real
      world patients, practitioners have reported fantastically high healing rates. The
      USWR has developed several risk-stratified wound healing quality measures for
      diabetic foot ulcers (DFUs) and venous leg ulcers (VLUs) as part of its Qualified
      Clinical Data Registry (QCDR). This allows practitioners to report DFU and VLU
      healing rates in comparison to the likelihood of whether the wound would have
      healed. Critical Issues: Under the new QPP, practitioners must report at least
      one practice-relevant outcome measure, and it must be risk adjusted so that
      clinicians caring for the sickest patients do not appear to have worse outcomes
      than their peers. The Wound Healing Index is a validated risk-stratification
      method that can predict whether a DFU or VLU will heal, leveling the playing
      field for outcome reporting and removing the need to artificially inflate healing
      rates. Wound care practitioners can report the USWR DFU and VLU risk-stratified
      outcome measure to satisfy the quality reporting requirements of the QPP. Future
      Directions: Per the requirements of the QPP, the USWR will begin publicly
      reporting of risk-stratified healing rates once quality measure data have met the
      reporting standards of the Centers for Medicare and Medicaid Services. Some basic
      rules for data censoring are proposed for public reporting of healing rates, and
      others are needed, which should be decided by consensus among the wound care
      community.

PMID- 29644146
TI  - Xanthine Oxidoreductase: A Novel Therapeutic Target for the Treatment of Chronic
      Wounds?
AB  - Significance: Chronic wounds are a major burden to patients and to healthcare
      systems worldwide. These wounds are difficult to heal and treatment is often
      lengthy and expensive. This has led to research efforts focussed on the wound
      environment attempting to understand the underlying pathological mechanisms of
      impaired wound healing. While some of this research has translated to
      advancements in wound therapies and implementation of new treatment options,
      chronic wounds remain a significant challenge to treat. Thus, identification of
      effective, low-cost, advanced wound therapies that enhance healing rates of these
      problematic wounds is still essential. Recent Advances and Critical Issues:
      Xanthine oxidoreductase (XOR), a molybdoflavin enzyme, is emerging as an
      important source of reactive oxygen species (ROS) in various pathologies,
      including diabetes and chronic wounds. XOR has recently been shown to be
      upregulated in chronic wounds, stimulating the overproduction of ROS during
      dysfunctional wound healing. XOR-induced ROS can amplify and potentiate
      inflammation in the wound environment further delaying wound closure. Future
      Directions: The detrimental role of XOR in impaired healing indicates it may be a
      therapeutic target. Targeted inhibition of XOR has been shown to reduce the
      expression and activity of this enzyme in diabetic wound models. In turn, this
      resulted in a significant decrease in ROS levels in the wound environment and
      improved wound healing. Therefore, repurposing existing XOR inhibitors that are
      approved for human use may be able to restore homeostasis at the wound site and
      enable damaged tissue to return to normal healing.

PMID- 29644147
TI  - Food Insecurity, Not Stress is Associated with Three Measures of Obesity in Low
      Income, Mexican-American Women in South Texas.
AB  - Objective: To determine the relationship between obesity, food insecurity and
      perceived stress in very low income Mexican American women. Design: Cross
      sectional baseline data analysis of a randomized clinical trial. Setting: Texas
      Mexico border region of South Texas. Subjects: Very Low Income Mexican American
      Women. Results: The relationship between obesity and food insecurity in a sample
      of very low income Hispanic women living in South Texas depends on the measure of
      obesity and the dimension of food insecurity. The only measure of food insecurity
      associated with all measures of obesity was often not having enough money to
      afford to eat balanced meals. Waist circumference was associated with the most
      dimensions of food insecurity, while BMI had the least associations. Finally,
      perceived stress was not significantly associated with BMI, waist circumference
      or percent body fat when adjusted for other covariates. Conclusions: We have
      found a strong and significant relationship between food insecurity related to
      having enough resources to eat a balanced diet and BMI, waist circumference, and
      percent body fat in low-income Mexican American women. While behavioural change
      is an important strategy for reducing obesity, consideration may need to be made
      as to how food access with high nutritional value, may be in and of itself a
      contributing factor in obesity in low income populations.

PMID- 29644148
TI  - Differential Deposition of Fluorescently Tagged Cholesterol on Commercial Contact
      Lenses Using a Novel In Vitro Eye Model.
AB  - Purpose: We evaluate the differences in lipid uptake and penetration in daily
      disposable (DD) contact lenses (CL) using a conventional "in-vial" method
      compared to a novel in vitro eye model. Methods: The penetration of fluorescently
      labelled 22-(N-(7-Nitrobenz-2-Oxa-1,3-Diazol-4-yl)Amino)-23,24-Bisnor-5-Cholen
      3beta-Ol (NBD)-cholesterol on three silicone hydrogel (SH) and four conventional
      hydrogel (CH) DD CLs were investigated. CLs were incubated for 4 and 12 hours in
      a vial, containing 3.5 mL artificial tear solution (ATS), or were mounted on an
      in vitro eye-blink platform designed to simulate physiologic tear flow (2 mL/24
      hours), tear volume and "simulated" blinking. Subsequently, CLs were analyzed
      using laser scanning confocal microscopy and ImageJ. Results: Penetration depth
      and fluorescence intensities of NBD-cholesterol varied between the incubation
      methods as well as lens materials. Using the traditional vial incubation method,
      NBD-cholesterol uptake occurred equally on both sides of all lens materials.
      However, using our eye-blink model, cholesterol penetration was observed
      primarily on the anterior surface of the CLs. In general, SH lenses showed higher
      intensities of NBD-cholesterol than CH materials. Conclusions: The traditional
      "in-vial" incubation method exposes the CLs to an excessively high amount of ATS,
      which results in an overestimation for cholesterol deposition. Our model, which
      incorporates important ocular factors, such as intermittent air exposure, small
      tear volume, and physiological tear flow between blinks, provides a more natural
      environment for in vitro lens incubation. Translational Relevance: In vitro
      measurements of CLs are a common approach to predict their interactions and
      performance on the eye. Traditional methods, however, are rudimentary. Therefore,
      this study presents a novel in vitro model to evaluate CLs, which consequently
      will enhance elucidations of the interactions between CLs and the eye.

PMID- 29644149
TI  - Cardiovascular Disease Risk in Obstructive Sleep apnea: An Update.

PMID- 29644150
TI  - It's About Time: Examining the Effect of Interviewer-Quoted Survey Completion
      Time Estimates on Survey Efficiency.
AB  - Declining response rates may introduce bias into survey results and increase
      costs. Two national surveys, the National Immunization Survey (NIS) and the NIS
      Teen, were used to study the impact of survey length, as stated by the
      interviewer, and inclusion of a topic of interest to respondents on response
      rates. The two studies included comparisons of the standard survey instruments to
      revised, condensed instruments. The NIS study also included variations of the
      standard survey with sections considered of interest for parental respondents,
      the Parental Concerns Module (PCM), which contained questions about parents'
      thoughts and beliefs about vaccinations. The outcomes of interest were
      differences in the response rates and resulting survey costs in each of the study
      conditions. The shortened instruments resulted in higher response rates compared
      to both the standard instruments and the instruments including the PCM and
      reduced the overall time needed to complete an interview. Based on these results,
      the NIS and NIS-Teen questionnaires were both shortened.

PMID- 29644151
TI  - Trans-cranial Doppler as an Ancillary Study Supporting Irreversible Brain Injury
      in a Post Cardiac Arrest Patient on Extracorporeal Membrane Oxygenation.
AB  - Obtaining neuroimaging in patients on cardiopulmonary support devices such as
      extracorporeal membrane oxygenation (ECMO) can be challenging, given the
      complexities in monitoring, instrumentation, and associated hemodynamic lability.
      Transcranial Doppler (TCD) is used as an ancillary test for the assessment of
      cerebral circulatory arrest, but its use in non-pulsatile blood flow in
      venoarterial (VA) ECMO is not well described. We report the use of TCD in a
      patient on VA ECMO post-cardiac arrest for evaluation of death by neurological
      criteria. A 72-year-old female was admitted for elective trans-catheter aortic
      valve replacement. Her postoperative course was complicated by hemo-pericardium
      evolving into pulseless electrical activity causing cardiac arrest. She was
      resuscitated with return of spontaneous circulation and initiated on VA ECMO and
      intra-aortic balloon pump for cardiogenic shock. Over the next few days, serial
      evaluations persistently showed a poor neurological examination. She was too
      unstable to transport for neuroimaging. Evaluation for death by neurological
      criteria was performed with a clinical examination, apnea testing, and TCD as an
      ancillary study. TCD showed systolic spikes supporting an impression of cerebral
      circulatory arrest consistent with an irreversible brain injury.

PMID- 29644152
TI  - The Fight Against Cancer: Nitrobenzaldehyde as the Potential Warrior.
AB  - New milestones have been reached in oncology with the advent of a noninvasive,
      photodynamic therapy which aims to eradicate cancer cells rapidly. A chemical
      compound, Nitrobenzaldehyde, injected into the tumor, activates by ultraviolet
      (UV) light and disrupts the cancer cells' internal and external dynamics. This
      technique could be of enormous therapeutic value in destroying numerous cancer
      lines including breast, prostate, pancreatic cancers, etc., without causing
      unwanted systemic side effects.

PMID- 29644153
TI  - Acute Fatty Liver of Pregnancy: A Thorough Examination of a Harmful Obstetrical
      Syndrome and Its Counterparts.
AB  - Diagnosed in one of every 20,000 deliveries, acute fatty liver of pregnancy
      (AFLP) was considered to be a deadly disease for many years. However,
      advancements in the clinical and surgical management of pregnant mothers have
      lead to a drastic decrease in maternal morbidity and mortality. The corresponding
      case recounts a 23-year-old gravida 2 para 1 (G2P1) at 38 weeks gestational age
      (GA) with no relevant past medical or family medical history that presented to
      the emergency department (ED) with a five-day history of nausea, protracted
      vomiting, hypertension, and new-onset headache. Being late in the third
      trimester, preeclampsia was the top differential diagnosis while awaiting
      additional laboratory work-up. The work-up later revealed elevated liver function
      tests and bilirubin plus an abnormal coagulation profile with low fibrinogen. The
      differential was then shifted to AFLP versus hemolysis-elevated liver enzymes-low
      platelets (HELLP) syndrome. The patient was promptly transferred to the labor and
      delivery unit for close monitoring and delivery planning. Upon cervical
      examination, the patient was not dilated and was therefore determined to be
      remote from delivery. A cesarean section was performed and the mother was
      transferred to the intensive care unit (ICU) post-operatively to optimize
      management of her coagulopathy. Her abnormal laboratory studies normalized by
      post-operative day four and she was discharged home with her newborn.

PMID- 29644154
TI  - What Do Patients Think About Their Radiation Oncologists? An Assessment of Online
      Patient Reviews on Healthgrades.
AB  - Introduction An increasing number of patients search for their physicians online.
      Many hospital systems utilize Press-Ganey studies as internal tools to analyze
      patient satisfaction, but independent third-party websites have a large presence
      online. Patients' trust in these third-party sites may occur despite a low number
      of reviews and a lack of validity of patients' entries. Healthgrades.com has been
      shown as the most popular site to appear on Google searches for radiation
      oncologists (ROs) in the United States (US). The aim of this study was to analyze
      patient satisfaction scores and the factors that influence those scores for
      American ROs on Healthgrades. Methods The physician ratings website Healthgrades
      was manually queried to obtain reviews from all Medicare-participating ROs with
      reviews (n=2,679). Patient Review Satisfaction Scores (PRSS) were recorded in
      response to a variety of questions. All information in the survey was scored from
      1 (poor) to 5 (excellent) for the following characteristics: likelihood to
      recommend (LTR), office environment, ease of scheduling, trust in the physician's
      decision, staff friendliness, ability of the physician to listen and answer
      questions, ability of the physician to explain the condition, and whether the
      physician spent sufficient time with the patients. Associations amongst these
      factors were considered by computing Spearman correlation coefficients and
      utilizing Mann-Whitney and Kruskal-Wallis tests. Results The ROs' mean LTR score
      was 4.51+/-0.9 (median 5.0, 66% received the highest possible score of 5; 95%
      received a score>2). Patient reviews per RO ranged from 1 to 242 (4.50+/-0.9,
      median 2.0). LTR scores correlated very strongly with physician-related factors,
      ranging from r=0.85 (with appropriate time spent with patients) to r=0.89 (with
      level of trust in physician). LTR scores were not statistically significantly
      associated with gender, wait time, ROs' years since graduation, academic status,
      or geographic region. Conclusion Satisfaction scores for ROs on a leading
      physician ratings website are very strong, and most patients leaving reviews are
      likely to recommend their own ROs to their friends and family. Understanding
      online ratings and identifying factors associated with positive ratings are
      important for both patients and ROs due to the recent growth in physician-rating
      third-party sites. ROs should have increased awareness regarding sites like
      Healthgrades and their online reputation.

PMID- 29644155
TI  - Stereotactic Body Radiation Therapy for Pulmonary Oligometastases Arising from
      Non-lung Primaries in Patients Without Extrapulmonary Disease.
AB  - Purpose Stereotactic body radiation therapy (SBRT) is increasingly used in the
      management of patients with oligometastatic cancers and is under prospective
      evaluation by the Radiation Therapy Oncology Group (RTOG). Here we report
      outcomes from a high-volume institution of patients treated with SBRT for
      pulmonary oligometastases. Materials and methods We conducted a retrospective
      review of 105 patients who had one to five pulmonary oligometastases (185
      lesions) without extrapulmonary disease treated with SBRT from 2002-2014. Target
      failure-free survival (TFFS), progression-free survival (PFS), and overall
      survival (OS) were calculated. Univariate and multivariate Cox regression
      analyses were performed on factors predictive of outcomes. Results The median age
      at first SBRT was 68 years and the median follow-up was 29.5 months. The median
      time from initial diagnosis of primary to SBRT was 42.7 months; 14.3% had
      synchronous oligometastases and 76.7% had one to two pulmonary lesions at first
      SBRT. The distribution of primaries was as follows: 36.2% colorectal, 16.2%
      head/neck, 9.5% genitourinary, 9.5% sarcoma, 7.6% gynecologic, 6.7% other, 5.7%
      breast, 5% melanoma, and 4% esophageal. The median lesion size was 1.6 cm and the
      most common regimen was 60 Gy in three fractions (range: 12-60 Gy in one to five
      fractions). TFFS was 94.4% and 90.8% at two and three years, respectively. Two
      and three year OS were 87.9% and 60.2%, respectively. Median PFS and OS were 16.2
      and 45.3 months, respectively. In multivariate analysis, age at primary cancer
      diagnosis and biologically effective dose with an alpha-beta ratio of 10 (BED10)
      were identified as factors significantly affecting OS (p<0.05). Conclusions
      Comprehensive treatment of pulmonary oligometastases with SBRT in the absence of
      extrapulmonary disease results in excellent target control and modest survival
      outcomes.

PMID- 29644156
TI  - Group A Streptococcal Pyomyositis in a Previously Healthy Six-year-old Girl.
AB  - A six-year-old previously healthy girl was seen in an outpatient pediatric clinic
      in the western United States for thigh pain. The pain was accompanied by an
      initial fever and was most severe after periods of prolonged rest. During the
      evaluation, her exam rapidly progressed with severe episodic pain and tenderness
      of the right anteromedial thigh. Magnetic resonance imaging (MRI) demonstrated
      signal enhancement at the insertion of the right obturator externus muscle. Blood
      culture was positive for Group A Streptococcus. She was diagnosed with
      pyomyositis of the right obturator externus and was successfully treated with
      antimicrobials. This case demonstrates a rare case of streptococcal pyomyosits,
      in a temperate climate, without known predisposing factor or injury. We review
      the epidemiology of streptococcal pyomyositis in temperate climates and discuss
      the presentation of pyomyositis in children.

PMID- 29644157
TI  - Persistent Bradycardia with the Long-term Use of Phenytoin and Oxycodone: First
      Case Report.
AB  - Phenytoin is a medication that is used primarily in the treatment of epilepsy as
      well as generalized tonic-clonic seizures and status epilepticus. Phenytoin is
      also considered a class IB antiarrhythmic medication by shortening the duration
      of the action potential and increasing myocardial conduction. The neurologic
      adverse effects of phenytoin are well-documented and include altered mental
      status, ataxia, and nystagmus. Some adverse cardiac manifestations have also been
      reported, including arrhythmias, hypotension, and respiratory arrest. Oxycodone
      is an opioid that exerts its effects by binding to Mu opioid receptors located in
      the central nervous system. This selective binding results in the opening of
      potassium (k+) channels and the closing of calcium channels, decreasing synaptic
      transmission. Oxycodone, unlike phenytoin, has not been observed to elicit
      cardiotoxicity independent of other medications. However, in combination with
      other medications, bradycardia and hypotension have been observed. We report the
      case of a 62-year-old male who developed persistent bradycardia following
      treatment with phenytoin and oxycodone for seizure disorder and pain,
      respectively. To our knowledge, this is the first case report where bradycardia
      was induced by a combination of these medications.

PMID- 29644158
TI  - Bilateral Simultaneous Temporal Relapses of Medulloblastoma.
AB  - Supratentorial relapses are a common component of medulloblastoma after failure
      of treatment. Craniospinal irradiation (CSI) to cerebrospinal fluid-bearing areas
      is an essential part of the management of these tumors both in adults and
      children. Failure of treatment in specific anatomical regions can be attributable
      to technical inaccuracies in CSI technique leading to radiation underdosing in
      such areas. We present two cases of patients with bilateral simultaneous
      metastasis of a primary medulloblastoma treated, in both cases, four years before
      the recurrence. In both patients the tumors were mirror images, at the right and
      left temporal pole. Radiotherapeutic plans were analyzed in both cases, and a
      possible mechanism determining the pattern of relapse is discussed. We consider,
      in agreement with the literature, that a prone position during treatment,
      shielding blocks at the cribiform/subfrontal region, and anatomic inadequacies in
      the CSI fields could have contributed to the presented pattern of relapse.

PMID- 29644159
TI  - Cranial Nerve Foramina Part I: A Review of the Anatomy and Pathology of Cranial
      Nerve Foramina of the Anterior and Middle Fossa.
AB  - Cranial nerve foramina are integral exits from the confines of the skull. Despite
      their significance in cranial nerve pathologies, there has been no comprehensive
      anatomical review of these structures. Owing to the extensive nature of this
      topic, Part I of our review, presented here, focuses on the foramina of the
      anterior and middle cranial fossae, discussing each foramen's shape, orientation,
      size, surrounding structures, and structures that traverse them. Furthermore, by
      comparing the size of each foramen against the cross-sectional areas of its
      contents, we estimate the amount of free space in each. We also review lesions
      that can obstruct the foramina and discuss their clinical consequences.

PMID- 29644161
TI  - Sleep Deprivation Therapy Enhanced Via Repetitive Transcranial Magnetic
      Stimulation in Major Depression.
AB  - Transcranial magnetic stimulation (rTMS) and sleep deprivation (SD) are two of
      the latest advances made in the field of psychiatric research. Though yet in
      development, they present unique opportunities to achieve significant clinical
      outcomes particularly in major depression disorder (MDD). A limited set of
      studies have been done in the combined use of rTMS-SD in treating MDD. While
      promising, these studies have been hampered by the limited knowledge of rTMS and
      SD themselves due to their relatively recent use as viable therapeutic options.
      This review is aimed at an analysis of the limitations observed in the studies
      conducted to date involving rTMS and SD. In addition, it explores the potential
      new avenues for future research in the deployment of rTMS-SD as a viable
      treatment option.

PMID- 29644160
TI  - Wilson's Disease: Expect the Unexpected.
AB  - A 64-year-old woman, presented with abdominal distention, jaundice and resting
      tremor, was found to have liver injury and abnormal liver enzymes. A computed
      tomography (CT) scan of the abdomen and pelvis showed abdominopelvic ascites and
      signs of liver cirrhosis. An extensive liver disease workup was performed and
      came back negative; therefore, a liver biopsy was obtained and showed evidence of
      cirrhosis with elevated liver copper consistent with Wilson's disease (WD). We
      report a unique case of late-onset WD in which the ceruloplasmin level and 24-h
      urinary copper excretion were all normal.

PMID- 29644162
TI  - Clinical Study on Middle Ear Diseases in Children with Orofacial Clefts.
AB  - Introduction Orofacial clefts are associated with middle ear diseases, but the
      magnitude of this problem is not generally well appreciated. The aim of this
      study was to describe the middle ear findings and audiological profile in
      children with orofacial clefts. Materials and methods Children with orofacial
      clefts attending plastic surgery and otorhinolaryngology departments of a
      tertiary hospital over one-year duration were included in this study. Ninety-six
      children with orofacial clefts were identified. They were categorized age-wise as
      zero to five years, more than five years to 10 years, and more than 10 years to
      15 years. They underwent a detailed ear, nose, and throat examination followed by
      audiological tests, including brainstem evoked response audiogram (BERA), pure
      tone audiogram (PTA), and tympanometry. Results Among 96 children with orofacial
      clefts, only 24 children (25%) had symptomatic ear problems, whereas on ear
      examination, 56 children (58.3%) had abnormal ear findings. Middle ear effusion
      (MEE) was the most common ear condition, and it was seen in 94 ears (48.9%).
      Cholesteatoma was noted in six children (3.1%). Out of 73 children in the zero to
      five age group, 58 children (79.5%) did not have any history of ear problem but
      55.5% (81 ears) had features of MEE such as a dull tympanic membrane (TM). In the
      age group of more than five years to 10 years, only four children (28.5%) were
      symptomatic. Five children (55.5%) out of nine in the age group of more than 10
      years had a symptomatic ear problem of which four children (44.4%) had chronic
      otitis media squamosal disease. The earlier age groups showed a trend of ear
      disease being asymptomatic compared to older children. Normal hearing was present
      in only 40 children (41.7%) and various degrees of hearing loss were seen in 56
      children (58.3%). The mean air conduction threshold in the age group zero to five
      years, more than five years to 10 years, and more than 10 years were 33+/-8.3
      decibels (dB), 25+/-6.2 dB, and 31.5+/-14 dB, respectively. Out of 144 ears (72
      children) in the asymptomatic group, 67 ears (46.5%) had normal hearing. Seventy
      seven ears (53.5%) had some degree of hearing loss. Mean air conduction hearing
      loss in the asymptomatic group was 29.8+/-7.3 dB. Conclusion This study
      highlights the higher incidence of middle ear diseases compared to the presenting
      symptoms in children with orofacial clefts. This stresses on the need for a
      detailed otological evaluation to identify any middle ear pathology so that
      timely intervention can be taken.

PMID- 29644164
TI  - The extra-tunical grafting procedure for Peyronie's disease hourglass and indent
      deformities.
AB  - Background: To describe a novel, tunica-sparing surgical technique-extra-tunical
      grafting (ETG)-for the treatment of penile indent and hourglass (HG) deformities
      and to describe patient-reported outcomes after the ETG procedure. Methods: An
      IRB-approved, retrospective chart review of ETG patients was performed to collect
      data including pre-operative deformity, operation performed, and post-operative
      patient-reported perception of deformity, erectile function, penile sensation,
      and overall satisfaction with the ETG operation. The indications for surgery were
      difficulty with sexual intercourse due to deformity and/or poor cosmesis of the
      penis. Pre-operatively all patients had erections adequate for intercourse with
      or without medications. The ETG procedure is performed through a ventral
      longitudinal penile skin incision. The dissection is continued to the level
      between Dartos and Bucks fascia, circumferentially for HG deformity and focally
      for indent deformity. The neurovascular bundle (NVB) is left undisturbed. A
      cadaveric fascia graft is applied, singly or in multiple layers, to fill the
      exposed tunical depressions. Our preferred graft material is Tutoplast Suspend(r)
      (Coloplast, Minneapolis, MN, USA). The graft is sutured into position with
      multiple interrupted, long-lasting absorbable sutures to achieve the desired
      penile shaft contour. The urethra is excluded from the graft. Results: From
      October 2013 to June 2017, 36 patients had the ETG procedure for HG and/or indent
      with or without penile curvature. Results with a minimum of 6 months of follow-up
      could be extracted for 18 of the patients. One was excluded as he required
      concurrent excision of a large calcified tunical plaque, which necessitated
      incision into the tunica albuginea (TA). Follow-up was between 6 and 44 months
      (average 21 months). All patients reported satisfactory resolution of the HG or
      indent. No patient reported worsened erectile function. Two patients (11.8%)
      reported slight penile hypoesthesia, with one of these having had multiple
      previous penile degloving surgeries for trauma. Ten of the patients reported
      being "very satisfied" and six reported being "satisfied" with the procedure. One
      was neutral. All reported that they would recommend the ETG procedure to a
      friend, and all would repeat the same surgery again. Conclusions: The ETG
      procedure is a straightforward approach to HG and indent deformities to correct
      the penile deformity and to provide structural support to prevent penile buckling
      during intercourse. The procedure does not violate the TA and does not require
      dissection of the NVB. Thus, ETG carries a very low risk of de novo impotence or
      hypoesthesia as highlighted by this patient series. With such low risk and high
      patient-reported satisfaction rates, the ETG procedure is a valuable surgical
      technique for the treatment of complex penile deformities.

PMID- 29644163
TI  - Artificial Antigen Presenting Cells: An Off the Shelf Approach for Generation of
      Desirable T-Cell Populations for Broad Application of Adoptive Immunotherapy.
AB  - Adoptive transfer of antigen specific T-cells can lead to eradication of cancer
      and viral infections. The broad application of this approach has further been
      hampered by the limited availability of adequate numbers of T-cells for treatment
      in a timely manner. This has led to efforts for the development of efficient
      methods to generate large numbers of T-cells with specificity for tumor or viral
      antigens that can be harnessed for use in cancer therapy. Recent studies have
      demonstrated that during encounter with tumor antigen, the signals delivered to T
      cells by professional antigen-presenting cells can affect T-cell programming and
      their subsequent therapeutic efficacy. This has stimulated efforts to develop
      artificial antigen-presenting cells that allow optimal control over the signals
      provided to T-cells. In this review, we will discuss the cellular artificial
      antigen-presenting cell systems and their use in T-cell adoptive immunotherapy
      for cancer and infections.

PMID- 29644165
TI  - Treatment of stress urinary incontinence with low-intensity extracorporeal shock
      wave therapy in a vaginal balloon dilation induced rat model.
AB  - Background: To investigate the outcomes and mechanisms of low-intensity
      extracorporeal shock wave therapy (Li-ESWT) on stress urinary incontinence (SUI)
      in a vaginal balloon dilation (VBD) rat model. Methods: Thirty Sprague-Dawley
      rats were randomly grouped into normal controls, VBD only, and VBD with Li-ESWT.
      Li-ESWT was administered twice per week for 3 weeks. Afterward, all 30 rats were
      assessed with functional and histological studies. To explore the acute effect of
      Li-ESWT, another 25 rats, given intraperitoneal 5-ethynyl-2-deoxyuridine (EdU) at
      birth, were treated with Li-ESWT followed by assessment of vascular endothelial
      growth factor (VEGF) expression and endogenous progenitor cells distribution at
      24 hours or 1 week after the last Li-ESWT therapy. Additionally, rat myoblast L6
      cells were used for myotube formation assay in vitro. Results: Functional
      analysis with leak-point pressure (LPP) testing showed that rats treated with Li
      ESWT following VBD had significantly higher LPP relative to those receiving VBD
      only (44.8+/-3.2 versus 27.0+/-2.9 cmH2O, P<0.01). Histological examinations
      showed increased urethral sphincter regeneration in Li-ESWT group. The rats
      treated with Li-ESWT also had increased vascularity, which was confirmed by
      immunohistochemistry of rat endothelial cell antigen, while reverse-transcriptase
      polymerase chain reaction (RT-PCR) showed VEGF expression was significantly
      enhanced. Additionally, there were significantly increased EdU+ cells in Li-ESWT
      treated rats at 24 hours. In vitro, Li-ESWT promoted myotube formation from L6
      cells. Conclusions: Li-ESWT ameliorated SUI by promoting angiogenesis, progenitor
      cell recruitment, and urethral sphincter regeneration in a rat model induced by
      VBD. Li-ESWT represents a potential novel non-invasive therapy for SUI.

PMID- 29644166
TI  - Electroejaculation combined with assisted reproductive technology in psychogenic
      anejaculation patients refractory to penile vibratory stimulation.
AB  - Background: Psychogenic anejaculation (PAE) is a rare disease in clinic seriously
      affecting quality of life, especially fertility of patients. However, there is
      not an effective treatment for these patients. The aim of the study was to
      evaluate the results of treatment with electroejaculation (EEJ), intrauterine
      insemination (IUI), and intracytoplasmic sperm injection (ICSI) in patients with
      PAE who were refractory to penile vibratory stimulation (PVS). Methods: Twenty
      PVS-refractory patients with PAE were included in the retrospective study. Semen
      was retrieved through EEJ procedures. According to the semen quality and patient
      preference, IUI or ICSI was selected. Results: A total of 23 procedures of EEJ
      were performed in 20 patients. Sperm was successfully retrieved in all of the
      cases. Yielded semen was used in a total of 16 ICSI procedures in 6 couples. The
      fertilization rate was 54.0%. The ICSI cycles resulted in three pregnancies; of
      these one resulted in a live birth. Fourteen couples were treated with 26 IUI
      cycles, which resulted in live births in five pregnancies. Conclusions: EEJ
      offers an encouraging pregnancy opportunity for men with PAE who were refractory
      to PVS. The combined use of EEJ and assisted reproductive techniques is excellent
      management for PAE infertility. In our study, EEJ resulted in pregnancies and the
      birth of six healthy children.

PMID- 29644167
TI  - Chronic scrotal pain may lead to reduced sexual function and interest, while
      sexual activity may worsen chronic scrotal pain: "double jeopardy".
AB  - Background: While it is recognized that chronic pain may adversely impact sexual
      function and activity in men and we also recognize that sexual activity may
      worsen the pain for men with chronic scrotal pain (CSP), the effect on sexual
      functioning and conversely the impact of sex on CSP has not previously been
      documented. Methods: Retrospective analysis of a prospectively collected
      database. Results: From Feb 2014 to Sep 2015, a total of 128 men presenting for
      assessment of CSP completed all or parts of a standardized questionnaire. Overall
      60% (69/116) of the men felt that the CSP had kept them either a "lot" or "some"
      of the time from sexual activity and 64% (27/43) had evidence of decreased
      erectile performance. Those with more severe pain (analog pain scores 7-10/10)
      had more significant sexual dysfunction than those with less severe pain, with
      54% (45/83) vs. 0% (0/33, P<0.01: Fisher's exact test) noting that the pain kept
      them from sexual activity "a lot" and 70% (23/33) vs. 40% (4/10, P<0.01) noting
      sexual dysfunction. Diminished libido was also common in the men [43% (55/128)]
      as were the symptoms of testosterone deficiency [76% (97/128)]. Conversely,
      sexual activity often exacerbated the pain, with 37% (47/128) finding that
      ejaculation aggravated their pain and another 38% (48/128) patients found sexual
      activity aggravated their pain. Conclusions: Men with severe CSP have
      significantly reduced sexual function and interest compared to men with moderate
      or minor levels of pain. The majority of men with CSP who were sexually active
      were faced with worsening pain with sex and ejaculation. Clinicians should be
      aware of the twin risks of sexual dysfunction occurring in men with CSP and
      sexual activity worsening the severity of the CSP.

PMID- 29644169
TI  - Testosterone replacement therapy for physician assistants and nurse
      practitioners.
AB  - Physician assistants (PA) and nurse practitioners have been moving toward
      specialty practices, like urology. With increased training and education, they
      manage more complex conditions independently. Whether they are the primary
      provider or the follow up to a specialist, physician extenders can play a vital
      role in managing patients undergoing testosterone therapy. Physician extenders
      should be able to understand the indications, risks and associated adverse
      effects of administering testosterone in order to proficiently take care of
      patients with low testosterone. The goal of this review is to recognize the role
      and the limits to which physician extenders should manage hypogonadism, and when
      physician collaboration or referral is necessary.

PMID- 29644170
TI  - Factors affecting urinary incontinence during robotic radical prostatectomy.

PMID- 29644171
TI  - A novel bladder cancer urinary biomarker: can it go where no marker has gone
      before?

PMID- 29644173
TI  - Identification of hypoxic gene-signature as a prognostic and predictive biomarker
      to determine effective therapy in high risk bladder cancer patients.

PMID- 29644172
TI  - Detection of circulating tumor DNA for advanced bladder cancer: where are we
      going?

PMID- 29644174
TI  - Expansion of clinical application of laparoscopic single-site surgery through
      natural orifice transluminal endoscopic surgery.

PMID- 29644175
TI  - Urinary biomarker for the detection of recurrence following non-muscle invasive
      bladder cancer: are we there yet?

PMID- 29644176
TI  - Robot-assisted laparoscopic implantation of brachytherapy catheters in bladder
      cancer recent interests and prospective.

PMID- 29644168
TI  - Pelvic fracture urethral injury in males-mechanisms of injury, management options
      and outcomes.
AB  - Pelvic fracture urethral injury (PFUI) management in male adults and children is
      controversial. The jury is still out on the best way to manage these injuries in
      the short and long-term to minimise complications and optimise outcomes. There is
      also little in the urological literature about pelvic fractures themselves, their
      causes, grading systems, associated injuries and the mechanism of PFUI. A review
      of pelvic fracture and male PFUI literature since 1757 was performed to determine
      pelvic fracture classification, associated injuries and, PFUI classification and
      management. The outcomes of; suprapubic catheter (SPC) insertion alone, primary
      open surgical repair (POSR), delayed primary open surgical repair (DPOSR),
      primary open realignment (POR), primary endoscopic realignment (PER), delayed
      endoscopic treatment (DET) and delayed urethroplasty (DU) in male adults and
      children in all major series have been reviewed and collated for rates of
      restricture (RS), erectile dysfunction (ED) and urinary incontinence (UI). For
      SPC, POSR, DPOSR, POR, PER, DET and DU; (I) mean RS rate was 97.9%, 53.9%, 18%,
      58.3%, 62.0%, 80.2%, 14.4%; (II) mean ED rate was 25.6%, 22.5%, 71%, 37.2%,
      23.6%, 31.9%, 12.7%; (III) mean UI rate was 6.7%, 13.6%, 0%, 14.5%, 4.1%, 4.1%,
      6.8%; (IV) mean FU in months was 46.3, 29.4, 12, 61, 31.4, 31.8, 54.9. For males
      with PFUI restricture and new onset ED is lowest following DU whilst UI is lowest
      following DPOSR. On balance DU offers the best overall outcomes and should be the
      treatment of choice for PFUI.

PMID- 29644177
TI  - Editorial on "Erectile function and oncologic outcomes following open retropubic
      and robot-assisted radical prostatectomy: results from the LAParoscopic
      Prostatectomy Robot Open Trial".

PMID- 29644178
TI  - Robotic-assisted vs. open radical prostatectomy: an update to the never-ending
      debate.

PMID- 29644179
TI  - Who benefits most from early salvage radiation therapy after prostatectomy?

PMID- 29644180
TI  - Balancing the benefits and harms of radiotherapy post-radical prostatectomy.

PMID- 29644181
TI  - Radium-223 for metastatic castration-resistant prostate cancer: results and
      remaining open issues after the ALSYMPCA trial.

PMID- 29644182
TI  - Editorial on the value of an immediate intravesical instillation of mitomycin C
      in patients with non-muscle-invasive bladder cancer.

PMID- 29644183
TI  - A single immediate instillation of chemotherapy for non-muscle invasive bladder
      cancer: in all patients?

PMID- 29644185
TI  - Dr. Stephen J. Freedland: treating prostate cancer-a healthy lifestyle is what
      matters!

PMID- 29644186
TI  - Dr. Run Wang: penile implant as the first line treatment for severe erectile
      dysfunction.

PMID- 29644184
TI  - Anastomotic leaks and catheter time after salvage robot-assisted radical
      prostatectomy.

PMID- 29644187
TI  - Prof. Steven Patierno: perseverance, creativity and collaboration are the keys to
      successful research.

PMID- 29644188
TI  - Dr. Philippe E. Spiess: right treatments offer patients best chance of cure.

PMID- 29644189
TI  - Dr. Takeshi Arimura: The present and future of proton therapy in Japan.

PMID- 29644190
TI  - Dr. John W. Davis: don't be afraid to start over and learn new things.

PMID- 29644191
TI  - Current Situation of Leprosy in India and its Future Implications.
AB  - The global leprosy situation has changed significantly over the last four decades
      after the introduction of multidrug therapy (MDT) in 1982 with a reduction in
      prevalence from over 5 million cases in the mid-1980s to less than 200,000 at the
      end of 2016. The programme in India also saw a reduction from a prevalence rate
      of 57.8/10,000 in 1983 to less than 1/10,000 by the end of 2005 when India
      declared to have reached the World Health Organization (WHO) target of
      elimination as a public health problem. Post 2005, major changes in the programme
      were made by the National leprosy eradication programme (NLEP) and the global
      leprosy programme, which may have affected the new case detection (NCD),
      disability, and child leprosy trends, which continue to show no appreciable
      regression. This article reviews the current global and Indian leprosy scenario
      to bring out its achievements and successes, including the impact of Leprosy Case
      Detection Campaigns (LCDC) on leprosy numbers. The basis and expected benefits of
      recent introduction of chemo and immune-prophylaxis in the programme are also
      discussed. It also discusses the shortcomings, the areas of concern, and the need
      for an inclusive strategy in the Indian leprosy programme that includes an
      intersectoral collaboration within the country for reaching the desired goal of
      leprosy eradication.

PMID- 29644192
TI  - Is Antifungal Resistance a Cause for Treatment Failure in Dermatophytosis: A
      Study Focused on Tinea Corporis and Cruris from a Tertiary Centre?
AB  - Background: Dermatophytoses are one of the most common skin diseases that have
      been largely simple to treat. However, in recent years, these infections have
      become recalcitrant to treatment which can possibly be due to antifungal
      resistance. Aim: To analyze the resistance pattern of patients with recalcitrant
      dermatophytoses. Materials and Methods: A cross-sectional evaluation was
      undertaken of 40 consecutive patients with recalcitrant tinea
      corporis/cruris/both who had taken systemic antifungal treatment and did not
      respond completely to therapy or had recurrent lesion within 1 month of stopping
      the therapy. Terbinafine, fluconazole, itraconazole, ketoconazole, amphotericin
      B, and voriconazole were the antifungals tested using broth microdilution assay
      for antifungal susceptibility testing of dermatophytes, and MIC50, 90 values were
      recorded. Results: KOH mount was positive in 18 (45%) patients, culture was
      positive in 28 (70%) patients. Trichophyton mentagrophytes (35%) and T. rubrum
      (27.5%) were the predominant isolates. Overall, activity of terbinafine and
      itraconazole were significantly higher than the other drugs tested. For
      terbinafine, both T. mentagrophytes and T. rubrum were inhibited at MIC90 of
      0.125 MUg/ml. Itraconazole-inhibited T. mentagrophytes and T. rubrum at MIC90 of
      0.0625 and 0.25 MUg/ml, respectively. All isolates had reduced susceptibility to
      fluconazole. Conclusion: While MIC seen were higher than western data, in-vitro
      resistance (>1 MUg/ml) to antifungals was not seen and probably may not be a
      cause of treatment failure. Possibly, treatment failure lies in the intricate
      host fungal interaction and virulence of species which help it to evade host
      immune response.

PMID- 29644193
TI  - Nonvenereal Penile Dermatoses: A Retrospective Study.
AB  - Context: A variety of nonvenereal diseases can affect the penis and diminish
      quality of life. Many present similar clinical features and a cutaneous biopsy
      may be necessary to clarify the diagnosis. Aims: To characterize nonvenereal
      penile dermatoses with histological confirmation in a southwestern Europe
      hospital during a 9-year period. Materials and Methods: A retrospective study was
      conducted. We reviewed all penile biopsies performed between January 1, 2007 and
      December 31, 2015 and studied the causes of the nonvenereal penile dermatoses.
      Results: The sample included a total of 108 patients, aged 62.9 (+/-17.8) years,
      between 16 years and 96 years of age. Eighteen dermatoses were identified.
      Inflammatory diseases were present in 65. 7% of patients (71/108) and neoplastic
      dermatoses in 34. 3% (37/108). Concerning inflammatory dermatoses, the most
      frequent were Zoon balanitis (27.8%, 30/108), followed by lichen sclerosus
      (15.7%, 17/108), psoriasis (11.1%, 12/108), and lichen planus (4.6%, 5/108). In
      patients with psoriasis, 10 had lesions only in the penis, similarly to all
      patients with lichen planus. The most frequent malignant tumor was squamous cell
      carcinoma (SCC) (15.7%, 17/108). The most common in-situ tumor was erythroplasia
      of Queyrat (8.3%, 9/108). A case of basal cell carcinoma (BCC) was found. Kaposi
      sarcoma and mycosis fungoides on penis were also diagnosed, as an additional form
      of presentation to their generalized disease. Conclusions: In this study,
      inflammatory diseases were the most frequently diagnosed dermatoses, while SCC
      was the most common malignant tumor found. In the majority of psoriasis and
      lichen planus cases, clinical lesions were only present in the genital area.

PMID- 29644194
TI  - Safety and Efficacy of Different Systemic Treatment Modalities for Acute Pain of
      Herpes Zoster: A Pilot Study.
AB  - Background: Herpes zoster is a viral infection of skin caused by Varicella Zoster
      virus. The most important symptom for which the patient seeks medical advice is
      pain, which is perceived before the development of rash and lasts even after its
      resolution. The pain during the first 30 days after onset of herpes zoster is
      known as acute herpetic neuralgia. The aim of this study was to compare the
      efficacy and side-effects of different systemic treatment modalities for acute
      herpes zoster neuralgia. Materials and Methods: This was a randomized, single
      blind, parallel control study. Forty-five patients of herpes zoster within 72
      hours of onset were enrolled after considering various inclusion and exclusion
      criteria over a duration of 1 year. Pain severity was assessed after sequential
      distribution and allotment of patients in three groups using verbal rating scale
      (VRS). Patients in Group A (control group), were treated with Tab.valacyclovir (1
      g tds * 7 days), Group B-Tab.valacyclovir (1 g tds * 7 days) + Cap. Pregabalin
      (75 mg bd * 1 month), and Group C -Tab.valacyclovir (1 g tds * 7 days) +Cap.
      Pregabalin (75 mg bd * 1 month) + Tab.methylprednisolone (0.64 mg/kg body weight
      in two divided doses * 7 days). Patients were followed up at 1, 4, 6 weeks.
      Complete resolution of acute pain and side-effects were noted. Results: At the
      end of 4 weeks, reduction in acute pain was statistically significant (P < 0.05)
      in all the three groups individually compared to the baseline value. At the end
      of 6 weeks, percentage of patients with persistence of pain was more in Group A
      and B compared to Group C, which was statistically significant (P = 0.0001). In
      group A, postherpetic neuralgia was observed in more patients compared to group B
      and C. No significant side-effects were observed in any group except vomiting,
      somnolence, and dizziness. Limitations: Sample size of this study was limited.
      Further studies with large sample size are required to further validate the
      findings of the present study. Conclusions: Combination therapy with
      valacyclovir, methylprednisolone, and pregabalin has better efficacy compared to
      valacyclovir and pregabalin and valacyclovir alone in the management of acute
      herpes zoster neuralgia. No significant side-effects were observed.

PMID- 29644195
TI  - Nail Transillumination Combined with Dermoscopy for Enhancing Diagnosis of
      Subungual Hematoma.

PMID- 29644196
TI  - Multispectral Dermatoscopic Features of Chemical Leucoderma with Pigmented
      Contact Dermatitis.
AB  - Chemical leukoderma is characterized by pigment loss on constant exposure to
      chemical agents. Its association with pigmented contact dermatitis is rare. Here,
      we report a 40-year-old female presenting with depigmented macule with
      surrounding hyperpigmentation over the upper forehead. We used a multispectral
      dermatoscope by which decreased pigment network was better visualized with blue
      light, and gray granular dots were better appreciated with yellow light. Shorter
      wavelengths delineate epidermal features better whereas longer wavelengths
      highlight dermal features in multispectral dermatoscopy.

PMID- 29644197
TI  - Clinical Spectrum of Autoerythrocyte Sensitization Syndrome: A Series of Five
      Cases.
AB  - Autoerythrocyte sensitization syndrome (Gardner Diamond syndrome or GDS) is a
      rare syndrome characterized by painful and spontaneous purpura commonly affecting
      adult women, and is mostly associated with psychiatric illness. Diagnosis is
      mainly based on clinical presentation, exclusion of other simulating diseases,
      and psychiatric evaluation. Only few cases have been reported till date. We
      report five cases of spontaneous purpura with a normal investigation profile,
      except for iron deficiency anemia in 1 patient, of which three had associated
      underlying psychiatric illness. Autoerythrocyte sensitization test was positive
      in all our cases. Patients presenting with painful bruises without significant
      medical history such as underlying bleeding disorder or drug history or history
      of trauma should be considered for autoerythrocyte sensitization syndrome, and
      managed accordingly. The present study is a case series of patients with
      characteristic features of autoerythrocyte sensitization syndrome, considering
      the rarity of the reports on its clinical spectra.

PMID- 29644198
TI  - Olmsted Syndrome with Lateral Supraciliary Madarosis and Clubbing: A Rare Case
      Report.
AB  - Olmsted syndrome (OS) is a rare congenital, mutilating palmoplantar keratoderma
      first described by Olmsted in 1927. It starts in the neonatal period or in
      childhood, and has a slow but progressive disabling course. We report the case of
      a 16-year-old boy who presented with keratoderma of the palm and soles since
      childhood with lateral supraciliary madarosis and clubbing. The patient was
      started on oral retinoids and topical keratolytics and had partial improvement in
      2 months. Keratoderma of the palms and soles along with lateral supraciliary
      madarosis and clubbing in our case is a very rare finding, and to the best of our
      knowledge, has not been reported so far.

PMID- 29644199
TI  - Granuloma Annulare Skin Lesions in a Case of Sarcoidosis.
AB  - We report the case of a 32-year- old man with a short 3-week history of
      erythematous, annular, non scaly plaques on palmar and dorsal aspect of his
      hands, who was concurrently diagnosed as a case of sarcoidosis on the basis of
      findings of generalized lymphadenopathy and radiological and histological
      features of pulmonary sarcoidosis. His skin biopsy was consistent with the
      diagnosis of granuloma annulare. Sarcoidosis and granuloma annulare are two
      separate diseases, which involve the skin and have a mononuclear histiocytic
      cellular reaction, although their aetiology is still unknown. Granuloma annulare
      has been associated with the concomitant diagnosis of sarcoidosis in only two
      more case reports and this association can be evaluated further to study a common
      link in the aetipathogenesis of these two granulomatous skin diseases.

PMID- 29644200
TI  - Antifungal Efficacy of Amphotericin B against Dermatophytes and its Relevance in
      Recalcitrant Dermatophytoses: A Commentary.

PMID- 29644201
TI  - Behcet Disease in a Child: A Rare Disorder with an Unusual Complication and
      Favorable Outcome.

PMID- 29644202
TI  - Nasal Mucosal Dysplasia Induced by Topical Corticosteroids with Benzalkonium
      Chloride.

PMID- 29644203
TI  - Blaschkoid Angioma Serpiginosum: A Dermoscopic Diagnosis.

PMID- 29644204
TI  - Verrucous Disseminated Discoid Lupus Erythematosus with Plantar and Oral Lesions
      in the Absence of Systemic Lupus Erthyematosus.

PMID- 29644205
TI  - Pityriasis Rosea in a Mother and her Daughter: A Case Report.

PMID- 29644206
TI  - Growing Asymptomatic Nodule on the Ear.

PMID- 29644207
TI  - Through the Lens: Cryoglobulinemia.

PMID- 29644208
TI  - An "Abnormal" Hair Through the Dermoscope: Arthropod Body Part Mimicking a Hair.

PMID- 29644209
TI  - Use of Filters in Dermatoscopy to Capture Better Images.

PMID- 29644210
TI  - Dermoscopy of Hailey Hailey Disease.

PMID- 29644211
TI  - Dermoscopy of Angiokeratoma.

PMID- 29644212
TI  - Pigmentary Disorders and Their Management-Analyzing Current Evidence: Conference
      Proceedings and Learning Points. Pigmentarycon 2017. November 10-12, Indore,
      India.

PMID- 29644213
TI  - Immunotherapy Plus Cryotherapy: Potential Augmented Abscopal Effect for Advanced
      Cancers.
AB  - Since the 1920s the gold standard for treating cancer has been surgery, which is
      typically preceded or followed with chemotherapy and/or radiation, a process that
      perhaps contributes to the destruction of a patient's immune defense system.
      Cryosurgery ablation of a solid tumor is mechanistically similar to a vaccination
      where hundreds of unique antigens from a heterogeneous population of tumor cells
      derived from the invading cancer are released. However, releasing tumor-derived
      self-antigens into circulation may not be sufficient enough to overcome the
      checkpoint escape mechanisms some cancers have evolved to avoid immune responses.
      The potentiated immune response caused by blocking tumor checkpoints designed to
      prevent programmed cell death may be the optimal treatment method for the immune
      system to recognize these new circulating cryoablated self-antigens. Preclinical
      and clinical evidence exists for the complementary roles for Cytotoxic T
      lymphocyte-associated protein (CTLA-4) and PD-1 antagonists in regulating
      adaptive immunity, demonstrating that combination immunotherapy followed by
      cryosurgery provides a more targeted immune response to distant lesions, a
      phenomenon known as the abscopal effect. We propose that when the host's immune
      system has been "primed" with combined anti-CTLA-4 and anti-PD-1 adjuvants prior
      to cryosurgery, the preserved cryoablated tumor antigens will be presented and
      processed by the host's immune system resulting in a robust cytotoxic CD8+ T-cell
      response. Based on recent investigations and well-described biochemical
      mechanisms presented herein, a polyvalent autoinoculation of many tumor-specific
      antigens, derived from a heterogeneous population of tumor cancer cells, would
      present to an unhindered yet pre-sensitized immune system yielding a superior
      advantage in locating, recognizing, and destroying tumor cells throughout the
      body.

PMID- 29644215
TI  - Theoretical and NMR Conformational Studies of beta-Proline Oligopeptides With
      Alternating Chirality of Pyrrolidine Units.
AB  - Synthetic beta-peptides are potential functional mimetics of native alpha
      proteins. A recently developed, novel, synthetic approach provides an effective
      route to the broad group of beta-proline oligomers with alternating patterns of
      stereogenic centers. Conformation of the pyrrolidine ring, Z/E isomerism of beta
      peptide bonds, and hindered rotation of the neighboring monomers determine the
      spatial structure of this group of beta-proline oligopeptides. Preferences in
      their structural organization and corresponding thermodynamic properties are
      determined by NMR spectroscopy, restrained molecular dynamics and quantum
      mechanics. The studied beta-proline oligopeptides exist in dimethyl sulfoxide
      solution in a limited number of conformers, with compatible energy of formation
      and different spatial organization. In the beta-proline tetrapeptide with
      alternating chirality of composing pyrrolidine units, one of three peptide bonds
      may exist in an E configuration. For the alternating beta-proline pentapeptide,
      the presence of an E configuration for at least of one beta-peptide bond is
      mandatory. In this case, three peptide bonds synchronously change their
      configurations. Larger polypeptides may only exist in the presence of several E
      configurations of beta-peptide bonds forming a wave-like extended structure.

PMID- 29644216
TI  - Assessing Security Implications of Genome Editing: Emerging Points From an
      International Workshop.

PMID- 29644214
TI  - Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy,
      and Limitations.
AB  - Melanoma, a skin cancer associated with high mortality rates, is highly radio-
      and chemotherapy resistant but can also be very immunogenic. These circumstances
      have led to a recent surge in research into therapies aiming to boost anti-tumor
      immune responses in cancer patients. Among these immunotherapies, neutralizing
      antibodies targeting the immune checkpoints T-lymphocyte-associated protein 4
      (CTLA-4) and programmed cell death protein 1 (PD-1) are being hailed as
      particularly successful. These antibodies have resulted in dramatic improvements
      in disease outcome and are now clinically approved in many countries. However,
      the majority of advanced stage melanoma patients do not respond or will relapse,
      and the hunt for the "magic bullet" to treat the disease continues. This review
      examines the mechanisms of action and the limitations of anti-PD-1/PD-L1 and anti
      CTLA-4 antibodies which are the two types of checkpoint inhibitors currently
      available to patients and further explores the future avenues of their use in
      melanoma and other cancers.

PMID- 29644218
TI  - Nutrition in the Bin: A Nutritional and Environmental Assessment of Food Wasted
      in the UK.
AB  - The UK currently has the most detailed, directly measured data for food wasted in
      the home. This includes information on the exact types of food wasted. These data
      allow calculation of the nutrients within that waste, as well as its
      environmental impact. The results progress the conversation beyond how much food
      is wasted or its energy content; it permits the implications for nutrition and
      sustainability to be assessed in detail. Data for UK household food waste were
      expressed as an average waste per capita for each type of food. Each food type
      was matched with an item (or group of items) from the UK Composition of Foods
      (7th Ed). The level of nutrients wasted was compared to UK Reference Nutrient
      Intakes (RNIs) for adult women (19-50 years, used as a proxy for general
      population requirements). The data were normalized into "nutrient days" wasted
      per capita per year, then into the number of complete diet days (for 21 nutrients
      plus energy). Results show that approximately 42 daily diets were discarded per
      capita per year. By individual nutrient, the highest losses were vitamin B12,
      vitamin C, and thiamin (160, 140, and 130 nutrient days/capita/year,
      respectively). For protein, dietary energy and carbohydrates, 88, 59, and 53
      nutrient days/capita/year, respectively, were lost. Substantial losses were also
      found for under-consumed nutrients in the UK: calcium, which was mostly lost via
      bakery (27%) and dairy/eggs (27%). Food folate was mainly lost through fresh
      vegetables/salads (40%) and bakery (18%), as was dietary fiber (31 and 29%,
      respectively). Environmental impacts were distributed over the food groups, with
      wasted meat and fish the single largest contribution. For all environmental
      impacts studied, the largest contribution came from agricultural production. This
      paper shows that there are areas where interventions preventing food waste and
      promoting healthy eating could work together (e.g., encouraging consumption of
      vegetables or tackling overbuying, especially of unhealthy foods). Food
      manufacturers and retailers, alongside governments and NGOs, have a key role to
      minimize waste of environmentally impactful, nutrient-dense foods, for instance,
      by helping influence people's behaviors with appropriate formulation of products,
      packaging, portioning, use of promotions, or public education.

PMID- 29644217
TI  - Sensing the Stress: A Role for the UPRmt and UPRam in the Quality Control of
      Mitochondria.
AB  - Mitochondria exist as compartmentalized units, surrounded by a selectively
      permeable double membrane. Within is contained the mitochondrial genome and
      protein synthesis machinery, required for the synthesis of OXPHOS components and
      ultimately, ATP production. Despite their physical barrier, mitochondria are
      tightly integrated into the cellular environment. A constant flow of information
      must be maintained to and from the mitochondria and the nucleus, to ensure
      mitochondria are amenable to cell metabolic requirements and also to feedback on
      their functional state. This review highlights the pathways by which
      mitochondrial stress is signaled to the nucleus, with a particular focus on the
      mitochondrial unfolded protein response (UPRmt) and the unfolded protein response
      activated by the mistargeting of proteins (UPRam). Although these pathways were
      originally discovered to alleviate proteotoxic stress from the accumulation of
      mitochondrial-targeted proteins that are misfolded or unimported, we review
      recent findings indicating that the UPRmt can also sense defects in mitochondrial
      translation. We further discuss the regulation of OXPHOS assembly and speculate
      on a possible role for mitochondrial stress pathways in sensing OXPHOS
      biogenesis.

PMID- 29644219
TI  - Management of Chemotherapy-Induced Left Ventricular Dysfunction and Heart Failure
      in Patients With Cancer While Undergoing Cancer Treatment: The MD Anderson
      Practice.
AB  - Chemotherapy-induced cardiotoxicity resulting in heart failure (HF) is one of the
      most dreaded complications of cancer therapy that can significantly impact
      morbidity and mortality. With a high prevalence of cardiovascular disease in
      cancer patients, the risk of developing HF is significantly increased. A new
      discipline of Onco-Cardiology has evolved to address the cardiovascular needs of
      patients with cancer, however, there is limited evidence-based data to guide
      clinical decision-making in the management of the cardiovascular complications of
      cancer therapy. The department of cardiology at MD Anderson Cancer Center
      initiated the MD Anderson Practice (MAP) project and developed algorithms to
      guide the management of the cardiovascular complications of cancer therapy. For
      chemotherapy-induced HF, we initiated the Heart Success Program (HSP), a patient
      centered program that promotes interdisciplinary collaboration for the management
      of concurrent HF resulting from chemotherapy-induced cardiotoxicity. After one
      year of HSP implementation, compliance with the Center for Medicare and Medicaid
      Services HF core measures has significantly improved. The measurement of LVEF and
      initiation of recommended pharmacologic therapy for HF (angiotensin converting
      enzyme inhibitor [ACE-I] or angiotensin receptor blocker for ACE-I intolerant
      patients) has improved to 100%; provision of discharge instruction has improved
      from 50 to 94%; and the 30-day hospital readmission rate decreased from 40 to
      27%. This article will describe the MD Anderson Practice in the management of
      chemotherapy-induced cardiomyopathy and HF in cancer patients through the HSP.
      The novelty of the HSP has raised clinician's awareness of the magnitude of the
      clinical problem of HF in cancer and the.

PMID- 29644220
TI  - Can Blood Biomarkers Help Predicting Outcome in Transcatheter Aortic Valve
      Implantation?
AB  - Transcatheter aortic valve implantation (TAVI) has become the method of choice
      for patients with severe aortic valve stenosis, who are ineligible or at high
      risk for surgery. In this high risk patient population, early and late mortality
      and rehospitalization rates after TAVI are still relatively high. In spite of
      recent improvements in procedural TAVI, and establishment of risk models for poor
      outcome, determining individual risk remains challenging. In this context,
      current data from several small studies strongly suggest that blood biomarkers of
      myocardial injury, cardiac mechanical stretch, inflammation, and hemostasis
      imbalance might play an important role by providing informations on patient risk
      at baseline, and postprocedural progression of patient clinical conditions from
      days up to years post-TAVI. Although the role of biomarkers for predicting
      survival post-TAVI remains to be validated in large randomized studies,
      implementing biomarkers in clinical practice might improve risk stratification,
      thereby further reducing TAVI-associated morbidity and mortality.

PMID- 29644222
TI  - Galileo Galilei: Science vs. faith.

PMID- 29644223
TI  - Torsade de pointes and systemic azole antifungal agents: Analysis of global
      spontaneous safety reports.
AB  - Background: Literature about torsade de pointes induced by azole antifungal
      agents is scarce, despite the well-known association. Furthermore, little is
      known about the latency time between commencing an azole antifungal agent and
      developing torsade de pointes. The objectives of the present study were therefore
      to identify all cases of torsade de pointes associated with systemic azole
      antifungal use reported to the WHO monitoring centre (Uppsala, Sweden) and to
      determine the latency times between commencing the azole and developing torsade
      de pointes. Methods: Investigator-driven, retrospective, descriptive analysis of
      post-marketing pharmacovigilance data regarding systemic azole antifungal agents
      and the development of torsade de pointes reported to the WHO monitoring centre
      1995-2015. Results: 191 cases were reported as follows: fluconazole 130,
      itraconazole 22, ketoconazole 5, posaconazole 1, voriconazole 33. More than half
      of all cases involved concomitant suspected or interacting drugs. The median
      latency times between starting the azole and developing torsade de pointes ranged
      from 1 (posaconazole) - 9.5 days (itraconazole), range <1-250). Conclusions:
      Clinicians should be aware of these features of azole-associated torsade de
      pointes, avoid interacting drugs if at all possible and monitor at-risk patients.

PMID- 29644221
TI  - Physiologic Factors Influencing the Arterial-To-End-Tidal CO2 Difference and the
      Alveolar Dead Space Fraction in Spontaneously Breathing Anesthetised Horses.
AB  - The arterial to end-tidal CO2 difference (P(a-ET)CO2) and alveolar dead space
      fraction (VDalvfrac = P(a-ET)CO2/PaCO2), are used to estimate Enghoff's
      "pulmonary dead space" (V/QEng), a factor which is also influenced by venous
      admixture and other pulmonary perfusion abnormalities and thus is not just a
      measure of dead space as the name suggests. The aim of this experimental study
      was to evaluate which factors influence these CO2 indices in anesthetized
      spontaneously breathing horses. Six healthy adult horses were anesthetized in
      dorsal recumbency breathing spontaneously for 3 h. Data to calculate the CO2
      indices (response variables) and dead space variables were measured every 30 min.
      Bohr's physiological and alveolar dead space variables, cardiac output (CO), mean
      pulmonary pressure (MPP), venous admixture [Formula: see text], airway dead
      space, tidal volume, oxygen consumption, and slope III of the volumetric
      capnogram were evaluated (explanatory variables). Univariate Pearson correlation
      was first explored for both CO2 indices before V/QEng and the explanatory
      variables with rho were reported. Multiple linear regression analysis was
      performed on P(a-ET)CO2 and VDalvfrac assessing which explanatory variables best
      explained the variance in each response. The simplest, best-fit model was
      selected based on the maximum adjusted R2 and smallest Mallow's p (Cp). The R2 of
      the selected model, representing how much of the variance in the response could
      be explained by the selected variables, was reported. The highest correlation was
      found with the alveolar part of V/QEng to alveolar tidal volume ratio for both,
      P(a-ET)CO2 (r = 0.899) and VDalvfrac (r = 0.938). Venous admixture and CO best
      explained P(a-ET)CO2 (R2 = 0.752; Cp = 4.372) and VDalvfrac (R2 = 0.711; Cp =
      9.915). Adding MPP (P(a-ET)CO2) and airway dead space (VDalvfrac) to the models
      improved them only marginally. No "real" dead space variables from Bohr's
      equation contributed to the explanation of the variance of the two CO2 indices.
      P(a-ET)CO2 and VDalvfrac were closely associated with the alveolar part of V/QEng
      and as such, were also influenced by variables representing a dysfunctional
      pulmonary perfusion. Neither P(a-ET)CO2 nor VDalvfrac should be considered
      pulmonary dead space, but used as global indices of V/Q mismatching under the
      described conditions.

PMID- 29644224
TI  - Pharmacological management of perioperative bleeding in cardiac surgery.

PMID- 29644225
TI  - FOURIER & PCSK9 RNAi: Towards enhancing durability and efficacy of PCSK9
      inhibitors.

PMID- 29644227
TI  - Pathologic confirmation of valve thrombosis detected by four-dimensional computed
      tomography following valve-in-valve transcatheter aortic valve replacement.
AB  - A major concern regarding transcatheter aortic valve replacement (TAVR) is
      leaflet thrombosis. Four-dimensional computed tomography (4D-CT) is the preferred
      imaging modality to evaluate patients with suspected valve thrombosis. To date,
      the abnormal findings visualized by 4D-CT suggestive of leaflet thrombosis have
      lacked pathologic confirmation from a surgically explanted valve in a surviving
      patient. Herein, we provide pathologic confirmation of thrombus formation
      following surgical explantation of a thrombosed TAVR prosthesis that was
      initially identified by 4D-CT.

PMID- 29644228
TI  - How are countries dealing with their current cardio-vascular disease burden? A
      snapshot from the WHO Eastern Mediterranean Region (EMR).
AB  - In recent years, a number of global commitments have been made in the area of
      noncommunicable diseases (NCD). These include the UN NCD Political Declaration in
      2011, and the UN Comprehensive Review on NCDs and Outcome Document in 2014. Nine
      global targets have been agreed in the area of NCDs, and NCDs have been addressed
      in the Sustainable Development Goals (SDG). Another UN high-level meeting will
      take place in September 2018 to assess country progress across the globe. At the
      regional level, a number of initiates have taken place to deliver on these global
      commitments. One of the guiding documents is the Regional Framework for Action on
      Noncommunicable Diseases. This framework was endorsed at the WHO EM Regional
      Committee in 2012, and includes 17 strategic interventions and 10 monitoring
      indicators, covering the areas of NCD governance, prevention, surveillance and
      healthcare. Progress is being monitored on an annual basis through the
      development of country progress factsheets and biennial WHO Country Capacity
      Survey on NCDs. To date however, progress has been insufficient and uneven.
      Moreover, is has been slowest in the areas of planning and surveillance, and
      tobacco control. No uniform approach or model exists for all EMR countries, but a
      number of countries have advanced their national NCD agenda through original and
      innovative initiatives. Perceived challenges include the uneven progress and
      needs across the WHO EM region, humanitarian emergencies and political
      instability, vertical approaches, a lack of human and financial resources and
      other health systems weaknesses. Opportunities however exist through the global
      SDG and universal health coverage (UHC) agendas offering an opportunity to
      revisit essential health services package until 2030. Overall, there has been
      political commitment to NCD governance, as evidenced by the EM Regional
      Committee's endorsement of the regional framework for action. However, despite
      the clear roadmap, progress has been slow and scattered, differing vastly by
      country and by topic. We recommend that countries urgently scale up their efforts
      in all four areas of the EM Regional Framework of Action to be able to achieve
      their national and international targets.

PMID- 29644226
TI  - Nitric oxide and pulmonary arterial hypertension.
AB  - The pathogenesis of pulmonary arterial hypertension remains undefined. Changes in
      the expression and effects mediated by a number of vasoactive factors have been
      implicated to play a role in the onset and progression of the disease. The source
      of many of these mediators, such as nitric oxide (NO), prostacyclin and
      endothelin-1 (ET-1), is the pulmonary endothelium. This article focus in the role
      of nitric oxide in PAH, reviewing the evidence for its involvement in regulation
      of pulmonary a vascular tone under physiological conditions, the mechanisms by
      which it can contribute to the pathological changes seen in PAH and strategies
      for the use of NO as a therapy for treatment of the disease.

PMID- 29644229
TI  - CANTOS: A breakthrough that proves the inflammatory hypothesis of
      atherosclerosis.
AB  - Atherosclerosis is no longer considered solely a disorder of subintimal
      deposition of modified low-density lipoprotein particles in the arterial wall.
      Rather, it is known to be a chronic inflammatory disorder. No evidence has shown
      that reducing vascular inflammation in the absence of concomitant lowering of
      lipoproteins levels reduces the rates of adverse cardiovascular (CV) events.
      Canakinumab, a fully human monoclonal antibody that neutralizes interleukin (IL)
      1beta, significantly reduced the rate of recurrent CV events in patients with
      prior myocardial infarction in the Canakinumab Anti-inflammatory Thrombosis
      Outcome Study (CANTOS). Canakinumab has no effect on CV or all-cause mortality,
      however it was associated with high incidence of fatal infections. Thus, the net
      benefit needs to be properly addressed in future studies that evaluate the
      potential benefit of the anti-inflammatory therapies and whether it can change
      clinical practice in the near future.

PMID- 29644230
TI  - NOBLE and EXCEL: The debate for excellence in dealing with left main stenosis.
AB  - Left main coronary artery (LMCA) disease is associated with increased morbidity
      and mortality. Coronary artery bypass grafting surgery (CABG) has always been the
      standard revascularization strategy for this group of patients. However, with the
      recent developments in stents design and medical therapy over the past decade,
      several trials have been designed to evaluate the safety and efficacy of
      percutaneous coronary intervention (PCI) as an alternative to CABG surgery in
      patients with LMCA disease. Recently, the results of two major trials, EXCEL and
      NOBLE, comparing CABG versus PCI in this patient population have been released.
      In fact, the results of both trials might appear contradictory at first glance.
      While the EXCEL trial showed that PCI was non-inferior to CABG surgery, the NOBLE
      trial suggested that CABG surgery is a better option. In the following review, we
      will discuss some of the similarities and contrasts between these two trials and
      conclude with lessons to be learned to our daily practice.

PMID- 29644231
TI  - Mechanistic insights of the left ventricle structure and fibrosis in the
      arrhythmogenic mitral valve prolapse.
AB  - Mitral valve prolapse (MVP) is a common and benign condition. However, some
      anatomic forms have been recently associated with life-threatening ventricular
      arrhythmias and sudden cardiac death. Imaging MVP holds the promise of
      individualized MVP risk assessment. Noninvasive imaging techniques available
      today are playing an increasingly important role in the diagnosis, prognosis and
      monitoring of MVP. In this article, we will review the current evidence on
      arrhythmogenic MVP, with special focus on the utility of echocardiography and CMR
      for identifying benign and "malignant" forms of MVP. The clinical relevance of
      this manuscript lies in the value of imaging technology to improve MVP risk
      prediction, including those arrhythmic-MVP cases with a higher risk of sudden
      cardiac death.

PMID- 29644233
TI  - Prevalence, awareness, treatment, control and risk factors associated with
      hypertension in Lebanese adults: A cross sectional study.
AB  - Background: The prevention and control of hypertension is an essential component
      for reducing cardiovascular disease burden. Hypertension is an important public
      health issue, yet few studies have examined its current status among the Lebanese
      population. Objective: To examine the prevalence, awareness, treatment and
      control of hypertension and its associated risk factors among Lebanese adults.
      Methods: A cross-sectional study was conducted between December 2014, and May
      2015, on adults from the five districts of Lebanon. Multistage sampling was used
      to enroll participants. Hypertension was defined as an average of two blood
      pressure (BP) measurements with systolic/diastolic blood pressure of at least
      140/90 mm Hg, using an automated digital device, or the use of antihypertensive
      medication. A questionnaire was used to assess hypertension risk factors,
      awareness, treatment and control. Results: Of the 1362 Lebanese adults
      interviewed, 399 (29.3%) had hypertension. Of these, 106 (26.5%) were aware of
      their condition. Sixty-nine patients (65%) of those aware, were receiving
      treatment, and 38 (55%) participants from those treated were controlled. The
      significant risk factors were sex, gender, age, family history of hypertension,
      obesity, and a low level of education. Conclusions: Hypertension is prevalent
      among the Lebanese adult population and is multifactorial, but remains
      incompletely recognized, leading to insufficient control. Hypertension was highly
      prevalent in males in the age category 18-29 years. These findings show that
      improvements in detection, treatment, and control of hypertension among Lebanese
      adults, is much needed.

PMID- 29644232
TI  - Individualizing immunosuppression in lung transplantation.
AB  - Immunosuppression management after lung transplantation continues to evolve, with
      an increasing number of agents available for use in various combinations allowing
      for more choice and individualization of immunosuppressive therapy. Therapeutic
      developments have led to improved outcomes including lower acute rejection rates
      and improved survival. However, a one size fits all approach for any
      immunosuppressive strategy may not be best suited to the individual patient and
      ultimately patient specific factors must be considered when designing the
      immunosuppressive regimen. Recipient factors including age, race, co-morbidities,
      immunologic risk, genetic polymorphisms, concomitant and previous
      pharmacotherapy, and overall immunosuppression burden should be considered. There
      are several significant drug-drug interactions with select immunosuppressive
      agents utilized in lung transplant pharmacotherapy that must be considered when
      choosing and devising a dosing strategy for an individual immunosuppressive
      agent. Herein, considerations for immunosuppression management in the individual
      patient will be reviewed.

PMID- 29644234
TI  - Modelling coronary flow after the Norwood operation: Influence of a suggested
      novel technique for coronary transfer.
AB  - Background: The dynamic behavior of the aortic sinuses has an important function
      in the specific characteristics of coronary blood flow. Several publications have
      confirmed suboptimal myocardial perfusion after the Norwood procedure. Our study
      was undertaken to confirm four hypotheses. First, we hypothesized that there is
      more resistance to coronary flow due to coronary attachments to hypoplastic
      aortic root and sinuses. Also, as the amalgamation of the ascending aorta with
      the pulmonary artery occurs above the aortic root, the coronary blood flow is not
      fully in antegrade pattern. Second, performing the Norwood with our modification
      i.e., coronary transfer to the well-developed sinuses of the pulmonary root will
      result in less resistance to flow and a full antegrade flow pattern. This may
      eventually improve the long term ventricular and survival outcomes. Third, our
      modification is applicable to all procedures where the pulmonary root supplies
      the systemic circulation e.g., Norwood, Damus-Kaye-Stansel (DKS), and Yasui
      operations, whether applied to single or biventricular repair. Fourth, with our
      modification, the effect of the type of shunt; Sano vs. Blalock Taussig (BT
      shunt) on the coronary flow after the Norwood will be mitigated. This will give
      the surgeon more freedom to which shunt to use, and may make the surgeon keener
      to perform the BT shunt in order to avoid the ventricular scar associated with
      the Sano shunt which will negatively impact the ventricular function. Methods:
      Computational fluid dynamic (CFD) simulations were performed to evaluate flow
      streamlines and to quantify flow distribution and total pressure drop in the
      coronary branches in both Norwood (pre-transfer) and modified Norwood (post
      transfer) models. Comparisons between the two models were performed. Results: The
      systolic flow rate in all coronary branches was higher in the post-transfer model
      in the proportions of: left main 5%, left anterior descending (LAD) 6%, left
      circumflex (LCx) 3.5%, and right coronary artery (RCA) 7.2% higher flow rates. In
      diastole, pressure drop from the aortic inlet to distal left main and distal
      right main was substantially less in the post-transfer model. Conclusion: Post
      transfer model has produced more favorable coronary hemodynamics in all coronary
      branches. As a result, performing our modification could potentially improve the
      long term ventricular and survival outcomes.

PMID- 29644235
TI  - Endograft rescue of compromised interposition aortic graft in an adult patient
      with congenital heart disease.
AB  - In a 19-year-old male with interrupted aortic arch and complex congenital heart
      disease, we report percutaneous repair of a compromised aortic conduit. The
      patient had aortic arch repair in childhood utilizing a 12 mm Hemashield Dacron
      conduit. CT angiography showed multiple segments of this conduit were dilated to
      16 mm suggesting conduit degeneration and failure with pseudoaneurysm formation.
      We utilized a self-expanding aortic endograft supported by internal placement of
      bare metal stents to repair the conduit. Our repair was guided by 3D rotational
      angiography. This adult patient with complex congenital heart disease and
      interrupted aortic arch is an example of patients in whom endograft repair of
      compromised aortic conduits presents a much lower risk alternative than surgical
      revision.

PMID- 29644236
TI  - Hypertrophic cardiomyopathy with a large apical ventricular aneurysm and mural
      thrombus.
AB  - Hypertrophic cardiomyopathy (HCM) is characterized by increased left ventricular
      wall thickness in the absence of any other identifiable cause of thickness. It
      predisposes the patient to increased risk of sudden cardiac death (SCD) due to
      fatal arrhythmias. Approximately 2% of the HCM patients have left ventricular
      apical aneurysm. CMR imaging is better in identifying this apical aneurysm as
      compared to echocardiogram. This apical aneurysm, which can be akinetic or
      dyskinetic, increases the risk of disease-related adverse events as compared to
      general HCM. These adverse disease-related events include SCD, thromboembolism,
      and symptoms of heart failure. We report a rare case of hypertrophic
      cardiomyopathy in association with Williams-Beuren Syndrome. On CMR imaging,
      patient was found to have a large apical aneurysm and mid-ventricular obstruction
      with underlying thrombus. He was started on oral anticoagulation, and ICD was
      recommended.

PMID- 29644237
TI  - Stress, Depression, and Occupational Injury among Migrant Farmworkers in
      Nebraska.
AB  - Agriculture is one of the most dangerous industries in the United States.
      Farmworkers, including migrant farmworkers, are at risk for work-related
      injuries. This study explores the association between stress, depression, and
      occupational injury among migrant farmworkers in Nebraska. Occupational injury
      was hypothesized to significantly increase the odds of farmworkers being stressed
      and depressed. Two hundred migrant farmworkers (mean age = 33.5 years, standard
      deviation (SD) = 12.53; 93.0% men, 92.9% of Mexican descent) were interviewed. In
      bivariate analyses, results indicated that stress and depression were positively
      associated with occupational injury. Two logistic regression models were
      developed. Occupational injury was a significant factor for depression, but not
      for stress. Participants who had been injured on the job were over seven times
      more likely to be depressed. These results highlight the interconnection between
      the work environment and mental health. More must be done to foster well-being in
      rural, agricultural communities. Improving occupational health and safety
      information and training, integrating behavioral health services into primary
      care settings, and strengthening the protections of the Migrant and Seasonal
      Agricultural Worker Protection Act may improve conditions for migrant farmworkers
      in the rural Midwest.

PMID- 29644238
TI  - Mechanisms of Optical Regression Following Corneal Laser Refractive Surgery:
      Epithelial and Stromal Responses.
AB  - Laser vision correction is a safe and effective method of reducing spectacle
      dependence. Photorefractive Keratectomy (PRK), Laser In Situ Keratomileusis
      (LASIK), and Small-Incision Lenticule Extraction (SMILE) can accurately correct
      myopia, hyperopia, and astigmatism. Although these procedures are nearing
      optimization in terms of their ability to produce a desired refractive target,
      the long term cellular responses of the cornea to these procedures can cause
      patients to regress from the their ideal postoperative refraction. In many cases,
      refractive regression requires follow up enhancement surgeries, presenting
      additional risks to patients. Although some risk factors underlying refractive
      regression have been identified, the exact mechanisms have not been elucidated.
      It is clear that cellular proliferation events are important mediators of optical
      regression. This review focused specifically on cellular changes to the corneal
      epithelium and stroma, which may influence postoperative visual regression
      following LASIK, PRK, and SMILE procedures.

PMID- 29644239
TI  - The Correlation between Changes in Biochemical Parameters and Central Macular
      Thickness in Patients with Non-Proliferative Diabetic Retinopathy.
AB  - This study aimed at evaluating the correlation between changes in Hemoglobin A1c
      (HbA1c) and fasting serum lipids, and Central Macular Thickness (CMT) in patients
      with Non-Proliferative Diabetic Retinopathy (NPDR). In the current research, both
      eyes of 68 patients with mild or moderate NPDR, without clinically significant
      macular edema, were studied. Levels of fasting serum lipids, HbAlc, and CMT were
      measured during the first visit and at the end of the follow-up period (3
      months). For statistical analysis, CMTs of each eye were studied and the
      correlation of changes was investigated. Additionally, the direction of changes
      in CMT for each eye was determined, and whether the changes in both eyes were
      symmetrical was investigated. Out of 68 patients, 24 were male and 44 were
      female. The mean CMT of all eyes was 290.05 +/- 48.90 um during the first visit
      and 286.80 +/- 37.57 um on the 3rd month follow-up. The mean HbAlc was 8.71 +/-
      1.82% at first visit to the hospital and the mean HbAlc was 8.39 +/- 1.65% at the
      final visit. Although the changes in HbA1c and CMT during the follow-up period
      were statistically insignificant, the correlation of these 2 values was
      statistically significant (p=0.01). However, amongst l3 patients, the CMTs were
      asymmetrically changed in each eye during the follow-up period. To the best of
      the author's knowledge, this was the first study, which indicated a significant
      correlation in changes of CMT and HbA1c, even amongst patients with low-grade
      diabetic retinopathy. Demonstration of asymmetric changes in CMT of each
      treatment-naive eye of the same patient, during changes in systemic conditions,
      was another important finding of this study.

PMID- 29644240
TI  - Consanguineous Marriage as a Risk Factor for Developing Keratoconus.
AB  - Heredity plays an important role in keratoconus (KC). Consanguineous marriage
      (CM) can affect the transmission of recessively inherited conditions. We aimed to
      investigate the role of consanguineous marriage in the development of KC. This
      study included two groups: the first group comprised 415 patients who underwent
      surgery for KC for the first time at Khalili University Hospital (Shiraz, Iran),
      between 2010 and 2014; the second group comprised 415 healthy individuals who
      served as age- and sex-matched controls for the patient group. All study subjects
      were from the Fars province in Iran. CM type was evaluated by a standard
      checklist in both groups. The mean inbreeding coefficient (alpha) was evaluated
      and compared between the two groups. The percentage of parental first-cousin
      marriages was 35.4% in the patient group and 18.3% in the control group. The mean
      inbreeding coefficient (alpha) was 0.0291 in the patient group and 0.0135 in the
      control group. Patients with KC had a significantly higher mean inbreeding
      coefficient (alpha) than controls (T = 8, df = 828, P < 0.001). Our study
      suggests that CM can play a role in the pathogenesis of KC. As this disease is
      among the most frequent ocular disorders in our country, CM should be considered
      by health care systems within their screening programs.

PMID- 29644241
TI  - Striped Circle Visual Acuity Chart; A Novel Visual Acuity Chart Based on the
      Landolt-C Chart.
AB  - Measurement of Visual Acuity (VA) has been used for eye examinations under
      various clinical conditions. In addition, because of changes in VA with a range
      of eye diseases, its measurement is used to screen, diagnose, and evaluate
      response to treatment in numerous eye diseases and predict the patient's visual
      function. VA and the likelihood of astigmatism could be evaluated simultaneously
      using a newly designed Stripped Circle (SC) VA chart. This chart has been
      developed based on the standard VA measurement scale chart, and the Landolt-C
      (LC) VA chart and all the standards for a VA chart design were implemented during
      its development. However, to publicize the clinical application of this VA
      measurement chart, further studies are required to evaluate its sensitivity,
      specificity, and repeatability compared with a similar standard VA chart.

PMID- 29644242
TI  - The Association between TGF-beta1 G915C (Arg25Pro) Polymorphism and the
      Development of Primary Open Angle Glaucoma: A Case-Control Study.
AB  - The purpose of the current study was to identify the potential association
      between Single Nucleotide Polymorphism (SNP) TGFbeta1 +915 (C or G) in codon 25
      and Primary Open Angle Glaucoma (POAG). Overall, 88 cases with POAG and a control
      group of 52 healthy individuals were recruited from the First Ophthalmology
      Department of Athens University. DNA was isolated from whole blood samples and
      genotype frequencies for the polymorphism rs1800471 (G915C, Arg25Pro) of the TGF
      beta1 gene were assessed. Genotype distribution frequencies for the polymorphism
      rs1800471 (G915C, Arg25Pro) of the TGF-beta1 gene were not statistically
      different between patients with POAG and control subjects. The present study
      failed to determine any significant genotypic association with POAG, despite the
      fact that the presence of the C allele was scarcely increased in the POAG when
      compared with the control group.

PMID- 29644243
TI  - Comparison of Visual, Refractive and Aberration Measurements of INTACS versus
      Toric ICL Lens Implantation; A Four-year Follow-up.
AB  - This study was performed to evaluate the visual, refractive, and aberration
      measurement results of 2 implants, including Intacs Intracorneal Ring Segments
      (ICRS) and phakic Toric Implantable Collamer Lens (TICL), in patients with
      moderate Keratoconus (KCN). In this retrospective cross-sectional study, 30
      patients with KCN with a mean age of 29.83 years were included in 2 groups,
      including the Intacs Intracorneal Ring Segments (ICRS) group and the phakic Toric
      Implantable Collamer Lens (TICL) group. Preoperative data as well as 6-month, 1-,
      2-, 3- and 4-year follow-up data after the operation were collected and analyzed
      with the SPSS software (ver. 23.0, SPSS, Inc., Chicago, IL), using the paired t
      test, independent t-test, repeated measures Analysis of Variance (ANOVA), and one
      way ANOVA. This study included 30 patients with KCN with a mean age of 29.83
      years and range of 25 to 35 years, including 17 males with a mean age of 30.11
      years and 13 female with a mean age of 29.25 years. Except for preoperative
      Uncorrected Distance Visual Acuity (UCDVA), Spherical Equivalent (SE) and
      astigmatism, there was a significant difference between the 2 groups regarding
      other variables. The TICL group had a significantly better UCDVA and Best
      Corrected Distance Visual Acuity (BCDVA) in all post-operative follow-ups, and SE
      and astigmatism values were significantly lower in all post-operative follow-ups
      when compared with the ICRS group. There was a significant reduction in corneal
      and total coma as well as internal trefoil aberrations (P<0.01, P<0.01, and
      P=0.014, respectively) in the ICRS group, and TICL led to a significant reduction
      in internal trefoil aberration with P<0.03. Comparison of the 2 groups revealed a
      significant difference in corneal spherical (P<0.01) and total coma (P=0.02)
      aberrations and no significant differences in other HOA. Both ICRS and TICL are
      useful in patients with moderate KCN. However, TICL appears to have more stable
      and predictable vision results.

PMID- 29644244
TI  - Knowledge and Awareness of Glaucoma in Subjects with Glaucoma and their Normal
      First-Degree Relatives.
AB  - The objective of this study was to assess knowledge and awareness of glaucoma in
      subjects with glaucoma and their normal first-degree relatives. Awareness and
      knowledge of glaucoma were compared between each patient and his/her relative. We
      designed a questionnaire containing a set of brief and structured questions to
      gather information regarding the participants' demographics and knowledge and
      awareness of glaucoma. There were two groups in this study. The first group
      ("glaucoma" group) comprised patients diagnosed with glaucoma, while the second
      group ("relatives" group) consisted of the first-degree relatives of the
      patients. Ninety-one participants aged over 40 years (mean, 48.5 years) filled
      the questionnaire. Thirty-four participants belonged to the glaucoma group, while
      the remaining were first-degree relatives of the patients. According to the
      responses obtained, 26 (76%) participants in the glaucoma group and 47 (82%)
      participants in the relatives group had heard of the term "glaucoma." There were
      no statistically significant differences related to age or gender in glaucoma
      awareness. Glaucoma awareness was positively associated with education level in
      both groups (p < 0.0001). The definition of "glaucoma" in the glaucoma group and
      the relatives group was known to 20 (58.8%) and 17 (29.8%) participants,
      respectively, and the difference was statistically significant (p < 0.0001). The
      adjusted odds ratios for awareness and knowledge of glaucoma were 75.2 (95%
      confidence interval [CI], 11.80 to 366.65) and 148.7 (95% CI, 14.07 to 1646.52),
      respectively, for individuals with a university graduate level of education. In
      our study, education level was the only demographic indicator that was a
      predictor of knowledge and awareness of glaucoma. While more scientific evidence
      is obtained, community education with focus on the promotion of knowledge and
      awareness of glaucoma would be a practical public health strategy, especially for
      individuals aged more than 40 years with a family history of glaucoma.

PMID- 29644245
TI  - Acute Onset of Pneumococcal Pneumonia Following Instrumentation of the
      Respiratory Tract.
AB  - We describe 22 patients who developed pneumococcal pneumonia within 96 hours of
      respiratory tract instrumentation. In 59% of cases, the time to onset of symptoms
      was <24 hours. Instrumentation bypasses normal protective barriers and carries
      organisms directly to the lower airways, leading to the rapid development of
      pneumonia.

PMID- 29644246
TI  - Hepatitis C Treatment Outcomes for People Who Inject Drugs Treated in an
      Accessible Care Program Located at a Syringe Service Program.
AB  - Hepatitis C virus (HCV) is a significant public health problem that
      disproportionately afflicts people who inject drugs. We describe outcomes of HCV
      treatment co-located within a syringe services program (SSP). Fifty-three
      participants started therapy, and 91% achieved sustained virologic response. SSPs
      provide an effective venue for HCV treatment.

PMID- 29644248
TI  - MRI and PET-CT Failed to Differentiate Between Hepatic Malignancy and Brucelloma.
AB  - Brucellosis is a common, worldwide zoonosis. Clinical presentation is protean and
      often goes unrecognized. Hepatic brucelloma is a rare local complication of
      chronic brucellosis. We report a case in which magnetic resonance imaging and
      positron emission tomography imaging prompted suspicion of a hepatic malignancy.
      Diagnosis was ultimately made by serology and polymerase chain reaction of
      resected liver tissue.

PMID- 29644247
TI  - Quantification of Torque Teno Virus and Epstein-Barr Virus Is of Limited Value
      for Predicting the Net State of Immunosuppression After Lung Transplantation.
AB  - Background: Major hurdles for survival after lung transplantation are rejections
      and infectious complications. Adequate methods for monitoring immune suppression
      status are lacking. Here, we evaluated quantification of torque teno virus (TTV)
      and Epstein-Barr virus (EBV) as biomarkers for defining the net state of
      immunosuppression in lung-transplanted patients. Methods: This prospective single
      center study included 98 patients followed for 2 years after transplantation.
      Bacterial infections, fungal infections, viral respiratory infections (VRTI),
      cytomegalovirus (CMV) viremia, and acute rejections, as well as TTV and EBV
      levels, were monitored. Results: The levels of torque teno virus DNA increased
      rapidly after transplantation, likely due to immunosuppressive treatment. A
      modest increase in levels of Epstein-Barr virus DNA was also observed after
      transplantation. There were no associations between either TTV or EBV and
      infectious events or acute rejection, respectively, during follow-up. When
      Tacrolimus was the main immunosuppressive treatment, TTV DNA levels were
      significantly elevated 6-24 months after transplantation as compared with
      Cyclosporine treatment. Conclusions: Although replication of TTV, but not EBV,
      appears to reflect the functionality of the immune system, depending on the type
      of immunosuppressive treatment, quantification of TTV or EBV as biomarkers has
      limited potential for defining the net state of immune suppression.

PMID- 29644249
TI  - Schistosomiasis Presenting as Recurring Sigmoid Volvulus in a Danish Man With an
      Inconspicuous Travel History-A Case Report.
AB  - A healthy 72-year-old Danish male presenting with recurring sigmoid volvulus was
      found to be infested with Schistosoma mansoni. No other explanation for recurring
      volvulus was found. A travel history 12 years ago, which included bathing in the
      Botswana Okavango delta for 10 minutes, revealed the likely time and place of
      infection. To our knowledge, this is the first reported case of recurrent sigmoid
      volvulus and chronic intestinal schistosomiasis in a patient from a nonendemic
      area.

PMID- 29644250
TI  - Symptomatic Acute Toxoplasmosis in Returning Travelers.
AB  - We report a family who acquired acute toxoplasmosis after a trip to Central
      America. One member developed severe clinical manifestations including bilateral
      chorioretinitis, hepatitis, and myocarditis requiring therapy. Symptomatic acute
      toxoplasmosis is unusual and possesses a diagnostic challenge. We discuss the
      clinical and epidemiological implications, laboratory diagnosis, and treatment
      plan.

PMID- 29644252
TI  - Strategies for Successful Treatment of Active Tuberculosis in the Setting of
      DRESS on RIPE.
AB  - We describe 2 young, female patients who developed drug reaction with
      eosinophilia and systemic symptoms (DRESS) syndrome while on treatment for
      pulmonary tuberculosis (TB). Active TB was treated successfully with second-line
      TB medications, including moxifloxacin, ethambutol, linezolid, and amikacin for
      18 months.

PMID- 29644251
TI  - Twenty-Year Evolution of Hepatitis B Virus and Human Immunodeficiency Virus
      Prevalence and Incidence in Voluntary Blood Donors in Cote d'Ivoire.
AB  - Background: Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) share
      common risk factors. The parallel description of their frequency over time may
      help capture their similarities and differences. Methods: Using data from the
      National Transfusion Center of Abidjan, we estimated the following over a 20-year
      period: (1) the prevalence of HIV and hepatitis B surface antigen (HBsAg)
      positivity at first contact; and (2) the incidence of HIV and HBsAg
      seroconversion in negative first-time blood donors. Results: Between 1992 and
      2012, 422319 donors (men [M] = 74%) provided 1063825 blood donations. For first
      time donors, HIV prevalence decreased from 7.1% (M = 5.9%, women [W] =11.0%) in
      1992-1994 to 1.1% (M = 0.8%, W = 2.0%) in 2010-2012. Prevalence of HBsAg
      positivity remained stable at 10.8% (M = 11.7%, W = 7.3%) in 1992-1994 to 11.1%
      (M = 12.5%, W = 7.1%) in 2010-2012. Among regular donors (N = 129256), the
      incidence of becoming HIV or HBsAg positive, respectively, decreased from 4.9 per
      100 (M = 4.5, W = 8.6) and 7.3 per 100 person-years (M = 7.8, W = 2.3) in 1992
      1994 to 0.07 (M = 0.06, W = 0.11) and 0.2 per 100 person-years (M = 0.2, W = 0.2)
      in 2010-2012. Conclusions: Human immunodeficiency virus prevalence and incidence
      decreased dramatically over time, whereas HBV prevalence remained stable.
      Incidence of HBsAg seroconversion, although decreasing, still reached unexpected
      levels, suggesting that the risk of HBV infection in adults may be higher than
      expected. Hepatitis B surface antigen-negative blood-donors should be offered HBV
      vaccination.

PMID- 29644253
TI  - Lectin Binding Analysis of Streptococcus mutans Glycoproteins.
AB  - Bacterial glycoproteins are of increasing interest due to their abundance in
      nature and importance in health and infectious diseases. However, only a very
      small fraction of bacterial glycoproteins have been characterized and its post
      translational modification machinery identified. While analysis of glycoproteins
      can be achieved through various techniques, this is often limited by the specific
      characteristics of individual proteins such as type and level of glycosylation.
      Lectins are sugar-binding proteins that recognize specific glycoconjugates in a
      manner similar to antigen-antibody interactions. Here, we describe a simple
      method for the detection of glycoproteins using lectin-based Western blot
      analysis, which can be applied to different organisms and coupled with various
      other strategies for complementary analysis.

PMID- 29644254
TI  - FRET-based Stoichiometry Measurements of Protein Complexes in vitro.
AB  - For a complete understanding of biochemical reactions, information on complex
      stoichiometry is essential. However, measuring stoichiometry is experimentally
      challenging. Our lab has developed a FRET-based assay to study protein complex
      stoichiometry in vitro. This assay, also known as Job plot, is set up as a
      continuous variation of the molar ratio between the two species, kept at constant
      total concentration. The FRET (Fluorescence Resonance Energy Transfer) between
      the two fluorescently-labeled proteins is measured and the stoichiometry is
      inferred from the sample with highest FRET signal. This approach allows us to
      assess complex stoichiometry in solution.

PMID- 29644255
TI  - Conditional Knockdown of Proteins Using Auxin-inducible Degron (AID) Fusions in
      Toxoplasma gondii.
AB  - Toxoplasma gondii is a member of the deadly phylum of protozoan parasites called
      Apicomplexa. As a model apicomplexan, there is a great wealth of information
      regarding T. gondii's 8,000+ protein coding genes including sequence variation,
      expression, and relative contribution to parasite fitness. However, new tools are
      needed to functionally investigate hundreds of putative essential protein coding
      genes. Accordingly, we recently implemented the auxin-inducible degron (AID)
      system for studying essential proteins in T. gondii. Here we provide a step-by
      step protocol for examining protein function in T. gondii using the AID system in
      a tissue culture setting.

PMID- 29644256
TI  - Registration and Alignment Between in vivo Functional and Cytoarchitectonic Maps
      of Mouse Visual Cortex.
AB  - This protocol describes a method for registration of in vivo cortical retinotopic
      map with cytochrome c oxidase (CO) labeled architectonic maps of the same mouse
      brain through the alignment of vascular fiducials. By recording surface blood
      vessel pattern and sequential alignment at each step, this method overcomes the
      challenge imposed by tissue distortion during perfusion, mounting, sectioning and
      histology procedures. This method can also be generalized to register and align
      other types of in vivo functional maps like ocular dominance map and
      spatial/temporal frequency tuning map with various anatomical maps of mouse
      cortex.

PMID- 29644257
TI  - Intravenous Labeling and Analysis of the Content of Thymic Perivascular Spaces.
AB  - Following development in the thymus, T cells are thought to exit into the
      periphery predominantly through perivascular spaces (PVS). This exit route is
      used by conventional T cells, and likely also applies to unconventional T cell
      subsets, such as precursors of CD8alphaalpha and TCRgammadelta intraepithelial
      lymphocytes, regulatory T cells and natural killer T cells. Additional cell types
      might also be found in the PVS and initiate interactions with exiting T cells.
      The exact content of the PVS, and the processes within, are not well studied. To
      distinguish vascular from resident cells within various tissues by flow
      cytometry, intravenous (i.v.) labeling is becoming a commonly employed method. We
      recently used anti-CD45.2 antibodies and magnetic enrichment to further evaluate
      this technique, and compared labeled and unlabeled cells in the thymus and blood.
      This assay can be used to specifically investigate hematopoietic cell subsets
      within the PVS of the thymus.

PMID- 29644258
TI  - CRISPR-mediated Tagging with BirA Allows Proximity Labeling in Toxoplasma gondii.
AB  - Defining protein interaction networks can provide key insights into how protein
      complexes govern complex biological problems. Here we define a method for
      proximity based labeling using permissive biotin ligase to define protein
      networks in the intracellular parasite Toxoplasma gondii. When combined with
      CRISPR/Cas9 based tagging, this method provides a robust approach to defining
      protein networks. This approach detects interaction within intact cells, it is
      applicable to both soluble and insoluble components, including large proteins
      complexes that interact with the cytoskeleton and unique microtubule organizing
      center that comprises the apical complex in apicomplexan parasites.

PMID- 29644259
TI  - RNA Cap Methyltransferase Activity Assay.
AB  - Methyltransferases that methylate the guanine-N7 position of the mRNA 5' cap
      structure are ubiquitous among eukaryotes and commonly encoded by viruses. Here
      we provide a detailed protocol for the biochemical analysis of RNA cap
      methyltransferase activity of biological samples. This assay involves incubation
      of cap-methyltransferase-containing samples with a [32P]G-capped RNA substrate
      and S-adenosylmethionine (SAM) to produce RNAs with N7-methylated caps. The
      extent of cap methylation is then determined by P1 nuclease digestion, thin-layer
      chromatography (TLC), and phosphorimaging. The protocol described here includes
      additional steps for generating the [32P]G-capped RNA substrate and for preparing
      nuclear and cytoplasmic extracts from mammalian cells. This assay is also
      applicable to analyzing the cap methyltransferase activity of other biological
      samples, including recombinant protein preparations and fractions from analytical
      separations and immunoprecipitation/pulldown experiments.

PMID- 29644260
TI  - Biochemical Analysis of Dimethyl Suberimidate-crosslinked Yeast Nucleosomes.
AB  - Nucleosomes are the fundamental unit of eukaryotic chromosome packaging,
      comprised of 147 bp of DNA wrapped around two molecules of each of the core
      histone proteins H2A, H2B, H3, and H4. Nucleosomes are symmetrical, with one axis
      of symmetry centered on the homodimeric interaction between the C-termini of the
      H3 molecules. To explore the functional consequences of nucleosome symmetry, we
      designed an obligate pair of H3 heterodimers, termed H3X and H3Y, allowing us to
      compare cells with single or double H3 alterations. Our biochemical validation of
      the heterodimeric X-Y interaction included intra-nucleosomal H3 crosslinking
      using dimethyl suberimidate (DMS). Here, we provide a detailed protocol for the
      use of DMS to analyze yeast nucleosomes.

PMID- 29644261
TI  - Detection and Analysis of Circular RNAs by RT-PCR.
AB  - Gene expression in eukaryotic cells is tightly regulated at the transcriptional
      and posttranscriptional levels. Posttranscriptional processes, including pre-mRNA
      splicing, mRNA export, mRNA turnover, and mRNA translation, are controlled by RNA
      binding proteins (RBPs) and noncoding (nc)RNAs. The vast family of ncRNAs
      comprises diverse regulatory RNAs, such as microRNAs and long noncoding
      (lnc)RNAs, but also the poorly explored class of circular (circ)RNAs. Although
      first discovered more than three decades ago by electron microscopy, only the
      advent of high-throughput RNA-sequencing (RNA-seq) and the development of
      innovative bioinformatic pipelines have begun to allow the systematic
      identification of circRNAs (Szabo and Salzman, 2016; Panda et al., 2017b; Panda
      et al., 2017c). However, the validation of true circRNAs identified by RNA
      sequencing requires other molecular biology techniques including reverse
      transcription (RT) followed by conventional or quantitative (q) polymerase chain
      reaction (PCR), and Northern blot analysis (Jeck and Sharpless, 2014). RT-qPCR
      analysis of circular RNAs using divergent primers has been widely used for the
      detection, validation, and sometimes quantification of circRNAs (Abdelmohsen et
      al., 2015 and 2017; Panda et al., 2017b). As detailed here, divergent primers
      designed to span the circRNA backsplice junction sequence can specifically
      amplify the circRNAs and not the counterpart linear RNA. In sum, RT-PCR analysis
      using divergent primers allows direct detection and quantification of circRNAs.

PMID- 29644262
TI  - The Stress Acceleration Hypothesis: Effects of early-life adversity on emotion
      circuits and behavior.
AB  - The importance of early experiences for mental health across the lifespan is well
      recognized. In particular, there is a strong association between adverse
      caregiving experiences and mental illness. However, relative to studies assessing
      outcomes in adults, there are far fewer studies assessing the earlier emerging
      manifestations of caregiving adversity during development. This lack of
      developmental research limits an understanding of the mechanisms that link
      adversity with mental illness. Adoption of a developmental approach to research
      in this field will yield greater insights into the factors that tie adversity to
      poor emotion function across a lifespan. In this review, we focus on recent
      findings that have used a developmental approach in the examination of mental
      health and early adversity. These studies are notable in that, across numerous
      species, they converge on the idea that early adversity leads to accelerated
      maturation of emotion circuits in the brain and in the behaviors supported by
      these regions. We propose that these 'stress acceleration' effects are evidence
      of early system adaptation.

PMID- 29644263
TI  - Treatment for unstable pulmonary sequestration injury in patient with severe
      blunt trauma: A case report.
AB  - Case: Pulmonary sequestration is a congenital malformation characterized by
      nonfunctioning tissue not communicating with the tracheobronchial tree. As the
      blood pressure in the artery feeding the sequestrated lung tissue is higher than
      that in the normal pulmonary artery, the risk of massive hemorrhage in pulmonary
      sequestration is high. We herein present the first case of a severe blunt trauma
      patient with unstable pulmonary sequestration injury. Outcome and conclusion: The
      mechanism of pulmonary sequestration injury is vastly different than that of
      injury to normal lung. We suggest that proximal feeding artery embolization
      should be performed before surgical intervention in patients with massive
      hemorrhage of pulmonary sequestration due to severe chest trauma.

PMID- 29644264
TI  - Laparoscopic approach to the management of penetrating traumatic diaphragmatic
      injury.
AB  - Background: Traditionally, laparotomy/thoracotomy is the standard approach for
      thoracoabdominal injuries. However, it has a non-therapeutic rate of 12-40% and
      40% morbidity. Laparoscopy, as a diagnostic and therapeutic modality, has evolved
      to be integral to general and subspecialty surgeons in the management of
      patients. However, its use in the field of trauma surgery has been limited. We
      present a case of traumatic diaphragmatic injury from a low velocity penetrating
      wound successfully repaired through laparoscopic approach. Case presentation: A
      20 year old male, presented with a traumatic diaphragmatic injury secondary to a
      low velocity penetrating injury. A computed tomographic scan revealed a tear on
      the left diaphragm with the superior pole of the spleen and omentum eviscerating
      through. He subsequently underwent diagnostic laparoscopy and primary repair of
      the diaphragmatic injury. His recovery was uneventful and he was discharged on
      the third postoperative day. Conclusion: A review of current literature and our
      case suggest that the use of laparoscopy for the management of penetrating
      thoracoabdominal injuries is continually evolving and has shown to be a promising
      approach compared to traditional laparotomy in carefully selected patients.
      Laparoscopic repair of penetrating traumatic diaphragmatic injuries is a safe and
      expedient option for hemodynamically stable patients.

PMID- 29644265
TI  - Gastric perforation following blunt abdominal trauma.
AB  - Gastric perforations following blunt abdominal trauma are rare, accounting for <
      2% of all blunt abdominal injuries. Isolated blunt gastric ruptures are uncommon.
      They are usually associated with other solid visceral injuries. Injuries to the
      stomach are associated with the highest mortality of all hollow viscus injuries.
      Severity of the injury, timing of presentation and presentation following the
      last meal as well as concomitant injuries are important prognostic factors.
      Imaging modalities may be unreliable in making a diagnosis and thus clinical
      vigilance is mandatory. We present a patient with gastric perforation following
      blunt abdominal trauma and review the literature.

PMID- 29644266
TI  - Ureteric transection secondary to penetrating handlebar injury.
AB  - Ureteric trauma is rare, occurring in < 1% of all traumas. We present a unique
      case of a 13 year old female who sustained a penetrating abdominal injury from a
      bicycle handlebar. Upon initial examination there was herniation of bowel through
      the abdominal wound, so exploratory laparotomy was performed. A serosal injury of
      the colon and bleeding mesenteric veins were encountered; the retroperitoneum was
      not explored at that time. Postoperative course was remarkable for a doubling of
      the serum creatinine, increasing abdominal distention and pain. Computed
      tomography on postoperative day five demonstrated a large amount of intra
      abdominal fluid. The patient was taken for re-exploration. The left ureter was
      found to be completely transected. It was repaired over a double-J stent. This
      case demonstrates the need for a high index of suspicion in the diagnosis of
      ureteric injury.

PMID- 29644267
TI  - Double-plate fixation in double clavicle fractures: A case report.
AB  - Bilateral clavicle fractures are rare; Double clavicle fractures are particularly
      rare. We report a case of a 23-year-old woman presenting with double fractures
      (middle and distal end) of the right clavicle and single fracture of the left
      clavicle after she suffered a road traffic accident. Four days after the injury,
      the right clavicle was fixed with a reconstruction locking plate and a hook
      plate, the left clavicle was fixed by a S-shaped locking plate. Bone union was
      achieved 3 months after surgery. The patient regained full range of shoulder
      motion with a mild pain in the right acromion 21 months after the operation. To
      our knowledge, treating double clavicle fractures using double-plate fixation has
      not been described. Our case shows that double-plate fixation was successful in
      achieving an excellent long-term outcome.

PMID- 29644268
TI  - Well leg compartment syndrome.
AB  - Well leg compartment syndrome refers to the occurrence of compartment syndrome in
      an uninjured limb in the absence of an underlying systemic predisposing cause. It
      is a rare phenomenon with devastating clinical consequences resulting from
      commonly utilized operative positions and requires a high index of suspicion for
      diagnoses. There are only a few reports in the literature and a lack of awareness
      of the condition. Identifying patients with at risk predisposition and increasing
      surveillance in these patients may allow for early detection and decrease the
      morbidity and potential mortality associated with well-leg compartment syndrome.

PMID- 29644269
TI  - Blunt traumatic celiac artery avulsion managed with celiac artery ligation and
      open aorto-celiac bypass.
AB  - Traumatic celiac artery injuries are rare and highly lethal with reported
      mortality rates of 38-62%. The vast majority are caused by penetrating trauma
      with only 11 reported cases due to blunt trauma (Graham et al., 1978; Asensio et
      al., 2000, 2002). Only 3 of these cases were complete celiac artery avulsions.
      Management options described depend upon the type of injury and have included
      medical therapy with anti-platelet agents or anti-coagulants, endovascular
      stenting, and open ligation. We report a case of a survivor of complete celiac
      artery avulsion from blunt trauma managed by open bypass.

PMID- 29644270
TI  - Importance of the capability for complete resuscitative treatment combining
      surgery and interventional radiology for potentially lethal multiple injuries: A
      case report.
AB  - Background: Recently, trauma management has been complicated owing to the
      introduction of damage-control strategies and interventional radiology. Here, we
      discuss important aspects regarding survival of patients with severe trauma. Case
      presentation: A 74-year-old Japanese woman experienced a traffic accident on a
      highway. On arrival, paramedics were unable to measure her blood pressure, and
      her condition deteriorated. The patient was immediately transferred to our
      hospital in a physician-staffed emergency helicopter, during which she was
      administered emergency blood transfusions. On admission, her systolic blood
      pressure was 44 mmHg, and focused assessment with sonography for trauma yielded
      positive findings at the anterior mediastinum, right thoracic cavity, and intra
      abdominal cavity. Plain radiography revealed a partial unstable-type pelvic
      fracture. Immediately, cardiac tamponade caused by the massive anterior
      mediastinal hematoma with internal thoracic vessel injuries was diagnosed through
      a median sternotomy, while a diaphragmatic rupture and hemorrhage from the intra
      abdominal cavity were diagnosed through right anterior-lateral thoracotomy.
      Furthermore, massive bowel and mesenteric vessel injuries were diagnosed through
      laparotomy; all of these injuries were treated sequentially as a simplified
      process. The patient then underwent transcatheter arterial embolization for the
      retroperitoneal hematoma and the pelvic fracture. Reestablishing intestinal
      continuity was performed after intensive care. All procedures were seamlessly
      performed by trained emergency physicians, and the postoperative course was
      uneventful, with the patient recovering completely after rehabilitation.
      Conclusions: The capability to perform complete resuscitative treatments that
      seamlessly combine surgery and interventional radiology in the appropriate order
      is important for the survival of patients with multiple traumatic injuries.

PMID- 29644271
TI  - Venlafaxine-induced REM sleep behavioral disorder presenting as two fractures.
AB  - Rapid eye movement (REM) sleep behavioral disorder is characterized by the
      absence of muscular atonia during REM sleep. In this disorder, patients can
      violently act out their dreams, placing them at risk for traumatic fractures
      during these episodes. REM sleep behavioral disorder (RBD) can be a sign of
      future neurodegenerative disease and has also been found to be a side effect of
      certain psychiatric medications. We present a case of venlafaxine-induced RBD in
      a 55 year old female who presented with a 13 year history of intermittent
      parasomnia and dream enactment in addition to a recent history of two fractures
      requiring intervention.

PMID- 29644272
TI  - Bilateral perforating eye injury with metallic foreign bodies caused by tire
      explosion: Case report.

PMID- 29644273
TI  - Emergency department repair of blunt right atrial rupture utilizing
      cardiopulmonary bypass.
AB  - Blunt cardiac injury (BCI) with free wall rupture carries a high risk of pre
      hospital death. Cardiopulmonary bypass (CPB) has been utilized as a bridge to
      repair of cardiac lesions in select patients. We present an interesting case of
      emergency department repair of right atrial rupture with cardiopulmonary bypass.

PMID- 29644274
TI  - Ocular manifestations of TASER-induced trauma.
AB  - A young adult male experienced penetrating globe injury due to a Thomas A. Swift
      Electric Rifle (TASER). Despite successful repair of the globe, the damage was
      profound. This case report explores the complex ways in which mechanical and
      electrical forces from a TASER may impact the structural integrity and the
      neurosensory structures of the eye.

PMID- 29644275
TI  - Delayed identification of an isolated paediatric capitate fracture.
AB  - Fractures of the capitate bone are the second most common injury to a child's
      wrist but are rarely encountered in isolation. This is reflected in the paucity
      of described cases in the literature. Their true incidence is unknown as they
      often do not appear on plain radiographs and may heal without immobilisation. The
      easiest way to detect these fractures is with an MRI scan. The authors present a
      rare case of isolated capitate fracture that was initially missed on plain films.
      This case is important as it highlights the need for a high index of suspicion in
      paediatric patients with unresolving wrist pain.

PMID- 29644276
TI  - Symptomatic sacrococcygeal joint dislocation treated using closed manual
      reduction: A case report with 36-month follow-up and review of literature.
AB  - Dislocation of the sacrococcygeal joint is a rare injury from trauma to the
      buttocks, most often from falling backwards. Standard of care for this injury has
      not been determined because it is rare. Left untreated this can cause coccydynia
      in the long-term. Here we present a case report to describe the treatment of an
      anterior sacrococcygeal dislocation with closed manual reduction. A 13-year-old
      female presented to the emergency department with buttock pain after slipping
      backwards down the stairs. On X-ray the coccyx was in bayonette apposition to the
      anterior distal sacrum and shortened by 6 mm. To manage the injury, closed manual
      reduction of the sacrococcygeal joint was performed. To our knowledge, this is
      the first successful case of sacrococcygeal dislocation treated with closed
      manual reduction, resulting in complete relief of symptoms at 36 months follow
      up. Sacrococcygeal dislocations can be treated with closed manual reduction,
      resulting in lower morbidity and faster recovery compared to surgical treatment.

PMID- 29644277
TI  - Isolated orbital roof blow-in fracture.
AB  - We report a rare case of a right orbital roof blow-in fracture in a 40-year-old
      male with concomitant basal skull fracture and intracranial hemorrhage after a
      fall backward. Trauma, neurosurgery, ophthalmology, and maxillofacial surgery
      consultations were obtained. Conservative, non-surgical management was
      recommended for all injuries, and outpatient follow up for orbital fracture with
      no surgery offered.

PMID- 29644278
TI  - Fabella fracture with radiological imaging: A case report.
AB  - The fabella is a kind of sesamoid bone which is located in the lateral head of
      the gastrocnemius muscle. A slice of studies demonstrated that fabella is
      involved in the knee joint stabilization. Fabella fracture may cause knee pain or
      functional impairment as the previous reports pointed. It is extremely rare,
      which leads to its high rate of missed diagnosis in clinical and radiography to
      some extent. We report a case of a 38-year-old female who was struck by an
      electromobile. The fabella fracture was confirmed on X-ray plain films. After
      that, the degree of injury was evaluated with the magnetic resonance imaging
      (MRI).

PMID- 29644279
TI  - Blunt innominate artery trauma requiring repair and carotid ligation.
AB  - Traumatic dissection of the innominate artery is a rare clinical entity.
      Management of a patient with motorsensory compromise and dissection extending to
      the subclavian and right common carotid arteries is quite rare and can be quite
      involved. Here we present such a case and discuss the unique peri-operative
      decision-making in the context of what is reported in the literature. Restoration
      of motorsensory function is critical and in this case, requiring a multi
      disciplinary team.

PMID- 29644280
TI  - Atypical cardioversion in unstable arrhythmia caused by clavicle surgery.
AB  - We report on a 54-year old male with traumatic brain injury, flail chest and
      floating shoulder undergoing intramedullary stabilization of a midshaft clavicle
      fracture in beach chair position. Intraoperatively the patient developed instable
      atrial fibrillation triggered by implantation of intramedullary nail. Secondary
      this case shows feasibility of cardioversion in latero-lateral electrode-position
      due to inaccessible standard positions and patient fixation between the operation
      table and the X-ray apparatus.

PMID- 29644281
TI  - Thyrohyoid membrane transection caused by a stab injury.
AB  - Background: The thyrohyoid membrane is located between the hyoid bone and thyroid
      cartilage. Transection of the thyrohyoid membrane can be fatal. Case
      presentation: A 54-year-old man presented to the emergency room after attempting
      to commit suicide by cutting his neck. An endotracheal tube was inserted through
      the thyrohyoid membrane, which had been cut almost completely. After a
      tracheostomy, temporary wound closure was performed due to coagulopathy caused by
      hemorrhagic shock. Several hours later, a hyoidothyroidopexy was performed.
      Damage control surgery was applied to this patient's neck injury. The
      tracheostomy tube was removed postoperatively and he was discharged without
      complications. Conclusion: Damage control surgery could be an option for airway
      injury with blood clotting problems due to massive bleeding after securing a
      patent airway.

PMID- 29644282
TI  - Teriparatide and vertebral fracture healing in Ankylosing Spondylitis.
AB  - Patients with Ankylosing Spondylitis (AS) are four times more likely to sustain
      spinal fractures. Due to the associated risk of neurological complications
      treatment is complex. We present the case of a 56-year-old Caucasian gentleman
      with AS who sustained a fracture of T2 vertebra following a traumatic
      hyperextension injury. He declined surgery in fear of complications and started
      treatment with subcutaneous Teriparatide at a dose of 20 mg daily for six months.
      There was complete healing of the vertebral fracture at 6 months without any
      complications. This case is unique as complete healing was achieved without
      preceding surgical intervention. Further exploration of the use of Teriparatide
      in spinal fractures in patients with AS is recommended to support the theories
      generated by this and other existing cases in the literature.

PMID- 29644283
TI  - Plating of an isolated fracture of shaft of ulna under local anaesthesia and
      periosteal nerve block.
AB  - Isolated fractures of shaft of ulna are common. Plate fixation with anatomic
      reduction is thought to produce the best functional results in closed or open
      fractures. Surgery can be done under general and various types of regional
      anaesthesia. We report a case of fracture shaft of ulna treated by plating under
      a combination of WALANT (wide awake, local anaesthesia, no tourniquet) using
      tumescent anaesthesia and periosteal nerve block as a day care procedure.

PMID- 29644284
TI  - Primary repair of a delayed presentation thoracic oesophageal gunshot injury: A
      report of two cases.
AB  - Thoracic oesophageal gunshot injuries are uncommon, and the morbidity and
      mortality rates are extremely high and depend on the elapsed time, injury
      severity, and concomitant organ damage. Thus, early diagnosis is paramount to
      avoid delays, which in turn confer poorer outcomes. Current management strategies
      are still controversial and depend on the patient's physiologic state. We
      experienced two cases of thoracic oesophageal gunshot injury, both of whom were
      treated by primary repair and were successfully discharged. Decision-making
      strategies should be based on the patient's physiologic reserve, experience of
      the attending surgical team, and ancillary services available at the facility.

PMID- 29644285
TI  - Initial experience with the treatment of concomitant aortic pseudoaneurysm and
      thoracolumbar spinal fracture: Case report.
AB  - One blunt abdominal aortic disruption (BAAD) and one blunt thoracic aortic injury
      (BTAI) case are presented. Both aortic injuries were combined with spinal
      fractures. In the BAAD case the aortic pseudoaneurysm manifested just above the
      lumbar fracture while in the BTAI case the aortic injury appeared several
      vertebras below the thoracal fracture site, suggesting different mechanisms in
      the aortic wall damage. In both cases the aortic wall first was sealed,
      successfully, by endovascularly-placed stents, meaning the risks of open aortic
      reconstructive surgery could be avoided. The adjacent crucial vessel's
      preservation, despite the stent covering the left subclavian artery and the left
      common carotid artery in one of the cases was verified by post-operative computed
      tomography angiography (CTA) examination. In second stage those spinal fractures
      which were deemed unstable were stabilized by the fixateur interne (a
      transpedicular screw-rod system). With this treatment sequence we wanted to avoid
      the unnecessary risk of a possible rupture of the unsealed aortic wall during
      positioning for the spinal procedure and during the spinal surgery. Both patients
      recovered from their aortic and spinal injuries.

PMID- 29644286
TI  - Jahss type one posterior first metatarsophalangeal dislocation treated with open
      reduction without fixation: A case report.

PMID- 29644287
TI  - Successful use of intrapelvic Quikclot in life-threatening blast injury.
AB  - Patients that suffer multiple traumatic injuries often present with
      uncontrollable haemorrhage and rapidly descend into a viscous death triad
      consisting of hypothermia, coagulopathy and acidosis. Initial surgical
      intervention does not aim to provide conclusive repair, but instead strives to
      stop blood loss while priority is given to correct the patient's metabolic state
      (Duchesne et al., 2010). However in some cases of massive polytrauma, gaining
      surgical control of bleeding can be incredibly difficult. As a result a number of
      topical haemostatic agents were developed for use in military and civilian
      settings. This case details a successful intracavity use of the granular
      haemostatic agent, QuikclotTM (Z-Medica), in halting massive haemorrhage in a
      patient who sustained major blast injuries. Although not officially recommended,
      intracorporeal uses of QuikclotTM can be effective as a last resort in preventing
      loss of life in cases of severe polytrauma. However, users need to remain wary of
      complications which may arise due to its application.

PMID- 29644288
TI  - Massive bilateral chylothorax post blunt trauma.
AB  - Chylothorax caused by blunt trauma is extremely rare. We present a case of
      bilateral massive chylothorax post blunt trauma and a review of the literature
      regarding the identification and management of this rare diagnosis. An eighteen
      year-old male was involved in a motor vehicle crash where he sustained multiple
      injuries including a right, moderate to large, haemopneumothorax, a small left
      haemopneumothorax, left T8, T9, L1 and L2 acute transverse process fractures and
      fractures of bilateral 11th ribs. An intercostal catheter was inserted on the
      right side which initially drained blood-stained fluid however milky colour fluid
      was noted to be draining 11 h post insertion. Further imaging revealed a left
      pleural effusion causing a mediastinal shift where, once drained, also revealed a
      chylothorax. The patient was managed conservatively with bilateral intercostal
      catheters and a no fat/low-fat diet. The patient was discharged day seven post
      removal of bilateral intercostal catheters.

PMID- 29644289
TI  - Transpedicular direct osteosynthesis of hangman's fracture from a mini-open
      exposure as a less invasive procedure: A technical note.
AB  - This surgical technical case report presents initial clinical experience and
      preliminary results with a less invasive surgical solution for selected hangman's
      fracture. A well-known stabilization technique (i.e. direct transpedicular
      osteosynthesis) was applied through a minimally invasive small incision
      transmuscular posterior approach guided by a standard C-arm fluoroscopy. This
      mini-open approach to C2 vertebra allows similar dissection, visualization of the
      bony landmarks, visual control of the transpedicular screw path drilling, tapping
      and screw insertion to the standard posterior cervical spine approach. At the
      same time it has the benefits of less invasive procedures.

PMID- 29644290
TI  - Posterior dislocation of a native hip joint associated with ipsilateral per
      trochanteric fracture: A rare case report.
AB  - We describe a case of traumatic posterior dislocation of a native hip joint
      associated with ipsilateral comminuted inter-trochanteric femoral fracture. In
      our case, closed reduction was attempted but proved unsuccessful. Taking into
      account the planned subsequent intra-medullary femoral nail, open reduction
      through a lateral incision was undertaken. Post-operatively, the planned mobility
      was for a non-weight bearing period of 6 weeks followed by a partial-weight
      bearing period of 6 weeks before progressing to full-weight bearing. Post
      operatively, the patient completed a comprehensive course of physiotherapy. At
      five months, he was able to walk for five miles over the course of a weekend. At
      six months, the patient was looking at phased return to work as a fire fighter.
      Radiographs taken at the time demonstrated evidence of healing to his inter
      trochanteric fracture. At ten months, the patient was back to normal duties at
      work as a fire fighter.

PMID- 29644291
TI  - Profunda femoris artery injury caused by lesser trochanter fragment in
      intertrochanteric fracture: A case report.
AB  - Vascular injuries following intertrochanteric fracture have been sporadically
      reported. Despite its rare occurrence, this complication can be potentially life
      and limb threatening. The authors report an unusual presentation of false
      aneurysm of profunda femoris artery following an intertrochanteric fracture with
      marked displacement of lesser trochanter fragment. The patient presented with
      thigh swelling and unexplainable dropped hematocrit. Surgical exploration and
      vascular repair were done. It is essential for the surgeon to be aware of
      possible associated vascular injuries in intertrochanteric fracture, particularly
      in fracture with lesser trochanter fragment.

PMID- 29644292
TI  - Serious phlegmonous lesion of the hand following an injury by vegetal thorn:
      Never forget Pasteurella multocida!
AB  - Pasteurella multocida can cause serious infections after dog or cat bite. We
      report here a rare case of hand infection caused by P. multocida consecutive to
      an injury by a thorn of the prickly pear. It caused an amputation of the distal
      phalanx of the thumb in a trisomic patient. It is about a 27-year-old man who was
      admitted to the hospital with swelling and intense pain of the left hand. He
      reported a sting by a thorn of prickly pear 15 days before. The patient was
      admitted to proceed with operative irrigation and debridement. The pus was
      collected for microbiological examination. Microscopic examination after Gram
      staining revealed small Gram-negative coccobacilli, associated to
      polymorphonuclear reaction. Culture have objectivated Pasteurella multocida. The
      isolated strain was susceptible to betalactamins. Patient was treated with
      ampicillin. Well-conducted antibiotics and repetitive local cares have not
      prevented local lesions from progressing to necrosis of the soft parts of the
      thumb and osteitis of the distal phalanx of the thumb. The patient underwent a
      necrosectomy and an amputation of the distal phalanx. Ampicillin was replaced by
      amoxicillin/clavulanic acid and after 15 days, progression was clinically and
      microbiologically favorable. In the case we report, since the patient does not
      report any exposure or contact with animals, the thorn prick is the source of
      infection. It was contaminated from the animal reservoir. Taking into account the
      monomicrobism of the infection, treatment with aminopenicillins was sufficient.
      Our propositus came to the hospital 15 days after the inoculation of the
      bacterium. This duration appears to be very late in relation to the acute
      character of pasteurellosis. This was probably the main reason why the local
      infection evolved towards osteoarticular complications. That's why, we should
      consider Pasteurella multocida in case of infection by inoculation, even in the
      absence of contact with the animals.

PMID- 29644293
TI  - Luxatio erecta with greater tuberosity fracture: A case report.
AB  - Luxatio erecta is an unusual humeral dislocation. It is frequently associated
      with neurovascular injuries and concomitant fracture. As such, they require a
      thorough clinical and imaging evaluation. The vast majority of cases may be
      treated with closed reduction alone, but infrequently, some may require an open
      procedure. The authors report a case of luxatio erecta with fracture of greater
      tuberosity to underline the rarity of this entity, and to describe the mechanism
      of this injury and the therapeutic modalities.

PMID- 29644294
TI  - Isolated right atrial appendage rupture following blunt chest trauma.
AB  - Background: Right sided tears or rupture are the most common injury to the heart
      after blunt chest trauma. The majority of these injuries are to the thin walled
      atrium. Reports of localized right atrial appendage rupture are rare. The
      classical features of Beck's triad are unreliable in the trauma bay. With the
      advent of EFAST (Focused assessment with sonography for trauma extended to
      thorax), Beck's triad should be considered but not used as the primary clinical
      tool for diagnosis of cardiac tamponade [1]. EFAST aids in rapid diagnosis and
      definitive care [3]. Case presentation: Our patient was a 17 year old male who
      presented with hypotension after a rollover motor vehicle accident. He presented
      with a grossly negative physical exam and positive EFAST for pericardial effusion
      with tamponade physiology. We performed an emergency pericardiocentesis and
      expedited transportation for operative exploration. A Right atrial appendage
      injury was identified and repaired and patient recovered uneventfully.
      Conclusion: EFAST examination aids in rapid diagnosis of cardiac tamponade in the
      trauma setting. Pericardiocentesis facilitates temporizing the hemodynamics in
      preparation for operative exploration.

PMID- 29644295
TI  - Successful management of suicidal cut throat injury with internal jugular,
      tracheal and esophageal transection: A case report.

PMID- 29644296
TI  - Bilateral posterior fracture-dislocation of the shoulder after epileptic seizure.
AB  - We present a case of a 61 year-old woman who suffered a bilateral posterior
      fracture-dislocation of the shoulder after an isolated episode of epileptic
      seizure. The patient was diagnosed at our Emergency department with x-rays and CT
      scans after being found unconscious. An indication for bilateral shoulder
      hemiprosthesis implant was initially given. However, given the peculiar pattern
      of the fracture, the hemiprosthesis was implanted on one side only, while the
      other side was treated with ORIF with four cannulated screws. After the one year,
      the patient had resumed her previous activities and had no complaints. We
      performed a review of similar cases in literature and provided a rationale for
      our choice of treatment and the reasons for its success.

PMID- 29644297
TI  - Negative-pressure in treatment of persistent post-traumatic subcutaneous
      emphysema with respiratory failure: Case report and literature review.
AB  - Subcutaneous emphysema may aggravate traumatic pneumothorax treatment, especially
      when mechanical ventilation is required. Expectative management usually suffices,
      but when respiratory function is impaired surgical treatment might be indicated.
      Historically relevant methods are blowhole incisions and placement of various
      drains, often with related wound complications. Since the first report of
      negative pressure wound therapy for the treatment of severe subcutaneous
      emphysema in 2009, only few publications on use of commercially available sets
      were published. We report on patient injured in a motor vehicle accident who had
      serial rib fractures and bilateral pneumothorax managed initially in another
      hospital. Due to respiratory deterioration, haemodynamic instability and renal
      failure patient was transferred to our Intensive Care Unit. Massive and
      persistent subcutaneous emphysema despite adequate thoracic drainage with
      respiratory deterioration and potentially injurious mechanical ventilation with
      high airway pressures was the indication for active surgical treatment. Negative
      pressure wound therapy dressing was applied on typical blowhole incisions which
      resulted in swift emphysema regression and respiratory improvement. Negative
      pressure wound therapy for decompression of severe subcutaneous emphysema
      represents simple, effective and relatively unknown technique that deserves wider
      attention.

PMID- 29644298
TI  - Use of Idarucizumab for dabigatran reversal: Emergency department experience in
      two cases with subdural haematoma.
AB  - Introduction: Idarucizumab is the first effective humanized monoclonal antibody
      fragment developed specifically as a reversal agent for dabigatran, a Direct Oral
      Anticoagulant. Despite recent trials demonstrating reversal of clinically
      relevant bleeding, there is a paucity of data on use outside the trial setting.
      This manuscript describes the use of Idarucizumab to reverse dabigatran in two
      patients presenting to the emergency department of a major tertiary hospital with
      acute traumatic subdural haematomas (SDH). Methods: Patients were identified
      through retrospective review of medication dispensing systems and electronic
      medical records. Results: Two cases of Idarucizumab use were identified. Case 1
      was of a 63-year-old male who presented following a motorcycle crash. Case 2 was
      of a 77-year-old male who presented with a 3-week history of ataxia and recurrent
      falls. Both patients were taking dabigatran for atrial fibrillation (AF). CT
      Brain revealed acute SDH with clinical indications for urgent surgical
      evacuation. Serum dabigatran levels were obtained on arrival in the emergency
      department with levels of 155 ng/ml and 110 ng/ml (reference range 117-275
      ng/ml). Idarucizumab for dabigatran reversal was commenced; Case 1 received 5 g
      Idarucizumab as an intravenous bolus dose, while Case 2 received 5 g Idarucizumab
      as two 2.5 g intravenous infusions. Serum dabigatran levels for Cases 1 and 2
      were 0 ng/ml at 75 min and 340 min post Idarucizumab administration respectively.
      Both patients proceeded to craniotomy with evacuation of the SDH. There was no
      extension of the SDH in either case. Anticoagulation was withheld until
      outpatient clinic review, and both patients transferred for rehabilitation prior
      to discharge home. Conclusion: Idarucizumab was clinically effective for
      reversing dabigatran, resulting in undetectable serum levels, and should be
      considered in patients presenting to hospital with clinically significant
      bleeding associated with dabigatran therapy.

PMID- 29644299
TI  - Surgical management of compartment syndrome and the gradual closure of a
      fasciotomy wound using a DermaClose device.
AB  - The immediate recognition and timely response of compartment syndrome due to
      damage caused by penetrating trauma has immense clinical outcomes. The following
      is a case report of a complicated fasciotomy in a 33-year-old male who suffered a
      gunshot wound to his left lower extremity and the surgical management leading to
      adequate limb salvage and recovery.

PMID- 29644300
TI  - A rare case of a superior lumbar hernia secondary to penetrating injury.
AB  - Lumbar hernias are rare occurrences, with only 300 cases reported in the
      literature. We present a unique case of a superior lumbar hernia secondary to
      penetrating trauma to the right flank. We performed a herniorrhaphy using porcine
      mesh, and provided additional support by mobilizing the external oblique and
      latissimus dorsi into the defect. At follow up three months after repair, the
      patient was asymptomatic and exam revealed an intact lumbar abdominal wall with
      normal contour. Although literature displays a consensus on the need for lumbar
      hernia repair, specific repair techniques must be tailored to defect etiology,
      size, location, and contents.

PMID- 29644301
TI  - Pseudoaneurysm of brachial artery: A rare cause of median nerve compression.
AB  - Background: The authors present an unusual clinical case of high median nerve
      compression caused by an iatrogenic pseudoaneurysm of the brachial artery after
      an angiography with a follow up of 9 months. Methods: A 73-year-old male was seen
      with progressive numbness, loss of opponency and diminution of strength of finger
      flexion in the left hand after an angiography with direct puncture of the left
      humeral artery. Physical examination revealed a hard consistency internal distal
      arm swelling with the size of a walnut, non-pulsatile and with a Tinel sign on
      percussion. Upper extremity arterial Doppler ultrasonography and magnetic
      resonance imaging didn't point to a pseudoaneurysm. Given the persistence and
      progressive worsening of symptoms, the patient was operated at 4 months after the
      beginning of symptoms through an anterior approach of the left elbow. The
      tumefaction corresponded to a brachial artery pseudoaneurysm completely
      thrombosed causing severe compression of the median nerve. Microsurgical
      neurolysis of the median nerve was performed and the pseudoaneurysm was removed.
      Results: At 9 months of follow-up the patient had total recovery of flexion of
      the thumb and forefinger and recovery of opposition with slight hypoesthesia on
      the volar surface of the radial fingers of the hand. Conclusions: This case
      represents a rare form of high median nerve compression after angiography. The
      increased use of endovascular procedures may cause a higher frequency of these
      neurological injuries, and if confirmed, the patient should be operated as soon
      as possible to avoid serious neurological sequelae.

PMID- 29644302
TI  - Perforating head injury with iron rod and its miraculous escape: Case report and
      review of literature.
AB  - Civilian perforating head injury is rare. Because rarity of this injury, there is
      no standard management protocol. We report a case of perforating head injury with
      iron rod, review the literature on the subject and discuss the challenges in the
      management of such case. We have not found similar case in the literature.
      Civilian perforating head injury is rare. A 25-year-male brought to the emergency
      department with approximately two feet perforating iron rod in the head, entering
      via frontal region, left side of midline and coming out of the occipital region.
      He developed right sided hemiplegia and global aphasia. He underwent series of
      imaging for the evaluation of the course of the iron rod and injury sustained
      because of it. Under strict aseptic precaution, iron rod removed in the operation
      theater. His clinical condition improved over a period of three weeks. At one
      year follow up- he had almost normal speech and language functions and was able
      to walk without support. This case illustrates the possibility of bizarre type of
      such injury in the presence of protective helmet and challenges in the
      management. Preoperative planning on the basis of images, prophylactic
      antibiotics and anticonvulsant medications, cleaning of the objects with
      antiseptic solutions, anterograde extraction after adequate exposure around entry
      and exit points resulted in good clinical outcome after successful removal of the
      rod.

PMID- 29644303
TI  - Hoffa's fracture of the medial femoral condyle in a child treated with open
      reduction and internal fixation: A case report.
AB  - Background: Hoffa's fracture is a coronal oriented fracture of the femoral
      condyles. Isolated coronal fracture of medial femoral condyle with intact lateral
      femoral condyle is extremely rare in the pediatric patients. There are only few
      cases of a medial femoral condyle Hoffa's fracture in a skeletally immature
      patient that have been reported in the literature. The Case: In this case report;
      we present a case of a 12-year-old boy with Hoffa's fracture of the medial
      femoral condyle, successfully managed by open reduction and internal fixation.
      Conclusion: Pediatric Hoffa's fractures are very rare and can be missed.
      Treatment should be with open reduction and internal fixation to prevent further
      complications in the long term.

PMID- 29644304
TI  - Trans-triquetral Perilunate fracture dislocation.
AB  - Perilunate dislocations and perilunate fracture dislocations are rare and serious
      injuries. Perilunate dislocations represent less than 10% of all carpal injuries
      of which 61% represent transcaphoid fractures. Because of their rarity, up to 25%
      of perilunate dislocations are initially missed on first assessment. We present
      the case of a 66-year-old-gentleman who sustained an isolated trans-triquetral
      perilunate fracture dislocation while walking his dog. This was diagnosed in the
      emergency department and he underwent open reduction internal fixation after
      failed attempts at closed reduction in the ED and in theatre under general
      anaesthesia. After further removal of his Kirschner wires and physiotherapy he is
      noted to have had a successful outcome with his treatment at 9 months follow up
      post operatively. We found that this is the first case of it's kind reported in
      the literature highlighting the rarity of this injury pattern.

PMID- 29644305
TI  - Horner's syndrome in traumatic first rib fracture without carotid injury; review
      of anatomy and pathophysiology.
AB  - Case report of a 51 year old man involved in a motor vehicle accident presenting
      with multiple thoracic wall injury, including bilateral first rib fractures. He
      slowly developed a right sided Horner's syndrome due to a right paravertebral
      haematoma. The initial imaging did not display any carotid injury, however the
      developing right paravertebral haematoma was not initially reported. We review
      the anatomy and pathophysiology of this well-known but rare condition to show how
      first rib fractures should raise suspicion of Horner's syndrome irrespective of
      the presence or absence of any underlying blunt carotid injury.

PMID- 29644306
TI  - Axillary artery injury after an anterior shoulder fracture dislocation and
      "periosteal sleeve avulsion of the rotator cuff" (SARC). Case report and review
      of the literature.
AB  - We present the rare complication of an axillary artery injury associated with an
      anterior dislocation of the humerus and what we believe to be the first reported
      periosteal sleeve avulsion of the entire rotator cuff (SARC). We review the
      literature and discuss the cause of this unusual injury pattern.

PMID- 29644307
TI  - Bioabsorbable metal screws in traumatology: A promising innovation.
AB  - MAGNEZIX(r) CS (Syntellix AG, Hanover, Germany) is a bioabsorbable compression
      screw made of a magnesium alloy (MgYREZr). Currently there are only two clinical
      studies reporting on a limited number of elective patients who received this
      screw in a hallux valgus operation. We applied MAGNEZIX(r) CS for fixation of
      distal fibular fracture in a trauma patient who had sustained a bimalleolar
      fracture type AO 44-B2.3. Clinical course was uneventful, fracture healing
      occurred within three months. Follow-up X-rays showed a radiolucent area around
      the implant for some months, yet this radiolucent area had disappeared in the 17
      months follow-up X-ray.

PMID- 29644308
TI  - Neurovascular complications after supracondylar humerus fractures in children.
AB  - Background: Supracondylar fractures of the humerus are a common injury in
      pediatric traumatology. The most common operative therapy is closed reduction and
      percutaneous pinning using K-wires. Common complications associated with this
      entity are neurovascular lesions, especially of the brachial artery and the
      median nerve. Methods: We report two cases of patients treated in our trauma
      center with supracondylar fracture of the humerus (AO IV degrees ) and
      neurovascular complications. Results: Both patients underwent open revision and
      recovered completely in their further course. Conclusion: We recommend detailed
      neurovascular examination initially and after reposition of the fracture. The
      threshold for open reduction in cases of irreducible fractures should be low. In
      the presence of neurovascular impairment an open revision is mandatory, even
      months after the initial Trauma.Level of evidence: Level V (case report).

PMID- 29644309
TI  - Open ankle dislocation without associated malleolar fracture: Review of the
      literature.
AB  - Open ankle dislocation without an associated fracture is an extremely rare injury
      [1]. We present a case of a 17-years old male who sustained a serious injury of
      his right ankle during jumping downstairs. He twisted his ankle and sustained an
      open posteromedial dislocation of his right ankle, without an associated
      malleolar fracture. The treatment consisted of wound debridement and irrigation
      open relocation with repair of anterior talo-fibular ligament, and primary
      closure of the skin post operatively the limb was immobilised in short leg cast
      for six weeks in a neutral position allowing partial weight bearing. At the 3
      month follow-up visit, the patient reported that both ankle and feet had regained
      full, pain-free range of motion and he returned to full activity.

PMID- 29644310
TI  - Literature review and case report: Current concepts for concomitant intra and
      extracapsular fractures of neck of femur in elderly patients.
AB  - Though the incidence of concomitant ipsilateral intracapsular and extracapsular
      fracture neck of femur is still a rare presentation in day to day fracture hip
      admissions. Cases of simultaneous ipsilateral intra- and extra-capsular neck of
      femur fractures are forestalled with problems relating to diagnosing this injury
      as well as debate regarding optimal methods of fixation versus arthroplasty. We
      did a literature review to assess frequency of such fracture incidence, highlight
      methods of treatment applied, current practice for management as well as case
      report presentation.

PMID- 29644311
TI  - Transection of the anterior tibial artery during minimally invasive plate
      osteosynthesis of the proximal tibia.
AB  - : Minimally invasive plate osteosynthesis (MIPO) techniques have been developed
      to protect the blood flow to tissues surrounding fractures and reduce the risk of
      non-union. Typically, MIPO involves the insertion of a plate through a small
      incision and fixation with percutaneously applied screws targeted
      fluoroscopically. Here we present a case of a transected anterior tibial artery
      during routine minimally invasive plate osteosynthesis of a tibial plateau
      fracture to highlight a rare complication of this type of surgery and discuss
      relevant anatomical considerations. Level of evidence: According to the OCEBM
      Levels of Evidence Working Group, this study is graded as a Level of Evidence IV.

PMID- 29644312
TI  - Femoral neck pseudoarthrosis in a polio patient treated with closed reduction and
      cell therapy.
AB  - Poliomyelitis disease affects the anterior horns cells of the spinal cord and
      certain motor nuclei of the brain stem. Paralysis type is flaccid and
      asymmetrical and result in muscular imbalance. Due to this, in case of having a
      hip muscles involvement, degenerative or posttraumatic, total hip arthroplasty is
      normally contraindicated because of the excessive risk of hip dislocation. In
      cases of subcapital femoral neck fractures the femoral head vascularization is a
      main concern, and in cases of neglected fracture with pseudoarthrosis the
      vascular status to the head must be investigated prior to further decisions. We
      report the case of a femoral neck fracture non-union after a missed femoral neck
      fracture in a polio affected leg treated with cannulated screws and percutaneous
      autologous injection of processed total nuclear cells (TNC) mixed with putty
      demineralized bone matrix.

PMID- 29644313
TI  - Hafnia alvei: A new pathogen in open fractures.
AB  - Background: Deep infection following open both bone forearm fractures is a rare
      complication. Prophylactic antibiotic regimens are targeted at the most common
      pathogens, which include primarily Staph aureus followed by gram-negative
      bacteria. Hafnia alvei is an unusual pathogen that is rarely pathogenic in humans
      and has never been reported as a cause of infection following open fracture.
      Methods: We present a 12-year-old male with an open forearm fracture who
      developed a late deep infection. Cultures grew only Hafnia alvei. The patient was
      treated with debridement, placement of antibiotic beads, and ciprofloxacin.
      Results: At 6 months following the initial debridement, the patient had no
      clinical evidence of infection and regained full function of the affected forearm
      without any residual deficits. Conclusions: This is the first report of deep
      infection following an open forearm fracture owing to Hafnia alvei, a pathogen
      rarely responsible for human infection.

PMID- 29644314
TI  - Complete femoral artery transection following handlebar trauma.
AB  - Complete transection of the common femoral artery is more frequent after
      penetrating injuries than after blunt trauma, with most of the cases occurring in
      combination with fractures. Contusion from a bicycle handlebar is a rare form of
      injury to the femoral vessels. Hereby, we present a case of complete common
      femoral artery transection caused by a direct bicycle handlebar trauma. The
      patient suffered severe hypovolemia during his transfer to the Emergency room. He
      required an emergency intervention and a bypass reconstruction.

PMID- 29644315
TI  - Limb salvage and reconstruction following a zebra attack.
AB  - Animal bites are fairly rare events but can cause devastating traumatic injuries
      to the victim. In addition to the soft tissue, vascular, and orthopedic trauma
      inflicted by these occurrences, bite injuries also have the potential to
      introduce an inoculum of microbes, which may progress to an infection if not
      treated properly and expeditiously. We present the case of a healthy male who
      sustained multiple bite wounds from a domestic zebra to his left upper extremity.
      This attack caused severe damage, including devascularization of the arm at the
      brachial artery, disruption of the distal biceps and brachialis, stripping of the
      forearm nerves, and shearing of the overlying soft tissue. The patient was taken
      emergently to the operating room for revascularization of the extremity utilizing
      a vein bypass graft. The soft tissue injuries were addressed with numerous
      irrigation and debridement procedures, during which coverage of the vein bypass
      graft was obtained using a variety of techniques, including skin flaps,
      musculocutaneous advancements, and the application of an acellular dermal matrix
      (AlloDerm) and a collagen-glycosaminoglycan matrix (Integra). Wound cultures
      obtained intra-operatively during the irrigation and debridement procedures were
      notable for the growth of multiple microbes, including Rhodococcus spp., which
      have been documented to cause infection in immunocompromised patients. The
      patient in this case was treated with a prolonged course of antibiotics, and
      wound cultures negative for microbial growth were eventually obtained prior to
      final closure of his wound. The patient then underwent successful biceps
      reconstruction with a pedicled latissimus dorsi muscle transfer. This case
      documents the extraordinary multidisciplinary approach provided in the salvage,
      management, and eventual reconstruction of a mangled left upper extremity that
      had sustained devastating traumatic injuries resulting from a rather unusual
      source.

PMID- 29644316
TI  - Managing a grossly comminuted and infected mandibular fracture using a maxillary
      extra-oral distractor as stabilizing agent: A clinical case report.
AB  - Facial fracture management dates as early as Hippocratic era. Comminuted
      mandibular fractures are one of the challenging clinical condition requiring high
      surgical expertise to achieve a good functional and esthetic outcome. In presence
      of infection and other facial fractures managing comminuted mandibular fracture
      becomes more challenging. Here we present a case of grossly comminuted and
      infected mandibular fracture with delayed presentation managed by using maxillary
      distractor as stabilizing agent. Using a maxillary distractor for managing a
      fractured mandible has been seldom reported in literature. Current case report
      gives idea to practicing clinician about the possibility of treatment beyond the
      established principles.

PMID- 29644317
TI  - A rare case of Hoffa fracture combined with lateral patellar dislocation.
AB  - The coronal unicondylar fracture of the distal femur (AO 33-B3) is a rare
      intraarticular injury within the weight bearing area of the knee, initially
      described by Albert Hoffa in 1904. We report an unusual combination of a Hoffa
      fracture with lateral patellar dislocation in a young adult. Our patient
      sustained the injury by a sudden twist of his leg during sports. He presented
      clinically with knee swelling, dislocation of the patella, and localized
      tenderness; unable to bare weight. After plane radiograph confirmed the injury,
      manual reduction of the patella was done by hyperextension of the knee and
      medialward pressure. Afterwards, a CT scan and MRI were conducted. The injury was
      surgically treated with lag-screws, locking-plate and MPFL-reconstruction.

PMID- 29644318
TI  - Radiographically occult perforation and dissection of the common carotid artery
      following stab injury to the neck.
AB  - In recent years, many diagnostic algorithms have been devised to reduce the rate
      of negative explorations associated with indiscriminate surgical management of
      penetrating neck injuries. In hemodynamically stable patients, the need for
      surgical intervention is usually determined by integrating both clinical signs
      and radiological findings; if such investigations remain unremarkable,
      recommended treatment consists in close observation and sequential physical
      examinations. We report on a 29-year-old male who was admitted to a Swiss
      tertiary care hospital after sustaining a penetrating injury to his left neck
      following a knife attack. Disregarding a pre-hospital account of hemorrhage from
      the wound and slight dysphagia, no manifest symptoms or signs of internal organ
      damage were present on primary survey. Moreover, there was no evidence of
      vascular or aerodigestive tract injury on initial CT angiography. We nonetheless
      proceeded with immediate surgical exploration, exposing a significant perforation
      of the left common carotid artery with concomitant dissection of the said vessel.
      Surgical repair was successfully performed and the patient suffered no long-term
      sequelae. We thus recommend that a high level of suspicion be upheld in both
      asymptomatic and oligosymptomatic patients with PNI and that clinical
      practitioners remain cautious in the face of deceptively reassuring radiologic
      findings.

PMID- 29644320
TI  - Isolated and stable gallbladder perforation in a 5 year old child after blunt
      abdominal trauma.
AB  - Isolated gallbladder injury, secondary to a blunt abdominal trauma, is a rare
      finding in children. The presence of vague symptoms and the unknown dynamic of
      the trauma may increase the diagnostic challenge especially in pediatrics. A
      conservative management has been proposed in some particular cases in adults, but
      remains controversial in children. We report a case of a 5 year old boy who
      presented an isolated gallbladder lesion secondary to a blunt abdominal trauma.
      The surgical treatment was delayed for non-medical reasons, which gave us the
      possibility to try a conservative approach.

PMID- 29644319
TI  - Traumatic pediatric shoulder fracture dislocation treated with closed reduction
      and intramedullary nailing: A case report.
AB  - Background: Although rare, pediatric proximal humerus fractures may coexist with
      glenohumeral dislocations. Most of these injuries are Salter -Harris type of
      injuries. The treatment usually consists of closed or open reduction and k- wires
      fixation. The case: In this case report; a 10-year-old girl presented with a rare
      traumatic humeral surgical neck fracture with a posterior shoulder dislocation
      that was treated by closed reduction and flexible intramedullary nailing.
      Conclusion: Pediatric humerus fracture dislocations are rare. Treatment should
      keep in mind preservation of the growth plate.

PMID- 29644321
TI  - Delayed traumatic parasternal hernia causes jejunal necrosis: A case report.
AB  - Diaphragmatic injury is a common clinical condition, and it may be difficult to
      avoid diaphragmatic hernia if detection and treatment is not timely. Parasternal
      hernia is mostly congenital. It is relatively rare in adults, and intestinal
      obstruction as a complication of intrathoracic intestinal herniation occurs only
      rarely. We treated a patient in whom parasternal hernia occurred 2 years after
      thoracic injuries. We present the plain radiography and computed tomography
      findings of this adult patient with acute abdomen symptoms caused by parasternal
      hernia.

PMID- 29644322
TI  - Conservative treatment of periprosthetic femur fractures around metaphyseal short
      stems - A feasible option?
AB  - Periprosthetic femoral fractures are rare but significant events following total
      hip replacement. Metaphyseal short stems have recently been popularized as a bone
      preserving alternative to conventional uncemented total hip replacement. We
      present two periprosthetic femur fractures which occurred around two different
      metaphyseal uncemented stem designs. Successful conservative treatment was
      possible in both cases achieving bony union and excellent clinical results.

PMID- 29644323
TI  - Stuffing the nail: A simple technique for the extraction of a broken femoral
      nail.
AB  - The extraction of broken femoral nails can be a challenging procedure and
      surgeons should be familiar with many different techniques. This paper
      demonstrates a case study and new, simple and cost effective technique for the
      removal of broken cannulated femoral nails. Our technique uses two guide wires of
      variable diameter and had several key points of differentiation from previous
      methods. Firstly, stuffing the nail with guide wires of greater total diameter
      than the cannula; secondly, reversing the second guide wire and finally, bending
      the tips of the wires. These innovations allow the technique to be used for
      narrow cannulated nails, superior purchase along the length of the nail, easy
      wire insertion and limited soft tissue damage. Our technique for the removal of
      broken femoral nails is quick, effective, cheap and easy to replicate and can be
      used by any generalist orthopaedic surgeon with basic equipment.

PMID- 29644324
TI  - Gunshot wounds to the buttock and contralateral thigh presenting with intestinal
      injury without history of abdominal trauma. Case report.
AB  - We present a clinical case of a patient who sustained a gunshot wounds to his
      right buttock (entrance), left thigh (exit), and right thumb, as well as
      intestinal injuries without history of abdominal trauma. Initially the abdominal
      injuries were not recognised and the patient did not mention an injury to the
      abdomen. For this reason he was unfortunately admitted to the orthopaedic ward
      first for further treatment of his thumb injury.

PMID- 29644325
TI  - One-third tubular 3.5 mm Locking Compression Plate: A simple technique for
      increasing mechanical stability and reducing complications associated with
      lateral malleolar fracture surgery.
AB  - The disadvantages of the one-third-tubular plate construct to stabilize lateral
      malleolar fractures include; difficulty achieving adequate cancellous screw
      thread purchase in the bone of the distal fragment, with subsequent risk of the
      screws backing out. This can cause irritation and pain, and may require further
      surgery to remove the screw. We describe a variation of the standard technique
      that eliminates the risk of the distal lateral malleolar screws backing out and
      provides a lower profile construct. This has the potential advantages of reduced
      wound related problems and less postoperative pain and irritation.

PMID- 29644326
TI  - Trans-colonic foreign body penetration of the retro-hepatic vena cava. Report of
      a case and review of the literature.
AB  - Foreign body ingestion is common in mentally impaired adults. Fortunately, the
      vast majority of all swallowed objects pass through the gastrointestinal tract
      uneventfully. For patients in whom conservative treatment fails, early endoscopic
      intervention is required. Surgery is seldom indicated and reports of perforation
      or penetration of the GI tract are anecdotal. We present a case of a 32 years old
      mentally impaired patient with a trans-colonic penetration of a foreign body into
      the retro-hepatic vena cava.

PMID- 29644327
TI  - Regional tract-specific white matter hyperintensities are associated with
      patterns to aging-related brain atrophy via vascular risk factors, but also
      independently.
AB  - Introduction: We sought to investigate associations of regional white matter
      hyperintensities (WMHs) within white matter (WM) tracts with cardiovascular risk
      and brain aging-related atrophy throughout adulthood in the general population,
      leveraging state of the art pattern analysis methods. Methods: We analyzed a
      large sample (n = 2367) from the Study of Health in Pomerania, Germany (range 20
      90 years). WMHs were automatically segmented on T1-weighted and fluid-attenuated
      inversion recovery magnetic resonance images, and WMH volumes were calculated in
      WM regions defined using the John Hopkins University WM tractography atlas.
      Regions with the highest average WMH volume were selected. We calculated a
      subject-specific index, Spatial Pattern of Alteration for Recognition of Brain
      Aging, to measure age-related atrophy patterns. The Framingham cardiovascular
      disease risk score summarized the individual cardiovascular risk profile. We used
      structural equation models, independently for each region, using Spatial Pattern
      of Alteration for Recognition of Brain Aging as a dependent variable, age as an
      independent variable, and cardiovascular disease risk score and regional WMH
      volumes as mediators. Results: Selected 12 WM regions included 75% of the total
      WMH burden in average. Structural equation models showed that the age effect on
      Spatial Pattern of Alteration for Recognition of Brain Aging was mediated by WMHs
      to a different extent in the superior frontal WM, anterior corona radiata,
      inferior frontal WM, superior corona radiata, superior longitudinal fasciculus,
      middle temporal WM, posterior corona radiata, superior parietal WM, splenium of
      corpus callosum, posterior thalamic radiation, and middle occipital WM (variance
      explained between 2.8% and 10.3%, P < .0001 Bonferroni corrected), but not in
      precentral WM. Conclusions: Our results indicate that WMHs, in most WM tracts,
      might accelerate the brain aging process throughout adulthood in the general
      population as a result of vascular risk factors, but also independent of them.
      Preventive strategies against WMHs (such as controlling vascular risk factors or
      microglia depletion) could delay brain aging.

PMID- 29644328
TI  - Techniques for ovarian tissue transplantation and results.
AB  - Fertility preservation has emerged as a field of growing interest thanks to
      increasingly effective cancer treatments in women. For young women with good
      prospects of surviving cancer, fertility preservation counseling before
      gonadotoxic treatment is imperative to offer them a potential chance of future
      childbearing. Ovarian tissue cryopreservation and transplantation emerges as a
      strategy for fertility preservation, especially for prepubertal girls,
      adolescents and women in whom cancer treatment cannot be delayed. Numerous
      surgical techniques have been reported and are currently being used for frozen
      thawed ovarian tissue reimplantation, but successful approaches all adhere to the
      same fundamental micro-surgical principles: 1) finding a well vascularized
      orthotopic transplantation site, and 2) fixing the ovarian tissue by means of
      stitches, Interceed(r) and/or fibrin glue. Orthotopic reimplantation has proved
      to be the most effective technique in terms of resumption of ovarian endocrine
      function in more than 95% of all reported cases, and fertility restoration in
      over than 40% of patients in our series.

PMID- 29644329
TI  - Ovarian endometriosis and fertility preservation: a challenge in 2018.
AB  - Endometriosis is a benign, estrogen-dependent gynecological disorder. It is now
      well established that three different forms of endometriosis can occur in the
      pelvic cavity, namely peritoneal endometriosis, ovarian endometriosis and deep
      endometriotic nodules of the rectovaginal septum. Treatment of endometriosis
      associated infertility has been investigated using both medical and surgical
      modalities. Surgery for ovarian endometriosis can lead to premature ovarian
      insufficiency (POI) and further infertility, so one of the most important goals
      of therapy should be preserving fertility. Procedures combining stripping and
      ablation should be considered the first-line approach for ovarian endometrioma
      related infertility, in order to protect the ovarian reserve, which may already
      be depleted even before surgery. Autotransplantation of ovarian tissue should be
      considered in case of mandatory radical treatment (oophorectomy), or if
      conservative treatment poses a risk. For patients at risk of POI, particularly
      those undergoing gonadotoxic treatment, two main fertility preservation options
      exist: oocyte vitrification or reimplantation of fresh or frozen ovarian tissue.
      Both have advantages and disadvantages.

PMID- 29644330
TI  - Pregnancy complications in infertile patients with polycystic ovary syndrome:
      updated evidence.
AB  - Polycystic ovary syndrome (PCOS) is a common female disorder with a pathogenesis
      still today not completely known. To the present, PCOS is considered more than
      just a reproductive disorder since several metabolic consequences that could
      affect women's health during different stages of reproductive and post
      reproductive life were reported. The aim of the current review was to evaluate
      present evidence-based data regarding the pregnancy complications in infertile
      patients with PCOS. An extensive literature search until February 2018 was
      performed in PubMed, Medline, the Cochrane Library and Web of Science. Outcomes
      were classified in: early pregnancy complications, late pregnancy complications,
      perinatal complications, offspring health and long-term offspring and maternal
      health. Even if the exact mechanisms involved are still unclear, women with PCOS
      have an increased risk of pregnancy-related complications, such as gestational
      diabetes mellitus (GDM), pregnancy-induced hypertension (PIH), preeclampsia (PE),
      premature delivery and caesarean section. Moreover, the offspring of women with
      PCOS are also at increased risk of congenital anomalies and hospitalization in
      childhood. Further studies are needed to study the mechanism underlying pregnancy
      complications in PCOS and to identify any interventions to reduce the risk of
      obstetric and neonatal risks in women affected by PCOS and in their offspring.

PMID- 29644331
TI  - From isolation of human ovarian follicles to the artificial ovary: tips and
      tricks.
AB  - Cryopreservation and transplantation of ovarian tissue has proved to restore both
      endocrine and reproductive functions in cancer patients. However, women with a
      high risk of ovarian involvement cannot undergo ovarian tissue transplantation
      due to possible recurrence of the disease. Therefore, different teams worldwide
      are now working on the development of experimental strategies, like the
      transplantable artificial ovary (TAO), with the noble goal to offer to these
      patients hope for future conception. This article discusses some essential points
      for the creation of a TAO and reviews the latest progress made.

PMID- 29644332
TI  - Indications for fertility preservation in women from malignant diseases to benign
      conditions to age-related fertility decline.
AB  - Oocyte vitrification and ovarian tissue cryopreservation are two common fertility
      preservation options. Oocyte vitrification provides the highest yield for women
      with benign diseases or those seeking fertility preservation for age-related
      fertility decline. This technique is also indicated for cancer women if cancer
      treatment can be postponed. Ovarian tissue cryopreservation has some specific
      indications. There is indeed no other alternative for fertility preservation in
      prepubertal girls, and in cancer women in whom cancer treatment cannot be
      postponed. This review focuses on the indications for fertility preservation from
      malignant diseases to benign conditions to age-related fertility decline.

PMID- 29644333
TI  - Risk of transplanting malignant cells in cryopreserved ovarian tissue.
AB  - Improvements in cancer treatments have increased the chances of survival of young
      cancer patients, but have given rise to other issues, like premature ovarian
      insufficiency and infertility. Preservation and subsequent restoration of ovarian
      function in these patients is now possible thanks to ovarian tissue
      cryopreservation and transplantation. However, safety concerns about the possible
      presence of cancerous cells in the tissue to be cryopreserved must be addressed.
      Indeed, reimplantation of malignant cell-contaminated ovarian tissue could
      potentially lead to recurrence of the primary disease. This review of the
      existing literature aims to evaluate the risk of reintroducing malignant cells in
      pathologies that represent the main indications for ovarian tissue
      cryopreservation. Experimental studies applying molecular analyses as well as
      xenografting investigation have proved that hematologic and ovarian malignancies
      are those at greatest risk of ovarian involvement, and hence recurrence upon
      reimplantation of frozen-thawed ovarian tissue. Preimplantation analysis using
      highly sensitive techniques and disease-specific markers is therefore vital in
      these patients to detect minimal disseminate disease.

PMID- 29644334
TI  - Objective measurement in routine care of people with Parkinson's disease improves
      outcomes.
AB  - It is common in medicine to titrate therapy according to target ranges of
      objectively measured parameters. Objective measurement of motor function is
      available for Parkinson's Disease (PD), making it possible to optimise therapy
      and clinical outcomes. In this study, an accelerometry based measurement and
      predefined target ranges were used to assess motor function in a Northern
      Tasmania PD cohort managed by a Movement Disorder clinic. Approximately 40% (n =
      103) of the total PD population participated in this study and motor scores were
      within target in 22%. In the 78% above target, changes in oral therapy were
      recommended in 74%, Advanced Therapy in 12% and treatment was contraindicated in
      9%. Following changes in oral therapy, there was a further objective measurement
      and clinical consultation to establish whether scores had reached target range:
      if so subjects left the study, otherwise further changes of therapy were
      recommended (unless contraindications were present). Seventy-seven cases
      completed the study, with 48% achieving target (including 22% at outset),
      Advanced Therapy recommended in 19% and contraindications preventing any change
      in therapy in 17%. In the 43% of cases in whom oral therapy was changed, total
      UPDRS improved significantly (effect size = 8) as did the PDQ39 in cases reaching
      target. NMS Quest and MOCA scores also improved significantly. This study shows
      that many people in a representative cohort of PD would benefit from objective
      assessment and treatment of their PD features against a target.

PMID- 29644337
TI  - Novel, Moon and Mars, partial gravity simulation paradigms and their effects on
      the balance between cell growth and cell proliferation during early plant
      development.
AB  - Clinostats and Random Positioning Machine (RPM) are used to simulate
      microgravity, but, for space exploration, we need to know the response of living
      systems to fractional levels of gravity (partial gravity) as they exist on Moon
      and Mars. We have developed and compared two different paradigms to simulate
      partial gravity using the RPM, one by implementing a centrifuge on the RPM
      (RPMHW), the other by applying specific software protocols to driving the RPM
      motors (RPMSW). The effects of the simulated partial gravity were tested in plant
      root meristematic cells, a system with known response to real and simulated
      microgravity. Seeds of Arabidopsis thaliana were germinated under simulated Moon
      (0.17 g) and Mars (0.38 g) gravity. In parallel, seeds germinated under simulated
      microgravity (RPM), or at 1 g control conditions. Fixed root meristematic cells
      from 4-day grown seedlings were analyzed for cell proliferation rate and rate of
      ribosome biogenesis using morphometrical methods and molecular markers of the
      regulation of cell cycle and nucleolar activity. Cell proliferation appeared
      increased and cell growth was depleted under Moon gravity, compared with the 1 g
      control. The effects were even higher at the Moon level than at simulated
      microgravity, indicating that meristematic competence (balance between cell
      growth and proliferation) is also affected at this gravity level. However, the
      results at the simulated Mars level were close to the 1 g static control. This
      suggests that the threshold for sensing and responding to gravity alteration in
      the root would be at a level intermediate between Moon and Mars gravity. Both
      partial g simulation strategies seem valid and show similar results at Moon g
      levels, but further research is needed, in spaceflight and simulation facilities,
      especially around and beyond Mars g levels to better understand more precisely
      the differences and constrains in the use of these facilities for the space
      biology community.

PMID- 29644336
TI  - Limitations in predicting the space radiation health risk for exploration
      astronauts.
AB  - Despite years of research, understanding of the space radiation environment and
      the risk it poses to long-duration astronauts remains limited. There is a
      disparity between research results and observed empirical effects seen in human
      astronaut crews, likely due to the numerous factors that limit terrestrial
      simulation of the complex space environment and extrapolation of human clinical
      consequences from varied animal models. Given the intended future of human
      spaceflight, with efforts now to rapidly expand capabilities for human missions
      to the moon and Mars, there is a pressing need to improve upon the understanding
      of the space radiation risk, predict likely clinical outcomes of interplanetary
      radiation exposure, and develop appropriate and effective mitigation strategies
      for future missions. To achieve this goal, the space radiation and aerospace
      community must recognize the historical limitations of radiation research and how
      such limitations could be addressed in future research endeavors. We have sought
      to highlight the numerous factors that limit understanding of the risk of space
      radiation for human crews and to identify ways in which these limitations could
      be addressed for improved understanding and appropriate risk posture regarding
      future human spaceflight.

PMID- 29644338
TI  - Hypothesis: can the abscopal effect explain the impact of adjuvant radiotherapy
      on breast cancer mortality?
AB  - Radiotherapy is an integral component of loco-regional therapy for breast cancer.
      Randomized controlled trials indicate that increasing the extent of extirpative
      surgery primarily reduces the risk of local recurrences, while the addition of
      radiotherapy to surgery can also reduce the risk of distant recurrences, thereby
      lowering breast cancer-specific mortality. This may suggest an "abscopal" effect
      beyond the immediate zone of loco-regional irradiation that favorably perturbs
      the natural history of distant micrometastases. Immunological phenomena such as
      "immunogenic cell death" provide a plausible mechanistic link between the local
      and systemic effects of radiation. Radiotherapy treatment can stimulate both pro
      immunogenic and immunosuppressive pathways with a potential net beneficial effect
      on anti-tumor immune activity. Upregulation of programmed cell death ligand (PD
      L1) by radiotherapy is an immunosuppressive pathway that could be approached with
      anti-PD-L1 therapy with potential further improvement in survival. The world
      overview of randomized trials indicates that the breast cancer mortality
      reduction from adjuvant radiotherapy is delayed relative to that of adjuvant
      systemic treatments, and similar delays in the separation of survival curves are
      evident in the majority of randomized immunotherapy trials demonstrating
      treatment efficacy. In this article, we hypothesize that an abscopal effect may
      explain the benefit of radiotherapy in reducing breast cancer mortality, and that
      It might be possible to harness and augment this effect with systemic agents to
      reduce the risk of late recurrences.

PMID- 29644335
TI  - Neuromelanin detection by magnetic resonance imaging (MRI) and its promise as a
      biomarker for Parkinson's disease.
AB  - The diagnosis of Parkinson's disease (PD) occurs after pathogenesis is advanced
      and many substantia nigra (SN) dopamine neurons have already died. Now that
      therapies to block this neuronal loss are under development, it is imperative
      that the disease be diagnosed at earlier stages and that the response to
      therapies is monitored. Recent studies suggest this can be accomplished by
      magnetic resonance imaging (MRI) detection of neuromelanin (NM), the
      characteristic pigment of SN dopaminergic, and locus coeruleus (LC) noradrenergic
      neurons. NM is an autophagic product synthesized via oxidation of catecholamines
      and subsequent reactions, and in the SN and LC it increases linearly during
      normal aging. In PD, however, the pigment is lost when SN and LC neurons die. As
      shown nearly 25 years ago by Zecca and colleagues, NM's avid binding of iron
      provides a paramagnetic source to enable electron and nuclear magnetic resonance
      detection, and thus a means for safe and noninvasive measure in living human
      brain. Recent technical improvements now provide a means for MRI to differentiate
      between PD patients and age-matched healthy controls, and should be able to
      identify changes in SN NM with age in individuals. We discuss how MRI detects NM
      and how this approach might be improved. We suggest that MRI of NM can be used to
      confirm PD diagnosis and monitor disease progression. We recommend that for
      subjects at risk for PD, and perhaps generally for older people, that MRI
      sequences performed at regular intervals can provide a pre-clinical means to
      detect presymptomatic PD.

PMID- 29644339
TI  - Molecular characterization of two sub-family specific monoclonal antibodies to
      meningococcal Factor H binding protein.
AB  - Factor H binding protein (FHbp) is a component of two licensed vaccines for
      prevention of sepsis and meningitis caused by serogroup B meningococci. FHbp
      binds human Factor H (FH), which contributes to evasion of host immunity and FHbp
      sequence variants can be classified into two sub-families. Antibodies against
      FHbp elicit complement-mediated killing and can inhibit recruitment of FH to the
      bacterial surface. We report epitope mapping studies of two murine IgG mAbs,
      designated JAR 31 and JAR 36, isolated from a mouse immunized with FHbp in sub
      family A, which is present in ~30-40% of invasive isolates. In the present study,
      we tested the reactivity of mAbs JAR 31 and JAR 36 with seven natural FHbp
      sequence variants from different phylogenic groups. We screened bacteriophage
      displayed peptide libraries to identify amino acid residues contributing to the
      JAR 36 epitope. Based on the reactivities of mAbs JAR 31 and JAR 36 with the
      seven FHbp variants, and the frequent occurrences of aspartate (D) and lysine (K)
      residues in the JAR 36-bound phage peptides, we selected six residues in the
      carboxyl-terminal region of FHbp for replacement with alanine (A). The D201A and
      K203A substitutions respectively eliminated and decreased binding of mAbs JAR 31
      and JAR 36 to FHbp. These substitutions did not affect binding of the control mAb
      JAR 33 or of human FH. JAR 31 or JAR 36 mediated cooperative complement-mediated
      bactericidal activity with other anti-FHbp mAbs. The identification of two amino
      acid residues involved in the epitopes recognized by these anti-FHbp mAbs may
      contribute to a more complete understanding of the spatial requirements for
      cooperative anti-FHbp mAb bactericidal activity.

PMID- 29644340
TI  - The Lateralizing Asymmetry of Adrenal Adenomas.
AB  - Context: It is presumed that the incidence of adrenal adenomas is symmetric
      between the left and right adrenal gland; however, anecdotal observations suggest
      a potential lateralizing asymmetry. Objective: To investigate the symmetry in
      detection of adrenal adenomas and relevance to patient care. Design: Cross
      sectional and longitudinal studies. Population and Setting: One thousand three
      hundred seventy-six patients with abdominal computed tomography or magnetic
      resonance imaging demonstrating benign-appearing adrenal adenomas. Main Outcome:
      Location and size of adrenal adenomas. Results: Left-sided adenomas were
      discovered in 65% of patients, right-sided in 21%, and bilateral adenomas in 14%.
      Among unilateral adenomas, 75% were left-sided. Left-sided adenomas were more
      prevalent than right-sided adenomas in each size category except the largest: <10
      mm, 87%; 10 to 19 mm, 74%; 20 to 29 mm, 72%; >=30 mm, 56% (P < 0.0001 for each
      category, except P = 0.19 when >=30 mm). Among those with bilateral adenomas, the
      left-sided adenoma was significantly larger than the right one in 61% of patients
      (P < 0.001). There were no significant differences in the baseline prevalence or
      incidence of cardiometabolic diseases between patients with left-sided vs right
      sided adenomas during 5.10 (4.2) years of follow-up. Conclusions: Adrenal
      adenomas are substantially more likely to be identified on the left adrenal than
      the right. This observation may be due to detection bias attributed to the
      location of the right adrenal, which may preclude identification of right-sided
      adenomas until they are substantially larger. These findings suggest the
      potential for an underrecognition of right-sided adenomas that may also impair
      the accurate detection of bilateral adrenal diseases.

PMID- 29644341
TI  - Uptake of 99mTc-MIBI by Sclerosing Pneumocytoma Raising a False Suspicion of
      Metastasis From Medullary Thyroid Carcinoma.
AB  - Technetium-99m methoxy isobutyl isonitrile (99mTc-MIBI; sestamibi) single-photon
      emission computed tomography (SPECT)/computed tomography (CT) performed for
      preoperative localization of parathyroid adenomas or for other indications can
      reveal incidentalomas. Interpretation of such findings can be challenging,
      particularly when thyroid or other endocrine tumors are also present.
      Preoperative staging of a 59-year-old female patient with medullary thyroid
      carcinoma (MTC) showing moderate hypermetabolism on 18F-fluorodeoxyglucose
      positron emission tomography/CT also detected a slightly hypermetabolic pulmonary
      nodule (standardized uptake value normalized by body weight max = 2.0 g/mL). A
      sestamibi SPECT/CT performed because of concomitant primary hyperparathyroidism
      showed increased uptake by both the MTC and the pulmonary nodule, raising
      suspicion of MTC metastasis. Lung wedge resection biopsy revealed a sclerosing
      pneumocytoma (SPC), a rare benign pulmonary tumor not previously known to retain
      sestamibi. In contrast to classical knowledge that sestamibi uptake by tumors is
      associated with its retention by mitochondria, immunohistochemical analyses
      showed that the mitochondrial content of the patient's SPC was low. This case
      illustrates the behavior of SPC in sestamibi scintigraphy and indicates that SPC
      is a potential cancer mimicker in this setting.

PMID- 29644343
TI  - Reaching Out to Residents of Remote Islands of Maine.

PMID- 29644342
TI  - Epigenetic Basis of Clozapine Action.

PMID- 29644344
TI  - Patient Centered Hazard Ratio Estimation Using Principal Stratification Weights:
      Application to the NORCCAP Randomized Trial of Colorectal Cancer Screening.
AB  - In randomized trials, the most commonly reported method of effect estimation is
      intention-to-treat (ITT), and to a lesser extent the per-protocol. The ITT is
      preferred because it is an unbiased estimator of the effect of treatment
      assignment. However, if there is any non-adherence the ITT is a biased estimate
      of the treatment effect, defined as the contrast between the potential outcome if
      treated versus the potential outcome if not treated. The treatment effect is most
      relevant to patients. Principal stratification is a framework for estimating
      treatment effects that combines potential outcomes and latent adherence strata.
      It yields an unbiased estimator of the complier average causal effect (CACE) for
      a difference in means or proportions, in the setting of all-or-nothing adherence.
      This paper addresses estimation of the causal hazard ratio for the compliers in a
      setting of right censoring of a time-to-event. We propose a novel approach to
      operationalizing principal stratification using weights. We report the results of
      simulations that vary the amount of adherence and selection bias that show the
      hazard ratio estimators we propose have minimal bias compared to the ITT, and per
      protocol estimators. We demonstrate the approach using a population based
      randomized controlled trial of colorectal cancer screening subject to a high
      frequency of nonadherence in the screening arm.

PMID- 29644345
TI  - Online Conditional Outlier Detection in Nonstationary Time Series.
AB  - The objective of this work is to develop methods for detecting outliers in time
      series data. Such methods can become the key component of various monitoring and
      alerting systems, where an outlier may be equal to some adverse condition that
      needs human attention. However, real-world time series are often affected by
      various sources of variability present in the environment that may influence the
      quality of detection; they may (1) explain some of the changes in the signal that
      would otherwise lead to false positive detections, as well as, (2) reduce the
      sensitivity of the detection algorithm leading to increase in false negatives. To
      alleviate these problems, we propose a new two-layer outlier detection approach
      that first tries to model and account for the nonstationarity and periodic
      variation in the time series, and then tries to use other observable variables in
      the environment to explain any additional signal variation. Our experiments on
      several data sets in different domains show that our method provides more
      accurate modeling of the time series, and that it is able to significantly
      improve outlier detection performance.

PMID- 29644346
TI  - Detoxifying symbiosis: microbe-mediated detoxification of phytotoxins and
      pesticides in insects.
AB  - Covering: up to 2018 Insects live in a world full of toxic compounds such as
      plant toxins and manmade pesticides. To overcome the effects of these toxins,
      herbivorous insects have evolved diverse, elaborate mechanisms of resistance,
      such as toxin avoidance, target-site alteration, and detoxification. These
      resistance mechanisms are thought to be encoded by the insects' own genomes, and
      in many cases, this holds true. However, recent omics analyses, in conjunction
      with classic culture-dependent analyses, have revealed that a number of insects
      possess specific gut microorganisms, some of which significantly contribute to
      resistance against phytotoxins and pesticides by degrading such chemical
      compounds. Here, we review recent advances in our understanding on the symbiont
      mediated degradation of natural and artificial toxins, with a special emphasis on
      their underlying genetic basis, focus on the importance of environmental
      microbiota as a resource of toxin-degrading microorganisms, and discuss the
      ecological and evolutionary significance of these symbiotic associations.

PMID- 29644348
TI  - Degradation of thin-film lithium batteries characterised by improved
      potentiometric measurement of entropy change.
AB  - The degradation phenomena of thin-film solid state batteries caused by cycling at
      a high cut-off voltage and different temperatures were studied using an improved
      potentiometric measurement of entropy change combined with electrochemical
      impedance analysis and incremental capacity analysis. Entropy profiling is
      demonstrated as a viable non-destructive technique for solid state batteries that
      is sensitive to structural changes in electrodes during galvanostatic cycling,
      and is complementary to other techniques for studying degradation. The
      characteristic peaks and valleys in the entropy profile as a function of the
      state-of-charge could be closely correlated to theories of phase transitions in
      the cathode material. This technique is therefore a useful technique to help
      understand and diagnose the degradation mechanism, and specify the state-of
      health in a promising new battery technology.

PMID- 29644347
TI  - Bioaccessible selenium sourced from Se-rich mustard cake facilitates protection
      from TBHP induced cytotoxicity in melanoma cells.
AB  - Selenium (Se) is an essential dietary supplement that resolves inflammatory
      responses and offers antioxidant cytoprotection. In this study, we present the
      data on the cytoprotective effect of Se-rich mustard protein isolated from
      mustard cultivated in seleniferous soils in Punjab, India. The concentrations of
      total Se in mustard seed, oil-free mustard cake, and mustard protein were 110.0
      +/- 3.04, 143.0 +/- 5.18, and 582.3 +/- 6.23 MUg g-1, respectively. The
      cytoprotective effect of Se-rich mustard protein was studied on tert-butyl
      hydroperoxide (TBHP)-induced cytotoxicity in a mouse melanoma cell line (B16
      F10). When compared with TBHP treated cells (where no viable cells were found),
      Se-rich protein made bioaccessible through simulated gastrointestinal digestion
      protected melanoma cells from cytotoxicity with decreased levels of oxidative
      stress resulting in 73% cell viability. Such an effect was associated with a
      significant increase in glutathione peroxidase activity as a function of
      bioaccessible Se and its response towards cytoprotection.

PMID- 29644354
TI  - In situ synthesis of metal clusters encapsulated within small-pore zeolites via a
      dry gel conversion method.
AB  - We report here a facile strategy for encapsulating Pt clusters into MFI crystals
      via a dry gel conversion (DGC) method, by introducing Pt-immobilized Schiff-SiO2
      as the silicon resource. This protocol involves a solid phase transformation
      process for crystallization which occurs without significant deconstruction of
      the structure of the Pt-containing precursor. High-angle annular dark-field
      scanning transmission electron microscopy images indicate that most of the Pt
      clusters are less than 1 nm in size and located in defective channels or voids of
      MFI. Thanks to the encapsulation role, these Pt clusters are stable against
      sintering even after calcination at 500  degrees C and only grow up to ~2.8 nm
      after calcination at 800  degrees C. The uniform pore structure of a zeolite
      endows the Pt@zeolite catalyst with shape-selectivity for hydrogenation and
      oxidation reactions over size differentiated analog substrates. This synthesis
      method is attainable for the embedment of stable metal clusters inside the small
      pore MFI zeolite.

PMID- 29644351
TI  - Cellular uptake efficiency of nanoparticles investigated by three-dimensional
      imaging.
AB  - Understanding the interaction of nanoparticles with living cells on the basis of
      cellular uptake efficiency is a fundamental requisite in biomedical research.
      Cellular internalization of nanoparticles takes place by mechanisms like ATP
      hydrolysis-driven endocytosis that deliver nanoparticles to the cytoplasm,
      organelles and nuclei. Despite its importance in nanomedicine, this uptake
      procedure is not understood in-depth because of the complexity of the biochemical
      mechanisms and the lack of available experimental methods for quantitative
      analysis. The only breakthrough is likely to be the development of imaging
      techniques that can visualize, monitor and even count the number of nanoparticles
      inside the cell. To this end, we report here a new, fast and background-free
      three-dimensional (3-D) imaging technique with quantitative evaluation of the
      uptake efficiency for NaYF4:Yb3+,Er3+/NaYF4 core/shell upconversion nanoparticles
      (UCNPs) functionalized with different chemical and biological groups.
      Furthermore, the multiple 3-D trajectories of the UCNPs have been analyzed to
      investigate the cellular dynamics. This study reveals the nuclear uptake of UCNPs
      to be dependent on the specific chemical groups conjugated to the UCNPs. The
      developed 3-D imaging technique is of great significance for exploring complex
      biological systems.

PMID- 29644355
TI  - Carbon nanodot-induced gelation of a histidine-based amphiphile: application as a
      fluorescent ink, and modulation of gel stiffness.
AB  - This is a unique example of fluorescent carbon dot-induced hydrogelation of an
      amino acid-based amphiphile. The carbon dot-to-amphiphile ratio dictates the gel
      stiffness. Moreover, this hydrogel can be used as a prominent fluorescent ink and
      the dried gel shows a remarkable, unusual green fluorescence in the solid state.

PMID- 29644357
TI  - The inhibitory effect of Manuka honey on human colon cancer HCT-116 and LoVo cell
      growth. Part 2: Induction of oxidative stress, alteration of mitochondrial
      respiration and glycolysis, and suppression of metastatic ability.
AB  - Despite its high content of phenolic compounds, the chemopreventive activity of
      Manuka honey (MH) is still elusive. The aim of the present work was to evaluate
      the effects of MH on oxidative stress, antioxidant enzymes, cellular metabolism
      and the metastatic ability in HCT-116 and LoVo cells, paying particular attention
      to the molecular mechanisms involved. We observed a strong induction of oxidative
      stress after MH treatment since it augmented the accumulation of reactive oxygen
      species and increased the damage to proteins, lipids and DNA. Furthermore, MH
      suppressed the Nrf2-dependent antioxidant enzyme expression (superoxide dismutase
      (SOD), catalase and heme oxygenase-1) and the activity of SOD, catalase,
      glutathione peroxidase and glutathione reductase. Cell metabolisms were markedly
      disrupted after MH treatment. It decreased maximal oxygen consumption and spare
      respiratory capacity, which could reduce the mitochondrial function that is
      correlated with cell survival potential. Simultaneously, MH decreased the
      extracellular acidification rate (glycolysis) of HCT-116 and LoVo cells.
      Furthermore, MH suppressed the p-AMPK/AMPK, PGC1alpha and SIRT1 activation,
      involved in the survival of HCT-116 and LoVo cells under metabolic stress
      conditions. Dose-dependently, MH reduced the migration and invasion (MMP-2 and
      MMP-9) ability, and concurrently regulated EMT-related markers (E cadherin, N
      cadherin, and beta-catenin) in both cell types. The above findings indicate that
      MH induces HCT-116 and LoVo cell death partly by enhancing oxidative stress, as
      well as by regulating the energy metabolism in both aerobic and anaerobic
      pathways and suppressing the metastatic ability.

PMID- 29644358
TI  - Raman-encoded, multivalent glycan-nanoconjugates for traceable specific binding
      and killing of bacteria.
AB  - Glycan recognition plays key roles in cell-cell and host-pathogen interactions,
      stimulating widespread interest in developing multivalent glycoconjugates with
      superior binding affinity for biological and medical uses. Here, we explore the
      use of Raman-encoded silver coated gold nanorods (GNRs) as scaffolds to form
      multivalent glycoconjugates. The plasmonic scaffolds afford high-loading of
      glycan density and their optical properties offer the possibilities of monitoring
      and quantitative analysis of glycan recognition. Using E. coli strains with
      tailored on/off of the FimH receptors, we have demonstrated that Raman-encoded
      GNRs not only allow for real-time imaging and spectroscopic detection of specific
      binding of the glycan-GNR conjugates with bacteria of interest, but also cause
      rapid eradication of the bacteria due to the efficient photothermal conversion of
      GNRs in the near-infrared spectral window. We envision that optically active
      plasmonic glycoconjugates hold great potential for screening multivalent glycan
      ligands for therapeutic and diagnostic applications.

PMID- 29644359
TI  - Effects of methyl substitution on DNA binding enthalpies of enantiopure
      Ru(phenanthroline)2dipyridophenazine2+ complexes.
AB  - Isothermal titration calorimetry (ITC) has been utilized to investigate the
      effect of methyl substituents on the intercalating dppz ligand of the enantiomers
      of the parent complex Ru(phen)2dppz2+ (phen = 1,10-phenanthroline; dppz =
      dipyrido[3,2-a:2',3'-c]phenazine) on DNA binding thermodynamics. The methylated
      complexes (10-methyl-dppz and 11,12-dimethyl-dppz) have large, concentration
      dependent, positive heats of dilution, and a strong endothermic background is
      also apparent in the ITC-profiles from titration of methylated complexes into
      poly(dAdT)2, which make direct comparison between complexes difficult. By
      augmenting a simple cooperative binding model with one equilibrium for complex
      self-aggregation in solution and one equilibrium for complex aggregation on
      saturated DNA, it was possible to find an excellent global fit to the
      experimental data with DNA affinity parameters restricted to be equal for all
      Delta-enantiomers as well as for all Lambda-enantiomers. In general, enthalpic
      differences, compared to the unsubstituted complex, were small and less than 4 kJ
      mol-1, except for the heat of intercalation of Delta-10-methyl-dppz (-11,6 kJ mol
      1) and Lambda-11,12-dimethyl-dppz (+4.3 kJ mol-1).

PMID- 29644360
TI  - Asymmetric current-driven switching of synthetic antiferromagnets with Pt insert
      layers.
AB  - A perpendicularly magnetized synthetic antiferromagnetic structure is a promising
      alternative to a single ferromagnetic layer in spintronic applications because of
      its low net magnetization and high thermal stability. In this work, the
      ferromagnetic layers in the synthetic antiferromagnetic structure are simplified
      to 'soft' Co70Fe30 layers with the aid of ultrathin Pt insert layers between the
      ferromagnetic layers and the exchange coupling Ru layer to lower the energy
      consumption. In the current-driven manipulation of the magnetization, asymmetric
      switching loops are observed, which originate from the edge domain walls induced
      by the growth of the electrode pads. The edge domain walls preserved beneath the
      electrode pad help the switching process skipping the nucleation stage, lowering
      the critical current density to the order of 106 A cm-2. The present work
      broadens the choice of ferromagnetic layers for building an SAF structure and
      highlights a new way to utilize the synthetic antiferromagnetic structure as a
      building block in low-energy-consuming spintronic devices.

PMID- 29644361
TI  - Preparation of carbon-based AuAg alloy nanoparticles by using the heterometallic
      [Au4Ag4] cluster for efficient oxidative coupling of anilines.
AB  - We herein report the preparation of unique heteroatom-doped and carbon-based AuAg
      alloy nanoparticles (NPs) via the pyrolysis of a structurally defined octanuclear
      heterometallic Au(i)-Ag(i) cluster [Au4Ag4(Dppy)4(Tab)4(MeCN)4](PF6)8 (2, Dppy =
      diphenylphosphine-2-pyridine and Tab = 4-(trimethylammonio)benzenethiolate). This
      cluster-precursor approach exerts a fine control over the spatial arrangement,
      size and uniformity of the AuAg alloy NPs as well as the doped heteroatoms (P, N,
      F and S). The optimized material prepared at 450  degrees C efficiently catalyzes
      the oxidative coupling of anilines to yield azobenzenes under mild conditions.

PMID- 29644362
TI  - Synergetic enhancement of the electronic/ionic conductivity of a Li-ion battery
      by fabrication of a carbon-coated nanoporous SnOxSb alloy anode.
AB  - The major obstacles which prohibit the practical applications of alloy-type
      anodes include insufficient ionic/electronic transportations and structural
      failures. Herein, we report the fabrication of a carbon-coated nanoporous SnSb
      alloy (NP-SnOxSb@C) and its application as an anode in Li-ion batteries (LIBs).
      The as-fabricated NP-SnOxSb@C is characterized by SEM and TEM and demonstrates a
      bi-continuous nanoporous structure. Amorphous carbon is found to be uniformly
      coated on the alloy surface. When used as an anode for LIB, NP-SnOxSb@C displays
      a high capacity (850 mA h g-1 after the 50th cycle) and good rate performance of
      664 mA h g-1 at 2000 mA g-1. The improved electrochemical performance is mainly
      due to a high Li+ diffusion coefficient and low charge transfer resistance
      between the nanoporous structure and conductive carbon layer. The facile material
      fabrication process and good electrochemical performance enable the practical
      utilization of this anode for high-performance LIBs.

PMID- 29644363
TI  - Quantum mechanical determination of atomic polarizabilities of ionic liquids.
AB  - The distribution of a molecule's polarizability to individual atomic sites is
      inevitable to develop accurate polarizable force fields. We present the direct
      quantum mechanical calculation of atomic polarizabilities of 27 common ionic
      liquids. The method is superior to previously published distribution routines
      based on large databases of the molecular polarizability, and enables the correct
      description of any ionic liquid and its peculiarities within the quantum
      mechanical framework.

PMID- 29644364
TI  - Silicene and germanene on InSe substrates: structures and tunable electronic
      properties.
AB  - Using first-principles calculations, we show that the recently synthesized two
      dimensional (2D) van der Waals layered material indium selenide (InSe) nanosheets
      can serve as a suitable substrate for silicene and germanene, which form
      commensurate and stable silicene/InSe (Si/InSe) and germanene/InSe (Ge/InSe)
      heterolayers (HLs). The buckled honeycomb geometries and Dirac-cone-like band
      structures of silicene and germanene are well preserved in these HLs. The
      interaction between silicene (or germanene) and the InSe substrate opens up a
      band gap of 141 meV (or 149 meV) at the Dirac points, while electron effective
      masses (EEM) remain as small as 0.059 and 0.067 times the free-electron mass
      (m0). The band gap and the EEM of the HLs can be further modulated effectively by
      applying an external electric field or strain. These features are attributed to
      the built-in electric field due to the interlayer charge transfer of the HLs
      which breaks the equivalence of the two sublattices of silicene and germanene.
      Multilayer (ML) InSe substrates have also been considered. We also proposed a
      parallel plate capacitor model to describe the interaction between silicene (or
      germanene) and the InSe substrate as well as the electronic band structure
      modification in response to an external field. This work is expected to offer an
      ideal substrate material for the growth of silicene and germanene and a promising
      van der Waals (vdW) layered heterostructure for electronic devices.

PMID- 29644365
TI  - Efficient peptide ligation between allyl-protected Asp and Cys followed by
      palladium-mediated deprotection.
AB  - An efficient method for peptide ligation between C-terminal Asp(OAllyl) and N
      terminal Cys has been developed. Peptide ligation and removal of the allyl group
      at the Asp carboxylate side chain proceeded in one pot by adding a small amount
      of Pd/TPPTS complex. Based on this efficient synthetic method, PEP-19 (61 amino
      acids), which is highly expressed in Purkinje cells, was synthesized.

PMID- 29644366
TI  - Cp*Co(iii)-catalyzed amidation of olefinic and aryl C-H bonds: highly selective
      synthesis of enamides and pyrimidones.
AB  - A highly efficient and selective synthesis of enamides via C-H amidation of N
      methoxy acrylamides with dioxazolones is realized under [Cp*CoIII] catalysis. The
      resulting enamide can further selectively cyclize to form pyrimidones, which can
      also act as a directing group for a second C-H amidation. All these three classes
      of products were selectively delivered under controlled conditions.

PMID- 29644367
TI  - Three cooperative diffusion coefficients describing dynamics of polymer gels.
AB  - Cooperative diffusion coefficient (Dcoop) describes the dynamics of a polymer
      network in a gel, and is estimated by three independent methods. We measured
      three Dcoop's of a model polymer network system (Tetra-PEG gels), and obtained
      the experimental evidence to fundamentally understand the dynamics of polymer
      gels.

PMID- 29644369
TI  - Photoluminescence properties of tetrahedral zinc(ii) complexes supported by
      calix[4]arene-based salicylaldiminato ligands.
AB  - The synthesis and photophysical properties of four new hybrid salicylaldiminato
      calix[4]arene ligands and their corresponding zinc(ii) complexes are described.
      The Schiff bases were obtained from condensation reactions between cone-25,27
      di(aminoethoxy)-26,28-dihydroxy-calix[4]arene and salicylaldehyde (H2L1) or o
      vanillin (H2L2) and 1,3-alt-25,27-di(aminoethoxy)-26,28-di(n-propyloxy)
      calix[4]arene and 3,5-di-tert-butyl-salicylaldehyde (H2L3) or o-vanillin (H2L4).
      Complexation reactions were investigated by ESI-MS, IR, NMR, UV-vis absorption
      and steady-state and time resolved fluorescence spectroscopy, and X-ray
      crystallography. All ligands support 1 : 1 complexes (ZnL1-ZnL4), with
      equilibrium constants derived from absorption spectrophotometry in the range log
      K11 = 5.5-8.2 (MeCN or MeOH/CH2Cl2, I = 0.01 M). The zinc complexes show blue
      fluorescence, both in solution as well as in the solid state, with lambdaem,
      Phif, and tau ranging from 472-504 nm, 0.11-0.60, and 2-9 ns, respectively. The
      nature of the substituents on the salicylaldiminato fragments was found to be the
      main parameter that influences the photophysical properties of the zinc
      complexes. Insights into the electronic nature of the UV-vis transitions were
      obtained with time dependent density functional theory (TD-DFT) calculations.

PMID- 29644368
TI  - Antinutritional factors and hypocholesterolemic effect of wild apricot kernel
      (Prunus armeniaca L.) as affected by detoxification.
AB  - The present investigation was aimed to study the effect of detoxification on the
      nutrients and antinutrients of wild apricot kernel followed by its
      hypocholesterolemic effect in male Wistar albino rats. The results revealed a non
      significant (p > 0.05) effect of detoxification on the proximate composition
      except total carbohydrates and protein content. However, detoxification led to a
      significant (p < 0.05) decrease in l-ascorbic acid (76.82%), beta-carotene
      (25.90%), dietary fiber constituents (10.51-28.92%), minerals (4.76-31.08%) and
      antinutritional factors (23.92-77.05%) (phenolics, tannins, trypsin inhibitor
      activity, saponins, phytic acid, alkaloids, flavonoids, oxalates) along with the
      complete removal (100%) of bitter and potentially toxic hydrocyanic acid (HCN).
      The quality parameters of kernel oil indicated no adverse effects of
      detoxification on free fatty acids, lipase activity, acid value and peroxide
      value, which remained well below the maximum permissible limit. Blood lipid
      profile demonstrated that the detoxified apricot kernel group exhibited
      significantly (p < 0.05) increased levels of HDL-cholesterol (48.79%) and
      triglycerides (15.09%), and decreased levels of total blood cholesterol (6.99%),
      LDL-C (22.95%) and VLDL-C (7.90%) compared to that of the raw (untreated) kernel
      group. Overall, it can be concluded that wild apricot kernel flour could be
      detoxified efficiently by employing a simple, safe, domestic and cost-effective
      method, which further has the potential for formulating protein supplements and
      value-added food products.

PMID- 29644370
TI  - Electrospun ZrO2 nanofibers: precursor controlled mesopore ordering and evolution
      of garland-like nanocrystal arrays.
AB  - We observed that the hydrolysis-condensation reaction of precursors makes a
      significant difference in constructing ordered mesopores in electrospun ZrO2
      nanofibers. Transmission-SAXS studies confirm the generation of uniform clusters
      of size ~1.44 nm in the ZrOCl2.8H2O (inorganic salt) derived sol due to its
      relatively slow hydrolysis-condensation process. These initial -Zr-O-Zr- clusters
      acted as building blocks to form uniform 3D ordered cubic (Pm3[combining
      macron]m) mesopores in the presence of Pluronic F127 surfactant. In contrast, the
      commonly used Zr-alkoxide (zirconium n-propoxide) precursor, which is highly
      hydrolysable even after the use of a controlling agent, generates larger clusters
      with broad size distributions due to the uncontrolled hydrolysis-condensation of
      alkoxy groups. Accordingly, in the presence of F127, the alkoxide derived sol
      yielded disordered mesopores in the resultant fibers. XRD under dynamic heating
      conditions (up to 900  degrees C) and the corresponding TEM studies of the
      ZrOCl2.8H2O derived nanofibers confirmed the retention of mesopores even in the
      extremely thin nanofibers (diameter ~15-25 nm) after the amorphous to crystal
      phase transformation (cubic/tetragonal). An interesting morphological
      transformation has been observed in the nanofibers at 900  degrees C where the
      fibers have been uniformly segmented by distinct single nanocrystals (width ~15
      65 nm) with mesopores. Further heat-treatment at 1100  degrees C made these
      segmented nanofibers nonporous, and a garland-like appearance with monoclinic
      nanocrystal arrays was formed.

PMID- 29644371
TI  - Ferumoxytol of ultrahigh magnetization produced by hydrocooling and magnetically
      internal heating co-precipitation.
AB  - Ferumoxytol, which is originally intended for MRI and anemia treatment, is
      currently the only inorganic nanodrug approved by FDA for clinical application in
      vivo. Common ferumoxytol seems incapable of meeting the requirements for diverse
      applications. Thus, the development of a novel strategy based on co-precipitation
      to produce ferumoxytol with high quality is an imminent task. Herein, we proposed
      a physically assisted strategy, namely hydrocooling and magnetically internal
      heating co-precipitation, to optimize the properties of ferumoxytol and thus
      significantly enhance its magnetic performance. Magnetization of the newly
      developed ferumoxytol can reach 104-105 emu g-1 Fe, which is the highest value
      among the reported results. It has been found that the crystalline structures of
      the newly developed ferumoxytol have been greatly improved on the basis of
      pharmaceutical quality criteria.

PMID- 29644372
TI  - Fullerene size controls the selective complexation of [11]CPP with pristine and
      endohedral fullerenes.
AB  - The ability of the carbon nanoring [11]cycloparaphenylene ([11]CPP) for
      coordinating fullerenes has been tested using a series of hosts, including the
      pristine fullerenes C60, C70, C76 and C78, the clusterfullerene Sc3N@C80,
      monometallic endofullerenes Y@C82 and Tm@C82, and dimetallic endofullerenes
      Y2@C82 and Lu2@C82. A systematic theoretical study employing dispersion corrected
      density functional methods has been carried out in order to explore the
      characteristics of the complexes and the strength of the interaction. Depending
      on the dimer, complexation energies span from around -36 kcal mol-1 with C60 to 
      53 kcal mol-1 with the C82 derivatives. Dispersion is the main stabilizing
      contribution in these dimers, so the molecules arrange to maximize the number of
      close interatomic contacts. Since most fullerenes can properly fill the cavity of
      the nanoring the stability of the complexes is pretty similar, with the exception
      of the smallest fullerenes. The complexes with endohedral fullerenes show similar
      stabilities in all cases studied, with no noticeable dependence on the nature of
      the endohedral species. The results obtained suggest that fullerenes larger than
      C76 could be selectively encapsulated by [11]CPP compared to smaller fullerenes.

PMID- 29644373
TI  - Photochromism and the fluorescence properties of bisbenzothienylethene and
      S,S,S',S'-tetraoxide derivatives with dual conjugated fluorescent groups on their
      side chains.
AB  - Two photochromic bisbenzothienylethenes with two fluorescent (4-((2,5
      bis(dodecyloxy)-4-(phenylethynyl)phenyl)ethynyl)phenyl) units and their disulfone
      derivatives were synthesized, and their photochromic and fluorescence properties
      were examined. Bisbenzothienylethenes showed photochromism and turn-off type
      fluorescence by UV-light irradiation, while their disulfone derivatives showed
      turn-on type fluorescence and the one-way isomerization to the closed form.

PMID- 29644374
TI  - Application of 3D hierarchical monoclinic-type structural Sb-doped WO3 towards
      NO2 gas detection at low temperature.
AB  - Currently, the development of semiconducting metal oxide (SMO)-based gas sensors
      with innovative modification and three-dimensional (3D) structural designs has
      become a significant scientific interest due to their potential for addressing
      key technological challenges. Herein, gas sensing devices based on the 3D
      hierarchical monoclinic-type structural Sb-doped WO3 (HMSW) gas sensing material
      were successfully constructed by ordered assembly of urchin-like monoclinic-type
      structural (P2/m) Sb-doped WO2.72 (W18O49) (UMSW) nanocrystals and nanowires. The
      crystalline microstructure, composition, morphological characteristics, and
      possible growth mechanisms were systematically investigated. The results of the
      gas sensor measurements, performed simultaneously on multiple samples, indicated
      that the 3D HMSW material has superior sensitivity (S = 122) and high selectivity
      to ppm-level NO2 at 30  degrees C with a significantly larger response than the
      best-reported values from other WO3-based gas sensors fabricated so far. All the
      results clearly demonstrate that the combined effects of abundant structural
      defects derived from Sb doping modification, reduced band gap, and 3D
      hierarchical microstructure synergistically play a key role in the NO2 gas
      sensing performance. Such excellent gas sensing performance foresees the great
      potential application of 3D hierarchical structural WO3-based sensors for fast
      and effective detection of toxic gases that can aid in human health and public
      safety.

PMID- 29644375
TI  - Ultrasmall fluorescent nanoparticles derived from roast duck: their
      physicochemical characteristics and interaction with human serum albumin.
AB  - Fluorescent nanoparticles (FNPs) produced from roast meat have drawn widespread
      attention due to their potential hazards to human health. In this paper, the
      presence of ultrasmall FNPs in roast duck and their interaction with human serum
      albumin (HSA) were reported. The processing-induced FNPs have an average size of
      1.3 nm with a relative fluorescence quantum yield of 4.4%. X-ray photoelectron
      spectroscopy showed that the FNPs are composed of carbon (70.48%), nitrogen
      (6.25%), oxygen (22.17%) and sulfur (1.11%), with hydroxyl, carboxyl and amino
      groups present on their surface. The presence of FNPs could cause fluorescence
      quenching of HSA, which was ascribed to the static quenching mechanism via the
      electrostatic interaction as analyzed by isothermal titration calorimetry. The
      alpha-helix contents of HSA decreased after the addition of FNPs, demonstrating
      that these processing-induced FNPs could cause structural alteration of HSA.
      These results provided insights into the formation of nanoparticles in roast
      duck, and offered important information about the binding mechanism of these
      nanoparticles with HSA, which may have physiological implications.

PMID- 29644376
TI  - Sr5Os3O13: a mixed valence osmium(v,vi) layered perovskite variant exhibiting
      temperature dependent charge distribution.
AB  - New Sr5Os3O13, as synthesized from binary constituents, exhibits several uncommon
      features. Its crystal structure is dominated by quasi-2D poly-oxoanions that
      correspond to unprecedented cutouts of the perovskite type of structure, where
      corner sharing (OsO6) octahedra aggregate to form terraced slabs. The Os5+/Os6+
      mixed valence oxide displays a particular charge ordering scheme. One osmium atom
      (Os1) per formula unit is in the valence state of 5+ in the whole temperature
      range studied, while the two remaining sites (Os2A and Os2B) show full charge
      disorder at high temperatures, resulting in an average charge of 5.5+. The
      latter, however, apparently undergo a process of continuous charge ordering at
      cooling. Full charge order appears to be established concomitantly with a phase
      transition to an antiferromagnetically ordered state at T(Neel) = 170 K. This
      kind of temperature dependent continuous charge ordering is reflected by
      structural changes with temperature as well as by changes in paramagnetic
      response above T(Neel). Disentangling the intimate interplay between magnetic and
      charge ordering degrees of freedom will require applying sophisticated
      spectroscopy and (neutron) diffraction techniques.

PMID- 29644377
TI  - Scaling up rehabilitation - Towards an international policy agenda.
AB  - No Abstract (Guest Editorial).

PMID- 29644378
TI  - A simple and ultrasensitive fluorescence assay for single-nucleotide
      polymorphism.
AB  - In this report, a simple, label-free and highly efficient nucleic acid
      amplification technique is developed for ultrasensitive detection of single
      nucleotide polymorphism (SNP). Briefly, a designed padlock probe is first
      circularized by a DNA ligase when it perfectly complements to a mutant gene.
      Then, the mutant gene functions as a primer to initiate branched rolling circle
      amplification reaction (BRCA), generating a large number of branched DNA strands
      and a lot of pyrophosphate molecules which is equivalent to the number of
      nucleotides consumed. With the addition of a terpyridine-Zn(II) complex,
      pyrophosphate molecules can be sensitively detected owing to the formation of a
      fluorescent terpyridine-Zn(II)-pyrophosphate complex. The fluorescence intensity
      is directly associated with the content of the mutant gene in a sample solution.
      On the other hand, the circulation of the padlock probe is prohibited when it
      hybridizes with the wild-type gene. In this assay, the accumulative nature of the
      BRCA process produces a detection limit of 0.1 pM and an excellent selectivity
      factor of 1000 toward SNP. As little as 0.1% mutant in the wild-type gene can be
      successfully detected. The simple procedure, high sensitivity, and high
      selectivity of this assay offer a potentially viable alternative for routine SNP
      analysis. Graphical abstract A simple and label-free fluorescence assay for SNP
      detection by coupling BRCA with selective fluorescence detection of pyrophosphate
      using the terpyridine-Zn(II) complex.

PMID- 29644379
TI  - Cyanotrophic and arsenic oxidizing activities of Pseudomonas mendocina P6115
      isolated from mine tailings containing high cyanide concentration.
AB  - Mine tailings and wastewater generate man-made environments with several
      selective pressures, including the presence of heavy metals, arsenic and high
      cyanide concentrations, but severe nutritional limitations. Some oligotrophic and
      pioneer bacteria can colonise and grow in mine wastes containing a low
      concentration of organic matter and combined nitrogen sources. In this study,
      Pseudomonas mendocina P6115 was isolated from mine tailings in Durango, Mexico,
      and identified through a phylogenetic approach of 16S rRNA, gyrB, rpoB, and rpoD
      genes. Cell growth, cyanide consumption, and ammonia production kinetics in a
      medium with cyanide as sole nitrogen source showed that at the beginning, the
      strain grew assimilating cyanide, when cyanide was removed, ammonium was produced
      and accumulated in the culture medium. However, no clear stoichiometric
      relationship between both nitrogen sources was observed. Also, cyanide complexes
      were assimilated as nitrogen sources. Other phenotypic tasks that contribute to
      the strain's adaptation to a mine tailing environment included siderophores
      production in media with moderate amounts of heavy metals, arsenite and arsenate
      tolerance, and the capacity of oxidizing arsenite. P. mendocina P6115 harbours
      cioA/cioB and aoxB genes encoding for a cyanide-insensitive oxidase and an
      arsenite oxidase, respectively. This is the first report where P. mendocina is
      described as a cyanotrophic and arsenic oxidizing species. Genotypic and
      phenotypic tasks of P. mendocina P6115 autochthonous from mine wastes are
      potentially relevant for biological treatment of residues contaminated with
      cyanide and arsenic.

PMID- 29644381
TI  - Autologous rectus fascia sling placement in the management of female stress
      urinary incontinence.
AB  - INTRODUCTION AND HYPOTHESIS: Autologous pubovaginal sling placement remains a
      treatment option in index patients, given high, long-term success rates. This
      video reviews the technical considerations for performing an autologous rectus
      fascia sling. METHODS: The patient is a 47-year-old woman with stress urinary
      incontinence (SUI) refractory to conservative management. First, a 10-cm rectus
      fascial segment is harvested and prepped with placement of nonabsorbable stay
      sutures for later sling passage. Then, an inverted U-shaped incision is made in
      the anterior vaginal wall based on the bladder neck, and perforation of the
      endopelvic fascia is performed. Following passage of the sling in the retropubic
      space, it is secured to periurethral tissue. Cystoscopy is then used to evaluate
      for bladder perforation and to confirm sling tensioning. RESULTS: The patient was
      discharged on the same day of surgery with a suprapubic tube in place, which was
      removed on postoperative day 7 after passing a capping trial. At 6 weeks' follow
      up, the patient had complete resolution of SUI, with no de novo urgency symptoms,
      and could empty her bladder to completion. CONCLUSION: Autologous pubovaginal
      sling placement remains an effective treatment option for the management of
      female SUI. This video highlights important technical considerations for this
      procedure.

PMID- 29644380
TI  - Entry into the anterior cul-de-sac during vaginal hysterectomy.
AB  - INTRODUCTION AND HYPOTHESIS: We present a video reviewing the key steps involved
      in safe anterior cul-de-sac entry during vaginal hysterectomy, including tips for
      troubleshooting difficult cases such as: uterine procidentia, cervical
      elongation, and multiple prior cesarean sections. METHODS: Anterior cul-de-sac
      entry is a critical step in performing a vaginal hysterectomy. In this video, we
      review our approach to anterior entry in patients with normal anatomy, followed
      by a discussion of techniques that may be useful in cases with challenging
      anatomy. To start, we drain the bladder, set up exposure with Deaver retractors,
      and make a circumferential incision at the cervicovaginal junction. In cases with
      normal anatomy, using sharp, followed by broad blunt finger dissection, the
      vesicocervical space is opened, and the peritoneal reflection is identified and
      sharply entered. If this is not possible, additional techniques such cystoscopic
      bladder illumination, posterior entry first, securing pedicles with
      extraperitoneal ties, or additional sharp dissection may be utilized. With all
      techniques, proper intraperitoneal entry should be verified by the visualization
      of small bowel or fat. CONCLUSION: This video reviews technical considerations
      for anterior cul-de-sac entry during vaginal hysterectomy in patients with normal
      anatomy and provides tips for troubleshooting challenging cases.

PMID- 29644382
TI  - Prolapse reduction deteriorates the urethral closure mechanism.
AB  - INTRODUCTION AND HYPOTHESIS: Pelvic organ prolapse (POP) reduction is often
      performed in the preoperative assessment of women before POP surgery. Using
      urethral pressure reflectometry (UPR), we sought to investigate how POP reduction
      affects the urethral closure mechanism. METHODS: Women with anterior or posterior
      vaginal wall prolapse stage >=II with and without POP reduction were examined
      with a speculum. We performed prolapse staging according to the Pelvic Organ
      Prolapse Quantification system, UPR measurements at rest and during squeezing,
      and standardized stress tests with 300 ml saline. All examinations were repeated
      after insertion of a speculum. RESULTS: We included 38 women: 22 with anterior
      and 16 with posterior vaginal wall prolapse POP-Q stage  >=II. During POP
      reduction, resting and squeezing urethral pressures decreased by 2.5 cmH2O (p =
      0.007) and 5.1 cmH2O (p < 0.0001), respectively, in all women. During POP
      reduction, the number of positive stress tests increased from four (18%) to eight
      (36%) in women with anterior vaginal wall prolapse and from one (6%) to nine
      (56%) in women with posterior vaginal wall prolapse. CONCLUSIONS: POP reduction
      decreases urethral pressure, especially during squeezing, and consequently
      increases the number of positive stress tests. The test itself artificially
      deteriorates the urethral closure mechanism.

PMID- 29644383
TI  - Optimizing resident operative self-confidence through competency-based surgical
      education modules: are we there yet?
AB  - INTRODUCTION AND HYPOTHESIS: Self-confidence is the belief in one's ability to
      perform and can be enhanced by training. Surgical education should aim to
      optimize trainee confidence. We designed three procedure-specific competency
      based modules to teach vaginal hysterectomy (VH), anterior (AR) and posterior
      repair (PR) to novice gynecology residents. We hypothesized each module would
      improve self-confidence and satisfaction during index procedure performance in
      the operating room. METHODS: This was an ancillary analysis of a larger
      randomized-controlled trial of gynecologic educational interventions. Residents
      at three Canadian universities were included if they had previously performed
      fewer than five index procedures independently. Intervention residents received
      educational modules; controls engaged in self-directed learning. All residents
      performed one or more of the three surgeries and filled out a validated Self
      Confidence Scale and a Satisfaction Scale. Scores were compared between groups.
      Correlations were sought between self-confidence and various variables. RESULTS:
      Forty-six residents at three Canadian universities were randomized (21
      intervention, 25 control). Most residents had never performed the index
      procedure. Overall, self-confidence was significantly higher (p = 0.021) in the
      intervention group for VH, but not for AR and PR (p = 0.94 and p = 0.12,
      respectively). Compared with controls, self-confidence was also significantly
      higher in intervention residents who had never performed VH (p = 0.026) or PR (p
      = 0.027) and in first and second year intervention residents. There was a
      positive correlation between self-confidence and satisfaction. CONCLUSIONS:
      Surgical modules improved self-confidence preferentially in the most junior
      residents and for more complicated procedures. The wide self-confidence ranges
      observed suggest that optimization should be an important goal for surgical
      educators.

PMID- 29644384
TI  - Efficacy of pelvic floor muscle training in women with overactive bladder
      syndrome: a systematic review.
AB  - INTRODUCTION AND HYPOTHESIS: Our objective was to evaluate the effectiveness of
      pelvic floor muscle training (PFMT) in reducing overactive bladder (OAB) symptoms
      in women. METHODS: Searches were performed at MEDLINE, PubMed, Physiotherapy
      Evidence Database (PEDro), Scielo, and Central Cochrane Library PubMed until
      January 2017. Controlled trials were researched by two independent reviewers.
      Eligible studies were restricted to random and controlled clinical trials that
      investigated the effectiveness of PFMT in decreasing OAB symptoms. Qualitative
      methodology was evaluated using the PEDro scale. Data was analyzed and
      interpreted qualitatively. RESULTS: The final search retrieved eight studies (n =
      1161 women with urgency symptoms), which were published between 2002 and 2016.
      The methodological scores varied between 4 and 7 in the PEDro scale. PFMT, with
      the objective of controlling urgent micturition, demonstrated improvements in
      quality of life in women with OAB. Most data in this revision came from small- to
      moderate-sized trials, with different and inconsistent outcome measures, which
      could have impacted the end results. CONCLUSIONS: The literature regarding the
      effectiveness of PFMT in OAB remains heterogeneous and inconclusive.

PMID- 29644385
TI  - Postoperative alpha angle not associated with patient-centered midterm outcomes
      following hip arthroscopy for FAI.
AB  - PURPOSE: The most commonly used parameter for defining cam-type femoroacetabular
      impingement(FAI) has been the alpha angle. The purpose of this study was to
      determine if patient-reported outcomes 5 years following hip arthroscopy for FAI
      were associated with postoperative alpha angle. We hypothesized that patient
      reported outcomes would not be influenced by postoperative alpha angle in
      patients with FAI. METHODS: 230 patients had primary hip arthroscopy for FAI and
      chondrolabral dysfunction. The median age was 40 years (range 18-69). All
      patients had preoperative and 1 day postoperative alpha angles recorded. At
      minimum 5 years following arthroscopy, all patients completed an online
      questionnaire that included the modified Harris Hip score(MHHS), WOMAC, HOS ADL,
      HOS Sport, SF12 and patient satisfaction. This study was IRB approved. Patients
      were grouped into two, based on their postoperative alpha angle: <55 degrees  (n
      = 158) and >= 55 degrees  (n = 56). RESULTS: The median preoperative alpha angle
      was 72 degrees  (range 50 degrees -105 degrees ) and the median postoperative
      alpha angle was 45 degrees  (range 30 degrees -100 degrees ). The postoperative
      alpha angle did not correlate with any outcome measure. The median preoperative
      alpha angle in the < 55 degrees  group was 71 degrees  and in >= 55 degrees 
      group the median was 74 degrees  (p = 0.044). The median follow-up was 5.1 years
      (range 5-7). The median mHHS was 85 (range 47-100) in the < 55 degrees  and 85
      (range 54-100) in the >= 55 degrees  group (n.s); WOMAC was 5 (range 0-73) in the
      < 55 degrees  and 4.5 (range 1-57) in the >= 55 degrees  group(n.s); HOS ADL was
      95 (range 31-100) in the < 55 degrees  and 96 (range 50-100) in the >= 55 degrees
      group (n.s); HOS Sport was 88 (range 0-100) in the < 55 degrees  and 88 (range
      13-100) in the >= 55 degrees  group (n.s) Median patient satisfaction was 9
      (range 1-10) in both groups. CONCLUSION: This study shows no statistically
      significant differences between the investigated patient-reported outcome scores
      at a 5 years postoperatively in relation to a correction of the alpha angle to 55
      degrees . While alpha angle has been shown to be an excellent preoperative
      diagnostic tool, the postoperative angle does not correlate with midterm outcomes
      or the development of osteoarthritis based on patient symptoms. The amount of
      osteoplasty should be based on dynamic examination at arthroscopy, and not by
      alpha angle. LEVEL OF EVIDENCE: III Case-control, retrospective comparative
      study.

PMID- 29644386
TI  - Correction to: The WOMAC score can be reliably used to classify patient
      satisfaction after total knee arthroplasty.
AB  - Unfortunately, Fig. 1 in the original article contained incorrect information.
      Hereby, the correct figure is published and we apologise for the inconvenience.

PMID- 29644387
TI  - Personalized cancer vaccines: adjuvants are important, too.
AB  - Therapeutic cancer vaccines have shown limited clinical efficacy so far.
      Nevertheless, in the meantime, our understanding of immune cell function and the
      interactions of immune cells with growing tumors has advanced considerably. We
      are now in a position to invest this knowledge into the design of more powerful
      vaccines and therapy combinations aimed at increasing immunogenicity and
      decreasing tumor-induced immunosuppression. This review focuses essentially on
      peptide-based human vaccines. We will discuss two aspects that are critical for
      increasing their intrinsic immunogenicity: the selection of the antigen(s) to be
      targeted, and the as yet unmet need for strong adjuvants.

PMID- 29644388
TI  - The relation between obesity and depressed mood in a multi-ethnic population. The
      HELIUS study.
AB  - PURPOSE: To examine the association between obesity and depressed mood in a large
      multi-ethnic population and check for consistency in this association across six
      ethnic groups. METHODS: Data of 21,030 persons (18-70 years) were sourced from
      the HELIUS study. Cross-sectional relationships between obesity measures [body
      mass index (kg/m2) and waist circumference (cm)] and depressed mood (PHQ-9 score
      >= 10) were analysed. Consistency of associations was investigated across ethnic
      groups by interaction terms (ethnicity*obesity measures) in basic (age, sex,
      education) and fully (health behaviours and somatic health) adjusted models.
      RESULTS: Obesity was prevalent in all ethnic groups, but varied substantially.
      After sociodemographic adjustment, obesity measures were associated with
      increased odds of depressed mood but this was inconsistent across ethnic groups.
      Obesity (BMI >= 30 or highest waist circumference quartile) was strongly and
      significantly associated with depressed mood in the Dutch [Odds Ratio (OR) =
      1.72; 95% Confidence intervals (CI) 1.24-2.40, and OR = 1.86; 95% CI 1.38-2.50],
      respectively, and African Surinamese (OR = 1.60; 95% CI 1.29-1.98 and OR = 1.59;
      95% CI 1.27-2.00, respectively) but had a weaker, non-significant association in
      other ethnic groups (South-Asian Surinamese, Ghanaian, Moroccan, Turkish groups).
      Adjustment for health behaviours and somatic health had limited effect on this
      pattern. CONCLUSION: Obesity was associated with a higher risk of depressed mood.
      However, ethnic differences were found: the obesity-depressed mood association
      was strong in the Dutch and African Surinamese populations, but not in other
      ethnic groups. Future studies should explore whether differential normative
      values or pathophysiology across ethnic groups explain why the obesity-depression
      association is inconsistent across ethnic groups.

PMID- 29644390
TI  - Evaluation of crown inclination and angulation after orthodontic treatment using
      digital models : Comparison to the prescription of the brackets used.
AB  - PURPOSE: To compare crown inclination and angulation results obtained after
      orthodontic treatment to the Roth prescription. METHODS: The study design was
      based on files and documents obtained from a database of 26 patients who had
      undergone orthodontic treatment using the straight-wire technique and the Roth
      prescription. The crown inclination and angulation were measured using a three
      dimensional (3D) cephalometric module (VistaDent, Dentsply, New York, NY, USA) by
      an orthodontist. A coordinate system (x, y, z) was developed for each tooth that
      used the Andrews plane as a para-axial reference. Descriptive statistical
      analysis provided the mean and standard deviation (SD) of crown inclination and
      angulation obtained after orthodontic treatment, which were compared to the Roth
      prescription. RESULTS: Method reproducibility is an important test to investigate
      the margin of error and to verify the reliability of results. The results at time
      1 (1.6 degrees  +/- 1.1 degrees ) and time 2 (1.7 degrees  +/- 1.2 degrees ) of
      the pilot study were not statistically different (p = 0.99). Maxillary lateral
      and central incisors presented significant differences in crown angulation (p <
      0.05) compared to the Roth prescription. The crown angulation of maxillary second
      premolars with regard to the occlusal plane presented a similar value to the Roth
      prescription. CONCLUSION: Crown inclination and angulation found at the end of
      orthodontic treatment did not match the prescription of the brackets for most
      teeth, as measured using digital models.

PMID- 29644389
TI  - Is there an optimal initial amount of activation for midpalatal suture expansion?
      : A histomorphometric and immunohistochemical study in a rabbit model.
AB  - OBJECTIVE: Accelerated bone-borne expansion protocols on sutural separation and
      sutural bone formation were evaluated via histomorphometry and
      immunohistochemistry to determine the optimal initial activation without
      disruption of bone formation. MATERIALS AND METHODS: Sixteen New Zealand white
      rabbits were randomly divided into four groups. Modified Hyrax expanders were
      placed across the midsagittal sutures and secured with miniscrew implants with
      the following activations: group 1 (control), 0.5 mm expansion/day for 12 days;
      group 2, 1 mm instant expansion followed by 0.5 mm expansion/day for 10 days;
      group 3, 2.5 mm instant expansion followed by 0.5 mm expansion/day for 7 days;
      and group 4, 4 mm instant expansion followed by 0.5 mm expansion/day for 4 days.
      After 6 weeks, sutural expansion and new bone formation were evaluated
      histomorphometrically. Statistical analysis was performed using Kruskal
      Wallis/Mann-Whitney U tests and Spearman's rho correlation (p < 0.05). RESULTS:
      The smallest median sutural separation was observed in group 1 (3.05 mm) and the
      greatest in group 4 (4.57 mm). The lowest and highest amount of bone formation
      were observed in group 4 (55.82%) and in group 3 (66.93%), respectively.
      Immunohistochemical analysis revealed significant differences in median levels of
      alkaline phosphatase and osteopontin expression between all experimental groups.
      The highest level of these proteins was attained in group 3, followed by groups
      2, 1, and 4, respectively. CONCLUSIONS: Sutural appositional bone formation
      corresponded with the amount of initial expansion to a point. When initial
      expansion was increased to 4 mm, sutural bone remodeling was disturbed and new
      bone formation was decreased. The most effective sutural expansion was achieved
      with 2.5 mm initial activation followed by 0.5 mm expansion/day for 7 days.

PMID- 29644392
TI  - Effect of a rest-pause vs. traditional squat on electromyography and lifting
      volume in trained women.
AB  - PURPOSE: Rest-pause (4 s unloaded rest between repetitions) single session
      training effects on lifting volume, and muscle activity via electromyography
      (EMG) are currently vague in the literature and can benefit strength and
      conditioning professionals for resistance training program design. This study
      compared differences in volume lifted and muscle activity between a rest-pause
      vs. traditional protocol. METHODS: Trained females (N = 13) completed both a rest
      pause and traditional squat protocol consisting of four sets to movement failure
      at 80% pretest 1 repetition maximum load with 2-min rest between sets. Total
      volume and muscle activity of the vastus lateralis, vastus medialis, rectus
      femoris, and gluteus maximus were measured on both training days. Differences in
      muscle activity were viewed as a percent change (%?). RESULTS: A paired samples t
      test indicated total volume lifted was higher in the rest-pause compared to the
      traditional protocol (2532 vs. 2036 kg; p < .05). Furthermore, paired samples t
      tests showed muscle activity %? of the gluteus maximus was greater in the
      traditional protocol compared to the rest-pause protocol (p < .05). No other
      muscle activity differences were observed in the remaining muscles. CONCLUSIONS:
      The rest-pause allows for greater volume lifted via increased repetitions
      compared to a traditional protocol in trained women. The rest-pause method may be
      superior to a traditional method of training during a hypertrophy mesocycle,
      where a primary focus is total volume lifted. Furthermore, %? muscle activity in
      the GM will be greater while performing a traditional back squat protocol in
      comparison to a rest-pause.

PMID- 29644391
TI  - Analysis on sarcoglycans expression as markers of septic cardiomyopathy in sepsis
      related death.
AB  - The post-mortem assessment of sepsis-related death can be carry out by many
      methods recently suggested as microbiological and biochemical investigations. In
      these cases, the cause of death is a multiple organ dysfunction due to a
      dysregulated inflammatory response occurring after the failure of infection
      control process. It was highlighted also that the heart can be a target organ in
      sepsis which determines the so-called septic cardiomyopathy characterized by
      myocardial depression. Several mechanisms to explain the pathophysiology of
      septic cardiomyopathy were suggested, but very few studies about the structural
      alterations of cardiac cells responsible for myocardial depression were carried
      out. The aim of this study was to evaluate whether sarcoglycans (SG) were
      involved in septic cardiac damage analyzing their expression in sepsis-related
      deaths and, particularly, if these proteins can be used as markers of septic
      myocardial dysfunction. Cases of septic-related death confirmed by clinical and
      autopsy records were investigated and compared to a control group of traumatic
      deaths. Indirect immunofluorescence analysis was performed to analyze alpha-SG,
      beta-SG, delta-SG, zeta-SG, epsilon-SG, and gamma-SG. Decrease of fluorescence
      staining pattern for all tested sarcoglycans was observed in the septic-related
      deaths compared to normal fluorescence staining pattern of control group. These
      results provide new findings about the myocytes structural alterations due to
      sepsis and suggest that these proteins could be used in forensic assessment of
      septic cardiomyopathy.

PMID- 29644393
TI  - Treatment of carcinoma in situ of the urinary bladder with an alpha-emitter
      immunoconjugate targeting the epidermal growth factor receptor: a pilot study.
AB  - PURPOSE: Patients with carcinoma in situ (CIS) of the bladder refractory to
      bacillus Calmette-Guerin (BCG) treatment are usually treated with cystectomy.
      Therefore, new treatment options with preservation of the urinary bladder are
      needed. The objective of the study was to investigate the feasibility, safety and
      efficacy of a novel targeted alpha-emitter immunotherapy for CIS after BCG
      treatment failure. METHODS: A pilot study was conducted in 12 patients (age range
      64-86 years, ten men, two women) with biopsy-proven CIS of the bladder refractory
      to BCG treatment. The patients were treated intravesically with a single
      instillation (one patient was treated twice) of the alpha-emitter 213Bi coupled
      to an anti-EGFR antibody (366-821 MBq). The primary aims of the study were to
      determine the feasibility of treatment with the 213Bi-immunoconjugate and
      evaluation of adverse effects. Therapeutic efficacy was monitored by histological
      mapping of the urinary bladder 8 weeks after treatment and at different time
      points thereafter. RESULTS: The study proved that intravesical instillation of
      the 213Bi-immunoconjugate targeting EGFR is feasible. No adverse effects were
      observed and all blood and urine parameters determined remained in their normal
      ranges. Therapeutic efficacy was considered satisfactory, in that three of the 12
      patients showed no signs of CIS 44, 30 and 3 months after treatment. CONCLUSION:
      Intravesical instillation of 213Bi-anti-EGFR monoclonal antibody was well
      tolerated and showed therapeutic efficacy. Repeated instillation and/or
      instillation of higher activities of the 213Bi-immunoconjugate might lead to
      better therapeutic outcomes. A phase I clinical trial is planned.

PMID- 29644394
TI  - Genomic analysis reveals secondary glioblastoma after radiotherapy in a subset of
      recurrent medulloblastomas.
AB  - Despite great advances in understanding of molecular pathogenesis and achievement
      of a high cure rate in medulloblastoma, recurrent medulloblastomas are still
      dismal. Additionally, misidentification of secondary malignancies due to
      histological ambiguity leads to misdiagnosis and eventually to inappropriate
      treatment. Nevertheless, the genomic characteristics of recurrent
      medulloblastomas are poorly understood, largely due to a lack of matched primary
      and recurrent tumor tissues. We performed a genomic analysis of recurrent tumors
      from 17 pediatric medulloblastoma patients. Whole transcriptome sequencing
      revealed that a subset of recurrent tumors initially diagnosed as locally
      recurrent medulloblastomas are secondary glioblastomas after radiotherapy,
      showing high similarity to the non-G-CIMP proneural subtype of glioblastoma.
      Further analysis, including whole exome sequencing, revealed missense mutations
      or complex gene fusion events in PDGFRA with augmented expression in the
      secondary glioblastomas after radiotherapy, implicating PDGFRA as a putative
      driver in the development of secondary glioblastomas after treatment exposure.
      This result provides insight into the possible application of PDGFRA-targeted
      therapy in these second malignancies. Furthermore, genomic alterations of TP53
      including 17p loss or germline/somatic mutations were also found in most of the
      secondary glioblastomas after radiotherapy, indicating a crucial role of TP53
      alteration in the process. On the other hand, analysis of recurrent
      medulloblastomas revealed that the most prevalent alterations are the loss of 17p
      region including TP53 and gain of 7q region containing EZH2 which already exist
      in primary tumors. The 7q gain events are frequently accompanied by high
      expression levels of EZH2 in both primary and recurrent medulloblastomas, which
      provides a clue to a new therapeutic target to prevent recurrence. Considering
      the fact that it is often challenging to differentiate between recurrent
      medulloblastomas and secondary glioblastomas after radiotherapy, our findings
      have major clinical implications both for correct diagnosis and for potential
      therapeutic interventions in these devastating diseases.

PMID- 29644395
TI  - Metabolic phenotyping of malnutrition during the first 1000 days of life.
AB  - Nutritional restrictions during the first 1000 days of life can impair or delay
      the physical and cognitive development of the individual and have long-term
      consequences for their health. Metabolic phenotyping (metabolomics/metabonomics)
      simultaneously measures a diverse range of low molecular weight metabolites in a
      sample providing a comprehensive assessment of the individual's biochemical
      status. There are a growing number of studies applying such approaches to
      characterize the metabolic derangements induced by various forms of early-life
      malnutrition. This includes acute and chronic undernutrition and specific
      micronutrient deficiencies. Collectively, these studies highlight the diverse and
      dynamic metabolic disruptions resulting from various forms of nutritional
      deficiencies. Perturbations were observed in many pathways including those
      involved in energy, amino acid, and bile acid metabolism, the metabolic
      interactions between the gut microbiota and the host, and changes in metabolites
      associated with gut health. The information gleaned from such studies provides
      novel insights into the mechanisms linking malnutrition with developmental
      impairments and assists in the elucidation of candidate biomarkers to identify
      individuals at risk of developmental shortfalls. As the metabolic profile
      represents a snapshot of the biochemical status of an individual at a given time,
      there is great potential to use this information to tailor interventional
      strategies specifically to the metabolic needs of the individual.

PMID- 29644396
TI  - Correction to: Pupillometry as an indicator of L-DOPA dosages in Parkinson's
      disease patients.
AB  - Unfortunately, original article has been published without acknowledgement
      section.

PMID- 29644397
TI  - COQ2 variants in Parkinson's disease and multiple system atrophy.
AB  - Coenzyme Q2, polyprenyltransferase (COQ2) variants have been reported to be
      associated with multiple system atrophy (MSA). However, the relationship between
      COQ2 variants and familial Parkinson's disease (PD) remains unclear. We
      investigated the frequency of COQ2 variants and clinical symptoms among familial
      PD and MSA. We screened COQ2 using the Sanger method in 123 patients with
      familial PD, 52 patients with sporadic PD, and 39 patients with clinically
      diagnosed MSA. Clinical information was collected from medical records for the
      patients with COQ2 variants. Allele frequencies of detected rare non-synonymous
      variants were compared by public database of the Exome Aggregation Consortium
      (ExAC) and Japanese genetic variation database, using Fisher's exact test. We
      detected two probands with rare variants in COQ2, the p.P157S from Family A,
      whose patient was clinically diagnosed as having juvenile PD, and the p.H15
      N/p.G331S from Family B, whose patients shared common symptoms of PD.
      Furthermore, in an association study comparing these familial PD and MSA cases
      with a public variant database, eight non synonymous variants were detected in
      COQ2. Three of these were very rare variants, namely, p.P157S, p.L261Qfs*4, and
      p.G331S, and one variant, p.G21S, was found to show a significant association
      with familial PD. COQ2 variants rarely may associate with the disease onset of
      familial PD. Our findings contribute to an understanding of COQ2 variants in
      neurodegenerative disorders.

PMID- 29644398
TI  - Stent placement in patients with acute subarachnoid haemorrhage: when is it
      justified?
AB  - PURPOSE: Endovascular stents are widely used for the elective treatment of
      cerebral aneurysms. Acute stenting is performed in the management of dissections,
      pseudo-aneurysms, broad-based aneurysms or as a 'bail out' measure after coil
      migration. The purpose of this study is to review the safety of using stents in
      acute subarachnoid haemorrhage. METHODS: The stent registry of our institution
      was reviewed for procedures in patients with acute subarachnoid haemorrhage.
      Imaging studies were reviewed on the hospital's PACS system and the patients'
      notes were retrieved to assess complications and clinical outcomes. Procedures
      were analysed according to the type of stent, treatment indication, antiplatelet
      regime, complications and outcomes. RESULTS: Between 2008 and 2016, 51 stents
      were placed during 50 stenting procedures in 49 patients with acute subarachnoid
      haemorrhage. This included 24 patients with saccular aneurysms, 10 with blister
      aneurysms, 10 dissections and five fusiform aneurysms. Stents were deployed in
      'bail out' situations on eight occasions. In six cases, flow-diverting stents
      were used. Eighteen patients (37%) in the cohort suffered a stroke. Nine patients
      (18%) suffered persistent clinical deficits as a result of the stenting
      procedure, all but one of which occurred within 24 h. Two patients had a
      transient ischaemic episode, and there was evidence of asymptomatic ischaemia on
      imaging in four cases (8%). Five patients died, three (6%) as a result of
      procedural complications. Twelve patients (25%) required a further embolisation
      procedure. CONCLUSION: The use of stents in acute subarachnoid haemorrhage incurs
      a considerable complication risk and should be reserved for exceptional
      circumstances.

PMID- 29644399
TI  - High-resolution MRI of the inner ear enables syndrome differentiation and
      specific treatment of cerebellar downbeat nystagmus and secondary endolymphatic
      hydrops in a postoperative ELST patient.

PMID- 29644400
TI  - [Erratum to: Hot topic: management of delirium].

PMID- 29644401
TI  - [Skill retention using extraglottic airways in out-of-hospital emergencies:
      efficacy and long-term results of simulator-based medical education : A
      prospective follow-up study].
AB  - OBJECTIVE: For emergency medicine personnel (EMP), there is little evidence
      concerning the adequate timing for refresher courses to maintain routine in the
      application of extraglottic airways. The aim of this study was to evaluate the
      efficacy and long-term results of a simulator-based education concept teaching
      the basic airway management skills with extraglottic airways for EMP and also to
      draw conclusions concerning the adequate time interval for refresher courses.
      METHODS: By use of an explorative, prospective simulator-study with nonphysician
      EMP, airway management skills using the Larynxmaske Supreme(r) (LMA-S) after an
      introduction lecture were examined. The application of an endotracheal tube (ETT)
      served as control. Time for preparation of the airway devices, insertion success,
      and resulting apnea time were assessed immediately after the first introduction
      lecture (t1) and unannounced 9-12 months thereafter (t2). RESULTS: Comparison of
      the times for preparation of the LMA-S at t1 and t2 demonstrated similar results.
      After the introduction lecture, all paramedics were able to insert the LMA-S
      successfully after maximal 2 attempts; 9-12 months later success rates with the
      LMA-S were unchanged. Apnea time during airway management was shorter with the
      LMA-S compared to the ETT (p < 0.01). Times needed for preparation of the airway
      devices were similar. CONCLUSION: The results of this simulator study indicate
      that a standardized introduction lecture is appropriate to ensure long-lasting
      procedural skills up to 12 months, so that subsequent refresher courses in basic
      airway management with the LMA-S once a year may be adequate. A simulator-based
      education in basic airway management skills with extraglottic airways is
      recommended for facilitation of further clinical education according to the
      current guidelines.

PMID- 29644402
TI  - [A case of sole supportive care of severe neuroparalytic foodborne botulism due
      to homemade pesto].
AB  - In this article, a case of severe foodborne botulism in a 78-year-old man due to
      homemade pesto is presented. His initial symptoms were gastrointestinal problems.
      Later he suffered of cranial nerve palsies, muscle weakness of the upper
      extremities and respiratory failure, so he had to be admitted to the intensive
      care unit for mechanical ventilation. The botulism was confirmed by serology and
      culture. Because of spontaneously improving neurological deficits, we decided not
      to treat with the botulism antitoxin and the patient had complete clinical
      remission.

PMID- 29644403
TI  - The putative pectin methylesterase gene, BcMF23a, is required for microspore
      development and pollen tube growth in Brassica campestris.
AB  - KEY MESSAGE: BcMF23a contributes to pollen wall development via influencing
      intine construction, which, in turn, influences pollen tube growth. Pollen wall,
      the morphological out face of pollen, surrounds male gametophyte and plays an
      important role in plant reproduction. Pectin methylesterases (PMEs) are involved
      in pollen wall construction by de-esterifying pectin of the intine. In this
      study, the function of a putative pectin methylesterase gene, Brassica campestris
      Male Fertility 23a (BcMF23a), was investigated. Knockdown of BcMF23a by
      artificial microRNA (amiRNA) technology resulted in abnormal pollen intine
      formation outside of the germinal furrows at the binucleate stage. At the
      trinucleate stage, 20.69% of pollen possessed the degradation of nuclei,
      cytoplasm and the intine, resulting in shrunken pollen, whereas the remaining
      75.86% were wall-disrupted with degrading cytoplasm and broken exine inside the
      germinal furrows. In addition, pollen abortion in transgenic plants caused
      germination percentage reduction by 19% in vitro and pollen tube growth
      disruption in natural stigma in vivo. Taken together, BcMF23a is involved in
      pollen development and pollen tube growth, possibly via participating in intine
      construction. This study may contribute towards understanding the function of
      pollen-specific PMEs and the molecular regulatory network of pollen wall
      development.

PMID- 29644406
TI  - The Wessex modified Richmond Sedation Scale as a novel tool for monitoring
      patients at risk of malignant MCA syndrome.
AB  - BACKGROUND: The Wessex Modified Richmond Sedation Scale (WMRSS) has been
      developed with the aim of improving the early identification of patients
      requiring decompressive hemicraniectomy for malignant middle cerebral artery
      syndrome (MMS). The objective of this study was to evaluate the WMRSS against the
      Glasgow Coma Scale (GCS). METHODS: A retrospective study was conducted of
      patients admitted to our unit for observation of MMS. Data were obtained on WMRSS
      and GCS recordings from admission up to 120-h post-ictus. Patients' meeting
      inclusion criteria were recommended for theatre based on subsequent
      deteriorations in consciousness on either WMRSS or GCS from a 6-h post-stroke
      baseline, after ruling out non-neurological causes. RESULTS: Approximately, 60%
      of those eligible for monitoring were not recommended for theatre, and none died;
      however, these patients continued to demonstrate some variability in recorded
      conscious level. Patients requiring surgical intervention showed earlier drops in
      WMRSS compared to GCS. Neither the GCS nor the WMRSS on admission predicted the
      subsequent need for decompressive surgery. There was no increase in mortality
      with the introduction of WMRSS. CONCLUSIONS: WMRSS adds value to monitoring MMS
      by indicating need for surgery prior to GCS. Early reduction in consciousness may
      not be sufficient for proceeding to surgical intervention, but subsequent
      reduction in consciousness may be a more appropriate criterion for surgery.

PMID- 29644405
TI  - Abnormalities in Left Ventricular Rotation Are Inherent in Young Children with
      Repaired Tetralogy of Fallot and Are Independent of Right Ventricular Dilation.
AB  - Left ventricular (LV) dysfunction is a risk factor for adverse outcomes in older
      children and adults with repaired Tetralogy of Fallot (rToF). Pulmonary
      regurgitation (PR), right ventricular (RV) dilation, and dysfunction have been
      shown to result in abnormal LV myocardial mechanics and dysfunction. The aim of
      our study was to evaluate LV rotational mechanics, especially apical rotation in
      young children with rToF with and without RV dilation. This is a retrospective,
      single center study in 28 asymptomatic young children with rToF (16 with RV
      dilation; 12 without RV dilation); 29 age-matched normal controls. RV and LV
      systolic and diastolic function was studied using conventional two-dimensional
      echocardiography (2DE) and speckle tracking echocardiography (STE). Rotational
      mechanics studied included basal and apical rotation (BR, AR), peak twist
      (calculated by difference between the apical and basal rotation), twist rate
      (TR), and untwist rate (UnTR). The mean age of the cohort was 4.7 years (+/-
      2.3). Abnormal AR, BR, TR, and UnTR were noted in patients with rToF. The
      abnormalities were significant in magnitude as well as the direction of rotation;
      more pronounced in the absence of RV dilation. LV systolic and diastolic
      dysfunction as evidenced by abnormal AR and degree of untwist is inherent in rToF
      and not associated with RV dilation in rToF children. Abnormal BR may reflect a
      lack of maturation to adult type of rotational mechanics. Further longitudinal
      studies are required to study the progression of these abnormalities and their
      correlation with clinical outcomes.

PMID- 29644407
TI  - Different Recovery Processes of Soil Ammonia Oxidizers from Flooding Disturbance.
AB  - Understanding how microorganisms respond to environmental disturbance is one of
      the key focuses in microbial ecology. Ammonia-oxidizing bacteria (AOB) and
      archaea (AOA) are responsible for ammonia oxidation which is a crucial step in
      the nitrogen cycle. Although the physiology, distribution, and activity of AOA
      and AOB in soil have been extensively investigated, their recovery from a natural
      disturbance remains largely unknown. To assess the recovery capacities, including
      resistance and resilience, of AOA and AOB, soil samples were taken from a
      reservoir riparian zone which experienced periodically water flooding. The
      samples were classified into three groups (flooding, recovery, and control) for a
      high-throughput sequencing and quantitative PCR analysis. We used a relative
      quantitative index of both the resistance (RS) and resilience (RL) to assess the
      variation of gene abundance, alpha-diversity, and community composition. The AOA
      generally demonstrated a better recovery capability after the flooding
      disturbance compared to AOB. In particular, AOA were more resilient after the
      flooding disturbance. Taxa within the AOA and AOB showed different RS and RL
      values, with the most abundant taxa showing in general the highest RS indices.
      Soil NH4+ and Fe2+/Fe3+ were the main variables controlling the key taxa of AOA
      and AOB and probably influenced the resistance and resilience properties of AOA
      and AOB communities. The distinct mechanisms of AOA and AOB in maintaining
      community stability against the flooding disturbance might be linked to the
      different life-history strategies: the AOA community was more likely to represent
      r-strategists in contrast to the AOB community following a K-life strategy. Our
      results indicated that the AOA may play a vital role in ammonia oxidation in a
      fluctuating habitat and contribute to the stability of riparian ecosystem.

PMID- 29644409
TI  - Paroxetine ameliorates whole-body allodynia.

PMID- 29644408
TI  - MODUL-a multicenter randomized clinical trial of biomarker-driven maintenance
      therapy following first-line standard induction treatment of metastatic
      colorectal cancer: an adaptable signal-seeking approach.
AB  - PURPOSE: The old approach of one therapeutic for all patients with mCRC is
      evolving with a need to target specific molecular aberrations or cell-signalling
      pathways. Molecular screening approaches and new biomarkers are required to fully
      characterize tumours, identify patients most likely to benefit, and predict
      treatment response. METHODS: MODUL is a signal-seeking trial with a design that
      is highly adaptable, permitting modification of different treatment cohorts and
      inclusion of further additional cohorts based on novel evidence on new
      compounds/combinations that emerge during the study. RESULTS: MODUL is ongoing
      and its adaptable nature permits timely and efficient recruitment of patients
      into the most appropriate cohort. Recruitment will take place over approximately
      5 years in Europe, Asia, Africa, and South America. The design of MODUL with
      ongoing parallel/sequential treatment cohorts means that the overall size and
      duration of the trial can be modified/prolonged based on accumulation of new
      data. CONCLUSIONS: The early success of the current trial suggests that the
      design may provide definitive leads in a patient-friendly and relatively
      economical trial structure. Along with other biomarker-driven trials that are
      currently underway, it is hoped that MODUL will contribute to the continuing
      evolution of clinical trial design and permit a more 'tailored' approach to the
      treatment of patients with mCRC.

PMID- 29644410
TI  - Author Correction to: The transgluteal approach to shockwave lithotripsy to treat
      distal ureter stones: a prospective, randomized, and multicenter study.
AB  - The funding number was incorrect in the original published article. The correct
      funding number should read as follows.

PMID- 29644411
TI  - NOAC monotherapy in patients with concomitant indications for oral
      anticoagulation undergoing transcatheter aortic valve implantation.
AB  - AIMS: Antithrombotic therapy after transcatheter aortic valve implantation (TAVI)
      is highly controversial and guideline recommendations are not evidence based. We
      assessed efficacy and safety of non-vitamin K antagonist oral anticoagulant
      (NOAC) monotherapy in patients with concomitant indications for OAC undergoing
      TAVI. METHODS: Among more than 1300 TAVI patients since 2008, 154 patients were
      identified who received postinterventional NOAC monotherapy. Outcomes were
      compared to 172 patients treated with vitamin K antagonist (VKA) monotherapy.
      Thromboembolic as well as bleeding complications were analysed for 6 months after
      TAVI. RESULTS: Despite high CHA2DS2-Vasc (4.6 +/- 1.2), HEMORR2HAGES (4.7 +/-
      1.9) and HASBLED (2.7 +/- 0.8) scores only three major/life-threatening bleedings
      and four thromboembolic events occurred after NOAC therapy had been initiated
      post-TAVI. 12 patients (7.8%) died within 6 months after the procedure. Compared
      to patients being treated with VKA monotherapy, analysis of a combined end-point
      of post-procedural death, stroke, embolism and severe bleeding revealed no
      significant differences (17/154 vs. 14/172; p = 0.45). CONCLUSIONS: The results
      of this study suggest that NOAC therapy without additional antiplatelet treatment
      is effective and safe in patients with concomitant indications for OAC undergoing
      TAVI.

PMID- 29644413
TI  - Flow-mediated dilation, nitroglycerin-mediated dilation and their ratio predict
      successful renal denervation in mild resistant hypertension.

PMID- 29644415
TI  - Does Simultaneous Liposuction Adversely Affect the Outcome of Thread Lifts? A
      Preliminary Result.
AB  - BACKGROUND: Along with advances in thread lift techniques and materials,
      ancillary procedures such as fat grafting, liposuction, or filler injections have
      been performed simultaneously. Some surgeons think that these ancillary
      procedures might affect the aesthetic outcomes of thread lifting possibly due to
      inadvertent injury to threads or loosening of soft tissue via passing the cannula
      in the surgical plane of the thread lifts. The purpose of the current study is to
      determine the effect of such ancillary procedures on the outcome of thread lifts
      in the human and cadaveric setting. METHODS: We used human abdominal tissue after
      abdominoplasty and cadaveric faces. In the abdominal tissue, liposuction parallel
      to the parallel axis was performed in one area for 5 min. We counted 30 passes
      when liposuction was performed in one direction. This was repeated as we changed
      the direction of passages. The plane of thread lifts (dermal vs subcutaneous) and
      angle between liposuction and thread lifts (parallel vs perpendicular) were
      differentiated in this abdominal tissue study group. Then, we performed parallel
      or perpendicular thread lifts using a small slit incision. Using a tensiometer,
      the maximum holding strength was measured when pulling the thread out of the skin
      as much as possible. We also used faces of cadavers to prove whether the finding
      in human abdominal tissue is really valid with corresponding techniques. RESULTS:
      Our pilot study using abdominal tissue showed that liposuction after thread lifts
      adversely affects it regardless of the vector of thread lifts. In the cadaveric
      study, however, liposuction prior to thread lifting does not significantly affect
      the holding strength of thread lifts. CONCLUSIONS: Liposuction or fat grafting in
      the appropriate layer would not be a hurdle to safely performing simultaneous
      thread lifts if the target lift tissue is intra-SMAS or just above the SMAS
      layer. 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- 29644414
TI  - Bone and Soft Tissue Nasal Angles Discrepancies and Overlying Skin Thickness: A
      Computed Tomography Study.
AB  - BACKGROUND: The aim of this study was to derive the normal values for bone and
      soft tissue nasal angles as well as the overlying skin thickness and to attempt
      to determine the correlation between differences in bone and soft tissue angles
      and overlying skin thickness in Middle Eastern patients. MATERIALS AND METHODS:
      Three-dimensional cephalometric analysis was performed for 100 patients who
      underwent computed tomography of the paranasal sinuses. The nasofrontal angle,
      pyramidal angle-nasal root, pyramidal angle-tip of the nasal bone, and overlying
      skin thickness were measured, and the results were analyzed according to sex,
      age, and body mass index (BMI). RESULTS: All soft tissue angles were
      significantly larger than the bone angles, with the mean difference being 11.62
      degrees , 30.80 degrees , and 27.05 degrees  for the nasofrontal angle (P =
      0.000), pyramidal angle-nasal root (P = 0.000), and pyramidal angle-tip of the
      nasal bone (P = 0.000), respectively. The mean overlying skin thickness was 3.89
      +/- 1.48 mm at the nasion, 1.16 +/- 0.6 mm at the rhinion, and 2.93 +/- .97 mm at
      the nasal tip. Differences in the nasofrontal angle were strongly correlated with
      the skin thickness at the nasion (P = 0.001). CONCLUSION: A simple clinical exam
      of the soft tissue nasal angles does not reflect the underlying bone angles that
      will be encountered during rhinoplasty. BMI does not influence nasal shape, and
      rhinoplasty surgery should take into account the ethnic group, age, and sex of
      the patient. Surgeons should leave a minor skeletal hump at the end of the nasal
      bone for Middle Eastern patients. 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- 29644412
TI  - Patent foramen ovale closure versus medical therapy for prevention of recurrent
      cryptogenic embolism: updated meta-analysis of randomized clinical trials.
AB  - BACKGROUND: We performed an updated meta-analysis of all randomized-controlled
      trials (RCTs) comparing patent foramen ovale (PFO) closure with medical therapy
      for prevention of recurrent ischemic stroke. METHODS AND RESULTS: We searched
      Medline, EMBASE, and Cochrane databases, and proceedings of international
      meetings for RCTs of patients with cryptogenic stroke and PFO comparing
      percutaneous PFO closure versus medical therapy for prevention of recurrent
      ischemic stroke. The primary outcome was a composite ischemic/embolic endpoint
      comprising stroke, transient ischemic attack (TIA), peripheral embolism, and
      early death in the intention-to-treat population. Secondary outcomes were all
      cause death, stroke, TIA, atrial fibrillation (AF), and major bleeding. Of 3440
      enrolled patients across five RCTs, 1829 were allocated to PFO closure and 1611
      to medical therapy. The follow-up ranged from 2 to 5.9 years. PFO closure reduced
      the risk of the composite outcome [HR 0.52, (0.36-0.77); p < 0.01], and stroke,
      [HR 0.39, (0.19-0.83); p < 0.01], and increased the risk of AF [OR 3.75, (2.44
      5.78); p < 0.01] as compared to medical therapy. NNT for stroke was 37 and NNH
      for AF 49, indicating a net clinical benefit of PFO closure. The meta-analysis
      had 95% power to detect a 50% relative risk reduction (RRR) in the primary
      outcome and 89% power to detect a 70% RRR in ischemic stroke. The risk of all
      cause death (HR 1.08, p = 0.90), TIA [HR 0.73, (0.49-1.09); p = 0.12], and major
      bleeding [OR 0.97, (0.44-2.17); p = 0.95] was comparable between the groups.
      CONCLUSIONS: Among patients with cryptogenic stroke and PFO, percutaneous closure
      of PFO is superior to medical therapy in preventing recurrent ischemic/embolic
      events and stroke but is associated with an increased risk of AF.

PMID- 29644416
TI  - Shape, Position and Dimension of the Nipple Areola Complex in the Ideal Male
      Chest: A Quick and Simple Operating Room Technique.
AB  - INTRODUCTION: The anatomical features of the chest identify an individual as male
      or female and even the smallest details of these features determine the
      appropriate appearance for each gender. In female-to-male patients, the creation
      of an aesthetically pleasing male chest is the most important step. Incorrect
      positioning of the nipple areola complex (NAC) on the chest wall and suboptimal
      shaping and sizing of the NAC are common pitfalls in male NAC creation. PATIENTS
      AND METHODS: We have analyzed the anatomical chest features of 26 water polo
      players, to verify our hypothesis of the relationship between the pectoralis
      major muscle and NAC and to create a method for repositioning the NAC that is
      applicable in the operating room, is easy, practical and reproducible without the
      use of formulas and based on an easily identifiable landmark. RESULTS: In our
      reference group, the NAC has a constant relationship with the pectoralis major
      muscle, positioned on average 3 cm medial to the lateral border of the pectoralis
      muscle and 2.5 cm above the inferior pectoralis major insertion. This supports
      our hypothesis and our surgical technique. We use the index finger to find a
      vertical axis and a line 2.5 cm above the inferior pectoralis shadow to find the
      horizontal axis. We also introduce a modification to the receiving site to
      recreate an oval areola more similar to that of an ideal male chest. CONCLUSIONS:
      Our anatomical study and statistical analysis support a consistent relationship
      between the position and shape of the NAC and the borders of the pectoral muscle.
      We have used this relationship to develop our "trick," which is easily applicable
      in the operating room to find the NAC position without using formulas and
      numbers. This method allowed us to place the NAC in a position very close to that
      of a typical male subject, and it permitted us to reduce the surgery time. 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- 29644417
TI  - Longitudinal Analysis of Superficial Midfacial Fat Volumes Over a 10-Year Period.
AB  - BACKGROUND: Volumetric changes to facial fat that occur with aging remain poorly
      understood. The aim of this study was to evaluate for longitudinal changes to
      midfacial fat volumes in a group of individuals. METHODS: We conducted a
      retrospective longitudinal study of adult subjects who underwent multiple facial
      computed tomographic (CT) scans timed at least 8 years apart. Subjects who
      underwent facial surgery or suffered facial trauma were excluded. Facial CT scans
      were analyzed, and superficial cheek fat volumes were measured and compared to
      track changes that occurred with aging. RESULTS: Fourteen subjects were included
      in our analysis of facial aging (5 male, 9 female; mean initial age 50.9 years;
      mean final age 60.4 years). In the right superficial cheek there was an increase
      in mean (SD) superficial fat volume from 10.33 (2.01) to 10.50 (1.80) cc, which
      was not statistically significant (P = 0.75). Similar results were observed in
      the left cheek. There were no statistically significant longitudinal changes to
      caudal, middle, or cephalad subdivisions of bilateral superficial cheek fat. A
      simple linear regression was performed to predict superficial cheek fat pad
      volume based on age which did not reach statistical significance (P = 0.31), with
      an R2 of 0.039. CONCLUSIONS: This study is the first to quantitatively assess for
      longitudinal changes to midfacial fat in a group of individuals. Superficial
      cheek fat remained stable as subjects aged from approximately 50 to 60 years old,
      with no change in total volume or redistribution within a radiographically
      defined compartment. 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- 29644418
TI  - Glandular Liposculpture in the Treatment of Gynecomastia.

PMID- 29644419
TI  - Lower Lateral Cartilage Cephalic Malposition: An Over-Diagnosed Entity.
AB  - BACKGROUND: Lower lateral cartilage malposition is represented by anterior
      convexity of the lower lateral cartilage (LLC) dome with posterior pinch, as
      defined by Sheen and Constantian. This anatomic variation consists of cephalic,
      or upward and inward, rotation of lateral crura, particularly in bulbous tip
      patients. In most cases, "bulbous pinch" LLC is positioned toward the medial
      canthus, not laterally, so it is referred to as cephalic displacement.
      Accordingly, it is recommended to caudally displace cartilage in the majority of
      rhinoplasty cases in which variation is seen. OBJECTIVES: The purpose of this
      paper is to measure the exact angle of lateral crura with fixed reference points
      on the face. METHODS: We drew and marked LLC contours and vertical/horizontal
      lines in 40 consecutive rhinoplasty cases. We then divided them into two groups:
      (1) bulbous pinch and (2) flat LLCs. The right- and left-sided LLC angles to
      midline and horizontal lines were measured and compared to assess whether there
      was any significant difference between the two subgroups. RESULTS: There was no
      significant difference between the angles of LLC rotation in the bulbous and flat
      LLCs groups, measured both vertically and horizontally. CONCLUSION: Based on our
      findings, although cephalic malposition of LLCs may be present in some patients
      but in the majority of cases the etiology of nasal lateral wall pinching is not
      cephalic displacement of lateral crura but most probably is due, rather, to
      severe convexity of the posterior and lateral crura. According to our findings,
      cephalic malposition is an uncommon anatomic variation of LLCs that has been
      reported at high frequency (60-70% of their rhinoplasty cases). This finding may
      help to correct this deformity into a normal anatomic configuration. 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- 29644420
TI  - Soluble TREM-1 as a predictive factor of neonatal sepsis: a meta-analysis.
AB  - BACKGROUND: The efficacy of soluble triggering receptor expressed on myeloid cell
      1 (TREM-1) in detecting sepsis in adults has already been proven. To date,
      however, consensus in the field of neonatal sepsis is lacking. The purpose of the
      present systematic review is to accumulate current evidence in this field. SEARCH
      STRATEGY: We systematically searched Medline (1966-2017), Scopus (2004-2017),
      Clinicaltrials.gov (2008-2017), EMBASE (1980-2017), Cochrane Central Register of
      Controlled Trials CENTRAL (1999-2017) and Google Scholar (2004-2017) along with
      reference lists from included studies. MAIN RESULTS: Eight studies were finally
      included in the present analysis, with a total number of 667 neonates. The
      estimated sensitivity for the summary point was 0.95 [95% CI (0.81-0.99)] and the
      specificity was 0.87 [95% CI (0.56-0.97)]. The diagnostic odds ratio was
      calculated at 132.49 [95% CI (6.85-2560.70)]. Fagan's nomogram demonstrated that
      the post-test probability increased to 71% and decreased to 2%, when the pre-test
      probability was set at 25%. However, significant discrepancy was observed in
      terms of the used cut-offs; therefore, the sensitivity and specificity presented
      in our meta-analysis should be reviewed with caution, as they may present an
      overestimation of the actual predictive efficacy of this protein. CONCLUSION:
      Current evidence suggests that sTREM-1 may become a useful biomarker for the
      prediction of neonatal sepsis. However, the small number of studies and the
      variation of the threshold values limit its implementation in clinical practice.
      Future large-scale studies are needed to determine the optimal cut-off value that
      may discriminate normal levels from those suggestive of the presence of neonatal
      sepsis.

PMID- 29644421
TI  - [Infections after bite wounds : For example rat bite fever due to Streptobacillus
      moniliformis].
AB  - Rat bite fever due to Streptobacillus moniliformis induces typical but not
      pathognomonic clinical signs, such as local purulent wound infection followed by
      maculopapular exanthema, myalgia as well as purulent joint infections. Severe
      complications, such as osteomyelitis and endocarditis are possible. it seems that
      this infection is rarely diagnosed but this infection could be much more common
      because the final diagnostic proof is difficult to achieve. Firstly, the culture
      of these bacteria is critical because the bacteria are fastidious and secondly
      the exact differentiation of the isolates is hardly possible by standard
      laboratory methods. Modern techniques such as mass spectroscopy (MALDI-TOF) and
      molecular biology allow a precise clarification. Surgical cleansing of infection
      sites in combination with a rational antibiotic therapy, for example with beta
      lactam antibiotics, are generally able to cure the infection if treatment is
      started early enough. In addition, vaccinations, for example against tetanus and
      rabies have to be considered in this situation as for all other bite wound
      infections.

PMID- 29644422
TI  - [Etiology, diagnostics and classification of lunate bone necrosis].
AB  - Kienbock's disease, also known as avascular necrosis of the lunate bone describes
      the slowly progressive osteonecrosis of the lunate bone with secondary
      development of osteoarthritis and carpal collapse. In order to emphasize the
      atraumatic origin of the disease, this is normally referred to as aseptic,
      idiopathic or avascular lunate necrosis. There are thought to be a number of
      factors predisposing to Kienbock's disease, such as ulnar negative variance, the
      shape of the lunate itself and various types of vascular anatomy. The ongoing
      development of radiographic techniques in recent years has contributed to a
      better understanding of the progression of the disease and led to a modification
      of the standard classifications. New sophisticated classification methods provide
      the basis for a differentiated treatment. This article provides an overview of
      the current state of knowledge about the etiology and pathogenesis as well as the
      clinically relevant diagnostic procedures and classifications.

PMID- 29644425
TI  - Turbidity Responses from Timber Harvesting, Wildfire, and Post-Fire Logging in
      the Battle Creek Watershed, Northern California.
AB  - The Battle Creek watershed in northern California was historically important for
      its Chinook salmon populations, now at remnant levels due to land and water uses.
      Privately owned portions of the watershed are managed primarily for timber
      production, which has intensified since 1998, when clearcutting became
      widespread. Turbidity has been monitored by citizen volunteers at 13 locations in
      the watershed. Approximately 2000 grab samples were collected in the 5-year
      analysis period as harvesting progressed, a severe wildfire burned 11,200 ha, and
      most of the burned area was salvage logged. The data reveal strong associations
      of turbidity with the proportion of area harvested in watersheds draining to the
      measurement sites. Turbidity increased significantly over the measurement period
      in 10 watersheds and decreased at one. Some of these increases may be due to the
      influence of wildfire, logging roads and haul roads. However, turbidity continued
      trending upwards in six burned watersheds that were logged after the fire, while
      decreasing or remaining the same in two that escaped the fire and post-fire
      logging. Unusually high turbidity measurements (more than seven times the average
      value for a given flow condition) were very rare (0.0% of measurements) before
      the fire but began to appear in the first year after the fire (5.0% of
      measurements) and were most frequent (11.6% of measurements) in the first 9
      months after salvage logging. Results suggest that harvesting contributes to road
      erosion and that current management practices do not fully protect water quality.

PMID- 29644423
TI  - Detection of Echinococcus multilocularis in domestic dogs of Shiqu County in the
      summer herding.
AB  - Alveolar echinococcosis (AE) is one of the most serious parasitic zoonosis in
      Asia. Shiqu County is the most important endemic area of AE in China. Our primary
      objective is to find out the risk factors for Echinococcus multilocularis
      infection in domestic dogs in Shiqu County during the summer herding period. A
      total of 120 fecal samples were collected from 60 ranchers in October 2016.
      Nested PCR (nPCR) was performed to amplify regions of the mitochondrial12S rRNA
      gene of E. multilocularis. The results showed that the infection rates of AE in
      dogs from Qiwu, Yiniu, Changshaganma, Derongma, Mengyi, and Xiazha villages were
      5, 5, 10, 20, 10, and 5%, respectively. It should be stressed that the infected
      dogs will shed eggs through feces and may have a habit of preying on rodents, the
      intermediate host of the parasite, and become re-infected. This investigation
      confirmed the presence of E. multilocularis infection in dogs in Shiqu and
      revealed the risk factors associated with the infection during summer herding.

PMID- 29644426
TI  - [CA19-9 in intrahepatic cholangiocarcinoma : A diagnostic and prognostic
      armamentarium?]
AB  - BACKGROUND: Intrahepatic cholangiocarcinomas are the second most common malignant
      tumors of the liver with an unfavorable prognosis. The role of CA19-9 in terms of
      patient prognosis is still under debate in the literature. OBJECTIVE: The aim of
      the present study was to investigate the prognostic value of preoperatively
      assessed CA19-9 levels in patients with intrahepatic cholangiocarcinoma after
      surgery. MATERIAL AND METHODS: A total of 63 patients suffering from intrahepatic
      cholangiocarcinoma underwent surgery between March 2001 and February 2013 at the
      West German Cancer Center in Essen, Germany. The follow-up ended in December
      2017. The UICC stages, clinicopathological parameters and postoperative tumor
      specific survival rates were analyzed with respect to preoperatively measured
      CA19-9 serum levels. RESULTS: Increased CA19-9 serum levels correlated with
      higher UICC tumor stages and other unfavorable clinicopathological parameters.
      Moreover, patients with preoperative elevated CA19-9 serum levels displayed
      significantly reduced overall survival rates (especially >1000 U/ml vs. <=1000
      U/ml; median overall survival: 14.05 months vs. 42.40 months; p = 0.0003).
      CONCLUSION: Preoperatively assessed CA19-9 levels >1000 U/ml are a strong
      negative prognostic factor of postoperative disease-specific survival in patients
      suffering from intrahepatic cholangiocarcinoma. Future studies are necessary to
      evaluate if patients with highly elevated CA19-9 serum levels should be
      considered for modified treatment strategies (e. g. neoadjuvant or adjuvant
      therapy).

PMID- 29644427
TI  - [Gender-specific differences of the early postoperative and oncosurgical long
      term outcome in rectal cancer-data obtained in a prospective multicenter
      observational study].
AB  - BACKGROUND: Gender-specific aspects have been increasingly considered in clinical
      medicine, also in oncological surgery. AIM: To analyze gender-specific
      differences of early postoperative and oncological outcomes after rectal cancer
      resection based on data obtained in a prospective multicenter observational
      study. PATIENTS AND METHODS: As part of the multicenter prospective observational
      study "Quality assurance in primary rectal cancer", data on tumor site, exogenic
      and endogenic risk factors, neoadjuvant treatment, surgical procedures, tumor
      stage, intraoperative and postoperative complications of patients with the
      histological diagnosis of rectal cancer were registered. Data from the years 2005
      2006 and 2010-2011 were investigated with respect to gender-specific differences
      of postoperative morbidity, hospital mortality, local recurrency rate, disease
      free and overall survival by univariable and multivariable analyses. RESULTS:
      Overall, data from 10,657 patients were evaluated: 60.9% of the patients were
      male, who were significantly younger (p < 0.001). Men had a significantly higher
      rate of alcohol (p < 0.001) and nicotine abuse (p < 0.001) as well as a trend to
      a higher body mass index (BMI) compared with women. Although, there was no
      significant difference in the distribution of various tumor stages comparing men
      and women, neoadjuvant radiochemotherapy was used significantly more often in
      male patients (p < 0.001). In addition, male patients underwent an
      abdominoperineal rectum exstirpation more often, whereas creation of an
      enterostoma and Hartmann's procedure were more frequently used in women (p <
      0.001 each). Multivariate analysis revealed that male patients developed a higher
      overall morbidity (odds ratio, OR: 1.5; p < 0.001) during both study periods and
      from 2010-2011 a higher hospital mortality (OR: 1.8; p < 0.001). After a median
      follow-up period of 36 months, gender did not have a significant impact on
      overall survival, disease-free survival or on the local tumor recurrency. The 5
      year overall survival was 60.5%, disease-free survival 63.8% and local recurrency
      rate was 5%. CONCLUSION: Independent of other variables, gender differences were
      found with respect to early postoperative outcome but not to oncological long
      term results after surgery of rectal cancer.

PMID- 29644428
TI  - Assessment of the scalability of a microtiter plate system for screening of
      oleaginous microorganisms.
AB  - Recent developments in molecular biology and metabolic engineering have resulted
      in a large increase in the number of strains that need to be tested, positioning
      high-throughput screening of microorganisms as an important step in bioprocess
      development. Scalability is crucial for performing reliable screening of
      microorganisms. Most of the scalability studies from microplate screening systems
      to controlled stirred-tank bioreactors have been performed so far with
      unicellular microorganisms. We have compared cultivation of industrially relevant
      oleaginous filamentous fungi and microalga in a Duetz-microtiter plate system to
      benchtop and pre-pilot bioreactors. Maximal glucose consumption rate, biomass
      concentration, lipid content of the biomass, biomass, and lipid yield values
      showed good scalability for Mucor circinelloides (less than 20% differences) and
      Mortierella alpina (less than 30% differences) filamentous fungi. Maximal glucose
      consumption and biomass production rates were identical for Crypthecodinium
      cohnii in microtiter plate and benchtop bioreactor. Most likely due to shear
      stress sensitivity of this microalga in stirred bioreactor, biomass concentration
      and lipid content of biomass were significantly higher in the microtiter plate
      system than in the benchtop bioreactor. Still, fermentation results obtained in
      the Duetz-microtiter plate system for Crypthecodinium cohnii are encouraging
      compared to what has been reported in literature. Good reproducibility
      (coefficient of variation less than 15% for biomass growth, glucose consumption,
      lipid content, and pH) were achieved in the Duetz-microtiter plate system for
      Mucor circinelloides and Crypthecodinium cohnii. Mortierella alpina cultivation
      reproducibility might be improved with inoculation optimization. In conclusion,
      we have presented suitability of the Duetz-microtiter plate system for the
      reproducible, scalable, and cost-efficient high-throughput screening of
      oleaginous microorganisms.

PMID- 29644429
TI  - High diversity of potential nitrate-reducing Fe(II)-oxidizing bacteria enriched
      from activated sludge.
AB  - Nitrate-dependent Fe(II) oxidation (NDFO) has been discovered in various
      environments including activated sludge and can potentially be used to remove
      nitrate from wastewater. In this study, NDFO sludge was successfully enriched
      from activated sludge under high Fe(II) concentrations over 100 days and the
      denitrification rate achieved 1.37 mmol N/(gVSS day). High-throughput sequencing
      of the bacterial 16S rRNA gene was used to investigate the microbial community
      structure dynamics during the enrichment process. The results showed that the
      microbial community changed significantly and high diversity of potential Fe(II)
      oxidizing bacteria (FeOB) was observed in the enriched sludge. Thermomonas and
      Gallionella were the dominant bacterial genera in the enriched sludge and their
      relative abundances accounted for 9.49 and 4.08%, respectively. Furthermore, it
      was found that potential FeOB were also abundantly present in activated sludge
      samples of common municipal wastewater treatment plants. Collectively, this study
      demonstrated that NDFO could be successfully performed by enriched activated
      sludge and high diversity of bacteria is involved in this process, and the
      results also provide baseline information for future research and engineering
      application of NDFO process.

PMID- 29644431
TI  - Machine learning modeling of plant phenology based on coupling satellite and
      gridded meteorological dataset.
AB  - Changes in the timing of plant phenological phases are important proxies in
      contemporary climate research. However, most of the commonly used traditional
      phenological observations do not give any coherent spatial information. While
      consistent spatial data can be obtained from airborne sensors and preprocessed
      gridded meteorological data, not many studies robustly benefit from these data
      sources. Therefore, the main aim of this study is to create and evaluate
      different statistical models for reconstructing, predicting, and improving
      quality of phenological phases monitoring with the use of satellite and
      meteorological products. A quality-controlled dataset of the 13 BBCH plant
      phenophases in Poland was collected for the period 2007-2014. For each
      phenophase, statistical models were built using the most commonly applied
      regression-based machine learning techniques, such as multiple linear regression,
      lasso, principal component regression, generalized boosted models, and random
      forest. The quality of the models was estimated using a k-fold cross-validation.
      The obtained results showed varying potential for coupling meteorological derived
      indices with remote sensing products in terms of phenological modeling; however,
      application of both data sources improves models' accuracy from 0.6 to 4.6 day in
      terms of obtained RMSE. It is shown that a robust prediction of early
      phenological phases is mostly related to meteorological indices, whereas for
      autumn phenophases, there is a stronger information signal provided by satellite
      derived vegetation metrics. Choosing a specific set of predictors and applying a
      robust preprocessing procedures is more important for final results than the
      selection of a particular statistical model. The average RMSE for the best models
      of all phenophases is 6.3, while the individual RMSE vary seasonally from 3.5 to
      10 days. Models give reliable proxy for ground observations with RMSE below 5
      days for early spring and late spring phenophases. For other phenophases, RMSE
      are higher and rise up to 9-10 days in the case of the earliest spring
      phenophases.

PMID- 29644430
TI  - Pathology of idiopathic non-cirrhotic portal hypertension.
AB  - Idiopathic non-cirrhotic portal hypertension is an under-recognized vascular
      liver disease of unknown etiology, characterized by clinical signs of portal
      hypertension in the absence of cirrhosis. By definition, any disorder known to
      cause portal hypertension in the absence of cirrhosis and any cause of chronic
      liver disease must be excluded to make a diagnosis of idiopathic non-cirrhotic
      portal hypertension. However, the diagnosis is often difficult because the
      disease resembles cirrhosis and there is no gold standard test. Liver biopsy is
      an essential tool: it is able to exclude cirrhosis and other causes of portal
      hypertension and it allows the identification of the characteristic lesions.
      Nonetheless, the histological diagnosis of idiopathic non-cirrhotic portal
      hypertension is not always straightforward, in particular by needle biopsy
      samples, because there is no pathognomonic lesion, but rather a variety of
      vascular changes which are unevenly distributed, very subtle, and not all
      necessarily identified in a single specimen. Pathologists should be able to
      recognize several patterns of injury, involving portal/periportal areas as well
      as parenchymal structures.The histological features of idiopathic non-cirrhotic
      portal hypertension are described in this review, focusing on their
      interpretation in needle biopsy specimens.

PMID- 29644432
TI  - Development and application of artificial neural network models to estimate
      values of a complex human thermal comfort index associated with urban heat and
      cool island patterns using air temperature data from a standard meteorological
      station.
AB  - The present study deals with the development and application of artificial neural
      network models (ANNs) to estimate the values of a complex human thermal comfort
      discomfort index associated with urban heat and cool island conditions inside
      various urban clusters using as only inputs air temperature data from a standard
      meteorological station. The index used in the study is the Physiologically
      Equivalent Temperature (PET) index which requires as inputs, among others, air
      temperature, relative humidity, wind speed, and radiation (short- and long-wave
      components). For the estimation of PET hourly values, ANN models were developed,
      appropriately trained, and tested. Model results are compared to values
      calculated by the PET index based on field monitoring data for various urban
      clusters (street, square, park, courtyard, and gallery) in the city of Athens
      (Greece) during an extreme hot weather summer period. For the evaluation of the
      predictive ability of the developed ANN models, several statistical evaluation
      indices were applied: the mean bias error, the root mean square error, the index
      of agreement, the coefficient of determination, the true predictive rate, the
      false alarm rate, and the Success Index. According to the results, it seems that
      ANNs present a remarkable ability to estimate hourly PET values within various
      urban clusters using only hourly values of air temperature. This is very
      important in cases where the human thermal comfort-discomfort conditions have to
      be analyzed and the only available parameter is air temperature.

PMID- 29644433
TI  - Boron application improves yield of rice cultivars under high temperature stress
      during vegetative and reproductive stages.
AB  - It is reported that high temperatures (HT) would cause a marked decrease in world
      rice production. In tropical regions, high temperatures are a constraint to rice
      production and the most damaging effect is on spikelet sterility. Boron (B) plays
      a very important role in the cell wall formation, sugar translocation, and
      reproduction of the rice crop and could play an important role in alleviating
      high temperature stress. A pot culture experiment was conducted to study the
      effect of B application on high temperature tolerance of rice cultivars in B
      deficient soil. The treatments comprised of four boron application treatments
      viz. control (B0), soil application of 1 kg B ha-1 (B1), soil application of 2 kg
      B ha-1 (B2), and foliar spray of 0.2% B (Bfs); three rice cultivars viz.
      Annapurna (HT stress tolerant), Naveen, and Shatabdi (both HT stress
      susceptible); and three temperature regimes viz. ambient (AT), HT at vegetative
      stage (HTV), and HT at reproductive stage (HTR). The results revealed that high
      temperature stress during vegetative or flowering stage reduced grain yield of
      rice cultivars mainly because of low pollen viability and spikelet fertility. The
      effects of high temperature on the spikelet fertility and grain filling varied
      among cultivars and the growth stages of plant when exposed to the high
      temperature stress. Under high temperature stress, the tolerant cultivar displays
      higher cell membrane stability, less accumulation of osmolytes, more antioxidant
      enzyme activities, and higher pollen viability and spikelet fertility than the
      susceptible cultivars. In the present work, soil application of boron was
      effective in reducing the negative effects of high temperature both at vegetative
      and reproductive stages. Application of B results into higher grain yield under
      both ambient and high temperature condition over control for all the three
      cultivars; however, more increase was observed for the susceptible cultivar over
      the tolerant one. The results suggest that the exogenous application of boron had
      a substantial effect on cell membrane stability, sugar mobilization, pollen
      viability, and spikelet fertility, hence the yield. The cultivars due to their
      variation in the tolerance level for high temperature stress behaved differently,
      and at high temperature stress, more response of the application of boron was
      seen in susceptible cultivars.

PMID- 29644434
TI  - Successful treatment of antisynthetase syndrome presenting as rhabdomyolysis with
      rituximab.
AB  - Rhabdomyolysis is a syndrome of muscle necrosis with subsequent release of
      intracellular content into the blood. There are various causes for rhabdomyolysis
      that include trauma, medications and rarely autoimmune conditions such as
      autoimmune myositis. Antisynthetase syndrome is an autoimmune condition
      characterized by positive antisynthetase antibody, myopathy, lung disease and
      arthritis. To our knowledge, rhabdomyolysis in antisynthetase syndrome has not
      been reported in the literature. In this report, we present a patient who
      presented with features of rhabdomyolysis and was diagnosed with antisynthetase
      syndrome. This patient was treated with systemic steroids with partial
      improvement, followed by rituximab, which led to significant improvement in his
      condition. In addition, we summarize all cases reported in the literature of
      inflammatory myopathy-associated rhabdomyolysis.

PMID- 29644435
TI  - Sexual health in patients with rheumatoid arthritis and the association between
      physical fitness and sexual function: a cross-sectional study.
AB  - The aim of this study was to examine sexual health in patients with rheumatoid
      arthritis (RA), and to analyse factors associated with sexual health with a focus
      on physical fitness. One hundred RA patients aged between 18 and 65 years were
      included in a cross-sectional study. Handgrip strength and knee extensor strength
      were measured with a dynamometer, and physical performance with the Short
      Physical Performance Battery (SPPB). Fifty-four patients, mean age 47.8 (SD 10.6)
      years, 61% female, answered a questionnaire about sexual health. Fifty-seven
      percent reported, at least, sometimes having difficulty with sexual intercourse
      (27.8% due to joint stiffness, 24.1% due to fatigue, 18.5% due to pain). Handgrip
      strength and knee extensor strength significantly correlated with the desire to
      engage in sexual intercourse, frequency of sexual contact and satisfaction with
      overall sex life. The SPPB total score correlated with satisfaction with overall
      sex life, and the SPPB repeated chair stands test with the desire to have sexual
      intercourse and satisfaction with overall sex life. After adjusting for age,
      gender, disease activity, comorbidity, co-medication and pain intensity, the
      repeated chair stands test remained significantly associated with the frequency
      of sexual contact (0.53; 0.01-1.05) and with satisfaction with overall sex life
      (1.39; 0.28-2.51). The results of this study show that problems with sexual
      health are highly prevalent in patients with RA. The ability to rise from a chair
      is associated with sexual function, independent of disease activity and pain
      intensity.

PMID- 29644436
TI  - The neural effects of positively and negatively re-experiencing mental fatigue
      sensation: a magnetoencephalography study.
AB  - Fatigue sensation is an essential biological alarm that urges us to take rest to
      avoid disrupting homeostasis and thus plays an important role in maintaining well
      being. However, there are situations in which the anticipation of unpleasant
      fatigue sensation undesirably reduces motivation for activity. The aim of this
      study was to examine whether thinking positively about the fatigue sensation
      would increase motivation to accomplish the workload. Fourteen healthy male
      volunteers participated in this study and performed a two-back test for 30 min to
      induce mental fatigue sensation. After their subjective level of fatigue had
      recovered to the baseline level, they re-experienced the fatigue sensation
      experienced in the two-back test positively, negatively, and without any
      modification (i.e., re-experienced the fatigue sensation as it was). The level of
      motivation to perform another two-back test they felt during the re-experiencing
      was assessed. The neural activity related to the re-experiencing was recorded
      using magnetoencephalography. The level of the motivation to perform another two
      back test was increased by positively re-experiencing the fatigue sensation. The
      increase in delta band power in Brodmann area 7 was positively associated with
      the increase in motivation. These results show that positive thinking about
      fatigue sensation can enhance motivation and suggest that this enhanced
      motivation may have some effects on visual attention system.

PMID- 29644437
TI  - A paperfluidic platform to detect Neisseria gonorrhoeae in clinical samples.
AB  - Globally, the microbe Neisseria gonorrhoeae (NG) causes 106 million newly
      documented sexually transmitted infections each year. Once appropriately
      diagnosed, NG infections can be readily treated with antibiotics, but high-risk
      patients often do not return to the clinic for treatment if results are not
      provided at the point of care. A rapid, sensitive molecular diagnostic would help
      increase NG treatment and reduce the prevalence of this sexually transmitted
      disease. Here, we report on the design and development of a rapid, highly
      sensitive, paperfluidic device for point-of-care diagnosis of NG. The device
      integrates patient swab sample lysis, nucleic acid extraction, thermophilic
      helicase-dependent amplification (tHDA), an internal amplification control
      (NGIC), and visual lateral flow detection within an 80 min run time. Limits of NG
      detection for the NG/NGIC multiplex tHDA assay were determined within the device,
      and clinical performance was validated retroactively against qPCR-quantified
      patient samples in a proof-of-concept study. This paperfluidic diagnostic has a
      clinically relevant limit of detection of 500 NG cells per device with analytical
      sensitivity down to 10 NG cells per device. In triplicate testing of 40 total
      urethral and vaginal swab samples, the device had 95% overall sensitivity and
      100% specificity, approaching current laboratory-based molecular NG diagnostics.
      This diagnostic platform could increase access to accurate NG diagnoses to those
      most in need.

PMID- 29644438
TI  - Comparative phosphoproteomic analysis reveals differentially phosphorylated
      proteins regulate anther and pollen development in kenaf cytoplasmic male
      sterility line.
AB  - Cytoplasmic male sterility (CMS) is widely used in plant breeding and represents
      a perfect model to understand cyto-nuclear interactions and pollen development
      research. Protein phosphorylation is ubiquitous and is involved in the regulation
      of diverse cellular processes. To reveal the possible mechanism of CMS and pollen
      development in kenaf, we performed an iTRAQ-based comparative phosphoproteome
      analysis in the anthers of a CMS line and wild-type plant (Wt). Whole
      transcriptome unigenes of kenaf as the reference genome, we identified a total of
      3045 phosphorylated sites on 1640 peptides corresponding to 974 unique proteins.
      292 of the peptides which corresponding to 247 unique proteins were
      differentially phosphorylated (fold change >= 1.20 with P value< 0.05) between
      these two materials. 113 and 134 proteins were characterized as up-regulated or
      down-regulated phosphorylated, respectively. An evaluation of the phosphoproteome
      and proteomic results indicated that the most significantly phosphorylated
      proteins were not associated with abundant changes at the protein level.
      Bioinformatics analysis demonstrated that many of these proteins were involved in
      various biological processes which may play key roles in pollen development,
      including carbohydrate metabolism, energy metabolism, transport, gene expression
      regulation, signal transduction, and cell cycle control. Our results provide
      insight into the CMS mechanism and pollen development in kenaf from a protein
      phosphorylation perspective.

PMID- 29644439
TI  - Comparative effects of antidepressant medications and untreated major depression
      on pregnancy outcomes: a systematic review.
AB  - Psychopharmacological treatment of pregnant women is an area of continued
      controversy; extensive observational research on the use of antidepressant
      medications in pregnancy has found these medications to be associated with
      increased risk of spontaneous abortion, preterm delivery, and low birth weight.
      However, depression itself has also been associated with increased risk of those
      same outcomes, and only recently have researchers begun trying to compare treated
      with untreated depression. The purpose of this study was to conduct a systematic
      review of the literature to integrate those comparative studies and compare risks
      and benefits. PubMed, PsycInfo, and CINAHL searches; study selection; and data
      extraction were carried out using PRISMA guidelines. Eleven prospective
      observational and case-control studies were selected for final inclusion. Risk of
      low birth weight and related outcomes do not differ between antidepressant
      treated pregnant women and untreated depressed women. Average gestational lengths
      tend to be slightly shorter with antidepressant use but it is unclear whether
      these differences are clinically meaningful or extend to preterm delivery. Very
      limited research on spontaneous abortion did not allow conclusions to be drawn
      regarding that outcome. The low number of studies meeting criteria highlights the
      need for further research to aid in risk-benefit analysis for women considering
      antidepressant use in pregnancy. While further research is necessary,
      discontinuing antidepressant treatment of major depression in pregnancy due to
      concerns about length of gestation, birth weight, or spontaneous abortion is not
      supported by the evidence available at this time.

PMID- 29644440
TI  - A liquid biopsy in primary lung cancer.
AB  - A tissue biopsy is the "golden standard" for molecular profiling that is
      essential in decision-making regarding treatment for malignant tumors, including
      primary lung cancer. However, tumor biopsies are associated with several
      limitations, including invasiveness and difficulty in achieving access. Liquid
      biopsies have several potential advantages over tissue biopsies, and recent
      advances in molecular technologies have enabled liquid biopsies to be introduced
      into daily clinical practice. Cell-free blood-based liquid biopsies to detect
      mutations in the epidermal growth factor receptor (EGFR) gene in the plasma have
      been approved and may be useful in selecting patients for treatment with tyrosine
      kinase inhibitors of EGFR. We herein describe blood-based liquid biopsies and
      review the current status and future perspectives of plasma genotyping in primary
      lung cancer.

PMID- 29644441
TI  - [11C]acetate PET as a tool for diagnosis of liver steatosis.
AB  - PURPOSE: To investigate [11C]acetate PET-surrogate parameter of fatty acid
      synthase activity-as suitable tool for diagnosis and monitoring of liver
      steatosis. METHODS: In this retrospective study, data were obtained from 83
      prostatic carcinoma patients from 1/2008 to 1/2014. Mean HU was calculated from
      unenhanced CT of all patients from liver with liver HU less than 40 as threshold
      for liver steatosis. SUVmax of the liver and of the blood pool in thoracic aorta
      (as background for calculation of a liver/background ratio [SUVl/b]) was
      measured. t test was used with a P < 0.05 considered as statistically significant
      difference and ROC analysis was used for calculating specificity and sensitivity.
      RESULTS: 19/83 patients (20%) had diagnosis of hepatic steatosis according to CT.
      Uptake of [11C]acetate was significantly higher in patients with hepatic
      steatosis as compared to control group (SUVmax 7.96 +/- 2.0 vs. 5.48 +/- 2.3 [P <
      0.001]). There was also a significant correlation between both SUVmax (r = -
      0.52, P < 0.001) and SUVl/b (r = - 0.59, P < 0.001) with the density (HU) of the
      liver. In ROC analysis for detection of liver steatosis SUVmax (threshold: 5.86)
      had a sensitivity of 94% and specificity of 69% with an AUC of 0.81. Increasing
      body mass index is correlated with the severity of steatosis. CONCLUSION: We
      showed for the first time that hepatic steatosis associates with increased
      [11C]acetate uptake. Also, severity of steatosis correlates with [11C]acetate
      uptake. [11C]acetate uptake PET seems promising for the assessment of liver
      steatosis.

PMID- 29644442
TI  - [Current aspects of the definition and diagnosis of sepsis and antibiotic
      resistance].
AB  - Hospital mortality of patients with secondary sepsis remains high at around 40%.
      Because of the methodological deficiencies of the definitions used so far, valid
      epidemiological data on secondary sepsis that allow for national and
      international comparisons are lacking. Since 2016, new clinical diagnostic tools
      that are also suitable for sepsis screening outside of intensive care units have
      been available. To counteract the high mortality of nosocomial sepsis, new
      approaches to the early identification of at-risk patients are needed. An
      adequate blood culture sampling rate and a high preanalytical quality should be
      established as a basis for quality assurance, especially in the field of
      nosocomial bloodstream infections; otherwise, there is a risk of surveillance
      bias. Data from laboratory-based antibiotic resistance surveillance on MRSA in
      blood culture isolates have shown a downward trend over the last 4 years. In Gram
      negative pathogens, a relatively stable resistance situation has been observed
      over this period for many of the pathogen-antibiotic combinations.

PMID- 29644443
TI  - In-Situ Molecular Vapor Composition Measurements During Lyophilization.
AB  - PURPOSE: Monitoring process conditions during lyophilization is essential to
      ensuring product quality for lyophilized pharmaceutical products. Residual gas
      analysis has been applied previously in lyophilization applications for leak
      detection, determination of endpoint in primary and secondary drying, monitoring
      sterilization processes, and measuring complex solvents. The purpose of this
      study is to investigate the temporal evolution of the process gas for various
      formulations during lyophilization to better understand the relative extraction
      rates of various molecular compounds over the course of primary drying. METHODS:
      In this study, residual gas analysis is used to monitor molecular composition of
      gases in the product chamber during lyophilization of aqueous formulations
      typical for pharmaceuticals. Residual gas analysis is also used in the
      determination of the primary drying endpoint and compared to the results obtained
      using the comparative pressure measurement technique. RESULTS: The dynamics of
      solvent vapors, those species dissolved therein, and the ballast gas (the gas
      supplied to maintain a set-point pressure in the product chamber) are observed
      throughout the course of lyophilization. In addition to water vapor and nitrogen,
      the two most abundant gases for all considered aqueous formulations are oxygen
      and carbon dioxide. In particular, it is observed that the relative
      concentrations of carbon dioxide and oxygen vary depending on the formulation, an
      observation which stems from the varying solubility of these species. This result
      has implications on product shelf life and stability during the lyophilization
      process. CONCLUSIONS: Chamber process gas composition during lyophilization is
      quantified for several representative formulations using residual gas analysis.
      The advantages of the technique lie in its ability to measure the relative
      concentration of various species during the lyophilization process. This feature
      gives residual gas analysis utility in a host of applications from endpoint
      determination to quality assurance. In contrast to other methods, residual gas
      analysis is able to determine oxygen and water vapor content in the process gas.
      These compounds have been shown to directly influence product shelf life. With
      these results, residual gas analysis technique presents a potential new method
      for real-time lyophilization process control and improved understanding of
      formulation and processing effects for lyophilized pharmaceutical products.

PMID- 29644445
TI  - [Perioperative onset of sarcoidosis : Rare differential diagnosis of a difficult
      airway].
AB  - Sarcoidosis is a rare multisystemic chronic inflammatory condition. Typically,
      there is a big discrepancy between the patient's subjectively perceived symptoms
      and the presence of clinical signs. Due to the high number of potential sites of
      onset (e. g. larynx, lungs, heart, liver, kidneys) the affected organs may show
      functional restrictions that are relevant for decisions related to anesthesia.
      Therefore, an anesthetists working in a clinical setting should be familiar with
      the special needs of this patient collective. This article describes the onset of
      sarcoidosis in a case of an unexpected difficult airway.

PMID- 29644444
TI  - [S3 guidelines on intensive medical care of cardiac surgery patients :
      Hemodynamic monitoring and cardiovascular system-an update].
AB  - An update of the S3- guidelines for treatment of cardiac surgery patients in the
      intensive care unit, hemodynamic monitoring and cardiovascular system was
      published by the Association of Scientific Medical Societies in Germany (AWMF) in
      January 2018. This publication updates the guidelines from 2006 and 2011. The
      guidelines include nine sections that in addition to different methods of
      hemodynamic monitoring also reviews the topic of volume therapy as well as
      vasoactive and inotropic drugs. Furthermore, the guidelines also define the goals
      for cardiovascular treatment. This article describes the most important
      innovations of these comprehensive guidelines.

PMID- 29644446
TI  - Effective Identification of Similar Patients Through Sequential Matching over ICD
      Code Embedding.
AB  - Evidence-based medicine often involves the identification of patients with
      similar conditions, which are often captured in ICD (International Classification
      of Diseases (World Health Organization 2013)) code sequences. With no satisfying
      prior solutions for matching ICD-10 code sequences, this paper presents a method
      which effectively captures the clinical similarity among routine patients who
      have multiple comorbidities and complex care needs. Our method leverages the
      recent progress in representation learning of individual ICD-10 codes, and it
      explicitly uses the sequential order of codes for matching. Empirical evaluation
      on a state-wide cancer data collection shows that our proposed method achieves
      significantly higher matching performance compared with state-of-the-art methods
      ignoring the sequential order. Our method better identifies similar patients in a
      number of clinical outcomes including readmission and mortality outlook. Although
      this paper focuses on ICD-10 diagnosis code sequences, our method can be adapted
      to work with other codified sequence data.

PMID- 29644447
TI  - Genome-wide identification of hexokinase gene family in Brassica napus:
      structure, phylogenetic analysis, expression, and functional characterization.
AB  - MAIN CONCLUSION: Genome-wide identification, expression analysis, and functional
      characterization of previously uncharacterized hexokinase family of oil crop,
      Brassica napus, underscore the importance of this gene family in plant growth and
      development. In plants, the multi-gene family of dual-function hexokinases (HXKs)
      plays important roles in sugar metabolism and sensing that affect growth and
      development. Rapeseed (Brassica napus L.) is an important oil crop; however,
      little is known about the B. napus HXK gene family. We identified 19 putative
      HXKs in B. napus genome. B. rapa and B. oleracea, the two diploid progenitors of
      B. napus, contributed almost equally to the BnHXK genes. Phylogenetic analysis
      divided the 19 BnHXKs into four groups. The exon-intron structures of BnHXKs
      share high similarity to those of HXKs in Arabidopsis and rice. The group III and
      IV BnHXKs are highly expressed in roots, whereas group I members preferentially
      express in leaves. Analysis of seed transcriptomes at different developmental
      stages showed that most of group I and IV HXKs are highly expressed 2-weeks after
      pollination (2WAP), compared to 4WAP for group III. BnHKXs are differentially
      expressed in susceptible and tolerant B. napus cultivars after fungal infection,
      suggesting the possible involvement in defense response. We generated rapeseed
      RNAi lines for BnHXK9, a member of relatively less characterized group IV, by
      pollen-mediated gene transformation. The seedlings of BnHXK9-RNAi lines showed
      delayed growth compared to the wild type. The RNAi plants were dwarf with curly
      leaves, suggesting the involvement of BnHXK9 in plant development. Collectively,
      our findings provides a comprehensive account of BnHXK gene family in an
      important crop and a starting point for further elucidation of their roles in
      sugar metabolism and sensing, as well as plant growth and development.

PMID- 29644448
TI  - Total mercury, methyl mercury, and heavy metal concentrations in Hyeongsan River
      and its tributaries in Pohang city, South Korea.
AB  - Heavy metal contamination in aquatic systems is a big problem in many areas
      around the world. In 2016, high mercury concentrations were reported in bivalves
      (Corbicula leana) and sediments near the confluence of the Hyeongsan River and
      Chilseong Creek located in Pohang, a steel industrial city in the south-east
      coast of the Korean peninsula. Given that both the Chilseong and Gumu creeks run
      through the Pohang industrial complex and ultimately flow to the Hyeongsan River,
      it is imperative to determine if the industrial effluents have any impact on the
      mercury contamination in these two streams and the Hyeongsan River. In this work,
      we investigated the concentration levels of different heavy metals using cold
      vapor atomic fluorescence spectroscopy and inductively coupled plasma-mass
      spectroscopy. The metal concentration in the water samples from the Hyeongsan
      River, Gumu Creek, and Chilseong Creek did not exceed the limits for drinking
      water quality set by the US EPA and World Health Organization. However, the
      sediment samples were found to be heavily contaminated by Hg with levels
      exceeding the toxic effect threshold. Gumu Creek was found to be heavily
      contaminated. The concentrations of the different heavy metals increased
      downstream, and the samples collected from the sites in the Hyeongsan River near
      the Gumu Creek, an open channel for wastewater discharge of companies in the
      Pohang Industrial Complex, showed higher contamination levels, indicating that
      the effluents from the industrial complex are a possible source of contamination
      in the river.

PMID- 29644449
TI  - Predictive performance of dual modality of computed tomography angiography and
      intravascular ultrasound for no-reflow phenomenon after percutaneous coronary
      stenting in stable coronary artery disease.
AB  - Attenuated plaque on intravascular ultrasound (IVUS) and low attenuation plaque
      on computed tomography angiography (CTA) are associated with no-reflow phenomenon
      during percutaneous coronary intervention (PCI). However, evaluation by a single
      modality has been unable to satisfactorily predict this phenomenon. We
      investigated whether the combination of IVUS and CTA findings can ameliorate the
      predictive potential for no-reflow phenomenon after stent implantation during PCI
      in stable coronary artery disease (CAD). A total of 988 lesions of 707 stable CAD
      patients who underwent coronary CTA before PCI were enrolled. PCI was performed
      with preprocedural IVUS and stent implantation. As for plaque characters, very
      low attenuation plaque (CTA v-LAP) whose minimum density was < 0 Hounsfield units
      on CTA and attenuated plaque (IVUS AP) on IVUS were evaluated. No-reflow
      phenomenon was observed in 22 lesions (2.2%) of 19 patients (2.7%). Both CTA v
      LAP and IVUS AP were much more frequently observed in patients with no-reflow
      phenomenon. Positive (PPV) and negative predictive values (NPV) and accuracy for
      prediction of no-reflow were almost equivalent between CTA v-LAP (13.2, 99.6, and
      87.0%) and IVUS AP (15.7, 99.8, and 89.0%). The combination of CTA v-LAP and IVUS
      AP markedly ameliorated PPV (31.7%) without deterioration of NPV (99.7%) and
      increased the diagnostic accuracy (95.5%). These findings showed that the
      combination of CTA v-LAP and IVUS AP improved the predictive power for no-reflow
      phenomenon after coronary stenting in stable CAD patients, suggesting the
      usefulness of combined estimation by using CTA and IVUS for predicting no-reflow
      phenomenon during PCI in clinical practice.

PMID- 29644450
TI  - Monitoring and Management of Toxicities of Novel B Cell Signaling Agents.
AB  - PURPOSE REVIEW: B cell signaling agents, including ibrutinib, idelalisib, and the
      BCL-2 inhibitor venetoclax have become an integral part of therapy for patients
      with non-Hodgkin's lymphomas. The toxicity profiles of these medications is
      distinct from chemoimmunotherapy. Here, we will review the mechanism of action of
      these drugs, their efficacy, and toxicity management. RECENT FINDINGS: Ibrutinib
      use is associated with increased risk of atrial fibrillation and bleeding which
      can be managed using dose interruptions and modifications. Patients on idelalisib
      require close clinical and frequent laboratory monitoring, particularly of liver
      function tests to ensure there are no serious adverse events. Monitoring for
      infections is important in patients on both idelalisib and ibrutinib. Venetoclax
      requires close clinical and laboratory monitoring to prevent significant tumor
      lysis. Targeted B cell receptor therapies each have unique side effect profiles
      which require careful clinical monitoring. As we continue to use these therapies,
      optimal management strategies will continue to be elucidated.

PMID- 29644451
TI  - Emerging Therapies in Metastatic Prostate Cancer.
AB  - PURPOSE OF REVIEW: In the last decade, there have been multiple landmark
      therapeutic advances for the treatment of metastatic prostate cancer, both in the
      castration-resistant and hormone-sensitive setting. In this review, we highlight
      recent progress and ongoing trials for metastatic prostate cancer, including
      advances in chemotherapy, androgen receptor-directed therapy, targeted therapies,
      and immunotherapy. RECENT FINDINGS: Several landmark studies for men with
      metastatic hormone-sensitive prostate cancer demonstrated improvement in overall
      survival with the addition of docetaxel chemotherapy or abiraterone acetate to
      standard androgen deprivation therapy. A single-arm phase 2 study of the PARP
      inhibitor olaparib demonstrated high response rates and more favorable
      progression-free and overall survival for men with metastatic castration
      resistant prostate cancer and DNA repair defects treated with olaparib compared
      with men without DNA repair defects. Multiple ongoing clinical trials are
      investigating novel hormonal therapies and combinations of chemotherapy, targeted
      small molecules, immunotherapy, and radiopharmaceuticals. Progress continues to
      be made in the treatment of metastatic prostate cancer, and ongoing clinical
      trials continue to investigate novel agents and approaches to treatment.

PMID- 29644452
TI  - Implications of non-accidental trauma on resource utilization and outcomes.
AB  - PURPOSE: The purpose was to compare the resource utilization and outcomes between
      patients with suspected (SUSP) and confirmed (CONF) non-accidental trauma (NAT).
      METHODS: The institutional trauma registry was reviewed for patients aged 0-18
      years presenting from 2007 to 2012 with a diagnosis of suspicion for NAT.
      Patients with suspected and confirmed NAT were compared. RESULTS: There were 281
      patients included. CONF presented with a higher heart rate (142 +/- 27 vs 128 +/-
      23 bpm, p < 0.01), lower systolic blood pressure (100 +/- 18 vs 105 +/- 16 mm Hg,
      p = 0.03), and higher Injury Severity Score (15 +/- 11 vs 9 +/- 5, p < 0.01).
      SUSP received fewer consultations (1.6 +/- 0.7 vs 2.4 +/- 1.1, 95% CI - 0.58 to -
      0.09, p < 0.01) and had a shorter length of stay (1.6 +/- 1.3 vs 7.8 +/- 9.8
      days, 95% CI - 4.58 to - 0.72, p < 0.01). SUSP were more often discharged home
      (OR 94.22, 95% CI: 21.26-417.476, p < 0.01). CONF had a higher mortality rate
      (8.2 vs 0%, p < 0.01). CONCLUSIONS: Patients with confirmed NAT present with more
      severe injuries and require more hospital resources compared to patients in whom
      NAT is suspected and ruled out.

PMID- 29644454
TI  - Letter to the Editor concerning: "Results of pectus excavatum correction using a
      minimally invasive approach with subxyphoid incision and three-point fixation".

PMID- 29644453
TI  - Analysis of factors predicting surgical intervention and associated costs in
      pediatric breast masses: a single center study.
AB  - PURPOSE: Finding a breast mass in a child provokes apprehension in parents,
      especially in those with a family history of breast cancer. Clinicians must
      decide between serial imaging or biopsy of the mass. Herein, we identify
      management differences in those with and without a positive family history, as
      well as identify cost differences. METHODS: An institutional retrospective review
      was performed of patients (2-18 years of age) with a diagnosis of breast mass.
      Patient demographics, presentation, medical and surgical history, physical exam,
      imaging, and pathologic diagnosis were collected. Cost data were acquired from
      the pediatric health information system (PHIS). Costs were compared between
      patients managed by biopsy versus serial ultrasounds. Bivariate analyses
      including Pearson's Chi-square, student's t tests, and logistic regression were
      performed. RESULTS: The probability of biopsy increases with age (p = 0.0001) and
      female gender (p = 0.006). Biopsy rate is higher for larger masses (p < 0.0001),
      growing size (p < 0.0001), and in patients with a positive family history of
      breast cancer (p < 0.0001). The average cost of care for management with initial
      excisional biopsy was $4491 versus those with serial ultrasounds ($986) (p <
      0.0001). CONCLUSIONS: In patients with small lesions, even with a family history
      of breast cancer, non-operative monitoring is a safe and cost-effective
      alternative to invasive biopsy.

PMID- 29644455
TI  - Neonatal independent predictors of severe NEC.
AB  - PURPOSE: Necrotizing enterocolitis (NEC) is a severe neonatal disease. The
      present study aimed to identify factors predisposing the development of severe
      forms of NEC. METHODS: This retrospective study examined NEC patients in a single
      centre between 2002 and 2015. Data concerning clinical characteristics,
      therapeutic management as well as short-term outcomes were collected. We compared
      the patients receiving successful medical treatment and those requiring surgical
      intervention. Patients who underwent surgery were distinguished in three
      subcategories. Bivariate and multivariate analyses were used for the statistical
      analysis. RESULTS: We identified 155 patients in the study period. 102 were
      treated conservatively and 53 required surgery. 8 received a primary peritoneal
      drainage, 31 received a drainage and a subsequent laparotomy and 14 received a
      laparotomy. Multivariate regression analysis identified a lower risk for surgery
      with a later onset and higher serum pH values, whereas an increased risk with
      higher C reactive Protein (CRP) levels at the onset. Pneumatosis intestinalis was
      identified as a protective factor. Overall mortality was 6.4%, with higher
      percentage in surgical NEC. CONCLUSION: This study suggests that a later onset is
      a protective sign for the progression to surgery, whereas lower pH values and
      higher CRP levels are prognostic factors associated with the need for surgery.
      The line of treatment involving explorative laparotomy in case of perforation
      seems to be rewarded by low morbidity and mortality rate.

PMID- 29644456
TI  - Genetic background effects in quantitative genetics: gene-by-system interactions.
AB  - Proper cell function depends on networks of proteins that interact physically and
      functionally to carry out physiological processes. Thus, it seems logical that
      the impact of sequence variation in one protein could be significantly influenced
      by genetic variants at other loci in a genome. Nonetheless, the importance of
      such genetic interactions, known as epistasis, in explaining phenotypic variation
      remains a matter of debate in genetics. Recent work from our lab revealed that
      genes implicated from an association study of toxin tolerance in Saccharomyces
      cerevisiae show extensive interactions with the genetic background: most
      implicated genes, regardless of allele, are important for toxin tolerance in only
      one of two tested strains. The prevalence of background effects in our study adds
      to other reports of widespread genetic-background interactions in model
      organisms. We suggest that these effects represent many-way interactions with
      myriad features of the cellular system that vary across classes of individuals.
      Such gene-by-system interactions may influence diverse traits and require new
      modeling approaches to accurately represent genotype-phenotype relationships
      across individuals.

PMID- 29644458
TI  - Erratum to: Development and Diseases of the Collecting Duct System.

PMID- 29644457
TI  - An interplay between Shugoshin and Spo13 for centromeric cohesin protection and
      sister kinetochore mono-orientation during meiosis I in Saccharomyces cerevisiae.
AB  - Meiosis is a specialized cell division process by which haploid gametes are
      produced from a diploid mother cell. Reductional chromosome segregation during
      meiosis I (MI) is achieved by two unique and conserved events: centromeric
      cohesin protection (CCP) and sister kinetochore mono-orientation (SKM). In
      Saccharomyces cerevisiae, a meiosis-specific protein Spo13 plays a role in both
      these centromere-specific events. Despite genome-wide association of Spo13, we
      failed to detect its function in global processes such as cohesin loading,
      cohesion establishment and homologs pairing. While Shugoshin (Sgo1) and protein
      phosphatase 2A (PP2ARts1) play a central role in CCP, it is not fully understood
      whether Spo13 functions in the process through a Sgo1- PP2ARts1-dependent or 
      independent mechanism. To delineate this and to find the relative contribution of
      each of these proteins in CCP and SKM, we meticulously observed the sister
      chromatid segregation pattern in the wild type, sgo1Delta, rts1Delta and
      spo13Delta single mutants and in their respective double mutants. We found that
      Spo13 protects centromeric cohesin through a Sgo1- PP2ARts1-independent
      mechanism. To our surprise, we observed a hitherto unknown role of Sgo1 in SKM.
      Further investigation revealed that Sgo1-mediated recruitment of aurora kinase
      Ipl1 to the centromere facilitates monopolin loading at the kinetochore during
      MI. Hence, this study uncovers the role of Sgo1 in SKM and demonstartes how the
      regulators (Sgo1, PP2ARts1, Spo13) work in a coordinated manner to achieve
      faithful chromosome segregation during meiosis, the failure of which leads to
      aneuploidy and birth defects.

PMID- 29644459
TI  - A phase II study of bevacizumab and irinotecan plus alternate-day S-1 as a second
      line therapy in patients with metastatic colorectal cancer: the AIRS study.
AB  - BACKGROUND: The aim of this single-arm phase II clinical trial was to evaluate
      whether the alternate-day administration of S-1 plus irinotecan would reduce the
      incidence of severe diarrhea in comparison to consecutive-day S-1 administration
      (standard IRIS regimen) in second-line treatment for patients with metastatic
      colorectal cancer. METHODS: Patients with metastatic colorectal cancer after
      failure with first-line treatment of oxaliplatin and fluoropyrimidine were
      enrolled. Irinotecan (150 mg/m2) and bevacizumab (5 mg/kg) were given
      intravenously on day 1. Oral S-1 was administered on alternate days at a dose of
      40-60 mg twice a day. Cycles were repeated every 2 weeks. The primary endpoint
      was the incidence of grade >= 3 diarrhea. Our hypothesis set 21% as a threshold
      incidence and 10% as an expected incidence from previous studies with one-sided
      alpha 0.05. The secondary endpoints included the relative dose intensity,
      progression-free survival, overall survival and other adverse events. RESULTS: A
      total of 51 patients were enrolled. The incidence of grade >= 3 diarrhea was
      15.7% (8/51). Other common grade >= 3 adverse events were neutropenia, anemia,
      thrombocytopenia and fatigue were 13.7% (7/51), 5.9% (3/51), 2.0% (1/51) and 5.9%
      (3/51), respectively. The relative dose intensities of irinotecan, bevacizumab,
      and S-1 were 80.0, 86.8, and 77.7%, respectively. The median progression-free
      survival and overall survival were 8.4 months (5.8-9.8) and 17.1 months (11.8
      22.3). CONCLUSIONS: The alternate-day S-1 administration does not have
      significant effectiveness to reduce diarrhea in patients who received second-line
      treatment for metastatic colorectal cancer.

PMID- 29644460
TI  - Phase II study of cisplatin/pemetrexed combined with bevacizumab followed by
      pemetrexed/bevacizumab maintenance therapy in patients with EGFR-wild advanced
      non-squamous non-small cell lung cancer.
AB  - PURPOSE: This phase II study was performed to evaluate the efficacy and safety of
      cisplatin/pemetrexed combined with 15 mg/kg of bevacizumab followed by
      pemetrexed/bevacizumab maintenance therapy as first-line chemotherapy in advanced
      non-squamous non-small cell lung cancer (NSCLC) limited to epidermal growth
      factor receptor (EGFR)-wild type. PATIENTS AND METHODS: Fifty patients with
      advanced or metastatic EGFR-wild type NSCLC aged < 75 years old were enrolled in
      the study. The patients were treated with four cycles of cisplatin (75 mg/m2, day
      1), pemetrexed (500 mg/m2, days 1), and bevacizumab (15 mg/kg, day 1), every 3
      weeks, followed by pemetrexed plus bevacizumab maintenance until progression for
      achieving a response over stable disease after induction chemotherapy. RESULTS:
      Partial response and stable disease were observed in 35 (objective response rate:
      70, 95% CI: 55.4-82.1%) and 9 patients, respectively, and 39 (78%) patients
      received pemetrexed plus bevacizumab maintenance therapy. Median progression-free
      survival and overall survival periods were 12.0 months (95% CI: 7.5-16.5 months)
      and 31.0 months (95% CI: 22.2-39.8 months), respectively. Grade 3 adverse events
      included neutropenia (14%), nausea (10%), anorexia (18%), and hypertension (8%).
      Coagulation disorder was observed in one patient, but all of these events were
      reversible and resulted in no treatment-related deaths. CONCLUSION: The
      combination of cisplatin/pemetrexed/bevacizumab followed by
      pemetrexed/bevacizumab maintenance therapy exhibited favorable efficacy and
      manageable toxicity profiles in patients with EGFR-wild type non-squamous NSCLC
      (UMIN-CTR number: UMIN000003645).

PMID- 29644461
TI  - 26th Congress of the European Society for Pediatric Neurosurgery (ESPN) Bonn
      Germany, 6-9 May 2018.

PMID- 29644464
TI  - Heavy metal enrichment and ecological risk assessment of surface sediments in
      Khorramabad River, West Iran.
AB  - The ecological health of rivers has often been threatened in urbanized catchments
      due to the expansion of industrial activities and the population growth.
      Khorramabad River which flows through Khorramabad city, west of Iran, is an
      example of such settings. The river water is used for agricultural purposes
      downstream. In this study, the effect of Khorramabad city on heavy metal and
      metalloid (Cu, Pb, Zn, Ni, Cr, and As) loads in Khorramabad River sediments was
      investigated. To evaluate sediment pollution and potential adverse biological
      effects, surface sediment samples were collected at selected locations along the
      river and were characterized for their geochemical properties. Contamination
      factor (CF), pollution load index (PLI), and ecological risk assessment (RI) were
      calculated. Also, sediment quality guidelines (SQGs) were used to screen
      contaminants of concern in the study area. The results showed that sediments were
      moderately polluted, with stations located in more densely populated areas
      showing higher pollution indicators. Copper, Zn, and Pb sources could be
      attributed to urban wastewater, whereas Ni, Cr, and As had both natural and
      anthropogenic sources. Moreover, ecological risk assessments showed that
      sediments could be classified in the category of low risk. The results of the
      present study showed the effect of anthropogenic activities on heavy metal loads
      of the river sediments and these findings can be used to mitigate potential
      impacts on the environment and human health.

PMID- 29644465
TI  - Impact of one-to-one tutoring on fundamentals of laparoscopic surgery (FLS)
      passing rate in a single center experience outside the United States: a
      randomized controlled trial.
AB  - BACKGROUND: Outside the US, FLS certification is not required and its teaching
      methods are not well standardized. Even if the FLS was designed as "stand alone"
      training system, most of Academic Institution offer support to residents during
      training. We present the first systematic application of FLS in Italy. Our aim
      was to evaluate the role of mentoring/coaching on FLS training in terms of the
      passing rate and global performance in the search for resource optimization.
      METHODS: Sixty residents in general surgery, obstetrics & gynecology, and urology
      were selected to be enrolled in a randomized controlled trial, practicing FLS
      with the goal of passing a simulated final exam. The control group practiced
      exclusively with video material from SAGES, whereas the interventional group was
      supported by a mentor. RESULTS: Forty-six subjects met the requirements and
      completed the trial. For the other 14 subjects no results are available for
      comparison. One subject for each group failed the exam, resulting in a passing
      rate of 95.7%, with no obvious differences between groups. Subgroup analysis did
      not reveal any difference between the groups for FLS tasks. CONCLUSION: We
      confirm that methods other than video instruction and deliberate FLS practice are
      not essential to pass the final exam. Based on these results, we suggest the
      introduction of the FLS system even where a trained tutor is not available. This
      trial is the first single institution application of the FLS in Italy and one of
      the few experiences outside the US. Trial Number: NCT02486575 (
      https://www.clinicaltrials.gov ).

PMID- 29644466
TI  - Minimally invasive esophagectomy attenuates the postoperative inflammatory
      response and improves survival compared with open esophagectomy in patients with
      esophageal cancer: a propensity score matched analysis.
AB  - BACKGROUND: Minimally invasive esophagectomy (MIE) for patients with esophageal
      cancer has recently spread worldwide. However, whether MIE is less invasive has
      not yet been fully evaluated. METHODS: We retrospectively analyzed data from 551
      patients who underwent curative esophagectomy for esophageal cancer from 2005 to
      2014: 145 patients underwent minimally invasive esophagectomy (MIE) and 406
      patients underwent open transthoracic esophagectomy (OE). We compared
      postoperative CRP levels with propensity score matching. In addition, long-term
      outcomes were also compared between the groups. RESULTS: Operative time was
      significantly longer, and intraoperative blood loss was significantly less in the
      MIE group compared with the OE group. Although the incidence of postoperative
      complications was similar between the 2 groups, postoperative serum CRP levels
      during the first 3 and 5 postoperative days and peak postoperative CRP levels
      were significantly lower after MIE versus OE (MIE vs. OE, median, 15.21 vs. 19.50
      mg/dl; P < 0.001). The MIE group had significantly more favorable disease-free
      survival (DFS) and overall survival (OS) rates than the OE group (3-year DFS
      rate, 81.7 vs. 69.3%, log-rank P = 0.021; 3-year OS rate, 89.9 vs. 79.2%, log
      rank P = 0.007). MIE was an independent prognostic factor for patients with
      esophageal cancer. The incidence of regional lymph node recurrence was lower in
      the MIE group. CONCLUSIONS: MIE significantly attenuated postoperative serum CRP
      levels compared with OE. MIE could contribute to improved survival.

PMID- 29644467
TI  - Proficiency-based preparation significantly improves FES certification
      performance.
AB  - BACKGROUND: The Fundamentals of Endoscopic Surgery (FES) certification has
      recently been mandated by the American Board of Surgery but best methods for
      preparing for the exam are lacking. Our previous work demonstrated a 40% pass
      rate for PGY5 residents in our program. The purpose of this study was to
      determine the effectiveness of a proficiency-based skills and cognitive
      curriculum for FES certification. METHODS: Residents who agreed to participate (n
      = 15) underwent an orientation session, followed by skills pre-testing using
      three previously described models (Trus, Operation targeting task, and Kyoto) as
      well as the actual FES skills exam (vouchers provided by the FES committee).
      Participants then trained to proficiency on all three models for the skills
      curriculum and completed the FES online didactic material for the cognitive
      curriculum. Finally, participants post-tested on the models and took the actual
      FES certification exam. Values are mean +/- SD; p < 0.05 was considered
      significant. RESULTS: Of 15 residents who participated, 8 (53%) passed the FES
      skills exam at baseline. Participants required 2.7 +/- 1.3 h to achieve
      proficiency on the models and approximately 3 h to complete the cognitive
      curriculum. At post-test, 14 (93%, vs. pre-test 53%, p = 0.041) passed the FES
      skills exam. 14 (93%) passed the FES cognitive exam and 13/15 (87%) passed both
      the skills and cognitive exam and achieved FES certification. CONCLUSIONS: Our
      traditional clinical endoscopy curricula were not sufficient for senior residents
      to pass the FES exam. Implementation of a proficiency-based flexible endoscopy
      curriculum using bench-top models and the FES online materials was feasible and
      effective for the majority of learners. Importantly, with a modest amount of
      additional training, 87% of our trainees were able to pass the FES examination,
      which represents a significant improvement for our program. We expect that
      additional refinements of this curriculum may yield even better results for
      preparing future residents for the FES examination.

PMID- 29644468
TI  - [Pharmacological treatment of osteoarthritis-related pain].
AB  - Joint pain due to osteoarthritis (OA) is often severe and disabling and affects a
      large proportion of the aging population impairing daily living and quality of
      life. Numerous pharmacological treatment approaches are available. Including
      major OA guidelines this review presents the current evidence of pharmacological
      therapies in OA-related pain and covers topical, oral and intraarticular
      treatment approaches. In patients with mild OA topical nonsteroidal
      antiinflammatory drugs (NSAIDs) can be recommended. Topical capsaicin can be used
      when other treatments are ineffective or contraindicated. In patients with
      moderate to severe OA oral NSAIDs are suggested at the lowest effective dose for
      the shortest possible duration to control symptoms. Importantly, drug-related
      side effects and gastrointestinal, cardiovascular and renal comorbidities need to
      be taken into account. In patients with multiple-joint OA and high risk of NSAID
      induced adverse events duloxetine can be considered. The evidence of metamizole,
      symptomatic slow-acting drugs in osteoarthritis and other nutritional supplements
      in the treatment of OA pain is uncertain and the use of opioids is not routinely
      recommended. In patients suffering from severe OA-related pain intraarticular
      injections with glucocorticoids can be suggested to achieve short-term pain
      relief. Evidence for interventional approaches using hyaluronic acid or platelet
      rich plasma is uncertain. Yet, the efficacy of pharmacological therapies in OA
      related pain is often inconsistent and severe adverse events might occur. Thus,
      critical use of the different treatment options considering patient-related
      comorbidities and nonpharmacological therapies is of major importance.

PMID- 29644469
TI  - [Cognitive bias research and depression in chronic pain].
AB  - Chronic back pain is of enormous health and economic relevance for industrialized
      countries because a small group of patients with chronic disease is responsible
      for a large proportion of medical costs. The prevention of chronic disease is
      therefore a primary goal in the treatment of patients with acute low back pain.
      Psychological factors are the central risk factors for later chronification.
      Above all, especially depressive symptoms and occupational distress, as well as
      various maladaptive forms of pain management are central risk factors. It remains
      unclear which exact cognitive mechanisms are involved in the maintenance and
      reinforcement of depression and pain-related disability. In this review, the
      current results of cognitive bias research and theoretical models are presented
      and summarized regarding the relationship between chronic pain and depression.
      Finally, the clinical implications and recommendations for clinical research will
      be presented.

PMID- 29644471
TI  - Assessment of psychological distress among Asian adolescents and young adults
      (AYA) cancer patients using the distress thermometer: a prospective, longitudinal
      study.
AB  - PURPOSE: Since few studies have investigated whether the Distress Thermometer
      (DT) in Asian adolescent and young adult (AYA) cancer patients (between 15 and 39
      years), we investigated the appropriateness of the DT as a screening tool for
      psychological symptom burden in these AYA patients and to evaluate AYA patients'
      distress across a trajectory of three time points longitudinally over a 6-month
      period. METHODS: This was a prospective, longitudinal study. Recruited Asian AYA
      patients were diagnosed with lymphomas, sarcomas, primary brain malignancies, or
      germ cell tumors. Patients completed the DT, PedsQL Generic Core Scales, and the
      Rotterdam Symptom Checklist. Data were analyzed using STATA version 15. RESULTS:
      Approximately half of the patients experienced clinically significant DT distress
      (distress score >= 4) early in their cancer journey with 43.1% patients
      presenting with distress at time of diagnosis and 47.7% patients 1 month after
      diagnosis. Among AYA patients > 24 years old, worry (68.3%), insurance/financial
      issues (61%), treatment decisions (43.9%), work/school issues (41.5%),
      nervousness (41.5%), and sadness (41.5%) were the top five identified problems.
      On the other hand, the top five identified problems among AYA <= 24 years were
      worry (54.2%), nervousness (41.7%), bathing/dressing problems (37.5%),
      work/school issues (33.3%), and fatigue (33.3%). DT scores were significantly
      associated with certain psychological symptom burden items such as worry (p <
      0.001), depressed mood (p = 0.020), and nervousness (p = 0.015). CONCLUSION: The
      DT is a useful screening tool for psychological distress in AYA cancer patients
      with clinically significant distress being identified in the early phases of the
      cancer journey.

PMID- 29644470
TI  - Ruthenium(II)-N-alkyl phenothiazine complexes as potential anticancer agents.
AB  - In recent years, the search for effective anticancer compounds based on
      transition metal complexes has been the focus of medical investigations. The
      synergy between the ruthenium(II) and N-alkylphenothiazine counter-ions
      (chlorpromazine hydrochloride, thioridazine hydrochloride and trifluoperazine
      dihydrochloride, respectively) through the formation of three different complexes
      (1-3) was investigated. We explored whether the selected counter-ions and
      complexes might affect redox homeostasis and genome integrity of normal human
      blood cells, and induce an inhibition of Na+/K+-ATPase and AChE at
      pharmacologically relevant doses. Our results have shown that counter-ions and
      complexes did not affect the activity of Na+/K+-ATPase, while AChE activity was
      inhibited in a dose-dependent manner. All investigated compounds disturbed the
      viability and redox homeostasis of lymphocytes. Complexes 1 and 2 displayed
      potent cytotoxic and prooxidant action while complex 3 behaved as a weaker
      genotoxic inducer. Still, the tested complexes appeared to be less genotoxic and
      more cytostatic than the corresponding counter-ions. The effects of selected
      complexes were also tested in PC12 and U2OS cancer cells with special attention
      being given to the ability of phenothiazines to affect dopamine D2 receptors.
      Using the confocal laser scanning microscopy, we observed that all the complexes
      reduced cell viability. Although all investigated complexes have been bound to
      the dopamine receptor D2-eGFP, only complex 3 reduced its surface density and
      increased its lateral mobility in investigated cell lines. Albeit the role of
      alternative targets for complex 3 cannot be ruled out, its effects should be
      further examined as potential treatment strategy against cancer cells that
      overexpress D2.

PMID- 29644472
TI  - Pictorial Representation of Illness and Self Measure-Revised 2 (PRISM-R2): an
      effective tool to assess perceived burden of thyroid cancer in mainland China.
AB  - PURPOSE: Thyroid cancer, especially differentiated thyroid cancer (DTC), is a
      highly prevalent chronic disease that is known to cause considerable distress,
      related both to the high recurrence and treatment of the disease. The Pictorial
      Representation of Illness and Self Measure-Revised 2 (PRISM-R2) has been
      developed as a visual measure to assess suffering. The aim of this study was to
      evaluate the ability of the instrument to identify patients with DTC with
      different levels of suffering who may need additional support care. METHODS:
      Participants were 338 adult inpatients with DTC who were accepting the
      radioiodine for remnant ablation in the nuclear medicine department. The
      assessment tools included the following: (1) the PRISM-R2, yielding Self-Illness
      Separation (SIS) and Illness Perception Measure (IPM); (2) distress thermometer
      (DT), a measure of thyroid cancer-related distress; (3) posttraumatic growth
      inventory (PTGI); (4) 12-item Short-Form health survey (SF-12); and (5) the
      Supportive Care Needs Survey Short Form (SCNS-SF34). In addition, the content
      validity of PRISM-R2 was tested using the patients' comments. RESULTS: SIS and
      IPM showed medium intercorrelation (r = -.482; p < 0.01), and both of them showed
      strongly significant associations with DT. SIS also showed significant
      correlations with one factor of PTGI (personal strength), four factors of SF-12
      (general health, role-emotional, mental health, and vitality), and one factor of
      SCNS-SF34 (psychological needs). IPM showed significant correlations with five
      factors of SF-12 and all the factors of SCNS-SF34. No correlation was found
      between IPM and PTGI. CONCLUSIONS: PRISM-R2 is a well-accepted and understandable
      tool to assess the psychological burden of patients with thyroid cancer in
      Chinese settings. It may be useful to guide or evaluate the interventions for the
      patients.

PMID- 29644473
TI  - Attention and executive functions computer training for attention
      deficit/hyperactivity disorder (ADHD): results from a randomized, controlled
      trial.
AB  - Multicenter randomized clinical superiority single-blind trial investigated the
      effect of a computer training program targeting multiple cognitive functions.
      Seventy children with ADHD, aged 6-13, were randomized to intervention or control
      group. The intervention group used ACTIVATETM for 8 weeks and both groups
      received treatment as usual and were assessed in regard to cognitive functions,
      symptoms, behavioral and functional outcome measures after 8, 12 and 24 weeks.
      There was no significant effect on the primary outcome, sustained attention (beta
      = - 0.047; CI - 0.247 to 0.153) or the secondary outcomes [parent-rated ADHD-RS,
      beta = - 0.037; CI (- 0.224 to 0.150); teacher-rated-ADHD-RS, beta = 0.093; CI (-
      0.107 to 0.294); parent-rated-BRIEF, beta = - 0.119; CI (- 0.307 to 0.069); and
      teacher-rated-BRIEF, beta = 0.136; CI (- 0.048 to 0.322)]. This multicenter
      randomized clinical trial found no significant beneficial effects of cognitive
      training using the computer program ACTIVATE on the primary or secondary outcome
      measures in children with ADHD. Nevertheless, our study was likely underpowered
      to detect small to moderate changes.Trial registration ClinicalTrials.gov:
      NCT01752530, date of registration: December 10, 2012.

PMID- 29644474
TI  - Risk factors for parental psychopathology: a study in families with children or
      adolescents with psychopathology.
AB  - The parents of children with psychopathology are at increased risk for
      psychiatric symptoms. To investigate which parents are mostly at risk, we
      assessed in a clinical sample of families with children with psychopathology,
      whether parental symptom scores can be predicted by offspring psychiatric
      diagnoses and other child, parent and family characteristics. Parental
      depressive, anxiety, avoidant personality, attention-deficit/hyperactivity
      (ADHD), and antisocial personality symptoms were measured with the Adult Self
      Report in 1805 mothers and 1361 fathers of 1866 children with a psychiatric
      diagnosis as assessed in a child and adolescent psychiatric outpatient clinic. In
      a multivariate model, including all parental symptom scores as outcome variables,
      all offspring psychiatric diagnoses, offspring comorbidity and age, parental age,
      parental educational attainment, employment, and relationship status were
      simultaneously tested as predictors. Both 35.7% of mothers and 32.8% of fathers
      scored (sub)clinical for at least one symptom domain, mainly depressive symptoms,
      ADHD symptoms or, only in fathers, avoidant personality symptoms. Parental
      psychiatric symptoms were predicted by unemployment. Parental depressive and ADHD
      symptoms were further predicted by offspring depression and offspring ADHD,
      respectively, as well as by not living together with the other parent. Finally,
      parental avoidant personality symptoms were also predicted by offspring autism
      spectrum disorders. In families with children referred to child and adolescent
      psychiatric outpatient clinics, parental symptom scores are associated with
      adverse circumstances and with similar psychopathology in their offspring. This
      signifies, without implying causality, that some families are particularly
      vulnerable, with multiple family members affected and living in adverse
      circumstances.

PMID- 29644475
TI  - Electrophysiologic Toxicity of Chemoradiation.
AB  - PURPOSE OF REVIEW: There is growing awareness of the link between oncology
      treatments and cardiovascular (CV) complications. This has led to the development
      of cardio-oncology, a specialty aimed at managing CV risk and disease in cancer
      patients and survivors. Cardiac arrhythmias are potential adverse CV
      complications of cancer treatments; however, these cardiotoxicities are often
      underappreciated due to the uncertain arrhythmogenic mechanisms of various
      chemotherapeutic agents. RECENT FINDINGS: Chemotherapeutic agents can induce
      arrhythmias via direct electrophysiological effects on ion channels or
      intracellular signaling pathways, or indirectly from cardiac tissue damage. As
      more drugs are being linked to the development of arrhythmias, a deeper
      understanding of the pathophysiology of their electrophysiological (EP) effects
      will be necessary. Expanding research in this field has allowed for the
      identification of novel agents with potential arrhythmogenic properties and the
      development of preventative measures, early recognition, and closer surveillance
      of patients more susceptible to these EP side effects.

PMID- 29644476
TI  - Reconstructive Management Pearls for the Transgender Patient.
AB  - PURPOSE OF REVIEW: A growing number of transgender patients are seeking gender
      affirming genital reconstructive surgery (GRS). These complex procedures have
      high complication rates. We describe common surgical pitfalls in GRS and
      approaches for minimizing complications. RECENT FINDINGS: Penile inversion
      vaginoplasty has been associated with excellent cosmetic and functional outcomes.
      A robotic-assisted dissection may minimize risk of rectal injury. As a younger
      transgender population chooses pubertal suppression, alternative sources for
      lining the vaginal canal, such as enteric vaginoplasties, may be more widely
      utilized. Since adoption of microvascular techniques in phalloplasty,
      transmasculine individuals have potential for a sensate neophallus and
      penetrative intercourse. Urethral complications are common and challenging to
      manage; techniques using flap coverage may minimize ischemia-related strictures.
      Innovations in prosthesis placement require adaptations to neophallus anatomy. A
      growing number of transgender individuals are seeking genital reconstruction.
      Ongoing innovation in surgical technique is needed to improve patient outcomes.

PMID- 29644477
TI  - The Selective Use of Radiation Therapy in Rectal Cancer Patients.
AB  - PURPOSE OF REVIEW: Colorectal cancer has a high global incidence, and standard
      treatment employs a multimodality approach. In addition to cure, minimizing
      treatment-related toxicity and improving the therapeutic ratio is a common goal.
      The following article addresses the potential of omitting radiotherapy in select
      rectal cancer patients. RECENT FINDINGS: Omission of radiotherapy in rectal
      cancer is analyzed in the context of historical findings, as well as more recent
      data describing risk stratification of stage II-III disease, surgical
      optimization, imaging limitations, improvement in systemic chemotherapeutic
      agents, and contemporary studies evaluating selective omission of radiotherapy. A
      subset of rectal cancer patients exists that may be considered low to
      intermediate risk for locoregional recurrence. With appropriate staging, surgical
      technique, and possibly improved systemic therapy, it may be feasible to
      selectively omit radiotherapy in these patients. Current imaging limitations as
      well as evidence of increased locoregional recurrence following radiotherapy
      omission lend us to continue supporting the standard treatment of approach of
      neoadjuvant chemoradiation therapy followed by surgical resection until
      additional improvements and prospective evidence can support otherwise.

PMID- 29644478
TI  - Reconstruction of Membranous Urethral Strictures.
AB  - PURPOSE OF REVIEW: Due to the proximity of the rhabdosphincter and cavernous
      nerves to the membranous urethra, reconstruction of membranous urethral stricture
      implies a risk of urinary incontinence and erectile dysfunction. To avoid these
      complications, endoscopic management of membranous urethral strictures is
      traditionally favored, and bulboprostatic anastomosis is reserved as the main
      classical approach for open reconstruction of recalcitrant membranous urethral
      stricture. The preference for the anastomotic urethroplasty among reconstructive
      urologists is likely influenced by the familiarity and experience with trauma
      related injuries. We review the literature focusing on the anatomy of membranous
      urethra and on the evolution of treatments for membranous urethral strictures.
      RECENT FINDINGS: Non-traumatic strictures affecting bulbomembranous urethra are
      typically sequelae of instrumentation, transurethral resection of the prostate,
      prostate cancer treatment, and pelvic irradiation. Being a different entity from
      trauma-related injuries where urethra is not in continuity, a new understanding
      of membranous urethral anatomy is necessary for the development of novel
      reconstruction techniques. Although efficacious and durable to achieve urethral
      patency, classical bulboprostatic anastomosis carries a risk of de-novo
      incontinence and impotence. Newer and relatively less invasive reconstructive
      alternatives include bulbar vessel-sparing intra-sphincteric bulboprostatic
      anastomosis and buccal mucosa graft augmented membranous urethroplasty
      techniques. The accumulated experience with these techniques is relatively
      scarce, but several published series present promising results. These approaches
      are especially indicated in patients with previous transurethral resection of the
      prostate in which sparing of rhabdosphincter and the cavernous nerves is
      important in attempt to preserve continence and potency. Additionally,
      introduction of buccal mucosa onlay grafts could be especially beneficial in
      radiation-induced strictures to avoid transection of the sphincter in continent
      patients, and to preserve the blood supply to the urethra for incontinent
      patients who will require artificial urinary sphincter placement. The evidence
      regarding erectile functional outcomes is less solid and this item should be
      furtherly investigated.

PMID- 29644480
TI  - Correction to: Microleakage in class V composite and compomer restorations
      following exposure to a colutory prescribed for the treatment of xerostomy.
AB  - In the original publication of the article, one of the author names was published
      incorrectly as Jose L. Calvo. The correct name is Jose L. Calvo-Guirado.

PMID- 29644479
TI  - Design of a sustainable prepolarizing magnetic resonance imaging system for
      infant hydrocephalus.
AB  - OBJECTIVES: The need for affordable and appropriate medical technologies for
      developing countries continues to rise as challenges such as inadequate energy
      supply, limited technical expertise, and poor infrastructure persist. Low-field
      magnetic resonance imaging (LF MRI) is a technology that can be tailored to meet
      specific imaging needs within such countries. Its low power requirements and the
      possibility of operating in minimally shielded or unshielded environments make it
      especially attractive. Although the technology has been widely demonstrated over
      several decades, it is yet to be shown that it can be diagnostic and improve
      patient outcomes in clinical applications. We here demonstrate the robustness of
      prepolarizing MRI (PMRI) technology for assembly and deployment in developing
      countries for the specific application to infant hydrocephalus. Hydrocephalus
      treatment planning and management requires only modest spatial resolution, such
      that the brain can be distinguished from fluid-tissue contrast detail within the
      brain parenchyma is not essential. MATERIALS AND METHODS: We constructed an
      internally shielded PMRI system based on the Lee-Whiting coil system with a 22-cm
      diameter of spherical volume. RESULTS: In an unshielded room, projection phantom
      images were acquired at 113 kHz with in-plane resolution of 3 mm * 3 mm, by
      introducing gradient fields of sufficient magnitude to dominate the 5000 ppm
      inhomogeneity of the readout field. DISCUSSION: The low cost, straightforward
      assembly, deployment potential, and maintenance requirements demonstrate the
      suitability of our PMRI system for developing countries. Further improvement in
      image spatial resolution and contrast of LF MRI will broaden its potential
      clinical utility beyond hydrocephalus.

PMID- 29644481
TI  - Efficacious Cefazolin Prophylactic Dose for Morbidly Obese Women Undergoing
      Bariatric Surgery Based on Evidence from Subcutaneous Microdialysis and
      Populational Pharmacokinetic Modeling.
AB  - PURPOSE: To determine the efficacious cefazolin prophylactic dose for bariatric
      surgery using free subcutaneous concentrations accessed by microdialysis after 2
      g or 3 g i.v. bolus dosing to morbidly obese women and POPPK modeling. METHODS: A
      POPPK model with variable plasma and subcutaneous tissue protein binding was
      developed to simultaneously describe plasma and tissue data sets. The outcomes
      was predicted for common surgical site infection (SSI) bacteria over 3, 4, 5 and
      6 h periods postdose, as probability of target attainment (PTA) using Monte Carlo
      simulation. RESULTS: CFZ 2 g warrant up to 5 h SSI prophylaxis for bacteria with
      MICs <=1 mg/L such as Escherichia coli and Staphylococcus aureus. For species
      such as Klebsiella pneumoniae, which present MIC distribution frequency of 2
      mg/L, the maintenance of PTA >= 90% occurs with a 3 g dose for surgeries lasting
      up to 5 h, and 2 g dose provide an adequate response up to 4 h (PTA of 89%).
      CONCLUSIONS: Effectiveness of CFZ 2 g is similar to 3 g against bacteria with a
      MIC up to 2 mg/L, especially if the surgery does not last for more than 4 h.

PMID- 29644483
TI  - Studies of abnormalities of the lower esophageal sphincter during esophageal
      emptying based on a fully coupled bolus-esophageal-gastric model.
AB  - The aim of this work was to develop a fully coupled bolus-esophageal-gastric
      model based on the immersed boundary-finite element method to study the process
      of esophageal emptying across the esophagogastric junction (EGJ). The model
      included an esophageal segment, an ellipsoid-shaped stomach, a bolus, and a
      simple model of the passive and active sphincteric functions of the lower
      esophageal sphincter (LES). We conducted three sets of case studies: (1) the
      effect of a non-relaxing LES; (2) the influence of the tissue anisotropy in the
      form of asymmetrical right- and left-sided compliance of the LES segment; and (3)
      the influence of LES and gastric wall stiffness on bulge formation of the distal
      esophageal wall. We found that a non-relaxing LES caused sustained high wall
      stress along the LES segment and obstruction of bolus emptying. From the
      simulations of tissue anisotropy, we found that the weaker side (i.e., more
      compliant) of the LES segment sustained greater deformation, greater wall shear
      stress, and a greater high-pressure load during bolus transit. In the third set
      of studies, we found that a right-sided bulge in the esophageal wall tends to
      develop during esophageal emptying when LES stiffness was decreased or gastric
      wall stiffness was increased. Hence, the bulge may be partly due to the
      asymmetric configuration of the gastric wall with respect to the esophageal tube.
      Together, the observations from these simulations provide insight into the
      genesis of epiphrenic diverticula, a complication observed with esophageal
      motility disorders. Future work, with additional layers of complexity to the
      model, will delve into the mechanics of gastroesophageal reflux and the effects
      of hiatus hernia on EGJ function.

PMID- 29644484
TI  - Intracranial control and survival outcome of tyrosine kinase inhibitor (TKI)
      alone versus TKI plus radiotherapy for brain metastasis of epidermal growth
      factor receptor-mutant non-small cell lung cancer.
AB  - INTRODUCTION: The efficacy of tyrosine kinase inhibitors (TKIs) with and without
      radiotherapy (RT) has not been determined in patients with brain metastases from
      epidermal growth factor receptor-mutant TKI naive non-small cell lung cancer
      (NSCLC). METHODS: Between 2008 and 2016, 586 patients were diagnosed with NSCLC
      and treated with TKIs at a hospital in Seoul, South Korea; 81 of these patients
      met the eligibility criteria for our study. Outcomes analyzed included
      intracranial progression (ICP), neurological death, and overall survival (OS).
      RESULTS: The 2-year cumulative incidence of ICP was 36.5% in the TKI plus RT
      group and 62.2% in the TKI alone group (P = 0.006). The chronological pattern
      analysis indicated that 64.3% of ICP developed within 12 months of the start of
      TKI treatment in the TKI alone group. The multivariate analysis revealed that
      treatment group (P = 0.003) and duration of TKI treatment <= 12 months (P <
      0.001) were significantly associated with ICP. However, no significant
      differences were observed in the 2-year OS rate (P = 0.267) or the 2-year
      cumulative incidence of neurological death (P = 0.740). CONCLUSIONS: Cumulative
      incidence of ICP was significantly lower with TKI plus RT than with TKI alone;
      however, there was no significant difference in OS or neurological death.
      Deferring brain RT may not compromise neurologic and survival outcome in selected
      patients, but close magnetic resonance imaging follow-up is recommended for
      patients who defer brain RT.

PMID- 29644482
TI  - Metabolic syndrome and the decreased levels of uric acid by leflunomide favor
      redox imbalance in patients with rheumatoid arthritis.
AB  - Oxidative stress plays a role in the pathophysiology of rheumatoid arthritis
      (RA). The aim of the present study was to verify the influence of metabolic
      syndrome (MetS) and disease-modifying antirheumatic drugs on nitrosative and
      oxidative biomarkers in patients with RA. A total of 177 patients with RA and 150
      healthy volunteers participated in this study, which measured lipid
      hydroperoxides, advanced oxidation protein products (AOPP), nitric oxide
      metabolites (NOx), carbonyl protein, total radical-trapping antioxidant parameter
      (TRAP), uric acid (UA), and C-reactive protein (CRP). NOx and the NOx/TRAP ratio
      were significantly increased in RA, while no significant differences in lipid
      hydroperoxides, AOPP, UA, and TRAP levels were found between both groups.
      Treatment with leflunomide was associated with increased levels of carbonyl
      protein, and lowered levels in TRAP and UA, while the NOx/TRAP ratio further
      increased. NOx and the NOx/TRAP ratio were significantly higher in women than in
      men, while TRAP and UA were significantly lower in women. MetS was accompanied by
      increased AOPP and UA levels. RA was best predicted by increased NOx/TRAP ratio,
      CRP, and BMI. In conclusion, our data demonstrated that NOx and NOx/TRAP are
      strongly associated with RA physiopathology. Our findings suggest that inhibition
      of iNOS may become an interesting therapeutic approach for the treatment of RA.
      In addition, the presence of MetS and a decrease in levels of UA by leflunomide
      favor redox imbalance in RA patients. More studies are needed to evaluate the
      impact of antioxidant capacity reduction on RA progression.

PMID- 29644485
TI  - Acceptance and compliance of TTFields treatment among high grade glioma patients.
AB  - BACKGROUND: Tumor treating fields (TTFields) significantly prolong both
      progression-free and overall survival in patients with newly diagnosed
      glioblastoma (GBM). TTFields are delivered to the brain tumor via skin transducer
      arrays and should be applied for a minimum of 18 h per day (>= 75% compliance).
      This may cause limited acceptance by patients because of obstacles in daily
      routine. So far, there are limited data on factors influencing therapy acceptance
      and compliance. METHODS: In this retrospective study, fourty-one patients with
      primary GBM or recurrent high grade glioma (rHGG) have been treated with TTFields
      in our department. Compliance reports were generated at the monthly routine check
      of the device. We investigated demographic data, stage of disease and therapy
      duration in regard to treatment compliance. RESULTS: Thirty percent of patients
      with primary diagnosis of GBM were informed about TTFields. Acceptance rate among
      these patients was 36%. In this study, TTFields were prescribed in newly
      diagnosed GBM patients (57%) and in rHGG. Mean treatment compliance was 87% in
      the total population independent of age, sex and stage of disease. Compliance was
      not negatively correlated with time on treatment. CONCLUSION: TTFields are
      effective in newly diagnosed GBM, therefore acceptance and compliance is
      important for GBM treatment. We experienced moderate acceptance rate for
      TTFields, which is influenced by factors such as social support, comorbidities
      and independence in daily life. Overall therapy compliance lies above 75% and is
      not influenced by age, sex, stage of disease or duration of therapy. Improved
      patient consultation strategies will increase acceptance and compliance for
      better outcome.

PMID- 29644486
TI  - Analysis and forecasting of municipal solid waste in Nankana City using geo
      spatial techniques.
AB  - The objective of this study was to analyze and forecast municipal solid waste
      (MSW) in Nankana City (NC), District Nankana, Province of Punjab, Pakistan. The
      study is based on primary data acquired through a questionnaire, Global
      Positioning System (GPS), and direct waste sampling and analysis. Inverse
      distance weighting (IDW) technique was applied to geo-visualize the spatial trend
      of MSW generation. Analysis revealed that the total MSW generated was 12,419,636
      kg/annum (12,419.64 t) or 34,026.4 kg/day (34.03 t), or 0.46 kg/capita/day
      (kg/cap/day). The average wastes generated per day by studied households,
      clinics, hospitals, and hotels were 3, 7.5, 20, and 15 kg, respectively. The
      residential sector was the top producer with 95.5% (32,511 kg/day) followed by
      commercial sector 1.9% (665 kg/day). On average, high-income and low-income
      households were generating waste of 4.2 kg/household/day (kg/hh/day) and 1.7
      kg/hh/day, respectively. Similarly, large-size families were generating more (4.4
      kg/hh/day) waste than small-size families (1.8 kg/hh/day). The physical
      constituents of MSW generated in the study area with a population of about 70,000
      included paper (7%); compostable matter (61%); plastics (9%); fine earth, ashes,
      ceramics, and stones (20.4%); and others (2.6%).The spatial trend of MSW
      generation varies; city center has a high rate of generation and towards
      periphery generation lowers. Based on the current population growth and MSW
      generation rate, NC is expected to generate 2.8 times more waste by the year
      2050.This is imperative to develop a proper solid waste management plan to reduce
      the risk of environmental degradation and protect human health. This study
      provides insights into MSW generation rate, physical composition, and forecasting
      which are vital in its management strategies.

PMID- 29644487
TI  - Therapeutic use of carbohydrate-restricted diets in an autistic child; a case
      report of clinical and 18FDG PET findings.
AB  - The ketogenic diet (KD) is a high-fat, adequate-protein, and low-carbohydrate
      diet that has been used successfully in the treatment of refractory epilepsies
      for almost 100 years. There has been accumulating evidence to show that the KD
      may provide a therapeutic benefit in autism spectrum disorders, albeit by a yet
      unknown mechanism. We report a case of a 6-year-old patient with high-functioning
      autism and subclinical epileptic discharges who responded poorly to several
      behavioural and psychopharmacological treatments. The patient was subsequently
      placed on the KD due to significant glucose hypometabolism in the brain as
      revealed by an 18FDG PET. As soon as one month after starting the KD, the
      patient's behavior and intellect improved (in regard to hyperactivity, attention
      span, abnormal reactions to visual and auditory stimuli, usage of objects,
      adaptability to changes, communication skills, fear, anxiety, and emotional
      reactions); these improvements continued until the end of the observation period
      at 16 months on the KD. The 18FDG PET, measured at 12 months on the KD, revealed
      that 18F-FDG uptake decreased markedly and diffusely in the whole cerebral cortex
      with a relatively low reduction in basal ganglia in comparison to the pre-KD
      assessment. It warrants further investigation if the 18FDG PET imaging could
      serve as a biomarker in identifying individuals with autism who might benefit
      from the KD due to underlying abnormalities related to glucose hypometabolism.

PMID- 29644488
TI  - Brain ischemic preconditioning protects against moderate, not severe, transient
      global cerebral ischemic injury.
AB  - Ischemic preconditioning (IPC) in the brain increases ischemic tolerance to
      subsequent ischemic insults. In this study, we examined whether IPC protects
      neurons and attenuates microgliosis or not in the hippocampus following severe
      transient global cerebral ischemia (TCI) in gerbils. Gerbils were assigned to 8
      groups; 5- and 15-min sham operated groups, 5-min and 15-min TCI operated groups,
      IPC plus 5- and 15-min sham operated groups, and IPC plus 5- and 15-min TCI
      operated groups. IPC was induced by subjecting animals to 2-min transient
      ischemia 1 day before 5-min TCI for a typical transient ischemia and 15-min TCI
      for severe transient ischemia. Neuronal damage was examined by cresyl violet
      staining and Fluoro-Jade B histofluorescence staining. In addition, microglial
      activation was examined using immunohistochemistry for Iba-1 (a marker for
      microglia). Delayed neuronal death and microgliosis was found in the CA1 alone in
      the 5-min TCI operated group at 5 days post-ischemia, and, in the 15-min TCI
      operated group, neuronal death and microgliosis was shown in all CA areas (CA1-3)
      and the dentate gyrus. IPC displayed neuroprotection and attenuated microglial
      activation in the 5-min TCI operated group. However, in the 15-min TCI operated
      group, IPC did not show neuroprotection and not attenuate microglial activation.
      Our present findings indicate that IPC hardly protect against severe transient
      cerebral ischemic injury.

PMID- 29644489
TI  - An efficient protocol for the synthesis of highly sensitive indole imines
      utilizing green chemistry: optimization of reaction conditions.
AB  - Novel and highly sensitive indole-based imines have been synthesized. Their
      synthesis has been compared employing a variety of protocols. Ultimately, a
      convenient, economical and high yielding set of conditions employing green
      chemistry have been designed for their synthesis.

PMID- 29644490
TI  - Emerging Role of Immunotherapy in Advanced Urothelial Carcinoma.
AB  - PURPOSE OF REVIEW: Advanced urothelial carcinoma (aUC) has long been treated
      preferably with cisplatin-based chemotherapy, but many patients are cisplatin
      ineligible whereas for those who progress on a platinum-based regimen treatment
      options are limited. We review key recent data regarding immune checkpoint
      inhibitors that are changing this treatment landscape. RECENT FINDINGS: Since May
      2016, five different agents targeting the PD-1/PD-L1 pathway (atezolizumab,
      pembrolizumab, nivolumab, avelumab, durvalumab) have received FDA approval for
      the treatment of aUC in the platinum-refractory setting, while pembrolizumab and
      atezolizumab are FDA-approved for cisplatin-ineligible patients in the first-line
      setting. Clinical outcomes and safety profiles of these agents appear relatively
      comparable across separate trials; however, only pembrolizumab is supported by
      level I evidence from a large randomized phase III trial showing overall survival
      benefit over conventional cytotoxic salvage chemotherapy in the platinum
      refractory setting. Pembrolizumab has the highest level of evidence in platinum
      refractory aUC, whereas pembrolizumab and atezolizumab have comparable level of
      evidence in the frontline setting in cisplatin-ineligible patients. Ongoing
      research is evaluating novel agents, various rational combinations, and
      sequences, as well as predictive and prognostic biomarkers.

PMID- 29644491
TI  - Update on PARP Inhibitors in Breast Cancer.
AB  - OPINION STATEMENT: The single agent activity of PARP inhibitors (PARPi) in
      germline BRCA mutated (gBRCAm) breast and ovarian cancer suggests untapped
      potential for this new class of drug in breast cancer. The US Food and Drug
      Administration has approved three PARPi (olaparib, rucaparib, and niraparib) so
      far to treat certain ovarian cancers, including those with gBRCAm and olaparib
      for treatment of gBRCAm breast cancers. Several PARPi are now under clinical
      development for breast cancer in the various treatment settings. Recently, two
      phase III trials of olaparib (OlympiaD) and talazoparib (EMBRACA) demonstrated 3
      month progression-free survival improvement with PARPi compared to physician's
      choice single agent chemotherapy in metastatic gBRCAm breast cancer. To date,
      PARPi seems less efficacious in metastatic breast cancer patients than those with
      BRCA mutated platinum-sensitive recurrent ovarian cancer, perhaps reflecting the
      biologic heterogeneity and low somatic BRCA mutation rate in breast cancer. The
      use of PARPi is gradually evolving, including combination strategies with
      chemotherapy, targeted agents, radiotherapy, or immunotherapy in women with and
      without gBRCAm. The role of predictive biomarkers, including molecular signatures
      and homologous recombination repair deficiency scores based on loss of
      heterozygosity and other structural genomic aberrations, will be crucial to
      identify a subgroup of patients who may have benefit from PARPi. An improved
      understanding of the mechanisms underlying PARPi clinical resistance will also be
      important to enable the development of new approaches to increase efficacy. This
      is a field rich in opportunity, and the coming years should see a better
      understanding of which breast cancer patients we should treat with PARPi and
      where these agents should come in over the course of treatment.

PMID- 29644493
TI  - Exploring the Correlates of Linkage to HIV Medical Care Among Persons Living with
      HIV Infection (PLWH) in the Deep South: Results and Lessons Learned from the
      Louisiana Positive Charge Initiative.
AB  - We explored the correlates of linkage to HIV medical care and barriers to HIV
      care among PLWH in Louisiana. Of the 998 participants enrolled, 85.8% were
      successfully linked to HIV care within 3 months. The majority of participants
      were male (66.2%), African American (81.6%), and had limited education (74.4%).
      Approximately 22% of participants were Black gay and bisexual men. The most
      common reported barrier to care was lack of transportation (27.1%). Multivariable
      analysis revealed that compared with Black gay and bisexual men, White gay and
      bisexual men were significantly more likely to be linked to HIV care (adjusted
      prevalence ratio, aPR 1.08, 95% CI 1.02-1.13). Additionally, participants
      reporting moderate to high levels of stigma at intake (p < 0.05) were
      significantly more likely to be linked to HIV care compared with those reporting
      low or no stigma at enrollment. Study findings highlight the continued importance
      of client-centered interventions and multi-sector collaborations to link PLWH to
      HIV medical care.

PMID- 29644492
TI  - Update on the Therapeutic Management of Hepatic Encephalopathy.
AB  - PURPOSE OF REVIEW: Hepatic encephalopathy (HE) is a common and devastating
      complication to chronic liver disease. In this paper, we summarize the latest
      research and evidence of both conventional and up-coming treatments. RECENT
      FINDINGS: Meta-analyses report beneficial effects of lactulose, branched-chain
      amino acids, rifaximin, and to some degree L-ornithine L-aspartate on the
      manifestations of HE in patients with cirrhosis, and generally the numbers needed
      to treat are low. Recent studies on newer HE treatments including ornithine
      phenylacetate, spherical carbon, and fecal microbiota transplant also report
      potentially beneficial effects on HE manifestations. The conventional treatments
      benefit patients with HE. Newer treatments are under study and more research is
      needed for their validation.

PMID- 29644494
TI  - Review of CRISPR/Cas9 sgRNA Design Tools.
AB  - The adaptive immunity system in bacteria and archaea, Clustered Regularly
      Interspaced Short Palindromic Repeats, CRISPR-associate (CRISPR/Cas), has been
      adapted as a powerful gene editing tool and got a broad application in genome
      research field due to its ease of use and cost-effectiveness. The performance of
      CRISPR/Cas relies on well-designed single-guide RNA (sgRNA), so a lot of
      bioinformatic tools have been developed to assist the design of highly active and
      specific sgRNA. These tools vary in design specifications, parameters, genomes
      and so on. To help researchers to choose their proper tools, we reviewed various
      sgRNA design tools, mainly focusing on their on-target efficiency prediction
      model and off-target detection algorithm.

PMID- 29644495
TI  - Does the Mouse Mammary Gland Arise from Unipotent or Multipotent Mammary
      Stem/Progenitor Cells?
AB  - The presence of long-lived lineage restricted progenitor and multipotent
      progenitor cells in adult mouse mammary gland for cancer development is
      compelling. Mammary cancers are phenotypically diverse This might be explained by
      transformation of long-lived, lineage-limited progenitor subpopulations. Mammary
      multipotent epithelial stem cells and their environmental niches must be
      considered, since their niche(s), once empty might be occupied by lineage-limited
      progenitors that are proximal. The existence of premalignant mammary populationst
      that manifest characteristics of lineage limitation argues strongly for this
      proposition.

PMID- 29644497
TI  - BECTS and CAE: a possible neurobiological continuum.

PMID- 29644496
TI  - Inter-subject FDG PET Brain Networks Exhibit Multi-scale Community Structure with
      Different Normalization Techniques.
AB  - Inter-subject networks are used to model correlations between brain regions and
      are particularly useful for metabolic imaging techniques, like 18F-2-deoxy-2
      (18F)fluoro-D-glucose (FDG) positron emission tomography (PET). Since FDG PET
      typically produces a single image, correlations cannot be calculated over time.
      Little focus has been placed on the basic properties of inter-subject networks
      and if they are affected by group size and image normalization. FDG PET images
      were acquired from rats (n = 18), normalized by whole brain, visual cortex, or
      cerebellar FDG uptake, and used to construct correlation matrices. Group size
      effects on network stability were investigated by systematically adding rats and
      evaluating local network connectivity (node strength and clustering coefficient).
      Modularity and community structure were also evaluated in the differently
      normalized networks to assess meso-scale network relationships. Local network
      properties are stable regardless of normalization region for groups of at least
      10. Whole brain-normalized networks are more modular than visual cortex- or
      cerebellum-normalized network (p < 0.00001); however, community structure is
      similar at network resolutions where modularity differs most between brain and
      randomized networks. Hierarchical analysis reveals consistent modules at
      different scales and clustering of spatially-proximate brain regions. Findings
      suggest inter-subject FDG PET networks are stable for reasonable group sizes and
      exhibit multi-scale modularity.

PMID- 29644498
TI  - The status quo and challenges of genetic diagnosis in children with steroid
      resistant nephrotic syndrome.

PMID- 29644499
TI  - Evaluation of prognostic models developed using standardised image features from
      different PET automated segmentation methods.
AB  - BACKGROUND: Prognosis in oesophageal cancer (OC) is poor. The 5-year overall
      survival (OS) rate is approximately 15%. Personalised medicine is hoped to
      increase the 5- and 10-year OS rates. Quantitative analysis of PET is gaining
      substantial interest in prognostic research but requires the accurate definition
      of the metabolic tumour volume. This study compares prognostic models developed
      in the same patient cohort using individual PET segmentation algorithms and
      assesses the impact on patient risk stratification. Consecutive patients (n =
      427) with biopsy-proven OC were included in final analysis. All patients were
      staged with PET/CT between September 2010 and July 2016. Nine automatic PET
      segmentation methods were studied. All tumour contours were subjectively analysed
      for accuracy, and segmentation methods with < 90% accuracy were excluded.
      Standardised image features were calculated, and a series of prognostic models
      were developed using identical clinical data. The proportion of patients changing
      risk classification group were calculated. RESULTS: Out of nine PET segmentation
      methods studied, clustering means (KM2), general clustering means (GCM3),
      adaptive thresholding (AT) and watershed thresholding (WT) methods were included
      for analysis. Known clinical prognostic factors (age, treatment and staging) were
      significant in all of the developed prognostic models. AT and KM2 segmentation
      methods developed identical prognostic models. Patient risk stratification was
      dependent on the segmentation method used to develop the prognostic model with up
      to 73 patients (17.1%) changing risk stratification group. CONCLUSION: Prognostic
      models incorporating quantitative image features are dependent on the method used
      to delineate the primary tumour. This has a subsequent effect on risk
      stratification, with patients changing groups depending on the image segmentation
      method used.

PMID- 29644500
TI  - Administration of Probiotics Improves the Brine Shrimp Production and Prevents
      Detrimental Effects of Pathogenic Vibrio Species.
AB  - In this study, we evaluated a consortium of probiotic bacteria as an
      environmentally-friendly strategy for controlling pathogenic Vibrio species
      during the brine shrimp incubation period. Probiotic strains were initially
      selected on basis of (i) their ability to colonize the cyst surfaces, (ii) their
      absence of cross-inhibitory effects, and (iii) no detrimental effect on cyst
      hatching. The cysts and nauplius surfaces were immediately colonized after the
      application of selected probiotic strains, without detrimental effects on
      survival. Ten probiotic strains were mixed at similar proportions (probiotic
      consortium) and evaluated at different concentrations into brine shrimp cultures
      during incubation and early stages of development. Subsequently, these cultures
      were challenged with Vibrio parahaemolyticus and Vibrio harveyi. The probiotic
      consortium was effective to reduce the abundance of pathogenic Vibrio species and
      to prevent the mortality during Vibrio challenges; however, its effect was
      concentration-dependent and was successful at a starting concentration of 1.8 *
      106 CFU/ml. Our results suggest that this probiotic consortium offers an
      alternative to antimicrobial agents routinely used to reduce the incidence and
      prevalence of pathogenic Vibrio species in brine shrimp production.

PMID- 29644501
TI  - Ethnic disparities in estimated cardiovascular disease risk in Amsterdam, the
      Netherlands : The HELIUS study.
AB  - BACKGROUND: Ethnic differences have been reported in cardiovascular disease (CVD)
      risk factors. It is still unclear which ethnic groups are most at risk for CVD
      when all traditional CVD risk factors are considered together as overall risk.
      OBJECTIVES: To examine ethnic differences in overall estimated CVD risk and the
      risk factors that contribute to these differences. DESIGN: Using data of the
      multi-ethnic HELIUS study (HEalthy LIfe in an Urban Setting) from Amsterdam, we
      examined whether estimated CVD risk and risk factors among those eligible for CVD
      risk estimation differed between participants of Dutch, South Asian Surinamese,
      African Surinamese, Ghanaian, Turkish and Moroccan origin. Using the Systematic
      COronary Risk Evaluation (SCORE) algorithm, we estimated risk of fatal CVD and
      risk of fatal plus non-fatal CVD. These risks were compared between ethnic groups
      via age-adjusted linear regression analyses. RESULTS: The SCORE algorithm was
      applicable to 9,128 participants. Relative to the fatal CVD risk of participants
      of Dutch origin, South Asian Surinamese participants showed a higher fatal CVD
      risk, Ghanaian males a lower fatal CVD risk, and participants of other ethnic
      origins a similar fatal CVD risk. For fatal plus non-fatal CVD risk, African
      Surinamese and Turkish men also showed a higher risk. When diabetes was
      incorporated in the CVD risk algorithm, all but Ghanaian men showed a higher CVD
      risk relative to the participants of Dutch origin (betas ranging from 0.98
      3.10%). The CVD risk factors that contribute the most to these ethnic differences
      varied between ethnic groups. CONCLUSION: Ethnic minority groups are at a greater
      estimated risk of fatal plus non-fatal CVD relative to the group of native Dutch.
      Further research is necessary to determine whether this will translate to ethnic
      differences in CVD incidence and, if so, whether ethnic-specific CVD prevention
      strategies are warranted.

PMID- 29644502
TI  - Healing in the colourful HELIUS experience.

PMID- 29644503
TI  - Inequalities in child immunization coverage in Ghana: evidence from a
      decomposition analysis.
AB  - Childhood vaccination has been promoted as a global intervention aimed at
      improving child survival and health, through the reduction of vaccine preventable
      deaths. However, there exist significant inequalities in achieving universal
      coverage of child vaccination among and within countries. In this paper, we
      examine rural-urban inequalities in child immunizations in Ghana. Using data from
      the recent two waves of the Ghana Demographic and Health Survey, we examine the
      probability that a child between 12 and 59 months receives the required
      vaccinations and proceed to decompose the sources of inequalities in the
      probability of full immunization between rural and urban areas. We find
      significant child-specific, maternal and household characteristics on a child's
      immunization status. The results show that children in rural areas are more
      likely to complete the required vaccinations. The direction and sources of
      inequalities in child immunizations have changed between the two survey waves. We
      find a pro-urban advantage in 2008 arising from differences in observed
      characteristics whilst a pro-rural advantage emerges in 2014 dominated by the
      differences in coefficients. Health system development and campaign efforts have
      focused on rural areas. There is a need to also specifically target vulnerable
      children in urban areas, to maintain focus on women empowerment and pay attention
      to children from high socio-economic households in less favourable economic
      times.

PMID- 29644504
TI  - Impact of smoking history on the outcomes of women with early-stage breast
      cancer: a secondary analysis of a randomized study.
AB  - To assess the impact of smoking history on the outcomes of early-stage breast
      cancer patients treated with sequential anthracyclines-taxanes in a randomized
      study. This is a secondary analysis of patient-level data of 1242 breast cancer
      patients referred for adjuvant chemotherapy in the BCIRG005 clinical trial.
      Overall survival was assessed according to smoking history through Kaplan-Meier
      analysis. Univariate and multivariate Cox regression analyses of factors
      affecting overall and relapse-free survival were subsequently conducted. Factors
      that were evaluated included: age, performance status, number of chemotherapy
      cycles, T stage, lymph node ratio, estrogen receptor status, adjuvant
      radiotherapy and smoking history. Kaplan-Meier analysis of overall survival
      according to smoking status (ever smoker vs. never smoker) was conducted. There
      was a trend toward a better overall survival among never smokers compared to ever
      smokers; however, it was not statistically significant (P = 0.098). The following
      factors were associated with better overall survival in multivariate analysis:
      older age (P = 0.011), complete chemotherapy course (P = 0.002), lower T stage (P
      < 0.0001), lower lymph node ratio (P < 0.0001) and positive estrogen receptor
      status (P = 0.006). Otherwise, the following factors were associated with better
      relapse-free survival in multivariate analysis: older age (P = 0.001), never
      smoking status (P = 0.021), lower T stage (P = 0.028), lower lymph node ratio (P
      < 0.0001) and positive estrogen receptor status (P < 0.0001). Early-stage breast
      cancer patients with a positive smoking history experienced worse relapse-free
      survival compared to never smokers. Physicians managing breast cancer patients
      should prioritize discussion about the benefits of smoking cessation when
      counseling their patients.

PMID- 29644505
TI  - Cardiotoxicity of Immunotherapy: Incidence, Diagnosis, and Management.
AB  - PURPOSE OF REVIEW: This review describes cardiotoxicity associated with adoptive
      T cell therapy and immune checkpoint blockade. RECENT FINDINGS: Cardiotoxicity is
      a rare but potentially fatal complication associated with novel immunotherapies.
      Both affinity-enhanced and chimeric antigen receptor T cells have been reported
      to cause hypotension, arrhythmia, and left ventricular dysfunction, typically in
      the setting of cytokine release syndrome. Immune checkpoint inhibitors are
      generally well-tolerated but have the potential to cause myocarditis, with
      clinical presentations ranging from asymptomatic cardiac biomarker elevation to
      heart failure, arrhythmia, and cardiogenic shock. Electrocardiography, cardiac
      biomarker measurement, and cardiac imaging are key components of the diagnostic
      evaluation. For suspected myocarditis, endomyocardial biopsy is recommended if
      the diagnosis remains unclear after initial testing. The incidence of
      immunotherapy-associated cardiotoxicity is likely underestimated and may increase
      as adoptive T cell therapy and immune checkpoint inhibitors are used in larger
      populations and for longer durations of therapy. Baseline and serial cardiac
      evaluation is recommended to facilitate early identification and treatment of
      cardiotoxicity.

PMID- 29644506
TI  - Uptake and accumulation of potentially toxic elements in colonized plant species
      around the world's largest antimony mine area, China.
AB  - To provide information on reclamation of multi-heavy metal polluted soils with
      conception of phytostabilization, a field survey on the uptake and accumulation
      of potentially toxic elements such as antimony (Sb), arsenic (As), lead (Pb),
      cadmium (Cd), copper (Cu), and zinc (Zn) in colonized plant species around the
      world's largest antimony mine area, China, was conducted. Samples including
      leaves and shoots (including roots and stems) of colonized plants as well as
      rhizospheric soils were collected from eight sampling zones in the studied area.
      The results showed that the contents of Cu, Zn, and Pb in rhizospheric soils
      below plants were comparable to the corresponding background values of Hunan
      province, otherwise Sb, Cd, and As contents were extremely high (17-106, 17-87,
      and 3-7 times of the corresponding background values). The highest concentration
      of Sb was found in Aster subulatus (410 mg kg-1); Cd, As, and Zn were in Herba
      bidentis bipinnatae (10.9, 264, and 265 mg kg-1, respectively); and Cu was in
      Artemisia lavandulaefolia (27.1 mg kg-1). It also exhibited that all the contents
      of As in leaves were several times of those in shoots of plants, Cd and other
      heavy metals showed in a similar pattern in several studied species, implying
      that the uptake route of these heavy metals via foliar might contribute to the
      accumulation. With high bioconcentration factors of heavy metals (more than 1,
      except for Zn), together with the growth abundance, Herba bidentis bipinnatae was
      considered as the most suitable colonized species for phytostabilization of the
      multi-heavy metal pollution in soils on this antimony mine area.

PMID- 29644507
TI  - The Impact of Obesity on Breast Cancer.
AB  - The rates of obesity are increasing worldwide and this condition is now
      recognized as a leading preventable cause of cancer. Several diseases are
      directly related to obesity, including diabetes, hypertension, atherosclerosis,
      stroke, musculoskeletal disorders, and a diverse range of malignances-such as
      breast cancer. Obesity is associated with an increased risk of postmenopausal
      estrogen receptor-positive breast cancer and worse cancer-related outcomes for
      all breast tumor subtypes. Several mechanisms have been proposed to contribute to
      the obesity-cancer link, including high levels of circulating and local
      estrogens, altered amounts of adipokines (leptin and adiponectin), disrupted
      insulin/IGF signaling, modifications within the microbiome, and local and
      systemic effects of inflammation. Here we will review recent advances in our
      understanding of the complex signaling pathways underlying the obesity-cancer
      link. An improved understanding of these processes is anticipated to propel novel
      and effective intervention strategies to reduce the global obesity-cancer burden.

PMID- 29644508
TI  - The first complete mitochondrial genome of a parasitic isopod supports Epicaridea
      Latreille, 1825 as a suborder and reveals the less conservative genome of
      isopods.
AB  - The complete mitochondrial genome sequence of the holoparasitic isopod Gyge
      ovalis (Shiino, 1939) has been determined. The mitogenome is 14,268 bp in length
      and contains 34 genes: 13 protein-coding genes, two ribosomal RNA, 19 tRNA and a
      control region. Three tRNA genes (trnE, trnI and trnS1) are missing. Most of the
      tRNA genes show secondary structures which derive from the usual cloverleaf
      pattern except for trnC which is characterised by the loss of the DHU-arm.
      Compared to the isopod ground pattern and Eurydice pulchra Leach, 1815 (suborder
      Cymothoida Wagele, 1989), the genome of G. ovalis shows few differences, with
      changes only around the control region. However, the genome of G. ovalis is very
      different from that of non-cymothoidan isopods and reveals that the gene order
      evolution in isopods is less conservative compared to other crustaceans.
      Phylogenic trees were constructed using maxiumum likelihood and Bayesian
      inference analyses based on 13 protein-coding genes. The results do not support
      the placement of G. ovalis with E. pulchra and Bathynomus sp. in the same
      suborder; rather, G. ovalis appears to have a closer relationship to Ligia
      oceanica (Linnaeus, 1767), but this result suggests a need for more data and
      further analysis. Nevertheless, these results cast doubt that Epicaridea
      Latreille, 1825 can be placed as an infraorder within the suborder Cymothoida,
      and Epicaridea appears to also deserve subordinal rank. Further development of
      robust phylogenetic relationships across Isopoda Latreille, 1817 will require
      more genetic data from a greater diversity of taxa belonging to all isopod
      suborders.

PMID- 29644509
TI  - Applications of Colon Capsule Endoscopy.
AB  - PURPOSE OF REVIEW: This is a review of colon capsule endoscopy (CCE) with a focus
      on its recent developments, technological improvements, and current and potential
      future indications. RECENT FINDINGS: Based on the current literature, CCE II
      demonstrates comparable polyp detection rates as optical colonoscopy and CT
      colonography, and improved cost-effectiveness. The main limitation to patient
      acceptance is the requirement of a rigorous bowel preparation. Preliminary
      studies show good correlation between CCE and optical colonoscopy for assessment
      of colonic disease activity in inflammatory bowel disease (IBD). CCE II is
      currently FDA, approved as an adjunctive test in patients with prior incomplete
      colonoscopy, and in the evaluation of patients with suspected lower
      gastrointestinal bleeding. The test is approved in Europe as one of the options
      for average-risk colorectal cancer screening, and high-risk screening in patients
      with contraindications or unwilling to undergo colonoscopy. CCE has a potential
      role in the evaluation and monitoring of colonic disease activity in IBD. Future
      technological advances should focus on minimizing bowel preparation, improvement
      in reading times, and development of therapeutic capabilities. * With
      technological improvements, the second-generation colon capsule has a
      significantly higher sensitivity than the first-generation capsule for detection
      of colon polyps. * Colon capsule endoscopy has been approved in Europe as an
      option for average-risk colorectal cancer screening, and high-risk screening in
      patients with contraindications or unwilling to undergo colonoscopy. * Colon
      capsule endoscopy has received FDA approval as an option for colorectal cancer
      screening in patients with prior incomplete colonoscopy, and in evaluation of
      patients with suspected lower gastrointestinal bleeding. * Colon capsule
      endoscopy may have a role in evaluation and monitoring of inflammatory bowel
      disease. * Colon capsule endoscopy currently requires a bowel preparation that is
      more rigorous than colonoscopy.

PMID- 29644510
TI  - A Raman-spectroscopy-based approach for detection and discrimination of
      Streptococcus thermophilus and Lactobacillus bulgaricus phages at low titer in
      raw milk.
AB  - In this study, a method combining Raman spectroscopy with chemometric analysis
      was developed for detection of phage presence in raw milk and discrimination of
      Streptococcus thermophilus and Lactobacillus bulgaricus phages which are among
      the main phages causing problems in dairy industry. For this purpose, S.
      thermophilus and L. bulgaricus phages were added into raw milk separately, and
      then some pretreatments such as fat separation, removal of casein, and filtration
      were applied to the raw milk samples. Raman spectra of the samples were collected
      and then analyzed using principal component analysis in order to discriminate
      these phages in raw milk. In the next step, dilutions of S. thermophilus phages
      in pretreated raw milk were prepared, and Raman spectra were collected. These
      spectra were analyzed by using partial least squares method to quantify phages in
      low titer. Consequently, it has been demonstrated that S. thermophilus and L.
      bulgaricus phages, which have titers sufficient to fail the fermentation (~ 107
      pfu/mL) and have lower titers (102-103 pfu/mL), could be discriminated from
      antibiotic and each other. Additionally, low concentrations of S. thermophilus
      phages (102 pfu/mL) could be detected through Raman spectroscopy with a short
      analysis time (60 min) and high coefficient of determination (R2) values for both
      calibration (0.985) and validation (0.906) with a root mean square error of
      calibration of 70.54 and root mean square error of prediction of 165.47. However,
      a lower success was achieved with L. bulgaricus phages and the obtained
      coefficient of determination values were not sufficiently high (0.649).

PMID- 29644511
TI  - Virulence-associated genes and antibiotic susceptibility among vaginal and rectal
      Escherichia coli isolates from healthy pregnant women in Poland.
AB  - Vaginal and/or rectal Escherichia coli colonization of pregnant women is
      sometimes associated with neonatal infections. Despite the relevance of these
      strains, they have been rarely described before. Thus, the aim of this study was
      to compare vaginal (VEC) and rectal E. coli (REC) isolates in respect of
      antimicrobial susceptibility and the frequency of virulence-associated genes
      (VAGs). The antimicrobial susceptibility of 50 VEC and 50 REC isolates was
      performed by using the disc diffusion method, and VAGs were detected by PCR.
      There were no significant differences in the antimicrobial resistance between VEC
      and REC. Both VEC and REC isolates were mostly resistant to ticarcillin (36 and
      30%) and ampicillin (36 and 22%). None of the tested isolates was positive for
      ESBL. Gene's fimH, fimA, sfa/foc, iutA, ibeA, hlyF, and neuC were detected,
      respectively, in 98, 92, 32, 28, 12, 8, and 2% of VEC and in 94, 72, 12, 34, 8,
      10, and 8% of REC isolates. The co-occurrence of fimA/H and sfa/foc genes was
      significantly more prevalent among VEC isolates, in comparison to REC isolates.
      The study indicated that VEC and REC isolates are quite similar in terms of
      antimicrobial non-susceptibility and VAGs.

PMID- 29644512
TI  - Cognitive-behavioral therapy improves the quality of life of patients with
      acromegaly.
AB  - BACKGROUND: The delayed diagnosis, altered body image, and clinical complications
      associated with acromegaly impair quality of life. PURPOSE: To assess the
      efficacy of the cognitive-behavioral therapy (CBT) technique "Think Healthy" to
      increase the quality of life of patients with acromegaly. METHODS: This non
      randomized clinical trial examined ten patients with acromegaly (nine women and
      one man; mean age, 55.5 +/- 8.4 years) from a convenience sample who received
      CBT. The intervention included nine weekly group therapy sessions. The quality of
      life questionnaire the 36-Item Short Form Survey (SF-36) and the Beck Depression
      Inventory (BDI) were administered during the pre- and post-intervention phases.
      The Wilcoxon signed-rank test was performed to assess the occurrence of
      significant differences. RESULTS: According to the SF-36, the general health
      domain significantly improved (d'  = - 0.264; p = 0.031). The mental health
      domain improved considerably (d'  = - 1.123; p = 0.012). Physical functioning
      showed a non-significant trend toward improvement (d'  = - 0.802; p = 0.078),
      although four of the five patients who showed floor effects improved and remained
      at this level. Regarding emotional well-being, five patients showed floor effects
      and four improved, and the condition did not change among any of the four
      patients who showed ceiling effects. No significant changes were found with
      regard to the other domains. No significant differences in the BDI were found
      before or after the intervention. CONCLUSION: The technique presented herein
      effectively improved the quality of life of patients with acromegaly with
      different levels of disease activity, type, and treatment time.

PMID- 29644513
TI  - Folding a viral peptide in different membrane environments: pathway and sampling
      analyses.
AB  - Flock House virus (FHV) is a well-characterized model system to study infection
      mechanisms in non-enveloped viruses. A key stage of the infection cycle is the
      disruption of the endosomal membrane by a component of the FHV capsid, the
      membrane active gamma peptide. In this study, we perform all-atom molecular
      dynamics simulations of the 21 N-terminal residues of the gamma peptide
      interacting with membranes of differing compositions. We carry out umbrella
      sampling calculations to study the folding of the peptide to a helical state in
      homogenous and heterogeneous membranes consisting of neutral and anionic lipids.
      From the trajectory data, we evaluate folding energetics and dissect the
      mechanism of folding in the different membrane environments. We conclude the
      study by analyzing the extent of configurational sampling by performing time
      lagged independent component analysis.

PMID- 29644514
TI  - Chemical structures of oligosaccharides in milk of the raccoon (Procyon lotor).
AB  - In this study on milk saccharides of the raccoon (Procyonidae: Carnivora), free
      lactose was found to be a minor constituent among a variety of neutral and acidic
      oligosaccharides, which predominated over lactose. The milk oligosaccharides were
      isolated from the carbohydrate fractions of each of four samples of raccoon milk
      and their chemical structures determined by 1H-NMR and MALDI-TOF mass
      spectroscopies. The structures of the four neutral milk oligosaccharides were
      Fuc(alpha1-2)Gal(beta1-4)Glc (2'-fucosyllactose), Fuc(alpha1-2)Gal(beta1
      4)GlcNAc(beta1-3)Gal(beta1-4)Glc (lacto-N-fucopentaose IV), Fuc(alpha1
      2)Gal(beta1-4)GlcNAc(beta1-3)Gal(beta1-4)GlcNAc(beta1-3)Gal(beta1-4)Glc (fucosyl
      para lacto-N-neohexaose) and Fuc(alpha1-2)Gal(beta1-4)GlcNAc(beta1-3)[Fuc(alpha1
      2)Gal(beta1-4)GlcNAc(beta1-6)]Gal(beta1-4)Glc (difucosyl lacto-N-neohexaose). No
      type I oligosaccharides, which contain Gal(beta1-3)GlcNAc units, were detected,
      but type 2 saccharides, which contain Gal(beta1-4)GlcNAc units were present. The
      monosaccharide compositions of two of the acidic oligosaccharides were
      [Neu5Ac]1[Hex]6[HexNAc]4[deoxy Hex]2, while those of another two were
      [Neu5Ac]1[Hex]8[HexNAc]6[deoxy Hex]3. These acidic oligosaccharides contained
      alpha(2-3) or alpha(2-6) linked Neu5Ac, non reducing alpha(1-2) linked Fuc, poly
      N-acetyllactosamine (Gal(beta1-4)GlcNAc) and reducing lactose.

PMID- 29644515
TI  - Predictive ability of perioperative atrial fibrillation risk indices in cardiac
      surgery patients: a retrospective cohort study.
AB  - PURPOSE: The Multicenter Study of Perioperative Ischemia (McSPI) AFRisk index
      predicts postoperative atrial fibrillation (POAF) after cardiac surgery, but
      requires pre-, intra-, and postoperative data. Other more abbreviated risk
      indices exist, but there is no consensus on which risk index is optimal. We
      compared the discriminatory capacity of the McSPI AFRisk index with three indices
      containing only preoperative data (the CHA2DS2Vasc score, POAF score, and Kolek
      clinical risk prediction model), hypothesizing that the McSPI AFRisk index would
      have superior predictive capacity. METHODS: We retrospectively evaluated 783
      patients undergoing cardiac surgery using cardiopulmonary bypass. The predictive
      capacity of each index was assessed by comparing receiver-operating
      characteristic (ROC) curves, scaled Brier scores, net reclassification indices,
      and the integrated discrimination indices. RESULTS: The incidence of POAF was
      32.6%. The area under the curve (AUC) of the ROC curve were 0.77, 0.58, 0.66, and
      0.66 for the McSPI AFRisk index, CHA2DS2Vasc score, POAF score, and Kolek
      clinical risk prediction model, respectively. The McSPI AFRIsk index had the
      highest AUC (P < 0.0001). The scaled Brier scores for the McSPI AFRisk index,
      CHA2DS2Vasc score, POAF score, and Kolek clinical risk prediction model were
      0.23, 0.02, 0.08, and 0.07, respectively. Both net reclassification indices and
      integrated discrimination indices showed that the McSPI AFRisk index more
      appropriately identified patients at high risk of POAF. CONCLUSIONS: The McSPI
      AFRisk index showed superior ability to predict POAF after cardiac surgery
      compared with three other indices. When clinicians and investigators wish to
      measure the risk of POAF after cardiac surgery, they should consider using the
      McSPI AFRisk index.

PMID- 29644516
TI  - Correction to: Hypervigilance to a Gluten-Free Diet and Decreased Quality of Life
      in Teenagers and Adults with Celiac Disease.
AB  - The original version of the article unfortunately contained formatting errors in
      Table 3. The correct version of Table 3 is given in the Correction article.

PMID- 29644518
TI  - Mathematical Modelling of the Interaction Between Cancer Cells and an Oncolytic
      Virus: Insights into the Effects of Treatment Protocols.
AB  - Oncolytic virotherapy is an experimental cancer treatment that uses genetically
      engineered viruses to target and kill cancer cells. One major limitation of this
      treatment is that virus particles are rapidly cleared by the immune system,
      preventing them from arriving at the tumour site. To improve virus survival and
      infectivity Kim et al. (Biomaterials 32(9):2314-2326, 2011) modified virus
      particles with the polymer polyethylene glycol (PEG) and the monoclonal antibody
      herceptin. Whilst PEG modification appeared to improve plasma retention and
      initial infectivity, it also increased the virus particle arrival time. We derive
      a mathematical model that describes the interaction between tumour cells and an
      oncolytic virus. We tune our model to represent the experimental data by Kim et
      al. (2011) and obtain optimised parameters. Our model provides a platform from
      which predictions may be made about the response of cancer growth to other
      treatment protocols beyond those in the experiments. Through model simulations,
      we find that the treatment protocol affects the outcome dramatically. We quantify
      the effects of dosage strategy as a function of tumour cell replication and
      tumour carrying capacity on the outcome of oncolytic virotherapy as a treatment.
      The relative significance of the modification of the virus and the crucial role
      it plays in optimising treatment efficacy are explored.

PMID- 29644519
TI  - Stochastic Dynamics of Eukaryotic Flagellar Growth.
AB  - We study the dynamics of flagellar growth in eukaryotes where intraflagellar
      transporters (IFT) play a crucial role. First we investigate a stochastic version
      of the original balance point model where a constant number of IFT particles move
      up and down the flagellum. The detailed model is a discrete event vector-valued
      Markov process occurring in continuous time. First the detailed stochastic model
      is compared and contrasted with a simple scalar ordinary differential equation
      (ODE) model of flagellar growth. Numerical simulations reveal that the steady
      state mean value of the stochastic model is well approximated by the ODE model.
      Then we derive a scalar stochastic differential equation (SDE) as a first
      approximation and obtain a "small noise" approximation showing flagellar length
      to be Gaussian with mean and variance governed by simple ODEs. The accuracy of
      the small noise model is compared favorably with the numerical simulation results
      of the detailed model. Secondly, we derive a revised SDE for flagellar length
      following the revised balance point model proposed in 2009 in which IFT particles
      move in trains instead of in isolation. Small noise approximation of the revised
      SDE yields the same approximate Gaussian distribution for the flagellar length as
      the SDE corresponding to the original balance point model.

PMID- 29644517
TI  - Systemic Inflammatory Responses in Ulcerative Colitis Patients and Clostridium
      difficile Infection.
AB  - BACKGROUND/AIMS: Finding differences in systemic inflammatory response in
      ulcerative colitis (UC), UC with Clostridium difficile infection (CDI), and CDI
      could lead to a better ability to differentiate between UC with symptomatic CDI
      and UC with C. difficile colonization, and could identify specific inflammatory
      pathways for UC or CDI, which could be therapeutic targets. METHODS: We
      prospectively collected sera from symptomatic UC patients whose stools were
      tested for toxigenic C. difficile, and from CDI patients who did not have UC (CDI
      noUC). The UC patients with positive tests (UC-CDI) were further categorized into
      responders to CDI treatment (UC-CDI-R) and non-responders (UC-CDI-NR). We
      compared serum inflammatory mediators among groups using unadjusted and adjusted
      multivariable statistics. RESULTS: We included 117 UC [27 UC-CDI, 90 UC without
      CDI (UC-noCDI)] and 16 CDI-noUC patients. Principal component analysis (PCA) did
      not reveal significant differences either between UC-CDI and UC-noCDI groups, or
      between UC-CDI-R and UC-CDI-NR groups. In contrast, the PCA showed significant
      separation between the UC and CDI-noUC groups (P = 0.002). In these two groups,
      hepatocyte growth factor (HGF) and chemokine (C-C motif) ligand 2 (CCL2) levels
      were significantly lower and IL-23 levels were higher in UC patients in
      multivariable analyses. The model to distinguish UC from CDI including IL-23,
      HGF, CCL2, age, gender, and HGB had an AuROC of 0.93. CONCLUSION: Inflammatory
      profiles could not distinguish UC-CDI from UC-noCDI, and UC-CDI-R from UC-CDI-NR.
      However, the UC and CDI-noUC groups were significantly different. Future work
      should examine whether therapeutic agents inhibiting IL-23 or stimulating HGF can
      treat UC.

PMID- 29644520
TI  - The Linear Noise Approximation for Spatially Dependent Biochemical Networks.
AB  - An algorithm for computing the linear noise approximation (LNA) of the reaction
      diffusion master equation (RDME) is developed and tested. The RDME is often used
      as a model for biochemical reaction networks. The LNA is derived for a general
      discretization of the spatial domain of the problem. If M is the number of
      chemical species in the network and N is the number of nodes in the
      discretization in space, then the computational work to determine approximations
      of the mean and the covariances of the probability distributions is proportional
      to [Formula: see text] in a straightforward implementation. In our LNA algorithm,
      the work is proportional to [Formula: see text]. Since N usually is larger than
      M, this is a significant reduction. The accuracy of the approximation in the
      algorithm is estimated analytically and evaluated in numerical experiments.

PMID- 29644521
TI  - Functional connectivity change between posterior cingulate cortex and ventral
      attention network relates to the impairment of orientation for time in
      Alzheimer's disease patients.
AB  - Alzheimer's disease (AD) patients exhibit various cognitive dysfunctions,
      including impairment of orientation for time (OT). The brain regions underlying
      OT impairment remain to be elucidated. A previous single-photon emission computed
      tomography study has indicated hypoperfusion of the posterior cingulate cortex
      (PCC) in relation to deterioration of OT. In this study, we investigated whole
      brain functional connectivity changes of PCC using resting-state functional
      magnetic resonance imaging. Voxel-based functional connectivity with PCC was
      analyzed in OT-poor or OT-good AD patients, classified according to the mean OT
      scores of the Mini-Mental State Examination subscale. The connectivities of
      dorsal frontal lobe, and lateral parietal and lateral temporal lobes with PCC in
      the right hemisphere were reduced in the OT-poor AD group compared with the OT
      good AD group. A subtraction connectivity map of OT score differences (OT-good
      minus OT-poor) revealed the right middle temporal gyrus near the temporo-parietal
      junction as a significantly connected region with PCC. These results suggest that
      the right posterior part of the middle temporal gyrus may play an important role
      in OT in conjunction with PCC, and that disconnection between PCC and the right
      ventral attention network may cause OT disturbance in AD patients.

PMID- 29644522
TI  - Bioinformatic analysis reveals the key pathways and genes in early-onset breast
      cancer.
AB  - Early-onset breast cancer is the most prevalent cancer in the female. To identify
      the differentially expressed genes and the key signaling pathways in early-onset
      breast cancer, we have carried out the bioinformatic analysis of an RNA array
      dataset in the GEO database, GSE109169, which was acquired from early-onset
      breast cancer patient. A total of 118 differentially expressed genes in early
      onset breast cancer were significantly changed compared with that in adjacent
      normal tissues. Most of these genes are classified into three categories:
      signaling molecule, enzyme modulator, and hydrolase. Gene ontology terms reveal
      that most of these genes are involved in cellular and metabolic processes,
      biological regulation, binding and catalytic activities, and receptor regulation.
      Protein-protein interaction network was constructed and has two highly enriched
      modules: one with up-regulated genes and the other with down-regulated genes. The
      singling pathways are mainly enriched in the cellular immune system, lipid
      metabolism and other types of metabolic pathways. Finally, we have plotted the
      Kaplan-Meier curves of two up-regulated and two down-regulated genes for the
      overall survival prediction in breast cancer. These results greatly expand the
      current view of early-onset breast cancer and shed light on the discovery of drug
      candidates and the improvement for the prognosis.

PMID- 29644523
TI  - Psoriasis and risk of incident chronic kidney disease and end-stage renal
      disease: a systematic review and meta-analysis.
AB  - OBJECTIVES: Patients with psoriasis may have a higher risk of developing chronic
      kidney (CKD) and end-stage renal disease (ESRD) compared with general population.
      This systematic review and meta-analysis aimed to comprehensively investigate
      this association by reviewing all available evidence. METHODS: A systematic
      review was performed using MEDLINE and EMBASE database from inception to January
      2018 to identify all cohort studies that compared the risk of incident CKD and/or
      ESRD in patients with psoriasis versus individuals without psoriasis. Pooled risk
      ratio and 95% confidence interval were calculated using random-effect, generic
      inverse variance method. RESULTS: A total of four retrospective cohort studies
      with 199,808 patients with psoriasis were included. The risk of incident CKD and
      ESRD was significantly increased among patients with psoriasis with the pooled
      risk ratio of 1.34 (95% CI, 1.14-1.57) and 1.29 (95% CI, 1.05-1.60),
      respectively. CONCLUSION: A significantly increased risk of incident CKD and ESRD
      among patients with psoriasis compared with individuals without psoriasis was
      demonstrated in this study.

PMID- 29644524
TI  - Discontinuation of antiviral prophylaxis increased the risk of hepatitis B virus
      reactivation in glomerulonephritis patients under immunotherapy: a real-life
      observation.
AB  - PURPOSE: Antiviral prophylaxis is proved to be effective in reducing the risk of
      hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg)
      positive patients under immunotherapy. But outcomes referring to discontinuation
      of antiviral prophylaxis in these patients are lacking. METHODS: We performed a
      retrospective study of 105 HBsAg-positive patients under immunotherapy for
      glomerulonephritis and evaluated the incidence and risk factors for HBV
      reactivation. RESULTS: Among 105 patients, 55.24% completed antiviral
      prophylaxis, while 20.00% discontinued and 24.76% rejected antiviral prophylaxis.
      HBV reactivation was significantly different among completion, discontinuation,
      and rejection of antiviral prophylaxis: 5.17% versus 38.10% versus 15.38% in the
      incidence of HBV reactivation (P = 0.001), 3.45% versus 23.81% versus 11.54% in
      HBV DNA >= 5 Log copies/ml (P = 0.023), and 0 versus 14.29% versus 3.85% in
      hepatitis B e antigen seroconversion from negative to positive (P = 0.014).
      Survival curve showed the median occurrence time of HBV reactivation in
      discontinuation group was 32 months (95% CI 24-39 months), earlier than 69 months
      (95% CI 65-72 months) of completion group and 43 months (95% CI 37-49 months) of
      rejection group (chi2 = 13.780, P = 0.001). Univariate and multivariate analysis
      identified two independent risk factors for HBV reactivation: baseline HBV DNA
      detectable (OR 5.009, 95% CI 1.717-16.335, P = 0.012) and discontinuation of
      antiviral prophylaxis (OR 5.213, 95% CI 1.688-18.105, P = 0.011). CONCLUSIONS:
      Discontinuation of antiviral prophylaxis increased the risk of HBV reactivation
      in HBsAg-positive patients under immunotherapy for glomerulonephritis.

PMID- 29644525
TI  - Determination of NF-kappaB and RANKL levels in peripheral blood osteoclast
      precursor cells in chronic kidney disease patients.
AB  - PURPOSE: Chronic kidney disease (CKD) is a progressive condition characterized by
      irreversible loss of functional nephron mass due to variety of causes; an
      inevitable complication of CKD is metabolic bone disease, and this pathology is
      called as renal osteodystrophy (ROD). In this study, we aimed to determine the
      levels of serum sRANKL and intracellular NF-kappaB levels in peripheral blood
      osteoclast precursor cells in patients with stage 3 CKD. MATERIALS AND METHODS:
      Forty-one male patients aged 35-60 with CKD identified as stage 3 according to
      GFR calculated on the basis of creatinine values and 27 healthy male subjects
      with age ranging from 40 to 60 as control group were included in this study.
      Levels of biochemical parameters, vitamin D3, parathyroid hormone, bone mineral
      density, sRANKL and NF-kappaB were determined by using photometric,
      electrochemiluminescence, HPLC, ELISA and flow cytometric methods in control and
      patient groups, respectively. RESULTS: When stage 3 CKD patients were compared
      with controls, patients with stage 3 CKD had statistically significantly higher
      iPTH levels, but they had statistically significantly lower vitamin D3 levels.
      However, the other biochemical parameters, bone mineral density, sRANKL and NF
      kappaB levels did not reveal any significance. CONCLUSION: In conclusion, vitamin
      D3 and iPTH levels seem to be important parameters for evaluating the early
      stages of ROD. The lack of statistically significant differences in the levels of
      sRANKL and NF-kappaB suggests that these parameters are not sufficient in the
      evaluation of bone metabolism in the early stages of renal failure.

PMID- 29644526
TI  - Upregulated expression of human cathelicidin LL-37 in hypercholesterolemia and
      its relationship with serum lipid levels.
AB  - Dyslipidemia in patients with hypercholesterolemia has been recently linked to
      increased human cathelicidin LL-37 (LL-37) serum concentration. We tested a
      hypothesis that upregulated expression of LL-37 gene in peripheral blood
      leucocytes is involved in dyslipidemia in patients with hypercholesteremia.
      Patients with hypercholesterolemia were used in the study. Expression of LL-37
      and human glyceraldehyde-3-phosphate dehydrogenase in peripheral blood leucocytes
      were quantified by real-time RT-PCR. Serum LL-37 concentration was estimated by
      enzyme-linked immunosorbent assay. Serum lipid levels were assessed by
      absorptiometry in all cases. Patients with hypercholesterolemia as compared to
      control ones were characterized by (a) an up-regulation of LL-37 gene expression
      in peripheral blood leucocytes with parallel increase of serum LL-37
      concentration and (b) an increase of serum total and low-density lipoprotein
      cholesterol concentrations. Patients with hypercholesterolemia after a treatment
      with atorvastatin calcium 20 mg daily as compared to that patients before the
      treatment: an down-regulation of LL-37 gene expression in peripheral blood
      leucocytes with parallel decrease of serum LL-37 concentration. We also found
      significant correlation between serum LL-37 and high-density lipoprotein
      cholesterol levels (r = 0.7290, P < 0.0001). The results suggest that
      hypercholesterolemia is associated with an increased LL-37 gene expression in
      peripheral blood leucocytes. The correlation between serum LL-37 and high-density
      lipoprotein cholesterol levels suggests that LL-37 may play a key role in
      regulation of cholesterol levels in hypercholesterolemia.

PMID- 29644527
TI  - Gemcabene, a first-in-class lipid-lowering agent in late-stage development, down
      regulates acute-phase C-reactive protein via C/EBP-delta-mediated transcriptional
      mechanism.
AB  - Inflammation plays a key role in setting the stage leading to atherosclerosis
      progression, and high-sensitivity C-reactive protein (CRP) has been recognized as
      a predictor of cardiovascular risk. As a monotherapy and in combination with
      statins, gemcabene markedly reduced CRP in humans. Present investigation was
      undertaken to understand the mechanism of CRP reduction. In human hepatoma cells,
      gemcabene inhibited IL-6 plus IL-1beta-induced CRP production in a concentration
      dependent manner, reaching 70% inhibition at 2 mM. In TNF-alpha-stimulated
      primary human coronary artery endothelial cells, both CRP and IL-6 productions
      were reduced by 70% at 2 mM gemcabene concentration. To investigate the mechanism
      of gemcabene-mediated reduction of CRP, transfection studies were performed with
      human CRP regulatory sequences in luciferase/beta-gal system that showed 25-fold
      increase in IL-6- and IL-6 plus IL-1beta-stimulated CRP transcription. Luciferase
      activity was reduced by 50% by gemcabene, suggesting transcriptional down
      regulation of CRP. Site-directed mutagenesis of human CRP promoter revealed that
      the overlapping downstream C/EBP and NF-kappaB binding sites are important for
      gemcabene-mediated CRP transcription. Gel shift assays identified the
      transcription factor that binds to the downstream CRP promoter as C/EBP-delta. In
      conclusion, gemcabene decreases CRP by C/EBP-delta and NF-kappaB-mediated
      transcriptional mechanism and suppresses IL-6 and IL-1beta-induced CRP
      production.

PMID- 29644528
TI  - A novel, semi-synthetic diterpenoid 16(R and S)-phenylamino-cleroda-3,13(14), Z
      dien-15,16 olide (PGEA-AN) inhibits the growth and cell survival of human
      neuroblastoma cell line SH-SY5Y by modulating P53 pathway.
AB  - Neuroblastoma being the most common extracranial pediatric solid tumor accounts
      for 15% of overall cancer-related childhood mortalities. Resistance to
      chemotherapeutic drugs is one of the limiting factors for positive prognosis for
      neuroblastoma. Therefore, there is always a need for developing new therapeutic
      moieties which can become a future prospect of neuroblastoma therapy. Terpenoids
      being the largest natural compounds have demonstrated many biological activities
      including anticancer activity. Keeping in mind the role of terpenoids in
      biological system, we aimed to identify novel semi-synthetic terpenoid derived
      from cleroda diterpene, 16-oxo-cleroda-3,13(14)E-diene-15-oic acid (1) as a
      potential anticancer moiety against neuroblastoma. We choose gamma-amino gamma
      lactone (PGEA-AN, 2) of 1 to study further because it exhibited the most potent
      cytotoxic activity in preliminary screening. In comparison to cisplatin, PGEA-AN
      significantly decreased the nuclear area factor which suggest the potential
      apoptosis as cause of cell death. PGEA-AN demonstrated a significant increase in
      the percent of late apoptosis and necrotic cell death at 48-h treatment with IC50
      dose. PGEA-AN significantly increased expression of P53 and BAX with no or little
      effect on BCL2 shifting BAX/BCL2 towards BAX promoting apoptosis. Increment in
      mitochondrial permeability supports P53 pathway involvement. Despite similarity
      in actions with cisplatin, PGEA-AN has found to have no effect on renal system.
      Based on these observations, we suggest that PGEA-AN modulates P53 system which
      further leads to the death of the neuroblastoma cells with no effect on renal
      system in vivo owing it to be a future prospect for development of anticancer
      moiety against neuroblastoma.

PMID- 29644529
TI  - Effects of increased accumulation of doxorubicin due to emodin on efflux
      transporter and LRP1 expression in lung adenocarcinoma and colorectal carcinoma
      cells.
AB  - Treatment with doxorubicin (dox) and emodin, separately and together, under
      normoxic and hypoxia-like conditions induced by CoCl2, led to greater
      intracellular compound accumulation over 10 h post-addition in the presence of
      CoCl2 in lung adenocarcinoma (A549) and colorectal carcinoma (HCT-15) cell lines.
      Confocal microscopy revealed that emodin, by itself, showed high cytosolic
      distribution in both cell lines, at 40 min post-addition but had entered the
      nuclei by 2 h, while dox entered the nuclei by 40 min. Both compounds modulated
      the expression of the efflux transporters (PgP, ABCG2, or MRP1-4) and the
      endocytic receptor, low-density lipoprotein receptor-related protein 1 (LRP1), to
      different extents under the study conditions. Efflux transporter upregulation was
      linked to lower intracellular compound levels due to greater efflux. Increased
      dox accumulation was accompanied by unaltered expression or upregulation of LRP1
      in A549 cells. In both cell lines, increased accumulation of dox and emodin was
      observed whenever LRP1 and the efflux transporters known to transport dox and
      emodin were all up- or downregulated concomitantly. Increased growth inhibition
      was linked to co-treatment with dox and emodin and with increased ligand
      accumulation. The results presented in this study raise the hypothesis that
      higher production of LRP1 protein may be associated with higher endocytosis of
      upregulated transporter proteins at the cell surface, and hence, increased dox
      and emodin accumulation and growth inhibition. If so, elevation of LRP1
      expression may be a useful target for interventions to promote the efficacy of
      these and other anticancer drugs.

PMID- 29644530
TI  - A posttraumatic pseudoaneurysm of the left radial artery as a result of a stab
      wound in an 8-year-old girl.
AB  - Pseudoaneurysms arise from a disruption of arterial wall continuity and are most
      commonly related to a penetrating trauma, an arterial wall inflammation or
      iatrogenic causes. They differ from real aneurysms due to a lack of one or more
      layers of the arterial wall. The frequency of peripheral artery pseudoaneurysms
      in the upper extremities is less than in the lower extremities and its most
      common cause is a gunshot or a stab wound. The risk of a rupture is higher than
      in true aneurysms due to a lack of wall layers, therefore requiring surgical
      treatment in most cases. Here we describe an unusual case of an 8-year-old girl
      who presented to the emergency department complaining of swelling and pain in her
      left distal forearm. One month before admission she experienced a penetrating
      trauma in the same area due to a self inflicted stab wound. After clinical and
      duplex ultrasonography evaluation the tumefaction proved to be a posttraumatic
      pseudoaneurysm of the left radial artery.

PMID- 29644531
TI  - Splanchnic Vein Thrombosis in the Myeloproliferative Neoplasms.
AB  - PURPOSE OF REVIEW: To review the epidemiology, diagnostic challenges,
      pathogenesis, and treatment strategies for patients with myeloproliferative
      neoplasm-associated splanchnic vein thrombosis. RECENT FINDINGS: The epidemiology
      of myeloproliferative neoplasm-associated splanchnic vein thrombosis (MPN-SVT)
      has been well characterized. While typical MPN-associated thrombosis affects
      older patients and involves the arterial circulation, MPN-SVT mostly impacts
      younger women. An association with JAK2 V617F is well-known; recent studies have
      demonstrated only a weak association with CALR mutations. JAK inhibition may
      represent a novel treatment strategy, complementing anticoagulation, and
      management of portal hypertension. While the epidemiology has been well
      characterized, more work is needed to identify novel contributors to disease
      pathogenesis, beyond the JAK2 V617F mutation itself, and endothelial compromise.
      Testing for MPN mutations in the setting of non-cirrhotic SVT is commonplace;
      JAK2 V617F is the most likely to be identified. Testing for CALR or MPL mutations
      requires clinical judgement, though not unreasonable. The mainstay of therapy is
      indefinite anticoagulation; the role of direct oral anticoagulants is unclear.
      JAK inhibition may play a role in addressing associated splenomegaly and portal
      hypertension.

PMID- 29644533
TI  - Systematic Review of Clinical Outcomes Following Various Treatment Options for
      Patients with Extraabdominal Desmoid Tumors.
AB  - BACKGROUND: Desmoid tumors (DT) are rare clonal proliferations that arise from
      mesenchymal cells. These tumors do not metastasize but are locally aggressive,
      and their growth may lead to significant morbidity. Their clinical course is both
      variable and unpredictable; tumors may rapidly progress but in other instances
      remain stable or regress without intervention. AIMS: To examine current treatment
      of DT and assist with decision-making at time of presentation. METHODS: A
      literature search was conducted of MEDLINE and Cochrane databases for published
      studies (1995-July 2015) using the search terms fibromatosis aggressive, desmoid
      with drug therapy, radiation therapy, prevention and control, radiotherapy,
      surgery, and therapy. Articles were categorized as surgery, radiation, surgery +
      radiation, systemic therapy, and front-line observation. Articles were included
      if they reported a retrospective or prospective comparative or observational
      study with an analyzed sample size of 10 patients or more with confirmed
      diagnosis of desmoid tumor and described one of the following clinical outcomes:
      relapse- or progression-free survival, local control rate, response rate.
      RESULTS: 258 articles were reviewed; following screening for eligibility, 54 were
      identified; following full-text screen, 31 were included in final evaluation. The
      control rate for patients treated with a "wait and see" observational approach
      compared favorably with management with surgery and resulted in disease control
      rates of between 60 and 92%. CONCLUSIONS: Decision-making in this rare tumor is
      complicated by the range of treatment options available. Our evidence supports
      use of an upfront observational approach.

PMID- 29644532
TI  - Methamphetamine Induces Apoptosis of Microglia via the Intrinsic Mitochondrial
      Dependent Pathway.
AB  - Methamphetamine (METH) is a drug of abuse, the acute and chronic use of which
      induces neurotoxic responses in the human brain, ultimately leading to
      neurocognitive disorders. Our goals were to understand the impact of METH on
      microglial mitochondrial respiration and to determine whether METH induces the
      activation of the mitochondrial-dependent intrinsic apoptosis pathway in
      microglia. We assessed the expression of pro- apoptosis genes using qPCR of RNA
      extracted from a human microglial cell line (HTHU). We examined the apoptosis
      inducing effects of METH on microglial cells using digital holographic microscopy
      (DHM) to quantify real-time apoptotic volume decrease (AVD) in microglia in a
      noninvasive manner. METH treatment significantly increased AVD, activated Caspase
      3/7, increased the gene expression levels of the pro- apoptosis proteins, APAF-1
      and BAX, and decreased mitochondrial DNA content. Using immunofluorescence
      analysis, we found that METH increased the expression of the mitochondrial
      proteins cytochrome c and MCL-1, supporting the activation of mitochondrion
      dependent (intrinsic) apoptosis pathway. Cellular bio-energetic flux analysis by
      Agilent Seahorse XF Analyzer revealed that METH treatment increased both
      oxidative and glycolytic respiration after 3 h, which was sustained for at least
      24 h. Several events, such as oxidative stress, neuro-inflammatory responses, and
      mitochondrial dysfunction, may converge to mediate METH-induced apoptosis of
      microglia that may contribute to neurotoxicity of the CNS. Our study has
      important implications for therapeutic strategies aimed at preserving
      mitochondrial function in METH abusing patients.

PMID- 29644534
TI  - Co-designing Urban Living Solutions to Improve Older People's Mobility and Well
      Being.
AB  - Mobility is a key aspect of active ageing enabling participation and autonomy
      into later life. Remaining active brings multiple physical but also social
      benefits leading to higher levels of well-being. With globally increasing levels
      of urbanisation alongside demographic shifts meaning in many parts of the world
      this urban population will be older people, the challenge is how cities should
      evolve to enable so-called active ageing. This paper reports on a co-design study
      with 117 participants investigating the interaction of existing urban spaces and
      infrastructure on mobility and well-being for older residents (aged 55 + years)
      in three cities. A mixed method approach was trialled to identify locations
      beneficial to subjective well-being and participant-led solutions to urban
      mobility challenges. Spatial analysis was used to identify key underlying factors
      in locations and infrastructure that promoted or compromised mobility and well
      being for participants. Co-designed solutions were assessed for acceptability or
      co-benefits amongst a wider cross-section of urban residents (n = 233) using
      online and face-to-face surveys in each conurbation. Our analysis identified
      three critical intersecting and interacting thematic problems for urban mobility
      amongst older people: The quality of physical infrastructure; issues around the
      delivery, governance and quality of urban systems and services; and the attitudes
      and behaviors of individuals that older people encounter. This identified
      complexity reinforces the need for policy responses that may not necessarily
      involve design or retrofit measures, but instead might challenge perceptions and
      behaviors of use and access to urban space. Our co-design results further
      highlight that solutions need to move beyond the generic and placeless, instead
      embedding specific locally relevant solutions in inherently geographical spaces,
      populations and processes to ensure they relate to the intricacies of place.

PMID- 29644535
TI  - A Secondary Spatial Analysis of Gun Violence near Boston Schools: a Public Health
      Approach.
AB  - School neighborhood violence continues to be a major public health problem among
      urban students. A large body of research addresses violence at school; however,
      fewer studies have explored concentrations of violence in areas proximal to
      schools. This study aimed to quantify the concentration of shootings near schools
      to elucidate the place-based dynamics that may be focal points for violence
      prevention. Geocoded databases of shooting and school locations were used to
      examine locational patterns of firearm shootings and elementary, middle, and high
      schools in Boston, Massachusetts. Analyses utilized spatial statistics for point
      pattern data including distance matrix and K function methodology to quantify the
      degree of spatial dependence of shootings around schools. Results suggested that
      between 2012 and 2015, there were 678 shooting incidents in Boston; the average
      density was 5.1 per square kilometer. The nearest neighbor index (NNI = 0.335 km,
      p < .001, O = 0.95 km, E = 0.28 km) and G function analysis revealed a clustered
      pattern of gun shooting incidents indicative of a spatially non-random process.
      The mean and median distance from any school to the nearest shooting location was
      0.35 and 0.33 km, respectively. A majority (56%, 74/133) of schools in Boston had
      at least one shooting incident within 400 m, a distance that would take about 5
      min to walk if traveling by foot. The bivariate K function indicated that a
      significantly greater number of shootings were clustered within short distances
      from schools than would be expected under a null hypothesis of no spatial
      dependence. Implications for students attending schools in racially homogenous
      neighborhoods across all income levels are discussed.

PMID- 29644536
TI  - Cigarette smoke and nicotine effects on brain proinflammatory responses and
      behavioral and motor function in HIV-1 transgenic rats.
AB  - Cognitive impairment in HIV-1 infection is associated with the induction of
      chronic proinflammatory responses in the brains of infected individuals. The risk
      of HIV-related cognitive impairment is increased by cigarette smoking, which
      induces brain inflammation in rodent models. To better understand the role of
      smoking and the associated immune response on behavioral and motor function in
      HIV infection, wild-type F344 and HIV-1 transgenic (HIV1Tg) rats were exposed to
      either smoke from nicotine-containing (regular) cigarettes, smoke from nicotine
      free cigarettes, or to nicotine alone. The animals were then tested using the
      rotarod test (RRT), the novel object recognition test (NORT), and the open field
      test (OFT). Subsequently, brain frontal cortex from the rats was analyzed for
      levels of TNF-alpha, IL-1, and IL-6. On the RRT, impairment was noted for F344
      rats exposed to either nicotine-free cigarette smoke or nicotine alone and for
      F344 and HIV1Tg rats exposed to regular cigarette smoke. Effects from the
      exposures on the OFT were seen only for HIV1Tg rats, for which function was worse
      following exposure to regular cigarette smoke as compared to exposure to nicotine
      alone. Expression levels for all three cytokines were overall higher for HIV1Tg
      than for F344 rats. For HIV1Tg rats, TNF-alpha, IL-1, and IL-6 gene expression
      levels for all exposure groups were higher than for control rats. All F344 rat
      exposure groups also showed significantly increased TNF-alpha expression levels.
      However, for F344 rats, IL-1 expression levels were higher only for rats exposed
      to nicotine-free and nicotine-containing CS, and no increase in IL-6 gene
      expression was noted with any of the exposures as compared to controls. These
      studies, therefore, demonstrate that F344 and HIV1Tg rats show differential
      behavioral and immune effects from these exposures. These effects may potentially
      reflect differences in the responsiveness of the various brain regions in the two
      animal species as well as the result of direct toxicity mediated by the
      proinflammatory cytokines that are produced by HIV proteins and by other factors
      that are present in regular cigarette smoke.

PMID- 29644537
TI  - Drug-Drug Interaction Profile of the Fixed-Dose Combination Tablet Regimen
      Ledipasvir/Sofosbuvir.
AB  - Ledipasvir/sofosbuvir (Harvoni(r)), a fixed-dose combination tablet of an NS5A
      inhibitor ledipasvir and an NS5B polymerase inhibitor sofosbuvir, is approved for
      the treatment of chronic hepatitis C virus infection. Ledipasvir/sofosbuvir
      exhibits a favorable drug-drug interaction profile and can be administered with
      various medications that may be used by hepatitis C virus-infected patients,
      including patients with comorbidities, such as co-infection with human
      immunodeficiency virus or immunosuppression following liver transplantation.
      Ledipasvir/sofosbuvir is not expected to act as a victim or perpetrator of
      cytochrome P450- or UDP-glucuronosyltransferase 1A1-mediated drug-drug
      interactions. With the exception of strong inducers of P-glycoprotein, such as
      rifampin, ledipasvir/sofosbuvir is not expected to act as a victim of clinically
      relevant drug-drug interactions. As a perpetrator of pharmacokinetic drug-drug
      interactions via P-glycoprotein/BCRP, ledipasvir/sofosbuvir should not be used
      with rosuvastatin and elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil
      fumarate, whereas its co-administration with amiodarone is not recommended
      because of a pharmacodynamic interaction. This review summarizes a number of drug
      interaction studies conducted in support of the clinical development of
      ledipasvir/sofosbuvir.

PMID- 29644538
TI  - A Review of the Clinical Usefulness of Selective Laser Trabeculoplasty in
      Exfoliative Glaucoma.
AB  - In the last decade, selective laser trabeculoplasty (SLT) has been commonly used
      in the management of several different types of glaucoma, as either primary or
      adjunct therapy. The technique has an excellent safety profile and is at least as
      effective as argon laser trabeculoplasty. Although the actual mechanism of action
      of SLT remains unclear, evidence has shown that it does not induce
      morphologically evident trabecular meshwork alterations. SLT's non-disruptive
      mode of action offers the advantage of repeatability. Exfoliation glaucoma (XFG)
      is a secondary open-angle glaucoma with unfavorable intraocular pressure (IOP)
      characteristics, which typically carries a poorer long-term prognosis than
      primary open-angle glaucoma. Consequently, patients with XFG often need multiple
      medications to achieve IOP levels that prevent disease progression. Because
      complicated pharmacotherapy regimens undermine the long-term tolerability and
      compliance of patients with XFG, options such as SLT may decrease the burden of
      multiple therapies and ultimately improve prognosis. In fact, SLT may be a
      particularly attractive option in XFG because the pigment-laden trabecular tissue
      of these patients enhances the absorption of laser energy and thus augments the
      biologic effects induced by this treatment. The current article reviews the
      postulated mechanisms of action of SLT, discusses practical aspects of SLT
      therapy, and examines selected peer-reviewed literature pertaining to the
      clinical usefulness of this modality in XFG patients.

PMID- 29644539
TI  - Incidence, Prevalence, and Survival of Patients with Idiopathic Pulmonary
      Fibrosis in the UK.
AB  - INTRODUCTION: Recent developments in the care of patients with idiopathic
      pulmonary fibrosis have the potential to improve survival rates. Population-based
      estimates of the current disease burden are needed to evaluate the future impact
      of newly approved therapies. The objective of this study is to describe
      incidence, prevalence, and survival of idiopathic pulmonary fibrosis patients in
      the UK. METHODS: Between 2000 and 2012, a patient cohort (N = 9,748,108),
      identified from Clinical Practice Research Datalink primary care data, was used
      to identify incident and prevalent cases of idiopathic pulmonary fibrosis
      clinical syndrome. Incident cases were followed up to identify deaths. Poisson
      and Cox regressions were used to calculate incidence rate ratios (IRR) and hazard
      ratios for mortality, respectively. Adjustments were made for age, gender, and
      strategic health authority. Survival from diagnosis was estimated using Kaplan
      Meier analysis. RESULTS: In total 1491 and 4527 incident cases were identified
      using narrow and broad idiopathic pulmonary fibrosis-clinical syndrome
      definitions, respectively. Incidence and prevalence increased during the study.
      Compared with 2000, a near 80% increase in incidence was observed by 2012 [IRR
      1.78 (95% CI 1.50-2.11; broad definition)], despite an observed decrease using
      the narrow definition [0.50 (0.38-0.65)]. Median survival was 3.0 years (95% CI
      2.8-3.1) and 2.7 years (95% CI 2.5-3.0) in broad (n = 2168) and narrow case sets
      (n = 996), respectively. No significant changes in survival were observed.
      CONCLUSIONS: Idiopathic pulmonary fibrosis incidence rates have increased since
      2000 and survival remains poor. These results provide a benchmark against which
      the effects of future treatment changes can be measured. FUNDING: InterMune UK
      and Ireland (now part of F. Hoffman La Roche).

PMID- 29644541
TI  - Prevalence of the systemic inflammatory response syndrome in patients who
      underwent orthognathic surgery.
AB  - PURPOSE: The systemic inflammatory response syndrome (SIRS) is the body's
      response to an insult, such as infection, trauma, burn, and surgical stress
      linked to several factors deemed potential for multiple organ failure if left
      untreated. Thus, the aim of this paper was a prospective study to examine the
      incidence of SIRS in postoperative patients who underwent orthognathic surgery
      from June/2013 to July/2016. METHODS: The sample consisted of 80 patients who
      underwent bimaxillary orthognathic surgery, with data on vital signs and white
      blood cell count collected preoperatively, and the same data collected in the
      immediate postoperative period, in addition to CO2 pressure in arterial blood by
      blood gas analysis. The data were tabulated and cases of SIRS (2 or more signs
      out of four pre-set signs) were identified within 24 h after surgery. RESULTS:
      From the sample of 80 patients, 26 (32.5% of total) patients had SIRS with higher
      incidence in females who are 40 years old. CONCLUSION: The incidence of patients
      who develop SIRS after orthognathic surgery is relatively high and we should pay
      attention to the possible complications that these cases can evolve.

PMID- 29644542
TI  - Challenges in inbreeding estimation of large populations based on Polish Holstein
      Friesian cattle pedigree.
AB  - The aim of this study was to evaluate observed and future inbreeding level in
      Polish Holstein-Friesian cattle population. In total, over 9.8 mln animals were
      used in the analysis coming from the pedigree of Polish Federation of Cattle
      Breeders and Dairy Farmers. Inbreeding level, as an average per birth year, was
      estimated with the method accounting for missing parent information with the
      assumption of year 1950 as the base year of the population. If an animal had no
      ancestral records, an average inbreeding level from its birth year was assigned.
      Twice the average inbreeding level served as relatedness of the animal to the
      population, which enabled estimation of inbreeding in its offspring. The future
      inbreeding of potential offspring was estimated as an average of animals (bulls
      and cows) available for mating in a certain year. It was observed that 30-50% of
      animals born between 1985 and 2015 had no relevant ancestral information, which
      is caused by a high number of new animals and/or entire farms entering the
      national milk recordings. For the year 2015, the observed inbreeding level was
      3.30%, which was more than twice the inbreeding with the classical approach
      (without missing parent information) and higher by 0.4% than the future
      inbreeding. The average increase of inbreeding in years 2010-2015 was 0.10%,
      which is similar to other countries monitored by World Holstein-Friesian
      Federation. However, the values might be underestimated due to low pedigree
      completeness. The estimates of future inbreeding suggested that observed
      inbreeding could be even lower and also increase slower, which indicates a
      constant need to monitor rate of increase in inbreeding over time. The most
      important aspect of presented results is the necessity to advise individual
      farmers to keep precise recordings of the matings on their farm in order to
      improve the pedigree completeness of Polish Holstein-Friesian and to use suitable
      mating programs to avoid too rapid growth of inbreeding.

PMID- 29644540
TI  - Molecular epidemiology of carbapenem-resistant Pseudomonas aeruginosa in an
      endemic area: comparison with global data.
AB  - Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is an endemic problem in
      certain countries including Greece. CRPA and multidrug-resistant P. aeruginosa
      (MDRPA) firstly emerged in our region during the 80s, right after the launch of
      imipenem and meropenem as therapeutic agents against P. aeruginosa infections.
      The role of outer membrane protein (Opr) inactivation has been known to
      contribute to imipenem resistance since many years, while efflux overexpression
      systems have been mainly associated with meropenem resistance. Among
      carbapenemases, metallo-beta-lactamases (MBL) and mostly Verona integron-mediated
      (VIM) MBL's have played the most crucial role in CRPA emergence. VIM-2 and VIM-4
      producing CRPA, usually belonging to clonal complexes (CC) 111 and 235
      respectively, have most frequently been isolated. BlaVIM-2 and blaVIM-4 are
      usually associated with a class 1 integron. VIM-17 also has appeared in Greece.
      On the other hand, other VIM subtypes detected in a global level, such as VIM-3,
      VIM-5, VIM-6, VIM-7, VIM-11, VIM-14, VIM-15, VIM-16 and VIM-18 have not yet
      emerged in Greece. However, new VIM subtypes will probably emerge in the future.
      In addition, MBL carbapenemases other than VIM, detected worldwide have not yet
      appeared. A single CRPA isolate producing KPC has emerged in our region several
      years ago. The study of the molecular basis of Opr deficiency and efflux
      overexpression remains a challenge for the future. In this article, we review the
      molecular epidemiology of CRPA in an endemic area, compared to global data.

PMID- 29644543
TI  - Bioaccumulation of sediment-associated substituted phenylamine antioxidants in
      Tubifex tubifex and Lampsilis siliquoidea.
AB  - Substituted phenylamine antioxidants (SPAs) are additives in a variety of
      commercial polymers (e.g., lubricants, plastics, etc.). Based on their
      physicochemical properties, if SPAs were to enter an aquatic system, they would
      likely partition into sediment and have the capacity to bioaccumulate in biota.
      This study investigated the potential of four sediment-associated SPAs,
      diphenylamine (DPA), N-phenyl-1-naphthalene (PNA), N-(1,3-dimethylbutyl)-N'
      phenyl-1,4-phenylenediamine (DPPDA), and 4,4'-methylene-bis[N-sec-butylaniline]
      (MBA) to accumulate in the tissues of freshwater mussels (Lampsilis siliquoidea)
      and oligochaete worms (Tubifex tubifex). Mussels and worms were exposed to
      sediment spiked with individual SPAs for 28 d. The concentration of SPAs was
      measured in the gill, gonad, and remaining viscera of the mussels and entire body
      of the worms. The majority of biota-sediment accumulation factors (28-d BSAFs)
      for the different tissues of mussels were < 1. The highest concentrations of SPAs
      were consistently observed in the gill tissue of mussels relative to the gonad
      and viscera. The 28-d BSAFs for DPPDA and MBA for worms were < 1, and for DPA and
      PNA, they ranged from 0.38-2.13 and 1.54-33.24, respectively. The higher 28-d
      BSAFs observed for worms compared to mussels were likely because worms are
      endobenthic and feed on sediment-associated organic matter. PNA and DPPDA have
      similar octanol-water partition coefficients (Kow) but greater 28-d BSAFs were
      observed for PNA compared to DPPDA for both species. This observation provides
      evidence that biota may be able to metabolize and/or excrete SPAs with similar
      physicochemical properties at considerably different rates. The 28-d BSAFs
      observed for sediment-associated SPAs are lower than those typically required for
      a chemical to be classified as bioaccumulative.

PMID- 29644544
TI  - Toxicity of flavor enhancers to the oriental fruit fly, Bactrocera dorsalis
      (Hendel) (Diptera: Tephritidae).
AB  - The objective of this study was to evaluate the toxicity of flavor enhancers to
      the oriental fruit fly Bactrocera dorsalis (Hendel). The flavor enhancers
      glycine, disodium guanylate, succinic acid disodium salt, monosodium glutamate
      (MSG), disodium inosinate, and L-alanine significantly increased the mortality of
      B. dorsalis flies. The mortality of flies that fed on glycine, disodium
      guanylate, succinic acid disodium salt, and MSG was greater than 90%.
      Additionally, fruit fly mortality increased with increases in both time and
      concentration. Glycine not only reduced the climbing ability of B. dorsalis but
      also affected the duration and frequency of its behavioral patterns (flight,
      walking, grooming and inactivity). Compared with adult flies in the control
      group, adult B. dorsalis flies that fed on glycine exhibited a significantly
      increased duration and frequency of inactivity and a decreased duration and
      frequency of both flight and walking. However, the effect of glycine on grooming
      activity was not significant. These findings demonstrate the toxic effects of
      flavor enhancers on B. dorsalis. Glycine also affected the behavior of adult
      flies at a low dose. Therefore, glycine has potentially toxic to insects and also
      likely to have a negative impact at sublethal concentrations.

PMID- 29644545
TI  - Adaptive Recruitment and Parenting Interventions for Immigrant Latino Families
      with Adolescents.
AB  - Parenting programs are an effective strategy to prevent multiple risky outcomes
      during adolescence. However, these programs usually enroll one caregiver and have
      low attendance. This study evaluated the preliminary results, cost, and
      satisfaction of adaptive recruitment and parenting interventions for immigrant
      Latino families. A mixed methods study was conducted integrating a pre-post
      design with embedded qualitative and process evaluations. Fifteen immigrant
      Latino families with an adolescent child aged 10-14 were recruited. Two-caregiver
      families received a home visit to increase enrollment of both caregivers. All
      families participated in an adaptive parenting program that included group
      sessions and a one-to-one component (online videos plus follow-up telephone
      calls) for those who did not attend the group sessions. The intervention
      addressed positive parenting practices using a strengths-based framework. Primary
      outcomes were the proportion of two-parent families recruited and intervention
      participation. Secondary outcomes were change in parenting self-efficacy,
      practices, fidelity, costs, and satisfaction. Participants completed
      questionnaires and interaction tasks before and after participating in the
      intervention. In addition, participants and program facilitators completed
      individual interviews to assess satisfaction with the program components.
      Overall, 23 parents participated in the intervention; 73% of two-parent families
      enrolled with both parents. Most participants completed 75% or more of the
      intervention. Fathers were more likely to use the one-to-one component of the
      intervention than mothers (p = .038). Participants were satisfied with program
      modifications. In sum, adaptive recruitment and parenting interventions achieved
      high father enrollment and high participation. These findings warrant further
      evaluation in randomized trials.

PMID- 29644546
TI  - Imaging of urgencies and emergencies in the lung cancer patient.
AB  - : Lung cancer patients often experience potentially life-threatening medical
      urgencies and emergencies, which may be a direct or indirect result of the
      underlying malignancy. This pictorial review addresses the most common thoracic,
      neurological and musculoskeletal medical emergencies in lung cancer patients,
      including superior vena cava syndrome, pulmonary embolism, spontaneous
      pneumothorax, cardiac tamponade, massive haemoptysis, central airway obstruction,
      oesophagorespiratory fistula, malignant spinal cord compression, carcinomatous
      meningitis, cerebral herniation and pathological fracture. Emphasis is placed on
      imaging findings, the role of different imaging techniques and a brief discussion
      of epidemiology, pathophysiology and therapeutic options. Since early diagnosis
      is important for adequate patient management and prognosis, radiologists have a
      crucial role in recognising and communicating these urgencies and emergencies.
      TEACHING POINTS: * Multiplanar multidetector computed tomography is the imaging
      examination of choice for thoracic urgencies and emergencies. * Magnetic
      resonance imaging is the imaging modality of choice for investigating central
      nervous system emergencies. * Urgencies and emergencies can be the initial
      manifestation of lung cancer. * Radiologists have a crucial role in recognising
      and in communicating these urgencies/emergencies.

PMID- 29644547
TI  - SACMDA: MiRNA-Disease Association Prediction with Short Acyclic Connections in
      Heterogeneous Graph.
AB  - MiRNA-disease association is important to disease diagnosis and treatment.
      Prediction of miRNA-disease associations is receiving increasing attention. Using
      the huge number of known databases to predict potential associations between
      miRNAs and diseases is an important topic in the field of biology and medicine.
      In this paper, we propose a novel computational method of with Short Acyclic
      Connections in Heterogeneous Graph (SACMDA). SACMDA obtains AUCs of 0.8770 and
      0.8368 during global and local leave-one-out cross validation, respectively.
      Furthermore, SACMDA has been applied to three important human cancers for
      performance evaluation. As a result, 92% (Colon Neoplasms), 96% (Carcinoma
      Hepatocellular) and 94% (Esophageal Neoplasms) of top 50 predicted miRNAs are
      confirmed by recent experimental reports. What's more, SACMDA could be
      effectively applied to new diseases and new miRNAs without any known
      associations, which overcomes the limitations of many previous methods.

PMID- 29644548
TI  - Rheology of granular materials composed of crushable particles.
AB  - We investigate sheared granular materials composed of crushable particles by
      means of contact dynamics simulations and the bonded-cell model for particle
      breakage. Each particle is paved by irregular cells interacting via cohesive
      forces. In each simulation, the ratio of the internal cohesion of particles to
      the confining pressure, the relative cohesion, is kept constant and the packing
      is subjected to biaxial shearing. The particles can break into two or more
      fragments when the internal cohesive forces are overcome by the action of
      compressive force chains between particles. The particle size distribution
      evolves during shear as the particles continue to break. We find that the
      breakage process is highly inhomogeneous both in the fragment sizes and their
      locations inside the packing. In particular, a number of large particles never
      break whereas a large number of particles are fully shattered. As a result, the
      packing keeps the memory of its initial particle size distribution, whereas a
      power-law distribution is observed for particles of intermediate size due to
      consecutive fragmentation events whereby the memory of the initial state is lost.
      Due to growing polydispersity, dense shear bands are formed inside the packings
      and the usual dilatant behavior is reduced or cancelled. Hence, the stress-strain
      curve no longer passes through a peak stress, and a progressive monotonic
      evolution towards a pseudo-steady state is observed instead. We find that the
      crushing rate is controlled by the confining pressure. We also show that the
      shear strength of the packing is well expressed in terms of contact anisotropies
      and force anisotropies. The force anisotropy increases while the contact
      orientation anisotropy declines for increasing internal cohesion of the
      particles. These two effects compensate each other so that the shear strength is
      nearly independent of the internal cohesion of particles.

PMID- 29644550
TI  - Distinctive and Complementary MS2 Fragmentation Characteristics for
      Identification of Sulfated Sialylated N-Glycopeptides by nanoLC-MS/MS Workflow.
AB  - High sensitivity identification of sulfated glycans carried on specific sites of
      glycoproteins is an important requisite for investigation of molecular
      recognition events involved in diverse biological processes. However, aiming for
      resolving site-specific glycosylation of sulfated glycopeptides by direct LC-MS2
      sequencing is technically most challenging. Other than the usual limiting factors
      such as lower abundance and ionization efficiency compared to analysis of non
      glycosylated peptides, confident identification of sulfated glycopeptides among
      the more abundant non-sulfated glycopeptides requires additional considerations
      in the selective enrichment and detection strategies. Metal oxide has been
      applied to enrich phosphopeptides and sialylated glycopeptides, but its use to
      capture sulfated glycopeptides has not been investigated. Likewise, various
      complementary MS2 fragmentation modes have yet to be tested against sialylated
      and non-sialylated sulfoglycopeptides due to limited appropriate sample
      availability. In this study, we have investigated the feasibility of sequencing
      tryptic sulfated N-glycopeptide and its MS2 fragmentation characteristics by
      first optimizing the enrichment methods to allow efficient LC-MS detection and
      MS2 analysis by a combination of CID, HCD, ETD, and EThcD on hybrid and tribrid
      Orbitrap instruments. Characteristic sulfated glyco-oxonium ions and direct loss
      of sulfite from precursors were detected as evidences of sulfate modification. It
      is anticipated that the technical advances demonstrated in this study would allow
      a feasible extension of our sulfoglycomic analysis to sulfoglycoproteomics.
      Graphical Abstract ?.

PMID- 29644549
TI  - Cracking the Sugar Code by Mass Spectrometry : An Invited Perspective in Honor of
      Dr. Catherine E. Costello, Recipient of the 2017 ASMS Distinguished Contribution
      Award.
AB  - The structural study of glycans and glycoconjugates is essential to assign their
      roles in homeostasis, health, and disease. Once dominated by nuclear magnetic
      resonance spectroscopy, mass spectrometric methods have become the preferred
      toolbox for the determination of glycan structures at high sensitivity. The
      patterns of such structures in different cellular states now allow us to
      interpret the sugar codes in health and disease, based on structure-function
      relationships. Dr. Catherine E. Costello was the 2017 recipient of the American
      Society for Mass Spectrometry's Distinguished Contribution Award. In this
      Perspective article, we describe her seminal work in a historical and
      geographical context and review the impact of her research accomplishments in the
      field.8 ? Graphical abstract.

PMID- 29644551
TI  - Lipase catalyzed epoxidation of fatty acid methyl esters derived from unsaturated
      vegetable oils in absence of carboxylic acid.
AB  - Nowadays the industrial chemistry reactions rely on green technologies. Enzymes
      as lipases are increasing its use in diverse chemical processes. Epoxidized fatty
      acid methyl esters obtained from transesterification of vegetable oils have
      recently found applications as polymer plasticizer, agrochemical, cosmetics,
      pharmaceuticals and food additives. In this research article, grapeseed, avocado
      and olive oils naturally containing high percents of mono and poly unsaturations
      were used as starting materials for the production of unsaturated fatty acid
      methyl esters. The effect of lauric acid as an active oxygen carrier was studied
      on epoxidation reactions where unsaturated fatty acid methyl esters were
      converted to epoxy fatty acid methyl esters using immobilized Candida antarctica
      Lipase type B as catalyst and hydrogen peroxide as oxygen donor at mild
      temperature and pressure conditions. After this study it was confirmed by 1H NMR,
      13C NMR and GC-MS that the addition of lauric acid to the enzymatic reaction is
      unnecessary to transform the alkenes in to epoxides. It was found that
      quantitative conversions were possible in despite of a carboxylic acid absence.

PMID- 29644552
TI  - Healthcare Services Utilization Among Migrants in Portugal: Results From the
      National Health Survey 2014.
AB  - Migrants' health is attracting substantial global interest. We aimed to identify
      barriers and differences in healthcare services utilization between migrants and
      natives in a nationally representative sample using data from the National Health
      Survey 2014. A total of 18,165 participants providing information on country of
      birth and nationality were included, and comparison of healthcare services
      utilization was made by using participants born in Portugal and with Portuguese
      nationality as the reference group. Migrants reported a lower frequency of
      medical visits, a higher consumption of medication without a prescription and
      less use of preventive care services. The main reasons for not attending medical
      consultations among migrants were the absence of need and financial difficulties.
      This study illustrates inequalities in healthcare use among migrants in Portugal,
      and provides useful information for enlightening policymakers and healthcare
      providers to develop health policies that can address migrants' needs.

PMID- 29644553
TI  - Theory and methodology: essential tools that can become dangerous belief systems.

PMID- 29644554
TI  - Curcumin ameliorates palmitate-induced inflammation in skeletal muscle cells by
      regulating JNK/NF-kB pathway and ROS production.
AB  - Curcumin, a natural polyphenol compound, has the beneficial effects on several
      diseases such as metabolic syndrome, cancer, and diabetes. The anti-inflammatory
      property of curcumin has been demonstrated in different cells; however, its role
      in prevention of palmitate-induced inflammation in skeletal muscle C2C12 cells is
      not known. In this study, we examined the effect of curcumin on the inflammatory
      responses stimulated by palmitate in C2C2 cells. The results showed that
      palmitate upregulated the mRNA expression and protein release of IL-6 and TNF
      alpha cytokines in C2C12 cells, while pretreatment with curcumin was able to
      attenuate the effect of palmitate on inflammatory cytokines. The anti
      inflammatory effect of curcumin was associated with the repression of
      phosphorylation of IKKalpha-IKKbeta, and JNK. Palmitate also caused an increase
      in reactive oxygen species (ROS) level that curcumin abrogated it. Collectively,
      these findings suggest that curcumin may represent a promising therapy for
      prevention of inflammation in skeletal muscle cells.

PMID- 29644555
TI  - A mechanistic approach to explore the neuroprotective potential of zonisamide in
      seizures.
AB  - BACKGROUND: Epilepsy, a disease of the brain, is one of the most common serious
      neurological conditions. It is associated with a group of processes which alter
      energy metabolism, interrupt cellular ionic homeostasis, cause receptor
      dysfunction, activate inflammatory cascade, alter neurotransmitter uptake and
      result in neuronal damage. The increasing knowledge and understanding about the
      basis of neuronal changes in epilepsy lead to investigate the mechanistic pathway
      of neuroprotective agents in epilepsy. With this background, the present study is
      designed to reveal the molecular and biochemical mechanisms involved in the
      neuroprotective potential of zonisamide in epilepsy. METHODS: Seizure-induced
      neuronal damage was produced by maximal electroshock seizures in animals. The
      oxidative stress and neuroinflammatory and apoptotic markers were assessed in the
      brain tissue of animals. RESULTS AND DISCUSSION: The present findings revealed
      that zonisamide treatment prevented the development of seizures in animals.
      Seizures-induced free radicals production and neuroinflammation were markedly
      ameliorated by zonisamide administration. In conclusion, the present study
      demonstrated the mechanisms behind the strong neuroprotective potential of
      zonisamide against seizures by attenuating the oxidative stress, inflammatory
      cascade and neuronal death associated with progression of seizures. It can be
      further developed as a neuroprotective agent for epilepsy and other
      neurodegenerative disorders.

PMID- 29644556
TI  - Postoperative Pain and Opioid Consumption in the Acute Postoperative Period after
      Laparoscopic Gastrectomy.

PMID- 29644558
TI  - Finger and forehead photoplethysmography-derived pulse-pressure variation and the
      benefits of baseline correction.
AB  - To non-invasively predict fluid responsiveness, respiration-induced pulse
      amplitude variation (PAV) in the photoplethysmographic (PPG) signal has been
      proposed as an alternative to pulse pressure variation (PPV) in the arterial
      blood pressure (ABP) signal. However, it is still unclear how the performance of
      the PPG-derived PAV is site-dependent during surgery. The aim of this study is to
      compare finger- and forehead-PPG derived PAV in their ability to approach the
      value and trend of ABP-derived PPV. Furthermore, this study investigates four
      potential confounding factors, (1) baseline variation, (2) PPV, (3) ratio of
      respiration and heart rate, and (4) perfusion index, which might affect the
      agreement between PPV and PAV. In this work, ABP, finger PPG, and forehead PPG
      were continuously recorded in 29 patients undergoing major surgery in the
      operating room. A total of 91.2 h data were used for analysis, from which PAV and
      PPV were calculated and compared. We analyzed the impact of the four factors
      using a multiple linear regression (MLR) analysis. The results show that compared
      with the ABP-derived PPV, finger-derived PAV had an agreement of 3.2 +/- 5.1%,
      whereas forehead-PAV had an agreement of 12.0 +/- 9.1%. From the MLR analysis, we
      found that baseline variation was a factor significantly affecting the agreement
      between PPV and PAV. After correcting for respiration-induced baseline variation,
      the agreements for finger- and forehead-derived PAV were improved to reach an
      agreement of - 1.2 +/- 3.8% and 3.3 +/- 4.8%, respectively. To conclude, finger
      derived PAV showed better agreement with ABP-derived PPV compared to forehead
      derived PAV. Baseline variation was a factor that significantly affected the
      agreement between PPV and PAV. By correcting for the baseline variation, improved
      agreements were obtained for both the finger and forehead, and the difference
      between these two agreements was diminished. The tracking abilities for both
      finger- and forehead-derived PAV still warrant improvement for wide use in
      clinical practice. Overall, our results show that baseline-corrected finger- and
      forehead-derived PAV may provide a non-invasive alternative for PPV.

PMID- 29644557
TI  - Colorectal Liver Metastases: Does the Future of Precision Medicine Lie in Genetic
      Testing?
AB  - Colorectal liver metastases (CRLM) present an important clinical challenge in
      both surgical and medical oncology. Despite improvements in management, survival
      among patients undergoing resection of CRLM is still very variable and there is a
      paucity of clinical trial data and reliable biomarkers that could guide
      prognostic forecasts, treatment selection, and follow-up. Fortunately, recent
      advances in molecular biology and tumor sequencing have identified a number of
      critical genetic loci and proliferation markers that may hold the key to
      understanding the biologic behavior of CRLM; specifically, mutations of KRAS,
      BRAF, TP53, PIK3CA, APC, expression of Ki-67, and the presence of microsatellite
      instability appear to have a decisive impact on prognosis and response to
      treatment in patients with CRLM. While the applicability of genetic biomarkers in
      everyday clinical practice remains conditional on the development of inexpensive
      bedside sequencing, targeted therapies, and the conduct of appropriate clinical
      trials, the promise of personalized treatment may be closer to realization than
      ever before.

PMID- 29644559
TI  - A versatile Trichoderma reesei expression system for the production of
      heterologous proteins.
AB  - OBJECTIVES: To develop a versatile Trichoderma reesei (teleomorph Hypocrea
      jecorina) expression system for the high-purity production of heterologous
      proteins. RESULTS: The versatile T. reesei expression system is based on xyn1 and
      xyn2 promoters, A824V transition in XYRI, and a bicomponent carbon source
      strategy. Red fluorescent protein gene rfp and alkaline endoglucanase EGV gene
      egv3 from Humicola insolens were used as reporter genes to test our versatile
      expression system CONCLUSIONS: The versatile T. reesei expression system can be
      applied to produce heterologous proteins with high purity and high yield.

PMID- 29644560
TI  - Correction to: Association between lifestyle, menstrual/reproductive history, and
      histological factors and risk of breast cancer in women biopsied for benign
      breast disease.
AB  - The third category for extent of involution in Table 4 was published incorrectly
      in the original publication. The correct classification is >= 75% and the
      corrected Table 4 is given in the Correction article.

PMID- 29644562
TI  - Exacerbating Inequalities? Health Policy and the Behavioural Sciences.
AB  - There have been calls for some time for a new approach to public health in the
      United Kingdom and beyond. This is consequent on the recognition and acceptance
      that health problems often have a complex and multi-faceted aetiology. At the
      same time, policies which utilise insights from research in behavioural economics
      and psychology ('behavioural science') have gained prominence on the political
      agenda. The relationship between the social determinants of health (SDoH) and
      behavioural science in health policy has not hitherto been explored. Given the on
      going presence of strategies based on findings from behavioural science in policy
      making on the political agenda, an examination of this is warranted. This paper
      begins by looking at the place of the SDoH within public health, before
      outlining, in brief, the recent drive towards utilising behavioural science to
      formulate law and public policy. We then examine the relationship between this
      and the SDoH. We argue that behavioural public health policy is, to a certain
      extent, blind to the social and other determinants of health. In section three,
      we examine ways in which such policies may perpetuate and/or exacerbate health
      inequities and social injustices. We argue that problems in this respect may be
      compounded by assumptions and practices which are built into some behavioural
      science methodologies. We also argue that incremental individual gains may not be
      enough. As such, population-level measures are sometimes necessary. In section
      four we defend this contention, arguing that an equitable and justifiable public
      health requires such measures.

PMID- 29644561
TI  - Osteoprotegerin deficiency causes morphological and quantitative damage in
      epithelial rests of Malassez.
AB  - Epithelial rests of Malassez (ERM), the only odontogenic epithelial structures in
      periodontal tissue, are proposed to correlate with root resorption, but the
      detailed mechanism remains unclear. Osteoprotegerin (OPG), the main inhibitor of
      osteoclastogenesis, plays a pivotal role in inhibiting root resorption, and ERM
      cells express OPG mRNA in vitro. Thus, in this study, we aimed to clarify OPG
      expression in ERM in vivo and to explore the role of OPG in ERM to determine
      whether ERM are associated with root resorption via OPG. We established Opg
      knockout (Opg-KO) mice and detected the OPG expression in ERM by
      immunohistochemical staining in 4-, 6-, 10-, 26- and 52-week-old mice. The ERM of
      wild-type (WT) mice and Opg-KO mice were evaluated histologically at 4, 10 and 26
      weeks of age. Orthodontic root resorption models were established, maxillae were
      collected after 4 weeks, and ERM were analysed by histomorphometric analysis. In
      our study, OPG displayed sustained expression in ERM, and OPG deficiency caused
      the destruction of ERM, characterized by irregular morphology and reduced
      numbers. Moreover, after orthodontic treatment, the loss of OPG severely damaged
      ERM, aggravating root resorption. Together, our results demonstrated that ERM
      expressed the OPG protein in vivo and that OPG deficiency resulted in
      morphological and quantitative damage to ERM. Furthermore, ERM may be associated
      with root resorption via OPG, thus helping to explain the mechanism underlying
      root resorption.

PMID- 29644563
TI  - Heat acclimation increases mitochondrial respiration capacity of C2C12 myotubes
      and protects against LPS-mediated energy deficit.
AB  - This work investigated the effect of a 6-day heat acclimation (HA) protocol on
      myotube metabolic responses at baseline and in response to a subsequent
      lipopolysaccharide (LPS) challenge. C2C12 myotubes were incubated for 2 h/day at
      40  degrees C for 6 days (HA) or maintained at 37  degrees C (C). Following 24-h
      recovery, myotubes were challenged with 500 ng/ml LPS for 2 h, then collected for
      analysis of protein markers of mitochondrial biogenesis and macronutrient
      storage. Functional significance of these changes was confirmed with
      mitochondrial respiration and glycolytic measurements on a Seahorse XF-96
      analyzer. HA stimulated mitochondrial biogenesis and increased indicators of
      mitochondrial content [SIRT1 (+ 62%); PGC-1alpha (+ 57%); NRF-1 (+ 40%); TFAM (+
      141%); CS (+ 25%); CytC (+ 38%); all p < 0.05]. Altered lipid biosynthesis
      enzymes [p-ACCa:ACC (+ 59%; p = 0.04) and FAS (- 86%; p < 0.01)] suggest fatty
      acid generation may have been downregulated, whereas increased GLUT4 (+ 69%; p <
      0.01) and LDH-B (+ 366%; p < 0.01) suggest aerobic glycolytic capacity may have
      been improved. Mitochondrial biogenesis signaling in HA myotubes was suppressed
      by 500 ng/ml LPS (PGC-1alpha, NRF-1, TFAM; all p > 0.05) but increased LDH-B (+
      30%; p = 0.02) and CPT-1 (+ 55%; p < 0.01) suggesting improved catabolic
      function. Basal respiration was increased in HA myotubes (+ 8%; p < 0.01) and HA
      myotubes maintained elevated basal respiration during LPS challenge (+ 8%; p <
      0.01). LPS reduced peak respiration in C myotubes (- 6%; p < 0.01) but did not
      impair peak respiration in HA myotubes (p > 0.05). Oxidative reliance was
      elevated in HA over that in control (+ 25%; p < 0.01) and in HA + LPS over C +
      LPS (+ 30%; p < 0.01). In summary, HA stimulated mitochondrial biogenesis in
      C2C12 myotubes. HA myotubes exhibited (1) elevated basal/peak mitochondrial
      respiration capacities; (2) greater oxidative reliance; and (3) protection
      against LPS-mediated respiration impairment. Collectively, these data suggest HA
      may improve aerobic metabolism in skeletal muscle and protect against LPS
      mediated energy deficit.

PMID- 29644564
TI  - Semi-quantitative Cough Strength Score as a Predictor for Extubation Outcome in
      Traumatic Brain Injury: A Prospective Observational Study.
AB  - BACKGROUND: Between 25 and 40% of extubated patients with traumatic brain injury
      (TBI) in the intensive care unit at our hospital (Assiut University Hospital
      Assiut-Egypt) require reintubation. This reflects the importance of developing
      better criteria for predicting successful extubation in TBI. We evaluated the
      accuracy of semi-quantitative cough strength score (SCSS) and Glasgow coma scale
      (GCS) in predicting extubation outcomes in TBI. METHODS: This prospective
      observational study included patients (18-65 years), with TBI on mechanical
      ventilation more than 24 h who were ready to be weaned off. Three tools were
      used. Tool I: Patient assessment sheet, this tool used to assess socio
      demographic and clinical data of patients. Tool II: Semi-quantitative cough
      strength score (0-5). Tool III: Factors affecting successful extubation, this
      tool used to confirm the presence or absence of factors that can interfere with
      the results of extubation outcomes. After extubation, patient was followed up for
      72 h to check for extubation success. Multivariate logistic binary regression
      test was used to calculate odds ratio for different clinical data collected
      before extubation as independent factors and successful extubation as a dependent
      factor. RESULTS: Among 80 patients of mean age 40.6 (+/- 16.1), 34% were female,
      median admission GCS was 8 (4-13), extubation occurred on mean post-injury day
      6.5 (+/- 4), and 46.3% required reintubation. Successfully extubated patients had
      higher semi-quantitative cough scores and GCS. 81.3% patients with SCSS 5 were
      successfully extubated, while all patients with SCSS 0 were reintubated. All
      patients with GCS 15 were successfully extubated, and all patients with GCS < 12
      required intubation. CONCLUSION: SCSS has shown promise in predicting successful
      extubation in TBI.

PMID- 29644565
TI  - Genetic evaluation of growth in farmers' flocks of Madras Red sheep under long
      term selection in a group breeding scheme.
AB  - The Network Project on Sheep Improvement (NWPSI)-Madras Red field unit is a group
      breeding scheme involving 198 farmers' flocks of Madras Red sheep in which
      selection for growth traits and rotation of rams have been practised for over two
      decades. Growth data collected from these flocks were used to evaluate the
      performance and understand the direct and expected responses to selection based
      on genetic parameters. The body weight at birth (BW), weaning weight (WW), 6
      month weight (6W), 9-month weight (9W), 12-month weight (YW), pre-weaning average
      daily gain (ADG1, birth to 3 months), post-weaning ADG2 (3-6 months), ADG3 (6-9
      months), ADG4 (9-12 months) and ADG5 (3-12 months) were 2.67, 10.05, 14.56,
      18.36, 21.36, 80.13, 49.05, 43.00, 34.21 and 41.18 g, respectively. Univariate
      analyses were carried out using animal and sire models to estimate variance
      components. Heritability obtained from animal model for BW was 0.36 and the
      values for other body weight traits were almost unity. Heritability estimate for
      pre-weaning ADG1 was 0.31. Very high genetic variability was observed in spite of
      long-term selection and this sustenance of variability is one of the main
      advantages of a group breeding scheme, combining several flocks of smaller size.
      An increasing genetic and phenotypic trend was noticed for almost all the traits
      studied. The expected responses calculated based on genetic parameters also
      indicated scope for improvement.

PMID- 29644566
TI  - Effects of enzyme supplementation on the nutrient, amino acid, and energy
      utilization efficiency of citrus pulp and hawthorn pulp in Linwu ducks.
AB  - The objective of this study was to evaluate the effects of enzyme supplementation
      on the nutrient, amino acid, and energy utilization efficiency of citrus pulp and
      hawthorn pulp as unusual feedstuffs in Linwu ducks. Forty ducks were assigned to
      each treatment group and fed diets with or without complex enzyme
      supplementation. All birds received the same quantity of raw material (60 g) via
      the force-feeding procedure. With the exception of leucine and phenylalanine,
      amino acid concentrations in hawthorn pulp were twice those in citrus pulp.
      Enzyme supplementation significantly increased apparent dry matter digestibility
      (ADM) of citrus pulp (P < 0.05), but had no significant effects (P > 0.05) on the
      apparent and true utilization rates of other nutrients, apparent metabolizable
      energy (AME), or true metabolizable energy (TME), from citrus pulp and hawthorn
      pulp by Linwu ducks. However, enzyme supplementation significantly increased (P <
      0.05) apparent gross energy, true gross energy, AME, and TME of hawthorn pulp for
      Linwu ducks. There were no differences in the apparent and true utilization rates
      of amino acids from citrus pulp (P > 0.56) between the groups, with the exception
      of arginine (P < 0.05). There was an increasing trend in the apparent and true
      utilization rates of alanine (P = 0.06) and tyrosine (P = 0.074) from citrus pulp
      with enzyme supplementation. The apparent and true utilization rates of threonine
      in hawthorn pulp were increased significantly (P < 0.05) following enzyme
      supplementation. The addition of exogenous enzymes improved the forage quality of
      citrus pulp and hawthorn pulp, which represent potential feed resources for
      husbandry production.

PMID- 29644567
TI  - How accurate is the data provided to the Irish hip fracture database?
AB  - National databases, such as the Irish Hip Fracture Database (IHFD), are known to
      contain inaccuracies. The coordination of services, national funding and future
      research rely on the integrity of the IHFD so as to avoid policy and budget
      planning being based on misrepresentative data. An audit was performed to assess
      the accuracy of the 2016 IHFD data collected in our trauma unit. The Hospital In
      Patient Enquiry (HIPE)-recorded fracture classification, IHFD-recorded fracture
      classification and IHFD-recorded operation performed for each hip fracture
      patient was identified. Each variable was compared with the classifications and
      procedures derived by the authors. Two hundred fifty-two cases were identified.
      The HIPE-recorded fracture classification was accurate in 29% of cases, and the
      IHFD-recorded fracture classification in 61% (p < 0.001). The IHFD-recorded
      operation performed was accurate in 76% of cases. Thirty-six cases (14%) were
      omitted by HIPE, and eight (3%) from the local IHFD (p < 0.001). Errors resulted
      from poor documentation, in determining the presence of fracture displacement,
      prosthesis coating and intramedullary nail length. Diagnoses and procedures were
      identified from ward and theatre logbooks that the data coordinator was unable to
      record. The data coordinator in our unit doubled the accuracy of the data, and
      reduced the rate of omitted cases by a factor of 4.5. Accuracy levels would be
      significantly improved with clear, thorough documentation by the medical team
      following education of junior surgical trainees on hip fracture classification
      and procedural coding. Inaccurate data has a negative effect on hospital
      reimbursement and compromises the integrity of the IHFD.

PMID- 29644568
TI  - Smiling faces and cash bonuses: Exploring common affective coding across positive
      and negative emotional and motivational stimuli using fMRI.
AB  - Although it is clear that emotional and motivational manipulations yield a strong
      influence on cognition and behaviour, these domains have mostly been investigated
      in independent research lines. Therefore, it remains poorly understood how far
      these affective manipulations overlap in terms of their underlying neural
      activations, especially in light of previous findings that suggest a shared
      valence mechanism across multiple affective processing domains (e.g., monetary
      incentives, primary rewards, emotional events). This is particularly interesting
      considering the commonality between emotional and motivational constructs in
      terms of their basic affective nature (positive vs. negative), but dissociations
      in terms of instrumentality, in that only reward-related stimuli are typically
      associated with performance-contingent outcomes. Here, we aimed to examine
      potential common neural processes triggered by emotional and motivational stimuli
      in matched tasks within participants using functional magnetic resonance imaging
      (fMRI). Across tasks, we found shared valence effects in the ventromedial
      prefrontal cortex and left inferior frontal gyrus (part of dorsolateral
      prefrontal cortex), with increased activity for positive and negative stimuli,
      respectively. Despite this commonality, emotion and reward tasks featured
      differential behavioural patterns in that negative valence effects (performance
      costs) were exclusive to emotional stimuli, while positive valence effects
      (performance benefits) were only observed for reward-related stimuli. Overall,
      our data suggest a common affective coding mechanism across different task
      domains and support the idea that monetary incentives entail signed basic valence
      signals, above and beyond the instruction to perform both gain and loss trials as
      accurately as possible to maximise the outcome.

PMID- 29644569
TI  - Evaluation and breeding application of six brown planthopper resistance genes in
      rice maintainer line Jin 23B.
AB  - BACKGROUND: The brown planthopper (BPH), an insect species that feeds on rice
      plants (Oryza sativa L.), is one of the most destructive insect pests of rice.
      BPH can be controlled with chemical pesticides, but they are expensive in terms
      of the cost and environmental hazards. Hence, utilization of resistance genes in
      resistant varieties is considered as a more economical and eco-friendly effective
      method for control. RESULTS: In this study, six dominant BPH-resistance genes
      (Bph3, Bph14, Bph15, Bph18, Bph20 and Bph21) were introduced into an elite indica
      rice cultivar Jin 23B using the marker-assisted selection (MAS) method of
      breeding. One line combining Bph14 and Bph15 and six single gene introgression
      lines were used to evaluate the gene effects based on three parameters: seedling
      and tillering resistance of the rice genotypes, honeydew weight, and BPH survival
      rate. Among all improved lines, combination of Bph14 and Bph15 had the largest
      effect in conferring resistance to BPH. Bioassays showed that the order of the
      gene effects was Bph14/Bph15 > Bph15 >= Bph14 >= Bph20 >= Bph21 >= Bph3 > Bph18 >
      none at the rice seedling stage. The pyramided or single-gene introgression lines
      showed enhanced resistance relative to the control. Furthermore, field trial data
      demonstrated that yields of improved Jin 23B lines were similar to the control
      under BPH-free field conditions. CONCLUSIONS: Each of the BPH resistance genes
      reduced BPH growth and development, and was effective at both the seedling and
      tillering growth stages. These lines can be used in rice hybrid and production in
      China.

PMID- 29644570
TI  - Psoriatic disease treatment nowadays: unmet needs among the "jungle of biologic
      drugs and small molecules".

PMID- 29644571
TI  - Potential Human Health Risk Assessment of Heavy Metals via Consumption of Root
      Tubers from Ogoniland, Rivers State, Nigeria.
AB  - This study was designed to investigate the concentration of heavy metals and
      their associated human health risk via consumption of root tubers cultivated in
      three major communities in Ogoniland, Rivers State, Nigeria. The concentration of
      heavy metals, especially, Cr and Pb in soil, indicates a moderate contamination
      (? 1.00 mg/kg) level. The concentrations of heavy metals in the root tubers
      Manihot esculenta, Colocasia esculenta, and Dioscorea alata harvested from Choba,
      Kpean, and Bodo City ranged from 0.20 +/- 0.01-0.84 +/- 0.04, 0.01 +/- 0.001-0.09
      +/- 0.02, 0.01 +/- 0.002-0.63 +/- 0.04, 2.11 +/- 0.03-11.8 +/- 2.12, and 6.30 +/-
      1.18-118.6 +/- 0.19 mg/kg for Cr, Pb, Ni, Mn, and Fe respectively, while Cd had
      the same value of 0.01 +/- 0.001 mg/kg in the three samples across the three
      sites. The bio-accumulation factor (BAF) for Cd was ? 1. The estimated daily
      intake were below the FAO/WHO permissible limit, while the target hazard quotient
      (THQ) has a trend of Mn> Fe> Pb> Cd> Ni> Cr, and were ? 1 for all the sampling
      areas. The HI values for M. esculenta for children in Choba, Kpean, and Bodo City
      were ? 1, indicating that children among the local populace were susceptible to
      heavy metals health risks. The carcinogenic risk (CR) value of Cr indicates that
      there was appreciable lifetime cancer risk for Cr as the CR value in all the
      sampling sites were ? 10-4. Furthermore, CR values of Ni and Cd were also within
      the predicted lifetime risks of carcinogens. Heavy metal contamination of root
      tubers cultivated in Ogoniland may posed a great health risk to local populace
      especially for children via consumption of root tubers.

PMID- 29644572
TI  - Low-Magnitude Forces for Bone Modeling and Remodeling in Dentofacial Orthopedics.
AB  - PURPOSE OF REVIEW: To examine the evidence in support of light continuous forces
      for enhancing bone adaptation (modeling and remodeling) in orthodontics and
      dentofacial orthopedics. RECENT FINDINGS: Clinical evidence suggests that light
      continuous orthodontic force can achieve physiologic expansion of the maxillary
      arch, but the long-term stability and the biological effects of the procedure are
      unclear. Compared to conventional orthodontic appliances that deliver heavy
      interrupted forces for tooth movement, the application of low-magnitude forces in
      animal models leads to anabolic modeling and remodeling of the alveolar bone in
      the path of orthodontic tooth movement. This results in dental translation and
      expansion of the alveolar process. Light continuous forces are preferable to
      heavy forces for more physiologic dentofacial orthopedics. The interaction of low
      magnitude loads with soft tissue posture achieves therapeutic adaptation of the
      craniofacial skeleton. The increasing emphasis on genomic medicine and
      personalized treatment planning should focus on low-magnitude loads in
      orthodontics and dentofacial orthopedics.

PMID- 29644573
TI  - Myeloid-specific targeting of Notch ameliorates murine renal fibrosis via reduced
      infiltration and activation of bone marrow-derived macrophage.
AB  - Macrophages play critical roles in renal fibrosis. However, macrophages exhibit
      ontogenic and functional heterogeneities, and which population of macrophages
      contributes to renal fibrosis and the underlying mechanisms remain unclear. In
      this study, we genetically targeted Notch signaling by disrupting the
      transcription factor recombination signal binding protein-Jkappa (RBP-J), to
      reveal its role in regulation of macrophages during the unilateral ureteral
      obstruction (UUO)-induced murine renal fibrosis. Myeloid-specific disruption of
      RBP-J attenuated renal fibrosis with reduced extracellular matrix deposition and
      myofibroblast activation, as well as attenuated epithelial-mesenchymal
      transition, likely owing to the reduced expression of TGF-beta. Meanwhile, RBP-J
      deletion significantly hampered macrophage infiltration and activation in
      fibrotic kidney, although their proliferation appeared unaltered. By using
      macrophage clearance experiment, we found that kidney resident macrophages made
      negligible contribution, but bone marrow (BM)-derived macrophages played a major
      role in renal fibrogenesis. Further mechanistic analyses showed that Notch
      blockade reduced monocyte emigration from BM by down-regulating CCR2 expression.
      Finally, we found that myeloid-specific Notch activation aggravated renal
      fibrosis, which was mediated by CCR2+ macrophages infiltration. In summary, our
      data have unveiled that myeloid-specific targeting of Notch could ameliorate
      renal fibrosis by regulating BM-derived macrophages recruitment and activation,
      providing a novel strategy for intervention of this disease.

PMID- 29644574
TI  - Erratum to: Percutaneous Mitral Valve Interventions and Heart Failure.

PMID- 29644575
TI  - Erratum to: Management of Bradyarrhythmias in Heart Failure: A Tailored Approach.

PMID- 29644577
TI  - The Impact of Dose and Simultaneous Use of Acid-Reducing Agents on the
      Effectiveness of Vemurafenib in Metastatic BRAF V600 Mutated Melanoma: a
      Retrospective Cohort Study.
AB  - BACKGROUND: The impact of dose and simultaneous use of acid-reducing agents
      (ARAs) on the effectiveness of vemurafenib is unknown. OBJECTIVES: To determine
      the association between progression of metastatic BRAF V600 mutated melanoma and
      (1) dose reductions of vemurafenib and (2) simultaneous use of vemurafenib and
      ARAs. PATIENT AND METHODS: A retrospective cohort study of 112 first-line
      vemurafenib users for melanoma was conducted (March 2012-March 2016), using
      electronic patient records and pharmacy dispensing records of a Dutch academic
      hospital. Cox regression analysis was used to estimate the risk of progression
      with full-dose (n = 64) versus reduced-dose vemurafenib (n = 48) and with
      simultaneous use of vemurafenib and ARAs (n = 35) versus vemurafenib alone (n =
      77). Analyses were adjusted for age and sex. RESULTS: In total, disease
      progression occurred in 55% of treated patients on vemurafenib, with a median
      progression-free survival of 6.0 (95% confidence interval [CI] 5.0-6.9) months.
      Compared to patients on vemurafenib alone, there was no increased risk of
      progression among patients requiring vemurafenib at a reduced dose or among
      patients receiving simultaneous therapy with vemurafenib and ARAs. In addition,
      there was no increased risk of progression among patients who used reduced-dose
      vemurafenib and ARAs versus those receiving full-dose vemurafenib as sole
      therapy. However, a tendency for progression was observed among patients who used
      full-dose vemurafenib and ARAs versus full-dose vemurafenib alone (adjusted
      hazard ratio [HRa] 2.37; 95% CI 0.97-5.76), which became statistically
      significant in a sensitivity analysis (HRa 4.56; 95% CI 1.51-13.75). CONCLUSIONS:
      There was no association between the use of vemurafenib in a reduced dose or the
      simultaneous use of vemurafenib and ARAs and the risk of progression. In
      addition, there was no association between the simultaneous use of vemurafenib in
      a reduced dose and ARAs and the risk of progression. However, patients tolerating
      full-dose vemurafenib simultaneously with ARAs might have an increased risk of
      progression. This finding requires prospective validation.

PMID- 29644576
TI  - The State of the Summer: a Review of Child Summer Weight Gain and Efforts to
      Prevent It.
AB  - PURPOSE OF REVIEW: Accumulating evidence shows that children in the USA gain
      weight more rapidly during the summer, when school is not in session. This
      narrative review spanning 2007 to 2017 summarizes efforts to characterize the
      problem, identify key determinants, and intervene to prevent excess summer weight
      gain. RECENT FINDINGS: Summer weight gain remains a concern for elementary-age
      youth. Few studies have examined its determinants, but unfavorable summertime
      shifts in diet, physical activity, sedentary time, screen media use, and sleep
      have been reported. Increased structure is thought to protect against summer
      weight gain. Interventions to support physical activity and nutrition during the
      summer show promise, though large-scale impact on weight outcomes remains to be
      seen. Supporting health behaviors during the summer remains a priority for
      obesity prevention researchers, practitioners, and policymakers. Strategies to
      expand access to structured programs and reach beyond such programs to improve
      behaviors at home are of particular importance.

PMID- 29644578
TI  - Functional MRI and laser-evoked potentials evaluation in Charcot-Marie-Tooth
      syndrome.
AB  - Charcot-Marie-Tooth (CMT) disease is a genetically heterogeneous group of
      disorders. Pain is a less common symptom complained by CMT patients. We described
      a case of a 39-year-old male patient affect by Charcot-Marie-Tooth (CMT) disease
      compared to five healthy controls (HC), to assess the sensory and the nociceptive
      pathways by using LEPs recording associated to fMRI examination, to find an
      "objective" marker which could be used in the management of CMT patient. The
      nociceptive system was evaluated by laser-evoked potentials (LEPs). Moreover,
      fMRI (functional magnetic resonance imaging) examination, by using laser stimuli,
      was performed. LEPs' examination showed an increase of latency and an amplitude
      reduction respect to HC. The laser stimulation during fMRI showed a decreased
      cortical activations if compared to HC. The originality of this paper, although
      limited to a single case, resides in a detailed evaluation of CMT1 patient
      performed by using neurophysiologic and neuroimaging methods to investigate
      extensively the sensory nociceptive pathways.

PMID- 29644579
TI  - Comparison of Data on Serious Adverse Events and Mortality in ClinicalTrials.gov,
      Corresponding Journal Articles, and FDA Medical Reviews: Cross-Sectional
      Analysis.
AB  - INTRODUCTION: Inconsistencies in data on serious adverse events (SAEs) and
      mortality in ClinicalTrials.gov and corresponding journal articles pose a
      challenge to research transparency. OBJECTIVE: The objective of this study was to
      compare data on SAEs and mortality from clinical trials reported in
      ClinicalTrials.gov and corresponding journal articles with US Food and Drug
      Administration (FDA) medical reviews. METHODS: We conducted a cross-sectional
      study of a randomly selected sample of new molecular entities approved during the
      study period 1 January 2013 to 31 December 2015. We extracted data on SAEs and
      mortality from 15 pivotal trials from ClinicalTrials.gov and corresponding
      journal articles (the two index resources), and FDA medical reviews (reference
      standard). We estimated the magnitude of deviations in rates of SAEs and
      mortality between the index resources and the reference standard. RESULTS: We
      found deviations in rates of SAEs (30% in ClinicalTrials.gov and 30% in
      corresponding journal articles) and mortality (72% in ClinicalTrials.gov and 53%
      in corresponding journal articles) when compared with the reference standard. The
      intra-class correlation coefficient between the three resources was 0.99 (95%
      confidence interval [CI] 0.98-0.99) for SAE rates and 0.99 (95% CI 0.97-0.99) for
      mortality rates. CONCLUSION: There are differences in data on rates of SAEs and
      mortality in randomized clinical trials in both ClinicalTrials.gov and journal
      articles compared with FDA reviews. Further efforts should focus on decreasing
      existing discrepancies to enhance the transparency and reproducibility of data
      reporting in clinical trials.

PMID- 29644580
TI  - On the Efficacy of Cardio-Pulmonary Resuscitation and Epinephrine Following
      Cyanide- and H2S Intoxication-Induced Cardiac Asystole.
AB  - This study was aimed at determining the efficacy of epinephrine, followed by
      chest compressions, in producing a return of spontaneous circulation (ROSC)
      during cyanide (CN)- or hydrogen sulfide (H2S)-induced toxic cardiac pulseless
      electrical activity (PEA) in the rat. Thirty-nine anesthetized rats were exposed
      to either intravenous KCN (n = 27) or H2S solutions (n = 12), at a rate that led
      to a PEA within less than 10 min. In the group intoxicated by CN, 20 rats were
      mechanically ventilated and received either epinephrine (0.1 mg/kg i.v. n = 10)
      followed by chest compressions or saline (n = 10, "control CN") when in PEA. PEA
      was defined as a systolic pressure below 20 mmHg and a pulse pressure of less
      than 5 mmHg for 1 min. In addition, seven spontaneously breathing rats were also
      exposed to the same CN protocol, but infusion was stopped when a central apnea
      occurred; then, as soon as a PEA occurred, epinephrine (0.1 mg/kg IV) was
      administered while providing manual chest compressions and mechanical ventilation
      (CPR). Finally, 12 rats were intoxicated with H2S, while mechanically ventilated,
      and received either saline (n = 6, "control H2S") or epinephrine (n = 6) with CPR
      when in PEA. None of the control-intoxicated animals resuscitated (10 rats in the
      control CN group and 6 in the control H2S group). In contrast, all the animals
      intoxicated with CN or H2S that received epinephrine followed by chest
      compressions, returned to effective circulation. In addition, half of the
      spontaneously breathing CN-intoxicated animals that achieved ROSC after
      epinephrine resumed spontaneous breathing. In all the animals achieving ROSC,
      blood pressure, cardiac output, peripheral blood flow and [Formula: see text]O2
      returned toward baseline, but remained lower than the pre-intoxication levels (p
      < 0.01) with a persistent lactic acidosis. Epinephrine, along with CPR maneuvers,
      was highly effective in resuscitating rodents intoxicated with CN or H2S. Since
      epinephrine is readily available in any ambulance, its place as an important
      countermeasure against mitochondrial poisons should be advocated. It remains
      critical to determine whether the systematic administration of epinephrine to any
      victims found hypotensive following CN or H2S intoxication could prevent PEA,
      decrease post-ischemic brain injury and increase the efficacy of current
      antidotes by improving the circulatory status.

PMID- 29644581
TI  - Exploring Health Beliefs Among Hispanic Adults with Prediabetes.
AB  - Diabetes and prediabetes are increasing in prevalence, corresponding to epidemic
      rates of obesity. Hispanic adults with prediabetes are 1.7 times more likely than
      non-Hispanic whites to progress to diabetes. We set out to understand health
      beliefs of Hispanic adults and, with that knowledge, facilitate tailored
      messaging to promote patient activation and lifestyle change. Using the Risk
      Perception Survey for Developing Diabetes along with demographic and lifestyle
      intervention interest questions, a 34-question survey was mailed to a registry of
      Hispanic adults with a diagnosis of prediabetes and an HbA1c between 5.7 and 6.4%
      (N = 414). Despite more than three-quarters of respondents (n = 92; 77%)
      indicating they had prior knowledge of their diagnosis, overall diabetes risk
      knowledge was low. A significant difference in diabetes risk knowledge was found
      between groups stratified by education level. High scores in personal control and
      worry were reported. Respondents overwhelmingly reported interest in exercise (n
      = 92; 77%) and healthy eating interventions (n = 60; 50%) over technology-based
      interventions. High levels of worry and personal control, combined with low to
      intermediate levels of risk knowledge, indicate an opportunity for education and
      activation in this community. Healthy eating and exercise programs are possible
      interventions that may slow the progression from prediabetes to diabetes.

PMID- 29644582
TI  - A Randomized Placebo-Controlled Cross-Over Pilot Study of Riluzole for Drug
      Refractory Irritability in Autism Spectrum Disorder.
AB  - Riluzole is a glutamatergic modulator of particular interest in autism spectrum
      disorder (ASD). In this 12-week randomized, double-blind, placebo-controlled,
      crossover pilot study we evaluated the safety and tolerability of 5-week of
      adjunctive riluzole treatment (vs. 5-week of placebo, with 2-week washout period)
      targeting ASD-associated drug-refractory irritability in eight individuals age 12
      25 years. All participants tolerated riluzole 200 mg per day, however there were
      no statistically significant findings for the overall treatment effect, the
      treatment effect by week within period of the study, or a cross-over effect
      across the periods of the study on the Clinical Global Impression Improvement
      Scale or the Aberrant Behavior Checklist Irritability subscale. The results of
      this trial indicate that 5-week of riluzole treatment was well tolerated, but had
      no significant effect on the target symptoms. Trial Registration
      ClinicalTrials.gov Identifier NCT02081027, Registered 5 August 2013, First
      participant enrolled 19 September 2013.

PMID- 29644583
TI  - Construction of Past and Future Events in Children and Adolescents with ASD: Role
      of Self-relatedness and Relevance to Decision-Making.
AB  - We studied episodic memory and future thinking for self-relevant and other
      relevant events at different levels of retrieval support, theory of mind, and
      delay discounting in ASD children and adolescents (ASDs). Compared to typically
      developing controls, ASDs produced fewer internal (episodic) but a similar number
      of external (semantic) details while remembering past events, imagining future
      events, and imagining future events happening to others, indicating a general
      impairment of event construction. This deficit was driven by group differences
      under high retrieval support, and therefore unlikely to depend on self-initiated
      retrieval/construction deficits. ASDs' event construction impairment related to
      the severity of ASD symptoms, and to theory of mind deficits. ASDs, however,
      showed normal delay discounting, highlighting preserved forms of future-based
      decision-making in ASD.

PMID- 29644584
TI  - Cost-Effectiveness of Universal or High-Risk Screening Compared to Surveillance
      Monitoring in Autism Spectrum Disorder.
AB  - The American Academy of Pediatrics recommends universal screening for autism
      spectrum disorder at 18 and 24 months. This study compared the cost-effectiveness
      of universal or high-risk screening to surveillance monitoring. Simulation models
      estimated the costs and outcomes from birth to age 6 years. The incremental cost
      per child diagnosed by 36 months was $41,651.6 for high-risk screening and
      $757,116.9 for universal screening from the societal perspective. Universal
      screening may not be a cost-effective approach to increase earlier treatment
      initiation, as most children initiated treatment after age 60 months. Eliminating
      wait times resulted in more children initiated treatment by 48 months, but at a
      high initial cost that may be offset by future cost-savings related to better
      outcomes.

PMID- 29644585
TI  - Non-reciprocal Friendships in a School-Age Boy with Autism: The Ties that Build?
AB  - This mixed-methods study examined differences in social interaction patterns
      between a school-age boy with autism and his friends, non-reciprocal friends, and
      non-friends during recess time at a mainstream school (third grade of elementary
      school). Through a combination of observational methodology and social network
      analysis with an idiographic, follow-up and multidimensional design approach, we
      used lag sequential and polar coordinate analysis to ascertain the associations
      between various interactive behaviors as a function of type of friendship
      relation. After 40 sessions, we found that the non-reciprocal friendship
      relations of the boy with autism could have significantly greater potential than
      his reciprocal friendships to increase active engagement and reduce the time he
      spent alone during recess.

PMID- 29644586
TI  - Brief Report: Autism Spectrum Disorder: A Comprehensive Survey of Randomized
      Controlled Trials.
AB  - We searched the Cochrane Central Register of Controlled Trials to provide an
      overview of evidence from randomized controlled trials (RCTs) of therapeutic
      interventions for autism spectrum disorders. From the final survey (529 RCTs),
      the mean size was 49 participants (standard deviation 50, range 1-479, median 36,
      mode 40), with a sharp increase in the number of RCTs from 2008. The most
      frequently evaluated intervention was antipsychotic treatment (n = 44, 3006
      participants). The journal with the most RCTs was the Journal of Autism and
      Developmental Disorders (N = 104). Most trials were small in size, emphasising
      the need for research groups to collaborate to generate higher quality data with
      greater applicability to clinical practice.

PMID- 29644592
TI  - Keyword Index to Volume 28.

PMID- 29644587
TI  - The Feeling of Me Feeling for You: Interoception, Alexithymia and Empathy in
      Autism.
AB  - Following recent evidence for a link between interoception, emotion and empathy,
      we investigated relationships between these factors in autism spectrum disorder
      (ASD). 26 adults with ASD and 26 healthy participants completed tasks measuring
      interoception, alexithymia and empathy. ASD participants with alexithymia
      demonstrated lower cognitive and affective empathy than ASD participants without
      alexithymia. ASD participants showed reduced interoceptive sensitivity (IS), and
      also reduced interoceptive awareness (IA). IA was correlated with empathy and
      alexithymia, but IS was related to neither. Alexithymia fulfilled a mediating
      role between IA and empathy. Our findings are suggestive of an alexithymic
      subgroup in ASD, with distinct interoceptive processing abilities, and have
      implications for diagnosis and interventions.

PMID- 29644588
TI  - Meta-analysis of Tablet-Mediated Interventions for Teaching Academic Skills to
      Individuals with Autism.
AB  - Portable touch-screen devices have been the focus of a notable amount of
      intervention research involving individuals with autism. Additionally, popular
      media has widely circulated claims that such devices and academic software
      applications offer tremendous educational benefits. A systematic search
      identified 19 studies that targeted academic skills for individuals with autism.
      Most studies used the device's built-in video recording or camera function to
      create customized teaching materials, rather than commercially-available
      applications. Analysis of potential moderating variables indicated that
      participants' age and functioning level did not influence outcomes. However,
      participant operation of the device, as opposed to operation by an instructor,
      produced significantly larger effect size estimates. Results are discussed in
      terms of recommendations for practitioners and future research.

PMID- 29644593
TI  - Valorization of the Crude Glycerol for Propionic Acid Production Using an
      Anaerobic Fluidized Bed Reactor with Grounded Tires as Support Material.
AB  - This study evaluated the propionic acid (HPr) production from crude glycerol (CG)
      (5000 mg L-1) in an anaerobic fluidized bed reactor (AFBR). Grounded tire
      particles (2.8-3.35 mm) were used as support material for microbial adhesion. The
      reactor was operated with hydraulic retention times (HRT) varying from 8 to 0.5 h
      under mesophilic (30  degrees C) conditions. The HPr was the main metabolite
      produced, increasing in composition from 66.5 to 99.6% by decreasing the HRT from
      8 to 0.5 h. Other metabolic products were 1,3-propanediol, with a maximum of
      29.4% with an HRT of 6 h, ethanol, acetic, and butyric acids. The decrease in HRT
      from 8 to 0.5 h decreased the HPr yield, with a maximum of 0.48 +/- 0.06 g HPr g
      COD-1 and an HRT of 6 h, and favored HPr productivity, with a maximum of 4.09 +/-
      1.24 g L-1 h-1 and HRT of 0.5 h. In the biogas, the H2 content increased from
      12.5 to 81.2% by decreasing the HRT from 8 to 0.5 h. These results indicate the
      potential application of the AFBR for HPr production using an immobilized mixed
      culture.

PMID- 29644594
TI  - Hydrothermal Carbonization of Microalgae (Chlorococcum sp.) for Porous Carbons
      With High Cr(VI) Adsorption Performance.
AB  - Porous carbon adsorbents were prepared from microalgae (Chlorococcum sp.) via
      directly hydrothermal carbonization coupled with KOH or NH3 activation for Cr(VI)
      adsorption. KOH-activated porous carbons exhibit high Cr(VI) adsorption
      capacities than those obtained via NH3 modification (370.37 > 95.70 mg/g). The
      superior Cr(VI) adsorption capacity is due to high surface areas (1784 m2/g) and
      pore volumes of porous carbon with mesoporous and macroporous structures. The
      Cr(VI) adsorption result was well fitted to the Langmuir model, showing that the
      removal of Cr(VI) was attributed to the monolayer adsorption of activity site on
      carbon surface.

PMID- 29644595
TI  - Enhanced Bioethanol Production from Potato Peel Waste Via Consolidated
      Bioprocessing with Statistically Optimized Medium.
AB  - In this study, an extensive screening was undertaken to isolate some amylolytic
      microorganisms capable of producing bioethanol from starchy biomass through
      Consolidated Bioprocessing (CBP). A total of 28 amylolytic microorganisms were
      isolated, from which 5 isolates were selected based on high alpha-amylase and
      glucoamylase activities and identified as Candida wangnamkhiaoensis, Hyphopichia
      pseudoburtonii (2 isolates), Wickerhamia sp., and Streptomyces drozdowiczii based
      on 26S rDNA and 16S rDNA sequencing. Wickerhamia sp. showed the highest ethanol
      production (30.4 g/L) with fermentation yield of 0.3 g ethanol/g starch. Then, a
      low cost starchy waste, potato peel waste (PPW) was used as a carbon source to
      produce ethanol by Wickerhamia sp. Finally, in order to obtain maximum ethanol
      production from PPW, a fermentation medium was statistically designed. The effect
      of various medium ingredients was evaluated initially by Plackett-Burman design
      (PBD), where malt extracts, tryptone, and KH2PO4 showed significantly positive
      effect (p value < 0.05). Using Response Surface Modeling (RSM), 40 g/L (dry
      basis) PPW and 25 g/L malt extract were found optimum and yielded 21.7 g/L
      ethanol. This study strongly suggests Wickerhamia sp. as a promising candidate
      for bioethanol production from starchy biomass, in particular, PPW through CBP.

PMID- 29644596
TI  - Nanofibrous Tubular Membrane for Blood Hemodialysis.
AB  - As the most important components of a hemodialysis device, nanofibrous membranes
      enjoy high interconnected porosity and specific surface area as well as excellect
      permeability. In this study, a tubular nanofibrous membrane of polysulfone
      nanofibers was produced via electrospinning method to remove urea and creatinine
      from urine and blood serums of dialysis patients. Nanofibrous membranes were
      electrospun at a concentration of 11.5 wt% of polysulfone (PS) and
      dimethylformamide (DMF)/tetrahydrofuran (THF) with a ratio of 70/30. The effects
      of the rotational speed of collectors, electrospinning duration, and inner
      diameter of the tubular nanofibrous membrane on the urea and creatinine removal
      efficiency of the tubular membrane were investigated through the hemodialysis
      simulation experiments. It was found that the tubular membrane with an inner
      diameter of 3 mm elecrospun at shorter duration with lower collecting speed had
      the highest urea and creatinine removal efficiency. The hemodialysis simulation
      experiment showed that the urea and creatinine removal efficiency of the tubular
      membrane with a diameter of 3 mm were 90.4 and 100%, respectively. Also, three
      patients' blood serums were tested with the nanofibrous membrane. The results
      showed that the creatinine and urea removal rates were 93.2 and 90.3%,
      respectively.

PMID- 29644597
TI  - Plant-borne compounds and nanoparticles: challenges for medicine, parasitology
      and entomology.

PMID- 29644598
TI  - Essential Roles of Lactate in Muller Cell Survival and Function.
AB  - Muller cells are pivotal in sustaining retinal ganglion cells, and an intact
      energy metabolism is essential for upholding Muller cell functions. The present
      study aimed to investigate the impact of lactate on Muller cell survival and
      function. Primary mice Muller cells and human Muller cell lines (MIO-M1) were
      treated with or without lactate (10 or 20 mM) for 2 and 24 hours. Simultaneously,
      Muller cells were incubated with or without 6 mM of glucose. L-lactate exposure
      increased Muller cell survival independently of the presence of glucose. This
      effect was abolished by the addition of the monocarboxylate inhibitor 4-cinnamic
      acid to the treatment media, whereas survival continued to increase in response
      to addition of D-lactate during glucose restriction. ATP levels decreased over
      time in MIO-M1 cells and remained stable over time in primary Muller cells.
      Lactate was preferably metabolized in MIO-M1 cells compared to glucose, and 10 mM
      of L-Lactate exposure prevented complete glycogen depletion in MIO-M1 cells.
      Glutamate uptake increased after 2 hours and decreased after 24 hours in glucose
      restricted Muller cells compared to cells with glucose supplement. The addition
      of 10 mM of lactate to the treatment media increased glutamate uptake in glucose
      supplemented and restricted cells. In conclusion, lactate is a key component in
      maintaining Muller cell survival and function. Hence, lactate administration may
      be of great future interest, ultimately leading to novel therapies to rescue
      retinal ganglion cells.

PMID- 29644599
TI  - Long-term effectiveness and safety of metreleptin in the treatment of patients
      with generalized lipodystrophy.
AB  - PURPOSE: The purpose of this study is to summarize the effectiveness and safety
      of metreleptin in patients with congenital or acquired generalized lipodystrophy.
      METHODS: Patients (n = 66) aged >=6 months had lipodystrophy, low circulating
      leptin, and >=1 metabolic abnormality (diabetes mellitus, insulin resistance, or
      hypertriglyceridemia). Metreleptin dose (once or twice daily) was titrated to a
      mean dose of 0.10 mg/kg/day with a maximum of 0.24 mg/kg/day. Means and changes
      from baseline to month 12 were assessed for glycated hemoglobin (HbA1c), fasting
      triglycerides (TGs), and fasting plasma glucose (FPG). Additional assessments
      included the proportions of patients achieving target decreases in HbA1c or
      fasting TGs at months 4, 12, and 36, medication changes, and estimates of liver
      size. Treatment-emergent adverse events (TEAEs) were recorded. RESULTS:
      Significant mean reductions from baseline were seen at month 12 for HbA1c (-2.2%,
      n = 59) and FPG (-3.0 mmol/L, n = 59) and mean percent change in fasting TGs (
      32.1%, n = 57) (all p <= 0.001). Reductions from baseline over time in these
      parameters were also significant at month 36 (all p < 0.001, n = 14). At month 4,
      34.8% of patients had a >=1% reduction in HbA1c and 62.5% had a >=30% reduction
      in fasting TGs; at month 12, 80% of patients had a >=1% decrease in HbA1c or
      >=30% decrease in TGs, and 66% had a decrease of >=2% in HbA1c or >=40% decrease
      in TGs. Of those on medications, 41%, 22%, and 24% discontinued insulin, oral
      antidiabetic medications, or lipid-lowering medications, respectively. Mean
      decrease in liver volume at month 12 was 33.8% (p < 0.001, n = 12). Most TEAEs
      were of mild/moderate severity. CONCLUSIONS: In patients with generalized
      lipodystrophy, long-term treatment with metreleptin was well tolerated and
      resulted in sustained improvements in hypertriglyceridemia, glycemic control, and
      liver volume.

PMID- 29644601
TI  - The Michigan Bright Nights Community Forum Series: a 10-Year Experience with
      Public Mental Health Education.

PMID- 29644600
TI  - Schwann-Cell Autophagy, Functional Recovery, and Scar Reduction After Peripheral
      Nerve Repair.
AB  - The functional outcome after peripheral nerve repair is often unpredictable for
      many reasons, e.g., the severity of neuronal death and scarring. Axonal
      degeneration significantly affects outcomes. Post-injury axonal degeneration in
      peripheral nerves is accompanied by myelin degradation initiated by Schwann cells
      (SCs), which activate autophagy, a ubiquitous cytoprotective process essential
      for degrading and recycling cellular constituents. Scar formation occurs
      concomitantly with nerve insult and axonal degeneration. The association between
      SC autophagy and the mechanisms of nerve scar formation is still unknown. A rat
      model of peripheral nerve lesions induced by sciatic nerve transection injuries
      was used to examine the function of autophagy in fibrosis reduction during the
      early phase of nerve repair. Rats were treated with rapamycin (autophagy inducer)
      or 3-methyladenine (autophagy inhibitor). One week after the nerve damage,
      fibrosis was potently inhibited in rapamycin-treated rats and, based on gait
      analysis, yielded a better functional outcome. Immunohistochemistry showed that
      the autophagic activity of SCs and the accumulation of neurofilaments were
      upregulated in rapamycin-treated rats. A deficiency of SC autophagic activity
      might be an early event in nerve scar formation, and modulating autophagy might
      be a powerful pharmacological approach for improving functional outcomes.

PMID- 29644602
TI  - Work Related Post Traumatic Stress Disorder in Medicine Residents.
AB  - OBJECTIVE: This study sought to screen for the burden of work-related
      posttraumatic stress disorder (PTSD) symptoms in internal medicine residents.
      METHODS: A cross-sectional survey of internal medicine residents from three
      academic institutions was conducted using the PCL-5 screening tool. RESULTS: Off
      all residents surveyed, 5.2% screened positive for PTSD symptoms (N = 194). 86.1%
      of all trainees identified stressors during training. Positive PTSD screens were
      significantly higher in PGY3 residents (X2 = 15.24, p = 0.0005). Of all PGY3
      residents, 9.8% (N = 4) and 14.6% (N = 6) of residents screened positive for PTSD
      symptoms based on absolute and cluster score criteria, respectively.
      Verbal/physical assault by patients/families/colleagues were triggers for the
      most cases of positive screens. CONCLUSIONS: Self-reported stressors are highly
      prevalent in internal medicine trainees. Verbal/physical assault by patients and
      families appear to be the triggering event for most positive screens. These
      observations will help with future study designs to quantify the burden of work
      related PTSD in internal medicine trainee physicians so that appropriate
      supportive measures can be provided.

PMID- 29644603
TI  - Assessment of intake of copper and lead by sheep grazing on a shooting range for
      small arms: a case study.
AB  - The Norwegian Armed Forces' shooting ranges contain contamination by metals such
      as lead (Pb) and copper (Cu) and are often used as grazing pastures for
      livestock. To determine whether the sheep were at risk from grazing at a shooting
      range in Nord-Trondelag (the Leksdalen shooting field), a study was conducted
      wherein the aim was to determine the amount of soil the sheep were eating, the
      accumulation of Cu and Pb in the livers of lambs grazing on the shooting ranges,
      and the accumulation of Pb and Cu in the grass. The grazing behavior of the sheep
      was mapped using GPS tracking and wildlife cameras. Soil, grass, feces, and liver
      samples were collected. All the samples were analyzed for Pb, Cu, and molybdenum
      (Mo), and soil and feces were also analyzed for titanium (Ti). Mean
      concentrations in grass, soil, feces, and liver was 41-7189, 1.3-29, 4-5, and 0.3
      mg/kg Pb, respectively, and 42-580, 4.2-11.9, 19-23, and 273 mg/kg Cu,
      respectively. The soil ingestion rate was calculated using Ti in feces and soil.
      From these results, the theoretical dose of Cu and Pb ingested by grazing sheep
      was calculated. The soil ingestion rate was found to be 0.1-0.4%, significantly
      lower than the soil ingestion rate of 5-30% usually used for sheep. Little or no
      accumulation of Cu and Pb in the grass was found. There was no difference between
      the metal concentrations in the washed and unwashed grass. According to the
      calculated dose, the sheep were at little or no risk of acute or chronic Pb and
      Cu poisoning from grazing on the Leksdalen shooting range. The analysis of liver
      samples showed that lambs grazing on the shooting range did not have higher
      levels of Cu or Pb than lambs grazing elsewhere. None of the lambs had
      concentrations of Cu or Pb in their livers indicating poisoning.

PMID- 29644604
TI  - Groundwater nitrate pollution and climate change: learnings from a water balance
      based analysis of several aquifers in a western Mediterranean region (Catalonia).
AB  - Climate change will affect the dynamics of the hydrogeological systems and their
      water resources quality; in particular nitrate, which is herein taken as a
      paradigmatic pollutant to illustrate the effects of climate change on groundwater
      quality. Based on climatic predictions of temperature and precipitation for the
      horizon of 2021 and 2050, as well as on land use distribution, water balances are
      recalculated for the hydrological basins of distinct aquifer systems in a western
      Mediterranean region as Catalonia (NE Spain) in order to determine the reduction
      of available water resources. Besides the fact that climate change will represent
      a decrease of water availability, we qualitatively discuss the modifications that
      will result from the future climatic scenarios and their impact on nitrate
      pollution according to the geological setting of the selected aquifers. Climate
      effects in groundwater quality are described according to hydrological,
      environmental, socio-economic, and political concerns. Water reduction stands as
      a major issue that will control stream-aquifer interactions and subsurface
      recharge, leading to a general modification of nitrate in groundwater as dilution
      varies. A nitrate mass balance model provides a gross estimation of potential
      nitrate evolution in these aquifers, and it points out that the control of the
      fertilizer load will be crucial to achieve adequate nitrate content in
      groundwater. Reclaimed wastewater stands as local reliable resource, yet its
      amount will only satisfy a fraction of the loss of available resources due to
      climate change. Finally, an integrated management perspective is necessary to
      avoid unplanned actions from private initiatives that will jeopardize the
      achievement of sustainable water resources exploitation under distinct
      hydrological scenarios.

PMID- 29644605
TI  - A new marine sediment certified reference material (CRM) for the determination of
      persistent organic contaminants: IAEA-459.
AB  - A new marine sediment certified reference material (IAEA 459) with very low
      concentrations (MUg kg-1) for a variety of persistent organic contaminants (POPs)
      listed by the Stockholm Convention, as well as other POPs and priority substances
      (PSs) listed in many environmental monitoring programs was developed by the IAEA.
      The sediment material was collected from the Ham River estuary in South Korea,
      and the assigned final values were derived from robust statistics on the results
      provided by selected laboratories which demonstrated technical and quality
      competence, following the guidance given in ISO Guide 35. The robust mean of the
      laboratory means was assigned as certified values, for those compounds where the
      assigned value was derived from at least five datasets and its relative expanded
      uncertainty was less than 40% of the assigned value (most of the values ranging
      from 8 to 20%). All the datasets were derived from at least two different
      analytical techniques which have allowed the assignment of certified
      concentrations for 22 polychlorinated biphenyl (PCB) congeners, 6
      organochlorinated (OC) pesticides, 5 polybrominated diphenyl ethers (PBDEs), and
      18 polycyclic aromatic hydrocarbon (PAHs). Mass fractions of compounds that did
      not fulfill the criteria of certification are considered information values,
      which include 29 PAHs, 11 PCBs, 16 OC pesticides, and 5 PBDEs. The extensive
      characterization and associated uncertainties at concentration levels close to
      the marine sediment quality guidelines will make CRM 459 a valuable matrix
      reference material for use in marine environmental monitoring programs.

PMID- 29644606
TI  - River habitat assessment for ecological restoration of Wei River Basin, China.
AB  - As an important composition component of river ecosystems, river habitats must
      undergo quality assessment to potentially provide scientific basis for river
      ecological restoration. Substrate composition, habitat complexity, bank erosion
      degree, river meandering degree, human activity intensity, vegetation buffer
      width, water quality, and water condition were determined as indicators for river
      habitat assessment. The comprehensive habitat quality index (CHQI) was
      established for the Wei River Basin. In addition, the indicator values were
      determined on the basis of a field investigation at 12 national hydrological
      stations distributed across the Wei, Jing, and Beiluo Rivers. The analytic
      hierarchy process was used to determine the indicator weights and thus
      distinguish the relative importance of the assessment indicator system. Results
      indicated that the average CHQIs for the Wei, Jing, and Beiluo Rivers were 0.417,
      0.508, and 0.304, respectively. The river habitat quality for the three rivers
      was well. As for the whole river basin, the river habitat quality for 25% of the
      cross section was very well, the other 25% was well, and the 50% remaining was in
      critical state. The river habitat quality of the Jing River was better than that
      of the Wei and Beiluo Rivers.

PMID- 29644607
TI  - Thermal effects from the release of selenium from a coal combustion during high
      temperature processing: a review.
AB  - The release of selenium (Se) during coal combustion can have serious impacts on
      the ecological environment and human health. Therefore, it is very important to
      study the factors that concern the release of Se from coal combustion. In this
      paper, the characteristics of the release of Se from coal combustion, pyrolysis,
      and gasification of different coal species under different conditions are
      studied. The results show that the amount of released Se increases at higher
      combustion temperatures. There are obvious increases in the amount of released Se
      especially in the temperature range of 300 to 800  degrees C. In addition, more
      Se is released from the coal gasification than coal combustion process, but more
      Se is released from coal combustion than pyrolysis. The type of coal, rate of
      heating, type of mineral ions, and combustion atmosphere have different effects
      on the released percentage of Se. Therefore, having a good understanding of the
      factors that surround the release of Se during coal combustion, and then
      establishing the combustion conditions can reduce the impacts of this toxic
      element to humans and the environment.

PMID- 29644608
TI  - Reclamation of a lignite combustion waste disposal site with alders (Alnus sp.):
      assessment of tree growth and nutrient status within 10 years of the experiment.
AB  - Combustion wastes are characterised by extremely low N contents. Therefore,
      introduction of nitrogen-fixing species at the first stage of their biological
      reclamation is required. This paper presents an assessment of the growth
      parameters of alders (Alnus sp.) 10 years after their introduction to a disposal
      site of lignite combustion waste in Central Poland. Black (Alnus glutinosa) and
      grey alders (Alnus incana) were planted directly in the combustion waste. The
      soil amendment included three variants: control with pure combustion waste,
      admixture of lignite culm and addition of acid sand. Both alder species displayed
      good growth parameters comparable to those of alders in natural habitats.
      However, black alder had better growth parameters, such as stand density index
      (SDI), diameter at breast height (DBH) and height (H) than grey alder. The
      lignite amendment exerted a positive effect on tree growth, reflected in a higher
      SDI and H, whereas the acid sand amendment did not affect any of the growth
      parameters of the studied alder species. Despite the good growth parameters, the
      measured N:P and N:K ratios in the alder leaves largely differed from the optimal
      values indicating insufficient P and K supply at the combustion waste disposal
      site. This may pose a threat to further development of the introduced tree
      plantings. The introduction of alders along with the lignite addition into the
      planting holes seems to be a successful method of combustion waste revegetation.

PMID- 29644609
TI  - Mercury species accumulation and distribution in Typha domingensis under real
      field conditions (Almaden, Spain).
AB  - Monomethylmercury (MeHg) is one of the most toxic and the most commonly occurring
      organomercury compound and the wetlands are one of the main areas of generation
      of this Hg form. Concretely, it is in the macrophyte root system where better
      conditions are given for its generation. However, the knowledge of absorption and
      subsequent distribution of mercury (Hg) and monomethylmercury in aquatic plants
      is still limited. Mercury mining district such as Almaden (Ciudad Real, Spain) is
      a natural laboratory where different rivers flow and the species Typha
      domingensis Pers. is a common macrophyte which grows in their riverbanks. The aim
      of the present work is to apply a recently developed method specially designed to
      analyze Hg species in plant tissues to the different fractions of T. domingensis
      under real field conditions and to study the accumulation and distribution of Hg
      species (inorganic Hg and MeHg) within the plant. The results proved that
      whatever Hg species has preference to be accumulated in the belowground fractions
      and demonstrated a high efficiency in the accumulation of MeHg.

PMID- 29644610
TI  - X-ray fluorescence spectrometry characteristics of oily waste water from steel
      processing and an evaluation of its impact on the environment.
AB  - Metal-cutting fluids, one of the most consumed materials in the metallurgy
      industry, turn into oily wastewater after being used in the metalworking
      processes. The amount of cutting fluids used can reach up to millions of tons.
      And these invaluable fluids are difficult to distil and expensive, and impossible
      to store. Even after it is disposed and recaptured, the end product has no
      commercial value. In this study, the effect of this mixture was examined on the
      ecosystem using the Allium cepa test system in which onion root tips were treated
      with three different concentrations of waste-cutting fluid, based on a 24- and 48
      h cell cycle. The oily wastewater exhibited a mechanism which triggered the
      chromosomal and nuclear abnormalities in the onion root-tip meristem and reduced
      the mitotic index. Common abnormalities observed in the experimental groups based
      on the water concentration were chromosome stickiness, c-mitosis, and micronuclei
      formation. In the experimental group with the lowest water concentration, budding
      nuclei were observed at a different level than all of the other experimental
      groups. The x-ray fluorescence analysis showed that the concentrations of
      elements, such as silicon, calcium, iron, and zinc, were higher in the oily
      wastewater than those in the unused cutting oil.

PMID- 29644611
TI  - Atmospheric fossil fuel CO2 traced by 14CO2 and air quality index pollutant
      observations in Beijing and Xiamen, China.
AB  - Radiocarbon (14C) is the most accurate tracer available for quantifying
      atmospheric CO2 derived from fossil fuel (CO2ff), but it is expensive and time
      consuming to measure. Here, we used common hourly Air Quality Index (AQI)
      pollutants (AQI, PM2.5, PM10, and CO) to indirectly trace diurnal CO2ff
      variations during certain days at the urban sites in Beijing and Xiamen, China,
      based on linear relationships between AQI pollutants and CO2ff traced by 14C
      ([Formula: see text]) for semimonthly samples obtained in 2014. We validated
      these indirectly traced CO2ff (CO2ff-in) concentrations against [Formula: see
      text] concentrations traced by simultaneous diurnal 14CO2 observations.
      Significant (p < 0.05) strong correlations were observed between each of the
      separate AQI pollutants and [Formula: see text] for the semimonthly samples.
      Diurnal variations in CO2ff traced by each of the AQI pollutants generally showed
      similar trends to those of [Formula: see text], with high agreement at the
      sampling site in Beijing and relatively poor agreement at the sampling site in
      Xiamen. AQI pollutant tracers showed high normalized root-mean-square (NRMS)
      errors for the summer diurnal samples due to low [Formula: see text]
      concentrations. After the removal of these summer samples, the NRMS errors for
      AQI pollutant tracers were in the range of 31.6-64.2%. CO generally showed a high
      agreement and low NRMS errors among these indirect tracers. Based on these linear
      relationships, monthly CO2ff averages at the sampling sites in Beijing and Xiamen
      were traced using CO concentration as a tracer. The monthly CO2ff averages at the
      Beijing site showed a shallow U-type variation. These results indicate that CO
      can be used to trace CO2ff variations in Chinese cities with CO2ff concentrations
      above 5 ppm.

PMID- 29644612
TI  - Tissue distribution and oral exposure risk assessment of heavy metals in an urban
      bird: magpie from Central Iran.
AB  - Direct ingestion of soil and/or soil attached to the food items is a potential
      rout for wildlife exposure to contaminants. In this study, bioaccumulation of
      five heavy metals (HMs) in internal tissues of an urban bird (Pica pica)
      collected from Aran-O-Bidgol City, Central Iran and their related soil were
      investigated. A total of 15 magpie specimens were collected in autumn 2013 and
      then their internal tissues were digested using a mixture of HNO3 and H2O2, and
      finally, concentrations of HMs were detected by ICP-OES. In addition, in order to
      show level of HM exposure risk to magpie, an exposure risk assessment was
      modeled. Results indicated that HMs were accumulated as follows: liver > kidney >
      muscle. Zn and Cu were significantly higher in magpie's tissues collected from
      agricultural site; on the other hand, Pb and Cd were significantly higher in
      industrial site (p < 0.05). Level of Cd in male's livers (2.11 MUg/g dw) was
      significantly higher than in females (1.85 MUg/g dw) (p < 0.05). Levels of Cd,
      Pb, and Ni in liver, muscle, and kidney, respectively, were significantly higher
      in adults than in subadults (p < 0.05). Soil exposure doses of all HMs were lower
      than tolerable daily intake (Zn 4.35, Cu 1.34, Ni 5.65, Pb 0.35, and Cd 0.53).
      The calculated hazard quotations (HQs) for HMs were as follows: Pb > Zn > Cu > Ni
      > Cd and for all HMs were at no risk level (HQ < 1). The amounts of hazard index
      for three sites were as follows: urban (1.032) > agriculture (0.943) >= industry
      (0.941) and only for urban area was at low risk (1 < HQ < 2). It seemed that
      birds living in a safe environment and/or HM contaminations in soil separately
      had no negative effects on magpies. We can also suggest that low levels of HMs in
      magpie's tissues can be due to low levels of HMs in soil.

PMID- 29644613
TI  - Low-level concentrations of aminoglycoside antibiotics induce the aggregation of
      cyanobacteria.
AB  - The interactions between antibiotics and microorganisms have attracted enormous
      research attentions. In this study, we investigated the effects of two typical
      aminoglycoside antibiotics on the aggregation of the model cyanobacterium,
      Synechococcus elongatus, and the dominating strain in algal blooms, Microcystis
      aeruginosa, via the analysis of zeta potentials, hydrophobicity, and
      extracellular polymeric substances (EPS) secretion. The results showed that low
      level antibiotics promoted the aggregation of S. elongatus and M. aeruginosa by
      40 and 18% under 0.10 and 0.02 MUg/mL of kanamycin, respectively, which was
      mainly attributed to the combined effects of increased zeta potentials and the
      ratio between extracellular proteins and polysaccharides. Tobramycin exerted
      similar effects. Additionally, we discovered that at low pH (pH 5) and ionic
      strength (1 mM Na+ and 2 mM Mg2+), the inducing effects of antibiotics would be
      even larger than those with higher pH and ionic strength. As aggregation is
      important to cyanobacteria in either the basic physiology of biofilm formation or
      the algal bloom, our study demonstrated that low-level antibiotics exert
      ecological impacts via interfered aggregation. We believe this study will shed
      light on the mechanisms underlying antibiotic-induced biofilm formation and help
      with the evaluation of the environmental and ecological risks of antibiotics and
      other emerging pollutants.

PMID- 29644614
TI  - Comparison of pathogen-derived 'total risk' with indicator-based correlations for
      recreational (swimming) exposure.
AB  - Typical recreational water risk to swimmers is assessed using epidemiologically
      derived correlations by means of fecal indicator bacteria (FIB). It has been
      documented that concentrations of FIB do not necessarily correlate well with
      protozoa and viral pathogens, which pose an actual threat of illness and thus
      sometimes may not adequately assess the overall microbial risks from water
      resources. Many of the known pathogens have dose-response relationships; however,
      measuring water quality for all possible pathogens is impossible. In
      consideration of a typical freshwater receiving secondarily treated effluent, we
      investigated the level of consistency between the indicator-derived correlations
      and the sum of risks from six reference pathogens using a quantitative microbial
      risk assessment (QMRA) approach. Enterococci and E. coli were selected as the
      benchmark FIBs, and norovirus, human adenovirus (HAdV), Campylobacter jejuni,
      Salmonella enterica, Cryptosporidium spp., and Giardia spp. were selected as the
      reference pathogens. Microbial decay rates in freshwater and uncertainties in
      exposure relationships were considered in developing our analysis. Based on our
      exploratory assessment, the total risk was found within the range of risk
      estimated by the indicator organisms, with viral pathogens as dominant risk
      agents, followed by protozoan and bacterial pathogens. The risk evaluated in this
      study captured the likelihood of gastrointestinal illnesses only, and did not
      address the overall health risk potential of recreational waters with respect to
      other disease endpoints. Since other highly infectious pathogens like hepatitis A
      and Legionella spp. were not included in our analysis, these estimates should be
      interpreted with caution.

PMID- 29644615
TI  - Assessment of the inhalation risks associated with working in printing rooms: a
      study on the staff of eight printing rooms in Beijing, China.
AB  - The concentration of pollution directly determines the occupational health risk,
      and the exposure time is an important influencing factor. We evaluated the
      inhalation risks of working in a printing room. Eight units with centralized
      printing rooms were randomly selected. Formaldehyde, ozone, benzene, toluene,
      xylene, and fine particulate matter were detected by spectrophotometry, gas
      chromatography, and direct reading instruments, respectively. The U.S. EPA
      inhalation risk assessment model was used to assess cancer and non-cancer risks.
      The formaldehyde inhalation cancer risk value was 1.35-3.45 * 10-6, which is
      greater than the limit of 1 * 10-6, suggesting a risk of squamous cell carcinoma.
      The benzene inhalation cancer risk in five of the rooms was 1.09-4.65 * 10-6,
      which is greater than the limit of 1 * 10-6, suggesting a risk of leukemia. In
      terms of non-cancer risk, in five of the rooms, the hazard quotient (HQ) was > 1
      (range 1.99-4.69) due to benzene pollution, suggesting a risk of reduced
      lymphocyte count. In one room, due to benzene and xylene pollution, the HQ was >
      1, suggesting a risk of lymphocyte count drop and motor coordination impairment.
      Collectively, the study concludes that staff members of printing rooms are
      exposed to both cancer and non-cancer occupational health risks.

PMID- 29644616
TI  - Genetic aberrations of the K-ras proto-oncogene in bladder cancer in relation to
      pesticide exposure.
AB  - In Egypt, bladder cancer is one of the most popular cancers, accounting for 31%
      of all cancer cases. It ranks first in males about 16.2% of male cancer. The
      incidence in rural areas among males is near 32 per 100,000. The exact etiology
      of bladder cancer is still unknown; K-ras gene is known as a critical DNA target
      for chemical carcinogens such as pesticide. Some occupational hazard exposure is
      thought to be directly genotoxic, while others might enhance the mutagenicity and
      carcinogenicity of directly acting genotoxic agents. Analysis of the relationship
      between pesticide exposure and mutation in the K-ras gene in human bladder
      cancer. One hundred patients were diagnosed with bladder cancer and two hundred
      controls attended the outpatient clinic; after taking consent and filling a
      questionnaire for age, sex, occupation and pesticide exposure, surgically
      resected specimens were collected and the samples were used to determine the k
      ras mutation. Blood samples were taken to analyze the level of
      acetylcholinesterase enzyme and level of P53. The present study indicated that
      pesticide exposure may play a great role in malignant transformation of the
      bladder cells through mutation in the K-ras gene; there was a significant
      correlation between the acetylcholinesterase enzyme level and k-ras mutation (p <
      0.001). The results revealed that the level of P53 was significantly high in
      comparison with the control group (p < 0.001). These findings give an alarm to
      decrease the amount of pesticides used in our area; also, p53 may be used as an
      indicator to bladder cancer.

PMID- 29644617
TI  - Study on sandstorm PM10 exposure assessment in the large-scale region: a case
      study in Inner Mongolia.
AB  - The current exposure-effect curves describing sandstorm PM10 exposure and the
      health effects are drawn roughly by the outdoor concentration (OC), which ignored
      the exposure levels of people's practical activity sites. The main objective of
      this work is to develop a novel approach to quantify human PM10 exposure by their
      socio-categorized micro-environment activities-time weighed (SCMEATW) in strong
      sandstorm period, which can be used to assess the exposure profiles in the large
      scale region. Types of people's SCMEATW were obtained by questionnaire
      investigation. Different types of representatives were trackly recorded during
      the big sandstorm. The average exposure levels were estimated by SCMEATW.
      Furthermore, the geographic information system (GIS) technique was taken not only
      to simulate the outdoor concentration spatially but also to create human exposure
      outlines in a visualized map simultaneously, which could help to understand the
      risk to different types of people. Additionally, exposure-response curves
      describing the acute outpatient rate odds by sandstorm were formed by SCMEATW,
      and the differences between SCMEATW and OC were compared. Results indicated that
      acute outpatient rate odds had relationships with PM10 exposure from SCMEATW,
      with a level less than that of OC. Some types of people, such as herdsmen and
      those people walking outdoors during a strong sandstorm, have more risk than
      office men. Our findings provide more understanding of human practical activities
      on their exposure levels; they especially provide a tool to understand sandstorm
      PM10 exposure in large scale spatially, which might help to perform the different
      categories population's risk assessment regionally.

PMID- 29644618
TI  - Adherence to Basal Insulin Therapy Among People with Type 2 Diabetes: A
      Retrospective Cohort Study of Costs and Patient Outcomes.
AB  - INTRODUCTION: This research compares costs, resource utilization, and
      complications between adherent and nonadherent patients over the 3-year period
      post initiation on basal insulin therapy. METHODS: The study utilized the US
      based Truven Health MarketScan(r) Research Databases from 2011 through 2015.
      Adults aged 18 years or older and identified with type 2 diabetes (T2D) who
      initiated therapy on basal insulin in 2012 were included. Patients were excluded
      if they were pregnant, filled their index basal insulin prescription via mail
      order, or were not continuously insured from 1 year before through 3 years
      following initiation of treatment with basal insulin. Instrumental variables were
      used to control for selection bias, and multivariable analyses were used to
      examine the associations between adherence to basal insulin therapy and costs,
      resource utilization, and acute complications. RESULTS: A total of 21,363
      individuals were included in the study. Three years after initiating therapy on
      basal insulin, patients who were adherent over time to basal insulin treatment
      therapy (33.8% of patients) had significantly higher diabetes-related drug costs.
      However, patients' adherence was associated with significantly lower diabetes
      related outpatient, acute care, and total costs. Results for all-cause costs were
      similar. Adherent patients also had significantly fewer all-cause and diabetes
      related hospitalizations and emergency room visits and were significantly less
      likely to be diagnosed with an acute complication. CONCLUSIONS: Results of this
      study illustrate that despite higher drug costs, there are disease-specific and
      all-cause cost offsets and improved patient outcomes associated with adherence to
      basal insulin therapy for people with T2D. FUNDING: Eli Lilly and Company.

PMID- 29644619
TI  - Early (<= 30 Days), Late (31-360 Days) and Very Late (> 360 Days) Stent
      Thrombosis in Patients with Insulin-Treated versus Non-Insulin-Treated Type 2
      Diabetes Mellitus: A Meta-Analysis.
AB  - INTRODUCTION: At this time in 2018, with type 2 diabetes mellitus (T2DM) and
      coronary artery disease (CAD) still on the rise, the post-percutaneous coronary
      interventional (PCI) outcomes observed in patients with diabetes mellitus who are
      on insulin therapy (ITDM) and those who do not require insulin (NITDM) are still
      controversial and require further investigation. Considering this idea to be of
      particular interest to the readers, as well as being an important issue in
      interventional cardiology, we aimed to systematically assess early (<= 30 days),
      late (31-360 days) and very late (> 360 days) stent thrombosis in patients with
      ITDM and NITDM following drug-eluting stent (DES) implantation. METHODS: Well
      known online databases (the Cochrane, EMBASE and MEDLINE databases and
      http://www.ClinicalTrials.gov ) were searched for relevant English publications
      based on ITDM and NITDM and stent thrombosis following PCI using specific terms.
      Early stent thrombosis, late stent thrombosis and very late stent thrombosis were
      the clinical outcomes. The main analysis was carried out using the latest version
      of the RevMan software (version 5.3) whereby odds ratios (OR), and 95% confidence
      intervals (CI) were generated. RESULTS: A total of 8524 participants with T2DM
      (2273 participants were on insulin therapy and 6251 participants were not) were
      included. Results of this analysis showed early stent thrombosis to be
      significantly higher in patients with ITDM (OR 1.81, 95% CI 1.04-3.15; P = 0.04),
      whereas late and very late stent thromboses were not significantly different
      following PCI with DES in diabetic patients with versus without insulin therapy
      (OR 1.44, 95% CI 0.73-2.84, P = 0.30 and OR 0.80, 95% CI 0.33-1.92, P = 0.62,
      respectively). Late stent thromboses associated exclusively with everolimus
      eluting stents (EES) and paclitaxel-eluting stents (PES) were not significantly
      different in patients with ITDM and NITDM. CONCLUSION: Following PCI with DES,
      early stent thrombosis was significantly higher in patients with ITDM. However,
      late and very late stent thromboses were not significantly different in patients
      with type 2 diabetes mellitus who were treated with or without insulin.
      Comparison with individual DES was not sufficiently powerful to reach a
      conclusion.

PMID- 29644620
TI  - Mine land rehabilitation in Brazil: Goals and techniques in the context of legal
      requirements.
AB  - Environmental legislation in many countries demands the rehabilitation of
      degraded areas to minimize environmental impacts. Brazilian laws require the
      restitution of self-sustaining ecosystems to historical conditions but ignore the
      emergence of novel ecosystems due to large-scale changes, such as species
      invasions, extinctions, and land-use or climate changes, although these novel
      ecosystems might fulfill ecosystem services in similar ways as historic
      ecosystems. Thorough discussions of rehabilitation goals, target ecosystems,
      applied methods, and approaches to achieving mine land rehabilitation, as well as
      dialogues about the advantages and risks of chemical inputs or non-native, non
      invasive species that include all political, economic, social, and academic
      stakeholders are necessary to achieve biological feasibility, sociocultural
      acceptance, economic viability, and institutional tractability during
      environmental rehabilitation. Scientific knowledge of natural and rehabilitating
      ecosystems is indispensable for advancing these discussions and achieving more
      sustainable mining. Both mining companies and public institutions are responsible
      for obtaining this knowledge.

PMID- 29644622
TI  - Microbial metabolites, short-chain fatty acids, restrain tissue bacterial load,
      chronic inflammation, and associated cancer in the colon of mice.
AB  - The intestinal immune system is regulated by microbes and their metabolites. The
      roles of gut microbial metabolites in regulating intestinal inflammation and
      tumorigenesis are incompletely understood. We systematically studied the roles of
      short-chain fatty acids (SCFAs) and their receptors (GPR43 or GPR41) in
      regulating tissue bacterial load, acute versus chronic inflammatory responses,
      and intestinal cancer development. SCFA receptor-, particularly GPR43-, deficient
      mice were defective in mounting appropriate acute immune responses to promote
      barrier immunity, and developed uncontrolled chronic inflammatory responses
      following epithelial damage. Further, intestinal carcinogenesis was increased in
      GPR43-deficient mice. Dietary fiber and SCFA administration suppressed intestinal
      inflammation and cancer in both GPR43-dependent and independent manners. The
      beneficial effect of GPR43 was not mediated by altered microbiota but by host
      tissue cells and hematopoietic cells to a lesser degree. We found that inability
      to suppress commensal bacterial invasion into the colonic tissue is associated
      with the increased chronic Th17-driven inflammation and carcinogenesis in the
      intestine of GPR43-deficient mice. In sum, our results reveal the beneficial
      function of the SCFA-GPR43 axis in suppressing bacterial invasion and associated
      chronic inflammation and carcinogenesis in the colon.

PMID- 29644621
TI  - Exploring dynamism of cultural ecosystems services through a review of
      environmental education research.
AB  - The field of cultural ecosystem services (CES) explores the non-material benefits
      that ecosystems provide to people. Human perceptions and valuations change, for
      many reasons and in many ways; research on CES, however, rarely accounts for this
      dynamism. In an almost entirely separate academic world, research on
      environmental education (EE) explores how EE programming affects peoples'
      attitudes and values toward the natural world. In this review of 119 EE research
      publications, we explore whether CES (and the adjacent concept of relational
      values) can be dynamic. We approach this via two lines of inquiry that explore
      whether EE may instigate this change. First, we investigate whether the EE
      community measures (and tries to affect) CES-related outcomes. Second, we ask:
      Has EE research detected changes in CES-related outcomes? We find the EE programs
      measure many CES outcomes (e.g., aesthetic appreciation, social connectedness),
      and that in most cases studies observe increases in these outcomes after EE
      experiences.

PMID- 29644623
TI  - Single Pass Diafiltration Integrated into a Fully Continuous mAb Purification
      Process.
AB  - The concept of continuous manufacturing has gained significant interest from the
      biopharmaceutical industry over the past several years. Benefits include
      increased manufacturing productivity, improved quality control, reduction in
      plant footprint, and more flexible management of facility capacity. There are
      several technologies currently available that enable continuous processing for
      chromatography and ultrafiltration. However, a single pass diafiltration design
      that meets the required small molecule clearance and has been integrated into a
      fully continuous monoclonal antibody purification process has not been previously
      published. Here, the theory and design of a 3-stage single pass diafiltration
      step is presented. Buffer exchange greater than 99.75% was experimentally
      demonstrated. Several critical design aspects were incorporated to minimize
      system complexity and reduce the buffer volume requirements. Lastly, single pass
      diafiltration was demonstrated in a pilot scale continuous process with
      uninterrupted flow from the bioreactor through the formulation step. This work
      illustrates the feasibility of incorporating a single pass diafiltration step
      into an end-to-end continuous protein purification process. This article is
      protected by copyright. All rights reserved.

PMID- 29644624
TI  - The demographic history of Atlantic salmon (Salmo salar) across its distribution
      range reconstructed from approximate Bayesian computations.
AB  - Understanding the dual roles of demographic and selective processes in the
      buildup of population divergence is one of the most challenging tasks in
      evolutionary biology. Here, we investigated the demographic history of Atlantic
      salmon across the entire species range using 2035 anadromous individuals from
      North America and Eurasia. By combining results from admixture graphs, geo
      genetic maps, and an Approximate Bayesian Computation (ABC) framework, we
      validated previous hypotheses pertaining to secondary contact between European
      and Northern American populations, but also identified secondary contacts in
      European populations from different glacial refugia. We further identified the
      major sources of admixture from the southern range of North America into more
      northern populations along with a strong signal of secondary gene flow between
      genetic regional groups. We hypothesize that these patterns reflect the spatial
      redistribution of ancestral variation across the entire North American range.
      Results also support a role for linked selection and differential introgression
      that likely played an underappreciated role in shaping the genomic landscape of
      species in the Northern hemisphere. We conclude that studies between partially
      isolated populations should systematically include heterogeneity in selective and
      introgressive effects among loci to perform more rigorous demographic inferences
      of the divergence process.

PMID- 29644629
TI  - A3. Vaginal intraepithelial neoplasia (VAIN).
AB  - VAIN is much rarer than the equivalent dysplastic changes found in the cervix but
      may accompany cervical intraepithelial neoplasia. VAIN is also HPV in-duced and
      may be an extension of a cervical lesion or a satellite lesion. VAIN lesions are
      usually asymptomatic and detected by cytologic screening. Lesions can be ex
      cised, vaporized or treated locally with medical therapies. The incidence of
      vaginal cancer is very rare.

PMID- 29644627
TI  - Routinely used immunoassays do not detect circulating anti-GBM antibodies against
      native NC1 hexamer and EA epitope of the alpha3 chain of type IV collagen.
AB  - Detection of circulating anti-GBM antibodies has a key role for the diagnosis of
      Goodpasture syndrome but immunoassays using purified or recombinant alpha3(IV)NC1
      as antigen do not recognize all anti-GBM antibodies. We show that anti-GBM
      antibodies directed against epitopes in their native conformation or cryptic
      epitopes are detected by indirect immunofluorescence.

PMID- 29644630
TI  - CHAPTER 3 Pathology of HPV infection at the cytologic and histologic levels:
      Basis for a 2-tiered morphologic classification system.
AB  - Over the last 2 decades the pathogenesis and natural history of cervi-cal cancer
      has become clearer. As a result, the cytologic and histologic terminol-ogy used
      to refer to cervical cancer precursors has needed to change. Today we recognize
      that almost all cervical cancers are due to infection with specific high-risk
      types of human papillomavirus (HPV). Most women become infected with these
      viruses within several years of initiating sexual intercourse and a productive
      HPV in-fection frequently results in characteristic morphologic changes within
      the infected cervical squamous cells. Cells demonstrating the morphologic changes
      associated with a productive HPV infection are referred to as low-grade squamous
      intraepi-thelial lesions (LSIL) when observed in cytologic specimens and low
      grade cervical intraepithelial neoplasia (CIN 1) when observed in histologic
      specimens. In some women, HPV gene expression becomes unlinked to the state of
      differentiation of the infected epithelial cells and deregulated expression of
      the early region of the viral genome results in a dramatic increase in expression
      of two HPV oncoproteins (E6 and E7). This results in loss of normal cell cycle
      control of the epithelium and genetic instability. When this occurs the
      epithelium develops characteristic mor-phologic features, with immature "basaloid
      type" squamous cells and mitotic fig-ures in the upper half of the cervical
      epithelium. Such lesions are felt to represent "true" neoplasia and are referred
      to as high-grade squamous intraepithelial lesions (HSIL) when observed in
      cytologic specimens and high-grade cervical intraepithelial neoplasia (CIN 2,3)
      when observed in histologic specimens.

PMID- 29644631
TI  - A4. Preinvasive lesions of the cervix.
AB  - Low-risk human papillomaviruses (HPVs) can cause genital warts which, although
      benign, may provoke psychological distress because they are sexually transmitted.
      High-risk HPVs can cause cervical intraepithelial neoplasia and cancer. Cytology
      based screening programs have significantly reduced cervical cancer morbidity and
      mortality where the programs have been successfully implemented.
      Womenwithabnormalcervicalsmearsare referred for colposcopic assessment, which may
      confirm the presence of a preinvasive lesion;allows the grade and extent of the
      lesion to be defined;and guides the colposcopist as to the most appropriate site
      for biopsy and histologic confirmation of the lesion. Excision of the
      transformation zone of the cervix in an outpatient setting using local anesthetic
      has greatly simplified the treatment of premalignant lesions, but long-term
      follow-up is essential to ensure that the lesions neither persist nor recur.
      Abnormal cytologic findings during adolescence and pregnancy need special
      management.

PMID- 29644632
TI  - CHAPTER 10 A public health approach to cervical cancer control: Considerations of
      screening and vaccination strategies.
AB  - Cervical cancer remains a leading cause of cancer death among women living in low
      resource settings. In the last 3 decades, cytologic screening has -in theory 
      been available and yet more than 6 million women have died of this preventable
      disease. The necessary resources, infrastructure, and technological expertise,
      together with the need for repeated screenings at regular intervals, make
      cytologic screening difficult to implement in poor countries. As noncytologic
      approaches for the detection of HPV, simple visual screening methods for
      anogenital lesions caused by HPV, and the availability of an HPV-16/18 vaccine
      will enhance the linkage between screening and treatment, multiple factors will
      need to be considered when designing new, or modifying existing prevention
      strategies. Countryspecific decisions regarding the best strategy for cervical
      cancer control will need to rely on data from many sources and take into account
      complex epidemiologic, economic, social, political, and cultural factors, and be
      made despite uncertainty and incomplete information. A rigorous decision analytic
      approach using computerbased modeling methods enables linkage of the knowledge
      gained from empirical studies to real-world situations. This chapter provides an
      introduction to these methods, reviews lessons learned from cost-effectiveness
      analyses of cervical cancer screening in developed and developing countries, and
      emphasizes important qualitative themes to consider in designing cervical cancer
      prevention policies.

PMID- 29644633
TI  - CHAPTER 2 The epidemiology of human papillomavirus infection and its association
      with cervical cancer.
AB  - Cervical cancer has been recognized as a rare outcome of a common, sexually
      transmitted infection whose etiologic association is restricted to a few human
      papillomavirus (HPV) types. With optimal testing systems HPV DNA can be
      identified in nearly all specimens of invasive cervical cancer, and it is claimed
      that infection of the cervix with HPV is a necessary cause of cervical cancer.
      The evidence is consistent worldwide for squamous cell carcinomas (SCC),
      adenocarcinomas, and the vast majority (>95%) of the immediate cervical cancer
      precursors, namely high-grade squamous intraepithelial lesions (HSILs)-also known
      as cervical intraepithelial neoplasia 3 (CIN 3) or carcinoma in situ. Cofactors
      that modify the risk for HPV DNA-positive women include the use of oral
      contraceptives (OCs) for 5 or more years, smoking, high parity (5 or more full
      term pregnancies), and previ-ous exposure to other sexually transmitted diseases
      such as Chlamydia trachomatis and herpes simplex virus type 2 (HSV-2). Women
      exposed to the human immuno-deficiency virus (HIV) are at high risk for HPV
      infection, HPV DNA persistence, and progression of HPV lesions to cervical
      cancer.

PMID- 29644634
TI  - Section B: Malignant manifestations of HPV infection Carcinoma of the cervix,
      vulva, vagina, anus, and penis.
AB  - Cervical cancer remains the commonest cancer among women in developing countries,
      affecting women at their peak of social and economic responsibility. In poor
      countries where access to diagnosis and treatment is extremely limited, most of
      the affected women present with late-stage disease. Many do not even have access
      to palliative care. Outcome in women treated for cervical cancer is strongly
      influenced by the stage of diagnosis. The main treatment modalities remain
      surgical removal for early-stage disease and chemoradiation for late-stage
      disease. Cancers of the vulva, vagina, penis, and anus are much less common than
      cervical cancer although, in most cases, they also are associated with human
      papillomavirus infection. Diagnosis and chief treatment modalities for cervical
      and these less common cancers are discussed.

PMID- 29644635
TI  - CHAPTER 4 Clinical manifestations of HPV infection Section A: Benign
      manifestations of HPV infection: A1. Anogenital condylomas.
AB  - The clinical manifestation of infection with HPV is determined by multi-ple
      factors which include the type of HPV, the type of skin infected, the status of
      host immunity and smoking. The incubation period for HPV is 3 weeks to 8 months.
      While there is no specific anti-HPV therapy, local topical therapy, excision,
      cautery and laser vaporization have all been used with a range of success rates.

PMID- 29644636
TI  - CHAPTER 6 Secondary prevention of cervical cancer.
AB  - Cervical cancer continues to be the commonest cause of death among women in
      developing countries, largely due to the failure to initiate or sustain effective
      cytology-based screening programs. Experience from countries with successful
      screening programs indicates that target age and the extent of coverage of the
      target group are key indicators of success in reducing cervical cancer.
      Alternative methods for the secondary prevention of cervical cancer have been
      evaluated in numerous studies over the past 10 years in different countries.
      These include visual inspection with acetic acid and linking screening to
      treatment. Although longitudinal data are scanty, these alternative approaches
      have been shown to be feasible, acceptable, and effective in reducing cervical
      cancer.

PMID- 29644637
TI  - A2. Vulval intraepithelial neoplasia (VIN).
AB  - VIN 3 is most likely a cancer precursor and is induced by infection with high
      risk types of HPV. VIN 3 lesions may be asymptomatic or present with itching
      and/or burning or the appearance of a vulval lesion (often raised and hyperpig
      mented), which may be unifocal or multifocal. All vulval lesions should be
      biopsied to confirm the diagnosis. Treatment options include laser vaporization,
      excision or cautery. Long term follow up is essential.

PMID- 29644638
TI  - CHAPTER 1 Biology of genital human papillomaviruses.
AB  - Human papillomaviruses (HPVs) are small DNA viruses that infect various
      epithelial tissues. The more than 100 types of HPV described share a circular DNA
      genome of about 8000 base pairs organized into an early, a late, and a long
      control region. The products of 2 genes from the early control region, E6 and E7,
      are essential in the HPV-induced processes of cellular transformation and
      immortalization, and 2 genes from the late control region, L1 and L2, encode the
      viral capsid proteins. A few high-risk types of HPV types, including HPV-16 and
      HPV-18, are asso-ciated with more than 99% of cervical carcinomas. Continuous
      expression of the E6 and E7 oncoproteins by high-risk types of HPV often leads to
      genomic aberrations, a step toward malignant conversion. Although in most cases
      innate and adaptive im-mune responses control HPV infection, the high-risk types
      of virus have the ability to subvert immune defenses, which explains persistent
      infection and progression to neoplasia.

PMID- 29644639
TI  - CHAPTER 11 How to manage and communicate with patients about HPV?
AB  - The whole concept of abnormal Pap smears and cervical cancer being due to an STI
      poses enormous challenges to the healthcare provider. The psychological and
      psychosocial sequelae of misinformation are potentially damaging both to the
      woman and her partner. There is a clear responsibility for the information around
      this to be simple, relevant, reassuring and comprehensible. Written information
      is invaluable.

PMID- 29644640
TI  - CHAPTER 7 Methods for detection of HPV infection and its clinical utility.
AB  - HPVs cannot be cultured and the detection of virus relies on a variety of
      techniques used in immunology, serology, and molecular biology. Currently the
      only FDA-approved commercially available method for the detection of HPV DNA is
      the Hybrid Capture assay, version hc2 (Digene, Gaithersburg, MD, USA) which is
      able to detect 13 high-risk types of HPV. The advantage of PCR-based methods of
      HPV DNA detection is that they allow for the identification of different types of
      HPV. This article discusses the advantages and disadvantages of the different
      methods of HPV DNA detection. HPV DNA testing can be used in a variety of
      clinical scenarios that include a primary screening test, particularly in women
      older than 30 years;as an adjunctive test to cytology;to triage women who have an
      equivocal cytologic finding, e.g., ASC-US, or for follow up post-treatment. In
      addition, HPV DNA testing can be performed on samples obtained by women
      themselves (so-called self-sampling), which may be useful in women who are
      resistant to undergoing gynecologic examinations.

PMID- 29644641
TI  - From the Editors.

PMID- 29644642
TI  - CHAPTER 8 HPV vaccines.
AB  - Vaccines to prevent infection with high-risk human papillomaviruses (HPV) will
      help protect women against cervical cancer, and some are likely to be available
      within the next year. One vaccine, a quadrivalent vaccine against HPV types 6,
      11, 16 and 18 and known as Garadsil (c)(Merck &Co., Inc), was approved by the
      Federal Drug Administration (FDA) for the prevention of cervical cancer, cervical
      cancer precursors and vulval and vaginal cancer precursors associated with HPV 16
      and 18 in June 2006. In addition, the vaccine has been approved for the
      prevention of genital warts and low grade cervical lesions e.g. cervical
      intraepithelial neoplasia1. The main vaccines components are recombinant viral
      capsid proteins assembled into virus-like particles and alum-based adjuvants. If
      given before HPV infection, the vaccines, which induce HPV type-specific, virus
      neutralizing antibodies, have proven safe and highly effective at preventing HPV
      infection and its clinical consequences, including high-grade cervical lesions.
      Their use should not immediately alter existing screening programs for cervical
      cancer, however. Because they incorporate only the 2 HPV types most commonly
      associated with cervical cancer (HPV-16 and HPV-18), they can only prevent about
      70% of cervical cancers. Vaccines to treat existing HPV infection are under
      development but are unlikely to become clinically available in the near future.

PMID- 29644643
TI  - Foreword.

PMID- 29644644
TI  - CHAPTER 5 HPV infection and HPV-associated neoplasia in immunocompromised women.
AB  - Human immunodeficiency virus (HIV)-positive women and women with transplant
      associated immunocompromise are at increased risk for cervical intraepithelial
      neoplasia (CIN) and cervical cancer compared with healthy, immunocompetent women.
      HPV often manifests as a "field" effect in immunocompromised women who are also
      at increased risk for vaginal, vulval, and anal intraepithelial neoplasia.
      Immunocompromised women require careful follow-up with regular cy-tologic
      screening, and there should be a low threshold for performing colposcopic
      evaluation in these women. Once detected, CIN should be treated aggressively and
      the patient followed up closely for recurrence. Although treatment regimens are
      similar for immunocompromised and healthy women, the former may need multiple
      treatment modalities. Data on the ability of highly active antiretroviral therapy
      (HAART) to reduce the incidence of high-grade CIN and on the regression of
      existing CIN are mixed, some studies showing no benefit and others a modest
      benefit from HAART. However, the incidence of cervical cancer has not declined
      since the introduction of HAART, and the use of HAART among HIV-positive women
      has not changed the suggested approach to cervical cancer screening and
      treatment. Finally, prophylactic HPV vaccination offers the possibility of
      reducing the burden of disease among immunocompromised women, particularly if
      they are vaccinated before the onset of both sexual activity and
      immunocompromise. However, studies are needed to document safety and
      immunogenicity, and -given their high rate of prior HPV exposure -the
      effectiveness of the vaccine in these women.

PMID- 29644645
TI  - CHAPTER 9 Delivering HPV vaccine in the industrial and developing world: the role
      of the ob-gyn community.
AB  - The development and demonstration of the safety and effectiveness of new HPV
      vaccines is a major breakthrough in medical science that could prevent most cases
      of cervical cancer, the first or second cause of cancer death in women in most
      developing countries. This chapter discusses the delivery of HPV vaccine in the
      industrial and developing world, from the point of view of what obstetricians and
      gynecologists need to know to use and advocate for the use of this powerful new
      tool.

PMID- 29644646
TI  - A review of postoperative care for obstetric fistulas in Nigeria.
AB  - Nigeria harbors an estimated 40% of all the women affected with obstetric
      fistulas today, and at the current rate of treatment in this country, it would
      take about 300 years to treat them if no new fistulas occurred. This situation
      obviously runs contrary to the ideals of the United Nations Millennium
      Development Goals and needs to be reversed. We reviewed the literature on fistula
      treatment in Nigeria to identify strategies and practices that, if adopted, would
      likely accelerate the pace of fistula repair and improve postoperative fistula
      care in this country. A comprehensive nationwide survey, a stronger political
      will and commitment of resources, a systematic postoperative care and follow-up,
      more fistula centers, and more fistula campaigns are necessary. Technically, the
      involvement of all surgeons trained in fistula repair and an experience-based
      postoperative management protocol will relieve the disease burden carried by
      women living with fistulas in Nigeria.

PMID- 29644647
TI  - Free Communication (Oral) Presentations.

PMID- 29644648
TI  - Invited Presentations and Presentations by Organizations and Societies.

PMID- 29644650
TI  - Executive Board.

PMID- 29644649
TI  - Poster Presentations.

PMID- 29644651
TI  - Improving maternal and perinatal outcomes in the hypertensive disorders of
      pregnancy: A vision of a community-focused approach.
AB  - The hypertensive disorders of pregnancy (HDP; pre-existing hypertension,
      gestational hypertension, and pre-eclampsia) remain important causes of maternal
      morbidity and mortality, especially in low- and middle-income countries. The
      paper summarizes the current state of evidence around possible technologies to
      support community-based improvements in maternal and perinatal outcomes for women
      with pre-eclampsia. Through the testing and, where proven, introduction of these
      technologies, we believe that HDP-related progress toward achieving Millennium
      Development Goal 5 can best be accelerated. The evidence and discussion are
      presented under the following headings: (1) prediction; (2) prevention; (3)
      diagnosis; (4) risk stratification; (5) decision aids; (6) treatment; (7)
      geographic information systems; (8) communication; and (9) community and patient
      education.

PMID- 29644654
TI  - The International Federation of Gynecology and Obstetrics (FIGO) Initiative on
      gestational diabetes mellitus: A pragmatic guide for diagnosis, management, and
      care.

PMID- 29644658
TI  - Carcinoma of the Vagina.

PMID- 29644659
TI  - Cervical Cancer: The South African Perspective.

PMID- 29644660
TI  - Cervical Cancer: The Indian Perspective.
AB  - Cancer of the uterine cervix is the commonest gynaecologic cancer in India, with
      most women presenting with disease extending beyond the cervix. The majority of
      women belong to the lower socioeconomic status, are rural, aged between 35 and 64
      years and highly noncompliant for complete treatment and follow-up. Opportunistic
      screening with cytology, colposcopy and test for Human Papilloma Virus and
      appropriate treatment are available on payment at urban private medical centres
      but are not available at urban and rural government health centres that are
      accessed by women of the lower socioeconomic status. The Government's investment
      in health is 0.9% of the GDP. Thus cytology screening as a government health
      measure is not feasible. The 'social vaccine' of health empowerment along with
      visual inspection and appropriate referral by the rural and urban health
      personnel (Department of Health and Family Welfare); with an additional input of
      health awareness and motivation by Anganwadi Workers (Department of Women and
      Child Development), elected women representatives in the Panchayats (Department
      of Rural Development and Panchayati Raj) and non-governmental development
      agencies could be a collaborative effort towards "downstaging" cervical cancer.
      This could lay the foundation for the introduction of cytology screening when
      resources are available.

PMID- 29644661
TI  - Carcinoma of the Corpus Uteri.

PMID- 29644663
TI  - History of the Annual Report.

PMID- 29644662
TI  - Carcinoma of the Fallopian Tube.

PMID- 29644664
TI  - Materials and Methods.

PMID- 29644665
TI  - From the Editor.

PMID- 29644666
TI  - Quality of Life Considerations in Gynecologic Cancer.
AB  - Quality of life (QOL) is a fundamental consideration for patients with life
      threatening diseases. Major evolving paradigms are discussed: improved QOL with
      laparoscopic surgery, the impact on QOL of intraperitoneal chemotherapy for
      optimally cytoreduced ovarian cancer, combination therapy, sexuality, and
      survivorship. The goals of treatment for many patients with gynecologic tumors
      remain largely palliative, and patient reported QOL is the primary outcome
      determining the utility of treatment. Particularly in this area, QOL endpoints
      are increasingly important in clinical trials. The QOL issues facing gynecologic
      cancer patients, the use of validated QOL instruments, recent advances in the
      evaluation of interventions, and changes in concepts related to QOL are reviewed.

PMID- 29644667
TI  - FIGO: 27th volume of the ANNUAL REPORT on the Results of Treatment in
      Gynecological Cancer.

PMID- 29644668
TI  - Cervical Cancer: The Chilean Perspective.

PMID- 29644669
TI  - Carcinoma of the Ovary.

PMID- 29644671
TI  - Contributing Centers.

PMID- 29644670
TI  - HPV DNA Testing for Cervical Cancer Screening.

PMID- 29644672
TI  - Why Cancer Staging?

PMID- 29644673
TI  - Carcinoma of the Vulva.

PMID- 29644674
TI  - Overview of Cervical Cancer in the Developing World.

PMID- 29644675
TI  - Gestational Trophoblastic Neoplasia.

PMID- 29644676
TI  - Carcinoma of the Cervix Uteri.

PMID- 29644678
TI  - The safety of misoprostol.

PMID- 29644677
TI  - Preliminary progress report: Randomized double-blind trial of Zhi Byed 11, a
      Tibetan traditional medicine, versus misoprostol to prevent postpartum hemorrhage
      in Lhasa, Tibet.

PMID- 29644679
TI  - Global availability of misoprostol.

PMID- 29644680
TI  - Prevention of postpartum hemorrhage: The role of active management of the third
      stage of labor.

PMID- 29644681
TI  - Public-private partnership in health research.

PMID- 29644682
TI  - Controlled cord traction in the third stage of labor. Systematic review.

PMID- 29644683
TI  - A double-blind randomized controlled trial to compare sublingual misoprostol with
      methylergometrine for prevention of postpartum hemorrhage.

PMID- 29644684
TI  - Proposed guidelines for management of PPH, essential medicines, measurement of
      blood loss, and issues of skilled birth attendants.
AB  - The statements contained within this article reflect the consensus of the
      assembled body. They do not necessarily reflect complete unanimity of all
      participants.

PMID- 29644685
TI  - Prevention of postpartum haemorrhage at homebirth with use of misoprostol in
      Banke District, Nepal.

PMID- 29644686
TI  - The pilot study of the non-pneumatic anti-shock garment (NASG) in women with
      severe obstetric hemorrhage: Combined results from Egypt and Nigeria.

PMID- 29644688
TI  - A global overview of ongoing misoprostol studies.

PMID- 29644687
TI  - Estimating the effect of unplanned interventions in the randomized misoprostol
      trial: A mixed model analysis.

PMID- 29644689
TI  - Ethical issues in conducting international research studies.

PMID- 29644690
TI  - The role of misoprostol for prevention of postpartum hemorrhage.

PMID- 29644691
TI  - Introduction.

PMID- 29644692
TI  - Creative approaches to rapid assessment and transfer of patients at risk.

PMID- 29644693
TI  - Prevention of postpartum hemorrhage in the absence of uterotonics.

PMID- 29644694
TI  - Training rural health care providers for prevention of PPH.

PMID- 29644695
TI  - From research to practice1.

PMID- 29644696
TI  - Ethical issues in health research: Historical perspectives.

PMID- 29644697
TI  - Rectal misoprostol versus oxytocin in the prevention of postpartum hemorrhage - A
      pilot study.

PMID- 29644698
TI  - The efficacy of oral misoprostol in preventing postpartum hemorrhage in a
      community setting: A randomized double-blind placebo-controlled trial.

PMID- 29644699
TI  - Prevalence of daily flossing among adults by selected risk factors for
      periodontal disease-United States, 2011-2014.
AB  - BACKGROUND: Daily flossing prevalence was determined among adults >=30 years old
      in the United States, by demographic and risk factors for periodontal disease,
      including current tobacco use and diabetes. METHODS: Data from the 2011-2014
      National Health and Nutrition Examination Survey were analyzed for 8,356 adults.
      Flossing prevalence was estimated. Logistic regression analysis examined the
      association between daily flossing and demographic and risk factors for
      periodontal diseases. RESULTS: Daily flossing among adults was 31.6% (standard
      error [SE] = 0.8). There were significant differences among the categories of
      flossing according to age, sex, race/Hispanic origin, poverty status, education,
      current tobacco use, and diabetes status. In adjusted analyses, current tobacco
      users (odds ratio [OR]: 0.82; 95% confidence index [CI] 0.68, 0.99) had lower
      odds of daily flossing than non-tobacco users; there was no significant
      difference between adults with and without diabetes (OR 0.75; 95% CI 0.52, 1.08).
      CONCLUSION: Approximately one-third of adults in the United States reported that
      they floss daily. Daily flossing was higher among women, those with higher
      income, and non-Hispanic Asian and Hispanic adults, but it was lower among
      current tobacco users.

PMID- 29644700
TI  - SNP-based susceptibility-resistance association and mRNA expression regulation
      analyses of tlr7 to grass carp Ctenopharyngodon idella reovirus.
AB  - Eleven single nucleotide polymorphisms (SNP) in Ctenopharyngodon idella toll-like
      receptor 7 (citlr7) gene, containing two in the 5'-flanking region, three within
      the single intron and six distributed in the coding sequence (CDS), were
      identified. A case-control study of 73 susceptible individuals and 67 resistant
      individuals was conducted to test the SNPs-based susceptibility-resistance
      association and mRNA expression of citlr7 to grass carp reovirus (GCRV), showing
      that both 820 A/G and 1726 A/G were significantly correlative sites in genotype
      (P < 0.05). Multifactor dimensionality reduction (MDR) analysis suggested the
      exertion of antiviral effects of 820 A/G might rely on SNPs interactions of
      citlr7 and C. idella toll-like receptor 8 (citlr8). Combining the mortality rate
      and citlr7 mRNA expression, it was suggested that 1726 GG-genotyped individuals
      might be more resistant than 1726 A/G genotyped individuals, indicating the
      selection on synonymous mutations in 1726 A/G might be susceptibility-resistance
      type specific. In addition, haplotype analysis uncovered no significantly
      correlative haplotypes in citlr7. These findings may provide an in-depth insight
      for the further functional research of citlr7. The potential genetic markers
      identified may contribute to the molecular and transgenic breeding of C. idella.

PMID- 29644704
TI  - Close but not quite: Two cases of sex chromosome aneuploidies outside the scope
      of cell free DNA screening.

PMID- 29644702
TI  - Influence of group III/IV muscle afferents on small muscle mass exercise
      performance: a bioenergetics perspective.
AB  - KEY POINTS: This investigation assessed the influence of group III/IV muscle
      afferents on small muscle mass exercise performance from a skeletal muscle
      bioenergetics perspective. Group III/IV muscle afferent feedback was attenuated
      with lumbar intrathecal fentanyl during intermittent isometric single-leg knee
      extensor all-out exercise, while 31 P-MRS was used to assess skeletal muscle
      bioenergetics. Attenuation of group III/IV muscle afferent feedback improved
      exercise performance during the first minute of exercise, due to an increase in
      total ATP production with no change in the ATP cost of contraction. However,
      exercise performance was not altered during the remainder of the protocol,
      despite a sustained increase in total ATP production, due to an exacerbated ATP
      cost of contraction. These findings reveal that group III/IV muscle afferents
      directly limit exercise performance during small muscle mass exercise, but, due
      to their critical role in maintaining skeletal muscle contractile efficiency,
      with time, the benefit of attenuating the muscle afferents is negated. ABSTRACT:
      The direct influence of group III/IV muscle afferents on exercise performance
      remains equivocal. Therefore, all-out intermittent isometric single-leg knee
      extensor exercise and phosphorous magnetic resonance spectroscopy (31 P-MRS) were
      utilized to provide a high time resolution assessment of exercise performance and
      skeletal muscle bioenergetics in control conditions (CTRL) and with the
      attenuation of group III/IV muscle afferent feedback via lumbar intrathecal
      fentanyl (FENT). In both conditions, seven recreationally active men performed 60
      maximal voluntary quadriceps contractions (MVC; 3 s contraction, 2 s relaxation),
      while knee-extensor force and 31 P-MRS were assessed during each MVC. The
      cumulative integrated force was significantly greater (8 +/- 6%) in FENT than
      CTRL for the first minute of the all-out protocol, but was not significantly
      different for the second to fifth minutes. Total ATP production was significantly
      greater (16 +/- 21%) in FENT than CTRL throughout the all-out exercise protocol,
      due to a significantly greater anaerobic ATP production (11 +/- 13%) in FENT than
      CTRL with no significant difference in oxidative ATP production. The ATP cost of
      contraction was not significantly different between FENT and CTRL for the first
      minute of the all-out protocol, but was significantly greater (29 +/- 34%) in
      FENT than in CTRL for the second to fifth minutes. These findings reveal that
      group III/IV muscle afferents directly limit exercise performance during small
      muscle mass exercise, but, due to their critical role in maintaining skeletal
      muscle contractile efficiency, with time, the benefit from muscle afferent
      attenuation is negated.

PMID- 29644703
TI  - Evaluation of six sample preparation procedures for qualitative and quantitative
      proteomics analysis of milk fat globule membrane.
AB  - Proteomic analysis of membrane proteins is challenged by the proteins solubility
      and detergent incompatibility with MS analysis. No single perfect protocol can be
      used to comprehensively characterize the proteome of membrane fraction. Here, we
      used cow milk fat globule membrane (MFGM) proteome analysis to assess six sample
      preparation procedures including one in-gel and five in-solution digestion
      approaches prior to LC-MS/MS analysis. The largest number of MFGM proteins were
      identified by suspension trapping (S-Trap) and filter-aided sample preparation
      (FASP) methods, followed by acetone precipitation without clean-up of tryptic
      peptides method. Protein identifications with highest average coverage was
      achieved by Chloroform/MeOH, in-gel and S-Trap methods. Most distinct proteins
      were identified by FASP method, followed by S-Trap. Analyses by Venn diagram,
      principal-component analysis, hierarchical clustering and the abundance ranking
      of quantitative proteins highlight differences in the MFGM fraction by the all
      sample preparation procedures. These results reveal the biased proteins/peptides
      loss occurred in each protocol. In this study, we found several novel proteins
      that were not observed previously by in-depth proteomics characterization of MFGM
      fraction in milk. Thus, a combination of multiple procedures with orthologous
      properties of sample preparation was demonstrated to improve the protein sequence
      coverage and expression level accuracy of membrane samples.

PMID- 29644705
TI  - A fully validated method for the simultaneous determination of 11 antihistamines
      in breast milk by gas chromatography-mass spectrometry.
AB  - Antihistamines are excreted into breast milk in small amounts; however, there are
      no adequate published studies or data concerning their effects on newborns and
      safety during breastfeeding. Thus, the development of sensitive and specific
      methodologies for the determination of antihistamines in breast milk is critical.
      A simple and sensitive GC-MS method for the simultaneous determination of 11
      antihistamines (diphenhydramine, orphenadrine, chlorpheniramine, dimethindene,
      meclozine, hydroxyzine, loratadine, desloratadine, cetirizine, rupatadine and
      ebastine) in breast milk was developed and validated. The antihistamines were
      solid-phase extracted and derivatized with acetic anhydride and n-propanol.
      Diazepam-d5 , hydroxyzine-d4 and cetirizine-d8 were used as internal standards.
      Absolute recovery values for all analytes ranged from 70.5 to 120.0%, while the
      limits of detection and quantification for all analytes were 1.50 and 5.00 ng/mL,
      respectively. All calibration curves were linear (R2  >= 0.990) within the range
      5.00-1000.0 ng/mL. Accuracy (Er ) ranged between -7.6 and 7.0%, while precision
      (RSD) was <12% for all antihistamines. The developed method is suitable for the
      investigation of antihistamine-related clinical cases, as well as for
      pharmacokinetic and breastfeeding safety studies.

PMID- 29644706
TI  - Preparation and evaluation of 188 Re sulfide colloidal nanoparticles loaded
      biodegradable poly (L-lactic acid) microspheres for radioembolization therapy.
AB  - Radioembolization with radioactive microspheres has been an effective method for
      the treatment of liver lesions. The aim of this study was to prepare carrier-free
      188 Re loaded poly (L-lactic acid) (PLLA) microspheres through 188 Re sulfide
      colloidal nanoparticles (188 Re-SC nanoparticles). The formation of 188 Re-SC
      nanoparticles was confirmed by ultraviolet-visible spectrophotometry. The
      labeling yield of 188 Re-SC nanoparticles was verified using the RTLC method.
      Effects of synthesis parameters on morphology and size of prepared 188 Re-sulfide
      colloidal-PLLA microspheres (188 Re-SC-PLLA microspheres) were studied by
      scanning electron microscopy. In vitro stability of 188 Re-SC-PLLA microspheres
      was investigated in normal saline at room temperature and in human serum at 37
      degrees C. In vivo distribution studies and gamma camera imaging were performed
      in healthy BALB/c mice. The microspheres could be prepared with sizes between 13
      and 48 MUm (modal value 29 MUm) and radiolabeling efficiency >99%. After
      incubation, the microspheres were found stable in vitro up to 72 hours. The
      biodistribution after intravenous injection in healthy BALB/c mice showed high
      accumulation in lung as a first capture pathway organ for microsphere followed by
      great retention over 48 hours for these microspheres. These data show that 188 Re
      SC-PLLA microspheres are suitable candidate for clinical studies.

PMID- 29644707
TI  - Perinuclear antineutrophil cytoplasmic antibody-positive vasculitis,
      oligoarthritis, tendinitis, and myositis associated with isotretinoin in a 15
      year-old boy: Case report and review of literature.
AB  - We present a patient in whom a combination of perinuclear antineutrophil
      cytoplasmic antibody-positive vasculitis, oligoarthritis, tendinitis, and
      myositis was considered to be associated with isotretinoin use. Discontinuation
      of the drug resulted in complete clinical and biochemical remission
      (normalization of perinuclear antineutrophil cytoplasmic antibody titer).
      Although we were unable to prove causality, no other underlying cause for the
      patient's course was found. We report this occurrence to bring it to the
      attention of physicians prescribing isotretinoin.

PMID- 29644708
TI  - Reactive oxygen species impact on sperm DNA and its role in male infertility.
AB  - Reactive oxygen species (ROS) have been extensively studied as a cause of male
      infertility. Excessive levels of ROS coupled with a deficiency in antioxidants
      can lead to oxidative stress (OS), which in turn can lead to nuclear and
      mitochondrial DNA damage, telomere shortening, epigenetic alterations and Y
      chromosomal microdeletions. In this review, we discuss how OS induces DNA damage
      and the types of DNA damage that can occur. We also briefly touch on the clinical
      consequences of OS-induced DNA damage.

PMID- 29644709
TI  - Optimizing the pretransplant regimen for autologous stem cell transplantation in
      acute myelogenous leukemia: Better outcomes with busulfan and melphalan compared
      with busulfan and cyclophosphamide in high risk patients autografted in first
      complete remission: A study from the acute leukemia working party of the EBMT.
AB  - Autologous stem cell transplantation remains a clinical option to consolidate
      some adult patients with acute myelogenous leukemia (AML) in first complete
      remission (CR1). In a small cohort of patients, we have previously shown better
      outcomes following Busulfan and Melphalan (BUMEL) over Busulfan and
      Cyclophosphamide (BUCY). To identify the subpopulations that might get the
      highest benefit with BUMEL, we designed a larger study. All adult patients with
      primary AML and available cytogenetics, autografted from January 2000 to December
      2016 in CR1, were included: 1137 patients received BUCY and 512 BUMEL. All
      factors differing in distribution between the 2 conditioning groups were
      introduced in multivariate analyzes. In a primary analysis, we found an
      interaction between conditioning and the poor risk group defined as poor
      cytogenetics and/or presence of the FLT3-ITD mutation. During analysis of the
      poor risk group, 176 patients received BUCY and 62 BUMEL. BUMEL was associated
      with a lower RI at 5 years (53% versus 69%, HR: 0.52, P = .002), a better
      Leukaemia-free survival (LFS) (42% versus 25%, HR: 0.54, P = .002) and a better
      OS (54% versus 36%, HR: 0.61, P = .02). During analysis of the non poor risk
      group, 961 patients received BUCY and 450 BUMEL. At 5 years, the RI was 50% and
      47%, the LFS 45% and 48% and the OS 56% and 60% respectively, with no significant
      difference. We conclude that BUMEL is the preferable conditioning regimen for the
      poor risk leukemic patients, while in AML patients without poor risk cytogenetics
      or FLT3 both conditioning regimens are valid.

PMID- 29644711
TI  - Outlining involvement of stem cell program in regulation of O6-methylguanine DNA
      methyltransferase and development of temozolomide resistance in glioblastoma: An
      Editorial Highlight for 'Transcriptional control of O6 -methylguanine DNA
      methyltransferase expression and temozolomide resistance in glioblastoma' on page
      780.
AB  - Glioblastoma is a malignant brain tumor that inevitably develops resistance to
      standard of care drug temozolomide (TMZ) due to a population of cells called
      cancer stem cells (CSCs). These cells utilize progenitor cell signaling programs
      and develop robust DNA repair machinery. In this editorial highlight we focus on
      stem cell regulation of TMZ resistance and discuss findings of Happold et al. ()
      that outline direct transcriptional regulation of DNA repair enzyme O6
      methylguanine DNA methyltransferase (MGMT) in glioblastoma CSCs through NFkB
      activation. The authors found that cells cultured in CSC propagating conditions
      exhibit increase in MGMT expression when compared to adherent differentiated
      monolayer cells. This in turn increases resistance to standard of care drug
      temozolomide (TMZ) in these cells. NFkB activation was found to directly activate
      expression of MGMT in sphere cultured GBM CSC.

PMID- 29644713
TI  - Deuterium-substituted 2-(2'-((dimethylamino)methyl)-4'-[18
      F](fluoropropoxy)phenylthio)benzenamine as a serotonin transporter imaging agent.
AB  - Positron emission tomography imaging of serotonin transporter (SERT) is useful
      for studying brain diseases with altered serotonergic function. A deuterated
      imaging agent, ([18 F]2-((2-((bis(methyl-d3 )amino)methyl)-4-(3-fluoropropoxy
      1,1,2,2,3,3-d6 )phenyl)thio)aniline, [18 F]D12FPBM, [18 F]1), was prepared as a
      new chemical entity. The deuterated agent, 1, showed excellent binding affinity
      to SERT; Ki was 0.086 nM, comparable with the undeuterated FPBM. In vivo
      biodistribution studies in rats with [18 F]1 showed good brain uptake (1.09%
      dose/g at 2 min post injection) and high specific uptake into the hypothalamus
      (HY) as compared with cerebellum (CB) (HY/CB = 7.55 at 120 min), suggesting a
      specific localization to SERT binding sites. Regional brain distribution in rats
      provided clear indication that [18 F]1 concentrated in the hypothalamus,
      hippocampus, and striatum, areas with a high SERT density. Results indicate that
      very little D to H substitution effect was found; [18 F]FPBM and [18 F]1 showed
      very similar SERT binding. [18 F]1 might be an excellent candidate for SERT
      imaging.

PMID- 29644714
TI  - Design, synthesis, and biological evaluation of 2-substituted-2,3,4,9
      tetrahydrospiro-beta-carboline-3-carboxylic acid derivatives as first-in-class
      mast cell stabilizers.
AB  - Mast cell degranulation plays a momentous role in myriad diseases like asthma,
      eczema, allergic rhinitis, and conjunctivitis as well as anaphylactic shock;
      hence, there is an unmet need for developing new mast cells stabilizers. The
      reported mast cell stabilizers have a heterocyclic moiety and an acidic group.
      Furthermore, the role of tryptophan in suppression of mast cell activation is
      established. Hence, we prepared constrained analogs of tryptophan, which are
      derivatives of 2,3,4,9-tetrahydrospiro-beta-carboline-3-carboxylic acid, and
      evaluated them for ex vivo inhibition of compound 48/80-induced mast
      degranulation activity. By comparing IC50 (MUM) values with that of the standard
      drug sodium cromoglycate (IC50  = 0.489 +/- 0.003 MUM), compounds with bulky
      groups like heptyl (compound 9; IC50  = 0.389 +/- 0.015 MUM) and octyl (compound
      10; IC50  = 0.354 +/- 0.023 MUM) were found to be of similar potency as sodium
      cromoglycate. Furthermore, the polar group-containing compounds like the
      chloropropyl (compound 16; IC50  = 0.382 +/- 0.083 MUM) and benzoyl derivative
      (compound 14; IC50  = 00.469 +/- 0.032 MUM) were also found to be of similar
      potency as sodium cromoglycate. This is a seminal study of spiro-beta-carboline
      mast cell stabilization having a wider scope in mast cell research; yet, the
      mechanism of action remains elusive.

PMID- 29644715
TI  - Comparison of biochemical analysis of fetal serum and fetal urine in the
      prediction of postnatal renal outcome in lower urinary tract obstruction.
AB  - OBJECTIVES: To compare the prognostic value of fetal serum biochemistry and fetal
      urine biochemistry in predicting renal outcome in lower urinary tract obstruction
      (LUTO). METHODS: We retrospectively studied renal outcome following a prenatal
      diagnosis of LUTO in cases for which both fetal blood and fetal urine were
      sampled. We classified the renal outcome as either "favorable," when postnatal
      renal function was normal, or "adverse," in the case of postnatal chronic renal
      failure or when renal histological lesions were present at autopsy in the case of
      termination of pregnancy. A prognostic model was constructed for urine and serum
      separately. beta2-Microglobulin was the only remaining independent predictor in
      fetal urine. beta2-Microglobulin in serum and urine were compared by using
      receiver operating characteristic curves. RESULTS: In the 50 cases included, the
      rate of adverse outcome was 34 of 50(68%): autopsy confirmed severity of renal
      disease in all 27 cases who underwent termination of pregnancy, and among the 23
      live born children, 7 developed renal failure. Fetal serum and urine markers were
      all significantly associated with renal outcome (P < .01). The receiver operating
      characteristic curves for fetal serum and fetal urinary beta2-microglobulin were
      similar (area under the curve = 0.908 versus 0.909, P = .96). CONCLUSION: Fetal
      serum biochemistry and fetal urine biochemistry are of similar prognostic value
      in predicting postnatal renal outcome in fetuses with LUTO.

PMID- 29644718
TI  - REFEREES 2017.

PMID- 29644717
TI  - Diets of reef-dwelling labrids (Choerodon species) vary with body size, season
      and habitat: influence of foraging ability, specialization and opportunism.
AB  - Contemporary multivariate statistics were used to test the hypotheses that the
      dietary compositions of three populations of labrids on the west Australian coast
      are related to body size and undergo seasonal changes and to elucidate the
      relative extents and basis for any dietary differences within and between those
      populations. Gut content analyses determined the dietary compositions of
      Choerodon rubescens in marine waters of the outer reefs in the World Heritage
      Area of Shark Bay (26 degrees  S; 114 degrees  E) and of Choerodon schoenleinii
      in inner protected reefs of that large embayment. The dietary compositions of C.
      rubescens and C. schoenleinii differed significantly among length classes,
      progressed serially with increasing body size, both overall and almost invariably
      in each season and were more closely related to body size than season, whose
      effect was at best minimal. The size-related dietary change in C. rubescens
      involved, in particular, a shift from crustaceans and non-mytilid bivalves to
      mytilid bivalves and echinoid echinoderms. Although the diet of C. schoenleinii
      followed similar size-related changes, it contained a greater volume of
      gastropods when the fish were small and mytilids when large and only a small
      volume of echinoids. The dietary composition of C. rubescens in the Abrolhos
      Islands, 300 km to the south of Shark Bay, was related both to length class and
      season and differed from that of this labrid in Shark Bay with the ingestion of
      lesser volumes of mytilids and greater volumes of echinoids. The size-related
      changes in diet imply that these species shift from foraging over soft substrata
      to over reefs as their very well-developed jaws become sufficiently strong to
      remove attached and larger prey. The dietary compositions of C. rubescens and C.
      schoenleinii in Shark Bay and of C. rubescens at the Abrolhos Islands were
      related far more to habitat-locational differences than to length class and
      season. The above intraspecific and interspecific differences in diet are
      consistent with qualitative accounts of the relative abundances of the main prey
      in their respective environments, supporting the view that, despite
      specializations in their feeding apparatus, these labrids can feed
      opportunistically to a certain extent and could thus potentially respond to
      moderate changes in the composition of their prey caused by climate change and
      other anthropogenic effects.

PMID- 29644716
TI  - Comparison between in vitro and in vivo cartilage overloading studies based on a
      systematic literature review.
AB  - Methodological differences between in vitro and in vivo studies on cartilage
      overloading complicate the comparison of outcomes. The rationale of the current
      review was to (i) identify consistencies and inconsistencies between in vitro and
      in vivo studies on mechanically-induced structural damage in articular cartilage,
      such that variables worth interesting to further explore using either one of
      these approaches can be identified; and (ii) suggest how the methodologies of
      both approaches may be adjusted to facilitate easier comparison and therewith
      stimulate translation of results between in vivo and in vitro studies. This study
      is anticipated to enhance our understanding of the development of osteoarthritis,
      and to reduce the number of in vivo studies. Generally, results of in vitro and
      in vivo studies are not contradicting. Both show subchondral bone damage and
      intact cartilage above a threshold value of impact energy. At lower loading
      rates, excessive loads may cause cartilage fissuring, decreased cell viability,
      collagen network de-structuring, decreased GAG content, an overall damage
      increase over time, and low ability to recover. This encourages further
      improvement of in vitro systems, to replace, reduce, and/or refine in vivo
      studies. However, differences in experimental set up and analyses complicate
      comparison of results. Ways to bridge the gap include (i) bringing in vitro set
      ups closer to in vivo, for example, by aligning loading protocols and overlapping
      experimental timeframes; (ii) synchronizing analytical methods; and (iii) using
      computational models to translate conclusions from in vitro results to the in
      vivo environment and vice versa. (c) 2018 The Authors. Journal of Orthopaedic
      Research(r) Published by Wiley Periodicals, Inc. J Orthop Res 9999:1-11, 2018.

PMID- 29644719
TI  - The profiling and identification of chemical components, prototypes and
      metabolites of Run-zao-zhi-yang capsule in rat plasma, urine and bile by an UPLC
      Q-TOF/MSE -based high-throughput strategy.
AB  - Run-zao-zhi-yang (RZZY) capsule, a traditional Chinese medicine formula, is
      popularly used for the treatment of dermatitis and eczema. However, few studies
      have been carried out on RZZY and its metabolites. In this study, we developed a
      three-step strategy to rapidly characterize the chemical constituents and
      metabolites of RZZY using ultra-high-performance liquid chromatography coupled
      with quadrupole time-of-flight mass spectrometry. A total of 41 chemical
      components were characterized from RZZY. Among these, there are 11 flavonoids,
      six alkaloids, six stilbene glycosides, five anthraquinones and 13 other
      compounds. In addition, 18 prototypes and 35 metabolites were detected in rat
      plasma, urine and bile. This study offers an applicable approach for high
      throughput profiling and identification of chemical components and metabolites
      derived from traditional Chinese medicine formula in vivo, and also provides
      essential data for exploring bioactive ingredients and action mechanisms of RZZY.

PMID- 29644720
TI  - Glitazone in Parkinson's Disease.

PMID- 29644721
TI  - Application of a sensitive and specific LC-ESI-MS/MS method for the simultaneous
      quantification of twelve bioactive components in dog plasma for an intravenous
      pharmacokinetic study of Yiqifumai Injection in beagle dogs.
AB  - Yiqifumai Injection is a lyophilized powder preparation widely used to treat
      coronary heart disease. However, its in vivo bioactive components and
      pharmacokinetic behavior remain unknown. Therefore a sensitive and specific LC
      MS/MS was developed and validated for the simultaneous quantification of eight
      saponins and four lignans in beagle dog plasma. The plasma samples were
      pretreated by protein precipitation with methanol-acetonitrile (1:1, v/v).
      Chromatographic separation of all the 12 analytes and estazolam (internal
      standard, IS) was successfully accomplished on an Ultimate(r) XB-C8 column (100 *
      2.1 mm, 3 MUm) with a gradient elution system. The total running time was 8 min
      with a flow rate of 0.40 mL/min. Acquisition of mass spectrometric data was
      performed via positive electrospray ionization in multiple reaction monitoring
      mode. The assay was fully validated in terms of selectivity, linear range, lower
      limit of quantitation, precision, accuracy, matrix effect, recovery and
      stability. This validated method was successfully applied to the pharmacokinetics
      of 12 bioactive components after intravenous administration of Yiqifumai
      Injection to beagle dogs at a dose of 0.541 g/kg.

PMID- 29644722
TI  - Using machine learning to advance synthesis and use of conservation and
      environmental evidence.

PMID- 29644723
TI  - A French observational study describing the use of human polyvalent
      immunoglobulins in hematological malignancy-associated secondary
      immunodeficiency.
AB  - OBJECTIVE: To describe the characteristics of patients suffering from secondary
      immunodeficiencies (SID) associated with hematological malignancies (HM), who
      started immunoglobulin replacement therapy (IgRT), physicians' expectations
      regarding IgRT, and IgRT modalities. METHODS: Non-interventional, prospective
      French cross-sectional study. RESULTS: The analysis included 231 patients (66 +/-
      12 years old) suffering from multiple myeloma (MM) (N = 64), chronic lymphoid
      leukemia (CLL) (N = 84), aggressive non-Hodgkin B-cell lymphoma (aNHL) (N = 32),
      indolent NHL (N = 39), acute leukemia (N = 6), and Hodgkin disease (N = 6). Of
      the HM, 47% were currently treated, 42% were relapsing or refractory, 23% of
      patients had received an autologous hematopoietic stem-cell transplant, and 1%
      had received an allograft. Serum immunoglobulin trough levels in 195 individuals
      were less than 5 g/L in 68.7% of cases. Most patients had a history of recurrent
      infections. Immunoglobulin dose was about 400 mg/kg/mo. Half of patients started
      with subcutaneous infusion. When starting IgRT, physicians mainly expected to
      prevent severe and moderate infections. They also anticipated improvement in
      quality of life and survival which is beyond evidence-based medicine. CONCLUSION:
      NHL is a frequent condition motivating IgRT besides well-recognized indications.
      Physicians mainly based the decision of starting IgRT on hypogammaglobulinemia
      and recurrence of infections but, irrespective of current recommendations, were
      also prepared to start IgRT prophylactically even in the absence of a history of
      infections.

PMID- 29644725
TI  - Acid-suppressive drugs and risk of kidney disease: A systematic review and meta
      analysis.
AB  - BACKGROUND AND AIM: More concerns had been raised about the risk of kidney
      disease (KD) associated with acid-suppressive drugs. But whether they could
      directly increase such risk remained unclear. Meta-analysis was conducted to
      comprehensively investigate this relationship. METHODS: PubMed, EMBASE, Cochrane
      Central Register of Controlled Trials, and three Chinese databases were searched
      until April 2017 for observational studies investigating the associations between
      acid-suppressive drugs and KD. Pooled log (odds ratios [ORs]) or log (hazard
      ratios [HRs]) with standard errors for KD risk were calculated using the generic
      inverse variance method and random-effect model. RESULTS: Ten studies involving
      128 020 KD patients were included. Proton pump inhibitor (PPI) therapy was
      associated with higher risks of acute interstitial nephritis (OR, 2.78; 95%
      confidence interval [CI], 1.25-6.17), acute kidney injury (AKI) (HR, 1.85; 95%
      CI, 1.33-2.59), chronic kidney disease (CKD) (HR, 1.47; 95% CI, 1.03-2.09), and
      end-stage renal disease (ESRD) (HR, 1.61; 95% CI, 1.26-2.04) than non-PPI
      therapy. Additionally, PPI significantly increased the risks of AKI (HR, 1.32;
      95% CI, 1.16-1.51), CKD (HR, 1.28; 95% CI, 1.24-1.33), and ESRD (HR, 1.96; 95%
      CI, 1.21-3.17) compared with histamine 2 receptor antagonist (H2 RA).
      Relationship between H2 RA therapy and AKI (OR, 0.98; 95% CI, 0.90-1.07) or CKD
      (OR, 1.00; 95% CI, 0.89-1.11) was not found. CONCLUSIONS: Proton pump inhibitor
      therapy significantly increased the risks of acute interstitial nephritis, AKI,
      CKD, and ESRD. Similar risks were not identified for H2 RA therapy. More clinical
      trials are needed to confirm our findings.

PMID- 29644724
TI  - A novel missense mutation in GRIN2A causes a nonepileptic neurodevelopmental
      disorder.
AB  - BACKGROUND: Mutations in the GRIN2A gene, which encodes the GluN2A (glutamate
      [NMDA] receptor subunit epsilon-1) subunit of the N-methyl-d-aspartate receptor,
      have been identified in patients with epilepsy-aphasia spectrum disorders,
      idiopathic focal epilepsies with centrotemporal spikes, and epileptic
      encephalopathies with severe developmental delay. However, thus far, mutations in
      this gene have not been associated with a nonepileptic neurodevelopmental
      disorder with dystonia. OBJECTIVES: The objective of this study was to identify
      the disease-causing gene in 2 siblings with neurodevelopmental and movement
      disorders with no epileptiform abnormalities. METHODS: The study method was
      targeted next-generation sequencing panel for neuropediatric disorders and
      subsequent electrophysiological studies. RESULTS: The 2 siblings carry a novel
      missense mutation in the GRIN2A gene (p.Ala643Asp) that was not detected in
      genomic DNA isolated from blood cells of their parents, suggesting that the
      mutation is the consequence of germinal mosaicism in 1 progenitor. In functional
      studies, the GluN2A-A643D mutation increased the potency of the agonists L
      glutamate and glycine and decreased the potency of endogenous negative
      modulators, including protons, magnesium and zinc but reduced agonist-evoked peak
      current response in mammalian cells, suggesting that this mutation has a mixed
      effect on N-methyl-d-aspartate receptor function. CONCLUSION: De novo GRIN2A
      mutations can give rise to a neurodevelopmental and movement disorder without
      epilepsy. (c) 2018 International Parkinson and Movement Disorder Society.

PMID- 29644726
TI  - Homogeneous Palladium-Catalyzed Transfer Hydrogenolysis of Benzylic Alcohols
      Using Formic Acid as Reductant.
AB  - We report the first homogeneous palladium-based transfer hydrogenolysis of
      benzylic alcohols using an in situ formed palladium-phosphine complex and formic
      acid as reducing agent. The reaction requires a catalyst loading as low as only 1
      mol % of palladium and just a slight excess of reductant to obtain the
      deoxygenated alkylarenes in good to excellent yields. Besides demonstrating the
      broad applicability for primary, secondary and tertiary benzylic alcohols, a
      reaction intermediate could be identified. Additionally, it could be shown that
      partial oxidation of the applied phosphine ligand was beneficial for the course
      of the reaction, presumably by stabilizing the active catalyst. Reaction profiles
      and catalyst poisoning experiments were used to characterize the catalyst, the
      results of which indicate a homogeneous metal complex as the active species.

PMID- 29644727
TI  - Genotype-Phenotype Relations for the Parkinson's Disease Genes Parkin, PINK1,
      DJ1: MDSGene Systematic Review.
AB  - This first comprehensive MDSGene review is devoted to the 3 autosomal recessive
      Parkinson's disease forms: PARK-Parkin, PARK-PINK1, and PARK-DJ1. It followed
      MDSGene's standardized data extraction protocol and screened a total of 3652
      citations and is based on fully curated phenotypic and genotypic data on >1100
      patients with recessively inherited PD because of 221 different disease-causing
      mutations in Parkin, PINK1, or DJ1. All these data are also available in an
      easily searchable online database (www.mdsgene.org), which also provides
      descriptive summary statistics on phenotypic and genetic data. Despite the high
      degree of missingness of phenotypic features and unsystematic reporting of
      genotype data in the original literature, the present review recapitulates many
      of the previously described findings including early onset (median age at onset
      of ~30 years for carriers of at least 2 mutations in any of the 3 genes) of an
      overall clinically typical form of PD with excellent treatment response, dystonia
      and dyskinesia being relatively common and cognitive decline relatively uncommon.
      However, when comparing actual data with common expert knowledge in previously
      published reviews, we detected several discrepancies. We conclude that systematic
      reporting of phenotypes is a pressing need in light of increasingly available
      molecular genetic testing and the emergence of first gene-specific therapies
      entering clinical trials. (c) 2018 International Parkinson and Movement Disorder
      Society.

PMID- 29644728
TI  - 1D Self-Assembly and Ice Recrystallization Inhibition Activity of Antifreeze
      Glycopeptide-Functionalized Perylene Bisimides.
AB  - Antifreeze glycoproteins (AFGPs) are polymeric natural products that have drawn
      considerable interest in diverse research fields owing to their potent ice
      recrystallization inhibition (IRI) activity. Self-assembled materials have
      emerged as a promising class of biomimetic ice growth inhibitor, yet the
      development of AFGP-based supramolecular materials that emulate the aggregative
      behavior of AFGPs have not yet been reported. This work reports the first example
      of the 1D self-assembly and IRI activity of AFGP-functionalized perylene
      bisimides (AFGP-PBIs). Glycopeptide-functionalized PBIs underwent 1D self
      assembly in water and showed modest IRI activity, which could be tuned through
      substitution of the PBI core. This work presents essential proof-of-principle for
      the development of novel IRIs as potential supramolecular cryoprotectants and
      glycoprotein mimics.

PMID- 29644729
TI  - Hydration of Concrete: The First Steps.
AB  - Concrete is the most important construction material used by mankind and, at the
      same time, one of the most complex substances known in materials science. Since
      this mineral compound is highly porous, a better understanding of its surface
      chemistry, and in particular the reaction with water, is urgently required to
      understand and avoid corrosion of infrastructure like buildings and bridges. We
      have gained insight into proton transfer from concrete upon contact with water by
      applying the so-called Surface Science approach to a well-defined mineral,
      Wollastonite. Data from IR (infrared) spectroscopy reveal that exposure of this
      calcium-silicate (CS) substrate to H2 O leads to dissociation and the formation
      of OH-species. This proton transfer is a chemical reaction of key importance,
      since on the one hand it triggers the conversion of cement into concrete (a
      calcium-silicate-hydrate phase), but on the other hand also governs the corrosion
      of concrete. Interestingly, we find that no proton transfer takes place when the
      same surface is exposed to methanol. In order to understand this unexpected
      difference, the analysis of the spectroscopic data obtained was aided by a
      detailed, first-principles computational study employing density functional
      theory (DFT). The combined experimental and theoretical effort allows derivation
      of a consistent picture of proton transfer reactions occurring in CS and CSH
      phases. Implications for strategies to protect this backbone of urban
      infrastructure from corrosion in harsh, aqueous environments will be discussed.

PMID- 29644730
TI  - In vitro quality of apheresis platelets divided into paediatric-sized units and
      stored in PVC bags plasticised with TOTM, BTHC or DINCH.
AB  - BACKGROUND AND OBJECTIVES: Two of the predictive factors of the quality of small
      volumes of platelets suitable for paediatric use are bag size and material. This
      study evaluated the storage properties of paediatric platelet aliquots in TOTM-,
      BTHC- or DINCH-PVC bags. METHODS/MATERIALS: (i) Three apheresis platelet
      concentrates (PC) were pooled and split into three units. One was retained as an
      adult unit (control; polyolefin bag). The second and third units were split into
      four MacoPharma TOTM-PVC and BTHC-PVC paediatric bags, respectively. (ii) Two
      apheresis PC were pooled and split into two units. One PC was retained as an
      adult unit, and the other was split into four Fresenius DINCH-PVC paediatric
      bags. Testing was performed on storage for pH, blood gases, hypotonic shock
      response, soluble CD62P, LDH, glucose and lactate, ATP, CD62P, CD63, platelet
      derived microparticles and annexin V. RESULTS: The volumes, platelet yields and
      pH of all paediatric units met local specifications. The TOTM-PVC bag showed no
      worse quality than the adult bag up to day 7 for all parameters studied, and it
      maintained pH higher than BTHC-PVC and DINCH-PVC over storage. The BTHC-PVC bag
      was shown to be the most gas permeable; however, it had the highest glucose
      consumption rates and the highest platelet activation. CONCLUSION: All bags
      showed an acceptable in vitro quality. Overall, the TOTM-PVC paediatric bag
      showed better platelet quality compared to the other storage bags, whereas
      storage in the BTHC-PVC bag resulted in poorer platelet quality.

PMID- 29644732
TI  - Editorial: patient-reported outcomes in chronic HCV-a PROMISing approach to an
      ongoing problem. Authors' reply.

PMID- 29644731
TI  - Editorial: alleviating the itch-the safety of rifampicin in the real world.

PMID- 29644733
TI  - Editorial: patient-reported outcomes in chronic HCV-a PROMISing approach to an
      ongoing problem.

PMID- 29644734
TI  - Editorial: the sphincter of Oddi strikes again-eluxadoline illuminates a
      controversial mechanism for the pathogenesis of acute pancreatitis.

PMID- 29644735
TI  - Editorial: optimal dose of carvedilol in portal hypertension...nearly there.
      Authors' reply.

PMID- 29644736
TI  - Editorial: are the "miraculous" direct-acting antiviral (DAA) regimens really
      safe?

PMID- 29644737
TI  - Editorial: optimal dose of carvedilol in portal hypertension...nearly there.

PMID- 29644738
TI  - Editorial: the prevalence of Helicobacter pylori infection worldwide-knowns and
      unknowns. Authors' reply.

PMID- 29644739
TI  - Editorial: monitoring vedolizumab trough serum concentration in inflammatory
      bowel disease-following the fate of anti-TNF-alpha agents?

PMID- 29644740
TI  - Editorial: isolated duodenal eosinophilia-clinical condition or just seeing
      spots?

PMID- 29644741
TI  - Editorial: symptom association probability during reflux testing-what is the
      gain?

PMID- 29644742
TI  - Editorial: ways to reduce emergency department utilisation among IBD patients.

PMID- 29644743
TI  - Letter: infliximab concentrations during induction therapy-one size does not fit
      all.

PMID- 29644744
TI  - Editorial: the prevalence of Helicobacter pylori infection worldwide-knowns and
      unknowns.

PMID- 29644745
TI  - Editorial: vancomycin - a promising option for the treatment of primary
      sclerosing cholangitis?

PMID- 29644746
TI  - The distinct PhoPR mediated responses to phosphate limitation in Bacillus
      subtilis subspecies subtilis and spizizenii stem from differences in wall
      teichoic acid composition and metabolism.
AB  - The PhoPR-mediated response to phosphate limitation (PHO response) in Bacillus
      subtilis subsp subtilis is amplified and maintained by reducing the level of
      Lipid VG composed of poly(glycerol phosphate), a wall teichoic acid (WTA)
      biosynthetic intermediate that inhibits PhoR autokinase activity. However, the
      reduction in Lipid VG level is effected by activated PhoP~P, raising the question
      of how the PHO response is first initiated. Furthermore, that WTA is composed of
      poly(ribitol phosphate) in Bacillus subtilis subsp spizizenii prompted an
      investigation of how the PHO response is regulated in that bacterium. We report
      that the PHO responses of B. subtilis subsp subtilis and subsp spizizenii are
      distinct. The PhoR kinases of the two B. subtilis subspecies are functionally
      equivalent and are activated either by the TagA/TarA or TagB/TarB enzyme product.
      However, they are inhibited by Lipid VG composed of poly(glycerol phosphate) but
      not by Lipid VR composed of poly(ribitol phosphate). Therefore, the distinctive
      PHO responses of these B. subtilis subspecies stem from the differential
      sensitivity of PhoR kinases to the polyol composition of Lipid V and from the
      genomic organization of WTA biosynthetic genes and the regulation of their
      expression.

PMID- 29644747
TI  - Multidentate Phosphanyl Phosphinines: Synthesis and Properties.
AB  - With respect to the well-developed chemistry of pyridines, that of phosphinines
      is in its infancy. There are still challenges to be overcome with respect to the
      development of simple syntheses and the application of phosphinine derivatives.
      Here, we show that sodium phosphinin-2-olate is a valuable building block to
      prepare multidentate phosphinine ligands, which in turn can be employed for the
      preparation of metal complexes. These PdII and RhI complexes were fully
      characterized, including by NMR spectra and single-crystal X-ray diffraction
      studies, which clearly demonstrate that molecules R3-x P(O-phosphinine)x with
      one, two, and three phosphinines (x=1, 2, 3) can be tethered to a central
      phosphorus donor center to give bis-, tris-, and tetradentate ligands.

PMID- 29644749
TI  - EQUIPTMOD as a basis for rational investment decisions in tobacco control.

PMID- 29644748
TI  - Amidated Scolopin-2 inhibits proliferation and induces apoptosis of Hela cells in
      vitro and in vivo.
AB  - This study aimed to investigate the effect of Scolopin-2, a cationic
      antimicrobial peptide from centipede venoms, and amidated Scolopin-2 on Hela cell
      viability in vitro and in vivo. The cellular proliferation was investigated with
      the MTT assay. Confocal laser scanning, flow cytometry, and Western blot analysis
      were employed to localize Scolopin-2-NH2 in Hela cells and to study the caused
      cells apoptosis. We subcutaneously injected Hela cells into BALB/c nude mice and
      studied if Scolopin-2-NH2 suppressed tumor growth in the mice. Scolopin-2-NH2
      inhibited Hela proliferation in vitro in a dose-dependent manner with an IC50 of
      35 MUM. In addition, Scolopin-2-NH2 combined with mitochondria and regulated
      caspase-related apoptosis pathways in Hela cells. Scolopin-2-NH2 significantly
      suppressed tumor growth in the tumor-bearing mice without side effects, such as
      weight loss or abnormal changes in tissues, including liver, spleen, kidney, and
      lung. These results indicate Scolopin-2-NH2 may be a good therapeutic candidate
      for the treatment of Hela cervical cancer.

PMID- 29644750
TI  - Colchicine may be of therapeutic benefit in prurigo pigmentosa.
AB  - Prurigo pigmentosa (PP) is a rare inflammatory skin disease. Neutrophil-mediated
      inflammation is considered to be responsible for the etiopathogenesis of PP. We
      consider that colchicine may be an effective agent in the treatment of PP since
      it exerts an antiinflammatory effect by inhibiting neutrophil chemotaxis. Further
      studies are required to verify whether colchicine is an effective treatment
      option for PP.

PMID- 29644751
TI  - Disease Modification in Parkinson's Disease: Current Approaches, Challenges, and
      Future Considerations.
AB  - The greatest unmet therapeutic need in Parkinson's disease is the development of
      treatment that slows the relentless progression of the neurodegenerative process.
      The concept of "disease modification" encompasses intervention types ranging from
      those designed to slow the underlying degeneration to treatments directed at
      regenerating or replacing lost neurons. To date all attempts to develop effective
      disease-modifying therapy have failed. Many reasons have been proposed for these
      failures including our rudimentary understanding of disease pathogenesis and the
      assumption that each targeted mechanisms of disease apply to most patients with
      the same clinical diagnosis. Here we review all aspects of this broad field
      including general concepts and past challenges followed by a discussion of
      treatment approaches under the following 4 categories: (1) alpha-synuclein, (2)
      pathogenic mechanisms distinct from alpha-synuclein (most also potentially
      triggered by alpha-synuclein toxicity), (3) non-SNCA genetic subtypes of "PD,"
      and (4) possible disease-modifying interventions not directly influencing the
      underlying PD pathobiology. We emphasize treatments that are currently under
      active clinical development and highlight a wide range of important outstanding
      questions and concerns that will need to be considered to advance the field of
      disease modification in PD. Critically, it is unknown whether the dysfunctional
      molecular pathways/organelles amenable to modification occur in a sequential
      fashion across most clinically affected individuals or manifest differentially in
      independent molecular subtypes of PD. It is possible that there is no "order of
      disruption" applicable to most patients but, rather, "type of disruption"
      applicable to subtypes dependent on unknown factors, including genetic
      variability and other causes for heterogeneity in PD. Knowing when (early vs
      late), which (eg, synaptic transmission, endosomal sorting and maturation,
      lysosomal degradation, mitochondrial biogenesis), and in whom (PD subtype)
      specific disrupted cell pathways are truly pathogenic versus compensatory or even
      protective, will be important in considering the use of single or combined
      ("cocktails") putative disease-modifying therapies to selectively target these
      processes. Beyond the current phase 2 or 3 studies underway evaluating treatments
      directed at oxidative stress (inosine), cytosolic Ca2+ (isradipine), iron
      (deferiprone), and extracellular alpha-synuclein (passive immunization), and
      upcoming trials of interventions affecting c-Abl, glucagon-like peptide-1, and
      glucocerebrosidase, it might be argued that further trials in populations not
      enriched for the targeted pathogenic process are doomed to repeat the failures of
      the past. (c) 2018 International Parkinson and Movement Disorder Society.

PMID- 29644752
TI  - Studies on the local structures for the trigonal Ni3+ centers in cathode
      materials LiAly Co1-y O2 (y = 0, 0.1, 0.5, and 0.8).
AB  - The local angular distortions Deltatheta are theoretically studied for the
      various Ni3+ centers in LiAly Co1-y O2 at different Al concentrations (y = 0,
      0.1, 0.5, and 0.8) based on the perturbation calculations of electron
      paramagnetic resonance g factors for a trigonally distorted octahedral 3d7
      cluster with low spin (S = 1/2). Due to the Jahn-Teller effect, the [NiO6 ]9-
      clusters are found to experience the local angular distortions (Deltatheta ~ 5
      degrees -9 degrees ) along the C3 axis. The variation trend of Deltatheta with y
      is in accordance with that of anisotropy (Deltag = g||  - g? ). As the
      substitutions can weaken bond strengths between transition metal and oxygen and
      the structural stability plays an important role in cathode performances,
      detailed investigations on the structural properties of the cathode materials
      LiAly Co1-y O2 can be practically helpful to understand the performances of these
      materials. The oxy-redox properties of LiAly Co1-y O2 systems are comprehensible
      in the framework of Ni3+ /Ni4+ couples, and the trigonally compressed octahedral
      [NiO6 ]9- clusters are applicable to the clarification of the electrochemical
      properties of lithium nickel oxide batteries. It appears that LiAl0.8 Co0.2 O2
      with the largest Al concentration may correspond to the smallest distortion among
      the mixing systems.

PMID- 29644753
TI  - Editorial: Why should we use bivalirudin today?

PMID- 29644755
TI  - Off-label utilization of monorail balloon catheters.

PMID- 29644754
TI  - Editorial: Percutaneous pulmonary valve implantation: Better technology is on the
      way!

PMID- 29644756
TI  - Quetiapine for Parkinson's Disease psychosis: Evidence-based medicine versus
      expert belief: A case study.

PMID- 29644757
TI  - Does deep brain stimulation of the subthalamic nucleus prolong survival in
      Parkinson's Disease?

PMID- 29644758
TI  - Peripherally Cyanated Subphthalocyanines as Potential n-Type Organic
      Semiconductors.
AB  - A series of peripherally dicyano-, tricyano-, and tetracyano-substituted
      subphthalocyanines (SubPcs) have been prepared through microwave-assisted,
      palladium-mediated cyanation of iodinated precursors. The introduction of pi
      accepting cyano groups in the macrocycle clearly influences its electronic and
      redox properties, which are dependent on the number and relative position of
      these substituents. Additional functionalization of the periphery of SubPcs with
      electron-donating or -withdrawing groups allows for a further fine-tuning of
      their features, leading to intensely absorbing, strongly electron-accepting
      panchromatic dyes with low-lying LUMO energy levels. Flash-photolysis time
      resolved microwave conductivity measurements on vapor-deposited films demonstrate
      that some of these novel SubPc derivatives display remarkable intrinsic charge
      carrier mobilities that are comparable to or larger than those of other known
      well-performing acceptor SubPcs; thus confirming their potential as n-type
      organic semiconductors for application in the fabrication of photovoltaic
      devices.

PMID- 29644759
TI  - Strategies associated with low-risk drinking: a population-based study.
AB  - OBJECTIVE: To examine the relative frequency of use of seven strategies to
      moderate drinking (SMD) among low-risk and risky drinkers. METHODS: Cross
      sectional data from the 2013 National Drug Strategy Household Survey was used.
      The analytical sample included 11,462 Australians aged 18-64 who had consumed
      alcohol in the previous year. Logistic regression was used. RESULTS: Analyses
      indicated a curvilinear relationship between use of SMD and alcohol consumption.
      Across the seven SMD, constant use of a strategy, compared with never using a
      strategy, was associated with low-risk drinking. Never using a strategy, compared
      with using one rarely, was also associated with low-risk drinking. When used
      occasionally, strategies that implied less alcohol consumed per hour (e.g. refuse
      unwanted drinks) increased the likelihood of low-risk drinking, whereas less
      direct strategies (e.g. counting drinks) increased the likelihood of risky
      drinking. CONCLUSIONS: Adult Australians who drink at low levels use a range of
      strategies to moderate their alcohol consumption. Overall, consistent use of one
      or more SMD was associated with low-risk drinking patterns. IMPLICATIONS: Public
      health responses to risky drinking may be enhanced by promoting the consistent
      use of SMD as a way to reduce overall alcohol consumption.

PMID- 29644760
TI  - Housing conditions associated with recurrent gastrointestinal infection in urban
      Aboriginal children in NSW, Australia: findings from SEARCH.
AB  - OBJECTIVE: To examine the associations between housing and gastrointestinal
      infection in Aboriginal children in urban New South Wales. METHODS: A total of
      1,398 Aboriginal children were recruited through four Aboriginal Community
      Controlled Health Services. Multilevel regression modelling of survey data
      estimated associations between housing conditions and recurrent gastrointestinal
      infection, adjusting for sociodemographic and health factors. RESULTS: Of the
      sample, 157 children (11%) had recurrent gastrointestinal infection ever and 37
      (2.7%) required treatment for recurrent gastrointestinal infection in the past
      month. Children in homes with 3+ housing problems were 2.51 (95% CrI 1.10, 2.49)
      times as likely to have recurrent gastrointestinal infection ever and 6.79 (95%
      CrI 2.11, 30.17) times as likely to have received recent treatment for it (versus
      0-2 problems). For every additional housing problem, the prevalence of recurrent
      gastrointestinal infection ever increased by a factor of 1.28 (95% CrI 1.14,
      1.47) and the prevalence of receiving treatment for gastrointestinal infection in
      the past month increased by a factor of 1.64 (95% CrI 1.20, 2.48). CONCLUSIONS:
      Housing problems were independently associated with recurrent gastrointestinal
      infection in a dose-dependent manner. Implications for public health: The role of
      housing as a potential determinant of health in urban Aboriginal children merits
      further attention in research and policy settings.

PMID- 29644761
TI  - A General One-Pot Synthesis of 2H-Indazoles Using an Organophosphorus-Silane
      System.
AB  - A simple and direct approach for the regioselective construction of the
      privileged 2H-indazole scaffold is described. The developed one-pot strategy
      involves phospholene-mediated N-N bond formation to access 2H-indazoles. The
      amount of organophosphorus reagent was minimized by recycling the phospholene
      oxide with organosilane reductants. Starting from functionalized 2
      nitrobenzaldehydes and primary amines, a mild reductive cyclization, involving
      the use of commercially available phospholene oxide and silanes, delivered a wide
      variety of substituted 2H-indazoles in good to excellent yields.

PMID- 29644762
TI  - An outbreak of Q fever associated with parturient cat exposure at an animal
      refuge and veterinary clinic in southeast Queensland.
AB  - OBJECTIVE: To determine the source of a Q fever outbreak in humans at an animal
      refuge and veterinary clinic in southeast Queensland from October to December
      2016. METHODS: Case interviews and a retrospective cohort study of animal refuge
      and veterinary clinic staff using a self-administered questionnaire related to
      clinical history of Q fever, Q fever vaccination status and workplace activities
      during the exposure period. RESULTS: Seven cases (six confirmed, one probable)
      were identified. Forty-three questionnaires were completed (92% response rate).
      Workplace activities associated with the greatest risk of illness were the
      disposal of deceased cats or dogs (RR, 14.0; 95%CI, 1.9-104.1) and participating
      in euthanasia of cats or dogs (RR, 4.6; 95%CI, 1.3-16.9). Five feline birthing
      events occurred at the animal refuge from 25 September to 19 October 2016, each
      with subsequent euthanasia of the queen cat and litter. All cases had likely
      exposure to a specific queen cat and her litter that were euthanised the same day
      as the birthing event. CONCLUSIONS: A parturient cat was the most likely source
      of the outbreak. Implications for public health: Occupational groups and others
      with regular exposure to feline or canine parturient products should receive Q
      fever vaccine.

PMID- 29644763
TI  - Correlation of quality of life with risk factors for first-incident hip fracture
      in postmenopausal women.
AB  - AIM: The aim of this study was to identify the correlation between health-related
      quality of life (HRQOL) and risk factors of first-incidence hip fracture in
      postmenopausal women. METHODS: This case-control study included 99 postmenopausal
      women with first-incident hip fracture and 101 women without hip fracture who
      were matched according to age. Evaluation consisted of clinical factors, 36-item
      Short-Form Health Survey (SF-36) and dual-energy X-ray absorptiometry for bone
      mineral density of hip and spine. RESULTS: The mean age of patients with an
      accidental first-incident hip fracture was 78.0 years. Patients with hip
      fractures had significantly lower scores for SF-36 domains at enrollment and 4
      month follow up compared with the controls. Mental health also deteriorated
      significantly 4 months after hip fracture. Aside from lower HRQOL, clinical
      factors, including increased body height, no experience with estrogen therapy,
      rheumatoid arthritis, use of walking aids, less weight-bearing exercise, and
      diuretics use, were significant risk factors for hip fracture in univariate
      analysis. After multivariate adjustment, only the use of walking aids and
      decreased physical component summary were independent risk factors of hip
      fracture. Besides aging, use of walking aids, weight-bearing exercise, and
      psychological medication were the main factors affecting HRQOL when considering
      their relationship with hip fractures. CONCLUSION: The occurrence of first
      incidence hip fracture is highly associated with HRQOL. Aside from aging,
      clinical factors affecting HRQOL correlated with hip fracture incidence. Thus, in
      elderly women, exercise or physical therapy to improve physical function and
      mental support is crucial and should be considered the most important factors for
      first-incidence hip fracture prevention.

PMID- 29644764
TI  - Effect of simultaneously started clomiphene citrate and gonadotropins in
      antagonist regimes, on cumulative live births, fresh-cycle live births and cost
      of stimulation in IVF cycles.
AB  - AIM: The aim of the study was to compare simultaneously started clomiphene
      citrate (CC) and gonadotropins (Gn) with gonadotropins alone in conventional
      antagonist regimes with respect to fresh-cycle live births, cumulative live
      births and cost of ovarian stimulation per started cycle. METHODS: This was a
      single-center prospective cohort study conducted over 1 year. Women undergoing
      autologous in vitro fertilization (IVF) treatment in antagonist protocols and who
      consented to participate in the study were divided into two cohorts. The CC
      cohort (n = 86) received 50 mg CC for 5 days and individualized Gn daily until
      the hCG trigger, both starting from day 2 and antagonist daily from day 8 of
      menstrual cycle. The Gn-only cohort (n = 349) received individualized Gn from day
      2 and the antagonist from day 7 of menstrual cycle. IVF outcomes and cost of
      stimulation were compared between two cohorts across expected ovarian response
      categories. RESULTS: The CC cohort used a mean lower dose of Gn (1741.38 +/-
      604.46 vs 1980.54 +/- 686.42; MD = -239.16; 95%CI = -348.03 to -189.24; P =
      0.003) over fewer days (8.54 +/- 1.86 vs 9.25 +/- 1.97; MD =-0.71;95% CI = -1.17
      to -0.25; P = 0.0026) to achieve similar retrieved oocytes, (9.19 +/- 5.92 vs
      9.36 +/- 6.96; MD = -0.17; 95%CI -1.77 to + 1.43; P = 0.83), positive bhCG rates
      (40% vs 29.6%, MD = 10.4%; OR = 1.65, 95%CI = 0.95-2.86; P = 0.078) and live
      births in fresh cycles (32.31% vs 21.30%; MD = 11.01%; OR = 1.76; 95%CI = 0.97
      3.19; P = 0.06) and cumulative live births per initiated cycle (30.23% vs 20.34%;
      MD = 9.89%; OR = 1.697; 95%CI = 0.99-2.88; P = 0.0501). The dose lowering
      achieved a 28-40% reduction in the cost of stimulation, which was most noticeable
      in the hyper-responder category for both hMG cycles, (Rs.11 602.3 +/- 3365.9 vs
      19615 +/- 2677.1; MD = -8012.7; %age reduction: 40.8%; P = 0.0007) and
      recombinant FSH cycles (Rs. 22 459.6 +/- 6255.3 vs 33 022.1 +/- 9891.2; MD: -10
      562; %age reduction: -32%; P = 0.0001). CONCLUSION: CC started simultaneously
      with Gn in antagonist regimes helps lower the cost of stimulation without
      affecting IVF outcomes.

PMID- 29644765
TI  - Correlation between novel 3D high-resolution manometry esophagogastric junction
      metrics and pH-metry in reflux disease patients.
AB  - BACKGROUND AND AIMS: We recently developed 2 novel 3D high-resolution manometry
      (HRM) metrics of esophagogastric junction (EGJ) contractility to differentiate
      the lower esophageal sphincter (LES) and crural diaphragm (CD) elements of EGJ
      pressure. This study aimed to compare these metrics to the EGJ-contractile
      integral (EGJ-CI) and to analyze their correlation with esophageal acid exposure
      time (AET) on pH-metry. METHODS: Thirty-one gastro-oesophageal reflux disease
      (GERD) patients and 20 control subjects underwent 24-hour pH-metry and HRM using
      a 3D-HRM catheter. EGJ metrics were calculated during 3 consecutive respiratory
      cycles at rest. The EGJ-CI was calculated using the DCI tool in the ManoView
      software. 3D LES pressure (3D-LESP) and 3D-DHA, a metric quantifying the CD
      component of the 3D-HRM pressure topography, were calculated using a MATLAB
      program. Pearson correlation was used to calculate correlations with AET. KEY
      RESULTS: 3D-LESP, 3D-DHA, and EGJ-CI were all significantly lower in GERD
      patients than in control subjects (P < .05) and all were significantly correlated
      with AET (R = -.48, -.42, -.52, respectively, all P < .01). The 3D-DHA and EGJ-CI
      also strongly correlated with each other (R = .84, P < .001). CONCLUSIONS &
      INFERENCES: Both 3D-EGJ metrics were correlated with AET emphasizing the
      importance of both LES and CD function as a determinant of EGJ competence. 3D-DHA
      also strongly correlated with the EGJ-CI suggesting that EGJ-CI is strongly
      driven by the asymmetrical CD pressure component.

PMID- 29644766
TI  - Fear of recurrence among older breast, ovarian, endometrial, and colorectal
      cancer survivors: Findings from the WHI LILAC study.
AB  - OBJECTIVE: To examine the prevalence of and factors associated with fear of
      recurrence (FCR) following treatment for breast, ovarian, endometrial, and
      colorectal cancer among older women. METHODS: Participants were enrolled in the
      Women's Health Initiative Life and Longevity After Cancer study. Descriptive
      statistics and multivariate logistic regression models were used to assess the
      association of demographic, clinical, and quality of life variables with
      survivors' FCR, dichotomized as <14 (low) or >=14 (high) using the Cancer Worry
      Scale. RESULTS: Out of the 4259 participants, 3124 (73.3%) were diagnosed with
      breast cancer, 559 (13.1%) with colorectal cancer, 493 (11.6%) with endometrial
      cancer, and 83 (2%) with ovarian cancer. There were no significant differences in
      FCR by cancer type (P = .75), with a mean scale score of 10.8 +/- 2.87 for all
      participants combined. Approximately 16% (n = 679) were in the high FCR group.
      Multivariable analyses indicated that being younger at diagnosis, reporting a
      symptom score of >=8, receipt of chemotherapy, and lower self-rated health were
      significantly associated with high FCR. Women who were widowed or never married
      were less likely to report high FCR. CONCLUSIONS: Fear of recurrence was
      experienced by a small but important proportion of older, long-term cancer
      survivors and is associated with multiple demographic and clinical variables.
      These results will better inform researchers and clinicians regarding the
      individuals who are at risk of FCR.

PMID- 29644767
TI  - Heavy Carbene Analogues: Donor-Free Bismuthenium and Stibenium Ions.
AB  - Kinetically stabilized congeners of carbenes, R2 C, possessing six valence
      electrons (four bonding electrons and two non-bonding electrons) have been
      restricted to Group 14 elements, R2 E (E=Si, Ge, Sn, Pb; R=alkyl or aryl) whereas
      isoelectronic Group 15 cations, divalent species of type [R2 E]+ (E=P, As, Sb,
      Bi; R=alkyl or aryl), were unknown. Herein, we report the first two examples,
      namely the bismuthenium ion [(2,6-Mes2 C6 H3 )2 Bi][BArF4 ] (1; Mes=2,4,6-Me3 C6
      H2 , ArF =3,5-(CF3 )2 C6 H3 ) and the stibenium ion [(2,6-Mes2 C6 H3 )2 Sb][B(C6
      F5 )4 ] (2), which were obtained by using a combination of bulky meta-terphenyl
      substituents and weakly coordinating anions.

PMID- 29644768
TI  - MLCK-mediated intestinal permeability promotes immune activation and visceral
      hypersensitivity in PI-IBS mice.
AB  - BACKGROUND: Alterations in intestinal permeability regulated by tight junctions
      (TJs) are associated with immune activation and visceral hypersensitivity in
      irritable bowel syndrome (IBS). Myosin light chain kinase (MLCK) is an important
      mediator of epithelial TJ. The aim of this study is to investigate the role of
      MLCK in the pathogenesis of IBS using a post infectious IBS (PI-IBS) mouse model.
      METHODS: Trichinella spiralis-infected PI-IBS mouse model was used. Urine
      lactulose/mannitol ratio was measured to assess intestinal epithelial
      permeability. Western blotting was used to evaluate intestinal TJ protein (zonula
      occludens-1) and MLCK-associated protein expressions. Immune profile was assessed
      by measuring Th (T helper) 1/Th2 cytokine expression. Visceral sensitivity was
      determined by abdominal withdrawal reflex in response to colorectal distension.
      RESULTS: Eight weeks after inoculation with T. spiralis, PI-IBS mice developed
      decreased pain and volume thresholds during colorectal distention, increased
      urine lactulose/mannitol ratio, elevated colonic Th1/Th2 cytokine ratio, and
      decreased zonula occludens-1 expression compared to the control mice. MLCK
      expression was dramatically elevated in the colonic mucosa of PI-IBS mice
      compared to the control mice, alongside increased pMLC/MLC and decreased MLCP
      expression. Administration of MLCK inhibitor and TJ blocker both reversed the
      increased intestinal permeability, visceral hypersensitivity, and Th1-dominant
      immune profile in PI-IBS mice. CONCLUSION: MLCK is a pivotal step in inducing
      increased intestinal permeability promoting low-grade intestinal immune
      activation and visceral hypersensitivity in PI-IBS mice. MLCK inhibitor may
      provide a potential therapeutic option in the treatment of IBS.

PMID- 29644769
TI  - Reactive Chemical Probes: Beyond the Kinase Cysteinome.
AB  - The reaction of small-molecule chemical probes with proteins has been harnessed
      to develop covalent inhibitor drugs and protein-profiling technologies. This
      Essay discusses some of the recent enhancements to the chemical biology toolkit
      that are enabling the study of previously unchartered areas of chemoproteomic
      space. An analysis of the kinome is used to illustrate the potential for these
      approaches enable the pursuit of new targets using reactive chemical probes.

PMID- 29644770
TI  - TMEM55B contributes to lysosomal homeostasis and amino acid-induced mTORC1
      activation.
AB  - Mammalian/mechanistic target of rapamycin complex 1 (mTORC1) responds to growth
      factors and nutrient availability. Amino acids induce the recruitment of mTORC1
      to the lysosomal membrane and its consequent activation, but the molecular
      mechanism of such activation has remained unclear. We have now examined the role
      of TMEM55B, a lysosomal protein of unknown molecular function, in this process on
      the basis of the results of proteomics and immunofluorescence analyses showing
      that TMEM55B interacts with many proteins that participate in mTORC1 activation
      including components of the vacuolar-type proton ATPase (V-ATPase) and Ragulator
      complexes at the lysosomal membrane. The amino acid-induced phosphorylation of
      the mTORC1 substrates S6K and 4E-BP was attenuated in TMEM55B-depleted cells
      compared with control cells. Depletion of TMEM55B was also found to evoke
      lysosomal stress as showed by translocation of the transcription factor TFEB to
      the nucleus. Furthermore, recruitment of the V1 domain subcomplex of V-ATPase to
      lipid rafts was abrogated in TMEM55B-depleted cells. Collectively, our results
      suggest that TMEM55B contributes to assembly of the V-ATPase complex in lipid
      rafts of the lysosomal membrane and to subsequent activation of mTORC1.

PMID- 29644771
TI  - Complexing DNA Origami Frameworks through Sequential Self-Assembly Based on
      Directed Docking.
AB  - Ordered DNA origami arrays have the potential to compartmentalize space into
      distinct periodic domains that can incorporate a variety of nanoscale objects.
      Herein, we used the cavities of a preassembled 2D DNA origami framework to
      incorporate square-shaped DNA origami structures (SQ-origamis). The framework was
      self-assembled on a lipid bilayer membrane from cross-shaped DNA origami
      structures (CR-origamis) and subsequently exposed to the SQ-origamis. High-speed
      AFM revealed the dynamic adsorption/desorption behavior of the SQ-origamis, which
      resulted in continuous changing of their arrangements in the framework. These
      dynamic SQ-origamis were trapped in the cavities by increasing the Mg2+
      concentration or by introducing sticky-ended cohesions between extended staples,
      both from the SQ- and CR-origamis, which enabled the directed docking of the SQ
      origamis. Our study offers a platform to create supramolecular structures or
      systems consisting of multiple DNA origami components.

PMID- 29644772
TI  - (2R,5S)-Theaspirane Identified as the Kairomone for the Banana Weevil,
      Cosmopolites sordidus, from Attractive Senesced Leaves of the Host Banana, Musa
      spp.
AB  - The principal active component produced by highly attractive senesced host banana
      leaves, Musa spp., for the banana weevil, Cosmopolites sordidus, is shown by
      coupled gas chromatography-electroantennography (GC-EAG), coupled GC-mass
      spectrometry (GC-MS), chemical synthesis and coupled enantioselective (chiral) GC
      EAG to be (2R,5S)-theaspirane. In laboratory behaviour tests, the synthetic
      compound is as attractive as natural host leaf material and presents a new
      opportunity for pest control.

PMID- 29644773
TI  - Highly Efficient Supramolecular Catalysis by Endowing the Reaction Intermediate
      with Adaptive Reactivity.
AB  - A new strategy of highly efficient supramolecular catalysis is developed by
      endowing the reaction intermediate with adaptive reactivity. The supramolecular
      catalyst, prepared by host-guest complexation between 2,2,6,6
      tetramethylpiperidin-1-oxyl (TEMPO) and cucurbit[7]uril (CB[7]), was used for
      biphasic oxidation of alcohols. Cationic TEMPO+ , the key intermediate, was
      stabilized by the electrostatic effect of CB[7] in aqueous phase, thus promoting
      the formation of TEMPO+ and inhibiting side reactions. Moreover, through the
      migration into the organic phase, TEMPO+ was separated from CB[7] and recovered
      the high reactivity to drive a fast oxidation of substrates. The adaptive
      reactivity of TEMPO+ induced an integral optimization of the catalytic cycle and
      greatly improved the conversion of the reaction. This work highlights the unique
      advantages of dynamic noncovalent interactions on modulating the activity of
      reaction intermediates, which may open new horizons for supramolecular catalysis.

PMID- 29644774
TI  - Preparation of Cyclobutene Acetals and Tricyclic Oxetanes through Photochemical
      Tandem and Cascade Reactions.
AB  - We describe a photochemical reaction using two starting materials, a cyclopent-2
      enone and an alkene, which are transformed in a controlled manner via the initial
      [2+2]-photocycloaddition adducts into cyclobutene aldehydes (conveniently trapped
      as stable acetals) or unprecedented angular tricyclic 4:4:4 oxetane-containing
      skeletons. These compounds are formed through tandem or triple cascade
      photochemical reaction processes, respectively. Small libraries of each compound
      class were prepared, thus suggesting that this photochemistry approach opens new
      opportunities for synthesis design and for widening molecular diversity.

PMID- 29644775
TI  - Exploring the combination of SSKI and topical heparin in a case of erythema
      nodosum migrans.
AB  - Erythema nodosum migrans (subacute nodular migratory panniculitis) is an uncommon
      type of panniculitis characterized by migrating subcutaneous nodules or plaque on
      the lower extremity. There are a very few cases of Erythema nodosum migrans
      reported and thus its appropriate treatment modality is not defined. We describe
      a case of a 30-year-old male with idiopathic erythema nodosum migrans which was
      manifest centrifugally spreading, slightly morpheaform erythematous plaque on the
      lower left leg. The patient was diagnosed initially and treated as a case of
      furunculosis with poor clinical response. The skin biopsy showed features
      consistent with subacute nodular panniculitis. Saturated Solution of Potassium
      Iodide along with topical Heparin successfully treated the patient, when the
      conventional treatment modalities failed. In a morpheaform centrifugally expanded
      plaque, erythema nodosum migrans should be kept in mind in the differential
      diagnosis, especially in the lower extremities in cases of unknown etiology.

PMID- 29644776
TI  - Constructing whole of population cohorts for health and social research using the
      New Zealand Integrated Data Infrastructure.
AB  - OBJECTIVES: To construct and compare a 2013 New Zealand population derived from
      Statistics New Zealand's Integrated Data Infrastructure (IDI) with the 2013
      census population and a 2013 Health Service Utilisation population, and to
      ascertain the differences in cardiovascular disease prevalence estimates derived
      from the three cohorts. METHODS: We constructed three national populations
      through multiple linked administrative data sources in the IDI and compared the
      three cohorts by age, gender, ethnicity, area-level deprivation and District
      Health Board. We also estimated cardiovascular disease prevalence based on
      hospitalisations using each of the populations as denominators. RESULTS: The IDI
      population was the largest and most informative cohort. The percentage
      differences between the IDI and the other two populations were largest for males
      and for those aged 15-34 years. The percentage differences between the IDI and
      Census cohorts were largest for people living in the most deprived areas. The
      ethnic distribution varied across the three cohorts. Using the IDI population as
      a reference, the Health Service Utilisation population generally overestimated
      cardiovascular disease prevalence, while the Census population generally
      underestimated it. CONCLUSIONS AND IMPLICATIONS: The New Zealand IDI population
      is the most comprehensive and appropriate national cohort for use in health and
      social research.

PMID- 29644777
TI  - The Cooperative Effect of Both Molecular and Supramolecular Chirality on Cell
      Adhesion.
AB  - Although helical nanofibrous structures have great influence on cell adhesion,
      the role played by chiral molecules in these structures on cells behavior has
      usually been ignored. The chirality of helical nanofibers is inverted by the odd
      even effect of methylene units from homochiral l-phenylalanine derivative during
      assembly. An increase in cell adhesion on left-handed nanofibers and weak
      influence of cell behaviors on right-handed nanofibers are observed, even though
      both were derived from l-phenylalanine derivatives. Weak and negative influences
      on cell behavior was also observed for left- and right-handed nanofibers derived
      from d-phenylalanine, respectively. The effect on cell adhesion of single chiral
      molecules and helical nanofibers may be mutually offset.

PMID- 29644778
TI  - High-Performance Sodium Metal Anodes Enabled by a Bifunctional Potassium Salt.
AB  - Developing Na metal anodes that can be deeply cycled with high efficiency for a
      long time is a prerequisite for rechargeable Na metal batteries to be practically
      useful despite their notable advantages in theoretical energy density and
      potential low cost. Their high chemical reactivity with the electrolyte and
      tendency for dendrite formation are two major issues limiting the reversibility
      of Na metal electrodes. In this work, we introduce for the first time potassium
      bis(trifluoromethylsulfonyl)imide (KTFSI) as a bifunctional electrolyte additive
      to stabilize Na metal electrodes, in which the TFSI- anions decompose into
      lithium nitride and oxynitrides to render a desirable solid electrolyte
      interphase layer while the K+ cations preferentially adsorb onto Na protrusions
      and provide electrostatic shielding to suppress dendritic deposition. Through the
      cooperation of the cations and anions, we have realized Na metal electrodes that
      can be deeply cycled at a capacity of 10 mAh cm-2 for hundreds of hours.

PMID- 29644779
TI  - Letter on "Pregnancy after bariatric surgery: Maternal and fetal outcomes of 39
      pregnancies and a literature review".

PMID- 29644780
TI  - Support needs of couples with hereditary breast and ovarian cancer during
      reproductive decision making.
AB  - OBJECTIVE: Reproductive decision making for couples with hereditary breast and
      ovarian cancer (HBOC) is complex and can result in decisional conflict or regret.
      This study investigated couples' support needs and aimed to identify vulnerable
      couples. Ultimately, we should strive to develop a clear standard of care
      guideline regarding reproductive decision support. METHODS: Mixed methods were
      used for data collection. A focus group study was conducted among 18 couples (N =
      35) with HBOC who had made a reproductive decision after reproductive
      counselling. Subsequently, 129 similar couples (N = 258) were invited to complete
      a cross-sectional survey based on the focus group study. RESULTS: Clinical and
      practical aspects of reproductive counselling were positively evaluated in the
      focus group study, although couples indicated a need for additional support with
      emotional and social concerns in which their relationship, social environment,
      and the way they picture their desired family were key elements. The survey was
      completed by 86 participants. Making a reproductive choice was experienced as
      (very) difficult by 43%, and 69% showed a need for additional support during
      decision making. Younger participants and those who opted for a natural pregnancy
      experienced more difficulty with reproductive decision making, and partners
      showed a higher need for psychological support than carriers. CONCLUSIONS:
      Couples with HBOC who need to make a reproductive decision have specific needs
      for guidance and support, of which the desired content and methods can vary. It
      is therefore important to identify vulnerable couples and to attune counselling
      to couples' needs.

PMID- 29644782
TI  - The value of health damage due to sulphur dioxide emissions from coal-fired
      electricity generation in NSW and implications for pollution licences.

PMID- 29644781
TI  - INPP4B overexpression and c-KIT downregulation in human achalasia.
AB  - BACKGROUND: Achalasia is a rare motility disorder characterized by myenteric
      neuron and interstitial cells of Cajal (ICC) abnormalities leading to
      deranged/absent peristalsis and lack of relaxation of the lower esophageal
      sphincter. The mechanisms contributing to neuronal and ICC changes in achalasia
      are only partially understood. Our goal was to identify novel molecular features
      occurring in patients with primary achalasia. METHODS: Esophageal full-thickness
      biopsies from 42 (22 females; age range: 16-82 years) clinically, radiologically,
      and manometrically characterized patients with primary achalasia were examined
      and compared to those obtained from 10 subjects (controls) undergoing surgery for
      uncomplicated esophageal cancer (or upper stomach disorders). Tissue RNA
      extracted from biopsies of cases and controls was used for library preparation
      and sequencing. Data analysis was performed with the "edgeR" option of R
      Bioconductor. Data were validated by real-time RT-PCR, western blotting and
      immunohistochemistry. KEY RESULTS: Quantitative transcriptome evaluation and
      cluster analysis revealed 111 differentially expressed genes, with a P <= 10-3 .
      Nine genes with a P <= 10-4 were further validated. CYR61, CTGF, c-KIT, DUSP5,
      EGR1 were downregulated, whereas AKAP6 and INPP4B were upregulated in patients vs
      controls. Compared to controls, immunohistochemical analysis revealed a clear
      increase in INPP4B, whereas c-KIT immunolabeling resulted downregulated. As
      INPP4B regulates Akt pathway, we used western blot to show that phospho-Akt was
      significantly reduced in achalasia patients vs controls. CONCLUSIONS &
      INFERENCES: The identification of altered gene expression, including INPP4B, a
      regulator of the Akt pathway, highlights novel signaling pathways involved in the
      neuronal and ICC changes underlying primary achalasia.

PMID- 29644783
TI  - Prevalence of mental disorders and psychosocial distress in German adolescent and
      young adult cancer patients (AYA).
AB  - OBJECTIVE: This study provides prevalence data of mental disorders (4-week, 1
      year, lifetime) and psychological distress in Adolescent and Young Adult (AYAs)
      with cancer. METHODS: We included an AYA subsample (15 to 39 year olds; diagnosed
      within the last 5 years) extracted from a larger sample (4.020 cancer patients)
      who had been recruited for an epidemiological study across all major tumor
      entities. Participants were assessed with a depression screener (PHQ-9).
      Following that, 50% of the participants who scored below the cutoff of 9 and all
      patients who scored above were assessed using the Composite International
      Diagnostic Interview for Oncology (CIDI-O). Patients also completed an anxiety
      screener (GAD-7). RESULTS: A total of 302 AYA (167 completed CIDI-O) were
      identified. With regard to psychological distress, 29.5% of the AYA had increased
      depression symptoms (PHQ-9), and 20.8% had increased anxiety symptoms (GAD-7).
      Gender and age were associated with psychological distress, with women and older
      AYA being found to have higher distress. The 4-week prevalence of mental
      disorders of any kind was 46.7% (95%-CI:39%-55%). Anxiety (24.4%; 95%-CI:20%-36%)
      and adjustment disorders (14.1%; 95%-CI:9%-19%) had the highest prevalence rates.
      The lowest prevalence rates were reported for alcohol dependence (0.8%; 95%-CI:0%
      2%) and somatoform disorders (3.7%; 95%-CI:1%-7%). The 1-year-prevalence was
      55.4% (CI:47.36-62.64), and the lifetime-prevalence was 69.5% (CI: 62.29-77.06).
      CONCLUSION: Our findings may sensitize clinicians to the possible presence of
      mental disorders in AYA. The results indicate that there is a strong need for
      psycho-oncological interventions designed to improve mental health in AYAs with
      cancer at all stages of medical care.

PMID- 29644784
TI  - MINDY1 Is a Downstream Target of the Polyamines and Promotes Embryonic Stem Cell
      Self-Renewal.
AB  - Embryonic stem cells have the ability to self-renew or differentiate and these
      processes are under tight control. We previously reported that the polyamine
      regulator AMD1 is critical for embryonic stem cell self-renewal. The polyamines
      putrescine, spermidine, and spermine are essential organic cations that play a
      role in a wide array of cellular processes. Here, we explore the essential role
      of the polyamines in the promotion of self-renewal and identify a new stem cell
      regulator that acts downstream of the polyamines: MINDY1. MINDY1 protein levels
      are high in embryonic stem cells (ESCs) and are dependent on high polyamine
      levels. Overexpression of MINDY1 can promote ESC self-renewal in the absence of
      the usually essential cytokine Leukemia Inhibitory Factor (LIF). MINDY1 protein
      is prenylated and this modification is required for its ability to promote self
      renewal. We go on to show that Mindy1 RNA is targeted for repression by mir-710
      during Neural Precursor cell differentiation. Taken together, these data
      demonstrate that high polyamine levels are required for ESC self-renewal and that
      they function, in part, through promotion of high MINDY1 levels. Stem Cells
      2018;36:1170-1178.

PMID- 29644785
TI  - Age and gender may be the key points in hyperglycemic patients with Helicobacter
      pylori infection combined colorectal adenoma-author's reply.

PMID- 29644786
TI  - Potential role of the pancreatic hormone insulin in resetting human peripheral
      clocks.
AB  - Mammalian circadian rhythms are phase-adjusted and amplified by external cues
      such as light and food. While the light input pathway via the central clock, the
      suprachiasmatic nucleus, has been well defined, the mechanism of feeding-induced
      circadian resetting remains undefined, particularly in humans. Animal studies
      have indicated that insulin, a pancreatic hormone that is secreted rapidly in
      response to feeding, is an input factor for a few peripheral clocks, such as
      liver and adipose tissue. In this study, using plucked and cultured hair
      follicles as a representative human peripheral clock, we examined the effect of
      insulin on circadian characteristics of clock gene expression. Our results
      demonstrate that insulin phase-shifts or amplifies the clock gene expression
      rhythms of ex vivo cultured hair follicles in a phase-responsive manner. To
      reduce the possibility that differences in species, genetic or environmental
      background, and experimental methods affected experimental outcomes, we also
      treated surgically extracted whisker follicles of Period2::Luciferase (Per2Luc )
      mice with insulin and found that the effect of insulin on clock gene expression
      was reproducible. These results suggest the possibility that feeding-induced
      insulin resets peripheral circadian clocks in humans.

PMID- 29644789
TI  - Construction of a Holliday Junction in Small Circular DNA Molecules for Stable
      Motifs and Two-Dimensional Lattices.
AB  - Design rules for DNA nanotechnology have been mostly learnt from using linear
      single-stranded (ss) DNA as the source material. For example, the core structure
      of a typical DAO (double crossover, antiparallel, odd half-turns) tile for
      assembling 2D lattices is constructed from only two linear ss-oligonucleotide
      scaffold strands, similar to two ropes making a square knot. Herein, a new type
      of coupled DAO (cDAO) tile and 2D lattices of small circular ss-oligonucleotides
      as scaffold strands and linear ss-oligonucleotides as staple strands are
      reported. A cDAO tile of cDAO-c64nt (c64nt: circular 64 nucleotides), shaped as a
      solid parallelogram, is constructed with a Holliday junction (HJ) at the center
      and two HJs at both poles of a c64nt; similarly, cDAO-c84nt, shaped as a crossed
      quadrilateral composed of two congruent triangles, is formed with a HJ at the
      center and four three-way junctions at the corners of a c84nt. Perfect 2D
      lattices were assembled from cDAO tiles: infinite nanostructures of nanoribbons,
      nanotubes, and nanorings, and finite nanostructures. The structural relationship
      between the visible lattices imaged by AFM and the corresponding invisible
      secondary and tertiary molecular structures of HJs, inclination angle of hydrogen
      bonds against the double-helix axis, and the chirality of the tile can be
      interpreted very well. This work could shed new light on DNA nanotechnology with
      unique circular tiles.

PMID- 29644787
TI  - Impact of the Make Healthy Normal mass media campaign (Phase 1) on knowledge,
      attitudes and behaviours: a cohort study.
AB  - OBJECTIVE: To determine the impact of the first phase of the Make Healthy Normal
      mass media campaign on NSW adults' active living and healthy eating knowledge,
      attitudes, intentions and behaviour. METHODS: Cohort design with NSW adults,
      followed up three times over 12 months, with n=939 participants completing all
      three waves. We used generalised linear mixed models to examine campaign
      awareness, knowledge, attitudes, intentions and behaviours over time. RESULTS:
      Campaign recognition built to a reasonable level (45% at Wave 3), although
      unprompted recall was low (9% at Wave 3). There were significant increases in
      knowledge of physical activity recommendations (46% to 50%), the health effects
      of obesity (52% to 64%), and weight loss benefits (53% to 65%), with stronger
      effects in campaign recognisers. Conversely, we found declines in self-efficacy
      and intention to increase physical activity (39% to 31%) and decrease soft drink
      consumption (31% to 24%). CONCLUSIONS: Overall, there are some positives for the
      campaign but intentions need to be a focus of future campaign phases. Continued
      investment over the medium- to long-term is needed. IMPLICATIONS: Mass media
      campaigns can play a role in obesity prevention but robust evaluations are needed
      to identify the characteristics of effective campaigns.

PMID- 29644788
TI  - High-intensity focused ultrasound treatment after cryolipolysis may be used to
      reduce pain: Two case report.
AB  - In recent years, interest in body sculpting has increased and various
      technologies have been used and developed. In the present study, we assessed the
      efficacy and safety of combination treatment using high-intensity focused
      ultrasound (HIFU) and cryolipolysis. The findings show that not only HIFU but
      also combination treatments are safe and well-tolerated options for the treatment
      of central abdominal subcutaneous adipose tissue (SAT). Interestingly, the pain
      associated with HIFU when it was performed after cryolipolysis was significantly
      reduced.

PMID- 29644790
TI  - Using chemiluminescence to determine whole blood antioxidant capacity in
      rheumatoid arthritis and Parkinson's disease patients.
AB  - The consequences of oxidative stress and inflammation are implicated in a wide
      range of diseases, including rheumatoid arthritis and Parkinson's disease. The
      status of antioxidant capacity in rheumatoid arthritis and Parkinson's disease
      remains unclear, in part due to common practice of assaying erythrocytes
      separately to plasma. This method removes any synergistic interactions between
      plasma and erythrocyte-based antioxidants. The experiments in this report tested
      antioxidant capacity in whole blood, erythrocytes and plasma by group and disease
      stage. Medically diagnosed patients were recruited along with appropriate control
      group participants. Fasting venous blood was assayed using chemiluminescence
      methods for: time to maximum light emitted, maximum light emitted, and plasma
      antioxidant capacity in vitamin E analogue units. Here we demonstrate that whole
      blood exhibits higher antioxidant capacity than either plasma or erythrocytes
      assayed separately. We report increased oxidative stress in the blood of
      rheumatoid arthritis patients by group (p = 0.018, p = 0.049). We show increased
      antioxidant capacity in Parkinson's disease patients by group (p < 0.001). For
      later stage Parkinson's disease patients, we report reduced oxidative stress (p =
      0.025), and increased antioxidant capacity and for erythrocytes (p < 0.001, p =
      0.004) and whole blood (p < 0.001, p = 0.003). Early stage Parkinson's disease
      showed higher antioxidant capacity on only one measure (p = 0.008). Whole blood
      chemiluminescence is a useful technique for determining redox status in disease
      and might help clarify the role of oxidative stress in rheumatoid arthritis and
      Parkinson's disease.

PMID- 29644791
TI  - Epigenome-Wide Association Study of Dietary Fiber Intake in African American
      Adolescents.
AB  - SCOPE: Low fiber intake is associated with increased risk for cardiovascular
      disease (CVD) and cancer. However, the underlying mechanisms are not well
      understood. Two hypotheses are tested: 1) dietary fiber would be associated with
      DNA methylation levels; 2) those DNA methylation changes would be associated with
      visceral adiposity and inflammation. Also the possibility that the associations
      between fiber and DNA methylation levels might be confounded with folic acid
      intake as sensitivity analysis are explored. METHODS AND RESULTS: An epigenome
      wide association study is conducted using Illumina 450K Bead-Chip on leukocyte
      DNA in 284 African American adolescents. Linear regression is performed to
      identify differentially methylated CpG sites associated with fiber. The
      methylation levels of 3 CpG sites (cg15200711, cg19462022, and cg07035602) in
      LPCAT1 and RASA3 genes are associated with fiber (false discovery rate [FDR] <
      0.05) after adjustment for covariates including folic acid. The methylation
      levels of cg07035602 and cg19462022 are also associated with visceral adiposity
      and inflammation. CONCLUSIONS: The data show that DNA methylation levels at
      LPCAT1 and RASA3 genes are associated with dietary fiber intake as well as with
      adiposity and inflammation. Future studies are warranted to determine whether
      epigenetic regulation may underlie the beneficial effects of fiber intake on
      adiposity and inflammation.

PMID- 29644792
TI  - Synthesis of 1,1'-Spirobiindane-7,7'-Disulfonic Acid and Disulfonimide:
      Application for Catalytic Asymmetric Aminalization.
AB  - 1,1'-Spirobiindane-7,7'-disulfonic acid (SPISA) and 1,1'-spirobiindane-7,7'
      disulfonimide were synthesized from 1,1'-spirobiindane-7,7'-diol (SPINOL) in 4
      steps using a Pd-catalyzed Newman-Kwart rearrangement as a key step. These new
      catalysts possessing a rigid spirocyclic backbone were evaluated in a catalytic
      asymmetric aminalization reaction, and SPISA/iPr2 NEt exhibited high
      enantioselectivity, demonstrating the utility of SPISA as a chiral Bronsted acid
      catalyst.

PMID- 29644793
TI  - Who does she think she is?

PMID- 29644794
TI  - An Oxidative Bioconjugation Strategy Targeted to a Genetically Encoded 5
      Hydroxytryptophan.
AB  - Approaches that enable the chemoselective, covalent modification of proteins in a
      site-specific manner have emerged as a powerful technology for a wide range of
      applications. The electron-rich unnatural amino acid 5-hydroxytryptophan was
      recently genetically encoded in both Escherichia coli and eukaryotes, thereby
      allowing its site-specific incorporation into virtually any recombinant protein.
      Herein, we report the chemoselective conjugation of various aromatic amines to
      full-length proteins under mild, oxidative conditions that target this site
      specifically incorporated 5-hydroxytryptophan residue.

PMID- 29644795
TI  - Mnemonic Institutions and Residential Clustering: Jewish Residential Patterns in
      Toronto.
AB  - In this paper, we envisage how the sociohistorical experiences of groups are
      related to their residential patterns. We posit that the residential clustering
      of a group can be strongly related to the group's mnemonic institutions, which
      are organizational symbols of collective identity that link the present to the
      past. We present the case of Jewish residential clustering patterns in Toronto to
      demonstrate our arguments. We employ 2001 Canadian Census tract-level data to
      show Jewish residential clustering patterns in relation to the presence of a
      synagogue or Jewish community center, the mnemonic institutions of Jews.

PMID- 29644796
TI  - Hematite Photoanode with Complex Nanoarchitecture Providing Tunable Gradient
      Doping and Low Onset Potential for Photoelectrochemical Water Splitting.
AB  - Over the past years, alpha-Fe2 O3 (hematite) has re-emerged as a promising
      photoanode material in photoelectrochemical (PEC) water splitting. In spite of
      considerable success in obtaining relatively high solar conversion efficiency,
      the main drawbacks hindering practical application of hematite are its
      intrinsically hampered charge transport and sluggish oxygen evolution reaction
      (OER) kinetics on the photoelectrode surface. In the present work, we report a
      strategy that synergistically addresses both of these critical limitations. Our
      approach is based on three key features that are applied simultaneously: i) a
      careful nanostructuring of the hematite photoanode in the form of nanorods, ii)
      doping of hematite by Sn4+ ions using a controlled gradient, and iii) surface
      decoration of hematite by a new class of layered double hydroxide (LDH) OER co
      catalysts based on Zn-Co LDH. All three interconnected forms of functionalization
      result in an extraordinary cathodic shift of the photocurrent onset potential by
      more than 300 mV and a PEC performance that reaches a photocurrent density of
      2.00 mA cm-2 at 1.50 V vs. the reversible hydrogen electrode.

PMID- 29644798
TI  - The Sociological Ethic and the Spirit of Power: Reflections on the Possibility of
      a Value-Neutrality and Its Consequences for Sociology.

PMID- 29644797
TI  - Altered gastrointestinal motility involving autoantibodies in the experimental
      autoimmune encephalomyelitis model of multiple sclerosis.
AB  - BACKGROUND: Multiple sclerosis (MS) is an autoimmune disease of the central
      nervous system that, in addition to motor, sensory, and cognitive symptoms, also
      causes constipation, which is poorly understood. Here, we characterize
      gastrointestinal (GI) dysmotility in the experimental autoimmune
      encephalomyelitis (EAE) mouse model of MS and evaluate whether autoantibodies
      target the enteric nervous system (ENS) and cause dysmotility. METHODS: EAE was
      induced in male SJL and B6 mice. GI motility was assessed in vivo and ex vivo in
      wild type (WT) and B cell-deficient mice. MS and EAE serum was used to survey
      potential targets in the ENS and changes in the ENS structure were characterized
      using immunohistochemistry. KEY RESULTS: EAE mice developed accelerated gastric
      emptying and delayed whole GI transit with reduced colonic motility. Fecal water
      content was reduced, and colonic migrating myoelectrical complexes (CMMC) and
      slow waves were less frequent. Colons from EAE mice exhibited decreased GFAP
      levels in glia. Sera from MS patients and from EAE mice targeted ENS neurons and
      glia. B-cell deficiency in EAE protected against colonic dysmotility. CONCLUSIONS
      & INFERENCES: Consistent with symptoms experienced in MS, we demonstrate that EAE
      mice widely exhibit features of GI dysmotility that persisted in the absence of
      extrinsic innervation, suggesting direct involvement of ENS neurocircuitry. The
      absence of GI dysmotility in B cell-deficient mice with EAE together with EAE and
      MS serum immunoreactivity against ENS targets suggests that MS could be
      classified among other diseases known to induce autoimmune GI dysmotility.

PMID- 29644799
TI  - Transparent Composites Made from Tunicate Cellulose Membranes and Environmentally
      Friendly Polyester.
AB  - A series of optically transparent composites were made by using tunicate
      cellulose membranes, in which the naturally organized cellulose microfibrillar
      network structure of tunicate tunics was preserved and used as the template and a
      solution of glycerol and citric acid at different molar ratios was used as the
      matrix. Polymerization through ester bond formation occurred at elevated
      temperatures without any catalyst, and water was released as the only byproduct.
      The obtained composites had a uniform and dense structure. Thus, the produced
      glycerol citrate polyester improved the transparency of the tunicate cellulose
      membrane while the cellulose membrane provided rigidity and strength to the
      prepared composite. The interaction between cellulose and polyester afforded the
      composites high thermal stability. Additionally, the composites were optically
      transparent and their shape, strength, and flexibility were adjustable by varying
      the formulation and reaction conditions. These composites of cellulose, glycerol,
      and citric acid are renewable and biocompatible and have many potential
      applications as structural materials in packaging, flexible displays, and solar
      cells.

PMID- 29644801
TI  - Exosomal MicroRNAs in Milk from Mothers Delivering Preterm Infants Survive in
      Vitro Digestion and Are Taken Up by Human Intestinal Cells.
AB  - SCOPE: This study investigates the ability of preterm milk exosomes to survive
      gastric/pancreatic digestion, internalization by intestinal epithelia, and the
      microRNAs (miRNAs) contents. METHODS AND RESULTS: At average infant age 1 week
      and 6 days, milk is collected from mothers who delivered preterm and term infants
      (n = 10). Milk is exposed to conditions simulating infant gut digestion. Exosomes
      are isolated and lysed, and the exposed miRNAs are sequenced. Preterm milk
      exosomes survive in vitro digestion, and can be taken up by intestinal epithelia.
      Three hundred and thirty miRNAs are identified as preterm milk exosome miRNAs,
      and in vitro digestion does not have a pronounced effect on their expression. The
      abundant miRNAs in preterm milk exosomes are similar to those from term milk.
      Twenty-one low abundance miRNAs are specifically expressed in preterm milk
      exosomes compared to early term milk in the current study and what previously is
      found in mature term milk. CONCLUSION: These results for the first time reveal
      the survivability of preterm milk exosomes following simulated gastric/pancreatic
      digestion. The authors demonstrate the richness of the miRNAs content in these
      exosomes. The results improve the knowledge of preterm milk biology and the
      molecular basis by which exosome miRNAs may uniquely affect preterm infants
      during early development.

PMID- 29644802
TI  - Divergent Total Syntheses of Enmein-Type Natural Products: (-)-Enmein, (-)
      Isodocarpin, and (-)-Sculponin R.
AB  - Divergent total syntheses of the enmein-type natural products (-)-enmein, (-)
      isodocarpin, and (-)-sculponin R have been achieved in a concise fashion. Key
      features of the strategy include 1) an efficient early-stage cage formation to
      control succeeding diastereoselectivity, 2) a one-pot
      acylation/akylation/lactonization to construct the C-ring and C8 quarternary
      center, 3) a reductive alkenylation approach to construct the enmain D/E rings
      and 4) a flexible route to allow divergent syntheses of three natural products.

PMID- 29644803
TI  - Prevalence, risk factors and adverse outcomes of anticholinergic burden in
      patients with advanced chronic conditions at hospital admission.
AB  - AIM: To evaluate the anticholinergic burden (ACB), the risk factors associated
      with its onset and the clinical consequences for patients with advanced chronic
      conditions. METHODS: A 10-month cross-sectional study was carried out in an acute
      hospital care geriatric unit. Patients with advanced chronic conditions were
      identified by the NECessity of PALliative care (NECPAL) test. The ACB was
      established using the Anticholinergic Drug Scale and Drug Burden Index (DBI)
      tools. Demographic, pharmacological and clinical patient data were collected with
      the objective of determining risk factors related to ACB. Measured clinical
      outcomes were the presence of acute confusional state, bone fractures, length of
      stay, mortality and 12-month survival rate. RESULTS: A total of 235 patients were
      recruited (mean age 86.80 years, SD 5.37 years; 65.50% women), and 82.10% (DBI)
      and 93.6% (Anticholinergic Drug Scale) of the patients were treated with
      anticholinergic medications. Excessive polypharmacy (>=10 drugs) was identified
      as a risk factor for the presence of anticholinergic medication (Anticholinergic
      Drug Scale: OR 6.26, 95% CI 1.38-28.42; DBI: OR 3.44, 95% CI 1.60-7.38). High
      anticholinergic burden (by DBI >2 points) was an independent risk factor for the
      presence of acute confusional state on hospital admission (OR 2.98, 95% CI 1.04
      8.50). However, ACB was not related to bone fractures on admission, length of
      stay, mortality or survival. CONCLUSIONS: Patients with advanced chronic
      conditions are frequently treated with anticholinergic drugs, with excessive
      polypharmacy as a risk factor. Anticholinergic drugs are a risk factor for the
      presence of acute confusional state on hospital admission, but have no other
      effect in terms of morbimortality. Geriatr Gerontol Int 2018; 18: 1159-1165.

PMID- 29644800
TI  - Defining Cell Identity with Single-Cell Omics.
AB  - Cells are a fundamental unit of life, and the ability to study the phenotypes and
      behaviors of individual cells is crucial to understanding the workings of complex
      biological systems. Cell phenotypes (epigenomic, transcriptomic, proteomic, and
      metabolomic) exhibit dramatic heterogeneity between and within the different cell
      types and states underlying cellular functional diversity. Cell genotypes can
      also display heterogeneity throughout an organism, in the form of somatic genetic
      variation-most notably in the emergence and evolution of tumors. Recent technical
      advances in single-cell isolation and the development of omics approaches
      sensitive enough to reveal these aspects of cell identity have enabled a
      revolution in the study of multicellular systems. In this review, we discuss the
      technologies available to resolve the genomes, epigenomes, transcriptomes,
      proteomes, and metabolomes of single cells from a wide variety of living systems.

PMID- 29644805
TI  - Role of autonomic nervous activity, as measured by heart rate variability, on the
      effect of mortality in disabled older adults with low blood pressure in long-term
      care.
AB  - AIM: Previous studies have shown the relationship between low blood pressure and
      high mortality in frail, disabled older adults in long-term care. However, the
      mechanism of this relationship is still unclear. We hypothesized that autonomic
      nervous activity decline is involved in the relationship between low blood
      pressure and high mortality. METHODS: The present prospective cohort study
      recruited 61 participants aged >=75 years. The data from 24-h Holter monitoring
      and blood pressure recorded by ambulatory blood pressure monitoring were
      collected. Measured data were divided into three categories: 24-h, daytime and
      night-time. From power spectral density in the electrocardiogram, low frequency,
      high frequency and low frequency/high frequency ratio were calculated. The
      primary end-point was death. RESULTS: High blood pressure was connected to both
      high daytime low frequency and high frequency (partial correlation coefficients:
      0.42, P < 0.05 and 0.35, P < 0.05, respectively). In addition, the low blood
      pressure group had higher mortality than the high blood pressure group, and
      disabled older adults in long-term care and those with elevated daytime systolic
      and diastolic blood pressure had less risk of mortality compared with those
      without (systolic: hazard ratio 0.89, 95% confidence interval 0.83-0.96, P =
      0.003; diastolic: hazard ratio 0.98, 95% confidence interval 0.79-1.00, P =
      0.049). The average blood pressures in the high blood pressure groups were
      approximately 140/80 mmHg and were connected to low mortality. CONCLUSIONS:
      Attenuated autonomic nervous activity might lead to low blood pressure in the
      daytime and high mortality in disabled older adults in long-term care. Geriatr
      Gerontol Int 2018; 18: 1153-1158.

PMID- 29644804
TI  - Relationship between the activities of daily living, oral health-related quality
      of life and dementia.
AB  - AIM: The aim of the present study was to investigate the association between the
      activities of daily living and the oral health-related quality of life and
      dementia in older adults. METHODS: Over a period of 18 months, we visited 12
      elderly care facilities and recruited 375 participants, 345 of whom were selected
      to undergo oral health examinations and oral health-related surveys. Each
      investigation was carried out face-to-face by a professional worker. RESULTS:
      Cognitive ability was found to be good when the results of the activities of
      daily living and the oral health-related quality of life examinations were good.
      If the results of the activities of daily living examination were bad, the odds
      ratio of dementia was 2.66, and adjusted odds ratio for age, sex, residence type,
      education level and denture was 2.99, representing a significant difference (P <
      0.05). CONCLUSIONS: Most oral problems are not simply the outcome of aging, with
      oral hygiene management being the most important determining factor. Oral health
      problems can be prevented, and in order to improve the quality of life of older
      adults, attention must be paid to oral healthcare. Geriatr Gerontol Int 2018; 18:
      943-949.

PMID- 29644806
TI  - "Committing Sociology" as a Value Commitment.

PMID- 29644807
TI  - Factors influencing the uptake of a mass media intervention to improve child
      feeding in Bangladesh.
AB  - Mass media are increasingly used to deliver health messages to promote social and
      behaviour change, but there has been little evidence of mass media use for
      improving a set of child feeding practices, other than campaigns to promote
      breastfeeding. This study aimed to examine the factors influencing the uptake of
      infant and young child feeding messages promoted in TV spots that were launched
      and aired nationwide in Bangladesh. We conducted a mixed-methods study, using
      household surveys (n = 2,000) and semistructured interviews (n = 251) with
      mothers of children 0-23.9 months and other household members. Factors associated
      with TV spot viewing and comprehension were analysed using multivariable logistic
      regression models, and interview transcripts were analysed by systematic coding
      and iterative summaries. Exposure ranged from 36% to 62% across 6 TV spots, with
      comprehension ranging from 33% to 96% among those who viewed the spots. Factors
      associated with comprehension of TV spot messages included younger maternal age
      and receipt of home visits by frontline health workers. Three direct narrative
      spots showed correct message recall and strong believability, identification, and
      feasibility of practicing the recommended behaviours. Two spots that used a
      metaphorical and indirect narrative style were not well understood by
      respondents. Understanding the differences in the uptake factors may help to
      explain variability of impacts and ways to improve the design and implementation
      of mass media strategies.

PMID- 29644808
TI  - Prognostic Evaluation of Neurological Assessment of the Neuro-Oncology Scale in
      Glioblastoma Patients.
AB  - BACKGROUND: The aims of this study were to investigate the role of the
      Neurological Assessment of Neuro-Oncology (NANO) scale in predicting the
      prognosis of patients with glioblastoma, and compare these results to predicted
      data of the Karnofsky Performance Scale (KPS), and Eastern Cooperative Oncology
      Group (ECOG)/World Health Organization (WHO) performance status. Additionally, we
      examined other prognostic factors in glioblastoma patients. METHODS: The medical
      records of 76 patients with a new diagnosis of histologically ascertained
      glioblastoma in the period from January 2002 to December 2015 at the authors'
      institution were retrospectively reviewed. Clinical factors, including
      epidemiologic, radiologic, and therapeutic values were reviewed as well as the
      performance status assessed by the KPS, ECOG/WHO performance status, and NANO
      scale. RESULTS: The mean overall survival was 19.8 months (95% confidence
      interval 15.2-25.4 months). At initial diagnosis, the mean value [+/-standard
      deviation (SD)] of KPS score, ECOG/WHO performance status, and NANO scale were 81
      (+/-7.4), 1.3 (+/-0.6), and 7.3 (+/-3.8), respectively. Multivariate analysis for
      predicting survival showed odds ratios of KPS score, ECOG/WHO performance status,
      and NANO scale were 2.502 (>=80 vs. <80; p=0.024), 1.691 (0-1 vs. 2-5; p=0.047),
      and 2.763 (0-7 vs. 8-23; p=0.020), respectively. At the time of progression, the
      mean value (+/-SD) of KPS score, ECOG/WHO performance status, and NANO scale were
      69 (+/-8.2), 1.6 (+/-0.7), and 11.4 (+/-4.2), respectively; multivariate analysis
      for predicting survival showed that the odd ratios for KPS score, ECOG/WHO
      performance status, and NANO scale were 2.007 (>=80 vs. <80; p=0.035), 1.321 (0-1
      vs. 2-5; p=0.143), and 3.182 (0-7 vs. 8-23; p=0.002), respectively. CONCLUSION:
      The NANO scale provided a more detailed and objective measure of neurologic
      function than that currently used for predicting the prognosis of glioblastoma
      patients, especially at the time of progression.

PMID- 29644809
TI  - Optic Nerve Sheath Meningioma: Preliminary Analysis of the Role of Radiation
      Therapy.
AB  - BACKGROUND: The purpose of this study was to evaluate the treatment outcome of
      our optic nerve sheath meningioma (ONSM) case series in terms of preventing tumor
      growth and preserving vision in ONSM patients. METHODS: Between July 2003 and
      March 2015, 1,398 patients with intracranial meningioma were diagnosed at Seoul
      National University Bundang Hospital. Among them, only 13 patients (0.93%) were
      diagnosed with ONSM and enrolled in the present study. Tumor volume changes of
      ONSM patients and their visual acuity were evaluated before and after treatments.
      RESULTS: The median follow-up time was 50 months (range, 12-133 months). Visual
      acuity was evaluated in 12 of 13 patients, and visual acuity was found to be
      preserved in 9 of 12 patients (75%). Tumor volume was reduced in all patients.
      The tumor control rate was 100% in the present study. The difference in tumor
      volume between pretreatment and last follow-up was statistically significant
      (p=0.015). CONCLUSION: Intensity-modulated radiotherapy (IMRT) and gamma knife
      radiosurgery (GKS) could maintain visual acuity and stabilize tumor volume in
      ONSM patients, suggesting that IMRT and GKS may be effective therapies for ONSM.
      However, which treatment is the more effective modality must be confirmed by
      prospective studies and longer-term follow-up.

PMID- 29644811
TI  - Nanoparticle-enabled experimentally trained wavelet-domain denoising method for
      optical coherence tomography.
AB  - We present the nanoparticle-enabled experimentally trained wavelet-domain
      denoising method for optical coherence tomography (OCT). It employs an
      experimental training algorithm based on imaging of a test-object, made of the
      colloidal suspension of the monodisperse nanoparticles and contains the
      microscale inclusions. The geometry and the scattering properties of the test
      object are known a priori allowing us to set the criteria for the training
      algorithm. Using a wide set of the wavelet kernels and the wavelet-domain
      filtration approaches, the appropriate filter is constructed based on the test
      object imaging. We apply the proposed approach and chose an efficient wavelet
      denoising procedure by considering the combinations of the decomposition basis
      from five wavelet families with eight types of the filtration threshold. We
      demonstrate applicability of the wavelet-filtering for the in vitro OCT image of
      human brain meningioma. The observed results prove high efficiency of the
      proposed OCT image denoising technique.

PMID- 29644812
TI  - Add-on Gabapentin Alleviates Paliperidone-induced Head Tremors andBoosts
      Antipsychotic Response in Early-Onset Schizophrenia

PMID- 29644810
TI  - Cystic Meningiomas: Correlation between Radiologic and Histopathologic Features.
AB  - BACKGROUND: Tumors with cysts often correlate with gliomas, metastatic tumors, or
      hemangioblastomas, which require differentiation. METHODS: Thirty-eight cases of
      cyst associated-meningioma based on preoperative radiologic studies and
      histologic confirmations were reviewed from November 1998 to July 2017. RESULTS:
      A total of 395 cases of meningioma were observed in the 20 years, and surgical
      treatment of intracranial meningioma was performed in 120 cases. Thirty-eight
      (9.6%) cases of cyst associated meningiomas were analyzed. Nauta type I was the
      most common type of cyst (39.5%) and the most frequent histopathological subtype
      was meningothelial type (36.8%). CONCLUSION: Statistically there were no
      significant associations between meningioma histopathological type and associated
      cysts; however, the rate of World Health Organization grade II was higher in cyst
      associated meningiomas than in unrelated meningiomas. This correlation was weak,
      in accordance with the meningioma grade.

PMID- 29644813
TI  - Endovascular repair of aortic arch disease with double inner branched thoracic
      stent graft: the Bolton perspective.
AB  - BACKGROUND: In the light of current evidence, endovascular repair of aortic arch
      pathologies with custom-made devices should be considered a valid alternative to
      decrease operative mortality and morbidity associated with open or hybrid repair.
      Today, two double inner branch devices are available on market. We report our
      single-center experience with Bolton double branch stent graft in the treatment
      of aortic arch disease. METHODS: Between 2013 and 2016, 15 high-risk patients
      with arch pathology were treated in our center with a custom-made branched
      device. Six of these received a Cook arch branched stent graft. Nine were treated
      with Bolton device. Among these, 2 with single branch model were excluded leaving
      a subgroup of 7 patients object of this study. RESULTS: Out of the 7 male
      patients (mean age 76, range 70-85) included in the study, 2 died in-hospital
      after stroke and retrograde dissection, respectively. No other death, major
      complication or secondary intervention was recorded at a mean follow-up of 24
      (min-max 6-53) months, neither any aneurysmal diameter evolution nor branch
      related complications. CONCLUSIONS: Despite the small sample size, our results
      are in line with the early-published experiences about this technique.
      Endovascular repair of aortic arch disease with custom-made branched devices
      should always be considered to give high-risk patients a chance of repair.

PMID- 29644814
TI  - MALARIA SELF-CARE IN NIMBORAN SUBDISTRICT, JAYAPURA DISTRICT, PAPUA PROVINCE,
      INDONESIA.
AB  - Papua is one of five provinces with high malaria incidence in Indonesia.In 2009,
      the Indonesian Ministry of Health issued decree No 293 on malariaelimination.
      Socioeconomic, culture and psychological conditions, and perceptionof malaria are
      determining factors in seeking treatment. Health seeking behavioralso are
      influenced by enabling factors, such as income and health insurance;and by health
      providers, such as availability of health care facilities, tariffs andliving
      locationss. Self-care is one form of community participation in
      knowledge,prevention and early detection of malaria, and in seeking treatment and
      complianceto malaria treatment, especially among inhabitants in malaria
      endemicareas. This study was an observation in Nimboran Subdistrict, Jayapura
      District,Papua Province, Indonesia during 2013. Thirty individuals from 'Pengurus
      RukunTetangga' group were chosen randomly for the survey. Facts evaluated
      wereknowledge of cause of malaria, disease transmission, symptoms and
      complication,diagnosis, treatment and side effects, medical seeking behavior and
      treatment,vector breeding sites, and attitude towards compliance of malaria
      treatment anduse of mosquito nets. Self-care against malaria was considered
      important by 65%of the respondents. All participants had visited health centers
      and complied withprescribed drug regimen. All respondents with malaria-infected
      neighbors visitedhealth centers. Regarding antimalarial malaria drugs, the
      majority of respondentsknew of Darplex(r) and were aware that a common side
      effect of antimalarials wastinnitus. The majority of respondents identified ponds
      as malaria vector breedingplaces and recognized the importance of managing
      vectors in malaria prevention.The study concludes that malaria self-care was
      needed for awareness, preventionand treatment of this debilitating disease.

PMID- 29644815
TI  - A SIMPLE AND EFFECTIVE MULTIPLEX PCR TECHNIQUE FOR DETECTING HUMAN PATHOGENIC
      TAENIA EGGS IN HOUSEFLIES.
AB  - Taenia solium, T. saginata, and T. asiatica are cestode pathogens
      causingtaeniasis in humans. Houseflies can transfer Taenia eggs to food.
      However,houseflies are thought to carry only small numbers of Taenia eggs,
      sometimesfewer than 10. Although several PCR-based methods have been developed
      todetect Taenia DNA, these require more than 10 eggs for adequate detection.
      Wedeveloped a multiplex PCR method with high specificity for the
      discriminationamong the eggs of the three Taenia species, T. solium, T. saginata,
      and T. asiatica,using 18S ribosomal DNA (rDNA) as a genetic marker. This
      technique was foundto be highly sensitive, capable of identifying the Taenia
      species from only one egg.This multiplex PCR technique using 18S rDNA specific
      primers should be suitableto diagnose Taenia eggs.

PMID- 29644816
TI  - PRELIMINARY SURVEY OF ENTOMOPATHOGENIC NEMATODES IN UPPER NORTHERN THAILAND.
AB  - Entomopathogenic nematodes (EPNs) of the genera Steinernema andHeterorhabditis
      are used as biocontrol agents for insect pests. Survey of indigenousEPNs provides
      not only the diversity aspects but also the contribution in pestmanagement in
      local areas. The objective of this study was to survey EPNs inupper northern
      Thailand. Nine hundred seventy soil samples were obtained from194 sites in upper
      northern region of Thailand; of these 60 (6.2%) had EPNs in 2genera: Steinernema
      (32 isolates) and Heterorhabditis (28 isolates). Most EPNs wereisolated from loam
      with a soil temperature of 24-38 degrees C, a pH of 1.5-7.0 and a soilmoisture
      content of 0.5-6.8%. Molecular identification based on sequencing of apartial
      region of an internal transcribed spacer was performed for Heterorhabditisand the
      28S rDNA for Steinernema. A BLASTN search of known sequence EPNsrevealed 24
      isolates of S. websteri and one isolate of S. scarabaei were identified;closely
      related to S. websteri (accession no. JF503100) and S. scarabaei (accessionno.
      AY172023). The Heterorhabditis species identified were: H. indica (11
      isolates),H. gerrardi (2 isolates) and Heterorhabditis sp (8 isolates).
      Phylogenetic analysisrevealed 11 isolates of Heterorhabditis were related to H.
      indica; 2 isolates were relatedto Heterorhabditis gerrardi and 8 isolates were
      closely related to Heterorhabditissp SGmg3. The study results show the genetic
      diversity of EPNs and describe anew observation of S. scarabaei and H. gerrardi
      in Thailand. This finding is newand provides important information for further
      study on using native EPNs inbiological control.

PMID- 29644817
TI  - LARVICIDAL AND PUPICIDAL ACTIVITIES OF CRUDE AND FRACTIONATED EXTRACTS OF ACACIA
      PENNATA (L.) WILLD. SUBSP INSUAVIS SHOOT TIPS AGAINST AEDES AEGYPTI (L.)
      (DIPTERA: CULICIDAE).
AB  - Acacia pennata subsp insuavis, or Cha-om in Thai, is a common vegetablefound in
      Thailand. It has been used as a medicinal herb for a long time. From
      theliterature, antinociceptive, anti-inflammatory, antimicrobial, and anti
      helminthicactivities were reported. In this study, we investigated two new
      actions of thisplant: larvicide and pupicide. The crude ethanolic and
      fractionated extracts of A.pennata shoot tips were tested against aquatic stages
      of the dengue virus vector,Aedes aegypti mosquito. The 1st-4th instar larvae and
      pupae of Ae. aegypti weresubjected for bioassays by following the standard
      protocol of WHO. The larvaland pupal mortalities were observed after 24- and 48
      hour exposure times. Thebioassays demonstrated that stronger efficacy was found
      from the fractionatedextracts than the crude extracts. The LC50 values against
      the 3rd instar larvae were39.45-50.75 mg/l (fractionated extracts) and 244.50
      mg/l (crude extracts). It alsoeffects the pupae with the LC50 values of 44.10
      53.73 mg/l and 87.27 mg/l for thefractionnated and the crude extracts,
      respectively. The bioassays demonstratedthe effective mosquito larvicide and
      pupicide of A. pennata extracts. It could bean alternative candidate for the
      development of phytotoxin for controlling mosquitovectors.

PMID- 29644818
TI  - SURVEILLANCE IN 2013 OF AVIAN INFLUENZA VIRUS FROM LIVE-BIRD MARKETS IN BANGKOK,
      THAILAND.
AB  - Live-bird markets have been implicated in transmission of avian influenzaviruses,
      most recently of influenza A (H7N9) in China. Low pathogenic avianinfluenza
      (LPAI) viruses, such as H7N9, cause asymptomatic infections in poultry,and active
      surveillance is required to detect infection and to prevent transmissionto
      humans. Although limited numbers of live birds for consumption are sold inBangkok
      live bird markets (LBM), transmission of H7N9 in nearby China hasprompted a
      program of active surveillance for avian influenza in Bangkok LBM todetermine
      LPAI viruses. In November 2013, Bangkok One Health team organizedavian influenza
      surveillance in all nine districts of Bangkok with LBMs. Oropharyngealswabs (n =
      834), sera (n = 375) and fresh feces (n = 420) were taken from400 chickens, 20
      ducks, 20 geese and 394 pet birds from 75/87 shops. Additionally,drinking water
      (n = 208) and waste water (n = 26) were collected. Samples weretested for
      influenza A viruses using RT-PCR. In addition, samples were inoculatedin eggs and
      tested by hemagglutination (HA) and hemagglutination inhibition(HI) assays using
      H5N1- and H7N9-specific antigens. Sera were tested by HI assayusing similar
      antigens. No sample was found positive for influenza A virus.These data provide
      evidence that avian influenza viruses, including LPAI virusessuch as H7N9, were
      not circulating in Bangkok LBMs during the period surveyed.

PMID- 29644819
TI  - CONSTRUCTION AND EXPRESSION OF H5N1 INFLUENZA VIRUS HEMAGGLUTININ-SPECIFIC scFv
      Fc MONOCLONAL ANTIBODIES IN HEK293T CELLS.
AB  - Monoclonal antibody (MAb) is a key element in the development ofrapid test kits
      for many infectious diseases. Our group previously developedtwo antigen-binding
      fragment (Fab) MAbs, H5Fab-6 and H5Fab-9, specific tohemagglutinin (H5 HA) of
      influenza A virus H5N1, but these Fabs do not have aconstant fragment (Fc)
      portion with which to bind with gold particles in a striptest. In order to
      overcome this impediment, we joined a single-chain variable fragment(scFv) with
      an Fc region to produce a scFv-Fc MAb, which was expressed inmammalian HEK293T
      cells. Specificity and sensitivity of each generated scFv-FcMAb for H5 HA was
      tested using western blotting and dot-enzyme-linked immunosorbentassay (dot
      ELISA), respectively. Two scFv-Fcs (designated H5scFvFc-6and H5scFvFc-9) were
      constructed and purified to near homogeneity with a yieldof 12.87 mg/l and 33.56
      mg/l, respectively. Western blotting indicated that bothscFv-Fcs reacted as
      expected with H5 HA with a sensitivity of 60 pg of H5 HA.These scFv-Fc MAbs
      should prove useful in the development of antibody-baseddiagnostic tools.

PMID- 29644820
TI  - CLINICAL OUTCOMES OF CRYPTOCOCCAL MENINGITIS AMONG HIV-INFECTED PATIENTS IN THE
      ERA OF ANTIRETROVIRAL THERAPY.
AB  - Cryptococcal meningitis (CM) is a common opportunistic infection inHIV-infected
      patients and the clinical outcome can be severe. This study aimed todetermine the
      survival rate and prognostic factors among HIV-infected patientswith CM in the
      era of antiretroviral therapy (ART). Understanding of these factsmay help
      clinicians to manage CM patients efficiently and patients with poorprognostic
      factors could be closely monitored. We conducted a retrospective cohortstudy
      among new cases of HIV-associated CM who were treated at RamathibodiHospital,
      Mahidol University, Thailand, during 2002-2013. Of 195 patients, 119(61%) were
      male; the median (interquartile range, IQR) age was 33 (29-39) years.The median
      (IQR) CD4 cell count was 20 (9-44) cells/mm3. The median survivaltime was >12
      years and the 75% survival time was 5 years. Using the Cox proportionalhazard
      model, the factors associated with mortality were impaired consciousness[hazard
      ratio (HR)=2.38; 95% confidence interval (CI): 1.03-5.50], lowinitial
      cerebrospinal fluid (CSF) protein (<=60 mg/dl) (HR=2.88; 95%CI: 1.13-7.35),low
      initial CSF glucose (<=30 mg/dl) (HR=2.36; 95%CI: 1.01-5.51), high
      openingpressure during induction therapy (>25 cmH2O) (HR=2.90, 95%CI: 1.21-6.94),
      noART (HR=14.8; 95%CI: 5.39-40.7) and relapse of CM (HR=4.31; 95%CI: 1.42
      13.1).The HIV-associated CM survival rate in the ART era is higher than it was
      duringthe pre-ART era.

PMID- 29644822
TI  - BURKHOLDERIA PSEUDOMALLEI BIOFILM PLAYS A KEY ROLE IN CHRONIC INFLAMMATION IN
      C57BL/6 MICE.
AB  - Burkholderia pseudomallei is a causative agent of melioidosis. Clinicalsigns of
      melioidosis vary from acute septicemia to chronic inflammation or
      subclinicalinfection. This study investigated the role of B. pseudomallei biofilm
      inchronic inflammation in lungs of infected C57BL/6 mice. Low doses of B.
      pseudomalleiH777 and its biofilm defective M10 mutant were fed intra-gastrically
      toC57BL/6 mice and inflammatory responses were investigated by
      histopathologicaltechniques. Two hundred colony forming units (CFUs) of B.
      pseudomallei H777induced chronic inflammatory responses in mice on day 20 post
      infection, withdiscrete interstitial infiltration by mononuclear inflammatory
      cells. On day 40 postinfection,there were marked thickening of alveolar septa and
      congested capillaries,which increased in severity by day 60. On the other hand,
      mice infected with B.pseudomallei M10 showed less mononuclear infiltration. The
      results indicate thatB. pseudomallei defective in biofilm production gave rise to
      less severe pathology,resulting a higher rate of survival in infected mice; and
      pulmonary melioidosiscould be developed in C57BL/6 mice by intra-gastric feeding
      makes it a possibleanimal model of chronic human melioidosis.

PMID- 29644821
TI  - SEROPREVALENCE OF RUBELLA ANTIBODIES AMONG TURKISH AND FOREIGN WOMEN IN TURKEY.
AB  - The aims of this study were to determine seroprevalence of rubella
      antibodiesamong Turkish and foreign women living in Turkey and to estimate
      percentwomen susceptible to rubella infection. This retrospective study was
      conductedamong 970 women (816 Turks) attending gynecology and obstetrics
      outpatientclinics. Serum samples were tested for anti-rubella IgG and IgM by
      chemiluminescentmicroparticle immunoassay. Eighty-eight percent of the subjects
      were positiveonly for anti-rubella IgG indicating immunity to rubella infection,
      none for onlyanti-rubella IgM and 1.5% for both anti-rubella IgM and IgG, the
      latter having ahigh avidity of anti-rubella IgG signifying a previous infection.
      Anti-rubella IgGseropositivity rate alone for Turkish women is 86.1%,
      significantly higher thanthat for foreign women. A significant association
      between age and seropositivitywas found only for the age group of 15-20 years
      among both Turkish and foreignwomen. Anti-rubella IgG seropositivity rate of
      pregnant women increased withincreasing age from 10.7% (at 15-20 years old) to
      85.5% (at 36-40 years old). Amongnon-pregnant women, both anti-rubella IgM and
      IgG seronegativity rates weresignificantly higher in the age group of 31-35 years
      than the other age groups. Ourresults indicate that all pregnant women in Turkey
      should routinely be screenedfor anti-rubella IgM and IgG at antenatal period.
      Evaluation of susceptibility ofwomen in reproductive age to rubella infection is
      important to setup a strategyfor preventing antenatal rubella through vaccination
      of non-immune womenthroughout the country.

PMID- 29644823
TI  - DISTRIBUTION OF VIRULENCE GENES IN ENVIRONMENTAL AND CLINICAL ISOLATES OF
      LEGIONELLA PNEUMOPHILA IN BUSAN, SOUTH KOREA.
AB  - Legionella pneumophila is the major causative agent of Legionnaires' disease.The
      distribution of L. pneumophila in environmental water systems of publicfacilities
      in Busan, South Korea was previously reported; however, the distributionof
      virulence genes in environmental and clinical isolates in Busan is unknown.Here,
      we investigated using PCR the distribution of three virulence loci (dot/icm,lvh,
      and rtxA) in isolates from Busan. A high prevalence of environmental (127/254)and
      clinical (3/4) isolates were observed for the simultaneous presence of all
      threegenes, while environmental harboring dot/icm + rtxA, dot/icm + lvh, rtxA +
      lvh, andonly one gene were 21%, 11%, 9% and <1-4%, respectively, The remaining
      clinicalisolate carried dot/icm + rtxA. In addition, 68% of isolates from
      serogroup 1, themain cause of legionellosis, possessed all three virulence genes
      compared with40% of isolates from serogroups 2 to 15. Prevalence of isolates with
      two genes was5-14% and 6-29% in serogroup 1 and serogroups 2 to 15, respectively,
      whereasthat of isolates with one gene was 1-2% and 0-6%, respectively. These
      results providevaluable information for epidemiological investigations of the
      relationshipbetween environmental and clinical isolates in legionellosis
      outbreaks in Busan.

PMID- 29644824
TI  - [Post-exposure prophylaxis against HIV, the view from the emergency department -
      authos's response].

PMID- 29644825
TI  - INVASIVE SALMONELLOSIS PRESENTING AS A LUNG ABSCESS: A CASE REPORT.
AB  - Salmonella spp are an uncommon cause of lung abscess. A 59 year oldman presented
      to our hospital with a 1 month history of cough and low gradefever progressing to
      high grade fever for 1 week. He had a past medical historysignificant for
      diabetes mellitus type 2 and focal segmental glomerulosclerosisfor which he was
      receiving prednisolone, initially at 60 mg daily tapering to 20mg daily. On
      presentation he was febrile and had decreased breath sounds anddullness to
      percussion over the right lower lung field. A chest X-ray showed acavitary lesion
      with an air-fluid level in the right lung. Computed tomographyof the lung
      revealed 2 cavitary lesions in the right upper and lower lungs. Sputumculture
      revealed Salmonella spp group B. He was treated successfully withceftriaxone
      intravenously for 1 month followed by oral cefdinir. A chest X-ray at1 month
      showed significant improvement; he was treated conservatively withoutsurgical
      drainage. Salmonella can cause lung abscesses, especially in the
      immunesuppressed.

PMID- 29644826
TI  - CHARACTERIZATION OF EXTRAINTESTINAL PATHOGENIC ESCHERICHIA COLI FROM MEAT IN
      SOUTHERN THAILAND.
AB  - Extraintestinal pathogenic Escherichia coli (ExPEC) is an E. coli group,which
      causes diseases in systems outside human intestinal tract. ExPEC isolateswere
      recovered from fresh chicken (25%) and pork (10%) meats, but not beef andshrimp,
      from markets in southern Thailand. Among the 14 ExPEC strains isolated,all
      carried iutA and fimH, coding for aerobactin and type 1 fimbriae,
      respectively.Two ExPEC strains from chicken meat possessed kpsMTK1 coding for K1
      capsularantigen, responsible for neonatal meningitis. Antimicrobial
      susceptibility assayrevealed that all ExPEC were resistant to streptomycin and
      carried blaTEM, butsusceptible to imipenem. Phylogenetic group analysis showed
      that 4, 4, and 6ExPEC strains belonged to group A, B1 and D, respectively. ExPEC
      strains wereclassified into four serotypes, namely, O8 (2 strains), O15 (2
      strains), O25 (1 strain),and O127a (1 strain), with the remaining untypeable. DNA
      profiling analysis byBOX-PCR revealed clonality of strains with the same
      serotype. The existence ofExPEC in meat products should cause concern regarding
      food safety and publichealth not only in southern Thailand but also throughout
      the country.

PMID- 29644827
TI  - ANTIBACTERIAL PROPERTIES OF SELECTED PLANTS CONSUMED BY PRIMATES AGAINST
      ESCHERICHIA COLI AND BACILLUS SUBTILIS.
AB  - Bacterial antimicrobial resistance is a major health problem worldwide.Plants
      consumed by non-human primates are potentially safe for humans. In thisstudy, we
      examined the potential antibacterial properties of plants consumed bynon-human
      primates in Indonesia. We studied the antibacterial properties of theleaf
      extracts of 34 primate-consumed plants against Escherichia coli and
      Bacillussubtilis in vitro. The plants were collected from the Pangandaran
      ConservationArea, West Java Province, Indonesia. The leaves were dried and then
      powderedby crushing and the potential active ingredients were extracted with 95%
      ethanolat room temperature for 24 hours. The obtained solvent was then dried at
      50oCunder reduced pressure. The antibacterial properties of each product were
      thentested to determine the minimum inhibitory and minimum bactericidal
      concentrationsusing the broth microdilution technique and a disc diffusion test
      was alsoperformed. The results show Kleinhovia hospita, Dillenia excelsa and
      Garcinia celebicahad the best antibacterial properties against Escherichia coli
      and Ficus benjamina,Ficus altissima, and Elaeocarpus glaber had the best
      antibacterial properties againstBacillus subtilis. Some of the studied leaf
      extracts in our study have the potentialto be developed into antibacterial
      medications and need to be studied further.

PMID- 29644828
TI  - ANTIBACTERIAL PROPERTY TESTING OF TWO SPECIES OF TROPICAL PLANT LASIANTHUS
      (RUBIACEAE).
AB  - Two tropical plant species, Lasianthus pilosus and Lasianthus stipularisare used
      in traditional medicine but there have been no published studies of theextracts
      of these plants against bacteria. In this study, we aimed to determinethe
      antimicrobial activities of the above two plants against two gram-positiveand
      seven gram-negative bacterial strains to determine the potential of thesetwo
      plant species for possible antimicrobial drug development. The
      antibacterialactivities of the lipophilic extracts of these plants were evaluated
      by diskdiffusion and broth microdilution methods. The zone diameters and
      minimuminhibitory concentrations (MIC) for these plant extracts exhibited their
      highestantibacterial activity against Pseudomonas aeruginosa, followed by
      Staphylococcusaureus and Acinetobacter baumannii, respectively. The MIC of these
      extracts againstP. aeruginosa (ATCC 37166 and ATCC 27853) varied from 50 to 200
      MUg/ml. Thinlayer chromatography and detection using different specific reagents
      revealedthe presence of terpenoids, phenolic compounds and iridoid. Cell lysis
      due tothe effect of the lipophilic extracts of these tested plants was
      demonstrated usingscanning electron microscopy. In conclusion, the bioactive
      compounds of theseplants should be studied further to develop potential
      antimicrobial agents.

PMID- 29644829
TI  - MULTIPLE-LOCUS VARIABLE-NUMBER TANDEM REPEAT ANALYSIS OF BRUCELLA ISOLATES FROM
      THAILAND.
AB  - Brucellosis-induced abortion can result in significant economic lossto farm
      animals. Brucellosis can be transmitted to humans during slaughter ofinfected
      animals or via consumption of contaminated food products. Strain identificationof
      Brucella isolates can reveal the route of transmission. Brucella strainswere
      isolated from vaginal swabs of farm animal, cow milk and from humanblood
      cultures. Multiplex PCR was used to identify Brucella species, and owingto high
      DNA homology among Brucella isolates, multiple-locus variable-numbertandem repeat
      analysis (MLVA) based on the number of tandem repeats at 16 differentgenomic loci
      was used for strain identification. Multiplex PCR categorizedthe isolates into B.
      abortus (n = 7), B. melitensis (n = 37), B. suis (n = 3), and 5 ofunknown
      Brucella spp. MLVA-16 clustering analysis differentiated the strains intovarious
      genotypes, with Brucella isolates from the same geographic region beingclosely
      related, and revealed that the Thai isolates were phylogenetically distinctfrom
      those in other countries, including within the Southeast Asian region. Thus,MLVA
      16 typing has utility in epidemiological studies.

PMID- 29644830
TI  - ACUTE CHOLECYSTITIS AS AN UNUSUAL PRESENTATION OF SCRUB TYPHUS: A REPORT OF TWO
      CASES AND REVIEW OF THE LITERATURE.
AB  - Scrub typhus rarely presents with acute cholecystitis. We present 2 casesof scrub
      typhus with cholecystitis. The first patient is a 62 year old female whopresented
      to the hospital with fever and body aches for 1 week and right upperquadrant
      abdominal pain for 3 days. She gave a history of an insect bite 2
      weekspreviously. She was diagnosed as having acute cholecystitis and underwent
      cholecystectomy.She continued with fever post-operatively and physical
      examinationrevealed an eschar. She had an immunofluorescence assay (IFA)
      performed thatrevealed a high IgM titer for Orientia tsutsugamushi. She was
      diagnosed as havingscrub typhus, treated with doxycycline and she recovered
      completely. The secondpatient also presented to the hospital with a 1 week
      history of fever and upperquadrant abdominal pain. She was diagnosed with having
      cholecystitis. Hersymptoms did not improve with intravenous antibiotics and
      further investigationrevealed elevated titers for O. tsutsugamushi and Leptospira
      interrogans. She wasdiagnosed as having a co-infection of scrub typhus and
      leptospirosis and treatedwith doxycycline. She recovered completely. Patients
      from scrub typhus endemicregions who present with acute cholecystitis but do not
      respond to traditionaltreatment should be tested for scrub typhus and
      leptospirosis and should have acareful admission physical examination looking for
      eschar formation, since scrubtyphus may present with acute cholecystitis.

PMID- 29644831
TI  - ANTIFUNGAL ACTIVITY OF CINNAMALDEHYDE AGAINST CANDIDA ALBICANS.
AB  - Candida albicans is a common pathogen, especially among
      immunocompromisedpatients. It is beginning to show resistance against the azole
      druggroup, which is usually used to treat this pathogen. We studied the
      antifungaleffects of cinnamaldehyde against C. albicans. Germ tube formation of
      C. albicansexposed to cinnamaldehyde was determined by the crystal violet based
      method.The effect of cinnamaldehyde on adhesion of C. albicans to buccal
      epithelial cellswas investigated. Proteinase and phospholipase activities of C.
      albicans in thepresence of cinnamaldehyde were assessed using bovine serum
      albumin agar andegg yolk agar, respectively. In this study, cinnamaldehyde
      possessed antifungalactivity against C. albicans with a minimum inhibitory
      concentration of 125 MUg/ml.At sub-inhibitory concentrations, cinnamaldehyde
      significantly reduced germ tubeformation, proteinase and phospholipase activities
      in a dose dependent manner(p<0.01). Cinnamaldehyde also significantly inhibited
      the adhesion of C. albicans tobuccal epithelial cells (p<0.01). In our study,
      cinnamaldehyde had in vitro activityagainst C. albicans and inhibited some of its
      virulence factors.

PMID- 29644832
TI  - INVASIVE FUNGAL INFECTION AMONG FEBRILE PATIENTS WITH CHEMOTHERAPY-INDUCED
      NEUTROPENIA IN THAILAND.
AB  - Invasive fungal infections (IFI) can cause serious morbidity and mortalityamong
      febrile patients with chemotherapy-induced neutropenia (CIN). Inorder to evaluate
      the incidence, treatment outcome and factors associated with IFIin this patient
      population in Thailand, we retrospectively reviewed the medicalrecord of patients
      admitted to Siriraj Hospital from January 2008 to June 2010.Criteria used to
      diagnosed IFI were those of the European Organization for Researchand Treatment
      of Cancer/Invasive Fungal Infections Cooperative Groupand the National Institute
      of Allergy and Infectious Diseases/Mycoses StudyGroup (EORTC/MSG) consensus 2008
      criteria. Three hundred ten episodes ofchemotherapy-induced neutropenia occurred
      in 233 patients. IFI were found in37 episodes (12%) and occurred only in patients
      who received chemotherapy forhematological malignancies. The incidence of IFI
      among patients with hematologicmalignancies was 14%. Most commonly occurred in
      AML patients (17%). Patientswho received aggressive induction chemotherapy
      regimens for AML had thehighest incidence of IFI (20.5%). Of the 37 episodes, 12
      were candidiasis, 5 wereaspergillosis, 1 was zygomycosis, 1 was fusariosis, 10
      were probable and 9 werepossible IFI. The IFI-related mortality was 35%. The
      clinical factor associated withIFI was a temperature > 39  degrees C during
      febrile neutropenia. A higher mortality ratewas seen in patients aged > 40 years
      and those with a serum albumin level < 3 g/dl.

PMID- 29644833
TI  - GROWTH-INHIBITORY EFFECTS OF FARNESOL AGAINST SCEDOSPORIUM BOYDII AND
      LOMENTOSPORA PROLIFICANS.
AB  - Scedosporium boydii and Lomentospora prolificans are filamentous fungireported to
      cause infection in immunocompromized individuals. We studiedthe effect of
      farnesol to inhibit growth of S. boydii and L. prolificans by measuringcolony
      diameter and determining minimal effective concentration (MEC). S.boydii and L.
      prolificans were grown on Sabouraud dextrose agar (SDA) at 37oCfor 5 days.
      Conidia were collected and adjusted to a concentration of 104 conidia/ml. Twenty
      microliters of conidia suspension was placed in each well of a sixwellplate
      containing serial dilutions of farnesol (10 MUM, 100 MUM, 1,000 MUM, and10,000
      MUM) in SDA. Colony morphology and diameter were observed on days 1,2, 3, and 4.
      Farnesol at concentrations of 1,000 MUM or higher caused the colonydiameter of
      both S. boydii and L. prolificans to be smaller than untreated controlsin a dose
      dependent manner. The MEC of farnesol to inhibit growth of both S.boydii and L.
      prolificans was 3.2 mM. This study reveals the antifungal propertyof farnesol
      against S. boydii and L. prolificans, which can be used for further studyas an
      alternative antifungal agent against these fungal infections.

PMID- 29644834
TI  - 31P-MR spectroscopy in patients with mild and serious lower limb ischemia.
AB  - BACKGROUND: 31P-MR spectroscopy is a technique for undertaking a comprehensive
      evaluation of muscle metabolism. The goal of this study was to compare patients
      with mild and severe lower limb ischemia measured by 31P-MR spectroscopy at rest
      and during exercise. METHODS: Sixteen non-diabetic mild peripheral arterial
      occlusive disease (PAOD) patients, 23 diabetic PAOD patients with severe ischemia
      and 19 healthy controls were examined by rest and dynamic 31P-MR spectroscopy
      with a 3T MR system equipped with an MR-compatible home-made pedal ergometer.
      Signal intensity ratios of phosphorous metabolites to the sum of all 31P
      intensities (Ptot) and pH were obtained at rest. The PCr drop (DeltaPCr), time
      recovery constant of PCr (tauPCr), pH at the end of the exercise (pHend), and
      mitochondrial capacity (Qmax) were calculated from dynamic MR spectra. RESULTS:
      Diabetic PAOD patients with severe ischemia differed from controls in both rest
      (PCr/Pi, betaATP/Ptot, pH) and dynamic (Qmax, pHend, tauPCr) parameters. PAOD
      patients with mild ischemia differed from controls only in Qmax and pHend. Rest
      parameters of the nondiabetic PAOD patients did not differ from control values
      excluding rest pH which was higher in both patient groups. CONCLUSIONS: A
      combination of rest and dynamic 31P-MR spectroscopy can distinguish among all
      three groups of subjects. On the other hand, examination at rest is sufficient
      for differentiation between patient groups and verification of severe ischemia.

PMID- 29644835
TI  - Risk assessment as a guide for the prevention of cancer-associated
      thromboembolism.
AB  - Venous thromboembolism (VTE) is a major source of morbidity and mortality among
      patients diagnosed with cancer. In addition to an increased risk of VTE, patients
      with cancer are at higher risk of bleeding while receiving therapeutic
      anticoagulation. Aggressive and targeted thromboprophylaxis is a crucial practice
      to avoid the dreaded complications of VTE. Risk assessment models (RAM) are tools
      developed to identify high-risk patients in whom thromboprophylaxis is
      beneficial. This review describes the most validated VTE RAMs in patients with
      cancer.

PMID- 29644836
TI  - Elevated extracellular nucleosomes and their relevance to inflammation in stage 5
      chronic kidney disease.
AB  - BACKGROUND: Chronic kidney disease is a disorder characterized by a pro
      inflammatory state that is associated with increased morbidity and mortality.
      Endogenous damage-associated molecular patterns, including nucleosomes, may
      contribute to this persistent inflammation. The aim of this study was to profile
      and evaluate the clinical significance of circulating nucleosomes in patients
      with Stage 5 chronic kidney disease (CKD5) on hemodialysis (HD). METHODS: Under
      institutional review board approval, plasma samples were collected from 90 CKD5
      HD patients (45 male and 45 female) prior to hemodialysis. Normal human plasma
      samples (25 male and 25 female) were used as a control group. Commercial enzyme
      linked immunosorbent and colorimetric assays were used to profile nucleosome
      levels and biochemical markers of kidney injury, inflammation, thrombosis, and
      renal function in CKD5-HD and control groups. Clinical laboratory parameters were
      documented from the electronical medical record and correlated to nucleosome
      levels in the CKD5-HD cohort. RESULTS: In comparison to healthy volunteers, the
      plasma from CKD5-HD patients exhibited markedly elevated nucleosomes (P<0.0001).
      Furthermore, nucleosome levels correlated with WBC count (P=0.025, R=0.243) and
      CRP (P=0.019, R=0.266) levels. No correlation was found between nucleosomes and
      the other parameters studied. CONCLUSIONS: Our findings indicate extracellular
      nucleosomes are significantly elevated in CKD5-HD, suggesting increased cell
      death and/or inflammation. The observed correlations between nucleosomes and
      parameters of inflammation is suggestive of a complex, systemic inflammatory
      process underlying renal deterioration, consistent with the literature. Thus,
      nucleosomes may play a role in the pathogenesis and outcome of CKD5-HD.

PMID- 29644837
TI  - RAPIDLY PROGRESSIVE PULMONARY CRYPTOCOCCOSIS WITH CAVITATION IN AN
      IMMUNOCOMPETENT WOMAN: A CASE REPORT AND LITERATURE REVIEW.
AB  - Pulmonary cryptococcosis with pulmonary cavitation is rare, especiallyin
      immunocompetent cryptococcosis patients. We describe here a case of
      rapidlyprogressive pulmonary with cavitation in an immunocompetent woman. A29
      year-old woman had a routine chest X-ray as part of a routine examination.
      Thechest X-ray showed pulmonary nodules. She was diagnosed as having
      bacterialpneumonia even though she had no symptoms and was treated with
      ampicillinorally. A chest X-ray was repeated 12 days later as follow-up which
      showed anincrease in the nodules. She continued to be asymptomatic and had a
      normallung examination. Her complete blood count revealed a normal white blood
      cellcount and her anti-human immunodeficiency virus test was normal, as were
      herimmunoglobulin levels and CD4 counts. She had a computed tomography (CT)scan
      of the lungs that showed two pulmonary nodules, one with cavitation. Shethen
      underwent a CT guided needle biopsy of the cavitary lesion which
      revealedpulmonary cryptococcosis. A serum latex cryptococcal antigen test
      revealed atiter of 1:32. She was treated with fluconazole 400 mg IV daily for 7
      days, followedby oral fluconazole 200 mg daily for a year. The cavitary lesion
      graduallydisappeared and the nodules decreased in size. A follow-up CT 1 year
      later wasnormal. Although rare, cryptococcosis of the lungs with pulmonary
      cavitation canoccur in otherwise healthy patients, requiring long term treatment
      to improve.

PMID- 29644838
TI  - DERMAL MYIASIS CAUSED BY THE FLESH FLY, PARASARCOPHAGA (LIOSARCOPHAGA) DUX
      (THOMSON, 1869) (DIPTERA: SARCOPHAGIDAE) AT THE SITE OF A MALIGNANT MELANOMA: A
      CASE REPORT.
AB  - Dermal myiasis due to the flesh fly has not been commonly reportedin Thailand. A
      64-year-old man came to the hospital with a 6-month history of ablack tumor on
      the dorsum of the right great toe. The tumor was biopsied anddetermined to be a
      malignant melanoma. Second instar larvae were also seen inthe wound and one larva
      was reared until the adult stage wherein it was identifiedas the flesh fly,
      Parasarcophaga (Liosarcophaga) dux (Thomson, 1869) (Diptera:Sarcophagidae). This
      case shows myiasis due to synanthropic sarcophagid fliesoccurs in Thailand and
      can occur in a malignant melanoma.

PMID- 29644839
TI  - FATAL HONEY POISONING IN SOUTHWEST CHINA: A CASE SERIES OF 31 CASES.
AB  - Honey poisoning cases occur in southwestern China. In this case series,we
      attempted to determine the symptoms and causes of honey poisoning from2007 to
      2012 in southwestern China. We also conducted a quantitative
      melissopalynologicalanalysis of honey samples. During the study period, 31
      honeypoisoning cases occurred in the study location, all during July to August.
      All thecases occurred after consuming at least 100 grams of honey. The most
      frequentsymptoms were nausea and vomiting (100%), abdominal pain (90.3%),
      diarrhea(74.2%), palpitations (61.3%), dizziness (54.8%), chest congestion
      (48.4%) anddyspnea (48.4%). Severe cases developed oliguria/anuria, twitch,
      hematuria, ecchymosisor hematochezia. The median time from ingestion to onset of
      symptomswas 29 hours. Eight patients died (mortality rate: 25.8%). The pollen of
      Tripterygiumhypoglaucum (a plant with poisonous nectar and pollen) was detected
      in 22 of 29honey samples examined (75.9%). The results of pollen analysis were
      consistentwith the clinical findings of previous cases. T. hypoglaucum appears to
      be the causeof honey poisoning in southwestern China. Honey poisoning should be
      includedin the differential diagnosis of patients who consume honey in this
      region anddevelop symptoms of food poisoning.

PMID- 29644840
TI  - AN OUTBREAK OF TETRODOTOXIN POISONING FROM CONSUMING HORSESHOE CRABS IN SABAH.
AB  - The horseshoe crab (Carcinoscorpius rotundicauda) is consumed by thoseresiding
      near the coastal areas of Kota Marudu District in Malaysia, as it is considereda
      delicacy. During June to August, 2011 thirty cases of tetrodotoxin poisoningwere
      reported from Kota Marudu District following ingestion of horseshoecrabs caught
      in Kota Marudu Bay. The purpose of this study is to describe thiscase series in
      order to determine risk factors to prevent further outbreaks. Therewere six
      confirmed and 24 probable cases of tetrodotoxin poisoning identified inthe study
      area during the study period as diagnosed by clinical presentation andlaboratory
      findings. Symptoms included dizziness (80%), circumoral and lingualnumbness
      (80%), hand and feet numbness (63.3%), nausea and vomiting (30%)and weakness and
      difficulty in breathing (26.6%). Three cases (10%) died while 27cases recovered.
      Forty-seven percent of the cases had onset of symptoms within30 minutes of
      ingestion and 14% 31-60 minutes after ingestion of horseshoe crabmeat. Urine
      samples were collected from the cases, while horseshoe crabs, cocklesand sea
      water from the epidemic area were also taken for analysis. Tetrodotoxinwas
      detected in the urine of six cases; the highest concentrations recorded wereamong
      the three cases who died. High tetrodotoxin concentrations were foundin the
      hepatic cecum and eggs of the tested horseshoe crabs. Dinoflagellates werenot
      detected in the sea water or cockle samples. Intensive health education
      wasinitiated quickly to stop other members of the Marudu Bay community
      fromconsuming the horseshoe crabs. This is the first documented epidemic of
      tetrodotoxinpoisoning in Sabah.

PMID- 29644841
TI  - HEALTHCARE-ASSOCIATED INFECTIONS AT SELECTED HOSPITALS IN THAILAND.
AB  - This study aimed to determine the prevalence of healthcare-associatedinfections
      (HAIs), all-cause mortality, document the bacterial pathogens isolated inHAIs,
      and determine the risk factors associated with HAIs and all-cause mortalityat
      selected hospitals in Thailand. A survey with a total time frame of 10 days
      wasconducted at selected 50 hospitals across Thailand during January 2014: 19
      primarygovernment hospitals, 15 secondary government hospitals, 13 tertiary
      governmenthospitals, 2 private hospitals and 1 government university hospital. Of
      15,475 casesreviewed, 688 patients had 791 HAIs (1.1 HAI per infected patient).
      The rate ofHAI was 4.4% (95%CI: 4.1-4.8): 7.3% (95%CI: 4.6-9.3) at the university
      hospitalsurveyed, 5.0% (95%CI: 4.6-5.4) at the tertiary hospitals surveyed, 3.9%
      (95%CI:3.4-4.6) at the secondary hospitals surveyed, 2.0% (95%CI: 1.3-2.7) at the
      primaryhospitals surveyed, and 1.6% (95%CI: 0.5-2.8) at the private hospitals
      surveyed.The ward with the frequent number of HAI was the intensive care unit
      (17%). Thetwo most commonly affected age ranges were those aged >60 years and <1
      year.Of the 791 HAIs found in this survey, the 3 most frequently reported types
      of HAIwere: respiratory tract infections (n=377, 48%), urinary tract infections
      (n=176,22%) and surgical site infections (n=55, 7%). Of the 688 patients with a
      HAI, 24%died within three months of this survey. The most frequently reported
      bacterialpathogen was Acinetobacter species (17%). On multivariate analysis, HAIs
      weresignificantly associated with patient age <1 year, a university hospital,
      havingmajor surgery, urinary catheterization, being on a respiratory ventilator,
      havinga tracheostomy, and having central venous catheterization (p <0.05). Death
      wasassociated with patient age <1 year, a university hospital, being on a
      surgicalor medical ward, being on a ventilator, and having a central venous
      catheter (p<0.05). HAIs are major public health problems in the studied hospitals
      and resultin substantial mortality.

PMID- 29644842
TI  - ITO-TiN-ITO Sandwiches for Near-Infrared Plasmonic Materials.
AB  - Indium tin oxide (ITO)-based sandwich structures with the insertion of ultrathin
      (<10 nm) titanium nitride (TiN) are investigated as near-infrared (NIR) plasmonic
      materials. The structural, electrical, and optical properties reveal the
      improvement of the sandwich structures stemmed from TiN insertion. TiN is a well
      established alternative to noble metals such as gold, elevating the electron
      conductivity of sandwich structures as its thickness increases. Dielectric
      permittivities of TiN and top ITO layers show TiN-thickness-dependent properties,
      which lead to moderate and tunable effective permittivities for the sandwiches.
      The surface plasmon polaritons (SPP) of the ITO-TiN-ITO sandwich at the
      telecommunication window (1480-1570 nm) are activated by prism coupling using
      Kretschmann configuration. Compared with pure ITO films or sandwiches with metal
      insertion, the reflectivity dip for sandwiches with TiN is relatively deeper and
      wider, indicating the enhanced coupling ability in plasmonic materials for
      telecommunications. The SPP spatial profile, penetration depth, and degree of
      confinement, as well as the quality factors, demonstrate the applicability of
      such sandwiches for NIR plasmonic materials in various devices.

PMID- 29644843
TI  - Noncovalently Assembled Electroconductive Hydrogel.
AB  - Cross-linking biomolecules with electroconductive nanostructures through
      noncovalent interactions can result in modular networks with defined biological
      functions and physical properties such as electric conductivity and
      viscoelasticity. Moreover, the resulting matrices can exhibit interesting
      features caused by the dynamic assembly process, such as self-healing and
      molecular ordering. In this paper, we present a physical hydrogel system formed
      by mixing peptide-polyethylene glycol and poly(3,4
      ethylenedioxythiophene):polystyrene sulfonate. This combinatorial approach, which
      uses different modular building blocks, could lead to high tunability on aspects
      of rheology and electrical impedance. The proposed physical hydrogel system is
      characterized by both a self-healing ability and injectability. Interestingly,
      the formation of hydrogels at relatively low concentrations led to a network of
      closer molecular packing of poly(3,4-ethylenedioxythiophene) nanoparticles,
      reflected by the enhanced conductivity. The biopolymer system can be used to
      develop three-dimensional cell cultures with incorporated electric stimuli, as
      evidenced by its contribution to the survival and proliferation of encapsulated
      mesenchymal stromal cells and their differentiation upon electrical stimulation.

PMID- 29644844
TI  - Iterative Synthetic Strategy for Azaphenalene Alkaloids. Total Synthesis of (-)
      9a epi-Hippocasine.
AB  - A new strategy for the stereoselective synthesis of alkaloids with perhydro-9b
      azaphenalene skeleton has been developed. The starting material is the
      substituted glutarimide derivative 1, readily available in either enantiomeric
      form through the palladium-catalyzed asymmetric allylic alkylation of
      glutarimide. The strategy relies on an iterative methodology encompassing two
      nucleophilic allylations and two ring closing metathesis processes. The approach
      has been used in the first synthesis of (-)-9a- epi-hippocasine.

PMID- 29644845
TI  - Robust Hydrogels from Lanthanide Nucleotide Coordination with Evolving
      Nanostructures for a Highly Stable Protein Encapsulation.
AB  - Metal coordination with organic ligands often produce crystalline metal-organic
      frameworks and sometimes amorphous nanoparticles. In this work, we explore a
      different type of material from the same chemistry: hydrogels. Lanthanides are
      chosen as the metal component because of their important technological
      applications and continuously tunable properties. Adenosine monophosphate (AMP)
      and lanthanides form two types of coordination materials: the lighter lanthanides
      from La3+ to Tb3+ form nanoparticles, whereas the rest heavier ones initially
      form nanoparticles but later spontaneously transform to hydrogels. This slow sol
      to-gel transition is accompanied by heat release, as indicated by isothermal
      titration calorimetry. The transition is also accompanied by a morphology change
      from nanoparticles to nanofibers, as indicated by transmission electron
      microscopy. These gels are insensitive to ionic strength or temperature with
      excellent stability. Gelation is unique to AMP because other nucleotides or other
      adenine derivatives only yield nanoparticles or soluble products. Entrapment of
      guest molecules such as glucose oxidase is also explored, where the hydrogels
      allow a better enzyme activity and stability compared to nanoparticles. Further
      applications of lanthanide coordinated hydrogels might include biosensors,
      imaging agents, and drug delivery.

PMID- 29644846
TI  - Site-Selective Benzannulation of N-Heterocycles in Bidentate Ligands Leads to
      Blue-Shifted Emission from [( P^N)Cu]2(MU-X)2 Dimers.
AB  - Benzannulated bidentate pyridine/phosphine ( P^N) ligands bearing quinoline or
      phenanthridine (3,4-benzoquinoline) units have been prepared, along with their
      halide-bridged, dimeric Cu(I) complexes of the form [( P^N)Cu]2(MU-X)2. The
      copper complexes are phosphorescent in the orange-red region of the spectrum in
      the solid-state under ambient conditions. Structural characterization in solution
      and the solid-state reveals a flexible conformational landscape, with both
      diamond-like and butterfly motifs available to the Cu2X2 cores. Comparing the
      photophysical properties of complexes of (quinolinyl)phosphine ligands with those
      of pi-extended (phenanthridinyl)phosphines has revealed a counterintuitive impact
      of site-selective benzannulation. Contrary to conventional assumptions regarding
      pi-extension and a bathochromic shift in the lowest energy absorption maxima, a
      blue shift of nearly 40 nm in the emission wavelength is observed for the
      complexes with larger ligand pi-systems, which is assigned as phosphorescence on
      the basis of emission energies and lifetimes. Comparison of the ground-state and
      triplet excited state structures optimized from DFT and TD-DFT calculations
      allows attribution of this effect to a greater rigidity for the benzannulated
      complexes resulting in a higher energy emissive triplet state, rather than
      significant perturbation of orbital energies. This study reveals that ligand
      structure can impact photophysical properties for emissive molecules by
      influencing their structural rigidity, in addition to their electronic structure.

PMID- 29644847
TI  - Preparation of Microkernel-Based Mesoporous (SiO2-CdTe-SiO2)@SiO2 Fluorescent
      Nanoparticles for Imaging Screening and Enrichment of Heat Shock Protein 90
      Inhibitors from Tripterygium Wilfordii.
AB  - The currently utilized ligand fishing for bioactive molecular screening from
      complex matrixes cannot perform imaging screening. Here, we developed a new solid
      phase ligand fishing coupled with an in situ imaging protocol for the specific
      enrichment and identification of heat shock protein 90 (Hsp 90) inhibitors from
      Tripterygium wilfordii, utilizing a multiple-layer and microkernel-based
      mesoporous nanostructure composed of a protective silica coating CdTe quantum dot
      (QD) core and a mesoporous silica shell, i.e., microkernel-based mesoporous (SiO2
      CdTe-SiO2)@SiO2 fluorescent nanoparticles (MMFNPs) as extracting carries and
      fluorescent probes. The prepared MMFNPs showed a highly uniform spherical
      morphology, retention of fluorescence emission, and great chemical stability. The
      fished ligands by Hsp 90alpha-MMFNPs were evaluated via the preliminary
      bioactivity based on real-time cellular morphology imaging by confocal laser
      scanning microscopy (CLSM) and then identified by mass spectrometry (MS).
      Celastrol was successfully isolated as an Hsp 90 inhibitor, and two other
      specific components screened by Hsp 90alpha-MMFNPs, i.e., demecolcine and
      wilforine, were preliminarily identified as potential Hsp 90 inhibitors through
      the verification of strong affinity to Hsp 90 and antitumor bioactivity. The
      approach based on the MMFNPs provides a strong platform for imaging screening and
      discovery of plant-derived biologically active molecules with high efficiency and
      selectivity.

PMID- 29644848
TI  - Preparation of N-Graphdiyne Nanosheets at Liquid/Liquid Interface for
      Photocatalytic NADH Regeneration.
AB  - Two-dimensional (2D) N-graphdiyne (N-GDY) nanosheets containing different number
      of N were synthesized by polymerization of triazine, pyrazine, and pyridine-based
      monomers at liquid/liquid interface. The configurations and nanostructures of N
      GDY were well-characterized. The wettability changed to more hydrophilic as the N
      contents increased. The collected N-GDY was further employed as metal-free
      photocatalyst for NADH regeneration. The catalytic performance was related with
      the N content in the graphdiyne. The N3-GDY demonstrated the best activity. This
      strategy provided a new promising platform of designing unique 2D N-GDY with
      tunable performance in biorelated catalysis.

PMID- 29644849
TI  - Concurrent Cooperative J-Aggregates and Anticooperative H-Aggregates.
AB  - Completely understanding the working mechanisms of sophisticated supramolecular
      self-assembly exhibiting competing paths is very important for chemists en route
      to acquiring the ability of constructing supramolecular systems with controlled
      structures and designed functions. Here, the self-aggregation behaviors of an N
      heterocyclic aromatic dicarboximide molecule 1, boasting two competing paths that
      give rise to different supramolecular structures and exhibit distinct
      thermodynamic features, are carefully examined. First, a group of H-aggregates
      are observed when providing a medium driving force for aromatic stacking, and
      their formation is manifested as an anticooperative process. When exposed to
      enhanced strength of aromatic interactions, these H-aggregates are found to
      transform into J-aggregates via a cooperative assembly mechanism. With the
      assistance of a mathematic model accommodating two competing polymerization
      pathways, calculations are conducted to simulate and explain the thermodynamic
      equilibria of such a unique supramolecular system. The calculation results are
      highly consistent with the experimental observations, and some important
      properties are elucidated. Specifically, the anticooperative assembly mechanism
      generally promotes the formation of low to medium oligomers, whereas the
      cooperative path is more competent at producing high polymers. If the
      anticooperative and cooperative routes coexist and compete for the same molecule,
      the cooperative formations of high polymers are significantly suppressed unless a
      very high degree of polymerization can be achieved. Such a unique feature of
      concurring anticooperative and cooperative paths emerges to the H- and J
      aggregates of molecule 1 and thus brings about the interesting sequential
      appearances of the two types of aggregates under conditions of continuously
      enlarged driving force for self-aggregation. Finally, based on the knowledge
      acquired from this study and by analyzing the steric features of 1 that influence
      its supramolecular packing motifs, a slightly modified molecular structure is
      designed, with which the intermediate H-aggregation state was successfully
      suppressed, and a single cooperative J-aggregation path is manifested.

PMID- 29644850
TI  - The Role of Phase Separation in Heterochromatin Formation, Function, and
      Regulation.
AB  - In eukaryotic cells, structures called heterochromatin play critical roles in
      nuclear processes ranging from gene repression to chromosome segregation.
      Biochemical and in vivo studies over the past several decades have implied that
      the diverse functions of heterochromatin rely on the ability of these structures
      to spread across large regions of the genome, to compact the underlying DNA, and
      to recruit different types of activities. Recent observations have suggested that
      heterochromatin may possess liquid droplet-like properties. Here, we discuss how
      these observations provide a new perspective on the mechanisms for the assembly,
      regulation, and functions of heterochromatin.

PMID- 29644851
TI  - Formal Total Synthesis of Actinoranone: Synthesis Approaches and Cytotoxic
      Studies.
AB  - This article describes our efforts toward the total synthesis of actinoranone.
      Our synthesis strategies rely on a convergent route to connect the terpenoid and
      polyketide fragments, employing catalysis and powerful classical reactions for
      the assembly of these key fragments. A new transformation was disclosed during
      this work, a domino ring-opening and esterification. Initial cytotoxic studies
      for the selected synthesis intermediates are also presented.

PMID- 29644852
TI  - Improving the Organoleptic Properties of a Craft Mezcal Beverage by Increasing
      Fatty Acid Ethyl Ester Contents through ATF1 Expression in an Engineered
      Kluyveromyces marxianus UMPe-1 Yeast.
AB  - Mezcal, a traditional beverage that originated in Mexico, is produced from
      species of the Agavaceae family. The esters associated with the yeasts utilized
      during fermentation are important for improving the organoleptic properties of
      the beverage. We improved the ester contents in a mezcal beverage by using the
      yeast Kluyveromyces marxianus, which was engineered with the ATF1 gene. ATF1
      expression in the recombinant yeast significantly increased compared with that in
      the parental yeast, but its fermentative parameters were unchanged. Volatile
      organic-compound-content analysis showed that esters had significantly increased
      in the mezcal produced with the engineered yeast. In a sensory-panel test, 48% of
      the panelists preferred the mezcal produced from the engineered yeast, 30%
      preferred the mezcal produced from the wild type, and 15 and 7% preferred the two
      mezcal types produced following the routine procedure. Correlation analysis
      showed that the fruitiness/sweetness description of the mezcal produced using the
      ATF1-engineered K. marxianus yeast correlated with the content of the esters,
      whose presence improved the organoleptic properties of the craft mezcal beverage.

PMID- 29644853
TI  - Site-Specific Functionalization of 1,3-Dioxolane with Imines: A Radical Chain
      Approach to Masked alpha-Amino Aldehydes.
AB  - A thiol-promoted site-specific addition of 1,3-dioxolane to imines through a
      radical chain process is described. This process represents a metal-free and
      redox-neutral way to convert inexpensive materials to a broad range of protected
      alpha-amino aldehydes in good to excellent yields using only a catalytic amount
      of radical precursor. Control experiments revealed that both the thiol and a
      small amount of oxygen from air are indispensable to the success of this
      reaction.

PMID- 29644854
TI  - Well-Dispersed Ruthenium in Mesoporous Crystal TiO2 as an Advanced
      Electrocatalyst for Hydrogen Evolution Reaction.
AB  - TiO2 mesoporous crystal has been prepared by one-step corroding process via an
      oriented attachment (OA) mechanism with SrTiO3 as precursor. High resolution
      transmission electron microscopy (HRTEM) and nitrogen adsorption-desorption
      isotherms confirm its mesoporous crystal structure. Well-dispersed ruthenium (Ru)
      in the mesoporous nanocrystal TiO2 can be attained by the same process using Ru
      doped precursor SrTi1- xRu xO3. Ru is doped into lattice of TiO2, which is
      identified by HRTEM and super energy dispersive spectrometer (super-EDS)
      elemental mapping. X-ray photoelectron spectroscopy (XPS) and electron
      paramagnetic resonance spectroscopy (EPR) suggest the pentavalent Ru but not
      tetravalent, while partial Ti in TiO2 accept an electron from Ru and become Ti3+,
      which is observed for the first time. This Ru-doped TiO2 performs high activity
      for electrocatalytic hydrogen evolution reaction (HER) in alkaline solution.
      First-principles calculations simulate the HER process and prove TiO2:Ru with
      Ru5+ and Ti3+ holds high HER activity with appropriate hydrogen-adsorption Gibbs
      free energies (Delta GH).

PMID- 29644856
TI  - Photoinduced Reactions of Benzophenone in Biaxially Oriented Polypropylene.
AB  - The photoinduced reactions of benzophenone (B) in biaxially oriented
      polypropylene (BOPP) were studied with nanosecond laser photolysis (N2 laser,
      lambda337.1 nm). The first observed transient was a triplet state 3B*. Decay of
      3B* led to formation of a radical pair (RP) of BH* and R*, where R* is a radical
      formed by hydrogen abstraction from BOPP (RH) by 3B*. We studied BOPP after the
      preheating for a short time in a temperature range 298-423 K, which is
      essentially lower than its melting point of 453 K. All measurements with not
      heated and with preheated (annealed) BOPP were made at 298 K. A radical pair (RP)
      apparently decays as a contact pair 3[BH*, R*] in nonheated BOPP. A critical
      phenomenon takes place: dissociation of RP with a formation of free radicals in
      the polymer bulk is observed at preheating temperature Tcrit ~ 403 K and at a
      higher T. The physical process of heating and cooling of BOPP apparently resulted
      in the restructuring of crystallites, their agglomeration, shrinking of the
      distribution of crystallites according to their sizes in BOPP. Overall BOPP
      becomes softer which manifests itself in the radical kinetics. The decay kinetics
      of 3B* and RP in the cage fits well the first-order law. Rate constants were
      obtained. Radicals BH*, which exit into the polymer bulk at temperatures of
      preheating T >= 403 K, decay by cross-termination according to the second-order
      law. A relatively high rate constant ~108 M-1.s-1 for this reaction was obtained
      due to diffusion of BH* enclosed in the soft amorphous phase of BOPP. Properties
      of BOPP containing B were studied with ESR, DSC, IR, and WAXD.

PMID- 29644855
TI  - Porphyrin-Oligopyridine Triads: Synthesis and Optical Properties.
AB  - The synthesis of two triads with two porphyrinyl units linked by oligopyridine
      derivatives and a new beta-functionalized porphyrin-dihydroazepine is described.
      One of the porphyrin-oligopyridine triads has a quinquepyridine unit connecting
      the porphyrins beta-pyrrolic positions, while the other one has an asymmetric
      quaterpyridine with one of the pyridines fused to the porphyrin. All compounds
      have fluorescence emission quantum yields in the range of meso
      tetraphenylporphyrin (16-22%).

PMID- 29644857
TI  - Catalytic Phosphite Hydrolysis under Neutral Reaction Conditions.
AB  - Cationic phosphametallocene-based platinum(II) aqua complexes were used as
      efficient precatalysts for the hydrolysis of aromatic and aliphatic tertiary
      phosphites under neutral reaction conditions at room temperature, leading to the
      selective cleavage of one P-O bond of the phosphite. NMR labeling experiments
      combined with stoichiometric model reactions and theoretical density functional
      theory calculations, performed with the appropriate model compounds, shed light
      on the operative catalytic cycle, which comprises intramolecular water molecule
      transfer to the cis-coordinated phosphite molecule.

PMID- 29644858
TI  - Importance of Molecular Meshing for the Stabilization of Solvophobic Assemblies.
AB  - The effect of the methyl groups in neutral gear-shaped amphiphiles (GSAs) on the
      stability of nanocubes was investigated using a novel C2 v-symmetric GSA, which
      was synthesized using selective alternate trilithiation of a pentabrominated
      hexaphenylbenzene derivative. The lack of only one methyl group in the GSA
      decreased the association constant for the assembly of the nanocube by 3 orders
      of magnitude. A surface analysis recently developed by the authors (SAVPR:
      surface analysis with varying probe radii) was carried out for characteristic
      isomers of the nanocube consisting of C2 v-symmetric GSAs. It was found that the
      methyl groups near the equator of the nanocube play a significant role in the
      stabilization of the nanocubes.

PMID- 29644859
TI  - The Application of 2-Benzyl-1,4-naphthoquinones as Pronucleophiles in
      Aminocatalytic Synthesis of Tricyclic Derivatives.
AB  - This study demonstrates an unprecedented reactivity of 2-substituted-1,4
      naphthoquinones. By applying the principle of vinylogy, they have been employed
      as vinylogous pronucleophiles in the organocatalytic cascade reaction for the
      first time. This novel catalytic activation of 1,4-naphthoquinones enables access
      to carboannulated naphthalen-1(4 H)-one derivatives of biological importance. The
      site-selectivity and stereoselectivity of a process proved possible to control by
      the proper choice of reaction conditions.

PMID- 29644860
TI  - Up-Regulation of T-Cell Activation MicroRNAs in Drug-Specific CD4+ T-Cells from
      Hypersensitive Patients.
AB  - Dysregulation in the expression of microRNAs (miRNAs), single-stranded RNAs which
      regulate gene expression, has been associated with diseases such as Stevens
      Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), although their cellular
      origin has not been explored. Thus, the focus of this work was to study
      expression patterns of reported miRNAs involved in T-cell activation following
      drug-specific stimulation in peripheral blood mononuclear cells (PBMCs) and drug
      specific CD4+ T-cell clones (TCC) from patients with different cutaneous
      manifestations of delayed-type drug hypersensitivity reactions. CD4+ T-cells from
      hypersensitive patients were stimulated to proliferate, secreted cytokines (IFN
      gamma and IL-22), cytolytic molecules (Granzyme B) and up-regulate miRNAs 24 to
      48 h after drug exposure. Carbamazepine-specific CD4+ T-cells that proliferated
      to the greatest extent and secreted the highest levels of IFN-gamma showed an up
      regulation of miR-18a and miR-155. In contrast, piperacillin-specific CD4+ T
      cells displaying high expression of miR-9 and miR-21 showed an association with
      the extent of proliferation, but not IFN-gamma secretion. MiR-155 up-regulation
      was detected in PBMCs from all hypersensitive patients 24 h after drug treatment,
      while miR-18a and miR-21 expression was up-regulated after 48 h. These findings
      demonstrate that miRNAs are expressed during drug-specific CD4+ T-cell activation
      and shows a new regulation path for drug hypersensitivity reactions.

PMID- 29644861
TI  - Cyclic-Voltammetry-Based Solid-State Gas Sensor for Methane and Other VOC
      Detection.
AB  - We present the fabrication, characterization, and testing of an electrochemical
      volatile organic compound (VOC) sensor operating in gaseous conditions at room
      temperature. It is designed to be microfabricated and to prove the sensing
      principle based on cyclic voltammetry (CV). It is composed of a working electrode
      (WE), a counter electrode (CE), a reference electrode (RE), and a Nafion solid
      state electrolyte. Nafion is a polymer that conducts protons (H+) generated from
      redox reactions from the WE to the CE. The sensor needs to be activated prior to
      exposure to gases, which consists of hydrating the Nafion layer to enable its ion
      conduction properties. During testing, we have shown that our sensor is not only
      capable of detecting methane, but it can also quantify its concentration in the
      gas flow as well as differentiate its signal from carbon monoxide (CO). These
      results have been confirmed by exposing the sensor to two different
      concentrations of methane (50% and 10% of methane diluted in N2), as well as pure
      CO. Although the signal is positioned in the Hads region of Pt, because of
      thermodynamic reasons it cannot be directly attributed to methane oxidation into
      CO2. However, its consistency suggests the presence of a methane-related
      oxidation process that can be used for detection, identification, and
      quantification purposes.

PMID- 29644862
TI  - Direct ortho-Selective Amination of 2-Naphthol and Its Analogues with Hydrazines.
AB  - Described herein is a regioselective ortho-amination of 2-naphthol and its
      analogues with substituted hydrazines. It provides a direct methodology for the
      synthesis of N-arylaminated naphthol derivatives without the formation of related
      1,1'-biaryl-2,2'-diamine or carbazole byproducts. Specifically, using N, N
      disubstituted hydrazine precursors, N-unsubstituted ortho-aminated derivatives
      and related secondary amines can be formed in ethylene glycol in moderate to
      excellent yields. Variation of substrates to N, N'-diarylhydrazines and N-methyl-
      N, N'-diarylhydrazines led to N-aryl-1-amino-2-naphthol compounds. It is noted
      that biologically interesting indazole motifs can be facilely created by the
      reaction of N, N'-dialkylhydrazines with 2-naphthols. These ortho-amination
      reactions have the advantage of one-pot operation without the use of transition
      metal catalysts.

PMID- 29644863
TI  - Reversible Cation-Selective Attachment and Self-Assembly of Human Tau on
      Supported Brain Lipid Membranes.
AB  - Misfolding and aggregation of the neuronal, microtubule-associated protein tau is
      involved in the pathogenesis of Alzheimer's disease and tauopathies. It has been
      proposed that neuronal membranes could play a role in tau release,
      internalization, and aggregation and that tau aggregates could exert toxicity via
      membrane permeabilization. Whether and how tau interacts with lipid membranes
      remains a matter of discussion. Here, we characterize the interaction of full
      length human tau (htau40) with supported lipid membranes (SLMs) made from brain
      total lipid extract by time-lapse high-resolution atomic force microscopy (AFM).
      We observe that tau attaches to brain lipid membranes where it self-assembles in
      a cation-dependent manner. Sodium triggers the attachment, self-assembly, and
      growth, whereas potassium inhibits these processes. Moreover, tau assemblies are
      stable in the presence of sodium and lithium but disassemble in the presence of
      potassium and rubidium. Whereas the pseudorepeat domains (R1-R4) of htau40
      promote the sodium-dependent attachment to the membrane and stabilize the tau
      assemblies, the N-terminal region promotes tau self-assembly and growth.

PMID- 29644864
TI  - Hot Biexciton Effect on Optical Gain in CsPbI3 Perovskite Nanocrystals.
AB  - Combining the superior optical properties of their bulk counterparts with quantum
      confinement effects, lead halide perovskite nanocrystals are unique laser
      materials with low-threshold optical gain. In such nonlinear optical regimes,
      multiple excitons are generated in the nanocrystals and strongly affect the
      optical gain through many-body interactions. Here, we investigate the exciton
      exciton interactions in CsPbI3 nanocrystals by femtosecond transient absorption
      spectroscopy. From the analysis of the induced absorption signal observed
      immediately after the pump excitation, we estimated the binding energy for the
      hot biexcitons that are composed of an exciton at the band edge and a hot exciton
      generated by the pump pulse. We found that the exciton-exciton interaction
      becomes stronger for hot excitons with greater excess energies and that the
      optical gain can be controlled by changing the excess energy of the hot excitons.

PMID- 29644865
TI  - Thermal-Induced Dielectric Switching with 40K Wide Hysteresis Loop Near Room
      Temperature.
AB  - A thermal-induced dielectric switching has been realized in two ion-pair crystal
      [C2H6N5]+.[H2PO4]- (1, C2H6N5 = 3,5-diamino-1,2,4-triazolinium) through single
      crystal-to-single-crystal phase transition (SCSC-PT). Upon cooling from room
      temperature, the 1D cation stripes that are composed of [C2H5N5]+ cations have
      undergone a 90 degrees  sharp rotation around the c axis, accompanied by the
      transition of crystal stacking from loose unparallel (dynamic state) to
      compression parallel (static state) and reorientation of dipoles on the [C2H5N5]+
      cation, which thus resulted in high dielectric state to low dielectric state
      transformation. While on the warming run, the reverse process was rather
      sluggish, resulting in a reversible dielectric switching with ultralarge (about
      40K wide) hysteresis loop near room temperature. It is thought that the large
      sized polar cation stripes have a predominant influence on the switching
      properties of 1.

PMID- 29644866
TI  - Diagnostic Accuracy of Symptoms, Endoscopy, and Imaging Signs of Chronic
      Rhinosinusitis Without Nasal Polyps Compared to Allergic Rhinitis.
AB  - Objectives The diagnosis of chronic rhinosinusitis without nasal polyps (CRSsNP)
      and distinguishing it from allergic rhinitis is difficult. Yet, early detection
      of CRSsNP is important to prevent progressive and severe chronic rhinosinusitis.
      Our aim was to compare diagnostic accuracy of symptoms, endoscopy, and imaging
      signs of CRSsNP and allergic rhinitis -only phenotypes. Setting Prospective
      controlled follow-up study. Participants Forty-two nonsmoking patients visiting
      tertiary care due to CRSsNP and 19 nonsmoking volunteer controls with allergic
      rhinitis filled a symptoms questionnaire and underwent nasal endoscopy off
      seasonally. All CRSsNP patients underwent computed tomography scans of paranasal
      sinuses. All the allergic rhinitis control subjects and 14 of the CRSsNP patients
      underwent sinus magnetic resonance imaging. Results Radiologic Lund-Mackay score,
      duration of symptoms, visual analogue scale scores of symptoms, and Sinonasal
      Outcome Test 22 were significantly higher in the CRSsNP group compared to
      allergic rhinitis control group. These factors also correlated in part with each
      other. Endoscopic score did not correlate with other factors, nor did it differ
      between CRSsNP and allergic rhinitis groups. The highest area under curve value
      was demonstrated for visual analogue scale score of facial pain/pressure (0.93)
      and score >=4/10 showed 60% sensitivity and 95% specificity for detecting CRSsNP
      group ( P < .001). Radiologic sign of obstructed osteomeatal complex showed 100%
      specificity and 38% sensitivity for detecting CRSsNP group ( P < .001).
      Conclusions CRSsNP phenotype could be primarily distinguished from allergic
      rhinitis by higher facial pain/pressure score and secondarily by radiologic sings
      of obstructed ostiomeatal complex and higher Lund-Mackay score. Endoscopic score
      has limited value in distinguishing CRSsNP from allergic rhinitis.

PMID- 29644867
TI  - Ultrasonically controlled estrone-modified liposomes for estrogen-positive breast
      cancer therapy.
AB  - A new modality of drug targeting to tumors has been proposed. The ligand-mediated
      approach, that already increases the therapeutic index of the drug, can still be
      optimized by the encapsulation of the drug into sonosensitive nanoparticles. In
      this work, an endogenous ligand, estrone, was used to synthesize doxorubicin
      encapsulating liposomes for estrogen receptor (ER)-positive breast cancer therapy
      with cyanuric chloride (2,4,6 trichloro-1,3,5 triazine) being used as a linking
      molecule to attach 3-OH group of estrone to the surface of liposomes. Then, drug
      release from liposomes was studied using ultrasound waves as a triggering
      mechanism with different frequencies and power densities. In addition, drug
      uptake by two cell lines ER-positive (MCF-7) and ER-negative (MDA-MB-231) was
      assessed, with the former cell line being examined later to study the synergetic
      effect of the receptor mediator targeting and ultrasound trigger. The sizes of
      the liposomes loaded with calcein (as a doxorubicin model drug) were determined
      by dynamic light scattering, and they were characterized as large unilamellar
      vesicles (LUVs). The release from the prepared liposomes triggered by ultrasound
      (US) waves at low frequency (20 kHz) and high frequency (1.07 and 3.24 MHz), at
      several power densities, was determined by monitoring the changes in calcein
      fluorescence, using a spectrofluorometer. Increasing power densities showed a
      significant effect on release at high frequencies and during the first two US
      pulses at low frequency. The echogenicity of the liposomes was proven and
      characterized at different power densities and frequencies. To confirm the
      viability of the carrier as a doxorubicin carrier, doxorubicin-encapsulating
      liposomes were prepared using the ammonium sulfate transmembrane gradient method.
      The liposomes were LUVs and were US-sensitive, exhibiting similar behavior to
      calcein-encapsulating liposomes. The calcein uptake by an ER + cell line (MCF-7)
      was compared with the uptake by an ER-cell line (MDA-MB-231). The MCF-7 uptake
      was significantly higher than the MDA-MB-231 uptake, which proved the targeting
      potential of estrone-conjugated liposomes. The exposure to low-frequency
      ultrasound (LFUS) revealed a statistically significant uptake of calcein compared
      to uptake without ultrasound. The described drug delivery (DD) system, comprising
      a new echogenic liposomal formulation, promises a non-immunogenic and site
      specific biomedical approach to ER-positive breast cancer therapy.

PMID- 29644868
TI  - CRISPR/Cas9 Inhibits Multiple Steps of HIV-1 Infection.
AB  - CRISPR/Cas9 is an adaptive immune system where bacteria and archaea have evolved
      to resist the invading viruses and plasmid DNA by creating site-specific double
      strand breaks in DNA. This study tested this gene editing system in inhibiting
      human immunodeficiency virus type 1 (HIV-1) infection by targeting the viral long
      terminal repeat and the gene coding sequences. Strong inhibition of HIV-1
      infection by Cas9/gRNA was observed, which resulted not only from insertions and
      deletions (indels) that were introduced into viral DNA due to Cas9 cleavage, but
      also from the marked decrease in the levels of the late viral DNA products and
      the integrated viral DNA. This latter defect might have reflected the degradation
      of viral DNA that has not been immediately repaired after Cas9 cleavage. It was
      further observed that Cas9, when solely located in the cytoplasm, inhibits HIV-1
      as strongly as the nuclear Cas9, except that the cytoplasmic Cas9 does not act on
      the integrated HIV-1 DNA and thus cannot be used to excise the latent provirus.
      Together, the results suggest that Cas9/gRNA is able to target and edit HIV-1 DNA
      both in the cytoplasm and in the nucleus. The inhibitory effect of Cas9 on HIV-1
      is attributed to both the indels in viral DNA and the reduction in the levels of
      viral DNA.

PMID- 29644869
TI  - Pearls and pitfalls in imaging of blunt traumatic thoracic aortic injury: a
      pictorial review.
AB  - Blunt thoracic aortic injury (TAI) occurs most frequently as a sequelae of high
      impact deceleration such as high-velocity road traffic accidents and falls from
      height. The burden of mortality and morbidity is high, however advances in pre
      hospital care, diagnostic imaging and endovascular therapies have improved
      outcomes in this group of patients. Emergent treatment depends on accurate, early
      diagnosis by the radiologist. It is therefore of paramount importance that
      radiologists are familiar with both the direct (intimal flap, pseudoaneurysm,
      aortic contour irregularity and contrast extravasation) and indirect (periaortic
      haematoma) imaging findings of TAI. Furthermore, it is critical that technical
      (breathing artefact and cardiac motion artefact) as well as anatomical (ductus
      diverticulum, aortic spindle and mediastinal structures which imitate periaortic
      haematoma) pitfalls are recognised to avoid misdiagnosis. This pictorial review
      will help the diagnostic radiologist to recognise the patterns of injury and
      imaging features associated with TAI, as well as highlighting potential mimics
      when interrogating CTangiography (CTA) in major trauma.

PMID- 29644870
TI  - A novel polyphenolic prebiotic and probiotic formulation have synergistic effects
      on the gut microbiota influencing Drosophila melanogaster physiology.
AB  - The gut microbiota is a vast community of synergistic bacterial species providing
      health benefits to the host. Imbalances in the gut microbiota (dysbiosis) due to
      diet, antibiotic use, age and stress contribute to disease development including
      diabetes, obesity, colon cancer, inflammatory bowel disease, inflammaging and
      neurodegeneration. Fortunately, a probiotic regime with a diet rich in prebiotics
      may reverse dysbiosis promoting health and wellness in age. The current study
      designs, optimizes and tests a novel probiotic and synbiotic formulation
      consisting of three metabolically active probiotics Lactobacillus plantarum,
      Lactobacillus fermentum and Bifidobacteria infantis together with a novel
      polyphenol-rich prebiotic, Triphala. The prebiotic action of Triphala was
      characterized using in vitro batch cultures, Drosophila melanogaster and a
      simulated model of the human gastrointestinal tract (SHIME) where in each model,
      Triphala supported growth of beneficial bacteria while inhibiting pathogenic
      species. Neither Triphala at 0.5% w/v nor the individual probiotics at 5.0 * 108
      to 7.5 * 109 CFU/ml demonstrated toxicity in Drosophila. Interestingly, motility
      was combinatorially enhanced by the probiotic and synbiotic formulations
      reflecting the beneficial variations in the gut microbiota. Altogether, the
      present study shows that probiotics and synbiotics in combination are more
      effective at modulating the gut microbiota and eliciting biological effects than
      their components.

PMID- 29644871
TI  - Interprofessional Rounds Improve Timing of Appropriate Palliative Care
      Consultation on a Hospitalist Service.
AB  - Despite known benefits, palliative care (PC) consultation for hospitalized
      patients remains underutilized. The objective was to improve frequency and
      timeliness of appropriate inpatient PC consultation. On 2 of 11 hospitalist
      teams, a PC representative attended discharge rounds twice a week. Control teams'
      discharge rounds were unenhanced. Subjects were all patients admitted to a
      hospitalist service in a quaternary academic medical center. The primary outcome
      was change in provision of PC consultation over time; the secondary outcome was
      change in time-to-consult (days). Hospitalists were surveyed regarding the
      intervention. The unadjusted proportion of patients receiving PC consultation
      increased from 2.7% to 5.2% on the intervention teams. Compared to control teams
      over time and adjusting for multiple covariates, the intervention increased PC
      consultation (difference-in-difference [DID] = 1.0 percentage-point increase [95%
      CI = 0.3%-1.8%]) and decreased time to consult (DID = -5 days [95% CI = -11 to 
      1]) in patients admitted for noncancer diagnoses. Hospitalists thought the
      intervention facilitated effective patient care without increased burden.

PMID- 29644872
TI  - Harnessing the Power of Peer Influence to Improve Quality.

PMID- 29644873
TI  - Social Media and New Technology: A Primer.
AB  - Social media and new media are becoming increasingly important in the lives of
      preteens and teens. This article reviews what is currently known about positive
      and negative effects of social media, social networking, and internet use and
      what safety measures should be considered.

PMID- 29644874
TI  - Impact of a "No Mobile Device" Policy on Developmental Surveillance in a
      Pediatric Clinic.
AB  - Children commonly use mobile devices at pediatric office visits. This practice
      may affect patient-provider interaction and undermine accuracy of developmental
      surveillance. A randomized, provider-blinded, controlled trial examined whether a
      policy prohibiting mobile device use in a pediatric clinic improved accuracy of
      pediatricians' developmental surveillance. Children, aged 18 to 36 months, were
      randomized to device-prohibited (intervention; n = 58) or device-allowed
      (control; n = 54) groups. After a 30-minute well-visit, development was evaluated
      as "normal," "borderline," or "delayed" in 5 categories using the Ages and Stages
      Questionnaire (ASQ-3). ASQ-3 results were compared with providers' clinical
      assessment in each category. Provider-ASQ discrepancies were more common for
      intervention participants ( P = .025). Providers "missed" more ASQ-3 "delayed"
      scores ( P = .005) in the intervention group, particularly in the fine motor
      domain ( P = .018). Prohibiting mobile device use at well-visits did not improve
      accuracy of providers' developmental surveillance. Mobile devices may entertain
      children at well-visits, allowing opportunities for parent-provider discussion,
      or observation of fine motor skills.

PMID- 29644875
TI  - A Single Intra-Articular Injection of Gel-200 for Treatment of Symptomatic
      Osteoarthritis of the Knee Is More Effective than Phosphate Buffered Saline at 6
      Months: A Subgroup Analysis of a Multicenter, Randomized Controlled Trial.
AB  - Objective Many clinical trials of viscosupplementation have been conducted,
      although only the Gel-200 (primary) trial included a different patient
      population. A subgroup analysis of a multicenter, randomized controlled trial
      comparing the efficacy of single intra-articular injections of Gel-200 with
      phosphate buffered saline (PBS) was performed to demonstrate its benefit as
      treatment of osteoarthritis of the knee in a population similar to those of other
      reported trials of viscosupplementation. Design The subgroup population was
      defined as patients in the intention-to-treat (ITT) population who met the
      specified criteria. Changes from baseline in Western Ontario and McMaster
      Universities Arthritis Index (WOMAC) scores following treatment with Gel-200 or
      PBS were derived from a longitudinal model and treatment differences compared
      between groups at weeks 12 and 26, and over 26 weeks. Results The subgroup
      included 311 subjects (152 Gel-200; 159 PBS). Mean improvements from baseline in
      WOMAC pain subscores in the Gel-200 over PBS groups were statistically
      significant at week 12 ( P = 0.031) and week 26 ( P = 0.019). Treatment group
      differences in WOMAC stiffness and total scores were statistically significant at
      week 26 ( P = 0.023 and P = 0.036, respectively). Conclusions The efficacy of Gel
      200 following a single injection for knee osteoarthritis was demonstrated in
      WOMAC pain, stiffness, and total scores as well as clinically important
      improvements in pain at 26 weeks in this subset of patients with comparable
      characteristics to populations evaluated in other viscosupplementation treatment
      trials.

PMID- 29644877
TI  - Protective effects of folic acid on DNA damage and DNA methylation levels induced
      by N-methyl- N'-nitro- N-nitrosoguanidine in Kazakh esophageal epithelial cells.
AB  - The protective effects of folic acid on DNA damage and DNA methylation induced by
      N-methyl- N'-nitro- N-nitrosoguanidine (MNNG) in Kazakh esophageal epithelial
      cells were investigated using a 3 * 3 factorial design trial. The cells were
      cultured in vitro and exposed to media containing different concentrations of
      folic acid and MNNG, after which growth indices were detected. DNA damage levels
      were measured using comet assays, and genome-wide DNA methylation levels (MLs)
      were measured using high-performance liquid chromatography. The DNA methylation
      of methylenetetrahydrofolate reductase (MTHFR) and folate receptor- alpha (FR
      alpha) genes was detected by bisulfite sequencing polymerase chain reaction
      (PCR). The results showed significant increases in tail DNA concentration, tail
      length, and Olive tail moment ( p < 0.01); a significant reduction of genome-wide
      DNA MLs ( p < 0.01); and an increase in the methylation frequencies of MTHFR and
      FR alpha genes. In particular, significant differences were observed in the
      promoter regions of both genes ( p < 0.01). Our study indicated that a reduction
      in folic acid concentration promotes DNA damage and DNA methylation in Kazakh
      esophageal epithelial cells upon MNNG exposure. Thus, sufficient folic acid
      levels could play a protective role against the damage induced by this compound.

PMID- 29644876
TI  - The Effects of Well-Rounded Exercise Program on Systemic Biomarkers Related to
      Cartilage Metabolism.
AB  - Nonsurgical treatment such as exercise is the preferred method for management of
      knee osteoarthritis (OA). A combination of aerobic, muscle strengthening, and
      flexibility exercises is recommended for older adults. However, effects of the
      exercise intervention on cartilage metabolism remain unclear. This study used
      biomarkers to investigate the effects of well-rounded exercise program on
      cartilage metabolism in 42 women (mean age: 59 years). Participants started a
      weekly supervised exercise program and continued for 12 weeks. Before and after
      the program, we measured physical performance on the Timed Up-and-Go Test, 3
      Minute Walk Test, and 30-Second Chair Stand Test. We collected serum and urine
      samples at the start of the program until 24 weeks and measured the
      concentrations of 4 biomarkers related to type II collagen metabolism: serum
      cartilage type II procollagen carboxy propeptide (sPIICP), urine C-terminal
      telopeptide of collagen type II (uCTX-II), urine cleavage of type II collagen by
      collagenases (uC2C), and serum cartilage oligomeric matrix protein (sCOMP).
      Participants were divided into pre-OA and OA groups based on X-ray findings. The
      pre-OA group showed significant increases and decreases in sPIICP and uCTX-II
      concentrations with improved physical performance, respectively. sCOMP
      concentrations significantly increased in both groups. The exercise also improved
      physical performance with no detrimental effect on type II collagen metabolism in
      the OA group. Thus, well-rounded exercise may not only improve physical capacity
      but also have beneficial effects on type II collagen metabolism, especially in
      people without radiological OA.

PMID- 29644878
TI  - Investigation of the protective effects of crocin on acrylamide induced small and
      large intestine damage in rats.
AB  - We investigated repair of acrylamide (AA) induced damage in intestines by
      administration of crocin. We used 40 male Wistar rats in four groups of 10
      animals: control, AA, crocin, and AA + crocin groups. We investigated biochemical
      and histological changes to small and large intestine. AA ingestion decreased
      glutathione (GSH) levels and total antioxidant status (TAS) in the intestine
      compared to the control group, while superoxide dismutase (SOD) and catalase
      (CAT) activities, and total oxidant status (TOS) and malondialdehyde (MDA) levels
      were increased. Villi were shortened and villus degeneration was observed in
      ileum of the AA group. Degeneration of surface epithelium and Liberkuhn crypts
      were observed in colon sections. GSH and TAS levels increased after
      administration of AA together with crocin, while SOD and CAT levels and TOS and
      MDA levels decreased; significant recovery of histological damage also was
      observed. We found that crocin exhibits protective effects on AA induced small
      and large intestine damage by inhibiting oxidative stress.

PMID- 29644879
TI  - The executioner's shadow: Coerced sterilization and the creation of "Latin"
      eugenics in Chile.
AB  - Scholars such as Nancy Leys Stepan, Alexandra Minna Stern, Marius Turda and Aaron
      Gillette have all argued that the rejection of coerced sterilization was a
      defining feature of "Latin" eugenic theory and practice. These studies highlight
      the influence of neo-Lamarckism in this development not only in Latin America but
      also in parts of Europe in the first half of the twentieth century. This article
      builds upon this historiographical framework to examine an often-neglected site
      of Latin American eugenic knowledge production: Chile. By focusing on Chilean
      eugenicists' understandings of environment and coerced sterilization, this
      article argues that there was no uniquely Latin objection to the practice
      initially. In fact, Chilean eugenicists echoed concerns of eugenicists from a
      variety of locations, both "mainstream" and Latin, who felt that sterilization
      was not the most effective way to ensure the eugenic improvement of national
      populations. Instead, the article contends that it was not until the
      implementation of the 1933 German racial purity laws, which included coerced
      sterilization legislation, that Chilean eugenicists began to define their
      objections to the practice as explicitly Latin. Using a variety of medical texts
      which appeared in popular periodicals as well as professional journals, this
      article reveals the complexity of eugenic thought and practice in Chile in the
      early twentieth century.

PMID- 29644880
TI  - Effects of mirror therapy on walking ability, balance and lower limb motor
      recovery after stroke: a systematic review and meta-analysis of randomized
      controlled trials.
AB  - OBJECTIVE: To investigate the effects of mirror therapy on walking ability,
      balance and lower limb motor recovery in patients with stroke. METHOD: MEDLINE,
      EMBASE, Web of Science, CENTRAL, PEDro Database, CNKI, VIP, Wan Fang,
      ClinicalTrials.gov, Current controlled trials and Open Grey were searched for
      randomized controlled trials that investigated the effects of mirror therapy on
      lower limb function through January 2018. The primary outcomes included were
      walking speed, mobility and balance function. Secondary outcomes included lower
      limb motor recovery, spasticity and range of motion. Quality assessments were
      performed with the PEDro scale. RESULTS: A total of 13 studies ( n = 572) met the
      inclusion criteria. A meta-analysis demonstrated a significant effect of mirror
      therapy on walking speed (mean difference (MD) 0.1 m/s, 95% confidence interval
      (CI): 0.08 to 0.12, P < 0.00001), balance function (standard mean difference
      (SMD) 0.66, 95% CI: 0.43 to 0.88, P < 0.00001), lower limb motor recovery (SMD
      0.83, 95% CI: 0.62 to 1.05, P < 0.00001) and passive range of motion of ankle
      dorsiflexion (MD 2.07 degrees , 95% CI: 082 to 3.32, P = 0.001), without
      improving mobility (SMD 0.43, 95% CI: -0.12 to 0.98, P = 0.12) or spasticity of
      ankle muscles (MD -0.14, 95% CI: -0.43 to 0.15, P = 0.35). CONCLUSION: The
      systematic review demonstrates that the use of mirror therapy in addition to some
      form of rehabilitation appears promising for some areas of lower limb function,
      but there is not enough evidence yet to suggest when and how to approach this
      therapy.

PMID- 29644881
TI  - Comment on 'Lee Silverman Voice Treatment (LSVT)-BIG to improve motor function in
      people with Parkinson's disease: a systematic review and meta-analysis'.

PMID- 29644883
TI  - In vitro toxicity assessment of rivaroxaban degradation products and kinetic
      evaluation to decay process.
AB  - Degradation kinetics of oral anticoagulant rivaroxaban (RIV) was assessed in acid
      and alkaline media and while exposed to UVC radiation. Among all stress
      conditions tested, kinetic degradation process was better described by a zero
      order model. A stability indicating method was validated for the analysis of the
      anticoagulant RIV in tablets by high-performance liquid chromatography.
      Robustness was evaluated with a two-level Plackett-Burman experimental design.
      The effect of acute exposition of the human hepatoblastoma HepG2 cell line to RIV
      stressed samples (100 and 500 uM) was assessed through in vitro toxicity tests.
      MTT reduction, neutral red uptake, mitochondrial membrane potential, and low
      molecular weight DNA diffusion assays were employed for cytotoxicity evaluation
      (5*104 cells/well). The genotoxic potential was assessed by comet assay (2*104
      cells/well). Acute toxicity to HepG2 cells was assessed after 24 h incubation
      with sample solutions, for each test. A direct relationship between the increased
      amount of alkaline degradation products and higher cytotoxic potential was found.
      Results obtained by viability assay investigations support the concerns on risks
      associated with acute toxicity and genotoxicity of pharmaceutical samples
      containing degradation products as impurities.

PMID- 29644882
TI  - Estrogen-functionalized liposomes grafted with glutathione-responsive sheddable
      chotooligosaccharides for the therapy of osteosarcoma.
AB  - An estrogen (ES)-functionalized cationic liposomal system was developed and
      exploited for targeted delivery to osteosarcoma. Natural biocompatible
      chotooligosaccharides (COS, MW2-5 KDa) were covalently tethered to the liposomal
      surface through a disulfate bond (-SS-) to confer reduction-responsive COS
      detachment, whereas estrogen was grafted via polyethylene glycol (PEG 2 K) chain
      to achieve estrogen receptor-targeting. The liposomal carriers were prepared by
      the ethanol injection method and fluorescent anticancer drug doxorubicin (DOX)
      was loaded with ammonium sulfate gradient. The physicochemical properties,
      reduction-sensitivity, and the roles of estrogen on cellular uptake and tumor
      targeting were studied. The Chol-SS-COS/ES/DOX liposomes were spherical with an
      average size about 110 nm, and high encapsulation efficiency. The liposomes were
      stable in physiological condition but rapidly release the payload in response to
      tumoral intracellular glutathione (20 mM). MTT cytotoxicity assay confirmed that
      Chol-SS-COS/ES/DOX liposomes exhibited higher cytotoxicity to MG63 osteosarcoma
      cells than to liver cells (LO2). Flow cytometry (FCM) and confocal laser scanning
      microscopy revealed that cellular uptake of Chol-SS-COS/ES/DOX liposomes by MG63,
      than the free DOX or Chol-SS-COS/DOX. Ex vivo fluorescence distribution study
      showed that the multifunctional liposomes selectively accumulated in the MG63
      xenografts versus the organs. Chol-SS-COS/ES/DOX liposomes strongly inhibited the
      tumor growth and enhanced the animal survival rate. Overall, the COS grafted
      estrogen-functionalized cationic liposomes, fortified with glutathione
      responsiveness, showed great potential for specific intracellular drug delivery
      to estrogen receptor-expressing tumors such as osteosarcoma.

PMID- 29644884
TI  - Prospective Analysis of Surgical Bone Margins After Partial Foot Amputation in
      Diabetic Patients Admitted With Moderate to Severe Foot Infections.
AB  - BACKGROUND: Osteomyelitis is common in diabetic foot infections and medical
      management can lead to poor outcomes. Surgical management involves sending
      histopathologic and microbiologic specimens which guides future intervention. We
      examined the effect of obtainment of surgical margins in patients undergoing
      forefoot amputations to identify patient characteristics associated with
      outcomes. Secondary aims included evaluating interobserver reliability of
      histopathologic data at both the distal-to and proximal-to surgical bone margin.
      METHODS: Data were prospectively collected on 72 individuals and was pooled for
      analysis. Standardized method to retrieve intraoperative bone margins was
      established. A univariate analysis was performed. Negative outcomes, including
      major lower extremity amputation, wound dehiscence, reulceration, reamputation,
      or death were recorded. RESULTS: Viable proximal margins were obtained in 63 out
      of 72 cases (87.5%). Strong interobserver reliability of histopathology was
      recorded. Univariate analysis demonstrated preoperative platelets, albumin, probe
      to-bone testing, absolute toe pressures, smaller wound surface area were
      associated with obtaining viable margins. Residual osteomyelitis resulted in
      readmission 2.6 times more often and more postoperative complications.
      CONCLUSIONS: Certain patients were significantly different in the viable margin
      group versus dirty margin group. High interobserver reliability was demonstrated.
      Obtainment of viable margins resulted in reduced rates of readmission and
      negative outcomes. LEVELS OF EVIDENCE: Prognostic, Level I: Prospective.

PMID- 29644885
TI  - Short- to Mid-Term Outcomes Following the Use of an Arthroereisis Implant as an
      Adjunct for Correction of Flexible, Acquired Flatfoot Deformity in Adults.
AB  - BACKGROUND: The use of an arthroereisis implant for the treatment of adolescent
      flatfoot deformity has been described. However, data that address the outcomes of
      patients treated with an arthroereisis implant in adults are limited. The purpose
      of this study was to investigate the radiographic and clinical outcomes and
      complications following the use of a subtalar arthroereisis implant as an adjunct
      for correction acquired flatfoot deformity secondary to posterior tibial tendon
      dysfunction. METHODS: A retrospective case-control study was performed querying
      all patients undergoing surgical flatfoot correction between January 1, 2010 and
      January 1, 2015. The experimental group included patients undergoing
      arthroereisis augmentation at the time of flatfoot correction. Patients
      undergoing the same flatfoot correction without the use of an arthroereisis
      implant were used as controls. Radiographic measurements were evaluated
      preoperatively and at final radiographic follow-up and included talonavicular
      (TN) coverage angle, and lateral talar-first metatarsal angle (T1MA). Patient
      reported outcomes were assessed using preoperative visual analog scale (VAS) pain
      scores and postoperative Short Form-36, VAS, and satisfaction at final orthopedic
      follow-up. RESULTS: A total of 15 patients underwent flatfoot correction and were
      augmented with an arthroereisis implant and were matched with 30 controls.
      Postoperative, mid-term T1MA and regional analysis was found to be improved in
      the experimental group versus control. Patients undergoing adjunct subtalar
      arthroereisis demonstrated an increased likelihood of achieving radiographically
      normal talonavicular coverage <7 degrees  compared with our control group at
      follow-up. CONCLUSIONS: The adjunct use of an arthroereisis implant resulted in
      improved and maintained radiographic and clinical measurements in patients
      undergoing stage II flatfoot. CLINICAL SIGNIFICANCE: These results suggest
      utility of a subtalar arthroereisis implant as an adjunct to flatfoot correction
      with little additional risk of harm to the patient. LEVELS OF EVIDENCE: Level
      III: Case-control study.

PMID- 29644887
TI  - Post-traumatic stress reactions among individuals with visual impairments: a
      systematic review.
AB  - PURPOSE: To conduct a systematic review of post-traumatic stress reactions among
      individuals with visual impairment (VI). MATERIALS AND METHODS: Qualitative and
      quantitative studies were identified through searches in MEDLINE, EMBASE,
      PsycINFO, CINAHL, Web of Science, and Cochrane Libraries. The literature search
      was limited to humans, of English and Scandinavian languages and publication year
      between 1980 and 2017. Study quality was assessed for all the included studies
      and extracted data were synthesized using narrative analysis. RESULTS: Of 4235
      records identified through literature search, eleven were included in the
      analyses. Results from the qualitative studies illustrated multiple physical,
      behavioral, emotional, and cognitive manifestations of trauma. Four out of five
      quantitative studies showed that various types of potentially traumatic events
      were significantly associated with mental health adversities (p < 0.05). The
      prevalence of post-traumatic mental disorders was 4-21.2% for depression, 0.9%
      for dysthymia, and 32% for substance misuse. The quality of the reviewed studies
      was considered low to moderate. CONCLUSION: Traumatic experiences appear to have
      a great impact on the mental health in people with visual impairment (VI) and
      these results highlight their need for mental health care. Future studies with
      higher methodological rigor are recommended. Implications for rehabilitation
      Visual impairment entails a greater susceptibility to some types of potentially
      traumatic events, especially threats in everyday life. This calls for a greater
      emphasis on safe community environments and universal design in public spaces. In
      rehabilitation after serious accidents or potentially traumatic events,
      professionals working with people with vision impairment should be aware of the
      different manifestations of post-traumatic stress responses and that some stress
      responses may cause additional disability. The high prevalence of traumatic
      events and their impact on mental health in individuals with visual impairments
      highlights a need of mental health care.

PMID- 29644886
TI  - Effects of a Thermosensitive In Situ Gel Containing Mometasone Furoate on a Rat
      Allergic Rhinitis Model.
AB  - Background Mometasone furoate, one of the second generation intranasal
      corticosteroids, is currently used in suspension form due to its poor solubility.
      However, this is not favorable for nasal application because of the rapid
      elimination of the instilled drug from the nasal cavity by mucociliary clearance
      and delayed onset of action due to the slow dissolution of drug in suspension.
      Objective The aim of this study was to determine the antiallergic effects of
      mucoadhesive thermosensitive in situ gel containing mometasone furoate that we
      developed previously to prolong the contact between the drug and nasal mucosa and
      to prevent drainage of the formulation in an ovalbumin-induced rat model of
      allergic rhinitis. Methods An experimental allergic rhinitis model was developed
      in female Wistar albino rats by intraperitoneal injection of ovalbumin every 2
      days for 14 days followed by its repeated intranasal instillation for 7
      consecutive days. Intranasal instillation of ovalbumin was continued every other
      day for 14 days. Mometasone furoate in situ gel (5 MUg/10 ul), mometasone furoate
      suspension (5 MUg/10 ul), and physiological saline (10 ul) were administered into
      the bilateral nasal cavities from day 22 to day 35. Antiallergic effects were
      evaluated through histopathological evaluation, analysis of ovalbumin-specific
      serum immunoglobulin E, and a symptom score. Results Mometasone furoate in situ
      gel significantly decreased the nasal symptoms and ovalbumin-specific serum
      immunoglobulin E level as compared with mometasone furoate suspension and
      physiological saline. Additionally, inflammatory histological symptoms such as
      mucosal edema, vascular dilatation, eosinophil infiltration, and loss of cilia
      within the nasal mucosa of allergic rhinitis model rats were remarkably improved
      with the treatment of mometasone furoate in situ gel. Conclusion These results
      suggest that mometasone furoate in situ gel has a better therapeutic potential
      for the treatment of allergic rhinitis compared to mometasone furoate suspension.

PMID- 29644888
TI  - Motor skill training in musculoskeletal pain: a case report in chronic low back
      pain.
AB  - PURPOSE: Low back pain is a chronic condition that limits function. The chief
      reason individuals with low back pain seek care is difficulty performing
      functional activities. A novel approach to improving performance of painful and
      limited functional activities is motor skill training, defined as challenging
      practice of activities to learn or relearn a skill. The purpose of this report is
      to describe the design and application of a motor skill training intervention in
      a 26-year-old man with a 10-year history of low back pain. METHODS: A motor skill
      training intervention was implemented to modify the altered alignment and
      movement patterns he used during the performance of his painful and limited
      activities. RESULTS: The patient was seen for six visits in 12 weeks. The patient
      reported decreased pain and medication use, as well as improved function
      immediately, 3-, and 9-months post-intervention. CONCLUSION: Individuals with low
      back pain report limitation in ability to perform everyday functions and
      demonstrate altered patterns of movement and alignment during these activities.
      This case report describes an innovative motor skill training intervention that
      directly addresses the performance of functional activities and the application
      of motor learning principles. Implications for rehabilitation Low back pain is a
      chronic condition that limits function. The chief reason individuals with chronic
      low back pain seek care is difficulty performing everyday functional activities.
      Motor skill training is a novel approach that directly addresses the performance
      of painful and limited functional activities through challenging practice to
      improve performance and decrease pain.

PMID- 29644889
TI  - Comparing exercise responses to aerobic plus resistance training between
      postmenopausal breast cancer survivors undergoing aromatase inhibitor therapy and
      healthy women.
AB  - BACKGROUND: The aim of this study was to explore whether postmenopausal breast
      cancer survivors undergoing aromatase inhibitor therapy differ from healthy
      postmenopausal women in their response to the same aerobic + resistance training.
      METHODS: The participants were separated into two groups: postmenopausal breast
      cancer survivors undergoing aromatase inhibitor therapy for an average of 20
      months (18 women) and healthy postmenopausal women (24 women). We assessed
      aerobic capacity (predicted maximum oxygen uptake (VO2max) and maximum running
      velocity test (Vmax)) through a walking test, upper and lower body muscle
      strength using an estimated one-repetition maximum test, and body composition by
      dual-energy X-ray absorptiometry at baseline and at three, six, and nine months,
      respectively. The exercise program was performed three times/week over nine
      months and consisted of 40 min of machine-based strength training (seated cable
      row, bench press, leg extension, leg press, and leg curl, as well as bridge,
      abdominal, and standard plank exercises) followed by 30 min of treadmill walking.
      Analysis of variance (ANOVA) with repeated measures was used to compare the
      groups over time. RESULTS: Postmenopausal breast cancer survivors undergoing
      aromatase inhibitor therapy and healthy postmenopausal women presented similar
      improvements in estimated lower body strength, predicted VO2max and Vmax, and
      body fat mass. For maximal upper body strength, there was a significant group x
      time interaction after six months of training (p = 0.01). The healthy
      postmenopausal women presented a significant increase in upper body strength
      after six months, while postmenopausal breast cancer survivors undergoing
      aromatase inhibitor therapy demonstrated an improvement only at nine months of
      training. The breast cancer survivors undergoing aromatase inhibitor therapy
      presented increased lean mass while healthy postmenopausal women maintained
      values over time (Breast cancer: 33.7 +/- 3.9(Pre) vs. 34.1 +/- 3.4 kg (Post) and
      healthy women: 36.4 +/- 5.1 (Pre) vs. 36.4 +/- 5.0 kg (Post), p = 0.004).
      CONCLUSION: Our findings suggest that postmenopausal women undergoing aromatase
      inhibitor therapy for breast cancer demonstrated adaptations and similar
      trainability to the same regimen of resistance + aerobic training as healthy
      postmenopausal women. Implications for Rehabilitation Combined exercise program
      (aerobic plus resistance) is an important non-pharmacological strategies to
      improve strength, aerobic capacity, and body composition in breast cancer
      survivors undergoing aromatase inhibitor therapy. Furthermore, it is important to
      highlight that the time of intervention seems to influence the upper body
      strength response in this population. This study showed that trainers and other
      specialists do not need to modify the prescription of exercise related to healthy
      women, since the combined exercise program induced similar benefits in strength,
      aerobic capacity, and body composition in postmenopausal breast cancer survivors
      undergoing aromatase inhibitor therapy and healthy postmenopausal women.

PMID- 29644890
TI  - Adapting a Sexually Transmitted Infection Prevention Intervention Among Female
      Adolescents in Hawai'i.
AB  - Epidemiological data suggest that Native Hawaiian, Pacific Islander, and Asian
      American (NHPIA) adolescent females in Hawai'i are at elevated risk for sexually
      transmitted infections (STIs). These data also indicate that teen girls in
      Hawai'i are more likely to engage in high-risk sexual behaviors than boys.
      Despite this compelling evidence, there is a paucity of published research on
      effective STI prevention protocols that target NHPIA female adolescents. In light
      of this need, the purpose of this study was to adapt an evidence-based, group
      level STI behavioral prevention intervention targeting local NHPIA adolescent
      girls in Hawai'i for implementation by community-based organizations (CBOs). This
      article describes the adaptation of an evidence-based STI prevention intervention
      in partnership with a CBO, using a locally modified ADAPT-ITT model as a basis
      for the adaptation process. This research consisted of two phases: (1)
      development of an initial test version of an adapted intervention and (2) the
      development of the final version of the adapted intervention, Girl Power Hawai'i.
      The results provide the empirical and foundational research necessary for a
      tailored intervention that can be readily implemented by CBOs for local teen
      girls in Hawai'i.

PMID- 29644891
TI  - A survey of physiotherapists' current management and the promotion of physical
      activity, in people with rheumatoid arthritis.
AB  - PURPOSE: Establishing physiotherapists' management of people with rheumatoid
      arthritis, in addition to their promotion of physical activity, is important to
      ascertain if there are educational needs in this area. MATERIALS AND METHODS:
      Physiotherapists from three Irish Chartered Physiotherapy clinical interest
      groups (N = 457) were invited to participate in a cross-sectional online
      questionnaire hosted on SurveyMonkey(R)TM. RESULTS: One hundred and sixty-eight
      (168/457; 37%) responded. Exercise prescription and education were the most
      frequent treatments, with 84% always/regularly providing same. Physical activity
      is a component of treatment with 52% always/regularly advising. In addition, 69%
      agree that physical activity is attainable, 68% safe, and 67% an important goal.
      However, 62% never recommend the appropriate guidelines, while 14% define
      physical activity according to frequently used definitions. There was a
      statistically significant association between longer years qualified and more
      years working with people with RA, when using guidelines to guide physical
      activity and exercise prescription. Low-intensity exercises were prescribed by
      however, 67% never provide high-intensity. CONCLUSIONS: Current practice is in
      line with guidelines in which, exercise therapy and education are considered as
      the mainstay. Promotion of physical activity is strong; however, two-thirds never
      recommend the appropriate guidelines, and only a minority defined physical
      activity correctly. The majority never prescribe high-intensity exercise. There
      is a need to develop education and training for physiotherapists in the promotion
      of physical activity in people with rheumatoid arthritis. Implications for
      rehabilitation Exercise therapy and education are considered as the mainstay in
      the physiotherapy management of people with rheumatoid arthritis. Those
      physiotherapists' who are qualified longer and have more experience working with
      people with rheumatoid arthritis use the relevant physical activity guidelines.
      Overall there is a need to develop education and training for physiotherapists in
      the promotion of physical activity in people with rheumatoid arthritis.

PMID- 29644892
TI  - Recent developments in 3-D reconstruction and stereology to study the pulmonary
      vasculature.
AB  - Alterations of the pulmonary vasculature are an important feature of human lung
      diseases such as chronic obstructive pulmonary disease, pulmonary hypertension,
      and bronchopulmonary dysplasia. Experimental studies to investigate the
      pathogenesis or a therapeutic intervention in animal models of these diseases
      often require robust, meaningful, and efficient morphometric data that allow for
      appropriate statistical testing. The gold standard for obtaining such data is
      design-based stereology. However, certain morphological characteristics of the
      pulmonary vasculature make the implementation of stereological methods
      challenging. For example, the alveolar capillary network functions according to
      the sheet flow principle, thus making unbiased length estimations impossible and
      requiring other strategies to obtain mechanistic morphometric data. Another
      example is the location of pathological changes along the branches of the
      vascular tree. For developmental defects like in bronchopulmonary dysplasia or
      for pulmonary hypertension, it is important to know whether certain segments of
      the vascular tree are preferentially altered. This cannot be overcome by
      traditional stereological methods but requires the combination of a three
      dimensional data set and stereology. The present review aims at highlighting the
      great potential while discussing the major challenges (such as time consumption
      and data volume) of this combined approach. We hope to raise interest in the
      potential of this approach and thus stimulate solutions to overcome the existing
      challenges.

PMID- 29644893
TI  - Activation of the NF-kappaB pathway alters the phenotype of MSCs in the tracheal
      aspirates of preterm infants with severe BPD.
AB  - Mesenchymal stromal cells (MSCs) are released into the airways of preterm infants
      following lung injury. These cells display a proinflammatory phenotype and are
      associated with development of severe bronchopulmonary dysplasia (BPD). We aimed
      to characterize the functional properties of MSCs obtained from tracheal
      aspirates of 50 preterm infants who required invasive ventilation. Samples were
      separated by disease severity. The increased proliferative capacity of MSCs was
      associated with longer duration of mechanical ventilation and higher severity of
      BPD. Augmented growth depended on nuclear accumulation of NFkappaBp65 and was
      accompanied by reduced expression of cytosolic alpha-smooth muscle actin (alpha
      SMA). The central role of NF-kappaB signaling was confirmed by inhibition of
      IkappaBalpha phosphorylation. The combined score of proliferative capacity,
      accumulation of NFkappaBp65, and expression of alpha-SMA was used to predict the
      development of severe BPD with an area under the curve (AUC) of 0.847. We
      mimicked the clinical situation in vitro, and stimulated MSCs with IL-1beta and
      TNF-alpha. Both cytokines induced similar and persistent changes as was observed
      in MSCs obtained from preterm infants with severe BPD. RNA interference was
      employed to investigate the mechanistic link between NFkappaBp65 accumulation and
      alterations in phenotype. Our data indicate that determining the phenotype of
      resident pulmonary MSCs represents a promising biomarker-based approach. The
      persistent alterations in phenotype, observed in MSCs from preterm infants with
      severe BPD, were induced by the pulmonary inflammatory response. NFkappaBp65
      accumulation was identified as a central regulatory mechanism. Future preclinical
      and clinical studies, aimed to prevent BPD, should focus on phenotype changes in
      pulmonary MSCs.

PMID- 29644894
TI  - Decreased epithelial and sputum miR-221-3p associates with airway eosinophilic
      inflammation and CXCL17 expression in asthma.
AB  - Airway eosinophilic inflammation is a key feature of type 2 high asthma. The role
      of epithelial microRNA (miR) in airway eosinophilic inflammation remains unclear.
      We examined the expression of miR-221-3p in bronchial brushings, induced sputum,
      and plasma from 77 symptomatic, recently diagnosed, steroid-naive subjects with
      asthma and 36 healthy controls by quantitative PCR and analyzed the correlation
      between miR-221-3p expression and airway eosinophilia. We found that epithelial,
      sputum, and plasma miR-221-3p expression was significantly decreased in subjects
      with asthma. Epithelial miR-221-3p correlated with eosinophil in induced sputum
      and bronchial biopsies, fraction of exhaled nitric oxide, blood eosinophil,
      epithelial gene signature of type 2 status, and methacholine provocative dosage
      required to cause a 20% decline in forced expiratory volume in the first second
      in subjects with asthma. Sputum miR-221-3p also correlated with airway
      eosinophilia and was partially restored after inhaled corticosteroid treatment.
      Inhibition of miR-221-3p expression suppressed chemokine (C-C motif) ligand (CCL)
      24 (eotaxin-2), CCL26 (eotaxin-3), and periostin (POSTN) expression in BEAS-2B
      bronchial epithelial cells. We verified that chemokine (C-X-C motif) ligand
      (CXCL) 17, an anti-inflammatory chemokine, is a target of miR-221-3p, and
      epithelial CXCL17 expression significantly increased in asthma. CXCL17 inhibited
      CCL24, CCL26, and POSTN expression via the p38 MAPK pathway. Airway
      overexpression of miR-221-3p exacerbated airway eosinophilic inflammation,
      suppressed CXCL17 expression, and enhanced CCL24, CCL26, and POSTN expression in
      house dust mite-challenged mice. Taken together, epithelial and sputum miR-221-3p
      are novel biomarkers for airway eosinophilic inflammation in asthma. Decreased
      epithelial miR-221-3p may protect against airway eosinophilic inflammation by
      upregulating anti-inflammatory chemokine CXCL17.

PMID- 29644895
TI  - beta1-Subunit of the calcium-sensitive potassium channel modulates the pulmonary
      vascular smooth muscle cell response to hypoxia.
AB  - Accessory subunits associated with the calcium-sensitive potassium channel
      (BKCa), a major determinant of vascular tone, confer functional and anatomical
      diversity. The beta1 subunit increases Ca2+ and voltagesensitivity of the BKCa
      channel and is expressed exclusively in smooth muscle cells. Evidence supporting
      the physiological significance of the beta1 subunit includes the observations
      that murine models with deletion of the beta1 subunit are hypertensive and that
      humans with a gain-of-function beta1 mutation are at a decreased risk of
      diastolic hypertension. However, whether the beta1 subunit of the BKCa channel
      contributes to the low tone that characterizes the normal pulmonary circulation
      or modulates the pulmonary vascular response to hypoxia remains unknown. To
      determine the role of the BKCa channel beta1 subunit in the regulation of
      pulmonary vascular tone and the response to acute and chronic hypoxia, mice with
      deletion of the Kcnmb1 gene that encodes for the beta1 subunit ( Kcnmb1-/-) were
      placed in chronic hypoxia (10% O2) for 21-24 days. In normoxia, right ventricular
      systolic pressure (RVSP) did not differ between Kcnmb1+/+ (controls) and Kcnmb1-/
      mice. After exposure to either acute or chronic hypoxia, RVSP was higher in
      Kcnmb1-/- mice compared with Kcnmb1+/+ mice, without increased vascular
      remodeling. beta1 subunit expression was predominantly confined to pulmonary
      artery smooth muscle cells (PASMCs) from vessels <= 150 um. Peripheral PASMCs
      contracted collagen gels irrespective of beta1 expression. Focal adhesion
      expression and Rho kinase activity were greater in Kcnmb1-/- compared with
      Kcnmb1+/+ PASMCs. Compromised PASMC beta1 function may contribute to the
      heightened microvascular vasoconstriction that characterizes pulmonary
      hypertension.

PMID- 29644897
TI  - The feasibility, acceptability and preliminary efficacy of a low-cost, virtual
      reality based, upper-limb stroke rehabilitation device: a mixed methods study.
AB  - PURPOSE: To establish feasibility, acceptability, and preliminary efficacy of an
      adapted version of a commercially available, virtual-reality gaming system (the
      Personalised Stroke Therapy system) for upper-limb rehabilitation with community
      dwelling stroke-survivors. METHOD: Twelve stroke-survivors (nine females, mean
      age 58 years, [standard deviation 7.1], median stroke chronicity 42 months
      [interquartile range 34.7], Motricity index 14-25 for shoulder and elbow) were
      asked to complete nine, 40-min intervention sessions using two activities on the
      system over 3 weeks. Feasibility and acceptability were assessed through a semi
      structured interview, recording of adverse effects, adherence, enjoyment (using
      an 11-point Likert scale), and perceived exertion (using the BORG scale).
      Assessments of impairment (Fugl-Meyer Assessment Upper extremity), activity
      (ABILHAND, Action Research Arm Test, Motor Activity Log-28), and participation
      (Subjective Index of Physical and Social Outcome) were completed at baseline,
      following intervention, and at 4-week follow-up. Data were analysed using
      Thematic Analysis of interview and intervention field-notes and Wilcoxon Signed
      Ranks. Side-by-side displays were used to integrate findings. RESULTS:
      Participants received between 175 and 336 min of intervention. Thirteen non
      serious adverse effects were reported by five participants. Participants reported
      a high level of enjoyment (8.1 and 6.8 out of 10) and rated exertion between 11.6
      and 12.9 out of 20. Themes of improvements in impairments and increased
      spontaneous use in functional activities were identified and supported by
      improvements in all outcome measures between baseline and post-intervention (p <
      0.05 for all measures). CONCLUSIONS: Integrated findings suggested that the
      system is feasible and acceptable for use with a group of community-dwelling
      stroke-survivors including those with moderately-severe disability. Implications
      for rehabilitation To ensure feasibility of use and maintenance of an appropriate
      level of challenge, gaming technologies for use in upper-limb stroke
      rehabilitation should be personalised, dependent on individual need. Through the
      use of hands-free systems and personalisation, stroke survivors with moderate and
      moderately-severe levels of upper-limb impairment following stroke are able to
      use gaming technologies as a means of delivering upper-limb rehabilitation.
      Future studies should address issues of acceptability, feasibility, and efficacy
      of personalised gaming technologies for delivery of upper-limb stroke
      rehabilitation in the home environment. Findings from this study can be used to
      develop future games and activities suitable for use in stroke rehabilitation.

PMID- 29644896
TI  - PAI-1 is a novel component of the miR-17~92 signaling that regulates pulmonary
      artery smooth muscle cell phenotypes.
AB  - We have previously reported that miR-17~92 is critically involved in the
      pathogenesis of pulmonary hypertension (PH). We also identified two novel mR
      17/20a direct targets, PDZ and LIM domain protein 5 (PDLIM5) and prolyl
      hydroxylase 2 (PHD2), and elucidated the signaling pathways by which PDLIM5 and
      PHD2 regulate functions of pulmonary artery smooth muscle cells (PASMCs). In
      addition, we have shown that plasminogen activator inhibitor-1 (PAI-1) is also
      downregulated in PASMCs that overexpress miR-17~92. However, it is unclear
      whether PAI-1 is a direct target of miR-17~92 and whether it plays a role in
      regulating the PASMC phenotype. In this study, we have identified PAI-1 as a
      novel target of miR-19a/b, two members of the miR-17~92 cluster. We found that
      the 3'-untranslated region (UTR) of PAI-1 contains a miR-19a/b binding site and
      that miR-19a/b can target this site to suppress PAI-1 protein expression. MiR
      17/20a, two other members of miR-17~92, may also indirectly suppress PAI-1
      expression through PDLIM5. PAI-1 is a negative regulator of miR-17~92-mediated
      PASMC proliferation. Silencing of PAI-1 induces Smad2/calponin signaling in
      PASMCs, suggesting that PAI-1 is a negative regulator of the PASMC contractile
      phenotype. We also found that PAI-1 is essential for the metabolic gene
      expression in PASMCs. Furthermore, although there is no significant change in PAI
      1 levels in PASMCs isolated from idiopathic pulmonary arterial hypertension and
      associated pulmonary arterial hypertension patients, PAI-1 is downregulated in
      hypoxia/Sugen-induced hypertensive rat lungs. These results suggest that miR
      17~92 regulates the PASMC contractile phenotype and proliferation coordinately
      and synergistically by direct and indirect targeting of PAI-1.

PMID- 29644898
TI  - A New Chapter for the American Journal of Rhinology and Allergy.

PMID- 29644899
TI  - Technical notes on the endoscopic endonasal approach to the craniovertebral
      junction for odontoidectomy.
AB  - INTRODUCTION: Odontoidectomy can help decompress ventral compression of the
      brainstem and upper cervical spinal cord in the presence of bony abnormalities of
      the craniovertebral junction (CVJ), e.g., an odontoid pannus. Endonasal
      approaches have been shown to be associated with lower morbidity compared with
      traditional transoral approaches. We demonstrated an entirely endonasal approach
      to the CVJ. MATERIALS AND METHODS: We presented our technique for performing an
      endoscopic endonasal odontoidectomy. RESULTS: The patient underwent an open
      posterior cervical spinal fusion to stabilize the CVJ due to destabilization that
      occurs with odontoidectomy either as part of a single procedure or in a staged
      manner, depending on the surgeon's preference. By using a two-surgeon,
      multihanded technique in collaboration with neurosurgery, the anterior CVJ was
      safely approached endoscopically through the nasopharynx. A midline incision was
      created and the soft tissue was lateralized widely. The first cervical vertebra
      (C1) arch was removed with a drill exposing the odontoid process and any
      associated pannus, which were then resected. Because this approach was entirely
      extradural, no reconstruction was necessary. Closure was accomplished by placing
      absorbable packing material in the defect and medializing the nasopharyngeal
      tissues. CONCLUSION: Endoscopic endonasal odontoidectomy offers excellent
      exposure and less morbidity than traditional transoral approaches. This technique
      should be considered in appropriately selected patients.

PMID- 29644900
TI  - Discordance in Preoperative and Postoperative Histopathology of Sinonasal Tumors.
AB  - Background Head and neck surgical pathology has been shown to be prone to
      histopathologic diagnostic error that can adversely impact patient care due to
      inappropriate management. Sinonasal tumors, in particular, present a diagnostic
      challenge given the relative rarity and diversity in histology and thus may have
      higher rates of discordant histology. Objective The purpose of this study is to
      determine the rate of discrepancy between preoperative and postoperative
      diagnoses of sinonasal tumors. Methods Retrospective chart review was performed
      on 52 patients treated for sinonasal tumors between January 2013 and December
      2016. Initial diagnosis on preoperative biopsy was compared to postoperative
      diagnosis rendered at a single tertiary care referral center. A discrepant
      diagnosis was regarded as any change in diagnosis that resulted in further
      refinement of therapy or prognosis. Results Eleven (21.2%) patients had
      discrepancy between the preliminary pathology and postsurgical diagnosis. Of
      these diagnoses, four involved a change from a benign to a more aggressive benign
      or malignant process, three involved reclassification of a malignant tumor to a
      more aggressive histology, and four involved change from an aggressive process to
      benign histology. In all 11 cases, alteration in management strategy was
      rendered. The majority of discordant diagnoses were of fibro-osseous lesions and
      small round blue cell tumors. Conclusion Sinonasal tumors exhibit a high degree
      of discordance from preoperative to postoperative diagnosis. Critical decision
      making should be reserved until careful review of operative specimens is
      performed to minimize patient morbidity and unnecessary interventions.

PMID- 29644901
TI  - Eccentric, mature osseous cap: A distinct imaging feature of sinonasal
      osteoblastoma.
AB  - BACKGROUND: With the exception of osteomas, bone neoplasms that originate in the
      sinonasal cavity are seldom diagnosed on preoperative imaging due to a lack of
      characteristic radiographic features. Here we described the unusual occurrence of
      an osteoblastoma in the paranasal sinuses, and we drew focus to its salient
      imaging features. A highly unique imaging sign was indicated, and its pathologic
      basis was explained, with concurrent review of the literature. METHODS: Case
      series and review of the literature. RESULTS: Two cases of sinonasal
      osteoblastoma were managed by definitive surgical resection. Both tumors on
      preoperative computed tomography demonstrated an expansile, heterogeneous fibro
      osseous lesion with an eccentric, mature osseous cap. The dense osseous cap seen
      on imaging corresponded to a rim of mature bone on histopathology. A review of
      existing literature revealed the presence of this imaging sign in all reported
      cases. CONCLUSION: Sinonasal osteoblastoma is an extremely rare entity with
      undefined imaging characteristics to guide preoperative decision-making. Here we
      reported, to our knowledge, the first description of a characteristic imaging
      sign of an eccentric, mature osseous cap, which corresponded histologically to a
      single peripheral layer rim of osteoblasts, a unique trait of osteoblastoma.

PMID- 29644902
TI  - Interleukin (IL) 36 gamma induces mucin 5AC, oligomeric mucus/gel-forming
      expression via IL-36 receptor-extracellular signal regulated kinase 1 and 2, and
      p38-nuclear factor kappa-light-chain-enhancer of activated B cells in human
      airway epithelial cells.
AB  - BACKGROUND: Mucin 5AC, oligomeric mucus/gel-forming (MUC5AC) expression is
      significantly increased in allergic and inflammatory airway diseases. Interleukin
      (IL) 36 gamma is predominantly expressed in airway epithelial cells and plays an
      important role in innate and adaptive immune responses. IL-36 gamma is induced by
      many inflammatory mediators, including cytokines and bacterial and viral
      infections. However, the association between IL-36 gamma and mucin secretion in
      human airway epithelial cells has not yet been fully investigated. OBJECTIVE: The
      objective of this study was to determine whether IL-36 gamma might play a role in
      the regulation of mucin secretion in airway epithelial cells. We investigated the
      effect and brief signaling pathway of IL-36 gamma on MUC5AC expression in human
      airway epithelial cells. METHODS: Enzyme immunoassay, immunoblot analysis,
      immunofluorescence staining, reverse transcriptase-polymerase chain reaction
      (PCR), and real-time PCR were performed in mucin-producing human airway
      epithelial NCI-H292 cells and in human nasal epithelial cells after pretreatment
      with IL-36 gamma, several specific inhibitors, or small interfering RNAs (siRNA).
      RESULTS: IL-36 gamma induced MUC5AC expression and activated the phosphorylation
      of extracellular signal regulated kinase (ERK) 1 and 2, p38, and nuclear factor
      kappa-light-chain-enhancer of activated B cells (NF-kappa B). IL-36 receptor
      antagonist significantly attenuated these effects. The specific inhibitor and
      siRNA of ERK1, ERK2, p38, and NF-kappa B significantly attenuated IL-36 gamma
      induced MUC5AC expression. CONCLUSION: These results indicated that IL-36 gamma
      induced MUC5AC expression via the IL-36 receptor-mediated ERK1/2 and p38/NF-kappa
      B pathway in human airway epithelial cells.

PMID- 29644903
TI  - Patients with chronic rhinosinusitis and obstructive sleep apnea have increased
      paroxysmal limb movement.
AB  - BACKGROUND: Patients with chronic rhinosinusitis (CRS) frequently experience
      sleep disruption and are at a higher than normal risk for obstructive sleep apnea
      (OSA). The purpose of this study was to determine how CRS affects polysomnography
      findings and sleep-related breathing in OSA. METHODS: A cohort study was
      performed that included 107 adult patients with CRS and comorbid OSA (CRS+OSA
      group) and 137 patients with OSA and without CRS as the control group. An
      electronic medical records database was used to identify eligible subjects.
      Comorbid conditions and polysomnography data were compared between the two groups
      by using logistic and linear regression analyses. RESULTS: A total of 246
      patients were included: 107 patients in the CRS+OSA group and 137 patients with
      OSA and without CRS in the control group. After adjusting for demographic
      factors, the patients in the CRS+OSA group had a lower body mass index (BMI) and
      higher age at the time of diagnosis of OSA (p < 0.001). The patients in the
      CRS+OSA group had higher odds of having asthma and eczema. There was an increase
      in the periodic limb movement (PLM) index in the CRS+OSA group. Apnea and
      hypopnea indices were similar in the two groups. CONCLUSION: Patients with CRS
      developed OSA at a lower BMI; patients CRS and OSA had similar sleep-related
      breathing patterns but higher risks for PLMs compared with patients with OSA and
      without CRS.

PMID- 29644904
TI  - Survivin and cortactin expression in sinonasal schneiderian (inverted) papilloma
      and associated carcinoma.
AB  - BACKGROUND: Sinonasal inverted (schneiderian) papilloma (IP) is histologically
      benign but shows a propensity for malignant transformation. Survivin, a member of
      the inhibitor of the apoptosis family of proteins that controls cell division,
      apoptosis, metastasis, and, probably, also neoangiogenesis, is overexpressed in
      essentially all human cancers. Overexpression of the multidomain protein
      cortactin has also been associated with increased cell migration, invasion, and
      metastatic potential in several malignancies. OBJECTIVE: The aim of the present
      study was to preliminarily investigate survivin and cortactin expression in a
      consecutive series of sinonasal IPs, and IP-associated squamous cell carcinomas
      (SCC). METHODS: Immunohistochemical expression of nuclear survivin and cortactin
      was measured in 19 consecutive sinonasal IPs and 3 IP-associated SCCs. RESULTS:
      The mean +/- standard deviation nuclear survivin expression was 9.4 +/- 9.2% and
      31.7% +/- 15.4% in sinonasal IPs and SCCs, respectively (p < 0.0001). Results of
      cortactin immunostaining was strongly positive in the cytoplasm of both sinonasal
      IPs and SCCs: no significant difference emerged between the IP and SCC epithelial
      components. CONCLUSION: Nuclear survivin expression was significantly higher in
      SCCs than in IPs. Prospective, multi-institutional prognostic studies, preferably
      on an international scale (given the few cases treated at single institutions),
      are needed to confirm the role of survivin in IP malignant transformation.

PMID- 29644905
TI  - Histopathology in Chronic Rhinosinusitis Varies With Sinus Culture.
AB  - Background Structured histopathology reporting facilitates better understanding
      of the underlying pathophysiologic mechanisms of chronic rhinosinusitis. The
      microbiology of chronic rhinosinusitis has been studied extensively; however,
      distinct histopathologic changes associated with bacteria isolated in chronic
      rhinosinusitis are largely unknown. Objective The goal of this study is to better
      understand the relationship between culturable bacteria and histopathology in
      chronic rhinosinusitis. Methods A structured histopathology report was utilized
      to analyze sinus tissue removed during functional endoscopic sinus surgery in a
      group of patients with chronic rhinosinusitis refractory to medical therapy.
      Patients with cystic fibrosis or ciliary dysfunction were excluded. Histology
      variables included eosinophil count per high-power field, neutrophil infiltrate,
      basement membrane thickening, subepithelial edema, hyperplastic/papillary
      changes, mucosal ulceration, squamous metaplasia, fibrosis, fungal elements,
      Charcot-Leyden crystals, and eosinophil aggregates. Baseline Lund-Mackay score
      and Sinonasal Outcome Test 22 score were also collected. The association of
      culture data with the aforementioned variables was assessed. Results A total of
      59 chronic rhinosinusitis patients who underwent functional endoscopic sinus
      surgery were included. Chronic rhinosinusitis patients with Pseudomonas
      aeruginosa had significantly increased neutrophil infiltrate (71.4% vs. 26.9%, p
      = 0.048), subepithelial edema (28.6% vs. 3.8%, p = 0.047), and a trend toward
      increased fungal elements (28.6% vs. 5.8%, p = 0.071). Chronic rhinosinusitis
      patients with Staphylococcus aureus had significantly more hyperplastic changes
      (20% vs. 2.3%, p = 0.050) and a trend toward increased squamous metaplasia (33.3%
      vs. 14.2%, p = 0.069). Conclusion Distinct histopathologic changes were noted
      based on sinus culture data for S. aureus and P. aeruginosa. These findings may
      have important implications on the extent of surgical management and prognosis
      after surgery.

PMID- 29644906
TI  - Does Heating up Saline for Nasal Irrigation Improve Mucociliary Function in
      Chronic Rhinosinusitis?
AB  - Background Mucociliary function is affected by temperature. Exposure to cold air
      may impair ciliary beat frequency. While saline nasal irrigation improves in
      ciliary beat activity, there is no evidence supporting the use of heated saline
      irrigation in treating patients with chronic rhinosinusitis. Objective To compare
      the effects of heated saline to room-temperature saline nasal irrigation on
      mucociliary clearance in chronic rhinosinusitis patients. Methods Adult patients
      with chronic rhinosinusitis were randomized into two groups receiving either
      heated saline or room-temperature saline nasal irrigation. Healthy subjects were
      included as control. Saccharin transit time was measured before and after nasal
      irrigation. Nasal patency was assessed by peak nasal inspiratory flow, anterior
      rhinomanometry, acoustic rhinometry, nasal obstruction score, and breathe-comfort
      score. Any adverse events were reported. Results Twenty-three patients with
      chronic rhinosinusitis and nine healthy subjects were enrolled. Saccharin transit
      time was decreased after nasal irrigation in both heated saline subgroup
      (baseline 12.3 +/- 4.5 min vs. postirrigation 8.4 +/- 4.9 min, p = 0.05) and room
      temperature subgroup (baseline 12.8 +/- 5.0 min vs. postirrigation 8.9 +/- 4.2
      min, p = 0.01). The saccharin transit time improvement was not different between
      heated saline (3.8 +/- 6.2 min) and room-temperature saline (3.8 +/- 4.0 min), p
      = 0.13. Postheated saline irrigation saccharin transit time of chronic
      rhinosinusitis patients (8.4 +/- 4.9 min) was not different to healthy subjects
      (9.2 +/- 3.7 min), p = 0.69. Nasal patency was not different between groups.
      There was no adverse event reported. Conclusion Nasal saline irrigation is
      beneficial to patients with chronic rhinosinusitis on mucociliary improvement.
      Warming saline is not necessary and adds no additional benefit to room
      temperature saline irrigation.

PMID- 29644907
TI  - Remodeling of the Paradoxical Middle Turbinate: Preserving Function While Gaining
      Access.
AB  - Background Endoscopic sinus surgery is performed for many reasons, most commonly
      for chronic rhinosinusitis refractory to medical treatment. A paradoxical middle
      turbinate is an anatomic variant that can hinder endoscopic access to the
      sinuses. No publication has addressed how to surgically treat a paradoxical
      middle turbinate. Method We present a basic endoscopic surgical approach to
      conservatively resect a paradoxical middle turbinate in order to improve access
      to the middle meatus and the sinuses while preserving support and function.
      Conclusion Conservative remodeling of the paradoxical middle turbinate can
      provide access to the sinuses while maintaining a significant portion of the
      middle turbinate.

PMID- 29644908
TI  - Life Course Stage and Social Support Mobilization for End-of-Life Caregivers.
AB  - Caregivers of terminally ill patients are at risk for anxiety, depression, and
      social isolation. Social support from friends, family members, neighbors, and
      health care professionals can potentially prevent or mitigate caregiver strain.
      While previous research documents the importance of social support in helping end
      of-life caregivers cope with caregiving demands, little is known about
      differences in social support experiences among caregivers at different life
      course stages. Using life course theory, this study analyzes data from in-depth
      interviews with 50 caregivers of patients enrolled in hospice services to compare
      barriers to mobilizing social support among caregivers at two life course stages:
      midlife caregivers caring for parents and older adult caregivers caring for
      spouses/partners. Older adult caregivers reported different barriers to
      mobilizing social support compared with midlife caregivers. Findings enhance the
      understanding of how caregivers' life course stage affects their barriers to
      mobilization of social support resources.

PMID- 29644909
TI  - Advanced ERCP techniques for the extraction of complex biliary stones: a single
      referral center's 12-year experience.
AB  - OBJECTIVES: Advanced ERCP techniques (AETs) for difficult biliary stones include
      peroral cholangioscopy (POC) with electrohydraulic/laser lithotripsy (EHL/LL),
      endoscopic papillary large balloon dilation (EPLBD) and mechanical lithotripsy
      (ML). We assess the efficacy of AETs. METHODS: A retrospective query for AETs.
      PRIMARY OUTCOME: Complete duct clearance. Secondary outcome: Complete duct
      clearance by technique. Statistical Analysis version 9.3 (SAS Inc., Cary, NC).
      RESULTS: From 1/00 to 10/12, 349 patients were identified of which 222 (80% had
      prior ERCPs) had AETs. 211 with sufficient follow-up underwent 295 ERCPs; 280 of
      which were AET's. Index AETs: POC with EHL/LL (n = 46/211, 22%), ML (n = 84/211,
      40%), EPLBD with mean balloon size of 11.5 +/- 1.7 mm (n = 39/211, 18%) and
      combination AETs (n = 42/211, 20%). Stone characteristics: 76% had >=1 stone, 81%
      extrahepatic and 32% had strictures. Number of stones (mean 2.5 and range 1-20)
      did not differ among groups. EPLBD had higher percentage (95%) of extrahepatic
      stones (p = .0003). The 'Combination' and 'POC' groups had larger stones (mean
      17.7 mm +/-6.4 and 16.8 mm +/-6.1, respectively; p < .001). Complete clearance:
      209/211 (99%) at index AET 167/211 (79%) or after mean of 2.5 +/- 0.7 AETs in
      42/211 (20%). Partial clearance: 2/211 (1%). Clearance at index AETs was higher
      with EPLBD (90%, p = .014). Adverse Events: 7/280 (2.5%). CONCLUSIONS: AETs
      achieved clearance in 99%. EPLBD had higher clearance at index AET likely owing
      to higher extrahepatic stones. Larger stones, but not number, were associated
      with increased combination AETs and total ERCPs.

PMID- 29644910
TI  - Encapsulation of biological active phenolic compounds extracted from wine wastes
      in alginate-chitosan microbeads.
AB  - Grapes (Vitis vinifera) are produced in large amounts worldwide and mostly are
      used for winemaking. Their untreated wastes are rich in valuable secondary
      metabolites, such as phenolics. Thus, in this study, white and red wine wastes
      (Malagouzia and Syrah variety) were investigated for their added value phenolics,
      which were analysed by high performance liquid chromatography (HPLC) and
      electrospray ionisation-mass spectrometry (ESI/MS) and subsequently encapsulated
      in several polymers. Extracts from all wastes gave high amounts of total
      phenolics (13 +/- 2.72-22 +/- 2.69 mg g-1) and possessed high antioxidant
      activity (67-97%). In addition to their significant antibacterial activity
      against gram-negative and gram-positive bacteria, interesting results were also
      obtained from their anti-inflammatory and antiplatelet activity, in vitro.
      Encapsulation of the extracts was selective, leaving out most of sugars and other
      organic compounds when alginate-chitosan was used. Encapsulation efficiency
      recorded for all extracts ranged from 55% to 79%. Release studies were also
      performed in several solutions aiming in their commercial use in food and
      pharmaceutical industries.

PMID- 29644911
TI  - Perceived doctor-patient relationship and satisfaction with general practitioner
      care in older persons in residential homes.
AB  - OBJECTIVE: Understanding patient satisfaction from the perspective of older
      adults is important to improve quality of their care. Since patient and care
      variables which can be influenced are of specific interest, this study examines
      the relation between patient satisfaction and the perceived doctor-patient
      relationship in older persons and their general practitioners (GPs). DESIGN:
      Cross-sectional survey. SUBJECTS AND SETTING: Older persons (n = 653, median age
      87 years; 69.4% female) living in 41 residential homes. MAIN OUTCOME MEASURES:
      Patient satisfaction (report mark) and perceived doctor-patient relationship
      (Leiden Perioperative care Patient Satisfaction questionnaire); relationships
      were examined by comparing medians and use of regression models. RESULTS: The
      median satisfaction score was 8 (interquartile range 7.5-9; range 0-10) and
      doctor-patient relationship 65 (interquartile range 63-65; range 13-65). Higher
      satisfaction scores were related to higher scores on doctor-patient relationship
      (Jonckheere Terpstra test, p for trend <.001) independent of gender, age,
      duration of stay in the residential home, functional and clinical
      characteristics. Adjusted for these characteristics, per additional point for
      doctor-patient relationship, satisfaction increased with 0.103 points (beta =
      0.103, 95% CI 0.092-0.114; p < .001). In those with a 'low' doctor-patient
      relationship rating, the percentage awarding 'sufficient or good' to their GP for
      'understanding about the personal situation' was 12%, 'receiving attention as an
      individual' 22%, treating the patient kindly 78%, and being polite 94%.
      CONCLUSION: In older persons, perceived doctor-patient relationship and patient
      satisfaction are related, irrespective of patient characteristics. GPs may
      improve patient satisfaction by focusing more on the affective aspects of the
      doctor-patient relationship. Key Points Examination of the perceived doctor
      patient relationship as a variable might better accommodate patients'
      expectations and improve satisfaction with the provided primary care.

PMID- 29644912
TI  - Amalgamation of systemic inflammatory response syndrome score with C-reactive
      protein level in evaluating acute pancreatitis severity in children.
AB  - BACKGROUND AND AIM: Systemic inflammatory response syndrome (SIRS) has to do with
      how the body reacts to injury. Herein, we analyzed the clinical features of acute
      pancreatitis (AP) in children with SIRS complication and investigated the role of
      SIRS score combined with C-reactive protein (CRP) level in assessing AP severity
      in children. METHODS: This retrospective cohort study involved 111 children
      hospitalized with AP at the Children's Hospital of Zhejiang University School of
      Medicine between January 2012 and August 2017. Presence of SIRS, demographic
      data, clinical information and laboratory test results on admission were
      statistically examined. RESULTS: Out of the 111 AP cases, 45 were diagnosed with
      SIRS. Differences in CRP, interleukin-6 (IL-6), age, temperature, heart rate
      (HR), white blood cell (WBC), neutrophil count (NC), body mass index (BMI),
      duration of onset of disease symptoms as well as cases requiring intensive care
      unit (ICU) treatment were significantly higher in patients with SIRS than those
      without SIRS (p < .01 or p < .05). Logistic regression analyses evinced two
      independent risk factors for SIRS to be coexisted diseases (odds ratio (OR) =
      4.871, p = .02) and fever (OR = 3.56, p = .007). SIRS was an independent
      predictor for AP severity (OR = 10.820, p = .005). The optimal cut-off value of
      CRP was 27.5 mg/L for severe AP classification according to receiver operating
      characteristic (ROC) (area under curve was 0.733). CONCLUSION: Amalgamation of
      SIRS criterion with CRP level potentially plays an important role in assessing AP
      severity in children.

PMID- 29644913
TI  - Possible modifier genes in the variation of neurofibromatosis type 1 clinical
      phenotypes.
AB  - Neurofibromatosis type 1 (NF1) is the most common neurogenetic disorder
      worldwide, caused by mutations in the (NF1) gene. Although NF1 is a single-gene
      disorder with autosomal-dominant inheritance, its clinical expression is highly
      variable and unpredictable. NF1 patients have the highest known mutation rate
      among all human disorders, with no clear genotype-phenotype correlations.
      Therefore, variations in NF1 mutations may not correlate with the variations in
      clinical phenotype. Indeed, for the same mutation, some NF1 patients may develop
      severe clinical symptoms whereas others will develop a mild phenotype. Variations
      in the mutant NF1 allele itself cannot account for all of the disease
      variability, indicating a contribution of modifier genes, environmental factors,
      or their combination. Considering the gene structure and the interaction of
      neurofibromin protein with cellular components, there are many possible candidate
      modifier genes. This review aims to provide an overview of the potential modifier
      genes contributing to NF1 clinical variability.

PMID- 29644915
TI  - Hyperphosphorylated Tau as a Novel Biomarker for Traumatic Axonal Injury in the
      Spinal Cord.
AB  - Current biomarker research in spinal cord injury (SCI) and traumatic brain injury
      has focused on a number of structural protein candidates, including the
      microtubule-associated protein tau. Evidence from models of traumatic brain
      injury has demonstrated that hyperphosphorylation of tau (p-tau) occurs in
      injured axons and demonstrates its utility as a biomarker for brain injury;
      however, the potential of p-tau as a biomarker for SCI is not yet known.
      Therefore, the present study determined whether tau is hyperphosphorylated in
      injured spinal cord axons, and then examined cerebrospinal fluid (CSF) and serum
      concentrations of p-tau and total-tau protein after a clinically relevant severe
      impact-compression SCI in rats. We found that severe SCI at T8 showed the
      presence of p-tau in damaged axons with a similar time course and distribution
      pattern to beta-APP, a biomarker of axonal injury. The presence of p-tau and beta
      APP positive axons extended no farther than 5000 MUm rostral and caudal to the
      injury epicenter, and was at its maximum at one day post-SCI. CSF levels of p-tau
      and total-tau significantly increased at one day post-SCI; however, only serum p
      tau levels were significantly elevated in rats with SCI compared with naive rats.
      These results suggest that CSF and serum p-tau may be a useful biomarker for
      severe traumatic SCI.

PMID- 29644914
TI  - On using wearable tri-axial accelerometers to examine the striking phase
      kinematics of expert specialist drag flickers on-field.
AB  - Analysing player kinematics during a match using "gold-standard" 3D video-based
      motion analysis techniques is a difficult prospect indeed. The development of
      small, wireless, wearable sensors offers the potential to reduce the challenges
      of measuring kinematics during match-play without hindering performance. The
      present study examined the viability of using wireless tri-axial accelerometers
      to examine whether key performance measures of drag flicks executed by expert
      specialist drag-flickers are predicted by the kinematics of the striking phase.
      Linear mixed models were used to examine whether the speed and accuracy of
      players' drag flicks were predicted by the duration of stick-ball contact, and
      the kinematics of the lead lower limb at stick-ball contact and ball release.
      Results revealed that stick and lead lower limb kinematics significantly
      predicted shot accuracy but not shot speed. Shorter drag-time predicted more
      accurate flicks (p = 0.03) as did a more vertical leg at stick-ball contact (p =
      0.016) and a more horizontal thigh at ball release (p = 0.001). This may indicate
      that there are more ways to produce fast drag flicks than accurate ones. This
      study illustrates that wireless tri-axial accelerometers can be used on-field to
      measure the effects of kinematics on key performance measures.

PMID- 29644916
TI  - Predicting the toxicities of metal oxide nanoparticles based on support vector
      regression with a residual bootstrapping method.
AB  - For safely using the untested metal oxide nanoparticles (MONPs) in industrial and
      commercial applications, it is important to predict their potential toxicities
      quickly and efficiently. In this research, the quantitative structure-activity
      relationship (QSAR) model based on support vector regression (SVR) with a
      residual bootstrapping technique (BTSVR) was proposed to predict the toxicities
      of MONPs. It was found that the main features influencing the toxicities of MONPs
      were RAatom (atomic ratio of oxygen to metal), DeltaHm (enthalpy of melting), and
      Ecoh (cohesive energy). The QSPR model constructed was robust and self
      explanatory in predicting the toxicities of MONPs with the coefficient of
      determination (R2) of 0.87 and the root mean square error (RMSE) of 0.184 for the
      training sets, and R2 of 0.84 and RMSE of 0.217 for the testing sets,
      respectively. The performance of our model is much better than that published.
      Moreover, our model was validated by the external testing sets 1000 times.
      Therefore, it is expected that the method presented here can be used to construct
      powerful model in predicting the toxicities of MONPs untested or even
      unavailable.

PMID- 29644917
TI  - Manipulations of distractor frequency do not mitigate emotion-induced blindness.
AB  - Emotional distractors can impair perception of subsequently presented targets, a
      phenomenon called emotion-induced blindness. Do emotional distractors lose their
      power to disrupt perception when appearing with increased frequency, perhaps due
      to desensitisation or enhanced recruitment of proactive control? Non-emotional
      tasks, such as the Stroop, have revealed that high frequency distractors or
      conflict lead to reduced interference, and distractor frequency appears to
      modulate attentional capture by emotional distractors in spatial attention tasks.
      But emotion-induced blindness is thought to reflect perceptual competition
      between targets and emotional distractors, and it is unclear whether high
      frequency emotional stimuli cause less disruption at this relatively early stage
      of processing. In four experiments, participants searched streams of images for a
      rotated target image. A negative or neutral distractor appeared before the
      target, and their relative frequency was manipulated. Across all experiments, the
      frequency of emotional distractors did not modulate emotion-induced blindness
      even when participants were explicitly informed that they would appear often or
      seldom. Thus, increased distractor frequency does not appear to mitigate the
      priority allotted to emotional distractors during perceptual competition.

PMID- 29644918
TI  - Assessment of clinical sepsis-associated biomarkers in a septic mouse model.
AB  - Objective Clinical sepsis-associated biomarkers were utilized in a cecal ligation
      and puncture (CLP) septic mouse model to provide a reference for investigating
      pathophysiological mechanisms and evaluating novel therapeutic interventions for
      sepsis. Methods Sepsis in mice was induced by CLP, and clinical biomarkers were
      evaluated (survival rate, blood physiological and biochemical indices, cytokines,
      hepatorenal function parameters, and blood coagulation). Results The mortality
      rate was >70%. The body temperature, blood pressure, and heart rate decreased
      within 48 h. Low lactic acid was found at 8 h. The CLP mice showed typical
      inflammatory symptoms with decreased white blood cells and procalcitonin and
      increased levels of soluble triggering receptor expressed on myeloid cells-1,
      interleukin (IL)-6, IL-10, tumor necrosis factor-alpha, macrophage inflammatory
      protein (MIP)-1alpha, MIP-1beta, and MIP-2. The platelet count and activated
      partial thromboplastin time significantly decreased, and the prothrombin time and
      prothrombin time-international normalized ratio markedly increased. Phenotypes of
      multiple organ dysfunction were found in the CLP model, including increased liver
      alanine aminotransferase and aspartate transaminase; significantly reduced total
      protein, globulin, and serum albumin; increased blood urea nitrogen and
      creatinine; and decreased blood glucose. Conclusion The clinical features of the
      CLP mouse model were similar to those of human patients with sepsis.

PMID- 29644919
TI  - High neutrophil-lymphocyte ratio in schizophrenia independent of infectious and
      metabolic parameters.
AB  - BACKGROUND: Immunological and inflammatory mechanisms play an important role in
      schizophrenia. In the literature, there are studies investigating neutrophil
      lymphocyte ratio (NLR) association with schizophrenia. AIMS: The purpose of this
      study was to compare NLR values between patients with schizophrenia and healthy
      controls. In addition, the study aimed to investigate the relationship between
      NLR and disease severity and some metabolic/inflammatory parameters. METHODS:
      Fifty-two patients diagnosed with schzophrenia and 53 healthy controls were
      included in the study. A socio-demographic information form was filled out by the
      clinician. Height, body weight, waist and hip circumference and blood pressure
      values of each patient were measured. Severity of disease was assessed by
      positive and negative syndrome scale (PANSS) and clinical global impression
      severity scale (CGI-S). Complete blood count was performed to both patient and
      control groups. Fasting blood glucose, insulin, HbA1c, low-density lipoprotein
      (LDL), high-density lipoprotein (HDL), triglyceride, total cholesterol and C
      reactive protein (CRP) were measured. RESULTS: The number of leukocytes,
      neutrophils, monocytes and NLR values in patients with schizophrenia was
      significantly higher than in the control group. There was no significant
      relationship between NLR values and the number of hospitalisation, duration of
      ilness or disease severity in patients. There was no correlation between other
      laboratory findings and NLR values. CONCLUSION: NLR levels are high in
      schizophrenia independent of metabolic parameters according to the results. So,
      it can be considered that inflammatory processes may play a role in the etiology
      of the disease.

PMID- 29644920
TI  - Sick-listed workers' expectations about and experiences with independent medical
      evaluation: a qualitative interview study from Norway.
AB  - PURPOSE: To reduce the country's sick leave rate, Norwegian politicians have
      suggested independent medical evaluations (IMEs) for sick-listed workers. IME was
      tested in a large, randomized controlled trial in one Norwegian county
      (Evaluation of IME in Norway, or 'the NIME trial'). The current study's aim was
      to explore sick-listed workers' expectations about and experiences with
      participating in an IME. MATERIAL AND METHODS: Nine individual semi-structured
      telephone interviews were conducted. Our convenience sample included six women
      and three men, aged 35-59 years, who had diverse medical reasons for being on
      sick leave. Systematic text condensation was used for analysis. RESULTS: The
      participants questioned both the IME purpose and timing, but felt a moral
      obligation to participate. Inadequate information provided by their general
      practitioner (GP) to the IME doctor was considered burdensome by several
      participants. However, most participants appreciated the IME as a positive
      discussion, even if they did not feel it had any impact on their follow-up or
      return-to-work process. CONCLUSIONS: According to the sick-listed workers the
      IMEs were administered too late and disturbed already initiated treatment
      processes and return to work efforts. Still, the consultation with the IME doctor
      was rated as a positive encounter, contrary to their expectations. Our results
      diverge from findings in other countries where experiences with IME consultations
      have been reported as predominantly negative. These findings, along with
      additional, upcoming evaluations, will serve as a basis for the Norwegian
      government's decision about whether to implement IMEs on a regular basis. Key
      points   Independent medical evaluations for sick-listed workers has been tested
      out in a large Norwegian RCT and will be evaluated through qualitative interviews
      with participating stakeholders and by assessing the effects on RTW and
      costs/benefits. In this study, we explored sick-listed workers' expectations
      about and experiences with participating in an IME.   * Participants questioned
      both the IME purpose and timing, but felt a moral obligation to participate.   *
      Inadequate information provided by their general practitioner (GP) to the IME
      doctor was considered burdensome by several participants   * Sick-listed workers
      appreciated the IME as a positive discussion, even if they did not feel it had
      any impact on their follow-up or return-to-work process.

PMID- 29644921
TI  - Cognitive Frailty and Its Association with All-Cause Mortality among Community
      Dwelling Older Adults in Taiwan: Results from I-Lan Longitudinal Aging Study.
AB  - BACKGROUND: The definition of cognitive frailty and its prediction for adverse
      outcome of community-living older adults remains controversial. This study aims
      to evaluate the association between cognitive frailty and all-cause mortality
      among community-living older adults. METHODS: Data of the I-Lan Longitudinal
      Aging Study (ILAS) were retrieved for study. Frailty was defined by Fried's
      criteria, and a series of neuropsychological assessments, including the Mini
      Mental State Examination (MMSE), Center for Epidemiology Studies-Depression (CES
      D), the delay free recall in the Chinese Version Verbal Learning Test, the Boston
      Naming Test, the category (animal) Verbal Fluency Test, the Taylor Complex Figure
      Test, the digital backward and the Clock Drawing Test were performed. All
      participants received blood sampling after 10-h overnight fast for various
      biochemical markers. Cognitive frailty was defined as the concomitant presence of
      dynapenia and cognitive declines in any domains. RESULTS: Overall, data of 678
      participants aged 65 years and older (mean age: 73.3+/-5.3 years) were obtained
      for study. The prevalence of cognitive frailty in this study was 13.3%. People
      with cognitive frailty were significantly older, having higher multimorbidity
      burden, more likely to be women and had less skeletal muscle mass. Adjusted for
      age and gender, both dynapenia without cognitive impairment (HR: 5.402; 95% CI:
      1.463 - 19.954; P=0.011) and cognitive frailty (HR: 6.682; 95% CI: 1.803- 26.116;
      P=0.005) were significantly associated with all-cause mortality. CONCLUSIONS: The
      prevalence of cognitive frailty was 13.3% in Taiwan and was predictive for all
      cause mortality. Further study is needed to explore the pathophysiology and
      reversibility of cognitive frailty.

PMID- 29644923
TI  - Patients' characteristics and their influence on course of fear during
      agoraphobic symptom provocation: may SS(N)RI treatment compensate unfavorable
      individual preconditions?
AB  - BACKGROUND: Patients' characteristics and antidepressants are discussed to be
      relevant in the context of phobic exposure. AIMS: To identify patients
      characteristics associated with a differential course of fear during disorder
      specific symptom provocation as well as to elucidate the effect of selective
      serotonin-(noradrenalin-) reuptake inhibitors [SS(N)RI] on development of fear in
      the context of re-exposure to the phobic stimuli. METHODS: Twenty-eight
      clinically well-characterized patients with panic disorder and agoraphobia
      (PD/AG) were classified into subjects who show a reduction of fear ('Fear-')
      during a symptom provocation via a picture-based paradigm (T1) and those who did
      not ('Fear+'). Subsequently, SS(N)RI treatment was administered to all patients
      and subjects were re-exposed to the feared stimuli after 8 weeks of treatment
      (T2). Moreover, brain activity within the 'fear network' was measured via
      functional magnetic resonance imaging (fMRI) at T1 and T2. RESULTS: Fear - were
      significantly younger and demonstrated increased exposure-related fear as well as
      stronger activity in several fear-related brain areas than Fear+. We found
      significant improvements in all clinical parameters after pharmacological
      intervention for the whole sample (T1-T2; all measures p < .02). However,
      reduction of fear as well as activation in (para)limbic structures during symptom
      provocation were now attenuated in Fear - but increased in Fear+. CONCLUSIONS:
      Advanced age may predict a therapeutically unfavorable course of fear during
      agoraphobic symptom provocation. Since we found no negative impact of medication
      on fear development at all, there was some evidence that SS(N)RI treatment might
      improve the individual ability to get involved with the agoraphobic stimuli while
      conducting disorder-specific exposure.

PMID- 29644922
TI  - Chemerin rs17173608 and vaspin rs2236242 gene variants on the risk of end stage
      renal disease (ESRD) and correlation with plasma malondialdehyde (MDA) level.
AB  - INTRODUCTION: End-stage renal disease (ESRD) is associated with critical kidney
      illness that seriously affects the lifespan. Genetic factors and oxidative stress
      could play critical role in the development of ESRD. We assessed the association
      between chemerin rs17173608 T/G and vaspin rs2236242 T/A genes variants with the
      risk of ESRD and their correlation with plasma malondialdehyde (MDA) level.
      MATERIALS AND METHODS: In a case-control study, 131 gender and age-matched
      unrelated healthy controls and 110 ESRD patients were enrolled. The chemerin
      rs17173608 T/G and vaspin rs2236242 T/A were detected by Tetra primer
      amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR).
      The MDA concentration was determined by HPLC. RESULTS: Our findings for the first
      time revealed that in codominant genetic model (T/G vs. T/T genotype), the T/G
      genotype of chemerin gene significantly had a protective role against ESRD
      susceptibility. Also, in the presence of chemerin G allele, the risk of ESRD
      decreased by 0.79-fold (p = .048) in Kurdish population of Iran. The MDA serum
      levels in ESRD patients carrying the chemerin T/G + G/G genotype of rs17173608
      T/G and also in carriers of A/A + T/A genotype of vaspin rs2236242 T/A were
      significantly higher compared to those in control subjects. The overall
      distribution of vaspin rs2236242 T/A genotypes and alleles comparing ESRD
      patients and healthy subjects were not statistically significant. CONCLUSION: We
      found that the G allele of chemerin rs17173608 compared to T allele decreased the
      risk of ESRD, and there was a significant association between chemerin and vaspin
      variants with plasma MDA level in a sample of the Iranian population.

PMID- 29644924
TI  - Role of Prion protein-EGFR multimolecular complex during neuronal differentiation
      of human dental pulp-derived stem cells.
AB  - Cellular prion protein (PrPC) is expressed in a wide variety of stem cells in
      which regulates their self-renewal as well as differentiation potential. In this
      study we investigated the presence of PrPC in human dental pulp-derived stem
      cells (hDPSCs) and its role in neuronal differentiation process. We show that
      hDPSCs expresses early PrPC at low concentration and its expression increases
      after two weeks of treatment with EGF/bFGF. Then, we analyzed the association of
      PrPC with gangliosides and EGF receptor (EGF-R) during neuronal differentiation
      process. PrPC associates constitutively with GM2 in control hDPSCs and with GD3
      only after neuronal differentiation. Otherwise, EGF-R associates weakly in
      control hDPSCs and more markedly after neuronal differentiation. To analyze the
      functional role of PrPC in the signal pathway mediated by EGF/EGF-R, a siRNA PrP
      was applied to ablate PrPC and its function. The treatment with siRNA PrP
      significantly prevented Akt and ERK1/2 phosphorylation induced by EGF. Moreover,
      siRNA PrP treatment significantly prevented neuronal-specific antigens expression
      induced by EGF/bFGF, indicating that cellular prion protein is essential for
      EGF/bFGF-induced hDPSCs differentiation. These results suggest that PrPC interact
      with EGF-R within lipid rafts, playing a role in the multimolecular signaling
      complexes involved in hDPSCs neuronal differentiation.

PMID- 29644925
TI  - Suicide in Black children.

PMID- 29644926
TI  - Role of Ligands of Receptor for Advanced Glycation End Products (RAGE) in
      Peripheral Artery Disease.
AB  - Atherosclerotic cardiovascular disease, including peripheral artery disease
      (PAD), is more common and severe in diabetic patients compared with nondiabetic
      individuals. Indeed, diabetes is associated with the increased risk of limb
      amputation and all-cause mortality in patients with symptomatic PAD. Proteins and
      lipids are nonenzymatically modified by sugars, resulting in the formation and
      accumulation of advanced glycation end products (AGEs), whose process is
      accelerated under diabetic conditions, especially patients with a long duration
      of diabetes. Accumulating evidence shows that nonenzymatic modification by sugars
      alters the structural integrity of collagens and lipoproteins in large vessels,
      thereby being involved in vascular stiffness and atherosclerotic plaque
      instability. Furthermore, engagement of receptor for AGEs (RAGE) with its
      ligands, such as AGEs, high mobility group box 1, and S100A proteins evokes
      inflammatory and thrombotic reactions, thus playing a central role in the
      development and progression of atherosclerotic cardiovascular disease. In this
      article, we review the pathophysiological role of RAGE ligands in PAD and discuss
      the clinical utility of measurement of plasma, serum, or tissue RAGE ligands for
      assessment of the severity and prognosis of PAD. This review suggests that RAGE
      ligands may be a novel biomarker and also a therapeutic target of PAD, especially
      in patients with diabetes.

PMID- 29644927
TI  - Disease-specific clinical pathways - are they feasible in primary care? A mixed
      methods study.
AB  - OBJECTIVE: To explore the feasibility of disease-specific clinical pathways when
      used in primary care. DESIGN: A mixed-method sequential exploratory design was
      used. First, merging and exploring quality interview data across two cases of
      collaboration between the specialist care and primary care on the introduction of
      clinical pathways for four selected chronic diseases. Secondly, using
      quantitative data covering a population of 214,700 to validate and test
      hypothesis derived from the qualitative findings. SETTING: Primary care and
      specialist care collaborating to manage care coordination. RESULTS: Primary-care
      representatives expressed that their patients often have complex health and
      social needs that clinical pathways guidelines seldom consider. The
      representatives experienced that COPD, heart failure, stroke and hip fracture,
      frequently seen in hospitals, appear in low numbers in primary care. The
      quantitative study confirmed the extensive complexity among home healthcare
      nursing patients and demonstrated that, for each of the four selected diagnoses,
      a homecare nurse on average is responsible for preparing reception of the patient
      at home after discharge from hospital, less often than every other year.
      CONCLUSIONS: The feasibility of disease-specific pathways in primary care is
      limited, both from a clinical and organisational perspective, for patients with
      complex needs. The low prevalence in primary care of patients with important
      chronic conditions, needing coordinated care after hospital discharge, constricts
      transferring tasks from specialist care. Generic clinical pathways are likely to
      be more feasible and efficient for patients in this setting. Key points Clinical
      pathways in hospitals apply to single-disease guidelines, while more than 90% of
      the patients discharged to community health care for follow-up have
      multimorbidity. Primary care has to manage the health care of the patient
      holistically, with all his or her complex needs. Patients most frequently
      admitted to hospitals, i.e. patients with COPD, heart failure, stroke and hip
      fracture are infrequent in primary care and represent a minority among patients
      in need of coordinated community health care. In primary care, the low rate of
      receiving patients discharged from hospitals of major chronic diseases hampers
      maintenance of required specific skills, thus constricting the transfer of tasks
      to primary care. Generic clinical pathways are suggested to be more feasible than
      disease-specific pathways for most patients with complex needs.

PMID- 29644928
TI  - Salivary gland ultrasound is linked to the autoimmunity profile in patients with
      primary Sjogren's syndrome.
AB  - Objective Salivary gland ultrasound (SGU) is a reliable technique for assessing
      the salivary glands in patients with primary Sjogren's syndrome (pSS). The aim of
      this study was to elucidate the relationship between SGU findings and
      autoimmunity in patients with pSS. Methods Patients with pSS underwent an SGU
      assessment. The patients were classified into three groups according to their
      autoimmunity profile: the complete positive group (positive rheumatoid factor,
      antinuclear antibodies, and anti-Ro/anti-La antibodies), the partial seropositive
      group (positivity of at least one autoantibody but not all), and the seronegative
      group. Results In total, 93 patients were evaluated. Eighty-six (92.5%) were
      female, and their median age was 49.5 years. The median disease duration was 12.3
      years. Pathological SGU findings were present in 32 (34.4%) patients [25 of 36
      (78.1%) in the complete positive group and 7 of 44 (21.9%) in the partial
      positive group]. Patients with pathological SGU findings had a shorter disease
      duration and slightly higher European League Against Rheumatism Sjogren's
      syndrome disease activity index. Conclusions The autoimmunity profile and
      pathological SGU findings are strongly associated with each other in patients
      with pSS. However, the disease duration does not seem to be related to
      pathological SGU findings.

PMID- 29644929
TI  - Children with two homes: Psychological problems in relation to living
      arrangements in Nordic 2- to 9-year-olds.
AB  - AIM: Joint physical custody, children spending equal time in each parents'
      respective home after a parental divorce, is particularly common in Nordic
      compared with other Western countries. Older children have been shown to fare
      well in this practice but for young children there are few existing studies. The
      aim of this paper is to study psychological problems in 2- to 9-year-old Nordic
      children in different family forms. METHODS: Total symptom score according to the
      Strengths and Difficulties Questionnaire as well as scores showing externalizing
      problems were compared among 152 children in joint physical custody, 303 in
      single care and 3207 in nuclear families through multiple linear regression
      analyses. RESULTS: Children in single care had more psychological symptoms than
      those in joint physical custody (B = 1.08; 95% CI 0.48 to 1.67) and those in
      nuclear families had the least reported symptoms (B = -0.53; 95% CI -0.89 to 
      0.17). Externalizing problems were also lower in nuclear families (B = -0.28, 95%
      CI -0.52 to -0.04) compared with joint physical custody after adjusting for
      covariates. CONCLUSIONS: Young children with non-cohabiting parents suffered from
      more psychological problems than those in intact families. Children in joint
      physical custody had a lower total problem score than those in single care after
      adjusting for covariates. Longitudinal studies with information on family factors
      before the separation are needed to inform policy of young children's post
      separation living arrangements.

PMID- 29644930
TI  - Child and Parent Access to Transplant Information and Involvement in Treatment
      Decision Making.
AB  - Pediatric stem cell transplant processes require information sharing among the
      patient, family, and clinicians regarding the child's condition, prognosis, and
      transplant procedures. To learn about perceived access to transplant information
      and involvement in decision making among child family members (9-22 years old),
      we completed a secondary analysis of 119 interviews conducted with pediatric
      patients, sibling donors, nondonor siblings/cousins, and guardians from 27
      families prior to transplant. Perceptions of information access and involvement
      in transplant-related decisions were extracted and summarized. We compared child
      member perceptions to their guardians' and examined differences by child age and
      gender. Most child members perceived exclusion from transplant (79%) and donor
      (63%) information and decisions (63%) although this varied by child role. Gender
      was unrelated to involvement; older age was associated with less perceived
      exclusion. Congruence in perspectives across children and guardians was evident
      for eight (30%) families, most of whom ( n = 7) excluded the children.

PMID- 29644931
TI  - An Evaluation of a Diabetes Self-Management Education (DSME) Intervention
      Delivered Using Avatar-Based Technology: Certified Diabetes Educators' Ratings
      and Perceptions.
AB  - Purpose The purpose of this study was to evaluate the perceptions that certified
      diabetes educators (CDEs), of diverse health professions, have of a culturally
      appropriate e-health intervention that used avatar-based technology. Methods
      Cross-sectional, survey-based design using quantitative and qualitative
      paradigms. A logic model framed the study, which centered on the broad and
      general concepts leading to study outcomes. In total, 198 CDEs participated in
      the evaluation. Participants were mostly female and represented an age range of
      26 to 76 years. The profession representative of the sample was registered
      nurses. Study setting and data collection occurred at
      https://www.surveymonkey.com/r/AvatarVideoSurvey-for-Certified_Diabetes_Educators
      . Study instruments used were the Basic Demographics Survey (BD-13), Educational
      Material Use and Rating of Quality Scale (EMU-ROQ-9), Marlowe-Crowne Social
      Desirability Survey (MS-SOC-DES-CDE-13), Quality of Avatar Video Rating Scale
      (QAVRS-7), Recommend Avatar to Patients Scale (RAVTPS-3), Recommend Avatar Video
      to Health Professionals Scale (RAVTHP-3), and Avatar Video Applications Scale
      (AVAPP-1). Statistical analysis used included t tests, Pearson product moment
      correlations, backward stepwise regression, and content/thematic analysis.
      Results Age, ethnicity, Arab/Middle Eastern, Asian, and white/European descents
      were significant predictors of a high-quality rating of the video. Thematic and
      content analysis of the data revealed an overall positive perception of the
      video. Conclusions An e-health intervention grounded in evidence-based health
      behavior theories has potential to increase access to diabetes self-management
      education as evidenced in the ratings and perceptions of the video by CDEs.

PMID- 29644932
TI  - The Starr County Border Health Initiative: Focus Groups on Diabetes Prevention in
      Mexican Americans.
AB  - Purpose The purpose of the study was to conduct focus groups with Mexican
      Americans in an impoverished rural community on the Texas-Mexico border to
      identify current barriers to adopting healthier lifestyles and to obtain
      recommendations for diabetes prevention. Methods Three separate 2-hour focus
      groups were led by an experienced bilingual Mexican American moderator.
      Interviews included questions about cultural factors and barriers that influence
      lifestyle behaviors, aspects of previous diabetes self-management interventions
      that were helpful for motivating behavioral change, and recommendations for
      diabetes prevention. Results Twenty-seven participants attended a focus group
      session; each session involved 7 to 12 informants. Individuals were diagnosed
      with prediabetes or type 2 diabetes mellitus; most were female, foreign born, and
      Spanish speaking. Interviews documented the cultural importance of food.
      Informants raised priority issues for diabetes prevention, including the need to
      learn how to prepare healthier foods and track caloric intake. Major barriers to
      healthier lifestyles included high costs of healthy foods, fatigue from busy
      schedules and working multiple jobs, a cultural view that exercise is a waste of
      valuable time, and fear of deportation. Conclusions Cultural influences and
      barriers to implementing healthy lifestyles should be assessed regularly and
      strategies implemented to overcome them. Such factors may change as
      environmental, sociocultural, and political environments change.

PMID- 29644933
TI  - Grip strength of occupational workers in relation to carpal tunnel syndrome and
      individual factors.
AB  - The main objective of this study was to determine the association of grip
      strength with carpal tunnel syndrome (CTS) for occupational workers exposed to
      the risk of CTS. Experiments were performed on 60 workers, 15 each from four
      occupations. Grip strength was measured using a hand dynamometer.
      Electrophysiological experiments were conducted to measure CTS. Three levels of
      CTS were identified on the basis of latency value and motor nerve conduction
      velocity, viz., mild, moderate and severe. Statistical results suggest that
      workers who have CTS lose their grip strength, and higher levels of CTS lead to
      greater reduction in the grip strength. Another objective of the article was to
      investigate the association of grip strength with three individual factors of
      occupational workers, viz., body mass index, age and work experience. It is
      statistically inferred using Fisher's exact test that grip strength is not
      associated with any of these individual factors.

PMID- 29644934
TI  - Management of Subclinical Hypothyroidism in Pregnancy: A Comment from the Italian
      Society of Endocrinology and the Italian Thyroid Association to the 2017 American
      Thyroid Association Guidelines-"The Italian Way".
AB  - The 2017 American Thyroid Association guidelines for the diagnosis and management
      of thyroid disease during pregnancy and the postpartum were published six years
      after the previous ones. They provide comprehensive clinical recommendations for
      the whole spectrum of thyroid diseases, as well as for optimal iodine intake
      during pregnancy, postpartum, and lactation. The present position statement
      mainly regards the recommended flow chart for therapeutic decision making in
      pregnant women being diagnosed with subclinical hypothyroidism. Here, we comment
      on the major biochemical and clinical situations and the corresponding
      therapeutic recommendations. In particular, we welcome the critical revision of
      the thyrotropin (TSH) reference range in pregnancy, and we agree that there is no
      need to treat thyroid peroxidase antibody-negative women with a serum TSH ranging
      from 2.5 MUIU/mL to the upper limit of the reference range. This recommendation
      will hopefully reduce the huge proportion of healthy pregnant women in whom,
      according to the previous guidelines, levothyroxine therapy had to be initiated.
      On the other hand, we are concerned with the recommendation to only "consider
      treatment" in thyroid peroxidase antibody-negative pregnant women with a serum
      TSH ranging from the upper limit of the reference range to 10.0 MUIU/mL. This is
      because thyroid antibodies may be falsely negative during gestation, and serum
      negative chronic autoimmune thyroiditis is a well-known clinical entity even
      outside pregnancy. Based on these and other arguments, we recommend treatment
      with levothyroxine in pregnant women with TSH levels ranging between the upper
      limit of the reference range and 10.0 MUIU/mL independently from their thyroid
      antibody status.

PMID- 29644935
TI  - Longitudinal prospective associations between psychological symptoms and heavy
      episodic drinking from adolescence to midlife.
AB  - AIM: This study examined whether development of psychological symptoms (PS)
      differed between persons with different longitudinal profiles of heavy episodic
      drinking (HED) from adolescence to midlife. In addition, the reciprocal
      associations between PS and HED were studied. METHODS: Participants of a Finnish
      cohort study in 1983 at age 16 ( N = 2194) were followed up at ages 22 ( N =
      1656), 32 ( N = 1471), and 42 ( N = 1334). HED was assessed with frequency of
      intoxication (16-22 years) and having six or more drinks in a session (32-42
      years). Using latent class analysis, the participants were allocated to steady
      high, increased, moderate, and steady low groups according to their longitudinal
      profiles of HED. The PS scale (16-42 years) covered five mental complaints. The
      latent growth curve of PS was estimated in the HED groups for comparisons. In
      addition, the prospective associations between symptoms and HED were examined
      using cross-lagged autoregressive models. RESULTS: PS grew from 16 to 32 years,
      but declined after that, with women having higher level of PS than men. PS
      trajectory followed a path at highest and lowest level in the steady high and
      steady low HED groups, respectively. Symptoms predicted later HED, but the
      association in the opposite direction was not found. CONCLUSIONS: The more the
      HED trajectory indicated frequent HED, the higher was the level of PS throughout
      the follow-up. Results support the self-medication hypothesis, suggesting that
      alcohol is used to ease the burden of PS. More attention should be paid to
      alcohol use of people with mental symptoms in health services.

PMID- 29644936
TI  - Support Interventions to Address Breastfeeding Challenges.

PMID- 29644937
TI  - Re: "High Thyroid Cancer Mortality Rate in Japan: A Result of Nonaggressive
      Treatment Strategy, or Just an Aging Population?" By Magner (Thyroid 2018;28:818
      819).

PMID- 29644938
TI  - Acceleration of Diabetic Wound Healing with PHD2- and miR-210-Targeting
      Oligonucleotides.
AB  - In diabetes-associated chronic wounds, the normal response to hypoxia is impaired
      and many cellular processes involved in wound healing are hindered. Central to
      the hypoxia response is hypoxia-inducible factor-1alpha (HIF-1alpha), which
      activates multiple factors that enhance wound healing by promoting cellular
      motility and proliferation, new vessel formation, and re-epithelialization.
      Prolyl hydroxylase domain-containing protein 2 (PHD2) regulates HIF-1alpha
      activity by targeting it for degradation under normoxia. HIF-1alpha also
      upregulates microRNA miR-210, which in turn regulates proteins involved in cell
      cycle control, DNA repair, and mitochondrial respiration in ways that are
      antagonistic to wound repair. We have identified a highly potent short synthetic
      hairpin RNA (sshRNA) that inhibits expression of PHD2 and an antisense
      oligonucleotide (antimiR) that inhibits miR-210. Both oligonucleotides were
      chemically modified for improved biostability and to mitigate potential
      immunostimulatory effects. Using the sshRNA to silence PHD2 transcripts
      stabilizes HIF-1alpha and, in combination with the antimiR targeting miR-210,
      increases proliferation and migration of keratinocytes in vitro. To assess
      activity and delivery in an impaired wound healing model in diabetic mice, PHD2
      targeting sshRNAs and miR-210 antimiRs both alone and in combination were
      formulated for local delivery to wounds using layer-by-layer (LbL) technology.
      LbL nanofabrication was applied to incorporate sshRNA into a thin polymer coating
      on a Tegaderm mesh. This coating gradually degrades under physiological
      conditions, releasing sshRNA and antimiR for sustained cellular uptake.
      Formulated treatments were applied directly to splinted full-thickness excisional
      wounds in db/db mice. Cellular uptake was confirmed using fluorescent sshRNA.
      Wounds treated with a single application of PHD2 sshRNA or antimiR-210 closed 4
      days faster than untreated wounds, and wounds treated with both oligonucleotides
      closed on average 4.75 days faster. Markers for neovascularization and cell
      proliferation (CD31 and Ki67, respectively) were increased in the wound area
      following treatment, and vascular endothelial growth factor (VEGF) was increased
      in sshRNA-treated wounds. Our results suggest that silencing of PHD2 and miR-210
      either together or separately by localized delivery of sshRNAs and antimiRs is a
      promising approach for the treatment of chronic wounds, with the potential for
      rapid clinical translation.

PMID- 29644939
TI  - Activation of the Wnt/beta-Catenin Pathway by an Inflammatory Microenvironment
      Affects the Myogenic Differentiation Capacity of Human Laryngeal Mucosa
      Mesenchymal Stromal Cells.
AB  - Various microenvironments influence the multiple differentiation potential of
      mesenchymal stromal cells. For example, inflammatory microenvironment can
      suppress the myogenic differentiation capability of laryngeal mucosa mesenchymal
      stromal cells (LM-MSCs). The present study therefore sought to identify the
      underlying molecular mechanisms regulating these processes. We isolated a novel
      population of MSCs, LM-MSCs, from the laryngeal mucosa tissues. The cells were
      cultured in osteogenic, adipogenic, and myogenic differentiation media in the
      presence or absence of interleukin-1beta and tumor necrosis factor alpha (to
      simulate inflammatory microenvironment). The expression of active beta-catenin, p
      GSK3beta, and GSK3beta were detected by western blot and real-time polymerase
      chain reaction. The myogenic differentiation of LM-MSCs in inflammatory
      microenvironment and the regulation by Dickkopf-1 (DKK1) were tested both in vivo
      and in vitro. Inflammatory microenvironment could suppress the osteogenesis,
      adipogenesis, and myogenesis of LM-MSCs. The Wnt/beta-catenin signaling pathway
      was activated during myogenesis in inflammatory microenvironment. The suppressed
      myogenic differentiation capability of LM-MSCs in inflammatory microenvironment
      was reversed by DKK1. By regulating the Wnt/beta-catenin signaling pathway, DKK1
      can improve the myogenic differentiation of LM-MSCs in inflammatory
      microenvironment. Thus, the results of this study may help improve the efficacy
      of LM-MSCs injection therapy for vocal fold regeneration.

PMID- 29644941
TI  - Role of MicroRNAs in Treatment Response in Prostate Cancer.
AB  - Prostate cancer (PCa) is the most common non-skin cancer in men worldwide,
      resulting in significant mortality and morbidity. Depending on the grade and
      stage of the cancer, patients may be given radiation therapy, hormonal therapy,
      or chemotherapy. However, more than half these patients develop resistance to
      treatment, leading to disease progression and metastases, often with lethal
      consequences. MicroRNAs (miRNAs) are short, non-coding RNAs, which regulate
      numerous physiological as well as pathological processes, including cancer.
      miRNAs mediate their regulatory effect predominately by binding to the 3c
      untranslated region (UTR) of their target mRNAs. In this review, we will describe
      the mechanisms by which miRNAs mediate resistance to radiation and drug therapy
      (i.e. hormone therapy and chemotherapy) in PCa, including control of apoptosis,
      cell growth and proliferation, autophagy, epithelial-to-mesenchymal transition
      (EMT), invasion and metastasis, and cancer stem cells (CSCs). Furthermore, we
      will discuss the utility of circulating miRNAs isolated from different body
      fluids of prostate cancer patients as non-invasive biomarkers of cancer
      detection, disease progression, and therapy response. Finally, we will shortlist
      the candidate miRNAs, which may have a role in drug- and radioresistance, that
      could potentially be used as predictive biomarkers of treatment response.

PMID- 29644940
TI  - Transient Scleraxis Overexpression Combined with Cyclic Strain Enhances Ligament
      Cell Differentiation.
AB  - Efforts to generate tissue-engineered anterior cruciate ligament replacements are
      limited by a lack of methods to derive mature ligament cells. Viral
      overexpression of the tendon/ligament marker scleraxis (Scx) can drive cell
      differentiation; however, the use of viral vectors hampers translation to
      clinical use. In this study, C3H10T1/2 cells were transiently transfected with
      expression vectors containing the full-length murine Scx cDNA and cultured in
      three-dimensional collagen hydrogels under static or cyclic strain for up to 14
      days. beta-galactosidase (LacZ) transfected cells served as controls. Cell
      morphology and gene expression for ligament-related genes, in addition to
      contraction (hydrogel width), mechanical properties, and glycosaminoglycan (GAG)
      and DNA content of hydrogels, were quantified and compared over time, between Scx
      and LacZ groups, and between static and cyclically strained constructs. Increased
      Scx expression was maintained for the entire 14-day study in both static and
      cyclically strained constructs. In static culture, overexpression of Scx resulted
      in greater cell elongation and construct contraction compared to LacZ controls.
      There were no differences in gene expression, DNA, or GAG content between Scx and
      LacZ constructs cultured under static conditions and no differences in DNA
      content between Scx and LacZ constructs. When exposed to cyclic strain, Scx
      overexpressing cells maintained the elongated phenotype exhibited in static
      constructs, increased GAG production compared to static culture, and increased
      expression of the ligament-related genes collagen type I, decorin, and tenascin-C
      compared to strained LacZ controls. Cyclically strained constructs containing Scx
      overexpressing cells had increased maximum load and stiffness compared to LacZ
      controls. The maintenance of increased Scx expression throughout the 14 day study
      and subsequent increases in ligament marker gene expression and mechanical
      properties with cyclic, but not static strain, suggest that transient
      transfection may be a viable alternative to viral transduction of Scx for
      ligament engineering studies and support a synergistic effect of Scx and
      mechanical strain on driving early ligament cell differentiation.

PMID- 29644942
TI  - Postnatal undernutrition in mice causes cardiac arrhythmogenesis which is
      exacerbated when pharmacologically stressed.
AB  - Growth restriction caused by postnatal undernutrition increases risk for
      cardiovascular disease in adulthood with the potential to induce
      arrhythmogenesis. Thus, the purpose was to determine if undernutrition during
      development produced arrhythmias at rest and when stressed with dobutamine in
      adulthood. Mouse dams were fed (CON: 20% protein), or low-protein (LP: 8%) diet
      before mating. A cross-fostering model was used where pups nursed by dams fed LP
      diet in early [EUN; postnatal day (PN) 1-10], late (LUN; PN11-21) and whole (PUN;
      1-21) phases of postnatal life. Weaned pups were switched to CON diets for the
      remainder of the study (PN80). At PN80, body composition (magnetic resonance
      imaging), and quantitative electrocardiogram (ECG) measurements were obtained
      under 1% isoflurane anesthesia. After baseline ECG, an IP injection (1.5 ug/g
      body weight) of dobutamine was administered and ECG repeated. Undernutrition
      significantly (P<0.05) reduced body weight in LUN (22.68+/-0.88 g) and PUN
      (19.96+/-0.32 g) but not in CON (25.05+/-0.96 g) and EUN (25.28+/-0.9207 g). Fat
      mass decreased in all groups compared with controls (CON: 8.00+/-1.2 g, EUN:
      6.32+/-0.65 g, LUN: 5.11+/-1.1 g, PUN: 3.90+/-0.25 g). Lean mass was only
      significantly reduced in PUN (CON: 17.99+/-0.26 g, EUN: 17.78+/-0.39 g, LUN:
      17.34+/-0.33 g, PUN: 15.85+/-0.28 g). Absolute heart weights were significantly
      less from CON, with PUN having the smallest. ECG showed LUN had occurrences of
      atrial fibrillation; EUN had increases of 1st degree atrioventricular block upon
      stimulation, and PUN had increased risk for ventricular depolarization
      arrhythmias. CON did not display arrhythmias. Undernutrition in early life
      resulted in ventricular arrhythmias under stressed conditions, but undernutrition
      occurring in later postnatal life there is an increased incidence of atrial
      arrhythmias.

PMID- 29644943
TI  - Reduced Clostridium difficile Tests and Laboratory-Identified Events With a
      Computerized Clinical Decision Support Tool and Financial Incentive.
AB  - We hypothesized that a computerized clinical decision support tool for
      Clostridium difficile testing would reduce unnecessary inpatient tests, resulting
      in fewer laboratory-identified events. Census-adjusted interrupted time-series
      analyses demonstrated significant reductions of 41% fewer tests and 31% fewer
      hospital-onset C. difficile infection laboratory-identified events following this
      intervention.Infect Control Hosp Epidemiol 2018;39:737-740.

PMID- 29644944
TI  - A new heligmonellid (Nematoda) species of the genus Stilestrongylus in
      Euryoryzomys russatus (Rodentia: Sigmodontinae) in the Atlantic Forest, southern
      Brazil.
AB  - A new species of Nippostrongylinae (Nematoda: Heligmonellidae), Stilestrongylus
      rolandoi n. sp., is described from specimens collected from the small intestine
      of the rodent Euryoryzomys russatus in the Atlantic Forest (Santo Amaro da
      Imperatriz, Santa Catarina state, southern Brazil). The genus Stilestrongylus
      includes 23 species, which parasitize rodents occurring in the Neotropical
      region. Stilestrongylus aureus (Durette-Desset & Sutton, 1985) from Argentina, S.
      azarai (Durette-Desset & Sutton, 1985) from Argentina, S. flavescens (Sutton &
      Durette-Desset, 1991) from Uruguay, S. franciscanus (Digiani & Durette-Desset,
      2002) from Argentina, S. gracielae (Digiani & Durette-Desset, 2006) from
      Argentina, and S. oryzomysi (Sutton & Durette-Desset, 1991) from Argentina are
      closely related to Stilestrongylus rolandoi n. sp., all having caudal bursa
      patterns of types 1-4 in one of the lobes. Stilestrongylus rolandoi n. sp. is
      distinguished from the aforementioned species by its ray 6 being short in
      relation to rays 4 and 5, which are long and robust, and by having caudal bursa
      patterns of types 1-4 in both lobes. The new species has 27 ridges in the mid
      body in males, and 24 in females, and has one of the highest ratios of spicule
      length to body length (21-33%) in this genus.

PMID- 29644945
TI  - Quantitative evaluation of ruminal methane and carbon dioxide formation from
      formate through C-13 stable isotope analysis in a batch culture system.
AB  - Methane produced from formate is one of the important methanogensis pathways in
      the rumen. However, quantitative information of CH4 production from formate has
      been rarely reported. The aim of this study was to characterize the conversion
      rate (CR) of formic acid into CH4 and CO2 by rumen microorganisms. Ground lucerne
      hay was incubated with buffered ruminal fluid for 6, 12, 24 and 48 h. Before the
      incubation, 13C-labeled H13COOH was also supplied into the incubation bottle at a
      dose of 0, 1.5, 2.2 or 2.9 mg/g of DM substrate. There were no interactions
      (P>0.05) between dose and incubation time for all variables evaluated. When
      expressed as an absolute amount (ml in gas sample) or a relative CR (%), both
      13CH4 and 13CO2 production quadratically increased (P<0.01) with the addition of
      H13COOH. The total 13C (13CH4 and 13CO2) CR was also quadratically increased
      (P<0.01) when H13COOH was added. Moreover, formate addition linearly decreased
      (P<0.031) the concentrations of NH3-N, total and individual volatile fatty acids
      (acetate, propionate and butyrate), and quadratically decreased (P<0.014) the
      populations of protozoa, total methanogens, Methanosphaera stadtmanae,
      Methanobrevibacter ruminantium M1, Methanobrevibacter smithii and Methanosarcina
      barkeri. In summary, formate affects ruminal fermentation and methanogenesis, as
      well as the rumen microbiome, in particular microorganisms which are directly or
      indirectly involved in ruminal methanogenesis. This study provides quantitative
      verification for the rapid dissimilation of formate into CH4 and CO2 by rumen
      microorganisms.

PMID- 29644946
TI  - The Incidence, Risk Factors, and Chronobiology of Acute Myocardial Infarction Ten
      Years After Hurricane Katrina.
AB  - OBJECTIVE: The purpose of this study was to investigate the 10-year impact of
      Hurricane Katrina on the incidence of acute myocardial infarction (AMI) along
      with contributing risk factors and any alteration in chronobiology of AMI.
      METHODS: A single-center, retrospective, comparison study of AMI incidence was
      performed at Tulane University Health Sciences Center from 2 years before
      Hurricane Katrina to 10 years after Hurricane Katrina. A 6-year, pre-Katrina and
      10-year, post-Katrina cohort were also compared according to pre-specified
      demographic, clinical, and chronobiological data. RESULTS: AMI incidence
      increased from 0.7% (150/21,079) to 2.8% (2,341/84,751) post-Katrina (P<0.001).
      The post-Katrina cohort had higher rates of coronary artery disease (36.4% vs.
      47.9%, P=0.01), diabetes mellitus (31.3% vs. 39.9%, P=0.04), hyperlipidemia
      (45.4% vs. 59.3%, P=0.005), smoking (34.4% vs. 53.8%, P<0.001), drug abuse (10.2%
      vs. 15.4%, P=0.02), psychiatric illness (6.7% vs. 14.9%, P<0.001), medication non
      adherence (7.3% vs. 15.3%, P<0.001), and lack of employment (7.2% vs. 16.4%,
      P<0.001). The post-Katrina group had increased rates of AMI during nights (29.8%
      vs. 47.8%, P<0.001) and weekends (16.1% vs. 29.1%, P<0.001). CONCLUSIONS: Even 10
      years after the storm, Hurricane Katrina continues to be associated with
      increased incidence of AMI, higher prevalence of traditional cardiovascular and
      psychosocial risk factors, and an altered chronobiology of AMI toward nights and
      weekends. (Disaster Med Public Health Preparedness. 2018;page 1 of 6).

PMID- 29644948
TI  - Peer support and global mental health.

PMID- 29644947
TI  - Intracranial Electroencephalographic Monitoring: From Subdural to Depth
      Electrodes.
AB  - At the London Health Sciences Centre Epilepsy Program, stereotactically implanted
      depth electrodes have largely replaced subdural electrodes in the presurgical
      investigation of patients with drug-resistant epilepsy over the past 4 years. The
      rationale for this paradigm shift was more experience with, and improved surgical
      techniques for, stereoelectroencephalography, a possible lower-risk profile for
      depth electrodes, better patient tolerability, shorter operative time, as well as
      increased recognition of potential surgical targets that are not accessible to
      subdural electrodes.

PMID- 29644949
TI  - Extrinsic iron from soil contributes to Hb regeneration of anaemic rats:
      implications for foods contaminated with soil iron.
AB  - Contamination of foods with extrinsic (soil) Fe is common in developing
      countries. However, the bioavailability of this extrinsic Fe and the extent to
      which it contributes to Fe nutrition remains unknown. The present study compared
      the bioavailability of laboratory- and field-threshed teff (Eragrostisis tef
      (Zucc) Trotter) to evaluate the bioavailablity of extrinsic soil Fe that resulted
      from the traditional threshing of the staple grain. Using sequential extraction,
      Fe was fractionated and its solubility was evaluated. The contribution of the
      additional extrinsic (soil) Fe to the Hb regeneration of Fe-depleted rats was
      evaluated using a rat Hb depletion-repletion assay. Weanling male Wistar rats (n
      24) were fed Fe-deficient diet for 21 d, and were then repleted for 14 d with
      diets: either laboratory-threshed teff (35 mg Fe/kg; n 8), field-threshed teff
      (35 mg intrinsic Fe/kg+ 120 mg soil Fe/kg; n 8), or FeSO4 (control; n 8). Fe
      content of field-threshed teff (29.4 mg/100 g) was four times greater than that
      of the laboratory-threshed (6.7 mg/100 g) teff (P<0.05). Soil contamination
      significantly increased the exchangeable, acid-soluble and reducible fractions
      obtained after sequential extraction. The relative biological value of the field
      threshed teff (88 %) was higher than that of the laboratory-threshed (68 %) teff
      (P<0.05). Soil Fe can contribute to Hb regeneration in Fe-deficient rats.
      Considering that contamination of foods with soil is common in Ethiopia and other
      developing countries, it needs to be accounted for in the design and
      implementation of fortification programmes to prevent excessive intakes. Human
      studies are needed to confirm the present findings.

PMID- 29644950
TI  - Vitamin C intake in relation to bone mineral density and risk of hip fracture and
      osteoporosis: a systematic review and meta-analysis of observational studies.
AB  - We aimed to systematically review available data on the association between
      vitamin C intake and bone mineral density (BMD), as well as risk of fractures and
      osteoporosis, and to summarise this information through a meta-analysis. Previous
      studies on vitamin C intake in relation to BMD and risk of fracture and
      osteoporosis were selected through searching PubMed, Scopus, ISI Web of Science
      and Google Scholar databases before February 2017, using MeSH and text words. To
      pool data, either a fixed-effects model or a random-effects model was used, and
      for assessing heterogeneity, Cochran's Q and I 2 tests were used. Subgroup
      analysis was applied to define possible sources of heterogeneity. Greater dietary
      vitamin C intake was positively associated with BMD at femoral neck (pooled r
      0.18; 0.06, 0.30) and lumbar spine (pooled r 0.14; 95 % CI 0.06, 0.22); however,
      significant between-study heterogeneity was found at femoral neck: I 2=87.6 %, P
      heterogeneity<0.001. In addition, we found a non-significant association between
      dietary vitamin C intake and the risk of hip fracture (overall relative
      risk=0.74; 95 % CI 0.51, 1.08). Significant between-study heterogeneity was found
      (I 2=79.1 %, P heterogeneity<0.001), and subgroup analysis indicated that study
      design, sex and age were the main sources of heterogeneity. Greater dietary
      vitamin C intake was associated with a 33 % lower risk of osteoporosis (overall
      relative risk=0.67; 95 % CI 0.47, 0.94). Greater dietary vitamin C intake was
      associated with a lower risk of hip fracture and osteoporosis, as well as higher
      BMD, at femoral neck and lumbar spine.

PMID- 29644951
TI  - Vitamin D deficiency and insufficiency among US adults: prevalence, predictors
      and clinical implications.
AB  - Vitamin D deficiency (VDD) and insufficiency (VDI) are increasing at a global
      level, and they are associated with increased risk of various diseases. However,
      little information is available on the prevalence and predictors of VDD and VDI
      in a representative population of US adults. Serum 25-hydroxyvitamin D (25(OH)D)
      measurements were collected from 26 010 adults aged >=18 years from the National
      Health and Nutrition Examination Survey (NHANES) 2001-2010. Using thresholds
      recommended by the Endocrine Society, VDD was defined as 25(OH)D<50 nmol/l and
      VDI as 50<=25(OH)D<75 nmol/l. Weighted multinomial log-binomial regression was
      conducted to estimate prevalence ratios of VDD and VDI. The prevalences of VDD
      and VDI in 2001-2010 were 28.9 and 41.4 %, respectively. Adults who were black,
      less educated, poor, obese, current smokers, physically inactive and infrequent
      milk consumers had a higher prevalence of VDD. After adjustment for other
      potential predictors, obese adults showed 3.09 times higher prevalence of VDD and
      1.80 times higher prevalence of VDI than non-obese adults. Physically inactive
      adults had 2.00 and 1.36 times higher prevalence of VDD and VDI than active
      peers. Compared with frequent consumers, rare consumers of milk had 2.44 and 1.25
      times higher prevalence of VDD and VDI, respectively. Current alcohol drinkers
      had 38 % lower prevalence of VDD than non-drinkers. Awareness of the high
      prevalence of VDD and VDI among US adults and related predictors could inform
      behavioural and dietary strategies for preventing VDD and monitoring VDI,
      especially in old, black, obese and inactive individuals who report rare
      consumption of milk.

PMID- 29644952
TI  - Carbohydrate, dietary glycaemic index and glycaemic load, and colorectal cancer
      risk: a case-control study in China.
AB  - A carbohydrate-rich diet results in hyperglycaemia and hyperinsulinaemia; it may
      further induce the carcinogenesis of colorectal cancer. However, epidemiological
      evidence among Chinese population is quite limited. The aim of this study was to
      investigate total carbohydrate, non-fibre carbohydrate, total fibre, starch,
      dietary glycaemic index (GI) and glycaemic load (GL) in relation to colorectal
      cancer risk in Chinese population. A case-control study was conducted from July
      2010 to April 2017, recruiting 1944 eligible colorectal cancer cases and 2027 age
      (5-year interval) and sex frequency-matched controls. Dietary information was
      collected by using a validated FFQ. The OR and 95 % CI of colorectal cancer risk
      were assessed by multivariable logistic regression models. There was no clear
      association between total carbohydrate intake and colorectal cancer risk. The
      adjusted OR was 0.85 (95 % CI 0.70, 1.03, P trend=0.08) comparing the highest
      with the lowest quartile. Total fibre was related to a 53 % reduction in
      colorectal cancer risk (adjusted ORquartile 4 v. 1 0.47; 95 % CI 0.39, 0.58).
      However, dietary GI was positively associated with colorectal cancer risk, with
      an adjusted ORquartile 4 v. 1 of 3.10 (95 % CI 2.51, 3.85). No significant
      association was found between the intakes of non-fibre carbohydrate, starch and
      dietary GL and colorectal cancer risk. This study indicated that dietary GI was
      positively associated with colorectal cancer risk, but no evidence supported that
      total carbohydrate, non-fibre carbohydrate, starch or high dietary GL intake were
      related to an increased risk of colorectal cancer in a Chinese population.

PMID- 29644953
TI  - Dietary patterns and cardiometabolic risk factors among adolescents: systematic
      review and meta-analysis.
AB  - This study systematised and synthesised the results of observational studies that
      were aimed at supporting the association between dietary patterns and
      cardiometabolic risk (CMR) factors among adolescents. Relevant scientific
      articles were searched in PUBMED, EMBASE, SCIENCE DIRECT, LILACS, WEB OF SCIENCE
      and SCOPUS. Observational studies that included the measurement of any CMR factor
      in healthy adolescents and dietary patterns were included. The search strategy
      retained nineteen articles for qualitative analysis. Among retained articles, the
      effects of dietary pattern on the means of BMI (n 18), waist circumference (WC)
      (n 9), systolic blood pressure (n 7), diastolic blood pressure (n 6), blood
      glucose (n 5) and lipid profile (n 5) were examined. Systematised evidence showed
      that an unhealthy dietary pattern appears to be associated with poor mean values
      of CMR factors among adolescents. However, evidence of a protective effect of
      healthier dietary patterns in this group remains unclear. Considering the number
      of studies with available information, a meta-analysis of anthropometric measures
      showed that dietary patterns characterised by the highest intake of unhealthy
      foods resulted in a higher mean BMI (0.57 kg/m2; 95 % CI 0.51, 0.63) and WC (0.57
      cm; 95 % CI 0.47, 0.67) compared with low intake of unhealthy foods.
      Controversially, patterns characterised by a low intake of healthy foods were
      associated with a lower mean BMI (-0.41 kg/m2; 95 % CI -0.46,-0.36) and WC (-0.43
      cm; 95 % CI -0.52,-0.33). An unhealthy dietary pattern may influence markers of
      CMR among adolescents, but considering the small number and limitations of the
      studies included, further studies are warranted to strengthen the evidence of
      this relation.

PMID- 29644954
TI  - Eating frequency is inversely associated with BMI, waist circumference and the
      proportion of body fat in Korean adults when diet quality is high, but not when
      it is low: analysis of the Fourth Korea National Health and Nutrition Examination
      Survey (KNHANES IV).
AB  - The role of eating frequency (EF) in obesity development has been debated, and
      few studies have investigated Asian populations. Diet quality might affect the
      association between EF and obesity. Therefore, we investigated the association
      between EF and obesity indicators in a representative sample of Korean adults
      with consideration to diet quality. This cross-sectional study used data of 6951
      participants aged 19-93 years (male 49.8 %, female 50.2 %) from the Fourth Korean
      National Health and Nutrition Examination Survey. EF was assessed using a
      questionnaire, and diet quality was defined as mean adequacy ratio (MAR). To
      explore the association between EF and obesity indicators, we used multiple
      linear regression analyses with and without interaction terms between diet
      quality and EF. EF was inversely associated with each obesity indicator,
      including body fat percentage (BF%), BMI and waist circumference (WC), showing a
      significant linear trend (P<0.001 for BF%, WC and BMI). In addition, the
      association between EF and each obesity indicator was significantly altered
      according to diet quality (P value of the interaction term EF*diet quality=0.008
      in the regression model for BF%, <0.001 for BMI and 0.043 for WC). In the
      stratified analyses according to diet quality, EF had a significant inverse
      association with BF%, WC and BMI in the high diet quality groups, but not in the
      low diet quality groups. This study suggests that EF is inversely associated with
      the obesity indicators when diet quality is high, but not when it is low in
      Korean adults.

PMID- 29644955
TI  - Relationship between plasma 25-hydroxymitamin D and leucocyte telomere length by
      sex and race in a US study - CORRIGENDUM.

PMID- 29644956
TI  - Genetic polymorphisms of key enzymes in folate metabolism affect the efficacy of
      folate therapy in patients with hyperhomocysteinaemia.
AB  - The aim of this study is to analyse the efficacy rate of folate for the treatment
      of hyperhomocysteinaemia (HHcy) and to explore how folate metabolism-related gene
      polymorphisms change its efficacy. This study also explored the effects of gene
      gene and gene-environment interactions on the efficacy of folate. A prospective
      cohort study enrolling HHcy patients was performed. The subjects were treated
      with oral folate (5 mg/d) for 90 d. We analysed the efficacy rate of folate for
      the treatment of HHcy by measuring homocysteine (Hcy) levels after treatment.
      Unconditioned logistic regression was conducted to analyse the association
      between SNP and the efficacy of folic acid therapy for HHcy. The efficacy rate of
      folate therapy for HHcy was 56.41 %. The MTHFR rs1801133 CT genotype, TT genotype
      and T allele; the MTHFR rs1801131 AC genotype, CC genotype and C allele; the MTRR
      rs1801394 GA genotype, GG genotype and G allele; and the MTRR rs162036 AG
      genotype and AG+GG genotypes were associated with the efficacy of folic acid
      therapy for HHcy (P<0.05). No association was seen between other SNP and the
      efficacy of folic acid. The optimal model of gene-gene interactions was a two
      factor interaction model including rs1801133 and rs1801394. The optimal model of
      gene-environment interaction was a three-factor interaction model including
      history of hypertension, history of CHD and rs1801133. Folate supplementation can
      effectively decrease Hcy level. However, almost half of HHcy patients failed to
      reach the normal range. The efficacy of folate therapy may be genetically
      regulated.

PMID- 29644957
TI  - A carbohydrate-reduced high-protein diet acutely decreases postprandial and
      diurnal glucose excursions in type 2 diabetes patients.
AB  - The aim of the study was to assess whether a simple substitution of carbohydrate
      in the conventionally recommended diet with protein and fat would result in a
      clinically meaningful reduction in postprandial hyperglycaemia in subjects with
      type 2 diabetes mellitus (T2DM). In all, sixteen subjects with T2DM treated with
      metformin only, fourteen male, with a median age of 65 (43-70) years, HbA1c of
      6.5 % (47 mmol/l) (5.5-8.3 % (37-67 mmol/l)) and a BMI of 30 (sd 4.4) kg/m2
      participated in the randomised, cross-over study. A carbohydrate-reduced high
      protein (CRHP) diet was compared with an iso-energetic conventional diabetes (CD)
      diet. Macronutrient contents of the CRHP/CD diets consisted of 31/54 % energy
      from carbohydrate, 29/16 % energy from protein and 40/30 % energy from fat,
      respectively. Each diet was consumed on 2 consecutive days in a randomised order.
      Postprandial glycaemia, pancreatic and gut hormones, as well as satiety, were
      evaluated at breakfast and lunch. Compared with the CD diet, the CRHP diet
      reduced postprandial AUC of glucose by 14 %, insulin by 22 % and glucose
      dependent insulinotropic polypeptide by 17 % (all P<0.001), respectively.
      Correspondingly, glucagon AUC increased by 33 % (P<0.001), cholecystokinin by 24
      % (P=0.004) and satiety scores by 7 % (P=0.035), respectively. A moderate
      reduction in carbohydrate with an increase in fat and protein in the diet,
      compared with an energy-matched CD diet, greatly reduced postprandial glucose
      excursions and resulted in increased satiety in patients with well-controlled
      T2DM.

PMID- 29644958
TI  - Dairy product subgroups and risk of type 2 diabetes.

PMID- 29644959
TI  - Dietary patterns within educational groups and their association with CHD and
      stroke in the European Prospective Investigation into Cancer and Nutrition
      Netherlands cohort.
AB  - Higher-educated people often have healthier diets, but it is unclear whether
      specific dietary patterns exist within educational groups. We therefore aimed to
      derive dietary patterns in the total population and by educational level and to
      investigate whether these patterns differed in their composition and associations
      with the incidence of fatal and non-fatal CHD and stroke. Patterns were derived
      using principal components analysis in 36 418 participants of the European
      Prospective Investigation into Cancer and Nutrition-Netherlands cohort. Self
      reported educational level was used to create three educational groups. Dietary
      intake was estimated using a validated semi-quantitative FFQ. Hazard ratios were
      estimated using Cox Proportional Hazard analysis after a mean follow-up of 16
      years. In the three educational groups, similar 'Western', 'prudent' and
      'traditional' patterns were derived as in the total population. However, with
      higher educational level a lower population-derived score for the 'Western' and
      'traditional' patterns and a higher score on the 'prudent' pattern were observed.
      These differences in distribution of the factor scores illustrate the association
      between education and food consumption. After adjustments, no differences in
      associations between population-derived dietary patterns and the incidence of CHD
      or stroke were found between the educational groups (P interaction between 0.21
      and 0.98). In conclusion, although in general population and educational groups
      derived dietary patterns did not differ, small differences between educational
      groups existed in the consumption of food groups in participants considered
      adherent to the population-derived patterns (Q4). This did not result in
      different associations with incident CHD or stroke between educational groups.

PMID- 29644960
TI  - Glucosinolate and isothiocyanate intakes are inversely associated with breast
      cancer risk: a case-control study in China.
AB  - Although previous studies have investigated the association of cruciferous
      vegetable consumption with breast cancer risk, few studies focused on the
      association between bioactive components in cruciferous vegetables,
      glucosinolates (GSL) and isothiocyanates (ITC), and breast cancer risk. This
      study aimed to examine the association between consumption of cruciferous
      vegetables and breast cancer risk according to GSL and ITC contents in a Chinese
      population. A total of 1485 cases and 1506 controls were recruited into this case
      control study from June 2007 to March 2017. Consumption of cruciferous vegetables
      was assessed using a validated FFQ. Dietary GSL and ITC were computed by using
      two food composition databases linking GSL and ITC contents in cruciferous
      vegetables with responses to the FFQ. The OR and 95 % CI were assessed by
      unconditional logistic regression after adjusting for the potential confounders.
      Significant inverse associations were found between consumption of cruciferous
      vegetables, GSL and ITC and breast cancer risk. The adjusted OR comparing the
      highest with the lowest quartile were 0.51 (95 % CI 0.41, 0.63) for cruciferous
      vegetables, 0.54 (95 % CI 0.44, 0.67) for GSL and 0.62 (95 % CI 0.50, 0.76) for
      ITC, respectively. These inverse associations were also observed in both
      premenopausal and postmenopausal women. Subgroup analysis by hormone receptor
      status found inverse associations between cruciferous vegetables, GSL and ITC and
      both hormone-receptor-positive or hormone-receptor-negative breast cancer. This
      study indicated that consumption of cruciferous vegetables, GSL and ITC was
      inversely associated with breast cancer risk among Chinese women.

PMID- 29644961
TI  - High-intensity-exercise-induced intestinal damage is protected by fermented milk
      supplemented with whey protein, probiotic and pomegranate (Punica granatum L.).
AB  - Here we evaluated the effect of fermented milk supplemented with whey protein
      (approximately 80 % protein), probiotic (Bifidobacterium animalis subsp. lactis
      BB12) and pomegranate juice (Punica granatum L.) on the physical performance,
      intestinal motility and villi structure, inflammatory markers and intestinal
      microbiota of rats under high-intensity acute exercise. In all, twenty-four
      Wistar rats were separated into groups: control (Ctrl), supplemented (Supp),
      exercised (Exe) and exercised and supplemented (Exe+Supp). Rats in the Supp
      groups received fermented milk during 6 weeks by oral administration. At the end
      of the supplementation period, the Exe groups were submitted to high-intensity
      acute exercise on a treadmill. We found that intense acute exercise caused
      changes in the intestinal villi interspace, changes in the proportion of
      Lactobacillus species and an increase in Clostridium species, as well as a
      decrease in intestinal motility. Supplementation increased intestinal motility,
      and maintained the intestinal villi interspace and the natural microbiota
      proportions of the exercised rats. Physical performance was not improved by
      fermented milk supplementation. We conclude that the fermented milk containing
      whey protein, B. animalis (BB12) and pomegranate juice can re-establish
      intestinal microbiota and protect the animals from the undesirable effects of
      intense acute exercise.

PMID- 29644962
TI  - Effects of curcumin on performance, antioxidation, intestinal barrier and
      mitochondrial function in ducks fed corn contaminated with ochratoxin A.
AB  - Curcumin has been attributed with antioxidant, anti-inflammatory, antibacterial
      activities, and has shown highly protective effects against enteropathogenic
      bacteria and mycotoxins. Ochratoxin A (OTA) is one of the major intestinal
      pathogenic mycotoxins. The possible effect of curcumin on the alleviation of
      enterotoxicity induced by OTA is unknown. The effects of dietary curcumin
      supplementation on OTA-induced oxidative stress, intestinal barrier and
      mitochondrial dysfunctions were examined in young ducks. A total of 540 mixed-sex
      1-day-old White Pekin ducklings with initial BW (43.4+/-0.1 g) were randomly
      assigned into controls (fed only the basal diet), a group fed an OTA-contaminated
      diet (2 mg/kg feed), and a group fed the same OTA-contaminated feed plus 400
      mg/kg of curcumin. Each treatment consisted of six replicates, each containing 30
      ducklings and treatment lasted for 21 days. There was a significant decrease in
      average daily gain (ADG) and increased feed : gain caused by OTA (P<0.05);
      curcumin co-treatment prevented the decrease in BW and ADG compared with the OTA
      group (P<0.05). Histopathological and ultrastructural examination showed clear
      signs of enterotoxicity caused by OTA, but these changes were largely prevented
      by curcumin supplementation. Curcumin decreased the concentrations of interleukin
      1beta, tumor necrosis factor-alpha and malondialdehyde, and increased the
      activity of glutathione peroxidase induced by OTA in the jejunal mucosa of ducks
      (P<0.05). Additionally, curcumin increased jejunal mucosa occludin and tight
      junction protein 1 mRNA and protein levels, and decreased those of rho-associated
      protein kinase 1 (P<0.05). Notably, curcumin inhibited the increased expression
      of apoptosis-related genes, and downregulated mitochondrial transcription factors
      A, B1 and B2 caused by OTA without any effects on RNA polymerase mitochondrial
      (P<0.05). These results indicated that curcumin could protect ducks from OTA
      induced impairment of intestinal barrier function and mitochondrial integrity.

PMID- 29644963
TI  - In Memoriam: Jimmie C. Holland, MD, 1928-2017.

PMID- 29644964
TI  - Ulnar and Superficial Radial Nerve Swellings in Two Patients with Leprosy.

PMID- 29644965
TI  - Centers for Disease Control and Prevention Yellow Book 2018: Health Information
      for International Travelers.

PMID- 29644967
TI  - Treatment of hepatitis C: momentum still needed.

PMID- 29644968
TI  - Colorectal cancer in childhood cancer survivors.

PMID- 29644969
TI  - Time to reconsider liver transplantation for intrahepatic cholangiocarcinoma?

PMID- 29644966
TI  - Diagnosis and Treatment of Neurocysticercosis: 2017 Clinical Practice Guidelines
      by the Infectious Diseases Society of America (IDSA) and the American Society of
      Tropical Medicine and Hygiene (ASTMH).

PMID- 29644970
TI  - Striving for hepatitis C virus elimination or control?

PMID- 29644971
TI  - Haematopoietic stem cells in cirrhosis - Authors' reply.

PMID- 29644972
TI  - Haematopoietic stem cells in cirrhosis.

PMID- 29644977
TI  - Emerging optical methods for endoscopic surveillance of Barrett's oesophagus.
AB  - Barrett's oesophagus is an acquired metaplastic condition that predisposes
      patients to the development of oesophageal adenocarcinoma, prompting the use of
      surveillance regimes to detect early malignancy for endoscopic therapy with
      curative intent. The currently accepted surveillance regime uses white light
      endoscopy together with random biopsies, but has poor sensitivity and discards
      information from numerous light-tissue interactions that could be exploited to
      probe structural, functional, and molecular changes in the tissue. Advanced
      optical methods are now emerging that are highly sensitive to these changes and
      hold potential to improve surveillance of Barrett's oesophagus if they can be
      applied endoscopically. The next decade will see some of these exciting new
      methods applied to surveillance of Barrett's oesophagus in new device
      architectures for the first time, potentially leading to a long-awaited
      improvement in the standard of care.

PMID- 29644979
TI  - Correction to Lancet Gastroenterol Hepatol 2018; 3: 326-36.

PMID- 29644978
TI  - Unmet needs and new models for future trials in autoimmune hepatitis.
AB  - Despite advances in understanding and treatment of autoimmune hepatitis,
      important unmet clinical needs remain in both adult and paediatric patient
      populations. The evolving research landscape and assembly of large patient
      cohorts are creating unique opportunities to translate science into new therapies
      and care pathways, with the potential to substantially improve the lives of
      patients with autoimmune hepatitis. However, these areas of unmet need represent
      real challenges that need to be addressed if this vision is to be realised. In
      this Viewpoint, we outline the challenges in adult autoimmune hepatitis,
      particularly in relation to disease-modifying therapy, and trial design and
      delivery. Paediatric autoimmune hepatitis presents its own set of challenging
      problems.

PMID- 29644980
TI  - Correlation between the hierarchical structures and nanomechanical properties of
      amyloid fibrils.
AB  - Amyloid fibrils have recently been highlighted due to their excellent mechanical
      properties, which not only play a role in their biological functions but also
      imply their applications in biomimetic material design. Despite recent efforts to
      unveil how the excellent mechanical properties of amyloid fibrils originate, it
      has remained elusive how the anisotropic nanomechanical properties of
      hierarchically structured amyloid fibrils are determined. Here, we characterize
      the anisotropic nanomechanical properties of hierarchically structured amyloid
      fibrils using atomic force microscopy experiments and atomistic simulations. It
      is shown that the hierarchical structure of amyloid fibrils plays a crucial role
      in determining their radial elastic property but does not make any effect on
      their bending elastic property. This is attributed to the role of intermolecular
      force acting between the filaments (constituting the fibril) on the radial
      elastic modulus of amyloid fibrils. Our finding illustrates how the hierarchical
      structure of amyloid fibrils encodes their anisotropic nanomechanical properties.
      Our study provides key design principles of amyloid fibrils, which endow valuable
      insight into the underlying mechanisms of amyloid mechanics.

PMID- 29644982
TI  - Hybrid nanocomposites of 2D black phosphorus nanosheets encapsulated in PMMA
      polymer material: new platforms for advanced device fabrication.
AB  - Hybrid materials, containing a 2D filler embedded in a polymeric matrix, are an
      interesting platform for several applications, because of the variety of
      properties that the filler can impart to the polymer matrix when dispersed at the
      nanoscale. Moreover, novel properties could arise from the interaction between
      the two. Mostly the bulk properties of these materials have been studied so far,
      especially focusing on how the filler changes the polymeric matrix properties.
      Here we propose a complete change of perspective by using the hybrid
      nanocomposite material as a platform suitable to engineer the properties of the
      filler and to exploit its potential in the fabrication of devices. As a proof of
      concept of the versatility and the potential of the new method, we applied this
      approach to prepare black phosphorus (bP) nanocomposites through its dispersion
      in poly (methyl methacrylate). bP is a very interesting 2D material, whose
      application have so far been limited by its high reactivity to oxygen and water.
      In this respect, we show that electronic-grade bP flakes, already embedded in a
      protecting matrix since their exfoliation from the bulk material, are endowed
      with significantly increased stability and can be further processed into devices
      without degrading their properties.

PMID- 29644983
TI  - Minimizing residues and strain in 2D materials transferred from PDMS.
AB  - Integrating layered two-dimensional (2D) materials into 3D heterostructures
      offers opportunities for novel material functionalities and applications in
      electronics and photonics. In order to build the highest quality
      heterostructures, it is crucial to preserve the cleanliness and morphology of 2D
      material surfaces that come in contact with polymers such as PDMS during
      transfer. Here we report that substantial residues and up to ~0.22% compressive
      strain can be present in monolayer MoS2 transferred using PDMS. We show that a UV
      ozone pre-cleaning of the PDMS surface before exfoliation significantly reduces
      organic residues on transferred MoS2 flakes. An additional 200 ?C vacuum anneal
      after transfer efficiently removes interfacial bubbles and wrinkles as well as
      accumulated strain, thereby restoring the surface morphology of transferred
      flakes to their native state. Our recipe is important for building clean
      heterostructures of 2D materials and increasing the reproducibility and
      reliability of devices based on them.

PMID- 29644981
TI  - Collective gradient sensing and chemotaxis: modeling and recent developments.
AB  - Cells measure a vast variety of signals, from their environment's stiffness to
      chemical concentrations and gradients; physical principles strongly limit how
      accurately they can do this. However, when many cells work together, they can
      cooperate to exceed the accuracy of any single cell. In this topical review, I
      will discuss the experimental evidence showing that cells collectively sense
      gradients of many signal types, and the models and physical principles involved.
      I also propose new routes by which experiments and theory can expand our
      understanding of these problems.

PMID- 29644984
TI  - Design of a QA method to characterize submillimeter-sized PBS beam properties
      using a 2D ionization chamber array.
AB  - Pencil beam scanning (PBS) periodic quality assurance (QA) programs ensure the
      beam delivered to patients is within technical specifications. Two critical
      specifications for PBS delivery are the beam width and position. The aim of this
      study is to investigate whether a 2D ionization chamber array, such as the
      MatriXX detector (IBA Dosimetry, Schwarzenbruck, Germany), can be used to
      characterize submillimeter-sized PBS beam properties. The motivation is to use
      standard equipment, which may have pixel spacing coarser than the pencil beam
      size, and simplify QA workflow. The MatriXX pixels are cylindrical in shape with
      4.5 mm diameter and are spaced 7.62 mm from center to center. Two major effects
      limit the ability of using the MatriXX to measure the spot position and width
      accurately. The first effect is that too few pixels sample the Gaussian shaped
      pencil beam profile and the second effect is volume averaging of the Gaussian
      profile over the pixel sensitive volumes. We designed a method that overcomes
      both limitations and hence enables the use of the MatriXX to characterize sub
      millimeter-sized PBS beam properties. This method uses a cross-like irradiation
      pattern that is designed to increase the number of sampling data points and a
      modified Gaussian fitting technique to correct for volume averaging effects.
      Detector signals were calculated in this study and random noise and setup errors
      were added to simulate measured data. With the techniques developed in this work,
      the MatriXX detector can be used to characterize the position and width of sub
      millimeter, sigma  =  0.7 mm, sized pencil beams with uncertainty better than 3%
      relative to sigma. With the irradiation only covering 60% of the MatriXX, the
      position and width of sigma  =  0.9 mm sized pencil beams can be determined with
      uncertainty better than 3% relative to sigma. If one were to not use a cross-like
      irradiation pattern, then the position and width of sigma  =  3.6 mm sized pencil
      beams can be determined with uncertainty better than 3% relative to sigma. If one
      were to not use a cross-like pattern nor volume averaging corrections, then the
      position and width of sigma  =  5.0 mm sized pencil beams can be determined with
      uncertainty better than 3% relative to sigma. This work helps to simplify
      periodic QA in proton therapy because more routinely used ionization chamber
      arrays can be used to characterize narrow pencil beam properties.

PMID- 29644985
TI  - "Could I return to my life?" Integrated Narrative Nursing Model in Education
      (INNE).
AB  - BACKGROUND AND AIM: The Integrated Narrative Nursing Model (INNM) is an approach
      that integrates the qualitative methodology typical of the human sciences, with
      the quantitative methodology more often associated with the natural sciences.
      This complex model, which combines a focus on narrative with quantitative
      measures, has recently been effectively applied to the assessment of chronic
      patients. In this study, the model is applied to the planning phase of education
      (Integrated Narrative Nursing Education, INNE), and proves to be a valid
      instrument for the promotion of the current educational paradigm that is centered
      on the engagement of both the patient and the caregiver in their own path of
      care. The aim of this study is therefore to describe the nurse's strategy in the
      planning of an educational intervention by using the INNE model. METHODS: The
      case of a 70-year-old woman with pulmonary neoplasm is described at her first
      admission to Hospice. Each step conducted by the reference nurse, who uses INNE
      to record the nurse-patient narrative and collect subsequent questionnaires in
      order to create a shared educational plan, is also described. RESULTS: The
      information collected was submitted, starting from a grounded methodology to the
      following four levels of analysis: I. Needs Assessment, II. Narrative Diagnosis,
      III. Quantitative Outcome, IV. Integrated Outcome. Step IV, which is derived from
      the integration of all levels of analysis, allows a nurse to define, even
      graphically, the conceptual map of a patient's needs, resources and perspectives,
      in a completely tailored manner. CONCLUSION: The INNE model offers a valid
      methodological support for the professional who intends to educate the patient
      through an inter-subjective and engaged pathway, between the professional, their
      patient and the socio-relational context. It is a matter of adopting a complex
      vision that combines processes and methods that require a steady scientific basis
      and advanced methodological expertise with active listening and empathy - skills
      which require emotional intelligence.

PMID- 29644986
TI  - Evaluation of fatigue in patients with pancreatic cancer receiving chemotherapy
      treatment: a cross-sectional observational study.
AB  - BACKGROUND AND AIM OF THE WORK: Cancer-related fatigue (CRF) is one of the most
      common symptoms experienced by cancer patients (CPs) and negatively affects
      quality of life. Although CRF is frequently experienced, it is often
      underreported, underdiagnosed and undertreated. The objectives of this study were
      to evaluate the level of fatigue in patients with pancreatic cancer undergoing
      chemotherapy and to analyse its correlation with patients' demographic and
      clinical variables. METHODS: A cross-sectional observational study was
      implemented in the Oncology Day Hospital of a Northern Italian hospital. A sample
      of 48 patients receiving chemotherapy were evaluated through the Brief Fatigue
      Inventory Italian version (BFI-I) between 1 May and 12 October 2016. Data were
      statistically analysed. RESULTS: Most of our patients (94%) experienced fatigue.
      Women as well as patients with an age >=65 years reported more fatigue. Anemia,
      pain and a weight loss of over 16 kg in the last 6 months were significantly
      related to the perception of fatigue. Regarding life habits, smoking was related
      to high global score of BFI-I. CONCLUSIONS: In accordance with literature, our
      study suggests that fatigue is a frequent symptom influenced by many
      constitutional, clinical and environmental factors. Our results highlight the
      need for an early and regular evaluation of fatigue among cancer patients, in
      order to implement all those pharmacological and non-pharmacological
      interventions with proven efficacy in attenuating this symptom.

PMID- 29644987
TI  - Preventing and managing workplace violence against healthcare workers in
      Emergency Departments.
AB  - BACKGROUND AND AIM: Healthcare workers (HCWs) employed in Emergency Departments
      (EDs) frequently face with patients becoming violent because of long wait or
      diseases or under the influence of alcohol or drugs. Globally, workplace violence
      (WPV) in EDs is a major challenge to safety for HCWs, involving significant
      consequences to the victims, patients, and healthcare organizations. We reviewed
      the current literature with the aim to explore the topics focused on and to
      detect new evidences about approaching the issue of WPV toward HCWs in EDs.
      METHODS: A search for articles regarding WPV toward HCWs employed in EDs and
      published from January 2007 through December 2017 was performed; using
      predetermined criteria for inclusion, selected articles were reviewed and
      qualitatively assessed for the aims of the review. RESULTS: We found 60 papers
      which matched our inclusion criteria; the topics, discussed in order of frequency
      from highest to lowest, were: "Risk Assessment", "Occurrence Rates", "Risk
      Management", and "Physical/non Physical Consequences". Dementia, schizophrenia,
      anxiety, acute stress reaction, suicidal ideation, and alcohol and drug
      intoxication were found as predictors of physical violence perpetrated by
      patients against HCWs. CONCLUSION: A strategic way to the effective management of
      WPV should prioritize training courses focused on: constructing HCW-patient
      relationship, improving the workers' communication skills, accurate reporting of
      each violent incident, and improving the labor context through management
      commitment and employee involvement in WPV prevention programs. A special effort
      is required in implementing workplace design effective in minimizing stressful
      conditions in waiting rooms which turned out to be the most frequent site of
      assaults.

PMID- 29644988
TI  - A randomized comparison trial of two and four-step approaches to teaching Cardio
      Pulmonary Reanimation.
AB  - BACKGROUND AND AIM OF THE WORK: The treatment of cardiac arrest in an extra
      hospital environment improves with the increase in the number of people able to
      establish an early Cardio-Pulmonary Reanimation (CPR). The main aim of the study
      was to assess the validity of the two-step method in case of prolonged CPR.
      METHODS: A randomized comparison study was conducted in the University Nursing
      School of a Northern Italian town, during the 2015/16 academic year, among 60
      students, to teach them CPR techniques, through two different teaching methods (4
      step and the 2-step of CPR training). The effectiveness of the maneuvers
      performed on mannequins equipped with skill-meter was verified. RESULTS: Our
      study did not highlight any significant difference between the two methods of CPR
      training. The comparison between the two methods regarding their efficacy in
      practical teaching of CPR, highlighted by this study, proved the validity of both
      the 4-minute continuous method (1st method) and the 30:2 method (2nd method).
      CONCLUSIONS: The results of the study showed no differences between the 2-step
      and the 4-step methods, in the effectiveness of cardiac massage. The correct
      execution of chest compressions during a CPR is the key to increase the patient's
      chances of rescue. Research has shown that any interruption in the execution of
      chest compressions, leads to a progressive reduction of the effectiveness of
      cardiac massage, with negative consequences on the prognosis of the patient
      undergoing at CPR.

PMID- 29644989
TI  - The palliative care in dementia context: health professionals point of view about
      advantages and resistances.
AB  - BACKGROUND AND AIM: The 38/2010 law has expanded the provision of palliative care
      to patients with chronic-degenerative diseases. The ISTAT data show that 60% of
      the dying population is suffering from these diseases and could, according to the
      literature review, benefit particularly from such treatments. This study
      investigates the point of view of healthcare professionals, working in the
      context of dementia, regarding the knowledge and application of palliative care
      in the field of dementia. The focus is on the analysis of the resistance that may
      prevent the spread of palliative care, slowing the application of such care in
      different settings of terminality. METHODS: The method is a qualitative
      phenomenological approach. A grid of semi-structured interviews was created and
      was proposed to 33 health workers (18 women) who work in Health Centres or in the
      Alzheimer Nucleus of Northern Italy. RESULTS: Most operators think they
      understand palliative care, they believe it to be useful and necessary, but often
      only connect it with terminal illness. Others have a broader vision based on a
      more abstract and theoretical level than on real practical knowledge. A majority
      of respondents think that the spread of palliative care is slow and difficult
      because of the prevalence of the biomedical model that holistically and
      prejudicially hinders the introduction of new models. CONCLUSION: Appropriate
      training is the fundamental key to overcoming resistance. The professionals
      interviewed showed that they were aware of their lack of knowledge and declared
      that they had little competence in managing the complexity of long-term
      pathologies.

PMID- 29644990
TI  - Distraction Technique for pain reduction in Peripheral Venous Catheterization:
      randomized, controlled trial.
AB  - BACKGROUND AND AIM OF THE WORK: Procedural pain during Peripheral Venous
      Catheterization (PVC) is a significant issue for patients. Reducing procedure
      induced pain improves the quality of care and reduces patient discomfort. We
      aimed to compare a non-pharmacological technique (distraction) to anaesthetic
      cream (EMLA) for the reduction of procedural pain during PVC, in patients
      undergoing Computerized Tomography (CT) or Nuclear Magnetic Resonance (NMR) with
      contrast. METHODS: This is a Prospective, Randomized Controlled Trial. The study
      was carried out during the month of October 2015. A total of 72 patients
      undergoing PVC were randomly assigned to the experimental group (distraction
      technique, n=36) or control group (EMLA, n=36). After PVC, pain was evaluated by
      means of the numeric pain-rating scale (NRS). Pain perception was compared by
      means of Mann-Whitney Test. RESULTS: The average pain in the distraction group
      was 0.69 (SD+/-1.26), with a median value of 0. The average pain in the EMLA
      group was 1.86 (SD+/-1.73), with a median value of 2. The study showed a
      significant improvement from the distraction technique (U=347, p<.001, r=.42)
      with respect to the local anaesthetic in reducing pain perception.
      Conclusions/Implication for practice: Distraction is more effective than local
      anaesthetic in reducing of pain-perception during PVC insertion. This study is
      one of few comparing the distraction technique to an anaesthetic. It confirms
      that the practitioner-patient relationship is an important point in nursing
      assistance, allowing the establishment of trust with the patient and increasing
      compliance during the treatment process.

PMID- 29644991
TI  - Pain assessment in the Emergency Department. Correlation between pain rated by
      the patient and by the nurse. An observational study.
AB  - BACKGROUND AND AIM OF THE STUDY: Pain is always present in the Emergency
      Department (ED), but is often underestimated. The primary purpose of this study
      is to analyze the degree to which the intensity of pain is underestimated or
      overestimated in the perception of the nurse and the patient in the ED. The
      secondary objective of this research is to study possible factors that lead to
      these discrepancies in assessment. METHODS: The observational study was carried
      out in two Hospitals in Central Italy. The sample population was based on 130
      patients and 26 nurses. A questionnaire was given to the patients who provided
      personal data followed by information regarding their pain, including an
      assessment of the intensity of pain on a scale from 0 to 10. A similar
      questionnaire was given to the nurses. RESULTS: The average score based on the
      numeric rating scale (NRS) to assess the intensity of pain perceived by the
      patients is 6.16, while the numerical average estimated by the nurses based on
      their assessment is 5. Using the t test we found that the average between nurse
      and patient assessments was very significant. The analysis of the nurses'
      characteristics and professional experiences, age, years of employment and years
      of service in the ED are all significant variables affecting the discrepancy
      between the nurses' and patients' assessments of pain. As previous studies have
      shown, nurses tend to underestimate the degree of pain. In fact, in only 55.5% of
      the cases was there a correspondence in the evaluations of the intensity of pain
      done by nurses and patients, and in no case did the nurses' evaluation exceed
      that of the patients. CONCLUSIONS: This study reveals the persistent difficulty
      in pain management, while attempting contemporaneously to communicate the
      importance of the assessment, since adequate understanding of pain renders it
      possible to recognize and treat it.

PMID- 29644992
TI  - The lived experience of parents whose children discharged to home after cardiac
      surgery for congenital heart disease.
AB  - BACKGROUND: Congenital Heart Diseases (CHDs) afflicting children are estimated in
      8 per 1000 live births. Recent advances in surgery and medical treatments allowed
      an improvement in survival rates leading to changes in diseases management as
      chronic conditions. Parents involvement during clinical pathways is considered an
      essential component of care, but frequently they experience stress and anxiety
      conditions during the care path. These feelings are typical of the pre and peri
      operative period, however they don't disappear easily and sometimes they can
      increase after hospital discharge, affecting the family environment and its
      behaviors. AIM OF THE WORK: The purpose of this qualitative study is to examine
      the lived experience of parents during the time just after their children return
      home from hospital after undergoing surgery for CHD. METHODS: Parents were
      enrolled and interviewed as a prepositive sampling until concept saturation using
      Cohen's phenomenology approach. A quantitative approach was also applied using SF
      12 questionnaire. The study was conducted in two Italian hospitals: the Pediatric
      Heart Surgery Center of the Fondazione Toscana G. Monasterio Institute in Massa
      and the Pediatric Cardiac Surgery Center of the Federico II University Hospital
      in Naples. RESULTS: The main themes emerged after the analysis were "happiness
      and uncertainty"; "chronic psychophysical fatigue"; "the rediscovery of a strong
      link with health care professionals". CONCLUSIONS: Fully understand the life
      experience of these families will allow the implementation of targeted health
      interventions through the implementation of shared strategies and tools to reduce
      families and children discomfort after hospital discharge.

PMID- 29644993
TI  - Apparent Diffusion Coefficient to Subdivide Breast Imaging Reporting and Data
      System Magnetic Resonance Imaging (BI-RADS-MRI) Category 4 Lesions.
AB  - BACKGROUND This study aims to subdivide BI-RADS-MRI (Breast Imaging Reporting and
      Data System Magnetic Resonance Imaging) Category 4 lesions and to evaluate the
      role of Fischer's scoring system, apparent diffusion coefficient (ADC), and
      Fischer's + ADC in differential diagnosis of breast lesions. MATERIAL AND METHODS
      This study retrospectively analyzed the data of 143 patients (150 breast
      lesions), who were diagnosed by biopsy, and received dynamic contrast enhancement
      and diffusion-weighted imaging. The diagnostic efficacies of ADC, Fischer's
      scoring system, and the Fischer's + ADC were analyzed by the receiver operating
      characteristics curve. The area under the curve (AUC) was calculated. Fischer's
      scoring system and the Fischer's + ADC were used to subdivide BI-RADS Category 4
      breast lesions. RESULTS ADC value was negatively correlated with the tumor grade.
      The AUC of Fischer's + ADC (0.949) was significantly higher than that of ADC
      (0.855) and Fischer's (0.912) (P=0.0008 and 0.001, respectively). Scored by
      Fischer's scoring system, Category 4 and 5 indicated a likely malignant threshold
      with sensitivity and specificity of 98.70% and 65.75%, respectively. Scored by
      the Fischer's + ADC method, Category 4B and 4C indicated a likely malignant
      threshold with sensitivity of 97.40% and specificity of 82.19%. Kappa values were
      0.63 (ADC), 0.65 (Fischer's), and 0.80 (Fischer's + ADC), respectively. The
      positive predictive value of BI-RADS 4A, 4B, and 4C were 7.69%, 52.38% and
      89.29%, respectively. CONCLUSIONS Fischer's scoring system combined with ADC
      could reasonably subdivide Category 4 breast lesions with high specificity and
      sensitivity.

PMID- 29644994
TI  - Autoimmune hepatitis.
AB  - Autoimmune hepatitis (AIH) is a severe liver disease that affects children and
      adults worldwide. The diagnosis of AIH relies on increased serum transaminase and
      immunoglobulin G levels, presence of autoantibodies and interface hepatitis on
      liver histology. AIH arises in genetically predisposed individuals when a
      trigger, such as exposure to a virus, leads to a T cell-mediated autoimmune
      response directed against liver autoantigens; this immune response is permitted
      by inadequate regulatory immune control leading to a loss of tolerance. AIH
      responds favourably to immunosuppressive treatment, which should be started as
      soon as the diagnosis is made. Standard regimens include fairly high initial
      doses of corticosteroids (prednisone or prednisolone), which are tapered
      gradually as azathioprine is introduced. For those patients who do not respond to
      standard treatment, second-line drugs should be considered, including
      mycophenolate mofetil, calcineurin inhibitors, mechanistic target of rapamycin
      (mTOR) inhibitors and biologic agents, which should be administered only in
      specialized hepatology centres. Liver transplantation is a life-saving option for
      those who progress to end-stage liver disease, although AIH can recur or develop
      de novo after transplantation. In-depth investigation of immune pathways and
      analysis of changes to the intestinal microbiota should advance our knowledge of
      the pathogenesis of AIH and lead to novel, tailored and better tolerated
      therapies.

PMID- 29644995
TI  - Autoimmune hepatitis.

PMID- 29644996
TI  - Simultaneous lineage tracing and cell-type identification using CRISPR-Cas9
      induced genetic scars.
AB  - A key goal of developmental biology is to understand how a single cell is
      transformed into a full-grown organism comprising many different cell types.
      Single-cell RNA-sequencing (scRNA-seq) is commonly used to identify cell types in
      a tissue or organ. However, organizing the resulting taxonomy of cell types into
      lineage trees to understand the developmental origin of cells remains
      challenging. Here we present LINNAEUS (lineage tracing by nuclease-activated
      editing of ubiquitous sequences)-a strategy for simultaneous lineage tracing and
      transcriptome profiling in thousands of single cells. By combining scRNA-seq with
      computational analysis of lineage barcodes, generated by genome editing of
      transgenic reporter genes, we reconstruct developmental lineage trees in
      zebrafish larvae, and in heart, liver, pancreas, and telencephalon of adult fish.
      LINNAEUS provides a systematic approach for tracing the origin of novel cell
      types, or known cell types under different conditions.

PMID- 29644997
TI  - Highly scalable generation of DNA methylation profiles in single cells.
AB  - We present a highly scalable assay for whole-genome methylation profiling of
      single cells. We use our approach, single-cell combinatorial indexing for
      methylation analysis (sci-MET), to produce 3,282 single-cell bisulfite sequencing
      libraries and achieve read alignment rates of 68 +/- 8%. We apply sci-MET to
      discriminate the cellular identity of a mixture of three human cell lines and to
      identify excitatory and inhibitory neuronal populations from mouse cortical
      tissue.

PMID- 29644998
TI  - Fast, long-term, super-resolution imaging with Hessian structured illumination
      microscopy.
AB  - To increase the temporal resolution and maximal imaging time of super-resolution
      (SR) microscopy, we have developed a deconvolution algorithm for structured
      illumination microscopy based on Hessian matrixes (Hessian-SIM). It uses the
      continuity of biological structures in multiple dimensions as a priori knowledge
      to guide image reconstruction and attains artifact-minimized SR images with less
      than 10% of the photon dose used by conventional SIM while substantially
      outperforming current algorithms at low signal intensities. Hessian-SIM enables
      rapid imaging of moving vesicles or loops in the endoplasmic reticulum without
      motion artifacts and with a spatiotemporal resolution of 88 nm and 188 Hz. Its
      high sensitivity allows the use of sub-millisecond excitation pulses followed by
      dark recovery times to reduce photobleaching of fluorescent proteins, enabling
      hour-long time-lapse SR imaging of actin filaments in live cells. Finally, we
      observed the structural dynamics of mitochondrial cristae and structures that, to
      our knowledge, have not been observed previously, such as enlarged fusion pores
      during vesicle exocytosis.

PMID- 29644999
TI  - Novel in vitro dynamic metabolic system for predicting the human pharmacokinetics
      of tolbutamide.
AB  - Liver metabolism is commonly considered the major determinant in drug discovery
      and development. Many in vitro drug metabolic studies have been developed and
      applied to understand biotransformation. However, these methods have
      disadvantages, resulting in inconsistencies between in vivo and in vitro
      experiments. A major factor is that they are static systems that do not consider
      the transport process in the liver. Here we developed an in vitro dynamic
      metabolic system (Bio-PK metabolic system) to mimic the human pharmacokinetics of
      tolbutamide. Human liver microsomes (HLMs) encapsulated in a F127'-Acr-Bis
      hydrogel (FAB hydrogel) were placed in the incubation system. A microdialysis
      sampling technique was used to monitor the metabolic behavior of tolbutamide in
      hydrogels. The measured results in the system were used to fit the in vitro
      intrinsic clearance of tolbutamide with a mathematical model. Then, a PBPK model
      that integrated the corresponding in vitro intrinsic clearance was developed to
      verify the system. Compared to the traditional incubation method, reasonable PK
      profiles and the in vivo clearance of tolbutamide could be predicted by
      integrating the intrinsic clearance of tolbutamide obtained from the Bio-PK
      metabolic system into the PBPK model. The predicted maximum concentration (Cmax),
      area under the concentration-time curve (AUC), time to reach the maximum plasma
      concentration (Tmax) and in vivo clearance were consistent with the clinically
      observed data. This novel in vitro dynamic metabolic system can compensate for
      some limitations of traditional incubation methods; it may provide a new method
      for screening compounds and predicting pharmacokinetics in the early stages,
      supporting the development of compounds.

PMID- 29645000
TI  - Neotuberostemonine inhibits the differentiation of lung fibroblasts into
      myofibroblasts in mice by regulating HIF-1alpha signaling.
AB  - Pulmonary fibrosis may be partially the result of deregulated tissue repair in
      response to chronic hypoxia. In this study we explored the effects of hypoxia on
      lung fibroblasts and the effects of neotuberostemonine (NTS), a natural alkaloid
      isolated from Stemona tuberosa, on activation of fibroblasts in vitro and in
      vivo. PLFs (primary mouse lung fibroblasts) were activated and differentiated
      after exposure to 1% O2 or treatment with CoCl2 (100 MUmol/L), evidenced by
      markedly increased protein or mRNA expression of HIF-1alpha, TGF-beta, FGF2,
      alpha-SMA and Col-1alpha/3alpha, which was blocked after silencing HIF-1alpha,
      suggesting that the activation of fibroblasts was HIF-1alpha-dependent. NTS (0.1
      10 MUmol/L) dose-dependently suppressed hypoxia-induced activation and
      differentiation of PLFs, whereas the inhibitory effect of NTS was abolished by co
      treatment with MG132, a proteasome inhibitor. Since prolyl hydroxylation is a
      critical step in initiation of HIF-1alpha degradation, we further showed that NTS
      treatment reversed hypoxia- or CoCl2-induced reduction in expression of prolyl
      hydroxylated-HIF-1alpha. With hypoxyprobe immunofiuorescence staining, we showed
      that NTS treatment directly reversed the lower oxygen tension in hypoxia-exposed
      PLFs. In a mouse model of lung fibrosis, oral administration of NTS (30 mg.kg-1.d
      1, for 1 or 2 weeks) effectively attenuated bleomycin-induced pulmonary fibrosis
      by inhibiting the levels of HIF-1alpha and its downstream profibrotic factors
      (TGF-beta, FGF2 and alpha-SMA). Taken together, these results demonstrate that
      NTS inhibits the protein expression of HIF-1alpha and its downstream factors TGF
      beta, FGF2 and alpha-SMA both in hypoxia-exposed fibroblasts and in lung tissues
      of BLM-treated mice. NTS with anti-HIF-1alpha activity may be a promising
      pharmacological agent for the treatment of pulmonary fibrosis.

PMID- 29645001
TI  - Multiplex biomarker approach to cardiovascular diseases.
AB  - Personalized medicine is partly based on biomarker-guided diagnostics, therapy
      and prognosis, which is becoming an unavoidable concept in modern cardiology.
      However, the clinical significance of single biomarker studies is rather limited.
      A promising novel approach involves combining multiple markers into a multiplex
      panel, which could refine the management of a particular patient with
      cardiovascular pathology. Two principally different assay formats have been
      developed to facilitate simultaneous quantification of multiple antigens: planar
      array assays and microbead assays. These approaches may help to better evaluate
      the complexity and dynamic nature of pathologic processes and offer substantial
      cost and sample savings compared with traditional enzyme-linked immunosorbent
      assay (ELISA) measurements. However, a multiplex multimarker approach cannot
      become a generally disseminated method until analytical problems are solved and
      further studies confirming improved clinical outcomes are accomplished. These
      drawbacks underlie the fact that a limited number of systematic studies are
      available regarding the use of a multiplex biomarker approach in cardiovascular
      medicine to date. Our perspective underscores the significant potential of the
      use of the multiplex approach in a wider conceptual framework under the close
      cooperation of clinical and experimental cardiologists, pathophysiologists and
      biochemists so that the personalized approach based on standardized multimarker
      testing may improve the management of various cardiovascular pathologies and
      become a ubiquitous partner of population-derived evidence-based medicine.

PMID- 29645002
TI  - Proteomics analysis reveals a potential new target protein for the lipid-lowering
      effect of Berberine8998.
AB  - Berberine8998 is a newly synthesized berberine derivative with better lipid
      lowering activity and improved absorption. The objective of this study was to
      investigate the effects of berberine8998 on serum cholesterol and lipid levels in
      vivo and to examine the mechanisms involved. Hamsters on high-fat diet (HFD) were
      administered berberine or berberine8998 (50 mg.kg-1.d-1, ig) for 3 weeks.
      Berberine8998 administration significantly lowered the total cholesterol,
      triglycerides and LDL-C levels in HFD hamsters. Bioinformatics revealed that
      berberine and berberine8998 shared similar metabolic pathways and fatty acid
      metabolism was the predominant pathway. Western blot validation results showed
      that peroxisomal acyl-coenzyme A oxidase 1 (ACOX1) and long-chain fatty acid-CoA
      ligase 1 (ACSL1), two proteins involved in fatty acid metabolism, were expressed
      differently in the berberine8998 group than in the untreated group and the
      berberine treatment group. Biochemistry results showed that berberine8998
      significantly lowered the non-esterified fatty acid (NEFA) levels, which may lead
      to a reduction in TG levels in the berberine8998 treatment group and the
      differences observed in proteomics analyses. Pharmacokinetic analysis conducted
      in rats. After administration of berberine or berberine8998 (50 mg/kg, ig),
      berberine8998 exhibited a remarkably improved absorption with increasing
      bioavailability by 6.7 times compared with berberine. These findings suggest that
      berberine8998 lowers cholesterol and lipid levels via different mechanisms than
      berberine, and its improved absorption makes it a promising therapeutic candidate
      for the treatment of hypercholesterolemia and obesity.

PMID- 29645003
TI  - Selecting candidates for early discharge after radical cystectomy for bladder
      cancer.

PMID- 29645004
TI  - Is There a Relationship Between Multiple Sclerosis and Epilepsy? If So What Does
      It Tell Us About Epileptogenesis?

PMID- 29645005
TI  - Ongoing efforts to reduce perioperative morbidity of radical cystectomy: towards
      widespread adoption of extended-duration thromboprophylaxis.

PMID- 29645006
TI  - Hippocampal Depth Electrodes in Epilepsy Surgery: Diagnostic or Damaging?

PMID- 29645007
TI  - Statistical Methods for Clinical Trial Designs in the New Era of Cancer
      Treatment.
AB  - Recent success of immunotherapy and other targeted therapies in cancer treatment
      has signaled the advent of precision medicine. Unlike conventional trial designs
      that aim to find an optimal treatment ignoring inter-patient heterogeneity,
      clinical trial designs for precision medicine must take into account patients'
      variability in genes, environments, and lifestyle. This article provides a review
      of recent research development of clinical trial designs toward this trend.

PMID- 29645008
TI  - Epilepsy Surgery Works - So Why the Wait?

PMID- 29645009
TI  - Developmental plasticity research in evolution and human health: Response to
      commentaries.

PMID- 29645011
TI  - Corrigendum to "Successful use of intrapelvic Quikclot in life-threatening blast
      injury" [Trauma Case Rep. 12 (2017) 59-62].
AB  - [This corrects the article DOI: 10.1016/j.tcr.2017.10.021.].

PMID- 29645010
TI  - Adding patient-reported outcomes to a multisite registry to quantify quality of
      life and experiences of disease and treatment for youth with juvenile idiopathic
      arthritis.
AB  - Background: Children with Juvenile Idiopathic Arthritis (JIA) often have poor
      health-related quality of life (HRQOL) despite advances in treatment. Patient
      centered research may shed light on how patient experiences of treatment and
      disease contribute to HRQOL, pinpointing directions for improving care and
      enhancing outcomes. Methods: Parent proxies of youth enrolled in the Childhood
      Arthritis and Rheumatology Research Alliance (CARRA) Registry shared patient
      reported outcomes about their child's HRQOL and experiences of disease and
      treatment burden (pain interference, morning stiffness, history of medication
      side effects and methotrexate intolerance). Contributions of these measures to
      HRQOL were estimated using generalized estimating equations accounting for site
      and patient demographics. Results: Patients (N = 180) were 81.1% white non
      Hispanic and 76.7% female. Mean age was 11.8 (SD = 3.6) years, mean disease
      duration was 7.7 years (SD = 3.5). Mean Total Pediatric Quality of Life was 76.7
      (SD = 18.2). Mean pain interference score was 50.1 (SD = 11.1). Nearly one-in
      five (17.8%) youth experienced >15 min of morning stiffness on a typical day,
      more than one quarter (26.7%) reported >=1 serious medication side effect and
      among 90 methotrexate users, 42.2% met criteria for methotrexate intolerance.
      Measures of disease and treatment burden were independently negatively associated
      with HRQOL (all p-values <0.01). Negative associations among measures of
      treatment burden and HRQOL were attenuated after controlling for disease burden
      and clinical characteristics but remained significant. Conclusions: For youth
      with JIA, HRQOL is multidimensional, reflecting disease as well as treatment
      factors. Adverse treatment experiences undermine HRQOL even after accounting for
      disease symptoms and disease activity and should be assessed routinely to improve
      wellbeing.

PMID- 29645012
TI  - Utility of Satellite Remote Sensing for Land-Atmosphere Coupling and Drought
      Metrics.
AB  - Feedbacks between the land and the atmosphere can play an important role in the
      water cycle and a number of studies have quantified Land-Atmosphere (L-A)
      interactions and feedbacks through observations and prediction models. Due to the
      complex nature of L-A interactions, the observed variables are not always
      available at the needed temporal and spatial scales. This work derives the
      Coupling Drought Index (CDI) solely from satellite data and evaluates the input
      variables and the resultant CDI against in-situ data and reanalysis products.
      NASA's AQUA satellite and retrievals of soil moisture and lower tropospheric
      temperature and humidity properties are used as input. Overall, the AQUA-based
      CDI and its inputs perform well at a point, spatially, and in time (trends)
      compared to in-situ and reanalysis products. In addition, this work represents
      the first time that in-situ observations were utilized for the coupling
      classification and CDI. The combination of in-situ and satellite remote sensing
      CDI is unique and provides an observational tool for evaluating models at local
      and large scales. Overall, results indicate that there is sufficient information
      in the signal from simultaneous measurements of the land and atmosphere from
      satellite remote sensing to provide useful information for applications of
      drought monitoring and coupling metrics.

PMID- 29645013
TI  - Confronting weather and climate models with observational data from soil moisture
      networks over the United States.
AB  - Four land surface models in uncoupled and coupled configurations are compared to
      observations of daily soil moisture from 19 networks in the conterminous United
      States to determine the viability of such comparisons and explore the
      characteristics of model and observational data. First, observations are analyzed
      for error characteristics and representation of spatial and temporal variability.
      Some networks have multiple stations within an area comparable to model grid
      boxes; for those we find that aggregation of stations before calculation of
      statistics has little effect on estimates of variance, but soil moisture memory
      is sensitive to aggregation. Statistics for some networks stand out as unlike
      those of their neighbors, likely due to differences in instrumentation,
      calibration and maintenance. Buried sensors appear to have less random error than
      near-field remote sensing techniques, and heat dissipation sensors show less
      temporal variability than other types. Model soil moistures are evaluated using
      three metrics: standard deviation in time, temporal correlation (memory) and
      spatial correlation (length scale). Models do relatively well in capturing large
      scale variability of metrics across climate regimes, but poorly reproduce
      observed patterns at scales of hundreds of kilometers and smaller. Uncoupled land
      models do no better than coupled model configurations, nor do reanalyses
      outperform free-running models. Spatial decorrelation scales are found to be
      difficult to diagnose. Using data for model validation, calibration or data
      assimilation from multiple soil moisture networks with different types of sensors
      and measurement techniques requires great caution. Data from models and
      observations should be put on the same spatial and temporal scales before
      comparison.

PMID- 29645014
TI  - Interculturalism and Informed Consent: Respecting Cultural Differences without
      Breaching Human Rights.
AB  - Interventions in medicine require multicenter clinical trials on a large rather
      than limited number of subjects from various genetic and cultural backgrounds.
      International guidelines to protect the rights and well-being of human subjects
      involved in clinical trials are criticized for the priority they place on Western
      cultural values. These discussions become manifest especially with regard to the
      content and methodology of the informed consent procedure. The ethical dilemma
      emerges from the argument that there are fundamental differences about the
      concept of respect for the autonomy of individuals in different cultures and
      religions. Some communities prioritize the consent of community leaders or the
      head of family - usually men - over the voluntary and free consent of the
      individual. The aim of this work is to discuss this ethical dilemma to determine
      a base for a consensus that satisfies the sensibilities of different cultures
      without damaging the rights and autonomy of human subjects.

PMID- 29645015
TI  - Correction: The outcomes and prognostic factors of acute respiratory failure in
      the patients 90 years old and over.
AB  - [This corrects the article DOI: 10.18632/oncotarget.24051.].

PMID- 29645016
TI  - Clinical benefit to regionalization of care for muscle invasive bladder cancer.

PMID- 29645017
TI  - Downstream effects of regionalization: reconciling our predictions with the
      volume-outcome paradigm.

PMID- 29645018
TI  - Nutritional habits and bladder cancer.

PMID- 29645019
TI  - How to assess and improve health-related quality of life in bladder cancer
      patients.

PMID- 29645020
TI  - Surviving travel or travelling to survive: the association of travel distance
      with survival in muscle invasive bladder cancer.

PMID- 29645021
TI  - Correction: MicroRNA-29a increased the intestinal membrane permeability of
      colonic epithelial cells in irritable bowel syndrome rats.
AB  - [This corrects the article DOI: 10.18632/oncotarget.20687.].

PMID- 29645022
TI  - High-resolution spectral analysis of ammonia near 6.2 MUm using a cw EC-QCL
      coupled with cavity ring-down spectroscopy.
AB  - We report on the development of a mid-infrared cavity ring-down spectrometer
      (CRDS) coupled with a continuous wave (cw) external cavity quantum cascade laser
      (EC-QCL), operating between 6.0 MUm and 6.3 MUm, for high-resolution
      spectroscopic studies of ammonia (NH3) which served as a bench-mark molecule in
      this spectral region. We characterized the EC-QCL based CRDS system in detail and
      achieved a noise-equivalent absorption (NEA) coefficient of 2.11 * 10-9 cm-1 Hz
      1/2 for a 100 Hz data acquisition rate. We thereafter exploited the system for
      high-resolution spectroscopic analysis of interference-free 10 transition lines
      of the nu4 fundamental vibrational band of NH3 centred at ~6.2 MUm. We probed the
      strongest interference-free absorption line RQ(4,3) of nu4, centred at 1613.370
      cm-1 for highly-sensitive trace detection of NH3 and subsequently achieved a
      minimum detection sensitivity (1sigma) of 2.78 * 109 molecules per cm3 which
      translated into the detection limit of 740 parts-per-trillion by volume (pptv/10
      12) at a pressure of 115 Torr for an integration time of ~167 seconds. To
      demonstrate the efficacy of the present system in real-life applications, we
      finally measured the mixing ratios of NH3 present in ambient air and human
      exhaled breath with high sensitivity and molecular specificity.

PMID- 29645023
TI  - FePO4 as an anode material to obtain high-performance sodium-based dual-ion
      batteries.
AB  - Herein, the FePO4 material was for the first time proposed to serve as an anode
      electrode, as an intercalation sodium host, to obtain novel sodium-based dual-ion
      batteries. And the full cell can present a highly reversible capacity of 120 mA h
      g-1 in the range of 2-4.2 V and exhibits an excellent initial coulombic
      efficiency of 99.5%.

PMID- 29645024
TI  - F-Doped carbon nano-onion films as scaffold for highly efficient and stable Li
      metal anodes: a novel laser direct-write process.
AB  - Li metal is the most promising choice for anode in high-energy rechargeable
      batteries, but the dendrite growth upon cycling leads to safety concerns and poor
      cycle life. Herein, we demonstrate a novel and scalable approach for direct
      writing of a thin layer of carbon nano-onions on copper substrate to stabilize
      the Li metal anode and prevent the dendrite growth. The F-doped carbon nano-onion
      film (F-CNOF) scaffold enables reversible electroplating for over 1500 hours (300
      cycles) with a coulombic efficiency of ~100%. The F-CNOF is capable of depositing
      Li equivalent to a capacity of 10 mA h cm-2 (gravimetric capacity 3218 mA h g-1)
      at 1 mA cm-2, operating at a high current density of 6 mA cm-2. More importantly,
      these features of long-term cyclic stability and excellent rate capability are
      attributed to the very high curvature due to nano dimension (~108 m-1) of the
      nano-onions that develop a very uniform Li flux due to the negative surface
      charge, thus preventing the dendrite formation. We have also shown via first
      principles DFT calculations that the high curvature achieved herein can
      significantly enhance the binding energy of Li to the carbon surface, which helps
      to improve lithiophilicity. A full cell fabricated using Li4Ti5O12 as the
      positive electrode showed cyclic stability of 450 cycles.

PMID- 29645025
TI  - Dietary fish oil ameliorates adipose tissue dysfunction in insulin-resistant rats
      fed a sucrose-rich diet improving oxidative stress, peroxisome proliferator
      activated receptor gamma and uncoupling protein 2.
AB  - This work aims to assess the possible beneficial effects of dietary fish oil (FO)
      on the pre-existing adipose tissue dysfunction through the improvement or
      reversion of the mechanisms underlying oxidative stress and pro-inflammatory
      cytokines in dyslipemic insulin-resistant rats. Wistar rats were fed a sucrose
      rich diet (SRD) for 6 months. After that half of the animals continued with the
      SRD until month 8 while in the other half corn oil was replaced by FO for 2
      months (SRD + FO). A reference group consumed a control diet all the time. In an
      epididymal fat pad, we analyzed antioxidant and oxidant enzyme activities, ROS
      content, glutathione redox state, the protein level of peroxisome proliferator
      activated receptor gamma (PPARgamma) and the expression and protein levels of
      uncoupling protein 2 (UCP2) as well as oxidative stress biomarkers and TNF-alpha
      and IL-6 plasma levels. Besides these, insulin sensitivity and the composition of
      fatty acid phospholipids of adipose tissue were measured. Compared with the SRD
      the SRD + FO fed group showed a decrease of fat pad weight and the antioxidant
      and oxidant enzyme activities and ROS content returned to control values along
      with normal plasma TNF-alpha and IL-6 levels. FO normalized both the decrease of
      PPARgamma protein and the increase of protein and expression of UCP2.
      Furthermore, FO increased the n-3/n-6 fatty acid ratio in the adipose tissue
      phospholipids and normalized dyslipidemia and insulin resistance. Finally, these
      findings reinforce the view that dietary FO may exert a beneficial effect in
      ameliorating the dyslipidemia and insulin resistance in this animal model.

PMID- 29645026
TI  - Pd-catalyzed defluorination/arylation of alpha-trifluoromethyl ketones via
      consecutive beta-F elimination and C-F bond activation.
AB  - An unprecedented Pd-catalyzed activation of a CF3 group is reported herein. The
      key to the success of this reaction is the combination of consecutive beta-F
      elimination and C-F bond oxidative addition of a trifluoromethyl group. It also
      represents the first general application of alpha-trifluoromethyl ketones as
      building blocks by C-F bond activation.

PMID- 29645027
TI  - Silicon quantum dots with heavily boron and phosphorus codoped shell.
AB  - Heavily boron and phosphorus codoped silicon quantum dots (QDs) are dispersible
      in water without organic ligands and exhibit near infrared luminescence. We
      summarize the fundamental properties and demonstrate the formation of a variety
      of nanocomposites.

PMID- 29645028
TI  - Molecular structure and interactions of water intercalated in nickel hydroxide.
AB  - The structure and properties of alpha-Ni(OH)2 containing water and nitrate have
      been investigated computationally. The adsorption of water molecules on the
      Ni(OH)2 surface is also investigated to provide insight into the nature of the
      water-Ni(OH)2 interactions. The spectroscopic and dynamical behaviour of the
      intercalated species has been characterized and used to explain experimental
      findings reported for this material. The results presented here indicate that the
      water molecules interact non-covalently with Ni(OH)2, with a binding energy that
      is comparable in magnitude with that of the water dimer hydrogen bond. The
      presence of the intercalated species increases the distance between the Ni(OH)2
      layers such that the interlayer interactions are negligible. The weakening of the
      interlayer interactions facilitates the horizontal displacement of the layers
      relative to one another, providing a possible origin for stacking faults observed
      in alpha-Ni(OH)2. Comparison of the vibrational frequencies calculated here with
      the experimental spectra confirms that alpha-Ni(OH)2 containing only water
      molecules can be synthesized. The structures of the water molecules intercalated
      in alpha-Ni(OH)2 were found to be analogous to those absorbed in gamma-NiOOH,
      while the water-layer interactions are stronger in gamma-NiOOH. The results
      presented here characterize the structure and interactions of water intercalated
      in nickel hydroxides and also provide insights into the effects of intercalated
      water on the properties of layered metal hydroxides.

PMID- 29645029
TI  - Regulation of both the structure and function by a de novo designed disulfide
      bond: a case study of heme proteins in myoglobin.
AB  - A de novo designed intramolecular disulfide bond in myoglobin, resembling that in
      cytoglobin without structural evidence, was confirmed by an X-ray structure for
      the first time and was demonstrated to regulate both the structure and function
      of this protein, which fulfills the design of an artificial dehaloperoxidase,
      with an activity exceeding that of a native enzyme.

PMID- 29645030
TI  - Micellar confinement disrupts collective structure and accelerates collective
      dynamics of encapsulated water.
AB  - This computational study deals with the collective structure and dynamics as well
      as their interaction seen from a dielectric viewpoint in zwitterionic reverse
      micelles for which a force field was designed de novo. For this end, a dualistic
      strategy is followed: the raw data are generated by extensive microscopic
      molecular dynamics (MD) simulations while the subsequent analysis has a focus on
      mesoscopic dielectric properties. The unusually low dielectric signals as well as
      the remarkable acceleration of collective dynamics is elucidated in great detail.
      This structural and dynamic behaviour is caused essentially by non-specific
      micellar boundary conditions. We found that in these ion lacking reverse micelles
      the water core and the water sheath compensate each other dielectrically which
      can be understood as a LeChatelier phenomenon facilitating the transition from
      highly polar encapsulated water to the non-polar low dielectric medium octane. In
      addition, specific chemical effects are brought about by the perturbing influence
      of the surfactants. This comprehensive analysis aids both in understanding and
      designing the dipolar properties of liquid polar spherical colloids dispersed in
      a hydrophobic medium.

PMID- 29645032
TI  - Room-temperature processed films of colloidal carved rod-shaped nanocrystals of
      reduced tungsten oxide as interlayers for perovskite solar cells.
AB  - Thanks to their high stability, good optoelectronic and extraordinary
      electrochromic properties, tungsten oxides are among the most valuable yet
      underexploited materials for energy conversion applications. Herein, colloidal
      one-dimensional carved nanocrystals of reduced tungsten trioxide (WO3-x) are
      successfully integrated, for the first time, as a hole-transporting layer (HTL)
      into CH3NH3PbI3 perovskite solar cells with a planar inverted device
      architecture. Importantly, the use of such preformed nanocrystals guarantees the
      facile solution-cast-only deposition of a homogeneous WO3-x thin film at room
      temperature, allowing achievement of the highest power conversion efficiency ever
      reported for perovskite solar cells incorporating raw and un-doped tungsten oxide
      based HTL.

PMID- 29645031
TI  - Coordination chemistry within a protein host: regulation of the secondary
      coordination sphere.
AB  - Secondary coordination spheres of metal complexes are instrumental in controlling
      properties that are linked to function. To study these effects in aqueous
      solutions artificial Cu proteins have been developed using biotin-streptavidin
      (Sav) technology and their binding of external azide ions investigated. Parallel
      binding studies were done in crystallo on single crystals of the artificial Cu
      proteins. Spectroscopic changes in solution are consistent with azide binding to
      the Cu centers. Structural studies corroborate that a Cu-N3 unit is present in
      each Sav subunit and reveal the composition of hydrogen bonding (H-bonding)
      networks that include the coordinated azido ligand. The networks involve amino
      acid residues and water molecules within the secondary coordination sphere.
      Mutation of these residues to ones that cannot form H-bonds caused a measurble
      change in the equilibrium binding constants that were measured in solution. These
      findings further demonstrate the utility of biotin-Sav technology to prepare
      water-stable inorganic complexes whose structures can be controlled within both
      primary and secondary coordination spheres.

PMID- 29645033
TI  - Ion pairing in 1-butyl-3-methylpyridinium halide ionic liquids studied using NMR
      and DFT calculations.
AB  - We present the 1H, 13C and 15N NMR chemical shifts of bulk ionic liquids based on
      1-butyl-3-methylimidazolium (the cation also known as 1-butyl-3-picolinium)
      halides (Cl-, Br- and I-) and tribromide (Br3-) salts. A characterization in
      solution of the analogous ICl2- and I3- salts is also reported. A series of DFT
      calculations has been run to predict the features of the NMR spectra of the pure
      ILs based on a few selected supramolecular ionic aggregates. To test the effect
      of temperature, and vibrational and conformational motions, only for the chloride
      salt, we also run first-principles molecular dynamics simulations of the ion pair
      in the gas phase, using the ADMP scheme (Atom Centered Density Matrix Propagation
      molecular dynamics model). The aim of our investigation is to test whether a
      simple DFT based approach of ion-pairing in ionic liquids is capable of providing
      reliable results and under which conditions the protocol is robust. We obtained a
      very good agreement between the calculated and experimental spectra for the three
      halides, where the bulk structure of the ILs is dominated by H-bond interactions
      between the X- anion (X = Cl, Br and I) and the ortho protons of the pyridinium
      ring (a structural arrangement not too different from the solid-state structure
      of pyridinium halides). In contrast, when the H-bond is weak, as in the Br3-
      case, a number of supramolecular arrangements exist in solution and the simple
      DFT calculations of a few selected cases cannot exhaustively explore the complete
      energy landscape. Moreover, the dynamic effects due to thermal motion, evaluated
      by ADMP MD simulations of the chloride salt, appear to be not very significant.

PMID- 29645034
TI  - Intermolecular interactions between sigma- and pi-holes of
      bromopentafluorobenzene and pyridine: computational and experimental
      investigations.
AB  - The characters of sigma- and pi-holes of bromopentafluorobenzene (C6F5Br) enable
      it to interact with an electron-rich atom or group like pyridine which possesses
      an electron lone-pair N atom and a pi ring. Theoretical studies of intermolecular
      interactions between C6F5Br and C5H5N have been carried out at the M06-2X/aug-cc
      pVDZ level without and with the counterpoise method, together with single point
      calculations at M06-2X/TZVP, wB97-XD/aug-cc-pVDZ and CCSD(T)/aug-cc-pVDZ levels.
      The sigma- and pi-holes of C6F5Br exhibiting positive electrostatic potentials
      make these sites favorably interact with the N atom and the pi ring of C5H5N with
      negative electrostatic potentials, leading to five different dimers connected by
      a sigma-holen bond, a sigma-holepi bond or a pi-holepi bond. Their geometrical
      structures, characteristics, nature and spectroscopy behaviors were
      systematically investigated. EDA analyses reveal that the driving forces in these
      dimers are different. NCI, QTAIM and NBO analyses confirm the existence of
      intermolecular interactions formed via sigma- and pi-holes of C6F5Br and the N
      atom and the pi ring of C5H5N. The experimental IR and Raman spectra gave us
      important information about the formation of molecular complexes between C6F5Br
      and C5H5N. We expect that the results could provide valuable insights into the
      investigation of intermolecular interactions involving sigma- and pi-holes.

PMID- 29645035
TI  - Electron-driven spin diffusion supports crossing the diffusion barrier in MAS
      DNP.
AB  - Dynamic nuclear polarization (DNP) can be applied to enhance the sensitivity of
      solid-state NMR experiments by several orders of magnitude due to microwave
      driven transfer of spin polarization from unpaired electrons to nuclei. While the
      underlying quantum mechanical aspects are sufficiently well understood on a
      microscopic level, the exact description of the large-scale spin dynamics,
      usually involving hundreds to thousands of nuclear spins per electron, is still
      lacking consensus. Generally, it is assumed that nuclear hyperpolarization can
      only be observed on nuclei which do not experience strong influence of the
      unpaired electrons and thus being significantly removed from the paramagnetic
      polarizing agents. At the same time, sufficiently strong hyperfine interaction is
      required for DNP transfer. Therefore, efficient nuclear spin diffusion from the
      strongly-interacting nuclei to the NMR-observable bulk is considered to be
      essential for efficient nuclear hyperpolarization. Based on experimental results
      obtained on the endohedral fullerene N@C60 as a polarizing agent sparsely diluted
      in C60, we discuss the effect of the spin-diffusion barrier. We introduce
      electron-driven spin diffusion (EDSD) as a novel mechanism for nuclear
      polarization transfer in the proximity of an electron spin which is particularly
      relevant under magic-angle spinning (MAS) DNP conditions.

PMID- 29645036
TI  - The control of stereochemistry by the pentafluorosulfanyl group.
AB  - The influence of pentafluorosulfanylation on biological activity has been
      revealed in numerous comparative studies of biologically active compounds, but
      considerably less is known about the influence of pentafluorosulfanylation on
      reactivity. Among the distinctive properties of the pentafluorosulfanyl group is
      the profound dipole moment that results from introduction of this substituent. It
      has been shown that dipolar effects coupled with the steric demand of the SF5
      group may be employed to influence the stereochemistry of reactions, especially
      those processes with significant charge separation in the transition state. The
      Staudinger ketene-imine cycloaddition reaction is an ideal platform for
      investigation of dipolar control of diastereoselectivity by the
      pentafluorosulfanyl group.

PMID- 29645037
TI  - Stability of the zwitterionic liquid butyl-methyl-imidazol-2-ylidene borane.
AB  - Modification of the C2 position of the standard 1-butyl-3-methyl imidazolium
      cation by a borohydride group leads to a zwitterionic liquid (ZIL). The resulting
      imidazol-2-ylidene borane ZIL is liquid at room temperature. Dynamic viscosity as
      well as thermal and electrochemical stability are investigated. Thermal
      decomposition follows a similar pathway as in comparable imidazolium ionic
      liquids. The surprisingly low viscosity and good reductive stability make it a
      promising candidate for electrochemical applications.

PMID- 29645038
TI  - Pressure-induced anomalies and structural instability in compressed beta-Sb2O3.
AB  - Here, we report a high-pressure study of orthorhombic structured beta-Sb2O3
      (valentinite) by the combination of synchrotron in situ X-ray diffraction and
      first-principles theoretical calculations at pressures up to 40.5 GPa. Our
      results reveal that the metastable beta-Sb2O3 undergoes an isostructural phase
      transition at high pressure, yielding a distorted beta phase at 7-15 GPa through
      symmetry breaking and structural distortion as inferred from our XRD analyses and
      DFT theoretical calculations where pressure-induced elasticity softening is
      observed at pressures of 7-15 GPa. At pressures higher than 15 GPa, a new high
      pressure monoclinic phase is discovered from the current synchrotron X-ray
      diffraction data. Upon further compression up to ~33 GPa, the monoclinic Sb2O3
      starts to lose its long-range order and forms an amorphous component coexisting
      with the monoclinic one. To further explore the structural instability and
      understand the origin of pressure-induced phase transitions in beta-Sb2O3 upon
      compression, we have performed first-principles calculations to track the
      evolution of its phonon velocities, density of states and phonon dispersion
      curves under high pressure. Our results may play an important role in determining
      the local structures as well as their structural relationship among sesquioxides.

PMID- 29645039
TI  - The synergetic effects of Ti3C2 MXene and Pt as co-catalysts for highly efficient
      photocatalytic hydrogen evolution over g-C3N4.
AB  - Co-catalyst loading provides an effective way to enhance the efficiency of
      photocatalysts for solar hydrogen production. From a sustainability point of
      view, it has immense scientific and technological values to explore more
      efficient co-catalytic systems by using multi-cocatalysts, because of potential
      synergetic effects between different components. Herein, the feasibility of using
      Ti3C2 MXene nanoparticles and Pt nanoclusters as dual co-catalysts to enhance the
      photoactivity of g-C3N4 for H2 production was investigated. Due to the improved
      electrical conductivity and increased reactive sites for photoreduction
      reactions, Ti3C2 and Pt co-modified photocatalysts exhibited a high
      photocatalytic hydrogen production activity of 5.1 mmol h-1 g-1. Compared to g
      C3N4/Ti3C2 and g-C3N4/Pt, the 3- and 5-fold increased photoactivity demonstrated
      great potential of Ti3C2 MXene nanoparticles to construct high-performance
      photocatalysts. The synergetic effects between Ti3C2 and Pt were fundamentally
      investigated, indicating that the specific transfer of electrons not only
      contributed to the inhibited recombination of charge carriers but also resulted
      in good stability of heterostructured photocatalysts. Our results have
      demonstrated an approach worthy for the design and fabrication of high-efficiency
      heterostructures with superior photoactivity for hydrogen energy production.

PMID- 29645040
TI  - Computational studies of micellar and nanoparticle nanomedicines.
AB  - Nanomedicines are typically formed by nanocarriers which can deliver in a
      targeted manner drugs poorly soluble in blood, increase their therapeutic
      activities, and reduce their side effects. Many tested nanomedicines are formed
      by lipids, polymers, and other amphiphilic molecules isolated or self-assembled
      into various complexes and micelles, functionalized nanoparticles, and other bio
      compatible composite materials. Here, we show how atomistic molecular dynamics
      simulations can be used to characterize and optimize the structure, stability,
      and activity of selected nanomedicines. We discuss modeling of nanomedicines
      based on micelles, which can deliver selected therapeutic agents, and
      nanoparticles designed to act like large drugs. We show how to model
      nanomedicines interacting with lipid membranes, viruses, and amyloid fibrils.

PMID- 29645041
TI  - A novel monodisperse SiO2@C-dot for the rapid and facile identification of latent
      fingermarks using self-quenching resistant solid-state fluorescence.
AB  - Solid powder fluorescence shows great potential for application in medicine,
      biology, and engineering, especially in the identification of latent fingermarks
      in forensic science. However, conventional developing methods suffer from some
      drawbacks, such as low contrast, low sensitivity, low selectivity, and high
      toxicity. To conquer these challenges, novel SiO2@C-dot microspheres were
      prepared via a facile one-pot hydrothermal method by using citric acid as a
      carbon source and aminosilane as a nitrogen source. Interestingly, the results
      showed that the resultant powders possess good monodispersity, high fluorescence
      emission, and resistance to self-quenching. Additionally, the mechanism for the
      solid-state fluorescence of SiO2@C-dot compounds was also investigated. More
      importantly, the fingermarks on various surfaces, including transparent glasses,
      ceramic tiles, transparent plastics, aluminum alloys, plastic cards, painted
      woods, artificial leathers, and Chinese paper money, developed by the powders
      have indicated well-defined papillary ridges under a 365 nm UV lamp. The novel
      strategy of using monodisperse SiO2@C-dot microspheres as a fluorescent label for
      developing latent fingermarks showed greater advantages compared to conventional
      methods, which was also demonstrated using the automatic fingerprint
      identification system. It is simple, rapid, low-cost, nontoxic, and effective,
      and is expected to be a promising alternative for the development of latent
      fingerprints in forensic science.

PMID- 29645043
TI  - Evidence for anion-binding of all-cis hexafluorocyclohexane in solution and solid
      state.
AB  - We report a solution NMR and X-ray crystallographic study on the anion affinity
      of all-cis 1,2,3,4,5,6-hexafluorocyclohexane, which has only recently become
      synthetically accessible. Our results suggest that the interaction exhibits
      preferential 1 : 1 stoichiometry, while its strength is only moderate (e.g. Ka =
      400 M-1 in acetone for Cl-) and depends mainly on the size of the anion and the
      dielectric constant of the solvent.

PMID- 29645042
TI  - Tailored photocleavable peptides: fragmentation and neutralization pathways in
      high vacuum.
AB  - Photocleavable tags (PCTs) have the potential for excellent spatio-temporal
      control over the release of subunits of complex molecules. Here, we show that
      electrosprayed oligopeptides, functionalized by a tailored ortho-nitroarylether
      can undergo site-specific photo-activated cleavage under UV irradiation (266 nm)
      in high vacuum. The comparison of UV photodissociation (UVPD) and collision
      induced dissociation (CID) points to the thermal nature of the cleavage
      mechanism, a picture corroborated by the temperature dependence of the process.
      Two competing photodissociation pathways can be identified. In one case a
      phenolate anion is separated from a neutral zwitterion. In the other case a
      neutral phenol derivative leaves a negatively charged peptide behind. To
      understand the factors favoring one channel over the other, we investigate the
      influence of the peptide length, the nature of the phenolic group and the
      position of the nitro-group (ortho vs. para). The observed gas phase cleavage of
      a para-nitro benzylic ether markedly differs from the established behavior in
      solution.

PMID- 29645044
TI  - Metal-free iodine(iii)-promoted synthesis of 2,5-diaryloxazoles.
AB  - A nonmetal-catalyzed oxidative cyclization to achieve 2,5-disubstituted oxazoles
      from inexpensive and readily available substituted chalcone,
      (diacetoxyiodo)benzene (PIDA) and ammonium acetate (NH4OAc) at room temperature
      is described. The reaction forms a variety of 2,5-diaryloxazoles in good to
      excellent yields with broad substrate scope under mild conditions without the
      requirement of ligands and additional bases.

PMID- 29645045
TI  - O-Substituted hydroxyl amine reagents: an overview of recent synthetic advances.
AB  - Reagents derived from hydroxylamines such as 2,4-dinitrophenylhydroxylamine
      (DPH), O-(diphenylphosphinyl)hydroxylamine (DPPH), hydroxylamine-O-sulfonic acid
      (HOSA) and other related reagents in which oxygen is substituted with good
      leaving groups recently showed remarkable potential as electrophilic aminating
      agents and as a source of the amino group. They facilitate stereo- and
      regioselective C-N, N-N, O-N, and S-N bond-formation reactions and intra
      molecular cyclizations without the requirement of expensive metal catalysts. In
      this review we have discussed the important transformations achieved with these
      reagents.

PMID- 29645046
TI  - Oxygen, sulfur and selenium terminated single-walled heterocyclic carbon
      nanobelts (SWHNBs) as potential 3D organic semiconductors.
AB  - Carbon nanomaterials such as polyaromatic hydrocarbons (PAHs), graphene,
      fullerenes and nanotubes are on the frontline of materials research due to their
      excellent physical properties, which in recent years, have started to compete
      with conventional inorganic materials in charge transfer based applications.
      Recently, a variety of new structures such as single-walled carbon nanobelts
      (SWCNBs) have been conceived, however, to date only one 'all-phenyl' example has
      been synthesised, due to problems with their stability and the challenging
      synthetic methodologies required. This study introduces a new class of phenacene
      based SWCNBs and their chalcogenide derivatives, forming the new sub-class of
      single-walled heterocyclic carbon nanobelts (SWHNBs) which are expected to be
      both more stable and easier to synthesise than the all carbon analogues.
      Subsequent theoretical examination of the structure-property relationships found
      that unlike the small-molecule acene homologues (tetracene, pentacene etc.) which
      become more reactive with addition of oxygen, an increase in the molecular size
      of the SWCNBs actually stabilises the HOMO energy level, in correlation with the
      increasingly negative nuclear independent chemical shift (NICS) calculations of
      their cylindrical aromaticities. The FMO energies of the phenacene SWCNBs are
      similar to that of the nanobelt reported by Itami and co-workers, but those of
      the SWHNBs are deeper and thus more stable. The sulfur derivative of one SWHNB
      was found to give hole-charge transfer mobilities as high as 1.12 cm2 V-1 s-1,
      which is three orders of magnitude larger than the corresponding unsubstituted
      SWCNB (3 * 10-3 cm2 V-1 s-1). These findings suggest the candidates are air
      stable and potentially high-performing organic semiconductors for organic thin
      film transistor (OTFT) devices, while the structure-property relationships
      uncovered here will aid the design and synthesis of future three-dimensional
      organic nanomaterials.

PMID- 29645047
TI  - Boolean-chemotaxis of logibots deciphering the motions of self-propelling
      microorganisms.
AB  - We demonstrate the feasibility of a self-propelling mushroom motor, namely a
      'logibot', as a functional unit for the construction of a host of optimized
      binary logic gates. Emulating the chemokinesis of unicellular prokaryotes or
      eukaryotes, the logibots made stimuli responsive conditional movements at varied
      speeds towards a pair of acid-alkali triggers. A series of integrative logic
      operations and cascaded logic circuits, namely, AND, NAND, NOT, OR, NOR, and
      NIMPLY, have been constructed employing the decisive chemotactic migrations of
      the logibot in the presence of the pH gradient established by the sole or coupled
      effects of acid (HCl-catalase) and alkali (NaOH) drips inside a peroxide bath.
      The imposed acid and/or alkali triggers across the logibots were realized as
      inputs while the logic gates were functionally reconfigured to several
      operational modes by varying the pH of the acid-alkali inputs. The self
      propelling logibot could rapidly sense the external stimuli, decide, and act on
      the basis of intensities of the pH triggers. The impulsive responses of the
      logibots towards and away from the external acid-alkali stimuli were interpreted
      as the potential outputs of the logic gates. The external stimuli responsive self
      propulsion of the logibots following different logic gates and circuits can not
      only be an eco-friendly alternative to the silicon-based computing operations but
      also be a promising strategy for the development of intelligent pH-responsive
      drug delivery devices.

PMID- 29645048
TI  - A 2',2'-disulfide-bridged dinucleotide conformationally locks RNA hairpins.
AB  - The synthesis and the impact of a disulfide bridge between 2'-O-positions of two
      adjacent nucleotides in an RNA duplex and in the loop of RNA hairpins are
      reported. The incorporation of this 2',2'-disulfide (S-S) bridge enabled thermal
      and enzymatic stabilization of the hairpin depending on its position in the loop.
      The influence of the disulfide bridge on RNA folding was studied at the HIV
      Dimerization Initiation Site (DIS) as an RNA sequence model. We have shown that
      this S-S bridge locked the hairpin form, whereas the extended duplex form was
      generated after the reduction of the disulfide bond in the presence of tris(2
      carboxyethyl)phosphine or glutathione. Thus, the S-S bridge can be useful for
      understanding RNA folding; an RNA molecular beacon locked by an S-S bridge was
      also investigated as a sensor for the detection of glutathione.

PMID- 29645049
TI  - The inhibitory effect of Manuka honey on human colon cancer HCT-116 and LoVo cell
      growth. Part 1: the suppression of cell proliferation, promotion of apoptosis and
      arrest of the cell cycle.
AB  - Numerous investigations have been made on plant phenolic compounds and cancer
      prevention in recent decades. Manuka honey (MH) represents a good source of
      phenolic compounds such as luteolin, kaempferol, quercetin, gallic acid and
      syringic acid. The aim of this work was to evaluate the chemopreventive effects
      of MH on human colon cancer HCT-116 and LoVo cells. Both cells were exposed to
      different concentrations of MH (0-20 mg mL-1 for HCT-116 cells and 0-50 mg mL-1
      for LoVo cells) for 48 h to measure apoptosis and cell cycle arrest as well as
      apoptosis and cell cycle regulatory gene and protein expression. MH exhibited
      profound inhibitory effects on cellular growth by reducing the proliferation
      ability, inducing apoptosis and arresting the cell cycle in a dose-dependent
      manner. Interestingly, MH treatment in non-malignant cells did not exert any
      significant toxicity at similar concentrations. The apoptosis event was
      associated with the increasing expression of p53, cleaved-PARP and caspase-3 and
      with the activation of both intrinsic (caspase-9) and extrinsic (caspase-8)
      apoptotic pathways. MH induced cell cycle arrest in the S phase in HCT-116 cells,
      and simultaneously, in LoVo cells, it occurred in the G2/M phase through the
      modulation of cell cycle regulator genes (cyclin D1, cyclin E, CDK2, CDK4, p21,
      p27 and Rb). The expression of p-Akt was suppressed while the expression of p
      p38MAPK, p-Erk1/2 and endoplasmic stress markers (ATF6 and XBP1) was increased
      for apoptosis induction. Overall, these findings indicate that MH could be a
      promising preventive or curative food therapy for colon cancer.

PMID- 29645050
TI  - Hierarchical whisker-on-sheet NiCoP with adjustable surface structure for
      efficient hydrogen evolution reaction.
AB  - We have reported the synthesis of hierarchical whisker-on-sheet (HWS) NiCoP
      anchored on Ni foam with adjustable surface structure for efficient hydrogen
      evolution reaction (HER). The HWS NiCoP was obtained by controllable
      phosphidation of HWS Ni-Co-carbonates hydroxide precursor grown on Ni foam (NF).
      The experimental parameters were optimally tuned to understand the formation
      process of the precursor and to regulate the microstructure of the materials. The
      test results indicated that the HWS NiCoP/NF can produce a current density of 10
      mA cm-2 (eta10) at a low overpotential of 59 mV and a current density of 100 mA
      cm-2 (eta100) at an overpotential of 220 mV for HER. Notably, upon surface
      activation with KOH, the HER performance of HWS NiCoP/NF could be dramatically
      enhanced with eta10 and eta100 values of 42 mV and 141 mV, respectively. The HWS
      NiCoP/NF showed a superior performance to NiCoP displaying other morphologies
      (sheets and wires etc.) The good performance of HWS NiCoP/NF should be attributed
      to their special whisker-on-sheet structures that are favourable for effective
      contact with the electrolyte. Also, hydrated metals can be formed on surface
      after the alkali treatment step, which is beneficial to moderate the bonding to
      hydrogen and thus, improve the HER activity. The present study will be indicative
      toward the construction of highly-efficient HER catalysts by regulating the
      structure of the materials.

PMID- 29645051
TI  - Direct synthesis of alkenyl iodides via indium-catalyzed iodoalkylation of
      alkynes with alcohols and aqueous HI.
AB  - A convenient and efficient indium-catalyzed approach to synthesize alkenyl
      iodides has been developed through direct iodoalkylation of alkynes with alcohols
      and aqueous HI under mild conditions. This catalytic protocol offers an
      attractive approach for the synthesis of a diverse range of alkenyl iodides in
      good to excellent yields.

PMID- 29645052
TI  - Sulfonated carbon-encapsulated iron nanoparticles as an efficient magnetic
      nanocatalyst for highly selective synthesis of benzimidazoles.
AB  - Surface functionalized carbon-encapsulated iron nanoparticles (CEINs) were found
      to be a magnetic nanocatalyst for the efficient and highly selective synthesis of
      benzimidazoles. CEINs were covalently decorated with carboxyl or sulfonyl groups
      and their catalytic activity was examined. Carboxyl-modified CEINs were obtained
      via the radical or oxidative treatment, whilst the sulfonated CEINs were obtained
      using the one-step diazotization approach with sulfanilic acid and isoamyl
      nitrite. The content of surface acidic groups varied between the obtained
      materials and was found to be the highest for sulfonyl-modified CEINs. CEINs
      functionalized with sulfonyl groups were the most efficient and the most
      selective nanocatalyst for the synthesis of benzimidazoles. Various
      benzimidazoles were obtained in very high yields (92.5-97.0%). Both metallocene,
      aliphatic, heterocyclic and aromatic aldehydes substituted with different
      functional groups were subjected to the synthesis process. The reaction proceeded
      in a short time, which varied from 25 min to 65 min depending on the aldehyde
      used. Additionally, the mechanism of the studied catalytic condensation by
      applying sulfonated CEINs as the catalyst was discussed. Importantly, the
      developed magnetic nanocatalysts could be easily separated from the reaction
      mixture using a permanent magnet. The nanocatalysts can be used up to six
      reaction cycles without any significant loss of their catalytic activity. This
      work opens up new ways for very efficient and simple synthesis of benzimidazoles 
      an important class of organic compounds for various biomedical applications.

PMID- 29645053
TI  - Morphological control of lanthanide ferrocyanides and their highly efficient
      catalytic degradation performance toward organic dyes under dark ambient
      conditions.
AB  - KCe[FeII(CN)6].4H2O (CePBA), a Prussian blue analogue, was successfully
      synthesized with various morphologies and different sizes. CePBA, when used as a
      heterogeneous catalyst, can rapidly and completely degrade a large number of
      methylene blue molecules in 30 seconds: 14.5 mg of MB (for each 5 mg of
      catalyst). The CePBA catalyst is reusable. These are very important parameters
      for practical applications.

PMID- 29645054
TI  - Synthesis and non-conventional structure of square-planar Pd(ii) and Pt(ii)
      complexes with an N,C,N-chelated stibinidene ligand.
AB  - The N,C,N-chelated stibinidene, ArSb (Ar = C6H3-2,6-(CH[double bond, length as m
      dash]NtBu)2), reacts with Pt(ii) compounds [PtCl2L2] resulting in the formation
      of 1 : 1 complexes, cis-[PtCl2L(ArSb)] (L = Me2S (1), dmso (2)). In contrast,
      attempts to synthesize similar Pd(ii) complexes failed, resulting only in the
      formation of elemental palladium. To increase the stability of the ArSb
      complexes, in particular those containing Pd(ii), the simple auxiliary ligands
      were replaced with C,N-chelating ones, which led to a set of four compounds of
      the type [RMCl(ArSb)], where R = C6H4-2-(CH2NMe2) or Fe(eta5-C5H4)(eta5-C5H3-2
      (CH2NMe2)) and M = Pd (3, 5) or Pt (4, 6). Compounds 1-6 were characterized by 1H
      and 13C{1H} NMR spectroscopy and single-crystal X-ray diffraction analysis, and
      in the case of ferrocene derivatives 5 and 6, also by cyclic voltammetry.
      Compounds 2-6 were shown to form rotamers in solution due to the side-on
      coordination of the ArSb ligand and a hindered rotation around the Sb-Pd(Pt)
      bond. This process was investigated by 1H-VT-NMR spectroscopy and by DFT
      computations.

PMID- 29645055
TI  - Cysteine-reactive probes and their use in chemical proteomics.
AB  - Proteomic profiling using bioorthogonal chemical probes that selectively react
      with certain amino acids is now a widely used method in life sciences to
      investigate enzymatic activities, study posttranslational modifications and
      discover novel covalent inhibitors. Over the past two decades, researchers have
      developed selective probes for several different amino acids, including lysine,
      serine, cysteine, threonine, tyrosine, aspartate and glutamate. Among these amino
      acids, cysteines are particularly interesting due to their highly diverse and
      complex biochemical role in our cells. In this feature article, we focus on the
      chemical probes and methods used to study cysteines in complex proteomes.

PMID- 29645056
TI  - Electrochemical Hg2+ detection at tannic acid-gold nanoparticle modified
      electrodes by square wave voltammetry.
AB  - We report the electrochemical sensing of Hg2+ based on tannic acid capped gold
      nanoparticle (AuNP@TA) complexes. At optimal conditions using square wave
      voltammetry, the presented analytical method exhibits a "measurable lower limit"
      of 100.0 fM. This limit is considerably below the permissible level of 30.0 nM
      for inorganic mercury in drinking water, specified by the World Health
      Organization (WHO). The effect of potentially interfering ions, such as Zn2+ and
      Al3+, was studied and results indicate an excellent selectivity for Hg2+. The
      transfer of the proposed strategy onto AuNP@TA modified screen-printed electrodes
      demonstrates its applicability to routine monitoring of Hg2+ in tap water.

PMID- 29645057
TI  - Driving dimethyl carbonate synthesis from CO2 and methanol and production of
      acetylene simultaneously using CaC2.
AB  - The synthesis of dimethyl carbonate (DMC) from CO2 and methanol is a very
      interesting reaction, but is thermodynamically limited. In this work, CaC2 was
      used to consume the water produced in the reaction to shift the reaction
      equilibrium, and C2H2 was produced at the same time. This is the first work on
      the combination of driving a thermodynamically unfavorable reaction and producing
      C2H2 using CaC2.

PMID- 29645058
TI  - Recent advances in nanoparticle-based lateral flow immunoassay as a point-of-care
      diagnostic tool for infectious agents and diseases.
AB  - Lateral flow immunoassay (LFIA) technology is a paper-based, point-of-care strip
      biosensor designed to detect a specific analyte in a given sample. This type of
      assay is now of great interest to researchers for its cost-effectiveness,
      simplicity, portability and rapidness of detection of analytes, including but not
      limited to areas such as agriculture, food, biomedicine and pathogen detection.
      Various nanoparticles (such as metal nanoparticles, carbon-based nanoparticles,
      quantum dots, lanthanides and up-converting phosphor) functionalized by an
      antibody to detect an analyte protein or molecular marker present in the surface
      of an infectious pathogen are used for in LFIAs. Herein, we review the principle
      of the assay and recent advancements made in terms of the different approaches
      and designs of the assay towards the detection of infectious agents and diseases.

PMID- 29645059
TI  - Diagnosis of thymic epithelial tumor subtypes by a quantitative proteomic
      approach.
AB  - The histological typing of thymic epithelial tumours (TETs) still remains a
      challenge for surgical pathologists, especially when encountering borderline
      cases mainly focused on spindle cell types (including type A, atypical type A
      (aA), AB, and B3). A systematic proteomics analysis of TETs was performed using
      isobaric tags for relative and absolute quantification (iTRAQ) labeling coupled
      with two-dimensional liquid chromatography-tandem mass spectrometry (2D-LC
      MS/MS). In total, 6479 and 6305 proteins were identified and quantified,
      respectively. After Gene Ontology (GO) annotation and Ingenuity Pathway Analysis
      (IPA), six differentially expressed proteins were validated by tissue microarray
      or multiple reaction monitoring (MRM) quantification. ABCE1 and CLIC2 are
      promising to be diagnostic candidate biomarkers in thymic carcinomas (TCs). CHD1L
      was up-regulated in type AB and type B thymomas compared with type A thymoma.
      Both CLIC2 and MAP7 were negatively detected in type B1 and B2 thymomas. SMAD4
      was overexpressed in type aA thymomas and TCs. CDC42 was significantly down
      regulated in type B2 thymomas compared with other subtypes. Six novel candidate
      biomarkers were found to be useful in differentiating subtypes of TETs. SMAD4 may
      play a specific role in tumorigenesis and the development of aA thymomas and
      thymic carcinomas.

PMID- 29645060
TI  - Self-assembly of model short triblock amphiphiles in dilute solution.
AB  - In this work, a molecular theory is used to study the self-assembly of short
      diblock and triblock amphiphiles, with head-tail and head-linker-tail structures,
      respectively. The theory was used to systematically explore the effects of the
      molecular architecture and the affinity of the solvent for the linker and tail
      blocks on the relative stability of the different nanostructures formed by the
      amphiphiles in dilute solution, which include spherical micelles, cylindrical
      fibers and planar lamellas. Moreover, the theory predicts that each of these
      nanostructures can adopt two different types of internal organization: (i) normal
      nanostructures with a core composed of tail segments and a corona composed of
      head segments, and (ii) nanostructures with a core formed by linker segments and
      a corona formed by tail and head segments. The theory predicts the occurrence of
      a transition from micelle to fiber to lamella when increasing the length of the
      tail or the linker blocks, which is in qualitative agreement with the geometric
      packing theory and with experiments in the literature. The theory also predicts a
      transition from micelle to fiber to lamella as the affinity of the solvent for
      the tail or linker block is decreased. This result is also in qualitative
      agreement with experiments in the literature but cannot be explained in terms of
      the geometric packing theory. The molecular theory provides an explanation for
      this result in terms of the competition between solvophobic attractions among
      segments in the core and steric repulsions between segments in the corona for the
      different types of self-assembled nanostructures.

PMID- 29645061
TI  - Palladium-catalyzed carbonylation of benzylic ammonium salts to amides and esters
      via C-N bond activation.
AB  - An efficient palladium-catalyzed carbonylation reaction of readily available
      quaternary ammonium salts with CO is reported for the first time to afford
      arylacetamides and arylacetic acid esters via benzylic C-N bond cleavage. This
      protocol features mild reaction conditions under atmospheric pressure of CO, a
      redox-neutral process without an additional oxidant, and a broad substrate scope
      for various kinds of amines, alcohols and phenols.

PMID- 29645062
TI  - Straightforward synthesis of enantiomerically pure 1,2,3-triazoles derived from
      amino esters.
AB  - A practical and straightforward approach that enables, for the first time, the
      synthesis of enantiomerically pure 1,4,5-trisubstituted, 1,5-disubstituted, and
      fused 1,2,3-triazole derivatives has been developed. The synthesis employs
      enantiomerically pure amino esters derived from amino acids and commercially
      available ketones under metal-free conditions.

PMID- 29645063
TI  - Realisation of small molecule libraries based on frameworks distantly related to
      natural products.
AB  - The availability of high-quality screening compounds is of paramount importance
      for the discovery of innovative new medicines. Natural product (NP) frameworks
      can inspire the design of productive compound libraries. Here, we describe the
      design and synthesis of four compound libraries based on scaffolds that have
      broad NP-like features, but that are only distantly related to specific NPs. The
      optimisation of syntheses of the scaffolds using [5 + 2] cycloaddition chemistry
      is detailed, together with methods to yield exemplar decorated screening
      compounds. In each case, a library was nominated for production, leading to a
      total of >2900 screening compounds that augmented the Joint European Compound
      Library of the European Lead Factory.

PMID- 29645064
TI  - Adiponectin expression in visceral adiposity is an important determinant of
      insulin resistance in morbid obesity.
AB  - INTRODUCTION: Visceral adiposity is associated with decreased serum adiponectin
      levels, peripheral resistance to insulin and an increased risk of cardio
      metabolic complications. However, the link between adiponectin expression in
      visceral adipose tissue (VAT), its serum levels and metabolic protection is
      controversial. The aim of this study was to investigate the relationship between
      the adiponectin gene expression in VAT and clinical and metabolic parameters in
      patients with severe obesity. MATERIAL AND METHODS: This is a cross-sectional
      study that included 51 severely obese patients (age 43.24+/-11.29 years, BMI
      45.13+/-8.67 kg/m2), extensively evaluated clinically and biologically (metabolic
      tests, serum adiponectin measurements, HOMA-IR) before bariatric surgery. Omental
      adipose tissue was sampled during the intervention and the relative
      quantification of adiponectin gene expression was performed by real-time PCR,
      using beta-actin as reference gene. RESULTS: Adiponectin mRNA in VAT was
      significantly higher in obese insulin-sensitive patients than in the rest of
      obese patients (p < 0.05) and negatively correlated with HOMA-IR (r =-0.354,
      p=0.016) and uric acid (r =-0.304, p=0.045). After adjustment for gender, TG/HDL
      ratio and uric acid, adiponectin expresion (beta= -0.439, p=0.001), waist
      circumference (beta=0.467, p=0.001) and serum adiponectin (beta =-0.339, p=0.011)
      remained significantly associated with HOMA-IR, together explaining more than 50%
      of its variation. CONCLUSIONS: In severely obese patients, adiponectin gene
      expression in VAT is negatively correlated with serum levels of uric acid and is
      an independent determinant, together with anthropometric parameters of visceral
      obesity and serum adiponectin levels, of insulin resistance.

PMID- 29645065
TI  - 131-I MIBG therapy of malignant pheochromocytoma and paraganglioma tumours - a
      single-centre study.
AB  - INTRODUCTION: Pheochromocytomas and paragangliomas are rare tumors deriving from
      chromaffin cells of adrenal medulla or paraganglia. They are usually benign but
      10-35% of them present malignant behavior. The aim of the study was to evaluate
      the efficacy and safety of 131-I MIBG therapy in malignant pheochromocytoma
      /paraganglioma patients (MPPGL). MATERIAL AND METHODS: 18 patients (7 women and
      11 men) were included in this study. Between 2002 and 2016 they underwent 131-I
      MIBG therapy because of MPPGL and their medical data were analyzed
      retrospectively. Clinical indications for the treatment included progressive
      disease or massive tissue involvement independently from disease progression.
      Tumor response for the first time was assessed 3 months after the last treatment
      according to Response Evaluation Criteria in Solid Tumors criteria and by 131-I
      MIBG scans. RESULTS: The mean single dose used was 7.25 GBq (196 mCi) and mean
      cumulative dose 33.08 GBq ( 894 mCi). In 2 (11%) patients complete tumor response
      was achieved. In 1 (6%) patient partial response was obtained. In 13 (72%)
      patients stable disease was observed. In 2 (11%) patients progression was
      diagnosed three months after treatment discontinuation. In the whole studied
      group the progression free survival time was 85 months and overall 5-year
      survival was 87%. CONCLUSIONS: Radionuclide treatment with use of 131-I MIBG may
      be effective form of palliative treatment for patients with inoperative neoplasm
      spread, progressive disease or patients requiring alleviation of symptoms. < p >
      < /p >.

PMID- 29645066
TI  - Intellectual performance of children of mothers with an untreated thyroid
      disorder in the first trimester of pregnancy.
AB  - INTRODUCTION: The focus of the present study was the importance of the mother's
      thyroid function for foetal development in the first trimester, when the baby is
      totally dependent on the mother for thyroid hormones. MATERIAL AND METHODS: The
      study consisted in testing the intellectual performance of children with both
      euthyroid and thyroid-dysfunction mothers. The experimental group comprised 60
      children of mothers with an untreated thyroid disorder in the first trimester of
      their pregnancy (TSH>=3.5 and/or TPO-Ab>=20). The control group contained 132
      children whose mothers showed no symptoms of a thyroid disorder either before or
      during pregnancy/postpartum. Both groups of children were administered the WISC
      III, whereby the intellectual performance of the experimental-group children was
      compared with that of the control-group children. The comparison included the
      percentage of children with IQ<= 85 and SLD and/or ADD risks. Our research is a
      follow-up to a blanket thyroid screening of 1 649 pregnant women conducted during
      2004-2006 in the region around Havlickuv Brod. RESULTS: The research found no
      significant difference between the two groups of children with respect to their
      intellectual abilities, either regarding their overall IQ (p=0.67), verbal IQ
      (p=0.81), performance IQ (p=0.41), or the individual scores (ISP: p=0.85; IPU:
      p=0.54, IKO: p=0.57; IRZ: p=0.13), nor did the experimental group show a
      significantly higher occurrence of children with IQ<=85 than the control group
      (p=0.66). However, the experimental group did exhibit a statistically significant
      increase in the percentage of children with a suspected SLD or clinically
      significant attention issues (p =0.05). CONCLUSION: Untreated thyroid disorders
      in the first trimester of pregnancy can increase the risk of the child developing
      attention or learning issues. < p > < /p >.

PMID- 29645067
TI  - [New drugs for the treatment of multiple sclerosis].

PMID- 29645068
TI  - [Frequency, semiology and prognosis of benign infantile epilepsy].
AB  - INTRODUCTION: Benign infantile epilepsy is an epileptic syndrome of infancy.
      Until now, only a small number of case-series have been published. AIM: To study
      the frequency, semiology and prognosis of benign infantile epilepsy. PATIENTS AND
      METHODS: The 827 patients with one or more epileptic seizures seen at our
      hospital between 1 June 1994 and 1 March 2011 were included and prospectively
      followed. A diagnosis of benign infantile epilepsy was made in patients that
      fulfilled the following criteria at six month of evolution: one or more focal
      and/or generalised seizures, onset before 24 months, no neurological deficit and
      normal neuroimaging and interictal EEG. RESULTS: 77 cases (9%) met the diagnostic
      criteria. Semiology of the seizures was similar to that of other focal seizures
      in children under 24 months. 25% of the patients remained as isolated seizures.
      Among those with two or more seizures, the probability of achieving a 3 year
      initial remission without antiepileptic treatment was 86%. In the subgroup of
      patients with focal seizures without family history the probability was 74% and
      in five cases a global developmental delay/intellectual disability was detected
      thereafter. CONCLUSIONS: Benign infantile epilepsy is a frequent epileptic
      syndrome. Semiology of seizures is not useful to characterize the syndrome. A
      diagnosis of benign infantile epilepsy at six month of evolution implies a
      reasonably good prognosis, but possibly not as good as for other self-limited
      epilepsies of infancy.

PMID- 29645069
TI  - [Childhood ischemic cerebrovascular disease in a paediatric emergency service: a
      descriptive study].
AB  - AIM: To describe the clinical presentation, risk factors and complementary tests
      in patients of our paediatric emergency service with a final diagnosis of
      ischemic stroke. PATIENTS AND METHODS: Retrospective, analytical and
      observational study, performed in a Paediatric Emergency Service of a tertiary
      level hospital. We included patients aged 1 month to 14 years during a 12-years
      period with a final diagnosis of ischemic cerebrovascular disease (CVD). We
      analyzed personal history, symptomatology and initial complementary tests.
      RESULTS: Twelve patients were included, 66% males, with a median age of 77
      months. 42% had remarkable history. The most frequent clinical manifestation was
      motor disorder (75%). 42% were diagnosed in the first 24 hours, noticing an
      earlier diagnosis after the introduction of a multidisciplinary protocol about
      CVD. CT was performed in all patients, except in two cases in whom MRI was
      performed. 50% of the CTs were initially normal. In the etiological study
      developed lately, only 42% of the patients had risk factors. 91% had some kind of
      sequel. CONCLUSIONS: CVD is uncommon in pediatrics, but with a high
      morbimortality, so it is important to make an early diagnosis. Clinical and
      personal history are fundamental, nevertheless, we mainly deal with a previously
      healthy child without known risk factors at the time of the first evaluation. In
      case of clinical suspicion of stroke, a normal initial CT does not rule out a
      CVD, so other additional tests, such as MRI, are necessary.

PMID- 29645070
TI  - [Isolated girdle weakness: expansion of the phenotypic spectrum of the MERRF
      8344A>G mutation of mitochondrial DNA].
AB  - INTRODUCTION: The differential diagnosis of diseases that are accompanied by
      adult-onset girdle weakness is broad and includes motor neurone, neuromuscular
      junction or muscular diseases. The 8344A>G mutation of the MTTK gene of
      mitochondrial DNA usually presents with involvement of multiple organs associated
      (or not) with girdle weakness. To date no cases of isolated girdle weakness have
      been reported as the presenting symptom of this mutation. CASE REPORT: A 57-year
      old male, with a four-year history of isolated clinical signs of progressive
      girdle weakness. He is the brother of a 59-year-old woman with the same clinical
      features. Muscular biopsy played a decisive role in the diagnosis and was
      characteristic of mitochondrial myopathy. The genetic analysis revealed the
      8344A>G mutation of the MTTK gene of mitochondrial DNA. CONCLUSIONS: The 8344A>G
      mutation of mitochondrial DNA can be associated with clinical signs and symptoms
      of adult-onset girdle weakness, and must therefore be included as part of its
      differential diagnosis.

PMID- 29645071
TI  - Daclizumab in multiple sclerosis.
AB  - INTRODUCTION: Daclizumab is a monoclonal antibody directed against the CD25
      subunit of the interleukin-2 receptor, investigated as a disease-modifying
      therapy in relapsing-remitting multiple sclerosis. The present review addresses
      how the drug was developed, the known mechanism of action of the drug and the up
      to-date data of efficacy and safety. DEVELOPMENT: Daclizumab has shown
      superiority in prevention of relapses against placebo and low-dose interferon
      beta-1a at a level that puts it on par with the rest of current first-line drugs.
      The effect on the progression of the disease and on neurodegeneration parameters,
      however, is not clear. On the other hand, it presents safety problems (mainly
      risk of autoimmunity phenomena including fulminant hepatopathy and encephalitis)
      that have supposed eventually its withdrawn from marketing. Daclizumab introduces
      a new mechanism of action through the blocking of a key interleukin in immune
      regulation and its effect on a population of cells with regulatory ability, such
      as the NK CD56(bright) cells. CONCLUSIONS: Daclizumab has shown efficacy in
      slowing the inflammatory process of multiple sclerosis, although the appearance
      of potentially serious side effects has not allowed its use to significantly
      impact current clinical practice. The development of new drugs in multiple
      sclerosis must be contingent on maintaining or improving the risk-benefit profile
      with respect to those already in use.

PMID- 29645072
TI  - [XIX Reunion Anual de la Sociedad Extremena de Neurologia. Communications].

PMID- 29645073
TI  - [Optochiasmatic tuberculomas as a paradoxical reaction to treatment for meningeal
      tuberculosis].

PMID- 29645074
TI  - [Microcephalies and Zika virus].

PMID- 29645075
TI  - Results of second salvage therapy in 673 adults with acute myelogenous leukemia
      treated at a single institution since 2000.
AB  - BACKGROUND: The prognosis is poor for patients who have relapsed-refractory acute
      myelogenous leukemia (AML). Most published reports analyzed results from
      therapies in first-salvage AML or in studies that were conducted before 2000.
      Several novel agents and strategies are being tested for potential approval as
      treatment for patients with relapsed-refractory AML in second salvage. Therefore,
      it is important to establish the historic results of anti-AML therapies in this
      setting in the modern era. The objective of the current study was to analyze the
      results from second salvage therapies in patients with AML since 2000 with regard
      to response and survival. METHODS: In total, 673 patients who received second
      salvage therapies for AML since 2000 were analyzed. Their median age was 60 years
      (range, 18-89 years). Salvage therapy consisted of cytarabine-based regimens in
      267 patients, noncytarabine combinations in 37, hypomethylating agent-based
      regimens in 136, and phase 1 and 2 single agents in 233. RESULTS: Eighty-six of
      the 673 patients (13%) achieved a complete response (CR) or a CR with low
      platelet count (CRp). The median duration of CR-CRp was 7.2 months. The median
      survival was 4.4 months (95% confidence interval, 4.0-4.8 months), and the 1-year
      survival rate was 16% (95% confidence interval, 14%-19%). Multivariate analysis
      identified the following as independent adverse factors for achievement of CR
      CRp: platelets < 50 * 109 /L (P < .001), complex karyotype with >=3 chromosomal
      abnormalities (P = .02), regimens that did not include cytarabine or
      hypomethylating agents (P = .014), and no prior CR lasting >=12 months with
      frontline or salvage 1 therapies (P < .001). The independent adverse factors
      associated with worse survival were age >=60 years (P = .01), platelets < 50 *
      109 /L (P = .02), peripheral blasts >= 20% (P = .03), albumin <= 3 g/dL (P =
      .04), and complex karyotype (P = .003). The authors also applied and validated,
      in the current population, the 2 multivariate-derived prognostic models for CR
      and survival developed in their previous study of 594 patients who received
      treatment for second salvage AML from the previous 2 decades. CONCLUSIONS: This
      large-scale analysis establishes the modern historic results of second salvage
      therapy in AML and validates the prognostic models associated with outcome. These
      data could be used to analyze the differential benefits of current or future
      investigational strategies under evaluation in this setting and for the purpose
      of potential approval of new agents in the United States and the world. Cancer
      2018;124:2534-40. (c) 2018 American Cancer Society.

PMID- 29645076
TI  - The role of external beam radiotherapy in the treatment of hepatocellular cancer.
AB  - Hepatocellular carcinoma (HCC) is increasing in incidence and mortality. Although
      the prognosis remains poor, long-term survival has improved from 3% in 1970 to an
      18% 5-year survival rate today. This is likely because of the introduction of
      well tolerated, oral antiviral therapies for hepatitis C. Curative options for
      patients with HCC are often limited by underlying liver dysfunction/cirrhosis and
      medical comorbidities. Less than one-third of patients are candidates for
      surgery, which is the current gold standard for cure. Nonsurgical treatments
      include embolotherapies, percutaneous ablation, and ablative radiation.
      Technological advances in radiation delivery in the past several decades now
      allow for safe and effective ablative doses to the liver. Conformal techniques
      allow for both dose escalation to target volumes and normal tissue sparing.
      Multiple retrospective and prospective studies have demonstrated that
      hypofractionated image-guided radiation therapy, used as monotherapy or in
      combination with other liver-directed therapies, can provide excellent local
      control that is cost effective. Therefore, as the HCC treatment paradigm
      continues to evolve, ablative radiation treatment has moved from a palliative
      treatment to both a "bridge to transplant" and a definitive treatment.

PMID- 29645078
TI  - Course and predictors of posttraumatic stress disorder in a cohort of
      psychologically distressed patients with cancer: A 4-year follow-up study
      methodological and statistical issues.

PMID- 29645077
TI  - A symptom-based model to predict colorectal cancer in low-resource countries:
      Results from a prospective study of patients at high risk for colorectal cancer.
AB  - BACKGROUND: Colorectal cancer (CRC) rates in low-resource countries, which
      typically lack CRC screening programs, are rising. This study determined whether
      a risk model for patients with rectal bleeding could identify patients with
      curable CRC. METHODS: This prospective, cross-sectional study evaluated a model
      constructed from data from 1 hospital and validated at 2 other hospitals. The
      primary endpoint was the ability of the model to predict CRC, as diagnosed by
      colonoscopy, from clinical characteristics. The secondary endpoint was to
      determine the percentage of patients who had CRC. RESULTS: Consecutive patients
      who were 45 years old or older and had self-reported rectal bleeding for more
      than 1 week were evaluated. From January 2014 to July 2016, 362 patients answered
      a questionnaire and underwent colonoscopy. In the validation cohort, 56% of
      patients with rectal bleeding, weight loss, and changes in bowel habits had CRC,
      whereas 2% of patients with bleeding alone did. Overall, 18.2% of the patients
      had CRC, and 8.6% had adenomas. The proportion of CRC patients with potentially
      curable stage II or III disease was 74%, whereas the historical rate was 36%. The
      combination of rectal bleeding with both symptoms significantly predicted CRC in
      the validation set (odds ratio, 12.8; 95% confidence interval, 4.6-35.4; P <
      .001). CONCLUSIONS: In low-resource settings, patients with rectal bleeding,
      weight loss, and changes in bowel habits should be classified as high risk for
      CRC. Patients with a high risk score should be prioritized for colonoscopy to
      increase the number of patients diagnosed with potentially curable CRC. Cancer
      2018;124:2766-2773. (c) 2018 American Cancer Society.

PMID- 29645079
TI  - Anti-nuclear antibodies in patients with breast cancer.
AB  - To study the prevalence of anti-nuclear antibodies (ANA) in breast cancer
      patients and its association with tumour characteristics. Ninety-one patients
      with breast mass detected by image studies and assigned to conduct diagnostic
      biopsy and eventual surgical treatment were studied for demographical, tumour
      data and presence of ANA. Serum of positive ANA patients was screened for the
      extractable nuclear antigen (ENA) profile. As comparison, 91 healthy individuals
      matched for age and from the same geographical area were included. In this sample
      72 of 91 (79.1%) had malignant lesions (83% ductal infiltrative carcinoma). ANA
      was positive in 44.4% of patients with malignant tumour and in 15.7% of those
      with benign lesions (malignant versus benign with P = 0.03). Controls had ANA
      positivity in 5.4%, and when compared with tumour samples showed P < 0.0001. The
      most common immunofluorescence pattern was a fine dense speckled pattern. In the
      ANA-positive patients with malignant lesions, seven had positivity for ENA
      profile (three for anti-RNP and anti-Sm, one for just anti-RNP, two for anti-Ro
      and anti-La e two for just anti-La). It was not possible to associate ANA
      positivity with tumour histological characteristics or staging or with patient's
      age. A negative association of ANA with hormonal (oestrogen or oestrogen plus
      progesterone) receptor status was found (P = 0.01). In this sample, there was a
      high prevalence of ANA positivity in breast cancer patients with a negative
      association with the presence of hormonal receptors. More studies are needed to
      understand the real value of this finding.

PMID- 29645080
TI  - Risk of oral tongue cancer among immunocompromised transplant recipients and
      human immunodeficiency virus-infected individuals in the United States.
AB  - BACKGROUND: Oral tongue cancer incidence has increased among whites in the United
      States; however, the cause remains unknown. If an infectious agent is implicated,
      then elevated risk would be expected among immunosuppressed individuals. METHODS:
      By using population-based registry linkage information from the US Transplant
      Cancer Match and human immunodeficiency virus/acquired immunodeficiency syndrome
      (HIV/AIDS) Cancer Match studies, the authors examined the risk of oral tongue
      squamous cell carcinoma (SCC) among immunocompromised transplantation recipients
      and HIV-infected individuals. In addition, the risks of oropharyngeal SCC
      (strongly related to human papillomavirus infection; modestly affected by
      immunosuppression), other tobacco/alcohol-related oral cavity SCCs (not thought
      to be infection/immunosuppression-related), and non-Hodgkin lymphoma of oral
      cavity/pharynx (strongly related to Epstein-Barr virus; profoundly affected by
      immunosuppression) were evaluated. RESULTS: Compared with the general population,
      the risk of non-Hodgkin lymphoma was strongly increased (standardized incidence
      ratio [SIR] > 8.0). The risk of all SCCs was modestly and similarly elevated
      among transplantation recipients (SIR range, 2.2-2.7; Pheterogeneity  = .2);
      whereas, among HIV-infected individuals, the risk of oral tongue SCC was higher
      compared with the risk of other SCCs (SIR, 3.0 vs 1.7 [for oropharyngeal SCCs]
      and 2.3 [for other oral cavity SCCs]; Pheterogeneity  < .001). The risk of SCCs
      was significantly higher among men, older individuals, and whites; and risk
      increased with the time since transplantation/AIDS onset. The risk of oral tongue
      SCC was significantly higher among HIV-infected men who have sex with men
      compared with the average risk in HIV-infected individuals (adjusted incidence
      rate ratio = 2.0). CONCLUSIONS: Similar modest increases in the risk of oral
      tongue and other oral cavity SCCs do not suggest that an infectious agent or
      exposure profoundly affected by immunosuppression underlies the increase in oral
      tongue cancer. Cancer 2018;124:2515-22. (c) 2018 American Cancer Society.

PMID- 29645081
TI  - Have we found the right patient population for transplantation in follicular
      lymphoma?

PMID- 29645082
TI  - Soluble ST2 regulation by rhinovirus and 25(OH)-vitamin D3 in the blood of
      asthmatic children.
AB  - Paediatric asthma exacerbations are often caused by rhinovirus (RV). Moreover,
      25(OH)-vitamin D3 (VitD3) deficiency during infancy was found associated with
      asthma. Here, we investigated the innate immune responses to RV and their
      possible modulation by 25(OH)-VitD3 serum levels in a preschool cohort of
      children with and without asthma. The innate lymphoid cell type 2 (ILC2)
      associated marker, ST2, was found up-regulated in the blood cells of asthmatic
      children with low serum levels of 25(OH)-VitD3 in the absence of RV in their
      airways. Furthermore, in blood cells from control and asthmatic children with RV
      in their airways, soluble (s) ST2 (sST2) protein was found reduced. Asthmatic
      children with low 25(OH)-VitD3 in serum and with RV in vivo in their airways at
      the time of the analysis had the lowest sST2 protein levels in the peripheral
      blood compared to control children without RV and high levels of 25(OH)-VitD3.
      Amphiregulin (AREG), another ILC2-associated marker, was found induced in the
      control children with RV in their airways and low serum levels of 25(OH)-VitD3.
      In conclusion, the anti-inflammatory soluble form of ST2, also known as sST2, in
      serum correlated directly with interleukin (IL)-33 in the airways of asthmatic
      children. Furthermore, RV colonization in the airways and low serum levels of
      25(OH)-VitD3 were found to be associated with down-regulation of sST2 in serum in
      paediatric asthma. These data indicate a counter-regulatory role of 25(OH)-VitD3
      on RV-induced down-regulation of serum sST2 in paediatric asthma, which is
      relevant for the therapy of this disease.

PMID- 29645084
TI  - Reply to Course and predictors of posttraumatic stress disorder in a cohort of
      psychologically distressed patients with cancer: A 4-year follow-up study
      methodological and statistical issues.

PMID- 29645085
TI  - Improving therapy for patients with epidermal growth factor receptor-mutant lung
      cancer.

PMID- 29645083
TI  - Polypharmacy and patterns of prescription medication use among cancer survivors.
AB  - BACKGROUND: The population of cancer survivors is rapidly growing in the United
      States. Long-term and late effects of cancer, combined with the ongoing
      management of other chronic conditions, make survivors particularly vulnerable to
      polypharmacy and its adverse effects. In the current study, the authors examined
      patterns of prescription medication use and polypharmacy in a population-based
      sample of cancer survivors. METHODS: Using data from the Medical Expenditure
      Panel Survey (MEPS), the authors matched cancer survivors (5216 survivors) with
      noncancer controls (19,588 controls) by age, sex, and survey year. Polypharmacy
      was defined as >=5 unique medications. The authors estimated the percentage of
      respondents prescribed medications within therapeutic classes and total
      prescription expenditures. RESULTS: A higher percentage of cancer survivors were
      prescribed >=5 unique medications (64.0%; 95% confidence interval [95% CI], 62.3%
      65.8%) compared with noncancer controls (51.5%; 95% CI, 50.4%-52.6%), including
      drugs with abuse potential. Across all therapeutic classes, a higher percentage
      of newly (<=1 year since diagnosis) and previously (>1 years since diagnosis)
      diagnosed survivors were prescribed medications compared with controls, with
      large differences observed with regard to central nervous system agents (65.8%
      [95% CI, 62.3%-69.3%] vs 57.4% [95% CI, 55.3%-59.5%] vs 46.0% [95% CI, 45.0%
      46.9%]). Specifically, nearly 10% of survivors were prescribed benzodiazepines
      and/or opioids compared with approximately 5% of controls. Survivors had more
      than double the prescription expenditures (median of $1633 vs $784 among
      controls). Findings persisted across age and comorbidity categories. CONCLUSIONS:
      Cancer survivors were prescribed a higher number of unique medications, including
      drugs with abuse potential, thereby increasing their risk of adverse drug events,
      financial toxicity, poor adherence, and drug-drug interactions. Cancer
      2018;124:2850-2857. (c) 2018 American Cancer Society.

PMID- 29645086
TI  - Erlotinib plus either pazopanib or placebo in patients with previously treated
      advanced non-small cell lung cancer: A randomized, placebo-controlled phase 2
      trial with correlated serum proteomic signatures.
AB  - BACKGROUND: This study compared the efficacy and safety of treatment with
      erlotinib plus pazopanib versus erlotinib plus placebo in patients with
      previously treated advanced non-small cell lung cancer (NSCLC). METHODS: Patients
      with progressive-stage IV NSCLC after either 1 or 2 previous chemotherapy
      regimens were randomized to receive erlotinib (150 mg by mouth daily) with either
      pazopanib (600 mg by mouth daily) or placebo. During treatment, patients were
      evaluated every 8 weeks until disease progression or unacceptable toxicity. After
      a study amendment, pretreatment serum specimens for the VeriStrat assay were
      collected. The predictive value of the VeriStrat score (good vs poor) for
      progression-free survival (PFS) and overall survival (OS) was assessed in the
      overall population and in each treatment group. RESULTS: One hundred ninety-two
      eligible patients were randomized between February 2010 and February 2011. PFS
      was prolonged with erlotinib plus pazopanib versus erlotinib plus placebo
      (median, 2.6 vs 1.8 months; hazard ratio, 0.58; P = .001). There was no
      difference in the OS of the 2 groups. A good VeriStrat score predicted longer PFS
      and OS in the entire group and predicted longer PFS in the subgroup receiving
      erlotinib plus pazopanib. The addition of pazopanib increased toxicity, and this
      was consistent with the known toxicity profile. CONCLUSIONS: The addition of
      pazopanib to erlotinib in an unselected group of patients with previously treated
      NSCLC improved PFS and increased treatment-related toxicity, but it had no
      influence on OS. The efficacy of both regimens was modest. Patients receiving
      erlotinib plus pazopanib had longer PFS if they had a good VeriStrat score versus
      a poor one. Cancer 2018;124:2355-64. (c) 2018 American Cancer Society.

PMID- 29645090
TI  - Multiple zinc ions maintain the open conformation of the catalytic site in the
      DNA mismatch repair endonuclease MutL from Aquifex aeolicus.
AB  - The DNA mismatch repair endonuclease MutL consists of N-terminal ATPase and C
      terminal endonuclease domains. The endonuclease domain binds zinc ion, although
      the ion seems not to function as a catalytic metal ion. Here, we solved the
      crystal structures of the Aquifex aeolicus MutL (aqMutL) endonuclease domain
      complexed with a single and three zinc ions. Differences between the two
      structures show that binding of multiple zinc ions induces a closed-to-open
      conformational change at the catalytic site. It is also revealed that the three
      zinc-bound form of the endonuclease domain exhibits higher endonuclease activity
      than the single-zinc-bound form. These results indicate that multiple zinc ions
      are required for the proper folding of the endonuclease domain, which would
      facilitate the endonuclease activity of aqMutL.

PMID- 29645089
TI  - Nitrogen enrichment suppresses other environmental drivers and homogenizes salt
      marsh leaf microbiome.
AB  - Microbial community assembly is affected by a combination of forces that act
      simultaneously, but the mechanisms underpinning their relative influences remain
      elusive. This gap strongly limits our ability to predict human impacts on
      microbial communities and the processes they regulate. Here, we experimentally
      demonstrate that increased salinity stress, food web alteration and nutrient
      loading interact to drive outcomes in salt marsh fungal leaf communities. Both
      salinity stress and food web alterations drove communities to deterministically
      diverge, resulting in distinct fungal communities. Increased nutrient loads,
      nevertheless, partially suppressed the influence of other factors as determinants
      of fungal assembly. Using a null model approach, we found that increased nutrient
      loads enhanced the relative importance of stochastic over deterministic divergent
      processes; without increased nutrient loads, samples from different treatments
      showed a relatively (deterministic) divergent community assembly whereas
      increased nutrient loads drove the system to more stochastic assemblies,
      suppressing the effect of other treatments. These results demonstrate that common
      anthropogenic modifications can interact to control fungal community assembly.
      Furthermore, our results suggest that when the environmental conditions are
      spatially heterogeneous (as in our case, caused by specific combinations of
      experimental treatments), increased stochasticity caused by greater nutrient
      inputs can reduce the importance of deterministic filters that otherwise caused
      divergence, thus driving to microbial community homogenization.

PMID- 29645087
TI  - A humanized TCR retaining authentic specificity and affinity conferred potent
      anti-tumour cytotoxicity.
AB  - The affinity of T-cell receptor (TCR) determines the efficacy of TCR-based
      immunotherapy. By using human leucocyte antigen (HLA)-A*02 transgenic mice, a TCR
      was generated previously specific for human tumour testis antigen peptide MAGE
      A3112-120 (KVAELVHFL) HLA-A*02 complex. We developed an approach to humanize the
      murine TCR by replacing the mouse framework with sequences of folding optimized
      human TCR variable domains for retaining binding affinity. The resultant
      humanized TCR exhibited higher affinity and conferred better anti-tumour activity
      than its parent murine MAGE-A3 TCR (SRm1). In addition, the affinity of humanized
      TCR was enhanced further to achieve improved T-cell activation. Our studies
      demonstrated that the human TCR variable domain frameworks could provide support
      for complementarity-determining regions from a murine TCR, and retain the
      original binding activity. It could be used as a generic approach of TCR
      humanization.

PMID- 29645091
TI  - Sex in the wild: How and why field-based studies contribute to solving the
      problem of sex.
AB  - Why and how sexual reproduction is maintained in natural populations, the so
      called "queen of problems," is a key unanswered question in evolutionary biology.
      Recent efforts to solve the problem of sex have often emphasized results
      generated from laboratory settings. Here, we use a survey of representative "sex
      in the wild" literature to review and synthesize the outcomes of empirical
      studies focused on natural populations. Especially notable results included
      relatively strong support for mechanisms involving niche differentiation and a
      near absence of attention to adaptive evolution. Support for a major role of
      parasites is largely confined to a single study system, and only three systems
      contribute most of the support for mutation accumulation hypotheses. This
      evidence for taxon specificity suggests that outcomes of particular studies
      should not be more broadly extrapolated without extreme caution. We conclude by
      suggesting steps forward, highlighting tests of niche differentiation mechanisms
      in both laboratory and nature, and empirical evaluation of adaptive evolution
      focused hypotheses in the wild. We also emphasize the value of leveraging the
      growing body of genomic resources for nonmodel taxa to address whether the
      clearance of harmful mutations and spread of beneficial variants in natural
      populations proceeds as expected under various hypotheses for sex.

PMID- 29645092
TI  - The adaptive value of heterospory: Evidence from Selaginella.
AB  - Heterospory was a pivotal evolutionary innovation for land plants, but it has
      never been clear why it evolved. We used the geographic distributions of 114
      species of the heterosporous lycophyte Selaginella to explore the functional
      ecology of microspore and megaspore size, traits that would be correlated with
      many aspects of a species' regeneration niche. We characterized habitats at a
      global scale using leaf area index (LAI), a measure of foliage density and thus
      shading, and net primary productivity (NPP), a measure of growth potential.
      Microspore size tends to decrease as habitat LAI and NPP increase, a trend that
      could be related to desiccation resistance or to filtration of wind-borne
      particles by leaf surfaces. Megaspore size tends to increase among species that
      inhabit regions of high LAI, but there is an important interaction with NPP. This
      geographical pattern suggests that larger megaspores provide an establishment
      advantage in shaded habitats, although in open habitats, where light is less
      limiting, higher productivity of the environment seems to give an advantage to
      species with smaller megaspores. These results support previous theoretical
      arguments that heterospory was originally an adaptation to the increasing height
      and density of Devonian vegetative canopies that accompanied the diversification
      of vascular plants with leaves.

PMID- 29645094
TI  - Leishmania amazonensis downregulates macrophage iNOS expression via Histone
      Deacetylase 1 (HDAC1): a novel parasite evasion mechanism.
AB  - The induced expression of nitric oxide synthase (iNOS) controls the intracellular
      growth of Leishmania in infected macrophages. Histones deacetylases (HDACs)
      negatively regulate gene expression through the formation of complexes containing
      transcription factors such as NF-kappaB p50/50. Herein, we demonstrated the
      occupancy of p50/p50_HDAC1 to iNOS promoter associated with reduced levels of
      H3K9Ac. Remarkably, we found increased levels of HDAC1 in L. amazonensis-infected
      macrophages. HDAC1 upregulation was not found in L. major-infected macrophages.
      The parasite intracellular load was reduced in HDAC1 knocked-down macrophages,
      which presented increased nitric oxide levels. HDAC1 silencing led to the
      occupancy of CBP/p300 to iNOS promoter and the rise of H3K9Ac modification.
      Importantly, the immunostaining of skin samples from hiporeactive cutaneous
      leishmaniasis patients infected with L. amazonensis, revealed high levels of
      HDAC1. In brief, L. amazonensis induces HDAC1 in infected macrophages, which
      contribute to parasite survival and is associated to hiporeactive stage found in
      L. amazonensis infected patients.

PMID- 29645096
TI  - Supplement Title Page.

PMID- 29645093
TI  - Autologous transplantation versus allogeneic transplantation in patients with
      follicular lymphoma experiencing early treatment failure.
AB  - BACKGROUND: Early treatment failure (ETF) in follicular lymphoma (FL), defined as
      relapse or progression within 2 years of frontline chemoimmunotherapy, is a newly
      recognized marker of poor survival and identifies a high-risk group of patients
      with an expected 5-year overall survival (OS) rate of approximately 50%.
      Transplantation is an established option for relapsed FL, but its efficacy in
      this specific ETF FL population has not been previously evaluated. METHODS: This
      study compared autologous hematopoietic stem cell transplantation (auto-HCT) with
      either matched sibling donor (MSD) or matched unrelated donor (MUD) allogeneic
      hematopoietic cell transplantation (allo-HCT) as the first transplantation
      approach for patients with ETF FL (age >= 18 years) undergoing auto-HCT or allo
      HCT between 2002 and 2014. The primary endpoint was OS. The secondary endpoints
      were progression-free survival, relapse, and nonrelapse mortality (NRM). RESULTS:
      Four hundred forty FL patients had ETF (auto-HCT, 240; MSD hematopoietic stem
      cell transplantation [HCT], 105; and MUD HCT, 95). With a median follow-up of 69
      to 73 months, the adjusted probability of 5-year OS was significantly higher
      after auto-HCT (70%) or MSD HCT (73%) versus MUD HCT (49%; P = .0008). The 5-year
      adjusted probability of NRM was significantly lower for auto-HCT (5%) versus MSD
      (17%) or MUD HCT (33%; P < .0001). The 5-year adjusted probability of disease
      relapse was lower with MSD (31%) or MUD HCT (23%) versus auto-HCT (58%; P <
      .0001). CONCLUSIONS: Patients with high-risk FL, as defined by ETF, undergoing
      auto-HCT for FL have low NRM and a promising 5-year OS rate (70%). MSD HCT has
      lower relapse rates than auto-HCT but similar OS. Cancer 2018;124:2541-51. (c)
      2018 American Cancer Society.

PMID- 29645098
TI  - Acknowledgement Text.

PMID- 29645097
TI  - Pregnancy spacing and maternal morbidity in Matlab, Bangladesh.
AB  - OBJECTIVE: The study examines the relationship between pregnancy spacing and
      seven measures of maternal morbidity in Matlab, Bangladesh. METHOD: The study
      analyzes maternal morbidity data on 11,122 women who visited a health center
      during their third trimester of pregnancy between 1996 and 2002. Adjusted odds
      ratios were obtained through logistic regression analysis to assess the effects
      of pregnancy intervals of differing lengths while holding constant other
      influences (six variables) on maternal morbidity. RESULTS: After controlling
      these variables, pre-eclampsia and high blood pressure are significantly more
      likely for women with preceding inter-pregnancy intervals of less than 6 months
      or 75 months or more compared to those with intervals of 27-50 months. Premature
      rupture of membranes is significantly more likely following inter-pregnancy
      intervals of 6-14 months, and edema is significantly more likely following inter
      pregnancy intervals over 50 months. CONCLUSION: Short and long inter-pregnancy
      intervals are associated with increased incidence of some maternal morbidities.

PMID- 29645101
TI  - One country's story: The PROALMA program in Honduras.
AB  - The first phase of the PROALMA project in Honduras resulted in changed hospital
      breastfeeding practices within as little as 2 years. These changes affected the
      community, lengthening the duration of exclusive breastfeeding to 1-2 months and
      the duration of any breastfeeding to 12 months. The second phase of the project
      sought to extend the program nationwide. One of the original pilot hospitals in
      San Pedro Sula was well along in breastfeeding promotion but felt there were
      still problems in breastfeeding education and the integration with family
      planning services. Following retraining of staff and the opening of a
      Breastfeeding Clinic and a Temporary Methods Family Planning Clinic, there have
      been improvements in both areas.

PMID- 29645103
TI  - The Brazilian national breastfeeding program: A success story.
AB  - The Brazilian National Breastfeeding Program launched in 1981, is remarkable for
      its broad scope, including activities aimed at protecting (employment
      legislation, control of marketing of substitutes for mother's milk), promoting
      (use of the media, professional training), and supporting breastfeeding (mothers'
      groups, information material, and direct counseling). The program was preceded by
      an assessment in the metropolitan areas of Recife and Sao Paulo. Evaluation of
      the program carried out in 1987-1988 shows that it has had an impact; the average
      duration of breastfeeding increased from 89 to 127 days in Sao Paulo and from 66
      to 104 days in Recife. Exclusive breastfeeding, which averaged 43 days in Sao
      Paulo, increased by 1.5 times; while in Recife the increase was 2.2 times,
      leading to 32 days.

PMID- 29645105
TI  - The use of mass media to promote breastfeeding.
AB  - Breastfeeding promotion is currently hampered by four major problems: the decline
      in funding for campaigns; failure to use mass media; lack of program evaluation;
      and vague messages. Thorough social marketing research could determine why women
      are turning away from breastfeeding and what messages could be used to make
      breastfeeding a more attractive feeding option. Similar efforts should be made to
      include breastfeeding messages in other programs, such as family planning, growth
      monitoring, and oral rehydration therapy.

PMID- 29645107
TI  - Technical working groups C and D reports.
AB  - The discussion following the reports of Technical Working Groups C and D centered
      on the advantages of various next steps: a breastfeeding focal point; national
      commissions; other needs.

PMID- 29645110
TI  - Breastfeeding and health care services.
AB  - Breastfeeding can help prevent the 38,000 daily deaths of infants and young
      children through its nutritional, immunologic, and sanitary aspects.
      Nevertheless, it is on the decline in most countries. The World Health
      Organization (WHO) and United Nations Children's Fund (UNICEF) have combined to
      issue guidelines on the role of maternity services in promoting breastfeeding,
      such as, a hospital breastfeeding policy with rooming-in, demand-feeding, and the
      elimination of bottles and breast milk substitutes. These practices have
      succeeded in programs around the world and have increased the breastfeeding rate
      at the same time that infection rates decreased.

PMID- 29645111
TI  - Breastfeeding in systems related to health care.
AB  - The discussion following this panel's presentations centered on the contributions
      of mothers' support groups; aspects of training and promotional messages;
      dissemination and exchange of information; and working women and breastfeeding.

PMID- 29645113
TI  - Statement on breastfeeding and diarrhea prevention and treatment.

PMID- 29645114
TI  - The need for action.
AB  - Nutrition workers speculated about why poor mothers should decide to bottle feed,
      when their community in the past had apparently always breastfed effortlessly and
      successfully. Surveys cross-tabulated feeding methods against socioeconomic
      variables, but it was difficult to make use of the results. Few thought that
      there was anything we needed to learn about HOW to make breastfeeding succeed.
      There was also a tacit assumption that if you had the resources - for example if
      you were yourself an employed health worker - you could bottle feed safely, so
      there was no need to worry.

PMID- 29645117
TI  - Government and social support for breastfeeding: Industrialized countries.
AB  - The discussion following Dr. Helsing's presentation centered on the role of
      feminist groups and research questions.

PMID- 29645115
TI  - Recommendations on breastfeeding promotion among pediatricians.
AB  - Pediatricians often have to treat the severely ill child whose symptoms could
      have been prevented by exclusive breastfeeding. Nevertheless quite a few
      pediatricians continue to pass on inappropriate advice on breastfeeding or lack
      the commitment to its promotion. This paper lists the obstacles that were
      encountered in breastfeeding promotion among pediatricians in India and gives 17
      recommendations for overcoming them.

PMID- 29645119
TI  - Appendix 1: Participants.

PMID- 29645118
TI  - Breastfeeding and growth monitoring.
AB  - One of the main reasons women stop breastfeeding is they lack confidence in their
      ability to produce enough milk. Growth monitoring gives them the confidence by
      showing their baby's satisfactory growth. There are ten pitfalls to growth
      monitoring programs however: (1) the emphasis on a curative rather than a
      preventive approach; (2) monitoring starts too late; (3) programs emphasize
      nutritional status rather than growth status; (4) the chart is not used to prompt
      a dialogue with the mother on meaning; (5) health workers do not listen to find
      out why some babies are succeeding and others are not; (6) insufficient attention
      is paid to training and supervision, and programs should address the child's
      total environment; (7) growth monitoring is seen as isolated from other aspects
      of health care; (8) the community should become involved in addressing growth
      problems; (9) additional food is often seen as the only activity rather than
      separating the preventive strategy of growth monitoring from the curative
      activity; and (10) growth monitoring itself achieves little unless it leads to
      growth promotion.

PMID- 29645120
TI  - Technical working groups A and B reports.
AB  - The discussion following the reports by Technical Working Groups A and B centered
      on the recommendation that a strategy meeting of top policymakers be held to
      confirm their commitment to breastfeeding; and on the advantages and
      disadvantages of an international focal point for breastfeeding efforts.

PMID- 29645122
TI  - Technical working group D report: Government and donor support for breastfeeding
      in health and health-related programs.
AB  - The purpose of this working group was to design a general strategy for government
      and donor support for breastfeeding promotion in health-related and other non
      maternity health programs. First, it is important to examine the reasons why
      governments and donor agencies accept or reject programs to support.

PMID- 29645123
TI  - Appendix 2: Schema for the development of breastfeeding definitions.

PMID- 29645125
TI  - Introduction and summary.

PMID- 29645126
TI  - Breastfeeding promotion in maternity care services: Hospital programs as a
      catalyst to policy change.
AB  - The discussion following this panel's presentations centered on difficulties in
      gaining support from medical professionals; the importance of support from the
      top level; and the way to change hospital and breastfeeding practices, especially
      aspects of practice that are associated with postpartum amenorrhea.

PMID- 29645127
TI  - One country's story: Brazil - Breastfeeding promotion in many sectors.
AB  - The discussion following Dr. Rea's presentation centered on whether a program
      should focus more on mass media or hospital change and raised questions about
      rooming-in and evaluation.

PMID- 29645129
TI  - The commitment to breastfeeding.
AB  - The Agency for International Development (A.I.D.) is increasing its efforts to
      promote breastfeeding, as part of its child survival initiatives in child
      spacing, diarrheal disease control, and nutrition. Research suggests that
      promotion can increase breastfeeding rates. The Agency, for the first time, has
      set aside funds specifically for breastfeeding promotion and is working to
      identify places in its programs where such promotion can take place.

PMID- 29645128
TI  - Professional education and training for trainers.
AB  - There is a worldwide need for health professionals knowledgeable in lactation
      physiology and breastfeeding management. The seven step Wellstart education
      program is aimed at physician-nurse teams from teaching hospitals in developing
      nations. In its 6 years of operation, it has taught 64 such teams, whose members
      have in turn taught others in their own countries. This success demonstrates the
      possibility for a major contribution to promoting breastfeeding.

PMID- 29645130
TI  - A midwife's view of the history of modern breastfeeding practices.
AB  - The author finds that three things make breastfeeding successful: the mother's
      desire; correct positioning of the baby; and the baby's control of time at the
      breast. Restrictions of feeding time originated early in this century. Combined
      with descriptions of babies sucking from the nipple instead of the breast,
      misinformation has spread about breastfeeding in spite of correct knowledge being
      available. A review of textbooks and articles should be undertaken.

PMID- 29645131
TI  - The effect of breastfeeding promotion on the infertile postpartum period.
AB  - A new project is testing whether a breastfeeding promotion program will change
      breastfeeding behavior and the length of postpartum amenorrhea. The control group
      and 100 of the eventual 400 experimental subjects have been recruited. The
      program consists of workshops, prenatal care, maternity ward postpartum care,
      early home visits, and a breastfeeding outpatient clinic. Early results seem to
      indicate decreased use of pacifiers and foods and fluids other than breast milk
      by women in the study group.

PMID- 29645132
TI  - Supporting breastfeeding: What governments and health workers can do - European
      experiences.
AB  - The International Code of Marketing of Breast-Milk Substitutes provides health
      workers with a framework for action in breastfeeding promotion. Countries are to
      report their efforts to the World Health Organization (WHO). The European
      Regional WHO Office finds a diversity of practices within its countries.
      Therefore in 1986, they convened a meeting of health workers' organizations to
      draw up a strategy for implementation. This paper outlines the elements in the
      strategy, the reasons why some countries have seen increases in breastfeeding,
      and the possible ways international organizations can help.

PMID- 29645133
TI  - Breastfeeding promotion in family planning programs.
AB  - Family planning programs serve large numbers of women of childbearing, and thus
      breastfeeding, age. Although these programs appear to have a number of
      characteristics which would be useful for promoting and supporting breastfeeding,
      most family planning programs have done very little in this area. The Agency for
      International Development (A.I.D.) and the Institute for International Studies in
      Natural Family Planning are working to find ways to remove barriers to family
      planning breastfeeding promotion efforts. Such barriers include lack of or
      conflicting measures of program success and lack of information on the
      breastfeeding/fertility relationship. The Institute is developing guidelines to
      help family planning programs promote breastfeeding.

PMID- 29645134
TI  - Appendix 3: Protecting, promoting and supporting breastfeeding: the special role
      of maternity services - A joint WHO/UNICEF statement.

PMID- 29645135
TI  - Donor agency representative panel: Feedback and strategies.

PMID- 29645136
TI  - Breastfeeding promotion in other health programs.
AB  - The discussion following this panel's presentations centered on breastfeeding and
      diarrheal disease; problems with growth monitoring; survey questions; and
      definition difficulties.

PMID- 29645137
TI  - Statement on the immediate need for breastfeeding promotion.

PMID- 29645139
TI  - The impact of unregulated fertility on maternal and child survival.
AB  - Almost all maternal and child deaths represent merely the endpoint of the 'road
      to death' - a combination of factors that include high-risk pregnancy,
      socioeconomic disadvantage and inadequate health care. Unregulated fertility is
      the underlying cause of most high-risk pregnancies. They are: unwanted; in
      mothers younger than 20 or older than 35; closely spaced; and in women who
      already have several children. The resulting morbidity and mortality create a
      cycle of further disadvantage, further increases in child mortality and further
      high-risk pregnancies. Family planning is the single most important exit from the
      'road to death.' Over the past 40 years it has contributed to the worldwide
      reduction in child mortality, and for every 100 women provided with family
      planning, a woman's life is saved.

PMID- 29645140
TI  - HIV, STD and their current impact on reproductive health: the need for control of
      sexually transmitted diseases.
AB  - STD and HIV are the second most important cause of Disability Adjusted Life Years
      lost in women in the developing world. Reasons for this are multiple, and include
      their higher vulnerability for STD and HIV, poor health care seeking behavior and
      lack of accessible and acceptable services. There is considerable synergism
      between family welfare services and STD programs: complications and sequelae of
      STD affect the reproductive tract and child health and survival; reproductive and
      child health and survival are the focus of family welfare programs. Family
      welfare services are thus well positioned to incorporate STD and HIV prevention
      and control measures. This is feasible, although practical and logistical
      problems need to be addressed. Where indicated, pilot integration projects can
      assess the cost-effectiveness and outcome of such programs.

PMID- 29645141
TI  - The role of emergency obstetric care in preventing maternal deaths: an historical
      perspective on European figures since 1751.
AB  - A review of the time-relationships is provided between the introduction of
      obstetric techniques and organization of obstetric care in Europe and the
      decrease of maternal death rates from 1751 to 1980. Published figures were used
      to discover the evolution of maternal deaths in Europe for the last 250 years,
      and to propose a parallel analysis of major modifications of obstetric care. The
      teaching of obstetrics to midwives and general practitioners, introduction of
      forceps and of low-segment cesarean section technique, disappearance of home
      deliveries, antibiotics, anesthesia and blood banks are among the addressed
      techniques. Even if a causal relationship cannot be proposed, the major
      inflection in the rate of reduction of maternal deaths is related to the
      introduction of low segment cesarean section in the first years of the 20th
      century. This progress was also related to the progressive transfer of birth
      sites, from home to specialized units.

PMID- 29645142
TI  - Maternal mortality: national versus hospital situation.
AB  - A retrospective analysis of the causes of maternal mortality in two academic
      hospitals of Dhaka city over a 2-year period was carried out and compared with
      national figures. These are the country's chief referral institutions, where only
      the critically ill are admitted. Currently, the national maternal mortality ratio
      (MMR) is 5.6/1000 live births, while in Dhaka Medical College Hospital the case
      fatality ratios (CFR) were 24.4 and 17.2 in 1992 and 1993, respectively. In
      Mitford Hospital the CFR was 11.1 and 5.4/1000 live births, during the same
      periods. The most common cause of maternal death at the national level was
      postpartum hemorrhage and at medical college hospitals it was eclampsia. If we
      can strengthen emergency obstetric care at all levels, we can reduce maternal
      mortality bolh at the national level and at the referral hospitals.

PMID- 29645143
TI  - Unmet need in family planning in South Asia Region.
AB  - Today's population in South Asia is estimated at 1.2 billion. With an average
      annual growth of 2%, it increases by more than 24 million people each year, the
      highest increment in the world. Despite recent improvements in the contraceptive
      prevalence rate, all countries in the region experience high levels of unmet need
      for contraception, Several of the region's characteristics have a bearing on the
      challenge of promoting and providing family planning services: women's status is
      particularly low; the persistence of son preference results in higher female than
      male mortality at all ages; the young age structure means an increasing number of
      people entering childbearing ages. Being predominantly rural, the region
      experiences shortages of trained health personnel as well as major problems of
      accessibility to basic health services.

PMID- 29645144
TI  - Rethinking the role of the risk approach and antenatal care in maternal mortality
      reduction.
AB  - In developing countries where most women are not delivered in health facilities,
      screening for obstetric risk is neither a cost-effective nor efficient strategy
      for maternal mortality reduction. Antenatal care can contribute to preventing
      such deaths when used for identifying early obstetric complications, educating
      women to identify obstetric danger signs, and motivating them and their families
      to seek appropriate referral care.

PMID- 29645145
TI  - Natural sex selection for safe motherhood and as a solution for population
      control.
AB  - For Safe Motherhood wanted children should be of desired sex. As Y sperm have a
      shorter life span and migrate faster, if coitus occurs before ovulation, sperm
      must wait in the tube for the ovum to arrive. By the time the ovum arrives, Y
      sperm have died and X sperm fertilize the ovum, resulting in a baby girl. If
      coitus takes place after ovulation when the ovum is waiting in the tube, the
      faster migrating Y sperm fertilize the ovum resulting in a baby boy. Eighty women
      wishing to test this hypothesis by basal body temperature and ultrasound were
      recruited. Correct results have so far been obtained in 97%. This theory can be
      used for Safe Motherhood, for population control and to eliminate sex-linked
      genetic disorders. It can also prevent both female feticide and infanticide in
      some cultures.

PMID- 29645146
TI  - Discussion.

PMID- 29645147
TI  - Birth control counseling for HIV seropositive pregnant women.
AB  - Testing for HIV antibody at the antenatal clinic in Siriraj Hospital started on 1
      July 1991. It was found that the percentage of HIV seropositive pregnant women
      rapidly increased from 1.2% in 1992 to 1.9% in 1993. During those 2 years, 487
      seropositive women were admitted for delivery or abortion; 23.8% were adolescents
      and 47.0%, young adults. Prevention of HIV transmission from mother-to-baby was
      birth control; 95 women (19.5%) chose to abort their pregnancy. After termination
      of all pregnancies by abortion or delivery, 83% requested sterilization, 12.9%
      accepted Norplant, 1.8% the pill and only 2.3% refused anything at all. Condoms
      were used regularly for prevention of HIV infection by 29.4% of men although Thai
      men generally do not accept them for birth control. Seropositive Norplant users
      had more bleeding than general Norplant users but treatments were the same.

PMID- 29645148
TI  - Discussion.

PMID- 29645149
TI  - The Mother-Baby Package: an approach to implementing safe motherhood.
AB  - The basic objectives of the Mother-Baby Package are neither new nor controversial
      - they are considered the 'four pillars' of Safe Motherhood: (1) family planning 
      to ensure that individuals and couples have the information and services to plan
      and space pregnancies; (2) antenatal care - to ensure that complications of
      pregnancy are detected as early as possible and treated appropriately; (3)
      clean/safe delivery - to ensure that all birth attendants have the knowledge,
      siwills and equipment to perform a clean and safe delivery; (4) essential
      obstetric care - to ensure that essential care is made available to all women who
      need it. Complications during pregnancy and childbirth affect not only the women
      but their newborns as well. The woman and the fetus, the mother and the neonate,
      should be seen as a dyad - two units treated as one. Poorly managed pregnancies
      and/or deliveries and/or inadequate care of neonates during the first critical
      hours of life account for significant numbers of perinatal and neonatal deaths.
      Each intervention of the Package can be appropriately applied at community,
      health center and hospital levels. Only by providing this continuum of care from
      the community through to the referral hospital will significant impact on
      mortality be achieved. The goals of the Package are, by the year 2000, to reduce
      maternal mortality by half and neonatal and perinatal mortality by 30-40% of 1990
      levels.

PMID- 29645150
TI  - Levels and determinants of maternal morbidity: results from a community-based
      study in southern India.
AB  - This analysis is based on detailed interviews with 3600 rural and urban women in
      southern India. They were younger than 35 and had at least one child less than 5
      years of age. Each woman was questioned by a trained female interviewer and asked
      about problems she had encountered during the last pregnancy. Approximately two
      fifths (41%) reported at least one morbid condition associated with that event.
      About one-fifth (18%) had had at least one problem during the antenatal period
      and delivery and another 23% indicated problems during the postpartum. Surgical
      interventions were made in 13.1% of all deliveries. However, if we consider only
      those taking place in hospital, more than one-third (34.2%) were delivered
      surgically. The relationship between socioeconomic and demographic factors and
      reported maternal morbidity has been examined by using multivariate statistical
      techniques. The policy implications of the study are discussed.

PMID- 29645151
TI  - Training of traditional birth attendants: success and failure in Bangladesh.
AB  - In Bangladesh, training of traditional birth attendants (TBAs) began in 1978.
      Since then, the government has prepared over 44000 TBAs. A few thousands more
      have received instruction through the efforts of various non-governmental
      organizations in the country. The objective of TBA training is primarily to
      change their practices of conducting deliveries. They are taught cleanliness so
      that maternal and infant mortality, which is significantly high among South and
      South East Asian nations, may be checked. The writer has herself learned from
      graduates of the course that they have received sufficient guidance and direction
      towards performing safe deliveries, a concept totally lacking until that
      experience. TBAs are thereby in a position to contend with the prevailing
      socioeconomic and cultural beliefs of the country's rural masses, and to cope
      with their problems.

PMID- 29645152
TI  - Practical issues in Safe Motherhood: Proceedings of the Fifth International
      Conference for Maternal and Neonatal Health in Dhaka, Bangladesh, November 25-30,
      1994.

PMID- 29645154
TI  - Discussion: TBA training program.

PMID- 29645153
TI  - The national maternal mortality study of Egypt 1992-1993.
AB  - The study was designed as a population-based sample of all maternal deaths over a
      one-year period in 21 governorates. A sample of 7487 deceased women of
      reproductive age was selected. During pregnancy, delivery, or in the puerperium,
      there were 825 772 maternal deaths and 53 from incidental causes. Of the maternal
      deaths, 69.5% were due to direct obstetric causes while 26.9 and 3.6% were due to
      indirect and unknown causes, respectively. The national maternal mortality ratio
      was 174 maternal deaths per 100 000 live births.

PMID- 29645155
TI  - Antenatal risk screening and scoring: a new look.
AB  - At the individual level, risk assessment is fundamental to antenatal care. But at
      the program level, there are real difficulties associated with it, of which the
      most important is the false negatives - women with no (or few) risk factors who
      experience complications. This paper evaluates several commonly used indicators
      of risk in terms of both maternal (cephalopelvic disproportion) and fetal (low
      birthweight/prematurity) outcomes. The literature shows that obstetric history is
      a better measure of risk than so-called demographic variables like age and
      parity. When assessing the utility of a risk factor, Us sensitivity must be
      evaluated against the likelihood of false negatives. If risk assessment is
      practiced effectively, it must include a means of ensuring prompt treatment for
      low risk women with (unexpected) complications.

PMID- 29645156
TI  - A 5-year study of maternal mortality in Faisalabad City Pakistan.
AB  - A 5-year study (1989-1993) of 215 maternal deaths in Faisalabad (third largest
      city of Pakistan) is presented. There were 276 717 live births recorded by the
      Municipal Corporation during that period, giving a maternal mortality of
      0.77/1000 live births. These deaths included 88 (40.9%) in teaching hospitals, 70
      (32.6%) at home and 57 (26.5%) in private hospitals. The main causes of maternal
      death were postpartum hemorrhage, 50 (23.3%), followed by pregnancy induced
      hypertension/eclampsia and non-obstetric causes, 34 (15.8%) each. The study
      reveals that traditional birth attendant (TBA) training/refresher courses,
      intensive community education, antenatal checkup in local areas, free obstetric
      flying squad service, better linkage between formal and informal health services,
      home maternal death condolence camps and improvement of obstetric care in
      hospital, offered free for deserving cases have played major roles in reducing
      maternal mortality.

PMID- 29645157
TI  - How effective is antenatal care to promote maternal and neonatal health?
AB  - Antenatal care is effective, but relies heavily on the sympathetic attitude of
      health personnel. Essential to its promotion is community participation and
      involvement of family members. Transportation to a well-equipped facility for
      emergency obstetric care is a critical element. The effectiveness of antenatal
      care to reduce maternal morbidity and mortality from certain major causes is
      reviewed.

PMID- 29645158
TI  - Traditional birth attendants in Bangladeshi villages: cultural and sociologic
      factors.
AB  - World Health Organization policy for some years has emphasized working through
      traditional birth attendants as the best path to improving the appalling level of
      maternal and child mortality and illness in much of the Third World. The
      universal appropriateness of this strategy has begun to be called into question.
      Recent research on childbirth in rural Bangladesh, as elsewhere in South Asia,
      suggests that the concept of the 'traditional birth attendant' in the context of
      this region needs to be reexamined. The dai typically have tittle training and
      low status, due to their close association with the removal of birth pollution. A
      policy based on converting them into modern health professionals faces serious
      obstacles. In practice, neither the poorly-trained village dai nor such
      biomedically-trained practitioners as are available at the village level are able
      to deliver competent health care. Their effectiveness is further compromised by
      the cultural and material environment within which they operate. A more adequate
      approach to care for birthing women in the village still has to be developed.

PMID- 29645159
TI  - Social and cultural factors leading to mothers being brought dead to hospital.
AB  - In a 12-year period (1981-1992) 150 pregnant or recently delivered women were
      dead when they reached the hospital. Relevant history with emphasis on the events
      of the previous 24 h and the reasons for delay in reaching the hospital were
      obtained from the relatives accompanying the patient. The probable cause of death
      was determined on the basis of history only; no autopsies were done. The causes
      of delay were economic (54), sociocultural factors (51) and inadequate maternal
      services (31). In 14 cases the reasons for delay could not be established. The
      medical problems were either preventable or treatable if managed in time. A
      combination of economic, social and cultural factors played a more significant
      role in these deaths than medical causes.

PMID- 29645160
TI  - Emergency obstetric care: measuring availability and monitoring progress.
AB  - To reduce maternal deaths substantially, the facilities for Emergency Obstetric
      Care (EOC) must exist, be accessible, be utilized by complicated cases and be
      successful. Accordingly, a new set of indicators, viz., number of functional EOC
      facilities, geographic bed distribution within a district, proportion of expected
      births and expected complications managed at these units, and case fatality rate
      for complicated cases, were assessed in ten districts drawn from ten major states
      of India. The paper discusses the findings and some of the problems of data
      collection and interpretation. In general, maldistribution of beds within the
      district, low levels of cesarean section rates and, sometimes, high case fatality
      point to a need for an improvement in availability, distribution and quality of
      EOC. Similarly, low institutional birth rate and much lower than expected number
      of complications reaching the facilities point to the need for encouraging
      families to use them. Changes in these indicators over time will help gauge
      improvements in provision and utilization of EOC. The study findings and
      methodology are serving as an important element for developing a monitoring
      system for EOC under Safe Motherhood in India.

PMID- 29645161
TI  - Lessons learned from maternal mortality study to reduce deaths in Egypt.
AB  - To identify causes of maternal death in Egypt and with that knowledge to effect
      its reduction, the Ministry of Health launched a study, a unique aspect of which
      was exploration of avoidable factory at home, in medical facilities, and during
      transportation from one to the other. The country must make better use of
      existing personnel and buildings.

PMID- 29645162
TI  - Eclampsia: modern outlook on prevention and treatment.
AB  - This is a review article. Eclampsia is an almost preventable condition. The ratio
      of prostacycline and thromboxane is reversed in patients with preeclampsia and
      eclampsia. Lipid peroxides are also increased during pregnancy and there is lack
      of invasion of the spiral arteries by trophoblasts, particularly the second wave.
      A good predictive test is urgently needed to detect patients who are at risk of
      developing these conditions later in their pregnancy. Low-dose aspirin is a
      promising preventive therapy in this group of women. Until we have good means of
      preventing preeclampsia and eclampsia, supportive care in treatment must be
      improved. Essential obstetric care (EOC) at all levels of health services should
      be established to reduce maternal mortality and morbidity from this condition,
      and the community educated and mobilized to respond appropriately in time of
      need.

PMID- 29645163
TI  - Program participants.

PMID- 29645164
TI  - Severe anemia of pregnancy, recent experience.
AB  - We undertook this study to determine the current prevalence of anemia in
      pregnancy and its impact on maternal and perinatal mortality and morbidity, and
      to suggest ways to make the anemia prevention programs more effective. The
      incidence of pregnancy anemia was determined by a population-based survey (1990
      1994) of rural and urban areas using a cluster sample design. Mortality and
      morbidity data were gathered from our own hospital records (1982-1994). The
      survey data showed that 86.1% of pregnant women (n = 4752) were anemic (Hb < 11
      g/dl); 56.0% had severe anemia (Hb < 7 g/dl); and 1.9% were decompensated (Hb < 4
      g/dl). The hospital-based analysis revealed that severe anemia contributed to
      34.5% of all maternal deaths (case fatality ratio = 1769). Hypertensive disorders
      were found in 28.2% of severe anemia cases. The incidence of preterm labor was
      31.2% in these cases and the birthweight 2.23 +/- 1.13 kg (mean +/- SD), while
      perinatal mortality was 65 compared to overall rates of 7.9%, 2.78 +/- 1.32 kg
      and 46, respectively. We conclude that severe anemia of pregnancy is still
      rampant and its adverse consequences remain unabated. The risk-care approach is
      advocated as an alternative strategy.

PMID- 29645165
TI  - Family planning in Sub-Saharan Africa: present status and future strategies.
AB  - Africa lags behind the rest of the developing world in most demographic, health
      and economic indicators of social development, but some progress has been made in
      contraceptive prevalence and fertility decline. Many challenges remain for
      governments on that continent to meet the basic reproductive health needs of
      their rapidly growing populations. With the sustained support of the
      international community, there is reason to be hopeful.

PMID- 29645166
TI  - Neonatal tetanus: review of progress.
AB  - The target set for elimination of neonatal tetanus (NT) is less than one case par
      1000 live births in every district of the world. NT will then be considered to
      have been removed as a major public health problem and fewer than 150 000 cases
      are expected to occur annually worldwide if the achievements are maintained. It
      is estimated for 1993 that over 700 000 neonatal deaths due to tetanus were in
      fact prevented by maternal immunization and clean delivery practices. About 480
      000 (70%) of them were averted in only three countries: India, Bangladesh and
      Indonesia. Meanwhile, 91 others already have an estimated NT rate below 1 per
      1000 live births nationwide. Of these, 50 countries may already have achieved the
      target in each of their districts. According to 1993 estimates half a million
      newborn deaths due to tetanus are still occurring worldwide, 80% of them in 12
      countries. Out of 14 others where NT remains a major public health problem, 12
      are in the African Region. Together, these 26 countries contribute 90% of the
      global incidence of NT. By 1995, major strides towards the elimination of NT can
      be made by using the high risk approach and immunization, including organizing
      Days of Tranquility where necessary. But for this to be accomplished, there must
      be sufficient political commitment and financial support of some US$ 30 million
      to carry out the program in the 26 priority countries.

PMID- 29645167
TI  - Midwives and the achievement of safer motherhood.
AB  - The root problem of unsafe motherhood in developing countries is lack of access
      to a competent care-giver throughout pregnancy, childbirth and the postpartum
      period. These resources, trained midwives, with or without prior nursing
      training, should be recruited from the communities they are to serve. Community
      midwives must be involved in any realistic strategic plan to provide this needed
      midwifery care.

PMID- 29645168
TI  - Removing risk from safe motherhood.
AB  - It is necessary to differentiate between complications of pregnancy and
      population risk groups for those complications. The latter have limited use as
      most complications occur in the low risk groups. Complications of pregnancy need
      to be treated in health facilities that can provide blood transfusions, cesarean
      section, removal of placenta and induction of labor. A plan must exist for each
      pregnant woman to be moved to such a facility, since it is not possible to
      predict who will have the complication. Early detection and effective treatment
      of complications and family planning services to prevent unwanted pregnancies is
      the way to lower maternal mortality.

PMID- 29645171
TI  - The evolution of methods for female sterilization.
AB  - Methods for the sterilization of women by occlusion of the Fallopian tubes have
      evolved by changes in the approaches to the tubes and trials of various methods
      for occluding the tubal lumen. Approaches to the tube have included: the anterior
      abdominal wall routes by laparotomy, minilaparotomy and laparoscopy; a vaginal
      approach through the posterior vaginal fornix; and transcervical approaches,
      either blind, or via the hysteroscope. Methods for obtaining tubal occlusion have
      included: excision and suture techniques; electrocautery; clips and rings;
      intratubal occlusive devices and chemicals introduced into the tubal lumen. The
      development of each of the approaches to the tube and of the methods for
      obtaining tubal occlusion are discussed.

PMID- 29645174
TI  - The potential for improved abdominal procedures and approaches for tubal
      occlusion.
AB  - Methods of sterilization by the abdominal route are reviewed. There are wide
      variations in practice which reflect experience, training and resources in
      different countries. Clip sterilization comes nearest to fulfilling the criteria
      of a satisfactory method, whether performed by laparoscopy or minilaparotomy. The
      development of the Cambridge clip seems to offer the prospect of a significant
      improvement in reliability and safe application while microlaparoscopy and a
      smaller clip would facilitate the use of local anesthesia and decrease morbidity.

PMID- 29645178
TI  - Introduction.

PMID- 29645180
TI  - Supplement Title Page.

PMID- 29645181
TI  - Half Title.

PMID- 29645182
TI  - Copyright Page.

PMID- 29645183
TI  - FIGO Board.

PMID- 29645186
TI  - Panel discussion.

PMID- 29645194
TI  - An introduction to the supplement.

PMID- 29645195
TI  - Quinacrine sterilization (QS) in Syria: a preliminary report on 297 cases.
AB  - OBJECTIVES: To evaluate the safety, efficacy and acceptability of quinacrine
      sterilization (QS) in Syria. METHODS: From July 2001 to December 2002, 297 women
      who requested permanent sterilization volunteered for QS either in my private
      practice or my local family planning center in Aleppo, Syria. The standard
      protocol was used: 252 mg of quinacrine in the form of 7 pellets are deposited at
      the uterine fundus withy a modifeid CuT IUD inserter during the proliferative
      phase of the menstrual cycle. This procedure is repeated 4 weeks later. DMPA was
      injected at the time of the first insertion for temporary contraception. Every
      sterilized woman has had a monthly checkup visit until the cut-off date for this
      report, including a beta HCG pregnancy test. All procedures were performed by the
      author. The cut-off date for this report was June 11, 2003. RESULTS: The single
      pregnancy was ectopic. Four women (1.3%) complained of severe pain. Moderate pain
      was experienced by 13.1% while the remaining women felt mild pain, all easily
      treated. The remaining side effects were minor and also easily treated.
      Oligomenorrhea and amenorrhea affected 29% of the women and lasted for several
      months. Immediate side effects are similar to reports from other researchers.
      CONCLUSIONS: Results thus far regarding efficacy are encouraging. QS has proven
      to be acceptable.

PMID- 29645202
TI  - Quinacrine sterilization (QS) experience in the Philippines: a preliminary
      report.
AB  - OBJECTIVE: The first clinical trial of Quinacrine Sterilization (QS) in the
      Philippines was undertaken in Ceby City on January 10, 2000, to evaluate the
      accetability, safety, effectiveness and side effects of this technology. We
      intend to recruit 500 patients to utilize this technique for limiting family
      size. For the purposes of this report, our cut-off date is April 11, 2003.
      METHODS: Over more than two years, QS was performed on 36 volunteer patients.
      After careful explanation of the procedure and given the opportunity to ask
      questions, they had signed an informed consent. The trial involved transcervical
      insertion of 252 mg quinacrine in the form of pellets, and placed at the tip of
      the uterine fundus on two occasions, a month apart. Condoms were routinely
      provided to all patients except those on oral contraceptive pills and DMPA after
      the first insertion to be used for six weeks after the second one. As the numbers
      are small, no statistical evaluation was called for. RESULTS: The accumulated
      experience was 515 woman-months. There were no pregnancies, neither ectopic nor
      intrauterine. Adverse events (AE) were mild. Some patients complained of a yellow
      discharge and itching. Fifty percent experienced midl abdominal discomfort which
      was easily managed with mefenamic acid. CONCLUSIONS: Although this is a small
      study, we believe that QS is both safe and effective and we are strongly
      encouraged to continue to offer this nonsurgical sterilization method to our
      patients.

PMID- 29645206
TI  - 8-year follow-up in a randomized trial of one vs two transcervival insertions of
      quinacrine pellets for sterilization in Indonesia.
AB  - OBJECTIVE: To evaluate the efficacy of one vs two insertions of quinacrine and
      the long-term safety of quinacrine sterilization (QS) 8 years after the procedure
      in Indonesia. METHODS: Between March 1993 and September 1995, a randomized trial
      was conducted in 6 academic centers in Indonesia. In February 2003, a follow-up
      was undertaken in Bandung, one of these centers. This survey required a home
      visit of each woman. A questionaire was designed to elicit information regarding
      current general health status, method failure, pregnancy outcomes and other
      contraceptive methods now used by women who experienced failures. Among the 70
      patients receiving a single insertion of quinacrine pellets, 14.3% had become
      pregnant. There were no pregnancies among the 30 who received 2 insertions. All
      the women were found to be in good health. No long-term side effects or
      complications were identified. CONCLUSIONS: The two-insertion protocol is
      unmistakably superior to the single insertion. This study provides further
      evidence that QS is a safe contraceptive method.

PMID- 29645207
TI  - 25 years of quinacrine sterilization experience in Chile: review of 2,592 cases.
AB  - OBJECTIVES: To assess short-term side effects, long-term risks and efficacy of
      quinacrine sterilization (QS) in Chile. METHODS: Review experience of 2,592 cases
      sterilized with 2 or 3 transcervical insertions of 252 mg quinacrine as pellets
      since 1977; review the Chilean pre-clinical experience and epidemiological
      studies on cervical, endometrial and other cancers. RESULTS: Among 2,592 women
      who underwent QS, the total number of pregnancies was 119 (4.6%); 59 (49.5%) were
      carried to term with no birth defects related to QS. Nine cases were ectopic
      pregnancies. The ectopic pregnancy risk per 1,000 woman-years was 0.41, similar
      to that for surgical sterilization. The cumulative life-table pregnancy rates per
      100 women at 10 years varied from 5.2 to 6.9. Mild and transient side effects
      were reported in 13.5% of quinacrine intrauterine insertions and pelvic
      inflammatory disease was diagnosed in 4 cases (0.15%). Long-term follow-up of
      quinacrine-sterilized patients shows no increased risk of cervical, endometrial
      or other cancer. CONCLUSIONS: QS efficacy at 10 years is comparable to widely
      accepted tubal clip and single point bipolar electrocoagulation laparoscopic
      procedures. QS has a low risk of serious, immediate side effects. No long-term
      risks have been identified after 25 years of use.

PMID- 29645208
TI  - An FDA phase I clinical trial of quinacrine sterilization (QS).
AB  - OBJECTIVE: To review the significance of a United States Food and Drug
      Administration (FDA) approved Phase I clinical trial of a new use for an old
      drug, quinacrine. To discover whether ultrasound may have utility in quinacrine
      sterilization (QS). METHOD: This clinical trial began on 16 September 2000 at the
      Women's and Children's Hospital of Buffalo (WCHOB) in Buffalo, New York. Ten
      patients volunteered to have QS. These subjects were carefully followed with
      regularly scheduled examinations, including extensive laboratory blood tests. In
      addition, each patient had a trans-abdominal ultrasound examination six weeks or
      later past the date of the second insertion of quinacrine. The trial was
      completed on 30 April 2003. RESULTS: Laboratory results fell within normal
      limits, thus providing additional evidence to affirm the lack of toxic effects of
      QS. With ultrasound, we were able to see scars in both oviducts on all of our
      patients. One patient with a small scar as seen on ultrasound became pregnant.
      CONCLUSION: QS was found to be safe and effective. Ultrasound holds the promise
      of reducing the failure rate.

PMID- 29645209
TI  - The effect of special training for quinacrine sterilization (QS) in Faisalabad,
      Pakistan: a report on an 1833-women subset of 11,000 cases.
AB  - OBJECTIVE: To determine the impact of retrained clinicians on the efficacy of
      transcervical quinacrine sterilization. METHOD: Retraining of clinicians in the
      accepted insertion technique was conducted in 1996. From 1 January 1997 through
      2001, they performed 1089 quinacrine sterilizations in 11 MCH clinics of the
      Mother & Child Welfare Association at Faisalabad, Pakistan. Of these, 885 women
      had a recorded follow-up visit (81.4%) by 31 December 2001. RESULTS: Reported
      pregnancy failures declined after retraining from 5.4% (SE 2.3) for one year of
      use to 1.1% (SE 0.4) for 5 years of use. The rates at 4 years of use showed the
      expected increase in failures for women 30 years old or younger of 1.5% (SE 0.7)
      compared to 0.9% (SE 0.4) for those over 30; a lower rate of 0.8% (SE 0.4) for
      breastfeeding subjects and 2.2% (SE 1.1) for mothers not breastfeeding; but rates
      were similar for uterine length and post insertion traumatic bleeding.
      CONCLUSION: Quinacrine sterilization appears safe with acceptable efficacy.

PMID- 29645210
TI  - Forward.

PMID- 29645211
TI  - Quinacrine sterilization: a retrospective.
AB  - OBJECTIVE: To trace development of quinacrine sterilization (QS). METHODS: Review
      of published reports. RESULTS: The high prevalence of septic abortion among high
      parity women in Santiago, Chile, motivated Zipper to find a safe, inexpensive
      method of non-surgical female sterilization. Various cytotoxic drugs were tried
      in rats. Because quinacrine was already accepted for intrapleural injection it
      was chosen for the first clinical trial. A slurry consisting of quinacrine and
      xylocaine was instilled into the uterine cavity with a transcervical syringe.
      Reasonable efficacy was noted and a limited scar of the intramural tube
      demonstrated. However, a side effect of cortical excitation and reports of 3
      deaths ended this approach. Zipper and Wheeler hypothesized that the difficulty
      was due to rapid absorption of quinacrine under pressure and designed a pellet
      form that dissolves slowly and could be delivered transcervically using a
      modified IUD inserter. A standard protocol of 252 mg in seven 36 mg pellets
      placed at the uterine fundus on two occasions a month apart has now been widely
      used with considerable evidence for safety and efficacy. Indeed, protection is
      greater than 98% at 2 years of use. CONCLUSION: QS is ready for widespread use,
      especially where surgical sterilization is not safely available or when women are
      poor candidates for surgery or have such a fear of surgery that they will not
      seek surgical sterilization.

PMID- 29645212
TI  - Quinacrine sterilization in Libya: 200 cases.
AB  - OBJECTIVE: Document the safety, effectiveness and acceptability of quinacrine
      sterilization (QS) as an alternative to surgical sterilization in Libyan women.
      METHODS: This study was initiated 1 October 1998 at the Misurata Central Hospital
      and Lamis Clinic. Patient intake was completed 30 September 2002. The cut-off
      date for this analysis was 31 December 2002. A total of 200 women were given 2
      doses, each consisting of 252 mg of quinacrine hydrochloride in the form of 7
      pellets inserted one month apart. They were placed at the uterine fundus during
      the proliferative phase of the menstrual cycle using a modified IUD inserter.
      Women were asked to report any unusual observations or side effects and
      instructed to use a barrier method or safe period for one month from the time of
      the first insertion. Follow-up was scheduled at 3, 6 and 12 months after the date
      of the second insertion and every 6 months thereafter. RESULTS: Sixty-six women
      have been monitored for up to 3 years and follow-up of all patients continues.
      There has been no loss to follow-up. No side effects of any consequence have been
      reported. Thus far, no pregnancies have been reported for this protocol.
      CONCLUSIONS: Findings in this study are consistent with those seen in other
      countries. QS has been shown to be safe, effective and acceptable among Libyan
      women.

PMID- 29645213
TI  - Quinacrine sterilization (QS) in a private practice in Daytona Beach, Florida: a
      preliminary report.
AB  - OBJECTIVES: To affirm that WS can be performed safely and effectively in a U.S.
      private office practice. METHODS: The U.S. FDA Modernization Act of 1997 Pharmacy
      Compounding Provisions made it possible for American physicians to begin offering
      WS to their patients. These provisions became effective November 21, 1998. This
      series was initiated in October 2000. The standard protocol recommended by the
      International Federation for Family Health (IFFH) is followed. Information on
      patients is recorded on forms suggested by IFFG to accomplish good post-marketing
      surveillance. The potential role of uterine septae in WS failures is of
      particular interst to this investigator. RESULTS: Seven cases have been
      completed. There have been no failures. Side effects have been minor. Women have
      been exceptionally happy with this method. The Florida Agency for Health Care
      Administration has examined WS and found it to be an acceptable off-label use of
      quinacrine. CONCLUSION: Preliminary results have been similar to those reported
      by QS researchers around the world.

PMID- 29645214
TI  - A comparison of quinacrine sterilization (QS) and surgical sterilization (TL) in
      600 women in Guizhou Province, China.
AB  - OBJECTIVES: Compare the safety and efficacy of quinacrine sterilization (QS) and
      surgical sterilization, also known as tubal ligation (TL). METHODS: 300 women
      accepted QS in Guiyang, China during the period from July 1995 to September 1997.
      Each patient was scheduled for follow-up at 3, 6, 12 and 24 months. In March
      1998, a comparison group of 300 women electing TL during the same time period was
      systematically chosen. Researchers visited the village of every woman and
      conducted a structured interview. Each candidate was given a general health and
      pelvic exam at a clinic in her village. All interviews and exams were completed
      in August 1998. RESULTS: Of the 289 QS patients interviewed (a follow-up rate of
      96.3%), 265 had had 2 insertions. There were 3 pregnancy failures for a
      cumulative life table failure rate of 1.2 per 100 women at 24 months. The 299 TL
      patients (a follow-up rate of 99.7%) had a similar rate of 0.7. There were no
      life-threatening side effects or deaths in either group. QS was less disruptive,
      more easily tolerated, required fewer resources and was viewed more favorably
      than TL by women and their spouses. CONCLUSIONS: Both methods were found safe and
      very effective. However, QS was considered to be more acceptable than TL.

PMID- 29645216
TI  - The acceptability, efficacy and safety of quinacrine non-surgical sterilization
      (QS), tubectomy and vasectomy in 5 provinces in the Red River Delta, Vietnam: a
      follow-up of 15,190 cases.
AB  - OBJECTIVES: To compare the safety, efficacy and acceptability of quinacrine
      sterilization (QS), tubectomy and vasectomy in Vietnam. METHODS: This study was
      initiated in January 1998 and completed in February 2000. A sample of 9 districts
      in 5 provinces, where the prevalence of QS was known to be high, was selected.
      Every person sterilized in these 9 districts between January 1, 1988 and March
      31, 1998 was identified and systematically interviewed by family planning
      clinicians who had received special training for this project. RESULTS: A total
      of 15,982 sterilization users were identified and 15,190 were interviewed and
      examined, including a gynecologic exam, if needed: a follow-up rate of 95%. Of
      those interviewed, 9,753 used tubectomy, 3,734 used QS and 1,703 used vasectomy.
      All three methods were found to be safe, although morbidity associated with
      tubectomy was more serious than with QS or vasectomy. No deaths were reported.
      After more than 5 years of follow-up, tubectomy had the lowest failure rate:
      1.0%, followed by 4.1% with vasectomy. A pregnancy rate of 13.2% was reported
      with quinacrine, although only a small fraction of these failures were confirmed.
      A strong preference for QS was found. CONCLUSION: QS has an important role to
      play in sterilization services in Vietnam.

PMID- 29645217
TI  - Quinacrine female nonsurgical sterilization (QS): endometrial assessment by
      vaginal ultrasonography in 128 women.
AB  - OBJECTIVE: Investigate effectiveness, safety and endometrial pattern after QS.
      METHOD: This study began in March 1999 and ended March 18, 2003; 128 women
      received transcervical insertions of quinacrine. Follow-up visits with ultrasound
      were scheduled at 1, 3, 6, 12-month intervals. RESULTS: Two pregnancies occurred,
      one at 25 months, the other at 37. Adverse events (AE) were: yellow vaginal
      discharge, headache, mild abdominal pain, vaginal pruritus, nausea and transient
      decrease in endometrial thickness. One patient had allergic reaction. A third
      insertion was done in case of vaginal bleeding (16.4%). One year after QS 10%
      still had amenorrhea, which may be the results of the fact that 73% of our
      patients had received DMPH. Once inside the uterus, the dissolved quinacrine
      could be seen within seconds, via ultrasound as a "Lake of Quinacrine" which
      stays for up to two hours. Frequently, a transverse vaginal ultrasonographic view
      of the uterine cavity showed plug-like echogenic points at the cornua.
      CONCLUSION: Quinacrine sterilization is safe and effective. The echogenic points
      need to be more thoroughly studied in order to affirm whether ultrasonography may
      identify the blockage of the tubes. Since early pregnancy is due to imperfect
      tubal closure, the use of ultrasound may prevent failure. However, pregnancy due
      to later recanalization cannot be avoided.

PMID- 29645218
TI  - Feasibility of recruiting publicly insured children with special health care
      needs for a population-based clinical study.
AB  - OBJECTIVE: Assess the feasibility of recruiting children with special health care
      needs (CSHCN) into a clinical study using Medicaid data. METHODS: We used the 3M
      Clinical Risk Grouping software to identify and classify Medicaid-enrolled CSHCN
      ages 7-17 years in Washington into one of three chronic condition severity
      groups: episodic, life-long, or malignancy/catastrophic. We compared contact,
      recruitment, enrollment, and data completion proportions across severity groups
      using the Pearson chi-square or Fisher's exact test. RESULTS: Of the 2,666 CSHSN
      in the Medicaid files, we contacted 922 and recruited 211 CSHCN (22.8 percent).
      One-hundred-thirteen made their study visit (53.6 percent) and 98 had complete
      data (86.7 percent). We contacted and recruited significantly larger proportions
      of CSHCN with malignancies/catastrophic conditions (P < 0.01). Across severity
      groups, there were no differences in enrollment (P = 0.27), but a smaller
      proportion of CSHCN with life-long conditions had complete data (P = 0.03).
      CONCLUSION: It is feasible to recruit CSHCN from Medicaid files for clinical
      studies.

PMID- 29645219
TI  - The GABAergic system as a therapeutic target for Alzheimer's disease.
AB  - Glutamatergic and cholinergic dysfunction are well-attested features of
      Alzheimer's disease (AD), progressing with other pathological indices of the
      disorder and exacerbating neuronal and network dysfunction. However, relatively
      little attention has been paid to the inhibitory component of the
      excitatory/inhibitory (E/I) network, particularly dysfunction in the gamma
      aminobutyric acid (GABA) signaling system. There is growing evidence in support
      of GABAergic remodeling in the AD brain, potentially beginning in early stages of
      disease pathogenesis, and this could thus be a valid molecular target for drug
      development and pharmacological therapies. Several GABAergic drugs have been
      tested for efficacy in attenuating or reversing various features and symptoms of
      AD, and this could represent a novel path by which we might address the growing
      need for more effective and benign therapies.

PMID- 29645220
TI  - Role of a symptom-based algorithmic approach to chronic pelvic pain.
AB  - OBJECTIVE: Chronic pelvic pain (CPP) is a disorder that has a significant impact
      on the patient's quality of life. Laparoscopic diagnosis can be disappointing,
      and recurrence is common after surgical treatment. A symptom-based algorithmic
      approach to treatment of CPP is presented that is safe and cost-effective.
      METHODS: This approach is oriented towards making a potential clinical diagnosis
      of endometriosis. It relies on a structured evaluation of the patient and
      administration of medical therapy including GnRH agonists to selected patients.
      Evaluation begins with a history and physical examination; selected cases receive
      specific therapy. Non-responders undergo appropriate laboratory and imaging
      studies. If results remain negative, it is possible to make a clinical diagnosis
      of endometriosis and begin empiric treatment. RESULTS: Early results strongly
      indicate that using this approach allowed clinicians to make highly accurate
      diagnoses (correct in 85-90% of cases). CONCLUSION: Use of this approach will
      minimize the need for surgery.

PMID- 29645221
TI  - Re-defining the focus in the management of chronic pelvic pain.

PMID- 29645223
TI  - A post-presentation discussion.

PMID- 29645222
TI  - An appraisal of the role of laparoscopy: past, present, and future.
AB  - OBJECTIVE: To review the role of laparoscopy in the management of chronic pelvic
      pain (CPP). METHOD: A literature search was conducted to obtain a clear
      perspective on the role of laparoscopy for CPP. RESULTS: Laparoscopy has been
      widely used as a diagnostic tool in CPP, but often falls short in defining the
      type and activity of ectopic endometrial-like tissue. Because pelvic
      endometriosis includes a wide range of lesions, histological confirmation varies
      greatly. The evaluation of peritoneal endometriosis at laparoscopy can be
      misleading. In one study 43% of the patients with minimal or mild endometriosis
      were found at second-look laparoscopy to be free of lesions. Finally, laparoscopy
      is not without major complications and the risk of undiagnosed bowel injury is
      likely to be underestimated. CONCLUSION: The diagnosis of endometriosis can no
      longer be limited to the visual inspection of the pelvis but requires a wider
      range of investigations to assess the reproductive system and the role of
      endometriotic lesions and adhesions in CPP.

PMID- 29645224
TI  - Focus for the future: tackling the 'pelvic pain' problem in gynecologic practice 
      an interactive session.
AB  - OBJECTIVE: The clinical management of women with chronic pelvic pain (CPP) and
      endometriosis involves important issues that exist at the interface between these
      two conditions. METHODS: To address these issues, an interactive session was
      convened to discuss an empiric algorithmic protocol for the clinical management
      of CPP and endometriosis presented during the Takeda-sponsored session as part of
      the XVI FIGO World Congress of Gynecology and Obstetrics and to monitor the
      audience response to this approach. RESULTS: Approximately one-third of the
      audience responded that they would definitely try this method, approximately 18%
      were already using it, and approximately 21% would be fairly likely to try it.
      Thirty percent of the audience was not convinced that the empiric approach is the
      best management strategy. CONCLUSION: The advantages of this management strategy
      should be carefully considered, and discussed with colleagues who do think it is
      the reasonable treatment approach in selected cases.

PMID- 29645225
TI  - Moving toward a new therapeutic model for chronic pelvic pain: a summary.

PMID- 29645226
TI  - Chronic pelvic pain: defining the scope of the problem.
AB  - OBJECTIVE: To define the scope of the problems associated with chronic pelvic
      pain (CPP) and optimize management. METHOD: Clinical trial results and healthcare
      utilization data from the literature were reviewed. RESULTS: Recent evidence
      suggests that a large percentage of women experience CPP. While no etiology tends
      to be found in the majority of these women, the annual cost for diagnosing and
      treating CPP seems considerable. The management of patients with negative
      laparoscopies constitutes a clinical challenge. While surgical and medical
      therapy have a role in CPP, there appears to be no 100% effective cure.
      CONCLUSIONS: There is no consensus on management of patients with no visible
      pathology and chronic pelvic pain. Physicians should select a treatment for CPP
      that will be the least complicated and least risky and will deliver speedy
      symptomatic relief.

PMID- 29645227
TI  - A dvances in understanding of molar pregnancy.

PMID- 29645228
TI  - Postmolar hCG surveillance programme, chemotherapy stratification in gestational
      trophoblastic disease.

PMID- 29645229
TI  - Biology of human trophoblast.
AB  - In order to elucidate the regulation of placental growth, we have characterized
      the expression of proliferating cell nuclear antigen (PCNA), apoptotic DNA
      fragmentation and bc1-2 protein in human placenta during pregnancy. PCNA and bc1
      2 protein expression were examined by immunohistochemical techniques, while the
      occurrence of apoptotic DNA fragmentation was assessed by in situ analysis of DNA
      3'-end labeling method. Both PCNA expression and apoptotic DNA fragmentation were
      found in cytotrophoblasts (C-cells), being most abundant in early placenta, less
      abundant in midterm placenta and least abundant in term placenta. In contrast,
      bc1-2 protein expression was found in syncytiotrophoblasts (S-cells), being least
      abundant in early placenta, less abundant in midterm placenta and most abundant
      in term placenta. These data indicate that early placenta is characterized by the
      highly proliferative activity of C-cells associated with the increased occurrence
      of apoptosis, whereas term placenta is characterized by the abundant expression
      of bc1-2 protein in S-cells. Furthermore, effects of EGF on the proliferative
      activity and differentiated function of trophoblasts were investigated using an
      organ culture system. Expiants of trophoblastic tissues were cultured with or
      without EGF, in the presence or absence of 10-8 M triiodo-L-thyronine (T3) in a
      serum-free condition. In 4-5 week placentas, EGF and EGF receptor were almost
      exclusively localized in C-cells, and EGF augmented the proliferative activity of
      C-cells without affecting the ability to secrete hCG and hPL. By contrast, in 6
      12 week placentas, EGF and EGF receptor were predominantly localized in S-cells,
      and EGF stimulated hCG and hPL secretion without affecting the proliferative
      activity of C-cess. The addition of T3 (10-8 M) resulted in an increased
      secretion of immunoreactive EGF by cultured placental explants. These findings
      suggest that EGF acts as a local factor in regulating early placental growth and
      function in synergy with thyroid hormone. On the other hand, progesterone
      selectively inhibited pleise hCG (alpha, beta) mRNAs expression and decreased hCG
      secretion in normal placental tissues, whereas choriocarcinoma did not respond to
      progesterone. This suggests that inhibitory regulation of hCG synthesis in
      choriocarcinoma is different from normal placenta. It was also found that in
      molar trophoblasts and choriocarcinoma cells PCNA expression was high, but both
      bc1-2 protein and apoptotic signal expression were low. Characterization of
      choriocarcinoma hCG revealed that there are striking differences in carbohydrate
      structures between normal hCG and choriocarcinoma hCG. Sialic acid content in
      choriocarcinoma hCG was extremely lower compared to that in normal hCG. The
      detection of the alteration in hCG sugar chains is useful for biochemical
      diagnosis of choriocarcinoma.

PMID- 29645230
TI  - The management of high-risk gestational trophoblastic tumours (GTT).
AB  - Between 1979 and 1995 we have treated 272 consecutive women with high-risk (GTT
      including 121 previously treated patients who were treated with the weekly EMA/CO
      (etoposide, methotrexate, actinomycin D alternating with cyclophosphamide and
      vincristine). The median follow-up is 4.5 years (range 1-16 years). The
      cumulative 5 year survival is 86.2% (95% confidence interval 81.9-90.5%). No
      deaths from GTT occurred later than 2 years after starting EMA/CO. In a
      multivariate analysis, adverse prognostic factors were the presence of liver
      metastases (p < 0.0001), interval from antecedent pregnancy > 24 months (p <
      0.0001), brain metastases (p = 0.0008) and term delivery of antecedent pregnancy
      (p = 0.045). There were 11 (4%) early deaths while 213 (78%) achieved complete
      remission. 47 (17%) developed drug resistance to EMA/CO of whom 33 (70%) were
      salvaged by further cisplatinum based chemotherapy and sugery. 2 women developed
      acute myeloid leukaemia after treatment with EMA/CO. 56% of women who have been
      in remission for at least 2 years and had fertility conserving surgery have
      achieved pregnancy since completing EMA/CO and there have been 112 live births
      including 3 babies with congenital abnormalities. EMA/CO is an effective, easy to
      administer and well tolerated regimen for treating patient with high-risk GTT.
      More than half of these women will retain their fertility. However, there is a
      small but significant increase in second malignancies.

PMID- 29645231
TI  - Molecular heterogeneity of hCG beta - related glycoproteins and the clinical
      relevance in trophoblastic and non-trophoblastic tumors.
AB  - We analyzed immunoreactive hCG/hCG beta (IR-beta) in the sera and urine of
      patients with trophoblastic diseases and non-trophoblastic tumors by using enzyme
      immunoassays (EIAs) specific for intact hCG, free hCG beta, and beta-core
      fragment of hCG (beta-CF). In trophoblastic diseases, while intact hCG and free
      hCG beta were contained in both serum and urine, the beta-CF could be detected
      only in the urine of the patients. The relative contribution of the beta-CF to
      the total urinary IR-beta accounted for about 30-50% in normal early pregnancy
      and hydatidiform mole, and more than 60% in choriocarcinoma. We conclude that
      intact hCG should be measured in the serum rather than in the urine as a tumor
      marker for trophoblastic dieseases, and suggested that the ratios of intact hCG,
      free hCG beta, and beta-CF to each other may be useful indices in the
      differential diagnosis of trophoblastic diseases. Ectopic IR-beta was also
      investigated in the sera and urine of the patients with cervical, endometrial,
      ovarian, lung, and bladder carcinomas. We found that even when IR-beta could not
      be detected in the serum, the urine of the same patients with cancer often
      contained the significant amounts of IR-beta. The chromatographic study indicated
      that these urinary IR-beta were essentially attributed to beta-CF, leading to the
      evaluation of urinary beta-CF as a tumor marker. The positive rated of urinary
      beta-CF were 48% for cervical, 38% for endometrial, and 84% for ovarian, 40% for
      lung, and 42% for bladder carcinomas. We conclude that ectopic production of hCG
      beta by non-trophoblastic tumors is not a rare phenomenon and it can be
      recognized as a tumor marker when beta-CF is measured in urine of the patients.

PMID- 29645232
TI  - Molecular genetic studiesin gestational trophoblastic diseases.

PMID- 29645233
TI  - Analysis of risk factors for postmolar trophoblastic disease: categorization of
      risk factors and effect of prophylactic chemotherapy.

PMID- 29645234
TI  - The management of gestational trophoblastic disease in developing countries such
      as malaysia.
AB  - Gestational trophablastic disease is a common gynaecological problem in Malaysia.
      The incidence of molar pregnancy is 2.8 per 1000 deliveries, being more common
      amongst the Chinese. The preferred method of evacuation is suction curettage;
      complete evacuation of the uterus was not achieved at the first attempt in 25 per
      cent of cases. Partial moles in our centre comprised 30 per cent of all moles.
      This is potentially malignant and needs follow-up for a complete mole. In the
      management of an invasive mole, chemotherapy should not be withheld in the
      presence of metastases and failure of regression of hCG. The role of prophylactic
      hysterectomy and prophylactic chemotherapy in the management of molar pregnancyis
      discussed "Selective preventive chemotherapy" in patients at "risk" appears
      appropriate. Chemotherapy remains the main modality of treatment for gestational
      trophoblastic tumours (GTT). We categorised our patients into low, medium and
      high-risk groups; survivals were 100, 98, and 61.7 percent respectively. These
      patients when categorised according to FIGO staging had survivals of 100, 80,
      78.6 and 68.2 per cent respectively for stages 1, 2, 3 and 4 respectively. The
      reasons for the poor suvival in the 'high-risk' group are discussed. Colour
      doppler blood flow studies are now being carried out; its role needs further
      evaluation. Surgery and radiotherapy have only a limited role in the management
      of these cases.

PMID- 29645235
TI  - Trophoblastic disease, genomic imprinting and DNA methylation.

PMID- 29645237
TI  - Production, structure, clinical detection and monitoring of hCG in trophoblast
      disease.

PMID- 29645236
TI  - Remission criteria for gestational trophoblastic dieases.

PMID- 29645238
TI  - Recent aspects of gestational trophoblastic disease in Japan.
AB  - The regional registration in 11 prefectures and one area covering 34% of total
      Japanese population started in 1974, increasing gradually to 21 prefectures and
      one area in 1993 covering 48.5% of total Japanese populations, by the Japan
      Trophoblastic Disease Committee under the auspices of Japan Society of Obstetrics
      and Gynecology. The results showed marked decreasing trend in incidence of molar
      pregnancy and choriocarcinoma in Japan. The most frequent antecedent pregnancies
      of choriocarcinoma has shifted from molar pregnancy in 1974 to term pregnancy in
      1993. The Choriocarcinoma Risk Score Table that is in use and of practical
      significance, differentiating choriocarcinoma from invasive or metastatic mole by
      reference to simple 8 clinical items with the probability of more than 90% when
      compared with the histological diagnoses, is also presented.

PMID- 29645239
TI  - The diagnosis and prognosis of molar pregnancy: The experience of the National
      Referral Centre in London.
AB  - Since 1973, hCG follow up and treatment of patients with hydatidiform moles in
      the UK has been centralised. Registrations of moles have increased from 475 to
      1248 in 2 years but histological review shows that first trimester non-molar
      hydropic abortions (HAs) and complete moles (CMs) are often called partial moles
      (PMs) by pathologists. The introduction and widespread acceptance of the term PM
      in 1977, coincided with improvements in ultrasound which brought forward 6 weeks
      the average time of evacuation of CMs, when hydrops is not yet complete but
      partial and when vessels are present in most CMs, leading to erroneous diagnoses
      of PM. Many true PMs are dismissed as HAs and often, HAs are called PMs. Valid
      diagnostic criteria for younger CMs and for PMs have been available for over 10
      years and when used, PM is overwhelmingly associated with triploidy. Reported
      diploid PMs are partly explained by misdiagnosed HAs, rare cases of Beckwith
      Widemann syndrome, CMs with partially developed hydrops, twin pregnancies and
      rare androgenetic CMs with fetal red cells in villi. A rare mole with "normal"
      diploid biparental karyotype probably exists but morphologically resembles CM. CM
      and PM have widely different prognosis but the present diagnostic confusion means
      much of the published epidemiological, clinical and genetic information on PM
      based on suspect diagnostic criteria ia also suspect.

PMID- 29645240
TI  - Trophoblastic disease: Twenty years' experience at Niigata University.
AB  - The author engaged in the registration work and the clinical studies of
      trophoblastic disease over 20 years at Niigata University in Niigata prefecture,
      before transferring to University of the Ryukyus in Okinawa prefecture in 1992.
      In this paper, the following four topics are reviewed and discussed. 1) the
      registration data of trophoblastic disease in Niigata prefecture, 2) the
      treatment results of gestational chorio-carcinoma at the Niigata University
      Hospital, 3) a trial administration of Gn-RH analogue in patients with
      gestational choriocarcinoma to suppress secretion of hCG-like substance (hLS)
      which might cross-react anti-hCG antibodies in hCG immunoassay system, 4) the two
      rare cases of extrauterine gestational choriocarcinoma who were presented to the
      Ryukyu University Hospistal.

PMID- 29645241
TI  - The classification of gestational trophoblastic disease: a critical review.
AB  - Gestational trophoblastic disease defines a group of conditions which arises from
      the fetal chorion. Two of the most important advances in the management of
      gestational trophoblastic disease have been the standardisation of terminology,
      and the concept of risk assignment based on classification or staging systems
      which allows rationalisation of treatment. Gestational trophoblastic disease is
      unique as the prognosis is dependent not only on the anatomic extent but also the
      presence of prognostic factors. A staging system similar to that used for other
      cancers does not apply to this disease because in most cases diagnosis is bases
      not on histology but on clinical or biochemical parameters. Metastatic spread to
      distant organs can occur early, even in the absence of disease in the uterus or
      pelvis. Staging in gestational trophoblastic disease must include prognostic
      factors in addition to anatomic extent of disease. Broadly there are two
      categories of classification in current use. The first is based on the usual
      staging system as in other cancers, with four stages of disease, but at the same
      time prognostic factors are incorporated. This has the important advantages of
      simplicity and uniformity with other staging systems. However the main pitfall is
      that no recommendations are made for treatment. The other broad category consists
      of risk tables, based on anatomic spread as well as prognostic factors. Here
      patients are assigned varying risk scores, with guidelines for multiagent
      chemotherapy at the outset in high-risk patients to minimise drug resistant
      disease. The ideal system would be one which has four stages of disease, so that
      comparison is easier, with recommendations for combination chemotherapy beyond a
      certain stage of disease.

PMID- 29645243
TI  - Do imaging techniques, grey scale ultrasound, color doppler flow ultrasound and
      magnetic resonance imaging provide clinically useful information during the
      therapy of nonmetastatic gestational trophoblastic neoplasia.

PMID- 29645242
TI  - Changing face of gestational trophoblastic tumor.
AB  - During the years there have been many advances in the diagnosis and treatment of
      gestational trophoblastic tumor (GTT) with marked improvement in the outcome. At
      the same time in Korea there have been many social and economic changes which
      also have had a marked influence on the outcome. The purpose of this study was to
      review the changes that have occured among patients admitted to Il Sin Christian
      Hospital, Pusan, Korea over the past four dccades.

PMID- 29645244
TI  - Gestational trophoblastic disease in Vietnam prevalence, clinical features,
      management.

PMID- 29645245
TI  - Management of GTD patients with high-risk site metastases.

PMID- 29645246
TI  - IL-6 antisense oligonucleotides inhibit the growth of choriocarcinoma cells in
      vitro: a possible intracellular autocrine growth mechanism mediated by IL-6.

PMID- 29645247
TI  - Effects of multiagent chemotherapy and independent risk factors in the treatment
      of high-risk GTT -25 years experiences of KRI-TRD.
AB  - : A retrospective and comparative study of high-risk gestational trophoblastic
      tumor (GTT) treated with different chemoregimen from 1971 to 1995 was performed
      and to find most effective chemotherapy regimen and independent risk factors.
      Three hundred seven patients in scoring over 8 points in WHO classification were
      categorized into high-risk group among 802 GTT cases received chemotherapy in the
      2,418 GTD patients registered at KRI-TRD (Korean Research Institute for
      Gestational Trophoblastic Disease), Catholic University Medical College in Korea.
      Study groups of multiagent combination chemotherapy in 227 patients of the high
      risk GTT were divided such as 49 cases of combination chemotherapy with MTX +
      folinic acid and Act-D, 40 cases of MAC regimen, 42 cases of CHAMOCA regimen, and
      96 cases of EMA/CO. Initial tumor response according to hCG titer decrease was
      found in good response (log fall) 69.8%, of EMA /CO regimen group. On the other
      hand, good response was shown in only 24.5% of MTX + ACT-D, 32.5% of MAC regimen,
      and 52.4%, of CHAMOCA regimen respectively. Remission rate of EMA/CO regimen was
      90.6% (87/96) and courses of chemotherapy until remission was 8.5 +/- 2.2.
      However, remission rate of other regimens of MTX + Act-D, MAC, and CHAMOCA were
      63.3%, (31/49) 67.5% (27/40) and 76.2% (32/45) respectively, with 10.0 +/- 4.0,
      10.7 +/- 4.3, 9.1 +/- 3.9 chemotherapy courses respectively until remission.
      Therefore, EMA/CO regimen groups were found to have low drug toxicity, early
      remission and a low failure rate. In the study of independent risk factors in the
      165 cases of high-risk gestational trophoblastic tumor patients received EMA/CO
      regimen, stepwise Coxs proportional hazard's regression of prognostic factors
      using multivariate analysis revealed tumor age, number of metastatic organs,
      metastatic site and inadequate previous chemotherapy. According to the
      performance of fitted logistic regression model, the prediction rate of death and
      survival was 80.5%. CONCLUSIONS: The most effective chemotherapy to high-risk GTT
      was EMA/CO regimen than other regimens. The following factors showed poor
      prognosis; 1) Tumor age is over 12 month, 2) more than 2 organs had metastatic
      lesion, 3) inadequate previous therapy that includes unplanned operation and
      inadequate previous chemotherapy.

PMID- 29645248
TI  - Past, present and future of gestational trophoblastic diseases.

PMID- 29645250
TI  - Second line chemotherapy in gestational trophoblastic disease (GTD).

PMID- 29645249
TI  - Cell proliferation and hCG secretion in human choriocarcinoma treated withmtx and
      it's insulin enhances.

PMID- 29645251
TI  - Invasive moles and choriocarcinoma: origins and nature.

PMID- 29645252
TI  - Tumor markers in the management of GTD.

PMID- 29645253
TI  - Metastatic placental site trophoblastic tumor.
AB  - Since our publication, which first defined the malignant potential of placental
      site trophoblastic tumor (PSTT), we have had a keen interest in this rare, unique
      entity. This histologic entity is noted by its monomorphic population of
      trophoblast-like cells which are classified as originating in the intermediate
      trophoblast. These cells contain hymman placental lactogen (HPL). This is in
      contrast to cytotrophoblastic and syncytiotrophblastic tissues as the histologic,
      cytologic and immunohistochemical stain characteristics are disparate. Its rarity
      and the wide spectrum of clinical behavior combined with the lack of sensitivity
      of serum levels of beta hCG in predicting disease recurrence and spread have lead
      to anecdotal reports outlining clinical management. Most discerning to the
      clinician is the high mortality of metastatic placental site trophoblastic tumor.
      At our institution, we have treated two patients with a metastatic disease with a
      successful conclusion. The durability of responses is 3 and 8 years. This report
      will present these patients in detail and define the important characteristics of
      successful treatment. The use of dose-intensive, multi-agent chemotherapy, early
      intervention when metastatic disease is discovered, imaging techniques to define
      disease spread, surgery for localized disease and the use of growth factors, most
      notably granulocyte colony-stimulating factor (G-CSF), are the fundamentals of
      clinical care of placental site trophoblastic tumor in patients with metastatic
      placental site trophoblastic tumor.

PMID- 29645255
TI  - Immunobiological and neoplastic dimensions of the trophoblast.

PMID- 29645254
TI  - Epidemiology and time trends of gestational trophoblastic disease in Korea.
AB  - OBJECTIVES: For the purpose of determining the annual incidence and time trends
      of gestational trophoblastic disease (GTD), the medical records from 24
      university hospitals, 13 private general hospitals and the Korean Research
      Institute of Gestational Trophoblastic Disease (KRI-TRD) were analyzed from 1971
      to 1995. MATERIALS & RESULTS: From a total of 7198 GTD cases (H-mole = 3831,
      Invasive mole = 2163, Choriocarcinoma = 1177, PSTT = 27) among 838659 deliveries
      between 1971 and 1995, the hospital-based incidence of H-mole per 1000 deliveries
      declined from 40.2 during 1971-975, to 2.3 during 1991-995. The population-based
      incidence of H-mole, hwoever, revealed an average of 2.05 per 1000 deliveries
      during 1991-995. Old age and gravidities as factors in GTD patients both
      decreased significantly during the study period. Time trends for the incidence of
      GTD in Korea revealed significant changes, not only a decrease in the incidence
      of GTD, but also an improvement in the annual remission rate. Korea's socio
      eonomic improvement in recent decades also contributed to the decreased incidence
      of GTD and the increased survival rates.

PMID- 29645256
TI  - Forty-five year's experience of the treatment of choriocarcinoma and invasive
      mole.
AB  - Our work was begun in 1949, through many yera's effort, several chemicals (such
      as 6 MP, 5 FU and others) were found to be effective for the treatment of
      choriocarcinoma (C.C.) and invasive mole (I.M.). From 1959 through 1985, 1500
      patients were consecutively treated. The mortality rate of CC was reduced from >
      90% to < 20%. No more death occurred in IM. All Survivors followed up for 10-38
      years showed no evidence of residual disease. 80% of the young patients treated
      with chemotherapy alone conceived after recovery. The pregnancy outcome showed no
      deviation from that of the general population. All children are growing up
      normally many married and gave birth to normal third generations. The results
      indicated that chemotherapy with 5 FU achieves not only a complete remission, but
      also a cure, even with wide-spread metastases. The results of choriocarinoma and
      invasive mole treated with mainly 5 FU were reported. The clinical experience in
      the management of metastases at different sites were also summarized.

PMID- 29645258
TI  - Therapeutic protocols for FIGO Stages of GTD.

PMID- 29645257
TI  - Gestational trophoblastic diseases in mongolia.

PMID- 29645259
TI  - Involvement of IGF2 and H19 imprinting in choriocarcinoma development.
AB  - Complete hydatidiform mole is an abnormal pregnancy characterized by grossly
      swollen villi in the absence of a fetus (Kajii and Ohama 1997, Wake et al., 1978,
      Jacobs et al., 1980). It is well known that this abnormal pregnancy product is
      androgenetic in origin. The entire genome of the molar conceptus is paternally
      derived. The majority of moles result from fertilization of an empty egg by
      haploid sperm. The paternally derived haploid set then duplicated without
      cytokinesis and restores diploidy. Invariably, this class of moles has a 46, XX
      karyotype and is completely homozygous for genetic markers. Fertilization of an
      empty egg by two sperms is responsible for the remaining case. These moles show a
      mixture of homozygous and heterozygous patterns of paternally derived genetic
      markers. Although complete mole is usually a benign process, 10 to 20 percent of
      cases leads to either invasive mole or choriocarcinoma. This propensity to
      malignancy has to associate with the genetic features shown in the mole, that
      imply the formation of homozygosity and the selective inheritance of paternal
      genome. It has been described in various human malignancies that both genetic
      features associate with the inactivation of tumor suppressor genes. Homozygosity
      would lead to the inactivation of tumor suppressor gene in the mole by a signal
      event occurred on sperm DNAs. In turn, paternal transmission would result in the
      silencing of particular tumor suppressor genes. Thus, tumor suppressor genes
      inactivated either by homozygosity formation or by paternal transmission would be
      involved in the pathogenesis of choriocarcinoma. Both the maternal and paternal
      genomes are necessary for normal embryonic development in mammals. Parental
      origin-specific functional differences between two alleles, known as genomic
      imprinting, seem to be exploited for a regulatory mechanism crucial for the
      proper development of both embryonic and extraembryonic tissues. The list of
      imprinted genes identified is growing rapidly lately in mouse and man (DeChiara
      TM et al., 1991, Barlow et al., 1991, Bartolomei MS et al., 1991, Leff SE et al.,
      1992, Hatada I et al., 1993, Giddings SJ et al., 1994, Hayashizaki Y et al.,
      1994, Villar AJ et al., 1994, Guillemot F et al., 1995). Among these, IGF2 and
      H19 tightly linked on human chromosome 11 are of special interest because of
      their reciprocal imprinting and possible association with certain malignancy and
      congenital abnormalies. The IGF2 gene expressed from the paternally derived
      allele (Ohlsson et al., 1993, Giannoukalis et al., 1993), whereas the H19 gene is
      expressed from the maternally derived allele (Rachmilewitz et al., 1992, Zhang et
      al 1993, Ferguson-Smith et al., 1993).

PMID- 29645261
TI  - Determinants of quality of life among people diagnosed with schizophrenia at
      outpatient clinics.
AB  - PURPOSE: The study examines the determinants of the quality of life (QoL) among
      outpatients with schizophrenia in Jordan. DESIGN AND METHODS: A cross-sectional
      study design was used with 157 people with schizophrenia treated in outpatient
      clinics. Demographic, clinical and psychosocial variables were examined for their
      influence on QoL. Data were analysed with descriptive statistics, Pearson product
      moment correlation and stepwise forward multiple linear regression. FINDINGS: The
      majority of the study participants were female, single, unemployed, had secondary
      level of education or less and were being supported financially by family
      members. QoL correlated negatively with advanced age, male gender, longer
      duration of illness, high body mass index and prescribed typical anti-psychotic
      medication. However, it was correlated positively with employment and being
      married. Illness duration, recurrent hospitalisation, knowledge level about
      schizophrenia, psychiatric symptoms and coping mechanisms were found to be key
      significant predictors of QoL among participants. PRACTICAL IMPLICATIONS: The
      study findings enhance our understanding of socio-demographic, clinical and
      psychosocial characteristics influencing the QoL in people with schizophrenia.
      Involvement of families in the management process may improve patients' ability
      to be integrated in the community and be more socially active.

PMID- 29645260
TI  - Gene, interaction, signal generation, signal divergence and signal transduction
      of the LH/CG receptor.
AB  - Trophoblastic neoplasms and choriocarcinoma cells express high levels of the hCG
      receptor. The hCG receptor is encoded by a single gene in chromosome 2p21-p16,
      spanning over -70 kb with 11 exons and 10 introns. Multiple mRNA species are
      produced from the gene utilizing two proximal promoters and several Sp-1 elements
      as well as proximal and distal suppressors. In fact, regulatory proteins which
      bind to one of these suppressors are expressed less in choriocarcinoma cell lines
      than in placenta. The LH/CG receptor is comprised of two structurally and
      functionally distinct domains, extracellular N-terminal exodomain and membrane
      embedded endodomain. These two domains can separately be expressed and processed,
      including folding. The exodomain alone has the high affinity hormone binding site
      but is not capable of generating hormonal signal. In contrast, the endodomain
      alone has the site for receptor activation. These two domains contact each other
      in holo-receptor and split receptor. This interaction, particularly through
      exoloops 2 and 3, constrains the high affinity hormone binding at the exodomain.
      Conversely, the exodomain could be involved in receptor activation. Therefore,
      these two domains are not entirely independent although they can be independently
      synthesized and processed. The existing envidence indicate that hCG and the
      receptor undergo multiple stages of interactions leading to receptor activation.
      Initial high affinity binding of hCG to the exodomain results into conformational
      adjustments of the hCG/exodomain complex. This leads to the secondary, low
      affinity contact of the hCG/exodomain complex with the endodomain. This secondary
      contact is responsible for generating signals. They are transduced through TM to
      the cytoplasmic portion (cytoloops and the C-terminal tail) of the receptor and
      then, transferred to cytoplasmic signaling molecules, such as G protein.
      Mutations in the exodomain and endodomain (N-extension, exoloops, TM, cytoloops,
      and cytoplasmic tail) have the potential to interfere with receptor activation at
      different steps, signal generation, transduction and transfer. Binding of hCG to
      the LH/CG receptor are known to induce two signals, one for adenylyl cyclase/
      cAMP and the other for phospholipase C/inositol phosphate/diacylglycerol. The
      cAMP signal and IP signal diverge at the surface of the receptor. These
      independent signals are separately transduced through the transmembrane domains
      to the cytoplasmic part of the receptor, indicating the existence of the distinct
      transducers for each of the signals. Furthermore, it is likely that the divergent
      signals are separately transferred to cytoplasmic signal molecules such as G
      protein. In addition, each of the cAMP signal and IP signal consists of at least
      three separate subsignals: affinity signal, maximal production (efficacy) signal
      and basal level signal. In heterodimeric hCG, there are distinct parts
      responsible for high affinity receptor binding and receptor activation.
      Particularly, the C-terminal reduces of the alpha subunit play a crucial role in
      receptor activation. This alpha subunit is shared with other glycoprotein
      hormones, follicle stimulating hormone and thyroid stimulating hormone.
      Interesting, the alpha C-terminal residues play distinct roles in all three
      hormones, despite its common nature.

PMID- 29645262
TI  - New reasons and new ways to study birth physiology.
AB  - The age of cesarean sections on request, epidurals and drips of oxytocin is a
      turning point in the history of childbirth. Until recently women could not give
      birth without releasing a complex cocktail of 'love hormones'. Today, in many
      countries, most women have babies without releasing these specific hormones. The
      questions must be raised in terms of civilization. This turning point occurs at
      the very time when several scientific disciplines suggest that the way human
      beings are born has long-term consequences, particularly in terms of sociability,
      aggressiveness or, in other words, 'capacity to love'. I find it relevant to
      combine data provided by perspectives as diverse as ethology, animal experiments,
      studies of the behavioral effects of hormones that fluctuate in the perinatal
      period, and a branch of epidemiology I call 'Primal Health Research'. This
      combination of data offers new reasons to disturb the physiological processes as
      little as possible. We are also at a time when a physiological approach can help
      to rediscover the basic needs of women in labor. These women firstly need to be
      protected against any sort of neocortical stimulation. We must keep in mind what
      the main stimuli of neocortical activity are: language, bright lights, the
      'feeling of being observed' and situations associated with a release of
      catecholamines.

PMID- 29645263
TI  - Human resources for maternity care: the present system in Brazil, Japan, North
      America, Western Europe and New Zealand.
AB  - This article describes the nature of the humanization of birth and the
      overlapping but distinct role of professionals within the maternity services with
      an emphasis on the role of the midwife. It describes the status of midwives in
      different parts of the world, and the common characteristics of work undertaken
      to restore the role of the midwife. Midwifery is seen as an essential component
      of effective maternity services. In addition it is important to recognize the
      important role that traditional birth attendants play in many parts of the world.
      An appropriate structure including primary and secondary and tertiary care
      services are important for professionals to play their full part.

PMID- 29645264
TI  - Forewords of the International Conference on the Humanization of Childbirth held
      on 2-4 November 2000, in Fortaleza, Ceara, Brazil.

PMID- 29645265
TI  - The technocratic, humanistic, and holistic paradigms of childbirth.
AB  - This article describes three paradigms of health care that heavily influence
      contemporary childbirth, most particularly in the west, but increasingly around
      the world: the technocratic, humanistic, and holistic models of medicine. These
      models differ fundamentally in their definitions of the body and its relationship
      to the mind, and thus in the health care approaches they charter. The
      technocratic model stresses mind-body separation and sees the body as a machine;
      the humanistic model emphasizes mind-body connection and defines the body as an
      organism; the holistic model insists on the oneness of body, mind, and spirit and
      defines the body as an energy field in constant interaction with other energy
      fields. Based on many years of research into contemporary childbirth, most
      especially through interviews with physicians, midwives, nurses, and mothers,
      this article seeks to describe the 12 tenets of each paradigm as they apply to
      contemporary obstetrical and health care, and to point out their futuristic
      implications. I suggest that practitioners who combine elements of all three
      paradigms have a unique opportunity to create the most effective obstetrical
      system ever known.

PMID- 29645266
TI  - From 'culture of dehumanization of childbirth' to 'childbirth as a transformative
      experience': changes in five municipalities in north-east Brazil.
AB  - Brazil has become a country known as having one of the most extreme examples of
      the consequences of the hospital-based medicalization of delivery care, while a
      model of humanization of birth was developed in the State of Ceara in the 1970s.
      The Government of Japan, through the Japanese International Cooperation Agency
      (JICA), collaborated with the Federal Ministry of Health of Brazil and the
      Government of the State of Ceara, in implementing the Maternal and Child Health
      Improvement Project in north-east Brazil (1996-2001). This project focused on
      'humanization of childbirth', with training based intervention activities.
      Behavioral changes among health professionals who received the project's
      participatory type of training were described using rapid anthropological
      assessment procedure (RAP) survey results. Changes from 'a culture of
      dehumanization of childbirth' to 'childbirth as a transformative experience' were
      observed.

PMID- 29645267
TI  - The humanization of birth experience at the University of Santa Catarina
      maternity hospital.
AB  - The Federal University of Santa Catarina (FUSC) Maternity Hospital (UH) initiated
      its activities on October 24, 1995, after several years of interdisciplinary
      committee work. The Committee based its work on the principles of humanization
      and interdisciplinarity. In this report we describe the process by which these
      services were implemented in this hospital, emphasizing the difficulties and
      possibilities of such an interdisciplinary project, the philosophical principles
      which guided the process, the work being carried out and the opinion of the
      clients on the care that they received. The work carried out at the UH generated
      a number of changes in the care and teaching of obstetrics at different
      professional levels. The maintenance of the basic principals of this work has,
      however, proved to be a continuous challenge with a constant struggle to ensure
      that the philosophy is adhered to by professionals and students, which strongly
      depends upon a continual educational process.

PMID- 29645268
TI  - The humanization of birth.
AB  - The humanization of birth conference drew more than 2000 people from 26
      countries. This article summarizes the conference. In much of the world women
      have learned to fear birth; this fear is represented by the increase in cesarean
      section rates seen in many countries. The humanization of birth may reduce this
      fear. Yet humanization is difficult to achieve in technocratic societies. It is
      important to recognize that safety and self-fulfilling experiences are not
      contradictions, and that humanized birth is the safest approach.

PMID- 29645269
TI  - The opinion of Brazilian women regarding vaginal labor and cesarean section.
AB  - OBJECTIVES: The opinions of Brazilian women regarding vaginal delivery and
      cesarean sections was studied. METHODS: Six hundred and fifty-six women who had
      given birth in seven hospitals in Sao Paulo and Pernambuco, using the Public
      Health Service, were interviewed. The opinions of women who had delivered only by
      cesarean section was compared with those of women who had had at least one
      vaginal delivery. RESULTS: Significantly more women who had experienced at least
      one vaginal delivery considered this to be the best way of giving birth (90.4%
      vs. 75.9% among C-section-only women). Similar proportions in both groups (45.5%
      and 42.8%) stated that vaginal labor is better because it causes less pain and
      suffering for the woman. Significantly more women who had experienced a vaginal
      labor (47.1% vs. 30.3%) reported that it had no disadvantage. More women who had
      only had cesarean sections referred not having contractions/pain as an advantage
      of this method (56.7% vs. 41.7%). CONCLUSIONS: Apparently, pain and women's
      perception of pain were the characteristics which differentiated women with
      history of vaginal delivery from those with cesarean sections in the sample
      studied. However, the opinion that vaginal delivery is better than cesarean
      section was expressed independently of the recognition that pain could be its
      main disadvantage.

PMID- 29645270
TI  - Conference agreement on the definition of humanization and humanized care.

PMID- 29645271
TI  - Fish can't see water: the need to humanize birth.
AB  - Humanized birth puts the woman in the center and in control, focuses on community
      based primary maternity care with midwives, nurses and doctors working together
      in harmony as equals, and has evidence based services. Western, medicalized, high
      tech maternity care under obstetric control usually dehumanizes, often leads to
      unnecessary, costly, dangerous, invasive obstetric interventions and should never
      be exported to developing countries. Midwives and planned out-of-hospital births
      are perfectly safe for low-risk births.

PMID- 29645272
TI  - The gap between evidence and practice in maternal healthcare.
AB  - The expected improvement in maternal and perinatal health in developing countries
      has not yet materialized. In addition to the factors related to socioeconomic
      conditions, we have identified areas where large gaps between evidence and
      practice are apparent. These gaps are in clinical care, implementation of
      effective practices and in selecting research priorities. We present examples
      from our own research and the literature to illustrate these points.

PMID- 29645273
TI  - Probing under pressure: a look inside the compartmental haemodynamics of skeletal
      muscle during rest and contraction.

PMID- 29645274
TI  - Effects of Maillard reaction products in a glucose-glycine alcoholic solution on
      antioxidative and antimutagenic activities.
AB  - BACKGROUND: Marinating meat with alcohol, such as wine and beer, is a common
      culinary practice in cultures worldwide. In this study we use a model marination
      solution comprising 0.2  mol L-1 glucose-0.2  mol L-1 glycine buffered to pH 4.3
      containing either 0 or 50% ethanol and mimicked the cooking process by heating
      for 12 h. Antioxidative and antimutagenic characteristics of Maillard reaction
      products (MRPs) were investigated. Reducing power, antioxidant activity (ferrous
      ion chelating ability), and free radical neutralization ability generated from
      1,1-diphenyl-2-pichrylhydrazyl and 2,2'-azino-bis(3-ethylbenzthiazoline-6
      sulfonic acid) were determined. Ames testing was performed. RESULTS: Results
      indicate that MRPs from aqueous and alcoholic solution exhibit four antioxidative
      assays in a dose-dependent manner from 0.16 to 10.00 mg mL-1 . However, MRPs from
      the alcoholic model were superior. In Ames testing, MRPs from both models are
      neither toxic nor mutagenic at the test concentrations of 0.63-10.00 mg/plate.
      However, MRPs from the alcoholic model exhibited a higher inhibitory effect on
      the direct-acting mutagen 4-nitroquinoline-N-oxide compared with the aqueous
      model. This result is consistent with the observation that MRPs with higher
      antioxidative capacity exhibit superior antimutagenic activity, suggesting that
      there are more different products in the alcoholic model. CONCLUSION: Our results
      add to the current knowledge about the antioxidative and antimutagenic properties
      of MRPs arising when food is cooked in the presence of ethanol. (c) 2018 Society
      of Chemical Industry.

PMID- 29645276
TI  - Arabidopsis ANGUSTIFOLIA3 (AN3) is associated with the promoter of CONSTITUTIVE
      PHOTOMORPHOGENIC1 (COP1) to regulate light-mediated stomatal development.
AB  - Light signals are perceived by multiple photoreceptors that converge to suppress
      the RING E3 ubiquitin ligase CONSTITUTIVE PHOTOMORPHOGENIC1 (COP1) for the
      regulation of stomatal development. Thus, COP1 is a point of integration between
      light signaling and stomatal patterning. However, how light signaling is
      collected into COP1 for the production and spacing of stomata is still unknown.
      Here, we report that the loss-of-function mutant of ANGUSTIFOLIA3 (AN3) delays
      asymmetric cell division, which leads to decreased stomatal index. Furthermore,
      overexpression of AN3 accelerates asymmetric cell division, which results in
      clusters of stomata. In addition, the stomatal development through AN3 regulation
      is mediated by light signaling. Finally, we find that an3 is a light-signaling
      mutant, and that AN3 protein is light regulated. Self-activation by AN3
      contributes to the control of AN3 expression. Thus, AN3 is a point of collection
      between light signaling and stomatal patterning. Target-gene analysis indicates
      that AN3 is associated with COP1 promoter for the regulation of light-controlling
      stomatal development. Together, these components for regulating stomatal
      development form an AN3-COP1-E3 ubiquitin ligase complex, allowing the
      integration of light signaling into the production and spacing of stomata.

PMID- 29645277
TI  - Insights to plant-microbe interactions provide opportunities to improve
      resistance breeding against root diseases in grain legumes.
AB  - Root and foot diseases severely impede grain legume cultivation worldwide.
      Breeding lines with resistance against individual pathogens exist, but these
      resistances are often overcome by the interaction of multiple pathogens in field
      situations. Novel tools allow to decipher plant-microbiome interactions in
      unprecedented detail and provide insights into resistance mechanisms that
      consider both simultaneous attacks of various pathogens and the interplay with
      beneficial microbes. Although it has become clear that plant-associated microbes
      play a key role in plant health, a systematic picture of how and to what extent
      plants can shape their own detrimental or beneficial microbiome remains to be
      drawn. There is increasing evidence for the existence of genetic variation in the
      regulation of plant-microbe interactions that can be exploited by plant breeders.
      We propose to consider the entire plant holobiont in resistance breeding
      strategies in order to unravel hidden parts of complex defence mechanisms. This
      review summarizes (a) the current knowledge of resistance against soil-borne
      pathogens in grain legumes, (b) evidence for genetic variation for rhizosphere
      related traits, (c) the role of root exudation in microbe-mediated disease
      resistance and elaborates (d) how these traits can be incorporated in resistance
      breeding programmes.

PMID- 29645275
TI  - Central and peripheral chemoreceptors in sudden infant death syndrome.
AB  - The pathogenesis of sudden infant death syndrome (SIDS) has been ascribed to an
      underlying biological vulnerability to stressors during a critical period of
      development. This paper reviews the main data in the literature supporting the
      role of central (e.g. retrotrapezoid nucleus, serotoninergic raphe nuclei, locus
      coeruleus, orexinergic neurons, ventral medullary surface, solitary tract
      nucleus) and peripheral (e.g. carotid body) chemoreceptors in the pathogenesis of
      SIDS. Clinical and experimental studies indicate that central and peripheral
      chemoreceptors undergo critical development during the initial postnatal period,
      consistent with the age range of SIDS (<1 year). Most of the risk factors for
      SIDS (gender, genetic factors, prematurity, hypoxic/hyperoxic stimuli,
      inflammation, perinatal exposure to cigarette smoke and/or substance abuse) may
      structurally and functionally affect the developmental plasticity of central and
      peripheral chemoreceptors, strongly suggesting the involvement of these
      structures in the pathogenesis of SIDS. Morphometric and neurochemical changes
      have been found in the carotid body and brainstem respiratory chemoreceptors of
      SIDS victims, together with functional signs of chemoreception impairment in some
      clinical studies. However, the methodological problems of SIDS research will have
      to be addressed in the future, requiring large and highly standardized case
      series. Up-to-date autopsy protocols should be produced, involving substantial,
      and exhaustive sampling of all potentially involved structures (including
      peripheral arterial chemoreceptors). Morphometric approaches should include
      unbiased stereological methods with three-dimensional probes. Prospective
      clinical studies addressing functional tests and risk factors (including genetic
      traits) would probably be the gold standard, allowing markers of intrinsic or
      acquired vulnerability to be properly identified.

PMID- 29645278
TI  - An Evaluation of the Pharmacodynamics, Safety, and Tolerability of the Potassium
      Binder RDX7675.
AB  - Hyperkalemia is common in patients with heart failure or chronic kidney disease,
      particularly those taking renin-angiotensin-aldosterone system inhibitors, and
      can cause arrhythmias and sudden cardiac death. The most widely used treatment,
      sodium polystyrene sulfonate (SPS), limits gastrointestinal potassium absorption,
      but has poor palatability. RDX7675 (RDX227675) is the calcium salt of a
      reengineered polystyrene sulfonate-based resin with improved palatability over
      SPS. The pharmacodynamic effects and safety of RDX7675 were assessed in a phase
      1, single-center, randomized, active-controlled study. Healthy volunteers
      received nominal active doses of RDX7675 4.6 g twice a day (BID), 4.6 g 3 times a
      day (TID), 6.9 g BID, 13.7 g daily (QD), 9.2 g TID, or 13.7 g BID (n = 12 each),
      or equivalent doses of SPS (n = 3 each), for 4 days. RDX7675 dosing increased
      stool potassium excretion and decreased urinary potassium excretion from
      baseline. Stool potassium excretion increased by up to 1481 mg/day with RDX7675
      (6.9 g BID), and urinary potassium excretion decreased by up to 939 mg/day (13.7
      g BID). Similar levels of potassium excretion were observed using QD, BID, or TID
      dosing of a 13.7 g total daily RDX7675 dose. Few adverse events were reported. In
      conclusion, repeated oral dosing with RDX7675 over 4 days reduced potassium
      absorption in healthy volunteers; the results support QD dosing of RDX7675 in
      future clinical studies.

PMID- 29645279
TI  - Block-matching sparsity regularization-based image reconstruction for low-dose
      computed tomography.
AB  - PURPOSE: Low-dose computed tomography (CT) imaging has been widely explored
      because it can reduce the radiation risk to human bodies. This presents
      challenges in improving the image quality because low radiation dose with reduced
      tube current and pulse duration introduces severe noise. In this study, we
      investigate block-matching sparsity regularization (BMSR) and devise an
      optimization problem for low-dose image reconstruction. METHOD: The objective
      function of the program is built by combining the sparse coding of BMSR and
      analysis error, which is subject to physical data measurement. A practical
      reconstruction algorithm using hard thresholding and projection-onto-convex-set
      for fast and stable performance is developed. An efficient scheme for the choices
      of regularization parameters is analyzed and designed. RESULTS: In the
      experiments, the proposed method is compared with a conventional edge
      preservation method and adaptive dictionary-based iterative reconstruction.
      Experiments with clinical images and real CT data indicate that the obtained
      results show promising capabilities in noise suppression and edge preservation
      compared with the competing methods. CONCLUSIONS: A block-matching-based
      reconstruction method for low-dose CT is proposed. Improvements in image quality
      are verified by quantitative metrics and visual comparisons, thereby indicating
      the potential of the proposed method for real-life applications.

PMID- 29645280
TI  - Effect of Vemurafenib on the Pharmacokinetics of a Single Dose of Digoxin in
      Patients With BRAFV600 Mutation-Positive Metastatic Malignancy.
AB  - The primary objective of this phase 1, open-label, multicenter, 3-period, fixed
      sequence study was to evaluate the effect of multiple doses of vemurafenib on the
      pharmacokinetics of a single dose of digoxin, a probe P-glycoprotein (P-gp)
      substrate, in patients with BRAFV600 mutation-positive metastatic malignancy.
      Following a 28-day screening period, patients received a single oral dose of
      digoxin 0.25 mg on day 1 in period A, oral vemurafenib 960 mg twice daily for 21
      days in period B (days 8-28), and a single oral dose of digoxin 0.25 mg on day 29
      and vemurafenib 960 mg twice a day for 7 days (days 29-35) in period C. Log
      transformed area under the concentration-time curve and peak concentration values
      for digoxin were compared between periods A (digoxin alone) and C (digoxin +
      vemurafenib) using an analysis of variance model. Twenty-six patients were
      evaluated for the primary pharmacokinetic analysis. The geometric mean ratio
      (period C/period A) of area under the curve to the last measurable concentration
      for digoxin was 1.82 (90%CI 1.63 to 2.02), and the geometric mean ratio of peak
      concentrations was 1.47 (90%CI 1.30 to 1.65); the 90%CIs were outside of the
      equivalence limits of 0.82 to 1.22, indicating an effect of vemurafenib on
      digoxin. Multiple oral doses of vemurafenib were generally well tolerated, with
      an adverse event profile similar to that previously seen in phase 2 and 3 studies
      of vemurafenib monotherapy. This study confirmed vemurafenib as an inhibitor of P
      gp in vivo with a statistically significant drug-drug interaction with digoxin.
      Caution should be exercised when dosing vemurafenib concurrently with P-gp
      substrates.

PMID- 29645281
TI  - The effects of infertility on perception of body in pregnancy: A comparative
      study.
AB  - PURPOSE: This study aimed to determine the effects of infertility on perception
      of body in pregnancy. DESIGN AND METHODS: This comparative study was conducted
      with 428 pregnant women (in vitro fertilization [IVF = 214, spontaneously
      conceived/SC = 214]). FINDINGS: The IVF group had a higher body image scale (BIS)
      score. Moreover, it was observed that the IVF group had more positive views on
      growth in the abdominal area, gaining weight, and changes in skin. The rates of
      taking precautions for these changes and thinking that these changes affected
      sexual life negatively were lower the in the IVF group. PRACTICE IMPLICATIONS:
      Infertility has a positive effect in perception of body in pregnancy.

PMID- 29645282
TI  - Quality control methods for linear accelerator radiation and mechanical axes
      alignment.
AB  - PURPOSE: The delivery accuracy of highly conformal dose distributions generated
      using intensity modulation and collimator, gantry, and couch degrees of freedom
      is directly affected by the quality of the alignment between the radiation beam
      and the mechanical axes of a linear accelerator. For this purpose, quality
      control (QC) guidelines recommend a tolerance of +/-1 mm for the coincidence of
      the radiation and mechanical isocenters. Traditional QC methods for assessment of
      radiation and mechanical axes alignment (based on pointer alignment) are time
      consuming and complex tasks that provide limited accuracy. In this work, an
      automated test suite based on an analytical model of the linear accelerator
      motions was developed to streamline the QC of radiation and mechanical axes
      alignment. METHODS: The proposed method used the automated analysis of
      megavoltage images of two simple task-specific phantoms acquired at different
      linear accelerator settings to determine the coincidence of the radiation and
      mechanical isocenters. The sensitivity and accuracy of the test suite were
      validated by introducing actual misalignments on a linear accelerator between the
      radiation axis and the mechanical axes using both beam steering and mechanical
      adjustments of the gantry and couch. RESULTS: The validation demonstrated that
      the new QC method can detect sub-millimeter misalignment between the radiation
      axis and the three mechanical axes of rotation. A displacement of the radiation
      source of 0.2 mm using beam steering parameters was easily detectable with the
      proposed collimator rotation axis test. Mechanical misalignments of the gantry
      and couch rotation axes of the same magnitude (0.2 mm) were also detectable using
      the new gantry and couch rotation axis tests. For the couch rotation axis, the
      phantom and test design allow detection of both translational and tilt
      misalignments with the radiation beam axis. For the collimator rotation axis, the
      test can isolate the misalignment between the beam radiation axis and the
      mechanical collimator rotation axis from the impact of field size asymmetry. The
      test suite can be performed in a reasonable time (30-35 min) due to simple
      phantom setup, prescription-based beam delivery, and automated image analysis. As
      well, it provides a clear description of the relationship between axes. After
      testing the sensitivity of the test suite to beam steering and mechanical errors,
      the results of the test suite were used to reduce the misalignment errors of the
      linac to less than 0.7-mm radius for all axes. CONCLUSIONS: The proposed test
      suite offers sub-millimeter assessment of the coincidence of the radiation and
      mechanical isocenters and the test automation reduces complexity with improved
      efficiency. The test suite results can be used to optimize the linear
      accelerator's radiation to mechanical isocenter alignment by beam steering and
      mechanical adjustment of gantry and couch.

PMID- 29645284
TI  - Fatal chlorine gas exposure at a metal recycling facility: Case report.
AB  - At least four workers at a metal recycling facility were hospitalized and one
      died after exposure to chlorine gas when it was accidentally released from an
      intact, closed-valved cylinder being processed for scrap metal. This
      unintentional chlorine gas release marks at least the third such incident at a
      metal recycling facility in the United States since 2010. We describe the fatal
      case of the worker whose clinical course was consistent with acute respiratory
      distress syndrome (ARDS) following exposure to high concentrations of chlorine
      gas. This case report emphasizes the potential risk of chlorine gas exposure to
      metal recycling workers by accepting and processing intact, closed-valved
      containers. The metal recycling industry should take steps to increase awareness
      of this established risk to prevent future chlorine gas releases. Additionally,
      public health practitioners and clinicians should be aware that metal recycling
      workers are at risk for chlorine gas exposure.

PMID- 29645283
TI  - Sympathoexcitation following intermittent hypoxia in rat is mediated by
      circulating angiotensin II acting at the carotid body and subfornical organ.
AB  - KEY POINTS: In anaesthetized rats, acute intermittent hypoxia increases
      sympathetic nerve activity, sympathetic peripheral chemoreflex sensitivity and
      central sympathetic-respiratory coupling. Renin-angiotensin system inhibition
      prevents the sympathetic effects of intermittent hypoxia, with intermittent
      injections of angiotensin II into the systemic circulation replicating these
      effects. Bilateral carotid body denervation reduces the sympathetic effects of
      acute intermittent hypoxia and eliminates the increases in chemoreflex
      sensitivity and sympathetic-respiratory coupling. Pharmacological inhibition of
      the subfornical organ also reduces the sympathetic effects of acute intermittent
      hypoxia, although it has no effect on the increases in chemoreflex sensitivity
      and central sympathetic-respiratory coupling. Combining both interventions
      eliminates the sympathetic effects of both intermittent hypoxia and angiotensin
      II. ABSTRACT: Circulating angiotensin II (Ang II) is vital for arterial pressure
      elevation following intermittent hypoxia in rats, although its importance in the
      induction of sympathetic changes is unclear. We tested the contribution of the
      renin-angiotensin system to the effects of acute intermittent hypoxia (AIH) in
      anaesthetized and ventilated rats. There was a 33.7 +/- 2.9% increase in
      sympathetic nerve activity (SNA), while sympathetic chemoreflex sensitivity and
      central sympathetic-respiratory coupling increased by one-fold following AIH. The
      sympathetic effects of AIH were prevented by blocking angiotensin type 1
      receptors with systemic losartan. Intermittent systemic injections of Ang II
      (Int.Ang II) elicited similar sympathetic responses to AIH. To identify the
      neural pathways responsible for the effects of AIH and Int.Ang II, we performed
      bilateral carotid body denervation, which reduced the increase in SNA by 56% and
      45%, respectively. Conversely, pharmacological inhibition of the subfornical
      organ (SFO), an established target of circulating Ang II, reduced the increase in
      SNA following AIH and Int.Ang II by 65% and 59%, respectively, although it did
      not prevent the sensitization of the sympathetic peripheral chemoreflex, nor the
      increase in central sympathetic-respiratory coupling. Combined carotid body
      denervation and inhibition of the SFO eliminated the enhancement of SNA following
      AIH and Int.Ang II. Repeated systemic injections of phenylephrine caused an
      elevation in SNA similar to AIH, and this effect was prevented by a renin
      inhibitor, aliskiren. Our findings show that the sympathetic effects of AIH are
      the result of RAS-mediated activations of the carotid bodies and the SFO.

PMID- 29645285
TI  - Cardiovascular Safety of the beta3 -Adrenoceptor Agonist Mirabegron and the
      Antimuscarinic Agent Solifenacin in the SYNERGY Trial.
AB  - There have been concerns that treatment of overactive bladder with beta3 
      adrenoceptor agonists may potentially have detrimental cardiovascular (CV) side
      effects. We evaluated the CV safety of mirabegron, a beta3 -adrenoceptor agonist,
      alone and in combination therapy with the antimuscarinic agent solifenacin. The
      SYNERGY trial was a multinational, multicenter, randomized, double-blind,
      parallel-group, placebo and active-controlled phase 3 trial. Patients were
      randomized to receive solifenacin 5 mg + mirabegron 50 mg (combination 5 + 50
      mg), solifenacin 5 mg + mirabegron 25 mg (combination 5 + 25 mg), solifenacin 5
      mg monotherapy, mirabegron 25 mg monotherapy, mirabegron 50 mg monotherapy, or
      placebo for a 12-week double-blind treatment period. A total of 3398 patients
      were included in the study. Mean changes from baseline to the end of therapy in
      ECG parameters were similar across treatment groups, although there was an
      increase in heart rate of 1 beat/minute in the mirabegron treatment groups. There
      were no clinically meaningful differences in change from baseline in QTcF between
      monotherapies and placebo and between monotherapies and combination therapy.
      There were very few major CV events: 1 of 853 (0.1%) with a nonfatal myocardial
      infarction in the combination 5 + 25 mg group, 2 of 848 (0.2%) with a nonfatal
      stroke in the combination 5 + 50 mg group, and no events in the other groups.
      This CV safety analysis of the combination of mirabegron and solifenacin showed
      rates of CV events comparable with those for monotherapy treatments based on
      assessments of vital signs, electrocardiograms, and adjudicated CV events.

PMID- 29645286
TI  - Effect of curing conditions on physical and chemical properties of MTA.
AB  - AIM: To evaluate setting time, pH, solubility and surface roughness of MTA+ and
      ProRoot MTA and characterize their hydration under several curing conditions.
      METHODOLOGY: Specimens were prepared to evaluate setting time (n = 6 for each
      group, specimen dimensions 10 * 8 * 5 mm), solubility (n = 6 for each group,
      specimen dimension 20 mm in diameter and 1.5 mm thick) after 1 and 28 days, pH (n
      = 10 for each group, specimen dimensions 10 mm in diameter and 1 mm thick) after
      1, 7, 14, 21 and 28 days and surface roughness (n = 10 for each group, specimen
      dimensions 4 mm in diameter and 3 mm high) after 28 days when cements were cured
      at 95% humidity or immersed in saline or HBSS at 37  degrees C. The powder and
      liquid were mechanically mixed by an amalgamator. The set materials were
      characterized using X-ray diffraction analysis, scanning electron microscopy and
      X-ray energy-dispersive analysis. Statistical comparisons were employed using one
      way anova. The level of significance was set at P = 0.05. RESULTS: Setting time
      was significantly shorter when cements were cured at 95% humidity compared to
      those in saline (P < 0.001) and HBSS (P < 0.001). Setting time of MTA+ was
      significantly shorter than that of ProRoot MTA (P < 0.001), which had a
      significantly higher pH than MTA+ (P < 0.05) for all periods and immersion
      liquids. After immersion in saline, MTA+ was significantly less soluble than
      ProRoot MTA (P < 0.001); when immersed in HBSS, no significant difference was
      found (P = 1.00). The surface roughness of both cements was affected when exposed
      to HBSS (P < 0.001 for both cements) and saline (P < 0.001 for both cements).
      Storage in HBSS created a homogenous surface; incubation in saline or humidity
      created a biphasic surface. The main crystalline phases in both cements were
      tricalcium silicate, bismuth oxide and calcium hydroxide. CONCLUSIONS: MTA+ had a
      shorter setting time than ProRoot MTA, promoted lower pH and had lower solubility
      in saline. Curing conditions affected the surface roughness and microstructure of
      the cements.

PMID- 29645289
TI  - Gingival leukemic infiltration as the first manifestation of acute myeloid
      leukemia.
AB  - Leukemic infiltration of the gingival tissue associated or not with gingival
      enlargement may be the first manifestation of acute leukemia, despite being
      rarely reported in the literature. A 10-year-old female patient presented with a
      1-month history of an asymptomatic, firm, and pinkish-red generalized gingival
      overgrowth. There was no bone resorption. Incisional biopsy of the gingival
      tissue was performed, with histopathological examination revealing a diffuse and
      hypercellular infiltration of monocytoid cells. The patient was referred to a
      hematologist and underwent a bone marrow biopsy, which led to a conclusive
      diagnosis of acute myeloid leukemia. The patient was treated with chemotherapy
      and we observed regression of gingival enlargement after 4 weeks from the initial
      therapy.

PMID- 29645290
TI  - Mesoporous MFI Zeolite with a 2D Square Structure Directed by Surfactants with an
      Azobenzene Tail Group.
AB  - Mesoporous MFI zeolites (MMZs) have been constructed by using the surfactant
      containing azobenzene segment in the hydrophobic tail. The cylindrical pi-pi
      stacking of azeobenzene groups is considered to be the key factor to form the
      ordered mesostructure through cooperative structural matching and the
      rearrangement of MFI frameworks. The mesostructure has been tuned from a
      disordered hierarchical arrangement into an ordered 2D square p4mm structure by
      changing the length of the alkyl chain between the diquaternary ammonium head
      group and azobenzene group. The geometric matching between the MFI zeolitic
      framework and the alkyl chain length plays an important role in the construction
      of the crystallographically correlated mesostructure with 2D square ordering. A
      combination of X-ray diffraction patterns and electron microscopy studies
      provides visible evidence for the mesostructural transformation from a short
      range hexagonal or lamellar ordering to 2D square mesostructure.

PMID- 29645291
TI  - A simple, low-cost and robust capillary zone electrophoresis method with
      capacitively coupled contactless conductivity detection for the routine
      determination of four selected penicillins in money-constrained laboratories.
AB  - A simple and robust capillary zone electrophoresis method was developed and
      validated for the determination of amoxicillin and clavulanate, ampicillin,
      phenoxymethyl penicillin (Pen V) as well as flucloxacillin. Capacitively coupled
      contactless conductivity detection was employed as detection mode that makes CE a
      simple and economic tool for money-constrained laboratories. The developed method
      is straightforward and user-friendly. It offers good sensitivity and sufficient
      selectivity for the routine assay of the selected penicillins. The
      repeatabilities were <1.9% RSD for relative peak areas and <1% RSD for migration
      times for all the analytes. The method showed good linearity (R2  > 0.995) within
      the 80-120% range of the target concentration (0.5 mg/mL) for each antibiotic.
      The accuracy of the method, evaluated by standard fortification at three levels,
      was good for all the analytes. An extended robustness study was performed by
      varying +/-10% of the optimum value of TRIS concentration, l-histidine
      concentration and temperature in a full factorial design at two levels. This was
      to evaluate larger than usual variability of factors on the assay value, in order
      to better cover potential global variance in lab conditions and equipment.
      Finally, the method was applied for the determination of percent (%) content of
      all antibiotics in available formulations.

PMID- 29645293
TI  - Thiazole orange as an everyday replacement for ethidium bromide and costly DNA
      dyes for electrophoresis.
AB  - DNA gel electrophoresis is a standard tool of biochemistry and molecular biology
      laboratories. The common dye ethidium bromide suffers from toxicity concerns and
      requires the use of damaging ultraviolet light. We observe that exposing plasmid
      DNA to a UV transilluminator for only 1 s results in detectable loss of colonies
      following transformation, suggesting rapid accumulation of DNA damage. SYBR Safe,
      a commercial product, is marketed as a safe alternative to ethidium bromide and
      has excellent sensitivity with nondamaging blue light, but suffers from
      prohibitively high costs. We show that thiazole orange, the parent compound of
      SYBR Safe, is an excellent, simple, and inexpensive alternative to these dyes. It
      is excitable with safe blue light or UV light, with DNA detection limits in
      agarose gels similar to ethidium bromide and SYBR Safe (1-2 ng/lane). Thiazole
      orange safely allows the use of nondamaging blue light at the same cost as
      ethidium bromide.

PMID- 29645294
TI  - Of Thiols and Disulfides: Methods for Chemoselective Formation of Asymmetric
      Disulfides in Synthetic Peptides and Polymers.
AB  - In protein or peptide chemistry, thiols are frequently chosen as a chemical
      entity for chemoselective modification reactions. Although it is a well
      established methodology to address cysteines and homocysteines in aqueous media
      to form S-C bonds, possibilities for the chemoselective formation of asymmetric
      disulfides have been less approached. Focusing on bioreversibility in conjugation
      chemistry, the formation of disulfide bonds is highly desirable for the
      attachment of thiol-containing bioactive agents to proteins or in cross-linking
      reactions, because disulfide bonds can combine stability in blood with
      degradability inside cells. In this Concept article, recent approaches in the
      field of activating groups for thiol moieties incorporated in peptide and polymer
      materials are highlighted. Advantageous combinations of stability during
      synthesis of the material with high reactivity towards thiols are explored
      focusing on simplification and prevention of side reactions as well as additional
      deprotection and activation steps prior to disulfide formation. Moreover,
      applications of this chemistry are highlighted and future perspectives are
      envisioned.

PMID- 29645297
TI  - Computer simulation of the enantioselective separation of weak bases in an online
      capillary electrophoresis based microanalysis configuration comprising sulfated
      cyclodextrin as selector.
AB  - Computer simulation was utilized to characterize the electrophoretic processes
      occurring after reactant mixing in an online assay format used for monitoring the
      enantioselective N-demethylation of ketamine to norketamine in the presence of
      highly sulfated gamma-cyclodextrin (HS-gamma-CD). The incubated reaction mixture
      (at pH 7.4 and without chiral selector) is bracketed by a low pH BGE containing
      2% HS-gamma-CD as chiral selector, thereby forming a discontinuous buffer system.
      Upon power application, simulation provides insight into the formation of moving
      boundaries and new zones together with the prediction of the behavior of ketamine
      and norketamine enantiomers. The analytes first migrate cationically in a zone
      electrophoretic manner until they come in contact with HS-gamma-CD upon which
      enantioseparation is initiated. Complexation has a focusing effect and the
      electrophoretic transport becomes reversed, that is, toward the anode. Simulation
      revealed that the initial conditions for the chiral separation, including buffer
      components concentrations, pH, and ionic strength, are different than those in
      the BGE. As a consequence thereof, the experimentally determined complexation
      parameters for the BGE were unable to correctly describe the migration behavior
      of the analytes in this column section. An increase in the input binding
      constants by a factor of two to four, as a result of the decreased ionic
      strength, resulted in simulation data that agreed with experimental findings.

PMID- 29645296
TI  - Effects of JAK1/2 inhibition on bone marrow stromal cells of myeloproliferative
      neoplasm (MPN) patients and healthy individuals.
AB  - OBJECTIVE: Philadelphia-negative myeloproliferative neoplasms (MPNs) commonly
      share hyperactive JAK-STAT signaling affecting hematopoietic stem cells (HSC) and
      their progeny. The JAK1/2 inhibitor Ruxolitinib has remarkable clinical efficacy,
      including spleen reduction, improvement of constitutional symptoms, and bone
      marrow (BM) fibrosis reversal. Whether this is due to inhibition of JAK2-mutated
      HSC only, or whether Ruxolitinib also affects BM stroma is not known. METHODS:
      This study investigated potential effects of Ruxolitinib on BM mesenchymal
      stromal cells (MSC), which are not only major regulators of hematopoiesis but
      also contribute to fibrosis, from 10 healthy donors and 7 JAK2V617F -positive MPN
      patients. RESULTS: Ruxolitinib moderately inhibited the growth of healthy donor
      MSC (HD-MSC) and MSC from JAK2V617F+ MPN patients (P-MSC) in short- and long-term
      assays. The clonogenic potential of HD-MSC was not affected by Ruxolitinib. JAK
      STAT signaling, however, was markedly inhibited in both HD-MSC and P-MSC, the
      latter of which showed higher expression of fibrosis-associated and hematopoiesis
      maintenance genes. Moreover, Ruxolitinib reduced MSC secretion of MCP-1 and IL-6.
      CONCLUSION: Ruxolitinib affected JAK2 signaling in MSC at clinically relevant
      doses, which is likely to contribute to the normalization of the inflammatory
      milieu in MPNs. Thus, combined HSC and stroma-directed interventions have the
      potential to improve constitutional symptoms and reduce stromal proliferation in
      MPNs.

PMID- 29645298
TI  - In Situ Fabrication of Hierarchical MTW Zeolite via Nanoparticle Assembly by a
      Tailored Simple Organic Molecule.
AB  - Amphiphilic surfactants are widely used as templates to synthesize hierarchically
      structured zeolites due to their multiple functions; however, piloting such new
      dual-functional templates is limited by their time-consuming nature and high
      cost. Herein, a simple organic molecule, without a long hydrophobic alkyl chain,
      was tailored from a gemini-type, poly-quaternary ammonium surfactant, and
      effectively used as a dual-porogenic template to synthesize hierarchical MTW
      zeolite. Upon a range of synthesis parameter optimizations, our detailed
      characterization suggested that the hierarchical MTW zeolite would completely
      crystallize within 36 hours from the surface to the inside of quasi-spherical
      particles through in situ consumption of amorphous silicon and aluminum species;
      much faster than most of the hierarchical MTW zeolites generated by conventional
      methods. Moreover, the as-prepared hierarchical MTW zeolite exhibited 4 times
      higher catalytic performance and lifetime of benzene-propene alkylation compared
      to conventional MTW zeolite, while the introduced crystalline mesopores are of
      benefit to diffuse reactants, products, and coke depositions. Our strategy
      broadens the design of new templates in more effective ways to facilely
      synthesize versatile hierarchical zeolites for diverse applications, especially
      for those in which macromolecules are involved.

PMID- 29645299
TI  - Orthogonal Clickable Iron Oxide Nanoparticle Platform for Targeting, Imaging, and
      On-Demand Release.
AB  - A versatile iron oxide nanoparticle platform is reported that can be orthogonally
      functionalized to obtain highly derivatized nanomaterials required for a wide
      variety of applications, such as drug delivery, targeted therapy, or imaging.
      Facile functionalization of the nanoparticles with two ligands containing
      isocyanate moieties allows for high coverage of the surface with maleimide and
      alkyne groups. As a proof-of-principle, the nanoparticles were subsequently
      functionalized with a fluorophore as a drug model and with biotin as a targeting
      ligand towards tumor cells through Diels-Alder and azide-alkyne cycloaddition
      reactions, respectively. The thermoreversibility of the Diels-Alder product was
      exploited to induce the on-demand release of the loaded molecules by magnetic
      hyperthermia. Additionally, the nanoparticles were shown to target cancer cells
      through in vitro experiments, as analyzed by magnetic resonance imaging.

PMID- 29645300
TI  - A comparison of extraction systems for plant water stable isotope analysis.
AB  - RATIONALE: The stable isotope ratios of water (delta2 H and delta18 O values)
      have been widely used to trace water in plants in a variety of physiological,
      ecohydrological, biogeochemical and hydrological studies. In such work, the
      analyte must first be extracted from samples, prior to isotopic analysis. While
      cryogenic vacuum distillation is currently the most widely used method reported
      in the literature, a variety of extraction-collection-analysis methods exist. A
      formal inter-method comparison on plant tissues has yet to be carried out.
      METHODS: We performed an inter-method comparison of six plant water extraction
      techniques: direct vapour equilibration, microwave extraction, two unique
      versions of cryogenic vacuum distillation, centrifugation, and high-pressure
      mechanical squeezing. These methods were applied to four isotopically unique
      plant portions (head, stem, leaf, and root crown) of spring wheat (Triticum
      aestivum L.). Extracted plant water was analyzed via spectrometric (OA-ICOS) and
      mass-based (IRMS) analysis systems when possible. Spring wheat was grown under
      controlled conditions with irrigation inputs of a known isotopic composition.
      RESULTS: The tested methods of extraction yielded markedly different isotopic
      signatures. Centrifugation, microwave extraction, direct vapour equilibration,
      and high-pressure mechanical squeezing produced water more enriched in 2 H and 18
      O content. Both cryogenic vacuum distillation systems and the high-pressure
      mechanical squeezing method produced water more depleted in 2 H and 18 O content,
      depending upon the plant portion extracted. The various methods also produced
      differing concentrations of co-extracted organic compounds, depending on the mode
      of extraction. Overall, the direct vapor equilibration method outperformed all
      other methods. CONCLUSIONS: Despite its popularity, cryogenic vacuum distillation
      was outperformed by the direct vapor equilibration method in terms of limited co
      extraction of volatile organic compounds, rapid sample throughput, and near
      instantaneous returned stable isotope results. More research is now needed with
      other plant species, especially woody plants, to see how far the findings from
      this study could be extended.

PMID- 29645301
TI  - Collision-induced dissociation of [UVI O2 (ClO4 )]+ revisited: Production of [UVI
      O2 (Cl)]+ and subsequent hydrolysis to create [UVI O2 (OH)].
AB  - RATIONALE: In a previous study [Rapid Commun Mass Spectrom. 2004;18:3028-3034],
      collision-induced dissociation (CID) of [UVI O2 (ClO4 )]+ appeared to be
      influenced by the high levels of background H2 O in a quadrupole ion trap. The
      CID of the same species was re-examined here with the goal of determining whether
      additional, previously obscured dissociation pathways would be revealed under
      conditions in which the level of background H2 O was lower. METHODS: Water- and
      methanol-coordinated [UVI O2 (ClO4 )]+ precursor ions were generated by
      electrospray ionization. Multiple-stage tandem mass spectrometry (MSn ) for CID
      and ion-molecule reaction (IMR) studies was performed using a linear ion trap
      mass spectrometer. RESULTS: Under conditions of low background H2 O, CID of [UVI
      O2 (ClO4 )]+ generates [UVI O2 (Cl)]+ , presumably by elimination of two O2
      molecules. Using low isolation/reaction times, we found that [UVI O2 (Cl)]+ will
      undergo an IMR with H2 O to generate [UVI O2 (OH)]+ . CONCLUSIONS: With lower
      levels of background H2 O, CID experiments reveal that the intrinsic dissociation
      pathway for [UVI O2 (ClO4 )]+ leads to [UVI O2 (Cl)]+ , apparently by loss of two
      O2 molecules. We propose that the results reported in the earlier CID study
      reflected a two-step process: initial formation of [UVI O2 (Cl)]+ by CID,
      followed by a very rapid hydrolysis reaction to leave [UVI O2 (OH)]+ .

PMID- 29645302
TI  - Carboxylates as Nucleophiles in the Enantioselective Ring-Opening of
      Formylcyclopropanes under Iminium Ion Catalysis.
AB  - In this work, carboxylic acids, which are typically regarded as poor
      nucleophiles, are demonstrated to be competent reagents to promote the ring
      opening of formylcyclopropanes after activation of the latter through iminium ion
      formation. Under optimized reaction conditions, a variety of gamma-acyloxy
      substituted aldehydes can be obtained in high yields and enantioselectivities
      through the desymmetrization of substituted meso-formylcyclopropanes in the
      presence of a chiral secondary amine as catalyst.

PMID- 29645303
TI  - Unimolecular reactivity of organotrifluoroborate anions, RBF3- , and their alkali
      metal cluster ions, M(RBF3 )2- (M = Na, K; R = CH3 , CH3 CH2 , CH3 (CH2 )3 , CH3
      (CH2 )5 , c-C3 H5 , C6 H5 , C6 H5 CH2 , CH2 CHCH2 , CH2 CH, C6 H5 CO).
AB  - RATIONALE: Potassium organotrifluoroborates (RBF3 K) are important reagents used
      in organic synthesis. Although mass spectrometry is commonly used to confirm
      their molecular formulae, the gas-phase fragmentation reactions of
      organotrifluoroborates and their alkali metal cluster ions have not been
      previously reported. METHODS: Negative-ion mode electrospray ionization (ESI)
      together with collision-induced dissociation (CID) using a triple quadrupole mass
      spectrometer were used to examine the fragmentation pathways for RBF3- (where R =
      CH3 , CH3 CH2 , CH3 (CH2 )3 , CH3 (CH2 )5 , c-C3 H5 , C6 H5 , C6 H5 CH2 , CH2
      CHCH2 , CH2 CH, C6 H5 CO) and M(RBF3 )2- (M = Na, K), while density functional
      theory (DFT) calculations at the M06/def2-TZVP level were used to examine the
      structures and energies associated with fragmentation reactions for R = Me and
      Ph. RESULTS: Upon CID, preferentially elimination of HF occurs for RBF3- ions for
      systems where R = an alkyl anion, whereas R- formation is favoured when R = a
      stabilized anion. At higher collision energies loss of F- and additional HF
      losses are sometimes observed. Upon CID of M(RBF3 )2- , formation of RBF3- is the
      preferred pathway with some fluoride transfer observed only when M = Na. The DFT
      calculated relative thermochemistry for competing fragmentation pathways is
      consistent with the experiments. CONCLUSIONS: The main fragmentation pathways of
      RBF3- are HF elimination and/or R- loss. This contrasts with the fragmentation
      reactions of other organometallate anions, where reductive elimination, beta
      hydride transfer and bond homolysis are often observed. The presence of fluoride
      transfer upon CID of Na(RBF3 )2- but not K(RBF3 )2- is in agreement with the
      known fluoride affinities of Na+ and K+ and can be rationalized by Pearson's HSAB
      theory.

PMID- 29645304
TI  - C(sp3 )-H Cyanation Promoted by Visible-Light Photoredox/Phosphate Hybrid
      Catalysis.
AB  - Inspired by the reaction mechanism of photo-induced DNA cleavage in nature, a
      C(sp3 )-H cyanation reaction promoted by visible-light photoredox/phosphate
      hybrid catalysis was developed. Phosphate radicals, generated by one-electron
      photooxidation of phosphate salt, functioned as a hydrogen-atom-transfer catalyst
      to produce nucleophilic carbon radicals from C(sp3 )-H bonds with a high bond
      dissociation energy. The resulting carbon radicals were trapped by a cyano
      radical source (TsCN) to produce the C-H cyanation products. Due to the high
      functional-group tolerance and versatility of the cyano group, the reaction will
      be useful for realizing streamlined building block syntheses and late-stage
      functionalization of drug-like molecules.

PMID- 29645305
TI  - Evolution of a xenobiotic degradation pathway: formation and capture of the
      labile phthaloyl-CoA intermediate during anaerobic phthalate degradation.
AB  - Xenobiotic phthalates are industrially produced on the annual million ton scale.
      The oxygen-independent enzymatic reactions involved in anaerobic phthalate
      degradation have only recently been elucidated. In vitro assays suggested that
      phthalate is first activated to phthaloyl-CoA followed by decarboxylation to
      benzoyl-CoA. Here, we report the heterologous production and characterization of
      the enzyme initiating anaerobic phthalate degradation from 'Aromatoleum
      aromaticum': a highly specific succinyl-CoA:phthalate CoA transferase (SPT, class
      III CoA transferase). Phthaloyl-CoA formed by SPT accumulated only to sub
      micromolar concentrations due to the extreme lability of the product towards
      intramolecular substitution with a half-life of around 7 min. Upon addition of
      excess phthaloyl-CoA decarboxylase (PCD), the combined activity of both enzymes
      was drastically shifted towards physiologically relevant benzoyl-CoA formation.
      In conclusion, a massive overproduction of PCD in phthalate-grown cells to
      concentrations >140 MUM was observed that allowed for efficient phthaloyl-CoA
      conversion at concentrations 250-fold below the apparent Km -value of PCD. The
      results obtained provide insights into an only recently evolved xenobiotic
      degradation pathway where a massive cellular overproduction of PCD compensates
      for the formation of the probably most unstable CoA ester intermediate in
      biology.

PMID- 29645306
TI  - Angled Vortex Fluidic Mediated Multicomponent Photocatalytic and Transition Metal
      Catalyzed Reactions.
AB  - The dynamic thin film formed in an angled rapidly rotating tube in a vortex
      fluidic device (VFD) is effective in facilitating multicomponent reactions (MCRs)
      as photocatalytic or metal-mediated processes. Here, we demonstrate the utility
      of the VFD by using two known MCRs, an Ugi-type three component reaction and an
      A3 -coupling reaction. The Ugi-type reaction can be done in either confined or
      continuous-flow modes of operation of the microfluidic platform whereas the A3 
      coupling reaction was optimized for the confined mode of operation. The examples
      tested gave excellent yields with short reaction times.

PMID- 29645308
TI  - Yet another database?

PMID- 29645307
TI  - Circular dichroism studies of low molecular weight hydrogelators: The use of SRCD
      and addressing practical issues.
AB  - Circular dichroism (CD) spectroscopy has been used extensively for the
      investigation of the conformation and configuration of chiral molecules, but its
      use for evaluating the mode of self-assembly in soft materials has been limited.
      Herein, we report a protocol for the study of such materials by electronic CD
      spectroscopy using commercial/benchtop instruments and synchrotron radiation (SR)
      using the B23 beamline available at Diamond Light Source. The use of the B23
      beamtime for SRCD was advantageous because of the unique enhanced spatial
      resolution achieved because of its highly collimated and small beamlight cross
      section (ca. 250 MUm) and higher photon flux in the far UV region (175-250 nm)
      enhancing the signal-to-noise ratio relative to benchtop CD instruments. A set of
      low molecular weight (LMW) hydrogelators, comprising two Fmoc-protected
      enantiomeric monosaccharides and one Fmoc dipeptide (Fmoc-FF), were studied. The
      research focused on the optimization of sample preparation and handling, which
      then enabled the characterization of sample conformational homogeneity and
      thermal stability. CD spectroscopy, in combination with other spectroscopic
      techniques and microscopy, will allow a better insight into the self-assembly of
      chiral building blocks into higher order structural architectures.

PMID- 29645309
TI  - Hydrazo-CEST: Hydrazone-Dependent Chemical Exchange Saturation Transfer Magnetic
      Resonance Imaging Contrast Agents.
AB  - The rapid formation of hydrazones under physiological conditions was exploited
      for the detection of aldehydes through chemical exchange saturation transfer
      magnetic resonance imaging (CEST-MRI). A metal-free, diamagnetic contrast agent
      derived from N-amino anthranilic acid was introduced, which selectively "turned
      on" upon hydrazone formation through an effect termed Hydrazo-CEST. While the
      hydrazine form of the probe produced no CEST-MRI signal enhancement, the
      formation of the aryl hydrazone resulted in >20 % intensity decrease in the bulk
      water signal through the CEST effect, as measured by 300 MHz 1 H NMR, 3 T and 7 T
      MRI. Both the electronic contributions of the N-amino anthranilate and the
      aldehyde binding partner were shown to directly impact the exchange rate of the
      proton on the ring-proximal nitrogen, and thus the imaging signal. Additionally,
      the presence of the carboxylic acid moiety ortho to the hydrazine was necessary
      not only for contrast production, but also for rapid hydrazone formation and
      prolonged hydrazone product stability under physiological conditions. This work
      provided the first example of an MRI-based contrast agent capable of a "turn on"
      response upon reaction with bioactive aldehydes, and outlined both the structural
      and electronic requirements to expand on Hydrazo-CEST, a novel, hydrazone
      dependent subtype of diamagnetic CEST-MRI.

PMID- 29645311
TI  - Copyright Page.

PMID- 29645310
TI  - Half Title.

PMID- 29645312
TI  - FIGO Board.

PMID- 29645313
TI  - Supplement Title Page.

PMID- 29645315
TI  - Cell and molecular mechanisms behind diet-induced hypothalamic inflammation and
      obesity.
AB  - Diet-induced obesity (DIO) is associated with chronic, low-grade inflammation in
      the hypothalamus, a key regulator of energy homeostasis. Current studies have
      revealed the involvement of different cell types, as well as cell and molecular
      mechanisms, that contribute to diet-induced hypothalamic inflammation (DIHI) and
      DIO. Subsequent to the discovery that high-fat diet and saturated fatty acids
      increase the expression of hypothalamic cytokines prior to weight gain, research
      has focused on understanding the cellular and molecular mechanisms underlying
      these changes, in addition to the role of inflammation in the pathogenesis of
      obesity. Recent studies have proposed that the inhibition of pro-inflammatory
      pathways in microglia and astrocytes is sufficient to protect against DIHI and
      prevent obesity. In addition, impairment of intracellular and epigenetic
      mechanisms, such as hypothalamic autophagy and changes in the methylation pattern
      of certain genes, have been implicated in susceptibility to DIHI and DIO.
      Interestingly, a sexual dimorphism has been found during DIO in hypothalamic
      inflammation, glial activation and metabolic diseases, and recent data support an
      important role of sex steroids in DIHI. These new exciting findings uncover novel
      obesity pathogenic mechanisms and provide targets to develop therapeutic
      approaches.

PMID- 29645317
TI  - Slow Infusion of Low-dose Ketamine Reduces Bothersome Side Effects Compared to
      Intravenous Push: A Double-blind, Double-dummy, Randomized Controlled Trial.
AB  - OBJECTIVE: We compared the analgesic efficacy and incidence of side effects when
      low-dose (0.3 mg/kg) ketamine (LDK) is administered as a slow infusion (SI) over
      15 minutes versus an intravenous push (IVP) over 1 minute. METHODS: This was a
      prospective, randomized, double-blind, double-dummy, placebo-controlled trial of
      adult ED patients presenting with moderate to severe pain (numerical rating scale
      [NRS] score >= 5). Patients received 0.3 mg/kg ketamine administered either as a
      SI or a IVP. Our primary outcome was the proportion of patients experiencing any
      psychoperceptual side effect over 60 minutes. A secondary outcome was incidence
      of moderate or greater psychoperceptual side effects. Additional outcomes
      included reduction in pain NRS scores at 60 minutes and percent maximum summed
      pain intensity difference (%SPID). RESULTS: Fifty-nine participants completed the
      study. A total of 86.2% of the IVP arm and 70.0% of the SI arm experienced any
      side effect (difference = 16.2%, 95% confidence interval [CI] = -5.4 to 37.8). We
      found a large reduction in moderate or greater psychoperceptual side effects with
      SI administration-75.9% reported moderate or greater side effects versus 43.4% in
      the SI arm (difference = 32.5%, 95% CI = 7.9 to 57.1). Additionally, the IVP arm
      experienced more hallucinations (n = 8, 27.6%) than the SI arm (SI n = 2, 6.7%,
      difference = 20.9%, 95% CI = 1.8 to 43.4). We found no significant differences in
      analgesic efficacy. At 60 minutes, the mean %SPID values in the IVP and SI arms
      were 39.9 and 33.5%, respectively, with a difference of 6.5% (95% CI = -5.8 to
      18.7). CONCLUSION: Most patients who are administered LDK experience a
      psychoperceptual side effect regardless of administration via SI or IVP. However,
      patients receiving LDK as a SI reported significantly fewer moderate or greater
      psychoperceptual side effects and hallucinations with equivalent analgesia.

PMID- 29645319
TI  - It Saved My Life.

PMID- 29645316
TI  - Neuropeptide and steroid hormone mediators of neuroendocrine regulation.
AB  - To maintain the health and well-being of all mammals, numerous aspects of
      physiology are controlled by neuroendocrine mechanisms. These mechanisms
      ultimately enable communication between neurones and glands throughout the body
      and are centrally mediated by neuropeptides and/or steroid hormones. A recent
      session at the International Workshop in Neuroendocrinology highlighted the
      essential roles of some of these neuropeptide and steroid hormone mediators in
      the neuroendocrine regulation of stress-, reproduction- and behaviour-related
      processes. Accordingly, the present review highlights topics presented in this
      session, including the role of the neuropeptides corticotrophin-releasing factor
      and gonadotrophin-releasing hormone in stress and reproductive physiology,
      respectively. Additionally, it details an important role for gonadal sex steroids
      in the development of behavioural sex preference.

PMID- 29645318
TI  - Investigating the dynamics and polyanion binding sites of fibroblast growth
      factor-1 using hydrogen-deuterium exchange mass spectrometry.
AB  - In this study, we examined the local dynamics of acidic fibroblast growth factor
      (FGF-1) as well as the binding sites of various polyanions including poly
      sulfates (heparin and low MW heparin) and poly-phosphates (phytic acid and ATP)
      using hydrogen-deuterium exchange mass spectrometry (HX-MS). For local dynamics,
      results are analyzed at the peptide level as well as in terms of buried amides
      employing crystallographic B-factors and compared with a residue level heat map
      generated from HX-MS results. Results show that strand 4 and 5 and the turn
      between them to be the most flexible regions as was previously seen by NMR. On
      the other hand, the C-terminal strands 8, 9, and 10 appear to be more rigid which
      is also consistent with crystallographic B-factors as well as local dynamics
      studies conducted by NMR. Crystal structures of FGF-1 in complex with heparin
      have shown that heparin binds to N-terminal Asn18 and to C-terminal Lys105,
      Tryp107, Lys112, Lys113, Arg119, Pro121, Arg122, Gln127, and Lys128 indicating
      electrostatic forces as dominant interactions. Heparin binding as determined by
      HX-MS is consistent with crystallography data. Previous studies have also shown
      that other polyanions including low MW heparin, phytic acid and ATP dramatically
      increase the thermal stability of FGF-1. Using HX-MS, we find other poly anions
      tested bind in a similar manner to heparin, primarily targeting the turns in the
      lysine rich C-terminal region of FGF-1 along with two distinct N-terminal regions
      that contains lysines and arginines/histidines. This confirms the interactions
      between FGF-1 and polyanions are primary directed by electrostatics.

PMID- 29645320
TI  - A Dynamic Chemical Network for Cystinuria Diagnosis.
AB  - The study of molecular networks represents a conceptual revolution in chemistry.
      Building on previous knowledge and after understanding the rules of non-covalent
      interactions, the design of stimulus-responsive chemical systems is possible.
      Herein we report a new strategy, based on the reorganization of a dynamic
      chemical network that generates new fluorescent associations in the presence of
      cysteine or cystine. The binding and sensing units are encoded in the components
      that dynamically assemble and disassemble responding to external stimuli as a
      successful tool to detect both cysteine and cystine in aqueous media. Moreover,
      the dynamic sensing system works in human urine, as a prospective application for
      cystinuria diagnosis.

PMID- 29645321
TI  - Maternal perceptions of BRCA genetic counseling communication processes about
      disclosing cancer risk information to children and adult relatives.
AB  - OBJECTIVES: Using a novel measure, examine maternal perceptions of the process by
      which issues pertaining to family communication of BRCA test results are
      addressed during cancer genetic counseling. METHODS: After receiving BRCA
      results, mothers (N = 211) of minor-age children reported on their counseling
      experiences with providers using a communication process measure as well as other
      psychosocial variables. RESULTS: The novel Genetic Counseling Communication
      Process measure demonstrated good internal consistency of its 2 factors: patient
      led communication (Cronbach's alpha = 0.73) and provider-led communication
      (Cronbach's alpha = 0.82). Participants most often reported that discussions
      about family communication of BRCA test results to children and adult relatives
      were led only by their providers (38.2%-39.2%), as opposed to being led by the
      patient, both parties, or neither party. Providers were most likely to lead these
      discussions when mothers had stronger family histories of cancer and expressed
      more confidence about making a decision to talk to their children about BRCA.
      However, mothers typically led such discussions if they were raising older
      children and held more positive attitudes about pediatric BRCA testing.
      CONCLUSIONS: When the assessment of BRCA genetic counseling outcomes includes
      family communication to potentially at-risk relatives, we learned that most but
      not all sessions addressed this topic. Cancer family history, child age, and
      maternal attitudes are important co-factors in these patient-provider
      communication exchanges. Providers delivering BRCA genetic counseling should be
      attentive to mothers' information and support needs regarding communicating
      cancer genetic test results to at-risk relatives, including children.

PMID- 29645322
TI  - Cyclic and Lasso Peptides: Sequence Determination, Topology Analysis, and
      Rotaxane Formation.
AB  - A broadly applicable chemical cleavage methodology to facilitate MS/MS sequencing
      was developed for macrocyclic and lasso peptides, which hold promise as exciting
      new therapeutics. Existing methods such as Edman degradation, CNBr cleavage, and
      enzymatic digestion are either limited in scope or completely fail in cleavage of
      constrained nonribosomal peptides. Importantly, the new method was utilized for
      synthesizing a unique peptide-based rotaxane (both cyclic and threaded) from the
      lasso peptide, benenodin-1 DeltaC5.

PMID- 29645323
TI  - Dangerous relationships: biases in freshwater bioassessment based on observed to
      expected ratios.
AB  - The ecological assessment of freshwaters is currently primarily based on
      biological communities and the reference condition approach (RCA). In the RCA,
      the communities in streams and lakes disturbed by humans are compared with
      communities in reference conditions with no or minimal anthropogenic influence.
      The currently favored rationale is using selected community metrics for which the
      expected values (E) for each site are typically estimated from environmental
      variables using a predictive model based on the reference data. The proportional
      differences between the observed values (O) and E are then derived, and the
      decision rules for status assessment are based on fixed (typically 10th or 25th)
      percentiles of the O/E ratios among reference sites. Based on mathematical
      formulations, illustrations by simulated data and real case studies representing
      such an assessment approach, we demonstrate that the use of a common quantile of
      O/E ratios will, under certain conditions, cause severe bias in decision making
      even if the predictive model would be unbiased. This is because the variance of
      O/E under these conditions, which seem to be quite common among the published
      applications, varies systematically with E. We propose a correction method for
      the bias and compare the novel approach to the conventional one in our case
      studies, with data from both reference and impacted sites. The results highlight
      a conceptual issue of employing ratios in the status assessment. In some cases
      using the absolute deviations instead provides a simple solution for the bias
      identified and might also be more ecologically relevant and defensible.

PMID- 29645324
TI  - Reactions of Fluoroalkenes with an Aluminium(I) Complex.
AB  - A series of industrially relevant fluoroalkenes react with a monomeric AlI
      complex. These reactions break strong sp2 and sp3 C-F bonds, and result in the
      formation of a diverse array of organoaluminium compounds. Mechanistic studies
      show that two mechanisms are likely in operation: 1) direct oxidative addition of
      the C-F bond to AlI occurs with retention of alkene stereochemistry, and 2)
      stepwise formation and decomposition of a metallocyclopropane intermediate occurs
      with inversion of alkene stereochemistry. As part of this mechanistic analysis,
      we have isolated the first aluminium metallocyclopropane complex from oxidative
      addition of an alkene to AlI . Remarkably this reaction is reversible and
      reductive elimination of the alkene occurs at higher temperature reforming AlI .
      Furthermore, in selected cases the organoaluminium products are susceptible
      toward beta-fluoride elimination to yield a double C-F activation pathway.

PMID- 29645325
TI  - Crowdsourcing as an Analytical Method: Metrology of Smartphone Measurements in
      Heritage Science.
AB  - This research assesses the precision, repeatability, and accuracy of crowdsourced
      scientific measurements, and whether their quality is sufficient to provide
      usable results. Measurements of colour and area were chosen because of the
      possibility of producing them with smartphone cameras. The quality of the
      measurements was estimated experimentally by comparing data contributed by
      anonymous participants in heritage sites with reference measurements of known
      accuracy and precision. Participants performed the measurements by taking
      photographs with their smartphones, from which colour and dimensional data could
      be extracted. The results indicate that smartphone measurements provided by
      citizen scientists can be used to measure changes in colour, but that the
      performance is strongly dependent on the measured colour coordinate. The same
      method can be used to measure areas when the difference in colour with the
      neighbouring areas is large enough. These results render the method useful in
      some heritage science contexts, but higher precision would be desirable.

PMID- 29645326
TI  - Palladium-Catalyzed para-Selective Alkylation of Electron-Deficient Arenes.
AB  - Intermolecular alkylations of electron-deficient arenes proceed with good para
      selectivity. Palladium catalysts were used to generate nucleophilic alkyl
      radicals from alkyl halides, which then directly add onto the arenes. The arene
      scope and the site of alkylation are opposite to those of classical Friedel
      Crafts alkylations, which prefer electron-rich systems.

PMID- 29645327
TI  - Exploring cancer survivors' views of health behaviour change: "Where do you
      start, where do you stop with everything?"
AB  - OBJECTIVE: Physical activity (PA) and a healthy diet can improve the well-being
      of cancer survivors. However, cancer survivors often do not engage in these
      behaviours. This study aimed to explore barriers and facilitators to engaging in
      these behaviours following cancer treatment. METHODS: During the development of a
      Web-based intervention to enhance health-related quality of life in cancer
      survivors, 32 people who had completed treatment for breast, colon, or prostate
      cancer were presented with an intervention for PA and healthy eating. In-depth
      think-aloud and semi-structured interviewing techniques were used to elicit
      perceptions of both behaviours. Data were analysed using thematic analysis.
      RESULTS: Some individuals reported implementing positive health behaviour changes
      to maintain health and prevent recurrence, or to help them to move forward after
      cancer. However, others reported feeling abandoned, and many did not report an
      intention to engage in lifestyle changes. Individuals discussed contextual and
      health-related barriers that were specifically linked to their situation as post
      treatment cancer survivors: individuals described uncertainty about how to
      implement adaptive changes and perceived a lack of support from health care
      providers. Others viewed behaviour change as unnecessary or undesirable, with
      some arguing that non-modifiable factors contributed more to their cancer
      diagnosis than lifestyle-related factors. CONCLUSIONS: For many participants in
      this study, the period that follows treatment for cancer did not represent a
      "teachable moment." A variety of complex and heterogeneous factors appeared to
      impact motivation and may limit cancer survivors from engaging with diet and PA
      changes.

PMID- 29645328
TI  - Potential of Pyridine Amphiphiles as Staphylococcal Nuclease Inhibitor.
AB  - The present study explores the potential of pyridine-based synthetic amphiphiles
      C1 and C2 having 4-carbon and 12-carbon hydrophobic tails, respectively, as
      staphylococcal nuclease inhibitors. UV-visible titration with calf-thymus DNA (CT
      DNA) revealed a hypochromic shift in the absorbance bands of C1 and C2, whereas
      fluorescence titration indicated a reduction in the emission intensity of the
      monomer bands of the amphiphiles. Interaction of deoxyribonuclease I (DNase 1)
      and micrococcal nuclease (MNase) with C1 or C2 led to a decrease in the emission
      intensity of tryptophan at lambda=345 nm along with an increase in the monomer
      emission intensity of C1 and C2 at lambda=375 nm for DNase I and excimer emission
      intensity at lambda=470 nm for both DNase I and MNase. Scatchard's analysis
      indicated superior interaction of C2 with DNase I. Circular dichroism
      spectroscopy revealed major changes in the secondary structures of both DNase I
      and MNase upon interaction with the amphiphiles. A solution-based nuclease assay
      in conjunction with gel electrophoresis indicated amphiphile-mediated protection
      against nuclease-directed DNA cleavage. Interestingly, C2 could render inhibition
      of nuclease present in the culture supernatant of Staphylococcus aureus MTCC 96,
      which highlights the therapeutic prospect of the amphiphile against S. aureus.

PMID- 29645329
TI  - Modulating the Folding Landscape of Superoxide Dismutase 1 with Targeted
      Molecular Binders.
AB  - Amyotrophic lateral sclerosis, or Lou Gehrig's disease, is characterized by motor
      neuron death, with average survival times of two to five years. One cause of this
      disease is the misfolding of superoxide dismutase 1 (SOD1), a phenomenon
      influenced by point mutations spanning the protein. Herein, we used an epitope
      specific high-throughput screen to identify a peptide ligand that stabilizes the
      SOD1 native conformation and accelerates its folding by a factor of 2.5. This
      strategy may be useful for fundamental studies of protein energy landscapes as
      well as designing new classes of therapeutics.

PMID- 29645330
TI  - Current and projected cumulative impacts of fire, drought, and insects on timber
      volumes across Canada.
AB  - Canada's forests are shaped by disturbances such as fire, insect outbreaks, and
      droughts that often overlap in time and space. The resulting cumulative
      disturbance risks and potential impacts on forests are generally not well
      accounted for by models used to predict future impacts of disturbances on forest.
      This study aims at projecting future cumulative effects of four main natural
      disturbances, fire, mountain pine beetle, spruce budworm and drought, on timber
      volumes across Canada's forests using an approach that accounts for potential
      overlap among disturbances. Available predictive models for the four natural
      disturbances were used to project timber volumes at risk under aggressive climate
      forcing up to 2100. Projections applied to the current vegetation suggest
      increases of volumes at risk related to fire, mountain pine beetle, and drought
      over time in many regions of Canada, but a decrease of the volume at risk related
      to spruce budworm. When disturbance effects are accumulated, important changes in
      volumes at risk are projected to occur as early as 2011-2041, particularly in
      central and eastern Canada. In our last simulation period covering 2071-2100,
      nearly all timber volumes in most of Canada's forest regions could be at risk of
      being affected by at least one of the four natural disturbances considered in our
      analysis, a six-fold increase relative to the baseline period (1981-2010). Tree
      species particularly vulnerable to specific disturbances (e.g., trembling aspen
      to drought) could suffer disproportionate increases in their volume at risk with
      potential impacts on forest composition. By 2100, estimated wood volumes not
      considered to be at risk could be lower than current annual timber harvests in
      central and eastern Canada. Current level of harvesting could thus be difficult
      to maintain without the implementation of adaptation measures to cope with these
      disturbances.

PMID- 29645331
TI  - A Genetically Encoded Ratiometric pH Probe: Wavelength Regulation-Inspired Design
      of pH Indicators.
AB  - Mutants of human cellular retinol-binding protein II (hCRBPII) were engineered to
      bind a julolidine retinal analogue for the purpose of developing a ratiometric pH
      sensor. The design relied on the electrostatic influence of a titratable amino
      acid side chain, which affects the absorption and, thus, the emission of the
      protein/fluorophore complex. The ratio of emissions obtained at two excitation
      wavelengths that correspond to the absorption of the two forms of the
      protein/fluorophore complex, leads to a concentration-independent measure of pH.

PMID- 29645332
TI  - Intermolecular sigma-Bond Cross-Exchange Reaction between Cyclopropenones and
      (Benzo)silacyclobutanes: Straightforward Access towards
      Sila(benzo)cycloheptenones.
AB  - Described herein is the first intermolecular sigma-bond exchange reaction between
      the C-C bond of cyclopropenones and C-Si bond of (benzo)silacyclobutanes and it
      proceeds smoothly by treatment with either 1 mol % of a palladium or 2 mol % of a
      nickel catalyst. This reaction constitutes an unprecedented route for the
      synthesis of various sila(benzo)suberones. And it is also the first example of a
      sigma-bond exchange reaction involving cyclopropenones.

PMID- 29645333
TI  - Stabilization of Lewis Acidic AuF3 as an N-Heterocyclic Carbene Complex:
      Preparation and Characterization of [AuF3 (SIMes)].
AB  - Two different reaction routes are described to access the unprecedented
      trifluoridoorganogold(III) complex [AuF3 (SIMes)]. The compound bears the N
      heterocyclic carbene SIMes (1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2
      ylidene) as a ligand for a molecular Lewis acidic AuF3 unit and was characterized
      by NMR spectroscopy as well as X-ray crystallography. Apart from the use of a
      [AuF4 ]- salt as precursor, the strong oxidizing compound AuF3 can be employed
      neat as starting material. The reaction proceeded even in organic solvents in the
      presence of SIMes as the ligand precursor. Decomposition reactions with the
      solvent can, therefore, be prevented by using this strategy.

PMID- 29645334
TI  - Breslow Intermediates from Aromatic N-Heterocyclic Carbenes (Benzimidazolin-2
      ylidenes, Thiazolin-2-ylidenes).
AB  - We report the first generation and characterization of elusive Breslow
      intermediates derived from aromatic N-heterocyclic carbenes (NHCs), namely
      benzimidazolin-2-ylidenes (NMR, X-ray analysis) and thiazolin-2-ylidenes (NMR).
      In the former case, the diamino enols were generated by reaction of the free N,N
      bis(2,6-diisopropylphenyl)- and N,N-bis(mesityl)-substituted benzimidazolin-2
      ylidenes with aldehydes while the dimer of 3,4,5-trimethylthiazolin-2-ylidene
      served as the starting material in the latter case. The unambiguous NMR
      identification of the first thiazolin-2-ylidene-based Breslow intermediate rests
      on double 13 C labeling of both the NHC and the aldehyde component. The acyl
      anion reactivity was confirmed by benzoin formation with excess aldehyde.

PMID- 29645335
TI  - Shell-Isolated Tip-Enhanced Raman and Fluorescence Spectroscopy.
AB  - Tip-enhanced Raman spectroscopy can provide molecular fingerprint information
      with ultrahigh spatial resolution, but the tip will be easily contaminated, thus
      leading to artifacts. It also remains a great challenge to establish tip-enhanced
      fluorescence because of the quenching resulting from the proximity of the metal
      tip. Herein, we report shell-isolated tip-enhanced Raman and fluorescence
      spectroscopies by employing ultrathin shell-isolated tips fabricated by atomic
      layer deposition. Such shell-isolated tips not only show outstanding
      electromagnetic field enhancement in TERS but also exclude interference by
      contaminants, thus greatly promoting applications in solution. Tip-enhanced
      fluorescence has also been achieved using these shell-isolated tips, with
      enhancement factors of up to 1.7*103 , consistent with theoretical simulations.
      Furthermore, tip-enhanced Raman and fluorescence signals are acquired
      simultaneously, and their relative intensities can be manipulated by changing the
      shell thickness. This work opens a new avenue for ultrahigh resolution surface
      analysis using plasmon-enhanced spectroscopies.

PMID- 29645336
TI  - Raman Microspectroscopic Evidence for the Metabolism of a Tyrosine Kinase
      Inhibitor, Neratinib, in Cancer Cells.
AB  - Tyrosine kinase receptors are one of the main targets in cancer therapy. They
      play an essential role in the modulation of growth factor signaling and thereby
      inducing cell proliferation and growth. Tyrosine kinase inhibitors such as
      neratinib bind to EGFR and HER2 receptors and exhibit antitumor activity.
      However, little is known about their detailed cellular uptake and metabolism.
      Here, we report for the first time the intracellular spatial distribution and
      metabolism of neratinib in different cancer cells using label-free Raman imaging.
      Two new neratinib metabolites were detected and fluorescence imaging of the same
      cells indicate that neratinib accumulates in lysosomes. The results also suggest
      that both EGFR and HER2 follow the classical endosome lysosomal pathway for
      degradation. A combination of Raman microscopy, DFT calculations, and LC-MS was
      used to identify the chemical structure of neratinib metabolites. These results
      show the potential of Raman microscopy to study drug pharmacokinetics.

PMID- 29645337
TI  - Enantioselective Formal [3+2] Cycloaddition of Epoxides with Imines under
      Bronsted Base Catalysis: Synthesis of 1,3-Oxazolidines with Quaternary
      Stereogenic Center.
AB  - The formal [3+2] cycloaddition of epoxides and unsaturated compounds is a
      powerful methodology for the synthesis of densely functionalized five-membered
      heterocyclic compounds containing oxygen. Described is a novel enantioselective
      formal [3+2] cycloaddition of epoxides under Bronsted base catalysis. The
      bis(guanidino)iminophosphorane as a chiral organosuperbase catalyst enabled the
      enantioselective reaction of beta,gamma-epoxysulfones with imines, owing to its
      strong basicity and high stereocontrolling ability, to provide enantioenriched
      1,3-oxazolidines having two stereogenic centers, including a quaternary one, in a
      highly diastereo- and enantioselective manner.

PMID- 29645338
TI  - Kinetic Resolution of alpha-Hydroxy-Substituted Oxime Ethers by Enantioselective
      Cu-H-Catalyzed Si-O Coupling.
AB  - A catalyst-controlled enantioselective alcohol silylation by Cu-H-catalyzed
      dehydrogenative Si-O coupling of hydroxy groups alpha to an oxime ether and
      simple hydrosilanes is reported. The selectivity factors reached in this kinetic
      resolution are generally high (s~50), and these reactions thereby provide
      reliable access to highly enantioenriched alpha-hydroxy-substituted oxime ethers.
      The synthetic usefulness of these compounds is also demonstrated.

PMID- 29645339
TI  - Nucleophile Promiscuity of Natural and Engineered Aldolases.
AB  - The asymmetric aldol addition reaction mediated by aldolases is recognized as a
      green and sustainable method for carbon-carbon bond formation. Research in this
      area has unveiled their unprecedented synthetic potential toward diverse, new
      chemical structures; novel product families; and even as a technology for
      industrial manufacturing processes. Despite these advances, aldolases have long
      been regarded as strictly selective catalysts, particularly for nucleophilic
      substrates, which limits their broad applicability. In recent years, advances in
      screening technologies and metagenomics have uncovered novel C-C biocatalysts
      from superfamilies of widely known lyases. Moreover, protein engineering has
      revealed the extraordinary malleability of different carboligases to offer a
      toolbox of biocatalysts active towards a large structural diversity of
      nucleophile substrates. Herein, the nucleophile ambiguity of native and
      engineered aldolases is discussed with recent examples to prove this novel
      concept.

PMID- 29645341
TI  - Effects on the glucagon response to hypoglycaemia during DPP-4 inhibition in
      elderly subjects with type 2 diabetes: A randomized, placebo-controlled study.
AB  - AIMS: Maintainance of glucagon response to hypoglycaemia is important as a
      safeguard against hypoglycaemia during glucose-lowering therapy in type 2
      diabetes. During recent years, DPP-4 (dipeptidyl peptidase-4) inhibition has
      become more commonly used in elderly patients. However, whether DPP-4 inhibition
      affects the glucagon response to hypoglycaemia in the elderly is not known and
      was the aim of this study. METHODS: In a single-centre, double-blind, randomized,
      placebo-controlled crossover study, 28 subjects with metformin-treated type 2
      diabetes (17 male, 11 female; mean age, 74 years [range 65-86]; mean HbA1c, 51.5
      mmol/mol [6.9%]) received sitagliptin (100 mg once daily) as add-on therapy or
      placebo for 4 weeks with a 4-week washout period in between. After each treatment
      period, the subjects underwent a standard breakfast test, followed by a 2-step
      hyperinsulinaemic hypoglycaemic clamp (target 3.5 and 3.0 mmol/L), followed by
      lunch. RESULTS: Glucagon levels after breakfast and lunch, and the glucagon
      response at 3.5 mmol/L, were lower after sitagliptin than after placebo. However,
      the glucagon response to hypoglycaemia at 3.1 mmol/L did not differ significantly
      between the two. Similarly, the noradrenaline, adrenaline and cortisol responses
      were lower with sitagliptin than with placebo at 3.5 mmol/L, but not at 3.1
      mmol/L glucose. Responses in pancreatic polypeptide did not differ between the
      two. CONCLUSIONS: Elderly subjects with metformin-treated type 2 diabetes have
      lower glucagon levels at 3.5 mmol/L glucose, but maintain the glucagon response
      to hypoglycaemia at 3.1 mmol/L during DPP-4 inhibition, which safeguards against
      hypoglycaemia and may contribute to decreasing the risk of hypoglycaemia by DPP-4
      inhibition in this age group.

PMID- 29645340
TI  - Surface Enrichment in Equimolar Mixtures of Non-Functionalized and Functionalized
      Imidazolium-Based Ionic Liquids.
AB  - For equimolar mixtures of ionic liquids with imidazolium-based cations of very
      different electronic structure, we observe very pronounced surface enrichment
      effects by angle-resolved X-ray photoelectron spectroscopy (XPS). For a mixture
      with the same anion, that is, 1-methyl-3-octylimidazolium hexafluorophosphate+1,3
      di(methoxy)imidazolium hexafluorophosphate ([C8 C1 Im][PF6 ]+[(MeO)2 Im][PF6 ]),
      we find a strong enrichment of the octyl chain-containing [C8 C1 Im]+ cation and
      a corresponding depletion of the [(MeO)2 Im]+ cation in the topmost layer. For a
      mixture with different cations and anions, that is, [C8 C1 Im][Tf2 N]+[(MeO)2
      Im][PF6 ], we find both surface enrichment of the [C8 C1 Im]+ cation and the [Tf2
      N]- (bis[(trifluoromethyl)sulfonyl]imide) anion, while [(MeO)2 Im]+ and [PF6 ]-
      are depleted from the surface. We propose that the observed behavior in these
      mixtures is due to a lowering of the surface tension by the enriched components.
      Interestingly, we observe pronounced differences in the chemical shifts of the
      imidazolium ring signals of the [(MeO)2 Im]+ cations as compared to the non
      functionalized cations. Calculations of the electronic structure and the
      intramolecular partial charge distribution of the cations contribute to
      interpreting these shifts for the two different cations.

PMID- 29645344
TI  - Functional and oncological outcomes of open, laparoscopic and robot-assisted
      partial nephrectomy: a multicentre comparative matched-pair analyses with a
      median of 5 years' follow-up.
AB  - OBJECTIVES: To compare outcomes at a 5-year median follow-up among different
      partial nephrectomy (PN) approaches: robot-assisted (RAPN), laparoscopic (LPN)
      and open partial nephrectomy (OPN). PATIENTS AND METHODS: We retrospectively
      analysed 1 308 patients who underwent PN (RAPN, n = 380; LPN, n = 206; OPN, n =
      722) between 2006 and 2012 at one of four academic centres. We performed 1:1:1
      propensity-score-matching adjustment based on confounding variables among groups,
      and 366 patients (122 in each group) were included in the final analysis.
      Survival rates were analysed using the Kaplan-Meier method. RESULTS: The median
      follow-up periods were 60, 59.8 and 64.1 months for RAPN, LPN and OPN,
      respectively. In the matched groups, RAPN resulted in significantly lower mean
      estimated blood loss compared with LPN (P = 0.025) and OPN (P = 0.040), while LPN
      was associated with a longer mean operating time compared with RAPN (P = 0.001)
      and OPN (P = 0.001). The hospital stay was shorter in the RAPN group (P = 0.008).
      Regarding the oncological outcomes, there were no significant differences among
      the three groups in local recurrence rate (P = 0.882), distant metastasis rate (P
      = 0.816) or deaths from cancer (P = 0.779). At latest follow-up, the incidence of
      chronic kidney disease (CKD) upstaging was significantly lower in RAPN compared
      with LPN (20.55% vs 32%; P = 0.035) and OPN (20.5% vs 33.6%; P = 0.038). The 5
      year CKD free-survival rate was significantly higher (78.4%) in the RAPN group
      compared with 58.8% and 65.8% in the LPN and OPN groups, respectively (log-rank P
      = 0.031). CONCLUSIONS: In the present study, RAPN, LPN and OPN had similar local
      recurrence, distant metastasis and cancer-related death rates at a 5-year median
      follow-up. In terms of functional outcomes, RAPN was associated with a lower
      incidence of CKD upstaging compared with OPN and LPN.

PMID- 29645342
TI  - Identifying New Small Proteins in Escherichia coli.
AB  - The number of small proteins (SPs) encoded in the Escherichia coli genome is
      unknown, as current bioinformatics and biochemical techniques make short gene and
      small protein identification challenging. One method of small protein
      identification involves adding an epitope tag to the 3' end of a short open
      reading frame (sORF) on the chromosome, with synthesis confirmed by immunoblot
      assays. In this study, this strategy was used to identify new E. coli small
      proteins, tagging 80 sORFs in the E. coli genome, and assayed for protein
      synthesis. The selected sORFs represent diverse sequence characteristics,
      including degrees of sORF conservation, predicted transmembrane domains, sORF
      direction with respect to flanking genes, ribosome binding site (RBS) prediction,
      and ribosome profiling results. Of 80 sORFs, 36 resulted in encoded synthesized
      proteins-a 45% success rate. Modeling of detected versus non-detected small
      proteins analysis showed predictions based on RBS prediction, transcription data,
      and ribosome profiling had statistically-significant correlation with protein
      synthesis; however, there was no correlation between current sORF annotation and
      protein synthesis. These results suggest substantial numbers of small proteins
      remain undiscovered in E. coli, and existing bioinformatics techniques must
      continue to improve to facilitate identification.

PMID- 29645346
TI  - Identification of a Siglec-F+ granulocyte-macrophage progenitor.
AB  - In recent years multi-parameter flow cytometry has enabled identification of
      cells at major stages in myeloid development; from pluripotent hematopoietic stem
      cells, through populations with increasingly limited developmental potential
      (common myeloid progenitors and granulocyte-macrophage progenitors), to
      terminally differentiated mature cells. Myeloid progenitors are heterogeneous,
      and the surface markers that define transition states from progenitors to mature
      cells are poorly characterized. Siglec-F is a surface glycoprotein frequently
      used in combination with IL-5 receptor alpha (IL5Ralpha) for the identification
      of murine eosinophils. Here, we describe a CD11b+ Siglec-F+ IL5Ralpha- myeloid
      population in the bone marrow of C57BL/6 mice. The CD11b+ Siglec-F+ IL5Ralpha-
      cells are retained in eosinophil deficient PHIL mice, and are not expanded upon
      overexpression of IL-5, indicating that they are upstream or independent of the
      eosinophil lineage. We show these cells to have GMP-like developmental potential
      in vitro and in vivo, and to be transcriptionally distinct from the classically
      described GMP population. The CD11b+ Siglec-F+ IL5Ralpha- population expands in
      the bone marrow of Myb mutant mice, which is potentially due to negative
      transcriptional regulation of Siglec-F by Myb. Lastly, we show that the role of
      Siglec-F may be, at least in part, to regulate GMP viability.

PMID- 29645347
TI  - Does the introduction of prostate multiparametric magnetic resonance imaging into
      the active surveillance protocol for localized prostate cancer improve patient re
      classification?
AB  - OBJECTIVES: To determine whether replacement of protocol-driven repeat prostate
      biopsy (PB) with multiparametric magnetic resonance imaging (mpMRI) +/- repeat
      targeted prostate biopsy (TB) when evaluating men on active surveillance (AS) for
      low-volume, low- to intermediate-risk prostate cancer (PCa) altered the
      likelihood of or time to treatment, or reduced the number of repeat biopsies
      required to trigger treatment. PATIENTS AND METHODS: A total of 445 patients
      underwent AS in the period 2010-2016 at our institution, with a median
      (interquartile range [IQR]) follow-up of 2.4 (1.2-3.7) years. Up to 2014,
      patients followed a 'pre-2014' AS protocol, which incorporated PB, and
      subsequently, according to the 2014 National Institute for Health and Care
      Excellence (NICE) guidelines, patients followed a '2014-present' AS protocol that
      included mpMRI. We identified four groups of patients within the cohort: 'no
      mpMRI and no PB'; 'PB alone'; 'mpMRI +/- TB'; and 'PB and mpMRI +/- TB'. Kaplan
      Meier plots and log-rank tests were used to compare groups. RESULTS: Of 445
      patients, 132 (30%) discontinued AS and underwent treatment intervention, with a
      median (IQR) time to treatment of 1.55 (0.71-2.4) years. The commonest trigger
      for treatment was PCa upgrading after mpMRI and TB (43/132 patients, 29%). No
      significant difference was observed in the time at which patients receiving a PB
      alone or receiving mpMRI +/- TB discontinued AS to undergo treatment (median 1.9
      vs 1.33 years; P = 0.747). Considering only those patients who underwent repeat
      biopsy, a greater proportion of patients receiving TB after mpMRI discontinued AS
      compared with those receiving PB alone (29/66 [44%] vs 32/87 [37%]; P = 0.003).
      On average, a single set of repeat biopsies was needed to trigger treatment
      regardless of whether this was a PB or TB. CONCLUSIONS: Replacing a systematic PB
      with mpMRI +/-TB as part of an AS protocol increased the likelihood of re
      classifying patients on AS and identifying men with clinically significant
      disease requiring treatment. mpMRI +/-TB as part of AS thereby represents a
      significant advance in the oncological safety of the AS protocol.

PMID- 29645345
TI  - Comparison of clinical outcome of hepatic arterial infusion chemotherapy and
      sorafenib for advanced hepatocellular carcinoma according to macrovascular
      invasion and transcatheter arterial chemoembolization refractory status.
AB  - BACKGROUND AND AIM: Sorafenib is the standard treatment for patients with
      advanced hepatocellular carcinoma (HCC) with distant metastasis, unresectable
      HCC, and HCC refractory to transcatheter arterial chemoembolization (TACE) or
      with macroscopic vascular invasion (MVI). Also, hepatic arterial infusion
      chemotherapy (HAIC) has been used for advanced HCC in Southeast and East Asian
      countries. However, clearer information is needed for choosing appropriately
      between these therapies. METHODS: The subjects were 391 HAIC and 431 sorafenibs
      administered at our hospital and related hospitals. In this case, cases that
      satisfy the following three conditions were targeted: (i) no extrahepatic
      metastasis, (ii) Child-Pugh A, and (ii) not having received treatment of both
      HAIC and sorafenib during the course. As a result, 150 cases of HAIC and 134
      cases of sorafenib were analyzed this time. RESULTS: Univariate and multivariate
      analyses were performed for the HAIC and sorafenib groups. TACE refractory status
      and MVI were factors contributing to overall survival (OS). Therefore, this study
      divided all cases according to those variables. The median survival time of MVI
      positive and non-TACE refractory cases was significantly better with HAIC (13
      months) versus sorafenib (6 months). However, in MVI-negative and TACE refractory
      cases, the median survival time of HAIC (8 months) was significantly poorer than
      for sorafenib (20 months). CONCLUSION: Transcatheter arterial chemoembolization
      refractory status with HAIC and MVI with sorafenib were factors for poor
      prognosis. In particular, HAIC was significantly better than sorafenib as primary
      treatment in MVI and non-TACE refractory cases. It is necessary to consider these
      factors in treatment selection.

PMID- 29645348
TI  - Retzius-sparing robot-assisted radical prostatectomy using the Revo-i robotic
      surgical system: surgical technique and results of the first human trial.
AB  - OBJECTIVE: To evaluate the safety and proficiency of the Revo-i(r) robotic
      platform (Meere Company Inc.) in the treatment of prostate cancer (PCa). PATIENTS
      AND METHODS: A prospective study was carried out on 17 patients with clinically
      localized PCa treated between 17 August 2016 and 23 February 2017 at our urology
      department using the Revo-i. Patients underwent Retzius-sparing robot-assisted
      radical prostatectomy (RS-RARP). The primary objective was to describe the RS
      RARP step-by-step surgical technique using the Revo-i. In addition, the safety of
      the Revo-i was assessed according to intra-operative and the postoperative
      complications within 30 days of surgery. Early oncological outcomes were also
      assessed according to surgical margin status and biochemical recurrence (BCR).
      Continence was defined as use of no or only one pad. Surgeons' satisfaction with
      the Revo-i was assessed using the Likert scale. RESULTS: All surgeries were
      completed successfully, with no conversion to open or laparoscopic surgery. The
      median patient age was 72 years. The median docking time, console time,
      urethrovesical anastomosis time and estimated blood loss were 8 min, 92 min, 26
      min and 200 mL, respectively. One patient was transfused intra-operatively as a
      result of blood loss of 1 500 mL. Postoperatively, two patients received blood
      transfusion, and there were no other serious/major complications. The median
      hospital stay was 4 days. At 3 months, four patients had positive surgical
      margins, one patient had BCR, and 15 patients were continent. Most of surgeons
      were satisfied with the Revo-i performance. CONCLUSIONS: The first human study
      for the treatment of patients with localized PCa using the Revo-i robotic
      surgical system was carried out successfully. The peri-operative, early
      oncological and continence outcomes are encouraging. Further prospective studies
      are warranted to support our preliminary results.

PMID- 29645349
TI  - Endoscopic and external approaches for orbital decompression: an analysis of
      trends from a U.S. perspective.
AB  - BACKGROUND: Although the endoscopic approach has been increasingly utilized for a
      variety of sinonasal and skull base pathologies, there has been little inquiry
      into its adoption in the surgical management of orbital disease. Our objective
      was to evaluate nationwide temporal and geographic trends in approaches for
      orbital decompression. METHODS: Data available from the Centers for Medicare and
      Medicaid Services (CMS) were evaluated, focusing on the use of open and
      endoscopic approaches for orbital decompression (CPT codes 67414, 67445, 31292,
      and 31293) among Medicare beneficiaries over a 10-year period. Regional data were
      also analyzed. RESULTS: There were 8047 orbital decompressions billed to Medicare
      from 2007 to 2016. The number of external and endoscopic approaches increased by
      73.0% and 29.2%, respectively, while the number of Medicare beneficiaries
      increased by 29.1%. Endoscopic decompression represented 23.5% of Medicare-billed
      orbital decompressions in 2016 (221 of 939), down from 29.2% in 2007 (171 of
      586). The South had the greatest proportion of decompressions utilizing an
      endoscopic approach (30.2%). CONCLUSION: There has not been a clear movement
      toward the endoscopic approach for orbital decompression, with modest growth when
      compared with external approaches. Potential explanations include the specialty
      exclusive nature of approaches, as well as a lack of consensus; the latter idea
      is further reinforced by geographic variation. High-quality prospective trials
      may clarify the role of endoscopic approaches in these patients.

PMID- 29645351
TI  - A Proteomics Approach to Identify Candidate Proteins Secreted by Muller Glia that
      Protect Ganglion Cells in the Retina.
AB  - The retinal Muller glial cells, can enhance the survival and activity of neurons,
      especially of retinal ganglion cells (RGCs), which are the neurons affected in
      diseases such as glaucoma, diabetes, and retinal ischemia. It has been
      demonstrated that Muller glia release neurotrophic factors that support RGC
      survival, yet many of these factors remain to be elucidated. To define these
      neurotrophic factors, a quantitative proteomic approach was adopted aiming at
      identifying neuroprotective proteins. First, the conditioned medium from porcine
      Muller cells cultured in vitro under three different conditions were isolated and
      these conditioned media were tested for their capacity to promote survival of
      primary adult RGCs in culture. Mass spectrometry was used to identify and
      quantify proteins in the conditioned medium, and osteopontin (SPP1), clusterin
      (CLU), and basigin (BSG) were selected as candidate neuroprotective factors. SPP1
      and BSG significantly enhance RGC survival in vitro, indicating that the survival
      promoting activity of the Muller cell secretome is multifactorial, and that SPP1
      and BSG contribute to this activity. Thus, the quantitative proteomics strategy
      identify proteins secreted by Muller glia that are potentially novel
      neuroprotectants, and it may also serve to identify other bioactive proteins or
      molecular markers.

PMID- 29645350
TI  - Degradation of altered mitochondria by autophagy is impaired in Lafora disease.
AB  - Lafora disease (LD) is a fatal neurodegenerative disorder caused mostly by
      mutations in either of two genes encoding laforin and malin. LD is characterized
      by accumulation of a poorly branched form of glycogen in the cytoplasm of neurons
      and other cells. We previously reported dysfunctional mitochondria in different
      LD models. Now, using mitochondrial uncouplers and respiratory chain inhibitors,
      we have investigated with human fibroblasts a possible alteration in the
      selective degradation of damaged mitochondria (mitophagy) in LD. By flow
      cytometry of MitoTracker-labelled cells and measuring the levels of various
      mitochondrial proteins by western blot, we found in LD fibroblasts a partial
      impairment in the increased mitochondrial degradation produced by these
      treatments. In addition, colocalization of mitochondrial and lysosomal markers
      decreased in LD fibroblasts. All these results are consistent with a partial
      impairment in the induced autophagic degradation of dysfunctional mitochondria in
      LD fibroblasts. However, canonical recruitment of Parkin to mitochondria under
      these conditions remained unaffected in LD fibroblasts, and also in SH-SY5Y cells
      after malin and laforin overexpression. Neither mitochondrial localization nor
      protein levels of Bcl-2-like protein 13, another component of the mitophagic
      machinery that operates under these conditions, were affected in LD fibroblasts.
      In contrast, although these treatments raised autophagy in both control and LD
      fibroblasts, this enhanced autophagy was clearly lower in the latter cells.
      Therefore, the autophagic degradation of altered mitochondria is impaired in LD,
      which is due to a partial defect in the autophagic response and not in the
      canonical mitophagy signalling pathways.

PMID- 29645352
TI  - Efficacy and safety of prostate artery embolization for benign prostatic
      hyperplasia: an observational study and propensity-matched comparison with
      transurethral resection of the prostate (the UK-ROPE study).
AB  - OBJECTIVES: To assess the efficacy and safety of prostate artery embolization
      (PAE) for lower urinary tract symptoms (LUTS) secondary to benign prostatic
      hyperplasia (BPH) and to conduct an indirect comparison of PAE with transurethral
      resection of the prostate (TURP). PATIENTS AND METHODS: As a joint initiative
      between the British Society of Interventional Radiologists, the British
      Association of Urological Surgeons and the National Institute for Health and Care
      Excellence, we conducted the UK Register of Prostate Embolization (UK-ROPE)
      study, which recruited 305 patients across 17 UK urological/interventional
      radiology centres, 216 of whom underwent PAE and 89 of whom underwent TURP. The
      primary outcomes were International Prostate Symptom Score (IPSS) improvement in
      the PAE group at 12 months post-procedure, and complication data post-PAE. We
      also aimed to compare IPSS score improvements between the PAE and TURP groups,
      using non-inferiority analysis on propensity-score-matched patient pairs. The
      clinical results and urological measurements were performed at clinical sites.
      IPSS and other questionnaire-based results were mailed by patients directly to
      the trial unit managing the study. All data were uploaded centrally to the UK
      ROPE study database. RESULTS: The results showed that PAE was clinically
      effective, producing a median 10-point IPSS improvement from baseline at 12
      months post-procedure. PAE did not appear to be as effective as TURP, which
      produced a median 15-point IPSS score improvement at 12 months post-procedure.
      These findings are further supported by the propensity score analysis, in which
      we formed 65 closely matched pairs of patients who underwent PAE and patients who
      underwent TURP. In terms of IPSS and quality-of-life (QoL) improvement, there was
      no evidence of PAE being non-inferior to TURP. Patients in the PAE group had a
      statistically significant improvement in maximum urinary flow rate and prostate
      volume reduction at 12 months post-procedure. PAE had a reoperation rate of 5%
      before 12 months and 15% after 12 months (20% total rate), and a low complication
      rate. Of 216 patients, one had sepsis, one required a blood transfusion, four had
      local arterial dissection and four had a groin haematoma. Two patients had non
      target embolization that presented as self-limiting penile ulcers. Additional
      patient-reported outcomes, pain levels and return to normal activities were very
      encouraging for PAE. Seventy-one percent of PAE cases were performed as
      outpatient or day cases. In contrast, 80% of TURP cases required at least 1 night
      of hospital stay, and the majority required 2 nights. CONCLUSION: Our results
      indicate that PAE provides a clinically and statistically significant improvement
      in symptoms and QoL, although some of these improvements were greater in the TURP
      arm. The safety profile and quicker return to normal activities may be seen as
      highly beneficial by patients considering PAE as an alternative treatment to
      TURP, with the concomitant advantages of reduced length of hospital stay and need
      for admission after PAE. PAE is an advanced embolization technique demanding a
      high level of expertise, and should be performed by experienced interventional
      radiologists who have been trained and proctored appropriately. The use of cone
      beam computed tomography is encouraged to improve operator confidence and
      minimize non-target embolizations. The place of PAE in the care pathway is
      between that of drugs and surgery, allowing the clinician to tailor treatment to
      individual patients' symptoms, requirements and anatomical variation.

PMID- 29645353
TI  - Discovering genes responsible for silk synthesis in Bombyx mori by piggyBac-based
      random insertional mutagenesis.
AB  - Silkworm mutants are valuable resources for both transgenic breeding and gene
      discovery. PiggyBac-based random insertional mutagenesis has been widely used in
      gene functional studies. In order to discover genes involved in silk synthesis, a
      piggyBac-based random insertional library was constructed using Bombyx mori, and
      the mutants with abnormal cocoon were particularly screened. By this means, a
      "thin cocoon" mutant was identified. This mutant revealed thinner cocoon shell
      and shorter posterior silk gland (PSG) compared with the wild type. The messenger
      RNA (mRNA) levels of all the three fibroin genes, including Fib-H, Fib-L and P25,
      were significantly down-regulated in the PSG of mutants. Four piggyBac insertion
      sites were identified in Aquaporin (AQP), Longitudinals lacking protein-like
      (Lola), Glutamyl aminopeptidase-like (GluAP) and Loc101744460. The mRNA levels of
      all the four genes were significantly altered in the silk gland of mutants. In
      particular, the mRNA amount of AQP, a gene responsible for the regulation of
      osmotic pressure, decreased dramatically immediately prior to the spinning stage
      in the anterior silk gland of mutants. The identification of the genes disrupted
      in the "thin cocoon" mutant in this study provided useful information for
      understanding silk production and transgenic breeding of silkworms in the future.

PMID- 29645354
TI  - The price of pain in chronic rhinosinusitis.
AB  - BACKGROUND: Chronic rhinosinusitis (CRS) is associated with productivity losses
      exceeding US$13 billion annually. Although pain is well known to significantly
      affect patient productivity in other diseases, its economic impact on CRS-related
      lost productivity has not been examined. The objective of this study was to
      determine whether CRS-related facial pain correlates with lost productivity in
      patients with CRS. METHODS: Seventy patients with CRS were enrolled in a cross
      sectional investigation. Patients with a history of systemic inflammatory
      disease, ciliary dysfunction, chronic pain syndromes, migraines, and fibromyalgia
      were excluded. Pain was measured using the Brief Pain Inventory Short Form (BPI
      SF) and the Short-Form McGill Pain Questionnaire (SF-MPQ). Presenteeism,
      absenteeism and lost work, and household and overall productivity were assessed.
      Regression analysis was performed to assess potential confounders, including
      depression. RESULTS: Pain as measured with BPI-SF and SF-MPQ total scores
      correlated with all domains of productivity losses. Overall, lost productivity
      was significantly correlated with pain (R range, 0.354-0.485; p < 0.001).
      Presenteeism (reduced work efficiency) had the highest correlation with all of
      the overall pain scores (R range, -0.366 to -0.515; p < 0.001). Lost household
      productivity time was the least affected by pain (R range, 0.267-0.389; p <
      0.05). These correlations remained statistically significant after regression
      analysis, which accounted for depression (p < 0.05). CONCLUSION: A significant
      correlation exists between CRS-related facial pain and productivity losses in
      patients with CRS that is independent of depression. Facial pain has the
      strongest correlation with presenteeism, which is the main driver of productivity
      losses and indirect costs associated with CRS.

PMID- 29645355
TI  - European experience of robot-assisted kidney transplantation: minimum of 1-year
      follow-up.
AB  - OBJECTIVES: To evaluate functional results, graft survival and late complications
      in patients who underwent robot-assisted kidney transplantation (RAKT) and who
      had a minimum of 1 year of follow-up data, and to analyse the correlations
      between surgical data and functional results at a minimum of 1-year
      postoperatively and between renal function in the immediate postoperative period
      and after 1 year. MATERIALS AND METHODS: A common prospectively collected RAKT
      database was created by the European Robotic Urological Section (ERUS) RAKT
      working group, which included eight different European centres. In each centre
      RAKTs were performed with kidneys from living donors. Data on demographic
      variables, surgical results, graft survival, functional outcomes (creatinine and
      estimated glomerular filtration rate [eGFR]) on postoperative days 7 and 30 and
      at 1 year, and late complications were extracted from the common database.
      RESULTS: A total of 147 RAKTs were performed by the ERUS RAKT working group. Of
      the 147 patients, 83 had at least 1-year follow-up (mean [range] 21 [13-27]
      months). Of these 83 patients, 30 were women. The patients' median (range) age
      was 43 (30-75) years, body mass index was 25.3 (20-40) kg/m2 , pre
      transplantation serum creatinine was 517 (198-1 414) MUmol/L and estimated GFR
      (eGFR) was 10 (3-29) mL/min per 1.73 m2 . Of the 83 cases, 46 were pre-emptive.
      The median (range) overall ischaemia time was 116 (53-377) min. The median
      (range) rewarming time was 60 (35-110) min. At 1-year follow-up, the median
      (range) serum creatinine was 131 (66-244) MUmol/L, with a median (range) eGFR of
      57.4 (28-97) mL/min per 1.73 m2 . There was no statistically significant
      difference between functional data at postoperative day 30 and those at 1 year
      for creatinine (P = 0.78) or eGFR (P = 0.91). Regarding the correlation between
      the surgical data and the functional outcomes, the data showed that overall
      operating time and rewarming time did not affect the graft function at 1 year.
      Three cases of graft loss occurred as a result of massive arterial thrombosis
      within the first postoperative week. Late complications comprised one case of
      ureteric stenosis and one case of graft pyelonephritis. No late vascular
      complications or cases of incisional hernia were recorded. CONCLUSION: Findings
      at 1-year follow-up indicate RAKT from a living donor to be a safe procedure in a
      properly selected group of recipients. RAKT was associated with a low
      complication rate and there was maintenance of excellent graft survival and
      function. This is the first and largest study to report functional results after
      RAKT from a living donor with a minimum follow-up of 1 year.

PMID- 29645357
TI  - Triphenylamine-Appended Half-Sandwich Iridium(III) Complexes and Their Biological
      Applications.
AB  - Organometallic half-sandwich IrIII complexes of the type [(eta5 -Cpx
      )Ir(N^N)Cl]PF6 (Cpx : Cp* or its phenyl Cpxph or biphenyl Cpxbiph derivatives;
      N^N: triphenylamine (TPA)-substituted bipyridyl ligand groups) were synthesized
      and characterized. The complexes showed excellent bovine serum albumin (BSA) and
      DNA binding properties and were able to oxidize NADH to NAD+ (NAD=nicotinamide
      adenine dinucleotide) efficiently. The complexes induced apoptosis effectively
      and led to the emergence of reactive oxygen species (ROS) in cells. All complexes
      showed potent cytotoxicity with IC50 values ranging from 1.5 to 7.1 MUm toward
      A549 human lung cancer cells after 24 hours of drug exposure, which is up to 14
      times more potent than cisplatin under the same conditions.

PMID- 29645358
TI  - Co/CoOx Nanoparticles Embedded on Carbon for Efficient Catalysis of Oxygen
      Evolution and Oxygen Reduction Reactions.
AB  - The oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) are
      important electrochemical reactions to realize clean energy technologies. Herein,
      we prepared a hybrid electrocatalyst consisting of Co/CoOx nanoparticles embedded
      in amorphous carbon through the simple pyrolysis of cobalt-based zeolitic
      terephthalate frameworks. The pyrolysis temperature significantly influenced the
      structure morphology and catalytic behavior. Good contact between Co/CoOx and
      amorphous carbon resulted in a high catalytic efficiency. The hybrid obtained
      under pyrolysis temperature of 600  degrees C exhibited the highest performance
      for OER, offering a stable current density of 10 mA cm-2 at 277 mV in basic
      media. Besides good OER behavior, it also showed good ORR performance [onset
      potential: ~0.87 V vs. the reversible hydrogen electrode (RHE), diffusion
      limiting current density: ~4.9 mA cm-2 ]. This work describes a novel and
      efficient catalyst, and greatly expands the scope of low-cost Co-based
      electrocatalysts for various electrochemical reactions without the need for N
      containing ligands.

PMID- 29645359
TI  - Intake of Fatty Fish Alters the Size and the Concentration of Lipid Components of
      HDL Particles and Camelina Sativa Oil Decreases IDL Particle Concentration in
      Subjects with Impaired Glucose Metabolism.
AB  - SCOPE: Intake of long-chain n-3 PUFAs affects the lipoprotein subclass profile,
      whereas the effect of shorter chain n-3 PUFAs remains unclear. We investigated
      the effect of fish and camelina sativa oil (CSO) intakes on lipoprotein
      subclasses. METHODS AND RESULTS: Altogether, 79 volunteers with impaired glucose
      metabolism were randomly assigned to CSO, fatty fish (FF), lean fish (LF), or
      control group for 12 weeks. Nuclear magnetic resonance spectroscopy was used to
      determine lipoprotein subclasses and their lipid components. The average HDL
      particle size increased in the FF group (overall p = 0.032) as compared with the
      control group. Serum concentrations of cholesterol in HDL and HDL2 (overall p =
      0.024 and p = 0.021, respectively) and total lipids and phospholipids in large
      HDL particles (overall p = 0.012 and p = 0.019, respectively) increased in the FF
      group, differing significantly from the LF group. The concentration of
      intermediate-density lipoprotein (IDL) particles decreased in the CSO group
      (overall p = 0.033) as compared with the LF group. CONCLUSION: Our study suggests
      that FF intake causes a shift toward larger HDL particles and increases the
      concentration of lipid components in HDL, which may be associated with the
      antiatherogenic properties of HDL. Furthermore, CSO intake decreases IDL particle
      concentration. These changes may favorably affect cardiovascular risk.

PMID- 29645360
TI  - An Active Palladium Colloidal Catalyst for the Selective Oxidative Heterocoupling
      of (Hetero)Aryl Boronic Acids.
AB  - A highly selective oxidative heterocoupling protocol for (hetero)aryl boronic
      acids with an active palladium colloidal catalyst was developed. The judicious
      choice of electronically different aryl boronic acids made possible such
      couplings under mild conditions, with air as oxidant, while embracing a wide
      substrate scope. This successful approach further allowed the development of a
      unique one-pot sequential oxidative heterocoupling/Suzuki-Miyaura cross-coupling
      tandem process for accessing substituted terphenyls.

PMID- 29645361
TI  - Perioperative analgesia for patients undergoing endoscopic sinus surgery: an
      evidence-based review.
AB  - BACKGROUND: Misuse and diversion of prescription opioids have been critical in
      facilitating the opioid epidemic. Our objective was to perform a systematic
      evidence-based review delineating perioperative regimens (including opioid
      alternatives) evaluated for endoscopic sinus surgery. METHODS: PubMed/MEDLINE,
      Cochrane Library, and EmBase databases were evaluated for studies detailing
      analgesics employed after endoscopic sinus surgery. Studies were assessed for
      level of evidence. Bias risk was evaluated using the Cochrane Bias tool and GRADE
      criteria. Medication, administration, adverse effects, pain scores, and rescue
      analgesic consumption were evaluated. A summary of evidence detailing benefits,
      harm, and cost was prepared. RESULTS: Thirty-two studies encompassing 1812
      patients were included. The GRADE criteria determined the overall evidence to be
      of moderate quality. Perioperative acetaminophen had few adverse events and
      reduced immediate need for opioid rescue after sinus surgery; studies evaluating
      acetaminophen demonstrate a preponderance of benefit over harm. Nonsteroidal anti
      inflammatory drugs (NSAIDs) also reduce postoperative opioid consumption,
      although a small portion of patients undergoing sinus surgery harbor the
      potential for NSAID intolerance. The aggregate level of evidence for studies
      evaluating NSAIDs was grade A, whereas the aggregate grade of evidence for
      several other agents was grade B. CONCLUSION: There is evidence supporting the
      use of NSAIDs and gabapentin for the control of pain after endoscopic sinus
      surgery. Acetaminophen, alpha-agonists, and local anesthetics are also viable
      options for postoperative analgesia. Familiarity with these data is essential to
      facilitate the use of opioid alternatives. Further large-scale, multi
      institutional, randomized trials are needed to provide conclusive recommendations
      for these perioperative analgesics.

PMID- 29645362
TI  - Structural plasticity of the TDRD3 Tudor domain probed by a fragment screening
      hit.
AB  - : As a reader of di-methylated arginine on various proteins, such as histone, RNA
      polymerase II, PIWI and Fragile X mental retardation protein, the Tudor domain of
      Tudor domain-containing protein 3 (TDRD3) mediates transcriptional activation in
      nucleus and formation of stress granules in the cytoplasm. Despite the TDRD3
      implication in cancer cell proliferation and invasion, warheads to block the di
      methylated arginine recognition pocket of the TDRD3 Tudor domain have not yet
      been uncovered. Here we identified 14 small molecule hits against the TDRD3 Tudor
      domain through NMR fragment-based screening. These hits were further cross
      validated by using competitive fluorescence polarization and isothermal titration
      calorimetry experiments. The crystal structure of the TDRD3 Tudor domain in
      complex with hit 1 reveals a distinct binding mode from the nature substrate. Hit
      1 protrudes into the aromatic cage of the TDRD3 Tudor domain, where the aromatic
      residues are tilted to accommodate a sandwich-like pi-pi interaction. The side
      chain of the conserved residue N596 swings away 3.1 A to form a direct hydrogen
      bond with hit 1. Moreover, this compound shows a decreased affinity against the
      single Tudor domain of survival motor neuron protein, but no detectable binding
      to neither the tandem Tudor domain of TP53-binding protein 1 nor the extended
      Tudor domain of staphylococcal nuclease domain-containing protein 1. Our work
      depicts the structural plasticity of the TDRD3 Tudor domain and paves the way for
      the subsequent structure-guided discovery of selective inhibitors targeting Tudor
      domains. DATABASE: Structural data are available in the PDB under the accession
      number 5YJ8.

PMID- 29645363
TI  - Solvent-Mediated Functionalization of Benzofuroxan on Electron-Rich Ruthenium
      Complex Platform.
AB  - An unprecedented reactivity profile of biochemically relevant R-benzofuroxan
      (R=H, Me, Cl), with high structural diversity and molecular complexity on a
      selective {Ru(acac)2 } (acac=acetylacetonate) platform, in conjugation with EtOH
      solvent mediation, is revealed. This led to the development of monomeric [RuIII
      (acac)2 (L1R )] (1 a-1 c; L1R =2-nitrosoanilido derivatives) and dimeric [{RuII
      (acac)2 }2 (L2R )] (2 a-2 b; L2R =(1E,2E)-N1 ,N2 -bis(2-nitrosophenyl)ethane-1,2
      diimine derivatives) complexes in one pot with a change in the metal redox
      conditions. The functionalization of benzofuroxan in 1 and 2 implied in situ
      reduction of N=O to NH- in the former and solvent-assisted multiple N-C coupling
      in the latter. The aforesaid transformation processes were authenticated through
      structural elucidation of representative complexes, and evaluated by their
      spectroscopic/electrochemical features, along with C2 D5 OD labeling and
      monitoring of the impact of substituents (R) in the benzofuroxan framework on the
      product distribution process. The noninnocent potential of newly developed L1 and
      L2 in 1 and 2, respectively, was also probed by spectroelectrochemistry in
      combination with DFT calculations.

PMID- 29645364
TI  - Costs and outcomes of Lynch syndrome screening in the Australian colorectal
      cancer population.
AB  - BACKGROUND AND AIM: Individuals with Lynch syndrome (LS) are at increased risk of
      LS-related cancers including colorectal cancer (CRC). CRC tumor screening for
      mismatch repair (MMR) deficiency is recommended in Australia to identify LS,
      although its cost-effectiveness has not been assessed. We aim to determine the
      cost-effectiveness of screening individuals with CRC for LS at different age-at
      diagnosis thresholds. METHODS: We developed a decision analysis model to estimate
      yield and costs of LS screening. Age-specific probabilities of LS diagnosis were
      based on Australian data. Two CRC tumor screening pathways were assessed (MMR
      immunohistochemistry followed by MLH1 methylation (MLH1-Pathway) or BRAF V600E
      testing (BRAF-Pathway) if MLH1 expression was lost) for four age-at-diagnosis
      thresholds-screening < 50, screening < 60, screening < 70, and universal
      screening. RESULTS: Per 1000 CRC cases, screening < 50 identified 5.2 LS cases
      and cost $A7041 per case detected in the MLH1-Pathway. Screening < 60 increased
      detection by 1.5 cases for an incremental cost of $A25 177 per additional case
      detected. Screening < 70 detected 1.6 additional cases at an incremental cost of
      $A40 278 per additional case detected. Compared with screening < 70, universal
      screening detected no additional LS cases but cost $A158 724 extra. The BRAF
      Pathway identified the same number of LS cases for higher costs. CONCLUSIONS: The
      MLH1-Pathway is more cost-effective than BRAF-Pathway for all age-at-diagnosis
      thresholds. MMR immunohistochemistry tumor screening in individuals diagnosed
      with CRC aged < 70 years resulted in higher LS case detection at a reasonable
      cost. Further research into the yield of LS screening in CRC patients >= 70 years
      is needed to determine if universal screening is justified.

PMID- 29645365
TI  - Preprocedural Ultrasound for Infant Lumbar Puncture: A Randomized Clinical Trial.
AB  - BACKGROUND: Our purpose was to determine the potential effect of preprocedural
      ultrasound (US) to increase lumbar puncture (LP) success compared with standard
      palpation method. Further, we assessed feasibility of and clinician satisfaction
      with a standardized US protocol. METHODS: This prospective, two-arm, parallel
      group randomized trial was conducted in a single-center pediatric emergency
      department. We compared preprocedural US versus palpation method on success with
      infant LPs. Infants less than 3 months of age requiring LP were enrolled. Sixteen
      pediatric emergency medicine physicians with varied US experience were trained to
      conduct the USs to mark interspace locations. Primary outcome was successful LP,
      defined as obtaining a cerebrospinal fluid (CSF) sample on first attempt with <
      1,000 red blood cells per high-powered field (clear CSF). Secondary outcomes
      included clear CSF on any attempt, any CSF on the first attempt, traumatic LP
      proportion, and LP attempt frequency. Feasibility was assessed by comparing
      provider number attempting the LP and procedure duration. Clinician satisfaction
      and sonographer perceptions of US acceptability and impact were assessed.
      RESULTS: Eighty-one patients consented and 80 were analyzed (99%): 40 per group.
      No statistical difference was seen for the primary outcome (p > 0.05) between
      intervention and control groups (difference 3%; 95% confidence interval = -19% to
      24%). There were no statistical differences between intervention and controls
      groups for secondary outcomes including the rate of traumatic LPs, number of
      attempts, and the duration of LP procedure. Most sonographers (84%) strongly
      agreed or agreed that the US protocol was technically easy to perform, well
      tolerated by the patient (94%), well accepted by the family (100%), and well
      accepted by the LP procedural clinicians (99%). In the US group, the majority of
      clinicians who performed the LPs (68.4%) noted that the preprocedural US
      influenced their behavior, most commonly helping with overall visualization at
      the selected interspace (28.9%) or prompting a change in interspace (26.3%
      higher, 5.3% lower). Seventy-seven percent agreed or strongly agreed that they
      would like to use the technique again for their next LP. The mean US duration was
      4.6 minutes. CONCLUSIONS: Preprocedural US by did not improve the rates of first
      attempt success when compared with palpation method. Our results suggest that US
      is feasible and well accepted, with a perceptible impact on care.

PMID- 29645366
TI  - Oxygen Vacancies in ZnO Nanosheets Enhance CO2 Electrochemical Reduction to CO.
AB  - As electron transfer to CO2 is generally considered to be the critical step
      during the activation of CO2 , it is important to develop approaches to engineer
      the electronic properties of catalysts to improve their performance in CO2
      electrochemical reduction. Herein, we developed an efficient strategy to
      facilitate CO2 activation by introducing oxygen vacancies into electrocatalysts
      with electronic-rich surface. ZnO nanosheets rich in oxygen vacancies exhibited a
      current density of -16.1 mA cm-2 with a Faradaic efficiency of 83 % for CO
      production. Based on density functional theory (DFT) calculations, the
      introduction of oxygen vacancies increased the charge density of ZnO around the
      valence band maximum, resulting in the enhanced activation of CO2 . Mechanistic
      studies further revealed that the enhancement of CO production by introducing
      oxygen vacancies into ZnO nanosheets originated from the increased binding
      strength of CO2 and the eased CO2 activation.

PMID- 29645367
TI  - Salivary functions in mastication, taste and textural perception, swallowing and
      initial digestion.
AB  - Saliva exerts multiple functions in relation to the initial digestive processes
      taking place in the upper parts of the gastrointestinal tract. Ingestion of food
      and beverages, in turn, is a strong stimulus for secretion of saliva with a
      differential composition depending on the neuronal stimulation pattern. This
      review paper provides insight into the mechanisms by which saliva acts in
      relation to taste, mastication, bolus formation, enzymatic digestion and
      swallowing. Also, the protective functions of saliva including maintenance of
      dental and mucosal integrity will be discussed as they indirectly influence the
      digestive process. The final part of this study focuses on the implications of
      xerostomia and salivary gland dysfunction on gastrointestinal functions.

PMID- 29645368
TI  - Kutanes Pseudolymphom nach quadrivalenter HPV-Impfung - eine seltene
      Nebenwirkung.

PMID- 29645369
TI  - Patientenzufriedenheit von 1827 Patienten nach verschiedenen
      Rekonstruktionsmethoden im Gesichtsbereich in Abhangigkeit von Alter,
      Defektgrobetae und Lokalisation.
AB  - HINTERGRUND: Nach Tumoroperationen erfolgt ein Defektverschluss mit den fur den
      individuellen Fall optimalen chirurgischen Methoden. Besonders im Kopf-Hals-
      Bereich ist das Ergebnis sehr wichtig. Ziel der retrospektiven Studie war es,
      Rekonstruktionsmethoden von Defekten entsprechend Alter, Lokalisation und
      Grobetae nach funktionellen und asthetischen Gesichtspunkten zu vergleichen.
      PATIENTEN UND METHODIK: Die betroffenen Patienten wurden mittels Fragebogen
      angeschrieben. 1827 Patienten (Alter von 18 bis 92 Jahren, Median: 56 Jahre)
      beurteilten postoperative Probleme, asthetisches sowie funktionelles Ergebnis und
      das Gesamtresultat. Aus der Patientenakte wurden Grobetae und Lokalisation des
      Defektes sowie die Art des Verschlusses dokumentiert. ERGEBNISSE: Die
      Dehnungslappenplastik erhielt bezuglich des Gesamtresultats mit einer sehr guten
      oder guten Bewertung (86 %) das beste Ergebnis. Lappenplastiken und
      Hauttransplantate wurden schlechter beurteilt. Postoperative Beschwerden traten
      signifikant haufiger nach lokalen Lappenplastiken auf. Die Sichtbarkeit der Narbe
      wurde von alteren Patienten bei allen Defektgrobetaen (< 150 mm2 , 150-300 mm2 ,
      > 300 mm2 ) geringer beurteilt als von jungeren. Narben in der zentralen
      Gesichtspartie wurden als sichtbarer wahrgenommen. Geschlecht und Rauchen hatten
      keinen Einfluss. SCHLUSSFOLGERUNGEN: Narben in zentralen Gesichtsregionen werden
      starker wahrgenommen. Altere Patienten beurteilten die Narbenbildung insgesamt
      als unauffalliger. Dehnungslappenplastiken, auch unter Wundrandspannung, fuhren
      zu sehr guten Ergebnissen und einer hohen Patientenzufriedenheit.

PMID- 29645370
TI  - Der subkutan gestielte retroaurikulare Insellappen zur Rekonstruktion von
      Defekten des Cavum conchae.

PMID- 29645371
TI  - Kongresskalender 2018.

PMID- 29645372
TI  - 3rd Science Days of the Austrian Society of Dermatology and Venereology - OGDV
      Forschungstage.

PMID- 29645374
TI  - Multibazillare Lepra mit dem Erscheinungsbild einer Sinusitis und eines
      chronischen, persistierenden Angioodems.

PMID- 29645375
TI  - Nutzen von Mepolizumab bei einer Patientin mit chronischer spontaner Urtikaria.

PMID- 29645376
TI  - Trendveranderungen bei Auslosern des fixen Arzneimittelexanthems: eine 20-jahrige
      Querschnittsstudie in der Turkei.

PMID- 29645377
TI  - Auf dem Weg zu "actionable Health Information": Das wachsende Arsenal der
      Labordiagnostik bei Krebserkrankungen.

PMID- 29645378
TI  - Berufsbedingter subakut-kutaner Lupus erythematodes durch Aubetaentatigkeit.

PMID- 29645379
TI  - Samtig-weiche hyperelastische Haut bei einem jungen Patienten.

PMID- 29645380
TI  - S1 Guidelines - Dermatoses associated with dermal lymphostasis.
AB  - The objective of the present S1 guidelines is to present current knowledge about
      dermatologically relevant diseases associated with localized dermal lymphostasis,
      thus facilitating their early detection, diagnostic workup, and targeted
      treatment. Whenever possible, treatment should be based on stage-appropriate and
      clearly defined algorithms. The numerous issues regarding differential diagnosis
      and treatment clinicians are confronted with in everyday clinical practice seem
      to warrant the publication of up-to-date guidelines. These guidelines focus on
      patients of all age groups and genders exhibiting skin lesions caused by dermal
      lymphostasis. Specific recommendations are provided with respect to the diagnosis
      and differential diagnosis of the various clinical manifestations. In this
      context, comorbid skin diseases such as atopic dermatitis, psoriasis,
      hidradenitis suppurativa, urticaria, and contact dermatitis will be highlighted,
      including their treatment and associated specific risks. Several other relevant
      current guidelines are referenced as regards the distinction from and treatment
      of common cofactors and comorbid conditions.

PMID- 29645381
TI  - Anulares paraneoplastisches bulloses Pemphigoid imitiert lineare IgA-Dermatose
      bei einem 40-jahrigen Patienten.

PMID- 29645382
TI  - Die Geschichte von den beiden Zungenhalften.

PMID- 29645383
TI  - Exanthem, Fieber und Arthralgien bei einer 19-jahrigen Patientin.

PMID- 29645384
TI  - Liquid Biopsy zur Uberwachung von Melanompatienten.
AB  - In den letzten sechs Jahren wurden verschiedene innovative systemische Therapien
      zur Behandlung des metastasierten malignen Melanoms (MM) entwickelt. Die
      konventionelle Chemotherapie wurde durch neuartige Primartherapien abgelost,
      darunter systemische Immuntherapien (Anti-CTLA4- und Anti-PD1-Antikorper;
      Zulassung von Anti-PDL1-Antikorpern erwartet) und Therapien, die gegen bestimmte
      Mutationen gerichtet sind (BRAF, NRAS und c-KIT). Daher stehen die behandelnden
      Arzte neuen Herausforderungen gegenuber, beispielsweise der Stratifizierung von
      Patienten fur geeignete Behandlungen und der Uberwachung von Langzeit-Respondern
      auf Progression. Folglich werden zuverlassige Methoden zur Uberwachung von
      Krankheitsprogression oder Behandlungsresistenz benotigt. Lokalisierte und
      fortgeschrittene Krebserkrankungen konnen zur Bildung zirkulierender Tumorzellen
      und Tumor-DNA (ctDNA) fuhren, die sich in Proben von peripherem Blut nachweisen
      und quantifizieren lassen (Liquid Biopsy). Im Fall von Melanompatienten konnen
      die Ergebnisse von Liquid Biopsy als neuartige pradiktive Biomarker bei
      therapeutischen Entscheidungen hilfreich sein, insbesondere im Zusammenhang mit
      mutationsbasierten zielgerichteten Therapien. Die Herausforderungen bei der
      Anwendung der Liquid Biopsy beinhalten strikte Kriterien fur den Phanotyp der
      zirkulierenden MM-Zellen oder ihrer Fragmente und die Instabilitat von ctDNA im
      Blut. In diesem Ubersichtsartikel diskutieren wir die Beschrankungen der Liquid
      Biopsy hinsichtlich ihrer Anwendung in der Routinediagnostik.

PMID- 29645387
TI  - Nicht IgE-vermittelte Hypersensitivitat auf Macrogol 6000.

PMID- 29645385
TI  - S1-Leitlinie - Dermatosen bei dermaler Lymphostase.
AB  - Das Ziel dieser S1-Leitlinie ist es, aktuelles Wissen uber dermatologisch
      relevante Krankheitsbilder bei lokal begrenzter dermaler Lymphostase an allen
      Lokalisationen des Hautorgans zu vermitteln, um diese fruhzeitig zu erkennen,
      diagnostisch zu sichern und gezielt zu behandeln. Wann immer moglich, sollte
      diese Therapie anhand klar definierter Algorithmen stadiengerecht erfolgen. Die
      im klinischen Alltag haufig auftauchenden differenzialdiagnostischen und
      therapeutischen Fragen lassen eine aktuelle Leitlinie notwendig erscheinen. Diese
      Leitlinie fokussiert auf Patienten jeglichen Alters und Geschlechts mit
      Hautveranderungen, die im kausalen Zusammenhang mit dermaler Lymphostase stehen.
      In konkreten Handlungsempfehlungen werden die Diagnostik und
      Differenzialdiagnostik der verschiedenen Manifestationsformen bei gleichzeitig
      auftretender dermatologischer Komorbiditat wie beispielsweise atopische
      Dermatitis, Psoriasis vulgaris, Acne inversa, Urtikaria, Kontaktekzeme sowie ihre
      Therapien unter Berucksichtigung besonderer Risiken veranschaulicht. Fur die
      Abgrenzung und Behandlung haufiger therapierelevanter Kofaktoren und Komorbiditat
      wird auf mehrere andere hierfur relevante aktuelle Leitlinien verwiesen.

PMID- 29645388
TI  - Schmerzhafte gruppierte erythematose Papeln in segmentaler Anordnung.

PMID- 29645389
TI  - Perichondritis am Ohr eines afghanischen Immigranten.

PMID- 29645390
TI  - OGDV Preistrager stellen sich vor: Der Osterreichische Dermatologenpreis -
      Unilever Preis 2017 ging an Dr. Thomas Kocher aus Salzburg.

PMID- 29645391
TI  - OGDV Preistrager stellen sich vor: Der Wissenschaftspreis der OGDV 2017 ging an
      Dr. rer. nat. Stefan Hainzl und Dr. rer. nat. Patricia Peking aus Salzburg.

PMID- 29645392
TI  - Patient satisfaction in 1,827 patients following various methods of facial
      reconstruction based on age, defect size and site.
AB  - BACKGROUND: Defect coverage following tumor excision requires a case-by-case
      decision as regards the optimal reconstruction technique. In the head and neck
      region in particular, the cosmetic outcome is of major importance. The objective
      of the present study was to compare various reconstruction methods in terms of
      their functional and aesthetic outcome based on patient age, defect size and
      site. PATIENTS AND METHODS: Overall, 1,827 patients (age: 18-92 years, median
      age: 56 years) were contacted. Using a standardized questionnaire, they were
      asked to assess postoperative complications, cosmetic and functional outcome, and
      the overall result of the surgical procedure. In addition, patient records were
      used to collect data on defect size and site as well as the type of surgical
      procedure employed. RESULTS: Rated as very good or good (86 %), defect closure by
      advancement flaps received the highest scores in terms of overall result. Other
      flaps and skin grafts were rated less favorably. Postoperative complications were
      significantly more common after local flaps. Irrespective of defect size (< 150
      mm2 , 150-300 mm2 , > 300 mm2 ), older patients considered the visibility of the
      scar to be less prominent than younger individuals. Scars in the central facial
      region were perceived to be more visible. Gender and smoking habits had no impact
      on the results of the survey. CONCLUSIONS: Scars in the central facial region
      were perceived to be more prominent. Overall, older individuals considered their
      scars to be less conspicuous. Even though they are initially associated with
      greater tension, advancement flaps resulted in very good aesthetic and functional
      results and a high level of patient satisfaction.

PMID- 29645393
TI  - Vernarbende Alopezien.
AB  - Primar vernarbende Alopezien (PVA) werden nach der Klassifikation der North
      American Hair Research Society nach ihrem prominenten entzundlichen Infiltrat in
      vier Gruppen eingeteilt: PVA mit lymphozytarem, neutrophilem, gemischtzelligem
      oder unspezifischem Entzundungsmuster. Der Haarausfall kann subklinisch beginnen
      und langsam fortschreiten, so dass der genaue Erkrankungsbeginn oft schwer
      nachzuvollziehen ist. Die Diagnose wird haufig verzogert gestellt. Wahrend die
      meisten vernarbenden Alopezien bei vollstandiger Auspragung anhand des klinischen
      Bildes klar zugeordnet werden konnen, ist die Diagnosestellung in der Fruhphase
      oder im Endstadium haufig schwierig. Bei Erstvorstellung sollte eine ausfuhrliche
      Anamnese und dermatologische Ganzkorperuntersuchung, inklusive Trichoskopie
      durchgefuhrt werden. In klinisch unklaren Fallen sollte eine Biopsie erfolgen.
      Aufgrund der Seltenheit der PVA gibt es bisher nur eine niedrige Evidenz uber die
      Wirksamkeiten der Vielzahl der verschiedenen angewandten Therapien. Ziele der
      Therapie einer PVA sind, den Haarausfall zu stoppen oder zumindest zu verzogern,
      die klinischen Entzundungszeichen zu reduzieren, weitere Vernarbung zu verhindern
      sowie die subjektiven Symptome zu lindern. Ein Nachwachsen in bereits vernarbten
      Arealen sollte nicht erwartet werden. Eine antientzundliche Therapie mit
      topischen Kortikosteroiden der Klasse III-IV und/oder mit intrakutanen
      intralasionalen Triamcinolonacetonid-Injektionen kommt bei den meisten PVA in
      Betracht. Die Wahl der systemischen Therapie hangt von der Art des
      pradominierenden entzundlichen Infiltrates ab und umfasst
      antimikrobielle/antibiotische oder immunmodulatorische/immunsuppressive Ansatze.
      Psychologische Unterstutzung und Camouflage-Techniken sollten den Patienten
      angeboten werden.

PMID- 29645394
TI  - Cicatricial alopecia.
AB  - In the classification of the North American Hair Research Society, primary
      cicatricial alopecias (PCA) are divided into four groups according to their
      prominent inflammatory infiltrate: PCAs with lymphocytic, neutrophilic, mixed or
      nonspecific cell inflammation pattern. The hair loss can begin subclinically and
      progress slowly so that the exact onset of the disease is often difficult to
      determine. The diagnosis is often delayed. While most forms of cicatricial
      alopecia can be clearly diagnosed based on clinical presentation in the acute
      disease stage, diagnosis can be challenging in the subacute, early or late
      disease stages. At first presentation, a detailed patient history and
      dermatological examination of the body, including trichoscopy, should be
      performed. In clinically unclear cases, a biopsy should be performed. Due to the
      scarcity of primary cicatricial alopecia, there is little evidence on the
      efficacy of the various therapies. The aims of treatment are to stop or at least
      delay hair loss and progression of the scarring process, reduce clinical
      inflammation signs as well as to alleviate subjective symptoms. Hair re-growth in
      already scarred areas should not be expected. Anti-inflammatory treatment with
      topical corticosteroids class III to IV and / or with intracutaneous
      intralesional triamcinolone acetonide injections can be considered in most of the
      primary cicatricial alopecias. The choice of systemic therapy depends on the type
      of predominant inflammatory infiltrate and includes antimicrobial, antibiotic or
      immunomodulating/immunosuppressive agents. Psychological support and camouflage
      techniques should be offered to the patients.

PMID- 29645395
TI  - Tattooentfernung mit Laser: Gibt es bereits Pikosekundenlaser?

PMID- 29645396
TI  - Die Wirksamkeit einer neuen Nagelspange fur die Behandlung von eingewachsenen
      Nageln.
AB  - HINTERGRUND UND ZIELE: Die Behandlung kompliziert eingewachsener Zehennagel ist
      eine Domane der Chirurgie. Allerdings liegen Berichte vor, nach denen alternative
      Therapieformen mit Nagelspangen eine gute Wirksamkeit zeigen. Ziel der
      vorliegenden Studie war es, die Wirksamkeit einer neuen Nagelspange zur
      Behandlung eingewachsener Zehennagel zu untersuchen. PATIENTEN UND METHODEN: Wir
      fuhrten eine retrospektive Studie an Patienten mit eingewachsenen Zehennageln
      durch, die zwischen dem 1. Juni 2015 und dem 30. Mai 2016 im Krankenhaus Wan Fang
      behandelt wurden. Eingewachsene Zehennagel wurden in akut entzundete/infizierte
      (AI) und chronisch dystrophische (CD) Typen eingeteilt. Unter Verwendung des
      Physician Global Assessment (PGA) wurde die Wirksamkeit von Nagelspangen fur die
      beiden Typen von eingewachsenen Zehennageln 1, 2, 3 und 6 Monate nach Beginn der
      Behandlung und wahrend des letzten Arztbesuchs verglichen. ERGEBNISSE: 21
      Patienten (42 Stellen) hatten eingewachsene Zehennagel des CD-Typs; 25 Patienten
      (36 Stellen) hatten eingewachsene Zehennagel des AI-Typs. Von den betroffenen
      Stellen zeigten nach 1, 3 bzw. 6 Monaten 81 %, 94 % bzw. 100 % ein
      ausgezeichnetes oder akzeptables Ergebnis. Die Rezidivrate betrug 10,3 %, die
      Komplikationsrate 7,7 %. Wahrend eingewachsene Zehennagel des AI-Typs in den
      ersten drei Monaten schneller hervorragende Ergebnisse erzielten als CD-Typ
      Nagel, glichen sich die Ergebnisse nach sechs Monaten an. SCHLUSSFOLGERUNGEN:
      Nagelspangen sind eine wirksame therapeutische Option, insbesondere fur
      eingewachsene Zehennagel vom CD-Typ.

PMID- 29645397
TI  - Behandlungsresistente Komedonen.

PMID- 29645398
TI  - Long-term nitrogen fertilization decreases bacterial diversity and favors the
      growth of Actinobacteria and Proteobacteria in agro-ecosystems across the globe.
AB  - Long-term elevated nitrogen (N) input from anthropogenic sources may cause soil
      acidification and decrease crop yield, yet the response of the belowground
      microbial community to long-term N input alone or in combination with phosphorus
      (P) and potassium (K) is poorly understood. We explored the effect of long-term N
      and NPK fertilization on soil bacterial diversity and community composition using
      meta-analysis of a global dataset. Nitrogen fertilization decreased soil pH, and
      increased soil organic carbon (C) and available N contents. Bacterial taxonomic
      diversity was decreased by N fertilization alone, but was increased by NPK
      fertilization. The effect of N fertilization on bacterial diversity varied with
      soil texture and water management, but was independent of crop type or N
      application rate. Changes in bacterial diversity were positively related to both
      soil pH and organic C content under N fertilization alone, but only to soil
      organic C under NPK fertilization. Microbial biomass C decreased with decreasing
      bacterial diversity under long-term N fertilization. Nitrogen fertilization
      increased the relative abundance of Proteobacteria and Actinobacteria, but
      reduced the abundance of Acidobacteria, consistent with the general life history
      strategy theory for bacteria. The positive correlation between N application rate
      and the relative abundance of Actinobacteria indicates that increased N
      availability favored the growth of Actinobacteria. This first global analysis of
      long-term N and NPK fertilization that differentially affects bacterial diversity
      and community composition provides a reference for nutrient management strategies
      for maintaining belowground microbial diversity in agro-ecosystems worldwide.

PMID- 29645399
TI  - Amyloid-beta Peptide Induces Prion Protein Amyloid Formation: Evidence for Its
      Widespread Amyloidogenic Effect.
AB  - Transmissible spongiform encephalopathy is associated with misfolding of prion
      protein (PrP) into an amyloid beta-rich aggregate. Previous studies have
      indicated that PrP interacts with Alzheimer's disease amyloid-beta peptide
      (Abeta), but it remains elusive how this interaction impacts on the misfolding of
      PrP. This study presents the first in vitro evidence that Abeta induces PrP
      amyloid formation at submicromolar concentrations. Interestingly, systematic
      mutagenesis of PrP revealed that Abeta requires no specific amino acid sequences
      in PrP, and induces the misfolding of other unrelated proteins (insulin and
      lysozyme) into amyloid fibrils in a manner analogous to PrP. This unanticipated
      nonspecific amyloidogenic effect of Abeta indicates that this peptide might be
      involved in widespread protein aggregation, regardless of the amino acid
      sequences of target proteins, and exacerbate the pathology of many
      neurodegenerative diseases.

PMID- 29645400
TI  - Evaluation of a new chest physiotherapy technique in dogs with airway fluid
      accumulation hospitalized in an intensive care unit.
AB  - OBJECTIVE: To evaluate the feasibility, benefits, and adverse effects of
      prolonged slow expiration (PSE) and assisted cough (AC) as chest physiotherapy
      (CP) techniques in dogs with airway fluid accumulation. DESIGN: Prospective
      interventional study. SETTINGS: University teaching hospital. ANIMALS:
      Intervention group of 30 client-owned dogs and retrospective control group of 71
      client-owned dogs. INTERVENTIONS: PSE was performed on dogs with evidence of
      airway fluid accumulation, identified based on physical examination and thoracic
      radiographs. AC was performed if spontaneous cough or swallowing were not
      evident. The PSE treatment was performed every 6 hours until normalization of
      respiratory status or hospital discharge. Animals were monitored for respiratory
      distress, discomfort, and SpO2 during the procedure. A retrospective control
      group was identified by computer search. MEASUREMENTS AND MAIN RESULTS: One
      hundred thirty-three sessions of CP were performed on 30 dogs. Discomfort
      frequency during physiotherapy was low (9%). The most commonly used position for
      CP was in lateral recumbency (95%) and this was well tolerated in most cases.
      There was no significant difference in the median SpO2 before and after CP
      sessions (P = 0.24). Sixty percent of sessions had a spontaneous cough or
      swallowing evident, 21% had successful AC performed, and no cough or swallowing
      occurred in the remaining (19%) sessions despite attempts of AC being made. The
      length of hospitalization was significantly longer in the intervention group (6
      days vs 4) (P = 0.02). There was no difference in survival between the
      intervention (76.7%) and the control (57.7%) group (P = 0.055). CONCLUSIONS: PSE
      associated with AC are easily adaptable, well-tolerated techniques in dogs. The
      benefit of CP in dogs with airway fluid accumulation remains to be determined and
      it is hoped that future randomized controlled prospective studies may help answer
      this line of inquiry.

PMID- 29645401
TI  - Phosphine-Catalyzed Activation of Vinylcyclopropanes: Rearrangement of
      Vinylcyclopropylketones to Cycloheptenones.
AB  - We report a phosphine-catalyzed activation of electron-deficient
      vinylcyclopropanes (VCPs) to generate an ambident C5 synthon that is poised to
      undergo consecutive reactions. The utility of the activation is demonstrated in a
      phosphine-catalyzed rearrangement of vinylcyclopropylketones to cycloheptenones
      in good yields with a broad substrate scope. Mechanistic investigations support a
      stepwise process comprising homoconjugate addition, water-assisted proton
      transfer, and 7-endo-trig SN 2' ring closure.

PMID- 29645402
TI  - A Systematic Review and Integration of Concept Analyses of Self-Care and Related
      Concepts.
AB  - PURPOSE: This systematic review identified, synthesized, and integrated concept
      analyses on self-care and related concepts. DESIGN: The guidelines for systematic
      literature reviews of the Joanna Briggs Institute were followed. METHODS: The
      Cumulative Index to Nursing and Allied Health Literature (CINAHL), PubMed,
      PsycINFO, and EMBASE databases were searched for concept analyses published in
      the past 20 years. FINDINGS: A total of 26 concept analyses were identified that
      had been published on self-care, self-care agency, self-monitoring, self
      management, self-management support, symptom management, and self-efficacy.
      Differences and commonalities in the examined literature were identified, and a
      model was delineated, explaining the relations among the various concepts from
      the nursing perspective. CONCLUSIONS: The healthcare literature has broadly
      described self-care and related concepts; however, consensus on the definitions
      remains beyond our reach and should not be expected, due to the different
      perspectives and paradigms from which the concepts are interpreted. From a
      nursing perspective, self-care can be considered a broad concept encompassing the
      other concepts, which describe more specific individual levels of activities and
      processes. CLINICAL RELEVANCE: Nurses are actively involved in disease management
      and self-management support as well as in promoting self-care in healthy and sick
      people. Referring to a model on self-care and related concepts could avoid
      misinterpretations in nursing practice, research, and policy.

PMID- 29645403
TI  - Quality of Author Guidelines in Nursing Journals.
AB  - PURPOSE: The aims of this study were to (a) describe the information provided in
      author guidelines in nursing journals, (b) assess the completeness of this
      information, and (c) identify the extent and types of reporting guidelines used
      in nursing journals. DESIGN: Content analysis of author guidelines for 245
      nursing journals included in the Directory of Nursing Journals maintained at the
      International Academy of Nursing Editors website. METHODS: Using Research
      Electronic Data Capture, data on 19 criteria for completeness were extracted from
      published author guidelines. Additional details about journal requirements, such
      as allowed length of manuscripts and format for the abstract, were also recorded.
      Reliability was established by simultaneous review of 25 journals (10%) by the
      research assistant and a senior member of the research team. FINDINGS: Author
      guidelines were easily accessible at journal websites or through links to
      download the information. A majority (73.5%) had completeness scores of 75% or
      higher; six journals had guidelines that were 100% complete. Half of the journals
      used the American Psychological Association reference style, and 26.3% used the
      American Medical Association style. Less than one fourth had stated requirements
      to use reporting guidelines such as Consolidated Standards of Reporting Trials
      (CONSORT) and Preferred Reporting Items for Systematic Reviews and Meta-Analyses
      (PRISMA). CONCLUSIONS: Author guidelines for nursing journals are generally
      complete and informative. Although specific reporting guidelines such as CONSORT
      and PRISMA improve the accuracy and completeness of manuscripts on various types
      of studies, most nursing journals do not indicate use of these for manuscript
      preparation. Editors who want to improve their author guidelines should use the
      19 criteria for completeness as a gauge for updating and revision. CLINICAL
      RELEVANCE: Nurses rely on the published literature to inform their practice and
      ensure that it is based on evidence. Guidelines for publishing in the scholarly
      literature assist clinicians and scholars to ensure that published articles are
      complete, current, concise, and accurate.

PMID- 29645404
TI  - Children's Perceptions About the Quality of Pediatric Nursing Care: A Large
      Multicenter Cross-Sectional Study.
AB  - INTRODUCTION: This study explored children's perceptions about the quality of
      nursing care and the determinants of their evaluations according to different
      categories of children's ages. DESIGN: Multicenter cross-sectional study carried
      out on 692 pediatric patients in eight large Italian regional hospitals. METHODS:
      We used a validated questionnaire, translated and adapted to the Italian context,
      consisting of 49 items (5-point Likert scale) exploring nurse characteristics,
      nursing activities, and nursing environment. FINDINGS: The mean score of
      children's perceptions of their overall experience of hospitalization was 3.96;
      the nurse characteristics factor obtained the highest score (mean = 3.79), and it
      was in positive correlation with the satisfaction level across different age
      categories: 4 to 6 years, beta = .37; 7 to 11 years, beta = .31; and 12 to 14
      years, beta = .32. CONCLUSIONS: Nurse characteristics is the only significant
      factor contributing to children's satisfaction across the three different age
      categories. CLINICAL RELEVANCE: In pediatric nursing care, it is important to
      emphasize that nurses' personal characteristics and the ability to connect with
      children are essential compared to the ability to perform tasks.

PMID- 29645405
TI  - Outcomes following a negative computed tomography pulmonary angiography according
      to pulmonary embolism prevalence: a meta-analysis of the management outcome
      studies.
AB  - : Essentials Computed tomographic pulmonary angiography (CTPA) is used to exclude
      pulmonary embolism. This meta-analysis explores the occurrence of venous
      thromboembolic events (VTE) after a CTPA. Occurrence of VTE after a negative CTPA
      is ~8% in study subgroups with a prevalence of PE >= 40%. CTPA may be
      insufficient to safely rule out VTE as a stand-alone diagnostic test for this
      subgroup. SUMMARY: Background Outcome studies have reported the safety of
      computed tomographic pulmonary angiography (CTPA) as a stand-alone imaging
      technique to rule out pulmonary embolism (PE). Whether this can be applied to all
      clinical probabilities remains controversial. Objectives We performed a meta
      analysis to determine the proportion of patients with venous thromboembolic
      events (VTE) despite a negative CTPA according to pretest PE prevalence. Methods
      We searched MEDLINE, EMBASE and the Cochrane Library (January 1990 to May 2017)
      for outcome studies recruiting patients with suspected PE using CTPA as a
      diagnostic strategy. The primary outcome was the cumulative occurrence of VTE at
      3 months following a negative CTPA. Results Twenty-two different studies were
      identified. VTE was confirmed in 2.4% of patients (95% CI, 1.3-3.8%) either at
      the time of the index event or in the 3 months follow-up. Subgroup analyses
      suggested that the cumulative occurrence of VTE was related to pretest prevalence
      of PE, as VTE occurred in 1.8% (95% CI, 0.5-3.7%), 1.4% (95% CI, 0.7-2.3%), 1.0%
      (95% CI, 0.5-1.8%) and 8.1% (95% CI, 3.5-14.5%) of subgroups of patients with a
      PE prevalence < 20%, 20-29%, 30-39% and >= 40%, respectively. This was further
      confirmed using meta-regression analysis. Conclusions The negative predictive
      value of CTPA for VTE varies according to pretest prevalence of PE, and is likely
      to be insufficient to safely rule out VTE as a stand-alone diagnostic test
      amongst patients at the highest pretest probability of VTE. Prospective studies
      are required to validate the appropriate diagnostic algorithm for this subgroup
      of patients.

PMID- 29645406
TI  - Modified clot waveform analysis to measure plasma coagulation potential in the
      presence of the anti-factor IXa/factor X bispecific antibody emicizumab.
AB  - : Essentials The activated partial prothrombin time (aPTT) cannot predict the
      activity of emicizumab (Emi). Adjusted clot waveform analyses using a prothrombin
      time (PT)/aPTT initiator were developed. Activity of Emi in the co-presence of
      factor VIII or bypassing agents was quantified. This assay is useful for
      assessing coagulation potential in Emi-treated hemophilia A. SUMMARY: Background
      Emicizumab is an anti-activated factor IX/FX bispecific antibody that mimics
      activated FVIII cofactor function. Emicizumab does not require activation by
      thrombin, and its effect on shortening the activated partial thromboplastin time
      (APTT) is much greater than that of FVIII. Therefore, the APTT has limited
      utility in hemophilia A (HA) patients treated with emicizumab. Aim To evaluate
      the global coagulation potential of emicizumab. Methods Clot waveform analysis
      (CWA) with prothrombin time (PT)/APTT mixed reagents was used to define
      hemostatic monitoring protocols in HA patients. A modified parameter, adjusted
      |min1| (Ad|min1|), was developed. Maximum and minimum percentage transmittance
      were defined as 100% and 0% in the precoagulation and postcoagulation phases,
      respectively. Ad|min1| was calculated as an index of the maximum velocity of the
      coagulation process. Results Ad|min1| obtained with mixed-trigger reagent
      (PT/APTT/buffer, 1 : 15 : 135) in the presence of emicizumab optimally
      corresponded to the conversion rate estimated in animals; 0.2-0.4 IU dL-1
      equivalent FVIII per 1 MUg mL-1 emicizumab). Ex vivo addition of emicizumab to HA
      plasma with or without inhibitors resulted in concentration-dependent increases
      in Ad|min1|, with some individual variations. The addition of various
      concentrations of FVIII to HA plasma mixed with emicizumab resulted in dose
      dependent increases in Ad|min1|. Similarly, mixtures of activated prothrombin
      complex concentrate and emicizumab added to HA plasma resulted in dose-dependent
      increases in Ad|min1|. In contrast, enhanced coagulation potential appeared to be
      better defined by the clot time than by Ad|min1| in experiments using recombinant
      activated FVII. Conclusion The PT/APTT reagent-triggered adjusted CWA could
      provide a useful means of assessing global coagulation potential in emicizumab
      treated HA patients, with enhanced activity neither masking nor being masked by
      FVIII or bypassing agents.

PMID- 29645407
TI  - Child, caregiver, and family factors associated with child dental utilization
      among Mexican migrant families in California.
AB  - OBJECTIVE: To identify associations between child, caregiver, and family-level
      factors and child dental utilization. RESEARCH DESIGN: Cross-sectional oral
      health survey. PARTICIPANTS: Caregivers and one study child (ages 0-17) from
      Mexican migrant families in northern San Diego county, CA (n=142). METHODS:
      Caregivers reported on child's dental care utilization history and related
      factors, including: child (age, gender, dental insurance, source of care,
      believed to have cavities), caregiver (marital status, income, education,
      acculturation level, depressive symptoms), and family cohesion. Descriptive and
      logistic regression models identified predisposing, enabling, and need factors
      associated with child dental utilization during the past year. RESULTS: Most
      (76%) children had visited the dentist in the past year, while 8.6% had never
      been. Child factors (gender, insurance), caregiver factors (education, depressive
      symptoms), and family cohesion were each associated with child dental utilization
      in the bivariate analyses. In the final adjusted model, uninsured children were
      less likely to have a past year dental visit compared to insured children (Odds
      Ratio (OR) = 0.23, 95% Confidence Interval (CI) = 0.06-0.96). Children whose
      caregivers visited the dentist were 4.29 times more likely to visit the dentist
      in the past year (CI=1.36-13.61). Higher caregiver education was positively
      associated with child dental utilization (OR=4.50, CI=1.50-13.55). CONCLUSION:
      Child age and dental insurance, and caregiver education and dental utilization
      history were associated with whether or not a child had a past year dental visit.
      Ensuring child dental coverage and caregiver access to dental care may promote
      regular dental utilization by children.

PMID- 29645408
TI  - Factors associated with Brazilian adolescents' satisfaction with oral health.
AB  - OBJECTIVE: To identify the sociodemographic, clinical and self-reported
      indicators of oral health associated with Brazilian adolescents' satisfaction
      with oral health. METHODS: Secondary data were used following the examination of
      4,231 adolescents, aged 15 to 19 years, participating in a national oral health
      survey (SBBrasil 2010). The independent variables were grouped into demographics,
      predisposition/facilitation, oral health conditions and perceived dental
      treatment need. Satisfaction with oral health was considered the dependent
      variable. Ordinal logistic (multiple) regression models tested the variables in
      sequence (hierarchical), as per the conceptual model, assuming p<=0.05 as the
      criterion for remaining in the model (Wald test). Adjustment of the model was
      evaluated with the Akaike information criterion (AIC) and -2 Log L. RESULTS:
      Participants with perceived treatment need (OR=2.36, 95% CI = 2.14-2.61),
      toothache (OR=1.18, 1.10-1.28), presence of oral impacts on daily performance
      (OIDP) (OR= 1.55, 1.44-1.68), severe and very severe dental aesthetic index (DAI)
      (OR=1.17, 1.08-1.27), were female (OR=1.16, 1.10-1.23), were of black/brown
      ethnicity (OR=1.10, 1.04-1.17), and had caries in anterior (OR=1.20, 1.08-1.32)
      and posterior teeth (OR=1.22, 1.13-1.32) presented lower satisfaction with oral
      health. CONCLUSION: Satisfaction with oral health in Brazilian adolescents is
      linked to a multidimensional structure of factors that include demographic
      aspects, such as gender and ethnic group, self-perception aspects, such as
      perceived treatment need and oral health impact on daily activities, and clinical
      aspects, such as the presence of toothache, severe malocclusion and caries in
      anterior and posterior teeth.

PMID- 29645409
TI  - RISKY SEXUAL BEHAVIOR AMONG OUT-OF-SCHOOL THAI AND NON-THAI YOUTH IN URBAN CHIANG
      MAI, THAILAND.
AB  - Out-of-school youth in Thailand engage in risky sexual behavior thatputs them at
      risk for contracting HIV infection and can have other negative sexualreproductive
      health outcomes. No study has examined risky sexual behaviors andcompared them
      between Thai and non-Thai out-of-school youth. The current studycompares sexual
      risk behavior and HIV testing behavior between out-of-schoolThai and non-Thai
      youth. We conducted face-to-face interviews in this studypopulation in urban
      Chiang Mai during 2014. Participants were recruited throughconvenience sampling
      from two main sources: non-formal education centers(NFECs) and social meeting
      places. We recruited 924 youth, aged 15-24 years, ofwhom 424 (45.9%) were Thai
      and 500 (54.1%) were non-Thai. The majority wereattending NFECs (82.3%). Of the
      sexually experienced participants (57.7%), 75.4%did not use condoms consistently,
      and 50.3% had at least 2 lifetime sexual partners.Among the study participants,
      the Thai studied youth had significantly higherodds of ever having had sex
      (AOR=2.33; 95% CI: 1.56-3.49; p<0.001), having anearlier sexual debut (AOR=5.52;
      95% CI: 2.71-11.25; p<0.001) and having a largernumber of lifetime sexual
      partners (AOR=2.31; 95% CI: 1.37-3.88; p=0.002) thannon-Thai participants. There
      was no significant difference between the Thai andnon-Thai participants in terms
      of having HIV testing. The Thai studied youth weremore likely to engage in risky
      sexual behavior than the non-Thai youth. However,both groups displayed risky
      sexual behaviors. Future research should explore indepththe drivers of risky
      sexual behaviors among both Thai and non-Thai youth.

PMID- 29645410
TI  - MEDIATION EFFECTS OF OVERCOMMITMENT ON EFFORT, REWARD, INSOMNIA, AND WELL-BEING
      AS MODERATED BY GENDER, AGE, AND JOB POSITION.
AB  - This study aimed to detect the mediation effect of over-commitmentbetween
      occupational stress, insomnia, and well-being; and the moderatingrole of gender,
      age and job position are also to be analyzed. One thousand sixhundred eighteen
      valid samples were recruited from electronic manufacturingservice industry in
      Hunan Province, China. All the data were collected by selfratedquestionnaires
      after written consent. This paper introduced Effort-Reward-Insomnia-Well-being
      model, and it was fitted and validated through the structuralequation model
      analysis. The results of single factor correlation analysis indicatedthat the
      coefficients between most of the items and dimensions presented
      statisticalsignificance. The final fitting model had satisfactory global goodness
      of fit(CMIN/DF=3.99, AGFI=0.926, NNFI=0.950, IFI=0.956, RMSEA=0.043). Both of
      themeasurement model and structural model had acceptable path loadings. Effort
      associatedwith insomnia indirectly and related to well-being directly and
      indirectly;reward could have either directly associated with insomnia and well
      being, orindirectly related to them through over-commitment. Covariates as
      gender, ageand position made differences on the association between occupational
      stress andhealth outcomes. Over-commitment had the ability to mediate the
      relationshipsbetween effort, reward, and health outcomes, and mediation effect
      varied fromdifferent working conditions and outcomes under different covariates.

PMID- 29645411
TI  - ENHANCEMENT OF LEARNING ON SAMPLE SIZE CALCULATION WITH A SMARTPHONE APPLICATION:
      A CLUSTER-RANDOMIZED CONTROLLED TRIAL.
AB  - Sample size determination usually is taught based on theory and is difficultto
      understand. Using a smartphone application to teach sample size calculationought
      to be more attractive to students than using lectures only. This studycompared
      levels of understanding of sample size calculations for research studiesbetween
      participants attending a lecture only versus lecture combined with usinga
      smartphone application to calculate sample sizes, to explore factors
      affectinglevel of post-test score after training sample size calculation, and to
      investigateparticipants' attitude toward a sample size application. A cluster
      randomizedcontrolled trial involving a number of health institutes in Thailand
      was carriedout from October 2014 to March 2015. A total of 673 professional
      participantswere enrolled and randomly allocated to one of two groups, namely,
      341 participantsin 10 workshops to control group and 332 participants in 9
      workshops tointervention group. Lectures on sample size calculation were given in
      the controlgroup, while lectures using a smartphone application were supplied to
      the testgroup. Participants in the intervention group had better learning of
      sample sizecalculation (2.7 points out of maximnum 10 points, 95% CI: 24 - 2.9)
      than theparticipants in the control group (1.6 points, 95% CI: 1.4 - 1.8).
      Participants doingresearch projects had a higher post-test score than those who
      did not have aplan to conduct research projects (0.9 point, 95% CI: 0.5 - 1.4).
      The majority of theparticipants had a positive attitude towards the use of
      smartphone applicationfor learning sample size calculation.

PMID- 29645412
TI  - FACTORS RELATED TO TOOTH LOSS AMONG INDUSTRIAL WORKERS IN PHATHUM THANI,
      THAILAND.
AB  - Tooth loss is an important oral health problem among Thai people. Theobjectives
      of this study were to evaluate the prevalence of and factors associatedwith tooth
      loss among Thai industrial workers in order to apply preventive oralhealth
      programs to this population. The study consisted of 1,500 adults workingin Nava
      Nakorn Industrial Estate, Pathum Thani Province, Thailand in 2014.Probability
      proportion to size cluster sampling was used and 16 clusters wereincluded in the
      study. An oral health questionnaire was developed, evaluated forcontent validity
      by experts and then given to participants to fill out. The studypopulation
      consisted of 621 males (41.4%) and 879 females (58.6%) aged between19-25 years.
      The overall prevalence of tooth loss was 62.2% and the major reasonfor tooth loss
      was dental caries (60%). Results from multivariable logistic regressionanalysis
      show that factors associated with tooth loss were: having a historyof scaling or
      tooth cleaning [adjusted odds ratio (AOR)= 2.47; 95% CI: 1.21-4.65],having dental
      caries with exposed pulp (AOR=4.12; 95% CI: 3.26-7.67), havingtooth mobility due
      to periodontal disease (AOR=2.41; 95% CI: 2.71-5.22), havingneeded tooth
      restoration (AOR=1.75; 95% CI: 1.23-2.65), having a history ofmaxillofacial or a
      temporo-mandibular joint accident (AOR=2.13; 95% CI: 1.87-3.23), wearing dentures
      (AOR=2.58; 95% CI: 2.17-6.72), using dental care servicesduring the previous year
      (AOR=2.21; 95% CI: 1.26-4.57), eating snacks and candydaily (AOR=2.14; 95% CI:
      1.82-2.92), having toothache (AOR=2.64; 95% CI: 1.43-3.92), having dental caries
      (AOR=2.23; 95% CI: 1.62-3.27) and having a history oforthodontic treatment
      (AOR=3.61; 95% CI: 1.84-5.68). The Nagelkerke R squaredfor the model was 0.42.
      Our findings suggest several clinical, socio-economic andlifestyle factors are
      associated with tooth loss among these Thai industrial workers.An appropriate
      preventive oral health program targeting this high-risk grouptaking these factors
      into consideration needs to be developed and implementedin this at risk
      population.

PMID- 29645414
TI  - Medicine.

PMID- 29645413
TI  - Remarks on the Change-Of-Type Theory of Disease.

PMID- 29645415
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29645416
TI  - Varieties.

PMID- 29645417
TI  - On the Effect of Local Influences on Spasmodic Asthma.

PMID- 29645418
TI  - Royal College of Surgeons-Conversazione.

PMID- 29645419
TI  - Case of Fatal Hoematemesis, with Abnormal Splenic Vein.

PMID- 29645420
TI  - Report of the Trial of Dr Pritchard for Murder.

PMID- 29645421
TI  - On Paralysis of the Palate in Facial Palsy.

PMID- 29645422
TI  - Report of Clinical Cases, under the Care of Professor Spence, in the Surgical
      Wards of the Royal Infirmary, from July 1863 to October 1864.

PMID- 29645423
TI  - On Some Congenital Deformities of the Human Cranium.

PMID- 29645424
TI  - Remarks on Abortion in the Early Months of Pregnancy.

PMID- 29645426
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29645425
TI  - On the Origin and Circulation of Nerve Force.

PMID- 29645427
TI  - A New Uterine Support.

PMID- 29645428
TI  - University of Edinburgh-Number of Students.

PMID- 29645429
TI  - Remarks on the Retentive Power of the Abdomen.

PMID- 29645431
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29645430
TI  - Note on the Rinderpest.

PMID- 29645432
TI  - University of Edinburgh-Election of Lord Rector.

PMID- 29645434
TI  - Proceedings of the Edinburgh Obstetrical Society.

PMID- 29645433
TI  - Cases Treated in the Barnhill Hospital and Asylum.

PMID- 29645435
TI  - Remarks on the Medical Evidence in Cases of Death by Suffocation: With Reference
      to the Case of Mary Baird or Downie, Reported in the Edinburgh Medical Journal
      for November 1865.

PMID- 29645437
TI  - Account of a Remarkable Outbreak of Enteric Fever.

PMID- 29645436
TI  - Hydatid Tumours of the Liver: Their Dangers, Their Diagnosis, and Their
      Treatment.

PMID- 29645438
TI  - Successful Case of Ovariotomy.

PMID- 29645440
TI  - Surgery.

PMID- 29645439
TI  - Cases of Ovariotomy.

PMID- 29645441
TI  - Note of Experiments Confirmatory of Those of Kuhne on the Non-Existence of Free
      Ammonia in Blood.

PMID- 29645442
TI  - Medical School, Surgeons' Hall.

PMID- 29645443
TI  - Notes on Italian Asylums for the Insane.

PMID- 29645444
TI  - The Mackintosh Case.-Testimonial to Drs Smith and Lowe.

PMID- 29645445
TI  - Professor Czermak.

PMID- 29645446
TI  - Proceedings of the Edinburgh Obstetrical Society.

PMID- 29645447
TI  - Practice of Medicine.

PMID- 29645448
TI  - Influence of the Imagination on the Foetus in Utero.

PMID- 29645449
TI  - On Some Congenital Deformities of the Human Cranium.

PMID- 29645450
TI  - On the Medical Organization of the Army of the Potomac.

PMID- 29645451
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29645452
TI  - A Clinical Lecture on Pneumonia, Delivered Fifty-Three Years Ago.

PMID- 29645453
TI  - Report of the Trial of George Stephen for Murder: At Aberdeen, 18th and 19th
      April 1865.

PMID- 29645455
TI  - Cases Illustrative of the Employment of Acupressure as a Haemostatic Agent.

PMID- 29645454
TI  - On the Facilitation of the First Stage of Labour.

PMID- 29645456
TI  - The Bruce of Grangehill and Falkland Scholarships and Bursaries.

PMID- 29645457
TI  - On the Definition of Insanity Considered Medico-Legally.

PMID- 29645458
TI  - Account of a Reseoloid Exanthem in Malta, during the Autumn of 1864.

PMID- 29645459
TI  - Dr Christison.

PMID- 29645460
TI  - Appointment.

PMID- 29645461
TI  - The Medical Act Amendment Bill.

PMID- 29645462
TI  - Army Medical Department, and Concerning the Late Influx of Medical Candidates.

PMID- 29645463
TI  - Midwifery.

PMID- 29645464
TI  - Report on Physiology.

PMID- 29645465
TI  - Case of Successful Amputation at the Hip-Joint, on Account of Malignant Tumour of
      the Femur.

PMID- 29645466
TI  - The Cholera Morbus in Egypt.

PMID- 29645467
TI  - On Temporary Insanity.

PMID- 29645468
TI  - On the Prevention of Smallpox.

PMID- 29645469
TI  - On Pepsine in Diseases of Children.

PMID- 29645470
TI  - Case of Femoral Aneurism Successfully Treated by Digital Compression in the
      Groin.

PMID- 29645471
TI  - Trial of Mary Baird or Downie for Child-Murder, with Remarks.

PMID- 29645472
TI  - On Uterine Haematocele.

PMID- 29645473
TI  - Elephantiasis of the Leg, Treated by Ligature of the Femoral Artery; Death from
      Pyaemia.

PMID- 29645474
TI  - Excision of One Lateral Half of the Tongue.

PMID- 29645475
TI  - The Cholera in Paris.

PMID- 29645476
TI  - Royal College of Surgeons.

PMID- 29645478
TI  - Medical Students.

PMID- 29645477
TI  - Chlorate of Potass in the Treatment of Ovarian Disease.

PMID- 29645479
TI  - Organic Spirality-The Umbilical Cord.

PMID- 29645480
TI  - Graduation in Medicine at the University of Edinburgh.

PMID- 29645481
TI  - Report of Clinical Cases, under the Care of Professor Spence, in the Surgical
      Wards of the Royal Infirmary, from July 1863 to October 1864.

PMID- 29645482
TI  - Cullen and Gregory upon Change of Type in Inflammation.

PMID- 29645483
TI  - On the Mortality of Childbed as Affected by the Number of the Labour.

PMID- 29645484
TI  - Forfarshire Medical Association.

PMID- 29645485
TI  - Vertical Hemiplegia of the Palate in a Case of Diabetes Mellitus.

PMID- 29645486
TI  - The Address in Surgery.

PMID- 29645488
TI  - Commissions in British Medical Service.

PMID- 29645487
TI  - Notes on the Recent Epidemic in St Petersburg.

PMID- 29645489
TI  - The Address in Medicine.

PMID- 29645490
TI  - British Medical Association.

PMID- 29645491
TI  - Climacteric Insanity in the Male.

PMID- 29645492
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29645493
TI  - Practice of Medicine.

PMID- 29645494
TI  - Royal College of Surgeons of Edinburgh: Abstract of Regulations for the
      Fellowship.

PMID- 29645495
TI  - Is the Dietary Authorized by the Secretary of State, in the "Rules for Prisons in
      Scotland," Sufficient to Bring up the Physical Frame of an Adult Prisoner to the
      Standard of Health and Vigour, and Maintain It There?

PMID- 29645496
TI  - Report of the Morbid Appearances Found in Cows Affected with Rinderpest and Other
      Forms of Epizootic Disease.

PMID- 29645497
TI  - On the Mortality of Childbed as Affected by the Age of the Mother.

PMID- 29645498
TI  - Navy Medical Department.

PMID- 29645499
TI  - On Certain Positions of the Head as a Cause of Syncope.

PMID- 29645500
TI  - List of Hospitals, Dispensaries, Etc., in Connexion with the Medical Schools of
      Scotland.

PMID- 29645502
TI  - Royal College of Physicians of Edinburgh: Regulations Regarding the Fellowship
      and Membership of the College.

PMID- 29645501
TI  - The Chief Medical Schools of the Continent.

PMID- 29645504
TI  - Faculty of Physicians and Surgeons, Glasgow: Abstract of Regulations for the
      Election and Admission of Fellows.

PMID- 29645503
TI  - The Cholera in France.

PMID- 29645505
TI  - Egyptian Theory as to the Origin of Cholera.

PMID- 29645506
TI  - Army Medical Department.

PMID- 29645507
TI  - Proceedings of the Edinburgh Obstetrical Society.

PMID- 29645508
TI  - Case of Traumatic Rupture of the Uterus; Gastrotomy Thirty Hours after the
      Accident.

PMID- 29645510
TI  - Army Medical School.

PMID- 29645509
TI  - Remarks on a Case of Heightened Reflex Action Treated by Calabar Bean.

PMID- 29645511
TI  - On Acute Yellow Atrophy of the Liver.

PMID- 29645512
TI  - Information Regarding Medical Education and Examinations.

PMID- 29645513
TI  - Graduation Address to the Gentlemen Who Obtained the Degree of M.D. in the
      University of Edinburgh, 1st August 1865.

PMID- 29645514
TI  - Army Medical School.

PMID- 29645516
TI  - Proceedings of the Edinburgh Obstetrical Society.

PMID- 29645515
TI  - Leprosy, Ancient and Modern; with Notes Taken during Recent Travel in the East.

PMID- 29645517
TI  - Case Illustrating the Supposed Connexion of Aphasia (Loss of the Cerebral Faculty
      of Speech) with Right Hemiplegia, and Lesion of the External Left Frontal
      Convolution of the Brain.

PMID- 29645519
TI  - From Abroad.-The Stomatoscope-Respiratory Therapeutics-Popular Lectures on
      Medical Subjects.

PMID- 29645518
TI  - Notes on Some Points in the Administration of Chloroform.

PMID- 29645520
TI  - Clinical Inquiries into the Influence of the Nervous System on the Production and
      Prevention of Dropsies, and on the Means and Methods of Successful Treatment.

PMID- 29645521
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29645522
TI  - Observations on the Arrested Twin Development of Jean Battista Dos Santos, Born
      at Faro in Portugal, in 1846.

PMID- 29645523
TI  - Thermometric Observations on the Fevers of Children.

PMID- 29645524
TI  - Midwifery.

PMID- 29645525
TI  - Lunacy Acts (Scotland) Amendment Bill.

PMID- 29645526
TI  - Correspondence.

PMID- 29645527
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29645528
TI  - Ligature of the Femoral Artery for the Thirty-Fifth Time, with Remarks on the
      Treatment of Aneurism.

PMID- 29645529
TI  - Notes on the Prison Dietaries in Scotland.

PMID- 29645530
TI  - Disease of the Maxillary Antrum, Involving the Brain.

PMID- 29645531
TI  - Case of Intussusception, Terminating in Sloughing and Discharge of the
      Intussuscepted Portion of Intestine; and Recovery.

PMID- 29645532
TI  - On Malformations of the Organs of Generation. Second Series. Foetation in a
      Rudimentary Uterine Cornu.

PMID- 29645533
TI  - On Rupture of the Heart.

PMID- 29645534
TI  - Surgery.

PMID- 29645535
TI  - Proceedings of the Edinburgh Obstetrical Society.

PMID- 29645536
TI  - Vital Statistics of Iceland and Reykjavik during the Last Decennium.

PMID- 29645537
TI  - Proceedings of the Edinburgh Obstetrical Society.

PMID- 29645538
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29645540
TI  - Conversazione of the Royal College of Surgeons.

PMID- 29645539
TI  - Case of Bronchocele and Haemorrhagic Villosities of the Bladder, with Dissections
      of the Tumour.

PMID- 29645541
TI  - On the Action of Medicinal Preparations of Iron on the Teeth.

PMID- 29645542
TI  - Royal College of Physicians of Edinburgh.

PMID- 29645543
TI  - Cases of Ovariotomy.

PMID- 29645544
TI  - Monument to the Late Dr Cullen.

PMID- 29645546
TI  - The New Meat-Preserving Process.

PMID- 29645545
TI  - Where Should Typhus Be Treated?

PMID- 29645547
TI  - Midwifery.

PMID- 29645548
TI  - Case of Death While under the Influence of Chloroform.

PMID- 29645549
TI  - On a Case of Acute Atrophy of the Kidneys and Liver in a Pregnant Woman.

PMID- 29645550
TI  - On the Relative Mortality from Injuries and Burns on the Trunk of the Body, above
      and below the Level of the Diaphragm.

PMID- 29645551
TI  - On the Treatment of Virulent and Zymotic Diseases.

PMID- 29645553
TI  - Questions at the Second Examination for the Degree of Bachelor of Medicine,
      Oxford, December 1865.

PMID- 29645552
TI  - Some Statistics of Idiocy.

PMID- 29645555
TI  - Practice of Medicine.

PMID- 29645554
TI  - On Dilatation of the Perinaeum.

PMID- 29645556
TI  - On Paracentesis Thoracis in the Treatment of Pleural Effusions, Acute and
      Chronic.

PMID- 29645557
TI  - Purpura Haemorrhagica in Children.

PMID- 29645559
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29645558
TI  - Medical News.

PMID- 29645561
TI  - Proceedings of the Edinburgh Obstetrical Society.

PMID- 29645560
TI  - The Harveian Discourse: On the Life and Character of Dr Alison.

PMID- 29645562
TI  - The Convolutions of the Human Cerebrum Topographically Considered.

PMID- 29645563
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29645565
TI  - Proceedings of the Edinburgh Obstetrical Society.

PMID- 29645564
TI  - A Plea for Criminal Epileptics.

PMID- 29645566
TI  - Researches on the Daily Excretion of Urea in Typhus Fever, with Remarks.

PMID- 29645568
TI  - A Lyons Surgeon on English Surgery.

PMID- 29645567
TI  - On Certain Causes Affecting the Origin of Disease in Large Towns.

PMID- 29645569
TI  - The Trichina Disease.

PMID- 29645570
TI  - On Insanity Caused by Injuries to the Head and by Sunstroke.

PMID- 29645571
TI  - Practice of Medicine.

PMID- 29645573
TI  - Cholera in Paris.

PMID- 29645572
TI  - Address on the Recent Progress of Chemistry.

PMID- 29645574
TI  - Professors of the Medical School of Ohio.

PMID- 29645575
TI  - Scientific Report on the Trichina.

PMID- 29645577
TI  - Glasgow Medico-Chirurgical Society.

PMID- 29645576
TI  - Proceedings of the Edinburgh Obstetrical Society.

PMID- 29645578
TI  - Medical Candidates for the Army Medical Service.

PMID- 29645580
TI  - On Encysted Serous Pelvic Effusions Following Puerperal Inflammation.

PMID- 29645579
TI  - Medical Jurisprudence.

PMID- 29645581
TI  - Traumatic Idiocy.

PMID- 29645582
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29645583
TI  - On the Galvano-Puncture of Aneurisms.

PMID- 29645584
TI  - Correspondence.

PMID- 29645585
TI  - On the Conjoined Influence of the Nervous System and of Constitutional Tissue
      Changes in the Production of Dropsies, and on the Various Methods of Treatment
      Applicable Thereto.

PMID- 29645586
TI  - The Action of Fungi in the Production of Disease.

PMID- 29645587
TI  - On Amputation at the Knee.

PMID- 29645589
TI  - Commissions in British Medical Service.

PMID- 29645588
TI  - The New Pharmacopoeia.

PMID- 29645590
TI  - Army Medical Department.

PMID- 29645591
TI  - The College of Surgeons and the Medical Council.

PMID- 29645592
TI  - Treatment of Parkinsonian States by Juster's Method: Report of Twenty-Three
      Cases.

PMID- 29645594
TI  - The Action of Quinine Dihydrochloride on the Intestine.

PMID- 29645593
TI  - Dundee Doctors in the Sixteenth Century.

PMID- 29645596
TI  - Inverted Position in Children's Drawings: Report of Two Cases.

PMID- 29645595
TI  - A Progressive Vascular Osteodystropha Fibrosa.

PMID- 29645597
TI  - Toxic Goitre and Some Complications.

PMID- 29645599
TI  - Synovial Cysts at the Wrist.

PMID- 29645598
TI  - Chloroform Poisoning : Its Biological Significance.

PMID- 29645600
TI  - Auricular Fibrillation Associated with a Mitral Stenotic Murmur.

PMID- 29645601
TI  - The Proper Use of Phenolbarbital in the Treatment of the Epilepsies.

PMID- 29645602
TI  - The Surgery of Toxic Goitre.

PMID- 29645603
TI  - The Diagnostic Investigation of the Abdomen.

PMID- 29645604
TI  - An Unusual Buccal Tumour.

PMID- 29645605
TI  - Dundee Doctors in the Sixteenth Century.

PMID- 29645606
TI  - Coincident Brain Tumour in Twins.

PMID- 29645607
TI  - Auditory Hallucinations Provoked by Intracranial Tumours.

PMID- 29645608
TI  - The Present Status of Convalescent Serum Therapy.

PMID- 29645610
TI  - Nervous and Mental Reactions to Veronal: With Report of a Case of Chronic Veronal
      Poisoning.

PMID- 29645609
TI  - The Qualitative Determination of the Potency of Liver Extract, with Some Remarks
      on Its Possible Mode of Action.

PMID- 29645612
TI  - Arteriography.

PMID- 29645611
TI  - Notes.

PMID- 29645613
TI  - Syphilis Congenita Vera.

PMID- 29645615
TI  - A Curious Colo-Uterine Anomaly.

PMID- 29645614
TI  - Thyroidectomy in Mentally Disturbed Patients with Exophthalmic Goitre, with
      Report of Twelve Cases in Which the Psychosis Was Relieved by Operation.

PMID- 29645616
TI  - Valedictory Address.

PMID- 29645618
TI  - The Symptomatology of Tumours of the Temporal Lobe.

PMID- 29645617
TI  - The Alkali-Reserve of the Blood in Relation to the Van Den Bergh Bilirubin Test.

PMID- 29645619
TI  - Intracranial Tumours among Mental Hospital Patients, with Special Attention to
      the Tumours of the Glioma Series.

PMID- 29645620
TI  - Note on the Pain Sensations Which Accompany Deep Punctures.

PMID- 29645621
TI  - Bronchial Carcinoma.

PMID- 29645622
TI  - Congenital Absence of the Gall-Bladder.

PMID- 29645623
TI  - Recent Advances in the Treatment and Prophylaxis of Leprosy.

PMID- 29645625
TI  - Delayed Traumatic Kyphosis.

PMID- 29645624
TI  - Clinical Phenomena Associated with Depressions, Anxieties, and Other Affective or
      Mood Disorders.

PMID- 29645627
TI  - Post-Hernial Fibrous Stricture of the Small Intestine.

PMID- 29645626
TI  - Acidified Milk for Infant Feeding.

PMID- 29645628
TI  - Case of Intestinal Lipoma.

PMID- 29645630
TI  - Notes.

PMID- 29645629
TI  - Pulmonary Chondroma.

PMID- 29645631
TI  - Essential Nerve-Sheath Tumours.

PMID- 29645632
TI  - Fracture of the Sternum.

PMID- 29645633
TI  - Surgical Treatment of Carotid Ectasia.

PMID- 29645634
TI  - Traumatic Ulnar Neuritis.

PMID- 29645635
TI  - Inhalation of a Head of Grass.

PMID- 29645636
TI  - On the Separation of the Kyogenic Hormone from Human Placenta.

PMID- 29645637
TI  - Observations upon the Vascularity of the Human Occipital Lobe during Visual
      Activity.

PMID- 29645638
TI  - Benign Epitheliomata and Ossification.

PMID- 29645639
TI  - OEsophageal Obstruction by Rotation.

PMID- 29645640
TI  - Encephalitis by Direct Contagion.

PMID- 29645641
TI  - The Absorption and Excretion of Iron by the Intestines and the Nutritional and
      Therapeutic Value of Its Salts.

PMID- 29645643
TI  - Cystinuria and Cystine Calculi.

PMID- 29645642
TI  - Leprosy at Marseille.

PMID- 29645644
TI  - The Medical Treatment of Surgical Tuberculosis and Allied Conditions.

PMID- 29645646
TI  - Notes.

PMID- 29645645
TI  - The Importance of Psychological Insight for the Medical Profession.

PMID- 29645647
TI  - Metatarsal Osteochondritis.

PMID- 29645648
TI  - Cutaneous Digital Actinomycosis.

PMID- 29645649
TI  - Ulnar Paresis in Congenital Dislocation of the Head of the Radius.

PMID- 29645650
TI  - Gastric Ulcer in the New-Born.

PMID- 29645652
TI  - Birth Haemorrhages and Heredity.

PMID- 29645651
TI  - Sarcoma of the Ileum.

PMID- 29645653
TI  - The Operative Treatment of Syringomyelia.

PMID- 29645654
TI  - Transient Lateral Perimalleolar OEdema.

PMID- 29645655
TI  - On the Reactivation of the Senile Testis of the Rat by Means of Injections of
      Gonadotrope Hormones.

PMID- 29645656
TI  - The Nature of the Cancer Process.

PMID- 29645658
TI  - Ankle-Clonus: The Distinction of the Organic and Functional Varieties.

PMID- 29645657
TI  - The General Medical Council: Its Functions and Powers.

PMID- 29645660
TI  - Arteriosclerotic Parkinsonism.

PMID- 29645659
TI  - Caecal Submucous Lipoma.

PMID- 29645661
TI  - A Maxillary Chordoma.

PMID- 29645662
TI  - Accessory Ossicles at Hip-Joint.

PMID- 29645664
TI  - The Treatment of Asthma with Ephedrine.

PMID- 29645663
TI  - The Clinical Significance of Cardiac Asthma.

PMID- 29645665
TI  - Primary Sarcoma of the Great Omentum.

PMID- 29645666
TI  - Operation in Atlanto-Epistrophic Luxation.

PMID- 29645667
TI  - Mumps-Meningitis.

PMID- 29645668
TI  - The Education of the Public in Health Matters, with Special Reference to the Work
      of the National Association for the Prevention of Tuberculosis.

PMID- 29645669
TI  - Tuberculosis of the Congenitally Atrophic Kidney.

PMID- 29645670
TI  - The Prognostic Value of the Blood Sedimentation Test in Tuberculosis.

PMID- 29645671
TI  - Tracheo-Bronchial Cyst.

PMID- 29645672
TI  - The Relation between Glandular and Pulmonary Tuberculosis.

PMID- 29645673
TI  - Difficulties in Assessing the Capacity for Work of Ex-Sanatorium Patients.

PMID- 29645674
TI  - Occurrence of the Bovine-Type Tubercle Bacillus in Pulmonary Tuberculosis: Its
      Role in Pathogenesis.

PMID- 29645676
TI  - Malignant Cavitation of the Lung.

PMID- 29645675
TI  - Implantation Preputial Tuberculosis.

PMID- 29645678
TI  - Diffuse Nodular Pulmonary Syphilis.

PMID- 29645677
TI  - Clinical Meeting.

PMID- 29645679
TI  - The Leucocytic Reaction to Tuberculosis: Its Value in Prognosis.

PMID- 29645680
TI  - Tuberculous Thyreoiditis.

PMID- 29645681
TI  - Notes.

PMID- 29645682
TI  - Inoculation of Calf with Human Tubercle Bacillus.

PMID- 29645685
TI  - Nasopharyngeal Chondroma.

PMID- 29645683
TI  - Pubic Tuberculous Osteitis.

PMID- 29645684
TI  - Microbic Dissociation, with Special Reference to Certain Acid-Fast Bacilli.

PMID- 29645687
TI  - Abdominal Lithopaedion Simulating an Ovarian Tumour.

PMID- 29645686
TI  - The Experimental Production of Post-Operative Abscess of the Lung.

PMID- 29645688
TI  - Venous Pressure in Heart Disease.

PMID- 29645689
TI  - The Mechanism of Cicatricial Contraction in the Brain.

PMID- 29645690
TI  - Active Immunisation against Diphtheria and Scarlatina.

PMID- 29645691
TI  - Symptomatology of a Group of Frontal Lobe Lesions.

PMID- 29645692
TI  - Pain in the Back.

PMID- 29645693
TI  - Sympathectomy for Traumatic Facial Paralysis.

PMID- 29645694
TI  - Notes.

PMID- 29645695
TI  - Some Observations on Blood Grouping.

PMID- 29645696
TI  - Notes.

PMID- 29645697
TI  - Central Diaphyseal Staphylococcal Abscess in an Adult.

PMID- 29645698
TI  - The Immortality of Animal Tissues and Its Significance.

PMID- 29645700
TI  - Middle-Ear Carcinoma.

PMID- 29645699
TI  - Synthalin in Diabetes Mellitus.

PMID- 29645701
TI  - Vasomotor Tumentia.

PMID- 29645702
TI  - Archibald Pitcairne 1652-1713.

PMID- 29645703
TI  - Genetical Aspects of Natural Immunity and Disease Resistance.

PMID- 29645704
TI  - Total Cystectomy for Vesical Carcinoma.

PMID- 29645705
TI  - Forced Grasping and Groping.

PMID- 29645706
TI  - Syphilis of the Bladder.

PMID- 29645707
TI  - Recurring Cervical Chondroma.

PMID- 29645708
TI  - The Treatment of Varicose Ulceration by Intravenous Injections of Quinine.

PMID- 29645709
TI  - Tuberculosis of the Penis.

PMID- 29645710
TI  - Plexiform Neuroma of the Eyelid.

PMID- 29645711
TI  - The Etiology of Tumour Growth from the Evolution Standpoint.

PMID- 29645712
TI  - Erratum: Clinical Pathology.
AB  - [This corrects the article on p. 425 in vol. 35.].

PMID- 29645713
TI  - The "Krukenberg" Tumour.

PMID- 29645715
TI  - Notes.

PMID- 29645714
TI  - Tuberculous Infection in Industrial School Children.

PMID- 29645716
TI  - Cocaine Intoxication and Poisoning in Local Anaesthesia.

PMID- 29645717
TI  - Some Problems of Rheumatic Infections.

PMID- 29645718
TI  - Criminal Abortion by Perchloride of Mercury.

PMID- 29645719
TI  - Clinical Meeting.

PMID- 29645720
TI  - An Unusual Utilisation of a Fascial Graft.

PMID- 29645721
TI  - Fracture-Dislocation of the Talus. Two Cases and Their Mechanism Described.

PMID- 29645722
TI  - Transmission of Tubercle Bacilli to the Child in Utero.

PMID- 29645723
TI  - On the Signs of, and Tests for, Drunkenness.

PMID- 29645724
TI  - Tuberculous Ulceration of the Lower Lip.

PMID- 29645725
TI  - Intranasal Encephalocele.

PMID- 29645726
TI  - Periarterial Sympathectomy by the Application of Ammonia.

PMID- 29645727
TI  - Cancer of the Stomach Mistaken for an Enlarged Spleen.

PMID- 29645729
TI  - Acute Enteric Cholecystitis in a Child.

PMID- 29645728
TI  - Recent Experiences of Intracranial Surgery.

PMID- 29645730
TI  - Congenital Defect of Abdominal-Wall Muscles.

PMID- 29645731
TI  - Subcutaneous Glomal Tumours: Painful Subcutaneous Nodule: Les Angioneuromyomes
      Arteriels. (P. Masson).

PMID- 29645732
TI  - Congenital Talipes and Lumbar Pachymeningitis.

PMID- 29645733
TI  - Sialolithiasis.

PMID- 29645734
TI  - Sir James Wylie, Bart., M.D., 1768-1854: A Medical Adventurer.

PMID- 29645735
TI  - Metastatic Carcinoma of the Central Nervous System.

PMID- 29645736
TI  - Torsion of the Testis.

PMID- 29645738
TI  - Primary Sarcoma of the Spleen.

PMID- 29645737
TI  - Notes.

PMID- 29645739
TI  - Medicine in Edinburgh.

PMID- 29645741
TI  - Subcortical Epilepsy.

PMID- 29645740
TI  - Clinical Contribution to Drug Addiction: The Struggle for Cure and the Conscious
      Reasons for Relapse.

PMID- 29645742
TI  - Consecutive Tests by the Fractional Method of Gastric Analysis.

PMID- 29645743
TI  - Medical Education in Scotland.

PMID- 29645744
TI  - Carcinoma of the Breast.

PMID- 29645745
TI  - Nodular Non-Tuberculous Pulmonary Sclerosis.

PMID- 29645746
TI  - Recurrent Spontaneous Pneumothorax.

PMID- 29645747
TI  - Notes.

PMID- 29645749
TI  - Foreign Body in a Pregnant Uterus.

PMID- 29645748
TI  - "Stream-Lines" in the Portal Vein: Their Influence on the Selective Distribution
      of Blood in the Liver.

PMID- 29645750
TI  - An Unusual Lipoma.

PMID- 29645751
TI  - Rupture of the Stomach in an Infant.

PMID- 29645752
TI  - Treatment of Cancer of the Cervix during Pregnancy.

PMID- 29645754
TI  - Ureteral Papillomata.

PMID- 29645753
TI  - The Examination of the Gastric Contents as an Aid to the Diagnosis of Carcinoma
      of the Stomach.

PMID- 29645755
TI  - Congenital Hypertrophy of the Neck of the Bladder.

PMID- 29645756
TI  - The Correlations of Graves' Disease and Thyroiditis.

PMID- 29645757
TI  - Ligature of the Inferior Vena Cava.

PMID- 29645758
TI  - Cobra Venom.

PMID- 29645759
TI  - Congenital Duodenal Obstruction.

PMID- 29645760
TI  - The Control of Diphtheria: A Plea for Active Immunisation of the Pre-School
      Child.

PMID- 29645761
TI  - Post-Traumatic Osteodystrophy at Joints.

PMID- 29645762
TI  - Some Problems in the Growth and Developmental Mechanics of Bone.

PMID- 29645763
TI  - Corrections.
AB  - [This corrects the article on p. 261 in vol. 41.].

PMID- 29645764
TI  - Primary Cancer of the Lung: Its Incidence and Pathology.

PMID- 29645765
TI  - Clinical Studies in the Pathology of Bone. No. IV.-A Plated Fracture.

PMID- 29645766
TI  - Scarlet Fever.

PMID- 29645767
TI  - Ramisection in Perforating Ulcer.

PMID- 29645769
TI  - Role of the Sympathetic Nervous System in Melancholia.

PMID- 29645768
TI  - The Mental Element in Crime and Criminals.

PMID- 29645771
TI  - Ovarian Dermoid in a Child.

PMID- 29645770
TI  - Valedictory Address.

PMID- 29645772
TI  - Notes.

PMID- 29645773
TI  - The Adreno-Genital Syndrome: An Illustrative Case with Special Reference to Its
      Relation to Cushing's New Pituitary Syndrome.

PMID- 29645774
TI  - Post-Traumatic Decalcification.

PMID- 29645775
TI  - Familial Voluntary Digital Dorsiflexion.

PMID- 29645776
TI  - Congenital Mesial Sinus of the Nose.

PMID- 29645777
TI  - The Mental Element in Crime and Criminals.

PMID- 29645778
TI  - Lumbar Puncture in Some Head Injuries.

PMID- 29645779
TI  - Notes.

PMID- 29645780
TI  - The Preparation of Catgut for Surgical Use.

PMID- 29645781
TI  - Coagulation Treatment of Phlebectasia.

PMID- 29645783
TI  - Processus Vermiformis Duplex.

PMID- 29645782
TI  - Contacts of the Law with Medical Practice.

PMID- 29645784
TI  - Chondromatosis of the Elbow.

PMID- 29645785
TI  - The Relation of the Peripheral Lymphatic System to the Spinal Cord.

PMID- 29645786
TI  - Some Problems in the Growth and Developmental Mechanics of Bone.

PMID- 29645788
TI  - Neurovasomotor Disturbance from Impaction of a Sequestrum in the Mastoid Air
      Sinus.

PMID- 29645787
TI  - Perspectives in Physiology.

PMID- 29645789
TI  - Morning Pain in Frontal Sinusitis.

PMID- 29645791
TI  - Correction.
AB  - [This corrects the article on p. 293 in vol. 41.].

PMID- 29645790
TI  - Renal Efficiency Testing: The Urea Concentration Range in Diagnosis and Prognosis
      of Kidney Inefficiency.

PMID- 29645792
TI  - Silica in Relation to Pulmonary Disease.

PMID- 29645793
TI  - Phrenic Evulsion in the Treatment of Pulmonary Tuberculosis.

PMID- 29645794
TI  - Demonstration of Growths of Tubercle Bacilli.

PMID- 29645795
TI  - Impressions from a Recent Personal Study of Tuberculosis Work in the United
      States of America.

PMID- 29645796
TI  - Demonstration Illustrating the Comparative Value of Certain Media in the Culture
      of Tubercle Bacilli.

PMID- 29645797
TI  - Tuberculous Disease of the Middle Ear and Mastoid.

PMID- 29645798
TI  - The Detection of Tubercle Bacilli in the Blood Stream in Pulmonary Tuberculosis.

PMID- 29645800
TI  - Problems of Research in Tuberculosis.

PMID- 29645799
TI  - Tuberculosis in Relation to Eye Disease.

PMID- 29645801
TI  - Some Aspects of Tuberculosis of the Nervous System. (With Special Reference to
      Tuberculomata).

PMID- 29645802
TI  - Clinical Meeting.

PMID- 29645803
TI  - Clinical Studies in the Pathology of Bone. No. V.-An Epidural Abscess.

PMID- 29645804
TI  - The Treatment of Hypochromic Anaemia with Soluble Ferrous Salts.

PMID- 29645805
TI  - Pregnancy at Six Years of Age.

PMID- 29645806
TI  - The Motive Function of Lymph-Nodes.

PMID- 29645807
TI  - The Mental Element in Crime and Criminals.

PMID- 29645808
TI  - Scoliosis-Paraplegia.

PMID- 29645810
TI  - Sex-Differences in the Gall-Bladder.

PMID- 29645809
TI  - Prognosis in Mammary Carcinoma: In Relation to Grading and Treatment.

PMID- 29645811
TI  - Radiography of the Lymph-Vascular System.

PMID- 29645813
TI  - Congenital Pseudarthrosis of the Tibia.

PMID- 29645812
TI  - Extensive Burns and Scalds.

PMID- 29645815
TI  - Alcoholic Polyneuritis.

PMID- 29645814
TI  - Acrodysplasia: Type: Syndactylic Oxycephaly.

PMID- 29645816
TI  - Gastric Syphilis.

PMID- 29645817
TI  - Solitary Osseous Lipoid Granulomatosis.

PMID- 29645818
TI  - The Teaching of the Neuroses to Medical Students.

PMID- 29645819
TI  - Primary Lymphogranuloma of the OEsophagus.

PMID- 29645820
TI  - Fat Necrosis in the New-Born.

PMID- 29645821
TI  - Marble-Bone Disease.

PMID- 29645823
TI  - Cocainization of the Pharynx.

PMID- 29645822
TI  - Pneumonia and Other Common Respiratory Conditions in the New-Born: A Clinical
      Study.

PMID- 29645824
TI  - Foot Disorders and Resistant Eczematous Ringworm.

PMID- 29645826
TI  - Playing Cards and Microorganisms.

PMID- 29645825
TI  - A Histological Study of the Normal Mamma in Relation to Tumour Growth: II.-The
      Mature Gland in Pregnancy and Lactation.

PMID- 29645827
TI  - Parotid Ephidrosis.

PMID- 29645828
TI  - Salivary Fistulae.

PMID- 29645830
TI  - Pancreatic Cyst.

PMID- 29645829
TI  - Recurrence of Ringworm Infection of the Feet.

PMID- 29645831
TI  - Epidermomycosis.

PMID- 29645832
TI  - Intravenous Injection of Alcohol in Suppurative Pulmonitis.

PMID- 29645833
TI  - Tobacco Amblyopia.

PMID- 29645834
TI  - Innervation of the Amnion.

PMID- 29645835
TI  - Sir Edward Sharpey-Schafer and His Contributions to Neurology.

PMID- 29645836
TI  - Lipoblastic Sarcomatosis.

PMID- 29645837
TI  - Familial Haemorrhagic Telangiectasis.

PMID- 29645838
TI  - A Case of Congenital Short Neck Showing the Klippel-Feil Syndrome.

PMID- 29645840
TI  - Consecutive Traumatism of the Lunate Bones.

PMID- 29645839
TI  - Observations on Blood Pressure in Healthy Adult Males.

PMID- 29645841
TI  - Rickety Osteodystrophy.

PMID- 29645843
TI  - The Surgery of High Blood Pressure.

PMID- 29645842
TI  - Clinical Meeting.

PMID- 29645844
TI  - Lipiodol and the Lung.

PMID- 29645845
TI  - Lingual Lymphangeioma.

PMID- 29645847
TI  - Embolic Aneurysm in Endocarditis.

PMID- 29645846
TI  - Embolectomy.

PMID- 29645848
TI  - The Teaching of the Neuroses to Medical Students.

PMID- 29645850
TI  - Intravascular Migration of Missiles.

PMID- 29645849
TI  - The Specific Effect of Ascorbic Acid on the Anaemia of Scurvy.

PMID- 29645851
TI  - Medical Education in Scotland.

PMID- 29645853
TI  - Pneumokoniosis and Carcinoma.

PMID- 29645852
TI  - Notes.

PMID- 29645855
TI  - Mediastinal Reticulosarcoma.

PMID- 29645854
TI  - Progeria.

PMID- 29645857
TI  - Multiple Calcifications and Parathyreoidectomy.

PMID- 29645856
TI  - Notes.

PMID- 29645858
TI  - Labiobuccal Tuberculosis.

PMID- 29645859
TI  - Acute Osteomyelitis of the Ribs.

PMID- 29645860
TI  - Cobra Venom in Carcinoma.

PMID- 29645862
TI  - Medicine in Early Greek Mythology.

PMID- 29645861
TI  - A Histological Study of the Normal Mamma in Relation to Tumour Growth: II.-The
      Mature Gland in Pregnancy and Lactation.

PMID- 29645863
TI  - Arterial Obliteration from Crutch-Pressure.

PMID- 29645865
TI  - Gastro-OEsophageal Intussusception.

PMID- 29645864
TI  - Glandular Cheilitis.

PMID- 29645866
TI  - Progressive Facial Dystrophy.

PMID- 29645867
TI  - Accessory Denticle in the Eyelid.

PMID- 29645868
TI  - Carcino-Sarcoma : A Study of the Microscopic Anatomy and Meaning of a Peculiar
      Cancer.

PMID- 29645869
TI  - Multiple Cavernous Angeiomata.

PMID- 29645870
TI  - Treatment of Acute Rheumatism.

PMID- 29645871
TI  - Large Accessory Air-Sinuses.

PMID- 29645872
TI  - Notes.

PMID- 29645873
TI  - Rheumatic Heart Disease: Its Nature, Course and Prevention.

PMID- 29645874
TI  - Forensic Medicine.

PMID- 29645875
TI  - Cases Illustrative of the Operation for Femoral Hernia.

PMID- 29645876
TI  - Statistics.

PMID- 29645877
TI  - Practical Remarks on the Treatment of the Various Forms of Dyspepsia.

PMID- 29645878
TI  - On the Electrical Apparatus in Torpedo, Gymnotus, Malapterurus, and Raia.

PMID- 29645879
TI  - Valedictory Address to the Newly Made Medical Graduates of the University of
      Edinburgh, 1st August, 1855.

PMID- 29645881
TI  - Resignation of Professor Alison.

PMID- 29645880
TI  - The Month.

PMID- 29645882
TI  - Opening of an Institution for the Treatment of Idiocy in Edinburgh.

PMID- 29645884
TI  - Case of a Gentleman Who Was Born Deaf and Dumb, and Subsequently Became Insane.

PMID- 29645883
TI  - Scarlet Fever Occurring Twice in the Same Person.

PMID- 29645885
TI  - Surgery of the War in China.

PMID- 29645886
TI  - Epidemics-Hygiene, etc., etc.

PMID- 29645887
TI  - On the Os Sacrum Considered as Forming Part of the Vault of the Pelvis, and on
      Its Function in the Development of the Lateral Expansion of That Cavity.

PMID- 29645888
TI  - On the Local Treatment of Erysipelas with Gutta Percha.

PMID- 29645890
TI  - Medico-Legal Investigation-Child Murder.

PMID- 29645889
TI  - Lecture on the Lamina Spiralis of the Cochlea.

PMID- 29645891
TI  - Cases of Homicidal and Accidental Suffocation, with Remarks.

PMID- 29645892
TI  - The Earl Grey Street Murder.

PMID- 29645893
TI  - Medico-Legal Observations on Manual Strangulation and Death by External Violence,
      with Experiments and Illustrative Cases.

PMID- 29645894
TI  - Inaugural Lecture.

PMID- 29645896
TI  - The Month.

PMID- 29645895
TI  - Sudden Death in a Case in Which Chloroform Was Being Administered.

PMID- 29645897
TI  - The Influence of Vaccination on the Rate of Mortality in France.

PMID- 29645899
TI  - Introductory Lecture.

PMID- 29645898
TI  - On the Communicability of Cholera by Dejections.

PMID- 29645900
TI  - Surgery.

PMID- 29645901
TI  - Diseases of the Spinal Cord and Its Membranes.

PMID- 29645902
TI  - Case of Imputed Murder by Manual Strangulation; with Observations.

PMID- 29645903
TI  - A Case of Supposed Impermeable Stricture of the Urethra Cured by Dilatation, with
      Remarks.

PMID- 29645904
TI  - Lecture on the Retina.

PMID- 29645905
TI  - Medicine.

PMID- 29645906
TI  - Varieties.

PMID- 29645907
TI  - The Month.

PMID- 29645909
TI  - Midwifery.

PMID- 29645908
TI  - Practical Remarks on the Treatment of the Various Forms of Dyspepsia.

PMID- 29645910
TI  - Quarterly Report of Cases Occurring at the Edinburgh Eye-Infirmary.

PMID- 29645911
TI  - Midwifery.

PMID- 29645912
TI  - On the Electrical Apparatus in Torpedo, Ymnotus, Malapterurus, and Raia.

PMID- 29645913
TI  - Conversazione by the Royal College of Physicians to the Officers of the Channel
      Fleet.

PMID- 29645914
TI  - Preliminary Examination Papers for the Double Qualification Conferred by the
      Royal Colleges of Physicians and Surgeons of Edinburgh.

PMID- 29645915
TI  - Notes on the Hospitals of Munich.

PMID- 29645916
TI  - Notice of the Revaccination of Children at the Orphan Hospital.

PMID- 29645917
TI  - Preliminary Examination Papers-Second Series.

PMID- 29645918
TI  - Quarterly Report of Cases Occurring at the Edinburgh Eye Infirmary, 140, George
      Street.

PMID- 29645920
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29645919
TI  - Practice of Medicine.

PMID- 29645921
TI  - General Council of Medical Education and Registration.

PMID- 29645923
TI  - Varieties.

PMID- 29645922
TI  - Report on the Causes of Death among the Assured of the Scottish Widows' Fund Life
      Assurance Society, for the Period from 1st January 1853 to 1st January 1860.

PMID- 29645924
TI  - Case of Leucocythemia.

PMID- 29645925
TI  - Medical Jurisprudence.

PMID- 29645926
TI  - Proceedings of the Edinburgh Obstetrical Society.

PMID- 29645927
TI  - Case of Chronic Internal Abscess of the Lower Jaw.

PMID- 29645929
TI  - Medicine.

PMID- 29645928
TI  - Remarks on Sayre's Splint for Morbus Coxarius.

PMID- 29645930
TI  - Varieties.

PMID- 29645931
TI  - Notes on Certain Feigned Diseases of Soldiers, and on Crime and Desertion in the
      Army.

PMID- 29645932
TI  - Report of the Missionary Hospital in the Western Suburbs of Canton, for 1859-60.

PMID- 29645933
TI  - Case of Abscess of the Larynx.

PMID- 29645934
TI  - Erratum: Delirium Tremens.
AB  - [This corrects the article on p. 305 in vol. 6.].

PMID- 29645935
TI  - On the Use of Calomel in the Removal of Insects in Sores.

PMID- 29645936
TI  - Clinical Report on the Diseases of Women; with Observations.

PMID- 29645937
TI  - Surgery.

PMID- 29645938
TI  - On Acupressure.

PMID- 29645939
TI  - The Radical Cure of Hernia.

PMID- 29645940
TI  - Anatomy.

PMID- 29645941
TI  - University of Edinburgh-Meeting of the General Council.

PMID- 29645942
TI  - Quarterly Return of Births, Deaths, and Marriages.

PMID- 29645943
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29645944
TI  - Report by Dr Weisse, at the Celebration of the 25th Anniversary of the Nicholas
      Sick Children's Hospital in St Petersburgh, 6th December, 1859.

PMID- 29645945
TI  - Preliminary Examination of the Royal Colleges of Physicians and Surgeons of
      Edinburgh, for the Double Qualification.

PMID- 29645946
TI  - Case of Intestinal Worms Terminating Fatally.

PMID- 29645947
TI  - Case of Traumatic Spreading Gangrene, after Severe Compound Fracture of the Leg,
      for Which Amputation beneath the Trochanters Was Performed, and the Arteries
      Secured by Four Acupressure Needles: The Femoral Artery, at Its Giving off the
      Profunda Branch, Was Relieved from Pressure at the Forty-Ninth Hour after the
      Operation: With Recovery; and Remarks.

PMID- 29645948
TI  - Periscope of Otology.

PMID- 29645949
TI  - Upon the Causes, Prevention, and Treatment of Afterpains.

PMID- 29645950
TI  - On Sacro-Pubic Hernia, Otherwise Known as Prolapsus Uteri.

PMID- 29645951
TI  - On a New Antiseptic and Antineuralgic Agent.

PMID- 29645953
TI  - A Case of Cerebro-Spinal Meningitis. Recovery.

PMID- 29645952
TI  - Fatal Case of Ague, with Delirium and Coma during the Paraxysms Due to Cirrhotic
      Kidney.

PMID- 29645954
TI  - Clinical Notes.

PMID- 29645956
TI  - Periscope of Ophthalmology.

PMID- 29645955
TI  - Forfarshire Medical Association.

PMID- 29645957
TI  - On Cleft Palate and Incisor Teeth: An Instance of Heredity.

PMID- 29645958
TI  - Occasional Periscope of Dermatology.

PMID- 29645959
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29645960
TI  - Report of the Royal Maternity and Simpson Memorial Hospital for the Quarter from
      1st February to 30th April 1880.

PMID- 29645961
TI  - Meetings of Societies.

PMID- 29645962
TI  - Monthly Retrospect of Obstetrics and Gynaecology.

PMID- 29645963
TI  - Some of the Uses of Oil of Turpentine.

PMID- 29645964
TI  - On the Alleged Synclitic Movement of the Foetal Head.

PMID- 29645966
TI  - Medical News.

PMID- 29645965
TI  - Cases of Puerperal Fever Treated by the Muriated Tincture of Iron.

PMID- 29645967
TI  - Meetings of Societies.

PMID- 29645968
TI  - Upon the Causes, Prevention, and Treatment of Afterpains.

PMID- 29645969
TI  - Periscope of Syphilology.

PMID- 29645970
TI  - Monthly Retrospect of Obstetrics and Gynaecology.

PMID- 29645972
TI  - On Rotheln, Rubeola, or German Measles.

PMID- 29645971
TI  - Puberty and Adolescence Medico-Psychologically Considered.

PMID- 29645973
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29645974
TI  - Notes of a Case of a Rare Form of Elephantiasis.

PMID- 29645975
TI  - Occasional Periscope of Dermatology.

PMID- 29645976
TI  - Note on the Mode in Which Compensation Is Established in Cases of Aortic
      Incompetence.

PMID- 29645977
TI  - Periscope of Otology.

PMID- 29645978
TI  - On the Riviera, Madeira, the Canary Islands, and Davos, with Reference to Their
      Climate for Consumptive Invalids.

PMID- 29645979
TI  - Cases of Carcinoma of the Female Pelvic Organs in Professor Simpson's Wards
      during the Current Session.

PMID- 29645980
TI  - Army Medical School.

PMID- 29645982
TI  - Navy Medical Department.

PMID- 29645981
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29645984
TI  - Meetings of Societies.

PMID- 29645983
TI  - Indian Medical Service.

PMID- 29645985
TI  - Information Regarding Medical Education and Examinations.

PMID- 29645986
TI  - Periscope of Syphilology.

PMID- 29645987
TI  - On Axis-Traction Forceps.

PMID- 29645988
TI  - Notes on Two Cases of Spina Bifida in the Cervical Region.

PMID- 29645990
TI  - Medical News.

PMID- 29645989
TI  - Clinical Notes.

PMID- 29645991
TI  - Notes of a Case of Abscess in Abdominal Cavity.

PMID- 29645992
TI  - Periscope of Otology.

PMID- 29645993
TI  - Remarks on Obstetrics.

PMID- 29645994
TI  - List of Hospitals, Dispensaries, etc., in Connexion with the Medical Schools of
      Scotland.

PMID- 29645995
TI  - Preliminary Examinations for the Diplomas of the Royal Colleges of Physicians and
      Surgeons of Edinburgh.

PMID- 29645996
TI  - Medical Schools of Scotland, 1880-81.

PMID- 29645997
TI  - Army Medical Department.

PMID- 29645998
TI  - Report of and Observations upon Two Cases of Puerperal Septicaemia.

PMID- 29645999
TI  - 1880. Address to Students of Medicine.

PMID- 29646000
TI  - The Hygiene of the Infectious Fevers.

PMID- 29646001
TI  - Erratum.
AB  - [This corrects the article on p. 236 in vol. 26.].

PMID- 29646002
TI  - Tubercular Leprosy.

PMID- 29646003
TI  - Remarks on Obstetrics.

PMID- 29646004
TI  - Monthly Retrospect of Obstetrics and Gynaecology.

PMID- 29646005
TI  - Dystocia from Coccygeal Ankylosis.

PMID- 29646006
TI  - A Case of Extra-Uterine Pregnancy, Rupture, and Death from Haemorrhage, with
      Results of Post-Mortem Examination.

PMID- 29646007
TI  - Medical News.

PMID- 29646008
TI  - Notes of a Case of Physometra.

PMID- 29646009
TI  - Case of Spontaneous Umbilical Haemorrhage.

PMID- 29646010
TI  - Periscope of Ophthalmology.

PMID- 29646011
TI  - Case of Placenta Praevia Terminating Spontaneously.

PMID- 29646012
TI  - Case of Delivery through a Scoliotic Pelvis.

PMID- 29646013
TI  - On Diseases of the Andaman Islands.

PMID- 29646014
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29646015
TI  - The Hygiene of the Infectious Fevers.

PMID- 29646016
TI  - Occasional Periscope of Dermatology.

PMID- 29646018
TI  - Notes on an Outbreak of Enteric Fever.

PMID- 29646017
TI  - Periscope of Ophthalmology.

PMID- 29646019
TI  - The Examination of the Pulse.

PMID- 29646020
TI  - Introductory Address, Delivered at the Opening of the Edinburgh Medical School,
      on 25th October 1880.

PMID- 29646021
TI  - Monthly Report of the Progress of Therapeutics.

PMID- 29646022
TI  - Bladder-Drainage.

PMID- 29646023
TI  - The Parasitic Fungi of the Human Ear: Etiology. Prophylaxis, Treatment,
      Applications to General Therapeutics.

PMID- 29646024
TI  - Ectopia Renalis.

PMID- 29646025
TI  - Case of Needle in the Urethra Extracted through Posterior Wall.

PMID- 29646026
TI  - Meetings of Societies.

PMID- 29646027
TI  - Medical News.

PMID- 29646028
TI  - On the Radical Treatment of Hernia with the Aid of Catgut and Listerian
      Antiseptics.

PMID- 29646029
TI  - Practical Observations on Some of the More Common Diseases of Early Life.

PMID- 29646030
TI  - Monthly Retrospect of Obstetrics and Gynaecology.

PMID- 29646032
TI  - A Rare Case of Bullet in the Brain for Sixty-Five Years.

PMID- 29646031
TI  - Occasional Periscope of Dermatology.

PMID- 29646033
TI  - Periscope of Otology.

PMID- 29646035
TI  - On Tinea Imbricata, or Tokelau Ringworm.

PMID- 29646034
TI  - Medical News.

PMID- 29646036
TI  - A Case of Arrested Development of the Cerebellum and the Bones of the Skull in a
      Child.

PMID- 29646037
TI  - Scarlet Fever in the Puerperium.

PMID- 29646038
TI  - Meetings of Societies.

PMID- 29646039
TI  - On Medical Education and Reform: Address to the Medical Graduates of the
      University of Edinburgh, 2d August 1880.

PMID- 29646040
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29646041
TI  - Upon the Causes, Prevention, and Treatment of Afterpains.

PMID- 29646042
TI  - Comparison between the Scoliotic and Obliquely Contracted (Naegele) Pelves.

PMID- 29646043
TI  - Overpopulation and Its Proposed Treatment by Lessening the Birth-Rate.

PMID- 29646044
TI  - On Axis-Traction Forceps.

PMID- 29646045
TI  - Report of and Observations upon Two Cases of Puerperal Septicaemia.

PMID- 29646046
TI  - Monthly Retrospect of Obstetrics and Gynaecology.

PMID- 29646047
TI  - Periscope of Otology.

PMID- 29646048
TI  - On the Riviera, Madeira, the Canary Islands, and Davos, with Reference to Their
      Climate for Consumptive Invalids.

PMID- 29646049
TI  - A Bill to Amend the Law Relating to the Unlawful Administering of Poison.

PMID- 29646050
TI  - Royal College of Surgeons-Conversazione.

PMID- 29646051
TI  - Electricity as a Means of Light in Surgical Operations, Etc.

PMID- 29646052
TI  - Army Medical Department.

PMID- 29646053
TI  - Scottish Universities Commission.

PMID- 29646054
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29646055
TI  - Medicine.

PMID- 29646056
TI  - Midwifery.

PMID- 29646057
TI  - Royal Medical Society-Conversazione.

PMID- 29646058
TI  - On the Prevalence of Heat Apoplexy among Soldiers during the Hot-Weather Campaign
      in 1858.

PMID- 29646059
TI  - Clinical Notes.

PMID- 29646061
TI  - University of Edinburgh.

PMID- 29646060
TI  - The Indian Medical Service and the New Warrant.

PMID- 29646062
TI  - Some Remarks on a Certain Unusual Form of Arterial Obstruction.

PMID- 29646063
TI  - Varieties.

PMID- 29646064
TI  - Surgery.

PMID- 29646065
TI  - Museum of Morbid Anatomy at Fort Pitt.

PMID- 29646067
TI  - Report of General Board of Lunacy for Scotland.

PMID- 29646066
TI  - Case of Rupture of the Urinary Bladder.

PMID- 29646068
TI  - Army Medical School.

PMID- 29646069
TI  - Penalties Attached to the Registration of Deaths.

PMID- 29646070
TI  - Account of the Aurengzebie, or Delhi Sore.

PMID- 29646071
TI  - On Tracheotomy in Croup.

PMID- 29646072
TI  - On Retroflexion of the Unimpregnated Uterus; with Cases Illustrative of Its
      Causes and of a New Mode of Treatment.

PMID- 29646073
TI  - Sick Children's Hospital.

PMID- 29646074
TI  - Physiology.

PMID- 29646075
TI  - Small-Pox in Scotland, as It Is, Was, and Ought to Be; with Hints for Its
      Mitigation by Legislative Enactment.

PMID- 29646077
TI  - The London and Dublin Colleges of Surgeons.

PMID- 29646076
TI  - On the True Relation between Synovitis and Ulceration of Articular Cartilage.

PMID- 29646078
TI  - Midwifery.

PMID- 29646079
TI  - Surgery.

PMID- 29646080
TI  - Remarks on the Musculus Kerato-Cricoideus, a Muscle of the Larynx (Merkel's
      Muscle).

PMID- 29646082
TI  - Varieties.

PMID- 29646081
TI  - Cases of Tracheotomy in Croup, with Clinical Remarks.

PMID- 29646083
TI  - On Pericarditis.

PMID- 29646084
TI  - Circular Accompanying General Order as to Qualifications of Medical Officers.

PMID- 29646085
TI  - Scottish Branch of General Council of Medical Education and Registration.

PMID- 29646086
TI  - Notes of an Epidemic of Diphtheria.

PMID- 29646087
TI  - Conversazione at the Royal College of Surgeons.

PMID- 29646088
TI  - Chair of Surgery in Glasgow-Extraordinary Proceeding.

PMID- 29646089
TI  - Medicine.

PMID- 29646090
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29646091
TI  - Contributions to the Natural History of General Paralysis.

PMID- 29646092
TI  - Position of Medical Graduates under the New Scotch Reform Bill.

PMID- 29646093
TI  - Case of Abdominal Abscess, with Extensive Mortification, and Recovery.

PMID- 29646095
TI  - Surgery.

PMID- 29646094
TI  - Royal College of Surgeons-Conversazione.

PMID- 29646096
TI  - The War Office, Contagion and Fumigation.

PMID- 29646097
TI  - Return of Births, Deaths, and Marriages in Scotland for the Year 1859.

PMID- 29646098
TI  - Scottish Registered Medical Practitioners' Association.

PMID- 29646099
TI  - Medicine.

PMID- 29646100
TI  - Observations on Some of the Daily Changes of the Urine.

PMID- 29646101
TI  - On the Rational Treatment of Delirium Tremens.

PMID- 29646102
TI  - Hygiene.

PMID- 29646103
TI  - Clinical Notes.

PMID- 29646104
TI  - Toxicology.

PMID- 29646105
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29646106
TI  - Varieties.

PMID- 29646108
TI  - Surgery.

PMID- 29646107
TI  - Hora Harveiana: An Address Delivered at the Annual Meeting of the Harveian
      Society, Edinburgh, April 13, 1860.

PMID- 29646109
TI  - Notes on an Epidemic of Diphtheria.

PMID- 29646110
TI  - Quarterly Return of Births, Deaths, and Marriages.

PMID- 29646111
TI  - Case of Cancer of the Bladder.

PMID- 29646112
TI  - Installation of Lord Brougham as Chancellor of Edinburgh University.

PMID- 29646113
TI  - Notes on the State of Lithotomy, past and Present. From a Lecture.

PMID- 29646114
TI  - Treatment of Onyxis with Nitrate of Silver.

PMID- 29646115
TI  - Toxicology.

PMID- 29646117
TI  - Medicine.

PMID- 29646116
TI  - Remarks on Dr Farr's Proposed New Statistical Classification of Diseases for
      Statistical Returns.

PMID- 29646118
TI  - Errata.
AB  - [This corrects the article on p. 1037 in vol. 5.].

PMID- 29646119
TI  - On Opium as a Remedy in Poisoning by Datura.

PMID- 29646120
TI  - Errata.
AB  - [This corrects the article on p. 843 in vol. 5.].

PMID- 29646121
TI  - Varieties.

PMID- 29646122
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29646123
TI  - Clinical Notes.

PMID- 29646125
TI  - Medicine.

PMID- 29646124
TI  - Historical Sketch of the Royal College of Surgeons of Edinburgh; Being an Address
      Delivered in the Hall of the College in Nicolson Street, at a Conversazione on
      19th January 1860: With Notes and Documents.

PMID- 29646126
TI  - Qrarterly Return of Births, Deaths, and Marriages.

PMID- 29646127
TI  - On Calculus and Cholera in India.

PMID- 29646128
TI  - Observations on Some of the Daily Changes of the Urine.

PMID- 29646129
TI  - Opening in Drummond Street, Edinburgh, of a Dispensary for Diseases of the Teeth.

PMID- 29646131
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29646130
TI  - Quarterly Report of Cases Occurring at the Edinburgh Eye Infirmary, 140, George
      Street.

PMID- 29646133
TI  - Surgery.

PMID- 29646132
TI  - Address to the Medical Profession.

PMID- 29646134
TI  - Case of Hydatid Tumour and Abscess of the Liver.

PMID- 29646135
TI  - Varieties.

PMID- 29646136
TI  - Trial of Two Medical Men for Practising Syphilitic Inoculation at Lyons.

PMID- 29646138
TI  - The Late Director-General of the Army Medical Department.

PMID- 29646137
TI  - Case of Pyoemia with Typhus Fever.

PMID- 29646139
TI  - On the Uterine Leucorrhoea of Old Women.

PMID- 29646141
TI  - Hygiene.

PMID- 29646140
TI  - Physiology.

PMID- 29646142
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29646144
TI  - Edinburgh Obstetrical Society.

PMID- 29646143
TI  - Cases Communicated.

PMID- 29646145
TI  - On Tracheotomy in Croup.

PMID- 29646146
TI  - Royal Medical Society, Edinburgh.

PMID- 29646147
TI  - University of Edinburgh.

PMID- 29646148
TI  - Report of the Missionary Hospital at Kum-Lee-Fow, in the Western Suburbs of
      Canton, for the Year 1858-9.

PMID- 29646149
TI  - Case of Tumour of the Brain.

PMID- 29646150
TI  - The Principalship of the United College, St Andrews.

PMID- 29646151
TI  - Acupressure-A New Method of Arresting Surgical Hoemorrhage.

PMID- 29646152
TI  - Account of the Illness and Death of Dr William Pulteney Alison, Emeritus
      Professor of the Practice of Physic in the University of Edinburgh.

PMID- 29646153
TI  - Medicine.

PMID- 29646154
TI  - Public Vaccination.

PMID- 29646155
TI  - Varieties.

PMID- 29646156
TI  - Poisoning by Carbonic Acid Gas, with Recovery.

PMID- 29646158
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29646157
TI  - Case of Extensive Adhesion of the Inferior Margin of the Soft Palate to the
      Posterior Wall of the Fauces, with a Description of the Parts Seen on Dissection.

PMID- 29646159
TI  - Surgery.

PMID- 29646160
TI  - Case of Caesarean Section, with Successful Results to Both Mother and Child.

PMID- 29646161
TI  - An Account of Tubercular Leprosy in the Island of Madagascar.

PMID- 29646163
TI  - Proceedings of the Edinburgh Obstetrical Society.

PMID- 29646162
TI  - Surgical Cases.

PMID- 29646164
TI  - Remarks on Syphilis and Its Treatment.

PMID- 29646165
TI  - Report of the Trial of George Bryce for Murder.

PMID- 29646167
TI  - Case of Death Resulting from the Practice of Arsenic-Eating.

PMID- 29646166
TI  - Observations on Shoulder Presentations of the Foetus.

PMID- 29646168
TI  - Proceedings of the Edinburgh Obstetrical Society.

PMID- 29646169
TI  - Practice of Medicine.

PMID- 29646170
TI  - The Physiological Actions of Dajaksch, an Arrow Poison, Used in Borneo.

PMID- 29646171
TI  - Royal Medical and Chirurgical Society.

PMID- 29646172
TI  - Case of Rupture of the Uterus, in Which Gastrotomy Was Successfully Performed.

PMID- 29646173
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29646175
TI  - Further Observations on the Waxy or Amyloid Form of Bright's Disease.

PMID- 29646174
TI  - Report of the Trial of Thomas Arnot for Murder.

PMID- 29646176
TI  - Note on a Case of Poisoning by the Calabar Bean.

PMID- 29646178
TI  - Medical Practitioners in Melbourne.

PMID- 29646177
TI  - Cases of Delirium Tremens Treated with Large Doses of the Tincture of Digitalis.

PMID- 29646179
TI  - Twelve Cases of Ovariotomy.

PMID- 29646180
TI  - Medical Jurisprudence.

PMID- 29646181
TI  - On the Treatment of Albuminuria in Children.

PMID- 29646182
TI  - On Some Customs of the People of Old Calabar Relative to Pregnancy and
      Parturition.

PMID- 29646183
TI  - Fourteen Cases of Ovariotomy.

PMID- 29646184
TI  - Contagious Diseases Bill.

PMID- 29646185
TI  - Midwifery.

PMID- 29646186
TI  - Surgery.

PMID- 29646187
TI  - Cosmic Sensibility.

PMID- 29646189
TI  - A Few Words Concerning Bantingism.

PMID- 29646188
TI  - The Medical Warrant for India.

PMID- 29646190
TI  - Extensive Poisoning by the Calabar Bean.

PMID- 29646192
TI  - Memorial of the Royal College of Surgeons of Edinburgh.

PMID- 29646191
TI  - Petition of the President and Fellows of the Faculty of Physicians and Surgeons
      of Glasgow.

PMID- 29646193
TI  - On the Wire Compress as a Substitute for the Ligature.

PMID- 29646194
TI  - Proceedings of the Edinburgh Obstetrical Society.

PMID- 29646195
TI  - Notes of a Case of Alopecia Areata Treated by Carbolic Acid.

PMID- 29646196
TI  - Why Animals to Be Eaten Must Be Killed.

PMID- 29646197
TI  - Graduation in Medicine at the University of Edinburgh.

PMID- 29646199
TI  - Homoeopathy and Mathematics.

PMID- 29646198
TI  - Army Medical Service.-Assistant Surgeons.

PMID- 29646200
TI  - On the Results of Recent Improvements in Operative Midwifery in Diminishing the
      Number of Cases Requiring Embryotomy.

PMID- 29646202
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29646201
TI  - On the Arsenic-Eaters of Styria.

PMID- 29646203
TI  - Army Medical School.

PMID- 29646204
TI  - Introductory Lecture at the Medical School, Surgeons' Hall.

PMID- 29646206
TI  - The Edinburgh School of Surgery: An Introductory Lecture.

PMID- 29646205
TI  - Remarks on Syphilization as a Cure for Constitutional Syphilis.

PMID- 29646207
TI  - Erratum.
AB  - [This corrects the article on p. 431 in vol. 10.].

PMID- 29646208
TI  - The Faculty of Medicine of Paris.

PMID- 29646209
TI  - Midwifery.

PMID- 29646210
TI  - Case of Ovariotomy.

PMID- 29646211
TI  - Indian Medical Department.

PMID- 29646212
TI  - The Morison Lectureship on Mental Diseases.

PMID- 29646213
TI  - Army Medical Department.

PMID- 29646214
TI  - Report of Investigation in the Case of J. S. Love, an Insane Prisoner.

PMID- 29646215
TI  - The Compulsory Vaccination Act.

PMID- 29646216
TI  - On the Weight and Length of the Newly-Born Child in Relation to the Mother's Age.

PMID- 29646217
TI  - Medical School, Surgeons' Hall.

PMID- 29646219
TI  - Medical Jurisprudence.

PMID- 29646218
TI  - On the Advantages of a More Extended Use of Version in Cases of Disproportion.

PMID- 29646220
TI  - University of Edinburgh-Number of Students.

PMID- 29646221
TI  - Proceedings of the Edinburgh Obstetrical Society.

PMID- 29646222
TI  - On an Alleged Fallacy in Marsh's Process for the Detection of Arsenic.

PMID- 29646223
TI  - Royal College of Surgeons of Edinburgh.

PMID- 29646224
TI  - Great Mortality in the Washington Hospitals.

PMID- 29646225
TI  - Case of Popliteal Aneurism a Second Time Treated Successfully by Compression.

PMID- 29646227
TI  - On the Painless Extinction of Life in Animals Designed for Human Food.

PMID- 29646226
TI  - Amputation at the Hip-Joint.

PMID- 29646228
TI  - Remarks on the Compulsory Vaccination Act for Scotland.

PMID- 29646230
TI  - Faculty of Medicine, Paris.

PMID- 29646229
TI  - The Medical Service of the Army.

PMID- 29646231
TI  - The London Medical Schools.

PMID- 29646233
TI  - Royal College of Surgeons of England.

PMID- 29646232
TI  - Statistical Account of Cases Admitted into the Clinique of M. Velpeau at La
      Charite, during the Year 1863-64.

PMID- 29646234
TI  - M. Trousseau and the Chair of Therapeutics.

PMID- 29646235
TI  - On the Employment of Chloroform in Dental Surgery.

PMID- 29646236
TI  - Some Observations on Scrofula on the North-East Coast of Scotland.

PMID- 29646237
TI  - Yellow Fever at Bermuda.

PMID- 29646239
TI  - Excision of Superior Maxillary Bone.

PMID- 29646238
TI  - On Supporting the Perinaeum as a Preventive of Laceration at Childbirth.

PMID- 29646240
TI  - Materia Medica and Therapeutics.

PMID- 29646241
TI  - A French Account of English Hospital Physicians.

PMID- 29646242
TI  - A Few Words on the Evidence against the Internal Use of Mercury in Syphilis and
      Other Diseases.

PMID- 29646243
TI  - Faculty of Physicians and Surgeons, Glasgow: Abstract of Regulations for the
      Election and Admission of Fellows.

PMID- 29646244
TI  - Two Cases of Ague, with a Few Remarks on the Same.

PMID- 29646245
TI  - Practice of Medicine.

PMID- 29646246
TI  - Army Medical Department.

PMID- 29646247
TI  - Loss of the Second Phalanx of the Left Thumb with the Tendon of the Flexor Longis
      Pollicis.

PMID- 29646248
TI  - List of Hospitals, Dispensaries, Etc., in Connexion with the Medical Schools of
      Scotland.

PMID- 29646249
TI  - Election of Professor to the Chair of Surgery in the Edinburgh University.

PMID- 29646250
TI  - Information Regarding the Requirements in Preliminary and Professional Education
      of the Various Licensing Bodies.

PMID- 29646251
TI  - Dr. E. Smith on Dietetics.

PMID- 29646252
TI  - Graduation Address to the Gentlemen Who Obtained the Degree of M.D. in the
      University of Edinburgh, 1st August 1864.

PMID- 29646253
TI  - On Insufflation as a Remedy in Intussusception.

PMID- 29646255
TI  - Navy Medical Department.

PMID- 29646254
TI  - Two Cases of Strangulated Inguinal Hernia.

PMID- 29646256
TI  - Royal College of Surgeons of Edinburgh: Abstract of Regulations for the
      Fellowship.

PMID- 29646257
TI  - Surgery.

PMID- 29646258
TI  - Case of Degeneration and Atrophy of the Cerebrum, Causing Unilateral Epilepsy.

PMID- 29646259
TI  - Royal College of Physicians of Edinburgh: Regulations Regarding the Fellowship
      and Membership of the College.

PMID- 29646260
TI  - Faculty of Physicians and Surgeons, Glasgow: Abstract of Regulations for the
      Election and Admission of Fellows.

PMID- 29646261
TI  - Army Medical Department.

PMID- 29646263
TI  - Royal College of Physicians of Edinburgh: Regulations Regarding the Fellowship
      and Membership of the College.

PMID- 29646262
TI  - Clinical Notes from the Dumfries Royal Infirmary.

PMID- 29646264
TI  - Commissions in the Indian Medical Service.

PMID- 29646265
TI  - British Medical Association.

PMID- 29646266
TI  - Information Regarding Medical Education and Examinations.

PMID- 29646267
TI  - Royal College of Surgeons of Edinburgh: Abstract of Regulations for the
      Fellowship.

PMID- 29646268
TI  - Notes on the Prison Dietaries in Scotland.

PMID- 29646269
TI  - List of Hospitals, Dispensaries, Etc., in Connexion with the Medical Schools of
      Scotland.

PMID- 29646270
TI  - The Address in Medicine.

PMID- 29646272
TI  - Navy Medical Department.

PMID- 29646271
TI  - Historical Sketch of the Edinburgh Anatomical School.

PMID- 29646273
TI  - Army Medical School.

PMID- 29646274
TI  - Cases of Thoracic Aneurism.

PMID- 29646275
TI  - Report of Clinical Cases Treated in the Surgical Wards of the Royal Infirmary,
      under the Care of Professor Spence, from October 1864 to October 1865.

PMID- 29646276
TI  - Practice of Medicine.

PMID- 29646277
TI  - General Council of Medical Education and Registration.

PMID- 29646278
TI  - Case of Addison's Disease.

PMID- 29646279
TI  - Notes on the Prison Dietaries in Scotland.

PMID- 29646280
TI  - On the Mode of Action of Strychnia.

PMID- 29646281
TI  - Case of Removal of a Fibroid Tumour of the Uterus, Weighing 29 lbs.

PMID- 29646282
TI  - Sir Thomas Watson, M.D., Bart.

PMID- 29646283
TI  - Meetings of Societies.

PMID- 29646284
TI  - On the Treatment of Pneumonia.

PMID- 29646285
TI  - The Two Services.

PMID- 29646286
TI  - Practice of Medicine.

PMID- 29646287
TI  - The Cholera at Liverpool.

PMID- 29646288
TI  - Medical Reform.

PMID- 29646289
TI  - On the Milk Cure.

PMID- 29646290
TI  - Army Medical Service.

PMID- 29646292
TI  - Cholera in the London Hospitals.

PMID- 29646291
TI  - On Diphtheria.

PMID- 29646293
TI  - Case of Cancer of the Lumbar Glands Simulating Abdominal Aneurism.

PMID- 29646294
TI  - Two Cases of Aphasia and Right Hemiplegia, with Dissections.

PMID- 29646295
TI  - Case of Air Found in the Chambers of the Heart.

PMID- 29646296
TI  - Visitation of Examinations in Scotland.

PMID- 29646297
TI  - Honour to Medicine.

PMID- 29646298
TI  - Faculty of Medicine of Paris.

PMID- 29646300
TI  - Greenock Medical Society.

PMID- 29646299
TI  - Notice of Some of the Therapeutic Effects of the Bromide of Potassium.

PMID- 29646301
TI  - Cases of Ovariotomy.

PMID- 29646303
TI  - Medical School, Surgeons' Hall.

PMID- 29646302
TI  - Medical Students in London.

PMID- 29646304
TI  - University of Edinburgh-Number of Students.

PMID- 29646305
TI  - On the Pathology of Cholera Collapse.

PMID- 29646306
TI  - Case of Excision of One Lateral Half of the Tongue.

PMID- 29646307
TI  - Opening of the Faculty of Medicine, Paris.

PMID- 29646308
TI  - Historical Sketch of the Edinburgh Anatomical School.

PMID- 29646309
TI  - On the Management of the Second Stage of Natural Labour.

PMID- 29646310
TI  - Aphasia and Death Resulting from Softening in Left Anterior Cerebral Lobe and
      Cerebellum, Due to Atheromatous Degeneration and Embolism of the Cerebral
      Arteries.

PMID- 29646312
TI  - Pathology.

PMID- 29646311
TI  - Report of Clinical Cases Treated in the Surgical Wards of the Royal Infirmary,
      under the Care of Professor Spence, from October 1864 to October 1865.

PMID- 29646313
TI  - Midwifery.

PMID- 29646315
TI  - Practice of Medicine.

PMID- 29646314
TI  - History of an Epidemic of Rotheln, with Observations on Its Pathology.

PMID- 29646316
TI  - The Modern Treatment of Pneumonia in Young Children, with Some Observations on
      the Initial Auscultatory Sign of the Disease.

PMID- 29646318
TI  - International Medical Congress at Paris.

PMID- 29646317
TI  - Historical Sketch of the Edinburgh Anatomical School.

PMID- 29646319
TI  - Errata.
AB  - [This corrects the article on p. 360 in vol. 12.].

PMID- 29646320
TI  - Disinfection of Cholera.

PMID- 29646321
TI  - Elephantiasis of the Scrotum.

PMID- 29646322
TI  - Royal College of Surgeons.

PMID- 29646323
TI  - Some Remarks on Cholera, with Reminiscences of the Epidemic of 1832.

PMID- 29646324
TI  - The Cholera Mist Again.

PMID- 29646325
TI  - Practice of Medicine.

PMID- 29646326
TI  - Graduation Address to the Gentlemen Who Obtained Their Medical Degree in the
      University of Edinburgh, 1st August 1866.

PMID- 29646327
TI  - The Faculty of Physicians and Surgeons of Glasgow.

PMID- 29646328
TI  - Observations on the Physiology of the Larynx.

PMID- 29646330
TI  - The Cholera in Paris.

PMID- 29646329
TI  - On the Age of Nubility.

PMID- 29646331
TI  - Commissions in the British Medical Service.

PMID- 29646332
TI  - Meetings of Societies.

PMID- 29646334
TI  - Graduation in Medicine at the University of Edinburgh.

PMID- 29646333
TI  - Edinburgh Medical Students' Christian Association.

PMID- 29646335
TI  - Suggestions Made for Preparation for the Advent of Asiatic Cholera: By a
      Committee of the Royal College of Physicians of Edinburgh, at the Request of the
      Chairman of the Board of Supervision for the Relief of the Poor in Scotland,
      August 1866.

PMID- 29646337
TI  - Regulations as to the Pay and Position of Naval Medical Officers.

PMID- 29646336
TI  - On Dislocation at the Shoulder-Joint.

PMID- 29646338
TI  - Remarks on a Case of Spurious Menstruation during Pregnancy.

PMID- 29646339
TI  - Varieties.

PMID- 29646340
TI  - Midwifery.

PMID- 29646341
TI  - Case of Imperforate Anus. Proposed Modification in Operative Interference.

PMID- 29646342
TI  - Lunacy Bill for Scotland.

PMID- 29646343
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29646344
TI  - A Case of Successful Deligation of the Subclavian Artery, for the Cure of a Large
      Axillary Aneurism.

PMID- 29646345
TI  - Alcohol, Its Place and Power.

PMID- 29646346
TI  - Remarks on That Form of Moral Insanity Called Dipsomania, and the Legality of Its
      Treatment by Isolation.

PMID- 29646348
TI  - Obstetrical Society of Edinburgh.

PMID- 29646347
TI  - Starch as a Constituent of the Animal Organism.

PMID- 29646349
TI  - Half-Yearly Report of Cases Occurring at the Edinburgh Eye Infirmary.

PMID- 29646351
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29646350
TI  - Cases in Surgical Practice.

PMID- 29646352
TI  - Case of Aneurism of the Aorta, with Laryngeal Spasm, in Which Tracheotomy Was
      Performed, with Remarks.

PMID- 29646353
TI  - Varieties.

PMID- 29646355
TI  - Medical Jurisprudence.

PMID- 29646354
TI  - Clinical Notes.

PMID- 29646356
TI  - Case of Acute Meningitis Treated by Early Blood-Letting.

PMID- 29646357
TI  - On the Changes Which Have Taken Place in the Constitution of Fevers and
      Inflammations in Edinburgh during the Last Forty Years.

PMID- 29646358
TI  - Case of a Ruptured External Iliac Aneurism, Treated by Ligature of the Common
      Iliac Artery.

PMID- 29646359
TI  - Therapeutical Record.

PMID- 29646360
TI  - The Action of Cod-Liver Oil, and the Substitution of Ordinary Fats in Food.

PMID- 29646361
TI  - Some Further Remarks on the Internal Surface of the Uterus, and on Its Relations
      with the Placenta.

PMID- 29646362
TI  - Midwifery.

PMID- 29646363
TI  - Case of Aortic Aneurism Pressing on the Left Bronchus, and Proving Fatal by
      Hemorrhage.

PMID- 29646364
TI  - Medicine.

PMID- 29646365
TI  - Arsenic: Its Physiological and Therapeutical Effects; with Reflections on the
      Relations of Certain Diseases, Their Common Origin, and Treatment.

PMID- 29646366
TI  - Varieties.

PMID- 29646367
TI  - Notes of a Case of Ileus, Caused by a Large Gall-Stone Impacted in the Ileum;
      Death from Rupture of the Heart.

PMID- 29646368
TI  - On Adherent Pericardium; Its Diagnosis and Its Results.

PMID- 29646369
TI  - Royal College of Surgeons-Conversazione.

PMID- 29646370
TI  - On the Communication of the Infection of Fever by Ingesta.

PMID- 29646372
TI  - Medical Jurisprudence.

PMID- 29646371
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29646374
TI  - Royal College of Surgeons-Conversazione.

PMID- 29646373
TI  - Dietary at a Homoeopathic Hospital.

PMID- 29646375
TI  - Toxicology.

PMID- 29646377
TI  - Cases in Surgical Practice.

PMID- 29646376
TI  - Cases of Tracheotomy in Croup, and for the Removal of Foreign Bodies.

PMID- 29646378
TI  - On the Medicinal Action of Lupuline.

PMID- 29646380
TI  - Therapeutical Record.

PMID- 29646379
TI  - Case of Chylous or Fatty Urine.

PMID- 29646382
TI  - Varieties.

PMID- 29646381
TI  - Midwifery.

PMID- 29646383
TI  - British Medical Association.

PMID- 29646384
TI  - On the Nature and Mode of Formation of the So-Called Hyaline Bodies Found in
      Pathological Effusions.

PMID- 29646385
TI  - Notes on the History of the Mucous Membrane of the Body of the Uterus. William
      and John Hunter.

PMID- 29646386
TI  - The Condition of the Lung Not Invariably to Be Depended On, as a Proof That the
      Infant Has Been Born Alive.

PMID- 29646387
TI  - Road Reform-Claims of Surgeons.

PMID- 29646388
TI  - Remarks on Two Cases of Poisoning by Opium in Young Children.

PMID- 29646389
TI  - Clinical Lecture on Pneumonia, Delivered in the Glasgow Royal Infirmary on the
      11th January 1858.

PMID- 29646390
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29646391
TI  - Royal Medical Society-Conversazione.

PMID- 29646392
TI  - Varieties.

PMID- 29646393
TI  - Syphilization; Its Mode of Performance and Its Results.

PMID- 29646395
TI  - Facts on the Question of the Average Duration of Pregnancy.

PMID- 29646394
TI  - On What Is the Theory of a Change of Type in Disease Based?

PMID- 29646396
TI  - Hygiene.

PMID- 29646398
TI  - The Spread of Cholera by Personal Communication, as Seen in the Crimean Campaign.

PMID- 29646397
TI  - On a Case of Spontaneous Gangrene from Arteritis, and on the Causes of
      Coagulation of the Blood in Diseases of the Blood-Vessels.

PMID- 29646399
TI  - Half-Yearly Medical Report of Fife County Prison, Ending December 31, 1857.

PMID- 29646400
TI  - Hereditary Predisposition to Dipsomania.

PMID- 29646401
TI  - Removal of a Cancerous Cervix Uteri by Means of the Ecraseur. With Remarks.

PMID- 29646402
TI  - Royal College of Surgeons-Conversazione.

PMID- 29646403
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29646404
TI  - Some Remarks on the Proper Design of the Semilunar Lines of Douglas. With Three
      Illustrations.

PMID- 29646405
TI  - Medicine.

PMID- 29646407
TI  - Medical Jurisprudence.

PMID- 29646406
TI  - Tetanus Treated with Extract of Indian Hemp: Recovery.

PMID- 29646408
TI  - Toxicology.

PMID- 29646409
TI  - Case of Infantile Convulsions; Successfully Treated by Carbonate of Iron, after
      Failure by Other Means.

PMID- 29646410
TI  - On the Influence of the Woollen Manufactures on Health.

PMID- 29646411
TI  - On the Results of Adherent Pericardium.

PMID- 29646412
TI  - Remarks on the Pathology of Syphilis and Gonorrhoea.

PMID- 29646413
TI  - The Reaction of the Urine in Disease and in Treatment.

PMID- 29646414
TI  - Natural Chemical Stimulators.

PMID- 29646415
TI  - Clinical Meeting.

PMID- 29646416
TI  - Intrapleural Division of Adhesions in the Pneumothorax Treatment of Pulmonary
      Tuberculosis. (Internal Pneumolysis).

PMID- 29646417
TI  - The Effect of Reticulo-Endothelial Blockade on Natural Antibodies and Natural
      Immunity Reactions.

PMID- 29646418
TI  - Debatable Tumours in Human and Animal Pathology-V. Giant-Cell Tumour of Bone.

PMID- 29646419
TI  - Abdominal Symptoms in Cardiac Disease.

PMID- 29646421
TI  - Recovery and Rehabilitation.

PMID- 29646420
TI  - The Streptococcal Diseases.

PMID- 29646422
TI  - Haemorrhoids and Their Treatment.

PMID- 29646423
TI  - Clinical Meeting.

PMID- 29646424
TI  - Zinc Protamine Insulin.

PMID- 29646425
TI  - OEstrogenic and Androgenic Substances in Pregnancy.

PMID- 29646426
TI  - Sprained Ankle.

PMID- 29646427
TI  - Some Aspects of Thyrotoxicosis and the Results of Treatment.

PMID- 29646428
TI  - Passages of Medical History-Edinburgh Medicine, 1828-1860.

PMID- 29646429
TI  - Notes.

PMID- 29646430
TI  - The Therapeutic Use of Barbiturates.

PMID- 29646431
TI  - The Incidence of Favus in Scotland.

PMID- 29646432
TI  - Bronchiectasis-A Fatal Disease.

PMID- 29646434
TI  - Meetings of Societies.

PMID- 29646433
TI  - Debatable Tumours in Human and Animal Pathology-VI. Meningioma.

PMID- 29646435
TI  - On the Physiological Actions of the Ordeal Bean of Calabar, and on Its Antagonism
      to Tetanus and Strychnia-Poisoning.

PMID- 29646436
TI  - Conversazione at the Royal College of Surgeons.

PMID- 29646437
TI  - On Ventilation and Cubic Space.

PMID- 29646438
TI  - Doctor's Jubilee of Professor Romberg.

PMID- 29646439
TI  - On the Reduction of Dislocations of the Hip-Joint by Manipulation.

PMID- 29646441
TI  - Surgery.

PMID- 29646440
TI  - French Lunacy Statistics.

PMID- 29646442
TI  - Mortality of Diseases in Sweden.

PMID- 29646443
TI  - Abstract of the Medical Report, for the Year Ending 31st December 1866, of the
      General Prison for Scotland.

PMID- 29646444
TI  - Medicine.

PMID- 29646446
TI  - Appointment to the Chair of Anatomy in the University of Edinburgh.

PMID- 29646445
TI  - On the Production of Inverted Uterus.

PMID- 29646447
TI  - Encephalocele Successfully Removed.

PMID- 29646448
TI  - Commissions in the Indian Medical Service.

PMID- 29646449
TI  - Appointments.

PMID- 29646450
TI  - Meetings of Societies.

PMID- 29646451
TI  - Note on Preparation Jars.

PMID- 29646452
TI  - Case of Amputation at Knee-Joint, by Dr Johnston, Montrose.

PMID- 29646453
TI  - Influence of Marriage on the Death-Rates of Men and Women in Scotland.

PMID- 29646455
TI  - Naval Medical Department.

PMID- 29646454
TI  - Midwifery Statistics of Sweden.

PMID- 29646456
TI  - The French International Medical Congress.

PMID- 29646457
TI  - On the Pathology of Tubercular Meningitis.

PMID- 29646458
TI  - Goodsir Fellowship in Anatomy and Physiology.

PMID- 29646459
TI  - The Permanganates in Diphtheria.

PMID- 29646460
TI  - Cases of Excision of the Knee-Joint, Illustrative of a New Method of after
      Treatment.

PMID- 29646461
TI  - Medicine.

PMID- 29646462
TI  - Royal Infirmary.

PMID- 29646463
TI  - Election of Professor of Botany in University of Dublin.

PMID- 29646465
TI  - Inoculation Introduced into France by Voltaire.

PMID- 29646464
TI  - Diphtheria.

PMID- 29646466
TI  - Short History of the Outbreak of Cholera Which Recently Prevailed at Slateford,
      near Edinburgh.

PMID- 29646468
TI  - Curious Case of Hermaphroditism in 1654.

PMID- 29646467
TI  - Case of Traumatic Tetanus Successfully Treated by the Direct Application of
      Infusion of Tobacco.

PMID- 29646469
TI  - Case of Aphasia with Right Hemiplegia; Death; Autopsy; Lesion of a Large Portion
      of the Left Cerebral Hemisphere, Including the External or Inferior Left Frontal
      Convolution; Embolism of Branches of the Left Middle Cerebral Artery.

PMID- 29646471
TI  - Surgery.

PMID- 29646470
TI  - Haemorrhage from Fibrous Tumour of the Uterus: Its Nature, Source, and Surgical
      Treatment.

PMID- 29646472
TI  - Excision of One Lateral Half of the Tongue.

PMID- 29646473
TI  - Meetings of Societies.

PMID- 29646474
TI  - On a Mode of Treatment for Ununited Fracture.

PMID- 29646475
TI  - On the Neglect of the Study of Skin Diseases in England.

PMID- 29646476
TI  - Conversazione at the Royal College of Surgeons of Edinburgh.

PMID- 29646477
TI  - Meetings of Societies.

PMID- 29646478
TI  - Colles's Fracture.

PMID- 29646479
TI  - French International Medical Congress.

PMID- 29646480
TI  - Goodsir Fellowship in Anatomy and Physiology.

PMID- 29646481
TI  - Case of Suppression of Urine, Fatal on the Thirteenth Day.

PMID- 29646483
TI  - Return of Professor Laycock.

PMID- 29646482
TI  - The Life, Character, and Writings of William Hey of Leeds: A Discourse Delivered
      at the Annual Meeting of the Harveian Society, Edinburgh, April 12, 1867.

PMID- 29646484
TI  - Surgery.

PMID- 29646485
TI  - Materia Medica.

PMID- 29646486
TI  - On Chloroform in London.

PMID- 29646488
TI  - Professor Syme's Treatment of Aneurism.

PMID- 29646487
TI  - Cases Illustrative of the Insanity of Pregnancy, Puerperal Mania, and Insanity of
      Lactation.

PMID- 29646489
TI  - Commissions in the British Medical Service.

PMID- 29646490
TI  - On the Legal Relations of Insanity: The Civil Incapacity and Criminal
      Responsibility of the Insane.

PMID- 29646491
TI  - Remarkable Case of Cervical Abscess in an Infant, Caused by the Swallowing of a
      Piece of Glass.

PMID- 29646492
TI  - Medicine.

PMID- 29646494
TI  - Surgery.

PMID- 29646493
TI  - Introductory Address Delivered at Surgeons' Hall, Edinburgh, at the Opening of
      the Medical Session, October 1866.

PMID- 29646495
TI  - Naval Medical Department.

PMID- 29646496
TI  - On the Comparative Value of the Long Forceps and Turning in Cases of Contracted
      Pelvic Brim: With Cases.

PMID- 29646497
TI  - Meetings of Societies.

PMID- 29646498
TI  - On the Use of Chlorine in the Treatment of Asiatic Cholera and Choleraic
      Diarrhoea.

PMID- 29646499
TI  - Dr Charles Bell on the Permanganates in Diphtheria.

PMID- 29646500
TI  - Appointment to the Lecturership on Materia Medica at the Medical School,
      Surgeons' Hall, Edinburgh.

PMID- 29646502
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29646501
TI  - Meetings of Societies.

PMID- 29646504
TI  - Pathology.

PMID- 29646503
TI  - Royal College of Physicians of Edinburgh.

PMID- 29646505
TI  - On Excision of the Knee-Joint, and the Employment of a New Apparatus in the After
      Treatment.

PMID- 29646506
TI  - Uterine Surgery.

PMID- 29646507
TI  - Therapeutics.

PMID- 29646508
TI  - Haemorrhage from Fibrous Tumour of the Uterus: Its Nature, Source, and Surgical
      Treatment.

PMID- 29646509
TI  - On the Etiology of Stricture of the Urethra.

PMID- 29646510
TI  - Naval Medical Department.

PMID- 29646512
TI  - Mortality in Paris.

PMID- 29646511
TI  - Army Medical Service.-Assistant Surgeons.

PMID- 29646513
TI  - On Civil Incapacity.

PMID- 29646514
TI  - On Dropsy of the Ovum.

PMID- 29646515
TI  - Case of Lithotomy in the Forfar Infirmary.

PMID- 29646516
TI  - Midwifery.

PMID- 29646517
TI  - On the Comparative Frequency of Twin-Bearing in Different Pregnancies.

PMID- 29646519
TI  - Glasgow Medico-Chirurgical Society.

PMID- 29646518
TI  - The Dietary of Scottish Agricultural Labourers.

PMID- 29646520
TI  - Materia Medica and Dietetics.

PMID- 29646521
TI  - On the Influence Which Consanguinity in the Parentage Exercises on the Offspring.

PMID- 29646523
TI  - Conversazione of the Royal College of Surgeons.

PMID- 29646522
TI  - On the Physiology and Pathology of Certain Forms of Dilated Pupil.

PMID- 29646524
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29646525
TI  - On the Nature and Treatment of Uraemic Convulsions.

PMID- 29646526
TI  - General Council of Medical Education and Registration.

PMID- 29646528
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29646527
TI  - The Modern Practice of Medicine: A Lecture Delivered before the Royal College of
      Surgeons.

PMID- 29646530
TI  - The Weather of May in Its Relation to Health.

PMID- 29646529
TI  - Practice of Medicine.

PMID- 29646531
TI  - Climacteric Insanity.

PMID- 29646532
TI  - Virchow and the Cellular Pathology.

PMID- 29646533
TI  - A Case of Traumatic Tetanus Treated by Opium Smoking and Internal Administration
      of Chloroform and Hemp.

PMID- 29646534
TI  - On Some Malformations of the Organs of Generation.

PMID- 29646535
TI  - Abstract of Movement of Medical Profession: As per Scottish Local Medical
      Register.

PMID- 29646537
TI  - Proceedings of the Edinburgh Obstetrical Society.

PMID- 29646536
TI  - Case of Acute Strumous Laryngitis.

PMID- 29646538
TI  - Conversazione of the Royal College of Surgeons.

PMID- 29646539
TI  - On the Metal Indium and Recent Discoveries on Spectrum Analysis.

PMID- 29646540
TI  - Death from Rupture of Varicose Veins in the Lower Extremities.

PMID- 29646541
TI  - Letter from Henry Lee, Esq.

PMID- 29646542
TI  - Surgery.

PMID- 29646543
TI  - Physiology.

PMID- 29646545
TI  - University of Edinburgh.

PMID- 29646544
TI  - Notes on a Case of Paralysis Following Diphtheria.

PMID- 29646546
TI  - Syphilization.

PMID- 29646547
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29646548
TI  - Proceedings of the Edinburgh Obstetrical Society.

PMID- 29646549
TI  - Letter from Professor J. Y. Simpson, M.D.

PMID- 29646550
TI  - On Some Laws of the Production of Twins.

PMID- 29646551
TI  - Notes on the Early History of Midwifery.

PMID- 29646552
TI  - On the Influence Which Consanguinity in the Parentage Exercises upon the
      Offspring.

PMID- 29646553
TI  - Case of Foreign Body in the OEsophagus of an Idiot.

PMID- 29646554
TI  - On the Characters of the Expectoration in Cases of Fetid Bronchitis and Gangrene
      of the Lung.

PMID- 29646555
TI  - General Council of Medical Education and Registration.

PMID- 29646556
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29646557
TI  - On the Statistics of Puerperal Insanity as Observed in the Royal Edinburgh
      Asylum, Morningside.

PMID- 29646558
TI  - Notes on Fetid Bronchitis, and Other Lung-Diseases with Fetid Breath.

PMID- 29646559
TI  - Case of an Unusual Form of Nervous Disease, Dystaxia or Pseudo-Paralysis Agitans,
      with Remarks.

PMID- 29646560
TI  - A Description of a New Form of Uterine Support in Prolapsus.

PMID- 29646561
TI  - Proceedings of the Edinburgh Obstetrical Society.

PMID- 29646562
TI  - Royal Infirmary of Edinburgh.

PMID- 29646563
TI  - Observations on Contemporary French Surgery.

PMID- 29646565
TI  - Questions at the Second Examination for the Degree of Bachelor of Medicine,
      Oxford, December 2, 1864.

PMID- 29646564
TI  - Rickets and Its Pathology Clinically Considered.

PMID- 29646566
TI  - The Medical Warrant for India.

PMID- 29646567
TI  - On Some Malformations of the Organs of Generation.

PMID- 29646569
TI  - Royal College of Physicians.

PMID- 29646568
TI  - On the Closure of Congenital Fissures in the Hard and Soft Palates.

PMID- 29646570
TI  - Typhoid Fever in Penicuik.

PMID- 29646571
TI  - The Arsenic-Eaters of Styria.

PMID- 29646572
TI  - Army Medical Department.

PMID- 29646573
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29646574
TI  - Practice of Medicine.

PMID- 29646576
TI  - Notes on the Medical Organization of the Army of the Potomac.

PMID- 29646575
TI  - A Critical Inquiry Regarding Superfoetation, with Cases.

PMID- 29646577
TI  - On Fetid Expectoration.

PMID- 29646578
TI  - Royal Infirmary.

PMID- 29646579
TI  - Introductory Lecture in the Summer Class of Clinical Surgery: Delivered at the
      Royal Infirmary, on 4th May 1865.

PMID- 29646581
TI  - On the Influence Which Consanguinity in the Parentage Exercises on the Offspring.

PMID- 29646580
TI  - Observations on Some of the Changes Which Take Place after Re-Section of Bones
      and Joints.

PMID- 29646582
TI  - The Actions of the Bromide of Potassium upon the Nervous System.

PMID- 29646583
TI  - Report of the Trial of Alexander Thomson for the Crime of Murder: In Which the
      Defence of Insanity at the Time of the Act Was Sustained.

PMID- 29646584
TI  - Case of Puerperal Convulsions Successfully Treated by the Inhalation of
      Chloroform.

PMID- 29646586
TI  - Military Surgery in France.

PMID- 29646585
TI  - On a New Remedy for Dysentery.

PMID- 29646587
TI  - General Council of Medical Education and Registration.

PMID- 29646588
TI  - General Council of Medical Education and Registration.

PMID- 29646589
TI  - Erratum.
AB  - [This corrects the article on p. 444 in vol. 4.].

PMID- 29646590
TI  - On the Comparative Influence of the Male and Female Parent upon the Progeny.

PMID- 29646591
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29646592
TI  - Surgery.

PMID- 29646593
TI  - Half-Yearly Medical Report of Fife County Prison, Ending June 30, 1858.

PMID- 29646594
TI  - Quarterly Report of Cases Occurring at the Edinburgh Eye Infirmary.

PMID- 29646595
TI  - On the Contractions of the Uterus.

PMID- 29646596
TI  - Trial of a Surgeon for Malpraxis.

PMID- 29646598
TI  - Note of a Case of Rupture of the Ovary, Following Abortion.

PMID- 29646597
TI  - Notes of Cases from the Kidderpore Hospital, Calcutta.

PMID- 29646599
TI  - Varieties.

PMID- 29646600
TI  - Report of the Trial of William Reid for Abortion and Murder.

PMID- 29646601
TI  - Result of Mr Syme's Amputation.

PMID- 29646602
TI  - Case of Ileus.

PMID- 29646603
TI  - Medical Jurisprudence.

PMID- 29646604
TI  - Therapeutical Record.

PMID- 29646605
TI  - Medicine.

PMID- 29646606
TI  - Lunacy Amendment Act.

PMID- 29646607
TI  - Quarterly Return of Births, Deaths, and Marriages.

PMID- 29646608
TI  - Medical Notes from the Continent: Or, Sketches of the Universities, Hospitals,
      Lunatic Asylums, and Mineral Baths of Holland, Belgium, Germany, and Austria.

PMID- 29646609
TI  - Case of Aneurism of the Arch of the Aorta, Complicated with Tubercle and
      Hemiplegia, Terminating by Rupture into the Pericardium.

PMID- 29646610
TI  - Remarks on the Changes Which Are Supposed to Have Taken Place in the Type of
      Continued Fever.

PMID- 29646611
TI  - Cretinism.

PMID- 29646612
TI  - Cases of Aneurism Treated Unsuccessfully by Compression.

PMID- 29646613
TI  - On the Use of Chloroform in Spasmodic Diarrhoea.

PMID- 29646614
TI  - Erratum.
AB  - [This corrects the article on p. 75 in vol. 4.].

PMID- 29646615
TI  - Case of Ligature of the Brachial Artery, Illustrating the Persistent Vitality of
      the Tissues.

PMID- 29646616
TI  - Varieties.

PMID- 29646618
TI  - The Medical Act.

PMID- 29646617
TI  - Case of Cancerous Tumour Treated by Chloride of Zinc.

PMID- 29646619
TI  - The Pathology of Miners' Lung.

PMID- 29646620
TI  - The Fordoun Case.

PMID- 29646621
TI  - Ununited Fracture of Fore-Arm of Seventeen Months Standing.-Operation-Cure.

PMID- 29646622
TI  - Removal of a Cancerous Tumour from below the Tongue, with Some Remarks on the
      Operative Surgery of the Tongue.

PMID- 29646623
TI  - Association of Medical Officers of Asylums and Hospitals for the Insane.

PMID- 29646624
TI  - Graduation Address: August 1858.

PMID- 29646625
TI  - British Medical Association.

PMID- 29646627
TI  - Army Sanitary Report.

PMID- 29646626
TI  - Medical Notes from the Continent: Or, Sketches of the Universities, Hospitals,
      Lunatic Asylums, and Mineral Baths of Holland, Belgium, Germany, and Austria.

PMID- 29646628
TI  - Hematophobia: A Historical Sketch. With Special Reference to the Treatment of
      Pneumonia.

PMID- 29646630
TI  - A Case of Diseased Cricoid Cartilage.

PMID- 29646629
TI  - The Melanosis of Miners; or, Spurious Melanosis.

PMID- 29646631
TI  - Varieties.

PMID- 29646632
TI  - Quarterly Report of Cases Occurring at the Edinburgh Eye Infirmary.

PMID- 29646633
TI  - Case of Vesico-Vaginal Fistula, with Anteversion and Incarceration of the Cervix
      Uteri in the Bladder. Replacement of the Uterus, and Closure of the Fistulous
      Opening, by Means of the "Button Suture."

PMID- 29646634
TI  - Medical Notes from the Continent: Or, Sketches of the Universities, Hospitals,
      Lunatic Asylums, and Mineral Baths of Holland, Belgium, Germany, and Austria.

PMID- 29646635
TI  - A Quack Doctor's Letter.

PMID- 29646636
TI  - Medicine.

PMID- 29646637
TI  - Cases in Surgical Practice.

PMID- 29646638
TI  - Course of Study Required by the Various Boards of the United Kingdom.

PMID- 29646639
TI  - Report of the Depot Hospital at Umballa, from 28th May 1857 to 31st March 1858.

PMID- 29646640
TI  - Miner's Bronchitis, or Spurious Melanosis.

PMID- 29646642
TI  - The Fordoun Case.

PMID- 29646641
TI  - On the Nomenclature and Classification of Continued Fevers.

PMID- 29646643
TI  - Medical Schools of Scotland, 1858-9.

PMID- 29646644
TI  - Clinical Illustrations of the Pathology and Treatment of Delirium Tremens.

PMID- 29646645
TI  - Two Cases of Aneurism of the Abdominal Aorta.

PMID- 29646646
TI  - Large Fibrous Tumour of Uterus: Enucleation and Expulsion-Recovery.

PMID- 29646647
TI  - Medicine.

PMID- 29646648
TI  - Cancer of the Stomach, as Illustrated by Cases in Dr W. T. Gairdner's Wards at
      the Edinburgh Royal Infirmary, during the Winter Session 1857-58.

PMID- 29646649
TI  - Memorial of the Royal College of Physicians of Edinburgh.

PMID- 29646650
TI  - Adherent Pericardium.

PMID- 29646651
TI  - Note of the Result of an Analysis of a Portion of the Bread with Which A-Lum Was
      Accused of Poisoning the European Residents at Hong-Kong.

PMID- 29646652
TI  - On the Proclivity to Phthisis Commonly Ascribed to Persons of Xanthous
      Complexion.

PMID- 29646653
TI  - Our Medical Session.

PMID- 29646655
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29646654
TI  - Statement by Medical Lecturers in Edinburgh, in Reference to the Bill of the
      Right Hon. W. F. Cowper, on Medical Reform.

PMID- 29646656
TI  - Curious Case of Twins, in Which the Cord of One Child Was Encircled by a Knot on
      the Cord of the Other Child.

PMID- 29646657
TI  - Half-Yearly Report of Cases Occurring at the Edinburgh Eye Infirmary.

PMID- 29646658
TI  - On the Changes Which Have Taken Place in the Constitution of Fevers and
      Inflammations in Edinburgh during the Last Forty Years.

PMID- 29646659
TI  - Varieties.

PMID- 29646660
TI  - The Therapeutic Relations of Opium and Belladonna to Each Other.

PMID- 29646661
TI  - Registration Act.

PMID- 29646662
TI  - Skoda's Statistics and Their Critic.

PMID- 29646663
TI  - Medicine.

PMID- 29646664
TI  - History of a Case in Which Inflammatory Softening Existed in a Limited Portion of
      the Spinal Marrow.

PMID- 29646665
TI  - Varieties.

PMID- 29646666
TI  - A Case of Cynanche Maligna-Tracheotomy Performed.

PMID- 29646667
TI  - On OEstrus or Affectio Bovina.

PMID- 29646668
TI  - Surgery.

PMID- 29646669
TI  - Propositions Concerning the Lues Venerea, with a Commentary.

PMID- 29646670
TI  - Royal College of Surgeons.

PMID- 29646671
TI  - Case of Poisoning with Strychnia.

PMID- 29646672
TI  - Erratum.
AB  - [This corrects the article on p. 226 in vol. 4.].

PMID- 29646673
TI  - Therapeutical Record.

PMID- 29646675
TI  - The Fellowship of the College of Surgeons.

PMID- 29646674
TI  - The Medical Council.

PMID- 29646676
TI  - Case of Sun-Stroke-Exposure for Thirty Hours-Recovery.

PMID- 29646677
TI  - Rank of Army Surgeons.

PMID- 29646678
TI  - Note on the Incubation of Guinea Worm (Filaria Medinensis.).

PMID- 29646679
TI  - Demonstration of the Use of the Round Ligament of the Hip Joint.

PMID- 29646681
TI  - Localized Vasodilatation.

PMID- 29646680
TI  - Painless Dental Surgery.

PMID- 29646682
TI  - The Symptomatology of Diabetes Mellitus: An Analysis of 1700 Cases.

PMID- 29646683
TI  - Syphilis of the Stomach.

PMID- 29646684
TI  - Tuberculous Meningitis in Pregnancy.

PMID- 29646685
TI  - Notes.

PMID- 29646686
TI  - Radiocarcinoma and Radium.

PMID- 29646687
TI  - A Study of the AEtiology of Acute Rheumatism, with Special Reference to the
      Relationship of the Haemolytic Streptococcus to the Disease.

PMID- 29646688
TI  - Primary Carcinoma of the Fossa Navicularis.

PMID- 29646689
TI  - A Comparison of the Wassermann, Kline, and Meinicke Tests for Sera.

PMID- 29646690
TI  - Epilepsy and Dehydration.

PMID- 29646692
TI  - The Treatment of Megacolon by Parathormone.

PMID- 29646691
TI  - OEdema as Influenced by a Low Ratio of Sodium to Potassium Intake.

PMID- 29646693
TI  - OEsophagetasia.

PMID- 29646694
TI  - The Prediction of Sex in the Unborn.

PMID- 29646695
TI  - Post-Traumatic Parotid Hyperhydrosis.

PMID- 29646696
TI  - Congenital Defects of the Lung.

PMID- 29646697
TI  - Homoiotransplantation of the Ovary.

PMID- 29646698
TI  - Congenital Epulis.

PMID- 29646699
TI  - Studies in Urinary Infection-Pathological, Therapeutic, and Bacteriological.

PMID- 29646700
TI  - The Need of a Course in Medical Genetics in the Medical Curriculum: A Pivotal
      Point in the Eugenic Programme.

PMID- 29646701
TI  - Report of an Investigation into an Outbreak of Infectious Jaundice.

PMID- 29646702
TI  - The Influence of Gerson Regime on Pulmonary Tuberculosis.

PMID- 29646703
TI  - Precocious Puberty in the Female in Association with Chorion-Carcinoma of the
      Ovary.

PMID- 29646704
TI  - Dermatitis Due to Shoe Leather.

PMID- 29646705
TI  - Latent Thyreoid Adenocarcinoma.

PMID- 29646706
TI  - Traumatic Rupture of the Spleen in Pregnancy.

PMID- 29646707
TI  - Acute Dermatitis Due to Opium Preparations.

PMID- 29646708
TI  - Corrigan's Original Description of Aortic Regurgitation: A Reference to Some
      Matters of Historical Interest.

PMID- 29646710
TI  - Submandibular Sialolithiasis.

PMID- 29646709
TI  - Chronic Alcoholism and Its Treatment.

PMID- 29646711
TI  - Bullous Dermatosis Due to Sun-Bathing in Meadows.

PMID- 29646712
TI  - The Fat-Soluble Vitamins-Their Significance in Nutrition.

PMID- 29646713
TI  - Some Disorders of Speech in Childhood: Their Nature and Treatment.

PMID- 29646714
TI  - The Ketogenic Treatment of Urinary Infections.

PMID- 29646716
TI  - Mind and Medicine.

PMID- 29646715
TI  - Sir John Eliot, Bart., M.D., of Peebles, and Some of His Friends.

PMID- 29646717
TI  - Dermatitis Due to Jewellery.

PMID- 29646718
TI  - Hypophysial Dysostosis.

PMID- 29646719
TI  - The Treatment of Tuberculous Disease of the Kidney from the Standpoint of the
      Surgeon.

PMID- 29646720
TI  - Our Progress in the Prevention and Treatment of Tuberculosis.

PMID- 29646722
TI  - Parathyreoid Osteodystrophy (Osteitis Fibrosa).

PMID- 29646721
TI  - Robert Koch's Discovery of the Tubercle Bacillus: Some of Its Implications and
      Results.

PMID- 29646723
TI  - Results of Examination for Tubercle Bacillus of 1500 Samples of Milk in Dundee.

PMID- 29646725
TI  - Lung Collapse Therapy.

PMID- 29646724
TI  - Bronchial Asthma and Pulmonary Tuberculosis.

PMID- 29646727
TI  - Abdominal Glandular Tuberculosis-A Study with Special Reference to Faecal Fat
      Content.

PMID- 29646726
TI  - Seasonal Variation in Tuberculosis, as Illustrated by a Study of Pus Formation in
      Tuberculous Glands.

PMID- 29646728
TI  - The Orientation of Medical Education.

PMID- 29646729
TI  - Notes.

PMID- 29646730
TI  - Trigeminal Neuralgia.

PMID- 29646731
TI  - Carcinoma in the Mammary Lobule and Its Origin.

PMID- 29646732
TI  - Spontaneous Pneumothorax in Infants.

PMID- 29646733
TI  - Carcinoma of the Cervix.

PMID- 29646735
TI  - Telangiectasis in the Great Trochanter.

PMID- 29646736
TI  - Clinical Meeting.

PMID- 29646734
TI  - A Series of Tumours of the Nervous System Classified According to Modern Methods.

PMID- 29646737
TI  - Intervertebral Cysts.

PMID- 29646738
TI  - Pneumoperitoneum.

PMID- 29646739
TI  - An Unusual Bronchobiliary Fistula.

PMID- 29646740
TI  - Studies in the Nephrotic Syndrome.

PMID- 29646741
TI  - Notes.

PMID- 29646742
TI  - Dysembryoma of the Great Omentum.

PMID- 29646743
TI  - Individual Variation in the Response to Drugs.

PMID- 29646744
TI  - Neuropathic Dilatation of the OEsophagus.

PMID- 29646745
TI  - Muscle-Tonus and the Circulation.

PMID- 29646746
TI  - Clinical Meeting.

PMID- 29646748
TI  - Loose Bodies in the Tunica Vaginalis Testis.

PMID- 29646747
TI  - Heredity in Cancer, and Its Value as an Aid in Early Diagnosis.

PMID- 29646750
TI  - Enteric-Fever Cholecystitis.

PMID- 29646749
TI  - Osteodystrophia and Parathyreoidectomy.

PMID- 29646751
TI  - Simple Tumours of the Lung.

PMID- 29646753
TI  - Unusual Tumour of the Common Bile-Duct.

PMID- 29646752
TI  - Splenic Anaemia.

PMID- 29646754
TI  - Capillary Regeneration.

PMID- 29646755
TI  - Notes.

PMID- 29646756
TI  - Congenital Dilatation of the Common Bile-Duct.

PMID- 29646758
TI  - Agranulocytosis.

PMID- 29646757
TI  - Pernicious Anaemia: Some Considerations in Regard to Its Nature and Pathogenesis.

PMID- 29646760
TI  - An Unusual Tumour of the Tongue.

PMID- 29646759
TI  - Alexander Hughes Bennett and the First Recorded Case in Which an Intracranial
      Tumour Was Removed by Operation.

PMID- 29646761
TI  - Retropharyngeal Lipoma.

PMID- 29646762
TI  - Traumatic Pneumatocephalus.

PMID- 29646763
TI  - Individual Variation in the Response to Drugs.

PMID- 29646764
TI  - The Innervation of the Distal Colon.

PMID- 29646765
TI  - Tendon Sheath Tumours.

PMID- 29646766
TI  - Madame Curie.

PMID- 29646767
TI  - A Suggested Hypothesis of Kidney Mechanism.

PMID- 29646768
TI  - Treatment of Pharyngeal Diverticula.

PMID- 29646769
TI  - Intertarsal Developmental Ankylosis.

PMID- 29646770
TI  - Pre-Operative Medication.

PMID- 29646771
TI  - Lupus Carcinoma.

PMID- 29646772
TI  - Sir Charles Bell: A Brief Sketch of His Life and Work.

PMID- 29646774
TI  - Codliver Oil Dressing for Wounds and Burns.

PMID- 29646773
TI  - Lobar Pneumonia and Its Serological Treatment.

PMID- 29646775
TI  - Tetany and Sympathectomy.

PMID- 29646777
TI  - Fibroma of the Vagina.

PMID- 29646776
TI  - Primary Carcinoma of the Liver in a Child.

PMID- 29646778
TI  - Abscess of the Lung.

PMID- 29646780
TI  - Innervation of Cicatrices.

PMID- 29646779
TI  - Insulin Requirements of Diabetic Out-Patients.

PMID- 29646781
TI  - Recurrent Dislocation at the Shoulder.

PMID- 29646782
TI  - Scoliotic Vertebral Osteosis.

PMID- 29646783
TI  - Orbitonasal Meningocele.

PMID- 29646784
TI  - Anatomy of "The Splits".

PMID- 29646785
TI  - Some Aspects of Acute Lobar Pneumonia, with Special Reference to Serum Therapy.

PMID- 29646786
TI  - Two Cases of Diaphragmatic Hernia.

PMID- 29646787
TI  - Renal Tuberculosis : I. Histopathology and Pathogenesis.

PMID- 29646788
TI  - The School Medical History of Persons Who Develop Pulmonary Tuberculosis in Young
      Adult Life.

PMID- 29646789
TI  - Renal Tuberculosis : II. The Bacteriological Characteristics of the Tubercle
      Bacilli.

PMID- 29646790
TI  - Variabilite du Virus Tuberculeux.

PMID- 29646791
TI  - Variations du Virus Tuberculeux dans les Cultures Homogenes: Les " bacilles nus "
      de la tuberculose in vitro et in vivo.

PMID- 29646792
TI  - Variations Biologiques du Virus Tuberculeux.

PMID- 29646793
TI  - Biological Variations in the Tubercle Virus.

PMID- 29646794
TI  - Meningeal Tuberculosis: Bacteriology and Pathology.

PMID- 29646795
TI  - Cerebro-Spinal Fluid in Tuberculous Meningitis.

PMID- 29646796
TI  - Meningeal Tuberculosis.

PMID- 29646797
TI  - Meningeal Tuberculosis as a Terminal Feature in Pulmonary Tuberculosis.

PMID- 29646798
TI  - Biologische Veranderungen des Tuberkulose Erregers.

PMID- 29646799
TI  - Acute Pneumonic Phthisis : Report on Three Cases in Which Treatment by Artificial
      Pneumothorax Was Attempted.

PMID- 29646800
TI  - Some Observations on the Variations of the Tuberculosis Virus.

PMID- 29646801
TI  - Variations Biologiques du Virus Tuberculeux.

PMID- 29646802
TI  - Musings in the Garden: Fifty Years' Association with the Tubercle Bacillus.

PMID- 29646803
TI  - Meningeal Tuberculosis: Seasonal, Age, and Sex Incidence.

PMID- 29646804
TI  - Ninth Conference of the International Union against Tuberculosis, Warsaw, 4th to
      6th September 1934.

PMID- 29646805
TI  - Variations Biologiques du Virus Tuberculeux.

PMID- 29646806
TI  - Variations Biologiques du Virus Tuberculeux.

PMID- 29646807
TI  - Variabilite Biologique du Virus Tuberculeux.

PMID- 29646808
TI  - Three Cases of Tuberculosis of the Central Nervous System Followed by Apparent
      Clinical Recovery.

PMID- 29646809
TI  - Renal Tuberculosis : III. Tubercle Bacilluria and Its Significance.

PMID- 29646810
TI  - The Occurrence of the Different Groups of Haemolytic Streptococci in Human
      Infections.

PMID- 29646811
TI  - The Care and Cure of the Crippled Child in the South-East of Scotland: An Account
      of the Princess Margaret Rose Hospital, Fairmilehead, Edinburgh, and Its
      Associated Clinics.

PMID- 29646813
TI  - Cancer of the Mouth and Jaws.

PMID- 29646812
TI  - A Microscopical Inquiry into the AEtiology of Poliomyelitis with a Note on
      Chronic Encephalitis Lethargica.

PMID- 29646814
TI  - Clinical Meeting.

PMID- 29646815
TI  - The Radiological Treatment of Breast Cancer and Its Metastases.

PMID- 29646816
TI  - Tuberculosis of the Lungs in Childhood: Problems and Results of Treatment.

PMID- 29646817
TI  - The Effect of P-Amino-Benzene-Sulphonamide upon Various Bacteria in Vitro and in
      Vivo.

PMID- 29646818
TI  - Clinical Meeting.

PMID- 29646819
TI  - Some Reflections on the Pathogenesis and Treatment of Cancer of the Breast.

PMID- 29646820
TI  - Pulmonary Tuberculosis in Children, with Special Reference to the Adult Types of
      the Disease.

PMID- 29646821
TI  - Medical Education in Scotland.

PMID- 29646822
TI  - Passages of Medical History. Edinburgh Medicine from 1860.

PMID- 29646823
TI  - The Periodicity of Influenza.

PMID- 29646824
TI  - Gastroscopy.

PMID- 29646825
TI  - Disseminated Sclerosis: A Review of Modern Work on Its AEtiology.

PMID- 29646826
TI  - Notes.

PMID- 29646827
TI  - Cancer and Its Biochemical Factors.

PMID- 29646828
TI  - The Surgical Treatment of Coronary Disease.

PMID- 29646829
TI  - Notes.

PMID- 29646830
TI  - Recent Developments in the Surgery of Obstructive Jaundice, with Special
      Reference to the Risk of Haemorrhage.

PMID- 29646831
TI  - Metabolism of the Heart.

PMID- 29646833
TI  - Chronic Hypertrophic Emphysema. Its AEtiology and the Cause of Some of Its Signs
      and Symptoms.

PMID- 29646832
TI  - The Acute Abdomen in Childhood.

PMID- 29646834
TI  - Post-Traumatic Carotid-Cavernous Arteriovenous Fistula.

PMID- 29646835
TI  - Late Effects of Head Injury.

PMID- 29646836
TI  - Traumatic Epilepsy.

PMID- 29646837
TI  - Visual Disturbances in Cases of Head Injury.

PMID- 29646839
TI  - Mass Attack on Chronic Arthritis.

PMID- 29646838
TI  - Some Ideals and the Business of Healing.

PMID- 29646840
TI  - The Mechanism of Megaloblastic Blood Formation.

PMID- 29646841
TI  - Changes in Blood Chemistry after Burning Injuries and in Other Grave Surgical
      Conditions; with Some Reference to Treatment by Desoxycorticosterone Acetate.

PMID- 29646842
TI  - Surgical Aspects of the Treatment of Toxic Goitre : Observations Based on a
      Series of 243 Cases.

PMID- 29646843
TI  - Notes on the Surgery of the Newborn. The Foetal Atresiae.

PMID- 29646844
TI  - Debatable Tumours in Human and Animal Pathology-VIII. Melanoma.

PMID- 29646845
TI  - If Health Be Wanting.

PMID- 29646846
TI  - Varieties.

PMID- 29646847
TI  - Statistics of Prisoners: Their Death-Rate and Their Diseases.

PMID- 29646848
TI  - On the Determination of the Proportion of Solids in the Urine of Health and
      Disease.

PMID- 29646850
TI  - The Ordinances of the Universities Commissioners for Medical Degrees.

PMID- 29646849
TI  - Hospital for Sick Children at Lisbon.

PMID- 29646851
TI  - Description of a Case of Double Uterus.

PMID- 29646853
TI  - Notes on the Baths of the Salzkammergut, and on the Route to Vienna by the
      Danube.

PMID- 29646852
TI  - Medicine.

PMID- 29646855
TI  - General Council of Medical Education and Registration.

PMID- 29646854
TI  - Scottish Universities Commission.

PMID- 29646856
TI  - Toxicology.

PMID- 29646857
TI  - Medical Act (1858) Amendment Bill.

PMID- 29646858
TI  - The Ordinances of the Universities Commissioners Regarding Medical Degrees.

PMID- 29646859
TI  - Medicine.

PMID- 29646860
TI  - Notes on the Surgery of the Indian Campaign of 1857-58.

PMID- 29646861
TI  - Observations on the Trichina Spiralis.

PMID- 29646863
TI  - Hygiene.

PMID- 29646862
TI  - Surgery.

PMID- 29646864
TI  - On the Alteration of Pitch of Cardiac Murmurs by Conduction through the Various
      Media Composing the Thoracic Organs and Walls.

PMID- 29646865
TI  - Graduation in Medicine at the University of Edinburgh.

PMID- 29646866
TI  - General Council of Medical Education and Registration.

PMID- 29646867
TI  - Observations on Typhus and Typhoid Fevers as Seen in Dublin.

PMID- 29646868
TI  - Varieties.

PMID- 29646869
TI  - Quarterly Return of Births, Deaths, and Marriages.

PMID- 29646870
TI  - Questions at the Last Examination of Army Assistant-Surgeons before Promotion.

PMID- 29646871
TI  - Toxicology.

PMID- 29646873
TI  - Varieties.

PMID- 29646872
TI  - Notes on the Surgery of the Indian Campaign of 1857-58.

PMID- 29646874
TI  - Quarterly Report of Cases Occurring at the Edinburgh Eye Infirmary, 140, George
      Street.

PMID- 29646875
TI  - On the Manufacture of Castor Oil at Dinapore.

PMID- 29646876
TI  - Table of Preliminary Examinations of the Various Medical Licensing Bodies.

PMID- 29646877
TI  - Statistics of Prisoners: Their Diseases and General Health.

PMID- 29646878
TI  - On Delirium Tremens.

PMID- 29646879
TI  - Remarks upon the Birth-Rate as Affecting the Proportion of Deaths under Five
      Years of Age.

PMID- 29646880
TI  - Questions at the Last Examination of Candidates for Army Assistant-Surgeoncies.

PMID- 29646881
TI  - Medical Schools of Scotland, 1860-61.

PMID- 29646883
TI  - Case of Rupture of Ascending Aorta.

PMID- 29646882
TI  - Introductory Address, Delivered at the Edinburgh Medical and Surgical School,
      Surgeons' Hall, at the Opening of the Session 1859-60.

PMID- 29646885
TI  - Course of Study Required by the Various Boards of the United Kingdom.

PMID- 29646884
TI  - List of Hospitals, Dispensaries, Etc., in Connection with the Medical Schools of
      Scotland.

PMID- 29646886
TI  - Midwifery.

PMID- 29646887
TI  - Surgery.

PMID- 29646888
TI  - Medicine.

PMID- 29646889
TI  - Report on the Loss of Limbs, as Affecting Longevity, among the Pensioners at the
      Royal Hospital, Greenwich.

PMID- 29646891
TI  - University of St Andrews.

PMID- 29646890
TI  - Medical Education. When Does Professional Study Begin?

PMID- 29646892
TI  - Irish Branch Council of Medical Education and Registration.

PMID- 29646893
TI  - On Infantile Mortality, as Illustrated by Private Practice; with Suggestions for
      Future Inquiries.

PMID- 29646894
TI  - On the Use of Plaster of Paris Bandages for Dressing Stumps after Amputation.

PMID- 29646895
TI  - Cholera at Gibraltar.

PMID- 29646896
TI  - Surgical Cases and Observations.

PMID- 29646897
TI  - Royal College of Surgeons.

PMID- 29646898
TI  - Proceedings of the Edinburgh Obstetrical Society.

PMID- 29646899
TI  - Additional Remarks on the Birth-Rate as Affecting the Mortality of Children under
      Five Years of Age.

PMID- 29646900
TI  - Medicine.

PMID- 29646901
TI  - Variety.

PMID- 29646902
TI  - Report of Clinical Cases Treated during the Session 1859-60, in the Surgical
      Wards of the Royal Infirmary.

PMID- 29646903
TI  - Opening of the Army Medical School.

PMID- 29646904
TI  - Medical Constitution of the Spring and Summer of 1860 in France.

PMID- 29646905
TI  - The Army in China.

PMID- 29646906
TI  - Surgery.

PMID- 29646907
TI  - Dental Surgery as an Adjunctive Branch at Our Medical Schools: From a Lecture
      Delivered at the Medical School, Surgeons' Hall, May 1860.

PMID- 29646908
TI  - Midwifery.

PMID- 29646909
TI  - Case of Intra-Uterine Small-Pox.

PMID- 29646910
TI  - Retirement of M. Ricord from the Hospital Du Midi.

PMID- 29646911
TI  - Description of Two Pathological Preparations, Exhibiting Rupture of the Uterus
      from Malignant Disease, and Peculiar Disease of the Ovaries with Peritoneo-Rectal
      Fistula.

PMID- 29646912
TI  - Dinner to the Medical Officers of the Channel Squadron.

PMID- 29646913
TI  - A Pioneer in Tropical Medicine.

PMID- 29646914
TI  - The Surgery of Blood Vessels.

PMID- 29646915
TI  - The Early Stages of Leukaemia.

PMID- 29646916
TI  - The Laevulose Tolerance Test in Childhood.

PMID- 29646917
TI  - The Fate in the Body of Sulphapyridine.

PMID- 29646918
TI  - Dermatitis from Grapes.

PMID- 29646919
TI  - The Problem of the Virulence of the Tubercle Bacillus.

PMID- 29646920
TI  - Lip-Stick Dermatitis.

PMID- 29646922
TI  - The Treatment of Subacute Bacterial Endocarditis.

PMID- 29646921
TI  - Occupational Therapy.

PMID- 29646923
TI  - Nickel Eczema.

PMID- 29646924
TI  - Nicotinic Acid Treatment of Pellagra: With Report of a Case Occurring in
      Edinburgh.

PMID- 29646925
TI  - Tuberculous Pyo-Pneumothorax, with Special Reference to Certain Points in Its
      Management.

PMID- 29646926
TI  - Accidental Tattooing of the Face.

PMID- 29646927
TI  - Protruded Intravertebral Disc.

PMID- 29646928
TI  - The Dynamics of Crowd Infection.

PMID- 29646929
TI  - On Thrush, with Special Reference to Vaginal Thrush.

PMID- 29646931
TI  - The Pathology of Speech and Voice.

PMID- 29646930
TI  - The Use of OEstrogens in Obstetrics and Gynaecology.

PMID- 29646932
TI  - Some Aspects of the Malnutrition Problem.

PMID- 29646933
TI  - Dysmenorrhoea.

PMID- 29646934
TI  - Physical Education in the University of Edinburgh.

PMID- 29646935
TI  - Manifestations of Tuberculosis in Ophthalmic Practice.

PMID- 29646937
TI  - Psychosomatic Medicine.

PMID- 29646938
TI  - The Laevulose Tolerance Test in Intolerance to Anti-Syphilitic Therapy.

PMID- 29646936
TI  - Observations on the Treatment of Severe Haematemesis and Melaena.

PMID- 29646939
TI  - The Care of Children in War-Time and after.

PMID- 29646940
TI  - Ergot and Its Alkaloids.

PMID- 29646941
TI  - Intra-Abdominal Diagnosis.

PMID- 29646943
TI  - Notes.

PMID- 29646942
TI  - Hyperemesis Gravidarum.

PMID- 29646944
TI  - The Diagnosis of Cancer of the Breast.

PMID- 29646945
TI  - A Hundred Years Ago: German Measles.

PMID- 29646946
TI  - Artificial Pneumoperitoneum Applied to Certain Therapeutic Problems in Pulmonary
      Tuberculosis.

PMID- 29646947
TI  - Action of Acetylsalicylic Acid on Teeth.

PMID- 29646948
TI  - A Study on Allergy in Experimental Tuberculosis.

PMID- 29646949
TI  - Expectorants in Chronic Bronchitis.

PMID- 29646950
TI  - The Role of Zinc Ionisation in the Treatment of Allergy in the Nose.

PMID- 29646951
TI  - On the Contributions of Genetics to Reconstructive Medicine.

PMID- 29646952
TI  - Gas Warfare.

PMID- 29646954
TI  - Notes.

PMID- 29646953
TI  - Iodine and Exophthalmic Goitre.

PMID- 29646955
TI  - A Hundred Years Ago: Chancery Cachexia.

PMID- 29646957
TI  - Etiology and Modern Treatment of Varicose Ulcer.

PMID- 29646956
TI  - The Work of a Regimental Medical Officer.

PMID- 29646958
TI  - Treatment of War Wounds in France May-June 1940.

PMID- 29646959
TI  - Painless Myocardial Infarction.

PMID- 29646960
TI  - Case Record-Chloroma.

PMID- 29646961
TI  - Experimental Hibernation in Metastatic Growths.

PMID- 29646962
TI  - Two Cases of Follicular Lymphoblastoma.

PMID- 29646963
TI  - Notes.

PMID- 29646965
TI  - A Hundred Years Ago. The Reviewing of Books.

PMID- 29646964
TI  - Some Aspects of Streptococcal Infection. A Review.

PMID- 29646966
TI  - Studies on Stored Blood.: I. Results in a Series of 427 Transfusions.

PMID- 29646967
TI  - Effort Syndrome in the Present War.

PMID- 29646968
TI  - Carcinoma of the Stomach in Young Subjects.

PMID- 29646969
TI  - Edinburgh Medical School a Hundred Years Ago.

PMID- 29646970
TI  - Acute Leukaemia: A Clinical and Haematological Study.

PMID- 29646972
TI  - Notes.

PMID- 29646971
TI  - Modern Therapy in Specific Infections.

PMID- 29646973
TI  - Medical Education in Scotland.

PMID- 29646974
TI  - Studies on Stored Blood : III. The Oxygen Capacity of Stored Blood.

PMID- 29646975
TI  - A Hundred Years Ago: Resuscitation.

PMID- 29646976
TI  - Studies on Stored Blood: IV. Modifications in the Equipment for Blood
      Transfusion.

PMID- 29646977
TI  - A Survey of the Biological Types of the Diphtheria Bacillus in Edinburgh, 1932
      1939.

PMID- 29646978
TI  - Debatable Tumours in Human and Animal Pathology: IX. Endothelioma.

PMID- 29646979
TI  - Studies on Stored Blood : II. The Leucocytes in Stored Blood.

PMID- 29646980
TI  - Pediatric Surgery in General Practice.

PMID- 29646981
TI  - The Role of the Luteal Hormone in the Maintenance of Gestation.

PMID- 29646982
TI  - The Treatment of Disseminated Sclerosis as a Deficiency Disease: A Study of Fifty
      Cases.

PMID- 29646983
TI  - The Holmes-Adie Syndrome: A Benign Clinical Entity Which Simulates Syphilis of
      the Nervous System.

PMID- 29646984
TI  - An Investigation into the Sterility of the Droitwich Brine, and Its Bactericidal
      Action.

PMID- 29646985
TI  - Intestinal Obstruction : The Results of Recent Experiment Applied to Clinical
      Practice.

PMID- 29646986
TI  - Clinical Meeting.

PMID- 29646987
TI  - A Gas-Heater Danger.

PMID- 29646988
TI  - Reticuloendothelioma of the Leg.

PMID- 29646989
TI  - Notes.

PMID- 29646990
TI  - The Fats of Human Blood.

PMID- 29646992
TI  - Ganglionectomy in Angina Pectoris.

PMID- 29646991
TI  - Physiology and the Surgeon.

PMID- 29646993
TI  - Salicylates in Rheumatic Fever.

PMID- 29646994
TI  - Sympathectomy for Scleroderma.

PMID- 29646996
TI  - Secondary Rupture of the Spleen.

PMID- 29646995
TI  - Perspiration and the Sympathetic.

PMID- 29646998
TI  - Notes.

PMID- 29646997
TI  - Valedictory Address on "Methods of Examination of the Character of Patients and
      Also Delinquents as a Help in Diagnosis and Treatment".

PMID- 29646999
TI  - Studies in Method and Standardisation of Blood Examination: II. Sedimentation
      Rate and Sedimentation Volume of Blood.

PMID- 29647000
TI  - Hereditary Ocular Pigmentation.

PMID- 29647001
TI  - Displacement of the Gall-Bladder.

PMID- 29647003
TI  - Seborrhoea after Alcoholic Injection for Neuralgia.

PMID- 29647002
TI  - Changing Conceptions of Disease.

PMID- 29647004
TI  - Intraperitoneal Effusion of Bile.

PMID- 29647006
TI  - Acid Ammonium Phosphate as a Urinary Acidifier.

PMID- 29647005
TI  - Fever Therapy: Its Rationale in Diseases of the Nervous System.

PMID- 29647007
TI  - The Effect of Constitutional "Vitality" on Prognosis, as Illustrated by Acute
      Appendicitis.

PMID- 29647008
TI  - Notes on the Diagnosis of Some Febrile Conditions.

PMID- 29647009
TI  - Australian Aerial Medical Service.

PMID- 29647010
TI  - Clinical Meeting.

PMID- 29647011
TI  - Leuco-Erythroblastosis.

PMID- 29647012
TI  - A Note on the Depot Treatment of Pernicious Anaemia.

PMID- 29647013
TI  - The Parenteral Administration of Vitamin B1 in the Treatment of Polyneuritis and
      Other Conditions.

PMID- 29647015
TI  - Alexander Miles: Editor, Edinburgh Medical Journal, 1911-1936.

PMID- 29647014
TI  - Lupus Vulgaris, with Special Reference to Its Treatment with the Finsen-Lomholt
      Lamp.

PMID- 29647016
TI  - Paroxysmal Auricular Tachycardia Associated with a Primary Cardiac Tumour.

PMID- 29647017
TI  - Edinburgh Medicine, 1500-1700.

PMID- 29647018
TI  - Crowd-Psychology as the Modern Menace: A Medico-Sociological Study.

PMID- 29647019
TI  - The Epileptic Fit and the Epilepsies.

PMID- 29647021
TI  - Notes.

PMID- 29647020
TI  - Radiological Examination of the Gastro-Intestinal Tract.

PMID- 29647022
TI  - Experimental Glomerulo-Nephritis Produced by the Use of Specific Sera.

PMID- 29647024
TI  - Loose Bodies in the Pleural Cavity.

PMID- 29647023
TI  - The Practical Application of B.C.G. Vaccine in the Prophylaxis of Tuberculous
      Infection in Children.

PMID- 29647025
TI  - Diagnosis and Treatment of Acute Abdominal Conditions in Children.

PMID- 29647026
TI  - Some Points in the Histological Diagnosis of Tuberculosis.

PMID- 29647027
TI  - An Experimental Study on Allergy and Immunity.

PMID- 29647028
TI  - Mediastinal Neurofibroma.

PMID- 29647029
TI  - Tuberculosis of the Testis.

PMID- 29647030
TI  - Inoculation Tuberculosis. Report of an Unusual Case.

PMID- 29647031
TI  - Notes on a Series of Nephrectomies for Tuberculosis.

PMID- 29647032
TI  - Some Points in the Pathology and Bacteriology of Tuberculosis in Children.

PMID- 29647033
TI  - Lupus Vulgaris : With Special Reference to Its Treatment with the Finsen-Lomholt
      Lamp.

PMID- 29647034
TI  - Avian Type Tubercle Bacillus: Its Characteristics, Cultural and Pathogenic, with
      a Demonstration of Natural Disease Produced by the Bacillus.

PMID- 29647035
TI  - The Role of B.C.G. in the Vaccination of Cattle against Tuberculosis.

PMID- 29647037
TI  - Universal Scleroderma.

PMID- 29647036
TI  - Isolated Fracture of the Lunate Bone.

PMID- 29647038
TI  - Clinical Studies in the Pathology of Bone. No. I.-A Fractured Vertebra.

PMID- 29647040
TI  - A Digital Tophus.

PMID- 29647039
TI  - Pleonosteosis.

PMID- 29647041
TI  - Rupture of the Rectus Abdominis Muscle.

PMID- 29647043
TI  - The Evolution of Ideas Regarding Disease.

PMID- 29647042
TI  - Brucella Infections: With Particular Reference to Undulant Fever in This Country.

PMID- 29647044
TI  - Primary Perirectal Actinomycosis.

PMID- 29647046
TI  - Superimposed Patellae.

PMID- 29647045
TI  - Clinical Studies in the Pathology of Bone. No. III.-A Cicatricial Heterotopic
      Bone.

PMID- 29647047
TI  - The Use and Misuse of Carbohydrates.

PMID- 29647048
TI  - Congenital Atresia of the Cervix Uteri.

PMID- 29647049
TI  - Psoriasis and Arthropathy.

PMID- 29647050
TI  - Parasternal True Hernia of the Diaphragm.

PMID- 29647051
TI  - Spontaneous Pneumoperitoneum.

PMID- 29647052
TI  - Posterior Trephining for Cerebral Effusion.

PMID- 29647054
TI  - Injury and Diabetes.

PMID- 29647053
TI  - A Study of the Lymphogranulomata.

PMID- 29647055
TI  - Carcinoma of the Rectum. An Anatomico-Pathological Study.

PMID- 29647056
TI  - Paralysis of the Recurrent Laryngeal Nerve. A Survey of 235 Cases.

PMID- 29647058
TI  - Fracture of Carpal Navicular.

PMID- 29647057
TI  - Mental Deficiency among Edinburgh School Children.

PMID- 29647059
TI  - Retroperitoneal Wolffian Cyst.

PMID- 29647060
TI  - Rupture of OEsophagus.

PMID- 29647062
TI  - Notes.

PMID- 29647061
TI  - Congenital Vascular Calcinosis.

PMID- 29647063
TI  - Clinical Studies in the Pathology of Bone. No. II.-Localized Unilateral
      Spondylitis.

PMID- 29647064
TI  - Medical Education in Scotland.

PMID- 29647065
TI  - Prognosis in Mammary Carcinoma: Its Relation to Clinical and Histological Grading
      and to Treatment.

PMID- 29647066
TI  - Agranulocytosis.

PMID- 29647067
TI  - Primitive Abdominal Surgery.

PMID- 29647068
TI  - Leiomyoma of Rectovaginal Septum.

PMID- 29647069
TI  - Chorea: A Short Study of 200 Cases.

PMID- 29647070
TI  - A Simple Test of Renal Efficiency.

PMID- 29647071
TI  - Clinical Meeting.

PMID- 29647072
TI  - A Neanderthaloid Skull Presenting Features of Cleidocranial Dysostosis and Other
      Peculiarities.

PMID- 29647073
TI  - The Use and Misuse of Carbohydrates.

PMID- 29647074
TI  - Avulsion of the Radial Attachment of the Biceps Brachii.

PMID- 29647075
TI  - Intracranial Aneurysms: Cerebral Arterio-Radiography: Surgical Treatment.

PMID- 29647077
TI  - Blood Serum and Callus.

PMID- 29647076
TI  - Chronic Nephrosis.

PMID- 29647078
TI  - Notes.

PMID- 29647079
TI  - Bee-Sting Treatment of Sciatica.

PMID- 29647080
TI  - Does Pregnancy Hasten the Fatal Termination in Rheumatic Heart Disease.

PMID- 29647081
TI  - Toxic Goitre: An Analysis of the Results of Surgical Treatment.

PMID- 29647082
TI  - Typhoid in a Rural Area: An Epidemiological Note.

PMID- 29647083
TI  - The Etiology of Recurrent Ocular Paralysis.

PMID- 29647084
TI  - The New OEstrogens.

PMID- 29647085
TI  - Modern Anaesthesia.

PMID- 29647086
TI  - Studies in Method and Standardisation of Blood Examination.-VII. Blood
      Sedimentation Rate, Sedimentation Volume and Centrifuge Volume.

PMID- 29647088
TI  - Notes.

PMID- 29647087
TI  - Studies on Stored Blood.: V. Observations on the Coagulation Mechanism in Stored
      Blood.

PMID- 29647089
TI  - Specialism.

PMID- 29647090
TI  - A Hundred Years Ago.-Orthopaedics.

PMID- 29647091
TI  - Studies on Stored Blood: VI.-Changes in the Erythrocytes during Storage.

PMID- 29647092
TI  - The Physiological Approach to Medical Problems.

PMID- 29647093
TI  - Nutritional Factors in Dark Adaptation.

PMID- 29647094
TI  - The Lighter Side of Edinburgh Medical Life at the End of the Nineteenth Century.

PMID- 29647095
TI  - Inspection.

PMID- 29647096
TI  - A Rare Medical Anomaly.

PMID- 29647097
TI  - Circulatory Collapse and Wound Shock.

PMID- 29647098
TI  - A Student of 1765-70-A Glimpse of Eighteenth-Century Medicine.

PMID- 29647099
TI  - Observations on the Classification of the Gliomas.

PMID- 29647100
TI  - Studies on Stored Blood: VII.-The Effect of Sodium Sulphapyridine, Albucid
      Soluble and Hydrogen Ion Concentration on Phagocytosis.

PMID- 29647101
TI  - The Treatment of Septicaemia.

PMID- 29647102
TI  - A Report on Six Obsessional Cases.

PMID- 29647103
TI  - Tobacco and Coronary Disease.

PMID- 29647104
TI  - Detecting Pelvic Contractions.

PMID- 29647105
TI  - Notes.

PMID- 29647106
TI  - "Night Cramps" Relieved by Quinine.

PMID- 29647107
TI  - Immunisation against Scarlet Fever by Oral Administration of Toxin.

PMID- 29647108
TI  - Sudden Blindness Following Gastro-Intestinal Haemorrhage.

PMID- 29647109
TI  - Orthopaedics: A Brief Survey of Its Position.

PMID- 29647110
TI  - Our Daily Bread.

PMID- 29647111
TI  - Cullen's Introduction to His Course of Clinical Lectures in the Spring of 1768.

PMID- 29647112
TI  - Notes.

PMID- 29647113
TI  - The Use of Sulfanilamide in Dermatology.

PMID- 29647114
TI  - War and Skin Disease.

PMID- 29647115
TI  - The Modern Methods of Treating Lung Tuberculosis.

PMID- 29647116
TI  - Cosmetic Irritants.

PMID- 29647117
TI  - The Cause and Treatment of the Lethal Factors in Burns.

PMID- 29647118
TI  - The Spread of Tuberculous Infection in the Child, and Its Relation to Disease in
      the Adult.

PMID- 29647119
TI  - Immunisation against Diphtheria.

PMID- 29647121
TI  - The Action of Drugs on the Human Uterus.

PMID- 29647120
TI  - The Use of Oxalated Finger Blood for Routine Haematological Examination.

PMID- 29647122
TI  - The Production of Glomerulo-Nephritis in Animals by the Injection of Serum from
      Patients Suffering from Nephritis.

PMID- 29647123
TI  - The Lighter Side of Edinburgh Medical Life at the End of the Nineteenth Century.

PMID- 29647125
TI  - Air-Raid Casualties.

PMID- 29647124
TI  - A Note on the Use of M & B 693 in the Pneumonia of Children.

PMID- 29647126
TI  - Some Comments on the Present State of Cancer Theory.

PMID- 29647127
TI  - Alleged Immunity from Danger of Sulphuric Ether in Anaesthesia.

PMID- 29647128
TI  - Medical Jurisprudence.

PMID- 29647129
TI  - Medical News.

PMID- 29647130
TI  - Royal College of Physicians, London.

PMID- 29647131
TI  - On the Treatment of Fracture of the Lower Extremity of the Radius.

PMID- 29647132
TI  - Varieties.

PMID- 29647133
TI  - On an Epidemic of Typhus in the North-West Provinces of India.

PMID- 29647135
TI  - Midwifery.

PMID- 29647134
TI  - Harveian Oration: Delivered by Dr Charles Bell, Annual President of the Harveian
      Society, on the 12th of April 1861.

PMID- 29647136
TI  - University of Edinburgh.

PMID- 29647137
TI  - Proceedings of the Edinburgh Obstetrical Society.

PMID- 29647138
TI  - Statistics of Prisoners: Their Mental Condition and Diseases.

PMID- 29647139
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29647141
TI  - A Short Account of Two Fatal Cases of Heat Apoplexy, Which Occurred in August
      Last on Board the Peninsular and Oriental Company's Screw-Steamer "Colombo," on
      Her Voyage from Suez to Aden.

PMID- 29647140
TI  - On Irregularities of the Omo-Hyoid Muscle; with Remarks upon Their Bearings on
      the Surgical Anatomy of the Muscle.

PMID- 29647142
TI  - On the Use of Alcoholic Stimulants in Hospital Medical Practice; with
      Illustrations from the Records of the Royal Infirmary of Edinburgh.

PMID- 29647143
TI  - Royal College of Surgeons Conversazione.

PMID- 29647144
TI  - Surgery.

PMID- 29647145
TI  - The Scientific Place and Principles of Medical Psychology: An Introductory
      Address.

PMID- 29647146
TI  - Royal College of Physicians of Edinburgh.

PMID- 29647147
TI  - On Partial and Complete Loss of Sight in Diabetes; with a Notice of Two Cases of
      Diabetic Cataract.

PMID- 29647148
TI  - Examination Paper-Scientific Department.

PMID- 29647149
TI  - Report of General Board of Lunacy for Scotland.

PMID- 29647150
TI  - Case of Pulsating Tumour in the Orbit, under the Care of Professor Syme, Cured by
      Ligature of the Common Carotid Artery; with Remarks.

PMID- 29647151
TI  - Court of Queen's Bench.

PMID- 29647152
TI  - The Attorney-General versus the Royal College of Physicians.

PMID- 29647153
TI  - Case of Pericoecal Abscess Simulating Strangulated Inguinal Hernia.

PMID- 29647155
TI  - Materia Medica.

PMID- 29647154
TI  - Preliminary Examination Papers for the Double Qualification Conferred by the
      Royal Colleges of Physicians and Surgeons of Edinburgh.

PMID- 29647156
TI  - The Diseases and Causes of Death Amongst the Poor of the Parish of St Mary-Le
      Bone, from 1839 to 1847.

PMID- 29647158
TI  - Medicine.

PMID- 29647157
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29647159
TI  - Quarterly Return of Births, Deaths, and Marriages in Scotland.

PMID- 29647160
TI  - Proceedings of the Edinburgh Obstetrical Society.

PMID- 29647161
TI  - Medicine.

PMID- 29647162
TI  - On Separation and Transplantation of the Ovary, Due to Atrophy of the Broad
      Ligament and Fallopian Tube; and on the Spontaneous Separation of Sub-Peritoneal
      Fibrous Tumours of the Uterus.

PMID- 29647164
TI  - The Association of Scottish Medical Practitioners.

PMID- 29647163
TI  - Case of Amputation at the Middle of the Thigh for Spreading Gangrene after
      Compound Fracture of the Leg, in Which Acupressure Was Employed to Secure the
      Arteries.

PMID- 29647165
TI  - On the Waxy or Amyloid Form of Bright's Disease.

PMID- 29647167
TI  - Surgery.

PMID- 29647166
TI  - Clinical History of Three Cases of Placenta Proevia, in Which Podalic Version Was
      Performed.

PMID- 29647168
TI  - Therapeutics.

PMID- 29647169
TI  - King's and Queen's College of Physicians in Ireland and the Degree of M.D.

PMID- 29647170
TI  - King and Queen's College of Physicians in Ireland.

PMID- 29647172
TI  - Scottish Universities Commission.

PMID- 29647171
TI  - On the Influence of Change of Posture on the Characters of Endocardial Murmurs;
      with an Attempt to Explain the Cause.

PMID- 29647174
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29647173
TI  - Midwifery.

PMID- 29647175
TI  - Royal College of Physicians of London.

PMID- 29647177
TI  - Election of Office-Bearers.

PMID- 29647176
TI  - Midwifery.

PMID- 29647178
TI  - Medicine.

PMID- 29647179
TI  - Report of Clinical Cases Treated during the Session 1859-60, in the Surgical
      Wards of the Royal Infirmary.

PMID- 29647180
TI  - Quarterly Report on Physiology.

PMID- 29647181
TI  - Letters from Vienna.-No. II.

PMID- 29647182
TI  - Clinical Report on the Diseases of Women; with Observations.

PMID- 29647183
TI  - Varieties.

PMID- 29647184
TI  - Quarterly Report of Cases Occurring at the Edinburgh Eye Infirmary, 140, George
      Street.

PMID- 29647185
TI  - On Pericarditis.

PMID- 29647186
TI  - Description of Two Cases of Exomphalos, with Observations on Foetal
      Malformations.

PMID- 29647188
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29647187
TI  - Royal College of Physicians.

PMID- 29647189
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29647191
TI  - Royal College of Surgeons-Conversazione.

PMID- 29647190
TI  - The Legal Relations of Insanity.

PMID- 29647193
TI  - Variety.

PMID- 29647192
TI  - Case of Puerperal Epileptic Convulsions.

PMID- 29647194
TI  - Medicine.

PMID- 29647196
TI  - On the Mode of Elimination of the Metal Manganese When Employed Medicinally.

PMID- 29647195
TI  - On the Radical Cure of Reducible Hernia.

PMID- 29647197
TI  - Quarterly Report of Cases Occurring at the Edinburgh Eye Infirmary, 140, George
      Street.

PMID- 29647198
TI  - The Imperial Academy of Medicine.

PMID- 29647199
TI  - A Case of Encephalocele; with the Theory of Its Growth.

PMID- 29647200
TI  - Quarterly Report on Physiology.

PMID- 29647202
TI  - Letters from Vienna.-No. III.

PMID- 29647201
TI  - Case of Fatal Croup in the Adult; with Remarks.

PMID- 29647203
TI  - Varieties.

PMID- 29647204
TI  - King's and Queen's College of Physicians in Ireland, and the Degree of M.D.

PMID- 29647205
TI  - Trial of John M'Fadyen for Murder at the Glasgow Winter Circuit, December 1860.

PMID- 29647206
TI  - Royal College of Surgeons' Conversazione.

PMID- 29647207
TI  - Medicine.

PMID- 29647208
TI  - Proceedings of the Edinburgh Obstetrical Society.

PMID- 29647209
TI  - Medical Examination Papers of the University of St Andrews-December, 1860.

PMID- 29647210
TI  - On the Rate of Mortality in the Medical Department of the British Navy for the
      Nine Years Ending in 1860.

PMID- 29647211
TI  - Quarterly Return of the Births, Deaths, and Marriages Registered in Scotland, for
      the Quarter Ending 31st December 1860.

PMID- 29647212
TI  - Notes upon Tracheotomy, with Cases; to Which Are Added Two Cases of Hernia.

PMID- 29647213
TI  - Case of Perforation of the Stomach Occurring under Unusual Circumstances.

PMID- 29647214
TI  - Testimonial to Professor Day.

PMID- 29647215
TI  - Scottish Universities Commission.

PMID- 29647216
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29647217
TI  - Presentation and Dinner to Dr Alexander Wood.

PMID- 29647218
TI  - Therapeutics.

PMID- 29647219
TI  - A Case in Which Two Ounces of the Wine of the Seeds of Colchicum Were
      Accidentally Taken, and Which Relieved a Gouty Diathesis.

PMID- 29647220
TI  - Two Cases of Tumour at the Base of the Brain, with Remarkably Contrasted
      Symptoms.

PMID- 29647221
TI  - Report of the Royal Maternity and Simpson Memorial Hospital for the Quarter
      Ending 31st October 1880.

PMID- 29647223
TI  - Monthly Retrospect of Obstetrics and Gynaecology.

PMID- 29647222
TI  - Case of Elephantiasis of Scrotum.

PMID- 29647224
TI  - Accumulations of Ceruminous and Sebaceous Secretions and Epidermis, and Foreign
      Bodies, in the External Auditory Meatus.

PMID- 29647225
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29647227
TI  - Medical News.

PMID- 29647226
TI  - The Influence of Antiseptics upon Legal Medicine: A Lecture Delivered in the
      Course of Clinical Surgery in the Munich Hospital, in the Winter Session 1879-80.

PMID- 29647228
TI  - Clinical Lectures on Intra-Cranial Tumours.

PMID- 29647229
TI  - Case of Splanchnic Inversion in an Athletic Young Man Aged Nineteen: With Remarks
      on the Cause and the Diagnosis of Congenital Transposition of Viscera.

PMID- 29647231
TI  - Heart Starvation.

PMID- 29647230
TI  - Meetings of Societies.

PMID- 29647232
TI  - Periscope of Otology.

PMID- 29647233
TI  - Part of a Clinical Lecture on the Operations from 1st November 1880 to 31st March
      1881 in Mr Joseph Bell's Wards.

PMID- 29647235
TI  - Monthly Retrospect of Obstetrics and Gynaecology.

PMID- 29647234
TI  - Occasional Periscope of Dermatology.

PMID- 29647236
TI  - Location and Administration of Special and General Hospitals in Which Contagious
      Diseases Are Received.

PMID- 29647237
TI  - Meetings of Societies.

PMID- 29647239
TI  - Medical News.

PMID- 29647238
TI  - Notes of a Case of Locomotor Ataxy, with Post-Mortem Examination.

PMID- 29647240
TI  - Occasional Periscope of Dermatology.

PMID- 29647242
TI  - On the Contagious Diseases Acts.

PMID- 29647241
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29647243
TI  - A Case of Malignant Disease (Sarcoma) of the Lung.

PMID- 29647244
TI  - Auditory Vertigo.

PMID- 29647245
TI  - On the Average Length and Weight of Mature New-Born Scotch Children.

PMID- 29647246
TI  - On Paralysis of Hands and Feet from Disease of Nerves.

PMID- 29647247
TI  - On a Form of Post-Partum Incontinence of Urine, and Its Treatment by Faradaism.

PMID- 29647248
TI  - On the Anatomical Relations of the Trachea in the Child.

PMID- 29647249
TI  - Observations on Ear Disease.

PMID- 29647250
TI  - Rejoinder to Dr Garson's Letter to the Editor Regarding the Review of Dr Fancourt
      Barnes' Translation of Martin's Atlas.

PMID- 29647251
TI  - Meetings of Societies.

PMID- 29647252
TI  - Correspondence.

PMID- 29647253
TI  - Some Account of a Very Severe Case of Membranous Dysmenorrhoea Treated by Rest,
      Chapman's Spinal Hot Bag, and Donovan's Solution.

PMID- 29647254
TI  - Lecture on Cyanosis.

PMID- 29647255
TI  - Case of Splanchnic Inversion in an Athletic Young Man Aged Nineteen: With Remarks
      on the Cause and the Diagnosis of Congenital Transposition of Viscera.

PMID- 29647256
TI  - Monthly Retrospect of Obstetrics and Gynaecology.

PMID- 29647257
TI  - Report of a Case of Hydatid Disease of the Liver Successfully Treated by
      Paracentesis.

PMID- 29647258
TI  - Correspondence.

PMID- 29647259
TI  - Meetings of Societies.

PMID- 29647260
TI  - Case of Vesico-Vaginal Fistula and Loss of Uterus.

PMID- 29647262
TI  - Lecture on Cyanosis.

PMID- 29647263
TI  - On Fever in Ningpo and Chefoo.

PMID- 29647261
TI  - Meningocele.

PMID- 29647264
TI  - Upon Paroxysmal Angina Pectoris and Other Forms of Cardiac Pain, with Some
      Remarks on the Diagnosis of Fatty Heart.

PMID- 29647266
TI  - Clinical Lectures on Intra-Cranial Tumours.

PMID- 29647265
TI  - On the Shape of the Empty Female Bladder.

PMID- 29647267
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29647268
TI  - Is Peat-Reek an Antidote to Phthisis?

PMID- 29647270
TI  - Periscope of Ophthalmology.

PMID- 29647269
TI  - A Statistical Inquiry into the Action of the Bromides in Epilepsy.

PMID- 29647271
TI  - Meetings of Societies.

PMID- 29647272
TI  - Large Calcareous Tumour, Involving Chiefly the Inner and Middle Portions of the
      Left Temporo-Sphenoidal Lobe, and Pressing upon the Left Crus and Optic Thalamus.

PMID- 29647273
TI  - A Method of Treatment for Certain Kinds of Incontinence of Urine in Women.

PMID- 29647274
TI  - On the Rate of Mortality in the Medical Department of the British Navy for the
      Ten Years Ending in December 1880.

PMID- 29647275
TI  - Periscope of Otology.

PMID- 29647276
TI  - Indications and Counter-Indications of Davos (Switzerland), with Some Statistics.

PMID- 29647277
TI  - Case of Coin in Air-Passages Treated by Inversion of the Patient.

PMID- 29647278
TI  - Quarterly Report of the Royal Maternity and Simpson Memorial Hospital.

PMID- 29647279
TI  - On a Complication of Occipito-Posterior Positions of the Vertex.

PMID- 29647280
TI  - On Some of the Phenomena of Parturition in Their Practical Aspects.

PMID- 29647282
TI  - The Dangers of Chronic Suppuration of the Middle Ear, and Their Prevention.

PMID- 29647281
TI  - On a Case of Hydrochloric Acid Poisoning, and Some Points in Practical
      Therapeutics.

PMID- 29647283
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29647285
TI  - Monthly Retrospect of Obstetrics and Gynaecology.

PMID- 29647284
TI  - Occasional Periscope of Dermatology.

PMID- 29647286
TI  - Medical News.

PMID- 29647287
TI  - The Influence of Antiseptics upon Legal Medicine : A Lecture Delivered in the
      Course of Clinical Surgery in the Munich Hospital, in the Winter Session 1879-80.

PMID- 29647289
TI  - The Axis-Traction Forceps.

PMID- 29647288
TI  - Case of Traumatic Facial Paralysis.

PMID- 29647290
TI  - Meetings of Societies.

PMID- 29647291
TI  - Occasional Periscope of Dermatology.

PMID- 29647292
TI  - On the Antiseptic Removal of Scrotal Elephantiasis.

PMID- 29647293
TI  - Case of Large Congenital Cystic Tumour of the Left Side of the Neck, Simulating
      Encephalocele: Death after the Third Month, from Suppuration of Its Contents and
      Meningitis.

PMID- 29647294
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29647295
TI  - The Systematic Use of Antiseptics in Midwifery Practice.

PMID- 29647296
TI  - A Statistical Inquiry into the Action of the Bromides in Epilepsy.

PMID- 29647297
TI  - Periscope of Otology.

PMID- 29647298
TI  - Clinical Lectures on Intra-Cranial Tumours.

PMID- 29647299
TI  - Note on a New Form of Rheophore and Galvanic Battery for Medical Use.

PMID- 29647300
TI  - Periscope of Ophthalmology.

PMID- 29647301
TI  - Medical News.

PMID- 29647302
TI  - Method of Case-Taking in Midwifery.

PMID- 29647303
TI  - A Case of Malignant Disease (Sarcoma) of the Lung.

PMID- 29647304
TI  - Clinical Retrospect of Cases Treated during the Session 1855-6 (November to
      March); Including Remarks upon the More Important Fatal Cases, and upon the Cases
      of Inflammation of the Lungs Treated during That Period.

PMID- 29647305
TI  - College of Surgeons-Third Conversazione.

PMID- 29647307
TI  - Letter from Professor Bennett.

PMID- 29647306
TI  - On a Peculiar Form of Sclerotitis.

PMID- 29647308
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29647309
TI  - On the Efficacy of Small Doses of Morphia (as Opposed to the Use of
      Expectorants), in the Treatment of Hooping-Cough, Chronic Bronchitis, and
      Phthisis.

PMID- 29647310
TI  - Case of Temporary Paralysis.

PMID- 29647311
TI  - Notes on the Surgery of the War.

PMID- 29647312
TI  - Harveian Society-Annual Festival.

PMID- 29647313
TI  - The New Registration Act.

PMID- 29647314
TI  - Varieties.

PMID- 29647315
TI  - Case of Sudden Death after Amputation of Leg, under the Influence of Chloroform.

PMID- 29647316
TI  - The Month.

PMID- 29647318
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29647317
TI  - Case of Poisoning by Eating American Partridge.

PMID- 29647319
TI  - Medicine.

PMID- 29647320
TI  - Case of Induction of Premature Labour.

PMID- 29647321
TI  - Surgery of the Crimean War.

PMID- 29647322
TI  - Cases of Gun-Shot Wounds.

PMID- 29647323
TI  - Experimental Notes on Glycerine.

PMID- 29647325
TI  - The Month.

PMID- 29647324
TI  - On a Hitherto Undescribed Disease of the Uterus, Namely, Unnatural Patency of the
      Inner Extremity of a Fallopian Tube.

PMID- 29647326
TI  - Obstetrical Society of Edinburgh.

PMID- 29647327
TI  - Note on the Occurrence of Paralysis and Muscular Atrophy in the Horse, in
      Connection with Arterial Obstruction and Obliteration.

PMID- 29647328
TI  - Singular Case of Apparent Intra-Uterine Disease.

PMID- 29647329
TI  - Cases of Erysipelas and Phlegmasia Dolens.

PMID- 29647330
TI  - Surgery.

PMID- 29647331
TI  - Varieties.

PMID- 29647332
TI  - Treatment of Surgeons on Board Whaling-Vessels.

PMID- 29647333
TI  - Observations on Croup: Special Diagnosis.

PMID- 29647334
TI  - Observations on Primary Amputation, with Cases.

PMID- 29647335
TI  - Edinburgh Chair of Practice of Physic.

PMID- 29647336
TI  - Histology of the Cholera Evacuations in Man and the Lower Animals.

PMID- 29647337
TI  - Account of a Late Remarkable Trial for Poisoning with Arsenic.

PMID- 29647338
TI  - Varieties.

PMID- 29647339
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29647340
TI  - Edinburgh Obstetrical Society.

PMID- 29647341
TI  - The Month.

PMID- 29647343
TI  - On the Nervous Element in Inflammation, and Its Influence on Treatment.

PMID- 29647342
TI  - Case of Chronic Hydrocephalus Connected with Cancer at the Base of Brain.

PMID- 29647345
TI  - The Month.

PMID- 29647344
TI  - A Few Remarks on Dilution as a Principle in Therapeutics.

PMID- 29647346
TI  - A Complicated Case of Hernia.

PMID- 29647347
TI  - On the Mode of Communication of Cholera.

PMID- 29647348
TI  - Therapeutical Record.

PMID- 29647349
TI  - Case of Hoemorrhagic Diathesis, in Which the Bleeding from the Gum Was Arrested
      Only by the Extraction of the Tooth in Its Immediate Vicinity.

PMID- 29647350
TI  - Case of Tobacco Poisoning in a Maniac.

PMID- 29647351
TI  - Practical Remarks on the Physical Diagnosis of Phthisis Pulmonalis.

PMID- 29647352
TI  - Account of a Late Remarkable Trial for Poisoning with Arsenic.

PMID- 29647353
TI  - On the Use of Potassio-Tartrate of Antimony, in the Form of Enema, in Obstetric
      Practice.

PMID- 29647354
TI  - On the Diagnostic Value of Albumen in the Urine.

PMID- 29647355
TI  - Varieties.

PMID- 29647356
TI  - Medicine.

PMID- 29647357
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29647358
TI  - Case of Sudden Death from Fatty Degeneration of the Heart.

PMID- 29647359
TI  - Case of Capillary Bronchitis and Extensive Inflammation of the Intestinal Mucous
      Membrane.

PMID- 29647360
TI  - Report by the Royal College of Surgeons of Edinburgh, on the Bill Brought into
      Parliament by Mr Headlam, "To Alter and Amend the Laws Regulating the Medical
      Profession."

PMID- 29647361
TI  - Case of Poisoning with Croton Oil.

PMID- 29647362
TI  - Observations on Croup: Differential Diagnosis.

PMID- 29647363
TI  - Account of the Bathing Seasons, 1854 and 1855.

PMID- 29647364
TI  - Varieties.

PMID- 29647365
TI  - Edinburgh Practice of Physic Chair.

PMID- 29647366
TI  - On the Lateral Movements of the Foot.

PMID- 29647367
TI  - The Month.

PMID- 29647368
TI  - Cases of Gun-Shot Wounds.

PMID- 29647369
TI  - Royal College of Surgeons-Second Conversazione.

PMID- 29647371
TI  - Royal Medical Society-Conversazione.

PMID- 29647370
TI  - Notes on the Formation of the Ricketty and Malacosteon Pelves, Chiefly after the
      Researches of M. Meyer of Zurich.

PMID- 29647372
TI  - Injuries of the Head and Face.

PMID- 29647373
TI  - Two Cases of Excision of the Knee Joint.

PMID- 29647374
TI  - Case of Tic Doloureux Cured by the Excision of a Mass of Phosphate of Lime,
      Adhering to the Supra-Orbital Nerve.

PMID- 29647375
TI  - Resolutions in Reference to Mr Headlam's Medical Bill, Adopted by the Royal
      College of Physicians of Edinburgh, at a Meeting Held on the 18th March 1856.

PMID- 29647376
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29647377
TI  - Conversazione of the Royal College of Surgeons.

PMID- 29647378
TI  - New Medical Bill.

PMID- 29647379
TI  - A Clinical Investigation into the Diagnostic Value of the Cracked Pot Sound
      (Bruit De Pot Fele of Laennec).

PMID- 29647380
TI  - Histology of the Cholera Evacuations in Man and the Lower Animals.

PMID- 29647381
TI  - Deviations from the Laws of Mortality.

PMID- 29647382
TI  - Reflections on the Results of Experience as to the Symptoms of Internal
      Inflammations, and the Effects of Bloodletting, during the Last Forty Years.

PMID- 29647384
TI  - Edinburgh Obstetrical Society.

PMID- 29647383
TI  - Medico-Legal Observations on Manual Strangulation and Death by External Violence,
      with Experiments and Illustrative Cases.

PMID- 29647385
TI  - The Edinburgh Frofessorship of Military Surgery.

PMID- 29647386
TI  - On the Impropriety of Applying the Term Leuchemia (White Blood) to Red Blood,
      Containing an Excess of Colourless Corpuscles.

PMID- 29647387
TI  - The Month.

PMID- 29647388
TI  - Projected Bibliography of Croup.

PMID- 29647390
TI  - Report of Cases Treated in the Edinburgh Eye-Infirmary during the Last Five
      Years.

PMID- 29647389
TI  - A Few Remarks on Cholera.

PMID- 29647391
TI  - Popliteal Aneurism, Unsuccessfully Treated by Pressure.

PMID- 29647392
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29647393
TI  - Isolation of the Bacillus Tuberculosis from Sputum : Comparison of the Antiformin
      and Sulphuric Acid Methods.

PMID- 29647394
TI  - Results of Recent Studies on Anterior Pituitary Hormones.

PMID- 29647395
TI  - Traumatic Meningeal Haemorrhage, with a Review of Seventy-One Cases.

PMID- 29647397
TI  - Editorial Note.

PMID- 29647396
TI  - Lister and His Contemporaries in Edinburgh.

PMID- 29647398
TI  - Harvey in Scotland.

PMID- 29647400
TI  - Can We "Breed out" Cancer in the Human Race?

PMID- 29647399
TI  - The Neuro-Psychiatric Aspects of Bromide Intoxication.

PMID- 29647401
TI  - The Treatment of Minor Foot Disabilities.

PMID- 29647402
TI  - Modern Developments in the Organisation of the Treatment of Fractures.

PMID- 29647403
TI  - The Significance of Cardiac Venous Congestion.

PMID- 29647404
TI  - Primary Toxic Goitre.

PMID- 29647405
TI  - William Osler.

PMID- 29647406
TI  - Right-Sided Aortic Arch.

PMID- 29647407
TI  - Pernicious Anaemia and Its Treatment.

PMID- 29647408
TI  - Experimental Neuroses in Animals and Their Treatment with Bromides.

PMID- 29647409
TI  - Notes.

PMID- 29647410
TI  - Biological Properties of Killed Tubercle Bacilli Deprived of Acid-Fastness by the
      Method of Browning and Gulbransen.

PMID- 29647411
TI  - Medical Education in Scotland.

PMID- 29647413
TI  - Occasional Periscope of Surgery and Surgical Pathology.

PMID- 29647412
TI  - Notes.

PMID- 29647415
TI  - List of Hospitals, Dispensaries, etc., in Connexion with the Medical Schools of
      Scotland.

PMID- 29647414
TI  - Report of the Ear Dispensary, 6 Cambridge Street, Lothian Road.

PMID- 29647416
TI  - The Pathology of Rickets.

PMID- 29647418
TI  - Navy Medical Department.

PMID- 29647417
TI  - Army Medical School.

PMID- 29647419
TI  - Preliminary Examinations for the Diplomas of the Royal Colleges of Physicians and
      Surgeons of Edinburgh, during the Year 1882-83.

PMID- 29647420
TI  - Puerperal Fever: Its Treatment and Prevention.

PMID- 29647421
TI  - Case of Extra-Uterine (Tubal) Pregnancy.

PMID- 29647422
TI  - Arguments in Favour of the Theory of Dilatation of the Heart as the Cause of
      Cardiac Haemic Murmurs, and of the Appendix of the Left Auricle Being the Primary
      Seat of This Murmur.

PMID- 29647423
TI  - Toilet Drunkenness.

PMID- 29647424
TI  - Periscope of Ophthalmology.

PMID- 29647425
TI  - Periscope of Syphilology.

PMID- 29647426
TI  - Occasional Periscope of Dermatology.

PMID- 29647427
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29647428
TI  - Soluble Hypodermic Tablets.

PMID- 29647429
TI  - Case of Extirpation of the Uterus through the Vagina for Carcinoma.

PMID- 29647430
TI  - Notes of Two Midwifery Cases.

PMID- 29647431
TI  - A Case of Poisoning by Hydrochloric Acid and Chloride of Zinc.

PMID- 29647432
TI  - Royal College of Surgeons, Edinburgh.

PMID- 29647433
TI  - The Cardiac Inorganic Murmurs in Debility and Anaemia: A Reply to Dr Balfour of
      Edinburgh.

PMID- 29647434
TI  - The Examination of Deaf-Mutes.

PMID- 29647435
TI  - Monthly Retrospect of Obstetrics and Gynaecology.

PMID- 29647436
TI  - "Horse Sense" in Diagnosis.

PMID- 29647438
TI  - Occasional Periscope of Surgery and Surgical Pathology.

PMID- 29647437
TI  - Periscope of Otology.

PMID- 29647439
TI  - Fifeshire Medical Association.

PMID- 29647440
TI  - Comparative Size of Drops.

PMID- 29647441
TI  - Mr Tait's Brilliant Results Welcomed in America.

PMID- 29647442
TI  - Four and a Half Years' Experience in the Lock Wards of the Edinburgh Royal
      Infirmary.

PMID- 29647443
TI  - Statistics of Operations in Mr Bell's Wards, Royal Infirmary, Edinburgh, during
      the Summer Session 1882.

PMID- 29647444
TI  - The Curious History of an Anatomical Specimen.

PMID- 29647446
TI  - Meetings of Societies.

PMID- 29647445
TI  - Occasional Periscope of Dermatology.

PMID- 29647447
TI  - New Parasites.

PMID- 29647448
TI  - Royal College of Physicians, Edinburgh.

PMID- 29647449
TI  - On Some Points in the Physics of the Bladder and Rectum: Specially in Relation to
      the Structural Anatomy of the Female Pelvic Floor.

PMID- 29647450
TI  - Periscope of Otology.

PMID- 29647452
TI  - A Case of Diabetic Coma with Lipaemia.

PMID- 29647451
TI  - The Medical Congress of Seville.

PMID- 29647453
TI  - Case of Large Congenital Cystic Tumour of the Back of the Head: Removal; Death on
      Ninth Day from Convulsions.

PMID- 29647454
TI  - The Diagnosis of Advanced Extra-Uterine Gestation after the Death of the Foetus
      (With a Frozen Section).

PMID- 29647455
TI  - Periscope of Syphilology.

PMID- 29647456
TI  - Note on the Position and Mechanism of the Haemic Murmur: In Reply to the Paper by
      Dr Russell of Carlisle.

PMID- 29647457
TI  - Royal Colleges of Physicians and Surgeons, Edinburgh.

PMID- 29647458
TI  - Quarterly Report of the Royal Maternity and Simpson Memorial Hospital.

PMID- 29647459
TI  - Election of Robert Barnes, M.D., F.R.C.P., as Honorary Consulting Physician to
      the Chelsea Hospital for Women.

PMID- 29647460
TI  - Occasional Periscope of Surgery and Surgical Pathology.

PMID- 29647461
TI  - Periscope of Ophthalmology.

PMID- 29647462
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29647463
TI  - Parturition Complicated with Whooping-Cough and Pleurisy: Recovery.

PMID- 29647464
TI  - Note of a Somewhat Unusual and Complicated Case of Inguinal Hernia.

PMID- 29647465
TI  - The Treatment of Diphtheritic Sore Throat.

PMID- 29647466
TI  - Periscope of State Medicine.

PMID- 29647467
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29647468
TI  - Meetings of Societies.

PMID- 29647469
TI  - Medical Bravery.

PMID- 29647470
TI  - The Late Professors Bennett and Goodsir.

PMID- 29647471
TI  - Shearing or Moulding of the Foetal Head, in Its Medico-Legal Aspects.

PMID- 29647472
TI  - A Case of Brain Tumour.

PMID- 29647473
TI  - Occasional Periscope of Dermatology.

PMID- 29647474
TI  - History of the Chair of Midwifery and the Diseases of Women and Children in the
      University of Edinburgh: An Introductory Lecture.

PMID- 29647475
TI  - Grant College Medical Society.

PMID- 29647476
TI  - A New Disease.

PMID- 29647477
TI  - Royal Colleges of Physicians and Surgeons, Edinburgh.

PMID- 29647479
TI  - University of Edinburgh.

PMID- 29647478
TI  - Periscope of Otology.

PMID- 29647480
TI  - Dr Holmes on Physical Diagnosis and Specialism.

PMID- 29647481
TI  - Monthly Retrospect of Obstetrics and Gynaecology.

PMID- 29647482
TI  - The Examination of Deaf-Mutes.

PMID- 29647483
TI  - Surgery past and Present: Being an Introductory Lecture Delivered at the
      Commencement of the Session 1882-83 to the Class of Surgery at Minto House
      Medical School.

PMID- 29647485
TI  - Royal College of Physicians, Edinburgh.

PMID- 29647484
TI  - Occasional Periscope of Surgery and Surgical Pathology.

PMID- 29647486
TI  - Notes on the Recent Epidemic of Measles in Iceland.

PMID- 29647487
TI  - The Psychological Problem of Venereal Disease.

PMID- 29647489
TI  - The Lung and Pleura-Certain Anatomical Facts in Relation to Disease.

PMID- 29647488
TI  - Nasal Sinusitis and Mental Disorder. A Survey of 818 Cases.

PMID- 29647490
TI  - The Highlands and Islands Medical Service: What It Is, and What It Has Done.

PMID- 29647491
TI  - Benign Intrathoracic Tumours: With Notes on Two Cases.

PMID- 29647492
TI  - The Milk Supply.

PMID- 29647493
TI  - Medical Practice of the Future.

PMID- 29647494
TI  - Debatable Tumours in Human and Animal Pathology-III. Seminoma.

PMID- 29647495
TI  - Valedictory Address on "Impressions and Experiences of a Country Doctor in the
      'Nineties and after".

PMID- 29647496
TI  - Some Observations on the Notifiable Streptococcal Infections.

PMID- 29647497
TI  - Notes.

PMID- 29647498
TI  - Chronic Nutritional Hypochromic Anaemia.

PMID- 29647499
TI  - The Neuro-Psychological Basis of Conduct Disorder.

PMID- 29647500
TI  - Passages of Medical History-Edinburgh Medicine, 1800-1828.

PMID- 29647501
TI  - Notes.

PMID- 29647502
TI  - Disorders of the Interstitial Circulation.

PMID- 29647503
TI  - Chronic Nutritional Hypochromic Anaemia.

PMID- 29647504
TI  - The Neuro-Psychological Basis of Conduct Disorder.

PMID- 29647505
TI  - Queer Patients-Some Notes on Artefacts.

PMID- 29647507
TI  - Notes.

PMID- 29647506
TI  - Clinical Meeting.

PMID- 29647508
TI  - Diet and Dyspepsia.

PMID- 29647510
TI  - Observations on the Carbonic Anhydrase of the Blood in Anaemia and in Other
      Pathological Conditions.

PMID- 29647509
TI  - The Dietetic Treatment of the Average Diabetic.

PMID- 29647511
TI  - Thoughts and Afterthoughts about Specialists and Others.

PMID- 29647512
TI  - Notes.

PMID- 29647513
TI  - The Surgical Treatment of Cardiac Pain.

PMID- 29647514
TI  - Moscow: The Sklifasofsky Institute.

PMID- 29647515
TI  - Suicide.

PMID- 29647517
TI  - Modern Anaesthesia and the General Practitioner of To-Morrow.

PMID- 29647516
TI  - Debatable Tumours in Human and Animal Pathology-IV. "Mixed Tumours" of Salivary
      Glands.

PMID- 29647518
TI  - Preventive Medicine and Control and Treatment of Tuberculosis as Seen in Soviet
      Russia.

PMID- 29647519
TI  - Myocardial Infarction-A Pathological Study.

PMID- 29647520
TI  - The Importance of a Family History of Tuberculosis, with Special Reference to
      Life Assurance.

PMID- 29647521
TI  - Hilar Shadows and Gastric Lavage for the Isolation of Tubercle Bacilli.

PMID- 29647522
TI  - Surgery in General Practice.

PMID- 29647523
TI  - Upon the Pupil Reactions-With Special Reference to Contributions by Alumni of the
      Edinburgh School.

PMID- 29647524
TI  - Some Impressions of a Short Visit to Russia.

PMID- 29647525
TI  - Chronic Nutritional Hypochromic Anaemia.

PMID- 29647526
TI  - Russian Guides, Medical Schools and Research.

PMID- 29647527
TI  - Cysticercosis and Epilepsy.

PMID- 29647529
TI  - Structural Anomalies of the Forefoot in Relation to Some Metatarsal Disturbances.

PMID- 29647528
TI  - Chemotherapeutic Antiseptics.

PMID- 29647530
TI  - Debatable Tumours in Human and Animal Pathology-I. Lymphoepithelioma.

PMID- 29647531
TI  - Communism as an Anthropological Phenomenon.

PMID- 29647532
TI  - A Microscopical Inquiry into the AEtiology of Measles.

PMID- 29647533
TI  - Clinical Meeting.

PMID- 29647534
TI  - The Interpretation and Significance of Gordon's Test in the Diagnosis of
      Hodgkin's Disease. A Study of 100 Cases.

PMID- 29647536
TI  - Notes.

PMID- 29647535
TI  - Certain Types of Alimentary Neurosis.

PMID- 29647537
TI  - The Treatment of Acute Pleural Empyema.

PMID- 29647538
TI  - Observations on Pulmonary Tuberculosis in Children.

PMID- 29647539
TI  - Debatable Tumours.-II. Lymphosarcoma.

PMID- 29647540
TI  - The Study of the Face and of the Facial Expression of the Sick Child.

PMID- 29647541
TI  - Alcohol and the Motor-Driver.

PMID- 29647542
TI  - Some Besetments of Mid-Life.

PMID- 29647543
TI  - The Tryptophane Reaction as an Aid to the Early Diagnosis of Meningeal
      Tuberculosis.

PMID- 29647545
TI  - Seasonal Variation in Tuberculosis as Illustrated in a Study of Body Temperature
      and Body Weight.

PMID- 29647544
TI  - Clinical Meeting.

PMID- 29647546
TI  - A Survey of Volhard's Views on Hypertension and Haematogenous Bilateral Kidney
      Diseases.

PMID- 29647547
TI  - Harvey and the Human Heart.

PMID- 29647549
TI  - Notes.

PMID- 29647548
TI  - Diagnosis.

PMID- 29647550
TI  - Pulmonary Tuberculosis in Children.

PMID- 29647552
TI  - The Treatment of Pneumonia with Intravenous Injections of Iodine.

PMID- 29647551
TI  - Medical Education in Scotland.

PMID- 29647553
TI  - The Swedish System of State Medicine.

PMID- 29647554
TI  - Primary Thrombosis of the Axillary Vein.

PMID- 29647555
TI  - Recurring Arthritis of the Hip Associated with Acetonaemia.

PMID- 29647556
TI  - Threatened Gangrene. A Study of a Case Exhibiting the Signs and Symptoms of
      Obstructive Disease of the Peripheral Circulation.

PMID- 29647557
TI  - Rest in Bed.

PMID- 29647559
TI  - The Outlook on Cancer.

PMID- 29647558
TI  - Carcinoma of the Stomach.

PMID- 29647560
TI  - Abdominal Surgery in Infancy and Childhood.

PMID- 29647562
TI  - Notes.

PMID- 29647561
TI  - Observations on, and Methods of Treatment of, Tuberculosis of Kidney.

PMID- 29647563
TI  - Hypertension Associated with Experimental Serum Nephritis.

PMID- 29647564
TI  - Types of Tubercle Bacilli in 100 Cases of Non-Pulmonary Tuberculosis.

PMID- 29647565
TI  - A Tuberculin Survey of Children in the West of Scotland.

PMID- 29647566
TI  - Some Observations on the Treatment of Lupus.

PMID- 29647567
TI  - The Erythrogenic Toxins of Haemolytic Streptococci.

PMID- 29647568
TI  - Collapse Therapy: General Results and Their Implications.

PMID- 29647569
TI  - Studies in Method and Standardisation of Blood Examination-V. The Blood Platelet
      Count.

PMID- 29647570
TI  - Excretory Bacilluria.

PMID- 29647571
TI  - Notes.

PMID- 29647572
TI  - Experiments in Intestinal Obstruction: The Role Played by the Diminution of the
      Effective Circulating Blood Volume in Acute Intestinal Obstruction.

PMID- 29647573
TI  - A Study of the Contractions of the Non-Pregnant Human Uterus.

PMID- 29647574
TI  - The Doctor and the Public Happiness.

PMID- 29647575
TI  - Studies in Method and Standardisation of Blood Examination: III.
      Haemoglobinometry by a Whole-Blood Method.

PMID- 29647576
TI  - Discussion on the Report of the Departmental Committee on Scottish Health
      Services.

PMID- 29647577
TI  - Sarcomatosis in Fowls Following Weasel Bites: With a Discussion on Tumour
      Formation in General.

PMID- 29647579
TI  - The Conservative Treatment of Acute Infections.

PMID- 29647578
TI  - Studies on Carbohydrate Metabolism in Nervous and Mental Disorders-II. A
      Comparison of the Hyperglycaemic Index and Choline Esterase Activity in Anxiety
      and Depressive States.

PMID- 29647580
TI  - A Voice from the Grandstand.

PMID- 29647581
TI  - Certain Problems of Urinary Infection in Practice.

PMID- 29647582
TI  - Results of Treatment of Tabes Dorsalis.

PMID- 29647583
TI  - Fungus Infection of the Hands and Feet.

PMID- 29647584
TI  - Studies on Carbohydrate Metabolism in Nervous and Mental Disorders. III. The
      Disturbance of the Glucose Tolerance Test Caused by Hypnotics in Clinical Doses.

PMID- 29647585
TI  - Notes.

PMID- 29647586
TI  - The Technique of Tissue Culture.

PMID- 29647587
TI  - The Basophil Cell of the Hypophysis Cerebri: Stages in Its Life-History.

PMID- 29647588
TI  - Clinical Meeting.

PMID- 29647590
TI  - Achlorhydria: Or "A Sea of Troubles".

PMID- 29647589
TI  - Studies in Method and Standardisation of Blood Examination-IV. Estimation of
      Erythrocyte Fragility and a Normal Standard.

PMID- 29647591
TI  - Virus Bodies: John Buist and the Elementary Bodies of Vaccinia.

PMID- 29647593
TI  - Notes.

PMID- 29647592
TI  - The Laevulose Tolerance Test of Hepatic Insufficiency.

PMID- 29647594
TI  - The Royal Infirmary of Edinburgh: The New Orthopaedic Department.

PMID- 29647595
TI  - John Brown Buist, M.D. (Edin.), B.Sc. (Edin.), F.R.C.P.Ed., F.R.S.Ed. (1846
      1915): An Acknowledgment of His Early Contributions to the Bacteriology of
      Variola and Vaccinia.

PMID- 29647596
TI  - The Treatment of Fractured Bones by Internal Traction.

PMID- 29647598
TI  - Tuberculin Testing of Cattle-Methods and Interpretation.

PMID- 29647597
TI  - Acute Otitis Media and Mastoiditis: The Indications for Operation.

PMID- 29647599
TI  - Implantation of the Ovum in Mammals in the Light of Recent Research.

PMID- 29647600
TI  - The Edinburgh Tuberculosis Scheme, 1887-1937.

PMID- 29647601
TI  - Tuberculosis in Cattle, with Special Reference to Congenital Tuberculosis in
      Calves.

PMID- 29647602
TI  - The Intraspinal Injection of Alcohol for the Relief of Intractable Pain.

PMID- 29647603
TI  - Diabetes and Tuberculosis.

PMID- 29647604
TI  - Passages of Medical History. Edinburgh Medicine, 1750-1800.

PMID- 29647605
TI  - Clinical Notes on Eight Cases of Lymphogranuloma Inguinale (Climatic Bubo) and
      Its Sequelae.

PMID- 29647606
TI  - Notes.

PMID- 29647607
TI  - Vomiting in Infancy.

PMID- 29647608
TI  - Malignant Disease of the Thyroid: Observations on a Series of Twenty Cases, with
      Special Reference to Results of Treatment.

PMID- 29647609
TI  - General Prognostic Aspects of Tuberculous Adenitis of the Abdomen.

PMID- 29647610
TI  - The Value of the Examination of Contacts in Pulmonary Tuberculosis.

PMID- 29647611
TI  - Radiological Aspects of Tuberculous Adenitis of the Abdomen.

PMID- 29647612
TI  - The Bacteriology of Tuberculous Abdominal Adenitis.

PMID- 29647613
TI  - The Pharmacology of Some Newer Drugs Employed in Tuberculosis Therapy.

PMID- 29647614
TI  - Surgical Aspects of Tuberculous Adenitis of the Abdomen.

PMID- 29647615
TI  - Demonstrations.

PMID- 29647616
TI  - Some Biochemical Factors of Influenza and Other Viruses.

PMID- 29647617
TI  - Medical Education and Hospital Policy in Edinburgh.

PMID- 29647618
TI  - Intracranial Tuberculoma.

PMID- 29647619
TI  - Cancer.

PMID- 29647620
TI  - Discussion on Hospital Service.

PMID- 29647621
TI  - Notes.

PMID- 29647622
TI  - Surgery of Malignant Disease of the Colon.

PMID- 29647623
TI  - Some Observations on the Practice of Medicine.

PMID- 29647624
TI  - Haemorrhage in Jaundice.

PMID- 29647625
TI  - Observations on the Virus of Influenza, with a View to Elaborating a Simple
      Diagnostic Test Whereby Its Presence in the Respiratory Tract of Man May Be
      Revealed-Part II.

PMID- 29647626
TI  - Notes.

PMID- 29647627
TI  - Epidemiological Aspects of Pulmonary Tuberculosis Due to Bovine Type Tubercle
      Bacilli.

PMID- 29647628
TI  - Alveolar and Broncho-Pneumonia in Childhood.

PMID- 29647630
TI  - Giant-Cell Tumour of Bone.

PMID- 29647631
TI  - Notes on the Physiology and Pathology of Voice.

PMID- 29647629
TI  - Further Studies on Van Den Bergh's Test.

PMID- 29647633
TI  - The Investigation and Treatment of Obstructive Peripheral Vascular Disease.

PMID- 29647632
TI  - Psychotherapy in General Practice.

PMID- 29647634
TI  - Observations on the Virus of Influenza, with a View to Elaborating a Simple
      Diagnostic Test Whereby Its Presence in the Respiratory Tract of Man May Be
      Revealed-Part IV.

PMID- 29647636
TI  - Carcinoma of the Head of the Pancreas: A Case Treated by Radical Operation.

PMID- 29647635
TI  - Hepatitis.

PMID- 29647637
TI  - Cyclopropane.

PMID- 29647638
TI  - The Significance of Glycosuria.

PMID- 29647639
TI  - In Search of Hearing.

PMID- 29647640
TI  - Notes.

PMID- 29647641
TI  - Protein in the Treatment of Nephritis.

PMID- 29647642
TI  - Uncommon Ovarian Tumours-A Short Description of the Granulosa Cell Tumour,
      Brenner's Tumour, Disgerminoma and Arrhenoblastoma.

PMID- 29647643
TI  - A Case of Hodgkin's Disease with Cutaneous and Cerebral Manifestations.

PMID- 29647644
TI  - Observations on the Virus of Influenza, with a View to Elaborating a Simple
      Diagnostic Test Whereby Its Presence in the Respiratory Tract of Man May Be
      Revealed-Part V.

PMID- 29647645
TI  - The Rational Use of Digitalis.

PMID- 29647646
TI  - Observations on the Virus of Influenza, with a View to Elaborating a Simple
      Diagnostic Test Whereby Its Presence in the Respiratory Tract of Man May Be
      Revealed-Part III.

PMID- 29647647
TI  - Neurology-Some Modern Problems.

PMID- 29647648
TI  - Addison's Disease. The Diagnostic Significance of the Sodium and Chlorine Content
      of the Blood and Urine.

PMID- 29647650
TI  - Clinical Meeting.

PMID- 29647649
TI  - Debatable Tumours in Human and Animal Pathology-VII. Granulosa-Cell Tumour of the
      Ovary.

PMID- 29647651
TI  - Notes.

PMID- 29647652
TI  - The Expectancy of Life after Ureteral Transplantation.

PMID- 29647653
TI  - Observations on the Virus of Influenza, with a View to Elaborating a Simple
      Diagnostic Test Whereby Its Presence in the Respiratory Tract of Man May Be
      Revealed-Part I.

PMID- 29647654
TI  - Tumours of the Lung, Mediastinum and Pleura.

PMID- 29647655
TI  - The Field of Vision and the Anatomy of the Visual Nerve Path.

PMID- 29647656
TI  - The Treatment of Naevus.

PMID- 29647657
TI  - Against the Pendulum Movement in Working the Midwifery Forceps.

PMID- 29647659
TI  - Meetings of Societies.

PMID- 29647658
TI  - Prostitution.

PMID- 29647660
TI  - On the External Uses of the Hydrate of Chloral.

PMID- 29647661
TI  - On the Practice of Medical Jurisprudence.-No. III. Post-Mortem Examination.

PMID- 29647662
TI  - On Inflammation. Chapter III.

PMID- 29647663
TI  - Closure of the Genital Fissure as a Means of Treatment in Cases of Vesico-Vaginal
      Fistula with Extensive Destruction of the Substance of the Bladder and of the
      Anterior Vaginal Wall.

PMID- 29647664
TI  - On the Pathology and Operative Treatment of Hip Disease.

PMID- 29647666
TI  - Lupus of the Mouth and Pharynx.

PMID- 29647667
TI  - A Vacation Homily.

PMID- 29647665
TI  - Case of Meniere's Disease.

PMID- 29647669
TI  - American Centennial Celebration.

PMID- 29647670
TI  - Do Medical Men Live Long?

PMID- 29647668
TI  - Sclerosis in Scattered Patches.

PMID- 29647671
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29647672
TI  - Fees for Medico-Legal Work.

PMID- 29647673
TI  - Election of Office-Bearers, Medico-Chirurgical Society of Edinburgh, Edinburgh
      Obstetrical Society, and Royal Medical Society of Edinburgh.

PMID- 29647674
TI  - Laceration of the Perineum.

PMID- 29647676
TI  - Influence of Weather on Mortality from Different Diseases and Different Ages.

PMID- 29647675
TI  - On Inflammation.

PMID- 29647677
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29647678
TI  - A. Hiller, Experimental Investigation Regarding the Organized Nature of Contagia
      and Putrefaction.

PMID- 29647679
TI  - A Ready Method of Preparing Sections of Diseased Tissues for the Microscope.

PMID- 29647680
TI  - Note on Jaborandi.

PMID- 29647682
TI  - J. Orth on Tuberculosis.

PMID- 29647681
TI  - Correspondence.

PMID- 29647683
TI  - On the Pathology and Operative Treatment of Hip Disease.

PMID- 29647684
TI  - Clinical Lecture on Intermittency and Irregularity of the Pulse, and on
      Palpitation, Cardiac and Aortic.

PMID- 29647685
TI  - Meetings of Societies.

PMID- 29647686
TI  - Sarcoma Uteri.

PMID- 29647687
TI  - Tumour of the Dura Mater.

PMID- 29647688
TI  - On Rheumatoid Arthritis: Its Diagnosis, Pathology, and Treatment.

PMID- 29647689
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29647690
TI  - Royal Edinburgh Asylum Papers. Disorders of Speech in Insanity.

PMID- 29647692
TI  - Morphia.

PMID- 29647691
TI  - Copaiba.

PMID- 29647694
TI  - Diphtheria: Typical Cases, in Illustration of Its Diagnosis, Prognosis, and
      Treatment; Together with Remarks on the Signification of Albuminuria in That
      Disease.

PMID- 29647693
TI  - Case of Absence of Uterus, with a Tumour of Doubtful Character in Each Inguinal
      Canal.

PMID- 29647695
TI  - Bromhydrate of Quinine.

PMID- 29647696
TI  - Picrotoxine.

PMID- 29647697
TI  - On Excision of Isolated Bones of the Tarsus, Preserving a Useful Foot.

PMID- 29647698
TI  - On the Reflex Functions of the Spinal Cord.

PMID- 29647699
TI  - Digitalis.

PMID- 29647700
TI  - Opium and Belladonna.

PMID- 29647701
TI  - Nursing in the Edinburgh Infirmary.

PMID- 29647702
TI  - On Inflammation. Chapter V.

PMID- 29647703
TI  - Meetings of Societies.

PMID- 29647704
TI  - On Rupture of the Perineum, and Especially on the Division of the Perineum and
      Rectovaginal Septum, by Post-Partum Sloughing.

PMID- 29647705
TI  - Pill for the Keighley Board of Guardians.

PMID- 29647707
TI  - Sclerosis in Scattered Patches.

PMID- 29647706
TI  - A Typhoid Epidemic Spread by Infected Milk: Allgem. Zeitshr. f. Epidemiol., 1875,
      S. 298.

PMID- 29647708
TI  - On the Complete Evacuation of the Uterus after Abortion.

PMID- 29647709
TI  - The Histological Changes Which Take Place in the Labyrinth from Certain
      Infectious Diseases.

PMID- 29647711
TI  - Unauthorized Visitors.

PMID- 29647710
TI  - On the Compulsory Intimation of Infectious Diseases.

PMID- 29647712
TI  - Experiments on the Power of the Lochia to Produce Inflammation and Fever: Beitr.
      z. vergleich. u. Exp. Geburtsh.-Giessen, 1875.

PMID- 29647713
TI  - Contagiousness of Hereditary Syphilis.

PMID- 29647714
TI  - Speedy Cure of Severe Acute Disease of the Spinal Cord by Application of the
      Actual Cautery.

PMID- 29647715
TI  - Circulation in the Coronary Artery.

PMID- 29647716
TI  - Meetings of Societies.

PMID- 29647717
TI  - Observations Demonstrating the Influence of Digestion in the Mother upon the
      Frequency of the Foetal Pulse.

PMID- 29647718
TI  - The Systematic Education of the Insane.

PMID- 29647719
TI  - Case of Lymphatic Inflammation Simulating Venereal Disease.

PMID- 29647720
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29647721
TI  - A Case of Pleuritic Effusion Cured by Antiseptic Treatment.

PMID- 29647723
TI  - Somnambulism Artificially Produced: Journ. de l'Anant., etc., 1875.

PMID- 29647722
TI  - Diphtheria: Typical Cases, in Illustration of Its Diagnosis, Prognosis, and
      Treatment; Together with Remarks on the Signification of Albuminuria in That
      Disease.

PMID- 29647724
TI  - On the Treatment of a Severe Form of the So-Called "Paludal Fever," with Icterus
      and Renal Haemorrhage.

PMID- 29647725
TI  - Excision of a Migratory Gall-Stone.-Bayer, arztl. Intelligenzbl., 1875, No. 41.

PMID- 29647727
TI  - Correspondence.

PMID- 29647726
TI  - Reports of Cases Treated in Leith Hospital.

PMID- 29647728
TI  - Fibrous Tumour of the Lobe of the Ear, etc.

PMID- 29647730
TI  - Treatment of Meniere's Disease with Quinine.

PMID- 29647729
TI  - Note on the Comparative Weight of the Bones of the Superior Extremities;
      Application in Medical Jurisprudence.-Gaz. Hebdom. 1875, No. 36.

PMID- 29647731
TI  - The Structure of a True Mucous Polypus of the Cervix.

PMID- 29647732
TI  - Meetings of Societies.

PMID- 29647733
TI  - On the Reflex Functions of the Spinal Cord.

PMID- 29647734
TI  - On the Practice of Medical Jurisprudence. No. IV.

PMID- 29647736
TI  - Coca.

PMID- 29647735
TI  - Case in Which a Reducible Oblique and Direct Inguinal and Femoral Hernia Existed
      on the Same Side, and Were Successfully Treated by Operation.

PMID- 29647737
TI  - On the Life of William Hunter: The Harveian Address, 13th April 1876.

PMID- 29647738
TI  - Notes on an Interesting Case of Pneumo-Thorax.

PMID- 29647739
TI  - Diphtheria: Typical Cases, in Illustration of Its Diagnosis, Prognosis, and
      Treatment; Together with Remarks on the Signification of Albuminuria in That
      Disease.

PMID- 29647740
TI  - Refracture in Cases of Deformity from Badly-Adjusted Fracture.

PMID- 29647742
TI  - Case of Excision of the Elbow-Joint.

PMID- 29647741
TI  - Scrofulous Sores or Runnings.

PMID- 29647743
TI  - A Case of Torpor of the Liver and Bowels from Birth, and Consequent Persistent
      Constipation, in a Boy Six Years Old; Recovery.

PMID- 29647744
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29647746
TI  - On the Alleged Occasional Epidemic Prevalence of Puerperal Pyaemia or Puerperal
      Fever, and of Erysipelas.

PMID- 29647745
TI  - List of Successful Army Medical Candidates.

PMID- 29647747
TI  - On Inflammation. Chapter IV.

PMID- 29647748
TI  - Diphtheria: Typical Cases, in Illustration of Its Diagnosis, Prognosis, and
      Treatment; Together with Remarks on the Significance of Albuminuria in That
      Disease.

PMID- 29647750
TI  - Remarks on the Inevitable and Other Lacerations of the Orifice of the Vagina, and
      near It, in Primiparae.

PMID- 29647749
TI  - On Conservative Aural Surgery.

PMID- 29647751
TI  - Surgical Note on a New Method of Applying Sayre's Knee-Joint Splint.

PMID- 29647753
TI  - Meetings of Societies.

PMID- 29647752
TI  - Case of Fibro-Cystic Tumour of Uterus; Removal of Uterus and Ovaries.

PMID- 29647754
TI  - Method of Preparing Raw Meat.

PMID- 29647756
TI  - Case of Anaemia Perniciosa.

PMID- 29647755
TI  - On the Presence of Sugar in Healthy Blood.

PMID- 29647757
TI  - Scarlatinal Arthritis.

PMID- 29647758
TI  - Acute Osteomyelitis of the Spine.

PMID- 29647759
TI  - Letter from Vienna.

PMID- 29647760
TI  - Application of the Bronchoscope in the Diagnosis and Treatment of Certain
      Affections of the Chest.

PMID- 29647761
TI  - The Attitude of the Medical Profession to Scientific Problems.

PMID- 29647762
TI  - The Treatment of Empyema in Children.

PMID- 29647763
TI  - The Sippy Treatment of Peptic Ulcers.

PMID- 29647764
TI  - A Case of Congenital Defect of the Thoracico-Cervical Spine.

PMID- 29647765
TI  - Periarterial Sympathectomy.

PMID- 29647766
TI  - A Case of Fracture of the Olecranon, Treated by Temporary Pressure Paralysis of
      the Musculo-Spiral Nerve.

PMID- 29647767
TI  - Clinical Meeting.

PMID- 29647768
TI  - Notes.

PMID- 29647769
TI  - Hypopituitarism Associated with Glycosuria.

PMID- 29647770
TI  - Medicina Antiqua.

PMID- 29647771
TI  - Causalgia Treated by Modified Periarterial Sympathectomy.

PMID- 29647772
TI  - Notes on a Case of Tubal Twin Pregnancy.

PMID- 29647773
TI  - An Investigation upon the Value of Two Methods of Estimating Nutrition in Infancy
      (The Pirquet Method, and the W/H to Height-Age Method).

PMID- 29647774
TI  - A Consideration of the Round or Stoop Shoulder Deformity, with Report of an
      Aggravated Case.

PMID- 29647775
TI  - On the Symptoms and Home Treatment of Mentally Defective Infants and Young
      Children.

PMID- 29647776
TI  - Discussion on Congenital or Inherited Syphilis.

PMID- 29647777
TI  - Traversing Wounds of the Orbit.

PMID- 29647778
TI  - Some Biological and Economic Aspects of Comparative Pathology.

PMID- 29647779
TI  - Septic Otitic Thrombosis of the Cranial Blood Sinuses and Jugular Bulb.

PMID- 29647781
TI  - Exhibition of Specimens.

PMID- 29647780
TI  - Case of Traumatic Involvement of Meckel's Diverticulum.

PMID- 29647782
TI  - A Case of Multiple Traumatic Perforations of the Small Intestine without Any
      Penetrating Wound of the Abdominal Wall.

PMID- 29647783
TI  - Alimentary Sepsis from the Practitioner's Point of View: Chalmers Watson: With
      Demonstration.

PMID- 29647784
TI  - Clinical Meeting.

PMID- 29647785
TI  - Simple Ulcers of the Jejeunum and Ileum: With Notes of Two Cases.

PMID- 29647786
TI  - Valedictory Address.

PMID- 29647787
TI  - The Clinical Significance of the Form and Capacity of the Renal Pelvis : With
      Lantern Demonstrations.

PMID- 29647788
TI  - The Spirit of Leisure and the Spirit of Work : Some Aspects of a Modern "Religio
      Medici".

PMID- 29647790
TI  - Exhibition of Cases.

PMID- 29647789
TI  - Congenital High-Scapula, with Which Is Included a Consideration of Brevicollis.

PMID- 29647791
TI  - A Review of Certain Aspects in the Newer Methods of the Treatment of
      Tuberculosis.

PMID- 29647792
TI  - The Complement-Fixation Test in the Diagnosis of Tuberculosis, with Special
      Reference to Pulmonary Tuberculosis.

PMID- 29647793
TI  - A Case of Acute Myeloblastic Leukaemia.

PMID- 29647794
TI  - Tuberculin in the Diagnosis and Treatment of Tuberculosis.

PMID- 29647795
TI  - The Place of the Sanatorium in the Tuberculosis Scheme.

PMID- 29647796
TI  - The Treatment of Surgical Tuberculosis.

PMID- 29647797
TI  - Some Observations on Maternal Mortality.

PMID- 29647798
TI  - Radiology in the Diagnosis of Pulmonary Tuberculosis : A Discussion and X-Ray
      Demonstration at Ruchill Hospital, Glasgow.

PMID- 29647799
TI  - Some Aspects of the Tuberculosis Problem from the Experimental and Comparative
      Standpoint.

PMID- 29647800
TI  - Analytical Notes.

PMID- 29647801
TI  - Syphilis of the Lung.

PMID- 29647802
TI  - Maternal Morbidity in the Light of Experience from the Maternity Hospital.

PMID- 29647803
TI  - Some Aspects of the Diagnosis of Renal Tuberculosis.

PMID- 29647804
TI  - Case of Aplastic Anaemia.

PMID- 29647805
TI  - Historical Note: The Discovery of Sarcina Ventriculi, 1842.

PMID- 29647807
TI  - A House Surgeon's Memories of Lister.

PMID- 29647806
TI  - Glandular Fever (Infectious Mononucleosis).

PMID- 29647808
TI  - Notes.

PMID- 29647809
TI  - Angina Pectoris Treated with Testosterone.

PMID- 29647810
TI  - Urogenital Tuberculosis.

PMID- 29647812
TI  - Thomas Dover, 1660-1742.

PMID- 29647811
TI  - Temporary Cardiac Arrest for Twenty Minutes.

PMID- 29647813
TI  - Acute Intestinal Obstruction from the Clinical Standpoint.

PMID- 29647814
TI  - Mammary Carcinoma with Cutaneous Carcinosis of Erysipelatodes Type.

PMID- 29647815
TI  - Vitamin K in the Newborn.

PMID- 29647816
TI  - Observations on Eclamptic Toxaemia and on Essential Hypertension and Chronic
      Nephritis in Pregnancy.

PMID- 29647817
TI  - Dover's "Legacy".

PMID- 29647818
TI  - The Medical Preliminary and after.

PMID- 29647819
TI  - The Treatment of Cerebro-Spinal Fever by Sulphapyridine.

PMID- 29647820
TI  - The Problem of Air-Borne Infection.

PMID- 29647821
TI  - A Simple Test for Headaches.

PMID- 29647822
TI  - The Royal Infirmary of Edinburgh: Payments by Patients in the Eighteenth Century.

PMID- 29647823
TI  - Sustained Controlled Hyperpyrexia Therapy.

PMID- 29647824
TI  - Post-Concussion Headache-New Treatment.

PMID- 29647825
TI  - Review of Irradiation Effect on Cells and Tissues of the Skin.

PMID- 29647826
TI  - Combined Inductopyrexia and Chemotherapy in the Treatment of Resistant
      Gonorrhoea.

PMID- 29647827
TI  - Pernicious Anaemia: Some Vital Considerations.

PMID- 29647828
TI  - The Contribution of the Emergency Medical Service to Medicine and Surgery in
      Scotland.

PMID- 29647829
TI  - Spinal Atrophic Paralysis.

PMID- 29647830
TI  - Chronic Fluorine Poisoning (Fluorosis) Signs and Symptoms.

PMID- 29647831
TI  - The Problem of Peri-Rectal Suppuration.

PMID- 29647832
TI  - Concerning Cancer.

PMID- 29647833
TI  - Notes.

PMID- 29647835
TI  - Treatment of Delirium Tremens.

PMID- 29647834
TI  - The Differential Diagnosis of the Chronic Affections of the Lungs.

PMID- 29647837
TI  - Sleep Paralysis.

PMID- 29647836
TI  - Body Snatching in 1742.

PMID- 29647838
TI  - Studies in Method and Standardisation of Blood Examination. IX. Size and Site of
      Sample in the Differential Leucocyte Count.

PMID- 29647840
TI  - On Ossification and Vitamin D Action.

PMID- 29647839
TI  - The Surgery of the Hypopharynx: Post-Cricoid Carcinoma.

PMID- 29647841
TI  - The Common Cold.

PMID- 29647842
TI  - The Surgery of the Hypopharynx: Pharyngeal Pouch.

PMID- 29647843
TI  - Popular Misconceptions in Connection with the Eyes.

PMID- 29647844
TI  - Prostatic Enlargement.

PMID- 29647845
TI  - Auricular Standstill.

PMID- 29647846
TI  - Notes on the Carotid Body.

PMID- 29647847
TI  - Diabetic Coma: Recovery in a Case with Blood Sugar of 1600 Mgms. Per Cent.

PMID- 29647848
TI  - The Excretion of Vitamin A in Urine.

PMID- 29647849
TI  - Progressive Middle Ear Deafness.

PMID- 29647850
TI  - Notes.

PMID- 29647851
TI  - Halitosis.

PMID- 29647853
TI  - Insulin Resistance.

PMID- 29647852
TI  - Some Aspects of OEstrogenic Therapy.

PMID- 29647854
TI  - John Hunter: Surgeon and Naturalist.

PMID- 29647855
TI  - A Contribution to the Pathogenesis of Spondylitis Ankylopoietica.

PMID- 29647856
TI  - Primary New Growths of the Lung.

PMID- 29647857
TI  - A Hundred Years Ago: On a New Remedy for Scalds and Burns, 1842.

PMID- 29647859
TI  - Sarcoidosis: A Review Based on a Case of the Disease.

PMID- 29647858
TI  - Notes.

PMID- 29647860
TI  - The Development of Materia Medica in Edinburgh: Inaugural Address.

PMID- 29647861
TI  - The Incidence of Bromide Medication; a Study of 1026 Admissions.

PMID- 29647863
TI  - The Influence of Atropin upon Complete Heart Block, Transient and Intermittent.

PMID- 29647862
TI  - Studies on Stored Blood: X. Complement, Iso-Agglutinins and Agglutinogens.

PMID- 29647864
TI  - The Arrest of Dental Caries.

PMID- 29647865
TI  - Dysentery Carriers Treated with Sulphaguanidine.

PMID- 29647866
TI  - Surgical Lesions of the Spinal Cord and Nerve-Roots.

PMID- 29647867
TI  - Macro- and Micro-Diagnosis of Cancer. A Laboratory Survey of Routine Mammary
      Lesions.

PMID- 29647868
TI  - Obesity Treated with Benzedrine Sulphate.

PMID- 29647869
TI  - Some Recent Advances in Chemotherapy.

PMID- 29647870
TI  - The Bio-Chemical Control of Cancer.

PMID- 29647871
TI  - Notes.

PMID- 29647872
TI  - Epilepsy Wrongly Diagnosed Is a Horrible Thing!

PMID- 29647873
TI  - A New Use for Digitalis.

PMID- 29647874
TI  - Osteochondritis and Tuberculosis : A Demonstration of Cases of Calve's Disease of
      the Spine and Kohler's Disease of the Tarsal Scaphoid, with a Discussion on Their
      Relationship to Tuberculosis.

PMID- 29647875
TI  - The Footprints of Surgery: Inaugural Address to the Royal Medical Society on 17th
      October 1941.

PMID- 29647877
TI  - Experiences in an E.M.S. Base Hospital in the London Area.

PMID- 29647876
TI  - Synthetic Vitamin E in the Treatment of Abortion.

PMID- 29647878
TI  - Corrigenda.
AB  - [This corrects the article on p. 40 in vol. 49.].

PMID- 29647879
TI  - Pruritus Vulvae Treated by Acid Stilboestrol Cream.

PMID- 29647880
TI  - Magnesium Sulphate in the Hypertension of Acute Nephritis.

PMID- 29647881
TI  - Egg Yolk Powder as a Weight-Increasing Agent.

PMID- 29647882
TI  - Studies on Stored Blood: IX. Further Observations on the Effects of Storage on
      Erythrocytes.

PMID- 29647883
TI  - Case of Abdominal Lymphadenoma, with Transposition of Viscera and Nine Accessory
      Spleens.

PMID- 29647884
TI  - Expectorants and Anti-Expectorants.

PMID- 29647886
TI  - Notes.

PMID- 29647885
TI  - Medical Education in Scotland.

PMID- 29647887
TI  - The Royal Infirmary: 1742.

PMID- 29647888
TI  - The Congo Red Test for Amyloidosis.

PMID- 29647889
TI  - "Egg-White Injury" in Man.

PMID- 29647890
TI  - Tuberculosis and Derangement of Suprarenal Function.

PMID- 29647891
TI  - Intravenous Therapy with Invert Sugar.

PMID- 29647892
TI  - The Length of the Menstrual Cycle.

PMID- 29647894
TI  - Arterio-Sclerosis and Varicose Veins.

PMID- 29647893
TI  - Auricular Flutter with a 1:1 Auriculo-Ventricular Response.

PMID- 29647895
TI  - Delinquency.

PMID- 29647896
TI  - The Determination of the Blood Volume in Man with Evans Blue ("T-1824").

PMID- 29647897
TI  - The Influence of Certain Antacids on the Acidity of Human Gastric Juice, with
      Special Reference to Magnesium Trisilicate.

PMID- 29647898
TI  - Blood Pressure, Normal and Abnormal.

PMID- 29647900
TI  - Fractures of the Neck of the Femur. Their Treatment: A Review.

PMID- 29647899
TI  - Studies in Method and Standardisation of Blood Examination: VI. The Blood
      Platelet Film Count.

PMID- 29647901
TI  - The Psychological Aspect of Physical Education.

PMID- 29647902
TI  - A Hundred Years Ago: Blood Transfusion in 1837.

PMID- 29647903
TI  - The Syndrome of Crocodile Tears.

PMID- 29647905
TI  - An Emergency Blood Transfusion Service.

PMID- 29647904
TI  - Some Reflections on Two Recent Publications on Rickets.

PMID- 29647906
TI  - The Pathological Significance of Intra-Articular Pressure.

PMID- 29647907
TI  - Vitamin K.

PMID- 29647908
TI  - Migraine and Biliousness.

PMID- 29647909
TI  - A Hundred Years Ago.

PMID- 29647911
TI  - Notes.

PMID- 29647910
TI  - The Tarry Stool of Melaena.

PMID- 29647912
TI  - A Hundred Years Ago: Clinical Records.

PMID- 29647913
TI  - Notes.

PMID- 29647914
TI  - The Medical Faculty 200 Years Ago.

PMID- 29647915
TI  - Ulcerative Colitis-Medical versus Surgical Treatment.

PMID- 29647916
TI  - Notes.

PMID- 29647917
TI  - Hypogonadism-Oral Therapy.

PMID- 29647918
TI  - Chordoma.

PMID- 29647919
TI  - Mitral Stenosis in the Aged.

PMID- 29647920
TI  - The Dietetic Treatment of Gastro-Intestinal Disease.

PMID- 29647921
TI  - The Hypertensions.

PMID- 29647922
TI  - Surgical Aspects of Diseases of the Chest.

PMID- 29647923
TI  - Inductopyrexia: Its Technique and Application.

PMID- 29647924
TI  - Medical Education in Scotland.

PMID- 29647925
TI  - The Future of Post-Graduate Teaching.

PMID- 29647927
TI  - The Significance of Systolic Murmurs.

PMID- 29647926
TI  - The Pulse Rate in Acute Juvenile Rheumatism.

PMID- 29647928
TI  - Notes.

PMID- 29647929
TI  - Surgical Experiences in the Zulu and Transvaal Wars, 1879 and 1881.

PMID- 29647930
TI  - Royal Colleges of Physicians and Surgeons, Edinburgh.

PMID- 29647931
TI  - Senile Insanity.

PMID- 29647932
TI  - Meetings of Societies.

PMID- 29647933
TI  - Ankle Clonus in Relation to the Height of the Individual.

PMID- 29647934
TI  - Periscope of State Medicine.

PMID- 29647935
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29647936
TI  - Periscope of Laryngology.

PMID- 29647937
TI  - Surgical Periscope.

PMID- 29647938
TI  - Case of Double Ovariotomy; Unusually Long and Twisted Pedicle; Note on the
      Question of Early Operations.

PMID- 29647939
TI  - University of Edinburgh, List of Graduates.

PMID- 29647940
TI  - Remarks on Retroversion of the Gravid Uterus.

PMID- 29647941
TI  - Quarterly Report of the Royal Maternity and Simpson Memorial Hospital.

PMID- 29647942
TI  - The Examination of Deaf-Mutes.

PMID- 29647943
TI  - Acute Circumscribed Cutaneous OEdema.

PMID- 29647944
TI  - Carmedik, a Cape Bitter; Its Characters and Chemistry.

PMID- 29647945
TI  - Umbilical Cord Round the Child's Neck as a Cause of Delayed Labour, and Sometimes
      of Infantile Death.

PMID- 29647946
TI  - A Fourth Case of Resuscitation of the Still-Born Infant.

PMID- 29647947
TI  - Meetings of Societies.

PMID- 29647948
TI  - Unusual Case of Strangulated Congenital Hernia.

PMID- 29647949
TI  - On the Use of Chian Turpentine in Cases of Uterine Carcinoma.

PMID- 29647950
TI  - Resection of the Long Bones.

PMID- 29647951
TI  - New Mode of Reducing Dislocations of Shoulder and Hip.

PMID- 29647952
TI  - Original Research in Sanitary Science.

PMID- 29647953
TI  - The Examination of Deaf-Mutes.

PMID- 29647954
TI  - Occasional Periscope of Dermatology.

PMID- 29647955
TI  - Dr K. M'Leod on Cure of Hernia.

PMID- 29647957
TI  - Professor Bennett on Plastic Surgery and Fracture of Metacarpal Bones.

PMID- 29647956
TI  - Notes on Typhoid Fever, Suggested by a Recent Epidemic at Newton Heath,
      Manchester.

PMID- 29647958
TI  - Management of Chronic Inebriates, etc.

PMID- 29647959
TI  - University of Edinburgh: First Professional Examination.

PMID- 29647961
TI  - Internal OEsophagotomy.

PMID- 29647960
TI  - Royal Colleges of Physicians and Surgeons, Edinburgh.

PMID- 29647962
TI  - Periscope of Syphilology.

PMID- 29647963
TI  - Superinvolution of the Uterus.

PMID- 29647964
TI  - Periscope of State Medicine.

PMID- 29647965
TI  - On a New Form of Respirator for Continuous Inhalation.

PMID- 29647966
TI  - Catalogue of Royal College of Surgeons.

PMID- 29647967
TI  - Connexion between Insanity and Alcoholism.

PMID- 29647968
TI  - Policlinical Institution in Berlin.

PMID- 29647969
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29647970
TI  - Surgical Experiences in the Zulu and Transvaal Wars, 1879 and 1881.

PMID- 29647971
TI  - Statistics of Operations in Mr Joseph Bell's Wards from 1st November 1882 to 1st
      April 1883.

PMID- 29647972
TI  - Midland Medical Miscellany.

PMID- 29647973
TI  - Royal College of Physicians, Edinburgh.

PMID- 29647974
TI  - Phthisis of the Larynx.

PMID- 29647975
TI  - Manslaughter.

PMID- 29647976
TI  - Morehead Memorial Fund.

PMID- 29647978
TI  - Periscope of Otology.

PMID- 29647977
TI  - Periscope of State Medicine.

PMID- 29647979
TI  - International Exhibition at Amsterdam: May-October 1883.

PMID- 29647980
TI  - On the Relationship of Some Forms of Integumentary Atrophy.

PMID- 29647981
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29647982
TI  - On the Therapeutic Value of Sulphurous Acid and Steel in Scarlatina Maligna.

PMID- 29647983
TI  - Meetings of Societies.

PMID- 29647985
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29647984
TI  - Address at the Opening of the Forty-Second Session of the Edinburgh Obstetrical
      Society.

PMID- 29647987
TI  - Periscope of Syphilology.

PMID- 29647986
TI  - Dr R. Newman on Stricture of the Rectum.

PMID- 29647988
TI  - Intra-Peritoneal Pelvic Haematocele: Clinical Lecture, Delivered at the Royal
      Infirmary, Edinburgh, on 17th November 1882.

PMID- 29647989
TI  - Occasional Periscope of Dermatology.

PMID- 29647990
TI  - The Examination of Deaf-Mutes.

PMID- 29647991
TI  - Periscope of State Medicine.

PMID- 29647992
TI  - The Legal and Medical Theories of Mental Disease in Criminal Cases.

PMID- 29647994
TI  - New Urethral Syringe.

PMID- 29647993
TI  - Monthly Retrospect of Obstetrics and Gynaecology.

PMID- 29647996
TI  - Erratum in November Number.
AB  - [This corrects the article on p. 444 in vol. 28.].

PMID- 29647995
TI  - Royal College of Physicians, Edinburgh.

PMID- 29647997
TI  - Occasional Periscope of Surgery and Surgical Pathology.

PMID- 29648000
TI  - Case of Tubercular Meningitis.

PMID- 29647998
TI  - Medical Notes and Statistics of the British Expedition to Egypt in 1801.

PMID- 29647999
TI  - Periscope of Otology.

PMID- 29648002
TI  - Report on Inebriates.

PMID- 29648001
TI  - A Movable Clot in the Right Auricle.

PMID- 29648003
TI  - Deaf-Muteism.

PMID- 29648004
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29648005
TI  - Medical Conference on Vaccination.

PMID- 29648006
TI  - A Personal Experience of Dislocation of the Humerus, and Its Lessons.

PMID- 29648007
TI  - How They Make Cod-Oil at Swampscott.

PMID- 29648008
TI  - Nasal Disease as a Cause of Asthma.

PMID- 29648009
TI  - On a Form of Loss of Memory Occasionally Following Cranial Injuries.

PMID- 29648011
TI  - Remarkable Surgical Cases.

PMID- 29648010
TI  - Correspondence.

PMID- 29648012
TI  - Meetings of Societies.

PMID- 29648013
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29648015
TI  - Royal College of Physicians, Edinburgh.

PMID- 29648014
TI  - The Prophylaxis of Ophthalmia Neonatorum.

PMID- 29648016
TI  - Meetings of Societies.

PMID- 29648017
TI  - Retirement of Dr Keiller.

PMID- 29648018
TI  - Dislocation of the Wrist-Joint, and Fracture of the Lower End of the Radius: A
      Clinical Lecture.

PMID- 29648019
TI  - Treatment of Hysteria by Metallo-Therapy.

PMID- 29648020
TI  - Diphtheria.

PMID- 29648021
TI  - Periscope of State Medicine.

PMID- 29648022
TI  - Occasional Periscope of Dermatology.

PMID- 29648023
TI  - Observations on the Bladder during the Early Puerperium.

PMID- 29648024
TI  - Royal Maternity Hospital Report for Quarter 1st August to 31st October 1882.

PMID- 29648025
TI  - List of Candidates for H.M. British Medical Service.

PMID- 29648026
TI  - The Opium Question.

PMID- 29648027
TI  - Occasional Periscope of Surgery and Surgical Pathology.

PMID- 29648028
TI  - Note of a Case of Inversion of the Uterus Occurring Immediately Post-Partum, and
      Resulting in Spontaneous Amputation.

PMID- 29648029
TI  - Monthly Retrospect of Obstetrics and Gynaecology.

PMID- 29648030
TI  - Resection of Portions of Ribs.

PMID- 29648031
TI  - Astley Cooper Prize.

PMID- 29648032
TI  - The Physiological Action of Carbolic Acid, Illustrated by Its Use in Surgery.

PMID- 29648033
TI  - Periscope of Otology.

PMID- 29648034
TI  - Periscope of Ophthalmology.

PMID- 29648035
TI  - Note on Treatment of Warts on the Genitals by Chromic Acid.

PMID- 29648037
TI  - Occasional Periscope of Surgery and Surgical Pathology.

PMID- 29648036
TI  - On the Treatment of Leprosy.

PMID- 29648038
TI  - Occasional Periscope of Dermatology.

PMID- 29648039
TI  - Basilysis for Dystocia from Hypertrophic Elongation of the Cervix Uteri.

PMID- 29648040
TI  - Quarterly Abstracts of Papers on the Diseases of Children, No I.

PMID- 29648041
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29648042
TI  - Surgical Experiences in the Zulu and Transvaal Wars, 1879 and 1881.

PMID- 29648044
TI  - Royal Colleges of Physicians and Surgeons, Edinburgh.

PMID- 29648043
TI  - A Curious Instance of Cadaveric Spasm.

PMID- 29648045
TI  - Periscope of Syphilology.

PMID- 29648046
TI  - Meetings of Societies.

PMID- 29648047
TI  - Royal College of Physicians, Edinburgh.

PMID- 29648048
TI  - Sequelae of Tracheotomy Occurring after Closure of Tracheal Wound.

PMID- 29648050
TI  - An Improved Method of Circumcision for Congenital Phimosis.

PMID- 29648049
TI  - On Dangerous Haemorrhage from the External Genital Organs during and after
      Labour.

PMID- 29648051
TI  - Germs and the Spray.

PMID- 29648052
TI  - Case of Strangulated Congenital Inguinal Hernia.

PMID- 29648053
TI  - Inco-Ordinate Uterine Action in Labour.

PMID- 29648054
TI  - Streptomycin Treatment of Meningeal, Miliary and Pulmonary Tuberculosis.

PMID- 29648055
TI  - Two Cases of Congenital Abnormalities of the Genital Tract Associated with
      Pregnancy.

PMID- 29648056
TI  - Anaesthesia for Caesarean Section.

PMID- 29648057
TI  - Caudal Analgesia for the Relief of Pain in Labour.

PMID- 29648058
TI  - Subacute Bacterial Endocarditis and Its Treatment with Penicillin.

PMID- 29648059
TI  - Inaugural Lecture.

PMID- 29648060
TI  - Acute Infections of the Hand.

PMID- 29648061
TI  - Report on Cases Treated with P.A.S. at Robroyston Hospital, Glasgow.

PMID- 29648062
TI  - Vaginal Hysterectomy.

PMID- 29648064
TI  - Exostosis of the Orbit.

PMID- 29648063
TI  - Report of Cases Treated with P.A.S. at Robroyston Hospital, Glasgow.

PMID- 29648065
TI  - The Morbid Anatomy and Histology of Pellagra.

PMID- 29648066
TI  - Thrombo-Angiitic Gangrene.

PMID- 29648067
TI  - The Use of Massive Doses of Digitalis.

PMID- 29648068
TI  - Causes of Hydronephrosis.

PMID- 29648070
TI  - Notes.

PMID- 29648069
TI  - A Note on a Severe Type of Scarlatinal Nephritis.

PMID- 29648071
TI  - A Note on Renal Function in Scarlet Fever.

PMID- 29648072
TI  - Iodine in the Treatment of Goitre.

PMID- 29648073
TI  - An Unusual Cause of Exophthalmos.

PMID- 29648074
TI  - Spinal Anaesthesia in the Treatment of Post-Operative Ileus.

PMID- 29648075
TI  - Syringomyelia.

PMID- 29648076
TI  - Clinical Meeting.

PMID- 29648077
TI  - Movable Kidney.

PMID- 29648078
TI  - Discussion on Endocrine Therapy.

PMID- 29648079
TI  - A Preliminary Report on the Radiographic Exploration of the Broncho-Pulmonary
      System by Means of Lipiodol.

PMID- 29648081
TI  - Dr James Mounsey of Rammerscales.

PMID- 29648080
TI  - Oxycephaly.

PMID- 29648082
TI  - Post-Mortem Tuberculous Lesions: Their Prevalence and Distribution in 404
      Consecutive Examinations Conducted at the Royal Infirmary, Edinburgh.

PMID- 29648084
TI  - Analytical Note.

PMID- 29648083
TI  - Eye Symptoms and Signs in the Diagnosis of General Disease.

PMID- 29648085
TI  - A Clinical Method for the Estimation of Calcium in the Blood and Urine.

PMID- 29648087
TI  - Studies on the Parathyreoids.

PMID- 29648086
TI  - The Action of Colloidal Gum Benzoin on Syphilitic and Non-Syphilitic Human Sera.

PMID- 29648088
TI  - Comradeship in Science.

PMID- 29648089
TI  - Results of Suprapubic Prostatectomy.

PMID- 29648090
TI  - A Simple Treatment for Cutaneous Papilloma.

PMID- 29648091
TI  - Valedictory Address.

PMID- 29648093
TI  - Carcinoma of the Colon: Its Incidence, Treatment, and End-Results.

PMID- 29648094
TI  - Oxycephaly.

PMID- 29648092
TI  - The Progressive Arterial Changes in Hydronephrosis: An Experimental Study,
      Obtained on the Rabbit, and Illustrating These Changes in the Simple Unilobed
      Type of Kidney.

PMID- 29648096
TI  - Subphrenic Abscess.

PMID- 29648095
TI  - The Diagnosis of Cancer of the Stomach.

PMID- 29648097
TI  - Results of Gastrectomy for Cancer.

PMID- 29648098
TI  - Three Cases of Severe Infection Treated by Immunotransfusion.

PMID- 29648099
TI  - The Relationship of the Thymus and Testes to Growth.

PMID- 29648100
TI  - James Lind and Scurvy.

PMID- 29648102
TI  - Thrombopaenic Purpura Haemorrhagica.

PMID- 29648101
TI  - The Value of Sgambatti's Test in the Detection of Inflammatory Infections of the
      Peritoneum in Children.

PMID- 29648103
TI  - Accidental Inoculation of a Malignant Tumour in Man.

PMID- 29648104
TI  - Some Statistical Aspects of Tuberculous Meningitis.

PMID- 29648105
TI  - Pulmonary Tuberculosis and Allied Conditions in Infancy and Childhood.

PMID- 29648106
TI  - The Serology of the Tubercle Bacillus-Present Position.

PMID- 29648107
TI  - Specimens Illustrative of Early Tuberculosis in Cows.

PMID- 29648108
TI  - The Prognosis of Middle-Ear Suppuration in Children.

PMID- 29648109
TI  - The Virulence of Tuberculous Viruses.

PMID- 29648110
TI  - On the Use of Light in the Treatment of Tuberculosis.

PMID- 29648111
TI  - Sanocrysin.

PMID- 29648112
TI  - A Study of the Reaction Curve of One Hundred and Seventeen Strains of Tubercle
      Bacilli.

PMID- 29648113
TI  - The Treatment of Renal Tuberculosis from the Standpoint of the Surgeon.

PMID- 29648115
TI  - Adiposity and Other Etiological Factors in Diabetes Millitus.

PMID- 29648114
TI  - The Production of Certified Milk.

PMID- 29648117
TI  - Results of Treatment of Jacksonian Epilepsy.

PMID- 29648118
TI  - Effects Produced by Substitution.

PMID- 29648116
TI  - Haemoglobinuria in Acetic Acid Poisoning.

PMID- 29648119
TI  - Oxycephaly.

PMID- 29648120
TI  - Parathyreoids and Osteitis Fibrosa.

PMID- 29648121
TI  - Physiology of the Endocrine Glands.

PMID- 29648122
TI  - Tumours of the Glandula Carotica.

PMID- 29648123
TI  - Periarterial Sympathectomy.

PMID- 29648125
TI  - Function after Colectomy.

PMID- 29648124
TI  - Post-Mortem Tuberculous Lesions : Their Prevalence and Distribution in 404
      Consecutive Examinations Conducted at the Royal Infirmary, Edinburgh.

PMID- 29648126
TI  - Some Pharmacological and Metabolic Actions of Certain Endocrine Products.

PMID- 29648127
TI  - Haemorrhagic Pancreatitis.

PMID- 29648128
TI  - Unilateral Abdominal Amyoplasia.

PMID- 29648129
TI  - On Normal Variations in the Cutaneous Temperature of the Extremities.

PMID- 29648130
TI  - The Retinal Circulation in Cardio-Vascular Renal Disease.

PMID- 29648131
TI  - Notes.

PMID- 29648132
TI  - Disuse Post-Traumatic Decalcification.

PMID- 29648133
TI  - The Morbid Miner.

PMID- 29648134
TI  - Sex Hormone Therapy in Gynaecology.

PMID- 29648135
TI  - Post-Traumatic Osteoma.

PMID- 29648136
TI  - Parathyreoidectomy in Ankylosing Polyarthritis.

PMID- 29648137
TI  - The Problem of the Industrial Cripple, Surveyed Especially in the South-East of
      Scotland.

PMID- 29648138
TI  - A Preliminary Communication Regarding the Progress Made by the Medical Side of
      the Department of Physical Education, University of Edinburgh.

PMID- 29648139
TI  - On So-Called "Spontaneous Arachnoid Haemorrhages".

PMID- 29648140
TI  - Some Modern Problems Connected with the Cerebro-Spinal Fluid.

PMID- 29648141
TI  - Observations on Primary Lung Carcinoma.

PMID- 29648143
TI  - The Hypothalamus: A Report of the Henderson Trust Lectures.

PMID- 29648142
TI  - Remarks upon the Symptom of Cough in Relation to Chronic and Acute Illness in
      Childhood.

PMID- 29648144
TI  - Pigmentation Due to Perfume.

PMID- 29648146
TI  - The Philosophy of a Doctor.

PMID- 29648145
TI  - Corynebacterium Diphtheriae in Edinburgh: The Incidence of Types among Cases and
      Carriers from 1932-1936.

PMID- 29648147
TI  - Alcoholism and Psychiatry.

PMID- 29648148
TI  - Bone and the Carotic Glomus.

PMID- 29648149
TI  - The Pupil after Cervico-Thoracic Sympathetic Ganglionectomy: Photographic
      Observations in Man.

PMID- 29648150
TI  - Post-Operation Foreign Body in Abdomen.

PMID- 29648151
TI  - The Effect of Early Tonsillectomy on the Incidence of Acute Rheumatism.

PMID- 29648153
TI  - The Royal Infirmary of Edinburgh-The New Dermatological and Special Pavilion.

PMID- 29648152
TI  - Diabetes Insipidus. The Site of Formation of the Anti-Diuretic Hormone.

PMID- 29648154
TI  - Surgery in General Practice: Its Difficulties and Limitations.

PMID- 29648155
TI  - Notes.

PMID- 29648156
TI  - Cerebro-Spinal Fluid in Syphilis of the Central Nervous System.

PMID- 29648157
TI  - The Gall-Bladder in Animals.

PMID- 29648158
TI  - Harvey and Integration.

PMID- 29648160
TI  - Some Modern Problems Connected with the Cerebro-Spinal Fluid.

PMID- 29648159
TI  - The Immortal Memory of William Harvey.

PMID- 29648161
TI  - Chronic Progressive Hydrocephalus.

PMID- 29648162
TI  - Virus Bodies in Lymphogranuloma Inguinale (Climatic Bubo).

PMID- 29648164
TI  - The "Running" Nose.

PMID- 29648163
TI  - Studies on Carbohydrate Metabolism in Mental Disorders. I. Glucose Tolerance
      Tests in Manic-Depressive Insanity and Other Depressions.

PMID- 29648165
TI  - The Formation of Gallstones.

PMID- 29648167
TI  - Some Modern Problems Connected with the Cerebro-Spinal Fluid.

PMID- 29648166
TI  - Passages of Medical History. Edinburgh Medicine, 1680-1750.

PMID- 29648168
TI  - Medical Education in Scotland.

PMID- 29648170
TI  - Spondylolisthesis: With a Description of a New Method of Operative Treatment and
      Notes of Ten Cases.

PMID- 29648169
TI  - A Neglected Aspect of Medical Education.

PMID- 29648171
TI  - The Causation, Pathology and Therapeutics of Electrical Injuries.

PMID- 29648172
TI  - Notes.

PMID- 29648173
TI  - Clinical and Experimental Investigations.

PMID- 29648174
TI  - Interference of Intrinsic Pulmonary Mechanisms as a Potential Cause of Asthma.

PMID- 29648175
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29648176
TI  - An Experimental Inquiry into the Existence of a Sixth Sense: To Which Are Added,
      Researches upon the Psychal Functions of the Cerebrum, in Relation to All the
      Senses.

PMID- 29648177
TI  - Remarks on the More Prevalent and Important Diseases of China, Especially Acute
      Dysentery.

PMID- 29648179
TI  - Varieties.

PMID- 29648178
TI  - Medical Jurisprudence. Report of the Trial of Alexander Murray for Murder, in
      Which the Defence of Insanity Was Sustained.

PMID- 29648180
TI  - On the Gunshot Injuries Which Occur in Civil Practice, with Illustrative Cases.

PMID- 29648181
TI  - On the Comparative Influence of the Male and Female Parent upon the Progeny.

PMID- 29648182
TI  - On a Criticism of William Reid's Trial for Murder and Abortion.

PMID- 29648183
TI  - Aneurism of the Left Internal Carotid Artery.

PMID- 29648184
TI  - On the Cervix Uteri in Pregnancy.

PMID- 29648186
TI  - Royal College of Physicians' Conversazione.

PMID- 29648185
TI  - On the Cervix Uteri in Pregnancy.

PMID- 29648187
TI  - Midwifery.

PMID- 29648189
TI  - Two Cases of Tracheotomy on Account of Laryngeal Obstruction Produced by the
      Entrance of Foreign Bodies.

PMID- 29648188
TI  - On Pericarditis.

PMID- 29648190
TI  - Varieties.

PMID- 29648191
TI  - Medicine.

PMID- 29648192
TI  - Therapeutical Record.

PMID- 29648193
TI  - Surgery.

PMID- 29648194
TI  - Regulations of the London University.

PMID- 29648195
TI  - The Polmont Case.

PMID- 29648196
TI  - Case of Vicarious Menstruation in a Female Aged 53.

PMID- 29648197
TI  - The Pathology of Tuberculous Bone.

PMID- 29648198
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29648199
TI  - On a New Poison from the Interior of China.

PMID- 29648200
TI  - Suggestions on the Pathology and Treatment of Placenta Proevia.

PMID- 29648201
TI  - A Blundering Female Practitioner.

PMID- 29648202
TI  - Quarterly Report of Cases Occurring at the Edinburgh Eye Infirmary, 140, George
      Street.

PMID- 29648203
TI  - On Some Points in the Treatment and Clinical History of Asthma.

PMID- 29648204
TI  - Polmont Case.

PMID- 29648205
TI  - Report of a Case of Extirpation of the Tongue.

PMID- 29648206
TI  - Varieties.

PMID- 29648207
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29648208
TI  - Medicine.

PMID- 29648209
TI  - Hospital in Edinburgh for Sick Children.

PMID- 29648211
TI  - Surgery.

PMID- 29648210
TI  - Second Report on the Deaths among the Assured in the Standard Life Assurance
      Company, for the Period from 15th November 1850 to 15th November 1855.

PMID- 29648212
TI  - Extracts from the Unpublished Writings of the Late Mr John Bell, Surgeon.

PMID- 29648213
TI  - Case of Perforation of the Perineum.

PMID- 29648214
TI  - Hygiene.

PMID- 29648215
TI  - Case of Human Monstrosity.

PMID- 29648216
TI  - Trial of a Surgeon for Malpraxis-Important Decision.

PMID- 29648217
TI  - Skoda and His Critics.

PMID- 29648218
TI  - Case of Rupture of the Urinary Bladder.

PMID- 29648219
TI  - Case of Invagination of the Coecum and Appendix.

PMID- 29648220
TI  - Poor-Law Medical Grievance.

PMID- 29648221
TI  - Royal College of Physicians-Conversazione.

PMID- 29648222
TI  - Liverpool Medical Institution-Homoeopathy Agitation.

PMID- 29648223
TI  - Surgery.

PMID- 29648225
TI  - Varieties.

PMID- 29648224
TI  - On the Cervix Uteri in Pregnancy.

PMID- 29648226
TI  - An Experimental Inquiry into the Existence of a Sixth Sense: To Which Are Added,
      Researches upon the Psychal Functions of the Cerebrum, in Relation to All the
      Senses.

PMID- 29648227
TI  - Medicine.

PMID- 29648228
TI  - The Pathology of Tuberculous Bone.

PMID- 29648229
TI  - The Projected Medical School for the Army.

PMID- 29648230
TI  - Quarterly Report of Cases Occurring at the Edinburgh Eye Infirmary.

PMID- 29648231
TI  - Observations on the History of Lithotomy, and of the Treatment after the
      Operation.

PMID- 29648232
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29648233
TI  - Diphtheria.

PMID- 29648234
TI  - The General Council of Medical Education and Registration.

PMID- 29648236
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29648235
TI  - On the Natural Acid Reaction of the Urine, and on the Determination of the
      Proportions Therein of Uric Acid and Urea, as Applicable to Practical Medicine.

PMID- 29648238
TI  - Toxicology.

PMID- 29648237
TI  - Varieties.

PMID- 29648239
TI  - Note of a Case of Hoemorrhage from the Vagina.

PMID- 29648241
TI  - On the Influence of Exercise over Respiration and Pulsation; with Comments.

PMID- 29648240
TI  - Medicine.

PMID- 29648242
TI  - Branch Council for England, and Executive Committee.

PMID- 29648244
TI  - Medical Notes from the Continent: Or, Sketches of the Universities, Hospitals,
      Lunatic Asylums, and Mineral Baths of Holland, Belgium, Germany, and Austria.

PMID- 29648243
TI  - Therapeutical Record.

PMID- 29648245
TI  - The Medical Council.

PMID- 29648246
TI  - On the Change of Type Theory of Disease.

PMID- 29648247
TI  - Skoda and His Critics.

PMID- 29648248
TI  - Two Cases of Aneurism of the Descending Thoracic Aorta, Producing Obstruction of
      the Thoracic Duct.

PMID- 29648250
TI  - Medicine.

PMID- 29648249
TI  - An Experimental Inquiry into the Existence of a Sixth Sense: To Which Are Added,
      Researches upon the Psychal Functions of the Cerebrum, in Relation to All the
      Senses.

PMID- 29648251
TI  - Letter of Dr Jenner.

PMID- 29648252
TI  - Medico-Chirurgical Society of Edinburgh.

PMID- 29648253
TI  - The Pathology of Tuberculous Bone.

PMID- 29648254
TI  - Varieties.

PMID- 29648256
TI  - Midwifery.

PMID- 29648255
TI  - Royal College of Physicians' Conversazione.

PMID- 29648257
TI  - Royal Medical Society.-Annual Dinner.

PMID- 29648258
TI  - On the Varieties of Asthma.

PMID- 29648259
TI  - Public Vaccination.

PMID- 29648260
TI  - Treatment of Epilepsy.

PMID- 29648261
TI  - Medical News.

PMID- 29648262
TI  - Hydramnios: And the Source of the Liquor Amnii.

PMID- 29648264
TI  - Occasional Periscope of Surgery and Surgical Pathology.

PMID- 29648263
TI  - Periscope of Otology.

PMID- 29648265
TI  - On the Treatment of Fresh Wounds.

PMID- 29648266
TI  - Correspondence.

PMID- 29648267
TI  - Royal College of Physicians, Edinburgh.

PMID- 29648268
TI  - Meetings of Societies.

PMID- 29648269
TI  - Case of Intestinal Obstruction Treated by Opening the Abdomen.

PMID- 29648270
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29648271
TI  - The Causes, Results, and Treatment of Lacerations of the Cervix Uteri: Clinical
      Lecture, Delivered on the 2nd June 1882.

PMID- 29648272
TI  - Secret and Proprietary Medicines.

PMID- 29648273
TI  - A Case of Complicated Fatty Tumour.

PMID- 29648274
TI  - Alternation, Periodicity, and Relapse in Mental Diseases.

PMID- 29648276
TI  - On Some Points of Interest in Connexion with a Case of Drowning in Which No Water
      Was Found in the Stomach.

PMID- 29648275
TI  - Monthly Retrospect of Obstetrics and Gynaecology.

PMID- 29648277
TI  - Occasional Periscope of Dermatology.

PMID- 29648278
TI  - Royal Colleges of Physicians and Surgeons, Edinburgh.

PMID- 29648280
TI  - Occasional Periscope of Surgery and Surgical Pathology.

PMID- 29648279
TI  - The Action of the Auricles in Health and Disease.

PMID- 29648281
TI  - Occasional Periscope of Dermatology.

PMID- 29648284
TI  - Cases of Stricture of the Urethra.

PMID- 29648282
TI  - On a Rare Form of Senile Gangrene.

PMID- 29648283
TI  - Two Cases of Enucleation of Intra-Uterine Fibroids by Dr Matthews Duncan, in St
      Bartholomew's Hospital.

PMID- 29648285
TI  - The Murmurs of Debility in the Pulmonary and Tricuspid Areas.

PMID- 29648287
TI  - Meetings of Societies.

PMID- 29648286
TI  - Graviditas Serotina et Praecox.

PMID- 29648288
TI  - Periscope of Otology.

PMID- 29648289
TI  - Monthly Retrospect of Obstetrics and Gynaecology.

PMID- 29648290
TI  - Remarkable Case of Recovery after Injury to the Head.

PMID- 29648291
TI  - W. H. Schieffelin & Co.'s Soluble Pills and Granules.

PMID- 29648292
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29648293
TI  - Attempted Assassination of Dr John P. Gray.

PMID- 29648294
TI  - On the Uterine Sound.

PMID- 29648295
TI  - Case of Hyperpyrexia in Acute Rheumatism: Cold Bath; Recovery.

PMID- 29648296
TI  - List of Candidates for Appointments as Surgeons in H.M. Medical Service.

PMID- 29648297
TI  - Royal College of Physicians, Edinburgh.

PMID- 29648298
TI  - Dr Levis's Surgical Instruments.

PMID- 29648299
TI  - Address to Students.

PMID- 29648300
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29648301
TI  - The Medical Congress of Seville.

PMID- 29648302
TI  - Army Medical Department.

PMID- 29648303
TI  - A Modern Fable.

PMID- 29648304
TI  - Noises for Invalids.

PMID- 29648305
TI  - Indian Medical Service.

PMID- 29648306
TI  - Students' Cabinet of Materia Medica.

PMID- 29648307
TI  - Meetings of Societies.

PMID- 29648308
TI  - Medical Schools of Scotland.

PMID- 29648310
TI  - Information Regarding Medical Education and Examinations.

PMID- 29648309
TI  - Northern Sanitary Association, Liverpool.

PMID- 29648311
TI  - Monthly Retrospect of Obstetrics and Gynaecology.

PMID- 29648312
TI  - Periscope of Otology.

PMID- 29648313
TI  - The Radical Cure of Cancer.

PMID- 29648314
TI  - Occasional Periscope of Dermatology.

PMID- 29648315
TI  - Obstetrical Observations.

PMID- 29648316
TI  - Case Illustrating the Importance of Accurate Pelvimetry; with Description of a
      New Method.

PMID- 29648317
TI  - Foetid Parametric and Perimetric Abscess.

PMID- 29648318
TI  - Cranial Injuries.

PMID- 29648319
TI  - Report on the Treatment of Sixty Cases of Vesical Calculus.

PMID- 29648321
TI  - Athetosis and Athetoid Movements in the Insane.

PMID- 29648320
TI  - Quarterly Report of the Royal Maternity and Simpson Memorial Hospital from 1st
      November 1881 to 31st January 1882.

PMID- 29648322
TI  - The Chronic Carbolic Acid Poisoning of Surgeons.

PMID- 29648323
TI  - Occasional Periscope of Surgery and Surgical Pathology.

PMID- 29648324
TI  - Monthly Retrospect of Obstetrics and Gynaecology.

PMID- 29648325
TI  - Periscope of Otology.

PMID- 29648326
TI  - Report of Cases Treated at the Ear Dispensary, 6 Cambridge Street, Lothian Road,
      from July 1880 to End of June 1881.

PMID- 29648327
TI  - A Case of Successful Sponge-Grafting.

PMID- 29648328
TI  - Points of Resemblance between Typhoid Fever and Diphtheria.

PMID- 29648330
TI  - List of Graduates at the Royal Colleges of Physicians and Surgeons, Edinburgh.

PMID- 29648329
TI  - Periscope of Syphilology.

PMID- 29648332
TI  - Meetings of Societies.

PMID- 29648331
TI  - Dr John Brown's Horae Subsecivae.

PMID- 29648333
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29648334
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29648335
TI  - Case of Accidental Poisoning by Cyanide of Potassium.

PMID- 29648336
TI  - On a Force Capable of Transmission beyond the Body without Sensible Effort.

PMID- 29648337
TI  - Opening Address to the Students Attending the Edinburgh School of Medicine:
      Delivered 24th October 1881.

PMID- 29648338
TI  - The Treatment of Syphilis.

PMID- 29648339
TI  - Ozena.

PMID- 29648340
TI  - Note on Rupture of the Urethra and Its Treatment.

PMID- 29648341
TI  - On Pityriasis Rosea, Maculata, et Circinata.

PMID- 29648343
TI  - On Vaccinal Skin Eruptions.

PMID- 29648342
TI  - Periscope of Otology.

PMID- 29648344
TI  - Diaphoresis in the Treatment of Blood-Diseases.

PMID- 29648347
TI  - Three Cases of Amputation at the Hip-Joint.

PMID- 29648346
TI  - Gleanings from My Midwifery Case-Book.

PMID- 29648345
TI  - Case of Hyperalgesia of the Lower Extremities: Followed by Pointing of an Abscess
      below Poupart's Ligament and Terminating Favourably.

PMID- 29648348
TI  - Another View of Congress.

PMID- 29648349
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29648350
TI  - M'Alpine's Zoological Atlas.

PMID- 29648351
TI  - Occasional Periscope of Dermatology.

PMID- 29648352
TI  - University of Edinburgh: Medical and Science Degrees.

PMID- 29648353
TI  - Meetings of Societies.

PMID- 29648355
TI  - Funeral of the Dead Doctor.

PMID- 29648354
TI  - Case of Paralysis of Musculo-Spinal Nerve from Pressure of Fragment of Bone:
      Excision of Fragment; Recovery.

PMID- 29648356
TI  - Funic Haemorrhage during Labour.

PMID- 29648357
TI  - A Case of Scarlet Fever Complicated by Acute Mania.

PMID- 29648358
TI  - Surgical Notes.

PMID- 29648359
TI  - Diseases Which Involve the Organ of Hearing.

PMID- 29648360
TI  - Dr J. H. Hutchison on Alcoholism.

PMID- 29648361
TI  - Induction of Premature Labour in a Woman Who Had Been Delivered Formerly by
      Craniotomy: Child Alive.

PMID- 29648362
TI  - Monthly Retrospect of Obstetrics and Gynaecology.

PMID- 29648364
TI  - Occasional Periscope of Surgery and Surgical Pathology.

PMID- 29648363
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29648365
TI  - A New Source of Quinine.

PMID- 29648366
TI  - Meetings of Societies.

PMID- 29648367
TI  - Subjective Symptoms in Eye Diseases.

PMID- 29648368
TI  - Report of the Royal Maternity and Simpson Memorial Hospital for the Quarter
      Ending 31st July 1881.

PMID- 29648369
TI  - Glass as a Cover for Dissecting Tables.

PMID- 29648370
TI  - A Medical Song from "Patience".

PMID- 29648372
TI  - Germs, Busy Germs.

PMID- 29648371
TI  - Statistics of the Inebriates' Home, Long Island.

PMID- 29648373
TI  - Medical Notes from Ceylon.

PMID- 29648374
TI  - Occasional Periscope of Dermatology.

PMID- 29648375
TI  - Delivery by the Breech through a Greatly Narrowed, Flat, Rachitic Pelvis.

PMID- 29648376
TI  - Monthly Retrospect of Obstetrics and Gynaecology.

PMID- 29648377
TI  - On the Actions and Uses of Citrate of Caffein as a Diuretic.

PMID- 29648380
TI  - On Nephrotomy.

PMID- 29648379
TI  - On a Case of Bilateral Paralysis of the Vocal Cords, with Special Reference to
      Diagnosis: Being Portion of a Clinical Lecture Delivered in the Western Infirmary
      of Glasgow, 25th March 1881.

PMID- 29648378
TI  - An Improved Method of Treating Uterine Displacements.

PMID- 29648381
TI  - Periscope of Ophthalmology.

PMID- 29648382
TI  - Retro-Pharyngeal Abscess in an Infant; Sudden Death by Haemorrhage.

PMID- 29648383
TI  - Translation of a Few Remarks Made at Professor Nussbaum's Clinic.

PMID- 29648385
TI  - Meetings of Societies.

PMID- 29648384
TI  - Two Cases of Puerperal Haematocele.

PMID- 29648386
TI  - Fibroid Tumour of the Uterus Complicating Labour: Delivery with Forceps.

PMID- 29648387
TI  - Periscope of Otology.

PMID- 29648388
TI  - Monthly Report on the Progress of Therapeutics.

PMID- 29648389
TI  - Clinical Remarks on Cases of Hydrocele.

PMID- 29648390
TI  - The Basis of Temperament.

PMID- 29648391
TI  - Footnotes to Medical History.

PMID- 29648392
TI  - Simplification of Blood Examination.

PMID- 29648393
TI  - Studies on Stored Blood: VIII. The Effect of Transfusion on Capillary Resistance.
      A Preliminary Note.

PMID- 29648394
TI  - The Value of Tracheo-Bronchoscopy and OEsophagoscopy in Diagnosis and Treatment.

PMID- 29648395
TI  - Some Observations on Calcium Requirement Standards.

PMID- 29648396
TI  - The Effect of War-Time Conditions on the Administration of the Tuberculosis
      Service.

PMID- 29648397
TI  - Glycosuria in Pregnancy as a Predisposing Cause of Vaginal Thrush; with Special
      Reference to Its Importance in the Treatment of This Condition.
AB  - Introduction: Attention is drawn to the fact that pregnancy and glycosuria are
      recognised to be predisposing factors in the causation of vaginal thrush.
      Confusion exists, however, as to the exact nature of the glycosuria associated
      with pregnancy. The critical and often serious glycosuria of diabetes mellitus in
      pregnant women is contrasted with the mild, transient and often symptomless
      glycosuria of pregnancy. The importance of a full understanding of this subject
      lies in this, that the treatment of the patient, with or without insulin, depends
      on it. Part I A Review of our Knowledge of the Glycosuria of Pregnancy: The
      glycosuria of diabetes mellitus is not discussed, but attention is directed only
      to the transient glycosuria of pregnancy. Three rather ill-defined types are
      described: (1) early alimentary glycosuria; (2) renal glycosuria; (3) late
      alimentary glycosuria. The changes in the concentration of glucose in the blood
      and urine of groups of pregnant women when starved and later fed with a known
      quantity of glucose are narrated and compared with the changes in the blood and
      urine of non-pregnant women treated in the same way. An attempt is made to assess
      the incidence of glycosuria among pregnant women living on an ordinary diet. Very
      different estimates by a number of authorities are referred to and are explained,
      in part at least, as due to the time, in relation to a meal, when a sample of
      urine is collected and examined. The character, the quality and amount of the
      meal, as well as the method of detecting the glucose affects the finding, for the
      glycosuria of pregnancy is frequently intermittent. The conclusion is arrived at
      that from 20 to 30 per cent. of women during some part of their pregnancy excrete
      appreciable quantities of glucose in their urine. Part II Discusses the
      Relationship between Glycosuria and Vaginal Thrush and records the Examination
      and Treatment of a Small Number of Patients suffering from that Disease:
      Glycosuria is found to be present in all cases of vaginal thrush if suitable
      arrangements are made to collect and examine samples of urine. The avidity or
      predilection of Oidium albicans for moist acid surfaces soiled with glucose is
      referred to. The possibility that the blastospores of that fungus, which are
      produced in enormous numbers in infected persons, may be dispersed in the air of
      hospital wards containing cases of vaginal thrush is commented upon.The
      examination of the blood and urine while the patient is starving and after a feed
      of 50 grams of glucose in a small series of cases of vaginal thrush is recorded.
      The treatment of four cases as examples is detailed.The general conclusion is
      arrived at, on the basis of the established facts, that a well-balanced diet,
      with adequate vitamin content, must be regarded as an essential part of the
      treatment of vaginal thrush, in addition to the local application of antiseptics
      such as gentian violet or iodine.Careful and frequent examinations of the urine
      for the presence of sugar in samples collected after the main meal of the day and
      during the later stages of the pregnancy, and the correction of errors of diet
      revealed in this way, are prophylactic measures against thrush infection of the
      vagina of pregnant women.

PMID- 29648398
TI  - Progress in the Treatment of Malignant Disease.

PMID- 29648399
TI  - Observations on Tuberculosis of the Larynx.

PMID- 29648400
TI  - The Changing Heart Murmurs of Acute Rheumatism.

PMID- 29648401
TI  - Fibrositis Treated with Vitamin E.

PMID- 29648403
TI  - Intertrigo Treated with Tannic Acid and Brilliant Green.

PMID- 29648402
TI  - Three Old Hospital Dietaries.

PMID- 29648404
TI  - Biopsy of the Sternal Bone Marrow as a Diagnostic Procedure.

PMID- 29648405
TI  - Acute Rheumatism and Trauma.

PMID- 29648406
TI  - The Significance of Fear.

PMID- 29648407
TI  - The Significance of Dilated Intracutaneous Veins on the Chest Wall.

PMID- 29648408
TI  - A Lingual Thyroid: Myxoedema Following Its Removal.

PMID- 29648410
TI  - Surgical Organisation in Air Raids.

PMID- 29648409
TI  - Gaucher's Disease: Report of Two Unrelated Cases.

PMID- 29648411
TI  - Wound Infection and Accidental Wounds : The Antiseptic Eras-Yesterday and To-Day.

PMID- 29648412
TI  - Injuries from Projectiles.

PMID- 29648413
TI  - Joint consensus on abdominal robotic surgery and anesthesia from a task force of
      the SIAARTI and SIC.
AB  - Minimally invasive surgical procedures have revolutionized the world of surgery
      in the past decades. While laparoscopy, the first minimally invasive surgical
      technique to be developed, is widely used and has been addressed by several
      guidelines and recommendations, the implementation of robotic-assisted surgery is
      still hindered by the lack of consensus documents that support healthcare
      professionals in the management of this novel surgical procedure. Here we
      summarize the available evidence and provide expert opinion aimed at improving
      the implementation and resolution of issues derived from robotic abdominal
      surgery procedures. A joint task force of Italian surgeons, anesthesiologists and
      clinical epidemiologists reviewed the available evidence on robotic abdominal
      surgery. Recommendations were graded according to the strength of evidence.
      Statements and recommendations are provided for general issues regarding robotic
      abdominal surgery, operating theatre organization, preoperative patient
      assessment and preparation, intraoperative management, and postoperative
      procedures and discharge. The consensus document provides evidence-based
      recommendations and expert statements aimed at improving the implementation and
      management of robotic abdominal surgery.

PMID- 29648414
TI  - Assessment of left ventricular ejection fraction in critically ill patients at
      the time of speckle tracking echocardiography: intensivists in training for
      echocardiography versus experienced operators.
AB  - BACKGROUND: The biplane Simpson's method is considered the gold standard to
      assess and monitor left ventricular (LV) ejection fraction (EF) in critically ill
      patients. Recently, a new semi-automatic technique based on speckle tracking
      echocardiography called "Auto-EF" has been introduced. We compared LVEF values
      obtained with biplane Simpson's method and Auto-EF by two groups of operators:
      trainee echocardiography intensivists and experienced echocardiographers.
      METHODS: A standard transthoracic echocardiography was performed on 37 patients.
      According to image quality 29 patients were selected. Each inexperienced and
      experienced operator executed an off-line analysis using both Simpson's method
      and Auto-EF. LVEF obtained by the two groups of operators were then compared.
      RESULTS: EF values assessed with Simpson's method showed a moderate correlation
      (r=0.70, P<0.01) between inexperienced and experienced operators. The Bland
      Altman analysis showed a mean bias of 0.3% with limits of agreement (LoA) from 
      24.4 to +25.1%. Values obtained with Auto-EF showed a good correlation (r=0.94,
      P<0.01) with a mean bias of 0.2% and LoA from -10.1 to +10.4%. CONCLUSIONS: Due
      to its semiautomatic nature, for inexpert operators Auto-EF seems more
      reproducible than the traditional Simpson's method for monitoring left
      ventricular function in critically ill patients.

PMID- 29648415
TI  - Management of abdominal compartment syndrome during extracorporeal membrane
      oxygenation: water-assisted colonoscopy as early emergency treatment.

PMID- 29648416
TI  - Hemodynamic assessment in 2018: back to pathophysiological approach.

PMID- 29648417
TI  - The influence of gabapentin on postoperative outcome in obese patients.

PMID- 29648418
TI  - Preparation of Quantum Dots Hydrogel Nanocomposites with Improved Cytotoxicity.
AB  - Nanocomposites are materials with unique properties and a wide range of
      applications. The combination of different nanostructures with traditional
      materials gives a variety of possibilities that should be analyzed. Especially,
      functional fluorescent semiconductor quantum dots (QDs) embedded in polymeric
      matrices have shown promising fluorescence and biocompatibility properties. These
      hybrid materials can be used in medical applications such as biodiagnostic and
      bioimaging. In this study, two hydrogels, one of polyethylene glycol diacrylate
      (PEGDA) and other of polyacrylamide (PAAm), were prepared with quantum dots of
      CdTe (4 nm of diameter) and characterized. The aim of this research was to
      analyze the optical properties of the nanocomposites and their cell viability.
      QDs nanocomposites were fabricated by a free radical polymerization process. The
      optical studies showed that the nanocomposites have well defined properties of
      fluorescence. To study the biocompatibility of the nanocomposites, metastatic
      B16f10 cell line were used and MTT assay was performed. The nanocomposites had a
      significant improved cell viability compared with QDs solutions.

PMID- 29648419
TI  - Influence of Incubation Conditions on the Nanoparticles Toxicity Based on Seed
      Germination and Bacterial Bioluminescence.
AB  - The effects of the modified incubation conditions of a conventional bioassay on
      the toxicity of partially soluble nanoparticles (NPs) were evaluated based on the
      activity of seed germination and bacterial bioluminescence. Different levels of
      toxicity were observed for seed germination (CuO > ZnO > NiO) and bacterial
      bioluminescence (ZnO > CuO > NiO). The NP inhibition of seed germination
      increased strongly under modified incubation conditions: sample volume from 5 mL
      to 10 mL, shaking from none to 70 rpm, and working vessel from a Petri dish (+/-
      filter paper) to an Erlenmeyer flask (no filter paper). In the case of seed
      germination, the toxicity levels of NPs under the modified conditions were 1.26
      to 8.49 times higher than the conventional method according to the type of NPs
      and modified conditions (p-values < 0.05). No significant differences in
      bacterial bioluminescence were observed between conventional (130 rpm) and
      modified (160 rpm) conditions. These findings show that for an accurate
      assessment of partially soluble NPs toxicity in ecosystems, the conventional
      bioassay method, which is designed for soluble chemicals, needs to be performed
      under modified conditions because of their insolubility.

PMID- 29648420
TI  - Prenatal Exposure to DDT and Pyrethroids for Malaria Control and Child
      Neurodevelopment: The VHEMBE Cohort, South Africa.
AB  - BACKGROUND: Although indoor residual spraying (IRS) with
      dichlorodiphenyltrichloroethane (DDT) and pyrethroids effectively controls
      malaria, it potentially increases human exposure to these insecticides. Previous
      studies suggest that prenatal exposure to these insecticides may impact human
      neurodevelopment. OBJECTIVES: We aimed to estimate the effects of maternal
      insecticide exposure and neurodevelopment of toddlers living in a malaria-endemic
      region currently using IRS. METHODS: The Venda Health Examination of Mothers,
      Babies and their Environment (VHEMBE) is a birth cohort of 752 mother-child pairs
      in Limpopo, South Africa. We measured maternal exposure to DDT and its breakdown
      product, dichlorodiphenyldichloroethylene (DDE), in maternal serum, and measured
      pyrethroid metabolites in maternal urine. We assessed children's neurodevelopment
      at 1 and 2 y of age using the Bayley Scales of Infant Development, third edition
      (BSID-III), and examined associations with maternal exposure. RESULTS: DDT and
      DDE were not associated with significantly lower scores for any BSID-III scale.
      In contrast, each 10-fold increase in cis-DCCA, trans-DCCA, and 3-phenoxybenzoic
      acid were associated, respectively, with a -0.63 (95% CI: -1.14, -0.12), -0.48
      (95% CI: -0.92, -0.05), and -0.58 (-1.11, -0.06) decrement in Social-Emotional
      scores at 1 y of age. In addition, each 10-fold increase in maternal cis-DBCA
      levels was associated with significant decrements at 2 y of age in Language
      Composite scores and Expressive Communication scores [beta=-1.74 (95% CI: -3.34, 
      0.13) and beta=-0.40 (95% CI: -0.77, -0.04), respectively, for a 10-fold
      increase]. Significant differences by sex were estimated for pyrethroid
      metabolites and motor function scores at 2 y of age, with higher scores for boys
      and lower scores for girls. CONCLUSIONS: Prenatal exposure to pyrethroids may be
      associated at 1 y of age with poorer social-emotional development. At 2 y of age,
      poorer language development was observed with higher prenatal pyrethroid levels.
      Considering the widespread use of pyrethroids, these findings deserve further
      investigation. https://doi.org/10.1289/EHP2129.

PMID- 29648421
TI  - Rice Bran Extract Inhibits TMEM16A-Involved Activity in the Neonatal Rat Cochlea.
AB  - TMEM16A is a Ca2+-activated Cl- channel found in secretory glands, GI and
      respiratory tracts, and sensory organs, playing a major physiological role in
      fluid secretion, autonomous GI motility, and sensory transduction. In addition,
      overexpression of TMEM16A has been associated with cancer cell proliferation and
      invasion. Suppression of upregulated TMEM16A has been proposed as an effective
      anti-cancer strategy. While searching for a potential TMEM16A inhibitor,
      components of rice bran attracted our attention due to their anti-cancer
      potential in colon cancer cells, a type of cells known to overexpressing TMEM16A.
      Here, it was tested whether rice bran extract exhibits anti-TMEM16A activity.
      Rice bran extract was tested in the neonatal rat cochlear tissues where TMEM16A
      involved spontaneous activity is generated as a part of normal development of the
      auditory pathway. Rice bran extract readily inhibited the TMEM16A-involved
      activity in the cochlear tissues and the effect was reversible upon washout.
      Taken together, rice bran extract appears to contain a putative TMEM16A inhibitor
      and the rice byproduct might serve as a source of a new anti-cancer agent.

PMID- 29648422
TI  - Contralateral Cervical Nerve Transfer for Arm Paralysis.

PMID- 29648423
TI  - Cardiac Arrest during Competitive Sports.

PMID- 29648424
TI  - Cardiac Arrest during Competitive Sports.

PMID- 29648425
TI  - Cardiac Arrest during Competitive Sports.

PMID- 29648426
TI  - Cardiac Arrest during Competitive Sports.

PMID- 29648427
TI  - Cardiac Arrest during Competitive Sports.

PMID- 29648428
TI  - Cardiac Arrest during Competitive Sports.

PMID- 29648429
TI  - Neuroprotective Effects of the Nanoparticles of Zinc Sapogenin from Seeds of
      Camellia oleifera.
AB  - The sapogenin isolated from seeds of Camellia oleifera shows central effects in
      our previous research. Aiming to improve its neuroprotective effects, we
      synthesize the zinc-sapogenin complex, which has been found with the nanoparticle
      characters and neuroprotective effects. Its structure is deduced as
      sapogenin:zinc:water (3:1:1) by ultraviolet spectra, infrared spectra, element
      analysis, and thermogravimetric analysis. The average size of zinc-sapogenin is
      115 nm with plane circular shape by measurement of particle analyzer and scanning
      electron microscope. The nanoparticle improves DPPH radical scavenging activity
      due to the enhancement of electron transfer among atoms through the linkage of
      zinc with the sapogenin. Intraperitoneal injection of zinc-sapogenin reduced mice
      behavioral disorder and neuron damage induced by neurotoxicity of rotenone,
      increased antioxidative ability and promoted the neurotransmitters of dopamine
      and acetylcholine in mice brain. Zinc strengthens stability and effects of the
      sapogenin, and it is a superior candidate of drugs for neuroprotection without
      accumulation in brain.

PMID- 29648430
TI  - Evaluation of Versatile CdS Nanomaterials Based Liquid Crystals Switchable
      Device.
AB  - Novel synthesis and properties of versatile CdS nanostructures (e.g., Nano-brush,
      nano-cube, nanosphere) dispersed liquid crystals application in chemical friendly
      medium exploring this article. Most recent studies, CdS nano-wire brush with the
      stacking fault structures were hydrothermally synthesized through a dissolution
      recrystallization approach in concentrated ammonia solvent in one step solution,
      for the first time. Those structures-property relations with respect to
      ferroelectric hydrogen-bonded liquid-crystalline complex (HBLC; AC + 5BAO)
      controlled and efficient formation of surface relief nanostructures. A successful
      attempt has been made to form hydrogen bonding between CdS nanostructures and
      supramolecular LC with p-n-alkyloxy benzoic acids (n-OBA). The formation of an
      inter-H-bond is evinced through FTIR study, as well as Gaussian simulation also
      ensures complete formation of intermolecular hydrogen bond optimized geometry. In
      contrast, a new sensitive response of smectic G ordering observed in this series
      is investigated by constructing a phase diagram obtained from two binary mixtures
      of CdS nanostructures influenced by homogeneous liquid crystals. Temperature
      dependent dielectric relaxation, tilt angle, electro-optical switching
      measurements allow for monitoring very unique and useful behavior in that the
      polarization of the emission from the semiconductor nanostructures can be
      controlled by an external bias. It reveals electrically tunable interaction of
      the composites may allow for engineering of practical electro-optic switchable
      device.

PMID- 29648431
TI  - Post-Synthesis Separation and Storage of Zero-Valent Iron Nanoparticles.
AB  - Zero-valent iron (ZVI) nanoparticles are susceptible to oxidation and are
      therefore sensitive to postsynthesis processing, including both separation and
      storage techniques. Two separation methods, centrifugation and magnetic
      separation, were evaluated in this study. Nanoparticle stability during storage
      in ethanol-water solutions was also studied, and the influence of both water and
      aeration on nanoparticle oxidation was determined. Nanoparticle morphology and
      extent of oxidation were analyzed with electron microscopy, elemental analysis,
      zeta potential, and X-ray photoelectron spectroscopy. Microscopy results suggest
      that the separation method used affects the extent of stabilizer that remains
      adsorbed to the nanoparticles, but both separation methods result in minimal
      oxidation of the nanoparticles. However, the addition of aerated water to
      nanoparticle-ethanol storage solutions caused nanoparticle oxidation; an increase
      in the volume fraction of water added caused a linear increase in oxygen content
      based on elemental analysis of nanoparticle samples. X-ray photoelectron
      spectroscopy results suggest that organic stabilizer is incorporated into the
      nanoparticle structure as oxidation occurs.

PMID- 29648433
TI  - Longitudinal Water Proton Relaxivity and In Vivo T1 MR Images of Mixed
      Zn(II)/Gd(III) Oxide Nanoparticles.
AB  - Mixed Zn(II)/Gd(III) oxide nanoparticles (~8 mole%Zn) with d(avg) of 2.1 nm were
      synthesized. The D-glucuronic acid coated Zn(II)/Gd(III) oxide nanoparticles
      showed a longitudinal water proton relaxivity (r1) of 12.3 s-1mM-1 with r2/r1 =
      1.1, corresponding to an ideal condition for T1 MRI contrast agent. We attribute
      this to reduced magnetization of the mixed nanoparticles owing to non-magnetic Zn
      in the nanoparticles. Their effectiveness as a T1 MRI contrast agent was
      confirmed by acquiring In Vivo T1 MR images of a mouse after intravenous
      injection.

PMID- 29648434
TI  - Tip-Enhanced Photoinduced Electron Transfer and Ionization on Vertical Silicon
      Nanowires.
AB  - Nanostructured semiconductors are one of the most potent candidates for matrix
      free laser desorption/ionization mass spectrometric (LDI-MS) analysis of low
      molecular-weight molecules. Herein, the enhanced photoinduced electron transfer
      and LDI on the tip of a vertical silicon nanowire (SiNW) array were investigated.
      Theoretical simulation and LDI detection of indigo and isatin molecules in
      negative ion mode revealed that the electric field can be enhanced on the tip end
      of SiNWs, thereby promoting the energy and electron transfer to the analytes
      adsorbed on the tip of SiNWs. On the basis of this finding, a tip-contact
      sampling method coupled with LDI-MS detection was established. In this strategy,
      the tip of SiNWs can be regarded as microextraction heads for the sampling of
      molecules when they come in contact with analytes. Impression of skin, tissue,
      and pericarp on the vertical SiNW array can effectively transfer endogenous
      metabolites or exogenous substances onto the tip. Upon laser irradiation, the
      adsorbed molecules on the SiNW tip can be efficiently ionized and detected in
      negative ion mode because of the tip-enhanced electron transfer and LDI effect.
      We believe this work may significantly expand the application of LDI-MS in
      various fields.

PMID- 29648435
TI  - Fluoroethylene Carbonate-Based Electrolyte with 1 M Sodium
      Bis(fluorosulfonyl)imide Enables High-Performance Sodium Metal Electrodes.
AB  - Sodium (Na) metal anodes with stable electrochemical cycling have attracted
      widespread attention because of their highest specific capacity and lowest
      potential among anode materials for Na batteries. The main challenges associated
      with Na metal anodes are dendritic formation and the low density of deposited Na
      during electrochemical plating. Here, we demonstrate a fluoroethylene carbonate
      (FEC)-based electrolyte with 1 M sodium bis(fluorosulfonyl)imide (NaFSI) salt for
      the stable and dense deposition of the Na metal during electrochemical cycling.
      The novel electrolyte combination developed here circumvents the dendritic Na
      deposition that is one of the primary concerns for battery safety and constructs
      the uniform ionic interlayer achieving highly reversible Na plating/stripping
      reactions. The FEC-NaFSI constructs the mechanically strong and ion-permeable
      interlayer containing NaF and ionic compounds such as Na2CO3 and sodium
      alkylcarbonates.

PMID- 29648436
TI  - Toward High-Performance Lithium-Sulfur Batteries: Upcycling of LDPE Plastic into
      Sulfonated Carbon Scaffold via Microwave-Promoted Sulfonation.
AB  - Lithium-sulfur batteries were intensively explored during the last few decades as
      next-generation batteries owing to their high energy density (2600 Wh kg-1) and
      effective cost benefit. However, systemic challenges, mainly associated with
      polysulfide shuttling effect and low Coulombic efficiency, plague the practical
      utilization of sulfur cathode electrodes in the battery market. To address the
      aforementioned issues, many approaches have been investigated by tailoring the
      surface characteristics and porosities of carbon scaffold. In this study, we
      first present an effective strategy of preparing porous sulfonated carbon (PSC)
      from low-density polyethylene (LDPE) plastic via microwave-promoted sulfonation.
      Microwave process not only boosts the sulfonation reaction of LDPE but also
      induces huge amounts of pores within the sulfonated LDPE plastic. When a PSC
      layer was utilized as an interlayer in lithium-sulfur batteries, the sulfur
      cathode delivered an improved capacity of 776 mAh g-1 at 0.5C and an excellent
      cycle retention of 79% over 200 cycles. These are mainly attributed to two
      materialistic benefits of PSC: (a) porous structure with high surface area and
      (b) negatively charged conductive scaffold. These two characteristics not only
      facilitate the improved electrochemical kinetics but also effectively block the
      diffusion of polysulfides via Coulomb interaction.

PMID- 29648437
TI  - pH-Responsive Magnetic Mesoporous Silica-Based Nanoplatform for Synergistic
      Photodynamic Therapy/Chemotherapy.
AB  - By overcoming drug resistance and subsequently enhancing the treatment, the
      combination therapy of photodynamic therapy (PDT) and chemotherapy has promising
      potential for cancer treatment. However, the major challenge is how to establish
      an advanced nanoplatform that can be efficiently guided to tumor sites and can
      then stably release both chemotherapy drugs and a photosensitizer simultaneously
      and precisely. In this study, which considered the possibility and targeting
      efficiency of a magnetic targeting strategy, a novel Fe3O4@mSiO2(DOX)@HSA(Ce6)
      nanoplatform was successfully built; this platform could be employed as an
      efficient synergistic antitumor nanoplatform with magnetic guidance for highly
      specific targeting and retention. Doxorubicin (DOX) molecules were loaded into
      mesoporous silica with high loading capability, and the mesoporous channels were
      blocked by a polydopamine coating. Human serum albumin (HSA) was conjugated to
      the outer surface to increase the biocompatibility and blood circulation time, as
      well as to provide a vehicle for loading photosensitizer chlorin e6 (Ce6). The
      sustained release of DOX under acidic conditions and the PDT induced by red light
      exerted a synergistic inhibitory effect on glioma cells. Our experiments
      demonstrated that the pH-responsive Fe3O4@mSiO2(DOX)@HSA(Ce6) nanoplatform was
      guided to the tumor region by magnetic targeting and that the nanoplatform
      suppressed glioma tumor growth efficiently, implying that the system is a highly
      promising photodynamic therapy/chemotherapy combination nanoplatform with
      synergistic effects for cancer treatment.

PMID- 29648438
TI  - A Nanocomposite Hydrogel with Potent and Broad-Spectrum Antibacterial Activity.
AB  - Local bacterial infection is a challenging task and still remains a serious
      threat to human health in clinics. Systemic administration of antibiotics has
      only short-term antibacterial activity and usually causes adverse effects and
      bacterial resistance. A bioadhesive hydrogel with broad-spectrum and on-demand
      antibiotic activity is highly desirable. Here, we designed a pH-responsive
      nanocomposite hydrogel via a Schiff base linkage between oxidized polysaccharides
      and cationic dendrimers encapsulated with silver nanoparticles. The antibacterial
      components, both the cationic dendrimers and silver species, could be released in
      response to the acidity generated by growing bacteria. The released cationic
      polymer and silver exhibited a synergistic effect in antibacterial activity, and
      thus, the nanocomposite hydrogel showed potent antibacterial activity against
      both Gram-negative ( Escherichia coli and Pseudomonas aeruginosa) and Gram
      positive bacteria ( Staphylococcus epidermidis and Staphylococcus aureus). The
      gel showed superior in vivo antibacterial efficacy against S. aureus infection
      compared with a commercial silver hydrogel at the same silver concentration. In
      addition, no obvious hemolytic toxicity, cytotoxicity, and tissue and biochemical
      toxicity were observed for the antibacterial hydrogel after incubation with cells
      or implantation. This study provides a facile and promising strategy to develop
      smart hydrogels to treat local bacterial infections.

PMID- 29648439
TI  - Development and Synthesis of DNA-Encoded Benzimidazole Library.
AB  - Encoded library technology (ELT) is an effective approach to the discovery of
      novel small-molecule ligands for biological targets. A key factor for the success
      of the technology is the chemical diversity of the libraries. Here we report the
      development of DNA-conjugated benzimidazoles. Using 4-fluoro-3-nitrobenzoic acid
      as a key synthon, we synthesized a 320 million-member DNA-encoded benzimidazole
      library using Fmoc-protected amino acids, amines and aldehydes as diversity
      elements. Affinity selection of the library led to the discovery of a novel,
      potent and specific antagonist of the NK3 receptor.

PMID- 29648440
TI  - Spontaneous Transport of Single-Stranded DNA through Graphene-MoS2
      Heterostructure Nanopores.
AB  - The effective transport of a single-stranded DNA (ssDNA) molecule through a solid
      state nanopore is essential to the future success of high-throughput and low-cost
      DNA sequencing. Compatible with current electric sensing technologies, here, we
      propose and demonstrate by molecular dynamics simulations the ssDNA transport
      through a quasi-two-dimensional nanopore in a heterostructure stacked together
      with different 2D materials, such as graphene and molybdenum disulfide (MoS2).
      Due to different chemical potentials, U, of DNA bases on different 2D materials,
      it is energetically favorable for a ssDNA molecule to move from the low- U MoS2
      surface to the high- U graphene surface through a nanopore. With the proper
      attraction between the negatively charged phosphate group in each nucleotide and
      the positively charged Mo atoms exposed on the pore surface, the ssDNA molecule
      can be temporarily seized and released thereafter through a thermal activation,
      that is, a slow and possible nucleotide-by-nucleotide transport. A theoretical
      formulation is then developed for the free energy of the ssDNA transiting a
      heterostructure nanopore to properly characterize the non-equilibrium stick-slip
      like motion of a ssDNA molecule.

PMID- 29648441
TI  - Biocompatible Polymers Modified with d-Octaarginine as an Absorption Enhancer for
      Nasal Peptide Delivery.
AB  - Peptide and protein drugs, which are categorized as biologics, exhibit poor
      membrane permeability. This pharmacokinetic disadvantage has largely restricted
      the development of noninvasive dosage forms of biologics that deliver into
      systemic circulation. We have been investigating the potential use of cell
      penetrating peptide-linked polymers as a novel absorption enhancer to overcome
      this challenge. Since our previous study revealed that biocompatible poly( N
      vinylacetamide- co-acrylic acid) modified with d-octaarginine, a typical cell
      penetrating peptide, enhanced in vitro permeation of biomolecules such as plasmid
      DNA and bovine serum albumin through cell membranes, the present study evaluated
      whether the polymers enhanced in vivo absorption of biologics applied on the
      mucosa. Mouse experiments demonstrated that d-octaarginine-linked polymers
      drastically enhanced nasal absorption of exendin-4, whose injection is clinically
      used. The mean bioavailability was 20% relative to subcutaneous administration,
      even though it fell short of 1% when exendin-4 alone was administered nasally.
      The absorption-enhancing function of the polymers was superior to that of sodium
      caprate and sodium N-(8-(2-hydroxybenzoyl)amino) caprylate, which have been used
      for humans as an absorption enhancer. In vitro experiments using several
      biologics with different characteristics revealed that biologics interacted with
      d-octaarginine-linked polymers and were taken up into cells when incubated with
      the polymers. The interaction and cellular uptake were enhanced as molecular
      weights of the biologics increased; however, their charge-dependent in vitro
      performance was not clearly observed. The current data suggested that biologics
      formulated with our polymers became an alternative to their conventional invasive
      parenteral formulations.

PMID- 29648442
TI  - NIR-to-Red Upconversion Nanoparticles with Minimized Heating Effect for
      Synchronous Multidrug Resistance Tumor Imaging and Therapy.
AB  - Lanthanide-doped upconversion nanoparticles (UCNPs), especially the 808 nm
      activated UCNPs, are promising imaging agents for biological applications because
      of their minimal tissue overheating effects and low autofluorescence background.
      Optimizing the emission peaks located in the "biological window (600-1100 nm)" is
      of vital importance to obtain the maximum penetration depth and intense deep
      tissue imaging. On the other hand, because of the widely existing multidrug
      resistance (MDR) of tumor cells, traditional tumor chemotherapy often fails to
      achieve the desired effect. Herein, a new type of 808 nm excited pure red
      luminescence core-shell Nd3+-sensitized NaY(Mn)F4:Yb/Er@NaYbF4:Nd UCNPs (CSUCNPs)
      was designed and synthesized for deep tissue imaging and MDR tumor diagnosis with
      a minimized heating effect. In the meanwhile, d-alpha-tocopherol polyethylene
      glycol 1000 succinate (TPGS) coating was introduced to endow CSUCNPs with
      capabilities of drug loading and overcoming MDR. The in vitro cytotoxicity test
      revealed that CSUCNPs-TPGS-doxorubicin (D-CSUCT) had excellent MDR cancer cell
      killing efficacy. The in vivo test showed that D-CSUCT can target the tumor site
      by enhanced retention effect, and the intense luminescent signals from the tumor
      site in the deep tissue were detected. Generally, this work shows D-CSUCT can
      overcome the MDR effect, diagnose the tumor, inhibit tumor growth, and induce
      tumor cells necrosis and apoptosis, without causing damage to major organs and
      other side effects. Overall, the study demonstrates the conjugation of red
      emitted UCNPs with a minimized heating effect and that the anti-MDR carrier is
      highly promising for developing multifunctional theranostic system with effective
      simultaneous diagnosis and for multidrug-resistant tumor treatment.

PMID- 29648443
TI  - Shedding Light on the Molecular Pathology of Amyloid Plaques in Transgenic
      Alzheimer's Disease Mice Using Multimodal MALDI Imaging Mass Spectrometry.
AB  - Senile plaques formed by aggregated amyloid beta peptides are one of the major
      pathological hallmarks of Alzheimer's disease (AD) which have been suggested to
      be the primary influence triggering the AD pathogenesis and the rest of the
      disease process. However, neurotoxic Abeta aggregation and progression are
      associated with a wide range of enigmatic biochemical, biophysical and genetic
      processes. MALDI imaging mass spectrometry (IMS) is a label-free method to
      elucidate the spatial distribution patterns of intact molecules in biological
      tissue sections. In this communication, we utilized multimodal MALDI-IMS analysis
      on 18 month old transgenic AD mice (tgArcSwe) brain tissue sections to enhance
      molecular information correlated to individual amyloid aggregates on the very
      same tissue section. Dual polarity MALDI-IMS analysis of lipids on the same pixel
      points revealed high throughput lipid molecular information including
      sphingolipids, phospholipids, and lysophospholipids which can be correlated to
      the ion images of individual amyloid beta peptide isoforms at high spatial
      resolutions (10 MUm). Further, multivariate image analysis was applied in order
      to probe the multimodal MALDI-IMS data in an unbiased way which verified the
      correlative accumulations of lipid species with dual polarity and Abeta peptides.
      This was followed by the lipid fragmentation obtained directly on plaque
      aggregates at higher laser pulse energies which provided tandem MS information
      useful for structural elucidation of several lipid species. Majority of the
      amyloid plaque-associated alterations of lipid species are for the first time
      reported here. The significance of this technique is that it allows correlating
      the biological discussion of all detected plaque-associated molecules to the very
      same individual amyloid plaques which can give novel insights into the molecular
      pathology of even a single amyloid plaque microenvironment in a specific brain
      region. Therefore, this allowed us to interpret the possible roles of lipids and
      amyloid peptides in amyloid plaque-associated pathological events such as focal
      demyelination, autophagic/lysosomal dysfunction, astrogliosis, inflammation,
      oxidative stress, and cell death.

PMID- 29648444
TI  - Headspace-Sampling Paper-Based Analytical Device for Colorimetric/Surface
      Enhanced Raman Scattering Dual Sensing of Sulfur Dioxide in Wine.
AB  - This study demonstrates a novel strategy for colorimetric/surface-enhanced Raman
      scattering (SERS) dual-mode sensing of sulfur dioxide (SO2) by coupling headspace
      sampling (HS) with paper-based analytical device (PAD). The smart and
      multifunctional PAD is fabricated with a vacuum filtration method in which 4
      mercaptopyridine (Mpy)-modified gold nanorods (GNRs)-reduced graphene oxide (rGO)
      hybrids (rGO/MPy-GNRs), anhydrous methanol, and starch-iodine complex are
      immobilized into cellulose-based filter papers. The resultant PAD exhibits a deep
      blue color with a strong absorption peak at 600 nm due to the formation of an
      intermolecular charge-transfer complex between starch and iodine. However, the
      addition of SO2 induces the Karl Fischer reaction, resulting in the decrease of
      color and increase of SERS signals. Therefore, the PAD can be used not only as a
      naked-eye indicator of SO2 changed from blue to colorless but also as a highly
      sensitive SERS substrates because of the SO2-triggered conversion of Mpy to
      pyridine methyl sulfate on the GNRs. A distinguishable change in the color was
      observed at a SO2 concentration of 5 MUM by the naked eye, and a detection limit
      as low as 1.45 MUM was obtained by virtue of UV-vis spectroscopy. The PAD-based
      SERS method is effective over a wide range of concentrations (1 MUM to 2000 MUM)
      for SO2, and the detection limit for SO2 is found to be 1 MUM. The HS-PAD based
      colorimetric/SERS method is applied for the determination of SO2 in wine, and the
      detection results match well with those obtained from the traditional Monier
      Williams method. This study not only offers a new method for on-site monitoring
      of SO2 but also provides a new strategy for designing of paper-based sensing
      platform for a wide range of field-test applications.

PMID- 29648445
TI  - Manipulating Femtoliter to Picoliter Droplets by Pins for Single Cell Analysis
      and Quantitative Biological Assay.
AB  - Herein, we developed an automated and flexible system for performing miniaturized
      liquid-liquid reactions and assays in the femtoliter to picoliter range, by
      combining the contact printing and the droplet-based microfluidics techniques.
      The system mainly consisted of solid pins and an oil-covered hydrophilic
      micropillar array chip fixed on an automated x- y- z translation stage. A novel
      droplet manipulation mode called "dipping-depositing-moving" (DDM) was proposed,
      which was based on the programmable combination of three basic operations,
      dipping liquids and depositing liquids with the solid pins and moving the two
      dimensional oil-covered hydrophilic pillar microchip. With the DDM mode, flexible
      generation and manipulation of small droplets with volumes down to 179 fL could
      be achieved. For overcoming the scale phenomenon specially appeared in picoliter
      scale droplets, we used a design of water moat to protect the femtoliter to
      picoliter droplets from volume loss through the cover oil during the droplet
      generation, manipulation, reaction and assay processes. Moreover, we also
      developed a precise quantitative method, quantitative droplet dilution method, to
      accurately measure the volumes of femtoliter to picoliter droplets. To
      demonstrate its feasibility and adaptability, we applied the present system in
      the determination of kinetics parameter for matrix metalloproteinases (MMP-9) in
      1.81 pL reactors and the measurement the activity of beta-galactosidase in single
      cells (HepG2 cells) in picoliter droplet array. The ultrasmall volumes of the
      droplet reactors avoided the excessive dilution to the reaction solutions and
      enabled the highly sensitive measurement of enzyme activity in the single cell
      level.

PMID- 29648446
TI  - Evans Blue Derivative-Functionalized Gold Nanorods for Photothermal Therapy
      Enhanced Tumor Chemotherapy.
AB  - Chemotherapy is a standard care for cancer management, but the lack of tumor
      targeting and high dose-induced side effects still limit its utility in patients.
      Here, we report a chemotherapy combined with photothermal therapy (PTT) for
      enhanced cancer ablation by functionalization of gold nanorods (GNRs) with a
      novel small molecule named truncated Evans blue (tEB). On the basis of the high
      binding affinity of tEB with albumin, an Abraxane-like nanodrug, human serum
      albumin/hydroxycamptothecin (HSA/HCPT), was further complexed with GNR-tEB. This
      formed an HCPT/HSA/tEB-GNR (HHEG) with excellent biostability and
      biocompatibility. With photoacoustic and fluorescence imaging, we observed HHEG
      tumor targeting, which is mediated by enhanced permeability retention effect. The
      accumulation of HHEG peaked in tumor at 12 h postinjection. Moreover, HHEG can
      effectively ablate tumor growth with laser illumination via chemo/thermal therapy
      after intravenous administration into SCC7 tumor. This combination is much better
      than chemotherapy or PTT alone. Collectively, we constructed a chemo/thermal
      therapy nanostructure based on a tEB-modified GNR for better tumor treatment
      effect. The use of tEB in gold nanoparticles can facilitate many new approaches
      to design hybrid nanoparticles.

PMID- 29648447
TI  - pH-Responsive Nanoscale Covalent Organic Polymers as a Biodegradable Drug Carrier
      for Combined Photodynamic Chemotherapy of Cancer.
AB  - Covalent organic polymers (COPs) are a promising class of cross-linked polymeric
      networks and porous structures composed of covalent organic molecules that
      attract extensive attention. Despite increasing interest in applying COPs for
      applications in nanomedicine, the pH-sensitive COPs that are able to sensitively
      respond to the slightly acidic tumor microenvironment for tumor-specific drug
      delivery and therapy remain to be explored to our best knowledge. Herein, a new
      style of pH-responsive COPs were prepared using acryloyl meso-tetra( p
      hydroxyphenyl) porphine (acryloyl-THPP) to react with 4,4'-trimethylene
      dipiperidine to form the pH-responsive cross-linked biodegradable beta-amino
      esters (BAEs). Amine-modified poly(ethylene glycol) (PEG) was then introduced to
      terminate the reaction and form the PEG shell. The formulated pH-responsive THPP
      BAE-PEG COPs can be utilized to encapsulate anticancer drug doxorubicin (DOX) due
      to their porous structure. Upon intravenous injection, such DOX-loaded COPs show
      a prolonged blood circulation as well as an efficient tumor accumulation. Along
      with the pH-triggered drug release for chemotherapy, the singlet oxygen produced
      by THPP under light exposure for photodynamic therapy would further endow us a
      combined treatment strategy, which offers synergistic antitumor effects in our in
      vivo tumor model experiments. Our study illustrates that COPs fabricated with
      tumor microenvironment responsive linkers may be a promising type of materials
      for applications in cancer nanomedicine.

PMID- 29648448
TI  - Force Field Benchmark of Amino Acids: I. Hydration and Diffusion in Different
      Water Models.
AB  - Thermodynamic and kinetic properties are of critical importance for the
      applicability of computational models to biomolecules such as proteins. Here we
      present an extensive evaluation of the Amber ff99SB-ILDN force field for modeling
      of hydration and diffusion of amino acids with three-site (SPC, SPC/E, SPC/Eb,
      and TIP3P), four-site (TIP4P, TIP4P-Ew, and TIP4P/2005), and five-site (TIP5P and
      TIP5P-Ew) water models. Hydration free energies (HFEs) of neutral amino acid side
      chain analogues have little dependence on the water model, with a root-mean
      square error (RMSE) of ~1 kcal/mol from experimental observations. On the basis
      of the number of interacting sites in the water model, HFEs of charged side
      chains can be putatively classified into three groups, of which the group of
      three-site models lies between those of four- and five-site water models; for
      each group, the water model dependence is greatly eliminated when the solvent
      Galvani potential is considered. Some discrepancies in the location of the first
      hydration peak ( RRDF) in the ion-water radial distribution function between
      experimental and calculated observations were detected, such as a systematic
      underestimation of the acetate (Asp side chain) ion. The RMSE of calculated
      diffusion coefficients of amino acids from experiment increases linearly with the
      increasing diffusion coefficients of the solvent water models at infinite
      dilution. TIP3P has the fastest diffusivity, in line with literature findings,
      while the "FB" and "OPC" water model families as well as TIP4P/2005 perform well,
      within a relative error of 5%, and TIP4P/2005 yields the most accurate estimate
      for the water diffusion coefficient. All of the tested water models overestimate
      amino acid diffusion coefficients by approximately 40% (TIP4P/2005) to 200%
      (TIP3P). Scaling of protein-water interactions with TIP4P/2005 in the Amber
      ff99SBws and ff03ws force fields leads to more negative HFEs but has little
      influence on the diffusion of amino acids. The most recent FF/water combinations
      of ff14SB/OPC3, ff15ipq/SPC/Eb, and fb15/TIP3P-FB do not show obvious
      improvements in accuracy for the tested quantities. These findings here establish
      a benchmark that may aid in the development and improvement of classical force
      fields to accurately model protein dynamics and thermodynamics.

PMID- 29648452
TI  - Slow Auger Relaxation in HgTe Colloidal Quantum Dots.
AB  - The biexciton lifetimes in HgTe colloidal quantum dots are measured as a function
      of particle size. Samples produced by two synthetic methods, leading to partially
      aggregated or well-dispersed particles, exhibit markedly different dynamics. The
      relaxation characteristics of partially aggregated HgTe inhibit reliable
      determinations of the Auger lifetime. In well-dispersed HgTe quantum dots, the
      biexciton lifetime increases approximately linearly with particle volume,
      confirming trends observed in other systems. The extracted Auger coefficient is
      three orders of magnitude smaller than that for bulk HgCdTe materials with
      similar energy gaps. We discuss these findings in the context of understanding
      Auger relaxation in quantum-confined systems and their relevance to mid-infrared
      optoelectronic devices based on HgTe colloidal quantum dots.

PMID- 29648451
TI  - Activation of Periodate by Freezing for the Degradation of Aqueous Organic
      Pollutants.
AB  - A new strategy (i.e., freezing) for the activation of IO4- for the degradation of
      aqueous organic pollutants was developed and investigated. Although the
      degradation of furfuryl alcohol (FFA) by IO4- was negligible in water at 25 
      degrees C, it proceeded rapidly during freezing at -20  degrees C. The rapid
      degradation of FFA during freezing should be ascribed to the freeze concentration
      effect that provides a favorable site (i.e., liquid brine) for the proton-coupled
      degradation process by concentrating IO4-, FFA, and protons. The maximum
      absorption wavelength of cresol red (CR) was changed from 434 nm (monoprotonated
      CR) to 518 nm (diprotonated CR) after freezing, which confirms that the pH of the
      aqueous IO4- solution decreases by freezing. The degradation experiments with
      varying experimental parameters demonstrate that the degradation rate increases
      with increasing IO4- concentration and decreasing pH and freezing temperature.
      The application of the IO4-/freezing system is not restricted to FFA. The
      degradation of four other organic pollutants (i.e., tryptophan, phenol, 4
      chlorophenol, and bisphenol A) by IO4-, which was negligible in water, proceeded
      during freezing. In addition, freezing significantly enhanced the IO4--mediated
      degradation of cimetidine. The outdoor experiments performed on a cold winter
      night show that the IO4-/freezing system for water treatment can be operated
      without external electrical energy.

PMID- 29648449
TI  - Knockout of rapC Improves the Bacillomycin D Yield Based on De Novo Genome
      Sequencing of Bacillus amyloliquefaciens fmbJ.
AB  - Bacillus amyloliquefaciens, a Gram-positive and soil-dwelling bacterium, could
      produce secondary metabolites that suppress plant pathogens. In this study, we
      provided the whole genome sequence results of B. amyloliquefaciens fmbJ, which
      had one circular chromosome of 4 193 344 bp with 4249 genes, 87 tRNA genes, and
      27 rRNA genes. In addition, fmbJ was found to contain several gene clusters of
      antimicrobial lipopeptides (bacillomycin D, surfactin, and fengycin), and
      bacillomycin D homologues were further comprehensively identified. To clarify the
      influence of rapC regulating the synthesis of lipopeptide on the yield of
      bacillomycin D, rapC gene in fmbJ was successfully deleted by the marker-free
      method. Finally, it was found that the deletion of rapC gene in fmbJ
      significantly improved bacillomycin D production from 240.7 +/- 18.9 to 360.8 +/-
      30.7 mg/L, attributed to the increased the expression of bacillomycin D synthesis
      related genes through enhancing the transcriptional level of comA, comP, and
      phrC. These results showed that the production of bacillomycin D in B.
      amyloliquefaciens fmbJ might be regulated by the RapC-PhrC system. The findings
      are expected to advance further agricultural application of Bacillus spp. as a
      promising source of natural bioactive compounds.

PMID- 29648450
TI  - Neuronal Synapses: Microscale Signal Processing Machineries Formed by Phase
      Separation?
AB  - The organization principles underlying non-membrane-bound organelles have started
      to unravel in the past 10 years. A new biophysical model known as biomolecular
      condensates has been proposed to explain many aspects of membraneless organelle
      assembly and regulation. Neurons are extremely complex, and each neuron can
      contain tens of thousands of synapses, building an extensive neuronal circuit.
      Intriguingly, neuronal synapses are characterized by specialized
      compartmentalization, where highly enriched supramolecular complexes are semi
      membrane-enclosed into submicrometer-sized signal processing compartments. Recent
      findings have demonstrated that this postsynaptic density may be driven by phase
      separation, and an increasing number of studies of membraneless compartments have
      shed light on the important molecular features shared by these organelles. Here,
      we discuss the unique morphology and composition of synapses and consider how
      synaptic assembly might be driven by phase separation. Understanding the
      molecular behavior of this semi-membrane-bound compartment could ultimately help
      to explain the mechanistic details underlying synaptic transmission and
      plasticity, as well as the numerous brain disorders caused by synaptic defects.

PMID- 29648453
TI  - Liquid Crystal Monomers (LCMs): A New Generation of Persistent Bioaccumulative
      and Toxic (PBT) Compounds?

PMID- 29648454
TI  - Effect of N-Linked Glycosylation of Recombinant Windmill Palm Tree Peroxidase on
      Its Activity and Stability.
AB  - Plant secretory peroxidases are valuable commercial enzymes. The windmill palm
      tree Trachycarpus fortunei produces one of the most stable and fastest
      peroxidases (WPTP) characterized to date; however, an economical source is
      needed. Pichia pastoris has been used as an expression system for WPTP and other
      peroxidases. However, yeast and plants synthesize different types of N-linked
      glycan structures and may differ the level of glycosylation at each site. Such
      non-native glycosylation can have unwanted consequences. Glycosylation site N256
      was under-glycosylated in the wild-type (1.5%) compared to the native enzyme
      (55%); therefore, we mutated WPTP to promote glycosylation at this site (WPTP
      E254G). Glycosylation increased four-fold, as measured by liquid chromatography
      tandem mass spectrometry. The mutation did not change the substrate specificity
      and optimal pH- and thermo-stability ranges, but it increased the catalytic
      activity 2-3-fold. In comparison with wild-type WPTP, WPTP E254G showed a shift
      of the most stable pH from 7 to 9, making it suitable for applications under
      alkaline conditions.

PMID- 29648455
TI  - Evaluating Iodine Uptake in a Crystalline Sponge Using Dynamic X-ray
      Crystallography.
AB  - The uptake of gaseous iodine into the crystalline sponge material
      [(ZnI2)3(tpt)2].0.7triphenylene.0.3PhNO2.0.7C6H12 1 (tpt = 2,4,6-tris(4-pyridyl)
      1,3,5-triazine) has been monitored by dynamic X-ray diffraction and
      thermogravimetric analysis. The X-ray analyses have enabled the location,
      quantity, uptake rate, and subsequent chemistry of the iodine upon inclusion into
      the pores to be determined. An uptake of 6.0 wt % (0.43 I2 per formula unit) was
      observed crystallographically over a period of 90 min before crystal degradation
      occurred. The included iodine molecules interact with the iodine atoms of the
      ZnI2 nodes at three different sites, forming coordinated I3- ions. The results
      contrast to recent observations on [(ZnI2)3(tpt)2] without the triphenylene
      guests which show the presence of I42- ions with low quantities of absorbed
      iodine.

PMID- 29648456
TI  - Multifunctional Vesicles from a Self-assembled Cluster-Containing Diblock
      Copolymer.
AB  - We describe a new diblock copolymer composed of two segments with complementary
      functionalities. One block contains pendent photo-cross-linkable cinnamoyl
      groups, and the other contains molecular clusters, Co6Se8, capable of
      multielectron redox processes. This multifunctional macromolecule is synthesized
      by sequential ring-opening metathesis polymerization of monomers constructed
      using norbornene moieties. Remarkably, the tethered molecular cluster gives
      access to three different charge states in N, N-dimethylformamide: neutral, +1,
      and +2. In tetrahydrofuran, by contrast, the charged copolymer self-assembles
      into vesicles that inhibit the redox reactions. The wall of these vesicles can be
      cross-linked by exploiting the photoinduced 2 + 2 cycloaddition of the cinnamoyls
      to form cyclobutane dimers. Moreover, these vesicles can be loaded with molecular
      cargo and used as cross-linkable containers; we demonstrate this feature by
      encapsulating the molecular dye methylene blue into the capsules. Our work is the
      first report of a well-defined block copolymer containing a metal chalcogenide
      molecular cluster; more generally, it opens the door to new applications of metal
      containing polymers.

PMID- 29648457
TI  - Critical Pedagogy and APA: A Resonant (and Timely) Interdisciplinary Blend.
AB  - Critical pedagogy owes much of its emergence, development, and ongoing relevance
      to the work of Paulo Freire whose legacy remains relevant for a next generation
      of scholars who seek to explore issues of inclusion, oppression, social justice,
      and authentic expression. An interdisciplinary dialogue between critical pedagogy
      and adapted physical activity is timely, appropriate, and should focus on complex
      profiles of neurodiversity, mental illness, and mental health, with emphasis on
      pedagogic practices of practitioners in service delivery and teacher educators
      who prepare them for professional practice. A case-based scenario approach is
      used to present practitioner and teacher educator practices. Concrete examples
      are provided for analyzing and understanding deeper issues and challenges related
      to neurodiversity in a variety of embodied dimensions in educational and activity
      contexts. We work with Szostak's approach to interdisciplinary research and model
      an analysis strategy that integrates and applies the methodological features of
      interdisciplinarity, adapted physical activity, and critical pedagogy.

PMID- 29648458
TI  - Human individual radiation sensitivity and prospects for prediction.
AB  - In the past few decades, it has become increasingly evident that sensitivity to
      ionising radiation is variable. This is true for tissue reactions (deterministic
      effects) after high doses of radiation, for stochastic effects following moderate
      and possibly low doses, and conceivably also for non-cancer effects such as
      cardiovascular disease, the causal pathway(s) of which are not yet fully
      understood. A high sensitivity to deterministic effects is not necessarily
      correlated with a high sensitivity to stochastic effects. The concept of
      individual sensitivity to high and low doses of radiation has long been supported
      by data from patients with certain rare hereditary conditions. However, these
      syndromes only affect a small proportion of the general population. More relevant
      to the majority of the population is the notion that some part of the genetic
      contribution defining radiation sensitivity may follow a polygenic model, which
      predicts elevated risk resulting from the inheritance of many low-penetrance risk
      modulating alleles. Can the different forms of individual radiation sensitivities
      be inferred from the reaction of cells exposed ex vivo to ionising radiation? Can
      they be inferred from analyses of individual genotypes? This paper reviews
      current evidence from studies of late adverse tissue reactions after radiotherapy
      in potentially sensitive groups, including data from functional assays, candidate
      gene approaches, and genome-wide association studies. It focuses on studies
      published in 2013 or later because a comprehensive review of earlier studies was
      published previously in a report by the UK Advisory Group on Ionising Radiation.

PMID- 29648459
TI  - Implementation of the integrated approach in different types of exposure
      scenarios.
AB  - The International Commission on Radiological Protection (ICRP) recognises three
      types of exposure situations: planned, existing, and emergency. In all three
      situations, the release of radionuclides into the natural environment leads to
      exposures of non-human biota, as well as the potential for exposures of the
      public. This paper describes how the key principles of the ICRP system of
      radiological protection apply to non-human biota and members of the public in
      each of these exposure situations. Current work in this area within ICRP Task
      Group 105 is highlighted. For example, how simplified numeric criteria may be
      used in planned exposure situations that are protective of both the public and
      non-human biota. In emergency exposure situations, the initial response will
      always be focused on human protection; however, understanding the potential
      impacts of radionuclide releases on non-human biota will likely become important
      in terms of communication as governments and the public seek to understand the
      exposures that are occurring. For existing exposure situations, there is a need
      to better understand the potential impacts of radionuclides on animals and
      plants, especially when deciding on protective actions. Understanding the
      comparative impacts from radiological, non-radiological, and physical aspects is
      often important in managing the remediation of legacy sites. Task Group 105 is
      making use of case studies of how exposure situations have been managed in the
      past to provide additional guidance and advice for the protection of non-human
      biota.

PMID- 29648460
TI  - The role of experts in postaccident recovery: lessons learnt from Chernobyl and
      Fukushima.
AB  - Following a nuclear accident, a major dilemma for affected people is whether to
      stay or leave the affected area, or, for those who have been evacuated, whether
      or not to return to the decontaminated zones. Populations who have to make such
      decisions have to consider many parameters, one of which is the radiological
      situation. Feedback from Chernobyl and Fukushima has demonstrated that
      involvement and empowerment of the affected population is a way to provide them
      with the necessary elements to make informed decisions and, if they decide to
      return to decontaminated areas, to minimise exposure by contributing to the
      development of a prudent attitude and vigilance towards exposure. However,
      involving stakeholders in postaccident management raises the question of the role
      of experts and public authorities in supporting the inhabitants who have to make
      decisions about their future. Based on experiences in Chernobyl and Fukushima,
      this paper will discuss various principles that have to be taken into account by
      experts and public authorities about their role and position when dealing with
      stakeholders in a postaccident recovery process.

PMID- 29648461
TI  - Using Two-Eyed Seeing to Explore Interagency Collaboration.
AB  - Background Health-care environments influence service delivery; approaches need
      to be more wholistic and culturally competent requiring effective interagency
      collaboration to bridge traditional Indigenous and mainstream health services.
      Despite considerable research on collaboration, the concept remains
      misunderstood, at worst, and formative, at best. Within the nexus of these two
      diverse health services, there is limited information on how collaborations could
      be created and sustained effectively. Purpose To explore the
      perspectives/experiences of collaboration of select Saskatchewan health
      professionals practicing across these diverse services to understand the concept
      from their perspectives. Methods This qualitative study explored collaboration
      through observation and interviews to elicit perspectives (two-eyed seeing) of
      health professionals working within the context of a traditional-mainstream
      health services partnership. Results Individual- and system-level factors and
      accountabilities are needed for successful cross-cultural collaboration and can
      be enabled by embedding the virtues of Indigenous and values of mainstream health
      services along with building and maintaining relationships, valuing difference,
      creating supportive environments and wholistic approaches, having the right
      people at the table, and making a change for impactful outcomes. Conclusion
      Findings support the need for implementing contextually relevant collaborative
      practice models for productive, wholistic health services. Two-eyed seeing
      provides the ability to capture and catalyze the tremendous value and strengths
      of both worlds, potentiating complementary aspects to meet the needs of clients
      and communities.

PMID- 29648462
TI  - A systematic review of neuroimaging findings in children and adolescents with
      sports-related concussion.
AB  - BACKGROUND: Sport-related concussion (SRC) generally does not result in
      structural anomalies revealed through clinical imaging techniques such as MRI and
      CT. While advanced neuroimaging techniques offer another avenue to investigate
      the subtle alterations following SRC, the current pediatric literature in this
      area has yet to be reviewed. The aim of this review is to systematically explore
      the literature on magnetic resonance spectroscopy (MRS), diffusion tensor imaging
      (DTI), functional magnetic resonance imaging (fMRI), and cortical thickness
      following SRC in children and adolescents. METHODS: A systematic Pubmed search
      using the preferred reporting items for systematic reviews and meta-analysis
      guidelines was conducted independently for each neuroimaging method. Studies were
      screened for inclusion based on pre-determined criteria. RESULTS: A total of 26
      studies were included (MRS = 4, DTI = 10, fMRI = 11, cortical thickness = 1). A
      total of 16 studies were conducted solely with male athletes, while 10 studies
      recruited an unequal number of male and female athletes. CONCLUSIONS: While MRI
      and CT are generally unrevealing, advanced neuroimaging techniques demonstrated
      neurometabolic, microstructural, and functional alterations following SRC in
      athletes younger than 19 years of age in the acute, subacute, and chronic phases
      of recovery. However, more studies are needed to fully understand the impact of
      SRC on the developing brain in children and adolescents.

PMID- 29648463
TI  - Protective effect of thymoquinone, the main component of Nigella Sativa, against
      diazinon cardio-toxicity in rats.
AB  - Several studies have shown that oxidative stress and cell damage can occur at
      very early stages of diazinon (DZN) exposure. The present study was designed to
      determine the beneficial effect of thymoquinone (Thy), the main component of
      Nigella sativa (black seed or black cumin), against DZN cardio-toxicity in rats.
      In the present experimental study, 48 male Wistar rats were randomly divided into
      six groups: control (corn oil gavages), DZN gavages (20 mg/kg/day), Thy gavages
      (10 mg/kg/day) and Thy + DVN gavages (2.5, 5 and 10 mg/kg/day). Treatments were
      continued for 28 days, then the animals were anesthetized by ether and superoxide
      dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), lactate
      dehydrogenize (LDH) and glutathione peroxide (GPX) activity was evaluated. In
      addition, glutathione (GSH) and malondialdehyde (MDA) the heart tissue and
      creatinephosphokinase-MB (CPK-MB) and troponin (TPI) levels and cholinesterase
      activity in the blood were evaluated. DZN-induced oxidative damage and elevated
      the levels of the cardiac markers CK-MB, TPI, MDA and LDH and decreased SOD, CAT
      and cholinesterase activity and GSH level compared with the control group.
      Treatment with Thy reduced DZN cardio-toxicity and cholinesterase activity. The
      success of Thy supplementation against DZN toxicity can be attributed to the
      antioxidant effects of its constituents. Administration of Thy as a natural
      antioxidant decreased DZN cardio-toxicity and improved cholinesterase activity in
      rats through the mechanism of free radical scavenging.

PMID- 29648465
TI  - Continuous Glucose Monitoring (CGM) or Blood Glucose Monitoring (BGM):
      Interactions and Implications.
AB  - At the 2017 10th annual International Conference on Advanced Technologies and
      Treatments for Diabetes (ATTD) in Paris, France, four speakers presented their
      perspectives on the roles of continuous glucose monitoring (CGM) and of blood
      glucose monitoring (BGM) in patient management within one symposium. These
      presentations included discussions of the differences in the accuracy of CGM and
      BGM, a clinical perspective on the physiological reasons behind differences in
      CGM and BGM values, and an overview of the impact of variations in device
      accuracy on patients with diabetes. Subsequently a short summary of these
      presentations is given, highlighting the value of good accuracy of BGM or CGM
      systems and the ongoing need for standardization. The important role of both BGM
      and CGM in patient management was a theme across all presentations.

PMID- 29648464
TI  - Home blood pressure and cardiovascular outcomes in very elderly patients
      receiving antihypertensive drug therapy: a subgroup analysis of Home blood
      pressure measurement with Olmesartan Naive patients to Establish Standard Target
      blood pressure (HONEST) study.
AB  - The appropriate target blood pressure (BP) in elderly patients with hypertension
      remains uncertain. We investigated the relationship between morning home systolic
      blood pressure (MHSBP) during follow-up and cardiovascular (CV) risk in
      outpatients receiving olmesartan-based treatment aged <75 years (n = 16799) and
      >=75 years (n = 4792) in the HONEST study. In the follow-up period (mean 2.02
      years), the risk for major CV events was significantly higher in patients with
      MHSBP >=155 mmHg compared with <125 mmHg in both age groups in Cox proportional
      hazards model adjusted for other risk factors and there was no significant
      difference in trend between the two groups (interaction P = 0.9917 for MHSBP).
      Hazard ratios for CV events for 1-mmHg increase in MHSBP were similar in patients
      aged <75 years and in patients aged >=75 years. The incidence of adverse drug
      reactions related to excessive BP lowering was lower in patients <75 years than
      in patients >=75 years (0.73 vs 1.02%, P = 0.0461). In conclusion, the study
      suggests even in patients >=75 years antihypertensive treatment targeting the
      same MHSBP levels in patients <75 years may be beneficial in reducing CV risk
      when treatment is tolerated.

PMID- 29648466
TI  - The mandate and work of ICRP Committee 1 on radiation effects.
AB  - The aim of the International Commission on Radiological Protection (ICRP) is to
      protect humans against cancer and other diseases and effects associated with
      exposure to ionising radiation, and also to protect the environment, without
      unduly limiting the beneficial use of ionising radiation. As of the second half
      of 2017, four committees are contributing to the overall mission of ICRP,
      including Committee 1 (Radiation Effects). The role of Committee 1 includes
      consideration of the risks and mechanisms of induction of cancer and heritable
      disease; discussion of the risks, severity, and mechanisms of induction of
      tissue/organ damage and developmental defects; and review of the effects of
      ionising radiation on non-human biota at population level. This paper gives an
      overview of the recent activities of Committee 1, and discusses the focus of its
      active task groups.

PMID- 29648467
TI  - The relationship between gestational diabetes mellitus and selenoprotein-P plasma
      1 (SEPP1) gene polymorphisms.
AB  - Our aim is to demonstrate any correlation between gestational diabetes mellitus
      (GDM) and polymorphism of the selenoprotein P (SEPP1) gene encoding the SEPP1
      protein, having a role in the insulin resistance in GDM. Forty pregnant women
      with GDM and 40 healthy pregnant women were included in the study. In both
      groups, single nucleotide polymorphisms (SNPs), specifically, rs4987017,
      rs13154178, rs146125471, rs28919926, and rs16872762 were studied. There was no
      difference between the groups in terms of polymorphism rs146125471, rs28919926,
      or rs16872762 (p > .05). There was a significant difference in SNP rs13154178
      polymorphism between the two groups (p < .01). When rs13154178 gene polymorphism
      was compared with AA homozygous individuals, fasting blood glucose levels were
      significantly higher in carriers of either polymorphism than in those with no
      polymorphism (p < .001). We suggest rs13154178 gene polymorphism may lead to GDM
      in the Turkish society.

PMID- 29648468
TI  - In healthy normotensive subjects age and blood pressure better predict
      subclinical vascular and cardiac organ damage than atherosclerosis biomarkers.
AB  - PURPOSE: Only few studies evaluated biomarkers useful for defining the
      cardiovascular risk of a subject in a pre-clinical condition (i.e. healthy
      subjects). In this context we sought to determine the relationships of
      Plasminogen activator inhibitor type 1 (PAI-1), P-Selectin, Tissue Inhibitors
      Metalloproteinases type 1 (TIMP-1) and Cystatin-C with subclinical Target Organ
      Damage (TOD) in normotensive and normoglycemic subjects without known
      cardiovascular and kidney diseases. MATERIALS AND METHODS: 480 blood donors
      participated at the present analysis. TOD was evaluated as Pulse Wave Velocity
      (PWV), Left Ventricular Hypertrophy (LVH) and Intima Media Thickness (IMT) and
      carotid plaque presence) grouped together under carotid TOD. RESULTS: 3.1% of the
      subjects showed a PWV higher than 10 m/sec with those subjects exerting
      significantly lower values of P-Selectine (0.068 +/- 0.015 vs 0.08 +/- 0.036
      mg/L, p = .014). 8.8% of the subjects showed carotid TOD that was associated with
      higher Cystatin-C values (0.67 +/- 0.17 vs 0.63 +/- 0.14 mg/L, p = .045). Finally
      23.8% of the subjects showed LVH with no significant differences regarding
      biomarkers. Despite some significant correlations between biomarkers and TOD, at
      the multivariate analysis none came out to be as significant predictor of the
      assessed TOD. CONCLUSIONS: in normotensive and normoglycemic healthy subjects,
      the evaluated biomarkers of atherosclerotic process didn't show any significant
      association with cardiac, carotid and vascular TOD while age and BP are its
      principal predictors.

PMID- 29648469
TI  - The stimulation of the vaginal immune system with short-term administration of a
      vaginal gel containing fraction of Propionibacterium acnes, hyaluronic acid and
      polycarbophil is efficacious in vaginal infections dependent on disorders in the
      vaginal ecosystem.
AB  - The vaginal immune system (VIS) is the first defense against antigens recognized
      as foreign. Substances capable of locally activating the VIS could be a valid
      strategy to treat vulvo-vaginal infections (VVI), caused by changes in the
      vaginal ecosystem, such as bacterial vaginosis (BV), vulvo-vaginal candidiasis
      (CA), and mixed vaginitis (MV). Bacterial lysates, obtained by crushing bacterial
      cultures, exert immuno-modulatory activities. The parietal fraction from
      Propionibacterium acnes is a patent of Depofarma (MoglianoVeneto, Italy). The
      preparation that associates such fraction to hyaluronic acid and polycarbophil is
      a registered trademark, commercially available in Italy as vaginal gel,
      Immunovag(r). The study aimed to evaluate whether a 5-day-treatment with
      Immunovag(r) improves the symptoms and signs of VVI, in 60 women with Gardnerella
      vaginalis (GV), 154 with CA, 95 with MV, diagnosed with vulvar vaginal swab
      (VVS), and in 283 with BV, diagnosed with the Amsel criteria. At the end of the
      treatment (visit 2), the symptoms and signs of VVI disappeared in a significant
      number of subjects (chi2p < .02 vs pre-treatment) in all VVI groups, and their
      intensity was significantly (p < .0002) reduced in the subjects in which they
      were still present. Immunovag(r) represents a valid treatment of VVI induced by
      changes in the vaginal ecosystem.

PMID- 29648471
TI  - Heritability of Geographic Range Sizes Revisited: A Reply to Hunt et al.

PMID- 29648470
TI  - Inhibitory effect of chlormethiazole on the toxicokinetics of diethylnitrosamine
      in normal and hepatofibrotic rats.
AB  - The effect of chlormethiazole (CMZ) at single and multiple doses on the
      toxicokinetics of diethylnitrosamine (DEN) was investigated in normal rats and
      those with DEN-induced liver fibrosis. Twelve rats were treated with DEN (50
      mg/kg) alone and in combination with a single dose of CMZ (10, 50, or 100 mg/kg)
      by intraperitoneal (i.p.) injection. In a multiple dose test, six rats were
      treated with CMZ (50 mg/kg) for 7 d with addition of DEN (50 mg/kg) on days 1 and
      7. Lastly, 12 rats were treated with DEN (50 mg/kg) by i.p. injection twice a
      week for 4 consecutive weeks, followed by weekly injections for another 8 weeks
      to build the model of liver fibrosis. Following this induction, the 12 rats were
      given CMZ (50 mg/kg) combined with DEN (50 mg/kg) to study the inhibitory effect
      of CMZ on DEN metabolism in hepatofibrotic rats. Serial blood samples were also
      collected and analyzed by a validated high-performance liquid chromatography
      (HPLC) method. A single-dose CMZ treatment decreased DEN clearance (CL),
      prolonged the t1/2, and increased the 'area under the curve' (AUC) for DEN in
      normal and hepatofibrotic rats relative to rats that did not receive CMZ.
      Treatment with CMZ for 7 d further prolonged the t1/2 for DEN but did not alter
      the CL and AUC relative to a single CMZ treatment. These results suggest that CMZ
      significantly inhibits the metabolism of DEN in normal and hepatofibrotic rats.

PMID- 29648473
TI  - The Fourth International Symposium on the System of Radiological Protection.

PMID- 29648472
TI  - Downregulation of serum long noncoding RNA GAS5 may contribute to insulin
      resistance in PCOS patients.
AB  - Polycystic ovary syndrome (PCOS) is a common endocrine disease that affects
      reproductive-aged women and mostly characterized by insulin resistance (IR). The
      underlying mechanism remains unknown. Long noncoding RNAs (lncRNAs) have been
      demonstrated to be involved in various levels of biological regulation process of
      cell development, metabolism, and differentiation. This study aims to investigate
      the relationship between IR and differential expression of lncRNA Growth-arrest
      specific transcript 5 (GAS5) in patients' serum with and without PCOS. A total of
      76 cases of serum was collected from non-PCOS and PCOS patients with and without
      IR to measure interleukin-18 (IL-18) and GAS5 expression, which were correlated
      with IR status. The IL-18 concentration in serums was significantly increased in
      PCOS patients with IR. GAS5 expression was decreased in serums in PCOS patients
      with IR. Result of correlation analysis shows that there is a negative
      association between GAS5 expression and homeostasis model of assessment for
      insulin resistance (HOMA-IR). GAS5 was yielded the ROC curve (AUC). Our study
      implied that elevated IL-18 expression and downregulation of GAS5 in serums might
      contribute to IR in PCOS patients.

PMID- 29648474
TI  - Postoperative New-Onset Pseudoparalysis: A Retrospective Analysis of 430
      Consecutive Arthroscopic Repairs for Large to Massive Rotator Cuff Tears.
AB  - BACKGROUND: The authors have sometimes encountered postoperative new-onset
      pseudoparalysis (PONP) after arthroscopic repair for large to massive rotator
      cuff tear (ARCR). As there are insufficient data regarding PONP, the authors
      aimed to determine whether such a condition is characterized by obvious risk
      factors, as well as to assess the conditions under which it can be reversed.
      PURPOSE: To evaluate the predictors of PONP development after ARCR and its
      reversal and to integrate these predictors into a scoring system that can be
      applied in clinical practice. STUDY DESIGN: Case-control study; Level of
      evidence, 3. METHODS: The authors retrospectively analyzed 430 consecutive ARCRs
      performed between March 2010 and May 2016. Patients were stratified according to
      the occurrence of PONP. To determine the risk factors of PONP, the authors
      compared the PONP and control groups (patients who did not experience PONP) in
      terms of demographic, clinical, and operative characteristics. Results were
      expressed in terms of odds ratios (ORs). RESULTS: The incidence of PONP was 6.0%
      (26 of 430). Predictors of PONP included torn subscapularis (OR, 7.875; 95% CI,
      1.780-34.956; P = .007), >=30-mm retraction of the torn supraspinatus (OR, 4.657;
      95% CI, 1.537-14.203; P = .007), age >=65 years (OR, 3.865; 95% CI, 1.465-10.040;
      P = .006), and preoperative stiffness (OR, 2.954; 95% CI, 1.212-7.159; P = .017).
      The reversal rate of PONP was 65.4% (17 of 26), and the mean time to PONP
      reversal was 10 months. The occurrence and reversal of PONP were not related to
      retear. Fatty infiltration of the supraspinatus lower than Goutallier grade 3 was
      the sole predictor of reversal (OR, 22.000; 95% CI, 1.857-260.648; P = .014).
      CONCLUSION: Although the incidence of PONP after ARCR was low (6.0%), the risk of
      PONP was higher in patients with a torn subscapularis, larger supraspinatus tear
      size, older age, and preoperative stiffness. The mean time from PONP onset to
      reversal was 10 months, and PONP reversal was affected solely by fatty
      infiltration of the supraspinatus. Therefore, surgeons should consider the risk
      for PONP and attempt to identify high-risk patients before rotator cuff repair.

PMID- 29648475
TI  - Alterations in plasma L-arginine and methylarginines in heart failure and after
      heart transplantation.
AB  - OBJECTIVE: Endothelial function, including the nitric oxide (NO)-pathway, has
      previously been extensively investigated in heart failure (HF). In contrast,
      studies are lacking on the NO pathway after heart transplantation (HT). We
      therefore investigated substances in the NO pathway prior to and after HT in
      relation to hemodynamic parameters. DESIGN: 12 patients (median age 50.0 yrs, 2
      females), heart transplanted between June 2012 and February 2014, evaluated at
      our hemodynamic lab, at rest, prior to HT, as well as four weeks and six months
      after HT were included. All patients had normal left ventricular function post
      operatively and none had post-operative pulmonary hypertension or acute cellular
      rejection requiring therapy at the evaluations. Plasma concentrations of ADMA,
      SDMA, L-Arginine, L-Ornithine and L-Citrulline were analyzed at each evaluation.
      RESULTS: In comparison to controls, the plasma L-Arginine concentration was low
      and ADMA high in HF patients, resulting in low L-Arginine/ADMA-ratio pre-HT.
      Already four weeks after HT L-Arginine was normalized whereas ADMA remained high.
      Consequently the L-Arginine/ADMA-ratio improved, but did not normalize. The
      biomarkers remained unchanged at the six-month evaluation and the L-Arginine/ADMA
      ratio correlated inversely to pulmonary vascular resistance (PVR) six months post
      HT. CONCLUSIONS: Plasma L-Arginine concentrations normalize after HT. However, as
      ADMA is unchanged, the L-Arginine/ADMA-ratio remained low and correlated
      inversely to PVR. Together these findings suggest that (i) the L-Arginine/ADMA
      ratio may be an indicator of pulmonary vascular tone after HT, and that (ii) NO
      dependent endothelial function is partly restored after HT. Considering the good
      postoperative outcome, the biomarker levels may be considered "normal" after HT.

PMID- 29648476
TI  - Does the type of GnRH analogue used, affect live birth rates in women with
      endometriosis undergoing IVF/ICSI treatment, according to the rAFS stage?
AB  - Since the introduction of gonadotropin-releasing hormone (GnRH) antagonists, an
      extensive amount of literature investigating the role of the downregulation
      protocols on pregnancy outcomes has been published. However, these studies were
      mainly performed in the general infertile population where patients with
      endometriosis were often excluded or underrepresented. This study is a large
      retrospective cohort study including 386 endometriosis patients undergoing
      IVF/ICSI, who had been previously classified according to the rAFS system.
      Patients were stimulated either a long GnRH agonist or GnRH antagonist protocol.
      Depending on endometriosis stage, patients were divided into two groups:
      endometriosis stage I-II and endometriosis stage III-IV. Each group was
      subdivided, based on the type GnRH analog used. When comparing the GnRH agonist
      and antagonist groups, patients with endometriosis stage I-II, had a tendency
      toward higher beta-hCG positive, clinical pregnancy, and live birth rates (42.8%
      vs. 26.7%; p = .07) in favor of GnRH agonist use. In endometriosis stage III-IV,
      no differences were observed between agonist and antagonist cycle in any of the
      pregnancy outcomes. Multivariate regression analysis did not reveal any
      significant predictor of live birth after adjusting for relevant confounders.
      Based on our findings, the chance to have a liveborn in endometriosis population
      seems not to be affected by the type of GnRH analog used, at least in advanced
      stages. Findings from stage I-II endometriosis cases merit consideration and
      further evaluation in a larger sample size is warranted.

PMID- 29648477
TI  - Acute intensive care unit management of mustard gas victims: the Turkish
      experience.
AB  - PURPOSE: Sulphur mustard (SM) is an highly toxic and vesicant chemical weapon
      that was used in various military conflicts several times in the history. The
      severity of ocular, dermal, and pulmonary symptoms that may appear following a
      characteristic asymptomatic period are depending on the SM concentration and
      exposure duration. The aim of this study is to present the clinical features and
      share the intensive care unit (ICU) experiences for the medical management of
      mustard gas victims. MATERIALS AND METHODS: Thirteen Free Syrian Army soldiers
      near Al-Bab region of North Syria were reportedly exposed to oily blackish smoke
      with garlic smell due to the explosion of a trapped bomb without causing any
      blast or thermal effect on 26th November 2016. None of them wore any chemical
      protective suits or gas masks during explosion. Since they observed skin lesions
      including bullous formation next day, they were admitted to the Turkish Field
      Hospital at the Turkish - Syrian border and then evacuated to the State Hospital
      of Gaziantep Province, Turkey for further management. Eight victims who were very
      close to point of explosion suffered burning eyes, sore throat, dry cough and
      dyspnoea after the chemical attack. RESULTS: On admission to hospital, all cases
      had conjunctivitis, hoarseness and bullae on various body areas. Blepharospasm
      and opacity were found in 8 patients and 5 of them had corneal erosions and
      periorbital oedema. Temporary loss of vision in 4 cases lasted for 24 h. Multiple
      fluid-filled blisters were observed especially on the scalp, neck, arms and
      hands, where direct skin exposure to the agent occurred. A definitive clinical
      care and infection prophylaxis measures along with the burn treatment and
      bronchodilators for respiratory effects were applied in ICU. Two patients
      received granulocyte-colony-stimulating factor due to the SM-mediated bone marrow
      suppression on the 16th day of exposure and one of them died because of necrotic
      bronchial pseudomembrane obstruction resulting in cardiopulmonary arrest.
      CONCLUSIONS: SM was first used during the First World War and it is still
      considered one of the major chemical weapons recently used by non-state actors in
      Syria and Iraq. In case of SM exposure, medical treatment of SM-induced lesions
      is symptomatic because no antidote or causal therapy does exist even though SM is
      very well known for over 100 years. However, clinical management in intensive
      care medicine of SM victims have improved since the 1980s, this study which is
      one of the largest recent SM-exposed case series since that time is important for
      the contribution to the clinical experience.

PMID- 29648478
TI  - Role of individual dosimetry for affected residents in postaccident recovery: the
      Fukushima experience.
AB  - The accident at Fukushima Daiichi nuclear power plant on 11 March 2011 released
      radioactive material into the atmosphere, and contaminated land in Fukushima and
      several neighbouring prefectures. During rehabilitation, it is important to
      accurately understand and determine individual external doses to allow
      individuals to make informed decisions about whether or not to return to the
      affected areas. Personal dosimeters (D-Shuttle), used together with a global
      positioning system and geographic information system device, can provide
      realistic individual external doses and associated individual external doses,
      ambient doses, and activity patterns of individuals in the affected areas of
      Fukushima. This study involved more than 250 affected residents. The results help
      to determine realistic individual external doses, and corresponding time-activity
      patterns and airborne monitoring ambient dose rates, which can be used to predict
      future cumulative external doses after residents return to their homes in
      evacuation areas. In addition, insights gained by the study can help to explain
      the role of individual external dose measurements for affected residents in
      postaccident recovery, based mainly upon the experience gained in measuring,
      assessing, and communicating individual external doses.

PMID- 29648479
TI  - Dietary intervention and health in patients with systemic lupus erythematosus: A
      systematic review of the evidence.
AB  - OBJECTIVE: The aim of this study was to evaluate the scientific evidence of
      dietary intervention, either through diet or supplementation, and its effects on
      the health of patients with systemic lupus erythematosus. METHODS: Literature
      searches were conducted using Scopus, PubMed, BioMed Central and Science Direct
      databases. The terms used for the search were diet, nutritional support,
      nutrition therapy and systemic lupus erythematosus. RESULTS: Eleven studies with
      interventions related to supplementation of omega-3 fatty acids, vitamin D and
      turmeric, as well as changes in diet composition, such as low glycaemic index
      diet were identified. CONCLUSIONS: The studies evidenced that omega-3
      supplementation reduced inflammation, disease activity, endothelial dysfunction
      and oxidative stress; vitamin D supplementation increased serum levels, reduced
      inflammatory and hemostatic markers; turmeric supplementation reduced
      proteinuria, hematuria and systolic blood pressure; and low glycaemic index diet
      caused weight loss and reduced fatigue.

PMID- 29648481
TI  - Induction of chromosomal aberrations and micronuclei by 2-hydroxy-4
      methoxybenzophenone (oxybenzone) in human lymphocytes.
AB  - Oxybenzone or benzophenone-3 (2-hydroxy-4-methoxybenzophenone; BP-3) is a filter
      used in a variety of personal care products for protection of human skin and hair
      from damage by ultraviolet radiation. BP-3 is suspected to exhibit endocrine
      disruptive properties. Indeed, it was found to be able to interact with the
      endocrine system causing alteration of its homeostasis, with consequent adverse
      health effects. Moreover, it is ubiquitously present in the environment, mostly
      in aquatic ecosystems, with consequent risks to the health of aquatic organisms
      and humans. In the present study, we analyzed the cytogenetic effects of BP-3 on
      human lymphocytes using in vitro chromosomal aberrations and micronuclei assays.
      Blood samples were obtained from five healthy Italian subjects. Lymphocyte
      cultures were exposed to five concentrations of BP-3 (0.20, 0.10, 0.05, 0.025,
      and 0.0125 MUg/mL) for 24 and 48 h (for chromosomal aberrations and micronuclei
      tests, respectively). The concentration of 0.10 ug/mL represents the
      acceptable/tolerable daily intake reference dose established by European Union,
      whereas 0.20, 0.05, 0.025, and 0.0125 ug/mL represent multiple and sub-multiple
      of this concentration value. Our results reported cytogenetic effects of BP-3 on
      cultured human lymphocytes in terms of increased micronuclei and chromosomal
      aberrations' frequencies at all tested concentrations, including concentrations
      lower than those established by European Union. Vice versa, after 48-h exposure,
      a significant reduction of the cytokinesis-block proliferation index value in
      cultures treated with BP-3 was not observed, indicating that BP-3 does not seem
      to produce effects on the proliferation/mitotic index when its concentration is
      equal to or less than 0.20 MUg/mL.

PMID- 29648480
TI  - Sex differences impact the lung-bone inflammatory response to repetitive inhalant
      lipopolysaccharide exposures in mice.
AB  - Skeletal health consequences associated with inflammatory diseases of the airways
      significantly contribute to morbidity. Sex differences have been described
      independently for lung and bone diseases. Repetitive inhalant exposure to
      lipopolysaccharide (LPS) induces bone loss and deterioration in male mice, but
      comparison effects in females are unknown. Using an intranasal inhalation
      exposure model, 8-week-old C57BL/6 male and female mice were treated daily with
      LPS (100 ng) or saline for 3 weeks. Bronchoalveolar lavage fluids, lung tissues,
      tibias, bone marrow cells, and blood were collected. LPS-induced airway
      neutrophil influx, interleukin (IL)-6 and neutrophil chemoattractant levels, and
      bronchiolar inflammation were exaggerated in male animals as compared to female
      mice. Trabecular bone micro-CT imaging and analysis of the proximal tibia were
      conducted. Inhalant LPS exposures lead to deterioration of bone quality only in
      male mice (not females) marked by decreased bone mineral density, bone
      volume/tissue volume ratio, trabecular thickness and number, and increased bone
      surface-to-bone volume ratio. Serum pentraxin-2 levels were modulated by sex
      differences and LPS exposure. In proof-of-concept studies, ovarectomized female
      mice demonstrated LPS-induced bone deterioration, and estradiol supplementation
      of ovarectomized female mice and control male mice protected against LPS-induced
      bone deterioration findings. Collectively, sex-specific differences exist in LPS
      induced airway inflammatory consequences with significant differences found in
      bone quantity and quality parameters. Male mice demonstrated susceptibility to
      bone loss and female animals were protected, which was modulated by estrogen.
      Therefore, sex differences influence the biologic response in the lung-bone
      inflammatory axis in response to inhalant LPS exposures.

PMID- 29648483
TI  - Zoledronic acid induces cytogenetic toxicity in male germline cells of Swiss
      albino mice.
AB  - This study mainly focuses on the cytogenetic toxicity induction by zoledronic
      acid (ZA), a nitrogen containing bisphosphonate (N-BPs) in the male germline
      cells of Swiss albino mice. A single intraperitoneal exposure with three
      different doses of ZA (2, 4, and 8 mg/kg body weight), toxicity was assessed by
      analyzing spermatogonial metaphase chromosome aberrations at 24 h, aberrant
      primary spermatocytes at week 4, and abnormal spermatozoa at week 8
      posttreatment. Cyclophosphamide (40 mg/kg) and 0.9% NaCl were used as positive
      and vehicle controls respectively in the study. The results showed that there was
      a significant induction in the number of chromosomal aberrations especially at
      two doses of ZA (4 and 8 mg/kg) after 24 h in the spermatogonial cells (p <
      0.001) compared to vehicle control. The transmission genetic damages were noticed
      as aberrant spermatocytes with atypical bivalents (X-Y/autosomal asynapsis) at 4
      mg/kg of ZA (p < 0.01) and at 8 mg/kg of ZA (p < 0.001) at week 4 posttreatment.
      A statistically significant higher number of abnormal spermatozoa (sperm) were
      also noticed at week 8 posttreatment of both at 4 and 8 mg/kg of ZA (p < 0.001).
      Hence, from these genotoxicity studies, it can be concluded that ZA is genotoxic
      in male germline cells and has the potential of transmitting the genotoxic
      effects from spermatogonial cells to sperm in male Swiss mice.

PMID- 29648482
TI  - Acute chest syndrome in sickle cell disease.
AB  - Acute chest syndrome (ACS) is a leading complication of sickle cell disease (SCD)
      with significant morbidity and mortality. ACS is the most common cause of death
      and the second most common cause of hospitalization in patients with SCD.
      Delineating the specific cause of ACS is often difficult, and multiple risk
      factors that precipitate ACS frequently coexist. The prominent risk factors
      include infection, hypoxia, bronchial hyperresponsiveness, the SCD genotype, and
      opioid use. The key to the successful treatment of ACS is early recognition and
      initiation of treatment without delay. The main goal is to prevent and treat
      acute respiratory failure and, thus, minimize irreversible lung damage. This
      review focuses on the risk factors, pathogenesis, clinical presentation, and
      management of ACS.

PMID- 29648484
TI  - Serum periostin levels serve as a biomarker for both eosinophilic airway
      inflammation and fixed airflow limitation in well-controlled asthmatics.
AB  - OBJECTIVE: Periostin, a matricellular protein, is produced from airway epithelial
      cells and lung fibroblasts by IL-13. It has been suggested that periostin is
      involved in allergic inflammation and fibrosis. However, the usefulness of serum
      periostin measurement in the assessment of airway inflammation and remodeling and
      management of asthmatic patients is still debated. We aimed to determine whether
      serum periostin levels reflect eosinophilic airway inflammation and airway
      remodeling in asthma. METHODS: We examined the relationship of serum periostin
      levels with clinical features, biomarkers for eosinophilic airway inflammation,
      fraction of exhaled nitric oxide (FeNO) levels and blood eosinophil counts, and
      pulmonary functions in 235 well-controlled asthmatic patients on inhaled
      corticosteroids (ICS) treatment. RESULTS: Serum periostin levels were positively
      correlated with blood eosinophil counts (%) and age (r = 0.36 and 0.23,
      respectively), and were negatively correlated with body weight and FEV1/FVC (%)
      (r = -0.24 and - 0.23, respectively) in well-controlled asthmatic patients on ICS
      treatment (daily dose of 453 ug equivalent to fluticasone propionate). Blood
      eosinophil counts and serum periostin levels were similarly associated with
      increased FeNO levels (>=40 ppb) in the asthmatics. Serum periostin levels were
      better associated with fixed airflow limitation (FEV1/FVC ratio <70%) than FeNO
      levels, blood eosinophil counts or total IgE levels in the asthmatics.
      Multivariate analysis showed that fixed airflow limitation was significantly
      associated with high serum periostin levels (>=97 ng/ml) (Odds ratio 3.2).
      CONCLUSIONS: Serum periostin levels serve as a biomarker for both eosinophilic
      airway inflammation and fixed airflow limitation in well-controlled asthmatics on
      ICS treatment.

PMID- 29648485
TI  - Biochemical, hematological, and hormonal profile of rats orally administered
      methanol stem bark extract of Napoleona vogelii Hook and Planch (Lecythidaceae).
AB  - Napoleona vogelii is used in traditional medicine for the management of stomach
      aches, ulcer, and cancers. This study was conducted to investigate the subchronic
      toxicological effect of methanol stem bark extract of N. vogelii on biochemical,
      hematological, and hormonal profile of male and female rats. Forty rats of both
      sexes were randomly divided into four groups of 10 rats each and were
      administered 100, 200, and 400 mg/kg of the extract p.o. for 90 d. Ten milliliter
      per kilogram of distilled water p.o. was administered to control rats. On
      hematological assessment, mean corpuscular hemoglobin concentration was
      significantly (p < 0.01) increased at 400 mg/kg compared to control. Biochemical
      assessment showed a significant increase (p < 0.05) in levels of alanine
      aminotransferase and aspartate aminotransferase at 200 and 400 mg/kg,
      respectively, compared to control. Hormonal assessment of male rats revealed a
      significantly (p < 0.0001) reduced level of testosterone at all treatment doses
      compared to control while estradiol was significantly (p < 0.05) reduced at 100
      mg/kg, but significantly (p < 0.0001) increased at 200 and 400 mg/kg respectively
      compared to control in female rats. Findings from this study demonstrate that N.
      vogelli is relatively safe on oral acute exposure but may possess the potential
      to cause hepatic dysfunction and infertility in male rats by perturbations of the
      hypothalamic-pituitary axis while conversely enhancing fertility in female rats
      on subchronic administration.

PMID- 29648486
TI  - Physicians' attitudes when faced with life-threatening events in children with
      severe neurological disabilities.
AB  - PURPOSE: Children with severe neurological disabilities are at an increased risk
      of acute, life-threatening events. We assessed physicians' attitudes when making
      decisions in these situations. METHODS: We surveyed physicians in pediatric
      intensive care, neurology, and rehabilitation units in Swiss hospitals. The
      questionnaire explored participants' attitudes toward life-threatening situations
      in two scenarios: a child with profound intellectual and multiple disabilities
      (PIMD) and an infant with spinal muscular atrophy (SMA) type I. RESULTS: The
      participation rate was 55% (52/95). There was a consensus favoring non-invasive
      ventilation and comfort care as well as avoiding tracheostomy and invasive
      ventilation. For the child with PIMD, 61% of participants opposed cardiopulmonary
      resuscitation (CPR), 51% for the child with SMA. Physicians with over 20 years of
      experience were significantly more opposed to providing CPR than less experienced
      colleagues. CONCLUSIONS: Physicians held different views, influenced by personal
      factors. This highlights the importance of standardizing multidisciplinary
      processes toward approaching these complex situations.

PMID- 29648487
TI  - BDNF expression increases without changes in play behavior following concussion
      in juvenile rats (Rattus Norvegicus).
AB  - PURPOSE: Young children have a high risk of concussion or mild traumatic brain
      injury (mTBI). Children often appear healthy soon after mTBI, but some have
      pervasive cognitive and/or motor impairments. Understanding underlying mechanisms
      recruited after concussion may help for return to play protocols and mitigating
      what might be lifelong impairments. METHODS: We investigated molecular and
      behavioral changes in a rat model of childhood concussion. Rats received an
      injury or sham procedure at an age approximately equivalent to the human period
      of early childhood. Social play was analyzed for behavioral differences. Tissue
      from the right motor cortex (impacted), left motor cortex, and medial prefrontal
      cortex were analyzed for brain derived neurotrophic factor (BDNF) protein.
      RESULTS: Play behavior was not significantly different between conditions. BDNF
      levels were much higher in both the right and left motor cortices of the mTBI
      group compared to medial prefrontal cortex, which is relatively remote from the
      impact site, within the mTBI group and all tissue collected from the sham group.
      CONCLUSIONS: There is ongoing plastic change at the cellular level in both the
      impacted area and the well-connected contralateral area after a concussion,
      suggesting compensatory mechanisms after injury are still at play.

PMID- 29648488
TI  - The long-term effects of conductive education courses in young children with
      cerebral palsy: a randomized controlled trial.
AB  - PURPOSE: To assess the additional long-term effects of multiple conductive
      education (CE) courses followed by conventional practice on functional skills and
      quality of life in children with cerebral palsy (CP) compared to a 4-month CE
      course delay including conventional practice. METHODS: Twenty-one children with
      CP, 3-6 years and varied functional levels, were randomized to 3-week CE
      course(s) followed by conventional practice or 4 months on a waiting list,
      including conventional practice and followed by CE-courses. Outcomes were
      measured 8 and 12 months after baseline. A web-based log collected data on
      conventional practice. RESULTS: We found no interaction between group assignment
      and time on functional skills and quality of life in children with CP at 8 and 12
      months. Two thirds of the children in both groups performed a large amount of
      conventional practice. CONCLUSIONS: No added long-term effects of CE courses were
      found. Larger controlled CE studies are needed.

PMID- 29648489
TI  - Marginal bone level in two Danish cross-sectional population samples in 1997-1998
      and 2007-2008.
AB  - OBJECTIVE: The aim of this study was to compare the marginal bone level of two
      randomly selected population samples from 1997/1998 and 2007/2008, with special
      emphasis on the role of smoking habits and gender. MATERIALS AND METHODS: Two
      cross-sectional randomly selected population samples [1997/1998 (N = 616) and
      2007/2008 (N = 396)] were analysed with respect to the marginal bone level. The
      marginal bone level was measured in full-mouth intraoral radiographs. Information
      on smoking was gathered using questionnaires. Multiple regression analysis was
      used in order to adjust for correlating factors (gender, age, smoking habits and
      number of teeth). RESULTS: After adjusting for confounding factors, the
      population sample from 2007/2008 had on average a slightly, but statistically
      significantly, more reduced average marginal bone level (0.15 mm) than the
      population sample from 1997/1998. Men had more reduced marginal bone level than
      women (0.12 mm). Smokers in both population samples had more reduced marginal
      bone level than non-smokers (0.39 mm and 0.12 mm for 1997/1998; 0.65 mm and 0.16
      mm for 2007/2008). CONCLUSIONS: In these populations, sampled 10 years apart, the
      2007/2008 population sample had a slightly more reduced marginal bone level than
      the 1997/1998 population sample. Men had more reduced marginal bone level than
      women, and smoking is considered a major risk factor for a reduced marginal bone
      level.

PMID- 29648491
TI  - Sublingual administration of 2-hydroxyethyl methacrylate enhances antibody
      responses to co-administered ovalbumin and Streptococcus mutans.
AB  - OBJECTIVE: The oral mucosa of patients undergoing dental procedures is often
      exposed to residual monomers leaking from incompletely cured acrylic resins. We
      investigated whether 2-hydroxyethyl methacrylate (HEMA) monomers applied to the
      sublingual mucosa in mice modulate the antibody responses towards co-administered
      ovalbumin (OVA) or live oral bacteria. MATERIAL AND METHODS: OVA, live mouse oral
      commensal Lactobacillus murinus or live human oral commensal Streptococcus mutans
      were administered sublingually with or without HEMA to BALB/c mice on four weekly
      occasions. One week after the last administration, the experiment was terminated
      and serum antibody levels were analyzed using ELISA. RESULTS: Significantly
      increased IgG and IgE anti-OVA antibody activity was found in the sera from mice
      immunized with OVA together with HEMA, as compared to mice immunized with OVA
      alone. Likewise, S. mutans together with HEMA induced an IgG anti-S. mutans
      antibody response that was significantly higher than the antibody response
      detected after application of S. mutans alone. No IgG anti-L. murinus antibody
      response was detected in mice immunized with L. murinus together with HEMA, as
      compared to the background activity. CONCLUSIONS: We report that HEMA monomers
      have adjuvant properties when sublingually administered in combination with OVA
      or S. mutans.

PMID- 29648492
TI  - Azacitidine effectively reduces TP53-mutant leukemic cell burden in secondary
      acute myeloid leukemia after cord blood transplantation.

PMID- 29648490
TI  - Therapeutic conserved elements (CE) DNA vaccine induces strong T-cell responses
      against highly conserved viral sequences during simian-human immunodeficiency
      virus infection.
AB  - HIV-specific T-cell responses play a key role in controlling HIV infection, and
      therapeutic vaccines for HIV that aim to improve viral control will likely need
      to improve on the T-cell responses induced by infection. However, in the setting
      of chronic infection, an effective therapeutic vaccine must overcome the enormous
      viral genetic diversity and the presence of pre-existing T-cell responses that
      are biased toward immunodominant T-cell epitopes that can readily mutate to evade
      host immunity and thus potentially provide inferior protection. To address these
      issues, we investigated a novel, epidermally administered DNA vaccine expressing
      SIV capsid (p27Gag) homologues of highly conserved elements (CE) of the HIV
      proteome in macaques experiencing chronic but controlled SHIV infection. We
      assessed the ability to boost or induce de novo T-cell responses against the
      conserved but immunologically subdominant CE epitopes. Two groups of animals were
      immunized with either the CE DNA vaccine or a full-length SIV p57gag DNA vaccine.
      Prior to vaccination, CE responses were similar in both groups. The full-length
      p57gag DNA vaccine, which contains the CE, increased overall Gag-specific
      responses but did not increase CE responses in any animals (0/4). In contrast,
      the CE DNA vaccine increased CE responses in all (4/4) vaccinated macaques. In
      SIV infected but unvaccinated macaques, those that developed stronger CE-specific
      responses during acute infection exhibited lower viral loads. We conclude that CE
      DNA vaccination can re-direct the immunodominance hierarchy towards CE in the
      setting of attenuated chronic infection and that induction of these responses by
      therapeutic vaccination may improve immune control of HIV.

PMID- 29648493
TI  - SYTAR Accepted Common Interest Community Proposals.

PMID- 29648494
TI  - Placental glucocorticoid receptor and 11beta-hydroxysteroid dehydrogenase-2
      recruitment indicates impact of prenatal adversity upon postnatal development in
      mice.
AB  - Prenatal stress may increase concentrations of maternal glucocorticoids, which
      restrict fetal growth, with variable impact upon postnatal development. Among key
      regulators of stress hormone effects are the glucocorticoid receptor (GR) and
      11beta-hydroxysteroid dehydrogenase-2 (11betaHSD2), the enzyme that inactivates
      glucocorticoid. This study utilized mice selectively bred for social dominance
      (Dom) or submissiveness (Sub), respectively exhibiting resilience or sensitivity
      to stress, to test whether stress-induced alterations in placental GR and
      11betaHSD2 protein expression may mediate divergent effects of prenatal adversity
      upon postnatal development. Pregnant Dom and Sub dams underwent prenatal
      restraint stress (PRS) for 45 min on gestational days (GD) 15-17. PRS induced a
      similar spike in serum corticosterone concentrations of dams from each strain on
      GD15 (p < .001, n = 8), and impaired fetal growth (p < .01, n = 5 litters),
      although Dom placentae were larger than Sub placentae (p < .01). Among placentae
      from Dom dams, PRS elevated protein contents of both GR (p < .05, n = 5 litters)
      and 11betaHSD2 (p < .01) on GD19. In contrast, GR contents were reduced among
      placentae from PRS-exposed Sub mice (p < .01), without changes in 11betaHSD2
      content. Correspondingly, Dom PRS pup growth recovered by PND14, yet Sub PRS pups
      remained underweight into adolescence (p < .0001, n = 40 pups). Thus, prenatal
      stress more strongly increased placental GR and 11betaHSD2 levels among Dom mice
      than in Subs. Increased GR may improve placental function and up-regulate
      11betaHSD2 expression, protecting fetuses from effects of prenatal stress upon
      postnatal development. Placental recruitment of GR and 11betaHSD2 are potential
      markers of stress-induced developmental disorders, in accordance with maternal
      resilience or sensitivity to stress.

PMID- 29648495
TI  - The S-oxidation of S-carboxymethyl-L-cysteine in hepatic cytosolic fractions from
      BTBR and phenylketonuria enu1 and enu2 mice.
AB  - Mice that were heterozygous dominant for the enu1 and enu2 mutation in
      phenylalanine monooxygenase/phenylalanine hydroxylase (PAH) resulted in hepatic
      PAH assays for S-carboxymethyl-L-cysteine (SCMC) that had significantly increased
      calculated Km (wild type (wt)/enu1, 1.84-2.12 fold increase and wt/enu2 a 2.75
      fold increase in PAH assays). The heterozygous dominant phenotypes showed a
      significantly reduced catalytic turnover of SCMC (wt/enu1, 6.11 fold decrease and
      wt/enu2 an 11.25 fold decrease in calculated Vmax). Finally, these phenotypes
      also had a significantly reduced clearance, CLE (wt/enu1, 13.02 fold and wt/enu2,
      a 30.80-30.94 fold decrease) The homozygous recessive phenotype (enu1/enu1) was
      also found to have significantly increased calculated Km (2.16 fold increase), a
      significantly reduced calculated Vmax (11.35-12.33 fold decrease) and CLE (24.75
      25.00 fold decrease). The enu2/enu2, homozygous recessive phenotype had no
      detectable PAH activity using SCMC as substrate. The identity of the enzyme
      responsible for the C-oxidation of L-phenylalanine (L-Phe) and the S-oxidation of
      SCMC in wt/wt (BTBR) mice was identified using monoclonal antibody and selective
      chemical inhibitors and was found to be PAH. This in vitro mouse hepatic
      cytosolic fraction metabolism investigation provides further evidence to support
      the hypothesis that an individual possessing one variant allele for PAH will
      result in a poor metaboliser phenotype that is unable to produce significant
      amounts of S-oxide metabolites of SCMC.

PMID- 29648496
TI  - The Wisdom of Thai Indigenous Healers for the Spiritual Healing of Fractures.
AB  - AIMS: The aim of this study was to explore the wisdom of Thai indigenous healers
      (IHs) for physical and spiritual healing and their treatment process for
      fractures. METHOD: Twelve IHs from four regions of Thailand were selected using
      cluster and purposive sampling. They were interviewed on their methods for
      treating fractures. The Colaizzi method was used for analysis, and we returned to
      the IHs for validity confirmation. FINDINGS: The wisdom of IHs is believed to be
      inherited from ancestors and from a "sixth sense," their former teacher's spirit.
      There are no textbooks, only one-on-one training. The annual Wai Khru ceremony,
      where IHs pay respect to their teachers, is believed to also impart a blessing of
      greater wisdom to the student healer. Their physical treatment of fractures is
      like that by an orthopedic physician, but their methods and materials are
      different because physical treatment is combined with spiritual care. CONCLUSION:
      Certain aspects of IH practice may have application for professional nursing. It
      is suggested that incorporating traditional spiritual care into nursing may
      improve patients' quality of life, both physically and spiritually.

PMID- 29648497
TI  - Low reproducibility between oral radiologists and general dentists with regards
      to radiographic diagnosis of caries.
AB  - AIM: Early clinical and radiological diagnosis of dental caries is one of the
      fundamental objectives of clinical dentistry because of the high frequency of the
      disease and severe complications if caries remains untreated, especially among
      the elderly and patients with immunodeficiency. Dental panoramic tomography (DPT)
      is a common radiographic method for evaluating dentition when indicated,
      especially in an adult population. The aim of this study was to assess the
      reproducibility of diagnosis between specialists in oral radiology and general
      dentists with regards to caries lesions based on DPTs of adults. MATERIAL AND
      METHODS: One-hundred DPTs taken from adult patients (average age 35) and then
      analyzed and reported on by 42 general dentists were then analyzed independently
      by two specialists in oral radiology with respect to caries lesions in the
      premolar and molar areas using radiographic criteria established for caries
      diagnosis. The general dentists versus oral radiologists were not calibrated
      before. Level of agreement between specialists and general dentists was measured
      using Cohen's kappa. RESULTS: Comparison between observations of general dentists
      and specialists in oral radiology showed that 61% of the caries lesions on
      proximal surfaces of premolars and molars observed by specialists went unobserved
      by general dentists. Cohen's kappa value for specialists was 0.85 (p < .001) and
      for each specialist and general dentists 0.48 (p < .001) and 0.44 (p < .001).
      CONCLUSIONS: The reproducibility between specialists in oral radiology and
      general dentists for detecting caries in DPTs was low.

PMID- 29648498
TI  - Timing matters: the interval between acute stressors within chronic mild stress
      modifies behavioral and physiologic stress responses in male rats.
AB  - Chronic mild stress can lead to negative health outcomes. Frequency, duration,
      and intensity of acute stressors can affect health-related processes. We tested
      whether the temporal pattern of daily acute stressors (clustered or dispersed
      across the day) affects depression-related physiology. We used a rodent model to
      keep stressor frequency, duration, and intensity constant, and experimentally
      manipulated the temporal pattern of acute stressors delivered during the active
      phase of the day. Adult male Sprague-Dawley rats were exposed to one of three
      chronic mild stress groups: Clustered: stressors that occurred within 1 hour of
      each other (n = 21), Dispersed: stressors that were spread out across the active
      phase (n = 21), and Control: no stressors presented (n = 21). Acute mild
      stressors included noise, strobe lights, novel cage, cage tilt, wet bedding, and
      water immersion. Depression-related outcomes included: sucrose preference, body
      weight, circulating glucocorticoid (corticosterone) concentration after a novel
      acute stressor and during basal morning and evening times, and endotoxin-induced
      circulating interleukin-6 concentrations. Compared to control rats, those in the
      Clustered group gained less weight, consumed less sucrose, had a blunted acute
      corticosterone response, and an accentuated acute interleukin-6 response. Rats in
      the Dispersed group had an attenuated corticosterone decline during the active
      period and after an acute stressor compared to the Control group. During a
      chronic mild stress experience, the temporal distribution of daily acute
      stressors affected health-related physiologic processes. Regular exposure to
      daily stressors in rapid succession may predict more depression-related symptoms,
      whereas exposure to stressors dispersed throughout the day may predict diminished
      glucocorticoid negative feedback.

PMID- 29648499
TI  - Burnout among pilots: psychosocial factors related to happiness and performance
      at simulator training.
AB  - In this study among airline pilots, we aim to uncover the work characteristics
      (job demands and resources) and the outcomes (job crafting, happiness and
      simulator training performance) that are related to burnout for this occupational
      group. Using a large sample of airline pilots, we showed that 40% of the
      participating pilots experience high burnout. In line with Job Demands-Resources
      theory, job demands were detrimental for simulator training performance because
      they made pilots more exhausted and less able to craft their job, whereas job
      resources had a favourable effect because they reduced feelings of disengagement
      and increased job crafting. Moreover, burnout was negatively related to pilots'
      happiness with life. These findings highlight the importance of psychosocial
      factors and health for valuable outcomes for both pilots and airlines.
      Practitioner Summary: Using an online survey among the members of a European
      pilots' professional association, we examined the relationship between
      psychosocial factors (work characteristics, burnout) and outcomes (simulator
      training performance, happiness). Forty per cent of the participating pilots
      experience high burnout. Job demands were detrimental, whereas job resources were
      favourable for simulator training performance/happiness. Twitter text: 40% of
      airline pilots experience burnout and psychosocial work factors and burnout
      relate to performance at pilots' simulator training.

PMID- 29648500
TI  - The link between depression and performance on the Symbol Digit Modalities Test:
      Mechanisms and clinical significance.
AB  - OBJECTIVE: To determine the mechanism and clinical significance of depression
      related differences in performance on the Symbol Digit Modalities Test (SDMT).
      METHODS: The influence of depression on two versions of a computerized SDMT (i.e.
      fixed versus variable code) was assessed. Both versions involve processing speed,
      but the fixed c-SDMT also encompasses incidental visual memory. RESULTS:
      Depression was associated with a 19.06% slowing on the variable ( p = 0.002) and
      an 8.10% slowing on the fixed ( p = 0.219) c-SDMT. CONCLUSION: Depression
      associated differences in performance on the SDMT appear linked more to a
      reduction in processing speed than a decline in incidental visual memory and
      exceed the 10% threshold considered clinically significant.

PMID- 29648501
TI  - New versus old: Implications of evolving diagnostic criteria for relapsing
      remitting multiple sclerosis.
AB  - The International Panel on Diagnosis of Multiple Sclerosis (MS) recently revised
      the 2010 McDonald criteria and made recommendations for revision, allowing for
      the earliest possible, accurate diagnosis of MS. For relapsing-remitting MS,
      positive, unmatched cerebrospinal fluid oligoclonal bands may substitute for
      dissemination in time. Symptomatic lesions, including brainstem and spinal cord,
      may demonstrate dissemination in space or in time if enhancing (with the
      exception of the optic nerve). Cortical and juxtacortical lesions are equivalent.
      In this retrospective analysis, we applied revised criteria to 250 patients
      previously diagnosed with relapsing-remitting MS according to 2010 criteria and
      assessed for change in diagnostic times. There was a significant improvement in
      time to diagnosis between 2010 and 2017 groups ( p < 0.01). Median time to
      diagnosis according to McDonald 2010 was 7.4 months, compared with 2.3 months for
      McDonald 2017. Use of cerebrospinal fluid results most frequently resulted in a
      reduction in time to diagnosis. Symptomatic gadolinium-enhancing lesions led to
      earliest diagnostic times.

PMID- 29648502
TI  - Social Desirability in Spouse Ratings.
AB  - Whether or not socially desirable responding is a cause for concern in
      personality assessment has long been debated. For many researchers, McCrae and
      Costa laid the issue to rest when they showed that correcting for socially
      desirable responding in self-reports did not improve the agreement with spouse
      ratings on the Neuroticism, Extraversion, and Openness to Experience Personality
      Inventory. However, their findings rest on the assumption that observer ratings
      in general, and spouse ratings in particular, are an unbiased external criterion.
      If spouse ratings are also susceptible to socially desirable responding,
      correcting for the bias in self-rated measures cannot be assumed to increase
      agreement between self-reports and spouse ratings, and thus failure to do so
      should not be taken as evidence for the ineffectiveness of measuring and
      correcting for socially desirable responding. In the present study, McCrae and
      Costa's influential study was replicated with the exception of measuring socially
      desirable responding with the Marlowe-Crowne Social Desirability Scale, in both
      self-reports and spouse ratings. Analyses were based on responses from 70 couples
      who had lived together for at least one year. The results showed that both self
      reports and spouse ratings are susceptible to socially desirable responding and
      thus McCrae and Costa's conclusion is drawn into question.

PMID- 29648504
TI  - Creating energy citizenship through material participation.
AB  - Transitions towards low-carbon energy systems will be comprehensive and
      demanding, requiring substantial public support. One important contribution from
      STS is to highlight the roles of citizens and public engagement. Until recently,
      energy users have often been treated as customers and passive market actors, or
      as recipients of technology at the margins of centralized systems. With respect
      to the latter role, critical or hesitant public action has been explained in
      terms of NIMBYism and knowledge deficits. This article focuses on the production
      of energy citizenship when considering public participation in low-carbon energy
      transitions. We draw upon the theory of 'material participation' to highlight how
      introducing and using emergent energy technologies may create new energy
      practices. We analyze an ongoing introduction of new material objects,
      highlighting the way these technologies can be seen as material interventions co
      constructing temporalities of new and sustainable practices. We argue that
      artefacts such as the electric car, the smart meter and photovoltaic panels may
      become objects of participation and engagement, and that the introduction of such
      technologies may foster material participation and energy citizenship. The paper
      concludes with a discussion about the role of policies for low-carbon energy
      transitions on the making of energy citizenship, as well as limits of introducing
      a materially based energy citizenship.

PMID- 29648505
TI  - Abstracts From the 5th Annual Congress on Medicine & Science in Ultra-Endurance
      Sports, May 9-10, 2018, Castello de la Plana, Spain.

PMID- 29648503
TI  - Brazilian medicinal plants with corroborated anti-inflammatory activities: a
      review.
AB  - CONTEXT: Inflammatory disorders are common in modern life, and medicinal plants
      provide an interesting source for new compounds bearing anti-inflammatory
      properties. In this regard, Brazilian medicinal plants are considered to be a
      promising supply of such compounds due to their great biodiversity. OBJECTIVES:
      To undertake a review on Brazilian medicinal plants with corroborated anti
      inflammatory activities by selecting data from the literature reporting the
      efficacy of plants used in folk medicine as anti-inflammatory, including the
      mechanisms of action of their extracts and isolated compounds. METHODS: A search
      in the literature was undertaken by using the following Web tools: Web of
      Science, SciFinder, Pub-Med and Science Direct. The terms 'anti-inflammatory' and
      'Brazilian medicinal plants' were used as keywords in search engine. Tropicos and
      Reflora websites were used to verify the origin of the plants, and only the
      native plants of Brazil were included in this review. The publications reporting
      the use of well-accepted scientific protocols to corroborate the anti
      inflammatory activities of Brazilian medicinal plants with anti-inflammatory
      potential were considered. RESULTS: We selected 70 Brazilian medicinal plants
      with anti-inflammatory activity. The plants were grouped according to their anti
      inflammatory mechanisms of action. The main mechanisms involved inflammatory
      mediators, such as interleukins (ILs), nuclear factor kappa B (NF-kappaB),
      prostaglandin E2 (PGE2), cyclooxygenase (COX) and reactive oxygen species (ROS).
      CONCLUSIONS: The collected data on Brazilian medicinal plants, in the form of
      crude extract and/or isolated compounds, showed significant anti-inflammatory
      activities involving different mechanisms of action, indicating Brazilian plants
      as an important source of anti-inflammatory compounds.

PMID- 29648508
TI  - Avoiding bias in trials in which allocation ratio is varied.

PMID- 29648509
TI  - Time to regenerate: the doctor in the age of artificial intelligence.

PMID- 29648506
TI  - Systemic equid alphaherpesvirus 9 in a Grant's zebra.
AB  - A 2-y-old female Grant's zebra ( Equus quagga [ burchellii] boehmi) was presented
      with a clinical history of depression, anorexia, and weakness of 1-wk duration.
      Postmortem examination identified ulcers on the tongue and palate; a large
      abscess adjacent to the larynx; left lung consolidation; mild swelling,
      darkening, and congestion of the liver with accentuation of the lobular pattern;
      and edema and congestion of the distal small and large intestines. Histologic
      examination identified necrotizing bronchopneumonia, necrotizing hepatitis,
      nephritis, and enterocolitis. Eosinophilic intranuclear inclusions were detected
      in syncytial cells and degenerate bronchial epithelium in the lungs and in some
      hepatocytes associated with necrotic foci. Bacterial cultures of the lung, liver,
      and laryngeal abscess failed to detect any significant pathogen. Lung and liver
      tested positive for equine herpesvirus with neuropathogenic marker by real-time
      PCR. Subsequently, equine herpesvirus was isolated in tissue culture, and the
      entire viral DNA polymerase gene (ORF30) was sequenced. The zebra lung isolate
      had a very close nucleotide and amino acid sequence identity to equid
      alphaherpesvirus 9 (EHV-9; 99.6% and 99.8%, respectively) in contrast to the
      neuropathogenic T953 strain of EHV-1 (94.7% and 96.6%, respectively). Although
      zebras are considered the natural host for EHV-9, we document an unusual acute
      systemic, fatal EHV-9 infection in a 2-y-old Grant's zebra.

PMID- 29648510
TI  - A doctor who regenerates.

PMID- 29648512
TI  - Malignant ureteric obstruction decompression: how much gain for how much pain? A
      narrative review.
AB  - Over the last thirty years, the management of Malignant Ureteric Obstruction
      (MUO) has evolved from a single disciplinary decision to a multi-disciplinary
      approach. Careful consideration must be given to the risks and benefits of
      decompression of hydronephrosis for an individual patient. There is a lack of
      consensus of opinion as well as strong evidence to support the decision process.
      Outcomes that were identified amongst patients undergoing treatment for MUO
      included prognosis, quality of life (QOL), complications, morbidity and
      prognostication tools. A total of 63 papers were included. Median survival was
      6.4 months in the 53 papers that stated this outcome. Significant predictors to
      poor outcomes included low serum albumin, hyponatremia, the number of malignancy
      related events, and performance status of 2 or worse on the European cooperative
      cancer group. We propose a multi-centre review of outcomes to enable evidence
      based consultations for patients and their families.

PMID- 29648514
TI  - Beneficial impacts of regular exercise on platelet function in sedentary older
      adults: evidence from a randomized 6-mo walking trial.
AB  - Platelet activation, including the formation of monocyte platelet aggregates
      (MPAs), contributes to atherosclerosis, thrombus formation, and acute coronary
      syndromes. Regular participation in exercise can lower cardiovascular risk, but
      little is known regarding the impact of exercise training on platelet function.
      We investigated the effect of 6 mo of walking exercise on platelet function in
      sedentary older adults without significant cardiovascular disease. Twenty-seven
      participants were randomly allocated to 6 mo of either: no-exercise ( n = 13) or
      3 * 50 min/wk of supervised center-based walking ( n = 14). Circulating and
      agonist-induced MPAs were assessed using flow cytometry before [ month 0 (0M)]
      and after [ month 6 (6M)] the intervention. Circulating MPAs increased from 0M
      (3.7 +/- 1.0%) to 6M (4.7 +/- 1.6%) in the no-exercise group ( P = 0.009),
      whereas a nonsignificant decrease was observed in the walking group (0M 4.3 +/-
      1.7 vs. 6M 3.7 +/- 1.2 %, P = 0.052). The change in MPAs between groups was
      significant ( P = 0.001). There were no differences between groups in platelet
      responses to agonists across the interventions (all P > 0.05). Collectively,
      these data suggest that the absence of regular exercise may increase MPAs, which
      are cellular mediators involved in atherosclerosis, while regular walking
      inhibits such increases. The thrombotic function of platelets appears to be
      relatively unaltered by exercise training. This study provides novel data related
      to the cardioprotective effects associated with participation in exercise. NEW &
      NOTEWORTHY Monocyte-platelet aggregates contribute to atherosclerosis and
      exercise can lower cardiovascular risk. This is the first study to discover that
      a lack of regular physical activity is associated with increased monocyte
      platelet aggregates over a 6-mo intervention period. In contrast, walking
      exercise inhibits increased monocyte-platelet aggregates in the circulation. This
      study highlights a novel pathway by which regular participation in exercise
      exerts its cardioprotective effects.

PMID- 29648515
TI  - Peripheral revascularization attenuates the exercise pressor reflex and increases
      coronary exercise hyperemia in peripheral arterial disease.
AB  - Peripheral arterial disease (PAD) is associated with augmented blood pressure
      (BP) and impaired coronary blood flow responses to exercise, which may increase
      cardiovascular risk. We investigated the effects of leg revascularization on the
      BP and coronary blood flow responses to exercise in PAD. Seventeen PAD patients
      (11 men, 66 +/- 2 yr) performed single-leg plantar flexion exercise 24 h before
      and 1 mo following leg revascularization. BP and heart rate (HR) were measured
      continuously, and rate pressure product (systolic BP * HR) was calculated as an
      index of myocardial oxygen demand. Coronary blood velocity was obtained by
      transthoracic Doppler echocardiography in 8/17 subjects. The mean BP response to
      plantar flexion exercise was attenuated by leg revascularization (pre
      revascularization: 15 +/- 4 vs. post-revascularization: 7 +/- 3 mmHg, P = 0.025).
      The HR response to plantar flexion was also attenuated following leg
      revascularization (pre-revascularization: 9 +/- 1 vs. post-revascularization: 6
      +/- 1 beats/min, P = 0.006). The change in coronary blood velocity with exercise
      was greater at the post-revascularization visit: 4 +/- 1 vs. pre
      revascularization: -1 +/- 2 cm/s ( P = 0.038), even though the change in rate
      pressure product was not greater following revascularization in these subjects
      (pre-revascularization: 2,796 +/- 871 vs. post-revascularization: 1,766 +/- 378
      mmHg.beats/min, P = 0.082). These data suggest that leg revascularization alters
      reflex control of BP, HR, and coronary blood flow in response to exercise in
      patients with PAD. NEW & NOTEWORTHY We found that peripheral revascularization
      procedures lowered exercise blood pressure and improved coronary blood flow in
      patients with peripheral arterial disease.

PMID- 29648516
TI  - The phosphodiesterase-4 inhibitor roflumilast reverts proteolysis in skeletal
      muscle cells of patients with COPD cachexia.
AB  - Peripheral muscle weakness and mass loss are characteristic features in severe
      chronic obstructive pulmonary disease (COPD). We hypothesized that the
      phosphodiesterase (PDE)-4 inhibitor roflumilast-induced cAMP may ameliorate
      proteolysis and metabolism in skeletal muscles of COPD patients with severe
      muscle wasting. In myogenic precursor cells (isolated from muscle biopsies and
      cultured up to obtain differentiated myotubes) from 10 severe COPD patients and
      10 healthy controls, which were treated with 1 MUM roflumilast N-oxide (RNO) for
      three time cohorts (1, 6, and 24 h), genes of antioxidant defense and oxidative
      stress marker, myogenesis and muscle metabolism, proteolysis (tyrosine release
      assay) and ubiquitin-proteasome system markers, autophagy, and myosin isoforms
      were analyzed using RT-PCR and immunoblotting. In COPD patients at 6 h RNO
      treatment, myotube tyrosine release, total protein ubiquitination, and tripartite
      motif-containing protein 32 levels were significantly lower than healthy
      controls, whereas at 24 h RNO treatment, myotube myosin heavy chain ( MyHC) -I
      and MyHC-IIx expression levels were upregulated in both patients and controls. In
      the 6-h RNO cohort, in patients and controls, myotube expression of nuclear
      factor (erythroid-derived 2)-like 2 ( NRF2) and its downstream antioxidants
      sirtuin-1, FGF-inducible 14, and insulin-like growth factor-1 was upregulated,
      whereas that of myocyte-specific enhancer factor 2C, myogenic differentiation,
      myogenin, myostatin, atrogin-1, and muscle RING-finger protein-1 was
      downregulated. In myotubes of severe COPD patients with cachexia, roflumilast
      induced cAMP signaling exerts beneficial effects by targeting muscle protein
      breakdown (tyrosine release), along with reduced expression of proteolytic
      markers of the ubiquitin-proteasome system and that of myostatin. In both
      patients and controls, roflumilast also favored antioxidant defense through
      upregulation of the NRF2 pathway and that of the histone deacetylase sirtuin-1,
      whereas it improved the expression of slow- and fast-twitch myosin isoforms.
      These findings show that muscle dysfunction and wasting may be targeted by
      roflumilast-induced cAMP signaling in COPD. These results have potential
      therapeutic implications, as this PDE-4 inhibitor is currently available for the
      treatment of systemic inflammation and exacerbations in patients with severe
      COPD. NEW & NOTEWORTHY In myotubes of cachectic chronic obstructive pulmonary
      disease (COPD) patients, cAMP signaling exerted beneficial effects by targeting
      muscle proteolysis and reducing gene expression of proteolytic markers of the
      ubiquitin-proteasome system and that of myostatin. In myotubes of patients and
      controls, roflumilast also favored antioxidant defense through upregulation of
      the nuclear factor (erythroid-derived 2)-like 2 pathway, of sirtuin-1, and of
      gene expression of slow- and fast-twitch isoforms. These findings have potential
      clinical implications for the treatment of muscle wasting in patients with COPD
      and cachexia.

PMID- 29648517
TI  - Preliminary evidence of reductive stress in human cytotoxic T cells following
      exercise.
AB  - This study investigated immunophenotypic differences in intracellular thiol redox
      state of peripheral blood mononuclear cells (PBMCs) isolated from trained [ n =
      9, means +/- SD: age 28 +/- 5 yr; (body mass index) BMI 23.2 +/- 2.6 kg/m2;
      Vo2max (maximal oxygen intake)56.9 +/- 6.1 ml.kg-1.min-1] and recreationally
      active (RA, n = 11, means +/- SD: age 27 +/- 6 yr; BMI 24.2 +/- 3.7 kg/m2; Vo2max
      45.1 +/- 6.4 ml.kg-1.min-1) participants before and after a maximal aerobic
      exercise tolerance test. Blood samples were taken before (Pre), during (sample
      acquired at 70% maximum heart rate), immediately after (Post + 0), and 15 min
      postexercise (Post + 15). PBMCs were isolated, and reduced thiol analysis
      [fluorescein-5 maleimide (F5M)] by immunophenotype [cluster of differentiation
      (CD)3+, CD4+, and CD8+] was performed using flow cytometry. A significant
      increase in cellular F5M fluorescence was observed in CD3+ T cells at Post + 0,
      with changes driven to a greater extent by CD8+ T cells (fold change in both
      groups CD4: +2.3, CD8: +2.8; P < 0.05). Further analysis revealed a population of
      highly reduced CD8+ T cells (CD8+T-reduced+) that significantly increased from
      Pre to Post + 0 in RA participants only (RA: +272 cell/ul, P < 0.05). To
      understand these results further, CD8+T-reduced+ and CD8+T-reduced- cells were
      analyzed for immunophenotype in response to the same exercise protocol ( n = 6,
      means +/- SD: age 24 +/- 5 yr; BMI 25.7 +/- 4.1 kg.m-2; Vo2max 41.33 +/- 7.63
      ml.kg-1.min-1). CD8+T-reduced+ had significantly less lymphoid homing potential
      (chemokine receptor type 7) Post + 0 compared with Pre. This study is the first,
      to our knowledge, to demonstrate that lymphocyte populations become more
      reductive in response to acute exercise. NEW & NOTEWORTHY The study presented
      provides the first evidence to suggest that cytotoxic T cells become transiently
      reductive in healthy individuals following a single bout of cycling. Detection of
      these cells was enabled via the use of a flow cytometric assay that incorporates
      the thiol reactive probe fluorescein-5 maleimide. Using this method, transient
      reductive stress in viable T cells is permissible and provides the basis for
      further research in the area of exercise immunology.

PMID- 29648518
TI  - Heritability of major components of proprioception.

PMID- 29648519
TI  - Glutamate dehydrogenase: role in regulating metabolism and insulin release in
      pancreatic beta-cells.
AB  - Regulation of insulin release and glucose homeostasis by pancreatic beta-cells is
      dependent on the metabolism of glucose by glucokinase (GK) and the influence of
      that activity on oxidative phosphorylation. Genetic alterations that result in
      hyperactivity of mitochondrial glutamate dehydrogenase (GDH-1) can cause
      hypoglycemia-hyperammonemia following high protein meals, but the role of GDH-1
      remains poorly understood. GDH-1 activity is strongly inhibited by GTP, to near
      zero in the absence of ADP, and cooperatively activated ( n = 2.3) by ADP. The
      dissociation constant for ADP is near 200 uM in vivo, but leucine and its
      nonmetabolized analog 2-amino-2-norbornane-carboxylic acid (BCH) can activate GDH
      1 by increasing the affinity for ADP. Under physiological conditions, as [ADP]
      increases GDH-1 activity remains very low until ~35 uM (threshold) and then
      increases rapidly. A model for GDH-1 and its regulation has been combined with a
      previously published model for glucose sensing that coupled GK activity and
      oxidative phosphorylation. The combined model (GK-GDH-core) shows that GK
      activity determines the energy state ([ATP]/[ADP][Pi]) in beta-cells for glucose
      concentrations > 5 mM ([ADP] < 35 uM). As glucose falls < 5 mM the [ADP]
      dependent increase in GDH-1 activity prevents [ADP] from rising above ~70 uM.
      Thus, GDH-1 dynamically buffers beta-cell energy metabolism during hypoglycemia,
      maintaining the energy state and the basal rate of insulin release. GDH-1
      hyperactivity suppresses the normal increase in [ADP] in hypoglycemia. This leads
      to hypoglycemia following a high protein meal by increasing the basal rate of
      insulin release (beta-cells) and decreasing glucagon release (alpha-cells). NEW &
      NOTEWORTHY A model of beta-cell metabolism and regulation of insulin release is
      presented. The model integrates regulation of oxidative phosphorylation,
      glucokinase (GK), and glutamate dehydrogenase (GDH-1). GDH-1 is near equilibrium
      under physiological conditions, but the activity is inhibited by GTP. In
      hypoglycemia, however, GK activity is low and [ADP], a potent activator of GDH-1,
      increases. Reducing equivalents from GDH dynamically buffers the
      intramitochondrial [NADH]/[NAD+], and thereby the energy state, preventing
      hypoglycemia-induced substrate deprivation.

PMID- 29648520
TI  - Transfer coefficients better reflect emphysematous changes than carbon monoxide
      diffusing capacity in obstructive lung diseases.
AB  - The overlap between asthma and chronic obstructive pulmonary disease (COPD) has
      attracted the interest of pulmonary physicians; thus, measurement of carbon
      monoxide diffusion capacity (DLco) and/or transfer coefficients (Kco, DLco/VA)
      may become valuable in clinical settings. How these parameters behave in chronic
      obstructive lung diseases is poorly understood. We predicted that Kco might more
      accurately reflect emphysematous changes in the lungs than DLco. We examined DLco
      and Kco in nonsmokers and smokers with asthma and investigated their
      relationships with forced expiratory volume in 1 s (%FEV1) by group. We then
      selected nonsmokers (As-NS) and smokers with asthma (As-Sm) in both groups and
      those with COPD while controlling for the degree of airflow limitation across
      groups. Emphysema volumes [%lung attenuation volume (%LAV)] and percentage of
      cross-sectional area of small pulmonary vessels <5 mm2 (%CSA<5) were measured by
      computed tomography. In As-NS, %Kco was significantly higher when FEV1% was
      reduced, but such a correlation was not seen in As-Sm. %Kco successfully
      differentiated among the three groups when airflow limitation levels were
      matched. However, %DLc, was significantly reduced only in patients with COPD.
      Both %LAV and %CSA<5 were better correlated with %Kco than with %DLco. There was
      discordance between %DLCO and %Kco in As-Sm, which was not seen in As-NS.
      Overall, %Kco better reflects emphysematous changes in obstructive lung diseases
      than %DLco. NEW & NOTEWORTHY Despite differing behaviors of %Kco and %DLco in
      several diseases, the characteristics of these parameters have not been fully
      examined in smokers with asthma. Here, we demonstrated that %Kco is a more
      sensitive parameter of pathophysiology, better reflecting emphysematous changes
      in chronic obstructive lung diseases overall, compared with %DLco. Thus, more
      precise interpretations of %DLco and %Kco may provide clues for understanding the
      pathophysiology of obstructive lung diseases.

PMID- 29648521
TI  - Understanding Angiogenesis During Aging: Opportunities for Discoveries and New
      Models.
AB  - Microvascular network growth and remodeling are common denominators for most age
      related pathologies. For multiple pathologies (myocardial infarction, stroke,
      hypertension) promoting microvascular growth, termed angiogenesis, would be
      beneficial. For others (cancer, retinopathies, rheumatoid arthritis) blocking
      angiogenesis would be desirable. Most therapeutic strategies, however, are
      motivated based on studies using adult animal models. This approach is
      problematic and does not account for the impaired angiogenesis and the inherent
      network structure changes that might result from age. Considering the common
      conception that angiogenesis is impaired with age, a need exists to identify the
      causes and mechanisms of angiogenesis in aged scenarios, and for new tools to
      enable comparison of aged versus adult responses to therapy. The objective of
      this article will be to introduce opportunities for advancing our understanding
      of angiogenesis in aging through the discovery of novel cell changes along aged
      microvascular networks and the development of novel ex vivo models.

PMID- 29648523
TI  - Feasibility and costs of a targeted cholera vaccination campaign in Ethiopia.
AB  - ShancholTM, a WHO-prequalified oral cholera vaccine (OCV), has been used to
      control endemic cholera in Asia, as well as in emergencies and outbreaks
      elsewhere. The vaccine has not been used by public health systems in cholera
      endemic settings of Africa although several outbreak response campaigns have been
      conducted. Here we present experiences from a mass vaccination campaign in a
      cholera-endemic setting of Ethiopia in which ShancholTM was introduced through
      the public health system. The vaccination site was selected based on cholera
      cases reported in previous years. Social mobilization involved sensitization of
      community leaders, household visits, and mass distribution of banners, posters
      and leaflets. The vaccination was implemented after careful microplanning of
      logistics and cold chain, manpower, transportation, vaccine supply and
      supervision and monitoring of adverse events. Vaccine administration was recorded
      on individual vaccination cards. Vaccine delivery costs were collected and
      analyzed after vaccination. As there was no experience with ShancholTM in
      Ethiopia, a bridging trial was conducted to demonstrate safety and immunogenicity
      of the vaccine in the local population prior to the mass vaccination. Oral
      cholera vaccination was conducted in two rounds of four days each in February
      2015 and March 2015 in 10 selected villages of Shashemenae rural district of
      Ethiopia. A total of 62,161 people targeted. 47,137 people (76%) received the
      first dose, and 40,707 (65%) received two doses. The financial cost of the
      vaccination campaign was estimated at US $2.60 per dose or US $5.64 per fully
      immunized person. The cost of vaccine delivery excluding vaccine procurement was
      $0.68 per dose or $1.48 per fully immunized person. The study demonstrates that
      mass cholera vaccination administered through the public health system in
      Ethiopia is feasible, can be implemented through the existing health system at an
      affordable cost, and the vaccine is acceptable to the community. The lessons from
      this study are useful for deploying OCV in other African endemic settings through
      the public health system and may guide future immunization policy decisions.

PMID- 29648522
TI  - Impact of recurrent laryngeal nerve lesion on oropharyngeal muscle activity and
      sensorimotor integration in an infant pig model.
AB  - The successful performance of a swallow requires dynamic integration between a
      wide range of sensory inputs and muscle activities to produce the coordinated
      kinematics of oropharyngeal structures. Damage to the recurrent laryngeal nerve
      (RLN) produces dysphagia in infants, with food or liquid entering the airway
      despite this nerve having minimal direct sensory or motor connections to the act
      of swallowing, apart from vocal fold closure. Previous results have demonstrated
      that a complete RLN lesion disrupts both performance and kinematics before
      initiation of the pharyngeal swallow in infants. We tested the hypothesis that a
      RLN lesion produces changes in the normal activity of oral floor, tongue, and
      infrahyoid muscles during a swallow. We recorded swallowing in our validated
      infant pig model, with synchronous high-speed imaging and fine-wire, chronic
      electromyography. We found changes in the timing, duration, and amplitude of the
      motor pattern in an array of muscles that are supplied by several different
      cranial and cervical nerves. Some of these changes in muscle activity are
      associated with the preparatory aspects of bolus aggregation or movement and so
      occur before the pharyngeal swallow. Taken with previous biomechanical results,
      these patterns suggest an intricate brain stem sensorimotor integration that
      occurs as part of a swallow. In particular, the execution of oral motor function
      is changed as a result of this simple lesion. NEW & NOTEWORTHY Damage to the
      recurrent laryngeal nerve compromises swallowing despite an absent or minimal
      contribution to either the motor or sensory aspects of this function. This study
      documents EMG changes, following RLN lesion, to non-RLN innervated muscles that
      are active during swallowing in an infant model. Some of these muscles fire
      before the pharyngeal swallow and are associated with the preparatory aspects of
      bolus aggregation and movement, suggesting important sensorimotor integration at
      a brain stem level.

PMID- 29648525
TI  - Foreword: The Year in Review: Comments on Plants, Cyclodextrins, Microbiota, and
      Diabetes.

PMID- 29648524
TI  - Preface: The Wealth of microRNA Kingdom: From Plant Defense to Cancer Prevention.

PMID- 29648526
TI  - Fluviicola kyonggii sp. nov., a bacterium isolated from forest soil and emended
      description of the genus Fluviicola.
AB  - A novel bacterium, designated strain CA-1T, was isolated from forest soil in
      Kyonggi University. Cells were strictly aerobic, Gram-stain-negative, catalase
      positive, oxidase-negative, non-motile, non-spore-forming, rod-shaped and red
      orange-pigmented. Strain CA-1T hydrolysed casein and DNA. It was able to grow at
      15-37  degrees C, pH 5.5-9.0 and at 0-2 % (w/v) NaCl concentration. Flexirubin
      type pigments were present. Phylogenetic analysis based on its 16S rRNA gene
      sequence indicated that strain CA-1T formed a lineage within the family
      Crocinitomicaceae of the phylum Bacteroidetes that was distinct from Fluviicola
      hefeinensis MYL-8T (96.8 % sequence similarity) and Fluviicola taffensis DSM
      16823T (96.1 %). Strain CA-1T contained menaquinone-6 as a sole respiratory
      quinone. The major polar lipids were phosphatidylethanolamine, unidentified
      aminolipids, an unidentified aminophospholipid and an unidentified lipid. The
      major cellular fatty acids were iso-C15 : 0, iso-C17 : 0 3-OH, C15 : 0 2-OH,
      summed feature 3 (C16 : 1omega7c and/or C16 : 1omega6c) and iso-C15 : 1 G. The
      DNA G+C content of strain CA-1T was 44.1 mol%. The polyphasic characterization
      revealed that strain CA-1T represents a novel species in the genus Fluviicola,
      for which the name Fluviicola kyonggii sp. nov. is proposed. The type strain is
      CA-1T (=KEMB 9005-526T=KACC 19148T=NBRC 112684T).

PMID- 29648527
TI  - Streptomyces manganisoli sp. nov., a novel actinomycete isolated from manganese
      contaminated soil.
AB  - A novel actinomycete isolate, designated strain MK44T, was isolated from a
      Manganese-polluted soil sample collected near Xiangtan Manganese Mine, South
      Central China and subjected to a polyphasic taxonomic characterization.
      Comparison of 16S rRNA gene sequences showed that strain MK44T was a member of
      the genus Streptomyces and most closely related to Streptomyces specialis JCM
      16611T (97.9 %) and Streptomyces mayteni JCM 16957T (97.4 %). The DNA-DNA
      relatedness between strain MK44T and the above two related type species were
      30.9+/-0.3 and 29.9+/-3.5 %, respectively, values which are far lower than the 70
      % threshold for the delineation of a novel prokaryotic species. Furthermore, the
      results of physiological, biochemical and chemotaxonomic tests allowed further
      phenotypic differentiation. Therefore, it is concluded that strain MK44T
      represents a novel species of the genus Streptomyces, for which the name
      Streptomyces manganisoli sp. nov. is proposed. The type strain is MK44T (=GDMCC
      4.137T=KCTC 39920T).

PMID- 29648528
TI  - Lactobacillus micheneri sp. nov., Lactobacillus timberlakei sp. nov. and
      Lactobacillus quenuiae sp. nov., lactic acid bacteria isolated from wild bees and
      flowers.
AB  - Gram-stain-positive, rod-shaped, non-spore forming bacteria have been isolated
      from flowers and the guts of adult wild bees in the families Megachilidae and
      Halictidae. Phylogenetic analysis of the 16S rRNA gene indicated that these
      bacteria belong to the genus Lactobacillus, and are most closely related to the
      honey-bee associated bacteria Lactobacillus kunkeei (97.0 % sequence similarity)
      and Lactobacillus apinorum (97.0 % sequence similarity). Phylogenetic analyses of
      16S rRNA genes and six single-copy protein coding genes, in situ and in silico
      DNA-DNA hybridization, and fatty-acid profiling differentiates the newly isolated
      bacteria as three novel Lactobacillus species: Lactobacillus micheneri sp. nov.
      with the type strain Hlig3T (=DSM 104126T,=NRRL B-65473T), Lactobacillus
      timberlakei with the type strain HV_12T (=DSM 104128T,=NRRL B-65472T), and
      Lactobacillus quenuiae sp. nov. with the type strain HV_6T (=DSM 104127T,=NRRL B
      65474T).

PMID- 29648529
TI  - Gram-negative bloodstream infections in hemodialysis patients: A retrospective
      study?.
AB  - BACKGROUND: Bloodstream infections (BSIs) are an important cause of
      hospitalizations and mortality among hemodialysis (HD) patients. Epidemiology of
      these infections is changing, with increasing rates of Gram-negative pathogens,
      including resistant ones. Few studies have focused on the characteristics and
      outcomes of these infections. OBJECTIVE: We aimed to document the causative
      pathogens of BSIs in HD patients and their clinical outcomes during 2008 - 2015,
      and to compare risk factors, clinical features, appropriateness of therapy, and
      outcomes between patients with Gram-negative vs. Gram-positive BSIs. MATERIALS
      AND METHODS: A single-center retrospective cohort study. Charts of 120 HD
      patients hospitalized with first BSI were reviewed. RESULTS: A total of 120
      patients were included, 61 episodes of Gram-negative (51.8%) and 59 episodes of
      Gram-positive bacteria (49.2%). Source of infection was significantly more likely
      to be urinary or abdominal among patients with Gram-negative infection.
      Otherwise, no statistically significant differences were documented between
      groups in terms of baseline characteristics, presentation of infection and
      outcomes. Most Gram-negative BSIs were caused by enterobacteriaceae, followed by
      Pseudomonas spp. Previous clinical or surveillance cultures added little to
      accurate prediction of the causative organism. CONCLUSION: In a cohort of HD
      patients with BSI, no significant differences were found between Gram-negative
      and Gram-positive BSIs, besides source of infection. A urinary or abdominal
      source strongly suggests a Gram-negative pathogen. Otherwise, patient's
      characteristics, clinical presentation, and previous cultures, all cannot
      accurately predict the causative pathogen of BSI, and broad-spectrum antibiotics
      should be used empirically.?.

PMID- 29648530
TI  - Clinical and histological features of antineutrophil cytoplasmic antibody
      associated vasculitis related to antithyroid drugs?.
AB  - BACKGROUND: Antithyroid drugs such as propylthiouracil and methimazole have been
      reported to cause antineutrophil cytoplasmic antibody (ANCA)-associated
      vasculitis (AAV), but little is known about long-term outcomes. MATERIALS AND
      METHODS: We identified AAV patients who underwent renal biopsy and
      retrospectively assessed their clinical and histological findings. Patients with
      AAV who had received propylthiouracil or methimazole were defined as having
      antithyroid drug-associated AAV (ATD-AAV), and the other patients were defined as
      having primary AAV. RESULTS: Seven patients with ATD-AAV and 83 patients with
      primary AAV were identified. Compared with the primary AAV group, the patients
      with ATD-AAV were significantly younger (mean +/- standard deviation; 45.4 +/-
      21.4 years vs. 65.9 +/- 13.8 years, p < 0.01), and had lower serum creatinine
      (median [interquartile range]; 0.7 mg/dL [0.6 - 1.5] vs. 2.3 mg/dL [1.0 - 4.0], p
      = 0.02), as well as a higher frequency of positivity for MPO--ANCA/PR3-ANCA (42.9
      vs. 4.8%, p < 0.01). While glomerular crescents varied, interstitial fibrosis and
      tubular atrophy were milder in ATD-AAV patients. Kaplan-Meier analysis showed a
      significantly higher kidney survival rate in patients with ATD-AAV than in those
      with primary AAV (p = 0.05). CONCLUSION: Patients with ATD-AAV were younger and
      had milder kidney involvement, resulting in a better long-term outcome compared
      with primary AAV.?.

PMID- 29648531
TI  - Propafenone quantification in human plasma by high-performance liquid
      chromatography coupled with electrospray tandem mass spectrometry in a
      bioequivalence study?.
AB  - Propafenone is an antiarrhythmic drug applied to ventricular arrhythmias,
      initially recognized as a sodium channel blocker. This study aims to evaluate the
      bioequivalence of two propafenone formulations (300 mg tablet) in healthy
      subjects under non-fasting conditions. The study was conducted as an open,
      randomized, 2-period design with a 2-sequence (RT, TR) with a 1-week washout
      interval. The subjects were selected for the study after having their health
      status previously assessed by a clinical evaluation and laboratory tests
      (biochemical and hematological parameters, and urinalysis). Debrisoquine
      phenotype of healthy subjects was determined by analysis of urinary excretion of
      debrisoquine and its major metabolite, 4-hydroxydebrisoquine. A single
      propafenone tablet (300 mg) was given in each occasion. Plasma propafenone
      concentrations were analyzed by liquid chromatography coupled to tandem mass
      spectrometry (HPLC/MS/MS) with positive ion electrospray ionization using
      multiple reactions monitoring (MRM). The geometric mean and 90% confidence
      intervals (CI) of propafenone/Ritmonorm<sup>(r)</sup> (T/R) percent ratio were
      100.44% (88.39 - 114.13%) for AUC<sub>last</sub>, 99.84% (90.31 - 110.36%) for
      AUC<sub>inf</sub>, and 99.30% (90.08 - 109.47%) for C<sub>max</sub>. Since the
      90% CI for C<sub>max</sub>, AUC<sub>last</sub>, and AUC<sub>inf</sub> ratios were
      all inside the 80 - 125% interval proposed by the US Food and Drug Administration
      Agency, it was concluded that the propafenone formulation elaborated by Biolab
      Sanus Farmaceutica Ltda. is bioequivalent to Ritmonorm<sup>(r)</sup> formulation
      for both the rate and the extent of absorption. The drug was well tolerated by
      the subjects, indicating that it is safe to perform propafenone bioequivalence
      studies in healthy subjects with intermediate/extensive metabolism.?.

PMID- 29648532
TI  - Bioequivalence of a fixed-dose repaglinide/metformin combination tablet and
      equivalent doses of repaglinide and metformin tablets?.
AB  - OBJECTIVE: This study was conducted to determine whether a fixed-dose combination
      (FDC) tablet of repaglinide/metformin (2/500 mg) is equivalent to
      coadministration of equivalent doses of individual (EDI) tablets of repaglinide
      (2 mg) and metformin (500 mg) in healthy Korean male subjects. MATERIALS AND
      METHODS: This study was conducted as an open-label, randomized, single-dose, two
      period, two-sequence crossover design in 50 healthy Korean male subjects who
      received an FDC tablet or EDI tablets. Plasma concentrations of repaglinide and
      metformin were determined for up to 24 hours using a validated UPLC-MS/MS method.
      Bioequivalence was assessed according to current guidelines issued by the U.S.
      Food and Drug Administration (FDA) and Korean legislation. Tolerability was also
      evaluated throughout the study via subject interview, vital signs, and blood
      sampling. RESULTS: Point estimates (90% CIs) for AUC<sub>0-t</sub>, AUC<sub>0
      infinity</sub>, and C<sub>max</sub> based on EDI tablets were 110.07 (102.25 -
      118.49), 109.90 (101.70 - 118.39), and 112.60 (101.49 - 124.85), respectively,
      for repaglinide. They were 95.18 (89.62 - 101.05), 95.00 (89.74 - 100.65), and
      98.44 (92.72 - 104.50), respectively, for metformin. These results satisfied the
      bioequivalence criteria of 80.00 - 125.00% proposed by the FDA and Korean
      legislation. CONCLUSION: Results of pharmacokinetic analysis suggested that
      repaglinide and metformin in FDC tablets were bioequivalent to EDI tablets of
      repaglinide (2 mg) and metformin (500 mg) in healthy Korean male subjects. Both
      formulations appeared to be well tolerated.?.

PMID- 29648533
TI  - Effect of fluconazole on the pharmacokinetics of everolimus and tacrolimus in a
      heart transplant recipient: Case report.
AB  - OBJECTIVE: Everolimus is an inhibitor of the mammalian target of rapamycin (mTOR)
      and has been used in combination with calcineurin inhibitors (tacrolimus and
      cyclosporine) to prevent allograft rejection following organ transplantation. In
      heart transplant recipients, everolimus should be maintained at a target blood
      concentration of 3 - 8 ng/mL, in combination with reduced-dose calcineurin
      inhibitors and therefore, requires strict monitoring. Fluconazole, an azole
      antifungal agent, affects blood concentration of tacrolimus by inhibiting the
      cytochromes P450 (CYP) 3A4 and 3A5. Therefore, to avoid overexposure during
      everolimus-azole cotreatment, the dose of everolimus should be reduced. However,
      the mechanism of interaction between everolimus and fluconazole remains unclear.
      CASE REPORT: We report the case of a heart transplant recipient who experienced a
      2.8-fold increase in everolimus clearance and a 3.5-fold increase in everolimus
      dosage, following withdrawal of fluconazole therapy. The clearance and dosage of
      tacrolimus increased 4.7- and 3.0-fold, respectively. CONCLUSION: The
      concentrations of everolimus and tacrolimus should be carefully monitored when
      administered concomitantly with fluconazole to heart transplant recipients. The
      patient in this case had a CYP3A5*1/*3 genotype, and CYP3A5 constituted the
      metabolic pathway. Therefore, concomitant use of fluconazole might have a
      relatively small impact on everolimus and tacrolimus pharmacokinetics in this
      case.?.

PMID- 29648534
TI  - Chromatin-associated RNA sequencing (ChAR-seq) maps genome-wide RNA-to-DNA
      contacts.
AB  - RNA is a critical component of chromatin in eukaryotes, both as a product of
      transcription, and as an essential constituent of ribonucleoprotein complexes
      that regulate both local and global chromatin states. Here, we present a
      proximity ligation and sequencing method called Chromatin-Associated RNA
      sequencing (ChAR-seq) that maps all RNA-to-DNA contacts across the genome. Using
      Drosophila cells, we show that ChAR-seq provides unbiased, de novo identification
      of targets of chromatin-bound RNAs including nascent transcripts, chromosome
      specific dosage compensation ncRNAs, and genome-wide trans-associated RNAs
      involved in co-transcriptional RNA processing.

PMID- 29648535
TI  - Evidence for loss and reacquisition of alcoholic fermentation in a fructophilic
      yeast lineage.
AB  - Fructophily is a rare trait that consists of the preference for fructose over
      other carbon sources. Here, we show that in a yeast lineage (the
      Wickerhamiella/Starmerella, W/S clade) comprised of fructophilic species thriving
      in the high-sugar floral niche, the acquisition of fructophily is concurrent with
      a wider remodeling of central carbon metabolism. Coupling comparative genomics
      with biochemical and genetic approaches, we gathered ample evidence for the loss
      of alcoholic fermentation in an ancestor of the W/S clade and subsequent
      reinstatement through either horizontal acquisition of homologous bacterial genes
      or modification of a pre-existing yeast gene. An enzyme required for sucrose
      assimilation was also acquired from bacteria, suggesting that the genetic
      novelties identified in the W/S clade may be related to adaptation to the high
      sugar environment. This work shows how even central carbon metabolism can be
      remodeled by a surge of HGT events.

PMID- 29648536
TI  - Silencing of transposable elements may not be a major driver of regulatory
      evolution in primate iPSCs.
AB  - Transposable elements (TEs) comprise almost half of primate genomes and their
      aberrant regulation can result in deleterious effects. In pluripotent stem cells,
      rapidly evolving KRAB-ZNF genes target TEs for silencing by H3K9me3. To
      investigate the evolution of TE silencing, we performed H3K9me3 ChIP-seq
      experiments in induced pluripotent stem cells from 10 human and 7 chimpanzee
      individuals. We identified four million orthologous TEs and found the SVA and ERV
      families to be marked most frequently by H3K9me3. We found little evidence of
      inter-species differences in TE silencing, with as many as 82% of putatively
      silenced TEs marked at similar levels in humans and chimpanzees. TEs that are
      preferentially silenced in one species are a similar age to those silenced in
      both species and are not more likely to be associated with expression divergence
      of nearby orthologous genes. Our data suggest limited species-specificity of TE
      silencing across 6 million years of primate evolution.

PMID- 29648537
TI  - The conformation of the histone H3 tail inhibits association of the BPTF PHD
      finger with the nucleosome.
AB  - Histone tails harbor a plethora of post-translational modifications that direct
      the function of chromatin regulators, which recognize them through effector
      domains. Effector domain/histone interactions have been broadly studied, but
      largely using peptide fragments of histone tails. Here, we extend these studies
      into the nucleosome context and find that the conformation adopted by the histone
      H3 tails is inhibitory to BPTF PHD finger binding. Using NMR spectroscopy and MD
      simulations, we show that the H3 tails interact robustly but dynamically with
      nucleosomal DNA, substantially reducing PHD finger association. Altering the
      electrostatics of the H3 tail via modification or mutation increases
      accessibility to the PHD finger, indicating that PTM crosstalk can regulate
      effector domain binding by altering nucleosome conformation. Together, our
      results demonstrate that the nucleosome context has a dramatic impact on
      signaling events at the histone tails, and highlights the importance of studying
      histone binding in the context of the nucleosome.

PMID- 29648538
TI  - Wnt5a signaling induced phosphorylation increases APT1 activity and promotes
      melanoma metastatic behavior.
AB  - Wnt5a has been implicated in melanoma progression and metastasis, although the
      exact downstream signaling events that contribute to melanoma metastasis are
      poorly understood. Wnt5a signaling results in acyl protein thioesterase 1 (APT1)
      mediated depalmitoylation of pro-metastatic cell adhesion molecules CD44 and
      MCAM, resulting in increased melanoma invasion. The mechanistic details that
      underlie Wnt5a-mediated regulation of APT1 activity and cellular function remain
      unknown. Here, we show Wnt5a signaling regulates APT1 activity through induction
      of APT1 phosphorylation and we further investigate the functional role of APT1
      phosphorylation on its depalmitoylating activity. We found phosphorylation
      increased APT1 depalmitoylating activity and reduced APT1 dimerization. We
      further determined APT1 phosphorylation increases melanoma invasion in vitro, and
      also correlated with increased tumor grade and metastasis. Our results further
      establish APT1 as an important regulator of melanoma invasion and metastatic
      behavior. Inhibition of APT1 may represent a novel way to treat Wnt5a driven
      cancers.

PMID- 29648539
TI  - Horizontal Gene Transfer in Thermus spp.
AB  - The small amount of genetic content in thermophiles generally limits their
      adaptability to environmental changes. In Thermus spp., very active horizontal
      gene transfer (HGT) mechanisms allow the rapid spread of strain-specific adaptive
      gene modules among the entire population. Constitutive expression of a rather
      particular and highly efficient DNA transport apparatus (DTA) is at the center of
      this HGT-mediated enhanced adaptability. The function of the DTA is dependent on
      the integrity and longevity of the extracellular DNA (eDNA) being transformed,
      which can be improved by the production of extracellular vesicles (EV) through
      lysis of a fraction of the population. The DTA must also contend with the
      recipient cell's defensive barriers, namely restriction enzymes, a panoply of
      CRISPR-Cas systems, and the argonaute-like protein TtAgo, which may be bypassed
      by transjugation, a new class of bidirectional transformation-dependent
      conjugation. Efficient transjugation depends on the presence of the ICETh1, an
      integrative and conjugative element which promotes simultaneous, generalized DNA
      transfer from several points in the genome. Transjugation shows preference for
      genes located within a megaplasmid replicon, where the main strain-specific
      adaptive modules are located. Contribution of transformation, vesicle-mediated
      eDNAs, and transjugation to HGT in this genus is discussed.

PMID- 29648540
TI  - Editorial: ICE and Small.
AB  - Bacterial genomes vary considerably in terms of size and gene content. The
      proportion of a genome composed of horizontally acquired DNA or mobile genetic
      elements also varies, but follows an ecological pattern with more mobile genetic
      element genes being found in facultative intracellular bacteria than those
      considered extracellular and both containing more than obligately intracellular
      bacteria.

PMID- 29648541
TI  - Horizontal Gene Transfers in Mycoplasmas (Mollicutes).
AB  - The class Mollicutes (trivial name "mycoplasma") is composed of wall-less
      bacteria with reduced genomes whose evolution was long thought to be only driven
      by gene losses. Recent evidences of massive horizontal gene transfer (HGT) within
      and across species provided a new frame to understand the successful adaptation
      of these minimal bacteria to a broad range of hosts. Mobile genetic elements are
      being identified in a growing number of mycoplasma species, but integrative and
      conjugative elements (ICEs) are emerging as pivotal in HGT. While sharing common
      traits with other bacterial ICEs, such as their chromosomal integration and the
      use of a type IV secretion system to mediate horizontal dissemination, mycoplasma
      ICEs (MICEs) revealed unique features: their chromosomal integration is totally
      random and driven by a DDE recombinase related to the Mutator-like superfamily.
      Mycoplasma conjugation is not restricted to ICE transmission, but also involves
      the transfer of large chromosomal fragments that generates progenies with mosaic
      genomes, nearly every position of chromosome being mobile. Mycoplasmas have thus
      developed efficient ways to gain access to a considerable reservoir of genetic
      resources distributed among a vast number of species expanding the concept of
      minimal cell to the broader context of flowing information.

PMID- 29648542
TI  - The indispensable role of the transversal spin fluctuations mechanism in laser
      induced demagnetization of Co/Pt multilayers with nanoscale magnetic domains.
AB  - The switching of magnetic domains induced by an ultrashort laser pulse has been
      demonstrated in nanostructured ferromagnetic films. This leads to the dawn of a
      new era in breaking the ultimate physical limit for the speed of magnetic
      switching and manipulation, which is relevant to current and future information
      storage. However, our understanding of the interactions between light and spins
      in magnetic heterostructures with nanoscale domain structures is still lacking.
      Here, both time-resolved magneto-optical Kerr effect experiments and atomistic
      simulations are carried out to investigate the dominant mechanism of laser
      induced ultrafast demagnetization in [Co/Pt]20 multilayers with nanoscale
      magnetic domains. It is found that the ultrafast demagnetization time remains
      constant with various magnetic configurations, indicating that the domain
      structures play a minor role in laser-induced ultrafast demagnetization. In
      addition, both in experiment and atomistic simulations, we find a dependence of
      ultrafast demagnetization time tau M on the laser fluence, which is in contrast
      to the observations of spin transport within magnetic domains. The remarkable
      agreement between experiment and atomistic simulations indicates that the local
      dissipation of spin angular momentum is the dominant demagnetization mechanism in
      this system. More interestingly, we made a comparison between the atomistic spin
      dynamic simulation and the longitudinal spin flip model, highlighting that the
      transversal spin fluctuations mechanism is responsible for the ultrafast
      demagnetization in the case of inhomogeneous magnetic structures. This is a
      significant advance in clarifying the microscopic mechanism underlying the
      process of ultrafast demagnetization in inhomogeneous magnetic structures.

PMID- 29648543
TI  - Modeling and predictions of biphasic mechanosensitive cell migration altered by
      cell-intrinsic properties and matrix confinement.
AB  - Motile cells sense the stiffness of their extracellular matrix through adhesions
      and respond by modulating the generated forces, which in turn lead to varying
      mechanosensitive migration phenotypes. Through modeling and experiments, cell
      migration speed is known to vary with matrix stiffness in a biphasic manner, with
      optimal motility at an intermediate stiffness. Here, we present a 2D cell model
      defined by nodes and elements, integrated with subcellular modeling components
      corresponding to mechanotransductive adhesion formation, force generation,
      protrusions and node displacement. On 2D matrices, our calculations reproduce the
      classic biphasic dependence of migration speed on matrix stiffness and predict
      that cell types with higher force-generating ability do not slow down on very
      stiff matrices, thus disabling the biphasic response. We also predict that cell
      types defined by a lower number of total receptors require stiffer matrices for
      optimal motility, which also limits the biphasic response. For a cell type with
      robust biphasic migration on a 2D surface, simulations in channel-like confined
      environments of varying width and height predict faster migration in more
      confined matrices. Simulations performed in shallower channels predict that the
      biphasic mechanosensitive cell migration response is more robust on 2D micro
      patterns compared to the channel-like 3D confinement. Thus, variations in the
      dimensionality of matrix confinement alters the way migratory cells sense and
      respond to the matrix stiffness. Our calculations reveal new phenotypes of
      stiffness- and topography-sensitive cell migration that critically depend on both
      cell-intrinsic and matrix properties. These predictions may inform our
      understanding of various mechanosensitive modes of cell motility that could
      enable tumor invasion through topographically heterogeneous microenvironments.

PMID- 29648544
TI  - SiGe nano-heteroepitaxy on Si and SiGe nano-pillars.
AB  - In this paper, SiGe nano-heteroepitaxy on Si and SiGe nano-pillars was
      investigated in a 300 mm industrial reduced pressure-chemical vapour deposition
      tool. An integration scheme based on diblock copolymer patterning was used to
      fabricate nanometre-sized templates for the epitaxy of Si and SiGe nano-pillars.
      Results showed highly selective and uniform processes for the epitaxial growth of
      Si and SiGe nano-pillars. 200 nm thick SiGe layers were grown on Si and SiGe nano
      pillars and characterised by atomic force microscopy, x-ray diffraction and
      transmission electron microscopy. Smooth SiGe surfaces and full strain relaxation
      were obtained in the 650  degrees C-700  degrees C range for 2D SiGe layers grown
      either on Si or SiGe nano-pillars.

PMID- 29648545
TI  - Enhancement of aerodynamic performance of a heaving airfoil using synthetic-jet
      based active flow control.
AB  - In this study, we explore the use of synthetic jet (SJ) in manipulating the
      vortices around a rigid heaving airfoil, so as to enhance its aerodynamic
      performance. The airfoil heaves at two fixed pitching angles, with the Strouhal
      number, reduced frequency and Reynolds number chosen as St  =  0.3, k  =  0.25
      and Re  =  100, respectively, all falling in the ranges for natural flyers. As
      such, the vortex force plays a dominant role in determining the airfoil's
      aerodynamic performance. A pair of in-phase SJs is implemented on the airfoil's
      upper and lower surfaces, operating with the same strength but in opposite
      directions. Such a fluid-structure interaction problem is numerically solved
      using a lattice Boltzmann method based numerical framework. It is found that, as
      the airfoil heaves with zero pitching angle, its lift and drag can be improved
      concurrently when the SJ phase angle [Formula: see text] relative to the heave
      motion varies between [Formula: see text] and [Formula: see text]. But this
      concurrent improvement does not occur as the airfoil heaves with [Formula: see
      text] pitching angle. Detailed inspection of the vortex evolution and fluid
      stress over the airfoil surface reveals that, if at good timing, the suction and
      blowing strokes of the SJ pair can effectively delay or promote the shedding of
      leading edge vortices, and mitigate or even eliminate the generation of trailing
      edge vortices, so as to enhance the airfoil's aerodynamic performance. Based on
      these understandings, an intermittent operation of the SJ pair is then proposed
      to realize concurrent lift and drag improvement for the heaving airfoil with
      [Formula: see text] pitching angle.

PMID- 29648546
TI  - Photoreduction of carbon dioxide under visible light by ultra-small Ag
      nanoparticles doped into Co-ZIF-9.
AB  - Metal-organic frameworks (MOFs) are well-known porous materials able to adsorb
      CO2, and their performance in CO2 reduction has attracted much attention from
      researchers. A classical Co-MOF, Co-ZIF-9, has been proposed as a novel
      photocatalyst for reducing CO2 into chemical feedstocks. Herein, Co-ZIF-9 with a
      rod-like structure was obtained through reflux. Ultra-small silver nanoparticles
      (Ag NPs, smaller than 5 nm) were doped into Co-ZIF-9 by the photodeposition
      method. With the assistance of a photosensitizer, the resultant composite Ag@Co
      ZIF-9 shows catalytic reactivity in converting CO2 into CO under visible light
      irradiation. Compared with bare Co-ZIF-9, the photocatalytic performance of Ag@Co
      ZIF-9 increases by more than twofold (around 28.4 MUmol CO) and the selectivity
      is enhanced by about 20% (22.9 MUmol H2) for 0.5 h of irradiation. This
      demonstrates that Ag NPs doping may provide a possible way to promote the
      efficiency and selectivity of MOF materials in CO2 photoreduction.

PMID- 29648547
TI  - Controllable synthesizing DLC nano structures as a super hydrophobic layer on
      cotton fabric using a low-cost ethanol electrospray-assisted atmospheric plasma
      jet.
AB  - The surface modification of cotton samples was carried out using a liquid
      (ethanol) electrospray-assisted atmospheric pressure plasma jet. X-ray
      photoelectron spectroscopy (XPS) and Raman analysis confirmed the successful
      deposition of diamond like carbon (DLC) nano structures on the cotton surface.
      The super hydrophobic state of the samples was probed by contact angle
      measurements. The water repellency of the layers was tuned by controlling the
      voltage applied to the electrospray electrode. An investigation of the
      morphological and chemical structures of the samples by field emission scanning
      microscopy, atomic force microscopy (AFM) and XPS indicated that the physical
      shape, distribution and amorphization of the DLC structures were successfully
      adjusted and improved by applying a voltage to the electrospray electrode.
      Finally wash durability of the best sample was tested for 35 cycles. In this
      work, the use of a well-developed atmospheric pressure plasma jet for DLC nano
      structures deposition can enable a promising environmentally friendly and low
      cost approach for modifying cotton fabrics for super water-repellent fabric
      applications.

PMID- 29648548
TI  - Dimensional quantization effects in the thermodynamics of conductive filaments.
AB  - We consider the physical effects of dimensional quantization in conductive
      filaments that underlie operations of some modern electronic devices. We show
      that, as a result of quantization, a sufficiently thin filament acquires a
      positive charge. Several applications of this finding include the host material
      polarization, the stability of filament constrictions, the equilibrium filament
      radius, polarity in device switching, and quantization of conductance.

PMID- 29648549
TI  - Morphology effect on photocatalytic activity in Bi3Fe0.5Nb1.5O9.
AB  - In this work, the Aurivillius-phase ferroelectric Bi3Fe0.5Nb1.5O9 were
      synthesized by hydrothermal (BFNO-H) and solid state methods (BFNO-S),
      respectively. The BFNO-H shows a hierarchical morphology, which is stacked by
      intersecting single-crystal nanosheets with {001} and {110} exposed facets, while
      the BFNO-S shows disorganized micron-scale morphology. BFNO-H shows a much
      stronger photodegradation activity (10.4 times and 9.8 times) than BFNO-S in the
      visible-light photodegradation of rhodamine B (RhB) and salicylic acid. The
      higher photodegradation activity of BFNO-H was firstly ascribed to the
      hierarchical structure and the larger specific surface area (16.586 m2 g-1)
      because a large specific surface area can increase reactive sites and shorten
      photogenerated carrier migration distance. However, after being normalized by the
      specific surface area, BFNO-H still performs better than BFNO-S, implying that
      the specific surface area is not the only factor that determines the
      photocatalytic activity. Considering that the built-in electric field originating
      from spontaneous polarization in Bi3Fe0.5Nb1.5O9 has existed in both ab plane and
      c direction, it matches well with the {001} and {110} exposed facets of BFNO-H
      nanosheets. This appropriate matching in BFNO-H nanosheets may improve the
      separation and transmission of photogenerated electron-hole pairs and further
      enhance its photocatalytic activity. Moreover, the trapping experiments reveals
      that holes (h +) are the main active species and hole-derived oxidation is the
      main redox reaction during photodegradation of organic pollutions.

PMID- 29648550
TI  - Continuous real-time breath analysis in ruminants: effect of eructation on
      exhaled VOC profiles.
AB  - BACKGROUND: The analysis of volatile organic compounds (VOCs) in breath allows
      non-invasive investigations of diseases. Animal studies are conducted as a model
      to perform research of VOCs and their relation to diseases. In large animal
      models ruminants were often used as experimental targets. The effect of their
      physiological eructation on VOC exhalation has not been examined yet and is the
      objective of this study. METHODS: Continuous breath profiles of two young cattle,
      four adult goats and four adult sheep were measured through a mask, covering
      mouth and nose, in real-time (200 ms) by means of proton transfer reaction time
      of flight mass spectrometry. Each animal was analysed twelve times for 3
      consecutive minutes. RESULTS: Real-time monitoring yielded a distinction of
      different episodes in the breath profiles of ruminants. An algorithm to separate
      eructation episodes and alveolar breath was established. In the first exhalation
      after eructation at least 19 VOC concentrations increased (up to 36-fold) and
      went back to initial levels in subsequent exhalations in all investigated
      ruminants. Decay of concentrations was substance specific. In goats, less VOCs
      were affected by the eructation compared to cattle and sheep. Breath profiles
      without exclusion of eructation episodes showed higher variations and median
      values than profiles where eructation episodes were excluded. CONCLUSION: Real
      time breath analysis of ruminants enables the discrimination and characterisation
      of alveolar breath and eructation episodes. This leads to a better understanding
      of variation in breath data and possible origins of VOCs: breath or digestion
      related. To avoid impairment of breath gas results and to gain further
      information on bacterial products from the rumen, eructation and alveolar breath
      data should be analysed separately.

PMID- 29648551
TI  - Size-dependent single electron transfer and semi-metal-to-insulator transitions
      in molecular metal oxide electronics.
AB  - All-inorganic self-arranged molecular transition metal oxide hyperstructures
      based on polyoxometalate molecules (POMs) are fabricated and tested as
      electronically tunable components in emerging electronic devices. POM
      hyperstructures reveal great potential as charging nodes of tunable charging
      level for molecular memories and as enhancers of interfacial electron/hole
      injection for photovoltaic stacks. STM, UPS, UV-vis spectroscopy and AFM
      measurements show that this functionality stems from the films' ability to
      structurally tune their HOMO-LUMO levels and electron localization length at room
      temperature. By adapting POM nanocluster size in solution, self-doping and
      current modulation of four orders of magnitude is monitored on a single
      nanocluster on SiO2 at voltages as low as 3 Volt. Structurally driven insulator
      to-semi-metal transitions and size-dependent current regulation through single
      electron tunneling are demonstrated and examined with respect to the
      stereochemical and electronic structure of the molecular entities. This extends
      the value of self-assembly as a tool for correlation length and electronic
      properties tuning and demonstrate POM hyperstructures' plausibility for on-chip
      molecular electronics operative at room temperature.

PMID- 29648552
TI  - Role of Ni2+(d8) ions in electrical, optical and magnetic properties of CdS
      nanowires for optoelectronic and spintronic applications.
AB  - For the first time, 1D Ni ion doped CdS nanowires (NWs) were synthesized via
      chemical vapour deposition (CVD). The synthesized Cd0.886Ni0.114S NWs were single
      crystalline. We have reported here the investigation of optical, electrical and
      magnetic properties of prepared NWs for optoelectronic and spintronic
      applications. Successful incorporation of Ni ions in an individual CdS NW has
      been confirmed through several characterization tools: significantly higher angle
      and phonon mode shift were observed in the XRD and Raman spectra. SEM-EDX and XPS
      analysis also confirmed the presence of Ni2+ ions. Room temperature
      photoluminescence (RT-PL) showed multiple peaks: two emission peaks in the
      visible region centered at 517.1 nm (green), 579.2 nm (orange), and a broad-band
      near infra-red (NIR) emission centered at 759.9 nm. The first peak showed 5 nm
      red shift upon Ni2+ doping, hinting at the formation of exciton magnetic polarons
      (EMPs), and broad NIR emission was observed in both chlorides and bromides, which
      was assigned to d-d transition of Ni ions whose energy levels lying at 749.51 nm
      (13 342 cm-1) and 750.98 nm (13 316 cm-1) are very close to NIR emission. Orange
      emission not only remained at same peak position-its PL intensity was also
      significantly enhanced at 78 K; this was assigned to d-d transition (3A2g -> 1Eg)
      of Ni2+ ions. It was observed that 11.4% Ni2+ ion doping enhanced the
      conductivity of our sample around 20 times, and saturation magnetization (Ms)
      increased from 7.2 * 10-5 Am2/Kg to 1.17 * 10-4 Am2/Kg, which shows promise for
      optoelectronic and spintronic applications.

PMID- 29648554
TI  - Discovery of quinazoline-2,4(1H,3H)-dione derivatives as novel PARP-1/2
      inhibitors: design, synthesis and their antitumor activity.
AB  - Novel quinazoline-2,4(1H,3H)-dione derivatives bearing a 3-amino pyrrolidine
      moiety were designed and synthesized as PARP-1/2 inhibitors. Structure-activity
      relationships were examined which revealed a number of potent PARP-1/2 inhibitors
      with moderate selectivity toward PARP-1 over PARP-2. These compounds had IC50
      values against PARP-1 at the 10-9 M level and against PARP-2 at the 10-8 M level.
      Among all the synthesized compounds, compounds 10 and 11 displayed strong
      cytotoxicities which are either used as a single agent or in combination with
      temozolomide (TMZ) in MX-1 cells (10, IC50 < 3.12 MUM, PF50 > 10; 11, IC50 = 3.02
      MUM, PF50 ~ 10). In vivo tumor growth inhibition was investigated using compound
      11 in combination with TMZ, and it was demonstrated that compound 11 could
      strongly potentiate the cytotoxicity of TMZ in a MX-1 xenograft tumor model. The
      co-crystal structure of compound 11 complexed with PARP-1 was achieved and
      demonstrated a unique binding mode.

PMID- 29648553
TI  - Health-related quality of life in bladder cancer patients undergoing radical
      cystectomy and urinary stoma: still many gaps.

PMID- 29648555
TI  - Thermal conductivity of ice polymorphs: a computational study.
AB  - Thermal transport in ice features an unusual response. In addition to its
      intrinsic scientific interest, an understanding of the mechanisms determining the
      thermal conductivity of ice might be relevant in climate modelling and planetary
      science. Accurate microscopic models can provide important molecular insight into
      these mechanisms. In this work, we quantify using molecular simulations and state
      of the art forcefields, the thermal conductivity of ice Ih, VI, VII and a plastic
      phase that has been proposed very recently at pressures in the GPa range. The
      TIP4P models used in this study underestimate significantly the thermal
      conductivity of ice Ih and ice VII, while they show good agreement with
      experimental measurements of ice VI. The discrepancies observed are examined by
      investigating the temperature dependence of the thermal conductivity. The
      simulations indicate that the models are too anharmonic and they potentially
      feature a higher structural disorder than the experimental systems. We suggest
      that at high pressures the simulated thermal conductivities can be rationalized
      in terms of the performance of the models in predicting the equation of state of
      ice. The thermal conductivity of the plastic phase is very similar to that of the
      coexisting ice VII. Since the water molecules in the plastic phase feature
      orientational disorder, these results indicate that the hydrogen bond network
      does not play a significant role in defining the thermal transport mechanisms of
      ice at high pressures.

PMID- 29648556
TI  - Selective formation of formamidines, carbodiimides and formimidates from
      isocyanide complexes of Mn(i) mediated by Ag2O.
AB  - The isocyanide ligands in complexes fac-[Mn(CNR)(bipy)(CO)3]+ are selectively
      transformed into formamidines, carbodiimides and formimidates upon nucleophilic
      addition of NH2Me or alkoxides and subsequent treatment with Ag2O, which promotes
      tautomerization or oxidation processes of the former carbene ligands.

PMID- 29648557
TI  - Ligand-mediated synthesis of compositionally related cesium lead halide CsPb2X5
      nanowires with improved stability.
AB  - Compositionally related cesium lead halide materials, such as CsPb2X5, have
      attracted great interest due to their considerable optoelectronic/optical
      properties as well as improved stability. Currently, CsPb2Br5 nanocrystals can be
      well-designed by tuning the ligands or precursor ratio, whereas, CsPb2X5 (with Cl
      or I-) nanocrystals can only be obtained by the anion exchange method. Herein,
      we report a method to directly synthesize CsPb2X5 facilitated by thiol ligands.
      The morphology of CsPb2X5 can be designed as a nanowire. Importantly, the
      stability of directly synthesized CsPb2X5 nanowires is much improved when
      compared with the stabilities of the materials obtained by the anion-exchange
      method. We believe that this method will promote the application of 1D tetragonal
      CsPb2X5 in optoelectronics, optics and other fields.

PMID- 29648558
TI  - Photo-induced anticancer activity and singlet oxygen production of prodigiosenes.
AB  - The photo-induced cytotoxicity of prodigiosenes is reported. One prodigiosene
      represents a synthetic analogue of the natural product prodigiosin, and two are
      conjugated to molecules that target the estrogen receptor (ER). A comparison of
      incubation and irradiation frameworks for the three prodigiosenes is reported,
      with activity against ER- and ER+ lines explored. Furthermore, the ability of the
      three prodigiosenes to photosensitise the production of singlet oxygen is
      demonstrated, shedding mechanistic light onto possible photodynamic therapeutic
      effects of this class of tripyrroles.

PMID- 29648560
TI  - Multifunctional hybrids with versatile types of nanoparticles via self-assembly
      for complementary tumor therapy.
AB  - Self-assembly is a promising method for the construction of multifunctional
      nanohybrids for biomedical application. In this work, self-assembled
      multifunctional nanohybrids with a controllable disassembly property have been
      successfully fabricated. By modification with cyclodextrin (CD)-decorated
      ethylenediamine-functionalized poly(glycidyl methacrylate) (PGED), CD groups and
      polycations were conjugated onto Au nanorods (Au NRs) or Fe3O4 nanoparticles
      (denoted as Au-PGED-CD or Fe3O4-PGED-CD), and different SiO2@Fe3O4-PGED (SFP) or
      SiO2@Au-PGED (SAP) nanohybrids were readily fabricated by the host-guest
      interaction between Au-PGED-CD or Fe3O4-PGED-CD and adamantyl (Ad)-functionalized
      chiral silica NRs under mild conditions. The DNA condensation ability of the
      polycation, the photothermal effects of Au NRs or Fe3O4 nanoparticles, as well as
      the unique structure of chiral silica NRs were integrated into one nanohybrid.
      Such nanohybrids have high gene transfection efficiency and low cytotoxicity. The
      photothermal effects of the nanohybrids could be utilized for photothermal
      therapy, and also could induce the disassembly of the nanohybrids, which is
      beneficial for DNA release. The nanohybrids with good transfection performance
      and excellent photothermal effects were further applied for multimodal therapy.
      This work presents a flexible strategy for the fabrication of multifunctional
      nanoplatforms with integration of the advantages of various types of
      nanoparticles.

PMID- 29648559
TI  - Significant effects of counteranions on the anticancer activity of iridium(iii)
      complexes.
AB  - The rational design of the ligands around transition metals has achieved success
      in the development of anticancer complexes. In this contribution, a series of
      organometallic half-sandwich iridium(iii) complexes with various corresponding
      counteranions have been prepared and characterized. The size and coordination
      ability of the counteranions exert a great influence on the chemical reactivity
      and anticancer activity of these complexes. The influence of the counteranions on
      the cell cycle, apoptosis, ROS and mitochondrial membrane potential is also
      discussed. This work has shown for the first time that the modification of
      counteranions can affect the anticancer activity of transition metal-based
      complexes.

PMID- 29648561
TI  - Highlights from the Faraday discussion on photoinduced processes in nucleic acids
      and proteins.

PMID- 29648562
TI  - Synthesis and crystal structure of solvent-free dodecahydro closo-dodecaborate of
      nickel, NiB12H12.
AB  - Nickel closo-dodecaborate NiB12H12 was prepared by mechanosynthesis (ball
      milling) of mixtures of Na2B12H12 + NiCl2 followed by hydration and drying under
      dynamic vacuum. The crystal structures of hydrated and anhydrous closo
      dodecaborates were characterized by temperature dependent synchrotron radiation X
      ray powder diffraction, ab initio calculations, thermal analysis and infrared
      spectroscopy. Three different water containing complexes were found: a homoleptic
      octahedral complex in Ni(H2O)6B12H12 crystallizing in two different deformation
      variants of a complex centred closo-dodecaborate cube, and a heteroleptic
      octahedral complex in Ni(H2O)4B12H12 containing four water molecules and two
      hydrogens and centring also a deformed closo-dodecaborate cube. Anhydrous nickel
      closo-dodecaborate was obtained by drying the hydrated sample under dynamic
      vacuum. It crystallizes with bcc packing of B12H122- anions and Ni2+ is
      disordered close to the triangular face of the tetrahedral interstice coordinated
      by a H5 square pyramid.

PMID- 29648563
TI  - Trisubstituted olefin synthesis via Ni-catalyzed hydroalkylation of internal
      alkynes with non-activated alkyl halides.
AB  - The stereoselective synthesis of tri-substituted alkenes is challenging. Herein,
      we report a Ni-catalyzed regio- and stereo-selective hydroalkylation of internal
      alkynes with non-activated alkyl halides. This method does not use any sensitive
      organometallic reagents and shows good functional group compatibility, which
      enables the efficient synthesis of many tri-substituted olefins from readily
      available coupling partners. It also provides a straightforward method for the
      modification of bioactive organic molecules.

PMID- 29648564
TI  - Site-selective reversible Diels-Alder reaction between a biphenylene-based
      polyarene and a semiconductor surface.
AB  - Understanding the mechanisms involved in the covalent attachment of organic
      molecules to surfaces is a major challenge for nanotechnology and surface
      science. On the basis of classical organic chemistry mechanistic considerations,
      key issues such as selectivity and reactivity of the organic adsorbates could be
      rationalized and exploited for the design of molecular-scale circuits and
      devices. Here we use tris(benzocyclobutadieno)triphenylene, a singular Y-shaped
      hydrocarbon containing antiaromatic cyclobutadienoid rings, as a molecular probe
      to study the reaction of polycyclic conjugated molecules with atomic scale
      moieties, dangling-bond (DB) dimers on a hydrogen-passivated Ge(001):H surface.
      By combining molecular design, synthesis, scanning tunneling microscopy and
      spectroscopy (STM/STS) and computational modeling, we show that the attachment
      involves a concerted [4+2] cycloaddition reaction that is completely site
      selective and fully reversible. This selectivity, governed by the bond
      alternation induced by the presence of the cyclobutadienoid rings, allows for the
      control of the orientation of the molecules with respect to the surface DB
      patterning. We also demonstrate that by judicious modification of the electronic
      levels of the polycyclic benzenoid through substituents, the reaction barrier
      height can be modified. Finally, we show that after deliberate tip-induced
      covalent bond cleavage, adsorbed molecules can be used to fine tune the
      electronic states of the DB dimer. This power to engineer deliberately the
      bonding configuration and electronic properties opens new perspectives for
      creating prototypical nanoscale circuitry.

PMID- 29648565
TI  - The influence of pseudohalide ligands on the SIM behaviour of four-coordinate
      benzylimidazole-containing cobalt(ii) complexes.
AB  - Three, mononuclear complexes of the formula [Co(bmim)2(SCN)2] (1),
      [Co(bmim)2(NCO)2] (2) and [Co(bmim)2(N3)2] (3) [bmim = 1-benzyl-2
      methylimidazole] were prepared and structurally analyzed by single-crystal X-ray
      crystallography. The cobalt(ii) ions in 1-3 are tetrahedrally coordinated with
      two bmim molecules and two pseudohalide anions. The angular distortion parameter
      delta was calculated and the SHAPE program (based on the CShM concept) was used
      for 1-3 to estimate the angular distortion from an ideal tetrahedron. The
      molecules of 1-3 are effectively separated, and the values of the shortest
      distance of cobalt-cobalt are 8.442(6) and 6.774(8) A for 1, 10.349(8) and
      10.716(8) A for 2 and 6.778(1) and 9.232(1) A for 3. Direct current (dc) magnetic
      susceptibility measurements on the crushed crystals of 1-3 were carried out in
      the temperature range 1.9-295 K. The variable-temperature magnetic data of 1-3
      mainly obey the zero-field splitting effect (D) of the 4A2 ground term of the
      tetrahedral cobalt(ii) complexes (2D being the energy gap between the |+/-1/2 and
      |+/-3/2 levels of the spin). The analysis of their magnetic data through the
      Hamiltonian H = D[S2z - S(S + 1)/3] + E(Sx2 - Sy2) + gbetaHS led to the following
      best-fit parameters: g = 2.29, D = -7.5 cm-1 and E/D = 0.106 (1), g = 2.28, D = +
      6.3 cm-1 and E/D = 0.007 (2) and g = 2.36, D = + 6.7 cm-1 and E/D = 0.090 (3).
      The signs of D for 1-3 were confirmed by Q-band EPR spectra on powdered samples
      in the temperature range 4.0-20 K. Field-induced SIM behaviour was observed for 1
      3 below 4.0 K, and the frequency-dependent maxima of chi''M were observed for 1
      and only incipient signals of chi''M occurred for 2 and 3. The values of the
      exponential factor (tau0) and activation energy (Ea) for 1-3 which were obtained
      from the Arrhenius plot suggest a single relaxation process characteristic of an
      Orbach mechanism.

PMID- 29648566
TI  - SERS-based lateral flow assay for quantitative detection of C-reactive protein as
      an early bio-indicator of a radiation-induced inflammatory response in nonhuman
      primates.
AB  - In accidental irradiation situations, rapid in-field evaluation of acute
      radiation syndrome is critical for effective triage and timely medical treatment
      of irradiated individuals. A surface-enhanced Raman scattering (SERS)-based
      lateral flow assay was developed for the quantitative detection of C-reactive
      protein (CRP) as an early bio-indicator of a radiation-induced inflammatory
      response in nonhuman primates. Raman reporter-embedded gold-core silver-shell
      nanoparticles with built-in hot spots were synthesized and conjugated with a CRP
      detection antibody to serve as SERS tags in the lateral flow assay. The proposed
      SERS-based lateral flow assay can rapidly detect CRP with a limit of detection of
      0.01 ng mL-1 and quantitative analysis ability. Furthermore, the assay was
      applied to evaluate the CRP levels in plasma samples of irradiated nonhuman
      primates at 0 to 80 h after exposure to sublethal (4 Gy) and lethal (8 Gy) doses
      of total body irradiation (n = 3 animals per group). The plasma CRP levels
      increase rapidly within few hours after irradiation. The CRP level peaks are
      observed at 12 or 24 h after irradiation, with a concentration of 201.30, 386.06
      and 475.18 MUg mL-1 for the 4 Gy irradiated animals and 197.14, 69.52 and 358.03
      MUg mL-1 for the 8 Gy irradiated animals. The results indicate the potential
      application of the proposed SERS-based lateral flow assay to serve as a rapid and
      accurate point-of-care biodosimetry assay for the quantitative detection of bio
      indicators to triage irradiated individuals in the field of a radiation accident.

PMID- 29648567
TI  - Salt-Sensitivity of Blood Pressure: Is It Time to Customize the Antihypertensive
      Therapy?

PMID- 29648568
TI  - A Novel High-Resolution Magnetic Resonance Imaging Protocol Detects Aldosterone
      Producing Adenomas in Patients With Negative Computed Tomography.

PMID- 29648569
TI  - The Childhood Role in Development of Primary Hypertension.
AB  - Primary hypertension is not just an adult disorder. Current US population data on
      children and adolescents demonstrate a prevalence of elevated blood pressure (BP)
      and hypertension combined of over 10%. Recent reports from prospective cohort
      studies describe an association of high BP in childhood with hypertension in
      young adulthood. Excess adiposity is strongly associated with higher BP in
      childhood and increases risk for hypertension in adulthood. In addition to
      overweight/obesity, other exposures that raise the risk for high BP include low
      birthweight, dietary sodium, and stress. Using intermediate markers of
      cardiovascular injury, studies on hypertensive children report findings of
      cardiac hypertrophy, vascular stiffness, and early atherosclerotic changes.
      Impaired cognitive function has also been demonstrated in hypertensive children.
      Recent advances in clinical and translational research support the concept that
      the evolution of primary hypertension begins in childhood.

PMID- 29648570
TI  - RET-fusions: a novel paradigm in colorectal cancer.

PMID- 29648571
TI  - Engaging Fathers to Increase Physical Activity in Girls: The "Dads And Daughters
      Exercising and Empowered" (DADEE) Randomized Controlled Trial.
AB  - Background: Existing strategies to increase girls' physical activity levels have
      seen limited success. Fathers may influence their children's physical activity,
      but often spend more time with their sons and rarely participate in family-based
      programs. Purpose: To test a novel program designed to increase the physical
      activity levels of fathers and their daughters. Methods: In a two-arm RCT, 115
      fathers (29-53 years) and 153 daughters (4-12 years) were randomized to (i) the
      "Dads And Daughters Exercising and Empowered" (DADEE) program, or (ii) a wait
      list control. The 8-week program included weekly educational and practical
      sessions plus home tasks. Assessments were at baseline, 2 months
      (postintervention), and 9 months. The primary outcomes were father-daughter
      physical activity levels (pedometry). Secondary outcomes included screen-time,
      daughters' fundamental movement skill proficiency (FMS: perceived and objective),
      and fathers' physical activity parenting practices. Results: Primary outcome data
      were obtained from 88% of daughters and 90% of fathers at 9 months. Intention-to
      treat analyses revealed favorable group-by-time effects for physical activity in
      daughters (p = .02, d = 0.4) and fathers (p < .001, d = 0.7) at postintervention,
      which were maintained at 9 months. At postintervention and follow-up, significant
      effects (p < .05) were also identified for daughters' FMS competence (objective:
      d = 1.1-1.2; perceived: d = 0.4-0.6), a range of fathers' physical activity
      parenting practices (d = 0.3-0.8), and screen-time for daughters (d = 0.5-0.8)
      and fathers (d = 0.4-0.6, postintervention only). Program satisfaction and
      attendance were very high. Conclusions: This study provided the first
      experimental evidence that efforts to increase physical activity behavior in
      preadolescent girls would benefit from a meaningful engagement of fathers.
      Clinical Trial information: Australian New Zealand Clinical Trials Registry:
      ACTRN12615000022561.

PMID- 29648572
TI  - When is crossover desirable in cancer drug trials and when is it problematic?

PMID- 29648573
TI  - A comprehensive web tool for toehold switch design.
AB  - Motivation: Toehold switches are a class of RNAs with a hairpin loop that can be
      unfolded upon binding a trigger RNA, thereby exposing a ribosome binding site
      (RBS) and permitting translation of the reporter protein. They have been shown
      very useful in detecting a variety of targets including RNAs from Zika and Ebola
      viruses. The base complementation between the toehold switch and the trigger RNA
      also makes it sensitive to sequence variations. Design of toehold switches
      involves a series of considerations related to their sequence properties,
      structures and specificities. Results: Here we present the first comprehensive
      web tool for designing toehold switches. We also propose a score for predicting
      the efficacy of designed toehold switches based on properties learned from ~180
      experimentally tested switches. Availability and implementation: The toehold
      switch web tool is available at https://yiplab.cse.cuhk.edu.hk/toehold/.

PMID- 29648574
TI  - Association of Frailty with Recovery from Disability among Community-Dwelling
      Older Adults: Results from Two Large U.S. Cohorts.
AB  - Background: Disability in activities of daily living (ADLs) is a dynamic process
      and transitions among different disability states are common. However, little is
      known about factors affecting recovery from disability. We examined the
      association between frailty and recovery from disability among non-disabled
      community-dwelling elders. Methods: We studied 1023 adults from the
      Cardiovascular Health Study (CHS) and 685 adults from the Health and Retirement
      Study (HRS), who were >=65 years and had incident disability, defined as having
      difficulty in >=1 ADL (dressing, eating, toileting, bathing, transferring,
      walking across a room). Disability recovery was defined as having no difficulty
      in any ADLs. Frailty was assessed by slowness, weakness, exhaustion, inactivity,
      and shrinking. Persons were classified as "non-frail" (0 criteria), "prefrail" (1
      2 criteria), or "frail" (3-5 criteria). Results: In total, 539 (52.7%) CHS
      participants recovered from disability within one year. Almost two-thirds of non
      frail persons recovered, while less than two-fifths of the frail recovered. In
      the HRS, 234 (34.2%) participants recovered from disability within two years.
      Approximately half of the non-frail recovered, while less than one-fifth of the
      frail recovered. After adjustment, prefrail and frail CHS participants were 16%
      and 36% less likely to recover than the non-frail, respectively. In the HRS,
      frail persons had a 41% lower likelihood of recovery than the non-frail.
      Conclusions: Frailty is an independent predictor of poor recovery from disability
      among non-disabled older adults. These findings validate frailty as a marker of
      decreased resilience and may offer opportunities for individualized interventions
      and geriatric care based on frailty assessment.

PMID- 29648575
TI  - Early evolutionary divergence between papillary and anaplastic thyroid cancers.
AB  - Background: Papillary thyroid cancer (PTC) is the most common thyroid carcinoma
      and exhibits an almost uniformly good prognosis, while anaplastic thyroid cancer
      (ATC) is less frequent and is one of the most aggressive cancers usually
      resistant to conventional treatment. Current hypothesis posits that ATC derives
      from PTC through the progressive acquisition of a discrete number of genomic
      alterations and implies that the mutational landscape of ATC resembles that of
      PTC. However, the clinical behaviour of ATC and PTC is radically different. We
      decided to address the disconnection between the clinical behaviour of ATC and
      PTC and the proposed model of the progressive development of ATC from PTC.
      Patients and methods: We carried out exome sequencing of DNA from 14 ATC
      specimens including three cases of concomitant ATC and PTC as well as their
      corresponding normal DNA from 14 patients. The sequencing results were validated
      using droplet digital PCR. We carried out immunohistochemistry and
      immunofluorescence studies of the concomitant ATC and PTC cases. In addition, we
      integrated our sequencing results with the existing TCGA data. Results: Most of
      the somatic mutations identified in the ATC component differed from the ones in
      PTC in the cases of concomitant ATC and PTC. The trunks of the phylogenetic trees
      representing the somatic mutations were short with long branches. In one case of
      concomitant PTC and ATC specimens, we observed an infiltration of PTC cells
      within the ATC component. Moreover, we integrated our results with data obtained
      from TCGA and observed that the most frequent mutations found in ATC presented
      high cancer cell fraction values and were significantly different from the PTC
      ones. Conclusion: ATC diverge from PTC early in tumour development and both
      tumour types evolve independently. Our work allows the understanding of the
      relationship between ATC and PTC facilitating the clinical management of these
      malignancies.

PMID- 29648577
TI  - Purchasing silence.

PMID- 29648576
TI  - Life-space mobility in Parkinson's disease: Associations with motor and non-motor
      symptoms.
AB  - Background: To describe life-space mobility and explore associations of motor and
      non-motor symptoms with life-space mobility in people with Parkinson's disease
      (PD). Methods: 164 community-dwelling persons with PD (mean age 71.6 years, 64.6%
      men) received a postal survey and a subsequent home visit. Motor assessments
      included perceived walking difficulties (Walk-12G), mobility (Timed Up and Go
      test), motor symptoms (UPDRS-III) and freezing of gait (item 3, FOG-Qsa). Non
      motor symptoms included depressive symptoms (GDS-15), pain, fatigue (NHP-EN) and
      global cognition (MoCA). Life-space mobility was assessed with the life-space
      assessment (LSA). Calculations included composite score (range 0-120; higher
      indicating better life-space mobility), independent life-space (range 0-5),
      assisted life-space (range 0-5), and maximal life-space (range 0-5). Associations
      were analyzed with linear regression models, adjusted for age, sex, and PD
      severity (Hoehn and Yahr). Results: Mean life-space mobility score was 72.3 (SD
      28.8). Almost all participants (90 %) reached the highest life-space level
      (beyond town). Half of these reached this level independently, while one-third
      were unable to move outside their bedroom without assistive devices or personal
      help. When adjusted for confounders, depressive symptoms, pain, and perceived
      walking difficulties was negatively associated with life-space mobility. In the
      multivariable model, only perceived walking difficulties was associated with life
      space mobility. Conclusions: Our findings indicate that perceived walking
      difficulties should be targeted to maintain or improve life-space mobility in
      people with PD. Depressive symptoms and pain may also merit consideration. More
      research is needed to elucidate the role of environmental and personal factors
      for life-space mobility in PD.

PMID- 29648578
TI  - Gastric Adenocarcinoma of the Fundic Gland Type: Update and Literature Review.
AB  - Objectives: Gastric adenocarcinoma of the fundic gland type (GA-FG) is a newly
      described entity with a lack of awareness amongst general surgical pathologists
      and this review highlights the key features and controversies associated with
      this uncommon neoplasm. Methods: A literature search through PubMed using
      synonyms for GA-FG was conducted to obtain 111 cases. Results: GA-FG is a well
      differentiated neoplasm of oxyntic mucosa, that is comprised of chief cells and
      parietal cells. Chief cell differentiation is highlighted with Muc-6, RUNX3, and
      pepsinogen. Parietal cells are highlighted with H+/K+ ATPase and PDGFRA-alpha.
      Association with Helicobacter infection, chronic gastritis, intestinal
      metaplasia, or gastric atrophy is not seen. Most GA-FGs are confined to the
      mucosa. Deeper invasion, lymphovascular invasion, nodal metastasis, and
      extragastric spread are uncommon. Conclusions: GA-FGs are rare lesions that
      typically follow a benign course. However, despite features of malignancy in some
      cases, complete surgical excision, sometimes with endoscopic mucosal resection,
      seems adequate treatment.

PMID- 29648579
TI  - Capn4 contributes to tumor invasion and metastasis in clear cell renal cell
      carcinoma cells via modulating talin-focal adhesion kinase signaling pathway.
AB  - Calpain small subunit 1 (Capn4) has been shown to correlate with the
      metastasis/invasion of clear cell renal cell carcinoma (ccRCC). This study aimed
      to further elucidate the molecular mechanisms underlying Capn4-mediated ccRCC
      progression. The mRNA expression levels in ccRCC cells were measured by
      quantitative real-time PCR. The effects of Capn4 on cell adhesion, invasion, and
      migration were examined by cell adhesion assay, cell invasion assay, and wound
      healing assay, respectively. The protein levels were detected by western blot
      analysis. The effect of Capn4 on cancer metastasis in vivo was assessed in a nude
      mice xenograft model. It was found that Capn4 was up-regulated in the ccRCC
      cells, and Capn4 overexpression suppressed cell adhesion activity and increased
      cell invasion and migration in 786-O cells, while Capn4 silencing increased cell
      adhesion activity and impaired the invasion and migration ability of Caki-1
      cells. Capn4 overexpression also increased the protein level of cleaved talin in
      786-O cells, while Capn4 silencing decreased the protein level of cleaved talin
      in Caki-1 cells. The focal adhesion kinase (FAK)/AKT/MAPK signaling was activated
      by Capn4 overexpression in 786-O cells, and was inhibited by Capn4 down
      regulation in Caki-1 cells. Capn4 overexpression increased the protein levels of
      matrix metalloproteinase 2 (MMP-2), vimentin, N-cadherin, and down-regulated E
      cadherin in 786-O cells, while Capn4 silencing decreased the protein levels of
      MMP-2, vimentin, N-cadherin, and up-regulated E-cadherin in Caki-1 cells. Capn4
      also promoted cancer metastasis in the in vivo nude mice xenograft model. Our
      results implicate the functional role of Capn4 in ccRCC invasion and migration,
      which may contribute to cancer metastasis in ccRCC.

PMID- 29648580
TI  - Bevacizumab plus hypofractionated radiotherapy versus radiotherapy alone in
      elderly patients with glioblastoma: the randomized, open-label, phase II ARTE
      trial.
AB  - Background: The addition of bevacizumab to temozolomide-based chemoradiotherapy
      (TMZ/RT -> TMZ) did not prolong overall survival (OS) in patients with newly
      diagnosed glioblastoma in phase III trials. Elderly and frail patients are
      underrepresented in clinical trials, but early reports suggested preferential
      benefit in this population. Patients and methods: ARTE was a 2 : 1 randomized,
      multi-center, open-label, non-comparative phase II trial of hypofractionated RT
      (40 Gy in 15 fractions) with bevacizumab (10 mg/kg*14 days) (arm A, N = 50) or
      without bevacizumab (arm B, N = 25) in patients with newly diagnosed glioblastoma
      aged >=65 years. The primary objective was to obtain evidence for prolongation of
      median OS by the addition of bevacizumab to RT. Response was assessed by RANO
      criteria. Quality of life (QoL) was monitored by the EORTC QLQ-C30/BN20 modules.
      Exploratory studies included molecular subtyping by 450k whole methylome and gene
      expression analyses. Results: Median PFS was longer in arm A than in arm B (7.6
      and 4.8 months, P = 0.003), but OS was similar (12.1 and 12.2 months, P = 0.77).
      Clinical deterioration was delayed and more patients came off steroids in arm A.
      Prolonged PFS in arm A was confined to tumors with the receptor tyrosine kinase
      (RTK) I methylation subtype (HR 0.25, P = 0.014) and proneural gene expression
      (HR 0.29, P = 0.025). In a Cox model of OS controlling for established prognostic
      factors, associations with more favorable outcome were identified for age <70
      years (HR 0.52, P = 0.018) and Karnofsky performance score 90%-100% (HR 0.51, P =
      0.026). Including molecular subtypes into that model identified an association of
      the RTK II gene methylation subtype with inferior OS (HR 1.73, P = 0.076).
      Conclusion: Efficacy outcomes and exploratory analyses of ARTE do not support the
      hypothesis that the addition of bevacizumab to RT generally prolongs survival in
      elderly glioblastoma patients. Molecular biomarkers may identify patients with
      preferential benefit from bevacizumab. Clinical trial registration number:
      NCT01443676.

PMID- 29648582
TI  - Inference of the human polyadenylation code.
AB  - Motivation: Processing of transcripts at the 3'-end involves cleavage at a
      polyadenylation site followed by the addition of a poly(A)-tail. By selecting
      which site is cleaved, the process of alternative polyadenylation enables genes
      to produce transcript isoforms with different 3'-ends. To facilitate the
      identification and treatment of disease-causing mutations that affect
      polyadenylation and to understand the sequence determinants underlying this
      regulatory process, a computational model that can accurately predict
      polyadenylation patterns from genomic features is desirable. Results: Previous
      works have focused on identifying candidate polyadenylation sites and classifying
      tissue-specific sites. By training on how multiple sites in genes are
      competitively selected for polyadenylation from 3'-end sequencing data, we
      developed a deep learning model that can predict the tissue-specific strength of
      a polyadenylation site in the 3' untranslated region of the human genome given
      only its genomic sequence. We demonstrate the model's broad utility on multiple
      tasks, without any application-specific training. The model can be used to
      predict which polyadenylation site is more likely to be selected in genes with
      multiple sites. It can be used to scan the 3' untranslated region to find
      candidate polyadenylation sites. It can be used to classify the pathogenicity of
      variants near annotated polyadenylation sites in ClinVar. It can also be used to
      anticipate the effect of antisense oligonucleotide experiments to redirect
      polyadenylation. We provide analysis on how different features affect the model's
      predictive performance and a method to identify sensitive regions of the genome
      at the single-based resolution that can affect polyadenylation regulation.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 29648581
TI  - Multiple sclerosis lesions affect intrinsic functional connectivity of the spinal
      cord.
AB  - Patients with multiple sclerosis present with focal lesions throughout the spinal
      cord. There is a clinical need for non-invasive measurements of spinal cord
      activity and functional organization in multiple sclerosis, given the cord's
      critical role in the disease. Recent reports of spontaneous blood oxygenation
      level-dependent fluctuations in the spinal cord using functional MRI suggest
      that, like the brain, cord activity at rest is organized into distinct,
      synchronized functional networks among grey matter regions, likely related to
      motor and sensory systems. Previous studies looking at stimulus-evoked activity
      in the spinal cord of patients with multiple sclerosis have demonstrated
      increased levels of activation as well as a more bilateral distribution of
      activity compared to controls. Functional connectivity studies of brain networks
      in multiple sclerosis have revealed widespread alterations, which may take on a
      dynamic trajectory over the course of the disease, with compensatory increases in
      connectivity followed by decreases associated with structural damage. We build
      upon this literature by examining functional connectivity in the spinal cord of
      patients with multiple sclerosis. Using ultra-high field 7 T imaging along with
      processing strategies for robust spinal cord functional MRI and lesion
      identification, the present study assessed functional connectivity within
      cervical cord grey matter of patients with relapsing-remitting multiple sclerosis
      (n = 22) compared to a large sample of healthy controls (n = 56). Patient
      anatomical images were rated for lesions by three independent raters, with
      consensus ratings revealing 19 of 22 patients presented with lesions somewhere in
      the imaged volume. Linear mixed models were used to assess effects of lesion
      location on functional connectivity. Analysis in control subjects demonstrated a
      robust pattern of connectivity among ventral grey matter regions as well as a
      distinct network among dorsal regions. A gender effect was also observed in
      controls whereby females demonstrated higher ventral network connectivity.
      Wilcoxon rank-sum tests detected no differences in average connectivity or power
      of low frequency fluctuations in patients compared to controls. The presence of
      lesions was, however, associated with local alterations in connectivity with
      differential effects depending on columnar location. The patient results suggest
      that spinal cord functional networks are generally intact in relapsing-remitting
      multiple sclerosis but that lesions are associated with focal abnormalities in
      intrinsic connectivity. These findings are discussed in light of the current
      literature on spinal cord functional MRI and the potential neurological
      underpinnings.

PMID- 29648584
TI  - The American College of Cardiology 2018; a Starbuckian ODYSSEY and a Black
      Barbershop.

PMID- 29648583
TI  - LipidPedia: a comprehensive lipid knowledgebase.
AB  - Motivation: Lipids are divided into fatty acyls, glycerolipids,
      glycerophospholipids, sphingolipids, saccharolipids, sterols, prenol lipids and
      polyketides. Fatty acyls and glycerolipids are commonly used as energy storage,
      whereas glycerophospholipids, sphingolipids, sterols and saccharolipids are
      common used as components of cell membranes. Lipids in fatty acyls,
      glycerophospholipids, sphingolipids and sterols classes play important roles in
      signaling. Although more than 36 million lipids can be identified or
      computationally generated, no single lipid database provides comprehensive
      information on lipids. Furthermore, the complex systematic or common names of
      lipids make the discovery of related information challenging. Results: Here, we
      present LipidPedia, a comprehensive lipid knowledgebase. The content of this
      database is derived from integrating annotation data with full-text mining of
      3923 lipids and more than 400 000 annotations of associated diseases, pathways,
      functions and locations that are essential for interpreting lipid functions and
      mechanisms from over 1 400 000 scientific publications. Each lipid in LipidPedia
      also has its own entry containing a text summary curated from the most frequently
      cited diseases, pathways, genes, locations, functions, lipids and experimental
      models in the biomedical literature. LipidPedia aims to provide an overall
      synopsis of lipids to summarize lipid annotations and provide a detailed listing
      of references for understanding complex lipid functions and mechanisms.
      Availability and implementation: LipidPedia is available at
      http://lipidpedia.cmdm.tw. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29648585
TI  - Interspecies conflict affects RNA expression.
AB  - Predation is an extreme form of competition between bacteria, involving the
      secretion of antimicrobial substances by predators, often packaged within outer
      membrane vesicles (OMVs). Recent studies into the Myxococcus xanthus/Escherichia
      coli predator/prey relationship have illuminated transcriptional changes during
      predation, identifying likely targets of predatory attack in the prey and
      nutrient assimilation strategies of the predator. Abundant non-coding RNAs can be
      observed in the predator and prey transcriptomes, with evidence of predation
      dependent regulation of RNA levels. Given the observed secretion of regulatory
      RNAs within OMVs by bacteria, it will next be exciting to test whether the
      intercellular trafficking of regulatory RNAs is employed by predator and/or prey
      in their survival struggles.

PMID- 29648587
TI  - Characterisation of the ruminal fermentation and microbiome in lambs supplemented
      with hydrolysable and condensed tannins.
AB  - This study characterised the response of ruminal fermentation and the rumen
      microbiome in lambs fed commercial vegetal sources of hydrolysable tannins (HT)
      and condensed tannins (CT). Forty-four lambs (19.56 +/- 2.06 kg) were randomly
      assigned to either a concentrate diet (CON, n = 8) or CON supplemented with 4% of
      two HT [chestnut (Castanea sativa, HT-c) and tara (Caesalpinia spinosa, HT-t)]
      and CT [mimosa (Acacia negra, CT-m) and gambier (Uncaria gambir, CT-g)] extracts
      (all, n = 9) for 75 days pre-slaughter. Tannin supplementation did not influence
      ruminal fermentation traits. Quantitative PCR demonstrated that tannins did not
      affect the absolute abundance of ruminal bacteria or fungi. However, CT-m (
      12.8%) and CT-g (-11.5%) significantly reduced the abundance of methanogens,
      while HT-t (-20.7%) and CT-g (-20.8%) inhibited protozoal abundance. Ribosomal
      amplicon sequencing revealed that tannins caused changes in the phylogenetic
      structure of the bacterial and methanogen communities. Tannins inhibited the
      fibrolytic bacterium, Fibrobacter and tended to suppress the methanogen genus,
      Methanosphaera. Results demonstrated that both HT and CT sources could impact the
      ruminal microbiome when supplemented at 4% inclusion level. HT-t, CT-m and CT-g
      extracts displayed specific antimicrobial activity against methanogens and
      protozoa without compromising ruminal fermentation in a long-term feeding trial.

PMID- 29648586
TI  - Direct loop-mediated isothermal amplification assay for on-site detection of
      Staphylococcus aureus.
AB  - Staphylococcus aureus (S. aureus) is a major human pathogen that may produce a
      variety of toxins and cause staphylococcal food poisoning. In the present study,
      a direct loop-mediated isothermal amplification (LAMP) assay was developed and
      validated to detect S. aureus in food samples. Without prior cultural enrichment
      and DNA extraction steps, bacterial DNA was released by heating at 100 degrees C
      for 5 min and directly subjected to LAMP assay. Using a set of LAMP primers
      recognizing six distinct regions of nuc gene, the developed direct LAMP assay was
      highly specific, and the analytical sensitivity was determined to be 7.6 * 102
      CFU/mL. Moreover, with the pre-mixed LAMP reagents stored at -20 degrees C, the
      entire assay should be finished within 40 min. These features greatly simplified
      the operating procedure and made the direct LAMP a powerful tool for rapid and on
      site detection of S. aureus in food samples.

PMID- 29648588
TI  - Influence of three-dimensional lung epithelial cells and interspecies
      interactions on antibiotic efficacy against Mycobacterium abscessus and
      Pseudomonas aeruginosa.
AB  - Mycobacterium abscessus lung infection is a major health problem for cystic
      fibrosis (CF) patients. Understanding the in vivo factors that influence the
      outcome of therapy may help addressing the poor correlation between in vitro and
      in vivo antibiotic efficacy. We evaluated the influence of interspecies
      interactions and lung epithelial cells on antibiotic efficacy. Therefore, single
      and dual-species biofilms of M. abscessus and a major CF pathogen (Pseudomonas
      aeruginosa) were cultured on a plastic surface or on in vivo-like three
      dimensional (3-D) lung epithelial cells, and the activity of antibiotics
      (colistin, amikacin, clarithromycin, ceftazidime) in inhibiting biofilm formation
      was evaluated. Using the most physiologically relevant model (dual-species
      biofilms on 3-D cells), we observed that treatment with antibiotics during
      biofilm development inhibited P. aeruginosa but not M. abscessus biofilms,
      resulting in a competitive advantage for the latter. Clarithromycin efficacy
      against P. aeruginosa was inhibited by 3-D lung cells. In addition, biofilm
      induction of M. abscessus was observed by certain antibiotics on plastic but not
      on 3-D cells. Pseudomonas aeruginosa influenced the efficacy of certain
      antibiotics against M. abscessus, but not vice versa. In conclusion, these
      results suggest a role of host cells and interspecies interactions in bacterial
      responses to antimicrobials.

PMID- 29648589
TI  - Analysis of the 3H8 antigen of Candida albicans reveals new aspects of the
      organization of fungal cell wall proteins.
AB  - The walls of both, yeast and mycelial cells of Candida albicans possess a species
      specific antigen that is recognized by a monoclonal antibody (MAb 3H8). This
      antigen can be extracted in the form of a very high Mr complex, close or over 106
      Da, by treatment, with beta-1,3-glucanase, beta mercaptoethanol or dithothreitol,
      or mild alkali, but not by saturated hydrogen fluoride (HF) in pyridine,
      suggesting that the complex is bound to wall beta-1,3 glucans, and to proteins by
      disulfide bonds, but not to beta-1,6 glucans. Through its sensitivity to trypsin
      and different deglycosylation procedures, it was concluded that the epitope is
      associated to a glycoprotein containing N-glycosidic, but not O-glycosidic mannan
      moieties. By means of electrophoresis in polycrylamide gradient gels, followed by
      mass spectrometric analysis, the epitope was pinpointed to a very high MW complex
      containing Agglutinin-Like Sequence (ALS) family proteins, and other cytoplasmic,
      membrane and secreted proteins. The components of this complex are bound by
      unknown covalent bonds. The material extracted with beta mercaptoethanol or
      dilute alkali appeared under the electron microscope as large aggregates in the
      form of spheroidal and mostly web-like structures of large sizes. These, and
      additional data, suggest that this protein complex may constitute an important
      part of the basic glycoprotein structure of C. albicans. The possibility that
      similar complexes exist in the wall of other fungi is an attractive, although yet
      untested possibility.

PMID- 29648590
TI  - Sequence modification of the master regulator Pdr1 interferes with its
      transcriptional autoregulation and confers altered azole resistance in Candida
      glabrata.
AB  - The transcriptional regulator Pdr1 plays a positive role in regulating azole drug
      resistance in Candida glabrata. Previous studies have shown the importance of the
      carboxyl (C)-terminal sequence of Pdr1 in fulfilling its function, as this region
      mediates interactions between Pdr1 and the co-activator Gal11A and is crucial for
      activation of Pdr1 targets. However, mechanisms of how Pdr1 is regulated,
      especially implication of its C-terminus in the regulatory activity, remain
      uncharacterized. In this study, we unexpectedly observed that the C-terminal
      modification of Pdr1 in an azole-resistant clinical isolate harboring a single
      GOF mutation, resulted in adverse effects such as decreased expression levels of
      Pdr1, downregulation of Pdr1 targets and azole hypersensitivity. Importantly, the
      C-terminal 3 * FLAG tagging significantly decreased the binding of Pdr1 to the
      pleiotropic drug response elements in its own promoter, promoted an irregular
      cellular mislocalization and thereby disrupted the transcriptional autoregulation
      of this master regulator. Unexpectedly, the aberrant cytoplasmic localization
      caused a non-functional interaction with Gal11A, a co-activator involved in drug
      resistance. Based on these findings, we proposed that C-terminal sequence of Pdr1
      is vital for its stability and functionality, and targeting regulation of this
      region may represent a promising future strategy for combating C. glabrata
      infection and drug resistance.

PMID- 29648591
TI  - Analysis of the effect of temperature on protein abundance in Demodex-associated
      Bacillus oleronius.
AB  - A potential role for bacteria in the induction of rosacea has been suggested. The
      aim of this work was to characterise the effect of temperature on the production
      of immunostimulatory proteins by Bacillus oleronius-a bacterium to which rosacea
      patients show sera reactivity and which was originally isolated from a Demodex
      mite from a rosacea patient. The affected skin of rosacea patients is at a higher
      temperature than unaffected skin, and it was postulated that this might alter the
      protein expression pattern of B. oleronius. B. oleronius growth was reduced at 37
      degrees C compared to 30 degrees C but resulted in increased expression of the
      immune-reactive 62kDa protein (1.65 fold [P < 0.05]). Proteomic analysis revealed
      increased abundance of a wide range of proteins involved in the stress response
      (e.g. stress proteins [21.7-fold increase], phosphocarrier protein HPr [438.5
      fold increase], 60 kDa chaperonin [12.6-fold increase]). Proteins decreased in
      abundance after growth at 37 degrees C included ferredoxin (325-fold decrease)
      and peptidase (244-fold decrease). This work indicates that the increased skin
      temperature of rosacea patients may alter the growth and protein production
      pattern of B. oleronius and lead to the greater production of immuo-stimulatory
      proteins.

PMID- 29648592
TI  - Yeast 2.0-connecting the dots in the construction of the world's first functional
      synthetic eukaryotic genome.
AB  - Historians of the future may well describe 2018 as the year that the world's
      first functional synthetic eukaryotic genome became a reality. Without the
      benefit of hindsight, it might be hard to completely grasp the long-term
      significance of a breakthrough moment in the history of science like this. The
      role of synthetic biology in the imminent birth of a budding Saccharomyces
      cerevisiae yeast cell carrying 16 man-made chromosomes causes the world of
      science to teeter on the threshold of a future-defining scientific frontier. The
      genome-engineering tools and technologies currently being developed to produce
      the ultimate yeast genome will irreversibly connect the dots between our improved
      understanding of the fundamentals of a complex cell containing its DNA in a
      specialised nucleus and the application of bioengineered eukaryotes designed for
      advanced biomanufacturing of beneficial products. By joining up the dots between
      the findings and learnings from the international Synthetic Yeast Genome project
      (known as the Yeast 2.0 or Sc2.0 project) and concurrent advancements in
      biodesign tools and smart data-intensive technologies, a future world powered by
      a thriving bioeconomy seems realistic. This global project demonstrates how a
      collaborative network of dot connectors-driven by a tinkerer's indomitable
      curiosity to understand how things work inside a eukaryotic cell-are using
      cutting-edge biodesign concepts and synthetic biology tools to advance science
      and to positively frame human futures (i.e. improved quality of life) in a
      planetary context (i.e. a sustainable environment). Explorations such as this
      have a rich history of resulting in unexpected discoveries and unanticipated
      applications for the benefit of people and planet. However, we must learn from
      past explorations into controversial futuristic sciences and ensure that
      researchers at the forefront of an emerging science such as synthetic biology
      remain connected to all stakeholders' concerns about the biosafety, bioethics and
      regulatory aspects of their pioneering work. This article presents a shared
      vision of constructing a synthetic eukaryotic genome in a safe model organism by
      using novel concepts and advanced technologies. This multidisciplinary and
      collaborative project is conducted under a sound governance structure that does
      not only respect the scientific achievements and lessons from the past, but that
      is also focussed on leading the present and helping to secure a brighter future
      for all.

PMID- 29648593
TI  - Validity and reliability of the Turkish version of the European Health Literacy
      Survey Questionnaire.
AB  - Health literacy is a public health priority which refers to individual's
      knowledge, motivation and competence to access, understand, appraise and apply
      health information to prevent disease and promote health in daily life. This
      study aimed to adapt European Health Literacy Survey Questionnaire (HLS-EU-Q47)
      into Turkish and to investigate its psychometric properties. The questionnaire
      was translated into Turkish by using both group translation and expert opinion
      methods. Forward translation-back translation method was used for language
      validity and the final Turkish version (HLS-TR) was formed. HLS-EU-Q47 and Health
      Awareness Scale (HAS) were administered to 505 respondents. The scale reliability
      was examined using Crohnbach's alpha coefficient and the construct validity was
      assessed by principal axis factoring procedure. The convergent validity was
      obtained by Pearson correlation coefficients between HLS-TR and HAS scores and
      discriminant validity was examined comparing the scores of participants who were
      stratified according to ages, educational status, gender, general health status
      and social status. Cronbach's alpha coefficient for the whole scale was 0.95.
      Principal axis factoring extracted nine factors which eigenvalues were >1 and
      explained 50.01% of total variance. Factor matrix displayed that all items gave
      greater load in factor 1, showing that health literacy measured with one factor.
      Positive and significant correlation was found between HLS-TR and HAS.
      Significant relations were found between HLS-TR scores and selected determinants
      of health. This study revealed that the HLS-TR was a valid and reliable measuring
      instrument with appropriate psychometric characteristics.

PMID- 29648594
TI  - Active Case Finding for Communicable Diseases in Prison Settings: Increasing
      Testing Coverage and Uptake Among the Prison Population in the European
      Union/European Economic Area.
AB  - Prison populations are disproportionally affected by communicable diseases when
      compared with the general community because of a complex mix of socioeconomic
      determinants and environmental factors. Tailored and adequate health care
      provision in prisons has the potential to reach vulnerable and underserved groups
      and address their complex needs. We investigated the available evidence on
      modalities and effectiveness of active case-finding interventions in prisons by
      searching PubMed, Embase, and the Cochrane Library for records on prison and
      active case finding with no language limit. Conference abstracts and unpublished
      research reports also were retrieved. We analyzed the findings by testing
      modality, outcomes, and study quality. The included 90 records-63 peer-reviewed,
      26 from gray literature, and 1 systematic review-reported variously on viral
      hepatitis, human immunodeficiency virus, sexually transmitted infections, and
      tuberculosis. No records were retrieved for other communicable diseases. Provider
      initiated opt-in testing was the most frequently investigated modality. Testing
      at entry and provider-initiated testing were reported to result in comparatively
      higher uptake ranges. However, no comparative studies were identified that
      reported statistically significant differences between testing modalities.
      Positivity rates among tested inmates ranged broadly but were generally high for
      all diseases. The evidence on active case finding in correctional facilities is
      limited, heterogeneous, and of low quality, making it challenging to draw
      conclusions on the effect of different testing modalities. Scale-up of provider
      initiated testing in European correctional facilities could substantially reduce
      the undiagnosed fraction and, hence, prevent additional disease transmission in
      both prison settings and the community at large.

PMID- 29648595
TI  - Progesterone as a Postnatal Prophylactic Agent for Encephalopathy Caused by
      Prenatal Hypoxic Ischemic Insult.
AB  - Brain damage caused by hypoxic ischemic insult during the perinatal period causes
      hypoxic ischemic encephalopathies (HIEs). Therapeutic hypothermia is indicated
      for HIE, but because the therapeutic burden is large for its limited therapeutic
      effectiveness, another strategy is needed. Progesterone (P4) plays a
      neuroprotective role through the actions of its metabolite, allopregnanolone
      (Allo), on P4 receptor, gamma-aminobutyric acid type A receptors or both. We
      examined the therapeutic potential of P4 using a newborn rat model of HIE. Fetal
      rats were exposed to transient ischemic hypoxia by 30-minute bilateral uterine
      artery clamping on gestational day 18. After spontaneous birth, newborn pups were
      subcutaneously injected with P4 (0.10 or 0.01 mg), medroxyprogesterone acetate
      (MPA; 0.12 mg), or Allo (0.10 mg) through postnatal days (PDs) 1 to 9. Brain
      damage in the rats was assessed using the rotarod test at PD50. The HIE insult
      reduced the rats' ability in the rotarod task, which was completely reversed by
      P4 and Allo, but not by MPA. Histological examination revealed that the HIE
      insult decreased neuronal (the cortex and the hippocampal CA1 region) and
      oligodendroglial cell density (the corpus callosum) through PD0 to PD50. The axon
      fiber density and myelin sheath thickness in the corpus callosum were also
      reduced at PD50. The time-course study revealed that P4 restored oligodendroglial
      cells by PD5, which was followed by neuroprotective action of P4 that lasted long
      over the injection period. These results suggest that P4 protects the neonatal
      brain from HIE insult via restoration of oligodendroglial cells.

PMID- 29648597
TI  - Secondary bile acids inhibit Candida albicans growth and morphogenesis.
AB  - Candida albicans is one of the most common causes of fungal infections in humans
      with a significant mortality rate. However, the factors involved in C. albicans
      gastrointestinal (GI) colonization remain unclear. We hypothesize that secondary
      bile acids have direct antifungal activity against C. albicans and may play a
      critical role in maintaining GI colonization resistance against C. albicans. In
      this study, we investigated the effect of secondary bile acids including
      lithocholic acid (LCA) and deoxycholic acid (DCA) on C. albicans growth and
      morphogenesis. Results indicate that LCA and DCA at in vivo cecal micelle
      concentrations inhibit C. albicans growth in vitro. Interestingly, LCA and DCA
      also significantly inhibited the germ tube, hyphae and biofilm formation in C.
      albicans. In addition, pre-treatment of C. albicans with LCA and DCA
      significantly reduced the percentage of C. albicans cells attached to a colon
      cancer cell line. Collectively, our results demonstrate that secondary bile acids
      play an important role in controlling the growth and morphological switching of
      C. albicans. Results from this study demonstrate that secondary bile acid possess
      direct antifungal activity against C. albicans, explaining a potential mechanism
      for gastrointestinal colonization resistance against C. albicans.

PMID- 29648598
TI  - A New Brief Measure of Executive Function: Adapting the Head-Toes-Knees-Shoulders
      Task to Older Adults.
AB  - Background and Objectives: Executive function (EF) abilities are recognized as
      components of cognition most likely to show age-related declines. Measurement of
      EF in older adults is often computer-based, takes place in a laboratory setting,
      and thus lacks ecological validity. We sought to investigate a new way of
      measuring EF in older adults by adapting a brief, behavioral measure of EF in
      children, the Head-Toes-Knees-Shoulders task (HTKS). Research Design and Methods:
      A sample of 150 community-dwelling older adults (Mean age = 68.55, SD = 6.34)
      completed the HTKS, NIH Toolbox: Cognition Battery (NIHTB-CB) and Positive and
      Negative Affect Schedule. Results: The HTKS showed adequate internal consistency,
      alpha = .84. Significant associations between HTKS variables and measures of
      attention and inhibitory control were robust to the influences of age, processing
      speed, and subjective health ratings. HTKS completion time exhibited the
      strongest associations to NIHTB-CB measures, suggesting that the time it takes
      older adults to complete the HTKS may be a better measure of EF than the total
      score. Nonsignificant associations between HTKS variables and positive and
      negative affect demonstrated discriminant validity. Discussion and Implications:
      These results provide initial evidence for use of the HTKS as a brief, low-cost,
      easy to administer measure of EF in older adults. Further research is needed to
      determine its potential to identify individuals at risk for poor cognitive
      outcomes. A brief, valid measure may allow for wider screenings aimed at early
      intervention, when cognitive interventions are most effective.

PMID- 29648599
TI  - Polycystic Ovary Syndrome Is Associated With Adverse Mental Health and
      Neurodevelopmental Outcomes.
AB  - Context: Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism
      and subfertility, but the effects on mental health and child neurodevelopment are
      unclear. Objectives: To determine if (1) there is an association between PCOS and
      psychiatric outcomes and (2) whether rates of autism spectrum disorder (ASD) and
      attention deficit hyperactivity disorder (ADHD) are higher in children of mothers
      with PCOS. Design: Data were extracted from the Clinical Practice Research
      Datalink. Patients with PCOS were matched to two control sets (1:1) by age, body
      mass index, and primary care practice. Control set 2 was additionally matched on
      prior mental health status. Primary outcomes were the incidence of depression,
      anxiety, and bipolar disorder. Secondary outcomes were the prevalence of ADHD or
      ASD in the children. Results: Eligible patients (16,986) were identified; 16,938
      and 16,355 were matched to control sets 1 and 2, respectively. Compared with
      control set 1, baseline prevalence was 23.1% vs 19.3% for depression, 11.5% vs
      9.3% for anxiety, and 3.2% vs 1.5% for bipolar disorder (P < 0.001). The hazard
      ratio for time to each endpoint was 1.26 (95% confidence interval 1.19 to 1.32),
      1.20 (1.11 to 1.29), and 1.21 (1.03 to 1.42) for set 1 and 1.38 (1.30 to 1.45),
      1.39 (1.29 to 1.51), and 1.44 (1.21 to 1.71) for set 2. The odds ratios for ASD
      and ADHD in children were 1.54 (1.12 to 2.11) and 1.64 (1.16 to 2.33) for set 1
      and 1.76 (1.27 to 2.46) and 1.34 (0.96 to 1.89) for set 2. Conclusions: PCOS is
      associated with psychiatric morbidity and increased risk of ADHD and ASD in their
      children. Screening for mental health disorders should be considered during
      assessment.

PMID- 29648596
TI  - Unraveling synthesis of the cryptococcal cell wall and capsule.
AB  - Fungal pathogens cause devastating infections in millions of individuals each
      year, representing a huge but underappreciated burden on human health. One of
      these, the opportunistic fungus Cryptococcus neoformans, kills hundreds of
      thousands of patients annually, disproportionately affecting people in resource
      limited areas. This yeast is distinguished from other pathogenic fungi by a
      polysaccharide capsule that is displayed on the cell surface. The capsule
      consists of two complex polysaccharide polymers: a mannan substituted with xylose
      and glucuronic acid, and a galactan with galactomannan side chains that bear
      variable amounts of glucuronic acid and xylose. The cell wall, with which the
      capsule is associated, is a matrix of alpha and beta glucans, chitin, chitosan,
      and mannoproteins. In this review, we focus on synthesis of the wall and capsule,
      both of which are critical for the ability of this microbe to cause disease and
      are distinct from structures found in either model yeasts or the mammals
      afflicted by this infection. Significant research effort over the last few
      decades has been applied to defining the synthetic machinery of these two
      structures, including nucleotide sugar metabolism and transport,
      glycosyltransferase activities, polysaccharide export, and assembly and
      association of structural elements. Discoveries in this area have elucidated
      fundamental biology and may lead to novel targets for antifungal therapy. In this
      review, we summarize the progress made in this challenging and fascinating area,
      and outline future research questions.

PMID- 29648600
TI  - Comparison of two alternate PGF2alpha products in two estrus synchronization
      protocols in beef heifers.
AB  - Two experiments were conducted to evaluate the effects of a high concentrate,
      s.c. PGF2alpha compared with a conventionally concentrated, i.m. PGF2alpha in
      estrus synchronization protocols for heifers. In Exp. 1, 869 Angus-based beef
      heifers were enrolled at 8 locations. All heifers were exposed to the 7-d CO
      Synch + controlled internal drug release (CIDR) estrus synchronization protocol.
      On day 7 of the protocol heifers received 100 ug of GnRH i.m., and a CIDR insert
      for 7 d. On day 0, at CIDR removal, estrous detection patches were applied to
      heifers and, within location, heifers randomly received 1 of 2 PGF2alpha
      treatments: 5 mL of Lutalyse i.m. (CONTROL; n = 434) or a 2 mL of Lutalyse
      HighCon s.c. (HiCON; n = 435). A second GnRH injection was administered at 54 +/-
      2 h and heifers were fixed-time AI (TAI). Heifers were evaluated for estrous
      activity at TAI by determining the activation of estrous detection patches.
      Pregnancy rates to AI (PR/AI) were diagnosed by transrectal ultrasonography
      between 35 and 55 d after TAI. The percentage of heifers exhibiting estrus
      between day 0 and TAI did not differ (P = 0.68) between CONTROL and HiCON
      treatments (47 vs. 46 +/- 4%, respectively). Additionally, PR/AI were similar (P
      = 0.65) between CONTROL and HiCON treatments (46 vs. 45 +/- 3%). In Exp. 2, 190
      Angus-based beef heifers were enrolled at 2 locations. Heifers were exposed to
      the melengestrol acetate (MGA)-PGF2alpha protocol where they were offered 0.5 mg
      MGA per day from days 1 to 14. On day 33, heifers were randomly assigned to
      receive CONTROL (n = 95) or HiCON (n = 95) treatment, and estrous detection aids
      were applied. Heifers were exposed to AI 12 h after detection of estrus. Heifers
      not detected in estrus at location 1 received a second PGF2alpha injection 6 d
      after the initial PGF2alpha injection and were placed with fertile bulls. Heifers
      at location 2 that did not express estrus were administered 100 ug of GnRH i.m.
      and exposed to TAI 96 h after the initial PGF2alpha injection. Transrectal
      ultrasonography was used to diagnose PR/AI between 51 and 57 d after the initial
      PGF2alpha injection. The percentage of heifers exhibiting estrus during the
      estrus detection period was similar (P = 0.40) between CONTROL and HiCON
      treatments (82 vs. 87 +/- 4%). Furthermore, PR/AI were similar (P = 0.62) between
      CONTROL and HiCON treatments (60 vs. 65 +/- 5%). In summary, the 2 concentrations
      and corresponding routes of administration of PGF2alpha were similar in efficacy
      at synchronizing estrus in beef heifers.

PMID- 29648601
TI  - Compensating Injury to Autonomy in English Negligence Law: Inconsistent
      Recognition.
AB  - Recently in Shaw v Kovac, the Court of Appeal seemed to have rejected a
      standalone injury to autonomy (ITA) as actionable in negligence, in an informed
      consent case. In this article, I argue that Shaw can be explained away, and that
      English law recognizes ITA as actionable in a series of cases, some of which
      Bhamra, Tracey, and Yearworth-were not hitherto understood to do so. However, the
      under-theorization in the cases leads to inconsistencies. Like cases
      (Rees/Yearworth; Chester/Tracey) are not treated alike; ITA is misunderstood to
      be about 'religious offence' (Bhamra) and property loss (Yearworth) and worse
      still, the more serious type 2 ITA (Rees) gives rise to a weaker remedy (of
      exceptional nature aside) than the less serious type 1 injury (Chester). A better
      understanding of the different manifestations of ITA will lead to results which
      are both more consistent and more justified on the merit.

PMID- 29648604
TI  - UMLS to DBPedia link discovery through circular resolution.
AB  - Objective: The goal of this work is to map Unified Medical Language System (UMLS)
      concepts to DBpedia resources using widely accepted ontology relations from the
      Simple Knowledge Organization System (skos:exactMatch, skos:closeMatch) and from
      the Resource Description Framework Schema (rdfs:seeAlso), as a result of which a
      complete mapping from UMLS (UMLS 2016AA) to DBpedia (DBpedia 2015-10) is made
      publicly available that includes 221 690 skos:exactMatch, 26 276 skos:closeMatch,
      and 6 784 322 rdfs:seeAlso mappings. Methods: We propose a method called circular
      resolution that utilizes a combination of semantic annotators to map UMLS
      concepts to DBpedia resources. A set of annotators annotate definitions of UMLS
      concepts returning DBpedia resources while another set performs annotation on
      DBpedia resource abstracts returning UMLS concepts. Our pipeline aligns these 2
      sets of annotations to determine appropriate mappings from UMLS to DBpedia.
      Results: We evaluate our proposed method using structured data from the Wikidata
      knowledge base as the ground truth, which consists of 4899 already existing UMLS
      to DBpedia mappings. Our results show an 83% recall with 77% precision-at-one
      (P@1) in mapping UMLS concepts to DBpedia resources on this testing set.
      Conclusions: The proposed circular resolution method is a simple yet effective
      technique for linking UMLS concepts to DBpedia resources. Experiments using
      Wikidata-based ground truth reveal a high mapping accuracy. In addition to the
      complete UMLS mapping downloadable in n-triple format, we provide an online
      browser and a RESTful service to explore the mappings.

PMID- 29648602
TI  - Factors Associated With Prolonged Viral Shedding in Patients With Avian Influenza
      A(H7N9) Virus Infection.
AB  - Background: Data are limited on the impact of neuraminidase inhibitor (NAI)
      treatment on avian influenza A(H7N9) virus RNA shedding. Methods: In this
      multicenter, retrospective study, data were collected from adults hospitalized
      with A(H7N9) infection during 2013-2017 in China. We compared clinical features
      and A(H7N9) shedding among patients with different NAI doses and combination
      therapies and evaluated factors associated with A(H7N9) shedding, using Cox
      proportional hazards regression. Results: Among 478 patients, the median age was
      56 years, 71% were male, and 37% died. The median time from illness onset to NAI
      treatment initiation was 8 days (interquartile range [IQR], 6-10 days), and the
      median duration of A(H7N9) RNA detection from onset was 15.5 days (IQR, 12-20
      days). A(H7N9) RNA shedding was shorter in survivors than in patients who died (P
      < .001). Corticosteroid administration (hazard ratio [HR], 0.62 [95% confidence
      interval {CI}, .50-.77]) and delayed NAI treatment (HR, 0.90 [95% CI, .91-.96])
      were independent risk factors for prolonged A(H7N9) shedding. There was no
      significant difference in A(H7N9) shedding duration between NAI combination
      treatment and monotherapy (P = .65) or between standard-dose and double-dose
      oseltamivir treatment (P = .70). Conclusions: Corticosteroid therapy and delayed
      NAI treatment were associated with prolonged A(H7N9) RNA shedding. NAI
      combination therapy and double-dose oseltamivir treatment were not associated
      with a reduced A(H7N9) shedding duration as compared to standard-dose
      oseltamivir.

PMID- 29648603
TI  - PHYD prevents secondary dormancy establishment of seeds exposed to high
      temperature and is associated with lower PIL5 accumulation.
AB  - Dormancy cycling controls the seasonal conditions under which seeds germinate,
      and these conditions strongly influence growth and survival of plants. Several
      endogenous and environmental signals affect the dormancy status of seeds. Factors
      such as time, light, and temperature influence the balance between abscisic acid
      (ABA) and gibberellic acid (GA), two phytohormones that play a key role in seed
      dormancy and germination. High temperatures have been shown to increase ABA level
      and prevent seed germination, a process known as thermoinhibition. High
      temperature can also cause the acquisition of secondary dormancy, preventing
      germination of seeds upon their return to favorable germination conditions. The
      mechanisms and conditions linking thermoinhibition and secondary dormancy remain
      unclear. Phytochromes are photoreceptors known to promote seed germination of
      many plant species including Arabidopsis thaliana. Here, we demonstrate a role
      for PHYD in modulating secondary dormancy acquisition in seeds exposed to high
      temperature. We found that a functional PHYD gene is required for the germination
      of seeds that experienced high temperature, and that ABA- and GA-related gene
      expression during and after pre-incubation at high temperatures was altered in a
      phyD mutant. We further show that the level of PHYD mRNA increased in seeds pre
      incubated at high temperature and that this increase correlates with efficient
      removal of the germination repressor PIL5.

PMID- 29648605
TI  - Lexical analysis suggests differences between subgroups in anxieties over
      radiation exposure in Fukushima.
AB  - Although many experts have attempted communication about radiation risk, fears
      about radiation exposure stemming from the Fukushima Daiichi Nuclear Power Plant
      accident remain deeply rooted. The characteristics of the anxiety vary with
      social background, which makes it difficult to alleviate with one approach. Our
      ultimate goal is therefore to create risk-communication materials tailored to
      various groups with differing social backgrounds. Towards that end, the purpose
      of the present study was to clarify potential factors associated with radiation
      related anxieties within these groups. After obtaining informed consent, we
      conducted focus group interviews (FGIs) with Fukushima residents from various
      social groups, including evacuees, emergency responders, government personnel,
      medical staff, and decontamination workers. We obtained narrative comments
      specifically related to the following two themes: (i) lessons learned (at work or
      home) in light of one's position in society, and (ii) health issues. After
      transcribing the comments, we examined potential factors associated with
      radiation-related anxieties using both quantitative and qualitative study methods
      simultaneously, using the KH Coder software and the Steps for Coding and
      Theorization (SCAT) method respectively. FGIs were undertaken with 141 persons.
      Categories, words and storylines extracted in this study might indicate potential
      anxieties that are unique to each group, but our analysis also suggested that
      some anxieties were common to all groups. We expect to continue the analyses and,
      ultimately, to establish group-tailored risk-communication materials for
      achieving our final goal of adapting and better managing risk-communication
      efforts to help people deal more effectively with the scientific, technological
      and societal changes that came about after the disaster.

PMID- 29648607
TI  - NICE public health guidance update.

PMID- 29648606
TI  - ECD1 functions as an RNA-editing trans-factor of rps14-149 in plastids and is
      required for early chloroplast development in seedlings.
AB  - Chloroplast development is a highly complex process and the regulatory mechanisms
      have not yet been fully characterized. In this study, we identified Early
      Chloroplast Development 1 (ECD1), a chloroplast-localized pentatricopeptide
      repeat protein (PPR) belonging to the PLS subfamily. Inactivation of ECD1 in
      Arabidopsis led to embryo lethality, and abnormal embryogenesis occurred in
      ecd1/+ heterozygous plants. A decrease in ECD1 expression induced by RNAi
      resulted in seedlings with albino cotyledons but normal true leaves. The aberrant
      morphology and under-developed thylakoid membrane system in cotyledons of RNAi
      seedlings suggests a role of ECD1 specifically in chloroplast development in
      seedlings. In cotyledons of ECD1-RNAi plants, RNA-editing of rps14-149 (encoding
      ribosomal protein S14) was seriously impaired. In addition, dramatically
      decreased plastid-encoded RNA polymerase-dependent gene expression and abnormal
      chloroplast rRNA processing were also observed. Taken together, our results
      indicate that ECD1 is indispensable for chloroplast development at the seedling
      stage in Arabidopsis.

PMID- 29648608
TI  - RAB39A: a Rab small GTPase with a prominent role in cancer stemness.
AB  - RAB39A is a Rab small GTPase that localizes at distinct subcellular compartments
      and regulates intracellular membrane trafficking pathways in vertebrate cells.
      RAB39A interacts with various molecules and modulates vesicular trafficking that
      regulates multiple biological pathways such as neuronal differentiation and/or
      autophagy. Among these pathways are Hippo and Notch signallings, microtubular
      organization and mitophagy/autophagy. Although RAB39A has never been studied in
      cancer biology, it has been recently shown to promote cancer stemness and
      tumorigenesis. Molecular pathways regulated by RAB39A are transcriptionally
      maintained by the formation of molecular complex with RXRB, NCOR and HDAC that
      also contribute to cancer stemness. In this review, we provide current knowledge
      on the oncogenic function of RAB39A and summarize the effect of different
      microenvironments on RAB39A activity and subcellular localization in cancer
      cells.

PMID- 29648609
TI  - Elite UK winter wheat cultivars differ in their ability to support the
      colonization of beneficial root-infecting fungi.
AB  - In numerous countries, Gaeumannomyces species, within the Magnaporthaceae family,
      have previously been implicated in the suppression of take-all root disease in
      wheat. A UK arable isolate collection (n=47) was gathered and shown to contain
      Gaeumannomyces hyphopodioides and an unnamed Magnaporthaceae species. A novel
      seedling pot bioassay revealed that both species had a similar ability to
      colonize cereal roots; however, rye (Secale cereale) was only poorly colonized by
      the Magnaporthaceae species. To evaluate the ability of 40 elite UK winter wheat
      cultivars to support soil inoculum of beneficial soil-dwelling fungi, two field
      experiments were carried out using a naturally infested arable site in south-east
      England. The elite cultivars grown in the first wheat situation differed in their
      ability to support G. hyphopodioides inoculum, measured by colonization on
      Hereward as the subsequent wheat in a seedling soil core bioassay. In addition,
      the root colonization ability of G. hyphopodioides was influenced by the choice
      of the second wheat cultivar. Nine cultivars supported the colonization of the
      beneficial root fungus. Our findings provide evidence of complex host genotype-G.
      hyphopodioides interactions occurring under field conditions. This new knowledge
      could provide an additional soil-based crop genetic management strategy to help
      combat take-all root disease.

PMID- 29648610
TI  - Chiron: translating nanopore raw signal directly into nucleotide sequence using
      deep learning.
AB  - Sequencing by translocating DNA fragments through an array of nanopores is a
      rapidly maturing technology that offers faster and cheaper sequencing than other
      approaches. However, accurately deciphering the DNA sequence from the noisy and
      complex electrical signal is challenging. Here, we report Chiron, the first deep
      learning model to achieve end-to-end basecalling and directly translate the raw
      signal to DNA sequence without the error-prone segmentation step. Trained with
      only a small set of 4,000 reads, we show that our model provides state-of-the-art
      basecalling accuracy, even on previously unseen species. Chiron achieves
      basecalling speeds of more than 2,000 bases per second using desktop computer
      graphics processing units.

PMID- 29648612
TI  - Analysis of Escherichia coli STs and resistance mechanisms in sewage from
      Islamabad, Pakistan indicates a difference in E. coli carriage types between
      South Asia and Europe.
AB  - Objectives: To discover the Escherichia coli STs and associated resistance
      mechanisms in the community in Islamabad, Pakistan by analysis of E. coli
      isolates in sewage. Methods: One hundred and ten E. coli were isolated from
      sewage across the city of Islamabad without antibiotic bias and confirmed as E.
      coli by MALDI-TOF MS. Isolates were characterized by fumC/fimH (CH) typing and
      core-genome MLST. Resistance mechanisms, virulence genes, phylotypes and plasmid
      incompatibility types were determined in a subset of isolates by in silico
      analysis. The genomic position of blaCTX-M-15 was determined using S1-PFGE,
      probing and Nanopore MinION sequencing. Results and conclusions: The most
      prevalent STs were ST394, ST10 and ST648, accounting for 39% of all isolates
      collected and were found at many sites across Islamabad. Carbapenemase genes were
      absent and only a single isolate of ST131 was found. The most prevalent
      resistance mechanisms were qnrS1 and blaCTX-M-15, with blaCTX-M-15 penetrating
      many STs and found in 31% of all collected isolates. However, the majority of the
      successful STs were blaCTX-M-15 negative indicating that resistance is not the
      main driver of prevalence. Twenty-three percent of blaCTX-M-15 genes were
      chromosomally encoded and large ISEcp1-mediated insertions included qnrS1 and
      several plasmid genes. In all chromosomally encoded isolates no plasmid copies of
      blaCTX-M-15 were found. The most prevalent ST (ST394) contained many
      enteroaggregative E. coli virulence genes and the fimH30 variant allele
      previously linked to the success of ST131.

PMID- 29648611
TI  - Fine Mapping the Interaction Between Dendritic Cell-Specific Intercellular
      Adhesion Molecule (ICAM)-3-Grabbing Nonintegrin and the Cytomegalovirus Envelope
      Glycoprotein B.
AB  - Background: Human cytomegalovirus (HCMV) is a leading cause of virally induced
      congenital disorders and morbidities in immunocompromised individuals, ie,
      transplant, cancer, or acquired immune deficiency syndrome patients. Human
      cytomegalovirus infects virtually all cell types through the envelope
      glycoprotein complex gH/gL/gO with or without a contribution of the pentameric
      gH/gL/pUL128L. Together with gH/gL, the HCMV envelope glycoprotein B (gB)
      contributes to the viral fusion machinery. Methods: We previously showed that gB
      is a ligand for the C-type lectin dendritic cell-specific intercellular adhesion
      molecule-3-grabbing nonintegrin (DC-SIGN) contributing to HCMV attachment to and
      infection of DC-SIGN-expressing cells. However, the features of the DC-SIGN/gB
      interaction remain unclear. To address this point, the role of glycans on gB and
      the consequences of mutagenesis and antibody-mediated blockades on both partners
      were examined in this study. Results: We identified DC-SIGN amino acid residues
      involved in this interaction through an extensive mutagenesis study. We also
      showed the importance of high-mannose N-glycans decorating the asparagine residue
      at position 208, demonstrating that the antigenic domain 5 on gB is involved in
      the interaction with DC-SIGN. Finally, antibody-mediated blockades allowed us to
      identify DC-SIGN as a major HCMV attachment receptor on monocyte-derived
      dendritic cells. Conclusions: Taken together, these results have permitted us to
      fine-map the interaction between DC-SIGN and HCMV gB.

PMID- 29648613
TI  - Trending on Pinterest: an examination of pins about skin tanning.
AB  - Rates of melanoma and nonmelanoma skin cancers are on the rise in the USA with
      data revealing disproportionate increase in female young adults. The popularity
      of intentional skin tanning among U.S. adolescents is attributed to several
      factors, including prioritization of physical appearance, media images of tanned
      celebrities, ease of availability of artificial tanning facilities, and more
      recently, the prevalence and celebration of tanned skin on social media.
      Pinterest, as the third most popular social media platform, was searched for
      "pins" about skin tanning. The resultant "pins" were examined to understand the
      extent and characteristics of skin tanning portrayed on Pinterest. We analyzed
      pins on Pinterest about skin tanning (n = 501) through a quantitative content
      analysis. Overall, results indicated an overwhelmingly protanning characteristic
      of pins about skin tanning on Pinterest, with over 85% of pins promoting tanning
      behavior. The pins were generally characterized by the portrayal of a female
      subject (61%) and provided positive reinforcement for tanning (49%). Use of
      tanning for enhancing appearance was the main positive outcome expectancy
      portrayed in the pins (35%), and nudity or exposure of skin on arms (32%) and
      legs (31%) was evident in about a third of pins. With overwhelmingly positive
      pins promoting tanning, use of female subjects, exhibiting nudity, and appearance
      enhancement, there seems be to a consistent targeting of female users to accept
      tanning as a socially acceptable and popular behavior. The findings indicate a
      need for developing sun protection messages and the leveraging of social media
      for dissemination of skin cancer prevention and detection messages.

PMID- 29648615
TI  - A multicomponent behavioral intervention for smoking cessation during pregnancy:
      a nonconcurrent multiple-baseline design.
AB  - Given serious consequences of maternal smoking, we aimed to develop and test a
      multicomponent behavioral intervention to enhance smoking cessation during
      pregnancy. In this nonconcurrent, multiple-baseline intervention pilot study, 48
      daily smoking pregnant women (mean 13.7 weeks of gestation) were recruited from
      Buffalo, NY, USA. Upon completion of the repeated baseline smoking monitoring (up
      to 3 weeks), 30 continuous smokers received a contingent financial incentive
      based intervention with three additional components (education and counseling,
      monitoring and feedback, and family support). After the quit date, participants
      met with counselors (~1 hr/visit) daily for 2 weeks and twice a week for another
      6 weeks. Twenty-one out of 30 participants quit smoking completely (verified by
      urine cotinine) after receiving the intervention, and the other nine nonquitters
      decreased smoking substantially. The estimated smoking cessation rate was 70.0%
      (21/30) at the second week of the intervention, and 63.3% (19/30) at the
      conclusion of the 8-week intervention assuming the dropouts as smoking. In
      interrupted time series analysis, the mean daily number of cigarettes smoked
      among quitters decreased by 6.52, 5.34, and 4.67 among early, delayed, and late
      intervention groups, respectively. Quitters' mean urine cotinine level maintained
      stably high before the intervention but decreased rapidly to the nonsmoking range
      once the intervention was initiated. Most participants (85.7%) reported meeting
      or exceeding expectations, and 100% would recommend the program to others. This
      pilot multicomponent intervention was feasible and acceptable to most
      participants, resulting in a high smoking cessation rate among pregnant smokers
      who were unlikely to quit spontaneously.

PMID- 29648614
TI  - Overexpression of OsPGIP2 confers Sclerotinia sclerotiorum resistance in Brassica
      napus through increased activation of defense mechanisms.
AB  - Sclerotinia stem rot (SSR), caused by Sclerotinia sclerotiorum, is the most
      serious disease affecting the yield of the agriculturally and economically
      important crop Brassica napus (rapeseed). In this study, Oryza sativa
      polygalacturonase-inhibiting protein 2 (OsPGIP2) was found to effectively
      enhanced rapeseed immunity against S. sclerotiorum infection. Leaf extracts of B.
      napus plants overexpressing OsPGIP2 showed enhanced S. sclerotiorum resistance by
      delaying pathogen infection. The constitutive expression of OsPGIP2 in rapeseed
      plants provided a rapid and effective defense response, which included the
      production of reactive oxygen species, interactions with S. sclerotiorum
      polygalacturonases (SsPG3 and SsPG6), and effects on the expression of defense
      genes. RNA sequencing analysis revealed that the pathogen induced many
      differentially expressed genes associated with pathogen recognition, redox
      homeostasis, mitogen-activated protein kinase signaling cascades, hormone
      signaling pathways, pathogen-/defense-related genes, and cell wall-related genes.
      The overexpression of OsPGIP2 also led to constitutively increased cell wall
      cellulose and hemicellulose contents in stems without compromising seed quality.
      The results demonstrate that OsPGIP2 plays a major role in rapeseed defense
      mechanisms, and we propose a model for OsPGIP2-conferred resistance to S.
      sclerotiorum in these plants.

PMID- 29648616
TI  - Sustained benefits of delaying school start time on adolescent sleep and well
      being.
AB  - Study Objectives: To investigate the short- and longer-term impact of a 45-min
      delay in school start time on sleep and well-being of adolescents. Methods: The
      sample consisted of 375 students in grades 7-10 (mean age +/- SD: 14.6 +/- 1.15
      years) from an all-girls' secondary school in Singapore that delayed its start
      time from 07:30 to 08:15. Self-reports of sleep timing, sleepiness, and well
      being (depressive symptoms and mood) were obtained at baseline prior to the
      delay, and at approximately 1 and 9 months after the delay. Total sleep time
      (TST) was evaluated via actigraphy. Results: After 1 month, bedtimes on school
      nights were delayed by 9.0 min, while rise times were delayed by 31.6 min,
      resulting in an increase in time in bed (TIB) of 23.2 min. After 9 months, the
      increase in TIB was sustained, and TST increased by 10.0 min relative to
      baseline. Participants also reported lower levels of subjective sleepiness and
      improvement in well-being at both follow-ups. Notably, greater increase in sleep
      duration on school nights was associated with greater improvement in alertness
      and well-being. Conclusions: Delaying school start time can result in sustained
      benefits on sleep duration, daytime alertness, and mental well-being even within
      a culture where trading sleep for academic success is widespread.

PMID- 29648617
TI  - Society of Behavioral Medicine (SBM) position statement: Enact taxes on sugar
      sweetened beverages to prevent chronic disease.
AB  - The Society of Behavioral Medicine (SBM) encourages stakeholders to implement a
      sugar sweetened beverage excise tax. Sugar sweetened beverages are the largest
      source of added sugars in the USA and have detrimental effects on population
      health by increasing risks for chronic diseases. Based on existing research
      evidence, SBM supports an excise tax equivalent to at least 20% to meaningfully
      affect consumption patterns. As evidenced by research studies in Mexico and the
      USA, sugar sweetened beverage taxes can have positive impacts on population
      health and can raise significant tax revenue. To avoid potential unintended
      consequences that may arise from taxes to improve diet-related behaviors, it is
      important to monitor industry and consumer behavior in response to the tax.

PMID- 29648619
TI  - Impact of warming, moderate nitrogen addition and bark herbivory on BVOC
      emissions and growth of Scots pine (Pinus sylvestris L.) seedlings.
AB  - The changing climate will expose boreal forests to rising temperatures,
      increasing soil nitrogen (N) levels and an increasing risk of herbivory. The
      single and interaction effects of warming (+2  degrees C increase), moderate N
      addition (30 kg ha-1 year-1) and bark herbivory by large pine weevil (Hylobius
      abietis L.) on growth and emissions of biogenic volatile organic compounds
      (BVOCs) from shoots of Scots pine (Pinus sylvestris L.) seedlings were studied in
      growth chambers over 175 days. In addition, warming and N addition effects on
      shoot net photosynthesis (Pn) were measured. Nitrogen addition increased both
      shoot and root dry weights, whereas warming, in combination with herbivory,
      reduced stem height growth. Warming together with N addition increased current
      year shoot Pn, whereas N effects on previous-year shoot Pn were variable over
      time. Warming decreased non-oxygenated monoterpene (MT) emissions in June and
      increased them in July. Of individual MT compounds, alpha-pinene, delta-3-carene,
      gamma-terpinene and terpinolene were among the most frequently responsive
      compounds in warming treatments in the May-July period. Sesquiterpene emissions
      were observed only from warming treatments in July. Moderate N addition increased
      oxygenated monoterpenes in May, and MTs in June and September. However, N
      addition effect on MTs in June was clearer without warming than with warming.
      Bark herbivory tended to increase MT emissions in combination with warming and N
      addition 3 weeks after the damage caused by weevils. Of individual compounds in
      other BVOC blends, herbivory increased the emissions of methyl-benzene, benzene
      and hexanal in July. Hence, though both warming and N addition have a potential
      to change BVOC emissions from Scots pines, the N effect may also be partly
      cancelled by warming. Furthermore, herbivory pressure in combination with climate
      warming and N addition may, at least periodically, increase BVOC release to the
      atmosphere from young Scots pine seedlings.

PMID- 29648618
TI  - Inflammation in Schizophrenia: Pathogenetic Aspects and Therapeutic
      Considerations.
AB  - This paper discusses the current evidence from animal and human studies for a
      central role of inflammation in schizophrenia. In animal models, pre- or
      perinatal elicitation of the immune response may increase immune reactivity
      throughout life, and similar findings have been described in humans. Levels of
      pro-inflammatory markers, such as cytokines, have been found to be increased in
      the blood and cerebrospinal fluid of patients with schizophrenia. Numerous
      epidemiological and clinical studies have provided evidence that various
      infectious agents are risk factors for schizophrenia and other psychoses. For
      example, a large-scale epidemiological study performed in Denmark clearly showed
      that severe infections and autoimmune disorders are such risk factors. The
      vulnerability-stress-inflammation model may help to explain the role of
      inflammation in schizophrenia because stress can increase pro-inflammatory
      cytokines and may even contribute to a chronic pro-inflammatory state.
      Schizophrenia is characterized by risk genes that promote inflammation and by
      environmental stress factors and alterations of the immune system. Typical
      alterations of dopaminergic, serotonergic, noradrenergic, and glutamatergic
      neurotransmission described in schizophrenia have also been found in low-level
      neuroinflammation and consequently may be key factors in the generation of
      schizophrenia symptoms. Further support for the relevance of a low-level
      neuroinflammatory process in schizophrenia is provided by the loss of central
      nervous system volume and microglial activation demonstrated in neuroimaging
      studies. Last but not least, the benefit of anti-inflammatory medications found
      in some studies and the intrinsic anti-inflammatory and immunomodulatory effects
      of antipsychotics provide further support for the role of inflammation in this
      debilitating disease.

PMID- 29648621
TI  - The MEF2 transcriptional target DMPK induces loss of sarcomere structure and
      cardiomyopathy.
AB  - Aims: The pathology of heart failure is characterized by poorly contracting and
      dilated ventricles. At the cellular level, this is associated with lengthening of
      individual cardiomyocytes and loss of sarcomeres. While it is known that the
      transcription factor myocyte enhancer factor-2 (MEF2) is involved in this
      cardiomyocyte remodelling, the underlying mechanism remains to be elucidated.
      Here, we aim to mechanistically link MEF2 target genes with loss of sarcomeres
      during cardiomyocyte remodelling. Methods and results: Neonatal rat
      cardiomyocytes overexpressing MEF2 elongated and lost their sarcomeric structure.
      We identified myotonic dystrophy protein kinase (DMPK) as direct MEF2 target gene
      involved in this process. Adenoviral overexpression of DMPK E, the isoform
      upregulated in heart failure, resulted in severe loss of sarcomeres in vitro, and
      transgenic mice overexpressing DMPK E displayed disruption of sarcomere structure
      and cardiomyopathy in vivo. Moreover, we found a decreased expression of
      sarcomeric genes following DMPK E gain-of-function. These genes are targets of
      the transcription factor serum response factor (SRF) and we found that DMPK E
      acts as inhibitor of SRF transcriptional activity. Conclusion: Our data indicate
      that MEF2-induced loss of sarcomeres is mediated by DMPK via a decrease in
      sarcomeric gene expression by interfering with SRF transcriptional activity.
      Together, these results demonstrate an unexpected role for DMPK as a direct
      mediator of adverse cardiomyocyte remodelling and heart failure.

PMID- 29648620
TI  - Comparative transcriptome analysis in Arabidopsis ein2/ore3 and ahk3/ore12
      mutants during dark-induced leaf senescence.
AB  - Leaf senescence involves degenerative but active biological processes that
      require balanced regulation of pro- and anti-senescing activities. Ethylene and
      cytokinin are major antagonistic regulatory hormones that control the timing and
      progression rate of leaf senescence. To identify the roles of these hormones in
      the regulation of leaf senescence in Arabidopsis, global gene expression profiles
      in detached leaves of the wild type, an ethylene-insensitive mutant (ein2/ore3),
      and a constitutive cytokinin response mutant (ahk3/ore12) were investigated
      during dark-induced leaf senescence. Comparative transcriptome analyses revealed
      that genes involved in oxidative or salt stress response were preferentially
      altered in the ein2/ore3 mutant, whereas genes involved in ribosome biogenesis
      were affected in the ahk3/ore12 mutant during dark-induced leaf senescence.
      Similar results were also obtained for developmental senescence. Through
      extensive molecular and physiological analyses in ein2/ore3 and ahk3/ore12 during
      dark-induced leaf senescence, together with responses when treated with cytokinin
      and ethylene inhibitor, we conclude that ethylene acts as a senescence-promoting
      factor via the transcriptional regulation of stress-related responses, whereas
      cytokinin acts as an anti-senescing agent by maintaining cellular activities and
      preserving the translational machinery. These findings provide new insights into
      how plants utilize two antagonistic hormones, ethylene and cytokinin, to regulate
      the molecular programming of leaf senescence.

PMID- 29648622
TI  - Deep learning of genomic variation and regulatory network data.
AB  - The human genome is now investigated through high-throughput functional assays,
      and through the generation of population genomic data. These advances support the
      identification of functional genetic variants and the prediction of traits (e.g.
      deleterious variants and disease). This review summarizes lessons learned from
      the large-scale analyses of genome and exome data sets, modeling of population
      data and machine-learning strategies to solve complex genomic sequence regions.
      The review also portrays the rapid adoption of artificial intelligence/deep
      neural networks in genomics; in particular, deep learning approaches are well
      suited to model the complex dependencies in the regulatory landscape of the
      genome, and to provide predictors for genetic variant calling and interpretation.

PMID- 29648623
TI  - Bipartite graphs in systems biology and medicine: a survey of methods and
      applications.
AB  - The latest advances in high-throughput techniques during the past decade allowed
      the systems biology field to expand significantly. Today, the focus of biologists
      has shifted from the study of individual biological components to the study of
      complex biological systems and their dynamics at a larger scale. Through the
      discovery of novel bioentity relationships, researchers reveal new information
      about biological functions and processes. Graphs are widely used to represent
      bioentities such as proteins, genes, small molecules, ligands, and others such as
      nodes and their connections as edges within a network. In this review, special
      focus is given to the usability of bipartite graphs and their impact on the field
      of network biology and medicine. Furthermore, their topological properties and
      how these can be applied to certain biological case studies are discussed.
      Finally, available methodologies and software are presented, and useful insights
      on how bipartite graphs can shape the path toward the solution of challenging
      biological problems are provided.

PMID- 29648624
TI  - Evaluation of Light Attraction for the Stored-Product Psocids, Liposcelis
      entomophila, Liposcelis paeta, and Liposcelis brunnea.
AB  - Psocids have become global pests of stored commodities as they can cause
      considerable economic losses. These insects are difficult to control because they
      have developed resistance to many chemical insecticides. Therefore, it is crucial
      to investigate alternative integrated pest management (IPM) approaches, such as
      the use of light attraction for monitoring and/or controlling psocids. Light
      attraction has been studied for Liposcelis bostrychophila Badonnel (Psocoptera:
      Liposcelididae) but not for other psocid species. In this study, we investigated
      the response of adults of three psocid species (Psocoptera: Liposcelididae),
      Liposcelis entomophila (Enderlein), Liposcelis paeta Pearman, and Liposcelis
      brunnea Motschulsky, to six wavelengths of light from light-emitting diode (LED)
      in paired-choice pitfall tests. L. entomophila females and males were not
      attracted to any of the wavelengths tested. L. paeta females responded positively
      to two ultraviolet (UV) wavelengths (351 and 400 nm) and to green light (527 nm),
      while males did not respond to any light. L. brunnea females and males responded
      positively to all six wavelengths evaluated. Most of the LEDs that elicited
      positive responses to L. paeta females and L. brunnea females and males were also
      preferred when these lights were presented against brewer's yeast, a food
      attractant highly preferred by several psocid species. Females of L. paeta and L.
      brunnea were attracted to white light when compared with a blank, but females of
      L. entomophila were not attracted to white light compared to a blank.

PMID- 29648625
TI  - Corrigendum to 'Prognostic value of 3-dimensional echocardiographical heart
      volume assessment in patients scheduled for left ventricular assist device
      implantation' [Eur J Cardiothorac Surg doi:10.1093/ejcts/ezy002].

PMID- 29648627
TI  - Late outcomes of subcostal exchange of the HeartMate II left ventricular assist
      device: a word of caution.
AB  - OBJECTIVES: Previous studies have shown the usefulness of the subcostal exchange
      of the HeartMate II left ventricular assist device for device malfunction.
      However, long-term data are still limited. METHODS: Between March 2004 and July
      2017, 41 of 568 (7.2%) patients who had received a HeartMate II implant at our
      institution had a device exchange via a subcostal incision. We summarized early
      and late outcomes. RESULTS: Forty-one patients had a total of 48 subcostal pump
      exchanges. Indications for device exchange included device thrombosis (n = 31,
      76%), driveline infection (n = 2, 5%) and driveline injury (n = 8, 19%). All of
      the procedures were successful, and there were no in-hospital deaths. A Kaplan
      Meier survival curve showed 30-day and 1-year survival rates after subcostal
      exchange of 100% and 94.6%, respectively. However, 10 (25%) patients had left
      ventricular assist device-related infections following subcostal exchange that
      included 7 pump pocket infections and 3 driveline infections. Freedom from left
      ventricular assist device-related infection at 1 year after subcostal exchange
      was 79.3%. Thirteen (32%) patients had device malfunction due to pump thrombosis
      that required a 2nd device exchange. Seven patients had recurrent thrombosis.
      Three (7%) patients had a stroke. Freedom from device thrombosis and from a
      stroke event at 1 year was 74.4%. CONCLUSIONS: Subcostal pump exchange can be
      safely performed. However, there is a substantial risk of infection and recurrent
      thrombosis. Careful follow-up for late complications is mandatory.

PMID- 29648626
TI  - Regulation of Intracellular Triiodothyronine Is Essential for Optimal Macrophage
      Function.
AB  - Innate immune cells, including macrophages, have recently been identified as
      target cells for thyroid hormone. We hypothesized that optimal intracellular
      concentrations of the active thyroid hormone triiodothyronine (T3) are essential
      for proinflammatory macrophage function. T3 is generated intracellularly by type
      2 deiodinase (D2) and acts via the nuclear thyroid hormone receptor (TR). In
      zebrafish embryos, D2 knockdown increased mortality during pneumococcal
      meningitis. Primary murine D2 knockout macrophages exhibited impaired
      phagocytosis and partially reduced cytokine response to stimulation with
      bacterial endotoxin. These effects are presumably due to reduced intracellular T3
      availability. Knockdown of the main TR in macrophages, TRalpha, impaired
      polarization into proinflammatory macrophages and amplified polarization into
      immunomodulatory macrophages. Intracellular T3 availability and action appear to
      play a crucial role in macrophage function. Our data suggest that low
      intracellular T3 action has an anti-inflammatory effect, possibly due to an
      effect on macrophage polarization mediated via the TRalpha. This study provides
      important insights into the link between the endocrine and innate immune system.

PMID- 29648628
TI  - The Serosal Immune System of the Thorax in Toxicology.
AB  - The thoracic cavities receive increasing attention in toxicology, because inhaled
      fibers and (nano)particles can reach these cavities and challenge the local
      lymphoid tissues. The thoracic and abdominopelvic cavities are controlled by the
      serosal immune system with its special, loosely organized lymphoid clusters,
      namely the fat-associated lymphoid clusters and milky spots, which together can
      be denoted as serosa-associated lymphoid clusters. These clusters house numerous
      innate lymphoid cells, namely the nonconventional, innate B lymphoid cell and
      innate lymphocyte type 2 populations. The fat depots in the thorax play a
      significant role in the serosal immunity, and they can be modulated by health
      issues such as metabolic syndrome. The serosal immune system operates in a unique
      way at the interface of the innate and acquired immunity and therefore exposure
      related modulation of the system may have a distinct impact on the body's
      immunity. To add to the investigation of the serosal immune system in the thorax,
      this review describes the (micro)anatomy of the immune system in relation to
      exposure, with a focus on the rat and mouse as preferred species in toxicology
      and immunology.

PMID- 29648629
TI  - Antibiotic pressure on the acquisition and loss of antibiotic resistance genes in
      Klebsiella pneumoniae.
AB  - Objectives: In this study, we characterize a concurrent disseminated infection
      with a virulent hypermucoviscous (HMV) Klebsiella pneumoniae and an OXA-181
      producing XDR K. pneumoniae from a patient with recent hospitalization in India.
      During exposure to meropenem therapy, the highly susceptible HMV K. pneumoniae
      became resistant to carbapenems, consistent with the acquisition of blaOXA-181.
      Methods: Twelve K. pneumoniae isolates were recovered from the patient and the
      hospital room environment over a 3 month hospitalization. Phenotypic and
      molecular studies were completed to characterize the isolates. Oxford Nanopore
      and Illumina MiSeq WGS were performed to study phylogeny (MLST and SNPs),
      plasmids and virulence genes and demonstrate changes in the organism's resistome
      that occurred over time. Results: WGS revealed that the HMV K. pneumoniae
      belonged to ST23 and harboured an IncH1B virulence plasmid, while the XDR K.
      pneumoniae belonged to ST147 and possessed two MDR plasmids (IncR and IncFII),
      the blaOXA-181-bearing ColKP3 plasmid and chromosomal mutations conferring the
      XDR phenotype. Sequential isolates demonstrated plasmid diversification (fusion
      of the IncR and IncFII plasmids), mobilization of resistance elements (ompK35
      inactivation by ISEcp1-blaCTX-M-15 mobilization, varying numbers of resistance
      genes on plasmid scaffolds) and chromosomal mutations (mutations in mgrB) leading
      to further antibiotic resistance that coincided with antibiotic pressure.
      Importantly, the HMV strain in this study was unable to preserve the carbapenem
      resistant phenotype without the selective pressure of meropenem. Conclusions: To
      the best of our knowledge, we are the first to report a carbapenem-resistant HMV
      K. pneumoniae strain in the USA. Ultimately, this case demonstrates the role of
      antibiotic pressure in the acquisition and loss of important genetic elements.

PMID- 29648630
TI  - Identification of Prosthetic Joint Infection Pathogens Using a Shotgun
      Metagenomics Approach.
AB  - Background: Metagenomic shotgun sequencing has the potential to change how many
      infections, particularly those caused by difficult-to-culture organisms, are
      diagnosed. Metagenomics was used to investigate prosthetic joint infections
      (PJIs), where pathogen detection can be challenging. Methods: Four hundred eight
      sonicate fluid samples generated from resected hip and knee arthroplasties were
      tested, including 213 from subjects with infections and 195 from subjects without
      infection. Samples were enriched for microbial DNA using the MolYsis basic kit,
      whole-genome amplified, and sequenced using Illumina HiSeq 2500 instruments. A
      pipeline was designed to screen out human reads and analyze remaining sequences
      for microbial content using the Livermore Metagenomics Analysis Toolkit and
      MetaPhlAn2 tools. Results: When compared to sonicate fluid culture, metagenomics
      was able to identify known pathogens in 94.8% (109/115) of culture-positive PJIs,
      with additional potential pathogens detected in 9.6% (11/115). New potential
      pathogens were detected in 43.9% (43/98) of culture-negative PJIs, 21 of which
      had no other positive culture sources from which these microorganisms had been
      detected. Detection of microorganisms in samples from uninfected aseptic failure
      cases was conversely rare (7/195 [3.6%] cases). The presence of human and
      contaminant microbial DNA from reagents was a challenge, as previously reported.
      Conclusions: Metagenomic shotgun sequencing is a powerful tool to identify a wide
      range of PJI pathogens, including difficult-to-detect pathogens in culture
      negative infections.

PMID- 29648631
TI  - Myocardial tissue characteristics undoubtedly differ by gender but not age.

PMID- 29648633
TI  - Inhibition of A-Type K+ Channels by Urotensin-II Induces Sensory Neuronal
      Hyperexcitability Through the PKCalpha-ERK Pathway.
AB  - Previous studies have implicated urotensin-II in the nociception of sensory
      neurons. However, to date the relevant mechanisms remain unknown. In the current
      study we determined the role of urotensin-II in the regulation of transient
      outward A-type potassium currents (IA) and neuronal excitability in trigeminal
      ganglion (TG) neurons. We found that application of urotensin-II to small
      diameter TG neurons decreased IA in a dose-dependent manner, whereas the delayed
      rectifier potassium current was unaffected. The IA decrease induced by urotensin
      II depended on the urotensin-II receptor (UT-R) and was associated with a
      hyperpolarizing shift in the steady-state inactivation curve. Exposure of TG
      cells to urotensin-II markedly increased protein kinase C (PKC) activity, and PKC
      inhibition eliminated the UT-R-mediated IA decrease. Antagonism of PKCalpha,
      either pharmacologically or genetically, but not of PKCbeta prevented the
      decrease in IA induced by urotensin-II. Analysis of phospho-extracellular signal
      regulated kinase (p-ERK) revealed that urotensin-II significantly increased the
      expression level of p-ERK, whereas p-p38 and p-c-Jun N-terminal kinase remained
      unchanged. Inhibition of mitogen-activated protein kinase/ERK signaling by the
      kinase antagonist U0126 and PD98059 completely abolished the UT-R-mediated IA
      decrease. Moreover, urotensin-II significantly increased the action potential
      firing rate of small TG neurons; pretreatment with 4-aminopyridine prevented this
      effect. In summary, our findings suggest that urotensin-II selectively attenuated
      IA through stimulation of the PKCalpha-dependent ERK1/2 signaling pathway. This
      UT-R-dependent mechanism might contribute to neuronal hyperexcitability in TG
      neurons.

PMID- 29648634
TI  - Personalizing therapy for atrial fibrillation: the role of stem cell and in
      silico disease models.
AB  - Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated
      with substantial morbidity. There is considerable inter-patient variability in
      the pathologic processes that promote AF, and this variability likely has a
      significant genetic basis. Clinically this is reflected by the observation that
      anti-arrhythmic drugs and interventional procedures have highly variable
      efficacy, and this highlights the need for adopting a more efficacious
      personalized approach. We explore recent advancements in both in silico and stem
      cell disease models that set the stage for a personalized approach. Specifically
      we highlight new mechanistic insights in AF; the future role of computational
      models in planning personalized ablation strategies; the potential role of stem
      cell models as a preclinical platform for drug development; and the potential to
      use gene-editing technology to create patient-specific stem cell models. Finally,
      we introduce the concept of integrating stem cell models with computational
      modelling to create a novel pipeline for patient-specific drug discovery and
      development.

PMID- 29648635
TI  - A slowly growing mass in the left chest wall: additive value of real time
      myocardial contrast echocardiography.

PMID- 29648636
TI  - The root-knot nematode Meloidogyne incognita produces a functional mimic of the
      Arabidopsis INFLORESCENCE DEFICIENT IN ABSCISSION signaling peptide.
AB  - INFLORESCENCE DEFICIENT IN ABSCISSION (IDA) is a signaling peptide that regulates
      cell separation in Arabidopsis including floral organ abscission and lateral root
      emergence. IDA is highly conserved in dicotyledonous flowering plant genomes. IDA
      like sequences were also found in the genomic sequences of root-knot nematodes,
      Meloidogyne spp., which are globally deleterious pathogens of agriculturally
      important plants, but the role of these genes is unknown. Exogenous treatment of
      the Arabidopsis ida mutant with synthetic peptide identical to the M. incognita
      IDA-like 1 (MiIDL1) protein sequence minus its N-terminal signal peptide
      recovered both the abscission and root architecture defects. Constitutive
      expression of the full-length MiIDL1 open reading frame in the ida mutant
      substantially recovered the delayed floral organ abscission phenotype whereas
      transformants expressing a construct missing the MiIDL1 signal peptide retained
      the delayed abscission phenotype. Importantly, wild-type Arabidopsis plants
      harboring an MiIDL1-RNAi construct and infected with nematodes had approximately
      40% fewer galls per root than control plants. Thus, the MiIDL1 gene produces a
      functional IDA mimic that appears to play a role in successful gall development
      on Arabidopsis roots.

PMID- 29648638
TI  - Ovulatory Induction of SCG2 in Human, Nonhuman Primate, and Rodent Granulosa
      Cells Stimulates Ovarian Angiogenesis.
AB  - The luteinizing hormone (LH) surge is essential for ovulation, but the
      intrafollicular factors induced by LH that mediate ovulatory processes (e.g.,
      angiogenesis) are poorly understood, especially in women. The role of
      secretogranin II (SCG2) and its cleaved bioactive peptide, secretoneurin (SN),
      were investigated as potential mediators of ovulation by testing the hypothesis
      that SCG2/SN is induced in granulosa cells by human chorionic gonadotropin (hCG),
      via a downstream LH receptor signaling mechanism, and stimulates ovarian
      angiogenesis. Humans, nonhuman primates, and rodents were treated with hCG in
      vivo resulting in a significant increase in the messenger RNA and protein levels
      of SCG2 in granulosa cells collected early during the periovulatory period and
      just prior to ovulation (humans: 12 to 34 hours; monkeys: 12 to 36 hours;
      rodents: 4 to 12 hours post-hCG). This induction by hCG was recapitulated in an
      in vitro culture system utilizing granulosa-lutein cells from in vitro
      fertilization patients. Using this system, inhibition of downstream LH receptor
      signaling pathways revealed that the initial induction of SCG2 is regulated, in
      part, by epidermal growth factor receptor signaling. Further, human ovarian
      microvascular endothelial cells were treated with SN (1 to 100 ng/mL) and
      subjected to angiogenesis assays. SN significantly increased endothelial cell
      migration and new sprout formation, suggesting induction of ovarian angiogenesis.
      These results establish that SCG2 is increased in granulosa cells across species
      during the periovulatory period and that SN may mediate ovulatory angiogenesis in
      the human ovary. These findings provide insight into the regulation of human
      ovulation and fertility.

PMID- 29648637
TI  - Medium and long-term emergency department utilization after oesophagectomy: a
      population-based analysis.
AB  - OBJECTIVES: Oesophagectomy is a complex operation with the potential for
      prolonged recovery. The aim of this study was to evaluate healthcare resource
      utilization, specifically emergency department (ED) visits within 1 year of
      oesophagectomy, and to identify risk factors for ED visits and frequent ED use
      (FEDU). METHODS: A retrospective cohort study of consecutive oesophagectomies for
      cancer in all Ontario hospitals was conducted using linked health data (2000
      2012) including the ability to identify ED visits at non-index hospitals. Ontario
      has a single-payer healthcare system with a population of 13.8-million people.
      Multivariable regression was used to identify independent factors associated with
      ED visits and FEDU (>=3 ED visits) within 1 year after oesophagectomy. RESULTS:
      There were 3344 oesophagectomies with in-hospital mortality of 5.8% (n = 193). Of
      those discharged, 16.4% (n = 549), 36.0% (n = 1203) and 55.8% (n = 1866) had ED
      visits within 30 days, 90 days and 1 year, respectively. Higher comorbidity
      [adjusted odds ratio (aOR) = 1.08, 95% confidence interval (CI): 1.05-1.11, P <
      0.0001], rurality (aOR = 1.40, 95% CI: 1.10-1.78, P = 0.006) and receipt of
      chemotherapy and/or radiation therapy (aOR = 2.55, 95% CI: 2.12-3.08, P < 0.0001)
      were independent risk factors for ED visits within 1 year of oesophagectomy.
      Thoracoscopic-assisted surgery was independently associated with decreased ED
      visits (aOR = 0.67, 95% CI: 0.45-0.99, P = 0.049). Eight hundred and thirteen
      (24.3%) patients had FEDU. Higher comorbidity (aOR = 1.11, 95% CI: 1.08-1.14, P <
      0.0001), rurality (aOR = 1.66, 95% CI: 1.31-2.10, P < 0.0001) and receipt of
      chemotherapy and/or radiation therapy (aOR = 2.38, 95% CI: 1.93-2.93, P < 0.0001)
      were independent risk factors for FEDU. One health region had more ED visits (P =
      0.04) and more FEDU (P = 0.001) when compared with the other regions. There were
      higher ED visits and FEDU in the later years of the study period (both P <
      0.0001). CONCLUSIONS: ED visits are common after oesophagectomy with almost 25%
      of patients having >=3 visits and >50% having >=1 visit within 1 year of
      oesophagectomy. We have identified demographic, surgical and regional risk
      factors for the potential targeted quality improvement.

PMID- 29648640
TI  - Should extended blastocyst culture include Day 7?
AB  - Extended culture to the blastocyst stage is widely practised, improving embryo
      selection and promoting single embryo transfer. Selection of useable blastocysts
      typically occurs on Days 5 and 6 of embryo culture. Embryos not suitable for
      transfer, biopsy or cryopreservation after Day 6 are routinely discarded. Some
      embryos develop at a slower rate, however, forming blastocysts on Day 7 of
      culture. Day 7 blastocysts can be viable, they can be of top morphological grade,
      euploid and result in a healthy live birth. Since ending culture on Day 6 is
      current practice in most clinics, viable Day 7 blastocysts may be prematurely
      discarded. Although Day 7 blastocysts make up only 5% of useable blastocysts,
      those which are suitable for cryopreservation or biopsy are clinically
      significant. Overall, culturing embryos an additional day increases the number of
      useable embryos per IVF cycle and provides further opportunity for pregnancy for
      patients, especially those who have only a few or low-quality blastocysts.

PMID- 29648639
TI  - A natural non-Watson-Crick base pair in human mitochondrial tRNAThr causes
      structural and functional susceptibility to local mutations.
AB  - Six pathogenic mutations have been reported in human mitochondrial tRNAThr
      (hmtRNAThr); however, the pathogenic molecular mechanism remains unclear.
      Previously, we established an activity assay system for human mitochondrial
      threonyl-tRNA synthetase (hmThrRS). In the present study, we surveyed the
      structural and enzymatic effects of pathogenic mutations in hmtRNAThr and then
      focused on m.15915 G > A (G30A) and m.15923A > G (A38G). The harmful evolutionary
      gain of non-Watson-Crick base pair A29/C41 caused hmtRNAThr to be highly
      susceptible to mutations disrupting the G30-C40 base pair in various ways; for
      example, structural integrity maintenance, modification and aminoacylation of
      tRNAThr, and editing mischarged tRNAThr. A similar phenomenon was observed for
      hmtRNATrp with an A29/C41 non-Watson-Crick base pair, but not in bovine mtRNAThr
      with a natural G29-C41 base pair. The A38G mutation caused a severe reduction in
      Thr-acceptance and editing of hmThrRS. Importantly, A38 is a nucleotide
      determinant for the t6A modification at A37, which is essential for the coding
      properties of hmtRNAThr. In summary, our results revealed the crucial role of the
      G30-C40 base pair in maintaining the proper structure and function of hmtRNAThr
      because of A29/C41 non-Watson-Crick base pair and explained the molecular outcome
      of pathogenic G30A and A38G mutations.

PMID- 29648641
TI  - Factors associated with ever use of mammography in a limited resource setting. A
      mixed methods study.
AB  - Objective: To evaluate facilitators and barriers influencing mammography
      screening participation among women. Design: Mixed methods study. Setting: Three
      hospital catchment areas in Hidalgo, Mexico. Participants: Four hundred and fifty
      five women aged 40-69 years. Intervention: Three hundred and eighty women
      completed a survey about knowledge, beliefs and perceptions about breast cancer
      screening, and 75 women participated in semi-structured, in-person interviews.
      Survey data were analyzed using logistic regression; semi-structured interviews
      were transcribed and analyzed using elements of the grounded theory method. Main
      Outcome Measure: Women were categorized as never having had mammography or having
      had at least one mammogram in the past. Results: From survey data, having had a
      Pap in the past year was associated with ever having had breast screening (odds
      ratio = 2.15; 95% confidence interval 1.30-3.54). Compared with never-screened
      women, ever-screened women had better knowledge of Mexican recommendations for
      the frequency of mammography screening (49.5% vs 31.7% P < 0.001). A higher
      percentage of never-screened women perceived that a mammography was a painful
      procedure (44.5% vs 33.8%; P < 0.001) and feared receiving bad news (38.4% vs
      22.2%; P < 0.001) compared with ever-screened women. Women who participated in
      semi-structured, in-person interviews expressed a lack of knowledge about Mexican
      standard mammographic screening recommendations for age for starting mammography
      and its recommended frequency. Women insured under the 'Opportunities' health
      insurance program said that they are referred to receive Pap tests and
      mammography. Conclusions: Local strategies to reduce mammogram-related pain and
      fear of bad news should work in tandem with national programs to increase access
      to screening.

PMID- 29648642
TI  - A novel forehead temperature-regulating device for insomnia: a randomized
      clinical trial.
AB  - Study Objectives: Insomnia is one of the most common disorders in the general
      population. Hypnotic medications are efficacious, but their use is limited by
      adverse events (AEs). This study evaluated the safety and efficacy of a novel
      forehead temperature-regulating device that delivers frontal cerebral thermal
      therapy (maintained at 14-16 degrees C, equivalent to 57-61 degrees F) for the
      treatment of insomnia. Methods: This was a prospective, randomized controlled
      trial involving two nights of therapy in 106 adults diagnosed with insomnia. The
      main outcome measures included latency to persistent sleep and sleep efficiency
      derived from polysomnographic (PSG) recordings and frequency and severity of AEs.
      Results: The safety profile was comparable to sham treatment. Statistically
      significant differences were not found in the two a priori co-primary endpoint
      measures absolute latency to persistent sleep (p = 0.092) or absolute sleep
      efficiency. Frontal cerebral thermal therapy produced improvements over sham in
      other convergent measures of sleep latency including relative changes from
      baseline in latency to persistent sleep (p = 0.013), the latency to stage 1 NREM
      sleep (p = 0.006), the latency to stage 2 NREM sleep (p = 0.002), a trend for the
      latency to stage 3 NREM sleep (p = 0.055), and an increase in the minutes of
      sleep during the first hour of the night (p = 0.024). Conclusions: Two-night
      frontal cerebral thermal therapy produced improvements in PSG measures of
      insomnia patients' ability to fall asleep and had a benign safety profile.
      Further studies are warranted to determine the role of this therapy in the longer
      term management of insomnia. Trial Registration: clinicaltrials.gov Identifier:
      NCT01966211.

PMID- 29648644
TI  - Management of patients with coronary heart disease in family medicine: correlates
      of quality of care.
AB  - Objectives: Family medicine plays an important role in quality of care (QoC) of
      coronary heart disease (CHD) patients. This study's aim was to determine the
      quality of secondary cardiovascular disease prevention in the everyday practice
      of family physicians. Design: This study was observational cross-sectional.
      Setting: About 36 randomly selected family medicine practices stratified by size
      and location in Slovenia. Participants: CHD patients randomly selected from a
      patient register available in family medicine practices. Main Outcome Measure(s):
      The instrument for assessment of quality included a form for collecting data from
      medical records, a general practice assessment questionnaire and a patient
      questionnaire. QoC was defined by two composite variables, namely risk factor
      registration and CHD patient process of care, as the two care outcomes. In
      multivariate analysis, we performed multilevel regression analysis to identify
      the associations between QoC, the patient and the practice characteristics.
      Results: The final sample included 423 CHD patients from 36 family medicine
      practices. Risk factor registration was associated with the practice organisation
      score (P = 0.004), practice size (P = 0.042), presence of comorbid
      atherosclerotic diseases (P = 0.043) and a lower age of CHD patients (P = 0.001).
      CHD patient process of care was associated with the practice organisation score
      (0.045) and a lower age of CHD patients (P = 0.035). Conclusions: The most
      important factors affecting the quality of CHD patient care were linked to the
      organisational characteristics of the family medicine practices.

PMID- 29648643
TI  - Mutations in glycyl-tRNA synthetase impair mitochondrial metabolism in neurons.
AB  - The nuclear-encoded glycyl-tRNA synthetase gene (GARS) is essential for protein
      translation in both cytoplasm and mitochondria. In contrast, different genes
      encode the mitochondrial and cytosolic forms of most other tRNA synthetases.
      Dominant GARS mutations were described in inherited neuropathies, while recessive
      mutations cause severe childhood-onset disorders affecting skeletal muscle and
      heart. The downstream events explaining tissue-specific phenotype-genotype
      relations remained unclear. We investigated the mitochondrial function of GARS in
      human cell lines and in the GarsC210R mouse model. Human-induced neuronal
      progenitor cells (iNPCs) carrying dominant and recessive GARS mutations showed
      alterations of mitochondrial proteins, which were more prominent in iNPCs with
      dominant, neuropathy-causing mutations. Although comparative proteomic analysis
      of iNPCs showed significant changes in mitochondrial respiratory chain complex
      subunits, assembly genes, Krebs cycle enzymes and transport proteins in both
      recessive and dominant mutations, proteins involved in fatty acid oxidation were
      only altered by recessive mutations causing mitochondrial cardiomyopathy. In
      contrast, significant alterations of the vesicle-associated membrane protein
      associated protein B (VAPB) and its downstream pathways such as mitochondrial
      calcium uptake and autophagy were detected in dominant GARS mutations. The role
      of VAPB has been supported by similar results in the GarsC210R mice. Our data
      suggest that altered mitochondria-associated endoplasmic reticulum (ER) membranes
      (MAM) may be important disease mechanisms leading to neuropathy in this
      condition.

PMID- 29648646
TI  - Learning from errors for continuously improving patient safety.

PMID- 29648645
TI  - Does human endometrial LGR5 gene expression suggest the existence of another
      hormonally regulated epithelial stem cell niche?
AB  - STUDY QUESTION: Is human endometrial leucine-rich repeat-containing G-protein
      coupled receptor 5 (LGR5) gene expression limited to the postulated epithelial
      stem cell niche, stratum basalis glands, and is it hormonally regulated? SUMMARY
      ANSWER: LGR5 expressing cells are not limited to the postulated stem cell niche
      but LGR5 expression is hormonally regulated. WHAT IS KNOWN ALREADY: The human
      endometrium is a highly regenerative tissue; however, endometrial epithelial stem
      cell markers are yet to be confirmed. LGR5 is a marker of stem cells in various
      epithelia. STUDY DESIGN, SIZE, DURATION: The study was conducted at a University
      Research Institute. Endometrial samples from 50 healthy women undergoing benign
      gynaecological surgery with no endometrial pathology at the Liverpool Women's
      hospital were included and analysed in the following six sub-categories;
      proliferative, secretory phases of menstrual cycle, postmenopausal, those using
      oral and local progestagens and samples for in vitro explant culture.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: In this study, we used the gold
      standard method, in situ hybridisation (ISH) along with qPCR and a systems
      biology approach to study the location of LGR5 gene expression in full thickness
      human endometrium and Fallopian tubes. The progesterone regulation of endometrial
      LGR5 was examined in vivo and in short-term cultured endometrial tissue explants
      in vitro. LGR5 expression was correlated with epithelial proliferation (Ki67),
      and expression of previously reported epithelia progenitor markers (SOX9 and SSEA
      1) immunohistochemistry (IHC). MAIN RESULTS AND THE ROLE OF CHANCE: LGR5 gene
      expression was significantly higher in the endometrial luminal epithelium than in
      all other epithelial compartments in the healthy human endometrium, including the
      endometrial stratum basalis (P < 0.05). The strongest SSEA-1 and SOX9 staining
      was observed in the stratum basalis glands, but the general trend of SOX9 and
      SSEA-1 expression followed the same cyclical pattern of expression as LGR5.
      Stratum functionalis epithelial Ki67-LI and LGR5 expression levels correlated
      significantly (r = 0.74, P = 0.01), however, they did not correlate in luminal
      and stratum basalis epithelium (r = 0.5 and 0.13, respectively). Endometrial LGR5
      demonstrates a dynamic spatiotemporal expression pattern, suggesting hormonal
      regulation. Oral and local progestogens significantly reduced endometrial LGR5
      mRNA levels compared with women not on hormonal treatment (P < 0.01). Our data
      were in agreement with in silico analysis of published endometrial microarrays.
      LARGE SCALE DATA: We did not generate our own large scale data but interrogated
      publically available large scale data sets. LIMITATIONS, REASONS FOR CAUTION: In
      the absence of reliable antibodies for human LGR5 protein and validated lineage
      markers for the various epithelial populations that potentially exist within the
      endometrium, our study does not formally characterise or examine the functional
      ability of the resident LGR5+ cells as multipotent. WIDER IMPLICATIONS OF THE
      FINDINGS: These data will facilitate future lineage tracing studies in the human
      endometrial epithelium; to identify the location of stem cells and further
      complement the in vitro functional studies, to confirm if the LGR5 expressing
      epithelial cells indeed represent the epithelial stem cell population. STUDY
      FUNDING/COMPETING INTEREST(S): This work was supported by funding from the
      Wellbeing of Women project grant (RTF510) and Cancer Research UK (A14895). None
      of the authors have any conflicts of interest to disclose.

PMID- 29648647
TI  - A prospective study of physical activity and fecundability in women with a
      history of pregnancy loss.
AB  - STUDY QUESTION: Is physical activity (PA) associated with fecundability in women
      with a history of prior pregnancy loss? SUMMARY ANSWER: Higher fecundability was
      related to walking among overweight/obese women and to vigorous PA in women
      overall. WHAT IS KNOWN ALREADY: PA may influence fecundability through altered
      endocrine function. Studies evaluating this association have primarily utilized
      Internet-based recruitment and self-report for pregnancy assessment and have
      yielded conflicting results. STUDY DESIGN, SIZE, DURATION: This is a secondary
      analysis of the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial
      (2007-2011), a multisite, randomized controlled trial of preconception-initiated
      low-dose aspirin. PARTICIPANTS/MATERIALS, SETTING, METHODS: Healthy women (n =
      1214), aged 18-40 and with 1-2 prior pregnancy losses, were recruited from four
      US medical centers. Participants were followed for up to six menstrual cycles
      while attempting pregnancy and through pregnancy for those who became pregnant.
      Time to hCG detected pregnancy was assessed using discrete-time Cox proportional
      hazard models to estimate fecundability odds ratios (FOR) adjusted for
      covariates, accounting for left truncation and right censoring. MAIN RESULTS AND
      THE ROLE OF CHANCE: The association of walking with fecundability varied
      significantly by BMI (P-interaction = 0.01). Among overweight/obese women,
      walking >=10 min at a time was related to improved fecundability (FOR = 1.82, 95%
      CI: 1.19, 2.77). In adjusted models, women reporting >4 h/wk of vigorous activity
      had significantly higher fecundability (FOR = 1.69, 95% CI: 1.24, 2.31) compared
      to no vigorous activity. Associations of vigorous activity with fecundability
      were not significantly different by BMI (P-interaction = 0.9). Moderate activity,
      sitting, and International Physical Activity Questionnaire (IPAQ) categories were
      not associated with fecundability overall or in BMI-stratified analyses.
      LIMITATIONS, REASONS FOR CAUTION: Some misclassification of PA levels as
      determined by the short form of the IPAQ is likely to have occurred, and may have
      led to non-differential misclassification of exposure in our study. Information
      on diet and change in BMI was not collected and may have contributed to some
      residual confounding in our results. The generalizability of our results may be
      limited as our population consisted of women with a history of one or two
      pregnancy losses. WIDER IMPLICATIONS OF THE FINDINGS: These findings provide
      positive evidence for the benefits of PA in women attempting pregnancy,
      especially for walking among those with higher BMI. Further study is necessary to
      clarify possible mechanisms through which walking and vigorous activity might
      affect time-to-pregnancy. STUDY FUNDING/COMPETING INTEREST(S): This work was
      funded by the Intramural Research Program of the Eunice Kennedy Shriver National
      Institute of Child Health and Human Development. The authors report no conflicts
      of interest in this work. TRIAL REGISTRATION NUMBER: #NCT00467363.

PMID- 29648648
TI  - FGF signaling deregulation is associated with early developmental skeletal
      defects in animal models for mucopolysaccharidosis type II (MPSII).
AB  - Skeletal abnormalities represent a major clinical burden in patients affected by
      the lysosomal storage disorder mucopolysaccharidosis type II (MPSII, OMIM
      #309900). While extensive research has emphasized the detrimental role of stored
      glycosaminoglycans (GAGs) in the bone marrow (BM), a limited understanding of
      primary cellular mechanisms underlying bone defects in MPSII has hampered the
      development of bone-targeted therapeutic strategies beyond enzyme replacement
      therapy (ERT). We here investigated the involvement of key signaling pathways
      related to the loss of iduronate-2-sulfatase activity in two different MPSII
      animal models, D. rerio and M. musculus. We found that FGF pathway activity is
      impaired during early stages of bone development in IDS knockout mice and in a
      newly generated Ids mutant fish. In both models the FGF signaling deregulation
      anticipated a slow but progressive defect in bone differentiation, regardless of
      any extensive GAGs storage. We also show that MPSII patient fibroblasts harboring
      different mutations spanning the IDS gene exhibit perturbed FGF signaling-related
      markers expression. Our work opens a new venue to discover possible druggable
      novel key targets in MPSII.

PMID- 29648651
TI  - Is Lean sustainable in today's NHS hospitals? A systematic literature review
      using the meta-narrative and integrative methods.
AB  - Purpose: Methodological variance and quality, heterogeneity of value and
      divergent approaches are reasons for the varied results of Lean interventions in
      healthcare despite ongoing global popularity. However, there is piecemeal
      evidence addressing the sustainability of initiatives-the aim of this review is
      to use an integrative approach to consider Lean's sustainability and the quality
      of available evidence in today's National Health Service (NHS). Data sources: A
      literature review of AMED, CINAHL, Cochrane, JBI, SCOPUS, DelphiS, MEDLINE,
      EMBASE, MIDIRS, Web of Science and PsycINFO electronic databases was conducted.
      Study selection: Peer-reviewed studies in NHS hospitals/trusts that concerned
      undiluted, service-wide Lean adoption and contained quantitative data were
      included. Reference lists were consulted for evidence via a snowball approach.
      Methodological quality was assessed using an adapted critical appraisal tool.
      Data extraction: Research design, method of intervention, outcome measures and
      sustainability were extracted. Results of data synthesis: Electronic searches
      identified 12 studies eligible for inclusion. This comprised of five quasi
      experimental designs (one mixed-method), three multi-site analyses, one action
      research, one failure mode and effects analysis, one content analysis of annual
      reports and one systematic review. Six articles considered sustainability with
      two of these providing measured successes. Despite diverse and positive outcomes
      studies lacked scientific rigour, failed to consider confounding issues, were at
      risk of positive bias and did not demonstrate sustainability with any statistical
      significance. Conclusion: Lean has ostensible value but it is difficult to draw a
      conclusion on efficacy or sustainability. Higher quality scientific research into
      Lean and the effect of staffing cultures on initiatives are needed to ascertain
      the extent that Lean can affect healthcare quality and subsequently be sustained.

PMID- 29648650
TI  - NAFLD risk alleles in PNPLA3, TM6SF2, GCKR and LYPLAL1 show divergent metabolic
      effects.
AB  - Fatty liver has been associated with unfavourable metabolic changes in
      circulation. To provide insights in fatty liver-related metabolic deviations, we
      compared metabolic association profile of fatty liver versus metabolic
      association profiles of genotypes increasing the risk of non-alcoholic fatty
      liver disease (NAFLD). The cross-sectional associations of ultrasound-ascertained
      fatty liver with 123 metabolic measures were determined in 1810 (Nfatty liver =
      338) individuals aged 34-49 years from The Cardiovascular Risk in Young Finns
      Study. The association profiles of NAFLD-risk alleles in PNPLA3, TM6SF2, GCKR,
      and LYPLAL1 with the corresponding metabolic measures were obtained from a
      publicly available metabolomics GWAS including up to 24 925 Europeans. The risk
      alleles showed different metabolic effects: PNPLA3 rs738409-G, the strongest
      genetic NAFLD risk factor, did not associate with metabolic changes. Metabolic
      effects of GCKR rs1260326-T were comparable in many respects to the fatty liver
      associations. Metabolic effects of LYPLAL1 rs12137855-C were similar, but
      statistically less robust, to the effects of GCKR rs1260326-T. TM6SF2 rs58542926
      T displayed opposite metabolic effects when compared with the fatty liver
      associations. The metabolic effects of the risk alleles highlight heterogeneity
      of the molecular pathways leading to fatty liver and suggest that the fatty liver
      related changes in the circulating lipids and metabolites may vary depending on
      the underlying pathophysiological mechanism. Despite the robust cross-sectional
      associations on population level, the present results showing neutral or
      cardioprotective metabolic effects for some of the NAFLD risk alleles advocate
      that hepatic lipid accumulation by itself may not increase the level of
      circulating lipids or other metabolites.

PMID- 29648652
TI  - Arabidopsis Aspartic Protease ASPG1 Affects Seed Dormancy, Seed Longevity and
      Seed Germination.
AB  - Seed storage proteins (SSPs) provide free amino acids and energy for the process
      of seed germination. Although degradation of SSPs by the aspartic proteases
      isolated from seeds has been documented in vitro, there is still no genetic
      evidence for involvement of aspartic proteases in seed germination. Here we
      report that the aspartic protease ASPG1 (ASPARTIC PROTEASE IN GUARD CELL 1) plays
      an important role in the process of dormancy, viability and germination of
      Arabidopsis seeds. We show that aspg1-1 mutants have enhanced seed dormancy and
      reduced seed viability. A significant increase in expression of DELLA genes which
      act as repressors in the gibberellic acid signal transduction pathway were
      detected in aspg1-1 during seed germination. Seed germination of aspg1-1 mutants
      was more sensitive to treatment with paclobutrazol (PAC; a gibberellic acid
      biosynthesis inhibitor). In contrast, seed germination of ASPG1 overexpression
      (OE) transgenic lines showed resistant to PAC. The degradation of SSPs in
      germinating seeds was severely impaired in aspg1-1 mutants. Moreover, the
      development of aspg1-1 young seedlings was arrested when grown on the nutrient
      free medium. Thus ASPG1 is important for seed dormancy, seed longevity and seed
      germination, and its function is associated with degradation of SSPs and
      regulation of gibberellic acid signaling in Arabidopsis.

PMID- 29648654
TI  - Response to Jolobe: 'Medical abbreviations generate potentially dangerous
      ambiguity'.

PMID- 29648653
TI  - Neural substrates of social facilitation effects on incentive-based performance.
AB  - Throughout our lives we must perform tasks while being observed by others.
      Previous studies have shown that the presence of an audience can cause increases
      in an individual's performance as compared to when they are not being observed -
      a phenomenon called 'social facilitation'. However, the neural mechanisms
      underlying this effect, in the context of skilled-task performance for monetary
      incentives, are not well understood. We used functional magnetic resonance
      imaging (fMRI) to monitor brain activity while healthy human participants
      performed a skilled-task during conditions in which they were paid based on their
      performance and observed and not observed by an audience. We found that during
      social facilitation, social signals represented in the dorsomedial prefrontal
      cortex (dmPFC) enhanced reward value computations in ventromedial cortex (vmPFC).
      We also found that functional connectivity between dmPFC and ventral striatum
      (vSTR) was enhanced when participants exhibited social facilitation effects,
      indicative of a means by which social signals serve to modulate brain regions
      involved in regulating behavioral motivation. These findings illustrate how
      neural processing of social judgments gives rise to the enhanced motivational
      state that results in social facilitation of incentive-based performance.

PMID- 29648655
TI  - Cerebral cysticercosis.

PMID- 29648649
TI  - Infectious, inflammatory and 'autoimmune' male factor infertility: how do rodent
      models inform clinical practice?
AB  - BACKGROUND: Infection and inflammation of the reproductive tract are significant
      causes of male factor infertility. Ascending infections caused by sexually
      transmitted bacteria or urinary tract pathogens represent the most frequent
      aetiology of epididymo-orchitis, but viral, haematogenous dissemination is also a
      contributory factor. Limitations in adequate diagnosis and therapy reflect an
      obvious need for further understanding of human epididymal and testicular
      immunopathologies and their contribution to infertility. A major obstacle for
      advancing our knowledge is the limited access to suitable tissue samples.
      Similarly, the key events in the inflammatory or autoimmune pathologies affecting
      human male fertility are poorly amenable to close examination. Moreover, the
      disease processes generally have occurred long before the patient attends the
      clinic for fertility assessment. In this regard, data obtained from experimental
      animal models and respective comparative analyses have shown promise to overcome
      these restrictions in humans. OBJECTIVE AND RATIONALE: This narrative review will
      focus on male fertility disturbances caused by infection and inflammation, and
      the usefulness of the most frequently applied animal models to study these
      conditions. SEARCH METHODS: An extensive search in Medline database was performed
      without restrictions until January 2018 using the following search terms:
      'infection' and/or 'inflammation' and 'testis' and/or 'epididymis', 'infection'
      and/or 'inflammation' and 'male genital tract', 'male infertility', 'orchitis',
      'epididymitis', 'experimental autoimmune' and 'orchitis' or 'epididymitis' or
      'epididymo-orchitis', antisperm antibodies', 'vasectomy'. In addition to that,
      reference lists of primary and review articles were reviewed for additional
      publications independently by each author. Selected articles were verified by
      each two separate authors and discrepancies discussed within the team. OUTCOMES:
      There is clear evidence that models mimicking testicular and/or epididymal
      inflammation and infection have been instructive in a better understanding of the
      mechanisms of disease initiation and progression. In this regard, rodent models
      of acute bacterial epididymitis best reflect the clinical situation in terms of
      mimicking the infection pathway, pathogens selected and the damage, such as
      fibrotic transformation, observed. Similarly, animal models of acute testicular
      and epididymal inflammation using lipopolysaccharides show impairment of
      reproduction, endocrine function and histological tissue architecture, also seen
      in men. Autoimmune responses can be studied in models of experimental autoimmune
      orchitis (EAO) and vasectomy. In particular, the early stages of EAO development
      showing inflammatory responses in the form of peritubular lymphocytic
      infiltrates, thickening of the lamina propria of affected tubules, production of
      autoantibodies against testicular antigens or secretion of pro-inflammatory
      mediators, replicate observations in testicular sperm extraction samples of
      patients with 'mixed atrophy' of spermatogenesis. Vasectomy, in the form of sperm
      antibodies and chronic inflammation, can also be studied in animal models,
      providing valuable insights into the human response. WIDER IMPLICATIONS: This is
      the first comprehensive review of rodent models of both infectious and autoimmune
      disease of testis/epididymis, and their clinical implications, i.e. their
      importance in understanding male infertility related to infectious and non
      infectious/autoimmune disease of the reproductive organs.

PMID- 29648656
TI  - Pursuing origins of (poly)ethylene glycol-induced G-quadruplex structural
      modulations.
AB  - Molecular crowding conditions provided by high concentration of cosolutes are
      utilized for characterization of biomolecules in cell-mimicking environment and
      development of drug-delivery systems. In this context, (poly)ethylene glycols are
      often used for studying non-canonical DNA structures termed G-quadruplexes, which
      came into focus by emerging structural biology findings and new therapeutic drug
      design approaches. Recently, several reports were made arguing against using
      (poly)ethylene glycols in role of molecular crowding agents due to their direct
      impact on DNA G-quadruplex stability and topology. However, the available data on
      structural details underlying DNA interaction is very scarce and thus limits in
      depth comprehension. Herein, structural and thermodynamic analyses were
      strategically combined to assess G-quadruplex-cosolute interactions and address
      previously reported variances regarding the driving forces of G-rich DNA
      structural transformations under molecular crowding conditions. With the use of
      complementary (CD, NMR and UV) spectroscopic methods and model approach we
      characterized DNA G-quadruplex in the presence of the smallest and one of the
      largest typically used (poly)ethylene glycols. Dehydration effect is the key
      contributor to ethylene-glycol-induced increased stability of the G-quadruplex,
      which is in the case of the large cosolute mainly guided by the subtle direct
      interactions between PEG 8000 and the outer G-quartet regions.

PMID- 29648657
TI  - Influences of the Menstrual Phase on Cortisol Response to Stress in Nicotine
      Dependent Women: A Preliminary Examination.
AB  - Introduction: Evidence indicates that menstrual cycle phase plays a role in
      smoking withdrawal symptoms and craving. Stress increases these symptoms. Whether
      the stress regulatory mechanism is associated with menstrual phase and withdrawal
      symptoms is not well understood. Methods: Thirty-seven female smokers and 16
      female nonsmokers were asked to complete a laboratory session. In each group,
      approximately half of the participants were tested when they were in the
      follicular phase and the other half was tested in the luteal phase. The session
      included resting baseline, stress, and recovery periods. Saliva samples for the
      measurement of cortisol and subjective measures of craving and withdrawal
      symptoms were collected at the end of each period. Results: A series of repeated
      measures ANCOVAs found a significant smoking group x menstrual phase x sampling
      time interaction in cortisol levels (p < .05). Follow-up analyses indicated a
      reduced cortisol stress response in the luteal group relative to the follicular
      group in smokers (p < .02). This difference was not found in nonsmokers.
      Conclusions: Menstrual cycle phase is related to hormonal stress response and
      smoking withdrawal symptomatology. Implications: We show influences of the
      menstrual cycle phase on stress response among smokers. This is demonstrated by a
      reduced cortisol response to stress in the luteal group relative to the
      follicular group among smokers. This menstrual phase difference was not found in
      nonsmokers.

PMID- 29648659
TI  - Comment on "Trivalent CAR T cells overcome interpatient antigenic variability in
      glioblastoma".

PMID- 29648658
TI  - Pseudomonas aeruginosa partitioning protein ParB acts as a nucleoid-associated
      protein binding to multiple copies of a parS-related motif.
AB  - ParA and ParB homologs are involved in accurate chromosome segregation in
      bacteria. ParBs participate in the separation of ori domains by binding to parS
      palindromes, mainly localized close to oriC. In Pseudomonas aeruginosa neither
      ParB deficiency nor modification of all 10 parSs is lethal. However, such mutants
      show not only defects in chromosome segregation but also growth retardation and
      motility dysfunctions. Moreover, a lack of parB alters expression of over 1000
      genes, suggesting that ParB could interact with the chromosome outside its
      canonical parS targets. Here, we show that indeed ParB binds specifically to
      hundreds of sites in the genome. ChIP-seq analysis revealed 420 ParB-associated
      regions in wild-type strain and around 1000 in a ParB-overproducing strain and in
      various parS mutants. The vast majority of the ParB-enriched loci contained a
      heptanucleotide motif corresponding to one arm of the parS palindrome. All
      previously postulated parSs, except parS5, interacted with ParB in vivo. Whereas
      the ParB binding to the four parS sites closest to oriC, parS1-4, is involved in
      chromosome segregation, its genome-wide interactions with hundreds of parS half
      sites could affect chromosome topology, compaction and gene expression, thus
      allowing P. aeruginosa ParB to be classified as a nucleoid-associated protein.

PMID- 29648660
TI  - dUTPs conjugated with zwitterionic Cy3 or Cy5 fluorophore analogues are effective
      substrates for DNA amplification and labelling by Taq polymerase.
AB  - To develop structural modifications of dNTPs that are compatible with Taq DNA
      polymerase activity, we synthesized eight dUTP derivatives conjugated with Cy3 or
      Cy5 dye analogues that differed in charge and charge distribution throughout the
      fluorophore. These dUTP derivatives and commercial Cy3- and Cy5-dUTP were studied
      in Taq polymerase-dependent polymerase chain reactions (PCRs) and in primer
      extension reactions using model templates containing one, two and three adjacent
      adenine nucleotides. The relative amounts of amplified DNA and the kinetic
      parameters Km and Vmax characterizing the incorporation of labelled dUMPs have
      been estimated using fluorescence measurements and analysed. The dUTPs labelled
      with electroneutral zwitterionic analogues of Cy3 or Cy5 fluorophores were used
      by Taq polymerase approximately one order of magnitude more effectively than the
      dUTPs labelled with negatively charged analogues of Cy3 or Cy5. The nucleotidyl
      transferase activity of Taq polymerase was also observed and resulted in the
      addition of dUMPs labelled with electroneutral or positively charged fluorophores
      to the 3' ends of DNA. The introduction of mutually compensating charges into
      fluorophores or other functional groups conjugated to dNTPs can be considered a
      basis for the creation of PCR-compatible modified nucleoside triphosphates.

PMID- 29648661
TI  - Anticoagulation therapy in patients with non-valvular atrial fibrillation
      hospitalized in the Department of Medicine in the NOACs era.
AB  - Background: The treatment of atrial fibrillation (AF) includes anticoagulation
      (AC) therapy to prevent systemic emboli. Until recently, warfarin was the main AC
      agent, while in recent years, the new oral anticoagulants (NOACs) are
      increasingly being used. Aim: The aim of our study was to characterize the AC
      treatment policy of AF patients at the department of medicine in the NOACs era.
      Methods and Design: An observational study of consecutive hospitalized patients
      with non-valvular AF for a period of 3 months in Beilinson hospital (January to
      March 2017). Demographic characteristics, clinical data and AC therapeutic
      approach were compared to those from the pre-NOACs era, based on a previous
      study. Results: A total of 335 patients were hospitalized with either new (21%)
      or prior (79%) non-valvular AF. An increase in AC therapy among patients with
      prior and new AF was observed compared to the pre-NOACs era (76% vs. 59%; P <
      0.001 and 68% vs. 49%; P < 0.001, respectively). Totally, 76% of all patients
      were discharged with AC therapy compared to 55% in the pre-NOACs era. As in the
      pre-NOACs era, prior AC therapy was the main predictor for the prescription of AC
      therapy during hospitalization and discharge (OR = 13, 95% CI; 7-25, P = 0.0001).
      Conclusion: There is a significant increase in the AC therapy prescription,
      mainly NOACs, in hospitalized non-valvular AF patients. This increase could be
      explained by the difficulties in warfarin treatment and the benefits of NOACs.
      Nevertheless, a large observational study is required to prove these findings.

PMID- 29648662
TI  - Long-term causes of death in patients with infective endocarditis who undergo
      medical therapy only or surgical treatment: a nationwide population-based study.
AB  - OBJECTIVES: It is known that patients surviving infective endocarditis have a
      poor long-term prognosis; however, few studies have addressed the long-term
      causes of death in patients surviving the initial hospitalization. METHODS: Using
      Danish administrative registries, we identified patients admitted to a hospital
      with 1st time infective endocarditis in the period from January 1996 to December
      2014, who were alive at the time of discharge. The study population was
      categorized into (i) patients undergoing medical therapy only and (ii) patients
      undergoing surgical and medical treatment. We examined the cardiovascular and non
      cardiovascular causes of death. Using the Cox analysis, we investigated the
      associated risk of dying from a specific prespecified cause of death (heart
      failure, infective endocarditis and stroke) within the surgery group when
      compared with the medically treated group. RESULTS: We identified 5576 patients:
      4220 patients belonged to the medically treated group and 1356 patients to the
      surgery group. At the 10-year follow-up, the mortality rate was 63.1% and 41.6%
      in the medically treated group and the surgery group, respectively.
      Cardiovascular disease was the most frequent cause of death in both groups
      accounting for 52.5% in the medically treated group and 55.2% in the surgery
      group. Patients undergoing surgery were associated with a lower risk of dying
      from heart failure and stroke when compared with medically treated patients
      [hazard ratio = 0.66 (95% confidence interval: 0.46-0.94) and hazard ratio = 0.59
      (95% confidence interval: 0.37-0.96), respectively]. CONCLUSIONS: No major
      differences were found in the main causes of death between groups. Patients in
      the surgical group were associated with a lower risk of dying from heart failure
      and stroke when compared with medically treated patients.

PMID- 29648663
TI  - Incidence and Classification of Postcolonoscopy Colorectal Cancers in
      Inflammatory Bowel Disease: A Dutch Population-Based Cohort Study.
AB  - Background and Aims: Patients with inflammatory bowel disease [IBD] colitis are
      at increased risk for colorectal cancer [CRC]. We examined the proportion and
      most likely aetiology of potentially preventable postcolonoscopy CRCs [PCCRCs] in
      a population-based cohort. Furthermore, adherence to IBD surveillance guidelines
      was evaluated in both PCCRCs and the remainder of prevalent CRCs. Methods: All
      IBD patients diagnosed from 1991 to 2011 in the South Limburg region of The
      Netherlands [i.e. IBDSL cohort] were included. CRC cases were cross-checked with
      the Dutch pathology database and cancer registry. PCCRCs were defined as cancers
      diagnosed within 6-60 months after a colonoscopy and were classified as
      attributable to 'inappropriate surveillance interval', 'inadequate bowel
      examination', 'incomplete resection', 'missed lesion' or 'newly developed
      cancer'. Results: Twenty CRC cases were identified during 25,931 patient years of
      follow-up in 2,801 patients. The proportion of PCCRCs was 45.0%. Of these, 55.6%
      could be considered a 'missed lesion', while other possible aetiologies occurred
      only once. Considering both PCCRCs [n=9] and prevalent CRCs [n=11], ten were
      detected after publication of the surveillance guideline, but only three patients
      were enrolled. Moreover, 6 CRCs [30.0%] were detected before the recommended
      start of surveillance. Conclusions: In the IBDSL cohort, 45.0% of all CRCs were
      considered to be PCCRCs, mainly classified as missed lesions. Additionally, a
      large proportion of CRCs in our cohort were observed before a surveillance
      endoscopy was performed. Therefore, stringent adherence to IBD surveillance
      guidelines, improving endoscopy techniques and adjusting the surveillance program
      may lead to a decrease in CRC incidence.

PMID- 29648664
TI  - How does the association of general and central adiposity with glycaemia and
      blood pressure differ by gender and area of residence in a Malawian population: a
      cross-sectional study.
AB  - Background: In high-income settings, body mass index (BMI) and measures of
      central adiposity, such as waist-to-hip ratio (WHR) are associated with
      cardiometabolic risk, but evidence from low-income settings, particularly sub
      Saharan Africa (SSA), is limited. We assessed whether there are differences
      between central and general adiposity in their associations with fasting glucose,
      diabetes, systolic and diastolic blood pressures and hypertension, and whether
      these associations differ with gender or rural/urban setting in Malawi. Methods:
      We used data from a population-based study of 27 880 Malawian adults aged  >=18
      years, from both rural and urban areas. We used age-standardized z-scores of the
      means of BMI and WHR to directly compare their associations with glycaemic and
      blood pressure outcomes. Results: Mean fasting glucose and blood pressure values
      and odds of hypertension increased linearly across fifths of BMI and WHR, with
      stronger associations with BMI. For both BMI and WHR, the associations with
      outcomes were stronger in urban versus rural residents. The association with
      diabetes was stronger in women than men, whereas for blood-pressure related
      outcomes a stronger association was seen in men. Conclusions: BMI is more
      strongly associated with cardiometabolic risk in SSA, and might be a more useful
      measure than WHR, in this population. The greater positive association of
      adiposity with cardiometabolic outcomes in urban residents (where rates of
      overweight/obesity are already high) highlights the particular importance of
      addressing obesity within urban SSA populations.

PMID- 29648666
TI  - The Basic Helix-Loop-Helix Transcription Factor GubHLH3 Positively Regulates
      Soyasaponin Biosynthetic Genes in Glycyrrhiza uralensis.
AB  - Glycyrrhiza uralensis (licorice) is a widely used medicinal plant belonging to
      the Fabaceae. Its main active component, glycyrrhizin, is an oleanane-type
      triterpenoid saponin widely used as a medicine and as a natural sweetener.
      Licorice also produces other triterpenoids, including soyasaponins. Recent
      studies have revealed various oxidosqualene cyclases and cytochrome P450
      monooxygenases (P450s) required for the biosynthesis of triterpenoids in
      licorice. Of these enzymes, beta-amyrin synthase (bAS) and beta-amyrin C-24
      hydroxylase (CYP93E3) are involved in the biosynthesis of soyasapogenol B (an
      aglycone of soyasaponins) from 2,3-oxidosqualene. Although these biosynthetic
      enzyme genes are known to be temporally and spatially expressed in licorice, the
      regulatory mechanisms underlying their expression remain unknown. Here, we
      identified a basic helix-loop-helix (bHLH) transcription factor, GubHLH3, that
      positively regulates the expression of soyasaponin biosynthetic genes. GubHLH3
      preferentially activates transcription from promoters of CYP93E3 and CYP72A566,
      the second P450 gene newly identified and shown to be responsible for C-22beta
      hydroxylation in soyasapogenol B biosynthesis, in transient co-transfection
      assays of promoter-reporter constructs and transcription factors. Overexpression
      of GubHLH3 in transgenic hairy roots of G. uralensis enhanced the expression
      levels of bAS, CYP93E3 and CYP72A566. Moreover, soyasapogenol B and sophoradiol
      (22beta-hydroxy-beta-amyrin), an intermediate between beta-amyrin and
      soyasapogenol B, were increased in transgenic hairy root lines overexpressing
      GubHLH3. We found that soyasaponin biosynthetic genes and GubHLH3 were co
      ordinately up-regulated by methyl jasmonate (MeJA). These results suggest that
      GubHLH3 regulates MeJA-responsive expression of soyasaponin biosynthetic genes in
      G. uralensis. The regulatory mechanisms of triterpenoid biosynthesis in legumes
      are compared and discussed.

PMID- 29648665
TI  - Homozygous TAF8 mutation in a patient with intellectual disability results in
      undetectable TAF8 protein, but preserved RNA polymerase II transcription.
AB  - The human general transcription factor TFIID is composed of the TATA-binding
      protein (TBP) and 13 TBP-associated factors (TAFs). In eukaryotic cells, TFIID is
      thought to nucleate RNA polymerase II (Pol II) preinitiation complex formation on
      all protein coding gene promoters and thus, be crucial for Pol II transcription.
      In a child with intellectual disability, mild microcephaly, corpus callosum
      agenesis and poor growth, we identified a homozygous splice-site mutation in TAF8
      (NM_138572.2: c.781-1G > A). Our data indicate that the patient's mutation
      generates a frame shift and an unstable TAF8 mutant protein with an unrelated C
      terminus. The mutant TAF8 protein could not be detected in extracts from the
      patient's fibroblasts, indicating a loss of TAF8 function and that the mutation
      is most likely causative. Moreover, our immunoprecipitation and proteomic
      analyses show that in patient cells only partial TAF complexes exist and that the
      formation of the canonical TFIID is impaired. In contrast, loss of TAF8 in mouse
      embryonic stem cells and blastocysts leads to cell death and to a global decrease
      in Pol II transcription. Astonishingly however, in human TAF8 patient cells, we
      could not detect any cellular phenotype, significant changes in genome-wide Pol
      II occupancy and pre-mRNA transcription. Thus, the disorganization of the
      essential holo-TFIID complex did not affect global Pol II transcription in the
      patient's fibroblasts. Our observations further suggest that partial TAF
      complexes, and/or an altered TFIID containing a mutated TAF8, could support human
      development and thus, the absence of holo-TFIID is less deleterious for
      transcription than originally predicted.

PMID- 29648667
TI  - Epidemiology, risk factors and characteristics of pediatric stroke: a nationwide
      population-based study.
AB  - Background: Stroke, classically characterized as an acute acquired neurological
      deficit, is an important leading cause of death and chronic morbidity in
      children. Aims: This study reported the period prevalence, incidence and risk
      factors of pediatric stroke in Taiwan. Methods and procedures: All Taiwan
      inhabitants aged 1 month to 18 years registered in the National Health Insurance
      Research Database between 2010 and 2011 were enrolled in this study. Factors
      including age, sex, location and household income levels were collected.
      Incidence, period prevalence, mortality rate and the possible risks were
      completely evaluated. Outcomes and results: Hemorrhagic stroke has a
      significantly higher mortality rate than ischemic stroke (27.6% vs. 10.2%,
      P<0.05). Risk factors or underlying diseases for stroke were identified in 77.8%
      of the patients and 16.2% had more than one risk factor. The most common risk
      factors were vascular diseases (26.3%), infection (14.0%) and cardiac disorders
      (9.1%). Conclusions and implications: Infants younger than 2 years, boys and
      children in lower socioeconomic status have a significantly higher risk of
      stroke. Hemorrhagic stroke has a significantly higher mortality rate than
      ischemic stroke. More than half of the children with stroke had underlying
      diseases and the causes of hemorrhagic stroke are significantly different from
      ischemic stroke.

PMID- 29648669
TI  - A Clinical Prediction Model for Surgical Site Infections in Dermatological
      Surgery.
AB  - To adequately identify patients at risk for surgical site infection in
      dermatological surgery and effectively prescribe antibiotic prophylaxis, a
      prediction model may be helpful. Such a model was developed using data from 1,407
      patients who underwent dermatological surgery without antibiotic prophylaxis. The
      multivariable logistic regression model included type of closure, tumour location
      and defect size as risk factors. Bootstrapping was used for internal validation.
      The overall performance of the model was good, with an area under the curve of
      84.1%. The decision curve analysis showed that the model is potentially useful if
      one is willing to treat more than 8 patients with antibiotic prophylaxis to avoid
      one infection. For those who prefer more restrictive use of antibiotic
      prophylaxis, a default strategy of treating no patients at all with prophylaxis
      would be the best choice. External validation of the model is required before it
      can be widely applied.

PMID- 29648668
TI  - Widespread enhancer activation via ERalpha mediates estrogen response in vivo
      during uterine development.
AB  - Little is known regarding how steroid hormone exposures impact the epigenetic
      landscape in a living organism. Here, we took a global approach to understanding
      how exposure to the estrogenic chemical, diethylstilbestrol (DES), affects the
      neonatal mouse uterine epigenome. Integration of RNA- and ChIP-sequencing data
      demonstrated that ~80% of DES-altered genes had higher H3K4me1/H3K27ac signal in
      close proximity. Active enhancers, of which ~3% were super-enhancers, had a high
      density of estrogen receptor alpha (ERalpha) binding sites and were correlated
      with alterations in nearby gene expression. Conditional uterine deletion of
      ERalpha, but not the pioneer transcription factors FOXA2 or FOXO1, prevented the
      majority of DES-mediated changes in gene expression and H3K27ac signal at target
      enhancers. An ERalpha dependent super-enhancer was located at the Padi gene locus
      and a topological connection to the Padi1 TSS was documented using 3C-PCR.
      Chromosome looping at this site was independent of ERalpha and DES exposure,
      indicating that the interaction is established prior to ligand signaling.
      However, enrichment of H3K27ac and transcriptional activation at this locus was
      both DES and ERalpha-dependent. These data suggest that DES alters uterine
      development and consequently adult reproductive function by modifying the
      enhancer landscape at ERalpha binding sites near estrogen-regulated genes.

PMID- 29648671
TI  - Effect of Age on Melanoma Risk, Prognosis and Treatment Response.
AB  - As for all types of cancer, the incidence of melanoma increases with age.
      However, naevus counts (the principal risk factor for melanoma) decrease with
      age; hence the relationship between ageing and melanoma is complex. Subjects who
      maintain a high naevus count after the age of 50 years are more likely to be
      affected by melanoma, as their lesions do not senesce. Longer telomere length,
      which is strongly related to age, is linked to high naevus counts/melanoma risk;
      thus melanoma biology is influenced by factors that slow down ageing. Age is also
      an important prognostic factor in melanoma. Increasing age leads to worse
      survival in stages I, II and III. Sentinel lymph node (SLN) status, which is a
      strong predictor of melanoma survival, is also affected by age, as SLN positivity
      decreases with age. However, the prognostic value of SLN on survival increases
      with age, so, again, these relationships are complex. In patients with stage IV
      melanoma, age impacts on survival because it affects responses to treatment. This
      review examines the effects of age on melanoma risk, prognostic factors and
      responses to treatment.

PMID- 29648670
TI  - Lower-limb Ulcers in Systemic Sclerosis: A Multicentre Retrospective Case-control
      Study.
AB  - Lower-limb ulcers in systemic sclerosis patients are rarely reported. The aim of
      this study was to describe the main causes and outcomes of lower-limb ulcers in
      systemic sclerosis patients and to assess factors associated with ischaemic
      causes (arterial disease and/or microvascular impairment). A retrospective,
      multicentre, case-control study was conducted in 2013 and 2014, including 45
      systemic sclerosis patients presenting lower-limb ulcers between 2008 and 2013.
      The estimated prevalence of lower-limb ulcers among systemic sclerosis patients
      was 12.8%. Ulcers were related to venous insufficiency in 22 cases (49%),
      ischaemic causes in 21 (47%) and other causes in 2 (4%). Complete healing was
      observed in 60% of cases in a mean time of 10.3 months; 59% relapsed during a
      mean follow-up of 22 months. Ischaemic lower-limb ulcer outcomes were poor, with
      a 28.6% amputation rate. Logistic-regression multivariate analyses between
      ischaemic lower-limb ulcer cases and matched systemic sclerosis-controls
      identified past or concomitant digital ulcer and cutaneous sclerosis of the feet
      as independent risk factors associated with ischaemic lower-limb ulcers.

PMID- 29648672
TI  - Auditory System Involvement in Psoriasis.
AB  - Psoriasis is a systemic inflammatory disorder associated with many other chronic
      and progressive diseases. There are few studies on the association of psoriasis
      with alterations in auditory function. A clinical and instrumental pilot study of
      auditory function was performed with 77 psoriatic patients and 77 age- and sex
      matched healthy controls. The main results were: (i) hearing loss, mostly of
      sensorineural type, was significantly more frequent in patients than in controls;
      (ii) conductive and mixed hearing loss were more frequent in arthropathic than in
      non-arthropathic psoriatic patients; (iii) duration of psoriasis > 10 years or
      smoking were associated with higher frequency of hearing loss; (iv) psoriasis was
      more severe in patients with hearing loss than in those without hearing loss.
      Tympanogram abnormalities were found in patients more often than in controls.
      These data expand the list of extracutaneous conditions associated with
      psoriasis, and support the need for further basic and clinical research in this
      field.

PMID- 29648673
TI  - Structured Diagnostic Approach and Risk Assessment in Mucous Membrane Pemphigoid
      with Oesophageal Involvement.
AB  - Oesophageal involvement in mucous membrane pemphigoid is considered rare, but it
      may be underdiagnosed. To assess the incidence of oesophageal involvement in a
      group of patients with newly diagnosed mucous membrane pemphigoid we
      retrospectively analysed the medical records of 30 consecutive patients with
      mucous membrane pemphigoid diagnosed between 2006 and 2016 at the Department of
      Dermatology, University Hospital Wurzburg. Twenty-one patients (70%) reported
      symptoms indicative of oesophageal mucous membrane pemphigoid. Twelve patients
      (40%) underwent oesophagogastroduodenoscopy, and oesophageal pathology compatible
      with mucous membrane pemphigoid was endoscopically found in 9 cases (30%). In all
      patients indirect and direct immunofluorescence were performed. Patients with and
      without oesophageal involvement did not differ with regard to the results of
      indirect immunofluorescence on salt-split human skin and monkey oesophagus. Study
      results demonstrate the necessity of a standardized diagnostic work-up, including
      adequate tissue samples for direct immunofluorescence, to prevent underdiagnosis
      of oesophageal mucous membrane pemphigoid.

PMID- 29648674
TI  - Patient Burden is Associated with Alterations in Quality of Life in Adult
      Patients with Atopic Dermatitis: Results from the ECLA Study.

PMID- 29648675
TI  - Clinical Features of Chronic Spontaneous Urticaria that Predict Disease Prognosis
      and Refractoriness to Standard Treatment.
AB  - Chronic spontaneous urticaria (CSU) is characterized by heterogeneous activity,
      evolution, associated comorbidities and response to treatment. The aim of this
      study was to identify prognostic factors in patients with CSU that predict
      disease course and response to standard treatments. An observational
      retrospective study was conducted in a cohort of 549 patients with CSU, comparing
      patients with isolated CSU and those with CSU with concomitant inducible
      urticaria (CSU-CIndU). The factors associated with a worse prognosis in terms of
      duration and/or CSU activity and its episodes were: multiple episodes of CSU
      (19.2% had more than one lifetime episode of CSU), late-onset (63.6% of patients
      developed first onset of CSU after the age of 45 years), concomitant CIndU
      (20.2%) and functional serum autoreactivity. Patients with CSU-CIndU required
      more frequent therapy after 5 years and higher doses of 2nd-generation H1
      antihistamines. Of patients with a baseline Urticaria Activity Score 7 (UAS7)
      between 16 and 42, 84.6% required cyclosporine or omalizumab to achieve symptom
      control, compared with 15.4% of patients with a baseline UAS7 between 0 and 15
      (p?=?0.0013). Baseline CSU activity is the only factor found to be predictive for
      refractoriness to treatment with H1-antihistamines.

PMID- 29648677
TI  - Excess Productivity Costs of Systemic Lupus Erythematosus, Systemic Sclerosis,
      and Sjogren's Syndrome: A General Population-Based Study.
AB  - OBJECTIVE: Determine excess productivity losses and costs of systemic lupus
      erythematosus (SLE), systemic sclerosis (SSc), and Sjogren's syndrome (SjS) at
      the population level. METHODS: Administrative databases from the province of
      British Columbia, Canada, were used to establish population-based cohorts of SLE,
      SSc, and SjS, and matched comparison cohorts selected from the general
      population. Random samples from these cohorts were surveyed about time absent
      from paid and unpaid work, and working at reduced levels/efficiency
      (presenteeism), using validated labour questionnaires. We estimated excess
      productivity losses and costs of each diagnosis (over-and-above non-SARDs), using
      two-part models, and work disability rates (not-employed, due to health).
      RESULTS: Surveys were completed by 167 SLE, 42 SSc, 90 SjS, and 375 non-SARDs
      (comparison group). Altogether, predicted excess hours of paid and unpaid work
      loss were 3.5, 3.2, and 3.4 per-week for SLE, SSc, and SjS, respectively; excess
      costs of $86, $69, and $84 (2015 Canadian) per-week, or $4,494, $3,582, and
      $4,357 per-person annually. Costs for productivity losses from paid work stemmed
      mainly from presenteeism (SLE=69% of costs, SSc=67%, SjS=64%, non-SARDs=53%), not
      absenteeism. However, many working-age patients were not-employed at all, due to
      health (SLE=36%, SSc=32%, SjS=30%, non-SARDs=18%), and majority of total
      productivity costs were from unpaid work loss (SLE=73% of costs, SSc=74%,
      SjS=60%, non-SARDs=47%). Adjusted excess costs from these unpaid production
      losses were $127, $100, and $82 per-week, respectively, among SLE, SSc, and SjS.
      CONCLUSION: In this population-based sample of prevalent SLE, SSc, and SjS, lost
      productivity costs were substantial, mainly from presenteeism and unpaid work
      impairments. This article is protected by copyright. All rights reserved.

PMID- 29648676
TI  - Sentinel Lymph Node Biopsy in Cutaneous Squamous Cell Carcinoma Series of 37
      Cases and Systematic Review of the Literature.
AB  - Cutaneous squamous cell carcinoma (cSSC) is one of the most common skin cancers
      and can lead to patient death. Early detection of node metastasis is a major goal
      for dermatologists and oncologists. The procedure sentinel lymph node biopsy has
      been proposed to improve early detection of node metastasis. The aim of this
      study was to evaluate the efficacy and impact of this technique on the prognosis
      of cSSC. A total of 37 patients (Saint Louis Hospital, Paris, France) who had
      undergone sentinel lymph node biopsy and 290 cases from the literature were
      analysed. The mean rate of positive sentinel lymph node biopsy was 0.14 [95% CI
      0.09-0.22]. However, relapse-free survival and overall survival were not affected
      by sentinel lymph node status (log-rank test; p = 0.08 and p = 0.31,
      respectively), suggesting that this procedure is not mandatory in the management
      of cSSC.

PMID- 29648678
TI  - A shortage of cadavers: The predicament of regional anatomy education in mainland
      China.
AB  - Both in mainland China and around the world, regional anatomy stands as one of
      the most important basic science courses in medical school curricula. As such,
      dissection of human cadavers and use of prosected specimens remains the most
      essential teaching method in anatomy education. However, medical educators have
      raised increasing concerns about an ongoing shortage of cadavers for medical use
      in mainland China, a problem which may seriously limit the future development of
      human anatomy education. Based on a survey on cadaver usage in anatomy education
      in mainland China, this study found that the cadaver resources of most given
      medical schools in mainland China are associated with their geographic location,
      academic ranking, and local support for body donation policies. Effective
      measures to alleviate this shortage of cadavers may include future efforts to
      promote national-level body donation legislation, broader acceptance of body
      donation among Chinese citizens, and an efficient and humane protocol for body
      donation. Anat Sci Educ 11: 397-402. (c) 2018 American Association of Anatomists.

PMID- 29648679
TI  - The effect of content delivery style on student performance in anatomy.
AB  - The development of new technologies and ensuing pedagogical research has led many
      tertiary institutions to integrate and adopt online learning strategies. The
      authors of this study have incorporated online learning strategies into existing
      educational practices of a second year anatomy course, resulting in half of the
      course content delivered via face-to-face lectures, and half delivered online via
      tailored video vignettes, with accompanying worksheets and activities. The effect
      of the content delivery mode on student learning was analyzed by tailoring
      questions to content presented either face-to-face or online. Four practical
      tests were conducted across the semester with each consisting of four questions.
      Within each test, two questions were based on content delivered face-to-face, and
      two questions were based on content delivered online. Examination multiple choice
      questions were similarly divided and assessed. Findings indicate that student
      learning is consistent regardless of the mode of content delivery. However,
      student viewing habits had a significant impact on learning, with students who
      viewed videos multiple times achieving higher marks than those less engaged with
      the online content. Student comments also indicated that content delivery mode
      was not an influence on learning. Therefore student engagement, rather than the
      mode of content delivery, is a determinant of student learning and performance in
      human anatomy. Anat Sci Educ. (c) 2018 American Association of Anatomists.

PMID- 29648681
TI  - OMIP-045: Characterizing human head and neck tumors and cancer cell lines with
      mass cytometry.

PMID- 29648680
TI  - Review: What Is the Current Evidence for Disease Subsets in Giant Cell Arteritis?
AB  - Giant cell arteritis (GCA) is an autoimmune vasculitis affecting large and medium
      sized arteries. Ample evidence indicates that GCA is a heterogeneous disease in
      terms of symptoms, immune pathology, and response to treatment. In the current
      review, we discuss the evidence for disease subsets in GCA. We describe clinical
      and immunologic characteristics that may impact the risk of cranial ischemic
      symptoms, relapse rates, and long-term glucocorticoid requirements in patients
      with GCA. In addition, we discuss both proven and putative immunologic targets
      for therapy in patients with GCA who have an unfavorable prognosis. Finally, we
      provide recommendations for further research on disease subsets in GCA.

PMID- 29648682
TI  - Elderly-Onset Varicella Pneumonia in a Patient With Rheumatoid Arthritis Treated
      With Tofacitinib.

PMID- 29648683
TI  - Long-Term Outcomes Following Achievement of Clinically Inactive Disease in
      Juvenile Idiopathic Arthritis: The Importance of Definition.
AB  - OBJECTIVE: Potential targets for treat-to-target strategies in juvenile
      idiopathic arthritis are minimal disease activity (MDA) and clinically inactive
      disease (CID). We undertook this study to compare short- and long-term outcomes
      following achievement of MDA and CID on the 10-joint clinical Juvenile Arthritis
      Disease Activity Score (cJADAS10) and following achievement of CID on Wallace et
      al's preliminary criteria. METHODS: Children recruited to the Childhood Arthritis
      Prospective Study, a UK multicenter inception cohort, were selected if they were
      recruited prior to January 2011 and diagnosed as having oligoarthritis or
      rheumatoid factor-negative or -positive polyarthritis. One year following
      diagnosis, children were assessed for MDA on the cJADAS10 and for CID on both
      Wallace et al's preliminary criteria and the cJADAS10. Associations were tested
      between those disease states and functional ability, absence of joints with
      limited range of motion, psychosocial health, and pain at 1 year and annually to
      5 years. RESULTS: Of 832 children, 70% were female and the majority had
      oligoarthritis (68%). At 1 year, 21% had achieved CID according to both
      definitions, 7% according to Wallace et al's preliminary criteria alone, and 16%
      according to the cJADAS10 alone; 56% had not achieved CID. Only 10% of children
      in the entire cohort achieved MDA without also achieving CID. Achieving either
      early CID state was associated with a greater absence of joints with limited
      range of motion. However, only CID according to the cJADAS10 was associated with
      improved functional ability and psychosocial health. Achieving CID was superior
      to achieving MDA in terms of short- and long-term pain and the absence of joints
      with limited range of motion. CONCLUSION: CID on the cJADAS10 may be preferable
      as a treatment target to CID on Wallace et al's preliminary criteria in terms of
      both feasibility of application and long-term outcomes.

PMID- 29648684
TI  - Inhibitory Receptor Expression on T Cells as a Marker of Disease Activity and
      Target to Regulate Effector Cellular Responses in Rheumatoid Arthritis.
AB  - OBJECTIVE: Inhibitory receptors are essential for the regulation of effector
      immune responses and may play critical roles in autoimmune diseases. We evaluated
      whether inhibitory receptor expression on T cells from patients with rheumatoid
      arthritis (RA) were correlated with immune activation, disease activity, and
      response to treatment, as well as whether inhibitory receptor-mediated pathways
      were functional. METHODS: Using flow cytometry, we performed extensive phenotypic
      and functional evaluation of CD4+ and CD8+ T cells from the blood and synovial
      fluid (SF) of RA patients ex vivo and after culture. The relationship of each
      parameter with the Disease Activity Score in 28 joints using the erythrocyte
      sedimentation rate (DAS28-ESR) and response to treatment was examined. RESULTS:
      In RA patients with low levels of T cell activation, inhibitory receptor
      expression showed an inverse relationship with the DAS28-ESR. The frequency of T
      cells expressing multiple inhibitory receptors was reduced in untreated RA
      patients but returned to normal levels in treated patients. RA patients who
      responded to treatment showed an augmented frequency of inhibitory receptor
      expressing T cells that correlated with reduced inflammatory cytokine production
      in comparison to nonresponders. Higher frequencies of effector and memory T cells
      that expressed multiple inhibitory receptors were seen in SF than in peripheral
      blood. Notably, inhibitory pathways were operative in blood and synovial T cells
      from all RA patients, although cells from nonresponder patients were less
      sensitive to inhibition. CONCLUSION: Inhibitory receptor expression on T cells
      from RA patients is inversely correlated with effector T cell function and
      disease activity and may predict response to treatment. Furthermore, different
      inhibitory pathways are functional and cooperatively suppress synovial T cells,
      providing a rationale for new treatment strategies to regulate acute local
      inflammation.

PMID- 29648685
TI  - Association of physical examination knee effusion with bone marrow lesions: cross
      sectional and longitudinal analyses of a population-based cohort.
AB  - OBJECTIVE: To determine the association of physical examination (PE) effusion
      with prevalence of bone marrow lesions (BML) on MRI, and incidence/progression of
      BML over 3 years in knee osteoarthritis (OA). METHODS: A population-based cohort
      with knee pain (N=255) was assessed for PE effusion. On MRI, BML was graded 0-3
      (none, mild, moderate, severe), incidence/progression defined as a worsening in
      the sum of BML scores over six surfaces by >=1 grade. We analyzed the full cohort
      and mild disease subsample with Kellgren-Lawrence (KL) grade <3. Cross-sectional
      logistic and longitudinal exponential regression analyses were performed,
      adjusted for age, sex, BMI and pain. We calculated sensitivity, specificity,
      positive predictive value (PPV) and negative predictive value (NPV) for PE
      effusion vs. BML (prevalence and incidence/progression). RESULTS: Weighted mean
      age was 56.7 years, mean BMI 26.5, 56.3% were female, 20.1% had PE effusion and
      80.7% had KL<3. PE effusion was significantly associated with prevalent BML in
      the full cohort (OR 6.10; 95% CI 2.77, 13.44) and KL<3 cohort (OR 6.88, 95% CI
      2.76, 17.15). Sensitivity/specificity/PPV/NPV were respectively
      34.6/92.5/79.9/62.1% and 31.7/94.0/75.5/70.1%. Longitudinally, PE effusion was
      not significantly associated with BML incidence/progression in the full cohort
      (HR 1.83, 95% CI 0.95, 3.52) or KL<3 cohort (HR 1.73, 95% CI 0.69, 4.33).
      Sensitivity/specificity/PPV/NPV were respectively 32.0/82.2/42.2/74.9% and
      21.2/85.6/30.1/78.8%. CONCLUSION: BMLs on MRI can be predicted from PE effusion
      cross-sectionally with high PPV of 79.9%. Assessment for knee effusion on
      physical examination is useful for determining potential candidates with BML
      before costly MRI screening for recruitment into clinical trials. This article is
      protected by copyright. All rights reserved.

PMID- 29648686
TI  - Development and Validation of a Novel Evidence-Based Lupus Multivariable Outcome
      Score for Clinical Trials.
AB  - OBJECTIVE: Trials of new systemic lupus erythematosus (SLE) treatments are
      hampered by the lack of effective outcome measures. To address this, we developed
      a novel Lupus Multivariable Outcome Score (LuMOS) and assessed its performance
      using data from 2 randomized controlled trials of belimumab in patients with SLE.
      METHODS: The LuMOS formula was developed by analyzing raw data from 2 pivotal
      trials, the Study of Belimumab in Subjects with SLE 52-week (BLISS-52) and 76
      week (BLISS-76) trials, which are the basis for approval of belimumab. Using the
      BLISS-76 trial data as the learning data set, we carried out multivariable
      logistic regression analyses to optimize discrimination of outcomes between
      patients treated with 10 mg/kg belimumab and patients receiving placebo over the
      first 52 weeks of follow-up. In addition, the performance of LuMOS was assessed
      using an independent validation data set from the BLISS-52 trial. RESULTS: The
      LuMOS model incorporated the following response criteria: a >=4-point reduction
      on the Safety of Estrogens in Lupus Erythematosus National Assessment version of
      the SLE Disease Activity Index, an increase in C4 levels, a decrease in anti
      double-stranded DNA titers, and changes in the British Isles Lupus Assessment
      Group scores for organ system manifestations (no worsening in renal components,
      and improvements in mucocutaneous components). A decrease in the prednisone dose
      and increase in C3 levels had very minor impacts on the total LuMOS score. In all
      analyses of the BLISS-76 and BLISS-52 trial data sets, the mean LuMOS scores were
      significantly higher (P < 0.0001) in patients treated with 1 mg or 10 mg
      belimumab compared to placebo. In contrast to the performance of the SLE
      Responder Index 4 (SRI-4), the LuMOS revealed significant differences between the
      active treatment group (1 mg belimumab in the BLISS-76 cohort) and placebo group.
      The effect sizes were significantly much higher with the LuMOS than with the SRI
      4. CONCLUSION: The evidenced-based LuMOS outcome scoring system, developed with
      data from the BLISS-76 trial of belimumab in patients with SLE and validated with
      data from the BLISS-52 trial, exhibits a superior capacity to discriminate
      responders from nonresponders when compared to the SRI-4. Use of the LuMOS may
      improve the efficiency and power of analyses in future lupus trials.

PMID- 29648687
TI  - Lipid Testing and Statin Prescription among Medicaid Recipients with Systemic
      Lupus Erythematosus, Diabetes Mellitus and the General Medicaid Population.
AB  - OBJECTIVE: Cardiovascular disease (CVD) risks among patients with systemic lupus
      erythematosus (SLE) are similar to those in diabetes mellitus (DM). We
      investigated whether patients with SLE receive lipid testing and statin
      prescriptions comparably to DM patients and to individuals without either
      disease. METHODS: We identified U.S. Medicaid beneficiaries ages 18-65, residing
      in 29 states from 2007-2010 with prevalent SLE. Each SLE patient was age- and sex
      matched to two DM, and four general Medicaid recipients without either disease.
      We compared the proportions of patients in each cohort who received > 1 lipid
      test and > 1 statin prescription during one-year follow-up. We used multivariable
      logistic regression to calculate the odds of lipid testing and statin
      prescription and conditional logistic regression to compare matched cohorts.
      RESULTS: We identified three Medicaid patient cohorts: 25,950 SLE; 51,900 DM; and
      103,800 with neither condition. In these cohorts, lipid testing was performed in
      24% of SLE, 43% of DM and 16% with neither, and statin prescriptions were
      dispensed in 11%, 33% and 7%. SLE patients were 66% less likely (OR 0.34, 95% CI
      0.34-0.35) to have lipids tested and 82% less likely (OR 0.18, 95% CI 0.18-0.18)
      to fill a statin prescription than DM patients. They were also less likely (OR
      0.89, 95% CI 0.84-0.94) to fill a statin prescription than general Medicaid
      patients. CONCLUSIONS: Despite elevated CVD risk, SLE patients receive less lipid
      testing and statin prescriptions than age- and sex-matched DM and general
      Medicaid patients and this gap should be a target for improvement. This article
      is protected by copyright. All rights reserved.

PMID- 29648688
TI  - Quantitative signal intensity alteration in infrapatellar fat pad predict
      incident radiographic osteoarthritis: the Osteoarthritis Initiative.
AB  - OBJECTIVES: To determine if infrapatellar fat pad (IPFP) signal intensity (SI)
      measures are predictive of incident radiographic osteoarthritis (iROA) over 4
      years in the OA Initiative (OAI) study. METHODS: Case knees (n=355) defined by
      iROA were matched one-to-one by gender, age and radiographic status with control
      knees. T2-weighted MR images were assessed at P0 (the visit when iROA was found
      on radiograph), P-1 (1 year prior to P0) and baseline, and utilized to assess
      IPFP SI semi-automatically using MATLAB. Conditional logistic regression analyses
      were used to assess risk of iROA associated with IPFP SI alteration after
      adjustment for covariates. RESULTS: Participants were on average 60.2 years old,
      predominantly female (66.7%) and overweight (mean BMI: 28.3). Baseline IPFP
      measures including mean value and standard deviation of IPFP SI [Mean(IPFP),
      sDev(IPFP)] (HR, 95%CI: 5.2, 1.1 to 23.6 and 5.7, 2.2 to 14.5, respectively),
      mean value and standard deviation of IPFP high SI [Mean(H), sDev(H)] (HR, 95%CI:
      3.3, 1.7 to 6.4 and 3.1, 1.3 to 7.7, respectively), median value and upper
      quartile value of IPFP high SI [Median(H), UQ(H)], and clustering effect of high
      SI [Clustering factor(H)] were associated with iROA during 4 years. All P-1 IPFP
      measures were associated with iROA after 12 months. P-0 IPFP SI measures were all
      associated with ROA. CONCLUSIONS: The quantitative segmentation of high signal in
      IPFP is confirming previous work based on semiquantitative assessment suggesting
      its predictive validity. The IPFP high SI alteration could be an important
      imaging biomarker to predict the occurrence of radiographic OA. This article is
      protected by copyright. All rights reserved.

PMID- 29648689
TI  - Linking Neighborhood Context and Health in Community-Dwelling Older Adults in the
      Medicare Advantage Program.
AB  - OBJECTIVES: To examine whether neighborhood context moderates the relationship
      between multiple chronic conditions (MCCs) and function in Medicare Advantage
      (MA) beneficiaries. DESIGN: Cross-sectional study. SETTING: Medicare Health
      Outcome Survey Cohort 16 baseline data from 2013. PARTICIPANTS: MA beneficiaries
      aged 65 and older (N=187,434). MEASUREMENTS: We defined disadvantaged
      neighborhoods as those with an Area Deprivation Index greater than the 85th
      percentile. MCCs was defined as having 2 or more chronic conditions. The primary
      outcome was any self-reported functional limitations with a basic or instrumental
      activity of daily living. We used survey-weighted multivariate linear probability
      regression to examine whether the neighborhood disadvantage moderates the
      relationship between MCCs and report of a functional limitation. RESULTS: More
      than one third (35.6%) of the sample reported a functional limitation.
      Beneficiaries with MCCs were more likely to report a functional limitation those
      with 0 or 1 chronic condition (odds ratio (OR)=2.63, 95% confidence interval
      (CI)=2.50-2.77). Beneficiaries in more-disadvantaged neighborhoods were more
      likely to report a functional limitation than those in less-disadvantaged
      neighborhoods (OR=1.14, 95% CI=1.08-1.21). In older adults with MCCs, the
      probability of reporting a functional limitation was 12 percentage points greater
      in those living in more-disadvantaged neighborhoods than in those living in less
      disadvantaged neighborhoods. CONCLUSION: Neighborhood context is a significant
      predictor of functional limitation and moderates the association between chronic
      conditions and functional limitations. Health plans and public health officials
      could use publicly available indicators such as the ADI to target interventions
      to reduce functional impairment.

PMID- 29648690
TI  - Incremental value of left atrial active function measured by speckle tracking
      echocardiography in patients with hypertrophic cardiomyopathy.
AB  - PURPOSE: Hypertrophic cardiomyopathy (HCM) impairs left ventricular (LV)
      diastolic function leading to left atrial (LA) dilatation. Because Doppler
      echocardiography cannot accurately assess LV diastolic function in hearts with
      heterogeneous hypertrophy, assessment of LA function might be useful for risk
      stratification of patients with HCM. This study aimed to elucidate the impact of
      LA function on outcome in patients with patients. METHODS: Seventy-six patients
      with HCM who underwent echocardiographic and cardiac magnetic resonance imaging
      were retrospectively enrolled. Twenty-six control subjects were also included.
      Using speckle tracking echocardiography, LA function was divided into active and
      passive strain indices based on the timing of the second positive peak of LA
      strain rate that occurred during LV systole. RESULTS: Left atrial strain indices
      of active and passive function were significantly impaired concomitantly with
      increased LA volume index in HCM patients compared with controls. During follow
      up (2.6 +/- 1.7 years), 14 patients with HCM developed cardiac events (heart
      failure hospitalization or atrial fibrillation). The association of LA active
      strain with cardiac events was independent of and incremental to clinical and
      echocardiographic parameters (age, gender, E/e', LV global longitudinal strain,
      and LA volume index) in sequential models. Cardiac events were more frequent in
      HCM patients with LA active strain <20.3% than with active strain >=20.3% (P =
      .01). CONCLUSION: Loss of LA active function was associated with increased
      cardiac events in patients with HCM.

PMID- 29648691
TI  - Implementing the End TB Strategy in the Western Pacific Region: Translating
      vision into reality.
AB  - The End TB Strategy aims to end the global tuberculosis (TB) epidemic by 2035 in
      line with the sustainable development goals targets and has been implemented in
      the World Health Organization (WHO) Western Pacific Region since 2015.
      Significant progress has been made in implementing this strategy. However,
      several challenges still remain. In 2016, an estimated 1.8 million people
      developed TB in the region, and of these about 20% were missed by national TB
      programmes. The gap in diagnosis and enrolment as well as treatment completion is
      greater with drug-resistant TB. Many TB-affected families face catastrophic costs
      due to the disease. Sustaining financing for TB care is a long-term challenge in
      many countries. This article emphasizes targeted interventions in high-risk
      populations, including systematic screening and patient-centred TB care. Several
      other approaches including improving TB diagnostic tools and algorithm, and
      engaging all care providers are suggested to find missing TB patients. Drug
      resistant TB requires additional resourcing for laboratories, enrolment and
      patient support. Specific measures are required at different levels to mitigate
      financial burden due to TB including linking TB to overall social protection
      schemes. The Moscow Ministerial conference in 2017 and upcoming United Nations
      (UN) 2018 high-level meeting provide an opportunity to raise TB higher on the
      global agenda, forge partnerships and move towards universal health coverage.

PMID- 29648692
TI  - Multimodality imaging for evaluation of chest pain using strain analysis at rest
      and peak exercise.
AB  - BACKGROUND: Exercise stress echocardiography (SE) is commonly used for diagnosing
      coronary artery disease (CAD). The use of quantitative echocardiographic measures
      such as strain imaging is expected to improve the sensitivity of conventional SE
      which relies on the visual diagnosis of wall-motion abnormalities (WMAs). This
      study is set to demonstrate the added value of resting and exercise strain
      analysis to detect underlying microangiopathy and inducible myocardial ischemia
      during a resting and SE in comparison with the results of coronary computed
      tomographic angiogram (CCTA). METHODS: A total of 103 consecutive outpatients
      from the executive screening program were identified and underwent resting and
      SE. Global longitudinal strain (GLS) and wall-motion changes at rest and peak
      exercise were analyzed and compared. Baseline demographics, heart rate, and blood
      pressure measurements were retrospectively extracted for analysis. CCTA was
      chosen as an alternative test to match with wall motion and strain imaging.
      RESULTS: Patients who had abnormal CCTA had lower resting GLS (14.85% +/- 3.05 vs
      17.99% +/- 2.88, P-value = .001) when compared to patients with normal CCTA. All
      patients who had abnormal CCTA had higher wall-motion score index (1.35 +/- 0.2
      vs 1.00, P-value < .0001) and lower and abnormal peak stress GLS (pGLS) as
      compared to patients with normal CCTA (14.89% +/- 3.35 vs 18.44% +/- 4.27, P
      value = .007). However, all patients with pGLS >= 20% had normal/nonobstructive
      CCTA. Patients with multiple comorbidities showed reduced and lower values of
      resting and pGLS (P-value < .0001), suggesting associated subclinical left
      ventricular dysfunction. CONCLUSIONS: Global longitudinal strain offers
      quantitative interpretation of the resting and SE study, detects underlying
      subclinical left ventricular dysfunction and a peak stress value more than 20%
      excludes obstructive CAD on CCTA.

PMID- 29648693
TI  - Anomalous systemic and pulmonary veins-An unusual coexistence.
AB  - A 12-year-old child presented with recurrent respiratory infections and was
      diagnosed with Scimitar syndrome. Drainage of IVC and course of aberrant arterial
      supply from aorta were not clear by echocardiogram, and hence, additional imaging
      was planned. CT unraveled the presence of a rare combination of anomalous
      pulmonary venous connection (APVC) to IVC, with near-atresia/severe stenosis of
      IVC, superior to the drainage of scimitar vein. There was a prominent azygos vein
      with preferential contrast opacification on lower limb injection.

PMID- 29648694
TI  - Safety of nifedipine in threatened preterm labor: Investigation by three
      dimensional echocardiography.
AB  - OBJECTIVE: To evaluate atrial and ventricular parameters using real time three
      dimensional transthoracic echocardiography (RT3DTTE) in women treated with
      nifedipine in the early third trimester (III-T) of pregnancy. METHODS: A
      prospective single-subject design study in a university-affiliated hospital,
      where each participant served as her own control. We studied 25 pregnant women at
      a gestational age of 25-33 weeks with TPTL prior to vs 48 hours postnifedipine
      treatment. Two-dimensional transthoracic echocardiography (2DTTE) and RT3DTTE
      were used to study 3D left atrial (LA) volumes and indexes, emptying fraction,
      left ventricular and LA cavities, and total vascular resistance (TVR). RESULTS:
      Two-dimensional transthoracic echocardiography showed a significant increase in
      LA area (from 15.2 +/- 2.62 to 16.16 +/- 2.21 mm2 , P = .02) before vs after
      nifedipine; RT3DTTE showed a significant change in LA end-diastolic volume index
      (from 23.7 +/- 4.2 to 26.75 +/- 3.8 mL/m2 , P = .008). LA end-systolic volume and
      index were not significantly different before vs after nifedipine (from 24.56 +/-
      8 to 25.3 +/- 5.5 mL, from 13.6 +/- 5.3 to 14.8 +/- 3.4 mL/m2 ); P > .05,
      respectively. E/a ratio, E-tdi, and E/E-tdi did not change significantly ([from
      2.54 +/- 4.46 to 2.54 +/- 4.1], [from 11.9 +/- 1.9 to 11.9 +/- 2], [from 7.8 +/-
      1.4 to 7.6 +/- 1.1], respectively, P > .05). Tricuspid annular plane systolic
      excursion (TAPSE) did not change significantly from 23.77 +/- 4.2 to 23.9 +/-
      3.3, P = .1. There was a significant decrease in pulmonary pressure (from 25.4 +/
      4.2 to 23 +/- 2.5 mm Hg, P = .02), in mean arterial pressure (from 80 +/- 4 to
      76 +/- 3 mm Hg, P < .001) and in TVR (from 1160 +/- 260 to 1050 +/- 206 dyne s/cm
      5 , P = .04). CONCLUSIONS: According to RT3DTTE measurements, in pregnant women
      treated with nifedipine for tocolysis, there were no detrimental cardiovascular
      effects detected 48 hours postnifedipine treatment. RT3DTTE could show accurately
      the compensatory response of the left heart to the cardiovascular changes induced
      by treatment with nifedipine.

PMID- 29648695
TI  - Silicateins, silicatein interactors and cellular interplay in sponge
      skeletogenesis: formation of glass fiber-like spicules.

PMID- 29648696
TI  - How to design an outstanding poster.
AB  - Poster sessions are an important forum for getting feedback on your results and
      engaging with the scientific community. In this instalment of the Words of Advice
      series, we provide you with a guide to designing an outstanding poster and offer
      tips on how to effectively communicate your results using your poster.

PMID- 29648699
TI  - Editorial.

PMID- 29648697
TI  - Silintaphin-1 - interaction with silicatein during structure-guiding bio-silica
      formation.

PMID- 29648700
TI  - Serial echocardiographic changes with different body positions and sleeping side
      preference in heart failure patients.
AB  - BACKGROUND: The sleeping position plays an important role in overall health in
      both healthy individuals and heart failure (HF) patients, which complain of
      increasing dyspnea when adopting left lateral decubitus position (LLDP) that
      improves when turning over to the right lateral decubitus position (RLDP).
      Several theories have been proposed to explain this preference of HF patients;
      however, the underlying mechanisms remain unclear. METHOD: We evaluated
      consecutive dilated cardiomyopathy (DCMP) patients with regard to whether they
      had a sleeping position preference and analyzed early and late left ventricular
      filling velocities, tissue Doppler recordings, tricuspid annular plane systolic
      excursion (TAPSE), and left ventricular outflow tract time-velocity integral
      (LVOT-TVI). Baseline echocardiographic parameters were obtained first by LLDP,
      followed by the supine position (SP) and finally RLDP in each position for 10
      minutes to ensure a stabilized hemodynamic milieu. RESULTS: A total of 26 DCMP
      patients were included in this study and a 78 echocardiographic examination
      performed. We detected that many HF patients preferred the right lateral
      decubitus sleeping position (RLDSP, 54%) and avoided from the left lateral
      decubitus sleeping position (LLDSP, 40%); the echocardiographic LVOT TVI and
      TAPSE parameters were statistically higher in RLDP compared to SP and LLDP.
      CONCLUSION: The echocardiographic LVOT TVI and TAPSE values as functional
      parameters of left and right ventricular function change with body position, and
      these hemodynamic changes may explain why HF patients willingly adopt RLDSP.

PMID- 29648703
TI  - Editorial Comment to Robot-assisted laparoscopic partial nephrectomy versus
      laparoscopic partial nephrectomy: A propensity score-matched comparative analysis
      of surgical outcomes and preserved renal parenchymal volume.

PMID- 29648701
TI  - Chronological changes in the epidemiological characteristics of upper urinary
      tract urolithiasis in Japan.
AB  - OBJECTIVES: To assess epidemiological and chronological trends of upper urinary
      tract stones in Japan in 2015. METHODS: Patients with a first episode of upper
      urinary tract stones in 2015 were enrolled in this nationwide survey. The study
      included all hospitals approved by the Japanese Board of Urology, therefore
      covering most of the hospitals where urologists practice in Japan. The annual
      incidence and composition of urolithiasis were evaluated by age and sex. These
      results were compared with the previous results of the nationwide surveys from
      1965 to 2005 to analyze temporal trends. RESULTS: The estimated annual incidence
      of a first-episode upper urinary tract stone in 2015 was 137.9 (191.9 in men and
      86.9 in women) per 100 000. The estimated age-standardized first-episode upper
      urinary tract stone incidence in 2015 was 107.8 (150.6 in men and 63.3 in women)
      per 100 000, which did not represent a significant increase since 2005. An
      equivalent incidence was observed in patients aged >50 years, whereas a reduced
      incidence was observed in patients aged <50 years in both sexes. The proportion
      of patients who received percutaneous nephrolithotomy and/or ureteroscopy
      increased by approximately fivefold in the past 10 years. CONCLUSIONS: The steady
      increase in the annual incidence of upper urinary tract stones since 1955 leveled
      off in 2015. The current results show novel trends in the incidence and treatment
      modalities in the nationwide surveys of urolithiasis in Japan.

PMID- 29648704
TI  - Abnormal ventricular repolarization in long QT syndrome carriers is related to
      short left ventricular filling time and attenuated stroke volume response during
      exercise.
AB  - BACKGROUND: Long QT syndrome (LQTS) carriers are characterized by abnormal
      ventricular repolarization, prolonged systole, and mechanical dispersion.
      Prolonged left ventricular (LV) systole has been shown to result in
      disproportionate shortening of LV filling in other conditions. The aim of this
      study was to assess LV filling, diastolic function, and stroke volume (SV)
      response to dynamic exercise, in a group of LQTS carriers. METHODS: Forty-seven
      LQTS carriers (45 +/- 15 years, 20 symptomatic) and 35 healthy individuals
      underwent bicycle stress echocardiogram. Electrocardiographic and
      echocardiographic measurements were obtained at rest, peak exercise, and 4
      minutes into recovery. RESULTS: Long QT syndrome carriers and controls did not
      differ in age, gender, heart rate, QRS duration, or LV ejection fraction. At
      rest, LQTS carriers had longer QTc and shorter filling time (FT). At peak
      exercise, QTc increased and remained longer than controls at recovery. A negative
      correlation was found between QTc and FT (r = -.398, P = .001) with greater fall
      in FT in LQTS carriers than in controls at peak exercise (-23% +/- 10 vs +2% +/-
      3, P < .0001). FT correlated with SV (r = +.27, P = .001), which increased more
      in controls than in LQTS carriers (+32% +/- 4 vs +2% +/- 1, P < .05). These
      differences were more pronounced in symptomatic LQTS carriers who had shorter FT
      and smaller SV at peak exercise and during recovery compared to asymptomatics (P
      < .05). CONCLUSIONS: Long QT syndrome carriers have longer QTc, but also shorter
      FT. These disturbances worsen at peak exercise (particularly in symptomatics)
      compromising LV filling and SV, hence a potential pathomechanism for adverse
      events.

PMID- 29648706
TI  - METHODS FOR OBTAINING POLY-epsilon-CAPROLACTONE FOR PRODUCING MICRO- AND
      NANOSCALE DRUG CARRIERS.
AB  - Poly-epsilon-caprolactone due to favorable properties including biocompatibiity,
      miscibility and controlled degradation is promising material for long term drug
      delivery devices preparation, especially in blend with other polymers.
      Commercially available polymer is synthesized without considering this way of
      utilization, and may contain potentially toxic residues of compounds used during
      polymerization process. Therefore, we attempt to summarize in this work available
      methods for synthesis of poly-epsilon-caprolactone using nontoxic reactants. The
      product properties important for polymer drug delivery system such as number
      average molecular weight and polydyspersity index (PDI) were included. Also we
      present known methods for purification of the polymer from catalyst residues, and
      other methods that may improve process of polymerization catalyzed by less active
      compounds.

PMID- 29648705
TI  - A rare giant congenital left atrial appendage aneurysm in a 1-day-old newborn.
AB  - Congenital left atrial appendage aneurysm (LAAA) is a very rare condition and
      occurs as a result of congenital dysplasia of musculi pectinate. These patients
      may be asymptomatic and/or may present with dyspnea, and thromboembolic events.
      The most common complications are life-threatening thromboembolic events and
      supraventricular tachyarrhythmias. Transthoracic echocardiography plays a very
      important role in the diagnosis of LAAA. Herein, we present a rare case of giant
      congenital LAAA.

PMID- 29648707
TI  - EXPERIMENTALLY-INDUCED ANIMAL MODELS OF PREDIABETES AND INSULIN RESISTANCE: A
      REVIEW.
AB  - Animal models are very common in diabetes research when rodents are mostly used
      in this regard. Although a number of animal models of type 1 and type 2 diabetes
      (T2D) are developed in last few decades, the numbers of animal models of
      prediabetes and insulin resistance are very scanty. Due to the rapidly changing
      pathogenesis of the disease and preventive study, the popularity of the
      prediabetic and insulin resistance models are largely increased in the recent
      years. Some genetically or spontaneously induced models of diabetes are used as
      models for prediabetes and insulin resistance in the early stage of their lives
      such as prediabetic SHROB rats, Zucker Diabetic Fatty (ZDF) rats, Goto Kakizaki
      rats, Otsuka Long Evan Tokushima Fatty Rats (OLETF), prediabetic BB-DP rats and
      prediabetic Chinese hamster (non-genetic model), however, these models are
      relatively expensive, not widely available compared experimentally-induced non
      genetic models hence not suitable for routine pharmacological screening of anti
      diabetic agents. In the present review, we carefully discussed the induction
      method, induction period, advantages, disadvantages and suitability of various
      non- genetic or experimentally-induced animal models of prediabetes and insulin
      resistance. We have also summa- rized the key factors of different models in a
      couple of tables to give a quick overview to the diabetes researchers in order to
      more appropriately select an authentic animal model of prediabetes and/or insulin
      resistance to achieve their specific research outcomes.

PMID- 29648708
TI  - POTENTIAL APPROACHES FOR REDUCING AMYLOID beta PRODUCTION.
AB  - Alzheimer's disease (AD), a neurodegenerative disorder, is associated with the
      mitochondrial dysfunction, defective synapses, and impaired cognition in elderly
      patients. The accumulation of amyloid beta (Abeta) in synapses and synaptic
      mitochondria is thought one of the critical pathological events of synaptic
      defect and impaired mitochondrial dynamics in AD neurons. In order to understand
      disease progression and designing therapeutic agents using available molecular
      targets, extensive research is in progress throughout the world. However, no drug
      has been reported, up to now, as effectively preventing and treating moiety for
      AD, due to hidden knowledge about exact mode of AD pathogenesis. However, some
      hypotheses based-drugs, possessing capability of regulating amyloid beta
      precursor protein, have been indicated for alleviation of psychological and
      behavioral symptoms of AD patients. This review article briefly describes the
      recent developments made for exploring the Abeta induced-mitochondrial defects in
      AD and some treatment possibilities through Abeta-targeting approaches for AD
      therapy.

PMID- 29648709
TI  - INHIBITORS OF LEUKOTRIENES SYNTHESIS: NOVEL AGENTS AND THEIR IMPLEMENTATION.
AB  - Leukotrienes (LTs) belong to pro-inflammatory mediators that are biosynthesized
      from arachidonic acid (AA), inter alia, by 5-lipoxygenase (5-LOX) enzyme in
      association with 5-LOX-activating protein (FLAP). An activation of LTs synthesis
      pathway occurs during the development and maintenance of numerous diseases such
      as asthma, anaphylactic shock, allergic rhinitis, psoriasis, rheumatoid
      arthritis, osteoporosis, as well as cardiovascular diseases, neurodegenerative
      diseases and certain types of cancer. The main goal of this review was to present
      recent advances on the new compounds influencing the LOX pathway, which are under
      going clinical studies. The mechanisms of action and possible implementations of
      these molecules in a treatment of asthma, cancer and cardiovascular diseases are
      discussed.

PMID- 29648710
TI  - CHLOROGENIC ACID: A PHARMACOLOGICALLY POTENT MOLECULE.
AB  - Chlorogenic acid (CGA; (IS,3R,4R.5R)-3-{[(2Z)-3-(3,4-dihydroxyphenyl)prop-2
      enoyl]oxy}-1,4,5-trihydroxycyclohexanecarboxylic acid) is a naturally occurring
      polyphenol mostly present in vegetables and fruits. CGA is a prominent component
      of Traditional Chinese Medicines and is known for various pharmacological
      activities such as antioxidant, antimicrobial, anti-inflammatory and
      hepatoprotective etc. This mini-review is an attempt to summarize the available
      literature in the last decade and to point out future perspectives in this area
      of research.

PMID- 29648711
TI  - DECOCTION PROCESS OPTIMIZATION AND QUALITY EVALUATION OF YI-HUANG DECOCTION BY
      HPLC FINGERPRINT ANALYSIS.
AB  - Yi Huang decoction (YHD) has been used as one of famous traditional formula
      because of its unique effectiveness against gynecological diseases. YHD is
      composed of five herbs, including the rootstock of Dioscoma opposita Thunb.
      (Dioscoreaceae), the kernel of Etayale ferx Salisb. (Nymphaeaceae), the bark of
      Phellodendron chinense Schneid. (Rutaceae), the seed of Plantago asiatica L.
      (Plantaginaceae), and the seed of Ginkgo biloba L. (Ginkgoaceae). To effectively
      control the quality, the processing method for YHD was optimized by means of
      single factor test as well as orthogonal test in this study. A completely
      validated method based on HPLC coupled with diode array detector was performed on
      a Kromasil C(18) column at 30 degrees  with mobile phase of 0.1% aqueous
      phosphoric acid and acetonitrile. As a result, HPLC fingerprint on the basis of
      the chromatographic data from 32 batches of samples was obtained, which contained
      44 common peaks. Among these common peaks, 6 peaks were identified as geniposidic
      acid, berberine hydrochloride, palmatine hydrochloride, phellodendrine chloride,
      magnoflorine, and verbascoside, respectively, based on their retention time
      relative to the standards. Meanwhile, the contents of these 6 compounds were also
      simultaneously examined. In sum, this study offered valuable information for the
      proper processing and quality control for YHD.

PMID- 29648712
TI  - THE COMPARISON OF THE STABILITY INDICATING TWO HPLC METHODS AND THEIR APPLICATION
      FOR THE DETERMINATION OF BOSENTAN IN COATED TABLETS.
AB  - Due to the raising requirements of drug quality, there is an increasing need for
      fast liquid separations of pharmaceutical substances with high efficiency and
      good resolution. The ultra-high pressure liquid chromatography (UHPLC) has been
      considered to meet this challenge. However, it was found that this fast method
      has also serious disadvantages. The range of applications of the UHPLC in the
      analysis of pharmaceutical substances and dosage forms is currently extensively
      discussed. In this study we investigated the consequences of the shortening of
      the analysis time of the liquid chromatographic method. Bosentan, a non-peptide
      antagonist of human endothelin receptors, was chosen as an example in this study,
      due to its therapeutic importance and lack of the reported analytical methods of
      the drug product. Two high-performance, reversed phase liquid chromatography
      methods with UV detection at 220 nm were developed for this purpose. Both methods
      were validated and the resulting performance characteristics were compared. The
      first separation (method A) was achieved on Kinetex column, (2.6 MU C18 1OOA, 150
      x 4.6 mm), the second-fast (method B) employed Kinetex column, (1.7 MU XB-C18
      100A 50 x 3.0 mm). Both methods were performed with a buffered mobile phase
      containing 0.1% of triethylamine in water brought to the pH 2.5 with phosphoric
      acid and methanol as the solvent A and acetonitrile as the solvent B. Gradient
      program was used and flow rate of 0.8 mL/min and 0.4 mL/min, for the methods A
      and B, respectively. The methods were validated according to the ICH guidelines
      for specificity, precision on the specified and LOQ limits, intermediate
      precision, accuracy, linearity (correlation co-efficient =0.999) and robustness.
      The robustness was confirned using four factors: the mobile phase pH, the flow
      rate of the mobile phase, column temperature and the second column of the same
      kind. The limits of detection and quantification were established as 0.0132 and
      0.1505 MUg/mL for methods A and B, respectively. Both validated methods complied
      with the acceptance criteria. The method B was 3.5 times faster than the method
      A, but the method A showed much better sensitivity. The resolution between
      compound B and bosentan was 3.39 and 1.75 for methods A and B, respectively. The
      lower sensitivity limits the use of Method B, especially in the analyses at low
      levels of active substances (e.g., bioanalysis, validation of the cleaning
      procedures) and makes method A more suitable for this purpose.

PMID- 29648713
TI  - ANALYSIS OF omega-3 FATTY ACID CONTENT OF POLISH FISH OIL DRUG AND DIETARY
      SUPPLEMENTS.
AB  - Study results indicate that a diet rich in polyunsaturated fatty acids omega-3
      (PUFA n-3) exerts favorable effect on human health, accounting for reduced
      cardiovascular morbidity and mortality. PUFA n-3 contained in marine fish oils,
      particularly eicosapentaenoic (EPA, 20:5 n-3) and docosahexaenoic (DHA, 22:6 n-3)
      acids, are attributed antithrombotic, anti-inflammatory, anti-atherosclerotic and
      anti-arrhythmic effects. They have also beneficial effects on cognitive functions
      and immunological mechanisms of an organism. Considering the fact that marine
      fish are not abundant in Western diet, the pharmaceutical industry reacts with a
      broad selection of PUFA n-3 containing dietary supplements and drugs. Increased
      consumers' interest with those products has been observed recently. Therefore,
      their quality, understood as reliability of manufacturer's declaration of
      composition of offered dietary supplements, is highly important. We have tested
      22 products available in pharmacies and supermarkets, manufacturers of which
      declared content of n-3 fatty acids (21 dietary supplements and I drug). Identity
      and content of DHA and EPA were assessed using 1H NMR spectroscopy, based on
      characteristic signals from protons in methylene groups. Almost one in five of
      the examined dietary supplements contains < 89% of the PUFA n-3 amount declared
      by its manufacturer. For a majority of tested products the manufacturer-declared
      information regarding DHA (58%) and EPA (74%) content was consistent with the
      actual composition. It is notable that more cases of discrepancy between the
      declared and the actual content regarded DHA than EPA, which indicates a less
      favorable balance, considering the pro-health effect of those acids. Over a half
      of tested products provides the supplementary dose (250 mg/day) with one capsule
      taken daily, and in 27% of cases the daily dosage should be doubled. Only 10% of
      those products ensure the appropriate dose for cardiovascular patients (1 g/day)
      with the use of I capsule a day. Correct information provided by a manufacturer
      on a label regarding the total amount of DHA and EPA is a basis for selection of
      an appropriate dosage.

PMID- 29648714
TI  - 2D LC HEART CUTTING ON-LINE OF PHENOLIC COMPOUNDS FROM THREE SPECIES OF THE GENUS
      SALIX.
AB  - The 2D LC heart-cutting on-line system was elaborated and employed to the
      analysis of simple phenols and polyphenols occurring in willow barks. Using the
      test-set of 52 compounds, the conditions of chromatographic separation in each
      dimension were optimized. The worked-up system was based on RP-separation in both
      dimensions and the use of different elution profiles on the first- and second
      dimensional columns: gradient and multistep gradient elution, respectively. In
      all analyses the UV detector was used. Under optimized separation conditions
      slightly modified in respect to chemical composition of the each analyzed MeOH
      extracts from three willow barks: Salix daphnoides, S. puiputea and S.
      sachalinensis 'Sekka' the differences in phenolie acid and flavonoid compositions
      were revealed.

PMID- 29648715
TI  - BLOCKADE OF LARGE CONDUCTANCE CA(2+) ACTIVATED K(+) CHANNEL MAY PROTECT NEURONAL
      CELLS FROM HYPOXIA MIMETIC INSULT AND OXIDATIVE STRESS.
AB  - Previous studies have linked neuronal cell death with changes of intracellular
      Ca(2+)([Ca(2+)](i)) homeostasis. Such changes of [Ca(2+)](I) has been noticed in
      various neurodegenerative models. It has also been suggested that K(+)channel,
      such as large conductance Ca(2+)-activated K(+) channel (BK), might present a
      neuronal protective effect. Hence, this study has established two cell insult
      models, oxidative stress induced by H(2)0(2) and hypoxia mimetic induced by
      CoCl(2+), on a human neuronal cell line SH-SY5Y, since both insults are related
      to neurodegeneration and are able to increase the [Ca(2+)](i). MTS assays were
      used to test the possible effect of BK activators and blockers. According to the
      results, BK activators, NS1619 and isopimaric acid (IPA), would potentiate
      toxicity to the cells under both of the two insults. But the K(+) channel
      blockers, tetraethylammonium (TEA) and tetrandrine, have presented the neuronal
      protective effect against CoCl(2), insult. Considering that [Ca(2+)](i), which
      would activate the BK channel, is the key issue in neurodegeneration, it would be
      suggested by the results from this study that K(+) channel blocker, rather than
      activator, would potentially present the neuronal protective effect.

PMID- 29648716
TI  - FLUPHENAZINE AND PERPHENAZINE IMPACT ON MELANOGENESIS AND ANTIOXIDANT ENZYMES
      ACTIVITY IN NORMAL HUMAN MELANOCYTES.
AB  - Fluphenazine and perphenazine as a phenothiazine-class antipsychotic drugs are
      widely used to treat psychoses and schizophrenia, however their use is associated
      with significant side effects such as extrapyramidal symptoms as well as ocular
      and skin disorders. The aim of this study was to examine the effect of
      fluphenazine and perphenazine on cell viability, melanogenesis and antioxidant
      defense system in normal human melanocytes. It has been shown that both
      phenothiazines induce concentration-dependent loss in cell viability. The value
      of EC50. was calculated to be 1.24 and 2.76 MUM for fluphenazine and
      perphenazine, respectively. Fluphenazine in concentration of 1.0 MUM and
      perphenazine in concentrations of 1.0 and 3.0 MUM inhibied melanogenesis and
      decreased microphthalmia-associated transcription factor content. To study the
      effect of both analyzed drugs on antioxidant defense system in melanocytes, the
      level of hydrogen peroxide and the activities of antioxidant enzymes: superoxide
      dismutase, catalase and glutathione peroxidase were determined. Fluphenazine and
      perphenazine in higher analyzed concentrations caused depletion of melanocytes
      antioxidant status, what indicated the induction of oxidative stress. The
      observed changes in melanization process and antioxidant defense system in
      pigmented cells exposed to fluphenazine and perphenazine in vibo suggest a
      significant role of melanin and melanocytes in the mechanisms of undesirable side
      effects of these drugs in vivo, especially directed to pigmented tissues.
      Moreover, the presented differences in modulation of biochemical processes in
      melanocytes may be an explanation for various toxic activity of the analyzed
      phenothiazine derivatives in vivo.

PMID- 29648717
TI  - SYNTHESIS OF IMIDAZO[2,1-b][1,3,4]THIADIAZOLE DERIVATIVES AS POSSIBLE
      BIOLOGICALLY ACTIVE AGENTS.
AB  - A series of 2-(4-methylbenzyl)-5,6-substituted-imidazo[2,1-b][1,3,4]thiadiazole
      derivatives were synthesized, characterized and evaluated for antiproliferative
      activity and cancer chemopreventive activity. Results showed that molecules with
      formyl and thiocyanate substiments at the 5 position exhibited an increase in
      activity against the full panel of 60 human tumor cell lines at a minimum of five
      concentrations at 10-fold dilutions. Derivative 22 displayed significant in vino
      anticancer activity against colon cancer (MID GI50 = 0.75 MUM). The cancer
      chemopreventive effect of 19 (IC50 = 489 nM) was almost equipotent to standard
      oleanolic acid (IC50 = 449 nM).

PMID- 29648718
TI  - SYNTHESIS, STRUCTURE AND PHARMACOLOGICAL EVALUATION OF 1-(1H-PYRROL-1-YLMETHYL)-4
      AZATRICYCLO[5.2.1.0(2,6)] DEC-8-ENE-3,5-DIONE.
AB  - A set of arylpiperazine derivatives with imide fragments, 1-(1H-pyrrol-1
      ylmethyl)-10-oxa-4-azatricyclo[5.2.1.0(2,6)-]dec-8-ene-3,5-dione connected by
      propyl and butyl linkers, were synthesized and tested for the potential
      anxiolytic and antidepressant activities. Compounds 3a and 3b demonstrated
      antidepressant activity in the forced swimming tests in mice and were devoid of
      neurotoxic effects. (chimney test in mice).

PMID- 29648719
TI  - SYNTHESIS AND PHARMACOLOGICAL ACTIVITY OF IMIDAZO[2,1- b][1,3,4]THIADIAZOLE
      DERIVATIVES.
AB  - In this paper, a series of imidazo[2,l-b][1,3,4]thiadiazoles have been prepared
      by reacting 2-amino-1,3,4-thiadiazole with various phenacyl bromides in alcohol.
      The structures of all the derivatives were con- firmed by IR, NMR and mass
      spectroscopy. All the derivatives have been tested for cytostatic activity
      against human T-lymphocyte cells (CEM), human cervix carcinoma cells (HeLa),
      murine leukemia cell line (L1210), and antiviral activity. Among the tested
      compounds, derivatives 5b, 5c, and 7a were cytostatic between 49-63 mM against
      Hela and 7g was cytotoxic at 23 mM against L1210 and CEM cell lines. Compounds 5h
      and 7h emerged as antiviral agents with slight activity against influenza A and
      B.

PMID- 29648720
TI  - PHYTOCHEMICAL ANALYSIS AND CARDIOTONIC ACTIVITY OF METHANOLIC EXTRACT OF
      RANUNCULUS MURICATUS LINN. IN ISOLATED RABBIT HEART.
AB  - Ranunculus muricatus Linn. (RML) have been traditionally used for the treatment
      of various cardiovascular disorders. The aim of present study was to evaluate
      their cardiovascular effects in isolated perfused rabbit heart. The methanolic
      extract of RML was prepared by cold maceration process. The methanolic extract of
      RML (1 ng to 10 mg) was used to determine the percentage change in force of
      contraction (FC), heart rate (HR) and perfusion pressure (PP) by using
      Langendorff's Perfused Heart Apparatus. The PP, FC and HR of isolated rabbit
      heart were measured by power lab data acquisition system. Moreover, phytochemical
      analysis and acute toxicity study were also performed. The methanolic extract at
      the doses from I ng to 10 mg exhibited a significant increase in perfusion
      pressure and force of contraction. Moreover, the crude extract of RML revealed a
      significant increase in heart rate at doses from 1 ng to MUg. The maximum rise in
      all the thee parameters was observed at 1 MUg and 1 ng, respectively In another
      study, the melhanoliC extract was tested in the presence of propranolol and
      verapamil on isolated perfused rabbit heart. The study shown that the increase in
      HR and FC produced by the plant extracts was significantly reduced in the
      presence of propranolol whereas PP remained significantly raised even in the
      presence of propranolol. However, in the presence of verapamil, this increased PP
      was significantly reversed to a decrease while a significant positive inotropic
      and chronotropic effects were observed. It is concluded that the cardiotonic
      activity of methanolic extract of RML might be due certain cardio active chemical
      compounds. Further studies are needed to isolate these pharmacologically active
      phytochemical constituents and elucidate their exact mechanism of action.

PMID- 29648721
TI  - APPLICATION OF DRY HAWTHORN (CRATAEGUS OXYACANTHA L.) EXTRACT IN NATURAL TOPICAL
      FORMULATIONS.
AB  - There is a great potential for a semi-solid preparation for topical application
      to the skin that would use materials of natural origin not only as an active
      substance but also as its base. The aim of this research was to model semisolid
      preparations containing hawthorn extract and to determine the effect of their
      bases (carriers) on the release of active components from experimental dosage
      forms, based on the results of the in vitro studies of the bioactivity of
      hawthorn active components and ex vivo skin penetration studies. The active
      compounds of hawthorn were indentified and quantified by validated HPLC method.
      The antimicrobial and anti-radical activity of dry hawthorn extract were
      evaluated by methods in vitro. The penetration of active substances into the full
      undamaged human skin was evaluated by method ex vivo. Natural topical composition
      was chosen according to the results of release of active compounds. Release
      experiments were performed with modified Franz type diffusion cells. B.ceieus was
      the most sensitive bacteria for the hawthorn extract. Extract showed antiradical
      activity, however the penetration was limited. Only traces of hyperoside and
      isoquercitrin were founded in epidermis. Protective topical preparation with shea
      butter released 41.4-42.4% of active substances. Four major compounds of dry
      hawthorn extract were identified. The research showed that extract had
      antimicrobial and antiradical activity, however compounds of hawthorn stay on the
      surface of the undamaged human skin. Topical preparation containing beeswax did
      not release active compounds. Beeswax was identified as suspending agent. Topical
      preparations released active compounds when shea butter was used instead of
      beeswax.

PMID- 29648722
TI  - EVALUATION OF ANTI-DIABETIC EFFECTS OF POLY-HERBAL PRODUCT "DIABETIC BAL" IN
      ALLOXAN-INDUCED DIABETIC RABBITS.
AB  - The current study was conducted to evaluate the anti-diabetic effect of
      polyherbal product "diabetic bal" in normal and alloxan induced diabetic rabbits.
      Glibenclamide was used as standard drug. Diabetes was induced by single i.v.
      injection of 150 mg/kg b.w. of alloxan monohydrate in rabbits. "Diabetic bal"
      (250 and 500 mg/kg) significantly decreased the blood glucose level both in
      normal and diabetic rabbits in dose dependent manner. In oral glucose tolerance
      test, "Diabetic bal" demonstrated a significant inhibitory effect on rise of
      blood glucose level compared to control. "Diabetic bal" showed synergistic anti
      hyperglycemic effect with dif- ferent units of insulin in diabetic rabbits. The
      "diabetic bal" decreased the glucose level and prevented the weight loss of
      diabetic rabbits as compared to control for an extended period of one month. It
      caused a significant increase (p < 0.001) in the insulin level of treated
      diabetic rabbits in 30 days study. In addition AST, ALT, ALP, cholesterol, LDLs,
      VLDLs and triglyceride level were significantly reduced whereas HDLs level was
      sig- nificantly elevated in diabetic rabbits with 500 mg/kg dose. The herbal
      product did not cause any significant change in CBC as compared to normal control
      in diabetic rabbits for one month. It is conceivable; therefore, that "diabetic
      bal" is effective in diabetes and its associated complications which support its
      use in folklore.

PMID- 29648723
TI  - ACTIVITY OF THYME OIL (OLEUM THYMI) AGAINST MULTIDRUG-RESISTANT ACINETOBACTER
      BAUMANNII AND PSEUDOMONAS AERUGINOSA.
AB  - Almost as soon as antibiotics were introduced to treat infectious diseases, it
      could be observed that bacteria were able to develop resistance against them.
      Currently, multidrug-resistant strains are being isolated mainly in the hospital
      environment. These are primarily non-fermenting Gram-negative bacilli, which
      exhibit both natural and acquired resistance to multiple antibiotics and
      disinfectants rendering them difficult to eradicate. The development of new,
      effective and safe substances that prevent troublesome infections is greatly
      needed to provide alternative therapeutic options for patients. There is
      increasing interest in drugs of natural origin, including essential oils. It is
      of particular interest that, although active against many bacterial strains, they
      do not contribute to antibacterial resistance against their components. The aim
      of our study was to evaluate the in vino antibacterial activity of thyme oil
      against multidrug-resistant strains of A. baumannii and P. aeriginosa using the
      disc diffusion and macrodilution methods. The strains were isolated from patients
      hospitalized in the years 2013-2014. The in vitto antibacterial activity of thyme
      oil was assessed by the disc diffusion method and the inhibition zones for the
      oil at different concentrations, produced against A. baumannii, ranged from 7 to
      44 mm. Low level of activity of thyme oil was observed against P. aeruginosa
      strains. The results of serial dilution tests confirmed the high activity of
      thyme oil against A. baumannii isolates, expressed as MIC values ranging from
      0.25 to 2 MUL/mL. These results suggest the need for further studies of
      antibacterial activity of essential oils, especially against multidrug-resistant
      bacterial isolates.

PMID- 29648724
TI  - ANALGESIC, ANTIPYRETIC AND ANTI-INFLAMMATORY ACTIVITIES OF GREWIA ASIATICA FRUIT
      EXTRACTS IN ALBINO MICE.
AB  - The present study was aimed to assess biological (analgesic, antipyretic and anti
      inflammatory) activities of methanolic and aqueous fruit extracts of Grewia
      asiatica. The study was performed on albino mice. Analgesic effect of the
      extracts was determined by acetic acid induced writhing. Antipyretic potential of
      the tested fruit extracts was assessed by brewer's yeast induced pyrexia.
      Carrageenan induced paw edema method was used to evaluate the anti-inflammatory
      activity. Both the extracts showed biological effects in a dose dependent fashion
      at doses 125 mg/kg, 250 mg/kg and 500 mg/kg orally. Analysis of variance (ANOVA)
      was used for data analysis and the values having p-value smaller than 0.05 were
      considered significant. Both the extracts had significant analgesic, antipyretic
      and anti-inflammatory activities.

PMID- 29648725
TI  - PROTECTIVE EFFECT OF POMEGRANATE SEED OIL AGAINST MERCURIC CHLORIDE-INDUCED
      HEPATOTOXICITY IN RAT.
AB  - Mercuric chloride (HgCL2) is an environmental and industrial toxicant that
      affects many tissues. Considering oxidative stress is an important component of
      mercury induced hepatotoxicity, antioxidants are expected to play a protective
      role against it. The present study was designed to investigate the probable
      effects of pomegranate seed oil (PSO) on hepatotoxicity induced by HgCL2,
      administration in rats. Rats were divided into five groups. Group 1 and 2
      received corn oil (1 mL/kg, i.p.) and PSO (0.8 mL/kg, i.p.), respectively. Group
      3 was treated with HgCl, (5 mg/kg, i.p.) for 3 days. In groups 4 and 5 PSO (0.4
      and 0.8 mL/kg i.p., respectively) was given 1 h before HgCl2 administration.
      Twenty four hours after last injection of HgCl2, blood samples and specimens of
      liver were taken. HgCl2 administration led to significant increase in liver
      malondialdehyde level, significant reduction in total sulfhydryl content and
      significant changes in serum alanine aminotransferase (ALT) and aspartate
      aminotransferase activity (AST), compared to control group. The histopathological
      changes such as necrosis, inflammatory cell infiltration and hepatocellular
      vacuolization were observed. PSO administration (0.8 mL/kg i.p.) improved the
      liver function in HgCL2 intoxicated animals as indicated by the significant
      decline in increased levels of AST, ALT in serum, MDA level and significant
      elevation in decreased total sulfhydryl content. Histological studies revealed
      milder hepatic lesions in PSO treated samples. The results indicated that
      oxidative stress may be an important mechanism of HgCl2 induced hepatic injury
      and dysfunction and PSO may be a useful agent for the prevention of HgCl2 induced
      oxidative damage in rat liver.

PMID- 29648726
TI  - COMPARATIVE BIOAVAILABILITY ANALYSIS OF ORAL ALENDRONATE SODIUM FORMULATIONS IN
      PAKISTAN.
AB  - Alendronate sodium, a bisphosphonate drug, it is used to treat osteoporosis and
      other bone diseases. The present study was designed to conduct comparative
      bioavailability analysis of oral formulations of aledronate sodium through an
      open-label, randomized, 2-sequence, 2-period crossover study. Healthy adult male
      Pakistani volunteers received a single 70 mg dose of the test or reference
      formulation of alendronate sodium followed by a 7 day washout period. Plasma drug
      concentrations were determined using a validated HPLC post column fluorescence
      derivatization method. AUC(01,) AUC(0-8,) C(max). and T(max) were determined by
      non-compartmental analysis and were found within the permitted range of 80% to
      125% set by the US Food and Drug Administration (FDA). Results show that both in
      vitio and in vivo assays of all test brands were within the spec- ification of
      the US Pharmacopoeial limits and were statistically bioequivalent. No adverse
      events were reported in this study.

PMID- 29648727
TI  - DEVELOPMENT AND CHARACTERIZATION OF SMART DRUG DELIVERY SYSTEM.
AB  - Present work concerned with development and evaluation of an innovative drug
      carrier, as smart drug delivery system for highly acid labile drug. Free radical
      polymerization technique was employed to develop pH sensitive drug delivery
      system by using carboxymethyl cellulose (polymer), methacrylic acid (monomer),
      potassium persulfate (initiator) and N,N methylene bisacrylamide (crosslinker).
      Prepared crosslinked polymer was characterized by swelling analysis at acidic and
      basic pH to evaluate pH responsive swelling, instrumental analysis (SEM, FIIR and
      thermal analysis) and pH responsive release of model drug rabeprazole sodium.
      Characterization of smart drug delivery concluded that pH responsive swelling and
      drug release parameters were directly related with methacrylic acid concentration
      in the crosslinked polymer. It was observed that by raising methacrylic acid
      contents swelling at basic pH enhanced and crosslinker contents increment reduce
      swelling. Among nine formulations with varying formulation contents, CMA2
      exhibited more pH sensitive swelling and cumulative drug release at alkaline pH.
      Results of investigation recommended that CMA2 can be a best crosslinked polymer
      as smart drug carrier.

PMID- 29648728
TI  - RELATIVE BIOAVAILABILITY STUDY OF SUCCINIC ACID COCRYSTAL TABLET AND MARKETED
      CONVENTIONAL IMMEDIATE RELEASE TABLET FORMULATION OF CARBAMAZEPINE 200 MG IN
      RABBITS.
AB  - A single-dose study was performed to observe the bioequivalence of the newly
      formulated carbamazepine-succinic cocrystal (CBZ-SUC) immediate release tablet
      (F(1)) with marketed immediate release formulation Epitoll 200 mg tablet (F(0)).
      In this study on albino rabbits, the plasma levels resulting from 250 mg
      cocrystal equivalent to 200 mg of carbamazepine and conventional tablets 200 mg
      immediate release tablets were compared. An open-label, randomized 2 x 2
      crossover study design, with a 1-week washout period, was used. Carbamazapine
      (CBZ) plasma concentrations were determined by a high-performance liquid
      chromatography validated method using ultraviolet detection. CBZ plasma levels
      were measured at predose and various postdose time points up to 72 h and the
      following pharmacokinetic parameters were used for evaluation: area under the
      curve (AUC), maximum plasma drug concentration (C(max)), time to achieve C(max),
      and elimination rate constant. (K(e)). By applying paired t-test to AUC2(0-72)
      (calculated by linear trapezoidal rule), the experimental formulation F(1), was
      found to have statistically significant (***p < 0.05) improvement in
      bioavailability of CBZ. However, these statistical differences do not have
      practical implications and the two formulations (F(0) and F(1)) were found to be
      bioequivalent as the relative bioavailability of both formulations (106.9%) falls
      with- in the acceptable FDA set range of two bioequivalent products 80-125%.

PMID- 29648729
TI  - EFFECT OF SIMULTANEOUSLY SILICIFIED MICROCRYSTALLINE CELLULOSE AND PREGELATINIZED
      STARCH ON THE THEOPHYLLINE TABLETS STABILITY.
AB  - High profitability and simplicity of direct compression, encourages
      pharmaceutical industry to create universal excipients to improve technology
      process. Prosolv(r) SMCC - silicified microcrystalline cellulose and Starch
      1500(r) - pregelatinized starch, are the example of multifunctional excipients.
      The aim of the present study was to evaluate the stability of theophylline (API)
      in the mixtures with excipients with various physico-chemical properties
      (Prosolv(r) SMCC 90, Prosolv(r) SMCC HD 90, Prosolv* SMCC 50(r), Starch 1500(r)
      and magnesium stearate). The study presents results of thermal analysis of the
      mixtures with theophylline before and after 6 months storage of the tablets at
      various temperatures and relative humidity conditions (25 +/- 2 degrees C/40 +/-
      5% RH, 40 +/- 2 degrees C/75 +/- 5% RH). It was shown that high concentration of
      Starch 1500(r) (49%) affects the stability of the theophylline tablets with
      Prosolv(r) SMCC. Prosolv(r) SMCC had no effect on API stability as confirmed by
      the differential scanning calorimetry (DSC). Changes in peak placements were
      observed just after tabletting process, which might indicate that compression
      accelerated the incompatibilities between theophylline and Starch 1500. TGA
      analysis showed loss in tablets mass equal to water content in starch. GC-MS
      study established no chemical decomposition of theophylline. We demonstrated that
      high content of Starch 1500(r) (49%) in the tablet mass, affects stability on
      tablets containing theophylline and Prosolv(r) SMCC.

PMID- 29648730
TI  - FORMULATION, EVALUATION AND IN VITRO DISSOLUTION PERFORMANCE OF ENALAPRIL MALEATE
      SUSTAINED RELEASE MATRICES: EFFECT OF POLYMER COMPOSITION AND VISCOSITY GRADE.
AB  - The present study aimed at developing the sustained release matrix tablets of
      enalapril maleate and evaluating the effect of polymer concentration and
      viscosity grade on drug release. The sustained release enalapril maleate tablets
      were successfully formulated by direct compression method using nonionic
      cellulose ethers HPMC K15, HPMC K100 and HPC polymers either alone or in
      combination. In-vitio drug release study was carried out in phosphate buffer (pH
      6.8) for a period of 24 h following USP dissolution apparatus II i.e., paddle
      apparatus. Model dependent approaches like zero-order, first order, Higuchi's
      model and Korsmeyer-Peppas model were used to assess drug release from various
      formulations. All the three polymers alone or in combination sustained the drug
      release. The drug release characteristics from HPMC and HPC polymer followed zero
      order release kinetics except for 45% concentration of all polymers alone or in
      combination where by the drug release followed Higuchi's model. In all cases, the
      drug release mechanism was both diffusion as well as erosion.

PMID- 29648731
TI  - PREPARATION AND EVALUATION OF pH RESPONSIVE POLY(2-HYDROXYETHYL METHACRYLATE-CO
      ITACONIC ACID) MICROGELS FOR CONTROLLED DRUG DELIVERY.
AB  - In this study, a series of pH sensitive microgels (MGs) were prepared by modified
      free radical suspension polymerization of 2-hydroxyethyl methacrylate (HEMA) and
      itaconic acid (IA), using ethylene glycol dimethacrylate (EGDMA) as crosslinker.
      Equilibrium swelling technique was employed for esomeprazole magnesium trihydrate
      (EMT) loading. Prepared microgels were characterized through Fourier transforms
      infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), dynamic light
      scattering technique (DLS), scanning electron microscopy (SEM), equilibrium
      swelling and in vitro drug release kinetics. FTIR and TGA confirmed the formation
      of copolymeric p(HEMA-co-IA) network. SEM and DLS revealed smooth, round and
      uniformly distributed microspheres with particle size up to 10 MUm. Developed
      microgels found to be pH responsive in nature. All the formulations (HIDI - HID5)
      followed Higuchi model with non-Fickian diffusion mechanism of drug release. It
      was concluded that p(HEMA-co-IA) microgels have potential to be used as drug
      carriers for site specific and controlled drug delivery.

PMID- 29648732
TI  - QUINIDINE AND DOMPERIDONE INTERACTIONS IN THE RAT EXPERIMENTAL MODEL OF REPEATED
      ADMINISTRATION.
AB  - This study has investigated domperidone (DOM) and quinidine (QD) interaction in
      the Wistar rat experimental model of repeated administration. We used
      nonconventional administration model consistent with occasional administration
      method. Difference in administration was related to sequence of domperidone alone
      or with quinidine dosage. Expected domperidone-quinidine interactions could have
      its origin both in the ability of quinidine to inhibit P-glycoprotein (P-gp)
      activity as well as cytochrome P450-mediated metabolism of both compounds. There
      also were examined kinetics of acetaminophen (PAM) administered (30 mg/kg) with
      domperidone as an indicator of gastric emptying, showing domperidone prokinetic
      activity, as well as quinidine anticholinergic activity. Domperidone (30 mg/kg)
      with PAM and with/without quinidine (25 mg/kg) was administered orally according
      to the disposition regiment different for six examined rat groups. DOM and PAM
      concentrations in plasma were assayed by HPLC method. Following changes were
      observed: domperidone did not modify the duration of the uptake phase of
      acetaminophen; quinidine prolongs gastric emptying time (as a result of
      anticholinergic action); quinidine given as the fourth or fifth dose with
      domperidone promotes growth of its concentration in plasma; analysis of changes
      in the value of AUC(0-2) at the initial three weeks of experiment suggests
      intensity of domperidone absorption processes, the following week increase in the
      value AUC(4-6) suggests inhibition of domperidone hepatic biotransformation and
      the mechanism of induction of absorption during domperidone administration is
      different from the absorption - inducing effects of quinidine. Both effects are
      superimposed and produce large, 2, 3-fold change in domperidone's AUC(0-6).

PMID- 29648733
TI  - EXCRETION OF ETHYL GLUCURONIDE IN THE URINE OF WARSAW HIGH PREFERRING RATS
      DEPENDS ON THE CONCENTRATION OF INGESTED ETHANOL.
AB  - Ethyl glucuronide (EtG) is a direct ethanol metabolite. The presence of EtG in
      urine can be used as a laboratory test to detect recent alcohol consumption.
      Several earlier studies in humans and in rats revealed that the same amount of
      ethanol ingested at different concentrations results in different blood ethanol
      concen- trations. The effect of different concentrations of ingested ethanol on
      the resulting EtG levels in urine was tested in WHP rats. The EtG concentration
      was also measured in rat hair. A significant (p < 0.05) decrease in the total
      amount of urine EtG after administration of the higher concentration (50%)
      ethanol solution as compared to 30% ethanol at the same dose of ethanol (3 g/kg)
      was observed. Median EtG concentration in rat hair of 1.5 ng/mg (range: 0.7-2.3
      ng/mg) was observed. Our results demonstrate that EtG production and excretion in
      WHP rats is dependent on alcohol concentration administered orally. EtG levels in
      hair closely reflect the fate of EtG in the rat.

PMID- 29648734
TI  - EFFECT OF DIETARY FLAVONOID NARINGENIN ON BONES IN RATS WITH OVARIECTOMY-INDUCED
      OSTEOPOROSIS.
AB  - Naringenin is a dietary flavanone which can be found in many products such as
      citrus fruits. This substance reveals multiple pharmacological activities such as
      antiinflammatory and antioxidative. During the menopause, the estrogen deficiency
      occurs, thus naringenin, which is also considered as a phytoestrogen, may be
      useful in the treatment of menopause-associated osteoporosis. The aim of the
      presented study was to examine the effect of naringenin on the mechanical
      properties, chemical composition and the histomorphological parameters of bones
      in the rats with ovariectomy-induced osteoporosis. The female Wistar rats were
      divided into 4 groups: sham-operated, ovariectomized, ovariectoiized treated with
      estradiol (0.2 mg/kg p.o.) and ovariectomized treated with naringenin (50 mg/kg
      p.o.), and the tested substances were administered for 4 weeks. The obtained
      results show that ovariectomy caused the characteristic changes in the skeletal
      system of rats - there was deterioration in mechanics, chemistry and
      histomorphometry. The estradiol administered to the rats served as positive
      control for the experiment. Administration of naringenin to the ovariectomized
      rats affected neither the bone chemical content nor the mechanical properties,
      however, there was a slight improvement in the bone microarchitecture in the
      tissue affected by osteoporosis. It can be concluded that the intake of
      naringenin in dietary products is not harmful and may even bring beneficial
      effect on the bones histomorphometry during postmenopausal osteoporosis.

PMID- 29648735
TI  - TELEVISION ADVERTISING OF SELECTED MEDICINAL PRODUCTS IN POLAND AND IN THE UNITED
      STATES - A COMPARATIVE ANALYSIS OF SELECTED TELEVISION COMMERCIALS.
AB  - The aim of the analysis was to establish the differences between television
      commercials of OTC drugs broadcast in Poland and in the U.S. The study covered
      100 commercials of medicinal products of various producers applied to treat a
      variety of symptoms and diseases. The analysis demonstrated that there are both
      similarities and differences. The differences concerned e.g., spot length, the
      time of placement of a brand name and the diversity of advertising slogans. The
      most significant similarities concerned applied manipulation techniques,
      locations featured in commercials and the choice of actors.

PMID- 29648736
TI  - Development of a financial literacy course for patients with newly diagnosed
      cancer.
AB  - OBJECTIVES: Although patients with cancer often face serious financial hardships,
      few studies have reported on strategies to mitigate this burden. Improving
      literacy about the financial aspects of cancer care may decrease the negative
      financial impact of cancer diagnosis and treatment. We obtained input from
      patient stakeholders on the perceived value and optimal design of a financial
      literacy program in the advanced cancer setting. STUDY DESIGN: Prospective cohort
      survey. METHODS:  A series of semi-structured interviews were conducted, during
      which patients with either colorectal or breast cancer were asked to describe the
      impact of cancer on their finances and employment, to state their preferences
      about discussing costs with their providers, and to give input on development of
      a financial literacy course. RESULTS: Twenty-one patients (76% Caucasian)
      completed interviews, the majority of whom had Medicare or commercial insurance
      (71%). Lost income from early retirement or disability was the most financially
      burdensome experience for 67% of patients. The majority of patients (76%)
      reported that a financial literacy course would be helpful in navigating the cost
      of cancer care. Most preferred the course be administered at diagnosis in a live
      group format. CONCLUSIONS: Feedback from patients with cancer supported the
      development of a group financial literacy course that addresses barriers to
      discussing cost concerns, employment changes during cancer, and available
      resources for financial assistance.

PMID- 29648737
TI  - Reducing barriers to medication access and adherence for ACA and Medicaid
      participants: a peer-to-peer, community-based approach.
AB  - OBJECTIVES: To identify how peer-to-peer support programs empower patients by
      improving health literacy and providing education on important patient issues,
      including increasing access and reducing barriers to life-saving medications and
      how these programs improve patient outcomes. STUDY DESIGN: A review of current
      literature, identification of gaps in research, and case studies. METHODS: An
      analysis of data collected from the cluster sample and a review of secondary data
      from patient case studies were used to create a theoretical framework of
      community-based, peer support services. The research examines how peer-to-peer
      support services empower and educate patients to improve access and adherence to
      critical medications. Mended Hearts is made up of such peer support groups,
      comprising heart patients and caregivers; it studies patient populations in
      addition to piloting new programs. RESULTS: Patients who receive peer-to-peer
      support services are more empowered and educated, and as a result, are able to
      make better healthcare choices and access resources that reduce many of the
      barriers that Affordable Care Act exchange and Medicaid participants face.
      CONCLUSIONS: Peer-to-peer support and education models reduce barriers to
      accessing medications and improve medication adherence, which subsequently
      improve patient outcomes.

PMID- 29648738
TI  - The increasing need for the safety net: an introduction to the Patient Access
      Network Foundation and AJMC collaborative supplement.
AB  - This supplement showcases the winning papers and case studies from the PAN
      Challenge, which aimed to stimulate a dialogue on ways to reduce or eliminate the
      barriers and disparities that Medicare and ACA enrollees face in obtaining
      medications to treat life-threatening, chronic, and rare diseases.

PMID- 29648739
TI  - Reducing out-of-pocket cost barriers to specialty drug use under Medicare Part D:
      addressing the problem of "too much too soon".
AB  - OBJECTIVES: Medicare Part D specialty drug users not qualifying for low-income
      subsidies (non-LIS beneficiaries) face high and variable cost sharing during the
      calendar year. We examined their out-of-pocket (OOP) cost patterns under the
      existing Part D cost-sharing policies and proposed changes to these policies.
      METHODS: Using 100% Medicare claims data from 2012, we examined mean annual and
      monthly OOP drug costs for Medicare Part D patients who were full-year users of
      Part D specialty drugs for rheumatoid arthritis (RA) (n = 1063), multiple
      sclerosis (MS) (n = 2256), or chronic myeloid leukemia (CML) (n = 1135) under
      existing policy. Using the same data, we simulated costs under both proposed
      Medicare Payment Advisory Commission (MedPAC) policy recommendations and our own
      recommendations. RESULTS: In 2012, our sample faced mean annual cumulative OOP
      drug costs (for all medications) of $3949 (RA), $5238 (MS), and $6322 (CML). Mean
      OOP costs were $977 (RA), $1613 (MS), and $2456 (CML) in January alone. A
      substantial proportion of total annual OOP prescription spending also occurred
      during the catastrophic coverage phase (RA: $1229 [31%]; MS: $2456 [47%]; CML:
      $3546 [56%]). Under proposed MedPAC changes, patients would have faced maximum
      annual OOP spending of $4700, but mean OOP costs in January and February would
      have been higher compared with the existing policy. Under our proposed strategy,
      OOP costs would have been spread evenly over 12 months (<=$392 per month). The
      potential incremental costs of our proposed strategy would have been $23.55 per
      non-LIS Part D beneficiary per year. CONCLUSIONS: The existing Part D cost
      sharing structure creates a substantial financial burden for specialty drug
      users, especially early in the year. Implementing both annual and monthly OOP
      maximum spending limits would result in lower, more consistent OOP costs,
      potentially increasing patients' ability to access treatments for life
      threatening, chronic, and rare diseases.

PMID- 29648740
TI  - Impact of a value-based formulary in three chronic disease cohorts.
AB  - OBJECTIVES: Value-based insurance design has been suggested as an effective
      approach to ensure access to highvalue medications in health insurance markets.
      Premera Blue Cross, a large regional health plan, implemented a value-based
      formulary (VBF) for pharmaceuticals in 2010 that explicitly used cost
      effectiveness analysis to inform medication co-payments. This study assesses the
      impact of a VBF on adherence and patient and health plan expenditures on 3
      chronic disease states: diabetes, hypertension, and hyperlipidemia. STUDY DESIGN:
      Interrupted time series design of employer-sponsored plans from 2006 to 2013.
      Beneficiaries exposed to the VBF formed the intervention group, and beneficiaries
      in similar plans without any changes in pharmacy benefits formed the control
      group. METHODS: We measured medication expenditures from member, health plan, and
      member-plus-health plan (overall) perspectives and medication adherence as
      proportion of days covered. We conducted an exploratory analysis of medication
      utilization classifying medications according to whether co-payments moved up or
      down in the year following VBF implementation. RESULTS: For the diabetes cohort,
      there was a statistically significant reduction in member and overall
      expenditures of $5 per member per month (PMPM) and $9 PMPM, respectively. For the
      hypertension cohort, there was a statistically significant reduction in member
      expenditures of $4 PMPM and an increase in health plan expenditures of $3 PMPM.
      There were no statistically significant effects on hyperlipidemia cohort
      expenditures or on medication adherence in any of the 3 disease cohorts.
      Exploratory analyses suggest that patients in the diabetes and hyperlipidemia
      cohorts were switching to higher-value medications. CONCLUSIONS: A VBF can ensure
      access to high-value medications while maintaining affordability.

PMID- 29648741
TI  - The effect of fatigability on Expanded Disability Status Scale components in
      multiple sclerosis.
AB  - Introduction: The Expanded Disability Status Scale (EDSS) is the most widely used
      disability measure inmultiple sclerosis (MS). The effect of fatigability on EDSS
      components has been underreported to date. Objective: We investigated daytime
      variability in EDSS score and EDSS components - functional scores(FS) and walking
      distance (WD) up to 500 m, in MS patients who underwent a standardized
      fatiguingexercise. Methods: Twenty-four patients with relapsing-remitting MS (n =
      7), secondary-progressive MS (n = 8)and primary-progressive MS (n = 9) were
      included. Exclusion criteria were as follows: current MS
      relapse,infection/fever/flu-like symptoms, conditions prohibiting safe exercise
      testing, current medication affectingfatigue. One trained examiner performed
      baseline (BL) and follow-up (FU) assessments (FU1 aftera standardized fatiguing
      exercise, FU2 after rest) over a single day. EDSS score change of >=1 point if
      BLEDSS score was <5.5 or of >=0.5 point if BL EDSS score was >=5.5 were
      considered clinically meaningful. Results: In progressive MS subtypes, WD
      decreased at FU1, but recovered at FU2, more so in secondary progressiveMS
      subgroup with the highest BL EDSS score. Although BL EDSS scores (median, 5.0;
      range4.0-6.5) and FS remained relatively stable over repeated assessments in the
      total group, a clinically meaningful transitory post-exercise EDSS score increase
      was observed in three patients with progressive MS. Conclusion: WD seems to be
      more influenced by fatigability than the total EDSS score, more so in
      patientswith progressive MS and higher disability. WD should be assessed after
      rest and this strategy should beimplemented into protocols of clinical trials
      recruiting patients with progressive MS phenotypes.

PMID- 29648742
TI  - Size-Dependent Localized Surface Plasma Resonance of Au Nanoparticles in Au/ZnO
      Photoanodes for Dye-Sensitized Solar Cells.
AB  - The size effect of Au nanoparticles on plasmonic ZnO dye-sensitized cells (DSSCs)
      was investigated. Different sized Au nanoparticles (~5 nm, 10 nm, and 20 nm) were
      directly deposited on ZnO nanostructures via an in situ reduction technique. The
      size and the loading of Au nanoparticle were controlled by varying the amount of
      reducing agent and the reaction time, respectively. By introducing a proper
      amount of Au nanoparticles into the photoanode, plasmon-enhanced light
      absorption, photocurrent and power conversion efficiency were demonstrated, with
      the enhancement increased with decreasing Au particle size. Overloading the
      photoanode with Au nanoparticles, however, led to a decline in photocurrent and
      thus the cell efficiency. Au/ZnO DSSCs with optimized film thickness and 5 nm-Au
      loading attained an efficiency of 3.49%, corresponding to a 59% improvement over
      that of pure ZnO DSSCs. The improvement in cell efficiency was ascribed to a
      significant increase in the photocurrent of Au/ZnO devices, as a result of
      enhanced light harvesting and reduced interfacial resistance in the photoanode.

PMID- 29648743
TI  - Relationship between serum tumor necrosis factor receptor-2 concentration and
      periodontal destruction in patients with type 2 diabetes: Cross-sectional study.
AB  - Introduction: The role of tumor necrosis factor-alpha (TNFalpha) is well
      documented in pathogenesis of chronicperiodontitis (CP) and type 2 diabetes
      (T2D). Considering short half-life of TNFalpha, tumor necrosis factorreceptor-2
      (TNFR2) is used as prosperous surrogate marker of TNFalpha activity. Objective:
      The aim was to detect TNFR2 serum concentration and correlate it with periodontal
      destructionin patients with diagnosed T2D and nondiabetics. Methods: The study
      included 85 patients divided into three groups: T2D + CP (group T2D, n = 34);
      nondiabetics+ CP (Group PD, n = 27); and healthy controls (group HC, n = 24). T2D
      was diagnosed according toWHO criteria (2013) and periodontitis was diagnosed
      using International Workshop for a Classificationof Periodontal Diseases and
      Conditions criteria (1999). TNFR2 level was measured by enzyme-linked
      immunosorbent assay (ELISA). Results: There was no difference in TNFR2 level
      among the groups (Kruskal-Wallis, p = 0.482). Significantcorrelation (Pearson's
      correlation coefficient) was observed between clinical attachment loss (CAL)
      andTNFR2 concentration in PD group (rp = -0.460, p = 0.016). In T2D group,
      correlations were observed betweenTNFR2 concentration and CAL (rp = 0.363, p =
      0.005) and periodontal inflamed surface area (PISA)(rp = 0.345, p = 0.046) and
      periodontal epithelial surface area (PESA) (rp = 0.578, p = 0.000). Conclusion:
      Higher concentration of TNFR2 was associated with higher CAL, PESA, and PISA
      scores in T2Dgroup. Contrary to that, nondiabetics with higher values of CAL
      exhibited lower concentration of TNFR2,presenting potential protective effect on
      periodontal destruction. These results imply that diabetes mayalter TNFR2
      secretion originated from periodontium.

PMID- 29648744
TI  - Comparative effects of riboflavin, nicotinamide and folic acid on alveolar bone
      loss: A morphometric and histopathologic study in rats.
AB  - Introduction: Periodontitis is a chronic inflammatory and osteolytic disease.
      Vitamin B complex is a classof water-soluble vitamins that play important roles
      in cell metabolism. Objective: The aim of this study was to evaluate the effects
      of riboflavin (RBF), nicotinamide (NA), andfolic acid (FA) on alveolar bone loss
      in experimental periodontitis rat model. Methods: Sixty-four male Wistar rats
      were randomly divided into the following eight groups: Control,Ligated, RBF50
      (RBF, 50 mg/kg daily), NA50 (NA, 50 mg/kg daily), FA50 (FA, 50 mg/kg daily),
      RBF100 (RBF,100 mg/kg daily), NA100 (NA, 100 mg/kg daily), and FA100 (FA, 100
      mg/kg daily). Periodontitis was inducedusing silk ligature around the right first
      mandibular molar. After 11 days the rats were sacrificed.Mandible and serum
      samples were collected. Changes in alveolar bone levels were measured
      clinically,and periodontal tissues were examined histopathologically. Serum IL
      1beta (pg/ml) levels were analyzedby using ELISA. Results: Mean alveolar bone
      loss in the mandibular first molar tooth revealed to be significantly lowerin
      RBF100 group than in the Control group. In the Ligated group, alveolar bone loss
      was significantlyhigher than in all other groups. The ratio of presence of
      inflammatory cell infiltration in the Ligated groupwas significantly higher than
      in the Control group. The differences in the serum IL-1beta levels betweenthe
      groups were not statistically significant. Osteoclasts that were observed in the
      Ligated group weresignificantly higher than those of the Control and FA100
      groups. The osteoblastic activity in the Ligatedgroup, RBF100, and NA100 groups
      were shown to be significantly higher than those in the Control group.
      Conclusion: This study has demonstrated that systemic administration of RBF, NA,
      and FA in differentdosages (50-100 mg/kg) reduced alveolar bone loss in
      periodontal disease in rats.

PMID- 29648745
TI  - Cytotoxicity investigation of a new hydroxyapatite scaffold with improved
      structural design.
AB  - Introduction: Biodegradable porous scaffolds are found to be very promising bone
      substitutes, actingas a temporary physical support to guide new tissue
      regeneration, until the entire scaffold is totallydegraded and replaced by the
      new tissue. Objective: The aim of this study was to investigate cytotoxicity of a
      synthesized calcium hydroxyapatitebasedscaffold, named ALBO-OS, with high
      porosity and optimal topology. Methods: The ALBO-OS scaffold was synthesized by
      the method of polymer foam template. The analysisof pore geometry and scaffold
      walls' topography was made by scanning electron microscope (SEM). Thebiological
      investigations assumed the examinations of ALBO-OS cytotoxicity to mouse L929
      fibroblasts,using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromidefor
      (MTT) and lactate dehydrogenase(LDH) tests and inverse phase microscopy. Results:
      The SEM analysis showed high porosity with fair pore distribution and interesting
      morphologyfrom the biological standpoint. The biological investigations showed
      that the material is not cytotoxicto L929 cells. Comparison of ALBO-OS with Bio
      Oss, as the global gold standard as a bone substitute,showed similar results in
      MTT test, while LDH test showed significantly higher rate of cell
      multiplicationwith ALBO-OS. Conclusion: The scaffold design from the aspect of
      pore size, distribution, and topology seems to be veryconvenient for cell
      adhesion and occupation, which makes it a promising material as a bone
      substitute.The results of biological assays proved that ALBO-OS is not cytotoxic
      for L929 fibroblasts. In comparisonwith Bio-Oss, similar or even better results
      were obtained.

PMID- 29648746
TI  - Tensor fascia lata flap is a workhorse for defects after inguinal lymph node
      block dissection.
AB  - Introduction: Enlarged inguinal lymph nodes very often present a site of
      metastatic disease. Inguinallymph node block dissection is a demanding procedure,
      which usually requires at least one of reconstructivemodalities. Among different
      reconstruction options we selected the tensor fascia lata (TFL)musculocutaneous
      flap. Objective: The paper aims at presenting a series of inguinal block
      dissections, followed by immediatereconstruction, using the TFL flap, and
      evaluation of tumor type, flap dimension, complication rate andthe duration of
      hospital stay. Methods: We present a consecutive case series of 25 conducted
      block dissections. The defects werereconstructed using TFL flap, because of the
      extent and site of the tissue defects, reliability of the flap,and potentially
      primarily infected exulcerated tumors. Results: The reconstruction was successful
      in all cases, the incidence of surgical complications was 16%,no further
      complications, such as lymphedema or gait disturbances, were noted. Primary skin
      tumorswere predominant (13 cases), followed by genitalia tumors (four cases). The
      male sex was more frequentlyaffected (14 vs. 11 cases). Conclusion: Having in
      mind that TFL presents as a flap of adjustable size, length, shape, and
      volume,with negligible donor site morbidity, and after comparing of our results
      to those of other authors, weadvise broader use of TFL flap. As a reliable flap,
      not too difficult to harvest, with a low complication rate,it must be taken into
      consideration regarding the benefits for the patient, and, on the other hand,
      thesurgery cost and duration.

PMID- 29648747
TI  - Results of open tibial fracture treatment using external fixation.
AB  - Introduction: Open lower leg fractures are the most common open fractures of the
      locomotor systemand their treatment is associated with a number of complications.
      Objective: The aim of the paper was to present the results of the treatment of 68
      patients with open lowerleg fractures, as well as the complications that
      accompany the treatment of these fractures. Methods: In the analyzed group, there
      were 45 (66.18%) men and 23 (33.82%) women. The majority ofpatients - 33 (48.53%)
      of them - were injured in motor vehicle accidents, whereas 24 (35.29%)
      patientssustained injuries due to falls from heights. In two (2.94%) patients the
      cause of open tibial fractureswas gunshot injuries. In the analyzed group, there
      were 18 (26.47%) type I open fractures, 21 (30.88%)type II open fractures, 19
      (27.94%) type IIIA open fractures, seven (10.29%) type IIIB open fractures,
      andthree (4.41%) type IIIC open fractures. Results: The tibial shaft fracture
      healed without serious complications in 50 (73.53%) patients, whereasin 18
      (26.47%) patients we observed some complications. Nonunion was found in 10
      (14.71%) patients,osteitis in four (5.88), malunion in two (2.94%) patients.
      Milder complications such as soft tissue pintract infection developed in 13
      (19.12%) patients, infection of the open fracture wound soft tissue wasobserved
      in four (5.88%) patients. Conclusion: Basic principles in the treatment of open
      lower leg fractures in this study are thorough primaryopen fracture wound
      treatment followed by the delayed wound closure, stable fracture fixationusing
      unilateral external skeletal device, proper antibiotic treatment and tetanus
      prophylaxis. The resultscorrelate with similar studies.

PMID- 29648748
TI  - Synthesis of Different Shapes ZnFe2O4-BiOCl Nanocomposites for Photocatalytic
      Reduction of CO2 in Cyclohexanol.
AB  - Nanosheet and hierarchical microsphere nanostructures of ZnFe2O4-BiOCl
      nanocomposites with various ZnFe2O4 contents were prepared through hydrothermal
      deposition method. The morphology and structure of the as-prepared samples were
      systematically characterized by field emission scanning electron microscopy,
      transmission electron microscopy, X-ray diffraction, X-ray photoelectron
      spectroscopy, UV-vis diffuse reflectance spectroscopy, Brunauer-Emmert-Teller
      method, and photoluminescence spectra. The photocatalytic activities of the two
      different shapes of ZnFe2O4-BiOCl composites have been evaluated by
      photocatalytic reduction of CO2 in cyclohexanol under UV light irradiation. The
      results showed that cyclohexanol was oxidized to cyclohexanone (CH), and CO2 was
      reduced and then reacted with cyclohexanol to produce cyclohexyl formate (CF).
      The ZnFe2O4-BiOCl composites with different shapes showed much higher CF and CH
      yields than those of pristine BiOCl and mechanically mixed samples, respectively.
      When the ZnFe2O4 content in the composites reached 9%, two different shapes of
      ZnFe2O-BiOCl composites both achieved the highest photocatalytic activities. In
      contrast, the activities for photocatalytic reduction of CO2 in cyclohexanol over
      hierarchical microsphere ZnFe2O4-BiOCl composites were higher than those of
      nanosheet structure samples. The higher activities over hierarchical microsphere
      composites could be attributed to its unique hierarchical structure, large
      illumination area, and low Photoluminescence (PL) emission intensity, which were
      beneficial for the separation of photogenerated charge carriers. This work
      provided a novel approach for the design and construction of highly efficient
      photocatalyst and reaction system for photoreduction of CO2.

PMID- 29648749
TI  - Human papillomavirus infection prevalence in female university students in Novi
      Sad, Serbia.
AB  - Introduction: Cervical cancer, attributed to human papillomavirus (HPV)
      infection, represents the fourthmost common and lethal cancer in Serbian women,
      and the second most common cancer in womenaged 15-44. Objective: The aim of the
      study was to determine the presence of high-risk and low-risk HPV types
      inpopulation of unvaccinated female university students in Novi Sad, Serbia, and
      to evaluate possible riskfactors for HPV infection. Methods: Sample consisted of
      250 young women (19-26 years of age) attending outpatient clinics forscreening
      gynecological examination. All participants in the study completed a specially
      designed anonymousquestionnaire. For the detection of HPV DNA, two commercial
      kits - High Risk HPV Real-TM andLow Risk HPV 6/11 Real-TM (Sacace
      Biotechnologies, Como, Italy) were used. Thirty positive samples wereretested by
      GenoFlow HPV Array Test (DiagCor Bioscience Incorporation Limited, Hong Kong,
      China). Results: The overall prevalence rate of HPV was 61.6%. The most common
      HPV types in the presentstudy were as follows: HPV 16, 31, 51, 52, and 18. Female
      students with only one sexual partner hadsignificantly lower chance of having HPV
      infection. Other variables describing lifestyle did not showstatistical
      significance. Conclusion: The present paper provides data on the prevalence of
      high- and low-risk HPV genotypesamong university students in Novi Sad. Obtained
      results indicate the need for educational activities onsexually transmitted
      infections, including HPV, together with promotion of healthy lifestyles.
      Accordingto our results, bivalent and quadrivalent prophylactic vaccines have the
      potential to prevent over 50% ofinfections. Percentage of protection with a
      second-generation prophylactic nonavalent vaccine wouldbe more than 80%.

PMID- 29648750
TI  - Microstructure and Thermal Conductivity of Carbon Nanotube Reinforced Cu
      Composites.
AB  - Microstructure and thermal conductivity (TC) of carbon nanotubes reinforced Cu
      (CNT-Cu) composites have been studied. When CNTs were coated with nano Cu by
      electroless plating, the TC of CNT-Cu composites showed a noticeable improvement
      and increased with CNT contents. When 1.0 vol% CNTs was added, the TC of CNT-Cu
      composites increased to 420.4 W/(m . K), 30% higher than that of monolithic Cu
      (323.1 W/(m . K)). According to the measured TC of CNT-Cu composites, the
      interfacial thermal resistance of CNT-Cu composites was calculated as 3.0 * 10-9
      m2 K/W which was lower than the reported values of CNTs reinforced polymer matrix
      composites and ceramic matrix composites. Microstructures showed that CNTs
      modified with nano Cu were homogeneously dispersed and embedded in the Cu matrix,
      indicating that there was strong bonding between CNTs and Cu. The homogeneously
      dispersed CNTs and reduction of interfacial thermal resistance resulted in the
      improvement of thermal conductivity of CNT-Cu composites. Therefore, the prepared
      CNT-Cu composites are promising materials for thermal management applications.

PMID- 29648751
TI  - Detection of carbapenemase genes in Klebsiella pneumoniae isolates.
AB  - Introduction: Klebsiella pneumoniae is one of the leading causes of serious
      hospital-acquired infectionsworldwide among Enterobacteriaceae species. It is the
      most common producer of carbapenemases inmany parts of the world. Objective: The
      aim of the study was to determine which enzymes were responsible for resistance
      tocarbapenems in Klebsiella pneumoniae strains isolated at the Centre of
      Microbiology of Public HealthInstitute of Vojvodina. Methods: A total of 29
      Klebsiella pneumoniae non-duplicated strains resistant to at least one
      carbapenemisolated from clinical samples of hospitalized patients between
      November 1st 2013 and April 30th2014 were studied. The species identification and
      susceptibility were done using VITEK 2 (bioMerieux,Marcy-l'Etoile, France)
      system. Phenotypic conformation of carbapenemase production was done bydouble
      disc synergy test. PCR technique was performed for detection of genes encoding
      production ofcarbapenemases (bls(KPC), bla(VIM), bla (NDM), bla(OXA-48)).
      Results: Isolates of Klebsiella pneumoniae resistant to at least one carbapenem
      showed positive on double-disc synergy test between meropenem and dipicolinic
      acid. All strains positive in phenotypic testcontained bla(NDM) gene. In isolates
      resistant only to ertapenem, neither production of carbapenemasesnor presence of
      genes encoding these enzymes were detected. Among these isolates, nine
      producedextended-spectrum beta-lactamase. Conclusion: The presence of NDM metallo
      beta-lactamase was determined in all Klebsiella pneumoniaeisolates resistant to
      at least one carbapenem.

PMID- 29648752
TI  - The role of apraclonidine in Horner's syndrome - A case report.
AB  - Introduction: Horner's syndrome is an interruption of the sympathetic nervous
      system at any pointalong its course between the hypothalamus and the orbit.
      Horner's syndrome is classically presentedas an ipsilateral miosis, subtle
      ptosis, and facial anhidrosis. Pharmacologic testing is very useful in
      thediagnosis of Horner's syndrome as it could help to localize the lesioned
      neuron in the sympatheticpathway, suggesting an etiology. Case Outline: We
      present a case report of a 41-year-old woman who reported right eyelid drooping
      immediatelyafter operation of sympathetic chain schwannoma. We performed
      apraclonidine test for thediagnosis of Horner's syndrome, which produced
      mydriasis on the affected eye, while there was no significantchange of the normal
      eye. Based on the clinical presentation of anisocoria and one-sided ptosis,and
      previous medical history of surgical removal of the mediastinal tumor, the
      patient was diagnosedwith a right-sided, partial Horner's syndrome. Conclusion:
      Timely recognition, exact localization of the lesioned neuron, and referral for
      urgent imagingstudies are important for ophthalmologists in order to prevent and
      treat life-threatening conditions.Besides its diagnostic value in Horner's
      syndrome, topical apraclonidine could correct ptosis for the sakeof esthetics or
      when ptosis reduces the superior visual field.

PMID- 29648753
TI  - Recurrent malignant otitis externa with multiple cranial nerve involvement: A
      case report.
AB  - Introduction: Necrotizing otitis externa is a rare but conditionally fatal
      infection of external auditory canalwith extension to deep soft tissue and bones,
      resulting in necrosis and osteomyelitis of the temporal boneand scull base. This
      condition is also known as malignant otitis due to an aggressive behavior and
      poortreatment response. Early diagnosis of malignant otitis is a difficult
      challenge. We present an illustrativecase of necrotizing otitis externa and
      suggest some strategies to avoid diagnostic and treatment pitfalls. Case Outline:
      A 70-year-old patient presented with signs of malignant otitis externa,
      complicated byperipheral facial palsy. Adequate diagnostic and treatment
      procedures were performed with clinicalsigns of resolution. The recurrence of
      malignant infection had presented three months after previousinfection with
      multiple cranial nerve neuropathies and signs of jugular vein and lateral sinus
      thrombosis.An aggressive antibiotic treatment and surgery were carried out,
      followed by substantial recovery of thepatient and complete restoration of
      cranial nerves' functions. Conclusion: Necrotizing otitis externa is a serious
      condition with uncertain prognosis. The suspicion ofmalignant external otitis
      should be raised in cases of resistance to topical treatment, especially in
      patientwith predisposing factors. Evidence-based guideline for necrotizing otitis
      externa still doesn't exist andtreatment protocol should be adjusted to
      individual presentation of each patient.

PMID- 29648754
TI  - Acute renal failure and hepatocellular damage as presenting symptoms of type II
      aortic dissection.
AB  - Introduction: Pericardial effusion can be a consequence of a number of
      pathological conditions, and assuch it can cause impaired left ventricular
      filling followed by decreased cardiac output and blood pressure.This kind of
      hemodynamic compromise and its consequences are extremely uncommon
      unlesspericardial effusion causes tamponade. Case Outline: We describe a very
      rare case of a 30-year old male patient, with an acute aortic dissectiontype II
      causing pericardial effusion without clinical nor echocardiographic signs of
      tamponade, whilepresenting with an acute renal and hepatic failure. After initial
      diagnostic uncertainties, and followingfinal diagnosis of an acute aortic
      dissection, this patient underwent surgical aortic valve replacementwith a
      satisfactory outcome. Conclusion: It is important to underscore the significance
      of clinical situation of simultaneously existingacute renal and hepatic failures
      in the setting of a "non-tamponade" pericardial effusion, following atype II
      aortic dissection. Although most commonly aortic dissection presents itself with
      typical clinicalsymptoms or patient history data, it is not that unusual for it
      to be hidden in an entirely atypical clinicalmilieu as the one described in this
      case.

PMID- 29648755
TI  - Early post-transplant lymphoproliferative disorder - Case of fatal lymphoma after
      kidney transplantation.
AB  - Introduction: Post-transplant lymphoproliferative disorder (PTLD) is a common
      malignancy followingorgan transplantation. Risk for PTLD is associated with the
      use of anti-thymocyte globulin in the preventionand treatment of acute rejection
      following kidney transplantation. Case Outline: We report a case of fatal PTLD
      presented with sudden onset of fever. A 33-year-old malepatient with primary
      diagnosis of left kidney agenesia underwent kidney transplantation six years
      followinghemodialysis treatment initiation. Deceased donor was a 66-year-old
      female whose cause of deathwas cerebrovascular accident. Immunosuppressive
      regimen consisted of basiliximab, corticosteroids,tacrolimus, and mycophenolate
      mofetil. Six months upon transplantation the patient was hospitalizeddue to fever
      of unknown origin. All microbiological samples were negative, but abdominal
      ultrasoundrevealed round solid mass in the right native kidney. Right nephrectomy
      was performed showing tumor35 * 35 * 20 mm in size within the 70 * 40 * 35 mm
      kidney. Pathohistological analysis confirmed veryrare monomorphic B-cell PTLD - B
      cell lymphoma, unclassifiable, with features intermediate betweendiffuse large B
      cell lymphoma and classical Hodgkin lymphoma. Conclusion: We consider this case
      of PTLD following kidney transplantation particular because of thetumor mass in
      native kidney after basiliximab induction and rare pathohistology. In a
      transplanted patientwith fever, PTLD must always be considered, irrespective of
      immunosuppressive regimen.

PMID- 29648756
TI  - Synthesis and Spark Plasma Sintering of Soft Magnetic Composite in a Fe2O3-Al
      System by Mechanical Alloying.
AB  - We have applied mechanical alloying (MA) to produce soft magnetic composite
      material using a mixture of elemental Fe2O3-Al powders. An optimal milling and
      sintering conditions to obtain soft magnetic alpha-Fe/Al2O3 composite with fine
      microstructure were investigated by X-ray diffraction, differential scanning
      calorimeter and vibrating sample magnetometer measurements. It is found that the
      average grain sizes of alpha-Fe in alpha-Fe/Al2O3  composite ball-milled for 5
      hours is estimated to be in the range of 50 nm. The saturation magnetization of
      ball-milled powders showed a maximum value of 88 emu/g after 30 min. of MA and
      reaches to 77 emu/g after 5 h of MA. The magnetic hardening due to the reduction
      of the alpha-Fe grain size with ball milling was also observed. Densification of
      the ball-milled powders was performed in the spark plasma sintering (SPS) machine
      at 1000  degrees C and 1100  degrees C. FE-SEM observation shows that the average
      grain size of alpha-Fe in alpha-Fe/Al2O3 composite sintered at 1000  degrees C is
      in the range of 100 nm, which is nearly same value estimated from the so-called
      Hall plot. It can be also seen that the coercivity of SPS sample sintered at 1000
      degrees C is still high value of 92 Oe, suggesting that the grain growth of
      magnetic alpha-Fe phase during SPS process tends to be suppressed.

PMID- 29648757
TI  - Metastatic malignant melanoma of the uterus diagnosed by colposcopy.
AB  - Introduction: Primary and metastatic malignant melanomas represent a rare
      diagnosis with a small numberof described cases. The aggressive nature of the
      tumor, non-specific symptoms, difficult diagnosis,and no official protocol about
      the treatment result in poor disease prognosis. Case Outline: The authors
      presented a 41-year-old multigravida patient. She had an operation of
      malignantmelanoma in the occipital area of the head. She went to her gynecologist
      because of increased palepink vaginal secretion. Gynecological examination didn't
      show any significant abnormalities apart from aslightly enlarged uterus.
      Papanicolaou test and vaginal secretion examination were normal.
      Colposcopically,a significant dark brown hyperpigmented area around 1 cm in size
      was observed on the posterior lipof the cervix, near the orifice and cervical
      canal, suspicious of melanoma, which was proven on targetedbiopsy of the
      hyperpigmented change on the cervix, and by magnetic resonance imaging of the
      lesserpelvis. Classic hysterectomy with adnexectomy and regional pelvic
      lymphadenectomy were performed. Conclusion: This case report pointed out the
      significance of applying colposcopy in diagnosing suspectedmetastatic melanoma of
      the uterine cervix, along with other diagnostic methods and anamnestic data.

PMID- 29648758
TI  - Anorectal melanoma and seborrheic dermatitis - A case report.
AB  - Introduction: Anorectal melanoma (ARM) is a rare and aggressive neoplasm with
      predisposition for earlyinfiltration, distant spread, and unfavorable prognosis.
      It has been speculated that Malassezia yeastscould possibly have an impact on
      skin carcinogenesis and development of melanoma, especially inpatients with
      seborrheic dermatitis (SD), due to production of aryl hydrocarbon receptor (AhR)
      agonists. Case Outline: A 52-year-old man with intensive SD complained of a four
      month-long rectal bleeding,tenesmus, pain, and difficulty during defecation. On
      examination, a rectal tumor was detected and histopathologyof tumor tissue
      revealed ARM with positive protein S100, melanoma antigen HMB45 andmelan-A
      expression. After the diagnosis was established, abdominoperineal resection of
      the anus andrectum was performed, since the tumor was large, obstructive, and the
      anal sphincter was invaded. Conclusion: Because of the possible impact of
      intensive SD to the cross-link between Malassezia yeasts AhRagonists and skin
      carcinogenesis, we discussed on this matter and reviewed the literature data
      regardingARM. In addition to "pathogenic" and "non-pathogenic" Malassezia
      subtypes based on AhR agonist production,future studies on Malassezia
      metabolites, their carcinogenic effect in the skin and development ofmelanoma are
      needed. If the cross-link between Malassezia AhR agonists and skin carcinogenesis
      exists,timely prevention of ARM could be done with Malassezia eradication,
      especially in patients with severe SD.

PMID- 29648759
TI  - Laterality in living beings, hand dominance, and cerebral lateralization.
AB  - To date, lateralization in living beings is a phenomenon almost mythologically
      unexplored. Scientistshave proved that lateralization is not exclusively a human
      feature. Investigations in molecular biology,protein structure, mobility of
      bacteria, and intracellular lateralization in ciliates, shows important
      anduniversal nature of lateralization in living systems. Dominant lateralization
      implies the appearance of adominant extremity, or a dominant sense during the
      performance of complex psychomotor activities.Hand dominance is usually defined
      as a tendency to use one hand rather than another to perform mostactivities and
      this is considered to be the most obvious example of cerebral lateralization and
      exclusivecharacteristic of humans. However, there are some exceptions in other
      species. The dominant hand isable to perform more complex and subtle manual tasks
      than the non-dominant hand, and this behavioralsuperiority is the absolute result
      of additional cerebral support. The asymmetry of brain organizationwas confirmed
      in rats, chimpanzees, dogs and birds, some fishes and lizards. The relationships
      betweenhand dominance with brain structure and function remain far from clear.
      For a long time, lateralizationwas considered unique to humans, but recently it
      has become clear that lateralization is a fundamentalcharacteristic of the
      organization of brain and behavior in all vertebrates. It has been questioned to
      whatextent lateralization in humans and other vertebrates may be comparable.

PMID- 29648760
TI  - Current issues on sublingual allergen-specific immunotherapy in children with
      asthma and allergic rhinitis.
AB  - In 1993 the European Academy of Allergy and Clinical Immunology was the first
      official organizationto recognize that sublingual administration could be
      "promising route" for allergic desensitization. Afew years later, the World
      Health Organization recommended this therapy as "a viable alternative to
      theinjection route in adults." The first meta-analysis showed sublingual allergen
      specific immunotherapy(SLIT) effectiveness for allergic rhinitis and another
      study showed SLIT can actually help prevent thedevelopment of asthma both in
      adults and in children. The main goal of this review article is to presentinsight
      into the most up-to-date understanding of the clinical efficacy and safety of
      immunotherapy inthe treatment of pediatric patients with allergic rhinitis and
      asthma. A literature review was performed onPubMed from 1990 to 2015 using the
      terms "asthma," "allergic rhinitis," "children," "allergen specific
      immunetherapy." Evaluating data from double-blind placebo-controlled randomized
      clinical trials (DB-PC-RCTs),the clinical efficacy (assessed as the reduction of
      symptom score and the need of rescue medicament)of SLIT for allergic rhinitis and
      allergic asthma, has been confirmed in various meta-analysis Outcomessuch as
      rhinoconjunctivitis score and medication scores, combined scores, quality of
      life, days with severesymptoms, immunological endpoints, and safety parameters
      were all improved in the SLIT-tabletcompared with placebo group. SLIT safety has
      been already proven in many DB-PC-RCTs and real-lifesettings. In accordance with
      all of the above mentioned, the goals for future trials and studies are
      thedevelopment of comprehensive guidelines for clinical practice on
      immunotherapy, embracing all thedifferent potential participants. The importance
      of allergen immunotherapy is of special relevance inthe pediatric age, when the
      plasticity and modulability of the immune system are maximal, and
      whenpreventative effects can be reasonably expected.

PMID- 29648761
TI  - Post-Annealing Effect on Magnetic, Electrical, and Adhesive Properties of FePdB
      Thin Films.
AB  - FePdB was sputtered on glass substrate at room temperature (RT) to thicknesses of
      1000 A, 2000 A, 3000 A, 4000 A and 5000 A with post-annealing treatment at 150 
      degrees C and 250  degrees C. X-ray diffraction (XRD) revealed that each FePdB
      thin-film yielded a significant FePd (111) crystalline peak with a 2theta of
      41.17 degrees . As the film thickness increased with the annealing temperature,
      the FePd (111) crystallinity became stronger. The FePd (111) texture induced the
      magneto crystalline anisotropy, which reduced electrical resistivity (rho) and
      was associated with increased low-frequency alternative-current magnetic
      susceptibility (chiac). The value of chiac increased with the thickness and post
      annealing temperature due to magneto crystalline anisotropy. The maximum value of
      chiac was 4.2, which was obtained at a thickness of 5000 A with post-annealing
      250  degrees C at the optimal resonance frequency (f res) of 250 Hz, and
      corresponded to the highest spin sensitivity. The resistivity (rho) fell as the
      FePdB thickness and post-annealing temperature increased, because the grain
      boundaries and the thin-film surface scattered the electrons. The 5000 A-thick
      FePdB thin film that was post-annealed at 250  degrees C had the lowest rho,
      which was approximately 246 MUOmega . cm. Adhesion critically affects the surface
      energy of a film. The surface energies of the as-deposited FePdB films herein
      exceeded those of the post-annealed films, revealing that the adhesion of as
      deposited FePdB films was stronger than that of post-annealed films, owing to
      different degrees of crystallinity. According to the chiac and rho values of the
      films, the 5000 A-thick FePdB thin film that was post-annealed at 250  degrees C
      was the best suited to magnetic and electric component applications. The as
      deposited 1000 A-thick FePdB had the highest surface energy and adhesion, and can
      be combined with other layers in various applications.

PMID- 29648762
TI  - [Recommendation for gastroprotection in gastrointestinal bleeding prevention].
AB  - Incidence of gastrointestinal bleeding in most populations isabout 1 per 1,000
      inhabitants. More than 65% of all bleedingepisodes are associated with drug use.
      The most often involvedare non-steroidal antiinflammatory drugs and low doses
      ofacetyl-salicylic acid. The mortality within the first month afterthe bleeding
      episode is about 10-12%, and has not significantlychanged in the last decade.
      Therefore, bleeding prevention isof major importance. Appropriate selection of
      patients, properdrug choice, application of lowest efficient doses of
      potentiallyulcerogenic drugs, and use of drugs that inhibit gastric acidsecretion
      remain cornerstone preventive measures of gastrointestinalbleeding.

PMID- 29648763
TI  - Sudden cardiac death and guidelines for pre-participation examination in
      athletes.
AB  - Incidence of sudden cardiac death (SCD) in athletes under 35 years of age is
      between 0.4 and 4.4 in100,000. The highest mortality is seen in older athletes
      (>=35 years) who engage in running, mostly becauseof complications of
      atherosclerotic coronary ischemic disease. Majority of European countries
      areguided by European Society of Cardiology's (ESC) pre-participation screening
      (PPS) recommendationsthat include electrocardiography (ECG), while in the United
      States of America the ECG is not a routinepart of the PPS examination. In Serbia,
      the ESC guidelines are being used, but there are no referencesprescribed by the
      Ministry of Health. The authors of this study believe that the national strategy
      for sportimprovement should be accompanied with clear and well defined PPS
      recommendations that could betenable in our health system.

PMID- 29648764
TI  - Covalent Functionalization of Multi-Walled Carbon Nanotubes Surface via Chemical
      Treatment.
AB  - Due to the strong hydrophobic and van der Waals interactions between individual
      carbon nanotubes (CNTs), these particles easily aggregate with themselves. When
      CNTs were introduced into a polymer matrix as a filler, aggregations formed that
      can adversely affect the mechanical and thermal properties of polymer/CNTs
      composites. To prevent aggregation, covalent functionalizations via chemical
      treatments using H2SO4/HNO3, H2O2/H2O and a silane coupling agent(STX)
      glycidoxypropyltrimethoxysilane, GPTMS) on the CNTs were chosen in this study.
      Moreover, the effect of the functional groups on the solubility of CNTs in
      tetrahydrofuran (THF) was investigated. The surface-modified multi-walled carbon
      nanotubes (MWCNTs) were also characterized and compared with pristine MWCNTs
      using several techniques. Morphology changes in surfacemodified MWCNTs were
      observed by Raman spectroscopy and Field-Emission Scanning Electron Microscopy
      (FE-SEM) images. Qualitative analyses of the functional groups on the surface
      modified MWCNTs were performed by Fourier Transform Infrared Spectroscopy (FT
      IR). Additionally, quantitative analyses were performed by X-Ray Photoelectron
      Spectroscopy (XPS), Energy Dispersive Spectroscopy (EDS), a titration method and
      Thermogravimetric analysis (TGA).

PMID- 29648769
TI  - Oriented and Yellow-Emitting Nano-Phosphor Films of High Transparency Assembled
      from Exfoliated Nanosheets of Layered Rare-Earth Hydroxide (LRH).
AB  - (Y0(.975- x)) Gd(x)Dy(0.025)(2)(OH)(5)NO(3) . nH2O (0 <= x <= 0.975) LRH crystals
      with tens of micron sized laterals have been hydrothermally synthesized by adding
      mineralizer NH(4)NO(3). Smaller LRHs particles, expanded main layer, and shorter
      interlayer distance were found at a higher Gd incorporation. Free anions NO- 3 at
      the interlayer of LRHs have been completely replaced by oleate anions with the
      help of hydrothermal processing, thus weakening the interaction of layers.
      Therefore, tens of micron sized LRH nanosheets can be easily exfoliated from the
      oleate-intercalated LRHs in toluene. Highly [111] oriented and transparent films
      of (Y0975- x Gd x Dy0.025)2O3 (0 <= x <= 0.975), with thicknesses of ~12 nm, have
      been constructed through spin-coating the colloidal suspension of exfoliated
      nanosheets on quartzs, followed by calcination at 800  degrees C. Under
      excitation at 270 nm, the oxide films exhibit typical yellow emission at 576 nm,
      whose intensity shows a clear dependence on Gd3+ concentration. Increasing the Gd
      content from 0 to 97.5 at.% yielded a 450% increase in the yellow emission
      intensity, owing to the energy transfer from Gd(3+) to Dy(3+). Because Gd(3+)
      content has little influence on fluorescence lifetime, fluorescence decay
      analysis yields similar lifetimes of ~1.45 +/- 0.30 ms for all the samples.

PMID- 29648770
TI  - Preparation and Characterization of Ni Nanostructures Coated on the Substrates
      for Glycerol Steam Reforming.
AB  - Glycerol is produced as a major byproduct in a biodiesel production process but
      it has been thrown out as a waste. The glycerol byproduct will increase rapidly
      in amount if the biodiesel commercialization is attainable, so a reforming
      technology is required for glycerol to be used as a high value product. In the
      present study, the catalytic activity of several supported catalysts for glycerol
      steam reforming was measured. The glycerol conversion of Ni foam-supported
      catalyst was higher than that of other supported catalysts such as Al2O3,
      monolith, and SBA-15. The Ni foam-supported catalyst had a good thermal
      dispersion over the catalyst surface because it has higher thermal conductivity
      than other supported catalysts. However, hydrogen selectivity of all support
      catalysts showed the similar result except for SBA-15 supported catalyst on which
      C2H4 and C2H6 were produced.

PMID- 29648771
TI  - Effect of Nickel Coated Multi-Walled Carbon Nanotubes on Electrochemical
      Performance of Lithium-Sulfur Rechargeable Batteries.
AB  - Conventional lithium-sulfur batteries suffer from severe capacity fade, which is
      induced by low electron conductivity and high dissolution of intermediated
      polysulfides. Recent studies have shown the metal (Pt, Au, Ni) as electrocatalyst
      of lithium polysulfides and improved the performance for lithium sulfur
      batteries. In this work, we present the nickel coated multi-walled carbon
      nanotubes (Ni-MWNTs) as additive materials for elemental sulfur positive
      electrodes for lithium-sulfur rechargeable batteries. Compared with MWNTs, the
      obtained Ni-MWNTs/sulfur composite cathode demonstrate a reversible specific
      capacity approaching 545 mAh after 200 cycles at a rate of 0.5C as well as
      improved cycling stability and excellent rate capacity. The improved
      electrochemical performance can be attributed to the fact the MWNTs shows a vital
      role on polysulfides adsorption and nickel has a catalytic effect on the redox
      reactions during charge-discharge process. Meanwhile, the Ni-MWNTs is a good
      electric conductor for sulfur cathode.

PMID- 29648772
TI  - Synthesis and Thermal Analysis of Nano-Aluminum/Fluorinated Polyurethane
      Elastomeric Composites for Structural Energetics.
AB  - Here we describe the synthesis of polyurethane (PU)-based energetic
      nanocomposites loaded with nano-aluminum (n-Al) particles. The energetic
      nanocomposite was prepared by polyurethane reaction of poly(glycidyl azide-co
      tetramethylene glycol) (PGT) prepolymers and IPDI/N-100 isocyanates with
      simultaneous catalyst-free azide-alkyne Click reaction in the presence of n-Al.
      Initial study carried out with various n-Al/fluorinated PGT blends and
      demonstrated the potential of fluorinated PGT prepolymer for an energetic PU
      matrix. Thermal analysis of n-Al/fluorinated PGT-based PU energetic nanocomposite
      was performed using DSC and TGA.

PMID- 29648773
TI  - Electrochemical Properties of Electrodeposited Reduced Graphene Oxide and Carbon
      Nanotubes.
AB  - In this paper, detailed consideration for electrochemical fabrication and
      optimization of different components used in energy storage device. Fabricated
      electrode contained three layers: RGO, CNT, and RGO (RGO/CNT/RGO). GO nanosheets
      were electrochemically modified to RGO utilizing potential scanning from 0 to 
      1.5 V versus silver chloride electrode during electrodeposition. ITO coated glass
      and glassy carbon electrode has been utilized as substrate through this research
      investigation to understand the physical, morphological and structural
      characteristics of the fabricated electrode. AFM and FESEM were performed to
      identify morphological and structural properties of the fabricated electrodes
      components. Besides, electrochemical properties were studied by Cyclic
      Voltammetry which indicates electrode surface area enhanced due to incorporation
      of RGO and CNT. Accordingly, results show the fabricated electrodes could enhance
      performance of energy storage devices. Since unique surface area can boost
      mobility of electrons on top of surface there must be a good trade-off accessible
      among the electrical conductivity and the total ion transportation in structural
      pores.

PMID- 29648774
TI  - Synthesis of a Graphene-Like Nanofilm from Polyacrylonitrile.
AB  - There are various different approaches in synthesizing graphene including
      chemical vapor deposition (CVD) and solid-phase method, where gas or solid type
      carbon source, to be converted into graphene, interacts with transition metals
      such as nickel and copper. When any thin nickel layer coated atop the
      polyacrylonitrile (PAN) film is pyrolyzed at a sufficiently high temperature, it
      is impossible to grow a continuous graphene film with a large area owing to
      dewetting, which has restricted the subsequent utilization in practical
      applications. Herein, we suggest a method to synthesize a continuous graphene
      like nanofilm with a nickel coated thin PAN film through pyrolysis at 750 to 800 
      degrees C in a high-vacuum furnace without a reductive gas flow. The graphene
      like nanofilm obtained was characterized using Raman spectroscopy, Raman mapping,
      field-emission scanning electron microscopy, X-ray photoelectron spectroscopy,
      and field-emission transmission electron microscopy.

PMID- 29648775
TI  - La2O3/Reduced Graphene Oxide Nanocomposite: A Highly Efficient, Reusable
      Heterogeneous Catalyst for the Synthesis of Biologically Important
      Bis(indolyl)methanes Under Solvent Free Conditions.
AB  - Synthesis and characterization of Lanthanum Oxide-reduced graphene oxide
      (La2O3/RGO) nanocomposite and its application as heterogeneous, reusable catalyst
      has been reported in this article. Biologically important molecules
      bis(indolyl)methanes are synthesized in mild reaction condition with excellent
      yield under solvent free condition. Catalyst was reused for four times without
      any significant changes in the yields obtained. Reusability, green synthesis and
      environmentally benign nature makes La2O3/RGO one of the best catalyst for the
      synthesis of biologically important bis(indolyl)methanes.

PMID- 29648777
TI  - Applications of Light-Responsive Systems for Cancer Theranostics.
AB  - Achieving controlled and targeted delivery of chemotherapeutic drugs and other
      therapeutic agents to tumor sites is challenging. Among many stimulus strategies,
      light as a mode of action shows various advantages such as high spatiotemporal
      selectivity, minimal invasiveness and easy operation. Thus, drug delivery systems
      (DDSs) have been designed with the incorporation of various functionalities
      responsive to light as an exogenous stimulus. Early development has focused on
      guiding chemotherapeutic drugs to designated location, followed by the
      utilization of UV irradiation for controlled drug release. Because of the
      disadvantages of UV light such as phototoxicity and limited tissue penetration
      depth, scientists have moved the research focus onto developing nanoparticle
      systems responsive to light in the visible region (400-700 nm), aiming to reduce
      the phototoxicity. In order to enhance the tissue penetration depth, near
      infrared light triggered DDSs become increasingly important. In addition, light
      based advanced systems for fluorescent and photoacoustic imaging, as well as
      photodynamic and photothermal therapy have also been reported. Herein, we
      highlight some of recent developments by applying light-responsive systems in
      cancer theranostics, including light activated drug release, photodynamic and
      photothermal therapy, and bioimaging techniques such as fluorescent and
      photoacoustic imaging. Future prospect of light-mediated cancer treatment is
      discussed at the end of the review. This Spotlights on Applications article aims
      to provide up-to-date information about the rapidly developing field of light
      based cancer theranostics.

PMID- 29648776
TI  - Organogel-Derived Covalent-Noncovalent Hybrid Polymers as Alkali Metal-Ion
      Scavengers for Partial Deionization of Water.
AB  - We show that crown ethers (CEs) 1-5 congeal both polar and nonpolar solvents via
      their self-assembly through weak noncovalent interactions (NCIs) such as CH...O
      and CH...pi interactions. Diisopropylidene-mannitol (6) is a known gelator that
      self-assembles through stronger OH...O H bonding. These two gelators together
      also congeal nonpolar solvents via their individual self-assembly. Gelator 6 self
      assembles swiftly to fibers, which act as templates and attract CE to their
      surface through H bonding and thereby facilitate their self-assembly through weak
      NCI. Polymerization of styrene gels made from CE and 6, followed by the washing
      off of the sacrificial gelator 6, yields robust porous polystyrene-crown ether
      hybrid matrices (PCH), having pore-exposed CEs. These PCHs not only were
      efficient in sequestering alkali metal ions from aqueous solutions but also can
      be recycled. This novel use of organogels for making solid sorbents for metal-ion
      scavenging might be of great interest.

PMID- 29648778
TI  - Metal-Organic Framework-Derived Hollow Carbon Nanocubes for Fast Solid-Phase
      Microextraction of Polycyclic Aromatic Hydrocarbons.
AB  - Developing novel coating materials for fast and sensitive solid-phase
      microextraction (SPME) is highly desired but few are achieved. In this work, a
      new material of metal-organic framework (MOF)-derived hollow carbon nanocubes
      (HCNCs) was prepared as a fiber coating material for SPME. The HCNC-coated fiber
      (denoted as HCNCs-F) exhibited a better enrichment performance than solid carbon
      nanocube (SCNC)-coated fiber (denoted as SCNCs-F) and commercial fibers based on
      the abundant active sites of the hollow structure, hydrophobic interactions, and
      pi-pi interactions. Moreover, because of the reduced mass-transport lengths of
      the hollow mesoporous structure, the HCNCs-F demonstrated a faster mass transfer
      compared with the SCNCs-F. The HCNCs-F was used to determine the six hydrophobic
      polycyclic aromatic hydrocarbons (PAHs) with wide linear ranges (10-2000 ng L-1
      for naphthalene and 5-2000 ng L-1 for the other five analytes), good
      reproducibility (relative standard deviation < 8.8%), and low detection limits
      (0.03-0.70 ng L-1). Finally, the HCNCs-F was successfully applied for the
      determination of PAHs from the real water samples. It can be concluded from the
      results that MOF-derived hollow carbon materials are promising candidates for the
      fast SPME and can be used for practical applications in analytical chemistry.

PMID- 29648779
TI  - The Role of Membrane Curvature in Nanoscale Topography-Induced Intracellular
      Signaling.
AB  - Over the past decade, there has been growing interest in developing biosensors
      and devices with nanoscale and vertical topography. Vertical nanostructures
      induce spontaneous cell engulfment, which enhances the cell-probe coupling
      efficiency and the sensitivity of biosensors. Although local membranes in contact
      with the nanostructures are found to be fully fluidic for lipid and membrane
      protein diffusions, cells appear to actively sense and respond to the surface
      topography presented by vertical nanostructures. For future development of
      biodevices, it is important to understand how cells interact with these
      nanostructures and how their presence modulates cellular function and activities.
      How cells recognize nanoscale surface topography has been an area of active
      research for two decades before the recent biosensor works. Extensive studies
      show that surface topographies in the range of tens to hundreds of nanometers can
      significantly affect cell functions, behaviors, and ultimately the cell fate. For
      example, titanium implants having rough surfaces are better for osteoblast
      attachment and host-implant integration than those with smooth surfaces. At the
      cellular level, nanoscale surface topography has been shown by a large number of
      studies to modulate cell attachment, activity, and differentiation. However, a
      mechanistic understanding of how cells interact and respond to nanoscale
      topographic features is still lacking. In this Account, we focus on some recent
      studies that support a new mechanism that local membrane curvature induced by
      nanoscale topography directly acts as a biochemical signal to induce
      intracellular signaling, which we refer to as the curvature hypothesis. The
      curvature hypothesis proposes that some intracellular proteins can recognize
      membrane curvatures of a certain range at the cell-to-material interface. These
      proteins then recruit and activate downstream components to modulate cell
      signaling and behavior. We discuss current technologies allowing the
      visualization of membrane deformation at the cell membrane-to-substrate interface
      with nanometer precision and demonstrate that vertical nanostructures induce
      local curvatures on the plasma membrane. These local curvatures enhance the
      process of clathrin-mediated endocytosis and affect actin dynamics. We also
      present evidence that vertical nanostructures can induce significant deformation
      of the nuclear membrane, which can affect chromatin distribution and gene
      expression. Finally, we provide a brief perspective on the curvature hypothesis
      and the challenges and opportunities for the design of nanotopography for
      manipulating cell behavior.

PMID- 29648780
TI  - Effective Bioactivity Retention of Low-Concentration Antibodies on HFBI-Modified
      Fluorescence ICTS for Sensitive and Rapid Detection of PSA.
AB  - Nowadays, increasing analytical sensitivity is still a big challenge in
      constructing membrane-based fluorescence immunochromatography test strips
      (FICTS). However, the bioactivity of antibody (Ab) immobilized on the test line
      (T line) of porous nitrocellulose membrane (PNM), which directly influences the
      analytical sensitivity, is less studied. In this work, a novel amphiphilic
      hydrophobin (HFBI) protein was introduced to modify the T line to effectively
      retain the Abs' bioactivity. The results indicated that HFBI could self-assemble
      on the PNM and immobilize the Abs in the "stand-up" orientation. Compared with
      the conventional FICTS, the HFBI-modified FICTS with only 0.2 mg/mL of monoclonal
      Abs on T line enable more accurate quantitative detection and better sensitivity
      (0.06 ng/mL for prostate specific antigen), which is more than 2 orders of
      magnitude lower than that of the conventional FICTS with the same concentration
      of monoclonal Abs on T line. Furthermore, the accuracy of this HFBI-modified
      FICTS was investigated by testing 150 clinical serum samples and the detection
      results were coincident with those by electrochemiluminescence immunoassay. Our
      results provide a novel and promising strategy of Ab immobilization on FICTS for
      near-patient and point-of-care application.

PMID- 29648781
TI  - Polymer-Magnetic Composite Fibers for Remote-Controlled Drug Release.
AB  - An efficient method is reported, for the fabrication of composite microfibers
      that can be magnetically actuated and are biocompatible, targeting controlled
      drug release. Aqueous solutions of polyvinyl alcohol, incorporated with citric
      acid-coated Fe3O4 magnetic nanoparticles (MNPs), are subject to infusion gyration
      to generate 100-300 nm diameter composite fibers, with controllable MNP loading.
      The fibers are stable in polar solvents, such as ethanol, and do not show any
      leaching of MNPs for over 4 weeks. Using acetaminophen as an example, we
      demonstrate that this material is effective in immobilization and triggered
      release of drugs, which is achieved by a moving external magnetic field. The
      remote actuation ability, coupled with biocompatibility and lightweight property,
      renders enormous potential for these fibers to be used as a smart drug release
      agent.

PMID- 29648782
TI  - Van der Waals Coupled Organic Molecules with Monolayer MoS2 for Fast Response
      Photodetectors with Gate-Tunable Responsivity.
AB  - As a direct-band-gap transition metal dichalcogenide (TMD), atomic thin MoS2 has
      attracted extensive attention in photodetection, whereas the hitherto unsolved
      persistent photoconductance (PPC) from the ungoverned charge trapping in devices
      has severely hindered their employment. Herein, we demonstrate the realization of
      ultrafast photoresponse dynamics in monolayer MoS2 by exploiting a charge
      transfer interface based on surface-assembled zinc phthalocyanine (ZnPc)
      molecules. The formed MoS2/ZnPc van der Waals interface is found to favorably
      suppress the PPC phenomenon in MoS2 by instantly separating photogenerated holes
      toward the ZnPc molecules, away from the traps in MoS2 and the dielectric
      interface. The derived MoS2 detector then exhibits significantly improved
      photoresponse speed by more than 3 orders (from over 20 s to less than 8 ms for
      the decay) and a high responsivity of 430 A/W after Al2O3 passivation. It is also
      demonstrated that the device could be further tailored to be 2-10-fold more
      sensitive without severely sacrificing the ultrafast response dynamics using gate
      modulation. The strategy presented here based on surface-assembled organic
      molecules may thus pave the way for realizing high-performance TMD-based
      photodetection with ultrafast speed and high sensitivity.

PMID- 29648783
TI  - Emergence of Fourier's Law of Heat Transport in Quantum Electron Systems.
AB  - The microscopic origins of Fourier's venerable law of thermal transport in
      quantum electron systems has remained somewhat of a mystery, given that previous
      derivations were forced to invoke intrinsic scattering rates far exceeding those
      occurring in real systems. We propose an alternative hypothesis, namely, that
      Fourier's law emerges naturally if many quantum states participate in the
      transport of heat across the system. We test this hypothesis systematically in a
      graphene flake junction and show that the temperature distribution becomes nearly
      classical when the broadening of the individual quantum states of the flake
      exceeds their energetic separation. We develop a thermal resistor network model
      to investigate the scaling of the sample and contact thermal resistances and show
      that the latter is consistent with classical thermal transport theory in the
      limit of large level broadening.

PMID- 29648784
TI  - Design of Mannose-Functionalized Curdlan Nanoparticles for Macrophage-Targeted
      siRNA Delivery.
AB  - 6-Amino-6-deoxy-curdlan is a promising nucleic acid carrier that efficiently
      delivers plasmid DNA as well as short interfering RNA (siRNA) to various cell
      lines. The highly reactive C6-NH2 groups of 6-amino-6-deoxy-curdlan prompt
      conjugation of various side groups including tissue-targeting ligands to enhance
      cell-type-specific nucleic acid delivery to specific cell lines. Herein, to test
      the primary-cell-targeting efficiency of the curdlan derivative, we chemically
      conjugated a macrophage-targeting ligand, mannose, to 6-amino-6-deoxy-curdlan.
      The resulting curdlan derivative (denoted CMI) readily complexed with siRNA and
      formed nanoparticles with a diameter of 50-80 nm. The CMI nanoparticles
      successfully delivered a dye-labeled siRNA to mouse peritoneal macrophages. The
      delivery efficiency was blocked by mannan, a natural ligand for a macrophage
      surface mannose receptor (CD206), but not by zymosan, a ligand for the dectin-1
      receptor, which is also present on the surface of macrophages. Moreover, CMI
      nanoparticles were internalized by macrophages only at 37  degrees C, suggesting
      that the cellular uptake of CMI nanoparticles was energy-dependent. Furthermore,
      CMI nanoparticle efficiently delivered siRNA against tumor necrosis factor alpha
      (TNFalpha) to lipopolysaccharide-stimulated primary mouse peritoneal macrophages.
      In vivo experiments demonstrated that CMI nanoparticles successfully delivered
      siTNFalpha to mouse peritoneal macrophages, liver, and lung and induced
      significant knockdown of the TNFalpha expression at both messenger RNA and
      protein levels. Therefore, our design of CMI may be a promising siRNA carrier for
      targeting CD206-expressing primary cells such as macrophage and dendritic cells.

PMID- 29648785
TI  - An Optical Technique for Mapping Microviscosity Dynamics in Cellular Organelles.
AB  - Microscopic viscosity (microviscosity) is a key determinant of diffusion in the
      cell and defines the rate of biological processes occurring at the nanoscale,
      including enzyme-driven metabolism and protein folding. Here we establish a rotor
      based organelle viscosity imaging (ROVI) methodology that enables real-time
      quantitative mapping of cell microviscosity. This approach uses environment
      sensitive dyes termed molecular rotors, covalently linked to genetically encoded
      probes to provide compartment-specific microviscosity measurements via
      fluorescence lifetime imaging. ROVI visualized spatial and temporal dynamics of
      microviscosity with suborganellar resolution, reporting on a microviscosity
      difference of nearly an order of magnitude between subcellular compartments. In
      the mitochondrial matrix, ROVI revealed several striking findings: a broad
      heterogeneity of microviscosity among individual mitochondria, unparalleled
      resilience to osmotic stress, and real-time changes in microviscosity during
      mitochondrial depolarization. These findings demonstrate the use of ROVI to
      explore the biophysical mechanisms underlying cell biological processes.

PMID- 29648786
TI  - Autonomous Thermal-Oxidative Composition Inversion and Texture Tuning of Liquid
      Metal Surfaces.
AB  - Droplets capture an environment-dictated equilibrium state of a liquid material.
      Equilibrium, however, often necessitates nanoscale interface organization,
      especially with formation of a passivating layer. Herein, we demonstrate that
      this kinetics-driven organization may predispose a material to autonomous thermal
      oxidative composition inversion (TOCI) and texture reconfiguration under
      felicitous choice of trigger. We exploit inherent structural complexity,
      differential reactivity, and metastability of the ultrathin (~0.7-3 nm)
      passivating oxide layer on eutectic gallium-indium (EGaIn, 75.5% Ga, 24.5% In
      w/w) core-shell particles to illustrate this approach to surface engineering. Two
      tiers of texture can be produced after ca. 15 min of heating, with the first
      evolution showing crumpling, while the second is a particulate growth above the
      first uniform texture. The formation of tier 1 texture occurs primarily because
      of diffusion-driven oxide buildup, which, as expected, increases stiffness of the
      oxide layer. The surface of this tier is rich in Ga, akin to the ambient formed
      passivating oxide. Tier 2 occurs at higher temperature because of thermally
      triggered fracture of the now thick and stiff oxide shell. This process leads to
      inversion in composition of the surface oxide due to higher In content on the
      tier 2 features. At higher temperatures (>=800  degrees C), significant changes
      in composition lead to solidification of the remaining material. Volume change
      upon oxidation and solidification leads to a hollow structure with a textured
      surface and faceted core. Controlled thermal treatment of liquid EGaIn therefore
      leads to tunable surface roughness, composition inversion, increased stiffness in
      the oxide shell, or a porous solid structure. We infer that this tunability is
      due to the structure of the passivating oxide layer that is driven by differences
      in reactivity of Ga and In and requisite enrichment of the less reactive
      component at the metal-oxide interface.

PMID- 29648787
TI  - Measuring the Global Substrate Specificity of Mycobacterial Serine Hydrolases
      Using a Library of Fluorogenic Ester Substrates.
AB  - Among the proteins required for lipid metabolism in Mycobacterium tuberculosis
      are a significant number of uncharacterized serine hydrolases, especially lipases
      and esterases. Using a streamlined synthetic method, a library of immolative
      fluorogenic ester substrates was expanded to better represent the natural
      lipidomic diversity of Mycobacterium. This expanded fluorogenic library was then
      used to rapidly characterize the global structure activity relationship (SAR) of
      mycobacterial serine hydrolases in M. smegmatis under different growth
      conditions. Confirmation of fluorogenic substrate activation by mycobacterial
      serine hydrolases was performed using nonspecific serine hydrolase inhibitors and
      reinforced the biological significance of the SAR. The hydrolases responsible for
      the global SAR were then assigned using gel-resolved activity measurements, and
      these assignments were used to rapidly identify the relative substrate
      specificity of previously uncharacterized mycobacterial hydrolases. These
      measurements provide a global SAR of mycobacterial hydrolase activity, a picture
      of cycling hydrolase activity, and a detailed substrate specificity profile for
      previously uncharacterized hydrolases.

PMID- 29648789
TI  - Copper-Catalyzed Oxidative Carbon-Carbon and/or Carbon-Heteroatom Bond Formation
      with O2 or Internal Oxidants.
AB  - Selective oxidation, a fundamental organic transformation of critical importance,
      produces value-added products from simple organic molecules. This process is
      extensively used to incorporate heteroatoms into carbon-based molecules, where
      high-valent metal salts, hypervalent halogen reagents, and peroxides are widely
      used as oxidants. Oxidation reactions are extremely challenging because their
      selectivity is hard to control and/or they form significant quantities of
      unwanted waste derived from the stoichiometric oxidants. Undoubtedly, the
      utilization of green oxidants such as molecular oxygen (O2) or internal oxidants
      provides tunable oxidation abilities and produces no environmentally hazardous
      byproducts. Thus, synthetic chemists have devoted increasing attention to the
      utilization of green oxidants to obtain valuable products. Since the first
      industrial application of noble metal-catalyzed oxidation, i.e., Pd/Cu/O2
      mediated Wacker oxidation, precious metal-catalyzed organic reactions have
      undergone significant development in both the laboratory and industry. However,
      the high cost and considerable toxicity of precious metals compel chemists to
      explore the catalytic activities of earth-abundant, first-row transition metals.
      Copper is abundant, easy to utilize, and relatively insensitive to water and air.
      Controllable access to Cu(0), Cu(I), Cu(II), and Cu(III) oxidation states ensures
      that copper can be applied as a tunable and multifunctional catalyst. Copper
      catalyzed transformations involve single-electron transfer (SET), two-electron
      processes (TEPs) and even the cooperation of SET and TEPs. More importantly, in
      Cu/O2 catalytic systems, ligands, additives, and solvents can tune the oxidation
      state of copper from Cu(I) to Cu(III). As a result, the development of copper
      catalyzed aerobic oxidative reactions is possible and desirable. Progress in
      these synthetic methods will enable breakthroughs in natural product synthesis,
      materials science, and bioorganic chemistry. This Account describes our efforts
      over the last several years to develop copper-catalyzed C-C or C-heteroatom bond
      formation reactions with oxygen or internal oxidants as the oxidant. We primarily
      focused on reaction with simple substrates, including cross-couplings,
      cycloadditions, cyclizations, and condensations. These transformations provide
      convenient and efficient strategies for constructing multiple bonds, such as C
      C/C-O bonds, C-C/C-N bonds, and C-N/C-S bonds, in one pot. Various alkynes,
      furans, benzofurans, lactones, sulfones, thioethers, and nitrogen-containing
      heterocyclic compounds were synthesized with high selectivity and atom economy
      from abundant, commercially available and inexpensive starting materials. These
      methods were successfully applied to the construction of drug molecules and
      skeletons of natural products. Additionally, the designed control experiments and
      serendipitous observations have given us mechanistic insights into copper
      catalyzed green oxidation. Uncovering the activity of copper-catalyzed green
      oxidation involving oxygen and oxime esters has allowed us to extend the scope of
      those green oxidation reactions. We believe that copper-catalyzed green oxidation
      transformations can be made even more eco-friendly and economical in the
      synthesis of valuable compounds.

PMID- 29648788
TI  - Tyr1-psi[( Z)CF?CH]-Gly2 Fluorinated Peptidomimetic Improves Distribution and
      Metabolism Properties of Leu-Enkephalin.
AB  - Opioid peptides are key regulators in cellular and intercellular physiological
      responses, and could be therapeutically useful for modulating several
      pathological conditions. Unfortunately, the use of peptide-based agonists to
      target centrally located opioid receptors is limited by poor physicochemical
      (PC), distribution, metabolic, and pharmacokinetic (DMPK) properties that
      restrict penetration across the blood-brain barrier via passive diffusion. To
      address these problems, the present paper exploits fluorinated peptidomimetics to
      simultaneously modify PC and DMPK properties, thus facilitating entry into the
      central nervous system. As an initial example, the present paper exploited the
      Tyr1-psi[( Z)CF?CH]-Gly2 peptidomimetic to improve PC druglike characteristics
      (computational), plasma and microsomal degradation, and systemic and CNS
      distribution of Leu-enkephalin (Tyr-Gly-Gly-Phe-Leu). Thus, the fluoroalkene
      replacement transformed an instable in vitro tool compound into a stable and
      centrally distributed in vivo probe. In contrast, the Tyr1-psi[CF3CH2-NH]-Gly2
      peptidomimetic decreased stability by accelerating proteolysis at the Gly3-Phe4
      position.

PMID- 29648790
TI  - High-Resolution Inkjet-Printed Oxide Thin-Film Transistors with a Self-Aligned
      Fine Channel Bank Structure.
AB  - A self-aligned inkjet printing process has been developed to construct small
      channel metal oxide (a-IGZO) thin-film transistors (TFTs) with independent bottom
      gates on transparent glass substrates. Poly(methylsilsesquioxane) was used to
      pattern hydrophobic banks on the transparent substrate instead of commonly used
      self-assembled octadecyltrichlorosilane. Photolithographic exposure from backside
      using bottom-gate electrodes as mask formed hydrophilic channel areas for the
      TFTs. IGZO ink was selectively deposited by an inkjet printer in the hydrophilic
      channel region and confined by the hydrophobic bank structure, resulting in the
      precise deposition of semiconductor layers just above the gate electrodes. Inkjet
      printed IGZO TFTs with independent gate electrodes of 10 MUm width have been
      demonstrated, avoiding completely printed channel beyond the broad of the gate
      electrodes. The TFTs showed on/off ratios of 108, maximum mobility of 3.3 cm2 V-1
      s-1, negligible hysteresis, and good uniformity. This method is conductive to
      minimizing the area of printed TFTs so as to the development of high-resolution
      printing displays.

PMID- 29648791
TI  - Anticancer Pyrroloquinazoline LBL1 Targets Nuclear Lamins.
AB  - Target identification of bioactive compounds is critical for understanding their
      mechanism of action. We previously discovered a novel pyrroloquinazoline compound
      LBL1 with significant anticancer activity. However, its molecular targets remain
      to be established. Herein, we developed a clickable photoaffinity probe based on
      LBL1. Using extensive chemical, biochemical, and cellular studies with this probe
      and LBL1, we found that LBL1 targets nuclear lamins, which are type V
      intermediate filament (IF) proteins. Further studies showed that LBL1 binds to
      the coiled-coil domain of lamin A. These results revealed that IF proteins can
      also be targeted with appropriate small molecules besides two other cytoskeletal
      proteins actin filaments and microtubules, providing a novel avenue to
      investigate lamin biology and a novel strategy to develop distinct anticancer
      therapies.

PMID- 29648792
TI  - Color-Changing Microfiber-Based Multifunctional Window Screen for Capture and
      Visualized Monitoring of NH3.
AB  - Air pollution is one of the most serious issues affecting the world today.
      Instead of expensive and energy-intensive air filtering devices, a fiber-based
      transparent air filter coated on a window screen is seen as one of the state-of
      the-art filtration technologies to combat the seriously growing problem,
      delivering the advantages of simplicity, convenience, and high filtering
      efficiency. However, such a window screen is currently limited to particulate
      matter (PM) filtration and ineffective with other air pollutants. Here, we report
      the use of a newfangled type of color-changing fibers, porous Prussian blue
      analogues (CuHCF)/polymer composite microfibers, for transparent window screens
      toward air pollutant filtration. To increase pollution filtration, pores and
      dimples are purposely introduced to the fibers using binary solvent systems
      through a nonsolvent-induced phase separation mechanism. Such composite
      microfibers overcome some of the limitations of those previously used fibers and
      could simultaneously capture PM2.5, PM10, and NH3 with high efficiency. More
      interestingly, a distinct color change is observed upon exposure to air
      pollutants in such window screens, which provides multifunctional capability of
      simultaneous pollutant capture and naked eye screening of the pollutant amount.
      Specifically, in the case of long-term exposure to low-concentration NH3, the
      symbol displayed in such window screens changes from yellow color to brown and
      the coloration rate is directly controlled by the NH3 concentration, which may
      serve as a careful reminder for those people who are repeatedly exposed to low
      concentration ammonia gas (referred to as chronic poisoning). In contrast, after
      short-term exposure to a high concentration of ammonia gas, the yellow symbol
      immediately becomes blackened, which provides timely information about the risk
      of acute ammonia poisoning or even ammonia explosion. Further spectroscopic
      results show that the chromatic behaviors in response to different concentrations
      of NH3 are fundamentally different, which is related to the different locations
      of ammonia in the lattice of CuHCF, either in its interstitial sites or at the
      Fe(CN)6 vacancy sites, largely distinguished by the absence or presence of
      atmospheric moisture.

PMID- 29648793
TI  - Thermophoresis-Controlled Size-Dependent DNA Translocation through an Array of
      Nanopores.
AB  - Large arrays of nanopores can be used for high-throughput biomolecule
      translocation with applications toward size discrimination and sorting at the
      single-molecule level. In this paper, we propose to discriminate DNA length by
      the capture rate of the molecules to an array of relatively large nanopores (50
      130 nm) by introducing a thermal gradient by laser illumination in front of the
      pores balancing the force from an external electric field. Nanopore arrays
      defined by photolithography were batch processed using standard silicon
      technology in combination with electrochemical etching. Parallel translocation of
      single, fluorophore-labeled dsDNA strands is recorded by imaging the array with a
      fast CMOS camera. The experimental data show that the capture rates of DNA
      molecules decrease with increasing DNA length due to the thermophoretic effect of
      the molecules. It is shown that the translocation can be completely turned off
      for the longer molecule using an appropriate bias, thus allowing a size
      discrimination of the DNA translocation through the nanopores. A derived
      analytical model correctly predicts the observed capture rate. Our results
      demonstrate that by combining a thermal and a potential gradient at the
      nanopores, such large nanopore arrays can potentially be used as a low-cost, high
      throughput platform for molecule sensing and sorting.

PMID- 29648794
TI  - Bathochromic Shifts in Rhenium Carbonyl Dyes Induced through Destabilization of
      Occupied Orbitals.
AB  - A series of rhenium diimine carbonyl complexes was prepared and characterized in
      order to examine the influence of axial ligands on electronic structure.
      Systematic substitution of the axial carbonyl and acetonitrile ligands of
      [Re(deeb)(CO)3(NCCH3)]+ (deeb = 4,4'-diethylester-2,2'-bipyridine) with
      trimethylphosphine and chloride, respectively, gives rise to red-shifted
      absorbance features. These bathochromic shifts result from destabilization of the
      occupied d-orbitals involved in metal-to-ligand charge-transfer transitions. Time
      Dependent Density Functional Theory identified the orbitals involved in each
      transition and provided support for the changes in orbital energies induced by
      ligand substitution.

PMID- 29648795
TI  - It Takes Two To Target: A Study in KRAS Dimerization.

PMID- 29648796
TI  - Measurement of Interpeptidic Cu(II) Exchange Rate Constants by Static
      Fluorescence Quenching of Tryptophan.
AB  - The interpeptidic exchange of Cu(II) between biologically relevant peptides like
      Gly-His-Lys (GHK) was measured through proximity static fluorescence quenching of
      a noncoordinating tryptophan residue by Cu(II). The inability to spectrally
      distinguish between starting and final Cu(H-1GHK)+ complexes by the current
      methods was solved by the replacement of noncoordinating lysine for tryptophan in
      the starting complex, Cu(H-1GHW). Because the apoGHW is the only fluorescent
      species, the recovered fluorescence is directly proportional to the
      [Cu(II)]exchanged between GHW and GHK. The apparent second-order rate constants
      of the exchanges from Cu(H-1GHW) to GHK and DAHK are 1.6 (+/-0.2) * 102 and 5.0
      (+/-0.7) * 101 M-1 s-1, respectively. The easy-to-implement kinetic fluorescent
      method described here for Cu(II) interpeptidic exchange can be expanded to other
      biological systems.

PMID- 29648797
TI  - Theoretical Modeling of Singlet Fission.
AB  - Singlet fission is a photophysical reaction in which a singlet excited electronic
      state splits into two spin-triplet states. Singlet fission was discovered more
      than 50 years ago, but the interest in this process has gained a lot of momentum
      in the past decade due to its potential as a way to boost solar cell
      efficiencies. This review presents and discusses the most recent advances with
      respect to the theoretical and computational studies on the singlet fission
      phenomenon. The work revisits important aspects regarding electronic states
      involved in the process, the evaluation of fission rates and interstate
      couplings, the study of the excited state dynamics in singlet fission, and the
      advances in the design and characterization of singlet fission compounds and
      materials such as molecular dimers, polymers, or extended structures. Finally,
      the review tries to pinpoint some aspects that need further improvement and
      proposes future lines of research for theoretical and computational chemists and
      physicists in order to further push the understanding and applicability of
      singlet fission.

PMID- 29648798
TI  - Biosynthesis of Thermoresponsive Magnetic Nanoparticles by Magnetosome Display
      System.
AB  - Thermoresponsive magnetic nanoparticles (MNPs) were synthesized using a
      magnetosome display system. An elastin-like polypeptide decamer of VPGVG (ELP10),
      which is hydrophobic above the transition temperature ( Tt) and can form an
      insoluble aggregation, was immobilized on biogenic MNPs in the magnetotactic
      bacterium, Magnetospirillum magneticum AMB-1. It was suggested that
      hydrophobicity of the MNP surface increased at 60  degrees C compared with 20 
      degrees C by the immobilization of ELP10. Size distribution analysis indicated
      that the immobilization of ELP10 onto MNPs induced the increased hydrophobicity
      with increasing temperatures up to 60  degrees C, promoting aggregation of the
      particles by hydrophobic and magnetic interactions. These results suggest that
      the acceleration of magnetic collection at 60  degrees C was caused by particle
      aggregation promoted by hydrophobic interaction between ELP-MNPs. Furthermore,
      the immobilization of ELP on MNPs gave a quick magnetic collection at 60  degrees
      C by external magnetic field. The thermoresponsive properties will further expand
      the utility of biotechnological applications of biogenic MNPs.

PMID- 29648799
TI  - Comparative Assessment of Active Targeted Redox Sensitive Polymersomes Based on
      pPEGMA-S-S-PLA Diblock Copolymer with Marketed Nanoformulation.
AB  - In the present work, polymersomes based on self-assembled, folate-targeted, redox
      responsive, ATRP-based amphiphilic diblock copolymer poly(polyethylene glycol)-S
      S-polylactide with disulfide linkage were developed for efficient doxorubicin
      (DOX) delivery and compared with marketed DOXIL nanoformulation. The polymersomes
      formulation was optimized by quality by design approach providing monodisperse
      nanostructures of ~110 nm and enhanced DOX loading of ~20%. Polymersomes showed
      excellent stability as per the ICH guidelines over the extended storage period of
      3 months. The in vitro drug release profile confirmed the redox sensitive
      behavior of polymersomes providing ~80% drug release in endosomal pH 5 with 10
      mmol GSH as compared to ~20% release at pH 7.4. The targeted polymersomes
      achieved enhanced cellular internalization in folate receptor overexpressing cell
      lines, MDA-MB-231 and HeLa, providing ~24% higher tumor reduction than DOXIL in
      Ehrlich ascites tumor bearing Swiss albino mice.

PMID- 29648800
TI  - Highly Self-Healable 3D Microsupercapacitor with MXene-Graphene Composite
      Aerogel.
AB  - High-performance microsupercapacitors (MSCs) with three-dimensional (3D)
      structure provide an effective approach to improve the ability of energy storage.
      Because the electrodes with 3D structure are generally easily destroyed under
      mechanical deformation in practical applications, we fabricated a self-healable
      3D MSC consisting of MXene (Ti3C2T x)-graphene (reduced graphene oxide, rGO)
      composite aerogel electrode by wrapping it with a self-healing polyurethane as an
      outer shell. The MXene-rGO composite aerogel combining large specific surface
      area of rGO and high conductivity of the MXene can not only prevent the self
      restacking of the lamella structure but also resist the poor oxidization of MXene
      to a degree. The MSC based on a 3D MXene-rGO aerogel delivers a large area
      specific capacitance of 34.6 mF cm-2 at a scan rate of 1 mV s-1 and an
      outstanding cycling performance with a capacitance retention up to 91% over 15
      000 cycles. The 3D MSC presents an excellent self-healing ability with specific
      capacitance retention of 81.7% after the fifth healing. The preparation of this
      self-healable 3D MSC can provide a method for designing and manufacturing next
      generation long-life multifunctional electronic devices further to meet the
      requirements of sustainable development.

PMID- 29648802
TI  - Quenching Pathways in NaYF4:Er3+,Yb3+ Upconversion Nanocrystals.
AB  - Lanthanide-doped upconversion (UC) phosphors absorb low-energy infrared light and
      convert it into higher-energy visible light. Despite over 10 years of
      development, it has not been possible to synthesize nanocrystals (NCs) with UC
      efficiencies on a par with what can be achieved in bulk materials. To guide the
      design and realization of more efficient UC NCs, a better understanding is
      necessary of the loss pathways competing with UC. Here we study the excited-state
      dynamics of the workhorse UC material beta-NaYF4 co-doped with Yb3+ and Er3+. For
      each of the energy levels involved in infrared-to-visible UC, we measure and
      model the competition between spontaneous emission, energy transfer between
      lanthanide ions, and other decay processes. An important quenching pathway is
      energy transfer to high-energy vibrations of solvent and/or ligand molecules
      surrounding the NCs, as evidenced by the effect of energy resonances between
      electronic transitions of the lanthanide ions and vibrations of the solvent
      molecules. We present a microscopic quantitative model for the quenching dynamics
      in UC NCs. It takes into account cross-relaxation at high lanthanide-doping
      concentration as well as Forster resonance energy transfer from lanthanide
      excited states to vibrational modes of molecules surrounding the UC NCs. Our
      model thereby provides insight in the inert-shell thickness required to prevent
      solvent quenching in NCs. Overall, the strongest contribution to reduced UC
      efficiencies in core-shell NCs comes from quenching of the near-infrared energy
      levels (Er3+: 4I11/2 and Yb3+: 2F5/2), which is likely due to vibrational
      coupling to OH- defects incorporated in the NCs during synthesis.

PMID- 29648801
TI  - The Proline Cycle As a Potential Cancer Therapy Target.
AB  - Interest in how proline contributes to cancer biology is expanding because of the
      emerging role of a novel proline metabolic cycle in cancer cell survival,
      proliferation, and metastasis. Proline biosynthesis and degradation involve the
      shared intermediate Delta1-pyrroline-5-carboxylate (P5C), which forms l-glutamate
      gamma-semialdehyde (GSAL) in a reversible non-enzymatic reaction. Proline is
      synthesized from glutamate or ornithine through GSAL/P5C, which is reduced to
      proline by P5C reductase (PYCR) in a NAD(P)H-dependent reaction. The degradation
      of proline occurs in the mitochondrion and involves two oxidative steps catalyzed
      by proline dehydrogenase (PRODH) and GSAL dehydrogenase (GSALDH). PRODH is a
      flavin-dependent enzyme that couples proline oxidation with reduction of membrane
      bound quinone, while GSALDH catalyzes the NAD+-dependent oxidation of GSAL to
      glutamate. PRODH and PYCR form a metabolic relationship known as the proline-P5C
      cycle, a novel pathway that impacts cellular growth and death pathways. The
      proline-P5C cycle has been implicated in supporting ATP production, protein and
      nucleotide synthesis, anaplerosis, and redox homeostasis in cancer cells. This
      Perspective details the structures and reaction mechanisms of PRODH and PYCR and
      the role of the proline-P5C cycle in cancer metabolism. A major challenge in the
      field is to discover inhibitors that specifically target PRODH and PYCR isoforms
      for use as tools for studying proline metabolism and the functions of the proline
      P5C cycle in cancer. These molecular probes could also serve as lead compounds in
      cancer drug discovery targeting the proline-P5C cycle.

PMID- 29648803
TI  - Flexible Ferroelectric Sensors with Ultrahigh Pressure Sensitivity and Linear
      Response over Exceptionally Broad Pressure Range.
AB  - Flexible pressure sensors with a high sensitivity over a broad linear range can
      simplify wearable sensing systems without additional signal processing for the
      linear output, enabling device miniaturization and low power consumption. Here,
      we demonstrate a flexible ferroelectric sensor with ultrahigh pressure
      sensitivity and linear response over an exceptionally broad pressure range based
      on the material and structural design of ferroelectric composites with a
      multilayer interlocked microdome geometry. Due to the stress concentration
      between interlocked microdome arrays and increased contact area in the multilayer
      design, the flexible ferroelectric sensors could perceive static/dynamic pressure
      with high sensitivity (47.7 kPa-1, 1.3 Pa minimum detection). In addition,
      efficient stress distribution between stacked multilayers enables linear sensing
      over exceptionally broad pressure range (0.0013-353 kPa) with fast response time
      (20 ms) and high reliability over 5000 repetitive cycles even at an extremely
      high pressure of 272 kPa. Our sensor can be used to monitor diverse stimuli from
      a low to a high pressure range including weak gas flow, acoustic sound, wrist
      pulse pressure, respiration, and foot pressure with a single device.

PMID- 29648804
TI  - Computation-Assisted Nanopore Detection of Thorium Ions.
AB  - Thorium is a well-known radioactive and chemically toxic contaminant in the
      environment. The continuous exposure to thorium may cause an increased risk of
      developing lung and liver diseases as well as lung, pancreas, and bone cancer.
      Due to its use in nuclear industry and other industrial applications, thorium may
      be accidentally released to the environment from its mining and processing
      plants. In this work, we developed a rapid, real-time, and label-free nanopore
      sensor for Th4+ detection by using an aspartic acid containing peptide as a
      chelating agent and tuning the electrolyte solution pH to control the net charges
      of the peptide ligand and its metal ion complex. The method is highly sensitive
      with a detection limit of 0.45 nM. Furthermore, the sensor is selective: other
      metal ions (e.g., UO22+, Pb2+, Cu2+, Ni2+, Hg2+, Zn2+, As3+, Mg2+, and Ca2+) with
      concentrations of up to 3 orders of magnitude greater than that of Th4+ would not
      interfere with Th4+detection. In addition, simulated water samples were
      successfully analyzed. Our developed computation-assisted sensing strategy should
      find useful applications in the development of nanopore sensors for other metal
      ions.

PMID- 29648805
TI  - Land Use Intensity-Specific Global Characterization Factors to Assess Product
      Biodiversity Footprints.
AB  - The UNEP-SETAC life cycle initiative recently recommended use of the countryside
      species-area relationship (SAR) model to calculate the characterization factors
      (CFs; potential species loss per m2) for projecting the biodiversity impact of
      land use associated with a products' life cycle. However, CFs based on this
      approach are to date available for only six broad land use types without
      differentiating between their management intensities and have large uncertainties
      that limit their practical applicability. Here we derive updated CFs for
      projecting potential species losses of five taxa resulting from five broad land
      use types (managed forests, plantations, pasture, cropland, urban) under three
      intensity levels (minimal, light, and intense use) in each of the 804 terrestrial
      ecoregions. We utilize recent global land use intensity maps and International
      Union for Conservation of Nature (IUCN) habitat classification scheme to
      parametrize the SAR model. As a case study, we compare the biodiversity impacts
      of 1 m3 of wood produced under four different forest management regimes in India
      and demonstrate that the new land use intensity-specific CFs have smaller
      uncertainty intervals and are able to discern the impacts of intensively managed
      land uses from the low intensity regimes, which has not been possible through
      previous CFs.

PMID- 29648806
TI  - Strategy for Stabilization of CutA1 Proteins Due to Ion-Ion Interactions at
      Temperatures of over 100  degrees C.
AB  - In order to elucidate the contribution of charged residues to protein
      stabilization at temperatures of over 100  degrees C, we constructed many mutants
      of the CutA1 protein ( EcCutA1) from Escherichia coli. The goal was to see if one
      can achieve the same stability as for a CutA1 from hyperthermophile Pyrococcus
      horikoshii that has the denaturation temperature near 150  degrees C. The
      hydrophobic mutant of EcCutA1 ( Ec0VV) with denaturation temperature ( Td) of
      113.2  degrees C was used as a template for mutations. The highest Td of Ec0VV
      mutants substituted by a single charged residue was 118.4  degrees C. Multiple
      ion mutants were also constructed by combination of single mutants and found to
      have an increased thermostability. The highest stability of multiple mutants was
      a mutant substituted by nine charged residues that had a Td of 142.2  degrees C.
      To evaluate the energy of ion-ion interactions of mutant proteins, we used the
      structural ensemble obtained by a molecular dynamics simulation at 300 K. The Td
      of ionic mutants linearly increases with the increments of the computed energy of
      ion-ion interactions for ionic mutant proteins even up to the temperatures near
      140  degrees C, suggesting that ion-ion interactions cumulatively contribute to
      the stabilization of a protein at high temperatures.

PMID- 29648807
TI  - Density of Grafted Chains in Thioglycerol-Capped CdS Quantum Dots Determines
      Their Interaction with Aluminum(III) in Water.
AB  - We aimed to quantify the interaction of water-soluble-functionalized CdS quantum
      dots (QDs) with metal cations from their composition and physical properties.
      From the diameter of thioglycerol-capped nanoparticles (TG-CdS QDs) measured by
      electronic microscopy ( D = 12.3 +/- 0.3 nm), we calculated the molecular mass of
      the individual particle MAQD = (3 +/- 0.5) * 106 g.mol-1 and its molar absorption
      coefficient epsilon450 = 21 * 106 M-1.cm-1. We built a three-dimensional model of
      the TG-CdS QDs in agreement with the structural data, which allowed us to
      quantify the number of thioglycerol grafted chains to ~2000 per QD. This value
      fully matches the saturation binding curve of Al3+ cations interacting with TG
      CdS QDs. The reaction occurred with a slow association rate ( kon = 2.1 * 103 M
      1.s-1), as expected for heavy QDs. The photophysical properties of the
      functionalized QDs were studied using an absolute QD concentration of 7 nM, which
      allowed us to investigate the interaction with 14 metallic cations in water. The
      fluorescence intensity of TG-CdS QDs could be quenched only in the presence of
      Al3+ ions in the range 0.2-10 MUM but not with other cations and was not observed
      with other kinds of grafting chains.

PMID- 29648808
TI  - Enhanced Uranium Immobilization by Phosphate Amendment under Variable Geochemical
      and Flow Conditions: Insights from Reactive Transport Modeling.
AB  - Phosphate amendment has shown promise for enhancing uranium immobilization. The
      mechanism of the enhancement, however, has remained unclear with contrasting
      observations under variable environmental conditions. A dual-domain reactive
      transport model is developed here with constraints from batch and column
      experimental data to understand the mechanisms and to explore the effectiveness
      of enhanced U(VI) immobilization under variable geochemical and flow conditions.
      Modeling results indicate that under low U(VI) conditions in natural waters,
      phosphate addition promotes U(VI) immobilization through the formation of U(VI)
      phosphate ternary surface complexes and the precipitation of calcium phosphate,
      both decreasing the concentrations of mobile U-Ca-CO3 aqueous complexes. This
      contrasts with previous hypotheses attributing the immobilization enhancement to
      U(VI)-phosphate precipitation under experimental conditions with high U(VI).
      Sensitivity analysis shows that phosphate is effective under relatively low Ca
      (<0.1 mM) and total inorganic carbon (TIC) (<0.5 mM) conditions, where >60% of
      U(VI) still remains on sediments after 113 residence times of flushing with low
      phosphate solutions (<0.1 mM). Under high Ca or TIC conditions, a similar level
      of U(VI) immobilization can be achieved only when the phosphate concentration is
      higher than Ca or TIC concentrations. Compared to the strong geochemical effects,
      flow conditions have relatively limited impacts on U(VI) immobilization. These
      results explain contrasting field observations on the effectiveness of phosphate
      amendment and offer capabilities to extrapolate observations to other
      environmental conditions.

PMID- 29648810
TI  - FeCl2-Catalyzed Decarboxylative Radical Alkylation/Cyclization of Cinnamamides:
      Access to Dihydroquinolinone and Pyrrolo[1,2- a]indole Analogues.
AB  - A simple and unified method for the synthesis of alkylated dihydroquinolinone and
      pyrrolo[1,2- a]indole derivatives in moderate to high yields (up to 91%) with
      excellent diastereoselectivity (>20:1 dr) was developed. The inexpensive
      FeCl2.4H2O works as catalyst, and easily prepared peresters (or peroxides) from
      aliphatic acids act as alkylating reagents and single electron oxidants. This
      environmentally friendly reaction proceeds via an FeCl2-catalyzed alkyl radical
      cascade addition/cyclization fashion.

PMID- 29648809
TI  - Iron(MCP) Complexes Catalyze Aziridination with Olefins As Limiting Reagents.
AB  - Herein described are the first efficient nitrogen-atom transfer reactions
      mediated by iron N, N'-dimethyl- N, N'-bis(2-pyridinylmethyl)cyclohexane-1,2
      diamine- (MCP-) and 2-({1-[(pyridin-2-ylmethyl)pyrrolidin-2-yl]pyrrolidin-1
      yl}methyl)pyridine-type (PDP-type) complexes. These catalysts affect styrene
      aziridination under mild conditions based on a limiting quantity of olefin
      substrate.

PMID- 29648811
TI  - Combating Drug-Resistant Fungi with Novel Imperfectly Amphipathic Palindromic
      Peptides.
AB  - Antimicrobial peptides are an important weapon against invading pathogens and are
      potential candidates as novel antibacterial agents, but their antifungal
      activities are not fully developed. In this study, a set of imperfectly
      amphipathic peptides was developed based on the imperfectly amphipathic
      palindromic structure R n(XRXXXRX)R n ( n = 1, 2; X represents L, I, F, or W),
      and the engineered peptides exhibited high antimicrobial activities against all
      fungi and bacteria tested (including fluconazole-resistant Candida albicans),
      with geometric mean (GM) MICs ranging from 2.2 to 6.62 MUM. Of such peptides, 13
      (I6) (RRIRIIIRIRR-NH2) that was Ile rich in its hydrophobic face had the highest
      antifungal activity (GMfungi = 1.64 MUM) while showing low toxicity and high salt
      and serum tolerance. It also had dramatic LPS-neutralizing propensity and a
      potent membrane-disruptive mechanism against microbial cells. In summary, these
      findings were useful for short AMPs design to combat the growing threat of drug
      resistant fungal and bacterial infections.

PMID- 29648812
TI  - Minimum Energy Paths and Transition States by Curve Optimization.
AB  - Transition states and minimum energy paths are essential to understand and
      predict chemical reactivity. Double-ended methods represent a standard approach
      for their determination. We introduce a new double-ended method that optimizes
      reaction paths described by curves. Unlike other methods, our approach optimizes
      the curve parameters rather than distinct structures along the path. With
      molecular paths represented as continuous curves, the optimization can benefit
      from the advantages of an integral-based formulation. We call this approach
      ReaDuct and demonstrate its applicability for molecular paths parametrized by B
      spline curves.

PMID- 29648814
TI  - Preparation of Bioactive Polysaccharide Nanoparticles with Enhanced Radical
      Scavenging Activity and Antimicrobial Activity.
AB  - Because of their biocompatibility and biodegradability in vivo, natural
      polysaccharides are effective nanocarriers for delivery of active ingredients or
      drugs. Moreover, bioactive polysaccharides, such as tea, Ganoderma lucidum, and
      Momordica charantia polysaccharides (TP, GLP, and MCP), have antibacterial,
      antioxidant, antitumor, and antiviral properties. In this study, tea, Ganoderma
      lucidum, and Momordica charantia polysaccharide nanoparticles (TP-NPs, GLP-NPs,
      and MCP-NPs) were prepared via the nanoprecipitation approach. When the ethanol
      to water ratio was 10:1, the diameter of the spherical polysaccharide
      nanoparticles was the smallest, and the mean particle size of the TP-NPs, GLP
      NPs, and MCP-NPs was 99 +/- 15, 95 +/- 7, and 141 +/- 9 nm, respectively. When
      exposed to heat, increased ionic strength and pH levels, the nanoparticles
      exhibited superior stability and higher activity than the corresponding
      polysaccharides. In physiological conditions (pH 7.4), the nanoparticles
      underwent different protein adsorption capacities in the following order: MCP
      NPs> TP-NPs> GLP-NPs. Moreover, the 2,2-diphenyl-1-picrylhydrazyl (DPPH),
      hydroxyl radical, and superoxide anion radical scavenging rates of the
      nanoparticles were increased by 9-25% as compared to the corresponding
      polysaccharides. Compared to the bioactive polysaccharides, the nanoparticles
      enhanced antimicrobial efficacy markedly and exhibited long-acting antibacterial
      activity.

PMID- 29648813
TI  - Small Molecule Neuropilin-1 Antagonists Combine Antiangiogenic and Antitumor
      Activity with Immune Modulation through Reduction of Transforming Growth Factor
      Beta (TGFbeta) Production in Regulatory T-Cells.
AB  - We report the design, synthesis, and biological evaluation of some potent small
      molecule neuropilin-1 (NRP1) antagonists. NRP1 is implicated in the immune
      response to tumors, particularly in Treg cell fragility, required for PD1
      checkpoint blockade. The design of these compounds was based on a previously
      identified compound EG00229. The design of these molecules was informed and
      supported by X-ray crystal structures. Compound 1 (EG01377) was identified as
      having properties suitable for further investigation. Compound 1 was then tested
      in several in vitro assays and was shown to have antiangiogenic, antimigratory,
      and antitumor effects. Remarkably, 1 was shown to be selective for NRP1 over the
      closely related protein NRP2. In purified Nrp1+, FoxP3+, and CD25+ populations of
      Tregs from mice, 1 was able to block a glioma-conditioned medium-induced increase
      in TGFbeta production. This comprehensive characterization of a small-molecule
      NRP1 antagonist provides the basis for future in vivo studies.

PMID- 29648816
TI  - The Pharmacophore Network: A Computational Method for Exploring Structure
      Activity Relationships from a Large Chemical Data Set.
AB  - Historically, structure-activity relationship (SAR) analysis has focused on small
      sets of molecules, but in recent years, there has been increasing efforts to
      analyze the growing amount of data stored in public databases like ChEMBL. The
      pharmacophore network introduced herein is dedicated to the organization of a set
      of pharmacophores automatically discovered from a large data set of molecules.
      The network navigation allows to derive essential tasks of a drug discovery
      process, including the study of the relations between different chemical series,
      the analysis of the influence of additional chemical features on the compounds'
      activity, and the identification of diverse binding modes. This paper describes
      the method used to construct the pharmacophore network, and a case study dealing
      with BCR-ABL exemplifies its usage for large-scale SAR analysis. Thanks to a
      benchmarking study, we also demonstrate that the selection of a subset of
      representative pharmacophores can be used to conduct classification tasks.

PMID- 29648815
TI  - Peptidomimetic-Based Multidomain Targeting Offers Critical Evaluation of Abeta
      Structure and Toxic Function.
AB  - The prevailing hypothesis stipulates that the preamyloid oligomers of Abeta are
      the main culprits associated with the onset and progression of Alzheimer's
      disease (AD), which has prompted efforts to search for therapeutic agents with
      the ability to inhibit Abeta oligomerization and amyloidogenesis. However,
      clinical progress is impeded by the limited structural information about the
      neurotoxic oligomers. To address this issue, we have adopted a synthetic
      approach, where a library of oligopyridylamide-based small molecules was tested
      against various microscopic events implicated in the self-assembly of Abeta. Two
      oligopyridylamides bind to different domains of Abeta and affect distinct
      microscopic events in Abeta self-assembly. The study lays the foundations for a
      dual recognition strategy to simultaneously target different domains of Abeta for
      further improvement in antiamyloidogenic activity. The data demonstrate that one
      of the most effective oligopyridylamides forms a high affinity complex with
      Abeta, which sustains the compound's activity in cellular milieu. The
      oligopyridylamide was able to rescue cells when introduced 24 h after the
      incubation of Abeta. The rescue of Abeta toxicity is potentially a consequence of
      the colocalization of the oligopyridylamide with Abeta. The synthetic tools
      utilized here provide a straightforward strategic framework to identify a range
      of potent antagonists of Abeta-mediated toxic functions. This approach could be a
      powerful route to the design of candidate drugs for various amyloid diseases that
      have so far proven to be "untargetable".

PMID- 29648817
TI  - Tight-Binding Inhibition of Human Monoamine Oxidase B by Chromone Analogs: A
      Kinetic, Crystallographic, and Biological Analysis.
AB  - Monoamine oxidase B (MAO-B) is a validated drug target for Parkinson's disease.
      Chromone derivatives were identified as novel potent and reversible MAO-B
      inhibitors, and herewith we report on a crystallographic and biochemical analysis
      to investigate their inhibition mechanism. The crystal structures of human MAO-B
      in complex with three chromone analogs bearing different substituents on the
      exocyclic aromatic ring (determined at 1.6-1.8 A resolution) showed that they all
      bind in the active site cavity of the protein with the chromone moiety located in
      front of the FAD cofactor. These inhibitors form two hydrogen bonds with Tyr435
      and Cys172 and perfectly fit the hydrophobic flat active site of human MAO-B.
      This is reflected in their tight-binding mechanism of inhibition with Ki values
      of 55, 17, and 31 nM for N-(3',4'-dimethylphenyl)-4-oxo-4 H-chromene-3
      carboxamide (1), N-(3'-chlorophenyl)-4-oxo-4 H-chromene-3-carboxamide (2), and N
      (3'-fluorophenyl)-4-oxo-4 H-chromene-3-carboxamide (3), respectively. These
      compounds were also 1000-fold more effective than l-deprenyl in reducing the
      cellular levels of reactive oxygen species (ROS).

PMID- 29648818
TI  - Imidazole Alkaloids and Their Zinc Complexes from the Calcareous Marine Sponge
      Leucetta chagosensis.
AB  - Five new imidazole derivatives (1-5), together with eight related known
      alkaloids, were isolated from a calcareous marine sponge, Leucetta chagosensis,
      collected from the South China Sea. Their structures were fully characterized by
      spectroscopic methods. Structurally, 1 possesses an unusual skeleton featuring
      imidazole and oxazolone rings linked via a nitrogen atom, whereas 2 bears an
      intriguing guanylurea-substituted imidazole ring. Compounds 4 and 5 were
      identified as zinc complexes; they represent the metal complex analogues of
      naamidine J (6) and pyronaamidine (7), respectively. Among the isolated
      compounds, 2 and 5 showed significant inhibitory activities toward the LPS
      induced production of IL-6 in the human acute monocytic leukemia cell line THP-1,
      and 7 displayed cytotoxicity against MCF-7, PC9, A549, and breast cancer stem
      cells (MCF-7-Oct4-GFP) with IC50 values of 5.2, 5.6, 7.8, and 10 MUM,
      respectively.

PMID- 29648820
TI  - Facile C-H Bond Metathesis Mediated by a Stannylene.
AB  - The diarylstannylene, :Sn(Ar iPr4)2 (Ar iPr4 = C6H3-2,6-(C6H3-2,6- iPr2)2),
      undergoes C-H metathesis with toluene, m-xylene, or mesitylene in solutions of
      these solvents at 80  degrees C. The products, [Ar iPr4Sn(CH2Ar)]2 (Aryl=C6H5
      (1a), C6H4-3-Me (1b), C6H3-3,5-Me2(1c)) were characterized via 1H, 13C and 119Sn
      NMR, UV-vis and IR spectroscopy, and by X-ray crystallography for 1a and 1b. A
      stoichiometric amount of the arene, Ar iPr4H, was also produced in these
      reactions. The use of EPR spectroscopy indicated the presence of a new type of
      one-coordinate, tin-centered radical, :SnAr iPr4, resulting from Sn-C bond
      cleavage in Sn(Ar iPr4)2.

PMID- 29648821
TI  - One-Pot Synthesis of Trifluoromethylated Quinazolin-4(3 H)-ones with
      Trifluoroacetic Acid as CF3 Source.
AB  - A novel and convenient one-pot sequential cascade method for the preparation of 2
      trifluoromethylquinazolin-4(3 H)-ones is described. Trifluoroacetic acid (TFA)
      was employed as inexpensive and readily available CF3 source, which in the
      presence of T3P was condensed with a variety of anthranilic acids and amines to
      provide the products in up to 75% yield. The protocol was proved to be robust on
      80 g scale, and the synthetic versatility of the prepared quinazolinon-4-ones was
      demonstrated by derivatization to further useful building blocks.

PMID- 29648822
TI  - Effect of Epichloe gansuensis Endophyte on the Nitrogen Metabolism, Nitrogen Use
      Efficiency, and Stoichiometry of Achnatherum inebrians under Nitrogen Limitation.
AB  - The systemic fungal endophyte of the grass Achnatherum inebrians, Epichloe
      gansuensis, has important roles in enhancing resistance to biotic and abiotic
      stresses. In this work, we first evaluated the effects of E. gansuensis on
      nitrogen metabolism, nitrogen use efficiency, and stoichiometry of A. inebrians
      under varying nitrogen concentrations. The results demonstrated that E.
      gansuensis significantly improved the growth of A. inebrians under low nitrogen
      conditions. The fresh and dry weights, nitrogen reductase, nitrite reductase, and
      glutamine synthetase activity, NO3-, NH4+, N, and P content, and also the total N
      accumulation, N utilization efficiency, and N uptake efficiency were all higher
      in leaves of A. inebrians with E. ganusensis (E+) plants than A. inebrians plants
      without this endophyte (E-) under low nitrogen availability. In conclusion, E.
      gansuensis has positive effects on improving the growth of A. inebrians under low
      nitrogen conditions by modulating the enzymes of nitrogen metabolism and
      enhancing nitrogen use efficiency.

PMID- 29648823
TI  - Three-Component Site-Selective Synthesis of Highly Substituted 5 H-Chromeno-[4,3-
      b]pyridines.
AB  - An efficient and concise one-pot procedure was developed based on a cascade
      reaction of 3-formylchromones 1 and different types of 1,1-enediamines (EDAMs) 2
      with different alcohols or amines 3 by a site-selective synthesis of 5 H
      chromeno[4,3- b]pyridines in an environmentally friendly solvent. This protocol
      is especially suitable for the efficient and rapid parallel synthesis of 5 H
      chromeno[4,3- b]pyridine compounds. It also has some advantages, such as
      convenience of operation, short reaction times, use of a green solvent, and ease
      of purification by washing the crude products with ethanol.

PMID- 29648824
TI  - Impact of Interfacial Composition on Lipid and Protein Co-Oxidation in Oil-in
      Water Emulsions Containing Mixed Emulisifers.
AB  - The impact of interfacial composition on lipid and protein co-oxidation in oil-in
      water emulsions containing a mixture of proteins and surfactants was
      investigated. The emulsions consisted of 5% v/v walnut oil, 0.5% w/v whey protein
      isolate (WPI), and 0 to 0.4% w/v Tween 20 (pH 3 and pH 7). The protein surface
      load, magnitude of the xi-potential, and mean particle diameter of the emulsions
      decreased as the Tween 20 concentration was increased, indicating the whey
      proteins were displaced by this nonionic surfactant. The whey proteins were
      displaced from the lipid droplet surfaces more readily at pH 3 than at pH 7,
      which may have been due to differences in the conformation or interactions of the
      proteins at the droplet surfaces at different pH values. Emulsions stabilized by
      whey proteins alone had relatively low lipid oxidation rates when incubated in
      the dark at 45  degrees C for up to 8 days, as determined by measuring lipid
      hydroperoxides and 2-thiobarbituric acid-reactive substances (TBARS). Conversely,
      the whey proteins themselves were rapidly oxidized, as shown by carbonyl
      formation, intrinsic fluorescence, sulfhydryl group loss, and electrophoresis
      measurements. Displacement of whey proteins from the interface by Tween 20
      reduced protein oxidation but promoted lipid oxidation. These results indicated
      that the adsorbed proteins were more prone to oxidation than the nonadsorbed
      proteins, and therefore, they could act as better antioxidants. Protein oxidation
      was faster, while lipid oxidation was slower at pH 3 than at pH 7, which was
      attributed to a higher antioxidant activity of whey proteins under acidic
      conditions. These results highlight the importance of interfacial composition and
      solution pH on the oxidative stability of emulsions containing mixed emulsifiers.

PMID- 29648825
TI  - Rational Drug Design of Topically Administered Caspase 1 Inhibitors for the
      Treatment of Inflammatory Acne.
AB  - The use of an interleukin beta antibody is currently being investigated in the
      clinic for the treatment of acne, a dermatological disorder affecting 650M
      persons globally. Inhibiting the protease responsible for the cleavage of
      inactive pro-IL1beta into active IL-1beta, caspase-1, could be an alternative
      small molecule approach. This report describes the discovery of uracil 20, a
      potent (38 nM in THP1 cells assay) caspase-1 inhibitor for the topical treatment
      of inflammatory acne. The uracil series was designed according to a published
      caspase-1 pharmacophore model involving a reactive warhead in P1 for covalent
      reversible inhibition and an aryl moiety in P4 for selectivity against the
      apoptotic caspases. Reversibility was assessed in an enzymatic dilution assay or
      by using different substrate concentrations. In addition to classical structure
      activity-relationship exploration, topical administration challenges such as
      phototoxicity, organic and aqueous solubility, chemical stability in solution,
      and skin metabolic stability are discussed and successfully resolved.

PMID- 29648826
TI  - N-Substituted Prodrugs of Mebendazole Provide Improved Aqueous Solubility and
      Oral Bioavailability in Mice and Dogs.
AB  - Mebendazole (MBZ) was developed as a broad-spectrum anthelmintic but has recently
      shown efficacy as an anticancer agent. The use of MBZ for cancer, however, is
      challenging due to its poor solubility leading to poor bioavailability. Herein,
      we developed a prodrug approach with various N-linked promoieties including
      acyloxymethyl, aminoacyloxymethyl, and substituted phosphonooxymethyl in attempt
      to improve these characteristics. Compound 12, containing an
      (((((isopropoxycarbonyl)oxy)methoxy)phosphoryl)oxy)methyl promoiety, showed a >10
      000-fold improvement in aqueous solubility. When evaluated in mice, 12 displayed
      a 2.2-fold higher plasma AUC0- t and a 1.7-fold improvement in brain AUC0- t with
      a calculated oral bioavailability of 52%, as compared to 24% for MBZ-polymorph C
      (MBZ-C), the most bioavailable polymorph. In dogs, 12 showed a 3.8-fold higher
      plasma AUC0- t with oral bioavailability of 41% compared to 11% for MBZ-C. In
      summary, we have identified a prodrug of MBZ with better physicochemical
      properties and enhanced bioavailability in both mice and dog.

PMID- 29648827
TI  - A Concentration-Dependent Insulin Immobilization Behavior of Alkyl-Modified
      Silica Vesicles: The Impact of Alkyl Chain Length.
AB  - The insulin immobilization behaviors of silica vesicles (SV) before and after
      modification with hydrophobic alkyl -C8 and -C18 groups have been studied and
      correlated to the grafted alkyl chain length. In order to minimize the influence
      from the other structural parameters, monolayered -C8 or -C18 groups are grafted
      onto SV with controlled density. The insulin immobilization capacity of SV is
      dependent on the initial insulin concentrations (IIC). At high IIC (2.6-3.0
      mg/mL), the trend of insulin immobilization capacity of SV is SV-OH > SV-C8 > SV
      C18, which is determined mainly by the surface area of SV. At medium IIC (0.6-1.9
      mg/mL), the trend changes to SV-C8 >= SV-C18 > SV-OH as both the surface area and
      alkyl chain length contribute to the insulin immobilization. At an extremely low
      IIC, the hydrophobic-hydrophobic interaction between the alkyl group and insulin
      molecules plays the most significant role. Consequently, SV-C18 with longer alkyl
      groups and the highest hydrophobicity show the best insulin enrichment
      performance compared to SV-C8 and SV-OH, as evidenced by an insulin detection
      limit of 0.001 ng/mL in phosphate buffered saline (PBS) and 0.05 ng/mL in
      artficial urine determined by mass spectrometry (MS).

PMID- 29648828
TI  - Photoactive Molecular Dyads [Ru(bpy)3-M(ttpy)2] n+ on Gold (M = Co(III), Zn(II)):
      Characterization, Intrawire Electron Transfer, and Photoelectric Conversion.
AB  - We propose in this work a stepwise approach to construct photoelectrodes. This
      takes advantage of the self-assembly interactions between thiol with a gold
      surface and terpyridine ligands with first-row transition metals. Here, a
      [Ru(bpy)3]2+ photosensitive center bearing a free terpyridine group has been used
      to construct two linear dyads on gold (Au/[ZnII-RuII]4+ and Au/[CoIII-RuII]5+).
      The stepwise construction was characterized by electrochemistry, quartz crystal
      microbalance, and atomic force microscopy imaging. The results show that the
      dyads behave as rigid layers and are inhomogeneously distributed on the surface.
      The surface coverages are estimated to be in the order of 10-11 mol cm-2. The
      kinetics of the heterogeneous electron transfer is determined on modified gold
      ball microelectrodes using Laviron's formula. The oxidation rates of the terminal
      Ru(II) subunits are estimated to be 700 and 2300 s-1 for Au/[ZnII-RuII]4+ and
      Au/[CoIII-RuII]5+, respectively. In the latter case, the rate is limited by the
      kinetics of electron transfer between an intermediate Co(II) center and the gold
      surface. For Au/[ZnII-RuII]4+, the Zn-bis-terpyridine center is not involved in
      the electron-transfer process and the oxidation of the Ru(II) subunit occurs
      through a superexchange process. In the presence of a tertiary amine in solution,
      the electrodes at a bias of 0.12 V behave as photoanodes when subjected to
      visible light irradiation. The magnitude of the photocurrent is around 10 MUA cm
      2 for Au/[CoIII-RuII]5+ and 5 MUA cm-2 for Au/[ZnII-RuII]4+, proving the
      importance of an electron relay on the photon-to-current conversion. The results
      suggest an efficient conversion for Au/[CoIII-RuII]5+, since each bound dyad,
      once excited, injects an electron around 10 times per second.

PMID- 29648829
TI  - Selective Permeation through One-Atom-Thick Nanoporous Carbon Membranes: Theory
      Reveals Excellent Design Strategies!
AB  - Research on the permeation of various species through one-atom-thick nanoporous
      carbon membranes has gained an unprecedented importance in the past decade,
      thanks to the development of numerous theoretical design strategies for a
      plethora of applications ranging from gas separation, water desalination, isotope
      separation, and chiral separation, to DNA sequencing. Although some of the recent
      experiments have demonstrated successful performance of such carbon membranes in
      sieving, many of the suggested applications are yet to be realized in
      experiments. This review aims to draw the attention of the theoretical as well as
      the experimental researchers working on two-dimensional carbon materials toward
      the recent theoretical developments probing the permeation of various species
      such as atoms, ions, small molecules, and biopolymers like DNA through carbon
      frameworks like graphynes, graphdiyne, graphenylenes, and various forms of
      nanoporous graphene, including graphene crown ethers. The underlying guiding
      principles toward the design of carbon-based membranes for nanofiltration are
      established using estimates of the adsorption energies, barrier heights for
      permeation, rates of permeation, selectivities, permeances, etc. The crucial
      roles of tunneling, temperature effects, chemical functionalities, and dynamical
      aspects of the nanopores are also highlighted, paving the way to a comprehensive
      description of the theoretical design strategies for tailoring the applicability
      of novel nanoporous carbon membranes in sieving and related aspects.

PMID- 29648830
TI  - Efficient Nitrogen Fixation via a Redox-Flexible Single-Iron Site with Reverse
      Dative Iron -> Boron sigma Bonding.
AB  - Model systems of the FeMo cofactor of nitrogenase have been explored extensively
      in catalysis to gain insights into their ability for nitrogen fixation that is of
      vital importance to the human society. Here we investigate the trigonal pyramidal
      borane-ligand Fe complex by first-principles calculations, and find that the
      variation of oxidation state of Fe along the reaction path correlates with that
      of the reverse-dative Fe -> B bonding. The redox-flexibility of the reverse
      dative Fe -> B bonding helps to provide an electron reservoir that buffers and
      stabilizes the evolution of Fe oxidation state, which is essential for forming
      the key intermediates of N2 activation. Our work provides insights for
      understanding and optimizing homogeneous and surface single-atom catalysts with
      reverse-dative donating ligands for efficient dinitrogen fixation. The extension
      of this kind of molecular catalytic active center to heterogeneous catalysts with
      surface single-clusters is also discussed.

PMID- 29648831
TI  - Molecular Mechanism Behind the Resistance of the G1202R-Mutated Anaplastic
      Lymphoma Kinase to the Approved Drug Ceritinib.
AB  - Anaplastic lymphoma kinase (ALK) has been regarded as an essential target for the
      treatment of nonsmall cell lung cancer (NSCLC). However, the emergence of the
      G1202R solvent front mutation that confers resistance to the drugs was reported
      for the first as well as the second generation ALK inhibitors. It was thought
      that the G1202R solvent front mutation might hinder the drug binding. In this
      study, a different fact could be clarified by multiple molecular modeling
      methodologies through a structural analogue of ceritinib (compound 10, Cpd-10)
      that is reported to be a potent inhibitor against the G1202R mutation. Herein,
      molecular docking, accelerated molecular dynamics (aMD) simulations in
      conjunction with principal component analysis (PCA), and free energy map
      calculations were used to produce reasonable and representative initial
      conformations for the conventional MD simulations. Compared with Cpd-10, the
      binding specificity of ceritinib between ALK wild-type (ALKWT) and ALK G1202R
      (ALKG1202R) are primarily controlled by the conformational change of the P-loop-
      and A-loop-induced energetic redistributions, and the variation is nonpolar
      interactions, as indicated by conventional MD simulations, PCA, dynamic cross
      correlation map (DCCM) analysis, and free energy calculations. Furthermore, the
      umbrella sampling (US) simulations were carried out to make clear the principle
      of the dissociation processes of ceritinib and Cpd-10 toward ALKWT and ALKG1202R.
      The calculation results suggest that Cpd-10 has similar dissociation processes
      from both ALKWT and ALKG1202R, but ceritinib is more easily dissociated from
      ALKG1202R than from ALKWT, thus less residence time is responsible for the
      ceritinib resistance. Our results suggest that both the binding specificity and
      the drug residence time should be emphasized in rational drug design to overcome
      the G1202R solvent front mutation of ALK resistance.

PMID- 29648833
TI  - Manufacturing Amorphous Solid Dispersions with a Tailored Amount of Crystallized
      API for Biopharmaceutical Testing.
AB  - The preparation of an amorphous solid dispersion (ASD) by dissolving a poorly
      water-soluble active pharmaceutical ingredient (API) in a polymer matrix can
      improve the bioavailability by orders of magnitude. Crystallization of the API in
      the ASD, though, is an inherent threat for bioavailability. Commonly, the impact
      of crystalline API on the drug release of the dosage form is studied with samples
      containing spiked crystallinity. These spiked samples possess implicit
      differences compared to native crystalline samples, regarding size and spatial
      distribution of the crystals as well as their molecular environment. In this
      study, we demonstrate that it is possible to grow defined amounts of crystalline
      API in solid dosage forms, which enables us to study the biopharmaceutical impact
      of actual crystallization. For this purpose, we studied the crystal growth in
      fenofibrate tablets over time under an elevated moisture using transmission Raman
      spectroscopy (TRS). As a nondestructive method to assess API crystallinity in ASD
      formulations, TRS enables the monitoring of crystal growth in individual dosage
      forms. Once the kinetic trace of the crystal growth for a certain environmental
      condition is determined, this method can be used to produce samples with defined
      amounts of crystallized API. To investigate the biopharmaceutical impact of
      crystallized API, non-QC dissolution methods were used, designed to identify
      differences between the various amounts of crystalline materials present. The
      drug release in the samples manufactured in this fashion was compared to that of
      samples with spiked crystallinity. In this study, we present for the first time a
      method for targeted crystallization of amorphous tablets to simulate crystallized
      ASDs. This methodology is a valuable tool to generate model systems for
      biopharmaceutical studies on the impact of crystallinity on the bioavailability.

PMID- 29648832
TI  - Hybrid Density Functional Study of the Local Structures and Energy Levels of
      CaAl2O4:Ce3.
AB  - First-principles calculations were carried out for the electronic structures of
      Ce3+ in calcium aluminate phosphors, CaAl2O4, and their effects on luminescence
      properties. Hybrid density functional approaches were used to overcome the well
      known underestimation of band gaps of conventional density functional approaches
      and to calculate the energy levels of Ce3+ ions more accurately. The obtained 4f
      5d excitation and emission energies show good consistency with measured values. A
      detailed energy diagram of all three sites is obtained, which explains
      qualitatively all of the luminescent phenomena. With the results of energy levels
      calculated by combining the hybrid functional of Heyd, Scuseria, and Ernzerhof
      (HSE06) and the constraint occupancy approach, we are able to construct a
      configurational coordinate diagram to analyze the processes of capture of a hole
      or an electron and luminescence. This approach can be applied for systematic high
      throughput calculations in predicting Ce3+ activated luminescent materials with a
      moderate computing requirement.

PMID- 29648834
TI  - Importance of Post-translational Modifications in the Interaction of Proteins
      with Mineral Surfaces: The Case of Arginine Methylation and Silica surfaces.
AB  - Understanding the mechanisms involved in the interaction of proteins with
      inorganic surfaces is of major interest for both basic research and practical
      applications involving nanotechnology. From the list of cellular proteins with
      the highest affinity for silica nanoparticles, we highlighted the group of
      proteins containing arginine-glycine-glycine (RGG) motifs. Biochemical
      experiments confirmed that RGG motifs interact strongly with the silica surfaces.
      The affinity of these motifs is further increased when the R residue is
      asymmetrically, but not symmetrically, dimethylated. Molecular dynamics
      simulations show that the asymmetrical dimethylation generates an electrostatic
      asymmetry in the guanidinium group of the R residue, orientating and stabilizing
      it on the silica surface. The RGG motifs (methylated or not) systematically
      target the siloxide groups on the silica surface through an ionic interaction,
      immediately strengthened by hydrogen bonds with proximal silanol and siloxane
      groups. Given that, in vivo, RGG motifs are often asymmetrically dimethylated by
      specific cellular methylases, our data add support to the idea that this type of
      methylation is a key mechanism for cells to regulate the interaction of the RGG
      proteins with their cellular partners.

PMID- 29648835
TI  - Agonists of G-Protein-Coupled Odorant Receptors Are Predicted from Chemical
      Features.
AB  - Predicting the activity of chemicals for a given odorant receptor is a
      longstanding challenge. Here the activity of 258 chemicals on the human G-protein
      coupled odorant receptor (OR)51E1, also known as prostate-specific G-protein
      coupled receptor 2 (PSGR2), was virtually screened by machine learning using 4884
      chemical descriptors as input. A systematic control by functional in vitro assays
      revealed that a support vector machine algorithm accurately predicted the
      activity of a screened library. It allowed us to identify two novel agonists in
      vitro for OR51E1. The transferability of the protocol was assessed on OR1A1,
      OR2W1, and MOR256-3 odorant receptors, and, in each case, novel agonists were
      identified with a hit rate of 39-50%. We further show how ligands' efficacy is
      encoded into residues within OR51E1 cavity using a molecular modeling protocol.
      Our approach allows widening the chemical spaces associated with odorant
      receptors. This machine-learning protocol based on chemical features thus
      represents an efficient tool for screening ligands for G-protein-coupled odorant
      receptors that modulate non-olfactory functions or, upon combinatorial
      activation, give rise to our sense of smell.

PMID- 29648836
TI  - Chromophore-Removal-Induced Conformational Change in Photoactive Yellow Protein
      Determined through Spectroscopic and X-ray Solution Scattering Studies.
AB  - Photoactive yellow protein (PYP) induces negative phototaxis in Halorhodospira
      halophila via photoactivation triggered by light-mediated chromophore
      isomerization. Chromophore isomerization proceeds via a volume-conserving
      isomerization mechanism due to the hydrogen-bond network and steric constraints
      inside the protein, and causes significant conformational changes accompanied by
      N-terminal protrusion. However, it is unclear how the structural change of the
      chromophore affects the remote N-terminal domain. To understand photocycle
      related structural changes, we investigated the structural aspect of chromophore
      removal in PYP because it possesses a disrupted hydrogen-bond network similar to
      that in photocycle intermediates. A comparison of the structural aspects with
      those observed in the photocycle would give a clue related to the structural
      change mechanism in the photocycle. Chromophore removal effects were assessed via
      UV-vis spectroscopy, circular dichroism, and X-ray solution scattering. Molecular
      shape reconstruction and an experiment-restrained rigid-body molecular dynamics
      simulation based on the scattering data were performed to determine protein
      shape, size, and conformational changes upon PYP bleaching. Data show that
      chromophore removal disrupted the holo-PYP structure, resulting in a small N
      terminal protrusion, but the extent of conformational changes was markedly less
      than those in the photocycle. This indicates that disruption of the hydrogen-bond
      network alone in bleached PYP does not induce the large conformational change
      observed in the photocycle, which thus must result from the organized structural
      transition around the chromophore triggered by chromophore photoisomerization
      along with disruption of the hydrogen-bond network between the chromophore and
      the PYP core.

PMID- 29648837
TI  - Rheology of Ultraswollen Bicontinuous Lipidic Cubic Phases.
AB  - Rheological studies of liquid crystalline systems based on monopalmitolein and 5
      or 8% of 1,2 distearoylphosphatidylglycerol are reported. Such cubic phases have
      been shown to possess unusually large water channels because of their ability of
      accommodating up to 80 wt % of water, a feature that renders these systems
      suitable for crystallizing membrane proteins with large extracellular domains.
      Their mechanical properties are supposed to be substantially different from those
      of traditional cubic phases. Rheological measurements were carried out on cubic
      phases of both Pn3 m and Ia3 d symmetries. It was verified that these
      ultraswollen cubic phases are less rigid than the normal cubic phases, with the
      Pn3 m being softer that the Ia3 d ones. Furthermore, for the Pn3 m case, the
      longest relaxation time is shown to decrease logarithmically with increasing
      surface area per unit volume, proving the critical role of the density of
      interfaces in establishing the macroscopic viscoelastic properties of the
      bicontinuous cubic phases.

PMID- 29648838
TI  - Binding of Small Molecule Drugs to Porcine Vitreous Humor.
AB  - Pharmacokinetics in the posterior eye segment has therapeutic implications due to
      the importance of retinal diseases in ophthalmology. In principle, drug binding
      to the components of the vitreous, such as proteins, collagen, or
      glycosaminoglycans, could prolong ocular drug retention and modify levels of
      pharmacologically active free drug in the posterior eye segment. Since drug
      binding in the vitreous has been investigated only sparsely, we studied vitreal
      drug binding of 35 clinical small molecule drugs. Isolated homogenized porcine
      vitreous and the drugs were placed in a two-compartment dialysis system that was
      used to separate the bound and unbound drug. Free drug concentrations and binding
      percentages were quantitated using LC-MS/MS. Drug binding levels varied between
      21 and 74% in the fresh vitreous and 0 and 64% in the frozen vitreous. The
      vitreal binding percentages did not correlate with those in plasma. Our data
      based pharmacokinetic simulations suggest that vitreal binding of small molecule
      drugs has only a modest influence on the AUC of free drug or drug half-life in
      the vitreous. Therefore, it is likely that vitreal binding is not a major reason
      for interindividual variability in ocular drug responses or drug-drug
      interactions.

PMID- 29648839
TI  - Novel Immunoliposome Technology for Enhancing the Activity of the Agonistic
      Antibody against the Tumor Necrosis Factor Receptor Superfamily.
AB  - We have developed a technology for efficiently enhancing the anticancer apoptosis
      inducing activity of agonistic antibodies against the tumor necrosis factor
      receptor (TNFR) superfamily by the formation of immunoliposomes. To induce
      apoptosis in cancer cells, agonistic antibodies to the TNFR superfamily normally
      need cross-linking by internal immune effector cells via the Fc region after
      binding to receptors on the cell membrane. To develop apoptosis-inducing
      antibodies that do not require the support of cross-linking by immune cells, we
      prepared immunoliposomes conjugated with TRA-8, an agonistic antibody against
      death receptor 5 (DR5), with various densities of antibody on the liposome
      surface, and evaluated their activities. The TRA-8 immunoliposomes exhibited
      apoptosis-inducing activity against various DR5-positive human carcinoma cells at
      a significantly lower concentration without cross-linking than that of the
      original TRA-8 and its natural ligand (TRAIL). The activity of the
      immunoliposomes was correlated with the density of antibodies on the surface. As
      the antibody component, not only the full-length antibody but also the Fab'
      fragment could be used, and the TRA-8 Fab' immunoliposomes also showed
      exceedingly high activity compared with the parental antibody, namely, TRA-8.
      Moreover, cytotoxicity of the TRA-8 full-length or Fab' immunoliposome against
      normal cells, such as human primary hepatocytes, was lower than that for TRAIL.
      Enhanced activity was also observed for immunoliposomes conjugated with other
      apoptosis-inducing antibodies against other receptors of the TNFR superfamily,
      such as death receptor 4 (DR4) and Fas. Thus, immunoliposomes are promising as a
      new modality that could exhibit significant activity at a low dose, for cost
      effective application of an antibody fragment and with stable efficacy
      independent of the intratumoral environment of patients as a TNF superfamily
      agonistic therapy.

PMID- 29648840
TI  - Lewis-Base-Catalyzed Reductive Aldol Reaction To Access Quaternary Carbons.
AB  - A synthetic method for the efficient construction of beta-hydroxylactones and
      lactams bearing alpha-quaternary carbon centers is described. This transformation
      relies on an electronically differentiated Lewis base catalyst, which is uniquely
      capable of promoting a reductive aldol reaction of alpha,alpha-disubstituted and
      alpha,alpha,beta-trisubstituted enones. This approach provides a valuable
      synthetic alternative for carbon-carbon bond formation in complex molecular
      settings due to its orthogonal reactivity compared to that of traditional aldol
      reactions. Based on this method described herein, lactones, lactams, and
      morpholine amides bearing alpha-quaternary carbon centers are accessible in
      yields up to 85% and 50:1 dr.

PMID- 29648841
TI  - Do risk assessment tools help manage and reduce risk of violence and reoffending?
      A systematic review.
AB  - Although it is widely believed that risk assessment tools can help manage risk of
      violence and offending, it is unclear what evidence exists to support this view.
      As such, we conducted a systematic review and narrative synthesis. To identify
      studies, we searched 13 databases, reviewed reference lists, and contacted
      experts. Through this review, we identified 73 published and unpublished studies
      (N = 31,551 psychiatric patients and offenders, N = 10,002 professionals) that
      examined either professionals' risk management efforts following the use of a
      tool, or rates of violence or offending following the implementation of a tool.
      These studies included a variety of populations (e.g., adults, adolescents),
      tools, and study designs. The primary findings were as follows: (a) despite some
      promising findings, professionals do not consistently adhere to tools or apply
      them to guide their risk management efforts; (b) following the use of a tool,
      match to the risk principle is moderate and match to the needs principle is
      limited, as many needs remained unaddressed; (c) there is insufficient evidence
      to conclude that tools directly reduce violence or reoffending, as findings are
      mixed; and (d) tools appear to have a more beneficial impact on risk management
      when agencies use careful implementation procedures and provide staff with
      training and guidelines related to risk management. In sum, although risk
      assessment tools may be an important starting point, they do not guarantee
      effective treatment or risk management. However, certain strategies may bolster
      their utility. (PsycINFO Database Record

PMID- 29648843
TI  - Sidelining the mean: The relative variability index as a generic mean-corrected
      variability measure for bounded variables.
AB  - Variability indices are a key measure of interest across diverse fields, in and
      outside psychology. A crucial problem for any research relying on variability
      measures however is that variability is severely confounded with the mean,
      especially when measurements are bounded, which is often the case in psychology
      (e.g., participants are asked "rate how happy you feel now between 0 and 100?").
      While a number of solutions to this problem have been proposed, none of these are
      sufficient or generic. As a result, conclusions on the basis of research relying
      on variability measures may be unjustified. Here, we introduce a generic solution
      to this problem by proposing a relative variability index that is not confounded
      with the mean by taking into account the maximum possible variance given an
      observed mean. The proposed index is studied theoretically and we offer an
      analytical solution for the proposed index. Associated software tools (in R and
      MATLAB) have been developed to compute the relative index for measures of
      standard deviation, relative range, relative interquartile distance and relative
      root mean squared successive difference. In five data examples, we show how the
      relative variability index solves the problem of confound with the mean, and
      document how the use of the relative variability measure can lead to different
      conclusions, compared with when conventional variability measures are used. Among
      others, we show that the variability of negative emotions, a core feature of
      patients with borderline disorder, may be an effect solely driven by the mean of
      these negative emotions. (PsycINFO Database Record (c) 2018 APA, all rights
      reserved).

PMID- 29648842
TI  - Ethnoracial differences in brain structure change and cognitive change.
AB  - OBJECTIVE: The purpose of this study was to examine longitudinal associations
      between structural MRI and cognition in a diverse sample. METHOD: Older adults (n
      = 444; Mage = 74.5)-121 African Americans, 212 Whites, and 111 Hispanics
      underwent an average of 5.3 annual study visits. Approximately half were
      cognitively normal at baseline (global Clinical Dementia Rating M = 0.5). Of the
      patients with dementia, most (79%) were diagnosed with Alzheimer's disease (AD).
      MRI measures of gray matter volume (baseline and change), and hippocampal and
      white matter hyperintensity (WMH) volumes (baseline), were used to predict change
      in global cognition. Multilevel latent variable modeling was used to test the
      hypothesis that brain effects on cognitive change differed across ethnoracial
      groups. RESULTS: In a multivariable model, global gray matter change was the
      strongest predictor of cognitive decline in Whites and African Americans and
      specific temporal lobe change added incremental explanatory power in Whites.
      Baseline WMH volume was the strongest predictor of cognitive decline in Hispanics
      and made an incremental contribution in Whites. CONCLUSIONS: We found ethnoracial
      group differences in associations of brain variables with cognitive decline. The
      unique patterns in Whites appeared to suggest a greater influence of AD in this
      group. In contrast, cognitive decline in African Americans and Hispanics was most
      uniquely attributable to global gray matter change and baseline WMH,
      respectively. Brain changes underlying cognitive decline in older adults are
      heterogeneous and depend on fixed and modifiable risk factors that differ based
      on ethnicity and race. (PsycINFO Database Record

PMID- 29648844
TI  - Acceptability of nonabstinent treatment outcome goals among addiction treatment
      providers in Ukraine.
AB  - We examined whether acceptability of nonabstinence treatment outcome goals varied
      as a function of a patient's severity of diagnosis (ICD-10 harmful use vs.
      dependence syndrome; World Health Organization, 1992), finality of outcome goal
      (intermediate vs. final), and type of substance (e.g., tobacco, alcohol,
      cannabis), among addiction treatment providers in Ukraine. We surveyed 44% of
      Ukrainian treatment providers (n = 446/1023; Mage = 40.4, SD = 8.6; Male = 67%;
      MYears Of Experience = 10.2, SD = 7.2). For tobacco use, most respondents (78%
      93%) rated nonabstinence as acceptable, regardless of diagnostic severity or
      finality of outcome goal (i.e., intermediate, final). Most respondents also rated
      nonabstinence as acceptable as an intermediate or final goal for patients with
      harmful use of alcohol (70% to 86%) or cannabis (71% to 93%); however,
      nonabstinence was less commonly indicated by respondents as an intermediate goal
      for patients with a dependence syndrome (alcohol = 52%; cannabis = 68%).
      Regarding other drug use, although most rated nonabstinence acceptable as an
      intermediate goal for patients with harmful use of opioids (68%) or sedatives
      (64%), fewer rated nonabstinence acceptable as a final goal (26% to 33%),
      particularly for patients with a dependence syndrome (10% to 27%). Very few
      providers (5% to 15%) rated nonabstinence acceptable for other substances.
      Patients in Ukraine who wish to moderate cannabis or tobacco use will find that
      their provider is typically accepting of this goal; however, providers are mixed
      regarding whether alcohol and opioid moderation is appropriate, particularly for
      those with dependence. Findings support education and research efforts to better
      understand how provider and patient alignment regarding goals impact patient
      outcomes following substance use treatment in Ukraine. (PsycINFO Database Record

PMID- 29648845
TI  - Online and offline awareness deficits: Anosognosia for spatial neglect.
AB  - PURPOSE/OBJECTIVE: Anosognosia for spatial neglect (ASN) can be offline or
      online. Offline ASN is general unawareness of having experienced spatial
      deficits. Online ASN is an awareness deficit of underestimating spatial
      difficulties that likely to occur in an upcoming task (anticipatory ASN) or have
      just occurred during the task (emergent ASN). We explored the relationships among
      spatial neglect, offline ASN, anticipatory ASN, and emergent ASN. Research
      Method/Design: Forty-four survivors of stroke answered questionnaires assessing
      offline and online self-awareness of spatial problems. The online questionnaire
      was asked immediately before and after each of 4 tests for spatial neglect,
      including shape cancellation, address and sentence copying, telephone dialing,
      and indented paragraph reading. RESULTS: Participants were certain they had
      difficulties in daily spatial tasks (offline awareness), in the task they were
      about to perform (anticipatory awareness) and had just performed (emergent
      awareness). Nonetheless, they consistently overestimated their spatial abilities,
      indicating ASN. Offline and online ASN appeared independent. Online ASN improved
      after task execution. Neglect severity was not positively correlated with offline
      ASN. Greater neglect severity correlated with both greater anticipatory and
      emergent ASN. Regardless of neglect severity, we found task-specific differences
      in emergent ASN but not in anticipatory ASN. CONCLUSIONS/IMPLICATIONS:
      Individuals with spatial neglect acknowledge their spatial difficulty (certainty
      of error occurrence) but may not necessarily recognize the extent of their
      difficulty (accuracy of error estimation). Our findings suggest that offline and
      online ASN are independent. A potential implication from the study is that
      familiar and challenging tasks may facilitate emergence of self-awareness.
      (PsycINFO Database Record

PMID- 29648846
TI  - For whose benefit? Comment on the psychobiography special section (2017).
AB  - This commentary addresses a recent special section on psychobiography that
      appeared in the pages of the July-August 2017 American Psychologist. The claims
      made by the authors of these articles raise a number of serious ethical,
      scientific, and historical concerns about psychobiography. These concerns include
      the potential public harm from the indiscriminate analysis of public figures; the
      inherent problem of publicly analyzing individuals without their participation or
      consent; overly deterministic conclusions of such analyses; difficulties
      analyzing figures from a distance and in retrospect; the impossibility of
      validating psychological theories through singular accounts; the presumption that
      psychological knowledge is ahistorical; the highly selective nature of
      psychobiography; and a focus on largely White, male figures as historically
      significant. These issues highlight the potential risks of this approach for both
      individuals under analysis and the broader public, while also questioning the
      professed benefit of psychobiography to psychological science and its value to
      historical scholarship. (PsycINFO Database Record

PMID- 29648847
TI  - Advancing psychobiography: Reply to Young and Collins (2018).
AB  - In this reply to Young and Collins (2018), the author responds to 3 primary
      concerns raised about integrating psychobiography into mainstream psychology:
      appropriate historical context and historiographic research methods, avoiding
      deterministic conclusions and the role of psychobiography in theory testing, and
      ethical concerns related to lack of informed consent of the identified subject.
      The author appreciates the thoughtful comments of Young and Collins and hopes
      that discussion and debate about psychobiography will continue in the literature.
      (PsycINFO Database Record

PMID- 29648848
TI  - Howard B. Eichenbaum (1947-2017).
AB  - Presents an obituary of Howard B. Eichenbaum (1947-2017). Eichenbaum, a world
      leader in the study of memory and the brain, died in Boston, Massachusetts, on
      July 21, 2017, at age 69, following recent spine surgery. Eichenbaum was a hugely
      creative and integrative scientist whose work combined cognitive and lesion
      analyses with high-density neuronal recordings, providing insights into brain
      computations and representations that help bridge psychological and physiological
      mechanisms of memory. His theories and original and elegant experiments in
      animals have greatly advanced our knowledge of the nature and brain mechanisms of
      memory in animals and humans alike. (PsycINFO Database Record

PMID- 29648849
TI  - Gerald "Jerry" Goldstein (1931-2017).
AB  - Presents an obituary of Gerald "Jerry" Goldstein (1931-2017). Jerry passed away
      at his home in Pittsburgh, Pennsylvania, on April 8, 2017. Goldstein was famous
      for his contributions to the establishment of clinical neuropsychology as a
      science and professional specialty. In addition to his extraordinary service to
      the specialty, he made important contributions to the neuropsychology of
      alcoholism and schizophrenia, as well as to neuropsychological rehabilitation.
      (PsycINFO Database Record

PMID- 29648850
TI  - C. Keith Conners (1933-2017).
AB  - Presents an obituary of C. Keith Conners (1933-2017) who passed away of heart
      failure in Durham, North Carolina, on July 6, 2017. Conners was a pioneer in
      attention-deficit/hyperactivity disorder (ADHD) research and treatment. (PsycINFO
      Database Record

PMID- 29648851
TI  - Eugene T. Gendlin (1926-2017).
AB  - Presents an obituary of Eugene T. Gendlin (1926 -2017) who passed on May 1, 2017,
      at the age of 90 in Spring Hill, New York. Gendlin, an American philosopher and
      psychologist, is perhaps best known for his impact on psychology, psychotherapy,
      and research on the effectiveness of psychotherapy even though he regarded
      himself first as a philosopher. He established the subfield of experiential
      psychotherapy and was the founding editor of the American Psychological
      Association's (APA) Psychotherapy: Theory, Research, and Practice journal.
      (PsycINFO Database Record

PMID- 29648852
TI  - Dorothy G. Singer (1927-2016).
AB  - Presents an obituary of Dorothy G. Singer (1927-2016) who passed away on November
      19, 2016, at Yale New Haven Hospital, at the age of 89. Singer was a professor,
      research scientist, consultant, child therapist, and author. As the author or
      coauthor of more than 25 books and 200 scientific and popular articles, Singer
      brought new insights to child development, particularly in the areas of
      imaginative play and the effects of TV on children. She was a tireless advocate
      for the power of play in children's lives. (PsycINFO Database Record

PMID- 29648853
TI  - Individualized motivational plans in batterer intervention programs: A randomized
      clinical trial.
AB  - OBJECTIVE: Treatment compliance and motivation to change are among the main
      challenges to improving batterer intervention program (BIP) effectiveness. This
      study examined whether adding an individualized motivational plan (IMP) to a
      standard BIP (SBIP) increased intervention effectiveness relative to BIP alone.
      METHOD: One hundred sixty males convicted of intimate partner violence were
      randomly assigned to receive 70 hr of either SBIP or SBIP plus IMP. The IMP is
      based on motivational interviewing, stages of change, and strength-based theory
      principles. We collected the data at baseline, at the end of the 9-month program
      and at 6-month follow-up. Final outcome was recidivism (recidivism data obtained
      from official databases, self-reported recidivism, and therapists' assessment of
      recidivism risk), and proximal outcomes included treatment compliance (dropout
      and intervention dose), and stage of change. We analyzed the results using both
      intent-to-treat (ITT) and per-protocol (PP) approaches. RESULTS: Findings
      indicated that the SBIP plus IMP participants received significantly more
      intervention dose (R2 = .08), finished the intervention in a more advanced stage
      of change (ITT, R2 = .17; PP, R2 = .22), reported less physical violence after
      treatment (ITT, odds ratio = .63; PP, odds ratio = .34), and had a higher
      reduction in recidivism risk (ITT, R2 = .64; PP, R2 = .56) than SBIP
      participants. CONCLUSIONS: These results highlight the relevance of alternative
      approaches, including strategies to increase treatment compliance and motivation
      for change, in BIPs. (PsycINFO Database Record

PMID- 29648854
TI  - Potential mechanisms involved in the effect of cognitive behavioral therapy on
      fatigue severity in Type 1 diabetes.
AB  - OBJECTIVE: To identify mediators of the beneficial effect of cognitive-behavioral
      therapy (CBT) on fatigue severity in chronically fatigued patients with Type 1
      diabetes. METHOD: We performed secondary analyses of a randomized controlled
      trial testing the efficacy of CBT. Primary outcome was fatigue severity assessed
      with the Checklist Individual Strength, subscale fatigue severity. We used
      multiple mediation analysis to determine potential mediators of the treatment
      effect. Proposed mediators were symptom focusing, self-efficacy concerning
      fatigue and pain, perceived activity, sleep disturbances, confidence in diabetes
      self-care, diabetes distress and discrepancy regarding social support. Actigraphy
      was used to assess the level of physical activity. The analysis was repeated with
      depressive symptoms as potential mediator to test whether this caused a change in
      the other fatigue-related mediators. RESULTS: The effect of CBT on fatigue
      severity was partly mediated by a change in symptom focusing (-1.39, 95% CI [
      3.32, -0.19]), fear avoidance (-1.10, 95% CI [-2.49, -0.22]), self-efficacy
      concerning fatigue (-1.95, 95% CI [-4.51, -0.40]), and perceived physical
      activity (-2.44, 95% CI [-4.53, -1.07]). Depressive symptoms were also a mediator
      (-1.22, 95% CI [-2.56, -0.38]), but the aforementioned fatigue-perpetuating
      factors still explained part of the treatment effect. CONCLUSIONS: Changes in
      cognitions about fatigue and activity, and a change in depressive symptoms partly
      mediated the treatment effect of CBT on fatigue severity in Type 1 diabetes. The
      mediators found are similar to those explaining the effects of CBT in other
      chronic diseases. This provides knowledge for the development of more effective
      and efficient interventions for fatigue. (PsycINFO Database Record

PMID- 29648855
TI  - Session-to-session effects of alliance ruptures in outpatient CBT: Within- and
      between-patient associations.
AB  - OBJECTIVE: The concept of alliance ruptures has had a large impact on
      contemporary studies of the alliance. Although this debate mainly focuses on the
      effect of ruptures and repairs on subsequent alliance and outcome levels within
      patients, to date no study has actually examined these within-patient effects.
      The present study fills this lacuna by examining the effect of alliance ruptures
      and in-session repairs on alliance ratings and symptom impairment in the
      subsequent session, accounting for the temporal sequence of ruptures and symptom
      impairment. METHOD: Ruptures and in-session repairs were rated by 1,210 patients
      and 147 therapists using a postsession questionnaire (PSQ-P/-T). Alliance was
      assessed with the Bern postsession reports and symptomatic impairment with the
      Hopkins symptom checklist, short form. RESULTS: Patient- and therapist-reported
      ruptures were significant predictors of subsequent alliance and symptom
      impairment. While sessions in which both patient and therapist perceived a
      rupture were especially detrimental for next session symptom distress, they were
      less damaging to next session alliance levels than sessions in which either only
      the patient or the therapist experienced the rupture. Neither the intensity of
      the rupture nor the perceived level of in-session repair were associated with
      next-session fluctuations in symptom or alliance levels within-patient.
      CONCLUSION: The findings demonstrate the importance of disentangling between- and
      within-patient rupture and in-session repair processes to better understand the
      roles of rupture and repair in treatment. (PsycINFO Database Record

PMID- 29648856
TI  - Treatment expectancy and working alliance in pharmacotherapy as predictors of
      outcomes in complicated grief.
AB  - OBJECTIVE: Nonspecific factors, such as treatment outcome expectancy and working
      alliance, can influence treatment outcome. No studies to date have examined the
      role of expectancy and alliance on pharmacotherapy outcomes in individuals with
      complicated grief (CG). METHOD: This secondary analysis of a larger randomized,
      control trial (RCT) examined the relationship between pharmacotherapy expectancy
      and alliance on treatment outcome in adults with CG who were participating in a
      multisite, double-blind, RCT examining the efficacy of citalopram and complicated
      grief treatment (CGT). Participants (n = 202) were randomized to one of four
      treatment conditions: citalopram (CIT), placebo (PBO), CGT + citalopram (CGT +
      CIT), or CGT + placebo (CGT + PBO). RESULTS: Pharmacotherapy outcome expectancy
      and working alliance were higher among individuals randomized to CGT + CIT and
      CGT + PBO compared with CIT or PBO without CGT. Pharmacotherapy outcome
      expectancy was higher at Week 2 among individuals who ultimately responded to
      treatment compared with those who did not and among those who remained in
      treatment compared with those who dropped out. In contrast, working alliance did
      not correlate with dropout or treatment outcomes in pharmacotherapy. CONCLUSIONS:
      Expectancy for medication was higher among individuals randomized to receive CGT.
      Clinicians should assess symptoms and expectancies in the first weeks of
      treatment because these could be early markers of drop out and treatment
      response. (PsycINFO Database Record

PMID- 29648857
TI  - Associations of patient-rated emotional bond and vocally encoded emotional
      arousal among clinicians and acutely suicidal military personnel.
AB  - OBJECTIVE: To determine if synchrony in emotional arousal and affective
      regulation between patients and clinicians reflect emotional bonding during
      emergency behavioral health appointments. METHOD: Audio recordings of suicide
      risk assessment interviews and crisis intervention planning with 54 suicidal
      active duty soldiers presenting to an emergency department or behavioral health
      clinic were analyzed. Emotional arousal was assessed using mean fundamental
      frequency. Patient-rated emotional bond was assessed with the Working Alliance
      Inventory, Short Form (Hatcher & Gillaspy, 2014). Actor-partner interdependence
      modeling was used to identify moment-to-moment patterns of covariance among
      clinician and patient emotional arousal. RESULTS: Greater synchrony in clinician
      and patient emotional arousal was positively associated with higher emotional
      bond ratings during the crisis intervention but not the risk assessment
      interview. During the risk assessment interview, higher emotional bond was
      associated with a dysregulating effect of the clinician on the patient's
      emotional arousal (i.e., larger fluctuations in the patient's emotional arousal).
      The reverse pattern was seen during the intervention: Higher emotional bond was
      associated with a regulating effect of the clinician on the patient's emotional
      arousal (i.e., smaller fluctuations in the patient's emotional arousal).
      Emotional bond during the intervention was also positively associated with a
      regulating effect of the patient on the clinician's emotional arousal.
      CONCLUSION: Emotional bonding during emergency clinical encounters is associated
      with patient-clinician synchrony in emotional states. During crisis
      interventions, emotional bonding is also associated with mutual down-regulation
      of emotional arousal among patients and clinicians. (PsycINFO Database Record

PMID- 29648858
TI  - The effect of alliance-focused training on a cognitive-behavioral therapy for
      personality disorders.
AB  - OBJECTIVE: To improve success rates in psychotherapy, we developed and evaluated
      an alliance-focused training (AFT) protocol with regard to patient-therapist
      interpersonal behavior in a 30-session protocol of cognitive-behavioral therapy
      (CBT) for outpatients comorbid with Axis I and II conditions. METHOD:
      Participants included 40 patients treated by 40 therapists in a multiple baseline
      design in which novice therapists trained to fidelity standards in CBT were
      introduced to AFT at different time intervals (after either 8 or 16 sessions)
      during a 30-session CBT protocol. Interpersonal behaviors were assessed with a
      simplified version of the Structural Analysis of Social Behavior (SASB) on
      videotaped sessions sampled from the early (between Sessions 6 through 8), mid
      (Sessions 14 through 16), and late (Sessions 22 through 24) phases of therapy.
      RESULTS: As predicted, several significant interactions were observed between
      within-subject interpersonal change and between-groups differences in exposure to
      AFT. Specifically, there were decreases in patient dependence and in therapist
      control (including criticism), plus increases in patient expressiveness and in
      therapist affirmation and expressiveness, all of which could be attributed to
      AFT. The predictive relationship of several of these variables to session-level
      and overall treatment outcome was also demonstrated. CONCLUSIONS: This study
      demonstrates that novice CBT therapists can be trained to improve their
      interpersonal process with patients who present with comorbid diagnoses,
      including a personality disorder. (PsycINFO Database Record

PMID- 29648859
TI  - When therapist estimations of the process of treatment can predict patients
      rating on outcome: The case of the working alliance.
AB  - OBJECTIVE: It has been demonstrated that patient perspective on alliance can
      predict subsequent treatment outcome as reported by the therapist but not the
      other way around. This study aimed to investigate the circumstances in which
      therapists can provide estimations of alliance capable of predicting patient
      perceptions of subsequent session outcome. The study focused on 2 potential
      indicators: time in treatment and treatment efficacy. METHOD: Data of 107
      treatment completers assigned to either cognitive-behavioral therapy or alliance
      focused therapy were analyzed. Data included session-to-session assessments of
      alliance and the session outcome measure across the 30 weeks of treatment as well
      as pretreatment to posttreatment assessments of treatment efficacy using the
      Symptom Checklist-90-Revised. An actor-partner interdependence model of
      longitudinal hierarchically nested data, disentangled for within- and between
      patients effects, was used. The interactive effects of time and treatment
      efficacy and their combined effect were examined. RESULTS: At the sample level,
      as expected, the therapist perspective of alliance did not significantly predict
      patient perception of subsequent session outcome, but significant interaction
      effects were detected. Therapists' perspective on the alliance was a stronger
      predictor of patients' perception of subsequent session outcome when therapy was
      more rather than less effective. This effect was evident mainly early in
      treatment, during which greater variability across dyads was found. CONCLUSIONS:
      Findings suggest that although therapists' ratings of the alliance are not
      consistently predictive of patients' rating of subsequent session outcome, they
      are better predictors in more than in less effective treatments. (PsycINFO
      Database Record

PMID- 29648860
TI  - Motivation and readiness for tobacco cessation among nicotine dependent
      postmenopausal females: A pilot study.
AB  - Despite considerable health risks due to lower levels of estrogen production and
      the compounding antiestrogenic effects of nicotine, postmenopausal females
      continue to smoke. These females face significant barriers to cessation,
      including negative affect, weight concerns, and menopausal symptom severity. The
      current pilot study explored the effect of negative affect, weight concerns, and
      menopausal symptom severity on motivation and readiness to quit smoking. Eighteen
      postmenopausal smokers were randomized to receive brief motivational interviewing
      (B-MI; n = 8) or control treatment (i.e., a 1-hour video, n = 10). Participants
      completed measures of negative affect, weight concerns, and menopausal symptoms,
      as well as measures of motivation and readiness to quit. Motivation and readiness
      to quit were reassessed one week following treatment. At baseline, weight
      concerns, specifically surrounding smoking to prevent overeating, were identified
      as related to increased motivation to quit smoking. Menopausal symptom severity,
      specifically somatic symptoms, assessed at baseline, was associated with
      increased readiness for cessation. B-MI did not increase motivation or readiness
      to quit; however, results indicate that cigarettes per day decreased from
      baseline to follow-up by approximately 20-30%. These results provide valuable
      insight into enhancing engagement in a cessation treatment among this population.
      (PsycINFO Database Record

PMID- 29648861
TI  - An assessment of concurrent cannabidiol and Delta9-tetrahydrocannabinol
      administration in place aversion and taste avoidance conditioning.
AB  - Rising interest in medical marijuana has prompted research into its
      phytocannabinoid constituents, particularly Delta9-tetrahydrocannabinol (THC) and
      cannabidiol (CBD). Coadministration of CBD with THC has been shown to modulate a
      number of THC's effects, including its negative stimulus properties (e.g.,
      anxiety, paranoia, psychosis) in a clinical setting. The present series of
      experiments extended these analyses by examining the ability of CBD to impact the
      aversive effects of THC as assessed in a combined taste and place conditioning
      procedure. In Experiment 1, male and female Wistar rats were given access to a
      novel saccharin solution, injected with a vehicle solution CBD (0.075, 0.75
      mg/kg), THC (0.75 mg/kg) or several combinations of CBD and THC (1:10 or 1:1 dose
      ratio), and then placed in a distinct chamber of a place conditioning apparatus.
      When THC was administered alone, it induced significant place aversions and taste
      avoidance. At both dose ratios, CBD failed to modulate either effect. There were
      no sex differences in either assay or at any ratio. A follow-up experiment
      (Experiment 2) employed identical dose ratios, but a higher dose of THC (7.5
      mg/kg) and corresponding CBD doses (0.75, 7.5 mg/kg). Similar to the initial
      assessment, CBD had no effect on THC-induced place or taste conditioning at
      either dose ratio. These results may reflect the specific phytocannabinoid dose
      ratios examined or species differences in cannabinoid action. The current
      findings further suggest that altering CBD content in medicinal cannabis will
      likely have minimal effects in terms of tolerability. (PsycINFO Database Record

PMID- 29648862
TI  - Two sources of information in reconstructing event sequence.
AB  - Reconstructing memory for sequences is a complex process, likely involving
      multiple sources of information. In 3 experiments, we examined the source(s) of
      information that might underlie the ability to accurately place an event within a
      temporal context. The task was to estimate, after studying each list, the
      temporal position of a single test word within that list. In the first 2
      experiments, we demonstrated that memory for temporal location was better
      following semantic encoding than silent reading of the list, which in turn was
      better than orthographic encoding of the list. Although other measures of
      sequence retention have revealed impaired memory for order with greater item
      level encoding, these experiments demonstrated that item-level encoding improved
      memory for temporal-location. A 3rd experiment extended these findings by
      measuring interitem associations in addition to item memory, demonstrating that
      memory for temporal location within a list was more closely related to item
      information than to interitem relational information. It is now clear that
      reconstructing an event sequence can involve at least 2 distinct sources of
      information-both item and relational encoding can play important roles, depending
      on the nature of the test for order. (PsycINFO Database Record

PMID- 29648863
TI  - Is the phonological similarity effect in working memory due to proactive
      interference?
AB  - Immediate serial recall of verbal material is highly sensitive to impairment
      attributable to phonological similarity. Although this has traditionally been
      interpreted as a within-sequence similarity effect, Engle (2007) proposed an
      interpretation based on interference from prior sequences, a phenomenon analogous
      to that found in the Peterson short-term memory (STM) task. We use the method of
      serial reconstruction to test this in an experiment contrasting the standard
      paradigm in which successive sequences are drawn from the same set of
      phonologically similar or dissimilar words and one in which the vowel sound on
      which similarity is based is switched from trial to trial, a manipulation
      analogous to that producing release from PI in the Peterson task. A substantial
      similarity effect occurs under both conditions although there is a small
      advantage from switching across similar sequences. There is, however, no evidence
      for the suggestion that the similarity effect will be absent from the very first
      sequence tested. Our results support the within-sequence similarity rather than a
      between-list PI interpretation. Reasons for the contrast with the classic
      Peterson short-term forgetting task are briefly discussed. (PsycINFO Database
      Record

PMID- 29648864
TI  - Mechanisms underlying effects of approach-avoidance training on stimulus
      evaluation.
AB  - Over the past decade an increasing number of studies across a range of domains
      have shown that the repeated performance of approach and avoidance (AA) actions
      in response to a stimulus leads to changes in the evaluation of that stimulus.
      The dominant (motivational-systems) account in this area claims that these
      effects are caused by a rewiring of mental associations between stimulus
      representations and AA systems that evolved to regulate distances to positive and
      negative stimuli. In contrast, two recently forwarded alternative accounts
      postulate that AA effects are caused by inferences about the valence of actions
      and stimuli (inferential account) or a transfer of valenced action codes to
      stimulus representations (common-coding account). Across four experiments we set
      out to test these three competing accounts against each other. Experiments 1-3
      illustrate that changes in stimulus evaluations can occur when people perform
      valenced actions that bear no relation to a distance regulation, such as moving a
      manikin upward or downward. The observed evaluative effects were dependent on the
      evaluative implication of the instructed movement goal rather than whether the
      action implied a movement toward or away from the stimuli. These results could
      not be explained with a rewiring of associations to motivational systems.
      Experiment 4 showed that changes in stimulus evaluations occurred after
      participants passively observed approach-avoidance movements, supporting an
      explanation in terms of cognitive inferences. (PsycINFO Database Record

PMID- 29648865
TI  - Production of familiar phrases: Frequency effects in native speakers and second
      language learners.
AB  - Current evidence suggests that native speakers and, to a lesser degree, second
      language learners are sensitive to the frequency with which phrases occur in
      language. Much of this evidence, however, comes from language comprehension.
      While a number of production studies have looked at phrase frequency effects in a
      first language, little evidence exists with respect to the production of phrases
      in a second language. The present study addressed this gap by examining the
      production of English binomial expressions by first and late second language
      speakers. In a phrase elicitation task, participants produced binomial
      expressions (bride and groom) and their reversed forms (groom and bride), which
      are identical in form and meaning but differ in frequency. Mixed-effects modeling
      revealed that native speakers' articulatory durations were modulated by phrase
      frequency, but not the type of stimulus (binomial vs. reversed). Nonnative
      speakers' articulatory durations were not affected either by phrase frequency or
      stimulus type. Our findings provide further evidence for the effect of multiword
      information on language production in native speakers, and raise important
      questions about the effects of phrase frequency on language production in second
      language learners. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 29648866
TI  - A spacing account of negative recency in final free recall.
AB  - The well-known recency effect in immediate free recall reverses when subjects
      attempt to recall items studied and tested on a series of prior lists, as in the
      final-free-recall procedure (Craik, 1970). In this case, the last few items on
      each list are actually remembered less well than are the midlist items. Because
      dual-store theories of recall naturally predict negative recency, this phenomenon
      has long been cited as evidence favoring these models. In a final-free-recall
      study, we replicate the negative-recency effect for the within-list serial
      position curve and the positive-recency effect for the between-list serial
      position curve. Whereas we find prominent negative recency for items recalled
      early in the initial recall period, this effect is markedly reduced for items
      recalled later in the recall period. When considering initial recall as a second
      presentation of studied items, we find that the probability of final free recall
      increases as the number of items between initial presentation and initial recall
      increases. These results suggest that negative recency may reflect the beneficial
      effects of spaced practice, in which end-of-list items recalled early constitute
      massed repetitions and end-of-list items recalled late are spaced repetitions. To
      help distinguish between the spacing account and the prevailing dual-store,
      rehearsal-based account, we examined negative recency in continual-distractor
      free recall. Contrary to the dual-store account, but in accord with the spacing
      account, we find robust negative recency in continual-distractor free recall,
      which is greater for those items recalled early in output. (PsycINFO Database
      Record

PMID- 29648867
TI  - Learning of pitch and time structures in an artificial grammar setting.
AB  - Despite the empirical evidence for the power of the cognitive capacity of
      implicit learning of structures and regularities in several modalities and
      materials, it remains controversial whether implicit learning extends to the
      learning of temporal structures and regularities. We investigated whether (a) an
      artificial grammar can be learned equally well when expressed in duration
      sequences as when expressed in pitch sequences, (b) learning of the artificial
      grammar in either duration or pitch (as the primary dimension) sequences can be
      influenced by the properties of the secondary dimension (invariant vs.
      randomized), and (c) learning can be boosted when the artificial grammar is
      expressed in both pitch and duration. After an exposure phase with grammatical
      sequences, learning in a subsequent test phase was assessed in a grammaticality
      judgment task. Participants in both the pitch and duration conditions showed
      incidental (not fully implicit) learning of the artificial grammar when the
      secondary dimension was invariant, but randomizing the pitch sequence prevented
      learning of the artificial grammar in duration sequences. Expressing the
      artificial grammar in both pitch and duration resulted in disproportionately
      better performance, suggesting an interaction between the learning of pitch and
      temporal structure. The findings are relevant to research investigating the
      learning of temporal structures and the learning of structures presented
      simultaneously in 2 dimensions (e.g., space and time, space and objects). By
      investigating learning, the findings provide further insight into the potential
      specificity of pitch and time processing, and their integrated versus independent
      processing, as previously debated in music cognition research. (PsycINFO Database
      Record

PMID- 29648868
TI  - Does visual salience of action affect gesture production?
AB  - Past research suggests that speakers gesture more when motor simulations are more
      strongly activated. We investigate whether simulations of a perceptual nature
      also influence gesture production. Participants viewed animations of a spider
      moving with a manner of motion that was either highly salient (n = 29) or less
      salient (n = 31) and then described each motion event. Speakers in the high
      salience condition produced significantly more gestures that depicted manner
      information. However, they did not produce significantly more gestures overall,
      more gestures that depicted the spider's path and direction of motion, or more
      manner descriptions in speech. Moreover, the effect of visual salience on manner
      gestures persisted after controlling for expression of manner in speech. These
      findings suggest that speakers selectively produce gestures expressing features
      of perceptual representations that are highly salient. (PsycINFO Database Record

PMID- 29648869
TI  - The role of semantic representations in verbal working memory.
AB  - Two main mechanisms, articulatory rehearsal and attentional refreshing, are
      argued to be involved in the maintenance of verbal information in working memory
      (WM). Whereas converging research has suggested that rehearsal promotes the
      phonological representations of memoranda in working memory, little is known
      about the representations that refreshing may promote. Not only would examining
      this question address this gap in the literature, but the investigation has
      profound implications for different theoretical proposals of how refreshing
      functions and on the relationships between WM and long-term memory (LTM).
      Accordingly, we tested predictions from 5 models regarding how refreshing may
      moderate the semantic representation of memoranda in verbal WM. This series of 4
      experiments presented a cue word that was either semantically or phonologically
      related to a target during the recall phase of a complex span task. Experiment 1
      established the benefit of semantic over phonological retrieval cues, and
      Experiment 2 established that this semantic benefit was specific to a refreshing
      rather than a rehearsal-based maintenance strategy. Finally, we showed that this
      semantic benefit did not vary with the cognitive load of the concurrent task
      (Experiments 3 and 4) or the intention to learn the memoranda (Experiment 4).
      These results indicate that cue-based retrieval from episodic LTM may strongly
      contribute to semantic processing effects in WM recall, but this influence of
      episodic LTM is independent of the function of refreshing to reactivate memory
      traces. Accordingly, these results have strong implications for the functioning
      of refreshing and the links between WM and LTM. (PsycINFO Database Record

PMID- 29648870
TI  - The role of preview validity in predictability and frequency effects on eye
      movements in reading.
AB  - A word's predictability, as measured by its cloze probability, has a robust
      influence on the time a reader's eyes spend on the word, with more predictable
      words receiving shorter fixations. However, several previous studies using the
      boundary paradigm have found no apparent effect of predictability on early
      reading time measures when the reader does not have valid parafoveal preview of
      the target word. The present study directly assesses this pattern in two
      experiments, demonstrating evidence for a null effect of predictability on first
      fixation and gaze duration with invalid preview, supported by Bayes factor
      analyses. While the effect of context independent word frequency is shown to
      survive with invalid preview, consistent with previous studies, the effect of
      predictability is eliminated with both unrelated word previews and random letter
      string previews. These results suggest that a word's predictability influences
      early stages of orthographic processing, and does so only when perceptual
      evidence is equivocal, as is the case when the word is initially viewed in
      parafoveal vision. Word frequency may influence not only early orthographic
      processing, but also later processing stages. (PsycINFO Database Record

PMID- 29648871
TI  - Semantic and functional relationships among objects increase the capacity of
      visual working memory.
AB  - Visual working memory (VWM) has a limited capacity of approximately 3-4 visual
      objects. Current theories of VWM propose that a limited pool of resources can be
      flexibly allocated to objects, allowing them to be represented at varying levels
      of precision. Factors that influence the allocation of these resources, such as
      the complexity and perceptual grouping of objects, can thus affect the capacity
      of VWM. We sought to identify whether semantic and functional relationships
      between objects could influence the grouping of objects, thereby increasing the
      functional capacity of VWM. Observers viewed arrays of 8 to-be-remembered objects
      arranged into 4 pairs. We manipulated both the semantic association and
      functional interaction between the objects, then probed participants' memory for
      the arrays. When objects were semantically related, participants' memory for the
      arrays improved. Participants' memory further improved when semantically related
      objects were positioned to interact with each other. However, when we increased
      the spacing between the objects in each pair, the benefits of functional but not
      semantic relatedness were eliminated. These findings suggest that action-relevant
      properties of objects can increase the functional capacity of VWM, but only when
      objects are positioned to directly interact with each other. (PsycINFO Database
      Record

PMID- 29648872
TI  - The misinterpretation of noncanonical sentences revisited.
AB  - Most current models of sentence comprehension assume that the human parsing
      mechanism (HPM) algorithmically computes detailed syntactic representations as
      basis for extracting sentence meaning. These models share the assumption that the
      representations computed by the HPM accurately reflect the linguistic input. This
      assumption has been challenged by Ferreira (2003), who showed that comprehenders
      sometimes misinterpret unambiguous sentences in which subject and object appear
      in noncanonical order, such as passives or object-clefts. According to Ferreira,
      these misinterpretations show that parallel to an algorithmic analysis, the HPM
      performs a heuristic analysis sometimes resulting in interpretations not licensed
      by the grammar. Our study investigated whether misinterpretation effects indeed
      reflect an erroneous mapping of form to meaning due to heuristic processing
      strategies. Using an experimental design closely following Ferreira (2003),
      Experiment 1 demonstrates that errors with noncanonical sentences show up in
      German as well, despite the fact that German provides morphological case, which a
      heuristic strategy should use. Experiment 2 required participants to judge the
      plausibility of the same sentences. With this task, no evidence for
      misinterpretation of noncanonical sentences was found. Taken together, our
      results suggest that misinterpretation errors do not reflect errors in the
      mapping of form to meaning, but task-specific difficulties that arise when
      participants retrieve information from the memory representation of a sentence.
      Consequently, misinterpretation errors do not provide evidence for the claim that
      the HPM pursues a heuristic analysis in addition to an algorithmic analysis. Our
      results instead lend support to models of the HPM that assume algorithmic
      processing only. (PsycINFO Database Record

PMID- 29648873
TI  - The benefits of retrieval practice depend on item difficulty and intelligence.
AB  - The authors examined whether individual differences in fluid intelligence (gF)
      modulate the testing effect. Participants studied Swahili-English word pairs and
      repeatedly studied half the pairs or attempted retrieval, with feedback, for the
      remaining half. Word pairs were easy or difficult to learn. Overall, participants
      showed a benefit of testing over restudy. However, almost 1/3 of the sample had a
      negative testing effect and benefitted more from restudy than testing, as well as
      performing better overall. These individuals self-reported less use of shallower
      encoding strategies than positive testing effect participants but did not differ
      in other dimensions. For individuals with a positive testing effect, difficulty
      had differential effects on participants who scored high or low on a measure of
      gF, with high gF participants showing larger testing effects for difficult over
      easy items, whereas low gF participants showed the opposite. Working memory
      performance was not related to the magnitude of the testing effect; however,
      vocabulary knowledge revealed a similar pattern as gF, with higher vocabulary
      associated with a testing effect for difficult but not easy items. This suggests
      that the benefit of retrieval practice varies with item difficulty and
      participant abilities. Thus, recommendations to engage in retrieval practice
      should take into consideration the interactive effects of to-be-learned materials
      and individual differences in the learners. (PsycINFO Database Record

PMID- 29648874
TI  - Piloting of COPES: An Empirically Informed Psychosocial Intervention on an
      Adolescent Psychiatric Inpatient Unit.
AB  - OBJECTIVES: This study evaluated the feasibility and initial efficacy of an
      empirically informed psychosocial intervention on an adolescent psychiatric
      inpatient unit. METHODS: Data were obtained for 463 adolescents 12-16 years of
      age on a psychiatric inpatient unit. Information collected included demographics,
      psychiatric diagnoses, length of inpatient stay, completion of four treatment
      modules, rehospitalizations, and emergency room visits during 12 months after
      discharge from index admission. RESULTS: Around 98.70% of patients completed at
      least one out of the four treatment modules and 93.95% of patients completed two
      modules. There were no significant barriers to completing treatment modules on
      the basis of participant characteristics (demographics, psychiatric diagnosis,
      number of diagnoses, or length of stay). Completion of the four treatment
      modules, particularly modules on developing a safety plan and enhancing life,
      predicted lower risk for rehospitalization and emergency room contact in the 12
      months postdischarge. CONCLUSION: Findings suggest that the intervention is
      feasible to implement regardless of common barriers in an inpatient psychiatric
      setting, such as complex psychopathology and brief duration of hospitalization.
      Completion of treatment modules significantly reduces risk for subsequent
      emergency intensive service utilization, suggesting this intervention may be an
      effective method for reducing acute clinical events.

PMID- 29648876
TI  - Use of Patient-Specific 3D-Printed Titanium Implants for Complex Foot and Ankle
      Limb Salvage, Deformity Correction, and Arthrodesis Procedures.
AB  - BACKGROUND: The advancement of 3D printing technology has allowed for the use of
      custom-designed implants for difficult-to-treat foot and ankle pathologies. This
      study reports on the radiographic and functional outcomes of a case series of
      patients treated with patient-specific 3D-printed titanium implants. METHODS:
      Fifteen consecutive patients treated with custom-designed 3D-printed implant
      cages for severe bone loss, deformity correction, and/or arthrodesis procedures
      were included in this study. A minimum of 1 year of clinical and radiographic
      follow-up was required. No patients were lost to follow-up. Patients completed a
      visual analog scale for pain, the Foot and Ankle Ability Measure Activities of
      Daily Living score, and the American Orthopaedic Foot & Ankle Society Score
      outcomes questionnaires preoperatively and at most recent follow-up. All patients
      had postoperative radiographs and computed tomography (CT) scans to assess bony
      incorporation. The mean age was 53.3 years (range, 22-74 years) with a mean
      follow-up of 22 months (range, 12-48 months) for these 15 patients. RESULTS:
      Radiographic fusion verified by CT scan occurred in 13 of 15 patients. There was
      significant improvement in pain and all functional outcome score measures. All
      patients who went on to fusion were satisfied with their surgery. There were 2
      failures, consisting of 1 infection and 1 nonunion, with an overall clinical
      success rate of 87%. CONCLUSION: These patients demonstrated the successful use
      of patient-specific 3D-printed titanium implants to treat complex large bony
      defects, deformities, and arthrodesis procedures. These implants offer surgeons a
      novel and promising approach to treat both lower extremity pain and deformity
      that is not always available with current techniques. LEVEL OF EVIDENCE: Level
      IV, retrospective case series.

PMID- 29648875
TI  - Regulated Proteolysis in Bacteria.
AB  - Regulated proteolysis is a vital process that affects all living things. Bacteria
      use energy-dependent AAA+ proteases to power degradation of misfolded and native
      regulatory proteins. Given that proteolysis is an irreversible event, specificity
      and selectivity in degrading substrates are key. Specificity is often augmented
      through the use of adaptors that modify the inherent specificity of the
      proteolytic machinery. Regulated protein degradation is intricately linked to
      quality control, cell-cycle progression, and physiological transitions. In this
      review, we highlight recent work that has shed light on our understanding of
      regulated proteolysis in bacteria. We discuss the role AAA+ proteases play during
      balanced growth as well as how these proteases are deployed during changes in
      growth. We present examples of how protease selectivity can be controlled in
      increasingly complex ways. Finally, we describe how coupling a core recognition
      determinant to one or more modifying agents is a general theme for regulated
      protein degradation.

PMID- 29648877
TI  - Role of mitophagy regulation by ROS in hepatic stellate cells during acute liver
      failure.
AB  - Liver sinusoids serve as the first line of defense against extrahepatic stimuli
      from the intestinal tract. Hepatic stellate cells (HSCs) are pericytes residing
      in the perisinusoidal space that integrate cytokine-mediated inflammatory
      responses in the sinusoids and relay these signals to the liver parenchyma.
      Oxidative stress has been shown to promote inflammation during acute liver
      failure (ALF). Whether and how oxidative stress is involved in HSC inflammation
      during ALF remains unclear. Level of systemic oxidative stress is reflected by
      superoxide dismutase (SOD). Thus, ALF patients were recruited to investigate the
      correlation between plasma SOD levels and clinical features. Liver tissues were
      collected from chronic hepatitis patients by biopsy and from ALF patients who had
      undergone liver transplantation. SOD2 expression and HSCs activation were
      investigated by immunohistochemistry. Inflammation, mitophagy, and apoptosis were
      investigated by immunoblot analysis and flow cytometry in HSCs treated with
      lipopolysaccharide (LPS) and reactive oxygen species (ROS) donors. The plasma SOD
      level was significantly increased in patients with ALF compared with those with
      cirrhosis (444.4 +/- 23.58 vs. 170.07 +/- 3.52 U/ml, P < 0.01) and was positively
      correlated with the Model for End-Stage Liver Disease-Na score ( R2 = 0.4720, P <
      0.01). In vivo observations revealed that SOD2 immunostaining was increased in
      ALF patients and mice models, and in vitro experiments demonstrated that LPS/ROS
      promoted inflammation via inhibiting mitophagy. Moreover, the regulation of
      inflammation was apoptosis independent in HSCs. LPS-induced increases in
      oxidative stress promote inflammation through inhibiting mitophagy in HSCs during
      the process of ALF, providing a novel strategy for the treatment of patients with
      ALF. NEW & NOTEWORTHY Here we demonstrate that the serum superoxide dismutase
      (SOD) level is significantly increased in patients with acute liver failure
      (ALF), and, correlated with the Model for End-Stage Liver Disease-Na score, SOD
      level dropped in the remission stage of ALF. We identify that, in liver tissue
      from ALF patients and mice models, manganese-dependent SOD was overexpressed, and
      show lipopolysaccharide/H2O2 inhibits mitophagy via reactive oxygen species in
      hepatic stellate cells (HSCs). We show that inhibited mitophagy promotes
      inflammation in HSCs, whereas mitophagy inducer rescues HSCs from
      lipopolysaccharide-induced inflammation.

PMID- 29648879
TI  - Erratum.

PMID- 29648880
TI  - Evolving Challenges in Pediatric Pulmonary Medicine. New Opportunities to
      Reinvigorate the Field.

PMID- 29648878
TI  - Protective effect of Lactobacillus reuteri DSM 17938 against experimental
      necrotizing enterocolitis is mediated by Toll-like receptor 2.
AB  - Lactobacillus reuteri DSM 17938 (LR 17938) has been shown to reduce the incidence
      and severity of necrotizing enterocolitis (NEC). It is unclear if preventing NEC
      by LR 17938 is mediated by Toll-like receptor 2 (TLR2), which is known to mediate
      proinflammatory responses to bacterial cell wall components. NEC was induced in
      newborn TLR2-/- or wild-type (WT) mice by the combination of gavage-feeding cow
      milk-based formula and exposure to hypoxia and cold stress. Treatment groups were
      administered formula supplemented with LR 17938 or placebo (deMan-Rogosa-Sharpe
      media). We observed that LR 17938 significantly reduced the incidence of NEC and
      reduced the percentage of activated effector CD4+T cells, while increasing Foxp3+
      regulatory T cells in the intestinal mucosa of WT mice with NEC, but not in TLR2
      /- mice. Dendritic cell (DC) activation by LR 17938 was mediated by TLR2. The
      percentage of tolerogenic DC in the intestine of WT mice was increased by LR
      17938 treatment during NEC, a finding not observed in TLR2-/- mice. Furthermore,
      gut levels of proinflammatory cytokines IL-1beta and IFN-gamma were decreased
      after treatment with LR 17938 in WT mice but not in TLR2-/- mice. In conclusion,
      the combined in vivo and in vitro findings suggest that TLR2 receptors are
      involved in DC recognition and DC-priming of T cells to protect against NEC after
      oral administration of LR 17938. Our studies further clarify a major mechanism of
      probiotic LR 17938 action in preventing NEC by showing that neonatal immune
      modulation of LR 17938 is mediated by a mechanism requiring TLR2. NEW &
      NOTEWORTHY Lactobacillus reuteri DSM 17938 (LR 17938) has been shown to protect
      against necrotizing enterocolitis (NEC) in neonates and in neonatal animal
      models. The role of Toll-like receptor 2 (TLR2) as a sensor for gram-positive
      probiotics, activating downstream anti-inflammatory responses is unclear. Our
      current studies examined TLR2 -/- mice subjected to experimental NEC and
      demonstrated that the anti-inflammatory effects of LR 17938 are mediated via a
      mechanism requiring TLR2.

PMID- 29648882
TI  - Endobronchial Mucormycosis Successfully Treated with Flexible Bronchoscopic
      Cryotherapy.

PMID- 29648881
TI  - Chronic Obstructive Pulmonary Disease: Abandoning the "Streetlight Effect".

PMID- 29648885
TI  - Commentary on Testing of Non-Adenocarcinomas.

PMID- 29648884
TI  - Association between Pulmonary Hypertension and Clinical Outcomes in Hospitalized
      Patients with Sickle Cell Disease.

PMID- 29648886
TI  - BRAF Adds an Additional Piece of the Puzzle to Precision Oncology-Based Treatment
      Strategies in Lung Cancer.

PMID- 29648887
TI  - Molecular Testing for Stage IV Non-Small Cell Lung Cancer Patients With
      Targetable Mutations Following Disease Progression.

PMID- 29648888
TI  - Major Differences in Minor Allometries: A Reply to Moczek.
AB  - By comparing alternative measurements of horn length in the beetle Onthophagus
      taurus, we have investigated why scaling patterns differ between laboratories. We
      show that some measurements are confounded by including part of the head in the
      horn size measurement and consistently underestimate the allometry of horns in
      minor males. Our data show how linear measures that avoid confounding horn length
      with head size produce scaling patterns that support a positive allometry rather
      than a reprogramming model of horn growth. We also found horn volume was highly
      positively allometric this estimate of growth therefore further supports a
      positive allometry model.

PMID- 29648889
TI  - Patient-Reported Allergies Do Not Predict Poorer PROMIS Function, Pain, and
      Depression Scores Following Foot and Ankle Surgery.
AB  - BACKGROUND: Identifying preoperative risk factors that may portend poorer
      operative outcomes remains a topic of current interest. In hip and knee
      arthroplasty patients, the presence of patient-reported allergies (PRAs) has been
      associated with worse pain and function after joint replacement. However, these
      results have not been replicated across studies, including in shoulder
      arthroplasty cases. The impact of PRAs on foot and ankle outcomes has yet to be
      studied. The purpose of our study was to evaluate whether PRAs influence patient
      reported outcome in foot and ankle surgery. METHODS: To determine if PRAs are
      linked to poorer operative outcomes, we retrospectively identified 159 patients
      who underwent elective foot and ankle surgery. PRA data were obtained via chart
      review, and patient-reported outcomes were assessed preoperatively and
      postoperatively via multiple domains, including Patient Reported Outcome
      Measurement Information System (PROMIS) physical function, pain interference, and
      depression measures. Consistent with prior methodology, we compared outcome
      measures (preoperative, postoperative, and the change in outcome scores) between
      patients without self-reported allergies to patients with at least 1 PRA.
      RESULTS: There were 159 patients studied; 79 patients had no allergies listed,
      and 80 patients had at least 1 PRA. Of the 80 patients with at least 1 PRA, there
      were a total of 170 possible allergies. There were no differences in
      preoperative, postoperative, or the change in outcome scores for all PROMIS
      measures (physical function, pain interference, and depression; P > .05) between
      patients with at least 1 PRA and those patients without any listed PRAs.
      CONCLUSIONS: We were unable to prove our hypothesis that PRAs were linked to
      poorer patient-reported outcomes following foot and ankle surgery. Closer review
      of the published reports linking PRAs to worse total joint arthroplasty outcomes
      revealed data that, while statistically significant, are likely not clinically
      relevant. Our negative findings, then, may in fact parallel prior studies on hip,
      knee, and shoulder arthroplasty patients. The presence of PRAs does not appear to
      be a risk factor for suboptimal outcomes in foot and ankle surgery. LEVEL OF
      EVIDENCE: Level III, comparative series.

PMID- 29648890
TI  - Phelligridin D-loaded oral nanotube titanium implant enhances osseointegration
      and prevents osteolysis in rat mandible.
AB  - Poor bone quality and osteolysis are the major causes of implant failure in
      dentistry. Here, this study tested the effect of phelligridin D-loaded nanotubes
      titanium (Ti) for bone formation around the dental implants. The purpose of this
      study was to enhance osseointegration of phelligridin D-loaded implant into the
      bone for bone formation and prevention of osteolysis. Cell viability, crystal
      violet staining, Western blot, alizarin red S staining, alkaline phosphatase
      activity, tartrate-resistant acid phosphatase staining, micro-computed
      tromography (MU-CT), hematoxylin and eosin (H&E) and immunohistochemical staining
      were used in vitro and in vivo to test the biocompatibility of phelligridin D.
      Phelligridin D enhanced osteoblast differentiation and mineralization by
      increasing bone morphogenic protein-2/7 (BMP-2/7), Osterix, Runx-2,
      osteoprotegerin (OPG), alkaline phosphatase and inhibited osteoclast
      differentiation by decreasing receptor activator of nuclear factor kappa-B ligand
      (RANKL) in MC-3T3 E1 cells. Further, phelligridin D promoted bone regeneration
      around nanotube Ti implant surface by increasing the levels of BMP-2/7 and OPG in
      a rat model. Phelligridin D also inhibited osteolysis by suppressing the
      expression of RANKL. These findings strongly suggest that phelligridin D is a new
      compound representing a potential therapeutic candidate for implant failure
      caused by osteolysis and poor bone quality of teeth.

PMID- 29648891
TI  - Muscular and Vascular Issues Induced by Prolonged Standing With Different Work
      Rest Cycles With Active or Passive Breaks.
AB  - OBJECTIVE: The aim of this study was to evaluate the long-lasting motor,
      behavioral, physiological, and perceptual effects of prolonged standing work in
      three work-rest cycle conditions including passive or active rest breaks.
      BACKGROUND: Muscle fatigue has been evidenced after prolonged standing work
      through physiological and neuromotor measures. It has been postulated that muscle
      fatigue induced by prolonged work could be attenuated by appropriate scheduling
      of work and rest periods. However, investigations in this domain remain limited.
      METHOD: Thirty participants simulated standing work for 5 hr with work-rest
      cycles of short, medium, or long standing periods including passive or active
      breaks. Lower-leg muscle twitch force (MTF), muscle oxygenation, lower-leg
      volume, postural stability, force control, and discomfort perception were
      quantified on 2 days. RESULTS: Prolonged standing induced significant changes in
      all measures immediately after 5 hr of work, indicating a detrimental effect in
      long-lasting muscle fatigue, performance, discomfort, and vascular aspects.
      Differences in the measures were not significant between work cycles and/or break
      type. CONCLUSION: Similar physiological and motor alterations were induced by
      prolonged standing. The absence of difference in the effects induced by the
      tested work-rest cycles suggests that simply altering the work-rest cycle may not
      be sufficient to counteract the effects of mainly static standing work. Finally,
      standing for 3 hr or more shows clear detrimental effects. APPLICATION: Prolonged
      standing is likely to contribute to musculoskeletal and vascular symptoms. A
      limitation to less than 3 hr of mostly static standing in occupational activities
      could avoid alterations leading to these symptoms.

PMID- 29648892
TI  - Assessment of the Readiness for Interprofessional Learning Scale (RIPLS): An item
      response theory analysis.
AB  - This short report aims to bring evidence from modern psychometric methods to bear
      on a popularly deployed questionnaire in interprofessional education (IPE)
      assessment. Specifically, three interrelated problems raised against the
      Readiness for Interprofessional Learning Scale (RIPLS) are examined in a study
      with 280 medical and nursing student participants. Firstly, findings support
      RIPLS overall reliability, but fail to support subscale reliabilities. Secondly,
      findings indicate a strong, general factor underlying the RIPLS that supports
      unidimensional interpretations. Thirdly, findings support the RIPLS potential
      sensitivity to changes with appropriate lower ranges for our pre-training student
      sample. Recommendations for refinement to the RIPLS include: use of more
      appropriate reliability indices; factor generalizability; and a subset of items.
      More generally, refinement is possible, whereas RIPLS disuse or continued misuse
      with problematic scales is likely to hinder progress in the field of IPE.

PMID- 29648893
TI  - Ethnohistory and the Dead: Cultures of Colonial Epidemiology.
AB  - What were the dead to colonial epidemiologists? Doctors and colonial scientists
      involved in the response to epidemics of plague in Madagascar in the first half
      of the twentieth century speculated about the role of Malagasy mortuary ritual in
      the spread of plague, and sought to bring Malagasy ritual into line with
      Pasteurian hygienic norms. I examine confrontations over death and the management
      of the dead in Madagascar, tracing the textured form of epidemiological knowledge
      that arose from the confrontation between Malagasy cosmology and Pasteurian
      counter epidemic technique.

PMID- 29648894
TI  - Controlling for Response Bias in Self-Ratings of Personality: A Comparison of
      Impression Management Scales and the Overclaiming Technique.
AB  - Self-serving response distortions pose a threat to the validity of personality
      scales. A common approach to deal with this issue is to rely on impression
      management (IM) scales. More recently, the overclaiming technique (OCT) has been
      proposed as an alternative and arguably superior measure of such biases. In this
      study (N = 162), we tested these approaches in the context of self- and other
      ratings using the HEXACO personality inventory. To the extent that the OCT and IM
      scales can be considered valid measures of response distortions, they are
      expected to account for inflated self-ratings in particular for those personality
      dimensions that are prone to socially desirable responding. However, the results
      show that neither the OCT nor IM account for overly favorable self-ratings. The
      validity of IM as a measure of response biases was further scrutinized by a
      substantial correlation with other-rated honesty-humility. As such, this study
      questions the use of both the OCT and IM to assess self-serving response
      distortions.

PMID- 29648895
TI  - Functional Polymorphisms of the Type 1 and Type 2 Iodothyronine Deiodinase Genes
      in Autoimmune Thyroid Diseases.
AB  - Graves' disease (GD) and Hashimoto's disease (HD) are major autoimmune thyroid
      diseases (AITDs), and their pathological conditions vary among patients. Type 1
      iodothyronine deiodinase (D1) and type 2 iodothyronine deiodinase (D2) convert
      from thyroxine (T4) to triiodothyronine (T3). However, few findings have been
      described concerning the association between polymorphisms in D1 and D2 genes and
      AITD. Therefore, we genotyped D1 rs11206244, D2 rs225014, and rs12885300
      polymorphisms in 134 GD patients, including 54 patients with intractable GD and
      44 patients with GD in remission and 132 HD patients, including 57 patients with
      severe HD, 45 patients with mild HD, and 84 healthy controls using PCR-RFLP. In
      the D2 rs225014 polymorphism, the TT genotype, which was correlated with higher
      D2 activity, was less frequent in AITD, especially in HD, than in control
      subjects (P = 0.0032 and 0.0002, respectively). Moreover, they were also less
      frequent in HD than in GD (P = 0.0199). The TT genotype and T allele were less
      frequent in severe HD and mild HD than in control subjects (P = 0.0003, 0.0006,
      0.0432, and 0.0427, respectively). In conclusion, the low frequency of the TT
      genotype D2 rs225014 polymorphism was associated with the development of AITD and
      severity of HD.

PMID- 29648896
TI  - Does the dysregulation of matrix metalloproteinases contribute to recurrent
      implantation failure?
AB  - INTRODUCTION: The progress in in vitro fertilization (IVF) techniques for
      infertility management has led to the investigation of embryo implantation site
      proteins such as Matrix metalloproteinases (MMPs), which may have a key role in
      embryo-endometrium crosstalk and in the molecular mechanisms of the embryo
      implantation. Areas covered: Numerous studies have generated much information
      concerning the relation between the different proteins at the site of
      implantation such as cytokines, growth factors, adhesion molecules and MMPs.
      However, the exact role of the MMPs in embryo implantation and the impact of
      their dysregulation in recurrent implantation failure have yet to be
      characterized. Expert commentary: The proteomic investigation of the MMPs and
      their molecular pathways may enable scientists and clinicians to correct this
      dysregulation (via appropriate means of prevention and treatment), better manage
      embryo transfer during IVF cycles, and thus increase the ongoing pregnancy rate.

PMID- 29648897
TI  - Meta-analysis of the association of IL2RA polymorphisms rs2104286 and rs12722489
      with multiple sclerosis risk.
AB  - BACKGROUND: The interleukin-2 receptor alpha (IL2RA) gene polymorphisms may be
      implicated in the genetic susceptibility to multiple sclerosis (MS). This meta
      analysis aims to evaluate the relationship of the IL2RA polymorphisms rs2104286
      and rs12722489 with MS risk in different populations. METHODS: Eligible
      association studies were identified through search in Pubmed, Medline, Web of
      Science, and Scopus (end of search: August 2017). Summary odds ratios (ORs) with
      95% confidence intervals (CIs) were calculated using random-effects or fixed
      effects models. All statistical analyses were two-sided. RESULTS: Eleven studies
      including 8608 cases and 9061 controls evaluated rs2104286. The results
      demonstrated that the A allele of rs2104286 was associated with increased risk of
      MS in Caucasians (OR = 1.19, 95%CI: 1.13-1.25, p < 0.001) and Asians (OR = 1.25,
      95%CI: 1.01-1.55, p = 0.041), respectively. Concerning rs12722489, six studies
      with 4259 cases and 5420 controls were eligible. We found that the C allele of
      rs12722489 was associated with elevated MS risk in Caucasians (OR = 1.20, 95% CI:
      1.12-1.29, p < 0.001) but not in Asians (OR = 1.10, 95%CI: 0.75-1.63, p = 0.629).
      Statistical evidence from the Egger and Begg tests showed absence of publication
      bias. Sensitivity analysis showed that the results were stable. CONCLUSION: Our
      meta-analysis suggests that the rs2104286 A allele is associated with increased
      MS risk in both Caucasians and Asians, whereas the rs12722489 C allele is
      associated with elevated MS risk in Caucasians but not in Asians.

PMID- 29648898
TI  - Use of Standard Guidelines for Department of Medicine Summary Letters.
AB  - : Phenomenon: Fourth-year medical students obtain Department of Medicine (DOM)
      letters ("Chair" letters) to support their residency applications. Writing and
      interpreting DOM letters are challenging. There is heterogeneity in the letters
      that makes it difficult to both write and read these letters. APPROACH: The
      purpose of this study is to determine the value of new guidelines developed by a
      task force of clerkship directors and program directors in internal medicine and
      assess the implementation of these guidelines. The Clerkship Directors in
      Internal Medicine performed a cross-sectional survey of internal medicine
      clerkship directors at U.S. and Canadian medical schools in 2014. In addition,
      the primary author's institution reviewed 1,347 DOM letters between 2012 and 2014
      to assess the implementation of these guidelines. FINDINGS: The survey response
      rate was 78%. DOM letter writers reported the guidelines were better, easier to
      implement, and more compatible with the purpose of DOM letters than previously.
      Most letter readers reported that letters using the guidelines were more
      credible. Writers of DOM letters in lower academic ranks rated the letters with
      guidelines higher in several domains than those in higher academic ranks. Readers
      of DOM letters in higher academic ranks rated the letters with guidelines higher
      in several domains than those in lower academic ranks. In the DOM letters
      examined, the odds of meeting each guideline increased with each additional year.
      However, for 3 guidelines there was an initial decline in adherence from 2012 to
      2013 before increasing again in 2014-the recommended length, clerkship
      description, and detailed narrative guidelines. Letters solely written by a chair
      were less likely to incorporate the guidelines. Insights: Clerkship directors
      often write the DOM letters and identify with the purpose of the guidelines. As
      writers, lower ranking academic faculty value the guidelines more than higher
      ranking academic faculty. As readers of DOM letters, higher academic ranking
      faculty value letters that incorporate the guidelines more than lower academic
      ranking faculty. DOM letters implemented more guideline criteria since the
      guidelines were released. If implementing the guidelines, chairs should solicit
      the help of their clerkship director or educational representative when writing
      DOM letters. Although many clerkship directors read letters for their residency
      programs, additional program directors' opinions are needed.

PMID- 29648899
TI  - Role of Hoxc genes in the development of the limb integumentary organ (nail,
      claw, or hoof).
AB  - The developing vertebrate limb has long proved as an excellent system for
      studying the mechanisms involved in pattern formation and morphogenesis and more
      recently in transcriptional regulation and morphological evolution. To elucidate
      the stage-specific expression profiles of the components of the developing limb,
      we have generated the temporal transcriptome of the limb progenitors and of the
      overlying ectoderm separately. Our study has uncovered a collinear activation of
      Hoxc genes in the limb ectoderm that we have validated by in situ hybridization.
      However, while members of the HoxA and HoxD clusters show complex and dynamic
      patterns of expression during limb development that correlate with the morphology
      of the different limb segments, no specific function for the HoxC or HoxB
      clusters has been identified ( 1 - 3 ). To investigate the function of Hoxc genes
      in the limb ectoderm, we have reexamined the HoxC cluster null mice. Remarkably,
      and despite exhibiting normal terminal phalanges, these mice didn't form claws
      (anonychia). Morphological and immunohistochemical analysis identified a failure
      in the differentiation of the main components of the nail/claw organ. To unravel
      the transcriptional regulation of Hoxc genes in the limb ectoderm, we used the
      ATACseq technique. Using this approach, we identified two putative regulatory
      regions which activity was tested in mouse transgenic enhancer assays. It is
      currently considered that Hox genes have played a key role in the evolution of
      morphological traits, probably associated with changes in their regulatory
      landscapes ( 4 ). Given that the form and size of the distal limb integumentary
      organ (nail, claw or hoof) correlates with that of the distal phalanx and that
      the development of hooves was a major innovation in the evolution of a cursorial
      lifestyle, we are also exploring the possible implication of Hoxc genes in the
      nail/claw/hoof transition. This abstract is from the Experimental Biology 2018
      Meeting. There is no full text article associated with this abstract published in
      The FASEB Journal.

PMID- 29648900
TI  - No evidence of disease activity in patients receiving fingolimod at private or
      academic centers in clinical practice: a retrospective analysis of the multiple
      sclerosis, clinical, and magnetic resonance imaging outcomes in the USA (MS
      MRIUS) study.
AB  - OBJECTIVE: The impact of multiple sclerosis (MS) center type on outcomes has not
      been investigated. This study aimed to evaluate baseline characteristics and
      clinical and magnetic resonance imaging (MRI) outcomes in patients with MS
      receiving fingolimod over 16 months' follow-up at private or academic centers in
      the USA. METHODS: Clinical and MRI data collected in clinical practice from
      patients initiating fingolimod were stratified by center type and retrospectively
      analyzed. No evidence of disease activity (NEDA-3) was defined as patients with
      no new/enlarged T2/gadolinium-enhancing lesions, no relapses, and no disability
      progression (Expanded Disability Status Scale scores). RESULTS: Data were
      collected for 398 patients from 25 private centers and 192 patients from eight
      academic centers. Patients were older (median age = 43 vs 41 years; p = .0047)
      and had a numerically shorter median disease duration (7.0 vs 8.5 years; p =
      .0985) at private vs academic centers. Annualized relapse rate (ARR) was higher
      in patients at private than academic centers in the pre-index (0.40 vs 0.29; p =
      .0127) and post-index (0.16 vs 0.08; p = .0334) periods. The opposite was true
      for T2 lesion volume in the pre-index (2.86 vs 5.23 mL; p = .0002) and post-index
      (2.86 vs 5.11 mL; p = .0016) periods; other MRI outcomes were similar between
      center types. After initiating fingolimod, ARRs were reduced, disability and most
      MRI outcomes remained stable, and a similar proportion of patients achieved NEDA
      3 at private and academic centers (64.1% vs 56.1%; p = .0659). CONCLUSION:
      Patient characteristics differ between private and academic centers. Over 55% of
      patients achieved NEDA-3 during fingolimod treatment at both center types.

PMID- 29648901
TI  - Training Health Professions preceptors in rural practices: A challenge for
      Interprofessional practice and education.
AB  - The ever-increasing mandate for interprofessional practice and education (IPE)
      faces challenges in rural settings. Oregon Health & Science University (OHSU)
      launched a preceptor development program as part of its commitment to training
      interprofessional student groups in rural settings. The objectives of the program
      were to (1) encourage preceptors to exemplify team behaviors; (2) characterize
      contemporary learners and learning styles of trainees; (3) encourage
      interprofessional precepting skills, and (4) apply practical teaching tools in
      the clinical setting. This was a qualitative observational project performed at
      OHSU rural faculty primary care clinics. Subjects were a convenience sample of
      rural interprofessional preceptors who volunteered to participate. Each
      educational session was based on a prior interview identifying their specific
      training needs. Data analysis was based on results from an evaluation survey and
      comments from providers at these sites. Key factors such as dedicated time for
      preceptor development, good communication between the rural practices and the
      academic health center, and concerns about billing revenue were discovered to be
      critical to the success of the program.

PMID- 29648902
TI  - Diagnostic evaluation in steroid-induced myopathy: case report suggesting
      clinical utility of quantitative muscle ultrasonography.
AB  - PURPOSE: We present a patient with adrenal Cushing's syndrome causing steroid
      myopathy. The purpose of the case report is to illustrate the clinical usefulness
      of quantitative muscle ultrasonography for the assessment of glucocorticoid
      induced changes in muscle mass (MM) and structure. METHODS: Assessments of
      physical performance, muscle strength, MM (i.e., total body skeletal MM,
      appendicular skeletal MM, and thickness of lower limb muscles), and muscle
      structure (i.e., echo intensity of lower limb muscles) were performed in the
      patient both in the active phase of the disease (preoperatively) and 6 months
      after surgical intervention (postoperatively). RESULTS: Muscle strength, physical
      performance, and MM were low both preoperatively and postoperatively. We also
      found preoperatively an increased echo intensity that normalized postoperatively.
      CONCLUSIONS: Clinical implications of these findings are double-fold. First,
      although the muscle structure can recover quickly in steroid myopathy patients,
      the recovery of MM may take months to years. Second, we show that muscle echo
      intensity can be useful to track the progression of steroid myopathy overtime and
      may help to indicate early response to therapeutic interventions. Further
      prospective studies are needed to confirm the value of muscle echo intensity in
      patients with endogenous or exogenous Cushing's syndrome presenting with steroid
      myopathy.

PMID- 29648903
TI  - Cardiotoxicity of anthracycline (ANT) treatment in children with malignant
      tumors.
AB  - OBJECTIVE: To investigate the cardiotoxicity indexes in children with malignant
      tumors after the administration of anthracycline (ANT) chemotherapy. MATERIALS
      AND METHODS: Data from 131 children with malignant tumors who were treated using
      ANT chemotherapy at our hospital from January 2011 to December 2015 were
      collected to analyze the serologic indexes (such as N-terminal pro-brain
      natriuretic peptide [NT-proBNP] and isoenzyme of creatine kinase [CK-MB]) and
      changes in corrected QT interval(QT-c) and left ventricular ejection fraction
      (LVEF) before and after treatment with different ANT cumulative doses. RESULTS:
      General clinical data revealed that 2 of the 131 children developed clinical
      cardiotoxicity. The ANT cumulative dose range was 12-697 mg/m2. All patients were
      divided into three groups according to the ANT cumulative dose: group 1 (<100
      mg/m2), 2 (>=100 and <200 mg/m2), and 3 (>=200 mg/m2). Although NT-proBNP and
      LVEF among the three groups differed significantly after chemotherapy (p = 0.022
      and 0.035, respectively), no significance was noted for CK-MB and QT-c among the
      three groups after chemotherapy (p = 0.190 and p = 0.084, respectively). Multiple
      linear regression analysis revealed that the ANT cumulative dose had the most
      significant impact on NT-proBNP (standardized coefficient 0.423, p = 0). Pearson
      correlation analysis revealed that ANT cumulative dose was positively correlated
      with NT-proBNP post-treatment (correlation coefficient 0.423), but LVEF was
      negatively correlated with NT-proBNP after chemotherapy (correlation coefficient 
      0.542). CONCLUSIONS: NT-proBNP showed significant changes when the ANT dose was
      >200 mg/m2. Post-treatment serum NT-proBNP was linearly correlated with ANT
      cumulative dose, hence strictly controlling the ANT cumulative dose and
      monitoring serum NT-proBNP may have certain clinical significance in predicting
      cardiotoxicity.

PMID- 29648904
TI  - Inflammatory cytokines and depression in children with cancer: A review of the
      literature.
AB  - Compared to the general pediatric population, pediatric cancer patients are at
      increased risk of experiencing depressive symptoms during and after their
      treatment. Clinically, there exist few resources to guide health care
      professionals in the care of children with cancer who report depressive
      symptomatology. Pediatric cancer patients experience unique inflammatory changes
      secondary to their disease and accompanying treatments. It has been reported that
      inflammatory changes in the context of illness are related to cytokine
      dysregulation which in turn may influence the expression of depressive symptoms.
      In this review of current literature, we summarize the existing knowledge,
      relevant models and studies in progress with respect to this concept.

PMID- 29648906
TI  - The Effects of a Community-Based Lifestyle Intervention on Metabolic Syndrome and
      Its Components in Adolescents: Findings of a Decade Follow-Up.
AB  - BACKGROUND: The increasing prevalence of metabolic syndrome (MetS) in childhood
      makes lifestyle interventions imperative during adolescence. This study aimed to
      assess the effects of a community-based lifestyle intervention on MetS and its
      components in adolescents. METHODS: Adolescents, based on their residential area
      were categorized into three groups: complete intervention (residing in the
      intervention area at baseline and during all follow-ups), incomplete intervention
      (residing in either the intervention or control areas and were in transition
      between these two areas), and control group (residing in the control area at
      baseline and throughout all follow-ups). All measurements were repeated every 3
      years for up to 9 years. Lifestyle intervention aimed at achieving healthy
      dietary patterns and increasing physical activity. Generalized estimating
      equation models were used to analyze data. RESULTS: In boys with incomplete
      intervention versus controls, the prevalence of MetS was significantly lower in
      the short term (14.0 vs. 22.9), but not in long term. In boys with complete
      intervention, the prevalence was significantly lower versus controls (9.0 vs.
      23.4) in the long term. In girls, the short-term prevalence of MetS was
      significantly lower in the complete intervention group compared with controls
      (2.5 vs. 9.1) and then remained constantly low in all study groups after that.
      Among MetS components, in boys, triglycerides and fasting plasma glucose in the
      short term and high-density lipoprotein mid term, and in girls HDL in mid and
      long term were both significantly improved. The odds of MetS decreased
      significantly in the complete [odds ratio (OR): 0.516, confidence interval (95%
      CI): 0.273-0.973] and incomplete (OR: 0.591, 95% CI: 0.358-0.976) intervention
      groups only in boys. The short- and long-term interventions resulted improvement
      in some of the MetS components in both genders. CONCLUSIONS: The healthy
      lifestyle intervention reduced the risk of MetS in both genders in short and long
      term, but with different patterns and improved some of the MetS components.

PMID- 29648907
TI  - Impact of coping strategies on quality of life of adolescents and young women
      with endometriosis.
AB  - PURPOSE: Endometriosis is a hormone-dependent, inflammatory, painful condition
      affecting 1 in 10 women during their reproductive years. The symptoms of
      endometriosis-dysmenorrhea, dyspareunia, infertility-negatively impact the
      quality of life (QoL) of the affected women. Few studies have been conducted on
      mental health and QoL impact in a younger endometriosis patient population
      (adolescents and young women). This study quantitative, cross-sectional study was
      designed to address this gap by ascertaining whether coping strategies may impact
      the QoL of this patient population. METHODS: After consent, participants (n = 24)
      completed a sociodemographic questionnaire, Beck Anxiety Inventory (BAI), Beck
      Depression Inventory II (BDI-II), Coping Strategies Inventory (CSI),
      Endometriosis Health Patient-5 (EHP-5) and Visual Analogue Scale (VAS). RESULTS:
      Participants reported the use of both positive and maladaptive strategies to deal
      with the symptomatology, which were associated with QoL levels and mental health
      status. Associations between QoL and maladaptive coping strategies (e.g.
      autocriticism, social withdrawal) were uncovered. Cognitive restructuring was
      identified as an adaptive coping strategy that impacts QoL positively.
      CONCLUSION: These results provide additional evidence showing that endometriosis
      symptoms substantially affect the psychological well-being of young patients and
      identify opportunities for interventions (e.g. cognitive behavioral,
      rational/emotive therapy) to implement coping styles leading to improved QoL.

PMID- 29648908
TI  - Support Needs for Family Caregivers of Clients with Mental Illness in Iran: A
      Qualitative Study.
AB  - This paper explored the support needs of family caregivers of people living with
      a mental illness in Iran. This descriptive study focused on the experiences of 20
      family caregivers as well as the views of 29 professional support workers through
      individual face-to-face interviews. From these interviews three key themes
      emerged in regards to the care needs of family caregivers: (i) social support;
      (ii) emotional support; and (iii) safety and security. These themes highlighted
      the complex role of caring for a family member with a mental illness and the
      emotional, social and economic challenges that these caregivers experienced as a
      result. Iranian caregivers garnered support not only from other family members
      but also from neighbors and religious leaders but lacked the much needed respite
      care found in western countries. This research study highlighted the importance
      of ensuring that the caregivers themselves receive appropriate and adequate
      support to fulfill their caregiving role.

PMID- 29648909
TI  - Diabetes-Related Emergency Medical Service Activations in 23 States, United
      States 2015.
AB  - OBJECTIVE: The use of emergency medical services (EMS) for diabetes-related
      events is believed to be substantial but has not been quantified nationally
      despite the diverse acute complications associated with diabetes. We describe
      diabetes-related EMS activations in 2015 among people of all ages from 23 U.S.
      states. METHODS: We used data from 23 states that reported >=95% of their EMS
      activations to the U.S. National Emergency Medical Services Information System
      (NEMSIS) in 2015. A diabetes-related EMS activation was defined using coded EMS
      provider impressions of "diabetes symptoms" and coded complaints recorded by
      dispatch of "diabetic problem." We described activations by type of location,
      urbanicity, U.S. Census Division, season, and time of day; and patient-events by
      age category, race/ethnicity, disposition, and treatment with glucose. Crude and
      age-adjusted diabetes-related EMS patient-level event rates were calculated for
      adults >=18 years of age with diagnosed diabetes using the Behavioral Risk Factor
      Surveillance System to estimate the population denominator. RESULTS: Of
      10,324,031 relevant EMS records, 241,495 (2.3%) were diabetes-related
      activations, which involved over 235,000 hours of service. Most activations
      occurred in urban or suburban environ- ments (86.4%), in the home setting
      (73.5%), and were slightly more frequent in the summer months. Most patients
      (72.6%) were >=45 years of age and over one-half (55.4%) were transported to the
      emergency department. The overall age-adjusted diabetes-related EMS event rate
      was 33.9 per 1,000 persons with diagnosed diabetes; rates were highest in
      patients 18-44 years of age, males, and non-Hispanic blacks and varied by U.S.
      Census Division. CONCLUSIONS: Diabetes results in a substantial burden on EMS
      resources. Collection of more detailed diabetes complication information in
      NEMSIS may help facilitate EMS resource planning and prevention strategies.

PMID- 29648910
TI  - Usefulness of positron emission tomography-CT for diagnosis of primary bone
      marrow lymphoma in children.
AB  - Primary bone marrow lymphoma (PBML) is hard to diagnose in children, due to the
      difficult identification of malignant cells in bone marrow. The first case, a 5
      year-old boy, showed knee swelling with an intermittent fever. The second case, a
      12-year-old girl, showed fever of unknown origin without lymphadenopathy or
      hepatosplenomegaly. In both cases, the diagnosis was not confirmed despite the
      repeated bone marrow aspirations. Finally, bone marrow aspiration and biopsy at
      the positive site by positron emission tomography (PET)-CT contributed to
      definitive diagnosis of PBML. The PET-CT is useful for the accurate diagnosis of
      PBML in children with non-specific symptoms.

PMID- 29648911
TI  - Body Image Perceptions of Women Veterans with Military Sexual Trauma.
AB  - The researchers were invited to a transitional home for homeless women veterans
      to help veterans with body image issues. Convenience sampling was used to recruit
      12 veterans who perceived they had a physical difference due to military service.
      Data were obtained in focus groups where the veterans were invited to share
      stories. Ricoeur's hermeneutic phenomenology guided the study. The research team
      learned early in the data collection stage that 11 of the 12 participants
      suffered military sexual trauma (MST). Three structures emerged in the data: (a)
      to speak up or not to speak, (b) from military pride to shameful anguish, and (c)
      invisible scars versus visible scars. A phenomenological interpretation of these
      invisible scars uncovered that viewing self in a mirror was depicted as viewing a
      stranger. Being with others, including family, was described as wearing a fake
      face. The phrase I am broken defined intimate relationships which were non
      existent or strained. Shame permeated all body image structures. As the veterans
      listened to each other, they began to see themes in their stories. There was a
      shared sense of identity and a movement toward greater self-understanding and
      resolving. In addition to the recommendations the participants had regarding
      prevention of MST and recovery care of those with MST, implications for research
      and practice are provided.

PMID- 29648912
TI  - Implementing a Trauma-Informed Model of Care in a Community Acute Mental Health
      Team.
AB  - In this paper, we demonstrate the value of implementing a Trauma-Informed Model
      of Care in a Community Acute Mental Health Team by providing brief intensive
      treatment (comprising risk interventions, brief counselling, collaborative
      formulation and pharmacological treatment). The team utilised the Conversational
      Model (CM), a psychotherapeutic approach for complex trauma. Key features of the
      CM are described in this paper using a clinical case study. The addition of the
      Conversational Model approach to practice has enabled better understandings of
      consumers' capacities and ways to then engage, converse, and intervene. The
      implementation of this intervention has led to a greater sense of self-efficacy
      amongst clinicians, who can now articulate a clear counselling model of care.

PMID- 29648913
TI  - Being present with the patient-A critical investigation of bodily sensitivity and
      presence in the field of physiotherapy.
AB  - This article advocates integrating ideas from phenomenological theory regarding
      the body with a psychoanalytical theory of language to enrich our understanding
      of the meaning of bodily presence in the practice of physiotherapy. The authors
      use this theoretical framework to explore bodily presence as a source for
      physiotherapists' professional development. They are using research on children
      as moving and meaning-producing subjects11 The concept of subject is used in
      different ways in phenomenology and psychoanalysis, and also in varying ways in
      each of the two traditions. However, here the concept is used more in line with
      ordinary language, in the sense that it emphasizes the child's active position in
      her/his being in the world. to illustrate the relevance of their perspectives.
      They argue that the perspectives might contribute to a physiotherapeutic practice
      that incorporates bodily presence in the professional language in addition to
      specific methods and techniques. Understanding bodily presence involves the
      physiotherapist recognizing the Other (i.e., the patient/child) in the present
      moment and trusting her/his own capacity to become aware of her/his own bodily
      presence. The authors assert that being aware of one's own bodily presence
      enables therapists to develop an appreciation of their own bodies and the bodies
      of their patients as they are and move in mutual relation to each other. Applying
      the article's theoretical framework, the authors consider the body as the
      starting point for speech,22 The concept of speech is used in a wide sense,
      including voice, tone, and rhythm in line with the article's psychoanalytical
      framework of Kristeva and the late Lacan. Thus, the call for being present for
      the child (as a patient) in the here and now includes participating in the speech
      of the child, even though the child does not use words. and suggest that
      introducing a richer professional language encourages practitioners to become
      more aware of the dialectic between body and language: how the body is the anchor
      for speech and how language influences the experience of the body.

PMID- 29648915
TI  - Response to Modabber and Harissi-Dagher's Letter: "Type 1 Boston Keratoprosthesis
      for Limbal Stem Cell Deficiency in Epidermolysis Bullosa".

PMID- 29648914
TI  - TX99 Is a Neutralizing Monoclonal Antibody Against Mouse TIGIT.
AB  - T cell immunoglobulin and ITIM domains (TIGIT) is an inhibitory immunoreceptor
      expressed on NK cells, effector and memory T cells, and regulatory T cells
      (Tregs). The ligands for TIGIT are CD155 (PVR) and CD112 (PVRL2, nectin-2), which
      are broadly expressed on hematopoietic cells and nonhematopoietic cells. TIGIT
      negatively regulates antitumor responses, but promotes autoimmune reaction.
      Although neutralizing anti-human TIGIT mAbs are under clinical trials for
      cancers, how the blockade of TIGIT interaction with the ligands shows tumor
      immunity still remains unclear. Although analyses of mouse tumor model using a
      neutralizing anti-mouse TIGIT (mTIGIT) mAbs should be useful to address this
      issue, there are limitations to this type of studies due to unavailability of
      neutralizing anti-mTIGIT mAbs. In this study, we generated five clones of anti
      mTIGIT mAbs, designated TX99, TX100, TX103, TX104, and TX105. We show that TX99
      and TX100 showed the strongest binding to TIGIT. We also show that TX99
      interfered with the interaction between TIGIT and CD155 and increased NK cell
      mediated cytotoxicity against CD155-expressing RMA-S cells. Thus, TX99 is a
      unique neutralizing mAb that can be used for studies of mTIGIT functions.

PMID- 29648916
TI  - Comparison of Lipid Accumulation Product Index with Body Mass Index and Waist
      Circumference as a Predictor of Metabolic Syndrome in Indian Population.
AB  - BACKGROUND: Metabolic syndrome (MetS), which confers a high risk for
      cardiovascular diseases, needs early diagnosis and treatment to reduce morbidity
      and mortality. Lipid accumulation product index has been reported to be an
      inexpensive marker of visceral fat and metabolic syndrome. This study aimed to
      evaluate lipid accumulation product index as a marker for metabolic syndrome in
      the Indian population where the prevalence of the condition is steadily
      increasing. METHODS: A hospital-based, case-control study was conducted with 72
      diagnosed cases of metabolic syndrome and 79 control subjects. In all the
      participants, body mass index (BMI) and lipid accumulation product index were
      calculated. The difference between cases and controls in BMI, waist circumference
      (WC), and lipid accumulation product index was assessed by Mann-Whitney U
      test/unpaired t-test. Associations of BMI, WC, and lipid accumulation product
      index with metabolic syndrome were compared by multiple logistic regression
      analysis and receiver operating characteristic analysis. RESULTS: BMI, WC, and
      lipid accumulation product index were significantly higher in metabolic syndrome
      (P < 0.05). Although all were independently associated with metabolic syndrome,
      lipid accumulation product index had the highest prediction accuracy. The
      parameter also had a high area under curve of 0.901 (95% confidence interval 0.85
      0.95) and a high sensitivity (76.4%), specificity (91.1%), positive predictive
      value (88.7%), and negative predictive value (80.9%) for detection of metabolic
      syndrome. CONCLUSION: In the Indian population, lipid accumulation product index
      is a better predictor of metabolic syndrome compared to BMI and WC and should be
      incorporated in laboratory reports as early, accurate, and inexpensive indicator
      of metabolic syndrome.

PMID- 29648917
TI  - Successful treatment of systemic EBV positive T-cell lymphoma of childhood using
      the SMILE regimen.

PMID- 29648918
TI  - Implementation of an Interdisciplinary Communication Workgroup on an Acute
      Psychiatric Unit.
AB  - Communication among Interdisciplinary Healthcare Teams is an essential component
      of providing optimal patient care. Staff members at one U. S. Department of
      Veterans Affairs on an Acute Psychiatric Unit identified fragmented communication
      on the unit and expressed interest in forming an interdisciplinary communication
      workgroup. This quality improvement (QI) project was designed to enhance
      communication among the Interdisciplinary Healthcare Team on the Acute
      Psychiatric Unit. A workgroup was formed and met four times at one-hour
      intervals. A pre/post-test was used to determine the initial effectiveness of the
      intervention. The results of the intervention suggested increased communication
      among the Interdisciplinary Healthcare Team as an upward trend of the mean scores
      was noted.

PMID- 29648919
TI  - Oligomers of styrene are not endocrine disruptors.
AB  - Oligomers of styrene have been identified in polystyrene (PS) polymer samples
      intended for food packaging. Such oligomers contribute to nonintentionally added
      substances (NIAS) that may migrate into food or food simulants and therefore have
      to be assessed for the potential risk to health. No oligomers larger than dimers
      and trimers of styrene have been found to be present in PS. Some in vivo and in
      vitro information indicative of an endocrine activity for some specific oligomers
      suggest concerns for their potential for endocrine disruption in humans. Data on
      endocrine activity available from in vitro and in vivo screening approaches and
      from non-guideline studies in experimental animals were evaluated. The different
      test methods were classified according to the OECD Conceptual Framework for
      Testing and Assessment of Endocrine Disruptors (OECD) and the ranking system of
      Borgert et al. proposed in 2014. The quality and reliability of each study is
      further assessed by professional judgment. The integration of the total
      information supports the conclusion that neither specific oligomers, nor their
      mixtures, potentially migrating into food are endocrine disruptors according to
      the definition of EFSA and WHO/IPCS.

PMID- 29648921
TI  - Optimizing Anticancer Therapy in Metastatic Non-Castrate Prostate Cancer: ASCO
      Clinical Practice Guideline Summary.

PMID- 29648922
TI  - Reducing Wait Time Between Admission and Chemotherapy Initiation.
AB  - PURPOSE: Reducing the length of stay is a high-priority objective for all health
      care institutions. Delays in chemotherapy initiation for planned preadmissions
      lead to patient dissatisfaction and prolonged length of stay. PATIENTS AND
      METHODS: A multidisciplinary team was formed as part of the ASCO Quality Training
      Program. We aimed to reduce the time to initiation of chemotherapy from patient
      arrival at Parkland Hospital from a median of 6.2 hours at baseline to 4 hours
      over a 6-month period (35% reduction). The team identified inconsistency in blood
      work requirements, poor communication, and nonstandard patient arrival times as
      key causes of delay in the process. Plan-Do-Study-Act (PDSA) cycles were
      implemented based on identified improvement opportunities. The outcome measure
      was time from arrival to chemotherapy start. Data were obtained from time stamps
      in the electronic health record. RESULTS: The first PDSA cycle included patient
      reminders to arrive at specific times, improved communication using a smartphone
      secure messaging application, and preadmission notes by oncology fellows
      detailing whether fresh blood work were needed on admission. Baseline data from
      36 patients and postimplementation data from 28 patients were analyzed. Median
      time from admission to chemotherapy initiation preprocess change was 6.2 hours;
      it was 3.2 hours postchange. A sustained shift in the process was apparent on a
      control chart. CONCLUSION: Delays in initiation of chemotherapy can be prevented
      using classic quality improvement methodology and a multidisciplinary team. We
      aim to further refine our PDSA cycles and ensure sustainability of change.

PMID- 29648920
TI  - Functional domain analysis of SOX18 transcription factor using a single-chain
      variable fragment-based approach.
AB  - Antibodies are routinely used to study the activity of transcription factors,
      using various in vitro and in vivo approaches such as electrophoretic mobility
      shift assay, enzyme-linked immunosorbent assay, genome-wide method analysis
      coupled with next generation sequencing, or mass spectrometry. More recently, a
      new application for antibodies has emerged as crystallisation scaffolds for
      difficult to crystallise proteins, such as transcription factors. Only in a few
      rare cases, antibodies have been used to modulate the activity of transcription
      factors, and there is a real gap in our knowledge on how to efficiently design
      antibodies to interfere with transcription. The molecular function of
      transcription factors is underpinned by complex networks of protein-protein
      interaction and in theory, setting aside intra-cellular delivery challenges,
      developing antibody-based approaches to modulate transcription factor activity
      appears a viable option. Here, we demonstrate that antibodies or an antibody
      single-chain variable region fragments are powerful molecular tools to unravel
      complex protein-DNA and protein-protein binding mechanisms. In this study, we
      focus on the molecular mode of action of the transcription factor SOX18, a key
      modulator of endothelial cell fate during development, as well as an attractive
      target in certain pathophysiological conditions such as solid cancer metastasis.
      The engineered antibody we designed inhibits SOX18 transcriptional activity, by
      interfering specifically with an 8-amino-acid motif in the C-terminal region
      directly adjacent to alpha-Helix 3 of SOX18 HMG domain, thereby disrupting
      protein-protein interaction. This new approach establishes a framework to guide
      the study of transcription factors interactomes using antibodies as molecular
      handles.

PMID- 29648923
TI  - Impact on Oncology Practices of Including Drug Costs in Bundled Payments.
AB  - INTRODUCTION: This analysis evaluates the impact of bundling drug costs into a
      hypothetic bundled payment. METHODS: An economic model was created for patient
      vignettes from: advanced-stage III colon cancer and metastatic non-small-cell
      lung cancer. First quarter 2016 Medicare reimbursement rates were used to
      calculate the average fee-for-service (FFS) reimbursement for these vignettes.
      The probabilistic risk faced by practices was captured by the type of patients
      seen in practices and randomly assigned in a Monte Carlo simulation on the basis
      of the given distribution of patient types within each cancer. Simulations were
      replicated 1,000 times. The impact of bundled payments that include drug costs
      for various practice sizes and cancer types was quantified as the probability of
      incurring a loss at four magnitudes: any loss, > 10%, > 20%, or > 30%. A loss was
      defined as receiving revenue from the bundle that was less than what the practice
      would have received under FFS; the probability of loss was calculated on the
      basis of the number of times a practice reported a loss among the 1,000
      simulations. RESULTS: Practices that treat a substantial proportion of patients
      with complex disease compared with the average patient in the bundle would have
      revenue well below that expected from FFS. Practices that treat a
      disproportionate share of patients with less complex disease, as compared with
      the average patient in the bundle, would have revenue well above the revenue
      under FFS. Overall, bundled payments put practices at greater risk than FFS
      because their patient case mix could greatly skew financial performance.
      CONCLUSION: Including drug costs in a bundle is subject to the uncontrollable
      probabilistic risk of patient case mixes.

PMID- 29648925
TI  - Intravenous carbamazepine for the treatment of epilepsy.
AB  - INTRODUCTION: Recently, an intravenous formulation of carbamazepine (CBZ)
      (sulphobutylether-7-beta-cyclodextrine carbamazepine, SBECD CBZ) has been
      developed and approved by the U.S. Food and Drug Administration. It is indicated
      as a short-term replacement therapy for oral CBZ formulations, when oral
      administration is temporarily not feasible and in adults with focal seizures with
      complex symptomatology as well as generalized tonic-clonic seizures and mixed
      seizure patterns. Areas covered: This review focuses on the drug development,
      pharmacokinetics and pharmacodynamics of intravenous CBZ and provides a
      comprehensive overview of the studies assessing its clinical efficacy,
      tolerability and safety in adults with epilepsy. Expert opinion: Intravenous CBZ
      has favorable pharmacokinetics and is well tolerated and safe when used as a
      short-term substitution for oral CBZ. Seizure control was unchanged after
      switching from oral to IV formulations. Overall, this new formulation represents
      a useful option to enhance continuity of care in adults with focal or generalized
      tonic-clonic seizures when oral CBZ administration is temporarily unfeasible.
      Further studies are needed to assess the efficacy and tolerability of IV CBZ used
      at larger doses (above 1600 mg/day), for a period longer than 7 days or for other
      indications not approved by FDA, such as prolonged convulsive seizures and status
      epilepticus.

PMID- 29648926
TI  - HIV/STI interventions targeting women who experience forced sex: A systematic
      review of global literature.
AB  - Women are disproportionately affected by HIV in many regions of the world and
      they represent the fastest growing demographic in the HIV epidemic. In addition,
      sexual violence against women is a global public health issue which increases
      women's vulnerability of HIV/STI acquisition. However, the relationship between
      sexual violence and HIV/STI risk are complex and contribute to the growing
      epidemic of women infected with HIV/STIs. Our purpose for this review is to
      examine existing HIV/STI interventions that target women who experience forced
      sex. Interventions designed to address women's unique needs in HIV/STI prevention
      are critical in reducing women's vulnerability to HIV/STIs.

PMID- 29648924
TI  - Operative Treatment of Isolated Meniscus Injuries in Adolescent Patients: A Meta
      Analysis and Review.
AB  - CONTEXT: With the rise in sports participation and increased athleticism in the
      adolescent population, there is an ever-growing need to better understand
      adolescent meniscus pathology and treatment. OBJECTIVE: To better understand the
      operative management of meniscus tears in the adolescent population. DATA
      SOURCES: A systematic review of PubMed (MEDLINE) and Google Scholar was performed
      for all archived years. STUDY SELECTION: Studies that reported on isolated
      meniscus tears in adolescent patients (age, 10-19 years) were included. STUDY
      DESIGN: Systematic review and meta-analysis. LEVEL OF EVIDENCE: Level 4. DATA
      EXTRACTION: Two authors reviewed and extracted data from studies that fulfilled
      all inclusion criteria. RESULTS: Nine studies on isolated meniscus tears in
      adolescent patients were found, with level of evidence ranging from 3 to 4. These
      studies evaluated a total of 373 patients (248 males, 125 females) and 390 knees.
      Seven studies were published between 1979 and 2000, all of which discuss
      meniscectomy as the primary treatment. Two studies were published after 2000 and
      report on meniscus repair surgery. The mean patient age was 14.4 years. A total
      of 308 meniscectomies and 64 meniscus repairs were performed. Follow-up ranged
      from 1.8 to 30 years (mean, 10.8 years). A 37% retear rate was reported for
      patients undergoing meniscus repair. Different outcome measures were used for
      meniscectomy versus meniscus repair. Three studies evaluating meniscectomy
      reported Tapper-Hoover scores, showing 54 patients with an excellent result, 58
      with good, 57 with fair, and 23 with poor results. CONCLUSION: A shift in the
      management of isolated adolescent meniscal tears is reflected in the literature,
      with a recent increase in operative repair. This is likely secondary to poor
      outcomes after meniscectomy reflected in long-term follow-up studies. The current
      literature highlights the need for improved description of tear patterns,
      standardized reporting of outcome measures, and improved study methodologies to
      help guide orthopaedic surgeons on operative treatment of meniscal tears in
      adolescent patients.

PMID- 29648927
TI  - One Teacher's Experience of Teaching Physical Education and Another School
      Subject: An Inter-Role Conflict?
AB  - PURPOSE: This study was situated within a longitudinal study of 5 teachers
      examining the realities of teaching physical education by determining the impact
      of individual dispositions and contextual factors on the career trajectories of
      postprimary physical education teachers in Ireland (Iannucci & MacPhail, 2017).
      One of these participants, Jane, was examined in this study to gain a greater
      understanding of the realities and tensions experienced by a postprimary teacher
      enacting 2 distinct sets of role expectations when teaching physical education
      and another school subject concurrently. METHOD: Data reported in this article
      were collected through a semistructured interview and living graph. An
      interpretative framework was used for analysis, assessing Jane's perceived
      meanings of the identified critical incidents in relation to role theory.
      RESULTS: Teachers timetabled with physical education and another subject
      concurrently may be expected to navigate and negotiate 2 distinctly different
      roles within the school community causing difficulty in assuming both roles
      simultaneously. Short narratives were used to convey 2 themes: (a) role
      prioritization and (b) role performance. CONCLUSION: The study results suggest
      that the already complex and multifaceted role of a school teacher (Richards,
      Templin, Levesque-Bristol, & Blankenship, 2014) seems to be further complicated
      when teachers are tasked with simultaneously teaching physical education and
      another school subject. With the presence of a role conflict management strategy
      such as role prioritization (Stryker, 1968), one can presume that teachers who
      are tasked with teaching physical education and another school subject may
      experience some level of role conflict.

PMID- 29648928
TI  - An Optimistic Outlook Creates a Rosy Past: The Impact of Episodic Simulation on
      Subsequent Memory.
AB  - People frequently engage in future thinking in everyday life, but it is unknown
      how simulating an event in advance changes how that event is remembered once it
      takes place. To initiate study of this important topic, we conducted two
      experiments in which participants simulated emotional events before learning the
      hypothetical outcome of each event via narratives. Memory was assessed for
      emotional details contained in those narratives. Positive simulation resulted in
      a liberal response bias for positive information and a conservative bias for
      negative information. Events preceded by positive simulation were considered more
      favorably in retrospect. In contrast, negative simulation had no impact on
      subsequent memory. Results were similar across an immediate and delayed memory
      test and for past and future simulation. These results provide novel insights
      into the cognitive consequences of episodic future simulation and build on the
      optimism-bias literature by showing that adopting a favorable outlook results in
      a rosy memory.

PMID- 29648929
TI  - Composition and Diversity of Communities of Dactylogyrus spp. In Wild and Farmed
      Goldfish Carassius auratus.
AB  - Species composition and diversity of dactylogyrids were compared on gills of wild
      and cultured goldfish (silver crucian carp) Carassius auratus from 3 naturally
      populated lakes and 3 stocked aquaculture ponds in the Hubei province of China to
      examine the differences in the gill parasite community between these natural and
      farmed waters. Of the 7 Dactylogyrus spp. detected, all were found in lakes and 5
      in ponds, with Dactylogyrus inexpectatus and Dactylogyrus anchoratus being absent
      from ponds. No significant correlation was found between the species richness and
      habitat area or host size, nor was there a significant difference in mean species
      richness between lakes (0.41-0.65) and ponds (0.30-0.76). Brillouin's diversity
      in lakes (0.049-0.067) was higher than that in ponds (0.024-0.046), but not
      significantly so. Although the diversity of parasite communities was higher in
      wild goldfish, higher mean abundance of some Dactylogyrus spp. was found in
      cultured goldfish. Based on Bray-Curtis similarity, it was difficult to
      differentiate parasite communities in lakes from those in ponds at the
      infracommunity level, whereas the 3 lakes and Guanqiao pond differed markedly
      from the remaining 2 ponds at the component community level. Although
      infracommunities differed among waterbodies, no effects of fish length or
      waterbody type were found on infracommunity or component community structure.
      Together, these results suggest that abundance and species richness of
      Dactylogyrus spp. on goldfish in lakes and farm ponds are influenced by habitat
      specific environmental factors.

PMID- 29648930
TI  - Antioxidant and Antimicrobial Effects of Catechin Liposomes on Chinese Dried
      Pork.
AB  - In this study, catechin (CT), catechin liposome (CTL), and alpha-tocopherol (TP)
      were added to Chinese dried pork to achieve a healthy lipid composition. Their
      effectiveness in prevention of lipid oxidation was determined by measuring the
      values of thiobarbituric acid-reactive substances and peroxides. The total viable
      count in samples was used to identify the antimicrobial activities of CT, CTL,
      and TP, and the pH values of the samples were determined. Chinese dried pork with
      antioxidants added at 600 mg/kg was subjected to sensory evaluation.
      Thiobarbituric acid-reactive substance values, peroxide values, and total viable
      counts indicated that CTL significantly enhanced the antioxidant and
      antibacterial effects of CT on Chinese dried pork, especially after storage at
      room temperature for 25 days. Compared with the two other antioxidants, CTL could
      better maintain the pH stability of Chinese dried pork at room temperature.
      Sensory evaluation revealed that the scores of CTL were better than those of CT
      and TP in terms of preserving the color, flavor, tenderness, and overall
      acceptability of Chinese dried pork. Use of CTL in Chinese dried pork had good
      antioxidant and antibacterial effects and maintained color, flavor, and
      tenderness at a relatively stable level, suggesting that CTL could be used as an
      antioxidant in Chinese dried pork to enhance oxidative stability and prolong
      shelf life.

PMID- 29648931
TI  - Contamination by Meat Juice When Shopping for Packages of Raw Poultry.
AB  - Raw poultry products often are contaminated with Salmonella and Campylobacter,
      and these bacteria can be transmitted through meat juice on the packages. An
      observational study was conducted to assess consumer exposure to meat juice
      during shopping and to quantify the transmission of meat juice from poultry
      packages to hands and other surfaces. Ninety-six participants completed the
      shopping study; 402 swabs were collected and analyzed for the presence of meat
      juice by an immunoassay. Overall, meat juice was detected on 61% of poultry
      package surfaces, 34% of shoppers' hands, 41% of grocery bags, 60% of kitchen
      surfaces, and 51% of food item surfaces. When meat juice was detected on the
      purchased poultry packages, the chance of the meat juice being on the shopper's
      hands, grocery bags, food items, and kitchen surfaces was significantly higher (
      P < 0.005) compared with packages on which meat juice was not present. Shoppers
      who had poultry wrapped separately during checkout had a significantly lower ( P
      < 0.05) chance of meat juice on the food items. However, using plastic bags and
      wrapping poultry separately did not significantly reduce the likelihood of meat
      juice on kitchen surfaces at home due to consumers' practices of repackaging
      before storage. Results suggested that the transfer of meat juice through direct
      contact with the poultry packages is a major concern during shopping and should
      be prevented.

PMID- 29648932
TI  - Response Surface Methodology for Salmonella Inactivation during Extrusion
      Processing of Oat Flour.
AB  - An increase in the number of foodborne outbreaks and recalls due to Salmonella in
      low-moisture foods has resulted in the need for the development and validation of
      process controls to ensure their microbiological safety. Furthermore, the Food
      Safety Modernization Act Preventive Controls for Human Food final rule requires
      food processors to validate their process controls to ensure food safety. The
      objective of this study was to develop a response surface model to predict
      Salmonella inactivation in oat flour, as affected by moisture, fat content, screw
      speed, and temperature. Oat flour was adjusted to different moisture (14 to 26%
      wet basis) and fat (5 to 15% [w/w]) contents and was then inoculated with a five
      strain cocktail of Salmonella. Inoculated material was extruded through a single
      screw extruder running at different screw speeds (75 to 225 rpm) and temperatures
      (65 to 85 degrees C), without a die. Once steady-state conditions were attained,
      extruded samples were collected, cooled, and stored under refrigeration, and
      Salmonella survivors were enumerated. A split-plot central composite second-order
      response surface design was used, with the central point replicated six times.
      Temperature showed a significant ( P < 0.0005) positive effect on microbial
      reduction. Moisture content showed significant linear ( P = 0.0014) and quadratic
      ( P = 0.0005) effects, whereas higher fat content showed a significant ( P <
      0.0001) protective effect on Salmonella destruction. The screw speed did not play
      a major role in inactivating Salmonella, but it had a significant ( P = 0.0004)
      interactive effect with temperature. Results indicated that a >5.5-log reduction
      was achieved in oat flour extruded at a temperature above 85 degrees C at all
      moisture and fat contents evaluated at a screw speed of 150 rpm. The developed
      response surface model can be used to identify the extrusion process conditions
      to achieve a desired reduction of Salmonella based on the moisture and fat
      contents of the product.

PMID- 29648934
TI  - Understanding Prediabetes in a Medicare Advantage Population Using Data Adaptive
      Techniques.
AB  - The objective was to identify individuals with undiagnosed prediabetes from
      administrative data using adaptive techniques. The data source was a national
      Medicare Advantage Prescription Drug (MAPD) plan administrative data set. A
      retrospective, cross-sectional study developed and evaluated data adaptive
      logistic regression, decision tree, neural network, and ensemble predictive
      models for metabolic syndrome and prediabetes using 3 mutually exclusive cohorts
      (N = 279,903). The misclassification rate (MCR), average squared error (ASE), c
      statistics, sensitivity (SN), and false positive (FP) rates were compared to
      select the final predictive models. MAPD individuals with continuous enrollment
      from 2013 to 2014 were included. Metabolic syndrome and prediabetes were defined
      using clinical guidelines, diagnosis, and laboratory data. A total of 512
      variables identified through subject matter expertise in addition to utilizing
      all data available were evaluated for the modeling. The ensemble model
      demonstrated better discrimination (c-statistics, MCR, and ASE of 0.83, 0.24, and
      0.16, respectively), high SN, and low FP rate in predicting metabolic syndrome
      than the individual data adaptive modeling techniques. Logistic regression
      demonstrated better discrimination (c-statistics, MCR, and ASE of 0.67, 0.13, and
      0.11 respectively), high SN, and low FP rate in predicting prediabetes than the
      other adaptive modeling techniques or ensemble methods. The scored data predicted
      prediabetes in 44% of the MAPD population, which is comparable to 2005-2006
      National Health and Nutrition Examination Survey prediabetes rates of 41%. The
      logistic regression model demonstrated good performance in predicting undiagnosed
      prediabetes in MAPD individuals.

PMID- 29648933
TI  - Influence of Body Position on Shoulder and Trunk Muscle Activation During
      Resisted Isometric Shoulder External Rotation.
AB  - BACKGROUND: External rotation (ER) strengthening of the shoulder is an integral
      component of rehabilitative and preventative programs for overhead athletes. A
      variety of shoulder ER strengthening exercises are reported, including those
      intended to integrate the core musculature. The purpose of this study was to
      examine ER torque and electromyographic (EMG) activation of shoulder and trunk
      muscles while performing resisted isometric shoulder ER in 3 positions (standing,
      side lying, and side plank). HYPOTHESIS: Significantly greater force and shoulder
      muscle activation would be generated while side lying given the inherent
      stability of the position, and greater trunk muscle activation would be generated
      in the less stable plank position. STUDY DESIGN: Quasi-experimental repeated
      measures study. LEVEL OF EVIDENCE: Level 5. METHODS: A convenience sample of 25
      healthy overhead recreational athletes (9 men, 16 women) participated in this
      study. EMG electrodes were placed on the infraspinatus, posterior deltoid, middle
      trapezius, multifidi, internal obliques, and external obliques. EMG signals were
      normalized to a maximal isometric contraction. Participants performed resisted
      isometric ER in standing, side-lying, and side plank positions. Results were
      analyzed using a repeated-measures analysis of variance with post hoc Bonferroni
      corrections (alpha = 0.05). RESULTS: There was no significant difference in ER
      torque between positions (alpha = 0.05). A significant difference in EMG activity
      of shoulder and trunk musculature between positions was found in 7 of the 8
      muscles monitored. Significantly greater EMG activity in the infraspinatus,
      middle trapezius, and the nondominant external and internal obliques was found in
      the side plank position as compared with standing and side lying. CONCLUSION:
      While there was no difference in ER torque between the 3 exercise positions, EMG
      activity of the shoulder and trunk muscles was dependent on body position.
      CLINICAL RELEVANCE: If a clinician is seeking to integrate trunk muscle
      activation while performing shoulder ER strengthening, the side plank position is
      preferred as compared with standing or side lying.

PMID- 29648935
TI  - Episiotomy and perineal tear risk factors in a group of 4493 women.
AB  - Episiotomy belongs to the most frequent procedures carried out during delivery.
      Performing episiotomy should be reduced as there is scientific evidence
      indicating that it can cause pain, sexual problems, and serious, long-term health
      consequences. The aim of the researchers is to identify factors associated with
      episiotomy and the perineal tear. Analyses were performed using a model of a
      logistic regression. The study involved 4493 women. The episiotomy risk was
      related to: a birth weight exceeding 3500 grams, an instrumental delivery by
      means of forceps or vacuum extraction. The decrease of episiotomy rate increased
      the rate of perineal tear of first and second degree. The study has shown that
      episiotomy protects women from third- and fourth-degree perineal tear.

PMID- 29648936
TI  - The Importance of Adolescents' Participation in Organized Sport According to
      VO2peak: A Longitudinal Study.
AB  - : Research from several countries has documented a decline in physical activity
      (PA) levels and in participation in organized sport with increasing age,
      indicating that organized sport may be of importance to adolescents'
      cardiorespiratory fitness (CRF). PURPOSE: The purpose of this study was to
      examine how regular participation in organized and unorganized PA affected the
      development of adolescents' CRF (peak oxygen consumption [VO2peak]), when
      controlled for sex interaction. METHOD: Data on direct measures of VO2peak and
      participation in organized PA among adolescents organized into 3 groups
      (participation in organized sport, participation in unorganized PA, and no weekly
      PA) were collected from 76 students (39 boys and 37 girls), when they were aged
      14 and 19 years old. RESULTS: Statistically significant differences were found
      between VO2peak values in the 3 groups at both 14 years of age, F(2, 73) = 7.16,
      p < .05, n2 = .170, and 19 years of age, F(2, 73) = 14.00, p < .05, n2 = .300,
      independent of sex at both 14 and 19 years of age, F(2, 73) = 0.05, p > .05, n2 =
      .02, and F(2, 73) = 0.05, p > .05, n2 = .00. Adolescents participating in
      organized sport also had statistically significantly higher VO2peak values than
      adolescents participating in unorganized PA and those with no weekly PA, at both
      14  and 19 years of age. CONCLUSION: From a health perspective, in terms of CRF,
      the findings highlight the importance of encouraging adolescents to participate
      in organized sport and to refrain from dropping out of organized sport programs.

PMID- 29648937
TI  - Endothelial Wound Repair of the Organ-Cultured Porcine Corneas.
AB  - PURPOSE: To assess whether injured porcine endothelium of small and large
      corneoscleral disc differ in its reparative/regenerative capacity under various
      conditions of organ culture storage. MATERIAL AND METHODS: 166 paired porcine
      corneas were trephined to obtain tissues with diameter 12.0 mm and 17.5 mm (with
      area neighboring endothelial periphery). In tested discs, central endothelium was
      mechanically wounded. Density of live endothelial cells (LECD), percentage of
      dead cells (%DC), coefficient of variation and cell hexagonality were assessed in
      central and paracentral endothelium following 5- or 9-day incubation in medium
      with 2% or 10% fetal bovine serum. The parameters were assessed also in fresh and
      intact cultured discs. Dead endothelial cells (EC) were visualized by trypan
      blue, cell borders by Alizarin Red S dye. Endothelial imprints were immunoassayed
      for the proliferation marker Ki-67 and the nucleolar marker fibrillarin. RESULTS:
      In fresh corneas, the LECD/mm2 (mean +/- standard deviation) were 3998.0 +/-
      215.4 (central area) and 3888.2 +/- 363.1 (paracentral area). Only the length of
      storage had significant effect on wound repair. Lesion was repaired partially
      after 5-day and fully after 9-day cultivation. After 9-day storage in medium with
      10% serum, the mean LECD detected in small discs were 2409.4 +/- 881.8 (central
      area) and 3949.5 +/- 275.5 (paracentral area) and in large discs the mean LECD
      were 2555.0 +/- 347.0 (central area) and 4007.5 +/- 261.2 (paracentral area). Ki
      67 showed cell proliferation associated with healing of EC of both large and
      small corneas. CONCLUSIONS: The lesions were completely repaired within 9 days of
      storage. Presence of the area, where stem cells appear to be located, contributes
      to stimulation of endothelial reparation less than serum concentration and time
      of culture. Both cell migration and proliferation contribute to the wound repair.

PMID- 29648938
TI  - Novel assessment tool for coronary artery disease severity during screening
      mammography.
AB  - Breast arterial calcifications (BACs) are common findings on mammography which
      are associated with an increased risk of the coronary artery disease (CAD). Our
      aim in the current study was to design measurement instruments of CAD prediction,
      with or without BACs, and its discriminatory validity in the diagnosis of CAD
      (expressed by Syntax score) in women. This was observational, prospective study
      in the women cohort which underwent mammography and angiography. In this study,
      we have demonstrated that the total 'Breast Arterial Calcification and Coronary
      Artery Disease Scale' was good additional diagnostic tool for detection of
      patients with severe CAD.

PMID- 29648939
TI  - Reversal of Schistosome Resistance In Biomphalaria glabrata By Heat Shock May Be
      Dependent On Snail Genotype.
AB  - Several genes have recently been shown to affect the innate resistance of
      laboratory strains of Biomphalaria glabrata to infection with Schistosoma
      mansoni, including Hsp90, the expression of which following a brief exposure to
      elevated temperature can interfere with resistance in juvenile BS-90 snails.
      Because a prior study failed to see a similar effect in adult snails, juvenile BS
      90 snails were exposed to 10 or 50 miracidia following a 4.5 to 6 hr incubation
      at 33 or 37 C. Snails were then monitored for production of secondary sporocysts
      or release of cercariae. In addition, snails exposed to 33 C were examined
      histologically between 1 and 15 days post exposure (DPE) to 30 miracidia to
      assess the fate of primary sporocysts. Other than elevated numbers of viable
      primary sporocysts in the tissues of heat shocked snails at 3 DPE, no
      statistically significant effect of elevated temperature was observed. This
      discrepancy with regard to prior studies is hypothesized to result from genetic
      divergence in different laboratory colonies of the same strain of snail.

PMID- 29648940
TI  - Transfer of primary aromatic amines from coloured paper napkins into four
      different food matrices and into cold water extracts.
AB  - The aim of this study was to compare the transfer of primary aromatic amines
      (PAAs) from napkins into cold water extract (CWE) with transfer into four
      different food matrices. An HPLC-MS/MS multi-analyte method for quantification of
      26 PAAs in CWE was validated and applied. In addition, the method was validated
      for seven different PAAs in four different food matrices (cucumber, rice, pickled
      gherkin and butter cookie) representing wet, dry, acidic and fatty food. The CWEs
      of 12 coloured napkin samples were analysed, and 3 napkins released more than
      0.01 mg kg-1 PAAs into the CWE. These three napkins were chosen for transfer
      testing with food samples. In total, seven different PAAs were quantified in the
      food samples. Results show that the transfer of the tested PAAs into the CWE is
      in most cases comparable to the transfer into the tested food samples. In some
      cases, the CWE overestimates transfer into food, except for the transfer of
      aniline into pickled gherkin, where the CWE underestimates transfer. Therefore,
      the CWE serves as an adequate and certainly not overestimating simulation of
      reality for the tested transfer of PAAs into the food samples.

PMID- 29648941
TI  - Development of an immunochromatographic assay for the beta-adrenergic agonist
      feed additive zilpaterol.
AB  - Zilpaterol is a beta-adrenergic agonist feed additive approved in the United
      States to increase weight gain and improve feed efficiency of cattle. A
      zilpaterol immunochromatographic assay was developed as an economical and user
      friendly rapid detection method for zilpaterol and validated using urine and
      tissue samples derived from animal studies. The assay sensitivity was 1.7-23.2 ng
      g-1 or mL-1 across a variety of feed and animal matrices and did not cross-react
      with clenbuterol or ractopamine. No sample pre-treatment of cattle and sheep
      urine was needed, but horse urine and feed required dilution; skeletal muscle
      required solvent extraction prior to testing. Of 32 incurred sheep urine samples
      tested, zilpaterol content was correctly identified in all but 2 samples. Horse
      urine containing >10 ng mL-1 of incurred zilpaterol residue (n = 48) was
      correctly identified as zilpaterol positive. The assay correctly identified 0-day
      withdrawal sheep muscle samples as zilpaterol positive and the control and longer
      withdrawal day sheep muscle samples as negative. Zilpaterol was demonstrated to
      be stable in horse urine when stored at -20 degrees C for 7 years.

PMID- 29648942
TI  - A phenomenology of informal caregiving for HIV/AIDS in India: Exploring women's
      search for authoritative knowledge, self-efficacy and resilience.
AB  - Women provide informal caregiving across the world and are often expected to
      provide care even when ailing themselves. We explore the lived experience of 33
      impoverished married Indian women living with HIV and caring for their husbands
      and/or children living with HIV. Drawing on concepts of authoritative knowledge
      (AK), self-efficacy and resilience, we found a trajectory that reveals barriers
      to accessing care, yet we also found that women developed strengths and
      resiliency. Women gather information, develop "environ-info," and deliberatively
      weigh AK from health workers, family/friends' advice, and their own experiences.
      Over multiple iterations of this process, they build self-reliance and
      resilience.

PMID- 29648943
TI  - Who SKIPS? Using Temperament to Explain Differential Outcomes of a Motor
      Competence Intervention for Preschoolers.
AB  - PURPOSE: Although motor skill interventions often improve fundamental motor
      skills (FMS) during preschool, the extent of individual children's success in
      development of FMS still varies among children receiving the same intervention.
      Temperament is multifaceted and includes negative affect (high levels of
      frustration or anger), effortful control (focus, self-regulation, and
      concentration), and surgency (energy and activity level). Temperament often
      influences cognitive, social, and behavioral outcomes and may be a significant
      factor in the development of FMS. The purpose of this study was to examine the
      influence of temperament on children's improvement in FMS within a gross motor
      intervention. METHOD: Participants (N = 80; Mage = 55.36 months, SD = 6.99
      months) completed the Test of Gross Motor Development-Second Edition prior to and
      after intervention. Teachers completed the Child Behavior Questionnaire-Very
      Short Form to examine each child's temperament. To account for possibility of a
      Type 1 error, we conducted 6 separate 2 (temperament variable: high, low) * 2
      (treatment: intervention, control) analyses of covariance and examined posttest
      scores for locomotor and object-control skills with pretest scores as covariates
      among participants with high and low surgency, negative affect, and effortful
      control. RESULTS: Results revealed children with low levels of negative affect
      and surgency and high levels of effortful control demonstrated greater gains
      (etap2 = .05-.34) in both locomotor and object-control skills during motor skill
      intervention compared with their peers. CONCLUSION: Providing interventions
      tailored to temperamental profiles could maximize gains in FMS through
      intervention.

PMID- 29648945
TI  - The Asian Citrus Psyllid Host Murraya koenigii Is Immune to Citrus Huanglongbing
      Pathogen 'Candidatus Liberibacter asiaticus'.
AB  - The Asian citrus psyllid (ACP) Diaphorina citri, vector of 'Candidatus
      Liberibacter asiaticus' (CLas), the putative causal agent of citrus Huanglongbing
      (HLB), is controlled by application of insecticides, which, although effective,
      has resulted in serious biological imbalances. New management tools are needed,
      and the technique known as "trap crop" has been attracting attention. A potential
      plant for use as a trap crop in the management of the ACP is Murraya koenigii
      (curry leaf). However, for this plant to be used in the field, it needs to be
      attractive for the vector and must not harbor CLas. To verify the potential of
      curry leaf as trap crop for the management of HLB, we investigated the ability of
      D. citri to transmit CLas to M. koenigii, and to other test plants, including M.
      paniculata (orange jasmine) and cultivar Valencia sweet-orange seedlings. For the
      tests, the insects were reared on a symptomatic CLas-infected plant and allowed
      to feed on the three test plant species. The overall maximum transmission rate
      for the citrus seedlings was 83.3%, and for orange jasmine was 33.3%. Successful
      transmission of CLas by ACP to the curry-leaf seedlings was not observed, and it
      was treated as immune to CLas. Supported by the previous results that M. koenigii
      is attractive for ACP, these results indicate that curry leaf is an excellent
      candidate for use as a trap crop, to improve the management of the insect vector
      and consequently of HLB.

PMID- 29648944
TI  - Parents' concerns regarding the growth characteristics of their adolescents: a
      qualitative inquiry in Iran.
AB  - In recent times, parents have become increasingly concerned, both subjectively
      and objectively, about their adolescents' body height/weight growth. Parent
      adolescent interactions about this issue and the potential socio-psychological
      consequences of such interactions should be considered as an important
      influencing factor on the future of adolescents' sexual and reproductive health.
      To achieve a greater understanding of such concerns, it is necessary to further
      elucidate parents' experiences on this topic, so as to expand the existing
      literature. This study aimed to explain the perceptions of parents' concerns
      regarding their adolescents' growth characteristics in the socio-cultural context
      of Iran as a transitional society. This paper is part of a larger qualitative
      study designed using the Constructivist Grounded Theory Methodology (CGTM). We
      conducted open-ended intensive interviews with eleven parents individually and
      recruited them through purposeful and theoretical sampling from a teaching
      hospital, community, and a primary school in Tehran with theoretical sampling
      variation in terms of teenagers' age, sex, and birth order, place of residence,
      parents' occupation and education, and the self-reported socio-economic status.
      Using the analytical procedures of the CGTM, we performed analyses. In the
      findings, the concept of 'living with constant sense of uncertainty' emerged from
      the subcategories including 'feeling existing and potential concern about
      expected minimum and maximum bio-positions of growth,' 'feeling potential concern
      about biological health consequences,' 'feeling potential concern about the
      emergence of early/late maturity signs,' 'feeling potential concern about
      adolescent's emotional threat,' 'feeling concerned about future employment,
      education, marriage, and fertility,' and 'feeling potential concern about the
      society's view'. These findings suggest that parents are living with a constant
      sense of uncertainty about their teens' growth characteristics throughout the
      transition from adolescence. All stakeholders including parents, health-care
      practitioners and policymakers, and anthropologists/sociologists should be focus
      on such concerns, in order to manage them and their possible socio-psychological
      burdens.

PMID- 29648946
TI  - Changing Host Photosynthetic, Carbohydrate, and Energy Metabolisms Play Important
      Roles in Phytoplasma Infection.
AB  - Phytoplasmas parasitize plant phloem tissue and cause many economically important
      plant diseases. Jujube witches'-broom disease is a destructive phytoplasma
      disease of Chinese jujube (Ziziphus jujuba). To elucidate the influence of
      phytoplasma on host photosynthetic, carbohydrate and energy metabolisms, four
      types of jujube tissues showing disease symptoms with different severity were
      investigated at the structural, physiological, and molecular levels. Quantitative
      real-time PCR and high-performance liquid chromatography results showed that the
      down-regulation of genes related to photosynthesis and the lower contents of
      chlorophyll in diseased leaves. This clearly inhibited the light-harvesting and
      photosystem II activity of photosynthesis; however, overexpression of genes
      related to starch, sucrose and glucose synthesis led to higher contents of these
      carbohydrates. Meanwhile, transmission electron microscopy images revealed that
      dense amounts of phytoplasmas accumulated in the sieve elements of diseased
      petiole phloem, and the structure of the grana and stroma lamellae of
      chloroplasts in the diseased leaves was destroyed. Phytoplasma infection
      inhibited photosynthesis and led to abnormal carbohydrate accumulation in the
      diseased leaves. Furthermore, comparative metabolite analysis indicated that
      phytoplasma infection also stimulated amino acids and energy metabolisms of the
      diseased leaves. Continually inhibiting the photosynthetic process and
      stimulating carbohydrate and energy metabolisms of diseased trees may exhaust
      their nutrients. Our results highlight the importance of changing host
      metabolisms during the pathogenic process.

PMID- 29648947
TI  - Pyramiding for Resistance Durability: Theory and Practice.
AB  - Durable disease resistance is a key component of global food security, and
      combining resistance genes into "pyramids" is an important way to increase
      durability of resistance. The mechanisms by which pyramids impart durability are
      not well known. The traditional view of resistance pyramids considers the use of
      major resistance gene (R-gene) combinations deployed against pathogens that are
      primarily asexual. Interestingly, published examples of the successful use of
      pyramids in the traditional sense are rare. In contrast, most published
      descriptions of durable pyramids in practice are for cereal rusts, and tend to
      indicate an association between durability and cultivars combining major R-genes
      with incompletely expressed, adult plant resistance genes. Pyramids have been
      investigated experimentally for a diversity of pathogens, and many reduce disease
      levels below that of the single best gene. Resistance gene combinations have been
      identified through phenotypic reactions, molecular markers, and challenge against
      effector genes. As resistance genes do not express equally in all genetic
      backgrounds, however, a combination of genetic information and phenotypic
      analyses provide the ideal scenario for testing of putative pyramids. Not all
      resistance genes contribute equally to pyramids, and approaches have been
      suggested to identify the best genes and combinations of genes for inclusion.
      Combining multiple resistance genes into a single plant genotype quickly is a
      challenge that is being addressed through alternative breeding approaches, as
      well as through genomics tools such as resistance gene cassettes and gene
      editing. Experimental and modeling tests of pyramid durability are in their
      infancy, but have promise to help direct future studies of pyramids. Several
      areas for further work on resistance gene pyramids are suggested.

PMID- 29648948
TI  - Recessive Resistance to Bean common mosaic virus Conferred by the bc-1 and bc-2
      Genes in Common Bean (Phaseolus vulgaris) Affects Long-Distance Movement of the
      Virus.
AB  - Recessive resistance to Bean common mosaic virus (BCMV) in common bean (Phaseolus
      vulgaris) is governed by four genes that include one strain-nonspecific helper
      gene bc-u, and three strain-specific genes bc-1, bc-2, and bc-3. The bc-3 gene
      was identified as an eIF4E translation initiation factor gene mediating
      resistance through disruption of the interaction between this protein and the VPg
      protein of the virus. The mode of action of bc-1 and bc-2 in expression of BCMV
      resistance is unknown, although bc-1 gene was found to affect systemic spread of
      a related potyvirus, Bean common mosaic necrosis virus. To investigate the
      possible role of both bc-1 and bc-2 genes in replication, cell-to-cell, and long
      distance movement of BCMV in P. vulgaris, we tested virus spread of eight BCMV
      isolates representing pathogroups I, IV, VI, VII, and VIII in a set of bean
      differentials expressing different combinations of six resistance alleles
      including bc-u, bc-1, bc-12, bc-2, bc-22, and bc-3. All studied BCMV isolates
      were able to replicate and spread in inoculated leaves of bean cultivars
      harboring bc-u, bc-1, bc-12, bc-2, and bc-22 alleles and their combinations,
      while no BCMV replication was found in inoculated leaves of cultivar IVT7214
      carrying the bc-u, bc-2, and bc-3 genes, except for isolate 1755a, which was
      capable of overcoming the resistance conferred by bc-2 and bc-3. In contrast, the
      systemic spread of all BCMV isolates from pathogroups I, IV, VI, VII, and VIII
      was impaired in common bean cultivars carrying bc-1, bc-12, bc-2, and bc-22
      alleles. The data suggest that bc-1 and bc-2 recessive resistance genes have no
      effect on the replication and cell-to-cell movement of BCMV, but affect systemic
      spread of BCMV in common bean. The BCMV resistance conferred by bc-1 and bc-2 and
      affecting systemic spread was found only partially effective when these two genes
      were expressed singly. The efficiency of the restriction of the systemic spread
      of the virus was greatly enhanced when the alleles of bc-1 and bc-2 genes were
      combined together.

PMID- 29648950
TI  - Growing the Soft Robotics Community Through Knowledge-Sharing Initiatives.

PMID- 29648949
TI  - Induced Systemic Resistance Against Citrus Canker Disease by Rhizobacteria.
AB  - Citrus canker, caused by Xanthomonas citri subsp. citri, is an important citrus
      disease that causes significant economic losses worldwide. All commercial citrus
      varieties are susceptible to citrus canker. Currently, chemical control with
      copper based products is the main approach to control X. citri subsp. citri
      dispersal and plant colonization. However, extensive use of copper compounds can
      result in copper-resistant strains and cause adverse effects on the environment.
      Alternatives to chemical control involve the activation of citrus immunity to
      control the disease. Here, we investigated the ability of multiple rhizobacteria
      to induce a systemic defense response in cultivar Duncan grapefruit. Burkholderia
      territorii strain A63, Burkholderia metallica strain A53, and Pseudomonas
      geniculata strain 95 were found to effectively activate plant defense and
      significantly reduce symptom development in leaves challenged with X. citri
      subsp. citri. In the priming phase, root application of P. geniculata induced the
      expression of salicylic acid (SA)-signaling pathway marker genes (PR1, PR2, PR5,
      and salicylic acid carboxyl methyltransferase [SAM-SACM]). Gene expression
      analyses after X. citri subsp. citri challenge showed that root inoculation with
      P. geniculata strain 95 increased the relative levels of phenylalanine ammonia
      lyase 1 and SAM-SACM, two genes involved in the phenylpropanoid pathway as well
      as the biosynthesis of SA and methyl salicylate (MeSA), respectively. However,
      hormone analyses by UPLC-MS/MS showed no significant difference between SA in P.
      geniculata-treated plants and control plants at 8 days post-beneficial bacteria
      root inoculation. Moreover, P. geniculata root-treated plants contained higher
      reactive oxygen species levels in aerial tissues than control plants 8 days post
      treatment application. This study demonstrates that rhizobacteria can modulate
      citrus immunity resulting in a systemic defense response against X. citri subsp.
      citri under greenhouse conditions.

PMID- 29648951
TI  - Design of a Lightweight Soft Robotic Arm Using Pneumatic Artificial Muscles and
      Inflatable Sleeves.
AB  - As robots begin to interact with humans and operate in human environments, safety
      becomes a major concern. Conventional robots, although reliable and consistent,
      can cause injury to anyone within its range of motion. Soft robotics, wherein
      systems are made to be soft and mechanically compliant, are thus a promising
      alternative due to their lightweight nature and ability to cushion impacts, but
      current designs often sacrifice accuracy and usefulness for safety. We,
      therefore, have developed a bioinspired robotic arm combining elements of rigid
      and soft robotics such that it exhibits the positive qualities of both, namely
      compliance and accuracy, while maintaining a low weight. This article describes
      the design of a robotic arm-wrist-hand system with seven degrees of freedom
      (DOFs). The shoulder and elbow each has two DOFs for two perpendicular rotational
      motions on each joint, and the hand has two DOFs for wrist rotations and one DOF
      for a grasp motion. The arm is pneumatically powered using custom-built McKibben
      type pneumatic artificial muscles, which are inflated and deflated using binary
      and proportional valves. The wrist and hand motions are actuated through
      servomotors. In addition to the actuators, the arm is equipped with a
      potentiometer in each joint for detecting joint angle changes. Simulation and
      experimental results for closed-loop position control are also presented in the
      article.

PMID- 29648952
TI  - Reliability and validity evidence of the Assessment of Language Use in Social
      Contexts for Adults (ALUSCA).
AB  - BACKGROUND: The appropriate use of language in context depends on the speaker's
      pragmatic language competencies. A coding system was used to develop a specific
      and adult-focused self-administered questionnaire to adults who stutter and
      adults who do not stutter, The Assessment of Language Use in Social Contexts for
      Adults, with three categories: precursors, basic exchanges, and extended
      literal/non-literal discourse. This paper presents the content validity, item
      analysis, reliability coefficients and evidences of construct validity of the
      instrument. METHODS: Content validity analysis was based on a two-stage process:
      first, 11 pragmatic questionnaires were assessed to identify items that probe
      each pragmatic competency and to create the first version of the instrument;
      second, items were assessed qualitatively by an expert panel composed by adults
      who stutter and controls, and quantitatively and qualitatively by an expert panel
      composed by clinicians. A pilot study was conducted with five adults who stutter
      and five controls to analyse items and calculate reliability. Construct validity
      evidences were obtained using the hypothesized relationships method and factor
      analysis with 28 adults who stutter and 28 controls. RESULTS: Concerning content
      validity, the questionnaires assessed up to 13 pragmatic competencies.
      Qualitative and quantitative analysis revealed ambiguities in items construction.
      Disagreement between experts was solved through item modification. The pilot
      study showed that the instrument presented internal consistency and temporal
      stability. Significant differences between adults who stutter and controls and
      different response profiles revealed the instrument's underlying construct.
      CONCLUSION: The instrument is reliable and presented evidences of construct
      validity.

PMID- 29648953
TI  - Field Sanitation in U.S. Agriculture: Evidence from NAWS and Future Data Needs.
AB  - OBJECTIVES: We studied relationships between demographic and work-related
      characteristics and exposure to health-related risk associated with field
      sanitation within the population of U.S. farmworkers while critically examining
      adequacy of existing data toward understanding patterns. METHODS: We used
      statistical and econometric large-sample data methods to analyze correlations
      between observable variables and access to field sanitation as measured by
      responses to the nationally and regionally representative National Agricultural
      Workers Survey (NAWS). RESULTS: Analysis suggests that field sanitation risk is
      relatively low on U.S. farms, especially in the most current periods, though
      there is regional variation. A number of socioeconomic characteristics are
      predictive of remaining gaps in access to basic field sanitation. We found that
      men, workers with less education, workers who do not speak English well, and
      those from Mexico are systematically more likely to lack access to field
      sanitation than are other workers, all else equal. We also found associations
      with job-related characteristics. CONCLUSION: We conclude that regulatory
      standards do not affect all workers equally and that field sanitation risk for
      some workers has continued though the current period. Basic sanitation
      definitions provided in available data are limited and may not reflect the true
      extent of risk associated with the incomplete nature of field sanitation access.
      This motivates the importance of continued study of field sanitation and of
      targeted public policies.

PMID- 29648954
TI  - What Happens to the Farm? Australian Farmers' Experiences after a Serious Farm
      Injury.
AB  - OBJECTIVES: To investigate the experiences of farmers on returning to farming
      following a serious farm-related injury. METHODS: Patients who had sustained
      major trauma on a farm in Victoria, Australia, were identified using the
      Victorian State Trauma Registry (VSTR). In depth, semistructured phone interviews
      were conducted with 31 participants. Interview data were subjected to thematic
      analysis to identify important recurring themes. Interviews continued until data
      saturation was achieved. RESULTS: Interviewees included self-employed full-time
      farmers, part-time farmers with a supplementary income, and agricultural
      employees. Analysis of participant responses connected to returning to farming
      after a serious farm-related injury identified five major interconnected themes:
      (i) effect on farm work, (ii) farming future, (iii) safety advocacy, (iv) changes
      to farming practices, and (v) financial ramifications. CONCLUSION: Farmers who
      have sustained a serious farm-related injury are an important resource; their
      experiences and perspectives could assist in the development of educational and
      transitional support services from recovery back to working at a preinjury level,
      while ensuring farming production is sustainable during this period. Furthermore,
      farm safety programs can be enhanced by the engagement of farmers, such as
      participants in this study as advocates for improved farm safety practices.

PMID- 29648955
TI  - Investigation of UK Farmer Go/No-Go Decisions in Response to Tractor-Based Risk
      Scenarios.
AB  - OBJECTIVES: Tractors are a source of injury and fatality in agriculture. Despite
      this farmers continue to engage in risk-taking behaviors, including operating
      tractors without appropriate equipment. In order to change behaviors and
      attitudes toward safety, it is important to understand how farmers approach
      different types of risk relevant to tractor use. The current study used a
      qualitative approach to investigate farmer perception of four types of tractor
      based risk related to self, equipment, lack of safety features, and environment.
      METHOD: A sample of 148 farmers from the United Kingdom and Ireland was recruited
      from farming forums to take part in an online scenario-based qualitative study.
      Participants were presented with 12 tractor-based scenarios, three from each
      category of risk, and asked to indicate if they would proceed to use the tractor
      (go) or not (no-go), then report their reasoning. Thematic analysis was used to
      identify data patterns. RESULTS: Farmers appeared to assess the consequences of
      risk in broader terms than the risk of injury to themselves; they also evaluated
      risk in terms of potential costs (e.g., repair bill) and losses (e.g., delay).
      Analysis indicated that financial risk was considered with more caution than
      personal risk in many cases. Farmers also considered usability, such as the
      functionality of tractor seat belts, indicating the importance of ensuring all
      safety equipment is fit for purpose. CONCLUSION: The management of agricultural
      risk should consider farmer priorities (such as financial costs) in order to
      develop effective messaging that focuses on those priorities, with the aim of
      reducing risk-taking behaviors.

PMID- 29648956
TI  - Chronic Health Risks in Commercial Fishermen: A Cross-Sectional Analysis from a
      Small Rural Fishing Village in Alaska.
AB  - OBJECTIVES: The purpose of this study is to evaluate chronic health risks before
      and during the fishing season in a sample of commercial fishermen, addressing the
      NIOSH priority of Total Worker HealthTM. METHODS: Gillnet license holders in
      Cordova, Alaska (n = 607) were contacted to participate in a preseason survey
      (March 2015) assessing health behaviors. A mid-season survey (July 2015) was also
      conducted. Physical exams and additional assessments were performed on a subset
      of these fishermen. RESULTS: Sixty-six fishermen participated in the preseason
      survey and 38 participated in the mid-season survey. The study population was
      overwhelmingly white males with an average age of 49. The average BMI was 27 with
      70% of the participants overweight or obese. Nearly 80% of the sample considered
      their health good or better. Participants reported longer working hours, less
      sleep, and less aerobic exercise during the fishing season (P < .05). FitBitTM
      monitoring (n = 8) confirmed less sleep and fewer steps during fishing season. In
      one exam (n = 20), 80% of participants showed measured hearing loss at 4 kz
      (conversation range), and 70% had one or more upper extremity disorders,
      including 40% with rotator cuff tendonitis. CONCLUSIONS: The prevalence of
      hearing loss, upper extremity disorders, and sleep apnea risk factors were higher
      than in the general population both before and during the fishing season.
      Occupational factors including exposure to noise, the upper extremity demands of
      gillnetting, and long working hours while fishing exacerbate these chronic health
      conditions. Health promotion programs targeted toward these conditions may
      present opportunities for improving total worker health.

PMID- 29648957
TI  - Asthma among Household Youth on Racial Minority Operated Farms-United States,
      2008.
AB  - OBJECTIVES: Youth on farms are at risk for injuries and illnesses, including
      asthma, which continues to disproportionately affect minority groups. METHODS:
      For this study, the 2008 Minority Farm Operator Childhood Agricultural Injury
      Survey (M-CAIS) data were used to estimate the prevalence of asthma among youth
      aged 0-19 years living on racial minority-operated farms. Youth were considered
      to have a lifetime diagnosis of asthma based on an affirmative response to the
      question "Has he/she ever been diagnosed as having asthma by a health
      professional?" RESULTS: In 2008, of the estimated 37,400 youth (0-19 years) who
      lived on racial minority operated farms, 11% had asthma. Asthma prevalence was
      highest among males (13%) and youth 10-19 years of age (12%). Asthma prevalence
      among youth varied by race, ranging from 13% among household youth living on
      Black/African American operated farms to 7% among youth living on Asian/Native
      Hawaiian/Pacific Islander operated farms. In 2008, nearly half (46%) of household
      youth (0-19 years) worked on the farm. The odds of having asthma were higher
      among working youth compared with non-working youth (POR, 1.5; 95% CI: 1.3-1.8).
      CONCLUSION: Disparities in asthma among youth living or working on racial
      minority-operated farms were observed. These findings may assist agricultural
      safety and health researchers, practitioners, and educators in identifying and
      designing targeted interventions to reduce asthma burden among youth on racial
      minority-operated farms.

PMID- 29648958
TI  - Effect of Time Elapsed since Last Pruner Maintenance on Upper-Extremity
      Biomechanics during Manual Flower Cutting.
AB  - OBJECTIVE: Manual flower cutting imposes large biomechanical demands on workers'
      upper extremities. Solutions are required to reduce these demands. This study
      investigated the effect of time elapsed since the last pruner maintenance on the
      biomechanical demands of the upper extremities during flower-cutting operations.
      METHODS: Sixteen experienced workers were recruited. All workers performed flower
      cutting 1, 15, and 30 days after standard pruner maintenance, including cleaning,
      adjustment, and sharpening. The outcomes included kinematics of the wrist, elbow,
      and forearm; muscular activity of the extensor carpi radialis, extensor carpi
      ulnaris, flexor carpi radialis, flexor carpi ulnaris, biceps and medium deltoids
      of the dominant arm; and self-reported effort. RESULTS: On average across
      muscles, a 15-day delay (from 1 to 15 and from 15 to 30 days) in the execution of
      pruner maintenance increased over 8% the median recorded muscular activity as
      measured by the percentage of the maximum voluntary contraction of the root mean
      square signal. An increase in time since last pruner maintenance resulted in an
      increase in the 90th percentile pronation-supination posture (larger excursion
      toward pronation); the median and the 90th percentile velocity of the wrist and
      elbow; and the 90th percentile acceleration in the pronation-supination
      direction. There was an increase in perceived effort as measured by a Borg scale
      as time since last maintenance increased from 1 to 15 days. CONCLUSION:
      Increasing the frequency of pruner maintenance procedures can effectively reduce
      workers' mechanical exposures during manual flower-cutting operations. Companies
      should implement daily maintenance programs considering their implementation
      capacity and expected benefits.

PMID- 29648959
TI  - The Feasibility of Telephone-Administered Cognitive Testing in Individuals 1 and
      2 Years after Inpatient Rehabilitation for Traumatic Brain Injury.
AB  - Traumatic brain injury (TBI) often results in cognitive impairment, and
      trajectories of cognitive functioning can vary tremendously over time across
      survivors. Traditional approaches to measuring cognitive performance require face
      to-face administration of a battery of objective neuropsychological tests, which
      can be time- and labor-intensive. There are numerous clinical and research
      contexts in which in-person testing is undesirable or unfeasible, including
      clinical monitoring of older adults or individuals with disability for whom
      travel is challenging, and epidemiological studies of geographically dispersed
      participants. A telephone-based method for measuring cognition could conserve
      resources and improve efficiency. The objective of this study is to examine the
      feasibility and usefulness of the Brief Test of Adult Cognition by Telephone
      (BTACT) among individuals who are 1 and 2 years post-moderate-to-severe TBI. A
      total of 463 individuals participated in the study at Year 1 post-injury, and 386
      participated at Year 2. The sample was mostly male (73%) and white (59%), with an
      average age of (mean +/- standard deviation) 47.9 +/- 20.9 years, and 73%
      experienced a duration of post-traumatic amnesia (PTA) greater than 7 days. A
      majority of participants were able to complete the BTACT subtests (61-69% and 56
      64% for Years 1 and 2 respectively); score imputation for those unable to
      complete a test due to severity of cognitive impairment yields complete data for
      74-79% of the sample. BTACT subtests showed expected changes between Years 1-2,
      and summary scores demonstrated expected associations with injury severity,
      employment status, and cognitive status as measured by the Functional
      Independence Measure. Results indicate it is feasible, efficient, and useful to
      measure cognition over the telephone among individuals with moderate-severe TBI.

PMID- 29648960
TI  - Running out of time: exploring women's motivations for social egg freezing.
AB  - OBJECTIVE: Few qualitative studies have explored women's use of social egg
      freezing. Derived from an interview study of 31 participants, this article
      explores the motivations of women using this technology. METHODS: Semi-structured
      interviews were conducted with 31 users of social egg freezing resident in UK (n
      = 23), USA (n = 7) and Norway (n = 1). Interviews were face to face (n = 16),
      through Skype and Facetime (n = 9) or by telephone (n = 6). Data were analyzed
      using interpretive thematic analysis. RESULTS: Women's use of egg freezing was
      shaped by fears of running out of time to form a conventional family,
      difficulties in finding a partner and concerns about "panic partnering", together
      with a desire to avoid future regrets and blame. For some women, use of egg
      freezing was influenced by recent fertility or health diagnoses as well as
      critical life events. A fifth of the participants also disclosed an underlying
      fertility or health issue as affecting their decision. CONCLUSION: The study
      provides new insights in to the complex motivations women have for banking eggs.
      It identifies how women's use of egg freezing was an attempt to "preserve
      fertility" in the absence of the particular set of "life conditions" they
      regarded as crucial for pursuing parenthood. It also demonstrates that few women
      were motivated by a desire to enhance their career and that the boundaries
      between egg freezing for medical and for social reasons may be more porous than
      first anticipated.

PMID- 29648961
TI  - Consensual Nonmonogamy in Pregnancy and Parenthood: Experiences of Bisexual and
      Plurisexual Women With Different-Gender Partners.
AB  - The current study constitutes a qualitative investigation of experiences with and
      perceptions of consensual nonmonogamy (CNM) among a sample of 21 bisexual and
      plurisexual women with different-gender partners. Participants from
      Massachusetts, USA, and Toronto, Canada, were interviewed four times during
      pregnancy and the postpartum period. Using an inductive qualitative approach, we
      found participants were selective about CNM disclosure, and generally
      apprehensive about stigma surrounding CNM involvement. Additionally, results
      emphasize the importance of communication and highlight the range of barriers to
      and benefits of CNM endorsed by these parents. Directions for future research and
      implications for practitioners are discussed.

PMID- 29648962
TI  - Communication of Scientific Uncertainty about a Novel Pandemic Health Threat:
      Ambiguity Aversion and Its Mechanisms.
AB  - Communicating scientific uncertainty about public health threats is ethically
      desirable but challenging due to its tendency to promote avoidance of choice
      options with unknown probabilities-a phenomenon known as "ambiguity aversion."
      This study examined this phenomenon's potential magnitude, its responses to
      different communication strategies, and its mechanisms. In a factorial
      experiment, 2701 adult laypersons in Spain read one of three versions of a
      hypothetical newspaper article describing a pandemic vaccine-preventable disease
      (VPD), but varying in scientific uncertainty about VPD risk and vaccine
      effectiveness: No-Uncertainty, Uncertainty, and Normalized-Uncertainty
      (emphasizing its expected nature). Vaccination intentions were lower for the
      Uncertainty and Normalized-Uncertainty groups compared to the No-Uncertainty
      group, consistent with ambiguity aversion; Uncertainty and Normalized-Uncertainty
      groups did not differ. Ambiguity-averse responses were moderated by health
      literacy and mediated by perceptions of vaccine effectiveness, VPD likelihood,
      and VPD severity. Communicating scientific uncertainty about public health
      threats warrants caution and further research to elucidate its outcomes,
      mechanisms, and management.

PMID- 29648963
TI  - Organizing seniors to protect the health safety net: the way forward.
AB  - Over the past century, the organized voice of seniors has been critical in
      building the U.S. health safety net. Since the 2016 election, that safety net,
      particularly the Medicaid program, is in jeopardy. As we have seen with the rise
      of the Tea Party, senior support for health care programs-even programs that they
      use in large numbers-cannot and should not be taken for granted. This article
      provides a brief history of senior advocacy and an overview of the current senior
      organizing landscape. It also identifies opportunities for building the
      transformational organizing of low-income seniors needed to defend against
      sustained attacks on critical programs. Several suggestions are made, drawn from
      years of work in philanthropy, advocacy, and campaigns, for strengthening the
      ability to organize seniors-particularly low-income seniors-into an effective
      political force advocating for Medicaid and other safety net programs.

PMID- 29648964
TI  - LC-MS/MS-based determination of chloramphenicol, thiamphenicol, florfenicol and
      florfenicol amine in poultry meat from the Punjab-Pakistan.
AB  - A simple, reliable and sensitive liquid chromatography-tandem mass spectrometry
      based confirmatory method was redeveloped and validated for the simultaneous
      determination of chloramphenicol, thiamphenicol, florfenicol and florfenicol
      amine in chicken muscles. The analytes were extracted from minced chicken muscle
      with acetonitrile and ammoniated water mixture. A second extraction with ethyl
      acetate was followed by evaporation and dissolution of the residue in ammoniated
      methanol before defatting with n-hexane. Finally, the extract was further cleaned
      up by dispersive solid phase extraction using C-18 end-capped dispersive
      material. The validation protocol was adapted from the European Commission
      Decision 2002/657/EC and all the performance characteristics were successfully
      satisfied. The recoveries of all the analytes were found to be in the range of
      86.4-108.1% and the precision values, within day and between days, ranged from
      2.7% to 11% and 4.4% to 16.3%, respectively. The method was tested in various
      incurred samples and applied to analyse a wide range of random poultry market
      samples (n = 120) collected from three cities of the Punjab, Pakistan.
      Chloramphenicol and florfenicol residues were detected at low levels in less than
      11% of the samples. Chloramphenicol was detected only in 4 samples with the
      concentration range of 0.17-0.477 ug kg-1, whereas the levels of
      florfenicol/florfenicol amine residues detected in 9 samples ranged from 8.7 to
      32.8 ug kg-1. Moreover, most of the florfenicol residues were identified as
      tissue bound, extractable only after strong acid hydrolysis.

PMID- 29648965
TI  - Influence of the Perceived Infidelity of Online Sexual Activities (OSAs) on OSA
      Experiences Among Chinese Heterosexual Individuals in Committed Relationships.
AB  - Previous studies have revealed that many individuals in settled relationships
      engage in online sexual activities (OSAs). Considering this, this study examined
      the influence the perceived infidelity of OSA has on the OSA experiences of
      individuals in such committed relationships. OSAs involve viewing sexually
      explicit material, seeking sexual partners, cybersex, and flirting. Taking these
      specific activities, we measured perceived infidelity concerning OSAs by asking
      our participants (N = 301) to select either "yes" or "no" in regard to whether
      they believed each constituted an infidelity. Further, the participants also
      mentioned if they had engaged in an OSA within the past 12 months and whether
      they considered engaging in OSA in general as an infidelity. Our results
      indicated that men are less likely to perceive OSAs as infidelities, and also
      that they engage more frequently than women in all subtypes of OSA. More
      specifically, individuals who did not perceive OSAs to be infidelities engaged in
      more sexual-partner seeking, cybersex, and flirting than their counterparts.
      Furthermore, perceived infidelity was found to mediate the relationship between
      gender and OSA experiences. The findings indicate that perceived infidelity for
      OSA shapes OSA experiences and contributes to gender differences in terms of
      opinions on and engagement with OSAs.

PMID- 29648966
TI  - Kindergarteners' Narrative Competence Across Tasks and Time.
AB  - The authors investigated children's narrative competence by analyzing the
      development of the reciprocal relationship between storytelling and story
      retelling performances over a school year through a cross-lagged panel design.
      The participants in this study were 170 Italian kindergarten pupils (M age = 4.98
      +/- 0.31 years). Children were asked to produce oral narratives in two different
      tasks: a storytelling and a story retelling task. Narrative competence was
      assessed in terms of structure and coherence. The cross-lagged panel analyses
      showed that both storytelling and story retelling tasks are stable constructs,
      but they differ in the emphasis on coherence. Data confirmed the pivotal role
      played by storytelling as a task, and structure as a component in fostering the
      development of children's narrative competence. Overall, results from this study
      suggest that storytelling and story retelling are tasks that involve interrelated
      but not overlapping processes, and trigger different aspects of narrative
      competence.

PMID- 29648967
TI  - Calcium and Magnesium Contents in Three Hypericum L. Species from Turkey.
AB  - Hypericum L. (Hypericaceae), which has 400 species in the world and 96 species in
      Turkey, has grown in Europe, Asia, North Africa, and America. Hypericum species
      have antidepressant, analgesic, spazmolytic, anti-inflammatory, antiviral, and
      wound healing effects. The purpose of this study was to analyze the magnesium
      (Mg) and calcium (Ca) contents of three Hypericum species (Hypericum perforatum
      L., Hypericum triquetrifolium Turra, and Hypericum empetrifolium Willd.)
      collected from the western part of Turkey. Analyses were done by atomic
      absorption spectrometer using convenient conditions. Mg and Ca concentrations
      were determined in three Hypericum species. Mg levels were determined as 1.053 +/
      0.09, 0.792 +/- 0.06, and 0.798 +/- 0.17 mg.g-1 and Ca levels were determined as
      0.573 +/- 0.19, 0.433 +/- 0.06, and 0.329 +/- 0.005 mg.g-1 in H. perforatum L.,
      H. triquetrifolium Turra, and H. empetrifolium Willd., respectively. The sedative
      effect of the drug is compensated with the metal concentration observed from the
      analysis, which shows that high Mg levels overlap with the sedative effect of the
      drug.

PMID- 29648968
TI  - Saccharina japonica Extract Suppresses Stemness of Glioma Stem Cells by Degrading
      Epidermal Growth Factor Receptor/Epidermal Growth Factor Receptor Variant III.
AB  - Cancer stem cells, a small subpopulation of cells with stem cell-like
      characteristics found within most solid tumors, are widely reported to be
      responsible for the malignancy of aggressive cancer cells, and targeting these
      cells presents a sound therapeutic strategy for reducing the risk of tumor
      relapse. In the present study, we examined the effects of an extract of
      Saccharina japonica (ESJ) on glioblastoma stem cells (GSCs). Saccharina japonica
      is a member of the Phaeophyceae (brown algae) family, which displays biological
      activities, including antitumor effects. ESJ inhibited the sphere-forming ability
      of GSCs in vitro as evidenced by neurosphere formation and limiting dilution
      assays. Treatment with ESJ partially induced apoptosis, reduced cell
      invasiveness, and sensitized GSCs to ionizing radiation. In addition, ESJ
      inhibited the maintenance of stemness in GSCs by suppressing the expression of
      epidermal growth factor receptor (EGFR)/EGFR variant III (EGFRvIII) and Notch
      intracellular domain. Intriguingly, the observed ESJ-induced suppression also
      appeared to induce the proteasomal degradation of EGFR/EGFRvIII. Our results
      indicate that ESJ could be considered a potent therapeutic adjuvant that targets
      GSCs.

PMID- 29648969
TI  - Lactobacillus curvatus KFP419 and Leuconostoc mesenteroides subsp. mesenteroides
      KDK411 Isolated from Kimchi Ameliorate Hypercholesterolemia in Rats.
AB  - Western-style diets increase the risk for cardiovascular diseases. It is
      suggested that the risk could be prevented by lowering cholesterol concentrations
      in blood. In the present study, hypocholesterolemic effects of the probiotics
      isolated from kimchi (Lactobacillus curvatus KFP419, Leuconostoc
      paramesenteroides KJP421, and Leuconostoc mesenteroide subsp. mesenteroides
      KDK411) were investigated in hypercholesterolemia-induced rats. There was no
      difference in growth performance between the rats fed high cholesterol diet (HCD)
      and normal diet (ND). However, blood total cholesterol, low-density lipoprotein
      cholesterol, and hepatic cholesterol were elevated by the HCD compared to ND, and
      those concentrations were decreased by dietary supplementation of KFP419 and
      KDK411. It was concomitant with an increase in fecal excretion of neutral sterols
      (cholesterol, coprostanol, and coprostanone) in the rats fed HCD compared to ND
      and was even greater with KDK411 supplementation. These findings indicate that
      probiotics L. curvatus KFP419 and L. mesenteroide subsp. mesenteroides KDK411
      isolated from kimchi ameliorate hypercholesterolemia in rats by assimilating and
      excreting cholesterol in feces.

PMID- 29648970
TI  - Posttreatment Effects of Olea Europaea L. Leaf Extract on Carbon Tetrachloride
      Induced Liver Injury and Oxidative Stress in Rats.
AB  - The aim of this study is to examine the therapeutic effects of Olea europaea L.
      leaf extract on carbon tetrachloride (CCl4)-induced liver damage in rats. In the
      experiments, 3- to 4-month-old 28 male Sprague-Dawley rats were divided into four
      groups: control, O. europaea leaf extract, CCl4, and curative. The CCl4 and
      curative groups received CCl4 (0.2 mL/kg) intraperitoneally for 10 days to form
      hepatic injury. O. europaea (80 mg/kg) leaf extract was given orally to the
      curative group dissolved in distilled water the following 14 days. Hepatic and
      antioxidant enzyme levels, p53, caspase 3, lipid peroxidation marker
      malondialdehyde (MDA), and also DNA fragmentation levels were determined to
      establish oxidative stress in hepatic cell damage and its consequences. After
      formation of liver damage, oral administration of the O. europaea significantly
      reduced CCl4-induced elevations of serum alkaline phosphatase, aspartate
      aminotransferase and alanine aminotransferase levels (P < .001), MDA levels of
      both blood (P < .001) and liver tissues (P < .001), DNA fragmentation (P < .001),
      p53 (P < .001), and caspase 3 (P < .001) levels of liver tissues. Also this
      administration in curative group significantly increased CCl4-induced reductions
      of superoxide dismutase (SOD) (P < .001) and catalase (CAT) (P < .001) activity
      of blood samples and decreased SOD (P < .001) and CAT (P < .05) activity observed
      in liver tissue curative groups compared with CCl4 curative group. In CCl4 group,
      liver tissue samples exhibited remarkable damage because of CCl4 and reduction of
      these damages were observed in the curative group. Our results showed that O.
      europaea leaf extract was effective in reducing hepatic damage caused by CCl4 by
      reducing lipid peroxidation, regulating antioxidant enzymes, and minimizing DNA
      damage.

PMID- 29648972
TI  - Randomized Controlled Trials in Adult Traumatic Brain Injury: A Systematic Review
      on the Use and Reporting of Clinical Outcome Assessments.
AB  - As part of efforts to improve study design, the use of outcome measures in
      randomized controlled trials (RCTs) in traumatic brain injury (TBI) is receiving
      increasing attention. This review aimed to assess how clinical outcome
      assessments (COAs) have been used and reported in RCTs in adult TBI. Systematic
      literature searches were conducted to identify medium to large (n >= 100) acute
      and post-acute TBI trials published since 2000. Data were extracted independently
      by two reviewers using a set of structured templates. Items from the Consolidated
      Standards of Reporting Trials (CONSORT) 2010 Statement and CONSORT patient
      reported outcomes (PROs) extension were used to evaluate reporting quality of
      COAs. Glasgow Outcome Scale/Extended (GOS/GOSE) data were extracted using a
      checklist developed specifically for the review. A total of 126 separate COAs
      were identified in 58 studies. The findings demonstrate heterogeneity in the use
      of TBI outcomes, limiting comparisons and meta-analyses of RCT findings. The
      GOS/GOSE was included in 39 studies, but implemented in a variety of ways, which
      may not be equivalent. Multi-dimensional outcomes were used in 30 studies, and
      these were relatively more common in rehabilitation settings. The use of PROs was
      limited, especially in acute study settings. Quality of reporting was variable,
      and key information concerning COAs was often omitted, making it difficult to
      know how precisely outcomes were assessed. Consistency across studies would be
      increased and future meta-analyses facilitated by (a) using common data elements
      (CDEs) recommendations for TBI outcomes and (b) following CONSORT guidelines when
      publishing RCTs.

PMID- 29648971
TI  - Anti-Inflammatory Effects of a Mixture of Lactic Acid Bacteria and Sodium
      Butyrate in Atopic Dermatitis Murine Model.
AB  - Atopic dermatitis is a chronic and recurrent inflammatory skin disease. Recently,
      probiotics have been shown to suppress allergic symptoms through immunomodulatory
      responses. In the present study, combinatorial effects on allergic symptoms were
      identified in BALB/c mice fed with a mixture of four species of probiotics,
      Bifidobacterium lactis, Lactobacillus casei, Lactobacillus rhamnosus, and
      Lactobacillus plantarum, and sodium butyrate. Following sensitization with whey
      protein, the mice were challenged and divided into two groups: (1) mice
      administered with phosphate-buffered saline as a control and (2) mice
      administered with the probiotic mixture and sodium butyrate. Allergic symptoms
      were assessed by measuring ear thicknesses, serum histamine and IL-10
      concentrations, and the quantities of leaked Evans blue. T cell differentiation
      was determined by analyzing the T cells groups in the mesenteric lymph nodes
      (MLNs) and spleen. To examine changes in the total gut microbiota, total fecal
      microflora was isolated, species identification was performed by DNA sequencing
      using Illumina MiSeq, and changes in intestinal beneficial bacteria were analyzed
      using quantitative polymerase chain reaction. Treatment with the probiotic
      mixture and sodium butyrate reduced ear thicknesses, the quantity of leaked Evans
      blue, and serum histamine values, while increasing serum IL-10 values. In the
      mouse model, the probiotic mixture and sodium butyrate increased Th1 and Treg
      cell differentiation in MLN and spleen tissues; the ratio of
      Firmicutes/Bacteroidetes, which is associated with reduction in allergic
      reactions; and microorganisms that lead to cell differentiation into Treg. These
      results suggest that the probiotic mixture and sodium butyrate can prevent and
      alleviate allergic symptoms.

PMID- 29648973
TI  - Male and Female Mice Exhibit Divergent Responses of the Cortical Vasculature to
      Traumatic Brain Injury.
AB  - We previously reported that traumatic brain injuries (TBI) alter the
      cerebrovasculature near the injury site in rats, followed by revascularization
      over a 2-week period. Here, we tested our hypothesis that male and female adult
      mice have differential cerebrovascular responses following a moderate controlled
      cortical impact (CCI). Using in vivo magnetic resonance imaging (MRI), a new
      technique called vessel painting, and immunohistochemistry, we found no
      differences between males and females in lesion volume, neurodegeneration, blood
      brain barrier (BBB) alteration, and microglia activation. However, females
      exhibited more astrocytic hypertrophy and heme-oxygenase-1 (HO-1) induction at 1
      day post-injury (dpi), whereas males presented with increased endothelial
      activation and expression of beta-catenin, shown to be involved in angiogenesis.
      At 7 dpi, we observed an increase in the number of vessels and an enhancement in
      vessel complexity in the injured cortex of males compared with females.
      Cerebrovasculature recovers differently after CCI, suggesting biological sex
      should be considered when designing new therapeutic agents.

PMID- 29648975
TI  - Short-Term Impact of Concussion in the NHL: An Analysis of Player Longevity,
      Performance, and Financial Loss.
AB  - Many studies have focused on the long-term impact of concussions in professional
      sports, but few have investigated short-term effects. This study examines
      concussion effects on individual players in the National Hockey League (NHL) by
      assessing career length, performance, and salary. Contracts, transactions, injury
      reports, and performance statistics from 2008-17 were obtained from the official
      NHL online publication. Players who sustained a concussion were compared with the
      2008-17 non-concussed player pool. Career length was analyzed using Kaplan-Meier
      survival curves and stratification of player age, experience, and longevity.
      Player performance and salary changes were evaluated between the years before
      versus after concussion. Performance and salary changes were compared against non
      concussed NHL athletes before/after their career midpoints. Of the 2194 eligible
      NHL players in the 9-year period, 309 sustained 399 concussions resulting in
      injury protocol. The probability of playing a full NHL season post-concussion was
      significantly decreased compared with the non-concussed pool (p < 0.05),
      specifically 65.0% versus 81.2% at 1 year into a player's career, 49.8% versus
      67.4% at 2 years, and 14.6% versus 43.7% at 5 years. Performance was reduced at
      all non-goalie positions post-concussion (p < 0.05). Players scored 2.5
      points/year less following a concussion. The total annualized financial impact
      from salary reductions after 1 concussion was $57.0 million, with a decrease of
      $292,000 per year in contract value per athlete. This retrospective study
      demonstrates that NHL concussions resulting in injury protocol activation lead to
      shorter career lengths, earnings reductions, and decreased performance when
      compared with non-concussed controls.

PMID- 29648974
TI  - Traumatic Brain Injury-Induced Acute Lung Injury: Evidence for Activation and
      Inhibition of a Neural-Respiratory-Inflammasome Axis.
AB  - Approximately 20-25% of traumatic brain injury (TBI) subjects develop acute lung
      injury (ALI), but the pathomechanisms of TBI-induced ALI remain poorly defined.
      Our previous work has shown that the inflammasome plays a critical role in TBI
      induced secondary pathophysiology and that inflammasome proteins are released in
      extracellular vesicles (EV) after TBI. Here we investigated whether EV-mediated
      inflammasome signaling contributed to the etiology of TBI-induced ALI. C57/BL6
      male mice were subjected to controlled cortical impact (CCI), and the brains and
      lungs were examined for inflammasome activation and ALI at 4 and 24 h after TBI.
      We show that TBI releases EV containing inflammasome proteins into serum that
      target the lung to cause ALI, supporting activation of a neural-respiratory
      inflammasome axis. Administration of a low-molecular-weight heparin (enoxaparin,
      a blocker of EV uptake) or treatment with a monoclonal antibody against apoptosis
      speck-like staining protein containing a caspase recruitment domain (anti-ASC)
      after adoptive transfer of EV isolated from TBI-injured mice significantly
      inhibited inflammasome activation in the lungs of recipient mice resulting in
      improved ALI scores.This axis constitutes an important arm of the innate
      inflammatory response in lung pathology after TBI and targeting this axis
      represents a novel therapeutic treatment for TBI-induced ALI.

PMID- 29648976
TI  - Adherence to Brain Trauma Foundation Guidelines for Management of Traumatic Brain
      Injury Patients and Its Effect on Outcomes: Systematic Review.
AB  - Traumatic brain injury (TBI) management based on Brain Trauma Foundation (BTF)
      guidelines is widely accepted and thought to improve outcome. The objectives of
      this study are to provide an overview of adherence to BTF guidelines and to
      explore which factors influence adherence. We conducted a search of relevant
      electronic bibliographic databases. Twenty articles met inclusion/exclusion
      criteria out of 666 articles screened. All were cohort studies. Wide variation in
      adherence to BTF guidelines was observed with a median of 66.2% (range 0-100%).
      The lowest median adherence was observed with surgical management (14%), whereas
      the highest was observed with oxygenation (100%), steroid (97.8%), and blood
      pressure recommendation (92.3%). Variability was primarily explained by the
      variation in the strength of evidence of each recommendation. Treating patients
      with higher severity of injury as well as treatment in a Level I trauma center
      positively influenced adherence. Overall, adherence to BTF guidelines varies.
      Further research is required to strengthen the current evidence and to identify
      factors related to adherence to guidelines from a professional prospective.

PMID- 29648977
TI  - Severe Traumatic Brain Injury Patients without Focal Lesion but with Behavioral
      Disorders: Shrinkage of Gray Matter Nuclei and Thalamus Revealed in a Pilot Voxel
      Based MRI Study.
AB  - After a traumatic brain injury (TBI), behavioral disorders can occur without
      major focal brain lesion, and in these situations, their pathophysiology remains
      unclear. The aim of this study is to examine whether TBI patients with behavioral
      disorders but without any focal damage, as observed from an initial clinical CT
      scan, present subtle volumetric alterations that could be measured voxel-by-voxel
      in the whole brain with MRI. Eight male adults with severe TBI who had behavioral
      sequela but not major focal cerebral lesion and 17 age-matched controls underwent
      a volumetric T1-weighted 1.5T MRI. A two step analysis was performed. First, gray
      matter (GM) and white matter (WM) volumes were compared between groups using
      voxel-based morphometry. Second, we examined brain regions systematically damaged
      using the sum of the individual binary maps obtained from z-maps thresholded at 
      1.75 for significant GM and WM atrophy. TBI patients had lower GM volume than
      controls (p < 0.001, uncorrected) in the right parahippocampal gyrus; left and
      right superior, middle, and inferior temporal gyri; left superior frontal gyrus;
      right middle frontal gyrus; thalami; mammillary bodies; caudate nuclei; insulae;
      cerebellar cortex; and vermis. WM volume was lower (p < 0.001, uncorrected) in
      the TBI group than in controls in the periventricular area and around the basal
      nuclei. We found shrinkage in the dorsomedial thalami in each of the TBI
      patients, and in the posterior part of the right putamen and caudate nuclei in
      seven TBI patients. Shrinkage in the dorsomedial thalami and in the posterior
      part of the right putamen and caudate nuclei may be a common effect of the
      disseminated microscopic lesions, and be associated with behavioral issues in
      severe TBI patients without major focal lesions.

PMID- 29648978
TI  - FGF21 Protects the Blood-Brain Barrier by Upregulating PPARgamma via FGFR1/beta
      klotho after Traumatic Brain Injury.
AB  - Blood-brain barrier (BBB) disruption and dysfunction result in brain edema, which
      is responsible for more than half of all deaths after severe traumatic brain
      injury (TBI). Fibroblast growth factor 21 (FGF21) has a potential neuroprotective
      function in the brain. However, the effects and underlying possible mechanism of
      action on BBB integrity following TBI remain unknown. The purpose of the current
      study was to determine the effects of FGF21 on BBB protection and TBI treatment.
      The effects of recombinant human FGF21 (rhFGF21) on BBB integrity and on tight
      junction (TJ) and adhesion junction (AJ) proteins were investigated both in a TBI
      mouse model and an in vitro BBB disruption model established with tumor necrosis
      factor alpha (TNF-alpha)-induced human brain microvascular endothelial cells
      (HBMECs). The ability of rhFGF21 to form an FGF21/FGFR1/beta-klotho complex was
      confirmed by in vitro beta-klotho small interfering RNA (siRNA) transfection and
      FGFR1 co-immunoprecipitation. In addition, the specific FGFR1 and peroxisome
      proliferator-activated receptor gamma (PPARgamma) inhibitors PD173074 and GW9662,
      respectively, were applied to further explore the possible mechanism of rhFGF21
      in BBB maintenance after TBI. rhFGF21 markedly reduced neurofunctional behavior
      deficits and cerebral edema degree, preserved BBB integrity, and recued brain
      tissue loss and neuron apoptosis in the mouse model after TBI. Both in vivo and
      in vitro, rhFGF21 upregulated TJ and AJ proteins, thereby preserving the BBB.
      Moreover, rhFGF21 activated PPARgamma in TNF-alpha-induced HBMECs through
      formation of an FGF21/FGFR1/beta-klotho complex. rhFGF21 protected the BBB
      through FGF21/FGFR1/beta-klotho complex formation and PPARgamma activation, which
      upregulated TJ and AJ proteins.

PMID- 29648980
TI  - Cerebrospinal Fluid Endothelin-1 in Severe Traumatic Brain Injury.

PMID- 29648979
TI  - Long-Term Functional and Structural Consequences of Primary Blast Overpressure to
      the Eye.
AB  - Acoustic blast overpressure (ABO) injury in military personnel and civilians is
      often accompanied by delayed visual deficits. However, most animal model studies
      dealing with blast-induced visual defects have focused on short-term (<=1 month)
      changes. Here, we evaluated long-term (<=8 months) retinal structure and function
      deficits in rats with ABO injury. Adult male Long-Evans rats were subjected to
      ABO from a single blast (approximately 190 dB SPL, ~63 kPa, @80 psi), generated
      by a shock tube device. Retinal function (electroretinography; ERG), visual
      function (optomotor response), retinal thickness (spectral domain-optical
      coherence tomography; SD-OCT), and spatial cognition/exploratory motor behavior
      (Y-maze) were measured at 2, 4, 6, and 8 months post-blast. Immunohistochemical
      analysis of glial fibrillary acidic protein (GFAP) in retinal sections was
      performed at 8 months post-blast. Electroretinogram a- and b-waves, oscillatory
      potentials, and flicker responses showed greater amplitudes with delayed implicit
      times in both eyes of blast-exposed animals, relative to controls. Contrast
      sensitivity (CS) was reduced in both eyes of blast-exposed animals, whereas
      spatial frequency (SF) was decreased only in ipsilateral eyes, relative to
      controls. Total retinal thickness was greater in both eyes of blast-exposed
      animals, relative to controls, due to increased thickness of several retinal
      layers. Age, but not blast exposure, altered Y-maze outcomes. GFAP was greatly
      increased in blast-exposed retinas. ABO exposure resulted in visual and retinal
      changes that persisted up to 8 months post-blast, mimicking some of the visual
      deficits observed in human blast-exposed patients, thereby making this a useful
      model to study mechanisms of injury and potential treatments.

PMID- 29648981
TI  - Glibenclamide Produces Region-Dependent Effects on Cerebral Edema in a Combined
      Injury Model of Traumatic Brain Injury and Hemorrhagic Shock in Mice.
AB  - Cerebral edema is critical to morbidity/mortality in traumatic brain injury (TBI)
      and is worsened by hypotension. Glibenclamide may reduce cerebral edema by
      inhibiting sulfonylurea receptor-1 (Sur1); its effect on diffuse cerebral edema
      exacerbated by hypotension/resuscitation is unknown. We aimed to determine if
      glibenclamide improves pericontusional and/or diffuse edema in controlled
      cortical impact (CCI) (5m/sec, 1 mm depth) plus hemorrhagic shock (HS) (35 min),
      and compare its effects in CCI alone. C57BL/6 mice were divided into five groups
      (n = 10/group): naive, CCI+vehicle, CCI+glibenclamide, CCI+HS+vehicle, and
      CCI+HS+glibenclamide. Intravenous glibenclamide (10 min post-injury) was followed
      by a subcutaneous infusion for 24 h. Brain edema in injured and contralateral
      hemispheres was subsequently quantified (wet-dry weight). This protocol brain
      water (BW) = 80.4% vehicle vs. 78.3% naive, p < 0.01) but was not reduced by
      glibenclamide (I%BW = 80.4%). Ipsilateral edema also developed in CCI alone (I%BW
      = 80.2% vehicle vs. 78.3% naive, p < 0.01); again unaffected by glibenclamide
      (I%BW = 80.5%). Contralateral (C) %BW in CCI+HS was increased in vehicle (78.6%)
      versus naive (78.3%, p = 0.02) but unchanged in CCI (78.3%). At 24 h,
      glibenclamide treatment in CCI+HS eliminated contralateral cerebral edema (C%BW =
      78.3%) with no difference versus naive. By 72 h, contralateral cerebral edema had
      resolved (C%BW = 78.5 +/- 0.09% vehicle vs. 78.3 +/- 0.05% naive). Glibenclamide
      decreased 24 h contralateral cerebral edema in CCI+HS. This beneficial effect
      merits additional exploration in the important setting of TBI with polytrauma,
      shock, and resuscitation. Contralateral edema did not develop in CCI alone.
      Surprisingly, 24 h of glibenclamide treatment failed to decrease ipsilateral
      edema in either model. Interspecies dosing differences versus prior studies may
      play an important role in these findings. Mechanisms underlying brain edema may
      differ regionally, with pericontusional/osmolar swelling refractory to
      glibenclamide but diffuse edema (via Sur1) from combined injury and/or
      resuscitation responsive to this therapy. TBI phenotype may mandate precision
      medicine approaches to treat brain edema.

PMID- 29648983
TI  - Enhancement of Brain d-Serine Mediates Recovery of Cognitive Function after
      Traumatic Brain Injury.
AB  - Cognitive deficits, especially memory loss, are common and devastating
      neuropsychiatric sequelae of traumatic brain injury (TBI). The deficits may
      persist for years and may be accompanied by increased risk of developing early-
      onset dementia. Past attempts to reverse the neuropathological effects of brain
      injury with glutamate-N-methyl-d-aspartate (NMDA) antagonists failed to show any
      benefits or worsened the outcome, suggesting that activation, rather than
      blockage, of the NMDA receptor (NMDAR) may be useful in the subacute period after
      TBI and stroke. Activation of the NMDAR requires occupation of the glycine
      modulatory site by co-agonists to achieve its synaptic functions. Glycine and d
      serine are endogenous ligands/co-agonists of synaptic NMDARs in many areas of the
      mature brain. The aim of the present study was to evaluate the effect of 6
      chlorobenzo(d)isoxazol-3-ol (CBIO), an inhibitor of D-amino acid oxidase (DAAO),
      which degrades d-serine, on cognitive outcome in a mouse model of TBI. Because
      treating TBI animals with CBIO elevates the endogenous levels of d-serine, we
      compared this novel treatment with treatment by exogenous d-serine alone and
      combined with CBIO. The results show that a single treatment (24 h post-injury)
      with CBIO in the mouse model of closed head injury significantly improves
      cognitive and motor function, and decreases lesion volume and the inflammatory
      response. Moreover, the compound proved to be neuroprotective, as the hippocampal
      volume and the number of neurons in hippocampal regions increased. Treatment with
      CBIO boosted the NR1 and phospho- NR1 subunits of the NMDAR and affected the
      CREB, phospho-CREB, and brain-derived neurotropic factor (BDNF) pathways. These
      findings render CBIO a promising, novel treatment for cognitive impairment
      following TBI.

PMID- 29648982
TI  - Effects of Mitochondrial Transplantation on Bioenergetics, Cellular
      Incorporation, and Functional Recovery after Spinal Cord Injury.
AB  - Our previous studies reported that pharmacological maintenance of mitochondrial
      bioenergetics after experimental spinal cord injury (SCI) provided functional
      neuroprotection. Recent evidence indicates that endogenous mitochondrial transfer
      is neuroprotective as well, and, therefore, we extended these studies with a
      novel approach to transplanting exogenous mitochondria into the injured rat
      spinal cord. Using a rat model of L1/L2 contusion SCI, we herein report that
      transplantation of exogenous mitochondria derived from either cell culture or
      syngeneic leg muscle maintained acute bioenergetics of the injured spinal cord in
      a concentration-dependent manner. Moreover, transplanting transgenically labeled
      turbo green fluorescent (tGFP) PC12-derived mitochondria allowed for
      visualization of their incorporation in both a time-dependent and cell-specific
      manner at 24 h, 48 h, and 7 days post-injection. tGFP mitochondria co-localized
      with multiple resident cell types, although they were absent in neurons. Despite
      their contribution to the maintenance of normal bioenergetics, mitochondrial
      transplantation did not yield long-term functional neuroprotection as assessed by
      overall tissue sparing or recovery of motor and sensory functions. These
      experiments are the first to investigate mitochondrial transplantation as a
      therapeutic approach to treating spinal cord injury. Our initial bioenergetic
      results are encouraging, and although they did not translate into improved long
      term outcome measures, caveats and technical hurdles are discussed that can be
      addressed in future studies to potentially increase long-term efficacy of
      transplantation strategies.

PMID- 29648984
TI  - Facilitation of Locomotor Spinal Networks Activity by Buspirone after a Complete
      Spinal Cord Lesion in Mice.
AB  - Despite efforts to potentiate spinal cord lesioned (SCL) patients' functional
      recovery with multi-targeted therapy combining pharmacological treatment and
      training, consistent improvements in locomotor control by descending transmission
      or spinal network facilitation are still eluding clinicians and researchers.
      Lately, United States Food and Drug Administration-approved buspirone has shown
      promise and promoted locomotor-like movement occurrence in SCL patients, but
      evidence on how and where it exerts its effects is lacking. The objective of the
      present study was, first, to verify buspirone effect on locomotor spinal network
      and to evaluate if it promoted functional recovery when combined with training.
      Also, we evaluated buspirone impact on locomotion in mice that had recovered from
      a previous hemisection before sustaining the spinal transection. This dual lesion
      paradigm has allowed confirmation of spinal network involvement in recovery after
      an incomplete SCL. Buspirone acutely increased the number of steps taken, the
      coupling strength between hindlimbs, angular excursion of the hip joint during
      locomotion, and improved paw positioning at contact and paw drag (ps < 0.05).
      Moreover, it induced long-lasting improvements of paw positioning at contact and
      paw drag when combined with training in mice after a dual lesion paradigm.
      Altogether, the results indicate that buspirone exerts considerable acute
      facilitation of spinally mediated locomotion, and could be used in combination
      with training to promote functional recovery after SCL.

PMID- 29648985
TI  - Feasibility of Telemetric Intracranial Pressure Monitoring in the Neuro Intensive
      Care Unit.
AB  - Intracranial pressure (ICP) monitoring is crucial in the management of acute
      neurosurgical conditions such as traumatic brain injury (TBI). However,
      pathological ICP may persist beyond the admission to the neuro intensive care
      unit (NICU). We investigated the feasibility of telemetric ICP monitoring in the
      NICU, as this technology provides the possibility of long-term ICP assessment
      beyond NICU discharge. In this prospective investigation, we implanted telemetric
      ICP sensors (Raumedic Neurovent-P-tel) instead of conventional, cabled ICP
      sensors in patients undergoing decompressive craniectomy. We recorded ICP curves,
      duration of ICP monitoring, signal quality, and complications. Seventeen patients
      were included (median age 55 years) and diagnoses were: severe TBI (8), malignant
      middle cerebral artery infarction (8), and spontaneous intracerebral hemorrhage
      (1). In total, 3015 h of ICP monitoring were performed, and the median duration
      of ICP monitoring was 188 h (interquartile range [IQR] 54-259). The ICP signal
      was lost 613 times (displacement of the reader unit on the skin) for a median of
      1.5 min, corresponding to 0.8% of the total monitoring period. When the signal
      was lost, it could always be restored by realignment of the reader unit on the
      skin above the telemetric sensor. Sixteen of 17 patients survived the NICU
      admission, and ICP gradually decreased from 10.7 mm Hg (IQR 7.5-13.6) during the
      first postoperative day to 6.3 mm Hg (IQR 4.0-8.3) after 1 week in the NICU. All
      17 implanted telemetric sensors functioned throughout the NICU admission, and no
      wound infections were observed. Therefore, telemetric ICP monitoring in an acute
      neurosurgical setting is feasible. Signal quality and stability are sufficient
      for clinical decision making based on mean ICP. The low sampling frequency (5 Hz)
      does not permit analysis of intracranial pulse wave morphology, but resolution is
      sufficient for calculation of derived indices such as the pressure reactivity
      index (PRx).

PMID- 29648986
TI  - A Single Primary Blast-Induced Traumatic Brain Injury in a Rodent Model Causes
      Cell-Type Dependent Increase in Nicotinamide Adenine Dinucleotide Phosphate
      Oxidase Isoforms in Vulnerable Brain Regions.
AB  - Blast-induced traumatic brain injury (bTBI) is a leading cause of morbidity in
      soldiers on the battlefield and in training sites with long-term neurological and
      psychological pathologies. Previous studies from our laboratory demonstrated
      activation of oxidative stress pathways after blast injury, but their
      distribution among different brain regions and their impact on the pathogenesis
      of bTBI have not been explored. The present study examined the protein expression
      of two isoforms: nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 1
      and 2 (NOX1, NOX2), corresponding superoxide production, a downstream event of
      NOX activation, and the extent of lipid peroxidation adducts of 4-hydroxynonenal
      (4HNE) to a range of proteins. Brain injury was evaluated 4 h after the shock
      wave exposure, and immunofluorescence signal quantification was performed in
      different brain regions. Expression of NOX isoforms displayed a differential
      increase in various brain regions: in hippocampus and thalamus, there was the
      highest increase of NOX1, whereas in the frontal cortex, there was the highest
      increase of NOX2 expression. Cell-specific analysis of changes in NOX expression
      with respect to corresponding controls revealed that blast resulted in a higher
      increase of NOX1 and NOX 2 levels in neurons compared with astrocytes and
      microglia. Blast exposure also resulted in increased superoxide levels in
      different brain regions, and such changes were reflected in 4HNE protein adduct
      formation. Collectively, this study demonstrates that primary blast TBI induces
      upregulation of NADPH oxidase isoforms in different regions of the brain
      parenchyma and that neurons appear to be at higher risk for oxidative damage
      compared with other neural cells.

PMID- 29648988
TI  - Coccidiostats in milk: development of a multi-residue method and transfer of
      salinomycin and lasalocid from contaminated feed.
AB  - A confirmatory multi-residue method was developed for the determination in milk
      of 19 coccidiostats (amprolium, arprinocid, clazuril, clopidol, decoquinate,
      diclazuril, ethopabate, halofuginone, lasalocid, maduramicin, monensin, narasin,
      nicarbazin, nequinate, robenidine, salinomycin, semduramicin, toltrazuril sulfone
      and toltrazuril sulfoxide). Sample preparation utilising extraction with organic
      solvent and clean up by SPE and freezing was found reliable and time-efficient.
      Optimised chromatography and MS conditions with positive and negative ESI
      achieved sufficient sensitivity and selectivity. Validation experiments has
      proven method usefulness for routine analysis of coccidiostats in milk samples.
      An on-farm study conducted on dairy cows fed with experimentally contaminated
      feed with salinomycin and lasalocid showed negligible transfer to milk. No
      residues of lasalocid were found in collected samples. Salinomycin was found only
      in 5 of 168 samples analysed, while the concentrations of salinomycin in those
      samples (0.119-0.179 ug kg-1) was significantly below the limit of salinomycin in
      milk set by European Union legislation. Such low concentrations of both
      coccidiostats cannot be explained by conjugation during dairy cows' metabolism,
      as shown by experiments with enzymatic hydrolysis.

PMID- 29648987
TI  - Variability of Leg Kinematics during Overground Walking in Persons with Chronic
      Incomplete Spinal Cord Injury.
AB  - Incomplete spinal cord injury (iSCI) often leads to partial disruption of spinal
      pathways that are important for motor control of walking. Persons with iSCI
      present with deficits in walking ability in part because of inconsistent leg
      kinematics during stepping. Although kinematic variability is important for
      normal walking, growing evidence indicates that excessive variability may limit
      walking ability and increase reliance on assistive devices (AD) after iSCI. The
      purpose of this study was to assess the effects of iSCI-induced impairments on
      kinematic variability during overground walking. We hypothesized that iSCI
      results in greater variability of foot and joint displacement during overground
      walking compared with controls. We further hypothesized that variability is
      larger in persons with limited walking speed and greater reliance on ADs. To test
      these hypotheses, iSCI and control subjects walked overground. Kinematic
      variability was quantified as step-to-step foot placement variability (end
      point), and variability in hip-knee, hip-ankle, and knee-ankle joint space
      (angular coefficient of correspondence [ACC]). We characterized sensitivity of
      kinematic variability to cadence, auditory cue, and AD. Supporting our
      hypothesis, persons with iSCI exhibited greater kinematic variability than
      controls, which scaled with deficits in overground walking speed (p < 0.01).
      Significant correlation between ACC and end-point variability, and with walking
      speed, indicates that both are markers of walking performance. Moreover, hip-knee
      and hip-ankle ACC discriminated AD use, indicating that ACC may capture AD
      specific control strategies. We conclude that increased variability of foot and
      joint displacement are indicative of motor impairment severity and may serve as
      therapeutic targets to restore walking after iSCI.

PMID- 29648989
TI  - Analysis of sexual problems in men with psoriasis.
AB  - INTRODUCTION: Psoriasis may have negative impact on many aspects of patient life.
      OBJECTIVE: The aim of the study was to evaluate the influence of psoriasis on
      erectile dysfunction and other sexual problems in men with psoriasis. MATERIALS
      AND METHODS: A total of 76 men aged between 20 and 66 years (mean 43.9+/-13.2
      years) were enrolled. Psoriasis severity assessed according to PASI ranged from
      2.0 to 49.8 points (mean 15.1+/-10.3 points). All patients were asked to complete
      International Index of Erectile Function (IIEF-5), Beck's Depression Inventory
      and Dermatology Life Quality Index. A detailed medical history regarding sexual
      problems was also collected. RESULTS: Erectile dysfunction was found in 43.8% of
      patients. The severity of erectile dysfunction negatively correlated with the age
      of patients (rho = -0.42; p<0.01) and depressive symptoms assessed by BDI (rho = 
      0.39, p<0.01). Majority of patients (77.6%) declared, that the skin condition at
      least occasionally negatively influenced their sexual life. Patients with more
      severe psoriasis more often avoided sexual intercourses (p<0.01) and felt ashamed
      in front of their sexual partners (p = 0.04). The vast majority of men (96.1%)
      felt unattractive during psoriasis exacerbation and felt embarrassed, if skin
      lesions were present on uncovered body regions. More than a half avoided social
      activities and sexual intercourses due to psoriasis. Moreover, 44.7% experienced
      rejection during their life because of psoriasis. CONCLUSIONS: Psoriasis
      negatively influences mostly emotional aspects of sexual life. Psychological
      disturbances, severity of the disease, smoking, metabolic syndrome and other
      concomitant diseases might influence on presence and progression of erectile
      dysfunction in psoriatic patients. Dermatologists should be aware about these
      problems to put more attention on this aspect of psoriasis.

PMID- 29648990
TI  - The peripheral cannulas in extracorporeal life support.
AB  - Femoral cannulation is a minimally invasive method which is an alternative method
      for central cannulation. This review focuses on the parameters and features of
      the available peripheral cannulas. Nowadays there exist many peripheral cannulas
      in a variety of sizes, configurations and lengths to meet the specific needs of
      the patients. Modern cannulas are strong, thin-walled and one piece reinforced
      constructions. Furthermore, modern cannulas are manufactured from a biocompatible
      material and surface coatings are applied to the cannulas to reduce the
      activation of the clotting. When peripheral cannulas are applied, bleeding,
      thrombosis and hemolysis are the most common complications.

PMID- 29648991
TI  - Three-dimensional bioglass-collagen-phosphatidylserine scaffolds designed with
      functionally graded structure and mechanical features.
AB  - The development of scaffolds featuring spatiotemporal controlled release of drugs
      is highly desirable. The goal of this study is to construct an inhomogeneous
      scaffold with gradient pore structure from top layer to bottom layer. The
      scaffolds were prepared using bioglass (BG), phosphatidylserine (PS) and
      steroidal saponins (SS) loaded collagen (COL) microparticles as the main
      components. The resulting scaffold constructs were characterized in terms of
      their morphology, drug release kinetics and mechanisms, as well as macroscopic
      form stability and mechanical properties. Pore interconnectivity and graded
      distribution were demonstrated using scanning electron microscopy (SEM). Such
      constructs have been further shown to be advantageous for temporal and spatial
      control of drug release and deposition in the scaffolds, with a potential to
      repair bone defect more precisely and effectively. Changes in the BG content
      resulted in distinct macroscopic form stability and mechanical properties to
      scaffolds. An increase in the BG content in scaffolds led to less volume swell as
      well as higher ultimate strength and compressive modulus, which makes the
      scaffolds mechanically adjustable according to certain structures and properties
      of different bone defect sites. The developed scaffolds may show promise for
      promoting bone tissue regeneration.

PMID- 29648992
TI  - International normalized ratio (INR) testing in Europe: between-laboratory
      comparability of test results obtained by Quick and Owren reagents.

PMID- 29648993
TI  - Serum carbohydrate sulfotransferase 7 in lung cancer and non-malignant pulmonary
      inflammations.
AB  - BACKGROUND: Carbohydrate sulfotransferases (CHST) were shown to be involved in
      carcinogenesis. The aim of the study was to assess the diagnostic value of serum
      CHST7 concentration in differentiation between lung cancer and non-malignant
      pulmonary inflammations. METHODS: Clinical case-control study involving 125
      participants was conducted: the control group containing cases of pneumonia and
      chronic obstructive pulmonary disease was compared to the lung cancer group
      composed of primary and metastatic cancers. Serum concentrations of CHST7 and
      routinely used markers including carcinoembryonic antigen (CEA), cytokeratin
      fragment 21-1 (CYFRA 21-1) and neuron-specific enolase (NSE) were determined for
      each participant using immunochemical methods. Statistical association, receiver
      operating characteristic (ROC) analysis and cross-validation were used for the
      evaluation of CHST7 either as a standalone biomarker or as a part of a biomarker
      panel. RESULTS: In comparison to the control group, serum CHST7 was elevated in
      lung cancer (p<0.001), but no differences between the overall stages of primary
      cancers were detected (p=0.828). The differentiation performance in terms of ROC
      area under curve (AUC) was 0.848 making CHST7 superior biomarker to the NSE
      (p=0.031). In comparison to CEA and CYFRA 21-1, the performance differences were
      not detected. CHST7 was not correlated to other biomarkers, and its addition to
      the routine biomarker panel significantly improved the cross-validated accuracy
      (85.6% vs. 75.2%) and ROC AUC (p=0.004) of the differentiation using a machine
      learning approach. CONCLUSIONS: Serum CHST7 is a promising biomarker for the
      differentiation between lung cancer and non-malignant pulmonary inflammations.

PMID- 29648994
TI  - Within-subject biological variation of activated partial thromboplastin time,
      prothrombin time, fibrinogen, factor VIII and von Willebrand factor in pregnant
      women.
AB  - BACKGROUND: During pregnancy, interpretation of results from coagulation
      parameters can be difficult as the physiological changes that occur may affect
      the biochemical parameters. The aim of this study was to describe the normal
      course of five coagulation parameters in healthy pregnancies, and to estimate the
      within-subject biological variation (CVI). METHODS: Blood samples were obtained
      every 4th week during pregnancy and three samples after delivery in 20 healthy
      women and every 4th week during a 40-week period in 19 healthy non-pregnant
      women. Activated partial thromboplastin time (APTT), prothrombin time (PT), PT
      International Normalized Ratio (INR), fibrinogen, factor VIII clot (FVIII:C) and
      von Willebrand factor antigen (vWF:Ag) were analyzed. The physiological changes
      during pregnancy were compensated by transformation into multiples of the median
      (MoM) and it is natural logarithm (lnMoM) in order to establish a kind of steady
      state, and CVI was calculated from the standard deviation. RESULTS: During
      pregnancy, APTT, PT and INR remained unchanged or decreased, depending upon the
      reagent used, while fibrinogen, FVIII:C and vWF:Ag increased gradually until
      delivery. The CVI in pregnancy were 2.2 and 3.0% for APTT, 2.3 and 2.6% for PT,
      2.2 and 2.3% for INR, 7.2% for fibrinogen, 12.2% for FVIII:C and 11.3% for
      vWF:Ag, and corresponded with the CVI in non-pregnant women. CONCLUSIONS:
      Transformation of coagulation parameters in healthy pregnancies to MoM is a tool
      to establish a kind of steady state. Although there is a physiological change in
      these coagulation parameters during pregnancy, the CVI after lnMoM transformation
      was comparable with the CVI of non-pregnant women.

PMID- 29648995
TI  - Cerebrospinal fluid free light chains as diagnostic biomarker in
      neuroborreliosis.
AB  - BACKGROUND: Free light chains (FLC) have been proposed as diagnostic biomarker in
      patients with inflammatory central nervous system diseases. The objective of this
      study was to investigate the diagnostic utility of intrathecal kappa- and lambda
      FLC synthesis in patients with neuroborreliosis. METHODS: kappa- and lambda-FLC
      were measured by nephelometry under blinded conditions in cerebrospinal fluid
      (CSF) and serum sample pairs of 34 patients with neuroborreliosis and compared to
      a cohort of 420 control patients. kappa-FLC index was calculated as [CSF kappa
      FLC/serum kappa-FLC]/[CSF albumin/serum albumin], and lambda-FLC index in
      analogy. RESULTS: kappa-FLC and lambda-FLC index were significantly elevated in
      patients with neuroborreliosis compared to the control group. At a specificity
      level of 95%, kappa-FLC and lambda-FLC index showed a diagnostic sensitivity of
      88.2% and 100%. In comparison, IgM and IgG synthesis according to Reiber formula,
      IgG index >0.7 and OCB status reached a sensitivity of 83.9%, 44.1%, 58.8% and
      64.7%. CONCLUSION: These findings support the diagnostic value of intrathecal FLC
      synthesis in neuroborreliosis patients and demonstrate a valid, easy and rater
      independent alternative for the detection of an intrathecal immunoglobulin
      production.

PMID- 29648996
TI  - Serum procalcitonin concentration within 2 days postoperatively accurately
      predicts outcome after liver resection.
AB  - BACKGROUND: Relatively high mortality and morbidity rates are reported after
      liver resection (LR). However, the early predictors of complications after LR are
      not clear. This study was performed to clarify the usefulness of procalcitonin
      (PCT) for the early prediction of complications after elective LR. METHODS: This
      observational study included 72 consecutive patients who underwent elective LR
      from December 2015 to March 2017. Patients were categorized into two groups:
      those with and without postoperative complications (Clavien-Dindo grade >=II).
      The values of postoperative inflammatory markers (white blood cell [WBC] count, C
      reactive protein [CRP] and PCT) were compared between the two groups. RESULTS:
      CRP and PCT were significantly higher in patients with than without
      complications; however, the WBC count showed no difference within 5 days
      postoperatively. The maximum area under the receiver operating characteristic
      curves within 2 days after LR using the WBC count, CRP and PCT were 0.608, 0.697
      and 0.860, respectively, PCT had the best predictive ability in the early
      postoperative period. The PCT level peaked within 2 days postoperatively in 61
      patients (85%). The maximum PCT level within 2 days postoperatively (PCT1-2) was
      significantly higher in patients with than without complications (0.52 vs. 0.19
      ng/mL, p<0.001). A cutoff PCT1-2 level of 0.35 ng/mL achieved 80% sensitivity and
      83% specificity. In patients without complications, there was no difference in
      PCT1-2 even when the surgical procedure differed (p=0.935). CONCLUSIONS: PCT1-2
      is an early predictive marker after LR and can be similarly used regardless of
      the LR procedure.

PMID- 29648997
TI  - Interactive effects of alcohol and chloroquine on hematologic profile of Wistar
      rats.

PMID- 29648998
TI  - Orphan drugs: trends and issues in drug development.

PMID- 29648999
TI  - Cord blood klotho levels are inversely associated with leptin in healthy Latino
      neonates at risk for obesity.
AB  - BACKGROUND: Klotho serum levels reflect nutritional state in adults including
      obesity and anorexia. The relationship between cord blood klotho levels at birth
      and parameters of growth including anthropometrics are not known. METHODS: We
      evaluated the relationship between cord blood klotho, leptin and adipocyte
      hormones and infant, child and maternal anthropometrics and maternal depression
      in a cohort of 73 children. Non-parametric tests were used to assess differences
      between dichotomous and categorical predictors and klotho levels and Spearman's
      rank coefficients were used to assess the relationship between klotho levels and
      continuous predictors. A multivariable log transformed linear regression model
      was used to test for independent predictors of serum klotho levels. RESULTS: Mean
      klotho levels were 2864.9+/-1409.7 (pg/mL) in cord blood and we found no
      relationship with infant sex, delivery specifics including gestational age or
      anthropometrics at birth. There was similarly no association between klotho
      levels at birth and future obesity at age 2. Leptin levels at birth were
      inversely associated with klotho levels in multivariable models after adjusting
      for other covariates (p<0.01). Similarly, in multivariable models insulin levels
      were inversely correlated with klotho levels (p=0.03). Leptin levels in our
      cohort of at-risk infants were more than 50% higher than other studies with
      neonates. CONCLUSIONS: We found no associations between weight or length at birth
      or obesity in early childhood and cord blood klotho levels. Cord blood klotho
      levels were inversely correlated with leptin and insulin levels at birth and
      should be further investigated to better understand the inter-relationship
      between this hormone and key regulators of growth and adiposity.

PMID- 29649000
TI  - Review and evaluation of patient-centered psychosocial assessments for children
      with central precocious puberty or early puberty.
AB  - The objective of this study was to assess the current use of patient-centered
      psychosocial assessments for the evaluation of children with central precocious
      puberty (CPP). Studies evaluating the psychosocial impact of CPP were identified
      through searches of the PubMed and Cochrane Library databases,
      ClinicalTrials.gov, a drug prescribing information database, and regulatory
      websites. Studies were screened using prespecified inclusion and exclusion
      criteria. Potentially relevant patient-centered outcome assessments (including
      patient-, parent- or observer-reported measures) used in the identified studies
      were evaluated in detail for their relevance in CPP. Of the 467 studies
      identified, 15 met the inclusion criteria. Frequently assessed concepts included
      depression and anxiety, behavior and behavioral problems, body image and self
      esteem and personality type/characteristics. Among the assessments used in the
      identified studies, the Child Behavior Checklist, Pediatric Quality of Life
      Inventory (PedsQL), SF-10 for Children and Child Health Questionnaire were
      comprehensively evaluated. The PedsQL showed promise as a patient-centered
      outcome measure in CPP. Although there is a lack of validated tools measuring
      psychosocial health and health-related quality of life in patients with CPP, the
      PedsQL captures issues seen in this patient population and is relatively easy to
      administer. Further studies using this and other tools in children with CPP are
      needed.

PMID- 29649001
TI  - Trends in characteristics of women choosing contraindicated home births.
AB  - OBJECTIVE: To characterize the American College of Obstetricians and
      Gynecologists (ACOG) contraindicated home births and the women who are receiving
      these births in hopes of identifying venues for intervention. METHODS: The
      National Center for Health Statistics (NCHS) birth certificate records from 1990
      to 2015 were used. "Planned home births" were defined as those births in which
      birthplace was coded as "residence" and birth attendant was coded as "certified
      nurse midwife (CNM)" or "other midwife". Contraindicated home births were defined
      as "planned home births" from 1990 to 2015 that had one or more of the ACOG risk
      factors for home births, which include vaginal birth after prior cesarean
      delivery (VBAC), breech presentation and multiple gestations. RESULTS: A review
      of trends in contraindicated home births from 1990 to 2015 suggests that they are
      increasing in number (481-1396) and as a percentage of total births (0.01%-0.04%,
      P<0.001). There has been an increase in the proportion of college-educated women
      (31%-51%, P<0.001). Most women receive prenatal care (>95%), which is most
      frequently initiated in the first trimester. The majority of home births were
      paid out-of-pocket (65%-69%). CONCLUSION: The increasing number of
      contraindicated home births in the United States requires public health action.
      Home births are likely a matter of choice rather than a lack of resources. It is
      unclear if women choose home births while knowing the risk or due to a lack of
      information. Prenatal education about contraindicated home births is possible, as
      almost all women receive prenatal care.

PMID- 29649004
TI  - Atypical Hepatocellular Neoplasms: Review of Clinical, Morphologic,
      Immunohistochemical, Molecular, and Cytogenetic Features.
AB  - The distinction of hepatocellular adenoma from well-differentiated hepatocellular
      carcinoma (HCC) can be difficult in some cases, especially on biopsy specimens.
      These borderline cases often occur in men or older patients and may have beta
      catenin activation or focal atypical morphologic features (such as small cell
      change, prominent pseudoacinar formation, cytologic atypia, focally thick plates,
      and/or focal reticulin loss) that are insufficient for an unequivocal diagnosis
      of HCC. The term "atypical hepatocellular neoplasm" has been advocated for these
      tumors, but a number of other terms, including "atypical adenoma,"
      "hepatocellular neoplasm of uncertain malignant potential," and "well
      differentiated hepatocellular neoplasm with atypical or borderline features" have
      also been proposed. This review proposes guidelines for designating tumors as
      atypical hepatocellular neoplasm and describes clinical, morphologic,
      immunohistochemical, molecular, and cytogenetic features that distinguish these
      tumors from typical hepatocellular adenoma and HCC.

PMID- 29649005
TI  - Cutaneous Smooth Muscle Tumors: A Review.
AB  - Smooth muscle tumors occur infrequently in the skin. They consist of a diverse
      group of lesions representing hamartomas as well as benign and malignant
      neoplasms. They may arise from arrector pili muscle, specialized smooth muscle of
      the genitalia, or vascular smooth muscle. Although rare, accurate diagnosis and
      classification of cutaneous smooth muscle proliferations is important as they can
      exhibit a range of clinical behavior and may be associated with underlying
      syndromes. This review summarizes the clinicopathologic spectrum of smooth muscle
      tumors involving the skin.

PMID- 29649002
TI  - JAK1/2 inhibition with baricitinib in the treatment of autoinflammatory
      interferonopathies.
AB  - BACKGROUND: Monogenic IFN-mediated autoinflammatory diseases present in infancy
      with systemic inflammation, an IFN response gene signature, inflammatory organ
      damage, and high mortality. We used the JAK inhibitor baricitinib, with IFN
      blocking activity in vitro, to ameliorate disease. METHODS: Between October 2011
      and February 2017, 10 patients with CANDLE (chronic atypical neutrophilic
      dermatosis with lipodystrophy and elevated temperatures), 4 patients with SAVI
      (stimulator of IFN genes-associated [STING-associated] vasculopathy with onset in
      infancy), and 4 patients with other interferonopathies were enrolled in an
      expanded access program. The patients underwent dose escalation, and the benefit
      was assessed by reductions in daily disease symptoms and corticosteroid
      requirement. Quality of life, organ inflammation, changes in IFN-induced
      biomarkers, and safety were longitudinally assessed. RESULTS: Eighteen patients
      were treated for a mean duration of 3.0 years (1.5-4.9 years). The median daily
      symptom score decreased from 1.3 (interquartile range [IQR], 0.93-1.78) to 0.25
      (IQR, 0.1-0.63) (P < 0.0001). In 14 patients receiving corticosteroids at
      baseline, daily prednisone doses decreased from 0.44 mg/kg/day (IQR, 0.31-1.09)
      to 0.11 mg/kg/day (IQR, 0.02-0.24) (P < 0.01), and 5 of 10 patients with CANDLE
      achieved lasting clinical remission. The patients' quality of life and height and
      bone mineral density Z-scores significantly improved, and their IFN biomarkers
      decreased. Three patients, two of whom had genetically undefined conditions,
      discontinued treatment because of lack of efficacy, and one CANDLE patient
      discontinued treatment because of BK viremia and azotemia. The most common
      adverse events were upper respiratory infections, gastroenteritis, and BK viruria
      and viremia. CONCLUSION: Upon baricitinib treatment, clinical manifestations and
      inflammatory and IFN biomarkers improved in patients with the monogenic
      interferonopathies CANDLE, SAVI, and other interferonopathies. Monitoring safety
      and efficacy is important in benefit-risk assessment. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT01724580 and NCT02974595. FUNDING: This research was
      supported by the Intramural Research Program of the NIH, NIAID, and NIAMS.
      Baricitinib was provided by Eli Lilly and Company, which is the sponsor of the
      expanded access program for this drug.

PMID- 29649003
TI  - Somatic mutation of the cohesin complex subunit confers therapeutic
      vulnerabilities in cancer.
AB  - A synthetic lethality-based strategy has been developed to identify therapeutic
      targets in cancer harboring tumor-suppressor gene mutations, as exemplified by
      the effectiveness of poly ADP-ribose polymerase (PARP) inhibitors in BRCA1/2
      mutated tumors. However, many synthetic lethal interactors are less reliable due
      to the fact that such genes usually do not perform fundamental or indispensable
      functions in the cell. Here, we developed an approach to identifying the
      "essential lethality" arising from these mutated/deleted essential genes, which
      are largely tolerated in cancer cells due to genetic redundancy. We uncovered the
      cohesion subunit SA1 as a putative synthetic-essential target in cancers carrying
      inactivating mutations of its paralog, SA2. In SA2-deficient Ewing sarcoma and
      bladder cancer, further depletion of SA1 profoundly and specifically suppressed
      cancer cell proliferation, survival, and tumorigenic potential. Mechanistically,
      inhibition of SA1 in the SA2-mutated cells led to premature chromatid separation,
      dramatic extension of mitotic duration, and consequently, lethal failure of cell
      division. More importantly, depletion of SA1 rendered those SA2-mutated cells
      more susceptible to DNA damage, especially double-strand breaks (DSBs), due to
      reduced functionality of DNA repair. Furthermore, inhibition of SA1 sensitized
      the SA2-deficient cancer cells to PARP inhibitors in vitro and in vivo, providing
      a potential therapeutic strategy for patients with SA2-deficient tumors.

PMID- 29649006
TI  - The Influence of Volume and Anatomic Location of Optic Disc Drusen on the
      Sensitivity of Autofluorescence.
AB  - BACKGROUND: Optic disc drusen (ODD) are acellular deposits in the optic nerve
      head. ODD can be diagnosed using different imaging modalities, including enhanced
      depth imaging optical coherence tomography (EDI-OCT) and autofluorescence (AF).
      It is unknown which factors determine the sensitivity of AF. The aim of this
      study was to investigate the effect of volume and anatomic location of ODD on the
      sensitivity of AF. METHODS: Cross-sectional study. RESULTS: A total of 38
      patients (75 eyes) with ODD were included. In 12 of 75 eyes (16%) and in 11 of 38
      patients (29%), EDI-OCT detected ODD that were not detected by AF. In 24
      distinctly solitary ODD, both increase in ODD volume (P = 0.0388) and a more
      superficial ODD location (P < 0.0001) increased the possibility of AF detection
      of ODD, when performing a multivariate analysis. CONCLUSIONS: EDI-OCT is superior
      to AF in the diagnosis of ODD. Volume and anatomic location of ODD have a
      significant impact on the sensitivity of AF.

PMID- 29649007
TI  - Practice of Teledermatopathology: A Systematic Review.
AB  - INTRODUCTION: Teledermatopathology has the potential to revolutionize the
      practice of diagnosing skin diseases. This review provides an overview of the
      advantages, limitations, and future directions of teledermatopathology. METHODS:
      MEDLINE was searched via PubMed and Google Scholar databases for relevant
      articles published from 2012 to the present. Additional articles were also
      identified by hand-searching. RESULTS: A total of 2675 citations were identified
      in the initial search. Two thousand five hundred seventy-three were excluded
      based on duplicates and review of titles and abstracts. Eighty studies failed to
      meet the inclusion criteria, resulting in a total of 22 articles for analysis.
      Nine additional articles were hand-searched. CONCLUSIONS: Recent studies report
      that telepathology increases access to specialists, reduces interpretive errors
      and health care expenditures, improves the efficiency of workflow, and optimizes
      patient outcomes. It also facilitates international collaboration by widening
      global access to dermatopathology services and providing educational resources in
      underserved areas. However, the quality and regulations of digital slide imaging
      in teledermatopathology need to be improved.

PMID- 29649008
TI  - Disseminated Granulomatous Perifollicular Dermatosis With Comedones: A Follicular
      Variant of Lichen Nitidus or a New Entity?
AB  - The presence of acquired generalized keratotic follicular papules and comedones
      developing in adulthood constitute an uncommon clinical situation. Although this
      clinical presentation has been described in several noninflammatory,
      inflammatory, and neoplastic skin disorders, its association with an exclusive
      perifollicular epitheliod or granulomatous inflammatory reaction represents an
      exceedingly rare phenomenon. We report a case of a 57-year-old male patient
      presenting clinically numerous acquired disseminated follicular papules and
      comedones, showing isolated perifollicular sarcoid-like granulomatous
      inflammatory infiltrates at the histological examination. These lesions
      experienced a complete spontaneous resolution after several months. The
      possibility that this disseminated, epithelioid, granulomatous, perifollicular
      dermatosis may represent an isolated follicular variant of lichen nitidus or a
      previously nonreported skin disorder is discussed.

PMID- 29649009
TI  - Papular Lesion on the Knee of a 7-Year-Old Girl.

PMID- 29649011
TI  - Ultrasonographic Findings in a Latissimus Dorsi Injury in a Beach Volleyball
      Player.

PMID- 29649012
TI  - Clinical Improvements Are Not Explained by Changes in Tendon Structure on
      Ultrasound Tissue Characterization After an Exercise Program for Patellar
      Tendinopathy.
AB  - OBJECTIVES: The aim of this study was to investigate the effects of a 4-wk in
      season exercise program of isometric or isotonic exercises on tendon structure
      and dimensions as quantified by ultrasound tissue characterization (UTC). DESIGN:
      This was a randomized clinical trial. Volleyball and basketball players (16-31
      yrs, n = 29) with clinically diagnosed patellar tendinopathy were randomized to a
      4-wk isometric or isotonic exercise program. The programs were designed to
      decrease patellar tendon pain. A baseline and 4-wk UTC scan was used to evaluate
      change in tendon structure. RESULTS: No significant change in tendon structure or
      dimensions on UTC was detected after the exercise program despite patellar
      tendinopathy symptoms improving. The percentage and mean cross-sectional area of
      aligned fibrillar structure (echo types I + II) (Z = -0.414, P = 0.679) as well
      as disorganized structure (echo types III + IV) (Z = -0.370, P = 0.711) did not
      change over the 4-wk exercise program. Change in tendon structure and dimensions
      on UTC did not differ significantly between the groups. CONCLUSION: Structural
      properties and dimensions of the patellar tendon on UTC did not change after a 4
      wk isometric or isotonic exercise program for athletes with patellar tendinopathy
      in-season, despite an improvement in symptoms. It seems that structural
      improvements are not required for a positive clinical outcome.

PMID- 29649013
TI  - EEG Patterns in Patients With Calcified Neurocysticercosis With or Without
      Hippocampal Atrophy.
AB  - PURPOSE: To assess whether hippocampal atrophy develops in conjunction with
      clinical or subclinical epileptiform or encephalopathic activity in subjects with
      neurocysticercosis (NCC). METHODS: Using a population-based and nested case
      control study design, scalp EEGs and brain MRIs were performed in Atahualpa
      residents aged >=40 years, who have imaging-confirmed NCC (case patients), as
      well as in age- and sex-matched NCC-free control subjects. RESULTS: Sixty-two
      case patients and 62 control subjects were included. Encephalopathic EEG patterns
      were more common in five NCC subjects with epilepsy than in those without a
      history of seizures. Epileptiform EEG activity was noted in one patient with NCC
      but in none of the control subjects. This subject's focal epileptiform discharges
      correlated with the location of calcified cysticerci in the brain parenchyma, and
      the hippocampus ipsilateral to the epileptiform discharges was more atrophic than
      the contralateral hippocampus. The degree of hippocampal atrophy in patients with
      NCC without a history of seizures was significantly greater than in control
      subjects (P < 0.01) and tended to be even greater in patients with NCC with a
      history of seizures. CONCLUSIONS: Hippocampal atrophy may not be exclusively
      related to seizure activity in patients with NCC. Other mechanisms, such as
      recurrent bouts of inflammation around calcified cysticerci, might explain the
      association between NCC and hippocampal atrophy.

PMID- 29649014
TI  - Structural MRI Correlates of Cognitive Event-Related Potentials in Multiple
      Sclerosis.
AB  - PURPOSE: Cognitive impairment in multiple sclerosis has been associated with
      cognitive event-related potentials and MRI abnormalities. This study aims to
      explore for the first time the association between P300 and MRI in multiple
      sclerosis. METHODS: Fifty-eight relapsing-remitting patients (41.5 +/- 10.5 years
      old, 41 women, disease duration 139.7 +/- 84.9 months) and 51 healthy controls
      were used. Visual P300 responses and a set of 2- or 3-dimensional MRI indices
      were obtained. Neuropsychological testing and psychological evaluations were also
      performed. RESULTS: Multiple sclerosis patients had significantly lower P300
      amplitude and more prolonged P300 latencies and reaction times than healthy
      controls. In total, 67.2% of patients were identified with abnormal P300
      response. These patients had greater disability and physical fatigue and had
      lower visuospatial memory scores than those with normal P300 response. Abnormally
      low P300 amplitude was associated with lower peripheral gray matter volume and
      was correlated only with normalized frontal horn width and normalized brain
      volume, after adjusting for age and education. The moderating role of brain
      reserve was also documented. CONCLUSIONS: P300 event-related potential was
      related to both linear and volumetric MRI markers. Future studies should expand
      these results in other disease types and longitudinally. Event-related potentials
      could serve as an ancillary tool for cognitive assessment in multiple sclerosis.

PMID- 29649015
TI  - Validation of the 5-Item Medication Adherence Report Scale in Older Stroke
      Patients in Iran.
AB  - BACKGROUND: There is a lack of feasible and validated measures to self-assess
      medication adherence for older patients with stroke. In addition, the potential
      determinants of medication adherence for older patients with stroke remain
      unclear. OBJECTIVES: The aims of this study were to (1) examine the psychometric
      properties of a 5-item questionnaire on medication adherence, specifically the 5
      item Medication Adherence Report Scale (MARS-5), and (2) explore the determinants
      of medication adherence. METHODS: Stroke patients older than 65 years (N = 523)
      filled out the MARS-5 and the Hospital Anxiety and Depression Scale. The
      medication possession rate (MPR) was calculated to measure the objective
      medication adherence. Several clinical characteristics (stroke types, blood
      pressure, comorbidity, HbA1c, quantity of prescribed drugs, fasting blood
      glucose, and total cholesterol) and background information were collected. We
      used Rasch analysis with a differential item functioning test to examine
      psychometric properties. RESULTS: All 5 items in the MARS-5 fit in the same
      construct (ie, medication adherence), no differential item functioning items were
      displayed in the MARS-5 across gender, and the MARS-5 total score was strongly
      correlated with the MPR (r = 0.7). Multiple regression models showed that the
      MARS-5 and the MPR shared several similar determinants. In addition, the variance
      of the MARS-5 (R = 0.567) was more than that of the MPR (R = 0.300). CONCLUSIONS:
      The MARS-5 is a feasible and valid self-assessed medication adherence for older
      patients with stroke. In addition, several determinants were found to be related
      to medication adherence for older patients with stroke. Healthcare providers may
      want to take heed of these determinants to improve medication adherence for this
      population.

PMID- 29649016
TI  - Thyroid cancer management: from a suspicious nodule to targeted therapy.
AB  - Thyroid nodules are very common, and their frequency is four to five times higher
      in women than in men. Most of them are benign, with only a very little percentage
      revealing a malignant neoplasm. About 50% of thyroid nodules are detected by self
      palpation of neck, whereas the other 50% are diagnosed by neck ultrasonography
      and following fine-needle aspiration. Management of thyroid nodules is very
      difficult, because benign nodules are prevalent, whereas thyroid carcinoma is
      uncommon, representing only 1% of all malignancies. A standard diagnostic
      approach is represented by 'first-level' exams, consisting in neck
      ultrasonography and serum thyroid-stimulating hormone measurement, followed, only
      for nodules that are suspicious of malignancy, by 'second-level' exams,
      consisting of fine-needle aspiration and mutational test, which does detect
      particular DNA mutations present only in malignant cells. In this review, we will
      analyze the genetics of thyroid cancer and its heterogeneity, and we will briefly
      describe the current available diagnostic and therapeutic approaches.

PMID- 29649017
TI  - A Point-based Histologic Scoring System for Hepatocellular Carcinoma Can Stratify
      Risk of Posttransplant Tumor Recurrence.
AB  - Eligibility for liver transplant is most commonly decided by measuring tumor size
      and number on radiographic imaging. However, this method often underestimates the
      extent of disease. Evaluation of tumor histology has been shown to improve risk
      stratification when compared with imaging-based transplant criteria, but the
      World Health Organization (WHO) guidelines for grading hepatocellular carcinoma
      (HCC) are imprecise and require subjective interpretation by the pathologist. We
      performed a retrospective analysis of 190 explanted livers containing HCC and
      correlated histologic features with posttransplant recurrence to formulate a
      three-tiered, point-based scoring system that categorizes tumors as having a low,
      intermediate, or high risk of recurrence. Our Recurrence Risk Assessment Score
      (RRAS) evaluates tumor architecture and specific cytologic features-nuclear
      pleomorphism, cytoplasmic amphophilia, and nuclear-to-cytoplasmic ratio-showing
      superior stratification of HCC recurrence risk compared with imaging criteria and
      grade assigned by WHO methodology. Stratifying tumors using RRAS criteria, the
      rate of recurrence after transplant was 0% among low-risk tumors (compared with
      3% of well-differentiated tumors), 12% among intermediate-risk tumors (compared
      with 15% of moderately differentiated tumors), and 54% among high-risk tumors
      (compared with 29% of poorly differentiated tumors). Receiver operating
      characteristic analysis shows significantly improved performance of RRAS criteria
      in predicting HCC recurrence compared with WHO grade (area under curve of 0.841
      and 0.671, respectively; P=0.0061). Our results indicate that evaluation of tumor
      histology offers superior prediction of recurrence risk following liver
      transplantation compared with radiographic criteria, and that the RRAS system
      better stratifies recurrence risk compared with HCC grading by WHO methodology.

PMID- 29649018
TI  - Frequency of MAP2K1, TP53, and U2AF1 Mutations in BRAF-mutated Langerhans Cell
      Histiocytosis: Further Characterizing the Genomic Landscape of LCH.
AB  - Langerhans cell histiocytosis is a proliferative disorder of neoplastic
      Langerhans cells with activating mutations in the Erk signaling pathway. TP53 and
      U2AF1 mutations have been implicated in other myelomonocytic malignancies and we
      hypothesized that mutations in these genes may cosegregate in LCH patients
      according to BRAF mutation status. Towards this end, we collected cases with a
      pathologic diagnosis of Langerhans cell histiocytosis from Stanford University
      Hospital. We analyzed the status of known pathogenic alleles in BRAF, ARAF, TP53,
      U2AF1, and MAP2K1 on formalin-fixed, paraffin-embedded tissue by direct
      sequencing. A total of 41 cases (71%) had a BRAFV600E allele detected by
      sequencing. MAP2K1 mutations were also detected in 5 cases: 3 of 17 (18%) cases
      with wild-type BRAF and 2 of 41 (5%) cases with BRAFV600E mutations (P=0.14). No
      cases contained the previously reported ARAF mutation, Q347_A348del. All 10 cases
      with TP53 mutations contained mutant BRAFV600E allele (P=0.021). Of the 11 cases
      with U2AF1 mutated, 9 of 41 cases co-occurred with BRAFV600E mutations (P=0.31)
      and 2 of 17 with wild-type BRAF. Interestingly, we do not find that somatic
      activating MAP2K1 mutations are mutually exclusive with BRAFV600E mutations as
      has been reported previously. Instead, our data suggests that MAP2K1 mutations
      may be present along with BRAF either at diagnosis or may be acquired during
      disease progression. Furthermore, we demonstrated that likely deleterious TP53
      mutations correlate with BRAF mutational status and may play a role in the
      underlying pathogenesis.

PMID- 29649019
TI  - NUT Carcinoma of the Salivary Glands: Clinicopathologic and Molecular Analysis of
      3 Cases and a Survey of NUT Expression in Salivary Gland Carcinomas.
AB  - NUT carcinoma (NC) represents a rare subset of highly aggressive poorly
      differentiated carcinomas characterized by rearrangement of the NUT (aka NUTM1,
      nuclear protein in testis) gene, most commonly fused to BRD4. Originally
      described as a mediastinal/thymic malignancy, NC has been reported at a variety
      of anatomic regions including the upper and lower aerodigestive tract. To date,
      only 7 NC cases of probable salivary gland origin have been reported. We herein
      describe 3 new cases (all affecting the parotid gland) in 2 women (39- and 55-y
      old) and 1 man (35-y old). Histologic examination showed poorly differentiated
      neoplasms composed of poorly cohesive small-sized to medium-sized cells with
      variable squamoid cell component that was focal and abrupt. Immunohistochemistry
      showed uniform expression of p63 and distinctive punctate expression of the NUT
      antigen in the tumor cell nuclei. Review of the reported salivary gland NC cases
      (total, 10) showed a male:female ratio of 1.5:1 and an age range of 12 to 55
      years (median, 29 y). Site of the primary tumor was the parotid (7), sublingual
      (2), and submandibular (1) glands. All presented as rapidly growing masses
      treated by surgery followed by adjuvant radiotherapy/chemotherapy. Initial nodal
      status was positive in 8/10. At last follow-up (1 to 24 mo; median, 5 mo), 7/10
      patients died of disease at a median of 5.5 months (1 to 24 mo) and only 2 were
      disease free at 7 and 14 months. Of 9 cases with genetic data, the fusion partner
      was BRD4 (n=7), non-BRD4/3 (n=1), or undetermined (n=1). None of 306 carcinomas
      spanning the spectrum of salivary carcinoma types screened by NUT
      immunohistochemistry was positive. This is the first small series on salivary NC
      highlighting the importance to include this rare disease in the differential
      diagnosis of poorly differentiated salivary gland carcinomas and in cases of
      presumable poorly differentiated carcinoma of unknown origin.

PMID- 29649020
TI  - Autologous Bone Flap Resorption Years After Subtemporal Craniotomy.
AB  - In Spring of 2012, the partially undressed and skeletonized remains of a homeless
      adult Hispanic male was found in a fairly open wooded area in Nebraska. The
      remains showed evidence of extensive pathologies, which included healed traumas
      and surgeries. Examination of the decedent's medical records revealed that he had
      a history of kidney and liver problems, alcohol abuse, several traumas including
      a major head injury that necessitated a craniotomy, and radiological features of
      neurocysticercosis. The autologous bone flap, which was replaced after the
      craniotomy, had resorbed significantly away from the edges of the injury. Death
      was variously attributed to craniocerebral injury with hypothermia sequel to
      blunt force trauma most probably due to a fall. The manner of death was ruled as
      an accident. This study makes use of the forensic evidence and medical records to
      examine the possibility that the unique combination of failed cranioplasty,
      hypothermia, and neurocysticercosis may have contributed to the victim's death.
      Other potential causes of death are considered.

PMID- 29649021
TI  - Impressions of Early Mobilization of Critically Ill Children-Clinician, Patient,
      and Family Perspectives.
AB  - OBJECTIVES: To understand patient, family caregiver, and clinician impressions of
      early mobilization, the perceived barriers and facilitators to its
      implementation, and the use of in-bed cycling as a method of mobilization.
      DESIGN: A qualitative study, conducted as part of the Early Exercise in
      Critically ill Youth and Children, a preliminary Evaluation (wEECYCLE) Pilot
      randomized controlled trial. SETTING: McMaster Children's Hospital PICU,
      Hamilton, ON, Canada. PARTICIPANTS: Clinicians (i.e., physicians, nurses, and
      physiotherapists), family caregivers, and capable patients age greater than or
      equal to 8 years old who were enrolled in a clinical trial of early mobilization
      in critically ill children (wEECYCLE). INTERVENTION: Semistructured, face-to-face
      interviews using a customized interview guide for clinicians, caregivers, and
      patients respectively, conducted after exposure to the early mobilization
      intervention. MEASUREMENTS AND MAIN RESULTS: Thirty-seven participants were
      interviewed (19 family caregivers, four patients, and 14 clinicians). Family
      caregivers and clinicians described similar interrelated themes representing
      barriers to mobilization, namely low prioritization of mobilization by the
      medical team, safety concerns, the lack of physiotherapy resources, and low
      patient motivation. Key facilitators were family trust in the healthcare team,
      team engagement, an a priori belief that physical activity is important, and
      participation in research. Increased familiarity and specific features such as
      the virtual reality component and ability to execute passive and or active
      mobilization helped to engage critically ill children in in-bed cycling.
      CONCLUSIONS: Clinicians, patients, and families were highly supportive of
      mobilization in critically ill children; however, concerns were identified with
      respect to how and when to execute this practice. Understanding key stakeholder
      perspectives enables the development of strategies to facilitate the
      implementation of early mobilization and in-bed cycling, not just in the context
      of a clinical trial but also within the culture of practice in a PICU.

PMID- 29649022
TI  - Effectiveness of Chinese Martial Arts and Philosophy to Reduce Reactive and
      Proactive Aggression in Schoolchildren.
AB  - OBJECTIVE: This study examined the effectiveness of Chinese martial arts in
      reducing reactive and proactive aggressive behavior among schoolchildren with a
      cluster-randomized trial. METHODS: A screening questionnaire was completed by
      3511 schoolchildren of Grades 2 to 5 from 13 sites in Hong Kong. We shortlisted
      298 children who scored z >= 1 on the total score of the Reactive-Proactive
      Aggression Questionnaire in their respective sites to participate in the
      experiment. They were divided into 31 clusters that were blinded and randomly
      assigned to one of the 4 conditions: skills only, philosophy only, skills and
      philosophy, and physical fitness (placebo). Subjects were assessed at baseline,
      posttraining, and 6 months after training using aggression scales. RESULTS:
      Results from the linear mixed model indicated that the time * training
      interaction effects were significant for aggressive behavior (reactive and
      proactive), delinquent behavior, anxiety/depression, and attention problems.
      Although all measures declined in all conditions over time, only the skills-and
      philosophy condition showed a significant reduction at posttraining and/or 6
      month follow-up compared with the placebo. CONCLUSION: The results provided a
      theoretical proof for the relationship between aggression and sport involvement
      combined with children's moral reasoning. This study gives practical implications
      to intervention that solely playing sports or teaching moral lessons is not
      effective enough for high-risk schoolchildren with aggressive behavior. However,
      combined traditional Chinese martial arts skills and moral philosophy training
      could be considered in the school curriculum to reduce school violence and
      facilitate creation of harmonious schools.

PMID- 29649024
TI  - World Gastroenterology Organisation (WGO) News and Events.

PMID- 29649023
TI  - Helping a Child with Autism Spectrum Disorder Cope with Divorce.
AB  - CASE: Aaron is an 11-year-old boy with autism spectrum disorder (ASD), with
      cognitive and language skills in the above-average range, whose parents have
      recently separated. Aaron's mother initiated the separation when she learned that
      Aaron's father had maintained a relationship with a woman with whom he has a 10
      year-old daughter. When Aaron's mother discovered this relationship, she demanded
      that Aaron's father leave their home.Aaron's father has moved in with his long
      term girlfriend and keeps in contact with Aaron by calling once a day. Neither
      Aaron's father nor mother has discussed the reason for their separation with
      Aaron. So far, they have explained their separation by telling Aaron that they
      are "taking a break."Aaron's mother has been deeply hurt by Aaron's father's
      infidelity and does not want to reconcile with him. Aaron's father recognizes
      this but would like to continue to have a close relationship with his son. He
      would also like Aaron to get to know his half-sister.Aaron's mother seeks
      guidance regarding how to talk to Aaron about the separation and his father's
      second family. Given Aaron's diagnosis of ASD, she is particularly concerned
      about his ability to cope with this unexpected change in circumstances. What is
      your advice?

PMID- 29649025
TI  - Risk of Anal Cancer in Women With a Human Papillomavirus-Related Gynecological
      Neoplasm: Puerto Rico 1987-2013.
AB  - OBJECTIVE: The aim of the study was to estimate the magnitude of the association
      between HPV-related gynecological neoplasms and secondary anal cancer among women
      in Puerto Rico (PR). MATERIALS AND METHODS: We identified 9,489 women who had
      been diagnosed with a primary cervical, vaginal, or vulvar tumor during 1987
      2013. To describe the trends of invasive cervical, vulvar, vaginal, and anal
      cancer, the age-adjusted incidence rates were estimated using the direct method
      (2000 US as Standard Population). Standardized incidence ratios
      (observed/expected) were computed using the indirect method; expected cases were
      calculated using 2 methods based on age-specific rates of anal cancer in PR. The
      ratio of standardized incidence ratios of anal cancer was estimated using the
      Poisson regression model to estimate the magnitude of the association between HPV
      gynecologic neoplasms and secondary anal cancer. RESULTS: A significant increase
      in the incidence trend for anal cancer was observed from 1987 to 2013 (annual
      percent change = 1.1, p < .05), whereas from 2004 to 2013, an increase was
      observed for cervical cancer incidence (annual percent change = 3.3, p < .05).
      The risk of secondary anal cancer among women with HPV-related gynecological
      cancers was approximately 3 times this risk among women with non-HPV-related
      gynecological cancers (relative risk = 3.27, 95% CI = 1.37 to 7.79). CONCLUSIONS:
      Anal cancer is increasing among women in PR. Women with gynecological HPV-related
      tumors are at higher risk of secondary anal cancer as compared with women from
      the general population and with those with non-HPV-related gynecological cancers.
      Appropriate anal cancer screening guidelines for high-risk populations are
      needed, including women with HPV-related gynecological malignancies and
      potentially other cancer survivors.

PMID- 29649026
TI  - Evidence Review Conducted for the Agency for Healthcare Research and Quality
      Safety Program for Improving Surgical Care and Recovery: Focus on Anesthesiology
      for Colorectal Surgery.
AB  - The Agency for Healthcare Research and Quality, in partnership with the American
      College of Surgeons and the Johns Hopkins Medicine Armstrong Institute for
      Patient Safety and Quality, has developed the Safety Program for Improving
      Surgical Care and Recovery (ISCR), which is a national effort to disseminate best
      practices in perioperative care to more than 750 hospitals across multiple
      procedures in the next 5 years. The program will integrate evidence-based
      processes central to enhanced recovery and prevention of surgical site infection,
      venous thromboembolic events, catheter-associated urinary tract infections with
      socioadaptive interventions to improve surgical outcomes, patient experience, and
      perioperative safety culture. The objectives of this review are to evaluate the
      evidence supporting anesthesiology components of colorectal (CR) pathways and to
      develop an evidence-based CR protocol for implementation. Anesthesiology protocol
      components were identified through review of existing CR enhanced recovery
      pathways from several professional associations/societies and expert feedback.
      These guidelines/recommendations were supplemented by evidence made further
      literature searches. Anesthesiology protocol components were identified spanning
      the immediate preoperative, intraoperative, and postoperative phases of care.
      Components included carbohydrate loading, reduced fasting, multimodal
      preanesthesia medication, antibiotic prophylaxis, blood transfusion,
      intraoperative fluid management/goal-directed fluid therapy, normothermia, a
      standardized intraoperative anesthesia pathway, and standard postoperative
      multimodal analgesic regimens.

PMID- 29649027
TI  - Pain and Its Long-term Interference of Daily Life After Critical Illness.
AB  - BACKGROUND: Persistent pain likely interferes with quality of life in survivors
      of critical illness, but data are limited on its prevalence and risk factors. We
      sought to determine the prevalence of persistent pain after critical illness and
      its interference with daily life. Additionally, we sought to determine if
      intensive care unit (ICU) opioid exposure is a risk factor for its development.
      METHODS: In a cohort of adult medical and surgical ICU survivors, we used the
      brief pain inventory (BPI) to assess pain intensity and pain interference of
      daily life at 3 and 12 months after hospital discharge. We used proportional odds
      logistic regression with Bonferroni correction to evaluate the independent
      association of ICU opioid exposure with BPI scores, adjusting for potential
      confounders including age, preadmission opioid use, frailty, surgery, severity of
      illness, and durations of delirium and sepsis while in the ICU. RESULTS: We
      obtained BPI outcomes in 295 patients overall. At 3 and 12 months, 77% and 74% of
      patients reported persistent pain symptoms, respectively. The median
      (interquartile range) pain intensity score was 3 (1, 5) at both 3 and 12 months.
      Pain interference with daily life was reported in 59% and 62% of patients at 3
      and 12 months, respectively. The median overall pain interference score was 2 (0,
      5) at both 3 and 12 months. ICU opioid exposure was not associated with increased
      pain intensity at 3 months (odds ratio [OR; 95% confidence interval], 2.12 [0.92
      4.93]; P = .18) or 12 months (OR, 2.58 [1.26-5.29]; P = .04). ICU opioid exposure
      was not associated with increased pain interference of daily life at 3 months
      (OR, 1.48 [0.65-3.38]; P = .64) or 12 months (OR, 1.46 [0.72-2.96]; P = .58).
      CONCLUSIONS: Persistent pain is prevalent after critical illness and frequently
      interferes with daily life. Increased ICU opioid exposure was not associated with
      worse pain symptoms. Further studies are needed to identify modifiable risk
      factors for persistent pain in the critically ill and the effects of ICU opioids
      on patients with and without chronic pain.

PMID- 29649028
TI  - Does the Incidence of Postoperative Complications After Inguinal Hernia Repair
      Justify Hospital Admission in Prematurely and Term Born Infants?
AB  - BACKGROUND: Postoperatively, young infants are admitted overnight in view of the
      risk for respiratory complications such as desaturation and apnea. This risk
      seems much lower than previously reported. Until what age this risk persists, and
      which infants might actually qualify for day-care treatment, is unknown. METHODS:
      We retrospectively reviewed medical charts from preterm infants <45 weeks
      postconceptional age (PCA), 45-60 weeks PCA, and term infants <3 months admitted
      overnight after inguinal hernia repair, from January 2011 to December 2015 in a
      large tertiary children's hospital. Postoperative complications (divided into
      respiratory, circulatory, neurologic, and other), recurrence, and reoperation
      were documented and compared between groups. RESULTS: Medical charts of 485
      patients were reviewed. Postoperative respiratory complications (mainly
      desaturations or apnea) had been documented for 27 of 76 (35.5%) preterm infants
      <45 weeks PCA, for 13 of 221 (5.9%) preterm infants 45-60 weeks PCA, and for 3 of
      188 (1.6%) term infants (P < .001). An analysis of the 221 preterm infants 45-60
      weeks PCA showed statistically significantly more respiratory complications in 76
      infants with a respiratory history (eg, bronchopulmonary dysplasia) compared with
      the others (respectively 13.2% vs 0.7%; P < .001). In these infants, lower
      gestational age at the time of surgery was statistically significantly predictive
      for the development of respiratory complications (odds ratio [OR], 0.68 [95%
      confidence interval {CI}, 0.52-0.89]; P = .005), but respiratory history (OR,
      3.50 [0.34-36.28]; P = .294) and American Society of Anesthesiologists (ASA)
      physical status (OR, 1.54 [95% CI, 0.31-7.65]; P = .598 for ASA physical status
      II and OR, 6.11 [95% CI, 0.76-49.05]; P = .089 for ASA physical status III) were
      not predictive. CONCLUSIONS: Incidence of postoperative respiratory complications
      is high in preterm infants <45 weeks PCA requiring postoperative overnight
      saturation and heart rate monitoring. Incidence of postoperative complications in
      preterm born infants 45-60 weeks PCA varies. Gestational age and possibly
      presence of respiratory history can be used to estimate the need for overnight
      admission in these infants. Postoperative respiratory complications after
      inguinal hernia repair in ASA physical status I and II term born infants >1 month
      of age are uncommon, which justifies day-care admission for this type of surgical
      procedure.

PMID- 29649029
TI  - Dexmedetomidine Sedation for Paroxysmal Supraventricular Tachycardia Ablation Is
      Not Associated With Alteration of Arrhythmia Inducibility.
AB  - BACKGROUND: Dexmedetomidine (Dex) is an attractive agent for procedural sedation
      due to its unique pharmacodynamic profile, specifically affording predictable
      sedation without concurrent respiratory depression. However, Dex has previously
      been reported to prevent or terminate arrhythmias. The purpose of this study was
      to investigate paroxysmal supraventricular tachycardia (PSVT) inducibility and
      homeostatic stability during electrophysiology studies (EPSs) and ablation when a
      standardized Dex protocol was used as the primary sedation agent. METHODS: We
      performed a retrospective review of 163 consecutive procedures for PSVT ablation
      that received Dex as the primary sedative with adjunct fentanyl and midazolam
      boluses (DEX-FENT-MIDAZ). This cohort was compared to 163 consecutive control
      procedures wherein strictly fentanyl and midazolam were used for sedation. The
      primary outcome reviewed was PSVT inducibility assessed before ablation. Reviewed
      secondary outcomes included level of sedation and intraprocedure hemodynamics and
      oxygenation. RESULTS: The arrhythmia profiles of the DEX-FENT-MIDAZ and control
      cohorts were very similar. The overall incidence of a "negative" EPSs in which
      arrhythmia was not induced was 24% in the DEX-FENT-MIDAZ group and 26% in the
      control group (P = .7). Unintended deep sedation was significantly less with DEX
      FENT-MIDAZ (4.3% vs 27%; P <= .0001). However, DEX-FENT-MIDAZ use was associated
      with a higher incidence of intraprocedure hypotension. CONCLUSIONS: Dex sedation
      during EPSs is not associated with a reduction in PSVT inducibility. The
      therapeutic utility of Dex during EPS arises from the predictable sedation Dex
      affords but is associated with an increased incidence of intraprocedure
      hypotension.

PMID- 29649030
TI  - Resistin Is a Novel Marker for Postoperative Pain Intensity.
AB  - BACKGROUND: Pro- and anti-inflammatory cytokines (adipokines) associated with
      adipose tissue can modulate inflammatory processes and lead to systemic
      inflammatory conditions such as metabolic syndrome. In the present pilot study,
      we investigated 3 major adipokines (leptin, adiponectin, and resistin) and 2
      nonspecific proinflammatory cytokines (tumor necrosis factor alpha and
      interleukin-6) with regard to their association with postoperative pain
      intensity. METHODS: We analyzed a total of 45 single-nucleotide polymorphisms of
      the adipokines in 57 patients with postlaparotomy pain. We adjusted for multiple
      testing to reduce the chance of false-positive results by controlling the false
      discovery rate. Serum levels of the adipokines and proinflammatory cytokines were
      measured in another 36 patients undergoing laparotomy. A stepwise multiple linear
      regression analysis using these measurements and opioid dosages as independent
      variables was performed to explore the factors associated with postoperative
      pain. RESULTS: Only 1 variant of the resistin gene (rs3745367) demonstrated a
      significant association with postoperative pain (P < .002). Patients exhibiting
      homozygosity for the minor alleles (n = 7; numerical rating scale [NRS], 2.3 +/-
      1.3) demonstrated lower pain intensity compared with those exhibiting
      homozygosity for the major alleles (n = 29; NRS, 3.8 +/- 1.0; P = .004) and
      heterozygosity for the minor alleles (n = 21; NRS, 4.2 +/- 0.8; P < .001). Only
      serum resistin levels showed a positive association with postoperative pain.
      CONCLUSIONS: A genetic variant of resistin and serum resistin levels were
      associated with postoperative pain intensity, while other adipokines and
      cytokines exhibit no such association. Resistin can alter the inflammatory
      responses in postoperative wounds, although it could be a determinant factor that
      is independent of inflammatory processes. Resistin may be a novel marker for
      postoperative pain intensity.

PMID- 29649031
TI  - Low Level of Vegetative State After Traumatic Brain Injury in a Swiss Academic
      Hospital.
AB  - BACKGROUND: No standards exist regarding decision making for comatose patients,
      especially concerning life-saving treatments. The aim of this retrospective,
      single-center study was to analyze outcomes and the decision-making process at
      the end of life (EOL) in patients with traumatic brain injury (TBI) in a Swiss
      academic tertiary care hospital. METHODS: Consecutive admissions to the surgical
      intensive care unit (ICU) with stays of at least 48 hours between January 1, 2012
      and June 30, 2015 in patients with moderate to severe TBI and with fatality
      within 6 months after trauma were included. Descriptive statistics were used.
      RESULTS: Of 994 ICU admissions with TBI in the study period, 182 had an initial
      Glasgow Coma Scale <13 and a length of stay in the ICU >48 hours. For 174 of
      them, a 6-month outcome assessment based on the Glasgow Outcome Scale (GOS) was
      available: 43.1% (36.0%-50.5%) had favorable outcomes (GOS 4 or 5), 28.7% (22.5%
      35.9%) a severe disability (GOS 3), 0.6% (0%-3.2%) a vegetative state (GOS 2),
      and 27.6% (21.5%-34.7%) died (GOS 1). Among the GOS 1 individuals, 45 patients
      had a complete dataset (73% men; median age, 67 years; interquartile range, 43-79
      years). Life-prolonging therapies were limited in 95.6% (85.2%-99.2%) of the
      cases after interdisciplinary prognostication and involvement of the surrogate
      decision maker (SDM) to respect the patient's documented or presumed will. In
      97.7% (87.9%-99.9%) of the cases, a next of kin was the SDM and was involved in
      the EOL decision and process in 100% (96.3%-100.0%) of the cases. Written advance
      directives (ADs) were available for 14.0% (6.6%-27.3%) of the patients, and 34.9%
      (22.4%-49.8%) of the patients had shared their EOL will with relatives before
      trauma. In the other cases, each patient's presumed will was acknowledged after a
      meeting with the SDM and was binding for the EOL decision. CONCLUSIONS: At our
      institution, the majority of deaths after TBI follow a decision to limit life
      prolonging therapies. The frequency of patients in vegetative state 6 months
      after TBI is lower than expected; this could be due to the high prevalence of
      limitation of life-prolonging therapies. EOL decision making follows a
      standardized process, based on patients' will documented in the ADs or on
      preferences assumed by the SDM. The prevalence of ADs was low and should be
      encouraged.

PMID- 29649032
TI  - Airway Management Practice in Adults With an Unstable Cervical Spine: The
      Harborview Medical Center Experience.
AB  - BACKGROUND: Airway management in the presence of acute cervical spine injury
      (CSI) is challenging. Because it limits cervical spine motion during tracheal
      intubation and allows for neurological examination after the procedure, awake
      fiberoptic bronchoscopy (FOB) has traditionally been recommended. However, with
      the widespread availability of video laryngoscopy (VL), its use has declined
      dramatically. Our aim was to describe the frequency of airway management
      techniques used in patients with CSI at our level I trauma center and report the
      incidence of neurological injury attributable to airway management. METHODS:
      Adults presenting to the operating room with CSI without a tracheal tube in situ
      between September 2010 and June 2017 were included. All patients were intubated
      in the presence of manual-in-line stabilization, a hard cervical collar, or
      surgical traction. Worsening neurological status was defined as new motor or
      sensory deficits on postoperative examination. RESULTS: Two hundred fifty-two
      patients were included, of which 76 (30.2%) had preexisting neurological
      deficits. VL was the most frequent initial airway management technique used
      (49.6%). Asleep FOB was commonly performed alone (30.6%) or in conjunction with
      VL (13.5%). Awake FOB was rarely performed (2.3%), as was direct laryngoscopy
      (2.8%). All techniques were associated with high first-attempt success rates, and
      no cases of neurological injury attributable to airway management technique were
      identified. CONCLUSIONS: Among patients with acute CSI at a high-volume academic
      trauma center, VL was the most commonly used initial intubation technique. Awake
      FOB and direct laryngoscopy were performed infrequently. No cases of neurological
      deterioration secondary to airway management occurred with any method. Assuming
      care is taken to limit neck movement, providers should use the intubation
      technique with which they have the most comfort and skill.

PMID- 29649033
TI  - Predictors of Admission After the Implementation of an Enhanced Recovery After
      Surgery Pathway for Minimally Invasive Gynecologic Surgery.
AB  - BACKGROUND: Enhanced recovery after surgery (ERAS) pathways in gynecologic
      surgery have been shown to decrease length of stay with no impact on readmission,
      but no study has assessed predictors of admission in this population. The purpose
      of this study was to identify predictors of admission after laparoscopic
      hysterectomy (LH) and robotic-assisted hysterectomy (RAH) performed under an ERAS
      pathway. METHODS: This is a prospective observational study of women undergoing
      LH/RAH for benign indications within an ERAS pathway. Data collected included
      same-day discharge, reason for admission, incidences of urgent clinic and
      emergency room (ER) visits, readmissions, reoperations, and 9 postulated
      predictors of admission listed below. Patient demographics, markers of baseline
      health, and clinical outcomes were compared between groups (ERAS patients
      discharged on the day of surgery versus admitted) using Fisher exact and Student
      t tests. Multivariable logistic regression was used to assess the potential risk
      factors for being admitted, adjusting for age, race, body mass index, American
      Society of Anesthesiologists (ASA) physical status score, preoperative diagnosis
      indicative of hysterectomy, preoperative chronic pain, completion of a
      preprocedure pain-coping skills counseling session, procedure time, and
      compliance to the ERAS pathway. RESULTS: There were 165 patients undergoing
      LH/RAH within an ERAS pathway; 93 (56%) were discharged on the day of surgery and
      72 were admitted. There were no significant differences in ER visits,
      readmissions, and reoperations between groups (ER visits: discharged 13% versus
      admitted 13%, P = .99; 90-day readmission: discharged 4% versus admitted 7%, P =
      .51; and 90-day reoperation: discharged 4% versus admitted 3%, P = .70). The most
      common reasons for admission were postoperative urinary retention (n = 21, 30%),
      inadequate pain control (n = 21, 30%), postoperative nausea and vomiting (n = 7,
      10%), and planned admissions (n = 7, 10%). Increased ASA physical status, being
      African American, and increased length of procedure were significantly associated
      with an increased risk of admission (ASA physical status III versus ASA physical
      status I or II: odds ratio [OR], 3.12; 95% confidence interval [CI], 1.36-7.16; P
      = .007; African American: OR, 2.47; 95% CI, 1.02-5.96; P = .04; and length of
      procedure, assessed in 30-minute increments: OR, 1.23; 95% CI, 1.02-1.50; P =
      .04). CONCLUSIONS: We were able to define predictors of admission for patients
      having LH/RAH managed with an ERAS pathway. Increased ASA physical status, being
      African American, and increased length of procedure were significantly associated
      with admission after LH/RAH performed under an ERAS pathway. In addition, the
      incidences of urgent clinic and ER visits, readmissions, and reoperations within
      90 days of surgery were similar for patients who were discharged on the day of
      surgery compared to those admitted.

PMID- 29649034
TI  - Obstructive Sleep Apnea in Pregnant Women: A Review of Pregnancy Outcomes and an
      Approach to Management.
AB  - Among obese pregnant women, 15%-20% have obstructive sleep apnea (OSA) and this
      prevalence increases along with body mass index and in the presence of other
      comorbidities. Prepregnancy obesity and pregnancy-related weight gain are
      certainly risk factors for sleep-disordered breathing in pregnancy, but certain
      physiologic changes of pregnancy may also increase a woman's risk of developing
      or worsening OSA. While it has been shown that untreated OSA in postmenopausal
      women is associated with a range of cardiovascular, pulmonary, and metabolic
      comorbidities, a body of literature is emerging that suggests OSA may also have
      serious implications for the health of mothers and fetuses during and after
      pregnancy. In this review, we discuss the following: pregnancy as a vulnerable
      period for the development or worsening of OSA; the associations between OSA and
      maternal and fetal outcomes; the current screening modalities for OSA in
      pregnancy; and current recommendations regarding peripartum management of OSA.

PMID- 29649035
TI  - Pharmacological Characterization of Levorphanol, a G-Protein Biased Opioid
      Analgesic.
AB  - BACKGROUND: Levorphanol is a potent analgesic that has been used for decades.
      Most commonly used for acute and cancer pain, it also is effective against
      neuropathic pain. The recent appreciation of the importance of functional bias
      and the uncovering of multiple u opioid receptor splice variants may help explain
      the variability of patient responses to different opioid drugs. METHODS: Here, we
      evaluate levorphanol in a variety of traditional in vitro receptor binding and
      functional assays. In vivo analgesia studies using the radiant heat tail flick
      assay explored the receptor selectivity of the responses through the use of
      knockout (KO) mice, selective antagonists, and viral rescue approaches. RESULTS:
      Receptor binding studies revealed high levorphanol affinity for all the MU,
      delta, and kappa opioid receptors. In S-GTPgammaS binding assays, it was a full
      agonist at most u receptor subtypes, with the exception of MOR-1O, but displayed
      little activity in beta-arrestin2 recruitment assays, indicating a preference for
      G-protein transduction mechanisms. A KO mouse and selective antagonists confirmed
      that levorphanol analgesia was mediated through classical u receptors, but there
      was a contribution from 6 transmembrane targets, as illustrated by a lower
      response in an exon 11 KO mouse and its rescue with a virally transfected 6
      transmembrane receptor splice variant. Compared to morphine, levorphanol had less
      respiratory depression at equianalgesic doses. CONCLUSIONS: While levorphanol
      shares many of the same properties as the classic opioid morphine, it displays
      subtle differences that may prove helpful in its clinical use. Its G-protein
      signaling bias is consistent with its diminished respiratory depression, while
      its incomplete cross tolerance with morphine suggests it may prove valuable
      clinically with opioid rotation.

PMID- 29649036
TI  - Association Between Alexithymia and Risk of Incident Cardiovascular Diseases in
      the SUpplementation en VItamines et Mineraux AntioXydants (SU.VI.MAX) Cohort.
AB  - OBJECTIVE: Although it has been suggested that alexythymia is associated with
      cardiovascular diseases, studies are scarce and a causal relationship is
      questionable. This study explored the prospective association between alexithymia
      and cardiovascular events in middle-aged participants without cardiovascular
      history at baseline. METHODS: The 26-item Toronto Alexithymia Scale (TAS-26) was
      completed by 5586 participants of the French SUpplementation en VItamines et
      Mineraux AntioXydants cohort (41.4% of men, M [SD] age = 52.2 [6.3] years) in
      1996-1997. Covariates measured at baseline included age, occupational status,
      depressive symptoms, smoking status, body mass index, hypertension, diabetes,
      hypercholesterolemia, and hypertriglyceridemia. The follow-up ran from January 1,
      1998, to the date of the first cardiovascular event, the date of death or
      September 1, 2007, whichever occurred first. Cardiovascular events were validated
      by an independent expert committee. Hazard ratios and 95% confidence intervals
      were computed with Cox regressions. RESULTS: During an average of 8.9 years of
      follow-up, 171 first cardiovascular events were validated. After adjustment for
      age, sex, and occupational status, there was no association between baseline
      alexithymia and cardiovascular events at follow-up (hazard ratio [95% confidence
      interval] for 15 points of TAS-26 = 1.00 [0.81-1.23], p > .99). Adjusting for all
      covariates, using binary TAS-26 cut-offs or TAS-26 subscores yielded similar
      nonsignificant results. CONCLUSIONS: In this large prospective study, alexithymia
      and cardiovascular events were not associated among a nonclinical population.
      This casts some doubt on whether alexithymia could be a meaningful target in the
      prevention of cardiovascular diseases. CLINICAL TRIAL REGISTRATION:
      Clinicaltrials.gov (NCT00272428).

PMID- 29649037
TI  - Immunotherapy in head and neck cancer: a new paradigm.

PMID- 29649038
TI  - The effect and mechanism of millepachine-disrupted spindle assembly in tumor
      cells.
AB  - Millepachine (MIL) is a bioactive natural product that shows great potential for
      cancer treatment. Previous studies showed that MIL was a novel cancer drug
      candidate with a special structure. To provide reference for the research and
      development of MIL, we further investigated the mechanism of MIL inducing G2/M
      arrest and found MIL disrupted spindle assembly in tumor cells. In this study, we
      investigated the disrupting spindle assembly effects of MIL with a focus on its
      potential mechanism of action. First, we indicated that MIL did not inhibit
      microtubule polymerization from the results of in-vivo microtubule nucleation
      assay and microtubule polymerization in-vitro assay but delayed this process by
      inhibiting the production of ATP in tumor cells. Thereafter, we investigated the
      effect of MIL on the mitotic spindle. We found that MIL induced multipolar
      spindles by inhibiting the activity of Eg5 and inhibited mitotic spindle
      formation and chromatin condensation by the activation of the spindle assembly
      checkpoint (SAC) in tumor cells. These results established a novel function of
      MIL in regulating the assembly of mitotic spindle. As Eg5 and SAC are antitumor
      targets, effect of MIL on the Eg5 protein and SAC activation hinted that MIL has
      novel application in the development of antitumor drugs.

PMID- 29649039
TI  - Barriers to Rehabilitation Care in Pediatric Cochlear Implant Recipients.
AB  - OBJECTIVE: The purpose of this study was to assess barriers to rehabilitation
      care for pediatric cochlear implant (CI) recipients. STUDY DESIGN: Cross
      sectional questionnaire study. SETTING: Tertiary medical center. PATIENTS:
      Parents of children who received a CI from October 1996 to June 2013. MAIN
      OUTCOME MEASURE(S): Factors related to access to and barriers in audiology and
      speech therapy services, factors related to CI use, and performance with CI using
      the Parents' Evaluation of Aural/Oral Performance of Children (PEACH). RESULTS:
      Thirty-five parents participated in the study (21 rural residents and 14 urban
      residents). Distance was a significant barrier to audiology services for rural
      participants compared with urban participants (p = 0.01). Consistent CI use was
      complicated by mechanical complications or malfunction in 70% of rural children
      compared with 33% of urban children (p = 0.05). Only 10% of rural children were
      able to access speech therapy services at diagnosis compared with 42% of urban
      children (p = 0.04). Low socioeconomic (SES) status and Medicaid insurance were
      associated with a lack of local speech therapists and medical/mechanical CI
      complications. Higher parental educational attainment was associated with higher
      PEACH scores in quiet conditions compared with families with lower parental
      education (p = 0.04). CONCLUSIONS: Rural children are often delayed in receipt of
      CI rehabilitation services. Multiple barriers including low SES, insurance type,
      and parental education can affect utilization of these services and may impact
      the recipient language development. Close follow-up and efforts to expand access
      to care are needed to maximize CI benefit.

PMID- 29649040
TI  - Improvement in Patient-reported Hearing After Treatment With Bevacizumab in
      People With Neurofibromatosis Type 2.
AB  - OBJECTIVE: Assess patient-reported outcomes (PRO) for hearing and tinnitus
      relative to clinical hearing assessment in people with neurofibromatosis 2 (NF2)
      associated hearing loss. STUDY DESIGN: Prospective, open label, phase-II clinical
      trial with PRO administered pre-, post-, and after treatment. SETTING: Three
      tertiary referral centers. PATIENTS: Fourteen patients with NF2, median age of 30
      years (range, 14-79 yr) and progressive hearing loss (median baseline word
      recognition score, 60%; range, 13-82%). Half of these patients achieved objective
      hearing response (word recognition score improved beyond the 95% critical
      difference versus baseline). INTERVENTION: Bevacizumab 7.5 mg/kg was administered
      every 3 weeks for 48 weeks, followed by surveillance for 24 weeks off-drug. MAIN
      OUTCOME MEASURES: Speech, spatial, and qualities of hearing scale (SSQ) and
      tinnitus reaction questionnaire (TRQ) to assess hearing difficulties in life
      situations and tinnitus related distress. RESULTS: Patient-reported speech
      understanding and auditory quality improved with bevacizumab treatment and were
      significantly correlated with word recognition scores, but not pure tone
      threshold average. There was no change in spatial perception after treatment.
      Reduction in tinnitus distress after treatment with bevacizumab did not reach
      statistical significance. CONCLUSION: Participants had reductions in hearing
      difficulty during treatment with bevacizumab, suggesting that patients
      subjectively experience hearing-related benefit mirroring clinical hearing
      assessments. We suspect the lack of significant reduction in tinnitus distress is
      related to small sample size and low intensity of distress in our sample. These
      data highlight the usefulness of PRO measures to assess benefits of treatment in
      the setting of NF2-associated hearing loss.

PMID- 29649041
TI  - Squamous Papilloma of the External Auditory Canal.

PMID- 29649042
TI  - Factors Associated With the Benefits of Concurrent Administration of
      Intratympanic Steroid Injection With Oral Steroids in Patients With Acute
      Acoustic Trauma.
AB  - OBJECTIVE: To analyze the factors associated with the benefits of concurrent
      administration of intratympanic steroid injection (ITSI) and oral steroids in
      patients with acute acoustic trauma (AAT) incurred during military training.
      STUDY DESIGN: Retrospective analysis. PATIENTS: Nineteen patients eligible under
      the criteria established concerning treatment for AAT were retrospectively
      reviewed in this study. INTERVENTIONS: ITSI treatments were administered
      simultaneously alongside oral prednisolone. MAIN OUTCOME MEASURES: Patients were
      categorized into two groups depending on the time elapsed between exposure to the
      noise and treatment initiation: 1) "Early Treatment initiation," defined as the
      treatment being initiated between 3 and 7 days; and 2) "Delayed treatment
      initiation," defined as the treatment being initiated in >7 days. Pure-tone air
      conduction threshold audiometry, to record the pure-tone average (PTA) at 2, 4,
      and 8 kHz, was conducted upon each patient's initial visit, and 1 month after
      starting treatment. The degree of hearing gain (hearing gain [dB] = [initial PTA]
      - [final PTA]) was calculated and used as the metric for determining the
      treatment's outcome. The initial PTA and treatment onset were adopted as possible
      associated factors. RESULTS: The mean ages of each group were 22.00 +/- 2.12
      years and 22.83 +/- 2.64 years, respectively (p = 0.28). The initial PTAs were
      46.41 +/- 12.73 dB and 47.22 +/- 14.74 dB, respectively (p = 1.00).In the
      multivariable linear regression analysis, the initial PTA and the treatment
      initiation showed a significant association (R = 0.37). The unstandardized
      regression coefficient of the initial PTA was 0.37 (p = 0.04). Patients with
      early treatment initiation showed significant improvement in the degree of
      hearing gain compared with delayed treatment initiation (unstandardized
      regression coefficient = 12.63, p = 0.01). CONCLUSIONS: We demonstrated the
      importance of early treatment onset for maximizing the benefits of concurrent
      administration of ITSI with oral steroids in patients with AAT suffered during
      military training. Further evaluation is needed to confirm the factors associated
      with the efficacy of concurrent ITSI with oral steroids.

PMID- 29649043
TI  - Permeation Enhancers for Intratympanically-applied Drugs Studied Using
      Fluorescent Dexamethasone as a Marker.
AB  - HYPOTHESIS: Entry of locally applied drugs into the inner ear can be enhanced by
      chemical manipulations. BACKGROUND: Perilymph drug concentrations achieved by
      intratympanic applications are well below the applied concentration due to
      limited entry through the round window (RW) membrane and stapes. Chemical
      manipulations to increase entry permeability could increase the effectiveness of
      drug therapy with local applications. METHODS: Dexamethasone-fluorescein (F-dex)
      was used as an entry marker. F-dex was applied to the RW niche of guinea pigs as
      a 20 MUL bolus of 1 mM solution. After a 1 hour application, 10 samples of
      perilymph were collected sequentially from the lateral semicircular canal,
      allowing F-dex distribution throughout the perilymph to be quantified. Entry was
      also measured with the applied solution additionally containing dimethyl
      sulfoxide (DMSO), N-methylpyrrolidone (NMP), saponin, caprate, benzyl alcohol
      (BA) or poloxamer 407 (P407). Combinations of saponin or BA with P407 were also
      compared. RESULTS: In control experiments, F-dex entered the inner ear slowly at
      both the RW and stapes. The total F-dex recovered in all 10 samples from each
      animal averaged 2.1 pMoles for controls, 1.71 pMoles for 17% P407, 3.70 pMoles
      for caprate, 8.04 pMoles for DMSO, 16.32 pMoles for NMP, 31.0 pMoles for saponin,
      and 67.3 pMoles for 4% BA. Entry with DMSO, NMP, saponin and 4% BA were all
      significantly higher than the controls (one-way ANOVA). CONCLUSION: These studies
      confirm that entry of drugs into the ear can be markedly enhanced with the use of
      chemical permeation-enhancing agents.

PMID- 29649044
TI  - Oval Window Size and Shape: a Micro-CT Anatomical Study With Considerations for
      Stapes Surgery.
AB  - BACKGROUND: The oval window is an important structure with regard to stapes
      surgeries, including stapedotomy for the treatment of otosclerosis. Recent study
      of perioperative imaging of the oval window has revealed that oval window niche
      height can indicate both operative difficulty and subjective discomfort during
      otosclerosis surgery. With regard to shape, structures incorporated into the oval
      window niche, such as cartilage grafts, must be compatible with the shape of the
      oval window. Despite the clinical importance of the oval window, there is little
      information regarding its size and shape. METHODS: This study assessed oval
      window size and shape via micro-computed tomography paired with modern
      morphometric methodology in the fetal, infant, child, and adult populations.
      Additionally, the study compared oval window size and shape between sexes and
      between left- and right-sided ears. RESULTS: No significant differences were
      found among traditional morphometric parameters among age groups, sides, or
      sexes. However, geometric morphometric methods revealed shape differences between
      age groups. Further, geometric morphometric methods provided the average oval
      window shape and most-likely shape variance. CONCLUSION: Beyond demonstrating
      oval window size and shape variation, the results of this report will aid in
      identifying patients among whom anatomical variation may contribute to surgical
      difficulty and surgeon discomfort, or otherwise warrant preoperative adaptations
      for the incorporation of materials into and around the oval window.

PMID- 29649045
TI  - Clinical Usefulness of 18F-FDG PET/CT for Staging Cancer of the External Auditory
      Canal.
AB  - OBJECTIVE: Our objective was to evaluate the clinical usefulness of positron
      emission tomography/computed tomography using 2-deoxy-2-[F-18]fluoro-D-glucose
      (FDG-PET/CT) for staging cancer of the external auditory canal (EAC). STUDY
      DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS:
      Twenty-three patients (seven men, 16 women, mean age of 59.6-year-old) who
      underwent FDG-PET/CT and high-resolution CT within 1 month for staging cancer of
      the EAC between July 2006 and December 2014 were enrolled in this study.
      INTERVENTION: FDG-PET/CT, high-resolution CT. MAIN OUTCOME MEASURES: Sensitivity,
      specificity, and accuracy for diagnosing nodal metastases. RESULTS: Most primary
      tumors were FDG-avid and maximum standardized uptake values were 7.72 +/- 3.04
      and 9.06 +/- 3.94 for the early (60 min) and delayed (120 min) phases of FDG
      PET/CT, respectively. FDG-PET/CT was capable of detecting small nodal metastases
      (short axis <10 mm), and patient-based sensitivity, specificity, and accuracy of
      FDG-PET/CT for the N staging were 71.4, 81.3, and 78.3%, respectively. There were
      no patients with distant metastases in our cohort. Compared with the combination
      of clinical examination and conventional imaging methods, additional FDG-PET/CT
      resulted in a change in the surgical strategy in five patients (21.7%).
      CONCLUSIONS: Most primary cancers of the EAC are FDG-avid, and FDG-PET/CT is
      useful for detecting small nodal metastases, followed by the change in the
      surgical strategy.

PMID- 29649046
TI  - Range of Peak Head Velocity in Video Head Impulse Testing for Pediatric Patients.
AB  - OBJECTIVE: To examine peak head velocity in video head impulse testing of
      pediatric patients and its effect on vestibulo-ocular reflex (VOR) gain. STUDY
      DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS:
      Pediatric patients ages 3 to 18 years old who underwent video head impulse
      testing during clinical evaluation of dizziness and/or imbalance.
      INTERVENTION(S): Conducted video head impulse test (vHIT) in horizontal, left
      anterior-right posterior (LARP), and right anterior-left posterior (RALP) planes.
      MAIN OUTCOME MEASURE(S): Peak head velocity and mean VOR gain for individual
      semicircular canals in different age groups. RESULTS: For the horizontal plane,
      vHIT peak head velocity greater than 150 degrees/s was achieved in 43 to 63% of
      219 patients. In contrast, vHIT peak head velocity greater than 150 degrees/s was
      achieved in only 3 to 14% for the LARP and RALP planes. Analyses of differences
      in mean VOR gains among three ranges of peak head velocity (100-125 degrees/s,
      126-150 degrees/s, and >150 degrees/s) by paired-t tests were not significant (p
      > 0.05) within individual patients. Mean VOR gains of three vertical canals in
      younger patients were significantly lower with higher peak head velocities
      compared with older children (p < 0.05). CONCLUSIONS: Peak head velocities of
      greater than 150 degrees/s may not be feasible in a large proportion of children
      and adolescents, especially in LARP and RALP planes. However, such high
      velocities may not be necessary in the pediatric population since VOR gain values
      obtained at lower peak head velocities of 100 to 150 degrees/s were found to be
      comparable to those observed at higher velocities.

PMID- 29649047
TI  - Preliminary Outcomes Report for CO2 Laser Assisted Electric-Acoustic Cochlear
      Implantation.
AB  - OBJECTIVE: Report on the safety/efficacy of a novel, carbon dioxide (CO2) laser
      assisted protocol for hearing-preservation cochlear implantation (HPCI) and
      electric-acoustic stimulation (EAS). STUDY DESIGN: Retrospective case review.
      SETTING: Tertiary referral center. PATIENTS: Adult patients meeting established
      criteria for HPCI and EAS. INTERVENTION: Therapeutic/rehabilitative. A
      standardized protocol used CO2 laser to achieve meticulous hemostasis and perform
      cochleostomy was evaluated. MAIN OUTCOME MEASURES: Audiometric assessments
      included low-tone pure tone average (LtPTA), consonant-nucleus-consonant (CNC),
      and AzBio scores. Primary outcomes were low-tone hearing-preservation (LtHP) and
      EAS usage rates. Secondary outcomes included change in LtPTA, outcomes
      durability, and the rate/onset/presentation of delayed hearing loss (DHL). Subset
      analyses stratified data by presenting LtPTA and surgeon experience. RESULTS:
      Forty-seven patients and 52 ears were included. Mean follow-up was 20.7 +/- 12.6
      months. When adjusted for preoperative LtPTA less than 60 dB, the LtHP rate was
      77%. This was significantly better than for patients with LtPTA more than 60 dB
      (24%; p < 0.0001). Outcomes were highly durable. EAS usage was excellent in those
      with LtPTA less than 60 dB (100%). Nine patients developed DHL. Three additional
      patients (25%) were successfully salvaged via steroids. Both CNC and AzBio scores
      improved significantly (p < 0.0001) at definitive testing. Speech-hearing scores
      did not differ significantly between patients using/not using EAS. The
      complication rate was 3.8%; none were caused by the laser. Surgeon experience was
      associated with significantly better outcomes. CONCLUSION: Use of a CO2 laser
      assisted HPCI protocol was safe and effective. Outcomes were consistent with
      contemporary literature reporting. Patient selection and surgeon experience both
      significantly impacted outcomes.

PMID- 29649048
TI  - Improved Speech Perception in Cochlear Implant Users With Interleaved High-Rate
      Pulse Trains.
AB  - OBJECTIVE: Electrical stimulation with a cochlear implant (CI) elicits abnormally
      high neural synchrony, which poses significant challenges for speech perception.
      Previous investigations showed that constant-amplitude high-rate pulse trains
      (HRPs) desynchronize neural responses and improve stimulus encoding. The study
      objective was to investigate the effects of HRP on speech perception in adult CI
      users. STUDY DESIGN: Prospective, within-subject design. SETTING: Tertiary CI
      center. PATIENTS: Ten adult CI recipients. INTERVENTION: Sentence stimuli were
      created by modifying a basic continuous interleaved sampling (CIS) strategy
      (1,000 pulses per second; pps) with interleaved biphasic pulse trains (3,000 pps)
      on even electrodes. Institute of Electrical and Electronics Engineers sentences
      in quiet and in noise were tested without HRP, and with HRPs of various
      stimulation levels. MAIN OUTCOME MEASURE: Sentence perception in percent correct
      was calculated for all conditions. The highest speech perception score with HRP
      stimulation was defined as "max-HRP." RESULTS: Group analyses showed
      significantly improved sentence perception in background noise with HRPs (p <
      0.001). There was no significant difference for sentence perception in quiet for
      the group. However, seven of 10 subjects experienced some benefit from HRP
      stimuli in quiet and the degree of HRP benefit showed significant relationships
      with baseline performance and age at implantation, indicating that HRP stimuli
      may be most beneficial for older patients or poorer performers. CONCLUSIONS:
      Significant improvement in speech perception in noise was observed with HRP
      stimuli. Some recipients may also benefit from HRP stimulation in quiet.
      Interleaved HRPs hold promise as a novel stimulation paradigm with clinical sound
      processing strategies to improve patient performance.

PMID- 29649049
TI  - A Comparison of Repeatability and Usability of Semi-Automated Volume Segmentation
      Tools for Measurement of Vestibular Schwannomas.
AB  - OBJECTIVE: Semi-automated volume segmentation tools (SAVST) offer a less time
      consuming technique compared with manual volume segmentation method. No data
      exists to suggest which of the available applications are optimal for use with
      vestibular schwannomas (VS). This study aims to compare repeatability and
      usability of three different SAVST for measurement of VS. STUDY DESIGN:
      Experimental comparison of three SAVST. SETTING: Tertiary skull base unit.
      PATIENTS: Twenty-four patients with a unilateral VS imaged with T1-weighted
      Gadolinium enhanced MRI. INTERVENTION: Repeated measurements made to determine
      intra and inter-observer agreement. This was repeated using three different
      SAVST. MAIN OUTCOME MEASURES: 1) Intra- and inter-observer intraclass correlation
      coefficients (ICC), repeatability coefficients (RC), and relative smallest
      detectable differences (%SDD).2) Usability as determined by the mean number of
      steps and time required per tumor measurement and the proportion of cases where
      manual editing was required. RESULTS: Intra-observer ICCs were significantly
      better for SliceOmatic and OleaSphere than AW VolumeShare (0.998 versus 0.994, p
      < 0.05). Inter-observer ICCs were also better for SliceOmatic (0.994) and
      OleaSphere (0.989) compared with AW VolumeShare (0.976), however, this was only
      significant for SliceOmatic (p = 0.012). SliceOmatic had a poorer usability
      profile requiring more manual editing, time, and individual steps per measurement
      but its "watershed segmentation" algorithm was better at measuring cystic or
      heterogenous tumors. CONCLUSIONS: This is the first study to compare three SAVST
      for measurement of VS. While SliceOmatic had the highest repeatability, Olea
      Sphere combined comparable repeatability with improved usability and a greater
      degree of automation and was, therefore, deemed optimal for use in routine
      clinical practice.

PMID- 29649050
TI  - Temporal Bone Histopathology in Cockayne Syndrome.
AB  - : Cockayne syndrome (CS) is a rare autosomal recessive syndrome resulting in
      defective DNA repair. Its features include cachectic dwarfism, hearing loss, skin
      hypersensitivity to sunlight, premature aging, and dementia. Presented is a right
      temporal bone of a patient who died at the age of 29 years. The clinical course
      was compatible with type 1 CS, the classical form. Homozygous missense variant in
      the ERCC6 gene (Excision Repair Cross-Complementation group 6) was found,
      compatible with CS complementation group B. Five years before his death he
      complained of tinnitus. An audiogram 3 and a 1/2 years before his death
      demonstrated a moderate symmetrical sensorineural hearing loss at 2 to 8 kHz. The
      speech reception threshold was 20 dB, and the word recognition score was 100% on
      the right.Histopathology revealed a near normal population of inner hair cells
      except in the basal 5 mm of the cochlea, and mild loss of outer hair cells
      particularly at the base of the cochlea. Severe atrophy of the spiral ligament
      and atrophy of stria vascularis and spiral prominence was present. There was loss
      of Claudius cells, outer sulcus cells, and mesenchymal cells on the scala tympani
      side of the basilar membrane and loss of cellularity of the limbus. There was a
      moderate loss of Scarpa's and spiral ganglion neurons, with the most severe loss
      in the basal segment. The vestibular neuro-epithelium was nearly intact, with the
      exception of mild loss in the saccule. The vestibular perilymphatic, and to a
      lesser extent endolymphatic spaces, were filled with filamentous material and
      osteoid. The patient had better hearing and a larger complement of neurons
      compared with the few published case reports.Neurodegenerative symptoms are
      likely attributed to the effect of intramitochondrial reactive oxygen species.
      The pathogenesis of hearing loss in CS may shed light on other causes of hearing
      loss, such as that induced by noise.

PMID- 29649051
TI  - Comparison of Video Head Impulse Test (vHIT) Gains Between Two Commercially
      Available Devices and by Different Gain Analytical Methods.
AB  - OBJECTIVES: To evaluate whether video head impulse test (vHIT) gains are
      dependent on the measuring device and method of analysis. STUDY DESIGN:
      Prospective study. METHODS: vHIT was performed in 25 healthy subjects using two
      devices simultaneously. vHIT gains were compared between these instruments and
      using five different methods of comparing position and velocity gains during head
      movement intervals. RESULTS: The two devices produced different vHIT gain results
      with the same method of analysis. There were also significant differences in the
      vHIT gains measured using different analytical methods. The gain analytic method
      that compares the areas under the velocity curve (AUC) of the head and eye
      movements during head movements showed lower vHIT gains than a method that
      compared the peak velocities of the head and eye movements. The former method
      produced the vHIT gain with the smallest standard deviation among the five
      procedures tested in this study. CONCLUSION: vHIT gains differ in normal subjects
      depending on the device and method of analysis used, suggesting that it is
      advisable for each device to have its own normal values. Gain calculations that
      compare the AUC of the head and eye movements during the head movements show the
      smallest variance.

PMID- 29649052
TI  - Recurrence in Benign Paroxysmal Positional Vertigo: A Large, Single-Institution
      Study.
AB  - OBJECTIVE: To report rates of recurrence in benign paroxysmal positional vertigo
      (BPPV) and associated patient and disease factors. STUDY DESIGN: Retrospective
      chart review. SETTING: Single high-volume otology practice. PATIENTS: Patients
      diagnosed with BPPV from 2007 to 2016 with documented resolution of symptoms.
      INTERVENTION: Diagnostic and particle repositioning maneuvers for BPPV. MAIN
      OUTCOME MEASURES: BPPV recurrence, time to recurrence, and ear(s) affected at
      recurrence. RESULTS: A total of 1,105 patients meeting criteria were identified.
      Of this population, 37% had recurrence of BPPV in either ear or both ears.
      Overall same-ear recurrence rate was 28%; 76% of recurrences involved the same
      ear(s) as initial presentation. Recurrences that occurred after longer disease
      free intervals were more likely to involve the opposite ear than early
      recurrences (p = 0.02). Female sex (40.4% versus 32.7%, p = 0.01) and history of
      previous BPPV (57.5% versus 32.4%, p < 0.0005) were associated with increased
      risk of recurrence, while history of Meniere's disease, diabetes mellitus, and
      traumatic etiology were not. Approximately, half (56%) of recurrences occurred
      within 1 year of resolution. CONCLUSIONS: A large single-institution study of
      recurrence in BPPV is presented along with Kaplan-Meier disease-free survival
      curves. Female sex and history of previous BPPV were associated with increased
      recurrence, while previously suspected risk factors for recurrence including
      history of Meniere's disease, diabetes, and trauma were not. Remote recurrence is
      more likely to involve the contralateral ear than early recurrence. These data
      solidify the expected course of treated BPPV allowing for improved clinical care
      and patient counseling.

PMID- 29649053
TI  - Bilateral Congenital Cholesteatoma.
AB  - OBJECTIVE: To report the first large case series of extremely rare bilateral
      congenital cholesteatoma (CC). STUDY DESIGN: A retrospective cohort study.
      SETTING: University hospital otology referral clinic. PATIENTS: Six hundred four
      children with surgically confirmed CC. MAIN OUTCOME MEASURES: The bilateral CCs
      were compared with the unilateral CCs. RESULTS: The incidence of bilateral CC was
      3.6% (22/615) per case or 1.8% (11/604) per child. Bilateral CC did not differ
      from unilateral CC regarding its demographics, and invasiveness by the proportion
      of advanced CC as 31.8% (7/22) versus 28.2% (167/594). But the invasiveness or
      location randomly differed between the ears, that advanced CC per child was
      higher as 45.4% (5/11). Bilateral exploration was attempted with a concern for
      hearing loss, which featured a combination of laser myringotomy to treat early CC
      and endaural laser-assisted single-stage inside-out cholesteatoma surgery to
      treat advanced CC. Bilateral exploration was difficult in three children with
      initially negative otoendoscopy. Among the seven advanced CC, proportion of
      anterior type was 71.4% (5/7), who all exhibited more than 20 dB HL, but two
      posterior type retained normal hearing. Therefore, bilateral advanced CCs of
      anterior origin showed poorest hearing outcome as bilateral more than 20 dB HL,
      which were in two children. Six second-look operations and one third-look
      operation were required to treat six residual CCs (30%) in four children (40%),
      including bilateral residual CC in two (20%); such reoperations were
      significantly more frequent than in unilateral CC. CONCLUSION: The diagnosis of
      bilateral CC required high index of suspicion from TBCT, and early bilateral
      exploration.

PMID- 29649054
TI  - The effect of a single textured insole in gait rehabilitation of individuals with
      stroke.
AB  - Rehabilitation interventions designed to restore gait symmetry in individuals
      with stroke are not always effective. The goal was to evaluate the long-term
      effect of using a single textured insole in gait rehabilitation. Ten individuals
      with stroke who showed asymmetrical stance were randomly divided into two groups
      and participated in physical therapy. Individuals in the experimental group
      received a 6-week physical therapy while being provided with a textured insole in
      the shoe on the unaffected side. Individuals in the control group received a 6
      week physical therapy only. Both groups underwent a battery of identical tests
      before the start of the rehabilitation intervention, following its completion,
      and 4 months after the end of therapy. After the intervention, weight bearing
      (WB) on the affected side and gait velocity increased in the experimental group
      (P<0.05) to a larger degree compared with the control group. Moreover, symmetry
      of gait was increased in the experimental group (P<0.05). Improvements in WB,
      gait velocity, and symmetry of gait were maintained in the experimental group
      after the end of 4-month retention period. The study outcome revealed that a 6
      week intervention involving a single textured insole could result in a long
      lasting improvement of gait velocity, symmetry of WB, and gait in individuals
      with stroke.

PMID- 29649055
TI  - The Impact of Once- versus Twice-Daily Enoxaparin Prophylaxis on Risk for Venous
      Thromboembolism and Clinically Relevant Bleeding.
AB  - BACKGROUND: Venous thromboembolism is a life- or limb-threatening complication
      that occurs in plastic surgery patients. At present, the optimal dose of
      enoxaparin that balances the risk of venous thromboembolism and the risk of
      medication-related adverse drug events-specifically, bleeding-remains unknown.
      METHODS: This study compared pharmacodynamic and clinical outcomes, including 90
      day venous thromboembolism and 90-day clinically relevant bleeding, between two
      prospectively performed clinical trials whose sole difference was postoperative
      anticoagulation strategy. Patients in trial 1 received enoxaparin 40 mg once
      daily for the duration of inpatient stay, and patients in trial 2 received
      enoxaparin 40 mg twice daily for the duration of inpatient stay. The study also
      examined the potential impact of a weight-based twice-daily prophylaxis strategy
      to achieve in-range anti-factor Xa levels. RESULTS: The study compared 94
      patients who received once-daily enoxaparin to 118 patients who received twice
      daily enoxaparin. Twice-daily enoxaparin was associated with a significant
      decrease in 90-day acute venous thromboembolism (0 percent versus 5.3 percent; p
      = 0.012) and a nonsignificant increase in 90-day clinically relevant bleeding
      (6.8 percent versus 3.2 percent; p = 0.25). Twice-daily enoxaparin at 0.4 to 0.5
      mg/kg may allow an increased proportion of patients to avoid both inadequate
      anticoagulation and overanticoagulation, based on anti-factor Xa levels.
      CONCLUSIONS: Twice-daily enoxaparin is superior to once-daily enoxaparin for 90
      day acute venous thromboembolism risk reduction. Twice-daily enoxaparin may
      increase clinically relevant bleeding, although observed differences in this
      study were not significant. Weight-based twice-daily enoxaparin dosing may
      optimize the risks and benefits of prophylactic anticoagulation after plastic and
      reconstructive surgery. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

PMID- 29649056
TI  - Topical Aloe Vera Gel for Accelerated Wound Healing of Split-Thickness Skin Graft
      Donor Sites: A Double-Blind, Randomized, Controlled Trial and Systematic Review.
AB  - BACKGROUND: Aloe vera has been used to treat wounds since ancient times. However,
      data regarding the efficacy of aloe vera for burns and split-thickness skin graft
      donor sites are inconclusive. METHODS: A double-blind, randomized, controlled
      trial was conducted. Patients who underwent split-thickness skin graft harvesting
      from the thigh were included. Split-thickness skin graft donor sites were divided
      into two groups: the aloe vera group and the placebo group. The visual analogue
      scale score was used to evaluate pain, and complete epithelialization was
      assessed. The authors searched electronic databases and included only
      international clinical trials published in the English language. RESULTS: Twelve
      patients with 24 donor sites participated. Times to complete epithelization for
      the aloe vera and placebo groups were 11.5 +/- 1.45 and 13.67 +/- 1.61 days,
      respectively (p < 0.05). Visual analogue scale scores after wound dressing for
      the aloe vera and placebo groups were 17.18 +/- 13.17 and 18.63 +/- 11.20,
      respectively. No statistical significance was found between groups. Five articles
      met the inclusion criteria: four involved burns and one involved split-thickness
      skin graft donor sites. Three studies of burn wounds demonstrated improved
      epithelization and one did not. The split-thickness skin graft donor-site study
      indicated that wound healing time for the control group was significantly
      different from that of the aloe vera and placebo groups. The healing rate was not
      statistically different between groups. CONCLUSION: Topical aloe vera gel
      significantly demonstrated accelerated split-thickness skin graft donor-site
      healing but did not show significant pain relief. CLINICAL QUESTION/LEVEL OF
      EVIDENCE: Therapeutic, I.

PMID- 29649057
TI  - Eliminating Geographic Bias Improves Match Results: An Analysis of Program
      Preferences and Their Impact on Rank Lists and Results.
AB  - BACKGROUND: Previous studies have demonstrated that programs emphasize United
      States Medical Licensing Examination scores, publications, and geography in
      creating rank lists. The authors aimed to quantify the importance of geography
      and to determine how eliminating geographic preferences would affect Match
      outcomes. METHODS: The Match algorithm was implemented and validated on 6 years
      of deidentified data from the San Francisco Match (2009 to 2014). A "consensus"
      ranking was generated for each year-all applicants were ordered into a single
      list using Markov chain rank aggregation. Each program's rank list was reordered
      using the consensus list, and a new Match result was simulated. Statistical
      analysis was carried out with Microsoft Excel. RESULTS: Variation of program rank
      lists from the consensus rank list was driven by geography (training in the same
      medical center or state as the ranking program), "pedigree" (top 25 ranking of
      applicants' prior training), and foreign medical graduation status. Step 1
      scores, publications, and medical school or residency region were not factors.
      The simulated Match resulted in a slight increase in the match rate. The median
      normalized number needed to match decreased from 6.7 to 6.5, and 80 percent of
      applicants had an unchanged or better result compared to the actual Match.
      CONCLUSIONS: Geography is the primary driver of variation between program rank
      lists. Removing this variation would result in fewer unfilled positions, no
      significant change in the average number needed to match, and improved Match
      outcomes for most applicants. Programs should critically evaluate whether their
      geographic biases reflect underlying information about applicant quality.

PMID- 29649058
TI  - Asymptomatic Deep Vein Thrombosis during Free Flap: Concerns in Free Flap
      Surgery.
AB  - BACKGROUND: Venous insufficiency is the most frequent cause of failure in free
      flap reconstruction of the lower extremity. When deep vein thrombosis is detected
      during preoperative assessment of the lower extremity, decisions regarding
      treatment plans become difficult, and no relevant guidelines regarding surgery
      and preoperative treatment of patients with deep vein thrombosis who need a free
      flap transfer are currently available. METHODS: To find a relevant guideline in
      decision-making regarding surgery and preoperative treatment of patients with
      deep vein thrombosis who require free flap reconstruction, a systematic
      literature review was conducted searching MEDLINE, PubMed Central, Cochrane, and
      Embase databases for articles published between 1996 and 2015. In addition, the
      authors introduced six of their cases of deep vein thrombosis diagnosed before
      free flap surgery in which the flap survived. RESULTS: The literature review
      identified two articles that discussed intraoperative deep vein thrombosis
      diagnosed in three patients, including the reported cases. Analyses included
      epidemiology, cause, and management strategy. A consensus for the management of
      asymptomatic deep vein thrombosis before free flap surgery is still lacking. In
      the authors' cases, successful flap transfer was possible by proceeding with an
      appropriate preoperative evaluation, intensive anticoagulation treatment,
      intraoperative reperfusion procedure, and postoperative care. CONCLUSION:
      Preoperatively detected asymptomatic deep vein thrombosis is not a
      contraindication for free flap reconstruction, and a flap transfer can be
      successfully performed with suitable planning and management. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

PMID- 29649059
TI  - Enhancement of Progenitor Cells by Two-Step Centrifugation of Emulsified
      Lipoaspirates.
AB  - BACKGROUND: Adipose-derived stem cells, endothelial progenitor cells, and soluble
      factors jointly contribute to the regenerative effect of fat grafts. Nanofat
      grafting emulsifies the lipoaspirate and increases the progenitor cell yield. In
      the present study, the authors evaluated their extended nanofat grafting method
      that includes two additional centrifugation steps and results in a lipoaspirate
      of low volume that they termed "lipoconcentrate." Furthermore, the authors
      investigated the oily fractions after centrifugation for their regenerative
      potential. METHODS: Lipoaspirates of 20 healthy patients were processed by
      emulsification and/or centrifugation. Six groups were created: native (not
      emulsified) fat, 1* centrifuged native fat, 2* centrifuged native fat, nanofat
      (emulsified), 1* centrifuged nanofat, and lipoconcentrate (i.e., 2* centrifuged
      nanofat). The oily phases after the centrifugation steps were collected.
      Progenitor cells and basic fibroblast growth factor, insulin-like growth factor
      1, matrix metalloproteinase-9, platelet-derived growth factor-BB, and vascular
      endothelial growth factor-A levels were measured by flow cytometry and
      immunoassays. RESULTS: Lipoconcentrate contained significantly higher numbers of
      adipose-derived stem cells and endothelial progenitor cells per gram compared
      with all other fractions. No difference of all five soluble factors between
      groups was found. The oily phases after centrifugation showed no or very few
      adipose-derived stem cells and endothelial progenitor cells, and no or very low
      levels of soluble factors. CONCLUSIONS: Centrifugation of emulsified
      lipoaspirates increases the progenitor cell count in the lipoaspirate. The oily
      phase after centrifugation of lipoaspirates may be disposable because of the
      minuscule content of progenitor cells and soluble factors.

PMID- 29649060
TI  - Liposuction Aspirate Fluid Adipose-Derived Stem Cell Injection and Secondary
      Healing in Fingertip Injury: A Pilot Study.
AB  - BACKGROUND: Although fingertip injuries account for a high proportion of trauma
      patients, the correct surgical approach is still debated. The authors compared
      the traditional conservative approach and a new treatment based on the injection
      of liposuction aspirate fluid. METHODS: Forty consecutive patients with a
      fingertip injury were dichotomized into group A (control group; conservative
      approach) and group B (treatment group). Group B underwent liposuction, followed
      by filtration of the lipoaspirate in a closed device (MyStem EVO kit), allowing
      the nonenzymatic separation of liposuction aspirate fluid, which was then
      injected at the site of injury. Objective outcomes were time for healing,
      strength, mobility of joint, and touch and sensory function. Subjective outcomes
      were cold intolerance, pain, hand disability, and aesthetic result. An aliquot of
      liposuction aspirate fluid was sent to the laboratory for cellular isolation and
      analysis by flow cytometry and in vitro differentiation assays. RESULTS: The
      average healing time was 22.3 days in group B and 24.9 days in group A (p <
      0.05). Eighty-five percent of group B patients and 67 percent of group A patients
      scored normal to diminished superficial sensibility (p < 0.05). Group A had
      higher pain and cold intolerance scores (p < 0.05). Group B scored greater
      aesthetic and disabilities outcome results (p < 0.05). The cell isolation yield
      was 8.3 * 10(5)/ml, with a percentage of viable cells of 74.3 percent. Flow
      cytometry identified a mesenchymal immunophenotype, and in vitro osteogenic and
      adipogenic induction confirmed the bilinear potential of the isolated cells.
      CONCLUSION: This clinical study demonstrates for the first time the regenerative
      potential of liposuction aspirate fluid adipose-derived stem cells in a clinical
      application. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

PMID- 29649061
TI  - Anatomical Consideration for the Safe Elevation of the Deep Circumflex Iliac
      Artery in Flap Surgery.
AB  - BACKGROUND: Deep circumflex iliac artery osteocutaneous flap transfer has
      frequently been applied to large defects in the maxillary and mandible regions,
      but the use rate has decreased gradually because of the complicated anatomy of
      the deep circumflex iliac artery. This study investigated the comprehensive
      anatomy of the deep circumflex iliac artery in relation to flap surgery with the
      aim of providing navigational guidelines for safe deep circumflex iliac artery
      harvesting. METHODS: Sixty-two sides of the hemi-abdominal wall were dissected in
      fixed Korean cadavers. Several dimensions of the deep circumflex iliac artery and
      its positional relationships with surgical landmarks were measured, and the
      patterns of the arterial supply and anastomosis were identified. RESULTS: The
      mean distance between the anterior superior iliac spine and the lateral border of
      the femoral artery was 57.5 mm. The deep circumflex iliac artery generally
      originated almost at the same level as the inguinal ligament, and its highest
      level was 14.8 mm superior to that ligament. Emerging points of the ascending
      branch were observed both medial and lateral to the anterior superior iliac
      spine, but no transverse branch pierced the transversus abdominis muscle medial
      to the anterior superior iliac spine. CONCLUSIONS: The incision line for safe
      deep circumflex iliac artery harvesting was parallel and 2 cm superior to the
      inguinal ligament and 6 cm from the anterior superior iliac spine. This position
      of the safe incision line can be easily determined using the thumb. Sex
      differences in the incidence of the deep circumflex iliac artery originating
      above or below the inguinal ligament will be another useful guide for easily
      detecting the deep circumflex iliac artery.

PMID- 29649062
TI  - National Mortality Rates after Outpatient Cosmetic Surgery and Low Rates of
      Perioperative Deep Vein Thrombosis Screening and Prophylaxis.
AB  - BACKGROUND: Concerns have arisen over reports of deaths occurring after certain
      outpatient plastic surgery procedures. Here, the authors present a national
      analysis, reporting on deaths occurring after outpatient cosmetic surgical
      procedures and venous thromboembolism screening. METHODS: A retrospective
      analysis of the American Association for Accreditation of Ambulatory Surgical
      Facilities database was performed for the years 2012 to 2017. The authors
      retrieved data for all deaths occurring in association with cosmetic plastic
      surgery procedures. Patient demographics, procedural data, venous thromboembolism
      risk factor assessment, and cause of death were analyzed. Deidentified medical
      records, including coroner's reports, were reviewed where available. RESULTS:
      Data for 42 deaths were retrieved. Of these, 90.5 percent (n=38) were female, and
      61.9 percent were Caucasian (n=26). Mean age was 51.6 years, while mean body mass
      index was 29.5 kg/m(2). Overall, 54.8 percent of these deaths occurred after
      abdominoplasty: 42.9 percent in isolation, 9.5 percent in combination with breast
      surgery, and 2.4 percent with facial surgery. Of the causes of death, most (38.1
      percent) were thromboembolic in origin. Notably, in 25 of 42 cases, venous
      thromboembolism risk factor assessment was incorrect or absent (59.5 percent).
      CONCLUSIONS: Accreditation agencies provide transparency and insight into
      outpatient surgical mortality on a national scale. Results suggest that adoption
      of venous thromboembolism screening techniques may not be universal despite an
      existing large body of published evidence. Optimization of thromboembolism
      prevention pathways remains vital, and consideration of anticoagulation in those
      undergoing abdominoplasty may be important in lowering outpatient mortality.

PMID- 29649063
TI  - Ganoderma lucidum Polysaccharide Peptide Attenuates Skin Flap Ischemia
      Reperfusion Injury in a Thioredoxin-Dependent Manner.
AB  - BACKGROUND: Thioredoxin-1 plays an important role in protecting the skin flap
      from ischemia-reperfusion injury. Ganoderma lucidum polysaccharide peptide is the
      major component of G. lucidum, which possesses potent antioxidant and
      antiapoptotic activity. This study aims to determine whether G. lucidum
      polysaccharide peptide could attenuate skin flap ischemia-reperfusion injury and
      to investigate possible mechanisms involved. METHODS: G. lucidum polysaccharide
      peptide was administered to mice and epidermal cells before ischemia-reperfusion
      and hypoxia/reoxygenation, respectively. The thioredoxin-1 inhibitor PX-12 was
      introduced in the counterevidence group. The flap tissues and cells were tested
      by hematoxylin and eosin and immunohistochemistry staining, terminal
      deoxynucleotidyl transferase-mediated dUDP end-labeling assay, superoxide
      dismutase and malonic dialdehyde measurement, and Western blot. RESULTS: The
      survival rates of ischemia-reperfusion flaps and hypoxia/reoxygenation cells
      increased significantly following G. lucidum polysaccharide peptide treatment.
      Mitigated tissue damage, reduced apoptosis, and enhanced antioxidant activity
      were observed in ischemia-reperfusion flaps replenishing G. lucidum
      polysaccharide peptide. Western blot analysis revealed thioredoxin-1 depletion
      and a remarkable increase in ASK-1, phospho-p38, cleaved caspase-3, and cleaved
      PARP abundance in ischemia-reperfusion flaps and hypoxia/reoxygenation cells,
      whereas G. lucidum polysaccharide peptide dramatically up-regulated thioredoxin-1
      and reduced the apoptosis-related protein expression. However, the rescue effect
      of G. lucidum polysaccharide peptide was notably blunted by supplementation with
      PX-12. CONCLUSIONS: The current investigation highlights the protective role of
      G. lucidum polysaccharide peptide in skin flap ischemia-reperfusion injury
      through a thioredoxin-1-dependent antioxidant and antiapoptotic pathway. This
      initial foray demonstrates the therapeutic value of G. lucidum polysaccharide
      peptide against ischemia-reperfusion and facilitates the understanding of its
      dermoprotective mechanism.

PMID- 29649064
TI  - Incomplete Facial Paralysis: The Use of the Ipsilateral Residual Facial Nerve as
      a Donor Nerve for Facial Reanimation.
AB  - BACKGROUND: The reconstructive approach for incomplete facial paralysis is not
      yet determined. In this article, the authors present a new surgical approach for
      patients with incomplete facial paralysis in which residual, ineffective movement
      is detected preoperatively in the ipsilateral buccozygomatic territory of the
      paretic facial nerve. METHODS: Sixteen patients with incomplete facial paralysis
      were found eligible for the procedure and underwent one-stage facial reanimation
      performed by the senior author (E.G.). Reanimation was performed using free
      gracilis muscle transfer with neural coaptation to an active facial nerve
      branch(es) responsible for the predetected buccozygomatic residual movement.
      Patients were reviewed in a systematic fashion using a combined still
      photographic and video scoring scale for symmetry at rest and at dynamic states.
      RESULTS: Following surgery, improved symmetry was observed in the majority of
      observations of the mouth region at rest and while smiling and of the nasolabial
      fold region while smiling. There was no significant change in symmetry in the
      majority of observations of the eye region at rest and while smiling and the
      nasolabial fold region at rest. Video assessment of dynamic facial symmetry while
      smiling demonstrated improved symmetry in 91 percent of the observations (n = 191
      observations). Comparison of mean scores for dynamic smile symmetry produced a
      statistically significant improvement of 1.68 points following surgery (p <
      0.001). CONCLUSION: Based on this series, the authors recommend that use of the
      ipsilateral facial nerve buccozygomatic residual branch be considered as a donor
      nerve for facial reanimation using a free gracilis muscle transfer in patients
      with incomplete facial paralysis with residual preoperative movement in the
      midface. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 29649065
TI  - Ageing effect on 18F-DOPA and 123I-MIBG uptake: a cross-sectional study.
AB  - BACKGROUND: The aim of this study was to investigate the relationship between age
      and uptake of fluorine-18-L-dihydroxyphenylalanine (F-DOPA) in the brain and
      myocardial uptake of iodine-123-metaiodobenzylguanidine (I-MIBG) in normal adult
      participants. PARTICIPANTS AND METHODS: To this end, a total of 72 healthy
      participants were enroled. Of these, 37 individuals (male, 21; female, 16; mean
      age: 60+/-12 years; age range: 38-85 years) underwent F-DOPA PET/CT, whereas 35
      individuals (male, 19; female, 16; mean age: 61+/-17 years; age range: 17-87
      years) underwent I-MIBG scintigraphy. For F-DOPA PET/CT, regions of interest were
      placed on the caudate nucleus, globus pallidus and putamen by means of the WFU
      Pickatlas tool implemented in SPM8 and further analysed after a normalization
      process. For I-MIBG scintigraphy, regions of interest were set over the upper
      mediastinum and a heart-to-mediastinum count ratio was calculated. The relation
      between age and normalized F-DOPA values or heart-to-mediastinum ratio values was
      examined using correlation analysis of variance and Pearson's correlation
      coefficient. RESULTS: We did not find any significant relationship between age
      and F-DOPA and I-MIBG uptake, respectively. CONCLUSION: Our findings suggest that
      both brain F-DOPA PET/CT and cardiac I-MIBG scintigraphy represent age
      independent biomarkers whose analyses of quantitative uptake may not require
      adjustment for patients' age.

PMID- 29649066
TI  - Macrophage Polarization Favors Epithelial Repair During Acute Respiratory
      Distress Syndrome.
AB  - OBJECTIVES: Alveolar macrophage polarization and role on alveolar repair during
      human acute respiratory distress syndrome remain unclear. This study aimed to
      determine during human acute respiratory distress syndrome: the alveolar
      macrophage polarization, the effect of alveolar environment on macrophage
      polarization, and the role of polarized macrophages on epithelial repair. DESIGN:
      Experimental ex vivo and in vitro investigations. SETTING: Four ICUs in three
      teaching hospitals. PATIENTS: Thirty-three patients with early moderate-to-severe
      acute respiratory distress syndrome were enrolled for assessment of the
      polarization of alveolar macrophages. INTERVENTIONS: Polarization of acute
      respiratory distress syndrome macrophages was studied by flow cytometry and
      quantitative polymerase chain reaction. Modulation of macrophage polarization was
      studied in vitro using phenotypic and functional readouts. Macrophage effect on
      repair was studied using alveolar epithelial cells in wound healing models.
      MEASUREMENTS AND MAIN RESULTS: Ex vivo, alveolar macrophages from early acute
      respiratory distress syndrome patients exhibited anti-inflammatory
      characteristics with high CD163 expression and interleukin-10 production.
      Accordingly, early acute respiratory distress syndrome-bronchoalveolar lavage
      fluid drives an acute respiratory distress syndrome-specific anti-inflammatory
      macrophage polarization in vitro, close to that induced by recombinant
      interleukin-10. Culture supernatants from macrophages polarized in vitro with
      acute respiratory distress syndrome-bronchoalveolar lavage fluid or interleukin
      10 and ex vivo acute respiratory distress syndrome alveolar macrophages
      specifically promoted lung epithelial repair. Inhibition of the hepatocyte growth
      factor pathway in epithelial cells and hepatocyte growth factor production in
      macrophages both reversed this effect. Finally, hepatocyte growth factor and
      soluble form of CD163 concentrations expressed relatively to macrophage count
      were higher in bronchoalveolar lavage fluid from acute respiratory distress
      syndrome survivors. CONCLUSIONS: Early acute respiratory distress syndrome
      alveolar environment drives an anti-inflammatory macrophage polarization favoring
      epithelial repair through activation of the hepatocyte growth factor pathway.
      These results suggest that macrophage polarization may be an important step for
      epithelial repair and acute respiratory distress syndrome recovery.

PMID- 29649067
TI  - Outpatient Negative-Pressure Wound Therapy Following Surgical Debridement:
      Results and Complications.
AB  - OBJECTIVE: To present results and complications in a case series of outpatients
      with diabetic and neuropathic foot ulcers with exposed bone following surgical
      debridement treated with negative-pressure wound therapy (NPWT). METHODS:
      Retrospective data were obtained from digital medical records from the Maccabi
      Health Services High Risk Foot Clinic in Tel Aviv, Israel, between 2009 and 2014.
      Medical records examined were those of clinic outpatients with exposed bone
      following partial foot amputation or selective bone debridement (University of
      Texas grade III-A) treated with NPWT. MAIN OUTCOME MEASURES: Wound area, closure
      rate, and adverse events. MAIN RESULTS: There were 66 patients provided NPWT in a
      total of 77 treatment courses. Mean patient age was 62 +/- 10 years, 82% were
      male, and mean diabetes mellitus duration was 14 +/- 8 years. Mean HbA1C levels
      were 8.1% +/- 1.7%. Mean treatment course duration was 16 days (range, 2-42
      days). Wound area decreased significantly (from 11.3 +/- 16.8 cm to 8.0 +/- 13.3
      cm, P < .0001). Ulcer curing was noted in 7% of the cases, and healing
      progression was noted in 54%. Seven serious adverse events were recorded.
      CONCLUSIONS: Outpatient NPWT is a relatively safe and effective adjuvant to
      surgical debridement of neuropathic foot ulcers. In an outpatient setting, one
      can expect serious adverse events to occur in 10% of cases, but this seems
      unavoidable in patients with diabetic foot ulcers when taking into account their
      comorbidities and patient resources. Strict protocols to promote early
      recognition of complications and appropriate response to minimize deterioration
      must be implemented.

PMID- 29649068
TI  - Is Exercise the Right Medicine for Dystrophic Muscle?
AB  - INTRODUCTION: Duchenne muscular dystrophy (DMD) is a neuromuscular disease caused
      by a dystrophin protein deficiency. Dystrophin functions to stabilize and protect
      the muscle fiber during muscle contraction; thus, the absence of functional
      dystrophin protein leads to muscle injury. DMD patients experience progressive
      muscle necrosis, loss of function, and ultimately succumb to respiratory failure
      or cardiomyopathy. Exercise is known to improve muscle health and strength in
      healthy individuals as well as positively affect other systems. Because of this,
      exercise has been investigated as a potential therapeutic approach for DMD.
      METHODS: This review aims to provide a concise presentation of the exercise
      literature with a focus on dystrophin-deficient muscle. Our intent was to
      identify trends and gaps in knowledge with an appreciation of exercise modality.
      RESULTS: After compiling data from mouse and human studies, it became apparent
      that endurance exercises such as a swimming and voluntary wheel running have
      therapeutic potential in limb muscles of mice and respiratory training was
      beneficial in humans. However, in the comparatively few long-term investigations,
      the effect of low-intensity training on cardiac and respiratory muscles was
      contradictory. In addition, the effect of exercise on other systems is largely
      unknown. CONCLUSIONS: To safely prescribe exercise as a therapy to DMD patients,
      multisystemic investigations are needed including the evaluation of respiratory
      and cardiac muscle.

PMID- 29649069
TI  - Older E-bike Users: Demographic, Health, Mobility Characteristics, and Cycling
      Levels.
AB  - PURPOSE: Electric bicycles (e-bikes) may offer an opportunity to stimulate
      physical activity among older adults. The current study compared Flemish
      (Belgian) older e-bike users with those not using an e-bike on sociodemographics,
      health characteristics, and access to motorized transport. In addition, it
      examined the association between e-bike use and levels of cycling and the
      moderating effects of sex, body mass index (BMI), and cycling limitations.
      METHODS: An online or interview version of the same questionnaire was completed
      by 1146 participants. Data were analyzed using logistic regression and hurdle
      models. RESULTS: Women, those with a higher BMI, and those with one (compared
      with no) motorized vehicle in the household had higher odds of being an e-bike
      user. E-bike use was related to higher odds of having cycled for transport in the
      past week, and this relationship was stronger among those with a higher BMI (low
      BMI: odds ratio, 1.89; 95% confidence interval (CI), 1.24-2.91; high BMI: odds
      ratio, 3.34; 95% CI, 2.26-5.00). Among those who cycled for transport in the last
      week, e-bike use was associated with 35% more minutes of cycling for transport
      (95% CI, 17%-56%). E-bike use was related to 183% higher odds of having biked for
      recreation (95% CI, 115%-274%). Among women and those with cycling limitations
      who cycled for recreation in the last week, e-bike use was also related to 57%
      (95% CI, 18%-109%) and 180% (95% CI, 63%-381%) more minutes of cycling for
      recreation, respectively. CONCLUSION: E-bikes may provide an opportunity to
      promote cycling among older adults, particularly among subgroups at risk for
      physical inactivity.

PMID- 29649070
TI  - An accidentally crushed stent identified by optical coherence tomography.

PMID- 29649071
TI  - Predictors of early scaffold thrombosis: results from the multicenter prospective
      German-Austrian ABSORB RegIstRy.
AB  - BACKGROUND: In randomized clinical trials, the risk of thrombotic events with the
      absorb bioresorbable vascular scaffold (BVS) was significantly higher than with
      metallic drug-eluting stents. We evaluated predictors of scaffold thrombosis in
      the large-scale, multicenter German-Austrian ABSORB RegIstRy. METHODS AND
      RESULTS: 3178 patients with treatment of 4252 lesions using 5020 scaffolds were
      included. Follow-up rate at 6 months was 97.4%. Forty-five (1.42%) patients
      experienced definite/probable scaffold thrombosis during follow-up. Multiple
      regression analysis showed implantation of absorb BVS in bifurcation lesions
      [odds ratio (OR): 4.43; 95% confidence interval (CI): 1.69-11.59; P=0.0024] or
      treatment in the years 2013/2014 (OR: 1.88; 95% CI: 1.02-3.47; P=0.04) to be
      significant predictors of scaffold thrombosis. Excluding bifurcation lesions, the
      incidence of definite/probable scaffold thrombosis decreased from 1.8% (95% CI:
      1.17-2.64%) in 2013/2014 to 0.89% (95% CI: 0.5-1.46%) in 2015/2016. In the latter
      period, absorb BVS were implanted more often in younger patients with less
      complex de novo lesions, and debulking devices and postdilatation were used more
      frequently. Between the two treatment periods, there was a significant reduction
      in myocardial infarction (2.73-1.24%, P<0.01; OR: 0.45; 95% CI: 0.26-0.77),
      definite/probable scaffold thrombosis (1.79-0.88%, P<0.05; OR: 0.49; 95% CI: 0.26
      0.93), and target lesion failure and revascularization during follow-up.
      CONCLUSION: Improved procedural technique and more strict patient selection may
      explain a significant decrease in the absorb BVS thrombosis rates during the
      recruitment period of the large-scale German-Austrian ABSORB RegIstRy. In
      addition, treatment of bifurcation lesions was identified as an independent
      predictor of definite/probable scaffold thrombosis.

PMID- 29649072
TI  - A case-control study of risk factors for colorectal cancer in an African
      population.
AB  - The interplay between hereditary and environmental factors in the causation of
      colorectal cancer in sub-Saharan Africa is poorly understood. We carried out a
      community based case-control study to identify the risk factors associated with
      colorectal cancer in Zimbabwe. We recruited 101 cases of colorectal cancer and
      202 controls, matched for age, sex and domicile. Potential risk factors including
      family history, socioeconomic status, urbanization, diabetes mellitus and
      previous schistosomiasis were evaluated. Conditional logistic regression was used
      to estimate the odds ratios associated with the different factors. Cases were
      more likely to have a tertiary education (32.7 vs. 13.4%, P<0.001) and a higher
      income (18.8 vs. 6.9%, P=0.002). After multivariate analysis, diabetes mellitus
      [odds ratio (OR): 5.3; 95% confidence interval (CI): 1.4-19.9; P=0.012], previous
      urban domicile (OR: 2.8; 95% CI: 1.0-7.8; P=0.042), previous schistosomiasis (OR:
      2.4; 95% CI: 1.4-4.2; P=0.001) and cancer in a first-degree relative (OR: 2.4;
      95% CI: 1.2-4.8; P=0.018) were associated independently with colorectal cancer.
      Our findings suggest that family history, diabetes mellitus, previous
      schistosomiasis and approximation to a western lifestyle are the predominant
      associations with colorectal cancer in Africans. This offers opportunities for
      targeted prevention and hypothesis-driven research into the aetiology of
      colorectal cancer in this population.

PMID- 29649073
TI  - Short article: Safety of targeted prophylaxis strategy in patients with resolved
      hepatitis B virus infection receiving rituximab for immune-mediated diseases.
AB  - OBJECTIVES: Rituximab (RTX) is a monoclonal antibody that is widely used in
      hematologic malignancies and immune-mediated diseases (IMID) and has been
      associated with the risk of hepatitis B virus reactivation (HBVr). Thus,
      antiviral prophylaxis is recommended before RTX treatment in all patients with
      chronic hepatitis B virus (HBV) infection and those with resolved infection
      affected by onco-hematological conditions. By contrast, the correct management of
      HBsAg-negative/HbcAb-positive patients candidates for RTX-containing regimens for
      IMID is still debated, owing to few data currently available in this setting.
      PATIENTS AND METHODS: We retrospectively evaluated the risk of HBVr in patients
      with IMID with resolved HBV infection, referred to the Infectious and Tropical
      Diseases Unit Outpatients Service, Careggi Hospital, Florence, Italy, between
      September 2013 and September 2017, undergoing RTX without antiviral prophylaxis
      and followed up by serial serum HBV-DNA monitoring. RESULTS: Overall, 20 patients
      with IMID were identified (70% female, with median age of 57 years) and followed
      up for a median period of 19 months (range: 2-36 months). A single HBVr case,
      detected in preclinical stage, was observed (1/20, 5%), and targeted prophylaxis
      was promptly introduced. CONCLUSION: The results supported the low to moderate
      risk of HBVr in HBsAg-negative/HBcAb-positive patients with IMID undergoing RTX,
      in contrast to what is observed in onco-hematological settings. The targeted
      prophylaxis strategy, based on serum HBV-DNA serial monitoring, seems a safe
      option in these patients.

PMID- 29649074
TI  - Parental Bereavement in Young Children Living in South Africa and Malawi:
      Understanding Mental Health Resilience.
AB  - BACKGROUND: Parental loss is a major stressful event found to increase risk of
      mental health problems in childhood. Yet, some children show resilient adaptation
      in the face of adversity across time. SETTING: This study explores predictors of
      mental health resilience among parentally bereaved children in South Africa and
      Malawi and their cumulative effect. The study also explores whether predictors of
      resilience differed between orphaned and nonorphaned children. METHODS:
      Consecutive attenders of community-based organizations (children; 4-13 years, and
      their caregivers) were interviewed at baseline and 15- to 18-month follow-up (n =
      833). Interviews comprising inventories on demographic information, family data,
      child mental health, bereavement experience, and community characteristics.
      Mental health screens were used to operationalize resilience as the absence of
      symptoms of depression, suicidality, trauma, emotional, and behavioral problems.
      RESULTS: Almost 60% of children experienced parental loss. One-quarter of
      orphaned children showed no mental health problems at either wave and were
      classified as resilient. There were equal proportions of children classified as
      resilient within the orphaned (25%) versus nonorphaned group (22%). Being a quick
      learner, aiding ill family members, positive caregiving, household employment,
      higher community support, and lower exposure to domestic violence, physical
      punishment, or stigma at baseline predicted sustained resilience. There were
      cumulative influences of resilience predictors among orphaned children.
      Predictors of resilience did not vary by child age, sex, country of residence or
      between orphaned and nonorphaned children. CONCLUSIONS: This study enhances
      understanding of resilience in younger children and identifies a number of
      potential environmental and psychosocial factors for bolstering resilience in
      orphaned children.

PMID- 29649075
TI  - Barriers to HIV Testing Among Men Who Have Sex With Men in India Reached Online:
      Implications for Interventions.

PMID- 29649076
TI  - Pharmacokinetics of Tenofovir Alafenamide When Coadministered With Other HIV
      Antiretrovirals.
AB  - BACKGROUND: Tenofovir alafenamide (TAF), a prodrug of the nucleotide analogue
      tenofovir (TFV), is an antiretroviral (ARV) agent approved either as a complete
      regimen [elvitegravir/cobicistat/emtricitabine (F)/TAF, rilpivirine/F/TAF,
      bictegravir/F/TAF], or for use with other ARVs (F/TAF), for treatment of HIV. TAF
      is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein
      (BCRP) transporters. Disposition of TAF may be altered by comedications that can
      inhibit or induce P-gp or BCRP transporters. The effects of ARVs on the
      pharmacokinetics of TAF were evaluated in 3 studies. METHODS: Healthy
      participants received TAF administered alone or with rilpivirine in study 1, with
      dolutegravir, ritonavir-boosted atazanavir (ATV + RTV), lopinavir (LPV/RTV), or
      darunavir (DRV + RTV) in study 2, and with the pharmacokinetic enhancer
      cobicistat or efavirenz in study 3. RESULTS: Across the 3 studies, 98
      participants received treatment with TAF and a coadministered agent (n = 10
      34/cohort). All study treatments were well tolerated. TAF and TFV exposures were
      unaffected after co-administration with rilpivirine and dolutegravir.
      Coadministration with P-gp/BCRP inhibitors such as cobicistat or PI-based
      regimens (ATV + RTV, LPV/r, or DRV + RTV) resulted in a range of 6%-183%
      increases in TAF and 105%-316% increases in TFV exposure, whereas
      coadministration with a P-gp inducer, efavirenz, resulted in a 15%-24% decrease
      in TAF and TFV exposure. CONCLUSIONS: Evaluation of the drug interaction between
      TAF and other commonly prescribed boosted and unboosted ARVs provides
      characterization of the susceptibility of TAF and/or TFV pharmacokinetics to
      inhibitors or inducers of P-gp/BCRP transporters.

PMID- 29649077
TI  - Circulating CXCR5-Expressing CD8+ T-Cells Are Major Producers of IL-21 and
      Associate With Limited HIV Replication.
AB  - BACKGROUND: Despite advances made with the highly active antiretroviral therapy
      (HAART) in the control of the HIV 1 infection, a cure has not been achieved
      because of the persistence of viral reservoirs. The major HIV reservoirs remain
      in the lymphoid follicles because of, among other factors, the partial absence of
      CD8 T-cells in these structures. Recently, lymphoid follicle-confined and
      circulating CD8 T-cells expressing the C-X-C chemokine receptor type 5 (CXCR5)
      were described, possessing antiviral mechanisms that could help to control HIV
      replication. SETTING AND METHODS: By flow cytometry, we characterized the
      phenotype and function of circulating CXCR5-expressing CD8 T-cells in HIV
      infected patients with natural or HAART-induced control of HIV replication.
      RESULTS: Circulating CXCR5-expressing CD8 T-cells exhibited low or null
      expression of the C-C chemokine receptor type 7 (CCR7) and had a transitional
      memory phenotype. Particular redistributions of CXCR5-expressing CD8 T-cells were
      found in HIV-infected patients, and they were partially restored by HAART. The
      frequency of CXCR5CCR7 CD8 T-cells was higher in spontaneous HIV controllers and
      negatively correlated with plasma HIV RNA levels. Total and HIV-specific CXCR5
      CD8 T-cells were major producers of interleukin-21, and this function was
      positively associated with their interferon-gamma production. CONCLUSIONS:
      Circulating CXCR5-expressing CD8 T-cells are associated with low-level HIV
      replication; these cells could be novel correlates of protection, and potentially
      useful in the eradication of HIV reservoirs.

PMID- 29649078
TI  - Point of Diagnosis and Patient Retention in HIV Care in Western Kenya.
AB  - BACKGROUND: Home-based counseling and testing (HBCT) achieves earlier HIV
      diagnosis than other testing modalities; however, retention in care for these
      healthier patients is unknown. The objective of this study was to determine the
      association between point of HIV testing and retention in care and mortality.
      SETTING: Academic Model Providing Access to Healthcare (AMPATH) has provided HIV
      care in western Kenya since 2001. METHODS: AMPATH initiated HBCT in 2007. This
      retrospective analysis included individuals 13 years and older, enrolled in care
      between January 2008 and September 2016, with data on point of testing. Discrete
      time multistate models were used to estimate the probability of transition
      between the following states: engaged, disengaged, transfer, and death, and the
      association between point of diagnosis and transition probabilities. RESULTS:
      Among 77,358 patients, 67% women, median age: 35 years and median baseline CD4:
      248 cells/mm. Adjusted results demonstrated that patients from HBCT were less
      likely to disengage [relative risk ratio (RRR) = 0.87, 95% CI: 0.83 to 0.91] and
      die (RRR = 0.65, 95% CI: 0.55 to 0.75), whereas those diagnosed through provider
      initiated counseling and testing were more likely to disengage (RRR = 1.09, 95%
      CI: 1.07 to 1.12) and die (RRR = 1.13, 95% CI: 1.06 to 1.20), compared with
      patients from voluntary counseling and testing. Once disengaged, patients from
      HBCT were less likely to remain disengaged, compared with patients from voluntary
      counseling and testing. CONCLUSIONS: Patients entering care from different HIV
      testing programs demonstrate differences in retention in HIV care over time
      beyond disease severity. Additional research is needed to understand the patient
      and system level factors that may explain the associations between testing
      program, retention, and mortality.

PMID- 29649079
TI  - In Search of Mobile Applications for Urogynecology Providers.
AB  - INTRODUCTION: Thousands of medical applications (apps) are available for mobile
      devices. Finding accurate, health care provider-centered apps may be time
      consuming and frustrating for urogynecologists. The objective of this study was
      to identify and evaluate urogynecology (urogyn) apps using a modified
      APPLICATIONS scoring system. MATERIALS AND METHODS: Urogyn apps were identified
      from the Apple iTunes and Google Play Stores using the following 10 MeSH terms:
      urogynecology, incontinence, prolapse, urinary tract infection, pelvic surgery,
      fecal incontinence, defecation disorder, voiding disorder, urethral diverticulum,
      and fistula. Patient-centered and inaccurate apps were excluded. The remaining
      apps were evaluated with a modified APPLICATIONS scoring system, which included
      both objective and subjective criteria to determine each app's ability to aid in
      clinical decision making and to provide informational data. Objective rating
      components were price, paid subscription, literature referenced, in-app
      purchases, Internet connectivity, advertisements, text search field,
      interplatform compatibility and incorporated images, figures, videos, and special
      features. Subjective rating components were ease of navigation and presentation.
      RESULTS: Our search yielded 133 and 235 apps in the Apple iTunes and Google Play
      Stores, respectively. Only 8 apps (4 of which were in both stores) were
      determined to be accurate and useful; these were evaluated using the modified
      APPLICATIONS scoring system. The top-rated app was Practical Urology. CONCLUSION:
      Few accurate clinical decision-making and informational apps exist for
      urogynecologists. Apps varied by comprehensiveness and quality. This study
      highlights the importance of systematically reviewing and rating medical apps. It
      also emphasizes the need for developing accurate apps for urogynecologists that
      improve health care provider performance and patient outcomes.

PMID- 29649080
TI  - Investigating Changes in Weight and Body Composition Among Women in Adjuvant
      Treatment for Breast Cancer: A Scoping Review.
AB  - BACKGROUND: Despite several investigations, findings on weight changes during and
      after adjuvant treatment for breast cancer are diverse and point in several
      directions. OBJECTIVE: The aims of this study were to investigate changes in
      weight and body composition associated with contemporary anticancer medication
      and to examine factors that might influence the assessment and diversity of the
      findings. METHODS: This article used the method of a scoping review to map the
      body of literature. From searching the databases PubMed, CINAHL, and EMBASE using
      MeSH terms, CINAHL terms, and Emtree, as well as free text, 19 articles were
      selected for further investigation. RESULTS: The scoping review illustrates how
      findings in weight and body composition changes fluctuate over time as
      illustrated in 4 measure points: short term, 1 year, 18 months/2 years, and long
      term. The studies displayed differences regarding study designs, sample sizes,
      treatment regimens, measure points and techniques, and cutoff values for
      assessing weight changes, which make it difficult to synthesize findings and
      provide strong evidence for use in clinical practice. CONCLUSION: Synthesizing
      findings over time illustrates the need for attention on younger premenopausal
      women given chemotherapy. Weight need to be monitored for at least 2 years as
      short-term changes may be caused by increased body water, whereas long-term
      changes seem to be related with increased fat mass essential for risking
      recurrence and early death. IMPLICATIONS FOR PRACTICE: The diversity in methods
      discloses the need for the research community to reach consensus regarding study
      designs for future research in this area.

PMID- 29649081
TI  - Psychometric Testing of the European Organisation for Research and Treatment of
      Cancer Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy
      20-Item Scale Using Pooled Chemotherapy-Induced Peripheral Neuropathy Outcome
      Measures Standardization and Alliance for Clinical Trials in Oncology A151408
      Study Data.
AB  - BACKGROUND: No criterion-standard patient-reported outcome measure of
      chemotherapy-induced peripheral neuropathy (CIPN) exists. OBJECTIVES: The aims of
      this study were to reevaluate the sensitivity, reliability, and validity of the
      European Organisation for Research and Treatment of Cancer Quality of Life
      Questionnaire-CIPN (QLQ-CIPN20) measure and suggest possible revisions that could
      strengthen it. METHODS: Cross-sectional QLQ-CIPN20 data from 8 European countries
      (n = 271) were pooled with data from 4 North American multisite CIPN intervention
      trials (n = 884). The combined sample (N = 1155) included patients with varied
      cancer diagnoses who had received neurotoxic chemotherapy. Item score ranges,
      Cronbach's alpha, and exploratory factor analysis were used to evaluate
      sensitivity, internal consistency, and structural validity. RESULTS: Individual
      item mean scores ranged from 1.21 to 2.34 (SD range, 0.55-1.17). All item scores
      encompassed the entire 1 to 4 range. We recommend that 4 items be removed because
      of low item-item score correlations (r < 0.30). On the basis of the remaining 16
      items, 88% of the variance was explained by 2 factors whose Cronbach's alpha
      coefficients were .90 and .85. However, items lacked conceptual alignment with
      previously published factor structures. CONCLUSION: Using a large, diverse sample
      of European and North American participants, the reduced 16-item QLQ-CIPN20 is
      sensitive and internally consistent. However, factor analysis results revealed an
      unstable factor structure. IMPLICATIONS FOR PRACTICE: The use of a reliable,
      valid, and sensitive criterion-standard QLQ-CIPN20 variant in clinical practice
      settings could improve function, quality of life, and CIPN symptom control by
      facilitating patient reporting and thereby clinician awareness of this
      underrecognized consequence of cancer therapy.

PMID- 29649082
TI  - Transcutaneous Electrical Nerve Stimulation Reduces Resting Pain in Head and Neck
      Cancer Patients: A Randomized and Placebo-Controlled Double-Blind Pilot Study.
AB  - BACKGROUND: Individuals receiving radiation for head and neck cancer (HNC) often
      develop painful oral mucositis that impairs function, possibly leading to feeding
      tubes, hospitalization, and treatment delays. Although pharmacologic medications
      provide some relief, many report inadequate analgesia and adverse effects.
      Transcutaneous electrical nerve stimulation (TENS) is a safe, nonpharmacologic
      intervention; it decreases pain and analgesics and improves function, yet no
      studies examined TENS for HNC. OBJECTIVE: The aim of this study was to examine
      the efficacy of TENS for pain and function in HNC patients. METHODS: This study
      used a randomized, double-blinded crossover design; participants received 3 TENS
      treatments during weeks 4 to 6 of radiation: active, placebo, and no TENS over
      the temporomandibular joint and upper cervical region. Pain (McGill Pain
      Questionnaire, visual analog scale [VAS] resting and function), function (mouth
      opening, tongue movement, speaking), fatigue (VAS), and treatment effectiveness
      (VAS) were assessed before and after TENS at 3 visits. RESULTS: Resting pain
      (McGill Pain Questionnaire and VAS) decreased significantly more after active
      TENS than placebo or no TENS; changes in function and pain with function did not
      differ between conditions. Active TENS decreased fatigue significantly more than
      no TENS and was rated as more effective than placebo TENS. CONCLUSION:
      Transcutaneous electrical nerve stimulation improves pain in HNC patients
      receiving radiation but not function or pain with function relative to placebo or
      no TENS. IMPLICATIONS FOR PRACTICE: Transcutaneous electrical nerve stimulation
      may be a viable tool for radiation-induced HNC pain to complement pharmacologic
      approaches. This nonpharmacologic intervention could decrease the debilitating
      effects of radiation and analgesics, and improve quality of life. Clinical trials
      should examine the effects and safety of repeated, daily TENS in HNC patients
      receiving radiation.

PMID- 29649083
TI  - Targeted Distraction: Spinal Growth in Children With Early-Onset Scoliosis
      Treated With a Tail-gating Technique for Magnetically Controlled Growing Rods.
AB  - STUDY DESIGN: Prospective cohort study OBJECTIVE.: To understand the efficacy of
      a tail-gating technique (TGT) to mirror the normal spinal growth of children with
      early-onset scoliosis (EOS) treated with magnetically controlled growing rods
      (MCGR). SUMMARY OF BACKGROUND DATA: MCGR allow outpatient distraction and guided
      spinal growth without the need for repeat surgery. Two techniques (maximal and
      targeted) are currently employed to determine the distraction amount, however the
      efficacy of each is unknown. This study specifically assesses the ability of
      targeted distraction to achieve physiological growth. METHODS: We performed a
      retrospective review of European children treated with MCGR using a TGT and
      analyzed the post-operative clinical and radiographic outcomes, including the
      sitting height, standing height, coronal Cobb angle, T1-T12 and T1-S1 height.
      Furthermore, we compared the post-operative sitting/standing height ratio every 6
      months to those reported for normal age- and sex-matched European children.
      RESULTS: Thirty-five children were included with a mean follow-up of 3.4 years
      (1.8-5.8 years). All clinical and radiographic parameters significantly (P <
      0.05) improved immediately post-operatively and were maintained until final
      follow-up. The TGT mirrored the normative sitting/standing height ratios for
      expected spinal growth (Pearson correlation 0.95 for males and 0.90 for females).
      The mean difference between the reference values for the sitting/standing height
      ratio and our results was 0.0124 (P < 0.001) for males and 0.0068 (P = 0.010) for
      females. CONCLUSION: MCGR can reliably improve the coronal deformity in children
      with EOS while maintaining spinal growth. A TGT to determine the distraction
      amount at follow-up accurately mirrors the normal growth pattern of age-, sex-,
      and ethnicity-matched children. However, patients treated with this technique
      have a statistically significant, but clinically insignificant, shorter than
      physiologically normal spinal height. LEVEL OF EVIDENCE: 3.

PMID- 29649084
TI  - Vertebral Augmentation can Induce Early Signs of Degeneration in the Adjacent
      Intervertebral Disc: Evidence from a Rabbit Model.
AB  - STUDY DESIGN: An experimental study. OBJECTIVE: The aim of this study was to
      determine the effect of polymethylmethacrylate (PMMA) augmentation on the
      adjacent disc. SUMMARY OF BACKGROUND DATA: Vertebral augmentation with PMMA
      reportedly may predispose the adjacent vertebra to fracture. The influence of
      PMMA augmentation on the adjacent disc, however, remains unclear. METHODS: Using
      a retroperitoneal approach, PMMA augmentation was performed for 23 rabbits. For
      each animal, at least one vertebra was augmented with 0.2 to 0.3 mL PMMA. The
      disc adjacent to the augmented vertebra and a proximal control disc were studied
      using magnetic resonance (MR) imaging, histological and molecular level
      evaluation at 1, 3, and 6 months postoperatively. Marrow contact channels in the
      endplate were quantified in histological slices and number of invalid channels
      (those without erythrocytes inside) was rated. Terminal deoxynucleotidyl
      transferase-mediated dUTP nick-end labeling (TUNEL) was performed to determine
      disc cell apoptosis. RESULTS: On MR images, the signal and height of the adjacent
      disc did not change 6 months after vertebral augmentation. Histological scores of
      the adjacent disc increased over time, particularly for the nucleus pulposus. The
      adjacent disc had greater nucleus degeneration score than the control disc at 3
      months (5.7 vs. 4.5, P < 0.01) and 6 months (6.9 vs. 4.4, P < 0.001). There were
      more invalid marrow contact channels in the endplate of augmented vertebra than
      the control (43.3% vs. 11.1%, P < 0.01). mRNA of ADAMTS-5, MMP-13, HIF-1alpha,
      and caspase-3 were significantly upregulated in the adjacent disc at 3 and 6
      months (P < 0.05 for all). In addition, there were more TUNEL-positive cells in
      the adjacent disc than in the control disc (43.4% vs. 24.0%, P < 0.05) at 6
      months postoperatively. CONCLUSION: Vertebral augmentation can induce early
      degenerative signs in the adjacent disc, which may be due to impaired nutrient
      supply to the disc. LEVEL OF EVIDENCE: N/A.

PMID- 29649086
TI  - The Morphology and Clinical Significance of the Extraforaminal Ligaments at the
      T1-T12 Levels.
AB  - STUDY DESIGN: A dissection-based study of 10 embalmed human cadavers. OBJECTIVE:
      The purpose of this study was to describe the extraforaminal ligaments in the
      exit regions of the T1-T12 intervertebral foramina and to discuss their possible
      clinical significance. SUMMARY OF BACKGROUND DATA: The ligaments at the lumbar
      intervertebral foramina have been well studied. However, detailed descriptions of
      the extraforaminal ligaments at the T1-T12 levels are lacking. METHODS: Two
      hundred forty T1-T12 intervertebral foramina from 10 embalmed cadavers were
      studied. The presence of the ligament was noted. The quantity, morphology,
      distributions, proximal attachments, distal attachments, and spatial orientations
      of the extraforaminal ligaments in the exit regions of the T1-T12 intervertebral
      foramina were examined. The length, width, diameter, and thickness of the
      ligaments were measured with digital calipers by three independent investigators.
      RESULTS: A total of 564 extraforaminal ligaments were identified in the 229
      intervertebral foramina; no ligaments were found in the other 11 intervertebral
      foramina, resulting in an occurrence rate of extraforaminal ligaments of 95.42%.
      One hundred thirty-six (24.11%) of the extraforaminal ligaments were radiating
      ligaments, and 428 (75.89%) were transforaminal ligaments. Radiating ligaments
      had a tendency to be abundant at T1 and T9-T12 and sparse at T2-T8. There were
      245 (43.44%) ligaments at the anterior aspect of the exit regions of the
      intervertebral foramina, 225 (39.89%) ligaments at the posterior aspect, 64
      (11.35%) ligaments at the inferior aspect, and 30 (5.32%) ligaments at the
      superior aspect. CONCLUSION: In the exit region of thoracic intervertebral
      foramina, there are two types of extraforaminal ligaments. They may serve as a
      protective mechanism against traction and play a role in the positioning of the
      nerves in the intervertebral foramen. Transforaminal ligaments may be an
      underlying cause of rib or chest pain after thoracic fracture and may be of
      clinical importance to surgeons. LEVEL OF EVIDENCE: N/A.

PMID- 29649085
TI  - Tract-Specific Volume Loss on 3T MRI in Patients With Cervical Spondylotic
      Myelopathy.
AB  - STUDY DESIGN: Case-control. OBJECTIVE: The aim of this study was to understand
      the role of high-resolution magnetic resonance (MR) in identifying regional cord
      volume loss in cervical spondylotic myelopathy (CSM). SUMMARY OF BACKGROUND DATA:
      Preliminary studies suggest that compression of the ventral region of the cord
      may contribute disproportionately to CSM symptomology; however, tract-specific
      data are lacking in the CSM population. The current study is the first to use 3T
      MR imaging (MRI) images of CSM patients to determine specific volume loss at the
      level of detail of individual descending white matter tracts. METHODS: Twelve
      patients with CSM and 14 age-matched were enrolled prospectively and underwent 3
      Tesla MRI of the cervical spine. Using the high-resolution images of the spinal
      cord, straightening and alignment with a template was performed and specific
      spinal cord tract volumes were measured using Spinal Cord Tool-box version 3.0.7.
      Modified Japanese orthopedic association (mJOA) and Nurick disability scores were
      collected in a prospective manner and were analyzed in relation to descending
      spinal tract volumes. RESULTS: Having CSM was predicted by anterior/posterior
      diameter, eccentricity of the cord [odds ratio (OR) 0.000000621, P = 0.004],
      ventral reticulospinal tract volume (OR 1.167, P = 0.063), lateral corticospinal
      tract volume (OR 1.034, P = 0.046), rubrospinal tract volume (OR 1.072, P =
      0.011), and ventrolateral reticulospinal tract volume (OR 1.474, P = 0.005) on
      single variable logistic regression. Single variable linear regression showed
      decreases in anterior/posterior spinal cord diameter (P = 0.022), ventral
      reticulospinal tract volumes (P = 0.007), and ventrolateral reticulospinal tract
      volumes (P = 0.017) to significantly predict worsening mJOA scores. Similarly,
      decreases in ventral reticulospinal tract volumes significantly predicted
      increasing Nurick scores (P = 0.039). CONCLUSION: High-resolution 3T MRI can
      detect tract-specific volume loss in descending spinal cord tracts in CSM
      patients. Anterior/posterior spinal cord diameter, ventral reticulospinal tract,
      ventrolateral reticulospinal tract, lateral corticospinal tract, and rubrospinal
      tract volume loss are associated with CSM symptoms. LEVEL OF EVIDENCE: 2.

PMID- 29649087
TI  - Activity of Daily Living After Long Level Fusion in Adult Spinal Deformity:
      Compared With Over 60-Year-Old Degenerative Spine Patients Without Adult Spinal
      Deformity.
AB  - STUDY DESIGN: Prospective single center study. OBJECTIVE: The aim of this study
      was to evaluate 1) the activity of daily living (ADL) of three categorized
      patients group; over 60-year-old degenerative spine patients without adult spinal
      deformity (ASD), nonoperative ASD patients, and operative ASD patients, 2) what
      kinds of activities would be impaired, and 3) how the ADL changes over time after
      long level fusion. SUMMARY OF BACKGROUND DATA: There is still debate how surgeons
      could decide treatment methods for old-aged adult spinal deformity, operatively
      or not. There was lack of information how long level fusion impacts daily
      activities, especially sedentary Asian lifestyle. In Asia, impaired ADL is much
      more important issue because of different lifestyle. METHODS: Patients were
      categorized into three groups; Group 1 was over 60-year old aged degenerative
      spine disease without deformity, Group 2 was ASD patients who did not have
      surgery, and Group 3 was ASD patients who had surgery for deformity correction.
      Patients were evaluated using answer Oswestry Low Back Pain Disability
      Questionnaire, and Assessment activities of daily living for sedentary Asian
      culture (ADL-SA) questionnaire. RESULTS: Group 1 showed nearly full functions in
      every activity (ADL-SA: 41.4). ADL-SA scores of Group 2 were similar to Group 1
      (P = 0.452). However, get up from bottom (P < 0.001), and pick up object (P <
      0.001) were impaired. After long level fusion, ADL was impaired but gradually
      improved by time. From postoperative 1 year, total ADL score recovered to
      acceptable range. However, among ADL, activities associated sedentary lifestyle
      (get up from bottom, wipe floor, pick up object, and sit cross-legged) were still
      impaired after 2 years postoperatively. CONCLUSION: ADL was impaired after long
      level fusion; however it would improve as time goes by. However, among ADL,
      activities associated sedentary lifestyle was still impaired. Hence give enough
      information to patients about limited activities before deciding operation. LEVEL
      OF EVIDENCE: 3.

PMID- 29649088
TI  - Alterations in Intramedullary T2-weighted Increased Signal Intensity following
      Laminoplasty in Cervical Spondylotic Myelopathy Patients: Comparison Between Pre-
      and Postoperative Magnetic Resonance Images.
AB  - STUDY DESIGN: A prospective comparative imaging study. OBJECTIVE: This study
      investigated whether the postoperative classification of and alterations in
      increased signal intensity (ISI) of the spinal cord reflected the postoperative
      severity of symptoms and surgical outcomes in cervical spondylotic myelopathy
      (CSM) patients. SUMMARY OF BACKGROUND DATA: Although ISI on performing magnetic
      resonance imaging (MRI) is observed in CSM patients, alterations in ISI have not
      been investigated. The association of postoperative ISI with surgical outcomes in
      CSM patients remains controversial. METHODS: Totally, 505 consecutive CSM
      patients (311 males) with a mean age of 66.6 (range, 41-91) years were enrolled.
      All were treated with laminoplasty and underwent MRI scans: preoperatively and
      after an average of 26.5 months postoperatively (range 12-66 months). ISI was
      classified pre- and postoperatively into three groups based on sagittal T2
      weighted magnetic resonance images: Grade 0, none; Grade 1, light (obscure); and
      Grade 2, intense (bright). The patients' pre- and postoperative neurological
      statuses were evaluated using the Japanese Orthopaedic Association scoring system
      for cervical myelopathy (JOA score) and other quantifiable tests, including the
      10-s grip and release (10-s G&R) test and 10-s step test. RESULTS:
      Preoperatively, 168 patients had Grade 0 ISI, 169 had Grade 1, and 168 had Grade
      2; postoperatively, 210 patients had Grade 0 ISI, 94 had Grade 1, and 201 had
      Grade 2. Patients with postoperative Grade 0 ISI had a better postoperative JOA
      score, recovery rate, and 10-s G&R and 10-s step test scores than those with
      other grades. The postoperative ISI grade improved in 66 patients (13.1%),
      worsened in 57 (11.3%), and remained unchanged in 382 (75.6%). CONCLUSION:
      Postoperative ISI partially reflects postoperative symptoms and surgical
      outcomes. Alterations in ISI were observed postoperatively in 123 patients
      (24.4%) and were not correlated with surgical outcomes. LEVEL OF EVIDENCE: 2.

PMID- 29649089
TI  - Prognostic Factors of Patients With Malignant Epithelioid Vascular Tumors in the
      Spine: Retrospective Analysis of 46 Patients in a Single Center.
AB  - STUDY DESIGN: A retrospective study of 46 patients with malignant epithelioid
      vascular tumors (MEVT) in the spine was performed. OBJECTIVE: The purpose of this
      study was to illustrate the clinic characteristics of MEVT in the spine and to
      discuss prognostic factors by survival analysis. SUMMARY OF BACKGROUND DATA: MEVT
      in the spine is relatively uncommon, and there is little published information
      regarding this subject. Therefore, prognostic factors of this disease are still
      controversial. METHOD: The univariate and multivariate analysis of various clinic
      characteristics were performed to identify the independent factor that affects
      prognosis for patients with MEVT in the spine who underwent surgical treatment in
      Changzheng Hospital Orthopedics Oncological Center (CHOOC) between 2005 and 2015.
      Disease-free survival (DFS) and overall survival (OS) were estimated by Kaplan
      Meier method to identify potential prognostic factors. Factors with P values of
      0.1 or less were subjected to multivariate analysis by Cox regression analysis. P
      values of 0.05 or less was considered statistically significant. RESULT: A total
      of 46 patients with MEVT in the spine were included in the study. The mean follow
      up period was 42.6 months (range, 5-143 mo). Recurrence was detected in 22
      patients after initial surgery in our center, whereas death in 18 patients. The
      univariate analysis suggested that age (<30 yr/>=30 yr), metastasis, preoperative
      Frankel score, postoperative Frankel score, malignant grade and resection mode
      were potential prognostic factors for DFS and OS. However, as they were submitted
      to multivariate analyses, only malignant grade and resection mode were
      independent prognostic factors. CONCLUSION: Total en bloc spondylectomy can
      significantly improve DFS for MEVT in the spine and low-grade malignancy was
      favorable factor for DFS. Total spondylectomy and low-grade malignancy
      considerably improve OS for patients with MEVT in the spine. LEVEL OF EVIDENCE:
      4.

PMID- 29649090
TI  - Reliability of Rod Lengthening, Thoracic, and Spino-Pelvic Measurements on
      Biplanar Stereoradiography in Patients Treated With Magnetically Controlled
      Growing Rods.
AB  - STUDY DESIGN: Cross-sectional study. OBJECTIVE: To assess the inter- and
      intraobserver reliability of thoracic, spino-pelvic, and rod lengthening
      measurements made on biplanar spinal stereoradiography (EOS imaging) in children
      treated with magnetically controlled growing rod (MCGR). SUMMARY OF BACKGROUND
      DATA: MCGR treatment aims to gain spine length while gradually correcting the
      spinal deformity. Monitoring thoracic and spino-pelvic parameters is crucial for
      successful management. EOS imaging is widely used for diagnosis and monitoring of
      children with Early Onset Scoliosis. However, there is a paucity of literature on
      the reliability of thoracic and spino-pelvic parameters on EOS imaging in
      children treated with MCGR. METHODS: Three independent reviewers independently
      read a random assortment of 20 whole spine posteroanterior and lateral
      radiographs from patients treated with MCGR. The measurements were repeated 4
      weeks after the initial read. The following radiological parameters were
      measured: Cobb angle of the main and compensatory curves, coronal balance,
      coronal T1-S1 and T1-T12 length, chest width and depth at T6, pelvic inlet width,
      MCGR distracted lengths, global kyphosis, proximal and distal junctional angle,
      lordosis, sagittal balance, pelvic incidence, pelvic tilt and sacral slope.
      Statistical analysis was performed with paired t test and Cronbach alpha for
      inter- and intraobserver reliability. RESULTS: All measurements had good or
      excellent intra- and interobserver reliability (alpha>0.8; P < 0.05), except
      measurements of the proximal junctional angle which showed only poor intra- and
      interobserver reliability for patients with an upper instrumented vertebra
      cranial to T4. CONCLUSION: EOS imaging is reliable for diagnosis and monitoring
      of children with Early Onset Scoliosis treated with MCGR. EOS imaging is
      particularly excellent for assessment of MCGR lengthening. Diagnosis and
      interpretation of early proximal junctional kyphosis within the cervicothoracic
      junction should be made with caution. LEVEL OF EVIDENCE: 3.

PMID- 29649091
TI  - The Prognostic Significance of Pedicle Enhancement from Contrast-enhanced MRI for
      the Further Collapse in Osteoporotic Vertebral Compression Fractures.
AB  - STUDY DESIGN: A retrospective observational study. OBJECTIVE: The aim of this
      study was to investigate the prognostic significance of contrast-enhanced
      magnetic resonance imaging (MRI) for detecting pedicle enhancement and predicting
      future collapse in patients with acute benign osteoporotic vertebral compression
      fracture (OVCF). SUMMARY OF BACKGROUND DATA: Traditional morphological
      classification regarding compression versus burst fractures cannot accurately
      anticipate the prognosis of further collapse. Identifying subgroups with a higher
      risk for further collapse may be beneficial in determining the treatment
      modality, which should be decided immediately after the injury. METHODS: One
      hundred fourteen patients with benign OVCFs who, at the onset, underwent contrast
      enhanced spine MRI between 2003 and 2016 were retrospectively analyzed. Patients
      were recruited on the basis of predefined inclusion and exclusion criteria. The
      primary outcome was the compression progression rate; other potential variables
      included demographic and clinical characteristics, initial compression rates, and
      kyphotic angles. In addition, other structural abnormalities on MRI were
      assessed. The compression progression rates were compared according to pedicle
      enhancement, and the prognostic significance of pedicle enhancement for further
      collapse were analyzed. RESULTS: Further compression progression rates were
      significantly higher in the pedicle-enhanced (PE) group than in the nonenhanced
      (NE) group. Multivariate logistic analysis revealed that pedicle enhancement may
      be associated with further compression progression >=10%. The vertebral
      augmentation (VAG) protective effect against collapse was only significant within
      the PE group, while bone densitometry and patients' mobility were significant
      only within the NE group. The log-rank test revealed a statistically significant
      difference in the rates of further collapse >=10% during the 1 year between the
      groups. CONCLUSION: Sign of pedicle enhancement is a potential risk factor for
      further compression progression. Contrast-enhanced MRI should be performed at the
      onset to better determine the future risk of collapse and to choose a better
      treatment modality for benign OVCF patients. LEVEL OF EVIDENCE: 3.

PMID- 29649092
TI  - Ascorbic Acid Attenuates Multifidus Muscles Injury and Atrophy After Posterior
      Lumbar Spine Surgery by Suppressing Inflammation and Oxidative Stress in a Rat
      Model.
AB  - STUDY DESIGN: A rat model of multifidus muscles injury and atrophy after
      posterior lumbar spine surgery. OBJECTIVE: We determined the effect of ascorbic
      acid (AA) on the postoperative multifidus muscles in rat model. SUMMARY OF
      BACKGROUND DATA: Previous studies show oxidative stress and inflammation are two
      main molecular mechanisms in multifidus muscle injury and atrophy after posterior
      lumbar surgery. AA may have a protective effect in postoperative multifidus
      muscles. METHODS: Rats were divided into sham surgery, control surgery, and
      surgery plus AA groups. Multifidus muscles of the control and AA groups were
      excised from the osseous structures. The muscles were retracted continuously for
      2 hours. In the sham and AA groups, AA was administered via oral gavage daily in
      the first week. In each group, the oxidative stress was evaluated by measuring
      malondialdehyde (MDA) and Total superoxide dismutase (T-SOD). The inflammation,
      fat degeneration, or fibrosis of multifidus muscle were evaluated by quantitative
      real-time polymerase chain reaction (q-PCR), histology, or immunohistochemical
      analysis. RESULTS: T-SOD activity was significantly lower in the control group
      than that in the AA group in the first week. MDA levels were significantly higher
      in the AA group. Interleukin-6 and tumor necrosis factor-alpha in multifidus
      muscles also showed significant differences when treated with AA. The
      inflammation score on histology was significantly lower in the AA group
      postoperatively in the first week. In the long run, marker genes for fibrosis and
      fat degeneration, and fibrosis and fat degeneration scores, were significantly
      lower in the AA than the control group on days 14 and 28 postoperatively.
      CONCLUSION: In conclusion, AA attenuated the oxidative stress and inflammation
      response in the postoperative multifidus muscles, and remarkable differences were
      observed from the histological assessment and related marker genes expression.
      Our results provided important insight into the anti-inflammatory and anti
      oxidative effects of AA in the postoperative multifidus muscles. LEVEL OF
      EVIDENCE: N/A.

PMID- 29649093
TI  - Comparison of CYP3A4-Inducing Capacity of Enzyme-Inducing Antiepileptic Drugs
      Using 4beta-Hydroxycholesterol as Biomarker.
AB  - BACKGROUND: Enzyme-inducing antiepileptic drugs (EIAEDs) are among the clinically
      most important inducers of cytochrome P450 (CYP) 3A4, but there is limited
      evidence regarding the comparative potency of each EIAED in raising CYP3A4
      activity. The aim of this study was to estimate CYP3A4-inductive potency of
      EIAEDs by comparing CYP3A4 activity in patients treated with carbamazepine,
      phenobarbital, or phenytoin. METHODS: Residual serum samples from patients
      treated with EIAEDs or levetiracetam were collected from a therapeutic drug
      monitoring service for analysis of 4beta-hydroxycholesterol (4betaOHC), which is
      an indicator of CYP3A4 activity. The samples were collected between January and
      September 2016 at Diakonhjemmet Hospital, Oslo, Norway. Concentration of
      4betaOHC, EIAEDs, and levetiracetam was measured by ultra-performance liquid
      chromatography tandem mass spectrometry. Kruskal-Wallis and Mann-Whitney tests
      were used for comparison of 4betaOHC levels between the subgroups. RESULTS: In
      total, 4betaOHC measurements for 343 and 339 patients treated with EIAEDs and
      levetiracetam, respectively, were included in the study. Compared with
      levetiracetam-treated patients, the median 4betaOHC concentration was 3.3-fold,
      5.8-fold, and 6.9-fold higher in patients using phenobarbital, phenytoin, or
      carbamazepine, respectively (P < 0.0001). Phenytoin users (n = 65) and
      carbamazepine users (n = 225) had 1.8- and 2.1-fold higher median 4betaOHC
      concentration than phenobarbital users (n = 28), respectively (P <= 0.0001).
      CONCLUSIONS: This study shows that phenytoin and carbamazepine have approximately
      twice the CYP3A4-inducing potency of phenobarbital. The results indicate that 2
      fold higher doses of CYP3A4-metabolized drugs may generally be required during
      concurrent treatment with phenytoin or carbamazepine compared with phenobarbital.

PMID- 29649094
TI  - Methadone Maintenance Treatment: A 15-year Retrospective Study in Split-Dalmatia
      County, Croatia.
AB  - BACKGROUND: The aim of this retrospective study is to use existing
      epidemiological data on patients in methadone maintenance treatment in Split
      Dalmatia County from 2001 to 2015 to evaluate the substitution treatment system
      and policy of opiate addicts treatment, the epidemiological trend, and risk of
      overdose mortality. In addition, we would like to highlight the problem of poor
      control of methadone therapy and thus the possibility of selling methadone. The
      result is a greater number of deaths caused by methadone in people who were not
      in methadone therapy. METHODS: The research included data collected from 3189
      patients who had been in the drug abuse treatment program in Split-Dalmatia
      County during 2001-2015 and data gathered from autopsy examinations of patients
      in Split-Dalmatia County with emphasis on data for 186 overdosed patients during
      research period. RESULTS: The total number of patients in the methadone treatment
      program in Split-Dalmatia County during the research period, except in 2005 and
      2006, has been stable, while the number of new opiate patients, being in first
      time treatment, decreased by 62.5%. The number of addicts who were in a long-term
      maintenance program has increased by 198%, whereas the number of addicts who were
      in a short-term detoxification treatment has decreased by 96.4%. According to
      results obtained from performed autopsies, 186 death cases were determined as
      overdoses. Methadone was found in 56 of those cases and was declared as the cause
      of death in 39 cases (70%). Of the total number of autopsied patients with
      diagnosed methadone overdose, only 23 (59%) had been recorded to receive
      methadone therapy in Public Health Institute of Split-Dalmatia County database.
      CONCLUSIONS: The results of this study show the favorable epidemiological trend
      because of the decreasing number of new opiate patients in treatment. The
      retention of opiate patients in substitution therapy indicates the effectiveness
      of methadone maintenance programs. Our research did not determine any influence
      of methadone substitution therapy on an increasing risk of specific (overdose)
      mortality.

PMID- 29649095
TI  - Measuring Quality Gaps in TB Screening in South Africa Using Standardised Patient
      Analysis.
AB  - This is the first multi-district Standardised Patient (SP) study in South Africa.
      It measures the quality of TB screening at primary healthcare (PHC) facilities.
      We hypothesise that TB screening protocols and best practices are poorly adhered
      to at the PHC level. The SP method allows researchers to observe how healthcare
      providers identify, test and advise presumptive TB patients, and whether this
      aligns with clinical protocols and best practice. The study was conducted at PHC
      facilities in two provinces and 143 interactions at 39 facilities were analysed.
      Only 43% of interactions resulted in SPs receiving a TB sputum test and being
      offered an HIV test. TB sputum tests were conducted routinely (84%) while HIV
      tests were offered less frequently (47%). Nurses frequently neglected to ask SPs
      whether their household contacts had confirmed TB (54%). Antibiotics were
      prescribed without taking temperatures in 8% of cases. The importance of
      returning to the facility to receive TB test results was only explained in 28%.
      The SP method has highlighted gaps in clinical practice, signalling missed
      opportunities. Early detection of sub-optimal TB care is instrumental in
      decreasing TB-related morbidity and mortality. The findings provide the rationale
      for further quality improvement work in TB management.

PMID- 29649096
TI  - Defining Driver DNA Methylation Changes in Human Cancer.
AB  - Human malignant tumors are characterized by pervasive changes in the patterns of
      DNA methylation. These changes include a globally hypomethylated tumor cell
      genome and the focal hypermethylation of numerous 5'-cytosine-phosphate-guanine
      3' (CpG) islands, many of them associated with gene promoters. It has been
      challenging to link specific DNA methylation changes with tumorigenesis in a
      cause-and-effect relationship. Some evidence suggests that cancer-associated DNA
      hypomethylation may increase genomic instability. Promoter hypermethylation
      events can lead to silencing of genes functioning in pathways reflecting
      hallmarks of cancer, including DNA repair, cell cycle regulation, promotion of
      apoptosis or control of key tumor-relevant signaling networks. A convincing
      argument for a tumor-driving role of DNA methylation can be made when the same
      genes are also frequently mutated in cancer. Many of the most commonly
      hypermethylated genes encode developmental transcription factors, the methylation
      of which may lead to permanent gene silencing. Inactivation of such genes will
      deprive the cells in which the tumor may initiate from the option of undergoing
      or maintaining lineage differentiation and will lock them into a perpetuated stem
      cell-like state thus providing an additional window for cell transformation.

PMID- 29649097
TI  - Centrosome Positioning in Dictyostelium: Moving beyond Microtubule Tip Dynamics.
AB  - The variability in centrosome size, shape, and activity among different organisms
      provides an opportunity to understand both conserved and specialized actions of
      this intriguing organelle. Centrosomes in the model organism Dictyostelium sp.
      share some features with fungal systems and some with vertebrate cell lines and
      thus provide a particularly useful context to study their dynamics. We discuss
      two aspects, centrosome positioning in cells and their interactions with nuclei
      during division as a means to highlight evolutionary modifications to machinery
      that provide the most basic of cellular services.

PMID- 29649098
TI  - Three New Polyynes from Codonopsis pilosula and Their Activities on Lipid
      Metabolism.
AB  - Three new polyynes, named choushenpilosulynes A-C (1-3), were isolated from an
      85% aqueous EtOH extract of the roots of Codonopsis pilosula cultivated in
      Xundian County of Yunnan province, China. Their structures, including the
      absolute configuration of the glucose residue in 1 and 2, were determined by
      spectroscopic analysis and gas chromatography (GC). In addition, biological
      evaluation shows that all the compounds can inhibit the expression of the
      squalene monooxygenase (SQLE) gene in HepG2 cells, suggesting that these
      compounds may be involved in lipid metabolism.

PMID- 29649099
TI  - Functional and Radiological Results of Proximal Femoral Nail Antirotation (PFNA)
      Osteosynthesis in the Treatment of Unstable Pertrochanteric Fractures.
AB  - Pertrochanteric femur fractures are considered amongst the most commonly
      encountered fractures in the geriatric age group. We evaluated radiographic and
      functional outcomes of patients with unstable pertrochanteric fractures treated
      with the proximal femur nail antirotation (PFNA). Between March 2013 and December
      2015, fifty patients (28 male and 22 females with a mean age of 72.8 years
      (range, 20-94)) with unstable pertrochanteric fractures (AO 31.A2 and 31.A3) were
      fixed with the PFNA at our institution, and they were retrospectively evaluated.
      Forty one patients were treated with short PFNA and nine with long PFNA.
      Operative time ranged between 30 and 150 (average 73.60) min, blood loss ranged
      between 50 and 250 (average 80) milliliter and hospital stay ranged between 3 and
      18 (6.86) days. The mean follow-up period was 18 months (range, 11-31). At final
      follow-up, solid union of all fractures had been achieved without any implant
      related complications, the mean Harris Hip Score (HHS) was 79.34 +/- 9.10 points
      and the mean neck-shaft angle was 127.2 degrees  +/- 5.07 degrees . No
      significant differences were encountered between the functional and radiographic
      outcomes of the PFNA with regards to the AO fracture classification and the
      implant version. PFNA is a recommended option for the treatment of unstable
      pertrochanteric fractures owing to its easy insertion, reduced blood loss, stable
      fixation and satisfactory functional and radiological outcomes.

PMID- 29649100
TI  - Targeting the Adenosinergic Axis in Chronic Lymphocytic Leukemia: A Way to
      Disrupt the Tumor Niche?
AB  - Targeting adenosine triphosphate (ATP) metabolism and adenosinergic signaling in
      cancer is gaining momentum, as increasing evidence is showing their relevance in
      tumor immunology and biology. Chronic lymphocytic leukemia (CLL) results from the
      expansion of a population of mature B cells that progressively occupies the bone
      marrow (BM), the blood, and peripheral lymphoid organs. Notwithstanding
      significant progress in the treatment of these patients, the cure remains an
      unmet clinical need, suggesting that novel drugs or drug combinations are needed.
      A unique feature of CLL is its reliance on micro-environmental signals for
      proliferation and cell survival. We and others have shown that the lymphoid
      niche, an area of intense interactions between leukemic and bystander non-tumor
      cells, is a typically hypoxic environment. Here adenosine is generated by
      leukemic cells, as well as by cells of myeloid origin, acting through autocrine
      and paracrine mechanisms, ultimately affecting tumor growth, limiting drug
      responses, and skewing the immune cells towards a tolerant phenotype. Hence,
      understanding the mechanisms through which this complex network of enzymes,
      receptors, and metabolites functions in CLL, will pave the way to the use of
      pharmacological agents targeting the system, which, in combination with drugs
      targeting leukemic cells, may get us one step closer to curing these patients.

PMID- 29649102
TI  - Development of a Waterproof Crack-Based Stretchable Strain Sensor Based on PDMS
      Shielding.
AB  - This paper details the design of a poly(dimethylsiloxane) (PDMS)-shielded
      waterproof crack-based stretchable strain sensor, in which the electrical
      characteristics and sensing performance are not influenced by changes in
      humidity. This results in a higher number of potential applications for the
      sensor. A previously developed omni-purpose stretchable strain (OPSS) sensor was
      used as the basis for this work, which utilizes a metal cracking structure and
      provides a wide sensing range and high sensitivity. Changes in the conductivity
      of the OPSS sensor, based on humidity conditions, were investigated along with
      the potential possibility of using the design as a humidity sensor. However, to
      prevent conductivity variation, which can decrease the reliability and sensing
      ability of the OPSS sensor, PDMS was utilized as a shielding layer over the OPSS
      sensor. The PDMS-shielded OPSS sensor showed approximately the same electrical
      characteristics as previous designs, including in a high humidity environment,
      while maintaining its strain sensing capabilities. The developed sensor shows
      promise for use under high humidity conditions and in underwater applications.
      Therefore, considering its unique features and reliable sensing performance, the
      developed PDMS-shielded waterproof OPSS sensor has potential utility in a wide
      range of applications, such as motion monitoring, medical robotics and wearable
      healthcare devices.

PMID- 29649101
TI  - Pathobiologic Roles of Epstein-Barr Virus-Encoded MicroRNAs in Human Lymphomas.
AB  - Epstein-Barr virus (EBV) is a human gamma-herpesvirus implicated in several human
      malignancies, including a wide range of lymphomas. Several molecules encoded by
      EBV in its latent state are believed to be related to EBV-induced
      lymphomagenesis, among which microRNAs-small RNAs with a posttranscriptional
      regulating role-are of great importance. The genome of EBV encodes 44 mature
      microRNAs belonging to two different classes, including BamHI-A rightward
      transcript (BART) and Bam HI fragment H rightward open reading frame 1 (BHRF1),
      with different expression levels in different EBV latency types. These microRNAs
      might contribute to the pathogenetic effects exerted by EBV through targeting
      self mRNAs and host mRNAs and interfering with several important cellular
      mechanisms such as immunosurveillance, cell proliferation, and apoptosis. In
      addition, EBV microRNAs can regulate the surrounding microenvironment of the
      infected cells through exosomal transportation. Moreover, these small molecules
      could be potentially used as molecular markers. In this review, we try to present
      an updated and extensive view of the role of EBV-encoded miRNAs in human
      lymphomas.

PMID- 29649103
TI  - The Anti-Periodontitis Effects of Ethanol Extract Prepared Using Lactobacillus
      paracasei subsp. paracasei NTU 101.
AB  - Poor oral health and related diseases, including caries, periodontal disease, and
      oral cancer, are highly prevalent across the world, particularly in the elderly.
      This study aimed to investigate the anti-periodontitis activity of fermented skim
      milk produced using the promising probiotic Lactobacillus paracasei subsp.
      paracasei NTU 101 (NTU101FM). An initial analysis found that an ethanol extract
      of NTU101FM displayed anti-oxidative activities. Further investigation of
      pathogen growth inhibition zones, minimum inhibitory concentrations (MICs), and
      minimum bactericidal concentrations (MBCs) revealed that the NTU101FM ethanol
      extract also had anti-periodontal pathogen activities. In addition, the NTU101FM
      ethanol extract significantly decreased the release of pro-inflammatory cytokines
      induced by lipopolysaccharide (LPS) in RAW 264.7 macrophage cells. Finally, the
      NTU101FM ethanol extract was found to inhibit receptor activator of nuclear
      factor-kappaB ligand (RANKL)-induced osteoclast differentiation by reducing
      tartrate-resistant acid phosphatase (TRAP) activity and the number of TRAP
      positive multinucleated osteoclasts. In summary, our study demonstrated that
      ethanol extract prepared from NTU101FM has potential use as an anti-periodontitis
      agent.

PMID- 29649104
TI  - Coordination of GPR40 and Ketogenesis Signaling by Medium Chain Fatty Acids
      Regulates Beta Cell Function.
AB  - Diabetes prevalence increases with age, and beta-cell dysfunction contributes to
      the incidence of the disease. Dietary lipids have been recognized as contributory
      factors in the development and progression of the disease. Unlike long chain
      triglycerides, medium chain triglycerides (MCT) increase fat burning in animal
      and human subjects as well as serum C-peptide in type 2 diabetes patients. We
      evaluated the beneficial effects of MCT on beta-cells in vivo and in vitro. MCT
      improved glycemia in aged rats via beta-cell function assessed by measuring
      insulin secretion and content. In beta-cells, medium chain fatty acid (MCFA)-C10
      activated fatty acid receptor 1 FFAR1/GPR40, while MCFA-C8 induced mitochondrial
      ketogenesis and the C8:C10 mixture improved beta cell function. We showed that
      GPR40 signaling positively impacts ketone body production in beta-cells, and
      chronic treatment with beta-hydroxybutyrate (BHB) improves beta-cell function. We
      also showed that BHB and MCFA help beta-cells recover from lipotoxic stress by
      improving mitochondrial function and increasing the expression of genes involved
      in beta-cell function and insulin biogenesis, such as Glut2, MafA, and NeuroD1 in
      primary human islets. MCFA offers a therapeutic advantage in the preservation of
      beta-cell function as part of a preventative strategy against diabetes in at risk
      populations.

PMID- 29649105
TI  - Glyteer, Soybean Tar, Impairs IL-4/Stat6 Signaling in Murine Bone Marrow-Derived
      Dendritic Cells: The Basis of Its Therapeutic Effect on Atopic Dermatitis.
AB  - Atopic dermatitis (AD) is a common inflammatory skin disease. Recent studies have
      revealed the involvement of T helper (Th)2 cytokines including Interleukin 4 (IL
      4) in the pathogenesis of AD. Since epidermal Langerhans cells (LCs) and dermal
      myeloid dendritic cells (DCs) produce CCL17 and CCL22 that chemoattract Th2
      cells, interfering with CCL17 and CCL22 production from LCs and dermal myeloid
      DCs may be beneficial in the treatment of AD. To investigate this, we stimulated
      murine bone marrow-derived DCs (BMDCs) with IL-4. IL-4 stimulation produced Ccl17
      and Ccl22, which was attenuated by soybean tar Glyteer, a known aryl hydrocarbon
      receptor (Ahr) activator. Notably, Glyteer treatment blocked the nuclear
      translocation of Stat6 induced by IL-4 stimulation, suggesting that this
      treatment impairs the IL-4/Stat6 signaling pathway in BMDCs. Unexpectedly,
      Glyteer treatment did not potently upregulate the expression of Cyp1a1, a
      specific Ahr-responsive gene, suggesting that its inhibitory machinery for Ccl17
      and Ccl22 expression is likely to operate in an Ahr-independent manner. These
      findings indicate that Glyteer may exhibit therapeutic potential for AD by
      downregulating the CCL17 and CCL22 production from DCs in a Th2-deviated
      microenvironment.

PMID- 29649106
TI  - MOSH Syndrome (Male Obesity Secondary Hypogonadism): Clinical Assessment and
      Possible Therapeutic Approaches.
AB  - Male obesity secondary hypogonadism (MOSH) impairs fertility, sexual function,
      bone mineralization, fat metabolism, cognitive function, deteriorates muscle mass
      and alters body composition. The aim of this pilot study was to evaluate the
      effect of dietary intervention and physical activity on the MOSH patient's
      hormonal profile after a 10% weight loss compared to baseline. Fourteen male
      patients were enrolled. Hormonal, lipid, glycemic profiles and body composition
      were determined at baseline and after a 10% weight loss. Aging Male Symptoms
      Scale (AMS) and Yale Food Addiction Scale (YFAS) were administered to patients in
      order to investigate hypogonadal symptoms and food addiction. Compared to
      baseline, a significant increase of Total Testosterone (TT) (300.2 +/- 79.5 ng/dL
      vs. 408.3 +/- 125.9 ng/dL, p = 0.002, 95% CI 26.8; 167.7) and a reduction of 17
      Beta Estradiol level (48.3 +/- 14.9 pg/mL vs. 39.2 +/- 15.2 pg/mL, p = 0.049, 95%
      CI 3.1; 0.0) were observed. Total Fat Mass (FM) percentage, android and gynoid
      fat mass percentage (39.2 +/- 6.4% vs. 36.2 +/- 5.8%, p = 0.0001, 95% CI 22.5;
      62.3; 51.5 +/- 6.8% vs. 47.6 +/- 6.8%, p = 0.001, 95% CI 0.6; 1.8, vs. 39.2 +/-
      6.2% vs. 36.5 +/- 6.3% p = 0.0001, 95% CI 0.9; 2.0 respectively) were
      significantly decreased after nutritional intervention. In addition, total Fat
      Free Mass (FFM) in kg was significantly reduced after 10% weight loss (62.3 +/-
      2.8 kg vs. 60.3 +/- 7.7 kg, p = 0.002, 95% CI 45.0; 93.0). Lifestyle changes,
      specifically dietotherapy and physical activity, induce positive effects on
      hypogonadism due to obesity.

PMID- 29649107
TI  - Impaired Hematologic Status in Relation to Clinical Outcomes among HIV-Infected
      Adults from Uganda: A Prospective Cohort Study.
AB  - Impaired hematologic status (IHS) was investigated as a determinant of immune
      function defined as cluster of differentiation 4 (CD4) T-helper cell count,
      quality of life (QOL) weight and hospitalization/mortality over 18-months among
      398 adult persons living with HIV/AIDS (PLWHA) on anti-retroviral therapy. IHS
      was defined as having anemia at baseline (Hemoglobin: <12 g/dL for women and <13
      g/dL for men), time-updated anemia or having low (<30 MUg/L) or high (>200 MUg/L
      for men and >150 MUg/L for women) ferritin levels at baseline. Months-to
      hospitalization/death or study-end (if no event) was calculated from enrollment.
      Multivariable linear-mixed models quantified associations between IHS and changes
      in CD4 cell-count, weight gain and QOL. Cox proportional hazards models
      calculated hazard ratios (HR) and corresponding 95% confidence intervals (CI) for
      IHS-related differences in time-to-hospitalization/death. The prevalences of
      anemia and high and low ferritin levels at baseline were 48.7% (n = 194), 40.5%
      (n = 161) and 17% (n = 68), respectively. Most patients (63.4%, n = 123) remained
      anemic during follow-up. Weight gained (ferritin-time interaction, p < 0.01) and
      QOL (anemia-time interaction, p = 0.05; ferritin-time interaction, p = 0.01) were
      lower for PLWHA with versus without IHS. Relative to anemia-free/normal ferritin,
      the risk of hospitalization/death was elevated for PLWHA with anemia (HR = 2.0;
      95% CI: 1.2-3.6), low or high ferritin (HR: 1.8-1.9, 95% CI: 0.9-4.1) and those
      that developed new/persistent/progressive anemia (HR: 2.3-6.7, 95% CI: 1.0-12.7).
      Among PLWHA, IHS predicted deficits in QOL, low weight gain and a high risk of
      hospitalization/death. Intervention to mitigate persistent IHS may be warranted
      among PLWHA on long-term highly active antiretroviral therapy (HAART) to improve
      health outcomes.

PMID- 29649108
TI  - Postnatal Growth Disadvantage of the Small for Gestational Age Preterm Twins.
AB  - In this study, we examined early growth characteristics among small-for
      gestational-age (SGA) preterm twins compared to their appropriate-for-gestational
      age (AGA) counterparts. A retrospective study evaluated all consecutive twins
      born between 2008 and 2015 at a tertiary referral center whose gestational age
      ranged from 30.0 to 34.86 weeks. Included were twins in which one twin was AGA
      and the other SGA at birth. Changes of >=2, 1-1.99, and 0-0.99 in z-score between
      births and 36 weeks post menstrual age (PMA) were respectively defined as severe,
      moderate, and mild postnatal growth failure (PNGF) in weight or head
      circumference (HC). Early neonatal morbidities were documented. Multiple logistic
      regression analysis was applied to determine conditions associated with PNGF and
      its severity. Out of 666 sets of twins, 83 met the inclusion criteria. Weight
      PNGF was similar and mild among the SGA and the AGA groups (0.9 +/- 0.46 vs. 0.96
      +/- 0.44 z-score, respectively, p = 0.24). At 36 weeks PMA, a significantly
      larger proportion of SGAs were below -2 z-scores in weight (84.3%) compared to
      birth (31.3%) or to the AGAs (8.4%). In both groups, weight PNGF correlated with
      the time needed to regain birth weight. HC PNGF was mild among both groups, yet
      significantly more prominent among the AGAs (0.39 +/- 0.72 z-score) vs. SGAs
      (0.75 +/- 0.65 z-score, p = 0.001). We suggest that among preterm SGA infants,
      the absolute z-score should be used to assess the severity of weight PNGF.
      Individual nutritional strategies to decrease time to regain birth weight may
      mitigate severe malnutrition among SGAs.

PMID- 29649110
TI  - Luminescence Mechanism of Carbon Dots by Tailoring Functional Groups for Sensing
      Fe3+ Ions.
AB  - In this paper, spherical carbon dots (CDs) with distinct compositions and surface
      states have been successfully synthesized by a facile microwave method. From the
      fluorescence spectra, several characteristic luminescence features have been
      observed: surface amino groups are dominant in the whole emission spectra
      centering at 445 nm, and the fingerprint emissions relevant to the impurity
      levels formed by some groups related to C and N elements, including C-C/C=C
      (intrinsic C), C-N (graphitic N), N-containing heterocycles (pyridine N) and C=O
      groups, are located around 305 nm, 355 nm, 410 nm, and 500 nm, respectively.
      Those fine luminescence features could be ascribed to the electron transition
      among various trapping states within the band structure caused by different
      chemical bonds in carbon cores, or functional groups attached to the CDs'
      surfaces. According to the theoretical calculations and experimental results, a
      scheme of the band structure has been proposed to describe the positions of those
      trapping states within the band gap. Additionally, it has also been observed that
      the emission of CDs is sensitive to the concentration of Fe3+ ions with a linear
      relation in the range of Fe3+ concentration from 12.5 to 250 MUM.

PMID- 29649109
TI  - MicroRNA Expression Analysis of In Vitro Dedifferentiated Human Pancreatic Islet
      Cells Reveals the Activation of the Pluripotency-Related MicroRNA Cluster miR
      302s.
AB  - beta-cell dedifferentiation has been recently suggested as an additional
      mechanism contributing to type-1 and to type-2 diabetes pathogenesis. Moreover,
      several studies demonstrated that in vitro culture of native human pancreatic
      islets derived from non-diabetic donors resulted in the generation of an
      undifferentiated cell population. Additional evidence from in vitro human beta
      cell lineage tracing experiments, demonstrated that dedifferentiated cells derive
      from beta-cells, thus representing a potential in vitro model of beta-cell
      dedifferentiation. Here, we report the microRNA expression profiles analysis of
      in vitro dedifferentiated islet cells in comparison to mature human native
      pancreatic islets. We identified 13 microRNAs upregulated and 110 downregulated
      in islet cells upon in vitro dedifferentiation. Interestingly, among upregulated
      microRNAs, we observed the activation of microRNA miR-302s cluster, previously
      defined as pluripotency-associated. Bioinformatic analysis indicated that miR
      302s are predicted to target several genes involved in the control of beta
      cell/epithelial phenotype maintenance; accordingly, such genes were downregulated
      upon human islet in vitro dedifferentiation. Moreover, we uncovered that cell
      cell contacts are needed to maintain low/null expression levels of miR-302. In
      conclusion, we showed that miR-302 microRNA cluster genes are involved in in
      vitro dedifferentiation of human pancreatic islet cells and inhibits the
      expression of multiple genes involved in the maintenance of beta-cell mature
      phenotype.

PMID- 29649111
TI  - Microbial Groundwater Quality Status of Hand-Dug Wells and Boreholes in the
      Dodowa Area of Ghana.
AB  - To assess the suitability of water sources for drinking purposes, samples were
      taken from groundwater sources (boreholes and hand-dug wells) used for drinking
      water in the Dodowa area of Ghana. The samples were analyzed for the presence of
      fecal indicator bacteria (Escherichia coli) and viruses (Adenovirus and
      Rotavirus), using membrane filtration with plating and glass wool filtration with
      quantitative polymerase chain reaction (PCR), respectively. In addition, sanitary
      inspection of surroundings of the sources was conducted to identify their
      vulnerability to pollution. The presence of viruses was also assessed in water
      samples from the Dodowa River. More than 70% of the hand-dug wells were sited
      within 10 m of nearby sources of contamination. All sources contained E. coli
      bacteria, and their numbers in samples of water between dug wells and boreholes
      showed no significant difference (p = 0.48). Quantitative PCR results for
      Adenovirus indicated 27% and 55% were positive for the boreholes and hand-dug
      wells, respectively. Samples from all boreholes tested negative for the presence
      of Rotavirus while 27% of the dug wells were positive for Rotavirus. PCR tests of
      20% of groundwater samples were inhibited. Based on these results we concluded
      that there is systemic microbial and fecal contamination of groundwater in the
      area. On-site sanitation facilities, e.g., pit latrines and unlined wastewater
      drains, are likely the most common sources of fecal contamination of groundwater
      in the area. Water abstracted from groundwater sources needs to be treated before
      use for consumption purposes. In addition, efforts should be made to delineate
      protected areas around groundwater abstraction points to minimize contamination
      from point sources of pollution.

PMID- 29649112
TI  - Effects of BTEX on the Removal of Acetone in a Coaxial Non-Thermal Plasma
      Reactor: Role Analysis of the Methyl Group.
AB  - The removal of acetone and benzene series (BTEX) under individual and concurrent
      conditions is carried out in a coaxial nonthermal plasma (NTP) reactor. The
      results show that the benzene series has a significant negative impact on acetone
      conversion and CO2 selectivity under NTP treatment. Furthermore, it is found that
      p-xylene significantly promotes COx selectivity under co-treatment with acetone
      because of greater CO generation. Based on the results of transient FTIR, MS, and
      GC-MS, it is seen that quantities of formic acid, formaldehyde, and ring-opening
      byproducts from benzene series decomposition are reduced, while quantities of
      aromatic byproducts with carboxyl, phenolic, and aldehyde groups on the benzene
      ring increase under coexistence conditions. With the help of theoretical
      calculation and kinetic analysis, hydrogen abstraction from the methyl group and
      active hydroxyl radical consumption are proposed as critical factors in the BTEX
      inhibition effect on acetone degradation.

PMID- 29649114
TI  - Optimized Multi-Spectral Filter Array Based Imaging of Natural Scenes.
AB  - Multi-spectral imaging using a camera with more than three channels is an
      efficient method to acquire and reconstruct spectral data and is used extensively
      in tasks like object recognition, relighted rendering, and color constancy.
      Recently developed methods are used to only guide content-dependent filter
      selection where the set of spectral reflectances to be recovered are known a
      priori. We present the first content-independent spectral imaging pipeline that
      allows optimal selection of multiple channels. We also present algorithms for
      optimal placement of the channels in the color filter array yielding an efficient
      demosaicing order resulting in accurate spectral recovery of natural reflectance
      functions. These reflectance functions have the property that their power
      spectrum statistically exhibits a power-law behavior. Using this property, we
      propose power-law based error descriptors that are minimized to optimize the
      imaging pipeline. We extensively verify our models and optimizations using large
      sets of commercially available wide-band filters to demonstrate the greater
      accuracy and efficiency of our multi-spectral imaging pipeline over existing
      methods.

PMID- 29649113
TI  - New and Old Genes Associated with Primary and Established Responses to Paclitaxel
      Treatment in Ovarian Cancer Cell Lines.
AB  - Development of drug resistance is the main reason for low chemotherapy
      effectiveness in treating ovarian cancer. Paclitaxel (PAC) is a chemotherapeutic
      drug used in the treatment of this cancer. We analysed the development of PAC
      resistance in two ovarian cancer cell lines. Exposure of drug-sensitive cell
      lines (A2780 and W1) to PAC was used to determine the primary response. An
      established response was determined in PAC-resistant sublines of the A2780 and W1
      cell lines. qRT-PCR was performed to measure the expression levels of specific
      genes. We observed decreased expression of the PCDH9, NSBP1, MCTP1 and SEMA3A
      genes in the PAC-resistant cell lines. Short-term exposure to PAC led to
      increased expression of the MDR1 and BCRP genes in the A2780 and W1 cell lines.
      In the A2780 cell line, we also observed increased expression of the C4orf18 gene
      and decreased expression of the PCDH9 and SEMA3A genes after PAC treatment. In
      the W1 cell line, short-term treatment with PAC upregulated the expression of the
      ALDH1A1 gene, a marker of Cancer stem cells (CSCs). Our results suggest that
      downregulation of the PCDH9, NSBP1, MCTP1 and SEMA3A genes and upregulation of
      the MDR1, BCRP, C4orf18 and ALDH1A1 genes may be related to PAC resistance.

PMID- 29649115
TI  - Public Health Care Financing and the Costs of Cancer Care: A Cross-National
      Analysis.
AB  - Expenditure and financing aspects in the healthcare system in general, and in
      cancer care in particular, are subjects of increasing concern to the medical
      community. Nowadays, it is imperative for the healthcare system to respond to the
      challenge of universal access to quality healthcare, by measuring the financial
      resources within the healthcare sector. The purpose of this review is to
      highlight the major gaps in the healthcare expenditures for all types of care, as
      well as on cancer and anti-cancer drugs across 28 European Union member states.
      The indicators taken into account are divided into two major groups: (1)
      healthcare expenditures for all types of care, and (2) healthcare expenditures on
      cancer and anti-cancer drugs. The programs used for our analysis are SPSS
      Statistics V20.0 (IBM Corporation, Armonk, NY, USA) and Stat World Explorer. The
      overall picture confirms that there are considerable disparities between the 28
      countries in relation to their expenditures on health. The trend in public
      expenditures for all types of care, compared to the share of healthcare
      expenditures as a percentage of the GDP, shows the increase of health expenses
      between 2010 and 2014, but a lower rise compared to the total GDP increase.
      Healthcare expenditure on cancer (%THE) is rather low, despite the high cost
      associated with anti-cancer drugs. New treatments and drugs development will be
      increasingly difficult to achieve if the share devoted to cancer does not
      increase, and the lack of funds may act as a barrier in receiving high-quality
      care.

PMID- 29649116
TI  - Mechanical Grinding Preparation and Characterization of TiO2-Coated Wollastonite
      Composite Pigments.
AB  - TiO2-coated wollastonite composite pigments were prepared by the mechano-chemical
      grinding of wollastonite and TiO2 powder together in a wet ultrafine stirred
      mill. X-ray diffraction, scanning electron microscopy, X-ray photoelectron
      spectroscopy and infrared spectra were used to investigate the microstructures
      and morphologies of the composite and the reaction mechanism. The results
      indicate that the TiO2-coated wollastonite composite pigments have similar
      properties to titanium dioxide pigment, showing much better properties than dry
      and wet mixing of wollastonite and TiO2. The hiding power of TiO2-coated
      wollastonite composite pigments (45% TiO2) is 17.97 g/m2, reaching 81.08% of
      titanium dioxide. A firm combination between wollastonite and TiO2 is obtained
      through a surface dehydroxylation reaction during the mechano-chemical method.

PMID- 29649117
TI  - The Effect of Weld Reinforcement and Post-Welding Cooling Cycles on Fatigue
      Strength of Butt-Welded Joints under Cyclic Tensile Loading.
AB  - This research deals with the fatigue behavior of butt-welded joints, by
      considering the geometry and post-welding cooling cycles, as a result of cooling
      in quiet air and immersed in water. ASTM A-36 HR structural steel was used as the
      base metal for the shielded metal arc welding (SMAW) process with welding
      electrode E6013. The welding reinforcement was 1 mm and 3 mm, respectively; axial
      fatigue tests were carried out to determine the life and behavior in cracks
      propagation of the tested welded joints, mechanical characterization tests of
      properties in welded joints such as microhardness, Charpy impact test and
      metallographic analysis were carried out. The latter were used as input for the
      analysis by finite elements which influence the initiation and propagation of
      cracks and the evaluation of stress intensity factors (SIF). The latter led to
      obtaining the crack propagation rate and the geometric factor. The tested
      specimens were analyzed, by taking photographs of the cracks at its beginning in
      order to make a count of the marks at the origin of the crack. From the results
      obtained and the marks count, the fatigue crack growth rate and the influence of
      the cooling media on the life of the welded joint are validated, according to the
      experimental results. It can be concluded that the welded joints with a higher
      weld reinforcement have a shorter fatigue life. This is due to the stress
      concentration that occurs in the vicinity of the weld toe.

PMID- 29649118
TI  - Optical DNA Biosensor Based on Square-Planar Ethyl Piperidine Substituted
      Nickel(II) Salphen Complex for Dengue Virus Detection.
AB  - A sensitive and selective optical DNA biosensor was developed for dengue virus
      detection based on novel square-planar piperidine side chain-functionalized N,N'
      bis-4-(hydroxysalicylidene)-phenylenediamine-nickel(II), which was able to
      intercalate via nucleobase stacking within DNA and be functionalized as an
      optical DNA hybridization marker. 3-Aminopropyltriethoxysilane (APTS)-modified
      porous silica nanospheres (PSiNs), was synthesized with a facile mini-emulsion
      method to act as a high capacity DNA carrier matrix. The Schiff base salphen
      complexes-labelled probe to target nucleic acid on the PSiNs renders a colour
      change of the DNA biosensor to a yellow background colour, which could be
      quantified via a reflectance transduction method. The reflectometric DNA
      biosensor demonstrated a wide linear response range to target DNA over the
      concentration range of 1.0 * 10-16-1.0 * 10-10 M (R2 = 0.9879) with an ultralow
      limit of detection (LOD) at 0.2 aM. The optical DNA biosensor response was stable
      and maintainable at 92.8% of its initial response for up to seven days of storage
      duration with a response time of 90 min. The reflectance DNA biosensor obtained
      promising recovery values of close to 100% for the detection of spiked synthetic
      dengue virus serotypes 2 (DENV-2) DNA concentration in non-invasive human
      samples, indicating the high accuracy of the proposed DNA analytical method for
      early diagnosis of all potential infectious diseases or pathological genotypes.

PMID- 29649119
TI  - Crystal Structure of Botulinum Neurotoxin A2 in Complex with the Human Protein
      Receptor SV2C Reveals Plasticity in Receptor Binding.
AB  - Botulinum neurotoxins (BoNTs) are a family of highly dangerous bacterial toxins,
      with seven major serotypes (BoNT/A-G). Members of BoNTs, BoNT/A1 and BoNT/B1,
      have been utilized to treat an increasing number of medical conditions. The
      clinical trials are ongoing for BoNT/A2, another subtype of BoNT/A, which showed
      promising therapeutic properties. Both BoNT/A1 and BoNT/A2 utilize three isoforms
      of synaptic vesicle protein SV2 (SV2A, B, and C) as their protein receptors. We
      here present a high resolution (2.0 A) co-crystal structure of the BoNT/A2
      receptor-binding domain in complex with the human SV2C luminal domain. The
      structure is similar to previously reported BoNT/A-SV2C complexes, but a shift of
      the receptor-binding segment in BoNT/A2 rotates SV2C in two dimensions giving
      insight into the dynamic behavior of the interaction. Small differences in key
      residues at the binding interface may influence the binding to different SV2
      isoforms, which may contribute to the differences between BoNT/A1 and BoNT/A2
      observed in the clinic.

PMID- 29649120
TI  - What Is the Evidence for "Food Addiction?" A Systematic Review.
AB  - The diagnostic construct of "food addiction" is a highly controversial subject.
      The current systematic review is the first to evaluate empirical studies
      examining the construct of "food addiction" in humans and animals. Studies were
      included if they were quantitative, peer-reviewed, and in the English language.
      The 52 identified studies (35 articles) were qualitatively assessed to determine
      the extent to which their findings indicated the following addiction
      characteristics in relation to food: brain reward dysfunction, preoccupation,
      risky use, impaired control, tolerance/withdrawal, social impairment, chronicity,
      and relapse. Each pre-defined criterion was supported by at least one study.
      Brain reward dysfunction and impaired control were supported by the largest
      number of studies (n = 21 and n = 12, respectively); whereas risky use was
      supported by the fewest (n = 1). Overall, findings support food addiction as a
      unique construct consistent with criteria for other substance use disorder
      diagnoses. The evidence further suggests that certain foods, particularly
      processed foods with added sweeteners and fats, demonstrate the greatest
      addictive potential. Though both behavioral and substance-related factors are
      implicated in the addictive process, symptoms appear to better fit criteria for
      substance use disorder than behavioral addiction. Future research should explore
      social/role impairment, preoccupation, and risky use associated with food
      addiction and evaluate potential interventions for prevention and treatment.

PMID- 29649121
TI  - Synthesis of Hydroxyapatite, beta-Tricalcium Phosphate and Biphasic Calcium
      Phosphate Particles to Act as Local Delivery Carriers of Curcumin: Loading,
      Release and In Vitro Studies.
AB  - The successful synthesis of hydroxyapatite (HA), beta-Tricalcium phosphate (beta
      TCP) and two biphasic mixtures (BCPs) of the two was performed by means of wet
      precipitation. The resulting crystals were characterized and the BCP composition
      was analyzed and identified as 13% HA-87% TCP and 41% HA-59% TCP. All samples
      were treated with curcumin solutions, and the degree of curcumin loading and
      release was found to be proportional to the TCP content of the ceramic. No
      further cytotoxicity was observed upon MG-63 treatment with the curcumin-loaded
      ceramics. Finally, the alkaline phosphatase activity of the cells was found to
      increase with increasing content of TCP, which provides an encouraging proof of
      concept for the use of curcumin-loaded synthetic biomaterials in bone remodeling.

PMID- 29649122
TI  - Production and Characterization of an Extracellular Acid Protease from
      Thermophilic Brevibacillus sp. OA30 Isolated from an Algerian Hot Spring.
AB  - Proteases have numerous biotechnological applications and the bioprospection for
      newly-thermostable proteases from the great biodiversity of thermophilic
      microorganisms inhabiting hot environments, such as geothermal sources, aims to
      discover more effective enzymes for processes at higher temperatures. We report
      in this paper the production and the characterization of a purified acid protease
      from strain OA30, a moderate thermophilic bacterium isolated from an Algerian hot
      spring. Phenotypic and genotypic study of strain OA30 was followed by the
      production of the extracellular protease in a physiologically-optimized medium.
      Strain OA30 showed multiple extracellular proteolytic enzymes and protease 32-F38
      was purified by chromatographic methods and its biochemical characteristics were
      studied. Strain OA30 was affiliated with Brevibacillus thermoruber species.
      Protease 32-F38 had an estimated molecular weight of 64.6 kDa and was optimally
      active at 50  degrees C. It showed a great thermostability after 240 min and its
      optimum pH was 6.0. Protease 32-F38 was highly stable in the presence of
      different detergents and solvents and was inhibited by metalloprotease
      inhibitors. The results of this work suggest that protease 32-F38 might have
      interesting biotechnological applications.

PMID- 29649123
TI  - Phytochemical Properties and Nutrigenomic Implications of Yacon as a Potential
      Source of Prebiotic: Current Evidence and Future Directions.
AB  - The human gut is densely populated with diverse microbial communities that are
      essential to health. Prebiotics and fiber have been shown to possess the ability
      to modulate the gut microbiota. One of the plants being considered as a potential
      source of prebiotic is yacon. Yacon is an underutilized plant consumed as a
      traditional root-based fruit in South America. Yacon mainly contains
      fructooligosaccharides (FOS) and inulin. Therefore, it has bifidogenic benefits
      for gut health, because FOS are not easily broken down by digestive enzymes.
      Bioactive chemical compounds and extracts isolated from yacon have been studied
      for their various nutrigenomic properties, including as a prebiotic for
      intestinal health and their antimicrobial and antioxidant effects. This article
      reviewed scientific studies regarding the bioactive chemical compounds and
      nutrigenomic properties of extracts and isolated compounds from yacon. These
      findings may help in further research to investigate yacon-based nutritional
      products. Yacon can be considered a potential prebiotic source and a novel
      functional food. However, more detailed epidemiological, animal, and human
      clinical studies, particularly mechanism-based and phytopharmacological studies,
      are lacking for the development of evidence-based functional food products.

PMID- 29649124
TI  - Influence of Solvent Composition on the Performance of Spray-Dried Co-Amorphous
      Formulations.
AB  - Ball-milling is usually used to prepare co-amorphous drug-amino acid (AA)
      mixtures. In this study, co-amorphous drug-AA mixtures were produced using spray
      drying, a scalable industrially preferred preparation method. The influence of
      the solvent type and solvent composition was investigated. Mixtures of
      indomethacin (IND) and each of the three AAs arginine, histidine, and lysine were
      ball-milled and spray-dried at a 1:1 molar ratio, respectively. Spray-drying was
      performed at different solvent ratios in (a) ethanol and water mixtures and (b)
      acetone and water mixtures. Different ratios of these solvents were chosen to
      study the effect of solvent mixtures on co-amorphous formulation. Residual
      crystallinity, thermal properties, salt/partial salt formation, and powder
      dissolution profiles of the IND-AA mixtures were investigated and compared to
      pure crystalline and amorphous IND. It was found that using spray-drying as a
      preparation method, all IND-AA mixtures could be successfully converted into the
      respective co-amorphous forms, irrespective of the type of solvent used, but
      depending on the solvent mixture ratios. Both ball-milled and spray-dried co
      amorphous samples showed an enhanced dissolution rate and maintained
      supersaturation compared to the crystalline and amorphous IND itself. The spray
      dried samples resulting in co-amorphous samples were stable for at least seven
      months of storage.

PMID- 29649125
TI  - Bavachinin Induces Oxidative Damage in HepaRG Cells through p38/JNK MAPK
      Pathways.
AB  - Drug-induced liver injury is one of the main causes of drug non-approval and drug
      withdrawal by the Food and Drug Administration (FDA). Bavachinin (BVC) is a
      natural product derived from the fruit of the traditional Chinese herb Fructus
      Psoraleae (FP). There have been reports of acute liver injury following the
      administration of FP and its related proprietary medicines. To explore BVC
      hepatotoxicity and its mechanisms, we used the HepaRG cell line. In our recent
      research, we showed that BVC induces HepaRG cell death, mainly via BVC-induced
      oxidative damage. The formation of ROS is closely related to the activation of
      the stress-activated kinases, JNK and p38, while SP600125 (SP, JNK inhibitor) and
      SB203580 (SB, p38 inhibitor) pretreatment inhibited the generation of ROS. On the
      other hand, N-acetylcysteine (NAC) pretreatment prevented the phosphorylation of
      p38 but not that of JNK. Taken together, these data reveal that BVC induces
      HepaRG cell death via ROS and the JNK/p38 signaling pathways.

PMID- 29649126
TI  - Effects of Rural Medical Insurance on Chronically Ill Patients' Choice of the
      Same Hospital Again in Rural Northern China.
AB  - The emergence of rural health insurance plays a crucial role in alleviating the
      pressure on rural medical expenditure. Under the current medical system in
      northern China, rural medical insurance may reduce the free referral of patients
      with chronic diseases among hospitals. This study was carried out based on the
      results of an investigation of rural chronically-ill patients in eight county
      hospitals in northern China, as well as through the comparison and analysis of
      patients with chronic diseases, considering whether they were with or without
      rural health insurance. The main results showed that both age (chi2 = 22.9, p <
      0.000) and income level (chi2 = 18.5, p < 0.000) had considerable impact on the
      rural peoples' willingness to buy health insurance. Meanwhile, both the quality
      of the hospital's treatment (B = 0.555, p < 0.000), and service quality (B =
      0.168, p < 0.000) had a significant positive correlation with the likelihood of a
      given patient choosing the same hospital on the next visit, but the medical costs
      had a significant negative correlation (B = -0.137, p < 0.000). Eventually, it
      was found that the provision of rural health insurance had weakened the three
      relationships upon which the aforementioned correlations were based.

PMID- 29649127
TI  - Gene Therapy for Chronic HBV-Can We Eliminate cccDNA?
AB  - Chronic infection with the hepatitis B virus (HBV) is a global health concern and
      accounts for approximately 1 million deaths annually. Amongst other limitations
      of current anti-HBV treatment, failure to eliminate the viral covalently closed
      circular DNA (cccDNA) and emergence of resistance remain the most worrisome.
      Viral rebound from latent episomal cccDNA reservoirs occurs following cessation
      of therapy, patient non-compliance, or the development of escape mutants.
      Simultaneous viral co-infections, such as by HIV-1, further complicate
      therapeutic interventions. These challenges have prompted development of novel
      targeted hepatitis B therapies. Given the ease with which highly specific and
      potent nucleic acid therapeutics can be rationally designed, gene therapy has
      generated interest for antiviral application. Gene therapy strategies developed
      for HBV include gene silencing by harnessing RNA interference, transcriptional
      inhibition through epigenetic modification of target DNA, genome editing by
      designer nucleases, and immune modulation with cytokines. DNA-binding domains and
      effectors based on the zinc finger (ZF), transcription activator-like effector
      (TALE), and clustered regularly interspaced short palindromic repeat (CRISPR)
      systems are remarkably well suited to targeting episomal cccDNA. This review
      discusses recent developments and challenges facing the field of anti-HBV gene
      therapy, its potential curative significance and the progress towards clinical
      application.

PMID- 29649128
TI  - Vitamin D Deficiency and Antenatal and Postpartum Depression: A Systematic
      Review.
AB  - Vitamin D has been implicated in antenatal depression (AD) and postpartum
      depression (PPD) in many studies; however, results have been inconsistent due to
      the complexity of this association. We searched the MEDLINE, Embase, PsycINFO,
      and Maternity and Infant Care databases for literature addressing associations
      between vitamin D and AD and PPD. Two independent authors reviewed titles and
      abstracts of the search results and selected studies for full review. Data were
      extracted, and a quality rating was done using the Newcastle-Ottawa Scale (NOS)
      on the selected studies. A total of 239 studies were identified; 14 were included
      in the review. The quality assessment of the included studies ranged from
      moderate to high. Of the studies on PPD, five of nine (55%) showed a significant
      association between vitamin D and PPD. Five of seven (71%) studies on AD showed a
      significant association with vitamin D status. As the included studies used
      different effect estimates and statistical analyses to report the association, it
      was not possible to transform the existing data into one single effect measure to
      employ meta-analytic techniques. While results of this systematic review vary,
      they indicate a significant association between vitamin D status and AD and PD.

PMID- 29649129
TI  - Adsorption Removal of Multiple Dyes Using Biogenic Selenium Nanoparticles from an
      Escherichia coli Strain Overexpressed Selenite Reductase CsrF.
AB  - Selenite reductase CsrF overexpressed Escherichia coli was used as a microbial
      factory to produce Se(0) nanoparticles (Bio-SeNPs). The Bio-SeNPs were
      characterized by transmission electronic microscopy, element mapping, scanning
      electron microscopy, energy-dispersive X-ray spectrographs, Zeta-potential,
      dynamic light scattering, Fourier transform infrared spectroscopy and X-ray
      photoelectron spectroscopy analyses. The results indicated that Bio-SeNPs are
      irregular spheres with diameters from 60 to105 nm and mainly consist of Se(0),
      proteins and lipids. Furthermore, it exhibited maximum adsorption capacity for
      anionic dye (congo red) at acidic pH and cationic dyes (safranine T and methylene
      blue) at alkaline pH. To gain more insight, adsorption kinetics, adsorption
      isotherms and adsorption thermodynamics studies were carried out. These results
      showed that the adsorption capacities of congo red, safranine T and methylene
      blue were 1577.7, 1911.0 and 1792.2 mg/g, respectively. These adsorption
      processes were spontaneous and primarily physical reactions. In addition, Bio
      SeNPs can be effectively reused by 200 mmol/L NaCl. To the best of our knowledge,
      this is the first report of adsorption removal dyes by Bio-SeNPs. The adsorption
      capacities of Bio-SeNPs for congo red, safranine T and methylene blue were 6.8%,
      25.2% and 49.0% higher than that for traditional bio-based materials,
      respectively.

PMID- 29649130
TI  - Separation, Identification, and Antidiabetic Activity of Catechin Isolated from
      Arbutus unedo L. Plant Roots.
AB  - Phytopharmaceuticals play an essential role in medicine, since the need to
      investigate highly effective and safe drugs for the treatment of diabetes
      mellitus disease remains a significant challenge for modern medicine. Arbutus
      unedo L. root has various therapeutic properties, and has been used widely in the
      traditional medicine as an antidiabetic agent. The current study aimed to isolate
      the pharmacologically active compound from A. unedo roots using accelerated
      solvent extraction technology, to determine its chemical structure using
      different instrumental analytical methods, and also to evaluate the alpha
      glucosidase inhibitory activity. The roots of A. unedo were exhaustively
      extracted by high-pressure static extraction using the Zippertex(r) technology
      (Dionex-ASE, Paris, France), and the extract was mixed with XAD-16 resin to reach
      quantifiable amounts of active compounds which were identified by high-pressure
      liquid chromatography (HPLC), 1H NMR (300 MHz), and 13C NMR. The antidiabetic
      activity of the isolated compound was evaluated using the alpha-glucosidase
      inhibitory assay. The active compound was isolated, and its structure was
      identified as catechin using instrumental analysis.The results revealed that the
      isolated compound has potential alpha-glucosidase inhibitory activity with an
      IC50 value of 87.55 +/- 2.23 MUg/mL greater than acarbose. This was used as a
      positive control, which has an IC50 value of 199.53 +/- 1.12 MUg/mL. According to
      the results achieved, the roots of A. unedo were considered the best source of
      catechin and the Zippertex(r) technology method of extraction is the best method
      for isolation of this therapeutic active compound. In addition, the alpha
      glucosidase inhibitory activity results confirmed the traditional use of A. unedo
      roots as an antidiabetic agent. Future clinical trials and investigations of
      antidiabetic and other pharmacological effects such as anticancer are required.

PMID- 29649131
TI  - Identifying Patients with Atrioventricular Septal Defect in Down Syndrome
      Populations by Using Self-Normalizing Neural Networks and Feature Selection.
AB  - Atrioventricular septal defect (AVSD) is a clinically significant subtype of
      congenital heart disease (CHD) that severely influences the health of babies
      during birth and is associated with Down syndrome (DS). Thus, exploring the
      differences in functional genes in DS samples with and without AVSD is a critical
      way to investigate the complex association between AVSD and DS. In this study, we
      present a computational method to distinguish DS patients with AVSD from those
      without AVSD using the newly proposed self-normalizing neural network (SNN).
      First, each patient was encoded by using the copy number of probes on chromosome
      21. The encoded features were ranked by the reliable Monte Carlo feature
      selection (MCFS) method to obtain a ranked feature list. Based on this feature
      list, we used a two-stage incremental feature selection to construct two series
      of feature subsets and applied SNNs to build classifiers to identify optimal
      features. Results show that 2737 optimal features were obtained, and the
      corresponding optimal SNN classifier constructed on optimal features yielded a
      Matthew's correlation coefficient (MCC) value of 0.748. For comparison, random
      forest was also used to build classifiers and uncover optimal features. This
      method received an optimal MCC value of 0.582 when top 132 features were
      utilized. Finally, we analyzed some key features derived from the optimal
      features in SNNs found in literature support to further reveal their essential
      roles.

PMID- 29649132
TI  - Effect of Climate and Land Use on the Spatio-Temporal Variability of Tick-Borne
      Bacteria in Europe.
AB  - The incidence of tick-borne diseases caused by Borrelia burgdorferi sensu lato,
      Anaplasma phagocytophilum and Rickettsia spp. has been rising in Europe in recent
      decades. Early pre-assessment of acarological hazard still represents a complex
      challenge. The aim of this study was to model Ixodes ricinus questing nymph
      density and its infection rate with B. burgdorferi s.l., A. phagocytophilum and
      Rickettsia spp. in five European countries (Italy, Germany, Czech Republic,
      Slovakia, Hungary) in various land cover types differing in use and
      anthropisation (agricultural, urban and natural) with climatic and environmental
      factors (Normalized Difference Vegetation Index (NDVI), Normalized Difference
      Water Index (NDWI), Land Surface Temperature (LST) and precipitation). We show
      that the relative abundance of questing nymphs was significantly associated with
      climatic conditions, such as higher values of NDVI recorded in the sampling
      period, while no differences were observed among land use categories. However,
      the density of infected nymphs (DIN) also depended on the pathogen considered and
      land use. These results contribute to a better understanding of the variation in
      acarological hazard for Ixodes ricinus transmitted pathogens in Central Europe
      and provide the basis for more focused ecological studies aimed at assessing the
      effect of land use in different sites on tick-host pathogens interaction.

PMID- 29649134
TI  - "Gnothi Seauton": Leveraging the Host Response to Improve Influenza Virus Vaccine
      Efficacy.
AB  - Vaccination against the seasonal influenza virus is the best way to prevent
      infection. Nevertheless, vaccine efficacy remains far from optimal especially in
      high-risk populations such as the elderly. Recent technological advancements have
      facilitated rapid and precise identification of the B and T cell epitopes that
      are targets for protective responses. While these discoveries have undoubtedly
      brought the field closer to "universal" influenza virus vaccines, choosing the
      correct antigen is only one piece of the equation. Achieving efficacy and
      durability requires a detailed understanding of the diverse host factors and
      pathways that are required for attaining optimal responses. Sequencing
      technologies, systems biology, and immunological studies have recently advanced
      our understanding of the diverse aspects of the host response required for
      vaccine efficacy. In this paper, we review the critical role of the host response
      in determining efficacious responses and discuss the gaps in knowledge that will
      need to be addressed if the field is to be successful in developing new and more
      effective influenza virus vaccines.

PMID- 29649133
TI  - Current Approaches Including Novel Nano/Microtechniques to Reduce Silicone
      Implant-Induced Contracture with Adverse Immune Responses.
AB  - Capsular contracture, which is the pathologic development of fibrous capsules
      around implants, is a major complication of reconstructive and aesthetic breast
      surgeries. Capsular contracture can cause implant failure with breast hardening,
      deformity, and severe pain. The exact mechanisms underlying this complication
      remain unclear. In addition, anaplastic large cell lymphoma is now widely
      recognized as a very rare disease associated with breast implants. Foreign body
      reactions are an inevitable common denominator of capsular contracture. A number
      of studies have focused on the associated immune responses and their regulation.
      The present article provides an overview of the currently available techniques,
      including novel nano/microtechniques, to reduce silicone implant-induced
      contracture and associated foreign body responses.

PMID- 29649135
TI  - Development and Validation of a Microtiter Plate-Based Assay for Determination of
      Bacteriophage Host Range and Virulence.
AB  - Bacteriophages, which are the natural predators of bacteria, have re-emerged as
      an attractive alternative to combat antibiotic resistant bacteria. Phages are
      highly specific at the species and strain level and measurement of the phage host
      range plays an important role in utilizing the phage as antimicrobials. The most
      common method for phage host range determination has been to spot phage lysates
      on soft agar overlays and observe plaque formation. In this study, a liquid
      culture-based assay was developed in a 96-well microtiter plate format to measure
      the phage host range and virulence for a collection of 15 Salmonella phages
      against a panel of 20 Salmonella strains representing 11 serovars. This method
      was compared to a traditional spot method. The majority of the host range results
      from two methods were in agreement including in cases where a bacterial strain
      was insensitive to the phage. Each method produced a false-negative result in
      19/300 (6%) of the measured phage-host combinations when compared to the other
      method. The spot method tended to indicate greater phage sensitivity than the
      microtiter assay even though direct comparisons of the response magnitude between
      the two methods is difficult since they operate on different mechanisms. The
      microtiter plate assay was able to provide data on both the phage host range and
      virulence in greater resolution in a high-throughput format.

PMID- 29649136
TI  - Perineuronal Nets in Spinal Motoneurones: Chondroitin Sulphate Proteoglycan
      around Alpha Motoneurones.
AB  - Perineuronal nets (PNNs) are extracellular matrix structures surrounding neuronal
      sub-populations throughout the central nervous system, regulating plasticity.
      Enzymatically removing PNNs successfully enhances plasticity and thus functional
      recovery, particularly in spinal cord injury models. While PNNs within various
      brain regions are well studied, much of the composition and associated
      populations in the spinal cord is yet unknown. We aim to investigate the
      populations of PNN neurones involved in this functional motor recovery.
      Immunohistochemistry for choline acetyltransferase (labelling motoneurones), PNNs
      using Wisteria floribunda agglutinin (WFA) and chondroitin sulphate proteoglycans
      (CSPGs), including aggrecan, was performed to characterise the molecular
      heterogeneity of PNNs in rat spinal motoneurones (Mns). CSPG-positive PNNs
      surrounded ~70-80% of Mns. Using WFA, only ~60% of the CSPG-positive PNNs co
      localised with WFA in the spinal Mns, while ~15-30% of Mns showed CSPG-positive
      but WFA-negative PNNs. Selective labelling revealed that aggrecan encircled ~90%
      of alpha Mns. The results indicate that (1) aggrecan labels spinal PNNs better
      than WFA, and (2) there are differences in PNN composition and their associated
      neuronal populations between the spinal cord and cortex. Insights into the role
      of PNNs and their molecular heterogeneity in the spinal motor pools could aid in
      designing targeted strategies to enhance functional recovery post-injury.

PMID- 29649137
TI  - A Phenotype Classification of Internet Use Disorder in a Large-Scale High-School
      Study.
AB  - Internet Use Disorder (IUD) affects numerous adolescents worldwide, and
      (Internet) Gaming Disorder, a specific subtype of IUD, has recently been included
      in DSM-5 and ICD-11. Epidemiological studies have identified prevalence rates up
      to 5.7% among adolescents in Germany. However, little is known about the risk
      development during adolescence and its association to education. The aim of this
      study was to: (a) identify a clinically relevant latent profile in a large-scale
      high-school sample; (b) estimate prevalence rates of IUD for distinct age groups
      and (c) investigate associations to gender and education. N = 5387 adolescents
      out of 41 schools in Germany aged 11-21 were assessed using the Compulsive
      Internet Use Scale (CIUS). Latent profile analyses showed five profile groups
      with differences in CIUS response pattern, age and school type. IUD was found in
      6.1% and high-risk Internet use in 13.9% of the total sample. Two peaks were
      found in prevalence rates indicating the highest risk of IUD in age groups 15-16
      and 19-21. Prevalence did not differ significantly between boys and girls. High
      level education schools showed the lowest (4.9%) and vocational secondary schools
      the highest prevalence rate (7.8%). The differences between school types could
      not be explained by academic level.

PMID- 29649138
TI  - Response of Myeloid Leukemia Cells to Luteolin is Modulated by Differentially
      Expressed Pituitary Tumor-Transforming Gene 1 (PTTG1) Oncoprotein.
AB  - Luteolin, a flavonoid nutraceutical abundant in vegetables and fruits, exhibits a
      wide range of bioactive properties, including antioxidant, anti-inflammatory and
      anti-cancer activities. Pituitary tumor-transforming gene 1 (PTTG1), an
      oncoprotein that regulates cell proliferation, is highly expressed in several
      types of cancer cells including leukemia. In this study, we aim to investigate
      the anti-cancer effects of luteolin on cells with differential PTTG1 expression
      and their underlying mechanisms in human myeloid leukemia cells. Methyl thiazolyl
      tetrazolium (MTT) assay data showed that luteolin (25-100 MUM) significantly
      reduced cell viability in THP-1, HL-60 and K562 cells but did not affect normal
      peripheral blood mononuclear cells (PBMCs). Flow cytometric analysis and Western
      blot data demonstrated that luteolin induced a stronger apoptosis on
      undifferentiated myeloid leukemia cells with higher PTTG1 protein levels than on
      12-myristate 13-acetate (PMA)- or all-trans-retinoic acid (ATRA)-differentiated
      cells with lower PTTG1 expression. Furthermore, PTTG1 knockdown by shRNA in
      leukemia cells suppressed cell proliferation, arrested cell-cycle progression and
      impaired the effectiveness of luteolin on cell-cycle regulation. Moreover, PTTG1
      knockdown cells with luteolin exposure presented a reduction of the apoptotic
      proteins and maintained higher levels of the anti-apoptotic proteins such as Mcl
      1, Bcl-2 and p21, which exhibited greater resistance to apoptosis. Finally,
      microarray analysis showed that 20 genes associated with cell proliferation, such
      as CXCL10, VEGFA, TNF, TP63 and FGFR1, were dramatically down-regulated in PTTG1
      knockdown cells. Our current findings clearly demonstrate that luteolin-triggered
      leukemic cell apoptosis is modulated by the differential expression of the PTTG1.
      PTTG1 oncoprotein overexpression may modulate cell proliferation-related
      regulators and enhance the response of myeloid leukemia cells to luteolin.
      Luteolin is beneficial for the treatment of cancer cells with highly expressed
      PTTG1 oncoprotein.

PMID- 29649139
TI  - Assessing Photosensitizer Targeting Using Meso-Tetra(Carboxyphenyl) Porphyrin.
AB  - Mesotetra(4-carboxyphenyl)porphyrin (mTCPP) is a commercially available small
      molecule fluorophore and photosensitizer with four free carboxylic acid groups.
      mTCPP can readily be conjugated with amines for facile attachment of functional
      groups. In this work, we synthesized and assessed tetravalent, lysine-conjugated
      mTCPP, for its potential applications in targeted imaging and photodynamic
      therapy. Fmoc-protected d-lysine or l-lysine was conjugated to mTCPP via amide
      coupling with the epsilon amine group of lysine, followed by Fmoc deprotection.
      The resulting compounds did not dissolve well in aqueous solvent, but could be
      solubilized with the assistance of surfactants, including cholic acid. The l
      amino acid transporter (LAT1) can uptake diverse neutral l-amino acids. In vitro
      studies with U87 cells revealed a non-specific uptake of the hydrophobic Fmoc
      protected lysine-conjugated mTCPP precursors, but not d- or l-lysine mTCPP.
      Likewise, only the Fmoc-protected compounds induced substantial phototoxicty in
      cells following incubation and irradiation with blue light. These experimental
      results do not provide evidence to suggest that lysine-mTCPP is able to
      specifically target cancer cells. However, they do highlight mTCPP as a
      convenient and accessible framework for assessing molecular targeting of
      photosensitizers.

PMID- 29649140
TI  - Wound Stress, an Unheeded Factor for Echinacoside Accumulation in Cistanche
      deserticola Y. C. Ma.
AB  - Cistanche deserticola Y. C. Ma, a precious parasitic medicinal herb distributed
      in desert areas in the Northwest of China, also known as "desert ginseng", has
      been used in China for thousands of years for its nourishing effects. The
      phenylethanoid glycosides (PeGs) have been proven as the main effective compounds
      due to their neuroprotective effects and were used for quality control. In this
      study, echinacoside content, a representative PeG, total phenolic content, DPPH
      scavenging activity, and PAL activity were determined in different tissues of C.
      deserticola. Our results showed that most indices had a similar pattern of scale
      > cambium ring > pith and bottom part > middle part > upper part. Besides,
      stereomicroscopic observation showed that the scale surface was densely covered
      with physical wounds formed during vertical and broadwise growth in sand. Thus,
      wound area was quantified and a linear regression analysis was conducted between
      wound area and PAL activity, total phenolics, and echinacoside content. Our
      results suggested that physical wounding caused by sand might play an important
      role in echinacoside biosynthesis which has never been noticed in C. deserticola
      development. Furthermore, the coexistence of the highest PAL activity and highest
      echinacoside accumulation in scale tissue might indicate that the biosynthetic
      site of echinacoside in C. deseticola Y. C. Ma is mainly in the scale tissue.

PMID- 29649141
TI  - Anticancer Activity of Anthopleura anjunae Oligopeptides in Prostate Cancer DU
      145 Cells.
AB  - Anthopleura anjunae anti-tumor peptide (AAP-H) is a pentapeptide from the sea
      anemone Anthopleura anjunae with an amino acid sequence of Tyr-Val-Pro-Gly-Pro
      that is obtained by alkaline protease enzymatic hydrolysis extraction. In this
      study, we investigated the inhibitory effects of AAP-H on prostate cancer DU-145
      cell proliferation using a methylthiazolyldiphenyl-tetrazolium bromide assay.
      Cell morphology was analyzed by hematoxylin-eosin staining, acridine
      orange/ethidium bromide fluorescence staining, Hoechst 33258 fluorescence
      staining, and scanning electron microscopy. The mitochondrial membrane potential
      was determined by flow cytometry following JC-1 staining. The cell apoptosis rate
      was measured by Annexin V-fluorescein isothiocyanate and propidium iodide
      staining followed by flow cytometric analysis, and the expression of apoptosis
      associated proteins was assayed by Western blotting. The results demonstrated
      that AAP-H induced significant reductions in the number of viable cells and
      increased cell death in both a dose-dependent and time-dependent manner, with an
      IC50 of approximately 9.605 mM, 7.910 mM, and 2.298 mM at 24 h, 48 h, and 72 h,
      respectively. The morphologic characteristics of apoptotic cells were observed
      after treatment with AAP-H. The mitochondrial membrane potential was markedly
      decreased, and apoptosis increased after AAP-H treatment. Pro-apoptotic proteins,
      such as Bax, cytochrome-C, caspase-3, and caspase-9 were increased, but Bcl-2 was
      decreased. These findings suggest that AAP-H has moderate inhibitory effects on
      prostate cancer DU-145 cells, and the mechanism might involve the mitochondria
      mediated apoptotic pathway. Therefore, AAP-H is a candidate anti-prostate cancer
      drug or health-care food.

PMID- 29649142
TI  - Occurrence and Risk Assessment of PAHs in Surface Sediments from Western Arctic
      and Subarctic Oceans.
AB  - In the fourth Chinese National Arctic Research Expedition (from July to
      September, 2010), 14 surface sediment samples were collected from the Bering Sea,
      Chukchi Sea, and Canadian Basin to examine the spatial distributions, potential
      sources, as well as ecological and health risk assessment of polycyclic aromatic
      hydrocarbons (PAHs). The ?PAH (refers to the sum of 16 priority PAHs)
      concentration range from 27.66 ng/g to 167.48 ng/g (dry weight, d.w.).
      Additionally, the concentrations of ?PAH were highest in the margin edges of the
      Canadian Basin, which may originate from coal combustion with an accumulation of
      Canadian point sources and river runoff due to the surface ocean currents. The
      lowest levels occurred in the northern of Canadian Basin, and the levels of ?PAH
      in the Chukchi Sea were slightly higher than those in the Being Sea. Three isomer
      ratios of PAHs (Phenanthrene/Anthracene, BaA/(BaA+Chy), and LMW/HMW) were used to
      investigate the potential sources of PAHs, which showed the main source of
      combustion combined with weaker petroleum contribution. Compared with four
      sediment quality guidelines, the concentrations of PAH are much lower, indicating
      a low potential ecological risk. All TEQPAH also showed a low risk to human
      health. Our study revealed the important role of the ocean current on the
      redistribution of PAHs in the Arctic.

PMID- 29649143
TI  - Epigenetic and Transcriptional Modifications in Repetitive Elements in Petrol
      Station Workers Exposed to Benzene and MTBE.
AB  - Benzene, a known human carcinogen, and methyl tert-butyl ether (MTBE), not
      classifiable as to its carcinogenicity, are fuel-related pollutants. This study
      investigated the effect of these chemicals on epigenetic and transcriptional
      alterations in DNA repetitive elements. In 89 petrol station workers and 90 non
      occupationally exposed subjects the transcriptional activity of retrotransposons
      (LINE-1, Alu), the methylation on repeated-element DNA, and of H3K9 histone, were
      investigated in peripheral blood lymphocytes. Median work shift exposure to
      benzene and MTBE was 59 and 408 ug/m3 in petrol station workers, and 4 and 3.5
      ug/m3, in controls. Urinary benzene (BEN-U), S-phenylmercapturic acid, and MTBE
      were significantly higher in workers than in controls, while trans,trans-muconic
      acid (tt-MA) was comparable between the two groups. Increased BEN-U was
      associated with increased Alu-Y and Alu-J expression; moreover, increased tt-MA
      was associated with increased Alu-Y and Alu-J and LINE-1 (L1)-5'UTR expression.
      Among repetitive element methylation, only L1-Pa5 was hypomethylated in petrol
      station workers compared to controls. While L1-Ta and Alu-YD6 methylation was not
      associated with benzene exposure, a negative association with urinary MTBE was
      observed. The methylation status of histone H3K9 was not associated with either
      benzene or MTBE exposure. Overall, these findings only partially support previous
      observations linking benzene exposure with global DNA hypomethylation.

PMID- 29649146
TI  - Pure FPGA Implementation of an HOG Based Real-Time Pedestrian Detection System.
AB  - In this study, we propose a real-time pedestrian detection system using a FPGA
      with a digital image sensor. Comparing with some prior works, the proposed
      implementation realizes both the histogram of oriented gradients (HOG) and the
      trained support vector machine (SVM) classification on a FPGA. Moreover, the
      implementation does not use any external memory or processors to assist the
      implementation. Although the implementation implements both the HOG algorithm and
      the SVM classification in hardware without using any external memory modules and
      processors, the proposed implementation's resource utilization of the FPGA is
      lower than most of the prior art. The main reasons resulting in the lower
      resource usage are: (1) simplification in the Getting Bin sub-module; (2)
      distributed writing and two shift registers in the Cell Histogram Generation sub
      module; (3) reuse of each sum of the cell histogram in the Block Histogram
      Normalization sub-module; and (4) regarding a window of the SVM classification as
      105 blocks of the SVM classification. Moreover, compared to Dalal and Triggs's
      pure software HOG implementation, the proposed implementation's average detection
      rate is just about 4.05% less, but can achieve a much higher frame rate.

PMID- 29649145
TI  - Combined Effect of Anticancer Agents and Cytochrome C Decorated Hybrid
      Nanoparticles for Liver Cancer Therapy.
AB  - Hepatocellular carcinoma is an aggressive form of liver cancer that displays
      minimal symptoms until its late stages. Unfortunately, patient prognosis still
      remains poor with only 10% of patients surviving more than five years after
      diagnosis. Current chemotherapies alone are not offering efficient treatment,
      hence alternative therapeutic approaches are urgently required. In this work, we
      highlight the potential of combination of treatment of hepatocellular carcinoma
      with existing chemotherapies in combination with pro-apoptotic factor cytochrome
      C. In order to allow cytochrome C to cross the cellular membrane and become
      internalized, it has been immobilised onto the surface of hybrid iron oxide-gold
      nanoparticles. This novel approach has been tested in vitro on HepG2, Huh-7D and
      SK-hep-1 cell lines in order to elucidate potential as a possible alternative
      therapy with greater efficacy. The data from our studies show consistently that
      combining treatment of clinically used anticancer agents (doxorubicin,
      paclitaxel, oxaliplatin, vinblastine and vincristine) significantly increases the
      levels of apoptosis within the cell lines, which leads to cellular death. Hence,
      this combined approach may hold promise for future treatment regimes.

PMID- 29649144
TI  - A Novel G-Protein-Coupled Receptors Gene from Upland Cotton Enhances Salt Stress
      Tolerance in Transgenic Arabidopsis.
AB  - Plants have developed a number of survival strategies which are significant for
      enhancing their adaptation to various biotic and abiotic stress factors. At the
      transcriptome level, G-protein-coupled receptors (GPCRs) are of great
      significance, enabling the plants to detect a wide range of endogenous and
      exogenous signals which are employed by the plants in regulating various
      responses in development and adaptation. In this research work, we carried out
      genome-wide analysis of target of Myb1 (TOM1), a member of the GPCR gene family.
      The functional role of TOM1 in salt stress tolerance was studied using a
      transgenic Arabidopsis plants over-expressing the gene. By the use of the
      functional domain PF06454, we obtained 16 TOM genes members in Gossypium
      hirsutum, 9 in Gossypium arboreum, and 11 in Gossypium raimondii. The genes had
      varying physiochemical properties, and it is significant to note that all the
      grand average of hydropathy (GRAVY) values were less than one, indicating that
      all are hydrophobic in nature. In all the genes analysed here, both the exonic
      and intronic regions were found. The expression level of Gh_A07G0747 (GhTOM) was
      significantly high in the transgenic lines as compared to the wild type; a
      similar trend in expression was observed in all the salt-related genes tested in
      this study. The study in epidermal cells confirmed the localization of the
      protein coded by the gene TOM1 in the plasma membrane. Analysis of anti-oxidant
      enzymes showed higher concentrations of antioxidants in transgenic lines and
      relatively lower levels of oxidant substances such as H2O2. The low
      malondialdehyde (MDA) level in transgenic lines indicated that the transgenic
      lines had relatively low level of oxidative damage compared to the wild types.
      The results obtained indicate that Gh_A07G0747 (GhTOM) can be a putative target
      gene for enhancing salt stress tolerance in plants and could be exploited in the
      future for the development of salt stress-tolerant cotton cultivars.

PMID- 29649147
TI  - A Convex Constraint Variational Method for Restoring Blurred Images in the
      Presence of Alpha-Stable Noises.
AB  - Blurred image restoration poses a great challenge under the non-Gaussian noise
      environments in various communication systems. In order to restore images from
      blur and alpha-stable noise while also preserving their edges, this paper
      proposes a variational method to restore the blurred images with alpha-stable
      noises based on the property of the meridian distribution and the total variation
      (TV). Since the variational model is non-convex, it cannot guarantee a global
      optimal solution. To overcome this drawback, we also incorporate an additional
      penalty term into the deblurring and denoising model and propose a strictly
      convex variational method. Due to the convexity of our model, the primal-dual
      algorithm is adopted to solve this convex variational problem. Our simulation
      results validate the proposed method.

PMID- 29649148
TI  - Discrimination of Temperature and Strain in Brillouin Optical Time Domain
      Analysis Using a Multicore Optical Fiber.
AB  - Brillouin optical time domain analysis is the sensing of temperature and strain
      changes along an optical fiber by measuring the frequency shift changes of
      Brillouin backscattering. Because frequency shift changes are a linear
      combination of temperature and strain changes, their discrimination is a
      challenge. Here, a multicore optical fiber that has two cores is fabricated. The
      differences between the cores' temperature and strain coefficients are such that
      temperature (strain) changes can be discriminated with error amplification
      factors of 4.57  degrees C/MHz (69.11 MU epsilon /MHz), which is 2.63 (3.67)
      times lower than previously demonstrated. As proof of principle, using the
      multicore optical fiber and a commercial Brillouin optical time domain analyzer,
      the temperature (strain) changes of a thermally expanding metal cylinder are
      discriminated with an error of 0.24% (3.7%).

PMID- 29649149
TI  - Vehicular Visible Light Networks for Urban Mobile Crowd Sensing.
AB  - Crowd sensing is a powerful tool to map and predict interests and events. In the
      future, it could be boosted by an increasing number of connected vehicles sharing
      information and intentions. This will be made available by on board wireless
      connected devices able to continuously communicate with other vehicles and with
      the environment. Among the enabling technologies, visible light communication
      (VLC) represents a low cost solution in the short term. In spite of the fact that
      vehicular communications cannot rely on the sole VLC due to the limitation
      provided by the light which allows communications in visibility only, VLC can
      however be considered to complement other wireless communication technologies
      which could be overloaded in dense scenarios. In this paper we evaluate the
      performance of VLC connected vehicles when urban crowd sensing is addressed and
      we compare the performance of sole vehicular visible light networks with that of
      VLC as a complementary technology of IEEE 802.11p. Results, obtained through a
      realistic simulation tool taking into account both the roadmap constraints and
      the technologies protocols, help to understand when VLC provides the major
      improvement in terms of delivered data varying the number and position of RSUs
      and the FOV of the receiver.

PMID- 29649150
TI  - Self-Alignment MEMS IMU Method Based on the Rotation Modulation Technique on a
      Swing Base.
AB  - The micro-electro-mechanical-system (MEMS) inertial measurement unit (IMU) has
      been widely used in the field of inertial navigation due to its small size, low
      cost, and light weight, but aligning MEMS IMUs remains a challenge for
      researchers. MEMS IMUs have been conventionally aligned on a static base,
      requiring other sensors, such as magnetometers or satellites, to provide
      auxiliary information, which limits its application range to some extent.
      Therefore, improving the alignment accuracy of MEMS IMU as much as possible under
      swing conditions is of considerable value. This paper proposes an alignment
      method based on the rotation modulation technique (RMT), which is completely self
      aligned, unlike the existing alignment techniques. The effect of the inertial
      sensor errors is mitigated by rotating the IMU. Then, inertial frame-based
      alignment using the rotation modulation technique (RMT-IFBA) achieved coarse
      alignment on the swing base. The strong tracking filter (STF) further improved
      the alignment accuracy. The performance of the proposed method was validated with
      a physical experiment, and the results of the alignment showed that the standard
      deviations of pitch, roll, and heading angle were 0.0140  degrees  , 0.0097 
      degrees  , and 0.91  degrees  , respectively, which verified the practicality and
      efficacy of the proposed method for the self-alignment of the MEMS IMU on a swing
      base.

PMID- 29649152
TI  - Study on Interference Suppression Algorithms for Electronic Noses: A Review.
AB  - Electronic noses (e-nose) are composed of an appropriate pattern recognition
      system and a gas sensor array with a certain degree of specificity and broad
      spectrum characteristics. The gas sensors have their own shortcomings of being
      highly sensitive to interferences which has an impact on the detection of target
      gases. When there are interferences, the performance of the e-nose will
      deteriorate. Therefore, it is urgent to study interference suppression techniques
      for e-noses. This paper summarizes the sources of interferences and reviews the
      advances made in recent years in interference suppression for e-noses. According
      to the factors which cause interference, interferences can be classified into two
      types: interference caused by changes of operating conditions and interference
      caused by hardware failures. The existing suppression methods were summarized and
      analyzed from these two aspects. Since the interferences of e-noses are uncertain
      and unstable, it can be found that some nonlinear methods have good effects for
      interference suppression, such as methods based on transfer learning, adaptive
      methods, etc.

PMID- 29649151
TI  - DNA Methylation and Histone Modification in Hypertension.
AB  - Systemic hypertension, which eventually results in heart failure, renal failure
      or stroke, is a common chronic human disorder that particularly affects elders.
      Although many signaling pathways involved in the development of hypertension have
      been reported over the past decades, which has led to the implementation of a
      wide variety of anti-hypertensive therapies, one half of all hypertensive
      patients still do not have their blood pressure controlled. The frontier in
      understanding the molecular mechanisms underlying hypertension has now advanced
      to the level of epigenomics. Particularly, increasing evidence is emerging that
      DNA methylation and histone modifications play an important role in gene
      regulation and are involved in alteration of the phenotype and function of
      vascular cells in response to environmental stresses. This review seeks to
      highlight the recent advances in our knowledge of the epigenetic regulations and
      mechanisms of hypertension, focusing on the role of DNA methylation and histone
      modification in the vascular wall. A better understanding of the epigenomic
      regulation in the hypertensive vessel may lead to the identification of novel
      target molecules that, in turn, may lead to novel drug discoveries for the
      treatment of hypertension.

PMID- 29649153
TI  - Health Impacts of Ambient Air Pollution in Finland.
AB  - Air pollution has been estimated to be one of the leading environmental health
      risks in Finland. National health impact estimates existing to date have focused
      on particles (PM) and ozone (O3). In this work, we quantify the impacts of
      particles, ozone, and nitrogen dioxide (NO2) in 2015, and analyze the related
      uncertainties. The exposures were estimated with a high spatial resolution
      chemical transport model, and adjusted to observed concentrations. We calculated
      the health impacts according to Word Health Organization (WHO) working group
      recommendations. According to our results, ambient air pollution caused a burden
      of 34,800 disability-adjusted life years (DALY). Fine particles were the main
      contributor (74%) to the disease burden, which is in line with the earlier
      studies. The attributable burden was dominated by mortality (32,900 years of life
      lost (YLL); 95%). Impacts differed between population age groups. The burden was
      clearly higher in the adult population over 30 years (98%), due to the dominant
      role of mortality impacts. Uncertainties due to the concentration-response
      functions were larger than those related to exposures.

PMID- 29649154
TI  - Chemical and Nutritional Composition of Terminalia ferdinandiana (Kakadu Plum)
      Kernels: A Novel Nutrition Source.
AB  - Terminalia ferdinandiana (Kakadu plum) is a native Australian fruit. Industrial
      processing of T. ferdinandiana fruits into puree generates seeds as a by-product,
      which are generally discarded. The aim of our present study was to process the
      seed to separate the kernel and determine its nutritional composition. The
      proximate, mineral and fatty acid compositions were analysed in this study.
      Kernels are composed of 35% fat, while proteins account for 32% dry weight (DW).
      The energy content and fiber were 2065 KJ/100 g and 21.2% DW, respectively.
      Furthermore, the study showed that kernels were a very rich source of minerals
      and trace elements, such as potassium (6693 mg/kg), calcium (5385 mg/kg), iron
      (61 mg/kg) and zinc (60 mg/kg) DW, and had low levels of heavy metals. The fatty
      acid composition of the kernels consisted of omega-6 fatty acid, linoleic acid
      (50.2%), monounsaturated oleic acid (29.3%) and two saturated fatty acids namely
      palmitic acid (12.0%) and stearic acid (7.2%). The results indicate that T.
      ferdinandiana kernels have the potential to be utilized as a novel protein source
      for dietary purposes and non-conventional supply of linoleic, palmitic and oleic
      acids.

PMID- 29649155
TI  - Efficient Active Oxygen Free Radical Generated in Tumor Cell by Loading
      (HCONH2).H2O2 Delivery Nanosystem with Soft-X-ray Radiotherapy.
AB  - Tumor hypoxia is known to result in radiotherapy resistance and traditional
      radiotherapy using super-hard X-ray irradiation can cause considerable damage to
      normal tissue. Therefore, formamide peroxide (FPO) with high reactive oxygen
      content was employed to enhance the oxygen concentration in tumor cells and
      increase the radio-sensitivity of low-energy soft-X-ray. To improve stability of
      FPO, FPO is encapsulated into polyacrylic acid (PAA)-coated hollow mesoporous
      silica nanoparticles (FPO@HMSNs-PAA). On account of the pH-responsiveness of PAA,
      FPO@HMSNs-PAA will release more FPO in simulated acidic tumor microenvironment
      (pH 6.50) and subcellular endosomes (pH 5.0) than in simulated normal tissue
      media (pH 7.40). When exposed to soft-X-ray irradiation, the released FPO
      decomposes into oxygen and the generated oxygen further formed many reactive
      oxygen species (ROS), leading to significant tumor cell death. The ROS-mediated
      cytotoxicity of FPO@HMSNs-PAA was confirmed by ROS-induced green fluorescence in
      tumor cells. The presented FPO delivery system with soft-X-ray irradiation paves
      a way for developing the next opportunities of radiotherapy toward efficient
      tumor prognosis.

PMID- 29649156
TI  - Using Landscape Analysis to Test Hypotheses about Drivers of Tick Abundance and
      Infection Prevalence with Borrelia burgdorferi.
AB  - Patterns of vector-borne disease risk are changing globally in space and time and
      elevated disease risk of vector-borne infection can be driven by anthropogenic
      modification of the environment. Incidence of Lyme disease, caused by the
      bacterium Borrelia burgdorferi sensu stricto, has risen in a number of locations
      in North America and this increase may be driven by spatially or numerically
      expanding populations of the primary tick vector, Ixodes scapularis. We used a
      model selection approach to identify habitat fragmentation and land-use/land
      cover variables to test the hypothesis that the amount and configuration of
      forest cover at spatial scales relevant to deer, the primary hosts of adult
      ticks, would be the predominant determinants of tick abundance. We expected that
      land cover heterogeneity and amount of forest edge, a habitat thought to
      facilitate deer foraging and survival, would be the strongest driver of tick
      density and that larger spatial scales (5-10 km) would be more important than
      smaller scales (1 km). We generated metrics of deciduous and mixed forest
      fragmentation using Fragstats 4.4 implemented in ArcMap 10.3 and found, after
      adjusting for multicollinearity, that total forest edge within a 5 km buffer had
      a significant negative effect on tick density and that the proportion of forested
      land cover within a 10 km buffer was positively associated with density of I.
      scapularis nymphs. None of the 1 km fragmentation metrics were found to
      significantly improve the fit of the model. Elevation, previously associated with
      increased density of I. scapularis nymphs in Virginia, while significantly
      predictive in univariate analysis, was not an important driver of nymph density
      relative to fragmentation metrics. Our results suggest that amount of forest
      cover (i.e., lack of fragmentation) is the most important driver of I. scapularis
      density in our study system.

PMID- 29649158
TI  - Dietary Intakes of Minerals, Essential and Toxic Trace Elements for Adults from
      Eragrostis tef L.: A Nutritional Assessment.
AB  - This study analysed the contents of thirty-six mineral and trace elements in teff
      (Eragrostis tef L.) grains. What is more, dietary intakes were calculated.
      Inductively coupled plasma mass spectrometry (ICP-MS) was used to assess mineral
      and trace element contents. Consequently, the appropriate Recommended Dietary
      Allowance (RDA) or adequate intake (AI), and provisional tolerable weekly intake
      (PTWI) or provisional tolerable monthly intake (PTMI) values for adults were
      determined according to the Food and Agriculture Organization/World Health
      Organization (FAO/WHO) and Institute of Medicine (IOM) regulations. Teff is a
      significant contributor to RDAs and AIs for females in the following order: Mn >
      Cu > Zn >= Mg > Fe >= P and Ca. For males, teff contributes in the order, Mn > Cu
      > Fe > Zn >= P >= Mg > and Ca. The concentration of arsenic (65.9 ug/kg) in brown
      teff originating in Bolivia exceeded the average acceptable value set by Reg. No.
      1881 of 6-50 ug/kg in cereals consumed in the EU. The PTWIs or PTMIs for Al, Cd,
      Sn and Hg were all under 7%, which is below the limits of toxic element intake
      related to the body weight of 65 kg for adult females and 80 kg for males, set by
      the FAO/WHO. Teff grains can be recommended as a valuable and safe source of
      minerals and trace elements.

PMID- 29649157
TI  - Triclosan Lacks Anti-Estrogenic Effects in Zebrafish Cells but Modulates Estrogen
      Response in Zebrafish Embryos.
AB  - Triclosan (TCS), an antimicrobial agent widely found in the aquatic environment,
      is suspected to act as an endocrine disrupting compound, however mechanistic
      information is lacking in regards to aquatic species. This study assessed the
      ability of TCS to interfere with estrogen receptor (ER) transcriptional activity,
      in zebrafish-specific in vitro and in vivo reporter gene assays. We report that
      TCS exhibits a lack of either agonistic or antagonistic effects on a panel of ER
      expressing zebrafish (ZELH-zfERalpha and -zfERbeta) and human (MELN) cell lines.
      At the organism level, TCS at concentrations of up to 0.3 uM had no effect on ER
      regulated brain aromatase gene expression in transgenic cyp19a1b-GFP zebrafish
      embryos. At a concentration of 1 uM, TCS interfered with the E2 response in an
      ambivalent manner by potentializing a low E2 response (0.625 nM), but decreasing
      a high E2 response (10 nM). Altogether, our study suggests that while modulation
      of ER-regulated genes by TCS may occur in zebrafish, it does so irrespective of a
      direct binding and activation of zfERs.

PMID- 29649159
TI  - Astaxanthin Restrains Nitrative-Oxidative Peroxidation in Mitochondrial-Mimetic
      Liposomes: A Pre-Apoptosis Model.
AB  - Astaxanthin (ASTA) is a ketocarotenoid found in many marine organisms and that
      affords many benefits to human health. ASTA is particularly effective against
      radical-mediated lipid peroxidation, and recent findings hypothesize a
      "mitochondrial-targeted" action of ASTA in cells. Therefore, we examined the
      protective effects of ASTA against lipid peroxidation in zwitterionic
      phosphatidylcholine liposomes (PCLs) and anionic phosphatidylcholine:
      phosphatidylglycerol liposomes (PCPGLs), at different pHs (6.2 to 8.0), which
      were challenged by oxidizing/nitrating conditions that mimic the regular and
      preapoptotic redox environment of active mitochondria. Pre-apoptotic conditions
      were created by oxidized/nitr(osyl)ated cytochrome c and resulted in the highest
      levels of lipoperoxidation in both PCL and PCPGLs (pH 7.4). ASTA was less
      protective at acidic conditions, especially in anionic PCPGLs. Our data
      demonstrated the ability of ASTA to hamper oxidative and nitrative events that
      lead to cytochrome c-peroxidase apoptosis and lipid peroxidation, although its
      efficiency changes with pH and lipid composition of membranes.

PMID- 29649160
TI  - Eye on the Ball: Table Tennis as a Pro-Health Form of Leisure-Time Physical
      Activity.
AB  - Background: The article is devoted to an analysis of leisure-time (amateur) table
      tennis in Poland, its practitioners and the regularities of their activity.
      Methods: The study examined 12,406 persons in 4689 households (representative for
      the population). We used binary logistic regression and descriptive statistics in
      order to identify the patterns and determinants of table-tennis practice in
      Poland. Results: Table tennis is practised by 2.8% of population, and by 6.6% of
      physically active Poles. Among adults it is predominantly an occasional
      recreational game, not performed as a sport per se. Among children, it is often
      the part of physical education (PE) classes. Statistically significant predictors
      of contact with table tennis are: gender, age, income, place of residence,
      children in the household and being a student. Conclusions: Due to the undeniable
      benefits of table tennis (health, pleasure, personal and social development), the
      sport is recommended for use as a tool in increasing the (overall low) physical
      activity of Poles. Its popularization requires promotion in the media (as a
      health-oriented activity) and using various channels, including public places,
      the workplace (as part of corporate social responsibility) and physical education
      classes at school.

PMID- 29649161
TI  - Domain-Specific Adult Sedentary Behaviour Questionnaire (ASBQ) and the GPAQ
      Single-Item Question: A Reliability and Validity Study in an Asian Population.
AB  - This study examined the validity and reliability of a domain-specific Adult
      Sedentary Behaviour Questionnaire (ASBQ) and the Global Physical Activity
      Questionnaire (GPAQ) single-item sitting question using self- and interviewer
      administered modes of administration against the triaxial ActiGraph wGT3X-BT
      accelerometer. The ASBQ and the GPAQ were administered twice, seven days apart.
      Participants were asked to put on the waist-worn accelerometer for seven days.
      Convergent validity was assessed using Spearman's rho, mean absolute error (MAE),
      and Bland-Altman analysis (n = 78). Reliability was assessed using the Spearman's
      rho and intraclass correlation coefficient (ICC) (n = 84). Participants were
      adults aged 20-65 years and identifying as Chinese, Malay, or Indian. Only the
      self-administered GPAQ was significantly correlated with accelerometry-based
      measures (rho: 0.46), but not the interviewer-administered version (rho: 0.12).
      MAE for GPAQ was 207.5-218.3 min/day in relation to the accelerometer and for
      ASBQ was 154.7-174.6 min/day. Bland-Altman plots demonstrated large limits of
      agreement between questionnaire and accelerometry-based measures. While the self
      administered GPAQ demonstrated a moderate correlation with accelerometry, the
      mean bias and the limits of agreement were large. The GPAQ (rho: 0.68-0.79; ICC:
      0.68-0.78) and the ASBQ (rho: 0.53-0.64; ICC: 0.66-0.74) showed moderate-to-good
      reliability for total sedentary time using either self- or interviewer
      administration. Future research should incorporate accelerometers to generate
      useful sedentary behaviour measures.

PMID- 29649163
TI  - Physio-Microstructural Properties of Aerated Cement Slurry for Lightweight
      Structures.
AB  - Cementitious composites, including ferrocement and continuous fiber reinforced
      cement, are increasingly considered for building construction and repair. One
      alternative in processing of these composites is to infiltrate the reinforcement
      (continuous fibers or chicken mesh) with a flowable cementitious slurry. The
      relatively high density of cementitious binders, when compared with polymeric
      binders, are a setback in efforts to introduce cementitious composites as lower
      cost, fire-resistant, and durable alternatives to polymer composites. Aeration of
      the slurry is an effective means of reducing the density of cementitious
      composites. This approach, however, compromises the mechanical properties of
      cementitious binders. An experimental program was undertaken in order to assess
      the potential for production of aerated slurry with a desired balance of density,
      mechanical performance, and barrier qualities. The potential for nondestructive
      monitoring of strength development in aerated cementitious slurry was also
      investigated. This research produced aerated slurries with densities as low as
      0.9 g/cm3 with viable mechanical and barrier qualities for production of
      composites. The microstructure of these composites was also investigated.

PMID- 29649162
TI  - Identification by Molecular Docking ofHomoisoflavones from Leopoldia comosa as
      Ligands of Estrogen Receptors.
AB  - The physiological responses to estrogen hormones are mediated within specific
      tissues by at least two distinct receptors, ER and ER. Several natural and
      synthetic molecules show activity by interacting with these proteins. In
      particular, a number of vegetal compounds known as phytoestrogens shows
      estrogenic or anti-estrogenic activity. The majority of these compounds belongs
      to the isoflavones family and the most representative one, genistein, shows anti
      proliferative effects on various hormone-sensitive cancer cells, including
      breast, ovarian and prostate cancer. In this work we describe the identification
      of structurally related homoisoflavones isolated from Leopoldia comosa (L.) Parl.
      (L. comosa), a perennial bulbous plant, potentially useful as hormonal
      substitutes or complements in cancer treatments. Two of these compounds have been
      selected as potential ligands of estrogen receptors (ERs) and the interaction
      with both isoforms of estrogen receptors have been investigated through molecular
      docking on their crystallographic structures. The results provide evidence of the
      binding of these compounds to the target receptors and their interactions with
      key residues of the active sites of the two proteins, and thus they could
      represent suitable leads for the development of novel tools for the dissection of
      ER signaling and the development of new pharmacological treatments in hormone
      sensitive cancers.

PMID- 29649164
TI  - The Impact of Abdominal Fat Levels on All-Cause Mortality Risk in Patients
      Undergoing Hemodialysis.
AB  - Although an increased body mass index is associated with lower mortality in
      patients undergoing hemodialysis (HD), known as the "obesity paradox," the
      relationship of abdominal fat levels with all-cause mortality has rarely been
      studied. We investigated the impact of computed-tomography-measured abdominal fat
      levels (visceral fat area (VFA) and subcutaneous fat area (SFA)) on all-cause
      mortality in this population. A total of 201 patients undergoing HD were enrolled
      and cross-classified by VFA and SFA levels according to each cutoff point, VFA of
      78.7 cm2 and SFA of 93.2 cm2, based on the receiver operator characteristic (ROC)
      curve as following; group 1 (G1): lower VFA and lower SFA, G2: higher VFA and
      lower SFA, G3: lower VFA and higher SFA, G4: higher VFA and higher SFA. During a
      median follow-up of 4.3 years, 67 patients died. Kaplan-Meier analysis revealed
      10-year survival rates of 29.0%, 50.0%, 62.6%, and 72.4% in G1, G2, G3, and G4 (p
      < 0.0001), respectively. The adjusted hazard ratio was 0.30 (95% confidence
      interval [CI] 0.05-1.09, p = 0.070) for G2 vs. G1, 0.37 (95% CI 0.18-0.76, p =
      0.0065) for G3 vs. G1, and 0.21 (95% CI 0.07-0.62, p = 0.0035) for G4 vs. G1,
      respectively. In conclusion, combined SFA and VFA levels were negatively
      associated with risks for all-cause mortality in patients undergoing HD. These
      results are a manifestation of the "obesity paradox."

PMID- 29649165
TI  - Use of a Survey to Assess the Environmental Exposure and Family Perception to
      Lead in Children (<6 Years) in Four Valley Cities, Northwestern China.
AB  - With the growth of industry, the extensive use of lead, and urban expansion in
      Northwestern Valley Cities (NVC) China, there is probable reason for presuming an
      increasing risk of lead exposure. However, little is known about the lead
      exposure of children less than 6 years old in NVC. As a first investigation, this
      study uses a survey to systematically determine the influences of various risk
      factors within the family environment, parents' background, children's behavior,
      mother's behavior during pregnancy, and parental perception about children's
      blood lead (CBL). A total of 596 families were recruited from the general
      population in Urumqi, Lanzhou, Xining and Yan'an. Parents, and their children (<6
      years old), were asked about the environment and behaviors which could possibly
      relate with lead exposure. The results indicated that in the typical NVC of
      China, children's environment and behavior, parents' education level, and
      mother's pregnancy behavior, were associated with potential CBL. It was noted
      that not all parents in NVC China recognized the importance of children's lead
      exposure. Therefore, children's health care and medical screening campaigns need
      to be designed to improve family's fundamental knowledge of lead hazards,
      associated health effects, and prevention in the NVC of China.

PMID- 29649166
TI  - Tumor-Associated Macrophages and Mast Cells Positive to Tryptase Are Correlated
      with Angiogenesis in Surgically-Treated Gastric Cancer Patients.
AB  - Mast cells and macrophages can play a role in tumor angiogenesis by stimulating
      microvascular density (MVD). The density of mast cells positive to tryptase
      (MCDPT), tumor-associated macrophages (TAMs), and MVD were evaluated in a series
      of 86 gastric cancer (GC) tissue samples from patients who had undergone
      potential curative surgery. MCDPT, TAMs, and MVD were assessed in tumor tissue
      (TT) and in adjacent normal tissue (ANT) by immunohistochemistry and image
      analysis. Each of the above parameters was correlated with the others and, in
      particular for TT, with important clinico-pathological features. In TT, a
      significant correlation between MCDPT, TAMs, and MVD was found by Pearson t-test
      analysis (p ranged from 0.01 to 0.02). No correlation to the clinico-pathological
      features was found. A significant difference in terms of mean MCDPT, TAMs, and
      MVD between TT and ANT was found (p ranged from 0.001 to 0.002). Obtained data
      suggest MCDPT, TAMs, and MVD increased from ANT to TT. Interestingly, MCDPT and
      TAMs are linked in the tumor microenvironment and they play a role in GC
      angiogenesis in a synergistic manner. The assessment of the combination of MCDPT
      and TAMs could represent a surrogate marker of angiogenesis and could be
      evaluated as a target of novel anti-angiogenic therapies in GC patients.

PMID- 29649167
TI  - Assessment of Indoor Air Quality Problems in Office-Like Environments: Role of
      Occupational Health Services.
AB  - There is an increasing concern about indoor air quality (IAQ) and its impact on
      health, comfort, and work-performance in office-like environments and their
      workers, which account for most of the labor force. The Scientific Committee on
      Indoor Air Quality and Health of the ICOH (Int. Comm. Occup. Health) has
      discussed the assessment and management of IAQ problems and proposed a stepwise
      approach to be conducted by a multidisciplinary team. It is recommended to
      integrate the building assessment, inspection by walk-through of the office
      workplace, questionnaire survey, and environmental measurements, in that order.
      The survey should cover perceived IAQ, symptoms, and psychosocial working
      aspects. The outcome can be used for mapping the IAQ and to prioritize the order
      in which problems should be dealt with. Individual health surveillance in
      relation to IAQ is proposed only when periodical health surveillance is already
      performed for other risks (e.g., video display units) or when specific clinical
      examination of workers is required due to the occurrence of diseases that may be
      linked to IAQ (e.g., Legionnaire's disease), recurrent inflammation, infections
      of eyes, respiratory airway effects, and sensorial disturbances. Environmental
      and personal risk factors should also be compiled and assessed. Workplace health
      promotion should include programs for smoking cessation and stress and IAQ
      management.

PMID- 29649169
TI  - Development and Characterization of Novel Genic-SSR Markers in Apple-Juniper Rust
      Pathogen Gymnosporangium yamadae (Pucciniales: Pucciniaceae) Using Next
      Generation Sequencing.
AB  - The Apple-Juniper rust, Gymnosporangium yamadae, is an economically important
      pathogen of apples and junipers in Asia. The absence of markers has hampered the
      study of the genetic diversity of this widespread pathogen. In our study, we
      developed twenty-two novel microsatellite markers for G. yamadae from randomly
      sequenced regions of the transcriptome, using next-generation sequencing methods.
      These polymorphic markers were also tested on 96 G. yamadae individuals from two
      geographical populations. The allele numbers ranged from 2 to 9 with an average
      value of 6 per locus. The polymorphism information content (PIC) values ranged
      from 0.099 to 0.782 with an average value of 0.48. Furthermore, the observed (HO)
      and expected (HE) heterozygosity ranged from 0.000 to 0.683 and 0.04 to 0.820,
      respectively. These novel developed microsatellites provide abundant molecular
      markers for investigating the genetic structure and genetic diversity of G.
      yamadae, which will help us to better understand disease epidemics and the origin
      and migration routes of the Apple-Juniper rust pathogen. Further studies will
      also be completed to dissect how human activities influence the formation of
      current population structures. Furthermore, these SSR (simple sequence repeat)
      markers can also be used as tools to identify virulence by mapping the whole
      genomes of different virulent populations. These markers will, thus, assist the
      development of effective risk-assessment models and management systems for the
      Apple-Juniper rust pathogen.

PMID- 29649168
TI  - Structure-Function Relationship of Transporters in the Glutamate-Glutamine Cycle
      of the Central Nervous System.
AB  - Many kinds of transporters contribute to glutamatergic excitatory synaptic
      transmission. Glutamate is loaded into synaptic vesicles by vesicular glutamate
      transporters to be released from presynaptic terminals. After synaptic vesicle
      release, glutamate is taken up by neurons or astrocytes to terminate the signal
      and to prepare for the next signal. Glutamate transporters on the plasma membrane
      are responsible for transporting glutamate from extracellular fluid to cytoplasm.
      Glutamate taken up by astrocyte is converted to glutamine by glutamine synthetase
      and transported back to neurons through glutamine transporters on the plasma
      membranes of the astrocytes and then on neurons. Glutamine is converted back to
      glutamate by glutaminase in the neuronal cytoplasm and then loaded into synaptic
      vesicles again. Here, the structures of glutamate transporters and glutamine
      transporters, their conformational changes, and how they use electrochemical
      gradients of various ions for substrate transport are summarized. Pharmacological
      regulations of these transporters are also discussed.

PMID- 29649171
TI  - In Situ 3D Monitoring of Geometric Signatures in the Powder-Bed-Fusion Additive
      Manufacturing Process via Vision Sensing Methods.
AB  - Lack of monitoring of the in situ process signatures is one of the challenges
      that has been restricting the improvement of Powder-Bed-Fusion Additive
      Manufacturing (PBF AM). Among various process signatures.

PMID- 29649170
TI  - UFLC-Q-TOF-MS/MS-Based Screening and Identification of Flavonoids and Derived
      Metabolites in Human Urine after Oral Administration of Exocarpium Citri Grandis
      Extract.
AB  - Exocarpium Citri grandis (ECG) is an important Traditional Chinese Medicine (TCM)
      for the treatment of cough and phlegm, and the flavonoids contained were
      considered the main effective components. To date, the systematic chemical
      profiling of these flavonoids and derived in vivo metabolites in human have not
      been well investigated. ECG was extracted using boiling water and then provided
      to volunteers for oral administration. Following the ingestion, urine samples
      were collected from volunteers over 48 h. The extract and urine samples were
      analyzed using ultra-fast liquid chromatography/quadrupole-time-of-flight tandem
      mass spectrometry (UFLC-Q-TOF-MS/MS) system to screen and identify flavonoids and
      derived in vivo metabolites. A total of 18 flavonoids were identified in the ECG
      extract, and 20 metabolites, mainly glucuronide and sulfate conjugates, were
      screened in urine samples collected post consumption. The overall excretion of
      naringenin metabolites corresponded to 5.45% of intake and occurred mainly within
      4-12 h after the ingestion. Meanwhile, another 29 phenolic catabolites were
      detected in urine. Obtained data revealed that flavonoids were abundant in the
      ECG extract, and these components underwent extensive phase II metabolism in
      humans. These results provided valuable information for further study of the
      pharmacology and mechanism of action of ECG.

PMID- 29649172
TI  - Hadoop Oriented Smart Cities Architecture.
AB  - A smart city implies a consistent use of technology for the benefit of the
      community. As the city develops over time, components and subsystems such as
      smart grids, smart water management, smart traffic and transportation systems,
      smart waste management systems, smart security systems, or e-governance are
      added. These components ingest and generate a multitude of structured, semi
      structured or unstructured data that may be processed using a variety of
      algorithms in batches, micro batches or in real-time. The ICT architecture must
      be able to handle the increased storage and processing needs. When vertical
      scaling is no longer a viable solution, Hadoop can offer efficient linear
      horizontal scaling, solving storage, processing, and data analyses problems in
      many ways. This enables architects and developers to choose a stack according to
      their needs and skill-levels. In this paper, we propose a Hadoop-based
      architectural stack that can provide the ICT backbone for efficiently managing a
      smart city. On the one hand, Hadoop, together with Spark and the plethora of
      NoSQL databases and accompanying Apache projects, is a mature ecosystem. This is
      one of the reasons why it is an attractive option for a Smart City architecture.
      On the other hand, it is also very dynamic; things can change very quickly, and
      many new frameworks, products and options continue to emerge as others decline.
      To construct an optimized, modern architecture, we discuss and compare various
      products and engines based on a process that takes into consideration how the
      products perform and scale, as well as the reusability of the code, innovations,
      features, and support and interest in online communities.

PMID- 29649173
TI  - A Three-Dimensional Target Depth-Resolution Method with a Single-Vector Sensor.
AB  - This paper mainly studies and verifies the target number category-resolution
      method in multi-target cases and the target depth-resolution method of aerial
      targets. Firstly, target depth resolution is performed by using the sign
      distribution of the reactive component of the vertical complex acoustic
      intensity; the target category and the number resolution in multi-target cases is
      realized with a combination of the bearing-time recording information; and the
      corresponding simulation verification is carried out. The algorithm proposed in
      this paper can distinguish between the single-target multi-line spectrum case and
      the multi-target multi-line spectrum case. This paper presents an improved
      azimuth-estimation method for multi-target cases, which makes the estimation
      results more accurate. Using the Monte Carlo simulation, the feasibility of the
      proposed target number and category-resolution algorithm in multi-target cases is
      verified. In addition, by studying the field characteristics of the aerial and
      surface targets, the simulation results verify that there is only amplitude
      difference between the aerial target field and the surface target field under the
      same environmental parameters, and an aerial target can be treated as a special
      case of a surface target; the aerial target category resolution can then be
      realized based on the sign distribution of the reactive component of the vertical
      acoustic intensity so as to realize three-dimensional target depth resolution. By
      processing data from a sea experiment, the feasibility of the proposed aerial
      target three-dimensional depth-resolution algorithm is verified.

PMID- 29649174
TI  - Crowdsourcing-Assisted Radio Environment Database for V2V Communication.
AB  - In order to realize reliable Vehicle-to-Vehicle (V2V) communication systems for
      autonomous driving, the recognition of radio propagation becomes an important
      technology. However, in the current wireless distributed network systems, it is
      difficult to accurately estimate the radio propagation characteristics because of
      the locality of the radio propagation caused by surrounding buildings and
      geographical features. In this paper, we propose a measurement-based radio
      environment database for improving the accuracy of the radio environment
      estimation in the V2V communication systems. The database first gathers
      measurement datasets of the received signal strength indicator (RSSI) related to
      the transmission/reception locations from V2V systems. By using the datasets, the
      average received power maps linked with transmitter and receiver locations are
      generated. We have performed measurement campaigns of V2V communications in the
      real environment to observe RSSI for the database construction. Our results show
      that the proposed method has higher accuracy of the radio propagation estimation
      than the conventional path loss model-based estimation.

PMID- 29649175
TI  - A Multi-Technology Communication Platform for Urban Mobile Sensing.
AB  - A common concern in smart cities is the focus on sensing procedures to provide
      city-wide information to city managers and citizens. To meet the growing demands
      of smart cities, the network must provide the ability to handle a large number of
      mobile sensors/devices, with high heterogeneity and unpredictable mobility, by
      collecting and delivering the sensed information for future treatment. This work
      proposes a multi-wireless technology communication platform for opportunistic
      data gathering and data exchange with respect to smart cities. Through the
      implementation of a proprietary long-range (LoRa) network and an urban sensor
      network, our platform addresses the heterogeneity of Internet of Things (IoT)
      devices while conferring communications in an opportunistic manner, increasing
      the interoperability of our platform. It implements and evaluates a medium access
      communication (MAC) protocol for LoRa networks with multiple gateways. It also
      implements mobile Opportunistic VEhicular (mOVE), a delay-tolerant network (DTN)
      based architecture to address the mobility dimension. The platform provides
      vehicle-to-everything (V2X) communication with support for highly reliable and
      actionable information flows. Moreover, taking into account the high mobility
      pattern that a smart city scenario presents, we propose and evaluate two
      forwarding strategies for the opportunistic sensor network.

PMID- 29649176
TI  - Improving Efficiency of Passive RFID Tag Anti-Collision Protocol Using Dynamic
      Frame Adjustment and Optimal Splitting.
AB  - Radio frequency identification is a wireless communication technology, which
      enables data gathering and identifies recognition from any tagged object. The
      number of collisions produced during wireless communication would lead to a
      variety of problems including unwanted number of iterations and reader-induced
      idle slots, computational complexity in terms of estimation as well as
      recognition of the number of tags. In this work, dynamic frame adjustment and
      optimal splitting are employed together in the proposed algorithm. In the dynamic
      frame adjustment method, the length of frames is based on the quantity of tags to
      yield optimal efficiency. The optimal splitting method is conceived with smaller
      duration of idle slots using an optimal value for splitting level M o p t , where
      (M > 2), to vary slot sizes to get the minimal identification time for the idle
      slots. The application of the proposed algorithm offers the advantages of not
      going for the cumbersome estimation of the quantity of tags incurred and the size
      (number) of tags has no effect on its performance efficiency. Our experiment
      results show that using the proposed algorithm, the efficiency curve remains
      constant as the number of tags varies from 50 to 450, resulting in an overall
      theoretical gain in the efficiency of 0.032 compared to system efficiency of
      0.441 and thus outperforming both dynamic binary tree slotted ALOHA (DBTSA) and
      binary splitting protocols.

PMID- 29649177
TI  - Practical 3-D Beam Pattern Based Channel Modeling for Multi-Polarized Massive
      MIMO Systems.
AB  - In this paper, a practical non-stationary three-dimensional (3-D) channel models
      for massive multiple-input multiple-output (MIMO) systems, considering beam
      patterns for different antenna elements, is proposed. The beam patterns using
      dipole antenna elements with different phase excitation toward the different
      direction of travels (DoTs) contributes various correlation weights for rays
      related towards/from the cluster, thus providing different elevation angle of
      arrivals (EAoAs) and elevation angle of departures (EAoDs) for each antenna
      element. These include the movements of the user that makes our channel to be a
      non-stationary model of clusters at the receiver (RX) on both the time and array
      axes. In addition, their impacts on 3-D massive MIMO channels are investigated
      via statistical properties including received spatial correlation. Additionally,
      the impact of elevation/azimuth angles of arrival on received spatial correlation
      is discussed. Furthermore, experimental validation of the proposed 3-D channel
      models on azimuth and elevation angles of the polarized antenna are specifically
      evaluated and compared through simulations. The proposed 3-D generic models are
      verified using relevant measurement data.

PMID- 29649178
TI  - Synthesis and Application of the Transition Metal Complexes of alpha-Pyridinyl
      Alcohols, alpha-Bipyridinyl Alcohols, alpha,alpha'-Pyridinyl Diols and
      alpha,alpha'-Bipyridinyl Diols in Homogeneous Catalysis.
AB  - The paper presents a comprehensive survey on the synthetic procedures of
      transition metal complexes of alpha-pyridinyl alcoholato, alpha-bipyridinyl
      alcoholato, alpha,alpha'-pyridinyl dialcoholato and alpha,alpha'-bipyridinyl
      dialcoholato ligands and their coordination chemistry. Greater emphasis is,
      however, given to the catalytic activity of the complexes in homogeneous and
      asymmetric chemical reactions. The multidentate character of the pyridinyl
      alcohols and/or bipyridinyl diols is of great importance in the complexation with
      a large number and type of transition metals. The transition metal complexes of
      pyridinyl alcoholato or bipyridinyl dialcoholato ligands in most cases, and a few
      pyridinyl alcohols alone, were used as catalysts in homogeneous and chemical
      asymmetric reactions. In most of the homogeneously catalysed enantioselective
      chemical reactions, limited numbers and types of pyridinyl alcohols and or
      bipyridinyl diols were used in the preparation of chiral catalysts that led to a
      few investigations on the catalytic importance of the pyridinyl alcohols.

PMID- 29649179
TI  - Nanocoatings for Chronic Wound Repair-Modulation of Microbial Colonization and
      Biofilm Formation.
AB  - Wound healing involves a complex interaction between immunity and other natural
      host processes, and to succeed it requires a well-defined cascade of events.
      Chronic wound infections can be mono- or polymicrobial but their major
      characteristic is their ability to develop a biofilm. A biofilm reduces the
      effectiveness of treatment and increases resistance. A biofilm is an ecosystem on
      its own, enabling the bacteria and the host to establish different social
      interactions, such as competition or cooperation. With an increasing incidence of
      chronic wounds and, implicitly, of chronic biofilm infections, there is a need
      for alternative therapeutic agents. Nanotechnology shows promising openings,
      either by the intrinsic antimicrobial properties of nanoparticles or their
      function as drug carriers. Nanoparticles and nanostructured coatings can be
      active at low concentrations toward a large variety of infectious agents; thus,
      they are unlikely to elicit emergence of resistance. Nanoparticles might
      contribute to the modulation of microbial colonization and biofilm formation in
      wounds. This comprehensive review comprises the pathogenesis of chronic wounds,
      the role of chronic wound colonization and infection in the healing process, the
      conventional and alternative topical therapeutic approaches designed to combat
      infection and stimulate healing, as well as revolutionizing therapies such as
      nanotechnology-based wound healing approaches.

PMID- 29649181
TI  - Minor Neurological Dysfunctions (MNDs) in Autistic Children without Intellectual
      Disability.
AB  - BACKGROUND: Children with autism spectrum disorder (ASD) require neurological
      evaluation to detect sensory-motor impairment. This will improve understanding of
      brain function in children with ASD, in terms of minor neurological dysfunctions
      (MNDs). METHODS: We compared 32 ASD children without intellectual disability (IQ
      >= 70) with 32 healthy controls. A standardized and age-specific neurological
      examination according to Touwen was used to detect the presence of MNDs.
      Particular attention was paid to severity and type of MNDs. RESULTS: Children
      with ASD had significantly higher rates of MNDs compared to controls (96.9%
      versus 15.6%): 81.3% had simple MNDs (p < 0.0001) and 15.6% had complex MNDs (p =
      0.053). The prevalence of MNDs in the ASD group was significantly higher (p <
      0.0001) than controls. With respect to specific types of MNDs, children with ASD
      showed a wide range of fine manipulative disability, sensory deficits and
      choreiform dyskinesia. We also found an excess of associated movements and
      anomalies in coordination and balance. CONCLUSIONS: Results replicate previous
      findings which found delays in sensory-motor behavior in ASD pointing towards a
      role for prenatal, natal and neonatal risk factors in the neurodevelopmental
      theory of autism.

PMID- 29649180
TI  - Establishing a Split Luciferase Assay for Proteinkinase G (PKG) Interaction
      Studies.
AB  - Nitric oxide (NO/cyclic guanosine monophosphate (cGMP)-regulated cellular
      mechanisms are involved in a variety of (patho-) physiological processes. One of
      the main effector molecules in this system, proteinkinase G (PKG), serves as a
      molecular switch by phosphorylating different target proteins and thereby turning
      them on or off. To date, only a few interaction partners of PKG have been
      described although the identification of protein-protein interactions (PPI) is
      indispensable for the understanding of cellular processes and diseases.
      Conventionally used methods to detect PPIs exhibit several disadvantages, e.g.,
      co-immunoprecipitations, which depend on suitable high-affinity antibodies.
      Therefore, we established a cell-based protein-fragment complementation assay
      (PCA) for the identification of PKG target proteins. Here, a reporter protein
      (click beetle luciferase) is split into two fragments and fused to two different
      possible interaction partners. If interaction occurs, the reporter protein is
      functionally complemented and the catalyzed reaction can then be quantitatively
      measured. By using this technique, we confirmed the regulator of G-Protein
      signaling 2 (RGS2) as an interaction partner of PKGIalpha (a PKG-isoform)
      following stimulation with 8-Br-cGMP and 8-pCPT-cGMP. Hence, our results support
      the conclusion that the established approach could serve as a novel tool for the
      rapid, easy and cost-efficient detection of novel PKG target proteins.

PMID- 29649183
TI  - Transcriptome and Metabolome Analyses Reveal That Nitrate Strongly Promotes
      Nitrogen and Carbon Metabolism in Soybean Roots, but Tends to Repress It in
      Nodules.
AB  - Leguminous plants form root nodules with rhizobia that fix atmospheric dinitrogen
      (N2) for the nitrogen (N) nutrient. Combined nitrogen sources, particular
      nitrate, severely repress nodule growth and nitrogen fixation activity in
      soybeans (Glycine max [L.] Merr.). A microarray-based transcriptome analysis and
      the metabolome analysis were carried out for the roots and nodules of
      hydroponically grown soybean plants treated with 5 mM of nitrate for 24 h and
      compared with control without nitrate. Gene expression ratios of nitrate vs. the
      control were highly enhanced for those probesets related to nitrate transport and
      assimilation and carbon metabolism in the roots, but much less so in the nodules,
      except for the nitrate transport and asparagine synthetase. From the metabolome
      analysis, the concentration ratios of metabolites for the nitrate treatment vs.
      the control indicated that most of the amino acids, phosphorous-compounds and
      organic acids in roots were increased about twofold in the roots, whereas in the
      nodules most of the concentrations of the amino acids, P-compounds and organic
      acids were decreased while asparagine increased exceptionally. These results may
      support the hypothesis that nitrate primarily promotes nitrogen and carbon
      metabolism in the roots, but mainly represses this metabolism in the nodules.

PMID- 29649182
TI  - Applications of Microalgal Biotechnology for Disease Control in Aquaculture.
AB  - Aquaculture industries, and in particular the farming of fish and crustaceans,
      are major contributors to the economy of many countries and an increasingly
      important component in global food supply. However, the severe impact of aquatic
      microbial diseases on production performance remains a challenge to these
      industries. This article considers the potential applications of microalgal
      technology in the control of such diseases. At the simplest level, microalgae
      offer health-promoting benefits as a nutritional supplement in feed meal because
      of their digestibility and high content of proteins, lipids and essential
      nutrients. Furthermore, some microalgal species possess natural anti-microbial
      compounds or contain biomolecules that can serve as immunostimulants. In
      addition, emerging genetic engineering technologies in microalgae offer the
      possibility of producing 'functional feed additives' in which novel and specific
      bioactives, such as fish growth hormones, anti-bacterials, subunit vaccines, and
      virus-targeted interfering RNAs, are components of the algal supplement. The
      evaluation of such technologies for farm applications is an important step in the
      future development of sustainable aquaculture.

PMID- 29649185
TI  - Erratum: Vol. 66, No. 29.

PMID- 29649184
TI  - Immunopathological Characterization of Muscle Biopsy Samples from Immune-Mediated
      Necrotizing Myopathy Patients.
AB  - BACKGROUND Immune-mediated necrotizing myopathy (IMNM) is a relatively new
      proposed category of idiopathic inflammatory myopathies (IIMs), characterized by
      the presence of abundant necrotic muscle fibers, myophagocytosis, and sparse
      inflammatory infiltrates. The aim of our study was to analyze the
      immunopathological characteristics of IMNM by detecting biopsy samples from a
      cohort of patients, and to delineate the pathways involved in the pathogenesis.
      MATERIAL AND METHODS A retrospective evaluation of muscle biopsy samples,
      clinical and laboratory data, and immunohistochemical analysis of macrophages MHC
      I and MAC, was performed for all patients diagnosed as having IMNM but without a
      prior exposure to statins. RESULTS Immunohistochemical analysis revealed the
      presence of CD68+ macrophages mainly in the necrotic muscle fibers and the
      endomysial connective tissue. MHC-I and MAC positively stained not only the
      necrotic fibers or vessels but also the non-necrotic ones. CONCLUSIONS Our data
      describe general immunological features in IMNM patients, which may be helpful in
      serving as biomarkers, aid in diagnostic decisions, and provide clues into the
      underlying mechanisms involved in this disease.

PMID- 29649186
TI  - Current Marijuana Use by Industry and Occupation - Colorado, 2014-2015.
AB  - The effects of marijuana use on workplace safety are of concern for public health
      and workplace safety professionals. Twenty-nine states and the District of
      Columbia have enacted laws legalizing marijuana at the state level for
      recreational and/or medical purposes. Employers and safety professionals in
      states where marijuana use is legal have expressed concerns about potential
      increases in occupational injuries, such as on-the-job motor vehicle crashes,
      related to employee impairment. Data published in 2017 by the Colorado Department
      of Public Health and Environment (CDPHE) showed that more than one in eight adult
      state residents aged >=18 years currently used marijuana in 2014 (13.6%) and 2015
      (13.4%) (1). To examine current marijuana use by working adults and the
      industries and occupations in which they are employed, CDPHE analyzed data from
      the state's Behavioral Risk Factor Surveillance System (BRFSS) regarding current
      marijuana use (at least 1 day during the preceding 30 days) among 10,169 persons
      who responded to the current marijuana use question. During 2014 and 2015, 14.6%
      of these 10,169 Colorado workers reported current marijuana use, with the highest
      reported prevalence among workers in the Accommodation and Food Services industry
      (30.1%) and Food Preparation and Serving (32.2%) occupations. Understanding the
      industries and occupations of adults with reported marijuana use can help direct
      and maximize impact of public health messaging and potential safety interventions
      for adults.

PMID- 29649188
TI  - QuickStats: Age-Adjusted Suicide Rates,*,? by Race/Ethnicity - National Vital
      Statistics System, United States, 2015-2016.

PMID- 29649187
TI  - Surveillance to Track Progress Toward Polio Eradication - Worldwide, 2016-2017.
AB  - Global efforts to eradicate polio began in 1988, and four of the six World Health
      Organization (WHO) regions currently have achieved poliofree certification.
      Within the remaining two regions with endemic poliomyelitis (African and Eastern
      Mediterranean), Afghanistan, Nigeria, and Pakistan have never interrupted
      transmission of wild poliovirus (WPV). The primary means of detecting poliovirus
      transmission is surveillance for acute flaccid paralysis (AFP) among children
      aged <15 years, combined with collection and testing of stool specimens for
      detection of WPV and vaccine-derived polioviruses (VDPVs)* in WHO-accredited
      laboratories within the Global Polio Laboratory Network (GPLN) (1,2). AFP
      surveillance is supplemented by environmental surveillance for polioviruses in
      sewage from selected locations. Genomic sequencing of isolated polioviruses
      enables the mapping of transmission by time and place, assessment of potential
      gaps in surveillance, and identification of the emergence of VDPVs (3). This
      report presents poliovirus surveillance data from 2016-2017, with particular
      focus on six countries in the Eastern Mediterranean Region (EMR) and 20 countries
      in the African Region (AFR) that reported WPV or circulating VDPVs (cVDPVs)
      during 2011-2017. Included in the 20 AFR countries are the three most affected by
      the 2014-2015 Ebola virus disease (Ebola) outbreak (Guinea, Liberia, and Sierra
      Leone), even though only one (Guinea) reported WPV or cVDPVs during the
      surveillance period. During 2017, a total of 14 (70%) of the 20 AFR countries and
      five (83%) of the six EMR countries met both surveillance quality indicators at
      the national level; however, provincial-level variation was seen. Surveillance
      strengthening activities are needed in specific countries of these regions to
      provide evidence supporting ultimate certification of the interruption of
      poliovirus circulation.

PMID- 29649189
TI  - Acute Metam Sodium Poisoning Caused by Occupational Exposure at a Flower Farm -
      Uganda, October 2016.
AB  - On October 25, 2016, media reports alerted the Uganda Ministry of Health to an
      outbreak of >80 cases of vomiting, syncope, and acute diarrhea among workers at a
      flower farm in central Uganda; 27 workers were hospitalized. On November 1, an
      investigation was undertaken by the Uganda Public Health Fellowship Program.* A
      case-control study found that working inside greenhouse 7, which had been
      fumigated with the organosulfur compound metam sodium the night of October 13,
      was strongly associated with illness. Employees who worked in this greenhouse
      during October 14-21 reported a strong "suffocating" smell in the greenhouse.
      Investigation revealed that, in violation of safety protocols, workers did not
      properly cover the soil after fumigation, allowing vapors to become trapped
      inside the greenhouse. The farm management, unaware of the lapse, failed to
      inform workers to avoid the vicinity of the fumigation. Respiratory protective
      measures were not routinely available for workers, which likely contributed to
      the severity and extent of the outbreak. Although metam sodium is generally
      considered to be of low risk when used according to manufacturer's instructions
      (1), occupational exposure in the absence of recommended safety measures can have
      serious health consequences. The investigation highlighted the importance of
      identifying potential occupational hazards to workers, as well as establishing
      safety protocols in occupational settings, training workers at risk, such as
      pesticide sprayers and flower pickers,? and ensuring enforcement of safety
      protocols. After this outbreak, the farm management reviewed, revised, and
      trained the workers on safety protocols to prevent future outbreaks.

PMID- 29649191
TI  - Marketing unhealthy commodities on social media.

PMID- 29649190
TI  - Updated CDC Recommendations for Using Artemether-Lumefantrine for the Treatment
      of Uncomplicated Malaria in Pregnant Women in the United States.
AB  - Malaria infection during pregnancy is associated with an increased risk for
      maternal and fetal complications. In the United States, treatment options for
      uncomplicated, chloroquine-resistant Plasmodium falciparum and P. vivax malaria
      in pregnant women are limited to mefloquine or quinine plus clindamycin (1).
      However, limited availability of quinine and increasing resistance to mefloquine
      restrict these options. Strong evidence now demonstrates that artemether
      lumefantrine (AL) (Coartem) is effective and safe in the treatment of malaria in
      pregnancy. The World Health Organization (WHO) has endorsed artemisinin-based
      combination therapies (ACTs), such as AL, for treatment of uncomplicated malaria
      during the second and third trimesters of pregnancy and is currently considering
      whether to add ACTs, including AL, as an option for malaria treatment during the
      first trimester (2,3). This policy note reviews the evidence and updates CDC
      recommendations to include AL as a treatment option for uncomplicated malaria
      during the second and third trimesters of pregnancy and during the first
      trimester of pregnancy when other treatment options are unavailable. These
      updated recommendations reflect current evidence and are consistent with WHO
      treatment guidelines.

PMID- 29649192
TI  - Tobacco targets-doomed to fail?

PMID- 29649193
TI  - Volume, nature and potential impact of advertisements on Facebook and YouTube by
      food brands popular in New Zealand.
AB  - AIM: To analyse extent, nature and potential impact of marketing by food and
      beverage brands popular in New Zealand on Facebook and YouTube. METHOD: Popular
      food and beverage brands in New Zealand were selected from Socialbakers. Posts on
      Facebook pages of 45 packaged food, beverage and fast food companies over two
      months and YouTube channels of 15 companies over two years were analysed for
      nutritional quality and use of activities, promotional strategies (eg, cartoons)
      and premium offers (eg, competitions). RESULTS: The 45 brands selected made 762
      Facebook posts during October-November 2016. About 28% of posts were videos and
      2/3 (63%) contained at least one occasional (ie, unhealthy) food. Promotional
      strategies were used in 41% of posts, with a famous sportsperson/team being the
      most frequently used. Premium offers were used in 34% of posts, with competitions
      being the most frequently used. It was estimated some posts could potentially
      reach 10% of New Zealand adolescents. The 15 food brands selected posted about
      300 videos on their YouTube channels during 2015-2016. About 84% of videos
      contained food marketing and 77% of products marketed were occasional.
      Promotional strategies and premium offers were used in 61% and 24% of videos
      respectively, and the most common marketing techniques were the same as on
      Facebook. CONCLUSION: Social media is an important medium for food marketers in
      New Zealand and promotional strategies and premium offers are frequently used.
      Methodology needs to be developed to monitor actual exposure to such
      advertisements.

PMID- 29649194
TI  - Regulatory chills: tobacco industry legal threats and the politics of tobacco
      standardised packaging in New Zealand.
AB  - AIMS: To describe the process of enacting tobacco standardised packaging (SP)
      amidst tobacco industry legal threats in New Zealand. METHODS: Relevant
      government and NGO documents, and media items were reviewed. Policymakers and
      health advocates in New Zealand were interviewed. The data were triangulated and
      thematically analysed. RESULTS: In 2011, the New Zealand Government announced the
      goal of becoming a smokefree country (reducing smoking prevalence to 5%) by the
      year 2025, and considered adopting SP. In April 2012, the Government announced it
      would introduce SP, but tobacco companies threatened the Government with
      litigation in international courts for violating investment and intellectual
      property rights. In response, the Government adopted a 'wait and see' approach,
      waiting until two legal challenges against Australia's SP law were resolved
      before it enacted its legislation in September 2016. Health advocates, limited
      due to funding constraints, attempted to alter the Government's approach to the
      legal threats without success. Interviews with policymakers and health advocates
      confirmed these threats helped produce a regulatory chill, delaying the
      policymaking process by three years. CONCLUSION: The New Zealand case illustrates
      how the threat of a potential international lawsuit can create a chilling effect
      by helping delay the implementation of public health policies.

PMID- 29649195
TI  - Pertussis vaccination uptake in pregnancy: lessons to be learned from an
      integrated healthcare approach.
AB  - AIM: To determine the proportion of pregnant women vaccinated with the pertussis
      booster in the third trimester of their pregnancy, and explore factors
      influencing coverage. METHODS: A clinical audit was undertaken at Rotorua
      hospital using electronic databases to determine pertussis immunisation among
      women who birthed from 25 March to 25 April, 2017 (n=111). Lead maternity carers
      (LMCs) were surveyed to assess knowledge of the vaccine and explore suggestions
      to increase vaccination coverage. RESULTS: Only 44% (n=49) of women were
      vaccinated in 2017. Women 25 years and under, and women from Rotorua were less
      likely to be vaccinated. A woman not being recalled to the GP for vaccination was
      the biggest reason for not being vaccinated (n=27). Every woman in Taupo/Turangi
      was recalled in pregnancy, leading to greater vaccine uptake compared to women in
      Rotorua. CONCLUSION: Overall, the proportion of pregnant women vaccinated for
      pertussis continue to be low with coverage being disproportionally lower for
      younger women. The integrated healthcare approach in Taupo/Turangi has resulted
      in improved vaccine uptake. Interventions that allow general practitioners, LMCs
      and primary health organisations to work together can improve vaccination rates
      of pregnant mothers in New Zealand.

PMID- 29649196
TI  - Diagnosis of abdominal tuberculosis in Christchurch New Zealand: a case series.
AB  - AIM: Abdominal tuberculosis presents with non-specific symptoms, including
      generalised abdominal pain. Prompt and accurate diagnosis is critical to
      improving outcomes and avoiding complications. We conducted a retrospective
      review of cases of abdominal tuberculosis presenting to Christchurch Hospital to
      explore the epidemiology, clinical features and diagnostic modalities used.
      METHOD: Cases were identified by searching for relevant ICD discharge codes from
      January 1996 to January 2016. Data on age, clinical presentation, investigations
      and microbiological results were obtained. RESULTS: There were 20 patients
      diagnosed with abdominal tuberculosis over the study period. The median age was
      34. Thirteen patients were male (65%), seven female (35%). The majority (11) were
      from Asia (predominantly India), five were African, and three were New Zealand
      Europeans. Abdominal pain was the most common presenting symptom (70%) followed
      by fevers (50%) and night sweats (50%). The C-reactive protein was elevated in 15
      patients (75%), anaemia was found in 11 (55%) and nine had abnormal liver
      function tests (45%). Abdominal ultrasound (US) and computed tomography (CT)
      showed generic inflammatory change in all patients in this series (100%).
      Laparoscopy was undertaken in 10 (50%) patients, all of which had positive
      laparoscopic biopsies. Ascitic fluid was obtained in nine, with stains for acid
      fast bacilli uniformly negative, however three (33%) had mycobacterial growth
      from culture. Six colonoscopies were performed: in three (50%) culture and/or
      histology was positive. Three lymph node biopsies and two formal laparotomies
      were the remaining diagnostic techniques employed with two biopsies and one
      laparotomy yielding positive results. Overall, of the 20 cases, 15 (75%) were
      able to be definitively confirmed, with the remaining five treated presumptively
      for probable abdominal tuberculosis. CONCLUSION: Abdominal tuberculosis is an
      uncommon presentation at our institution, with an average of one case each year.
      The typical patient was a young immigrant from Asia or Africa. Diagnostic
      laparoscopy was the most common and uniformly reliable means of obtaining a
      definitive diagnosis.

PMID- 29649197
TI  - Metronidazole stewardship initiative at Christchurch hospitals-achievable with
      immediate benefits.
AB  - AIMS: To evaluate an antimicrobial stewardship (AMS) initiative to change
      hospital prescribing practice for metronidazole. METHODS: In October 2015, the
      Canterbury District Health Board (CDHB) AMS committee changed advice for
      metronidazole to promote two times daily dosing for most indications,
      prioritisation of the oral route and avoidance of double anaerobic cover.
      Adoption of the initiative was facilitated via change in prescribing guidelines,
      education and ongoing pharmacy support. Usage and expenditure on metronidazole
      for adult inpatients were compared for the five years pre- and two years post
      change. Other district health boards (DHBs) were surveyed to determine their
      dosing recommendation for metronidazole IV. RESULTS: Mean annual metronidazole IV
      use, as defined daily doses per 1,000 occupied bed days, decreased by 43% post
      initiative. Use of non-IV (oral or rectal) formulations increased by 104%. Total
      savings associated with the initiative were approximately $33,400 in drug costs
      plus $78,200 per annum in IV giving sets and post-dose flushes. Twelve of 20
      (60%) DHBs (including CDHB) endorse twice daily IV dosing. CONCLUSIONS: In
      addition to financial savings, reduction in IV doses has potential benefits,
      including avoidance of IV catheter-associated complications such as bloodstream
      infections. Approaches to metronidazole dosing vary across DHBs and could benefit
      from national coordination.

PMID- 29649198
TI  - Poisoning due to tutin in honey-a report of an outbreak in New Zealand.
AB  - AIM: In autumn 2008, an outbreak of toxic honey poisoning was identified. The
      outbreak was not recognised initially until three cases from one family group
      presented to hospital, with a common factor of recent consumption of locally
      produced honey. The aim of this study was to investigate potential cases of this
      honey poisoning and determine which toxin was involved. METHOD: The incident was
      investigated retrospectively by Waikato District Health Board's Population Health
      unit and the New Zealand Food Safety Authority (NZFSA). Identified patients were
      followed up by questionnaire to gather case information. HortResearch (now Plant
      and Food Research) tested honey samples for toxins. RESULTS: The causative agent
      was identified as tutin, which comes from the New Zealand native plant tutu
      (Coriaria arborea) which has long been known as a potential source of
      contamination of honey produced in the warmer parts of New Zealand. Retrospective
      case investigation identified a total of 22 possible or probable cases, based on
      a clinical case definition. The spectrum of toxic effects reported were broadly
      similar to those previously described for tutin, derived either directly from the
      plant itself or indirectly from honey. There were 13 samples of honey, linked to
      symptomatic individuals, which were available for testing. Of these, 10 were
      positive for tutin and its hydroxy metabolite hyenanchin (hydroxytutin) and one
      was positive for hyenanchin alone. CONCLUSION: Toxic honey production is a
      significant risk in parts of New Zealand. Beekeepers and health professionals
      need to be informed of this risk and know how best to manage it. Due to this
      poisoning incident, public and professional awareness of honey poisoning has been
      substantially enhanced. This incident led to development of new food safety
      standards for New Zealand honey.

PMID- 29649199
TI  - The Otago Medical School Anatomy Museum Collection: Taonga for learning in the
      21st Century.

PMID- 29649200
TI  - Hypercalcemia in a bodybuilder with cosmetic silicone injections.
AB  - Granulomatous hypercalcemia due to silicone injections is a rare disease with
      scarce literature. We present a case of a 35-year-old Caucasian male bodybuilder
      with multiple silicone injections in his upper extremities who developed
      hypercalcemia and urinary symptoms. He necessitated two sessions of dialysis. A
      biopsy of the upper arm showed granulomatous tissue. Corticosteroids were
      administered to relieve symptoms and reverse laboratory abnormalities. Silicone
      induced hypercalcemia should be on high alert because of the increasing trend of
      body contour enhancements with injections, implants and fillers.

PMID- 29649201
TI  - Purulent facial lesion.

PMID- 29649202
TI  - If only Teina Pora had a MedicAlert bracelet.

PMID- 29649203
TI  - Permanent pacemaker implantation after cardiac surgery: rates, predictors and a
      novel risk score.

PMID- 29649204
TI  - Gnome medicine: what does genomic medicine mean to our patients and us?

PMID- 29649205
TI  - The paradoxical extinction of the most charismatic animals.
AB  - A widespread opinion is that conservation efforts disproportionately benefit
      charismatic species. However, this doesn't mean that they are not threatened, and
      which species are "charismatic" remains unclear. Here, we identify the 10 most
      charismatic animals and show that they are at high risk of imminent extinction in
      the wild. We also find that the public ignores these animals' predicament and we
      suggest it could be due to the observed biased perception of their abundance,
      based more on their profusion in our culture than on their natural populations.
      We hypothesize that this biased perception impairs conservation efforts because
      people are unaware that the animals they cherish face imminent extinction and do
      not perceive their urgent need for conservation. By freely using the image of
      rare and threatened species in their product marketing, many companies may
      participate in creating this biased perception, with unintended detrimental
      effects on conservation efforts, which should be compensated by channeling part
      of the associated profits to conservation. According to our hypothesis, this
      biased perception would be likely to last as long as the massive cultural and
      commercial presence of charismatic species is not accompanied by adequate
      information campaigns about the imminent threats they face.

PMID- 29649206
TI  - Eleven quick tips for finding research data.

PMID- 29649207
TI  - Physics-based simulations of aerial attacks by peregrine falcons reveal that
      stooping at high speed maximizes catch success against agile prey.
AB  - The peregrine falcon Falco peregrinus is renowned for attacking its prey from
      high altitude in a fast controlled dive called a stoop. Many other raptors employ
      a similar mode of attack, but the functional benefits of stooping remain obscure.
      Here we investigate whether, when, and why stooping promotes catch success, using
      a three-dimensional, agent-based modeling approach to simulate attacks of falcons
      on aerial prey. We simulate avian flapping and gliding flight using an analytical
      quasi-steady model of the aerodynamic forces and moments, parametrized by
      empirical measurements of flight morphology. The model-birds' flight control
      inputs are commanded by their guidance system, comprising a phenomenological
      model of its vision, guidance, and control. To intercept its prey, model-falcons
      use the same guidance law as missiles (pure proportional navigation); this
      assumption is corroborated by empirical data on peregrine falcons hunting lures.
      We parametrically vary the falcon's starting position relative to its prey,
      together with the feedback gain of its guidance loop, under differing assumptions
      regarding its errors and delay in vision and control, and for three different
      patterns of prey motion. We find that, when the prey maneuvers erratically, high
      altitude stoops increase catch success compared to low-altitude attacks, but only
      if the falcon's guidance law is appropriately tuned, and only given a high degree
      of precision in vision and control. Remarkably, the optimal tuning of the
      guidance law in our simulations coincides closely with what has been observed
      empirically in peregrines. High-altitude stoops are shown to be beneficial
      because their high airspeed enables production of higher aerodynamic forces for
      maneuvering, and facilitates higher roll agility as the wings are tucked, each of
      which is essential to catching maneuvering prey at realistic response delays.

PMID- 29649208
TI  - Assessing the durability and efficiency of landscape-based strategies to deploy
      plant resistance to pathogens.
AB  - Genetically-controlled plant resistance can reduce the damage caused by
      pathogens. However, pathogens have the ability to evolve and overcome such
      resistance. This often occurs quickly after resistance is deployed, resulting in
      significant crop losses and a continuing need to develop new resistant cultivars.
      To tackle this issue, several strategies have been proposed to constrain the
      evolution of pathogen populations and thus increase genetic resistance
      durability. These strategies mainly rely on varying different combinations of
      resistance sources across time (crop rotations) and space. The spatial scale of
      deployment can vary from multiple resistance sources occurring in a single
      cultivar (pyramiding), in different cultivars within the same field (cultivar
      mixtures) or in different fields (mosaics). However, experimental comparison of
      the efficiency (i.e. ability to reduce disease impact) and durability (i.e.
      ability to limit pathogen evolution and delay resistance breakdown) of landscape
      scale deployment strategies presents major logistical challenges. Therefore, we
      developed a spatially explicit stochastic model able to assess the
      epidemiological and evolutionary outcomes of the four major deployment options
      described above, including both qualitative resistance (i.e. major genes) and
      quantitative resistance traits against several components of pathogen
      aggressiveness: infection rate, latent period duration, propagule production
      rate, and infectious period duration. This model, implemented in the R package
      landsepi, provides a new and useful tool to assess the performance of a wide
      range of deployment options, and helps investigate the effect of landscape,
      epidemiological and evolutionary parameters. This article describes the model and
      its parameterisation for rust diseases of cereal crops, caused by fungi of the
      genus Puccinia. To illustrate the model, we use it to assess the epidemiological
      and evolutionary potential of the combination of a major gene and different
      traits of quantitative resistance. The comparison of the four major deployment
      strategies described above will be the objective of future studies.

PMID- 29649210
TI  - Ten simple rules for responsible referencing.

PMID- 29649209
TI  - Gene duplicates cause hybrid lethality between sympatric species of Mimulus.
AB  - Hybrid incompatibilities play a critical role in the evolution and maintenance of
      species. We have discovered a simple genetic incompatibility that causes
      lethality in hybrids between two closely related species of yellow monkeyflower
      (Mimulus guttatus and M. nasutus). This hybrid incompatibility, which causes one
      sixteenth of F2 hybrid seedlings to lack chlorophyll and die shortly after
      germination, occurs between sympatric populations that are connected by ongoing
      interspecific gene flow. Using complimentary genetic mapping and gene expression
      analyses, we show that lethality occurs in hybrids that lack a functional copy of
      the critical photosynthetic gene pTAC14. In M. guttatus, this gene was
      duplicated, but the ancestral copy is no longer expressed. In M. nasutus, the
      duplication is missing altogether. As a result, hybrids die when they are
      homozygous for the nonfunctional M. guttatus copy and missing the duplicate from
      M. nasutus, apparently due to misregulated transcription of key photosynthetic
      genes. Our study indicates that neutral evolutionary processes may play an
      important role in the evolution of hybrid incompatibilities and opens the door to
      direct investigations of their contribution to reproductive isolation among
      naturally hybridizing species.

PMID- 29649211
TI  - Stable centrosomal roots disentangle to allow interphase centriole independence.
AB  - The centrosome is a non-membrane-bound cellular compartment consisting of 2
      centrioles surrounded by a protein coat termed the pericentriolar material (PCM).
      Centrioles generally remain physically associated together (a phenomenon called
      centrosome cohesion), yet how this occurs in the absence of a bounding lipid
      membrane is unclear. One model posits that pericentriolar fibres formed from
      rootletin protein directly link centrioles, yet little is known about the
      structure, biophysical properties, or assembly kinetics of such fibres. Here, I
      combine live-cell imaging of endogenously tagged rootletin with cell fusion and
      find previously unrecognised plasticity in centrosome cohesion. Rootletin forms
      large, diffusionally stable bifurcating fibres, which amass slowly on mature
      centrioles over many hours from anaphase. Nascent centrioles (procentrioles), in
      contrast, do not form roots and must be licensed to do so through polo-like
      kinase 1 (PLK1) activity. Transient separation of roots accompanies centriolar
      repositioning during the interphase, suggesting that centrioles organize as
      independent units, each containing discrete roots. Indeed, forced induction of
      duplicate centriole pairs allows independent reshuffling of individual centrioles
      between the pairs. Therefore collectively, these findings suggest that
      progressively nucleated polymers mediate the dynamic association of centrioles as
      either 1 or 2 interphase centrosomes, with implications for the understanding of
      how non-membrane-bound organelles self-organise.

PMID- 29649212
TI  - Principles that govern competition or co-existence in Rho-GTPase driven
      polarization.
AB  - Rho-GTPases are master regulators of polarity establishment and cell morphology.
      Positive feedback enables concentration of Rho-GTPases into clusters at the cell
      cortex, from where they regulate the cytoskeleton. Different cell types
      reproducibly generate either one (e.g. the front of a migrating cell) or several
      clusters (e.g. the multiple dendrites of a neuron), but the mechanistic basis for
      unipolar or multipolar outcomes is unclear. The design principles of Rho-GTPase
      circuits are captured by two-component reaction-diffusion models based on
      conserved aspects of Rho-GTPase biochemistry. Some such models display rapid
      winner-takes-all competition between clusters, yielding a unipolar outcome. Other
      models allow prolonged co-existence of clusters. We investigate the behavior of a
      simple class of models and show that while the timescale of competition varies
      enormously depending on model parameters, a single factor explains a large
      majority of this variation. The dominant factor concerns the degree to which the
      maximal active GTPase concentration in a cluster approaches a "saturation point"
      determined by model parameters. We suggest that both saturation and the effect of
      saturation on competition reflect fundamental properties of the Rho-GTPase
      polarity machinery, regardless of the specific feedback mechanism, which predict
      whether the system will generate unipolar or multipolar outcomes.

PMID- 29649214
TI  - When genes move, genomes collide.

PMID- 29649213
TI  - New insights into the transposition mechanisms of IS6110 and its dynamic
      distribution between Mycobacterium tuberculosis Complex lineages.
AB  - The insertion Sequence IS6110, only present in the pathogens of the Mycobacterium
      tuberculosis Complex (MTBC), has been the gold-standard epidemiological marker
      for TB for more than 25 years, but biological implications of IS6110
      transposition during MTBC adaptation to humans remain elusive. By studying 2,236
      clinical isolates typed by IS6110-RFLP and covering the MTBC, we remarked a
      lineage-specific content of IS6110 being higher in modern globally distributed
      strains. Once observed the IS6110 distribution in the MTBC, we selected
      representative isolates and found a correlation between the normalized expression
      of IS6110 and its abundance in MTBC chromosomes. We also studied the molecular
      regulation of IS6110 transposition and we found a synergistic action of two post
      transcriptional mechanisms: a -1 ribosomal frameshift and a RNA pseudoknot which
      interferes translation. The construction of a transcriptionally active
      transposase resulted in 20-fold increase of the transposition frequency. Finally,
      we examined transposition in M. bovis and M. tuberculosis during laboratory
      starvation and in a mouse infection model of TB. Our results shown a higher
      transposition in M. tuberculosis, that preferably happens during TB infection in
      mice and after one year of laboratory culture, suggesting that IS6110
      transposition is dynamically adapted to the host and to adverse growth
      conditions.

PMID- 29649215
TI  - Mobile phone specific electromagnetic fields induce transient DNA damage and
      nucleotide excision repair in serum-deprived human glioblastoma cells.
AB  - Some epidemiological studies indicate that the use of mobile phones causes cancer
      in humans (in particular glioblastomas). It is known that DNA damage plays a key
      role in malignant transformation; therefore, we investigated the impact of the
      UMTS signal which is widely used in mobile telecommunications, on DNA stability
      in ten different human cell lines (six brain derived cell lines, lymphocytes,
      fibroblasts, liver and buccal tissue derived cells) under conditions relevant for
      users (SAR 0.25 to 1.00 W/kg). We found no evidence for induction of damage in
      single cell gel electrophoresis assays when the cells were cultivated with serum.
      However, clear positive effects were seen in a p53 proficient glioblastoma line
      (U87) when the cells were grown under serum free conditions, while no effects
      were found in p53 deficient glioblastoma cells (U251). Further experiments showed
      that the damage disappears rapidly in U87 and that exposure induced nucleotide
      excision repair (NER) and does not cause double strand breaks (DSBs). The
      observation of NER induction is supported by results of a proteome analysis
      indicating that several proteins involved in NER are up-regulated after exposure
      to UMTS; additionally, we found limited evidence for the activation of the gamma
      interferon pathway. The present findings show that the signal causes transient
      genetic instability in glioma derived cells and activates cellular defense
      systems.

PMID- 29649216
TI  - Serum microRNA profiles in athyroid patients on and off levothyroxine therapy.
AB  - BACKGROUND: Levothyroxine replacement treatment in hypothyroidism is unable to
      restore physiological thyroxine and triiodothyronine concentrations in serum and
      tissues completely. Normal serum thyroid stimulating hormone (TSH) concentrations
      reflect only pituitary euthyroidism and, therefore, novel biomarkers representing
      tissue-specific thyroid state are needed. MicroRNAs (miRNAs), small non-coding
      regulatory RNAs, exhibit tissue-specific expression patterns and can be
      detectable in serum. Previous studies have demonstrated differential expression
      of (precursors of) miRNAs in tissues under the influence of thyroid hormone.
      OBJECTIVE: To study if serum miRNA profiles are changed in different thyroid
      states. DESIGN AND METHODS: We studied 13 athyroid patients (6 males) during TSH
      suppressive therapy and after 4 weeks of thyroid hormone withdrawal. A magnetic
      bead capture system was used to isolate 384 defined miRNAs from serum.
      Subsequently, the TaqMan Array Card 3.0 platform was used for profiling after
      individual target amplification. RESULTS: Mean age of the subjects was 44.0 years
      (range 20-61 years). Median TSH levels were 88.9 mU/l during levothyroxine
      withdrawal and 0.006 mU/l during LT4 treatment with a median dosage of 2.1
      MUg/kg. After normalization to allow inter-sample analysis, a paired analysis did
      not demonstrate a significant difference in expression of any of the 384 miRNAs
      analyzed on and off LT4 treatment. CONCLUSION: Although we previously showed an
      up-regulation of pri-miRNAs 133b and 206 in hypothyroid state in skeletal muscle,
      the present study does not supply evidence that thyroid state also affects serum
      miRNAs in humans.

PMID- 29649219
TI  - Stone heterogeneity index on single-energy noncontrast computed tomography can be
      a positive predictor of urinary stone composition.
AB  - The aim of this study was to investigate the correlation between stone
      composition and single-energy noncontrast computed tomography (NCCT) parameters,
      including stone heterogeneity index (SHI) and mean stone density (MSD), in
      patients with urinary calculi. We retrospectively reviewed medical records of 255
      patients who underwent operations or procedures for urinary stones or had
      spontaneous stone passage between December 2014 and October 2015. Among these,
      214 patients with urinary calculi who underwent NCCT and stone composition
      analyses were included in the study. Maximal stone length (MSL), mean stone
      density (MSD), and stone heterogeneity index (SHI) were determined on
      pretreatment NCCT. The mean MSD (454.68+/-177.80 HU) and SHI (115.82+/-96.31 HU)
      of uric acid stones were lower than those of all other types. Based on post hoc
      tests, MSD was lower for uric acid stones than for the other types (vs. CaOx:
      P<0.001; vs. infection stones: P<0.001). SHI was lower for uric acid stones than
      for the other types (vs. CaOx: P<0.001; vs. infection stones: P<0.001) Receiver
      operating characteristic curves of uric acid stones for MSD and SHI demonstrated
      that SHI (cut-off value: 140.4 HU) was superior to MSD (cut-off value: 572.3 HU)
      in predicting uric acid stones (P<0.001).

PMID- 29649217
TI  - The UBR-1 ubiquitin ligase regulates glutamate metabolism to generate coordinated
      motor pattern in Caenorhabditis elegans.
AB  - UBR1 is an E3 ubiquitin ligase best known for its ability to target protein
      degradation by the N-end rule. The physiological functions of UBR family
      proteins, however, remain not fully understood. We found that the functional loss
      of C. elegans UBR-1 leads to a specific motor deficit: when adult animals
      generate reversal movements, A-class motor neurons exhibit synchronized
      activation, preventing body bending. This motor deficit is rescued by removing
      GOT-1, a transaminase that converts aspartate to glutamate. Both UBR-1 and GOT-1
      are expressed and critically required in premotor interneurons of the reversal
      motor circuit to regulate the motor pattern. ubr-1 and got-1 mutants exhibit
      elevated and decreased glutamate level, respectively. These results raise an
      intriguing possibility that UBR proteins regulate glutamate metabolism, which is
      critical for neuronal development and signaling.

PMID- 29649220
TI  - Statistical reporting inconsistencies in experimental philosophy.
AB  - Experimental philosophy (x-phi) is a young field of research in the intersection
      of philosophy and psychology. It aims to make progress on philosophical questions
      by using experimental methods traditionally associated with the psychological and
      behavioral sciences, such as null hypothesis significance testing (NHST).
      Motivated by recent discussions about a methodological crisis in the behavioral
      sciences, questions have been raised about the methodological standards of x-phi.
      Here, we focus on one aspect of this question, namely the rate of inconsistencies
      in statistical reporting. Previous research has examined the extent to which
      published articles in psychology and other behavioral sciences present
      statistical inconsistencies in reporting the results of NHST. In this study, we
      used the R package statcheck to detect statistical inconsistencies in x-phi, and
      compared rates of inconsistencies in psychology and philosophy. We found that
      rates of inconsistencies in x-phi are lower than in the psychological and
      behavioral sciences. From the point of view of statistical reporting consistency,
      x-phi seems to do no worse, and perhaps even better, than psychological science.

PMID- 29649218
TI  - Global characterization of copy number variants in epilepsy patients from whole
      genome sequencing.
AB  - Epilepsy will affect nearly 3% of people at some point during their lifetime.
      Previous copy number variants (CNVs) studies of epilepsy have used array-based
      technology and were restricted to the detection of large or exonic events. In
      contrast, whole-genome sequencing (WGS) has the potential to more comprehensively
      profile CNVs but existing analytic methods suffer from limited accuracy. We show
      that this is in part due to the non-uniformity of read coverage, even after intra
      sample normalization. To improve on this, we developed PopSV, an algorithm that
      uses multiple samples to control for technical variation and enables the robust
      detection of CNVs. Using WGS and PopSV, we performed a comprehensive
      characterization of CNVs in 198 individuals affected with epilepsy and 301
      controls. For both large and small variants, we found an enrichment of rare
      exonic events in epilepsy patients, especially in genes with predicted loss-of
      function intolerance. Notably, this genome-wide survey also revealed an
      enrichment of rare non-coding CNVs near previously known epilepsy genes. This
      enrichment was strongest for non-coding CNVs located within 100 Kbp of an
      epilepsy gene and in regions associated with changes in the gene expression, such
      as expression QTLs or DNase I hypersensitive sites. Finally, we report on 21
      potentially damaging events that could be associated with known or new candidate
      epilepsy genes. Our results suggest that comprehensive sequence-based profiling
      of CNVs could help explain a larger fraction of epilepsy cases.

PMID- 29649222
TI  - Detecting hierarchical levels of connectivity in a population of Acacia tortilis
      at the northern edge of the species' global distribution: Combining classical
      population genetics and network analyses.
AB  - Genetic diversity and structure of populations at the edge of the species'
      spatial distribution are important for potential adaptation to environmental
      changes and consequently, for the long-term survival of the species. Here, we
      combined classical population genetic methods with newly developed network
      analyses to gain complementary insights into the genetic structure and diversity
      of Acacia tortilis, a keystone desert tree, at the northern edge of its global
      distribution, where the population is under threat from climatic, ecological, and
      anthropogenic changes. We sampled A. tortilis from 14 sites along the Dead Sea
      region and the Arava Valley in Israel and in Jordan. In addition, we obtained
      samples from Egypt and Sudan, the hypothesized origin of the species. Samples
      from all sites were genotyped using six polymorphic microsatellite loci.Our
      results indicate a significant genetic structure in A. tortilis along the Arava
      Valley. This was detected at different hierarchical levels-from the basic unit of
      the subpopulation, corresponding to groups of trees within ephemeral rivers
      (wadis), to groups of subpopulations (communities) that are genetically more
      connected relative to others. The latter structure mostly corresponds to the
      partition of the major drainage basins in the area. Network analyses, combined
      with classical methods, allowed for the identification of key A. tortilis
      subpopulations in this region, characterized by their relatively high level of
      genetic diversity and centrality in maintaining gene flow in the population.
      Characterizing such key subpopulations may enable conservation managers to focus
      their efforts on certain subpopulations that might be particularly important for
      the population's long-term persistence, thus contributing to species conservation
      within its peripheral range.

PMID- 29649221
TI  - Long-acting insulin analogues for type 1 diabetes: An overview of systematic
      reviews and meta-analysis of randomized controlled trials.
AB  - BACKGROUND: The comparison between long acting insulin analogues (LAIA) and human
      insulin (NPH) has been investigated for decades, with many randomized controlled
      trials (RCTs) and systematic reviews giving mixed results. This overlapping and
      contradictory evidence has increased uncertainty on coverage decisions at health
      systems level. AIM: To conduct an overview of systematic reviews and update
      existing reviews, preparing new meta-analysis to determine whether LAIA are
      effective for T1D patients compared to NPH. METHODS: We identified systematic
      reviews of RCTs that evaluated the efficacy of LAIA glargine or detemir, compared
      to NPH insulin for T1D, assessing glycated hemoglobin (A1C) and hypoglycemia.
      Data sources included Pubmed, Cochrane Library, EMBASE and hand-searching. The
      methodological quality of studies was independently assessed by two reviewers,
      using AMSTAR and Jadad scale. We found 11 eligible systematic reviews that
      contained a total of 25 relevant clinical trials. Two reviewers independently
      abstracted data. RESULTS: We found evidence that LAIA are efficacious compared to
      NPH, with estimates showing a reduction in nocturnal hypoglycemia episodes (RR
      0.66; 95% CI 0.57; 0.76) and A1C (95% CI 0.23; 0.12). No significance was found
      related to severe hypoglycemia (RR 0.94; 95% CI 0.71; 1.24). CONCLUSION: This
      study design has allowed us to carry out the most comprehensive assessment of
      RCTs on this subject, filling a gap in diabetes research. Our paper addresses a
      question that is important not only for decision makers but also for clinicians.

PMID- 29649223
TI  - Niosomes, an alternative for liposomal delivery.
AB  - Niosomes are used in studies for drug delivery or gene transfer. However, their
      physical properties and features relative to liposomes are not well documented.
      To characterize and more rationally optimize niosome formulations, the properties
      of these vesicle systems are compared to those of liposomes composed of
      phosphatidylcholine and phosphatidylethanolamine lipids plus cholesterol.
      Niosomes are highly stable and only slightly more leaky than liposomes as assayed
      by calcein leakage; the permeability for ions (KCl) is higher than that of
      liposomes. Contrary to liposomes, the size of niosomes decreases substantially
      upon freezing in liquid nitrogen and subsequent thawing, as shown by cryo-EM and
      dynamic light scattering. The packing of niosomal membranes was determined by
      laurdan fluorescence and is slightly lower than that of liposomes. We did not
      succeed in the functional reconstitution of the L-arginine/L-ornithine antiporter
      ArcD2 in niosomes, which we attribute to the non-ionic nature of the surfactants.
      The antimicrobial peptides alamethicin and melittin act similarly on niosomes and
      liposomes composed of unsaturated components, whereas both niosomes and liposomes
      are unaffected when saturated amphiphiles are used. In conclusion, in terms of
      stability and permeability for drug-size molecules niosomes are comparable to
      liposomes and they may offer an excellent, inexpensive alternative for delivery
      purposes.

PMID- 29649224
TI  - Seasonal asthma in Melbourne, Australia, and some observations on the occurrence
      of thunderstorm asthma and its predictability.
AB  - We examine the seasonality of asthma-related hospital admissions in Melbourne,
      Australia, in particular the contribution and predictability of episodic
      thunderstorm asthma. Using a time-series ecological approach based on asthma
      admissions to Melbourne metropolitan hospitals, we identified seasonal peaks in
      asthma admissions that were centred in late February, June and mid-November.
      These peaks were most likely due to the return to school, winter viral infections
      and seasonal allergies, respectively. We performed non-linear statistical
      regression to predict daily admission rates as functions of the seasonal cycle,
      weather conditions, reported thunderstorms, pollen counts and air quality.
      Important predictor variables were the seasonal cycle and mean relative humidity
      in the preceding two weeks, with higher humidity associated with higher asthma
      admissions. Although various attempts were made to model asthma admissions, none
      of the models explained substantially more variation above that associated with
      the annual cycle. We also identified a list of high asthma admissions days
      (HAADs). Most HAADs fell in the late-February return-to-school peak and the
      November allergy peak, with the latter containing the greatest number of daily
      admissions. Many HAADs in the spring allergy peak may represent episodes of
      thunderstorm asthma, as they were associated with rainfall, thunderstorms, high
      ambient grass pollen levels and high humidity, a finding that suggests
      thunderstorm asthma is a recurrent phenomenon in Melbourne that occurs roughly
      once per five years. The rarity of thunderstorm asthma events makes prediction
      challenging, underscoring the importance of maintaining high standards of asthma
      management, both for patients and health professionals, especially during late
      spring and early summer.

PMID- 29649225
TI  - Insulin receptor knockdown blocks filarial parasite development and alters egg
      production in the southern house mosquito, Culex quinquefasciatus.
AB  - Lymphatic filariasis, commonly known as elephantiasis, is a painful and
      profoundly disfiguring disease. Wuchreria bancrofti (Wb) is responsible for >90%
      of infections and the remainder are caused by Brugia spp. Mosquitoes of the
      genera Culex (in urban and semi-urban areas), Anopheles (in rural areas of Africa
      and elsewhere), and Aedes (in Pacific islands) are the major vectors of W.
      bancrofti. A preventive chemotherapy called mass drug administration (MDA),
      including albendazole with ivermectin or diethylcarbamazine citrate (DEC) is used
      in endemic areas. Vector control strategies such as residual insecticide spraying
      and long-lasting insecticidal nets are supplemental to the core strategy of MDA
      to enhance elimination efforts. However, increasing insecticide resistance in
      mosquitoes and drug resistance in parasite limit the effectiveness of existing
      interventions, and new measures are needed for mosquito population control and
      disruption of mosquito-parasite interactions to reduce transmission. Mosquito
      insulin signaling regulates nutrient metabolism and has been implicated in
      reduced prevalence and intensity of malaria parasite, Plasmodium falciparum,
      infection in mosquitoes. Currently no data are available to assess how insulin
      signaling in mosquitoes affects the development of multi-cellular parasites, such
      as filarial nematodes. Here, we show that insulin receptor knockdown in blood fed
      C. quinquefasciatus, the major vector of Wb in India, completely blocks the
      development of filarial nematode parasite to the infective L3 stage, and results
      in decreased ecdysteroid production and trypsin activity leading to fewer
      mosquito eggs. These data indicate that a functional mosquito insulin receptor
      (IR) is necessary for filarial parasite development and mosquito reproduction.
      Therefore, insulin signaling may represent a new target for the development of
      vector control or parasite blocking strategies.

PMID- 29649226
TI  - Assessing the efficacy of fathead minnows (Pimephales promelas) for mosquito
      control.
AB  - Mosquitoes function as important vectors for many diseases globally and can have
      substantial negative economic, environmental, and health impacts. Specifically,
      West Nile virus (WNv) is a significant and increasing threat to wildlife
      populations and human health throughout North America. Mosquito control is an
      important means of controlling the spread of WNv, as the virus is primarily
      spread between avian and mosquito vectors. This is of particular concern for
      avian host species such as the Greater sage-grouse (Centrocercus urophasianus),
      in which WNv negatively impacts fitness parameters. Most mosquito control methods
      focus on the larval stages. In North America, control efforts are largely limited
      to larvicides, which require repeated application and have potentially negative
      ecological impacts. There are multiple potential advantages to using indigenous
      fish species as an alternative for larval control including lowered environmental
      impact, decreased costs in terms of time and financial inputs, and the potential
      for the establishment of self-sustaining fish populations. We tested the efficacy
      of using fathead minnows (Pimephales promelas) as biological control for mosquito
      populations in livestock reservoirs of semiarid rangelands. We introduced minnows
      into 10 treatment reservoirs and monitored an additional 6 non-treated reservoirs
      as controls over 3 years. Adult mosquitoes of species known to transmit WNv
      (e.g., Culex tarsalis) were captured at each site and mosquito larvae were also
      present at all sites. Stable isotope analysis confirmed that introduced fathead
      minnows were feeding at the mosquito larvae trophic level in all but one
      treatment pond. Treatment ponds demonstrated suppressed levels of mosquito larva
      over each season compared to controls with a model-predicted 114% decrease in
      larva density within treatment ponds. Minnows established self-sustaining
      populations throughout the study in all reservoirs that maintained sufficient
      water levels. Minnow survival was not influenced by water quality. Though minnows
      did not completely eradicate mosquito larvae, minnows are a promising alternative
      to controlling mosquito larvae density within reservoirs. We caution that careful
      site selection is critical to avoid potential negative impacts, but suggest the
      introduction of fathead minnows in reservoirs can dramatically reduce mosquito
      larva abundance and potentially help mitigate vector-borne disease transmission.

PMID- 29649227
TI  - From kitchen to classroom: Assessing the impact of cleaner burning biomass
      fuelled cookstoves on primary school attendance in Karonga district, northern
      Malawi.
AB  - Household air pollution from burning solid fuels is responsible for an estimated
      2.9 million premature deaths worldwide each year and 4.5% of global disability
      adjusted life years, while cooking and fuel collection pose a considerable time
      burden, particularly for women and children. Cleaner burning biomass-fuelled
      cookstoves have the potential to lower exposure to household air pollution as
      well as reduce fuelwood demand by increasing the combustion efficiency of cooking
      fires, which may in turn yield ancillary benefits in other domains. The present
      paper capitalises on opportunities offered by the Cooking and Pneumonia Study
      (CAPS), the largest randomised trial of biomass-fuelled cookstoves on health
      outcomes conducted to date, the design of which allows for the evaluation of
      additional outcomes at scale. This mixed methods study assesses the impact of
      cookstoves on primary school absenteeism in Karonga district, northern Malawi, in
      particular by conferring health and time and resource gains on young people aged
      5-18. The analysis combines quantitative data from 6168 primary school students
      with in-depth interviews and focus group discussions carried out among 48
      students in the same catchment area in 2016. Negative binomial regression models
      find no evidence that the cookstoves affected primary school absenteeism overall
      [IRR 0.92 (0.71-1.18), p = 0.51]. Qualitative analysis suggests that the
      cookstoves did not sufficiently improve household health to influence school
      attendance, while the time and resource burdens associated with cooking
      activities-although reduced in intervention households-were considered to be
      compatible with school attendance in both trial arms. More research is needed to
      assess whether the cookstoves influenced educational outcomes not captured by the
      attendance measure available, such as timely arrival to school or hours spent on
      homework.

PMID- 29649228
TI  - An intragenic approach to confer glyphosate resistance in chile (Capsicum annuum)
      by introducing an in vitro mutagenized chile EPSPS gene encoding for a glyphosate
      resistant EPSPS protein.
AB  - Chile pepper (Capsicum annuum) is an important high valued crop worldwide, and
      when grown on a large scale has problems with weeds. One important herbicide used
      is glyphosate. Glyphosate inactivates the enzyme 5-enolpyruvylshikimate-3
      phosphate synthase (EPSPS), a key enzyme in the synthesis of aromatic amino
      acids. A transgenic approach towards making glyphosate resistant plants, entails
      introducing copies of a gene encoding for glyphosate-resistant EPSPS enzyme into
      the plant. The main objective of our work was to use an intragenic approach to
      confer resistance to glyphosate in chile which would require using only chile
      genes for transformation including the selectable marker. Tobacco was used as the
      transgenic system to identify different gene constructs that would allow for the
      development of the intragenic system for chile, since chile transformation is
      inefficient. An EPSPS gene was isolated from chile and mutagenized to introduce
      substitutions that are known to make the encoded enzyme resistant to glyphosate.
      The promoter for EPSPS gene was isolated from chile and the mutagenized chile
      EPSPS cDNA was engineered behind both the CaMV35S promoter and the EPSPS
      promoter. The leaves from the transformants were checked for resistance to
      glyphosate using a cut leaf assay. In tobacco, though both gene constructs
      exhibited some degree of resistance to glyphosate, the construct with the CaMV35S
      promoter was more effective and as such chile was transformed with this gene
      construct. The chile transformants showed resistance to low concentrations of
      glyphosate. Furthermore, preliminary studies showed that the mutated EPSPS gene
      driven by the CaMV35S promoter could be used as a selectable marker for
      transformation. We have shown that an intragenic approach can be used to confer
      glyphosate-resistance in chile. However, we need a stronger chile promoter and a
      mutated chile gene that encodes for a more glyphosate resistant EPSPS protein.

PMID- 29649229
TI  - Association between perceived social support and induced abortion: A study in
      maternal health centers in Lima, Peru.
AB  - OBJECTIVES: This study aimed to assess the association between perceived social
      support and induced abortion among young women in Lima, Peru. In addition,
      prevalence and incidence of induced abortion was estimated. METHODS/PRINCIPAL
      FINDINGS: A cross-sectional study enrolling women aged 18-25 years from maternal
      health centers in Southern Lima, Peru, was conducted. Induced abortion was
      defined as the difference between the total number of pregnancies ended in
      abortion and the number of spontaneous abortions; whereas perceived social
      support was assessed using the DUKE-UNC scale. Prevalence and incidence of
      induced abortion (per 100 person-years risk) was estimated, and the association
      of interest was evaluated using Poisson regression models with robust variance. A
      total of 298 women were enrolled, mean age 21.7 (+/- 2.2) years. Low levels of
      social support were found in 43.6% (95%CI 38.0%-49.3%), and 17.4% (95%CI: 13.1%-
      21.8%) women reported at least one induced abortion. The incidence of induced
      abortion was 2.37 (95%CI: 1.81-3.11) per 100 person-years risk. The multivariable
      model showed evidence of the association between low perceived social support and
      induced abortion (RR = 1.94; 95%CI: 1.14-3.30) after controlling for confounders.
      CONCLUSIONS: There was evidence of an association between low perceived social
      support and induced abortion among women aged 18 to 25 years. Incidence of
      induced abortion was similar or even greater than rates of countries where
      abortion is legal. Strategies to increase social support and reduce induced
      abortion rates are needed.

PMID- 29649230
TI  - Lower serum IgA is associated with COPD exacerbation risk in SPIROMICS.
AB  - BACKGROUND: Decreased but measurable serum IgA levels (<=70 mg/dL) have been
      associated with risk for infections in some populations, but are unstudied in
      COPD. This study tested the hypothesis that subnormal serum IgA levels would be
      associated with exacerbation risk in COPD. METHODS: Data were analyzed from 1,049
      COPD participants from the observational cohort study SPIROMICS (535 (51%) women;
      mean age 66.1 (SD 7.8), 338 (32%) current smokers) who had baseline serum IgA
      measured using the Myriad RBM biomarker discovery platform. Exacerbation data was
      collected prospectively (mean 944.3 (SD 281.3) days), and adjusted linear,
      logistic and zero-inflated negative binomial regressions were performed. RESULTS:
      Mean IgA was 269.1 mg/dL (SD 150.9). One individual had deficient levels of serum
      IgA (<7 mg/dL) and 25 (2.4%) had IgA level <=70 mg/dL. Participants with IgA <=70
      mg/dL were younger (62 vs. 66 years, p = 0.01) but otherwise similar to those
      with higher IgA. In adjusted models, IgA <=70 mg/dL was associated with higher
      exacerbation incidence rates (IRR 1.71, 95% CI 1.01-2.87, p = 0.044) and greater
      risk for any severe exacerbation (OR 2.99, 95% CI 1.30-6.94, p = 0.010). In
      adjusted models among those in the lowest decile (<120 mg/dL), each 10 mg/dL
      decrement in IgA (analyzed continuously) was associated with more exacerbations
      during follow-up (beta 0.24, 95% CI 0.017-0.46, p = 0.035). CONCLUSIONS:
      Subnormal serum IgA levels were associated with increased risk for acute
      exacerbations, supporting mildly impaired IgA levels as a contributing factor in
      COPD morbidity. Additionally, a dose-response relationship between lower serum
      IgA and number of exacerbations was found among individuals with serum IgA in the
      lowest decile, further supporting the link between serum IgA and exacerbation
      risk. Future COPD studies should more comprehensively characterize immune status
      to define the clinical relevance of these findings and their potential for
      therapeutic correction.

PMID- 29649232
TI  - The experience of discrimination of individuals living with chronic hepatitis B
      in four provinces of China.
AB  - OBJECTIVES: To assess chronic hepatitis B (CHB) patients' knowledge about
      hepatitis B and their experience of discrimination with regard to study, work,
      and daily life. METHODS: We administered a questionnaire to 797 CHB patients in
      four provinces of China and used one-way analysis of variance (ANOVA) and a
      generalized linear model (GLM) to identify factors associated with
      discrimination. RESULTS: CHB patients had low levels of knowledge about hepatitis
      B. Patients under 40 years of age with a junior college education or above knew
      more about hepatitis B than CHB patients over 40 years of age who had only a high
      school education. Three-fourths of patients had experienced discrimination
      because of their hepatitis B infection, with no differences in the proportion
      experiencing discrimination by sex or age. People with more education reported
      less discrimination. Patients in Beijing and Henan province perceived less
      discrimination than those in Shaanxi and Guangdong provinces. Discrimination was
      significantly associated with negative emotions. CHB patients had little
      awareness of China's anti-discrimination laws and policies. Among patients who
      had experienced discrimination, fewer than 10% knew organizations or institutions
      that could offer help. Over 60% of CHB patients who experienced discrimination
      chose not to respond. CONCLUSION: CHB patients in China commonly experienced
      discrimination, which was associated with significant, negative emotional stress.
      To mitigate the damaging effects of discrimination, our study suggests raising
      general population knowledge about hepatitis B, raising awareness of the
      availability of legal protection and organizations that can fight discrimination,
      and providing psychological support for CHB patients.

PMID- 29649231
TI  - Application of quality by design for 3D printed bone prostheses and scaffolds.
AB  - 3D printing is an emergent manufacturing technology recently being applied in the
      medical field for the development of custom bone prostheses and scaffolds.
      However, successful industry transformation to this new design and manufacturing
      approach requires technology integration, concurrent multi-disciplinary
      collaboration, and a robust quality management framework. This latter change
      enabler is the focus of this study. While a number of comprehensive quality
      frameworks have been developed in recent decades to ensure that the manufacturing
      of medical devices produces reliable products, they are centred on the
      traditional context of standardised manufacturing techniques. The advent of 3D
      printing technologies and the prospects for mass customisation provides
      significant market opportunities, but also presents a serious challenge to
      regulatory bodies tasked with managing and assuring product quality and safety.
      Before 3D printing bone prostheses and scaffolds can gain traction, industry
      stakeholders, such as regulators, clients, medical practitioners, insurers,
      lawyers, and manufacturers, would all require a high degree of confidence that
      customised manufacturing can achieve the same quality outcomes as standardised
      manufacturing. A Quality by Design (QbD) approach to custom 3D printed prostheses
      can help to ensure that products are designed and manufactured correctly from the
      beginning without errors. This paper reports on the adaptation of the QbD
      approach for the development process of 3D printed custom bone prosthesis and
      scaffolds. This was achieved through the identification of the Critical Quality
      Attributes of such products, and an extensive review of different design and
      fabrication methods for 3D printed bone prostheses. Research outcomes include the
      development of a comprehensive design and fabrication process flow diagram, and
      categorised risks associated with the design and fabrication processes of such
      products. An extensive systematic literature review and post-hoc evaluation
      survey with experts was completed to evaluate the likely effectiveness of the
      herein suggested QbD framework.

PMID- 29649233
TI  - Euglena gracilis growth and cell composition under different temperature, light
      and trophic conditions.
AB  - BACKGROUND: Euglena gracilis, a photosynthetic protist, produces protein,
      unsaturated fatty acids, wax esters, and a unique beta-1,3-glucan called
      paramylon, along with other valuable compounds. The cell composition of E.
      gracilis was investigated in this study to understand how light and organic
      carbon (photo-, mixo- and heterotrophic conditions) affected growth and cell
      composition (especially lipids). Comparisons were primarily carried out in
      cultures grown at 23  degrees C, but the effect of growth at higher temperatures
      (27 or 30  degrees C) was also considered. CELL GROWTH: Specific growth rates
      were slightly lower when E. gracilis was grown on glucose in either heterotrophic
      or mixotrophic conditions than when grown photoautotrophically, although the
      duration of exponential growth was longer. Temperature determined the rate of
      exponential growth in all cultures, but not the linear growth rate during light
      limited growth in phototrophic conditions. Temperature had less effect on cell
      composition. CELL COMPOSITION: Although E. gracilis was not expected to store
      large amounts of paramylon when grown phototrophically, we observed that
      phototrophic cells could contain up to 50% paramylon. These cells contained up to
      33% protein and less than 20% lipophilic compounds, as expected. The biomass
      contained about 8% fatty acids (measured as fatty acid methyl esters), most of
      which were unsaturated. The fatty acid content of cells grown in mixotrophic
      conditions was similar to that observed in phototrophic cells, but was lower in
      cells grown heterotrophically. Heterotrophic cells contained less unsaturated
      fatty acids than phototrophic or mixotrophic cells. alpha-Linolenic acid was
      present at 5 to 18 mg g-1 dry biomass in cells grown in the presence of light,
      but at < 0.5 mg g-1 biomass in cells grown in the dark. Eicosapentaenoic and
      docosahexaenoic acids were detected at 1 to 5 mg g-1 biomass. Light was also
      important for the production of vitamin E and phytol.

PMID- 29649234
TI  - Reliability, minimal detectable change and responsiveness to change: Indicators
      to select the best method to measure sedentary behaviour in older adults in
      different study designs.
AB  - INTRODUCTION: Prolonged sedentary behaviour (SB) is associated with poor health.
      It is unclear which SB measure is most appropriate for interventions and
      population surveillance to measure and interpret change in behaviour in older
      adults. The aims of this study: to examine the relative and absolute reliability,
      Minimal Detectable Change (MDC) and responsiveness to change of subjective and
      objective methods of measuring SB in older adults and give recommendations of use
      for different study designs. METHODS: SB of 18 older adults (aged 71 (IQR 7)
      years) was assessed using a systematic set of six subjective tools, derived from
      the TAxonomy of Self report Sedentary behaviour Tools (TASST), and one objective
      tool (activPAL3c), over 14 days. Relative reliability (Intra Class Correlation
      coefficients-ICC), absolute reliability (SEM), MDC, and the relative
      responsiveness (Cohen's d effect size (ES) and Guyatt's Responsiveness
      coefficient (GR)) were calculated for each of the different tools and ranked for
      different study designs. RESULTS: ICC ranged from 0.414 to 0.946, SEM from 36.03
      to 137.01 min, MDC from 1.66 to 8.42 hours, ES from 0.017 to 0.259 and GR from
      0.024 to 0.485. Objective average day per week measurement ranked as most
      responsive in a clinical practice setting, whereas a one day measurement ranked
      highest in quasi-experimental, longitudinal and controlled trial study designs.
      TV viewing-Previous Week Recall (PWR) ranked as most responsive subjective
      measure in all study designs. CONCLUSIONS: The reliability, Minimal Detectable
      Change and responsiveness to change of subjective and objective methods of
      measuring SB is context dependent. Although TV viewing-PWR is the more reliable
      and responsive subjective method in most situations, it may have limitations as a
      reliable measure of total SB. Results of this study can be used to guide choice
      of tools for detecting change in sedentary behaviour in older adults in the
      contexts of population surveillance, intervention evaluation and individual care.

PMID- 29649235
TI  - Patient-specific musculoskeletal modeling of the hip joint for preoperative
      planning of total hip arthroplasty: A validation study based on in vivo
      measurements.
AB  - Validation of musculoskeletal models for application in preoperative planning is
      still a challenging task. Ideally, the simulation results of a patient-specific
      musculoskeletal model are compared to corresponding in vivo measurements.
      Currently, the only possibility to measure in vivo joint forces is to implant an
      instrumented prosthesis in patients undergoing a total joint replacement. In this
      study, a musculoskeletal model of the AnyBody Modeling System was adapted patient
      specifically and validated against the in vivo hip joint force measurements of
      ten subjects performing one-leg stance and level walking. The impact of four
      model parameters was evaluated; hip joint width, muscle strength, muscle
      recruitment, and type of muscle model. The smallest difference between simulated
      and in vivo hip joint force was achieved by using the hip joint width measured in
      computed tomography images, a muscle strength of 90 N/cm2, a third order
      polynomial muscle recruitment, and a simple muscle model. This parameter
      combination reached mean deviations between simulation and in vivo measurement
      during the peak force phase of 12% +/- 14% in magnitude and 11 degrees  +/- 5
      degrees  in orientation for one-leg stance and 8% +/- 6% in magnitude and 10
      degrees  +/- 5 degrees  in orientation for level walking.

PMID- 29649237
TI  - Bronchoalveolar lavage (BAL) cells in idiopathic pulmonary fibrosis express a
      complex pro-inflammatory, pro-repair, angiogenic activation pattern, likely
      associated with macrophage iron accumulation.
AB  - Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease of unknown cause
      characterized by alveolar epithelial damage, patchy interstitial fibrosis and
      diffuse microvascular abnormalities. In IPF, alveolar clustering of iron-laden
      alveolar macrophages-a common sign of microhemorrhage, has been associated with
      vascular abnormalities and worsening of pulmonary hypertension. As iron-dependent
      ROS generation has been shown to induce unrestrained macrophage activation in
      disease models of vascular damage, we explored alveolar macrophage activation
      phenotype in IPF patients (n = 16) and healthy controls (CTR, n = 7) by RNA
      sequencing of bronchoalveolar lavage (BAL) cells. The frequencies of macrophages
      in BAL cells were 86+4% and 83.4+8% in IPF and CTR groups, respectively (p-value
      = 0.41). In IPF patients, BAL cells showed increased iron-dependent ROS
      generation (p-value<0.05 vs CTR). Gene expression analysis showed
      overrepresentation of Gene Ontology processes/functions and KEGG pathways
      enriched in upregulated M1-type inflammatory (p-value<0.01), M2-type anti
      inflammatory/tissue remodeling (p-value<0.0001), and MTPP-type chronic
      inflammatory/angiogenic (p-value<0.0001) chemokine and cytokine genes. The ex
      vivo finding was confirmed by the induction of iron-dependent ROS generation and
      chemokine/cytokine overexpression of Ccl4, Cxcl10 (M1), Il1rn (M2), Cxcl2, and
      Cxcl7 (MTPP) in MH-S murine immortalized alveolar macrophages exposed to ferric
      ammonium citrate in culture (p-value<0.05 vs CTR). The data show alveolar
      macrophage expression of a pro-inflammatory, tissue remodeling and angiogenic
      complex activation pattern, suggesting that iron accumulation may play a role in
      macrophage activation.

PMID- 29649238
TI  - Generation of multidrug resistant human tissues by overexpression of the ABCG2
      multidrug transporter in embryonic stem cells.
AB  - The ABCG2 multidrug transporter provides resistance against various endo- and
      xenobiotics, and protects the stem cells against toxins and stress conditions. We
      have shown earlier that a GFP-tagged version of ABCG2 is fully functional and may
      be used to follow the expression, localization and function of this transporter
      in living cells. In the present work we have overexpressed GFP-ABCG2, driven by a
      constitutive (CAG) promoter, in HUES9 human embryonic stem cells. Stem cell
      clones were generated to express the wild-type and a substrate-mutant (R482G) GFP
      ABCG2 variant, by using the Sleeping Beauty transposon system. We found that the
      stable overexpression of these transgenes did not change the pluripotency and
      growth properties of the stem cells, nor their differentiation capacity to
      hepatocytes or cardiomyocytes. ABCG2 overexpression provided increased toxin
      resistance in the stem cells, and protected the derived cardiomyocytes against
      doxorubicin toxicity. These studies document the potential of a stable ABCG2
      expression for engineering toxin-resistant human pluripotent stem cells and
      selected stem cell derived tissues.

PMID- 29649239
TI  - Using hydrodynamic focusing to predictably alter the diameter of synthetic silk
      fibers.
AB  - Spiders and silkworms provide a model of superior processing for multifunctional
      and highly versatile high-performance fibers. Mimicking the spider's complex
      control system for chemical and mechanical gradients has remained an ongoing
      obstacle for synthetic silk production. In this study, the use of hydrodynamic
      fluid focusing within a 3D printed biomimetic spinning system to recapitulate the
      biological spinneret is explored and shown to produce predictable, small diameter
      fibers. Mirroring in silico fluid flow simulations using a hydrodynamic
      microfluidic spinning technique, we have developed a model correlating spinning
      rates, solution viscosity and fiber diameter outputs that will significantly
      advance the field of synthetic silk fiber production. The use of hydrodynamic
      focusing to produce controlled output fiber diameter simulates the natural silk
      spinning process and continues to build upon a 3D printed biomimetic spinning
      platform.

PMID- 29649236
TI  - Predictive value for cardiovascular events of common carotid intima media
      thickness and its rate of change in individuals at high cardiovascular risk -
      Results from the PROG-IMT collaboration.
AB  - AIMS: Carotid intima media thickness (CIMT) predicts cardiovascular (CVD) events,
      but the predictive value of CIMT change is debated. We assessed the relation
      between CIMT change and events in individuals at high cardiovascular risk.
      METHODS AND RESULTS: From 31 cohorts with two CIMT scans (total n = 89070) on
      average 3.6 years apart and clinical follow-up, subcohorts were drawn: (A)
      individuals with at least 3 cardiovascular risk factors without previous CVD
      events, (B) individuals with carotid plaques without previous CVD events, and (C)
      individuals with previous CVD events. Cox regression models were fit to estimate
      the hazard ratio (HR) of the combined endpoint (myocardial infarction, stroke or
      vascular death) per standard deviation (SD) of CIMT change, adjusted for CVD risk
      factors. These HRs were pooled across studies. In groups A, B and C we observed
      3483, 2845 and 1165 endpoint events, respectively. Average common CIMT was 0.79mm
      (SD 0.16mm), and annual common CIMT change was 0.01mm (SD 0.07mm), both in group
      A. The pooled HR per SD of annual common CIMT change (0.02 to 0.43mm) was 0.99
      (95% confidence interval: 0.95-1.02) in group A, 0.98 (0.93-1.04) in group B, and
      0.95 (0.89-1.04) in group C. The HR per SD of common CIMT (average of the first
      and the second CIMT scan, 0.09 to 0.75mm) was 1.15 (1.07-1.23) in group A, 1.13
      (1.05-1.22) in group B, and 1.12 (1.05-1.20) in group C. CONCLUSIONS: We confirm
      that common CIMT is associated with future CVD events in individuals at high
      risk. CIMT change does not relate to future event risk in high-risk individuals.

PMID- 29649240
TI  - A Bayesian approach to modelling the impact of hydrodynamic shear stress on
      biofilm deformation.
AB  - We investigate the feasibility of using a surrogate-based method to emulate the
      deformation and detachment behaviour of a biofilm in response to hydrodynamic
      shear stress. The influence of shear force, growth rate and viscoelastic
      parameters on the patterns of growth, structure and resulting shape of microbial
      biofilms was examined. We develop a statistical modelling approach to this
      problem, using combination of Bayesian Poisson regression and dynamic linear
      models for the emulation. We observe that the hydrodynamic shear force affects
      biofilm deformation in line with some literature. Sensitivity results also showed
      that the expected number of shear events, shear flow, yield coefficient for
      heterotrophic bacteria and extracellular polymeric substance (EPS) stiffness per
      unit EPS mass are the four principal mechanisms governing the bacteria detachment
      in this study. The sensitivity of the model parameters is temporally dynamic,
      emphasising the significance of conducting the sensitivity analysis across
      multiple time points. The surrogate models are shown to perform well, and
      produced ~ 480 fold increase in computational efficiency. We conclude that a
      surrogate-based approach is effective, and resulting biofilm structure is
      determined primarily by a balance between bacteria growth, viscoelastic
      parameters and applied shear stress.

PMID- 29649241
TI  - Discovery of urinary biomarkers to discriminate between exogenous and semi
      endogenous thiouracil in cattle: A parallel-like randomized design.
AB  - In the European Union, the use of thyreostats for animal fattening purposes has
      been banned and monitoring plans have been established to detect potential abuse.
      However, this is not always straightforward as thyreostats such as thiouracil may
      also have a semi-endogenous origin. Therefore, this study aimed at defining
      urinary metabolites, which may aid in defining the origin of detected thiouracil.
      Hereto, a parallel-like randomized in vivo study was conducted in which calves (n
      = 8) and cows (n = 8) were subjected to either a control treatment, rapeseed
      enriched diet to induce semi-endogenous formation, or thiouracil treatment. Urine
      samples (n = 330) were assessed through metabolic fingerprinting, employing
      liquid-chromatography and Q-ExactiveTM Orbitrap mass spectrometry. Urinary
      fingerprints comprised up to 40,000 features whereby multivariate discriminant
      analysis was able to point out significant metabolome differences between
      treatments (Q2(Y) >= 0.873). Using the validated models, a total of twelve
      metabolites (including thiouracil) were assigned marker potential. Combining
      these markers into age-dependent biomarker panels rendered a tool by which sample
      classification could be improved in comparison with thiouracil-based thresholds,
      and this during on-going thiouracil treatment (specificities >= 95.2% and
      sensitivities >= 85.7%), post-treatment (sensitivities >= 80% for >= 24 h after
      last administration), and simulated low-dose thiouracil treatment (exogenous
      thiouracil below 30 ng MUL-1). Moreover, the metabolic relevance of revealed
      markers was supported by the suggested identities, for which a structural link
      with thiouracil could be determined in most cases. The proposed biomarker panels
      may contribute to a more justified decision-making in monitoring thiouracil
      abuse.

PMID- 29649243
TI  - Recent trends in population levels and correlates of occupational and leisure
      sitting time in full-time employed Australian adults.
AB  - This study aimed to explore the trend in population levels, as well as the
      correlates, of occupational and leisure sitting time in full-time employed
      Australian adults between 2007 and 2015. We used data from the 2007/08, 2011/12
      and 2014/15 Australian Health Surveys, in which nationally representative samples
      of the Australian population were interviewed. Full-time (>=35 hours/week)
      employed respondents reported sitting time at work and during leisure on a usual
      workday. Trends over time and associations between socio-demographic and health
      related characteristics and sitting time were analysed in the combined dataset
      using multivariable logistic regression models. Over 21,000 observations were
      included in the analyses. Across the three surveys, approximately 51% of the
      respondents reported >=4 hours/workday occupational sitting time, 40% reported
      >=4 hours/workday leisure sitting time, and 55% reported >=7 hours/workday
      combined occupational and leisure sitting time. There were no clear trends over
      time. All potential correlates were associated with occupational sitting time and
      all but educational level were associated with leisure sitting time. The
      directions of the associations with gender, age and leisure-time physical
      activity were reversed for occupational sitting time and leisure sitting time.
      These findings show that the average levels of occupational and leisure sitting
      time on workdays were high but stable over the past decade. The observed
      differences in correlates of occupational and leisure sitting time demonstrate
      the need to assess and address sedentary behaviour domains separately in research
      and policy.

PMID- 29649242
TI  - Innovation in an E. coli evolution experiment is contingent on maintaining
      adaptive potential until competition subsides.
AB  - Key innovations are disruptive evolutionary events that enable a species to
      escape constraints and rapidly diversify. After 15 years of the Lenski long-term
      evolution experiment with Escherichia coli, cells in one of the twelve
      populations evolved the ability to utilize citrate, an abundant but previously
      untapped carbon source in the environment. Descendants of these cells became
      dominant in the population and subsequently diversified as a consequence of
      invading this vacant niche. Mutations responsible for the appearance of
      rudimentary citrate utilization and for refining this ability have been
      characterized. However, the complete nature of the genetic and/or ecological
      events that set the stage for this key innovation is unknown. In particular, it
      is unclear why it took so long for citrate utilization to evolve and why it still
      has evolved in only one of the twelve E. coli populations after 30 years of the
      Lenski experiment. In this study, we recapitulated the initial mutation needed to
      evolve citrate utilization in strains isolated from throughout the first 31,500
      generations of the history of this population. We found that there was already a
      slight fitness benefit for this mutation in the original ancestor of the
      evolution experiment and in other early isolates. However, evolution of citrate
      utilization was blocked at this point due to competition with other mutations
      that improved fitness in the original niche. Subsequently, an anti-potentiated
      genetic background evolved in which it was deleterious to evolve rudimentary
      citrate utilization. Only later, after further mutations accumulated that
      restored the benefit of this first-step mutation and the overall rate of
      adaptation in the population slowed, was citrate utilization likely to evolve.
      Thus, intense competition and the types of mutations that it favors can lead to
      short-sighted evolutionary trajectories that hide a stepping stone needed to
      access a key innovation from many future generations.

PMID- 29649244
TI  - The characterization of surgical smoke from various tissues and its implications
      for occupational safety.
AB  - Electrosurgery produces surgical smoke. Different tissues produce different
      quantities and types of smoke, so we studied the particle characteristics of this
      surgical smoke in order to analyze the implications for the occupational health
      of the operation room personnel. We estimated the deposition of particulate
      matter (PM) from surgical smoke on the respiratory tract of operation room
      personnel using clinically relevant tissues from Finnish landrace porcine tissues
      including skeletal muscle, liver, subcutaneous fat, renal pelvis, renal cortex,
      lung, bronchus, cerebral gray and white matter, and skin. In order to standardize
      the electrosurgical cuts and smoke concentrations, we built a customized computer
      controlled platform. The smoke particles were analyzed with an electrical low
      pressure impactor (ELPI), which measures the concentration and aerodynamic size
      distribution of particles with a diameter between 7 nm and 10 MUm. There were
      significant differences in the mass concentration and size distribution of the
      surgical smoke particles depending on the electrocauterized tissue. Of the
      various tissues tested, liver yielded the highest number of particles. In order
      to better estimate the health hazard, we propose that the tissues can be divided
      into three distinct classes according to their surgical smoke production: 1) high
      PM tissue for liver; 2) medium-PM tissues for renal cortex, renal pelvis, and
      skeletal muscle; and 3) low-PM tissues for skin, gray matter, white matter,
      bronchus, and subcutaneous fat.

PMID- 29649245
TI  - Women's preferences for alternative financial incentive schemes for
      breastfeeding: A discrete choice experiment.
AB  - BACKGROUND: Increasing breastfeeding rates have been associated with reductions
      in disease in babies and mothers as well as in related costs. 'Nourishing Start
      for Health (NoSH)', a financial incentive scheme has been proposed as a
      potentially effective way to increase both the number of mothers breastfeeding
      and duration of breastfeeding. AIMS: To establish women's relative preferences
      for different aspects of a financial incentive scheme for breastfeeding and to
      identify importance of scheme characteristics on probability on participation in
      an incentive scheme. METHODS: A discrete choice experiment (DCE) obtained
      information on alternative specifications of the NoSH scheme designed to promote
      continued breastfeeding duration until at least 6 weeks after birth. Four
      attributes framed alternative scheme designs: value of the incentive; minimum
      breastfeeding duration required to receive incentive; method of verifying
      breastfeeding; type of incentive. Three versions of the DCE questionnaire, each
      containing 8 different choice sets, provided 24 choice sets for analysis. The
      questionnaire was mailed to 2,531 women in the South Yorkshire Cohort (SYC) aged
      16-45 years in IMD quintiles 3-5. The analytic approach considered conditional
      and mixed effects logistic models to account for preference heterogeneity that
      may be associated with a variation in effects mediated by respondents'
      characteristics. RESULTS: 564 women completed the questionnaire and a response
      rate of 22% was achieved. Most of the included attributes were found to affect
      utility and therefore the probability to participate in the incentive scheme.
      Higher rewards were preferred, although the type of incentive significantly
      affected women's preferences on average. We found evidence for preference
      heterogeneity based on individual characteristics that mediated preferences for
      an incentive scheme.Conclusions Although participants' opinion in our sample was
      mixed, financial incentives for breastfeeding may be an acceptable and effective
      instrument to change behaviour. However, individual characteristics could mediate
      the effect and should therefore be considered when developing and targeting
      future interventions.

PMID- 29649246
TI  - Women's relative status and childbearing intentions: Empirical evidence from
      Iran.
AB  - Childbearing intentions are primary predictor of childbearing behaviors,
      particularly in low fertility societies. This study examined the role of relative
      status of women in childbearing intentions in Iran where fertility has been
      declining since 1986 and it has been around the replacement level during the last
      two decades. Data from the 2010 Iran's Multiple Indicator Demographic and Health
      Survey (IrMIDHS) were used to estimate the effect of relative status of women on
      intention to have more children among women with one child and those with two
      children. The results showed modest effect of relative status of women on future
      childbearing intentions at both parity one and two controlling for socioeconomic
      and demographic factors. One implication from this finding is that within low
      fertility regimes where fertility level is around or below replacement level, the
      relative status of women is no more as important determinant of childbearing
      intention as in situations of high fertility regimes. This interpretation is
      consistent with the fact that most of the studies showing strong effect from
      relative status of women on childbearing are based on data from the situations
      where fertility level has been at the pre-transitional level.

PMID- 29649247
TI  - Serum interleukin-6 and tumor necrosis factor-alpha are associated with early
      graft regeneration after living donor liver transplantation.
AB  - BACKGROUND: Liver graft regeneration is orchestrated by specific and sequential
      stimuli, including hepatocyte growth factors, cytokines, and catecholamines. We
      evaluated the association between preoperative serum cytokines and early liver
      graft regeneration in human living donor liver transplantation (LDLT). PATIENTS
      AND METHODS: We retrospectively reviewed the data of adult patients who underwent
      LDLT from January 2010 to December 2014. Serum cytokines, including interleukin
      (IL)-2, 6, 10, 12, 17, interferon (IFN)-gamma and tumor necrosis factor (TNF)
      alpha were measured in the recipients 1 day before surgery and on postoperative
      day (POD) 7. Liver graft volume was estimated using abdominal computed tomography
      images of the donors and recipients. RESULTS: In total, 226 patients were
      analyzed in this study. Median preoperative levels of serum cytokines were as
      follows: IL-2, 0.1 (0.1-1.6) pg/mL; IL-6, 7.3 (0.1-30.2) pg/mL; IL-10, 0.5 (0.1
      11.0) pg/mL; IL-12, 0.1 (0.1-0.1) pg/mL; IL-17, 2.0 (0.1-16.4) pg/mL; IFN-gamma,
      3.2 (0.1-16.0) pg/mL; and TNF-alpha, 9.8 (5.4-17.9) pg/mL. Higher preoperative
      serum levels of IL-6, IL-10, and TNF-alpha, dichotomized at the median, were
      associated with increased relative liver volumes by POD 7. Multivariate analysis
      revealed that higher levels of serum IL-6 and TNF-alpha were independently
      associated with increased graft volume during the first 1 week after LDLT, based
      on the lower levels of those cytokines. CONCLUSIONS: IL-6 and TNF-alpha were
      important mediators of the success of early graft regeneration in patients who
      underwent LDLT.

PMID- 29649248
TI  - Psychological wellbeing of children at public primary schools in Jimma town: An
      orphan and non-orphan comparative study.
AB  - INTRODUCTION: Orphans face multiple challenges including insufficient food,
      shelter, schooling, and medical care. Most research on orphans in developing
      countries concentrates on nutrition and health status. The present study aims to
      explore the psychological wellbeing of in-school orphaned and non-orphaned
      children. METHOD: A comparative cross-sectional study design was used in 370
      randomly selected children aged between 10 and 18. Two rosters (one for orphans
      and one for non-orphans) were created, and then 185 were selected from each
      roster. Trained field workers used structured questionnaires to obtain
      information from participants. An adapted Ryff Psychological Wellbeing Scale was
      used to measure psychological wellbeing. Mean scores were determined for each
      dimension and for total psychological wellbeing. The mean split was used to
      divide psychological wellbeing into "high" and "low". Data were coded, entered,
      cleaned, and analyzed using SPSS version 20. The independent sample t-test was
      used to determine statistically significant differences in psychological
      wellbeing between orphaned and non-orphaned children. P values < 0.05 were deemed
      statistically significant. RESULTS: Of 370 children, 185 (50%) were orphans.
      Among orphaned children, only 62 (33.5%) scored high on the total psychological
      wellbeing scale whereas 107 (57.8%) of their non-orphaned peers scored highly.
      The non-orphaned children had about 10.8 higher mean psychological wellbeing
      scores than their orphan counterparts (P<0.001). The mean (+/-SD) psychological
      wellbeing of the non-orphaned children was 164.0 (17.2) vs. 153.2 (17.2) in the
      orphaned group. CONCLUSION: The psychological wellbeing of orphans is
      significantly lower than their non-orphaned peers. Orphan support projects must
      consider psychosocial wellbeing in addition to material support.

PMID- 29649249
TI  - Optimizing adherence in HIV prevention product trials: Development and
      psychometric evaluation of simple tools for screening and adherence counseling.
AB  - BACKGROUND: Low adherence in recent HIV prevention clinical trials highlights the
      need to better understand, measure, and support product use within clinical
      trials. Conventional self-reported adherence instruments within HIV prevention
      trials, often relying on single-item questions, have proven ineffective. While
      objective adherence measures are desirable, none currently exist that apply to
      both active and placebo arms. Scales are composed of multiple items in the form
      of questions or statements that, when combined, measure a more complex construct
      that may not be directly observable. When psychometrically validated, such
      measures may better assess the multiple factors contributing to adherence/non
      adherence. This study aimed to develop and psychometrically evaluate tools to
      screen and monitor trial participants' adherence to HIV prevention products
      within the context of clinical trial research. METHODS AND FINDINGS: Based on an
      extensive literature review and conceptual framework, we identified and refined
      86 items assessing potential predictors of adherence and 48 items assessing
      adherence experience. A structured survey, including adherence items and other
      variables, was administered to former ASPIRE and Ring Study participants and
      similar non-trial participants (n = 709). We conducted exploratory factor
      analyses (EFA) to identify a reduced set of constructs and items that could be
      used at screening to predict potential adherence, and at follow-up to monitor and
      intervene on adherence. We examined associations with other variables to assess
      content and construct validity. The EFA of screener items resulted in a 6-factor
      solution with acceptable to very good internal reliability (alpha: .62-.84).
      Similar to our conceptual framework, factors represent trial-related commitment
      (Distrust of Research and Commitment to Research); alignment with trial
      requirements (Visit Adherence and Trial Incompatibility); Belief in Trial
      Benefits and Partner Disclosure. The EFA on monitoring items resulted in 4
      Product-specific factors that represent Vaginal Ring Doubts, Vaginal Ring
      Benefits, Ring Removal, and Side Effects with good to very good internal
      reliability (alpha = .71-.82). Evidence of content and construct validity was
      found; relationship to social desirability bias was examined. CONCLUSIONS: These
      scales are easy and inexpensive to administer, available in several languages,
      and are applicable regardless of randomization. Once validated prospectively,
      they could (1) screen for propensity to adhere, (2) target adherence
      support/counselling, and (3) complement biomarker measures in determining true
      efficacy of the experimental product.

PMID- 29649250
TI  - What drives centralisation in cancer care?
AB  - BACKGROUND: To improve quality of care, centralisation of cancer services in high
      volume centres has been stimulated. Studies linking specialisation and high
      (surgical) volumes to better outcomes already appeared in the 1990's. However,
      actual centralisation was a difficult process in many countries. In this study,
      factors influencing the centralisation of cancer services in the Netherlands were
      determined. MATERIAL AND METHODS: Centralisation patterns were studied for three
      types of cancer that are known to benefit from high surgical caseloads:
      oesophagus-, pancreas- and bladder cancer. The Netherlands Cancer Registry
      provided data on tumour and treatment characteristics from 2000-2013 for
      respectively 8037, 4747 and 6362 patients receiving surgery. By plotting
      timelines of centralisation of cancer surgery, relations with the appearance of
      (inter)national scientific evidence, actions of medical specialist societies,
      specific regulation and other important factors on the degree of centralisation
      were ascertained. RESULTS: For oesophagus and pancreas cancer, a gradual increase
      in centralisation of surgery is seen from 2005 and 2006 onwards following
      (inter)national scientific evidence. Centralisation steps for bladder cancer
      surgery can be seen in 2010 and 2013 anticipating on the publication of norms by
      the professional society. The most influential stimulus seems to have been
      regulations on minimum volumes. CONCLUSION: Scientific evidence on the
      relationship between volume and outcome lead to the start of centralisation of
      surgical cancer care in the Netherlands. Once a body of evidence has been
      established on organisational change that influences professional practice, in
      addition some form of regulation is needed to ensure widespread implementation.

PMID- 29649251
TI  - Linkage mapping of yeast cross protection connects gene expression variation to a
      higher-order organismal trait.
AB  - Gene expression variation is extensive in nature, and is hypothesized to play a
      major role in shaping phenotypic diversity. However, connecting differences in
      gene expression across individuals to higher-order organismal traits is not
      trivial. In many cases, gene expression variation may be evolutionarily neutral,
      and in other cases expression variation may only affect phenotype under specific
      conditions. To understand connections between gene expression variation and
      stress defense phenotypes, we have been leveraging extensive natural variation in
      the gene expression response to acute ethanol in laboratory and wild
      Saccharomyces cerevisiae strains. Previous work found that the genetic
      architecture underlying these expression differences included dozens of "hotspot"
      loci that affected many transcripts in trans. In the present study, we provide
      new evidence that one of these expression QTL hotspot loci affects natural
      variation in one particular stress defense phenotype-ethanol-induced cross
      protection against severe doses of H2O2. A major causative polymorphism is in the
      heme-activated transcription factor Hap1p, which we show directly impacts cross
      protection, but not the basal H2O2 resistance of unstressed cells. This provides
      further support that distinct cellular mechanisms underlie basal and acquired
      stress resistance. We also show that Hap1p-dependent cross protection relies on
      novel regulation of cytosolic catalase T (Ctt1p) during ethanol stress in a wild
      oak strain. Because ethanol accumulation precedes aerobic respiration and
      accompanying reactive oxygen species formation, wild strains with the ability to
      anticipate impending oxidative stress would likely be at an advantage. This study
      highlights how strategically chosen traits that better correlate with gene
      expression changes can improve our power to identify novel connections between
      gene expression variation and higher-order organismal phenotypes.

PMID- 29649252
TI  - Prevalence of psychotic disorders and its association with methodological issues.
      A systematic review and meta-analyses.
AB  - OBJECTIVES: The purpose of this study is to provide an updated systematic review
      to identify studies describing the prevalence of psychosis in order to explore
      methodological factors that could account for the variation in prevalence
      estimates. METHODS: Studies with original data related to the prevalence of
      psychosis (published between 1990 and 2015) were identified via searching
      electronic databases and reviewing manual citations. Prevalence estimates were
      sorted according to prevalence type (point, 12-months and lifetime). The
      independent association between key methodological variables and the mean effect
      of prevalence was examined (prevalence type, case-finding setting, method of
      confirming diagnosis, international classification of diseases, diagnosis
      category, and study quality) by meta-analytical techniques and random-effects
      meta-regression. RESULTS: Seventy-three primary studies were included, providing
      a total of 101 estimates of prevalence rates of psychosis. Across these studies,
      the pooled median point and 12-month prevalence for persons was 3.89 and 4.03 per
      1000 respectively; and the median lifetime prevalence was 7.49 per 1000. The
      result of the random-effects meta-regression analysis revealed a significant
      effect for the prevalence type, with higher rates of lifetime prevalence than 12
      month prevalence (p<0.001). Studies conducted in the general population presented
      higher prevalence rates than those carried out in populations attended in
      health/social services (p = 0.006). Compared to the diagnosis of schizophrenia
      only, prevalence rates were higher in the probable psychotic disorder (p = 0.022)
      and non-affective psychosis (p = 0.009). Finally, a higher study quality is
      associated with a lower estimated prevalence of psychotic disorders (p<0.001).
      CONCLUSIONS: This systematic review provides a comprehensive comparison of
      methodologies used in studies of the prevalence of psychosis, which can provide
      insightful information for future epidemiological studies in adopting the most
      relevant methodological approach.

PMID- 29649253
TI  - Prevalence and predictors of khat chewing among Ethiopian university students: A
      systematic review and meta-analysis.
AB  - BACKGROUND: Khat chewing has become a common practice among university students
      in developing countries like Ethiopia. It has a potential effect on physical,
      mental, social and cognitive aspects of student functioning. In Ethiopia, study
      findings regarding the prevalence of khat chewing were highly dispersed and
      inconsistent. Therefore, this systematic review and meta-analysis estimates the
      pooled prevalence of khat chewing and its predictors among Ethiopian university
      students. METHOD: A systematic review and meta-analysis was conducted to assess
      the prevalence and predictors of khat chewing among university students in
      Ethiopia. We searched literature from the databases of PubMed, Google Scholar,
      Science Direct, and the Cochrane Library. A total of 24 Ethiopian studies
      reporting the prevalence of khat chewing among university students were included.
      Data were extracted using a standardized data extraction format prepared in
      Microsoft Excel and the analysis was done using STATA 14 statistical software. To
      assess heterogeneity, the Cochrane Q test statistics and I2 test were used. Since
      the included studies exhibit high heterogeneity, a random effect meta-analysis
      model was computed to estimate the pooled prevalence of khat chewing. Moreover,
      the association between predictor variables, and khat chewing practice were
      examined. RESULTS: The meta-analysis of 24 studies revealed that the pooled
      prevalence of khat chewing among university students in Ethiopia was 23.22% (95%
      CI: 19.5, 27.0). In the subgroup analysis, the highest prevalence was observed in
      Oromia region (31.6%; 95CI: 21.2, 41.9) whereas the lowest prevalence was
      observed in Amhara region (18.1%; 95%CI: 12.4, 23.8). Being male OR: 2.76 (95% CI
      1.64, 4.63), family khat chewing practice OR: 2.91 (95% CI 1.06, 7.98), friend
      khat chewing habit OR: 4.74 (95% CI 3.48, 13.06), alcohol drinking OR: 7.06 (95%
      CI 5.65, 8.82) and cigarette smoking habit OR: 15.11 (95% CI 8.96, 25.51) were
      found to be predictors of khat chewing. CONCLUSION: The study found that the
      prevalence of khat chewing among university students was quite common, with
      slightly more than 1 in 5 students engaging in the use of this substance. Being
      male, family khat chewing practice, friend's khat chewing habit, alcohol
      drinking, and cigarette smoking were found to be predictors of khat chewing
      practice among university students.

PMID- 29649254
TI  - UXT is required for spermatogenesis in mice.
AB  - Male mammals must simultaneously produce prodigious numbers of sperm and maintain
      an adequate reserve of stem cells to ensure continuous production of gametes
      throughout life. Failures in the mechanisms responsible for balancing germ cell
      differentiation and spermatogonial stem cell (SSC) self-renewal can result in
      infertility. We discovered a novel requirement for Ubiquitous Expressed
      Transcript (UXT) in spermatogenesis by developing the first knockout mouse model
      for this gene. Constitutive deletion of Uxt is embryonic lethal, while
      conditional knockout in the male germline results in a Sertoli cell-only
      phenotype during the first wave of spermatogenesis that does not recover in the
      adult. This phenotype begins to manifest between 6 and 7 days post-partum, just
      before meiotic entry. Gene expression analysis revealed that Uxt deletion
      downregulates the transcription of genes governing SSC self-renewal,
      differentiation, and meiosis, consistent with its previously defined role as a
      transcriptional co-factor. Our study has revealed the first in vivo function for
      UXT in the mammalian germline as a regulator of distinct transcriptional programs
      in SSCs and differentiating spermatogonia.

PMID- 29649255
TI  - TERRA and the histone methyltransferase Dot1 cooperate to regulate senescence in
      budding yeast.
AB  - The events underlying senescence induced by critical telomere shortening are not
      fully understood. Here we provide evidence that TERRA, a non-coding RNA
      transcribed from subtelomeres, contributes to senescence in yeast lacking
      telomerase (tlc1Delta). Levels of TERRA expressed from multiple telomere ends
      appear elevated at senescence, and expression of an artificial RNA complementary
      to TERRA (anti-TERRA) binds TERRA in vivo and delays senescence. Anti-TERRA acts
      independently from several other mechanisms known to delay senescence, including
      those elicited by deletions of EXO1, TEL1, SAS2, and genes encoding RNase H
      enzymes. Further, it acts independently of the senescence delay provided by RAD52
      dependent recombination. However, anti-TERRA delays senescence in a fashion
      epistatic to inactivation of the conserved histone methyltransferase Dot1. Dot1
      associates with TERRA, and anti-TERRA disrupts this interaction in vitro and in
      vivo. Surprisingly, the anti-TERRA delay is independent of the C-terminal
      methyltransferase domain of Dot1 and instead requires only its N-terminus, which
      was previously found to facilitate release of telomeres from the nuclear
      periphery. Together, these data suggest that TERRA and Dot1 cooperate to drive
      senescence.

PMID- 29649256
TI  - Gene target selection for loop-mediated isothermal amplification for rapid
      discrimination of Treponema pallidum subspecies.
AB  - We show proof of concept for gene targets (polA, tprL, and TP_0619) that can be
      used in loop-mediated isothermal amplification (LAMP) assays to rapidly
      differentiate infection with any of the three Treponema pallidum subspecies
      (pallidum (TPA), pertenue (TPE), and endemicum (TEN)) and which are known to
      infect humans and nonhuman primates (NHPs). Four TPA, six human, and two NHP TPE
      strains, as well as two human TEN strains were used to establish and validate the
      LAMP assays. All three LAMP assays were highly specific for the target DNA.
      Amplification was rapid (5-15 min) and within a range of 10E+6 to 10E+2 of target
      DNA molecules. Performance in NHP clinical samples was similar to the one seen in
      human TPE strains. The newly designed LAMP assays provide proof of concept for a
      diagnostic tool that enhances yaws clinical diagnosis. It is highly specific for
      the target DNA and does not require expensive laboratory equipment. Test results
      can potentially be interpreted with the naked eye, which makes it suitable for
      the use in remote clinical settings.

PMID- 29649257
TI  - An experimental Staphylococcus aureus carriage and decolonization model in rhesus
      macaques (Macaca mulatta).
AB  - Our human model of nasal colonization and eradication of S. aureus is limited by
      safety issues. As rhesus macaques are closely related to humans and natural hosts
      for S. aureus, we developed an experimental decolonization and inoculation
      protocol in these animals. Animals were screened for nasal carriage of S. aureus
      and 20 carriers were selected. Decolonization was attempted using nasal mupirocin
      (10 animals) or mupirocin plus trimethoprim/sulfadiazine intramuscularly (10
      animals) both once daily for 5 days, and checked by follow-up cultures for 10
      weeks. Intranasal inoculation was performed with S. aureus strain 8325-4 in
      culture-negative animals. 11/20 animals, of which 5 received mupirocin and 6 the
      combination treatment, became culture-negative for S. aureus for 10 weeks and
      these 11 animals were subsequently inoculated. Swabs were taken once a week for 5
      weeks to test for the presence of the inoculated strain. In 3 animals, strain
      8325-4 was cultured from the nose 1 week after inoculation, indicating short-term
      survival of this strain only, a finding similar to that previously found in our
      human model. These data demonstrate that rhesus macaques may constitute a
      relevant animal model to perform S. aureus eradication and inoculation studies
      with relatively limited invasive handling of the animals.

PMID- 29649258
TI  - Clinician ratings of the Comprehensive Assessment of Psychopathic Personality
      (CAPP) in a representative sample of Spanish prison inmates: New validity
      evidence.
AB  - The Comprehensive Assessment of Psychopathic Personality (CAPP) is a concept map
      of psychopathic personality disorder (PPD). The CAPP- Institutional Rating Scale
      (IRS) is a tool designed to assess CAPP symptoms in institutional settings. The
      CAPP contains 33 personality traits organized in six domains: attachment,
      behavioural, cognitive, dominance, emotional and self. Until now, much of the
      CAPP research has been conducted out of clinical, forensic and correctional
      settings using self-ratings. In the current study, the psychometric properties
      and construct validity of the CAPP-IRS were evaluated in a non-convenience sample
      of 204 Spanish convicts. Clinician ratings were employed. Participants had been
      imprisoned for at least 6 months at Pereiro de Aguiar Penitentiary. This group of
      inmates was heterogeneous with respect to type of official charges, and
      representative as all convicts interned for at least 6 months in this prison were
      screened for participation. Classical test theory indexes of reliability,
      correlations between CAPP items and domains and external correlations and
      structural analyses demonstrated that CAPP assessment is a solid and robust way
      of evaluating psychopathy in a correctional setting. Best fit was found for a
      three-factor model: attachment and emotional items associated with a callous and
      unemotional trait, dominance and self items associated with a pathological
      interpersonal style, and behavioural and residual items from other domains
      associated with impulsivity.

PMID- 29649259
TI  - Development of the multi-epitope chimeric antigen rqTSA-25 from Taenia saginata
      for serological diagnosis of bovine cysticercosis.
AB  - Bovine cysticercosis is a worldwide distributed zoonosis caused by the larval
      form of Taenia saginata present in bovine muscles. The diagnosis is based on the
      postmortem inspection at slaughterhouses and consists of the macroscopic
      visualization of lesions caused by cysticercosis in muscle sites. However,
      parasitized animals can pass unnoticed during sanitary inspection. Thus, the
      objective of this study was to characterize and evaluate the performance of
      different peptides from different regions of T. saginata for the cysticercosis
      diagnosis using enzyme-linked immunosorbent assay. We generated and evaluated a
      new recombinant protein chimera derived from the fusion of different peptides. We
      selected three distinct regions of T. saginata and predicted six peptides with
      antigenic potential (EP2-EP7). These peptides were analyzed individually and
      selected for generating a new chimeric recombinant protein. The new protein was
      termed rqTSA-25, and its performance rates were: 93.3% sensitivity (confidence
      interval (CI) = 76-98%), 95.3% specificity (CI = 82-99%), 93% positive predictive
      value (CI = 76-98%), 95% negative predictive value (CI = 82-99%), and 95%
      accuracy. In the immunoblot, this protein showed no false positive or false
      negative reaction. Thus, the use of rqTSA-25 is recommended for the diagnosis of
      bovine cysticercosis.

PMID- 29649260
TI  - Decision support for evidence-based integration of disease control: A proof of
      concept for malaria and schistosomiasis.
AB  - AUTHOR SUMMARY: Designing and implementing effective programs for infectious
      disease control requires complex decision-making, informed by an understanding of
      the diseases, the types of disease interventions and control measures available,
      and the disease-relevant characteristics of the local community. Though disease
      modeling frameworks have been developed to address these questions and support
      decision-making, the complexity of current models presents a significant barrier
      to on-the-ground end users. The picture is further complicated when considering
      approaches for integration of different disease control programs, where co
      infection dynamics, treatment interactions, and other variables must also be
      taken into account. Here, we describe the development of an application available
      on the internet with a simple user interface, to support on-the-ground decision
      making for integrating disease control, given local conditions and practical
      constraints. The model upon which the tool is built provides predictive analysis
      for the effectiveness of integration of schistosomiasis and malaria control, two
      diseases with extensive geographical and epidemiological overlap. This proof-of
      concept method and tool demonstrate significant progress in effectively
      translating the best available scientific models to support pragmatic decision
      making on the ground, with the potential to significantly increase the impact and
      cost-effectiveness of disease control.

PMID- 29649261
TI  - Delineation and mapping of coastal shark habitat within a shallow lagoonal
      estuary.
AB  - Estuaries function as important nursery and foraging habitats for many coastal
      species, including highly migratory sharks. Pamlico Sound, North Carolina, is one
      of the largest estuaries in the continental United States and provides a variety
      of potential habitats for sharks. In order to identify and spatially delineate
      shark habitats within Pamlico Sound, shark catch and environmental data were
      analyzed from the 2007-2014 North Carolina Division of Marine Fisheries (NCDMF)
      gillnet and longline surveys conducted within the estuary. Principal species were
      identified and environmental data recorded at survey sites (depth, temperature,
      salinity, dissolved oxygen, submerged aquatic vegetation (SAV) distance, and
      inlet distance) were interpolated across Pamlico Sound to create seasonal
      environmental grids with a 90-m2 cell size. Boosted Regression Tree (BRT)
      analysis was used to identify the most important environmental factors and ranges
      associated with presence of each principal species, and the resulting models were
      used to predict shark capture probability based on the environmental values
      within the grid cells. The Atlantic Sharpnose Shark (Rhizoprionodon terraenovae),
      Blacktip Shark (Carcharhinus limbatus), Bull Shark (Carcharhinus leucas), Sandbar
      Shark (Carcharhinus plumbeus), Smooth Dogfish (Mustelus canis), and Spiny Dogfish
      (Squalus acanthias) were the principal species in Pamlico Sound. Most species
      were associated with proximity to the inlet and/or high salinity, and warm
      temperatures, but the Bull Shark preferred greater inlet distances and the Spiny
      Dogfish preferred lower temperatures than the other species. Extensive Smooth
      Dogfish habitat overlap with seagrass beds suggests that seagrass may be a
      critical part of nursery habitat for this species. Spatial delineation of shark
      habitat within the estuary will allow for better protection of essential habitat
      and assessment of potential interactions with other species.

PMID- 29649262
TI  - Antinociceptive antibiotics-loaded into solid lipid nanoparticles of prolonged
      release: Measuring pharmacological efficiency and time span on chronic
      monoarthritis rats.
AB  - Pain is a sensory experience of a complex physiological nature in which is not
      only involved the nervous system. Among its many features is the development of
      chronic pain that is more complicated to treat because of the central
      somatization processes involved, becoming inefficient treatments used in other
      forms of pain. Among them is the role of glial cells, whose participation is such
      that some authors have proposed to chronic pain as a gliopathy. Because of this,
      the drug target of possible treatments focuses on modulating nociceptive response
      affecting transduction into the central nervous system through affecting synapses
      in the dorsal horn of the spinal cord. Solid lipid nanoparticles enter the
      central nervous system, protecting the drug, and in addition to the advantage of
      having greater absorption surface, all factors that improve drug activity. This
      work is based on the development and characterization of lipid nanoparticles of
      solid phase incorporating two antibiotics, minocycline, and ciprofloxacin with
      antinociceptive properties and challenged them with a rat monoarthritis model
      using Sprague-Dawley adult male rats. The solid lipid nanoparticles were prepared
      to modify the lipid, and surfactant amounts to obtain the best encapsulation
      capacity of the antibiotics, size and z potential. By using the Randall-Selitto
      test, we measured its pharmacological efficiency as an anti-inflammatory and
      measuring the time span the antibiotics are active. The encapsulated antibiotics
      were at least 50% more efficient than the antibiotic alone, and that is possible
      to measure anti-inflammatory activity up to seven days after the antibiotic
      application. The former is important for example, in the veterinary field, since
      a single application of the antibiotic will be necessary for the complete
      treatment, avoiding excessive stress for the animals. We can conclude that
      antinociceptive antibiotics encapsulation is a very effective, environmentally
      safe and inexpensive method for improving the pharmacological efficiency and time
      span the antibiotics are acting. Since these antibiotics are both anti-microbial
      and antinociceptive, his use in the field of veterinary presents the advantage of
      being adequate in single doses, with the saving of time and stress to the animals
      under treatment.

PMID- 29649263
TI  - Validation of CZECANCA (CZEch CAncer paNel for Clinical Application) for targeted
      NGS-based analysis of hereditary cancer syndromes.
AB  - BACKGROUND: Carriers of mutations in hereditary cancer predisposition genes
      represent a small but clinically important subgroup of oncology patients. The
      identification of causal germline mutations determines follow-up management,
      treatment options and genetic counselling in patients' families. Targeted next
      generation sequencing-based analyses using cancer-specific panels in high-risk
      individuals have been rapidly adopted by diagnostic laboratories. While the use
      of diagnosis-specific panels is straightforward in typical cases, individuals
      with unusual phenotypes from families with overlapping criteria require multiple
      panel testing. Moreover, narrow gene panels are limited by our currently
      incomplete knowledge about possible genetic dispositions. METHODS: We have
      designed a multi-gene panel called CZECANCA (CZEch CAncer paNel for Clinical
      Application) for a sequencing analysis of 219 cancer-susceptibility and candidate
      predisposition genes associated with frequent hereditary cancers. RESULTS: The
      bioanalytical and bioinformatics pipeline was validated on a set of internal and
      commercially available DNA controls showing high coverage uniformity,
      sensitivity, specificity and accuracy. The panel demonstrates a reliable
      detection of both single nucleotide and copy number variants. Inter-laboratory,
      intra- and inter-run replicates confirmed the robustness of our approach.
      CONCLUSION: The objective of CZECANCA is a nationwide consolidation of cancer
      predisposition genetic testing across various clinical indications with savings
      in costs, human labor and turnaround time. Moreover, the unified diagnostics will
      enable the integration and analysis of genotypes with associated phenotypes in a
      national database improving the clinical interpretation of variants.

PMID- 29649264
TI  - Age at antiretroviral therapy initiation and cell-associated HIV-1 DNA levels in
      HIV-1-infected children.
AB  - BACKGROUND: The latent viral reservoir is the major obstacle to achieving HIV
      remission and necessitates life-long antiretroviral therapy (ART) for HIV
      infected individuals. Studies in adults and children have found that initiating
      ART soon after infection is associated with a reduction in the size of the HIV-1
      reservoir. Here we quantified cell-associated HIV-1 DNA in early-treated but
      currently older HIV-infected children suppressed on ART. METHODS: The study
      participants comprised of a cohort of 146 early-treated children with HIV-1 RNA
      <50 copies/ml enrolled as part of a clinical trial in Johannesburg, South Africa.
      A stored buffy coat sample collected after a median 4.3 years on ART and where
      HIV-1 RNA was <50 copies/ml was tested for cell-associated HIV-1 DNA levels. An
      in-house, semi-nested real-time quantitative hydrolysis probe PCR assay to detect
      total HIV-1 subtype C proviral DNA was used. Children were followed prospectively
      for up to 3 years after this measurement to investigate subsequent HIV-1 RNA
      rebound/failure while remaining on ART. Age at ART initiation, HIV-1 RNA decline
      prior to HIV-1 DNA measurement and other factors were investigated. RESULTS: A
      gradient between age at ART initiation and later HIV-1 DNA levels was observed.
      When ART was started <2 months of age, the lowest levels of cell-associated HIV-1
      DNA (median 1.4 log10copies/106 cells, interquartile range [IQR] 0.95-1.55) were
      observed compared to ART started at 2-4 months (median 1.68, IQR 1.26-1.97) or 5
      14 months of age (median1.98, IQR 1.69-2.25). A low CD4 T-cell count pre
      treatment predicted higher levels of HIV-1 DNA on later testing. The probability
      of HIV-1 RNA rebound >50 copies/ml whilst on ART within 3 years after the DNA
      measurement was 2.07 (95% CI: 1.352-3.167) times greater if the HIV-1 DNA level
      was above the median of 55 copies/106 cells. CONCLUSIONS: Cell-associated HIV-1
      DNA levels measured after more than 4 years on ART were lower the younger the age
      of the child when ART was initiated. This marker of the size of the viral
      reservoir also predicted subsequent viral rebound/treatment failure while ART was
      sustained. The results provide additional evidence of the benefits of prompt
      diagnosis and early ART initiation in newborns and infants.

PMID- 29649265
TI  - Bacterial and protozoal pathogens found in ticks collected from humans in Corum
      province of Turkey.
AB  - BACKGROUND: Tick-borne diseases are increasing all over the word, including
      Turkey. The aim of this study was to determine the bacterial and protozoan vector
      borne pathogens in ticks infesting humans in the Corum province of Turkey.
      METHODOLOGY/PRINCIPAL FINDINGS: From March to November 2014 a total of 322 ticks
      were collected from patients who attended the local hospitals with tick bites.
      Ticks were screened by real time-PCR and PCR, and obtained amplicons were
      sequenced. The dedected tick was belonging to the genus Hyalomma, Haemaphysalis,
      Rhipicephalus, Dermacentor and Ixodes. A total of 17 microorganism species were
      identified in ticks. The most prevalent Rickettsia spp. were: R. aeschlimannii
      (19.5%), R. slovaca (4.5%), R. raoultii (2.2%), R. hoogstraalii (1.9%), R.
      sibirica subsp. mongolitimonae (1.2%), R. monacensis (0.31%), and Rickettsia spp.
      (1.2%). In addition, the following pathogens were identified: Borrelia afzelii
      (0.31%), Anaplasma spp. (0.31%), Ehrlichia spp. (0.93%), Babesia microti (0.93%),
      Babesia ovis (0.31%), Babesia occultans (3.4%), Theileria spp. (1.6%), Hepatozoon
      felis (0.31%), Hepatozoon canis (0.31%), and Hemolivia mauritanica (2.1%). All
      samples were negative for Francisella tularensis, Coxiella burnetii, Bartonella
      spp., Toxoplasma gondii and Leishmania spp. CONCLUSIONS/SIGNIFICANCE: Ticks in
      Corum carry a large variety of human and zoonotic pathogens that were detected
      not only in known vectors, but showed a wider vector diversity. There is an
      increase in the prevalence of ticks infected with the spotted fever group and
      lymphangitis-associated rickettsiosis, while Ehrlichia spp. and Anaplasma spp.
      were reported for the first time from this region. B. microti was detected for
      the first time in Hyalomma marginatum infesting humans. The detection of B.
      occultans, B. ovis, Hepatozoon spp., Theileria spp. and Hemolivia mauritanica
      indicate the importance of these ticks as vectors of pathogens of veterinary
      importance, therefore patients with a tick infestation should be followed for a
      variety of pathogens with medical importance.

PMID- 29649266
TI  - Preoperative dynamic breast magnetic resonance imaging kinetic features using
      computer-aided diagnosis: Association with survival outcome and tumor
      aggressiveness in patients with invasive breast cancer.
AB  - OBJECTIVES: To evaluate whether preoperative breast dynamic contrast-enhanced
      (DCE) magnetic resonance (MR) imaging kinetic features, assessed using computer
      aided diagnosis (CAD), can predict survival outcome and tumor aggressiveness in
      patients with invasive breast cancer. MATERIALS AND METHODS: Between March and
      December 2011, 301 women who underwent preoperative DCE MR imaging for invasive
      breast cancer, with CAD data, were identified. All MR images were retrospectively
      evaluated using a commercially available CAD system. The following kinetic
      parameters were prospectively recorded for each lesion: initial peak enhancement,
      the proportion of early phase medium and rapid enhancement, and the proportion of
      delayed phase persistent, plateau, and washout enhancement. The Cox proportional
      hazards model was used to determine the association between the kinetic features
      assessed by CAD and disease-free survival (DFS). The peak signal intensity and
      kinetic enhancement profiles were compared with the clinical-pathological
      variables. RESULTS: There were 32 recurrences during a mean follow-up time of
      55.2 months (range, 5-72 months). Multivariate analysis revealed that a higher
      peak enhancement (DFS hazard ratio, 1.004 [95% confidence interval (CI): 1.001,
      1.006]; P = .013) on DCE MR imaging and a triple-negative subtype (DFS hazard
      ratio, 21.060 [95% CI: 2.675, 165.780]; P = .004) were associated with a poorer
      DFS. Higher peak enhancement was significantly associated with a higher tumor
      stage, clinical stage, and histologic grade. CONCLUSIONS: Patients with breast
      cancer who showed higher CAD-derived peak enhancement on breast MR imaging had
      worse DFS. Peak enhancement and volumetric analysis of kinetic patterns were
      useful for predicting tumor aggressiveness.

PMID- 29649267
TI  - Anonymity-preserving Reputation Management System for health sector.
AB  - In health sector, trust is considered important because it indirectly influences
      the quality of health care through patient satisfaction, adherence and the
      continuity of its relationship with health care professionals and the promotion
      of accurate and timely diagnoses. One of the important requirements of TRSs in
      the health sector is rating secrecy, which mandates that the identification
      information about the service consumer should be kept secret to prevent any
      privacy violation. Anonymity and trust are two imperative objectives, and no
      significant explicit efforts have been made to achieve both of them at the same
      time. In this paper, we present a framework for solving the problem of
      reconciling trust with anonymity in the health sector. Our solution comprises
      Anonymous Reputation Management (ARM) protocol and Context-aware Trustworthiness
      Assessment (CTA) protocol. ARM protocol ensures that only those service consumers
      who received a service from a specific service provider provide a recommendation
      score anonymously with in the specified time limit. The CTA protocol computes the
      reputation of a user as a service provider and as a recommender. To determine the
      correctness of the proposed ARM protocol, formal modelling and verification are
      performed using High Level Petri Nets (HLPN) and Z3 Solver. Our simulation
      results verify the accuracy of the proposed context-aware trust assessment
      scheme.

PMID- 29649268
TI  - A case-control study of lower urinary-tract infections, associated antibiotics
      and the risk of developing prostate cancer using PCBaSe 3.0.
AB  - OBJECTIVES: To investigate the association between lower urinary-tract
      infections, their associated antibiotics and the subsequent risk of developing
      PCa. SUBJECTS/PATIENTS (OR MATERIALS) AND METHODS: Using data from the Swedish
      PCBaSe 3.0, we performed a matched case-control study (8762 cases and 43806
      controls). Conditional logistic regression analysis was used to assess the
      association between lower urinary-tract infections, related antibiotics and PCa,
      whilst adjusting for civil status, education, Charlson Comorbidity Index and time
      between lower urinary-tract infection and PCa diagnosis. RESULTS: It was found
      that lower urinary-tract infections did not affect PCa risk, however, having a
      lower urinary-tract infection or a first antibiotic prescription 6-12 months
      before PCa were both associated with an increased risk of PCa (OR: 1.50, 95% CI:
      1.23-1.82 and 1.96, 1.71-2.25, respectively), as compared to men without lower
      urinary-tract infections. Compared to men with no prescriptions for antibiotics,
      men who were prescribed >=10 antibiotics, were 15% less likely to develop PCa
      (OR: 0.85, 95% CI: 0.78-0.91). CONCLUSION: PCa was not found to be associated
      with diagnosis of a urinary-tract infection or frequency, but was positively
      associated with short time since diagnoses of lower urinary-tract infection or
      receiving prescriptions for antibiotics. These observations can likely be
      explained by detection bias, which highlights the importance of data on the
      diagnostic work-up when studying potential risk factors for PCa.

PMID- 29649269
TI  - Carriage of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella
      catarrhalis, and Staphylococcus aureus in Indonesian children: A cross-sectional
      study.
AB  - Streptococcus pneumoniae is an important cause of infection and commonly
      colonizes the nasopharynx of young children, along with other potentially
      pathogenic bacteria. The objectives of this study were to estimate the carriage
      prevalence of S. pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and
      Staphylococcus aureus in young children in Indonesia, and to examine interactions
      between these bacterial species. 302 healthy children aged 12-24 months were
      enrolled in community health centers in the Bandung, Central Lombok, and Padang
      regions. Nasopharyngeal swabs were collected and stored according to World Health
      Organization recommendations, and bacterial species detected by qPCR.
      Pneumococcal serotyping was conducted by microarray and latex
      agglutination/Quellung. Overall carriage prevalence was 49.5% for S. pneumoniae,
      27.5% for H. influenzae, 42.7% for M. catarrhalis, and 7.3% for S. aureus.
      Prevalence of M. catarrhalis and S. pneumoniae, as well as pneumococcal serotype
      distribution, varied by region. Positive associations were observed for S.
      pneumoniae and M. catarrhalis (OR 3.07 [95%CI 1.91-4.94]), and H. influenzae and
      M. catarrhalis (OR 2.34 [95%CI 1.40-3.91]), and a negative association was found
      between M. catarrhalis and S. aureus (OR 0.06 [95%CI 0.01-0.43]). Densities of S.
      pneumoniae, H. influenzae, and M. catarrhalis were positively correlated when two
      of these species were present. Prior to pneumococcal vaccine introduction,
      pneumococcal carriage prevalence and serotype distribution varies among children
      living in different regions of Indonesia. Positive associations in both carriage
      and density identified among S. pneumoniae, H. influenzae, and M. catarrhalis
      suggest a synergistic relationship among these species with potential clinical
      implications.

PMID- 29649270
TI  - The quality of reporting in randomized controlled trials of acupuncture for knee
      osteoarthritis: A cross-sectional survey.
AB  - OBJECTIVE: To assess the reporting quality of acupuncture trials for knee
      osteoarthritis (KOA), and explore the factors associated with the reporting.
      METHOD: Three English and four Chinese databases were searched from inception to
      December 2016 for randomized control trials testing effects of acupuncture for
      knee osteoarthritis. We used the standard CONSORT (2010 version), CONSORT
      Extension for Non-Pharmacological Treatments, and STRICTA for measuring the
      quality of reporting. Using pre-specified study characteristics, we undertook
      regression analyses to examine factors associated with the reporting quality.
      RESULTS: A total of 318 RCT reports were included. For the standard CONSORT, ten
      items were substantially under-reported (reported in less than 5% of RCTs),
      including specification of important changes to methods after trial commencement
      (0.6%), description of any changes to trial outcomes (0.0%), implementation of
      interim analyses and stopping guidelines (0.6%), statement about why the trial
      ended or was stopped (1.6%), statement about the registration status (4.4%),
      accessibility of full trial protocol (4.7%), implementation of randomization
      (4.7%), description of the similarity of interventions (3.5%), conduct of
      ancillary analyses (3.8%) and presentation of methods for additional analyses
      (4.4%). Four of the STRICTA items were under-reported (reported in less than 10%
      of RCTs), including description of acupuncture style (8.5%), presentation of
      extent to which treatment varied (1.3%), statement of practitioner background
      (7.2%) and rationale for the control (9.1%). For CONSORT Extension, the reporting
      was poor across all items (reported in less than 10% of trials). Trials including
      authors with expertise in epidemiology or statistics, published in English, or
      enrolling patients from multiple centers were more likely to have better
      reporting. CONCLUSIONS: The reporting in RCTs of acupuncture for KOA was
      generally poor. To improve the reporting quality, journals should encourage
      strict adherence to the reporting guidelines.

PMID- 29649271
TI  - Automated analysis of cell migration and nuclear envelope rupture in confined
      environments.
AB  - Recent in vitro and in vivo studies have highlighted the importance of the cell
      nucleus in governing migration through confined environments. Microfluidic
      devices that mimic the narrow interstitial spaces of tissues have emerged as
      important tools to study cellular dynamics during confined migration, including
      the consequences of nuclear deformation and nuclear envelope rupture. However,
      while image acquisition can be automated on motorized microscopes, the analysis
      of the corresponding time-lapse sequences for nuclear transit through the pores
      and events such as nuclear envelope rupture currently requires manual analysis.
      In addition to being highly time-consuming, such manual analysis is susceptible
      to person-to-person variability. Studies that compare large numbers of cell types
      and conditions therefore require automated image analysis to achieve sufficiently
      high throughput. Here, we present an automated image analysis program to register
      microfluidic constrictions and perform image segmentation to detect individual
      cell nuclei. The MATLAB program tracks nuclear migration over time and records
      constriction-transit events, transit times, transit success rates, and nuclear
      envelope rupture. Such automation reduces the time required to analyze migration
      experiments from weeks to hours, and removes the variability that arises from
      different human analysts. Comparison with manual analysis confirmed that both
      constriction transit and nuclear envelope rupture were detected correctly and
      reliably, and the automated analysis results closely matched a manual analysis
      gold standard. Applying the program to specific biological examples, we
      demonstrate its ability to detect differences in nuclear transit time between
      cells with different levels of the nuclear envelope proteins lamin A/C, which
      govern nuclear deformability, and to detect an increase in nuclear envelope
      rupture duration in cells in which CHMP7, a protein involved in nuclear envelope
      repair, had been depleted. The program thus presents a versatile tool for the
      study of confined migration and its effect on the cell nucleus.

PMID- 29649272
TI  - In-field and in-vitro study of the moss Leptodictyum riparium as bioindicator of
      toxic metal pollution in the aquatic environment: Ultrastructural damage,
      oxidative stress and HSP70 induction.
AB  - This study evaluates the effects of toxic metal pollution in the highly
      contaminated Sarno River (South Italy), by using the aquatic moss Leptodictyum
      riparium in bags at 3 representative sites of the river. Biological effects were
      assessed by metal bioaccumulation, ultrastructural changes, oxidative stress, as
      Reactive Oxygen Species (ROS) production and Glutathione S-transferase (GST)
      activity, as well as Heat Shock Proteins 70 (HSP70s) induction. The results
      showed that L. riparium is a valuable bioindicator for toxic metal pollution of
      water ecosystem, accumulating different amounts of toxic metals from the aquatic
      environment. Toxic metal pollution caused severe ultrastructural damage, as well
      as increased ROS production and induction of GST and HSP70s, in the samples
      exposed at the polluted sites. To assess the role and the effect of toxic metals
      on L. riparium, were also cultured in vitro with Cd, Cr, Cu, Fe, Ni, Pb, Zn at
      the same concentrations as measured at the 3 sites. Ultrastructure, ROS, GST, and
      HSP70s resulted severely affected by toxic metals. Based on our findings, we
      confirm L. riparium as a model organism in freshwater biomonitoring surveys, and
      GST and HSP70s as promising biomarkers of metal toxicity.

PMID- 29649273
TI  - Do all infants need vitamin D supplementation?
AB  - A high prevalence of vitamin D deficiency (VDD) in children has been observed
      worldwide, but there are few studies on the nutritional status of vitamin D (VD)
      in healthy infants. The main cause of deficiency in healthy children is
      breastfeeding without supplementation and lack or insufficiency of sun exposure.
      The aims of this study were to determine serum concentrations of 25(OH)D and
      verify its association with parathyroid hormone (PTH) concentrations and use of
      VD supplementation in healthy infants aged >= 6 to <= 24 months attended at two
      Primary Health Care Units in Ribeirao Preto city, Sao Paulo, Brazil. A cross
      sectional, observational and analytical study was performed in which serum
      concentrations of 25(OH)D, PTH, alkaline phosphatase (AP), calcium (Ca),
      phosphorus (P) and albumin were determined in 155 healthy infants. Information on
      sun exposure, sociodemographic aspects of mothers and clinical and nutritional
      characteristics of infants were obtained through interviews with responsible
      infants's legal representatives. Ten infants (6%) presented deficient 25(OH)D
      serum concentration (<=20ng/ml) and 46 (30%), insufficient (21 to 29ng/ml). No
      changes in serum P, Ca and albumin concentrations were detected. Only one infant
      had an increase in PTH serum concentrations. 35% (55/155) of infants had high AP
      e 40% (22/55) presented insufficient serum concentrations of 25(OH)D but none
      presented deficient ones. There was a weak association between serum
      concentrations of 25(OH)D and PTH and an association between serum concentrations
      of 25(OH)D and P when adjusted for sex, age and BMI. There were no associations
      between inadequate serum concentrations of 25(OH)D (deficient ou insufficient),
      sun exposure and VD supplementation. This study found a low prevalence of
      deficient 25(OH)D serum concentration and high prevalence of insufficient ones
      which was not associated with changes in serum PTH, AP, P, Ca and albumin
      concentrations, VD supplementation and the formula volume intake.

PMID- 29649274
TI  - Present-day monitoring underestimates the risk of exposure to pathogenic bacteria
      from cold water storage tanks.
AB  - Water-borne bacteria, found in cold water storage tanks, are causative agents for
      various human infections and diseases including Legionnaires' disease.
      Consequently, regular microbiological monitoring of tank water is undertaken as
      part of the regulatory framework used to control pathogenic bacteria. A key
      assumption is that a small volume of water taken from under the ball valve (where
      there is easy access to the stored water) will be representative of the entire
      tank. To test the reliability of this measure, domestic water samples taken from
      different locations of selected tanks in London properties between November 2015
      and July 2016 were analysed for TVCs, Pseudomonas and Legionella at an accredited
      laboratory, according to regulatory requirements. Out of ~6000 tanks surveyed,
      only 15 were selected based on the ability to take a water sample from the normal
      sampling hatch (located above the ball valve) and from the far end of the tank
      (usually requiring disassembly of the tank lid with risk of structural damage),
      and permission being granted by the site manager to undertake the additional
      investigation and sampling. Despite seasonal differences in water temperature, we
      found 100% compliance at the ball valve end. In contrast, 40% of the tanks
      exceeded the regulatory threshold for temperature at the far end of the tank in
      the summer months. Consequently, 20% of the tanks surveyed failed to trigger
      appropriate regulatory action based on microbiological analyses of the water
      sample taken under the ball valve compared to the far end sample using present
      day standards. These data show that typical water samples collected for routine
      monitoring may often underestimate the microbiological status of the water
      entering the building, thereby increasing the risk of exposure to water bourne
      pathogens with potential public health implications. We propose that water
      storage tanks should be redesigned to allow access to the far end of tanks for
      routine monitoring purposes, and that water samples used to ascertain the
      regulatory compliance of stored water in tanks should be taken at the point at
      which water is abstracted for use in the building.

PMID- 29649275
TI  - Evaluation of the relationship between plasma lipids and abdominal aortic
      aneurysm: A Mendelian randomization study.
AB  - Studies have reported that higher circulating levels of total cholesterol (TC),
      low-density lipoprotein (LDL) cholesterol and lower of high-density lipoprotein
      (HDL) cholesterol may be associated with increased risk of abdominal aortic
      aneurysm (AAA). Whether dyslipidemia causes AAA is still unclear and is
      potentially testable using a Mendelian randomization (MR) approach. We
      investigated the associations between blood lipids and AAA using two-sample MR
      analysis with SNP-lipids association estimates from a published genome-wide
      association study of blood lipids (n = 188,577) and SNP-AAA association estimates
      from European Americans (EAs) of the Atherosclerosis Risk in Communities (ARIC)
      study (n = 8,793). We used inverse variance weighted (IVW) MR as the primary
      method and MR-Egger regression and weighted median MR estimation as sensitivity
      analyses. Over a median of 22.7 years of follow-up, 338 of 8,793 ARIC
      participants experienced incident clinical AAA. Using the IVW method, we observed
      positive associations of plasma LDL cholesterol and TC with the risk of AAA (odds
      ratio (OR) = 1.55, P = 0.02 for LDL cholesterol and OR = 1.61, P = 0.01 for TC
      per 1 standard deviation of lipid increment). Using the MR-Egger regression and
      weighted median methods, we were able to validate the association of AAA risk
      with TC, although the associations were less consistent for LDL cholesterol due
      to wider confidence intervals. Triglycerides and HDL cholesterol were not
      associated with AAA in any of the MR methods. Assuming instrumental variable
      assumptions are satisfied, our finding suggests that higher plasma TC and LDL
      cholesterol are causally associated with the increased risk of AAA in EAs.

PMID- 29649276
TI  - Carbapenem-resistant Gram-negative pathogens in a German university medical
      center: Prevalence, clinical implications and the role of novel beta-lactam/beta
      lactamase inhibitor combinations.
AB  - OBJECTIVES: To determine the spectrum of infections with multidrug-resistant Gram
      negative bacteria (MDR-GNB) and the clinical impact of the newly available
      betalactam/betalactamase inhibitor combinations ceftolozane/tazobactam and
      ceftazidime/avibactam in a German academic tertiary care center. METHODS:
      Retrospective analysis. RESULTS: Between September 1, 2015 and August 31, 2016,
      119 individual patients (0.22% of all hospital admissions) were colonized or
      infected with carbapenem-resistant MDR-GNB. The species distribution was
      Pseudomonas aeruginosa, n = 66; Enterobacteriaceae spp., n = 44; and
      Acinetobacter baumannii, n = 18. In 9 patients, carbapenem-resistant isolates
      belonging to more than one species were detected. Infection was diagnosed in 50
      patients (total: 42.0%; nosocomial pneumonia: n = 23, 19.3%; bloodstream
      infection: n = 11, 9.2%). Antimicrobial treatment with broad-spectrum antibiotics
      prior to detection of a carbapenem-resistant isolate was documented in 105
      patients (88.2%, prior administration of carbapenems: 62.2%). Nosocomial
      transmission was documented in 29 patients (24.4%). In 26 patients (21.8%), at
      least one carbapenem-susceptible, third-generation cephalosporin non-susceptible
      isolate was documented prior to detection of a carbapenem-resistant isolate
      belonging to the same species (median 38 days, IQR 23-78). 12 patients (10.1%)
      had documented previous contact to the healthcare system in a country with high
      burden of carbapenemase-producing strains. Genes encoding carbapenemases were
      detected in 60/102 patient isolates (58.8%; VIM-2, n = 25; OXA-48, n = 21; OXA-23
      like, n = 10). Susceptibility to colistin was 94.3%. Ceftolozane/tazobactam and
      ceftazidime/avibactam were administered to 3 and 5 patients, respectively (in
      hospital mortality: 66% and 100%). Development of drug-resistance under therapy
      was observed for both antimicrobials. CONCLUSIONS: i) The major predisposing
      factors for acquisition of carbapenem-resistant MDR-GNB were selective pressure
      due to preceding antimicrobial therapy and nosocomial transmission. ii) Colistin
      remains the backbone of antimicrobial chemotherapy for infections caused by
      carbapenem-resistant MDR-GNB. iii) Novel beta-lactam/beta-lactamase inhibitor
      combinations are of limited usefulness in our setting because of the high
      prevalence of Ambler class B carbapenemases and the emergence of
      nonsusceptibility under therapy.

PMID- 29649277
TI  - Estimated prevalence of undiagnosed atrial fibrillation in the United States.
AB  - INTRODUCTION: As atrial fibrillation (AF) is often asymptomatic, it may remain
      undiagnosed until or even after development of complications, such as stroke.
      Consequently the observed prevalence of AF may underestimate total disease
      burden. METHODS: To estimate the prevalence of undiagnosed AF in the United
      States, we performed a retrospective cohort modeling study in working age (18-64)
      and elderly (>=65) people using commercial and Medicare administrative claims
      databases. We identified patients in years 2004-2010 with incident AF following
      an ischemic stroke. Using a back-calculation methodology, we estimated the
      prevalence of undiagnosed AF as the ratio of the number of post-stroke AF
      patients and the CHADS2-specific stroke probability for each patient, adjusting
      for age and gender composition based on United States census data. RESULTS: The
      estimated prevalence of AF (diagnosed and undiagnosed) was 3,873,900 (95%CI:
      3,675,200-4,702,600) elderly and 1,457,100 (95%CI: 1,218,500-1,695,800) working
      age adults, representing 10.0% and 0.92% of the respective populations. Of these,
      698,900 were undiagnosed: 535,400 (95%CI: 331,900-804,400) elderly and 163,500
      (95%CI: 17,700-400,000) working age adults, representing 1.3% and 0.09% of the
      respective populations. Among all undiagnosed cases, 77% had a CHADS2 score >=1,
      and 56% had CHADS2 score >=2. CONCLUSIONS: Using a back-calculation approach, we
      estimate that the total AF prevalence in 2009 was 5.3 million of which 0.7
      million (13.1% of AF cases) were undiagnosed. Over half of the modeled population
      with undiagnosed AF was at moderate to high risk of stroke.

PMID- 29649278
TI  - Quantitative surveillance of shiga toxins 1 and 2, Escherichia coli O178 and O157
      in feces of western-Canadian slaughter cattle enumerated by droplet digital PCR
      with a focus on seasonality and slaughterhouse location.
AB  - Often Escherichia coli are harmless and/or beneficial bacteria inhabiting the
      gastrointestinal tract of livestock and humans. However, Shiga toxin-producing E.
      coli (STEC) have been linked to human disease. Cattle are the primary reservoir
      for STEC and STEC "super-shedders" are considered to be a major contributor in
      animal to animal transmission. Among STEC, O157:H7 is the most recognized
      serotype, but in recent years, non-O157 STEC have been increasingly linked to
      human disease. In Argentina and Germany, O178 is considered an emerging pathogen.
      Our objective was to compare populations of E. coli O178, O157, shiga toxin 1 and
      2 in western Canadian cattle feces from a sampling pool of ~80,000 beef cattle
      collected at two slaughterhouses. Conventional PCR was utilized to screen 1,773
      samples for presence/absence of E. coli O178. A subset of samples (n = 168) was
      enumerated using droplet digital PCR (ddPCR) and proportions of O178, O157 and
      shiga toxins 1 & 2 specific-fragments were calculated as a proportion of generic
      E. coli (GEC) specific-fragments. Distribution of stx1 and stx2 was determined by
      comparing stx1, stx2 and O157 enumerations. Conventional PCR detected the
      presence of O178 in 873 of 1,773 samples and ddPCR found the average proportion
      of O178, O157, stx1 and stx2 in the samples 2.8%, 0.6%, 1.4% and 0.5%,
      respectively. Quantification of stx1 and stx2 revealed more virulence genes than
      could be exclusively attributed to O157. Our results confirmed the presence of E.
      coli O178 in western Canadian cattle and ddPCR revealed O178 as a greater
      proportion of GEC than was O157. Our results suggests: I) O178 may be an emerging
      subgroup in Canada and II) monitoring virulence genes may be a more relevant
      target for food-safety STEC surveillance compared to current serogroup screening.

PMID- 29649279
TI  - Spatial and temporal behavioural responses of wild cattle to tropical forest
      degradation.
AB  - Identifying the consequences of tropical forest degradation is essential to
      mitigate its effects upon forest fauna. Large forest-dwelling mammals are often
      highly sensitive to environmental perturbation through processes such as
      fragmentation, simplification of habitat structure, and abiotic changes including
      increased temperatures where the canopy is cleared. Whilst previous work has
      focused upon species richness and rarity in logged forest, few look at spatial
      and temporal behavioural responses to forest degradation. Using camera traps, we
      explored the relationships between diel activity, behavioural expression, habitat
      use and ambient temperature to understand how the wild free-ranging Bornean
      banteng (Bos javanicus lowi) respond to logging and regeneration. Three secondary
      forests in Sabah, Malaysian Borneo were studied, varying in the time since last
      logging (6-23 years). A combination of generalised linear mixed models and
      generalised linear models were constructed using >36,000 trap-nights. Temperature
      had no significant effect on activity, however it varied markedly between
      forests, with the period of intense heat shortening as forest regeneration
      increased over the years. Bantengs regulated activity, with a reduction during
      the wet season in the most degraded forest (z = -2.6, Std. Error = 0.13, p =
      0.01), and reductions during midday hours in forest with limited regeneration,
      however after >20 years of regrowth, activity was more consistent throughout the
      day. Foraging and use of open canopy areas dominated the activity budget when
      regeneration was limited. As regeneration advanced, this was replaced by greater
      investment in travelling and using a closed canopy. Forest degradation modifies
      the ambient temperature, and positively influences flooding and habitat
      availability during the wet season. Retention of a mosaic of mature forest
      patches within commercial forests could minimise these effects and also provide
      refuge, which is key to heat dissipation and the prevention of thermal stress,
      whilst retention of degraded forest could provide forage.

PMID- 29649280
TI  - Evolution of structural diversity of trichothecenes, a family of toxins produced
      by plant pathogenic and entomopathogenic fungi.
AB  - Trichothecenes are a family of terpenoid toxins produced by multiple genera of
      fungi, including plant and insect pathogens. Some trichothecenes produced by the
      fungus Fusarium are among the mycotoxins of greatest concern to food and feed
      safety because of their toxicity and frequent occurrence in cereal crops, and
      trichothecene production contributes to pathogenesis of some Fusarium species on
      plants. Collectively, fungi produce over 150 trichothecene analogs: i.e.,
      molecules that share the same core structure but differ in patterns of
      substituents attached to the core structure. Here, we carried out genomic,
      phylogenetic, gene-function, and analytical chemistry studies of strains from
      nine fungal genera to identify genetic variation responsible for trichothecene
      structural diversity and to gain insight into evolutionary processes that have
      contributed to the variation. The results indicate that structural diversity has
      resulted from gain, loss, and functional changes of trichothecene biosynthetic
      (TRI) genes. The results also indicate that the presence of some substituents has
      arisen independently in different fungi by gain of different genes with the same
      function. Variation in TRI gene duplication and number of TRI loci was also
      observed among the fungi examined, but there was no evidence that such genetic
      differences have contributed to trichothecene structural variation. We also
      inferred ancestral states of the TRI cluster and trichothecene biosynthetic
      pathway, and proposed scenarios for changes in trichothecene structures during
      divergence of TRI cluster homologs. Together, our findings provide insight into
      evolutionary processes responsible for structural diversification of toxins
      produced by pathogenic fungi.

PMID- 29649281
TI  - Classification for long-term survival in oligometastatic patients treated with
      ablative radiotherapy: A multi-institutional pooled analysis.
AB  - BACKGROUND: Radiotherapy is increasingly used to treat oligometastatic patients.
      We sought to identify prognostic criteria in oligometastatic patients undergoing
      definitive hypofractionated image-guided radiotherapy (HIGRT). METHODS:
      Exclusively extracranial oligometastatic patients treated with HIGRT were pooled.
      Characteristics including age, sex, primary tumor type, interval to metastatic
      diagnosis, number of treated metastases and organs, metastatic site, prior
      systemic therapy for primary tumor treatment, prior definitive metastasis
      directed therapy, and systemic therapy for metastasis associated with overall
      survival (OS), progression-free survival (PFS), and treated metastasis control
      (TMC) were assessed by the Cox proportional hazards method. Recursive
      partitioning analysis (RPA) identified prognostic risk strata for OS and PFS
      based on pretreatment factors. RESULTS: 361 patients were included. Primary
      tumors included non-small cell lung (17%), colorectal (19%), and breast cancer
      (16%). Three-year OS was 56%, PFS was 24%, and TMC was 72%. On multivariate
      analysis, primary tumor, interval to metastases, treated metastases number, and
      mediastinal/hilar lymph node, liver, or adrenal metastases were associated with
      OS. Primary tumor site, involved organ number, liver metastasis, and prior
      primary disease chemotherapy were associated with PFS. OS RPA identified five
      classes: class 1: all breast, kidney, or prostate cancer patients (BKP) (3-year
      OS 75%, 95% CI 66-85%); class 2: patients without BKP with disease-free interval
      of 75+ months (3-year OS 85%, 95% CI 67-100%); class 3: patients without BKP,
      shorter disease-free interval, <= two metastases, and age < 62 (3-year OS 55%,
      95% CI 48-64%); class 4: patients without BKP, shorter disease-free interval, >=
      three metastases, and age < 62 (3-year OS 38%, 95% CI 24-60%); class 5: all
      others (3-year OS 13%, 95% CI 5-35%). Higher biologically effective dose (BED) (p
      < 0.01) was associated with OS. CONCLUSIONS: We identified clinical factors
      defining oligometastatic patients with favorable outcomes, who we hypothesize are
      most likely to benefit from metastasis-directed therapy.

PMID- 29649282
TI  - Host Pah1p phosphatidate phosphatase limits viral replication by regulating
      phospholipid synthesis.
AB  - Replication of positive-strand RNA viruses [(+)RNA viruses] takes place in
      membrane-bound viral replication complexes (VRCs). Formation of VRCs requires
      virus-mediated manipulation of cellular lipid synthesis. Here, we report
      significantly enhanced brome mosaic virus (BMV) replication and much improved
      cell growth in yeast cells lacking PAH1 (pah1Delta), the sole yeast ortholog of
      human LIPIN genes. PAH1 encodes Pah1p (phosphatidic acid phosphohydrolase), which
      converts phosphatidate (PA) to diacylglycerol that is subsequently used for the
      synthesis of the storage lipid triacylglycerol. Inactivation of Pah1p leads to
      altered lipid composition, including high levels of PA, total phospholipids,
      ergosterol ester, and free fatty acids, as well as expansion of the nuclear
      membrane. In pah1Delta cells, BMV replication protein 1a and double-stranded RNA
      localized to the extended nuclear membrane, there was a significant increase in
      the number of VRCs formed, and BMV genomic replication increased by 2-fold
      compared to wild-type cells. In another yeast mutant that lacks both PAH1 and
      DGK1 (encodes diacylglycerol kinase converting diacylglycerol to PA), which has a
      normal nuclear membrane but maintains similar lipid compositional changes as in
      pah1Delta cells, BMV replicated as efficiently as in pah1Delta cells, suggesting
      that the altered lipid composition was responsible for the enhanced BMV
      replication. We further showed that increased levels of total phospholipids play
      an important role because the enhanced BMV replication required active synthesis
      of phosphatidylcholine, the major membrane phospholipid. Moreover, overexpression
      of a phosphatidylcholine synthesis gene (CHO2) promoted BMV replication.
      Conversely, overexpression of PAH1 or plant PAH1 orthologs inhibited BMV
      replication in yeast or Nicotiana benthamiana plants. Competing with its host for
      limited resources, BMV inhibited host growth, which was markedly alleviated in
      pah1Delta cells. Our work suggests that Pah1p promotes storage lipid synthesis
      and thus represses phospholipid synthesis, which in turn restricts both viral
      replication and cell growth during viral infection.

PMID- 29649283
TI  - Design and preclinical characterization of ALXN1210: A novel anti-C5 antibody
      with extended duration of action.
AB  - Eculizumab, a monoclonal antibody (mAb) directed against complement protein C5,
      is considered to be the current standard of care for patients with paroxysmal
      nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome. This study
      describes the generation and preclinical attributes of ALXN1210, a new long
      acting anti-C5 mAb, obtained through select modifications to eculizumab to both
      largely abolish target-mediated drug disposition (TMDD) and increase recycling
      efficiency via the neonatal Fc receptor (FcRn). To attenuate the effect of TMDD
      on plasma terminal half-life (t1/2), histidine substitutions were engineered into
      the complementarity-determining regions of eculizumab to enhance the dissociation
      rate of the mAb:C5 complex in the acidic early endosome relative to the slightly
      basic pH of blood. Antibody variants with optimal pH-dependent binding to C5
      exhibited little to no TMDD in mice in the presence of human C5. To further
      enhance the efficiency of FcRn-mediated recycling of the antibody, two additional
      substitutions were introduced to increase affinity for human FcRn. These
      substitutions yielded an additional doubling of the t1/2 of surrogate anti-mouse
      C5 antibodies with reduced TMDD in transgenic mice expressing the human FcRn. In
      conclusion, ALXN1210 is a promising new therapeutic candidate currently in
      clinical development for treatment of patients with PNH and atypical hemolytic
      uremic syndrome.

PMID- 29649284
TI  - Sulfasalazine, an inhibitor of the cystine-glutamate antiporter, reduces DNA
      damage repair and enhances radiosensitivity in murine B16F10 melanoma.
AB  - The sodium-independent cystine-glutamate antiporter plays an important role in
      extracellular cystine uptake. It comprises the transmembrane protein, xCT and its
      chaperone, CD98. Because glutathione is only weakly cell membrane permeable,
      cellular uptake of its precursor, cystine, is known to be a key step in
      glutathione synthesis. Moreover, it has been reported that xCT expression affects
      the progression of tumors and their resistance to therapy. Sulfasalazine is an
      inhibitor of xCT that is known to increase cellular oxidative stress, giving it
      anti-tumor potential. Here, we describe a radio-sensitizing effect of
      sulfasalazine using a B16F10 melanoma model. Sulfasalazine decreased glutathione
      concentrations and resistance to H2O2 in B16F10 melanoma cells, but not in mouse
      embryonic fibroblasts. It synergistically enhanced the cyto-killing effect of X
      irradiation in B16F10 cells. It inhibited cellular DNA damage repair and
      prolonged cell cycle arrest after X-irradiation. Furthermore, in an in vivo
      transplanted melanoma model, sulfasalazine decreased intratumoral glutathione
      content, leading to enhanced susceptibility to radiation therapy. These results
      suggest the possibility of using SAS to augment the treatment of radio-resistant
      cancers.

PMID- 29649286
TI  - Correction: Dissecting the Autocrine and Paracrine Roles of the CCR2-CCL2 Axis in
      Tumor Survival and Angiogenesis.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0028305.].

PMID- 29649285
TI  - Cost of gastroenteritis in Australia: A healthcare perspective.
AB  - BACKGROUND: Acute gastroenteritis illness is a common illness that causes
      considerable morbidity, but current estimates of the cost to the Australian
      healthcare system are unknown. OBJECTIVE: To estimate the current healthcare
      utilisation and direct public healthcare system costs attributable to acute
      gastroenteritis illness in Australia. METHODS: This is an incidence-based cost-of
      illness study focused on quantifying direct health care costs using a bottom-up
      approach. Data on general practitioner consultations, prescribed medications,
      diagnostic tests, specialist consultations, emergency department visits and
      hospital admissions were collected from national reports. RESULTS: Using 2016
      prices, the estimated annual direct per capita cost of acute gastroenteritis
      illness was AUD$14.87 (USD$10.71), equating to AUD$20.27 (USD$14.59) per case.
      The estimated overall economic burden in Australia was AUD$359 million (USD$258
      million; AUD$1.5 million per 100,000 people). The major contributors to this cost
      were hospital admissions (57.1%), emergency department visits (17.7%), and
      general practitioner consultations (14.0%). Children under five years of age have
      the highest per capita rates of acute gastroenteritis illness; however, service
      utilisation rates vary by age group and both young children and older adults
      accounted for a substantial proportion of the overall economic burden
      attributable to acute gastroenteritis illness. CONCLUSIONS: Although chronic
      diseases comprise a large cost burden on the healthcare system, acute illnesses,
      including acute gastroenteritis illness, also impose substantial direct
      healthcare system costs. Providing data on current cost estimates is useful for
      prioritizing public health interventions, with our findings suggesting that it
      would be ideal if targeted interventions to reduce hospitalisation rates among
      young children and older adults were available.

PMID- 29649287
TI  - Viewing sexual images is associated with reduced physiological arousal response
      to gambling loss.
AB  - Erotic imagery is one highly salient emotional signal that exists everywhere in
      daily life. The impact of sexual stimuli on human decision-making, however, has
      rarely been investigated. This study examines the impact of sexual stimuli on
      financial decision-making under risk. In each trial, either a sexual or neutral
      image was presented in a picture categorization task before a gambling task.
      Thirty-four men made gambling decisions while their physiological arousal,
      measured by skin conductance responses (SCRs), was recorded. Behaviorally, the
      proportion of gambling decisions did not differ between the sexual and neutral
      image trials. Physiologically, participants had smaller arousal differences,
      measured in micro-siemen per dollar, between losses and gains in the sexual
      rather than in the neutral image trials. Moreover, participants' SCRs to losses
      relative to gains predicted the proportion of gambling decisions in the neutral
      image trials but not in the sexual image trials. The results were consistent with
      the hypothesis that the presence of emotionally salient sexual images reduces
      attentional and arousal-related responses to gambling losses. Our results are
      consistent with the theory of loss attention involving increased cognitive
      investment in losses compared to gains. The findings also have potential
      practical implications for our understanding of the specific roles of sexual
      images in human financial decision making in everyday life, such as gambling
      behaviors in the casino.

PMID- 29649288
TI  - Autofluorescence study and selected cyanidin quantification in the Jewel orchids
      Anoectochilus sp. and Ludisia discolor.
AB  - Anoectochilus sp. and Ludisia discolor are known as Jewel orchids. Both species
      are terrestrial wild orchids that grow in shaded areas of forests. The Jewel
      orchids are renowned for the beauty of their leaves, which are dark-green laced
      with silvery or golden veins. The orchids are used as a cure in various parts of
      Asia. Overharvesting and anthropogenic disturbances threaten the existence of the
      Jewel orchids in the wild, necessitating human intervention in their survival. An
      understanding of the structure and adaptations of a plant may assist in its
      survival when propagated outside of its habitat. In this study, ex vitro leaves
      of Anoectochilus sp. and L. discolor were subjected to freehand sectioning, and
      then inspected through brightfield and fluorescence microscopy. The study
      indicated that all parts of both plants presented typical monocotyledonous
      characteristics except the leaves. The leaves displayed dorsiventrality with
      distinct palisade and spongy mesophyll layers. The spongy mesophyll layer
      contained cells which fluoresced a bright red when exposed to ultraviolet, blue,
      and green light wavelengths, hinting at the presence of anthocyanins for
      photoprotection. Cyanidin was detected in the leaves of L. discolor, as
      enumerated through high performance liquid chromatography (HPLC). The
      observations indicated that Anoectochilus sp. and L. discolor are well-adapted to
      live under shaded conditions with minimal exposure to light.

PMID- 29649289
TI  - The best laid plans of mice and women.

PMID- 29649291
TI  - Expanding the genetic toolkit of Tribolium castaneum.
AB  - The red flour beetle, Tribolium castaneum, is an important model insect and
      agricultural pest. However, many standard genetic tools are lacking or
      underdeveloped in this system. Here, we present a set of new reagents to augment
      existing Tribolium genetic tools. We demonstrate a new GAL4 driver line that
      employs the promoter of a ribosomal protein gene to drive expression of a UAS
      responder in the fat body. We also present a novel dual fluorescent reporter that
      labels cell membranes and nuclei with different fluorophores for the analysis of
      cellular morphology. This approach also demonstrates the functionality of the
      viral T2A peptide for bicistronic gene expression in Tribolium. To facilitate
      classical genetic analysis, we created lines with visible genetic markers by
      CRISPR-mediated disruption of the yellow and ebony body color loci with a
      cassette carrying an attP site, enabling future phiC31-mediated integration.
      Together, the reagents presented here will facilitate more robust genetic
      analysis in Tribolium and serve as a blueprint for the further development of
      this powerful model's genetic toolkit.

PMID- 29649290
TI  - The contribution of gestational age, area deprivation and mother's country of
      birth to ethnic variations in infant mortality in England and Wales: A national
      cohort study using routinely collected data.
AB  - OBJECTIVES: We aimed to describe ethnic variations in infant mortality and
      explore the contribution of area deprivation, mother's country of birth, and
      prematurity to these variations. METHODS: We analyzed routine birth and death
      data on singleton live births (gestational age>=22 weeks) in England and Wales,
      2006-2012. Infant mortality by ethnic group was analyzed using logistic
      regression with adjustment for sociodemographic characteristics and gestational
      age. RESULTS: In the 4,634,932 births analyzed, crude infant mortality rates were
      higher in Pakistani, Black Caribbean, Black African, and Bangladeshi infants
      (6.92, 6.00, 5.17 and 4.40 per 1,000 live births, respectively vs. 2.87 in White
      British infants). Adjustment for maternal sociodemographic characteristics
      changed the results little. Further adjustment for gestational age strongly
      attenuated the risk in Black Caribbean (OR 1.02, 95% CI 0.89-1.17) and Black
      African infants (1.17, 1.06-1.29) but not in Pakistani (2.32, 2.15-2.50),
      Bangladeshi (1.47, 1.28-1.69), and Indian infants (1.24, 1.11-1.38). Ethnic
      variations in infant mortality differed significantly between term and preterm
      infants. At term, South Asian groups had higher risks which cannot be explained
      by sociodemographic characteristics. In preterm infants, adjustment for degree of
      prematurity (<28, 28-31, 32-33, 34-36 weeks) fully explained increased risks in
      Black but not Pakistani and Bangladeshi infants. Sensitivity analyses with
      further adjustment for small for gestational age, or excluding deaths due to
      congenital anomalies did not fully explain the excess risk in South Asian groups.
      CONCLUSIONS: Higher infant mortality in South Asian and Black infants does not
      appear to be explained by sociodemographic characteristics. Higher proportions of
      very premature infants appear to explain increased risks in Black infants but not
      in South Asian groups. Strategies targeting the prevention and management of
      preterm birth in Black groups and suboptimal birthweight and modifiable risk
      factors for congenital anomalies in South Asian groups might help reduce ethnic
      inequalities in infant mortality.

PMID- 29649292
TI  - Special Immunization Service: A 14-year experience in Italy.
AB  - BACKGROUND: Concerns regarding vaccine safety are increasing along with lack of
      compliance to vaccination schedules. This study aimed to assess vaccination
      related risks and the impact of a Special Immunization Service (SIS) at the
      Pediatric Emergency Department (PED) of Padua on vaccination compliance among
      participants. MATERIALS AND METHODS: This retrospective cohort study included all
      children attending the SIS from January 1st 2002 to December 31st 2015. The
      Service is divided into a clinic (SIS-C) where all referred children undergo a
      pre-vaccination visit and an area within the Pediatric Emergency Department (SIS
      PED) where children are vaccinated if indicated. During each SIS-C visit, age,
      gender, admission criteria and scheduled vaccinations were recorded, with any
      vaccine-related adverse events captured during SIS-PED visits. Follow-up was
      conducted to evaluate vaccination plan completion. RESULTS: 359 children received
      560 vaccine administrations (41.3% MMR/MMRV, 17.5% hexavalent) at the SIS during
      the 14 year study. Admission criteria were adverse events after previous
      vaccination (immediate, IgE/not IgE mediated, and late) in 27.2% of cases, non
      anaphylactic allergies (mostly egg allergy) in 42.7% and anaphylaxis in 10.3%.
      After vaccination, 15/560 (2.7%) mild adverse events were observed. 96.3% of
      children vaccinated at least once at the SIS-PED and available for follow-up
      completed their vaccination plan, in contrast to 55.5% of children referred to
      the SIS-C who were not vaccinated in SIS-PED. CONCLUSIONS: For children referred
      to SIS-C and available for follow-up, vaccination in SIS-PED was associated with
      more frequent completion of vaccination plans, indicating a benefit of the
      service to vaccine coverage. The low number and mild severity of adverse events
      reported after vaccination of high-risk children in SIS-PED attest to the safety
      of the service.

PMID- 29649294
TI  - Structural inference embedded adversarial networks for scene parsing.
AB  - Explicit structural inference is one key point to improve the accuracy of scene
      parsing. Meanwhile, adversarial training method is able to reinforce spatial
      contiguity in output segmentations. To take both advantages of the structural
      learning and adversarial training simultaneously, we propose a novel deep
      learning network architecture called Structural Inference Embedded Adversarial
      Networks (SIEANs) for pixel-wise scene labeling. The generator of our SIEANs, a
      novel designed scene parsing network, makes full use of convolutional neural
      networks and long short-term memory networks to learn the global contextual
      information of objects in four different directions from RGB-(D) images, which is
      able to describe the (three-dimensional) spatial distributions of objects in a
      more comprehensive and accurate way. To further improve the performance, we
      explore the adversarial training method to optimize the generator along with a
      discriminator, which can not only detect and correct higher-order inconsistencies
      between the predicted segmentations and corresponding ground truths, but also
      exploit full advantages of the generator by fine-tuning its parameters so as to
      obtain higher consistencies. The experimental results demonstrate that our
      proposed SIEANs is able to achieve a better performance on PASCAL VOC 2012, SIFT
      FLOW, PASCAL Person-Part, Cityscapes, Stanford Background, NYUDv2, and SUN-RGBD
      datasets compared to the most of state-of-the-art methods.

PMID- 29649293
TI  - Inducing cell death in vitro in cancer cells by targeted delivery of cytochrome c
      via a transferrin conjugate.
AB  - One of the major drawbacks of many of the currently used cancer drugs are off
      target effects. Targeted delivery is one method to minimize such unwanted and
      detrimental events. To actively target lung cancer cells, we have developed a
      conjugate of the apoptosis inducing protein cytochrome c with transferrin because
      the transferrin receptor is overexpressed by many rapidly dividing cancer cells.
      Cytochrome c and transferrin were cross-linked with a redox sensitive disulfide
      bond for the intra-cellular release of the protein upon endocytosis by the
      transferrin receptor. Confocal results demonstrated the cellular uptake of the
      cytochrome c-transferrin conjugate by transferrin receptor overexpressing A549
      lung cancer cells. Localization studies further validated that this conjugate
      escaped the endosome. Additionally, an in vitro assay showed that the conjugate
      could induce apoptosis by activating caspase-3. The neo-conjugate not only
      maintained an IC50 value similar to the well known drug cisplatin (50 MUM) in
      A549 cancer cells but also was nontoxic to the normal lung (MRC5) cells. Our neo
      conjugate holds promise for future development to target cancers with enhanced
      transferrin receptor expression.

PMID- 29649295
TI  - Correction: Karyotype evolution in Phalaris (Poaceae): The role of reductional
      dysploidy, polyploidy and chromosome alteration in a wide-spread and diverse
      genus.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0192869.].

PMID- 29649296
TI  - Host shifts result in parallel genetic changes when viruses evolve in closely
      related species.
AB  - Host shifts, where a pathogen invades and establishes in a new host species, are
      a major source of emerging infectious diseases. They frequently occur between
      related host species and often rely on the pathogen evolving adaptations that
      increase their fitness in the novel host species. To investigate genetic changes
      in novel hosts, we experimentally evolved replicate lineages of an RNA virus
      (Drosophila C Virus) in 19 different species of Drosophilidae and deep sequenced
      the viral genomes. We found a strong pattern of parallel evolution, where viral
      lineages from the same host were genetically more similar to each other than to
      lineages from other host species. When we compared viruses that had evolved in
      different host species, we found that parallel genetic changes were more likely
      to occur if the two host species were closely related. This suggests that when a
      virus adapts to one host it might also become better adapted to closely related
      host species. This may explain in part why host shifts tend to occur between
      related species, and may mean that when a new pathogen appears in a given
      species, closely related species may become vulnerable to the new disease.

PMID- 29649298
TI  - Haemophilus ducreyi cutaneous ulcer contracted at Seram Island, Indonesia,
      presented in the Netherlands.
AB  - OVERVIEW: We describe the first case of a cutaneous ulcer caused by Haemophilus
      ducreyi imported from Indonesia to the Netherlands. Skin infections caused by H.
      ducreyi are uncommon in travellers and have been described in just a few case
      reports and were all contracted on the Pacific Islands. THE CASE: A 22-year-old
      healthy male visited the Center of Tropical Medicine and Travel Medicine in
      February 2017 with a cutaneous ulcer of the right lateral malleolus 4 weeks after
      returning from Indonesia (Seram and Ambon Islands). He had noticed a small skin
      abrasion on the right ankle after slipping on a rock during a jungle trip on
      Seram Island. Back in the Netherlands, a painful ulcer developed at the same body
      location, and despite treatment with flucloxacillin, his complaints worsened. A
      swab that was taken for culture showed growth of small grey colonies that were
      characterised as H. ducreyi with matrix-assisted laser desorption/ionisation time
      of-flight (MALDI-TOF) mass spectrometry. Treatment with ciprofloxacin for the
      diagnosis of H. ducreyi cutaneous ulcer was started, and the ulcer clearly
      diminished, leaving only a small healing ulcer. DISCUSSION: H. ducreyi is
      normally the causative agent of genital ulcers but is increasingly recognised as
      a cause of chronic skin ulcers, e.g., in Papua New Guinea. In our patient, the
      infection was very likely contracted in the Maluku province of Indonesia and
      imported into the Netherlands. No reports of infection with H. ducreyi from
      Indonesia could be found in literature, but this case indicates that H. ducreyi
      is present in at least one of the northeastern islands of Indonesia, which is
      important for local healthcare. Additionally, it illustrates the role of this
      agent as a cause of cutaneous ulcers in previously healthy travellers.

PMID- 29649300
TI  - Modeling joint restoration strategies for interdependent infrastructure systems.
AB  - Life in the modern world depends on multiple critical services provided by
      infrastructure systems which are interdependent at multiple levels. To
      effectively respond to infrastructure failures, this paper proposes a model for
      developing optimal joint restoration strategy for interdependent infrastructure
      systems following a disruptive event. First, models for (i) describing structure
      of interdependent infrastructure system and (ii) their interaction process, are
      presented. Both models are considering the failure types, infrastructure
      operating rules and interdependencies among systems. Second, an optimization
      model for determining an optimal joint restoration strategy at infrastructure
      component level by minimizing the economic loss from the infrastructure failures,
      is proposed. The utility of the model is illustrated using a case study of
      electric-water systems. Results show that a small number of failed infrastructure
      components can trigger high level failures in interdependent systems; the optimal
      joint restoration strategy varies with failure occurrence time. The proposed
      models can help decision makers to understand the mechanisms of infrastructure
      interactions and search for optimal joint restoration strategy, which can
      significantly enhance safety of infrastructure systems.

PMID- 29649299
TI  - Digitization of natural objects with micro CT and photographs.
AB  - In this paper, we present a three-dimensional (3D) digitization technique for
      natural objects, such as insects and plants. The key idea is to combine X-ray
      computed tomography (CT) and photographs to obtain both complicated 3D shapes and
      surface textures of target specimens. We measure a specimen by using an X-ray CT
      device and a digital camera to obtain a CT volumetric image (volume) and multiple
      photographs. We then reconstruct a 3D model by segmenting the CT volume and
      generate a texture by projecting the photographs onto the model. To achieve this
      reconstruction, we introduce a technique for estimating a camera position for
      each photograph. We also present techniques for merging multiple textures
      generated from multiple photographs and recovering missing texture areas caused
      by occlusion. We illustrate the feasibility of our 3D digitization technique by
      digitizing 3D textured models of insects and flowers. The combination of X-ray CT
      and a digital camera makes it possible to successfully digitize specimens with
      complicated 3D structures accurately and allows us to browse both surface colors
      and internal structures.

PMID- 29649297
TI  - Diversity of cultivable fungal endophytes in Paullinia cupana (Mart.) Ducke and
      bioactivity of their secondary metabolites.
AB  - Paullinia cupana is associated with a diverse community of pathogenic and
      endophytic microorganisms. We isolated and identified endophytic fungal
      communities from the roots and seeds of P. cupana genotypes susceptible and
      tolerant to anthracnose that grow in two sites of the Brazilian Amazonia forest.
      We assessed the antibacterial, antitumor and genotoxic activity in vitro of
      compounds isolated from the strains Trichoderma asperellum (1BDA) and Diaporthe
      phaseolorum (8S). In concert, we identified eight fungal species not previously
      reported as endophytes; some fungal species capable of inhibiting pathogen
      growth; and the production of antibiotics and compounds with bacteriostatic
      activity against Pseudomonas aeruginosa in both susceptible and multiresistant
      host strains. The plant genotype, geographic location and specially the organ
      influenced the composition of P. cupana endophytic fungal community. Together,
      our findings identify important functional roles of endophytic species found
      within the microbiome of P. cupana. This hypothesis requires experimental
      validation to propose management of this microbiome with the objective of
      promoting plant growth and protection.

PMID- 29649301
TI  - pyBadlands: A framework to simulate sediment transport, landscape dynamics and
      basin stratigraphic evolution through space and time.
AB  - Understanding Earth surface responses in terms of sediment dynamics to climatic
      variability and tectonics forcing is hindered by limited ability of current
      models to simulate long-term evolution of sediment transfer and associated
      morphological changes. This paper presents pyBadlands, an open-source python
      based framework which computes over geological time (1) sediment transport from
      landmasses to coasts, (2) reworking of marine sediments by longshore currents and
      (3) development of coral reef systems. pyBadlands is cross-platform, distributed
      under the GPLv3 license and available on GitHub (http://github.com/badlands
      model). Here, we describe the underlying physical assumptions behind the
      simulated processes and the main options already available in the numerical
      framework. Along with the source code, a list of hands-on examples is provided
      that illustrates the model capabilities. In addition, pre and post-processing
      classes have been built and are accessible as a companion toolbox which comprises
      a series of workflows to efficiently build, quantify and explore simulation input
      and output files. While the framework has been primarily designed for research,
      its simplicity of use and portability makes it a great tool for teaching
      purposes.

PMID- 29649302
TI  - Identifying tumor in pancreatic neuroendocrine neoplasms from Ki67 images using
      transfer learning.
AB  - The World Health Organization (WHO) has clear guidelines regarding the use of
      Ki67 index in defining the proliferative rate and assigning grade for pancreatic
      neuroendocrine tumor (NET). WHO mandates the quantification of Ki67 index by
      counting at least 500 positive tumor cells in a hotspot. Unfortunately, Ki67
      antibody may stain both tumor and non-tumor cells as positive depending on the
      phase of the cell cycle. Likewise, the counter stain labels both tumor and non
      tumor as negative. This non-specific nature of Ki67 stain and counter stain
      therefore hinders the exact quantification of Ki67 index. To address this
      problem, we present a deep learning method to automatically differentiate between
      NET and non-tumor regions based on images of Ki67 stained biopsies. Transfer
      learning was employed to recognize and apply relevant knowledge from previous
      learning experiences to differentiate between tumor and non-tumor regions.
      Transfer learning exploits a rich set of features previously used to successfully
      categorize non-pathology data into 1,000 classes. The method was trained and
      validated on a set of whole-slide images including 33 NETs subject to Ki67
      immunohistochemical staining using a leave-one-out cross-validation. When applied
      to 30 high power fields (HPF) and assessed against a gold standard (evaluation by
      two expert pathologists), the method resulted in a high sensitivity of 97.8% and
      specificity of 88.8%. The deep learning method developed has the potential to
      reduce pathologists' workload by directly identifying tumor boundaries on images
      of Ki67 stained slides. Moreover, it has the potential to replace sophisticated
      and expensive imaging methods which are recently developed for identification of
      tumor boundaries in images of Ki67-stained NETs.

PMID- 29649303
TI  - A new diatom species P. hallegraeffii sp. nov. belonging to the toxic genus
      Pseudo-nitzschia (Bacillariophyceae) from the East Australian Current.
AB  - A new species belonging to the toxin producing diatom genus Pseudo-nitzschia, P.
      hallegraeffii sp. nov., is delineated and described from the East Australian
      Current (EAC). Clonal cultures were established by single cell isolation from
      phytoplankton net hauls collected as part of a research expedition in the EAC
      region in 2016 on the RV Investigator. Cultures were assessed for their
      morphological and genetic characteristics, their sexual compatibility with other
      Pseudo-nitzschia species, and their ability to produce domoic acid. Light and
      transmission electron microscopy revealed cells which differed from their closest
      relatives by their cell width, rows of poroids, girdle band structure and density
      of band straie. Phylogenetic analyses based on sequencing of nuclear-encoded
      ribosomal deoxyribonucleic acid (rDNA) regions showed this novel genotype
      clustered within the P. delicatissima complex, but formed a discrete clade from
      its closest relatives P. dolorosa, P. simulans, P. micropora and P.
      delicatissima. Complementary base changes (CBCs) were observed in the secondary
      structure of the 3' nuclear ribosomal transcribed spacer sequence region (ITS2)
      between P. hallegraeffii sp. nov. and its closest related taxa, P. simulans and
      P. dolorosa. Under laboratory conditions, and in the absence of any zooplankton
      cues, strains of P. hallegraeffii sp. nov. did not produce domoic acid (DA) and
      were not sexually compatible with any other Pseudo-nitzschia clones tested. A
      total of 18 Pseudo-nitzschia species, including three confirmed toxigenic species
      (P. cuspidata, P. multistriata and P. australis) have now been unequivocally
      confirmed from eastern Australia.

PMID- 29649304
TI  - Sedentary behavior associated with reduced medial temporal lobe thickness in
      middle-aged and older adults.
AB  - Atrophy of the medial temporal lobe (MTL) occurs with aging, resulting in
      impaired episodic memory. Aerobic fitness is positively correlated with total
      hippocampal volume, a heavily studied memory-critical region within the MTL.
      However, research on associations between sedentary behavior and MTL subregion
      integrity is limited. Here we explore associations between thickness of the MTL
      and its subregions (namely CA1, CA23DG, fusiform gyrus, subiculum,
      parahippocampal, perirhinal and entorhinal cortex,), physical activity, and
      sedentary behavior. We assessed 35 non-demented middle-aged and older adults (25
      women, 10 men; 45-75 years) using the International Physical Activity
      Questionnaire for older adults, which quantifies physical activity levels in MET
      equivalent units and asks about the average number of hours spent sitting per
      day. All participants had high resolution MRI scans performed on a Siemens
      Allegra 3T MRI scanner, which allows for detailed investigation of the MTL.
      Controlling for age, total MTL thickness correlated inversely with hours of
      sitting/day (r = -0.37, p = 0.03). In MTL subregion analysis, parahippocampal (r
      = -0.45, p = 0.007), entorhinal (r = -0.33, p = 0.05) cortical and subiculum (r =
      -0.36, p = .04) thicknesses correlated inversely with hours of sitting/day. No
      significant correlations were observed between physical activity levels and MTL
      thickness. Though preliminary, our results suggest that more sedentary non
      demented individuals have less MTL thickness. Future studies should include
      longitudinal analyses and explore mechanisms, as well as the efficacy of
      decreasing sedentary behaviors to reverse this association.

PMID- 29649305
TI  - Disabling of lymphocyte immune response by Ebola virus.

PMID- 29649306
TI  - Single camera multi-view anthropometric measurement of human height and mid-upper
      arm circumference using linear regression.
AB  - BACKGROUND: Manually measured anthropometric quantities are used in many
      applications including human malnutrition assessment. Training is required to
      collect anthropometric measurements manually, which is not ideal in resource
      constrained environments. Photogrammetric methods have been gaining attention in
      recent years, due to the availability and affordability of digital cameras.
      OBJECTIVE: The primary goal is to demonstrate that height and mid-upper arm
      circumference (MUAC)-indicators of malnutrition-can be accurately estimated by
      applying linear regression to distance measurements from photographs of
      participants taken from five views, and determine the optimal view combinations.
      A secondary goal is to observe the effect on estimate error of two approaches
      which reduce complexity of the setup, computational requirements and the
      expertise required of the observer. METHODS: Thirty-one participants (11 female,
      20 male; 18-37 years) were photographed from five views. Distances were computed
      using both camera calibration and reference object techniques from manually
      annotated photos. To estimate height, linear regression was applied to the
      distances between the top of the participants head and the floor, as well as the
      height of a bounding box enclosing the participant's silhouette which eliminates
      the need to identify the floor. To estimate MUAC, linear regression was applied
      to the mid-upper arm width. Estimates were computed for all view combinations and
      performance was compared to other photogrammetric methods from the literature
      linear distance method for height, and shape models for MUAC. RESULTS: The mean
      absolute difference (MAD) between the linear regression estimates and manual
      measurements were smaller compared to other methods. For the optimal view
      combinations (smallest MAD), the technical error of measurement and coefficient
      of reliability also indicate the linear regression methods are more reliable. The
      optimal view combination was the front and side views. When estimating height by
      linear regression of the distance from the head to the floor, the mean MAD was
      10.51 mm +/- 6.52 mm SD, and when estimating height from the bounding box using
      the reference object, the mean MAD per participant was 11.53 mm +/- 6.43 mm SD.
      When estimating MUAC from the mid-upper arm radius using the reference object,
      the mean MAD was 7.24 mm +/- 4.79 mm SD. The mean MAD for all methods when using
      camera calibration was 2-3 mm smaller. CONCLUSIONS: Applying linear regression to
      distance measurements from photos of adults taken from multiple view angles has
      been shown to accurately estimate height and MUAC to within the accuracy required
      for nutrition assessment. Future work will focus on automating the landmark
      detection, and validating the methods on populations that include undernourished
      adults and children of all nutrition statuses. These future works will improve
      the practicality of this method as a potential tool for nutrition assessment by
      novice users.

PMID- 29649307
TI  - Bilateral carotid artery stenosis causes unexpected early changes in brain
      extracellular matrix and blood-brain barrier integrity in mice.
AB  - Bilateral carotid artery stenosis (BCAS) is one experimental model of vascular
      dementia thought to preferentially impact brain white matter. Indeed, few studies
      report hippocampal and cortical pathology prior to 30 days post-stenosis; though
      it is unclear whether those studies examined regions outside the white matter.
      Since changes in the blood-brain barrier (BBB) permeability precede more overt
      brain pathology in various diseases, we hypothesized that changes within the BBB
      and/or BBB-associated extracellular matrix (ECM) could occur earlier after BCAS
      in the hippocampus, cortex and striatum and be a precursor of longer term
      pathology. Here, C57Bl/6 mice underwent BCAS or sham surgeries and changes in the
      BBB and ECM were analyzed by collagen IV (vascular basement membrane component),
      alpha5 integrin (marker of endothelial activation), claudin-5 and occludin (tight
      junction proteins), Evans blue (permeability marker), Ki-67 (cell proliferation
      marker), and GFAP and CD11b (glial cell markers) immunohistochemistry after 14
      days. Significant changes in markers of cerebrovascular integrity and glial
      activation were detected, not only in the striatum, but also in the hippocampus
      and cortex. In conclusion, this study demonstrates for the first time that
      changes in the BBB/ECM occur shortly after BCAS and within multiple brain regions
      and suggests such changes might underlie the gradual development of BCAS non
      white matter pathology.

PMID- 29649308
TI  - Subtyping of Clostridium difficile PCR ribotypes 591, 106 and 002, the dominant
      strain types circulating in Medellin, Colombia.
AB  - We aimed to achieve a higher typing resolution within the three dominant
      Clostridium difficile ribotypes (591,106 and 002) circulating in Colombia. A
      total of 50 C. difficile isolates we had previously typed by PCR-ribotyping,
      representing the major three ribotypes circulating in Colombia, were analyzed.
      Twenty-seven isolates of ribotype 591, 12 of ribotype 106 and 11 of ribotype 002
      were subtyped by multiple locus variable-number tandem-repeat analysis (MLVA).
      The presence of the PaLoc genes (tcdA/tcdB), toxin production in culture and
      antimicrobial susceptibility were also determined. From the total C. difficile
      ribotypes analyzed, 20 isolates (74%) of ribotype 591, nine (75%) of ribotype 106
      and five (45.5%) of ribotype 002 were recovered from patients with Clostridium
      difficile infection (CDI). MLVA allowed us to recognize four and two different
      clonal complexes for ribotypes 591 and 002, respectively, having a summed tandem
      repeat difference (STRD) <2, whereas none of the ribotype 106 isolates were
      grouped in a cluster or clonal complex having a STRD >10. Six ribotype 591 and
      three ribotype 002 isolates belonging to a defined clonal complex were isolated
      on the same week in two different hospitals. All ribotypes harbored either
      tcdA+/tcdB+ or tcdA-/tcdB+ PaLoc genes. Moreover, 94% of the isolates were
      positive for toxin in culture. All isolates were susceptible to vancomycin and
      metronidazole, while 75% to 100% of the isolates were resistant to clindamycin,
      and less than 14.8% of ribotype 591 isolates were resistant to moxifloxacina. No
      significant differences were found among ribotypes with respect to demographic
      and clinical patients' data; however, our results demonstrated a high molecular
      heterogeneity of C. difficile strains circulating in Colombia.

PMID- 29649309
TI  - High quality of life, treatment tolerability, safety and efficacy in HIV patients
      switching from triple therapy to lopinavir/ritonavir monotherapy: A randomized
      clinical trial.
AB  - TRIAL DESIGN: The QoLKAMON study evaluated quality of life, efficacy and
      treatment safety in HIV patients receiving lopinavir/ritonavir in monotherapy
      (MT) versus continuing combined antiretroviral triple treatment with a boosted
      protease inhibitor (TT). METHODS: This was a 24-week, open-label, multicentre
      study in virologically-suppressed HIV-infected participants (N = 225) with a 2:1
      randomization: 146 patients who switched to MT were compared with 79 patients who
      remained on a TT regimen. The primary endpoint was change in patient-reported
      outcomes in quality of life as measured by the MOS-HIV and EQ-5D questionnaires.
      Secondary endpoints included treatment adherence, patient satisfaction, incidence
      of adverse events and differences in plasma HIV-1 RNA viral load (VL) and CD4
      cell counts. RESULTS: Baseline quality of life, measured with the MOS-HIV score,
      was very good (overall score of 83 +/- 10.5 in the MT arm and 82.3 +/- 11.3 in
      the TT arm) and suffered no change during the study in any of the arms (at week
      24, 83.5 +/- 12.2 in MT arm and 81.9 +/- 12.7 in TT arm), without statistically
      significant differences when compared. In regards to adherence to therapy and
      patient satisfaction, some aspects (number of doses forgotten in the last week
      and satisfaction of treatment measured with the CESTA score, dimension 1)
      improved significantly with MT. There were also no differences in the incidence
      and severity of adverse events, even though 22.8% of those in the MT arm switched
      their treatment when they were included in the study. Moreover, there was also no
      significant difference between the immunological and virological evolution of MT
      and TT. In the MT arm, the VL was always undetectable in 83% of patients (vs
      90.7% in the TT arm) and there were only 6.7% of virological failures with VL >
      50 copies/mL (vs 2.3% in the TT arm), without resistance mutations and with
      resuppression of VL after switching back to TT. CONCLUSIONS: In a new clinical
      trial, monotherapy as a treatment simplification strategy in HIV-1 infected
      patients with sustained viral suppression has demonstrated quality of life,
      safety and efficacy profiles comparable to those of conventional triple therapy
      regimens.

PMID- 29649311
TI  - Correction: High prevalence of elevated blood lead levels in both rural and urban
      Iowa newborns: Spatial patterns and area-level covariates.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0177930.].

PMID- 29649310
TI  - Administration of oral fluoroquinolone and the risk of rhegmatogenous retinal
      detachment: A nationwide population-based study in Korea.
AB  - PURPOSE: To investigate the association between oral fluoroquinolones (FQ) and
      the risk of rhegmatogenous retinal detachment (RRD) using a nationwide population
      based study in Korea, designed to control for time-related bias. METHODS: As a
      nested case-control study within a cohort, the KNHIS-NSC 2002-2013 (Korean
      National Health Insurance Service National Sample Cohort) data used for the
      investigation. The subjects who visited an ophthalmologist were included in a
      cohort. Subjects with infectious ocular diseases, severe ocular trauma, and
      congenital diseases were excluded. Within the cohort, subjects who underwent
      surgery for RRD were defined as cases, and controls were matched by age group,
      sex, and cohort entry date using an incidence density sampling method. After
      investigating the exposure to oral FQ, the odds ratio was calculated by the FQ
      exposure rate of both groups and adjusted by the confounding factors of
      demography, health service utilization, and comorbidities. RESULTS: A total of
      1,151 subjects in the case group and 11,470 subjects in the control group were
      included. There were intergroup differences in household income, numbers of
      ophthalmologic visits and drug prescriptions, events of intraocular surgeries,
      and prevalence of diabetes and degenerative myopia (all P's<0.05). The crude odds
      ratio of the total group was 1.06 (P = 0.53, 95% CI 0.88-1.28), and the odds
      ratio adjusted for all pre-defined confounders was 1.00 (P = 0.99, 95% CI 0.81
      1.24). The crude and adjusted odds ratios were not showed statistical
      significance (all P's>0.05). CONCLUSIONS: By the nested case-control design, this
      study showed that oral administration of FQ was not associated with the increased
      risk of development of RRD.

PMID- 29649312
TI  - Iowa stream nitrate and the Gulf of Mexico.
AB  - The main objective of this work was to quantify and update the U.S. Midwest
      agricultural state of Iowa's contribution of nitrate-nitrogen to the Mississippi
      River stream network against the backdrop of the ongoing problem of Gulf of
      Mexico hypoxia. To achieve this objective, we used stream nitrate and discharge
      data collected from 1999 until 2016 at 23 Iowa stream sites near watershed
      outlets, along with publicly-available data for sites downstream of Iowa on the
      Missouri and Mississippi Rivers. Our analysis shows that Iowa contributes between
      11 and 52% of the long-term nitrate load to the Mississippi-Atchafalaya Basin, 20
      to 63% to the Upper Mississippi River Basin, and 20 to 89% to the Missouri River
      Basin, with averages of 29, 45 and 55% respectively. Since 1999, nitrate loads in
      the Iowa-inclusive basins have increased and these increases do not appear to be
      driven by changes in discharge and cropping intensity unique to Iowa. The 5-year
      running annual average of Iowa nitrate loading has been above the 2003 level for
      ten consecutive years, implying that Gulf hypoxic areal goals, also based on a 5
      year running annual average, will be very difficult to achieve if nitrate
      retention cannot be improved in Iowa. An opportunity exists for land managers,
      policy makers and conservationists to manifest a positive effect on water quality
      by targeting and implementing nitrate reducing-practices in areas like Iowa while
      avoiding areas that are less likely to affect Gulf of Mexico hypoxia.

PMID- 29649314
TI  - Randomly auditing research labs could be an affordable way to improve research
      quality: A simulation study.
AB  - The "publish or perish" incentive drives many researchers to increase the
      quantity of their papers at the cost of quality. Lowering quality increases the
      number of false positive errors which is a key cause of the reproducibility
      crisis. We adapted a previously published simulation of the research world where
      labs that produce many papers are more likely to have "child" labs that inherit
      their characteristics. This selection creates a competitive spiral that favours
      quantity over quality. To try to halt the competitive spiral we added random
      audits that could detect and remove labs with a high proportion of false
      positives, and also improved the behaviour of "child" and "parent" labs who
      increased their effort and so lowered their probability of making a false
      positive error. Without auditing, only 0.2% of simulations did not experience the
      competitive spiral, defined by a convergence to the highest possible false
      positive probability. Auditing 1.35% of papers avoided the competitive spiral in
      71% of simulations, and auditing 1.94% of papers in 95% of simulations. Audits
      worked best when they were only applied to established labs with 50 or more
      papers compared with labs with 25 or more papers. Adding a +/-20% random error to
      the number of false positives to simulate peer reviewer error did not reduce the
      audits' efficacy. The main benefit of the audits was via the increase in effort
      in "child" and "parent" labs. Audits improved the literature by reducing the
      number of false positives from 30.2 per 100 papers to 12.3 per 100 papers.
      Auditing 1.94% of papers would cost an estimated $15.9 million per year if
      applied to papers produced by National Institutes of Health funding. Our
      simulation greatly simplifies the research world and there are many unanswered
      questions about if and how audits would work that can only be addressed by a
      trial of an audit.

PMID- 29649315
TI  - Retailer Stackelberg game in a supply chain with pricing and service decisions
      and simple price discount contract.
AB  - This paper studies the Retailer Stackelberg game in a supply chain consisting of
      two manufacturers and one retailer where they compete simultaneously under three
      factors including price, service and simple price discount contract. It is
      assumed that the second manufacturer provides service directly to his customers,
      and the retailer provides service for the first product's customers, while the
      retailer buys the first product under price discount from the first manufacturer.
      The analysis of the optimal equilibrium solutions and the results of the
      numerical examples show that if a manufacturer chooses the appropriate range of
      discount rate, he will gain more profit than when there is no discount given to
      the retailer. This situation can be considered as an effective tool for the
      coordination of the first manufacturer and the retailer to offer discount by
      manufacturer and to provide the service by the retailer. We obtain equilibrium
      solution of Retailer Stackelberg game and analyze the numerical examples under
      two cases: a) the manufacturers sell their products to the retailer without price
      discount contract. b) The first manufacturer sells his products to the retailer
      with the simple price discount contract. The preliminary results show that the
      service and the price discount contract can improve the performance of supply
      chain.

PMID- 29649313
TI  - Serosurveillance of Coxiellosis (Q-fever) and Brucellosis in goats in selected
      provinces of Lao People's Democratic Republic.
AB  - Goat raising is a growing industry in Lao People's Democratic Republic, with
      minimal disease investigation to date, especially zoonoses. This study determined
      the proportional seropositivity of two zoonotic diseases: Q fever (causative
      agent Coxiella burnetii) and Brucellosis (Brucella species) in goats across five
      provinces (Vientiane Capital, Xayaboury, Xiengkhuang, Savannakhet and Attapeu). A
      total of 1458 goat serum samples were tested using commercial indirect ELISA for
      both pathogens, plus Rose Bengal agglutination test for Brucellosis. Overall
      individual seropositivity of C. burnetii was 4.1% and Brucella spp. was 1.4%. A
      multiple logistic regression model identified that province (Vientiane Capital, p
      = 0.05), breed (introduced Boer mixed breed, p = 0.006) and age (goats >=3 years
      old, p = 0.014) were significant risk factors for C. burnetii seropositivity. The
      results of the survey indicated that province (Vientiane Capital, p<0.001), breed
      (introduced Boer mixed breed, p<0.001), production system (commercial, p<0.001),
      age (adult, p = 0.004), and farm size (large, 0.001) were all significant risk
      factors seropositivity for Brucella spp. It was concluded that Lao goats have
      been exposed to both C. burnetii and Brucella spp. however the risk of clinical
      disease has not yet been determined and there is an urgent need to determine
      human health risks and economic losses caused by Q fever and Brucellosis.

PMID- 29649316
TI  - Effect of one-lung ventilation on end-tidal carbon dioxide during cardiopulmonary
      resuscitation in a pig model of cardiac arrest.
AB  - Unrecognized endobronchial intubation frequently occurs after emergency
      intubation. However, no study has evaluated the effect of one-lung ventilation on
      end-tidal carbon dioxide (ETCO2) during cardiopulmonary resuscitation (CPR). We
      compared the hemodynamic parameters, blood gases, and ETCO2 during one-lung
      ventilation with those during conventional two-lung ventilation in a pig model of
      CPR, to determine the effect of the former on ETCO2. A randomized crossover study
      was conducted in 12 pigs intubated with double-lumen endobronchial tube to
      achieve lung separation. During CPR, the animals underwent three 5-min
      ventilation trials based on a randomized crossover design: left-lung, right-lung,
      or two-lung ventilation. Arterial blood gases were measured at the end of each
      ventilation trial. Ventilation was provided using the same tidal volume
      throughout the ventilation trials. Comparison using generalized linear mixed
      model revealed no significant group effects with respect to aortic pressure,
      coronary perfusion pressure, and carotid blood flow; however, significant group
      effect in terms of ETCO2 was found (P < 0.001). In the post hoc analyses, ETCO2
      was lower during the right-lung ventilation than during the two-lung (P = 0.006)
      or left-lung ventilation (P < 0.001). However, no difference in ETCO2 was
      detected between the left-lung and two-lung ventilations. The partial pressure of
      arterial carbon dioxide (PaCO2), partial pressure of arterial oxygen (PaO2), and
      oxygen saturation (SaO2) differed among the three types of ventilation (P =
      0.003, P = 0.001, and P = 0.001, respectively). The post hoc analyses revealed a
      higher PaCO2, lower PaO2, and lower SaO2 during right-lung ventilation than
      during two-lung or left-lung ventilation. However, the levels of these blood
      gases did not differ between the left-lung and two-lung ventilations. In a pig
      model of CPR, ETCO2 was significantly lower during right-lung ventilation than
      during two-lung ventilation. However, interestingly, ETCO2 during left-lung
      ventilation was comparable to that during two-lung ventilation.

PMID- 29649317
TI  - 'I could not join because I had to work for pay.': A qualitative evaluation of
      falciparum malaria pro-active case detection in three rural Cambodian villages.
AB  - BACKGROUND: Pro-active case detection (Pro-ACD), in the form of voluntary
      screening and treatment (VSAT) following community mobilisation about
      'asymptomatic malaria', is currently being evaluated as a tool for Plasmodium
      falciparum elimination in Preah Vihear Province, Cambodia. METHODS: A qualitative
      study was conducted to explore community understanding, perceptions, expectations
      and acceptability of the Pro-ACD intervention in order to identify aspects that
      could be improved in future Pro-ACD activities. This was ancillary to a three
      round VSAT campaign, carried out in three villages between December 2015 and
      March 2016. Qualitative data collection began shortly after the end of the three
      rounds of screening. Purposive sampling was used to select participants. Nine
      focus group discussions with participants (n = 46) and non-participants (n = 40)
      in the Pro-ACD screening were conducted, in addition to in-depth interviews with
      key village figures (n = 9). RESULTS: Health promotion messages were well
      delivered and received, but it was difficult for many villagers to understand the
      messages around 'asymptomatic malaria'. Overall, villagers and village leaders
      had a positive opinion about the VSAT intervention. Acceptability was high, as a
      direct consequence of favourable perceptions towards the screening activity: the
      Pro-ACD intervention was seen by the local population as an effective,
      inexpensive, reliable and readily available tool to protect individuals and the
      community from the insurgence of malaria. Physical absence and lack of time (both
      linked to work-related activities) were the main reasons for non-participation.
      CONCLUSIONS: Although VSAT was generally well perceived and accepted, the 'time
      factor' related to the need to satisfy essential daily subsistence requirements
      played a significant role in determining participation in the screening. More
      well-adapted and meaningful Pro-ACD approaches could be implemented by improving
      the timing of the testing activites, and strengthening community participation
      and engagement to increase acceptability.

PMID- 29649318
TI  - Confined placental mosaicism revisited: Impact on pregnancy characteristics and
      outcome.
AB  - OBJECTIVES: We wanted to re-evaluate the influence of confined placental
      mosaicism subtypes (type 2 and type 3) on pregnancy characteristics and outcome.
      MATERIAL AND METHODS: From July 2009 to December 2015, 5512 chorionic villus
      samplings were performed in our Fetal Medicine Center. Conventional karyotyping
      was performed after long-term and short-term cultured villi to define type 2 or
      type 3 confined placental mosaicisms. Karyotype after amniocentesis was performed
      to exclude true fetal mosaicism, when appropriate. Pregnancy characteristics and
      outcomes were collected and compared to a control population. RESULTS: Thirty-six
      (0.65%) confined placental mosaicisms were observed (13 type 2 and 23 type 3).
      Nuchal translucency was not increased for type 2 and type 3 confined placental
      mosaicisms. Pregnancy characteristics and outcomes were comparable between type 2
      confined placental mosaicisms and the control population. In type 3 confined
      placental mosaicisms, median first trimester serum pregnancy-associated plasma
      protein A was lower than for the control population (p<0.001), preterm births
      were noticed in 56% (p<0.001), small for gestational age newborns in 74%
      (p<0.001), and adverse pregnancy outcome was reported in 35% (p<0.01).
      CONCLUSION: Although type 2 confined placental mosaicisms appeared to have no
      influence on pregnancy characteristics and outcome, type 3 confined placental
      mosaicisms were associated with low levels of first trimester serum pregnancy
      associated plasma protein A, preterm birth, small for gestational age newborns,
      and adverse pregnancy outcomes.

PMID- 29649319
TI  - Unraveling endothelin-1 induced hypercontractility of human pulmonary artery
      smooth muscle cells from patients with pulmonary arterial hypertension.
AB  - Contraction of human pulmonary artery smooth muscle cells (HPASMC) isolated from
      pulmonary arterial hypertensive (PAH) and normal (non-PAH) subject lungs was
      determined and measured with real-time electrical impedance. Treatment of HPASMC
      with vasoactive peptides, endothelin-1 (ET-1) and bradykinin (BK) but not
      angiotensin II, induced a temporal decrease in the electrical impedance profile
      mirroring constrictive morphological change of the cells which typically was more
      robust in PAH as opposed to non-PAH cells. Inhibition with LIMKi3 and a cofilin
      targeted motif mimicking cell permeable peptide (MMCPP) had no effect on ET-1
      induced HPASMC contraction indicating a negligible role for these actin
      regulatory proteins. On the other hand, a MMCPP blocking the activity of
      caldesmon reduced ET-1 promoted contraction pointing to a regulatory role of this
      protein and its activation pathway in HPASMC contraction. Inhibition of this
      MEK/ERK/p90RSK pathway, which is an upstream regulator of caldesmon
      phosphorylation, reduced ET-1 induced cell contraction. While the regulation of
      ET-1 induced cell contraction was found to be similar in PAH and non-PAH cells, a
      key difference was the response to pharmacological inhibitors and to siRNA
      knockdown of Rho kinases (ROCK1/ROCK2). The PAH cells required much higher
      concentrations of inhibitors to abrogate ET-1 induced contractions and their
      contraction was not affected by siRNA against either ROCK1 or ROCK2. Lastly,
      blocking of L-type and T-type Ca2+ channels had no effect on ET-1 or BK induced
      contraction. However, inhibiting the activity of the sarcoplasmic reticulum Ca2+
      ATPase blunted ET-1 and BK induced HPASMC contraction in both PAH and non-PAH
      derived HPASMC. In summary, our findings here together with previous
      communications illustrate similarities and differences in the regulation PAH and
      non-PAH smooth muscle cell contraction relating to calcium translocation,
      RhoA/ROCK signaling and the activity of caldesmon. These findings may provide
      useful tools in achieving the regulation of the vascular hypercontractility
      taking place in PAH.

PMID- 29649320
TI  - Strychnos pseudoquina modulates the morphological reorganization of the scar
      tissue of second intention cutaneous wounds in rats.
AB  - Natural substances are used in folk medicines to treat injuries. Strychnos
      pseudoquina has scarring, antipyretic, and antimalarial actions. The present
      study aimed to analyze the effect of S. pseudoquina on cutaneous wound healing in
      rats. The S. pseudoquina extract was submitted to phytochemical prospection. The
      levels of flavonoids and total phenolic compounds in the extract were 50.7 mg/g
      and 2.59 mg/g, respectively. Thirty Wistar rats were individualized in cages with
      food and water ad libitum (registration no. 730/2014). After anesthesia, three
      circular wounds (12mm diameter) were made in the animals, which were randomly
      separated into five treatments: Sal, saline; VO, ointment vehicles (lanolin and
      Vaseline); SS, positive control (silver sulfadiazine 1%); LE 5, freeze-dried
      extract 5%; and LE 10, lyophilized extract 10%. The animals were treated with the
      ointment daily for 21 days. Every seven days, the area and the rate of wound
      contraction were evaluated. Tissue samples were removed for histopathological
      analysis of the number of mast cells, elastic and collagen fibers, and
      biochemical analyses, quantification of malondialdehyde (MDA), carbonylated
      proteins (PCN), superoxide dismutase (SOD), catalase (CAT), transforming growth
      factor beta (TGF-beta), Interleukin 10 (IL-10) and tumor necrosis factor (TNF).
      The number of mast cells, collagen and elastic fibers in the rat wounds were
      higher in the treatments with the plant. The extract also stimulated the activity
      of antioxidant enzymes, particularly SOD, presenting high levels, and maintained
      low levels of PCN. The TGF-beta and IL-10 concentration was higher in the LE5 and
      LE10 treatment of the extract than in the Sal, OV and SS treatments on day 7. The
      ointment based on S. pseudoquina closed the wound faster and accelerated wound
      healing in animals.

PMID- 29649322
TI  - Correction: Aminoazo dye-protein-adduct enhances inhibitory effect on
      digestibility and damages to Gastro-Duodenal-Hepatic axis.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0170555.].

PMID- 29649321
TI  - Prediction of lateral pelvic lymph node metastasis in patients with locally
      advanced rectal cancer with preoperative chemoradiotherapy: Focus on MR imaging
      findings.
AB  - PURPOSE: To investigate the predictive factors for lateral pelvic lymph node
      (LPLN) metastasis in patients with locally advanced rectal cancer treated with
      preoperative chemoradiotherapy (CRT). MATERIALS AND METHODS: Fifty-seven patients
      with locally advanced rectal cancer and LPLNs larger than 5 mm underwent LPLN
      dissection (LPLD) after preoperative CRT. The MRI findings, including the
      apparent diffusion coefficient value and LPLN size reduction rate before/after
      CRT; clinical factors; and pathologic results were evaluated to identify the
      predictive factors associated with LPLN metastasis. RESULTS: LPLN metastasis was
      confirmed in 23 patients (40.4%). Metastasis was significantly higher in LPLNs
      with multiplicity, short-axis diameter >=8 mm before CRT, short-axis diameter >5
      mm after CRT, size reduction rate <=33.3%, heterogeneous signal intensity, and
      irregular margin (P<0.05) on MR. Multivariable analysis showed that pre-CRT short
      axis diameter of LPLNs >=8 mm, size reduction rate <=33.3%, and heterogeneous
      signal intensity were independently associated with LPLN metastasis. CONCLUSIONS:
      The size and signal intensity of LPLN before and after CRT are useful MRI
      findings to predict LPLN metastasis and are helpful to determine the indications
      for LPLD.

PMID- 29649323
TI  - Prognosis of cardiovascular and non-cardiovascular multimorbidity after acute
      coronary syndrome.
AB  - OBJECTIVE: To examine the prognosis of patients with cardiovascular and non
      cardiovascular multimorbidity after acute coronary syndrome compared to patients
      without prior multimorbidity. METHODS: This multicenter prospective cohort study
      in Switzerland included 5,635 patients hospitalized with acute coronary syndrome
      between 2009 and 2014, with a one-year follow-up period. We defined
      cardiovascular and non-cardiovascular multimorbidity as having at least two prior
      comorbidities before the index hospitalization. Multivariable adjusted Cox
      proportional models were built to assess the one-year risk of recurrent
      cardiovascular events, defined as cardiovascular mortality and non-fatal
      myocardial infarction or stroke. The final model was adjusted for age, gender,
      body mass index, tobacco consumption, education, and family history of
      cardiovascular disease, prescription of high-dose statinsat discharge and use of
      cardiac rehabilitation after discharge. RESULTS: Overall, 3,664 patients (65%)
      had no multimorbidity, 1,839 (33%) had cardiovascular multimorbidity, 62 (1%) had
      non-cardiovascular multimorbidity, and 70 (1%) had both cardiovascular and non
      cardiovascular multimorbidity. The multivariate risk of recurrent cardiovascular
      events was increased among patients with cardiovascular multimorbidity (hazard
      ratio (HR) 2.05, 95% CI: 1.54-2.73, p<0.001) and patients with non-cardiovascular
      multimorbidity (HR 2.57, 95% CI: 1.04-6.35, p = 0.04) compared to patients
      without multimorbidity. Patients with cardiovascular and non-cardiovascular
      multimorbidity had the highest risk of recurrence with a HR of 5.19, 95% CI: 2.79
      9.64, p<0.001, compared to patients without multimorbidity. CONCLUSIONS:
      Multimorbidity increased by two-fold the risk of cardiovascular events over the
      year after an acute coronary syndrome. The magnitude of this increased risk was
      similar for patients with cardiovascular or non-cardiovascular multimorbidity.

PMID- 29649325
TI  - Evaluation of porogen factors for the preparation of ion imprinted polymer
      monoliths used in mercury removal.
AB  - In the present study, ion imprinted polymer monoliths (IIPMs) were developed to
      overcome the limitations of ion imprinted polymer particles (IIPPs) used for the
      removal of Hg(II) ions from waste water samples. The adsorbents preparation,
      characterization and Hg(II) removal were very well reported. The IIPMs on porogen
      optimization was prepared using the molding technique with Hg(II) as a template
      ion, [2-(methacryloyloxy)ethyl]trimethylammonium cysteine (MAETC) as ligand,
      methacrylic acid (MAA) as functional monomer, ethylene glycol dimethacrylamide
      (EGDMA) as cross-linker, benzoyl peroxide as an initiator and methanol and
      acetonitrile as porogen in the polypropylene tube (drinking straw) as mold. The
      IIPMs prepared with higher volumes of porogen were indicated to have a good
      adsorption rate for the Hg(II) removal along with good water permeability and
      larger porosity as compared to a lower volume of porogen. The IIPMs prepared
      using the binary porogen were able to improve the porosity and surface area of
      the monolithic polymers as compared to the single porogen added IIPMs. Finally,
      we indicate from our analysis that the IIPM having the efficient capacity for the
      Hg(II) ions is easy to prepare, and has higher water permeability along with high
      porosity and high adsorption capacity and all these factors making it one of the
      suitable adsorbent for the successful removal of Hg(II) ions.

PMID- 29649326
TI  - Unbounded and revocable hierarchical identity-based encryption with adaptive
      security, decryption key exposure resistant, and short public parameters.
AB  - Revocation functionality and hierarchy key delegation are two necessary and
      crucial requirements to identity-based cryptosystems. Revocable hierarchical
      identity-based encryption (RHIBE) has attracted a lot of attention in recent
      years, many RHIBE schemes have been proposed but shown to be either insecure or
      bounded where they have to fix the maximum hierarchical depth of RHIBE at setup.
      In this paper, we propose a new unbounded RHIBE scheme with decryption key
      exposure resilience and with short public system parameters, and prove our RHIBE
      scheme to be adaptively secure. Our system model is scalable inherently to
      accommodate more levels of user adaptively with no adding workload or restarting
      the system. By carefully designing the hybrid games, we overcome the subtle
      obstacle in applying the dual system encryption methodology for the unbounded and
      revocable HIBE. To the best of our knowledge, this is the first construction of
      adaptively secure unbounded RHIBE scheme.

PMID- 29649324
TI  - A low dose lipid infusion is sufficient to induce insulin resistance and a pro
      inflammatory response in human subjects.
AB  - OBJECTIVE: The root cause behind the low-grade inflammatory state seen in insulin
      resistant (obesity and type 2 diabetes) states is unclear. Insulin resistant
      subjects have elevations in plasma free fatty acids (FFA), which are ligands for
      the pro-inflammatory toll-like receptor (TLR)4 pathway. We tested the hypothesis
      that an experimental elevation in plasma FFA (within physiological levels) in
      lean individuals would upregulate TLR4 and activate downstream pathways (e.g.,
      MAPK) in circulating monocytes. RESEARCH DESIGN AND METHODS: Twelve lean, normal
      glucose-tolerant subjects received a low dose (30 ml/h) 48 h lipid or saline
      infusion on two different occasions. Monocyte TLR4 protein level, MAPK
      phosphorylation, and expression of genes in the TLR pathway were determined
      before and after each infusion. RESULTS: The lipid infusion significantly
      increased monocyte TLR4 protein and phosphorylation of JNK and p38 MAPK. Lipid
      mediated increases in TLR4 and p38 phosphorylation directly correlated with
      reduced peripheral insulin sensitivity (M value). Lipid increased levels of
      multiple genes linked to inflammation, including several TLRs, CD180, MAP3K7, and
      CXCL10. Monocytes exposed in vivo to lipid infusion exhibited enhanced in vitro
      basal and LPS-stimulated IL-1beta secretion. CONCLUSIONS: In lean subjects, a
      small increase in plasma FFA (as seen in insulin resistant subjects) is
      sufficient to upregulate TLR4 and stimulate inflammatory pathways (MAPK) in
      monocytes. Moreover, lipids prime monocytes to endotoxin. We provide proof-of
      concept data in humans indicating that the low-grade inflammatory state
      characteristic of obesity and type 2 diabetes could be caused (at least
      partially) by pro-inflammatory monocytes activated by excess lipids present in
      these individuals.

PMID- 29649327
TI  - Evaluation of intraoperative touch imprint cytology on axillary sentinel lymph
      nodes in invasive breast carcinomas, a retrospective study of 1227 patients
      comparing sensitivity in the different tumor subtypes.
AB  - BACKGROUND: Intraoperative evaluation of the axillary sentinel lymph node (SLN)
      in patients with breast carcinoma reduces the need of re-operations in cases
      where an axillary completion lymph node dissection (CLND) is indicated. Different
      methods have been used to determine the SLN status intraoperatively, e.g. frozen
      section histology (FS) and touch imprint cytology (TIC). The sensitivity of
      intraoperative TIC examination on SLN is not consistent between different studies
      and varies according to different tumor histologic subtypes, tumor size and the
      age of the patient. The aim of this study was to describe the specificity and
      sensitivity of TIC and to compare TIC sensitivity in the different histological
      subtypes of breast carcinoma. METHODS: A retrospective review was performed of
      1227 consecutive clinically node negative breast cancer patients treated with
      sentinel lymph node biopsy (SLNB) with intraoperative TIC between the years 2003
      and 2008. The SLN was bisected and stained using the May-Grunwald-Giemsa method
      and immunocytochemically with the antibody MNF-116. RESULTS: The overall
      sensitivity of the TIC test was 68.6% and the specificity was 99.8%. There was no
      statistically significant difference between the detection of SLN metastases from
      ductal carcinoma versus lobular carcinoma. The sensitivity improved over the
      period of the study. CONCLUSION: TIC is highly specific with an acceptable
      overall sensitivity. The sensitivity increased under the period of the study and
      it was higher in cases with larger size of the primary tumor. There was no
      difference in TIC sensitivity between the different histological subtypes.

PMID- 29649328
TI  - Association between KIR-HLA combination and ulcerative colitis and Crohn's
      disease in a Japanese population.
AB  - Inflammatory bowel disease (IBD) consists of ulcerative colitis (UC) and Crohn's
      disease (CD). Natural killer cell responses play a crucial role in autoimmune
      disease through innate immunity, in which killer cell immunoglobulin-like
      receptors (KIRs) are closely involved. Although the genetic combination of KIRs
      with their specific HLA class I ligands has been associated with IBD in
      Caucasians, such KIR-HLA receptor-ligand combinations are not fully understood in
      the Japanese. We investigated 14 KIR genes along with HLA-Bw and -C ligands in 90
      patients with UC and 50 patients with CD and compared them with the
      characteristics of 325 healthy control subjects. The frequency of HLA-Bw4 was
      significantly increased in patients with UC (P = 1.3 * 10-6; odds ratio [OR] =
      3.39) and CD (P = 0.0065; OR = 2.32) versus controls. The UC group had a
      significantly higher frequency of KIR2DS3 (P = 0.024; OR = 1.94) and lower
      frequency of KIR2DS4 (P = 0.019; OR = 0.40) and KIR2DL1-HLA-C2 (P = 0.035; OR =
      0.47). The Tel-A/B haplotype was significantly decreased in UC patients (P =
      0.0056; OR = 0.49). The frequency of KIR3DL1-HLA-Bw4 was significantly higher in
      patients with UC (P = 4.3 * 10-6; OR = 3.12) and CD (P = 0.0067; OR = 2.30). In
      conclusion, HLA-Bw4 and KIR-HLA pairs may play an important role in the genetic
      susceptibility to IBD in the Japanese.

PMID- 29649330
TI  - Protein subnuclear localization based on a new effective representation and
      intelligent kernel linear discriminant analysis by dichotomous greedy genetic
      algorithm.
AB  - A wide variety of methods have been proposed in protein subnuclear localization
      to improve the prediction accuracy. However, one important trend of these means
      is to treat fusion representation by fusing multiple feature representations, of
      which, the fusion process takes a lot of time. In view of this, this paper
      novelly proposed a method by combining a new single feature representation and a
      new algorithm to obtain good recognition rate. Specifically, based on the
      position-specific scoring matrix (PSSM), we proposed a new expression,
      correlation position-specific scoring matrix (CoPSSM) as the protein feature
      representation. Based on the classic nonlinear dimension reduction algorithm,
      kernel linear discriminant analysis (KLDA), we added a new discriminant criterion
      and proposed a dichotomous greedy genetic algorithm (DGGA) to intelligently
      select its kernel bandwidth parameter. Two public datasets with Jackknife test
      and KNN classifier were used for the numerical experiments. The results showed
      that the overall success rate (OSR) with single representation CoPSSM is larger
      than that with many relevant representations. The OSR of the proposed method can
      reach as high as 87.444% and 90.3361% for these two datasets, respectively,
      outperforming many current methods. To show the generalization of the proposed
      algorithm, two extra standard datasets of protein subcellular were chosen to
      conduct the expending experiment, and the prediction accuracy by Jackknife test
      and Independent test is still considerable.

PMID- 29649329
TI  - Overview and outcome of Hodgkin's Lymphoma: Experience of a single developing
      country's oncology centre.
AB  - Hodgkin's Lymphoma (HL) reveals variable epidemiological and clinico-pathological
      features in different geographical locations. In this retrospective study, we
      aimed to assess the epidemiological and clinic-pathological features, and outcome
      of HL patients treated at one hemato-oncology centre in Erbil, northern Iraq.
      Medical records of 103 HL patients treated over more than six years were
      reviewed. Treatment outcome was evaluated by measuring the 5-year overall and
      progression-free survival rates. The median age of patients was 23 years,
      children up to 17 years constituted 31.1%, and male to female ratio was 1:1.05.
      The majority (96.1%) of patients presented with lymphadenopathy. Nodular
      sclerosis subtype was the mostly encountered histologic type (48.5%); about half
      of the patients (49.5%) had stage II disease. Relapse occurred in 20 patients;
      the 5-year overall survival for children was better (89%) compared to adult
      patients (79%). The associated risk features found to have adverse effects on the
      survival, however, only high LDH level and presence of B-symptoms at presentation
      showed significant correlation. The epidemiological and clinical characteristics
      of HL in our locality followed the pattern in the western world. The 5-year
      overall and progression-free survivals were far below the international rates, a
      matter which may necessitate a revision to HL treatment strategy at our centre.

PMID- 29649331
TI  - Ecological succession of adult necrophilous insects on neonate Sus scrofa
      domesticus in central North Carolina.
AB  - The necrophilous insect fauna on carcasses varies seasonally and geographically.
      The ecological succession of insects arriving to decaying neonate pig carcasses
      in central North Carolina during late summer was sampled using a novel vented
      chamber collection method. We collected six blow fly species, flesh flies, house
      flies and 10 beetle taxa, including four species of scarab beetles. Necrophilous
      fly activity dominated the early decomposition stages, whereas beetle numbers
      remained low until day 4. By day 7, more than 50% of the pig carcasses were
      skeletonized and they attracted few insects. Differences in the taxa and
      successional patterns documented in this experiment and a previous study in the
      same location highlight the ecological variation in such investigations, and
      underscore the need for standardization, as well as for ecological succession
      studies on finer geographic scales.

PMID- 29649332
TI  - Development of novel EST-SSR markers for ploidy identification based on de novo
      transcriptome assembly for Misgurnus anguillicaudatus.
AB  - The co-existence of several ploidy types in natural populations makes the
      cyprinid loach Misgurnus anguillicaudatus an exciting model system to study the
      genetic and phenotypic consequences of ploidy variations. A first step in such
      effort is to identify the specific ploidy of an individual. Currently popular
      methods of karyotyping via cytological preparation or flow cytometry require a
      large amount of tissue (such as blood) samples, which can be damaging or fatal to
      the fishes. Here, we developed novel microsatellite markers (SSR markers) from M.
      anguillicaudatus and show that they can effectively discriminate ploidy using
      samples collected in a minimally invasive way. Specifically, we generated whole
      genome transcriptomes from multiple M. anguillicaudatus using the Illumina paired
      end sequencing. Approximately 150 million raw reads were assembled into 76,544
      non-redundant unigenes. A total of 8,194 potential SSR markers were identified.
      We selected 98 pairs with more than five tandem repeats for further assays. Out
      of 45 putative EST-SSR markers that successfully amplified and harbored
      polymorphism in diploids, 11 markers displayed high variability in tetraploids.
      We further demonstrate that a set of five EST-SSR markers selected from these are
      sufficient to distinguish ploidy levels, by first validating them on 69 reference
      specimens with known ploidy levels and then subsequently using fresh-collected 96
      ploidy-unknown specimens. The results from EST-SSR markers are highly concordant
      with those from independent flow cytometry analysis. The novel EST-SSR markers
      developed here should facilitate genetic studies of polyploidy in the emerging
      model system M. anguillicaudatus.

PMID- 29649333
TI  - Soluble T-cell receptor design influences functional yield in an E. coli
      chaperone-assisted expression system.
AB  - There is a quest for production of soluble protein of high quality for the study
      of T-cell receptors (TCRs), but expression often results in low yields of
      functional molecules. In this study, we used an E. coli chaperone-assisted
      periplasmic production system and compared expression of 4 different soluble TCR
      formats: single-chain TCR (scTCR), two different disulfide-linked TCR (dsTCR)
      formats, and chimeric Fab (cFab). A stabilized version of scTCR was also
      included. Additionally, we evaluated the influence of host (XL1-Blue or
      RosettaBlueTM) and the effect of IPTG induction on expression profiles. A celiac
      disease patient-derived TCR with specificity for gluten was used, and we achieved
      detectable expression for all formats and variants. We found that expression in
      RosettaBlueTM without IPTG induction resulted in the highest periplasmic yields.
      Moreover, after large-scale expression and protein purification, only the scTCR
      format was obtained in high yields. Importantly, stability engineering of the
      scTCR was a prerequisite for obtaining reliable biophysical characterization of
      the TCR-pMHC interaction. The scTCR format is readily compatible with high
      throughput screening approaches that may enable both development of reagents
      allowing for defined peptide MHC (pMHC) characterization and discovery of
      potential novel therapeutic leads.

PMID- 29649334
TI  - Urinary cGMP predicts major adverse renal events in patients with mild renal
      impairment and/or diabetes mellitus before exposure to contrast medium.
AB  - BACKGROUND: The use of iodine-based contrast agents entails the risk of contrast
      induced nephropathy (CIN). Radiocontrast agents elicit the third most common
      cause of nephropathy among hospitalized patients, accounting for 11-12% of cases.
      CIN is connected with clinically significant consequences, including increased
      morbidity, prolonged hospitalization, increased risk of complications, potential
      need for dialysis, and increased mortality rate. The number of in-hospital
      examinations using iodine-based contrast media has been significantly increasing
      over the last decade. In order to protect patients from possible complications of
      such examinations, new biomarkers are needed that are able to predict a risk of
      contrast-induced nephropathy. Urinary and plasma cyclic guanosine monophosphate
      (cGMP) concentrations are influenced by renal function. Urinary cGMP is primarily
      of renal cellular origin. Therefore, we assessed if urinary cGMP concentration
      may predict major adverse renal events (MARE) after contrast media exposure
      during coronary angiography. METHODS: Urine samples were prospectively collected
      from non-randomized consecutive patients with either diabetes or preexisting
      impaired kidney function receiving intra-arterial contrast medium (CM) for
      emergent or elective coronary angiography at the Charite Campus Mitte, University
      Hospital Berlin. Urinary cGMP concentration in spot urine was analyzed 24 hours
      after CM exposure. Patients were followed up over 90 days for occurrence of
      death, initiation of dialysis, doubling of plasma creatinine concentration or
      MARE. RESULTS: In total, 289 consecutive patients were included into the study.
      Urine cGMP/creatinine ratio 24 hours before CM exposure expressed as mean+/-SD
      was predictive for the need of dialysis (no dialysis: 89.77+/-92.85 MUM/mM, n =
      277; need for dialysis: 140.3+/-82.90 MUM/mM, n = 12, p = 0.008), death (no death
      during follow-up: 90.60+/-92.50 MUM/mM, n = 280; death during follow-up: 169.88+/
      81.52 MUM/mM, n = 9; p = 0.002), and the composite endpoint MARE (no MARE:
      86.02+/-93.17 MUM/mM, n = 271; MARE: 146.64+/-74.68 MUM/mM, n = 18, p<0.001)
      during the follow-up of 90 days after contrast media application. cGMP/creatinine
      ratio stayed significantly increased at values exceeding 120 MUM/mM in patients
      who developed MARE, required dialysis or died. CONCLUSIONS: Urinary
      cGMP/creatinine ratio >= 120 MUM/mM before CM exposure is a promising biomarker
      for the need of dialysis and all-cause mortality 90 days after CM exposure in
      patients with preexisting renal impairment or diabetes.

PMID- 29649335
TI  - Molecular characterization of the lipophorin receptor in the crustacean
      ectoparasite Lepeophtheirus salmonis.
AB  - The Salmon louse (Lepeophtheirus salmonis) is a marine ectoparasite of salmonid
      fish in the Northern Hemisphere and considered as a major challenge in
      aquaculture and a threat to wild populations of salmonids. Adult female lice
      produce a large number of lipid-rich eggs, however, the mechanism of maternal
      lipid transport into developing eggs during salmon louse reproduction has not
      been described. In the present study, a full-length L. salmonis lipophorin
      receptor (LsLpR) consisting of 16 exons was obtained by RACE and RT-PCR. The
      predicted ORF was 952 amino acids and structural analysis showed five functional
      domains that are similar to LpR of insects and decapods. Phylogenetic analysis
      placed the LsLpR together with LpRs from decapods and insects. Expression
      analysis revealed that the relative abundance of LsLpR transcripts was highest in
      the larvae and adult female lice. In adult females, the LsLpR transcripts and
      protein were found in the ovary and vitellogenic oocytes whereas, in larvae, the
      LsLpR transcripts were found in the neuronal somata of the brain and the
      intestine. Oil Red O stain results revealed that storage of neutral lipids was
      found in vitellogenic oocytes and ovaries of adult females, and in the yolk of
      larvae. Moreover, RNA interference (RNAi) was conducted to demonstrate the
      function of LsLpR in reproduction and lipid metabolism in L. salmonis. In larvae,
      the transcription of LsLpR was decreased by 44-54% while in an experiment LsLpR
      knockdown female lice produced 72% less offspring than control lice.

PMID- 29649338
TI  - Guilt leads to enhanced facing-the-viewer bias.
AB  - As an important moral emotion, guilt plays a critical role in social interaction.
      It has been found that people tended to exhibit prosocial behavior under
      circumstances of guilt. However, all extant studies have predominantly focused on
      the influence of guilt on macro-level behavior. So far, no study has investigated
      whether guilt affects people's micro-level perception. The current study closes
      this gap by examining whether guilt affects one's inclination to perceive
      approaching motion. We achieved this aim by probing a facing-the-viewer bias (FTV
      bias). Specifically, when an ambiguous walking biological motion display is
      presented to participants via the point-light display technique, participants
      tend to perceive a walking agent approaching them. We hypothesized that guilt
      modulated FTV bias. To test this hypothesis, we adopted a two-person situation
      induction task to induce guilt, whereby participants were induced to feel that
      because of their poor task performance, their partner did not receive a
      satisfactory payment. We found that when participants were told that the
      perceived biological motion was motion-captured from their partner, the FTV bias
      was significantly increased for guilty participants relative to neutral
      participants. However, when participants were informed that the perceived
      biological motion was from a third neutral agent, the FTV bias was not modulated
      by guilt. These results suggest that guilt influences one's inclination to
      perceive approaching motion, but this effect is constrained to the person towards
      whom guilt is directed.

PMID- 29649336
TI  - Molecular mechanisms of fission in echinoderms: Transcriptome analysis.
AB  - Echinoderms are capable of asexual reproduction by fission. An individual divides
      into parts due to changes in the strength of connective tissue of the body wall.
      The structure of connective tissue and the mechanisms of variations in its
      strength in echinoderms remain poorly studied. An analysis of transcriptomes of
      individuals during the process of fission provides a new opportunity to
      understand the mechanisms of connective tissue mutability. In the holothurian
      Cladolabes schmeltzii, we have found a rather complex organization of connective
      tissue. Transcripts of genes encoding a wide range of structural proteins of
      extracellular matrix, as well as various proteases and their inhibitors, have
      been discovered. All these molecules may constitute a part of the mechanism of
      connective tissue mutability. According to our data, the extracellular matrix of
      echinoderms is substantially distinguished from that of vertebrates by the lack
      of elastin, fibronectins, and tenascins. In case of fission, a large number of
      genes of transcription factors and components of different signaling pathways are
      expressed. Products of these genes are probably involved in regulation of asexual
      reproduction, connective tissue mutability, and preparation of tissues for
      subsequent regeneration. It has been shown that holothurian tensilins are a
      special group of tissue inhibitors of metalloproteinases, which has formed within
      the class Holothuroidea and is absent from other echinoderms. Our data can serve
      a basis for the further study of the mechanisms of extracellular matrix
      mutability, as well as the mechanisms responsible for asexual reproduction in
      echinoderms.

PMID- 29649337
TI  - Leg length, skull circumference, and the incidence of dementia in Latin America
      and China: A 10/66 population-based cohort study.
AB  - BACKGROUND: Adult leg length is influenced by nutrition in the first few years of
      life. Adult head circumference is an indicator of brain growth. Cross-sectional
      studies indicate inverse associations with dementia risk, but there have been few
      prospective studies. METHODS: Population-based cohort studies in urban sites in
      Cuba, Dominican Republic Puerto Rico and Venezuela, and rural and urban sites in
      Peru, Mexico and China. Sociodemographic and risk factor questionnaires were
      administered to all participants, and anthropometric measures taken, with
      ascertainment of incident dementia, and mortality, three to five years later.
      RESULTS: Of the original at risk cohort of 13,587 persons aged 65 years and over,
      2,443 (18.0%) were lost to follow-up; 10,540 persons with skull circumference
      assessments were followed up for 40,466 person years, and 10,400 with leg length
      assessments were followed up for 39,954 person years. There were 1,009 cases of
      incident dementia, and 1,605 dementia free deaths. The fixed effect pooled meta
      analysed adjusted subhazard ratio (ASHR) for leg length (highest vs. lowest
      quarter) was 0.80 (95% CI, 0.66-0.97) and for skull circumference was 1.02 (95%
      CI, 0.84-1.25), with no heterogeneity of effect between sites (I2 = 0%). Leg
      length measurements tended to be shorter at follow-up, particularly for those
      with baseline cognitive impairment and dementia. However, leg length change was
      not associated with dementia incidence (ASHR, per cm 1.006, 95% CI 0.992-1.020),
      and the effect of leg length was little altered after adjusting for baseline
      frailty (ASHR 0.82, 95% CI 0.67-0.99). A priori hypotheses regarding effect
      modification by gender or educational level were not supported. However, the
      effect of skull circumference was modified by gender (M vs F ASHR 0.86, 95% CI
      0.75-0.98), but in the opposite direction to that hypothesized with a greater
      protective effect of larger skull dimensions in men. CONCLUSIONS: Consistent
      findings across settings provide quite strong support for an association between
      adult leg length and dementia incidence in late-life. Leg length is a relatively
      stable marker of early life nutritional programming, which may confer brain
      reserve and protect against neurodegeneration in later life through mitigation of
      cardiometabolic risk. Further clarification of these associations could inform
      predictive models for future dementia incidence in the context of secular trends
      in adult height, and invigorate global efforts to improve childhood nutrition,
      growth and development.

PMID- 29649340
TI  - The relationship between alkaline phosphatase and bone alkaline phosphatase
      activity and the growth hormone/insulin-like growth factor-1 axis and vitamin D
      status in children with growth hormone deficiency.
AB  - The relationships between bone turnover, the growth hormone/insulin-like growth
      factor-1 (GH/IGF-1) axis and vitamin D are complex, but still not fully
      explained. The GH/IGF-1 axis and vitamin D can mutually modulate each other's
      metabolism and influence the activation of cell proliferation, maturation, and
      mineralization as well as bone resorption. The aim of this study was to evaluate
      the reciprocal associations between bone formation markers [alkaline phosphatase
      (ALP), bone alkaline phosphatase (BALP)], the GH/IGF-1 axis and 25-hydroxyvitamin
      D [25(OH)D] in children with growth hormone deficiency at baseline and during
      recombinant human growth hormone (rhGH) therapy. ALP, BALP, 25(OH)D and IGF-1
      levels were evaluated in 53 patients included in this prospective three-year
      study. ALP, BALP and IGF-1 increased during rhGH therapy. Baseline ALP activity
      correlated positively with baseline height velocity (HV). ALP and BALP activity
      at 12 months correlated positively with HV in the first year of therapy. We found
      positive correlations between ALP and IGF-1 at baseline and during the first year
      of therapy, between BALP activity at 12 months and rhGH dose in the first year of
      therapy, and between doses of cholecalciferol in the first year of rhGH therapy
      and early changes in BALP activity during rhGH therapy. Our results indicate that
      vitamin D supplementation enhances the effect of rhGH on bone formation process,
      which could improve the effects of rhGH therapy. ALP and BALP activity are useful
      in the early prediction of the effects of rhGH therapy, but their utility as long
      term predictors seemed insufficient.

PMID- 29649341
TI  - How Does Your PICCOMPARE? A Pilot Randomized Controlled Trial Comparing Various
      PICC Materials in Pediatrics.
AB  - BACKGROUND: Despite the popularity of peripherally inserted central catheters
      (PICCs), recent literature highlights their potential injurious complications.
      Innovative PICC materials have been developed to prevent thrombosis and infection
      formation (Endexo(r)) and antireflux valves to prevent occlusion (pressure
      activated safety valve(r)). No large randomized controlled trial has assessed
      these technologies. Our primary aim was to evaluate the feasibility of a large
      randomized controlled efficacy trial of PICC materials and design to reduce PICC
      complication in pediatrics. METHODS: A randomized controlled feasibility trial
      was undertaken at the Lady Cilento Children's Hospital in South Brisbane,
      Australia, between March 2016 and November 2016. Consecutive recruitment of 150
      pediatric participants were randomly assigned to receive either (1) polyurethane
      PICC with a clamp or (2) BioFlo(r) PICC (AngioDynamics Inc, Queensbury, NY).
      Primary outcomes were trial feasibility, including PICC failure (thrombosis,
      occlusion, infection, breakage, or dislodgement). Secondary outcomes were PICC
      complications during use. RESULTS: Protocol feasibility was established,
      including staff and patient acceptability, timely recruitment, no missing primary
      outcome data, and 0% attrition. PICC failure was 22% (16 of 74, standard care)
      and 11% (8 of 72, BioFlo(r)) corresponding to 12.6 and 7.3 failures per 1000
      hours (risk ratio 0.58; 95% confidence interval, 0.21-1.43; P = .172). PICC
      failures were primarily due to thrombosis (standard care 7% versus BioFlo(r) 3%)
      and complete occlusion (standard care 7% versus BioFlo(r) 1%). No blood stream
      infections occurred. Significantly fewer patients with BioFlo(r) had PICC
      complications during use (15% vs 34%; P = .009). CONCLUSIONS: BioFlo(r) PICCs
      appear potentially safer for pediatrics than traditional standard care PICCs with
      a clamp. Further research is required to definitively identify clinical, cost
      effective methods to prevent PICC failure and improve reliability.

PMID- 29649339
TI  - Pathogenic factors associated with development of disseminated intravascular
      coagulopathy (DIC) in a tertiary academic hospital in South Africa.
AB  - INTRODUCTION: Disseminated intravascular coagulopathy (DIC) is a thrombotic
      microangiopathy arising from consumption of both coagulation factors and
      platelets. DIC is triggered by a number of clinical conditions including severe
      infection, trauma and obstetric complications. Early diagnosis and treatment of
      the underlying condition is paramount. A high clinical index of suspicion is
      needed to ensure that patients at risk of developing DIC are appropriately
      investigated. METHODS: In order to establish the clinical conditions most
      frequently associated with DIC, we reviewed all DIC screens received at a
      tertiary hospital in Johannesburg, South Africa over a 1 year period. RESULTS:
      The commonest clinical condition associated with DIC in our population was
      infection with 84% of patients infected with an identified pathogen. The most
      frequently diagnosed pathogen was HIV followed by Mycobacterium tuberculosis and
      other bacterial infections. In the majority of cases, bacteria were isolated from
      blood cultures. In 47 patients, HIV was the only pathogen which could be
      isolated. A relative risk ratio of 2.73 and an odds ratio of 29.97 was attributed
      to HIV for development of a DIC. A malignancy was present in 51 of the patients
      of which approximately 60% had co-existing infection. No cause could be
      attributed in 30 patients. CONCLUSION: Infection was identified in the majority
      of the patients diagnosed with DIC in this study. HIV showed the highest relative
      risk ratio of all pathogens although previous studies have not suggested that HIV
      was strongly associated with DIC. In almost half of the HIV infected patients,
      there was no other pathogen isolated despite extensive investigation. This
      suggests that HIV has a strong association with the development of DIC,
      warranting further research into the relationship between HIV and disseminated
      microvascular thrombosis.

PMID- 29649342
TI  - A homogeneous electrochemical sensor for Hg2+ determination in environmental
      water based on the T-Hg2+-T structure and exonuclease III-assisted recycling
      amplification.
AB  - A simple, fast, sensitive, and homogeneous electrochemical sensor based on the T
      Hg2+-T structure and exonuclease III-assisted recycling amplification has been
      constructed for mercury ion (Hg2+) detection. The cT and methylene blue-labeled
      DNA probes (MB-TDNA) were designed to contain poly T sequences, which were
      repulsed from the negatively charged indium tin oxide (ITO) electrode due to
      their abundant negative charges. Hg2+ could trigger the formation of double
      stranded DNA (dsDNA) between two DNA probes owing to the stable T-Hg2+-T
      structure. Then, Exo III specifically recognizes the cleavage of the double
      stranded structure to release a methylene blue-labeled mononucleotide fragment
      (MB-MF). Moreover, the release of the target Hg2+ induces new hybridization and
      produces a large number of MB-MFs; MB-MFs are not repulsed by the negatively
      charged ITO electrode surface, thus producing a significant current signal. Under
      optimal conditions, the differential pulse voltammetric (DPV) response had a
      linear relationship with the logarithm of Hg2+ concentration in the range of 1.0
      nM-0.5 MUM, and the proposed method displayed great applicability for detecting
      Hg2+ in tap-water samples.

PMID- 29649343
TI  - Autophoretic motion in three dimensions.
AB  - Janus particles with the ability to move phoretically in self-generated chemical
      concentration gradients are model systems for active matter. Their motion
      typically consists of straight paths with rotational diffusion being the dominant
      reorientation mechanism. In this paper, we show theoretically that by a suitable
      surface coverage of both activity and mobility, translational and rotational
      motion can be induced arbitrarily in three dimensions. The resulting trajectories
      are in general helical, and their pitch and radius can be controlled by adjusting
      the angle between the translational and angular velocity. Building on the
      classical mathematical framework for axisymmetric self-phoretic motion under
      fixed-flux chemical boundary conditions, we first show how to calculate the most
      general three-dimensional motion for an arbitrary surface coverage of a spherical
      particle. After illustrating our results on surface distributions, we next
      introduce a simple intuitive patch model to serve as a guide for designing
      arbitrary phoretic spheres.

PMID- 29649344
TI  - The transformation behaviour of "alucones", deposited by molecular layer
      deposition, in nanoporous Al2O3 layers.
AB  - Nanoporous alumina films can be synthesized from hybrid organic-inorganic
      "alucone" films deposited by molecular layer deposition (MLD) by wet etching in
      deionized water or calcination in air at 500  degrees C. This transformation
      process was systematically investigated for two alucone chemistries based on
      ethylene glycol (EG) and glycerol (GL). Ellipsometric porosimetry (EP) was used
      for the characterization of the porous alumina structures that are formed as a
      result of the treatments. Etching in deionized water transforms both EG- and GL
      alucones into porous alumina with a porosity of about 40%, albeit with a
      different pore structure: cylindrical pores for EG-alucones and ink-bottle
      structures for GL-alucones. Calcination in air up to 500  degrees C only
      successfully transformed EG-alucones into porous alumina if the chosen heating
      and cooling rate was lower than 200  degrees C h-1. Below this ramp rate, a
      relationship between the resulting porosity and the ramp rate was found. At the
      lowest investigated ramp rate of 20  degrees C h-1, the highest porosity of 36%
      was achieved. For this treatment type, the pore shape was of the ink-bottle type
      for all investigated ramp rates with narrow 1 nm-sized pores. Infrared
      spectroscopy (FTIR) and X-ray photoelectron spectroscopy revealed that the final
      chemistry of the porous structures was slightly different for both treatments due
      to trace amounts of carbon left behind by water etching. This suggests that the
      internal surface of the porous structure has a different termination depending on
      the chosen treatment. The precise thickness control and conformal nature inherent
      to MLD combined with the wet and heat treatments enables the coating of complex
      3D structures with a porous alumina film with a well-defined thickness and pore
      structure.

PMID- 29649345
TI  - Enhanced singlet oxygen generation of a soft salt through efficient energy
      transfer between two ionic metal complexes.
AB  - In this study, a soft salt complex based photosensitizer has been developed for
      photodynamic therapy (PDT) of cancer cells. The iridium(iii) complex
      [Ir(L)(L')]3+(PF6-)3 (C1) with L and L' being terpyridine ligands (L = 4'-phenyl
      2,2':6',2''-terpyridine, L' = 3-([2,2':6',2''-terpyridin]-4'-yl)-9-hexyl-9H
      carbazole) was chosen as the cationic component, and the iridium(iii) complex
      [Ir(dfppy)2CN2]-Bu4N+ (A1) was selected as the anionic component. Complexes C1
      and A1 are directly connected through electrostatic interaction to form a soft
      salt based photosensitizer (S1), which exhibited an enhanced singlet oxygen
      generation rate because of efficient energy transfer between two ionic metal
      complexes. Furthermore, this novel photosensitizer was successfully applied in
      photodynamic therapy (PDT) of cancer cells for the first time.

PMID- 29649346
TI  - Decaborane anion tautomerism: ion pairing and proton transfer control.
AB  - The reaction of 1,8-bis(dimethylamino)naphthalene-which is often referred by the
      trade name Proton-Sponge (PS)-with decaborane in hexane afforded [HPS][B10H13]
      (1) salt as a pale-yellow precipitate. Variable-temperature NMR studies allowed
      the full assignment of 1H and 11B spectra for this familiar ten-vertex polyhedral
      anion. In addition, this work reveals that an increase in the temperature leads
      to the intramolecular exchange of three B-H-B hydrogen atoms around the hexagonal
      face of the boat-shaped cluster. This previously unrecognised H-tautomerism
      complements the long-known low-energy proton exchange of only one of the bridging
      hydrogen atoms. The temperature dependent proton fluxional behaviour controls the
      molecular environment of the polyhedral cage, averaging the negative charge of
      the anion. The result is a debilitation of the cation-anion interactions in
      solution, favouring the transfer of the proton from the organic aromatic cation,
      [HPS]+, to the polyhedral anion, [B10H13]-. This proton transfer affords Proton
      Sponge and decaborane, increasing the entropy of the system and sustaining an
      equilibrium which at high temperatures shifts toward the neutral reactants and at
      low temperatures moves toward the ionic products. A single X-ray diffraction
      analysis of 1 is discussed.

PMID- 29649347
TI  - Two photochromic iodoargentate hybrids with adjustable photoresponsive mechanism.
AB  - Two organic-inorganic iodoargentate hybrids, [(HPBI).(MeCN)][Ag3I4] (1) and
      [MPBI][Ag3I4] (2) (HPBI+ = 1-proton-2-phenylbenzimidazolium, MPBI+ = 1,3-dimethyl
      2-phenylbenzimidazolium), have been synthesized. They exhibit structure-dependent
      photochromism with fast response and wide color range (from colorless to purple
      and dark green in 1 and 2, respectively), which are attributed to a substantially
      reversible photolysis for 1 and dual photolysis and photoinduced secondary ET for
      2.

PMID- 29649348
TI  - Development of the American College of Rheumatology Electronic Clinical Quality
      Measures for Gout.
AB  - OBJECTIVE: Electronic clinical quality measures (eCQMs) are increasingly used by
      health registries and third parties to evaluate and improve the quality of health
      care. To complete these eCQMs, data are extracted from electronic health records
      (EHRs). The treatment of gout has been an area identified with gaps in quality of
      care. On behalf of the American College of Rheumatology (ACR), we sought to
      develop and test eCQMs to evaluate gout care. METHODS: Drawing from the 2012 ACR
      gout guidelines, a working group developed candidate gout process measures that
      were evaluated by an interdisciplinary panel of health care stakeholders, the ACR
      Quality Measures Subcommittee (QMS), and ultimately the ACR Board of Directors
      for formal validity testing. For each of the selected gout eCQMs, 3 clinical
      sites using different EHR systems tested the scientific feasibility and validity
      of the measures. Measures appropriate for accountability were presented for
      national endorsement. RESULTS: Of the 10 proposed eCQMs, 4 were endorsed by the
      ACR QMS, 3 were incorporated into the ACR's Rheumatology Informatics System for
      Effectiveness (RISE) Registry, and 2 were endorsed by the National Quality Forum.
      The 3 eCQMs incorporated into RISE (evaluating indications for urate-lowering
      therapy [ULT]), monitoring serum urate, and treat-to-target outcome) demonstrated
      high validity and reliability. Proportions of patients passing these 3 eCQMs in
      RISE and at the 3 clinical testing sites ranged between 32% and 58%, indicating
      significant room for improvement in care. CONCLUSION: Three eCQMs have been
      validated and implemented into RISE. Two of these measures (evaluating
      indications for ULT and monitoring serum urate) are available for use in federal
      quality reporting programs. Performance on these measures suggests there is
      significant room for improvement in the management of gout.

PMID- 29649349
TI  - Differential Scavenging Among Pig, Rabbit, and Human Subjects.
AB  - Different animal species have been used as proxies for human remains in
      decomposition studies for decades, although few studies have sought to validate
      their use in research aimed at estimating the postmortem interval. This study
      examines 45 pig, rabbit, and human subjects placed in three seasonal trials at
      the Anthropology Research Facility. In an earlier paper, we found that overall
      decomposition trends did vary between species that could be due to differential
      insect and scavenger behavior. This study specifically examines if scavenger
      behavior differs by carrion species. Daily photographs, game camera photographs,
      written observations, and Total Body Score (TBS) documented scavenging and
      decomposition changes. Results show that raccoons were the most commonly observed
      vertebrate scavenger, that scavenging was most extensive in winter, and that
      certain human subjects were preferred over other humans and all non-human
      subjects. Finally, scavenging activity greatly reduces the accuracy of postmortem
      interval estimates based on TBS.

PMID- 29649350
TI  - Evaluation of DNA Extraction Methods from Waterlogged Bones: A Pilot Study.
AB  - When deaths occur in water, soft tissue decomposes after a temperature-dependent
      period, making DNA identification dependent on bone. This study examined the
      effects of water on bone DNA purity and quantity, and determined the best of
      three extraction methods for isolating DNA. The organic phenol-chloroform method
      consistently extracted DNA approximating the accepted 260/280 purity value
      (~1.8); ChargeSwitch(r) gDNA Plant Kit and DNeasy Blood and Tissue Kit produced
      fair and unacceptable values, respectively. The purity value for humerus and rib
      samples was consistent across accumulated degree days (ADD). Significant
      differences in quantification among extraction methods and between bone types
      were identified. Ribs and ChargeSwitch(r) gDNA Plant Kit samples produced the
      lowest mean Ct values of the bone types and the extraction methods, respectively.
      Therefore, this study proposes that magnetic bead technology extraction methods
      and ribs be considered when processing bones that have been submerged in water
      for any length of time.

PMID- 29649351
TI  - Epidemiological Study of Carbon Monoxide Deaths in Scotland 2007-2016.
AB  - Carbon monoxide (CO) intoxications are quite frequent in forensic toxicology.
      Using a sample of 209 CO-positive deaths in Scotland from 2007 to 2016, this
      study provides ranges of percentage CO saturations (%COHb) according to the CO
      source and examines any correlation with age, gender, alcohol, and preexisting
      disease. It also reports the full toxicological findings, including drug
      concentrations, in CO-positive cases. The highest numbers of fatalities involved
      males, occurred during autumn/winter, and the main source of CO was fire. The
      median %COHb in fire-related cases was significantly lower than in non-fire
      related cases such as those involving exhausts, generators and gas supply
      systems, and portable BBQs. There was no relationship between %COHb and age,
      blood alcohol concentration, or the presence of preexisting cardiovascular and/or
      respiratory disease. Toxicology results revealed that prescription medications
      were the most commonly detected drug group and that the number of cases positive
      for controlled drugs was small.

PMID- 29649353
TI  - The Microbiota, Cancer and the "Human Superorganism".

PMID- 29649352
TI  - Interstitial Lung Diseases in the U.S. Mining Industry: Using MSHA Data to
      Examine Trends and the Prevention Effects of Compliance with Health Regulations,
      1996-2015.
AB  - Given the recent increase in dust-induced lung disease among U.S. coal miners and
      the respiratory hazards encountered across the U.S. mining industry, it is
      important to enhance an understanding of lung disease trends and the
      organizational contexts that precede these events. In addition to exploring
      overall trends reported to the Mine Safety and Health Administration (MSHA), the
      current study uses MSHA's enforcement database to examine whether or not
      compliance with health regulations resulted in fewer mine-level counts of these
      diseases over time. The findings suggest that interstitial lung diseases were
      more prevalent in coal mines compared to other mining commodities, in Appalachian
      coal mines compared to the rest of the United States, and in underground compared
      to surface coal mines. Mines that followed a relevant subset of MSHA's health
      regulations were less likely to report a lung disease over time. The findings are
      discussed from a lung disease prevention strategy perspective.

PMID- 29649354
TI  - CPR Blitzkrieg: Training 500 High School Students in less than 48 hours.
AB  - BACKGROUND Many states, including Arkansas, require CPR training before high
      school graduation. METHODS We modified the American Heart Association's CPR in
      Schools curriculum to deliver CPR and AED training with maximal individual
      practice. RESULTS 520 students were trained over a two-day period at Little Rock
      Central High School. Three students were unable to effectively participate due to
      physical limitations. The model was later applied at the five other district
      public high schools. CONCLUSIONS Training large numbers of students in a time
      compressed formal is feasible with a highly dedicated, practiced instructor team.
      This model may be applicable to workplace settings.

PMID- 29649355
TI  - Emergency Department Assessment and Treatment for Medicaid Patients.

PMID- 29649356
TI  - Acute Renal Infarction - Presentation and Causes: Two Case Reports.

PMID- 29649357
TI  - Amiodarone Induced Interstitial and Organizing Pneumonia Reversed with Steroids.
AB  - Amiodarone is a widely used antiarrhythmic agent for supraventricular and
      ventricular tachyarrhythmias. It is known to cause pulmonary toxicity, which can
      manifest in a variety of presentations, ranging from asymptomatic to fatal. We
      present a case of chronic interstitial pneumonia with organizing pneumonia
      induced by amiodarone that was successfully treated with drug cessation and use
      of corticosteroids. The patient experienced complete resolution of symptoms and
      full recovery of lung function after the course of steroids.

PMID- 29649358
TI  - Constrained Adherable Area of Nanotopographic Surfaces Promotes Cell Migration
      through the Regulation of Focal Adhesion via Focal Adhesion Kinase/Rac1
      Activation.
AB  - Cell migration is crucial in physiological and pathological processes such as
      embryonic development and wound healing; such migration is strongly guided by the
      surrounding nanostructured extracellular matrix. Previous studies have
      extensively studied the cell migration on anisotropic nanotopographic surfaces;
      however, only a few studies have reported cell migration on isotropic
      nanotopographic surfaces. We herein, for the first time, propose a novel concept
      of adherable area on cell migration using isotropic nanopore surfaces with
      sufficient nanopore depth by adopting a high aspect ratio. As the pore size of
      the nanopore surface was controlled to 200, 300, and 400 nm in a fixed center-to
      center distance of 480 nm, it produced 86, 68, and 36% of adherable area,
      respectively, on the fabricated surface. A meticulous investigation of the cell
      migration in response to changes in the constrained adherable area of the
      nanotopographic surface showed 1.4-, 1.5-, and 1.6-fold increase in migration
      speeds and a 1.4-, 2-, and 2.5-fold decrease in the number of focal adhesions as
      the adherable area was decreased to 86, 68, and 36%, respectively. Furthermore, a
      strong activation of FAK/Rac1 signaling was observed to be involved in the
      promoted cell migration. These results suggest that the reduced adherable area
      promotes cell migration through decreasing the FA formation, which in turn
      upregulates FAK/Rac1 activation. The findings in this study can be utilized to
      control the cell migration behaviors, which is a powerful tool in the research
      fields involving cell migration such as promoting wound healing and tissue
      repair.

PMID- 29649359
TI  - Base-Promoted Synthesis of 2-Aryl Quinazolines from 2-Aminobenzylamines in Water.
AB  - A transition-metal-free procedure for the synthesis of a highly valuable class of
      heteroaromatics, quinazolines, was developed by using easily available 2
      aminobenzylamines and alpha,alpha,alpha-trihalotoluenes. The transformation
      proceeded smoothly in the presence of only sodium hydroxide and molecular oxygen
      in water at 100  degrees C, furnishing a variety of 2-aryl quinazolines. The
      crystallization process of the crude reaction mixture for the purification of the
      solid products circumvents huge solvent-consuming workup and column
      chromatographic techniques, which make the overall process more sustainable and
      economical.

PMID- 29649360
TI  - Glycerolipid Headgroups Control Rate and Mechanism of Superoxide Dismutase-1
      Aggregation and Accelerate Fibrillization of Slowly Aggregating Amyotrophic
      Lateral Sclerosis Mutants.
AB  - Interactions between superoxide dismutase-1 (SOD1) and lipid membranes might be
      directly involved in the toxicity and intercellular propagation of aggregated
      SOD1 in amyotrophic lateral sclerosis (ALS), but the chemical details of lipid
      SOD1 interactions and their effects on SOD1 aggregation remain unclear. This
      paper determined the rate and mechanism of nucleation of fibrillar apo-SOD1
      catalyzed by liposomal surfaces with identical hydrophobic chains
      (RCH2(O2C18H33)2), but headgroups of different net charge and hydrophobicity
      (i.e., R(CH2)N+(CH3)3, RPO4-(CH2)2N+(CH3)3, and RPO4-). Under semiquiescent
      conditions (within a 96 well microplate, without a gyrating bead), the
      aggregation of apo-SOD1 into thioflavin-T-positive (ThT(+)) amyloid fibrils did
      not occur over 120 h in the absence of liposomal surfaces. Anionic liposomes
      triggered aggregation of apo-SOD1 into ThT(+) amyloid fibrils; cationic liposomes
      catalyzed fibrillization but at slower rates and across a narrower lipid
      concentration; zwitterionic liposomes produced nonfibrillar (amorphous)
      aggregates. The inability of zwitterionic liposomes to catalyze fibrillization
      and the dependence of fibrillization rate on anionic lipid concentration suggests
      that membranes catalyze SOD1 fibrillization by a primary nucleation mechanism.
      Membrane-catalyzed fibrillization was also examined for eight ALS variants of apo
      SOD1, including G37R, G93R, D90A, and E100G apo-SOD1 that nucleate slower than or
      equal to WT SOD1 in lipid-free, nonquiescent amyloid assays. All ALS variants
      (with one exception) nucleated faster than WT SOD1 in the presence of anionic
      liposomes, wherein the greatest acceleratory effects were observed among variants
      with lower net negative surface charge (G37R, G93R, D90A, E100G). The exception
      was H46R apo-SOD1, which did not form ThT(+) species.

PMID- 29649361
TI  - Cytosolic Uptake of Large Monofunctionalized Dextrans.
AB  - Dextrans are a versatile class of polysaccharides with applications that span
      medicine, cell biology, food science, and consumer goods. Here, we report on a
      new type of large monofunctionalized dextran that exhibits unusual properties:
      efficient cytosolic and nuclear uptake. This dextran permeates various human cell
      types without the use of transfection agents, electroporation, or membrane
      perturbation. Cellular uptake occurs primarily through active transport via
      receptor-mediated processes. These monofunctionalized dextrans could serve as
      intracellular delivery platforms for drugs or other cargos.

PMID- 29649362
TI  - Relationship between the Physiochemical Properties of Cocoa Procyanidins and
      Their Ability to Inhibit Lipid Oxidation in Liposomes.
AB  - The aim of this paper is to evaluate the effects of cocoa polyphenols and
      procyanidins with different degrees of polymerization that are encapsulated in
      liposome delivery systems on the inhibition of lipid oxidation at pH 3.0 and 5.0.
      In general, liposomes at pH 3.0 and 5.0 were physically stable in the presence of
      polyphenols and procyanidins with mean particle sizes of 56.56 +/- 12.29 and
      77.45 +/- 8.67 nm and zeta-potentials of -33.50 +/- 3.16 and -20.44 +/- 1.98 mV
      at pH 3.0 and 5.0, respectively. At both pH 3.0 and pH 5.0, all the polyphenols
      and procyanidins inhibited lipid hydroperoxide and hexanal formation, and
      antioxidant activities increased with increasing polymer-chain sizes. The greater
      antioxidant activities of the isolated procyanidins were likely due to their
      increased metal-chelating capacities, as determined by ferric-reducing-ability
      (FRAP) assays, and their greater levels of partitioning into the lipids, as
      determined by their log Kow values and encapsulation efficiencies. The crude
      extract had the greatest antioxidant activity, which could be because other
      antioxidants were present, or combinations of the different polyphenols and
      procyanidins inhibited lipid oxidation synergistically.

PMID- 29649364
TI  - Unambiguous Signature of the Berry Phase in Intense Laser Dissociation of
      Diatomic Molecules.
AB  - We report strong evidence of Berry phase effects in intense laser dissociation of
      D2+ molecules, manifested as Aharonov-Bohm-like oscillations in the photofragment
      angular distribution (PAD). Our calculations show that this interference pattern
      strongly depends on the parity of the diatom initial rotational state, (-1) j.
      Indeed, the PAD local maxima (minima) observed in one case ( j odd) correspond to
      local minima (maxima) in the other case ( j even). Using simple topological
      arguments, we clearly show that such interference conversion is a direct
      signature of the Berry phase. The sole effect of the latter on the rovibrational
      wave function is a sign change of the relative phase between two interfering
      components, which wind in opposite senses around a light-induced conical
      intersection (LICI). Therefore, encirclement of the LICI leads to constructive (
      j odd) or destructive ( j even) self-interference of the initial nuclear
      wavepacket in the dissociative limit. To corroborate our theoretical findings, we
      suggest an experiment of strong-field indirect dissociation of D2+ molecules,
      comparing the PAD of the ortho and para molecular species in directions nearly
      perpendicular to the laser polarization axis.

PMID- 29649363
TI  - A Targeted, Differential Top-Down Proteomic Methodology for Comparison of ApoA-I
      Proteoforms in Individuals with High and Low HDL Efflux Capacity.
AB  - Top-down proteomics (TDP) allows precise determination/characterization of the
      different proteoforms derived from the expression of a single gene. In this
      study, we targeted apolipoprotein A-I (ApoA-I), a mediator of high-density
      lipoprotein cholesterol efflux (HDL-E), which is inversely associated with
      coronary heart disease risk. Absolute ApoA-I concentration and allelic variation
      only partially explain interindividual HDL-E variation. Therefore, we hypothesize
      that differences in HDL-E are associated with the abundances of different ApoA-I
      proteoforms. Here, we present a targeted TDP methodology to characterize ApoA-I
      proteoforms in serum samples and compare their abundances between individuals. We
      characterized 18 ApoA-I proteoforms using selected-ion monitoring coupled to
      electron-transfer dissociation mass spectrometry. We then compared the abundances
      of these proteoforms between two groups of four participants, representing the
      individuals with highest and lowest HDL-E values within the Chicago Healthy Aging
      Study ( n = 420). Six proteoforms showed significantly ( p < 0.0005) higher
      intensity in high HDL-E individuals: canonical ApoA-I [fold difference (fd) =
      1.17], carboxymethylated ApoA-I (fd = 1.24) and, with highest difference, four
      fatty acylated forms: palmitoylated (fd = 2.16), oleoylated (fd = 2.08),
      arachidonoylated (fd = 2.31) and one bearing two modifications: palmitoylation
      and truncation (fd = 2.13). These results demonstrate translational potential for
      targeted TDP in revealing, with high sensitivity, associations between
      interindividual proteoform variation and physiological differences underlying
      disease risk.

PMID- 29649365
TI  - Cooperative Catalysis-Enabled Asymmetric alpha-Arylation of Aldehydes Using 2
      Indolylmethanols as Arylation Reagents.
AB  - A catalytic asymmetric alpha-arylation of aldehydes using 2-indolylmethanols as
      arylation reagents has been established. This reaction was enabled by a
      cooperative catalytic system consisting of a gold complex, a Bronsted acid, and a
      chiral amine, which have a synergistic effect in the reaction process. By using
      this strategy, a series of alpha-arylation products of aldehydes were generated
      in overall acceptable yields and good enantioselectivities (up to 69%, 91:9 er).
      The control experiments demonstrated that the addition of PPh3AuCl as a gold
      complex was helpful to improve the yield, and trifluoroacetic acid as a Bronsted
      acid played a crucial role in the reaction by promoting the generation of
      carbocation and chiral enamine intermediates, which are two key intermediates of
      the asymmetric alpha-arylation reaction. In addition, the enantioselectivity of
      the reaction was mainly controlled by the chiral amine catalyst via forming a
      chiral enamine intermediate. This reaction has not only provided a useful
      protocol for catalytic asymmetric alpha-arylation of aldehydes but also enriched
      the research contents of 2-indolylmethanol-involved reactions and asymmetric
      cooperative catalysis.

PMID- 29649367
TI  - Religion as an Exchange System: The Interchangeability of God and Government in a
      Provider Role.
AB  - An exchange model of religion implies that if a secular entity such as government
      provides what people need, they will be less likely to seek help from
      supernatural entities. Controlling for quality of life and income inequality
      (Gini), we found that better government services were related to lower
      religiosity among countries (Study 1) and states in the United States (Study 2).
      Study 2 also showed that during 2008-2013, better government services in a
      specific year predicted lower religiosity 1 to 2 years later. In both studies, a
      combination of better government services and quality of life was related to a
      particularly low level of religiosity. Among countries, government services
      moderated the relation between religiosity and two measures of well-being, such
      that religiosity was related to greater well-being only when government services
      were low. We discuss the relation between the exchange model and other
      theoretical approaches to religion.

PMID- 29649366
TI  - FGF2 Enhances Odontoblast Differentiation by alphaSMA+ Progenitors In Vivo.
AB  - The goal of this study was to examine the effects of early and limited exposure
      of perivascular cells expressing alpha (alphaSMA) to fibroblast growth factor 2
      (FGF2) in vivo. We performed in vivo fate mapping by inducible Cre-loxP and
      experimental pulp injury in molars to induce reparative dentinogenesis. Our
      results demonstrate that early delivery of exogenous FGF2 to exposed pulp led to
      proliferative expansion of alphaSMA-tdTomato+ cells and their accelerated
      differentiation into odontoblasts. In vivo lineage-tracing experiments showed
      that the calcified bridge/reparative dentin in FGF2-treated pulps were lined with
      an increased number of Dspp+ odontoblasts and devoid of BSP+ osteoblasts. The
      increased number of odontoblasts derived from alphaSMA-tdTomato+ cells and the
      formation of reparative dentin devoid of osteoblasts provide in vivo evidence for
      the stimulatory effects of FGF signaling on odontoblast differentiation from
      early progenitors in dental pulp.

PMID- 29649368
TI  - Mouse Models for Studying Oral Cancer: Impact in the Era of Cancer Immunotherapy.
AB  - Model systems for oral cancer research have progressed from tumor epithelial cell
      cultures to in vivo systems that mimic oral cancer genetics, pathological
      characteristics, and tumor-stroma interactions of oral cancer patients. In the
      era of cancer immunotherapy, it is imperative to use model systems to test oral
      cancer prevention and therapeutic interventions in the presence of an immune
      system and to discover mechanisms of stromal contributions to oral cancer
      carcinogenesis. Here, we review in vivo mouse model systems commonly used for
      studying oral cancer and discuss the impact these models are having in advancing
      basic mechanisms, chemoprevention, and therapeutic intervention of oral cancer
      while highlighting recent discoveries concerning the role of immune cells in oral
      cancer. Improvements to in vivo model systems that highly recapitulate human oral
      cancer hold the key to identifying features of oral cancer initiation,
      progression, and invasion as well as molecular and cellular targets for
      prevention, therapeutic response, and immunotherapy development.

PMID- 29649369
TI  - Women with Newly Diagnosed Uterine Fibroids: Treatment Patterns and Cost
      Comparison for Select Treatment Options.
AB  - The primary objective of this study was to describe surgical treatment patterns
      among women with newly diagnosed uterine fibroids (UF). A secondary objective was
      to estimate the medical costs associated with other common surgical interventions
      for UF. Claims-based commercial and Medicare data (2011-2016) were used to
      identify women aged >=30 years with continuous enrollment for at least 12 months
      before and after a new diagnosis of UF. Receipt of a surgical or radiologic
      procedure (hysterectomy, myomectomy, endometrial ablation, uterine artery
      embolization, and curettage) was the primary outcome. Health care resource
      utilization and costs were calculated for women with at least 12 months of
      continuous enrollment following a UF surgical procedure. Among women who met
      selection criteria, 31.7% of patients underwent a surgical procedure; 20.9% of
      these underwent hysterectomy. An increase was observed over time in the
      percentage of women undergoing outpatient hysterectomy (from 27.0% to 40.2%) and
      hysteroscopic myomectomy (from 8.0% to 11.5%). The cost analysis revealed that
      total health care costs for hysteroscopic myomectomy ($17,324) were significantly
      lower (P < 0.001) than those for women who underwent inpatient hysterectomy
      ($24,027) and those for women undergoing the 3 comparison procedures.
      Hysterectomy was the most common surgical intervention. Patients undergoing
      inpatient hysterectomy had the highest health care costs. Although less
      expensive, minimally invasive approaches are becoming more common; they are
      performed infrequently in patients with newly diagnosed UF. The results of this
      study may be useful in guiding decisions regarding the most appropriate and cost
      effective surgical treatment for UF.

PMID- 29649370
TI  - The Psychosocial Impact of Cleft in a Western Australian Cohort Across 3 Age
      Groups.
AB  - BACKGROUND: Management of a cleft of the lip and/or palate (CL/P) involves a
      multidisciplinary team approach lasting from birth to potentially postskeletal
      maturity. This condition is complex, with both medical and psychosocial
      implications that may place individuals with a cleft at higher risk of developing
      psychosocial problems. METHODOLOGY: A self-administered questionnaire was
      completed by a sample from the Western Australian cleft population comprising 3
      age groups: child (n = 100), adolescent (n = 101), and adult (n = 158). RESULTS:
      Public speaking, being photographed, special relationships, and participation in
      school were identified as the areas most impacted by having a cleft. Hearing and
      speech were reported to have a higher importance than facial and dental
      appearance. Participants rated support given to them by their parents as the most
      important, with high ratings for treatment providers. For teasing, the impact of
      cleft was significantly higher among participants with cleft lip and palate for
      both the adolescent and adult age groups. There was little significant difference
      by gender across the variables, which suggests that males are just as likely to
      require support as females. CONCLUSION: The impact of a cleft across multiple
      psychosocial domains needs to be recognized and addressed as part of craniofacial
      team care across age groups.

PMID- 29649371
TI  - Subsegmental Osteotomy Technique With Distraction Osteogenesis for Natural
      Frontal Contouring in Metopic Synostosis.
AB  - Vectoring issues occur due to the dynamics of unidirectional procedure that is
      selected. To circumvent such difficulties, we have devised subsegmental osteotomy
      with distraction. In our technique, frontal bone flap was divided into 4 segments
      that were linked to each other by suturing wires in an 8-year-old patient with
      trigonocephaly. Subsegmental osteotomy and wiring of bone flap enabled us to
      slide bone in a more curvilinear manner and achieve natural contour. Distraction
      was initiated on postoperative day 7 at the rate of 1 mm/d for 20-mm gain. At the
      9-year follow-up, the patient showed improved head shape and intellectual status.

PMID- 29649372
TI  - Autogenous Bone Graft Versus Bovine Bone Graft in Association With Platelet-Rich
      Plasma for the Reconstruction of Alveolar Clefts: A Pilot Study.
AB  - OBJECTIVE: To compare the outcomes of 2 different bone graft materials:
      autogenous bone grafts from mandibular symphysis and bovine bone grafts
      associated with platelet-rich plasma (PRP). METHODS: Twenty individuals met the
      inclusion criteria and accepted to participate in the study. Group A patients
      underwent alveolar bone grafting using autologous bone and group B patients using
      a bovine bone graft associated with PRP. Cone beam computed tomography scans were
      taken and reconstructed 3-dimensionally for all patients preoperatively and 1
      year postoperatively. RESULTS: A significant reduction was detected for area and
      volume within group A and group B. Between groups, no significant difference was
      found for area or volume. CONCLUSIONS: Bovine grafts associated with PRP are a
      good option for the reconstruction of alveolar clefts and provide good results
      such as autologous bone grafts.

PMID- 29649373
TI  - IoT for Real-Time Measurement of High-Throughput Liquid Dispensing in Laboratory
      Environments.
AB  - Critical to maintaining quality control in high-throughput screening is the need
      for constant monitoring of liquid-dispensing fidelity. Traditional methods
      involve operator intervention with gravimetric analysis to monitor the gross
      accuracy of full plate dispenses, visual verification of contents, or dedicated
      weigh stations on screening platforms that introduce potential bottlenecks and
      increase the plate-processing cycle time. We present a unique solution using open
      source hardware, software, and 3D printing to automate dispenser accuracy
      determination by providing real-time dispense weight measurements via a network
      connected precision balance. This system uses an Arduino microcontroller to
      connect a precision balance to a local network. By integrating the precision
      balance as an Internet of Things (IoT) device, it gains the ability to provide
      real-time gravimetric summaries of dispensing, generate timely alerts when
      problems are detected, and capture historical dispensing data for future
      analysis. All collected data can then be accessed via a web interface for
      reviewing alerts and dispensing information in real time or remotely for timely
      intervention of dispense errors. The development of this system also leveraged 3D
      printing to rapidly prototype sensor brackets, mounting solutions, and component
      enclosures.

PMID- 29649376
TI  - Untangling Waist Circumference and Hip Circumference from Body Mass Index with a
      Body Shape Index, Hip Index, and Anthropometric Risk Indicator.
AB  - Body mass index (BMI) corrects body weight for height and is well established for
      diagnosing overweight and obesity and correlating with many medical conditions.
      Waist circumference (WC) is used to diagnose abdominal obesity. However, the
      correlation of BMI and WC is high, around 0.9, making the use of BMI and WC in
      concert challenging. A body shape index (ABSI) is a new measure of risk
      associated with abdominal size. Derived in 2012, ABSI is analogous to BMI in that
      it normalizes WC for weight and height (and thus to BMI). A similar derivation
      led to hip index (HI), normalizing hip circumference for BMI. Hazard ratios (HRs)
      for univariate risk associations of the independent measures height, BMI, ABSI,
      and HI can be multiplied to give a combined HR, the anthropometric risk indicator
      (ARI). Compared to any one anthropometric factor, including BMI and WC, ARI more
      accurately estimates personalized mortality hazard. Published work on ABSI, HI,
      and ARI supports their association with many aspects of health, including
      cardiometabolic conditions related to the metabolic syndrome.

PMID- 29649375
TI  - Anti-Podocalyxin Monoclonal Antibody 47-mG2a Detects Lung Cancers by
      Immunohistochemistry.
AB  - Lung cancer is one of the leading causes of cancer-related deaths in the world.
      Regardless of the advances in lung cancer treatments, the prognosis is still
      poor. Podocalyxin (PODXL) is a highly glycosylated type I transmembrane protein
      that is expressed in normal tissues, including the heart, pancreas, and breast.
      It is also found and used as a diagnostic marker in many cancers, such as renal,
      brain, breast, oral, and lung cancers. We previously developed specific and
      sensitive anti-PODXL monoclonal antibodies, PcMab-47 (mouse IgG1, kappa) and its
      mouse IgG2a-type (47-mG2a), both of which were suitable for immunohistochemical
      analyses of oral cancers. In this study, we investigated the utility of PcMab-47
      and 47-mG2a for the immunohistochemical analyses of lung cancers. PcMab-47
      stained 51/70 (72.9%) cases of lung cancer, whereas 47-mG2a stained 59/70 (84.3%)
      cases, indicating that the latter antibody is more sensitive and is useful for
      detecting PODXL in lung cancers.

PMID- 29649374
TI  - Precision Therapy of Head and Neck Squamous Cell Carcinoma.
AB  - Precision medicine is an approach to disease prevention and treatment that takes
      into account genetic variability and environmental and lifestyle influences that
      are unique to each patient. It facilitates stratification of patient populations
      that vary in their susceptibility to disease and response to therapy. Shared
      databases and the implementation of new technology systems designed to advance
      the integration of this information will enable health care providers to more
      accurately predict and customize prevention and treatment strategies for
      patients. Although precision medicine has had a limited impact in most areas of
      medicine, it has been shown to be an increasingly successful approach to cancer
      therapy. Despite early promising results targeting aberrant signaling pathways or
      inhibitors designed to block tumor-driven processes such as angiogenesis, limited
      success emphasizes the need to discover new biomarkers and treatment targets that
      are more reliable in predicting response to therapy and result in better health
      outcomes. Recent successes in the use of immunity-inducing antibodies have
      stimulated increased interest in the use of precision immunotherapy of head and
      neck squamous cell carcinoma. Using next-generation sequencing, the precise
      profiling of tumor-infiltrating lymphocytes has great promise to identify
      hypoimmunogenic cancer that would benefit from a rationally designed
      combinatorial approach. Continued interrogation of tumors will reveal new
      actionable targets with increasing therapeutic efficacy and fulfill the promise
      of precision therapy of head and neck cancer.

PMID- 29649377
TI  - Vitamin D Status and Cardiovascular Risk in Obesity: Effect of Physical Activity
      in Nonvitamin D Supplemented Adolescents.
AB  - BACKGROUND: The relationship among inadequate vitamin D status, obesity, and
      cardiometabolic risk and the potential impact of physical activity-based
      interventions on vitamin D status are poorly characterized in children. This
      study aimed to address these issues. METHODS: We studied a total of 21
      adolescents (15 obese and 6 normal weight; age: 14-18 years; Tanner stage>IV).
      Adolescents with obesity (n = 15) underwent a randomized controlled (8 in the
      intervention group and 7 in the control group) 3-month physical activity-based
      lifestyle intervention. 25-Hydroxy vitamin D [25(OH)D] by mass spectrometry,
      adiponectin, leptin, high-sensitivity C-reactive protein (CRP), insulin, and
      glucose were measured and body composition was assessed by dual-energy x-ray
      absorptiometry (DXA). Analysis of covariance and mixed-effects model were used to
      compare mean change in 25(OH)D between intervention and nonintervention groups.
      Bootstrap method was used to validate the estimates and principle component
      analysis reduced the variables in the data for adjustment. RESULTS: 25(OH)D was
      lower (P < 0.001) in the obese versus lean adolescents. Homeostasis model
      assessment-insulin resistance, CRP, fat mass (FM), and body mass index z-score
      were negatively correlated with baseline 25(OH)D, while adiponectin showed a
      positive correlation. After adjustment for baseline biomarkers of cardiometabolic
      risk, the concentration of 25(OH)D increased in the obese intervention group (P =
      0.06), but not in the nonintervention group. Fat-free mass increased and FM
      decreased (P < 0.05 for both) in the intervention group. The magnitudes of
      increase in 25(OH)D and decrease in FM directly correlated (P < 0.05).
      CONCLUSIONS: The increase in circulating 25(OH)D concentration by physical
      activity-based lifestyle-only intervention in adolescents with obesity, who did
      not receive vitamin D supplementation, suggests a putative independent role of
      physical activity-based interventions in the regulation of vitamin D status and
      potentially in the mitigation of risk factors of cardiovascular disease.

PMID- 29649379
TI  - Decrease of Plasma Soluble (Pro)renin Receptor by Bariatric Surgery in Patients
      with Obstructive Sleep Apnea and Morbid Obesity.
AB  - BACKGROUND: Plasma concentrations of soluble (pro)renin receptor [s(P)RR], which
      are elevated in patients with obstructive sleep apnea (OSA), have not been
      studied in morbid obesity. The aim of this study is to clarify effects of
      bariatric surgery on plasma s(P)RR concentrations and identify associated factors
      for their changes in OSA patients with morbid obesity. METHODS: Twenty-three
      patients with OSA complicated by morbid obesity (10 men and 13 women; body mass
      index, 40.7 +/- 6.16 kg/m2) without chronic kidney disease were followed up after
      bariatric surgery. Overnight polysomnography (PSG) was performed before surgery,
      and 4 and 24 weeks after surgery. Plasma s(P)RR concentrations were measured each
      morning after PSG. RESULTS: Preoperative plasma s(P)RR concentrations showed
      significant positive correlations with serum creatinine (P < 0.05), arousal index
      (P < 0.01), apnea-hypopnea index (AHI) (P < 0.05), apnea index (P < 0.005), and
      desaturation index (P < 0.05), and a significant inverse correlation with an
      estimated glomerular filtration rate (P < 0.05). With the improvement of these
      PSG parameters, plasma s(P)RR concentrations significantly decreased from 15.3 +/
      3.6 to 12.5 +/- 2.7 ng/mL 4 weeks after surgery, which further decreased to 11.4
      +/- 2.4 ng/mL 24 weeks after surgery. The association observed before surgery
      between plasma s(P)RR concentrations and the PSG parameters was not seen after
      surgery. CONCLUSIONS: Bariatric surgery in patients with OSA complicated by
      morbid obesity decreased plasma s(P)RR concentrations. The most associated
      factors for their changes were arousal index, AHI, apnea index, and desaturation
      index.

PMID- 29649380
TI  - Photobiomodulation in Light of Our Biological Clock's Inner Workings.

PMID- 29649378
TI  - Poor Sleep Quality is Associated with Insulin Resistance in Postmenopausal Women
      With and Without Metabolic Syndrome.
AB  - BACKGROUND: Poor sleep quality has previously been shown to be related to insulin
      resistance in apparently healthy adults. However, it is unclear whether an
      association between sleep quality and insulin resistance exists among adults with
      metabolic syndrome (MetS). METHODS: Participants included 347 overweight/obese
      postmenopausal women without type 2 diabetes (age: 57.5 +/- 6.5 years; body mass
      index [BMI]: 31.7 +/- 3.7 kg/m2; 54% with MetS). Sleep quality was assessed with
      the six-item Medical Outcomes Study Sleep Scale; values were categorized into
      quartiles. Insulin resistance was calculated from fasting glucose and insulin
      with the homeostasis model assessment of insulin resistance (HOMA2-IR) method.
      Analysis of covariance models were used to examine the association between sleep
      quality and HOMA2-IR after accounting for MetS and covariates (e.g., BMI,
      cardiorespiratory fitness, and energy intake). RESULTS: Women with the worst
      sleep quality had significantly higher HOMA2-IR values than women in all other
      quartiles (P <= 0.05 for each), and women with MetS had significantly higher
      HOMA2-IR values than women without MetS (P < 0.0001), but the relationship
      between sleep quality and HOMA2-IR did not differ between those with or without
      MetS (P = 0.26). Women with MetS in the worst quartile of sleep quality had
      higher HOMA2-IR values than all other women (P < 0.02). Taking >30 min to fall
      asleep, frequent restless sleep, and frequent daytime drowsiness were each
      related to higher HOMA2-IR values (each P < 0.04). CONCLUSIONS: Sleep quality is
      an important correlate of insulin resistance in postmenopausal women with and
      without MetS. Intervention studies are needed to determine whether improving
      sleep improves insulin resistance in populations at elevated cardiometabolic
      risk.

PMID- 29649381
TI  - Dying: A Memoir.

PMID- 29649382
TI  - The Role of Chaplaincy in Caring for the Seriously Ill #347.

PMID- 29649383
TI  - Treatment Options for Hepatocellular Carcinoma #348.

PMID- 29649384
TI  - Response to Davis and Behm (doi: 10.1089/jpm.2017.0608): Discontinuation of
      Statins.

PMID- 29649385
TI  - Why Smart Emerging Economies Will Invest in Excellent Palliative Care, if
      Palliative Care Services Do Their Part.

PMID- 29649386
TI  - A Salute to Our Reviewers 2017.

PMID- 29649388
TI  - The Genome-Based Metabolic Systems Engineering to Boost Levan Production in a
      Halophilic Bacterial Model.
AB  - Metabolic systems engineering is being used to redirect microbial metabolism for
      the overproduction of chemicals of interest with the aim of transforming
      microbial hosts into cellular factories. In this study, a genome-based metabolic
      systems engineering approach was designed and performed to improve biopolymer
      biosynthesis capability of a moderately halophilic bacterium Halomonas smyrnensis
      AAD6T producing levan, which is a fructose homopolymer with many potential uses
      in various industries and medicine. For this purpose, the genome-scale metabolic
      model for AAD6T was used to characterize the metabolic resource allocation,
      specifically to design metabolic engineering strategies for engineered bacteria
      with enhanced levan production capability. Simulations were performed in silico
      to determine optimal gene knockout strategies to develop new strains with
      enhanced levan production capability. The majority of the gene knockout
      strategies emphasized the vital role of the fructose uptake mechanism, and
      pointed out the fructose-specific phosphotransferase system (PTSfru) as the most
      promising target for further metabolic engineering studies. Therefore, the PTSfru
      of AAD6T was restructured with insertional mutagenesis and triparental mating
      techniques to construct a novel, engineered H. smyrnensis strain, BMA14.
      Fermentation experiments were carried out to demonstrate the high efficiency of
      the mutant strain BMA14 in terms of final levan concentration, sucrose
      consumption rate, and sucrose conversion efficiency, when compared to the AAD6T.
      The genome-based metabolic systems engineering approach presented in this study
      might be considered an efficient framework to redirect microbial metabolism for
      the overproduction of chemicals of interest, and the novel strain BMA14 might be
      considered a potential microbial cell factory for further studies aimed to design
      levan production processes with lower production costs.

PMID- 29649387
TI  - Multi-Omics Research Trends in Sepsis: A Bibliometric, Comparative Analysis
      Between the United States, the European Union 28 Member States, and China.
AB  - "-Omics" research is in transition with the recent rise of multi-omics technology
      platforms. Integration of "-omics" and multi-omics research is of high priority
      in sepsis, a heterogeneous syndrome that is widely recognized as a global health
      burden and a priority biomedical funding field. We report here an original study
      on bibliometric trends in the use of "-omics" technologies, and multi-omics
      approaches in particular, in sepsis research in three (supra)national settings,
      the United States, the European Union 28 Member States (EU-28), and China. Using
      a 5-year longitudinal bibliometric study design from 2011 to 2015, we analyzed
      the sepsis-related research articles in English language that included at least
      one or multi-omics technologies in publicly available form in Medline (free full
      texts). We found that the United States has had the lead (almost one-third of
      publications) in the inclusion of an "-omics" or multi-omics technology in sepsis
      within the study period. However, both China and the EU-28 displayed a
      significant increase in the number of publications that employed one or more
      types of "-omics" research (p < 0.005), while the EU-28 displayed a significant
      increase especially in multi-omics research articles in sepsis (p < 0.05).
      Notably, more than half of the multi-omics research studies in the sepsis
      knowledge domain had a university or government/state funding source. Among the
      multi-omics research publications in sepsis, the combination of genomics and
      transcriptomics was the most frequent (40.5%), followed by genomics and
      proteomics (20.4%). We suggest that the lead of the United States in the field of
      "-omics" and multi-omics research in sepsis is likely at stake, with both the EU
      28 and China rapidly increasing their research capacity. Moreover, "triple omics"
      that combine genomics, proteomics, and metabolomics analyses appear to be
      uncommon in sepsis, and yet much needed for triangulation of systems science
      data. These observations have implications for "-omics" technology policy and
      global research funding strategic foresight.

PMID- 29649390
TI  - Trends and Racial/Ethnic Disparities in Pneumococcal Polysaccharide Vaccination.
AB  - Even though pneumococcal vaccination recommendations have been in existence since
      1983, vaccination rates are low in the United States. This study analyzed 5-year
      trends in pneumococcal polysaccharide vaccination uptake across racial/ethnic
      groups of individuals aged >=65 years and high-risk individuals aged 19-64 years.
      Further, it examined factors that may explain the association between
      race/ethnicity and vaccination uptake. The 2011-2015 annual Behavioral Risk
      Factor Surveillance System (BRFSS) data were used to determine trends. The
      Behavioral Model of Health Care Utilization was used to identify covariates in
      the model. Multivariate logistic regressions were used to identify the
      association between race/ethnicity and vaccination uptake from 2015 BRFSS.
      Overall, from 2011 to 2015, vaccination uptake increased moderately from 69% to
      71% among those aged >=65 years, and from 21% to 24% for high-risk individuals
      aged 19-64 years. Among those aged >=65 years (n = 99,403), African Americans
      (adjusted odds ratio [AOR]: 1.36, 95%CI: 1.21-1.52) and Hispanics (AOR: 2.13,
      95%CI: 1.85-2.46) were more likely to be vaccinated than Whites. Among the
      younger population (n = 177,976), African Americans (AOR: 0.85, 95%CI: 0.79-0.92)
      and Asians (AOR: 0.73, 95%CI: 0.63-0.84) were less likely to be vaccinated than
      Whites. Over the 5 years there were no significant increases in vaccination
      uptake. The rates are far below the Healthy People 2020 goals. Reverse
      disparities were observed in the older group. In younger group, minorities were
      less likely to get vaccinated. As gaps still exist, this study implies tailored
      interventions based on race/ethnicity to promote vaccination uptake among both
      groups.

PMID- 29649391
TI  - Patients' Medication-Related Experience of Care Is Associated with Adherence to
      Cardiometabolic Disease Therapy in Real-World Clinical Practice.
AB  - Adherence to cardiometabolic disease (CMD) medications is typically suboptimal.
      This study sought to evaluate the relationship between patients' medication
      related experiences of care and adherence to CMD therapy. This study was
      conducted using electronic health records and administrative data from an
      ambulatory care setting. It included adult managed care beneficiaries with a
      prescription for CMD medications (antihyperlipidemic, antihypertensive, or
      antihyperglycemic agents) between 2010 and 2014, written +/-14 days of an office
      encounter linked to a completed patient experience survey. Outcomes were primary
      and overall adherence. Primary adherence was defined as ever filling a CMD
      medication and overall adherence as >=80% days covered over 365 days among those
      with an initial fill. Survey items ("inclusion in treatment decisions" and
      "information about medications") are measured on a scale from 1 (very poor) to 5
      (very good). Logistic regression was used to assess associations between ratings
      on each item (5 vs. <5) and primary or overall adherence. Eligibility criteria
      were met by 7368 patients; 5865 had >=1 fill. After adjusting for confounders,
      better patient experiences with "inclusion in treatment decisions" (adjusted odds
      ratio [OR]:1.16; P = 0.049) and "information about medications" (OR:1.22; P =
      0.009) were associated with greater odds of overall adherence to therapy. No
      significant associations were found between patient experience and primary
      adherence. Better patient medication-related experience of care is associated
      with improved adherence to CMD therapy. Efforts to include patients in treatment
      decision making and to provide better education on medications are simple,
      modifiable solutions to improve adherence and resultant outcomes of CMD
      treatment.

PMID- 29649389
TI  - Cost-Effectiveness Analysis of a Standardized Management Program for Ischemic
      Stroke Patients in Hainan Province, China.

PMID- 29649392
TI  - Assessing Potentially Preventable Hospitalizations at the County Level: A
      Comparison of Measures Using Medicare Data and State Hospital Discharge Data.
AB  - This study examined the representativeness of the County Health Rankings and
      Roadmaps (CHR) measure of potentially preventable hospitalizations, which is
      derived from Medicare inpatient claims data, as an indicator of potentially
      preventable hospitalizations for adults aged >=18 years. Potentially preventable
      hospitalizations were evaluated using rates of ambulatory care sensitive
      conditions (ACSCs). CHR rates of hospitalization for ACSCs based on Medicare data
      for 2010, Agency for Healthcare Research and Quality Prevention Quality Indicator
      #90 Overall Composite (PQI #90 Composite) rates of ACSCs based on hospital
      inpatient data for adults aged >=18 years for 2011, and 2011 total mortality
      rates for adults aged >=18 years for 212 counties in 3 US states were evaluated.
      Pearson correlation analyses were used to assess the linear association between
      the PQI #90 Composite and CHR rates of hospitalization for ACSCs as well as
      associations of these measures with total mortality. Steiger's Z-test was
      conducted to examine whether the PQI #90 Composite and CHR measures of health
      care quality were similarly correlated with total mortality. The age- and sex
      adjusted PQI #90 Composite for adults >=18 years was moderately correlated with
      the CHR rate of hospitalization for ACSCs. The PQI #90 Composite and CHR measures
      of hospitalization for ACSCs were similarly correlated with mortality. These
      findings suggest that in the absence of easily accessible, high-quality data for
      adults aged >=18 years, the CHR measure of potentially preventable
      hospitalizations provides a modest but acceptable approximation of county-level
      disparities in potentially preventable hospitalizations for the US adult
      population.

PMID- 29649393
TI  - Effectiveness of Psychosocial Interventions in Complex Palliative Care Patients:
      A Quasi-Experimental, Prospective, Multicenter Study.
AB  - OBJECTIVE: To determine whether specific psychosocial interventions can ease
      discomfort in palliative care (PC) patients, particularly in those with high
      levels of pain or emotional distress. METHODS: Changes in the psychological
      parameters of 8333 patients were assessed in a quasi-experimental, prospective,
      multicenter, single group pretest/post-test study. Psychosocial care was
      delivered by 29 psychosocial care teams (PSTs; 137 professionals). Pre- and post
      intervention changes in these variables were assessed: mood, anxiety, and
      emotional distress. Patients were classified as complex, when presented with high
      levels of anxiety, mood, suffering (or perception of time as slow), and distress
      (or unease, or discomfort), or noncomplex. These groups were compared to assess
      changes in suffering-related parameters from baseline. RESULTS: Psychosocial
      interventions reduced patients' suffering. These interventions were more
      effective in complex patients. CONCLUSIONS: After successive psychosocial
      interventions, the level of suffering in complex patients decreased until close
      to parity with noncomplex patients, suggesting that patients with major
      complexity could benefit most from specific psychosocial treatment. These
      findings support the importance of assessing and treating patients' psychosocial
      needs.

PMID- 29649394
TI  - Perspective on Care at the End of Life at Hospice Africa Uganda.
AB  - BACKGROUND: Since its beginning in 1993, Hospice Africa Uganda (HAU) has become a
      leader in palliative care in Africa. Despite this, there remains a sparsity of
      research elucidating the priorities of patients in their care at the end of life.
      This study aimed to identify those priorities in three groups: patients with life
      limiting illness, their caregivers, and their healthcare providers at HAU, and
      thus to identify differences in what these groups find important in the last
      month of life. METHODS: A Likert scale survey of 31 statements regarding end-of
      life care was administered to 46 patients, 51 caregivers, and 25 healthcare
      providers at HAU in Kampala, Uganda and satellite locations. ANALYSIS: Variations
      in the responses of the groups were analyzed using the Kruskal-Wallis test of
      variance. RESULTS: Twelve of 31 items were significantly different, and frequency
      data were examined. Differences were found in categories of symptom management,
      future planning, and in preferred place of death. Of anxiety, pain, and shortness
      of breath (SOB), only control of SOB was widely agreed on as important by
      patients, although providers unanimously wanted to control symptoms. Many
      subjects in all groups found that funeral arrangements should be deferred. Most
      patients and caregivers felt as if dying in the hospital was preferable, whereas
      providers felt that home care was preferable. CONCLUSION: This study tells us
      that patients, caregivers, and healthcare providers often have different ideas
      concerning what is important in end-of-life care, differences that are unique to
      this population.

PMID- 29649395
TI  - Top Ten Tips Palliative Care Clinicians Should Know When Caring for Patients with
      Endometrial Cancer.
AB  - Endometrial cancer incidence has been increasing over the last two decades,
      likely due to the obesity epidemic. The majority of these cancers are confined to
      the uterus at diagnosis and can be cured with surgery. Overall, five-year disease
      specific survival is about 80%, but some patients have locally advanced or
      metastatic disease that is not amenable to control with radiation and/or
      chemotherapy. Disease-related symptoms are most common in this subset of patients
      with endometrial cancer, although women with early-stage disease may also
      experience side effects related to surgical menopause or adjuvant treatment. In
      recent years, professional societies have been increasingly vocal about the
      importance of incorporating palliative care early in a patient's disease course.
      As these calls increase, palliative care clinicians will likely increasingly
      comanage patients with advanced or recurrent endometrial cancer. We brought
      together a team of gynecologic oncology and palliative care experts to assemble
      practical tips for the care of women with endometrial cancer. In this article, we
      use a "Top 10" format to highlight issues that may help palliative care
      physicians understand a patient's prognosis, address common misconceptions about
      endometrial cancer, and improve the quality of shared decision making and goals
      of care discussions.

PMID- 29649397
TI  - Management of a Cancer Patient with an Intrathecal Drug Delivery System and an
      Acute Brain Abscess.
AB  - Surgical-site infection, spinal cord abscess, and catheter tip granuloma are
      known but rare complications of intrathecal drug delivery systems (IDDS). To
      date, there are no published cases of brain abscess in a patient with an IDDS. In
      this study, we report a case of a cancer patient with an IDDS for management of
      cancer pain who developed a brain abscess with profound mental status changes and
      clinical management challenges.

PMID- 29649396
TI  - Surgeons' Perceived Barriers to Palliative and End-of-Life Care: A Mixed Methods
      Study of a Surgical Society.
AB  - BACKGROUND: Nearly 20% of colorectal cancer (CRC) patients present with
      potentially incurable (Stage IV) disease, yet their physicians do not integrate
      cancer treatment with palliative care. Compared with patients treated by primary
      providers, surgical patients with terminal diseases are significantly less likely
      to receive palliative or end-of-life care. OBJECTIVE: To describe surgeon
      perspectives on palliative and end-of-life care for patients with Stage IV CRCs.
      DESIGN: This is a convergent mixed methods study using a validated survey
      instrument from the Critical Care Peer Workgroup of the Robert Wood Johnson
      Foundation's Promoting Excellence in End-of-Life Care Project with additional
      qualitative questions. SETTINGS: Participants were all current, nonretired
      members of the American Society of Colon and Rectal Surgeons. MAIN OUTCOME
      MEASURES: Surgeon-perceived barriers to palliative and end-of-life care for
      patients with Stage IV CRCs were identified. RESULTS: Among 131 Internet survey
      respondents (response rate 16.5%), 76.1% reported no formal education in
      palliative care, and specifically noted inadequate training in techniques to
      forgo life-sustaining measures (37.9%) and communication (42.7%). Over half
      (61.8%) of surgeons cited unrealistic expectations among patients and families as
      a barrier to care, which also limited discussion of palliation. At the system
      level, absence of documentation, appropriate processes, and culture hindered the
      initiation of palliative care. Thematic analysis of open-ended questions
      confirmed and extended these findings through the following major barriers to
      palliative and end-of-life care: (1) surgeon knowledge and training; (2)
      communication challenges; (3) difficulty with prognostication; (4) patient and
      family factors encompassing unrealistic expectations and discordant preferences;
      and (5) systemic issues including culture and lack of documentation and
      appropriate resources. LIMITATIONS: Generalizability is limited by the small
      sample size inherent to Internet surveys, which may contribute to selection bias.
      CONCLUSIONS: Surgeons valued palliative and end-of-life care but reported
      multilevel barriers to its provision. These data will inform strategies to reduce
      these perceived barriers.

PMID- 29649398
TI  - Feasibility and Patient Perceptions of Video Declarations Regarding End-of-Life
      Decisions by Hospitalized Patients.
AB  - BACKGROUND: A videotaped declaration by patients of their advance care planning
      preferences could be an opportunity to supplement advance directive forms and be
      a source of information for family, caregivers, and clinicians, yet research is
      needed to examine the content and acceptability of making declarations among
      patients. OBJECTIVE: To evaluate the content and acceptability of 'video
      declarations': the process of patients videotaping themselves describing their
      advance care planning preferences. DESIGN: We showed a brief video describing
      three approaches to end-of-life care and then invited participants to use an iPad
      to videotape themselves making a declaration about their wishes.
      SETTING/SUBJECTS: Hospitalized patients from a large urban U.S. safety net
      hospital. MEASUREMENTS: We interviewed participants about the acceptability of
      the declaration process. Declarations were transcribed and coded by a team, with
      multiple stakeholder input. RESULTS: There were 16 participants; mean age was 60
      (SD = 14) years. One participant declined. Out of 15 declarations, most were able
      to express their wishes for CPR (n = 12) and intubation (n = 13). Participants
      frequently discussed their family structure (n = 11), religious/spiritual well
      being (n = 8), legacy/dignity issues (n = 6), and physical symptoms (n = 6). Nine
      declarations had directives judged to be unclear. The majority (66%) thought that
      this process was quite a bit or extremely helpful. CONCLUSIONS: Findings show
      that asking hospitalized patients to make videos describing their advance care
      planning preferences was feasible and acceptable. While the majority described
      their wishes around CPR and intubation, a fair amount of uncertainty remained.
      Further research is needed to support patients in describing their wishes clearly
      and test the effectiveness of video declarations to promote care concordant with
      preferences.

PMID- 29649399
TI  - A Rules-Based Algorithm to Prioritize Poor Prognosis Cancer Patients in Need of
      Advance Care Planning.
AB  - BACKGROUND: Accurate understanding of the prognosis of an advanced cancer patient
      can lead to decreased aggressive care at the end of life and earlier hospice
      enrollment. OBJECTIVE: Our goal was to determine the association between high
      risk clinical events identified by a simple, rules-based algorithm and decreased
      overall survival, to target poor prognosis cancer patients who would urgently
      benefit from advanced care planning. DESIGN: A retrospective analysis was
      performed on outpatient oncology patients with an index visit from April 1, 2015,
      through June 30, 2015. We examined a three-month window for "high-risk events,"
      defined as (1) change in chemotherapy, (2) emergency department (ED) visit, and
      (3) hospitalization. Patients were followed until January 31, 2017.
      SETTING/SUBJECTS: A total of 219 patients receiving palliative chemotherapy at
      the University of Chicago Medicine with a prognosis of <=12 months were included.
      MEASUREMENTS: The main outcome was overall survival, and each "high-risk event"
      was treated as a time-varying covariate in a Cox proportional hazards regression
      model to calculate a hazard ratio (HR) of death. RESULTS: A change in
      chemotherapy regimen, ED visit, hospitalization, and at least one high-risk event
      occurred in 54% (118/219), 10% (22/219), 26% (57/219), and 67% (146/219) of
      patients, respectively. The adjusted HR of death for patients with a high-risk
      event was 1.72 (95% confidence interval [CI] 1.19-2.46, p = 0.003), with
      hospitalization reaching significance (HR 2.74, 95% CI 1.84-4.09, p < 0.001).
      CONCLUSIONS: The rules-based algorithm identified those with the greatest risk of
      death among a poor prognosis patient group. Implementation of this algorithm in
      the electronic health record can identify patients with increased urgency to
      address goals of care.

PMID- 29649400
TI  - Impact of Inpatient Palliative Care on Quality of End-of-Life Care and Downstream
      Acute and Postacute Care Utilization.
AB  - BACKGROUND: Additional evidence is needed regarding the impact of inpatient
      palliative care (IPC) on the quality of end-of-life care and downstream
      utilization. AIM: Examine the effects of IPC on quality of end-of-life care and
      acute and postacute care use in a large integrated system. DESIGN: Retrospective
      cohort design. SETTING/PARTICIPANTS: Adult decedents from January 1, 2012, to
      December 31, 2014, who had at least one hospitalization at 11 Kaiser Permanente
      Southern California medical centers in the 12 months before death and not
      hospitalized for a trauma-related condition or receiving home-based PC or hospice
      were included in the cohort. MATERIALS AND METHODS: Inverse probability of
      treatment weighting of propensity scores was used to compare outcomes between
      patients exposed to IPC (n = 3742) and controls (n = 12,755) who never received
      IPC before death. RESULTS: Patients who received IPC were more likely to enroll
      in home-based PC or hospice (69% vs. 43%) and were less likely to die in a
      hospital (15% vs. 29%) or intensive care (2% vs. 9%) compared with controls (all,
      p < 0.001). IPC exposure was associated with higher risk for rehospitalization
      (HR: 1.18, 95% CI 1.11-1.25) and more frequent emergency department visits (RR:
      1.16, 95% CI 1.07-1.26) with no increase in postacute care use compared with
      controls. Stratified analyses showed that IPC effects on acute care utilization
      were dependent on code status. CONCLUSION: IPC exposure was associated with
      higher enrollment in home-based PC/hospice and more deaths at home. The increased
      acute care utilization by the IPC group may reflect persistent confounding by
      indication.

PMID- 29649401
TI  - Intrahospital Mortality and Survival of Patients with Advanced Chronic Illnesses
      in a Tertiary Hospital Identified with the NECPAL CCOMS-ICO(c) Tool.
AB  - BACKGROUND: Between 69% and 82% of patients with advanced chronic illness require
      palliative care (PC). The NECPAL CCOMS-ICO(c) tool can identify these
      individuals. Tools to estimate survival are available, but have limited
      predictive ability, and therefore we sought to assess if NECPAL could improve
      survival prediction. OBJECTIVE: To describe hospital mortality, survival rates,
      and related variables in a sample of inpatients identified with the NECPAL tool.
      DESIGN: Cross-sectional study with longitudinal cohort follow-up.
      Sociodemographic and clinical data were analyzed. A predictive model (Cox
      regression analysis) was performed to assess survival. SETTING/SUBJECTS: Patients
      admitted to a tertiary hospital. Included patients were considered to be
      especially affected by their chronic condition and NECPAL+ patients (surprise
      question [SQ]+ plus >=1 of the tool's other three criteria). Patients were
      classified into three subgroups: non-NECPAL (either SQ- or not meeting any
      additional NECPAL criteria); NECPAL I-II (SQ+ with one to two additional
      criteria); and NECPAL III (SQ+ with all three additional criteria). RESULTS: Of
      the 602 inpatients, 236 (39.2%) were included. Of these, 49 (20.3%) died during
      hospitalization: 14 (13.3%) were NECPAL I-II; 34 (35.1%) were NECPAL III; and
      none were non-NECPAL (p < 0.001). At two years, 146 deaths (61.9%) were observed:
      9 (26.5%) non-NECPAL; 57 (54.3%) NECPAL I-II; and 80 (82.5%) NECPAL III (p <
      0.001). Median survival was 9.1 months. Variables associated with higher
      mortality were NECPAL III classification (hazard ratio [HR]: 1.75 [1.19-2.57]);
      in need of PC (HR: 2 [1.27-3.13]); dysphagia (HR: 1.7 [1.12-2.58] 6); cancer (HR:
      3.21 [2.19-4.71]); and age >85 years (HR: 2.52 [1.46-4.35]). At six months, the
      NECPAL had an area under the curve (AUC) of 0.7 (95% confidence interval [CI]:
      0.632-0.765), and at 24 months, the NECPAL AUC was 0.717 (95% CI: 0.650-0.785).
      CONCLUSIONS: The NECPAL CCOMS-ICO(c) tool can improve the prediction of
      mortality. The presence of all three NECPAL criteria (NECPAL III) increases the
      tool's predictive ability.

PMID- 29649402
TI  - End-of-Life Treatments in Pediatric Patients at a Government Tertiary Cancer
      Center in India.
AB  - AIM: The primary objective of this study was to describe demographics and end-of
      life treatments of children with cancer at a government tertiary cancer center in
      India. METHODS: A retrospective review was undertaken of medical charts of all
      children younger than 18 years, who died as inpatients while undergoing treatment
      at the pediatric oncology department between April and September 2016. Data were
      collected on demographics, diagnosis, treatments, survival, palliative care
      involvement, and symptoms at end of life. RESULTS: There were 44 pediatric
      oncology patients who died in the hospital during the study period. The most
      frequent diagnoses were hematological malignancies (n = 29). Tumor-specific
      treatment was given to 38/44 (86%) patients in the last 30 days of life, and 13
      patients in the last day of life or 1 day before. Of all deaths, 23/44 (52%)
      occurred within 30 days of admission to the pediatric ward and 34/44 (77%) within
      90 days. Of the 44 patients, 25 (57%) were referred to palliative care. The
      median number of days between referral and death was 14 (0-78) days. Frequent
      symptoms documented were bleeding (11/44), dyspnea (10/44), pain (7/44), seizures
      (7/44), and delirium (5/44), with each patient having one or more of these
      symptoms. Only patients with a palliative care referral received opioid
      analgesics or benzodiazepines at the end of life. CONCLUSIONS: This study
      highlights the demographics of suffering, death, and end-of-life care in children
      with cancer at a government tertiary cancer center in India.

PMID- 29649403
TI  - The "ARIANNA" Project: An Observational Study on a Model of Early Identification
      of Patients with Palliative Care Needs through the Integration between Primary
      Care and Italian Home Palliative Care Units.
AB  - OBJECTIVE: The aim of this study was to illustrate the characteristics of
      patients with palliative care (PC) needs, early identified by general
      practitioners (GPs), and to analyze their care process in home PC services.
      BACKGROUND: Early identification and service integration are key components to
      providing quality palliative care (PC) services ensuring the best possible
      service for patients and their families. However, in Italy, PC is often provided
      only in the last phase of life and for oncological patients, with a fragmented
      service. METHODS: Multicenter prospective observational study, lasting in total
      18 months, implemented in a sample of Italian Home Palliative Care Units (HPCUs),
      enrolling and monitoring patients with limited life expectancy, early identified
      by 94 GPs. The study began on March 1, 2014 and ended on August 31, 2015.
      RESULTS: Nine hundred thirty-seven patients, out of a total pool of 139,071, were
      identified by GPs as having a low life expectancy and PC needs. Of these, 556
      (59.3%) were nononcological patients. The GPs sent 433 patients to the HPCUs for
      multidimensional assessment, and 328 (75.8%) were placed in the care of both
      settings (basic or specialist). For all patients included in the study, both
      oncological and nononcological patients, there was a high rate of death at home,
      around 70%. DISCUSSION: This study highlights how a model based on early
      identification, multidimensional evaluation, and integration of services can
      promote adequate PC, also for noncancer patients, with a population-based
      approach.

PMID- 29649404
TI  - Development of Valid and Reliable Measures of Patient and Family Experiences of
      Hospice Care for Public Reporting.
AB  - BACKGROUND: Increasingly, dying patients and their families have a choice of
      hospice providers. Care quality varies considerably across providers; informing
      consumers of these differences may help to improve their selection of hospices.
      OBJECTIVE: To develop and evaluate standardized survey measures of hospice care
      experiences for the purpose of comparing and publicly reporting hospice
      performance. DESIGN: We assessed item performance and constructed composite
      measures by factor analysis, evaluating item-scale correlations and estimating
      reliability. To assess key drivers of overall experiences, we regressed overall
      rating and willingness to recommend the hospice on each composite.
      SETTING/SUBJECTS: Data submitted by 2500 hospices participating in national
      implementation of the Consumer Assessment of Healthcare Providers and Systems
      (CAHPS(r)) Hospice Survey for April through September 2015. MEASUREMENTS:
      Composite measures of Hospice Team Communication, Getting Timely Care, Treating
      Family Member with Respect, Getting Emotional and Religious Support, Getting Help
      for Symptoms, and Getting Hospice Care Training. RESULTS: Cronbach's alpha
      estimates for the composite measures range from 0.61 to 0.85; hospice-level
      reliability for the measures range from 0.67 to 0.81 assuming 200 completed
      surveys per hospice. Together, the composites are responsible for 48% of the
      variance in caregivers' overall ratings of hospices. Hospice Team Communication
      is the strongest predictor of overall rating of care. CONCLUSION: Our analyses
      provide evidence of the reliability and validity of CAHPS Hospice Survey measure
      scores. Results also highlight important opportunities to improve the quality of
      hospice care, particularly with regard to addressing symptoms of anxiety and
      sadness, discussing side effects of pain medicine, and keeping family informed of
      the patient's condition.

PMID- 29649405
TI  - Economic Impact of Early Inpatient Palliative Care Intervention in a Community
      Hospital Setting.
AB  - BACKGROUND: Inpatient palliative care programs have demonstrated financial
      benefit for the hospital and improved quality of care for patients with advanced
      disease. Previous studies on this subject have focused on comparisons between
      palliative and traditional care. The financial and clinical effects of early
      versus late palliative care intervention are less well documented. OBJECTIVE: The
      aims of this study are to review the financial and quality outcomes that early
      palliative care intervention has on appropriate inpatients in the community
      hospital setting. MATERIALS AND METHODS: This retrospective study analyzed 449
      palliative care patients. The independent variable was days to palliative care
      consultation, characterized as early palliative care (<=3 days) and late
      palliative care (>3 days). Dependent variables included length of stay (LOS) and
      financial considerations. The two groups were further stratified according to
      case mix index, medical versus surgical, as well as certain disease groups, such
      as sepsis, congestive heart failure (CHF), and chronic obstructive pulmonary
      disease (COPD) exacerbation. The patient's functional status, measured by the
      Victoria Palliative Performance Scale (PPSv2) was calculated to determine if this
      variable independently influenced the timing of consultation. RESULTS: Patients
      in the early intervention group realized a reduction in LOS and a significant
      cost reduction. In the analysis of the entire group, the average LOS with early
      intervention was 6.09 days versus 16.5 days with late intervention (p < 0.001).
      The early intervention group demonstrated an earlier transition to comfort care,
      earlier referral to outpatient hospice, and did not have a negative effect on
      mortality. The patient's PPSv2 score did not influence the timing of intervention
      (p 0.25). CONCLUSION: Early intervention with inpatient palliative care
      consultation correlated with financial benefit as well as earlier referral to
      more appropriate levels of care. These effects were achieved with minimal expense
      in a medium-sized community hospital.

PMID- 29649407
TI  - Undermining the ACA through the executive branch and federalism: what the Trump
      administration's approach to health reform means for older Americans.
AB  - The ACA has survived multiple existential threats in the legislative and judicial
      branches, including dozens of congressional attempts at repeal and two major
      Supreme Court cases. Even as it seems that the ACA is here to stay, what the law
      accomplishes is far from settled. The Trump administration is using executive
      powers to weaken the law, in many cases using the same powers that President
      Obama used to strengthen the effects of the reform. States have responded by
      seeking flexibility to pursue reforms, such as work requirements, that could not
      pass Congress and that were not allowed by the Obama administration. There is no
      indication that the ACA is imploding as President Trump has predicted and seems
      to desire, although these changes have a real and substantial impact on the lives
      of many Americans, including the near-elderly in unique ways.

PMID- 29649409
TI  - The Forkhead Transcription Factor FOXC2 Is Required for Maintaining Murine
      Spermatogonial Stem Cells.
AB  - Continuous spermatogenesis from puberty to old age in males relies on
      spermatogonial stem cells (SSCs) that possess the property of self-renewal and
      differentiation. The delicate balance between self-renewal and differentiation is
      of great importance. In mice, SSCs exist as a subpopulation of undifferentiated
      spermatogonia. SSCs are controlled by intrinsic molecular pathways that can be
      activated by extrinsic signals. Our results here first show that the expression
      of forkhead box C2 (FOXC2) is restricted to GFRalpha1-positive spermatogonia in
      the testis. Whole-mount immunofluorescence results reveal that FOXC2 is expressed
      predominately in As and Apr spermatogonia. Reduction of Foxc2 gene expression by
      shRNA lentivirus treatment significantly impairs the maintenance of SSCs in
      vitro. Furthermore, knock-down of Foxc2 decreases SSC colonization to only 10.42%
      compared to the control by transplantation. Reverse transcription and real-time
      quantitative PCR gene analyses following knock-down of Foxc2 indicate that Foxc2
      may act as a suppressor for SSC differentiation. Extrinsic stimuli treatments
      show that glial cell line-derived neurotrophic factor and retinoic acid act in
      opposite ways to regulate FOXC2 expression and subsequent SSC property. These
      results suggest that FOXC2 is a critical intrinsic regulator of SSC self-renewal
      and differentiation.

PMID- 29649408
TI  - Interferon-Gamma Impairs Maintenance and Alters Hematopoietic Support of Bone
      Marrow Mesenchymal Stromal Cells.
AB  - Bone marrow (BM) mesenchymal stromal cells (MSCs) provide microenvironmental
      support to hematopoietic stem and progenitor cells (HSPCs). Culture-expanded MSCs
      are interesting candidates for cellular therapies due to their immunosuppressive
      and regenerative potential which can be further enhanced by pretreatment with
      interferon-gamma (IFN-gamma). However, it remains unknown whether IFN-gamma can
      also influence hematopoietic support by BM-MSCs. In this study, we elucidate the
      impact of IFN-gamma on the hematopoietic support of BM-MSCs. We found that IFN
      gamma increases expression of interleukin (IL)-6 and stem cell factor by human BM
      MSCs. IFN-gamma-treated BM-MSCs drive HSPCs toward myeloid commitment in vitro,
      but impair subsequent differentiation of HSPC. Moreover, IFN-gamma-ARE-Del mice
      with increased IFN-gamma production specifically lose their BM-MSCs, which
      correlates with a loss of hematopoietic stem cells' quiescence. Although IFN
      gamma treatment enhances the immunomodulatory function of MSCs in a clinical
      setting, we conclude that IFN-gamma negatively affects maintenance of BM-MSCs and
      their hematopoietic support in vitro and in vivo.

PMID- 29649410
TI  - Sca1+Lin-CD117- Mouse Bone Marrow-Derived Mesenchymal Stem Cells Regulate
      Immature Dendritic Cell Maturation by Inhibiting TLR4-IRF8 Signaling Via the
      Notch-RBP-J Pathway.
AB  - Mesenchymal stem cells (MSCs) have a superior immunomodulatory capacity compared
      to other cells of the immune system, and they hold great promise for treating
      various immune disorders. However, their regulatory effects on the maturation of
      immature dendritic cells (imDCs) are not fully understood. In this study, we show
      that Sca-1+Lin-CD117-MSCs restrain the lipopolysaccharide-stimulated maturation
      transition of imDCs cocultured without exogenous cytokines. The Notch signaling
      pathway plays a critical role in the process by controlling interferon regulatory
      factor 8 (IRF8) expression in an RBP-J-dependent manner. We observed a high
      degree of H3K27me3 modification mediated by SUZ12 and a relatively low degree of
      H3K4me3 modification regulated by WDR5 at the IRF8 promoter during coculture.
      These data reveal a possible mechanism by which Sca-1+Lin-CD117-MSCs modulate
      imDC maturation and further support the role of MSCs in treating immune
      disorders.

PMID- 29649411
TI  - The In Vitro Differentiation of GDNF Gene-Engineered Amniotic Fluid-Derived Stem
      Cells into Renal Tubular Epithelial-Like Cells.
AB  - Amniotic fluid is an alternative source of stem cells, and human amniotic fluid
      derived stem cells (AFSCs) obtained from a small amount of amniotic fluid
      collected during the second trimester represent a novel source for use in
      regenerative medicine. These AFSCs are characterized by lower diversity, a higher
      proliferation rate, and a wider differentiation capability than adult mesenchymal
      stem cells. AFSCs are selected based on the cell surface marker c-kit receptor
      (CD117) using immunomagnetic sorting. Glial cell line-derived neurotrophic factor
      (GDNF) is expressed during early kidney development and regulates the
      proliferation and differentiation of stem cells in vitro. In this study, c-kit
      sorted AFSCs were induced toward osteogenic or adipogenic differentiation. AFSCs
      engineered via the insertion of GDNF were cocultured with mouse renal tubular
      epithelial cells (mRTECs), which were preconditioned by hypoxia-reoxygenation in
      vitro. After coculture for 8 days, AFSCs differentiation into epithelial-like
      cells was evaluated by performing immunofluorescence, flow cytometry, and
      quantitative real-time polymerase chain reaction to identify cells expressing the
      renal epithelial markers, cytokeratin 18 (CK18), E-cadherin, aquaporin-1 (AQP1),
      and paired box 2 gene (Pax2). The GDNF gene enhanced AFSCs differentiation into
      RTECs. AFSCs possess self-renewal ability and multiple differentiation potential
      and thus represent a new source of stem cells.

PMID- 29649413
TI  - Neural Stem Cells Derived Directly from Adipose Tissue.
AB  - Neural stem cells (NSCs) are characterized as self-renewing cell populations with
      the ability to differentiate into the multiple tissue types of the central
      nervous system. These cells can differentiate into mature neurons, astrocytes,
      and oligodendrocytes. This category of stem cells has been shown to be a
      promisingly effective treatment for neurodegenerative diseases and neuronal
      injury. Most treatment studies with NSCs in animal models use embryonic brain
      derived NSCs. This approach presents both ethical and feasibility issues for
      translation to human patients. Adult tissue is a more practical source of stem
      cells for transplantation therapies in humans. Some adult tissues such as adipose
      tissue and bone marrow contain a wide variety of stem cell populations, some of
      which have been shown to be similar to embryonic stem cells, possessing many
      pluripotent properties. Of these stem cell populations, some are able to respond
      to neuronal growth factors and can be expanded in vitro, forming neurospheres
      analogous to cells harvested from embryonic brain tissue. In this study, we
      describe a method for the collection and culture of cells from adipose tissue
      that directly, without going through intermediates such as mesenchymal stem
      cells, results in a population of NSCs that are able to be expanded in vitro and
      be differentiated into functional neuronal cells. These adipose-derived NSCs
      display a similar phenotype to those directly derived from embryonic brain. When
      differentiated into neurons, cells derived from adipose tissue have spontaneous
      spiking activity with network characteristics similar to that of neuronal
      cultures.

PMID- 29649412
TI  - Continuous Exposure to Simulated Hypergravity-Induced Changes in Proliferation,
      Morphology, and Gene Expression of Human Tendon Cells.
AB  - Gravity influences physical and biological processes, especially during
      development and homeostasis of several tissues in the human body. Studies under
      altered gravity have been receiving great attention toward a better understanding
      of microgravity-, hypogravity (<1 g)-, or hypergravity (>1 g)-induced
      alterations. In this work, the influence of simulated hypergravity over human
      tendon-derived cells (hTDCs) was studied at 5, 10, 15, and 20 g for 4 or 16 h,
      using a large diameter centrifuge. Main results showed that 16 h of simulated
      hypergravity limited cell proliferation. Cell area was higher in hTDCs cultured
      at 5, 10, and 15 g for 16 h, in comparison to 1 g control. Actin filaments were
      more pronounced in hTDCs cultured at 5 and 10 g for 16 h. Focal adhesion kinase
      (FAK) was mainly expressed in focal adhesion sites upon hypergravity stimulation,
      in comparison to perinuclear localization in control cells after 16 h; and FAK
      number/cell increased with increasing g-levels. A tendency toward an upregulation
      of tenogenic markers was observed; scleraxis (SCX), tenascin C (TNC), collagen
      type III (COL3A1), and decorin (DCN) were significantly upregulated in hTDCs
      cultured at 15 g and COL3A1 and DCN were significantly upregulated in hTDCs
      cultured at 20 g. Overall, simulated hypergravity affected the behavior of hTDCs,
      with more pronounced effects in the long-term period (16 h) of stimulation.

PMID- 29649414
TI  - miR-450b Promotes Osteogenic Differentiation In Vitro and Enhances Bone Formation
      In Vivo by Targeting BMP3.
AB  - Osteoporosis is characterized by deterioration of bone microarchitecture and low
      bone mass. One of the primary causes of osteoporosis is the decrease in the
      osteogenic differentiation of mesenchymal stem cells (MSCs). Tissue engineering
      therapy with genetically modified MSCs has attracted much attention in the study
      of bone regeneration. In this study, we found that the expression level of miR
      450b was upregulated during osteogenic differentiation of human adipose-derived
      mesenchymal stem cells (hADSCs). To explore the effect of miR-450b on the
      osteogenesis of hADSCs, we performed a series of gain- and loss-of-function
      analyses and demonstrated that miR-450b not only promoted the process of hADSC
      differentiation to osteoblasts in vitro but also enhanced ectopic bone formation
      in vivo. Bone morphogenetic protein 3 (BMP3), the most abundant BMP member in
      bone, was identified as a direct target of miR-450b. Downregulation of the
      endogenous expression of BMP3 could mimic the effect of miR-450b upregulation on
      the osteogenic differentiation of hADSCs. Overall, our study first demonstrated
      that a novel microRNA miR-450b was essential for hADSC differentiation, which
      could promote osteogenic differentiation in vitro and enhance bone formation in
      vivo by directly suppressing BMP3.

PMID- 29649415
TI  - Generation of Neural Organoids from Human Embryonic Stem Cells Using the Rotary
      Cell Culture System: Effects of Microgravity on Neural Progenitor Cell Fate.
AB  - Progress in aeronautics and spaceflight technologies requires in parallel further
      research on how microgravity may affect human tissue. To date, little is known
      about the effects of microgravity on human development. In this study we used the
      rotary cell culture system to investigate whether microgravity supports the
      generation and maintenance of neural organoids derived from human embryonic stem
      cells (hESCs) as a model of human brain development. Our results show that
      although neural organoids could be generated and maintained in microgravity
      conditions, there were changes in expression of rostral-caudal neural patterning
      genes and cortical markers compared to organoids generated in standard
      conditions. This phenomenon was also observed in hESC-derived cortical organoids
      exposed to microgravity for relatively shorter periods. These results are one of
      the first for analyzing human neurogenesis in a microgravity environment.

PMID- 29649416
TI  - Improving Mechanical Properties of Molded Silicone Rubber for Soft Robotics
      Through Fabric Compositing.
AB  - Molded silicone rubbers are common in manufacturing of soft robotic parts, but
      they are often prone to tears, punctures, and tensile failures when strained. In
      this article, we present a fabric compositing method for improving the mechanical
      properties of soft robotic parts by creating a fabric/rubber composite that
      increases the strength and durability of the molded rubber. Comprehensive ASTM
      material tests evaluating the strength, tear resistance, and puncture resistance
      are conducted on multiple composites embedded with different fabrics, including
      polyester, nylon, silk, cotton, rayon, and several blended fabrics. Results show
      that strong fabrics increase the strength and durability of the composite,
      valuable in pneumatic soft robotic applications, while elastic fabrics maintain
      elasticity and enhance tear strength, suitable for robotic skins or soft strain
      sensors. Two case studies then validate the proposed benefits of the fabric
      compositing for soft robotic pressure vessel applications and soft strain sensor
      applications. Evaluations of the fabric/rubber composite samples and devices
      indicate that such methods are effective for improving mechanical properties of
      soft robotic parts, resulting in parts that can have customized stiffness,
      strength, and vastly improved durability.

PMID- 29649417
TI  - Corrigendum to "Association of glycated albumin to HbA1c ratio with diabetic
      retinopathy but not diabetic nephropathy in patients with type 2 diabetes" [Clin.
      Biochem. 50 (2017) 270-273].

PMID- 29649420
TI  - Disparities in the Health of Women and Children.

PMID- 29649418
TI  - Roles of progesterone receptor membrane component 1 and membrane progestin
      receptor alpha in regulation of zebrafish oocyte maturation.
AB  - Although previous studies suggest membrane progesterone receptor alpha
      (mPRalpha/Paqr7) mediates 17, 20beta-dihydroxy-4-pregnen-3-one (DHP) induction of
      oocyte maturation (OM) in zebrafish, critical information needed to establish
      mPRalpha as the receptor mediating OM is lacking. The relative potencies of
      progestins and specific mPRalpha agonists in inducing OM matched their relative
      binding affinities for zebrafish mPRalpha, supporting its role in OM.
      Microinjection of pertussis toxin blocked DHP induction of OM and the progestin
      induced decrease in cyclic AMP levels, suggesting mPRalpha activates an
      inhibitory G protein (Gi). Microinjection of morpholino antisense
      oligonucleotides to zebrafish pgrmc1 blocked induction of OM by DHP which was
      accompanied by decreased levels of Pgrmc1 and mPRalpha on the oocyte plasma
      membranes. Similarly, treatment of denuded oocytes with a PGRMC1 inhibitor,
      AG205, blocked the gonadotropin-induced increase in plasma membrane mPRalpha
      levels and attenuated DHP induction of OM. Co-incubation with two inhibitors of
      epidermal growth factor Erbb2, ErbB2 inhibitor II and AG 879, prevented induction
      of OM by DHP, indicating the likely involvement of Erbb2 in mPRalpha-mediated
      signaling. Treatment with AG205 reversed the inhibitory effects of the Erbb2
      inhibitors on OM and also inhibited insulin-like growth factor-1 induction of OM.
      Close associations between Pgrmc1 and mPRalpha, and between Pgrmc1 and Erbb2 were
      detected in zebrafish oocytes with in situ proximity ligation assays. The results
      suggest progestin induction of OM in zebrafish is mediated through an
      mPRalpha/Gi/Erbb2 signaling pathway that requires Pgrmc1 for expression of
      mPRalpha on oocyte membranes and that Pgrmc1 also is required for induction of OM
      through Erbb2.

PMID- 29649419
TI  - Factor Structure and Psychometric Properties of the Neonatal Eating Assessment
      Tool-Breastfeeding.
AB  - The purpose of this study was to identify the factor structure of the Neonatal
      Eating Assessment Tool-Breastfeeding (NeoEAT-Breastfeeding) and to assess its
      psychometric properties, including internal consistency reliability, test-retest
      reliability, and construct validity as measured by concurrent and known-groups
      validity. Exploratory factor analysis conducted on responses from 402 parents of
      breastfeeding infants younger than 7 months old showed a 62-item measure with
      seven subscales and acceptable internal consistency reliability (Cronbach's alpha
      = .92). Test-retest reliability was also acceptable (r = .91). The NeoEAT
      Breastfeeding has evidence of concurrent validity with the Infant
      Gastroesophageal Reflux Questionnaire (r = .69) and Infant Gastrointestinal
      Symptoms Questionnaire (r = .62). The NeoEAT-Breastfeeding total score and all
      subscale scores were higher in infants with feeding problems than in typically
      feeding infants (p < .001, known-groups validity). The NeoEAT-Breastfeeding is a
      parent-report assessment of breastfeeding in infants from birth to 7 months old
      with good initial evidence of reliability and validity.

PMID- 29649421
TI  - Editorial Comment.

PMID- 29649422
TI  - Editorial Comment.

PMID- 29649424
TI  - The Safety and Efficacy of Supraciliary Stenting Following Failed Glaucoma
      Surgery.
AB  - PURPOSE: To evaluate the safety and efficacy of supraciliary stenting following
      failed glaucoma surgery. DESIGN: Interventional case series. METHODS: Setting:
      Moorfields Eye Hospital, London, United Kingdom. STUDY POPULATION: Twenty eyes
      from 20 patients with glaucoma refractory to prior glaucoma surgery.
      INTERVENTION: Ab interno microstent (CyPass Micro-Stent; Alcon, Fort Worth,
      Texas, USA) implantation into the supraciliary space. MAIN OUTCOME MEASURES:
      Outcome measures included the occurrence of ocular adverse events, mean
      intraocular pressure (IOP) change, and glaucoma medication use through 12 months.
      RESULTS: Mean baseline IOP was 22.5 +/- 8.0 mm Hg and number of medications was
      2.7 +/- 1.0. The majority of patients had undergone either prior trabeculectomy
      or aqueous shunt surgery. There were no serious intraoperative complications or
      major adverse events following supraciliary stenting. The most common adverse
      events included transient hyphema (3/20, 15%), transient IOP > 30 mm Hg (4/20,
      20%), and transient IOP < 6 mm Hg (4/20, 20%). At 12 months, mean IOP was 14.9 +/
      4.3 mm Hg-a 33.7% reduction (P = .01). Mean medication usage decreased 56% to
      1.2 +/- 1.5 at 12 months (P = .01). Two patients (10%) required subsequent
      aqueous shunt insertion. CONCLUSION: Ab interno supraciliary stenting has a
      favorable safety profile and provides an effective approach to controlling IOP
      and reducing medication burden in eyes in which previous glaucoma surgery has
      failed.

PMID- 29649425
TI  - Effects of grape consumption on biomarkers of inflammation, endothelial function,
      and PBMC gene expression in obese subjects.
AB  - This study investigated effects of grape consumption on biomarkers of
      cardiovascular health in obese participants in both postprandial and chronic
      settings. Twenty obese adults participated in this randomized, placebo
      controlled, double-blinded crossover trial. Participants were randomized to
      consume 60 g freeze-dried polyphenol-rich whole grape powder (GP) or placebo
      (PBO) followed by high fat high carbohydrate (HFHC) meal challenge. Following
      acute challenge, participants consumed their respective treatment daily for 4
      weeks to determine effects of chronic consumption. Consumption of GP with HFHC
      meal significantly increased nuclear factor (erythroid-derived 2)-like 2 (NRF2)
      expression in peripheral blood mononuclear cells (PBMC) at 3 h (p < 0.05) and
      decreased plasma endothelin-1 (ET-1) concentration at 5 h (p < 0.05) after meal
      challenge compared with PBO. Following 4 weeks of daily GP consumption, soluble
      vascular cell adhesion molecule 1 (sVCAM-1) plasma concentration increased
      compared with PBO (p < 0.05), however baseline values differed between
      treatments. In conclusion, GP consumption resulted in decreased vasoconstrictor
      ET-1 concentration and increased gene expression related to oxidative stress
      defense following HFHC meal. Except for increase in sVCAM-1 concentration, 4
      weeks of chronic GP consumption had little effect on cardiovascular biomarkers
      measured in this study. This trial was registered: clinicaltrials.gov
      NCT01674231.

PMID- 29649426
TI  - Centers for Disease Control-type light traps equipped with high-intensity light
      emitting diodes as light sources for monitoring Anopheles mosquitoes.
AB  - In this study the phototactic response of anopheline mosquitoes to different
      luminous intensity light-emitting diodes (LEDs) was investigated. Centers for
      Disease Control-type light traps were changed by replacement of the incandescent
      lamps by 5 mm round type green (520 nm) and blue (470 nm) LEDs of different
      luminous intensities: green-LED traps with luminous intensities of 10,000, 15,000
      and 20,000 millicandela (mcd) and the blue-LED traps with luminous intensities of
      4000, 12,000 and 15,000 mcd. Our data showed that increasing luminous intensity
      has an effect on the attraction of anopheline mosquitoes to light traps,
      highlighting the importance of taking LEDs and light sources of high luminous
      intensity into account when using light-trap collections in monitoring
      populations of Anopheles species.

PMID- 29649427
TI  - VEGFR-3 signaling is regulated by a G-protein activator, activator of G-protein
      signaling 8, in lymphatic endothelial cells.
AB  - Vascular endothelial growth factor C (VEGFC) and its cognate receptor VEGFR-3
      play a key role in lymphangiogenesis. We previously reported that an ischemia
      inducible Gbetagamma signal regulator, activator of G-protein signaling 8 (AGS8),
      regulated the subcellular distribution of vascular endothelial growth factor
      receptor-2 (VEGFR-2) and influenced VEGFA-induced signaling in vascular
      endothelial cells. Here, we report that AGS8 regulates VEGFR-3, which is another
      subtype of the VEGF receptor family, and mediates VEGFC signaling in human dermal
      lymphatic endothelial cells (HDLECs). VEGFC stimulated the proliferation of
      HDLECs and tube formation by HDLECs, which were inhibited by knocking down AGS8
      by small interfering RNA (siRNA). AGS8 siRNA inhibited VEGFC-mediated
      phosphorylation of VEGFR-3 and its downstream molecules, including ERK1/2 and
      AKT. Analysis of fluorescence-activated cell sorting and immunofluorescence
      staining demonstrated that AGS8 knockdown was associated with a reduction of
      VEGFR-3 at the cell surface. Endocytosis inhibitors did not rescue the decrease
      of cell-surface VEGFR-3, suggesting that AGS8 regulated the trafficking of VEGFR
      3 to the plasma membrane. An immunoprecipitation assay indicated that VEGFR-3
      formed a complex including AGS8 and Gbetagamma in cells. These data suggest the
      novel regulation of VEGFC-VEGFR-3 by AGS8 in HDLECs and a potential role for AGS8
      in lymphangiogenesis.

PMID- 29649428
TI  - Connections of annexin A1 and translocator protein-18 kDa on toll like receptor
      stimulated BV-2 cells.
AB  - BACKGROUND: Annexin A1 (ANXA1) and Translocator Protein-18KDa (TSPO) down
      regulate neuroinflammation. We investigated the role of recombinant ANXA1 (rANXA)
      on TSPO functions on Toll Like Receptor (TLR) activated microglia. METHODS: BV-2
      cells (murine microglia), were stimulated by E. coli Lipopolysaccharide (LPS) and
      treated with rANXA1 in order to measure TSPO expression and inflammatory
      parameters. Anti-sense ANXA1 and TLR4 and TSPO shRNA, as well as pharmacological
      treatments, were employed to assess the mechanisms involved. RESULTS: LPS
      stimulated BV-2 cells caused overexpression of TSPO, which was inhibited by:
      pharmacological blockade of TLR4 or TLR4 mRNA silencing; inhibition of myeloid
      differentiation primary response gene 88 (MyD88) dimerization; or blocking of
      nuclear factor kappaB (NF-kappaB) activation. rANXA1 treatment impaired LPS
      induced TSPO upregulation by down-modulating MyD88 and NF-kappaB signaling; the
      effect was abolished by WRW4, an antagonist of formyl peptide receptor 2 (FPR2).
      rANXA1 treatment also downregulated interleukin 1beta (IL-1beta) and tumor
      necrosis factor-alpha (TNFalpha) secretion in LPS-stimulated BV-2 cells. TSPO
      knockdown in BV-2 cells augmented LPS-induced TNFalpha secretion and abolished
      the inhibitory effect of rANXA1 on TNFalpha secretion evoked by LPS. CONCLUSIONS:
      exogenous ANXA1 down-modulates LPS-induced TSPO via MyD-88/NF-kappaB pathways,
      and constitutive TSPO is pivotal for the control of ANXA1 on TNFalpha secretion.
      TSPO actions may be involved with the mechanisms of ANXA1 on inflammatory brain
      diseases.

PMID- 29649430
TI  - Dynamics analysis of SIR epidemic model with correlation coefficients and
      clustering coefficient in networks.
AB  - In this paper, the correlation coefficients between nodes in states are used as
      dynamic variables, and we construct SIR epidemic dynamic models with correlation
      coefficients by using the pair approximation method in static networks and
      dynamic networks, respectively. Considering the clustering coefficient of the
      network, we analytically investigate the existence and the local asymptotic
      stability of each equilibrium of these models and derive threshold values for the
      prevalence of diseases. Additionally, we obtain two equivalent epidemic
      thresholds in dynamic networks, which are compared with the results of the mean
      field equations.

PMID- 29649429
TI  - Deletion of the insulin receptor in sensory neurons increases pancreatic insulin
      levels.
AB  - Insulin is known to have neurotrophic properties and loss of insulin support to
      sensory neurons may contribute to peripheral diabetic neuropathy (PDN). Here,
      genetically-modified mice were generated in which peripheral sensory neurons
      lacked the insulin receptor (SNIRKO mice) to determine whether disrupted sensory
      neuron insulin signaling plays a crucial role in the development of PDN and
      whether SNIRKO mice develop symptoms of PDN due to reduced insulin neurotrophic
      support. Our results revealed that SNIRKO mice were euglycemic and never
      displayed significant changes in a wide range of sensorimotor behaviors, nerve
      conduction velocity or intraepidermal nerve fiber density. However, SNIRKO mice
      displayed elevated serum insulin levels, glucose intolerance, and increased
      insulin content in the islets of Langerhans of the pancreas. These results
      contribute to the growing idea that sensory innervation of pancreatic islets is
      key to regulating islet function and that a negative feedback loop of sensory
      neuron insulin signaling keeps this regulation in balance. Our results suggest
      that a loss of insulin receptors in sensory neurons does not lead to peripheral
      nerve dysfunction. The SNIRKO mice will be a powerful tool to investigate sensory
      neuron insulin signaling and may give a unique insight into the role that sensory
      neurons play in modifying islet physiology.

PMID- 29649431
TI  - Diagnosis and Management of Children With Mycobacterium abscessus Infections in
      the Head and Neck.
AB  - PURPOSE: Controversy exists regarding the most appropriate treatment strategy for
      children with nontuberculous mycobacterial (NTM) cervical lymphadenitis.
      Mycobacterium abscessus (MAB) is an uncommon cause of NTM cervical lymphadenitis.
      The purpose of the present study was to evaluate diagnosis, management, and
      treatment outcomes in children with MAB-associated cervical lymphadenitis
      resulting from a pulpotomy. MATERIALS AND METHODS: This was a retrospective chart
      review of children with NTM lymphadenitis of the head and neck caused by MAB
      treated at Children's Healthcare of Atlanta hospitals (Atlanta, GA). The
      predictor variables were patient demographics, dental history, clinical
      presentation, imaging characteristics, laboratory findings, histopathologic
      examination, treatment, and complications. The outcome variable was disease
      resolution or persistence. RESULTS: Twenty-two patients (mean age, 6.5 yr) met
      the inclusion criteria. All patients had pulpotomy at 1 dental practice. The mean
      time from dental procedure to symptom onset was 43.1 days (range, 3 to 180 days).
      Children presented with cervical or submandibular swelling, facial swelling,
      gingival erythema, and skin erythema. Radiographic findings were submandibular or
      cervical lymphadenitis, maxillary or mandibular osteolysis, subcutaneous abscess,
      and pulmonary nodules. All children had confirmed or probable MAB infection
      diagnosed on the pathologic specimen. There were 2 distinct patient presentations
      that guided surgical management: isolated noninflammatory cervical lymphadenitis,
      which was partly or completely excised (n = 11), and adjacent extension or
      disseminated infection requiring subtotal lymph node excision, bone debridement,
      and postoperative antibiotics (n = 11). Most children required multiple surgical
      interventions to remove infected tissues. All achieved clinical resolution.
      CONCLUSION: In this cohort, treatment of NTM lymphadenitis caused by MAB depended
      on extent of disease and virulence of bacteria. When complete surgical excision
      was possible, disease resolution was achieved. However, in cases with adjacent
      extension or dissemination infection, postoperative antibiotics were necessary.

PMID- 29649432
TI  - Nitric oxide signaling regulates tumor-induced intussusceptive-like angiogenesis.
AB  - Existing animal models for screening tumor angiogenic process have various
      setbacks that necessitate further investigations. In this study, we developed an
      ex-ovo egg yolk angiogenesis model to screen the angiogenic potency of tumor
      cells (HeLa and SiHa cell lines). The egg yolk angiogenesis assay was applied to
      study the nitric oxide (NO) influence on switching from sprouting angiogenesis
      (SA) to intussusceptive angiogenesis (IA) under tumor microenvironment.
      Morphological analysis and SA-like or IA-like markers expression were determined
      during the development of chicken chorioallantoic membrane (CAM) from day 5 to
      13. Expression of Notch1, Notch2, EphrinB2, and Tie2 were considered as SA-like
      while TEM8, CALD1, CXCR4 and HOMX1 were followed as IA-like markers. The HeLa and
      SiHa cell lines embedded CAM showed an increase in micro and macro blood vessels
      and vascular size, junction and length which are the pivotal morphological
      parameters of angiogenesis. Further, the study revealed that HeLa is more
      aggressive than SiHa in inducing tumor angiogenesis. To determine the NO
      signaling implication in tumor milieu, NO donor (Spermine NONOate (SPNO)), NOS
      inhibitor (L-nitro-L-arginine-methyl ester (L-NAME) and VEGF inhibitor (Avastin)
      were administrated to chick embryo vascular bed with and without HeLa cells. The
      results demonstrated that HeLa cells promote IA through NO signaling, VEGF and
      eNOS and it was documented by angiogenic morphological parameters and SA-like or
      IA-like markers expression. Therefore, our study claims that ex-ovo egg yolk
      angiogenesis model could be used to study tumor angiogenesis and NO plays a key
      role in switching of IA under tumor microenvironment.

PMID- 29649433
TI  - Repurposing sex steroids and related drugs as potential treatment for Parkinson's
      disease.
AB  - Parkinson's disease (PD) is a neurodegenerative disorder for which a greater
      prevalence and incidence is described in men. This suggests a protective effect
      of sex hormones in the brain. Therefore, steroids and drugs to treat endocrine
      conditions could have additional application for PD. Here, we review the
      protective effect of sex hormones, particularly estrogens, progesterone,
      androgens and dehydroepiandrosterone, in animal models of PD and also in human
      studies. Data also support that drugs affecting estrogen neurotransmission such
      as selective estrogen receptor modulators or affecting steroid metabolism with
      5alpha-reductase inhibitors could be repositioned for treatment of PD. Sex
      steroids are also modulator of neurotransmission, thus they could repurposed to
      treat PD motor symptoms and to modulate the response to PD medication. No drug is
      yet available to limit PD progression. PD is a complex disease implicating
      multiple pathological processes and a therapeutic strategy using drugs with
      several mechanisms of action, such as sex steroids and endocrine drugs are
      interesting repositioning options for symptomatic treatment and disease-modifying
      activity for PD.

PMID- 29649434
TI  - Evaluation of an Allosteric BACE Inhibitor Peptide to Identify Mimetics that Can
      Interact with the Loop F Region of the Enzyme and Prevent APP Cleavage.
AB  - The aspartyl protease BACE1 (BACE) has emerged as an appealing target for
      reduction of amyloid-beta in Alzheimer's disease. The clinical fate of active
      site BACE inhibitors may depend on potential side effects related to enzyme and
      substrate selectivity. One strategy to reduce this risk is through development of
      allosteric inhibitors that interact with and modulate the Loop F region unique to
      BACE1. Previously, a BACE-inhibiting antibody (Ab) was shown by co
      crystallization to bind and induce conformational changes of Loop F, resulting in
      backbone perturbations at the distal S6 and S7 subsites, preventing proper
      binding of a long APP-like substrate to BACE and inhibiting its cleavage. In an
      effort to discover small Loop F-interacting molecules that mimic the Ab
      inhibition, we evaluated a peptide series with a YPYF(I/L)P(L/Y) motif that was
      reported to bind a BACE exosite. Our studies show that the most potent inhibitor
      from this series, peptide 65007, has a similar substrate cleavage profile to the
      Ab and reduces sAPPbeta levels in cell models and primary neurons. As our
      modeling indicates, it interacts with the Loop F region causing a conformational
      shift of the BACE protein backbone near the distal subsites. The peptide-bound
      enzyme adopts a conformation that closely overlays with the crystal structure
      (PDB: 3R1G) from Ab binding. Importantly, peptide 65007 appears to be BACE
      substrate and enzyme selective, showing little inhibition of NRG1, PSGL1, CHL1,
      or Cat D. Thus, peptide 65007 is a promising lead for discovery of Loop F
      interacting small-molecule mimetics as allosteric inhibitors of BACE.

PMID- 29649435
TI  - Food for Gut: Microbiota Fuels Immune Reconstitution after BMT.
AB  - The host factors that modulate hematopoietic reconstitution after bone marrow
      transplantation are poorly understood. In this issue of Cell Host & Microbe,
      Staffas et al. (2018) demonstrate that gut microbiota play a critical role in
      immune reconstitution after bone marrow transplantation, partly through dietary
      energy harvest and uptake.

PMID- 29649436
TI  - ATAC-ing Transcriptional Mysteries in Malaria Parasites.
AB  - Ever since Plasmodium intraerythrocytic development was reported to proceed via
      an unusual "hardwired" transcriptional cascade, the control of gene transcription
      in malaria parasites has been an area of intense investigation. In this issue of
      Cell Host & Microbe, Toenhake et al. (2018) illuminate this intriguing issue by
      applying ATAC sequencing.

PMID- 29649437
TI  - Turning Up Your Nose for a Flaviviral Encephalitis Cure.
AB  - siRNA approaches have demonstrated promise in treating viral infections in animal
      models, but poor delivery limits clinical application. In this issue of Cell Host
      & Microbe, Beloor et al. (2018) report that nose-to-brain delivery of viral
      targeted siRNA cures mice from West Nile virus encephalitis, with potential
      implications for human infection.

PMID- 29649438
TI  - Immunity by Design.
AB  - One outcome of the many advances in basic sciences that have been made over the
      last decades is the prospect of rational vaccine design. A recent publication by
      Du et al. (2018) describes a screening method for selection of live-attenuated
      viral vaccine platforms with enhanced immune-stimulatory properties.

PMID- 29649439
TI  - Time Heals All Wounds ... But Wounds Heal Faster with Lactobacillus.
AB  - Chronic nonhealing wounds represent a significant clinical problem and cost the
      healthcare system $19 billion annually. Recently, Vagesjo et al. (2018)
      demonstrated a promising therapeutic approach for nonhealing wounds with topical
      application of CXCL12-producing Lactobacilli that enhanced healing through
      alterations in the wound microenvironment.

PMID- 29649440
TI  - Mapping the Evolutionary Potential of RNA Viruses.
AB  - The deterministic force of natural selection and stochastic influence of drift
      shape RNA virus evolution. New deep-sequencing and microfluidics technologies
      allow us to quantify the effect of mutations and trace the evolution of viral
      populations with single-genome and single-nucleotide resolution. Such experiments
      can reveal the topography of the genotype-fitness landscapes that shape the path
      of viral evolution. By combining historical analyses, like phylogenetic
      approaches, with high-throughput and high-resolution evolutionary experiments, we
      can observe parallel patterns of evolution that drive important phenotypic
      transitions. These developments provide a framework for quantifying and
      anticipating potential evolutionary events. Here, we examine emerging
      technologies that can map the selective landscapes of viruses, focusing on their
      application to pathogenic viruses. We identify areas where these technologies can
      bolster our ability to study the evolution of viruses and to anticipate and
      possibly intervene in evolutionary events and prevent viral disease.

PMID- 29649441
TI  - Small Intestine Microbiota Regulate Host Digestive and Absorptive Adaptive
      Responses to Dietary Lipids.
AB  - The gut microbiota play important roles in lipid metabolism and absorption.
      However, the contribution of the small bowel microbiota of mammals to these diet
      microbe interactions remains unclear. We determine that germ-free (GF) mice are
      resistant to diet-induced obesity and malabsorb fat with specifically impaired
      lipid digestion and absorption within the small intestine. Small bowel microbes
      are essential for host adaptation to dietary lipid changes by regulating gut
      epithelial processes involved in their digestion and absorption. In addition, GF
      mice conventionalized with high-fat diet-induced jejunal microbiota exhibit
      increased lipid absorption even when fed a low-fat diet. Conditioned media from
      specific bacterial strains directly upregulate lipid absorption genes in murine
      proximal small intestinal epithelial organoids. These findings indicate that
      proximal gut microbiota play key roles in host adaptability to dietary lipid
      variations through mechanisms involving both the digestive and absorptive phases
      and that these functions may contribute to conditions of over- and
      undernutrition.

PMID- 29649442
TI  - The Receptor-like Cytoplasmic Kinase BIK1 Localizes to the Nucleus and Regulates
      Defense Hormone Expression during Plant Innate Immunity.
AB  - Plants employ cell-surface pattern recognition receptors (PRRs) to detect
      pathogens. Although phytohormones produced during PRR signaling play an essential
      role in innate immunity, a direct link between PRR activation and hormone
      regulation is unknown. EFR is a PRR that recognizes bacterial EF-Tu and activates
      immune signaling. Here we report that EFR regulates the phytohormone jasmonic
      acid (JA) through direct phosphorylation of a receptor-like cytoplasmic kinase,
      BIK1. The BIK1 structure revealed that the EFR-phosphorylated sites reside on a
      uniquely extended loop away from the BIK1 kinase core domain. Phosphomimetic
      mutations of these sites resulted in increased phytohormones and enhanced
      resistance to bacterial infections. In addition to its documented plasma membrane
      localization, BIK1 also localizes to the nucleus and interacts directly with WRKY
      transcription factors involved in the JA and salicylic acid (SA) regulation.
      These findings demonstrate the mechanistic basis of signal transduction from PRR
      to phytohormones, mediated through a PRR-BIK1-WRKY axis.

PMID- 29649443
TI  - Immunization with AgTRIO, a Protein in Anopheles Saliva, Contributes to
      Protection against Plasmodium Infection in Mice.
AB  - Plasmodium infection begins with the bite of an anopheline mosquito, when
      sporozoites along with saliva are injected into a vertebrate host. The role of
      the host responses to mosquito saliva components in malaria remains unclear. We
      observed that antisera against Anopheles gambiae salivary glands partially
      protected mice from mosquito-borne Plasmodium infection. Specifically, antibodies
      to A. gambiae TRIO (AgTRIO), a mosquito salivary gland antigen, contributed to
      the protection. Mice administered AgTRIO antiserum showed lower Plasmodium liver
      burden and decreased parasitemia when exposed to infected mosquitoes. Active
      immunization with AgTRIO was also partially protective against Plasmodium berghei
      infection. A combination of AgTRIO antiserum and antibodies against Plasmodium
      circumsporozoite protein, a vaccine candidate, further decreased P. berghei
      infection. In humanized mice, AgTRIO antiserum afforded some protection against
      mosquito-transmitted Plasmodium falciparum. AgTRIO antiserum reduced the movement
      of sporozoites in the murine dermis. AgTRIO may serve as an arthropod-based
      target against Plasmodium to combat malaria.

PMID- 29649444
TI  - Single HIV-1 Imaging Reveals Progression of Infection through CA-Dependent Steps
      of Docking at the Nuclear Pore, Uncoating, and Nuclear Transport.
AB  - The HIV-1 core consists of capsid proteins (CA) surrounding viral genomic RNA.
      After virus-cell fusion, the core enters the cytoplasm and the capsid shell is
      lost through uncoating. CA loss precedes nuclear import and HIV integration into
      the host genome, but the timing and location of uncoating remain unclear. By
      visualizing single HIV-1 infection, we find that CA is required for core docking
      at the nuclear envelope (NE), whereas early uncoating in the cytoplasm promotes
      proteasomal degradation of viral complexes. Only docked cores exhibiting
      accelerated loss of CA at the NE enter the nucleus. Interestingly, a CA mutation
      (N74D) altering virus engagement of host factors involved in nuclear transport
      does not alter the uncoating site at the NE but reduces the nuclear penetration
      depth. Thus, CA protects HIV-1 complexes from degradation, mediates docking at
      the nuclear pore before uncoating, and determines the depth of nuclear
      penetration en route to integration.

PMID- 29649446
TI  - Dysbiosis-Associated Change in Host Metabolism Generates Lactate to Support
      Salmonella Growth.

PMID- 29649447
TI  - Age-Associated Microbial Dysbiosis Promotes Intestinal Permeability, Systemic
      Inflammation, and Macrophage Dysfunction.

PMID- 29649445
TI  - Chromatin Accessibility-Based Characterization of the Gene Regulatory Network
      Underlying Plasmodium falciparum Blood-Stage Development.
AB  - Underlying the development of malaria parasites within erythrocytes and the
      resulting pathogenicity is a hardwired program that secures proper timing of gene
      transcription and production of functionally relevant proteins. How stage
      specific gene expression is orchestrated in vivo remains unclear. Here, using the
      assay for transposase accessible chromatin sequencing (ATAC-seq), we identified
      ~4,000 regulatory regions in P. falciparum intraerythrocytic stages. The vast
      majority of these sites are located within 2 kb upstream of transcribed genes and
      their chromatin accessibility pattern correlates positively with abundance of the
      respective mRNA transcript. Importantly, these regions are sufficient to drive
      stage-specific reporter gene expression and DNA motifs enriched in stage-specific
      sets of regulatory regions interact with members of the P. falciparum AP2
      transcription factor family. Collectively, this study provides initial insights
      into the in vivo gene regulatory network of P. falciparum intraerythrocytic
      stages and should serve as a valuable resource for future studies.

PMID- 29649448
TI  - Retraction Notice to: The Unfolded Protein Response Element IRE1alpha Senses
      Bacterial Proteins Invading the ER to Activate RIG-I and Innate Immune Signaling.

PMID- 29649449
TI  - Specifying What We Study and Implement in Rehabilitation: Comments on the
      Reporting of Clinical Research.
AB  - Several guidelines have been published with the goal of increasing the usefulness
      of reports of clinical research. Although such guidelines may clarify key
      features of study design, the way in which rehabilitation treatments themselves
      are described continues to be problematic and limits the ability to replicate
      research, synthesize evidence across studies, or apply these treatments in
      practice. Lohse et al report little improvement in the description of
      rehabilitation treatments in recent years, with particular limitations in the
      description of comparison or standard-of-care treatments. This commentary
      explores the kind of published treatment descriptions that would be most useful
      in supporting evidence synthesis and clinical implementation and examines the
      degree to which a developing conceptual framework-the Rehabilitation Treatment
      Specification System-might support improvements in research reporting.

PMID- 29649450
TI  - Mandated Quality of Care Metrics for Medicare Patients: Examining New or Worsened
      Pressure Ulcers and Rehabilitation Outcomes in United States Inpatient
      Rehabilitation Facilities.
AB  - OBJECTIVE: To examine the association between the Medicare pressure ulcer quality
      indicator (the development of new or worsened pressure ulcers) and rehabilitation
      outcomes among Medicare patients seen in an inpatient rehabilitation facility
      (IRF). DESIGN: Retrospective descriptive study. SETTING: IRFs subscribed to the
      Uniform Data System for Medical Rehabilitation. PARTICIPANTS: Nearly 500,000 IRF
      Medicare patients who were discharged between January 2013 and September 2014
      were examined. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Functional
      independence, functional change (gain), and discharge destination. RESULTS: The
      pressure ulcer quality indicator was associated with poorer rehabilitation
      outcomes; patients were less likely to achieve functional independence (odds
      ratio [OR], .47; 95% confidence interval [CI], .44-.51), were less likely to be
      discharged to a community setting (OR, .88; 95% CI, .82-.95), and made less
      functional gain during their IRF stay (a difference of 6 FIM points).
      CONCLUSIONS: These results support that the pressure ulcer quality indicator is
      associated with lower quality of rehabilitation outcomes; however, given that
      those patients with a new or worsened pressure injury still made functional gains
      and most were discharged to the community, the risk of pressure injury
      development should not preclude the admission of these cases to an IRF.

PMID- 29649451
TI  - Associations Between Muscle Synergies and Treatment Outcomes in Cerebral Palsy
      Are Robust Across Clinical Centers.
AB  - OBJECTIVE: To determine whether patient-specific differences in motor control
      quantified using muscle synergy analysis were associated with changes in gait
      after treatment of cerebral palsy (CP) across 2 clinical centers with different
      treatments and clinical protocols. DESIGN: Retrospective cohort study. SETTING:
      Clinical medical center. PARTICIPANTS: Center 1: children with CP (n=473) and
      typically developing (TD) children (n=84). Center 2: children with CP (n=163) and
      TD children (n=12). INTERVENTIONS: Standard clinical care at each center. MAIN
      OUTCOME MEASURES: The Dynamic Motor Control Index During Walking (walk-DMC) was
      computed from electromyographic data during gait using muscle synergy analysis.
      Regression analysis was used to evaluate whether pretreatment walking speed or
      kinematics, muscle synergies, treatment group, prior treatment, or age were
      associated with posttreatment changes in gait at both clinical centers. RESULTS:
      Walk-DMC was significantly associated with changes in speed and kinematics after
      treatment with similar regression models at both centers. Children with less
      impaired motor control were more likely to have improvements in walking speed and
      gait kinematics after treatment, independent of treatment group. CONCLUSIONS:
      Dynamic motor control evaluated with synergy analysis was associated with changes
      in gait after treatment at both centers, despite differences in treatments and
      clinical protocols. This study further supports the finding that walk-DMC
      provides additional information, not captured in traditional gait analysis, that
      may be useful for treatment planning.

PMID- 29649452
TI  - Serum secretory phospholipase A2 group IB correlates with the severity of
      membranous nephropathy.
AB  - BACKGROUND: Serum secretory phospholipase A2 group IB (sPLA2-IB) is involved in
      the pathological processes of membranous nephropathy (MN). To date, there is no
      large-scale study validating the usefulness of circulating sPLA2-IB in the follow
      up of patients with MN. This study investigated the role of circulating sPLA2-IB
      in the evaluation of severity of MN. METHODS: A total of 158 patients with
      primary membranous nephropathy (pMN), 34 with secondary membranous nephropathy
      (sMN) and 53 healthy controls were enrolled. Histological staging was made for
      all MN patients. 36 of the pMN patients accepted immunosuppressive therapy and 11
      sMN patients who received treatment of primary disease were followed up for 6
      months. Serum group IB secretory phospholipase A2 (sPLA2-IB), M-type
      phospholipase A2 receptor antibody (PLA2R-Ab), blood urea nitrogen, creatinine,
      total protein, albumin, cholesterol, triglyceride and 24-hour urine protein were
      measured at the time of diagnosis. SPLA2-IB and 24-hour urine protein were
      measured at the end of follow-up. RESULTS: Circulating sPLA2-IB levels were
      significantly higher in pMN and sMN patients compared to controls and negatively
      correlated with TP and albumin, whereas positively correlated with 24-hour urine
      protein. PLA2-IB was found increased with the severity of proteinuria when
      divided MN patiens into three groups according to degree of proteinuria. Through
      the 6-month follow-up, sPLA2-IB and 24 h-urine protein levels were found
      significantly decreased when patients with pMN or sMN reached remission. By ROC
      analysis, PLA2R-Ab was demonstrated to be most significant in the differential
      diagnosis of pMN and sMN compared with 24-hour urinary protein and serum sPLA2
      IB. CONCLUSION: Despite the limited significance to differentiate pMN from sMN,
      sPLA2-IB was correlated with the level of proteinuria in MN patients suggesting
      to be a potential biomarker for monitoring disease severity and therapeutic
      effects of both pMN and sMN.

PMID- 29649453
TI  - Potential role of "omics" technique in prenatal diagnosis of congenital heart
      defects.
AB  - Congenital heart defect (CHD) is one of the most common birth defects and is the
      leading cause of neonatal death. Currently, there are no biomarkers available for
      prenatal diagnosis of CHD. Clinical strategies to diagnose CHD mostly depend on
      fetal echocardiography. Recent advances in "omics" techniques have opened up new
      possibilities for biomarker discoveries. In this review, we discuss recent
      advances in prenatal detection of CHD using biomarkers obtained by "omics"
      approaches, including genomics, proteomics, metabolomics, and others. There is
      great potential in obtaining various kinds of parameters using "omics" studies to
      facilitate early and accurate diagnosis of CHD.

PMID- 29649454
TI  - Association between SCN1A and SCN2A mutations and clinical/EEG features in
      Chinese patients from epilepsy or severe seizures.
AB  - BACKGROUND: We investigated the association between SCN1A and SCN2A mutations and
      clinical phenotype and electroencephalography (EEG) features. METHODS: In this
      study, 48 patients suffered from epilepsy or severe seizures with SCN1A and SCN2A
      mutations were recruited. Medical data and molecular diagnosis were analyzed.
      RESULTS: A total of 47 mutations were identified, including 33 novel mutations.
      The onset of most epilepsy caused by SCN1A mutations (1-6 m) was later than that
      of SCN2A mutations (neonatal). SCN1A mutations included truncating mutations and
      missense mutations occurred in the crucial region were associated with more
      severe phenotypes and developmental delay (85.7%, P = 0.020). De novo mutations
      or truncating mutations of SCN2A mutations are mainly associated with severe
      phenotypes. The proportion of initial abnormal EEG of SCN2A mutation was higher
      than that of SCN1A mutation (54.2%, 100%). Patients with SCN1A mutations showed
      more focal epileptiform discharges (69.2%), while patients with SCN2A mutations
      had more multifocal epileptiform discharges (53.8%). Sodium channel blockers were
      less effective for patients with SCN1A mutations and SCN2A mutations with early
      seizures onset. CONCLUSIONS: Our study expanded the mutation spectrum of the
      SCN1A and SCN2A, and led to a better understanding of the similarities and
      difference in the genetic and clinical features between the two genes.

PMID- 29649455
TI  - Serum Toll-like receptor 4: A novel and promising biomarker for identification of
      aortic aneurysmal diseases.
AB  - BACKGROUND: Immune inflammation appears to play a role in aortic aneurysm (AA)
      pathology. Toll-like receptor 4 (TLR4) has been proved to involve in immune
      inflammatory diseases. However, the relationship between serum TLR4 and AA is
      still unclear. METHODS: The study included 282 AA patients and 287 controls. The
      clinical test related information was collected in medical records. The levels of
      serum TLR4 were measured by enzyme-linked immunosorbent assay. RESULTS: Serum
      TLR4 levels were significantly higher in case groups and could be influenced by
      age, smoking, hypertension, diabetes and hyperlipidemia. Serum TLR4 was
      positively correlated with circulating CRP, Hcy, D-dimer, Fg and Cys-c in AA
      patients, even after adjusting the possible influencing factors. The optimal cut
      off value of TLR4 was 13.64 ng/ml for discriminating AA, and the screening
      accuracy was higher for those who were males (sensitivity of 63.5% and
      specificity of 68.6%), smokers (sensitivity of 63.5% and specificity of 82.7%)
      and hyperlipidemia (sensitivity of 59.1% and specificity of 81.2%). Multiple
      logistic analyses showed that serum TLR4 was significantly correlated with AA
      risk (OR = 1.119, 95% CI = 1.077-1.162, p < 0.001) and subjects with high TLR4
      levels (>13.64 ng/ml) were more likely to have AA (OR = 4.225, 95% CI = 2.477
      7.206, p < 0.001). CONCLUSIONS: Serum TLR4 was closely related to AA and
      associated with some AA-related circulating markers. Serum TLR4 could be a novel
      and promising biomarker with important diagnostic and predictive value in the
      identification of aortic aneurysmal diseases.

PMID- 29649457
TI  - Sudden Creatine Kinase Elevation When an Athlete Starts Boxing: Looking Deeper
      Prior to Knocking the Statin Out.

PMID- 29649458
TI  - Estimating Time Physicians and Other Health Care Workers Spend with Patients in
      an Intensive Care Unit Using a Sensor Network.
AB  - BACKGROUND: Time and motion studies have been used to investigate how much time
      various health care professionals spend with patients as opposed to performing
      other tasks. However, the majority of such studies are done in outpatient
      settings, and rely on surveys (which are subject to recall bias) or human
      observers (which are subject to observation bias). Our goal was to accurately
      measure the time physicians, nurses, and critical support staff in a medical
      intensive care unit spend in direct patient contact, using a novel method that
      does not rely on self-report or human observers. METHODS: We used a network of
      stationary and wearable mote-based sensors to electronically record location and
      contacts among health care workers and patients under their care in a 20-bed
      intensive care unit for a 10-day period covering both day and night shifts.
      Location and contact data were used to classify the type of task being performed
      by health care workers. RESULTS: For physicians, 14.73% (17.96%) of their time in
      the unit during the day shift (night shift) was spent in patient rooms, compared
      with 40.63% (30.09%) spent in the physician work room; the remaining 44.64%
      (51.95%) of their time was spent elsewhere. For nurses, 32.97% (32.85%) of their
      time on unit was spent in patient rooms, with an additional 11.34% (11.79%) spent
      just outside patient rooms. They spent 11.58% (13.16%) of their time at the
      nurses' station and 23.89% (24.34%) elsewhere in the unit. From a patient's
      perspective, we found that care times, defined as time with at least one health
      care worker of a designated type in their intensive care unit room, were
      distributed as follows: 13.11% (9.90%) with physicians, 86.14% (88.15%) with
      nurses, and 8.14% (7.52%) with critical support staff (eg, respiratory
      therapists, pharmacists). CONCLUSIONS: Physicians, nurses, and critical support
      staff spend very little of their time in direct patient contact in an intensive
      care unit setting, similar to reported observations in both outpatient and
      inpatient settings. Not surprisingly, nurses spend far more time with patients
      than physicians. Additionally, physicians spend more than twice as much time in
      the physician work room (where electronic medical record review and documentation
      occurs) than the time they spend with all of their patients combined.

PMID- 29649459
TI  - Breaking Away: Superior Mesenteric Artery Embolus.

PMID- 29649456
TI  - Prognostic value of pretreatment plasma D-dimer levels in patients with diffuse
      large B cell lymphoma (DLBCL).
AB  - BACKGROUND: We assessed the prognostic significance of D-dimer in patients of
      diffuse large B cell lymphoma (DLBCL). METHODS: We performed a retrospective
      study including 254 patients who were newly diagnosed DLBCL. X-tile was used to
      generate a cutoff value for D-dimer. Both univariate screen by Cox proportional
      hazard model and multivariable analysis by Cox regression model were used to
      assess the impact of pretreatment D-dimer levels on the overall survival (OS).
      RESULT: According to X-tile, the optimal cut-off value of D-dimer for prediction
      of survival was set as 1.6 MUg/mL, and a D-dimer level >= 1.6 MUg/mL was
      significantly associated with poor overall survival (OS) (OS: 31.7 vs. 79.1%, P <
      0.001). In multivariable analysis, it was found that a higher D-dimer level was
      an independent predictor for worse OS (Hazard ratio (HR): 3.594 95% Confidence
      interval (CI): 2.296-5.267, P < 0.001). In subgroup analysis of International
      Prognostic Index (IPI), survival of low-risk and intermediate-risk group with a D
      dimer level >= 1.6 MUg/mL were both similar to that of the high-risk group (OS:
      31.6 vs. 36.5%, P = 0.957; OS: 38.0 vs. 36.5%, P = 0.758). In addition, among
      patients treated with surgery, those with higher D-dimer had substantially worse
      survival than that with lower D-dimer (OS: 27.0 vs. 84.5%, P < 0.001).
      CONCLUSION: Pretreatment D-dimer is a simple but effective predictor of survival
      among patients with DLBCL.

PMID- 29649460
TI  - Learning to De-Adopt Ineffective Healthcare Practices.

PMID- 29649461
TI  - The Simplest Explanation: Pancytopenia.

PMID- 29649462
TI  - The Rusty Ring Sign Streamlining Flat Lesion Detection in Subtle Melanosis Coli.

PMID- 29649463
TI  - Common Hepatic Duct Stricture Due to Surgical Clip.

PMID- 29649464
TI  - Choledochoduodenal Fistula Secondary to Ulcer Disease Presenting With
      Gastrointestinal Bleeding.

PMID- 29649465
TI  - Therapeutic time window and regulation of autophagy by mild hypothermia after
      intracerebral hemorrhage in rats.
AB  - Although recent studies have shown that mild hypothermia has neuroprotective
      effects on intracerebral hemorrhage (ICH), the therapeutic time window of the
      therapy and the role of autophagy as a potential neuroprotective mechanism remain
      unclear. This study was aimed to investigate the appropriate time window of mild
      hypothermia and the regulation of autophagy during the treatment in a rat model
      of autologous blood-injected ICH injury. The rats were divided into Sham,
      normothermic (NT) and hypothermic (HT) groups. HT groups received mild
      hypothermia (33  degrees C-35  degrees C) for 48 h starting from 3 h (HT3), 6 h
      (HT6), and 12 h (HT12) respectively after ICH. The neurological function, brain
      edema, blood brain barrier (BBB) permeability and volume of tissue loss were
      tested. The expression of metrix metalloproteinase 9 (MMP-9) and tight junction
      (TJ) protein including Occludin and Claudin-5 around the hematoma were detected
      by Western blot. Moreover, autophagy after ICH was detected by the ratio of LC3B
      II/I, and the expression of Beclin-1 and p62, while apoptosis was evaluated by
      terminal deoxynucleotidyl transferase-mediated dURP nick end labelling (TUNEL)
      staining and expression of Bcl-2, Bim, cleaved Caspase-3. Compared with NT group,
      neurological deficit, brain edema and BBB permeability were attenuated in HT6 and
      HT12 groups, but not in HT3 group, while volume of tissue loss was reduced only
      in HT12 group. The expression of MMP-9 and the degradation of Occludin and
      Claudin-5 were suppressed only in HT6 and HT12 groups, especially in the latter
      one. Moreover, neuronal autophagy and apoptosis induced by ICH were downregulated
      in HT12 group. The results suggested that mild hypothermia initiated at 6 h or 12
      h post-injury was neuroprotective in ICH model of rats, especially at 12 h post
      injury, via suppression of autophagy upregulated by ICH.

PMID- 29649466
TI  - Expression of vesicular glutamate transporters in transient receptor potential
      ankyrin 1 (TRPA1)-positive neurons in the rat trigeminal ganglion.
AB  - Transient receptor potential ankyrin 1 (TRPA1), a cold receptor in sensory
      neurons activated by a variety of stimuli, is implicated in nociception and
      mechanotransduction. To help understand the vesicular glutamate transporter
      (VGLUT)-mediated glutamate signaling in TRPA1-immunopositive (+) neurons, we
      examined the expression of VGLUT1 and VGLUT2 in the TRPA1+ neurons in the male
      rat trigeminal ganglion (n = 19) under normal conditions and following
      experimental inflammation in the vibrissal pad by light microscopic
      immunohistochemistry (n = 11), western blot (n = 8), and quantitative analysis.
      One half (50.8%, 250/492) of the TRPA1+ neurons expressed VGLUT2, and a small
      fraction (8.3%, 57/683) also expressed VGLUT1. The majority of the VGLUT2
      expressing TRPA1+ (VGLUT2+/TRPA1+) neurons coexpressed the markers of peptidergic
      and non-peptidergic neurons, CGRP, IB4, and TRPV1 but not the markers of neurons
      with myelinated fibers, NF200 and parvalbumin. In contrast, most VGLUT1+/TRPA1+
      neurons coexpressed NF200 and parvalbumin but rarely expressed CGRP, IB4, or
      TRPV1. Following experimental inflammation, the fraction of VGLUT2+ (experimental
      vs. control: 34.7% vs. 22.3%), TRPA1+ (39.3% vs. 25.3%), and VGLUT2+/TRPA1+
      (60.7% vs. 49.7%) neurons and the protein levels for TRPA1 and VGLUT2 increased
      significantly, compared to control, whereas the fraction of VGLUT1+ and
      VGLUT1+/TRPA1+ neurons and the protein level for VGLUT1 remained unchanged. These
      findings suggest that both VGLUT1 and VGLUT2 are involved in the glutamate
      signaling in TRPA1+ neurons under normal conditions in the male rats, and raise a
      possibility that VGLUT2 may play a role in the TRPA1-induced hypersensitivity
      following inflammation.

PMID- 29649467
TI  - Monosodium glutamate ingestion during the development period reduces aggression
      mediated by the vagus nerve in a rat model of attention deficit-hyperactivity
      disorder.
AB  - We used an umami substance, monosodium glutamate (MSG), as a simple stimulant to
      clarify the mechanism of the formation of emotional behavior. A 60 mM MSG
      solution was fed to spontaneously hypertensive rats (SHR), used as a model of
      attention-deficit hyperactivity disorder, from postnatal day 25 for 5 weeks kept
      in isolation. Emotional behaviors (anxiety and aggression) were then assessed by
      the open-field test, cylinder test and social interaction test. MSG ingestion
      during the developmental period resulted in a significant reduction in aggressive
      behavior but had few effects on anxiety-like behavior. Several experiments were
      performed to identify the reason for the reduced aggression with MSG intake.
      Blood pressure in the MSG-treated SHR was comparable to that of the controls
      during development. Argyrophil III staining to detect the very early phase of
      neuronal damage revealed no evidence of injury by MSG in aggression-related brain
      areas. Assessment of plasma amino acids revealed that glutamate levels remained
      constant (~80 MUM) with MSG ingestion, except for a transient increase after
      fasting (~700 MUM). However, lactate dehydrogenase assay in an in vitro blood
      brain barrier model showed that cell toxicity was not induced by indirect MSG
      application even at 700 MUM, confirming that MSG ingestion caused minimal
      neuronal damage. Finally, vagotomy at the sub-diaphragmatic level before MSG
      ingestion blocked its effect on aggressive behavior in the isolated SHR. The data
      suggest that MSG ingestion during the developmental period can reduce aggressive
      behavior in an attention deficit-hyperactivity disorder model rat, mediated by
      gut-brain interaction.

PMID- 29649468
TI  - Probing the Amorphous State of Pharmaceutical Compounds Within Mesoporous
      Material Using Pair Distribution Function Analysis.
AB  - Pharmaceutical compounds with poor solubility are loaded within mesoporous
      materials to understand the effect of mesoscale confinement on their dissolution
      behavior. Structural and calorimetric characterization is combined with atomic
      pair distribution function analysis probing the interactions between the silica
      surface and the loaded amorphous compound. While different degrees of amorphism
      are not identifiable from X-ray diffraction data or calorimetric techniques, the
      atomic pair distribution function analysis can help identify local ordering of
      the drug molecules. Together with a list of drug descriptors such as
      crystallization properties, molecular size, and glass transition temperature, the
      behavior of encapsulated compounds and their release kinetics may be
      rationalized. Dissolution experiments confirm that different release rates can be
      achieved with small differences in mesopore design, such as the presence of
      micropores in Santa Barbara Amorphous-15 and loading amount.

PMID- 29649470
TI  - Factors Influencing the Retention of Organic Solvents in Products Freeze-Dried
      From Co-Solvent Systems.
AB  - Controlling residual solvent levels is a major concern in pharmaceutical freeze
      drying from co-solvent systems. This review provides an overview of the factors
      influencing this process and estimates their potential to reduce residual
      solvents in freeze-dried products. Decreased solvent contents are potentially
      correlated with the lower solid content, complete excipient crystallization,
      higher water solubility, and smaller molecular sizes of the solvent. Although no
      general rule can be derived for the selection of appropriate freezing conditions,
      the freezing stage appears to play a major role in subsequent volatile retention.
      In contrast, diverse secondary drying conditions do not appear to impact the
      amount of solvent retained in lyophilisates, and modification of this stage is
      thus not assumed to be expedient. Co-solvents are strongly entrapped in an
      amorphous product matrix as soon as the local moisture content decreases below a
      certain level. Thus, the moisture content in the dried product layer adjacent to
      the sublimation interface might be a key factor. Therefore, extension of the high
      moisture content period during the primary drying phase as well as a
      postlyophilization humidification of the dried products are presumably promising
      approaches to promote solvent release.

PMID- 29649469
TI  - Phosphatidylserine Is Not Just a Cleanup Crew but Also a Well-Meaning Teacher.
AB  - Phosphatidylserine (PS) exposure during apoptosis leads to silent clearance of
      cells without adverse immune reactions to self-proteins. Given the biological
      functions of PS in cellular cleanup and global immunosuppression, we hypothesized
      that administration of PS-protein complexes would reduce immunogenicity. Here, we
      report that exposing Pompe disease mice to acid alpha glucosidase (rhGAA) with PS
      or immunosuppressant dexamethasone resulted in lower anti-rhGAA antibodies than
      in animals receiving rhGAA alone. However, upon rechallenge with rhGAA, only PS
      rhGAA pre-exposed mice displayed a durable hyporesponsiveness even after PS
      administration was ceased. Thus, pre-exposure of antigens administered together
      with PS were not silently cleared, but the immune system acquired memory about
      the antigen that averted mounting of a response during rechallenge. In hemophilia
      A mice, PS hyporesponsiveness toward Factor VIII was reversed by administration
      of function-blocking antibody against the PS receptor T-cell immunoglobulin and
      mucin 4, implicating this receptor in PS's effect. Moreover, pre-exposure of
      myelin oligodendrocyte glycoprotein peptide with PS delayed the onset and reduced
      the severity of experimental autoimmune encephalomyelitis. These observations
      suggest that PS's function in apoptosis is not limited to silent antigen
      clearance without immune responses toward self-proteins but shows that PS reduces
      immune response during rechallenge to several antigens that also involves
      initiation of antigen tolerance.

PMID- 29649471
TI  - Principal coordinate analysis assisted chromatographic analysis of bacterial cell
      wall collection: A robust classification approach.
AB  - In the present work, Principal coordinate analysis (PCoA) is introduced to
      develop a robust model to classify the chromatographic data sets of peptidoglycan
      sample. PcoA captures the heterogeneity present in the data sets by using the
      dissimilarity matrix as input. Thus, in principle, it can even capture the subtle
      differences in the bacterial peptidoglycan composition and can provide a more
      robust and fast approach for classifying the bacterial collection and identifying
      the novel cell wall targets for further biological and clinical studies. The
      utility of the proposed approach is successfully demonstrated by analysing the
      two different kind of bacterial collections. The first set comprised of
      peptidoglycan sample belonging to different subclasses of Alphaproteobacteria.
      Whereas, the second set that is relatively more intricate for the chemometric
      analysis consist of different wild type Vibrio Cholerae and its mutants having
      subtle differences in their peptidoglycan composition. The present work clearly
      proposes a useful approach that can classify the chromatographic data sets of
      chromatographic peptidoglycan samples having subtle differences. Furthermore,
      present work clearly suggest that PCoA can be a method of choice in any data
      analysis workflow.

PMID- 29649472
TI  - Accurate RNA 5-methylcytosine site prediction based on heuristic physical
      chemical properties reduction and classifier ensemble.
AB  - RNA 5-methylcytosine (m5C) is an important post-transcriptional modification that
      plays an indispensable role in biological processes. The accurate identification
      of m5C sites from primary RNA sequences is especially useful for deeply
      understanding the mechanisms and functions of m5C. Due to the difficulty and
      expensive costs of identifying m5C sites with wet-lab techniques, developing fast
      and accurate machine-learning-based prediction methods is urgently needed. In
      this study, we proposed a new m5C site predictor, called M5C-HPCR, by introducing
      a novel heuristic nucleotide physicochemical property reduction (HPCR) algorithm
      and classifier ensemble. HPCR extracts multiple reducts of physical-chemical
      properties for encoding discriminative features, while the classifier ensemble is
      applied to integrate multiple base predictors, each of which is trained based on
      a separate reduct of the physical-chemical properties obtained from HPCR.
      Rigorous jackknife tests on two benchmark datasets demonstrate that M5C-HPCR
      outperforms state-of-the-art m5C site predictors, with the highest values of MCC
      (0.859) and AUC (0.962). We also implemented the webserver of M5C-HPCR, which is
      freely available at http://cslab.just.edu.cn:8080/M5C-HPCR/.

PMID- 29649473
TI  - Development of Quenching-qPCR (Q-Q) assay for measuring absolute intracellular
      cleavage efficiency of ribozyme.
AB  - Ribozyme (Rz) is a very attractive RNA molecule in metabolic engineering and
      synthetic biology fields where RNA processing is required as a control unit or
      ON/OFF signal for its cleavage reaction. In order to use Rz for such RNA
      processing, Rz must have highly active and specific catalytic activity. However,
      current methods for assessing the intracellular activity of Rz have limitations
      such as difficulty in handling and inaccuracies in the evaluation of correct
      cleavage activity. In this paper, we proposed a simple method to accurately
      measure the "intracellular cleavage efficiency" of Rz. This method deactivates
      unwanted activity of Rz which may consistently occur after cell lysis using DNA
      quenching method, and calculates the cleavage efficiency by analyzing the cleaved
      fraction of mRNA by Rz from the total amount of mRNA containing Rz via
      quantitative real-time PCR (qPCR). The proposed method was applied to measure
      "intracellular cleavage efficiency" of sTRSV, a representative Rz, and its
      mutant, and their intracellular cleavage efficiencies were calculated as 89% and
      93%, respectively.

PMID- 29649474
TI  - Mucin and carbon nanotube-based biosensor for detection of glucose in human
      plasma.
AB  - This work reports an amperometric enzyme-electrode prepared with glucose oxidase,
      which have been immobilized by a cross-linking step with glutaraldehyde in a
      mixture containing albumin and a novel carbon nanotubes-mucin composite (CNT
      muc). The obtained hydrogel matrix was trapped between two polycarbonate
      membranes and then fixed at the surface of a Pt working electrode. The developed
      biosensor was optimized by evaluating different compositions and the analytical
      properties of an enzymatic matrix with CNT-muc. Then, the performance of the
      resulting enzymatic matrix was evaluated for direct glucose quantification in
      human blood plasma. The novel CNT-muc composite provided a sensitivity of 0.44 +/
      0.01 mA M-1 and a response time of 28 +/- 2 s. These values were respectively
      20% higher and 40% shorter than those obtained with a sandwich-type biosensor
      prepared without CNT. Additionally, CNT-muc based biosensor exhibited more than 3
      orders of magnitude of linear dynamic calibration range and a detection limit of
      3 MUM. The short-term and long-term stabilities of the biosensors were also
      examined and excellent results were obtained through successive experiments
      performed within the first 60 days from their preparation. Finally, the storage
      stability was remarkable during the first 300 days.

PMID- 29649475
TI  - Use of DNA aptamer for sandwich type detection of Listeria monocytogenes.
AB  - A single stranded (ss) DNA aptamer, specific to members of Listeria genus, was
      used to develop a two-site binding sandwich assay for capture and detection of L.
      monocytogenes. Antibody-immobilized immunomagnetic beads were used to capture L.
      monocytogenes, followed by their exposure to the aptamer detector. Detection was
      achieved by amplification of cell-bound aptamers by qPCR. The lower limit of
      detection for the combined assay was 2.5 CFU L. monocytogenes in 500 MUl buffer.
      This is juxtaposed to a detection limit of 2.4 log10 CFU in 500 MUl buffer for
      immunomagnetic separation coupled with qPCR detection of L. monocytogenes
      targeting the hly gene. When applied to turkey deli meat, subjected to 24 h of
      non-selective enrichment, the two-site binding sandwich assay showed positive
      results at initial inoculum levels of 1-2 log10 CFU per 25 g sample. Because of
      its lower limit of detection, the assay reported here could be useful for
      detection of L. monocytogenes in foods and environmental samples.

PMID- 29649476
TI  - H2A.Z-containing nucleosomes are evicted to activate AtMYB44 transcription in
      response to salt stress.
AB  - Transcripts of the Arabidopsis transcription factor gene, AtMYB44, accumulate
      rapidly to mediate a tolerance mechanism in response to salt stress. The AtMYB44
      promoter is activated by salt stress, as illustrated in AtMYB44pro::GUS
      transgenic plants. Chromatin immunoprecipitation (ChIP) assays revealed that RNA
      polymerases were enriched on the AtMYB44 gene, especially on TSS-proximal
      regions, and nucleosome density was markedly reduced in the AtMYB44 gene-body
      region in response to salt stress. In addition, H2A.Z occupation was
      significantly decreased at the AtMYB44 promoter, transcription start site (TSS),
      and gene-body regions. Histone modifications including histone H3 lysine 4
      trimethylation (H3K4me3) and histone H3 and H4 acetylation (H3ac and H4ac) were
      not affected under the same stress conditions. We found a decrease in the number
      of AtMYB44 proteins bound to their own gene promoters in response to salt stress.
      These results suggest that salt stress induces the eviction of H2A.Z-containing
      nucleosomes from the AtMYB44 promoter region, which may weaken its affinity for
      binding AtMYB44 protein that acts as a repressor for AtMYB44 gene transcription
      under salt stress-free conditions.

PMID- 29649477
TI  - Involvement of prostatic interstitial cells of Cajal in inflammatory cytokines
      elicited catecholamines production: Implications for the pathophysiology of
      chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).
AB  - In a previous work using guinea pig prostate, we have identified a novel
      interstitial cells of Cajal (ICCs) which possess close contacts between
      sympathetic nerve bundles and smooth muscle cells. The ability of prostatic ICCs
      in mediating excitatory neural inputs was therefore studied using isolated murine
      prostate ICCs by collagenase digestion combined with FACS method. RT-PCR and
      Western blotting analyses revealed that prostatic ICCs under a quiescent state
      expressed abundantly the rate-limiting enzymes essential for catecholamine
      synthesis. Moreover, distinct proinflammatory cytokines (e.g. IL-1beta, IL-8,
      ICAM-1 and TNF-alpha) could significantly stimulate the expression levels of the
      rate-limiting enzymes of catecholamine production in prostate ICCs.
      Mechanistically, the above-mentioned stimulatory effects of proinflammatory
      cytokines appeared to be mediated via activation of NF-kappaB, HIF-1alpha and
      HDACs signaling pathways. Considering that prostatic catecholamine overactivity
      serves as an essential etiology of pelvic pain by indirectly stimulating the
      smooth muscle cell proliferation, or by directly causing muscular spasm, our
      results collectively suggest that targeting the NF-kappaB, HIF-1alpha and HDACs
      pathways in prostate ICCs be considered as a new strategy for treatment of
      chronic pelvic pain syndrome (CPPS) induced by chronic prostatitis (CP). Overall,
      the current study should shed novel light on the biology of this unique prostate
      ICCs.

PMID- 29649478
TI  - Autophagy alteration prevents primary cilium disassembly in RPE1 cells.
AB  - Primary cilium is a microtubule structure that emanates from the surface of most
      human cells. Primary cilia assemble during the resting stage (G0 phase) and
      disassemble with cell cycle progression. Defects associated with the control of
      the assembly or disassembly of the primary cilium have been implicated in various
      human diseases, including ciliopathy and cancer. Although studies have suggested
      the interplay between activation of autophagy and ciliogenesis, any direct
      mechanism between autophagy abatement and disassembly of primary cilium remains
      elusive. In this study, we found that the gradual abatement in autophagy during
      serum-restimulation was a dynamic process and significantly correlated with the
      disassembly of primary cilium in human retinal pigmented epithelial (RPE1) cells.
      Although autophagy activity was gradually decreased during serum-restimulation,
      the alteration in autophagy under the same condition prevented the disassembly of
      the primary cilium. Autophagy inhibitors such as chloroquine, U18666A and 3
      methyladenine (3-MA) retained both the number of ciliated cells and cilium
      length. In contrast, rapamycin treatment during serum-restimulation maintained
      the number of ciliated cells with shortened cilia. Taken together, alteration in
      autophagy during serum-restimulation prevent the disassembly of the primary
      cilium, and autophagy modulators may serve as useful compounds for studying
      mechanistic details related to the disassembly of the primary cilium and
      ciliopathy.

PMID- 29649479
TI  - A spherical aberration-free microscopy system for live brain imaging.
AB  - The high-resolution in vivo imaging of mouse brain for quantitative analysis of
      fine structures, such as dendritic spines, requires objectives with high
      numerical apertures (NAs) and long working distances (WDs). However, this imaging
      approach is often hampered by spherical aberration (SA) that results from the
      mismatch of refractive indices in the optical path and becomes more severe with
      increasing depth of target from the brain surface. Whereas a revolving objective
      correction collar has been designed to compensate SA, its adjustment requires
      manual operation and is inevitably accompanied by considerable focal shift,
      making it difficult to acquire the best image of a given fluorescent object. To
      solve the problems, we have created an objective-attached device and formulated a
      fast iterative algorithm for the realization of an automatic SA compensation
      system. The device coordinates the collar rotation and the Z-position of an
      objective, enabling correction collar adjustment while stably focusing on a
      target. The algorithm provides the best adjustment on the basis of the calculated
      contrast of acquired images. Together, they enable the system to compensate SA at
      a given depth. As proof of concept, we applied the SA compensation system to in
      vivo two-photon imaging with a 25 * water-immersion objective (NA, 1.05; WD, 2
      mm). It effectively reduced SA regardless of location, allowing quantitative and
      reproducible analysis of fine structures of YFP-labeled neurons in the mouse
      cerebral cortical layers. Interestingly, although the cortical structure was
      optically heterogeneous along the z-axis, the refractive index of each layer
      could be assessed on the basis of the compensation degree. It was also possible
      to make fully corrected three-dimensional reconstructions of YFP-labeled neurons
      in live brain samples. Our SA compensation system, called Deep-C, is expected to
      bring out the best in all correction-collar-equipped objectives for imaging deep
      regions of heterogeneous tissues.

PMID- 29649480
TI  - High glucose downregulates the effects of autophagy on osteoclastogenesis via the
      AMPK/mTOR/ULK1 pathway.
AB  - Diabetes is a chronic disease that disrupts the balance between bone formation
      and bone desorption, which can lead to osteoporosis, increasing the risk of
      fracture. However, compared with osteoblasts, the biological effects of
      hyperglycemia on osteoclastogenesis remain to be elucidated. Therefore, we
      investigated the impact of glucose at different concentrations (5.5, 10.5, 15.5,
      20.5, 25.5, and 30.5 mM) on osteoclastogenesis using RAW264.7 cells. Cell
      proliferation was measured with the cell counting kit-8 assay, and
      osteoclastogenesis was detected with tartrate-resistant acid phosphatase staining
      and bone resorption assays, as well as protein cathepsin K expression. Compound
      C, the AMP-activated protein kinase (AMPK) pathway inhibitor, was used to examine
      the relationship between the AMPK/mTOR/ULK1 signaling pathway and autophagy in
      osteoclasts. Autophagy was evaluated with transmission electron microscopy and
      immunofluorescence microscopy and associated proteins were detected with western
      blotting. The pharmacological autophagic reagents bafilomycin A1, 3
      methyladenine, and rapamycin were used to determine the effect of autophagy on
      osteoclastogenesis. Our results showed that glucose negatively affected
      osteoclast formation and function but did not affect the proliferation of
      RAW264.7 cells. Suppression of the AMPK/mTOR/ULK1 signaling axis decreased
      autophagy in glucose-mediated osteoclast. Furthermore, High levels of glucose
      decreased autophagy level in osteoclasts. Additionally, interfering with
      autophagy affected osteoclast formation and function. These findings clarify the
      mechanisms underlying the effects of glucose-mediated osteoclastogenesis and will
      help identify novel therapeutic strategies for the protection of skeletal health
      in diabetic osteoporosis.

PMID- 29649482
TI  - Phylogeny and evolution of the cholesterol transporter NPC1 in insects.
AB  - Sterols are essential nutrients for eukaryotes. Insects are obligate sterol
      auxotrophs and must acquire this key nutrient from their diets. The digestive
      tract is the organ for absorbing nutrients as well as sterols from food. In mice,
      the Niemann-Pick type C1 Like 1 (NPC1L1) gene is highly expressed in the
      intestine and is critical for cholesterol absorption. In contrast, the molecular
      mechanisms for the absorption of dietary sterols in insects have not been well
      studied. We annotated NPC1 genes in 39 insects from 10 orders using available
      genomic and transcriptomic information and inferred phylogenetic relationships.
      Insect NPC1 genes were grouped into two sister-clades, NPC1a and NPC1b,
      suggesting a likely duplication in the ancestor of insects. The former exhibited
      weaker gut-biased expression or a complete lack of tissue-biased expression,
      depending on the species, while the latter was highly enriched in the gut of
      three lepidopteran species. This result is similar to previous findings in
      Drosophila melanogaster. In insects, NPC1a accumulated non-synonymous
      substitutions at a lower rate than NPC1b. This pattern was consistent across
      orders, indicating that NPC1a evolved under stronger molecular constraint than
      NPC1b.

PMID- 29649481
TI  - Role of IkappaB kinase beta in regulating the remodeling of the CARMA1-Bcl10
      MALT1 complex.
AB  - The current work investigates the notion that inducible clustering of signaling
      mediators of the IKK pathway is important for platelet activation. Thus, while
      the CARMA1, Bcl10, and MALT1 (CBM) complex is essential for triggering IKK/NF
      kappaB activation upon platelet stimulation, the signals that elicit its
      formation and downstream effector activation remain elusive. We demonstrate
      herein that IKKbeta is involved in membrane fusion, and serves as a critical
      protein kinase required for initial formation and the regulation of the
      CARMA1/MALT1/Bcl10/CBM complex in platelets. We also show that IKKbeta regulates
      these processes via modulation of phosphorylation of Bcl10 and IKKgamma
      polyubiquitination. Collectively, our data demonstrate that IKKbeta regulates
      membrane fusion and the remodeling of the CBM complex formation.

PMID- 29649483
TI  - Redefining reproductive dormancy in Drosophila as a general stress response to
      cold temperatures.
AB  - Organisms regularly encounter unfavorable conditions and the genetic adaptations
      facilitating survival have been of long-standing interest to evolutionary
      biologists. Winter is one particularly stressful condition for insects, during
      which they encounter low temperatures and scarcity of food. Despite dormancy
      being a well-studied adaptation to facilitate overwintering, there is still
      considerable controversy about the distribution of dormancy among natural
      populations and between species in Drosophila. The current definition of dormancy
      as developmental arrest of oogenesis at the previtellogenic stage (stage 7)
      distinguishes dormancy from general stress related block of oogenesis at early
      vitellogenic stages (stages 8 - 9). In an attempt to resolve this, we scrutinized
      reproductive dormancy in D. melanogaster and D. simulans. We show that dormancy
      shows the same hallmarks of arrest of oogenesis at stage 9, as described for
      other stressors and propose a new classification for dormancy. Applying this
      modified classification, we show that both species express dormancy in
      cosmopolitan and African populations, further supporting that dormancy uses an
      ancestral pathway induced by environmental stress. While we found significant
      differences between individuals and the two Drosophila species in their
      sensitivity to cold temperature stress, we also noted that extreme temperature
      stress (8  degrees C) resulted in very strong dormancy incidence, which strongly
      reduced the differences seen at less extreme temperatures. We conclude that
      dormancy in Drosophila should not be considered a special trait, but is better
      understood as a generic stress response occurring at low temperatures.

PMID- 29649484
TI  - Vision and genesis of survival strategies in tsetse flies: A laboratory study.
AB  - Organisms respond to environmental stimuli in ways that optimize survival and
      reproduction. Tsetse fly life-history is characterized by high investment in
      progeny by the pregnant female and low birth rate. This places constraints on
      tsetse populations across the sub-Saharan biotopes they colonize where extreme
      climatic conditions militate against survival. Controlling metabolic rate is
      crucial in biotopes where daily swings in temperature can exceed 20  degrees C.
      Tsetse acquire their nutrient requirements from the blood meal. These diurnal
      flies are otherwise confined for most of their lives to perching sites in the
      shade. At these locations they are simultaneously threatened by vertebrate and
      invertebrate predators. Here we describe behaviours of the East African tsetse
      Glossina pallidipes Austen (Diptera: Glossinidae) that permit it to reduce risk
      daily. Newly-emerged flies remain immobile at emergence in the photophase but
      scotophase-emerging flies walk away within seconds to climb (negative geotaxis)
      vertical substrates to find a perch off the ground. Flies of all ages show the
      ability to fly in almost total darkness (1.10-5 lux) in the scotophase to perch
      on the upper side of horizontally suspended 1 cm diameter bars, simulating
      branches of vegetation, but perch under the same bars during the photophase. This
      underlines the predilection of tsetse for objects with a linear aspect that
      provide a vantage point and shade. Mature G. pallidipes can discriminate between
      horizontally suspended bars of different diameter and shape. Flicker fusion
      frequency values established by optomotor and retinogram recordings reveal a
      higher visual acuity in mature compared to newly-emerged tsetse.

PMID- 29649486
TI  - Identification of the two new, functional actinoporins, CJTOX I and CJTOX II,
      from the deep-sea anemone Cribrinopsis japonica.
AB  - Actinoporins are pore-forming proteins found in sea anemones. Although we now
      have a large collection of data on actinoporins, our knowledge is based heavily
      on those identified in shallow-water anemones. Because the deep sea differs
      considerably from shallow waters in hydrostatic pressures, temperatures, and the
      prey composition, the deep-sea actinoporin may have evolved in unique ways. This
      study, therefore, aimed to obtain new actinoporins in the deep-sea anemone
      Cribrinopis japonica (Actiniaria, Actiniidae). An actinoporin-like sequence was
      identified from the previously established C. japonica RNA-Seq database, and the
      complete length (663 bp) of the deep-sea actinoporin gene, Cjtox I, was obtained.
      In addition, a similar gene, Cjtox II (666 bp), was also identified from RNA of
      actinopharynx. CJTOX I and CJTOX II were similar in their primary structures, but
      CJTOX I lacked one residue in the middle of the protein. There was also a
      difference in the gene expression in live animals, where only Cjtox I was
      expressed in tentacles of C. japonica. In the heterologous expression where BL21
      (DE3) strain was retransformed with the plasmid containing either Cjtox I or
      Cjtox II gene, the supernatants of both cell lysates showed hemolytic activity on
      the equine erythrocytes. Preincubation of the supernatants with sphingomyelin
      caused reduced activity, implying that the CJTOX I and II would target
      sphingomyelin as with other actinoporins. Because of the structures similarity to
      the known actinoporins and the sphingomyelin-inhibitable hemolytic activity, both
      CJTOX I and II were concluded to be new actinoporins, which were identified for
      the first time from a deep-sea anemone.

PMID- 29649485
TI  - Occult globe rupture: diagnostic and treatment challenge.
AB  - Occult globe rupture is a traumatic dehiscence of the sclera at or posterior to
      the rectus muscle insertions without a visible eye wall defect on slit lamp
      examination. Occult scleral ruptures are important because they can be difficult
      to diagnose, but normally require preoperative protection against external
      pressure to reduce risk of herniation of ocular contents through the rupture and
      then urgent surgical repair to restore eye wall structural integrity and achieve
      optimum prognosis. A deeper-than-normal anterior chamber with posteriorly
      retracted plateau iris seen immediately after acute ocular trauma is virtually
      pathognomonic of posterior globe dehiscence. Three additional less specific signs
      are helpful: extensive chemosis that is often hemorrhagic, relative hypotony, and
      vitreous hemorrhage. Although the diagnosis is normally clinical, made by history
      of direct severe ocular trauma and careful anterior-segment slit lamp
      examination, computed tomography and ultrasonography can be helpful when thorough
      slit lamp examination is not possible. Strong suspicion of occult rupture should
      engender surgical exploration. Vitreous hemorrhage, vitreous or retinal
      incarceration, and retinal tears or detachment may necessitate subsequent pars
      plana vitrectomy or other vitreoretinal surgery. When pars plana vitrectomy is
      indicated, special precautions are suggested if watertight closure of the globe
      rupture has not been possible.

PMID- 29649487
TI  - Expression patterns and role of PTEN in rat peripheral nerve development and
      injury.
AB  - Studies have suggested that phosphatase and tensin homolog (PTEN) plays an
      important role in neuroprotection and neuronal regeneration. To better understand
      the potential role of PTEN with respect to peripheral nerve development and
      injury, we investigated the expression pattern of PTEN at different stages of rat
      peripheral nerve development and injury and subsequently assessed the effect of
      pharmacological inhibition of PTEN using bpV(pic) on axonal regeneration in a rat
      sciatic nerve crush injury model. During the early stages of development, PTEN
      exhibits low expression in neuronal cell bodies and axons. From embryonic day (E)
      18.5 and postnatal day (P)5 to adult, PTEN protein becomes more detectable, with
      high expression in the dorsal root ganglia (DRG) and axons. PTEN expression is
      inhibited in peripheral nerves, preceding myelination during neuronal development
      and remyelination after acute nerve injury. Low PTEN expression after nerve
      injury promotes Akt/mammalian target of rapamycin (mTOR) signaling pathway
      activity. In vivo pharmacological inhibition of PTEN using bpV(pic) promoted
      axonal regrowth, increased the number of myelinated nerve fibers, improved
      locomotive recovery and enhanced the amplitude response and nerve conduction
      velocity following stimulation in a rat sciatic nerve crush injury model. Thus,
      we suggest that PTEN may play potential roles in peripheral nerve development and
      regeneration and that inhibition of PTEN expression is beneficial for nerve
      regeneration and functional recovery after peripheral nerve injury.

PMID- 29649488
TI  - Proteomics based identification of differential plasma proteins and changes in
      white matter integrity as markers in early detection of mild cognitive impaired
      subjects at high risk of Alzheimer's disease.
AB  - Mild cognitive impairment (MCI) is an intermediate stage of cognitive decline and
      dementia. The absence of specific diagnostic test for identification of MCI and
      AD. The current study aims to find proteomics based change in plasma proteins and
      diffusion tensor imaging (DTI) based white matter changes in MCI for early
      detection of prodromal Alzheimer's disease. Fifty cases of mild cognitive
      impairment and age matched control between (55-75 yrs) were screened on basis of
      Mini Mental State Examination (MMSE). Two dimensional gel electrophoresis and DTI
      imaging was performed in MCI and age matched control. The MMSE score of MCI were
      in the range of (28 +/- 2-22.6 +/- 1) as compared with healthy control (28 +/-
      2), DTI metrics apparent diffusion coefficient (ADC) and fractional Anisotropy
      (FA) has shown significant changes in fornix, corpus callosum, hippocampus, right
      temporal and right frontal lobe, left frontal lobe, forcep major of MCI subjects
      as compared with controls. The protein expression of keratin type-2 was up
      regulated and albumin was down regulated in MCI subjects as compared with
      control. The data from present study signifies that expression of Keratin type-2
      and albumin along with white matter changes provides early signatures for
      identification of MCI at high risk of Alzheimer's disease.

PMID- 29649489
TI  - Albumin levels and cause-specific mortality in community-dwelling older adults.
AB  - To investigate the association between serum albumin levels and cause-specific
      mortality among community-dwelling older adults. This cohort study was based on
      data obtained from the government-sponsored Annual Geriatric Health Examination
      Program for the older adults in Taipei City between 2006 and 2010. The study
      sample consisted of 77,531 community-dwelling Taipei citizens (>=65 years old).
      Mortality was determined by matching the participants' medical records with
      national death files. Serum albumin levels were categorized into <3.6, 3.6-3.7,
      3.8-3.9, 4.0-4.1, 4.2-4.3, and >=4.4 g/dL. Cox proportional hazards regression
      models were used to evaluate the association between albumin levels and cause
      specific mortality. Spline regression was used to calculate the risk of mortality
      associated with albumin levels, modeled as continuous variables. Community
      dwelling older adults had a mean albumin level of 4.3 g/dL, which significantly
      reduced by age. Compared to albumin levels >=4.4 g/dL, mildly low albumin levels
      (4.2-4.3 g/dL) were associated with an increased mortality risk (hazard ratio
      [HR]: 1.16, 95% confidence interval [CI]: 1.05-1.28 for all-cause mortality), and
      albumin levels <4.2 g/dL were associated with significantly higher rates of all
      cause, cancer, cardiovascular, and respiratory mortalities. In the spline
      regression, the curve of mortality risk was relatively flat at an albumin level
      >=4.4 g/dL, and the mortality risk gradually increased as the albumin level
      declined. Albumin levels >=4.4 g/dL were associated with better survival among
      community-dwelling older adults, and mortality risk increased as the albumin
      level decreased.

PMID- 29649491
TI  - Toxicological characteristics of edible insects in China: A historical review.
AB  - Edible insects are ideal food sources, which contain important nutrients and
      health-promoting compounds. With a rapid development of industrial insect
      farming, insect-derived food is a novel and emerging food industry. Edible
      insects have been traditionally consumed in various communities, while
      continuously gaining relevance in today's society; however, they currently remain
      underutilized. Although there are a large number of literature on edible insects,
      these literature primarily focus on the nutritional value edible insects. The
      toxicity assessment data of edible insects remain incomprehensive, especially for
      the new national standard that is currently in effect; and many data and
      conclusions are not accurately specified/reported. Therefore, we performed a
      literature review and summarized the data on the toxicological assessment of
      edible insects in China. The review first describes the research progress on
      safety toxicological assessment, and then offers references regarding the
      development of 34 edible insect species in China. These data can be a platform
      for the development of future toxicological assessment strategies, which can be
      carried out by a multidisciplinary team, possibly consisting of food engineers,
      agronomists, farmers, and so on, to improve the acceptability of edible insects.

PMID- 29649490
TI  - Aggregate exposure to common fragrance compounds: Comparison of the contribution
      of essential oils and cosmetics using probabilistic methods and the example of
      limonene.
AB  - The knowledge of aggregate exposure to different types of products is paramount
      in the risk assessment. The aim of this study was to compare the relative
      contribution of essential oils compared to cosmetics on the daily dermal exposure
      to limonene, an ubiquitous fragrance compound that can be an allergen depending
      on its degree of oxidation. Aggregate daily exposure to limonene was calculated
      among a panel of French volunteers using both essential oils and cosmetics, for 4
      different specific zones, i.e. face and neck, chest, upper limbs and lower limbs.
      Calculations were made using a probabilistic Monte Carlo method and sensitivity
      analysis. The main strength of this work was the inclusion of essential oils in
      addition to cosmetics in the model. For the first time, the generated data could
      be used to compare the contribution of these two products in dermal exposure.
      Essential oils appear to be significant contributors to exposure to limonene
      particularly for the face. This work is a first step that will permit to
      determine the exposure to other fragrance compounds with sensitizing potential.
      These data will be useful for risk managers to consider the inclusion of
      essential oils in the overall burden of this pathology.

PMID- 29649492
TI  - A cytoskeletal activator and inhibitor are downstream targets of the
      frizzled/starry night planar cell polarity pathway in the Drosophila epidermis.
AB  - The frizzled pathway regulates the planar polarity of epithelial cells. In
      insects this is manifested by the polarity of cuticular structures such as hairs
      (trichomes) and sensory bristles. A variety of evidence has established that this
      is achieved by regulating the subcellular location for activating the
      cytoskeleton in the epithelial cells. How this is accomplished is still poorly
      understood. In the best-studied tissue, the Drosophila pupal wing two important
      cytoskeletal regulators have been identified. One, shavenoid (sha), appears to be
      an activator while the second multiple wing hairs (mwh), appears to be an
      inhibitor. In vitro biochemistry has confirmed that the Multiple Wing Hairs
      protein inhibits the elongation of F-actin chains and surprisingly that it also
      bundles F-actin. These two activities can explain the multifaceted mwh mutant
      phenotype.

PMID- 29649493
TI  - Inonotolides A-C, isopimarane diterpenoid lactones from Inonotus sinensis.
AB  - Three new isopimarane diterpenoid lactones, named inonotolides A-C (1-3), were
      isolated from cultures of the basidiomycete Inonotus sinensis. Their structures
      were elucidated on the basis of extensive spectroscopic studies and the structure
      of inonotolide A (1) was confirmed by single-crystal X-ray crystallographic
      analysis. All compounds were evaluated for their cytotoxicities against five
      human cancer cell lines.

PMID- 29649494
TI  - Cardenolides from the stem bark of Salacia staudtiana.
AB  - Seven new cardenolides, staudtianoside A-F (1-6) and staudtianogenin A (8), were
      isolated along with six known compounds from the stem bark of the Cameroonian
      medicinal plant Salacia staudtiana Loes. ex Fritsch. The structures were
      elucidated by means of ESI-HRMS and NMR spectroscopic methods and by comparison
      with literature data. The relative configurations of the new compounds were
      determined by X-ray diffraction analysis, NOESY correlation and coupling
      constants. We evaluated the antibacterial efficacy of the isolated compounds
      against two commonly dispersed environmental strains of Escherichia coli and
      Bacillus subtilis, as well as against two human pathogenic clinical strains of
      Staphylococcus aureus and Pseudomonas aeruginosa. Compounds 1, 2 and 8 exhibited
      marked antibacterial potencies against the clinically relevant P. aeruginosa that
      were comparable to the standard antibiotics. Compound 2 was also active against
      S. aureus and E. coli. Further, compounds 5 and 8 demonstrated efficacy against
      E. coli as well as B. subtilis. The structure-activity relationship of the tested
      compounds is discussed.

PMID- 29649496
TI  - The evolution of nucleoside analogue antivirals: A review for chemists and non
      chemists. Part 1: Early structural modifications to the nucleoside scaffold.
AB  - This is the first of two invited articles reviewing the development of nucleoside
      analogue antiviral drugs, written for a target audience of virologists and other
      non-chemists, as well as chemists who may not be familiar with the field. Rather
      than providing a simple chronological account, we have examined and attempted to
      explain the thought processes, advances in synthetic chemistry and lessons
      learned from antiviral testing that led to a few molecules being moved forward to
      eventual approval for human therapies, while others were discarded. The present
      paper focuses on early, relatively simplistic changes made to the nucleoside
      scaffold, beginning with modifications of the nucleoside sugars of Ara-C and
      other arabinose-derived nucleoside analogues in the 1960's. A future paper will
      review more recent developments, focusing especially on more complex
      modifications, particularly those involving multiple changes to the nucleoside
      scaffold. We hope that these articles will help virologists and others outside
      the field of medicinal chemistry to understand why certain drugs were
      successfully developed, while the majority of candidate compounds encountered
      barriers due to low-yielding synthetic routes, toxicity or other problems that
      led to their abandonment.

PMID- 29649495
TI  - A Guinea pig cytomegalovirus resistant to the DNA maturation inhibitor BDCRB.
AB  - Herpesvirus DNA packaging is an essential step in virion morphogenesis and an
      important target for antiviral development. The halogenated benzimidazole 2-bromo
      5,6-dichloro-1-beta-d-ribofuranosyl-1H-benzimidazole (BDCRB) was the first
      compound found to selectively disrupt DNA packaging. It has activity against
      human cytomegalovirus as well as guinea pig cytomegalovirus. The latter provides
      a useful small animal model for congenital cytomegalovirus infection. To better
      understand the mechanism by which BDCRB acts, a guinea pig cytomegalovirus
      resistant to BDCRB was derived and characterized. An L406P substitution occurred
      within GP89, a subunit of the complex that cleaves and packages DNA, but transfer
      of this mutation to an otherwise wild type genetic background did not confer
      significant BDCRB resistance. The resistant virus also had a 13.4-kb deletion
      that also appeared to be unrelated to BDCRB-resistance as a virus with a similar
      spontaneous deletion was sensitive to BDCRB. Lastly, the BDCRB-resistant virus
      exhibited a dramatic increase in the number of reiterated terminal repeats at
      both genomic termini. The mechanism that underlies this change in genome
      structure is not known but may relate to the duplication of terminal repeats that
      is associated with DNA cleavage and packaging. A model is presented in which
      BDCRB impairs the ability of terminase to recognize cleavage site sequences, but
      repeat arrays overcome this impairment by presenting terminase with multiple
      opportunities to recognize the correct cleavage site sequences that lie within
      the repeats. Further elucidation of this phenomenon should prove valuable for
      understanding the molecular basis of herpesvirus DNA maturation and the mechanism
      of action of this class of drugs.

PMID- 29649497
TI  - Chrystile asbestos cement and the Grenfell Tower fire.
AB  - On 14 June 2017, a fire broke out at Grenfell Tower: a residential block in North
      Kensington, London, UK. Soon the whole tower was ablaze and it took firefighters
      over 24 h to get the fire under control. Some 71 people were confirmed or
      presumed dead and around 70 injured. Among the many reasons given for the blaze
      none discuss why a Tower Block, constructed in 1974, from materials whose fire
      safety had been checked was recently refurbished with materials considered by
      many to be flammable. The frame of the tower had curtain walls, originally
      finished with 6 infill panels constructed from 4 glass windows and two 3 ply
      composite panels constructed with chrysotile cement. These panels had been fire
      tested and all passed the stringent 1 h fire requirements for insulation and
      spread of flame. They were used on many high rise buildings throughout the UK.
      Additional fire safety in the block was provided by AIB lined fire doors. After
      the UK/EU ban on chrysotile in 1999 the Labour Government enforced the removal of
      all such panels and the fire doors claiming they were a threat to life from the
      asbestos they contained. The tower was refurbished in 2015-2016 when the AIB fire
      doors were replaced by timber doors and the asbestos cement panels were replaced
      with a new cladding. This was almost certainly the cause of the fire. Had the
      original asbestos cement panels remained in place the disastrous fire could not
      have developed.

PMID- 29649499
TI  - The spinal ependymal zone as a source of endogenous repair cells across
      vertebrates.
AB  - Spinal cord injury results in the loss of neurons and axonal connections. In
      mammals, including humans, this loss is permanent, but is repaired in other
      vertebrates, such as salamanders and fishes. Cells in the ependymal niche play a
      pivotal role for the outcome after injury. These cells initiate proliferation and
      generate new neurons of different types in regenerating species, but only glial
      cells, contributing to the glial scar, in mammals. Here we compare the cellular
      and molecular properties of ependymal zone cells and their environment across
      vertebrate classes. We point out communalities and differences between
      vertebrates capable of neuronal regeneration and those that are not. Comparisons
      like these may ultimately lead to the identification of factors that tip the
      balance for ependymal zone cells in mammals to produce appropriate neural cells
      for endogenous repair after spinal cord injury.

PMID- 29649498
TI  - The wakefulness promoting drug Modafinil causes adenosine receptor-mediated
      upregulation of receptor activator of nuclear factor kappaB ligand in
      osteoblasts: Negative impact of the drug on peak bone accrual in rats.
AB  - Modafinil is primarily prescribed for treatment of narcolepsy and other sleep
      associated disorders. However, its off-prescription use as a cognition enhancer
      increased considerably, specially among youths. Given its increasing use in young
      adults the effect of modafinil on peak bone accrual is an important issue but has
      never been investigated. Modafinil treatment to young male rats caused trabecular
      and cortical bone loss in tibia and femur, and reduction in biomechanical
      strength. Co-treatment of modafinil with alendronate (a drug that suppresses bone
      resorption) reversed the trabecular bone loss but failed to prevent cortical
      loss. Modafinil increased serum type 1 pro-collagen N-terminal protein (P1NP) and
      collagen type 1 cross-linked C-telopeptide (CTX-1) indicating a high turnover
      bone loss. The drug also increased receptor activator of nuclear factor kappaB
      ligand (RANKL) to osteoprotegerin (OPG) ratio in serum which likely resulted in
      increased osteoclast number per bone surface. Furthermore, conditioned medium
      from modafinil treated osteoblasts increased the expression of osteoclastogenic
      genes in bone marrow-derived macrophages and the effect was blocked by RANKL
      neutralizing antibody. In primary osteoblasts, modafinil stimulated cAMP
      production and using pharmacological approach, we showed that modafinil signalled
      via adenosine receptors (A2AR and A2BR) which resulted in increased RANKL
      expression. ZM-241,385 (an A2AR inhibitor) and MRS 1754 (an A2BR inhibitor)
      suppressed modafinil-induced upregulation of RANKL/OPG ratio in the calvarium of
      new born rat pups. Our data suggests that by activating osteoblast adenosine
      receptors modafinil increases the production of osteoclastogenic cytokine, RANKL
      that in turn results in high turnover bone loss in young rats.

PMID- 29649500
TI  - Cancer development and therapy resistance: spotlights on the dark side of the
      genome.
AB  - Cancer research has been focusing so far on genetic alterations in protein-coding
      genes. However, mounting evidence underlines the importance of epigenetic and
      post-transcriptional events in cancer progression and therapy resistance.
      Moreover, recent genome-wide studies show that disease-causing mutations and
      chromosome rearrangements often span areas of the genome that do not contain any
      known protein-coding gene. This finding is not surprising, considering that even
      though the vast majority of the human genome is transcribed, only a minor portion
      (accounting for less than 2%) encodes for proteins. Among the various classes of
      transcribed RNAs, long non-coding RNAs are attractive biomarkers and therapeutic
      targets due to their disease- and stage-restricted expression. In addition, by
      taking part in all the major epigenetic and post-transcriptional programs in the
      cell, long non-coding RNAs are emerging as key regulators of stress responses and
      therefore they are important non-genetic players in cancer development and
      progression. Here I discuss the role of lncRNAs in cancer and their promises and
      pitfalls as biomarkers and therapeutic targets.

PMID- 29649501
TI  - Exposure to endocrine disruptors 17alpha-ethinylestradiol and estradiol
      influences cytochrome P450 1A1-mediated genotoxicity of benzo[a]pyrene and
      expression of this enzyme in rats.
AB  - Endocrine disruptors (EDs) are compounds that interfere with the balance of the
      endocrine system by mimicking or antagonising the effects of endogenous hormones,
      by altering the synthesis and metabolism of natural hormones, or by modifying
      hormone receptor levels. The synthetic estrogen 17alpha-ethinylestradiol (EE2)
      and the environmental carcinogen benzo[a]pyrene (BaP) are exogenous EDs whereas
      the estrogenic hormone 17beta-estradiol is a natural endogenous ED. Although the
      biological effects of these individual EDs have partially been studied
      previously, their toxicity when acting in combination has not yet been
      investigated. Here we treated Wistar rats with BaP, EE2 and estradiol alone or in
      combination and studied the influence of EE2 and estradiol on: (i) the expression
      of cytochrome P450 (CYP) 1A1 and 1B1 in rat liver on the transcriptional and
      translational levels; (ii) the inducibility of these CYP enzymes by BaP in this
      rat organ; (iii) the formation of BaP-DNA adducts in rat liver in vivo; and (iv)
      the generation of BaP-induced DNA adducts after activation of BaP with hepatic
      microsomes of rats exposed to BaP, EE2 and estradiol and with recombinant rat
      CYP1A1 in vitro. BaP acted as a strong and moderate inducer of CYP1A1 and 1B1 in
      rat liver, respectively, whereas EE2 or estradiol alone had no effect on the
      expression of these enzymes. However, when EE2 was administered to rats together
      with BaP, it significantly decreased the potency of BaP to induce CYP1A1 and 1B1
      gene expression. For EE2, but not estradiol, this also correlated with a
      reduction of BaP-induced CYP1A1 enzyme activity in rat hepatic microsomes.
      Further, while EE2 and estradiol did not form covalent adducts with DNA, they
      affected BaP-derived DNA adduct formations in vivo and in vitro. The observed
      decrease in BaP-DNA adduct levels in rat liver in vivo resulted from the
      inhibition of CYP1A1-mediated BaP bioactivation by EE2 and estradiol. Our results
      indicate that BaP genotoxicity mediated through its activation by CYP1A1 in rats
      in vivo is modulated by estradiol and its synthetic derivative EE2.

PMID- 29649502
TI  - A behavioral mechanistic investigation of the role of 5-HT1A receptors in the
      mediation of rat maternal behavior.
AB  - Previous work suggests that 5-HT1A receptors play a special role in rodent
      maternal aggression, but not in other aspects of maternal care (e.g. pup
      retrieval and nest building). The present study re-assessed the basic effects of
      5-HT1A activation or blockade on various maternal responses in postpartum female
      rats. We also examined the possible behavioral mechanisms underlying the maternal
      effects of 5-HT1A. Sprague-Dawley mother rats were injected with a 5-HT1A agonist
      8-OH-DPAT (0.1, 0.5 or 1.0 mg/kg, sc), a 5-HT1A antagonist WAY-101405 (0.1, 0.5
      or 1.0 mg/kg, sc) or 0.9% saline solution on postpartum days 3, 5, and 7.
      Maternal behavior was tested 30 min before, 30 min, 120 min, and 240 min after
      the injection. Acute and repeated 8-OH-DPAT treatment significantly disrupted pup
      retrieval, pup licking, nursing, and nest building in a dose-dependent fashion,
      whereas WAY-101405 had no effect at the tested doses. The 5-HT1A receptor
      specificity of 8-OH-DPAT's action was confirmed as its maternal disruption effect
      was reversed by pretreatment of WAY-100635 (a highly selective 5-HT1A receptor
      antagonist). Subsequent pup preference test found that 8-OH-DPAT did not decrease
      the pup preference over a novel object, thus no inhibition on maternal motivation
      or maternal affect. The pup separation test and pup retrieval on an elevated plus
      maze test also failed to find any motivational and motor impairment effect with 8
      OH-DPAT. However, 8-OH-DPAT at the maternal disruptive dose did disrupt the
      prepulse inhibition (a measure of attentional function) of acoustic startle
      response and enhanced the basal startle response. These findings suggest that
      stimulation of 5-HT1A receptors by 8-OH-DPAT impairs maternal care by partially
      interfering with the attentional processing or basal anxiety. More work is needed
      to further delineate the psychological and neuronal mechanisms underlying the
      maternal disruptive effect of 5-HT1A receptor activation.

PMID- 29649503
TI  - Modulating fluid intelligence performance through combined cognitive training and
      brain stimulation.
AB  - It is debated whether cognitive training of specific executive functions leads to
      far transfer effects, such as improvements in fluid intelligence (Gf). Within
      this context, transcranial direct current stimulation and recently also novel
      protocols such as transcranial random noise and alternating current stimulation
      are being investigated with regards to their ability to enhance cognitive
      training outcomes. We compared the effects of four different transcranial
      electrical brain stimulation protocols in combination with nine daily
      computerized training sessions on Gf. 82 participants were randomly assigned to
      receive transcranial direct current stimulation (tDCS), random noise stimulation
      (tRNS), multifocal alternating current stimulation at 40 Hz (mftACS), or
      multifocal tDCS (mftDCS) in combination with an adaptive and synergistic
      executive function (EF) training, or to a no-contact control group. EF training
      consisted of gamified tasks drawing on isolated as well as integrated executive
      functions (working memory, inhibition, cognitive flexibility). Transfer was
      assessed with a combined measure of Gf including three established tests
      (Bochumer Matrizentest - BOMAT, Raven's Advanced Progressive Matrices - RAPM, and
      Sandia Matrices). We found significant improvements in Gf for the tDCS, mftDCS,
      and tRNS groups when compared with the no-contact group. In contrast, the mftACS
      group did not improve significantly and showed a similar pattern as the no
      contact group. Mediation analyses indicated that the improvement in Gf was
      mediated through game progression in the mftDCS and tRNS group. Electrical brain
      stimulation in combination with sustained EF training can lead to transfer
      effects in Gf, which are mediated by training progression.

PMID- 29649504
TI  - Tau pathology and neurochemical changes associated with memory dysfunction in an
      optimised murine model of global cerebral ischaemia - A potential model for
      vascular dementia?
AB  - Cerebral ischemia is known to be a major cause of death and the later development
      of Alzheimer's disease and vascular dementia. However, ischemia induced cellular
      damage that initiates these diseases remain poorly understood. This is primarily
      due to lack of clinically relevant models that are highly reproducible. Here, we
      have optimised a murine model of global cerebral ischaemia with multiple markers
      to determine brain pathology, neurochemistry and correlated memory deficits in
      these animals. Cerebral ischaemia in mice was induced by bilateral common carotid
      artery occlusion. Following reperfusion, the mice were either fixed with 4%
      paraformaldehyde or decapitated under anaesthesia. Brains were processed for
      Western blotting or immunohistochemistry for glial (GLT1) and vesicular (VGLUT1,
      VGLUT2) glutamate transporters and paired helical filament (PHF1) tau. The PHF1
      tau is the main component of neurofibrillary tangle, which is the pathological
      hallmark of Alzheimer's disease and vascular dementia. The novel object
      recognition behavioural assay was used to investigate the functional cognitive
      consequences in these mice. The results show consistent and selective neuronal
      and glial cell changes in the hippocampus and the cortex together with
      significant reductions in GLT1 (***P < 0.001), VGLUT1 (**P < 0.01) and VGLUT2
      (***P < 0.001) expressions in the hippocampus in occluded mice as compared to
      sham-operated animals. These changes are associated with increased PHF1 (***P <
      0.0001) protein and a significant impairment of performance (*p < 0.0006, N =
      6/group) in the novel object recognition test. This model represents a useful
      tool for investigating cellular, biochemical and molecular mechanisms of global
      cerebral ischaemia and may be an ideal preclinical model for vascular dementia.

PMID- 29649505
TI  - Do HEMA-free adhesive systems have better clinical performance than HEMA
      containing systems in noncarious cervical lesions? A systematic review and meta
      analysis.
AB  - OBJECTIVES: To determine through a systematic review whether HEMA-free adhesive
      systems have better clinical performance than HEMA-containing systems in
      noncarious cervical lesion (NCCL) restorations. SOURCES: We systematically
      searched PubMed, The Cochrane Library, Scopus, Web of Science, and Open Grey
      databases using MeSH terms, synonyms, and keywords, with no language or date
      restriction. The reference lists of included articles were manually searched.
      STUDY SELECTION: Randomized controlled clinical trials comparing the
      effectiveness of HEMA-free and HEMA-containing adhesive systems in NCCL
      restorations were included. The risk of bias in the included studies was assessed
      and classified through the Cochrane Collaboration's common scheme for bias.
      Quantitative data were subgrouped according to the main clinical parameters
      evaluated, and heterogeneity was tested using I2 index. DATA: A total of 2889
      potentially relevant studies were identified. After title and abstract
      examination, 51 studies remained. Finally, 22 studies were included in the
      systematic review, totaling to 997 participants. Thus, 13 studies were classified
      as "low" risk of bias and nine as "unclear". These 22 studies were also included
      in the meta-analysis, and no significant statistical difference was found between
      the clinical performances of HEMA-free and HEMA-containing adhesive systems for
      all parameters analyzed: retention risk difference (RD) 0.03 [-0.01, 0.07] (p =
      0.13); marginal discoloration RD 0.02 [-0.01, 0.04] (p = 0.19); marginal
      adaptation RD -0.01 [-0.04, 0.01] (p = 0.34); caries RD 0.00 [-0.01, 0.01] (p =
      0.92); or postoperative sensitivity RD -0.00 [-0.02, 0.01] (p = 0.72) and for
      overall effect RD 0.00 [-0.01, 0.01] (p = 0.65). CONCLUSIONS: HEMA-free and HEMA
      containing adhesive systems showed a similar clinical performance in NCCL
      restorations. CLINICAL SIGNIFICANCE: Only the presence of HEMA does not indicate
      better clinical performance of adhesive systems.

PMID- 29649506
TI  - Clinical performance of glass ionomer cement and composite resin in Class II
      restorations in primary teeth: A systematic review and meta-analysis.
AB  - OBJECTIVES: This study compared the clinical performance of glass ionomer cement
      (GIC) compared to composite resin (CR) in Class II restorations in primary teeth.
      DATA: Literature search according to PRISMA guidelines including randomized
      controlled trials comparing Class II restorations performed with GIC, compared to
      CR, in primary teeth. SOURCES: PubMeb, Scopus, Web of Science, VHL, Cochrane
      Library, Clinical Trials and OpenGrey, regardless of date or language. STUDY: Ten
      studies were included in qualitative synthesis, and 9 in the meta-analyses (MA).
      Six studies were classified as low risk of bias, and 4 as "unclear".
      Heterogeneity ranged from null to high (0% to 73%). GIC and CR presented similar
      failure patterns (risk difference -0.04 [-0.11, 0.03]; p = 0.25, I2 = 51%), and
      the exclusion of studies with follow-up period <24 months, or grouping according
      to the type of GIC (conventional or resin-modified), or according to the type of
      isolation (cotton roll or rubber dam), or according to the evaluation criteria
      applied did not affect the pattern of the results obtained. GIC exhibited
      significantly lower values of secondary carious lesions (SCL) than CR (SCL: risk
      difference 0.06 [0.02, 0.10], p = 0.008, I2 = 0%). The materials presented
      similar performance (p > 0.05) regarding the overall effect, as well as for
      marginal discoloration, marginal adaptation and anatomical form. The superiority
      of GIC was maintained when resin-modified GIC and rubber dam isolation were
      analyzed separately. CONCLUSIONS: GIC and CR presented similar clinical
      performance for all criteria analyzed, except for secondary carious lesions, in
      which GIC presented superior performance, especially for the resin-modified GIC
      and with rubber dam isolation.

PMID- 29649507
TI  - Effects of anthraquinones from Cassia occidentalis L. on ovalbumin-induced
      airways inflammation in a mouse model of allergic asthma.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Cassia occidentalis Linn. is a traditional
      ayruvedic edible shrub containing anthraquinones (AQs) as the principle active
      constituents. In folk medicine, it has a variety of uses including treatment of
      whooping cough ('pertussis') and inflammatory diseases. Despite these
      applications, limited data are available to validate the effects of C.
      occidentalis AQs on airways inflammation in asthma. AIM OF THE STUDY: To explore
      the anti-inflammatory potential of AQs extracted from C. occidentalis using an in
      vivo model of ovalbumin (OVA)-induced asthma. MATERIALS AND METHODS: Extraction
      and optimization of AQs from C. occidentalis was performed by mechanochemistry.
      Allergic asthma in BALB/c mice was sensitized and challenged by OVA, and the
      effects of AQs investigated in a mouse model. OVA-specific IgE concentrations in
      serum, and Th1/Th2 cytokine (IL-4, IL-5, IL-13 and IFN-gamma) concentrations,
      inflammatory cell counts and classification in bronchoalveolar lavage fluid
      (BALF) were determined. Histopathological evaluation of lung tissue was performed
      using hematoxylin and eosin (H&E), and periodic acid-schiff (PAS) staining.
      Th1/Th2 cytokine mRNA expression was analyzed using the 2-DeltaDeltaCt method.
      RESULTS: Treatment with AQs decreased inflammatory cell counts and production of
      Th2 cytokines (IL-4, IL-5 and IL-13) in BALF, and OVA-specific IgE in serum. In
      contrast,Th1 cytokine IFN-gamma production in BALF was promoted. AQs also
      decreased mRNA expression of Th1/Th2 cytokine in lung tissue. Histological
      studies demonstrated that AQs substantially inhibited OVA-induced cellular
      infiltration, mucus hypersecretion and goblet cell hyperplasia in the lung.
      CONCLUSIONS: These findings demonstrated the inhibitory effects of AQs, derived
      from C. occidentalis, on OVA-induced allergic asthma in mice. The results suggest
      a promising ethnopharmacological use for AQs in patients with asthma.

PMID- 29649508
TI  - Behavioral fever decreases metabolic response to lipopolysaccharide in yellow
      Cururu toads (Rhinella icterica).
AB  - Ectothermic vertebrates develop behavioral fever in response to bacterial
      products, with potential corresponding metabolic costs associated with immune
      stimulation. Although behavioral fever has been described in several taxa under
      laboratory conditions, some important questions regarding metabolic response to
      bacterial products at different temperatures and effectiveness of behavioral
      fever remain open. Many ectotherms, such as nocturnal anurans, may be active in
      the field at environmental conditions that restrict thermoregulation during the
      immune response. How does the metabolic response to bacterial products under
      ecologically relevant but unfavorable thermal field conditions compare to that
      measured in fever thermal preferendum? Additionally, are there differences in the
      partitioning of metabolic costs associated with immune stimulation and Arrhenius
      effect (biochemical reactions rate) at normal versus fever thermal preferendum?
      We compared the energy expenditure untreated and LPS-treated yellow Cururu toads
      (Rhinella icterica) at temperature corresponding to field activity during winter
      nights, and at normal and fever thermal preferendum. It was hypothesized that the
      metabolic response to LPS would be proportionally lower at higher body
      temperatures. To test these hypotheses, we measured temperature in the field
      during night using agar models, as well as normal and fever thermal preferendum
      of the toads within a thermal gradient. Subsequently, we measured the toad's
      metabolic rates at mean agar models temperature, as well as at normal and fever
      thermal preferendum. Lastly, we calculated the Metabolic response to LPS as the
      ratio between MRLPS/MRSaline in each of these mean temperatures. Our results show
      that metabolic rates do not increase in response to LPS at the agar models
      temperature typical of the winter nights under which theses toads maintain
      reproductive activity. Moreover, LPS treatment increased the metabolic costs
      relative to Arrhenius effects at normal thermal preferendum but not at fever
      thermal preferendum. In this way, metabolic response to LPS was comparative lower
      at fever than normal thermal preferendum in yellow Cururu toads.

PMID- 29649509
TI  - Cybersickness-related changes in brain hemodynamics: A pilot study comparing
      transcranial Doppler and near-infrared spectroscopy assessments during a virtual
      ride on a roller coaster.
AB  - Our aim was to assess cerebral blood flow changes during cybersickness.
      Transcranial Doppler (TCD) ultrasound and near infrared spectroscopy (NIRS) were
      used separately in two independent experiments. In both studies, a 15-min virtual
      roller coaster ride was used as a provocative visual stimulus. Subjective nausea
      ratings were obtained at 1 min intervals. The TCD study was performed in 14
      healthy subjects (8 males and 6 females); in this study we also measured heart
      rate and arterial pressure. In a separate study a 52-channel NIRS device (Hitachi
      ETG-4000) was used to monitor activated brain regions by measuring oxy-hemoglobin
      (HbO2) concentration in 9 healthy subjects (4 male, 5 females). The TCD study
      results showed a significant increase in systolic (+3.8 +/- 1.8 mm Hg) and
      diastolic (+6.7 +/- 1.3 mm Hg) pressure at the end of the virtual ride (maximum
      nausea) compared to baseline (no nausea). We also found that middle cerebral
      artery (MCA) and posterior cerebral artery (PCA) systolic flow velocity decreased
      significantly at the end of the ride when compared to baseline values. Likewise,
      the relative systolic and diastolic conductance in the MCA decreased
      significantly (-0.03 +/- 0.02 cm * s-1 * mm Hg-1, t, p = 0.0058 and -0.03 +/-
      0.01 cm * s-1 * mm Hg-1, p = 0.05, respectively) at maximum nausea when compared
      to no nausea. Additionally, there was a significant decrease (-0.02 +/- 0.01 cm *
      s-1 * mm Hg-1, p = 0.03) in the relative systolic conductance in the PCA at the
      end of the ride. Analysis of the NIRS results showed a significant increase in
      HbO2 concentration in 15/52 channels in parieto-temporal regions of both
      hemispheres in participants who experienced motion sickness symptoms during the
      experiment. This increase in HbO2 concentration correlated with increasing nausea
      and motion sickness symptoms. We conclude that cybersickness causes complex
      changes in cerebral blood flow, with an increase in perfusion in some cortical
      regions, but with a decrease of global cerebral perfusion.

PMID- 29649510
TI  - ILT4 functions as a potential checkpoint molecule for tumor immunotherapy.
AB  - Immune checkpoint blockade therapy targeting CTLA4 and PD-1/PD-L1 is a promising
      strategy in the treatment of different types of cancers. However, the clinical
      success rates of these therapies are still moderate and varied among cancer
      types. Therefore, identification of alternative and novel checkpoint molecules or
      interrupting tolerogenic pathways is urgently needed for successful tumor
      immunotherapy. Immunoglobulin-like transcript 4 (ILT4) is as an immunosuppressive
      molecule predominantly expressed in myeloid cells, including monocytes,
      macrophages, dendritic cells and granulocytes. Recent studies revealed that ILT4
      is also enriched in tumor cells and stroma cells in the tumor microenvironment of
      various malignancies, modulating the biological behaviors of tumor cells and
      promoting their immune escape. However, the underlying mechanisms responsible for
      ILT4-mediated tumor development and progression are still poorly understood. In
      this review, we explore the functional role of ILT4 as a novel checkpoint
      molecule in cancers. We specifically discuss the mechanisms mediated by ILT4 for
      controlling tumor malignant behaviors, impairing effector anti-tumor immune
      responses, and sustaining the tumor suppressive microenvironment. We also
      highlight the potential role of ILT4 as a novel immune checkpoint target for
      tumor immunotherapy. Improved understanding of these issues is critical for
      elucidation of the role of ILT4 in tumor pathogenesis and should open new avenues
      for cancer immunotherapy specifically targeting this novel and alternative
      checkpoint molecule.

PMID- 29649511
TI  - Interference of carbidopa and other catechols with reactions catalyzed by
      peroxidases.
AB  - BACKGROUND: A number of compounds, including ascorbic acid, catecholamines,
      flavonoids, p-diphenols and hydrazine derivatives have been reported to interfere
      with peroxidase-based medical diagnostic tests (Trinder reaction) but the
      mechanisms of these effects have not been fully elucidated. METHODS: Reactions of
      bovine myeloperoxidase with o-dianisidine, bovine lactoperoxidase with ABTS and
      horseradish peroxidase with 4-aminoantipyrine/phenol in the presence of
      carbidopa, an anti-Parkinsonian drug, and other catechols, including l-dopa, were
      monitored spectrophotometrically and by measuring hydrogen peroxide consumption.
      RESULTS: Chromophore formation in all three enzyme/substrate systems was blocked
      in the presence of carbidopa and other catechols. However, the rates of hydrogen
      peroxide consumption were not much affected. Irreversible enzyme inhibition was
      also insignificant. CONCLUSIONS: Tested compounds reduced the oxidation products
      or intermediates of model substrates thus preventing chromophore formation. This
      interference may affect interpretation of results of diagnostic tests in samples
      from patients with Parkinson's disease treated with carbidopa and l-dopa. GENERAL
      SIGNIFICANCE: This mechanism allows prediction of interference in peroxidase
      based diagnostic tests for other compounds, including drugs and natural products.

PMID- 29649513
TI  - Neurofeedback Control of the Human GABAergic System Using Non-invasive Brain
      Stimulation.
AB  - Neurofeedback has been a powerful method for self-regulating brain activities to
      elicit potential ability of human mind. GABA is a major inhibitory
      neurotransmitter in the central nervous system. Transcranial magnetic stimulation
      (TMS) is a tool that can evaluate the GABAergic system within the primary motor
      cortex (M1) using paired-pulse stimuli, short intracortical inhibition (SICI).
      Herein we investigated whether neurofeedback learning using SICI enabled us to
      control the GABAergic system within the M1 area. Forty-five healthy subjects were
      randomly divided into two groups: those receiving SICI neurofeedback learning or
      those receiving no neurofeedback (control) learning. During both learning
      periods, subjects made attempts to change the size of a circle, which was altered
      according to the degree of SICI in the SICI neurofeedback learning group, and
      which was altered independent of the degree of SICI in the control learning
      group. Results demonstrated that the SICI neurofeedback learning group showed a
      significant enhancement in SICI. Moreover, this group showed a significant
      reduction in choice reaction time compared to the control group. Our findings
      indicate that humans can intrinsically control the intracortical GABAergic system
      within M1 and can thus improve motor behaviors by SICI neurofeedback learning.
      SICI neurofeedback learning is a novel and promising approach to control our
      neural system and potentially represents a new therapy for patients with abnormal
      motor symptoms caused by CNS disorders.

PMID- 29649512
TI  - 14-3-3 protein directly interacts with the kinase domain of calcium/calmodulin
      dependent protein kinase kinase (CaMKK2).
AB  - BACKGROUND: Calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) is a
      member of the Ca2+/calmodulin-dependent kinase (CaMK) family involved in
      adiposity regulation, glucose homeostasis and cancer. This upstream activator of
      CaMKI, CaMKIV and AMP-activated protein kinase is inhibited by phosphorylation,
      which also triggers an association with the scaffolding protein 14-3-3. However,
      the role of 14-3-3 in the regulation of CaMKK2 remains unknown. METHODS: The
      interaction between phosphorylated CaMKK2 and the 14-3-3gamma protein, as well as
      the architecture of their complex, were studied using enzyme activity
      measurements, small-angle x-ray scattering (SAXS), time-resolved fluorescence
      spectroscopy and protein crystallography. RESULTS: Our data suggest that the 14-3
      3 protein binding does not inhibit the catalytic activity of phosphorylated
      CaMKK2 but rather slows down its dephosphorylation. Structural analysis indicated
      that the complex is flexible and that CaMKK2 is located outside the
      phosphopeptide-binding central channel of the 14-3-3gamma dimer. Furthermore, 14
      3-3gamma appears to interact with and affect the structure of several regions of
      CaMKK2 outside the 14-3-3 binding motifs. In addition, the structural basis of
      interactions between 14-3-3 and the 14-3-3 binding motifs of CaMKK2 were
      elucidated by determining the crystal structures of phosphopeptides containing
      these motifs bound to 14-3-3. CONCLUSIONS: 14-3-3gamma protein directly interacts
      with the kinase domain of CaMKK2 and the region containing the inhibitory
      phosphorylation site Thr145 within the N-terminal extension. GENERAL
      SIGNIFICANCE: Our results suggested that CaMKK isoforms differ in their 14-3-3
      mediated regulations and that the interaction between 14-3-3 protein and the N
      terminal 14-3-3-binding motif of CaMKK2 might be stabilized by small-molecule
      compounds.

PMID- 29649515
TI  - A biopsychosocial model of body image, disordered eating, and breastfeeding among
      postpartum women.
AB  - BACKGROUND: The aim of the current study was to test a biopsychosocial model of
      body image, eating, and feeding attitudes among postpartum women. Specifically,
      the model predicted that desired weight-loss, depressive symptoms, and body
      surveillance would predict body dissatisfaction and appearance-related barriers
      to breastfeeding, which in turn would predict maternal disordered eating and
      breastfeeding self-efficacy. METHODS: Data from 151 women, mean age = 32.77
      (4.47) years, who provided complete data in response to an online survey were
      analyzed. RESULTS: Path analysis revealed that after minor modifications, the
      biopsychosocial model was a good fit to the data. Desired weight-loss, depressive
      symptoms, and body surveillance were associated with higher levels of disordered
      eating and lower levels of breastfeeding self-efficacy directly, as well as
      indirectly through body dissatisfaction and appearance-related barriers to
      breastfeeding. CONCLUSION: Findings provide support for an integrated
      biopsychosocial model of body image concerns, and eating and feeding attitudes
      among postpartum women as well as highlighting the need for additional support
      around body image, eating, and breastfeeding following childbirth. Our study has
      clinical implications for healthcare providers working with new mothers and can
      be used to inform postpartum psychoeducation efforts addressing breastfeeding,
      weight loss expectations and body image concerns.

PMID- 29649514
TI  - Endogenous Neuronal Replacement in the Juvenile Brain Following Cerebral
      Ischemia.
AB  - Replacement of dead neurons following ischemia, either via enhanced endogenous
      neurogenesis or stem cell therapy, has long been sought. Unfortunately, while
      various therapies that enhance neurogenesis or stem cell therapies have proven
      beneficial in animal models, they have all uniformly failed to truly replace dead
      neurons in the ischemic core to facilitate long-term recovery. Remarkably, we
      observe robust repopulation of medium-spiny neurons within the ischemic core of
      juvenile mice following experimental stroke. Despite extensive neuronal cell
      death in the injured striatum of both juveniles and adults at acute time points
      after ischemia (24 h and 7 d), mature newborn neurons replaced lost striatal
      neurons at 30 d post-ischemia. This neuronal repopulation was found only in
      juveniles, not adults, and importantly, was accompanied by enhanced post-ischemic
      behavioral recovery at 30 d. Ablation of neurogenesis using irradiation prevented
      neuronal replacement and functional recovery in MCAo-injured juvenile mice. In
      contrast, findings in adults were consistent with previous reports, that newborn
      neurons failed to mature and died, offering little therapeutic potential. These
      data provide support for neuronal replacement and consequent functional recovery
      following ischemic stroke and new targets in the development of novel therapies
      to treat stroke.

PMID- 29649516
TI  - "Mom, quit fat talking-I'm trying to eat (mindfully) here!": Evaluating a
      sociocultural model of family fat talk, positive body image, and mindful eating
      in college women.
AB  - A growing evidence base confirms sociocultural theory's predictions regarding the
      influence of direct exposure to family factors (e.g., parental commentary) in
      promoting disordered eating behavior as mediated by negative body image.
      Nevertheless, this model has not been specifically applied to investigating
      indirect or vicarious exposure to family communications (e.g., negative body
      talk) in estimating mindful eating behavior via positive body image intervening
      variables. Therefore, to address this gap the present study provided a
      preliminary evaluation of the indirect effects of overhearing family fat talk
      through both body appreciation and functional body appreciation in predicting
      mindful eating among undergraduate females. Participants included 333 women
      attending a large southeastern public university who completed measures of
      mindful eating, family fat talk, body appreciation, and functional body
      appreciation via an online survey platform. Results indicated that family fat
      talk was inversely associated with mindful eating, body appreciation, and
      functional body appreciation. Whereas engaging in mindful eating positively
      corresponded with both positive body image indices. A regression model
      controlling for BMI also revealed that an orientation towards appreciating what
      the body can do (and not a general appreciation of the body) helped explain the
      inverse association between family fat talk and mindful eating. Our initial
      findings tentatively suggest that focusing on the self-objectifying and self
      denigrating body-related commentary of family members may disrupt attention to
      one's own appreciation of the (internal) workings of the body thereby undermining
      the mindful eating process. Implications for further expanding the translation of
      sociocultural theory in the context of positive body image and mindful eating are
      considered.

PMID- 29649517
TI  - Effect of nisin on microbiome-brain-gut axis neurochemicals by Escherichia coli
      induced diarrhea in mice.
AB  - The effects of nisin on the neurochemicals, Aquaporin-3 (AQP-3) and intestinal
      microorganisms in the brain-gut axis of mice were analyzed by using enzyme linked
      immune sorbent assay (ELISA) and high throughput sequencing in this
      investigation, to further revealed the relationship between intestinal flora
      abundance in mice and neurochemicals in the brain-gut axis. Using HE staining
      found damage of structure of small intestine villi in the model group
      (Escherichia coli O1, E. coli O1). Compared with normal control and ciprofloxacin
      groups, using ELISA showed that nisin increased the highest norepinephrine (NE)
      expression in the brain, expression of 5-hydroxytryptamine (5-HT) and dopamine
      (DA) in the duodenum, and increased the expression of AQP-3 in jejunum. Using
      high-throughput sequencing showed the highest diversity of cecal microflora in
      nisin group (ACE-index = 1417.25, Chao1-index = 1378.45), but the cecal
      microflora in the negative control group (ACE-index = 969.54, Chao1-index =
      340.29) exhibited the lowest species diversity. Our data indicated that nisin
      regulates neurochemicals, AQP-3 and cecal microflora imbalance in mice.

PMID- 29649518
TI  - Design and optimization of gastro-floating sustained-release tablet of
      pregabalin: In vitro and in vivo evaluation.
AB  - Pregabalin is a promising drug for the treatment of neuropathic pain, a chronic
      disease affecting a large population needing long-term treatment. However, due to
      its short half-life, the commercial tablet has to be administered 2-3 times per
      day, with inconvenience for patient and fluctuations of plasma concentration. In
      this study, a gastro-floating drug delivery system of pregabalin was developed to
      prolong the gastric retention of drugs absorbed or act in stomach or upper
      gastrointestinal tract. First of all, it was proved that the drug was mainly
      absorbed in stomach and upper gastrointestinal tract. The final formulation was
      optimized in consideration of buoyancy and drug release profile. The gastro
      floating tablet was prepared with hydroxypropyl methylcellulose (HPMC) as
      sustained-release matrix, lipophilic cetyl alcohol as floating-assistance agent
      and other excipients to achieve satisfying buoyancy and sustained release
      performance with mechanisms of diffusion and matrix erosion. Food exhibited
      significant effect on the pharmacokinetics of gastro-floating tablet and
      conventional capsule. Compared with conventional capsules, the relative
      bioavailability of gastro-floating tablet in fasted conditions or in fed
      conditions was only 62.47 +/- 10.80% and 100.98 +/- 17.25% respectively, even
      though the gastro-floating tablet obtained decreased Cmax and prolonged Tmax in
      fasted and fed conditions. Besides, good in vivo-in vitro correlation of the
      gastro-floating tablet was established. In summary, a gastro-floating tablet of
      pregabalin exhibiting desired buoyancy and release profiles was designed, and the
      tablet expressed significantly sustained-release behavior in fed conditions with
      good in vivo-in vitro correlation. The designed gastro-floating system is a
      promising choice for the patients to relieve neuropathic pain.

PMID- 29649519
TI  - Limitations of high dose carrier based formulations.
AB  - PURPOSE: This study was performed to investigate how increasing the active
      pharmaceutical ingredient (API) content within a formulation affects the
      dispersion of particles and the aerosol performance efficiency of a carrier based
      dry powder inhalable (DPI) formulation, using a custom dry powder inhaler (DPI)
      development rig. METHODS: Five formulations with varying concentrations of API
      beclomethasone dipropionate (BDP) between 1% and 30% (w/w) were formulated as a
      multi-component carrier system containing coarse lactose and fine lactose with
      magnesium stearate. The morphology of the formulation and each component were
      investigated using scanning electron micrographs while the particle size was
      measured by laser diffraction. The aerosol performance, in terms of aerodynamic
      diameter, was assessed using the British pharmacopeia Apparatus E cascade
      impactor (Next generation impactor). Chemical analysis of the API was observed by
      high performance liquid chromatography (HPLC). RESULTS: Increasing the
      concentration of BDP in the blend resulted in increasing numbers and size of
      individual agglomerates and densely packed BDP multi-layers on the surface of the
      lactose carrier. BDP present within the multi-layer did not disperse as
      individual primary particles but as dense agglomerates, which led to a decrease
      in aerosol performance and increased percentage of BDP deposition within the
      Apparatus E induction port and pre-separator. CONCLUSION: As the BDP
      concentration in the blends increases, aerosol performance of the formulation
      decreases, in an inversely proportional manner. Concurrently, the percentage of
      API deposition in the induction port and pre-separator could also be linked to
      the amount of micronized particles (BDP and Micronized composite carrier) present
      in the formulation. The effect of such dose increase on the behaviour of aerosol
      dispersion was investigated to gain greater insight in the development and
      optimisation of higher dosed carrier-based formulations.

PMID- 29649521
TI  - Modelling motor neuron disease in fruit flies: Lessons from spinal muscular
      atrophy.
AB  - Motor neuron disease (MND) is characterised by muscle weakness and paralysis
      downstream of motor neuron degeneration. Genetic factors play a major role in
      disease pathogenesis and progression. This is best underscored by spinal muscular
      atrophy (SMA), the most common MND affecting children. Although SMA is caused by
      homozygous mutations in the survival motor neuron 1 (SMN1) gene, partial
      compensation by the paralogous SMN2 gene and/or genetic modifiers influence age
      of onset and disease severity. SMA is also the first MND that is treatable thanks
      to the recent development of a molecular-based therapy. This key milestone was
      possible following an intense research campaign in which animal models had a
      starring role. In this review, we specifically focus on the fruit fly Drosophila
      melanogaster and highlight its sterling contributions aimed at furthering our
      understanding of SMA pathogenesis. Methods of gene disruption utilised to
      generate SMA fly models are discussed and ways through which neuromuscular
      defects have been characterised are elaborated on. A phenotypic overlap with
      patients and mammalian models, allowed the use of SMA fly models to identify
      genetic modifiers, hence spurring investigators to discover pathways that are
      perturbed in disease. Targeting these can potentially lead to complimentary
      therapies for SMA. The same output is expected from the use of SMA fly models to
      identify therapeutic compounds that have an ameliorative effect. We believe that
      lessons gained from SMA will allow researchers to eagerly exploit Drosophila to
      confirm novel genes linked to MND, reveal disease mechanisms and ultimately
      identify therapeutics.

PMID- 29649520
TI  - Development and validation of a prognostic score to predict tuberculosis
      mortality.
AB  - OBJECTIVE: To develop and validate a simple prognostic scoring system to predict
      the mortality risk during treatment in tuberculosis patients. METHODS: Using data
      from the CDC's Tuberculosis Genotyping Information Management System of TB
      patients in Texas reported from 01/2010 to 12/2016, age >= 15 years and having an
      outcome as "completed" or "died", we developed and validated a prognostic
      mortality scoring system-based logistic regression beta-coefficients. RESULTS:
      The developmental and validation cohorts consisted of 3378 and 3377 patients,
      respectively. The score used 9 demographic and clinical characteristics, which
      are usually available at the patient's initial visits to a healthcare facility.
      Prognostic scores were categorized into three groups that predicted mortality:
      low-risk (<15 points), medium-risk (15-18 points), and high-risk (>18 points).
      The model had excellent discrimination and calibration with an area under the
      receiver operating characteristic curve of 0.82 and 0.80, and a non-significant
      Hosmer-Lemeshow test P = 0.514 and P = 0.613 in the developmental and validation
      cohorts, respectively. CONCLUSION: Our validated TB prognostic scoring system,
      which used demographic and clinical characteristics available at the patient's
      initial visits, can be a practical tool for health care providers to identify TB
      patients with high mortality risk so that appropriate treatment, medical supports
      and follow-up resources could be appropriately allocated.

PMID- 29649522
TI  - Triptolide up-regulates metabotropic glutamate receptor 5 to inhibit microglia
      activation in the lipopolysaccharide-induced model of Parkinson's disease.
AB  - Metabotropic glutamate receptor (mGlu)5 regulates microglia activation, which
      contributes to inflammation. However, the role of mGlu5 in neuroinflammation
      associated with Parkinson's disease (PD) remains unclear. Triptolide (T10) exerts
      potent immunosuppressive and anti-inflammatory effects and protects neurons by
      inhibiting microglia activation. In this study, we investigated the role of mGlu5
      in the anti-inflammatory effect of T10 in a lipopolysaccharide (LPS)-induced PD
      model. In cultured BV2 cells and primary microglia, blocking mGlu5 activity or
      knocking down its expression abolished T10-inhibited release of proinflammatory
      cytokines induced by LPS. Moreover, T10 up-regulated mGlu5 expression decreased
      by LPS through enhancing mRNA expression and protein stability. T10 also reversed
      the reduction in mGlu5 membrane localization and modulated receptor-mediated
      mitogen-activated protein kinase activity induced by LPS. Pharmacological
      inhibition of signaling molecules increased nitric oxide level and inducible
      nitric oxide synthase (iNOS), tumor necrosis factor-alpha, and interleukin (IL)
      1beta and -6 transcript levels that were downregulated by treatment with T10.
      Consistent with these in vitro findings, blocking mGlu5 attenuated the anti
      inflammatory effects of T10 in an LPS-induced PD model and blocked the decreases
      in the number and morphology of ionized calcium binding adaptor molecule 1
      positive microglia and LPS-induced iNOS protein expression caused by T10
      treatment. Besides, mGlu5 mediated the effect of T10 on microglia-induced
      astrocyte activation in vitro and in vivo. The findings provide evidence for a
      novel mechanism by which mGlu5 regulates T10-inhibited microglia activation via
      modulating protein expression of the receptor and its intracellular signaling.
      The study might contribute to the biological effects of Chinese herbs as an
      approach for protecting against neurotoxicity in PD.

PMID- 29649523
TI  - Prediction of the antimicrobial activity of walnut (Juglans regia L.) kernel
      aqueous extracts using artificial neural network and multiple linear regression.
AB  - The mathematical model was established to determine the diameter of inhibition
      zone of the walnut extract on the twelve bacterial species. Type of extraction,
      concentration, and pathogens were taken as input variables. Two models were used
      with the aim of designing this system. One of them was developed with artificial
      neural networks (ANN), and the other was formed with multiple linear regression
      (MLR). Four common training algorithms were used. Levenberg-Marquardt (LM),
      Bayesian regulation (BR), scaled conjugate gradient (SCG) and resilient back
      propagation (RP) were investigated, and the algorithms were compared. Root mean
      squared error and correlation coefficient were evaluated as performance criteria.
      When these criteria were analyzed, ANN showed high prediction performance, while
      MLR showed low prediction performance. As a result, it is seen that when the
      different input values are provided to the system developed with ANN, the most
      accurate inhibition zone (IZ) estimates were obtained. The results of this study
      could offer new perspectives, particularly in the field of microbiology, because
      these could be applied to other type of extraction, concentrations, and
      pathogens, without resorting to experiments.

PMID- 29649524
TI  - Hantavirus - Lectures in geography.

PMID- 29649525
TI  - Complex analyses on clinical information systems using restricted natural
      language querying to resolve time-event dependencies.
AB  - PURPOSE: This paper reports on a generic framework to provide clinicians with the
      ability to conduct complex analyses on elaborate research topics using cascaded
      queries to resolve internal time-event dependencies in the research questions, as
      an extension to the proposed Clinical Data Analytics Language (CliniDAL).
      METHODS: A cascaded query model is proposed to resolve internal time-event
      dependencies in the queries which can have up to five levels of criteria starting
      with a query to define subjects to be admitted into a study, followed by a query
      to define the time span of the experiment. Three more cascaded queries can be
      required to define control groups, control variables and output variables which
      all together simulate a real scientific experiment. According to the complexity
      of the research questions, the cascaded query model has the flexibility of
      merging some lower level queries for simple research questions or adding a nested
      query to each level to compose more complex queries. Three different scenarios
      (one of them contains two studies) are described and used for evaluation of the
      proposed solution. RESULTS: CliniDAL's complex analyses solution enables
      answering complex queries with time-event dependencies at most in a few hours
      which manually would take many days. CONCLUSION: An evaluation of results of the
      research studies based on the comparison between CliniDAL and SQL solutions
      reveals high usability and efficiency of CliniDAL's solution.

PMID- 29649526
TI  - Research Electronic Data Capture (REDCap(r)) used as an audit tool with a built
      in database.
AB  - The aim of this study was to develop an audit tool with a built-in database using
      Research Electronic Data Capture (REDCap(r)) as part of an antimicrobial
      stewardship program at a regional hospital in the Central Denmark Region, and to
      analyse the need, if any, to involve more than one expert in the evaluation of
      cases of antimicrobial treatment, and the level of agreement among the experts.
      Patients treated with systemic antimicrobials in the period from 1 September 2015
      to 31 August 2016 were included, in total 722 cases. Data were collected
      retrospectively and entered manually. The audit was based on seven flow charts
      regarding: (1) initiation of antimicrobial treatment (2) infection (3)
      prescription and administration of antimicrobials (4) discontinuation of
      antimicrobials (5) reassessment within 48 h after the first prescription of
      antimicrobials (6) microbiological sampling in the period between suspicion of
      infection and the first administration of antimicrobials (7) microbiological
      results. The audit was based on automatic calculations drawing on the entered
      data and on expert assessments. Initially, two experts completed the audit, and
      in the cases in which they disagreed, a third expert was consulted. In 31.9% of
      the cases, the two experts agreed on all elements of the audit. In 66.2%, the two
      experts reached agreement by discussing the cases. Finally, 1.9% of the cases
      were completed in cooperation with a third expert. The experts assessed 3406 flow
      charts of which they agreed on 75.8%. We succeeded in creating an audit tool with
      a built-in database that facilitates independent expert evaluation using REDCap.
      We found a large inter-observer difference that needs to be considered when
      constructing a project based on expert judgements. Our two experts agreed on most
      of the flow charts after discussion, whereas the third expert's intervention did
      not have any influence on the overall assessment.

PMID- 29649527
TI  - Recommendations for Evaluation and Management of Pain in Patients With
      Mucopolysaccharidosis in Latin America.
AB  - The mucopolysaccharidosis (MPS) constitutes a heterogeneous group of rare genetic
      disorders caused by enzymatic deficiencies that lead to the accumulation of
      glycosaminoglycans. Several types of MPS are described, historically numbered
      from I to IX. Clinical observations strongly suggest the presence of chronic pain
      in patients with all types of MPS. There are few data in the literature on the
      evaluation and management of pain in these patients, a fact that can compromise
      the quality of life even more. Professionals with extensive experience in the
      care for patients with MPS held a meeting in April 2017 to discuss and propose
      recommendations for the evaluation and management of pain in patients with MPS in
      Latin America. This article summarizes the content of the discussions and
      presents the recommendations produced at the meeting. Patients with MPS present
      joint, bone, and muscle pain, as well as entrapment syndromes (spinal, optic
      nerve, carpal tunnel). The panel suggests the use of the following instruments
      for pain assessment: Face, Legs, Activity, Cry and Consolability Scale for
      children of up to four years of age and patients unable to communicate their
      pain; Child Health Assessment Questionnaire Scale; Facial Pain Scale and
      Numerical Pain Scale for patients of five to <18 years of age; Brief Pain
      Inventory and Short Form Health Survey 36 scales for patients aged 18 years or
      older. Based on the scores verified in these scales, the panel proposes
      pharmacological interventions for pain relief in this population of patients.

PMID- 29649528
TI  - Hyaluronic acid-based biopharmaceutical delivery and tumor-targeted drug delivery
      system.
AB  - Hyaluronic acid (HA) is a natural polysaccharide with good biocompatibility and
      degradability. HA and its derivatives can be used as sustained-release carriers
      for drugs, which can delay the release of drugs and have a long-acting effect.
      They can be used for the delivery of various drugs such as proteins, nucleic
      acids and anti-tumor drugs. HA and its derivatives can specifically bind to
      multiple receptors on the cell surface and can be used for targeted drug
      delivery, especially for the delivery of anti-tumor drugs. Thus, there are
      different forms of tumor-targeted drug delivery systems based on HA.

PMID- 29649529
TI  - Mesoporous silicate nanoparticles/3D nanofibrous scaffold-mediated dual-drug
      delivery for bone tissue engineering.
AB  - Controlled delivery systems play a critical role in the success of bone
      morphogenetic proteins (i.e., BMP2 and BMP7) for challenged bone repair. Instead
      of single-drug release that is currently and commonly prevalent, dual-drug
      delivery strategies are highly desired to achieve effective bone regeneration
      because natural bone repair process is driven by multiple factors. Particularly,
      angiogenesis is essential for osteogenesis and requires more than just one factor
      (e.g., Vascular Endothelial Growth Factor, VEGF). Therefore, we developed a novel
      mesoporous silicate nanoparticles (MSNs) incorporated-3D nanofibrous gelatin (GF)
      scaffold for dual-delivery of BMP2 and deferoxamine (DFO). DFO is a hypoxia
      mimetic drug that can activate hypoxia-inducible factor-1 alpha (HIF-1alpha), and
      trigger subsequent angiogenesis. Sustained BMP2 release system was achieved
      through encapsulation into large-pored MSNs, while the relative short-term
      release of DFO was engineered through covalent conjugation with chitosan to
      reduce its cytotoxicity and elongate its half-life. Both MSNs and DFO were
      incorporated onto a porous 3D GF scaffold to serve as a biomimetic osteogenic
      microenvironment. Our data indicated that DFO and BMP2 were released from a
      scaffold at different release rates (10 vs 28 days) yet maintained their
      angiogenic and osteogenic ability, respectively. Importantly, our data indicated
      that the released DFO significantly improved BMP2-induced osteogenic
      differentiation where the dose/duration was important for its effects in both
      mouse and human stem cell models. Thus, we developed a novel and tunable MSNs/GF
      3D scaffold-mediated dual-drug delivery system and studied the potential
      application of the both FDA-approved DFO and BMP2 for bone tissue engineering.

PMID- 29649530
TI  - Self-assembled hyaluronic acid nanoparticles: Implications as a nanomedicine for
      treatment of type 2 diabetes.
AB  - Self-assembled hyaluronic acid nanoparticles (HA-NPs) have been extensively
      investigated for biomedical and pharmaceutical applications owing to their
      biocompatibility and receptor-binding properties. Here, we report that an empty
      HA-NP itself not bearing any drug has therapeutic effects on adipose tissue
      inflammation and insulin resistance. HA-NPs inhibited not only the receptor
      mediated internalization of low-molecular-weight (LMW) free HA but also LMW free
      HA-induced pro-inflammatory gene expression in mouse primary bone marrow-derived
      macrophages (BMDMs) isolated from wild-type mice, but not in CD44-null (CD44-/-)
      BMDMs. An in vivo biodistribution study showed the distribution of HA-NPs and
      their co-localization with CD44 in adipose tissues including epididymal white
      adipose tissues (eWATs), but these were rarely observed in the eWATs of CD44-/-
      mice. In addition, CD44 expression and HA-NP accumulation in the eWATs were
      increased in mice with diet-induced obesity (DIO) compared to lean mice.
      Interestingly, treatment with HA-NPs in DIO mice suppressed adipose tissue
      inflammation as indicated by reduced macrophage content, the production of
      proinflammatory cytokines and NLRP3 inflammasome activity in eWATs, leading to
      improved insulin sensitivity and normalized blood glucose levels. Collectively,
      these results suggest that an empty HA-NP itself can be a therapeutic agent for
      the treatment of type 2 diabetes.

PMID- 29649531
TI  - Preparation, characterization and in vitro release of beta-galactosidase loaded
      polyelectrolyte nanoparticles.
AB  - Improving encapsulation efficacy (EE) and bioavailability of beta-galactosidase
      (beta-gal) is always a challenge due to its fragility. In this work, beta-gal
      loaded beta-chitosan (CS) nanoparticles (NPs) were successfully prepared based on
      ionic gelation technique and electrostatic attraction for improving its EE and in
      vitro releasing capacity. The particle size of beta-gal loaded low and high
      molecular weight (LMW and HMW) beta-CS NPs reached 584.37 and 652.46nm, with Zeta
      potential (ZP) of 26.37 and 16.46mV under the optimal conditions, respectively.
      In vitro release study conducted at pH4.5 and 7.4 showed that beta-gal loaded LMW
      and HMW beta-CS NPs with EE of 68.32 and 58.64% sustained the release of the beta
      gal over 12h. The beta-gal incorporated into beta-CS NPs was confirmed with the
      results of physicochemical and structural properties of beta-gal loaded beta-CS
      NPs, and prepared NPs had hardly any cytotoxicity in the range of 0.1-1.0mg/mL.
      The results indicated that beta-gal loaded beta-CS NPs could serve as non-toxic
      delivery carriers for the treatment of lactose intolerance.

PMID- 29649532
TI  - The retrogradation kinetics of starches of different botanical origin in the
      presence of glucose syrup.
AB  - The influence of glucose syrup on the retrogradation of cereal starches was
      investigated. Laboratory isolated starches from wheat (WS) and oats (OS - oat
      starch and ROS - residual oat starch) were used in this research. ROS was
      isolated from the flour left after the industrial separation of beta-glucans.
      Gelatinization temperature of oat starches (63.82 degrees C and 64.01 degrees C
      for OS and ROS, respectively) was higher than for WS (62.26 degrees C), whereas
      gelatinization enthalpy for oat starches (8.87J/g and 9.09J/g for OS and ROS,
      respectively) was lower than for WS (9.99J/g). Moreover, retrogradation
      percentage (%R) was similar for both oat starches (29.76% and 27.72% for OS and
      ROS, respectively), and was substantially lower than for WS (42.04%). The
      introduction of glucose syrup into system reduced the extent of the
      retrogradation. Rate of the process was suppressed for WS and ROS, whereas for OS
      it was increased. beta-Glucan production process had no significant effect on the
      gelatinization and retrogradation of oat starch.

PMID- 29649533
TI  - Chitosan nanoparticles as a biocompatible and efficient nanowagon for benzyl
      isothiocyanate.
AB  - A plethora of evidences support the health benefits of a sulfur containing
      compound called Benzyl Isothiocyanate. However, its therapeutic application is
      limited due to its low solubility, poor stability and inadequate bioavailability.
      The problem has been worked upon and resolved by the synthesis of biodegradable
      nanoparticles using chitosan as the controlled delivery nanowagon. The prepared
      nanoparticles have been characterized using UV-visible absorption spectroscopy,
      IR spectroscopy, XRD, TGA, TEM and FE-SEM. Results reveal that loading of benzyl
      isothiocyanate into chitosan nanoparticles increases its solubility and
      stability. The maximum encapsulation efficiency was obtained to be 64.68+/-4.7%
      with slow and sustained release of 77.78% in 144h at pH5.5. Clear enhancement in
      the stability of benzyl isothiocyanate that is sensitive to ultraviolet light has
      been showcased after its encompassment in the cationic polymer. Further the
      biosafety of the fabricated system has been demonstrated by haemolysis and its
      interaction with biomolecules. The antimicrobial activity connotes that the
      prepared nanoparticles can act as a useful and safe carrier for the loading of
      benzyl isothiocyanate making it a promising formulation for biological
      applications in future.

PMID- 29649534
TI  - A modified microemulsion method for fabrication of hydrogel Tragacanth
      nanofibers.
AB  - Tragacanth is a nontoxic, biodegradable and biocompatible polymer applied as a
      nanostructure form in various fields such as biomedicine and food industry. Here,
      hydrogel Tragacanth nanofibers were fabricated using a modified microemulsion
      method. The effective parameters on the fabrication of nanofibers such as
      emulsifier type, stirrer type, processing time and concentrations of emulsifier,
      Tragacanth and aluminum chloride were studied and the conditions were optimized
      for high quality nanofibers. SEM images indicated Tragacanth nanofiberswere
      successfully synthesized with average diameter of 50 nm and uniformdistribution.
      Appear a peak at 1110 cm-1 related to Al-C bonds and reduce intensity ofthe peaks
      at 1742 and 1629 cm-1 and in FT-IR spectrum of nanofibersprove the successfully
      synthesis. Further, the hydrogel properties of the synthesized nanofibers can be
      proved by the swelling of 142% and drying time of 3 h.

PMID- 29649535
TI  - Rhizoctonia solani fucomannogalactan: Chemical characterization and
      antiproliferative activity.
AB  - A fucomannogalactan from Rhizoctonia solani biomass was obtained after hot
      aqueous extraction and purified by freeze-thaw cycles and gel filtration
      chromatography on Sepharose CL-6B. The polysaccharide was homogeneous after
      HPSEC/RID analysis (Mw/Mn~1.1), displaying an average molecular weight of
      15.4*103Da. Its chemical structure was determined by methylation analysis (GC/MS)
      and spectroscopy (FTIR, 1D and 2D NMR). The polysaccharide had a branched alpha
      1,6-linked Galp backbone with 66% linear residues, a number of which were at O-3
      methylated. Side chains (34%) were always linked at O-2 positions of the main
      chain and consisted of single, non-reducing ends of alpha-d-Manp (6%) and alpha-l
      Fucp (28%). Analysis of its biological activity showed that the highly purified
      fucomannogalactan from R. solani inhibited the proliferation of colon cancer
      cells in vitro, but that it did not have the same activity against lung cancer
      cells.

PMID- 29649536
TI  - Characterization of Momordica charantia L. polysaccharide and its protective
      effect on pancreatic cells injury in STZ-induced diabetic mice.
AB  - A polysaccharide with a molecular weight of 13,029Da was isolated from Momordica
      charantia (MCP) fruit and purified by ion-exchange and size-exclusion
      chromatography. The isolated polysaccharide MCPIIa contained L-Rha, D-GalA, D
      Gal, D-Xyl, L-Ara in a molar ratio of 12:3.05:19.89:5.95:56. IR spectrum and NMR
      studies indicated that the MCPIIa sugar units were linked, via beta-glycosidic
      bonds, to a large number of arabinofuranose, glucuronic acid, and xylopyranosyl
      residues. In addition, the hypoglycemic effect of MCPIIa was investigated in
      streptozotocin (STZ)-induced diabetic mice. After STZ-induction, MCPIIa (100,
      200, or 300mg/kg body weight) was administered orally, once daily, for 28days.
      Glycemia in STZ-diabetogenic mice was significantly reduced, and compared with
      diabetes mellitus (DM) mice, serum insulin concentration increased significantly,
      following MCPIIa administration. Transmission electron microscopy showed an
      alleviation of STZ-lesions in pancreatic tissue from mice treated with MCPIIa.
      These results indicate that MCPIIa may be useful as an anti-diabetic agent.

PMID- 29649537
TI  - Transcriptome analysis revealed anti-obesity effects of the Sodium Alginate in
      high-fat diet -induced obese mice.
AB  - Human obesity and overweight, caused by accumulated of fat, is the most commonly
      phenomenon from all over the world, especially in Western countries and Chinese
      mainland during the past three decades. Sodium Alginate, a polysaccharide
      extracted from brown seaweeds, has been proved its strong ability on body weight
      loss and anti-inflammatory response. However, no studies have been explored the
      effects of Sodium Alginate on colonic transcriptome, especially in obese
      individuals. Therefore, the current study was designed to detect whether Sodium
      Alginate could remit obesity and ease chronic metabolism disease through
      strengthening the bio-functionality of the lower intestine, particularly in
      colon. The data showed after Sodium Alginate gavaged for four weeks, the body
      weight, fat accumulation, triglyceride and total cholesterol were ameliorated in
      high fat diet induced obese mice. Sodium Alginate also improved the blood glucose
      level and lipopolysaccharides in serum. Furthermore, data from RNA sequence
      indicated that there were significantly changes in several genes, which involved
      in lipid metabolism and carbohydrate metabolism. In conclusion, these results
      suggested that Sodium Alginate could effectively suppress obesity and obesity
      related metabolic syndromes, due to the colonic transcriptome changes.

PMID- 29649538
TI  - Identification of factors to increase efficacy of telemedicine screening for
      diabetic retinopathy in endocrinology practices using the Intelligent Retinal
      Imaging System (IRIS) platform.
AB  - AIMS: Diabetic retinopathy (DR) and diabetic macular edema (DME) can be evaluated
      using telemedicine systems, such as the Intelligent Retinal Imaging Systems
      (IRIS), in patients with Diabetes Mellitus (DM). In an endocrinology-based
      population utilizing IRIS we determine prevalence rates of DR and DME, and
      identify associated epidemiologic correlations. METHODS: This is a multicenter,
      retrospective chart review using screening data from IRIS. Centers for Disease
      Control and Prevention (CDC) data on epidemiologic variables (by county) namely,
      prevalence of DM, incidence of DM, obesity, and time of physical inactivity, were
      compared against prevalence rates of DR found at screening. RESULTS: A total of
      10,223 eyes of 5,242 patients with DM were imaged. DR and DME were noted in 1781
      (33.98%) and 226 imaging studies (4.31%) respectively. The coefficient of
      determination was greatest for incidence of DM (R2 = 0.92), followed by DM
      prevalence (R2 = 0.79), obesity, (R2 = 0.67), and physical inactivity (R2 =
      0.34). The presence of DR during screening varied significantly by county (p <
      0.001). CONCLUSIONS: Screening in counties with a higher incidence of DM led to a
      higher prevalence of identified DR at time of screening. The current work
      suggests that telemedicine screening in areas known to have a higher incidence of
      DM may be worthwhile.

PMID- 29649539
TI  - Switching to insulin glargine 300 U/mL: Is duration of prior basal insulin
      therapy important?
AB  - AIMS: To assess the impact of duration of prior basal insulin therapy on study
      outcomes in people with type 2 diabetes mellitus receiving insulin glargine 300
      U/mL (Gla-300) or insulin glargine 100 U/mL (Gla-100) for 6 months. METHODS: A
      post hoc patient-level meta-analysis of data from the EDITION 1 and 2 studies.
      Outcomes included: HbA1c, percentage of participants with >=1 confirmed or severe
      hypoglycaemic event at night (00:00-05:59 h) or any time (24 h), and body weight
      change. Data were analysed according to duration of prior basal insulin use: >0
      <=2 years, >2-<=5 years, >5 years. RESULTS: This meta-analysis included 1618
      participants. HbA1c change from baseline to month 6 was comparable between Gla
      300 and Gla-100 groups, regardless of duration of prior basal insulin therapy.
      The lower risk with Gla-300 versus Gla-100 of >=1 confirmed (<=3.9 mmol/L [<=70
      mg/dL]) or severe hypoglycaemic event, at night or any time (24 h), was
      unaffected by duration of prior basal insulin therapy. Similarly, weight change
      was unaffected by duration of prior basal insulin therapy. CONCLUSIONS: Switching
      to Gla-300 from other basal insulin therapies provided comparable glycaemic
      control with lower risk of hypoglycaemia versus Gla-100, regardless of duration
      of prior basal insulin therapy. CLINICAL TRIAL REGISTRATION: NCT01499082,
      NCT01499095 (ClinicalTrials.gov).

PMID- 29649540
TI  - Incidence, risk factors, and pregnancy outcomes of gestational diabetes mellitus
      using one-step versus two-step diagnostic approaches: A population-based cohort
      study in Isfahan, Iran.
AB  - AIMS: To study the incidence, risk factors, and pregnancy outcomes associated
      with gestational diabetes mellitus (GDM) diagnosed with one-step and two-step
      screening approaches. METHODS: 1000 pregnant women who were eligible and
      consented to participate underwent fasting plasma glucose testing at the first
      prenatal visit (6-14 weeks). The women free from GDM or overt diabetes were
      screened at 24-28 weeks using the 50-g glucose challenge test (GCT) followed by
      100-g, 3-h oral glucose tolerance test (OGTT) (two-step method). Regardless of
      the GCT result, all women underwent a 75-g, 2-h OGTT within one-week interval
      (one-step method). RESULTS: GDM incidence using the one-step and two-step methods
      was 9.3% (95% CI: 7.4-11.2) and 4.2% (95% CI: 2.9-5.5). GDM significantly
      increased the risk of macrosomia, gestational hypertension, preeclampsia, and
      cesarean section and older age and family history of diabetes significantly
      increased the risk of developing GDM in both approaches. In two-step method,
      higher pre-pregnancy body mass index and lower physical activity during pregnancy
      along with higher earlier cesarean section also increased significantly the risk
      of developing GDM. CONCLUSIONS: Despite a higher incidence of GDM using the one
      step approach, more risk factors for and a stronger effect of GDM on adverse
      pregnancy outcomes were found when using the two-step approach. Longer follow-up
      of women with and without GDM may change the results using both approaches.

PMID- 29649541
TI  - Efficacy and safety of sodium-glucose cotransporter 2 inhibitors in patients with
      type 2 diabetes and moderate renal function impairment: A systematic review and
      meta-analysis.
AB  - AIMS: A systematic review and meta-analysis was conducted to evaluate the
      clinical efficacy and safety of sodium-glucose cotransporter 2 (SGLT2) inhibitors
      in patients with type 2 diabetes (T2D) and moderate renal function impairment.
      METHODS: Embase, Medline, and Cochrane Central were searched, and randomized
      controlled trials comparing SGLT2 inhibitors to placebos and other drugs for T2D
      were collected. RESULTS: Seven RCTs with a total of 3307 participants were
      included, and the overall bias was low. In the patients with T2D and moderate
      renal function impairment (30 ml/min/1.73 m2 <= estimated glomerular filtration
      rate (eGFR) <60 ml/min/1.73 m2) compared with the placebo, SGLT2 inhibitors
      improved HbA1c significantly (WMD, -0.23%; 95% CI: -0.38 to -0.08), presented a
      lower incidence of hypoglycemia (30.1% vs. 34.6%; RR, 0.85; 95% CI: 0.76 to
      0.96), led to the reduction of eGFR (WMD, -1.74 ml/min/1.73 m2; 95% CI: -3.45 to 
      0.03), resulted in an obvious reduction in body weight (WMD, -1.45 kg; 95% CI: 
      2.01 to -0.89), and presented a similar risk of urinary tract infection and
      genital infection. CONCLUSIONS: SGLT2 inhibitors are safe, but mildly reduce the
      HbA1c level. The clinical significance of SGLT2 inhibitors in the target
      population was limited.

PMID- 29649543
TI  - Fate of Recurrent or Persistent Varicocele in the Era of Assisted Reproduction
      Technology: Microsurgical Subinguinal Redo Varicocelectomy Versus Observation.
AB  - OBJECTIVE: To compare sperm parameters, serum hormone levels, and pregnancy and
      miscarriage rates between the infertile men with recurrent or persistent
      varicocele who underwent microsurgical subinguinal redo varicocelectomy or had
      observation only. MATERIALS AND METHODS: The study included 217 primary infertile
      men with recurrent or persistent varicocele. The patients were divided into 2
      groups: 120 men underwent microsurgical subinguinal redo varicocelectomy, and 97
      had observation only. Differences in total motile sperm count and serum hormone
      levels, and pregnancy and miscarriage rates were compared between the 2 groups.
      RESULTS: The mean total motile sperm count increased from 20.93 +/- 2.87 to 45.54
      +/- 6.28 million in the microsurgical redo varicocelectomy group, and decreased
      from 16.62 +/- 2.75 to 15.6 +/- 2.81 million in the control group, revealing
      significant difference between the 2 groups (P = .000). Increase in total
      testosterone level was significantly higher in the microsurgical redo
      varicocelectomy group (+1.36 +/- 0.32 ng/mL) than in the control group (-0.23 +/-
      0.1 ng/mL) (P = .000). Of the couples, 63 achieved pregnancy in the microsurgical
      redo varicocelectomy group (52.5%), and 38 had pregnancy in the control group
      (39.2%) (P <.05). Spontaneous pregnancy rate was significantly higher in the
      microsurgical redo varicocelectomy group (39.7%) than in the control group
      (15.8%) (P <.01). Use of assisted reproductive technology to achieve pregnancy
      was significantly lower in the microsurgical redo varicocelectomy group (60.3%)
      than in the control group (84.2%) (P <.01). CONCLUSION: Microsurgical subinguinal
      redo varicocele repair improves postoperative sperm parameters, serum total
      testosterone level, and spontaneous pregnancy rates compared with the controls.
      It also decreases need for use and level of assisted reproductive technology.

PMID- 29649544
TI  - Isolated Right Varicocele and Incidence of Associated Cancer.
AB  - OBJECTIVE: To test the classic teaching that isolated right varicoceles are
      associated with significantly high rates of occult malignancies. METHODS:
      Retrospective chart review included all men diagnosed with varicocele at the
      Cleveland Clinic from 2000 to 2015. Charts were queried for demographics,
      varicocele laterality, cross-sectional imaging, and subsequent diagnosis of
      abdominal malignancy or vascular anomaly. Descriptive statistics are presented as
      means +/- standard deviation. Comparative statistics include analyses of variance
      with Tukey-Kramer pairwise comparisons or chi-square tests as indicated. All P
      <.05 are considered significant. RESULTS: Varicocele was diagnosed in 4060 men
      (3258 left, 337 right, and 465 bilateral). Men with right varicoceles were
      significantly older (43.6 +/- 17.1) than left (33.4 +/- 14.9, P <.0001) or
      bilateral (34.9 +/- 15.3, P <.0001), and had higher body mass indices (right 28.9
      +/- 5.7; left 26.4 +/- 5.5, P <.0001 and; bilateral 26.5 +/- 5.5, P <.0001).
      Laterality of varicocele was not significantly associated with cancer diagnosis
      (P = .313), with cancer diagnosed in 2.67% of right, 1.63% of left, and 2.15% of
      bilateral varicoceles. Rates of abdominal computed tomography imaging differed
      significantly (P <.0001) by laterality: 30.3% of right, 8.7% of left, and 11.2%
      of bilateral varicoceles were scanned. Vascular anomalies did not significantly
      differ by varicocele laterality. CONCLUSION: Men with right varicoceles were
      older, heavier, and underwent more computed tomography scans than those with left
      or bilateral varicoceles but did not have higher rates of cancer diagnosis.

PMID- 29649545
TI  - Complete Primary Repair of Bladder Exstrophy: Critical Analysis of the Long-term
      Outcome.
AB  - OBJECTIVE: To demonstrate the long-term outcome of a contemporary series of 64
      children who underwent complete primary repair of bladder exstrophy (CPRE) in a
      single tertiary referral center. MATERIALS AND METHODS: Between 1998 and 2012, 64
      children, 47 boys and 17 girls, were identified. Only 60 of the 64 cases were
      available for follow-up. The follow-up was done by renal bladder ultrasound and
      serum creatinine every 3 months and voiding cystourethrogram from 6 to 12 months
      postoperatively. Continence was defined as dryness >=3 hours. RESULTS: Median
      (range) follow-up is 14 years (from 5 to 19 years). Voided continence was
      achieved in 14 children (23%) after CPRE only. Additionally, 6 children were
      continent after bladder neck reconstruction (BNR) and 2 after bladder neck
      injection (BNI), raising the percentage of voided continence to 36%. The
      remaining 38 (64%) patients were using clean intermittent catheterization. All
      cases were continent at last assessment. The results of BNR or BNI were better in
      de novo than in redo cases (P <.05). The percentage of cases that needed
      augmentation ileocystoplasty in combination with multiple bladder neck procedures
      was lower in both female and de novo cases (P <.05). CONCLUSION: The percentage
      of children with classic bladder exstrophy who underwent CPRE who will achieve
      continence with volitional voiding via the urethra is 36%. The continence results
      after BNR and BNI are better in de novo cases than in redo ones. Continence in
      female and de novo cases is more likely to be achieved with lower number of
      continence procedures.

PMID- 29649547
TI  - Early onset of disc degeneration in SM/J mice is associated with changes in ion
      transport systems and fibrotic events.
AB  - Intervertebral disc degeneration (IDD) causes back pain and sciatica, affecting
      quality of life and resulting in high economic/social burden. The etiology of IDD
      is not well understood. Along with aging and environmental factors, genetic
      factors also influence the onset, progression and severity of IDD. Genetic
      studies of risk factors for IDD using human cohorts are limited by small sample
      size and low statistical power. Animal models amenable to genetic and functional
      studies of IDD provide desirable alternatives. Despite differences in size and
      cellular content as compared to human intervertebral discs (IVDs), the mouse is a
      powerful model for genetics and assessment of cellular changes relevant to human
      biology. Here, we provide evidence for early onset disc degeneration in SM/J
      relative to LG/J mice with poor and good tissue healing capacity respectively. In
      the first few months of life, LG/J mice maintain a relatively constant pool of
      notochordal-like cells in the nucleus pulposus (NP) of the IVD. In contrast,
      chondrogenic events are observed in SM/J mice beginning as early as one-week-old,
      with progressive fibrotic changes. Further, the extracellular matrix changes in
      the NP are consistent with IVD degeneration. Leveraging on the genomic data of
      two parental and two recombinant inbred lines, we assessed the genetic
      contribution to the NP changes and identified processes linked to the regulation
      of ion transport systems. Significantly, "transport" system is also in the top
      three gene ontology (GO) terms from a comparative proteomic analysis of the mouse
      NP. These findings support the potential of the SM/J, LG/J and their recombinant
      inbred lines for future genetic and biological analysis in mice and validation of
      candidate genes and biological relevance in human cohort studies. The proteomic
      data has been deposited to the ProteomeXchange Consortium via the PRIDE [1]
      partner repository with the dataset identifier PXD008784.

PMID- 29649546
TI  - Pulmonary immunity and extracellular matrix interactions.
AB  - The lung harbors a complex immune system composed of both innate and adaptive
      immune cells. Recognition of infection and injury by receptors on lung innate
      immune cells is crucial for generation of antigen-specific responses by adaptive
      immune cells. The extracellular matrix of the lung, comprising the interstitium
      and basement membrane, plays a key role in the regulation of these immune
      systems. The matrix consists of several hundred assembled proteins that interact
      to form a bioactive scaffold. This template, modified by enzymes, acts to
      facilitate cell function and differentiation and changes dynamically with age and
      lung disease. Herein, we explore relationships between innate and adaptive
      immunity and the lung extracellular matrix. We discuss the interactions between
      extracellular matrix proteins, including glycosaminoglycans, with prominent
      effects on innate immune signaling effectors such as toll-like receptors. We
      describe the relationship of extracellular matrix proteins with adaptive immunity
      and leukocyte migration to sites of injury within the lung. Further study of
      these interactions will lead to greater knowledge of the role of matrix biology
      in lung immunity. The development of novel therapies for acute and chronic lung
      disease is dependent on a comprehensive understanding of these complex matrix
      immunity interactions.

PMID- 29649542
TI  - New approaches for solving old problems in neuronal protein trafficking.
AB  - Fundamental cellular properties are determined by the repertoire and abundance of
      proteins displayed on the cell surface. As such, the trafficking mechanisms for
      establishing and maintaining the surface proteome must be tightly regulated for
      cells to respond appropriately to extracellular cues, yet plastic enough to adapt
      to ever-changing environments. Not only are the identity and abundance of surface
      proteins critical, but in many cases, their regulated spatial positioning within
      surface nanodomains can greatly impact their function. In the context of neuronal
      cell biology, surface levels and positioning of ion channels and neurotransmitter
      receptors play essential roles in establishing important properties, including
      cellular excitability and synaptic strength. Here we review our current
      understanding of the trafficking pathways that control the abundance and
      localization of proteins important for synaptic function and plasticity, as well
      as recent technological advances that are allowing the field to investigate
      protein trafficking with increasing spatiotemporal precision.

PMID- 29649548
TI  - Spontaneous atopic dermatitis due to immune dysregulation in mice lacking Adamts2
      and 14.
AB  - Since its first description, ADAMTS14 has been considered as an aminoprocollagen
      peptidase based on its high similarity with ADAMTS3 and ADAMTS2. As its
      importance for procollagen processing was never experimentally demonstrated in
      vivo, we generated Adamts14-deficient mice. They are healthy, fertile and display
      normal aminoprocollagen processing. They were further crossed with Adamts2
      deficient mice to evaluate potential functional redundancies between these two
      highly related enzymes. Initial characterizations made on young Adamts2-Adamts14
      deficient animals showed the same phenotype as that of Adamts2-deficient mice,
      with no further reduction of procollagen processing and no significant
      aggravation of the structural alterations of collagen fibrils. However, when
      evaluated at older age, Adamts2-Adamts14-deficient mice surprisingly displayed
      epidermal lesions, appearing in 2 month-old males and later in some females, and
      then worsening rapidly. Immunohistological evaluations of skin sections around
      the lesions revealed thickening of the epidermis, hypercellularity in the dermis
      and extensive infiltration by immune cells. Additional investigations, performed
      on young mice before the formation of the initial lesions, revealed that the
      primary cause of the phenotype was not related to alterations of the epidermal
      barrier but was rather the result of an abnormal activation and differentiation
      of T lymphocytes towards a Th1 profile. However, the primary molecular defect
      probably does not reside in the immune system itself since irradiated Adamts2
      Adamts14-deficient mice grafted with WT immune cells still developed lesions.
      While originally created to better characterize the common and specific functions
      of ADAMTS2 and ADAMTS14 in extracellular matrix and connective tissues
      homeostasis, the Adamts2-Adamts14-deficient mice revealed an unexpected but
      significant role of ADAMTS in the regulation of immune system, possibly through a
      cross-talk involving mesenchymal cells and the TGFbeta pathways.

PMID- 29649549
TI  - Bloodstream infections in cancer patients. Risk factors associated with
      mortality.
AB  - OBJECTIVE: The aim of this study was to evaluate the clinical characteristics and
      risk factors associated with mortality in cancer patients with bloodstream
      infections (BSI), analyzing multidrug resistant bacteria (MDR). METHODS: We
      conducted a prospective observational study at a cancer referral center from
      August 2016 to July 2017, which included all BSI. RESULTS: 4220 patients were
      tested with blood cultures; 496 were included. Mean age was 48 years. In 299
      patients with solid tumors, secondary BSI and Central Line-Associated BSI
      (CLABSI) were the most common (55.9% and 31.8%, respectively). In 197 hematologic
      patients, primary and mucosal barrier injury (MBI) BSI were the main type
      (38.6%). Gram-negative were the most frequent bacteria (72.8%), with Escherichia
      coli occupying the first place (n=210, 42.3%), 48% were Extended-Spectrum Beta
      Lactamase (ESBL) producers, and 1.8% were resistant to carbapenems. Mortality at
      day 30, was 22%, but reached 70% when patients did not receive an appropriate
      antimicrobial treatment. Multivariate analysis showed that progression or relapse
      of the oncologic disease, inappropriate antimicrobial treatment, and having
      resistant bacteria were independently associated with 30-day mortality.
      CONCLUSIONS: Emergence of MDR bacteria is an important healthcare problem
      worldwide. Patients with BSI, particularly those patients with MDR bacteria have
      a higher mortality risk.

PMID- 29649550
TI  - Healthcare worker exposure to Middle East respiratory syndrome coronavirus (MERS
      CoV): Revision of screening strategies urgently needed.
AB  - OBJECTIVES: Middle East respiratory syndrome coronavirus (MERS-CoV) continues to
      cause frequent hospital outbreaks in Saudi Arabia, with emergency departments as
      the initial site of the spread of this virus. METHODS: The risk of transmission
      of MERS-CoV infection to healthcare workers (HCWs) was assessed in an outbreak in
      Riyadh. All HCWs with unprotected exposure to confirmed cases were tested after
      24h of exposure. Two negative results for MERS-CoV obtained 3days apart and being
      free of any suggestive signs and symptoms were used to end the isolation of the
      HCWs and allow their return to duty. RESULTS: Overall 17 out of 879 HCWS with
      different levels of exposure tested positive for MERS-CoV. Of the 15 positive
      HCWS with adequate follow-up, 40% (6/15 HCWs) tested positive on the first
      sampling and 53% (8/15) tested positive on the second sampling. The time to
      negative results among the 15 positive HCWs ranged between 4 and 47days (average
      14.5 days) and the infected HCWs needed on average two samples for clearance. All
      positive HCWs were either asymptomatic or had mild disease. CONCLUSIONS: The data
      obtained in this study support the widespread testing of all close contacts of
      MERS-CoV cases, regardless of the significance of the contact or presence or
      absence of symptoms. In addition, urgent careful review of guidance regarding the
      return of asymptomatic MERS-CoV-positive HCWs under investigation to active duty
      is needed.

PMID- 29649551
TI  - The receptor for activated C kinase 1 (RACK1) mediating immune response in thick
      shell mussel Mytilus coruscus.
AB  - The receptor for activated C kinase 1 (RACK1) is a intracellular receptor for the
      protein kinase C family which mediates various biological processes. Here, a
      novel RACK1 gene termed Mc-RACK1 was identified from thick shell mussel, Mytilus
      coruscus. Mc-RACK1 shared typical RACK1 domains containing WD repeats, PKC
      phosphorylation sites, N-myristoylation sites, PKC activation sites, TK
      phosphorylation site and WD motifs. Mc-RACK1 was constitutively expressed in all
      examined tissues, and its expression in gills, haemocytes and digestive glands
      were significantly up-regulated upon LPS challenge. Mc-RACK1 showed a
      significantly down-regulated expression in gills and haemocytes at the early
      phase upon copper exposure. Mc-RACK1 in haemocytes was silenced after receiving
      its dsRNA, meanwhile, the increases of SOD and CAT activity were investigated.
      Further, Mc-RACK1 could activate the NF-kappaB and ISRE reporter in HEK-293T
      cells. These suggested that Mc-RACK1 had a deeper involvement in mollusc
      immunity, and played an important role in antioxidant system.

PMID- 29649552
TI  - The Florida manatee (Trichechus manatus latirostris) T cell receptor loci exhibit
      V subgroup synteny and chain-specific evolution.
AB  - The Florida manatee (Trichechus manatus latirostris) has limited diversity in the
      immunoglobulin heavy chain. We therefore investigated the antigen receptor loci
      of the other arm of the adaptive immune system: the T cell receptor. Manatees are
      the first species from Afrotheria, a basal eutherian superorder, to have an in
      depth characterization of all T cell receptor loci. By annotating the genome and
      expressed transcripts, we found that each chain has distinct features that
      correlates to their individual functions. The genomic organization also plays a
      role in modulating sequence conservation between species. There were extensive V
      subgroup synteny blocks in the TRA and TRB loci between T. m. latirostris and
      human. Increased genomic locus complexity correlated to increased locus synteny.
      We also identified evidence for a VHD pseudogene for the first time in a
      eutherian mammal. These findings emphasize the value of including species within
      this basal eutherian radiation in comparative studies.

PMID- 29649554
TI  - Persistence of meticillin-resistant Staphylococcus aureus carriage in re-admitted
      patients.
AB  - A retrospective cohort study was conducted to investigate the duration and risk
      factors for persistence of meticillin-resistant Staphylococcus aureus (MRSA)
      colonization among known carriers who were re-admitted to hospital. MRSA carriage
      persisted in a high proportion of known carriers up to two years after their last
      date of discharge, and re-admission screening should be performed for at least
      this duration. A targeted screening approach should focus on older patients with
      a history of long inpatient stays, who are at higher risk of persistent carriage.
      Timely discharge planning is important in reducing the risk of persistent MRSA
      colonization among known carriers.

PMID- 29649555
TI  - Paradoxical Acinetobacter-associated ventilator-associated pneumonia incidence
      rates within prevention studies using respiratory tract applications of topical
      polymyxin: benchmarking the evidence base.
AB  - BACKGROUND: Regimens containing topical polymyxin appear to be more effective in
      preventing ventilator-associated pneumonia (VAP) than other methods. AIM: To
      benchmark the incidence rates of Acinetobacter-associated VAP (AAVAP) within
      component (control and intervention) groups from concurrent controlled studies of
      polymyxin compared with studies of various VAP prevention methods other than
      polymyxin (non-polymyxin studies). METHODS: An AAVAP benchmark was derived using
      data from 77 observational groups without any VAP prevention method under study.
      Data from 41 non-polymyxin studies provided additional points of reference. The
      benchmarking was undertaken by meta-regression using generalized estimating
      equation methods. RESULTS: Within 20 studies of topical polymyxin, the mean AAVAP
      was 4.6% [95% confidence interval (CI) 3.0-6.9] and 3.7% (95% CI 2.0-5.3) for
      control and intervention groups, respectively. In contrast, the AAVAP benchmark
      was 1.5% (95% CI 1.2-2.0). In the AAVAP meta-regression model, group origin from
      a trauma intensive care unit (+0.55; +0.16 to +0.94, P = 0.006) or membership of
      a polymyxin control group (+0.64; +0.21 to +1.31, P = 0.023), but not membership
      of a polymyxin intervention group (+0.24; -0.37 to +0.84, P = 0.45), were
      significant positive correlates. CONCLUSIONS: The mean incidence of AAVAP within
      the control groups of studies of topical polymyxin is more than double the
      benchmark, whereas the incidence rates within the groups of non-polymyxin studies
      and, paradoxically, polymyxin intervention groups are more similar to the
      benchmark. These incidence rates, which are paradoxical in the context of an
      apparent effect against VAP within controlled trials of topical polymyxin-based
      interventions, force a re-appraisal.

PMID- 29649556
TI  - Is there an association between airborne and surface microbes in the critical
      care environment?
AB  - BACKGROUND: There are few data and no accepted standards for air quality in the
      intensive care unit (ICU). Any relationship between airborne pathogens and
      hospital-acquired infection (HAI) risk in the ICU remains unknown. AIM: First, to
      correlate environmental contamination of air and surfaces in the ICU; second, to
      examine any association between environmental contamination and ICU-acquired
      staphylococcal infection. METHODS: Patients, air, and surfaces were screened on
      10 sampling days in a mechanically ventilated 10-bed ICU for a 10-month period.
      Near-patient hand-touch sites (N = 500) and air (N = 80) were screened for total
      colony count and Staphylococcus aureus. Air counts were compared with surface
      counts according to proposed standards for air and surface bioburden. Patients
      were monitored for ICU-acquired staphylococcal infection throughout. FINDINGS:
      Overall, 235 of 500 (47%) surfaces failed the standard for aerobic counts (<=2.5
      cfu/cm2). Half of passive air samples (20/40: 50%) failed the 'index of microbial
      air' contamination (2 cfu/9 cm plate/h), and 15/40 (37.5%) active air samples
      failed the clean air standard (<10 cfu/m3). Settle plate data were closer to the
      pass/fail proportion from surfaces and provided the best agreement between air
      parameters and surfaces when evaluating surface benchmark values of 0-20 cfu/cm2.
      The surface standard most likely to reflect hygiene pass/fail results compared
      with air was 5 cfu/cm2. Rates of ICU-acquired staphylococcal infection were
      associated with surface counts per bed during 72h encompassing sampling days (P =
      0.012). CONCLUSION: Passive air sampling provides quantitative data analogous to
      that obtained from surfaces. Settle plates could serve as a proxy for routine
      environmental screening to determine the infection risk in ICU.

PMID- 29649553
TI  - The interplay between dose and immune system activation determines fungal
      infection outcome in the African malaria mosquito, Anopheles gambiae.
AB  - The Toll pathway is a central regulator of antifungal immunity in insects. In
      mosquitoes, the Toll pathway affects infections with the fungal entomopathogen,
      Beauveria bassiana, which is considered a potential mosquito biopesticide. We
      report here the use of B. bassiana strain I93-825 in Anopheles gambiae to analyze
      the impact of Toll pathway modulation on mosquito survival. Exposure to a narrow
      dose range of conidia by direct contact decreased mosquito longevity and median
      survival. In addition, fungal exposure dose correlated positively and linearly
      with hazard ratio. Increased Toll signaling by knockdown of its inhibitor,
      cactus, decreased survivorship of uninfected females, increased mosquito survival
      after low dose B. bassiana exposure, but had little effect following exposure to
      higher doses. This observed trade-off could have implications for development of
      B. bassiana as a prospective vector control tool. On the one hand, selection for
      small increases in mosquito immune signaling across a narrow dose range could
      impair efficacy of B. bassiana. On the other hand, costs of immunity and the
      capacity for higher doses of fungus to overwhelm immune responses could limit
      evolution of resistance.

PMID- 29649557
TI  - Ultraviolet-C decontamination of hand-held tablet devices in the healthcare
      environment using the Codonics D6000TM disinfection system.
AB  - Mobile phones and tablet computers may be contaminated with micro-organisms and
      become a potential reservoir for cross-transmission of pathogens between
      healthcare workers and patients. There is no generally accepted guidance on how
      to reduce contamination on mobile devices in healthcare settings. Our aim was to
      determine the efficacy of the Codonics D6000TM UV-C disinfection device. Daily
      disinfection reduced contamination on screens and on protective cases (test)
      significantly, but not all cases (control) could be decontaminated. The median
      aerobic colony count on the control and the test cases was 52 cfu/25 cm2
      (interquartile range: 33-89) and 22 cfu/25 cm2 (10.5-41), respectively, before
      disinfection.

PMID- 29649558
TI  - Feasibility of a real-time hand hygiene notification machine learning system in
      outpatient clinics.
AB  - BACKGROUND: Various technologies have been developed to improve hand hygiene (HH)
      compliance in inpatient settings; however, little is known about the feasibility
      of machine learning technology for this purpose in outpatient clinics. AIM: To
      assess the effectiveness, user experiences, and costs of implementing a real-time
      HH notification machine learning system in outpatient clinics. METHODS: In our
      mixed methods study, a multi-disciplinary team co-created an infrared guided
      sensor system to automatically notify clinicians to perform HH just before first
      patient contact. Notification technology effects were measured by comparing HH
      compliance at baseline (without notifications) with real-time auditory
      notifications that continued till HH was performed (intervention I) or
      notifications lasting 15 s (intervention II). User experiences were collected
      during daily briefings and semi-structured interviews. Costs of implementation of
      the system were calculated and compared to the current observational auditing
      programme. FINDINGS: Average baseline HH performance before first patient contact
      was 53.8%. With real-time auditory notifications that continued till HH was
      performed, overall HH performance increased to 100% (P < 0.001). With auditory
      notifications of a maximum duration of 15 s, HH performance was 80.4% (P <
      0.001). Users emphasized the relevance of real-time notification and contributed
      to technical feasibility improvements that were implemented in the prototype.
      Annual running costs for the machine learning system were estimated to be 46%
      lower than the observational auditing programme. CONCLUSION: Machine learning
      technology that enables real-time HH notification provides a promising cost
      effective approach to both improving and monitoring HH, and deserves further
      development in outpatient settings.

PMID- 29649559
TI  - Ultrafast Doppler for neonatal brain imaging.
AB  - The emergence of functional neuroimaging has dramatically accelerated our
      understanding of the human mind. The advent of functional Magnetic Resonance
      Imaging paved the way for the next decades' major discoveries in neuroscience and
      today remains the "gold standard" for deep brain imaging. Recent improvements in
      imaging technology have been somewhat limited to incremental innovations of
      mature techniques instead of breakthroughs. Recently, the use of ultrasonic plane
      waves transmitted at ultrafast frame rates was shown to highly increase Doppler
      ultrasound sensitivity to blood flows in small vessels in rodents. By identifying
      regions of brain activation through neurovascular coupling, Ultrafast Doppler was
      entering into the world of preclinical neuroimaging. The combination of many
      advantages, including high spatio-temporal resolution, deep penetration, high
      sensitivity and portability provided unique information about brain function.
      Recently, Ultrafast Doppler imaging was found able to non-invasively image the
      spatial and temporal dynamics of microvascular changes during seizures and
      interictal periods with an unprecedented resolution at bedside. This review
      summarizes the technical basis, the added value and the clinical perspectives
      provided by this new brain imaging modality that could create a breakthrough in
      the knowledge of brain hemodynamics, brain insult, and neuroprotection.

PMID- 29649561
TI  - Real-motion signals in human early visual cortex.
AB  - Eye movements induce visual motion that can complicate the stable perception of
      the world. The visual system compensates for such self-induced visual motion by
      integrating visual input with efference copies of eye movement commands. This
      mechanism is central as it does not only support perceptual stability but also
      mediates reliable perception of world-centered objective motion. In humans, it
      remains elusive whether visual motion responses in early retinotopic cortex are
      driven by objective motion or by retinal motion associated with it. To address
      this question, we used fMRI to examine functional responses of sixteen visual
      areas to combinations of planar objective motion and pursuit eye movements.
      Observers were exposed to objective motion that was faster, matched or slower
      relative to pursuit, allowing us to compare conditions that differed in objective
      motion velocity while retinal motion and eye movement signals were matched. Our
      results show that not only higher level motion regions such as V3A and V6, but
      also early visual areas signaled the velocity of objective motion, hence the
      product of integrating retinal with non-retinal signals. These results shed new
      light on mechanisms that mediate perceptual stability and real-motion perception,
      and show that extra-retinal signals related to pursuit eye movements influence
      processing in human early visual cortex.

PMID- 29649560
TI  - Network specialization during adolescence: Hippocampal effective connectivity in
      boys and girls.
AB  - Adolescence is a complex period of concurrent mental and physical development
      that facilitates adult functioning at multiple levels. Despite the growing number
      of neuroimaging studies of cognitive development in adolescence focusing on
      regional activation patterns, there remains a paucity of information about the
      functional interactions across these participating regions that are critical for
      cognitive functioning, including memory. The current study used structural
      equation modeling (SEM) to determine how interactions among brain regions
      critical for memory change over the course of adolescence. We obtained functional
      MRI in 77 individuals aged 8-16 years old, divided into younger (ages 8-10) and
      older (ages > 11) cohorts, using an incidental encoding memory task to activate
      hippocampus formation and associated brain networks, as well as behavioral data
      on memory function. SEM was performed on the imaging data for four groups
      (younger girls, younger boys, older girls, and older boys) that were subsequently
      compared using a stacked model approach. Significant differences were seen
      between the models for these groups. Younger boys had a predominantly posterior
      distribution of connections originating in primary visual regions and terminating
      on multi-modal processing regions. In older boys, there was a relatively greater
      anterior connection distribution, with increased effective connectivity within
      association and multi-modal processing regions. Connection patterns in younger
      girls were similar to those of older boys, with a generally anterior-posterior
      distributed network among sensory, multi-modal, and limbic regions. In contrast,
      connections in older girls were widely distributed but relatively weaker. Memory
      performance increased with age, without a significant difference between the
      sexes. These findings suggest a progressive reorganization among brain regions,
      with a commensurate increase in efficiency of cognitive functioning, from younger
      to older individuals in both girls and boys, providing insight into the age- and
      gender-specific processes at play during this critical transition period.

PMID- 29649562
TI  - Carrying the past to the future: Distinct brain networks underlie individual
      differences in human spatial working memory capacity.
AB  - Spatial working memory (SWM) relies on the interplay of anatomically separated
      and interconnected large-scale brain networks. EEG studies often observe load
      associated sustained negative activity during SWM retention. Yet, whether and how
      such sustained negative activity in retention relates to network-specific
      functional activation/deactivation and relates to individual differences in SWM
      capacity remain to be elucidated. To cover these gaps, we recorded concurrent EEG
      fMRI data in 70 healthy young adults during the Sternberg delayed-match-to-sample
      SWM task with three memory load levels. To a subset of participants (N = 28) that
      performed the task properly and had artefact-free fMRI and EEG data, we employed
      a novel temporo-spatial principal component analysis to derive load-dependent
      negative slow wave (NSW) from retention-related event-related potentials. The
      associations between NSW responses with SWM capacity were divergent in the higher
      (N = 14) and lower (N = 14) SWM capacity groups. Specifically, larger load
      related increase in NSW amplitude was associated with greater SWM capacity for
      the higher capacity group but lower SWM capacity for the lower capacity group.
      Furthermore, for the higher capacity group, larger NSW amplitude was related to
      greater activation in bilateral parietal areas of the fronto-parietal network
      (FPN) and greater deactivation in medial frontal gyrus and posterior mid
      cingulate cortex of the default mode network (DMN) during retention. In contrast,
      the lower capacity group did not show similar pattern. Instead, greater NSW was
      linked to higher deactivation in right posterior middle temporal gyrus. Our
      findings shed light on the possible differential EEG-informed neural network
      mechanism during memory maintenance underlying individual differences in SWM
      capacity.

PMID- 29649563
TI  - Isolation and characterization of a novel serine protease inhibitor, SjSPI, from
      Schistosoma japonicum.
AB  - Serine proteinase inhibitor (Serpin, SPI) is a vital superfamily of endogenous
      inhibitors that monitor proteolytic events active in a number of biological
      functions. In this study, we isolated a full length gene encoding a novel serine
      protease inhibitor of Schistosoma japonicum (SjSPI) and characterized its
      molecular properties. Our result showed that SjSPI contained an open reading
      frame of 1,218 bp, which encoded 405 amino acid residues. Chromosomal structure
      analysis showed that SjSPI gene was comprised of six exons separated by five
      introns. It had essential structural motifs which were well conserved among the
      Serpin superfamily and showed 17-33% sequence identities with Serpins from other
      helminthic parasites. Trematode Serpin diverged separately into two different
      subclades and that the SjSPI clustered Subclade I. Exon-intron structures of
      trematode Serpins were highly conserved, closely with cestode Serpins. No signal
      peptide but a strongly transmembrane domain was predicted to exist in SjSPI,
      suggesting that the protein might be a soluble membrane-associated protein.
      Homology modeling predicted in silico confirmed that the SjSPI structure also
      belonged to the Serpin superfamily, containing nine alpha-helices and a reactive
      central loop. The bacterially expressed recombinant GST-SjSPI protein effectively
      inhibited the activities of chymotrypsin, trypsin and thrombin. Expression of
      SjSPI was detected throughout various developmental stages of the parasite in
      host and reached its maximal levels at the adult and egg stages, which suggests
      that SjSPI may be possibly involved in maintaining the physiology of eggs by
      regulating endogenous serine proteases.

PMID- 29649564
TI  - XBP1 activation enhances MANF expression via binding to endoplasmic reticulum
      stress response elements within MANF promoter region in hepatitis B.
AB  - As an endoplasmic reticulum (ER) stress-related protein, mesencephalic astrocyte
      derived neurotrophic factor (MANF) is involved in inflammatory diseases, such as
      rheumatoid arthritis. However, the mechanisms of the transcriptional regulation
      of MANF is still undefined. Here, we showed that MANF expression was upregulated
      in hepatitis B tissues and hepatoma cells, and positively correlated with the
      spliced X-box binding protein-1 (XBP1s). Both overexpression of XBP1s and
      tunicamycin treatment were able to enhance MANF transcription. On the contrary,
      inhibition of XBP1 splicing by IRE1alpha endonuclease inhibitor or knockdown of
      XBP1s with siRNA attenuated MANF expression. Two ER stress-responsive elements
      (ERSE) were found in the promoter region of MANF (ERSE I and ERSE II). The
      chromatin immunoprecipitation and reporter gene assay showed that XBP1s mainly
      binds to ERSE I to promote MANF transcription. Moreover, MANF was found to
      interact with XBP1s to enhance its own expression. Our findings uncover a new
      mechanism of ERSE-dependent transcriptional regulation of MANF, as well as a key
      role of XBP1s in promoting the MANF expression.

PMID- 29649565
TI  - Polyamines protect nucleic acids against depurination.
AB  - Depurination is accelerated by heat and reactive oxygen species under
      physiological conditions. We previously reported that polyamines are involved in
      mitigation of heat shock and oxidative stresses through stimulation of the
      synthesis of heat shock and antioxidant proteins. This time, we investigated
      whether polyamines are directly involved in protecting nucleic acids from thermal
      depurination induced by high temperature. The suppressing efficiencies of
      depurination of DNA by spermine, caldopentamine and caldohexamine in the presence
      of 1 mM Mg2+, were approximately 50%, 60% and 80%, respectively. Mg2+ also
      protected nucleic acids against depurination but to a lesser degree than
      polyamines. Longer unusual polyamines were more effective at protecting DNA
      against depurination compared to standard polyamines. The tRNA depurination
      suppressing efficiencies of spermine, caldopentamine and caldohexamine in the
      presence of 1 mM Mg2+, were approximately 60%, 70% and 80%, respectively.
      Standard polyamines protected tRNA and ribosomes more effectively than DNA
      against thermal depurination. Branched polyamines such as mitsubishine and
      tetrakis(3-aminopropyl)ammonium also protected RNA more effectively than DNA
      against depurination. These results suggest that the suppressing effect of
      depurination of nucleic acids (DNA and RNA) depends on the types of polyamines:
      i.e. to maintain functional conformation of nucleic acids at high temperature,
      longer and branched polyamines play important roles in protecting nucleic acids
      from depurination compared to standard polyamines and Mg2+.

PMID- 29649566
TI  - Spatio-temporal monitoring of lipid peroxyl radicals in live cell studies
      combining fluorogenic antioxidants and fluorescence microscopy methods.
AB  - Lipid peroxidation of polyunsaturated fatty acids in cells may occur via their
      catalytic autoxidation through peroxyl radicals under oxidative stress
      conditions. Lipid peroxidation is related to a number of pathologies, and may be
      invoked in new forms of regulated cell death, yet it may also have beneficial
      roles in cell signaling cascades. Antioxidants are a natural line of defense
      against lipid peroxidation, and may accordingly impact the biological outcome
      associated with the redox chemistry of lipid peroxidation. Critical to unraveling
      the physiological and pathological role of lipid peroxidation is the development
      of novel probes with the partition, chemical sensitivity and more importantly,
      molecular specificity, enabling the spatial and temporal imaging of peroxyl
      radicals in the lipid membranes of live cells, reporting on the redox status of
      the cell membrane. This review describes our recent progress to visualize lipid
      peroxidation in model membrane systems and in live cell studies. Our work
      portrays the mechanistic insight leading to the development of a highly sensitive
      probe to monitor lipid peroxyl radicals (LOO*). It also describes technical
      aspects including reagents and fluorescence microscopy methodologies to consider
      in order to achieve the much sought after monitoring of rates of lipid peroxyl
      radical production in live cell studies, be it under oxidative stress but also
      under cell homeostasis. This review seeks to bring attention to the study of
      lipid redox reactions and to lay the groundwork for the adoption of fluorogenic
      antioxidant probeshancement and maximum intensity recorded in turn provide a
      benchmark to estimate, when compared to the control BODIPY dye lacking the
      intramolecular PeT based switch, the overall exte and related fluorescence
      microscopy methods toward gaining rich spatiotemporal information on lipid
      peroxidation in live cells.

PMID- 29649567
TI  - Nrf2 signaling and autophagy are complementary in protecting breast cancer cells
      during glucose deprivation.
AB  - Autophagy can serve as a mechanism for survival of cells during nutrient
      deprivation by recycling cellular macromolecules and organelles transiently to
      provide essential metabolic substrates. However, autophagy itself causes
      metabolic stress to cells, and other cellular protective mechanisms likely
      cooperate with autophagy to promote cell survival during nutrient deprivation. In
      this study, we explored protective mechanisms in breast cancer cells in the
      setting of glucose deprivation. While breast cancer cells (MCF7 and T47D) survive
      in glucose-free medium for three days or more, autophagy is induced in this
      setting. Blocking autophagy pharmacologically with chloroquine or by knock-out of
      an essential autophagy gene, such as Beclin 1 or ATG7, markedly reduces the
      ability of cells to survive during glucose deprivation. Autophagy previously was
      shown to degrade p62, a protein that sequesters KEAP1, and KEAP1 in turn
      sequesters Nrf2, a master regulator of the antioxidant response. Hence, we
      investigated how the Nrf2 signaling pathway might be affected by glucose
      deprivation and autophagy. We found that while glucose deprivation does cause
      decreased cellular levels of p62, Nrf2 protein levels and activity unexpectedly
      increase in this setting. Moreover, this increase in Nrf2 activity provides
      important protection to breast cancer cells during glucose deprivation, since
      siRNA knockdown of Nrf2 markedly impairs survival during glucose deprivation.
      Antioxidants, N-acetyl cysteine and glutathione also protect these cells during
      glucose deprivation, leading us to conclude that Nrf2 signaling via its
      antioxidant activity has a critical and previously undescribed role of protecting
      cells during glucose deprivation-induced autophagy.

PMID- 29649568
TI  - Honokiol alleviates the degeneration of intervertebral disc via suppressing the
      activation of TXNIP-NLRP3 inflammasome signal pathway.
AB  - Intervertebral disc degeneration (IVDD) is a multifactorial disease and
      responsible for many spine related disorders, causes disability in the workforce
      and heavy social costs all over the world. Honokiol, a low molecular weight
      natural product, could penetrate into and distribute in IVDs to achieve
      therapeutic effect in a rat tail model. Therefore, the present study was
      undertaken to examine the antiinflammatory, antioxidation and IVD-protective
      effect of honokiol using nucleus pulposus cells and investigate its mechanisms to
      provide a new basis for future clinical treatment of IVDD. In the current study,
      we demonstrated that honokiol inhibits the H2O2-induced apoptosis (caspase-9,
      caspase-3, and bax), levels of oxidative stress mediators (ROS, MDA), expression
      of inflammatory mediators (Interleukin-6, COX-2, and iNOS), major matrix
      degrading proteases (MMP-3, MMP-13, ADAMTS5, and ADAMTS4) associated with nucleus
      pulposus degradation. Furthermore, we found nucleus pulposus protective ability
      of honokiol by up-regulating extra cellular matrix anabolic factors like type II
      collagen (Col II) and SOX9 in nucleus pulposus. We also found that honokiol
      suppressed the phosphorylation of NF-kB and JNK, and activation of TXNIP-NLRP3
      inflammasome in H2O2-stimulated nucleus pulposus cells, thereby inhibiting the
      activation of downstream inflammatory mediators such as Interleukin-1beta.
      Furthermore, honokiol showed a cartilage protective effect in the progression of
      IVDD in a rat model induced by puncture. Thus, our results demonstrate that
      honokiol inhibited the H2O2 induced apoptosis, oxidative stress, and inflammatory
      responses through the depression of TXNIP/NLRP3/caspase-1/ Interleukin - 1beta
      signaling axis and the activation of NF-kB and JNK. Honokiol possess nucleus
      pulposus protective properties and may be of value in suppressing the
      pathogenesis of IVDD.

PMID- 29649569
TI  - The use of molecular descriptors in the development of co-amorphous formulations.
AB  - Co-amorphous systems consisting of a drug and an amino acid have been
      investigated extensively for the enhancement of drug solubility and amorphous
      stability. The purpose of this study is to investigate which molecular
      descriptors are important for predicting the likelihood of a successful co
      amorphisation between amino acid and drug. The predictions are thought to be used
      in an early screening phase to identify potential drug-amino acid combinations
      for further studies. A large variety of molecular descriptors was calculated for
      six drugs (carvedilol, mebendazole, carbamazepine, furosemide, indomethacin and
      simvastatin) and the twenty naturally occurring amino acids. The descriptor
      differences for all drug-amino acid combinations were calculated and used as
      input in the X-matrix of a Partial Least Square Discriminant Analysis (PLS-DA).
      The Y-matrix of the PLS-DA consisted of the X-ray powder diffraction response
      ("co-amorphous" or "not co-amorphous") obtained by ball milling all combinations
      for 60 min. The PLS-DA model showed a clear separation of the not co-amorphous
      and the co-amorphous samples and was successfully predicting the class membership
      of 19 out of the 20 completely left out drug-amino acid combinations of
      mebendazole. The approach seems to be promising for predicting the ability of new
      drug-amino acids combinations to become co-amorphous.

PMID- 29649570
TI  - Effect of amino acids on the stability of spray freeze-dried immunoglobulin G in
      sugar-based matrices.
AB  - The purpose of this study was to prepare spray freeze-dried particles of
      immunoglobulin G (IgG) using various combinations of trehalose and different
      amino acids (leucine, phenylalanine, arginine, cysteine, and glycine), and
      investigate the effect of the amino acids on the stability of IgG during the
      spray freeze-drying (SFD) process and storage. The morphology and structural
      integrity of the processed particles were evaluated by physical and spectroscopic
      techniques. SFD-processed IgG without any excipient resulted in the formation of
      aggregates corresponding to approximately 14% of IgG. In contrast, IgG
      formulations stabilized using an optimal level of leucine, phenylalanine, or
      glycine in the presence of trehalose displayed aggregates <2.2%. In particular,
      phenylalanine combined with trehalose was most effective in stabilizing IgG
      against shear, freezing, and dehydration stresses during SFD. Arginine and
      cysteine were destabilizers displaying aggregation and fragmentation of IgG,
      respectively. Aggregation and fragmentation were evaluated by dynamic light
      scattering, ultraviolet spectrophotometry, size-exclusion chromatography, and
      microchip capillary gel electrophoresis. The IgG formulations prepared with
      leucine, phenylalanine, or glycine in the presence of trehalose showed good
      stability after storage at 40  degrees C and 75% relative humidity for 2 months.
      Thus, a combination of the excipients trehalose and uncharged, nonpolar amino
      acids appears effective for production of stable SFD IgG formulations.

PMID- 29649571
TI  - Spermidine ameliorates the neuronal aging by improving the mitochondrial function
      in vitro.
AB  - Changes in mitochondrial structure and function are the initial factors of cell
      aging. Spermidine has an antiaging effect, but its effect on neuronal aging and
      mitochondrial mechanisms is unclear. In this study, mouse neuroblastoma (N2a)
      cells were treated with d-galactose (d-Gal) to establish cell aging to
      investigate the antiaging effect and mechanisms of spermidine. Changes in the
      cell cycle and beta-galactosidase activity were analyzed to evaluate the extent
      of cell aging. Stabilities of mitochondrial mRNA and mitochondrial membrane
      potential (MMP) were evaluated in the process of cell aging under different
      treatments. The mitochondrial function was also evaluated using the Seahorse
      Metabolic Analysis System combined with ATP production. The unfolded protein
      response (UPR) of the N2a cells was analyzed under different treatments. Results
      showed that spermidine pretreatment could delay the cell aging and could maintain
      the mitochondrial stability during d-Gal treatment. Spermidine increased the
      proportion of cells in the S phase and maintained the MMP. The oxygen utilization
      and ATP production in the N2a cells were reduced by d-Gal treatment but were
      partially rescued by the spermidine pretreatment. Spermidine ameliorated the N2a
      cell aging by promoting the autophagy and inhibiting the apoptosis except the
      UPR. These results showed that spermidine could ameliorate the N2a cell aging by
      maintaining the mitochondrial mRNA transcription, MMP and oxygen utilization
      during the d-Gal treatment.

PMID- 29649572
TI  - Associations of sarcopenic obesity with the metabolic syndrome and insulin
      resistance over five years in older men: The Concord Health and Ageing in Men
      Project.
AB  - PURPOSE: Previous cross-sectional studies investigating associations of
      sarcopenic obesity with metabolic syndrome (MetS) and insulin resistance have not
      utilised consensus definitions of sarcopenia. We aimed to determine associations
      of sarcopenic obesity with MetS and insulin resistance over five years in
      community-dwelling older men. METHODS: 1231 men aged >=70 years had appendicular
      lean mass (ALM) and body fat percentage assessed by dual-energy X-ray
      absorptiometry and hand grip strength and gait speed tests. Sarcopenia was
      defined as low ALM/height (m2) and low hand grip strength or gait speed (European
      Working Group definition); obesity was defined as body fat percentage >=30%. MetS
      was assessed at baseline and 5-years later. Homeostasis Model Assessment of
      Insulin Resistance (HOMA-IR) was assessed at 5-years only. RESULTS: Men with
      sarcopenic obesity (odds ratio, 95% CI: 2.07, 1.21-3.55) and non-sarcopenic
      obesity (4.19, 3.16-5.57) had higher MetS likelihood than those with non
      sarcopenic non-obesity at baseline. Higher gait speed predicted lower odds for
      prevalent MetS (0.45, 0.21-0.96 per m/s). Higher body fat predicted increased
      odds for prevalent and incident MetS (1.14, 1.11-1.17 and 1.11, 1.02-1.20 per kg,
      respectively) and deleterious 5-year changes in MetS fasting glucose, high
      density lipoprotein cholesterol and triglycerides (all P < 0.05). Compared with
      non-sarcopenic non-obesity, estimated marginal means for HOMA-IR at 5-years were
      higher in non-sarcopenic obesity only (1.0, 0.8-1.1 vs 1.3, 1.2-1.5; P < 0.001).
      Similar results were observed when sarcopenic obesity was defined by waist
      circumference. CONCLUSIONS: Sarcopenic obesity does not appear to confer greater
      risk for incident MetS or insulin resistance than obesity alone in community
      dwelling older men.

PMID- 29649573
TI  - An operational model for GPCR homodimers and its application in the analysis of
      biased signaling.
AB  - G-protein-coupled receptors are one of the most important protein superfamilies
      as drug targets in drug discovery programs. Their interactions with ligands are
      influenced by their homomerization. In this study, we propose an operational
      model for receptor homodimers, which includes constitutive receptor activity.
      Distinct functional response curves can be obtained from this model, which can
      satisfactorily depict typical complex experimental data as biphasic and bell
      shaped curves. Operational parameters in the model can provide mechanistic
      explanations for observed functional complexity associated with the cooperativity
      and intrinsic efficacy of ligands. Because the model presented here is derived
      from the conceptual framework of operational models, it takes advantage of the
      body of knowledge coming from the widespread use of this type of modeling. The
      operational homodimer model can also explain the biased signaling dependent on
      ligand concentration. In conclusion, this operational homodimer model has a wide
      range of applications in pharmacological research.

PMID- 29649574
TI  - Detection of high GS risk group prostate tumors by diffusion tensor imaging and
      logistic regression modelling.
AB  - PURPOSE: To assess the value of joint evaluation of diffusion tensor imaging
      (DTI) measures by using logistic regression modelling to detect high GS risk
      group prostate tumors. MATERIALS AND METHODS: Fifty tumors imaged using DTI on a
      3 T MRI device were analyzed. Regions of interests focusing on the center of
      tumor foci and noncancerous tissue on the maps of mean diffusivity (MD) and
      fractional anisotropy (FA) were used to extract the minimum, the maximum and the
      mean measures. Measure ratio was computed by dividing tumor measure by
      noncancerous tissue measure. Logistic regression models were fitted for all
      possible pair combinations of the measures using 5-fold cross validation.
      RESULTS: Systematic differences are present for all MD measures and also for all
      FA measures in distinguishing the high risk tumors [GS >= 7(4 + 3)] from the low
      risk tumors [GS <= 7(3 + 4)] (P < 0.05). Smaller value for MD measures and larger
      value for FA measures indicate the high risk. The models enrolling the measures
      achieve good fits and good classification performances (R2adj = 0.55-0.60, AUC =
      0.88-0.91), however the models using the measure ratios perform better (R2adj =
      0.59-0.75, AUC = 0.88-0.95). The model that employs the ratios of minimum MD and
      maximum FA accomplishes the highest sensitivity, specificity and accuracy (Se =
      77.8%, Sp = 96.9% and Acc = 90.0%). CONCLUSION: Joint evaluation of MD and FA
      diffusion tensor imaging measures is valuable to detect high GS risk group
      peripheral zone prostate tumors. However, use of the ratios of the measures
      improves the accuracy of the detections substantially. Logistic regression
      modelling provides a favorable solution for the joint evaluations easily
      adoptable in clinical practice.

PMID- 29649575
TI  - The interaction between environmental triggers and epigenetics in autoimmunity.
AB  - Systemic lupus erythematosus flares when genetically predisposed people encounter
      environmental agents that cause oxidative stress, such as infections and
      sunlight. How these modify the immune system to initiate flares is unclear. Drug
      induced lupus models demonstrate that CD4+ T cells epigenetically altered with
      DNA methylation inhibitors cause lupus in animal models, and similar T cells are
      found in patients with active lupus. How infections and sun exposure inhibit T
      cell DNA methylation is unclear. DNA methylation patterns are replicated each
      time a cell divides in a process that requires DNA methyltransferase one (Dnmt1),
      which is upregulated as cells enter mitosis, as well as the methyl donor S
      adenosylmethionine, created from dietary sources. Reactive oxygen species that
      inhibit Dnmt1 upregulation, and a diet poor in methyl donors, combine to cause
      lupus in animal models. Similar changes are found in patients with active lupus,
      indicating a mechanism contributing to lupus flares.

PMID- 29649576
TI  - Epigenetic alterations in primary Sjogren's syndrome - an overview.
AB  - Primary Sjogren's syndrome (pSS) is a chronic autoimmune rheumatic disease
      characterized by inflammation of exocrine glands, mainly salivary and lacrimal
      glands. In addition, pSS may affect multiple other organs resulting in systemic
      manifestations. Although the precise etiology of pSS remains elusive, pSS is
      considered to be a multi-factorial disease, where underlying genetic
      predisposition, environmental factors and epigenetic mechanisms contribute to
      disease development. Epigenetic mechanisms, such as DNA methylation, histone
      modifications and non-coding RNAs, may constitute a dynamic link between genome,
      environment and phenotypic manifestation by their modulating effects on gene
      expression. A growing body of studies reporting altered epigenetic landscapes in
      pSS suggests that epigenetic mechanisms play a role in the pathogenesis of pSS,
      and the reversible nature of epigenetic modifications suggests therapeutic
      strategies targeting epigenetic dysregulation in pSS. This article reviews our
      current understanding of epigenetic mechanisms in pSS and discusses implications
      for novel diagnostic and therapeutic approaches.

PMID- 29649577
TI  - Bioinformatics characterization of a cathepsin B transcript from the giant river
      prawn, Macrobrachium rosenbergii: Homology modeling and expression analysis after
      Aeromonas hydrophila infection.
AB  - Cathepsin B is a lysosomal proteolytic enzyme that has been suggested to play a
      role in pathological processes of immune system. In this study, the full-length
      cDNA sequence of cathepsin B transcript in the giant river prawn Macrobrachium
      rosenbergii (MrCTSB) was obtained from 454 pyrosequencing of cDNAs from
      hepatopancreas and muscle. It was 1158 bp in length, containing an open reading
      frame (ORF) of 987 bp corresponding to 328 amino acids. The predicted molecular
      mass and pI of MrCTSB protein was 36.04 kDa and 4.73. The major characteristics
      of MrCTSB protein consisted of a propeptide of C1 peptidase family at the N
      terminus and a cysteine protease (Pept_C1) domain at the C-terminus. The 3
      dimentional structure of MrCTSB was constructed by computer-assisted homology
      modeling. The folding of MrCTSB was highly conserved to human CTSB structure and
      the modeled MrCTSB displayed characteristics of cysteine proteinases superfamily.
      The docking study was performed to investigate binding interactions between known
      inhibitors against MrCTSB. Known inhibitors were oriented in the groove of
      catalytic site cleft. They bound to subsites from S2, S1, S1', and S2',
      respectively, with key residues in each subsite. Challenge of juvenile prawns
      with Aeromonas hydrophila revealed that the MrCTSB transcript in hepatopancreas
      significantly increased at 60-96 h post injection (hpi). This suggested that
      MrCTSB may play roles in innate immunity of M. rosenbergii. Our results provide
      useful information for a more comprehensive study in immune-related functions of
      MrCTSB.

PMID- 29649578
TI  - Emergence and multiple reassortments of French 2015-2016 highly pathogenic H5
      avian influenza viruses.
AB  - From November 2015 to August 2016, 81 outbreaks of highly pathogenic (HP) H5
      avian influenza virus were detected in poultry farms from South-Western France.
      These viruses were mainly detected in farms raising waterfowl, but also in
      chicken or guinea fowl flocks, and did not induce severe signs in waterfowl
      although they did meet the HP criteria. Three different types of neuraminidases
      (N1, N2 and N9) were associated with the HP H5 gene. Full genomes sequences of 24
      H5HP and 6 LP viruses that circulated in the same period were obtained by next
      generation sequencing, from direct field samples or after virus isolation in SPF
      embryonated eggs. Phylogenetic analyses of the eight viral segments confirmed
      that they were all related to the avian Eurasian lineage. In addition, analyses
      of the "Time of the Most Recent Common Ancestor" showed that the common ancestor
      of the H5HP sequences from South-Western France could date back to early 2014 (+/
      1 year). This pre-dated the first detection of H5 HP in poultry farms and was
      consistent with a silent circulation of these viruses for several months.
      Finally, the phylogenetic study of the different segments showed that several
      phylogenetic groups could be established. Twelve genotypes of H5HP were detected
      implying that at least eleven reassortment events did occur after the H5HP
      cleavage site emerged. This indicates that a large number of co-infections with
      both highly pathogenic H5 and other avian influenza viruses must have occurred, a
      finding that lends further support to prolonged silent circulation.

PMID- 29649581
TI  - A large-scale phylogeny of Microhylidae inferred from a combined dataset of 121
      genes and 427 taxa.
AB  - The phylogenetic relationships of Microhylidae, the third largest family of
      extant frogs, have been difficult to resolve. In the past decade, large amounts
      of sequence data have been deposited for almost every microhylid genus, but no
      study has attempted to combine these data to reconstruct a comprehensive
      phylogeny for this family. In this study, we sequenced 20 near-complete or
      partial microhylid mitochondrial genomes and integrated them with all available
      sequences of Microhylidae from GenBank to construct a supermatrix containing 121
      genes (14 mitochondrial and 107 nuclear protein-coding genes). The combined
      dataset is 112,328 characters long (average sequence data length per species =
      7829 bp), includes 427 microhylid taxa, and covers all but three genera of the
      entire family. This dataset provides strong support for the traditional
      classification of 11 nominal subfamilies and improves the phylogenetic resolution
      of the relationships among subfamilies. The African subfamily Phrynomerinae is
      the sister group of all the other microhylids, and the African subfamily
      Hoplophryninae is the sister taxon to a clade comprising the remaining 9
      subfamilies. At the genus level, our analyses confirm the monophyly of most but
      not all microhylid genera. In summary, we present a new large-scale phylogeny of
      microhylid frogs that should be valuable for addressing their classification and
      for comparative evolutionary studies.

PMID- 29649579
TI  - Prognostic value of nutrition status in the response of cardiac resynchronization
      therapy.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) is indicated in symptomatic
      heart failure (HF) patients after achieving optimal medical therapy. However,
      there are still a large percentage of patients who do not respond to CRT.
      Malnutrition is a frequent comorbidity in patients with HF, and it is associated
      with a poorer prognosis. Here, we evaluate the nutritional status of patients
      assessed by Controlling Nutritional Status (CONUT) score and its association with
      structural remodeling and cardiovascular events. METHODS: We investigated the
      effect of CONUT on HF/death in 302 consecutive patients with a CRT device
      implanted between 2005 and 2015 in a single tertiary center. We categorized the
      patients into three groups: normal nutritional status (CONUT 0-1), mild
      malnutrition (CONUT 2-4) and moderate-severe malnutrition (CONUT >= 5). Changes
      in nutritional status were assessed in patients with mild-to-severe malnutrition
      prior to CRT. RESULTS: One hundred and forty-eight patients exhibited normal
      nutritional status (49.0%), 99 patients exhibited mild malnutrition (32.8%) and
      55 patients exhibited moderate-severe malnutrition (18.2%). CONUT scores of at
      least 2 were associated with higher risk of HF/death compared with CONUT 0-1.
      Significant left ventricular (LV) reverse remodeling was noted in patients with
      better nutritional status. In addition, those malnutrition patients at baseline
      that improved nutritional state exhibited fewer HF/death events at follow-up.
      CONCLUSION: CONUT score prior to CRT was an independent risk factor of death/HF
      and was correlated with LV reverse remodeling. Improvements in CONUT score during
      long-term follow-up were associated with a reduction in the rate of HF/death.

PMID- 29649582
TI  - Adaptation of Mge1 to oxidative stress by local unfolding and altered Interaction
      with mitochondrial Hsp70 and Mxr2.
AB  - Perturbations in mitochondrial redox levels oxidize nucleotide exchanger Mge1,
      compromising its ability to bind to the Hsp70, while the Mxr2 enzyme reduces the
      oxidized Mge1. However, the effects of persistent oxidative stress on Mge1
      structure and function are not known. In this study, we show that oxidation
      induced selective and local structural adaptations cause the detachment of Mge1
      from Hsp70. Notably, persistent oxidative stress causes monomeric Mge1 to
      aggregate and to generate amyloid-type particles. Mxr2 appears to protect Mge1
      from oxidative stress induced aggregation. We conclude that the Mxr2-Mge1-Hsp70
      protein triad is finely regulated through structural alterations of Mge1 mediated
      by redox levels.

PMID- 29649580
TI  - Differential responses of autonomic function in sea level residents, acclimatized
      lowlanders at >3500 m and Himalayan high altitude natives at >3500 m: A cross
      sectional study.
AB  - We studied the differential responses of autonomic function in sea level
      residents (SLR), acclimatized lowlanders (ALH) in high altitude (HA) and HA
      natives (HAN) at >3500 m. Out of 771 male volunteers included in this cross
      sectional study, SLR, ALH and HAN groups were comprised of 351, 307 and 113
      volunteers, respectively. Our results showed persistent sympathetic dominance
      with significantly reduced (p < 0.05) parasympathetic response in ALH as compared
      to SLR and HAN populations. This may be attributed to significantly increased (p
      < 0.05) concentration of coronary risk factors and plasma catecholamines in ALH
      as compared to SLR and HAN. The ALH also showed significantly increased (p <
      0.05) level of serum homocysteine as compared to SLR. The HAN exhibited no
      changes in autonomic function despite significantly elevated (p < 0.05)
      homocysteine level as compared to SLR. Our findings may have clinical relevance
      for assessment of susceptibility to cardiovascular risks in HA dwellers, native
      highlanders and patients with hypoxemia.

PMID- 29649583
TI  - Noradrenergic beta-receptor antagonism in the basolateral amygdala impairs
      reconsolidation, but not extinction, of alcohol self-administration: Intra-BLA
      propranolol impairs reconsolidation of alcohol self-administration.
AB  - A critical barrier to recovery from alcohol addiction is relapse propensity.
      Alcohol cues can trigger relapse, and pharmacologically facilitating processes
      such as extinction, which decreases cue associations, may help prevent relapse.
      The noradrenergic system mediates extinction learning for alcohol; however, the
      neural locus of this effect is unknown. This study sought to determine whether
      the basolateral amygdala (BLA), a region critical for fear extinction, also
      mediates extinction of alcohol seeking. Hooded Wistar rats (N = 12-15 per
      experiment) were implanted with bilateral cannula targeting the BLA and trained
      to lever press for 10% ethanol during auditory or visual cues. Infusions of the
      beta-receptor antagonist propranolol (2 ug/side) were administered prior to
      extinction (Experiment 1), and rats assessed for relapse-like behaviour two weeks
      later, thus allowing for spontaneous recovery. We expected intra-BLA propranolol
      to impair extinction learning; however, propranolol-treated rats exhibited
      reduced responding in the test of spontaneous recovery, suggesting enhanced
      extinction. We investigated this unexpected result by determining if propranolol
      treatment affected memory processes other than extinction. In a subsequent
      experiment, rats were infused with propranolol immediately after extinction to
      target consolidation of extinction (Experiment 2a), and assessed for spontaneous
      recovery. Propranolol was also infused after self-administration to target
      reconsolidation of the original learning (Experiment 2b). Propranolol treatment
      had no effect on consolidation of extinction learning, but impaired
      reconsolidation of self-administration. Propranolol administered prior to a self
      administration session did not affect reinforced responding (Experiment 2c).
      Extinction and reconsolidation are opposing processes triggered by specific test
      conditions. We suggest our test conditions induced reconsolidation of self
      administration memory by propranolol, rather than modulation of extinction. Thus,
      our data implicates intra-BLA noradrenergic beta-receptors in reconsolidation of
      alcohol self-administration memory.

PMID- 29649584
TI  - Molecular cloning, expression and biochemical characterization of hemoglobin gene
      from ark shell Scapharca broughtonii.
AB  - Hemoglobin, the main component of haemolymph, is widely distributed in animals.
      Although its important oxygen transport functions has been extensively reported,
      studies on the immune function of hemoglobin in mollusc are few. Research on
      immune of hemoglobin of ark shell Scapharca broughtonii attracted more and more
      attention due to its ownership of erythrocyte comparing with many other
      shellfish. In this study, the hemoglobin cDNA of S. broughtonii was cloned by EST
      and RACE methods (named as SbHb). Sequence analysis revealed that the cDNA was
      946 bp in length, including an open reading frame (ORF) of 459 bp which encoded a
      polypeptide of 152 amino acid residues, and a 5'-untranslated region (UTR) of 313
      bp, a 3'-UTR of 174 bp. Sequence and homology analysis showed that the SbHb
      shared similarity with that of other related species. The mRNA expression
      profiles of SbHb in tested tissues analyzed by quantitative real-time PCR (qRT
      PCR) revealed that the mRNA of SbHb could be all detected in foot, gill, mantle,
      adductor muscle, haemocytes and hepatopancreas, and the highest level was found
      in the haemocytes, which is 163.2 times higher than that in adductor muscle.
      Vibrio anguillarum stimulation and hypoxia treatment both had significant impact
      on the expression of SbHb, which showed the same trends as increasing first to
      the highest at 16 h after treatment and then followed by declining. Recombinant
      protein of SbHb (rSbHb) was successfully obtained by prokaryotic expression, and
      further function analysis indicated obviously that the rSbHb had very strong
      phenoloxidase-like activity (PO-like activity) and it could remarkably inhibit
      growth of gram-negative bacteria V. anguillarum. All the data suggested that the
      SbHb plays a significant role in the process of antibacterial and anoxia
      tolerance reaction in S. broughtonii, providing the evidence that SbHb is a key
      immune factor.

PMID- 29649585
TI  - Effects of different serotonin receptor subtype antagonists on the development of
      cardiac allograft vasculopathy in murine aortic allografts.
AB  - BACKGROUND: Cardiac allograft vasculopathy (CAV) is the main obstacle for long
      term survival after heart transplantation. Alloimmune mediated chronic vascular
      rejection results in several mechanisms like platelet activation, immigration of
      inflammatory cells through the endothelial layer and proliferation and migration
      of smooth muscle cells (SMCs). Serotonin (5-HT) promotes these processes via
      activation of 5-HT2 receptors. We hypothesized that inhibiting 5-HT2 receptors
      ameliorates the development of CAV. METHODS: CBA/JRj mice recieved aortic grafts
      from C57BL/6 mice. After transplantation until recovery of organs, recipients
      were treated with serotonin receptor antagonists: sarpogrelate (5-HT2A), SB
      204741 (5-HT2B) or terguride (5-HT2A+B). Mice were sacrificed after 14 days for
      qRT-PCR analysis or after 30 days for histological evaluation. Serum serotonin
      ELISA was done at both time points. RESULTS: Elevated serum serotonin levels were
      significantly reduced after 5-HT2A antagonist treatment as was 5-HT2A receptor
      expression. This went along with reduced inflammation characterized by
      significantly fewer infiltrating macrophages and pro-inflammatory intragraft
      cytokines and with reduced tissue remodeling evident as significantly less
      neointima formation. CONCLUSION: Inhibition of the 5HT/5-HT2A receptor axis leads
      to significantly reduced neointima proliferation after aortic transplantation
      associated with reduced transendothelial migration of macrophages and decreased
      expression of inflammatory cytokines. These findings have translational
      implications as inhibitors of 5HT2A like sarpogrelate are already approved for
      clinical use.

PMID- 29649586
TI  - Nephrotoxicity of piperacillin/tazobactam combined with vancomycin: should it be
      a concern?
AB  - The combination of piperacillin/tazobactam (TZP) and vancomycin (VAN) provides a
      wide spectrum of activity against many pathogens acquired in healthcare settings.
      However, there have been reports of increased potential for nephrotoxicity with
      this combination. The aim of this study was to evaluate the nephrotoxic effect of
      TZP+VAN and to compare it with that of TZP and VAN monotherapies as well as VAN +
      meropenem (MEM), another broad-spectrum combination. A total of 402 patients
      receiving any of the antimicrobial regimens for >48 h were evaluated
      retrospectively over a 2-year period (2012-2013). Patients admitted to the
      intensive care unit, those with a baseline serum creatinine >2.0 mg/dL, patients
      on haemodialysis or peritoneal dialysis, pregnant women and those in septic shock
      were excluded. The presence and severity of acute kidney injury (AKI) was
      assessed according to the AKIN criteria. The incidence of AKI was significantly
      higher in the TZP+VAN group (41.3%) compared with the TZP (16.0%), VAN (15.7%)
      and VAN+MEM (10.1%) groups (P < 0.001). In the multivariate analysis, the risk of
      AKI increased 3.5-fold in patients treated with TZP+VAN and 1.7-fold in those who
      were receiving a potentially nephrotoxic drug when the antibiotic regimen was
      started compared with patients treated with VAN alone. Combined use of TZP+VAN
      carries a much higher risk of AKI than either antibiotic monotherapy regimen.
      Therefore, this broad-spectrum combination should be used cautiously in patients
      with a high likelihood of developing kidney injury.

PMID- 29649587
TI  - A novel tool against multiresistant bacterial pathogens: lipopeptide modification
      of the natural antimicrobial peptide ranalexin for enhanced antimicrobial
      activity and improved pharmacokinetics.
AB  - As evolutionarily optimised defence compounds, antimicrobial peptides (AMPs)
      represent a powerful tool against bacterial infections. Ranalexin, an AMP found
      in the skin of the American bullfrog (Rana catesbeiana), is primarily active
      against Gram-positive bacteria, with minimum inhibitory concentrations (MICs) of
      8-16 mg/L, but shows weaker activity against Gram-negative bacteria (MICs > 64
      mg/L). By substitution of six N-terminal amino acids by saturated fatty acids
      [decanoic acid (C10:0) to myristic acid (C14:0)], lipopeptide derivatives with
      enhanced antimicrobial activity were developed. The antimicrobial capacity of the
      peptides was tested against different bacterial strains, including multiresistant
      clinical isolates. C13C3lexin, the most potent derivative, showed MICs of 2-8
      mg/L against Gram-positive bacteria and 2-16 mg/L against Gram-negative bacteria.
      In time-kill studies, it was clearly shown that ranalexin and the lipopeptide
      C13C3lexin function as concentration-dependent, fast-acting substances against
      different bacteria. Cell viability assays revealed that cytotoxicity towards
      human cells increases with the chain length of the attached fatty acid (IC50,
      12.74-108.10 ug/mL). Furthermore, using positron emission tomography (PET)
      imaging, pharmacokinetic studies of 68Ga-labelled ranalexin and its derivatives
      were performed for the first time. Here it was demonstrated that ranalexin is
      rapidly cleared via the kidneys within 1 h post-injection. In contrast, the
      lipopeptide showed greatly extended circulation in the bloodstream and a shift
      from renal to hepatic accumulation characteristics. Therefore, the more
      favourable pharmacokinetics and enhanced antimicrobial activity clearly
      demonstrate the potential of the lipopeptide AMPs as novel ammunition against
      emerging multiresistant bacterial pathogens.

PMID- 29649588
TI  - Characterisation of OXA-258 enzymes and AxyABM efflux pump in Achromobacter
      ruhlandii.
AB  - OBJECTIVES: The aim of this study was to characterise OXA-258 variants and other
      features that may contribute to carbapenem resistance in Achromobacter ruhlandii.
      METHODS: Kinetic parameters for purified OXA-258a and OXA-258b were determined
      measuring the rate of hydrolysis of a representative group of antimicrobial
      agents. Whole-genome shotgun sequencing was performed on A. ruhlandii 38
      (producing OXA-258a) and A. ruhlandii 319 (producing OXA-258b), and in silico
      analysis of antimicrobial resistance determinants was conducted. Substrates of
      the AxyABM efflux pump were investigated by inhibition assays using phenylalanine
      arginine beta-naphthylamide (PAbetaN). Outer membrane protein profiles were
      resolved by 12% sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS
      PAGE). RESULTS: Kinetic measurements of purified OXA-258 variants displayed an
      overall weak catalytic efficiency toward beta-lactams. A detectable hydrolysis of
      imipenem was observed. In silico genomic analysis confirmed the presence of 32
      and 35 putative efflux pump-encoding genes in A. ruhlandii strains 38 and 319,
      respectively. Complete sequences for AxyABM and AxyXY efflux pumps, previously
      described in Achromobacter xylosoxidans, were detected. Decreases in the MICs for
      chloramphenicol, nalidixic acid and trimethoprim/sulfamethoxazole were observed
      in the presence of the inhibitor PAbetaN, suggesting that these antibiotics are
      substrates of AxyABM. AxyXY-encoding genes of A. ruhlandii 38 and A. ruhlandii
      319 displayed 99% identity. No differences were observed in the outer membrane
      protein profiles. CONCLUSIONS: The contribution of OXA-258 enzymes to the final
      beta-lactam resistance profile may be secondary. Further studies on other
      putative resistance markers identified in the whole-genome analysis should be
      conducted to understand the carbapenem resistance observed in A. ruhlandii.

PMID- 29649589
TI  - Production of trans-chrysanthemic acid, the monoterpene acid moiety of natural
      pyrethrin insecticides, in tomato fruit.
AB  - The pyrethrum plant, Tanacetum cinerariifolium (Asteraceae) synthesizes a class
      of compounds called pyrethrins that have strong insecticidal properties but are
      safe to humans. Class I pyrethrins are esters of the monoterpenoid trans
      chrysanthemic acid with one of three jasmonic-acid derived alcohols. We
      reconstructed the trans-chrysanthemic acid biosynthetic pathway in tomato fruits,
      which naturally produce high levels of the tetraterpene pigment lycopene, an
      isoprenoid which shares a common precursor, dimethylallyl diphosphate (DMAPP),
      with trans-chrysanthemic acid. trans-Chrysanthemic acid biosynthesis in tomato
      fruit was achieved by expressing the chrysanthemyl diphosphate synthase gene from
      T. cinerariifolium, encoding the enzyme that uses DMAPP to make trans
      chrysanthemol, under the control of the fruit specific promoter PG, as well as an
      alcohol dehydrogenease (ADH) gene and aldehyde dehydrogenase (ALDH) gene from a
      wild tomato species, also under the control of the PG promoter. Tomato fruits
      expressing all three genes had a concentration of trans-chrysanthemic acid that
      was about 1.7-fold higher (by weight) than the levels of lycopene present in non
      transgenic fruit, while the level of lycopene in the transgenic plants was
      reduced by 68%. Ninety seven percent of the diverted DMAPP was converted to trans
      chrysanthemic acid, but 62% of this acid was further glycosylated. We conclude
      that the tomato fruit is an alternative platform for the biosynthesis of trans
      chrysanthemic acid by metabolic engineering.

PMID- 29649590
TI  - Effective intracellular delivery and Th1 immune response induced by ovalbumin
      loaded in pH-responsive polyphosphazene polymersomes.
AB  - A polymersome system for delivering protein antigen ovalbumin (OVA) based on
      amphiphilic polyphosphazene grafting with N,N-diisopropylethylenediamine (DPA)
      and poly(ethylene glycol) (PEG) groups (poly[(DPA)m (PEG)n phosphazene], PEDP)
      was designed and constructed. The 200-240 nm-size OVA-loaded polymersomes
      displayed high stability at physiological pH, slow internalization through
      clathrin-mediated endocytosis pathway, and then a pH-triggered sustained OVA
      release in acidic environment, leading to extensive antigen access to cytosol.
      Prime-boost vaccine kept high antibody titers for 8 weeks and the subcutaneous
      vaccine of OVA polymersomes biased the immune response towards a type 1 T helper
      (Th1) response. Animal experiment results showed that the antigen-specific
      prophylactic vaccination by PEDP polymersomes delivery was much more rapid and
      efficient in depressing tumor growth and progress when compared with the
      therapeutic vaccination. These results suggested that PEDP-based polymersomes are
      very promising in controlled cytosolic delivery of protein antigens, and enhanced
      Th1 specific immune response.

PMID- 29649591
TI  - Inhalable gadofullerenol/[70] fullerenol as high-efficiency ROS scavengers for
      pulmonary fibrosis therapy.
AB  - Pulmonary fibrosis has become a fatal disease for its high incidence and few
      effective drugs available in clinic. In this study, gadofullerenol (GF-OH) and
      [70] fullerenol (C70-OH) nanoparticles (NPs) prepared by a one-pot reaction were
      designed as nanomedicines to treat this fatal disease. It was revealed that the
      inhalation of gadofullerenols and [70] fullerenols substantially alleviates the
      collagen deposition induced by acute lung injury. Based on detailed studies of
      oxidative stress parameters and transforming growth factor-beta1 (TGF-beta1), we
      demonstrated they owned the antioxidant and anti-inflammatory functions for the
      modulation of ROS-mediated inflammation process. Thus the therapeutic effect may
      be associated with synergistic mechanism of scavenging free radicals and
      indirectly modulating TGF-beta1 expression. Moreover, GF-OH NPs were observed to
      show the superiority to C70-OH NPs both in vitro and in vivo due to the
      structural distinction. These results suggest the inhalable fullerenols are
      highly potential for clinical therapy of pulmonary fibrosis.

PMID- 29649592
TI  - Development of hybrid scaffold with biomimetic 3D architecture for bone
      regeneration.
AB  - In the present study, a biomimetic three-dimensional hybrid scaffold has been
      designed considering the bone natural architecture with favorable interconnected
      porous structure, nano-microscale features and mechanical strength. The chief
      components of the hybrid scaffold are core-sheath nanofibers and hydrogel,
      suitably arranged to create a bone like microenvironment. Specifically, the core
      sheath nanofibers were coiled tightly into a ring to mimic the osteon, and
      reinforced in a hydrogel matrix. Morphological analysis using SEM and 4D-X-ray
      microscopy revealed that the hybrid scaffold consists of coiled rings of
      nanofibers in highly porous hydrogel matrix showing structural similarity to
      osteons. The reinforcement of electrospun nanofibers in hydrogel influenced the
      mechanical properties of scaffold. The potential application of the biomimetic
      hybrid scaffold, and the role of its specific architecture, was subsequently
      investigated in vitro using a human osteosarcoma fibroblast cell line.
      Furthermore, DNA quantification, alkaline-phosphatase and alizarin assay
      validated the potential of fabricated scaffold for bone tissue-regeneration.

PMID- 29649593
TI  - Gold nanoparticles conjugating recombinant influenza hemagglutinin trimers and
      flagellin enhanced mucosal cellular immunity.
AB  - The immunogenicity of subunit vaccines can be augmented by formulating them into
      nanoparticles. We conjugated recombinant trimetric influenza A/Aichi/2/68(H3N2)
      hemagglutinin (HA) onto functionalized gold nanoparticle (AuNP) surfaces in a
      repetitive, oriented configuration. To further improve the immunogenicity, we
      generated Toll-like receptor 5 (TLR5) agonist flagellin (FliC)-coupled AuNPs as
      particulate adjuvants. Intranasal immunizations with an AuNP-HA and AuNP-FliC
      particle mixture elicited strong mucosal and systemic immune responses that
      protected hosts against lethal influenza challenges. Compared with the AuNP-HA
      alone group, the addition of AuNP-FliC improved mucosal B cell responses as
      characterized by elevated influenza specific IgA and IgG levels in nasal,
      tracheal, and lung washes. AuNP-HA/AuNP-FliC also stimulated antigen-specific
      interferon-gamma (IFN-gamma)-secreting CD4+ cell proliferation and induced strong
      effector CD8+ T cell activation. Our results indicate that intranasal co-delivery
      of antigen and adjuvant-displaying AuNPs enhanced vaccine efficacy by inducing
      potent cellular immune responses.

PMID- 29649594
TI  - Detection of human parvovirus B19 infection in the thymus of patients with thymic
      hyperplasia-associated myasthenia gravis.
AB  - OBJECTIVE: To investigate the association between myasthenia gravis (MG) and
      human parvovirus B19 (B19V) infection in the thymus. METHODS: The presence of
      human B19V DNA and protein was assessed in 138 samples-including 68 thymic
      hyperplasias (39 with MG), 58 thymomas (23 with MG), and 12 normal thymus tissues
      using a nested polymerase chain reaction, immunohistochemistry, laser capture
      microdissection, and sequencing in a double-blinded manner. RESULTS: B19V DNA was
      detected mainly in thymic hyperplasia, and the positivity rate (41.18%, 28/68)
      was significantly higher than that in thymoma (3.45%, 2/58) (p <0.001) but not
      that in normal thymic tissues. Correspondingly, the positivity rate in thymic
      hyperplasia with MG (30.77%, 12/39) was significantly higher than that in thymoma
      with MG (4.35%, 1/23) (p=0.021). However, it was higher in thymic hyperplasia
      without MG (55.17%, 16/29) than in thymic hyperplasia with MG (30.77%, 12/39)
      (p=0.043). Cells in thymic hyperplasia positive for B19V VP1/VP2 protein (63.24%,
      43/68) were identified mainly in ectopic germinal centres and thymic corpuscle
      epithelial cells, but were rare in thymomas (1.72%, 1/58) (p <0.001). Moreover,
      the positivity rate was significantly higher in thymic hyperplasia with MG
      (74.36%, 29/39) than in thymic hyperplasia without MG (48.28%, 14/29) (p=0.027).
      CONCLUSIONS: To our knowledge, the present study is the first to show that human
      B19V infection is closely associated with thymic hyperplasia and thymic
      hyperplasia-associated MG, but is not related to thymoma or thymoma-associated
      MG. The findings reveal a previously unrecognized aetiopathogenic mechanism of
      thymic-hyperplasia-associated MG, evoking numerous questions that require further
      investigation.

PMID- 29649595
TI  - The paradox of vaccine hesitancy among healthcare professionals.

PMID- 29649596
TI  - Population pharmacokinetics and pharmacodynamics of fosfomycin in non-critically
      ill patients with bacteremic urinary infection caused by multidrug-resistant
      Escherichia coli.
AB  - OBJECTIVES: To describe the population pharmacokinetics of fosfomycin for
      patients with bacteraemic urinary tract infection (BUTI). The analysis identified
      optimal regimens on the basis of pharmacodynamic targets and assessed the
      adequacy of Clinical and Laboratory Standards Institute (CLSI) and European
      Committee on Antimicrobial Susceptibility Testing (EUCAST) susceptibility
      breakpoints for Escherichia coli. METHODS: Data of 16 patients with BUTI caused
      by multidrug-resistant E. coli (FOREST clinical trial) received intravenous
      fosfomycin (4 g every 6 hours) were analysed. A population pharmacokinetic
      analysis was performed, and Monte Carlo simulations were undertaken using 4 g
      every 6 hours and 8 g every 8 hours. The probability of pharmacodynamic target
      attainment was assessed using pharmacodynamic targets for E. coli for static
      effect, 1-log drop in bacterial burden and resistance suppression. RESULTS: Sixty
      four plasma samples were collected over a single dosing interval (day 2 or 3
      after starting fosfomycin treatment). Fosfomycin concentrations were highly
      variable. Pharmacodynamic target attainment analysis showed mild improvement by
      increasing fosfomycin dosing (4 g every 6 hours vs. every 8 hours). These dosages
      showed success for decreasing 1-log bacterial burden in 89% to 96% (EUCAST
      breakpoints) and 33% to 54% (CLSI breakpoints) of patients, but they were unable
      to reach bacterial resistance suppression targets. CONCLUSIONS: Fosfomycin
      concentrations are highly variable-a fact partially explained by renal
      impairment. The present work supports the use of 4 g every 6 hours as an
      effective regimen for the treatment of non-critically ill patients with BUTI
      caused by multidrug-resistant E. coli, as higher dosages might increase toxicity
      but may not significantly increase efficacy. The current information may suggest
      that fosfomycin susceptibility breakpoints need to be reappraised.

PMID- 29649597
TI  - The temptation of large numbers.

PMID- 29649598
TI  - Methicillin resistance in Staphylococcus aureus infections among patients
      colonized with methicillin-susceptible Staphylococcus aureus.
AB  - OBJECTIVES: We have noticed that patients colonized with methicillin-susceptible
      Staphylococcus aureus (MSSA) rarely get methicillin-resistant S. aureus (MRSA)
      infections. The purpose of this study was to compare the odds of a Staphylococcus
      aureus (SA) infection being an MRSA infection in MSSA carriers, MRSA carriers and
      non-carriers of SA. METHODS: Hospitalizations of adult patients at the Cleveland
      Clinic Health System from 2008 to 2015 were screened to identify those where the
      patient was tested for SA colonization. The first such hospitalization was
      identified. Among these 90 891 patients, those who had an SA infection during the
      hospitalization were included. SA carrier status (MRSA, MSSA, or non-carrier),
      was defined based on the first nasal SA test result. The association of carrier
      status and MRSA infection was examined. RESULTS: The mean (+/-standard deviation
      (SD)) age of the 1999 included patients was 61 (17) years, and 1160 (58%) were
      male. Thirty percent, 26%, and 44%, were MRSA carriers, MSSA carriers and non
      carriers, respectively. Of the 601 SA infections in MRSA carriers (reference
      group), 552 (92%) were MRSA infections compared with 42 (8%) of 516 in MSSA
      carriers (odds ratio (OR) 0.008, 95% confidence interval (CI) 0.005-0.012, p
      <0.0001) and 430 (49%) of 882 in non-carriers (OR 0.072, 95% CI 0.051-0.100, p
      <0.0001), after controlling for age, sex, hospital length of stay and calendar
      year. CONCLUSION: Among patients with SA infection, the odds of the infection
      being an MRSA infection are 125-times lower in an MSSA carrier than in an MRSA
      carrier.

PMID- 29649599
TI  - Time-dependent differences in management and microbiology of orthopaedic internal
      fixation-associated infections: an observational prospective study with 229
      patients.
AB  - OBJECTIVES: Little information has been published on orthopaedic internal
      fixation-associated infections. We aimed to analyse time-dependent microbiology,
      treatment, and outcome. METHODS: Over a 10-year period, all consecutive patients
      with internal fixation-associated infections at the University Hospital of Basel,
      were prospectively followed and clinical, microbiological and outcome data were
      acquired. Infections were classified as early (0-2 weeks after implantation),
      delayed (3-10 weeks), and late (>10 weeks). RESULTS: Two hundred and twenty-nine
      patients were included, with a median follow-up of 773 days (IQR 334-1400).
      Staphylococcus aureus was the most prevalent pathogen (in 96/229 patients,
      41.9%). Enterobacteriaceae were frequent in early infections (13/49, 26.5%),
      whereas coagulase-negative staphylococci (36/92, 39.1%), anaerobes (15/92, 16.3%)
      and streptococci (10/92, 10.9%) increased in late revisions. Failure was observed
      in 27/229 (11.7%). Implants were retained in 42/49 (85.7%) in early, in 51/88
      (57.9%) in delayed, and in 9/92 (9.8%) in late revisions (p < 0.01). Early
      revisions failed in 6/49 (12.2%), delayed in 9/88 (10.2%), and late in 11/92
      (13.0%) (p 0.81). Debridement and retention failed in 6/42 (14.3%) for early, in
      6/51 (11.8%) for delayed, and in 3/9 (33.3%) for late revisions (p 0.21). Biofilm
      active antibiotic therapy tailored to resistance correlated with improved outcome
      for late revisions failure (6/72, 7.7% versus 6/12, 50.0%; p < 0.01) but not for
      early revisions failure (5/38, 13.2% versus 1/11, 9.1%; p 1.0). CONCLUSIONS:
      Treatment of internal fixation-associated infections showed a high success rate
      of 87-90% over all time periods. Implant retention was highly successful in early
      and delayed infections but only limited in late infections.

PMID- 29649600
TI  - Siderophore-antibiotic conjugates: exploiting iron uptake to deliver drugs into
      bacteria.

PMID- 29649601
TI  - Adjuvant non-bacteriolytic and anti-inflammatory combination therapy in
      pneumococcal meningitis: an investigation in a mouse model.
AB  - OBJECTIVES: Therapy with antibiotics, dexamethasone, and supportive intensive
      care has improved the prognosis of pneumococcal meningitis, but mortality remains
      high. Here, we investigated an adjunctive combination therapy of the non
      bacteriolytic antibiotic daptomycin plus several anti-inflammatory agents to
      identify the currently most promising adjunctive combination therapy for
      pneumococcal meningitis. METHODS: C57BL/6 mice were infected by injection of
      pneumococci into the cisterna magna. Treatment was begun 21 h after infection,
      and consisted of ceftriaxone plus (a) dexamethasone, (b) dexamethasone plus
      daptomycin, (c) daptomycin, (d) daptomycin plus an anti-IL1 antibody, (e)
      daptomycin plus roscovitine, or (f) daptomycin plus an anti-C5 antibody. Animals
      were followed until 45 h after infection. Furthermore, adjunctive daptomycin plus
      anti-C5 antibodies were assessed in a long-term follow-up. RESULTS: Adjunctive
      treatment with daptomycin and an anti-C5 antibody was superior to adjunctive
      dexamethasone and reduced disease symptoms (clinical score 1.1 +/- 1.1 versus 5.0
      +/- 2.7, p < 0.0083), improved explorative activity (open field test 17.8 +/- 8.2
      versus 7.4 +/- 4.3 crossed fields/2 minutes, p < 0.0083), and reduced hearing
      impairment (thresholds for click stimulus 96.1 +/- 14.7 versus 114.8 +/- 9.3 dB
      SPL, p < 0.0083) in the acute stage. Furthermore, explorative activity (14.4 +/-
      7.3 crossed fields/2 minutes versus 6.3 +/- 7.2, p < 0.05) and cognitive function
      (t-maze test, exploration time previously unknown alley 72.4 +/- 14.3 versus 48.7
      +/- 25.6%, p < 0.05) was improved at 2 weeks after infection. Treatment with
      daptomycin plus an anti-IL-1beta antibody or roscovitine was not of significant
      benefit in comparison to adjunctive therapy with dexamethasone. CONCLUSIONS: An
      adjunctive combination of the non-lytic antibiotic daptomycin plus an anti-C5
      antibody was superior to standard therapy with adjunctive dexamethasone in the
      treatment of pneumococcal meningitis.

PMID- 29649602
TI  - Point-of-care and point-of-'can': leveraging reference-laboratory capacity for
      integrated diagnosis of fever syndromes in the tropics.
AB  - BACKGROUND: There is an urgent need for integrated diagnosis of febrile syndromes
      able to account for multiple pathogens and to inform decisions for clinical care
      and public health. AIMS: To reflect on the evolving roles of laboratory-based
      testing for non-malarial febrile illnesses (NMFIs) in low-resource settings, and
      to consider how advances in diagnostics, in connectivity and transport, and in
      implementation of quality systems may substantially enhance the capacity of
      reference laboratories to bridge the current gap between remote passive
      surveillance and clinically meaningful integrated fever diagnosis. SOURCES:
      Iterative search of PubMed databases, organizational reports, and expert
      consultation. CONTENT: Implementation of new technologies-such as very broad
      molecular panels for surveillance and mass spectrometry-may considerably diminish
      capability gaps in reference laboratories in low-resource settings. Although the
      need for clinical bacteriology diagnostics is now recognized, the lack of new
      simple and rapid phenotypic tests for antimicrobial resistance remains a key
      deficiency. Several initiatives to strengthen diagnostic preparedness for
      infectious disease outbreaks have highlighted the need for functional tiered
      laboratory networks. Recently, dramatic headway in connectivity-such as combining
      automated readers with the image processing and data transmission capabilities of
      smartphones-now allows for more complex testing and interfacing with distant
      laboratory information systems while reducing workload and errors. Together with
      connectivity to transmit and receive results, new approaches to specimen
      collection and transport-such as the validation of rectal swabs and the use of
      aerial drones to transport specimens to distant laboratories-now make remote
      testing feasible. The above innovations also open up the possibility of
      implementing quality systems through community-level diagnostic stewardship.
      Finally, strengthened laboratory networks actively support the feasibility of
      implementing quality-assured point-of-care testing where it is needed.
      IMPLICATIONS: Recent advances offer the present-day possibility of innovations to
      re-invent the relationship between distant reference laboratories and end-users
      for integrated diagnosis of NMFIs.

PMID- 29649603
TI  - Rotavirus vaccine effectiveness in preventing hospitalizations due to
      gastroenteritis: a descriptive epidemiological study from Germany.
AB  - OBJECTIVES: Rotavirus infections are common causes of infant hospitalization. The
      present study examined the effectiveness of anti-rotavirus vaccination in
      preventing rotavirus-related hospitalizations in Germany, following its state and
      nationwide introductions in 2008 and 2013, respectively. METHODS: During 15
      consecutive seasons 9557 stool samples of hospitalized children of 5 years and
      younger with acute gastroenteritis were screened for rotavirus A. Rotavirus G and
      P genotypes were assessed after vaccine introduction. Vaccine effectiveness was
      determined by comparison of rotavirus incidence in pre-vaccine and post-vaccine
      cohorts. The herd effect was calculated as the difference between the observed
      reduction of rotavirus-related hospitalizations and the expected direct vaccine
      effect. RESULTS: The number of rotavirus-related hospitalizations declined after
      vaccine introduction. Approximately 26% (503/1955) of prevented cases could be
      attributed to the herd effect. Human rotaviruses of genotypes G3P[8], G1P[8],
      G9P[8], G4P[8], G2P[4] and G12P[8] were most frequent. Uncommon genotypes
      remained rare. The direct, indirect, total and overall vaccine effectiveness was
      86% (95% confidence interval (CI) 83.2-89.1%), 48% (95% CI 42.8-52.6%), 93% (95%
      CI 91.3-94.3%) and 69% (95% CI 66.5-72.0%), respectively. There was no
      significant difference in vaccine-type or in genotype-specific vaccine
      effectiveness. CONCLUSIONS: Anti-rotavirus vaccination efficiently reduced
      rotavirus-related hospitalizations in Germany in the past decade. The vaccines
      analysed in this article provide a broadly heterologous and long-lasting
      protection. The herd effect substantially contributed to the observed drop in the
      number of incidences of severe rotavirus infections. Presumably, constant high
      vaccine coverage will lead to a continued upward trend in the overall vaccine
      efficiency.

PMID- 29649604
TI  - Clonorchis sinensis omega-class glutathione transferases are reliable biomarkers
      for serodiagnosis of clonorchiasis and opisthorchiasis.
AB  - OBJECTIVES: To determine the potential for immunodiagnostic application of two
      recombinant forms of Clonorchis sinensis omega-class glutathione transferases
      (rCsGSTo1 and rCsGSTo2) against human small liver-fluke C. sinensis and
      Opisthorchis viverrini infections. METHODS: Specific antibody levels against
      rCsGSTo1 and rCsGSTo2 in patients' sera of egg-positive opisthorchiasis (n = 87)
      and clonorchiasis (n = 120), as well as those in sera from patients with other
      helminthic infections (n = 252) and healthy controls (n = 40) were
      retrospectively analysed by ELISA. RESULTS: We observed highly positive
      correlation coefficients between specific antibody levels against rCsGSTo1 and
      rCsGSTo2 and egg counts per gramme of faeces (EPG) of patients with
      opisthorchiasis (n = 87; r = 0.88 for rCsGSTo1 and r = 0.90 for rCsGSTo2). Sera
      from opisthorchiasis patients whose EPG counts >100 (n = 43) revealed high
      antibody titres against both antigens. Patients' sera with low EPG counts (<100,
      n = 44) also exhibited reliable sensitivities of 93.2% and 97.7% for rCsGSTo1 and
      rCsGSTo2, respectively. Sera from clonorchiasis patients showed sensitivities of
      90% (108/120 samples) and 89.2% (107/120 sera) for rCsGSTo1 and rCsGSTo2. Overall
      diagnostic sensitivities for liver-fluke infections were 92.3% for rCsGSTo1
      (191/207 samples) and 93.2% for rCsGSTo2 (193/207 samples). Specificities were
      89.7% (rCsGSTo1) and 97.6% (rCsGSTo2). CONCLUSIONS: Detection of specific
      antibody levels against rCsGSTo1 or rCsGSTo2 might be promising for the
      serodiagnosis of patients infected with these two phylogenetically close
      carcinogenic liver-flukes.

PMID- 29649605
TI  - Fluoroquinolones for urinary tract infection and within-household spread of
      resistant Enterobacteriaceae: the smoking gun.

PMID- 29649606
TI  - Pharmacokinetics/pharmacodynamics characterization of combined antimicrobial
      agents: a real challenge and an urgent need.

PMID- 29649607
TI  - Hungry neutrophils.

PMID- 29649608
TI  - Stand-alone craniocervical decompression is feasible in children with
      mucopolysaccharidosis type I, IVA, and VI.
AB  - BACKGROUND CONTEXT: In patients with mucopolysaccharidosis (MPS),
      glycosaminoglycan deposits in the dura mater and supporting ligaments cause
      spinal cord compression and consecutive myelopathy, predominantly at the
      craniocervical junction. Disease characteristics of craniocervical stenosis (CCS)
      in patients with MPS differ profoundly from other hereditary and degenerative
      forms. Because of high periprocedural morbidity and mortality, patients with MPS
      pose a substantial challenge to the inexperienced medical care provider. As
      literature remains scarce, we present our experience with a large cohort of
      patients with MPS treated for CCS without atlanto-occipital instrumentation.
      PURPOSE: The present study aimed to describe a safe and least traumatic approach
      for treating CCS in children with MPS, avoiding primary instrumentation. STUDY
      DESIGN: This is a prospective follow-up (cohort) study. PATIENT SAMPLES: We
      report 15 consecutive patients with CCS related to MPS, who were treated with
      stand-alone cervical decompression. OUTCOME MEASURES: Myelopathy was assessed
      using magnetic resonance imaging (MRI), somatosensory evoked potentials, and
      clinical evaluation. Cervical instability was evaluated using plain x-ray and
      MRI. The disability status is quantified using either the Karnofsky or Lansky
      Performance Score. METHODS: We describe 15 consecutive patients treated with
      craniocervical decompression. Data were collected prospectively. The mean follow
      up is 6 years (5 standard deviation). The technique and treatment principles are
      described. RESULTS: The overall clinical outcome in this patient cohort is good
      (mean Karnofsky Performance Score of 80). No patient developed signs of C0-C1-C2
      instability or progressive myelopathy. Restenosis occurred in seven patients,
      requiring a total of eight reoperations. CONCLUSIONS: Surgery in patients with
      MPS is associated with high morbidity and mortality of up to 4.2%. Because of the
      unique nature of the disease, recurring stenosis is inevitable. To shorten the
      procedure time and simplify the anticipated reoperation, we provide data that
      craniocervical decompression is feasible without the necessity of primary
      osteosynthesis. In the absence of craniocervical instability, decompression
      surgery without occipitocervical stabilization yields good postoperative results
      and challenges the long-standing paradigm of prophylactic craniocervical
      fixation.

PMID- 29649609
TI  - Surgical treatment improves survival of elderly with axis fracture-a national
      population-based multiregistry cohort study.
AB  - BACKGROUND CONTEXT: Fractures of the axis (C2) are the most common cervical
      spinal injuries in the elderly population. Several authors have reported improved
      survival among elderly patients with C2 fractures when treated surgically.
      PURPOSE: We aimed to analyze whether surgery improves survival of elderly with C2
      fractures. STUDY DESIGN/SETTING: An observational population-based longitudinal
      multi-registry study was carried out. PATIENT SAMPLE: Swedish Patient Registry
      1997 to 2014 and Swedish Cause of Death Registry 1997 to 2014 served as source of
      patient sample. OUTCOME MEASURES: Survival after C2 fracture according to non
      surgical and surgical treatment was the outcome measure. METHODS: We included all
      patients treated for the primary diagnosis of C2 fracture (10th revision of the
      International Statistical Classification of Diseases and Related Health Problems
      or ICD-10: S12.1) at an age >=70 years and receiving treatment at a health-care
      facility. Non-surgical treatment comprises cervical collar or halo-vest
      treatment. Surgical treatment was identified in the Swedish patient registry
      extract using the Swedish classification of procedural codes. Survival was
      determined using the Kaplan-Meier method. Comorbidity was determined using the
      Charlson Comorbidity Index. RESULTS: Of the included 3,375 elderly patients with
      C2 fractures (43% men, aged 83+/-7 years), 22% were treated surgically. Surgical
      treatment was assigned based on age, gender, and year of treatment. The 1-year
      survival of 2,618 non-surgically treated patients was 72% (n=1,856), and 81%
      (n=614) for the 757 surgically treated (p<.001, relative risk reduction=11%).
      Adjusted for age, gender, comorbidity, and year of injury, surgically treated
      patients had greater survival than non-surgically treated patients (hazard
      ratio=0.88, 95% confidence interval: 0.79-0.97). Among those above 88 years of
      age (95% confidence interval: 85-92), surgical treatment lost its effect on
      survival. CONCLUSIONS: Despite the frailty of elderly patients, the morbidity of
      cervical external immobilization with a rigid collar seemingly weighs greater
      than surgical morbidity, even in octogenarians. For those above 88 years of age,
      non-surgical treatment should be primarily attempted.

PMID- 29649610
TI  - Evaluating the effect of growing patient numbers and changing data elements in
      the National Surgical Quality Improvement Program (NSQIP) database over the
      years: a study of posterior lumbar fusion outcomes.
AB  - BACKGROUND CONTEXT: The use of national databases in spinal surgery outcomes
      research is increasing. A number of variables collected by the American College
      of Surgeons National Surgical Quality Improvement Program (NSQIP) changed between
      2010 and 2011, coinciding with a rapid increase in the number of patients
      included per year. However, there has been limited study evaluating the effect
      that these changes may have on the results of outcomes studies. PURPOSE: The
      present study aimed to investigate the influence of changing data elements and
      growth of the NSQIP database on results of lumbar fusion outcomes studies. STUDY
      DESIGN/SETTING: This is a retrospective cohort study of prospectively collected
      data. PATIENT SAMPLE: The NSQIP database was retrospectively queried to identify
      19,755 patients who underwent elective posterior lumbar fusion surgery with or
      without interbody fusion between 2005 and 2014. Patients were split into two
      groups based on year of surgery: 2,802 from 2005 to 2010 and 16,953 from 2011 to
      2014. OUTCOME MEASURES: The occurrence of adverse events after discharge from the
      hospital, within postoperative day 30, was determined. METHODS: Preoperative
      characteristics and 30-day perioperative outcomes were compared between the era
      groups using bivariate analysis. To illustrate the effect of such changing data
      elements, the association between age and postoperative outcomes in the era
      groups was analyzed using multivariate Poisson regression. The present study had
      no funding sources, and there were no study-related conflicts of interest for any
      authors. RESULTS: There were significant differences between the era groups for a
      variety of preoperative characteristics. Postoperative events such blood
      transfusion and deep vein thrombosis were also significantly different between
      the era groups. For the 2005-2010 cohort, age was significantly associated with
      septic shock by multivariate analysis. For the 2011-2014 cohort, age was
      significantly associated with septic shock, urinary tract infection, blood
      transfusion, myocardial infarction, and extended length of stay. CONCLUSIONS: The
      NSQIP database has undergone substantial changes between 2005 and 2014. These
      changes may contribute to different results in analyses, such as the association
      between age and postoperative outcomes, when using older versus newer data.
      Conclusions from early studies using this database may warrant reconsideration.

PMID- 29649611
TI  - Predictors of adverse discharge disposition in adult spinal deformity and
      associated costs.
AB  - BACKGROUND CONTEXT: With advances in the understanding of adult spinal deformity
      (ASD), more complex osteotomy and fusion techniques are being implemented with
      increasing frequency. Patients undergoing ASD corrections infrequently require
      extended acute care, longer inpatient stays, and are discharged to supervised
      care. Given the necessity of value-based health care, identification of clinical
      indicators of adverse discharge disposition in ASD surgeries is paramount.
      PURPOSE: Using the nationwide and surgeon-created databases, the present study
      aimed to identify predictors of adverse discharge disposition after ASD surgeries
      and view the corresponding differences in charges. STUDY DESIGN/SETTING: This is
      a retrospective analysis of patients on the National Surgical Quality Improvement
      Program (NSQIP) database and of cost data from Medicare PearlDiver Database.
      PATIENT SAMPLE: Patients undergoing thoracolumbar surgery for correction of ASD
      were included in the study. OUTCOME MEASURES: Primary analysis was performed to
      compare patients discharged to home with patients who either expired or were
      discharged to locations other than home. Secondary analysis was performed to
      determine the cost differences across discharge groups. METHODS: Patients on
      NSQIP undergoing thoracolumbar ASD-corrective surgery with a primary diagnosis of
      scoliosis (ICD-9 code 737.x) and over the age of 18 were isolated. Predictors
      (demographic, clinical, and complications) of not-home (NH; rehab or skilled
      nursing facility) discharge were analyzed using binary logistic regression
      controlling for levels fused, decompressions, osteotomies, and revisions. Average
      30- and 90-day costs of care were reported in home, rehab, and skilled nursing
      facility discharge groups in patients undergoing 8+ level thoracolumbar fusion.
      RESULTS: A total of 1,978 patients undergoing lumbar ASD-corrective surgery were
      included for analysis (average age: 59.3 years, sex: 64% female). Average length
      of stay was 6.58 days. On multivariate regression analysis, age over 60 years
      (odds ratio [OR]: 0.28, confidence interval [CI]: 0.22-0.34) and female sex
      (p=.003) were independent predictors of adverse discharge status. Partially
      dependent preoperational functional status, defined as reliance on another person
      to complete some activities of daily living, increased likelihood of adverse
      discharge disposition (OR: 0.57, CI: 0.35-0.90). Despite controlling for all
      clinical variables except for the ones specific to each analysis, Smith-Petersen
      osteotomy (OR: 0.51, CI: 0.40-0.64), interbody device placement (OR: 0.80, CI:
      0.64-0.98), and fixation to the iliac (OR: 0.54, CI: 0.41-0.70) increased the
      likelihood of adverse discharge. Complications most associated with adverse
      discharge were urinary tract infections (OR: 0.34, CI: 0.21-0.57) and blood
      transfusions (OR: 0.42, CI: 0.34-0.52). Relative to home discharge, 30-day costs
      of care were +$21,061 more expensive in rehab discharges, but not different in
      skilled nursing facility discharges (+$5,791, p=.177). The 90-day costs of care
      were $23,815 in rehab discharges (p<.001), but again not different from skilled
      nursing facility discharges (+$6,091, p=.212). CONCLUSIONS: Discharge destination
      to rehabilitation has a significant impact on the cost of thoracolumbar ASD
      surgeries. Patient selection can predict patients at higher risk of discharges to
      rehab or skilled nursing facility.

PMID- 29649612
TI  - Independent predictors of spinal epidural abscess recurrence.
AB  - BACKGROUND CONTEXT: Recurrence of spinal epidural abscess (SEA) after treatment
      is an important cause of continued morbidity for patients. PURPOSE: The purpose
      of this study was to identify independent predictors of recurrence of SEA. STUDY
      DESIGN/SETTING: This was a retrospective, case-control study. PATIENT SAMPLE:
      Patients 18 years or older with a diagnosis of SEA admitted to our hospital
      system during the study period were included in the study sample. OUTCOME
      MEASURES: The outcome measure was recurrence of SEA, defined as a reaccumulation
      of pus or infected granulation tissue in the epidural space after initial
      treatment. METHODS: All patients older than 18 years admitted to our hospital
      system with a diagnosis of SEA from 1993 to 2016 were identified, and explanatory
      variables and outcomes were collected retrospectively. Patients 18 years or older
      diagnosed with SEA were included. We excluded patients whose treatment was
      initiated at an outside institution. Bivariate and multivariate analyses were
      performed to identify independent predictors of recurrence. RESULTS: We
      identified 1,053 patients with SEA. We only considered patients to be recurrence
      free if they had no documented recurrence with greater than 20 weeks of follow
      up. Five hundred thirty-four patients were recurrence-free and 38 had documented
      recurrence, yielding 572 patients who were included in this analysis. Bivariate
      and multivariate analyses identified three independent predictors of recurrence:
      history of intravenous drug use, fecal incontinence or retention, and local
      spinal wound infection. CONCLUSIONS: Patients with SEA who have a history of
      intravenous drug use, bowel dysfunction at presentation, or concurrent local
      spinal wound infection are at increased risk of disease recurrence. These
      patients ought to be closely followed up after discharge, with frequent serial
      imaging and aggressive antibiotic treatment.

PMID- 29649613
TI  - Anxiety and depression in spine surgery-a systematic integrative review.
AB  - BACKGROUND: Symptoms of preoperative anxiety and depression occur in
      approximately one-third of patients with chronic back pain undergoing surgery. In
      the last 2 decades, several studies have established that preoperative anxiety
      and depression are important outcome predictors of greater pain and physical
      impairments, and lower health-related quality of life in patients undergoing
      spine surgery. To accommodate symptoms of anxiety and depression and thereby
      better surgical outcomes, we need to identify factors associated with these
      symptoms. PURPOSE: We aimed to identify factors associated with symptoms of
      anxiety and depression in adults both before and after undergoing spinal surgery.
      STUDY DESIGN: An integrative literature review was carried out. METHODS: The
      independent charity Helsefonden supported this literature review by contributing
      $45,000 to remunerate a dedicated investigator. A systematic literature search
      was conducted in PubMed, CINAHL, PsycINFO, Embase, Scopus, Cochrane, and Web of
      Science. A three-step selection and assessment process was conducted; titles and
      abstracts of 1,124 articles were skimmed for relevance and of these, 53 articles
      were found to be of relevance and were read in full. Articles not meeting the
      inclusion criteria (n=26) were excluded. The 31 articles were critically
      appraised for methodological validity; 14 of these were synthesized and analyzed
      using a convergent qualitative design to transform both qualitative and
      quantitative articles into qualitative findings. RESULTS: Fourteen studies were
      included, reporting results based on 4,833 participants, 3,017 men and 1,816
      women, whose mean age was approximately 49 years. From these results, we
      extracted 75 individual findings, which we then divided into five categories of
      factors associated with anxiety and depression both before and after undergoing
      spine surgery: pain, information, disability, employment, and mental health.
      CONCLUSIONS: Five categories of interacting factors that influenced symptoms of
      anxiety and depression both before and after surgery were identified: pain, lack
      of information, disability, return to work, and mental health. Information
      appears to have a regulating effect on anxiety and depression.

PMID- 29649614
TI  - Missing data treatments matter: an analysis of multiple imputation for anterior
      cervical discectomy and fusion procedures.
AB  - BACKGROUND CONTEXT: The presence of missing data is a limitation of large
      datasets, including the National Surgical Quality Improvement Program (NSQIP). In
      addressing this issue, most studies use complete case analysis, which excludes
      cases with missing data, thus potentially introducing selection bias. Multiple
      imputation, a statistically rigorous approach that approximates missing data and
      preserves sample size, may be an improvement over complete case analysis.
      PURPOSE: The present study aims to evaluate the impact of using multiple
      imputation in comparison with complete case analysis for assessing the
      associations between preoperative laboratory values and adverse outcomes
      following anterior cervical discectomy and fusion (ACDF) procedures. STUDY
      DESIGN/SETTING: This is a retrospective review of prospectively collected data.
      PATIENT SAMPLE: Patients undergoing one-level ACDF were identified in NSQIP 2012
      2015. OUTCOME MEASURES: Perioperative adverse outcome variables assessed included
      the occurrence of any adverse event, severe adverse events, and hospital
      readmission. METHODS: Missing preoperative albumin and hematocrit values were
      handled using complete case analysis and multiple imputation. These preoperative
      laboratory levels were then tested for associations with 30-day postoperative
      outcomes using logistic regression. RESULTS: A total of 11,999 patients were
      included. Of this cohort, 63.5% of patients had missing preoperative albumin and
      9.9% had missing preoperative hematocrit. When using complete case analysis, only
      4,311 patients were studied. The removed patients were significantly younger,
      healthier, of a common body mass index, and male. Logistic regression analysis
      failed to identify either preoperative hypoalbuminemia or preoperative anemia as
      significantly associated with adverse outcomes. When employing multiple
      imputation, all 11,999 patients were included. Preoperative hypoalbuminemia was
      significantly associated with the occurrence of any adverse event and severe
      adverse events. Preoperative anemia was significantly associated with the
      occurrence of any adverse event, severe adverse events, and hospital readmission.
      CONCLUSIONS: Multiple imputation is a rigorous statistical procedure that is
      being increasingly used to address missing values in large datasets. Using this
      technique for ACDF avoided the loss of cases that may have affected the
      representativeness and power of the study and led to different results than
      complete case analysis. Multiple imputation should be considered for future spine
      studies.

PMID- 29649616
TI  - Subgenome assignment in allopolyploids: challenges and future directions.
AB  - Whole genome duplications (WGDs), also known as polyploid events, have played a
      crucial role in the evolutionary success of angiosperms across recent and ancient
      timescales. A recurrent observation from the analysis of allopolyploids is that
      one of the parental subgenomes is generally more dominant, referred to as
      'subgenome dominance', based on higher gene content and expression patterns.
      Subgenome dominance has far reaching implications to research areas ranging from
      crop improvement efforts to evolutionary and ecological studies. However, the
      analysis of subgenome dominance in more ancient polyploids is complicated by a
      long history of homoeologous exchanges among subgenomes. Here, we will discuss
      how resulting homoeolog rearrangements and replacements have been ignored in
      previous studies and urge future studies to integrate phylogenetic approaches to
      assign homoeologs to parental subgenomes.

PMID- 29649615
TI  - Fever-related arrhythmic events in the multicenter Survey on Arrhythmic Events in
      Brugada Syndrome.
AB  - BACKGROUND: The literature on fever-related arrhythmic events (AEs) in Brugada
      syndrome (BrS) is currently limited to few case reports and small series.
      OBJECTIVE: The present study aimed to describe the characteristics of fever
      related AE in a large cohort of patients with BrS. METHODS: The Survey on
      Arrhythmic Events in Brugada Syndrome is a multicenter study on 678 patients with
      BrS with first AE documented at the time of aborted cardiac arrest (n = 426) or
      after prophylactic implantable cardioverter-defibrillator implantation (n = 252).
      RESULTS: In 35 of 588 patients (6%) with available information, the AE occurred
      during a febrile illness. Most of the 35 patients were male (80%), Caucasian
      (83%), and proband (70%). The mean age at the time of AE was 29 +/- 24 years
      (range 0.3-76 years). Most patients (80%) presented with aborted cardiac arrest
      and 6 (17%) with arrhythmic storm. Family history of sudden death, history of
      syncope, and spontaneous type 1 Brugada electrocardiogram were noted in 17%, 40%,
      and 71% of patients, respectively. Ventricular fibrillation was induced at
      electrophysiology study in 9 of 19 patients (47%). An SCN5A mutation was found in
      14 of 28 patients (50%). The highest proportion of fever-related AE was observed
      in the pediatric population (age <16 years), with a disproportionally higher
      event rate in the very young (age 0-5 years) (65%). Males were involved in all
      age groups and females only in the pediatric and elderly groups. Fever-related AE
      affected 17 Caucasians aged <24 years, but no Asians aged <24 years. CONCLUSION:
      The risk of fever-related AE in BrS markedly varies according to age group, sex,
      and ethnicity. Taking these factors into account could help the clinical
      management of patients with BrS with fever.

PMID- 29649617
TI  - Reversal of T Cell Exhaustion by the First Donor Lymphocyte Infusion Is
      Associated with the Persistently Effective Antileukemic Responses in Patients
      with Relapsed AML after Allo-HSCT.
AB  - Donor lymphocyte infusion (DLI) is an effective approach to treat acute
      myelogenous leukemia (AML) relapse after allogeneic hematopoietic stem cell
      transplantation (allo-HSCT) that significantly improves the survival of relapsed
      patients. However, the mechanism of an effective antileukemic response following
      DLI in AML relapse remains elusive. Here, we investigated the role of T cell
      exhaustion in AML relapse after allo-HSCT in prospective cohorts of 41 patients
      with the first AML relapse and 41 nonrelapsed AML control subjects after allo
      HSCT and determined whether DLI exerts effective antileukemic effects by
      reversing T cell exhaustion in the relapsed cohorts by detecting the phenotypes
      and functions of T cells using flow cytometry. We found that both CD4+ and CD8+ T
      cells experienced exhaustion with upregulated coexpression of PD-1 and Tim-3, and
      functional impairments in cytokine production, proliferation, and cytotoxic
      potentials. The reversal of T cell exhaustion by the first DLI is associated with
      persistent complete remission in relapsed AML patients. In addition, the reversal
      of T cell-exhausted status after successful DLI in bone marrow was concurrent
      with the mitigated inversion of CD4/CD8 T cell ratio. In conclusion, our study
      shows a clinical correlation between T cell exhaustion and AML relapse after allo
      HSCT, and uncovers the role of reversing T cell exhaustion in the antileukemic
      response by DLI and identifies possible immunological markers to evaluate and
      predict the graft-versus-leukemia effects induced by DLI.

PMID- 29649618
TI  - Preimplantation High-Resolution HLA Sequencing Using Next Generation Sequencing.
AB  - Hematopoietic stem cell transplantation (SCT) is the only therapeutic option in a
      number of heritable hematologic disorders and hematologic cancers. Many parents
      and families fail to find an HLA-identical donor for their affected family
      member. In such cases, conceiving for a "savior baby" remains the only option,
      especially in countries without access to national registries. By means of next
      generation sequencing (NGS) techniques, in a single experiment on single-cell
      products of in vitro fertilization, a healthy HLA-identical embryo can be
      implanted in the uterus of a concerned mother. The patient can therefore benefit
      from cord blood SCT along with confirming that the fetuses are not suffering from
      the heritable disorder. This study is an attempt to study the feasibility of
      preimplantation HLA sequencing on single blastomeres using NGS. Two couples who
      had previously undergone preimplantation genetic diagnosis of beta-thalassemia
      and their overall 10 embryos were studied and their 5 HLA loci were typed in high
      resolution through multiple displacement amplification and NGS of single cells.
      For 88.9% of the 90 HLA alleles, conclusive HLA typing in 4 digit sets was made.
      HLA alleles were typed; 1 ambiguity in the allelic group and 4 ambiguities in the
      protein level were observed that were then unraveled by haplotype analysis.
      Amplification efficiency was 93.3% with an allele drop-out (ADO) rate of 22.2% (6
      alleles dropped from a maximum of 27 possible ADOs). In this study the
      feasibility of a new method of preimplantation HLA sequencing via combining the
      state-of-the-art techniques used in single-cell whole genome amplification,
      preimplantation genetic diagnosis, and high-resolution HLA typing by NGS has been
      shown. This method can make preimplantation HLA sequencing a practicable
      technique in families desperate for an HLA-matched donor.

PMID- 29649619
TI  - Shared Decision-Making in Hematopoietic Stem Cell Transplantation for Sickle Cell
      Disease.

PMID- 29649620
TI  - Allogeneic Hematopoietic Stem Cell Transplantation Following the Use of
      Hypomethylating Agents among Patients with Relapsed or Refractory AML: Findings
      from an International Retrospective Study.
AB  - Patients with primary refractory or relapsed acute myeloid leukemia (RR-AML) have
      very poor prognosis. Due to limited treatment options, some patients are treated
      with hypomethylating agents (HMAs) due to their tolerability. Little is known
      about the role of allogeneic hematopoietic stem cell transplantation (HSCT)
      following HMA therapy in this setting. We retrospectively analyzed an
      international cohort of 655 RR-AML patients who received HMA therapy to study
      patterns and outcomes with HSCT. Only 37 patients (5.6%) patients underwent HSCT
      after HMA therapy. The conditioning regimen was myeloablative in 57% and
      nonmyeloablative in 43%. Patients received matched unrelated donor, matched
      sibling, haploidentical and mismatched unrelated HSCT in 56%, 24%, 16% and 4% of
      cases, respectively. Acute GvHD and chronic GvHD were observed in 40% and 17% of
      patients. While the median OS for the entire cohort of patients was 15.3 months
      (95% CI 9.5 - 21.7 months), OS reached 29.7 months (95% CI 7.01 - not-reached)
      for patients who achieved a complete remission (CR) to HMA and no intervening
      therapies between HMA therapy and HSCT. Our study suggests that HMA therapy can
      effectively bridge some patients with RR-AML to HSCT.

PMID- 29649622
TI  - Stick-slip motion and controlled filling speed by the geometric design of soft
      micro-channels.
AB  - HYPOTHESIS: Liquid can move by capillary action through interconnected porous
      materials, as in fabric or paper towels. Today mass transport is controlled by
      chemical modification. It is, however, possible to direct mass transport by
      geometrical modifications. It is here proposed that it is possible to tailor
      capillary flow speed in a model system of micro-channels by the angle, size and
      position of attached side channels. EXPERIMENTS: A flexible, rapid, and cost
      effective method is used to produce micro-channels in gels. It involves 3D
      printed moulds in which gels are cast. Open channels of micrometre size with
      several side channels on either one or two sides are produced with tilting angles
      of 10-170 degrees . On a horizontal plane the meniscus of water driven by surface
      tension is tracked in the main channel. FINDINGS: The presence of side channels
      on one side slowed down the speed of the meniscus in the main channel least.
      Channels having side channels on both sides with tilting angles of up to 30
      degrees  indicated tremendously slower flow, and the liquid exhibited a stick
      slip motion. Broader side channels decreased the speed more than thinner ones, as
      suggested by the hypothesis. Inertial forces are suggested to be important in
      branched channel systems studied here.

PMID- 29649623
TI  - SILAR controlled CdSe nanoparticles sensitized ZnO nanorods photoanode for solar
      cell application: Electrolyte effect.
AB  - Controlled growth of different sizes of cadmium selenide (CdSe) nanoparticles
      over well aligned ZnO nanorods have been performed using successive ionic layer
      adsorption and reaction (SILAR) technique at room temperature (27  degrees C) in
      order to form nano heterostructure solar cells. Deposition of compact layer of
      zinc oxide (ZnO) by SILAR technique on fluorine doped tin oxide (FTO) coated
      glass substrate followed by growth of vertically aligned ZnO nanorods array using
      chemical bath deposition (CBD) at low temperature (<100  degrees C). Different
      characterization techniques viz. X-ray diffractometer, UV-Vis spectrophotometer,
      field emission scanning electron microscopy, transmission electron microscopy and
      X-ray photoelectron spectroscopy have been used to know the structural, optical,
      morphological and compositional properties of synthesized nano heterostructure.
      The photovoltaic performance of the cells with variation in SILAR cycles for CdSe
      and with use of different electrolytes have been recorded as J-V characteristics
      and the maximum conversion efficiency of 0.63% have been attained with
      ferro/ferri cyanide electrolyte for 12 cycles CdSe coating over 1-D ZnO nanorods.

PMID- 29649625
TI  - Lumbar versus thoracic erector spinae plane block: Similar nomenclature,
      different mechanism of action.

PMID- 29649624
TI  - Halloysite nanotubes for efficient loading, stabilization and controlled release
      of insulin.
AB  - HYPOTHESIS: Oral insulin administration is not actually effective due to insulin
      rapid degradation, inactivation and digestion by proteolytic enzymes which
      results in low bioavailability. Moreover insulin is poorly permeable and lack of
      lipophilicity. These limits can be overcome by the loading of protein in some
      nanostructured carrier such as halloysite nanotubes (HNTs). EXPERIMENTS: Herein
      we propose an easy strategy to obtain HNT hybrid materials for the delivery of
      insulin. We report a detailed description on the thermal behavior and stability
      of insulin loaded and released from the HNTs hybrid by the combination of several
      techniques. FINDINGS: Release experiments of insulin from the HNTs revealed the
      efficacy of the nanocarrier. Circular Dichroism data evidenced that the released
      insulin exhibits its native-like secondary structure confirming the suitability
      of HNT/insulin as delivery system for at least three months. The loaded nanotubes
      were filled into chitosan matrix with the aim to prepare bionanocomposite films
      that can be used for transdermal delivery. This work puts forward an efficient
      strategy to prepare halloysite based nanocarriers containing insulin that could
      be employed in several biomedical applications. The detailed description of the
      prepared HNT/insulin hybrid represents a fundamental point for designing advanced
      delivery systems.

PMID- 29649621
TI  - Astrocyte-specific DJ-1 overexpression protects against rotenone-induced
      neurotoxicity in a rat model of Parkinson's disease.
AB  - DJ-1 is a redox-sensitive protein with several putative functions important in
      mitochondrial physiology, protein transcription, proteasome regulation, and
      chaperone activity. High levels of DJ-1 immunoreactivity are reported in
      astrocytes surrounding pathology associated with idiopathic Parkinson's disease,
      possibly reflecting the glial response to oxidative damage. Previous studies
      showed that astrocytic over-expression of DJ-1 in vitro prevented oxidative
      stress and mitochondrial dysfunction in primary neurons. Based on these
      observations, we developed a pseudotyped lentiviral gene transfer vector with
      specific tropism for CNS astrocytes in vivo to overexpress human DJ-1 protein in
      astroglial cells. Following vector delivery to the substantia nigra and striatum
      of adult Lewis rats, the DJ-1 transgene was expressed robustly and specifically
      within astrocytes. There was no observable transgene expression in neurons or
      other glial cell types. Three weeks after vector infusion, animals were exposed
      to rotenone to induce Parkinson's disease-like pathology, including loss of
      dopaminergic neurons, accumulation of endogenous alpha-synuclein, and
      neuroinflammation. Animals over-expressing hDJ-1 in astrocytes were protected
      from rotenone-induced neurodegeneration, and displayed a marked reduction in
      neuronal oxidative stress and microglial activation. In addition, alpha-synuclein
      accumulation and phosphorylation were decreased within substantia nigra
      dopaminergic neurons in DJ-1-transduced animals, and expression of LAMP-2A, a
      marker of chaperone mediated autophagy, was increased. Together, these data
      indicate that astrocyte-specific overexpression of hDJ-1 protects neighboring
      neurons against multiple pathologic features of Parkinson's disease and provides
      the first direct evidence in vivo of a cell non-autonomous neuroprotective
      function of astroglial DJ-1.

PMID- 29649626
TI  - Novel compounds TAD-1822-7-F2 and F5 inhibited HeLa cells growth through the
      JAK/Stat signaling pathway.
AB  - Cervical carcinoma remains the second most common malignancy with a high
      mortality rate among women worldwide. TAD-1822-7-F2 (F2) and TAD-1822-7-F5 (F5)
      are novel compounds synthesized on the chemical structure of taspine derivatives,
      and show an effective suppression for HeLa cells. Our study aims to confirm the
      potential targets of F2 and F5, and investigate the underlying mechanism of the
      inhibitory effect on HeLa cells. In this study, Real Time Cell Analysis and
      crystal violet staining assay were conducted to investigate the effect of F2 and
      F5 on HeLa cells proliferation. And the analytical methods of surface plasmon
      resonance and quartz crystal microbalance were established and employed to study
      the interaction between F2 and F5 and potential target protein JAK2, suggesting
      that both compounds have strong interaction with the JAK2 protein. Western blot
      analysis, immunofluorescence staining study and PCR was conducted to investigate
      the molecules of JAK/Stat signaling pathway. Interestingly, F2 and F5 showed
      diverse regulation for signaling molecules because of their different chemical
      structure. F2 increased the expression of JAK2 and downregulated the level of P
      JAK1 and P-JAK2, and decreased P-Stat3 (Ser727). While F5 could increase the
      expression of JAK2 and naturally decrease the phosphorylation of JAK1 and Tyk2,
      and decreased the expression of P-Stat6. Moreover, F2 and F5 showed the same
      downregulation on the P-Stat3 (Tyr705). Therefore, F2 and F5 could target the
      JAK2 protein and prevent the phosphorylation of JAKs to suppress the
      phosphorylation of the downstream effector Stats, which suggested that F2 and F5
      have great potential to be the inhibitors of the JAK/Stat signaling pathway.

PMID- 29649627
TI  - Overexpression of HIPK2 attenuates spinal cord injury in rats by modulating
      apoptosis, oxidative stress, and inflammation.
AB  - HIPK2 is considered to be a tumor suppressor. It also has been implicated in
      several functions such as apoptosis and inflammation that are linked to spinal
      cord injury (SCI). However, whether HIPK2 ameliorates the neurological pain of
      SCI remains unclear. Here, we investigated the effects of HIPK2 on neurological
      function, oxidative stress, levels of inflammatory cytokines and expression of
      Bcl-2/Bax in an SCI model. Firstly, we evaluated the therapeutic effects of HIPK2
      on neurological pain in the SCI rat using the Basso, Beattie and Bresnahan scores
      and H & E staining. Overexpression of HIPK2 significantly elevated the levels of
      brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic
      factor (GDNF), and reduced the mRNA expression of Nogo-A and RhoA in SCI rats.
      Furthermore, terminal deoxynucleotidyl transferase-mediated dUTP nick end
      labeling (TUNEL) assays showed that overexpression of HIPK2 significantly reduced
      the number of apoptotic cells. Overexpression of HIPK2 also decreased expression
      of Bax and Caspase-3 and elevated expression of Bcl-2 in the SCI model,
      indicating that HIPK2 exhibited its protective activity by inhibiting SCI-induced
      apoptosis. Then, we measured the serum concentrations of malondialdehyde (MDA),
      superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX).
      We also determined the mRNA and protein levels of nuclear factor-kappaB p65 unit,
      tumor necrosis factor-alpha (TNF-alpha), and interleukin (IL)-1beta. HIPK2
      overexpression reduced oxidative stress and the levels of inflammatory cytokines
      compared with SCI control animals. Additionally, acetylation of HIPK2 was reduced
      in SCI rats. Overexpression of HIPK2 could enhance autophagy by elevating the
      expression of Beclin-1 and LC3-II while autophagy is regarded as a beneficial
      regulator to improve spinal cord injury. Together, overexpression of HIPK2
      improved contusive SCI induced pain by modulating oxidative stress, Bcl-2 and Bax
      signaling, and inflammation, and also regulating autophagy.

PMID- 29649628
TI  - Eupatilin inhibits adipogenesis through suppression of PPARgamma activity in 3T3
      L1 cells.
AB  - Eupatilin (5,7-dihydroxy-3',4',6-trimethoxyflavone) is a flavonoid compound from
      Artemisia species that possesses beneficial biological activities such as anti
      cancer, anti-oxidation, and anti-inflammatory activities. However, an anti
      adipogenic effect has not yet been reported. In this study, we found that
      eupatilin significantly inhibited the adipogenesis of 3T3-L1 adipocytes.
      Eupatilin decreased intracellular lipid accumulation and suppressed the
      expression level of key adipogenic regulators in 3T3-L1 adipocytes, including
      peroxisome proliferator-activated receptor gamma (PPARgamma) and CCAAT-enhancer
      binding protein alpha (C/EBPalpha), in a concentration-dependent manner. These
      results show that eupatilin significantly inhibits 3T3-L1 cell differentiation
      and suggest that it has potential as a novel anti-obesity therapy.

PMID- 29649629
TI  - Qingchangligan formula alleviates acute liver injury by attenuating extracellular
      histone-associated inflammation.
AB  - Qingchangligan formula (QCLGF) is a traditional Chinese medicine that has
      exhibited remarkable clinical efficacy for patients with acute-on-chronic liver
      failure (ACLF). However, the hepatoprotective mechanisms of QCLGF are not
      completely understood. Extracellular histones were recently identified as the
      novel inflammatory mediators involved in the pathogenesis of acute liver injury.
      This study aimed to investigate whether QCLGF provides hepatoprotection by
      targeting extracellular histones. We showed that QCLGF significantly improved the
      survival rate of the ConA-treated mice, ameliorated hepatotoxicity, and markedly
      decreased the levels of extracellular histones and the associated cytokines. We
      further demonstrated that QCLGF attenuated systemic inflammation by inhibiting
      the mitogen-activated protein kinase (MAPK) signaling pathway. In addition,
      exogenous histones induced a significant HL-7702 cell damage, which could be
      prevented by administration of QCLGF. Lastly, we observed that extracellular
      histones and the associated cytokines were consistently lower in ACLF patients
      receiving conventional medical therapy plus QCLGF than in patients receiving only
      conventional medical therapy. Collectively, these results provide evidence that
      QCLGF has therapeutic potentials for treating ACLF, which may be due to its
      ability to interfere with extracellular histone-mediated cellular damage and
      systemic inflammation.

PMID- 29649630
TI  - Standard CD44 modulates YAP1 through a positive feedback loop in hepatocellular
      carcinoma.
AB  - High expression levels of CD44 and YAP have been identified as poor prognostic
      factors in hepatocellular carcinoma (HCC). However, the mechanistic relationship
      between CD44 and YAP during HCC tumorigenesis remains largely unknown. To
      investigate the mutual regulation between standard CD44 (CD44S) and YAP1 in HCC
      cell lines and tissue samples, CD44S and YAP1 expression in 40 pairs of tumor
      samples and matched distal normal tissues from HCC patients was examined by
      immunohistochemical staining. High expression of either CD44S or YAP1 was
      associated with a younger age and worse pathology grade. In addition, high levels
      of CD44S and YAP1 were associated with increased vascular invasion and more
      severe liver cirrhosis, respectively. CD44S expression was positively correlated
      with YAP1 expression in these HCC tissues. In vitro experiments suggested that
      CD44S could positively regulate the expression of YAP1 and its target genes via
      the PI3K/Akt pathway in HCC cells. Moreover, CD44S is regulated by the YAP1/TEAD
      axis. These results reveal a novel positive feedback loop involving CD44S and
      YAP1, in which CD44S functions as both an upstream regulator and a downstream
      effector of YAP1 in HCC. This feedback loop might constitute a broadly conserved
      module for regulating cell proliferation and invasion during HCC tumorigenesis.
      Blocking this positive feedback loop that involves CD44S and YAP1 might represent
      a new approach for HCC treatment.

PMID- 29649632
TI  - Identification of runt family genes involved in planarian regeneration and tissue
      homeostasis.
AB  - The runt family genes play important roles in physiological processes in
      eukaryotic organisms by regulation of protein transcription, such as
      hematopoietic system, proliferation of gastric epithelial cells and neural
      development. However, it remains unclear about the specific functions of these
      genes. In this study, the full-length cDNA sequences of two runt genes are first
      cloned from Dugesia japonica, and their roles are investigated by WISH and RNAi.
      The results show that: (1) the Djrunts are conserved during evolution; (2) the
      Djrunts mRNA are widely expressed in intact and regenerative worms, and their
      expression levels are up-regulated significantly on day 1 after amputation; (3)
      loss of Djrunts function lead to lysis or regeneration failure in the intact and
      regenerating worms. Overall, the data suggests that Djrunts play important roles
      in regeneration and homeostatic maintenance in planarians.

PMID- 29649631
TI  - Simultaneous Risk Factor Control Using Telehealth to slOw Progression of Diabetic
      Kidney Disease (STOP-DKD) study: Protocol and baseline characteristics of a
      randomized controlled trial.
AB  - : Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease
      (ESKD) in the United States. Multiple risk factors contribute to DKD development,
      yet few interventions target more than a single DKD risk factor at a time. This
      manuscript describes the study protocol, recruitment, and baseline participant
      characteristics for the Simultaneous Risk Factor Control Using Telehealth to slOw
      Progression of Diabetic Kidney Disease (STOP-DKD) study. The STOP-DKD study is a
      randomized controlled trial designed to evaluate the effectiveness of a
      multifactorial behavioral and medication management intervention to mitigate
      kidney function decline at 3 years compared to usual care. The intervention
      consists of up to 36 monthly educational modules delivered via telephone by a
      study pharmacist, home blood pressure monitoring, and medication management
      recommendations delivered electronically to primary care physicians. Patients
      seen at seven primary care clinics in North Carolina, with diabetes and [1]
      uncontrolled hypertension and [2] evidence of kidney dysfunction (albuminuria or
      reduced estimated glomerular filtration rate [eGFR]) were eligible to
      participate. Study recruitment completed in December 2014. Of the 281
      participants randomized, mean age at baseline was 61.9; 52% were male, 56% were
      Black, and most were high school graduates (89%). Baseline co-morbidity was high-
      mean blood pressure was 134/76 mmHg, mean body mass index was 35.7 kg/m2, mean
      eGFR was 80.7 ml/min/1.73 m2, and mean glycated hemoglobin was 8.0%. Experiences
      of recruiting and implementing a comprehensive DKD program to individuals at high
      risk seen in the primary care setting are provided. TRIAL REGISTRATION:
      NCT01829256.

PMID- 29649633
TI  - Circulating Wnt inhibitory factor 1 levels are associated with development of
      cardiovascular disease.
AB  - BACKGROUND AND AIMS: Wnt signaling is involved in atherosclerotic plaque
      formation directly and indirectly by modulating cardiovascular risk factors. We
      investigated whether circulating concentrations of Wnt inhibitors are associated
      with cardiovascular events in subjects with intermediate cardiovascular risk.
      METHODS: 904 non-diabetic subjects participating in the SAPHIR study were
      assessed. In the SAPHIR study, middle-aged women without overt atherosclerotic
      disease at study entry were followed up for 10 years. 88 patients of our study
      cohort developed cardiovascular disease at follow-up (CVD group). Subjects of the
      CVD group were 1:2 case-control matched for age, sex, BMI and smoking behavior
      with subjects without overt cardiovascular disease after a 10 year-follow-up
      (control group). 18 patients of the CVD group and 19 subjects of the control
      group were retrospectively excluded due to fulfilling exclusion criteria.
      Baseline circulating sclerostin, dickkopf (DKK)-1, secreted frizzled-related
      protein (SFRP)-1 and Wnt inhibitory factor (WIF)-1 levels were assessed by ELISA.
      RESULTS: Baseline systemic SFRP-1 and WIF-1 levels were significantly higher in
      patients with cardiovascular events (n = 70) when compared to healthy controls (n
      = 157) while DKK-1 and sclerostin levels were similar in both groups. Logistic
      regression analysis revealed WIF-1 as a significant predictor of future
      cardiovascular events. CONCLUSIONS: Our data suggest that increased SFRP-1 and
      WIF-1 levels precede the development of symptomatic atherosclerotic disease.
      Assessment of systemic WIF-1 levels, which turned out to be independently
      associated with CVD, might help to early identify patients at intermediate
      cardiovascular risk.

PMID- 29649635
TI  - Co-delivery of docetaxel and gemcitabine by anacardic acid modified self
      assembled albumin nanoparticles for effective breast cancer management.
AB  - : In the present study, we have modified bovine serum albumin (BSA) by covalently
      conjugating with anacardic acid (AA) and gemcitabine (GEM) and further used for
      development of docetaxel (DTX) loaded nanoparticles (AA-GEM-BSA NPs). AA is
      supposed to provide tumor targeting through VEGF receptors overexpressed in
      tumors, while the combination of GEM and DTX is supposed to provide synergistic
      activity by targeting multiple pathways. The conjugate was synthesized via
      carbodiimide chemistry and characterized by 1H NMR, FTIR, MALDI-TOF and elemental
      analysis. Conformational changes owing to conjugation of AA and GEM were
      estimated via fluorescence, Raman and CD spectroscopy, while changes in
      physiochemical properties were studied by differential scanning calorimetry
      (DSC), thermogravimetry (TGA) and contact angle goniometry (CAG). Synthesized
      conjugate was further transformed into DTX loaded NPs and freeze dried. Scanning
      Electron Microscopy (SEM) and Atomic Force Microscopy (AFM) demonstrated
      formation of spherical NPs having particle size, 163 +/- 8 nm, PDI, 0.13 +/- 0.09
      and ZP, -27 +/- 1 mV. Cellular uptake in MCF-7 and MDA-MB-231 revealed hNTs,
      OATP1B3 independent, clathrin mediated internalization followed via nuclear co
      localization of C-6 loaded AA-GEM-BSA NPs, responsible for significantly higher
      apoptosis index. Pharmacokinetic profile of DTX loaded AA-GEM-BSA NPs revealed
      6.12 and 3.27-fold and 6.28 and 8.9-fold higher AUC and T1/2 values of DTX and
      GEM as compared to Taxotere(r) and Gemzar(r), respectively. Interestingly, the
      developed NPs were found safe with no marked effect on RBCs, lower hepato and
      nephro toxicity. Data in hand suggest promising potential of developed NPs in
      ameliorating the pharmacokinetic and therapeutic profile of combinatorial regimen
      of DTX and GEM. STATEMENT OF SIGNIFICANCE: The present report is the original
      state of art technology to selectively target dual drug (DTX and GEM) loaded BSA
      NPs via exploring tumor targeting potential of AA, having high affinity towards
      VEGF receptors (angiogenesis marker) overexpressed in tumor. The AA and GEM bio
      conjugated BSA was synthesized and further used to develop DTX loaded
      nanoparticles (AA-GEM-BSA NPs). The optimized NPs were further evaluated via
      extensive in vitro and in vivo studies, demonstrating ameliorated cellular
      uptake, pharmacokinetic and toxicity profile of drugs. Conclusively, DTX loaded
      AA-GEM-BSA NPs, holds promising potential in increasing the therapeutic
      efficiency of drugs and overcoming solvent and drug mediated side effects and can
      be explored further as a scalable platform technology for difficult to deliver
      drugs.

PMID- 29649634
TI  - Injectable, porous, biohybrid hydrogels incorporating decellularized tissue
      components for soft tissue applications.
AB  - : Biodegradable injectable hydrogels have been extensively studied and evaluated
      in various medical applications such as for bulking agents, drug delivery
      reservoirs, temporary barriers, adhesives, and cell delivery matrices. Where
      injectable hydrogels are intended to facilitate a healing response, it may be
      desirable to encourage rapid cellular infiltration into the hydrogel volume from
      the tissue surrounding the injection site. In this study, we developed a platform
      technique to rapidly form pores in a thermally responsive injectable hydrogel,
      poly(NIPAAm-co-VP-co-MAPLA) by using mannitol particles as porogens. In a rat
      hindlimb muscle injection model, hydrogels incorporating porosity had
      significantly accelerated cellular infiltration. To influence the inflammatory
      response to the injected hydrogel, enzymatically digested urinary bladder matrix
      (UBM) was mixed with the solubilized hydrogel. The presence of UBM was associated
      with greater polarization of the recruited macrophage population to the M2
      phenotype, indicating a more constructive foreign body response. The hybrid
      hydrogel positively affected the wound healing outcomes of defects in rabbit
      adipose tissue with negligible inflammation and fibrosis, whereas scar formation
      and chronic inflammation were observed with autotransplantation and in saline
      injected groups. These results demonstrate the value of combining the effects of
      promoting cell infiltration and mediating the foreign body response for improved
      biomaterials options soft tissue defect filling applications. STATEMENT OF
      SIGNIFICANCE: Our objective was to develop a fabrication process to create porous
      injectable hydrogels incorporating decellularized tissue digest material. This
      new hydrogel material was expected to exhibit faster cellular infiltration and a
      greater extent of pro-M2 macrophage polarization compared to control groups not
      incorporating each of the functional components. Poly(NIPAAm-co-VP-co-MAPLA) was
      chosen as the representative thermoresponsive hydrogel, and mannitol particles
      and digested urinary bladder matrix (UBM) were selected as the porogen and the
      bioactive decellularized material components respectively. In rat hindlimb
      intramuscular injection models, this new hydrogel material induced more rapid
      cellular infiltration and a greater extent of M2 macrophage polarization compared
      to control groups not incorporating all of the functional components. The hybrid
      hydrogel positively affected the wound healing outcomes of defects in rabbit
      adipose tissue with negligible inflammation and fibrosis, whereas scar formation
      and chronic inflammation were observed with autotransplantation and in saline
      injected groups. The methodology of this report provides a straightforward and
      convenient mechanism to promote cell infiltration and mediate foreign body
      response in injectable hydrogels for soft tissue applications. We believe that
      the readership of Acta Biomaterialia will find the work of interest both for its
      specific results and general translatability of the findings.

PMID- 29649636
TI  - A microfluidic oxygen sink to create a targeted cellular hypoxic microenvironment
      under ambient atmospheric conditions.
AB  - : Physiological oxygen levels within the tissue microenvironment are usually
      lower than 14%, in stem cell niches these levels can be as low as 0-1%. In cell
      cultures, such low oxygen levels are usually mimicked by altering the global
      culture environment either by O2 removal (vacuum or oxygen absorption) or by N2
      supplementation for O2 replacement. To generate a targeted cellular hypoxic
      microenvironment under ambient atmospheric conditions, we characterised the
      ability of the dissolved oxygen-depleting sodium sulfite to generate an in-liquid
      oxygen sink. We utilised a microfluidic design to place the cultured cells in the
      vertical oxygen gradient and to physically separate the cells from the liquid. We
      demonstrate generation of a chemical in-liquid oxygen sink that modifies the
      surrounding O2 concentrations. O2 level control in the sink-generated hypoxia
      gradient is achievable by varying the thickness of the polydimethylsiloxane
      membrane. We show that intracellular hypoxia and hypoxia response element
      dependent signalling is instigated in cells exposed to the microfluidic in-liquid
      O2 sink-generated hypoxia gradient. Moreover, we show that microfluidic flow
      controls site-specific microenvironmental kinetics of the chemical O2 sink
      reaction, which enables generation of intermittent hypoxia/re-oxygenation cycles.
      The microfluidic O2 sink chip targets hypoxia to the cell culture
      microenvironment exposed to the microfluidic channel architecture solely by
      depleting O2 while other sites in the same culture well remain unaffected. Thus,
      responses of both hypoxic and bystander cells can be characterised. Moreover,
      control of microfluidic flow enables generation of intermittent hypoxia or
      hypoxia/re-oxygenation cycles. STATEMENT OF SIGNIFICANCE: Specific manipulation
      of oxygen concentrations in cultured cells' microenvironment is important when
      mimicking low-oxygen tissue conditions and pathologies such as tissue infarction
      or cancer. We utilised a sodium sulfite-based in-liquid chemical reaction to
      consume dissolved oxygen. When this liquid was pumped into a microfluidic
      channel, lowered oxygen levels could be measured outside the channel through a
      polydimethylsiloxane PDMS membrane allowing only for gaseous exchange. We then
      utilised this setup to deplete oxygen from the microenvironment of cultured
      cells, and showed that cells responded to hypoxia on molecular level. Our setup
      can be used for specifically removing oxygen from the cell culture
      microenvironment for experimental purposes and for generating a low oxygen
      environment that better mimics the cells' original tissue environments.

PMID- 29649637
TI  - Angiogenesis impairment by the NADPH oxidase-triggered oxidative stress at the
      bone-implant interface: Critical mechanisms and therapeutic targets for implant
      failure under hyperglycemic conditions in diabetes.
AB  - : Mechanism underlying the diabetes-induced poor osteointegration of implants
      remains elusive, making it a challenge to develop corresponding solutions. Here,
      we studied the role of angiogenesis in the diabetes-induced poor bone repair at
      the bone-implant interface (BII) and the related mechanisms. In vivo, titanium
      screws were implanted in the femurs of mice, and, in vitro, vascular endothelial
      cell (VEC) was cultured on titanium surface. Results showed that, compared with
      normal milieu (NM), diabetic milieu (DM) led to angiogenesis inhibition around
      implants which resulted in reduced osteoprogenitors and poor bone formation on
      BII in vivo. In vitro, DM caused significant increase of NADPH oxidases (NOX),
      dysfunction of mitochondria and overproduction of reactive oxygen species (ROS)
      in VEC on titanium surface, inducing obvious cell dysfunction. Both Mito-TEMPO
      (Mito, a mitochondria-targeted ROS antagonist) and apocynin (APO, a NOX
      inhibitor) effectively attenuated the oxidative stress and dysfunction of VEC,
      with the beneficial effects of APO significantly better than those of Mito.
      Further study showed that the diabetes-induced metabolic disturbance of VEC was
      significantly related to the increase of advanced glycation end products (AGEs)
      at the BII. Our results suggested that the AGEs-related and NOX-triggered
      cellular oxidative stress leads to VEC dysfunction and angiogenesis impairment at
      the BII, which plays a critical role in the compromised implant osteointegration
      under diabetic conditions. These demonstrated new insights into the BII in
      pathological states and also provided NOX and AGEs as promising therapeutic
      targets for developing novel implant materials to accelerate the angiogenesis and
      osteointegration of implants in diabetic patients with hyperglycemia. STATEMENT
      OF SIGNIFICANCE: The high failure rate of bone implants in diabetic patients
      causes patients terrible pain and limits the clinical application of implant
      materials. The mechanism underlying this phenomenon needs elucidation so that it
      would be possible to develop corresponding solutions. Our study demonstrated that
      the AGEs-related and NOX-triggered oxidative stress of VEC leads to angiogenesis
      impairment at the bone-implant interface (BII) in diabetes. These are critical
      mechanisms underlying the compromised implant osteointegration in diabetic
      hyperglycemia. These provide new insights into the BII in diseased states and
      also suggest NOX and AGEs as crucial therapeutic targets for developing novel
      implant materials which could modulate the oxidative stress on BII to get
      improved osteointegration and reduced implant failure, especially in diabetic
      patients.

PMID- 29649638
TI  - Ultrafine heat-induced structural perturbations of bone mineral at the individual
      nanocrystal level.
AB  - : The nanoscale characteristics of the mineral phase in bone tissue such as
      nanocrystal size, organization, structure and composition have been identified as
      potential markers of bone quality. However, such characterization remains
      challenging since it requires combining structural analysis and imaging
      modalities with nanoscale precision. In this paper, we report the first
      application of automated crystal orientation mapping using transmission electron
      microscopy (ACOM-TEM) to the structural analysis of bone mineral at the
      individual nanocrystal level. By controlling the nanocrystal growth of a cortical
      bovine bone model artificially heated up to 1000  degrees C, we highlight the
      potential of this technique. We thus show that the combination of sample mapping
      by scanning and the crystallographic information derived from the collected
      electron diffraction patterns provides a more rigorous analysis of the mineral
      nanostructure than standard TEM. In particular, we demonstrate that nanocrystal
      orientation maps yield valuable information for dimensional analysis.
      Furthermore, we show that ACOM-TEM has sufficient sensitivity to distinguish
      between phases with close crystal structures and we address unresolved questions
      regarding the existence of a hexagonal to monoclinic phase transition induced by
      heating. This first study therefore opens new perspectives in bone
      characterization at the nanoscale, a daunting challenge in the biomedical and
      archaeological fields, which could also prove particularly useful to study the
      mineral characteristics of tissue grown at the interface with biomaterials
      implants. STATEMENT OF SIGNIFICANCE: In this paper, we propose a new approach to
      assess the mineral properties of bone at the individual nanocrystal level, a
      major challenge for decades. We use a modified Transmission Electron Microscopy
      acquisition mode to perform an Automated Crystal Orientation Mapping (ACOM-TEM)
      by analyzing electron diffraction patterns. We tune the mineral nanocrystal size
      by heating a model bovine bone system and show that this method allows precisely
      assessing the mineral nanocrystal size, orientation and crystallographic phase.
      ACOM-TEM therefore has sufficient sensitivity to solve problems that couldn't be
      answered using X-ray diffraction. We thus revisit the fine mechanisms of bone
      nanocrystal growth upon heating, a process currently used for bone graft
      manufacturing, also of practical interest for forensic science and archaeology.

PMID- 29649639
TI  - Cobalt (II) ions and nanoparticles induce macrophage retention by ROS-mediated
      down-regulation of RhoA expression.
AB  - : Histological assessments of synovial tissues from patients with failed CoCr
      alloy hip prostheses demonstrate extensive infiltration and accumulation of
      macrophages, often loaded with large quantities of particulate debris. The
      resulting adverse reaction to metal debris (ARMD) frequently leads to early joint
      revision. Inflammatory response starts with the recruitment of immune cells and
      requires the egress of macrophages from the inflamed site for resolution of the
      reaction. Metal ions (Co2+ and Cr3+) have been shown to stimulate the migration
      of T lymphocytes but their effects on macrophages motility are still poorly
      understood. To elucidate this, we studied in vitro and in vivo macrophage
      migration during exposure to cobalt and chromium ions and nanoparticles. We found
      that cobalt but not chromium significantly reduces macrophage motility. This
      involves increase in cell spreading, formation of intracellular podosome-type
      adhesion structures and enhanced cell adhesion to the extracellular matrix (ECM).
      The formation of podosomes was also associated with the production and activation
      of matrix metalloproteinase-9 (MMP9) and enhanced ECM degradation. We showed that
      these were driven by the down-regulation of RhoA signalling through the
      generation of reactive oxygen species (ROS). These novel findings reveal the key
      mechanisms driving the wear/corrosion metallic byproducts-induced inflammatory
      response at non-toxic concentrations. STATEMENT OF SIGNIFICANCE: Adverse tissue
      responses to metal wear and corrosion products from CoCr alloy implants remain a
      great challenge to surgeons and patients. Macrophages are the key regulators of
      these adverse responses to the ions and debris generated. We demonstrated that
      cobalt, rather than chromium, causes macrophage retention by restructuring the
      cytoskeleton and inhibiting cell migration via ROS production that affects Rho
      Family GTPase. This distinctive effect of cobalt on macrophage behaviour can help
      us understand the pathogenesis of ARMD and the cellular response to cobalt based
      alloys, which provide useful information for future implant design and
      biocompatibility testing.

PMID- 29649641
TI  - Hydrogel derived from porcine decellularized nerve tissue as a promising
      biomaterial for repairing peripheral nerve defects.
AB  - : Decellularized matrix hydrogels derived from tissues or organs have been used
      for tissue repair due to their biocompatibility, tunability, and tissue-specific
      extracellular matrix (ECM) components. However, the preparation of decellularized
      peripheral nerve matrix hydrogels and their use to repair nerve defects have not
      been reported. Here, we developed a hydrogel from porcine decellularized nerve
      matrix (pDNM-G), which was confirmed to have minimal DNA content and retain
      collagen and glycosaminoglycans content, thereby allowing gelatinization. The
      pDNM-G exhibited a nanofibrous structure similar to that of natural ECM, and a
      ~280-Pa storage modulus at 10 mg/mL similar to that of native neural tissues.
      Western blot and liquid chromatography tandem mass spectrometry analysis revealed
      that the pDNM-G consisted mostly of ECM proteins and contained primary ECM
      related proteins, including fibronectin and collagen I and IV). In vitro
      experiments showed that pDNM-G supported Schwann cell proliferation and preserved
      cell morphology. Additionally, in a 15-mm rat sciatic nerve defect model, pDNM-G
      was combined with electrospun poly(lactic-acid)-co-poly(trimethylene
      carbonate)conduits to bridge the defect, which did not elicit an adverse immune
      response and promoted the activation of M2 macrophages associated with a
      constructive remodeling response. Morphological analyses and electrophysiological
      and functional examinations revealed that the regenerative outcomes achieved by
      pDNM-G were superior to those by empty conduits and closed to those using rat
      decellularized nerve matrix allograft scaffolds. These findings indicated that
      pDNM-G, with its preserved ECM composition and nanofibrous structure, represents
      a promising biomaterial for peripheral nerve regeneration. STATEMENT OF
      SIGNIFICANCE: Decellularized nerve allografts have been widely used to treat
      peripheral nerve injury. However, given their limited availability and lack of
      bioactive factors, efforts have been made to improve the efficacy of
      decellularized nerve allograft for nerve regeneration, with limited success.
      Xenogeneic decellularized tissue matrices or hydrogels have been widely used for
      surgical applications owing to their ease of harvesting and low immunogenicity.
      Moreover, decellularized tissue matrix hydrogels show good biocompatibility and
      are highly tunable. In this study, we prepared a porcine decellularized nerve
      matrix (pDNM-G) and evaluated its potential for promoting nerve regeneration. Our
      results demonstrate that pDNM-G can support Schwann cell proliferation and
      peripheral nerve regeneration by means of residual primary extracellular matrix
      components and nano-fibrous structure features.

PMID- 29649640
TI  - A robust spectroscopic method for the determination of protein conformational
      composition - Application to the annealing of silk.
AB  - : The physical and mechanical properties of structural proteins such as silk
      fibroin can be modified by controlled conformational change, which is regularly
      monitored by Fourier transform infrared spectroscopy by peak fitting of the amide
      I band envelope. Although many variables affecting peak shape are well
      established, there is no fixed methodology to compare and follow secondary
      structural differences without significant operator input especially where low
      frequency spectral noise is a problem. The aim of this contribution is to
      establish a method for such analyses to be carried at high levels of autonomy to
      prevent subjective or erroneous fitting. A range of approaches was trialled with
      optimal peak parameters selected based on overall goodness of fit and
      reproducibility of fit of replicate sample spectra. The method was successfully
      tested against reference proteins having contrasting beta content and the
      rationale for parameter selection is presented. Further, we applied this method
      to measure the effect of conformational change on the energy of the amide I band
      of silk fibroin during annealing. Energy changes were ca. 400 kJ mol-1 of
      fibroin. To confirm that this energy change was a consequence of increased
      hydrogen bonding we used a Thioflavin T staining method typically used to
      identify beta aggregate type structures in amyloid plaques. We propose that the
      approach described herein can aid in the development of silk based materials for
      biomedical applications where tuning of the physical and mechanical properties of
      the silk are needed to guarantee optimum activity. STATEMENT OF SIGNIFICANCE: The
      physical and mechanical properties of proteins including silk fibroin can be
      modified by controlled structural change, which is regularly monitored by Fourier
      transform infrared spectroscopy (FTIR) by peak fitting of the amide I band.
      Currently there is no fixed methodology to compare and follow secondary
      structural differences without significant operator input leading to subjectivity
      and error. This contribution establishes a method for such analyses to be carried
      at high levels of autonomy applicable to a wide range of proteins and the
      conformational changes have been quantified as a single energy change output,
      which clearly shows the progression of the annealing process used. We propose
      that the approach can help in the development of silk based materials for
      biomedical applications where tuning of the physical and mechanical properties of
      the silk are needed to guarantee optimum activity.

PMID- 29649642
TI  - Is the Cervical Anterior Spinal Artery Compromised in Cervical Spondylotic
      Myelopathy Patients? Dual-Energy Computed Tomography Analysis of Cervical
      Anterior Spinal Artery.
AB  - OBJECTIVE: Cervical myelopathy is a common, acquired cause of spinal cord
      dysfunction in older patients. It is postulated that a hypoxic or ischemic
      environment secondary to chronic spinal cord compression plays an important role
      in the pathogenesis of myelopathy. This study aims to use dual-energy computed
      tomography (DECT) to assess the altered blood flow to the spinal cord in patients
      with cervical spondylotic myelopathy (CSM). To our knowledge, this study is the
      first to use DECT in identifying comprised anterior spinal artery blood flow in
      patients with CSM. METHODS: Fifty patients with single disc level CSM and 10
      volunteers without CSM underwent DECT of the cervical spine to analyze and
      compare the ASA. The neurologic status of each patient was evaluated
      preoperatively and postoperatively at 5 days, 1 month, and 6 months using the
      Japanese Orthopedic Association (JOA) score. All the patients with CSM underwent
      single-level anterior cervical discectomy and fusion, and at postoperative day 5,
      each patient underwent repeated DECT. The anterior spinal artery before and after
      surgery was compared in patients with CSM. The blood flow in terms of iodine
      content at a specific region of interest was measured in the axial CT of the
      volunteers group and in the preoperative and postoperative axial CT of patients
      with CSM. Correlations between change in blood flow and clinical improvement at
      each follow-up point were analyzed statistically. RESULTS: Iodine content (100
      mg/mL) was 14.2800 +/- 1.89527 at the C3/C4 disc level, 14.8280 +/- 1.83820 at
      the C4/C5 disc level, and 15.5000 +/- 2.41048 at the C5/C6 level. In patients
      with CSM, the preoperative iodine content (100 mg/mL) measured was 10.2621 +/-
      2.37396 in C3/C4 disc-level compression, 12.1438 +/- 1.63447 in C4/C5 disc-level
      compression, and 14.0620 +/- 2.44390 in C5/C6 disc-level compression.
      Postoperative iodine content (100 mg/mL) measurement changed to 13.78 +/- 2.77
      for the C3/C4 disc level, 14.16 +/- 1.90 for the C4/C5 disc level, and 15.14 +/-
      2.62 for the C5/C6 disc level. The JOA score was 13.650 preoperatively, 14.010 at
      5 days postoperatively, 14.630 at 1 month postoperatively, and 15.000 at 6 months
      postoperatively. The 1- and 6-month correlation ratios between the JOA and change
      in blood flow were statistically significant, with an r value of 0.746 (P < 0.05)
      and 0.760 (P < 0.05), respectively. CONCLUSIONS: This study provided evidence for
      the benefit of DECT as a radiographic tool for identifying the compromised
      cervical anterior spinal artery in patients with CSM. We believe that DECT is the
      one of the best radiographic tools available to provide an objective screening
      tool to detect compromised blood flow in patients with CSM.

PMID- 29649643
TI  - Estimating the Global Incidence of Aneurysmal Subarachnoid Hemorrhage: A
      Systematic Review for Central Nervous System Vascular Lesions and Meta-Analysis
      of Ruptured Aneurysms.
AB  - INTRODUCTION: There is increasing acknowledgement that surgical care is important
      in global health initiatives. In particular, neurosurgical care is as limited as
      1 per 10 million people in parts of the world. We performed a systematic
      literature review to examine the worldwide incidence of central nervous system
      vascular lesions and a meta-analysis of aneurysmal subarachnoid hemorrhage (aSAH)
      to define the disease burden and inform neurosurgical global health efforts.
      METHODS: A systematic review and meta-analysis were conducted according to the
      Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to
      estimate the global epidemiology of central nervous system vascular lesions,
      including unruptured and ruptured aneurysms, arteriovenous malformations,
      cavernous malformations, dural arteriovenous fistulas, developmental venous
      anomalies, and vein of Galen malformations. Results were organized by World
      Health Organization regions. After literature review, because of a lack of data
      from particular World Health Organization regions, we determined we could only
      provide an estimate of aSAH. Using data from studies with aSAH and 12 high
      quality stroke studies from regions lacking data, we meta-analyzed the yearly
      crude incidence of aSAH per 100,000 persons. Estimates were generated via random
      effects models. RESULTS: From an initial yield of 1492 studies, 46 manuscripts on
      aSAH incidence were included. The final meta-analysis included 58 studies from 31
      different countries. We estimated the global crude incidence for aSAH to be 6.67
      per 100,000 persons with a wide variation across WHO regions from 0.71 to 12.38
      per 100,000 persons. CONCLUSIONS: Worldwide, almost 500,000 individuals will
      suffer from aSAH each year, with almost two-thirds in low- and middle-income
      countries.

PMID- 29649644
TI  - Endoscopic Transseptal Approach with Bilateral Nasoseptal Flap in Challenging
      Skull-Base Tumors.
AB  - OBJECTIVE: We sought to examine the utility of an endoscopic transseptal approach
      and creation of a bilateral nasoseptal flap using a 2-nostrils/4-hands technique
      in patients with challenging skull-base tumors. METHODS: The medical records of
      patients operated on via an endoscopic transseptal approach between 2009 and 2017
      were retrospectively reviewed. Two patients with ossifying fibroma, 2 with
      orbital hemangioma, 2 with trigeminal nerve schwannoma, and 1 patient each with
      juvenile angiofibroma, meningioma, and myxofibrosarcoma were included in the
      study. The surgical technique and endoscopic anatomy are presented. RESULTS: The
      mean age of the 4 male and 5 female patients was 39.9 +/- 14.8 years. By using
      this technique, all 7 tumors were resected with minimal nasal morbidity after a
      mean follow-up of 15.2 +/- 9.4 months. CONCLUSIONS: The endoscopic transseptal
      approach, by creation of a bilateral nasoseptal flap using a 2-nostrils/4-hands
      technique, improves surgical visualization and increases instrument
      maneuverability. Surgical access to challenging skull-base tumors is therefore
      afforded. The procedure also reduces nasal morbidity by preserving the lacrimal
      apparatus and anterior maxilla structures and avoiding septal perforation and
      traumatic nose traction.

PMID- 29649645
TI  - Giant Pseudoaneurysm from Superficial Temporal Artery After Trauma.
AB  - An 83-year-old woman presented with a lump on her left frontal region. One month
      ago, she fell and hit the ground with the left side of her head. However, she had
      no evidence of injury. After 10 days, a progressive, painless lump appeared where
      her head was injured. The lump was pulsatile, but it not obviously shrank subtly
      in size with compression of her left superficial temporal artery. The ultrasound
      examination in local hospital demonstrated a pseudoaneurysm. Head computed
      tomography showed an isodense subcutaneous lesion in her left frontal area.
      Further 3-dimensional reconstruction of contrast-enhanced computed tomography
      indicated an aneurysm from her left superficial temporal artery. The aneurysm was
      completely removed by surgery, and pathologic examination confirmed
      pseudoaneurysm. Because the pseudoaneurysm was large, the disadvantage of the
      endovascular treatment options could be a permanent lump. Our patient received a
      surgical resection without facial nerve damage.

PMID- 29649646
TI  - Simultaneous Treatment of Epilepsy and Secondary Dystonia After Anterior Temporal
      Lobectomy and Amygdalohippocampectomy.
AB  - BACKGROUND: The relationship between temporal lobe epilepsy and focal limb
      dystonia is a well-recognized phenomenon, yet its pathogenesis and anatomic
      foundation are not well understood. Here, we describe 2 patients with refractory
      focal epilepsy and contralateral focal limb dystonia whose seizures and dystonic
      symptoms simultaneously resolved after anterior temporal lobectomy and
      amygdalohippocampectomy. CASE DESCRIPTION: We identified 2 patients within the
      Mount Sinai Health system with improvement in dystonia after medial temporal
      lobectomy. Retrospective chart reviews for the clinical history were performed.
      Patient 1 suffered a traumatic injury of the right temporal lobe, developing left
      hemidystonia and epilepsy. He received a right amygdala-hippocampectomy, which
      resolved both. Patient 2 has a history of right temporal glioma resection
      complicated by an infarct, resulting in left hemidystonia and epilepsy. He
      received a right medial temporal resection, which nearly resolved both.
      CONCLUSION: Our cases demonstrate a medial temporal-basal ganglia network
      dysfunction in dystonia-epilepsy that was modulated and cured by resective
      surgery. We hypothesize that the mechanisms behind these observed phenomena were
      due to a pathologic connectivity of the basal ganglia and amygdala-hippocampus.
      To our knowledge, these are the first reported cases of dystonia and concomitant
      epilepsy resolving with temporal lobectomy and provide valuable prognostic
      information for similarly affected patients.

PMID- 29649647
TI  - Clinical Outcomes of Primary and Revision Untethering Surgery in Patients with
      Tethered Cord Syndrome and Spinal Bifida.
AB  - BACKGROUND: Tethered cord syndrome (TCS) is an increasingly recognized clinical
      condition, with untethering surgery considered the classically effective
      treatment. Yet, as evidence has aggregated, the surgical outcomes of untethering
      remain controversial. This study aimed to systematically evaluate the clinical
      outcomes in patients who underwent primary or revision untethering. METHODS: This
      retrospective study was conducted at the Department of Spine Surgery of
      Changzheng Hospital between January and December 2016. Patients with TCS who
      underwent untethering surgery were recruited for the study. Information collected
      included demographic data, main clinical manifestations, and outcomes after
      untethering surgery. RESULTS: A total of 112 patients (60 males and 52 females)
      were included in this study, with mean follow-up of 13.7 years. The surgical
      outcomes of the primary untethering varied among symptoms, with remission rates
      of 30.0% for pain, 24.4% for paresthesia, 18.6% for motor deficit, 12.6% for
      bladder dysfunction, and 21.2% for bowel dysfunction. Moreover, 23.3%-40.2% of
      patients suffered deterioration after surgery during the follow-up period. Twenty
      eight patients underwent revision untethering surgery. In these patients, the
      remission rate decreased by 5.6%-16.7% compared with the primary operation.
      Moreover, most patients (58.8%-70.6%) experienced no benefits after revision
      surgery. CONCLUSIONS: With a possible high risk of recurrence, further
      exploration of the indications and timing of the untethering surgery is needed.
      Conservative treatment and omnidirectional care might be a better choice for
      patients with retethering with recurrent symptoms.

PMID- 29649648
TI  - Ultra-Early Treatment for Poor-Grade Aneurysmal Subarachnoid Hemorrhage: A
      Systematic Review and Meta-Analysis.
AB  - BACKGROUND: It remains unknown if ultra-early (within 24 hours after onset)
      treatment can improve the prognosis in patients with poor-grade aneurysmal
      subarachnoid hemorrhage (aSAH). We aimed to evaluate the effect of ultra-early
      treatment on functional outcomes and mortality in patients with poor-grade aSAH
      via a systematic review and meta-analysis. METHODS: We performed a literature
      search in the PubMed, MEDLINE, and Web of Science databases. Primary outcomes
      were death and functional outcome assessed at any time period. Secondary outcomes
      were the rebleeding rate before an aneurysm occlusion procedure and the incidence
      of intraoperative technique difficulty (ITD). The results are reported as odds
      ratio (OR) with 95% confidence interval (CI). RESULTS: A total of 14 articles
      containing 1111 patients met our inclusion criteria and were included in our
      analysis. The pooled incidence was 47% (95% CI, 40%-54%) for favorable outcome
      across 13 studies, 26% (95% CI, 19%-32%) for mortality in 11 studies, 10% (95%
      CI, 3%-16%) for rebleeding in 5 studies, and 20% (95% CI, 10%-31%) for ITD in 5
      studies after ultra-early treatment of poor-grade aSAH. Compared with delayed
      treatment (>24 hours), the ultra-early treatment failed to improve outcomes (OR,
      1.23; 95% CI, 0.75-2.01; P = 0.40) or reduce mortality (OR, 0.84; 95% CI, 0.58
      1.22; P = 0.45), but tended to prevent preoperative rebleeding (OR, 0.59; 95% CI,
      0.32 to 1.07; P = 0.08) in 6, 4, and 4 case-control studies, respectively.
      CONCLUSIONS: Our findings show no significant change both in functional outcome
      and mortality between ultra-early and delayed treatment although ultra-early
      treatment may be associated with lower rebleeding rate.

PMID- 29649649
TI  - Aberrant Expression of Extracellular Signal-Regulated Kinase and 15
      Hydroxyprostaglandin Dehydrogenase Indicates Radiation Resistance and Poor
      Prognosis for Patients with Clival Chordomas.
AB  - OBJECTIVE: To explore molecular markers of radiosensitivity and prognostic
      factors in patients with clival chordomas. METHODS: Retrospective review was
      performed of 35 patients. Mean follow-up interval was 66.37 months (range, 29-106
      months). Kaplan-Meier method was used for survival analysis. Immunohistochemical
      staining was used to detect expression levels of extracellular signal-regulated
      kinase (ERK) and 15-hydroxyprostaglandin dehydrogenase (HPGD). RESULTS: Total
      resection was achieved in 12 cases, subtotal resection was achieved in 12 cases,
      and partial resection was achieved in 11 cases. Radiation-sensitive group
      comprised 17 cases, and radiation-resistant (RR) group comprised 18 cases. Five
      year progression-free survival (PFS) rates in total resection and nontotal
      resection groups were 46.3% and 10.1%, respectively (P = 0.005). Mean H-scores of
      ERK in radiation-resistant and radiation-sensitive groups were 110.38 and 82.98,
      respectively (P = 0.043). Mean H-scores of HPGD in radiation-resistant and
      radiation-sensitive groups were 178.62 and 203.47, respectively (P = 0.031). Mean
      PFS in low ERK expression group (58.61 months) was significantly longer than mean
      PFS in high ERK expression group (24.94 months) (P = 0.022). Mean PFS in high
      HPGD expression group (39.54 months) was significantly longer than mean PFS in
      low HPGD expression group (9.5 months) (P = 0.013). CONCLUSIONS: Radical
      resection with protection of important structures is the most effective treatment
      of clival chordomas. High HPGD expression and low ERK expression were associated
      with radiation sensitivity and better prognosis. HPGD and ERK can be used as
      biomarkers to predict prognosis and guide treatment.

PMID- 29649650
TI  - Assessment of Myelopathy in Cervical Ossification of the Posterior Longitudinal
      Ligament by Magnetic Resonance Imaging-Assisted 3-Dimensional Measurement.
AB  - BACKGROUND: Ossification of the posterior longitudinal ligament (OPLL) is a 3
      dimensional (3D) disease that causes cervical myelopathy. The conventional 2
      dimensional (2D) measurement of OPLL has limitations in estimating cord
      compression and myelopathy. In this study, we attempted to use 3D computed
      tomography (CT) and magnetic resonance imaging (MRI) to measure the 3D occupying
      ratio of OPLL and investigate its significance in the assessment of spinal cord
      myelopathy. METHODS: Three-dimensional CT and MRI were performed in 50 patients
      with cervical OPLL at a neutral position before surgery. MRI was done to
      determine the extent of spinal cord compression. The CT data were saved in DICOM
      format and analyzed using Mimics 17.0. Then a 3D model of OPLL was
      semiautomatically segmented at a specific threshold. The following data were
      measured: diameter of the spinal canal, thickness of the OPLL, and 3D volume of
      the OPLL and spinal canal. The Japanese Orthopedic Association (JOA) score was
      used to assess the cervical spinal cord function. RESULTS: Pearson correlation
      analysis showed that both the occupying ratio and the 3D occupying ratio were
      significantly and negatively correlated with the JOA score. Multiple linear
      regression analysis indicated that only the 3D occupying ratio showed a
      significantly negative correlation with the JOA score, whereas age, sex, and the
      occupying ratio were insignificantly associated with the JOA score. CONCLUSIONS:
      The 3D occupying ratio of OPLL is a reliable indicator for assessing the severity
      of spinal cord myelopathy. MRI provides more details about cord compression,
      making the measurement more accurate and objective.

PMID- 29649651
TI  - Internal Maxillary Artery to Middle Cerebral Artery Cranial Bypass: The New "Work
      Horse" for Cerebral Flow Replacement.

PMID- 29649652
TI  - Differentiating aversive conditioning in bistable perception: Avoidance of a
      percept vs. salience of a stimulus.
AB  - Alternating conscious visual perception of bistable stimuli is influenced by
      several factors. In order to understand the effect of negative valence, we tested
      the effect of two types of aversive conditioning on dominance durations in
      binocular rivalry. Participants received either aversive classical conditioning
      of the stimuli shown alone between rivalry blocks, or aversive percept
      conditioning of one of the two possible perceptual choices during rivalry. Both
      groups showed successful aversive conditioning according to skin conductance
      responses and affective valence ratings. However, while classical conditioning
      led to an immediate but short-lived increase in dominance durations of the
      conditioned stimulus, percept conditioning yielded no significant immediate
      effect but tended to decrease durations of the conditioned percept during
      extinction. These results show dissociable effects of value learning on
      perceptual inference in situations of perceptual conflict, depending on whether
      learning relates to the decision between conflicting perceptual choices or the
      sensory stimuli per se.

PMID- 29649653
TI  - A label-free cellulose SERS biosensor chip with improvement of nanoparticle
      enhanced LSPR effects for early diagnosis of subarachnoid hemorrhage-induced
      complications.
AB  - It is very difficult to predict some complications after subarachnoid hemorrhage
      (SAH), despite rapid advances in medical science. Herein, we introduce a label
      free cellulose surface-enhanced Raman spectroscopy (SERS) biosensor chip with pH
      functionalized, gold nanoparticle (AuNP)-enhanced localized surface plasmon
      resonance (LSPR) effects for identification of SAH-induced cerebral vasospasm and
      hydrocephalus caused by cerebrospinal fluid (CSF). The SERS biosensor chip was
      implemented by the synthesis reaction of the AuNPs, which were charged positively
      through pH level adjustment, onto a negatively-charged cellulose substrate with
      xi = -30.7 mV. The zeta potential, nanostructural properties, nanocrystallinity,
      and computational calculation-based electric field distributions of the cellulose
      originated AuNPs were optimized to maximize LSPR phenomena and then
      characterized. Additionally, the performance of the SERS biosensor was compared
      under two representative excitation laser sources in the visible region (532 nm)
      and near-infrared region (785 nm). The Raman activities of our SERS biosensor
      chip were evaluated by trace small molecules (crystal violet, 2 uL), and the
      biosensor achieved an enhancement factor of 3.29 * 109 for the analytic concept
      with an excellent reproducibility of 8.5% relative standard deviation and a
      detection limit of 0.74 pM. Furthermore, the experimental results revealed that
      the five proposed SERS-based biomarkers could provide important information for
      identifying and predicting SAH-induced cerebral vasospasm and hydrocephalus
      complications (91.1% reliability and 19.3% reproducibility). Therefore, this
      facile and effective principle of our SERS biosensor chip may inspire the basis
      and strategies for the development of sensing platforms to predict critical
      complications in various neurosurgical diagnoses.

PMID- 29649654
TI  - HPV DNA methylation at the early promoter and E1/E2 integrity: A comparison
      between HPV16, HPV18 and HPV45 in cervical cancer.
AB  - OBJECTIVES: To compare and describe type-specific characteristics of HPV16, HPV18
      and HPV45 in cervical cancer with respect to 3'LCR methylation and disruption of
      E1/E2. METHODS: The methylation level of 137 cervical cancer samples (70 with
      HPV16, 37 with HPV18, and 30 with HPV45) of Brazilian patients was analyzed by
      pyrosequencing. PCR amplifications were performed to characterize E1 and E2
      disruption as an episomal surrogate. RESULTS: The 3'LCR of HPV16 showed a higher
      methylation at all CpG sites (7%, 9%, 11%, 10% and 10%) than homologous HPV18
      regions (4%, 5%. 6%, 9% and 5%) and HPV45 regions (7%, 7% and 5%). Presence of
      intact E1/E2 was associated with higher HPV16 and HPV18 methylation levels at all
      CpG sites (p < 0.05). Disruption of E1/E2 was more frequently found in HPV45
      (97%) and HPV18 (84%) than in HPV16 DNA (30%). HPV16 disruption was more
      frequently found in E1 (48%) unlike HPV18, where it was found in E2 (61%).
      Concomitant disruption of E1/E2 was most frequent in HPV45 (72%). CONCLUSIONS:
      The findings showed a higher methylation associated with intact E1/E2 for HPV16
      and HPV18. The closely phylogenetic related HPV18 and HPV45 share a similar
      methylation level and the frequency of viral genome disruption.

PMID- 29649655
TI  - Bone mineral density changes over time in diffuse idiopathic skeletal
      hyperostosis of the thoracic spine.
AB  - Diffuse idiopathic skeletal hyperostosis (DISH) is an increasingly prevalent
      ankylosing condition. Patients with DISH have an increased risk of spinal
      fractures, hypothetically the result of biomechanical changes in the spine. The
      aim of this study was to analyze the occurrence of biomechanical stress shielding
      in patients with DISH. To do this, bone mineral density (BMD) was measured
      longitudinally in the vertebral bodies of subjects with and without DISH and in
      the newly formed bone of subjects with DISH. The presence of DISH was evaluated
      using Resnick criteria on two chest computed tomography (CT) scans taken at least
      2.5 years apart from subjects over 50 years of age. Three groups were identified:
      pre-DISH (individuals who developed DISH after the first CT scan), definite DISH
      (individuals who had DISH on both CT scans), and controls (individuals with no
      DISH). Hounsfield units (HU) were measured in the newly formed bone and in
      predefined anterior and posterior portions of the involved vertebral bodies. Mean
      BMD of the newly formed bone increased significantly (mean DeltaHU 137.5; p <
      0.01) during a mean interval of 5 years in the cranial, middle, and caudally
      involved vertebral segments of both DISH groups. Mean BMD of the vertebral bodies
      in the ankylotic segments in the DISH groups did not significantly differ from
      that of the non-ankylotic vertebral bodies of the same subject. In contrast to
      our hypothesis, the HU value of the vertebral body decreased more in the control
      group than in the DISH groups; however, statistical significance was only reached
      at the cranial level in the anterior part of the vertebral body (p = 0.048). Our
      data suggest that 1) vertebral BMD is not influenced by the presence of DISH and
      2) increased spinal stiffness may play a more important role than vertebral BMD
      in the increased fracture risk of and the typical fracture patterns observed in
      individuals with DISH.

PMID- 29649656
TI  - Influence of severe plastic deformation on fatigue life applied by ultrasonic
      peening in welded pipe 316 Stainless Steel joints in corrosive environment.
AB  - Corrosive solutions have an enormous effect on fatigue life of components in
      refinery industry. Several post-processing solutions are proposed to improve the
      weld zone, which is affected by the corrosive solutions. Ultrasonic peening (UP)
      is developed to enhance the fatigue life, specifically in corrosive environments
      and corrosion resistance of the components. The enhancement mechanism of UP is
      based on severe plastic deformation and reduction of tensile residual stress in
      weld toe. In this research, the fatigue-corrosion life of welded 316 Stainless
      Steel (SS) pipe is enhanced through utilizing UP process with different diameters
      of strikers. Fatigue-corrosion life of the weld on 316 SS and 347 SS fillers, as
      experimental samples, is studied in corrosive environments. This study intends to
      shed more light on the influence of corrosion and strength in fatigue-corrosion
      life of the sample materials. Therefore, this article studies the microstructure
      and pitting corrosion of the samples at different zones. The experimental results
      showed enhancement of fatigue-corrosion life after applying UP. The results
      revealed that welding by using 316 SS filler and UP with striker diameter of 4 mm
      have the highest fatigue life in the simulated H2S corrosive environment.

PMID- 29649657
TI  - Contribution of computational model for assessment of heart tissue local stress
      caused by suture in LVAD implantation.
AB  - STUDY: Implantation of a Left Ventricular Assist Device (LVAD) may produce both
      excessive local tissue stress and resulting strain-induced tissue rupture that
      are potential iatrogenic factors influencing the success of the surgical
      attachment of the LVAD into the myocardium. By using a computational simulation
      compared to mechanical tests, we sought to investigate the characteristics of
      stress-induced suture material on porcine myocardium. METHODS: Tensile strength
      experiments (n = 8) were performed on bulk left myocardium to establish a
      hyperelastic reduced polynomial constitutive law. Simultaneously, suture strength
      tests on left myocardium (n = 6) were performed with a standard tensile test
      setup. Experiments were made on bulk ventricular wall with a single U-suture
      (polypropylene 3-0) and a PTFE pledget. Then, a Finite Element simulation of a
      LVAD suture case was performed. Strength versus displacement behavior was
      compared between mechanical and numerical experiments. Local stress fields in the
      model were thus analyzed. RESULTS: A strong correlation between the experimental
      and the numerical responses was observed, validating the relevance of the
      numerical model. A secure damage limit of 100 kPa on heart tissue was defined
      from mechanical suture testing and used to describe numerical results. The impact
      of suture on heart tissue could be accurately determined through new parameters
      of numerical data (stress diffusion, triaxiality stress). Finally, an ideal
      spacing between sutures of 2 mm was proposed. CONCLUSION: Our computational model
      showed a reliable ability to provide and predict various local tissue stresses
      created by suture penetration into the myocardium. In addition, this model
      contributed to providing valuable information useful to design less traumatic
      sutures for LVAD implantation. Therefore, our computational model is a promising
      tool to predict and optimize LVAD myocardial suture.

PMID- 29649658
TI  - Gentamicin-loaded ceramic-biopolymer dual layer coatings on the Ti with improved
      bioactive and corrosion resistance properties for orthopedic applications.
AB  - In orthopedic surgery, osteomyelitis (bone infection) is one of the most serious
      complications in the last few decades and the resident drug delivery is the key
      strategy to overcome this issue. Combination of bioactive materials with
      antibiotics is broadly developed for the handling of osteomyelitis which plays a
      dual role as bone cell growth and as local drug delivery systems for antibiotic
      delivery. TiO2-SiO2 mixtures were fabricated on Ti alloy by anodization method.
      Chitosan-Lysine (CS-LY) biopolymers were coated on composites by
      electrodeposition method and followed by gentamicin sulfate (GS) which was loaded
      as a model drug. The layers were characterized by AT-FTIR, XRD, FE-SEM and EDX
      methods. The mechanical, anticorrosion, antimicrobial effects and
      biocompatibility of the glazes were considered. In addition, drug loading,
      continued and prolonged liberation behaviors of GS from the fabricated coating
      were studied. The apatite development ability and cell viability are outstanding
      for CS-LY-3 coated composites. In vitro cell experimentations indicate that
      osteoblasts show good adhesion and high growth rates for CS-LY-3 coated TiO2-SiO2
      composite substrate. In conclusion, the surface modification of TiO2-SiO2/CS-LY-3
      coated Ti alloy could be used as a carrier for GS, not only to eradicate the
      osteomyelitis caused by Gram-negative and Gram-positive bacteria, but also to
      repair the bone defect initiated by the infection owing to the tunable
      nanocomposite degradation.

PMID- 29649659
TI  - Co-Mn layered double hydroxide as an effective heterogeneous catalyst for
      degradation of organic dyes by activation of peroxymonosulfate.
AB  - In this study, Co-Mn layered double hydroxide (Co-Mn LDH) was synthesized,
      characterized, and tested as heterogeneous catalyst to activate peroxymonosulfate
      (PMS) for degradation of organic dyes. The results of characterization showed
      that Co-Mn LDH had high purity, uniform morphology and large specific surface
      area (49.9379 m2/g). The degradation experiments demonstrated that five different
      dyes with the concentration of 50 mg/L could be decomposed completely within 240
      s using only 0.025 g/L of Co-Mn LDH and 0.1 g/L of PMS. Moreover, Co-Mn LDH/PMS
      system presented the highest decomposition efficiency for acid orange G (AOG)
      compared with other related materials under the same condition. Further
      investigation found that Co-Mn LDH/PMS system had an excellent adaptability in a
      wide pH range (from 3 to 10), and the best efficiency was achieved when the
      solution was natural (pH = 6.87). The mineralization of AOG was assessed by Total
      Organic Carbon (TOC), and 52.2% of TOC was removed. Meanwhile, the good
      reusability and high stability of Co-Mn LDH were demonstrated by recycle tests
      and ion-leaching tests. The catalytic mechanism was explored through quenching
      tests as well as X-ray photoelectron spectroscopy (XPS) analysis. Finally, all of
      the results suggested that Co-Mn LDH/PMS system with high stability and
      decomposition efficiency was suitable for the remediation of organic dyes in
      wastewater.

PMID- 29649660
TI  - Effect of temperature and dispersant (COREXIT(r) EC 9500A) on aerobic
      biodegradation of benzene in a coastal salt marsh sediment.
AB  - The coastal ecosystem in the northern Gulf of Mexico (GoM) has been seriously
      impacted by the 2010 BP oil spill. Two experiments were conducted to study the
      effect of temperature and addition of the dispersant on biodegradation of
      benzene, as a representative of petroleum hydrocarbon, in a coastal salt marsh
      sediment under aerobic conditions. The results show that benzene biodegradation
      was approximately 6 time faster under aerobic conditions (Eh > +300 mV) than
      under anaerobic iron-reduction conditions (+14 mV < Eh < +162 mV). Benzene
      biodegradation in response to temperature was in an order of 20  degrees C > 10 
      degrees C > 30  degrees C as expected in a saline environment. Application of the
      dispersant caused initial fluctuations of benzene vapor pressure during the
      incubation due to its hydrophobic and hydrophilic nature of the molecules.
      Presence of the dispersant shows an inhibitory effect on benzene biodegradation,
      and the inhibition increased with concentration of the dispersant. The Gulf coast
      sediment seems in a favorable scenario to recover from the BP oil spill with an
      average temperature around 20  degrees C in spring and fall season. Application
      of the dispersant may be necessary for the oil spill rescue operation, but its
      side effects may deserve further investigations.

PMID- 29649661
TI  - Risk ranking of environmental contaminants in Xiaoqing River, a heavily polluted
      river along urbanizing Bohai Rim.
AB  - Xiaoqing River, located in the Laizhou Bay of Bohai Sea, is heavily polluted by
      various pollutants including heavy metals, polycyclic aromatic hydrocarbons
      (PAHs), hexachlorocyclohexanes (HCHs), perfluoroalkyl acids (PFAAs), bisphenol A
      (BPA) and pharmaceutical and personal care products (PPCPs). The aim of this
      study is to identify the relative risks of such contaminants that currently
      affect the coastal ecosystem. The median and highest concentrations of PFAAs and
      perfluorooctanoic acid (PFOA) were 3.23 MUg L-1 and 325.28 MUg L-1, and 0.173 MUg
      L-1 and 276.24 MUg L-1, respectively, which were ranked higher when compared with
      global level concentrations. To assess the relative risk levels of
      perfluorooctane sulfonic acid (PFOS), PFOA, and other contaminants in the
      upstream and downstream of the Xiaoqing River and in its tributary, a risk
      ranking analysis was carried out. Copper (Cu), Zinc (Zn), and arsenic (As) showed
      the highest risk values in the Xiaoqing River, while the relative risks of PFOA
      and PFOS differed across the various segments. The risk ranking of PFOA was the
      second highest in the tributary and the fourth highest in the downstream portion
      of the river, whereas the PFOS was found to be the lowest in all the segments.
      Heavy metals and PFOA are the main chemicals that should be controlled in the
      Xiaoqing River. The results of the present study provide a better understanding
      of the potential ecological risks of the contaminants in Xiaoqing River.

PMID- 29649662
TI  - Autophagy attenuates copper-induced mitochondrial dysfunction by regulating
      oxidative stress in chicken hepatocytes.
AB  - Copper (Cu) is an essential trace element that is required for the catalysis of
      several cellular enzymes. Excessive Cu could induce hepatotoxicity in humans and
      multiple animals. The purpose of this study was to investigate the effects of
      autophagy machinery on Cu-induced hepatotoxicity. Chicken hepatocytes were
      cultured in medium in the absence and presence of Cu sulfate (CuSO4) (0, 10, 50,
      and 100 MUM) for 0, 6, 12, and 24 h, and in the combination of CuSO4 and N-acetyl
      l-cysteine (NAC) (1 mM), rapamycin (10 nM), and 3-methyladenine (3-MA) (5 mM) for
      24 h. Results showed that Cu could markedly increase the number of autophagosomes
      and LC3 puncta, induce autophagy-related genes (Beclin1, ATG5, LC3I, LC3II, mTOR,
      and Dynein) mRNA expression and proteins (BECN1, LC3II/LC3I) expression. NAC
      could relieve Cu-induced the changes of above genes and proteins. Additionally,
      rapamycin attenuated Cu-induced the increased lactic dehydrogenase (LDH),
      aspartate amino transferase (AST), and alanine aminotransferase (ALT) activities,
      and SOD-1 mRNA expression as well as the decreased cell viability, reactive
      oxygen species (ROS), hydrogen peroxide, total superoxide dismutase (T-SOD),
      malonaldehyde (MDA), catalase (CAT), HO-1 mRNA expression, adenosine triphosphate
      (ATP) levels, mitochondrial mass, and mitochondria membrane potential (MMP). But
      3-MA had the opposite effects on above factors. Collectively, these findings
      provide strong evidence that Cu could induce autophagy by generating excessive
      ROS in hepatocytes, and autophagy might attenuate Cu-induced mitochondrial
      dysfunction by regulating oxidative stress.

PMID- 29649663
TI  - Binary mixtures of alcohol ethoxylates, nonylphenol ethoxylates and pesticides
      exhibit comparative bioactivity against three pests and toxicological risks to
      aquatic organisms.
AB  - Nonylphenol ethoxylates are widely used surfactants in the industry and
      agriculture. However, seeking for alternatives has been imperative considering
      their effects of the hormonal and other toxicological risks. In the current
      study, the synergistic effects of nonylphenol ethoxylates or alcohol ethoxylates
      on the bioactivity of indoxacarb and acetamiprid were compared. Results showed
      that synergistic ratios of nonylphenol ethoxylates (TX-7~TX-30) and alcohol
      ethoxylates (MOA-5~MOA-20) against Spodoptera exigua, Agrotis ipsilon and Aphis
      citricola decreased with the EO (ethylene oxide) numbers, although different
      magnitudes of decreases were observed. Single toxicities of all ethoxylates to
      Daphnia magna and Brachydanio rerio also dramatically decreased with the EO
      numbers. In terms of joint toxicity, the combined effects of all ethoxylates and
      pesticides upon D. magna turned from synergism to antagonism with the increasing
      EO numbers; the combined effects of nonylphenol ethoxylates and pesticides turned
      from synergism to antagonism with the increasing EO numbers of ethoxylates,
      whereas alcohol ethoxylates and pesticides always showed antagonistic effects
      whatever EO numbers. Overall, alcohol ethoxylates may be potential alternatives
      for nonylphenol ethoxylates as they exhibited nearly comparative bioactivity
      against tested pests and toxicities to D. magna and B. rerio.

PMID- 29649664
TI  - Autophagic-related cell death of Trypanosoma brucei induced by bacteriocin AS-48.
AB  - The parasitic protozoan Trypanosoma brucei is the causative agent of human
      African trypanosomiasis (sleeping sickness) and nagana. Current drug therapies
      have limited efficacy, high toxicity and/or are continually hampered by the
      appearance of resistance. Antimicrobial peptides have recently attracted
      attention as potential parasiticidal compounds. Here, we explore circular
      bacteriocin AS-48's ability to kill clinically relevant bloodstream forms of T.
      brucei gambiense, T. brucei rhodesiense and T. brucei brucei. AS-48 exhibited
      excellent anti-trypanosomal activity in vitro (EC50 = 1-3 nM) against the three
      T. brucei subspecies, but it was innocuous to human cells at 104-fold higher
      concentrations. In contrast to its antibacterial action, AS-48 does not kill the
      parasite through plasma membrane permeabilization but by targeting intracellular
      compartments. This was evidenced by the fact that vital dye internalization
      prohibiting concentrations of AS-48 could kill the parasite at 37  degrees C but
      not at 4  degrees C. Furthermore, AS-48 interacted with the surface of the
      parasite, at least in part via VSG, its uptake was temperature-dependent and
      clathrin-depleted cells were less permissive to the action of AS-48. The
      bacteriocin also caused the appearance of myelin-like structures and double
      membrane autophagic vacuoles. These changes in the parasite's ultrastructure were
      confirmed by fluorescence microscopy as AS-48 induced the production of EGFP
      ATG8.2-labeled autophagosomes. Collectively, these results indicate AS-48 kills
      the parasite through a mechanism involving clathrin-mediated endocytosis of VSG
      bound AS-48 and the induction of autophagic-like cell death. As AS-48 has greater
      in vitro activity than the drugs currently used to treat T. brucei infection and
      does not present any signs of toxicity in mammalian cells, it could be an
      attractive lead compound for the treatment of sleeping sickness and nagana.

PMID- 29649666
TI  - A retrospective study: Does cigarette smoking induce cervical disc degeneration?
AB  - OBJECTIVE: To investigate cigarette smoking's relevance with cervical disc
      degeneration. METHODS: We randomly selected 320 patients who came to our spine
      disease department outpatient clinic with chief complaint of neck-shoulder pain
      during June 2014-June 2016. According to the detailed smoking history, these
      patients were divided into 3 different groups, which were active smoker group
      (AS), passive smoking group (PS) and never-smoker group (NS). Each patient's
      Miyazaki's magnetic resonance imaging (MRI) classification of cervical disc
      degeneration was analyzed based on their cervical MRI films. In addition, VAS
      scores were applied to evaluate the degree of patients' neck-shoulder pain. With
      the help of statistical techniques, relevance between cigarette smoking, cervical
      disc degeneration and neck-shoulder pain were analyzed. RESULTS: In the NS group,
      the overall Miyazaki score, especially for C2/3, C3/4, C5,6 segments, are
      superior to those in the PS group, in addition, the Miyazaki scores for C1/2 -
      C6/7 segments in NS group beat the same segments in AS group with statistical
      significance (P < 0.05). In the AS and PS group, discs from C4/5 to C5/6 segments
      which score IV and V on Miyazaki classification account for a larger proportion
      than those discs from C1/2 to C3/4 segments with statistical significance (P <
      0.05). In the AS group, male cases have larger proportion of Miyazaki level IV
      and V discs than female with statistical significance (P < 0.05). While in the AS
      and PS group, Miyazaki scores of patients whose smoking history ranges from 5 to
      10 years are superior to those with smoking history longer than 10 years, with
      statistical significance (P < 0.05). In addition, VAS scores also vary among the
      three groups, in which, VAS scores in AS group are higher than those in the NS
      group. CONCLUSION: Smoking could accelerate the process of cervical disc
      degeneration, presenting with more severe neck-shoulder pain on the patients. In
      addition, the impact of smoking on the lower cervical discs is greater than the
      upper cervical discs.

PMID- 29649665
TI  - The anti-fecundity effect of 5-azacytidine (5-AzaC) on Schistosoma mansoni is
      linked to dis-regulated transcription, translation and stem cell activities.
AB  - Uncontrolled host immunological reactions directed against tissue-trapped eggs
      precipitate a potentially lethal, pathological cascade responsible for
      schistosomiasis. Blocking schistosome egg production, therefore, presents a
      strategy for simultaneously reducing immunopathology as well as limiting disease
      transmission in endemic or emerging areas. We recently demonstrated that the
      ribonucleoside analogue 5-azacytidine (5-AzaC) inhibited Schistosoma mansoni
      oviposition, egg maturation and ovarian development. While these anti-fecundity
      effects were associated with a loss of DNA methylation, other molecular processes
      affected by 5-AzaC were not examined at the time. By comparing the transcriptomes
      of 5-AzaC-treated females to controls, we provide evidence that this
      ribonucleoside analogue also modulates other crucial aspects of schistosome egg
      laying biology. For example, S. mansoni gene products associated with amino acid
      , carbohydrate-, fatty acid-, nucleotide- and tricarboxylic acid (TCA)-
      homeostasis are all dysregulated in 5-AzaC treated females. To validate the
      metabolic pathway most significantly affected by 5-AzaC, amino acid metabolism,
      nascent protein synthesis was subsequently quantified in adult schistosomes.
      Here, 5-AzaC inhibited this process by 68% +/-16.7% (SEM) in male- and 81% +/
      4.8% (SEM) in female-schistosomes. Furthermore, the transcriptome data indicated
      that adult female stem cells were also affected by 5-AzaC. For instance, 40% of
      transcripts associated with proliferating schistosome cells were significantly
      down-regulated by 5-AzaC. This finding correlated with a considerable reduction
      (95%) in the number of 5-ethynyl-2'-deoxyuridine (EdU) positive cells found in 5
      AzaC-treated females. In addition to protein coding genes, the effect that 5-AzaC
      had on repetitive element expression was also assessed. Here, 46 repeats were
      found differentially transcribed between 5-AzaC-treated and control females with
      long terminal repeat (LTR) and DNA transposon classes being amongst the most
      significant. This study demonstrates that the anti-fecundity activity of 5-AzaC
      affects more than just DNA methylation in schistosome parasites. Further
      characterisation of these processes may reveal novel targets for schistosomiasis
      control.

PMID- 29649667
TI  - Wound healing in anal surgery.

PMID- 29649668
TI  - Laparoscopic vs open restorative proctocolectomy with IPAA for ulcerative
      colitis: Impact of surgical technique on creating a well functioning pouch.
AB  - BACKGROUND: Patients with ulcerative colitis are often young, and proctocolectomy
      with restorative ileo-pouch anal anastomosis is a crucial act that can improve or
      worsen the quality of the rest of their lives. The literature is scant on long
      term functional outcomes after laparoscopy. The purpose of this study was to
      investigate results in terms of pouch function after standardized total
      laparoscopic technique compared with open intervention. MATERIALS AND METHODS:
      This was a retrospective comparative study. Cases were collected from the
      prospectively-maintained database of the Unit of General and Oncologic Surgery,
      XXX, Torino, Italy. Patients treated between May 2005 and May 2015 with three
      stage laparoscopic or open proctocolectomy and ileo-pouch anal anastomosis were
      enrolled. The primary study endpoint was the percentage of well-functioning
      pouches. Secondary endpoints were postoperative early and late outcomes such as
      morbidity and pouch survival. RESULTS: Of the 78 patients identified, 48
      underwent the open technique and 30 underwent laparoscopy. Median follow-up was 4
      years. The overall complication rates were 19% and 13% (p = 0.5), and there were
      major complications (Clavien-Dindo III-IV) in 14.6% and 13.3% of patients in the
      open and laparoscopic groups, respectively (p = 0.8). Late complications occurred
      in 26 patients. Nine (18.8%) and 5 (16.7%) patients had pouchitis (p = 0.8), and
      6 (12.5%) and 2 (6.7%) had cuffitis in the open and laparoscopic groups,
      respectively (p = 0.70). Pouch failure occurred in 2 patients (4.2%) in the open
      group and 2 (6.7%) in the laparoscopic group. The pouch was observed to be
      functioning very well in 18 patients (37.5%) in the open group and in 17 patients
      (56%) in the laparoscopic group (p = 0.09). The study was limited by its
      retrospective, nonrandomized design. CONCLUSION: Our data demonstrated similar
      early and late results after total laparoscopic and open proctocolectomy, in
      particular concerning pouch function.

PMID- 29649670
TI  - The influence of the twin peg design on femoral Interface temperature and maximum
      load to failure in cemented Oxford unicompartmental knee arthroplasty.
AB  - BACKGROUND: The twin peg femoral component was introduced for the cemented Oxford
      unicondylar knee to increase implant stability. The aim of this experimental
      study was to investigate the influence of the twin peg design on femoral
      interface temperature and maximum load to failure in comparison to the single peg
      design. METHODS: In this experimental study medial Oxford unicompartmental knee
      arthroplasty was performed in 12 pairs of fresh-frozen human knees. A cemented
      femoral single peg component was implanted on the one side (group A) and a
      cemented twin peg component on the other side (group B). Cement interface
      temperature was continuously monitored during the procedure. Maximum tensile
      forces of the femoral components were measured by pull-out tests. FINDINGS:
      Maximum femoral interface temperatures did not reach critical values for heat
      necrosis of the bone in group A (mean 28.4, SD 1.2  degrees C) or group B (mean
      27.6, SD 0.5  degrees C). The maximum load to failure was significantly higher in
      the twin peg group (mean 3628.41, SD 650.92 N) compared to the single peg group
      (mean 2979, SD 781 N) (P = 0.016). INTERPRETATION: Our experiments showed higher
      load to failure for the twin peg design compared to the single peg design without
      raising the risk of heat necrosis at the interfacial bone. The twin peg component
      offers a save alternative to the single peg component in a cadaveric setting.

PMID- 29649669
TI  - 360 degrees  virtual reality video for the acquisition of knot tying skills: A
      randomised controlled trial.
AB  - BACKGROUND: 360 degrees  virtual reality (VR) video is an exciting and evolving
      field. Current technology promotes a totally immersive, 3-dimensional (3D), 360
      degrees  experience anywhere in the world using simply a smart phone and virtual
      reality headset. The potential for its application in the field of surgical
      education is enormous. The aim of this study was to determine knot tying skills
      taught with a 360-degree VR video compared to conventional 2D video teaching.
      MATERIAL AND METHODS: This trial was a prospective, randomised controlled study.
      40 foundation year doctors (first year postgraduate) were randomised to either
      the 360-degree VR video (n = 20) or 2D video teaching (n = 20). Participants were
      given 15 min to watch their allocated video. Ability to tie a single handed reef
      knot was then assessed against a marking criteria developed for the Royal College
      of Surgeons, England, (RCSeng) Basic Surgical Skills (BSS) course, by a blinded
      assessor competent in knot tying. Each candidate then underwent further teaching
      using Peyton's four step model. Knot tying technique was then re-assessed.
      RESULTS: Knot tying scores were significantly better in the VR video teaching arm
      when compared with conventional (median knot score 5.0 vs 4.0 p = 0.04). When
      used in combination with face to face skills teaching this difference persisted
      (median knot score 9.5 vs 9.0 p = 0.01). More people in the VR arm constructed a
      complete reef knot than in the 2D arm following face to face teaching (17/20 vs
      12/20). No difference between the groups existed in the time taken to construct a
      reef knot following video and teaching (median time 31.0s vs 30.5s p = 0.89).
      CONCLUSION: This study shows there is significant merit in the application of 360
      degree VR video technology in surgical training, both as an independent teaching
      aid and when used as an adjunct to traditional face to face teaching.

PMID- 29649671
TI  - Trends in resource utilization and prescription of anticonvulsants for patients
      with active epilepsy in Germany from 2003 to 2013 - A ten-year overview.
AB  - This study evaluated trends in resource use and prescription patterns in patients
      with active epilepsy over a 10-year period at the same outpatient clinic of a
      German epilepsy center. We analyzed a cross-sectional patient sample of
      consecutive adults with active epilepsy over a 3-month period in 2013 and
      compared them with equally acquired data from the years 2003 and 2008. Using
      validated patient questionnaires, data on socioeconomic status, course of
      epilepsy, as well as direct and indirect costs were recorded. A total of 198
      patients (mean age: 39.6+/-15.0years, 49.5% male) were enrolled and compared with
      our previous assessments in 2003 (n=101) and 2008 (n=151). In the 2013 cohort,
      75.8% of the patients had focal epilepsy, and the majority were taking
      antiepileptic drugs (AEDs) (39.9% monotherapy, 59.1% polytherapy). We calculated
      epilepsy-specific costs of ?3674 per three months per patient. Direct medical
      costs were mainly due to anticonvulsants (20.9% of total direct costs) and to
      hospitalization (20.8% of total direct costs). The proportion of enzyme-inducing
      anticonvulsants and 'old' AEDs decreased between 2003 and 2013. Indirect costs of
      ?1795 in 2013 were mainly due to early retirement (55.0% of total indirect
      costs), unemployment (26.5%), and days off due to seizures (18.2%). In contrast
      to our previous findings from 2003 and 2008, our data show a stagnating cost
      increase with slightly reduced total costs and balanced direct and indirect costs
      in patients with active epilepsy. These findings are accompanied by an ongoing
      cost-neutral increase in the prescription of 'newer' and non-enzyme-inducing
      AEDs. However, the number and distribution of indirect cost components remained
      unchanged.

PMID- 29649673
TI  - The relationship between impulsivity and panic disorder-agoraphobia: The role of
      affective temperament.
AB  - There are opinions regarding that impulsivity may play a role in the pathogenesis
      of neuropsychiatric disorders. The aim of this study was to investigate the
      relationship between impulsivity and panic disorder (PD) in the patient group, to
      compare impulsivity and affective temperamental traits between patients and
      healthy controls and to investigate whether there is a relationship between
      impulsivity and affective temperamental traits. Participants comprised 70
      patients with PD and 58 healthy volunteers. The Panic Agoraphobia Scale (PAS),
      the Barratt Impulsiveness Scale (BIS-11) and the Temperament Evaluation of
      Memphis, Pisa, Paris, San Diego Autoquestionnaire (TEMPS-A) were applied.
      Patients have significantly higher scores in affective temperament (except
      hyperthymic) and attentional impulsiveness subscales than the healthy controls.
      Positive and negative correlations were found between some PAS and BIS-11 scores
      as well as correlations between especially cyclothymic, hyperthymic, irritable
      and anxious subscale scores of the TEMPS-A and the BIS-11 scores in the patient
      group. The results of this study indicate a relationship between impulsivity and
      PD. The correlations found between affective temperament dimensions and
      impulsivity suggest how affective temperamental traits may influence different
      impulsivity dimensions.

PMID- 29649672
TI  - Leading up to saying "yes": A qualitative study on the experience of patients
      with refractory epilepsy regarding presurgical investigation for resective
      surgery.
AB  - OBJECTIVES: Adult patients with refractory epilepsy who are potential candidates
      for resective surgery undergo a period of presurgical investigation in tertiary
      epilepsy centers (TECs), where they engage extensively with healthcare
      professionals and receive a range of treatment-related information. This
      qualitative study aimed to examine the experiences of adult patients with
      refractory epilepsy leading up to and during presurgical investigation and how
      their perceptions of resective surgery are shaped. METHODS: In-depth interviews
      with 12 patients and six epilepsy specialist clinicians and 12 observations of
      routine patient-clinician consultations took place at two TECs in Sydney,
      Australia. Data were thematically analyzed via group work. RESULTS: Patients
      reflected on prior experiences of poor seizure control and inadequate
      antiepileptic drug management and a lack of clarity about their condition before
      referral to tertiary care. Poor continuity of care and disrupted care transitions
      affected patients from regional locations. Tertiary referral increased engagement
      with personalized information about refractory epilepsy, which intensified during
      presurgical assessments with additional hospital visits and consultations.
      Experiential information, such as testimonials of other patients, influenced
      perceptions of surgery and fostered more trust and confidence towards healthcare
      professionals. CONCLUSION: Qualitative inquiry detailed multifaceted effects of
      information on patients' overall treatment trajectory and experience of
      healthcare. Earlier patient identification for surgical assessments should be
      accompanied by access to good quality information at primary and community care
      levels and strengthened referral processes.

PMID- 29649674
TI  - Are there clinical and neurophysiologic predictive factors for a positive
      response to HF-rTMS in patients with treatment-resistant depression?
AB  - Better selection of patients with treatment-resistant depression for high
      frequency repetitive transcranial magnetic stimulation (HF-rTMS) would make the
      procedure more efficient. The objective of this study was to search for clinical
      and neurophysiologic predictors of therapeutic response with a special focus on
      the bipolar population. Forty patients (30 bipolar) underwent 20 daily sessions
      of HF-rTMS. Clinical outcome measures included the 21-item Hamilton Depression
      Rating Scale, the Beck Depression Inventory, the Clinical Global Impression, and
      the Patient Global Impression. Neurophysiologic measurements included repeated
      estimation of the motor threshold and cortical silent period. Improvement was
      obtained in all psychometric scales, with no difference between unipolar and
      bipolar patients. Longer duration of the illness, higher number of prior
      hospitalizations, and more disturbed activity were associated with a worse
      response to rTMS, and somatic anxiety, sleep disorders, and health worries were
      positive predictors. In bipolar patients, longer disease duration and therapy
      with mirtazapine, mianserin, trazodone, hydroxyzine, and promethazine were
      associated with a worse response. Sleep disturbances, higher baseline motor
      threshold, and longer cortical silent period predicted a better response. In this
      study, we found several clinical and neurophysiologic predictors of better/worse
      responses to the standard HF-rTMS protocol. Our preliminary data need to be
      reproduced.

PMID- 29649675
TI  - Establishing a coherent and replicable measurement model of the Edinburgh
      Postnatal Depression Scale.
AB  - The 10-item Edinburgh Postnatal Depression Scale (EPDS) is an established
      screening tool for postnatal depression. Inconsistent findings in factor
      structure and replication difficulties have limited the scope of development of
      the measure as a multi-dimensional tool. The current investigation sought to
      robustly determine the underlying factor structure of the EPDS and the
      replicability and stability of the most plausible model identified. A between
      subjects design was used. EPDS data were collected postpartum from two
      independent cohorts using identical data capture methods. Datasets were examined
      with confirmatory factor analysis, model invariance testing and systematic
      evaluation of relational and internal aspects of the measure. Participants were
      two samples of postpartum women in England assessed at three months (n = 245) and
      six months (n = 217). The findings showed a three-factor seven-item model of the
      EPDS offered an excellent fit to the data, and was observed to be replicable in
      both datasets and invariant as a function of time point of assessment. Some EPDS
      sub-scale scores were significantly higher at six months. The EPDS is multi
      dimensional and a robust measurement model comprises three factors that are
      replicable. The potential utility of the sub-scale components identified requires
      further research to identify a role in contemporary screening practice.

PMID- 29649676
TI  - Intradural spinal tumors: 10 - years surgical experience in a single institution.
AB  - OBJECTIVES: The aim of the study is to present the therapeutic results of
      intradural tumor management over a 10 years period in a single institution.
      PATIENTS AND METHODS: The study consists in a prospective case series of patients
      treated at the neurosurgery service of the Social Security Institute of Mexico
      State and Provinces (ISSSEMYM), between January 2006 and December 2016. All
      patients were provided with information about the procedure and signed informed
      consent and institutional board approved files review for this study. RESULTS:
      Thirty-five patients with intradural tumor were treated between 2006-2016. Most
      frequent lesions were extramedullary (30 patients, 85.7%). Most frequent tumor
      was Schwannoma, with thoracic/thoraco-lumbar location, being the most frequent
      location. All patients underwent surgical treatment, with total gross resection
      accomplished in 19 patients (54.3%). Surgical complication rate was 11.4%. Spine
      instrumentation was necessary in 26 patients (74.3%) because of bone destruction
      by the tumor, or bone removal for approach. All patients with intramedullary
      lesions and 5 patients (16.7%) with extramedullary lesions received post
      operative radiotherapy. During the follow-up, 8.5% of patients had
      recurrence/progression of residual disease. CONCLUSIONS: Microsurgery is the
      treatment of choice for intradural spinal tumors, and gross total resection with
      low morbidity must be the surgical goal. When this is not possible, partial
      resection and adjuvant therapy with radiosurgery are a valid option. Patients
      most be long followed-up because of recurrence risk or disease progression.

PMID- 29649677
TI  - The solvent effects on dimethyl phthalate investigated by FTIR characterization,
      solvent parameter correlation and DFT computation.
AB  - This study set out with the aim of investigating the solvent effects on dimethyl
      phthalate (DMP) using FTIR characterization, solvent parameter correlation and
      DFT calculation. DMP exposed to 17 organic solvents manifested varying shift in
      the carbonyl stretching vibration frequency (nuCO). Non-alkanols induced Band I
      and alkanols produced Band I and Band II. Through correlating the nuCO with the
      empirical solvent scales including acceptor parameter (AN), Schleyer's linear
      free energy parameter (G), and linear free salvation energy relationships (LSER),
      Band I was mainly ascribed to non-specific effects from either non-alkanols or
      alkanol polymers ((alkanol)n). nuCO of the latter indicated minor red shift and
      less variability compared to the former. An assumption was made and validated
      about the sequestering of hydroxyl group by the bulky hydrophobic chain in
      (alkanol)n, creating what we refer to as "screening effects". Ab initio
      calculation, on the other hand, provided insights for possible hydrogen binding
      between DMP and (ethanol)n or between ethanol monomers. The two components of
      Band I observed in inert solvents were assigned to the two CO groups adopting
      differentiated conformations. This in turn prompted our consideration that
      hydrogen binding was highly selective in favor of lowly associated (alkanol)n and
      the particular CO group having relatively less steric hindrance and stronger
      electron-donating capacity. Band II was therefore believed to derive from
      hydrogen-bond interactions mainly in manner of 1:1 and 1:2 DMP-(alkanol)n
      complexes.

PMID- 29649678
TI  - Spectrophotometric, colorimetric and visually detection of Pseudomonas aeruginosa
      ETA gene based gold nanoparticles DNA probe and endonuclease enzyme.
AB  - Colorimetric DNA detection is preferred over other methods for clinical molecular
      diagnosis because it does not require expensive equipment. In the present study,
      the colorimetric method based on gold nanoparticles (GNPs) and endonuclease
      enzyme was used for the detection of P. aeruginosa ETA gene. Firstly, the primers
      and probe for P. aeruginosa exotoxin A (ETA) gene were designed and checked for
      specificity by the PCR method. Then, GNPs were synthesized using the citrate
      reduction method and conjugated with the prepared probe to develop the new nano
      biosensor. Next, the extracted target DNA of the bacteria was added to GNP-probe
      complex to check its efficacy for P. aeruginosa ETA gene diagnosis. A decrease in
      absorbance was seen when GNP-probe-target DNA cleaved into the small fragments of
      BamHI endonuclease due to the weakened electrostatic interaction between GNPs and
      the shortened DNA. The right shift of the absorbance peak from 530 to 562nm
      occurred after adding the endonuclease. It was measured using a UV-VIS absorption
      spectroscopy that indicates the existence of the P. aeruginosa ETA gene.
      Sensitivity was determined in the presence of different concentrations of target
      DNA of P. aeruginosa. The results obtained from the optimized conditions showed
      that the absorbance value has linear correlation with concentration of target DNA
      (R: 0.9850) in the range of 10-50ngmL-1 with the limit detection of 9.899ngmL-1.
      Thus, the specificity of the new method for detection of P. aeruginosa was
      established in comparison with other bacteria. Additionally, the designed assay
      was quantitatively applied to detect the P. aeruginosa ETA gene from 103 to
      108CFUmL-1 in real samples with a detection limit of 320CFUmL-1.

PMID- 29649679
TI  - Applicability of samarium(III) complexes for the role of luminescent molecular
      sensors for monitoring progress of photopolymerization processes and control of
      the thickness of polymer coatings.
AB  - Applicability of 15 trivalent samarium complexes as novel luminescent probes for
      monitoring progress of photopolymerization processes or thickness of polymer
      coatings by the Fluorescence Probe Technique (FPT) was studied. Three groups of
      samarium(III) complexes were evaluated in cationic photopolymerization of
      triethylene glycol divinyl ether monomer (TEGDVE) and free-radical
      photopolymerization of trimethylolpropane triacrylate (TMPTA). The complexes were
      the derivatives of tris(4,4,4-trifluoro-1-(2-thienyl)-1,3
      butanedionate)samarium(III), tris(4,4,4-trifluoro-1-phenyl-1,3
      butanedionate)samarium(III) and tris(4,4,4-trifluoro-1-(2-naphthyl)-1,3
      butanedionate)samarium(III), which were further coordinated with auxiliary
      ligands, such as 1,10-phenanthroline, triphenylphosphine oxide, tributylphosphine
      oxide and trioctylphosphine oxide. It has been found that most of the complexes
      studied are sensitive enough to be used as luminescent probes for monitoring
      progress of cationic photopolymerization of vinyl ether monomers over entire
      range of monomer conversions. In the case of free-radical polymerization
      processes, the samarium(III) complexes are not sensitive enough to changes of
      microviscosity and/or micropolarity of the medium, so they cannot be used to
      monitor progress of the polymerization. However, high stability of luminescence
      intensity of some of these complexes under free-radical polymerization conditions
      makes them good candidates for application as thickness sensors for polymer
      coatings prepared by free-radical photopolymerization. A quantitative
      relationship between a coating thickness and the luminescence intensity of the
      samarium(III) probes has been derived and verified experimentally within a broad
      range of the thicknesses.

PMID- 29649680
TI  - Development of a carbazole-based fluorescence probe for G-quadruplex DNA: The
      importance of side-group effect on binding specificity.
AB  - G-quadruplex DNAs are highly prevalent in the human genome and involved in many
      important biological processes. However, many aspects of their biological
      mechanism and significance still need to be elucidated. Therefore, the
      development of fluorescent probes for G-quadruplex detection is important for the
      basic research. We report here on the development of small molecular dyes
      designed on the basis of carbazole scaffold by introducing styrene-like
      substituents at its 9-position, for the purpose of G-quadruplex recognition.
      Results revealed that the side group on the carbazole scaffold was very important
      for their ability to selectively recognize G-quadruplex DNA structures. 1a with
      the pyridine side group displayed excellent fluorescence signal turn-on property
      for the specific discrimination of G-quadruplex DNAs against other nucleic acids.
      The characteristics of 1a were further investigated with UV-vis
      spectrophotometry, fluorescence, circular dichroism, FID assay and molecular
      docking to validate the selectivity, sensitivity and detailed binding mode toward
      G-quadruplex DNAs.

PMID- 29649681
TI  - Forensic parameters for 15 autosomal STRs in Mestizo population from the state of
      Guerrero (South, Mexico).
AB  - Allele distribution and forensic parameters were estimated for 15 STR loci
      (AmpFlSTR Identifiler kit) in 251 Mexican-Mestizos from the state of Guerrero
      (South, Mexico). Genotype distribution was in agreement with Hardy-Weinberg
      expectations for all 15 STRs. Similarly, linkage disequilibrium test demonstrated
      no association between pair of loci. The power of exclusion and power of
      discrimination values were 99.999634444% and >99.99999999%, respectively. Genetic
      relationship analysis regarding Mestizo populations from the main geographic
      regions of Mexico suggests that the Center and the present South regions conform
      one population cluster, separated from the Southeast and Northwest regions.

PMID- 29649682
TI  - A giant virus infecting green algae encodes key fermentation genes.
AB  - The family Mimiviridae contains uncommonly large viruses, many of which were
      isolated using a free-living amoeba as a host. Although the genomes of these and
      other mimivirids that infect marine heterokont and haptophyte protists have now
      been sequenced, there has yet to be a genomic investigation of a mimivirid that
      infects a member of the Viridiplantae lineage (green algae and land plants). Here
      we characterize the 668-kilobase complete genome of TetV-1, a mimivirid that
      infects the cosmopolitan green alga Tetraselmis (Chlorodendrophyceae). The
      analysis revealed genes not previously seen in viruses, such as the mannitol
      metabolism enzyme mannitol 1-phosphate dehydrogenase, the saccharide degradation
      enzyme alpha-galactosidase, and the key fermentation genes pyruvate formate-lyase
      and pyruvate formate-lyase activating enzyme. The TetV genome is the largest
      sequenced to date for a virus that infects a photosynthetic organism, and its
      genes reveal unprecedented mechanisms by which viruses manipulate their host's
      metabolism.

PMID- 29649683
TI  - Modulation of UDP-glucuronidation by acridinone antitumor agents C-1305 and C
      1311 in HepG2 and HT29 cell lines, despite slight impact in noncellular systems.
AB  - BACKGROUND: Among the studied antitumor acridinone derivatives developed in our
      laboratory, 5-dimethylaminopropylamino-8-hydroxytriazoloacridinone (C-1305) and 5
      diethylaminoethylamino-8-hydroxyimidazoacridinone (C-1311) exhibited cytotoxic
      and antitumor properties against several cancer types and were selected to be
      evaluated in preclinical and early-phase clinical trials. In the present work, we
      investigated the impact of C-1305 and C-1311 on UDP-glucuronosyltransferase (UGT)
      activity. METHODS: Enzyme activity modulation was studied using HPLC by analyzing
      standard UGT substrate metabolism in the presence and absence of antitumor drugs.
      The investigations were performed in two model systems: (i) under noncellular
      conditions, including human liver microsomes (HLM) and recombinant UGT1A1, 1A9
      and 1A10 isoenzymes and (ii) in tumor cells. RESULTS: There was observed a slight
      impact of studied drugs on enzyme activity. Only UGT1A1 action was altered by
      both compounds. The modulatory effects of UGT activity in cellular systems
      depended on the tumor cell type. In the case of HepG2, C-1305 and C-1311 strongly
      induced UGT activity, particularly for C-1311, at concentrations significantly
      lower than the EC50. This effect contradicted irinotecan mediated UGT inhibition.
      HT29 colon tumor cells were less sensitive than HepG2 to enzyme modulation in the
      presence of the studied compounds, particularly C-1305, where enzymatic
      inhibition similar to that of irinotecan was observed. CONCLUSIONS: The results
      demonstrated that UGT activity modulation should be expected in the case of
      antitumor therapy with C-1305 or/and C-1311. Analysis of the results indicated
      that these modulations would occur via cellular regulatory pathways not by direct
      drug-enzyme interactions.

PMID- 29649684
TI  - The ROME (Retrospective Observational Multicenter study on Eslicarbazepine)
      study: Efficacy and behavioural effects of Eslicarbazepine acetate as adjunctive
      therapy for adults with partial onset seizures in real life.
AB  - PURPOSE: Eslicarbazepine acetate (ESL) is a third-generation member of the
      dibenzazepine family approved in 2009 by the European Medicines Agency with the
      indication of adjunctive therapy in adult people with partial-onset seizures
      (PPOS). We aimed at assessing the ESL impact on seizure frequency and quality of
      life in PPOS with a particular attention to sleepiness and depression. METHODS:
      We evaluated 50 adult PPOS (>18 years; 48 +/- 14 years-old; 23 males) treated
      with adjunctive ESL for >=2months with a retrospective multi-centric design.
      Clinical files of the last 2 years were reviewed checking for monthly seizure
      frequency, treatment retention rate, adverse drug reactions (ADRs), concomitant
      anti-epileptic drugs and behavioural scales for sleepiness (Stanford Sleepiness
      Scale, SSS, and Epworth Sleepiness Scale, ESS), depression (Beck Depression
      Inventory-II, BDI) and overall quality of life (QOLIE-31). RESULTS: At the end of
      96 +/- 28 days of ESL treatment, the mean seizure reduction was 56%; 60% of
      patients had seizure reduction above 50%, with a 31% of the whole population
      becoming seizure free. We reported 16 ADRs with 4 hyponatremia. Retention rate
      was 76%. Patient reported less sleepiness after ESL (SSS, p = 0.031; ESS, p =
      0.0000002). Before ESL, 38% of patients had pathologic BDI scores, which
      normalized in most of them (73%) after ESL (BDI improvement, p = 0.000012). These
      scores resulted in an amelioration of quality of life (QOLIE-31, p = 0.000002).
      CONCLUSIONS: ESL is a safe and effective anti-epileptic drug in a real life
      scenario, with an excellent behavioural profile for the overall quality of life
      and, in particular, for sleepiness and depression.

PMID- 29649685
TI  - Gross beta determination in drinking water using scintillating fiber array
      detector.
AB  - A scintillating fiber array detector for measuring gross beta counting is
      developed to monitor the real-time radioactivity in drinking water. The detector,
      placed in a stainless-steel tank, consists of 1096 scintillating fibers, both
      sides of which are connected to a photomultiplier tube. The detector parameters,
      including working voltage, background counting rate and stability, are tested,
      and the detection efficiency is calibrated using standard potassium chloride
      solution. Water samples are measured with the detector and the results are
      compared with those by evaporation method. The results show consistency with
      those by evaporation method. The background counting rate of the detector is
      38.131 +/- 0.005 cps, and the detection efficiency for beta particles is 0.37 +/-
      0.01 cps/(Bq/l). The MDAC of this system can be less than 1.0 Bq/l for beta
      particles in 120 min without pre-concentration.

PMID- 29649686
TI  - Optimization design research for 89Sr production in China Experimental Fast
      Reactor.
AB  - As the first sodium cooled fast reactor in China, China Experimental Fast Reactor
      (CEFR) has many characteristics, such as high power rating, high neutron flux and
      high neutron leakage as its hard spectrum. These leakage neutrons can be used to
      produce 89Sr by fast neutrons (n, p) reaction. By means of some special designs,
      including designing optimized target assembly, choosing reasonable irradiation
      location and appropriate irradiation cycle length, in order to improve specific
      activity of 89Sr. The MNCP code was used to the calculations coupled ORIGRN2
      procedure. The higher activity of 89Sr can be obtained by these optimization
      designs, so it is feasible to produce 89Sr in the fuel region of CEFR.

PMID- 29649687
TI  - Whether time of operation does not increase the mortality rate in emergency
      surgery?

PMID- 29649688
TI  - Recombinant outer membrane protein 25c from Brucella abortus induces Th1 and Th2
      mediated protection against Brucella abortus infection in mouse model.
AB  - Development of a safe and efficacious vaccine for brucellosis is a long standing
      challenge for scientists. Recognizing potential antigens towards developing
      vaccine candidate is crucial. Omp25c, a porin protein of Brucella, is a paralog
      of two previously identified promising vaccine candidates namely, Omp25 and
      Omp31, with notable sequence identity. Also, Omp25c is conserved in all major
      Brucella species. This highlights the possibility of employing this protein in
      multivalent subunit vaccine based approach of Brucella management. In this study,
      we were interested in examining the immunogenicity and protective efficacy of
      Omp25c against Brucella infections. Recombinant unlipidated form of this antigen
      (rOmp25c) produced, upon intraperitoneal immunization in BALB/c mice along with
      Freund's adjuvant, was confirmed to be highly immunogenic; leading to high IgG
      antibody titers during the study duration. The IgG2a/IgG2b ratio of anti-rOmp25c
      antibodies revealed elicitation of Th2 based humoral immunity. Lymphocyte
      proliferation study divulged induction of specific memory response and secretion
      of both Th1-type (IFN-gamma, GM-CSF and TNF-alpha) and Th2-type cytokine (IL-5)
      from restimulated splenocytes of rOmp25c immunized mice. CD4 T-cell subpopulation
      was comparatively increased than total B cell subpopulation in case of immunized
      mice, indicating the induction of strong cell-mediated (Th1 biased) immunity than
      humoral (Th2) immunity. The collective Th1 plus Th2 immune response specific to
      rOmp25c could be the reason for protection against Brucella challenge observed in
      mice groups that was comparable with S19 vaccine strain. Thus, the study
      encourages rOmp25c as a potent candidate vaccine against brucellosis.

PMID- 29649689
TI  - High-fat diet alters PAS kinase regulation by fasting and feeding in liver.
AB  - The prevalence of overweight and obesity in the population, along with their
      associated complications, is a major factor contributing to increased morbidity
      and mortality in developed countries. The liver is a vital organ for maintaining
      metabolic homeostasis, especially in the adjustment periods in fasting and
      feeding. Per-Arnt-Sim (PAS) kinase (PASK) controls glucose homeostasis and energy
      metabolism in response to nutritional status. PASK-deficient mice with a high-fat
      diet (HFD) resist the development of obesity and hepatic steatosis, with improved
      insulin sensitivity. We have investigated the regulation of the PASK expression
      in an HFD, as well as its role in adapting to fasting and feeding conditions.
      PASK-deficient mice with an HFD record improved parameters for the following:
      body weight, glucose tolerance, insulin resistance and serum lipid parameters. An
      HFD alters the down-regulation of Pask expression produced by fasting, as
      normally happens in a standard-fat diet. PASK deficiency blocks or diminishes the
      expression of many genes overexpressed in HFD-fed mice, such as the following:
      transcription factors involved in the regulation of gluconeogenic enzymes, the
      transport of fatty acid into mitochondria, beta-oxidation and de novo
      lipogenesis. PASK also regulates gene expression posttranscriptionally through
      the short noncoding RNAs involved in lipid metabolism and glucose homeostasis.
      The expression of miR-33a and miR-143 changes in PASK-deficient mice with an HFD.
      Thus, PASK-deficient mice improved their adaptation to feeding/fasting through a
      highly regulated molecular mechanism that controls the expression and function of
      the transcription factors, enzymes and miRNAs involved in glucose and insulin
      signaling.

PMID- 29649690
TI  - Effects of sludge enhanced aeration on nutrient contents and phytotoxicity of
      anaerobically digested centrate.
AB  - In this study, we investigated the impact of intensive aeration pre-treatment on
      nutrient contents and phytotoxicity of anaerobically digested manure centrate.
      Activated sludge from conventional wastewater treatment plants was added to
      reinforce the aeration process. Results show that the addition of activated
      sludge did not negatively affect the nutrient contents, but significantly reduced
      the phytotoxicity of digested centrate, as indicated by an enhancement of seed
      germination index, during the aeration treatment. Based on the orthogonal
      experiment and following statistical analysis, the lowest phytotoxicity of
      digested centrate could be achieved under the aeration conditions: sludge
      concentration of 6 g/L, aeration time of 2 h, gas/water ratio of 40:1, and pH =
      6.5. Of these operational parameters, the digested centrate pH dominantly
      determined its nutrient contents (e.g., amino acids, total phosphorus, and
      ammonium) and phytotoxicity. These results were further verified by hydroponic
      experiments, which showed that using digested centrate after sludge enhanced
      aeration as the nutrient solution facilitated the growth and dry biomass of
      maize.

PMID- 29649691
TI  - Efficient degradation of atrazine by BiOBr/UiO-66 composite photocatalyst under
      visible light irradiation: Environmental factors, mechanisms and degradation
      pathways.
AB  - Atrazine, a typical herbicide, has caused extensive concern due to its wide
      application and persistance. In this work, a visible light responsive
      photocatalyst BiOBr/UiO-66 was synthesized and applied to the degradation of
      atrazine. The BiOBr/UiO-66 materials exhibited significantly enhanced
      photocatalytic performance on the degradation of atrazine under visible light
      irradiation compared to pure BiOBr. Moreover, the effects of typical environment
      factors (i.e. pH, common anions, inorganic cations and water matrix) on the
      degradation of atrazine were investigated extensively. Results showed that
      atrazine was degraded with the fastest rate at the strong acidity conditions of
      pH = 3.1 in the investigated pH region (3.1-9.4). The photocatalytic degradation
      of atrazine was obviously inhibited by HCO3- and SO42-. However, Cl- had
      negligible influence on the degradation of atrazine. Inorganic cations had little
      influence on the degradation of atrazine. Futhermore, the water matrix showed
      apparent impacts on the photocatalytic degradation of atrazine by BiOBr/UiO-66.
      In mineral water, tap water and river water, the removal efficiency of atrazine
      was evidently lower than that in pure water. The main active species that
      responsible for the degradation of atrazine by BiOBr/UiO-66 were determined to be
      .O2- and h+. Ultimately, the degradation pathways of atrazine were proposed based
      on the intermediates detected by LC-MS/MS.

PMID- 29649692
TI  - Emissions of toxic pollutants from co-combustion of demolition and construction
      wood and household waste fuel blends.
AB  - Four different types of fuel blends containing demolition and construction wood
      and household waste were combusted in a small-scale experimental set-up to study
      the effect of fuel composition on the emissions of polychlorinated dibenzo-p
      dioxins (PCDDs), dibenzofurans (PCDFs), biphenyls (PCBs), chlorobenzenes (PCBzs),
      chlorophenols (PCPhs) and polycyclic aromatic hydrocarbons (PAHs). Two woody
      materials, commercial stemwood (ST) and demolition and construction wood (DC)
      were selected because of the differences in their persistent organic pollutants
      (POPs), ash and metals content. For household waste, we used a municipal solid
      waste (MSW) and a refuse-derived fuel (RDF) from MSW with 5-20 wt% and up to 5
      wt% food waste content respectively. No clear effect on the formation of
      pollutants was observed with different food waste content in the fuel blends
      tested. Combustion of ST-based fuels was very inefficient which led to high PAH
      emissions (32 +/- 3.8 mg/kgfuel). The use of DC clearly increased the total PCDD
      and PCDF emissions (71 +/- 26 MUg/kgfuel) and had a clear effect on the formation
      of toxic congeners (210 +/- 87 ng WHO2005-TEQ/kgfuel). The high PCDD and PCDF
      emissions from DC-based fuels can be attributed to the presence of material
      contaminants such as small pieces of metals or plastics as well as timber treated
      with chromated copper arsenate preservatives and pentachlorophenol in the DC
      source.

PMID- 29649693
TI  - Dry and wet ozonation of denim: Degradation products, reaction mechanism,
      toxicity and cytotoxicity assessment.
AB  - The study aims to identify the denim ozonation by-products under different
      operating conditions and investigate the chemical toxicity of these compounds via
      the inhibitory effect of the sample on the light emission of bioluminescent
      bacteria (Vibriofischeri) and on human health using the HepG2 human hepatoma cell
      line. Various by-products in treated denim extract were detected w gas
      chromatography-mass spectrometry (GC-MS) analysis. The results revealed that the
      main oxidation by-product was isatin (1H-indole-2,3-dione), which formed in
      excess amounts on wet ozonated denim. It was observed that this compound showed
      more toxicity when high ozone concentrations were used, especially in the
      presence of moisture. It exhibited a considerable antibacterial activity. EC20
      and EC50 average values of 5.55% and 13.47% were obtained with a wet ozonation
      rinse bath at 48 g/N.m3, which makes it hazardous to aquatic environments.

PMID- 29649694
TI  - Microbial synthesis of metallic molybdenum nanoparticles.
AB  - The production of nanoparticles through biosynthesis is a reliable, non-toxic,
      and sustainable alternative to conventional chemical and physical methods of
      production. While noble metals, such as palladium, gold, and silver, have been
      formed via bioreduction, biologically-induced reduction of electroactive elements
      to a metallic state has not been reported previously. Herein, we report the
      reduction of an electroactive element, molybdenum, via microbial reduction using
      Clostridium pasteurianum. C. pasteurianum was able to reduce 88% of the added
      Mo6+ ions. The bioreduced molybdenum was shown to be metallically bonded in a
      prototypical crystal structure with an average particle size of 15 nm. C.
      pasteurianum was previously shown to degrade azo dyes using in situ formed Pd
      nanoparticles, but this study shows that in situ formed Mo particles also act as
      catalysts for degradation of azo dyes. C. pasteurianum cultures with the
      bioformed Mo nanoparticles were able completely degrade 155 MUM methyl orange
      within 6 min, while controls with no Mo took 36 min. This research demonstrates,
      for the first time, that the bioreduction of active elements and formation of
      catalytic particles is achievable.

PMID- 29649695
TI  - Doctor shopping of opioid analgesics relative to benzodiazepines: A
      pharmacoepidemiological study among 11.7 million inhabitants in the French
      countries.
AB  - BACKGROUND: The abuse of prescription opioids and its subsequent consequences is
      an important public concern particularly in the USA. The literature on opioid
      analgesic abuse is scarce. OBJECTIVE: We assess the extent and risk of opioid
      analgesics abuse relative to benzodiazepines (BZD) using the doctor shopping
      method, taken into account the pharmacological characteristics (dosage, route of
      administration, extended or immediate release). METHODS: We used SNIIRAM database
      covering 11.7 million inhabitants. All individuals with at least one
      reimbursement for non-injectable opioid analgesic or BZD in 2013 were included.
      Opioids for mild to moderate pain and for moderately severe to severe pain were
      studied. The Doctor Shopping Quantity (DSQ) is the quantity obtained by
      overlapping prescriptions from several prescribers. The Doctor Shopping Indicator
      (DSI) is the DSQ divided by the total dispensed quantity. RESULTS: The strong
      opioid analgesics have the highest DSI (2.79%) versus 2.06% for BZD hypnotics.
      Flunitrazepam ranked first according to its DSI (13.2%), followed by morphine
      (4%), and zolpidem (2.2%). The three-strong opioids having the highest DSI were
      morphine, oxycodone and fentanyl (respectively 4%, 1.7% and 1.5%). The highest
      DSI was observed for the highest dosages of morphine (DSI = 8.4% for 200 mg) and
      oxycodone (DSI = 2.8% for 80 mg). The highest DSI for fentanyl was described with
      nasal and transmucosal forms (4.1% and 3.3% respectively). The highest DSI for
      morphine was described for extended-release (4.1%). CONCLUSION: There is a need
      to reinforce surveillance systems to track opioid misuse and to increase
      awareness of healthcare professionals.

PMID- 29649696
TI  - Cholecystitis secondary to gallbladder torsion - A rare case report.
AB  - INTRODUCTION: Gallbladder torsion is a rare condition of increasing prevalence in
      recent years. It is often difficult to diagnose pre-operatively and delayed
      intervention can lead to significant complications. PRESENTATION OF CASE: We
      present a case of an 81 year old lady who presented with symptoms of
      cholecystitis for 24 h with no evidence of cholelithiasis on imaging. She
      deteriorated within 24 h of admission despite intravenous antibiotics; Emergency
      laparoscopy was performed which showed the gallbladder malrotated 180  degrees 
      with features of necrosis. Laparoscopic cholecystectomy was performed without
      complications. DISCUSSION: The cause of gallbladder torsion are thought to be due
      to underlying anatomical variations or loss of elasticity associated with aging.
      Diagnosis is difficult clinically and radiologically, however, features such as
      "whirl sign" and "cystic duct knot sign" have been described. Due to ischemia
      associated with torsion, clinical vigilance and early intervention is recommended
      to prevent potential fatal sequelae particularly in the elderly population.
      CONCLUSION: Gallbladder torsion is a rare finding that can be difficult to
      diagnose clinically, we are hoping to promote awareness to prevent complications
      associated with delayed therapy.

PMID- 29649697
TI  - Intrapancereatic abscess due to arteriovenous malformation involving the entire
      pancreas: A case report and review of the literature.
AB  - INTRODUCTION: The described case is a patient with pancreatic arteriovenous
      malformation involving the entire pancreas and complicated with intrapancereatic
      abscess. PRESENTATION OF CASE: A 47 years-old was suffering from episodes of
      abdominal pain and vomiting with multiple hospital visits without reaching a
      diagnosis for four months. Contrast-enhanced computed tomography scan (CECT) done
      which shows a 1.6*1.4cm fluid collection was seen in uncinate process of the
      pancreas, Magnetic resonance imaging (MRI) demonstrates abnormal vasculature
      involving the pancreas. Therefore patient diagnosed as a case of pancreatic
      arteriovenous malformation (P-AVM), which confirmed by Selective Computed
      Tomography Angiogram (CT Angiogram). DISCUSSION: Normal investigations in the
      first attempts can lead to miss pancreatic arteriovenous malformation (P-AVM),
      and can lead to serious and fatal. CONCLUSION: Early diagnosis and treatment of
      (P-AVM) is very important even in asymptomatic patients. Conservative treatment
      in complicated and big P-AVM appears ineffective as surgical resection.

PMID- 29649698
TI  - Enantiomer-specific stable carbon isotope analysis (ESIA) to evaluate degradation
      of the chiral fungicide Metalaxyl in soils.
AB  - Chiral pesticides are often degraded enantioselectively in soils, leading to
      disparity among enantiomers that may display different toxicity levels.
      Monitoring pesticide degradation extents and processes remains out of reach in
      the field using conventional bulk and enantiomer concentration analyses.
      Enantioselective stable carbon isotope analysis (ESIA) combines compound specific
      isotope analysis (CSIA) and enantioselective analysis, and bears potential to
      distinguish enantiomer degradation from non-destructive dissipation. We developed
      ESIA of the fungicide Metalaxyl, providing the 13C/12C ratios for S-Metalaxyl and
      R-Metalaxyl separately, and applied it to follow degradation in soil incubation
      experiments. Significant enantioselective degradation (kS-MTY = 0.007-0.011 day-1
      < kR-MTY = 0.03-0.07 day-1) was associated with isotope fractionation
      (Deltadelta13CS-MTY ranging from 2 to 60/00). While R-Metalaxyl degradation was
      rapid (T1/2~10 days), concomitant enrichment in heavy isotopes of the persistent
      S-Metalaxyl occurred after 200 days of incubation (epsilonS-Metalaxyl ranging
      from -1.3 to -2.70/00). In contrast, initial racemic ratios and isotopic
      compositions were conserved in abiotic experiments, which indicates the
      predominance of microbial degradation in soils. Degradation products analysis and
      apparent kinetic isotope effect (AKIE) suggested hydroxylation as a major
      enantioselective degradation pathway in our soils. Altogether, our study
      underscores the potential of ESIA to evaluate the degradation extent and
      mechanisms of chiral micropollutants in soils.

PMID- 29649699
TI  - Visuospatial biases in preschool children: Evidence from line bisection in three
      dimensional space.
AB  - Spatial attention in adults is characterized by systematic asymmetries across all
      three spatial dimensions. These asymmetries are evident when participants bisect
      horizontal, vertical, or radial lines and misplace their midpoints to the left,
      the top, or far from the body, respectively. However, bisection errors are rarely
      examined during early childhood. In this study, we examined the development of
      spatial-attentional asymmetries in three-dimensional (3D) space by asking
      preschool children (aged 3-6 years) to bisect horizontal, vertical, and radial
      lines. Children erred to the left with horizontal lines and to the top with
      vertical lines, consistent with the pattern reported in adults. These biases got
      stronger with age and were absent in the youngest preschoolers. However, by
      controlling for a possible failure in hitting the line, we observed an additional
      unpredicted pattern: Children's pointing systematically deviated away from the
      line to an empty space on its left side (for vertical and radial lines) or above
      it (for horizontal lines). Notably, this task-irrelevant deviation was pronounced
      in children as young as 3 or 4 years. We conclude that asymmetries in spatial
      attentional functions should be measured not only in task-relevant dimensions but
      also in task-irrelevant dimensions because the latter may reveal biases in very
      young children not typically observed in task-relevant measures.

PMID- 29649700
TI  - Detailed spectral profile analysis of electrocorticograms during freezing against
      penicillin-induced epileptiform discharges in the anesthetized rat.
AB  - OBJECTIVES: Cryosurgery is an alternative technique for minimally invasive
      treatment of lesions. We have recently examined cryosurgery for epilepsy in
      animal models, and found that penicillin G (PG)-induced epileptiform discharges
      (EDs) mostly vanished after freezing. However, EDs were provoked again after
      insufficient freezing. Inadequate freezing is not visually detectable during and
      just after freezing and is not predictable beforehand. To manage this problem, we
      examined whether intraoperative monitoring of electrocorticograms (ECoGs) can
      predict recurrence of EDs after cryosurgery. METHODS: A palm-sized cryoprobe
      system was applied to focal seizures in a Wistar rat model in which EDs were
      induced in advance by intracerebral injection of PG. During stable induction of
      EDs, the cryoprobe was carefully inserted into the epileptic region and this
      region was immediately frozen. After the series of prefreezing, freezing, and
      postfreezing, rats in which PG-induced EDs relapsed within 3 h were defined as
      the ED-relapsed (EDR) group, and other rats were defined as the ED-vanished (EDV)
      group. Time-frequency analysis was conducted on the ECoGs in each group through
      each freezing series. RESULTS: Relapse of PG-induced EDs on ECoG after the
      freezing series was associated with the remaining power of the delta band in the
      freezing period more strongly in the EDR group than in the EDV group.
      CONCLUSIONS: Success or failure of the freezing procedure can be predicted by the
      specificity of the delta band of the ECoG obtained intraoperatively.

PMID- 29649701
TI  - Change of heart dimensions and function during pregnancy in goats.
AB  - The study aimed to evaluate the effect of pregnancy on heart diameters and
      function in goats. Transthoracic echocardiography of 12 female dairy goats of two
      Polish regional breeds was performed. A Mindray M7 diagnostic ultrasound system
      with Phased Array transducer was used. Simultaneously, electrocardiography was
      recorded. All animals were examined four times - at mating season, at the end of
      the first trimester, at the end of the second trimester and just before kidding.
      Eleven measurements were taken each time: aortic and left atrial diameter (AoD
      and LAD), right and left ventricular internal diameter in diastole (RVIDd and
      LVIDd), left ventricular internal diameter in systole (LVIDs), inter-ventricular
      septum thickness in diastole and systole (IVSd and IVSd) and left ventricular
      posterior wall in diastole and systole (LVPWd and LVPWs), maximum left and right
      ventricular outflow tract velocity (RVOT Vmax and LVOT Vmax). Nine consecutive
      measurements were derived: the ratio of the left atrial diameter to the aortic
      diameter (AoD/LAD), left ventricular fractional shortening (FS%), left
      ventricular ejection fraction (EF%), maximum outflow tract pressure gradients
      (RVOT PGmax and LVOT PGmax), left ventricular end-diastolic volume (LVEDV) and
      left ventricular end-systolic volume (LVESV), stroke volume (SV) and cardiac
      output (CO). HR, LAD, LVPWs, IVSs increased significantly in the first trimester.
      AoD and RVIDd were significantly higher around parturition. LVIDd, FS%, EF%, SV
      and CO rose both in the first and third trimester. No measurement decreased
      during pregnancy. The study confirms that pregnancy causes changes in the heart
      size and functioning.

PMID- 29649702
TI  - Quantitative characterization and analysis of granule transformations: Role of
      intermittent gas sparging in a super high-rate anaerobic system.
AB  - Knowledge of leveraging biomass characteristics is essential for achieving a
      microbial community with a desired structure to optimize anaerobic bioreactor
      performance. This study investigates the successive granule transformations in a
      high-rate anaerobic system with intermittent gas sparging and sequential
      increases in organic loading rates (OLRs), by establishing the correlations
      between the granule microstructures and reactor operating parameters. Over the
      course of a 196-day lab-scale trial, the granules were visualized in various
      stages using scanning electron microscopy, and digital image processing was
      applied for further quantifying their surface properties. Correlation analyses
      revealed that irregularities of the granule microstructures (surface properties,
      specific surface area and pore volume) emerged at stage 4 when the OLR was 13.31
      kg COD/m3.day and in stage 5 in the absence of gas sparging. The loading ratio
      (substrate surface loading to upward velocity) was identified to be the main
      parameter controlling the granule transformations, and the surface structures
      were classified into three categories for further interpretation. Confocal laser
      scanning microscopy analyses showed that the granule core started to hollow out
      from stage 4. It is also found that a rough granule surface helped accelerate the
      growth of the granular diameter under gas sparging. Overall, this study not only
      establish quantitative correlations between the granules microstructures and
      reactor operating parameters, but also shed light on the use of intermittent gas
      sparging to control the surface properties of anaerobic granules in high-rate
      anaerobic bioreactors.

PMID- 29649703
TI  - Modeling the exposure of wild fish to endocrine active chemicals: Potential
      linkages of total estrogenicity to field-observed intersex.
AB  - Decades of studies on endocrine disruption have suggested the need to manage the
      release of key estrogens from municipal wastewater treatment plants (WWTP).
      However, the proposed thresholds are below the detection limits of most routine
      chemical analysis, thereby restricting the ability of watershed managers to
      assess the environmental exposure appropriately. In this study, we demonstrated
      the utility of a mechanistic model to address the data gaps on estrogen exposure.
      Concentrations of the prominent estrogenic contaminants in wastewaters (estrone,
      estradiol, and ethinylestradiol) were simulated in the Grand River in southern
      Ontario (Canada) for nine years, including a period when major WWTP upgrades
      occurred. The predicted concentrations expressed as total estrogenicity (E2
      equivalent concentrations) were contrasted to a key estrogenic response (i.e.,
      intersex) in rainbow darter (Etheostoma caeruleum), a wild sentinel fish species.
      A predicted total estrogenicity in the river of >=10 ng/L E2 equivalents was
      associated with high intersex incidence and severity, whereas concentrations <0.1
      ng/L E2 equivalents were associated with minimal intersex expression. Exposure to
      a predicted river concentration of 0.4 ng/L E2 equivalents, the environmental
      quality standard (EQS) proposed by the European Union for estradiol, was
      associated with 34% (95% CI:30-38) intersex incidence and a very low severity
      score of 0.6 (95% CI:0.5-0.7). This exposure is not predicted to cause adverse
      effects in rainbow darter. The analyses completed in this study were only based
      on the predicted presence of three major estrogens (E1, E2, EE2), so caution must
      be exercised when interpreting the results. Nevertheless, this study illustrates
      the use of models for exposure assessment, especially when measured data are not
      available.

PMID- 29649704
TI  - Pesticide degradation and export losses at the catchment scale: Insights from
      compound-specific isotope analysis (CSIA).
AB  - Although pesticides undergo degradation tests prior to use, determining their
      export, degradation and persistence under field conditions remains a challenge
      for water resource management. Compound specific isotope analysis (CSIA) can
      provide evidence of contaminant degradation extent, as it is generally
      independent of non-destructive dissipation (e.g., dilution, sorption,
      volatilization) regulating environmental concentrations. While this approach has
      been successfully implemented in subsurface environments, its application to
      pesticides in near-surface hydrological contexts at catchment scale is lacking.
      This study demonstrates the applicability of CSIA to track pesticide degradation
      and export at catchment scale and identify pesticide source areas contributing to
      changes in stable isotope signature in stream discharge under dynamic
      hydrological contexts. Based on maximum shifts in carbon stable isotope
      signatures (Deltadelta13C  = 4.6 +/- 0.50/00) of S-metolachlor (S-met), a widely
      used herbicide, we estimate maximum degradation to have reached 96 +/- 3% two
      months after first application. Maximum shifts in nitrogen isotope signatures
      were small and inverse (Deltadelta15N=-1.3+/-0.60/00) indicating potential
      secondary isotope effects during degradation. In combination with a mass balance
      approach including S-met main degradation products, total catchment non
      destructive dissipation was estimated to have reached 8 +/- 7% of the applied
      product. Our results show that CSIA can be applied to evaluate natural
      attenuation of pesticides at catchment scale. By providing a more detailed
      account of pesticide dissipation and persistence under field conditions we
      anticipate the contribution of pesticide CSIA to the improvement of regulatory
      and monitoring strategies.

PMID- 29649705
TI  - In lens BSE detector with energy filtering.
AB  - We present a new type of an in-lens detector designed for Thermo Fisher
      Scientific (FEI) electron microscopes with the Elstar column. A key feature of it
      is high-pass energy filtering to enable the detection of low-loss backscattered
      electrons with their energy close to the primary beam energy. We show an
      application of the detector in imaging of a biological sample where the signal
      from these electrons leads to a significant improvement in resolution.

PMID- 29649706
TI  - Quantitative assessment for flexed-elbow deformity during gait following
      botulinum toxin A treatment.
AB  - BACKGROUND: The effect of botulinum toxin A (BoNTA) injection on flexed-elbow
      deformity is usually evaluated using the Modified Ashworth Scale (MAS), but only
      with the muscle tone at rest. Some patients show the flexed-elbow deformity
      during gait despite low muscle tone at rest. OBJECTIVE: This study aimed to
      evaluate the effect of BoNTA injection on flexed-elbow deformity during gait
      using a three-dimensional motion analysis system. METHODS: Twenty stroke patients
      with spastic flexed-elbow deformity during gait received BoNTA injections into
      the upper limb muscles. The MAS score of the elbow flexors, passive elbow range
      of motion, comfortable overground gait velocity, and elbow flexion angle during
      treadmill gait were evaluated just before and 2, 6, and 12 weeks after the
      injection. Twenty-five healthy subjects were also recruited to provide a normal
      reference of the elbow flexion angle. RESULTS: The MAS scores at 2, 6 and 12
      weeks after the injection were significantly lower than that before the
      injection. Some patients showed no spasticity at rest but an obviously flexed
      elbow during gait. The elbow flexion angles during gait at 2 and 6 weeks after
      the injection were significantly lower than that before the injection.
      CONCLUSIONS: BoNTA injections to the upper limb muscles reduced muscle tone at
      rest and flexed-elbow deformity during gait. However, the elbow flexion angle
      during gait returned to its pre-injection level sooner than the muscle tone at
      rest. We strongly recommend evaluating muscle tone during motion and at rest,
      preferably using three-dimensional motion analysis since it can objectively
      detect small changes.

PMID- 29649707
TI  - Specific smartphone usage and cognitive performance affect gait characteristics
      during free-living and treadmill walking.
AB  - BACKGROUND: Mobile phone tasks like texting, typing, and dialling during walking
      are known to impact gait characteristics. Beyond that, the effects of performing
      smartphone-typical actions like researching and taking self-portraits (selfie) on
      gait have not been investigated yet. RESEARCH QUESTION: We aimed to investigate
      the effects of smartphone usage on relevant gait characteristics and to reveal
      potential association of basic cognitive and walking plus smartphone dual-task
      abilities. METHODS: Our cross-sectional, cross-over study on physically active,
      healthy participants was performed on two days, interrupted by a 24-h washout in
      between. Assessments were: 1) Cognitive testing battery consisting of the trail
      making test (TMT A and B) and the Stroop test 2) Treadmill walking under five
      smartphone usage conditions: no use (control condition), reading, dialling,
      internet searching and taking a selfie in randomized order. Kinematic and kinetic
      gait characteristics were assessed to estimate conditions influence. RESULTS: In
      our sample of 36 adults (24.6 +/- 1 years, 23 female, 13 male), ANCOVAs followed
      by post-hoc t-tests revealed that smartphone usage impaired all tested gait
      characteristics: gait speed (decrease, all conditions): F = 54.7, p < 0.001;
      cadence (increase, all): F = 38.3, p < 0.001; double stride length (decrease,
      all): F = 33.8, p < 0.001; foot external rotation (increase during dialling,
      researching, selfie): F = 16.7, p < 0.001; stride length variability (increase):
      F = 11.7, p < 0.001; step width variability (increase): F = 5.3, p < 0.001; step
      width (Friedmann test and Wilcoxon Bonferroni-Holm-corrected post-hoc analyses,
      increase): Z = -2.3 to -2.9; p < 0.05); plantar pressure proportion (increase
      during reading and researching) (Z = -2.9; p < 0.01). The ability to keep usual
      gait quality during smartphone usage was systematically associated with the TMT B
      time regarding cadence and double stride length for reading (r = -0.37), dialling
      (r = -0.35) and taking a selfie (r = -0.34). SIGNIFICANCE: Smartphone usage
      substantially impacts walking characteristics in most situations. Changes of gait
      patterns indicate higher cognitive loads and lower awareness.

PMID- 29649708
TI  - A systematic review and meta-analysis on the efficacy of Internet-delivered
      behavioral activation.
AB  - BACKGROUND: Behavioral activation (BA) is an evidence-based treatment for
      depression which has attracted interest and started to accumulate evidence for
      other conditions when delivered face-to-face. Due to its parsimoniousness, it is
      suitable to be delivered via the Internet. The goal of this systematic review and
      meta-analysis was to examine evidence from randomized controlled trials (RCTs) to
      determine the efficacy of Internet-based BA and assess the quality of this
      evidence. METHODS: Studies were identified from electronic databases (EMBASE, ISI
      Web of Knowledge, Medline, CINHAL, PsychINFO, Cochrane) and reference lists of
      included studies. Two reviewers independently screened articles for inclusion and
      extracted data. They assessed the quality of evidence for each outcome using The
      Grading of Recommendations Assessment, Development and Evaluation framework.
      RESULTS: Nine RCTs on different forms of depression were included with 2157 adult
      participants. Random effects meta-analyses showed that in non-clinical settings,
      guided Internet-based BA was non-inferior to other forms of behavioral therapy
      and mindfulness (mainly very low to low quality evidence) and superior to
      physical activity (very low quality evidence), psychoeducation/treatment as usual
      (moderate quality evidence) and waitlist (low quality evidence) at reducing
      depression and anxiety outcomes at post-treatment and short follow-up.
      LIMITATIONS: The poor quality of some of the findings means that results should
      be cautiously interpreted. CONCLUSIONS: Evidence for the efficacy of Internet
      based BA as a treatment for depression is promising. However, high quality
      studies with longer follow-ups are needed to increase confidence in findings and
      determine its efficacy in clinical settings and other conditions.

PMID- 29649709
TI  - The relationship between the dietary inflammatory index (DII(r)) and incident
      depressive symptoms: A longitudinal cohort study.
AB  - BACKGROUND: Diet is a common source of inflammation, and inflammation is
      associated with depression. We examined the association between the dietary
      inflammatory index (DII(r)), a validated measure of inflammatory potential of the
      diet, and risk of depression in a cohort of older North American adults. METHODS:
      This longitudinal study, with a follow-up of 8 years, included 3648 participants
      (1577 males, 2071 females; mean age: 60.6 years) with/at risk of knee
      osteoarthritis. DII(r) scores were calculated using the validated Block Brief
      2000 Food-Frequency Questionnaire. Center for Epidemiological Studies Depression
      20 scale was used to define depressive symptoms. The relationship between
      baseline DII(r) score and incident depression was assessed through Cox's
      regression analysis, adjusted for potential confounders, and reported as hazard
      ratios (HRs). RESULTS: In total, 837 individuals (310 men and 527 women)
      developed incident depressive symptoms over the course of 8 years. Participants
      in the most pro-inflammatory group (quartile 4) had approximately 24% higher risk
      of developing depressive symptoms compared to subjects with the most anti
      inflammatory diet (HR: 1.24; 95% CI: 1.01-1.53; p = 0.04). CONCLUSION: These
      results suggest that a pro-inflammatory diet may be associated with higher
      incidence of depressive symptoms in a cohort of older Americans. Transitioning to
      a more anti-inflammatory diet may reduce depression risk.

PMID- 29649710
TI  - Psychometric properties of the concise health risk tracking (CHRT) in adolescents
      with suicidality.
AB  - BACKGROUND: Several self-report rating scales have been developed to assess
      suicidal ideation, yet few examine other factors related to increased suicidal
      risk, and even fewer have been validated in both adolescents and adults. We
      evaluate the 14-item Concise Health Risk Tracking - Self Report (CHRT-SR), a
      measure previously validated in adults, in a sample of adolescents at risk for
      suicide. METHOD: Data are from a retrospective chart review of adolescents
      treated in an intensive outpatient program for youth with severe suicidality.
      Teens completed the CHRT-SR and Quick Inventory of Depressive Symptomatology -
      Adolescents (QIDS-A) at baseline and discharge. The CHRT-SR was evaluated to
      determine the factor validity, internal consistency, construct validity, and
      sensitivity to change. RESULTS: Adolescents (n = 271) completed the CHRT-SR prior
      to treatment, and 231 completed the CHRT-SR at discharge. Three factors were
      identified with excellent model fit: Propensity, Impulsivity, and Suicidal
      Thoughts. Internal consistency reliability coefficients were good-to-excellent
      for the total score and all three factors at baseline (a = 0.774-0.915) and exit
      (a = 0.849-0.941). The total score and all three factors significantly correlated
      with overall depression severity and suicidal ideation as rated by teens and
      parent (p = .704-0.756, all p < .001). The CHRT-SR was sensitive to change, with
      moderate to large effect sizes (Cohen's d = 0.599-1.062). LIMITATIONS: Study
      limitations include generalizability, lack of a control group, and retrospective
      data from a sample of opportunity. CONCLUSIONS: The CHRT-SR is a reliable and
      valid measure for examining severity of suicidal thoughts and associated risk
      factors, and is sensitive to change following an intervention in adolescents.

PMID- 29649711
TI  - The interaction of BDNF Val66Met, PTSD, and child abuse on psychophysiological
      reactivity and HPA axis function in a sample of Gulf War Veterans.
AB  - INTRODUCTION: While the BDNF Val66Met polymorphism has been linked to various
      psychological disorders, limited focus has been on its relationship to
      posttraumatic stress disorder (PTSD) and early traumas such as child abuse.
      Therefore, we assessed whether Val66Met was associated with fear potentiated
      psychophysiological response and HPA axis dysfunction and whether PTSD status or
      child abuse history moderated these outcomes in a sample of Veterans. METHODS:
      226 and 173 participants engaged in a fear potentiated acoustic startle paradigm
      and a dexamethasone suppression test (DST) respectively. Fear conditions included
      no, ambiguous, and high threat conditions. Psychophysiological response measures
      included electromyogram (EMG), skin conductance response (SCR), and heart rate.
      The Clinician Administered PTSD Scale (CAPS) and the Trauma History Questionnaire
      (THQ) were used to assess PTSD status and child abuse history respectively.
      RESULTS: Met allele carriers exhibited greater SCR magnitudes in the no and
      ambiguous threat conditions (p < 0.01 and p < 0.05 respectively). Met carriers
      with PTSD exhibited greater physiological response magnitudes in the ambiguous
      (SCR, p < 0.001) and high threat conditions (SCR and heart rate, both p <=
      0.005). Met carrier survivors of child abuse exhibited blunted heart rate
      magnitudes in the high threat condition (p < 0.01). Met allele carries with PTSD
      also exhibited greater percent cortisol suppression (p < 0.005). LIMITATIONS:
      Limitations included small sample size and the cross-sectional nature of the
      data. CONCLUSIONS: The Val66met may impact PTSD susceptibility differentially via
      enhanced threat sensitivity and HPA axis dysregulation. Child abuse may moderate
      Val66Met's impact on threat reactivity. Future research should explore how
      neuronal mechanisms might mediate this risk.

PMID- 29649712
TI  - Sexual abuse but not posttraumatic stress disorder is associated with
      neurocognitive deficits in South African traumatized adolescents.
AB  - OBJECTIVES: Neurocognitive impairments are commonly observed in adults suffering
      from posttraumatic stress disorder (PTSD). The picture is less clear in
      adolescents. Childhood sexual abuse (CSA) may have an independent influence on
      neuropsychological test performance and provide partial explanatory power of the
      inconsistent findings. We hypothesized that adolescents with PTSD who have also
      suffered sexual abuse would have most pronounced deficits on neurocognitive
      testing. METHODS: In a cross-sectional design, 105 traumatized South African
      adolescents, of whom 52 fulfilled criteria of PTSD and 34 reported CSA, were
      studied. A comprehensive neurocognitive battery including tests of memory,
      executive functioning, and language was used to analyze the associations of
      neurocognitive impairments with PTSD and CSA. RESULTS: Adolescents reporting CSA
      manifested impairments in proactive and retroactive interference tasks on the Rey
      Auditory Verbal Learning test and in the copy condition of the Rey Osterrieth
      figure test, indicating deficits in attention and working memory. Against our
      hypothesis, no independent effects of PTSD were found on neurocognitive
      performance. Results were independent of comorbid psychiatric diagnoses.
      CONCLUSIONS: Sexual abuse seems to have an independent influence on attention and
      working memory. This could be an early sign of hippocampal impairment.

PMID- 29649713
TI  - Corrigendum to "Gas/particle partitioning and particle size distribution of
      PCDD/Fs and PCBs in urban ambient air" [Sci. Total Environ. 624 (2018) 170-179].

PMID- 29649714
TI  - Effects of urban form on the urban heat island effect based on spatial regression
      model.
AB  - The urban heat island (UHI) effect is becoming more of a concern with the
      accelerated process of urbanization. However, few studies have examined the
      effect of urban form on land surface temperature (LST) especially from an urban
      planning perspective. This paper used spatial regression model to investigate the
      effects of both land use composition and urban form on LST in Wuhan City, China,
      based on the regulatory planning management unit. Landsat ETM+ image data was
      used to estimate LST. Land use composition was calculated by impervious surface
      area proportion, vegetated area proportion, and water proportion, while urban
      form indicators included sky view factor (SVF), building density, and floor area
      ratio (FAR). We first tested for spatial autocorrelation of urban LST, which
      confirmed that a traditional regression method would be invalid. A spatial error
      model (SEM) was chosen because its parameters were better than a spatial lag
      model (SLM). The results showed that urban form metrics should be the focus for
      mitigation efforts of UHI effects. In addition, analysis of the relationship
      between urban form and UHI effect based on the regulatory planning management
      unit was helpful for promoting corresponding UHI effect mitigation rules in
      practice. Finally, the spatial regression model was recommended to be an
      appropriate method for dealing with problems related to the urban thermal
      environment. Results suggested that the impact of urbanization on the UHI effect
      can be mitigated not only by balancing various land use types, but also by
      optimizing urban form, which is even more effective. This research expands the
      scientific understanding of effects of urban form on UHI by explicitly analyzing
      indicators closely related to urban detailed planning at the level of regulatory
      planning management unit. In addition, it may provide important insights and
      effective regulation measures for urban planners to mitigate future UHI effects.

PMID- 29649715
TI  - Influences of model structure and calibration data size on predicting chlorine
      residuals in water storage tanks.
AB  - This study evaluated the influences of model structure and calibration data size
      on the modelling performance for the prediction of chlorine residuals in
      household drinking water storage tanks. The tank models, which consisted of two
      modules, i.e., hydraulic mixing and water quality modelling processes, were
      evaluated under identical calibration conditions. The hydraulic mixing modelling
      processes investigated included the continuously stirred tank reactor (CSTR) and
      multi-compartment (MC) methods, and the water quality modelling processes
      included first order (FO), single-reactant second order (SRSO), and variable
      reaction rate coefficients (VRRC) second order chlorine decay kinetics. Different
      combinations of these hydraulic mixing and water quality methods formed six tank
      models. Results show that by applying the same calibration datasets, the tank
      models that included the MC method for modelling the hydraulic mixing provided
      better predictions compared to the CSTR method. In terms of water quality
      modelling, VRRC kinetics showed better predictive abilities compared to FO and
      SRSO kinetics. It was also found that the overall tank model performance could be
      substantially improved when a proper method was chosen for the simulation of
      hydraulic mixing, i.e., the accuracy of the hydraulic mixing modelling plays a
      critical role in the accuracy of the tank model. Advances in water quality
      modelling improve the calibration process, i.e., the size of the datasets used
      for calibration could be reduced when a suitable kinetics method was applied.
      Although the accuracies of all six models increased with increasing calibration
      dataset size, the tank model that consisted of the MC and VRRC methods was the
      most suitable of the tank models as it could satisfactorily predict chlorine
      residuals in household tanks by using invariant parameters calibrated against the
      minimum dataset size.

PMID- 29649716
TI  - The relation between land use and subsidence in the Vietnamese Mekong delta.
AB  - The Vietnamese Mekong delta is subsiding due to a combination of natural and
      human-induced causes. Over the past several decades, large-scale anthropogenic
      land-use changes have taken place as a result of increased agricultural
      production, population growth and urbanization in the delta. Land-use changes can
      alter the hydrological system or increase loading of the delta surface,
      amplifying natural subsidence processes or creating new anthropogenic subsidence.
      The relationships between land use histories and current rates of land subsidence
      have so far not been studied in the Mekong delta. We quantified InSAR-derived
      subsidence rates for the various land-use classes and past land-use changes using
      a new, optical remote sensing-based, 20-year time series of land use. Lowest mean
      subsidence rates were found for undeveloped land-use classes, like marshland and
      wetland forest (~6-7mmyr-1), and highest rates for areas with mixed-crop
      agriculture and cities (~18-20mmyr-1). We assessed the relationship strength
      between current land use, land-use history and subsidence by predicting
      subsidence rates during the measurement period solely based on land-use history.
      After initial training of all land-use sequences with InSAR-derived subsidence
      rates, the land-use-based approach predicted 65-92% of the spatially varying
      subsidence rates within the measurement error range of the InSAR observations
      (RMSE=5.8mm). As a result, the spatial patterns visible in the observed
      subsidence can largely be explained by land use. We discuss in detail the
      dominant land-use change pathways and their indirect, causal relationships with
      subsidence. Our spatially explicit evaluation of these pathways provides valuable
      insights for policymakers concerned with land-use planning in both subsiding and
      currently stable areas of the Mekong delta and similar systems.

PMID- 29649717
TI  - Drought evaluation using the GRACE terrestrial water storage deficit over the
      Yangtze River Basin, China.
AB  - Droughts are some of the worst natural disasters that bring significant water
      shortages, economic losses, and adverse social consequences. Gravity Recovery and
      Climate Experiment (GRACE) satellite data are widely used to characterize and
      evaluate droughts. In this work, we evaluate drought situations in the Yangtze
      River Basin (YRB) using the GRACE Texas Center for Space Research (CSR) mascon
      (mass concentration) data from 2003 to 2015. Drought events are identified by
      water storage deficits (WSDs) derived from GRACE data, while the drought severity
      evaluation is based on the water storage deficit index (WSDI), standardized WSD
      time series, and total water storage deficit (TWSD). The WSDI is subsequently
      compared with the Palmer drought severity index (PDSI), standardized
      precipitation index (SPI), standardized precipitation evapotranspiration index
      (SPEI), and standardized runoff index (SRI). The results indicate the YRB
      experienced increased wetness during the study period, with WSD values increasing
      at a rate of 5.20mm/year. Eight drought events are identified, and three major
      droughts occurred in 2004, 2006, and 2011, with WSDIs of -2.05, -2.38, and -1.30
      and TWSDs of -620.96mm, -616.81mm, and -192.44mm, respectively. Our findings
      suggest that GRACE CSR mascon data can be used effectively to assess drought
      features in the YRB and that the WSDI facilitates robust and reliable
      characterization of droughts over large-scale areas.

PMID- 29649718
TI  - Causes of the different behaviour of the shoreline on beaches with similar
      characteristics. Study case of the San Juan and Guardamar del Segura beaches,
      Spain.
AB  - Storms can alter the beach shape, relocating large volumes of sediments and
      generating drastic changes in the coastline. In the last 60years, beaches
      shoreline behaviour has been different even though the energy of the waves was
      similar. Therefore, it is necessary to understand the factors that affect the
      sandy coasts for better future management. In this research, two beaches, with
      different erosion rate, located in the southeast of Spain (separated by only 40km
      of distance) have been studied. The beaches: i) have similar orientations, ii)
      are open to waves with similar sand lengths of 9.8km and 6.6km, and iii) have
      similar median sediment size (D50). For its study, shoreline evolution has been
      analysed from 1956 to 2017. From the results obtained, it can be seen that: i)
      Between 1992 and 2017, San Juan just lost 3% of its surface, while in the
      previous period (1956-1990) it was 50%, and ii) Guardamar surface lost in 1992
      2017 was 18%, and in the previous period it was 14%. For the analysis of the
      agents involved in both beaches, cross-shore profiles (volume), marine climate,
      biocenosis and sedimentology studies were carried out. The results showed that
      the energy on both beaches was very similar. The biocenosis had not changed and,
      however, the morphology of Guardamar seabed had increased to 1m deep in some
      places, which had caused part of the beach berm erosion. Furthermore, important
      differences were found from the sedimentological study, concluding that the
      content of calcites and the degree of homogeneity of the particles are the real
      factors that caused these two beaches to behave differently against erosion.

PMID- 29649719
TI  - Determining the macroinvertebrate community indicators and relevant environmental
      predictors of the Hun-Tai River Basin (Northeast China): A study based on
      community patterning.
AB  - It is essential to understand the patterning of biota and environmental
      influencing factors for proper rehabilitation and management at the river basin
      scale. The Hun-Tai River Basin was extensively sampled four times for
      macroinvertebrate community and environmental variables during one year. Self
      Organizing Maps (SOMs) were used to reveal the aggregation patterns of the 355
      samples. Three community types (i.e., clusters) were found (at the family level)
      based on the community composition, which showed a clearly gradient by combining
      them with the representative environmental variables: minimally impacted source
      area, intermediately anthropogenic impacted sites, and highly anthropogenic
      impacted downstream area, respectively. This gradient was corroborated by the
      decreasing trends in density and diversity of macroinvertebrates. Distance from
      source, total phosphorus and water temperature were identified as the most
      important variables that distinguished the delineated communities. In addition,
      the sampling season, substrate type, pH and the percentage of grassland were also
      identified as relevant variables. These results demonstrated that
      macroinvertebrates communities are structured in a hierarchical manner where
      geographic and water quality prevail over temporal (season) and habitat
      (substrate type) features at the basin scale. In addition, it implied that the
      local-scale environment variables affected macroinvertebrates under the
      longitudinal gradient of the geographical and anthropogenic pressure. More than
      one family was identified as the indicator for each type of community. Abundance
      contributed significantly for distinguishing the indicators, while Baetidae with
      higher density indicated minimally and intermediately impacted area and lower
      density indicated highly impacted area. Therefore, we suggested the use of
      abundance data in community patterning and classification, especially in the
      identification of the indicator taxa.

PMID- 29649720
TI  - Differential release of cell-signaling metabolites by male and female bovine
      embryos cultured in vitro.
AB  - Male and female early bovine embryos show dimorphic transcription that impacts
      metabolism. Individual release of metabolites was examined in a 24h single
      culture medium from Day-6 male and female morulae that developed to Day-7
      expanded blastocysts. Embryos were produced in vitro, fertilized with a single
      bull and cultured in SOFaaci+6  g/L BSA. The embryonic sex was identified
      (amelogenin gene amplification). Embryos (N = 10 males and N = 10 females) and N
      = 6 blank samples (i.e. SOFaaci+6  g/L BSA incubated with no embryos) were
      collected from 3 replicates. Metabolome was analyzed by UHPLC-TOF-MS in spent
      culture medium. After tentative identification, N = 13 metabolites significantly
      (P < 0.05; ANOVA) differed in their concentrations between male and female
      embryos, although N = 10 of these metabolites showed heterogeneity (Levene's
      test; P > 0.05). LysoPC(15:0) was the only metabolite found at higher
      concentration in females (fold change [FC] male to female = 0.766). FC of
      metabolites more abundant in male culture medium (N = 12) varied from 1.069 to
      1.604. Chemical taxonomy grouped metabolites as amino-acids and related compounds
      (DL-2 aminooctanoic acid, arginine, 5-hydroxy-l-tryptophan, and
      palmitoylglycine); lipids (2-hexenoylcarnitine; Lauroyl diethanolamide; 5,6
      dihydroxyprostaglandin F1a; LysoPC(15:0); DG(14:0/14:1(9Z)/0:0) and
      triterpenoid); endogenous amine ((S)-N-Methylsalsolinol/(R)-N-Methylsalsolinol);
      n-acyl-alpha-hexosamine (N-acetyl-alpha-d-galactosamine 1-phosphate); and dUMP, a
      product of pyrimidine metabolism. Among the compounds originally contained in CM,
      female embryos significantly depleted more arginine than males and blank controls
      (P < 0.001). Male and female embryos induce different concentrations of
      metabolites with potential signaling effects. The increased abundance of
      metabolites released from males is consistent with the higher metabolic activity
      attributed to such blastocysts.

PMID- 29649722
TI  - Long-term incidence and recurrence of common mental disorders after abortion. A
      Dutch prospective cohort study.
AB  - In a previous study (Van Ditzhuijzen et al., 2017) we investigated the incidence
      and recurrence of mental disorders 2.5 to 3 years post-abortion. The aim of the
      current study was to extend these findings with longer term follow up data, up
      until 5-6 years post-abortion. We compared data of women who had had an abortion
      of the Dutch Abortion and Mental Health Study (DAMHS) to women who did not have
      an abortion from the Netherlands Mental Health Survey and Incidence Study-2
      (NEMESIS-2) (Ntotal = 2227). We used 1-to-1 matching on background confounding
      variables and measured post-abortion incidence and recurrence of common DSM-IV
      mental disorders (mood, anxiety, and substance use disorders) using the Composite
      International Diagnostic Interview (CIDI) version 3.0. After matching on
      confounding variables, abortion did not increase the likelihood that women had
      incident or recurrent mental disorders in the 5-6 years post-abortion (any
      incident mental disorder: OR = 3.66, p = .16; any recurrent mental disorder: OR =
      0.22, p = .47). We found no evidence that experiencing an abortion increases the
      risk on new or recurrent mental disorders on the longer term.

PMID- 29649721
TI  - Effect of season on reproductive behaviors and fertilization success in cavies
      (Cavia aperea).
AB  - Finding the optimal timing for breeding is crucial for small mammals to ensure
      survival and maximize lifetime reproductive success. Species living in temperate
      regions therefore often restrict breeding to seasons with favorable food and
      weather conditions. Although caviomorph rodents such as guinea pigs are described
      as non-seasonal breeders, a series of recent publications has shown seasonal
      adaptations in litter size, offspring birth mass and maternal investment. Here,
      we aim to test if seasonal patterns of litter size variation found in earlier
      studies, are mediated by seasonal differences in female estrus length,
      fertilization rate and mating behavior. The female estrus period was longer in
      fall compared to all other seasons (p < 0.001), frequently lasting 7-9 days while
      estrus in spring usually lasted less than 2 days. In fall, females mated later
      during estrus (p < 0.001), resulting in reduced fertilization rates (p < 0.001).
      Fertilization rate was well above 95% in summer while it dropped to less than 85%
      in fall and winter. While none of the male mating characteristics such as number
      and duration of copulations differed across seasons, the number of mating bouts
      was reduced in fall (p = 0.04). Finally, the developmental stages of flushed
      embryos were more diverse in spring and summer compared to fall and winter. These
      results suggest that seasonal differences in fertilization rate and quality of
      implanted embryos are mediated by female estrus length and timing and intensity
      of mating behavior. Together, these effects contribute to the observed
      differences in litter size across seasons.

PMID- 29649723
TI  - The relevance of attention deficit hyperactivity disorder in self-limited
      childhood epilepsy with centrotemporal spikes.
AB  - In this study, we aimed to evaluate the attentional and executive functions in
      patients with benign childhood epilepsy with centrotemporal spikes (BCECTS) with
      and without attention-deficit hyperactivity disorder (ADHD) compared with
      controls and compared with patients with ADHD without epilepsy. We evaluated 12
      patients with BCECTS and ADHD (66.7% boys; mean age of 9.67years); 11 children
      with non-ADHD BCECTS (63.6% boys; mean age of 11.91years); 20 healthy children
      (75% boys; mean age of 10.15years); and 20 subjects with ADHD without epilepsy
      (60% boys; mean age of 10.9years). We used a comprehensive battery of
      neuropsychological tests to evaluate attentional and executive functions in their
      broad domains. Patients with BCECTS and ADHD had worse performance in Conners'
      Continuous Performance Test II (reaction time standard error [p=0.008],
      variability [p=0.033], perseverations [p=0.044] and in reaction time interstimuli
      interval [p=0.016]). Patients with ADHD showed worse performance in Trail Making
      Test B errors [p=0.012]. In conclusion, patients with BCECTS and ADHD had worse
      executive and attentional performance compared with controls than non-ADHD
      patients with BCECTS. Regardless of the presence of epilepsy, ADHD also
      negatively impacted executive and attentional functions but in different
      executive subdomains compared with patients with epilepsy.

PMID- 29649724
TI  - Evaluation of upper limb movements in children with Down's syndrome: A systematic
      review.
AB  - : The aim of the present study was to perform a review of the literature on
      current quantitative clinical methods for the evaluation of upper limb movements
      in children and adolescents with Down syndrome, with a focus on describing the
      variables, protocols, motor function and motor control. METHODS: A survey of
      PubMed, Scielo, BVS Bireme and PEDro databases using the following key words:
      upper limb and EMG and Down syndrome; upper limb and kinematics and Down
      syndrome; upper limb and motion analysis and Down syndrome; movement and upper
      limb and Down syndrome; upper limb and Down syndrome; reach and Down syndrome.
      RESULTS: In all, 344 articles and five were selected to compose the present
      systematic review. No standardization was found among the studies analyzed with
      regard to data collection, data processing or procedures for the evaluation of
      the variables. CONCLUSION: A kinematic evaluation is effective for the discussion
      of the results, but methodological differences among the studies and inconsistent
      results exert a negative influence on clinical interpretations and the
      possibility of reproducibility. The standardization of an upper limb movement
      evaluation protocol using kinematic analysis is important, as it would provide
      the basis for comparable, reproducible results and facilitate the planning of
      treatment interventions.

PMID- 29649725
TI  - Production of live fish derived from frozen germ cells via germ cell
      transplantation.
AB  - The conservation of endangered fish is an urgent issue. Although cryo-banking of
      fish gametes might ultimately help conserve endangered fish, cryopreservation of
      fish eggs or embryos is still not possible due to their large size and high yolk
      content. Therefore, as an alternative, we focused on undifferentiated germ cells,
      such as primordial germ cells, spermatogonia, and oogonia, as materials for
      cryopreservation. Transplantation of cryopreserved germ cells into the body
      cavity of allogeneic or xenogeneic recipients sterilized by triploidization or
      endogenous germ cell ablation resulted in migration of the transplanted germ
      cells toward the recipient genital ridges, where they were eventually
      incorporated. The donor-derived germ cells initiated either spermatogenesis or
      oogenesis in the recipient gonads, depending on the sex of the recipient.
      Furthermore, by mating the male and female recipients, viable offspring derived
      from the frozen germ cells were produced. Although this technology was
      established using salmonid fish, we found that it is applicable to a wide range
      of fish species. Thus, this method might represent a "silver bullet" for
      preserving the valuable genetic resources of endangered fish species.

PMID- 29649726
TI  - Conversion and recovery of saponifiable lipids from microalgae using a nonpolar
      solvent via lipase-assisted extraction.
AB  - A single-step method for transesterifying and recovering lipids in concentrated
      slurries (ca 20% w/w solids) of ruptured microalgae is presented. A soluble
      Rhizomucor miehei lipase (RML) was used to directly transesterify the lipids in
      the marine microalgae Nannochloropsis salina. This allowed both triglycerides
      (TAG) and polar saponifiable lipids to be recovered as fatty acid methyl esters
      (FAME) using a nonpolar solvent (hexane). Up to 90 wt% of the total saponifiable
      lipids (SL) were converted to FAME within 24 h, approximately 75% of which was
      recovered in the hexane by centrifugation. Two pathways for the conversion and
      recovery of polar lipids were identified. The water in the slurry buffered
      against potential lipase inhibition by methanol, but necessitated a high methanol
      dose for maximal FAME conversion. Nonetheless the method enables the recovery of
      polar lipids as FAME while avoiding the need for both drying of the biomass and a
      downstream transesterification step.

PMID- 29649727
TI  - Optimization of sodium hydroxide pretreatment and enzyme loading for efficient
      hydrolysis of rice straw to improve succinate production by metabolically
      engineered Escherichia coli KJ122 under simultaneous saccharification and
      fermentation.
AB  - Rice straw was pretreated with sodium hydroxide (NaOH) before subsequent use for
      succinate production by Escherichia coli KJ122 under simultaneous
      saccharification and fermentation (SSF). The NaOH pretreated rice straw was
      significantly enhanced lignin removal up to 95%. With the optimized enzyme
      loading of 4% cellulase complex + 0.5% xylanase (endo-glucanase 67 CMC-U/g, beta
      glucosidase 26 pNG-U/g and xylanase 18 CMC-U/g dry biomass), total sugar
      conversion reached 91.7 +/- 0.8% (w/w). The physicochemical analysis of NaOH
      pretreated rice straw indicated dramatical changes in its structure, thereby
      favoring enzymatic saccharification. In batch SSF, succinate production of 69.8
      +/- 0.3 g/L with yield and productivity of 0.84 g/g pretreated rice straw and
      0.76 +/- 0.02 g/L/h, respectively, was obtained. Fed-batch SSF significantly
      improved succinate concentration and productivity to 103.1 +/- 0.4 g/L and 1.37
      +/- 0.07 g/L/h with a comparable yield. The results demonstrated a feasibility of
      sequential saccharification and fermentation of rice straw as a promising process
      for succinate production in industrial scale.

PMID- 29649728
TI  - Enhanced phenol removal in an innovative lignite activated coke-assisted
      biological process.
AB  - In this study, a lignite activated coke (LAC)-assisted activated sludge (AS)
      process was developed for enhancing biodegradation of phenol, while the effects
      of LAC on sludge properties and microbial community structure were investigated.
      It was found that more than 90% of phenol was removed within 1 h in the LAC/AS,
      which was 3 times higher than the conventional AS process. Moreover, the floc
      size and settleability were also significantly improved in the LAC/AS. These
      results suggested that LAC could serve as the nucleating agent to promote the
      formation of compact floc, which was beneficial for toxicity mitigation and
      system stability. The microbial community analysis by 16S high-throughput
      pyrosequencing technology further revealed a more abundant bacterial richness and
      diversity in the LAC/AS process loaded with phenol, while some phenol degraders,
      such as Propionibacteriaceae were enriched. Engineering implications further
      suggests the LAC-assisted AS process is technically sound and economically
      viable.

PMID- 29649729
TI  - Combined bioaugmentation with anaerobic ruminal fungi and fermentative bacteria
      to enhance biogas production from wheat straw and mushroom spent straw.
AB  - Bioaugmentation with anaerobic ruminal fungi and a pool of hydrogen-producing
      fermenting bacteria was tested on wheat straw (WS) and mushroom spent straw (MSS)
      with the aim of improving anaerobic digestion performance. Batch tests were set
      up to simulate a Bioaugmentation Anaerobic Digestion (BAD) treatment comparing
      single- (I-BAD) and two-stage (II-BAD) process configurations, at two reactor
      scales, 120 and 1200 ml (*10). In both cases, higher CH4 cumulative production
      was obtained in the II-BAD configuration on WS (65.1 +/- 8.9 Nml and 922 +/- 73.8
      Nml respectively). The II-BADx10 tests allowed increasing CH4 production (?290%
      and ?330% on WS and MSS, respectively) when compared to the unaugmented
      condition. Final results highlighted the achievable advantages of the two stage
      configuration in terms of CH4 production enhancement. Microbial community
      investigations confirmed the efficiency of the bioaugmentation treatment and
      revealed that such a result was mainly related to the Methanosarcinales increase,
      mostly composed by Methanosaeta.

PMID- 29649730
TI  - Rapid and high-performance adsorptive removal of hazardous acridine orange from
      aqueous environment using Abelmoschus esculentus seed powder: Single- and multi
      parameter optimization studies.
AB  - In this research, the performance of naturally abundant lignocellulosic by
      product, Abelmoschus esculentus, and its processed seed powder referred as AESP,
      as a potential biosorbent for the removal of acridine orange (AO) from the
      aqueous environment was examined. The AESP biosorbent was characterized by field
      emission scanning electron microscopy (FESEM), X-ray diffraction (XRD) analysis,
      diffuse reflectance spectroscopy (DRS), Fourier transform infrared (FTIR) and
      pHZPC analyses. The average size of the biosorbent according to particle size
      distribution analysis was found to be ~132 MUm. The batch adsorption experiments
      were conducted by altering the parameters such as contact time, solution pH,
      biosorbent dosage, initial dye concentration, stirring speed and temperature.
      Sorption of cationic AO dye onto AESP was found to be rapid, and the equilibrium
      condition reached within 30 min. The isotherms (Langmuir, Freundlich, Redlich
      Peterson and Sips), kinetic models (pseudo-first order, pseudo-second order,
      Elovich, intra-particle diffusion, Bangham and modified-Freundlich models) and
      thermodynamic parameters were also evaluated. High values of determination
      coefficients (R2) and minimal values of non-linear error functions (i.e. HYBRD,
      RMSE, MPSD, ARE, APE and chi2) indicated that experimental data were best fitted
      with Sips isotherm and pseudo-second order kinetic model. Accordingly, the
      maximum loading capacity of AESP was found to be 259.4, 284.3 and 346.5 mg/g for
      the temperatures of 15, 30 and 45  degrees C, respectively. The thermodynamic
      parameters showed that the adsorption of AO onto the AESP surface was an
      endothermic and spontaneous process. Besides these, the central composite
      experimental design (CCD) superimposed with response surface methodology (RSM)
      modeling was also employed to investigate the effect of four significant
      parameters (solution pH, contact time, initial AO concentration and AESP dosage)
      and their interaction-term effects on the adsorption capacity of AESP and to
      formulate the mathematical model for the experimental data using multi-variate
      statistical analysis. Maximum dye uptake capacity under the optimum conditions of
      variables (pH 8.96, contact time 32.06 min, initial dye concentration 867.71 mg/L
      and AESP dosage 1.89 g/L) was 312.1 mg/g at temperature 30  degrees C, and it was
      found to be very close to the experimentally determined values (313.4 +/- 0.057
      mg/g). The promising reusability potential of AESP using 0.1 M HCl, implied that,
      the lignocellulosic biosorbent AESP might be helpful for the appropriate
      designing of the environmental-friendly purification systems.

PMID- 29649731
TI  - Adsorption-desorption of dimethenamid and fenarimol onto three agricultural soils
      as affected by treated wastewater and fresh sewage sludge-derived dissolved
      organic carbon.
AB  - The use of treated wastewaters (TWW) in agriculture is widening in areas
      suffering drought, such as southern Europe, to preserve freshwater supply for
      human consumption. The composition of TWW, especially concerning their organic
      carbon (OC) content, has been demonstrated to influence the processes governing
      the behavior of non-ionic pesticides in soils. Three OC-poor agricultural soils
      (SV, RM1 and RM3) from the province of Granada (Spain) were chosen for the
      assessment of the adsorption and desorption of the herbicide dimethenamid (DIM)
      and the fungicide fenarimol (FEN). TWW and sewage sludge extracts at different
      dissolved OC (DOC) concentrations (30, 90 and 300 mg L-1) were considered to
      evaluate their effect on pesticide adsorption-desorption. As expected by their
      properties, DIM and FEN were weakly and moderately adsorbed to the soils,
      respectively. Soil OC seemed to be the major factor controlling FEN adsorption,
      whereas the mineral fraction played a key role in DIM adsorption, especially in
      RM1 with high clay:OC ratio. Although TWW did not significantly modify the
      adsorption of pesticides, it enhanced DIM desorption from the three soils.
      Adsorption of FEN to SV and RM3 was directly related to the concentration of DOC,
      possibly due to co-sorption phenomena. Hysteretic desorption was found in all
      cases, indicating partially reversible adsorption. While FEN desorption was not
      altered by the solutions, the use of sludge extracts at the highest DOC
      concentration (300 mg L-1) enhanced DIM desorption as occurred with TWW.
      Interactions with DOC in solution seemed to predominate for this less hydrophobic
      compound, thus increasing the risk of natural waters contamination if TWW will be
      used.

PMID- 29649732
TI  - Humic acid removal using cellulose acetate membranes grafted with poly (methyl
      methacrylate) and aminated using tetraethylenepentamine.
AB  - Graft copolymerization of cellulose acetate (CA) and poly (methyl methacrylate)
      (PMMA) was synthesized through free radical polymerization in the presence of
      cerium sulfate (CS) as initiator under nitrogen atmosphere in an aqueous
      solution. During the grafting reactions, the effects of polymerization time and
      temperature on the grafting were investigated. Furthermore, functionalization of
      the synthesized product was done using amine group (tetraethylenepentamine,
      TEPA). The results from Nuclear Magnetic Resonance (1H NMR) spectra confirmed a
      successful grafting of PMMA on the CA membrane surfaces. Zeta potential (zeta),
      field emission scanning electron microscopy (FESEM), and atomic absorption
      spectrophotometer (AAS) characterization studies were done. The maximum removal
      efficiencies for un-grafted CA (un-g-CA), CA-g-PMMA, and CA-g-PMMA-TEPA membranes
      at pH of 7.0 were 34.5%, 83.3%, and 99.1%, respectively. The removal percentage
      results were detected to increase with increasing in the regeneration cycles. At
      the end of the fourth cycle, the HA removal percentages were 41.6%, 87.4%, and
      99.9% for un-g-CA, CA-g-PMMA and CA-g-PMMA-TEPA membranes, respectively.

PMID- 29649733
TI  - Measuring water affordability in developed economies. The added value of a needs
      based approach.
AB  - In developed countries, water affordability problems remain up on the agenda as
      the increasing financial costs of water services can impede the realisation of an
      equal access to water. More than ever, public authorities that define water
      tariffs face the challenge of reconciling environmental and cost recovery
      objectives with equity and financial accessibility for all. Indicators of water
      affordability can be helpful in this regard. Conventional affordability
      indicators often rely on the actual amount that households spend on water use. In
      contrast, we propose a needs-based indicator that measures the risk of being
      unable to afford the amount of water necessary to fulfill essential needs, i.e.
      needs that should be fulfilled for adequate participation in society. In this
      paper we set forth the methodological choices inherent to constructing a needs
      based affordability indicator. Using a micro-dataset on households in Flanders
      (Belgium), we compare its results with the outcomes of a more common actual
      expenses-indicator. The paper illustrates how the constructed needs-based
      indicator can complement existing affordability indicators, and its capacity to
      reveal important risk groups.

PMID- 29649734
TI  - Production and application of O2 enriched air produced by fresh and salt water
      desorption in chemical plants.
AB  - Oxygen enriched air intensifies oxidation processes since smaller reactors reach
      the same conversion of typical unit operations that employ simple air as
      reactant. However, the cost to produce pure oxygen or oxygen enriched air with
      traditional methods, i.e. cryogenic separation or membrane technologies, may be
      unaffordable. Here, we propose a new continuous technology for gas mixture
      separation, focusing on the production of oxygen enriched air as a case study.
      This operation is an absorption-desorption process that takes advantage of the
      higher oxygen solubility in water compared to nitrogen. In a pressurized
      solubilisation tank, water absorbs air. Subsequently, reducing pressure desorbs
      oxygen enriched air. PRO/II 9.3 (Simsci-Scheider Electrics) simulated, optimized,
      and calculated the capital and operative expenses of this technology. Moreover,
      we tested for the first time salt water instead of distilled water as appealing
      possibility for chemical plant near sea and ocean. We varied the inlet water
      flowrate between 5 and 15 m3/h. The optimum operative absortion unit pressure is
      15-35 barg. After degassing, water may be recycled. With salt water, the
      extracted quantity of enriched air decreases compared with the desorption from
      fresh water (20% less), while the concentration of oxygen is independent from the
      salt concentration. The cost of enriched air at the optimum condition is 2-3.35
      EUR/Nm3.

PMID- 29649735
TI  - A review of analytical procedures for the simultaneous determination of medically
      important veterinary antibiotics in environmental water: Sample preparation,
      liquid chromatography, and mass spectrometry.
AB  - Medically important (MI) antibiotics are defined by the United States Food and
      Drug Administration as drugs containing certain active antimicrobial ingredients
      that are used for the treatment of human diseases or enteric pathogens causing
      food-borne diseases. The presence of MI antibiotic residues in environmental
      water is a major concern for both aquatic ecosystems and public health,
      particularly because of their potential to contribute to the development of
      antimicrobial-resistant microorganisms. In this article, we present a review of
      global trends in the sales of veterinary MI antibiotics and the analytical
      methodologies used for the simultaneous determination of antibiotic residues in
      environmental water. According to recently published government reports, sales
      volumes have increased steadily, despite many countries having adopted strategies
      for reducing the consumption of antibiotics. Global attention needs to be
      directed urgently at establishing new management strategies for reducing the use
      of MI antimicrobial products in the livestock industry. The development of
      standardized analytical methods for the detection of multiple residues is
      required to monitor and understand the fate of antibiotics in the environment.
      Simultaneous analyses of antibiotics have mostly been conducted using high
      performance liquid chromatography-tandem mass spectrometry with a solid-phase
      extraction (SPE) pretreatment step. Currently, on-line SPE protocols are used for
      the rapid and sensitive detection of antibiotics in water samples. On-line
      detection protocols must be established for the monitoring and screening of
      unknown metabolites and transformation products of antibiotics in environmental
      water.

PMID- 29649736
TI  - Impacts of biochar and oyster shells waste on the immobilization of arsenic in
      highly contaminated soils.
AB  - Soil contamination is a serious problem with deleterious impacts on global
      sustainability. Readily available, economic, and highly effective technologies
      are therefore urgently needed for the rehabilitation of contaminated sites. In
      this study, two readily available materials prepared from bio-wastes, namely
      biochar and oyster shell waste, were evaluated as soil amendments to immobilize
      arsenic in a highly As-contaminated soil (up to 15,000 mgAs/kg). Both biochar and
      oyster shell waste can effectively reduce arsenic leachability in acid soils.
      After application of the amendments (2-4% addition, w/w), the exchangeable
      arsenic fraction decreased from 105.8 to 54.0 mg/kg. The application of 2%biochar
      +2% oyster shell waste most effectively reduced As levels in the column leaching
      test by reducing the arsenic concentration in the porewater by 62.3% compared
      with the treatment without amendments. Biochar and oyster shell waste also
      reduced soluble As(III) from 374.9 +/- 18.8 MUg/L to 185.9 +/- 16.8 MUg/L and
      As(V) from 119.8 +/- 13.0 MUg/L to 56.4 +/- 2.6 MUg/L at a pH value of 4-5. The
      treatment using 4% (w/w) amendments did not result in sufficient As
      immobilization in highly contaminated soils; high soluble arsenic concentrations
      (upto193.0 MUg/L)were found in the soil leachate, particularly in the form of
      As(III), indicating a significant potential to pollute shallow groundwater
      aquifers. This study provides valuable insights into the use of cost-effective
      and readily available materials for soil remediation and investigates the
      mechanisms underlying arsenic immobilization in acidic soils.

PMID- 29649737
TI  - Modifications of protein-related compounds of beef minced meat treated by high
      pressure.
AB  - In this study, we evaluated the modifications of the protein-related compounds of
      minced beef treated with high pressure, including refrigeration after treatment.
      The free amino acid content, protein carbonyls and free thiol groups were
      assessed. High pressure up to 200 MPa had a significant effect. Above 300 MPa,
      irreversible structural changes occurred, with an increase in the protein
      oxidation products and a modification of the amounts of amino acids after 14 days
      of storage. Protein carbonyls and the free thiols were correlated with the free
      amino acids. These results showed that protein modifications under pressure
      result from both conformational and chemical changes, possibly associated with
      lipid changes under high-pressure treatment.

PMID- 29649738
TI  - Discovery of N-hydroxy-3-alkoxybenzamides as direct acid sphingomyelinase
      inhibitors using a ligand-based pharmacophore model.
AB  - Acid sphingomyelinase (ASM) has been shown to be involved in many physiological
      processes, emerging to be a promising drug target. In this study, we constructed
      a ligand-based pharmacophore model of ASM inhibitors and applied this model to
      optimize the lead compound alpha-mangostin, a known inhibitor of ASM. 23
      compounds were designed and evaluated in vitro for ASM inhibition, of these, 10
      compounds were found to be more potent than alpha-mangostin. This high hit ratio
      confirmed that the presented model is very effective and practical. The most
      potent hit, 1c, was found to selectively and competitively inhibit the enzyme and
      inhibit the generation of ceramide in a dose-dependent manner. Furthermore, 1c
      showed favorable anti-apoptosis and anti-inflammatory activity. Interactions with
      key residues and the Zn2+ cofactor of 1c were found by docking simulation. These
      results provide promising leads and important guidance for further development of
      efficient ASM inhibitors and drug candidates.

PMID- 29649739
TI  - Therapeutic journery of nitrogen mustard as alkylating anticancer agents:
      Historic to future perspectives.
AB  - Cancer is considered as one of the most serious health problems today. The
      discovery of nitrogen mustard as an alkylating agent in 1942, opened a new era in
      the cancer chemotherapy. This valuable class of alkylating agent exerts its
      biological activity by binding to DNA, cross linking two strands, preventing DNA
      replication and ultimate cell death. At the molecular level, nitrogen lone pairs
      of nitrogen mustard generate a strained intermediate "aziridinium ion" which is
      very reactive towards DNA of tumor cell as well as normal cell resulting in
      various adverse side effects alogwith therapeutic implications. Over the last 75
      years, due to its high reactivity and peripheral cytotoxicity, numerous
      modifications have been made in the area of nitrogen mustard to improve its
      efficacy as well as enhancing drug delivery specifically to tumor cells. This
      review mainly discusses the medicinal chemistry aspects in the development of
      various classes of nitrogen mustards (mechlorethamine, chlorambucil, melphalan,
      cyclophosphamide and steroidal based nitrogen mustards). The literature
      collection includes the historical and the latest developments in these areas.
      This comprehensive review also attempted to showcase the recent progress in the
      targeted delivery of nitrogen mustards that includes DNA directed nitrogen
      mustards, antibody directed enzyme prodrug therapy (ADEPT), gene directed enzyme
      prodrug therapy (GDEPT), nitrogen mustard activated by glutathione transferase,
      peptide based nitrogen mustards and CNS targeted nitrogen mustards.

PMID- 29649740
TI  - Design, synthesis, cytotoxicity and mechanism of novel dihydroartemisinin
      coumarin hybrids as potential anti-cancer agents.
AB  - To develop novel agents with anticancer activities, thirty-four new
      dihydroartemisinin-coumarin hybrids were designed and synthesized in this study.
      Those compounds were identified that had great anticancer activity against two
      cancer cell lines (MDA-MB-231 and HT-29). The structure-activity relationships of
      the derivatives were also discussed, and the results of docking analysis had
      shown that carbonic anhydrases IX (CA IX) was very likely to be one of the drug
      targets of the hybrids. Meanwhile, to clarify the mechanism of the anticancer
      activity of the hybrids molecule, we did further exploration in the bioactivity
      of the hybrids. The results had shown that these derivatives obviously inhibited
      proliferation of HT-29 cell lines, arrested G0/G1 phase of HT-29 cells,
      suppressed the migration of tumor cells, and induced a great decrease in
      mitochondrial membrane potential leading to apoptosis of cancer cells.
      Interestingly, the hybrids also induced the other cell death pathway-ferroptosis.

PMID- 29649741
TI  - Discovery of potent and selective BRD4 inhibitors capable of blocking TLR3
      induced acute airway inflammation.
AB  - A series of diverse small molecules have been designed and synthesized through
      structure-based drug design by taking advantage of fragment merging and
      elaboration approaches. Compounds ZL0420 (28) and ZL0454 (35) were identified as
      potent and selective BRD4 inhibitors with nanomolar binding affinities to
      bromodomains (BDs) of BRD4. Both of them can be well docked into the acetyl
      lysine (KAc) binding pocket of BRD4, forming key interactions including the
      critical hydrogen bonds with Asn140 directly and Tyr97 indirectly via a H2O
      molecule. Both compounds 28 and 35 exhibited submicromolar potency of inhibiting
      the TLR3-dependent innate immune gene program, including ISG54, ISG56, IL-8, and
      Grobeta genes in cultured human small airway epithelial cells (hSAECs). More
      importantly, they also demonstrated potent efficacy reducing airway inflammation
      in a mouse model with low toxicity, indicating a proof of concept that BRD4
      inhibitors may offer the therapeutic potential to block the viral-induced airway
      inflammation.

PMID- 29649742
TI  - Synthesis and structure-activity relationships of quinolinone and quinoline-based
      P2X7 receptor antagonists and their anti-sphere formation activities in
      glioblastoma cells.
AB  - Screening a compound library of quinolinone derivatives identified compound 11a
      as a new P2X7 receptor antagonist. To optimize its activity, we assessed
      structure-activity relationships (SAR) at three different positions, R1, R2 and
      R3, of the quinolinone scaffold. SAR analysis suggested that a carboxylic acid
      ethyl ester group at the R1 position, an adamantyl carboxamide group at R2 and a
      4-methoxy substitution at the R3 position are the best substituents for the
      antagonism of P2X7R activity. However, because most of the quinolinone
      derivatives showed low inhibitory effects in an IL-1beta ELISA assay, the core
      structure was further modified to a quinoline skeleton with chloride or
      substituted phenyl groups. The optimized antagonists with the quinoline scaffold
      included 2-chloro-5-adamantyl-quinoline derivative (16c) and 2-(4
      hydroxymethylphenyl)-5-adamantyl-quinoline derivative (17k), with IC50 values of
      4 and 3 nM, respectively. In contrast to the quinolinone derivatives, the
      antagonistic effects of the quinoline compounds (16c and 17k) were paralleled by
      their ability to inhibit the release of the pro-inflammatory cytokine, IL-1beta,
      from LPS/IFN-gamma/BzATP-stimulated THP-1 cells (IC50 of 7 and 12 nM,
      respectively). In addition, potent P2X7R antagonists significantly inhibited the
      sphere size of TS15-88 glioblastoma cells.

PMID- 29649745
TI  - Metabolomics-guided investigations of unintended effects of the expression of the
      hydroxycinnamoyl quinate hydroxycinnamoyltransferase (hqt1) gene from Cynara
      cardunculus var. scolymus in Nicotiana tabacum cell cultures.
AB  - Chlorogenic acids (CGAs) are phenolic compounds biosynthesized in the
      phenylpropanoid pathway, with hydroxycinnamoyl quinate
      hydroxycinnamoyltransferase (HQT) as the key enzyme. Variation of CGAs has been
      noted in different plants, with globe artichoke (Cynara cardunculus var. scolymus
      L.) producing high amounts and a diverse spectrum of CGAs in its leaves. In the
      current study, the effect of overexpression of the hqt1 transgene from globe
      artichoke in tobacco was evaluated at the metabolome level. Here, metabolomic
      approaches based on ultra-high performance liquid chromatography coupled to mass
      spectrometry, together with chemometric models such as principal component
      analysis and orthogonal partial least square discriminant analysis, were employed
      to evaluate altered metabolic changes due to hqt1 overexpression. CGA profiles
      (caffeoylquinic acids: 3-CQA, 4-CQA and 5-CQA; p-coumaroylquinic acids: 4-pCoQA
      and 5-pCoQA; and 4,5-di-caffeoylquinic acid) of transgenic tobacco cell cultures
      were detected at lower concentrations than in the wild type. Interestingly, the
      cells were found to rather accumulate, as an unintended effect, abscisic acid -
      and benzoic acid derivatives. The results suggest that insertion of hqt1 in
      tobacco, and overexpression in undifferentiated cells, led to rechannelling of
      the phenylpropanoid pathway to accumulate benzoic acids. These findings proved to
      be contrary to the results shown elsewhere in leaf tissues, thus indicating
      differential metabolic control and regulation in the undifferentiated cell
      culture system.

PMID- 29649744
TI  - Synthesis of 7beta-hydroxy-8-ketone opioid derivatives with antagonist activity
      at mu- and delta-opioid receptors.
AB  - Despite extensive years of research, the direct oxidation of the 7,8-double bond
      of opioids has so far received little attention and knowledge about the effects
      of this modification on activity at the different opioid receptors is scarce. We
      herein report that potassium permanganate supported on iron(II) sulfate
      heptahydrate can be used as a convenient oxidant in the one-step, heterogeneous
      conversion of Delta7,8-opioids to the corresponding 7beta-hydroxy-8-ketones.
      Details of the reaction mechanism are given and the effects of the substituent at
      position 6 of several opioids on the reaction outcome is discussed. The opioid
      hydroxy ketones prepared are antagonists at the mu- and delta-opioid receptors.
      Docking simulations and detailed structure-activity analysis revealed that the
      presence of the 7beta-hydroxy-8-ketone functionality in the prepared compounds
      can be used to gain activity towards the delta opioid receptor. The 7beta-hydroxy
      8-ketones prepared with this method can also be regarded as versatile
      intermediates for the synthesis of other opioids of interest.

PMID- 29649743
TI  - Recent advances in trimethoxyphenyl (TMP) based tubulin inhibitors targeting the
      colchicine binding site.
AB  - Microtubules (composed of alpha- and beta-tubulin heterodimers) play a pivotal
      role in mitosis and cell division, and are regarded as an excellent target for
      chemotherapeutic agents to treat cancer. There are four unique binding sites in
      tubulin to which taxanes, vinca alkaloids, laulimalide and colchicine bind
      respectively. While several tubulin inhibitors that bind to the taxane or vinca
      alkaloid binding sites have been approved by FDA, currently there are no FDA
      approved tubulin inhibitors targeting the colchicine binding site. Tubulin
      inhibitors that bind to the colchicine binding site have therapeutic advantages
      over taxanes and vinca alkaloids, for example, they can be administered orally,
      have less drug-drug interaction potential, and are less prone to develop multi
      drug resistance. Typically, tubulin inhibitors that bind to the colchicine
      binding site bear the trimethoxyphenyl (TMP) moiety which is essential for
      interaction with tubulin. Over the last decade, a variety of molecules bearing
      the TMP moiety have been designed and synthesized as tubulin inhibitors for
      cancer treatment. In this review, we focus on the TMP analogs that are designed
      based on CA-4, indole, chalcone, colchicine and natural product scaffolds which
      are known to interact with the colchicine binding site in tubulin. The challenges
      and future direction of the TMP based tubulin inhibitors are also discussed in
      detail.

PMID- 29649747
TI  - Polymeric micelles: Theranostic co-delivery system for poorly water-soluble drugs
      and contrast agents.
AB  - Interest in theranostic agents has continued to grow because of their promise for
      simultaneous cancer detection and therapy. A platform-based nanosized combination
      agent suitable for the enhanced diagnosis and treatment of cancer was prepared
      using polymeric polyethylene glycol-phosphatidylethanolamine-based micelles
      loaded with both, poorly soluble chemotherapeutic agent paclitaxel and
      hydrophobic superparamagnetic iron oxide nanoparticles (SPION), a Magnetic
      Resonance Imaging contrast agent. The co-loaded paclitaxel and SPION did not
      affect each other's functional properties in vitro. In vivo, the resulting
      paclitaxel-SPION-co-loaded PEG-PE micelles retained their Magnetic Resonance
      contrast properties and apoptotic activity in breast and melanoma tumor mouse
      models. Such theranostic systems are likely to play a significant role in the
      combined diagnosis and therapy that leads to a more personalized and effective
      form of treatment.

PMID- 29649746
TI  - Degradation of alpha-synuclein by dendritic cell factor 1 delays
      neurodegeneration and extends lifespan in Drosophila.
AB  - Parkinson's disease (PD) is a common neurodegenerative disease associated with
      the progressive loss of dopaminergic neurons in the substantia nigra.
      Proteinaceous depositions of alpha-synuclein (alpha-syn) and its mutations, A30P
      and A53T, are one important characteristic of PD. However, little is known about
      their aggregation and degradation mechanisms. Dendritic cell factor 1 (DCF1) is a
      membrane protein that plays important roles in nerve development in mouse. In
      this study, we aimed to show that DCF1 overexpression in a PD Drosophila model
      significantly ameliorates impaired locomotor behavior in third instar larvae and
      normalizes neuromuscular junction growth. Furthermore, climbing ability also
      significantly increased in adult PD Drosophila. More importantly, the lifespan
      dramatically extended by an average of approximately 23%, and surprisingly, DCF1
      could prevent alpha-syn-induced dopaminergic neuron loss by aggregating alpha-syn
      in the dorsomedial region of Drosophila. Mechanistically, we confirmed that DCF1
      could degrade alpha-syn both in vivo and in vitro. Our findings revealed an
      important role of DCF1 in PD process and may provide new potential strategies for
      developing drugs to treat neurodegenerative diseases.

PMID- 29649748
TI  - Rapid and selective sampling of IgG from skin in less than 1 min using a high
      surface area wearable immunoassay patch.
AB  - Microprojection array (MPA) patches are an attractive approach to selectively
      capture circulating proteins from the skin with minimal invasiveness for
      diagnostics at the point-of-care or in the home. A key challenge to develop this
      technology is to extract sufficient quantities of specific proteins from within
      the skin to enable high diagnostic sensitivity within a convenient amount of
      time. To achieve this, we investigated the effect of MPA geometry (i.e.
      projection density, length and array size) on protein capture. We hypothesised
      that the penetrated surface area of MPAs is a major determinant of protein
      capture however it was not known if simultaneously increasing projection density,
      length and array size is possible without adversely affecting penetration and/or
      tolerability. We show that increasing the projection density (5000-30,000 proj.
      cm-2) and array size (4-36 mm2) significantly increases biomarker capture whilst
      maintaining of a similar level tolerability, which supports previous literature
      for projection length (40-190 MUm). Ultimately, we designed a high surface area
      MPA (30,000 proj. cm-2, 36 mm2, 140 MUm) with a 4.5-fold increase in penetrated
      surface area compared to our standard MPA design (20,408 proj. cm-2, 16 mm2, 100
      MUm). The high surface area MPA captured antigen-specific IgG from mice in 30 s
      with 100% diagnostic sensitivity compared with 10-30 min for previous MPA
      immunoassay patches, which is over an order of magnitude reduction in wear time.
      This demonstrates for the first time that MPAs may be used for ultra-rapid (<1
      min) protein capture from skin in a time competitive with standard clinical
      procedures like the needle and lancet, which has broad implications for minimally
      invasive and point-of-care diagnostics.

PMID- 29649749
TI  - Ciprofloxacin and nalidixic acid resistance of Salmonella spp. isolated from
      retail food in Poland.
AB  - Distribution of amino acid substitutions in the quinolone resistance-determining
      region (QRDR) of gyrA, gyrB, parC, parE and determinants of plasmid-mediated
      quinolone resistance (PMQR) were investigated among quinolone-resistant
      Salmonella spp. strains isolated from retail food in Poland in the years 2008
      2013. Ten different amino acid substitutions were identified in QRDRs. Five
      different amino acid substitutions were identified in gyrA: Ser83Tyr, Ser83Phe,
      Asp87Tyr, Asp87Asn, Asp87Gly, two amino acid substitutions in parC: Thr57Ser,
      Ser80Ile and in parE: Leu445Phe, Arg511Ser. One substitution - Ser464Phe - was
      detected within gyrB. In gyrA a single substitution (Ser83Tyr) was identified the
      most frequently - 34.8% (63/181). Second most frequently identified variant
      (21.0%-38/181) was a co-existence of two single substitutions in gyrA: Ser83Tyr
      and parC: Thr57Ser. In four isolates co-existed three substitutions in three
      different genes: gyrA: Ser83Tyr + parC: Thr57Ser + parE: Leu445Phe (two
      isolates), gyrA: Ser83Phe + parC: Thr57Ser + parE: Leu445Phe, and gyrA: Ser83Tyr
      + parC: Thr57Ser + parE: Arg511Ser. In the two isolates four substitutions were
      identified - in gyrA: Ser83Phe + Asp87Tyr and in parC: Thr57Ser + Ser80Ile. Among
      resistant isolates, MIC values varied between 32 and 2048 mg/L (nalidixic acid)
      and between 0.125 and 16 mg/L (ciprofloxacin). MIC values of two isolates
      harboring qnrS1without any substitutions were 32 mg/L (NA) and 0.5-1.0 mg/L
      (CIP). The highest MIC values for NA and CIP were observed in two isolates of
      Salmonella spp. carrying double substitutions in gyrA: Ser83Phe + Asp87Tyr and
      parC: Thr57Ser + Ser80Ile. MIC value for NA was 2048 mg/L while for CIP - 16
      mg/L.

PMID- 29649750
TI  - Yersinia enterocolitica in a Brazilian pork production chain: Tracking of
      contamination routes, virulence and antimicrobial resistance.
AB  - This study aimed to track Yersinia enterocolitica contamination in a pork
      production chain in Minas Gerais, Brazil, and to characterize the virulence and
      antibiotic resistance of isolates. Samples were collected from four different
      steps of the pork production chain (pig farm, carcass, processing environment and
      end product; n = 870), and tested for the presence of Y. enterocolitica. The
      pathogen was detected in 8 samples (palatine tonsils = 5; mesenteric lymph nodes
      = 2; carcass after bleeding = 1), from which 16 isolates were obtained and
      identified as Y. enterocolitica bioserotype 4/O:3. XbaI macrorestriction allowed
      the clustering of isolates in 5 pulsetypes, and the identification of identical
      profiles of Y. enterocolitca isolated from different samples. All isolates were
      positive for the virulence related genes ail, virF, myfA, ystA, tccC, ymoA, hreP
      and sat, and negative for ystB, ystC, fepA, fepD and fes. Considering 17
      antibiotics from 11 classes, only ciprofloxacin and kanamycin were effective
      against all isolates, and three multidrug resistance profiles were identified
      among them, with simultaneous resistance to 9 of 11 classes. All isolates
      presented positive results for emrD, yfhD and marC, related to multidrug
      resistance. The results of this study demonstrated the contamination routes of Y.
      enterocolitica within the assessed pork production chain, and highlighted the
      pathogenic potential and antibiotic resistance of this foodborne pathogen.

PMID- 29649751
TI  - Orthogonal typing methods identify genetic diversity among Belgian Campylobacter
      jejuni strains isolated over a decade from poultry and cases of sporadic human
      illness.
AB  - Campylobacter jejuni is a zoonotic pathogen commonly associated with human
      gastroenteritis. Retail poultry meat is a major food-related transmission source
      of C. jejuni to humans. The present study investigated the genetic diversity,
      clonal relationship, and strain risk-analysis of 403 representative C. jejuni
      isolates from chicken broilers (n = 204) and sporadic cases of human diarrhea (n
      = 199) over a decade (2006-2015) in Belgium, using multilocus sequence typing
      (MLST), PCR binary typing (P-BIT), and identification of lipooligosaccharide
      (LOS) biosynthesis locus classes. A total of 123 distinct sequence types (STs),
      clustered in 28 clonal complexes (CCs) were assigned, including ten novel
      sequence types that were not previously documented in the international database.
      Sequence types ST-48, ST-21, ST-50, ST-45, ST-464, ST-2274, ST-572, ST-19, ST-257
      and ST-42 were the most prevalent. Clonal complex 21 was the main clonal complex
      in isolates from humans and chickens. Among observed STs, a total of 35 STs that
      represent 72.2% (291/403) of the isolates were identified in both chicken and
      human isolates confirming considerable epidemiological relatedness; these 35 STs
      also clustered together in the most prevalent CCs. A majority of the isolates
      harbored sialylated LOS loci associated with potential neuropathic outcomes in
      humans. Although the concordance between MLST and P-BIT, determined by the
      adjusted Rand and Wallace coefficients, showed low congruence between both typing
      methods. The discriminatory power of P-BIT and MLST was similar, with Simpson's
      diversity indexes of 0.978 and 0.975, respectively. Furthermore, P-BIT could
      provide additional epidemiological information that would provide further
      insights regarding the potential association to human health from each strain. In
      addition, certain clones could be linked to specific clinical symptoms. Indeed,
      LOS class E was associated with less severe infections. Moreover, ST-572 was
      significantly associated with clinical infections occurring after travelling
      abroad. Ultimately, the data generated from this study will help to better
      understand the molecular epidemiology of C. jejuni infection.

PMID- 29649752
TI  - Which donor is better when a matched donor is not available domestically?
      Comparison of outcomes of allogeneic stem cell transplantation with
      haploidentical and international donors in a homogenous ethnic population.
AB  - A substantial proportion of patients requiring allogeneic stem cell
      transplantation (alloSCT) do not have a human leukocyte antigen-matched sibling
      donor and need an alternative donor. In this multicenter retrospective study, we
      compared the outcomes of 176 patients with myelodysplastic syndrome and acute
      leukemia undergoing alloSCT from haploidentical (n = 121) and international (n =
      55) donors between 2002 and 2016. For recipients of haploidentical and
      international donors, the 2-year overall survival rates were 33.4% and 35.3%,
      respectively (P = 0.347), and relapse-free survival rates were 31.7% and 34.4% (P
      = 0.264), respectively. In addition, there were no significant differences in the
      cumulative incidences of acute and chronic graft versus host disease or
      incidences of infection within 30 days (all P > 0.05). Similarly, there were no
      significant differences in these measures for acute leukemia patients (n = 143;
      all P > 0.05). A multivariate analysis revealed that the donor type was not an
      independent prognostic or predictive factor. These data suggest that both
      haploidentical and international donors are feasible alternative sources for
      alloSCT when a matched donor is not available domestically.

PMID- 29649753
TI  - Fragmentation patterns involving ammonium adduct fragment ions: A comparison of
      the determination of metaldehyde in human blood by HPLC-QqQ-MS/MS and UHPLC-Q-TOF
      MS.
AB  - This paper presents a rapid, sensitive and precise method for the determination
      of metaldehyde in human blood, using ultra-performance liquid chromatography
      coupled with quadrupole time-of-flight tandem mass spectrometry and high
      performance liquid chromatography coupled with triple quadrupole tandem mass
      spectrometry. Separation was performed with a Poroshell 120 EC-C18 column; 2.7
      MUm atrazine-d5 (IS) and 200 mg NaCl were added to the blood sample. Proteins in
      human blood were precipitated using acetonitrile; the supernatant was then
      analyzed with the UHPLC-Q-TOF-MS or HPLC-QqQ-MS/MS system. The results of
      selectivity, linearity, accuracy, precision, limits of quantification, recovery,
      and matrix effects were sufficient to enable the measurement of metaldehyde in
      human blood samples. In addition, we proposed a fragmentation pathway involving
      ammonium adduct fragment ions for metaldehyde.

PMID- 29649754
TI  - A rapid method for sensitive profiling of bioactive triterpene and flavonoid from
      Astragalus mongholicus and Astragalus membranaceus by ultra-pressure liquid
      chromatography with tandem mass spectrometry.
AB  - Astragalus is one of the most popular Chinese herbal. Control of Astragalus
      quantity is most important, since that various varieties and ages largely affect
      bioactive metabolites and different pharmacological effects. Astragalus
      mongholicus and Astragalus membranaceus are both major sources of Astragalus
      according to the provisions in the Chinese Pharmacopoeia. Thus, a sensitive and
      rapid UPLC-MS/MS method for the simultaneous determination of l-Phenylalanine,
      Isoliquiritigenin, Liquiritigenin, Daidzein, Formononetin, Ononin, Calycosin,
      Calycosin-7-glucoside, Cycloastragenol, Astragaloside I, Astragaloside II,
      Astragaloside III and Astragaloside IV was established in this study. The
      detection was accomplished by MRM scanning in the positive ionization mode.
      Calibration curves offered linear ranges with r2 > 0.999. The method was
      successfully validated for the linearity, intra-day and inter day precisions,
      accuracy, recovery, matrix effect and stability. Then this method was
      successfully applied to detect the contents of 13 target flavonoids and
      triterpenoids metabolites in different organs and ages of A. mongholicus and A.
      membranaceus. Significant organs-, ages- and varieties- specificity of the 13
      target metabolites were observed and discussed. The results provided basis and
      support for further exploration of the distribution of bioactive metabolites,
      namely flavonoids and triterpenoids, in different organs and ages of two
      Astragalus varieties. This method should be applicable to various Astragalus
      matrices for the quantitative analysis of the target flavonoids and
      triterpenoids.

PMID- 29649755
TI  - Characterization of recombinant monoclonal antibody variants detected by
      hydrophobic interaction chromatography and imaged capillary isoelectric focusing
      electrophoresis.
AB  - In-depth characterization of the commonly observed variants is critical to the
      successful development of recombinant monoclonal antibody therapeutics. Multiple
      peaks of a recombinant monoclonal antibody were observed when analyzed by
      hydrophobic interaction chromatography and imaged capillary isoelectric focusing.
      The potential modification causing the heterogeneity was localized to F(ab')2
      region by analyzing the antibody after IdeS digestion using hydrophobic
      interaction chromatography. LC-MS analysis identified asparagine deamidation as
      the root cause of the observed multiple variants. While the isoelectric focusing
      method is expected to separate deamidated species, the similar profile observed
      in hydrophobic interaction chromatography indicates that the single site
      deamidation caused differences in hydrophobicity. Forced degradation demonstrated
      that the susceptible asparagine residue is highly exposed, which is expected as
      it is located in the light chain complementarity determining region. Deamidation
      of this single site decreased the mAb binding affinity to its specific antigen.

PMID- 29649757
TI  - Passive air sampling of flame retardants and plasticizers in Canadian homes using
      PDMS, XAD-coated PDMS and PUF samplers.
AB  - Passive air samplers (PAS) were evaluated for measuring indoor concentrations of
      phthalates, novel brominated flame retardants (N-BFRs), polybrominated diphenyl
      ethers (PBDEs), and organophosphate esters (OPEs). Sampling rates were obtained
      from a 50-day calibration study for two newly introduced PAS,
      polydimethylsiloxane (PDMS) or silicone rubber PAS (one with and one without a
      coating of styrene divinyl benzene co-polymer, XAD) and the commonly used
      polyurethane foam (PUF) PAS. Average sampling rates normalized to PAS surface
      area were 1.5 +/- 1.1 m3 day-1 dm-2 for both unsheltered PDMS and XAD-PDMS, and
      0.90 m3 +/- 0.6 day-1dm-2 for partially sheltered PUF. These values were derived
      based on the compound-specific sampling rates measured here and in the literature
      for the PAS tested, to reasonably account for site-specific variability of
      sampling rates. PDMS and PUF were co-deployed for three weeks in 51 homes located
      in Ottawa and Toronto, Canada. Duplicate PUF and PDMS samplers gave
      concentrations within 10% of each other. PDMS and PUF-derived air concentrations
      were not statistically different for gas-phase compounds. PUF had a higher
      detection of particle-phase compounds such as some OPEs. Phthalate and OPE air
      concentrations were ~100 times higher than those of N-BFRs and PBDEs.
      Concentrations were not systematically related to PM10, temperature or relative
      humidity. We conclude that both PAS provide replicable estimates of indoor
      concentrations of these targeted semi-volatile organic compounds (SVOCs) over a
      three-week deployment period. However, PUF is advantageous for collecting a wider
      range of compounds including those in the particle phase.

PMID- 29649756
TI  - Transcriptional effects of phospholipid fatty acid profile on rainbow trout liver
      cells exposed to methylmercury.
AB  - Lipids, and their constitutive fatty acids, are key nutrients for fish health as
      they provide energy, maintain cell structure, are precursors of signalling
      molecules and act as nuclear receptor ligands. These specific roles may be of
      crucial importance in a context of exposure to pollutants. We recently showed
      that the fatty acid profile of rainbow trout liver cell phospholipids modulates
      sensitivity to an acute methylmercury challenge. In order to investigate
      mechanisms of effects, we herein tested whether specific polyunsaturated fatty
      acids (PUFAs) may protect cells from methylmercury through decreasing
      intracellular mercury accumulation and/or enhancing cellular defences (e.g. via
      modulation of gene expression patterns). We also investigated the inverse
      relationship and assessed the impact of methylmercury on cellular fatty acid
      metabolism. To do so, the fatty acid composition of rainbow trout liver cell
      phospholipids was first modified by incubating them in a medium enriched in a
      specific PUFA from either the n-3 family (alpha-linolenic acid, ALA;
      eicosapentaenoic acid, EPA) or the n-6 family (linoleic acid, LA; arachidonic
      acid, AA). Cells were then exposed to methylmercury (0.15 or 0.50 MUM) for 24 h
      and sampled thereafter for assessing phospholipid fatty acid profile,
      intracellular total mercury burden, and expression pattern of genes involved in
      fatty acid metabolism, synthesis of PUFA-derived signalling molecules and stress
      response. We observed that cells incorporated the given PUFA and some
      biotransformation products in their phospholipids. Methylmercury had few impacts
      on this cellular phospholipid composition. None of the PUFA enrichments affected
      the cellular mercury burden, suggesting that the previously observed
      cytoprotection conferred by ALA and EPA was not linked to a global decrease in
      cellular accumulation of mercury. Fatty acid enrichments and methylmercury
      exposure both modulated gene expression patterns. Genes involved in the synthesis
      of PUFA-derived signalling molecules, in stress response and the orphan
      cytochrome P450 20A1 were identified as possible sites of interaction between
      fatty acids and methylmercury in rainbow trout liver cells.

PMID- 29649758
TI  - Association between nighttime artificial light pollution and sea turtle nest
      density along Florida coast: A geospatial study using VIIRS remote sensing data.
AB  - Artificial lighting at night has becoming a new type of pollution posing an
      important anthropogenic environmental pressure on organisms. The objective of
      this research was to examine the potential association between nighttime
      artificial light pollution and nest densities of the three main sea turtle
      species along Florida beaches, including green turtles, loggerheads, and
      leatherbacks. Sea turtle survey data was obtained from the "Florida Statewide
      Nesting Beach Survey program". We used the new generation of satellite sensor
      "Visible Infrared Imaging Radiometer Suite (VIIRS)" (version 1 D/N Band)
      nighttime annual average radiance composite image data. We defined light
      pollution as artificial light brightness greater than 10% of the natural sky
      brightness above 45 degrees  of elevation (>1.14 * 10-11 Wm-2sr-1). We fitted a
      generalized linear model (GLM), a GLM with eigenvectors spatial filtering (GLM
      ESF), and a generalized estimating equations (GEE) approach for each species to
      examine the potential correlation of nest density with light pollution. Our
      models are robust and reliable in terms of the ability to deal with data
      distribution and spatial autocorrelation (SA) issues violating model assumptions.
      All three models found that nest density is significantly negatively correlated
      with light pollution for each sea turtle species: the higher light pollution, the
      lower nest density. The two spatially extended models (GLM-ESF and GEE) show that
      light pollution influences nest density in a descending order from green turtles,
      to loggerheads, and then to leatherbacks. The research findings have an
      implication for sea turtle conservation policy and ordinance making. Near-coastal
      lights-out ordinances and other approaches to shield lights can protect sea
      turtles and their nests. The VIIRS DNB light data, having significant
      improvements over comparable data by its predecessor, the DMSP-OLS, shows promise
      for continued and improved research about ecological effects of artificial light
      pollution.

PMID- 29649759
TI  - Gene cloning, expression, and reducing property enhancement of nitrous oxide
      reductase from Alcaligenes denitrificans strain TB.
AB  - Nitrous oxide (N2O) is a potent greenhouse gas and tends to accumulate as an
      intermediate in the process of bacteria denitrification. To achieve complete
      reduction of nitrogen oxide (NOx) in bacteria denitrification, the structural
      gene nosZ encoding nitrous oxide reductase (N2OR) was cloned from Alcaligenes
      denitrificans strain TB (GenBank JQ044686). The recombinant plasmid containing
      the nosZ gene was built, and the expression of nosZ gene in Escherichia coli was
      determined. Results show that the nosZ gene consisting of 1917 nucleotides
      achieves heterologous expression successfully by codon optimization strategy
      under optimal conditions (pre-induction inoculum OD600 of 0.67, final IPTG
      concentration of 0.5 mM, inducing time of 6 h, and inducing temperature of 28 
      degrees C). Determination result of gas chromatography confirms that N2O
      degradation efficiency of recombinant E. coli is strengthened by at least 1.92
      times compared with that of original strain TB when treated with N2O as
      substrate. Moreover, N2OR activity in recombinant strain is 2.09 times higher
      than that in wild strain TB, which validates the aforementioned result and
      implies that the recombinant E. coli BL21 (DE3)-pET28b-nosZ is a potential
      candidate to control N2O accumulation and alleviate greenhouse effect. In
      addition, the N2OR structure and the possible N2O binding site in Alcaligenes sp.
      TB are predicted, which open an avenue for further research on the relationship
      between N2OR activity and its structure.

PMID- 29649760
TI  - Signalling cross-talk between nitric oxide and active oxygen in Trifolium repens
      L. plants responses to cadmium stress.
AB  - The significant influence of *NO on the stress response is well established;
      however, the precise metabolic pathways of *NO and RNS under metal stresses
      remain unclear. Here, the key components of ROS and RNS metabolism under Cd
      stress were investigated with multi-level approaches using high-quality forage
      white clover (Trifolium repens L.) plants. For the studied plants, Cd disturbed
      the redox homeostasis, affected the absorption of minerals, and exacerbated the
      degree of lipid peroxidation, thus triggering oxidative stress. However, *NO was
      also involved in regulating mineral absorption, ROS-scavenger levels and mRNA
      expression in Cd-treated white clover plants. In addition, GSNOR activity was up
      regulated by Cd with the simultaneous depletion of *NO generation and GSNO but
      was counteracted by the *NO donor sodium nitroprusside. Response to Cd-stressed
      SNOs was involved in generating ONOO- and NO2-Tyr in accordance with the
      regulation of *NO-mediated post-translational modifications in the ASC-GSH cycle,
      selected amino acids and NADPH-generating dehydrogenases, thereby provoking
      nitrosative stress. Taken together, our data provide comprehensive metabolite
      evidence that clearly confirms the relationships between ROS and RNS in Cd
      stressed plants, supporting their regulatory roles in response to nitro-oxidative
      stress and providing an in-depth understanding of the interaction between two
      families subjected to metal stresses.

PMID- 29649761
TI  - Seasonal trends in the composition and sources of PM2.5 and carbonaceous aerosol
      in Tehran, Iran.
AB  - Currently PM2.5 is a major air pollution concern in Tehran, Iran due to frequent
      high levels and possible adverse impacts. In this study, which is the first of
      its kind to take place in Tehran, composition and sources of PM2.5 and
      carbonaceous aerosol were determined, and their seasonal trends were studied. In
      this regard, fine PM samples were collected every six days at a residential
      station for one year and the chemical constituents including organic marker
      species, metals, and ions were analyzed by chemical analysis. The source
      apportionment was performed using organic molecular marker-based CMB receptor
      modeling. Carbonaceous compounds were the major contributors to fine particulate
      mass in Tehran, as OC and EC together comprised on average 29% of PM2.5 mass.
      Major portions of OC in Tehran were water insoluble and are mainly attributed to
      primary sources. Higher levels of several PAHs, which are organic tracers of
      incomplete combustion, and hopanes and steranes as organic tracers of mobile
      sources were obtained in cold months and compared to the warm months. The major
      contributing source to particulate OC was identified as vehicles, which
      contributed about 72% of measured OC. Among mobile sources, gasoline-fueled
      vehicles had the highest impact with a mean contribution of 48% to the measured
      OC. Mobile sources also were the largest contributor to total PM2.5 (40%),
      followed by dust (24%) and sulfate (11%). In addition to primary emissions,
      mobile sources also directly and indirectly played an important role in another
      27% of fine particulate mass (secondary organics and ions), which highlights the
      impact of vehicles in Tehran. Our results highlighted and quantified the role of
      motor vehicles in fine PM production, particularly during winter time. The
      results of this study could be used to set more effective regulations and control
      strategies particularly upon mobile sources.

PMID- 29649762
TI  - Airborne ultrafine particles in a naturally ventilated metro station: Dominant
      sources and mixing state determined by particle size distribution and volatility
      measurements.
AB  - Ultrafine particle number concentrations and size distributions were measured on
      the platform of a metro station in Athens, Greece, and compared with those
      recorded at an urban background station. The volatility of the sampled particles
      was measured in parallel, providing further insights on the mixing state and
      composition of the sampled particles. Particle concentration exhibited a mean
      value of 1.2 * 104 # cm-3 and showed a weak correlation with train passage
      frequency, but exhibited a strong correlation with urban background particle
      concentrations. The size distribution appears to be strongly influenced by
      outdoor conditions, such as the morning traffic rush hour and new particle
      formation events observed at noon. The aerosol in the metro was externally mixed
      throughout the day, with particle populations being identified (1) as fully
      refractory particles being more dominant during the morning traffic rush hours,
      (2) as core-shell structure particles having a non-volatile core coated with
      volatile material, and (3) fully volatile particles. The evolution of particle
      volatility and size throughout the day provide additional support that most
      nanoparticles in the metro station originate from outdoor urban air.

PMID- 29649763
TI  - Fluoride distribution and contamination in the water, soil and plants continuum
      and its remedial technologies, an Indian perspective- a review.
AB  - Fluorine is an essential element required in trace amounts but gets toxic for
      human beings at levels more than 1.5 mg F- L-1 primarily through drinking
      contaminated water. It is the 13th most abundant element and constitutes about
      0.06-0.09% in the earth crust. It is electronegative in aqueous medium forming
      fluoride ion (F-). Fluoride contamination in the environment occurs mostly due to
      anthropogenic and geogenic sources. Fluoride is widely distributed in all
      components of environment, air (0.1-0.6 MUg L-1) soils (150-400 mg Kg-1) rocks
      (100-2000 mg Kg-1), plant (0.01-42 mg Kg-1) and water (1.0-38.5 mg L-1). Human
      beings and animals are being exposed to F- primarily from water (0.2-42.0 mg L-1)
      and plants (0.77-29.5 MUg g-1). Fluorosis, a health hazard due to F- is a major
      problem in many countries across the world affecting about 200 million people
      globally. In India, > 62 million people in twenty states are facing problem due
      to F-. The most affected states are Rajasthan (7670 habitations), Telangana
      (1,174 habitations) and Karnataka (1122 habitations). To mitigate this problem,
      there is an urgent need to understand the current status and brief knowledge of F
      geochemistry. The objective of this review is to highlight different sources of
      F- that contaminate different environmental matrices including plants, the extent
      of contamination level in India, uptake, translocation and toxicity mechanism in
      plants. The review also highlights currently available mitigation methods or
      technologies through physio-chemical and biological means.

PMID- 29649764
TI  - Sleep after intranasal progesterone vs. zolpidem and placebo in postmenopausal
      women - A randomized, double-blind cross over study.
AB  - CONTEXT: The loss of progesterone during menopause is linked to sleep complaints
      of the affected women. Previously we demonstrated sleep promoting effects of oral
      progesterone replacement in postmenopausal women. The oral administration of
      progesterone, however, is compromised by individual differences in
      bioavailability and metabolism of the steroid. OBJECTIVE: We compared the sleep
      endocrine effects after intranasal progesterone (MPP22), zolpidem and placebo in
      healthy postmenopausal women. DESIGN: This was a randomized double-blind cross
      over study. SETTING: German monocentric study PARTICIPANTS: Participants were 12
      healthy postmenopausal women. INTERVENTIONS: Subjects received in randomized
      order four treatments, 2 doses of intranasal progesterone (4.5 mg and 9 mg of
      MPP22), 10 mg of zolpidem and placebo. OUTCOME MEASURES: Main outcome were
      conventional and quantitative sleep-EEG variables. Secondary outcomes were the
      subjective sleep variables and the sleep related concentrations of cortisol,
      growth hormone (GH), melatonin and progesterone. RESULTS: Sleep promoting effects
      were found after the higher dosage of MPP22 and after zolpidem. Zolpidem prompted
      benzodiazepine-like effects on quantitative sleep EEG as expected, whereas no
      such changes were found after the two dosages of MP22. Nocturnal progesterone
      levels increased after 9.0 mg MPP22. No other changes of hormone secretion were
      found. CONCLUSIONS: Our study shows sleep promoting effects after intranasal
      progesterone. The spectral signature of intranasal progesterone did not resemble
      the sleep-EEG alterations induced by GABA active compounds. Progesterone levels
      were elevated after 9.0 mg MPP22. No other endocrine effects were observed.

PMID- 29649766
TI  - microRNAs in the haemostatic system: More than witnesses of thromboembolic
      diseases?
AB  - MicroRNAs (miRNAs) are small endogenous RNAs that post-transcriptionally regulate
      gene expression. In the last few years, these molecules have been implicated in
      the regulation of haemostasis, and an increasing number of studies have
      investigated their relationship with the development of thrombosis. In this
      review, we discuss the latest developments regarding the role of miRNAs in the
      regulation of platelet function and secondary haemostasis. We also discuss the
      genetic and environmental factors that regulate miRNAs. Finally, we address the
      potential use of miRNAs as prognostic and diagnostic tools in thrombosis.

PMID- 29649767
TI  - Heparin-induced thrombocytopenia: A critical appraisal of clinical practice
      guidelines with the AGREE II instrument.
AB  - BACKGROUND: Despite the availability of clinical practice guidelines (CPGs), the
      risk of death or thromboembolic complication associated with heparin-induced
      thrombocytopenia (HIT) remains high. Our aim was to systematically review the
      quality of CPGs for HIT and summarize the recommendations. METHODS: CPGs for HIT
      were systematically searched on PubMed, Embase, guidelines' websites, and Google
      up to August 6, 2017. Independently, three appraisers assessed the quality of
      CPGs using the Appraisal of Guidelines for Research & Evaluation II (AGREE II)
      instrument and extracted the data. Recommendations were summarized, and a
      comparative study was conducted to analyze the consistency among guidelines.
      RESULTS: A total of 11 CPGs were evaluated. The quality assessed by AGREE II
      varied widely, not only between domains within guidelines, but also between
      guidelines across domains. The domain of scope and purpose and clarity of
      presentation obtained the highest median scores, while the domain of rigor of
      development and editorial independence obtained the lowest median scores. The
      ACCP guideline and BSH guideline were recommended for use in dealing with HIT,
      achieving a score of at least 50% in all six AGREE II domains. Recommendations
      across guidelines were inconsistent, especially in the choice of non-heparin
      anticoagulant for HIT. CONCLUSIONS: Future HIT guidelines should place more
      emphasis on methodological quality and improve efforts to include cost and local
      availability of drugs when providing recommendations.

PMID- 29649765
TI  - Probing the brain with molecular fMRI.
AB  - One of the greatest challenges of modern neuroscience is to incorporate our
      growing knowledge of molecular and cellular-scale physiology into integrated,
      organismic-scale models of brain function in behavior and cognition. Molecular
      level functional magnetic resonance imaging (molecular fMRI) is a new technology
      that can help bridge these scales by mapping defined microscopic phenomena over
      large, optically inaccessible regions of the living brain. In this review, we
      explain how MRI-detectable imaging probes can be used to sensitize noninvasive
      imaging to mechanistically significant components of neural processing. We
      discuss how a combination of innovative probe design, advanced imaging methods,
      and strategies for brain delivery can make molecular fMRI an increasingly
      successful approach for spatiotemporally resolved studies of diverse neural
      phenomena, perhaps eventually in people.

PMID- 29649768
TI  - The level of circulating fibroblast activation protein correlates with
      incorporation of alpha-2-antiplasmin into the fibrin clot.
AB  - INTRODUCTION: Circulating fibroblast activation protein (cFAP) cleaves alpha-2
      antiplasmin (alpha2AP) N-terminally, converting native Met-alpha2AP into Asn
      alpha2AP. Previous studies in purified model systems showed that Asn-alpha2AP is
      faster incorporated into a fibrin clot by activated factor XIII than Met
      alpha2AP, making the fibrin clot more resistant to fibrinolysis. The objective
      was to investigate whether cFAP level in plasma associated with the amount of
      alpha2AP incorporation into fibrin in a new plasma-based clotting assay.
      MATERIALS AND METHODS: We included 118 arterial thrombotic patients of the ATTAC
      study; 59 patients with diabetes mellitus (DM) and 59 age- and sex-matched
      patients without DM, additionally matched for type of arterial thrombosis
      (myocardial infarction or ischemic stroke). The percentage of alpha2AP
      incorporation was assessed with an alpha2AP incorporation assay mimicking
      physiological conditions with endogenous alpha2AP and physiological cFAP
      variation. cFAP levels were measured previously by ELISA. RESULTS: We found that
      on average 32.3 +/- 5.1% of alpha2AP was incorporated into fibrin, with slightly
      more alpha2AP incorporation in individuals with DM (33.3 +/- 4.9%) compared to
      individuals without DM (31.4 +/- 5.2%, p = 0.047), which validates our assay
      according to literature. The main finding of this study was that cFAP level
      positively correlated with alpha2AP incorporation into the fibrin clot (r =
      0.296, p = 0.001). CONCLUSION: The findings of a positive association between
      cFAP level and alpha2AP incorporation in a plasma-based system under
      physiological conditions support the hypothesis that N-terminal cleavage of
      alpha2AP leads to faster and more incorporation of alpha2AP into the fibrin clot,
      which may be clinically relevant.

PMID- 29649769
TI  - Sliding window averaging in normal and pathological motor unit action potential
      trains.
AB  - OBJECTIVE: To evaluate the performance of a recently proposed motor unit action
      potential (MUAP) averaging method based on a sliding window, and compare it with
      relevant published methods in normal and pathological muscles. METHODS: Three
      versions of the method (with different window lengths) were compared to three
      relevant published methods in terms of signal analysis-based merit figures and
      MUAP waveform parameters used in the clinical practice. 218 MUAP trains recorded
      from normal, myopathic, subacute neurogenic and chronic neurogenic muscles were
      analysed. Percentage scores of the cases in which the methods obtained the best
      performance or a performance not significantly worse than the best were computed.
      RESULTS: For signal processing figures of merit, the three versions of the new
      method performed better (with scores of 100, 86.6 and 66.7%) than the other three
      methods (66.7, 25 and 0%, respectively). In terms of MUAP waveform parameters,
      the new method also performed better (100, 95.8 and 91.7%) than the other methods
      (83.3, 37.5 and 25%). CONCLUSIONS: For the types of normal and pathological
      muscle studied, the sliding window approach extracted more accurate and reliable
      MUAP curves than other existing methods. SIGNIFICANCE: The new method can be of
      service in quantitative EMG.

PMID- 29649770
TI  - Advanced dynamic statistical parametric mapping with MEG in localizing
      epileptogenicity of the bottom of sulcus dysplasia.
AB  - OBJECTIVE: To investigate whether advanced dynamic statistical parametric mapping
      (AdSPM) using magnetoencephalography (MEG) can better localize focal cortical
      dysplasia at bottom of sulcus (FCDB). METHODS: We analyzed 15 children with
      diagnosis of FCDB in surgical specimen and 3 T MRI by using MEG. Using AdSPM, we
      analyzed a +/-50 ms epoch relative to each single moving dipole (SMD) and applied
      summation technique to estimate the source activity. The most active area in
      AdSPM was defined as the location of AdSPM spike source. We compared spatial
      congruence between MRI-visible FCDB and (1) dipole cluster in SMD method; and (2)
      AdSPM spike source. RESULTS: AdSPM localized FCDB in 12 (80%) of 15 children
      whereas dipole cluster localized six (40%). AdSPM spike source was concordant
      within seizure onset zone in nine (82%) of 11 children with intracranial video
      EEG. Eleven children with resective surgery achieved seizure freedom with follow
      up period of 1.9 +/- 1.5 years. Ten (91%) of them had an AdSPM spike source in
      the resection area. CONCLUSION: AdSPM can noninvasively and neurophysiologically
      localize epileptogenic FCDB, whether it overlaps with the dipole cluster or not.
      SIGNIFICANCE: This is the first study to localize epileptogenic FCDB using MEG.

PMID- 29649771
TI  - Systematic forensic toxicological analysis by liquid-chromatography-quadrupole
      time-of-flight mass spectrometry in serum and comparison to gas chromatography
      mass spectrometry.
AB  - Comprehensive screening procedures for psychoactive agents in body fluids are an
      essential task in clinical and forensic toxicology. With the continuous emergence
      and adaption of new psychoactive substances (NPS) keeping a screening method up
      to date is challenging. To meet these demands, hyphenated high-resolution mass
      spectrometry has gained interest as extensive and expandable screening approach.
      Here we present a comprehensive method for systematic toxicological analysis of
      serum by liquid chromatography-quadrupole-time-of-flight mass spectrometry (LC
      QTOF-MS) with data independent acquisition. The potential of this method was
      demonstrated by analysis of 247 authentic serum- and 12 post-mortem femoral blood
      samples. Thus 950 compounds, comprising 185 different drugs and metabolites could
      be identified. For the detected substances, including pharmaceutical substances,
      illicit drugs as well as NPS, serum concentrations were confirmed ranging from
      traces to toxic values indicating the capability for forensic toxicological
      requirements. Positive identification of drugs was achieved by accurate mass
      measurement (+/-5ppm for [M+H]+; +/-10ppm for [M-H]-), retention time (+/
      0.35min), isotopic pattern match (less than 10 m/z RMS [ppm]), isotope match
      intensity (less than 20% RMS) and the presence of at least two fragment ions. The
      LC-QTOF-MS procedure was shown to be superior to serum screening by GC-MS, since
      240% (335 versus 141) more drugs were identified in serum samples compared to GC
      MS.

PMID- 29649772
TI  - Enhancement of Th1 immune response against Leishmania cysteine peptidase A, B by
      PLGA nanoparticle.
AB  - Recombinant cysteine peptidase vaccine can induce protective immunity against
      cutaneous leishmaniasis. However, the antigenic diversity and variable
      immunogenicity prevents them from being approved for general vaccination.
      Different approaches like adjuvant application and antigen delivery systems are
      studied to increase their efficacy. Nanoparticles can both stimulated antigen
      uptakes and affect direction of immune response. In this study the effect of PLGA
      nanoparticles were considered to enhance the immune response against recombinant
      CPA (CPA) and CPB (CPB). For this purpose, L. major CPA and CPB were prepared.
      PLGA were conjugated to the proteins using Aldehyde/Hydrazine Reaction.
      Conjugation efficacy and created nanoparticle morphology were determined by FTIR
      and SEM methods, respectively. BALB/c mice were received intraperitoneally three
      boosts of 7 MUg/mouse of each antigen alone (CPA/CPB/CPA + CPB) or as PLGA
      conjugated form in different Study groups, at 3 weeks interval. After
      vaccination, mice were challenged with 106L. major, subcutaneously. Time course
      study of lesion development demonstrated nanoparticle efficacy in parasite
      dissemination control that confirmed by spleen parasite burden assay. Significant
      induction of nitric oxide production by peritoneal macrophages and increase in
      splenocyte IFN-gamma production showed the protective effect of PLGA-CPA/CPB
      vaccination in comparison to CPA and CPB alone. Current study demonstrated that
      the conjugation of the antigen with the PLGA can activate immune responses
      against L. major. However, further study is necessary to assess the long-term
      effect and other aspects of immune response.

PMID- 29649773
TI  - Optimization study of direct morphology observation by cold field emission SEM
      without gold coating.
AB  - Gold coating is a general operation that is generally applied on non-conductive
      or low conductive materials, during which the morphology of the materials can be
      examined by scanning electron microscopy (SEM). However, fatal deficiencies in
      the materials can result in irreversible distortion and damage. The present study
      directly characterized different low conductive materials such as hydroxyapatite,
      modified poly(vinylidene fluoride) (PVDF) fiber, and zinc oxide nanopillar by
      cold field emission scanning electron microscopy (FE-SEM) without a gold coating.
      According to the characteristics of the low conductive materials, various test
      conditions, such as different working signal modes, accelerating voltages,
      electron beam spots, and working distances, were characterized to determine the
      best morphological observations of each sample.

PMID- 29649775
TI  - Emerging issues in the environmental context of antibiotic-resistance.

PMID- 29649774
TI  - Effectiveness of National Weather Service heat alerts in preventing mortality in
      20 US cities.
AB  - BACKGROUND: Extreme heat is a well-documented public health threat. The US
      National Weather Service (NWS) issues heat advisories and warnings (collectively,
      "heat alerts") in advance of forecast extreme heat events. The effectiveness of
      these alerts in preventing deaths remains largely unknown. OBJECTIVES: To
      quantify the change in mortality rates associated with heat alerts in 20 US
      cities between 2001 and 2006. METHODS: Because NWS heat alerts are issued based
      on forecast weather and these forecasts are imperfect, in any given location
      there exists a set of days of similar observed heat index in which heat alerts
      have been issued for some days but not others. We used a case-crossover design
      and conditional logistic regression to compare mortality rates on days with
      versus without heat alerts among such eligible days, adjusting for maximum daily
      heat index and temporal factors. We combined city-specific estimates into a
      summary measure using standard random-effects meta-analytic techniques. RESULTS:
      Overall, NWS heat alerts were not associated with lower mortality rates (percent
      change in rate: -0.5% [95% CI: -2.8, 1.9]). In Philadelphia, heat alerts were
      associated with a 4.4% (95% CI: -8.3, -0.3) lower mortality rate or an estimated
      45.1 (95% empirical CI: 3.1, 84.1) deaths averted per year if this association is
      assumed to be causal. No statistically significant beneficial association was
      observed in other individual cities. CONCLUSIONS: Our results suggest that
      between 2001 and 2006, NWS heat alerts were not associated with lower mortality
      in most cities studied, potentially missing a valuable opportunity to avert a
      substantial number of heat-related deaths. These results highlight the need to
      better link alerts to effective communication and intervention strategies to
      reduce heat-related mortality.

PMID- 29649776
TI  - Occurrence of 44 elements in human cord blood and their association with growth
      indicators in newborns.
AB  - There is growing concern about environmental pollution produced by elements,
      including "emerging" contaminants, such as rare earth elements (REE) and other
      trace elements (TE), which are extensively and increasingly employed in the
      manufacture of consumer electronics. Previous research has shown that prenatal
      exposure to some elements (mainly heavy metals) may be associated with decreased
      fetal growth and other adverse birth outcomes. Recent studies have also shown
      that environmental exposure to REE and TE may be related to adverse effects on
      human health. This cross-sectional study, which included nearly 92% of the births
      in 2016 in La Palma (Canary Islands, Spain; n = 471), aimed to evaluate the
      potential adverse health effects exerted by a wide range of elements on newborns.
      We quantified the levels of 44 elements (including 26 REE and TE) in their
      umbilical cord blood. Our results showed low or very low levels of most elements.
      We found an inverse association between antimony (Sb) and birth weight
      (Spearman's r = -0.106, p = 0.021). A similar trend was observed between nickel
      (Ni) and birth weight and between chromium (Cr) and birth length, although in
      this case the significance was borderline. Bismuth appeared as a risk factor for
      having a birth weight below the tenth percentile in the univariate (OR = 3.30;
      95% CI = 1.25-8.78; p = 0.017) and multivariate analyses (OR = 5.20; 95% CI =
      1.29-20.91; p = 0.020). When assessing the effect of element mixtures, the sum of
      Cr, Ni, and Sb appeared as a risk factor for having a birth weight below the
      tenth percentile in the univariate (OR = 2.41; 95% CI = 1.08-5.35; p = 0.031) and
      multivariate analyses (OR = 3.84; 95% CI = 1.42-10.39; p = 0.008). Our findings
      suggest that some inorganic elements-isolated or in mixture-are associated to a
      lower fetal growth. Additional research is needed to understand the role of
      inorganic pollutants on fetal development.

PMID- 29649777
TI  - Eyes of the Deep-sea Floor: The Integrative Taxonomy of the Foraminiferal Genus
      Vanhoeffenella.
AB  - Vanhoeffenella is a common deep-sea monothalamous foraminifer, some species of
      which have a unique eye-like test morphology. Owing to its world-wide
      distribution, it has been recorded numerous times since the "heroic age" of the
      deep-sea exploration in the early 20th century. So far, only 4 species have been
      described, and no attempts have been made to estimate the real diversity of this
      peculiar genus. Over the last fifteen years, we have collected specimens of
      Vanhoeffenella from various deep-sea areas, providing the basis for an
      integrative taxonomy and biogeography of this genus. Here, we clarify the
      phylogenetic position of Vanhoeffenella and give an account of its diversity in
      the Atlantic, Arctic and Southern Oceans (the Weddell Sea) as revealed by genetic
      marker (SSU rDNA) and morphology. Our study shows that Vanhoeffenella branches
      within Clade F of monothalamids and incorporates at least 10 putative species.
      Some could be distinguished by either morphological or molecular features, but
      only the integrative taxonomic approach provides a robust way to assess their
      diversity. We examine the new material of the type species (V. gaussi Rhumbler),
      redescribe the poorly-known V. oculus Earland and describe formally a fifth
      species, V. dilatata sp. nov.

PMID- 29649778
TI  - In silico design of small peptides antagonist against leptin receptor for the
      treatment of obesity and its associated immune-mediated diseases.
AB  - Excess adiposity in obese inhibits negatively impacts immune function and host
      defence. Obesity is characterized by a state of low-grade, chronic inflammation
      in addition to disturbed levels of circulating nutrients and metabolic hormones.
      The impact of metabolic abnormalities on obesity-related co-morbidities has
      undergone intense scrutiny over the past decades. Thus, treatment of obesity and
      its associated immune-mediated diseases is challenging due to impaired function
      of leptin system. These disorders are managed through antibiotics and by
      cytokines replacement. However, the effectiveness of cytokines coupled to the
      complexity of the cytokine network leads to severe side-effects, which can still
      occur after careful preclinical evaluation. In addition, synthetic
      immunotherapeutics carry a degree of risk, time-consuming and expensive. Hence,
      the complexity of existing therapy and adverse effects emphasizes the need for an
      alternative approach for the management of immune dysfunction associated with
      obesity. Computer-aided small molecule antibody technology has been successful in
      the design of novel biologicals for the diagnosis of diseases and therapeutic
      interventions. In this study, the crystal structure of leptin receptor (LEPR)
      complex with monoclonal antibody (9F8 Fab) was explored to predict Ag-Ab
      interactions using bioinformatics tools. The LEPR of complementarity-determining
      region (CDR) loops were mutated with published positive control residues of Ser,
      Thr, Tyr, Trp, and Phe to design a set of 678 peptides which were evaluated
      through Ag-peptide docking, binding free-energies, and interaction energies.
      Thus, hypothesized novel peptides can be explored as clinically applicable
      antagonists for the treatment of obesity and associated immune-mediated diseases.

PMID- 29649780
TI  - Smoking and local unemployment: Evidence from Germany.
AB  - In this paper, we use data from the German Socio-Economic Panel to investigate
      the effect of macro-economic conditions (in the form of local unemployment rates)
      on smoking behavior. The results from our panel data models, several of which
      control for selection bias, indicate that the propensity to become a smoker
      increases significantly during an economic downturn, with an approximately 0.7
      percentage point increase for each percentage point rise in the unemployment
      rate. Conversely, conditional on the individual being a smoker, cigarette
      consumption decreases with rising unemployment rates, with a one percentage point
      increase in the regional unemployment rate leading to a decrease in consumption
      up to 0.8 percent.

PMID- 29649779
TI  - Activation of Hepatic Stellate Cells During Liver Carcinogenesis Requires
      Fibrinogen/Integrin alphavbeta5 in Zebrafish.
AB  - Hepatocellular carcinoma (HCC) is one of the most common cancers and it usually
      develops from a background of liver fibrosis or inflammation. The crosstalk
      between tumor cells and stromal cells plays an important and stimulating role
      during tumor progression. Previously we found in a krasV12-induced zebrafish HCC
      model that oncogenic hepatocytes activate hepatic stellate cells (HSCs) by up
      regulation of serotonin and activate neutrophils and macrophages by up-regulation
      of cortisol. In the present study, we found a novel signaling transduction
      mechanism between oncogenic hepatocytes and HSCs. After krasV12 induction,
      fibrinogen was up-regulated in oncogenic hepatocytes. We reasoned that fibrinogen
      may bind to integrin alphavbeta5 on HSCs to activate HSCs. Consistent with this
      notion, pharmaceutical treatment using an antagonist of integrin alphavbeta5,
      cilengitide, significantly blocked HSC activation and function, accompanied by
      attenuated proliferation of oncogenic hepatocytes and progression of liver
      fibrosis. On the contrary, adenosine 5'-diphosphate, an agonist of alphavbeta5,
      activated HSCs significantly that further stimulated the tumor progression and
      liver fibrosis. Interestingly, in human liver disease samples, we detected an
      increased level of fibrinogen during tumor progression which indicated the
      potential role of fibrinogen signaling in HCC progression. Thus, we concluded a
      novel interaction between oncogenic hepatocytes and HSCs through the fibrinogen
      related pathway in both the zebrafish HCC model and human liver disease samples.

PMID- 29649781
TI  - Persisting patterns of human height? Regional differences in living standards in
      the Early Middle Ages.
AB  - oProximity to protein production' has recently been identified as an important
      determinant of regional variation of biological standards of living, as evidenced
      by average heights. The number of cows per person turned out to be a useful proxy
      where milk consumption had not been documented. Re-analyses of agricultural
      production and average male heights in early 19th-century central Europe show
      that indicators of agricultural suitability and potential for food production
      constructed from modern agro-ecological data are strongly correlated with
      historical agricultural specialisation. This paper uses a dataset of estimated
      heights and evidence on circumstances of the burial of about 2200 individuals who
      had lived in southwestern Germany during the 5th-8th centuries to assess the
      usefulness of modern proxy variables for explanations of regional differences in
      living standards in the distant past. Assuming some continuity in the relative
      suitability of smaller areas, the results suggest similar responses to
      environmental and climatic constraints, even though population density,
      agricultural technology, market integration, and consumption patterns of
      subsistence farming were very different from 19th-century conditions.

PMID- 29649782
TI  - Balloon pulmonary angioplasty in a patient with prostate cancer and chronic
      thromboembolic pulmonary hypertension.
AB  - Chronic thromboembolic pulmonary hypertension (CTEPH) is a subtype of pulmonary
      hypertension characterized by a mean pulmonary artery pressure >=25 mm Hg due to
      obstructive fibrotic thromboembolic material in the pulmonary arteries.
      Malignancy is a significant risk for developing CTEPH. The option for inoperable
      CTEPH is largely medical with variable outcomes. Balloon pulmonary angioplasty
      (BPA) is a promising option for inoperable patients given distal-type CTEPH, co
      morbidities, or residual pulmonary hypertension after surgery. We present a case
      of a patient with prostate cancer and CTEPH successfully treated with balloon
      pulmonary angioplasty.

PMID- 29649784
TI  - Bacterial communities of four adjacent fresh lakes at different trophic status.
AB  - Knowing the microbial compositions in fresh lakes is significant to explore the
      mechanisms of eutrophication and algal blooms. This study reported on the
      bacterial communities of the four adjacent fresh lakes at different trophic
      status by Illumina MiSeq Platform, which were Tangxun Lake (J1), Qingling Lake
      (J2), Huangjia Lake (J3) and Niushan Lake (J4) in Wuhan, China. J1 had the
      highest salinity and phosphorus. J2 was abundant in TC (Total Carbon)/TOC (Total
      Organic Carbon.), calcium and magnesium. J3 had the highest content of nitrogen,
      iron and pollution of heavy metals. High-throughput sequencing analysis of the
      16S rRNA gene revealed that the eutrophic lakes (J1, J2 and J3) were dominated by
      Cyanobacteria (46.1% for J1, 40.8% for J2, 33.4% for J3) and the oligotrophic
      lake (J4) was dominated by Actinobacteria (34.2%). An increase of Cyanobacteria
      could inhibit the growth of Proteobacteria, Actinobacteria and Bacteroidetes.
      Functional inferences from 16S rRNA sequences suggested that J4 had more abundant
      bacteria with regard to substrate metabolism than J1, J2, and J3. Burkholderia
      and Fluviicola might be a suggestion of good water quality. The results
      demonstrated that the bacterial community could well reflect the water quality of
      the four lakes.

PMID- 29649783
TI  - Radiation dose reduction in perfusion CT imaging of the brain using a 256-slice
      CT: 80 mAs versus 160 mAs.
AB  - PURPOSE: To examine CTP of the brain in real patient data after reducing tube
      current down to 80 mAs to decrease radiation dose. METHODS: CTP was acquired in
      60 suspected stroke patients with 80 (n: 30) or 160 (n: 30) mAs. Data were
      analyzed retrospectively by two independent readers. SNR, perfusion maps and
      image quality were compared in hypoperfused and non-affected areas. RESULTS: SNR
      was significantly higher in CTP with 160 mAs compared to 80 mAs (p < 0.001) in
      non-affected regions, but there was no significant difference in hypoperfused
      regions. Overall, images with 80 mAs were rated worse than the ones with 160 mAs
      (3.0 +/- 0.7 versus 4.0 +/- 0.7), however, still as sufficient to detect proximal
      vessel occlusions. CONCLUSION: Tube current of 80 mAs is still sufficient for the
      detection of perfusion deficits of proximal vessel occlusions.

PMID- 29649785
TI  - Albumin biofunctionalization to minimize the Staphylococcus aureus adhesion on
      solid substrates.
AB  - Staphylococcus aureus has become the most common opportunistic microorganism
      related to nosocomial infections due to the bacteria capacity to form biofilms on
      biomedical devices and implants. Since bacterial adhesion is the first step in
      this pathogenesis, it is evident that inhibiting such a process will reduce the
      opportunity for bacterial colonization on the devices. This work is aimed at
      optimizing a surface biofunctionalization strategy to inhibit the adhesion of S.
      aureus on solid substrates. The first part of the work deals with the albumin
      adsorption-desorption process, studied by a factorial design of experiments to
      explore a wide range of experimental factors (protein concentration, pH, flow
      rate and adsorption time) and responses (initial adsorption rate, adsorbed
      amount, desorbed extent) for hydrophilic and hydrophobic substrates, with a
      reduced number of experiments. This approach allows the simultaneous evaluation
      of the factors affecting the albumin adsorption-desorption process to find a
      qualitative correlation with the amount of alive S. aureus adhered on albumin
      biofunctionalized substrates. The results of this work point to a relationship
      between bacterial adhesion and the degree of albumin relaxation on the solid
      substrate. In fact, the inhibition of bacterial adhesion on albumin
      biofunctionalized substrates is due to the surface perturbation on the native
      structure of the protein. On this base, a biofunctionalization strategy was
      designed using a solution of thermally treated albumin molecules (higher beta
      sheet or unordered secondary structure elements) to biofunctionalize solid
      substrates by dipping. With these albumin biofunctionalized substrates S. aureus
      adhesion was minimized.

PMID- 29649786
TI  - Nanoemulsions and topical creams for the safe and effective delivery of
      lipophilic antioxidant coenzyme Q10.
AB  - Emulsion-based delivery systems have been developed to increase the topical
      bioavailability of lipophilic active compounds within skin membrane. The aim was
      to develop nanoemulsion from natural sources (rapeseed oil) with the same sources
      of pure phospholipids (lecithin) rich on mono and polyunsaturated fatty acids for
      encapsulation of hydrophobic antioxidant (Coenzyme Q10) giving nanoemulsion with
      double functionality. Nanoemulsions were used for cream preparation using xanthan
      gum and carboxylmethylcellulose as texturizing agents. The physico-chemical
      properties, toxicity and biocompatibility were evaluated. Physical stability was
      followed under different storage temperatures (25; 37 and 50  degrees C) for one
      month and revealed stable systems with 150 nm particle size. Anionic thickening
      addition influenced the electrophoretic mobility but not the size distribution.
      The addition of polyanionic thickening in nanoemulsions promoted negative surface
      charge that increased electrostatic repulsive forces between droplets avoiding
      destabilization phenomena such as coalescence and Ostwald ripening. Moreover,
      chemical stability evaluation of components confirmed the absence of
      interactions. FTIR analysis indicated the vibration band position of cis double
      stretching of unsaturated fatty acids between 3009 and 3006 cm-1, which
      characterized the non-oxidized oils with same intensities before and after
      sonication. Antioxidants measurement shown that CMC significantly reduced
      antioxidant activity due to masking action of CoQ10 functional groups by the
      carboxylmethylcellulose gum conversely to xanthan gum addition. Finally, in vitro
      biocompatibility results shown that CoQ10 protected the DNA, and xanthan gum
      improve glucose metabolism inducing a better cell growth, while
      carboxymethylcellulose which was not metabolized by fibroblast cell inducing
      lower growth rate.

PMID- 29649788
TI  - LC-MS/MS method for the simultaneous quantification of intestinal CYP and UGT
      activity.
AB  - Many orally administered drugs are subject to first-pass metabolism by cytochrome
      P450 (CYP) enzymes and uridine 5'-diphospho-glucuronosyltransferases (UGT). While
      their hepatic activity is well characterized, respective information about the
      intestine are very scare due to limited availability of tissue, very low
      microsomal protein content and the heterogeneity of the individual segments. As a
      consequence, determination of enzyme kinetic parameters is challenging. It was
      therefore the aim of this study to develop a sensitive liquid chromatography
      tandem mass spectrometry method for the simultaneous quantification of CYP and
      UGT metabolites formed by clinically relevant intestinal biotransformation
      enzymes: 4-hydroxydiclofenac (CYP2C9), 5-hydroxyomeprazole (CYP2C19), dextrorphan
      (CYP2D6), 1-hydroxymidazolam (CYP3A), ezetimibe glucuronide (UGT1A) and naloxone
      glucuronide (UGT2B7). After precipitation of microsomal protein with
      acetonitrile, analytes were chromatographically separated on a C18 column with
      gradient elution using acetonitrile and water, both containing 0.1% formic acid
      and detected with a tandem mass spectrometer operating in positive mode with
      electron spray ionization. The assay was validated according to current
      bioanalytical guidelines regarding linearity, accuracy, precision, stability,
      recovery and matrix effects spanning an analytical range from 1 to 200 nmol/L for
      each analyte. The developed method was successfully applied to a proof of concept
      experiment using pooled human jejunal microsomes (50 MUg protein/mL) in order to
      determine enzyme kinetic parameters. Formation of all monitored metabolites
      followed Michaelis-Menten kinetics and allowed calculation of KM and Vmax values.
      The developed method may be useful for characterization of enzymatic activity in
      the human intestine which may allow more precise insights into the intestinal
      contribution to first pass metabolism of drugs.

PMID- 29649787
TI  - Defective protein repair under methionine sulfoxide A deletion drives autophagy
      and ARE-dependent gene transcription.
AB  - OBJECTIVE: Reduction of oxidized methionines is emerging as a major protein
      repair pathway. The lack of methionine sulfoxide reductase A (MsrA) exacerbates
      cardiovascular disease phenotypes driven by increased oxidative stress. However,
      the role of MsrA on maintaining cellular homeostasis in the absence of excessive
      oxidative stress is less well understood. METHODS AND RESULTS: Constitutive
      genetic deletion of MsrA increased formation of p62-containing protein
      aggregates, activated autophagy, and decreased a marker of apoptosis in vascular
      smooth muscle cells (VSMC). The association of Keap1 with p62 was augmented in
      MsrA-/- VSMC. Keap1 targets the transcription factor Nrf2, which regulates
      antioxidant genes, for proteasomal degradation. However, in MsrA-/- VSMC, the
      association of Nrf2 with Keap1 was diminished. Whereas Nrf2 mRNA levels were not
      decreased in MsrA-/- VSMC, we detected decreased ubiquitination of Nrf2 and a
      corresponding increase in total Nrf2 protein in the absence of biochemical
      markers of oxidative stress. Moreover, nuclear-localized Nrf2 was increased under
      MsrA deficiency, resulting in upregulation of Nrf2-dependent transcriptional
      activity. Consequently, transcription, protein levels and enzymatic activity of
      glutamate-cysteine ligase and glutathione reductase were greatly augmented in
      MsrA-/- VSMC. SUMMARY: Our findings demonstrate that reversal of methionine
      oxidation is required for maintenance of cellular homeostasis in the absence of
      increased oxidative stress. These data provide the first link between autophagy
      and activation of Nrf2 in the setting of MsrA deletion.

PMID- 29649790
TI  - Evolution of multiple sclerosis prevalence and phenotype in Latin America.
AB  - BACKGROUND: Literature regarding MS epidemiology and phenotype is scarce but has
      increased markedly over the past years. The objective of the present work is to
      assess the evolution of the prevalence and phenotype of MS in Latin America
      during recent years. METHODS: Review of literature. RESULTS: MS prevalence levels
      are low to medium in Latin America, although these have increased in recent
      years. A small latitudinal gradient has also been observed, but exceptions to
      this rule exist, suggesting other genetic and environmental factors ultimately
      influence regional prevalence rates. One of the distinctive features of the
      region is the complex genetic admixture arising from multiple divergent
      population ancestries in different countries including: Native Americans,
      Caucasians and Africans. Another variable which would lower MS risk in the region
      could be a protective effect linked to exposure to certain infections, such as
      parasites. Despite differences in MS epidemiology, Latin American patients show
      an MS phenotype very similar to that of Caucasian patients, and a progressively
      increasing female gender ratio as has been described worldwide. CONCLUSION: MS
      epidemiology in Latin American patients has distinctive features. Both,
      prevalence and incidence, are increasing.

PMID- 29649789
TI  - Improving fatigue in multiple sclerosis by smartphone-supported energy
      management: The MS TeleCoach feasibility study.
AB  - BACKGROUND: Fatigue is a frequently occurring, often disabling symptom in MS with
      no single effective treatment. In current fatigue management interventions,
      personalized, real-time follow-up is often lacking. The objective of the study is
      to assess the feasibility of the MS TeleCoach, a novel intervention offering
      telemonitoring of fatigue and telecoaching of physical activity and energy
      management in persons with MS (pwMS) over a 12-week period. The goal of the MS
      TeleCoach, conceived as a combination of monitoring, self-management and
      motivational messages, is to enhance levels of physical activity thereby
      improving fatigue in pwMS in an accessible and interactive way, reinforcing self
      management of patients. METHODS: We conducted a prospective, open-label
      feasibility study of the MS TeleCoach in pwMS with Expanded Disability Status
      Scale <= 4 and moderate to severe fatigue as measured by the Fatigue Scale for
      Motor and Cognitive Functions (FSMC). Following a 2-week run-in period to assess
      the baseline activity level per patient, the target number of activity counts was
      gradually increased over the 12-week period through telecoaching. The primary
      efficacy outcome was change in FSMC total score from baseline to study end. A
      subset of patients was asked to fill in D-QUEST 2.0, a usability questionnaire,
      to evaluate the satisfaction with the MS TeleCoach device and the experienced
      service. RESULTS: Seventy-five patients were recruited from 16 centres in
      Belgium, of which 57 patients (76%) completed the study. FSMC total score (p =
      0.009) and motor and cognitive subscores (p = 0.007 and p = 0.02 respectively)
      decreased from baseline to week 12, indicating an improvement in fatigue. One
      third of participants with severe fatigue changed to a lower FSMC category for
      both FSMC total score and subscores. The post-study evaluation of patient
      satisfaction showed that the intervention was well accepted and that patients
      were very satisfied with the quality of the professional services. CONCLUSION:
      Using MS TeleCoach as a self-management tool in pwMS suffering from mild
      disability and moderate to severe fatigue appeared to be feasible, both
      technically and from a content perspective. Its use was associated with improved
      fatigue levels in the participants who completed the study. The MS Telecoach
      seems to meet the need for a low-cost, accessible and interactive self-management
      tool in MS.

PMID- 29649791
TI  - The Long-Term Impact of High Levels of Alpha-Melanocyte-Stimulating Hormone in
      Energy Balance Among Obese Adolescents.
AB  - BACKGROUND: Deregulation of orexigenic and anorexigenic pathways occurs among
      adolescents with obesity. Alpha-melanocyte-stimulating hormone (alpha-MSH) is a
      key catabolic mediator of energy homeostasis and an important anorexigenic
      neuropeptide in the control of energy balance and thermogenesis. However, it was
      not well explored if alpha-MSH can modulate long-term weight loss therapy
      responses in a dependent manner according to its concentration. Our hypothesis is
      that a high alpha-MSH concentration at baseline promotes better modulation of
      anorexigenic/orexigenic pathways in obese adolescents. METHODS: One hundred ten
      post-pubertal obese adolescents (body mass index >95th percentile) were submitted
      to 1 year of interdisciplinary therapy (clinical, nutritional, psychological,
      physical exercise, and physiotherapy support). Body composition and plasma levels
      of alpha-MSH, neuropeptide Y (NPY), melanin-concentrating hormone, and agouti
      related peptide (AgRP) were measured before and after therapy. The volunteers
      were grouped on the basis of Tertiles of alpha-MSH concentration: Low (<0.75
      ng/mL), Medium (<=0.76 to >=1.57 ng/mL), and High (>1.57 ng/mL). Significance was
      set as p < 0.05. RESULTS: The treatment promoted a significant improvement in
      body adiposity and fat free mass for all groups. It is important to note that
      only in the high alpha-MSH group, a significant increase of the alpha-MSH/NPY
      ratio and decrease NPY/AgRP ratio post treatment were observed. CONCLUSION: The
      high alpha-MSH concentration promotes better modulation of
      anorexigenic/orexigenic pathways in obese adolescents following long-term weight
      loss therapy and this is important in clinical practice.

PMID- 29649792
TI  - Comparison of Different Compression to Ventilation Ratios (2: 1, 3: 1, and 4: 1)
      during Cardiopulmonary Resuscitation in a Porcine Model of Neonatal Asphyxia.
AB  - BACKGROUND: High-quality chest compression is essential during neonatal
      cardiopulmonary resuscitation (CPR). However, the optimal compression to
      ventilation ratio (C:V) that should be used during neonatal CPR to optimize
      coronary and cerebral perfusion while providing adequate ventilation remains
      unknown. OBJECTIVE: We hypothesized that different C:V ratios (e.g., 2: 1 or 4:
      1) will reduce the time to return of spontaneous circulation (ROSC) in severely
      asphyxiated piglets. METHODS: Thirty-one newborn piglets (1-4 days old) were
      anesthetized, intubated, instrumented, and exposed to 50-min normocapnic hypoxia
      followed by asphyxia. Piglets were randomized into 4 groups: 2: 1 (n = 8), 3: 1
      (n = 8), 4: 1 (n = 8) C:V ratio, or a sham group (n = 7). Cardiac function,
      carotid blood flow, cerebral oxygenation, and respiratory parameters were
      continuously recorded throughout the experiment. RESULTS: Thirty-one piglets were
      included in the study, and there was no difference in the duration of asphyxia or
      the degree of asphyxiation (as indicated by pH, PaCO2, and lactate) among the
      different groups. The median (IQR) time to ROSC was similar between the groups
      with 127 (82-210), 96 (88-126), and 119 (83-256) s in the 2: 1, 3: 1, and 4: 1
      C:V ratio groups, respectively (p = 0.67 between groups). Similarly, there was no
      difference in 100% oxygen requirement or epinephrine administration between the
      experimental groups. CONCLUSIONS: Different C:V ratios resulted in similar ROSC,
      mortality, oxygen, and epinephrine administration during resuscitation in a
      porcine model of neonatal asphyxia.

PMID- 29649793
TI  - Long-Term Effects of Middle Ear Tendon Resection on Middle Ear Myoclonic
      Tinnitus, Hearing, and Hyperacusis.
AB  - OBJECTIVE: To evaluate the therapeutic effects of middle ear tendon resection
      (METR) on middle ear myoclonic tinnitus (MEMT) and to investigate its long-term
      effects on hearing and hyperacusis. MATERIALS AND METHODS: Thirty-seven patients
      with MEMT with a mean age of 33.2 +/- 11.8 years were included in this study.
      METR was performed on all 37 MEMT patients (41 ears) between November 2004 and
      August 2016. The mean follow-up period was 16.1 months. We examined changes in
      tinnitus and accompanying stress and depression in patients after surgery, and
      examined the hearing changes and the occurrence of complications including
      hyperacusis. RESULTS: After surgery, 34 (91.9%) patients exhibited complete
      resolution of MEMT during their follow-up period, and 3 patients showed a partial
      response. The mean Visual Analog Scale (VAS) scores for tinnitus severity, the
      Tinnitus Handicap Inventory (THI), and stress index decreased significantly after
      surgery (p < 0.05, paired t test). No patient developed hearing loss or
      hyperacusis following surgery. Preexisting hyperacusis even improved in most of
      the patients with intractable MEMT after surgery. Recurrence of the symptom
      occurred in only 1 patient, who underwent revision surgery with improvement. We
      observed 1 case of postoperative delayed facial palsy with complete recovery in 2
      weeks. CONCLUSIONS: METR seems to be an effective and safe treatment option for
      intractable MEMT, considering its high control rate of tinnitus and no long-term
      harmful effects on hearing and hyperacusis.

PMID- 29649794
TI  - Effects of Volume Overload and Current Techniques for the Assessment of Fluid
      Status in Patients with Renal Disease.
AB  - Volume overload is an important, may be the foremost, independent prognostic
      factor determining the outcome of hemodialysis patients. Therefore, it is crucial
      to measure fluid status of these patients and avoid volume overload. This review
      aims to evaluate volume overload, its effects on patients with renal diseases and
      current methodologies measuring volume status in the body. These techniques will
      be first classified as clinical evaluation and non-clinical and/or instrumental
      techniques, which includes biomarkers, ultrasonography, relative blood volume
      monitoring, bioimpedance, echocardiography, pulmonary artery catheterization,
      esophageal and/or suprasternal Doppler, and blood viscosity. Advantages and
      limitations of these different techniques will be reviewed extensively by
      comparing each other. At last, insights gained from this review can highlight the
      future prospects in this active area of research.

PMID- 29649795
TI  - Effect of Hybrid Blood Purification Treatment on Secondary Hyperparathyroidism
      for Maintenance Hemodialysis Patients.
AB  - OBJECTIVE: This study aims to investigate the effects of hybrid blood
      purification treatment on secondary hyperparathyroidism for maintenance
      hemodialysis (HD) patients. METHODS: A total of 40 patients were randomly divided
      into 2 groups: HD combined with hemoperfusion (HD + HP) group (n = 20) and HD
      group (n = 20). Changes in intact parathyroid hormone (iPTH) in these 2 groups
      were compared before and after treatment, and iPTH levels in the HD + HP group
      were monitored before and after treatment. RESULTS: iPTH, beta2 microglobulin
      (beta2-MG), and cystatin C (CysC) levels were significantly lower in the HD + HP
      group than in the HD group (p < 0.05), iPTH levels were significantly higher than
      at the first day after treatment (p < 0.05), and iPTH level was significantly
      higher (p < 0.05). CONCLUSION: The clearance effects of HD + HP on iPTH, beta2
      MG, and CysC are better than HD alone. Treatment with HD + HP every 2 weeks is
      recommended for maintenance HD patients.

PMID- 29649796
TI  - Visual Field Variability after Gene Therapy for Leber's Hereditary Optic
      Neuropathy.
AB  - PURPOSE: To assess changes in visual field (VF) values after gene therapy for
      Leber's hereditary optic neuropathy (LHON). METHODS: VF recovery, VF indices, and
      mean deviation in injected and uninjected eyes, before and after gene therapy,
      were examined in 2 groups of patients according to disease duration (<=2 years
      and > 2 years). Nine patients with LHON were treated by monocular intravitreal
      injection of AAV2-ND4. Finally, 7 patients were considered for subsequent
      comparisons; the first and second eyes were treated separately. RESULTS: There
      were no significant differences in VF indices and mean deviation between injected
      and uninjected eyes (p = 0.910 and p = 0.929, respectively). However, there was a
      significant difference before and after injection (p = 0.016 and p = 0.015,
      respectively). There was no significant difference in VF improvement between
      patients with <=2 years' disease duration and those with a longer disease
      duration. CONCLUSION: There was a statistically significant VF improvement after
      gene therapy. This suggests that monocular intravitreal injection of AAV2-ND4 can
      improve binocular VF values. This study also suggests that gene therapy can be
      effective in patients with a disease duration of > 2 years.

PMID- 29649797
TI  - A Multimodal Approach to the Treatment of Intraparenchymal Meningioma in a 7-Year
      Old Boy: A Case Report.
AB  - Intraparenchymal meningiomas are very rare: only 26 cases have been diagnosed in
      patients younger than 20 years since 1954. They can lead to preoperative
      differential diagnosis mistakes due to their atypical neuroimaging appearance. A
      multimodal approach is thus necessary to plan a surgical procedure aiming to
      receive the best extent of resection while preserving the patient's functional
      integrity. The authors report the case of a 7-year-old boy with a history of
      blurred vision, left eye deviation, and weakness on the left side of his body.
      Magnetic resonance imaging (MRI) revealed an intra-axial, cortical, right
      parietal lesion without dural attachment. MR spectroscopy and perfusion study
      were obtained. Since the patient was 100% left-handed, functional MRI, diffusion
      tensor imaging, and neuropsychological evaluation were performed before the
      surgical procedure. Histopathological analysis revealed the mass to be an
      atypical meningioma (WHO grade II). Postoperative MRI indicated complete
      macroscopic lesion removal. The postsurgical neuropsychological profile was not
      different from the profile before surgery. The boy was discharged 3 days after
      the surgical operation without any neurological deficits.

PMID- 29649798
TI  - Factors Associated with Functional Performance among Patients on Hemodialysis in
      Taiwan.
AB  - BACKGROUND/AIMS: We investigated factors associated with functional performance
      in hemodialysis (HD) patients as well as their relationships with mortality.
      METHODS: We enrolled 790 HD patients who were followed up from 2009 to 2013.
      Functional performance was evaluated by Karnofsky Performance Status Scale (KPSS)
      scores. We examined the associations of clinical variables and all-cause
      mortality with KPSS scores. RESULTS: Of the participants, 460 had high KPSS
      scores (range 90-100) and 330 had low KPSS scores (below 80). On multivariate
      analysis, age and weekly HD sessions were associated with significantly increased
      odds of a lower KPSS score (age: OR 1.05, 95% CI 1.04-1.07, p < 0.001; weekly HD:
      OR 2.10, 95% CI 1.37-3.21, p = 0.001). A low KPSS score was a significant
      predictor of increased all-cause mortality (hazard ratio 1.49; 95% CI 1.02-2.16,
      p = 0.037), as determined using Cox regression analysis. CONCLUSION: Functional
      performance was associated with clinical variables and all-cause mortality in HD
      patients.

PMID- 29649800
TI  - Is There Enough Evidence to Prove That Hemodiafiltration Is Superior?
AB  - The evidence concerning online hemodiafiltration (HDF) includes the following:
      (1) the increase of removal of uremic toxin, (2) the prevention of dialysis
      rerated hypotension, (3) the recovery of survival, and (4) the recovery of
      dialysis related uncertain symptoms. Although clinical evidence has been noted,
      the hypothesis of the efficacy of HDF are still indefinite and require further
      precise research.

PMID- 29649799
TI  - Fallacies and Pitfalls of Dialysis Sodium Prescription and Control.
AB  - Dialysate conductivity is routinely used as a surrogate for dialysate sodium
      concentration. However, dialysis machine manufacturers apply different
      conductivity temperature correction coefficients. With the same conductivity in
      dialysis machines manufactured by different manufacturers, dialysate sodium may
      significantly differ. Also, electrolyte prescriptions are individualized (K, Ca,
      HCO3) and this is associated with another variation in dialysate sodium in the
      order of 1-5 mmol/L and both deviations are cumulative and chronic for each
      patient. Equivalence of the prescribed dialysate sodium and the concentration
      measured in it is not granted. Both variables differ and it is machine dependent!
      This paper analyses those variations from a technical point of view and suggests
      how to detect them and how to deal with or avoid them in clinical practice.

PMID- 29649801
TI  - An Ultrasound Study of the Development of Lingual Coarticulation during
      Childhood.
AB  - BACKGROUND/AIMS: There is growing evidence that coarticulation development is
      protracted and segment-specific, and yet very little information is available on
      the changes in the extent of coarticulation across different phonemes throughout
      childhood. This study describes lingual coarticulatory patterns in 6 age groups
      of Scottish English-speaking children between 3 and 13 years old. METHODS:
      Vowelon-consonant anticipatory coarticulation was analysed using ultrasound
      imaging data on tongue shape from 4 consonants that differ in the degree of
      constraint, i.e., the extent of articulatory demand, on the tongue. RESULTS:
      Consonant-specific age-related patterns are reported, with consonants that have
      more demands on the tongue reaching adolescent-like levels of coarticulation in
      older age groups. Within-speaker variability in tongue shape decreases with
      increasing age. CONCLUSION: Reduced coarticulation in the youngest age group may
      be due to insufficient tongue differentiation. Immature patterns for lingual
      consonants in 5- to 11-year-olds are explained by the goal of producing the
      consonant target overriding the goal of coarticulating the consonant with the
      following vowel.

PMID- 29649802
TI  - Is There Not Sufficient Evidence to Show That Haemodiafiltration Is Superior to
      Conventional Haemodialysis in Treating End-Stage Kidney Disease Patients?

PMID- 29649803
TI  - Sound Symbolic Patterns in Pokemon Names.
AB  - This paper presents a case study of sound symbolism, cases in which certain
      sounds tend to be associated with particular meanings. We used the corpus of all
      Japanese Pokemon names available as of October 2016. We tested the effects of
      voiced obstruents, mora counts, and vowel quality on Pokemon characters' size,
      weight, strength parameters, and evolution levels. We found that the number of
      voiced obstruents in Pokemon names correlates positively with size, weight,
      evolution levels, and general strength parameters, except for speed. We argue
      that this result is compatible with the frequency code hypothesis of Ohala. The
      number of moras in Pokemon names correlates positively with size, weight,
      evolution levels, and all strength parameters. Vowel height is also shown to have
      an influence on size and weight - Pokemon characters with initial high vowels
      tend to be smaller and lighter, although the effect size is not very large. Not
      only does this paper offer a new case study of sound symbolism, it provides
      evidence that sound symbolism is at work when naming proper nouns.

PMID- 29649804
TI  - Regional Variation in Fundamental Frequency of American English Vowels.
AB  - We examined whether the fundamental frequency (f0) of vowels is influenced by
      regional variation, aiming to (1) establish how the relationship between vowel
      height and f0 ("intrinsic f0") is utilized in regional vowel systems and (2)
      determine whether regional varieties differ in their implementation of the
      effects of phonetic context on f0 variations. An extended set of acoustic
      measures explored f0 in vowels in isolated tokens (experiment 1) and in connected
      speech (experiment 2) from 36 women representing 3 different varieties of
      American English. Regional differences were found in f0 shape in isolated tokens,
      in the magnitude of intrinsic f0 difference between high and low vowels, in the
      nature of f0 contours in stressed vowels, and in the completion of f0 contours in
      the context of coda voicing. Regional varieties utilize f0 control in vowels in
      different ways, including regional f0 ranges and variation in f0 shape.

PMID- 29649805
TI  - Comparing the Efficacy of CBASP with Two Versions of CBT for Depression in a
      Routine Care Center: A Randomized Clinical Trial.
AB  - BACKGROUND: The cognitive-behavioral analysis system of psychotherapy (CBASP) was
      developed for the treatment of chronic, early-onset depression. However, it is
      unclear whether this approach can be recommended for depression in general
      (episodic and chronic), and no direct comparisons between CBASP with different
      versions of cognitive-behavioral therapy (CBT) exist. METHODS: A randomized
      controlled trial compared 3 treatment conditions (all lasting 16 sessions) with a
      waiting list group (WL): CBASP, CBT with a focus on physical exercise (CBT-E),
      and CBT with a focus on pleasurable, low-energy and mindful activities (CBT-M).
      We included 173 patients and involved 41 therapists. Assessments were at
      baseline, after session 8, and at the end of treatment. RESULTS: Our primary
      outcome Beck Depression Inventory-II indicated a general advantage of the CBT
      arms compared to CBASP [F(6, 154.5) = 4.2, p = 0.001], with significant contrasts
      in particular in favor of CBT-E. Effect sizes against WL were d = 0.91 (CBT-E),
      0.87 (CBT-M), and 0.47 (CBASP). A triple interaction with an additional factor
      "chronic versus episodic depression" [F(6, 142.7) = 2.2, p = 0.048] indicated
      that the treatments resulted in different outcomes, with best results again for
      CBT-E in particular in episodic depression. Responder rates indicated significant
      improvements (56% in both CBT arms, 34% in the CBASP arm, 3.4% in WL; intention
      to-treat samples). As compared to CBASP, response rates were significantly higher
      for CBT-E (OR = 2.48; 95% CI = 1.02-6.00) and CBT-M (OR = 2.46; 95% CI = 1.01
      6.01). CONCLUSIONS: CBASP was more effective than WL, but less effective than the
      2 CBT arms. This was mainly caused by an advantage of CBT interventions in
      episodic depression.

PMID- 29649806
TI  - Rituximab in Refractory Chronic Spontaneous Urticaria: An Encouraging Therapeutic
      Approach.
AB  - BACKGROUND: Chronic spontaneous urticaria (CSU) is a frequent mast cell-driven
      disease that affects approximately 0.5-1% of the population. Antihistamines are
      currently the drugs of choice in patients with CSU. Omalizumab has been shown to
      be very effective in CSU and has been recently approved as second-line therapy.
      However, although its introduction has markedly improved the therapeutic
      possibilities for CSU, there is still a hard core of patients who do not respond
      and require effective treatment. METHODS: We report the case of a patient who
      achieved an 8-month remission of refractory CSU following the use of rituximab,
      and perform a review of the literature regarding the use of rituximab in CSU.
      RESULTS: There was a remarkable improvement in her CSU after the administration
      of rituximab maintained over time. CONCLUSION: Rituximab is a chimeric
      murine/human monoclonal antibody directed against CD20, which depletes memory B
      lymphocytes that are necessary for autoantibody production. The abrogation of the
      autoantibody production is the proposed mechanism by which it may alleviate the
      symptoms of CSU.

PMID- 29649807
TI  - The Ho Chi Minh City Society of Dialysis Therapies.

PMID- 29649808
TI  - Treatment of Complicated Urinary Tract Infections in Individuals with Chronic
      Neurogenic Lower Urinary Tract Dysfunction: Are Antibiotics Mandatory?
AB  - INTRODUCTION: Urinary tract infections (UTI) in patients with neurogenic lower
      urinary tract dysfunction (NLUTD) are defined as complicated UTI requiring
      antibiotic treatment. As the emergence of multiresistant strains is a serious
      problem, we assessed the feasibility of nonantibiotic treatment of UTI in
      patients with NLUTD. MATERIALS AND METHODS: In a prospective study evaluating the
      usefulness of UTI prophylaxis, participants could opt for either antibiotic or
      nonantibiotic treatment of breakthrough UTI. If either symptoms persisted for 48
      h or a febrile UTI occurred, antibiotic treatment based on microbiological
      testing was mandatory. Treatment efficacy, complications, and emergency hospital
      visits were assessed. RESULTS: Within the observation period (1 year), the 25
      participants developed 206 UTI. Seven febrile UTI required immediate antibiotic
      treatment. Of the remaining 199 UTI, patients chose antibiotic treatment in 104
      events, whereas in 95 events, patients chose either nonantibiotic interventions
      (n = 80) or no treatment at all (n = 15). Success rates were 78.8% for antibiotic
      treatment, 67.5% with nonantibiotic treatments, and 26% without therapy. Of the 7
      patients with initially febrile UTI, 2 required hospitalization due to
      septicemia. CONCLUSIONS: Nonantibiotic treatment seems to be a feasible
      alternative to antibiotic therapy in patients with complicated UTI as well,
      provided there is no fever.

PMID- 29649809
TI  - Body Mass Index and Cardiovascular Risk Factors in Children and Adolescents with
      High Birth Weight.
AB  - BACKGROUND/AIMS: This study aimed to identify a possible association among high
      birth weight with overweight/obesity, high arterial blood pressure, dyslipidemia,
      and insulin resistance in children and adolescents. METHODS: This is a cross
      sectional study with 719 children and adolescents (6-12 years) stratified
      according to birth weight (low birth weight [LBW] <2,500 g, adequate birth weight
      [ABW] 2,500-3,999 g, and high birth weight [HBW] >=4,000 g). Data collected were
      anthropometric data, arterial blood pressure levels, lipid profile, and insulin
      resistance (fasting glucose and insulin, used to calculate homeostatic model
      assessment-IR). RESULTS: The mean age of schoolchildren was 9.5 +/- 2.0 years and
      371 (51.6%) were male. LBW and HBW were observed in 79 of 719 (10.9%) and 40 of
      719 (55.6%) children/adolescents, respectively. There was no increased risk of
      overweight (OR 0.9; 95% CI 0.4-2.1; p = 0.964) and obesity (OR 1.4; 95% CI 0.6
      3.5; p = 0.588) in HBW group compared to LBW and ABW groups. HBW was not
      associated with high blood pressure, dyslipidemia, and insulin resistance. The
      LBW group was independently associated with higher values of systolic (OR 1.07;
      95% CI 1.05-1.10; p < 0.01) and diastolic blood pressure (OR 1.04; 95% CI 1.00
      1.07; p = 0.044). CONCLUSION: There was no association between HBW with
      overweight/obesity and classic cardiovascular risk factors in this group of
      children/adolescents. Only LBW was related to higher blood pressure levels.

PMID- 29649810
TI  - Female Gender, Marital and Family Problems, and Feelings of Guilt Are Related to
      Self-Immolation Suicide Attempts.
AB  - BACKGROUND: Self-immolation (SI) is considered one of the most painful, dramatic,
      and at the same time most inexplicable methods of suicide, with a high social
      impact. Prevalence rates are particularly high in Iran, and in north-western Iran
      specifically. Here, we report sociodemographic, psychological, and psychiatric
      characteristics of patients attempting self-immolation (PSIs), compared to
      patients with accident burns (PABs). METHOD: Patients referred to the Burns
      Emergency Unit of the Besat Hospital (Hamadan, Iran) were enrolled in the present
      study between winter 2015 and summer 2016. After burn-related treatments and
      surgery, a thorough interview was undertaken covering sociodemographic
      characteristics, burn-related information, and psychiatric background. RESULTS: A
      total of 79 patients were enrolled. Among these, 19 (31.7%) had attempted suicide
      via SI. Compared to the PABs, the PSIs were predominantly females; they reported
      family and marital problems as the main triggers for SI. The psychiatric
      interviews indicated that PSIs often suffered from major depressive disorders,
      adjustment disorders, and bipolar disorders. The prevailing feelings reported
      were guilt and shame. A binary logistic regression showed that feelings of guilt
      and marital and family problems predicted SI. CONCLUSIONS: The prevalence of SI
      was surprisingly high. Marital and family conflicts as a proxy for highly
      distressing social interactions, along with female gender and feelings of guilt
      and shame were strongly associated with SI. Family and couple counseling
      specifically tailored to difficulties experienced by women might reduce the risk
      of SI.

PMID- 29649811
TI  - Transcription Elongation Factor P-TEFb Is Involved in IL-17F Signaling in Airway
      Smooth Muscle Cells.
AB  - BACKGROUND: IL-17F is involved in the pathogenesis of several inflammatory
      diseases, including asthma and COPD. However, the effects of steroids on the
      function of IL-17F signaling mechanisms are largely unknown. One of the
      transcription elongation factors, positive transcription elongation factor b (P
      TEFb) composed of cyclin T1 and cyclin-dependent kinase 9 (CDK9), is known as a
      novel checkpoint regulator of gene expression via bromodomain-containing protein
      4 (Brd4). METHODS: Human airway smooth muscle cells were stimulated with IL-17F
      and the expression of IL-8 was evaluated by real-time PCR and ELISA. Next, the
      phosphorylation of CDK9 was determined by Western blotting. The CDK9 inhibitor
      and short interfering RNAs (siRNAs) targeting Brd4, cyclin T1, and CDK9 were used
      to identify the effect on IL-17F-induced IL-8 expression. Finally, the effect of
      steroids and its signaling were evaluated. RESULTS: IL-17F markedly induced the
      transcription of the IL-8 gene and the expression of the protein. Pretreatment of
      CDK9 inhibitor and transfection of siRNAs targeting CDK9 markedly abrogated IL
      17F-induced IL-8 production. Transfection of siRNAs targeting Brd4 and cyclin T1
      diminished IL-17F-induced phosphorylation of CDK9 and IL-8 production. Moreover,
      budesonide decreased CDK9 phosphorylation and markedly inhibited IL-17F-induced
      IL-8 production. CONCLUSIONS: This is the first report that P-TEFb is involved in
      IL-17F-induced IL-8 expression and that steroids diminish it via the inhibition
      of CDK9 phosphorylation. IL-17F and P-TEFb might be novel therapeutic targets for
      airway inflammatory diseases.

PMID- 29649812
TI  - Safety and Efficacy of a Progressively Prolonged Maintenance Interval of Venom
      Immunotherapy.
AB  - BACKGROUND: The long-term protection provided by venom immunotherapy (VIT) is
      related to the dose administered and to its long duration; the latter, however,
      becomes inconvenient for patients in countries like Greece, with many islanders
      or inhabitants of distant mountainous areas. Maintenance interval prolongation
      reduces the number of office visits - saving time and money - and as a
      consequence contributes to the patients' compliance. The aim of this prospective
      study was to evaluate the safety and efficacy of VIT on a progressively prolonged
      maintenance interval (PPMI). METHOD: 450 venom-allergic patients were reviewed
      for participation in our study; all of them were initially treated with a
      modified rush or an ultrarush protocol using freshly reconstituted, pure venoms.
      Upon reaching the maintenance dose, the VIT interval was scheduled to be
      gradually prolonged - by 1 week each time - aiming at a maximal interval of 26
      weeks. RESULTS: 267/450 patients consented to participate in our VIT PPMI
      protocol: 98 were treated with vespid(s) venom, 142 with honeybee venom, and 27
      with both. The mean duration of patient follow-up was 9.1 +/- 4.2 years. The
      majority of systemic reactions due to VIT injections occurred up to the 8-weeks
      PPMI; few additional reactions were documented in a small fraction (2.9%) of our
      patient population beyond 9 weeks and up to 16 weeks; all were caused by honeybee
      VIT. No reactions were observed during VIT administration at the 26-week
      interval. Ninety-six patients reported 204 field sting occurrences by the culprit
      insect. Ten systemic reactions (8 mild and 2 moderate in severity) were
      registered between the 9- and 18-week PPMI; the honeybee was the culprit insect
      in all cases. 108 field stings by the offending insect were sustained beyond the
      20- and up to the 26-week PPMI; there were no reactions at all. CONCLUSIONS:
      Progressively prolonging the VIT maintenance interval up to 26 weeks appears to
      be safe and efficacious.

PMID- 29649813
TI  - Different Characteristics, Clinical Outcomes, and Left Atrial Reverse Remodeling
      in Patients with Mitral Stenosis Maintaining Sinus Rhythm for at Least 10 Years
      after Successful Percutaneous Mitral Valvuloplasty.
AB  - BACKGROUND: We aimed to investigate the characteristics and echocardiographic
      changes in patients with severe mitral stenosis (MS) who maintained sinus rhythm
      (SR) for at least 10 years after successful percutaneous mitral balloon
      valvuloplasty (PMV). METHODS: We retrospectively reviewed 107 patients who had
      successful PMV and follow-up echocardiography for at least 10 years without
      mitral valve surgery. Preprocedural, immediate postprocedural (PMV), and long
      term follow-up echocardiography (at least 10 years after PMV) data were reviewed.
      RESULTS: The mean follow-up time after PMV was 15 +/- 4 years for SR patients (n
      = 50) and 16 +/- 4 years (p = 0.172) for atrial fibrillation (AF) patients (n =
      57). The left atrial diameter was significantly decreased in SR patients in the
      follow-up echocardiography images compared to its pre-PMV value (46.7 +/- 6.3 vs.
      43.3 +/- 6.2 mm, respectively), whereas it was significantly increased in
      patients with AF (53.9 +/- 7.1 vs. 58.1 +/- 8.7 mm). In multivariate analysis,
      preprocedural AF (odds ratio [OR] 14.50, p = 0.001) and LA diameter >=50 mm (OR
      8.81, p < 0.001) were independently associated with increased risk for the
      presence of AF after successful PMV. CONCLUSION: Very long-term maintenance of SR
      after successful PMV was associated with preprocedural SR and LA diameter < 50
      mm.

PMID- 29649814
TI  - What Is the Role of Barbed Suture in Laparoscopic Myomectomy? A Meta-Analysis and
      Pregnancy Outcome Evaluation.
AB  - BACKGROUND: This work analyzes the feasibility and effectiveness of barbed suture
      during laparoscopic myomectomy. METHODS: Eight works have been carefully examined
      for the meta-analysis from all papers published online until November 2017.
      RESULTS: Barbed suture proved to be superior to traditional suture technique in
      blood loss in laparoscopic myomectomy (Standardized Mean Difference [SMD] -0.650,
      95% CI -1.420 to -0.119, p = 0.098, test for heterogenity p < 0.0001, I2 =
      95.54%), Hb drop (SMD -1.452, 95% CI -3.590 to 0.687, p = 0.183, test for
      heterogenity p < 0.0001, I2 = 99.08%), suturing difficulty (SMD -0.638, 95% CI 
      0.935 to -0.342, p <= 0.001, test for heterogenity p = 0.25, I2 = 27.84%),
      suturing time (SMD -1.197, 95% CI -1.848 to -0.549, p <=0.001, test for
      heterogenity p = 0.0001, I2 = 83.30%) and total operative time (SMD -0.687, 95%
      CI -0.804 to -0.569, p <= 0.001, test for heterogenity p = 0.292, I2 = 17.44%).
      Barbed suture demonstrated to be better in comparison with the control group even
      with regard to the length of hospitalization (SMD -0.278, 95% CI -0.543 to 0.012,
      p = 0.040, test for heterogenity p = 0.025, I2 = 61.85%), and to perioperative
      complications (SMD 0.708, 95% CI 0.503-0.996, p = 0.048, test for heterogenity p
      = 0.79, I2 = 0%). CONCLUSION: Barbed suture significantly facilitates
      laparoscopic myomectomy by reducing the total operative/suturing time, estimated
      blood loss/Hb drop, and reduction of perioperative complications.

PMID- 29649815
TI  - Testicular Germ-Cell Tumours: A Descriptive Analysis of Clinical Characteristics
      at First Presentation.
AB  - INTRODUCTION: Clinical characteristics of testicular germ cell tumours (GCTs)
      apparently change over time, and some vary geographically. The aim of this study
      is to document the clinical profile of contemporary GCT patients. PATIENTS AND
      METHODS: Four hundred twenty-two Caucasian GCT-patients treated in one German
      centre during 2000-2017, were analysed in terms of patient-age, laterality,
      histology, tumour-size, clinical stages (CS), pathological (pT)-stages and serum
      biomarker expression. The results were analysed descriptively and compared with
      the literature. RESULTS: Median age was 36 years and 60.2% had seminoma. Betaeta
      human chorionic gonadotropin was expressed in 37.9% and alpha Fetoprotein in
      25.6%. CS1 presenting stage was 66.6% of all GCT patients, 79.1% in seminoma, and
      47.6% in nonseminoma. Tumour size was significantly associated with pT-stages and
      CS. Patients >50 years had significantly more seminoma (77.6%) than younger ones
      (57.9%). Comparison with literature data revealed a shifting towards higher age,
      lower CS, higher proportion of seminoma and striking differences of
      characteristics among geographic regions. CONCLUSIONS: A typical contemporary
      clinical profile of testicular GCTs is presented in this study. Median age,
      relative incidence of seminoma and proportion of CS1 appear to be increasing over
      time. Striking differences among ethnic groups regarding the characteristics of
      GCT require further investigation.

PMID- 29649816
TI  - In vitro Antichlamydial Activity of 1,2,3,5-Tetrasubstituted Pyrrole Derivatives.
AB  - BACKGROUND: Chlamydia is a group of bacterial pathogens distributed worldwide
      that can lead to serious reproductive and other health problems. The rise of
      antibiotic-resistant pathogens promotes the development of novel antichlamydial
      agents. The aim of this study is to assess in vitro antichlamydial activity of
      our previously synthesized 1,2,3,5- tetrasubstituted pyrroles. METHODS: The
      derivatives were screened for their antichlamydial activity against three
      Chlamydia strains by calculating IC50 values using concentration-response
      inhibition data between 1 and 32 MUM. The action of the compounds on Chlamydia
      elementary body (EB) infectivity and the impact of the chemicals' administration
      time on their antichlamydial effect were evaluated to reveal the inhibitory
      mechanism. RESULTS: Some of the compounds moderately inhibited the Chlamydia
      strains. Compound 10 exhibited the strongest inhibitory activity, with IC50
      values from 4.34 to 5.83 MUM. These pyrrole derivatives inhibited Chlamydia
      infection by reducing EB infectivity during the early stage and disturbing
      Chlamydia growth by targeting the early-to-middle stage prior to 12 h of the
      chlamydial life cycle. CONCLUSION: Our findings highlight the potential of
      1,2,3,5-tetrasubstituted pyrrole derivatives as promising lead molecules for the
      development of antichlamydial agents.

PMID- 29649817
TI  - Overactive Bladder Symptoms after Transobturator Sling Surgery for Pure Stress
      Urinary Incontinence: A Cross-Sectional Comparative Study.
AB  - INTRODUCTION: Transobturator tape (TOT) surgery has been associated with
      increased overactive bladder (OAB) although much controversy exists. METHODS: In
      a cross-sectional study, women who underwent TOT surgery for pure stress
      incontinence (MonarcTM) answered the 6 questions of the symptom bother (SB)
      subscale of the OAB questionnaire - short form (OABq-SF) and an additional
      question regarding whether symptoms began after surgery. Women with SB score over
      the 4th quartile (>=30/100) were reassessed after a longer follow-up. Patients
      from primary care were recruited as controls. RESULTS: We recruited 213 patients
      (135 in the TOT group and 78 age-adjusted controls). The mean age of operated
      patients was 58.7 +/- 10.1 years with a mean follow-up of 25.9 +/- 13.2 months.
      OABq-SF SB scores did not differ between the TOT group and controls
      (respectively, 18.5 +/- 30 and 15.5 +/- 6.7, p = 0.202). A total of 48% patients
      reported no relationship between symptoms and surgery. Highly symptomatic
      operated patients were reassessed after a longer follow-up (46.3 +/- 10.6
      months). The mean score in the second follow-up (n = 25) was not statistically
      different from the first assessment (46.4 +/- 22.7 and 58.1 +/- 19.8, p = 0.059).
      CONCLUSIONS: Women who underwent TOT surgery did not show increased OAB SB scores
      when compared to controls. Our study suggests that OAB symptoms may thus be
      present but overlooked during initial clinical assessment.

PMID- 29649818
TI  - The Risk of Human Papillomavirus Infection for Spontaneous Abortion, Spontaneous
      Preterm Birth, and Pregnancy Rate of Assisted Reproductive Technologies: A
      Systematic Review and Meta-Analysis.
AB  - AIMS: To estimate the impact of human papillomavirus (HPV) infection on
      spontaneous abortion, spontaneous preterm birth (sPTB), pregnancy rate of females
      undergoing assisted reproductive technologies (ART), and spontaneous abortion of
      ART pregnancy. METHODS: PubMed, Medline, Embase, and the Cochrane Library were
      searched until December 16, 2016. The OR or relative risk (RR) with its
      corresponding 95% CI were selected as effect size. Subgroup analysis of HPV
      genotype infection (high-risk HPV [HR-HPV] or indiscriminate genotype) was
      performed. Statistical analysis was conducted using STATA 12.0. RESULTS: Eighteen
      studies were included. Eight studies revealed no significant association between
      HPV infection and spontaneous abortion (OR 1.40, 95% CI 0.56-3.50). However,
      subgroup analysis showed indiscriminate genotype HPV infection increased the
      ratio of spontaneous abortion with OR of 2.24 (95% CI 1.37-3.65), while HR-HPV
      infection had no significant effect (OR 0.65, 95% CI 0.21-1.98). The results
      indicated that HR-HPV infection was a risk for sPTB with a pooled OR of 2.84 (95%
      CI 1.95-4.14). HPV infection was found to be independent of the ART-based
      clinical pregnancy rate (RR 1.04, 95% CI 0.64-1.70) and spontaneous abortion of
      ART pregnancy (RR 1.47, 95% CI 0.86-2.50). CONCLUSIONS: Indiscriminate HPV
      genotype infection can increase the risk of spontaneous abortion and HR-HPV
      infection was a risk factor for sPTB. However, there was not enough evidence to
      indicate the association between HPV infection and pregnancy rate of ART, and
      spontaneous abortion of ART pregnancy. Different genotypes of HPV infection may
      play a discrepant role in adverse pregnancy outcomes.

PMID- 29649819
TI  - Patent Foramen Ovale and Cryptogenic Stroke or Transient Ischemic Attack: To
      Close or Not to Close? A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: The optimal strategy of secondary stroke prevention in patients with
      patent foramen ovale (PFO) is controversial. This study was performed to evaluate
      the efficacy and safety of the device closure (DC) versus the medical therapy
      (MT) in patients with cryptogenic stroke or transient ischemic attack (TIA) and
      PFO. SUMMARY: Randomized controlled trials with active and control groups
      receiving the DC plus MT and MT alone in patients with history of cryptogenic
      stroke/TIA and diagnosis of PFO were systematically searched. The main efficacy
      outcome was stroke recurrence. Subgroup-analyses were performed according to age,
      shunt size, and presence of atrial septal aneurysm (ASA). Safety endpoints
      included any serious adverse event (SAE), atrial fibrillation (AF), and major
      bleeding complications. Risk ratios (RRs) and hazard ratios (HRs) with 95% CIs
      were estimated. Five trials were included, involving 3,440 participants (DC =
      1,829, MT = 1,611). There was a protective effect of closure in the risk of
      recurrent stroke (RR 0.43 [0.21-0.90]; p = 0.024; HR = 0.39 [0.19-0.83]; p =
      0.014). The benefit of PFO closure was significant in patients with PFO
      associated with substantial right-to-left shunt or ASA. There were no differences
      in the risks of SAEs and major bleedings between the groups. The rate of new
      onset AF was higher in the DC than in the MT arm (RR 4.46 [2.35-8.41]; p <
      0.001). Successful device implantation and effective PFO closure were achieved in
      96 and 91% of the patients respectively. Key Messages: In selected adult patients
      with PFO and history of cryptogenic stroke, the DC plus MT is more effective to
      prevent stroke recurrence and is associated with an increased risk of new-onset
      AF compared to the MT alone.

PMID- 29649820
TI  - Accuracy of Acid-Base Diagnoses Using the Central Venous Blood Gas in the Medical
      Intensive Care Unit.
AB  - BACKGROUND: Acid-base disturbances are frequent in critically ill patients.
      Arterial blood gas (ABG) is the gold standard in the diagnosis of these
      disturbances, but it is invasive with potential hazards. For patients with a
      central venous catheter, venous blood gas (VBG) sampling may be an alternative,
      less-invasive diagnostic tool. However, the accuracy of a central VBG-based acid
      base disorder diagnosis compared to an ABG is unknown. The primary objective of
      this study was to assess the accuracy of a central VBG-based acid-base disorder
      diagnosis compared to the "gold standard" ABG in critically ill patients.
      METHODS: This was a study of adult patients in a medical intensive care unit that
      had simultaneously drawn ABG and central VBG samples. Expert acid-base
      diagnosticians, all nephrologists, diagnosed the acid-base disorder(s) in each
      blood gas sample. The central VBG diagnostic accuracy was assessed with percent
      agreement, sensitivity, and specificity compared to the ABG-based diagnosis.
      RESULTS: The study involved 23 participants. Overall, the central VBG had 100%
      sensitivity for metabolic acidosis, metabolic alkalosis, and respiratory
      acidosis, and lower sensitivity (71%) for respiratory alkalosis, and high percent
      agreement, ranging from 75 to 94%. VBG-based diagnoses in vasopressor-dependent
      patients (n = 13, 56.5%) performed similarly to the entire sample. CONCLUSIONS:
      In critically ill adult patients, central VBG may be used to detect and diagnose
      acid-base disturbances with reasonable diagnostic accuracy, even in shock states,
      compared to the ABG. This study supports the use of central VBG for diagnosis of
      acid-base disturbances in critically ill patients.

PMID- 29649821
TI  - 135th Congress of the German Society of Surgery (DGCH).

PMID- 29649822
TI  - Abstracts of the 30th Meeting of the European Renal Cell Study Group (ERCSG).

PMID- 29649823
TI  - Diagnostic Accuracy of Low and Ultra-Low Dose CT for Identification of Urinary
      Tract Stones: A Systematic Review.
AB  - BACKGROUND: Non-contrast computed tomography of the kidneys, ureters, and bladder
      (CT KUB) is the investigation of choice for renal colic; however, radiation
      exposure can be a concern. AIMS: The study aimed to investigate the diagnostic
      accuracy of low dose (LD) and ultra-low dose (ULD) CT of the urinary tract for
      detection of urinary tract stones in patients with renal colic. METHODS: A
      Cochrane style systematic review of the literature from 1995 to 2017 was carried
      out. Literature search and data extraction were conducted by 2 reviewers.
      Specificity and sensitivity values were calculated for LD (<3.5 mean radiation
      dose [mSv]) and ULD (<1.9 mSv) CT separately. RESULTS: A total of 12 studies were
      included following screening. A total of 1,529 patients were included in the
      review (475 in the LD group and 1,054 in the ULD group). Using standard dose CT
      KUB as the reference standard, the sensitivity of LD CT KUB ranged from 90 to 98%
      and specificity from 88 to 100%. The sensitivity of ULD CT KUB ranged from 72 to
      99% and the specificity ranged from 86 to 100%. The diagnostic accuracy for LD CT
      was 94.3% and for ULD CT was 95.5%. CONCLUSIONS: LD and ULD CT KUB provide
      effective methods of identifying urinary tract stones. High diagnostic accuracy,
      sensitivity, and specificity are maintained despite significant radiation dose
      reduction in comparison to standard dose CT.

PMID- 29649824
TI  - End-Organ Saturation Differences in Early Neonatal Transition for Left- versus
      Right-Sided Congenital Heart Disease.
AB  - BACKGROUND: For neonates with congenital heart disease (CHD), left-sided (LL) and
      right-sided (RL) single ventricular physiologies (LL, hypoplastic left heart
      syndrome; RL, tricuspid atresia or pulmonary atresia with intact ventricular
      septum) may demonstrate distinct changes in tissue saturation in the first 72 h
      of life. Near-infrared spectroscopy (NIRS) can measure regional cerebral
      saturation (Csat) and renal saturation (Rsat) to clarify differences between LL
      and RL over time. OBJECTIVES: Our primary objective was to measure changes in
      Csat and Rsat in the first 72 h of life using NIRS between CHD infants with LL
      compared to RL. The secondary objective was to correlate NIRS values to an
      echocardiographic marker of perfusion. METHOD: Newborns with hypoplastic left
      heart syndrome, tricuspid atresia, and pulmonary atresia with intact ventricular
      septum from 2013 to 2016 underwent routine NIRS monitoring. Csat, Rsat, and
      systemic saturations (SpO2) in the first 72 h of life were retrospectively
      analyzed and the echocardiographic descending aorta velocity time integral (VTI)
      was measured. Mixed effects models compared differences over time between LL and
      RL. RESULTS: The final cohort included 13 LL, 12 RL, and 4 controls. Csat
      decreased for RL compared to LL (p = 0.005), while Rsat decreased for both (p =
      0.008). Over time, SpO2 increased for LL but decreased for RL (p = 0.046).
      Compared to the controls, infants with CHD had lower Csat, lower Rsat, and lower
      SpO2. The descending aorta VTI was correlated with Rsat (R2 = 0.24, p = 0.02).
      CONCLUSION: NIRS Csat measures were better preserved in LL compared to RL. Rsat
      decreased in both groups through time. The correlation between the descending
      aorta VTI and Rsat suggests an association between NIRS measures of renal
      saturation and renal perfusion.

PMID- 29649825
TI  - The Role of Staging Laparoscopy in Resectable and Borderline Resectable
      Pancreatic Cancer: A Systematic Review and Meta-Analysis.
AB  - AIM: The study aimed to determine the additional value of staging laparoscopy in
      patients with pancreatic cancer deemed potentially resectable based on computed
      tomography imaging. METHODS: A systematic literature search was performed using
      MEDLINE and the Cochrane Register of Controlled Trials (January 1995 to June
      2017). Primary outcome measures were the overall yield and sensitivity to detect
      non-resectable disease. Quality of studies was assessed with the Newcastle-Ottawa
      Scale. RESULTS: From 156 records, 15 studies including 2,776 patients met the
      inclusion criteria. In 12 studies, reporting outcomes on 1,756 patients with
      resectable disease after standard imaging, 350 (20%, range 14-38%) cases of non
      resectable cancer were detected with staging laparoscopy. In 3 studies on 242
      patients with locally advanced disease after standard imaging, staging
      laparoscopy detected metastases in 86 patients (36%). The failure rate of staging
      laparoscopy to detect non-resectable disease was 5% (64 of 1,406). CONCLUSION:
      Staging laparoscopy reduces the non-therapeutic laparotomy rate, and in locally
      advanced or borderline resectable disease, staging laparoscopy could more
      accurately select patients for neoadjuvant protocols.

PMID- 29649826
TI  - Erratum.
AB  - In the abstract of the article by V. Calabrese et al. entitled "Early Diastolic
      Dysfunction after Cancer Chemotherapy: Primary Endpoint Results of a Multicenter
      Cardio-Oncology Study" [Chemotherapy 2018; 63: 55-63, DOI: 10.1159/000486761],
      the sixth sentence should read:"Eighty patients (68 females, 12 males, median age
      49 years) were evaluated at 1 week after chemotherapy (T1)."

PMID- 29649827
TI  - Effects of Driving Skill Training on Safe Driving in Older Adults with Mild
      Cognitive Impairment.
AB  - BACKGROUND: Driving cessation is strongly associated with adverse health outcomes
      in the older adults. Although there were numerous documentations of driving
      rehabilitation in disabled adults, the effects of interventions on safe driving
      were not clear in older adults with cognitive impairment who had low driving
      skills. OBJECTIVE: This randomized controlled trial was designed to determine
      whether a safe driving skill program consisting of classroom and on-road training
      could enhance driving performance of older drivers with cognitive impairment in
      Japan. METHODS: A total of 160 community-living older drivers participated in the
      randomized controlled trial with blinded endpoint assessment. Participants
      randomized to intervention underwent 10 1-h classroom sessions and 10 1-h on-road
      sessions focused on common problem areas of older drivers. Controls received 1
      classroom education. On-road driving performance was assessed by certified
      driving school instructors in a driving school. The participants carried out
      dynamic vision and cognitive performance tests. RESULTS: One hundred and forty
      six (intervention group, n = 71) subjects completed the 3-month follow-up. Mean
      adherence to classroom-based vision training and driving simulator training and
      on-road training programs, including the 71 participants, was 99.0 +/- 6.4 and
      99.0 +/- 7.2%, respectively. Regarding the safe driving skill score, there were
      group * time interactions (p < 0.01) indicating benefits of the intervention over
      time. Although there were no significant group * time interactions in cognitive
      tests, dynamic vision showed group * time interactions (p < 0.01). CONCLUSION:
      The driving skill program significantly improved safe driving performance in
      older adults with cognitive impairment who were at a potentially high risk of a
      car accident.

PMID- 29649828
TI  - Risk Analysis for Invasive Fungal Infection after Living Donor Liver
      Transplantation: Which Patient Needs Potent Prophylaxis?
AB  - BACKGROUND: Invasive fungal infection (IFI) is associated with high mortality
      after living donor liver transplant (LDLT). The aim of this study was to identify
      the risk factors for post-LDLT IFI for early diagnosis and improvement of
      antifungal treatment outcome. METHODS: Risk analysis data were available for all
      153 patients who underwent LDLT between January 2005 and April 2012. RESULTS:
      During the follow-up period (1,553 +/- 73 days, range 20-2,946 days), 15 patients
      (9.8%) developed IFI classified as "proven" (n = 8) and "probable" (n = 7) with
      fungal pathogens including Candida spp. (n = 10), Aspergillus spp. (n = 4), and
      Trichosporon (n = 2). Of these patients, 7 patients with IFI died despite
      treatment. The 1-, 3-, and 5-year survival rates were lower in patients with IFI
      than those without IFI (66.7/59.3/44.4 vs. 90.4/85.7/81.8%, respectively; p =
      0.0026). Multivariate analysis identified model for end-stage liver disease score
      of >=26 (OR 16.0, p = 0.0012) and post-transplant acute kidney injury (RIFLE
      criteria I- or F-class; OR 4.87, p = 0.047) as independent risk factors for IFI.
      CONCLUSION: Preoperative recipients' status and postoperative kidney dysfunction
      can affect an occurrence of post-transplant IFI. These risk factors would be
      taken into consideration for designation of proper antifungal therapy.

PMID- 29649829
TI  - Relation of Retinopathy of Prematurity to Brain Volumes at Term Equivalent Age
      and Developmental Outcome at 2 Years of Corrected Age in Very Preterm Infants.
AB  - BACKGROUND: Retinopathy of prematurity (ROP) is a major complication of preterm
      birth and has been associated with later visual and nonvisual impairments.
      OBJECTIVES: To evaluate relationships between any stage of ROP, brain volumes,
      and developmental outcomes. METHODS: This study included 52 very preterm infants
      (gestational age [mean +/- SD]: 26.4 +/- 1.9 weeks). Total brain, gray matter,
      unmyelinated white matter (UWMV), and cerebellar volumes were estimated in 51 out
      of 52 infants by magnetic resonance imaging at term-equivalent age. Bayley Scales
      of Infant Development were used to assess developmental outcomes in 49 out of 52
      infants at a mean corrected age of 24.6 months. RESULTS: Nineteen out of 52
      infants developed any stage of ROP. Infants with ROP had a lower median (IQR)
      UWMV (173 [156-181] vs. 204 [186-216] mL, p < 0.001) and cerebellar volume (18.3
      [16.5-20] vs. 22.3 [20.3-24.7] mL, p < 0.001) than infants without ROP. They also
      had a lower median (IQR) mental developmental index (72 [56-83] vs. 100 [88-104],
      p < 0.001) and a lower psychomotor developmental index (80 [60-85] vs. 92 [81
      103], p = 0.002). Brain volumes and developmental outcomes did not differ among
      infants with different stages of ROP. CONCLUSION: Any stage of ROP in preterm
      infants was associated with a reduced brain volume and an impaired developmental
      outcome. These results suggest that common pathways may lead to impaired neural
      and neurovascular development in the brain and retina and that all stages of ROP
      may be considered in future studies on ROP and development.

PMID- 29649830
TI  - Healthcare-Associated Infections after Lower Urinary Tract Endoscopic Surgery:
      Analysis of Risk Factors, Associated Microorganisms and Patterns of Antibiotic
      Resistance.
AB  - OBJECTIVES: To review the incidence of healthcare-associated infections/urinary
      tract infection (UTI), risk factors, microorganisms isolated and antibiotic
      resistances in patients who underwent lower urinary tract endoscopic surgery
      (LUTES) in a tertiary care hospital. METHODS: A prospective observational study
      was carried out including 1,498 patients who undergo LUTES. Patients with and
      without UTI after surgery were compared. We analysed infection incidence, risk
      factors, microorganisms isolated and antibiotic resistances. RESULTS:
      Postoperative UTI incidence was 4.7%. Risk factors found: higher American Society
      of Anesthesiologists classification (OR 2.82; 95% CI 1.8-4.5; p < 0.00),
      immunosuppression (OR 2.89; 95% CI 1.2-7.2; p = 0.01), indwelling urinary
      catheter prior admission (OR 2.6; 95% CI 1.6-4.2; p < 0.00) and postoperative
      catheterization longer than 2 days (OR 1.74; 95% CI 1.7-4.3; p < 0.00).
      Transurethral resection of the bladder (TURB) had the highest infection rates
      (5.5%). Microorganisms isolated were Pseudomonas aeruginosa (23.5%), Escherichia
      coli (17.6%), Klebsiella pneumoniae and Enterococcus spp (11.8%). Resistance
      rates for flourquinolones varied between 28 and 80%, and Carbapenem-resistant
      Enterobacteriaceae rose up 20%. CONCLUSIONS: Low percentage of UTI after
      endoscopic surgery was registered. TURB was the procedure with highest infection
      rate. Pseudomonas aeruginosa stands out as the most frequently isolated
      microorganism. Patient comorbidities, previous urinary catheter and postoperative
      catheter were identified as risk factors.

PMID- 29649831
TI  - What Is the Best Way to Prepare A Buccal Mucosa Graft for Urethroplasty? A
      Histology-Based Preliminary Report.
AB  - PURPOSE: To evaluate the histological characteristics of buccal mucosa samples
      prepared using different dissection techniques. METHODS: The buccal mucosae
      harvested from 9 men submitted to a substitution urethroplasty were used in this
      study. Biopsy specimens of buccal mucosae were grouped according to the
      macroscopic appearance after dissection: Group 1 - yellowish appearance (minimal
      dissection), Group 2 - whitish appearance (more aggressive dissection), and Group
      3 - translucent appearance (ultra-aggressive dissection). The biopsy specimens
      were evaluated using histomorphometric techniques. The thicknesses of the graft,
      epithelium, and sub-epithelial connective tissue were compared. RESULTS: The
      samples from Group 3 and Groups 2 and 3 presented lower total and lower sub
      epithelial connective tissue thickness, respectively, when compared with Group 1.
      The epithelial thickness was not affected by the dissection method. Muscular and
      adipose tissues were present in 77 and 55% of samples from Group 1, respectively,
      whereas these were observed in 44 and 22% of samples from Group 2 respectively.
      The muscular tissue was observed in 11% of the cases, and the adipose tissue was
      not observed in samples prepared with ultra-aggressive dissection. CONCLUSION: We
      conclude that an intermediate graft dissection (whitish appearance, as performed
      in Group 2) presents the best balance between subepithelial connective tissue
      preservation and adipose and muscle tissue removal.

PMID- 29649832
TI  - The Impact of Preexisting Chronic Kidney Disease on the Severity and Recovery of
      Acute Kidney Injury.
AB  - BACKGROUND: Recent observational studies have shown that in chronic kidney
      disease (CKD) patients, a significantly smaller percentage of patients with an
      episode of acute kidney injury (AKI) have full recovery of renal function
      compared to those without CKD. However, precise mechanisms involved in the
      incomplete repair after AKI with preexisting CKD have not been completely
      ascertained. Here, we assessed the impact of preexisting CKD on the severity and
      recovery of AKI in a mouse model of 5/6 nephrectomy. METHODS: Male CD-1 mice
      underwent 5/6 nephrectomy (Nx). Six weeks post surgery, ischemia reperfusion
      injury (IRI) or a sham operation was performed and functional, histological, and
      various molecular parameters were compared between them. RESULTS: Serum
      creatinine level on day 1 after IRI was comparable between control and Nx mice.
      However, serum creatinine remained significantly higher throughout the recovery
      phase in Nx mice compared to control mice. mRNA and protein expression of the
      cell cycle regulatory proteins were persistently elevated in Nx mice and this was
      associated with significantly increased levels of the G1 cell cycle arrest
      markers. Treatment with a p53 inhibitor following IRI resulted in not only
      decreased expression of G1 arrest markers but also decreased fibrosis, suggesting
      that prolonged epithelial G1 cell cycle arrest might be partially responsible for
      impaired recovery from superimposed AKI on CKD. CONCLUSION: Taken together,
      reduced nephron mass have a negative effect on the repair process that is
      partially mediated by the disruption of the cell cycle regulation.

PMID- 29649834
TI  - Aktualisierte Empfehlungen zur Behandlung der Immunthrombozytopenie.

PMID- 29649833
TI  - Suctioning Minimally Invasive Percutaneous Nephrolithotomy with a Patented System
      Is Effective to Treat Renal Staghorn Calculi: A Prospective Multicenter Study.
AB  - OBJECTIVES: To investigate the safety, efficacy, and practicability of minimally
      invasive percutaneous nephrolithotomy (MPCNL) with the aid of a patented
      irrigation clearance system in treating renal staghorn calculi. METHODS: From
      August 2009 to July 2014, 4 hospitals had executed a prospective multicenter
      study with a total of 912 cases. The patients were randomly divided into 3
      groups: suctioning MPCNL, standard percutaneous nephrolithotomy (PCNL), and
      traditional MPCNL groups. Multiple operative and perioperative parameters were
      compared. RESULTS: Blood loss and intrapelvic pressure in the suctioning MPCNL
      group were significantly less than those in the standard PCNL group. The average
      operation time, intrapelvic pressure, and amount of bleeding in the suctioning
      MPCNL group were better than those in the traditional MPCNL group. The suctioning
      MPCNL used one tract more frequently and 2 or 3 tracts less frequently than the
      standard MPCNL and traditional MPCNL groups. The stone-free rate by one surgery
      in the suctioning MPCNL group was significantly higher than that in standard PCNL
      and traditional MPNCL groups. CONCLUSIONS: Suctioning MPCNL using our patented
      system shows several advantages in treating renal staghorn calculi, including
      minimal invasion, shorter operation time, lower intrapelvic pressure, less
      bleeding and the need for a smaller number of -percutaneous tracts, and higher
      stone clearance rate by one -surgery.

PMID- 29649835
TI  - Immunthrombozytopenie - aktuelle Diagnostik und Therapie: Empfehlungen einer
      gemeinsamen Arbeitsgruppe der DGHO, OGHO, SGH, GPOH und DGTI.

PMID- 29649836
TI  - [Flight Routes to Germany of Seriously Ill Children and Adolescents From Former
      Eastern Bloc Countries for Treatment of Renal Failure].
AB  - BACKGROUND: Increased patient mobility and restricted treatment of children with
      end-stage renal disease forced families from the former Eastern Bloc countries to
      flee with their children to Germany for adequate medical treatment. METHODS: In a
      case study, the patients' charts were analysed retrospectively. In structured
      interviews, parents and patients were asked about their flight routes to Germany,
      their medical treatment and their integration. RESULTS: From 2003 to 2013, eight
      children and adolescents with renal failure were treated with dialysis or renal
      transplantation in Erlangen. Most patients came with the help of human
      traffickers and a tourist visa. They often told that they had lost their papers
      in the excitement. One family received new passports from the trafficker with
      fake names and birth dates. The families had to pay high amounts of money in
      order to save their child's life. Although dialysis therapy was often difficult
      because of lower adherence, the overall course was satisfactory. Four patients
      have been transplanted successfully so far. CONCLUSION: This case study reveals
      new facets of patient mobility, since leaving home was the only way for the
      family to ensure their child's survival. An ethical problems arose, as a chronic
      dialysis treatment in children seems ethically only justifiable if a kidney
      transplant is the therapeutic goal. .

PMID- 29649837
TI  - [Cost-Effectiveness and Cost-Utility Analyses of Antireflux Medicine].
AB  - INTRODUCTION: Laparoscopic antireflux surgery and medical therapy with proton
      pump inhibitors are gold standards of gastroesophageal reflux treatment. On
      account of limited resources and increasing healthcare needs and costs, in this
      analysis, not only optimal medical results, but also superiority in health
      economics of these 2 methods are evaluated. METHODS: We performed an electronic
      literature survey in MEDLINE, PubMed, Cochrane Library, ISRCTN (International
      Standard Randomization Controlled Trial Number) as well as in the NHS Economic
      Evaluation Database, including studies published until 1/2017. Only studies
      considering the effect size of QALY (Quality-Adjusted Life Years) (with respect
      to different quality of life-scores) as primary outcome comparing laparoscopic
      fundoplication and medical therapy were included. Criteria of comparison were
      ICER (Incremental Cost-Effectiveness Ratio) and ICUR (Incremental Cost-Utility
      Ratio). Superiority of the respective treatment option for each publication was
      worked out. RESULTS: In total, 18 comparative studies were identified in the
      current literature with respect to above-mentioned search terms, qualifying for
      the defined inclusion criteria. Six studies were finally selected for analyses.
      Out of 6 publications, 3 showed superiority of laparoscopic fundoplication over
      long-term medical management based on current cost-effectiveness data.
      Limitations were related to different time intervals, levels of evidence of
      studies and underlying resources/costs of analyses, healthcare systems and
      applied quality of life instruments. CONCLUSION: Future prospective, randomized
      trials should examine this comparison in greater detail. Additionally, there is a
      large potential for further research in the health economics assessment of early
      diagnosis and prevention measures of reflux disease and Barrett's
      esophagus/carcinoma.

PMID- 29649838
TI  - [Limbokeratoplasty to Treat Lattice and Granular Corneal Dystrophies].
AB  - The surgical technique of limbokeratoplasty (limbo-KP) was initially established
      for the treatment of severe limbal deficiencies. Besides improving visual acuity,
      surgery is aimed at ensuring complete, long-lasting epithelialization of the
      ocular surface. Due to the extension of the indication spectrum, limbo-KPs are
      also used in various forms of epithelial/stromal corneal dystrophies such as
      lattice and granular (transforming growth factor beta-induced [TGFBI] gene
      mutation associated) dystrophies. The objective of limbo-KP is to ensure
      prolonged clear graft survival without a recurrence of the dystrophy as otherwise
      observed after conventional keratoplasty.

PMID- 29649839
TI  - [The 2016 Activity Report of the Tissue Transplantation and Biotechnology Section
      of the German Ophthalmological Society].

PMID- 29649840
TI  - [Therapeutic Concepts for Treatment of Patients with Non-infectious Uveitis
      Biologic Disease Modifying Antirheumatic Drugs].
AB  - Biologic disease modifying antirheumatic drugs (bDMARDs) can be highly efficient
      in the treatment of various non-infectious uveitis entities. Currently, the TNF
      alpha-inhibitor Adalimumab is the only in-label therapeutic option, whereas, all
      other bDMARDs need to be given as an off-label therapy. bDMARDs are indicated in
      diseases refractory to conventional synthetic DMARD therapy and/or systemic
      steroids, or in patients in whom treatment with those is not possible due to side
      effects. Therapeutic mechanisms currently employed are cytokine-specific
      (interferons, inhibition of TNF-alpha or of interleukin [IL]-1-, IL-6- or IL-17
      signalling), inhibit T cell costimulation (CTLA-4 fusion protein), or act via
      depletion of B cells (anti-CD20). All bDMARDs need to be administered
      parenterally, and therapy is initiated by the treating internal specialist only
      after interdisciplinary coordination of all treating subspecialties and after
      exclusion of contraindications. Regular clinical and laboratory monitoring is
      mandatory for all patients while under bDMARD therapy.

PMID- 29649841
TI  - Gastric peroral endoscopic myotomy for the treatment of refractory gastroparesis:
      a multicenter international experience.
AB  - BACKGROUND:  Gastroparesis is a difficult-to-treat motility disorder with a poor
      response to medical therapy. Gastric peroral endoscopic pyloromyotomy (G-POEM)
      has been offered as a novel therapy in the treatment of refractory gastroparesis.
      We present a multicenter case series of our experience with G-POEM. METHODS: 
      This is an international multicenter case series of patients who underwent G-POEM
      for the treatment of gastroparesis. The severity of gastroparesis was assessed by
      delayed gastric emptying scintigraphy (GES) and an elevated gastroparesis
      cardinal symptoms index (GCSI). Patients then underwent G-POEM using the
      submucosal tunneling technique. The primary endpoint was improvement in the GCSI
      score and improvement in gastric emptying on repeat scintigraphy. Secondary
      endpoints were technical success, complication rate, procedure duration, and
      length of hospital stay post-procedure. RESULTS:  G-POEM was technically
      successful in all 33 patients. Symptomatic improvement was seen in 28/33 patients
      (85 %), with a decrease in symptom score by GCSI from 3.3 to 0.8 at follow-up (P
      < 0.001). The mean procedure duration was 77.6 minutes (37 - 255 minutes). Mean
      GES improved significantly from 222.4 minutes to 143.16 minutes (P < 0.001).
      Complications were minimal and included bleeding (n = 1) and an ulcer (n = 1)
      treated conservatively. The mean length of hospital stay post-procedure was 5.4
      days (1 - 14 days). The mean follow-up duration was 11.5 months (2 - 31 months).
      CONCLUSION:  G-POEM is a technically feasible, safe, and successful procedure for
      the treatment of refractory gastroparesis. A further multicenter comparative
      study should be performed to compare this technique to laparoscopic
      pyloromyotomy.

PMID- 29649842
TI  - Anabolic Activity of a Soy Extract and Three Major Isoflavones in C2C12 Myotubes.
AB  - Isoflavones have been reported to stimulate muscle growth. The aim of this in
      vitro study was to examine anabolic activity and associated molecular mechanisms
      of a soy extract (SoyEx), isoflavone aglycones, and a mixture simulating the
      composition of SoyEx in C2C12 myotubes. C2C12 cells were differentiated into
      myotubes. The effects of SoyEx, genistein, daidzein, glycitein, and the mixture
      of genistein-daidzein-glycitein (Mix) on myotube diameter and number were
      determined. In addition, the expression of genes and proteins associated with
      anabolic activity was analyzed. Treatment with SoyEx, genistein, and Mix led to a
      significant increase of myotube diameter and an increase of the number of
      myotubes per area compared to the control cell. The increase of diameter by SoyEx
      was antagonized by an antiestrogen, not by an antiandrogen. Furthermore, gene
      expressions of insulin growth factor (IGF)-1 and its receptor (IGF-1R), as well
      as protein expression of myosin heavy chain (MHC), were significantly increased
      by SoyEx, genistein, and Mix. The effects induced by genistein and Mix were
      comparable to SoyEx. In conclusion, SoyEx displays an anabolic activity in C2C12
      myotubes by binding to ER and modulating IGF-1 and MHC expression. Our studies
      with isoflavone aglycones and Mix indicate that the isoflavone aglycone with the
      highest anabolic bioactivity in SoyEx is genistein.

PMID- 29649843
TI  - [Aspects of Palliative Care: Finding the Right Balance].

PMID- 29649844
TI  - [A 10-Year-Old Boy with a Skin Rash on the Face and on Both Forearms].

PMID- 29649845
TI  - [(Early) Palliative Care in Emergency Medicine].
AB  - At the end of life patients with a life-limiting disease are often admitted to
      emergency departments (ED). Mostly, in the setting of an ED there may not be
      enough time to meet the needs for palliative care (PC) of these patients.
      Therefore, integration of PC into the ED offers a solution to improve their
      treatment. In the outpatient setting a cooperation between prehospital emergency
      services, the patient's general practitioner and specialized outpatient PC teams
      may allow the patient to die at home - this is what most patients prefer at the
      end of life. Furthermore, due to the earlier integration of PC after admission
      the hospital stay is shortened. Also the number of PC consultations may increase.
      Additionally, a screening of PC hneeds among all patients visiting the ED may be
      beneficial: to avoid not meeting existing PC needs and to standardize the need of
      PC consultation. An example for such a screening tool is the "Palliative Care and
      Rapid Emergency Screening" (P-CaRES).

PMID- 29649846
TI  - [Palliative Home Care Teams in Germany].
AB  - Since 2007, patients with severe advanced life-limiting illnesses and high,
      complex symptom burdens have a right to receive specialized outpatient palliative
      care (SAPV). Multi-professional teams with heterogeneous organizational
      structures provide care in cooperation with primary care givers, not limited to
      cancer patients. The aim of SAPV is to foster patient's autonomy and quality of
      life. SAPV can be provided as counseling of patient and care givers, coordination
      of care, additional supportive and full care provision. While the basis of SAPV
      provision is regulated by a SAPV directive, different contracts between care
      providers and health care insurances regulate organization, cooperation,
      definition of care levels, service provision and compensation. Some regions have
      model contracts that are binding for all SAPV teams in the area; in other regions
      teams negotiate e. g. compensation, individually with insurances. The article
      gives an overview of the regulations regarding SAPV.

PMID- 29649847
TI  - [Special Palliative Care in Patients With Non-oncological Diseases].
AB  - Palliative medicine has become an integral part of the German healthcare system
      in recent years. However, patients with non-malignant diseases have less access
      to palliative care than patients with oncological diseases. These patients
      comprise a heterogeneous group of chronic lung and heart diseases, neurological
      and geriatric diseases. Their symptom burden and their palliative care needs are
      similar to those of oncological patients, but earlier in the disease process.
      Physical aspects of the disease process are different from psychological, social
      and spiritual aspects. General medical and specialized palliative care should be
      offered depending on the complexity of patient's needs. Screening tools are
      helpful in identifying patients who need palliative care early in the course of
      the disease. Advance planning should be an integral part of caring for these
      patients.

PMID- 29649848
TI  - [Palliative Sedation - Despite Guidelines a Difficult Process of Decisions].
AB  - A distinction needs to be made between intermediate and continuous sedation as
      well as between minimal, moderate and deep sedation. To gain ethical acceptance
      it is crucial that for palliative sedation (PS) minimally required doses are
      administered to decrease suffering. Intermittent PS is used for decreasing
      physical symptoms, whereas deep continuous PS is used to minimize intolerable
      suffering or psychological symptoms. Precise medical indication and education of
      patient and relatives are pre-requirements to any PS. Midazolam is often applied
      for PS. Each PS requires frequent monitoring and personal assistance.

PMID- 29649849
TI  - [COPD - Importance of Lung Function Testing for Diagnosis and Treatment].
AB  - Pulmonary function testing is essential for diagnosis and treatment-guidance of
      chronic obstructive pulmonary disease (COPD). Airway obstruction as assessed by
      spirometry should follow the reference-values provided by the Global Lung
      Initiative (GLI) of the European Respiratory Society (ERS). In addition, lung
      function testing should also include the assessment of lung hyperinflation and
      pulmonary emphysema by full-body plethysmography and determination of diffusion
      capacity. This is important since both, lung hyperinflation and pulmonary
      emphysema, can present without existing airway obstruction. Even though this
      formally excludes the diagnosis of COPD, these entities still belong to this
      disease complex. However, strictly speaking, pharmaceutical treatment is valid
      only for those patients with co-existing airway obstruction according to Global
      Lung Initiative for Chronic Obstructive Lung Disease (GOLD) criteria - since the
      absence of airway obstruction serves as exclusion criterion in nearly all
      randomized controlled trials. Nevertheless, progressive symptoms still require
      detailed pulmonary function testing for the guidance of non-pharmaceutical
      treatment - such as endoscopic or surgical lung volume reduction, long-term
      oxygen therapy, long-term non-invasive ventilation, and lung transplantation.

PMID- 29649850
TI  - [Diagnostic and Treatment Strategies in Morel-Lavallee Lesions in the Spinal
      Column and Pelvis].
AB  - BACKGROUND: The Morel-Lavallee lesion is one of the concomitant soft tissue
      lesions of pelvic fractures. Its role in spine fractures and its treatment in
      combination with osteosynthesis of pelvic or spine fractures have not yet been
      determined. The aim of this study was to analyse the best diagnostic and
      treatment options of both spine and pelvic fractures combined with Morel-Lavallee
      lesions (MLL). METHODS: An analysis of the literature was performed via PubMed
      and Medline. This revealed a total of 197 studies and case reports. After
      analysing the literature, 19 studies/case reports met our inclusion criteria.
      RESULTS: There are several diagnostic options for MLL, including ultrasound,
      computed tomography or MRI. In spinal and pelvic lesions, ultrasound is capable
      of detecting MLL. Some authors tend to perform open debridement of the MLL,
      whereas others recommend percutanous treatment. Open debridement and vacuum
      assisted closure are recommended in late diagnosed MLL, where primary suture of
      the soft tissue is impossible. Fracture fixation should be performed
      simultaneously to treatment of the MLL. Broad-spectrum cephalosporins combined
      with an aminoglycoside or piperacilline/tazobactam should be initiated.
      CONCLUSION: Radical debridement and drainage are recommended, especially when MLL
      is diagnosed late. Repeated ultrasound examinations should be performed of the
      surrounding soft tissue of the fracture. When MLL is diagnosed within 2 days,
      percutanous fracture and MLL treatment should be performed. After more than 2
      days, both fracture and MLL should be treated with open debridement, open
      fracture fixation and primary suture if possible.

PMID- 29649851
TI  - Primary Malignant Melanoma in the Pineal Region: Case Report and Literature
      Review.
AB  - BACKGROUND:  Primary pineal malignant melanoma is a rare type of primary central
      nervous system melanoma with only 19 cases reported in the literature. CASE
      REPORT:  We present a case of a 53-year-old man with primary melanoma of the
      pineal region. He presented to the emergency department with gait unsteadiness
      and ataxia. Magnetic resonance imaging (MRI) revealed a 22 * 17 * 22-mm mass in
      the pineal region. On MRI the tumor was hyperintense in T1, isointense in T2, and
      on T1-weighted images with gadolinium enhancement it appeared homogeneously
      hyperintense with hypointense spots. Our patient underwent subtotal tumor
      resection as well as radiotherapy. The 52-week MRI control showed no recurrence
      of the lesion.After 62 weeks he developed gait ataxia and headaches and was
      admitted to the emergency department. Computed tomography revealed tumor bleeding
      and obstructive hydrocephalus.An external ventricular drain was placed, but the
      bleeding progressed, and 7 days after admission, MRI showed bleeding in the
      thalamus and mesencephalon. With a dismal prognosis, therapy was discontinued. He
      died 65 weeks after diagnosis. METHODS:  We reviewed the available literature
      (PubMed) with 19 published cases of primary pineal malignant melanoma and
      evaluated the common symptoms at presentation, histopathologic features,
      radiologic findings, therapeutic regimens, and time of survival to provide the
      most up-to-date treatment. RESULTS:  The median age of patients with primary
      pineal malignant melanoma is 52 years (female-to-male ratio: 10:10 years); a
      common first sign is chronic hydrocephalus. On MRI the lesion presents
      hyperintense in T1 and hypo- to isointense in T2. Biopsy or resection and
      histopathologic analysis are the key to diagnosis. Common histopathologic
      features are melanic pigment (n = 19/20), positive Human Melanoma Black (HMB-45)
      marker (n = 13/20), positive S100 protein reactivity (n = 11/20), as well as
      positive Melan-A (n = 9/20). The median survival was > 56.5 weeks in patients
      treated with resection and radiation. CONCLUSION:  Reconsidering the reported
      cases surgical treatment followed by radiation increases the length of survival.

PMID- 29649852
TI  - Outcome Predictors of the Transforaminal Endoscopic Spine System Technique for
      Single-level Lumbar Disk Herniation.
AB  - BACKGROUND:  Endoscopic spine surgery has become increasingly popular. However,
      no study has researched the predictive factors for different outcomes. This study
      is the first to evaluate the outcome predictors of the transforaminal endoscopic
      spine system (TESSYS) technique for lumbar disk herniation (LDH). METHODS:  We
      performed a prospective study of 80 patients meeting the inclusion criteria who
      underwent TESSYS for LDH. Clinical outcomes were assessed by the visual analog
      scale (VAS), the Oswestry Disability Index (ODI), and the modified MacNab
      criteria. Univariate and multivariate analyses were performed to evaluate the
      outcome predictors. RESULTS:  There were 36 men and 44 women with a mean age of
      48.76 +/- 15.60 years (range: 24-78 years). The mean follow-up time was 25.15 +/-
      9.76 months (range: 12-48 months). The VAS and ODI scores at the last follow-up
      were significantly improved (p < 0.001). Based on the modified MacNab criteria,
      the global outcomes were excellent in 34 patients (42.5%), good in 26 patients
      (32.5%), fair in 11 patients (13.75%), and poor in 9 patients (11.25%). The
      percentage of symptomatic improvement was 88.75%, and the success rate (excellent
      or good) was 75%. In the univariate and multivariate analyses, LDH with older age
      (odds ratio [OR]: 6.621; 95% confidence interval [CI], 0.632-20.846; p = 0.019),
      high-intensity zone (HIZ) (OR: 8.152; 95% CI, 0.827-4.380; p = 0.003), and larger
      disk herniation (OR: 6.819; 95% CI, 0.113-4.825; p = 0.017) were the most
      significant negative outcome predictors. CONCLUSIONS:  TESSYS is an effective
      method to treat LDH. Older age, the existence of an HIZ, and a large disk
      herniation were the most important predictors for a worse outcome.

PMID- 29649853
TI  - Phenotypic characteristics of the p.Asn215Ser (p.N215S) GLA mutation in male and
      female patients with Fabry disease: A multicenter Fabry Registry study.
AB  - BACKGROUND: The p.Asn215Ser or p.N215S GLA variant has been associated with late
      onset cardiac variant of Fabry disease. METHODS: To expand on the scarce
      phenotype data, we analyzed natural history data from 125 p.N215S patients (66
      females, 59 males) enrolled in the Fabry Registry (NCT00196742) and compared it
      with data from 401 patients (237 females, 164 males) harboring mutations
      associated with classic Fabry disease. We evaluated interventricular septum
      thickness (IVST), left ventricular posterior wall thickness (LVPWT), estimated
      glomerular filtration rate and severe clinical events. RESULTS: In p.N215S males,
      mildly abnormal mean IVST and LVPWT values were observed in patients aged 25-34
      years, and values gradually increased with advancing age. Mean values were
      similar to those of classic males. In p.N215S females, these abnormalities
      occurred primarily in patients aged 55-64 years. Severe clinical events in
      p.N215S patients were mainly cardiac (males 31%, females 8%) while renal and
      cerebrovascular events were rare. Renal impairment occurred in 17% of p.N215S
      males (mostly in patients aged 65-74 years), and rarely in females (3%).
      CONCLUSION: p.N215S is a disease-causing mutation with severe clinical
      manifestations found primarily in the heart. Cardiac involvement may become as
      severe as in classic Fabry patients, especially in males.

PMID- 29649855
TI  - A Salmonella Typhi ghost induced by the E gene of phage phiX174 stimulates
      dendritic cells and efficiently activates the adaptive immune response.
AB  - Previously, we genetically engineered a Salmonella Typhi bacterial ghost (STG) as
      a novel inactivated vaccine candidate against typhoid fever. The underlying
      mechanism employed by the ghost in stimulating the adaptive immune response
      remains to be investigated. In this study, we aimed to evaluate the
      immunostimulatory effect of STG on mouse bone marrow-derived dendritic cells
      (BMDCs) and its activation of the adaptive immune response in vitro. Immature
      BMDCs were stimulated with STG, which efficiently stimulated maturation events in
      BMDCs, as indicated by upregulated expressions of CD40, CD80, and major
      histocompatibility complex class II molecules on CD11+ BMDCs. Immature BMDCs
      responded to STG stimulation by significantly increasing the expression of
      interleukin (IL)-6, which might indicate the induction of dendritic cell
      maturation in vivo (p < 0.05). In addition, ghost-stimulated murine BMDCs showed
      significant expressions of interferon gamma and IL-4, which can drive the
      development of Th1 and Th2 cells, respectively, in co-cultured CD4+ T cells in
      vitro. These results suggest that STG can effectively stimulate maturation of
      BMDCs and facilitate subsequent immune responses via potent immunomodulatory
      cytokine responses.

PMID- 29649854
TI  - Effect of superoxide dismutase, catalase, and glutathione peroxidase
      supplementation in the extender on chilled semen of fertile and hypofertile dogs.
AB  - This study investigated the correlation between oxidative stress status and key
      canine sperm parameters and the effect of addition of a superoxide dismutase
      (SOD), catalase (CAT), and glutathione peroxidase (GPx) combination in egg yolk
      tris-citrate glucose (EYT-G) extender on semen during 10 days of storage at 4C.
      Ten Boxer dogs were divided into two groups, fertile (F) and hypofertile (H),
      depending on pregnancy and live birth rate status in the previous year. Semen
      evaluation was performed on the day of collection (D0) and after 5 (D5) and 10
      (D10) days of cooled storage. Sperm motility, kinetic parameters, and DNA
      integrity were assessed. A correlation between oxidative status and key semen
      parameters in both F and H groups was observed. Total and progressive motilities
      were significantly higher in the treated (SOD, CAT, and GPx addition) versus
      control groups at D10 in both F and H groups, and at D5 in the H group. DNA
      integrity was significantly higher in both treated groups (H and F) at D5 and
      D10. In conclusion, the addition of SOD, CAT, and GPx in the extender allows
      preservation of semen quality for up to 10 days of storage at 4C in both fertile
      and hypofertile dogs.

PMID- 29649856
TI  - Kilovoltage radiotherapy for companion animals: dosimetric comparison of 300 kV,
      450 kV, and 6 MV X-ray beams.
AB  - Radiotherapy for the treatment of cancer in companion animals is currently
      administered by using megavoltage X-ray machines. Because these machines are
      expensive, most animal hospitals do not perform radiotherapy. This study
      evaluated the ability of relatively inexpensive kilovoltage X-ray machines to
      treat companion animals. A simulation study based on a commercial treatment
      planning system was performed for tumors of the brain (non-infectious
      meningoencephalitis), nasal cavity (malignant nasal tumors), forefoot (malignant
      muscular tumors), and abdomen (malignant intestinal tumors). The results of
      kilovoltage (300 kV and 450 kV) and megavoltage (6 MV) X-ray beams were compared.
      Whereas the 300 kV and 6 MV X-ray beams provided optimal radiation dose
      homogeneity and conformity, respectively, for brain tumors, the 6 MV X-rays
      provided optimal homogeneity and radiation conformity for nasal cavity, forefoot,
      and abdominal tumors. Although megavoltage X-ray beams provided better radiation
      dose distribution in most treated animals, the differences between megavoltage
      and kilovoltage X-ray beams were relatively small. The similar therapeutic
      effects of the kilovoltage and 6 MV X-ray beams suggest that kilovoltage X-ray
      beams may be effective alternatives to megavoltage X-ray beams in treating
      cancers in companion animals.

PMID- 29649857
TI  - Oxidative stress and hepatic injury induced in mice fed a Sarcocystis hirsuta
      cyst extract.
AB  - We studied the toxic effects of a Sarcocystis hirsuta cyst extract fed to mice.
      Degenerative changes were found in mice gavage-fed fresh, frozen, and heat
      treated S. hirsuta cyst extract. There were increases in the levels of serum
      aspartate aminotransferase and alanine aminotransferase as well as hepatic and
      brain malondialdehyde (MDA) levels along with concomitant decreases in catalase
      (CAT) and superoxide dismutase (SOD) activities of mice receiving fresh and
      frozen S. hirsuta extracts. Gavage feeding of heat-treated S. hirsuta cyst
      extract had no effects on liver enzymes or brain MDA content, but the liver MDA
      level did increase. Mice in the heat-treated cyst group showed reduced CAT and
      SOD activities as well as increased hepatic MDA levels compared to those in the
      control group. These results indicate that an extract of S. hirsuta cyst can
      induce oxidative stress and hepatic injury, even after heat treatment.

PMID- 29649858
TI  - Pharmacokinetics of enrofloxacin HCl-2H2O (Enro-C) in dogs and
      pharmacokinetic/pharmacodynamic Monte Carlo simulations against Leptospira spp.
AB  - Pharmacokinetic/pharmacodynamic (PK/PD) ratios of reference enrofloxacin (Enro-R)
      and enrofloxacin as HCl-2H2O (Enro-C), as well as Monte Carlo simulations based
      on composite MIC50 and MIC90 (MIC, minimum inhibitory concentration) vs.
      Leptospira spp., were carried out in dogs after their intramuscular (IM) or oral
      administration (10 mg/kg). Plasma determination of enrofloxacin was achieved by
      means of high-performance liquid chromatography. Maximum plasma concentration
      values after oral administration were 1.47 +/- 0.19 MUg/mL and 5.3 +/- 0.84
      MUg/mL for Enro-R and Enro-C, respectively, and 1.6 +/- 0.12 MUg/mL and 7.6 +/-
      0.93 MUg/mL, respectively, after IM administration. Areas under the plasma vs.
      time concentration curve in 24 h (AUC0-24) were 8.02 MUg/mL/h and 36.2 MUg/mL/h
      for Enro-Roral and Enro-Coral, respectively, and 8.55 +/- 0.85 MUg/mL/h and 56.4
      +/- 6.21 MUg/mL/h after IM administration of Enro-R and Enro-C, respectively. The
      PK/PD ratios and Monte Carlo simulations obtained with Enro-C, not Enro-R,
      indicated that its IM administration to dogs will result in therapeutic
      concentrations appropriate for treating leptospirosis. This is the first time
      enrofloxacin has been recommended to treat this disease in dogs.

PMID- 29649859
TI  - Comparison of electrophysiological properties of two types of pre-sympathetic
      neurons intermingled in the hypothalamic paraventricular nucleus.
AB  - The hypothalamic paraventricular nucleus (PVN) contains two types of neurons
      projecting to either the rostral ventrolateral medulla (PVNRVLM) or the
      intermediolateral horn (IML) of the spinal cord (PVNIML). These two neuron groups
      are intermingled in the same subdivisions of the PVN and differentially regulate
      sympathetic outflow. However, electrophysiological evidence supporting such
      functional differences is largely lacking. Herein, we compared the
      electrophysiological properties of these neurons by using patch-clamp and
      retrograde-tracing techniques. Most neurons (>70%) in both groups spontaneously
      fired in the cell-attached mode. When compared to the PVNIML neurons, the PVNRVLM
      neurons had a lower firing rate and a more irregular firing pattern (p < 0.05).
      The PVNRVLM neurons showed smaller resting membrane potential, slower rise and
      decay times, and greater duration of spontaneous action potentials (p < 0.05).
      The PVNRVLM neurons received greater inhibitory synaptic inputs (frequency, p <
      0.05) with a shorter rise time (p < 0.05). Taken together, the results indicate
      that the two pre-sympathetic neurons differ in their intrinsic and extrinsic
      electrophysiological properties, which may explain the lower firing activity of
      the PVNRVLM neurons. The greater inhibitory synaptic inputs to the PVNRVLM
      neurons also imply that these neurons have more integrative roles in regulation
      of sympathetic activity.

PMID- 29649860
TI  - Identification of determinants that mediate binding between Tembusu virus and the
      cellular receptor heat shock protein A9.
AB  - Heat shock protein A9 (HSPA9), a member of the heat shock protein family, is a
      putative receptor for Tembusu virus (TMUV). By using Western blot and co
      immunoprecipitation assays, E protein domains I and II were identified as the
      functional domains that facilitate HSPA9 binding. Twenty-five overlapping
      peptides covering domain I and domain II sequences were synthesized and analyzed
      by using an HSPA9 binding assay. Two peptides showed the capability of binding to
      HSPA9. Dot blot assay of truncated peptides indicated that amino acid residues 19
      to 22 and 245 to 252 of E protein constitute the minimal motifs required for TMUV
      binding to HSPA9. Importantly, peptides harboring those two minimal motifs could
      effectively inhibit TMUV infection. Our results provide insight into TMUV
      receptor interaction, thereby creating opportunities for elucidating the
      mechanism of TMUV entry.

PMID- 29649861
TI  - A Systematic Review of Benefit of Silicone Intubation in Endoscopic
      Dacryocystorhinostomy.
AB  - OBJECTIVES: Insertion of a silicone stent during endoscopic dacryocystorhinostomy
      (DCR) is the most common procedure to prevent rhinostomy closure. It has been
      claimed that silicone intubation improves the surgical outcomes of endoscopic
      DCR. However, many reports have documented an equally high success rate for
      surgery without silicone intubation. Accordingly, we conducted a systematic
      review and meta-analysis to clarify the outcomes of endoscopic DCR with and
      without silicone intubation and determine whether silicone intubation is actually
      beneficial for patients. METHODS: PubMed, Embase, and Cochrane Library databases
      were searched to identify relevant controlled trials evaluating endoscopic DCR
      with and without silicone intubation. The search was restricted to English
      articles published between January 2007 and December 2016. Relevant articles were
      reviewed to obtain information pertaining to interventions and outcomes. We also
      performed a meta-analysis of the relevant literature. RESULTS: In total, 1,216
      patients included in 12 randomized controlled trials were pooled. A total of
      1,239 endoscopic DCR procedures were performed, and silicone stents were used in
      533 procedures. The overall success rate for endoscopic DCR was 91.9%
      (1,139/1,239), while the success rates with and without silicone intubation were
      92.9% (495/533) and 91.2% (644/706), respectively. There was no statistically
      significant heterogeneity among the included studies. A meta-analysis using a
      fixed-effects models showed no significant difference in the success rate between
      endoscopic DCR with silicone intubation and that without silicone intubation (OR,
      1.38; 95% CI, 0.89 to 2.12; P=0.148; z=1.45). Furthermore, there were no
      significant differences with regard to surgical complications such as synechia,
      granulation, and postoperative bleeding. CONCLUSION: The findings of our meta
      analysis suggest that the success rate and postoperative complication rate for
      endoscopic DCR is not influenced by the use of silicone intubation during the
      procedure.

PMID- 29649863
TI  - New Taste-Active 3-( O-beta-d-Glucosyl)-2-oxoindole-3-acetic Acids and
      Diarylheptanoids in Cimiciato-Infected Hazelnuts.
AB  - Activity-guided fractionation in combination with sensory analytics, LC-TOF-MS,
      and 1D/2D-NMR spectroscopy enabled the identification of the bitter tasting
      diarylheptanoids asadanin, giffonin P, and the previously not reported ( E)
      7,9,10,13-tetrahydroxy-1,7-bis(2-hydroxyphenyl)hept-9-en-11-one and 4,12,16
      trihydroxy-2-oxatricyclo[13.3.1.13,7]-nonadeca-1(18),3,5,7(20),8,15,17-heptaen as
      well as the yet unknown astringent compounds 2-(3-hydroxy-2-oxoindolin-3-yl)
      acetic acid 3- O-6'-galactopyranosyl-2"-(2"oxoindolin-3"yl) acetate and 3-( O
      beta-d-glycosyl) dioxindole-3-acetic acid in Cimiciato-infected hazelnuts
      exhibiting a bitter off-taste. Quantitative LC-MS/MS studies, followed by
      dose/activity considerations confirmed for the first time asadanin to be the key
      contributor to the bitter taste of Cimiciato-infected hazelnuts. Furthermore,
      quantitative studies demonstrated that neither the physical damage alone nor a
      general microbial infection is able to initiate a stress-induced asadanin
      generation, but most likely either specific Cimiciato-specific microorganisms
      associated with the bugs or specific chemical stimulants in the bugs' saliva is
      the cause triggering asadanin biosynthesis. Finally, also germination was found
      for the first time to activate diarylheptanoid biosynthesis, resulting in higher
      contents of bitter tasting phytochemicals and development of the bitter off
      taste.

PMID- 29649864
TI  - Use of Mercury Isotopes to Quantify Mercury Exposure Sources in Inland
      Populations, China.
AB  - Mercury (Hg) isotopic compositions in hair and dietary sources from Wanshan (WS)
      Hg mining area, Guiyang (GY) urban area, and Changshun (CS) rural area were
      determined to identify the major Hg exposure sources of local residents. Rice and
      vegetables displayed low delta202Hg and small negative to zero Delta199Hg, and
      are isotopically distinguishable from fish which showed relatively higher
      delta202Hg and positive Delta199Hg. Distinct isotopic signatures were also
      observed for human hair from the three areas. Shifts of 2 to 30/00 in delta202Hg
      between hair and dietary sources confirmed mass dependent fractionation of Hg
      isotopes occurs during metabolic processes. Near zero Delta199Hg of hair from WS
      and CS suggested rice is the major exposure source. Positive Delta199Hg of hair
      from GY was likely caused by consumption of fish. A binary mixing model based on
      Delta199Hg showed that rice and fish consumption accounted for 59% and 41% of
      dietary Hg source for GY residents, respectively, whereas rice is the major
      source for WS and CS residents. The model output was validated by calculation of
      probable daily intake of Hg. Our study suggests that Hg isotopes can be a useful
      tracer for quantifying exposure sources and understanding metabolic processes of
      Hg in humans.

PMID- 29649866
TI  - A Plasticizer-Free Miniaturized Optical Ion Sensing Platform with Ionophores and
      Silicon-Based Particles.
AB  - Nanoscale ionophore-based ion-selective optodes (nano-ISOs) are effective sensing
      tools for in situ and real time measurements of ion concentrations in biological
      and environmental samples. While searching for novel sensing materials, nano-ISOs
      free of plasticizers are particularly important for biological and environmental
      applications. This work described plasticizer-free nano-ISOs based on Si
      containing particles including PEGylated organosilica nanoparticles, PDMS
      nanospheres, and SiO2 microspheres, with diameters around 50 nm, 100 nm, and 5
      MUm, respectively. The platform enabled the use of highly selective ionophores,
      where the nanomatrices played important roles in tuning the ion-carrier complex
      formation constants and led to better selectivity for the PEGylated organosilica
      nano-ISOs than those based on PDMS. With use of the versatile silica chemistry,
      pH and ion dual sensing was achieved on SiO2 microspheres. In addition,
      increasing the cross-linking degree of the PDMS nano-ISOs extended the linear
      response range, and cellular uptake experiments showed that the nano-ISOs could
      readily enter HeLa cells with very low cytotoxicity.

PMID- 29649865
TI  - Sb2Te3 and Its Superlattices: Optimization by Statistical Design.
AB  - The objective of this work is to demonstrate the usefulness of fractional
      factorial design for optimizing the crystal quality of chalcogenide van der Waals
      (vdW) crystals. We statistically analyze the growth parameters of highly c axis
      oriented Sb2Te3 crystals and Sb2Te3-GeTe phase change vdW heterostructured
      superlattices. The statistical significance of the growth parameters of
      temperature, pressure, power, buffer materials, and buffer layer thickness was
      found by fractional factorial design and response surface analysis. Temperature,
      pressure, power, and their second-order interactions are the major factors that
      significantly influence the quality of the crystals. Additionally, using tungsten
      rather than molybdenum as a buffer layer significantly enhances the crystal
      quality. Fractional factorial design minimizes the number of experiments that are
      necessary to find the optimal growth conditions, resulting in an order of
      magnitude improvement in the crystal quality. We highlight that statistical
      design of experiment methods, which is more commonly used in product design,
      should be considered more broadly by those designing and optimizing materials.

PMID- 29649867
TI  - Excellent NiO-Ni Nanoplate Microwave Absorber via Pinning Effect of
      Antiferromagnetic-Ferromagnetic Interface.
AB  - Materials with strong magnetic property that can provide excellent microwave
      absorption performance are highly desirable, especially if their dielectric and
      magnetic properties can be easily modulated, which make minimal thickness and
      ultrawide bandwidth become achievable. The magnetic properties of ferromagnetic
      (FM) and antiferromagnetic (AFM) composite materials are closely related to their
      ratio of composition, size, morphology, and structure. AFM-FM composites have
      become a popular alternative for microwave absorption; however, the controllable
      design and preparation need to be urgently optimized. Here, we have successfully
      prepared a series of platelike NiO-Ni composites and demonstrated the potential
      of such composites for microwave absorption. Strong magnetic coupling was found
      from NiO-Ni nanoparticles by electron holography, which makes NiO-Ni composites a
      highly efficient microwave absorber (strong reflection loss: -61.5 dB and broad
      bandwidth: 11.2 GHz, reflection loss < -10 dB). Our findings are helpful to
      develop a strong microwave absorber based on magnetic coupling.

PMID- 29649868
TI  - Hybrid Black Phosphorus/Zero-Dimensional Quantum Dot Phototransistors: Tunable
      Photodoping and Enhanced Photoresponsivity.
AB  - Recently, black phosphorus (BP) with direct band gap exhibited excellent
      potential for optoelectronic applications because of its high charge carrier
      mobility and low dark current as well as the variable band gap of 0.3-1.5 eV
      depending on the number of layers. However, few-layer BP-based phototransistors
      (photo-FETs) have been limited in sensitivity and wavelength selectivity. To
      overcome the drawback of these photo-FETs, we studied hybrid photo-FETs combined
      with the novel properties of the two materials between the channel and sensitizer
      layers. By combining a strong absorbance of a quantum dot (QD) layer and a two
      dimensional layer material with high carrier mobility, the hybrid photo-FETs are
      expected to produce high-performance photodetectors that can effectively control
      the responsivity, detectivity, and response time. In this study, we demonstrate
      that the photogenerated carriers formed from QD sensitizer layers migrate to the
      BP transport layer with high charge mobility and not only improve the
      photodetector performance but also enhance the photodoping effect of the BP
      transport layer with an ambipolar characteristic by electrons transferred from n
      type CdSe QDs or holes injected from p-type PbS QDs. The responsivity and
      detectivity of hybrid BP/0D photo-FETs exhibit 1.16 * 109 A W-1 and 7.53 * 1016
      Jones for the BP/CdSe QD photo-FET and 5.36 * 108 A W-1 and 1.89 * 1016 Jones for
      the BP/PbS QD photo-FET, respectively. The photocurrent rise (taurise) and decay
      (taudecay) times were taurise = 0.406 s and taudecay = 0.815 s for BP/CdSe QD
      photo-FET and taurise = 0.576 s and taudecay = 0.773 s for BP/PbS QD photo-FET,
      respectively.

PMID- 29649869
TI  - Floating and Tether-Coupled Adhesion of Bacteria to Hydrophobic and Hydrophilic
      Surfaces.
AB  - Models for bacterial adhesion to substratum surfaces all include uncertainty with
      respect to the (ir)reversibility of adhesion. In a model, based on vibrations
      exhibited by adhering bacteria parallel to a surface, adhesion was described as a
      result of reversible binding of multiple bacterial tethers that detach from and
      successively reattach to a surface, eventually making bacterial adhesion
      irreversible. Here, we use total internal reflection microscopy to determine
      whether adhering bacteria also exhibit variations over time in their
      perpendicular distance above surfaces. Streptococci with fibrillar surface
      tethers showed perpendicular vibrations with amplitudes of around 5 nm,
      regardless of surface hydrophobicity. Adhering, nonfibrillated streptococci
      vibrated with amplitudes around 20 nm above a hydrophobic surface. Amplitudes did
      not depend on ionic strength for either strain. Calculations of bacterial
      energies from their distances above the surfaces using the Boltzman equation
      showed that bacteria with fibrillar tethers vibrated as a harmonic oscillator.
      The energy of bacteria without fibrillar tethers varied with distance in a
      comparable fashion as the DLVO (Derjaguin, Landau, Verwey, and Overbeek)
      interaction energy. Distance variations above the surface over time of bacteria
      with fibrillar tethers are suggested to be governed by the harmonic oscillations,
      allowed by elasticity of the tethers, piercing through the potential energy
      barrier. Bacteria without fibrillar tethers "float" above a surface in the
      secondary energy minimum, with their perpendicular displacement restricted by
      their thermal energy and the width of the secondary minimum. The distinction
      between "tether-coupled" and "floating" adhesion is new, and may have
      implications for bacterial detachment strategies.

PMID- 29649870
TI  - Oxygen- and Water-Induced Energetics Degradation in Organometal Halide
      Perovskites.
AB  - Organometal halide perovskites are under rapid development, and significant focus
      has been placed on their stability that currently presents a major obstacle for
      practical application. Energetics plays a vital role in charge
      injection/extraction and transport properties in devices. Here, we in situ
      investigate oxygen- and water-induced energetics degradation in organometal
      halide perovskite films. Oxygen gas induces an upward shift of the vacuum level
      of the perovskite films because of the formation of an oxygen-induced surface
      dipole, water vapor causes a significant vacuum-level downshift, and the valence
      band binding energy referenced to the Fermi level simultaneously increases so as
      to keep the ionization potential of the perovskite films unchanged. Moreover, the
      chemical compositions, crystalline structures, surface morphologies, and
      dynamical properties also are monitored and analyzed in detail. These results are
      indispensable to understand the degradation mechanisms and to perform the
      optimizations of stable materials and devices in the future.

PMID- 29649871
TI  - High-Pressure Evolution of Crystal Bonding Structures and Properties of FeOOH.
AB  - Recent conflicting reports on the high-pressure structural evolution of iron
      oxide-hydroxide (FeOOH) offer starkly contrasting scenarios for the hydrogen and
      oxygen cycles in Earth's interior. Here we explore the crystal structures of
      FeOOH using an advanced search algorithm combined with first-principles
      calculations. Our results indicate a phase transition around 70 GPa from the
      known epsilon-FeOOH to a new pyrite-type FeOOH (P-FeOOH) phase, and the two
      phases remain nearly degenerate in an unusually large pressure range. These
      findings clarify and explain the experimentally observed structural evolution and
      extensive phase coexistence. Moreover, our structure search identifies a
      previously unknown monoclinic (M-FeOOH) phase that is energetically close to P
      FeOOH at pressures near the core-mantle boundary. We further reveal that the high
      pressure FeOOH phases exhibit remarkably distinct sound-velocity profiles,
      providing key material properties essential to interpreting seismic data and
      elucidating FeOOH's influence on geophysical and geochemical processes in deep
      Earth.

PMID- 29649872
TI  - First-Principles Investigation of the Formation of Pt Nanorafts on a Mo2C Support
      and Their Catalytic Activity for Oxygen Reduction Reaction.
AB  - We use first-principles calculations to study the formation of Pt nanorafts and
      their oxygen reduction reaction (ORR) catalytic activity on Mo2C. Due to the high
      Pt binding energy on C atoms, Pt forms sheet-like structures on the Mo2C surface
      instead of agglomerating into particles. We find that the disordered Mo2C surface
      carbon arrangement limits the Pt sheet growth, leading to the formation of 4-6
      atom Pt nanorafts. The O-O repulsion between the O atoms on the Mo2C and O
      adsorbate enhances the ORR activity by weakening the O adsorption energy. We find
      a significant change from the usual scaling of the energies of the intermediates
      in the ORR pathway and a strong interaction between the nanoraft and water that
      lead to a high activity of the Pt nanorafts. Fundamentally, our work demonstrates
      that the activity of metal catalysts can be strongly affected by manipulation of
      the atomic arrangement of the supporting carbide surface.

PMID- 29649873
TI  - pH Dependency in Anode Biofilms of Thermincola ferriacetica Suggests a Proton
      Dependent Electrochemical Response.
AB  - Monitoring the electrochemical response of anode respiring bacteria (ARB) helps
      elucidate the fundamental processes of anode respiration and their rate
      limitations. Understanding these limitations provides insights on how ARB create
      the complex interfacing of biochemical metabolic processes with insoluble
      electron acceptors and electronics. In this study, anode biofilms of the
      thermophilic (60  degrees C) Gram-positive ARB Thermincola ferriacetica were
      studied to determine the presence of a proton-dependent electron transfer
      response. The effects of pH, the presence of an electron donor (acetate), and
      biofilm growth were varied to determine their influence on the electrochemical
      midpoint potential ( EKA) and formal redox potential ( E degrees ') under
      nonturnover conditions. The EKA and E degrees ' are associated with an enzymatic
      process within ARB's metabolism that controls the rate and energetic state of
      their respiration. Results for all conditions indicate that pH was the major
      contributor to altering the energetics of T. ferriacetica anode biofilms.
      Electrochemical responses measured in the absence of an electron donor and with a
      minimal proton gradient within the anode biofilms resulted in a 48 +/- 7 mV/pH
      unit shift in the E degrees ', suggesting a proton-dependent rate-limiting
      process. Given the limited energy available for anode respiration (<200 mV when
      using acetate as electron donor), our results provide a new perspective in
      understanding proton-transport limitations in ARB biofilms, one in which ARB are
      thermodynamically limited by pH gradients. Since the anode biofilms of all ARB
      that perform direct extracellular electron transfer (EET) investigated thus far
      exhibit an n = 1 Nernstian behavior, and because this behavior is affected by
      changes in pH, we hypothesize that the Nernstian response is associated with
      membrane proteins responsible for proton translocation. Finally, this study shows
      that the EKA and E degrees ' are a function of pH within the physiological range
      of ARB, and thus, given the significant effect pH has on this parameter, we
      recommend reporting the EKA and E degrees ' of ARB biofilms at a specific bulk
      pH.

PMID- 29649874
TI  - Structural Dynamics of the Oxygen-Evolving Complex of Photosystem II in Water
      Splitting Action.
AB  - Oxygenic photosynthesis in nature occurs via water splitting catalyzed by the
      oxygen-evolving complex (OEC) of photosystem II. To split water, the OEC cycles
      through a sequence of oxidation states (S i, i = 0-4), the structural mechanism
      of which is not fully understood under physiological conditions. We monitored the
      OEC in visible-light-driven water-splitting action by using in situ, aqueous
      environment surface-enhanced Raman scattering (SERS). In the unexplored low
      frequency region of SERS, we found dynamic vibrational signatures of water
      binding and splitting. Specific snapshots in the dynamic SERS correspond to
      intermediate states in the catalytic cycle, as determined by density functional
      theory and isotopologue comparisons. We assign the previously ambiguous
      protonation configuration of the S0-S3 states and propose a structural mechanism
      of the OEC's catalytic cycle. The findings address unresolved questions about
      photosynthetic water splitting and introduce spatially resolved, low-frequency
      SERS as a chemically sensitive tool for interrogating homogeneous catalysis in
      operando.

PMID- 29649875
TI  - Doubly pH Responsive Emulsions by Exploiting Aggregation of Oppositely Charged
      Nanoparticles and Polyelectrolytes.
AB  - We present a simple and modular approach to realize highly stable pH responsive
      Pickering emulsion from mixtures of commercially available oppositely charged
      nanoparticle and polyelectrolyte. While highly charged nanoparticles and
      polyelectrolytes when used solely do not stabilize emulsions, we show that the
      electrostatic attraction between oppositely charged nanoparticles and
      polyelectrolytes can be exploited to formulate emulsions with long-term stability
      of up to 8 months. The Ludox CL nanoparticles and poly(4-styrenesulfonate) sodium
      salt (PSS) when dispersed in aqueous solution at pH 2-11 form particle
      polyelectrolyte complexes (PPCs) due to heteroaggregation. These complexes are
      effective in stabilizing oil-in-water Pickering emulsions. We demonstrate that
      this is due to the formation of weakly charged complexes that are surface active
      and hence readily adsorbed to the oil-water interface created during
      emulsification. We show that the composition of nanoparticles and
      polyelectrolytes in the mixture as well as the pH can be tuned to control the
      average diameter of the emulsions droplets. Immediate destabilization and doubled
      responsiveness of the emulsions stabilized by particle polyelectrolyte complexes
      are illustrated by changing the pH of the stable emulsions formed at intermediate
      pH to either 1 or 13. The aggregation behavior of nanoparticle-polyelectrolyte
      mixtures and the effect of various parameters such as mixing fraction, pH, and
      energy input on the formation of Pickering emulsions is discussed. Furthermore,
      we show that the formation of near charge neutral aggregates that exhibit optimal
      wetting conditions is a requirement to accomplish emulsion formation. The
      visualization of particle polyelectrolyte complexes around the emulsion droplets,
      their morphology prior to emulsification, and their wetting properties are also
      investigated to elucidate the mechanism of emulsification.

PMID- 29649877
TI  - beta- N-Methylamino-l-alanine (BMAA) Not Involved in Alzheimer's Disease.
AB  - beta- N-Methylamino-l-alanine (BMAA) is a neurotoxic agent implicated in ALS as
      well as Parkinson's and Alzheimer's diseases. It is produced by blue-green algae
      and could find its way via fish and seafood into the human food supply. Isolation
      from biological samples yields the compound in monomeric and protein-bound form.
      It has been suggested that the protein-bound fraction may result from genetic
      misincorporation into proteins in place of serine. Concomitant misfolding of the
      mutated proteins may be responsible for the neurological diseases. Recent reports
      that contradict the misincorporation theory leave unresolved the nature of the
      protein-bound form of BMAA. We have found from quantum mechanical calculations on
      model systems that it is possible to bind BMAA with high affinity in a
      noncovalent fashion to proteins. Because of our interest in Alzheimer's disease,
      molecular dynamics simulations were applied to search for such binding between
      BMAA and the beta-amyloid peptide and to discover whether replacement of either
      of its two serine residues could affect its aggregation into neurotoxic
      oligomers. No stable noncovalently bound complex was found, and it was concluded
      that incorporation of BMAA in place of serine would not alter the conformational
      dynamics of the beta-amyloid peptide.

PMID- 29649876
TI  - Biomolecular Simulations under Realistic Macroscopic Salt Conditions.
AB  - Biomolecular simulations are typically performed in an aqueous environment where
      the number of ions remains fixed for the duration of the simulation, generally
      with either a minimally neutralizing ion environment or a number of salt pairs
      intended to match the macroscopic salt concentration. In contrast, real
      biomolecules experience local ion environments where the salt concentration is
      dynamic and may differ from bulk. The degree of salt concentration variability
      and average deviation from the macroscopic concentration remains, as yet,
      unknown. Here, we describe the theory and implementation of a Monte Carlo
      osmostat that can be added to explicit solvent molecular dynamics or Monte Carlo
      simulations to sample from a semigrand canonical ensemble in which the number of
      salt pairs fluctuates dynamically during the simulation. The osmostat reproduces
      the correct equilibrium statistics for a simulation volume that can exchange ions
      with a large reservoir at a defined macroscopic salt concentration. To achieve
      useful Monte Carlo acceptance rates, the method makes use of nonequilibrium
      candidate Monte Carlo (NCMC) moves in which monovalent ions and water molecules
      are alchemically transmuted using short nonequilibrium trajectories, with a
      modified Metropolis-Hastings criterion ensuring correct equilibrium statistics
      for an ( DeltaMU, N, p, T) ensemble to achieve a ~1046* boost in acceptance
      rates. We demonstrate how typical protein (DHFR and the tyrosine kinase Src) and
      nucleic acid (Drew-Dickerson B-DNA dodecamer) systems exhibit salt concentration
      distributions that significantly differ from fixed-salt bulk simulations and
      display fluctuations that are on the same order of magnitude as the average.

PMID- 29649879
TI  - Special Issue on Drug Discovery for Global Health.

PMID- 29649878
TI  - 2nd SCI/RSC Symposium on Medicinal Chemistry for Global Health: A Unique
      Opportunity for the Field.

PMID- 29649880
TI  - Pulmonary inflammatory myofibroblastic tumor: a case report.
AB  - Pulmonary inflammatory myofibroblastic tumor is a rare disease. Computed
      tomography in a 54-year-old woman showed a mass compressing the segmental
      bronchus of the left lung. Bronchoscopy indicated a mesenchymal tumor, hamartoma,
      or inflammatory myofibroblastic tumor. Because an inflammatory myofibroblastic
      tumor can potentially clog the segmental bronchus, we performed a left upper
      division segmentectomy. Pathologic examination revealed an inflammatory
      myofibroblastic tumor. In most cases, preoperative diagnosis is difficult because
      of the varied radiologic manifestations, and it can also be difficult to
      distinguish from malignancy in small tissue samples.

PMID- 29649881
TI  - Dual drainage total anomalous pulmonary venous connection: a rare mixed variant.
AB  - The mixed type of total anomalous pulmonary venous connection is the least common
      variant, occurring in approximately 5% of all patients. Dual drainage through a
      common venous confluence is much rarer. Computed tomography to delineate the
      exact pulmonary venous anatomy is a must in such cases. Correct preoperative
      recognition and intraoperative confirmation to check the drainage of all 4
      pulmonary veins is essential in all cases of total anomalous pulmonary venous
      connection. We report the case of an adult patient with dual drainage to coronary
      sinus and left vertical vein to innominate vein.

PMID- 29649882
TI  - Local Atopy in Childhood Adenotonsillar Hypertrophy.
AB  - Background Although the cause of adenotonsillar hypertrophy remains unknown, some
      studies have shown that allergy may be a risk factor. Purpose This study
      determined the levels of allergen-specific immunoglobulin E (sIgE) in the
      adenotonsillar tissues of children with adenotonsillar hypertrophy and evaluated
      the clinical significance of local atopy in adenotonsillar tissues. Methods We
      measured 21 types of specific immunoglobulin E in the serum and adenotonsillar
      tissues of 102 children with adenotonsillar hypertrophy and compared the
      sensitization patterns of the serum and local tissues. The patients were divided
      into three groups-atopy, local atopy, and nonatopy-according to the sensitization
      of serum and adenotonsillar tissues, and the clinical symptoms among the groups
      were analyzed. Results Seventy-two (70.6%) children with adenotonsillar
      hypertrophy were sensitized to more than one allergen in the serum and/or
      adenotonsillar tissue. Thirty (29.4%) children had no IgE positivity to any
      allergen in both serum and adenotonsillar tissues. Fifty-five (53.9%) were
      sensitized to at least one allergen in the serum. Seventy (68.6%) were sensitized
      to at least one allergen in the adenotonsillar tissue. Seventeen (36.2%) of 47
      children with specific immunoglobulin E-negative serum had specific
      immunoglobulin E-positive adenotonsillar tissues. The rate of specific
      immunoglobulin E was significantly higher in local tissues than in serum. The
      rate of inhalant allergen specific immunoglobulin E was significantly higher in
      the adenoids than in the tonsils. However, the rate of food allergen specific
      immunoglobulin E was significantly higher in the tonsils than adenoids. The
      lifetime prevalence of asthma and allergic rhinitis, recent symptoms or treatment
      of allergic rhinitis, and severity of nasal symptoms (rhinorrhea, sneezing, and
      nasal itching) were significantly higher in children with local atopy than with
      nonatopy. Conclusions These results confirm that allergic response may be a risk
      factor for adenotonsillar hypertrophy. Local allergic inflammation may play an
      important role in childhood adenotonsillar hypertrophy, and local atopy in
      adenotonsillar tissues can cause respiratory allergic symptoms in children.

PMID- 29649883
TI  - Role of Geographic Information System in Assessing Determinants of Cardiovascular
      Disease: An Experience From a Low- and Middle-Income Country.
AB  - Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in
      the world. The determinants of CVD in an urban population using conventional and
      geographic information system techniques were attempted as a community-based
      census-type cross-sectional study in Kerala, India, among 1649 individuals
      residing in 452 households. Sociodemographic details, risk factor exposures, and
      self-reported disease prevalence were determined. Location of houses, wells from
      which subjects drew drinking water, and distances of the house from the outer
      road (proxy for air pollution) were mapped using differential global positioning
      system and pH of water samples determined. Prevalence of CVD was 5.8%.
      Significant predictors of CVD were male gender, diabetes mellitus, hypertension,
      and hypothyroidism. Statistically significant spatial association was found
      between CVD and groundwater pH. Geographic information system technology is
      useful in identification of spatial clustering and disease hotspots for designing
      preventive strategies targeting CVD.

PMID- 29649884
TI  - The Pharmacologic Role and Clinical Utility of PCSK9 Inhibitors for the Treatment
      of Hypercholesterolemia.
AB  - In addition to monoclonal antibodies against proprotein convertase subtilisin
      kexin type 9 (PCSK9), vaccines against PCSK9 and smaller molecule inhibitors as
      well as RNA inhibitors of PCSK9 production have been created. The monoclonal
      antibodies against PCSK9 and the PCSK9 RNA inhibitors can reduce low-density
      lipoproteins (LDLs) by over 50%, non-high-density lipoprotein (HDL) cholesterol
      and triglycerides, and increasing HDL. Although effective in several homozygous
      familial hypercholesterolemia patient types, PCSK9 inhibitors does not work in
      all patient types. Outcome trials show no effects on mortality but do show
      reductions in atherosclerotic events such as myocardial infarctions, strokes, and
      need for coronary revascularization. PCSK9 inhibitors have a very attractive
      safety profile with no significant elevations in measures of muscle or liver
      damage. The current and more advanced experimental agents all require
      subcutaneous dosing, and injection site reactions are among the most common
      adverse events. Therapy for the Food and Drug Administration (FDA) approved
      agents is markedly expensive, and this is the primary barrier to utilization.
      However, it is possible to identify patients with a number needed to treat to
      prevent an atherosclerotic event low enough to render it cost-effective and one
      such factor is whether or not you require a 50% reduction in LDL in order to
      achieve your LDL goal.

PMID- 29649885
TI  - Efficacy and Safety of S-Amlodipine 2.5 and 5 mg/d in Hypertensive Patients Who
      Were Treatment-Naive or Previously Received Antihypertensive Monotherapy.
AB  - The aim of the present study was to evaluate the efficacy and safety of S
      amlodipine 2.5 and 5 mg/d in patients with hypertension who were treatment-naive
      or previously received antihypertensive monotherapy. During the 8-week treatment
      period, all patients received S-amlodipine 2.5 mg/d for the first 4 weeks,
      followed by S-amlodipine 5 mg/d for the second 4 weeks. For efficacy assessments,
      ambulatory and office blood pressure (BP) measurements were performed during the
      baseline, fourth-week, and eighth-week visits. For safety assessments, all
      adverse events and abnormal laboratory findings were recorded. This study is
      registered with ClinicalTrials.gov (NCT03038451). Of 43 patients evaluated at the
      screening visit, 33 were enrolled. In the treatment-naive arm, significant
      reductions in both office and ambulatory systolic BP (SBP) and diastolic BP (DBP)
      were observed with S-amlodipine 2.5 mg/d and additional significant reductions
      were achieved with dose titration (S-amlodipine 5 mg/d). At the end of the study,
      the rate of the treatment-naive patients with BP under control (SBP/DBP <140/90
      mm Hg) was 53% with S-amlodipine 2.5 mg and increased to 78% with S-amlodipine 5
      mg. For the noninferiority evaluation, S-amlodipine 2.5 and 5 mg/d treatments
      were generally noninferior to both office and ambulatory BP levels achieved with
      the medications that the patients received before participating in the study.
      Five nonserious adverse events likely to be associated with the study drug were
      observed. No serious adverse event was encountered. Consequently, S-amlodipine
      can be suggested as an effective and safe treatment option for patients with
      hypertension.

PMID- 29649886
TI  - Cultural Adaptations to the Measurement of Attitudes to Ageing: Psychometric
      Assessment of the Malay Reactions to Ageing Questionnaire.
AB  - The aims of this study were to culturally adapt the Reactions to Ageing
      Questionnaire (RAQ) for a non-Western (Malay) population, and explore attitudes
      to ageing in relation to age, gender, and education. Eight new culturally
      relevant items were generated by asking Malay-speaking participants about their
      reactions to ageing. A Malay version of the extended 35-item RAQ was then
      administered to 911 Malaysian participants aged 18 to 60 years. Exploratory
      factor analysis revealed four factors. Three of the factors were similar to those
      identified in the original RAQ, while "Family and Religion" emerged as a new
      factor. More negative attitudes to ageing were observed in younger and female
      respondents. There were no effects of education. This culturally adapted RAQ
      exhibits robust psychometric properties, and could be used to assess attitudes to
      ageing in Malaysia and other Southeast Asian countries. Moreover, we have
      identified a "core set" of RAQ items that could be applicable worldwide.

PMID- 29649887
TI  - Clinical Effect of Endoscopic Vidian Neurectomy on Bronchial Asthma Outcomes in
      Patients with Coexisting Refractory Allergic Rhinitis and Asthma.
AB  - Background The prevalence of both allergic rhinitis and bronchial asthma is high
      throughout the world; their mutual influence on each other has been documented in
      many studies. However, studies regarding surgical intervention are limited.
      Objective To evaluate the clinical significance of endoscopic vidian neurectomy
      on bronchial asthma outcomes in patients with coexisting refractory allergic
      rhinitis and asthma. Methods A total of 109 patients with moderate to severe
      persistent intractable allergic rhinitis and mild/moderate asthma were allocated
      to the bilateral endoscopic vidian neurectomy group (group 1) or conservative
      medication group (group 2) according to the patients' self-selection. The
      Rhinoconjunctivitis Quality of Life Questionnaire, Visual Analog Scale, Asthma
      Quality of Life Questionnaire, Total Asthma Symptom Score, and medication scores
      were evaluated at six months, one year, and three years after undergoing the
      initial treatments. Multivariate analysis was performed to determine which
      triggers of asthma attacks were associated with improved asthma outcomes in
      patients. Results Ninety-five patients were followed up for at least three years.
      Postoperative scores of Rhinoconjunctivitis Quality of Life Questionnaire and
      Visual Analog Scale were significantly lower than preoperative scores during
      follow-up in group 1 and were significantly lower than those of group 2.
      Postoperative scores of Asthma Quality of Life Questionnaire at the three follow
      up time points were higher than the preoperative scores in group 1. The Total
      Asthma Symptom Score was not significantly decreased in group 1. The medication
      scores for allergic rhinitis and asthma were gradually reduced after surgery. At
      the end of the follow-up, the improvement rates for allergic rhinitis and asthma
      were 90.6% and 45.3%, respectively. Asthma outcomes were significantly improved
      by controlling rhinitis symptoms in patients whose asthma attacks were induced by
      "rhinitis onset" or "weather change." Conclusion Controlling allergic rhinitis
      symptoms by bilateral endoscopic vidian neurectomy can significantly improve
      asthma outcomes in patients whose asthma attacks are induced by rhinitis onset
      and/or cold air.

PMID- 29649888
TI  - Factors affecting occupational therapists' decision to join their regional
      professional association: Facteurs influencant la decision des ergotherapeutes de
      joindre les rangs de leur association professionnelle regionale.
AB  - BACKGROUND: Voluntary occupational therapy organizations fill an important role.
      However, recruitment and retention can be problematic. Little is known about
      factors influencing occupational therapists to join/maintain membership in
      professional associations. PURPOSE: This study investigated factors influencing
      occupational therapists' decision to join/remain members of their association.
      METHOD: An electronic survey was carried out and data were analyzed using SPSS
      software and manual categorization of open-ended comments. FINDINGS: Two hundred
      and fifty-four therapists responded. Generation of new ideas, opportunities for
      professional development, self-improvement, maintenance of standards, improvement
      of the profession, and discounts on equipment/educational opportunities were
      significant factors in deciding to join the organization. The factors perceived
      as priorities varied in relation to participants' year of graduation.
      IMPLICATIONS: More-customized strategies, reflecting priorities that vary during
      a therapist's career path, may need to be employed to best address recruitment
      and retention across the range of therapists' needs and goals.

PMID- 29649889
TI  - Endoscopic Resection of Sinonasal Inverted Papilloma: Systematic Review and Meta
      Analysis.
AB  - Background Pure endoscopic surgery (functional endoscopic sinus surgery) has been
      increasingly replacing external approaches in the management of sinonasal
      inverted papillomas. Objective To analyze and compare the effectiveness of pure
      endoscopic procedure with external or combined procedures to paranasal inverted
      papillomas, including the experience from two institutions in North Greece, over
      a 20-year period. Methods Systematic literature searches of MEDLINE (1952-2016),
      EMBASE (1974-2016), and the Cochrane Central Register of Controlled Trials.
      Review of all English-language studies comparing endoscopic and open techniques.
      Odds ratios (ORs), risk ratio, 95% confidence intervals (CIs), and tests for
      heterogeneity were reported. Recurrence rates according to initial tumor stage.
      Results In total, 2451 patients had been enrolled in the 23 studies, published
      between 1992 and 2014. All the included articles are graded as level IV evidence.
      Among the 1526 patients of the endoscopic group, 212 (13.8%) had recurrence, with
      the mean time of recurrence to range from 14 to 46.6 months. In the external
      approach group, 111 (18.7%) of the 592 patients had recurrence, with the time of
      recurrence to range from 7 to 92 months. The recurrence rate in the combined
      approach group was 12.9%. The occurrence rate of recurrence attributable to the
      surgical choice was significantly different between endoscopic and external group
      (OR: 0.61; 95% CI: 0.40-0.92; P = 0.02; 14.9% vs. 18.8% in endoscopic and
      external group, respectively). Conclusions The present systematic review and meta
      analysis indicates that endoscopic approach seems a favorable treatment option of
      sinonasal inverted papillomas and confirms the global recommendation that is the
      gold standard in the treatment of such nose lesions, revealing a lower recurrence
      rate compared to external approaches.

PMID- 29649891
TI  - Erratum.
AB  - Singer AE, Ash T, Ochotorena C, Lorenz KA, Chong K, Shreve ST, Ahluwalia SC. A
      Systematic Review of Family Meeting Tools in Palliative and Intensive Care
      Settings. Am J Hosp Palliat Care. 2016; 33(8):797-806. (DOI:
      10.1177/1049909115594353) It was noted that the following references were
      duplicated in the above mentioned article. (i) Billings JA, Block SD. The end-of
      life family meeting in intensive care part III: A guide for structured
      discussions. J Palliat Med. 2011;14(9):1058-1064. (ii) Fineberg IC, Kawashima M,
      Asch SM. Communication with families facing life-threatening illness: a research
      based model for family conferences. J Palliat Med. 2011;14(4):421-427. (iii)
      Curtis JR, Engelberg RA, Wenrich MD, Shannon SE, Treece PD, Rubenfeld GD. Missed
      opportunities during family conferences about end-of-life care in the intensive
      care unit . Am J Respir Crit Care Med. 2005;171(8):844-849. (iv) Lanken PN, Terry
      PB, Delisser HM, et al. An official American Thoracic Society clinical policy
      statement: palliative care for patients with respiratory diseases and critical
      illnesses . Am J Respir Crit Care Med. 2008;177(8):912-927. (v) Truog RD,
      Campbell ML, Curtis JR, et al. Recommendations for end-of-life care in the
      intensive care unit: a consensus statement by the American College of Critical
      Care Medicine. Crit Care Med. 2008;36(3):953-963. SAGE regrets the error.

PMID- 29649890
TI  - What Parenteral Opioids to Use in Face of Shortages of Morphine, Hydromorphone,
      and Fentanyl.
AB  - Parenteral potent opioid availability is becoming an issue in acute pain
      management. Two opioids, nalbuphine and buprenorphine, are available which can be
      substituted for hydromorphone, fentanyl, and morphine. There are advantages and
      disadvantages in using these 2 opioids which are discussed, and potential dosing
      strategies are outlined.

PMID- 29649892
TI  - A Pilot Comparison between Caregiver's and Patient's Perceived Quality of Life in
      Chronic Rhinosinusitis.
AB  - Introduction Chronic rhinosinusitis negatively impacts a patient's quality of
      life, but current studies only address the patient's perception of their disease.
      Caregivers living with the patient may have an alternative perception of the
      severity of the quality of life disturbance that patient's experience with
      chronic rhinosinusitis. Methods This was a prospective cohort study that enrolled
      patients with a confirmed chronic rhinosinusitis diagnosis who presented to
      clinic with a caregiver. At the initial visit, patients completed a
      Rhinosinusitis Disability Index. The caregiver completed a Rhinosinusitis
      Disability Index based on their perception of the patient's symptoms in addition
      to a Modified Caregiver Strain Index and a Short Form-36 to assess caregiving
      strain and overall health, respectively. Statistical analyses were performed with
      significance defined as P < 0.05 a priori. Results A total of 44 total subjects
      (22 patient and caregiver pairs) were enrolled. Patients reported a total
      Rhinosinusitis Disability Index of 36.8 (confidence interval: 26.9, 46.6), and
      caregivers reported a total Rhinosinusitis Disability Index of 50.4 [confidence
      interval: 38.8, 61.9] ( P = 0.02). The principal differences between patient and
      caregiver scores were noted in the emotional and physical domains ( P = 0.01 and
      P = 0.05, respectively). Only the functional domain was not statistically
      different ( P = 0.20). The patient's total Rhinosinusitis Disability Index is
      positively correlated with the caregiver's total Modified Caregiver Strain Index
      with a spearman coefficient of .60 (p <= 0.005). Conclusions Caregivers
      experience greater strain as the patient's quality of life declines. Caregivers
      perceive patients to have worse quality of life than patients report. Based on
      these data, caregivers may provide additional insight to the quality of life
      disturbance of chronic rhinosinusitis. In addition, the societal impact of
      chronic rhinosinusitis may be underestimated.

PMID- 29649893
TI  - A Three-Year Course of House Dust Mite Sublingual Immunotherapy Appears Effective
      in Controlling the Symptoms of Allergic Rhinitis.
AB  - Background Allergic rhinitis is the most common allergic disorder. Although the
      management of the disease is successful in many patients, based on guidelines,
      some of them remain with symptoms uncontrolled with pharmacotherapy. Presently,
      there is no substantiated information on the control of allergic rhinitis in
      patients who underwent sublingual immunotherapy. Objective The purpose of this
      prospective follow-up study was to assess the control of allergic rhinitis in
      adults after a three-year course of house dust mite sublingual immunotherapy.
      Methods This prospective real-life study was designed to include adults with
      moderate to severe allergic rhinitis sensitized to house dust mite who underwent
      a three-year course of sublingual immunotherapy. Control of symptoms was assessed
      by Rhinitis Control Assessment Test (RCAT) after three years of house dust mite
      sublingual immunotherapy. Additionally, patients assessed their symptoms by
      utilizing a visual analog scale. Results A total number of 86 consecutively
      enrolled patients (46 (53.49%) men; mean age 26.10 years (SD = 5.85)) with
      moderate to severe allergic rhinitis and clinically relevant sensitization to
      house dust mite were evaluated. When assessed by RCAT on the third year, 74
      (86.05%) had well-controlled symptoms and 20 (27.03%) of them were completely
      controlled. A significant reduction in visual analog scale scores-from 7.52 cm at
      baseline to 2.31 cm-was established ( P < 0.0001). There was a strong negative
      correlation between RCAT scores and visual analog scale (r = -0.65; P < 0.01).
      Conclusion This study provided evidence that a three-year course of house dust
      mite sublingual immunotherapy appears effective in controlling the symptoms of
      allergic rhinitis.

PMID- 29649894
TI  - Use of Neural Response Telemetry for Pediatric Cochlear Implants: Current
      Practice.
AB  - OBJECTIVES: Evaluate usage trends of neural response telemetry (NRT) in cochlear
      implant centers across the nation and assess reported benefits of intraoperative
      NRT for pediatric cochlear implant recipients. STUDY DESIGN: Survey. STUDY
      PARTICIPANTS: All US cochlear implant centers (n = 110). METHODS: A 15-question
      multiple-choice survey was distributed electronically to all centers. The survey
      captured demographic information of all centers, practice patterns surrounding
      the use of NRT, and the extent to which intraoperative NRT is of benefit.
      RESULTS: Thirty-two invited participants (29%) completed the survey. A majority
      of participants reported practicing in an academic center (66%), followed by a
      hospital setting (19%) and private practice (16%). Seventy-two percent of survey
      participants reported using NRT for pediatric cochlear implant recipients. Sixty
      three percent felt it improved the ability to program at initial activation, and
      50% of participants felt that NRT improves satisfaction at initial activation.
      CONCLUSION: This study suggests that a majority of surgeons use intraoperative
      NRT for pediatric cochlear implantation as an additional measure to ensure
      appropriate electrode placement and improve device activation. Larger studies are
      needed to better establish the relationship between intraoperative NRT and
      postoperative outcomes and justify the additional costs associated with
      intraoperative NRT.

PMID- 29649895
TI  - The Impact of Overweight/Obesity Duration and Physical Activity on Medical
      Multimorbidity: Examining the WATCH Paradigm.
AB  - PURPOSE:: The "fat-but-fit" paradigm has been evaluated. However, the duration of
      overweight/obesity within the "fat-but-fit" paradigm (ie, assessing body mass at
      more than 1 time point) has not been extensively evaluated, which was this
      study's purpose. DESIGN:: Cross-sectional. SETTING:: National Health and
      Nutrition Examination Survey 2003 to 2006. PARTICIPANTS:: Ages 36 to 85; N =
      3621. MEASURES:: Physical activity assessed via accelerometry. Medical
      multimorbidity was assessed via physician diagnosis of 13 chronic diseases.
      Height and body mass were directly measured for current body mass index (BMI),
      and 10-year prior BMI was calculated using current height and self-reported
      weight 10 years prior. Six mutually exclusive groups were created: (1) active,
      normal weight now and 10 years ago; (2) inactive, normal weight now and 10 years
      ago; (3) active, overweight/obese now but not 10 years ago; (4) active,
      overweight/obese now and 10 years ago; (5) inactive, overweight/obese now but not
      10 years ago; and (6) inactive, overweight/obese now and 10 years ago. ANALYSIS::
      Logistic regression. RESULTS:: Compared to group 1, adjusted odds ratios (ORs)
      were as follows: group 2: OR = 2.0 ( P = .004), group 3: OR = 1.7 ( P = .004),
      group 4: OR = 2.5 ( P < .001), group 5: OR = 2.9 ( P < .001), and group 6: OR =
      4.8 ( P < .001). CONCLUSIONS:: All patterns of weight change/duration and
      activity level altered the odds of medical multimorbidity, suggesting that the
      duration of overweight/obesity should also be taken into consideration when
      assessing the "fat-but-fit" paradigm.

PMID- 29649896
TI  - The Role of Managers in Employee Wellness Programs: A Mixed-Methods Study.
AB  - PURPOSE:: The purpose of this study is to evaluate managers' barriers and
      facilitators to supporting employee participation in the Washington State
      Wellness program. DESIGN:: Exploratory sequential mixed methods. SETTING:: Four
      Washington State agencies located in Olympia and Tumwater, Washington.
      PARTICIPANTS:: State employees in management positions (executive, middle, and
      line), whose job includes supervision of subordinates and responsibility for the
      performance and conduct of a subunit or group. METHODS:: We interviewed 23
      managers and then used the results to create a survey that was fielded to all
      managers at the 4 agencies. The survey response rate was 65% (n = 607/935).
      ANALYSIS:: We used qualitative coding techniques to analyze interview transcripts
      and descriptive statistics to summarize survey data. We used the Total Worker
      Health framework to organize our findings and conclusions. RESULTS:: Managers
      support the wellness program, but they also face challenges with accommodating
      employees' participation due to workload, scheduling inflexibility, and self
      efficacy to discuss wellness with direct reports. About half the managers receive
      support from the manager above them, and most have not received training on the
      wellness program. CONCLUSION:: Our findings point to several strategies that can
      strengthen managers' role in supporting the wellness program: the provision of
      training, targeted messages, formal expectations, and encouragement (from the
      manager above) to support employees' participation.

PMID- 29649897
TI  - An Investigation of Youth Assets and Physical Activity and BMI Using a
      Longitudinal Cohort Design.
AB  - PURPOSE:: Substantial research has demonstrated that assets (eg, family
      communication, school connectedness) protect youth from participation in numerous
      risk behaviors. However, very few studies have explored the relationship between
      assets and positive health behaviors. This study investigated prospective
      associations among assets and physical activity (PA) and body mass index (BMI).
      DESIGN:: Longitudinal design with 5 waves of data collected annually over a 4
      year period. SETTING:: Community-based setting with participants recruited via
      door-to-door canvasing of homes located in stratified (by race and income)
      randomly selected census tracts and blocks. PARTICIPANTS:: Participants were 1111
      youth (baseline mean age = 14.3 years [SD = 1.6]; 53% female; 40.6% white, 28.6%
      Hispanic, 24.4% black, 6.4% other) and their parents. MEASURES:: Weekly
      participation in PA, BMI, and 14 youth assets representing multiple levels of
      influence (individual, family, and community). ANALYSIS:: Generalized linear
      mixed models assessed associations among the assets and PA and BMI over the 5
      waves of data. RESULTS:: There was a significant and graded relationship between
      assets and weekly participation in PA. For example, at the community-asset level,
      PA minutes were higher among youth with 2 assets ( P = .006), 3 assets ( P =
      .0006), and 4 to 5 assets ( P < .0001) compared to youth with 0 to 1 assets. No
      effects were found for BMI. CONCLUSION:: Asset-based health promotion programs
      for youth may promote positive health behaviors and prevent participation in risk
      behaviors.

PMID- 29649899
TI  - Managers' Support for Employee Wellness Programs: An Integrative Review.
AB  - OBJECTIVE:: The aim of this integrative literature review is to synthesize the
      existing evidence regarding managers' support for employee wellness programs.
      DATA SOURCE:: The search utilized multiple electronic databases and libraries.
      STUDY INCLUSION AND EXCLUSION CRITERIA:: Inclusion criteria comprised peer
      reviewed research published in English, between 1990 and 2016, and examining
      managers' support in the context of a worksite intervention. The final sample
      included 21 articles for analysis. DATA EXTRACTION:: Two researchers extracted
      and described results from each of the included articles using a content
      analysis. DATA SYNTHESIS:: Two researchers independently rated the quality of the
      included articles. Researchers synthesized data into a summary table by study
      design, sample, data collected, key findings, and quality rating. RESULTS::
      Factors that may influence managers' support include their organization's
      management structure, senior leadership support, their expected roles, training
      on health topics, and their beliefs and attitudes toward wellness programs and
      employee health. Managers' support may influence the organizational culture,
      employees' perception of support, and employees' behaviors. CONCLUSIONS:: When
      designing interventions, health promotion practitioners and researchers should
      consider strategies that target senior, middle, and line managers' support.
      Interventions need to include explicit measures of managers' support as part of
      the evaluation plan.

PMID- 29649898
TI  - The Minne-Loppet Motivation Study: An Intervention to Increase Motivation for
      Outdoor Winter Physical Activity in Ethnically and Racially Diverse Elementary
      Schools.
AB  - PURPOSE:: To test the effectiveness of an intervention to increase motivation for
      physical activity in racially diverse third- through fifth-grade students.
      DESIGN:: Natural experiment. SETTING:: Elementary schools in Minneapolis,
      Minnesota. PARTICIPANTS:: Two hundred ninety-one students in 18 Minne-Loppet Ski
      Program classes and 210 students in 12 control classrooms from the same schools.
      INTERVENTION:: The Minne-Loppet Ski Program, an 8-week curriculum in elementary
      schools that teaches healthy physical activity behaviors through cross-country
      skiing. MEASURES:: Pretest and posttest surveys measured self-determination
      theory outcomes: intrinsic exercise motivation, intrinsic ski motivation,
      autonomy, competence, and relatedness. ANALYSIS:: Hierarchical linear regression
      models tested treatment effects controlled for grade, race, sex, and baseline
      measures of the outcomes. RESULTS:: Minne-Loppet program students showed
      significantly greater motivation to ski (beta = 0.95, 95% confidence interval
      [CI]: 0.15-1.75) and significantly greater perceived competence (beta = 0.78, 95%
      CI: 0.06-1.50) than students in control classrooms. Treatment effects for general
      exercise motivation and perceived competence differed by race. African American
      students in Minne-Loppet classes showed significantly greater general exercise
      motivation (beta = 1.08, 95% CI: 0.03-2.14) and perceived competence (beta =
      1.95, 95% CI: 0.91-2.99) than African American students in control classes.
      CONCLUSION:: The Minne-Loppet program promoted perceived competence and
      motivation to ski. Future improvements to the Minne-Loppet and similar
      interventions should aim to build general motivation and provide support needed
      to better engage all participants.

PMID- 29649900
TI  - In Vitro Comparison of a Novel Single Probe Dual-Energy Lithotripter to Current
      Devices.
AB  - PURPOSE: The LithoClast Trilogy is a novel single probe, dual-energy lithotripter
      with ultrasonic (US) vibration and electromagnetic impact forces. ShockPulse and
      LithoClast Select are existing lithotripters that also use a combination of US
      and mechanical impact energies. We compared the efficacy and tip motion of these
      devices in an in vitro setting. MATERIALS AND METHODS: Begostones, in the ratio
      15:3, were used in all trials. Test groups were Trilogy, ShockPulse, Select
      ultrasound (US) only, and Select ultrasound with pneumatic (USP). For clearance
      testing, a single investigator facile with each lithotripter fragmented 10 stones
      per device. For drill testing, a hands-free apparatus with a submerged balance
      was used to apply 1 or 2 lbs of pressure on a stone in contact with the device
      tip. High-speed photography was used to assess Trilogy and ShockPulse's probe tip
      motion. RESULTS: Select-USP was slowest and Trilogy fastest on clearance testing
      (p < 0.01). On 1 lbs drill testing, Select-US was slowest (p = 0.001). At 2 lbs,
      ShockPulse was faster than Select US (p = 0.027), but did not significantly
      outpace Trilogy nor Select-USP. At either weight, there was no significant
      difference between Trilogy and ShockPulse. During its US function, Trilogy's
      maximum downward tip displacement was 0.041 mm relative to 0.0025 mm with
      ShockPulse. Trilogy had 0.25 mm of maximum downward displacement during its
      impactor function while ShockPulse had 0.01 mm. CONCLUSIONS: Single probe dual
      energy devices, such as Trilogy and ShockPulse, represent the next generation of
      lithotripters. Trilogy more efficiently cleared stone than currently available
      devices, which could be explained by its larger probe diameter and greater
      downward tip displacement during both US and impactor functions.

PMID- 29649901
TI  - Kidney Stone Composition in Third-World Areas: What Kashgar Tells Us?
AB  - OBJECTIVE: To analyze urinary stone compositions in patients from Kashgar, China.
      MATERIALS AND METHODS: We analyzed the components of urinary stones in 732
      consecutive patients with urolithiasis admitted to the First and Second People's
      Hospital of Kashgar Prefecture, Xinjiang, from July 2014 to November 2016. The
      patients were divided into two groups by ages: group A, 0 to 18 years and group
      B, >18 years old. The distributions of various stone compositions were analyzed
      and correlated with the gender and age. RESULTS: The mean age of group A was 3.90
      +/- 4.09 years and that of group B was 39.88 +/- 16.40 years. The overall gender
      ratio (male:female) was 2.27:1. Ammonium acid urate (AAU) stone was the most
      frequent stone, male 35.83% and female 33.48%. Female patients were significantly
      more common than male patients in calcium apatite stone (p = 0.004). Of all 732
      cases, patients younger than 18 years were more than patients older than 18 years
      (58.47% vs 41.53%). The majority of the patients (77.87%) had the stone located
      in the upper urinary tract. Two peak ages for both genders were noted in 1 to 3
      years and 19 to 40 years group of the patients. In group of 1 to 3 years
      patients, male were more than female (37.60% vs 24.55%, p = 0.001), whereas in
      the group of 10 to 18 years patients, female were more than male (10.71% vs
      4.13%). AAU was the predominant stone component in group <1 year (70. 5%, p <
      0.01, as compared with other groups.). Uric acid stone was more prevalent in
      group >60 years (66.8%, p < 0.01) than in other groups. Patients in 1 to 3 years
      were in the peak age group of AAU stones in both the upper and lower urinary
      tract. CONCLUSION: Most of the patients with urolithiasis diagnosed and treated
      in Kashgar are <18 years old, especially younger than 3 years old. The most
      frequent stone component in this area was AAU. More than 50% patients <18 years
      old had AAU stone. The mechanisms that could trigger the high prevalence of AAU
      stone in patients <18 years old are worth further investigation.

PMID- 29649902
TI  - Fetal MR imaging in urogenital system anomalies.
AB  - Fetal magnetic resonance imaging (MRI) is an important adjunct to ultrasound in
      evaluation of fetal urogenital system. While, ultrasound remains the primary
      modality, MRI helps in more complicated cases or where ultrasound is limited due
      to technical factors such as poor acoustic window. The goal of this article is to
      review the common fetal urogenital anomalies and their imaging manifestations on
      ultrasound and MRI, and discuss how MRI adds diagnostic value.

PMID- 29649904
TI  - Economic burden of treatment failure in chronic lymphocytic leukemia patients.
AB  - OBJECTIVE: This study assessed healthcare costs of first-line treatment failure
      (TF) in patients with chronic lymphocytic leukemia (CLL), a subtype of non
      Hodgkin's lymphoma. METHODS: Pre-diagnosis treatment-naive adults with >=2 CLL
      diagnoses initiated on an antineoplastic agent (index date) after their first CLL
      diagnosis with >=12 and >=6 months of continuous observation pre- and post-index,
      respectively, were selected from the Truven Health MarketScan Research Databases.
      Patients had no solid malignancies in the pre-index period nor selected blood
      malignancies at any time. Initial therapy included antineoplastic agents
      initiated in the first 30 days post-index. TF occurred at the earliest of:
      initiation of a new antineoplastic agent, treatment resumption following a >=3
      month break, non-chemotherapy intervention (stem cell transplant or
      radiotherapy), hospice care or hospital mortality. The cost of TF was evaluated
      as the healthcare cost difference between patients with and without first-line TF
      using ordinary least square regressions adjusted for baseline characteristics.
      Non-parametric bootstrap was used to evaluate statistical significance. RESULTS:
      Among 2226 patients identified (mean age: 68 years; female: 41%), 46% experienced
      first-line TF. The average TF cost was $3011 per patient per month (p < .001).
      When stratifying patients by event indicating TF and by most common therapies,
      non-chemotherapy intervention ($7582 per patient per month; p < .0001) and
      fludarabine/cyclophosphamide/rituximab ($4758; p < .001) were associated with the
      highest TF cost, respectively. CONCLUSIONS: The cost of first-line TF is high and
      varies across first-line therapies. This should be considered when selecting the
      initial therapy in these patients.

PMID- 29649903
TI  - Pharmacokinetic evaluation of quetiapine fumarate controlled release hybrid
      hydrogel: a healthier treatment of schizophrenia.
AB  - The current study aimed to rationally develop and characterize pH-sensitive
      controlled release hydrogels by graft polymerization of gelatin (Gel) and
      hydroxypropyl methyl cellulose (HPMC) in the presence of glutaraldehyde (GA)
      using quetiapine fumarate for the treatment of schizophrenia. The prepared
      hydrogels discs were subjected to various physicochemical studies including:
      swelling, diffusion, porosity, sol-gel analysis, Fourier transform infrared
      spectroscopy, differential scanning calorimetry, and scanning electron
      microscopy. Three different pH values (1.2, 6.8 and 7.4) were used to determine
      shape, transition, and controlled release behavior of prepared hydrogels. Various
      kinetic models including zero order, first order, Higuchi model and Power Law
      equation were applied on drug release data. The optimized hydrogels were
      subjected to in vivo studies using albino rabbits. Swelling and release results
      were found to be insignificant (p < .05) evidencing that there was no significant
      difference in swelling and drug release rate of hydrogels in different pH
      mediums. Swelling, porosity, gel-fraction, and drug released (%) were found to be
      dependent on concentrations of Gel, HPMC, and GA. Kinetic models revealed that
      QTP-F release followed non-Fickian diffusion. In-vivo studies contributed
      significantly higher plasma QTP-F concentration (Cmax), time for maximum plasma
      concentration (Tmax), area under the curve (AUC0-inf) and half-life (t1/2) as
      18.32 +/- 0.50 ug/ml, 8.00 +/- 0.01 hrs, 6021.2 +/- 5.09 ug.hrs/ml and 10.06 +/-
      0.43 hrs, respectively, for test-hydrogels when compared to reference market
      brand (Qusel(r) 200 mg, Hilton Pharma, Karachi, Pakistan) QTP-F tablets. It might
      be concluded that QTP-F loaded pH-sensitive hydrogels were developed successfully
      with reduced dosing frequency for schizophrenia.

PMID- 29649905
TI  - The Effect of Acupressure on Pain in Cancer Patients With Bone Metastasis: A
      Nonrandomized Controlled Trial.
AB  - BACKGROUND: Pain is a serious and common problem in bone metastases. For this
      purpose, complementary and supportive practices are also applied along with
      medical treatment. This study was conducted for the purpose of evaluating the
      effect of acupressure on pain in cancer patients with bone metastasis. METHODS:
      The study was conducted in a nonrandomized controlled trial with patients who
      applied to the radiotherapy unit of an oncology hospital. The data of the study
      were collected by using a questionnaire and the Visual Analog Scale. A total of 8
      acupressure sessions, which lasted for approximately 10 minutes each (with
      warming and acupressure periods), was applied to the intervention group. The data
      were analyzed by using chi2 test, paired t test, and Pearson's correlation
      coefficient. RESULTS: It was determined that the pain mean score of the
      intervention group was 7.6 +/- 1.9 before the acupressure and decreased to 6.8 +/
      1.9 after the acupressure and this result was statistically significant. On the
      other hand, no significant difference was determined in the pain mean score of
      the control group. CONCLUSIONS: Acupressure is applicable for cancer patients
      with bone metastasis by nursing staff after receiving brief training and may make
      a difference in relieving pain of the patients. Further well-designed trials
      should be conducted.

PMID- 29649906
TI  - Knockdown of LncRNA MALAT1 contributes to the suppression of inflammatory
      responses by up-regulating miR-146a in LPS-induced acute lung injury.
AB  - BACKGROUND: Acute lung injury (ALI) is a type of severe pulmonary inflammatory
      disease with high rates of morbidity and mortality. Now, an increasing number of
      studies suggest that lncRNAs may act as key regulators of the inflammatory
      response and play a crucial role in the pathogenesis of many inflammatory
      diseases. Our study firstly explored the function and underlying mechanism of
      lncRNA metastasis-associated lung adenocarcinoma transcription 1 (MALAT1) in
      regulating the inflammatory response of lipopolysaccharide (LPS)-induced ALI in
      rats. METHODS: The ALI rats were constructed by intratracheal instillation with
      LPS. Hematoxylin and eosin (HE) for histological examination were performed to
      detect histopathological changes in the lung tissues. Enzyme-linked immunosorbent
      assay (ELISA) was used to determine the concentrations of cytokines TNF-alpha, IL
      6, and IL-1beta in the supernatants of the bronchoalveolar lavage fluid (BALF).
      Quantitative real-time PCR (qRT-PCR) analysis was employed to assess the
      expression of MALAT1, miR-146a, TNF-alpha, IL-6, and IL-1beta in lung tissues.
      Luciferase reporter assay and RNA immunoprecipitation (RIP) assay were used to
      detect the relationship between MALAT1 and miR-146a. RESULTS: The results
      revealed that MALAT1 knockdown played a protective role in the LPS-induced ALI
      rat model. In addition, knockdown of MALAT1 in vitro inhibited LPS-induced
      inflammatory response in murine alveolar macrophages cell line MH-S and murine
      alveolar epithelial cell line MLE-12. This study found that MALAT1 acts as a
      molecular sponge for miR-146a and MALAT1 negatively regulated miR-146a
      expression. Mechanistically, MALAT1 overexpression alleviated the inhibitory
      effect of miR-146a on LPS-induced inflammatory response in MH-S. CONCLUSIONS:
      Together, our study provided the first evidence that MALAT1 knockdown could
      suppress inflammatory response by up-regulating miR-146a in LPS-induced ALI,
      which provided a potential therapeutic target for the treatment of ALI.

PMID- 29649907
TI  - Farnesoid X receptor modulators 2014-present: a patent review.
AB  - INTRODUCTION: The nuclear receptor FXR regulates the expression of genes involved
      in bile acids, glucose and lipid homeostasis. For its role as guardian of
      metabolism, FXR has been identified a promising pharmacological target in liver
      bile acid and lipid accumulation, such as cholestasis and non-alcoholic fatty
      liver disease (NAFLD). The field of FXR research is extremely competitive with a
      large number of patents and articles published in the last decades identifying
      promising hit compounds. Areas covered. The present review summarizes recent
      patent activity (2014-to date) filing for synthetic and natural FXR ligands,
      including bile acid derivatives and non-steroidal compounds, alongside their in
      vitro and in vivo efficacy as well as their therapeutic applications. Expert
      opinion. While the first FXR agonist, obeticholic acid, has gained approval,
      significant safety issues have been emerged. Today is unclear whether these
      safety issues are class related or restricted to the bile acid scaffold of this
      agent. Despite the significant number of patent applications claiming steroidal
      and non-steroidal FXR agonists, several questions on their therapeutic potential
      in cholestasis and NASH remain open leaving a space for the development of novel
      compounds.

PMID- 29649908
TI  - Invisible realities: Caring for older Moroccan migrants with dementia in Belgium.
AB  - The number of older Moroccan migrants reaching the age of high risk for dementia
      is increasing in Belgium. Yet no study has been performed to explore how Moroccan
      families facing dementia experience and manage the condition. The study employed
      a qualitative design using semi-structured interviews with 12 informal and 13
      formal caregivers to answer this research question. Findings indicate that the
      experience of dementia includes several invisible realities that challenge the
      informal and formal caregivers: (1) the invisibility of dementia as a condition;
      (2) the invisible subtleties of the informal care execution; (3) the invisibility
      and inaccessibility of care services as explanation for these family's non-use of
      available services; and (4) the overlooking of culture, migration and religion as
      invisible influencers of the overall dementia experience. A better understanding
      of these hidden realities of migrant older people with dementia and their
      caregivers could lead to interventions to provide effective and tailored person
      centred care that is sensitive to the individual's life experiences, culture and
      religious background.

PMID- 29649909
TI  - "Music & Memory" and improved swallowing in advanced dementia.
AB  - : Background Dysphagia and difficulty with eating affects a significant portion
      of individuals with advanced dementia. Such problems with oral intake can have
      serious health consequences including mealtime distress, dehydration and
      malnutrition, aspiration, reduced quality of life, and increased mortality risk.
      Design We present the first data indicating that "Music & Memory" interventions
      improve swallowing in individuals with advanced dementia, thereby making oral
      feeding easier and potentially diminishing reliance on PEG. Setting Columbia
      Health Care Center, Wyocena, WI (with Music&Memory.org, Mineola, NY and Stony
      Brook University). Participants Residents with advanced dementia (N = 5).
      MEASUREMENTS: Observation by eight professional caregivers. Results (1) Enhanced
      swallowing mechanism with Music & Memory prior to dining; (2) decreased incidents
      of choking during mealtime; (3) improved nutritional status; (4) reduced weight
      loss; (5) reduced need for speech interventions; (6) enhanced quality of life.
      Conclusions The preliminary results call for additional research.

PMID- 29649910
TI  - Variations in corticomotor excitability in response to distal focal thermal
      stimulation.
AB  - PURPOSE: This study investigated the effects of thermal stimulation on
      corticomotor excitability with transcranial magnetic stimulation (TMS). MATERIAL
      AND METHODS: Participants consisted of healthy young adults (n = 20) and seniors
      (n = 15). Each experimental session consisted of a baseline (BL) assessment,
      followed by a warming and a cooling protocol. At BL, recordings of motor evoked
      potentials (MEPs) and skin temperature were performed with the index finger
      covered with a 'neutral' gel pack (24  degrees C). For warming, the same
      measurements were performed, but with the index covered with a warmed gel pack
      (45  degrees C). The gel pack was kept for 5 min, and the measurements were
      performed at 1 min during warming and 5 and 10 min post. After a break,
      participants were tested with the cooling protocol (gel pack 10  degrees C) by
      repeating the same sequence as in the warming. RESULTS: The two thermal protocols
      induced the desired range of skin temperatures (warming = 35-45 degrees ; cooling
      = 13-24 degrees ). For MEP modulation, the primary analysis revealed no main
      effects or interactions, owing to the variability of responses to either warming
      or cooling stimulation. Further analysis of individual responses revealed that
      modulation, when present, was short-lasting and was characterized by a depression
      in about half of the participants. Facilitation was also observed, but only in
      smaller clusters, especially with cooling (13/35). Modulation in MEP amplitude
      did not correlate with changes in skin temperature. CONCLUSION: These results are
      consistent with previous reports regarding variability in response to sensory
      stimulation protocols. In the case of thermal stimulation, such variability
      likely reflects individual differences in the influences exerted by thermal
      afferents centrally.

PMID- 29649911
TI  - Curriculum development: A dynamic change inside the chrysalis.

PMID- 29649912
TI  - Post-combat adaptation: improving social support and reaching constructive
      growth.
AB  - BACKGROUND AND OBJECTIVES: Posttraumatic stress disorder, a commonly researched
      mental health outcome associated with trauma, does not develop in the majority of
      survivors. More common trajectories of adaptation include resilience, and
      posttraumatic growth (PTG). The objectives of the current study were to: (1)
      describe posttrauma adaptation profiles in a sample of Israeli male military
      veterans (N = 448); and (2) to explore the protective factors that promote
      constructive PTG within two profiles of posttrauma adaptation. METHODS: The study
      used secondary data to estimate latent profile mixture models and a series of
      logistic regression analyses. RESULTS: Demographic controls, combat related
      variables, endorsement of coping strategies, and reports of improvement in social
      support were not significant predictors of constructive growth in the resilient
      class. However, those in the struggling growth subset of the sample who reported
      improvement in perceived social support increased the odds of reaching
      constructive growth. CONCLUSION: These findings highlight the importance of
      tailored clinical interventions that account for more complex profiles of
      posttrauma adaptation; and further, provide evidence that adaptation takes place
      over time. Finally, these findings call for future research to continue to
      explore the quality of PTG and the contexts in which protective factors promote
      positive adaptation.

PMID- 29649913
TI  - Effects of an Exercise Intervention on Cancer-Related Fatigue and Its
      Relationship to Markers of Oxidative Stress.
AB  - BACKGROUND: Although the underlying mechanisms of cancer-related fatigue (CRF)
      are not fully characterized, treatment-associated oxidative stress may play a
      role. The purpose of this study was to determine the effect of an exercise
      intervention on the relationship between CRF and oxidative stress. METHODS: Upon
      cessation of radiation or chemotherapy, 8 cancer patients participated in a 10
      week exercise intervention (EX), while 7 continued standard care (CON). Blood
      draws and fatigue questionnaires were administered to cancer patients before and
      after the intervention as well as to 7 age-matched individuals with no cancer
      history. Changes in plasma 8-hydroxy-deoxyguanosine (8-OHdG), protein carbonyls,
      antioxidant capacity, and fatigue were compared between groups. Correlations
      between CRF and oxidative stress were evaluated. RESULTS: Mean total fatigue
      scores decreased significantly (5.0 +/- 2.2 to 2.6 +/- 1.5, P < .05) in EX, but
      not in CON. Antioxidant capacity significantly increased (+41%; P < .05) and
      protein carbonyls significantly decreased (-36%; P < .05) in EX, but not in CON.
      Increases in antioxidant capacity were significantly correlated with reductions
      in affective ( r = -.49), sensory ( r = -.47), and cognitive fatigue ( r = -.58).
      Changes in total ( r = .46) and affective ( r = .47) fatigue exhibited
      significant correlations with changes in 8-OHdG over time, while behavioral ( r =
      .46) and sensory ( r = .47) fatigue changes were significantly correlated with
      protein carbonyls. CONCLUSIONS: Oxidative stress may be implicated in CRF, while
      improved antioxidant capacity following an exercise intervention may play a role
      in mitigating CRF in cancer survivors.

PMID- 29649915
TI  - Filifactor alocis manipulates human neutrophils affecting their ability to
      release neutrophil extracellular traps induced by PMA.
AB  - Neutrophils operate at the site of injury or inflammation in the periodontal
      pocket to ensure periodontal health and clearance of bacterial pathogens.
      Filifactor alocis is recently identified as a potential periodontal pathogen, and
      in this study, we assessed the formation of neutrophil extracellular traps
      (NETs), in response to the presence of the organism . NET formation by human
      neutrophils was not induced when challenged with F. alocis, independent of
      opsonization, viability, time, or bacterial dose. F. alocis also failed to induce
      NETs from TNF-alpha-primed neutrophils and did not induce the release of
      extracellular neutrophil elastase. However, significant NET induction was
      observed when neutrophils were challenged with Streptococcus gordonii or
      Peptoanaerobacter stomatis, In addition, co-infection studies revealed that the
      presence of F. alocis with S. gordonii or P. stomatis does not enhance or reduce
      NETs. Additionally, F. alocis failed to impact pre-formed NETs induced by either
      S. gordonii or P. stomatis. Pretreatment with F. alocis prior to stimulation with
      phorbol 12-myristate 13-acetate (PMA), S. gordonii, or P. stomatis revealed that
      the bacterium is capable of reducing only PMA but not S. gordonii or P. stomatis
      NET formation. These results indicate that F. alocis manipulates neutrophils,
      inhibiting the triggering of NET induction.

PMID- 29649914
TI  - Positive affect skills may improve pain management in people with HIV.
AB  - Non-opioid pain management strategies are critically needed for people with HIV.
      We therefore conducted a secondary analysis of pain-related outcomes in a
      randomized controlled trial of a positive affect skills intervention for adults
      newly diagnosed with HIV ( N = 159). Results suggest that, even if pain
      prevalence rises, positive affect skills may reduce pain interference and prevent
      increased use of opioid analgesics by people living with HIV. Future research
      should replicate and extend these findings by conducting trials that are
      specifically designed to target pain outcomes.

PMID- 29649916
TI  - Patient perception of Breezhaler(r) and Ellipta(r) device feedback mechanisms in
      COPD: The ADVANTAGE Study.
AB  - OBJECTIVES: The primary objective of the ADVANTAGE study was to compare device
      naive chronic obstructive pulmonary disease (COPD) patients' perception of the
      Breezhaler(r) and Ellipta(r) devices' feedback mechanisms of dose delivery
      confirmation. The secondary objective was to assess comfort with the inhalers'
      mouthpiece in terms of ease to form a tight seal around the mouthpiece. These
      objectives were achieved by using a novel, patient perception of inhaler
      questionnaire developed and tested during cognitive interviews of patients by
      Evidera, London, United Kingdom. METHODS: Ten COPD patients were interviewed to
      collect feedback on the interpretation, relevance and language of the
      questionnaire. This questionnaire was then used in ADVANTAGE to compare patients'
      perception (n = 100) of both devices. Patients completed the questionnaire after
      a single inhalation of placebo through each inhaler. RESULTS: Using the final
      questionnaire, patients reported being more confident of the feedback mechanism
      of Breezhaler than that of the Ellipta device (mean score 4.3 versus 3.6
      respectively, estimated difference [95% CI]: 0.75 [0.51, 0.99], p < .0001).
      Patients also reported better comfort (ease to form a tight seal with the lips)
      with the Breezhaler mouthpiece than the Ellipta mouthpiece (mean score 4.3 versus
      3.9 respectively, estimated difference [95% CI]: 0.41 [0.21, 0.61], p < .0001).
      There were no safety concerns associated with either device. CONCLUSION: COPD
      patients showed greater preference for the Breezhaler over the Ellipta inhaler
      for confidence of dose delivery and comfort of the mouthpiece. TRIAL
      REGISTRATION: The trial is registered at ClinicalTrials.gov (ClinicalTrials.gov
      number NCT02551224).

PMID- 29649917
TI  - Association of obesity with healthcare resource utilization and costs in a
      commercial population.
AB  - OBJECTIVE: To examine the association of obesity with healthcare resource
      utilization (HRU) and costs among commercially insured individuals. METHODS: This
      retrospective observational cohort study used administrative claims from 1
      January 2007 to 1 December 2013. The ICD-9-CM status codes (V85 hierarchy) from
      2008 to 2012 classified body mass index (BMI) into the World Health
      Organizations' BMI categories. The date of first observed BMI code was defined as
      the index date and continuous eligibility for one year pre- and post- index date
      was ensured. Post-index claims determined individuals' HRU and costs. Sampling
      weights developed using the entropy balance method and National Health and
      Nutrition Examination Survey data ensured representation of the US adult
      commercially insured population. Baseline characteristics were described across
      BMI classes and associations between BMI categories, and outcomes were examined
      using multivariable regression. RESULTS: The cohort included 9651 individuals
      with BMI V85 codes. After weighting, the BMI distribution was: normal (31.1%),
      overweight (33.4%), obese class I (22.0%), obese class II (8.1%) and obese class
      III (5.4%). Increasing BMI was associated with greater prevalence of
      cardiometabolic conditions, including hypertension, type 2 diabetes and metabolic
      syndrome. The use of antihypertensives, antihyperlipidemics, antidiabetics,
      analgesics and antidepressants rose with increasing BMI. Greater BMI level was
      associated with increased inpatient, emergency department and outpatient
      utilization, and higher total healthcare, medical and pharmacy costs.
      CONCLUSIONS: Increasing BMI was associated with higher prevalence of
      cardiometabolic conditions and higher HRU and costs. There is an urgent need to
      address the epidemic of obesity and its clinical and economic impacts.

PMID- 29649918
TI  - The impact of unicornuate uterus on perinatal outcomes after IVF/ICSI cycles: a
      matched retrospective cohort study.
AB  - OBJECTIVE: To evaluate the impact of unicornuate uterus on perinatal outcomes
      after in vitro fertilization and/or intracytoplasmic sperm injection (IVF/ICSI)
      cycles. METHODS: We performed a retrospective cohort study including 160 women
      with unicornuate uterus and 1:1 matched controls with normally shaped uterus.
      They received IVF/ICSI treatment during January 2009 and December 2011. The
      perinatal outcomes were followed up till December 2014. RESULTS: There were no
      significant differences in pregnancy rate, clinical pregnancy rate or live birth
      rate (53.6 versus 52.7, 41.4 versus 43.5, 33.8% versus 31.8%) between unicornuate
      uterus group and controls. Their biochemical pregnancy rate (22.8 versus 17.5%)
      and miscarriage rate (16.0 versus 18.8%) were similar. No significant differences
      were identified in preterm birth rate (18.3 versus 11.8%), birthweight (3.24 +/-
      0.60 versus 3.33 +/- 0.54 kg) or birth length (50.47 +/- 2.33 versus 50.06 +/-
      2.40 cm) among the singletons. However, lower gestational age (35.56 +/- 2.68
      versus 36.71 +/- 1.73, p = .019), higher preterm birth rate (55.0 versus 34.4%, p
      = .038), lower birthweight (2.33 +/- 0.58 versus 2.69 +/- 0.38 kg, p = .001),
      lower birth length (45.33 +/- 2.46 versus 48.88 +/- 2.06 cm, p = .000), as well
      as higher rate of very low birthweight (13.2% versus 0, p = .007) were found for
      the twins from unicornuate uterus group. CONCLUSIONS: The results indicated
      unimpaired pregnancy and perinatal outcomes for women with unicornuate uterus
      conceiving one fetus. However, close attention should be paid to twin pregnancy
      in unicornuate uterus owing to increased risks of prematurity and low
      birthweight. Selected single embryo transfer is recommended for women with
      unicornuate uterus undergoing IVF/ICSI cycles.

PMID- 29649919
TI  - Single-compartment models of retinal ganglion cells with different
      electrophysiologies.
AB  - There are more than 15 different types of retinal ganglion cells (RGCs) in the
      mammalian retina. To model responses of RGCs to electrical stimulation, we use
      single-compartment Hodgkin-Huxley-type models and run simulations in the Neuron
      environment. We use our recently published in vitro data of different
      morphological cell types to constrain the model, and study the effects of
      electrophysiology on the cell responses separately from the effects of
      morphology. We find simple models that can match the spike patterns of different
      types of RGCs. These models, with different input-output properties, may be used
      in a network to study retinal network dynamics and interactions.

PMID- 29649920
TI  - Corneal transplantation trends in France from 2004 to 2015: A 12-year review.
AB  - PURPOSE: The aim of this study was to report the 12-year longitudinal trends in
      indication and corneal transplantation techniques in France from 2004 to 2015.
      RESULTS: The records of all corneal transplantations performed from 2004 to 2015
      in France were retrospectively reviewed. The patient indications and types of
      transplant performed were analyzed. A total of 46,658 corneal transplantations
      were performed between 2004 and 2015, with 34,187 (73.3%) penetrating
      keratoplasty and 10,452 (22.4%) lamellar keratoplasty. The leading surgical
      indications were secondary endothelial failure (24.3%), keratoconus (18.8%),
      regraft (13.5%), and Fuchs endothelial corneal dystrophy (15.1%). Endothelial
      keratoplasty became the preferred technique for endothelial diseases and deep
      anterior lamellar keratoplasty the preferred technique for keratoconus,
      surpassing penetrating keratoplasty in 2013. CONCLUSION: Secondary endothelial
      failure is the top indication for performing a keratoplasty over the 12-year
      period. There was a shift from penetrating keratoplasty to endothelial
      keratoplasty performed for Fuchs endothelial corneal dystrophy and secondary
      endothelial failure, and to deep anterior lamellar keratoplasty, performed for
      keratoconus. This highlights an important shift in managing corneal diseases
      toward the application of selective and more conservative surgeries and changes
      in indications in corneal transplantation.

PMID- 29649921
TI  - Prostate Cancer Information Available in Health-Care Provider Offices: An
      Analysis of Content, Readability, and Cultural Sensitivity.
AB  - Prostate cancer (PrCA) is the most common cancer affecting men in the United
      States, and African American men have the highest incidence among men in the
      United States. Little is known about the PrCA-related educational materials being
      provided to patients in health-care settings. Content, readability, and cultural
      sensitivity of materials available in providers' practices in South Carolina were
      examined. A total of 44 educational materials about PrCA and associated sexual
      dysfunction was collected from 16 general and specialty practices. The content of
      the materials was coded, and cultural sensitivity was assessed using the Cultural
      Sensitivity Assessment Tool. Flesch Reading Ease, Flesch-Kincaid Grade Level, and
      the Simple Measure of Gobbledygook were used to assess readability. Communication
      with health-care providers (52.3%), side effects of PrCA treatment (40.9%),
      sexual dysfunction and its treatment (38.6%), and treatment options (34.1%) were
      frequently presented. All materials had acceptable cultural sensitivity scores;
      however, 2.3% and 15.9% of materials demonstrated unacceptable cultural
      sensitivity regarding format and visual messages, respectively. Readability of
      the materials varied. More than half of the materials were written above a high
      school reading level. PrCA-related materials available in health-care practices
      may not meet patients' needs regarding content, cultural sensitivity, and
      readability. A wide range of educational materials that address various aspects
      of PrCA, including treatment options and side effects, should be presented in
      plain language and be culturally sensitive.

PMID- 29649922
TI  - Perceptions of rural school mental health services: a focus group study.
AB  - The presence of emotional or behavioural disorders has an impact on academic
      achievement. Access to behavioural health services is a challenge, particularly
      in rural communities. School-based mental health services have been recognised as
      an effective means of addressing the needs of students with emotional or
      behavioural disorders. This qualitative focus group study explored the service
      needs, gaps, and barriers to mental health services. Themes related to time,
      space, family engagement, and education for teachers and caregivers emerged from
      the focus groups.

PMID- 29649923
TI  - Diffuse dermatophytosis occurring on dimethyl fumarate therapy.
AB  - BACKGROUND: Opportunistic infections have occurred during dimethyl fumarate (DMF)
      therapy. OBJECTIVE: Diffuse skin dermatophytosis which occurred during DMF
      therapy in the setting of lymphopenia is described. METHODS AND RESULTS: The
      clinical course, the lymphocyte subset profile, and dermatologic evaluations were
      reviewed. In both instances, there was no other cause of lymphopenia or immune
      suppression, and it is likely that the tinea infections are associated with DMF
      therapy. CONCLUSION: The occurrence of dermatophytosis widens the spectrum of
      opportunistic infections associated with DMF therapy. Further research is
      necessary to fully elucidate the mechanism of lymphopenia and potentially
      impaired immune competence during DMF therapy.

PMID- 29649924
TI  - Polarization of Microglia to the M2 Phenotype in a Peroxisome Proliferator
      Activated Receptor Gamma-Dependent Manner Attenuates Axonal Injury Induced by
      Traumatic Brain Injury in Mice.
AB  - Increasing evidence indicates that activated microglia play an important role in
      the inflammatory response following traumatic brain injury (TBI). Inhibiting M1
      and stimulating M2 activated microglia have demonstrated protective effects in
      several animal models of central nervous system diseases. However, it is not
      clear whether the polarization of microglia to M2 attenuates axonal injury
      following TBI. In this study, we used a lateral fluid percussion injury device to
      induce axonal injury in mice. Mice were randomly assigned to the sham, TBI, TBI +
      rosiglitazone (peroxisome proliferator-activated receptor gamma [PPAR-gamma]
      agonist), and TBI + GW9662 (PPAR-gamma antagonist) groups. Axonal injury was
      assessed using immunohistochemical staining for beta amyloid precursor protein.
      The inflammatory response was assessed by enzyme-linked immunosorbent assay,
      microglia polarization was assessed using specific markers of M1 and M2
      microglia, and neurological function was assessed using the neurological severity
      score. Following TBI, microglia of the M1 phenotype increased significantly,
      while those of the M2 phenotype decreased. Rosiglitazone-induced PPAR-gamma
      activation promoted microglia polarization to the M2 phenotype, which reduced the
      inflammatory response, attenuated axonal injury in the cerebral cortex, and
      improved neurological function. Conversely, GW9662 inhibited the polarization of
      microglia to M2 and aggravated inflammation and axonal injury. Our in vitro
      findings in lipopolysaccharide-induced microglia were consistent with those of
      our in vivo experiments. In conclusion, the polarization of microglia to the M2
      phenotype via PPAR-gamma activation attenuated axonal injury following TBI in
      mice, which may be a potential therapeutic approach for TBI-induced axonal
      injury.

PMID- 29649925
TI  - Validity and Reliability of the Turkish Version of the Adapted Rhodes Index of
      Nausea and Vomiting for Pediatrics by Child (ARINVc) and by Parent (ARINVp).
AB  - The study was conducted methodologically to adapt the Adapted Rhodes Index of
      Nausea and Vomiting for Pediatrics by Child (ARINVc) and Adapted Rhodes Index of
      Nausea and Vomiting for Pediatrics by Parent (ARINVp) into Turkish. The scales
      are administered to children who receive chemotherapy and to their parents,
      respectively. The study sample consisted of 8- to 18-year-old children who were
      hospitalized in the pediatric oncology and hematology clinics of a university
      hospital, met the sampling criteria, and agreed to participate in the research.
      The study data were collected with the Sociodemographic Attributes Information
      Form, ARINVc, and ARINVp using the face-to-face interview method. The mean ages
      of the children and their mothers and fathers who participated in the study were
      13.26 +/- 2.01, 36.33 +/- 5.10, and 40.17 +/- 4.94 years, respectively. The mean
      total scores obtained from the ARINVc and ARINVp were 5.43 +/- 4.06 and 5.70 +/-
      3.77, respectively. While Cronbach's alpha reliability coefficients of the scales
      were .85 for the ARINVc and .84 for the ARINVp, the item-total correlation
      coefficients were between 0.60 and 0.89 for the ARINVc and between 0.66 and 0.85
      for the ARINVp ( P < .01). The Turkish versions of ARINVc and ARINVp were
      determined to be valid and reliable scales.

PMID- 29649926
TI  - Social versus biological psychiatry: It's time for integration!

PMID- 29649927
TI  - Distinct episodic contexts enhance retrieval-based learning.
AB  - Spaced retrieval practice results in better long-term retention than massed
      retrieval practice. The episodic context account of this effect suggests that
      updated representations of the more distinct temporal contexts associated with
      spaced retrievals facilitate later recall. We examined whether environmental
      context, in addition to temporal context, may also play a role in retrieval-based
      learning. Participants studied and then attempted to retrieve the English
      translations of Swahili words during four acquisition blocks of trials. They were
      then randomly assigned to practice retrieving items three more times in one of
      the following conditions: massed practice with the same environmental context
      scene; massed practice with different environmental context scenes; spaced
      practice with the same environmental context scene; or spaced practice with
      different environmental context scenes. After a one-week delay, measures of
      recall, forgetting, and the joint probabilities between study session recall and
      final recall performance all indicated enhanced retention for both the spaced and
      different environmental context conditions. Indeed, after retrieving items in the
      study session, forgetting them during final recall was 371% more likely in the
      same context than in the different context conditions. These findings redefine
      and refine previous accounts of the episodic context model of retrieval-based
      learning.

PMID- 29649928
TI  - Non-Invasive Activation of Cervical Spinal Networks after Severe Paralysis.
AB  - Paralysis of the upper extremities following cervical spinal cord injury (SCI)
      significantly impairs one's ability to live independently. While regaining hand
      function or grasping ability is considered one of the most desired functions in
      tetraplegics, limited therapeutic development in this direction has been
      demonstrated to date in humans with a high severe cervical injury. The underlying
      hypothesis is that after severe cervical SCI, nonfunctional sensory-motor
      networks within the cervical spinal cord can be transcutaneously neuromodulated
      to physiological states that enable and amplify voluntary control of the hand.
      Improved voluntary hand function occurred within a single session in every
      subject tested. After eight sessions of non-invasive transcutaneous stimulation,
      combined with training over 4 weeks, maximum voluntary hand grip forces increased
      by ~325% (in the presence of stimulation) and ~225% (when grip strength was
      tested without simultaneous stimulation) in chronic cervical SCI subjects
      (American Spinal Injury Association Impairment Scale [AIS] B, n = 3; AIS C, n =
      5) 1-21 years post-injury). Maximum grip strength improved in both the left and
      right hands and the magnitude of increase was independent of hand dominance. We
      refer to the neuromodulatory method used as transcutaneous enabling motor control
      to emphasize that the stimulation parameters used are designed to avoid directly
      inducing muscular contractions, but to enable task performance according to the
      subject's voluntary intent. In some subjects, there were improvements in
      autonomic function, lower extremity motor function, and sensation below the level
      of the lesion. Although a neuromodulation-training effect was observed in every
      subject tested, further controlled and blinded studies are needed to determine
      the responsiveness of a larger and broader population of subjects varying in the
      type, severity, and years post-injury. It appears rather convincing, however,
      that a "central pattern generation" phenomenon as generally perceived in the
      lumbosacral networks in controlling stepping neuromodulator is not a critical
      element of spinal neuromodulation to regain function among spinal networks.

PMID- 29649930
TI  - Pulmonary paracoccidioidomycosis associated with the use of natalizumab in
      multiple sclerosis.
AB  - BACKGROUND: Natalizumab (NTZ) is a monoclonal antibody with an immunosuppressive
      effect that reduces the inflammation of the central nervous system, and it has
      been used for the treatment of relapsing-remitting multiple sclerosis (RRMS). In
      patients with low cellular immune response, systemic mycosis arising from endemic
      areas may occur. RESULTS AND CONCLUSION: In this article, we will describe a case
      of paracoccidioidomycosis as a complication to treatment with NTZ in an RRMS
      patient.

PMID- 29649929
TI  - A Real-Time Near-Infrared Fluorescence Imaging Method for the Detection of Oral
      Cancers in Mice Using an Indocyanine Green-Labeled Podoplanin Antibody.
AB  - Podoplanin is distinctively overexpressed in oral squamous cell carcinoma than
      oral benign neoplasms and plays a crucial role in the pathogenesis and metastasis
      of oral squamous cell carcinoma but its diagnostic application is quite limited.
      Here, we report a new near-infrared fluorescence imaging method using an
      indocyanine green (ICG)-labeled anti-podoplanin antibody and a desktop/a handheld
      ICG detection device for the visualization of oral squamous cell carcinoma
      xenografted tumors in nude mice. Both near-infrared imaging methods using a
      desktop (in vivo imaging system: IVIS) and a handheld device (photodynamic eye:
      PDE) successfully detected oral squamous cell carcinoma tumors in nude mice in a
      podoplanin expression-dependent manner with comparable sensitivity. Of these 2
      devices, only near-infrared imaging methods using a handheld device visualized
      oral squamous cell carcinoma xenografts in mice in real time. Furthermore, near
      infrared imaging methods using the handheld device (PDE) could detect smaller
      podoplanin-positive oral squamous cell carcinoma tumors than a non-near-infrared,
      autofluorescence-based imaging method. Based on these results, a near-infrared
      imaging method using an ICG-labeled anti-podoplanin antibody and a handheld
      detection device (PDE) allows the sensitive, semiquantitative, and real-time
      imaging of oral squamous cell carcinoma tumors and therefore represents a useful
      tool for the detection and subsequent monitoring of malignant oral neoplasms in
      both preclinical and some clinical settings.

PMID- 29649931
TI  - Self-Management in Liver Transplant Recipients: A Narrative Review.
AB  - INTRODUCTION: Although self-management is essential for liver transplant
      recipients, there is no review that has synthesized findings related to self
      management in this population. OBJECTIVE: This narrative review aimed to
      synthesize the current findings and identify the gaps in knowledge about self
      management in liver recipients. METHODS: A search of PubMed, CINAHL Plus,
      PsychINFO, ProQuest, and Web of Science was conducted using the following terms:
      [Self-care OR Self-management OR Health behavior] AND [Liver transplantation].
      Peer-reviewed published research articles focusing on self-management of adult
      recipients were selected. A total of 23 articles were included for review. Two
      reviewers independently reviewed the full text of selected articles and extracted
      the data about definitions, measurements, and findings regarding self-management.
      RESULTS: Three areas of self-management were identified, including medication
      nonadherence (n = 11), alcohol recidivism (n = 11), and health maintenance (n =
      5). Reported rates of medication nonadherence ranged from 8% to 66%. Medication
      nonadherence was related to recipients' demographic (eg, age or sex), transplant
      related (eg, time since transplant), and pretransplant variables (eg, history of
      substance/alcohol abuse). Reported alcohol recidivism rates ranged from 3% to
      95%. Age, pretransplant variables (eg, abstinent time before transplant), and
      personality disorder were identified to be related to alcohol recidivism after
      transplant. The health maintenance studies discussed behaviors such as smoking,
      clinic appointment attendance, or vaccination/health screening behaviors of
      recipients. DISCUSSION: Self-management studies in liver recipients have been
      narrowly focused on medication nonadherence and alcohol recidivism. To improve
      self-management in recipients, self-management beyond medication nonadherence and
      alcohol recidivism should be comprehensively examined.

PMID- 29649932
TI  - Optimal tube length of orotracheal intubation for mice.
AB  - Endotracheal tube (ETT) management is an essential technique in handling mice
      with mechanical ventilators. Malposition into bronchi causes not only lethal
      complications for them but also less efficient mechanical ventilation. However,
      in general, it is difficult to know whether the ETT is placed with appropriate
      depth into the trachea of mice. We measured the distance from incisors to the
      bifurcation of trachea of multiple mice, and created a new estimation formula to
      obtain the suitable ETT length for mice with a body weight range from 17 g to 25
      g: length (mm) = 0.5 * bodyweight (g) + 7. However, millimeter step adjustments
      are impracticable. Thus, slightly shorter than 2 cm (18-20 mm) may be the
      universal ETT length for mice with bodyweight > 17 g. Furthermore, their foot
      size may be a good alternative to predict the individual optimal ETT length for
      mice.

PMID- 29649933
TI  - New fungal infections associated with disease-modifying treatments in MS.

PMID- 29649935
TI  - Polyurethane/nano-hydroxyapatite composite films as osteogenic platforms.
AB  - A wide variety of biomaterials are utilized in tissue engineering to promote cell
      proliferations in vitro or tissue growth in vivo. The combination of cells,
      extracellular matrices, and biocompatible materials may make it possible to grow
      functional living tissues ranging from bone to nerve cells. In bone regeneration,
      polymeric scaffolds can be enhanced by the addition of bioactive materials. To
      this end, this study designed several ratios of polyurethane (PU) and nano
      hydroxyapatite (nHA) composites (PU-nHA ratios: 100/0, 90/10, 80/20, 70/30, 60/40
      w/w). The physical and mechanical properties of these composites and their
      relative cellular compatibility in vitro were determined. The chemical
      composition and crystallinity of the composites were confirmed using X-ray
      diffraction, X-ray photoelectron spectroscopy, and thermogravimetric analyses.
      Atomic force microscopy, nano-indentation, and contact angle measurements were
      used to evaluate surface properties. The results showed a significant increase in
      surface roughness and a decrease in contact angle when the nHA concentration
      increased above 20%, resulting in a significant increase in hydrophilicity. These
      surface property changes influenced cellular behavior when MC 3T3-E1 cells were
      seeded on the composites. All composites were cytocompatible. There was a linear
      increase in cell proliferation on the 80/20 and 70/30 composites only, whereas
      subjective evaluation demonstrated noticeable clusters or nodules of cells
      (considered hallmarks of osteogenic differentiation) in the absence of any
      osteogenic inducers only on the 90/10 and 80/20 composites. Cellular data
      suggests that the 80/20 composite was an optimal environment for cell adhesion,
      proliferation, and, potentially, osteogenic differentiation in vitro.

PMID- 29649936
TI  - Barriers to cervical screening and interest in self-sampling among women who
      actively decline screening.
AB  - OBJECTIVES: Understanding why some women actively decline cervical screening
      could contribute to tailored intervention development. We explored reasons for
      non-participation in cervical screening among women who had made an active
      decision not to attend in the future. We also explored interest in human
      papillomavirus self-sampling. METHODS: In a population-based survey of women in
      Great Britain, home-based computer-assisted interviews were carried out with
      screening eligible women. Women reported their intention to attend for screening
      when next invited. They endorsed predefined barriers to screening and indicated
      their interest in human papillomavirus self-sampling. RESULTS: Women who had
      actively declined screening and those who intended to go but were currently
      overdue (n=543) were included in this analysis. Women who had made an active
      decision not to be screened in the future were more likely to endorse the
      barriers 'I have other more important things to worry about' and to perceive
      screening to be of low relevance based on their sexual behaviour. Most
      participants (70%) indicated that they would be interested in human
      papillomavirus self-sampling. Interest in self-sampling was greater among those
      who reported having had a bad experience of screening in the past, were too busy
      or embarrassed to attend, or would not want a man to carry out the test.
      CONCLUSIONS: Women who had made an active decision not to attend screening felt
      it was of low relevance to them and that they had more important things to worry
      about. Shifting the perceived cost-benefit ratio for these women by offering
      human papillomavirus self-sampling might increase screening participation in this
      group.

PMID- 29649937
TI  - Work Requirements in Medicaid for People With Mental Illnesses and Substance Use
      Disorders.

PMID- 29649938
TI  - Preoperative Physiology, Imaging, and Management of Interrupted Aortic Arch.
AB  - Interrupted aortic arch (IAA) is a rare form of critical neonatal heart disease
      in which there is lack of continuity between the ascending aorta and the
      descending thoracic aorta. In the absence of prenatal diagnosis, patients with
      IAA present in shock when the patent ductus arteriosus closes. Diagnosis can
      generally be made by echocardiography, and initiation of prostaglandin E1
      infusion allows for adequate lower body perfusion prior to surgical repair. Full
      neonatal repair can be achieved with good outcomes in most cases. However, there
      is often underdevelopment of the left ventricular outflow tract and risk for
      later surgical re-intervention. Many patients with IAA, particularly those with
      type B, have DiGeorge syndrome, which has important development implications.

PMID- 29649939
TI  - Participation Patterns of Preschool Children With Intellectual Developmental
      Disabilities.
AB  - We aim to examine the pattern of participation of children with intellectual
      developmental disabilities (IDD) or global developmental delay (GDD) in
      comparison with typically developing preschoolers. In addition, to identify
      environmental and personal factors associated with their participation, 20
      children with mild to moderate GDD or IDD, and 24 age- and gender-matched
      controls, aged 3 to 6 years, were assessed using the Assessment of Preschool
      Children's Participation and the Environmental Restriction Questionnaire.
      Significant differences were found between the groups, both for general scales of
      participation and for each activity area. For the IDD/GDD group, participation
      was significantly negatively correlated with environmental restrictions at home.
      For the control group, participation was correlated with demographic variables.
      Typically developing children participate at a higher frequency and in a more
      diverse range of activities compared with children with IDD/GDD. Associations
      between participation and contextual factors varied depending on the child's
      health condition.

PMID- 29649940
TI  - Editorial.

PMID- 29649941
TI  - Guest Editorial: Revisiting Feetham's Criteria for Research of Families to
      Advance Science and Inform Policy for the Health and Well-Being of Families.

PMID- 29649942
TI  - Blocking Tumor Necrosis Factor-Alpha Expression Prevents Blast-Induced
      Excitatory/Inhibitory Synaptic Imbalance and Parvalbumin-Positive Interneuron
      Loss in the Hippocampus.
AB  - Traumatic brain injury (TBI) is a major cause of neurological disorder and death
      in civilian and military populations. It comprises two components-direct injury
      from the traumatic impact and secondary injury from ensuing neural inflammatory
      responses. Blocking tumor necrosis factor-alpha (TNF-alpha), a central regulator
      of neural inflammation, has been shown to improve functional recovery after TBI.
      However, the mechanisms underlying those therapeutic effects are still poorly
      understood. Here, we examined effects of 3,6'-dithiothalidomide (dTT), a
      potentially therapeutic TNF-alpha inhibitor, in mice with blast-induced TBI. We
      found that blast exposure resulted in elevated expression of TNF-alpha,
      activation of microglial cells, enhanced excitatory synaptic transmission,
      reduced inhibitory synaptic transmission, and a loss of parvalbumin-positive
      (PV+) inhibitory interneurons. Administration of dTT for 5 days after the blast
      exposure completely suppressed blast-induced increases in TNF-alpha
      transcription, largely reversed blasted-induced synaptic changes, and prevented
      PV+ neuron loss. However, blocking TNF-alpha expression by dTT failed to mitigate
      blast-induced microglial activation in the hippocampus, as evidenced by their non
      ramified morphology. These results indicate that TNF-alpha plays a major role in
      modulating neuronal functions in blast-induced TBI and that it is a potential
      target for treatment of TBI-related brain disorders.

PMID- 29649943
TI  - 2017 Reviewer Thank You.

PMID- 29649944
TI  - Visuospatial bootstrapping: Binding useful visuospatial information during verbal
      working memory encoding does not require set-shifting executive resources.
AB  - Immediate serial recall of digits is better when the digits are shown by
      highlighting them in a familiar array, such as a phone keypad, compared with
      presenting them serially in a single location, a pattern referred to as
      "visuospatial bootstrapping." This pattern implies the establishment of temporary
      links between verbal and spatial working memory, alongside access to information
      in long-term memory. However, the role of working memory control processes like
      those implied by the "Central Executive" in bootstrapping has not been directly
      investigated. Here, we report a study addressing this issue, focusing on
      executive processes of attentional shifting. Tasks in which information has to be
      sequenced are thought to be heavily dependent on shifting. Memory for digits
      presented in keypads versus single locations was assessed under two secondary
      task load conditions, one with and one without a sequencing requirement, and
      hence differing in the degree to which they invoke shifting. Results provided
      clear evidence that multimodal binding (visuospatial bootstrapping) can operate
      independently of this form of executive control process.

PMID- 29649945
TI  - The priming function of in-car audio instruction.
AB  - Studies to date have focused on the priming power of visual road signs, but not
      the priming potential of audio road scene instruction. Here, the relative priming
      power of visual, audio, and multisensory road scene instructions was assessed. In
      a lab-based study, participants responded to target road scene turns following
      visual, audio, or multisensory road turn primes which were congruent or
      incongruent to the primes in direction, or control primes. All types of
      instruction (visual, audio, and multisensory) were successful in priming
      responses to a road scene. Responses to multisensory-primed targets (both audio
      and visual) were faster than responses to either audio or visual primes alone.
      Incongruent audio primes did not affect performance negatively in the manner of
      incongruent visual or multisensory primes. Results suggest that audio
      instructions have the potential to prime drivers to respond quickly and safely to
      their road environment. Peak performance will be observed if audio and visual
      road instruction primes can be timed to co-occur.

PMID- 29649946
TI  - Does social presence or the potential for interaction reduce social gaze in
      online social scenarios? Introducing the "live lab" paradigm.
AB  - Research has shown that people's gaze is biased away from faces in the real world
      but towards them when they are viewed onscreen. Non-equivalent stimulus
      conditions may have represented a confound in this research, however, as
      participants viewed onscreen stimuli as pre-recordings where interaction was not
      possible compared with real-world stimuli which were viewed in real time where
      interaction was possible. We assessed the independent contributions of online
      social presence and ability for interaction on social gaze by developing the
      "live lab" paradigm. Participants in three groups ( N = 132) viewed a confederate
      as (1) a live webcam stream where interaction was not possible (one-way), (2) a
      live webcam stream where an interaction was possible (two-way), or (3) a pre
      recording. Potential for interaction, rather than online social presence, was the
      primary influence on gaze behaviour: participants in the pre-recorded and one-way
      conditions looked more to the face than those in the two-way condition,
      particularly, when the confederate made "eye contact." Fixation durations to the
      face were shorter when the scene was viewed live, particularly, during a bid for
      eye contact. Our findings support the dual function of gaze but suggest that
      online social presence alone is not sufficient to activate social norms of civil
      inattention. Implications for the reinterpretation of previous research are
      discussed.

PMID- 29649947
TI  - The time to remember: Temporal compression and duration judgements in memory for
      real-life events.
AB  - Recent studies suggest that the continuous flow of information that constitutes
      daily life events is temporally compressed in episodic memory, yet the
      characteristics and determinants of this compression mechanism remain unclear.
      This study examined this question using an experimental paradigm incorporating
      wearable camera technology. Participants experienced a series of real-life events
      and were later asked to mentally replay various event sequences that were cued by
      pictures taken during the original events. Estimates of temporal compression (the
      ratio of the time needed to mentally re-experience an event to the actual event
      duration) showed that events were replayed, on average, about eight times faster
      than the original experiences. This compression mechanism seemed to operate by
      representing events as a succession of moments or slices of prior experience
      separated by temporal discontinuities. Importantly, however, rates of temporal
      compression were not constant and were lower for events involving goal-directed
      actions. The results also showed that the perceived duration of events increased
      with the density of recalled moments of prior experience. Taken together, these
      data extend our understanding of the mechanisms underlying the temporal
      compression and perceived duration of real-life events in episodic memory.

PMID- 29649949
TI  - Postprandial effects of breakfast glycaemic index on cognitive performance among
      young, healthy adults: A crossover clinical trial.
AB  - OBJECTIVE: To evaluate the postprandial effects of high and low glycaemic index
      (GI) breakfasts on cognitive performance in young, healthy adults. METHODS: A
      crossover clinical trial including 40 young, healthy adults (aged 20-40 years,
      50% females) recruited from primary healthcare centres in Salamanca, Spain.
      Verbal memory, phonological fluency, attention, and executive functions were
      examined 0, 60, and 120 minutes after consuming a low GI (LGI), high GI (HGI), or
      water breakfast. Every subject tried each breakfast variant, in a randomized
      order, separated by a washout period of 7 days, for a total of 3 weeks. RESULTS:
      A significant interaction between the type of breakfast consumed and immediate
      verbal memory was identified (P<.05). We observed a trend towards better
      performance in verbal memory (delayed and immediate), attention, and phonological
      fluency following an LGI breakfast. DISCUSSION: Cognitive performance during the
      postprandial phase in young, healthy adults was minimally affected by the GI of
      breakfast. The potential for breakfast's GI modulation to improve short- and long
      term cognitive functioning requires further research.

PMID- 29649950
TI  - Scrotal skin nodule: sebaceous cyst or tuberculosis? A lesson learnt!
AB  - Tuberculosis (TB) is a great mimic of many diseases and may present a dilemma in
      diagnosis. Sebaceous cyst is the commonest swelling that occurs in the scrotal
      skin. We present a 23-year-old patient who presented with a painful hard scrotal
      skin nodule, clinically diagnosed to be an infected calcified sebaceous cyst,
      excised and reported to be due to TB. Nodular scrotal skin TB is extremely rare
      but should nonetheless be considered as a differential diagnosis in regions where
      it is prevalent. Thus, excision of any suspicious nodule is indicated.

PMID- 29649951
TI  - Biliary ascariasis presenting with gangrenous perforation of the gall bladder:
      report of a case and brief review of literature.
AB  - The most common cause of gallbladder perforation is calculous cholecystitis.
      Rarer causes include trauma, iatrogenic injuries, biliary stasis and gall bladder
      ischemia. We report a case of gall bladder gangrene with perforation, secondary
      to extensive ascariasis. A 45-year-old woman presented with acute intestinal
      obstruction and jaundice. She had abdominal distension and right hypochondrial
      tenderness. Abdominal radiography showed dilated bowel loops and ultrasonogram
      showed worms in the small intestine and biliary tree. On exploration, a bolus of
      worms 2 feet proximal to the ileocaecal junction was found causing obstruction.
      Worms were also present in the bile duct and gallbladder causing gangrene and
      perforation. She underwent cholecystectomy, bile-duct exploration and enterotomy.
      However, she died on the third postoperative day of overwhelming sepsis. Enteric
      complications of ascaris leading to bowel obstruction are well-known.
      Hepatobiliary complications such as cholangitis and obstructive jaundice are
      rare. However, such an extreme degree of infestation leading to gangrene and
      perforation of the gall bladder is extremely rare.

PMID- 29649948
TI  - Women's sexual dysfunction associated with psychiatric disorders and their
      treatment.
AB  - Impairment of mental health is the most important risk factor for female sexual
      dysfunction. Women living with psychiatric illness, despite their frequent sexual
      difficulties, consider sexuality to be an important aspect of their quality of
      life. Antidepressant and antipsychotic medication, the neurobiology and symptoms
      of the illness, past trauma, difficulties in establishing relationships and
      stigmatization can all contribute to sexual dysfunction. Low sexual desire is
      strongly linked to depression. Lack of subjective arousal and pleasure are linked
      to trait anxiety: the sensations of physical sexual arousal may lead to fear
      rather than to pleasure. The most common type of sexual pain is 10 times more
      common in women with previous diagnoses of anxiety disorder. Clinicians often do
      not routinely inquire about their patients' sexual concerns, particularly in the
      context of psychotic illness but careful assessment, diagnosis and explanation of
      their situation is necessary and in keeping with patients' wishes. Evidence-based
      pharmacological and non-pharmacological interventions are available but poorly
      researched in the context of psychotic illness.

PMID- 29649952
TI  - Cefquinome-loaded microsphere formulations against Klebsiella pneumonia infection
      during experimental infections.
AB  - The aim of this study was to prepare cefquinome-loaded polylactic acid
      microspheres and to evaluate their in vitro and in vivo characteristics and
      pharmacodynamics for the therapy of pneumonia in a rat model. Microspheres were
      prepared using a 0.7 mm two-fluid nozzle spray drier in one step resulting in
      spherical and smooth microspheres of uniform size (9.8 +/- 3.6 MUm). The
      encapsulation efficiency and drug loading of cefquinome were 91.6 +/- 2.6% and
      18.7 +/- 1.2%, respectively. In vitro release of cefquinome from the microspheres
      was sustained for 36 h. Cefquinome-loaded polylactic acid microspheres as a drug
      delivery system was successful for clearing experimental Klebsiella pneumonia
      lung infections. A decrease in inflammatory cells and an inhibition of
      inflammatory cytokines TNF-alpha, IL-1beta and IL-8 after microspheres treatment
      was found. Changes in cytokine levels and types are secondary manifestations of
      drug bactericidal effects. Rats were considered to be microbiologically cured
      because the bacterial load was less than 100 CFU/g. These results also indicated
      that the spray-drying method of loading therapeutic drug into polylactic acid
      microspheres is a straightforward and safe method for lung-targeting therapy in
      animals.

PMID- 29649953
TI  - Prevalence and variables associated with an abnormal ankle-brachial index among
      patients with human immunodeficiency virus/acquired immunodeficiency syndrome.
AB  - : Objectives The longer survival of patients with human immunodeficiency
      virus/acquired immunodeficiency syndrome and the introduction of the highly
      active antiretroviral therapy have increased the number of chronic conditions;
      among these, cardiovascular diseases. The aim of this study is to determine
      patient, disease, and factors associated with peripheral arterial disease in a
      population of patients with human immunodeficiency virus/acquired
      immunodeficiency syndrome. Methods A prospective nested case-control study of a
      cohort of patients with human immunodeficiency virus/acquired immunodeficiency
      syndrome was conducted in a tertiary medical center in Mexico City. A sample size
      of 206 patients was calculated. Medical history, relevant laboratory data,
      peripheral arterial exam, and screening ankle-brachial index tests were obtained.
      Results The prevalence of abnormal ankle-brachial indexes was 20% (42 patients).
      Patient's mean age was 44 years +/-13. The majority (98.5%) were actively
      receiving highly active antiretroviral therapy; active smoking was reported in 55
      (27%), arterial hypertension and type 2 diabetes mellitus were found in 24 (12%)
      and 22 (11%) patients. Median time from the human immunodeficiency virus
      diagnosis was eight years (Interquartile range +/-11); the mean CD4 count was
      481, with a mean viral load of 13,557 copies (SD +/- 69025.27) and 1889.18 (SD +/
      9052.77) for patients with normal and abnormal ankle-brachial index and a median
      of 40 (IQ +/- 2). Viral load ( p = 0.04) and number of years with human
      immunodeficiency virus/acquired immunodeficiency syndrome ( p = 0.04) were
      significantly associated with abnormal ankle-brachial indexes. Conclusions
      Abnormal ankle-brachial index seems to be more frequent in Mexican patients with
      human immunodeficiency virus/acquired immunodeficiency syndrome when compared
      with the general population at the same age. The most important factors
      associated with arterial disease were the viral load and the number of years with
      human immunodeficiency virus/acquired immunodeficiency syndrome. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT02264509.

PMID- 29649954
TI  - Anatomical Considerations and Open Surgery to Treat Juxtarenal Abdominal Aortic
      Aneurysms.
AB  - INTRODUCTION: Historically, the open approach to the abdominal aorta has been
      transperitoneal (TP). In comparison, a retroperitoneal (RP) incision exposes the
      lateral wall of the suprarenal aorta for clamp application and midline structures
      such as the duodenum and pancreas are not encountered. Proximal clamp position
      for open repair of juxtarenal abdominal aortic aneurysm (JR-AAA) is suprarenal,
      supra-superior mesenteric, or supraceliac. While RP and TP approaches have
      previously been compared for physiological reasons, there are currently no
      randomized controlled trials comparing these methods from an anatomical
      perspective. AIMS: The primary aim is to examine the evidence for adopting an RP
      approach for JR-AAA and compare it with TP approach from an anatomical
      perspective. The secondary aim is to assess optimum proximal clamp position and
      its effect on renal function and mortality for the 2 approaches. METHODS/DESIGN:
      Literature was reviewed searching databases Medline and Embase for studies on
      clamp positioning in JR-AAA repair using a TP or RP approach, up to December
      2017. CONCLUSIONS: There is no clear evidence for the optimum cross-clamp
      position for open repair of JR-AAAs. More proximal clamps provide adequate
      operative space with the possible downside of increased afterload leading to
      visceral and renal ischemia. Clamps placed inferior to the superior mesenteric
      artery allow continued bowel and hepatic perfusion with the potential to cause
      trauma to the adjacent aortic branches during application. As far as the optimum
      approach is concerned, many series show a strong trend for RP as a more proximal
      clamp is required. Significant numbers develop renal failure after JR-AAA repair,
      with most recovering fully irrespective of the clamp position.

PMID- 29649955
TI  - Repair of TEVAR-Associated Type A Dissection in the Elderly Is Possible With
      Reasonable Morbidity and Mortality.
AB  - BACKGROUND: Type A aortic dissection (AAD) is a devastating complication of
      thoracic endovascular repair (TEVAR). In elderly patients, surgery for AAD
      carries considerable morbidity and mortality. Repair of AAD after previous TEVAR
      is an even greater challenge as it usually requires the arch to be addressed and
      a preexisting stent graft to be included into the aortic repair. METHODS: A case
      series of 5 elderly patients who presented with acute AAD after previous TEVAR
      was reviewed. In 4 cases, there was retrograde AAD with involvement of the arch
      and stent graft. In 1 patient, intraoperative inspection showed no involvement of
      the arch. Three underwent ascending and subtotal arch replacement in moderate
      hypothermic circulatory arrest with selective cerebral perfusion. In 1 case,
      concomitant tricuspid valve repair was performed. The patient without involvement
      of the arch underwent emergent replacement of the ascending aorta in deep
      hypothermic circulatory arrest, and in the oldest, aged 88 years, surgery was
      limited to wrapping of the ascending aorta as an on-pump beating salvage
      procedure. RESULTS: Four (80%) of 5 patients survived and were discharged after
      an intensive care unit stay of 17.45 +/- 15.98 days and a hospital stay of 26.0
      +/- 10.98 days. Mortality was 20%. All survivors were discharged with appropriate
      rehabilitation potential and without lasting neurological disabilities.

PMID- 29649956
TI  - Improving the compression dewatering of sewage sludge through bioacidification
      conditioning driven by Acidithiobacillus ferrooxidans: dewatering rate vs.
      dewatering extent.
AB  - Prior to mechanical dewatering, sludge conditioning is indispensable to reduce
      the difficulty of sludge treatment and disposal. The effect of bioacidification
      conditioning driven by Acidithiobacillus ferrooxidans LX5 on the dewatering rate
      and extent of sewage sludge during compression dewatering process was
      investigated in this study. The results showed that the bioacidification of
      sludge driven by A. ferrooxidans LX5 simultaneously improved both the sludge
      dewatering rate and extent, which was not attained by physical/chemical
      conditioning approaches, including ultrasonication, microwave, freezing/thawing,
      or by adding the chemical conditioner cationic polyacrylamide (CPAM). During the
      bioacidification of sludge, the decrease in sludge pH induced the damage of
      sludge microbial cell structures, which enhanced the dewatering extent of sludge,
      and the added Fe2+ and the subsequent bio-oxidized Fe3+ effectively flocculated
      the damaged sludge flocs to improve the sludge dewatering rate. In the
      compression dewatering process consisting of filtration and expression stages,
      high removal of moisture and a short dewatering time were achieved during the
      filtration stage and the expression kinetics were also improved because of the
      high elasticity of sludge cake and the rapid creeping of the aggregates within
      the sludge cake. In addition, the usefulness of bioacidification driven by A.
      ferrooxidans LX5 in improving the compression dewatering of sewage sludge could
      not be attained by the chemical treatment of sludge through pH modification and
      Fe3+ addition. Therefore, the bioacidification of sludge driven by A.
      ferrooxidans LX5 is an effective conditioning method to simultaneously improve
      the rate and extent of compression dewatering of sewage sludge.

PMID- 29649957
TI  - Tissue-Engineered Neo-Urinary Conduit from Decellularized Trachea.
AB  - Decellularized tissues have been increasingly popular for constructing scaffolds
      for tissue engineering applications due to their beneficial biological
      compositions and mechanical properties. It is therefore natural to consider
      decellularized trachea for construction of tissue-engineered trachea, as well as
      other tubular organs. A Neo-Urinary Conduit (NUC) is such a tubular organ that
      works as a passage for urine removal in bladder cancer patients who need a
      urinary diversion after their diseased bladder is removed. In this study, we
      report our findings on the feasibility of using a decellularized trachea for NUC
      applications. As a NUC scaffold, decellularized trachea provides benefits of
      having not only naturally occurring biological components but also having
      sufficient mechanical properties and structural integrity. We, therefore,
      decellularized rabbit trachea, evaluated its mechanical performance, and
      investigated its ability to support in vitro growth of human smooth muscle cells
      (hSMCs) and human urothelial cells (hUCs). The decellularized trachea had
      appropriate biomechanical properties with ultimate tensile strength of ~0.34 MPa
      in longitudinal direction and ~1.0 MPa in circumferential direction and resisted
      a radial burst pressure of >155 mm Hg. Cell morphology study by scanning electron
      microscopy further showed that hUCs grown on decellularized trachea adopted a
      typical flatten and interconnected network structure in the lumen of the
      scaffold, while they formed a round spherical shape and did not spread on the
      outer surfaces. SMCs, on the other hand, spread well throughout the scaffold. The
      gene expression analysis by real time quantitative polymerase chain reaction (RT
      qPCR) and immunofluorescence studies further confirmed scaffold's ability to
      support long-term growth of hSMCs. Since uroepithelium has been shown to
      regenerate itself over time in vivo, these findings suggest that it is possible
      to construct a NUC from decellularized trachea without any preseeding of UCs. In
      future, we plan to translate decellularized trachea in a preclinical animal model
      and evaluate its biological performance.

PMID- 29649958
TI  - The nuts and bolts of the Haloferax CRISPR-Cas system I-B.
AB  - Invading genetic elements pose a constant threat to prokaryotic survival,
      requiring an effective defence. Eleven years ago, the arsenal of known defence
      mechanisms was expanded by the discovery of the CRISPR-Cas system. Although
      CRISPR-Cas is present in the majority of archaea, research often focuses on
      bacterial models. Here, we provide a perspective based on insights gained
      studying CRISPR-Cas system I-B of the archaeon Haloferax volcanii. The system
      relies on more than 50 different crRNAs, whose stability and maintenance
      critically depend on the proteins Cas5 and Cas7, which bind the crRNA and form
      the Cascade complex. The interference machinery requires a seed sequence and can
      interact with multiple PAM sequences. H. volcanii stands out as the first example
      of an organism that can tolerate autoimmunity via the CRISPR-Cas system while
      maintaining a constitutively active system. In addition, the H. volcanii system
      was successfully developed into a tool for gene regulation.

PMID- 29649960
TI  - President's Message.

PMID- 29649961
TI  - Family Care/Caring Based on Family Belief Systems Theory.

PMID- 29649959
TI  - Whole Brain Magnetic Resonance Spectroscopic Determinants of Functional Outcomes
      in Pediatric Moderate/Severe Traumatic Brain Injury.
AB  - Diffuse axonal injury contributes to the long-term functional morbidity observed
      after pediatric moderate/severe traumatic brain injury (msTBI). Whole-brain
      proton magnetic resonance echo-planar spectroscopic imaging was used to measure
      the neurometabolite levels in the brain to delineate the course of
      disruption/repair during the first year post-msTBI. The association between
      metabolite biomarkers and functional measures (cognitive functioning and corpus
      callosum [CC] function assessed by interhemispheric transfer time [IHTT] using an
      event related potential paradigm) was also explored. Pediatric patients with
      msTBI underwent assessments at two times (post-acutely at a mean of three months
      post-injury, n = 31, and chronically at a mean of 16 months post-injury, n = 24).
      Healthy controls also underwent two evaluations, approximately 12 months apart.
      Post-acutely, in patients with msTBI, there were elevations in choline (Cho;
      marker for inflammation and/or altered membrane metabolism) in all four brain
      lobes and the CC and decreases in N-acetylaspartate (NAA; marker for neuronal and
      axonal integrity) in the CC compared with controls, all of which normalized by
      the chronic time point. Subgroups of TBI showed variable patterns chronically.
      Patients with slow IHTT had lower lobar Cho chronically than those with normal
      IHTT; they also did not show normalization in CC NAA whereas those with normal
      IHTT showed significantly higher levels of CC NAA relative to controls. In the
      normal IHTT group only, chronic CC Cho and NAA together explained 70% of the
      variance in long-term cognitive functioning. MR based whole brain metabolic
      evaluations show different patterns of neurochemistry after msTBI in two
      subgroups with different outcomes. There is a dynamic relationship between
      prolonged inflammatory responses to brain damage, reparative
      processes/remyelination, and subsequent neurobehavioral outcomes. Multimodal
      studies allow us to test hypotheses about degenerative and reparative processes
      in patient groups that have divergent functional outcome, with the ultimate goal
      of developing targeted therapeutic agents.

PMID- 29649962
TI  - The Mycoheterotrophic Symbiosis Between Orchids and Mycorrhizal Fungi Possesses
      Major Components Shared with Mutualistic Plant-Mycorrhizal Symbioses.
AB  - Achlorophylous and early developmental stages of chorolophylous orchids are
      highly dependent on carbon and other nutrients provided by mycorrhizal fungi, in
      a nutritional mode termed mycoheterotrophy. Previous findings have implied that
      some common properties at least partially underlie the mycorrhizal symbioses of
      mycoheterotrophic orchids and that of autotrophic arbuscular mycorrhizal (AM)
      plants; however, information about the molecular mechanisms of the relationship
      between orchids and their mycorrhizal fungi is limited. In this study, we
      characterized the molecular basis of an orchid-mycorrhizal (OM) symbiosis by
      analyzing the transcriptome of Bletilla striata at an early developmental stage
      associated with the mycorrhizal fungus Tulasnella sp. The essential components
      required for the establishment of mutual symbioses with AM fungi or rhizobia in
      most terrestrial plants were identified from the B. striata gene set. A cross
      species gene complementation analysis showed one of the component genes, calcium
      and calmodulin-dependent protein kinase gene CCaMK in B. striata, retains
      functional characteristics of that in AM plants. The expression analysis revealed
      the activation of homologs of AM-related genes during the OM symbiosis. Our
      results suggest that orchids possess, at least partly, the molecular mechanisms
      common to AM plants.

PMID- 29649963
TI  - Whole-Genome Sequence of the Orchid Anthracnose Pathogen Colletotrichum
      orchidophilum.
AB  - Colletotrichum orchidophilum is a plant-pathogenic fungus infecting a wide range
      of plant species belonging to the family Orchidaceae. In addition to its economic
      impact, C. orchidophilum has been used in recent years in evolutionary studies
      because it represents the closest related species to the C. acutatum species
      complex. Here, we present the first-draft whole-genome sequence of C.
      orchidophilum IMI 309357, providing a resource for future research on anthracnose
      of Orchidaceae and other hosts.

PMID- 29649964
TI  - Gene Expression Profiling Shows That NbFDN1 Is Involved in Modulating the
      Hypersensitive Response-Like Cell Death Induced by the Oat dwarf virus RepA
      Protein.
AB  - In this study, we used high-throughput deep nucleotide sequencing to characterize
      the global transcriptional response of Nicotiana benthamiana plants to transient
      expression of the RepA protein from Oat dwarf virus (ODV). We identified 7,878
      significantly differentially expressed genes (DEG) that mapped to 125 pathways,
      suggesting that comprehensive networks are involved in regulation of RepA-induced
      cell death. Of the 202 DEG associated with photosynthesis, expression of 195 was
      found to be downregulated, indicating a significant inhibition of photosynthesis
      in response to RepA expression, which is associated with chloroplast disruption
      and physiological changes. We focused our analysis on NbFDN1, a member of the
      ferredoxin protein family that participates in the chloroplast electron transport
      chain performing oxygenic photosynthesis, which was identified to directly
      interact with NbTsip1. We separately knocked down the expression of NbFDN1 and
      NbTsip1 using virus-induced gene silencing, and found that NbFDN1 silencing
      speeded up the development of RepA-induced cell death, unlike NbTsip1 silencing,
      which showed an opposite effect on RepA-induced response. Further study showed
      increased H2O2 accumulation and a negative correlation between the transcripts of
      NbFDN1 and NbTsip1 in NbFDN1-silenced plants. Hence, we speculate that NbFDN1 has
      an effect on RepA-induced hypersensitive response-like response by modulating
      NbTsip1 transcription as well as H2O2 production.

PMID- 29649965
TI  - Evaluation of the influence of sprinkling powdered slaked lime on microorganisms
      for the prevention of domestic animal infectious diseases.
AB  - When infectious diseases arise in domestic animals, a large amount of slaked lime
      is sprinkled on cattle sheds and their surroundings for disinfection and
      prevention. However, optimal sprinkling methods, standard and upper limit of
      slaked lime, and influence of slaked lime on non-target microorganisms remain
      unclear. In this study, we clarified detailed microbicidal effects of slaked lime
      via in vitro experiments and the influence of sprinkling powdered slaked lime
      (PSL) in field soil on microorganisms. In vitro disinfection tests assessing the
      appropriate amount of water and ventilation conditions were also performed in
      sterilized glass bottles with soil and Salmonella enterica subsp. enterica
      serovar Typhimurium. Under conditions with a small amount of water relative to
      the amount of PSL, the bactericidal effect and sustainability of powdered slaked
      lime (PSL) tended to be lower than those without spraying water. Moreover, the
      sterilization effect markedly decreased after 7 days under conditions with
      abundant water. These results indicate that the amount of sprayed water is very
      important for the bactericidal effect and persistence of PSL. A field experiment
      showed that the pH and exchange calcium (Ca) content of the soil sprinkled with
      over 1000 g m-2 PSL remained high even after a long period (>=1 year), with
      values of approximately 0.5-1.0 and approximately 3-11 times the level without
      PSL, respectively. However, sprinkling PSL did not influence viable microbial
      counts at any concentration.

PMID- 29649966
TI  - A Systematic Review of Intimate Partner Violence Interventions: State of the
      Field and Implications for Practitioners.
AB  - Intimate partner violence (IPV) victimization is a global public health issue and
      has serious consequences of women's health. While scholars and researchers have
      made some progress in addressing IPV and its impact across different levels of
      care, there is a paucity of intervention research in this area. For example, we
      know little about which intervention models work best for particular groups of
      IPV survivors. Previous reviews have concluded there is insufficient evidence to
      recommend specific treatment options for victims, but they have also been limited
      in scope of target populations or have employed narrow eligibility criteria. This
      systematic review examined the efficacy and effectiveness of interventions for
      victims of IPV related to physical and mental health and revictimization. Three
      large databases were searched and articles were selected using specified
      criteria. Fifty-seven articles met inclusion criteria. Results indicate that both
      empowerment-based advocacy and cognitively focused clinical interventions
      demonstrate positive outcomes on the vast sequelae of violence in the context of
      an intimate relationship. The heterogeneity of intervention approaches and
      frameworks makes comparisons across studies challenging, but this review
      demonstrates that interventions focused on problem-solving/solution seeking,
      enhanced choice making and the alteration in distorted self-thinking and
      perception are promising in facilitating and maintaining positive physical and
      mental health changes for women who experience violence.

PMID- 29649967
TI  - Influence of maternal and own genotype at tanning dependence-related SNPs on sun
      exposure in childhood.
AB  - BACKGROUND: Research suggests there may be a genetic influence on the likelihood
      of becoming tanning dependent (TD). The way in which mothers regulate their
      children's sun exposure may be affected by being TD. We investigated the
      associations between single nucleotide polymorphisms (SNPs) related to being TD
      and early sun exposure. METHODS: Data from the Avon Longitudinal Study of Parents
      and Children (ALSPAC) were used. Associations between 17 TD related SNPs in
      children and their mothers and 10 sun exposure variables in children (assessed
      via questionnaire at age 8) were analyzed in logistic and ordinal logistic
      regressions. Analyses were adjusted for principal components of population
      structure and age (at time of questionnaire response). Models with additional
      adjustment for maternal or offspring genotypes were also tested. Secondary
      analyses included adjustment for sex and skin pigmentation. RESULTS: Among ALSPAC
      children, the rs29132 SNP in the Vesicle-associated membrane protein-associated
      protein A (VAPA) gene was associated with five sun exposure variables whilst the
      rs650662 SNP in the Opioid Receptor Mu 1 (OPRM1) gene was associated with three.
      The remaining SNPs did not show associations beyond what was expected by chance.
      After Bonferroni correction one SNP in the children was associated with an
      increased likelihood of using sun cream whilst in the sun at 8 years old
      (rs60050811 in the Spermatogenesis and Centriole Associated 1 (SPATC1) gene, OR
      per C allele = 1.34, 95% CI 1.11-1.62, p = .003). In the mothers, rs650662 in
      OPRM1 was associated with the use of a lower factor of sun cream in their
      children, (OR per A allele = 0.89, 95% CI 0.82-0.96, p = .002). Whilst rs2073478
      in the Aldehyde Dehydrogenase 1 Family Member B1 (ALDH1B1) gene was associated
      with a reduced odds of their child using a sun block or cream with a 4 star
      rating (OR per T allele = 0.68, 95% CI 0.53-0.88, p = .003). Similar but weaker
      associations were observed for the main findings in the secondary analyses.
      CONCLUSIONS: We found weak evidence to suggest that genes previously associated
      with TD are associated with sun exposure in children of European ancestry from
      southwest England.

PMID- 29649968
TI  - Swimming exercise to control precocious maturation in male seabass (Dicentrarchus
      labrax).
AB  - BACKGROUND: Male European seabass, already predominant (~ 70%) in cultured
      stocks, show a high incidence (20-30%) of precocious sexual maturation under
      current aquaculture practices, leading to important economic losses for the
      industry. In view of the known modulation of reproductive development by swimming
      exercise in other teleost species, we aimed at investigating the effects of
      sustained swimming on reproductive development in seabass males during the first
      year of life in order to determine if swimming could potentially reduce
      precocious sexual maturation. METHODS: Pre-pubertal seabass (3.91 +/- 0.22 g of
      body weight (BW)) were subjected to a 10 week swimming regime at their optimal
      swimming speed (Uopt) in an oval-shaped Brett-type flume or kept at rest during
      this period. Using Blazka-type swim tunnels, Uopt was determined three times
      during the course of the experiment: 0.66 m s- 1 at 19 +/- 1 g BW, 10.2 +/- 0.2
      cm of standard length (SL) (week 1); 0.69 m s- 1 at 38 +/- 3 g BW, 12.7 +/- 0.3
      cm SL (week 5), and also 0.69 m s- 1 at 77 +/- 7 g BW, 15.7 +/- 0.5 cm SL (week
      9). Every 2 weeks, size and gonadal weight were monitored in the exercised (N =
      15) and non-exercised fish (N = 15). After 10 weeks, exercised and non-exercised
      males were sampled to determine plasma 11-ketotestosterone levels, testicular
      mRNA expression levels of genes involved in steroidogenesis and gametogenesis by
      qPCR, as well as the relative abundance of germ cells representing the different
      spermatogenic stages by histological examination. RESULTS: Our results indicate
      that sustained swimming exercise at Uopt delays testicular development in male
      European seabass as evidenced by decreased gonado-somatic index, slower
      progression of testicular development and by reduced mRNA expression levels of
      follicle stimulating hormone receptor (fshR), 3-beta-hydroxysteroid dehydrogenase
      (3betahsd), 11-beta hydroxysteroid dehydrogenase (11betahsd), estrogen receptor
      beta (erbeta2), anti-mullerian hormone (amh), structural maintenance of
      chromosomes protein 1B (smc1beta), inhibin beta A (inhba) and gonado-somal
      derived factor 1 (gsdf1) in exercised males as compared with the non-exercised
      males. CONCLUSIONS: Swimming exercise may represent a natural and non-invasive
      tool to reduce the incidence of sexually precocious males in seabass aquaculture.

PMID- 29649969
TI  - Magnetic resonance imaging for assessment of cerebrovascular reactivity and its
      relationship to cognition: a systematic review.
AB  - BACKGROUND: Cerebrovascular reactivity (CVR) refers to the responsiveness of
      cerebral vasculature to vasoactive stimuli. CVR is an indicator of brain health
      and can be assessed using vasodilatory techniques and magnetic resonance imaging
      (MRI). Using such approaches, some researchers have explored the relationship
      between CVR and cognition; here we systematically review this work. RESULTS: We
      extracted information pertaining to: (1) study location and design, participant
      characteristics, sample sizes, (2) design of vascular challenge, end-tidal CO 2
      (etCO 2 ) concentrations (if applicable), (3) MRI protocol, (4) cognitive
      assessment, (5) CVR values, and outcomes of statistical analyses with cognitive
      tests. Five studies assessed participants with cognitive impairment compared to
      controls, one studied patients with multiple sclerosis with or without cognitive
      impairment compared to controls, one examined patients with moyamoya disease with
      or without cognitive impairment, two investigated patients with Type 2 diabetes
      mellitus (T2DM), and one was a cross-sectional study with younger and older
      healthy adults. Cognition was typically probed using the MMSE and tests of
      executive function, while a number of vasodilatory techniques were employed.
      CONCLUSION: CVR was associated with cognition in six of ten studies, but
      heterogeneity of study samples, designs and vasodilatory methods may have a role
      in the inconsistent findings. We make recommendations for future research that
      includes use of a multi-domain cognitive assessment and standardised hypercapnic
      challenge with MRI.

PMID- 29649970
TI  - Correction to: Genetic characterization of Bacillus anthracis in Guizhou
      Province, Southwest of China.
AB  - ERRATUM: Upon publication of the original article (1) it was highlighted by the
      authors that a grant awarded to support the research work of the study was missed
      in the acknowledgements. It should also be acknowledged that the grant titled
      "Genotyping and Molecular Epidemiological Characteristic of Bacillus anthracis in
      Guizhou Province" awarded by the Program of Natural Science Foundation of Guizhou
      Province (Grant No. Qian Ke He J Word [2015] 2084)also contributed to the
      resources for this research. This has since been formally noted in this
      correction article.

PMID- 29649971
TI  - Realizing drug repositioning by adapting a recommendation system to handle the
      process.
AB  - BACKGROUND: Drug repositioning is the process of identifying new targets for
      known drugs. It can be used to overcome problems associated with traditional drug
      discovery by adapting existing drugs to treat new discovered diseases. Thus, it
      may reduce associated risk, cost and time required to identify and verify new
      drugs. Nowadays, drug repositioning has received more attention from industry and
      academia. To tackle this problem, researchers have applied many different
      computational methods and have used various features of drugs and diseases.
      RESULTS: In this study, we contribute to the ongoing research efforts by
      combining multiple features, namely chemical structures, protein interactions and
      side-effects to predict new indications of target drugs. To achieve our target,
      we realize drug repositioning as a recommendation process and this leads to a new
      perspective in tackling the problem. The utilized recommendation method is based
      on Pareto dominance and collaborative filtering. It can also integrate multiple
      data-sources and multiple features. For the computation part, we applied several
      settings and we compared their performance. Evaluation results show that the
      proposed method can achieve more concentrated predictions with high precision,
      where nearly half of the predictions are true. CONCLUSIONS: Compared to other
      state of the art methods described in the literature, the proposed method is
      better at making right predictions by having higher precision. The reported
      results demonstrate the applicability and effectiveness of recommendation methods
      for drug repositioning.

PMID- 29649972
TI  - Exploring barriers to the use of formal maternal health services and priority
      areas for action in Sidama zone, southern Ethiopia.
AB  - BACKGROUND: In 2015 the maternal mortality ratio for Ethiopia was 353 per 100,000
      live births. Large numbers of women do not use maternal health services. This
      study aimed to identify factors influencing the use of maternal health services
      at the primary health care unit (PHCU) level in rural communities in Sidama zone,
      south Ethiopia in order to design quality improvement interventions. METHODS: We
      conducted a qualitative study in six woredas in 2013: 14 focus group discussions
      (FGDs) and 44 in-depth interviews with purposefully selected community members
      (women, male, traditional birth attendants, local kebele administrators), health
      professionals and health extension workers (HEWs) at PHCUs. We digitally
      recorded, transcribed and thematically analysed the interviews and FGDs using
      Nvivo. The 'three delay model' informed the analytical process and discussion of
      barriers to the use of maternal health services. RESULTS: Lack of knowledge on
      danger signs and benefits of maternal health services; cultural and traditional
      beliefs; trust in TBAs; lack of decision making power of women, previous negative
      experiences with health facilities; fear of going to an unfamiliar setting; lack
      of privacy and perceived costs of maternal health services were the main factors
      causing the first delay in deciding to seek care. Transport problems in
      inaccessible areas were the main contributing factor for the second delay on
      reaching care facilities. Lack of logistic supplies and equipment, insufficient
      knowledge and skills and unprofessional behaviour of health workers were key
      factors for the third delay in accessing quality care. CONCLUSIONS: Use of
      maternal health services at the PHCU level in Sidama zone is influenced by
      complex factors within the community and health system. PHCUs should continue to
      implement awareness creation activities to improve knowledge of the community on
      complications of pregnancy and benefits of maternal health services. The health
      system has to be responsive to community's cultural norms and practices. The
      mangers of the woreda health office and health centres should take into account
      the available budgets; work on ensuring the necessary logistics and supplies to
      be in place at PHCU.

PMID- 29649973
TI  - Clinical and histological evolution after de novo donor-specific anti-human
      leukocyte antigen antibodies: a single centre retrospective study.
AB  - BACKGROUND: Donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA)
      can be preformed or de novo (dn). Strategies to manage preformed DSA are well
      described, but data on the management and outcomes of dnDSA are lacking. METHODS:
      We performed a retrospective analysis of data from a single centre of the
      management and outcomes of 22 patients in whom a dnDSA was identified with
      contemporary and follow up biopsies. RESULTS: Evolution from baseline to follow
      up revealed a statistically significant loss of kidney function (estimated
      glomerular filtration rate: 45.9 +/- 16.7 versus 37.4 +/- 13.8 ml/min/1.73 m2; p
      = 0.005) and increase in the proportion of patients with transplant
      glomerulopathy (percentage with cg lesion >=1: 27.2% vs. 45.4%; p = 0.04). Nine
      patients were not treated at the time of dnDSA identification, and 13 patients
      received various drug combinations (e.g., corticosteroids, plasmapheresis,
      thymoglobulins and/or rituximab). No significant pathological changes were
      observed for the various treatment combinations. CONCLUSION: Our retrospective
      analysis of a small sample suggests that dnDSA should be considered a risk factor
      for the loss of kidney function independent of the baseline biopsy, and
      multidisciplinary evaluations of the transplant patient are a necessary
      requirement. Further confirmation in a multicentre prospective trial is required.

PMID- 29649974
TI  - Delayed and repeated intranasal delivery of bone marrow stromal cells increases
      regeneration and functional recovery after ischemic stroke in mice.
AB  - BACKGROUND: Stroke is a leading cause of death and disability worldwide, yet
      there are limited treatments available. Intranasal administration is a novel non
      invasive strategy to deliver cell therapy into the brain. Cells delivered via the
      intranasal route can migrate from the nasal mucosa to the ischemic infarct and
      show acute neuroprotection as well as functional benefits. However, there is
      little information about the regenerative effects of this transplantation method
      in the delayed phase of stroke. We hypothesized that repeated intranasal
      deliveries of bone marrow stromal cells (BMSCs) would be feasible and could
      enhance delayed neurovascular repair and functional recovery after ischemic
      stroke. RESULTS: Reverse transcription polymerase chain reaction and
      immunocytochemistry were performed to analyze the expression of regenerative
      factors including SDF-1alpha, CXCR4, VEGF and FAK in BMSCs. Ischemic stroke
      targeting the somatosensory cortex was induced in adult C57BL/6 mice by
      permanently occluding the right middle cerebral artery and temporarily occluding
      both common carotid arteries. Hypoxic preconditioned (HP) BMSCs (HP-BMSCs) with
      increased expression of surviving factors HIF-1alpha and Bcl-xl (1 * 106
      cells/100 MUl per mouse) or cell media were administered intranasally at 3, 4, 5,
      and 6 days after stroke. Mice received daily BrdU (50 mg/kg) injections until
      sacrifice. BMSCs were prelabeled with Hoechst 33342 and detected within the peri
      infarct area 6 and 24 h after transplantation. In immunohistochemical staining,
      significant increases in NeuN/BrdU and Glut-1/BrdU double positive cells were
      seen in stroke mice received HP-BMSCs compared to those received regular BMSCs.
      HP-BMSC transplantation significantly increased local cerebral blood flow and
      improved performance in the adhesive removal test. CONCLUSIONS: This study
      suggests that delayed and repeated intranasal deliveries of HP-treated BMSCs is
      an effective treatment to encourage regeneration after stroke.

PMID- 29649975
TI  - Characterising resuscitation promoting factor fluorescent-fusions in
      mycobacteria.
AB  - BACKGROUND: Resuscitation promoting factor proteins (Rpfs) are peptidoglycan
      glycosidases capable of resuscitating dormant mycobacteria, and have been found
      to play a role in the pathogenesis of tuberculosis. However, the specific roles
      and localisation of each of the 5 Rpfs in Mycobacterium tuberculosis remain
      mostly unknown. In this work our aim was to construct fluorescent fusions of M.
      tuberculosis Rpf proteins as tools to investigate their function. RESULTS: We
      found that Rpf-fusions to the fluorescent protein mCherry are functional and able
      to promote cell growth under different conditions. However, fusions to Enhanced
      Green Fluorescent Protein (EGFP) were non-functional in the assays used and none
      were secreted into the extracellular medium, which suggests Rpfs may be secreted
      via the Sec pathway. No specific cellular localization was observed for either
      set of fusions using time-lapse video microscopy. CONCLUSIONS: We present the
      validation and testing of five M. tuberculosis Rpfs fused to mCherry, which are
      functional in resuscitation assays, but do not show any specific cellular
      localisation under the conditions tested. Our results suggest that Rpfs are
      likely to be secreted via the Sec pathway. We propose that such mCherry fusions
      will be useful tools for the further study of Rpf localisation, individual
      expression, and function.

PMID- 29649976
TI  - Identification of a novel nonsense mutation in SH2D1A in a patient with X-linked
      lymphoproliferative syndrome type 1: a case report.
AB  - BACKGROUND: X-linked lymphoproliferative syndrome type 1 (XLP1) is an X-linked
      recessive genetic disorder with a strong resemblance to hemophagocytic
      lymphohistiocytosis (HLH). Causative mutations for XLP1 have been identified in
      SH2D1A, located on chromosome Xq25. CASE PRESENTATION: We report a case of an 18
      month-old male with a novel nonsense mutation in SH2D1A. The patient presented
      the typical phenotype of HLH, including splenomegaly and hemophagocytosis in the
      bone marrow. Thus, he was initially diagnosed with HLH based on HLH-2004
      guidelines. High-throughput amplicon sequencing was performed to detect mutations
      in the most commonly reported causative genes of HLH, i.e., PRF1, UNC13D, STX11,
      STXBP2, SH2D1A, and XIAP. A likely pathogenic nonsense mutation was detected in
      SH2D1A (NM_002351.4:c.300T>A). The mutation was inherited from the patient's
      mother, and an X-linked recessive mode of inheritance was confirmed by a two
      generation pedigree analysis based on Sanger sequencing results. CONCLUSIONS: The
      nonsense mutation in SH2D1A (NM_002351.4:c.300T>A) was reported for the first
      time in a case of XLP1 and was considered to be likely pathogenic based on the
      truncation of the mRNA sequence. This finding expands the spectrum of known XLP
      related mutations in Chinese patients and indicates the utility of amplicon
      sequencing for XLP and HLH diagnosis.

PMID- 29649977
TI  - Development of fine motor skills is associated with expressive language outcomes
      in infants at high and low risk for autism spectrum disorder.
AB  - BACKGROUND: A growing body of research suggests that fine motor abilities are
      associated with skills in a variety of domains in both typical and atypical
      development. In this study, we investigated developmental trajectories of fine
      motor skills between 6 and 24 months in relation to expressive language outcomes
      at 36 months in infants at high and low familial risk for autism spectrum
      disorder (ASD). METHODS: Participants included 71 high-risk infants without ASD
      diagnoses, 30 high-risk infants later diagnosed with ASD, and 69 low-risk infants
      without ASD diagnoses. As part of a prospective, longitudinal study, fine motor
      skills were assessed at 6, 12, 18, and 24 months of age and expressive language
      outcomes at 36 months using the Mullen Scales of Early Learning. Diagnosis of ASD
      was determined at the infant's last visit to the lab (18, 24, or 36 months) using
      the Autism Diagnostic Observation Schedule. RESULTS: Hierarchical linear modeling
      revealed that high-risk infants who later developed ASD showed significantly
      slower growth in fine motor skills between 6 and 24 months, compared to their
      typically developing peers. In contrast to group differences in growth from age 6
      months, cross-sectional group differences emerged only in the second year of
      life. Also, fine motor skills at 6 months predicted expressive language outcomes
      at 3 years of age. CONCLUSIONS: These results highlight the importance of
      utilizing longitudinal approaches in measuring early fine motor skills to reveal
      subtle group differences in infancy between ASD high-risk and low-risk infant
      populations and to predict their subsequent language outcomes.

PMID- 29649978
TI  - Personalized objects can optimize the diagnosis of EMCS in the assessment of
      functional object use in the CRS-R: a double blind, randomized clinical trial.
AB  - BACKGROUND: Behavioral assessment has been acted as the gold standard for the
      diagnosis of disorders of consciousness (DOC) patients. The item "Functional
      Object Use" in the motor function sub-scale in the Coma Recovery Scale-Revised
      (CRS-R) is a key item in differentiating between minimally conscious state (MCS)
      and emergence from MCS (EMCS). However, previous studies suggested that certain
      specific stimuli, especially something self-relevant can affect DOC patients'
      scores of behavioral assessment scale. So, we attempted to find out if
      personalized objects can improve the diagnosis of EMCS in the assessment of
      Functional Object Use by comparing the use of patients' favorite objects and
      other common objects in MCS patients. METHODS: Twenty-one post-comatose patients
      diagnosed as MCS were prospectively included. The item "Functional Object Use"
      was assessed by using personalized objects (e.g., cigarette, paper) and non
      personalized objects, which were presented in a random order. The rest
      assessments were performed following the standard protocol of the CRS-R. The
      differences between functional uses of the two types of objects were analyzed by
      the McNemar test. RESULTS: The incidence of Functional Object Use was
      significantly higher using personalized objects than non-personalized objects in
      the CRS-R. Five out of the 21 MCS studied patients, who were assessed with non
      personalized objects, were re-diagnosed as EMCS with personalized objects (chi2 =
      5, df = 1, p < 0.05). CONCLUSIONS: Personalized objects employed here seem to be
      more effective to elicit patients' responses as compared to non-personalized
      objects during the assessment of Functional Object Use in DOC patients. TRIAL
      REGISTRATION: Clinical Trials.gov: NCT02988206 ; Date of registration:
      2016/12/12.

PMID- 29649979
TI  - Ginseng Genome Database: an open-access platform for genomics of Panax ginseng.
AB  - BACKGROUND: The ginseng (Panax ginseng C.A. Meyer) is a perennial herbaceous
      plant that has been used in traditional oriental medicine for thousands of years.
      Ginsenosides, which have significant pharmacological effects on human health, are
      the foremost bioactive constituents in this plant. Having realized the importance
      of this plant to humans, an integrated omics resource becomes indispensable to
      facilitate genomic research, molecular breeding and pharmacological study of this
      herb. DESCRIPTION: The first draft genome sequences of P. ginseng cultivar
      "Chunpoong" were reported recently. Here, using the draft genome, transcriptome,
      and functional annotation datasets of P. ginseng, we have constructed the Ginseng
      Genome Database http://ginsengdb.snu.ac.kr /, the first open-access platform to
      provide comprehensive genomic resources of P. ginseng. The current version of
      this database provides the most up-to-date draft genome sequence (of
      approximately 3000 Mbp of scaffold sequences) along with the structural and
      functional annotations for 59,352 genes and digital expression of genes based on
      transcriptome data from different tissues, growth stages and treatments. In
      addition, tools for visualization and the genomic data from various analyses are
      provided. All data in the database were manually curated and integrated within a
      user-friendly query page. CONCLUSION: This database provides valuable resources
      for a range of research fields related to P. ginseng and other species belonging
      to the Apiales order as well as for plant research communities in general.
      Ginseng genome database can be accessed at http://ginsengdb.snu.ac.kr /.

PMID- 29649980
TI  - Patterns of caesarean section in HIV infected and non-infected women in Malawi:
      is caesarean section used for PMTCT?
AB  - BACKGROUND: Caesarean section (CS) is not recommended for PMTCT in Malawi HIV
      Guidelines, contrary to most high-income countries where CS is indicated if viral
      suppression is sub-optimal pre-delivery. We describe patterns of CS in HIV
      infected and uninfected women in Malawi and explored if insight into the use of
      Elective CS (ECS) for PMTCT could be obtained. METHODS: We used routinely
      collected data from individual medical records from 17 large health facilities in
      the central and southern regions of Malawi, from January 2010 to December 2013.
      We included data from maternity registers from all HIV-positive women, and
      randomly selected around every fourth woman with negative or unknown HIV status.
      We used multivariable logistic regressions and cluster-based robust standard
      errors to examine independent associations of patient- and facility
      characteristics with CS and ECS. RESULTS: We included 62,033 women in the
      analysis. The weighted percentage of women who had a spontaneous vaginal delivery
      was 80.0% (CI 95% 79.5-80.4%); 2.4% (95% CI 2.3-2.6%) had a vacuum extraction;
      2.3% (95% CI 2.2-2.5%) had a vaginal breech delivery; 14.0% (95% CI 13.6-14.4%)
      had a CS while for 1.3% (95% CI 1.2-1.4%) the mode of delivery was not recorded.
      Prevalence of CS without recorded medical or obstetric indication (ECS) was 5.1%,
      (n = 3152). Presence of maternal and infant complications and older age were
      independently associated with CS delivery. HIV-positive women were less likely to
      have ECS than HIV negative women (aOR 0.65; 95%-CI 0.57-0.74). Among HIV-positive
      women, those on antiretrovirals (ARV's) for >=4 weeks prior to delivery were less
      likely to have ECS than HIV-positive women who had not received ARVs during
      pregnancy (aOR 0.81; 95% CI 0.68-0.96). CONCLUSIONS: The pattern of CS's in
      Malawi is largely determined by maternal and infant complications. Positive HIV
      status was negatively associated with CS delivery, possibly because health care
      workers were concerned about the risk of occupational HIV transmission and the
      known increased risk of post-operative complications. Our results leave open the
      possibility that CS is practiced to prevent MTCT given that ECS was more common
      among women at high risk of MTCT due to no or short exposure to ARV's.

PMID- 29649982
TI  - Identification and characterization of a novel 43-bp deletion mutation of the
      ATP7B gene in a Chinese patient with Wilson's disease: a case report.
AB  - BACKGROUND: Wilson's disease (WD) is an autosomal recessive disorder
      characterized by copper accumulation. ATP7B gene mutations lead to ATP7B protein
      dysfunction, which in turn causes Wilson's disease. CASE PRESENTATION: We
      describe a male case of Wilson's disease diagnosed at 10 years after routine
      biochemical test that showed low serum ceruloplasmin levels and Kayser-Fleischer
      rings in both corneas. Analysis of the ATP7B gene revealed compound heterozygous
      mutations in the proband, including the reported c.3517G > A mutation and a novel
      c.532_574del mutation. The c.532_574del mutation covered a 43-bp region in exon
      2, and resulted in a frameshift mutation (p.Leu178PhefsX10). By base sequence
      analysis, two microhomologies (TCTCA) were observed on both deletion breakpoints
      in the ATP7B gene. Meanwhile, the presence of some sequence motifs associated
      with DNA breakage near the deletion region promoted DNA strand break.
      CONCLUSIONS: By comparison, a replication-based mechanism named fork stalling and
      template switching/ microhomology-mediated break-induced replication
      (FoSTeS/MMBIR) was used to explain the formation of this novel deletion mutation.

PMID- 29649981
TI  - In silico cancer research towards 3R.
AB  - BACKGROUND: Improving our understanding of cancer and other complex diseases
      requires integrating diverse data sets and algorithms. Intertwining in vivo and
      in vitro data and in silico models are paramount to overcome intrinsic
      difficulties given by data complexity. Importantly, this approach also helps to
      uncover underlying molecular mechanisms. Over the years, research has introduced
      multiple biochemical and computational methods to study the disease, many of
      which require animal experiments. However, modeling systems and the comparison of
      cellular processes in both eukaryotes and prokaryotes help to understand specific
      aspects of uncontrolled cell growth, eventually leading to improved planning of
      future experiments. According to the principles for humane techniques milestones
      in alternative animal testing involve in vitro methods such as cell-based models
      and microfluidic chips, as well as clinical tests of microdosing and imaging. Up
      to-date, the range of alternative methods has expanded towards computational
      approaches, based on the use of information from past in vitro and in vivo
      experiments. In fact, in silico techniques are often underrated but can be vital
      to understanding fundamental processes in cancer. They can rival accuracy of
      biological assays, and they can provide essential focus and direction to reduce
      experimental cost. MAIN BODY: We give an overview on in vivo, in vitro and in
      silico methods used in cancer research. Common models as cell-lines, xenografts,
      or genetically modified rodents reflect relevant pathological processes to a
      different degree, but can not replicate the full spectrum of human disease. There
      is an increasing importance of computational biology, advancing from the task of
      assisting biological analysis with network biology approaches as the basis for
      understanding a cell's functional organization up to model building for
      predictive systems. CONCLUSION: Underlining and extending the in silico approach
      with respect to the 3Rs for replacement, reduction and refinement will lead
      cancer research towards efficient and effective precision medicine. Therefore, we
      suggest refined translational models and testing methods based on integrative
      analyses and the incorporation of computational biology within cancer research.

PMID- 29649983
TI  - NCX-DB: a unified resource for integrative analysis of the sodium calcium
      exchanger super-family.
AB  - Na+/Ca2+ exchangers are low-affinity high-capacity transporters that mediate Ca2+
      extrusion by coupling Ca2+ efflux to the influx of Na+ ions. The Na+/Ca2+
      exchangers form a super-family comprised of three branches each differing in ion
      substrate selectivity: Na+/Ca2+ exchangers (NCX), Na+/Ca2+/K+ exchangers, and
      Ca2+/cation exchangers. Their primary function is to maintain Ca2+ homeostasis
      and play a particularly important role in excitable cells that experience
      transient Ca2+ fluxes. Research into the role and activity of Na+/Ca2+ exchangers
      has focused extensively on the cardio-vascular system, however, growing evidence
      suggests that Na+/Ca2+ exchangers play a key role in neuronal processes such as
      memory formation, learning, oligodendrocyte differentiation, neuroprotection
      during brain ischemia and axon guidance. They have also been implicated in
      pathologies such as Alzheimer's disease, Parkinson's disease, Multiple Sclerosis
      and Epilepsy, however, a clear understanding of their mechanism during disease is
      lacking. To date, there has never been a central resource or database for
      Na+/Ca2+ exchangers. With clear disease relevance and ever-increasing research on
      Na+/Ca2+ exchangers from both model and non-model species, a database that
      unifies the data on Na+/Ca2+ exchangers is needed for future research. NCX-DB is
      a publicly available database with a web interface that enables users to explore
      various Na+/Ca2+ exchangers, perform cross-species sequence comparison, identify
      new exchangers, and stay-up to date with recent literature. NCX-DB is available
      on the web via an interactive user interface with an intuitive design, which is
      applicable for the identification and comparison of Na+/Ca2+ exchanger proteins
      across diverse species.

PMID- 29649984
TI  - BB-Cl-Amidine as a novel therapeutic for canine and feline mammary cancer via
      activation of the endoplasmic reticulum stress pathway.
AB  - BACKGROUND: Mammary cancer is highly prevalent in dogs and cats and results in a
      poor prognosis due to critically lacking viable treatment options. Recent human
      and mouse studies have suggested that inhibiting peptidyl arginine deiminase
      enzymes (PAD) may be a novel breast cancer therapy. Based on the similarities
      between human breast cancer and mammary cancer in dogs and cats, we hypothesized
      that PAD inhibitors would also be an effective treatment for mammary cancer in
      these animals. METHODS: Canine and feline mammary cancer cell lines were treated
      with BB-Cl-Amidine (BB-CLA) and evaluated for viability and tumorigenicity.
      Endoplasmic reticulum stress was tested by western blot, immunofluorescence, and
      quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Canine
      and feline mammary cancer xenograft models were created using NOD scid gamma
      (NSG) mice, and were treated with BB-CLA for two weeks. RESULTS: We found that BB
      CLA reduced viability and tumorigenicity of canine and feline mammary cancer cell
      lines in vitro. Additionally, we demonstrated that BB-CLA activates the
      endoplasmic reticulum stress pathway in these cells by downregulating 78 kDa
      Glucose-regulated Protein (GRP78), a potential target in breast cancer for
      molecular therapy, and upregulating the downstream target gene DNA Damage
      Inducible Transcript 3 (DDIT3). Finally, we established a mouse xenograft model
      of both canine and feline mammary cancer in which we preliminarily tested the
      effects of BB-CLA in vivo. CONCLUSION: We propose that our established mouse
      xenograft models will be useful for the study of mammary cancer in dogs and cats,
      and furthermore, that BB-CLA has potential as a novel therapeutic for mammary
      cancer in these species.

PMID- 29649986
TI  - Correction to: Clinical evaluation of two different protein content formulas fed
      to full-term healthy infants: a randomized controlled trial.
AB  - Following the publication of the original article [1], it was brought to our
      attention that the authors' names and surnames were erroneously interchanged.

PMID- 29649985
TI  - The incidence of acute oxaliplatin-induced neuropathy and its impact on treatment
      in the first cycle: a systematic review.
AB  - BACKGROUND: Although acute oxaliplatin-induced neuropathy (OXIPN) is frequently
      regarded to be transient, recent studies have reported prolongation of infusion
      times, dose reduction and treatment cessation following the first dose of
      oxaliplatin in quarter of patients. Acute OXIPN is also a well-established risk
      factor for chronic neuropathy. However, there is underreporting of these
      parameters during the acute phase (<= 14 days). This paper systematically reviews
      the incidence of acute OXIPN and its impact on treatment in the first cycle.
      METHODS: A systematic literature search was performed using PubMed and Medline.
      Published original articles were included if they described details about
      prevalence of oxaliplatin-induced acute neuropathy. RESULTS: Fourteen studies,
      comprised of 6211 patients were evaluated. The majority of patients were treated
      with oxaliplatin in combination with leucovorin and fluorouracil (FOLFOX). Most
      studies used the National Cancer Institute Common Toxicity Criteria to assess
      acute neuropathy. Acute neuropathy (Grades 1-4) was the most common event with
      prevalence ranging from 4-98%, followed by haematological (1.4-81%) and
      gastrointestinal (1.2-67%) toxicities, respectively. Drug regimens, starting dose
      of oxaliplatin and neuropathy assessment tools varied across studies. In
      addition, moderate to severe toxicities were common in patients that received a
      large dose of oxaliplatin (> 85 mg/m2) and/ or combined drugs. The majority of
      studies did not report the factors affecting acute neuropathy namely the range
      (minimal) doses required to evoke acute neuropathy, patient and clinical risk
      factors. In addition, there was no systematic reporting of the number of patients
      subjected to prolonged infusion, dose reduction, treatment delay and treatment
      cessation during the acute phase. CONCLUSION: Despite the heterogeneity of
      studies regarding oxaliplatin starting dose, drug regimen, neuropathy assessment
      tools and study design, a large number of patients developed acute neuropathy. To
      develop a better preventive and therapeutic guideline for acute/chronic
      neuropathy, a prospective study should be conducted in a large cohort of patients
      in relation to drug regimen, starting/ranges (minimal) of doses producing acute
      neuropathy, treatment compliance, patient and clinical risk factors using a
      standardised neuropathy assessment tool.

PMID- 29649987
TI  - Multimodal imaging of foveoschisis and macular pseudohole associated with gyrate
      atrophy: a family report.
AB  - BACKGROUND: To report the results of multimodal imaging of a biochemically
      confirmed case of a family with gyrate atrophy (GA) associated with foveoschisis
      and macular pseudohole. CASE PRESENTATION: Two sisters presented to us with
      progressive bilateral decreased vision. The 26-year old sister had a best
      corrected visual acuity (BCVA) of 20/32 in the right eye (RE) and 20/100 in the
      left eye (LE). Dilated fundus examination revealed multiple bilateral
      chorioretinal atrophy areas in the midperipheral and peripheral retina.
      Fluorescein angiography did not show any leak in the macular area. Swept-source
      optical coherence tomography (SS-OCT) showed increased central macular thickness
      in both eyes with foveoschisis. Optical coherence tomography angiography (OCTA)
      showed petaloid non-reflective areas and some perifoveal microvascular
      alterations similar to telangiectasias in the deep capillary complex. The 30-year
      old sister had a BCVA of 20/20 in the RE and 20/32 in the LE. SS-OCT was normal
      in the RE and demonstrated a macular pseudohole with a fine epiretinal membrane
      in the LE. The persistent retinal tissue at the base of the pseudohole was
      disorganised. Blood tests showed hyperornithinemia in the 2 cases. Based on these
      observations, the patients were diagnosed with gyrate atrophy of the choroid and
      retina and were treated with a pyridoxine supplement and an arginine-restricted
      diet. CONCLUSIONS: Foveoschisis and macular pseudohole may be associated in GA,
      increasing the risk of rapid vision loss. OCTA is an interesting imaging tool
      that can help to better understand the pathophysiological mechanism of these
      macular involvements in GA.

PMID- 29649988
TI  - The function and morphology of Meibomian glands in patients with thyroid eye
      disease: a preliminary study.
AB  - BACKGROUND: To investigate function and morphology of the meibomian gland (MG) in
      patients with thyroid eye disease (TED). METHODS: In this prospective case series
      study, patients with unilateral or bilateral TED were consecutively enrolled. The
      diagnosis of TED was based on the typical orbital findings and/or radiographic
      evidence. The disease activity of TED was classified according to the clinical
      activity score (CAS). Degrees of lagophthalmos and exophthalmos, blinking rates,
      and results of the Schirmer test 1 were also recorded. All patients completed the
      SPEED questionnaire and underwent MG assessment, including lipid layer thickness
      (LLT), MG dropout (MGd), and MG expression. RESULTS: In total 31 eyes from 17
      patients with unilateral or bilateral TED were included. Patients were divided
      into inactive TED (CAS 0-1; 20 eyes from 11 patients) and active TED (CAS 2-3, 11
      eyes from 6 patients) groups. MGd was significantly more severe in the active TED
      than the inactive TED group [Median (Inter-quartile region): 3.0 (2.0-3.0) vs.
      2.0 (1.0-2.0) degree, P = 0.04]. However, patients with active TED had thicker
      LLT than those with inactive TED (90.0 [80.0-100.0] vs. 65.0 [47.8-82.5] nm, P =
      0.02), and LLT was positively correlated with lagophthalmos (r = 0.37, P = 0.04).
      CONCLUSIONS: Patients with active TED had more severe MGd, but thicker LLT.
      Active TED may cause periglandular inflammation of MGs, leading to MGd, but
      compensatory secretion from residual MGs and lagophthalmos-induced forceful
      blinking might temporarily release more lipids over the tear film.

PMID- 29649989
TI  - Evaluation of efficacy and safety for Brucea javanica oil emulsion in the control
      of the malignant pleural effusions via thoracic perfusion.
AB  - BACKGROUND: Brucea javanica oil emulsion (BJOE) is traditional Chinese medicine
      with implicated anti-tumor activity, which has been used for treating lung cancer
      in China. The aim of this investigation was to evaluate the effects and safety of
      intrapleural injection of BJOE in treating malignant pleural effusion (MPE).
      METHODS: The randomised controlled trials (RCTs) on the effects and safety of
      BJOE in treating MPE were searched from electronic medical database including
      MEDLINE, SCI, EMBASE, Cochrance Library and CNKI. A total of 14 RCTs with 1085
      patients were involved in this meta-analysis. RESULTS: The overall response rate
      (ORR) of traditional chemotherapy drugs plus BJOE was higher than that of
      traditional chemotherapy drugs alone (p = 0.001; odds ratio = 1.39). Meanwhile,
      the combination of BJOE and traditional chemotherapy drugs improved the quality
      of life (QOL) of patients with MPE (p < 0.001; odds ratio = 1.56) compared with
      traditional chemotherapy drugs alone. Moreover, the participation of BJOE reduced
      the myelotoxicity and digestive reactions caused by traditional chemotherapy
      drugs (p < 0.05). CONCLUSIONS: The efficacy and safety of traditional
      chemotherapy drugs plus BJOE was superior to traditional chemotherapy drugs alone
      via intrapleural injection in controlling MPE, which suggested that BJOE can be
      used to treat MPE.

PMID- 29649990
TI  - Correction to: Genomics of NSCLC patients both affirm PD-L1 expression and
      predict their clinical responses to anti-PD-1 immunotherapy.
AB  - It has been highlighted that in the original manuscript [1] Table S3 'An example
      of the predictive computational modeling process. Specific details on an annexure
      section of the PD-L1 pathway show the step-by-step reactions, mechanisms, and
      reaction equations that occur. Such reactions also occurred in all of the other
      pathways' was omitted and did not appear in the Additional files and that the
      Additional files were miss-numbered thereafter. This Correction shows the correct
      and incorrect Additional files. The original article has been updated.

PMID- 29649991
TI  - Interpersonal communication regarding pregnancy-related services: friends versus
      health professionals as conduits for information.
AB  - BACKGROUND: Social network characteristics influence a wide range of health
      behaviors but few studies examine the relationship between social network
      characteristics and pregnancy-related outcomes. METHODS: Using a baseline survey
      from a behavior change pilot project in the Upper West region of Ghana, we
      examine four outcomes: (1) early antenatal care, (2) having at least four
      antenatal care visits, (3) skilled birth attendance, and (4) postpartum care. We
      collected demographic and network data from 1606 women of reproductive age who
      had a child in the five years preceding the survey. We estimated associations by
      regressing the four pregnancy-related outcomes on the demographic and network
      characteristics. RESULTS: The results suggest that there is little interpersonal
      communication about pregnancy-related issues, as 60.2% of respondents reported
      talking to no one. For those women who did talk to someone, communication with a
      health professional had the strongest association with accessing services (e.g.,
      Adjusted Odds Ratio [AOR] = 8.02, p < 0.01, for having a facility birth).
      Communicating with friends was also significantly associated with outcomes (AOR =
      4.23, p < 0.0, for having a facility birth). CONCLUSIONS: This study provides
      evidence that there was little social communication about pregnancy-related
      issues in these communities at that time, indicating that an intervention to
      promote such communication could be successful. In addition, women who reported
      discussing pregnancy-related issues with friends or a health professional were
      more likely to access a birth facility and have a skilled birth attendant than
      those who reported discussing the same topics with their partner.

PMID- 29649992
TI  - Protocol for promoting recovery optimization of walking activity in stroke
      (PROWALKS): a randomized controlled trial.
AB  - BACKGROUND: Stroke survivors are more physically inactive than even the most
      sedentary older adults, and low activity is associated with increased risk of
      recurrent stroke, medical complications, and mortality. We hypothesize that the
      combination of a fast walking intervention that improves walking capacity, with a
      step activity monitoring program that facilitates translation of gains from the
      clinic to the "real-world", would generate greater improvements in real world
      walking activity than with either intervention alone. METHODS: Using a single
      blind randomized controlled experimental design, 225 chronic (> 6 months) stroke
      survivors complete 12 weeks of fast walking training, a step activity monitoring
      program or a fast walking training + step activity monitoring program. Main
      eligibility criteria include: chronic ischemic or hemorrhagic stroke (> 6 months
      post), no evidence of cerebellar stroke, baseline walking speed between 0.3 m/s
      and 1.0 m/s, and baseline average steps / day < 8000. The primary (steps per
      day), secondary (self-selected and fastest walking speed, walking endurance,
      oxygen consumption) and exploratory (vascular events, blood lipids, glucose,
      blood pressure) outcomes are assessed prior to initiating treatment, after the
      last treatment and at a 6 and 12-month follow-up. Moderation of the changes in
      outcomes by baseline characteristics are evaluated to determine for whom the
      interventions are effective. DISCUSSION: Following completion of this study, we
      will not only understand the efficacy of the interventions and the individuals
      for which they are effective, we will have the necessary information to design a
      study investigating the secondary prevention benefits of improved physical
      activity post-stroke. This study is, therefore, an important step in the
      development of both rehabilitative and secondary prevention guidelines for
      persons with stroke. TRIAL REGISTRATION: ClinicalTrials.gov Identifier:
      NCT02835313 . First Posted: July 18, 2016.

PMID- 29649993
TI  - VIPER: Visualization Pipeline for RNA-seq, a Snakemake workflow for efficient and
      complete RNA-seq analysis.
AB  - BACKGROUND: RNA sequencing has become a ubiquitous technology used throughout
      life sciences as an effective method of measuring RNA abundance quantitatively in
      tissues and cells. The increase in use of RNA-seq technology has led to the
      continuous development of new tools for every step of analysis from alignment to
      downstream pathway analysis. However, effectively using these analysis tools in a
      scalable and reproducible way can be challenging, especially for non-experts.
      RESULTS: Using the workflow management system Snakemake we have developed a user
      friendly, fast, efficient, and comprehensive pipeline for RNA-seq analysis. VIPER
      (Visualization Pipeline for RNA-seq analysis) is an analysis workflow that
      combines some of the most popular tools to take RNA-seq analysis from raw
      sequencing data, through alignment and quality control, into downstream
      differential expression and pathway analysis. VIPER has been created in a modular
      fashion to allow for the rapid incorporation of new tools to expand the
      capabilities. This capacity has already been exploited to include very recently
      developed tools that explore immune infiltrate and T-cell CDR (Complementarity
      Determining Regions) reconstruction abilities. The pipeline has been conveniently
      packaged such that minimal computational skills are required to download and
      install the dozens of software packages that VIPER uses. CONCLUSIONS: VIPER is a
      comprehensive solution that performs most standard RNA-seq analyses quickly and
      effectively with a built-in capacity for customization and expansion.

PMID- 29649994
TI  - Bile acids at neutral and acidic pH induce apoptosis and gene cleavages in
      nasopharyngeal epithelial cells: implications in chromosome rearrangement.
AB  - BACKGROUND: Chronic rhinosinusitis (CRS) increases the risk of developing
      nasopharyngeal carcinoma (NPC) while nasopharyngeal reflux is known to be one of
      the major aetiological factors of CRS. Bile acid (BA), the component of gastric
      duodenal contents, has been recognised as a carcinogen. BA-induced apoptosis was
      suggested to be involved in human malignancies. Cells have the potential and
      tendency to survive apoptosis. However, cells that evade apoptosis upon erroneous
      DNA repair may carry chromosome rearrangements. Apoptotic nuclease, caspase
      activated deoxyribonuclease (CAD) has been implicated in mediating translocation
      in leukaemia. We hypothesised that BA-induced apoptosis may cause chromosome
      breaks mediated by CAD leading to chromosome rearrangement in NPC. This study
      targeted the AF9 gene located at 9p22 because 9p22 is one of the most common
      deletion sites in NPC. METHODS: We tested the ability of BA at neutral and acidic
      pH in inducing phosphatidylserine (PS) externalisation, reactive oxygen species
      (ROS) production, mitochondrial membrane potential (MMP) disruption, and caspase
      3/7 activity in normal nasopharyngeal epithelial (NP69) and NPC (TWO4) cells.
      Inverse-PCR (IPCR) was employed to detect AF9 gene cleavages. To investigate the
      role of CAD in mediating these cleavages, caspase inhibition was performed. IPCR
      bands representing AF9 cleaved fragments were sequenced. RESULTS: BA-treated
      cells showed higher levels of PS externalisation, ROS production, MMP loss and
      caspase 3/7 activity than untreated control cells. The effect of BA in the
      induction of these intracellular events was enhanced by acid. BA at neutral and
      acidic pH also induced significant cleavage of the AF9 gene. These BA-induced
      gene cleavages were inhibited by Z-DEVD-FMK, a caspase-3 inhibitor. Intriguingly,
      a few chromosome breaks were identified within the AF9 region that was previously
      reported to participate in reciprocal translocation between the mixed lineage
      leukaemia (MLL) and AF9 genes in an acute lymphoblastic leukaemia (ALL) patient.
      CONCLUSIONS: These findings suggest a role for BA-induced apoptosis in mediating
      chromosome rearrangements in NPC. In addition, CAD may be a key player in
      chromosome cleavages mediated by BA-induced apoptosis. Persistent exposure of
      sinonasal tract to gastric duodenal refluxate may increase genomic instability in
      surviving cells.

PMID- 29649995
TI  - The prevalence and systemic risk factors of diabetic macular edema: a cross
      sectional study from Turkey.
AB  - BACKGROUND: The aim of this study was to evaluate the prevalence of diabetic
      macular edema (DME) utilizing optical coherence tomography (OCT), and to clarify
      the effects of the systemic findings and risk factors on the development of DME.
      METHODS: This cross-sectional study was conducted in the departments of
      ophthalmology and endocrinology at the Dokuz Eylul University School of Medicine
      in Izmir, Turkey. The demographics, type and duration of diabetes mellitus,
      treatment modality, smoking and alcohol consumption habits, as well as the
      systemic blood pressure, renal functional tests, hemoglobulin A1c level, serum
      lipid profile, and 24-h urine albumin level were noted and statistically
      analyzed. The relationships between the systemic findings and DME were studied.
      RESULTS: Four-hundred and thirteen eyes of 413 diabetic patients who were
      examined between January 2011 and July 2012 were enrolled in this study. The
      prevalence of DME was 15.3% among the patients. The males exhibited DME
      significantly more frequently than the females (p = 0.031), and the duration of
      diabetes was significantly longer in those patients with DME (p < 0.001). Those
      patients without DME frequently used antihyperlipidemic drugs and had a higher
      level of high density lipoprotein cholesterol (p = 0.040 and p = 0.046,
      respectively). The patient's alcohol consumption, nephropathy, neuropathy,
      previous cataract surgery, severity of diabetic retinopathy, and insulin usage
      were statistically significant factors with regard to the DME prevalence.
      CONCLUSIONS: This study demonstrated the prevalence of DME in Turkey by utilizing
      OCT. The development of DME can be avoided or limited and the response to
      treatment may be improved by the regulation of the DME risk factors.

PMID- 29649996
TI  - The effects of synbiotic supplementation on hormonal status, biomarkers of
      inflammation and oxidative stress in subjects with polycystic ovary syndrome: a
      randomized, double-blind, placebo-controlled trial.
AB  - BACKGROUND: To our knowledge, no reports are available indicating the effects of
      synbiotic supplementation on hormonal status, biomarkers of inflammation and
      oxidative stress in subjects with polycystic ovary syndrome (PCOS). This research
      was done to assess the effects of synbiotic supplementation on hormonal status,
      biomarkers of inflammation and oxidative stress in subjects with PCOS. METHODS:
      This randomized double-blind, placebo-controlled trial was conducted on 60
      subjects diagnosed with PCOS according to the Rotterdam criteria. Subjects were
      randomly assigned into two groups to take either synbiotic (n = 30) or placebo (n
      = 30) for 12 weeks. Endocrine, inflammation and oxidative stress biomarkers were
      quantified at baseline and after the 12-week intervention. RESULTS: After the 12
      week intervention, compared with the placebo, synbiotic supplementation
      significantly increased serum sex hormone-binding globulin (SHBG) (changes from
      baseline in synbiotic group: + 19.8 +/- 47.3 vs. in placebo group: + 0.5 +/- 5.4
      nmol/L, p = 0.01), plasma nitric oxide (NO) (changes from baseline in synbiotic
      group: + 5.5 +/- 4.8 vs. in placebo group: + 0.3 +/- 9.1 MUmol/L, p = 0.006), and
      decreased modified Ferriman Gallwey (mF-G) scores (changes from baseline in
      synbiotic group: - 1.3 +/- 2.5 vs. in placebo group: - 0.1 +/- 0.5, p = 0.01) and
      serum high-sensitivity C-reactive protein (hs-CRP) (changes from baseline in
      synbiotic group: - 950.0 +/- 2246.6 vs. in placebo group: + 335.3 +/- 2466.9
      ng/mL, p = 0.02). We did not observe any significant effect of synbiotic
      supplementation on other hormonal status and biomarkers of oxidative stress.
      CONCLUSIONS: Overall, synbiotic supplementation for 12 weeks in PCOS women had
      beneficial effects on SHBG, mFG scores, hs-CRP and NO levels, but did not affect
      other hormonal status and biomarkers of oxidative stress. TRIAL REGISTRATION:
      This study was retrospectively registered in the Iranian website ( www.irct.ir )
      for registration of clinical trials ( IRCT201509115623N53 ), on 2015-09-27.

PMID- 29649997
TI  - Year-round effects of a four-week randomized controlled trial using different
      types of feedback on employees' physical activity.
AB  - BACKGROUND: This follow-up study investigated the year-round effects of a four
      week randomized controlled trial using different types of feedback on employees'
      physical activity, including a need-supportive coach intervention. METHODS:
      Participants (n = 227) were randomly assigned to a Minimal Intervention Group
      (MIG; no feedback), a Pedometer Group (PG; feedback on daily steps only), a
      Display Group (DG; feedback on daily steps, on daily moderate-to-vigorous
      physical activity [MVPA] and on total energy expenditure [EE]), or a Coaching
      Group (CoachG; same as DG with need supportive coaching). Daily physical activity
      level (PAL; Metabolic Equivalent of Task [MET]), number of daily steps, daily
      minutes of moderate to vigorous physical activity (MVPA), active daily EE (EE > 3
      METs) and total daily EE were measured at five time points: before the start of
      the 4-week intervention, one week after the intervention, and 3, 6, and 12 months
      after the intervention. RESULTS: For minutes of MVPA, MIG showed higher mean
      change scores compared with the DG. For steps and daily minutes of MVPA,
      significantly lower mean change scores emerged for MIG compared with the PG.
      Participants of the CoachG showed significantly higher change scores in PAL,
      steps, minutes of MVPA, active EE, total EE compared with the MIG. As
      hypothesized, participants of the CoachG had significantly higher mean change
      scores in PAL and total EE compared with groups that only received feedback.
      However, no significant differences were found for steps, minutes of MVPA and
      active EE between CoachG and PG. CONCLUSIONS: Receiving additional need
      supportive coaching resulted in a higher PAL and active EE compared with
      measurement (display) feedback only. These findings suggest to combine feedback
      on physical activity with personal coaching in order to facilitate long-term
      behavioral change. When it comes to increasing steps, minutes of MVPA or active
      EE, a pedometer constitutes a sufficient tool. TRIAL REGISTRATION: Clinical
      Trails.gov NCT01432327 . Date registered: 12 September 2011.

PMID- 29649998
TI  - Effectiveness of ultrasonography and nerve conduction studies in the diagnosing
      of carpal tunnel syndrome: clinical trial on accuracy.
AB  - BACKGROUND: The aim of this study was to evaluate the effectiveness of two
      diagnostic tests routinely used for diagnosing carpal tunnel syndrome (CTS)
      ultrasonography (US) and nerve conduction studies (NCS)-by comparing their
      accuracy based on surgical results, with the remission of paresthesia as the
      reference standard. METHODS: We enrolled 115 patients, all of the female gender
      with a high probability of a clinical diagnosis of CTS. All patients underwent US
      and NCS for a diagnosis and subsequent surgical treatment. As a primary outcome,
      the accuracy of the US and NCS diagnoses was measured by comparing their
      diagnoses compared with those determined by the surgical outcomes. Their accuracy
      was secondarily evaluated based on before and after scores of the Boston Carpal
      Tunnel Questionnaire (BCTQ). RESULTS: Overall, 104 patients (90.4%) were
      diagnosed with CTS by the surgical reference standard, 97 (84.3%) by NCS, and 90
      (78.3%) by US. The concordance of NCS and surgical treatment (p < 0.001; kappa =
      0.648) was superior to that of US and surgical treatment (p < 0.001; kappa =
      0.423). The sensitivity and specificity of US and NCS were similar (p = 1.000 and
      p = 0.152, respectively: McNemar's test). The BCTQ scores were lower after
      surgery in patients diagnosed by both US and NCS (p < 0.001and p < 0.001,
      respectively: analysis of variance). CONCLUSIONS: US and NCS effectively
      diagnosed CTS with good sensitivity but were not effective enough to rule out a
      suspicion of CTS. TRIAL REGISTRATION: This study was registered at September, 10
      th, 2015, and the registration number was NCT02553811 .

PMID- 29649999
TI  - The financial transaction between counseling and nursing care service centers
      (CNCSCs) and their clients: a qualitative study.
AB  - BACKGROUND: Community-oriented nursing care is an important model of nursing
      care. Counseling and Nursing Care Service Centers (CNCSCs) have been providing
      these private services to the Iranian community for nearly two decades. Resource
      management, cost-benefit analysis and affordability are important steps in
      providing these services. The present study was conducted to explore the
      challenges of financial transactions between CNCSCs and their clients. METHODS:
      This study has a qualitative design and was conducted on a total of 30
      participants, consisting of CNCSC managers, staff, physicians and clients who
      were selected through purposive theoretical sampling. Data were collected through
      in-depth interviews and direct observations and were analyzed using conventional
      qualitative content analysis. RESULTS: The analysis of the data led to the
      extraction of three main categories, including the flaunted atmosphere due to
      direct financial transaction, instability in determining tariffs for nursing
      services and the use of strategies for cost-effective services and client
      satisfaction. CONCLUSION: To increase affordability and satisfaction and expand
      private community-based nursing. Services, appropriate financial policies should
      be designed and applied that can lead to transparent and simple financial
      transactions with the clients by way of indirect monetary exchanges. These
      policies should be designed in a systematic manner with integrity, facilitate
      inter-sectorial cooperation in the health sector and be cost-effective for the
      clients, insurance companies and the health system.

PMID- 29650000
TI  - Favorable outcome of patients with lung adenocarcinoma harboring POLE mutations
      and expressing high PD-L1.
AB  - Mutations in polymerase epsilon (POLE) confer favorable prognosis and outcomes in
      various cancer types, but their role in non-small cell lung cancer (NSCLC) is
      unknown. Utilizing the data of 513 patients with adenocarcinoma (LUAD) and 497
      patients with squamous cell carcinoma (LUSC) from The Cancer Genome Atlas (TCGA)
      cohort, we tested the prognostic value of POLE mutations and programmed cell
      death ligand 1 (PD-L1) expression in the two main subtypes of NSCLC. POLE
      mutation is a favorable biomarker for the improved overall survival (OS) of the
      LUSC patients (P = 0.033, 28 mutant vs. 469 wildtype patients), but not that of
      the LUAD patients (P = 0.12, 31 mutant vs. 482 wildtype patients). POLE-mutant
      LUAD patients with high expression of PD-L1 (Mut-High, n = 6) exhibited improved
      OS (P = 0.024) when compared to POLE-mutant patients with low PD-L1 expression
      (Mut-Low, n = 24) and other patients without POLE mutation (n = 476). This
      benefit was not due to the high content of the tumor infiltrating lymphocytes.
      Instead, the antitumor immune response was activated in Mut-High patients so that
      these patients were likely responding more effectively to immuno-oncology (IO)
      treatments; whereas genes involved with metabolic pathways were enriched in Mut
      Low group, which may cause the decreased OS of these patients. Our study sheds
      light on the molecular basis of NSCLC and adds to our understanding of responses
      to chemotherapy and IO therapy.

PMID- 29650001
TI  - Prediction of autonomic dysreflexia during urodynamics: a prospective cohort
      study.
AB  - BACKGROUND: Autonomic dysreflexia is a severe and potentially life-threatening
      condition in patients with spinal cord injury, as it can lead to myocardial
      ischemia, brain hemorrhage, or even death. Urodynamic investigation is the gold
      standard to assess neurogenic lower urinary tract dysfunction due to spinal cord
      injury and reveal crucial pathological findings, such as neurogenic detrusor
      overactivity. However, neurogenic detrusor overactivity and urodynamic
      investigation are known to be leading triggers of autonomic dysreflexia.
      Therefore, we aimed to determine predictors of autonomic dysreflexia in
      individuals with spinal cord injury during urodynamic investigation. METHODS:
      This prospective cohort study included 300 patients with spinal cord injuries and
      complete datasets of continuous non-invasive cardiovascular monitoring, recorded
      during same session repeat urodynamic investigation. We used logistic regression
      to reveal predictors of autonomic dysreflexia during urodynamic investigation.
      RESULTS: We found that level of injury and presence of neurogenic detrusor
      overactivity were the only two independent significant predictors for autonomic
      dysreflexia during urodynamic investigation. A lesion at spinal segment T6 or
      above (odds ratio (OR) 5.5, 95% CI 3.2-9.4) compared to one at T7 or below, and
      presence of neurogenic detrusor overactivity (OR 2.7, 95% confidence interval
      (CI) 1.4-4.9) were associated with a significant increased odds of autonomic
      dysreflexia during urodynamic investigation. Both odds persisted after adjustment
      for age, sex, and completeness and stage of injury (adjusted OR (AOR) 6.6, 95% CI
      3.8-11.7, and AOR 2.2, 95% CI 1.1-4.5, respectively). Further stratification by
      lesion level showed level-dependent significantly increased adjusted odds of
      autonomic dysreflexia, i.e., from C1-C4 (AOR 16.2, 95% CI 5.9-57.9) to T4-T6 (AOR
      2.6, 95% CI 1.3-5.2), compared to lesions at T7 or below. CONCLUSIONS: In
      patients with neurogenic lower urinary tract dysfunction due to spinal cord
      injury, autonomic dysreflexia is independently predicted by lesion level and
      presence of neurogenic detrusor overactivity. Considering the health risks
      associated with autonomic dysreflexia, such as seizures, stroke, retinal
      bleeding, or even death, we recommend both continuous cardiovascular monitoring
      during urodynamic investigation in all spinal cord-injured patients with emphasis
      on those with cervical lesions, and appropriate neurogenic detrusor overactivity
      treatment to reduce the probability of potentially life-threatening
      complications. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01293110 .

PMID- 29650002
TI  - Identifying bottlenecks in the iron and folic acid supply chain in Bihar, India:
      a mixed-methods study.
AB  - BACKGROUND: Maternal anaemia prevalence in Bihar, India remains high despite
      government mandated iron supplementation targeting pregnant women. Inadequate
      supply has been identified as a potential barrier to iron and folic acid (IFA)
      receipt. Our study objective was to examine the government health system's IFA
      supply and distribution system and identify bottlenecks contributing to
      insufficient IFA supply. METHODS: Primary data collection was conducted in
      November 2011 and July 2012 across 8 districts in Bihar, India. A cross
      sectional, observational, mixed methods approach was utilized. Auxiliary Nurse
      Midwives were surveyed on current IFA supply and practices. In-depth interviews
      (n = 59) were conducted with health workers at state, district, block, health sub
      centre, and village levels. RESULTS: Overall, 44% of Auxiliary Nurse Midwives
      were out of IFA stock. Stock levels and supply chain practices varied greatly
      across districts. Qualitative data revealed specific bottlenecks impacting IFA
      forecasting, procurement, storage, disposal, lack of personnel, and few training
      opportunities for key players in the supply chain. CONCLUSIONS: Inadequate IFA
      supply is a major constraint to the IFA supplementation program, the extent of
      which varies widely across districts. Improvements at all levels of
      infrastructure, practices, and effective monitoring will be critical to
      strengthen the IFA supply chain in Bihar.

PMID- 29650003
TI  - Judging a salmon by its spots: environmental variation is the primary determinant
      of spot patterns in Salmo salar.
AB  - BACKGROUND: In fish, morphological colour changes occur from variations in
      pigment concentrations and in the morphology, density, and distribution of
      chromatophores in the skin. However, the underlying mechanisms remain unresolved
      in most species. Here, we describe the first investigation into the genetic and
      environmental basis of spot pattern development in one of the world's most
      studied fishes, the Atlantic salmon. We reared 920 salmon from 64 families of
      domesticated, F1-hybrid and wild origin in two contrasting environments
      (Hatchery; tanks for the freshwater stage and sea cages for the marine stage, and
      River; a natural river for the freshwater stage and tanks for the marine stage).
      Fish were measured, photographed and spot patterns evaluated. RESULTS: In the
      Hatchery experiment, significant but modest differences in spot density were
      observed among domesticated, F1-hybrid (1.4-fold spottier than domesticated) and
      wild salmon (1.7-fold spottier than domesticated). A heritability of 6% was
      calculated for spot density, and a significant QTL on linkage group SSA014 was
      detected. In the River experiment, significant but modest differences in spot
      density were also observed among domesticated, F1-hybrid (1.2-fold spottier than
      domesticated) and wild salmon (1.8-fold spottier than domesticated). Domesticated
      salmon were sevenfold spottier in the Hatchery vs. River experiment. While
      different wild populations were used for the two experiments, on average, these
      were 6.2-fold spottier in the Hatchery vs. River experiment. Fish in the Hatchery
      experiment displayed scattered to random spot patterns while fish in the River
      experiment displayed clustered spot patterns. CONCLUSIONS: These data demonstrate
      that while genetics plays an underlying role, environmental variation represents
      the primary determinant of spot pattern development in Atlantic salmon.

PMID- 29650004
TI  - Comparing GPs' risk attitudes for their own health and for their patients' : a
      troubling discrepancy?
AB  - BACKGROUND: In this paper, we report the results of risk attitudes elicitation of
      a French general practitioners national representative sample (N=1568). METHODS:
      Willingness to take risks in four different domains (daily life, financial
      matters, own health and patient health) was collected through a large-scale
      telephone interview of GPs using self-reported 11-point Likert scale questions.
      RESULTS: We uncover some specificities of the GPs population regarding their
      attitudes towards risk. In particular, we detect an important positive gap
      between their willingness to take risks in the domain of their own health and in
      the domain of the heath of their patients. This "patient-regarding" risk aversion
      is discussed with respect to its important consequences regarding medical
      behavior bias. CONCLUSIONS: We confirm the self-other discrepancy found in the
      medical literature on physicians' behaviors and emphasize the utility of the
      study and measures of personality traits such as "risk attitudes" for the medical
      professions and for the population they address.

PMID- 29650005
TI  - The effect of case management and vector-control interventions on space-time
      patterns of malaria incidence in Uganda.
AB  - BACKGROUND: Electronic reporting of routine health facility data in Uganda began
      with the adoption of the District Health Information Software System version 2
      (DHIS2) in 2011. This has improved health facility reporting and overall data
      quality. In this study, the effects of case management with artemisinin-based
      combination therapy (ACT) and vector control interventions on space-time patterns
      of disease incidence were determined using DHIS2 data reported during 2013-2016.
      METHODS: Bayesian spatio-temporal negative binomial models were fitted on
      district-aggregated monthly malaria cases, reported by two age groups, defined by
      a cut-off age of 5 years. The effects of interventions were adjusted for socio
      economic and climatic factors. Spatial and temporal correlations were taken into
      account by assuming a conditional autoregressive and a first-order autoregressive
      AR(1) process on district and monthly specific random effects, respectively.
      Fourier trigonometric functions were incorporated in the models to take into
      account seasonal fluctuations in malaria transmission. RESULTS: The temporal
      variation in incidence was similar in both age groups and depicted a steady
      decline up to February 2014, followed by an increase from March 2015 onwards. The
      trends were characterized by a strong bi-annual seasonal pattern with two peaks
      during May-July and September-December. Average monthly incidence in children < 5
      years declined from 74.7 cases (95% CI 72.4-77.1) in 2013 to 49.4 (95% CI 42.9
      55.8) per 1000 in 2015 and followed by an increase in 2016 of up to 51.3 (95% CI
      42.9-55.8). In individuals >= 5 years, a decline in incidence from 2013 to 2015
      was followed by an increase in 2016. A 100% increase in insecticide-treated nets
      (ITN) coverage was associated with a decline in incidence by 44% (95% BCI 28
      59%). Similarly, a 100% increase in ACT coverage reduces incidence by 28% (95%
      BCI 11-45%) and 25% (95% BCI 20-28%) in children < 5 years and individuals >= 5
      years, respectively. The ITN effect was not statistically important in older
      individuals. The space-time patterns of malaria incidence in children < 5 are
      similar to those of parasitaemia risk predicted from the malaria indicator survey
      of 2014-15. CONCLUSION: The decline in malaria incidence highlights the
      effectiveness of vector-control interventions and case management with ACT in
      Uganda. This calls for optimizing and sustaining interventions to achieve
      universal coverage and curb reverses in malaria decline.

PMID- 29650006
TI  - Beclomethasone dipropionate and formoterol fumarate synergistically interact in
      hyperresponsive medium bronchi and small airways.
AB  - BACKGROUND: Corticosteroids increase the expression of beta2-adrenoceptors (beta2
      ARs) and protect them against down-regulation. Conversely, beta2-AR agonists
      improve the anti-inflammatory action of corticosteroids. Nevertheless, it is
      still uncertain whether adding a long-acting beta2-AR agonist (LABA) to an
      inhaled corticosteroid (ICS) results in an additive effect, or there is true
      synergy. Therefore, the aim of this study was to pharmacologically characterize
      the interaction between the ICS beclomethasone diproprionate (BDP) and the LABA
      formoterol fumarate (FF) in a validated human ex vivo model of bronchial asthma.
      METHODS: Human medium and small airways were stimulated by histamine and treated
      with different concentrations of BDP and FF, administered alone and in
      combination at concentration-ratio reproducing ex vivo that of the currently
      available fixed-dose combination (FDC; BDP/FF 100:6 combination-ratio).
      Experiments were performed in non-sensitized (NS) and passively sensitized (PS)
      airways. The pharmacological interaction was assessed by using Bliss Independence
      and Unified Theory equations. RESULTS: BDP/FF synergistically increased the
      overall bronchorelaxation in NS and PS airways (+ 15.15% +/- 4.02%; P < 0.05 vs.
      additive effect). At low-to-medium concentrations the synergistic interaction was
      greater in PS than in NS bronchioles (+ 16.68% +/- 3.02% and + 7.27% +/- 3.05%,
      respectively). In PS small airways a very strong synergistic interaction
      (Combination Index: 0.08; + 20.04% +/- 2.18% vs. additive effect) was detected
      for the total concentrations of BDP/FF combination corresponding to 10.6 ng/ml.
      CONCLUSION: BDP/FF combination synergistically relaxed human bronchi; the extent
      of such an interaction was very strong at low-to-medium concentrations in PS
      small airways. TRIAL REGISTRATION: Not applicable.

PMID- 29650007
TI  - Malaria incidence and prevalence during the first year of life in Nanoro, Burkina
      Faso: a birth-cohort study.
AB  - BACKGROUND: Infants are thought to be protected against malaria during the first
      months of life mainly due to passage of maternal antibodies. However, in high
      transmission settings, malaria in early infancy is not uncommon and
      susceptibility to the infections varies between individuals. This study aimed to
      determine malaria morbidity and infection during early childhood in rural Burkina
      Faso. METHODS: Malariometric indices were determined over 1-year follow-up in a
      birth cohort of 734 infants living in Nanoro health district. Clinical malaria
      episodes were determined by passive case detection at peripheral health centres
      while asymptomatic malaria infections were identified during  4 cross-sectional
      surveys at 3, 6, 9 and 12 months of age. Plasmodium falciparum infections were
      detected by rapid diagnostic test and/or light microscopy (LM) and quantitative
      PCR (qPCR). RESULTS: In total, 717 clinical episodes were diagnosed by qPCR over
      8335.18 person-months at risk. The overall malaria incidence was 1.03 per child
      year and increased from 0.27 per child-year at 0-3 months of age to 1.92 per
      child-year at 9-12 months of age. Some 59% of children experienced at least one
      clinical episode with a median survival time estimated at 9.9 months, while 20%
      of infants experienced the first episode before 6 months of age. The majority of
      the clinical episodes were attributable to microscopic parasitaemia (84.2%), and
      there was a positive correlation between parasite density and age (Spearman's rho
      = 0.30; P < 0.0001). Prevalence of asymptomatic infections was similar at 3, 6
      and 9 months of age (17.7-20.1%) and nearly 1.6 times higher at 12 months
      (31.3%). Importantly, gametocyte prevalence among the LM-positive study
      population was 6.7%, but increased to 10% among asymptomatic infections. In
      addition, 46% of asymptomatic infections were only detected by qPCR suggesting
      that infants below 1 year are a potential reservoir for sustaining malaria
      transmission. Both symptomatic and asymptomatic infections showed marked seasonal
      distribution with the highest transmission period (July to December) accounting
      for about 89 and 77% of those infections, respectively. CONCLUSIONS: These
      findings indicate high and marked age and seasonal-dependency of malaria
      infections and disease during the first year of life in Nanoro, calling for
      intensified efforts to control malaria in rural Burkina Faso.

PMID- 29650008
TI  - The challenge of maintaining microscopist capacity at basic levels for malaria
      elimination in Jiangsu Province, China.
AB  - BACKGROUND: Local malaria transmission has decreased rapidly since the National
      Malaria Elimination Action Plan was launched in China in 2010. However, imported
      malaria cases from Africa and Southeast Asia still occur in China due to overseas
      laborers. Diagnosis by microscopy is the gold standard for malaria and is used in
      most hospitals in China. However, the current capacity of microscopists to manage
      malaria cases in hospitals and public health facilities to meet the surveillance
      needs to eliminate and prevent the reintroduction of malaria is unknown. METHODS:
      Malaria diagnoses were assessed by comparing the percentage of first visit and
      confirmed malaria diagnoses at Centers for Disease Control and Prevention (CDCs)
      and hospitals. The basic personnel information for public health departments and
      hospitals at different levels was investigated. The skills of microscopists for
      blood smear preparation and slide interpretation were also examined at the county
      and township levels. RESULTS: Inaccurate rate with 13.49% and 7.32%,
      respectively, in 2013 and 2014, from 341 and 355 reported cases from sub
      provincial levels in Jiangsu province. Most of the 523 malaria cases reported in
      Nantong Prefecture from 2000 to 2014 involved patients who first visited county
      CDCs seeking treatment, however, none of these cases received confirmed diagnosis
      of malaria in townships or villages.The staff at county CDCs and hospitals with a
      higher education background performed better at making and interpreting blood
      smears than staff from townships. CONCLUSIONS: The network for malaria
      elimination in an entire province has been well established. However, an
      insufficient capacity for malaria diagnosis was observed, especially the
      preparing and reading the blood smears at the township and village levels, which
      is a challenge to achieving and maintaining malaria elimination.

PMID- 29650009
TI  - Does precautionary information about electromagnetic fields trigger nocebo
      responses? An experimental risk communication study.
AB  - BACKGROUND: Regarding electromagnetic fields from mobile communication
      technologies, empirical studies have shown that precautionary information given
      to lay recipients increases their risk perceptions, i.e. the belief that
      electromagnetic fields are dangerous. Taking this finding one step further, the
      current study investigates whether precautionary information also leads to higher
      symptom perceptions in an alleged exposure situation. Building on existing
      research on nocebo responses to sham electromagnetic fields, an interaction of
      the precautionary information with personality characteristics was hypothesised.
      METHODS: An experimental design with sham exposure to an electromagnetic field of
      a WLAN device was deployed. The final sample is constituted by N = 137
      participants. Participants received either only basic information about the
      safety of current WLAN exposure limits or in addition also precautionary
      information (e.g. 'prefer wired connections if wireless technology can be
      relinquished'). Subsequently, symptoms and other variables were assessed before
      and after sham exposure to a WLAN electromagnetic field. RESULTS: Results are not
      in favour of the hypothesised effects. There was neither a main effect of
      precautionary information, nor were there any of the hypothesised interaction
      effects of precautionary information and personality characteristics on perceived
      symptoms under sham exposure. Exploratory analyses highlight the role of prior
      risk perception as a predictor of nocebo responses, and of symptom expectations
      as a mediator between these two variables. CONCLUSIONS: As the statistical power
      to detect even small effects was relatively high, we interpret this as a robust
      indication that precautionary information does not lead to increased nocebo
      responses by itself. The implications for health authorities' communication with
      the public are discussed.

PMID- 29650010
TI  - How timely closure can reduce outbreak duration: gastroenteritis in care homes in
      North West England, 2012-2016.
AB  - BACKGROUND: Data on outbreaks of infectious gastroenteritis in care homes have
      been collected using an internet-based surveillance system in North West England
      since 2012. We analysed the burden and characteristics of care home outbreaks to
      inform future public health decision-making. METHODS: We described
      characteristics of care homes and summary measures of the outbreaks such as
      attack rate, duration and pathogen identified. The primary analysis outcome was
      duration of closure following an outbreak. We used negative binomial regression
      to estimate Incidence Rate Ratios (IRR) and confidence intervals (CI) for each
      explanatory variable. RESULTS: We recorded 795 outbreaks from 379 care homes
      (37.1 outbreaks per 100 care homes per year). In total 11,568 cases, 75
      hospitalisations and 29 deaths were reported. Closure within three days of the
      first case (IRR = 0.442, 95%CI 0.366-0.534) was significantly associated with
      reduced duration of closure. The total size of the home (IRR = 1.426, 95%CI =
      1.275-1.595) and the total attack rate (IRR = 1.434, 95%CI = 1.257-1.595) were
      significantly associated with increased duration of closure. CONCLUSIONS: Care
      homes that closed promptly had outbreaks of shorter duration. Care home
      providers, and those advising them on infection control, should aim to close
      homes quickly to prevent lengthy disruption to services.

PMID- 29650011
TI  - Physical activity and chronic diseases among older people in a mid-size city in
      China: a longitudinal investigation of bipolar effects.
AB  - BACKGROUND: While previous studies have shown that regular physical activity can
      delay the onset of certain chronic diseases; less is known about the changes in
      physical activity practices following chronic disease diagnoses. China is
      experiencing a rapid aging transition, with physical activity an important
      routine in many older people's lives. This study utilizes the Health Belief Model
      to better understand the bidirectional relationships and bipolar effects between
      physical activity and chronic disease burden in Huainan City, a mid-sized city in
      China. METHODS: Longitudinal health survey data (2010-2015) from annual clinic
      visits for 3198 older people were obtained from a local hospital, representing
      97% of the older population in three contiguous neighborhoods in Huainan City.
      The chronic diseases studied included obesity, hypertension, diabetes,
      hyperlipidemia, cardiovascular diseases, liver and biliary system diseases, and
      poor kidney function. Multilevel logistic regression was used to examine
      differences in physical activity levels across socio-demographic groups. Cox
      proportional hazards models were used to examine the impacts of physical activity
      practice levels on chronic disease onsets. Logistic regression was used to
      estimate the effects of chronic disease diagnosis on physical activity practice
      levels. RESULTS: The prevalence of chronic diseases increased with increasing
      age, among men, and those with a lower education. Older people who were
      physically active experienced a later onset of chronic disease compared to their
      sedentary counterparts, particularly for obesity and diabetes. Following
      diagnosis of a chronic disease, physically active older people were more likely
      to increase their physical activity levels, while sedentary older people were
      less likely to initiate physical activity, demonstrating bipolar health
      trajectory effects. CONCLUSIONS: Health disparities among older people may widen
      as the sedentary experience earlier onsets of chronic diseases and worse health
      trajectories, compared to physically active people. Future health education
      communication and programmatic interventions should focus on sedentary and less
      healthy older populations to encourage healthy aging. These lessons from China
      may be applied to other countries also experiencing an increasing aging
      population.

PMID- 29650013
TI  - Life expectancy inequalities in the elderly by socioeconomic status: evidence
      from Italy.
AB  - BACKGROUND: Life expectancy considerably increased in most developed countries
      during the twentieth century. However, the increase in longevity is neither
      uniform nor random across individuals belonging to various socioeconomic groups.
      From an economic policy perspective, the difference in mortality by socioeconomic
      conditions challenges the fairness of the social security systems. We focus on
      the case of Italy and aim at measuring differences in longevity at older ages by
      individuals belonging to different socioeconomic groups, also in order to assess
      the effective fairness of the Italian public pension system, which is based on a
      notional defined contribution (NDC) benefit computation formula, whose rules do
      not take into account individual heterogeneity in expected longevity. METHODS: We
      use a longitudinal dataset that matches survey data on individual features
      recorded in the Italian module of the EU-SILC, with information on the whole
      working life and until death collected in the administrative archives managed by
      the Italian National Social Security Institute. In more detail, we follow until
      2009 a sample of 11,281 individuals aged at least 60 in 2005. We use survival
      analysis and measure the influence of a number of events experienced in the labor
      market and individual characteristics on mortality. Furthermore, through Kaplan
      Meier simulations of hypothetical social groups, adjusted by a Brass relational
      model, we estimate and compare differences in life expectancy of individuals
      belonging to different socioeconomic groups. RESULTS: Our findings confirm that
      socioeconomic status strongly predicts life expectancy even in old age. All
      estimated models show that the prevalent type of working activity before
      retirement is significantly associated with the risk of death, even when
      controlling for dozens of variables as proxies of individual demographic and
      socioeconomic characteristics. The risk of death for self-employed individuals is
      26% lower than that of employees, and life expectancy at 60 differs by five years
      between individuals with opposite socioeconomic statuses. CONCLUSIONS: Our study
      is the first that links results based on a micro survival analysis on subgroups
      of the elderly population with results related to the entire Italian population.
      The extreme differences in mortality risks by socioeconomic status found in our
      study confirm the existence of large health inequalities and strongly question
      the fairness of the Italian public pension system.

PMID- 29650012
TI  - Technologies to monitor the health of loaded skin tissues.
AB  - There are many situations where the skin and underlying soft tissues are
      compromised by mechanical loading in the form or pressure, or pressure in
      combination with shear. If sustained, this can lead to damage in the tissues
      particularly adjacent to bony prominences, resulting in chronic wounds. An array
      of bioengineering technologies have been adopted to assess the integrity of
      loaded soft tissues. This paper aims to review these approaches for the
      quantification, simulation and early detection of mechanically-induced skin
      damage. The review considers different measurements at the interface between the
      skin and support surface/medical device, involving pressure, shear, friction and
      the local microclimate. The potential of the techniques to monitor the
      physiological response of the skin to these external stimuli including
      biophysical measurement devices and sampling of biofluids are critically
      analysed. In addition, it includes an analysis of medical imaging technologies
      and computational modelling to provide a means by which tissue deformation can be
      quantified and thresholds for tissue damage defined. Bioengineering measurement
      and imaging technologies have provided an insight into the temporal status of
      loaded skin. Despite the advances in technology, to date, the translation to
      clinical tools which are robust and cost effective has been limited. There is a
      need to adapt existing technologies and simulation platforms to enable patients,
      carers and clinicians to employ appropriate intervention strategies to minimise
      soft tissue damage.

PMID- 29650014
TI  - Correlation analysis between the magnetic resonance imaging characteristics of
      osteoporotic vertebral compression fractures and the efficacy of percutaneous
      vertebroplasty: a prospective cohort study.
AB  - BACKGROUND: To explore the relationship between the magnetic resonance imaging
      (MRI) characteristics of osteoporotic vertebral compression fractures (OVCFs) and
      the efficacy of percutaneous vertebroplasty (PVP). METHODS: A prospective study
      was conducted to analyze the clinical and imaging data of 93 patients with OVCFs
      treated via PVP. A visual analogue scale (VAS), the Oswestry Disability Index
      (ODI), and the Medical Outcomes Study(MOS) 36-Item short-form health survey (SF
      36) were completed before surgery as well as 1 day and 1, 6, and 12 months after
      surgery. In addition, postoperative complications were recorded. According to the
      degree and ranges of bone marrow edema on MRI, the patients were divided into
      three groups: the mild (group A), moderate (group B), and severe (group C) bone
      marrow edema groups. Pain and dysfunction scores were compared across the three
      groups of patients before surgery as well as 1 day and 1, 6, and 12 months after
      surgery. RESULTS: The VAS, ODI, and SF-36 scores showed significant differences
      (P < 0.05) before and after surgery among the three groups. The ODI and SF-36
      scores were significantly different (P < 0.05) at 1 day and 1 month after surgery
      among the three groups. Groups A and B showed significantly better pain relief
      than group C. Group B experienced better pain relief than group A. These results
      indicate that PVP was associated with better pain relief effects among patients
      with a greater extent of bone marrow edema. The edema ranges of the vertebral
      fractures were negatively correlated with the postoperative VAS and ODI scores 1
      month after surgery, whereas the ranges were positively correlated with
      postoperative SF-36 scores 1 month after surgery. CONCLUSIONS: PVP is an
      effective treatment for OVCFs. Better outcomes were observed among patients with
      severe or moderate bone marrow edema rather than those with mild bone marrow
      edema. A greater degree of pain relief after PVP was correlated with faster
      recovery of the postoperative function. However, this correlation gradually
      became weak over time and disappeared 6 months after surgery. Therefore, PVP
      should be an option for early stage OVCFs, especially among patients with bone
      marrow edema signs on MRI.

PMID- 29650015
TI  - Inclusion and exclusion criteria used in non-specific low back pain trials: a
      review of randomised controlled trials published between 2006 and 2012.
AB  - BACKGROUND: Low back pain is a common health complaint resulting in substantial
      economic burden. Each year, upwards of 20 randomised controlled trials (RCTs)
      evaluating interventions for non-specific low back pain are published. Use of the
      term non-specific low back pain has been criticised on the grounds of encouraging
      heterogeneity and hampering interpretation of findings due to possible
      heterogeneous causes, challenging meta-analyses. We explored selection criteria
      used in trials of treatments for nsLBP. METHODS: A systematic review of English
      language reports of RCTs in nsLBP population samples, published between 2006 and
      2012, identified from MEDLINE, EMBASE, and the Cochrane Library databases, using
      a mixed-methods approach to analysis. Study inclusion and exclusion criteria were
      extracted, thematically categorised, and then descriptive statistics were used to
      summarise the prevalence by emerging category. RESULTS: We included 168 studies.
      Two inclusion themes (anatomical area, and symptoms and signs) were identified.
      Anatomical area was most reported as between costal margins and gluteal folds (n
      = 8, 5%), while low back pain (n = 150, 89%) with or without referred leg pain (n
      = 27, 16%) was the most reported symptom. Exclusion criteria comprised 21 themes.
      Previous or scheduled surgery (n = 84, 50%), pregnancy (n = 81, 48%), malignancy
      (n = 78, 46%), trauma (n = 63, 37%) and psychological conditions (n = 58, 34%)
      were the most common. Sub-themes of exclusion criteria mostly related to
      neurological signs and symptoms: nerve root compromise (n = 44, 26%),
      neurological signs (n = 34, 20%) or disc herniation (n = 30, 18%). Specific
      conditions that were most often exclusion criteria were spondylolisthesis (n =
      35, 21%), spinal stenosis (n = 31, 18%) or osteoporosis (n = 27, 16%).
      CONCLUSION: RCTs of interventions for non-specific low back pain have
      incorporated diverse inclusion and exclusion criteria. Guidance on
      standardisation of inclusion and exclusion criteria for nsLBP trials will
      increase clinical homogeneity, facilitating greater interpretation of between
      trial comparisons and meta-analyses. We propose a template for reporting
      inclusion and exclusion criteria.

PMID- 29650016
TI  - Evolution of computational models in BioModels Database and the Physiome Model
      Repository.
AB  - BACKGROUND: A useful model is one that is being (re)used. The development of a
      successful model does not finish with its publication. During reuse, models are
      being modified, i.e. expanded, corrected, and refined. Even small changes in the
      encoding of a model can, however, significantly affect its interpretation. Our
      motivation for the present study is to identify changes in models and make them
      transparent and traceable. METHODS: We analysed 13734 models from BioModels
      Database and the Physiome Model Repository. For each model, we studied the
      frequencies and types of updates between its first and latest release. To
      demonstrate the impact of changes, we explored the history of a Repressilator
      model in BioModels Database. RESULTS: We observed continuous updates in the
      majority of models. Surprisingly, even the early models are still being modified.
      We furthermore detected that many updates target annotations, which improves the
      information one can gain from models. To support the analysis of changes in model
      repositories we developed MoSt, an online tool for visualisations of changes in
      models. The scripts used to generate the data and figures for this study are
      available from GitHub https://github.com/binfalse/BiVeS-StatsGenerator and as a
      Docker image at https://hub.docker.com/r/binfalse/bives-statsgenerator/ . The
      website https://most.bio.informatik.uni-rostock.de/ provides interactive access
      to model versions and their evolutionary statistics. CONCLUSION: The reuse of
      models is still impeded by a lack of trust and documentation. A detailed and
      transparent documentation of all aspects of the model, including its provenance,
      will improve this situation. Knowledge about a model's provenance can avoid the
      repetition of mistakes that others already faced. More insights are gained into
      how the system evolves from initial findings to a profound understanding. We
      argue that it is the responsibility of the maintainers of model repositories to
      offer transparent model provenance to their users.

PMID- 29650018
TI  - Health conditions and lifestyle risk factors of adults living in Puerto Rico: a
      cross-sectional study.
AB  - BACKGROUND: Puerto Rico is experiencing an economic and healthcare crisis, yet
      there are scarce recent and comprehensive reports on the population's health
      profile. We aimed to describe prevalent risk factors and health conditions of
      adults living in Puerto Rico and assess their interrelationship. METHODS:
      Participants (n = 380) aged 30-75y recruited from a 2015 convenience sample in
      primary care clinics in the San Juan, Puerto Rico metropolitan area answered
      cross-sectional interviewer-administered questionnaires on sociodemographic
      characteristics, lifestyle behaviors, self-reported medically-diagnosed diseases,
      health services, and psychosocial factors. Anthropometric measures were obtained.
      Logistic regression models assessed factors associated with having >=2
      cardiometabolic conditions or >= 2 chronic diseases. RESULTS: Most participants
      had completed >=college education (57%), had household income <$10,000/y (60%),
      received government-assisted food benefits (51%), and had health insurance (93%).
      Nearly 20% reported smoking, 27% alcohol use, 74% light/sedentary physical
      activity, 51% sleeping difficulties, and 36% self-rated fair/poor diet. Social
      support was moderate, and 53% screened positive for depressive symptomatology.
      Abdominal obesity was observed in 33% of men and 76% of women (p < 0.0001). Self
      reported medically-diagnosed conditions included hypertension (39%), anxiety
      (30%), obesity (28%), arthritis (26%), hypercholesterolemia (24%), depression
      (22%), respiratory problems (21%), and diabetes (21%). Higher odds of having >=2
      cardiometabolic conditions (37%) was observed among participants aged >=50y, with
      sedentary physical activity, and self-rated fair/poor diet. Odds of having >=2
      chronic diseases (62%) were higher among >=50y, sleeping difficulties, > 2 h/day
      television, and self-rated fair/poor diet. Participants obtained (79%) and
      trusted (92%) health information from physicians. While most participants with a
      cardiometabolic condition reported receiving medical recommendations on diet (>
      73%) and physical activity (> 67%), fewer followed them (< 67% and < 53%,
      respectively), yet most adhered to medication treatments (> 73%). Participants
      following medical recommendations were more likely to report healthy vs. poor
      behaviors (90% vs. 75%, self-rated diet); (73% vs. 56%, physical activity).
      CONCLUSIONS: Adults living in Puerto Rico have multiple lifestyles risk factors
      and high prevalence of chronic diseases, namely cardiometabolic and psychological
      conditions. Comprehensive epidemiological studies are needed to identify
      contributors to chronic disease, including lifestyle behaviors. Concerted multi
      level public health and clinical programs should be prioritized to help this
      population improve their health.

PMID- 29650019
TI  - The effect of North Carolina free clinics on hospitalizations for ambulatory care
      sensitive conditions among the uninsured.
AB  - BACKGROUND: Free clinics are volunteer based organizations that provide health
      care services to low-income individuals for free or minimal cost. Communities
      served by a free clinic can provide ambulatory care services for uninsured
      individuals, reducing reliance on costly hospital admissions for ambulatory care
      sensitive conditions. This study examines whether free clinics in North Carolina
      reduce hospitalizations for ambulatory care sensitive conditions for uninsured
      adults. METHODS: The study used North Carolina hospital discharge data from 2003
      to 2007, restricted to uninsured adults residing in North Carolina (N = 270,325).
      Prevention Quality Indicators identified hospitalizations for ambulatory care
      sensitive conditions. The entry of new free clinics in some counties during this
      time period in conjunction with county-level and year fixed effects allows the
      logistic regression analysis to simulate a pre/post study design. RESULTS:
      Discharges for ambulatory care sensitive conditions constituted 12.6% of the
      sample. Despite the limited coverage provided by free clinics, which serve 5.5%
      of the uninsured in North Carolina, uninsured adults in counties served by a free
      clinic had an 8.0% reduced odds of a hospitalization being for an ambulatory care
      sensitive condition. When the model is limited to ambulatory care sensitive
      conditions related to chronic conditions, the odds of a hospitalization of an
      uninsured adult for an ambulatory care sensitive condition in counties served by
      a free clinic is reduced by 9.0%. CONCLUSION: Free clinics are effective
      providers of primary care services for uninsured individuals, particularly for
      those with chronic conditions. To enhance this impact by increasing free clinics'
      reach, state and local policy makers should support and encourage development of
      free clinics in high need areas.

PMID- 29650017
TI  - Toll-like receptors in lupus nephritis.
AB  - The pathogenesis of systemic autoimmune diseases such as systemic lupus
      erythematosus (SLE) is based on the loss of self-tolerance against ubiquitous
      autoantigens involving all mechanisms of adaptive immunity. However, data
      accumulating over the last decade imply an important role also for numerous
      elements of innate immunity, namely the Toll-like receptors in the pathogenesis
      of SLE. Here we discuss their role in the most common organ complication of SLE,
      i.e. lupus nephritis. We summarize experimental and clinical data on the
      expression and functional contribution of the Toll-like receptors in immune
      complex glomerulonephritis, and intrarenal inflammation. Based on these
      discoveries Toll-like receptors are evolving as therapeutic targets for the
      treatment of SLE and lupus nephritis.

PMID- 29650020
TI  - Understanding community-based participatory research through a social movement
      framework: a case study of the Kahnawake Schools Diabetes Prevention Project.
AB  - BACKGROUND: A longstanding challenge of community-based participatory research
      (CBPR) has been to anchor evaluation and practice in a relevant theoretical
      framework of community change, which articulates specific and concrete evaluative
      benchmarks. Social movement theories provide a broad range of theoretical tools
      to understand and facilitate social change processes, such as those involved in
      CBPR. Social movement theories have the potential to provide a coherent
      representation of how mobilization and collective action is gradually developed
      and leads to systemic change in the context of CBPR. The current study builds on
      a social movement perspective to assess the processes and intermediate outcomes
      of a longstanding health promotion CBPR project with an Indigenous community, the
      Kahnawake Schools Diabetes Prevention Project (KDSPP). METHODS: This research
      uses a case study design layered on a movement-building evaluation framework,
      which allows progress to be tracked over time. Data collection strategies
      included document (scientific and organizational) review (n = 51) and talking
      circles with four important community stakeholder groups (n = 24). RESULTS:
      Findings provide an innovative and chronological perspective of the evolution of
      KSDPP as seen through a social movement lens, and identify intermediate outcomes
      associated with different dimensions of movement building achieved by the project
      over time (mobilization, leadership, vision and frames, alliance and
      partnerships, as well as advocacy and action strategies). It also points to areas
      of improvement for KSDPP in building its potential for action. CONCLUSION: While
      this study's results are directly relevant and applicable to the local context of
      KSDPP, they also highlight useful lessons and conclusions for the planning and
      evaluation of other long-standing and sustainable CBPR initiatives. The
      conceptual framework provides meaningful benchmarks to track evidence of progress
      in the context of CBPR. Findings from the study offer new ways of thinking about
      the evaluation of CBPR projects and their progress by drawing on frameworks that
      guide other forms of collective action.

PMID- 29650021
TI  - Overexpression of a type III PKS gene affording novel violapyrones with enhanced
      anti-influenza A virus activity.
AB  - BACKGROUND: Type III polyketide synthases (PKSs) are simple homodimer
      ketosynthases that distribute across plants, fungi, and bacteria, catalyzing
      formation of pyrone- and resorcinol-types aromatic polyketides with various
      bioactivities. The broad substrate promiscuity displayed by type III PKSs makes
      them wonderful candidates for expanding chemical diversity of polyketides.
      RESULTS: Violapyrone B (VLP B, 10), an alpha-pyrone compound produced by deepsea
      derived Streptomyces somaliensis SCSIO ZH66, is encoded by a type III PKS VioA.
      We overexpressed VioA in three different hosts, including Streptomyces coelicolor
      M1146, Streptomyces sanyensis FMA as well as the native producer S. somaliensis
      SCSIO ZH66, leading to accumulation of different violapyrone compounds. Among
      them, S. coelicolor M1146 served as the host producing the most abundant
      violapyrones, from which five new (2-4, 7 and 12) and nine known (1, 5, 6, 8-11,
      13 and 14) compounds were identified. Anti-influenza A (H1N1) virus activity of
      these compounds was then evaluated using ribavirin as a positive control (IC50 =
      112.9 MUM), revealing that compounds 11-14 showed considerable activity with IC50
      values of 112.7, 26.9, 106.7 and 28.8 MUM, respectively, which are significantly
      improved as compared to that of VLP B (10) (IC50 > 200 MUM). The productions of
      10 and 13 were increased by adding P450 inhibitor metyrapone. In addition, site
      directed mutagenesis experiment led to demonstration of the residue S242 to be
      essential for the activity of VioA. CONCLUSIONS: Biological background of the
      expression hosts is an important factor impacting on the encoding products of
      type III PKSs. By using S. coelicolor M1146 as cell factory, we were able to
      generate fourteen VLPs compounds. Anti-H1N1 activity assay suggested that the
      lipophilic nature of the alkyl chains of VLPs plays an important role for the
      activity, providing valuable guidance for further structural optimization of
      VLPs.

PMID- 29650022
TI  - Dr. Jekyll and Mr. Hyde: MAP17's up-regulation, a crosspoint in cancer and
      inflammatory diseases.

PMID- 29650023
TI  - Sustained impact of energy-dense TV and online food advertising on children's
      dietary intake: a within-subject, randomised, crossover, counter-balanced trial.
AB  - BACKGROUND: Policies restricting children's exposure to unhealthy food marketing
      have been impeded by the lack of evidence showing a direct link between food
      advertising exposure and children's energy intake and body weight. Food
      advertising exposure increases children's immediate food consumption, but whether
      this increased intake is compensated for at later eating occasions is not known;
      consequently the sustained effect on diets remains unclear. METHODS: We conducted
      a within-subject, randomised, crossover, counterbalanced study across four, six
      day holiday camps in New South Wales, Australia between April 2016 and January
      2017. Children (7-12 years, n = 160) were recruited via local schools, email
      networks and social media. Two gender- and age-balanced groups were formed for
      each camp (n = 20), randomised to either a multiple- or single- media condition
      and exposed to food and non-food advertising in an online game and/or a
      television cartoon. Children's food consumption (kilojoules) was measured at a
      snack immediately after exposure and then at lunch later in the day. Linear mixed
      models were conducted to examine relationships between food advertising exposure
      and dietary intake, taking into account gender, age and weight status. RESULTS:
      All children in the multiple-media condition ate more at a snack after exposure
      to food advertising compared with non-food advertising; this was not compensated
      for at lunch, leading to additional daily food intake of 194 kJ (95% CI 80-308, p
      = 0.001, d = 0.2). Exposure to multiple-media food advertising compared with a
      single-media source increased the effect on snack intake by a difference of 182
      kJ (95% CI 46-317, p = 0.009, d = 0.4). Food advertising had an increased effect
      among children with heavier weight status in both media groups. CONCLUSION:
      Online ('advergame') advertising combined with TV advertising exerted a stronger
      influence on children's food consumption than TV advertising alone. The lack of
      compensation at lunch for children's increased snack intake after food
      advertising exposure suggests that unhealthy food advertising exposure
      contributes to a positive energy-gap, which could cumulatively lead to the
      development of overweight. TRIAL REGISTRATION: Australian New Zealand Clinical
      Trials Registry, number ACTRN12617001230347 (Retrospectively registered).

PMID- 29650025
TI  - Effectiveness of health education as an intervention designed to prevent female
      genital mutilation/cutting (FGM/C): a systematic review.
AB  - BACKGROUND: Female Genital Mutilation/Cutting (FGM/C) is a harmful practice that
      violates the human rights of women and girls. Despite global efforts to restrict
      the practice, there have been few reports on major positive changes to the
      problem. Health education interventions have been successful in preventing
      various health conditions and promoting service use. They have also been regarded
      as promising interventions for preventing FGM/C. The objective of this systematic
      review is to synthesise findings of studies about effectiveness of health
      education as an intervention to prevent FGM/C. METHODS: The electronic databases
      searched were MEDLINE, EMBASE, Cochrane library, Web of Science, Psych INFO,
      CINAHL and ASSIA. Our search included papers published in the English language
      without date limits. Study quality was assessed using the Mixed Methods Appraisal
      Tool (MMAT). A predesigned data recording form was used to extract data from the
      included studies which were summarised by comparing similar themes. RESULTS:
      Twelve out of 359 individual studies met our inclusion criteria. Seven studies
      were quantitative, three were qualitative and two used mixed methods. Six studies
      tested before and after the interventions, four studies assessed the
      effectiveness of previous interventions used by different research teams and two
      studies endorsed the intervention. Four main factors emerged and were associated
      with facilitating or hindering the effectiveness of health education
      interventions: sociodemographic factors; socioeconomic factors; traditions and
      beliefs; and intervention strategy, structure and delivery. CONCLUSIONS: It is
      vital to target factors associated with facilitating or hindering the
      effectiveness of health education for FGM/C. This increases the possibility of
      effective, collective change in behaviour and attitude which leads to the
      sustainable prevention of FGM/C and ultimately the improved reproductive health
      and well-being of individuals and communities.

PMID- 29650024
TI  - VGLUT1 or VGLUT2 mRNA-positive neurons in spinal trigeminal nucleus provide
      collateral projections to both the thalamus and the parabrachial nucleus in rats.
AB  - The trigemino-thalamic (T-T) and trigemino-parabrachial (T-P) pathways are
      strongly implicated in the sensory-discriminative and affective/emotional aspects
      of orofacial pain, respectively. These T-T and T-P projection fibers originate
      from the spinal trigeminal nucleus (Vsp). We previously determined that many
      vesicular glutamate transporter (VGLUT1 and/or VGLUT2) mRNA-positive neurons were
      distributed in the Vsp of the adult rat, and most of these neurons sent their
      axons to the thalamus or cerebellum. However, whether VGLUT1 or VGLUT2 mRNA
      positive projection neurons exist that send their axons to both the thalamus and
      the parabrachial nucleus (PBN) has not been reported. Thus, in the present study,
      dual retrograde tract tracing was used in combination with fluorescence in situ
      hybridization (FISH) for VGLUT1 or VGLUT2 mRNA to identify the existence of
      VGLUT1 or VGLUT2 mRNA neurons that send collateral projections to both the
      thalamus and the PBN. Neurons in the Vsp that send collateral projections to both
      the thalamus and the PBN were mainly VGLUT2 mRNA-positive, with a proportion of
      90.3%, 93.0% and 85.4% in the oral (Vo), interpolar (Vi) and caudal (Vc)
      subnucleus of the Vsp, respectively. Moreover, approximately 34.0% of the
      collateral projection neurons in the Vc showed Fos immunopositivity after
      injection of formalin into the lip, and parts of calcitonin gene-related peptide
      (CGRP)-immunopositive axonal varicosities were in direct contact with the Vc
      collateral projection neurons. These results indicate that most collateral
      projection neurons in the Vsp, particularly in the Vc, which express mainly
      VGLUT2, may relay orofacial nociceptive information directly to the thalamus and
      PBN via axon collaterals.

PMID- 29650027
TI  - In regard to "Tran A, Zhang J, Woods K, Yu V, Nguyen D, Gustafson G, Rosen L,
      Sheng K. Treatment planning comparison of IMPT, VMAT and 4pi radiotherapy for
      prostate cases. Radiation oncology. 2017 Jan 11; 12(1):10".
AB  - This article describe the three dimensional geometrical incompetency of the term
      "4pi radiotherapy"; frequently used in radiation oncology to establish the
      superiority (or rather complexity) of particular kind of external beam delivery
      technique. It was claimed by several researchers, to obtain 4pic solid angle at
      target centre created by the tele-therapy delivery machine in three dimensional
      Euclidian space. However with the present design of linear accelerator (or any
      other tele-therapy machine) it is not possible to achieve more than 2pic with the
      allowed boundary condition of 0 <= Gnatry position<=pic and [Formula: see
      text]<=Couch Position<=[Formula: see text] .This article describes why it is not
      possible to achieve a 4pic solid angle at any point in three dimensional
      Euclidian spaces. This article also recommends not to use the terminology "4pi
      radiotherapy" for describing any external beam technique or its complexity as
      this term is geometrically wrong.

PMID- 29650026
TI  - SQUID: transcriptomic structural variation detection from RNA-seq.
AB  - Transcripts are frequently modified by structural variations, which lead to fused
      transcripts of either multiple genes, known as a fusion gene, or a gene and a
      previously non-transcribed sequence. Detecting these modifications, called
      transcriptomic structural variations (TSVs), especially in cancer tumor
      sequencing, is an important and challenging computational problem. We introduce
      SQUID, a novel algorithm to predict both fusion-gene and non-fusion-gene TSVs
      accurately from RNA-seq alignments. SQUID unifies both concordant and discordant
      read alignments into one model and doubles the precision on simulation data
      compared to other approaches. Using SQUID, we identify novel non-fusion-gene TSVs
      on TCGA samples.

PMID- 29650028
TI  - A rare presentation of pulmonary sarcoidosis as a solitary lung mass: a case
      report.
AB  - BACKGROUND: Sarcoidosis is a multisystem, chronic granulomatous disease of
      unknown etiology that predominantly affects the lungs. Pulmonary sarcoidosis
      classically presents with constitutional symptoms and computed tomographic scan
      findings of bilateral, symmetric micronodules in a peribronchovascular
      distribution with upper and middle lung zone predominance accompanied by
      bilateral, symmetric hilar lymphadenopathy. A solitary lung mass is a rare
      finding for pulmonary sarcoidosis, and with its associated constitutional
      symptoms, it strongly mimics a malignancy. We aimed to provide further insight
      into the broad differential diagnosis of a lung mass by describing our
      experiences in the care of a patient who presented with clinical and radiographic
      features of lung cancer who was ultimately found to have an atypical
      manifestation of stage II pulmonary sarcoidosis. CASE PRESENTATION: A 44-year-old
      African American woman with a history of childhood asthma and type 2 diabetes
      mellitus presented with shortness of breath. After being treated for a presumed
      asthma exacerbation with prednisone, she experienced worsening dyspnea, night
      sweats, and unintentional weight loss. Further evaluation revealed a large left
      lower lobe mass and hilar lymphadenopathy. A computed tomography-guided biopsy of
      the lung mass revealed a multifocal non-necrotizing granuloma with multinucleated
      giant cells. Although consistent with sarcoidosis, this finding could represent a
      sarcoid-like reaction secondary to an occult malignancy. A more extensive repeat
      biopsy via bronchoscopy and mediastinoscopy revealed granulomatous inflammation
      without evidence of malignancy or infection. These procedures confirmed the
      diagnosis of pulmonary sarcoidosis, and she was started on treatment with high
      dose prednisone. Her treatment course was complicated by hyperglycemia
      necessitating insulin therapy, but after 3 months of therapy, she reported
      improvement in her dyspnea, and repeat imaging revealed a significant decrease in
      the size of the lung mass and lymphadenopathy. Given her clinical and
      radiographic response, she was continued on a prednisone taper. CONCLUSIONS:
      Atypical manifestations of pulmonary sarcoidosis are diagnostically challenging
      because the clinical and radiographic features of the disease mimic those of a
      malignancy. We aimed to illustrate a unique etiology of a lung mass and the
      importance of maintaining a broad differential diagnosis. Nonetheless, with the
      possibility of a malignancy, a high index of suspicion is necessary for timely
      diagnosis and optimal management.

PMID- 29650029
TI  - The dose distribution in dominant intraprostatic tumour lesions defined by
      multiparametric MRI and PSMA PET/CT correlates with the outcome in patients
      treated with primary radiation therapy for prostate cancer.

PMID- 29650030
TI  - Harnessing Qatar Biobank to understand type 2 diabetes and obesity in adult
      Qataris from the First Qatar Biobank Project.
AB  - BACKGROUND: Human tissues are invaluable resources for researchers worldwide.
      Biobanks are repositories of such human tissues and can have a strategic
      importance for genetic research, clinical care, and future discoveries and
      treatments. One of the aims of Qatar Biobank is to improve the understanding and
      treatment of common diseases afflicting Qatari population such as obesity and
      diabetes. METHODS: In this study we apply a panorama of state-of-the-art
      statistical methods and machine learning algorithms to investigate associations
      and risk factors for diabetes and obesity on a sample of 1000 Qatari population.
      RESULTS: Regarding diabetes, we identified pronounced associations and risk
      factors in Qatari population including magnesium, chloride, c-peptide of insulin,
      insulin, and uric acid. Similarly, for obesity, significant associations and risk
      factors include insulin, c-peptide of insulin, albumin, and uric acid. Moreover,
      our study has revealed interactions of hypomagnesemia with HDL-C, triglycerides,
      and free thyroxine. CONCLUSIONS: Our study strongly confirms known associations
      and risk factors associated with diabetes and obesity in Qatari population as
      previously found in other population studies in different parts of the world.
      Moreover, interactions of hypomagnesemia with other associations and risk factors
      merit further investigations.

PMID- 29650032
TI  - Biosecurity and animal disease management in organic and conventional Swedish
      dairy herds: a questionnaire study.
AB  - BACKGROUND: Good animal health is a notion that is germane to organic dairy
      production, and it is expected that such herds would pay significant attention on
      the health of their animals. However, it is not known if the applied animal
      disease management is actually more adequate in organic dairy cattle herds than
      in conventional dairy herds. A questionnaire study on biosecurity and animal
      disease management activities was therefore conducted among Swedish farmers with
      organic and conventional dairy cattle herds. RESULTS: A total of 192 useable
      questionnaires were returned; response rates of 30.3 and 20.2% for organic and
      conventional farmers, respectively. Herd characteristics of the two herd types
      were very similar, except that pipeline/tie-stall systems were less common in
      organic farms and that organic farmers had a higher education level than their
      conventional counterparts. Also, very few systematic differences in general or
      specific disease management activities were observed between the two types of
      farms. The main exceptions being how milk from cows during antibiotic treatment
      was used, views on policy actions in relation to antibiotic use, and attitudes
      towards calling for veterinary support. Using milk from cows during antibiotic
      treatment was more common in conventional herds, although it was mainly given to
      bull calves. Farmers of organic herds were more positive to policy actions to
      reduce the use and need for antibiotics, and they reported waiting longer before
      contacting a veterinarian for calves with diarrhoea and cows with subclinical
      mastitis. CONCLUSIONS: The stated biosecurity and animal disease management was
      relatively equal in Swedish organic and conventional dairy herds. Our results
      thus indicate that animal health is as important in conventionally managed dairy
      herds in Sweden as in organically managed herds.

PMID- 29650031
TI  - The physiological role of Motin family and its dysregulation in tumorigenesis.
AB  - Members in Motin family, or Angiomotins (AMOTs), are adaptor proteins that
      localize in the membranous, cytoplasmic or nuclear fraction in a cell context
      dependent manner. They control the bioprocesses such as migration, tight junction
      formation, cell polarity, and angiogenesis. Emerging evidences have demonstrated
      that AMOTs participate in cancer initiation and progression. Many of the previous
      studies have focused on the involvement of AMOTs in Hippo-YAP1 pathway. However,
      it has been controversial for years that AMOTs serve as either positive or
      negative growth regulators in different cancer types because of the various
      cellular origins. The molecular mechanisms of these opposite roles of AMOTs
      remain elusive. This review comprehensively summarized how AMOTs function
      physiologically and how their dysregulation promotes or inhibits tumorigenesis.
      Better understanding the functional roles of AMOTs in cancers may lead to an
      improvement of clinical interventions as well as development of novel therapeutic
      strategies for cancer patients.

PMID- 29650033
TI  - Enterovirus serotypes in patients with central nervous system and respiratory
      infections in Viet Nam 1997-2010.
AB  - BACKGROUND: Enteroviruses are the most common causative agents of human illness.
      Enteroviruses have been associated with regional and global epidemics, recently,
      including with severe disease (Enterovirus A71 and D68), and are of interest as
      emerging viruses. Here, we typed Enterovirus A-D (EV) from central nervous system
      (CNS) and respiratory infections in Viet Nam. METHODS: Data and specimens from
      prospective observational clinical studies conducted between 1997 and 2010 were
      used. Species and serotypes were determined using type-specific RT-PCR and viral
      protein 1 or 4 (VP1, VP4) sequencing. RESULTS: Samples from patients with CNS
      infection (51 children - 10 CSF and 41 respiratory/rectal swabs) and 28 adults
      (28 CSF) and respiratory infection (124 children - 124 respiratory swabs) were
      analysed. Twenty-six different serotypes of the four Enterovirus species (A-D)
      were identified, including EV-A71 and EV-D68. Enterovirus B was associated with
      viral meningitis in children and adults. Hand, foot and mouth disease associated
      Enteroviruses A (EV-A71 and Coxsackievirus [CV] A10) were detected in children
      with encephalitis. Diverse serotypes of all four Enterovirus species were found
      in respiratory samples, including 2 polio-vaccine viruses, but also 8 CV-A24 and
      8 EV-D68. With the exception of EV-D68, the relevance of these viruses in
      respiratory infection remains unknown. CONCLUSION: We describe the diverse
      spectrum of enteroviruses from patients with CNS and respiratory infections in
      Viet Nam between 1997 and 2010. These data confirm the global circulation of
      Enterovirus genera and their associations and are important for clinical
      diagnostics, patient management, and outbreak response.

PMID- 29650034
TI  - COMplex Fracture Orthopedic Rehabilitation (COMFORT) - Real-time visual
      biofeedback on weight bearing versus standard training methods in the treatment
      of proximal femur fractures in the elderly: study protocol for a multicenter
      randomized controlled trial.
AB  - BACKGROUND: Proximal femur fractures are a common injury after low energy trauma
      in the elderly. Most rehabilitation programs are based on restoring mobility and
      early resumption of weight-bearing. However, therapy compliance is low in
      patients following lower extremity fractures. Moreover, little is known about the
      relevance of gait parameters and how to steer the rehabilitation after proximal
      femur fractures in the elderly. Therefore, the aim of this prospective,
      randomized controlled trial is to gain insight in gait parameters and evaluate if
      real-time visual biofeedback can improve therapy compliance after proximal femur
      fractures in the elderly. METHODS: This is a two-arm, parallel-design,
      prospective, randomized controlled trial. Inclusion criteria are age >= 60 years,
      a proximal femur fracture following low energy trauma, and unrestricted-weight
      bearing. Exclusion criteria are cognitive impairment and limited mobility before
      trauma. Participants are randomized into either the control group, which receives
      care as usual, or the intervention group, which receives real-time visual
      biofeedback about weight-bearing during gait in addition to care as usual.
      Spatiotemporal gait parameters will be measured in 94 participants per group
      during a 30-m walk with an ambulatory biofeedback system (SensiStep). The
      progress of rehabilitation will be evaluated by the primary outcome parameters
      maximum peak load and step duration in relation to the discharge date. Secondary
      outcome parameters include other spatiotemporal gait parameters in relation to
      discharge date. Furthermore, the gait parameters will be related to three
      validated clinical tests: Elderly Mobility Scale; Functional Ambulation
      Categories; and Visual Analogue Scale. The primary hypothesis is that
      participants in the intervention group will show improved and faster
      rehabilitation compared to the control group. DISCUSSION: The first aim of this
      multicenter trial is to investigate the normal gait patterns after proximal femur
      fractures in the elderly. The use of biofeedback systems during rehabilitation
      after proximal femur fractures in the elderly is promising; therefore, the second
      aim is to investigate the effect of real-time visual biofeedback on gait after
      proximal femur fractures in the elderly. This could lead to improved outcome. In
      addition, analysis of the population may indicate characteristics of subgroups
      that benefit from feedback, making a differentiated approach in rehabilitation
      strategy possible. TRIAL REGISTRATION: TrialRegister.nl, NTR6794 . Registered on
      31 October 2017.

PMID- 29650035
TI  - Image-guided radiotherapy reduces the risk of under-dosing high-risk prostate
      cancer extra-capsular disease and improves biochemical control.
AB  - BACKGROUND: To determine if reduced dose delivery uncertainty is associated with
      daily image-guidance (IG) and Prostate Specific Antigen Relapse Free Survival
      (PRFS) in intensity-modulated radiotherapy (IMRT) of high-risk prostate cancer
      (PCa). METHODS: Planning data for consecutive PCa patients treated with IMRT (n =
      67) and IG-IMRT (n = 35) was retrieved. Using computer simulations of setup
      errors, we estimated the patient-specific uncertainty in accumulated treatment
      dose distributions for the prostate and for posterolateral aspects of the gland
      that are at highest risk for extra-capsular disease. Multivariate Cox regression
      for PRFS considering Gleason score, T-stage, pre-treatment PSA, number of
      elevated clinical risk factors (T2c+, GS7+ and PSA10+), nomogram-predicted risk
      of extra-capsular disease (ECD), and dose metrics was performed. RESULTS: For
      IMRT vs. IG-IMRT, plan dosimetry values were similar, but simulations revealed
      uncertainty in delivered dose external to the prostate was significantly
      different, due to positioning uncertainties. A patient-specific interaction term
      of the risk of ECD and risk of low dose to the ECD (p = 0.005), and the number of
      elevated clinical risk factors (p = 0.008), correlate with reduced PRFS.
      CONCLUSIONS: Improvements in PSA outcomes for high-risk PCa using IG-IMRT vs.
      IMRT without IG may be due to improved dosimetry for ECD.

PMID- 29650037
TI  - Open-label, randomized multicentre phase II study to assess the efficacy and
      tolerability of sunitinib by dose administration regimen (dose modification or
      dose interruptions) in patients with advanced or metastatic renal cell carcinoma:
      study protocol of the SURF trial.
AB  - BACKGROUND: Sunitinib is a tyrosine kinase inhibitor approved in the first-line
      metastatic renal cell carcinoma (MRCC) setting at the dose of 50 mg daily for 4
      weeks followed by a pause of 2 weeks. Due to toxicity, this standard schedule (50
      mg daily 4/2) can induce up to 50% of sunitinib dose modification (reduction
      and/or interruption). The current recommendation in such case is to reduce the
      dose to 37.5 mg per day (standard schedule 4/2). Recent data highlight an
      alternative schedule: 2 weeks of treatment followed by 1 week of pause
      (experimental schedule 2/1). The SURF trial is set up to evaluate prospectively
      experimental schedule 2/1 when toxicity occurs. This article displays the key
      elements of the study protocol. METHODS/DESIGN: SURF [NCT02689167] is a
      prospective, randomized, open-label phase IIb study. Patients are included at
      sunitinib initiation while receiving standard schedule 4/2 (50 mg daily)
      according to the marketing authorization indication. When a dose adjustment of
      sunitinib is required, patients are randomized between standard schedule 4/2
      (37.5 mg daily) and experimental schedule 2/1 (50 mg daily). Key eligibility
      criteria are the following: patients with locally advanced inoperable or MRCC who
      are starting first-line treatment with sunitinib, with histologically or
      cytologically confirmed renal cancer clear cell variant or with a clear cell
      component, and with Karnofsky performance status >=70%. The primary objective is
      to assess the median duration of sunitinib treatment (DOT) in each group. The key
      secondary objectives are progression-free survival, overall survival, time to
      randomization, objective response rate, safety, sunitinib dose intensity, health
      related quality of life, and the description of main drivers triggering
      randomization. We hypothesized that experimental schedule 2/1 would result in an
      improvement in median DOT from 6 to 8.5 months. It was estimated that 112
      patients would be needed in each arm during 24 months. In order to take into
      account the possibility of treatment discontinuation before randomization, 248
      patients are necessary. DISCUSSION: The SURF trial is asking a pragmatic question
      adapted to the current practice on what is the best way to adapt sunitinib when
      treatment-related adverse events occur. The results of the SURF trial will bring
      high-value data to support the use of an alternative schedule in sunitinib
      treatment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02689167 . Registered on 26
      February 2016.

PMID- 29650036
TI  - Prevalence and molecular characterization of Cryptosporidium spp. and Giardia
      duodenalis in deer in Henan and Jilin, China.
AB  - BACKGROUND: Little is known about the prevalence and zoonotic potential of
      Cryptosporidium spp. and Giardia duodenalis in deer in China. In this study, 662
      fecal samples were collected from 11 farms in Henan and Jilin Provinces between
      July 2013 and August 2014, and were screened for the presence of Cryptosporidium
      and G. duodenalis with genotyping and subtyping methods. RESULTS: Cryptosporidium
      spp. and G. duodenalis were detected in 6.80% (45/662) and 1.21% (5/662) of
      samples, respectively. Six Cryptosporidium species/genotypes were identified
      based on the small subunit ribosomal ribonucleic acid (SSU rRNA) gene: C. parvum
      (n = 11); C. andersoni (n = 5); C. ubiquitum (n = 3); C. muris (n = 1); C. suis
      like (n = 1); and Cryptosporidium deer genotype (n = 24). When five of the 11 C.
      parvum isolates were subtyped by sequencing the 60 kDa glycoprotein (gp60) gene,
      zoonotic subtypes IIaA15G2R2 (n = 4) and IIdA19G1 (n = 1) were found. According
      to a subtype analysis, three C. ubiquitum isolates belonged to XIIa subtype 2. In
      contrast, only assemblage E was detected in the five Giardia-positive samples
      with small subunit ribosomal ribonucleic acid (SSU rRNA) gene sequencing.
      CONCLUSIONS: To our knowledge, this is the first study to report C. andersoni, as
      well as C. parvum zoonotic subtypes IIaA15G2R2 and IIdA19G1 in cervids. These
      data, though limited, suggest that cervids may be a source of zoonotic
      Cryptosporidium and Giardia. Cervids in the present study are likely to be of low
      zoonotic potential to humans, and more molecular epidemiological studies are
      required to clarify the prevalence and public health significance of
      Cryptosporidium and G. duodenalis in cervids throughout China.

PMID- 29650038
TI  - A lifelong study of a pack Rhodesian ridgeback dogs reveals subclinical and
      clinical tick-borne Anaplasma phagocytophilum infections with possible
      reinfection or persistence.
AB  - BACKGROUND: Various tick-borne infections often occur without specific clinical
      signs and are therefore notoriously hard to diagnose separately in veterinary
      practice. Longitudinal studies over multiple tick seasons performing clinical,
      serological and molecular investigations in parallel, may elucidate the
      relationship between infection and disease. In this regard, six related Rhodesian
      Ridgeback dogs living as a pack became subject of lifetime studies due to ongoing
      tick infestations and recurring clinical problems. Blood samples for diagnostic
      tests were obtained throughout the years 2000 to 2009. METHODS: Data collected
      from clinical observations, hemograms, serology and detection of Anaplasma
      phagocytophilum, either by microscopy or by DNA amplification and typing, were
      placed in a time line. This dataset essentially presents as a prospective study
      enabling the association of the Anaplasma infections with occurring disease.
      RESULTS: All six dogs were infected, and two of them developed particular
      clinical symptoms that could be associated with Anaplasma infections over time.
      More specifically, episodes of general malaise with fever and purpura with
      thrombocytopenia and bacterial inclusions in granulocytes, were found
      concurrently with Anaplasma DNA and specific antibodies in peripheral blood
      samples. DNA from A. phagocytophilum variant 4 (of 16S rRNA) was found in
      multiple and sequential samples. DNA-sequences from variant 1 and the human
      granulocytic ehrlichiosis (HGE) agent were also detected. CONCLUSIONS: In this
      study two lifelong cases of canine anaplasmosis (CGA) are presented. The data
      show that dogs can be naturally infected concurrently with A. phagocytophilum
      variant 1, variant 4 and the HGE agent. The ongoing presence of specific
      antibodies and Anaplasma DNA in one dog indicates one year of persisting
      infection. Treatment with doxycycline during recurring clinical episodes in the
      other dog resulted in transient clinical improvement and subsequent disappearance
      of specific antibodies and DNA suggesting that re-infection occurred.

PMID- 29650039
TI  - Carbon black suppresses the osteogenesis of mesenchymal stem cells: the role of
      mitochondria.
AB  - BACKGROUND: The rapid increase in carbon black poses threats to human health. We
      evaluated the effect of CB (Printex 90) on the osteogenesis of bone-marrow
      derived mesenchymal stem cells (MSCs). Mitochondria play an important role in the
      osteogenesis of MSCs and are potential targets of nanomaterials, so we studied
      the role of mitochondria in the CB Printex 90-induced effects on osteogenesis.
      RESULTS: Low doses of Printex 90 (3 ng/mL and 30 ng/mL) that did not cause
      deleterious effects on MSCs' viability significantly inhibited osteogenesis of
      MSCs. Printex 90 caused down-regulation of osteoblastic markers, reduced activity
      of alkaline phosphatase (ALP), and poor mineralization of osteogenically induced
      MSCs. Cellular ATP production was decreased, mitochondrial respiration was
      impaired with reduced expression of ATPase, and the mitochondrial membrane was
      depolarized. The quantity and quality of mitochondria are tightly controlled by
      mitochondrial biogenesis, mitochondrial dynamics and mitophagy. The
      transcriptional co-activator and transcription factors for mitochondrial
      biogenesis, PGC-1alpha, Nrf1 and TFAM, were suppressed by Printex 90 treatment,
      suggesting that decreased biogenesis was caused by Printex 90 treatment during
      osteogenesis. Mitochondrial fusion and fission were significantly inhibited by
      Printex 90 treatment. PINK1 accumulated in Printex 90-treated cells, and more
      Parkin was recruited to mitochondria, indicating that mitophagy increased to
      remove the damaged mitochondria. CONCLUSIONS: This is the first report of the
      inhibitory effects of CB on the osteogenesis of MSCs and the involvement of
      mitochondria in CB Printex 90-induced suppression of MSC osteogenesis.

PMID- 29650040
TI  - Gene-level differential analysis at transcript-level resolution.
AB  - Compared to RNA-sequencing transcript differential analysis, gene-level
      differential expression analysis is more robust and experimentally actionable.
      However, the use of gene counts for statistical analysis can mask transcript
      level dynamics. We demonstrate that 'analysis first, aggregation second,' where
      the p values derived from transcript analysis are aggregated to obtain gene-level
      results, increase sensitivity and accuracy. The method we propose can also be
      applied to transcript compatibility counts obtained from pseudoalignment of
      reads, which circumvents the need for quantification and is fast, accurate, and
      model-free. The method generalizes to various levels of biology and we showcase
      an application to gene ontologies.

PMID- 29650041
TI  - Deep learning meets ontologies: experiments to anchor the cardiovascular disease
      ontology in the biomedical literature.
AB  - BACKGROUND: Automatic identification of term variants or acceptable alternative
      free-text terms for gene and protein names from the millions of biomedical
      publications is a challenging task. Ontologies, such as the Cardiovascular
      Disease Ontology (CVDO), capture domain knowledge in a computational form and can
      provide context for gene/protein names as written in the literature. This study
      investigates: 1) if word embeddings from Deep Learning algorithms can provide a
      list of term variants for a given gene/protein of interest; and 2) if biological
      knowledge from the CVDO can improve such a list without modifying the word
      embeddings created. METHODS: We have manually annotated 105 gene/protein names
      from 25 PubMed titles/abstracts and mapped them to 79 unique UniProtKB entries
      corresponding to gene and protein classes from the CVDO. Using more than 14 M
      PubMed articles (titles and available abstracts), word embeddings were generated
      with CBOW and Skip-gram. We setup two experiments for a synonym detection task,
      each with four raters, and 3672 pairs of terms (target term and candidate term)
      from the word embeddings created. For Experiment I, the target terms for 64
      UniProtKB entries were those that appear in the titles/abstracts; Experiment II
      involves 63 UniProtKB entries and the target terms are a combination of terms
      from PubMed titles/abstracts with terms (i.e. increased context) from the CVDO
      protein class expressions and labels. RESULTS: In Experiment I, Skip-gram finds
      term variants (full and/or partial) for 89% of the 64 UniProtKB entries, while
      CBOW finds term variants for 67%. In Experiment II (with the aid of the CVDO),
      Skip-gram finds term variants for 95% of the 63 UniProtKB entries, while CBOW
      finds term variants for 78%. Combining the results of both experiments, Skip-gram
      finds term variants for 97% of the 79 UniProtKB entries, while CBOW finds term
      variants for 81%. CONCLUSIONS: This study shows performance improvements for both
      CBOW and Skip-gram on a gene/protein synonym detection task by adding knowledge
      formalised in the CVDO and without modifying the word embeddings created. Hence,
      the CVDO supplies context that is effective in inducing term variability for both
      CBOW and Skip-gram while reducing ambiguity. Skip-gram outperforms CBOW and finds
      more pertinent term variants for gene/protein names annotated from the scientific
      literature.

PMID- 29650042
TI  - Dental pulp stem cells used to deliver the anticancer drug paclitaxel.
AB  - BACKGROUND: Understanding stem cell behavior as a delivery tool in cancer therapy
      is essential for evaluating their future clinical potential. Previous in-vivo
      studies proved the use of mesenchymal stem cells (MSCs) for local delivery of the
      commonest anticancer drug, paclitaxel (PTX). Dental pulp is a relatively abundant
      noninvasive source of MSCs. We assess dental pulp stem cells (DPSCs), for the
      first time, as anticancer drug carriers. Confocal Raman microscopy is a unique
      tool to trace drug and cell viability without labeling. METHODS: Drug uptake and
      cell apoptosis are identified through confocal Raman microscope. We traced
      translocation of cytochrome c enzyme from the mitochondria, as a biomarker for
      apoptosis, after testing both cancer and stem cells. The viability of stem cells
      was checked by means of confocal Raman microscope and by cytotoxicity assays.
      RESULTS: In this study, we prove that DPSCs can be loaded in vitro with the
      anticancerous drug without affecting their viability, which is later released in
      the culture medium of breast cancer cells (MCF-7 cells) in a time-dependent
      fashion. The induced cytotoxic damage in MCF-7 cells was observed consequently
      after PTX release by DPSCs. Additionally, quantitative Raman images of
      intracellular drug uptake in DPSCs and MCF-7 cells were obtained. Cytotoxic
      assays prove the DPSCs to be more resistant to PTX as compared to bone marrow
      derived MSCs, provided similar conditions. CONCLUSIONS: Applications of dental
      stem cells for targeted treatment of cancer could be a revolution to reduce
      morbidity due to chemotherapy, and to increase the efficacy of systemic cancer
      treatment.

PMID- 29650043
TI  - Experimental studies on effects of diet on Lawsonia intracellularis infections in
      fattening boars in a natural infection model.
AB  - BACKGROUND: Lawsonia intracellularis is one of the most economically important
      pathogens in swine production. This study tested the hypothesis that the
      composition of diets for pigs has an impact on the excretion of L.
      intracellularis in a natural infection model. RESULTS: Fifty boars (~ 90 kg BW)
      from a SPF-farm with a strict hygiene and management regime for reducing the
      spread of an L. intracellularis infection up to the beginning of the final
      fattening period were transported, regrouped and randomly allotted to groups of
      five animals each at the research facility. After a 1-week acclimatisation period
      groups were fed one of five diets 4 weeks before slaughter. These were either a
      finely ground pelleted diet (FP) or a coarsely ground meal diet (CM), both
      consisting of wheat (40.0%), barley (39.3%), soybean meal (16.0%), soybean oil
      (2.0%) and minor components. In the other meal diets parts of wheat, barley and
      soybean meal were substituted either with 22% cracked corn (CORN), 16.9% dried
      whey (WHEY) or 30% raw potato starch (RPS). The animals had a comparable
      serological status in a blocking-ELISA immediately before the start and at the
      end of the feeding experiment. Values increased significantly during the trial.
      In all subgroups (FP/CM/CORN/WHEY/RPS), shedding was detected in week 0 (genome
      equivalents = GE; log10 GE L. intracellularis/g faeces: 2.46 +/- 2.64/3.58 +/-
      2.54/3.43 +/- 2.37/2.30 +/- 3.16/2.58 +/- 2.73). The average number of L.
      intracellularis microbes in faeces during the trial period did not differ between
      the groups (log10 GE L. intracellularis/g faeces: 3.40 +/- 1.53/3.01 +/-
      1.41/3.80 +/- 1.71/3.98 +/- 2.20/4.08 +/- 2.13). In animals fed the WHEY-diet,
      significantly lower counts of L. intracellularis were found in the caecal
      content. The acetate content in the caecum was negatively correlated with the
      serological results at the end of the trial (r = - 0.36; P = 0.010). Butyrate
      concentrations in the caecal content were negatively correlated with the number
      of L. intracellularis in the caecum (r = - 0.32; P = 0.023). CONCLUSION:
      Therefore, this study provides preliminary evidence that there might be specific
      dietary effects on the course of a L. intracellularis infection.

PMID- 29650044
TI  - Human amnion-derived mesenchymal stem cells alleviate lung injury induced by
      white smoke inhalation in rats.
AB  - BACKGROUND: White smoke inhalation (WSI) is an uncommon but potentially deadly
      cause of acute lung injury and acute respiratory distress syndrome for which no
      effective pharmaceutical treatment has been developed. This study aimed to
      determine the protective effects of human amnion-derived mesenchymal stem cells
      (hAMSCs) against WSI-induced lung injury in rats. METHODS: hAMSCs were injected
      into rats via the tail vein 4 h after WSI. At 1, 3, 7, 14, and 28 days after cell
      injection, hAMSCs labeled with PKH26 in lung, heart, liver, and kidney tissues
      were observed by fluorescence microscopy. The lung injury score was determined by
      hematoxylin and eosin staining. Lung fibrosis was assessed by Masson's trichrome
      staining. The computed tomography (CT) score was assessed by CT scanning. The
      wet/dry weight ratio was calculated. The levels of interleukin (IL)-1beta, IL-6,
      and IL-10 were determined by enzyme-linked immunosorbent assays. The expression
      of surfactant protein (SP)-A, SP-C, and SP-D was measured by Western blotting.
      RESULTS: The injected hAMSCs were primarily distributed in the lung tissues in
      WSI-induced rats. Compared with the model and phosphate-buffered saline (PBS)
      group, hAMSC treatment led to reduced lung injury, lung fibrosis, CT score, and
      inflammation levels in WSI-induced mice. hAMSC treatment also resulted in
      increased cell retention in the lung, partial pressure of oxygen (PaO2), and
      PaO2/fraction of inspired oxygen (FiO2) levels, and pulmonary SP-A, SP-C, and SP
      D expression compared with that in the model and PBS group. CONCLUSIONS: hAMSCs
      are a potential cell-based therapy for WSI-induced lung injury.

PMID- 29650045
TI  - Characterization of the interaction between human decidua parietalis mesenchymal
      stem/stromal cells and natural killer cells.
AB  - BACKGROUND: Human decidua parietalis mesenchymal stem/multipotent stromal cells
      (DPMSCs) have unique phenotypic and functional properties that make them
      promising candidates for cell-based therapy. Here, we investigated DPMSC
      interaction with natural killer (NK) cells, and the effects of this interaction
      on NK cell phenotypic characteristics and functional activities. METHODS: DPMSCs
      isolated from the decidua parietalis of human fetal membranes were cultured with
      interleukin (IL)-2-activated and IL-2-unactivated NK cells isolated from healthy
      human peripheral blood. NK cell proliferation and cytolytic activities were then
      examined using functional assays. NK cell expression of receptors mediating the
      cytolytic activity against DPMSCs, and the mechanism underlying this effect on
      DPMSCs, were also examined using flow cytometry and light microscopy,
      respectively. RESULTS: DPMSCs stimulated IL-2-induced proliferation of resting NK
      cells and the proliferation of activated NK cells. Moreover, IL-2-activated NK
      cells, but not freshly isolated NK cells, efficiently lysed DPMSCs. The induction
      of this NK cell cytolytic activity against DPMSCs was mediated by the activating
      NK cell receptors NKG2D, CD69, NKp30, and NKp44. However, DPMSCs showed a direct
      induction of NK cell cytolytic activity through CD69. We also found that DPMSCs
      expressed the ligands for these activating NK cell receptors including Nectin-2,
      ULBP-2, MICA, and MICB. Although DPMSCs expressed HLA class I molecules, they
      were susceptible to lysis by NK cells, suggesting that HLA class I antigens do
      not play a significant role in NK cell cytolytic action. In addition, DPMSCs did
      not inhibit NK cell cytolytic activity against cancer cells. Importantly, DPMSCs
      significantly increased NK expression of inflammatory molecules with anticancer
      activities. CONCLUSIONS: We conclude that DPMSCs have potential for therapeutic
      application in cancer therapy, but not in transplantation or immunological
      diseases.

PMID- 29650046
TI  - Blighted ovum and tubal pregnancy: a rare form of heterotopic pregnancy: case
      report.
AB  - BACKGROUND: Heterotopic pregnancies are rare in spontaneous conceptions.
      Nonetheless, when it does occur, the intrauterine pregnancy is usually viable. We
      herein present a true rarity of the coexistence of a blighted ovum and an ectopic
      pregnancy. CASE PRESENTATION: A 25 year old G2P1001 married seamstress of African
      ethnicity at 8 weeks of amenorrhoea presented to our health facility with a 4 day
      history of lower abdominal pains and vaginal bleeding for which physical
      examination revealed a closed cervix. Trans-abdominal ultrasound scan confirmed a
      diagnosis of a blighted ovum and an ectopic pregnancy. Patient was managed with
      surgical therapy. Evolution thereafter was uneventful. CONCLUSION: The case
      presented confirms that HP can occur in the absence of predisposing factors, and
      that the detection of a blighted ovum should not preclude the possibility of a
      simultaneous ectopic pregnancy. A high index of suspicion could lead to early
      diagnosis, prompt management and a favourable prognosis even in a low-income
      setting.

PMID- 29650047
TI  - Care Cascade for targeted tuberculosis testing and linkage to Care in Homeless
      Populations in the United States: a meta-analysis.
AB  - BACKGROUND: Homelessness increases the risk of tuberculosis (TB) disease and
      latent TB infection (LTBI), but persons experiencing homelessness often lack
      access to testing and treatment. We assessed the yield of TB testing and linkage
      to care for programs targeting homeless populations in the United States.
      METHODS: We conducted a comprehensive search of peer-reviewed and grey
      literature, adapting Cochrane systematic review methods. Two reviewers
      independently assessed study eligibility and abstracted key data on the testing
      to care cascade: number of persons reached, recruited for testing, tested for
      LTBI, with valid test results, referred to follow-up care, and initiating care.
      We used random effects to calculate pooled proportions and 95% confidence
      intervals (CI) of persons retained in each step via inverse-variance weighted
      meta-analysis, and cumulative proportions as products of adjacent step
      proportions. RESULTS: We identified 23 studies published between 1986 and 2014,
      conducted in 12 states and 15 cities. Among studies using tuberculin skin tests
      (TST) we found that 93.7% (CI 72.4-100%) of persons reached were recruited, 97.9%
      (89.3-100%) of those recruited had tests placed, 85.5% (78.6-91.3%) of those with
      tests placed returned for reading, 99.9% (99.6-100%) of those with tests read had
      valid results, and 24.7% (21.0-28.5%) with valid results tested positive. All
      persons testing positive were referred to follow-up care, and 99.8% attended at
      least one session of follow-up care. Heterogeneity was high for most pooled
      proportions. For a hypothetical cohort of 1000 persons experiencing homelessness
      reached by a targeted testing program using TST, an estimated 917 were tested,
      194 were positive, and all of these initiated follow-up care. CONCLUSIONS:
      Targeted TB testing of persons experiencing homelessness appears effective in
      detecting LTBI and connecting persons to care and potential treatment. Future
      evaluations should assess diagnostic use of interferon gamma release assays and
      completion of treatment, and costs of testing and treatment.

PMID- 29650048
TI  - A comparison of the stem cell characteristics of murine tenocytes and tendon
      derived stem cells.
AB  - Tendon is a commonly injured soft musculoskeletal tissue, however, poor healing
      potential and ineffective treatment strategies result in persistent injuries and
      tissue that is unable to perform its normal physiological function. The
      identification of a stem cell population within tendon tissue holds therapeutic
      potential for treatment of tendon injuries. This study aimed, for the first time,
      to characterise and compare tenocyte and tendon-derived stem cell (TDSC)
      populations in murine tendon. Tenocytes and TDSCs were isolated from murine tail
      tendon. The cells were characterised for morphology, clonogenicity,
      proliferation, stem cell and tenogenic marker expression and multipotency. TDSCs
      demonstrated a rounded morphology, compared with a more fibroblastic morphology
      for tenocytes. Tenocytes had greater clonogenic potential and a smaller
      population doubling time compared with TDSCs. Stem cell and early tenogenic
      markers were more highly expressed in TDSCs, whereas late tenogenic markers were
      more highly expressed in tenocytes. Multipotency was increased in TDSCs with the
      presence of adipogenic differentiation which was absent in tenocytes. The
      differences in morphology, clonogenicity, stem cell marker expression and
      multipotency observed between tenocytes and TDSCs indicate that at least two cell
      populations are present in murine tail tendon. Determination of the most
      effective cell population for tendon repair is required in future studies, which
      in turn may aid in tendon repair strategies.

PMID- 29650050
TI  - The associations of comorbidities and consumption of fruit and vegetable with
      quality of life among stomach cancer survivors.
AB  - BACKGROUND: Stomach cancer survivors (SCS) often carry the dual burden of the
      cancer itself and other comorbidities; meanwhile, they are highly motivated to
      seek health advice about lifestyles to improve their health and quality of life
      (QOL). The associations of the comorbidity and the consumption of vegetable and
      fruit with QOL remain even less clear among the SCS. This study aimed to
      investigate the associations of comorbidities and consumption of fruit and
      vegetable with QOL among SCS. METHODS: A cross-sectional study was conducted
      among 969 SCS between April and July 2015 in Shanghai, People's Republic of
      China. Data were collected using a self-reported questionnaire, which included
      questions on sociodemographic characteristics, comorbidities and fruit and
      vegetable consumption, and a simplified Chinese version of the European
      Organization for Research and Treatment quality of life version 3 (EORTC QLQ-C30)
      questionnaire. In order to mitigate the bias caused by confounding factors,
      multiple linear regression models were employed to calculate the adjusted means
      of QOL scores. RESULTS: The proportion of participants without any comorbidity
      was only 23.3%, and the most common comorbidity among SCS was digestive diseases
      (49.8%). Participants with comorbidity generally reported lower scores for global
      health and functioning subscales and higher scores for symptom in EORTC QLQ-C30
      compared to participants without comorbidity, indicating poorer QOL. Higher
      scores in most functioning subscales and lower scores in some symptoms subscales
      were found in participants (38.7%) who ate more than 250 g vegetables every day,
      compared to participants with less vegetable consumption, and in participants
      (58.1%) who ate fruit every day, compared to participants who didn't eat fruit
      every day indicating better QOL. CONCLUSIONS: The comorbidities are common health
      problems among SCS and have significantly negative influence on QOL, and
      participants with comorbidities generally reported lower QOL scores. The enough
      vegetables and fruit consumption are positively associated with QOL of SCS. These
      findings suggested that a multidisciplinary team approach and a variety of
      delivery systems are needed to address the medical, psychosocial, and lifestyle
      components for enriching patient-centered care among SCS.

PMID- 29650051
TI  - Proteolytic biomarkers are related to prognosis in COPD- report from a population
      based cohort.
AB  - BACKGROUND: The imbalance between proteases and anti-proteases is considered to
      contribute to the development of COPD. Our aim was to evaluate the protease MMP
      9, the antiprotease TIMP-1 and the MMP-9/TIMP-1-ratio as biomarkers in relation
      to prognosis. Prognosis was assessed as lung function decline and mortality. This
      was done among subjects with COPD in a population-based cohort. METHODS: In 2005,
      clinical examinations including spirometry and peripheral blood sampling, were
      made in a longitudinal population-based cohort. In total, 1542 individuals
      participated, whereof 594 with COPD. In 2010, 1031 subjects participated in
      clinical examinations, and 952 subjects underwent spirometry in both 2005 and
      2010. Serum MMP-9 and TIMP-1 concentrations were measured with enzyme linked
      immunosorbent assay (ELISA). Mortality data were collected from the Swedish
      national mortality register from the date of examination in 2005 until 31st
      December 2010. RESULTS: The correlation between biomarkers and lung function
      decline was similar in non-COPD and COPD, but only significant for MMP-9 and MMP
      9/TIMP-1-ratio in non-COPD. Mortality was higher in COPD than non-COPD (16% vs.
      10%, p = 0.008). MMP-9 concentrations and MMP-9/TIMP-1 ratios in 2005 were higher
      among those who died during follow up, as well as among those alive but not
      participating in 2010, when compared to those participating in the 2010
      examination. In non-COPD, male sex, age, burden of smoking, heart disease and MMP
      9/TIMP-1 ratio were associated with increased risk for death, while increased
      TIMP-1 was protective. Among those with COPD, age, current smoking, increased MMP
      9 and MMP-9/TIMP-1 ratio were associated with an increased risk for death.
      CONCLUSIONS: The expected association between these biomarkers and lung function
      decline in COPD was not confirmed in this population-based study, probably due to
      a healthy survivor effect. Still, it is suggested that increased proteolytic
      imbalance may be of greater prognostic importance in COPD than in non-COPD.

PMID- 29650052
TI  - Weighting of orthostatic intolerance time measurements with standing difficulty
      score stratifies ME/CFS symptom severity and analyte detection.
AB  - BACKGROUND: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is
      clinically defined and characterised by persistent disabling tiredness and
      exertional malaise, leading to functional impairment. METHODS: This study
      introduces the weighted standing time (WST) as a proxy for ME/CFS severity, and
      investigates its behaviour in an Australian cohort. WST was calculated from
      standing time and subjective standing difficulty data, collected via orthostatic
      intolerance assessments. The distribution of WST for healthy controls and ME/CFS
      patients was correlated with the clinical criteria, as well as pathology and
      cytokine markers. Included in the WST cytokine analyses were activins A and B,
      cytokines causally linked to inflammation, and previously demonstrated to
      separate ME/CFS from healthy controls. Forty-five ME/CFS patients were recruited
      from the CFS Discovery Clinic (Victoria) between 2011 and 2013. Seventeen healthy
      controls were recruited concurrently and identically assessed. RESULTS: WST
      distribution was significantly different between ME/CFS participants and
      controls, with six diagnostic criteria, five analytes and one cytokine also
      significantly different when comparing severity via WST. On direct comparison of
      ME/CFS to study controls, only serum activin B was significantly elevated, with
      no significant variation observed for a broad range of serum and urine markers,
      or other serum cytokines. CONCLUSIONS: The enhanced understanding of standing
      test behaviour to reflect orthostatic intolerance as a ME/CFS symptom, and the
      subsequent calculation of WST, will encourage the greater implementation of this
      simple test as a measure of ME/CFS diagnosis, and symptom severity, to the
      benefit of improved diagnosis and guidance for potential treatments.

PMID- 29650053
TI  - Volume of mural thrombus plays a role in the elevation of inflammatory markers
      after endovascular aortic repair.
AB  - BACKGROUND: Although systemic inflammatory responses are common after
      endovascular aortic repair (EVAR), its etiology remains uncertain. It is normally
      well tolerated and has a benign course. This study was undertaken to investigate
      the possible etiology of post-EVAR inflammation by measuring volumes of chronic
      mural thrombus and fresh thrombus. METHODS: The subjects of this study included
      34 patients who underwent EVAR from February 2012 to July 2017. Inflammatory
      markers in all the patients were evaluated before surgery, using the highest
      value among the laboratory data up to 5 days after surgery, and postoperative
      computed tomographic angiography (CTA) was taken for all of them before their
      discharging. Volumes of mural thrombus and fresh thrombus were calculated by CTA.
      The mean interval from surgery to immediate postoperative CTA was estimated as
      6.8 +/- 4.0 days. RESULTS: After undergoing EVAR, white blood cell (WBC) (p <
      0.01), C-reactive protein (CRP) (p < 0.01) and erythrocyte sedimentation rate
      (ESR) (p = 0.01) were significantly elevated. Two groups were defined according
      to the post-implantation syndrome (PIS) by the criteria of systemic inflammatory
      response syndrome (SIRS);no significant differences were observed in any factors
      between the two groups. Classification of two groups by the criteria of
      increasing WBC and CRP revealed that inflammatory markers were significantly
      enhanced as the volume of mural thrombus increased (p = 0.03). However, no
      significant risk factor was found in view of aneurysmal growth after EVAR.
      CONCLUSION: Volume of mural thrombus is an important risk factor for the
      elevation of inflammatory markers after EVAR.

PMID- 29650054
TI  - Global commitments and China's endeavors to promote health and achieve
      sustainable development goals.
AB  - BACKGROUND: With its immense population and as the largest developing country in
      the world, China has made remarkable achievements in health promotion at a
      relatively low cost. However, China is still faced with challenges such as
      changes of disease spectrum, the coming era of an aging society, and the risk of
      environmental pollution. MAIN TEXT: On October 25, 2016, China formally passed
      the blueprint of "Healthy China 2030," working towards the national goal of
      reaching a health standard on par with developed countries by 2030, which was
      also a response to realize the 2030 United Nations Sustainable Development Goals.
      "Healthy China 2030" is comprised of 29 chapters that cover five health areas.
      China is sparing no effort to transfer from being merely the most populous
      country, to becoming a leading nation in health education. In "Healthy China
      2030," collaborated construction and resource sharing were clearly stated as the
      core strategy. A shift in concentration towards coordinated development of health
      based economy from a previous pursuit of rapid economic growth was also
      underlined. There are also several major issues, such as severely aging
      population, the burden of chronic diseases, the insufficiency of health
      expenditure, and the great demand on health protection, waiting to be dealt with
      during the implementation process of "Healthy China 2030". CONCLUSIONS: "Healthy
      China 2030" is a momentous move to enhance public health, which is also a
      response to the global commitments. We also need to rethink our approach to reach
      the living standards and maintain a better environment.

PMID- 29650057
TI  - Blood money: Harvey's De motu cordis (1628) as an exercise in accounting.
AB  - William Harvey's famous quantitative argument from De motu cordis (1628) about
      the circulation of blood explained how a small amount of blood could recirculate
      and nourish the entire body, upending the Galenic conception of the blood's
      motion. This paper argues that the quantitative argument drew on the calculative
      and rhetorical skills of merchants, including Harvey's own brothers. Modern
      translations of De motu cordis obscure the language of accountancy that Harvey
      himself used. Like a merchant accounting for credits and debits, intake and
      output, goods and moneys, Harvey treated venous and arterial blood as essentially
      commensurate, quantifiable and fungible. For Harvey, the circulation (and
      recirculation) of blood was an arithmetical necessity. The development of
      Harvey's circulatory model followed shifts in the epistemic value of mercantile
      forms of knowledge, including accounting and arithmetic, also drawing on an
      Aristotelian language of reciprocity and balance that Harvey shared with
      mercantile advisers to the royal court. This paper places Harvey's calculations
      in a previously underappreciated context of economic crisis, whose debates
      focused largely on questions of circulation.

PMID- 29650055
TI  - A combined effort to avoid strongyle infection in horses in an oceanic climate
      region: rotational grazing and parasiticidal fungi.
AB  - BACKGROUND: An approach to preventing strongyle infection in horses was tested,
      comprising rotational pasturing and the administration of spores of two
      parasiticidal fungi, Mucor circinelloides and Duddingtonia flagrans. METHODS:
      Twenty-two adult Spanish Sport Horses were dewormed with ivermectin (1 mg pour
      on/kg body weight) and then randomly divided into three groups. G-1 was
      maintained with continuous grazing, and G-2 and G-3 were kept on a four-paddock
      rotation system. Commercial pelleted feed (2.5 kg/horse) was supplied to G-1 and
      G-2 twice a week; horses in G-3 received pellets containing 2 * 106 spores/kg of
      each fungus. Fecal samples were analyzed by the flotation method to estimate the
      reduction in the fecal egg counts (FECR), the percentage of horses shedding eggs
      (PHR), and the egg reappearance period (ERP). RESULTS: Third-stage larvae were
      identified in fecal pats as Cyathostomum (sensu lato) types A, C and D,
      Gyalocephalus capitatus, Triodontophorus serratus, Poteriosthomum spp.,
      Strongylus vulgaris and S. edentatus. Two weeks after treatment, the FECR values
      were 100% in G-1, 96% in G-2 and 99% in G-3; the PHR values were 100% in G-1, 75%
      in G-2 and 88% in G-3. A strongyle ERP of 6 weeks was observed in G-1, ERP of 10
      weeks was observed in G-2, and ERP of 16 weeks was observed in G-3. The counts of
      eggs per gram of feces (EPG) were > 300 EPG in G-1 and G-2 but remained below 250
      EPG in G-3 throughout the observation period of 12 months. CONCLUSIONS: These
      results suggest that horse strongyle infection could be decreased by combining
      rotational pasturing with feeding pellets containing the spores of parasiticidal
      fungi.

PMID- 29650056
TI  - Pancreatoduodenectomy with or without prophylactic falciform ligament wrap around
      the gastroduodenal artery stump for prevention of pancreatectomy hemorrhage.
AB  - BACKGROUND: The purpose of this study is to evaluate whether wrapping of the
      pedicled falciform ligamentum flap around the gastroduodenal artery (GDA)
      stump/hepatic artery can significantly decrease the incidence of erosion
      hemorrhage after pancreatoduodenectomy (PD). METHODS/DESIGN: This is a randomized
      controlled multicenter trial involving 400 patients undergoing PD. Patients will
      be randomized into two groups. The intervention group consists of 200 patients
      with a prophylactic wrapping of the GDA stump using the pedicled falciform
      ligament. The control group consists of 200 patients without the wrap. The
      primary endpoint is the rate of postoperative erosion hemorrhage of the GDA stump
      or hepatic artery within 3 months. The secondary endpoints are postpancreatectomy
      hemorrhage stratified according to the texture of the pancreas, postoperative
      pancreatic fistula (POPF), postoperative rate of therapeutic interventions,
      morbidity, and mortality. DISCUSSION: Only few retrospective studies investigated
      the effectiveness of a falciform ligament wrap around the GDA for prevention of
      erosion hemorrhage. Erosion hemorrhage occurs in up to 6-9% of cases after PD and
      is most frequently evoked by a POPF. Erosion hemorrhage is associated with a
      remarkable mortality of over 30%. The rate of hemorrhage after performing the
      wrap is reported to be low. However, there exist no prospectively controlled data
      to support its general use. Therefore, the presented randomized controlled trial
      will provide clinically relevant evidence of the effectiveness of the wrap with
      statistical significance. TRIAL REGISTRATION: clinicaltrials.gov, NCT02588066 ;
      Registered on 27 October 2015.

PMID- 29650049
TI  - Variation in general supportive and preventive intensive care management of
      traumatic brain injury: a survey in 66 neurotrauma centers participating in the
      Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain
      Injury (CENTER-TBI) study.
AB  - BACKGROUND: General supportive and preventive measures in the intensive care
      management of traumatic brain injury (TBI) aim to prevent or limit secondary
      brain injury and optimize recovery. The aim of this survey was to assess and
      quantify variation in perceptions on intensive care unit (ICU) management of
      patients with TBI in European neurotrauma centers. METHODS: We performed a survey
      as part of the Collaborative European NeuroTrauma Effectiveness Research in
      Traumatic Brain Injury (CENTER-TBI) study. We analyzed 23 questions focused on:
      1) circulatory and respiratory management; 2) fever control; 3) use of
      corticosteroids; 4) nutrition and glucose management; and 5) seizure prophylaxis
      and treatment. RESULTS: The survey was completed predominantly by intensivists (n
      = 33, 50%) and neurosurgeons (n = 23, 35%) from 66 centers (97% response rate).
      The most common cerebral perfusion pressure (CPP) target was > 60 mmHg (n = 39,
      60%) and/or an individualized target (n = 25, 38%). To support CPP, crystalloid
      fluid loading (n = 60, 91%) was generally preferred over albumin (n = 15, 23%),
      and vasopressors (n = 63, 96%) over inotropes (n = 29, 44%). The most commonly
      reported target of partial pressure of carbon dioxide in arterial blood (PaCO2)
      was 36-40 mmHg (4.8-5.3 kPa) in case of controlled intracranial pressure (ICP) <
      20 mmHg (n = 45, 69%) and PaCO2 target of 30-35 mmHg (4-4.7 kPa) in case of
      raised ICP (n = 40, 62%). Almost all respondents indicated to generally treat
      fever (n = 65, 98%) with paracetamol (n = 61, 92%) and/or external cooling (n =
      49, 74%). Conventional glucose management (n = 43, 66%) was preferred over tight
      glycemic control (n = 18, 28%). More than half of the respondents indicated to
      aim for full caloric replacement within 7 days (n = 43, 66%) using enteral
      nutrition (n = 60, 92%). Indications for and duration of seizure prophylaxis
      varied, and levetiracetam was mostly reported as the agent of choice for both
      seizure prophylaxis (n = 32, 49%) and treatment (n = 40, 61%). CONCLUSIONS:
      Practice preferences vary substantially regarding general supportive and
      preventive measures in TBI patients at ICUs of European neurotrauma centers.
      These results provide an opportunity for future comparative effectiveness
      research, since a more evidence-based uniformity in good practices in general ICU
      management could have a major impact on TBI outcome.

PMID- 29650058
TI  - Roles of instrumented farm-scale trials in trade-off assessments of pasture-based
      ruminant production systems.
AB  - For livestock production systems to play a positive role in global food security,
      the balance between their benefits and disbenefits to society must be
      appropriately managed. Based on the evidence provided by field-scale randomised
      controlled trials around the world, this debate has traditionally centred on the
      concept of economic-environmental trade-offs, of which existence is theoretically
      assured when resource allocation is perfect on the farm. Recent research
      conducted on commercial farms indicates, however, that the economic-environmental
      nexus is not nearly as straightforward in the real world, with environmental
      performances of enterprises often positively correlated with their economic
      profitability. Using high-resolution primary data from the North Wyke Farm
      Platform, an intensively instrumented farm-scale ruminant research facility
      located in southwest United Kingdom, this paper proposes a novel, information
      driven approach to carry out comprehensive assessments of economic-environmental
      trade-offs inherent within pasture-based cattle and sheep production systems. The
      results of a data-mining exercise suggest that a potentially systematic
      interaction exists between 'soil health', ecological surroundings and livestock
      grazing, whereby a higher level of soil organic carbon (SOC) stock is associated
      with a better animal performance and less nutrient losses into watercourses, and
      a higher stocking density with greater botanical diversity and elevated SOC. We
      contend that a combination of farming system-wide trials and environmental
      instrumentation provides an ideal setting for enrolling scientifically sound and
      biologically informative metrics for agricultural sustainability, through which
      agricultural producers could obtain guidance to manage soils, water, pasture and
      livestock in an economically and environmentally acceptable manner. Priority
      areas for future farm-scale research to ensure long-term sustainability are also
      discussed.

PMID- 29650059
TI  - Labyrinthitis Ossificans in a Cynomolgus Macaque (Macaca fascicularis).
AB  - Labyrinthitis is inflammation of the membranous and bony labyrinth of the inner
      ear. Typical portals of entry includehematogenous spread from the cochlear
      vasculature, passage of otitis media pathogens through the round window, and
      mostcommonly, meningogenic spread from the subarachnoid space. The sequela of
      chronic inner ear inflammation is labyrinthitisossificans, in which inner ear
      structures are replaced by fibrous and osseous tissues. Labyrinthitis in humans
      has been reportedconcurrently with infection due to various viruses (for example,
      varicella-zoster, measles, mumps) and bacteria (for example,Treponema pallidum,
      Streptococcus pneumoniae) and may be associated with vertebrobasilar ischemia and
      meningitis. Profoundsensorineural hearing loss is a common, serious complication
      of this disease. Here, we report a case of labyrinthitisossificans in a
      cynomolgus macaque (Macaca fascicularis) with a potential infectious etiology.
      Historically, this animal hadan indwelling femoral intravenous catheter for more
      than 4 y. He presented with a right-sided head tilt and incoordinationof 2 mo
      duration. The macaque was treated with NSAID and antibiotics, which corrected the
      incoordination but not the headtilt. MRI revealed right-sided labyrinthitis, and
      euthanasia was elected due to clinical signs that were refractory to
      treatment.Gross pathology was unremarkable, but histopathology revealed chronic
      labyrinthitis ossificans with local fibroplasia andvestibuloauditory neuritis. We
      describe here the clinical features, imaging, and histologic lesions of
      labyrinthitis in a macaque.

PMID- 29650061
TI  - Comparison of sperm motility subpopulation structure among wild anadromous and
      farmed male Atlantic salmon (Salmo salar) parr using a CASA system.
AB  - Atlantic salmon (Salmo salar) is an endangered freshwater species that needs help
      to recover its wild stocks. However, the priority in aquaculture is to obtain
      successful fertilisation and genetic variability to secure the revival of the
      species. The aims of the present work were to study sperm subpopulation structure
      and motility patterns in wild anadromous males and farmed male Atlantic salmon
      parr. Salmon sperm samples were collected from wild anadromous salmon (WS) and
      two generations of farmed parr males. Sperm samples were collected from sexually
      mature males and sperm motility was analysed at different times after activation
      (5 and 35s). Differences among the three groups were analysed using statistical
      techniques based on Cluster analysis the Bayesian method. Atlantic salmon were
      found to have three sperm subpopulations, and the spermatozoa in ejaculates of
      mature farmed parr males had a higher velocity and larger size than those of WS
      males. This could be an adaptation to high sperm competition because salmonid
      species are naturally adapted to this process. Motility analysis enables us to
      identify sperm subpopulations, and it may be useful to correlate these sperm
      subpopulations with fertilisation ability to test whether faster-swimming
      spermatozoa have a higher probability of success.

PMID- 29650060
TI  - Gastrostomy versus nasogastric tube feeding for chemoradiation patients with head
      and neck cancer: the TUBE pilot RCT.
AB  - BACKGROUND: Approximately 9000 new cases of head and neck squamous cell cancers
      (HNSCCs) are treated by the NHS each year. Chemoradiation therapy (CRT) is a
      commonly used treatment for advanced HNSCC. Approximately 90% of patients
      undergoing CRT require nutritional support via gastrostomy or nasogastric tube
      feeding. Long-term dysphagia following CRT is a primary concern for patients. The
      effect of enteral feeding routes on swallowing function is not well understood,
      and the two feeding methods have, to date (at the time of writing), not been
      compared. The aim of this pilot randomised controlled trial (RCT) was to compare
      these two options. METHODS: This was a mixed-methods multicentre study to
      establish the feasibility of a RCT comparing oral feeding plus pre-treatment
      gastrostomy with oral feeding plus as-required nasogastric tube feeding in
      patients with HNSCC. Patients were recruited from four tertiary centres treating
      cancer and randomised to the two arms of the study (using a 1 : 1 ratio). The
      eligibility criteria were patients with advanced-staged HNSCC who were suitable
      for primary CRT with curative intent and who presented with no swallowing
      problems. MAIN OUTCOME MEASURES: The primary outcome was the willingness to be
      randomised. A qualitative process evaluation was conducted alongside an economic
      modelling exercise. The criteria for progression to a Phase III trial were based
      on a hypothesised recruitment rate of at least 50%, collection of outcome
      measures in at least 80% of those recruited and an economic value-of-information
      analysis for cost-effectiveness. RESULTS: Of the 75 patients approached about the
      trial, only 17 consented to be randomised [0.23, 95% confidence interval (CI)
      0.13 to 0.32]. Among those who were randomised, the compliance rate was high
      (0.94, 95% CI 0.83 to 1.05). Retention rates were high at completion of treatment
      (0.94, 95% CI 0.83 to 1.05), at the 3-month follow-up (0.88, 95% CI 0.73 to 1.04)
      and at the 6-month follow-up (0.88, 95% CI 0.73 to 1.04). No serious adverse
      events were recorded in relation to the trial. The qualitative substudy
      identified several factors that had an impact on recruitment, many of which are
      amenable to change. These included organisational factors, changing cancer
      treatments and patient and clinician preferences. A key reason for the
      differential recruitment between sites was the degree to which the
      multidisciplinary team gave a consistent demonstration of equipoise at all
      patient interactions at which supplementary feeding was discussed. An exploratory
      economic model generated from published evidence and expert opinion suggests
      that, over the 6-month model time horizon, pre-treatment gastrostomy tube feeding
      is not a cost-effective option, although this should be interpreted with caution
      and we recommend that this should not form the basis for policy. The economic
      value-of-information analysis indicates that additional research to eliminate
      uncertainty around model parameters is highly likely to be cost-effective. STUDY
      LIMITATIONS: The recruitment issues identified for this cohort may not be
      applicable to other populations undergoing CRT. There remains substantial
      uncertainty in the economic evaluation. CONCLUSIONS: The trial did not meet one
      of the three criteria for progression, as the recruitment rate was lower than
      hypothesised. Once patients were recruited to the trial, compliance and retention
      in the trial were both high. The implementation of organisational and operational
      measures can increase the numbers recruited. The economic analysis suggests that
      further research in this area is likely to be cost-effective. FUTURE WORK: The
      implementation of organisational and operational measures can increase
      recruitment. The appropriate research question and design of a future study needs
      to be identified. More work is needed to understand the experiences of
      nasogastric tube feeding in patients undergoing CRT. TRIAL REGISTRATION: Current
      Controlled Trials ISRCTN48569216. 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. 22,
      No. 16. See the NIHR Journals Library website for further project information.

PMID- 29650062
TI  - Fish sperm motility analysis: the central role of the flagellum.
AB  - Motility analysis of spermatozoa relies on the investigation of either head
      trajectories or flagellum characteristics. Those two sets of parameters are far
      from being independent, the flagellum playing the role of motor, whereas the head
      plays a passive role of cargo. Therefore, quantitative descriptions of head
      trajectories represent a simplification of the complex pattern of whole sperm
      cell motion, resulting from the waves developed by the flagellum. The flagellum
      itself responds to a large variety of signals that precisely control its axoneme
      to allow activation, acceleration, slowing down or reorientation of the whole
      spermatozoon. Thus, it is obvious that analysis of flagellum characteristics
      provides information on the original source of movement and orientation of the
      sperm cell and presents additional parameters that enrich the panoply of
      quantitative descriptors of sperm motility. In this review, we briefly describe
      the methodologies used to obtain good-quality images of fish spermatozoa (head
      and especially flagellum) while they move fast and the methods developed for
      their analysis. The paper also aims to establish a link between classical
      analyses by computer-aided sperm analysis (CASA) and the descriptors generated by
      fish sperm flagellum analysis, and emphasises the information to be gained
      regarding motility performance from flagellum motion data.

PMID- 29650063
TI  - The Enduring Value of the Physical Examination.
AB  - This article focuses exclusively on physical examination (PE) in the context of
      clinical medicine, that is, the interaction between a health care provider and
      patient. In essence, there is not only benefit (value) to PE but also that it
      will last (endure) for some time. Both "enduring" and "value" are explored in
      more depth with respect to the future integration of PE into the clinical
      assessment of a patient and how its value extends well beyond current
      diagnostic/cost-based metrics.

PMID- 29650064
TI  - The Physical Examination as Ritual: Social Sciences and Embodiment in the Context
      of the Physical Examination.
AB  - The privilege of examining a patient is a skill of value beyond its diagnostic
      utility. A thorough physical examination is an important ritual that benefits
      patients and physicians. The concept of embodiment helps one understand how
      illness and pain further define and shape the lived experiences of individuals in
      the context of their race, gender, sexuality, and socioeconomic status.
      Understanding ritual in medicine, including the placebo effects of such rituals,
      reaffirms the centrality of the physical examination to the process of building
      strong physician-patient relationships.

PMID- 29650065
TI  - The Hypothesis-Driven Physical Examination.
AB  - The physical examination remains a vital part of the clinical encounter. However,
      physical examination skills have declined in recent years, in part because of
      decreased time at the bedside. Many clinicians question the relevance of physical
      examinations in the age of technology. A hypothesis-driven approach to teaching
      and practicing the physical examination emphasizes the performance of maneuvers
      that can alter the likelihood of disease. Likelihood ratios are diagnostic
      weights that allow clinicians to estimate the post-probability of disease. This
      hypothesis-driven approach to the physical examination increases its value and
      efficiency, while preserving its cultural role in the patient-physician
      relationship.

PMID- 29650066
TI  - The Role of Technology in the Bedside Encounter.
AB  - Technology has the potential to both distract and reconnect providers with their
      patients. The widespread adoption of electronic medical records in recent years
      pulls physicians away from time at the bedside. However, when used in conjunction
      with patients, technology has the potential to bring patients and physicians
      together. The increasing use of point-of-care ultrasound by physicians is
      changing the bedside encounter by allowing for real-time diagnosis with the
      treating physician. It is a powerful example of the way technology can be a force
      for refocusing on the bedside encounter.

PMID- 29650067
TI  - Diagnostic Errors and the Bedside Clinical Examination.
AB  - Diagnostic errors are common in clinical practice and lead to adverse patient
      outcomes. Systematic reviews have shown that inadequate history taking and
      physical examination lead to a plurality, if not a majority, of diagnostic
      errors. Recent advances in cognitive science have also shown that unconscious
      biases likely contribute to many diagnostic errors. Research into diagnostic
      error has been hampered by methodologic inconsistency and a paucity of studies in
      real-world clinical settings. The best evidence indicates that educational
      interventions to reduce diagnostic error should give physicians feedback about
      clinical outcomes and enhance their ability to recognize signs and symptoms of
      specific diseases at the bedside.

PMID- 29650068
TI  - The Outpatient Physical Examination.
AB  - The physical examination in the outpatient setting is a valuable tool. Even in
      settings where there is lack of evidence, such as the annual physical examination
      of an asymptomatic adult, the physical examination is beneficial for the
      physician-patient relationship. When a patient has specific symptoms, the
      physical examination-in addition to a thorough history-can help narrow down, or
      in many cases establish, a diagnosis. In a time where imaging and laboratory
      tests are easily available, but are expensive and can be invasive, a skilled
      physical examination remains an important component of patient evaluation.

PMID- 29650069
TI  - The Electronic Health Record and the Clinical Examination.
AB  - This review examines how the adoption of the electronic health record (EHR) has
      changed the most fundamental unit of medicine: the clinical examination. The
      impact of the EHR on the clinical history, physical examination, documentation,
      and the doctor-patient relationship is described. The EHR now has a dominant role
      in clinical care and will be a central factor in clinical work of the future.
      Conversation needs to be shifted toward defining best practices with current EHRs
      inside and outside of the examination room.

PMID- 29650070
TI  - Communication and Ethics in the Clinical Examination.
AB  - At the heart of every effective patient-physician interaction is a relationship
      that is built on trust. Cultivating sound communication skills coupled with the
      awareness and application of ethical principles is integral to this process. One
      of the foremost challenges in competent practice is negotiating situations that
      arise at the bedside when such issues as patient autonomy, differing world views,
      honesty, and cost stewardship come into conflict. It is essential for health care
      providers to consider how to detect and prioritize these issues as they advocate
      for high-quality and patient-centered care.

PMID- 29650071
TI  - Improving Observational Skills to Enhance the Clinical Examination.
AB  - For much of the 20th century, educators lacked evidence that teaching
      observational skills could benefit modern medicine. But in 2001, a statistical
      model emerged that supported the effectiveness of teaching observational skills
      to medical students using a museum-based curriculum. The story that led to that
      ground-breaking study, and the consequences that sprung from it, is retold here,
      traveling from the darkened caves in the foothills of France to the brightly lit
      galleries of the Yale center for British art. It never would have happened
      without the indelible mark made by one curious man's journey.

PMID- 29650072
TI  - Patient-Centered Bedside Rounds and the Clinical Examination.
AB  - Bedside hospital rounds promote patient-centered care in teaching and nonteaching
      settings. Patients and families prefer bedside rounds and provider acceptance is
      increasing. Efficient bedside rounds with an interprofessional team or with
      learners requires preparation of the patient and the rounding team. Bedside
      "choreography" provides structure and sets expectations for time spent in the
      room. By using relationship-centered communication, rounds can be both patient
      proximate and patient centered. The clinical examination can be integrated into
      the flow of the presentation and case discussion. Patient and provider experience
      can be enhanced through investing time at the bedside.

PMID- 29650073
TI  - The Clinical Examination and Socially At-Risk Populations: The Examination
      Matters for Health Disparities.
AB  - Data from the United States show that persons from low socioeconomic backgrounds,
      those who are socially isolated, belong to racial or ethnic minority groups, or
      identify as lesbian, gay, bisexual, or transgender experience health disparities
      at a higher rate. Clinicians must transition from a biomedical to a
      biopsychosocial framework within the clinical examination to better address
      social determinants of health that contribute to health disparities. We review
      the characteristics of successful patient-clinician interactions. We describe
      strategies for relationship-centered care within routine encounters. Our goal is
      to train clinicians to mitigate differences and reduce disparities in health care
      delivery.

PMID- 29650074
TI  - Clinical Examination Component of Telemedicine, Telehealth, mHealth, and
      Connected Health Medical Practices.
AB  - Telemedicine and telehealth are the practices of medicine at a distance.
      Performing the equivalent of a complete clinical examination by telemedicine
      would be unusual. However, components of a more traditional clinical examination
      are part of the telemedicine workup for specific conditions. Telemedicine
      clinical examinations are facilitated, and enhanced, through the integration of a
      class of medical devices referred to as telemedicine peripherals (eg, electronic
      stethoscopes, tele-ophthalmoscopes, video-otoscopes, and so forth). Direct-to
      consumer telehealth is a rapidly expanding segment of the health care service
      industry.

PMID- 29650075
TI  - Clinical Skills Assessment in the Twenty-First Century.
AB  - Clinical skills remain fundamental to the practice of medicine and form a core
      component of the professional identity of the physician. However, evidence exists
      to suggest that the practice of some clinical skills is declining, particularly
      in the United States. A decline in practice of any skill can lead to a decline in
      its teaching and assessment, with further decline in practice as a result.
      Consequently, assessment not only drives learning of clinical skills, but their
      practice. This article summarizes contemporary approaches to clinical skills
      assessment that, if more widely adopted, could support the maintenance and
      reinvigoration of bedside clinical skills.

PMID- 29650076
TI  - Digital Tools to Enhance Clinical Reasoning.
AB  - Physicians can improve their diagnostic acumen by adopting a simulation-based
      approach to analyzing published cases. The tight coupling of clinical problems
      and their solutions affords physicians the opportunity to efficiently upgrade
      their illness scripts (structured knowledge of a specific disease) and schemas
      (structured frameworks for common problems). The more times clinicians practice
      accessing and applying those knowledge structures through published cases, the
      greater the odds that they will have an enhanced approach to similar patient
      cases in the future. This article highlights digital resources that increase the
      number of cases a clinician experiences and learns from.

PMID- 29650077
TI  - Recapturing the Lost Art.

PMID- 29650078
TI  - The Clinical Examination in Twenty-First Century Medicine.

PMID- 29650079
TI  - Introduction.

PMID- 29650080
TI  - Definition, Classification and Diagnosis of Diabetes, Prediabetes and Metabolic
      Syndrome.

PMID- 29650081
TI  - Hypoglycemia.

PMID- 29650082
TI  - Hyperglycemic Emergencies in Adults.

PMID- 29650083
TI  - In-Hospital Management of Diabetes.

PMID- 29650084
TI  - Weight Management in Diabetes.

PMID- 29650085
TI  - Diabetes and Mental Health.

PMID- 29650086
TI  - Influenza, Pneumococcal, Hepatitis B and Herpes Zoster Vaccinations.

PMID- 29650087
TI  - Diabetes and Transplantation.

PMID- 29650088
TI  - Diabetes and Driving.

PMID- 29650089
TI  - Complementary and Alternative Medicine for Diabetes.

PMID- 29650090
TI  - Screening for Diabetes in Adults.

PMID- 29650091
TI  - Cardiovascular Protection in People With Diabetes.

PMID- 29650092
TI  - Screening for the Presence of Cardiovascular Disease.

PMID- 29650093
TI  - Dyslipidemia.

PMID- 29650094
TI  - Treatment of Hypertension.

PMID- 29650095
TI  - Management of Acute Coronary Syndromes.

PMID- 29650096
TI  - Treatment of Diabetes in People With Heart Failure.

PMID- 29650097
TI  - Reducing the Risk of Developing Diabetes.

PMID- 29650098
TI  - Chronic Kidney Disease in Diabetes.

PMID- 29650099
TI  - Retinopathy.

PMID- 29650100
TI  - Neuropathy.

PMID- 29650101
TI  - Foot Care.

PMID- 29650102
TI  - Sexual Dysfunction and Hypogonadism in Men With Diabetes.

PMID- 29650103
TI  - Type 1 Diabetes in Children and Adolescents.

PMID- 29650104
TI  - Type 2 Diabetes in Children and Adolescents.

PMID- 29650105
TI  - Diabetes and Pregnancy.

PMID- 29650106
TI  - Organization of Diabetes Care.

PMID- 29650107
TI  - Diabetes in Older People.

PMID- 29650108
TI  - Type 2 Diabetes and Indigenous Peoples.

PMID- 29650109
TI  - Self-Management Education and Support.

PMID- 29650110
TI  - Targets for Glycemic Control.

PMID- 29650111
TI  - Monitoring Glycemic Control.

PMID- 29650112
TI  - Physical Activity and Diabetes.

PMID- 29650113
TI  - Methods.

PMID- 29650114
TI  - Nutrition Therapy.

PMID- 29650115
TI  - Glycemic Management in Adults With Type 1 Diabetes.

PMID- 29650116
TI  - Pharmacologic Glycemic Management of Type 2 Diabetes in Adults.

PMID- 29650117
TI  - Implementation of Transcatheter Aortic Valve Replacement in France.
AB  - BACKGROUND: Transcatheter aortic valve replacement (TAVR) has emerged as an
      alternative to surgical aortic valve replacement (SAVR), but unbiased data
      regarding evolution of the treatment of patients with aortic stenosis at the
      nationwide level are scarce. OBJECTIVES: This study sought to evaluate the number
      of aortic valve replacements (AVRs) performed in France, changes over time, and
      the effect of the adoption of TAVR. METHODS: Based on a French administrative
      hospital-discharge database, the study collected all consecutive AVRs performed
      in France between 2007 and 2015. RESULTS: A total of 131,251 interventions were
      performed: 109,317 (83%) SAVR and 21,934 (17%) TAVR. AVR linearly increased (from
      10,892 to 18,704; p for trend <0.0001) mainly due to a marked increase in TAVR
      (from 244 to 6,722; p for trend = 0.0004), whereas SAVR remained stable (from
      10,892 to 11,982; p for trend = 0.18). Parallel to a decrease in the Charlson
      index (p for trend <0.05), SAVR and TAVR in-hospital mortality rates
      significantly declined (both p for trend <0.01). The number of TAVRs
      significantly increased in all age categories (<75, 75 to 79, 80 to 84, and >=85
      years of age; all p for trend = 0.003), but reached or even exceeded SAVR in the
      2 oldest categories. Although mortality rates declined for both isolated SAVR and
      TAVR, it became similar or slightly lower for TAVR than for isolated SAVR in 2015
      in the 3 oldest age categories even if it did not reach statistical significance
      (p = 0.66, p = 0.47, and p = 0.06, respectively). CONCLUSIONS: The number of AVRs
      markedly increased in France between 2007 and 2015 due to the wide adoption of
      TAVR, which represented one-third of all AVRs in 2015. Patients' profile
      improved, suggesting that patients are referred earlier, and in-hospital
      mortality declined in all AVR subsets. Despite a worse clinical profile, the
      immediate outcome of TAVR compared favorably to isolated SAVR in patients >75
      years of age. The results may have major implications for clinical practice and
      policymakers.

PMID- 29650118
TI  - Interpreting National Trends in Aortic Valve Replacement: Let the Buyer Beware.

PMID- 29650119
TI  - Assessing the Malignant Ventricular Arrhythmic Substrate in Patients With Brugada
      Syndrome.
AB  - BACKGROUND: Guidelines recommend the use of implanted cardioverter-defibrillators
      in patients with Brugada syndrome and induced ventricular tachyarrhythmias, but
      there is no evidence supporting it. OBJECTIVES: This prospective registry study
      was designed to explore clinical and electrophysiological predictors of malignant
      ventricular tachyarrhythmia inducibility in Brugada syndrome. METHODS: A total of
      191 consecutive selected patients with (group 1; n = 88) and without (group 2; n
      = 103) Brugada syndrome-related symptoms were prospectively enrolled in the
      registry. Patients underwent electrophysiological study and substrate mapping or
      ablation before and after ajmaline testing (1 mg/kg/5 min). RESULTS: Overall,
      before ajmaline testing, 53.4% of patients had ventricular tachyarrhythmia
      inducibility, which was more frequent in group 1 (65.9%) than in group 2 (42.7%;
      p < 0.001). Regardless of clinical presentation, larger substrates with more
      fragmented long-duration ventricular potentials were found in patients with
      inducible arrhythmias than in patients without inducible arrhythmias (p < 0.001).
      One extrastimulus was used in more extensive substrates (median 13 cm2; p <
      0.001), and ventricular fibrillation was the more frequently induced rhythm (p <
      0.001). After ajmaline, patients without arrhythmia inducibility had arrhythmia
      inducibility without a difference in substrate characteristics between the 2
      groups. The substrate size was the only independent predictor of inducibility
      (odds ratio: 4.51; 95% confidence interval: 2.51 to 8.09; p < 0.001). A substrate
      size of 4 cm2 best identified patients with inducible arrhythmias (area under the
      curve: 0.98; p < 0.001). Substrate ablation prevented ventricular tachyarrhythmia
      reinducibility. CONCLUSIONS: In Brugada syndrome dynamic substrate variability
      represents the pathophysiological basis of lethal ventricular tachyarrhythmias.
      Substrate size is independently associated with arrhythmia inducibility, and its
      determination after ajmaline identifies high-risk patients missed by clinical
      criteria. Substrate ablation is associated with electrocardiogram normalization
      and not arrhythmia reinducibility. (Epicardial Ablation in Brugada Syndrome
      [BRUGADA_I]; NCT02641431; Epicardial Ablation in Brugada Syndrome: An Extension
      Study of 200 BrS Patients; NCT03106701).

PMID- 29650120
TI  - Programmed Ventricular Stimulation and Brugada Syndrome: New Insights, Old
      Controversies.

PMID- 29650121
TI  - Prediction of Abnormal Myocardial Relaxation From Signal Processed Surface ECG.
AB  - BACKGROUND: Myocardial relaxation is impaired in almost all cases with left
      ventricular diastolic dysfunction (LVDD) and is a strong predictor of
      cardiovascular and all-cause mortality. OBJECTIVES: This study investigated the
      feasibility of signal-processed surface electrocardiography (spECG) as a
      diagnostic tool for predicting the presence of abnormal cardiac muscle
      relaxation. METHODS: A total of 188 outpatients referred for coronary computed
      tomography (CT) angiography underwent an echocardiogram for assessment of LVDD.
      The use of 12-lead spECG for predicting myocardial relaxation abnormalities as
      identified using tissue Doppler echocardiography was validated with machine
      learning approaches. RESULTS: A total of 188 subjects underwent diagnostic
      testing, with 133 (70%) showing abnormal myocardial relaxation on tissue Doppler
      imaging. A 12-lead spECG showed an area under the curve of 91% (95% confidence
      interval: 86% to 95%) for prediction of abnormal myocardial mechanical relaxation
      with a sensitivity and specificity of 80% and 84%, respectively. The spECG
      demonstrated more accurate diagnostic performance in individuals age >=60 years
      as well as those with obesity or hypertension, compared with their respective
      counterparts. Prediction of low early diastolic relaxation velocity (e') also
      correctly identified concomitant significant underlying coronary artery disease
      in 23 of 28 cases (82%). Furthermore, a superior integrated discrimination and
      net reclassification improvement was observed for spECG over clinical features
      and traditional ECG. CONCLUSIONS: The spECG provides a robust prediction of
      abnormal myocardial relaxation. These data suggest a potential role for spECG as
      a novel screening strategy for identifying patients at risk for LVDD who would
      benefit undergoing echocardiographic evaluations.

PMID- 29650122
TI  - Machine Learning for Electrocardiographic Diagnosis of Left Ventricular Early
      Diastolic Dysfunction.

PMID- 29650124
TI  - Phenotypic Landscape and Risk Management in Long QT Syndrome: Nudging Forward.

PMID- 29650123
TI  - Interplay Between Genetic Substrate, QTc Duration, and Arrhythmia Risk in
      Patients With Long QT Syndrome.
AB  - BACKGROUND: Long QT syndrome (LQTS) is a common inheritable arrhythmogenic
      disorder, often secondary to mutations in the KCNQ1, KCNH2, and SCN5A genes. The
      disease is characterized by a prolonged ventricular repolarization (QTc interval)
      that confers susceptibility to life-threatening arrhythmic events (LAEs).
      OBJECTIVES: This study sought to create an evidence-based risk stratification
      scheme to personalize the quantification of the arrhythmic risk in patients with
      LQTS. METHODS: Data from 1,710 patients with LQTS followed up for a median of 7.1
      years (interquartile range [IQR]: 2.7 to 13.4 years) were analyzed to estimate
      the 5-year risk of LAEs based on QTc duration and genotype and to assess the
      antiarrhythmic efficacy of beta-blockers. RESULTS: The relationship between QTc
      duration and risk of events was investigated by comparison of linear and cubic
      spline models, and the linear model provided the best fit. The 5-year risk of
      LAEs while patients were off therapy was then calculated in a multivariable Cox
      model with QTc and genotype considered as independent factors. The estimated risk
      of LAEs increased by 15% for every 10-ms increment of QTc duration for all
      genotypes. Intergenotype comparison showed that the risk for patients with LQT2
      and LQT3 increased by 130% and 157% at any QTc duration versus patients with
      LQT1. Analysis of response to beta-blockers showed that only nadolol reduced the
      arrhythmic risk in all genotypes significantly compared with no therapy (hazard
      ratio: 0.38; 95% confidence interval: 0.15 to 0.93; p = 0.03). CONCLUSIONS: The
      study provides an estimator of risk of LAEs in LQTS that allows a granular
      estimate of 5-year arrhythmic risk and demonstrate the superiority of nadolol in
      reducing the risk of LAEs in LQTS.

PMID- 29650125
TI  - Restenosis, Stent Thrombosis, and Bleeding Complications: Navigating Between
      Scylla and Charybdis.
AB  - The field of interventional cardiology has significantly evolved over 40 years by
      overcoming several challenges. The introduction of first-generation drug-eluting
      stents significantly reduced the rates of restenosis, but at the expense of an
      increase of late stent thrombosis. Prolonged antithrombotic therapy reduced rates
      of stent thrombosis, but at the cost of increased bleeding. Although the advent
      of second-generation drug-eluting stents subsequently reduced the incidence of
      late stent thrombosis, its permanent nature prevents full recovery of vascular
      structure and function with accordant risk of very late stent failure. In the
      present era of interventional cardiology, the tradeoff between stent thrombosis,
      restenosis, and bleeding presents as a particularly complex challenge. In this
      review, the authors highlight major contributors of late/very late stent
      thrombosis while targeting stent restenosis, and they discuss evolutionary
      advances in stent technology and antiplatelet therapy, to further improve upon
      the care of patients with coronary artery disease.

PMID- 29650126
TI  - Myocardial Interstitial Fibrosis in Heart Failure: Biological and Translational
      Perspectives.
AB  - Myocardial interstitial fibrosis contributes to left ventricular dysfunction
      leading to the development of heart failure. Basic research has provided abundant
      evidence for the cellular and molecular mechanisms behind this lesion and the
      pathways by which it imparts a detrimental impact on cardiac function.
      Translation of this knowledge, however, to improved diagnostics and therapeutics
      for patients with heart failure has not been as robust. This is partly related to
      the paucity of biomarkers to accurately identify myocardial interstitial fibrosis
      and to the lack of personalized antifibrotic strategies to treat it in an
      effective manner. This paper summarizes current knowledge of the mechanisms and
      detrimental consequences of myocardial interstitial fibrosis, discusses the
      potential of circulating and imaging biomarkers available to recognize different
      phenotypes of this lesion and track their clinical evolution, and reviews the
      currently available and potential future therapies that allow its individualized
      management in heart failure patients.

PMID- 29650127
TI  - Fondaparinux and Direct Oral Anticoagulants: Promising Anticoagulant for
      Management of Heparin-Induced Thrombocytopenia.

PMID- 29650128
TI  - Reply: Fondaparinux and Direct Oral Anticoagulants: Promising Anticoagulant for
      Management of Heparin-Induced Thrombocytopenia.

PMID- 29650129
TI  - Correction.

PMID- 29650130
TI  - Effects of Single-Session Group Mantra-meditation on Salivary Immunoglobulin A
      and Affective State: A Psychoneuroimmunology Viewpoint.
AB  - OBJECTIVES: Based on existing psychoneuroimmunological insights, the present
      study aimed at investigating possible effects of a single-session group mantra
      meditation on salivary immunoglobulin A (s-IgA) and affective states. MATERIALS
      AND METHODS: A controlled pretest-posttest study enrolled 30 healthy women (mean
      age 44 +/- 3 years) through a multi-stage random sampling method from yoga clubs
      in Shiraz (Feb-Dec, 2016). Subjects were randomly assigned to experimental (n =
      15) and control (n = 15) groups. Participants in both the groups attended a
      structured introductory lecture about mantra-meditation after which those in the
      experimental group meditated for 20min. Saliva samples were collected after the
      intervention, and the participants' affective states were examined by a qualified
      clinical psychologist blinded to the intervention using the positive and negative
      affect schedule questionnaire at sequential time-points, i.e., baseline, post
      meditation, and one hour later. Similar assessments were done for the control
      group subjects. The enzyme-linked immunosorbent assay was used to test saliva
      samples for the IgA titer. The s-IgA and the positive and negative affect
      schedule (PANAS) test results were statistically evaluated using an analysis of
      variance. RESULT: The mean s-IgA titer in the experimental group at 'post
      meditation' and '1-hour later' time-points were found to be statistically
      different from those of the control group (P < .05). In addition, results
      indicated a significant change in affect among experimental group subjects as
      compared to controls (P < .05). CONCLUSION: Our findings suggest that "group
      mantra-meditation" training even for a single session may positively influence
      some immunological components and improve affective states. As a simple and low
      cost psychoneurobehavioral intervention, this method may offer mental-health
      benefits at nursing homes as well as group-therapies.

PMID- 29650131
TI  - Current Staging Strategies for Muscle-Invasive Bladder Cancer and Upper Tract
      Urothelial Cell Carcinoma.
AB  - Please note, the synopsis was used from your supplied original manuscript, and
      not the accompanying abstract, per journal style: This article discusses current
      staging strategies in muscle-invasive bladder cancer and upper tract urothelial
      cell carcinoma. Current staging methods can help identify patients with localized
      or metastatic disease but are subject to limitations which must be considered.

PMID- 29650132
TI  - Optimal Timing of Chemotherapy and Surgery in Patients with Muscle-Invasive
      Bladder Cancer and Upper Urinary Tract Urothelial Carcinoma.
AB  - Radical cystectomy with bilateral pelvic lymph node dissection is the standard of
      care for patients with clinically localized muscle-invasive bladder cancer.
      Survival after radical cystectomy is associated with final pathologic staging.
      Survival decreases with increasing pT stage because of the presence of occult
      micrometastases, indicating the need for systemic chemotherapy. Systemic
      chemotherapy is delivered as either neoadjuvant therapy preoperatively, or as
      adjuvant therapy postoperatively. This article reviews the evidence for
      neoadjuvant and adjuvant chemotherapy for the treatment of muscle-invasive
      bladder and upper tract urothelial cancer and offers recommendations based on
      these data and recently updated clinical guidelines.

PMID- 29650133
TI  - Contemporary Preoperative and Intraoperative Management of the Radical Cystectomy
      Patient.
AB  - Radical cystectomy is a morbid procedure performed on an aging and often frail
      population. Nonetheless, advances in preoperative and intraoperative management
      have significantly improved patient outcomes. Preoperative optimization includes
      a focus on patient education, risk factor reduction, risk stratification,
      nutritional optimization, and bowel motility enhancement. Intraoperative
      optimization focuses on maintaining normothermia, restrictive fluid
      administration, minimization of blood transfusions, and nonopioid pain
      management.

PMID- 29650134
TI  - Robotic Cystectomy.
AB  - Retrospective observational studies support the utility of robotic-assisted
      radical cystectomy (RARC). Randomized controlled trials (RCTs) have shown that
      RARC with extracorporeal urinary diversion may lead to decreased estimated blood
      loss, decreased rate of transfusion, similar oncologic outcomes, cost
      effectiveness, and variable increased operative times. Although RCTs comparing
      RARC with open radical cystectomy are currently ongoing, it may be several years
      before the utility of RARC is known. The discussion on the role of cystectomy,
      indications, outcomes, care pathways, access to high-volume care centers, and
      efforts to decrease complications may prove as important as the technique itself.

PMID- 29650135
TI  - Robotic Nephroureterectomy.
AB  - Upper tract urothelial carcinoma is a rare malignancy that has an abundance of
      surgical treatment options, including open, laparoscopic, robotic, and endoscopic
      approaches. As advances in technology allow for shorter, less morbid operations,
      the variation in care of this uncommon disease has raised concerns about
      compromising oncologic principles. Many institutions have described their
      experience with promising results; however, there is a paucity of high-quality
      data that supports the use of robotic surgery as a new gold standard. This
      article describes how to perform the operation using a single-dock method and
      reviews contemporary literature on perioperative and oncologic outcomes.

PMID- 29650136
TI  - Role and Indications of Organ-Sparing "Radical" Cystectomy: The Importance of
      Careful Patient Selection and Counseling.
AB  - Organ-sparing cystectomy remains an operation for a highly selected patient
      population that can offer similar oncologic outcomes but improved sexual function
      in men and women. Occult prostate cancer in men may occur even with screening but
      the majority is of clinical insignificance. Paramount to patient selection are
      oncologic concerns, but preoperative sexual function, age, performance status,
      and postoperative expectations must also be evaluated during patient selection.
      Improved diagnostic and surveillance tools may facilitate and improve patient
      selection in the future.

PMID- 29650137
TI  - Lymphadenectomy for Muscle-Invasive Bladder Cancer and Upper Tract Urothelial
      Cell Carcinoma.
AB  - There are currently no reported randomized trials that characterize the staging
      or therapeutic benefit of performing a lymph node dissection in either bladder
      cancer or upper tract urothelial carcinoma. Several unanswered questions remain
      in this domain focused on the indications and patient selection for pelvic lymph
      node dissection, extent of dissection, its impact on outcome, and potential
      risks. However, the results of observational studies suggest that the burden of
      metastasis is high in both diseases when muscle invasive and performing a
      lymphadenectomy can provide prognostic information and yield therapeutic benefit.

PMID- 29650138
TI  - Enhanced Recovery After Surgery Pathways: Role and Outcomes in the Management of
      Muscle Invasive Bladder Cancer.
AB  - Radical cystectomy remains the gold standard therapy for the treatment of muscle
      invasive urothelial carcinoma, yet is accompanied by significant rates of
      perioperative complications and readmission. Enhanced recovery protocols aim to
      apply evidence-based principles of care to ameliorate the morbidity of this
      procedure by enabling better tolerance of and recovery from radical cystectomy.
      Multiple patient series have demonstrated the capacity for enhanced-recovery
      after-surgery (ERAS) principles to improve outcomes among patients undergoing
      radical cystectomy through decreased incidence of gastrointestinal complications
      and decreased length of hospitalization without increased readmissions or overall
      morbidity. Opportunities remain for adoption of established ERAS principles.

PMID- 29650139
TI  - Follow-up Management of Cystectomy Patients.
AB  - Bladder cancer is the sixth leading cancer in the United States. Radical
      cystectomy is a lifesaving procedure for bladder cancer with or without muscle
      invasion. Radical cystectomy is performed on 39% of these patients, and 35% will
      have a life-threatening recurrence. Distant metastases are the most common;
      local, upper tract, and urethral recurrence can also occur. Surveillance after
      cystectomy is critical to diagnosing recurrence early. Functional complications
      after urinary diversion include bowel dysfunction, vitamin B12 deficiency,
      acidosis, electrolyte abnormalities, osteopenia, nephrolithiasis, urinary tract
      infections, renal functional decline, and urinary obstruction, which can be
      reversed when diagnosed early.

PMID- 29650140
TI  - Quality of Life After Radical Cystectomy.
AB  - Approximately 1 in 5 new cases of clinically localized bladder cancer is muscle
      invasive and requires the patient to choose from 1 of 2 prevailing options for
      treatment: radical cystectomy or radiation to the bladder. However, these
      treatments are associated with detrimental effects on patient well-being and
      quality of life, particularly with respect to functional independence, urinary
      and sexual function, social and emotional health, body image, and psychosocial
      stress. Compared with the literature on other malignancies like breast or
      prostate cancer, high-quality studies evaluating the effects of bladder cancer
      treatment on quality of life are lacking.

PMID- 29650141
TI  - Adjuvant Therapy in Muscle-Invasive Bladder Cancer and Upper Tract Urothelial
      Carcinoma.
AB  - This article summarizes the role of adjuvant chemotherapy in muscle-invasive and
      transitional cell carcinoma of the bladder and upper urinary tract.

PMID- 29650142
TI  - Endoscopic Approaches to Upper Tract Urothelial Carcinoma.
AB  - A select group of patients with upper tract urothelial carcinoma (UTUC) may meet
      indications for endoscopic management. Strategies for disease management are
      provided, based on a comprehensive review of the data using PubMed and Medline
      databases and marrying this with our experience with endoscopic management of
      UTUC. Endoscopic management of UTUC via retrograde or antegrade approaches is a
      viable treatment option for appropriately selected patients with low-risk UTUC,
      including those with low-grade, low-volume, and solitary tumors. However,
      recurrence risk limits these procedures to compliant patients under a vigilant
      surveillance program. Efficacious adjuvant therapies are needed to reduce local
      recurrences.

PMID- 29650143
TI  - Perioperative Immunotherapy in Muscle-Invasive Bladder Cancer and Upper Tract
      Urothelial Carcinoma.
AB  - Neoadjuvant chemotherapy improves survival in patients with muscle-invasive
      bladder cancer. However, a significant proportion of patients are ineligible for
      cisplatin owing to renal impairment or other medical comorbidities. The
      introduction of anti-programmed cell death protein 1/programmed death-ligand
      1(PD1/PD-L1) checkpoint inhibitors has redefined the therapeutic landscape for
      platinum-resistant urothelial cancers; their clinical efficacy and favorable
      toxicity render these agents attractive therapeutic options either as monotherapy
      or in combination with other agents in earlier disease states, including muscle
      invasive disease. We review potential perioperative immunotherapy strategies,
      ongoing clinical trials and areas of unmet needs, including upper tract disease
      and non-urothelial cancers.

PMID- 29650144
TI  - Erratum.

PMID- 29650145
TI  - Current Management of Invasive Bladder and Upper Tract Urothelial Cancer.

PMID- 29650146
TI  - Smelling the metal: Volatile organic compound emission under Zn excess in the
      mint Tetradenia riparia.
AB  - This work investigated the effect of Zn excess on growth, metal accumulation and
      photosynthetic changes in Tetradenia riparia, in relation to possible variations
      in the composition of the plant volatilome. Experiments were carried out in
      hydroponics exposing plants to a range of Zn concentrations. Zinc excess
      negatively affected plant growth in a dose-dependent manner. The metal was
      accumulated proportionally to its concentration in the medium and preferentially
      allocated to roots. All the photosynthetic parameters and the concentration of
      some photosynthetic pigments were negatively affected by Zn, whereas the level of
      leaf total soluble sugars remained unchanged. Twenty-three different VOCs were
      identified in the plant volatilome. Each compound was emitted at a different
      level and intensity of emission was manifold increased by the presence of Zn in
      the growth medium. The Zn-induced compounds could represent both an adaptive
      response (f.i. methanol, acetylene, C6-aldehydes, isoprene, terpenes) and a
      damage by-product (f.i. propanal, acetaldehyde, alkyl fragments) of the metal
      presence in the culture medium. Given that the Zn-mediated induction of those
      VOCs, considered protective, occurred even under a Zn-limited photosynthetic
      capacity, our work supports the hypothesis of an active role of such molecules in
      an adaptive plant response to trace metal stress.

PMID- 29650147
TI  - Source-sink relations of sunflower plants as affected by a parasite modifies
      carbon allocations and leaf traits.
AB  - Sunflower broomrape (Orobanche cumana) is a root holoparasitic plant causing
      major damage to sunflower (Helianthus annuus L.). Parasite infection initiates
      source-sink relations between the parasite (sink) and the host (source),
      allocating carbohydrates, water and nutrients to the parasite. The primary aim of
      the current study was to explore responses of sunflower to broomrape parasitism,
      specifically to examine alternations in leaf area, leaf mass per area (LMA),
      mesophyll structure and root hydraulic conductivity. Leaf changes revealed
      modifications similar to described previously in shade adapted plants, causing
      larger and thinner leaves. These traits were accompanied with significantly
      higher root hydraulics. These changes were caused by carbohydrate depletion due
      to source-sink relationships between the host and parasite. An Imazapic herbicide
      (ALS inhibitor) was used for controlling broomrape attachments and by to
      investigate the plasticity of the traits found. Broomrape infected plants which
      were treated with Imazapic had leaves similar to non-infected plants, including
      mesophyll structure and carbon assimilation rates. These results demonstrated
      source-sink effects of broomrape which cause a low-light-like acclimation
      behavior which is reversible.

PMID- 29650148
TI  - Functions and regulation of phosphate starvation-induced secreted acid
      phosphatases in higher plants.
AB  - Phosphorus is essential for plant growth and development, but levels of inorganic
      phosphate (Pi), the major form of phosphorus that plants assimilate, are quite
      limiting in most soils. To cope with Pi deficiency, plants trigger a suite of
      adaptive responses, including the induction and secretion of acid phosphatases
      (APases). In this article, we describe how Pi starvation-induced (PSI) APases are
      analyzed, and we provide a brief historical review of their identification. We
      then discuss the current understanding of the functions of PSI-secreted APases
      and how these APases are regulated at the molecular level. Finally, we provide a
      perspective on the future direction of research in this field.

PMID- 29650149
TI  - A Golden Gate and Gateway double-compatible vector system for high throughput
      functional analysis of genes.
AB  - A major research topic nowadays is to study and understand the functions of the
      increasing number of predicted genes that have been discovered through the
      complete genome sequencing of many plant species. With the aim of developing
      tools for rapid and convenient gene function analysis, we have developed a set of
      "pGate" vectors based on the principle of Golden gate and Gateway cloning
      approaches. These vectors combine the positive aspects of both Golden gate and
      Gateway cloning strategies. pGate vectors can not only be used as Golden gate
      recipient vectors to assemble multiple DNA fragments in a pre-defined order, but
      they can also work as an entry vector to transfer the assembled DNA fragment(s)
      to a large number of already-existing, functionally diverse, Gateway compatible
      destination vectors without adding additional nucleotides during cloning. We show
      the pGate vectors are effective and convenient in several major aspects of gene
      function analyses, including BiFC (Bimolecular fluorescence complementation) to
      analyze protein-protein interaction, amiRNA (artificial microRNA) candidate
      screening and as assembly of CRISPR/Cas9 (Clustered regularly interspaced short
      palindromic repeats, CRISPR-associated protein-9 nuclease) system elements
      together for genome editing. The pGate system is a practical and flexible tool
      which can facilitate plant gene function research.

PMID- 29650150
TI  - The SWI/SNF subunit SWI3B regulates IAMT1 expression via chromatin remodeling in
      Arabidopsis leaf development.
AB  - The SWI/SNF complex is crucial to chromatin remodeling in various biological
      processes in different species, but the distinct functions of its components in
      plant development remain unclear. Here we uncovered the role of SWI3B, a subunit
      of the Arabidopsis thaliana SWI/SNF complex, via RNA interference. Knockdown of
      SWI3B resulted in an upward-curling leaf phenotype. Further investigation showed
      that the RNA level of IAA carboxyl methyltransferase 1 (IAMT1), encoding an
      enzyme involved in auxin metabolism, was dramatically elevated in the knockdown
      (SWI3B-RNAi) plants. In addition, activation of IAMT1 produced a leaf-curling
      phenotype similar to that of the SWI3B-RNAi lines. Database analysis suggested
      that the last intron of IAMT contains a site of polymerase V (Pol V) stabilized
      nucleosome, which may be associated with SWI3B. Data from a micrococcal nuclease
      (MNase) digestion assay showed that nucleosome occupancy around this site was
      downregulated in the leaves of SWI3B-RNAi plants. In addition, knockdown of IAMT1
      in the SWI3B-RNAi background repressed the abnormal leaf development. Thus, SWI3B
      mediated chromatin remodeling is critical in regulating the expression of IAMT1
      in leaf development.

PMID- 29650151
TI  - Characterization of l-aspartate oxidase from Arabidopsis thaliana.
AB  - The flavoprotein l-aspartate oxidase (LASPO) is the first enzyme of the de novo
      biosynthetic pathway of NAD+ in plants. Although LASPO is considered pivotal to
      maintain NAD+ homeostasis, it has not been hitherto characterized in plants.
      Here, the cDNA encoding the LASPO from the model plant Arabidopsis thaliana
      (AtLASPO, At5g14760) has been cloned and expressed in Escherichia coli for
      subsequent enzyme characterization. The purified AtLASPO enzyme displayed a Km of
      0.79 mM for l-aspartate and a kcat of 0.25 s-1. We could further detect an l
      aspartate: fumarate oxidoreductase activity of the recombinant plant enzyme. In
      addition, results indicated that NADP+ but not NAD+, and even more strongly NADH,
      inhibited AtLASPO at physiological concentrations by competing with the flavin
      for binding to the apoprotein. LASPO optimal pH and temperature, as well as
      plastidial pyridine nucleotide concentrations may contribute to an increased NAD+
      production in planta. Moreover, in Arabidopsis thaliana AtLASPO gene expression
      exhibited a clear correlation between LASPO activity and NAD+ levels, thus
      demonstrating that plant LASPO catalyzes a key metabolic step of NAD+ synthesis.

PMID- 29650152
TI  - The antagonistic basic helix-loop-helix partners BEE and IBH1 contribute to
      control plant tolerance to abiotic stress.
AB  - The bHLH family is composed by canonical and non-canonical transcription factors
      (TFs) that differ in the presence or absence of their DNA-binding domain,
      respectively. Since both types of bHLH proteins are able to dimerize, their
      relative abundance impacts their biological activity. Among this TF family BEE
      and IBH are canonical and non-canonical bHLHs, respectively and previous reports
      indicated that BEE2 and IBH1 dimerize. Wondering whether BEE TFs participate in
      the abiotic stress response and how the dimerization with IBH1 could regulate
      their role in Arabidopsis, double bee1/bee2 and triple bee1/bee2/bee3 mutants
      were tested under salinity and drought stresses. The bee1/bee2/bee3 mutant showed
      an enhanced tolerance whereas the double mutant behaved similar to wild type
      plants. These results indicated that BEE genes play a role in the stress response
      and also put in evidence the redundancy within the BEE family. Moreover, ectopic
      expression of IBH1 on different mutant backgrounds improved plant tolerance to
      abiotic stress, independently of the background. However, the yield of these
      transgenic plants was penalized with abortive seeds. Our results suggest that BEE
      genes are negative regulators of physiological responses to abiotic stress
      whereas IBH1 is a positive modulator via different pathways, one of them
      involving BEE TFs.

PMID- 29650153
TI  - Increasing genetic variability in oilseed rape (Brassica napus) - Genotypes and
      phenotypes of oilseed rape transformed by wild type Agrobacterium rhizogenes.
AB  - Brassica napus (oilseed rape) is a major oil crop worldwide. Due to the short
      domestication period of oilseed rape the genetic variability is limited compared
      to other crops. Transfer of rol and aux genes from Agrobacterium rhizogenes is
      used in horticulture to increase genetic variability. In the current study, we
      explore transformation by A. rhizogenes as a biotechnological approach in
      breeding for more branched and shorter oilseed rape. In the 2nd generation of
      transformed oilseed rape, branch numbers increased significantly by 49% from 7.7
      +/- 0.4 to 11.5 +/- 1.9 when comparing rol+/aux+ plants with WT. Simultaneously,
      the apical height of plants was reduced by 25% from 81.3 +/- 1.9 cm to 62.4 +/-
      6.7 cm in rol+/aux+ plants at the onset of flowering. Reproductive parameters
      affecting yield as seed size and number were negatively affected in rol+/aux+
      plants. Interestingly, oil composition was changed in rol+/aux+ seeds. Oleic acid
      (omega9) contents were reduced by more than 3% whereas alpha-linolenic acid
      (omega6) increased by more than 25% in mature seeds. To obtain shorter and more
      branched breeding material of oilseed rape we suggest crossing plants with the
      rol+/aux+ genotype back into the parental breeding line. This could reduce the
      negative impact of rol+/aux+ on yield.

PMID- 29650154
TI  - Genomic-based multiple-trait evaluation in Eucalyptus grandis using dominant DArT
      markers.
AB  - We investigated the impact of combining the pedigree- and genomic-based
      relationship matrices in a multiple-trait individual-tree mixed model (a.k.a.,
      multiple-trait combined approach) on the estimates of heritability and on the
      genomic correlations between growth and stem straightness in an open-pollinated
      Eucalyptus grandis population. Additionally, the added advantage of incorporating
      genomic information on the theoretical accuracies of parents and offspring
      breeding values was evaluated. Our results suggested that the use of the combined
      approach for estimating heritabilities and additive genetic correlations in
      multiple-trait evaluations is advantageous and including genomic information
      increases the expected accuracy of breeding values. Furthermore, the multiple
      trait combined approach was proven to be superior to the single-trait combined
      approach in predicting breeding values, in particular for low-heritability
      traits. Finally, our results advocate the use of the combined approach in forest
      tree progeny testing trials, specifically when a multiple-trait individual-tree
      mixed model is considered.

PMID- 29650155
TI  - Strigolactones and interaction with auxin regulating root elongation in tall
      fescue under different temperature regimes.
AB  - Strigolactones (SL) have recently been found to play roles in regulating root
      development. However, it remains unclear how SL may mediate root elongation of
      perennial grass species under different temperatures that differentially affect
      root growth. The objectives of this study were to examine effects of SL on root
      elongation of tall fescue and to examine the interactive effects of SL and auxin
      in regulating root growth under both non-stress and heat stress conditions. Tall
      fescue (cv. 'Kentuck-31') plants were treated with GR24 (a synthetic
      strigolactones), NAA (alpha-naphthylacetic acid), or NPA (auxin transport
      inhibitor N-1-naphthylphalamic acid) or their combination under non-stress
      control and heat stress (35/30  degrees C) in growth chamber. Crown root
      elongation was evaluated by measuring root length. Cell number and length in root
      tips were measured under confocal microscope. Expression levels of genes related
      to cell growth, SL signaling and auxin transport were determined. SL promoted
      crown root elongation in tall fescue under normal temperature and heat stress,
      and alleviated heat-inhibition of root growth. GR24-enhanced root elongation was
      accompanied with the increase in cell numbers, up-regulation of cell cycle
      related genes, and down-regulation auxin transport-related genes in crown root
      tips of tall fescue. The positive effects of SL for promoting crown root
      elongation in tall fescue under both non-stress and heat stress could be mainly
      due to its regulation of cell division and involve the interference of auxin
      transport.

PMID- 29650156
TI  - Temperature variation caused by sowing dates significantly affects floral
      initiation and floral bud differentiation processes in rapeseed (Brassica napus
      L.).
AB  - To understand the influence of temperature on floral initiation and to reveal the
      relationship between floral bud development and yield potential of rapeseed
      (Brassica napus L.), early- ("1358"), intermediate- ("Zhongshuang No.11") and
      late- ("Zheshuang No.8") maturity genotypes were sown on different sowing dates
      under field conditions during four crop seasons. A multiplicative model was
      introduced to distinguish and quantify the effects of photoperiod and temperature
      on pre-floral initiation phase. Parameters in this model showed that early
      maturity genotype was more sensitive to photoperiod; while late-maturity genotype
      was more sensitive to vernalization. The relationships between cumulative
      temperature and mean temperature of pre-floral initiation phase could be well
      descried by exponential equation. The developmental rate of pre-floral initiation
      phase against mean daily temperature displayed an asymmetrical distribution, and
      it decreased rapidly when the mean temperature exceeded the optimum. Leaf
      primordia differentiated from the shoot apical meristem showed significant linear
      relationship with the thermal time at pre-floral initiation phase; dynamic change
      of floral bud differentiated from the shoot apical meristem robustly fitted to a
      sigmoidal logistic curve. According to the fitted logistic equation, the maximum
      differentiation rate varied from 1.7 to 4.1 per 10  degrees Cd due to different
      sowing dates and genotypes. Averaged across growing seasons, sowing dates and
      genotypes, bud degeneration rate was 33% on the main raceme, and varied from 58%
      to 99% on the seven primary branches. The yield showed a significant correlation
      with floral bud number although the latter showed serious degeneration. In
      conclusion, the floral bud quantity largely determines rapeseed yield, and thus
      the genotypes with strong vernalization requirement should be planted early to
      extend the vegetative stage to achieve more fertile floral buds while the
      genotypes with weak vernalization requirement should be planted late to avoid
      flowering in chilling environment.

PMID- 29650157
TI  - RNA interference of GhPEPC2 enhanced seed oil accumulation and salt tolerance in
      Upland cotton.
AB  - Phosphoenolpyruvate carboxylase (PEPCase) mainly produces oxaloacetic acid for
      tricarboxylic acid (TCA) cycle. Here we reported that GhPEPC2 silencing with
      PEPC2-RNAi vector could regulate oil and protein accumulation in cottonseeds. In
      GhPEPC2 transgenic plants, PEPCase activities in immature embryos were
      significantly reduced, and the oil content in seed kernel was increased 7.3
      percentages, whereas total proteins decreased 5.65 percentages. Compared to wild
      type, agronomical traits of transgenic plant were obviously unaffected.
      Furthermore, gene expression profile of GhPEPC2 transgenic seeds were
      investigated using RNA-seq, most lipid synthesis related genes were up-regulated,
      but amino acid metabolic related genes were down-regulated. In addition, the
      GhPEPC2 transgenic cotton seedlings were stressed using sodium salts at seedling
      stage, and the salt tolerance was significantly enhanced. Our observations of
      GhPEPC2 in cotton would shade light on understanding the regulation of oil
      content, protein accumulation and salt tolerance enhancement in other plants.

PMID- 29650158
TI  - Saving for a rainy day: Control of energy needs in resurrection plants.
AB  - Plants constantly respond to threats in their environment by balancing their
      energy needs with growth, defence and survival. Some plants such as the small
      group of resilient angiosperms, the resurrection plants, do this better than
      most. Resurrection plants possess the capacity to tolerate desiccation in
      vegetative tissue and upon watering, regain full metabolic capacity within 72 h.
      Knowledge of how these plants survive such extremes has advanced in the last few
      decades, but the molecular mechanics remain elusive. Energy and water metabolism,
      cell cycle control, growth, senescence and cell death all play key roles in
      resurrection plant stress tolerance. Some resurrection plants suppress growth to
      improve energy efficiency and survival while sensitive species exhaust energy
      resources rapidly, have a diminished capacity to respond and die. How do the
      stress and energy metabolism responses employed by resurrection plants differ to
      those used by sensitive plants? In this perspective, we summarise recent findings
      defining the relationships between energy metabolism, stress tolerance and
      programmed cell death and speculate important roles for this regulation in
      resurrection plants. If we want to harness the strategies of resurrection plants
      for crop improvement, first we must understand the processes that underpin energy
      metabolism during growth and stress.

PMID- 29650159
TI  - Expression of CLAVATA3 fusions indicates rapid intracellular processing and a
      role of ERAD.
AB  - The 12 amino acid peptide derived from the Arabidopsis soluble secretory protein
      CLAVATA3 (CLV3) acts at the cell surface in a signalling system that regulates
      the size of apical meristems. The subcellular pathway involved in releasing the
      peptide from its precursor is unknown. We show that a CLV3-GFP fusion expressed
      in transfected tobacco protoplasts or transgenic tobacco plants has very short
      intracellular half-life that cannot be extended by the secretory traffic
      inhibitors brefeldin A and wortmannin. The fusion is biologically active, since
      the incubation medium of protoplasts from CLV3-GFP-expressing tobacco contains
      the CLV3 peptide and inhibits root growth. The rapid disappearance of intact CLV3
      GFP requires the signal peptide and is inhibited by the proteasome inhibitor
      MG132 or coexpression with a mutated CDC48 that inhibits endoplasmic reticulum
      associated protein degradation (ERAD). The synthesis of CLV3-GFP is specifically
      supported by the endoplasmic reticulum chaperone endoplasmin in an in vivo assay.
      Our results indicate that processing of CLV3 starts intracellularly in an early
      compartment of the secretory pathway and that ERAD could play a regulatory or
      direct role in the active peptide synthesis.

PMID- 29650160
TI  - Manipulation of plant architecture and flowering time by down-regulation of the
      GRAS transcription factor SlGRAS26 in Solanum lycopersicum.
AB  - Previous studies suggest that GRAS transcription factors act as essential
      regulators, not only in plant growth and development but also in response to
      biotic and abiotic stresses. Recently, 53 GRAS proteins have been identified, but
      only a few of them have been functionally studied in tomato. Here, we isolated a
      novel GRAS transcription factor SlGRAS26, its down-regulation generated
      pleiotropic phenotypes, including reduced plant height with more lateral shoots,
      internode length, leaf size, even leaflets, accelerated flowering transition and
      decreased trichome number. Transcription analysis showed that down-regulation of
      SlGRAS26 altered vegetative growth by suppressing gibberellin (GA) biosynthesis
      genes and activating the GA inactivating genes, thereby reducing endogenous GA
      content in transgenic plants. SlGRAS26 may regulate the initiation of lateral
      buds by regulating the expression of Blind (BL) and BRC1b. The earlier initiation
      of flower buds in transgenic lines may be controlled by significant up-regulation
      of SFT, CO1, SBP3, SBP13, and SBP15 genes, related to flowering time. These
      results demonstrate that SlGRAS26 may play a vital role in the initiation of
      lateral and inflorescence meristems in tomato.

PMID- 29650161
TI  - Molecular and functional characterization of ShNAC1, an NAC transcription factor
      from Solanum habrochaites.
AB  - NAC transcription factors (TFs) are important regulators of plant adaptation to
      abiotic stress. In this study, we functionally characterized an NAC TF, ShNAC1,
      from Solanum habrochaites. ShNAC1 was up-regulated by drought, cold, and salt
      stresses, and it displayed lower expression at the late stage of stress
      treatments than its orthologous gene in S. lycopersicum. Overexpression of ShNAC1
      in tomato resulted in reduced cold, drought, and salt tolerance. Additionally,
      ShNAC1 displayed the highest expression in senescent leaf, and overexpressing
      ShNAC1 accelerated salt- and dark-induced leaf senescence. ShNAC1 was located in
      the nucleus without transactivation activity. RNA-seq analysis revealed that 81%
      (190 out of 234) differentially-expressed genes (DEGs) showed down-regulation in
      the transgenic line L2 compared with wild-type, suggesting that ShNAC1 may
      function as a transcriptional repressor. Among these down-regulated DEGs, many
      were involved in stress responses, such as SlHKT1;1, SlMAPKKK59, SlJA2, SlTIL,
      SlALDH2B1, etc. Noticeably, one ACS gene and three ACO genes involved in ethylene
      biosynthesis were up-regulated, while seven ERF genes in the ethylene signal
      transduction pathway were down-regulated in the transgenic lines, respectively.
      Our results suggested that ShNAC1 negatively regulates tolerance to abiotic
      stress in tomato probably by modulating the ethylene biosynthesis and signal
      transduction pathways.

PMID- 29650162
TI  - Relation between hypericin content and morphometric leaf parameters in Hypericum
      spp.: A case of cubic degree polynomial function.
AB  - Higher plants often accumulate secondary metabolites in multicellular structures
      or in secretory reservoirs. Biotechnological production of such compounds by cell
      cultures lacking proper morphological structures is difficult, therefore
      possibilities for an efficient increase of their formation by organ cultures are
      being searched. The genus Hypericum comprises many species that store photoactive
      and phototoxic naphthodianthrones in the dark nodules on their above-ground
      parts. To date, the relation between the content of hypericins and their proto
      forms accumulated in the nodules, and morphological characters of the plant parts
      containing these structures has not been sufficiently explained. The content of
      hypericins and leaf morphology characters were measured in 12 selected diploid
      seed-derived Hypericum species cultured in vitro. The leaf volume and the volume
      of the nodules per leaf were calculated. Based on these data, a cubic degree
      polynomial regression model with high reliability was constructed. The model
      enables an estimate of the biosynthetic capacity of the cultures, and may be
      useful in designing the experiments aimed at elicitation of these unique
      secondary metabolites in shoot cultures of Hypericum spp. An analogous model may
      be developed for interpretation of experimental results for other plant species
      which accumulate metabolites in specialized morphological structures.

PMID- 29650163
TI  - Developing a health education game for preschoolers: What should we consider?
AB  - OBJECTIVE: To provide a comprehensive picture of what preschoolers prefer in
      computer game so that such game may be developed as a medium in health education.
      This is an important step to attract the children's attention so that the
      learning objectives from the educational game can be achieved. METHOD: This study
      used descriptive qualitative approach and involved seven children aged from three
      to six years. Purposive sampling was used to choose participants in accordance
      with the inclusion criteria. Participants were also chosen on the basis of
      whether they had good communication skills based on evaluation by their teachers.
      Data were collected through interviews and observation of types and models
      preferred by preschoolers followed by the analysis process using the Colaizzi
      method. RESULTS: Research showed there were three characteristic features of
      games preferred by preschoolers: 1) main character was preferred to be a moving
      creature, contain elements of fantasy, and have an attractive appearance; 2) game
      model was favored when it involved activities and rewards, and 3) the use of
      bright colors, particularly primary and secondary colors. CONCLUSIONS: To develop
      an appealing game for preschoolers, features such as the main character,
      activities in the games, and bright colors should be considered.

PMID- 29650164
TI  - What does the literature suggest about what carers need from mental health
      services for their own wellbeing? A Systematic Review.
AB  - OBJECTIVE: The aim of this study was to examine prior studies relating to carers'
      needs from mental health services for their own wellbeing. METHOD: A systematic
      approach was adopted for the literature review. The databases searched included
      MEDLINE, PSycINFO, EMBASE, and CINAHL, involving the use of search terms such as
      carers, mental health, and needs. The search was conducted in April 2012 and
      updated in December 2015. In total, 40 published papers were included in the
      review and were subsequently assessed for quality. For the data synthesis, a
      thematic analysis approach was employed to integrate the quantitative and
      qualitative evidence relating to carers' needs. RESULTS: Twenty-five of the
      reviewed studies were qualitative, 12 were quantitative, and 3 were mixed. Four
      major carer needs emerged from the synthesis: (1) holistic wellbeing of service
      users, (2) holistic wellbeing of carers, (3) supportive attitudes of
      professionals, and (4) carer involvement. All four of these needs, in fact,
      revolved around the carers' ill relatives. CONCLUSIONS: The studies reviewed
      suggest that while carers of people suffering from mental illness have a range of
      needs, they generally fail to offer straightforward information about their own
      needs.

PMID- 29650165
TI  - Therapeutic group therapy improved self-efficacy of school age children.
AB  - OBJECTIVE: The survival of children against disaster can be seen from their
      confidence in their ability (self-efficacy). Self-efficacy can help children to
      determine their ability against disaster as preparedness. The proper intervention
      to increase self-efficacy as a protective factor is a therapeutic group therapy.
      The aim of this research is to measure the increase of self-efficacy of school
      age children against earthquake and Tsunami through therapeutic group therapy.
      METHOD: This research used quasi-experimental design with pre-post-tests with
      control group. The sample involved in this study is 69 children, where 35 of them
      are in the experimental group while the rest 34 children are in the control group
      consisting of school children at the IV and V graders of elementary school.
      RESULTS: The result of the research showed that the self-efficacy of school
      children is improved significantly after being treated with therapeutic group
      therapy (p value < 0,05), those who were not treated with therapeutic group
      therapy have no significant improvement (p value > 0,05). CONCLUSIONS: This
      research is recommended to be conducted on school age children to improve their
      self-efficacy against disaster through health education.

PMID- 29650166
TI  - Family experiences in communicating with family members experiencing social
      isolation after hospitalization.
AB  - OBJECTIVE: Social isolation is one of the negative symptoms of schizophrenia that
      is likely to persist after hospitalization. This study aimed to describe family
      experiences in communicating with post-hospitalized family members experiencing
      social isolation. METHOD: This study used a descriptive phenomenology qualitative
      approach. The research sample consisted of seven participants selected by a
      purposive sampling method. Data were obtained through in-depth interviews with
      family members of people with schizophrenia who experienced social isolation
      after hospitalization. Data were analyzed using Colaizzi's method. RESULTS: Five
      themes emerged in this study: a) emotional reactions towards communication
      changes after hospitalization; b) family coping strategies in communicating with
      post-hospitalized clients; c) stigma and emotional expression as factors
      aggravating limited social interaction; d) types of family communication used to
      fulfill the psychological needs of patients, and e) family involvement in
      communicating with socially-isolated clients after hospitalization. CONCLUSIONS:
      Family communication becomes part of the adaptation of the family to caring for a
      family member with a chronic illness. It is recommended that nurses provide
      mental health education and psychological education on communication skills to
      family caregivers.

PMID- 29650167
TI  - The experience of parents implementing authoritarian parenting for their school
      age children.
AB  - OBJECTIVE: To explore families' experiences who use an authoritarian parenting
      style in caring for school-age children. METHOD: This was a qualitative study
      employing a phenomenological approach. The sampling method was to interview
      parents of school-age children living in the Central Maluku district in
      Indonesia. RESULTS: The findings of this study generated the following themes:
      (1) parents strictly controlled their children to achieve the parental values and
      expectations, (2) children failed to meet the parental values and expectations,
      and (3) problems experienced by the children were the results of the parenting
      style. CONCLUSIONS: This study suggested nursing professionals provide adequate
      information for parents with respect to parenting styles that may facilitate the
      optimal growth and development of the children. Future studies pertinent to
      cultural factors associated with authoritarian parenting were also suggested to
      better understand the cultural context of this parenting style.

PMID- 29650168
TI  - Thought stopping and supportive therapy can reduce postpartum blues and anxiety
      parents of premature babies.
AB  - OBJECTIVE: The parents of premature baby tend to be at risk undergoing postpartum
      blues and anxiety. It is due to many problems faced by postpartum mother of
      premature baby. This research is aim to identifying influence of thought stopping
      and supportive therapy of postpartum blues and anxiety parents of premature
      babies. METHOD: This is quantitative with quasi-experiment with control group
      pretest-posttest design and consecutive sampling method. Sample in this research
      are 62 postpartum mothers of premature babies in perinatal NICU (neonatal
      intensive care unit). RESULTS: The results show that there is significant
      decrease of postpartum blues and anxiety (p value = 0.000) in the group that was
      treated by using nursing intervention, thought stopping and supportive therapy
      and greater significant decrease than the group that was only treated by nursing
      intervention. CONCLUSIONS: Thought stopping and supportive therapy are able to
      decrease postpartum blues and anxiety parents of premature babies.

PMID- 29650169
TI  - The need for first aid education for adolescents.
AB  - OBJECTIVE: The objective of this study is to identify the need for basic first
      aid knowledge and skills among adolescents. METHOD: A cross-sectional study using
      multistage sampling was conducted among 375 secondary school students in Kuantan,
      Pahang, Malaysia. The survey was adapted from a Hong Kong Red Cross survey. A
      back to back translation of this instrument was carried out by two bilingual
      medical experts with Cronbach's alpha 0.8. The data were analyzed using SPSS
      (Statistical Package for the Social Sciences) in terms of descriptive analysis,
      and an independent t-test and chi-square test were carried out. RESULTS: There
      were 149 respondents from the lower form (grade level) and 226 respondents from
      the upper form. The majority of respondents (81.6%) were Malay. An independent t
      test revealed a significant association between knowledge and attitude, as
      students who scored higher on first aid questions showed a more positive attitude
      towards first aid (1.475%). There were also significant associations between race
      and experience learning first aid. CONCLUSIONS: Adolescents receive minimal first
      aid education. Thus, there is an urgent need to educate adolescents more in first
      aid to promote a safer community and to prevent any further injuries.

PMID- 29650170
TI  - Improving nurses' performance through remuneration: a literature review.
AB  - BACKGROUND: A remuneration system greatly influences the quality of nursing care
      and services. OBJECTIVE: The goal of this study was to identify the effects of a
      remuneration system on nurses' performance. DESIGN: This research used a
      literature review design and involved the analysis of 25 articles published in
      the Cumulative Index to Nursing and Allied Health Literature (CINAHL), MEDLINE,
      EMBASE, PsycINFO, and Global Health databases. The literature was limited to
      articles published in English between August 2006 and August 2015. RESULTS: The
      results of this study indicate that the improvement of remuneration systems has
      positive consequences in terms of nurses' performance and subsequent quality of
      healthcare services. A well-managed remuneration system has the potential to
      increase nurses' motivation, productivity, satisfaction, and even improve
      retention. In contrast, poorly managed and low remuneration contributes to a
      shortage of nurses due to high turnover rates. CONCLUSIONS: Adequate remuneration
      has been shown to improve nurses' performance and, consequently, improve the
      quality of healthcare. This literature review provides scientific evidence for
      decision-makers to consider the implementation of remuneration systems that
      include credentialing, re-credentialing, and career ladders. Future studies are
      suggested to investigate the development of well-managed remuneration systems for
      nurses.

PMID- 29650171
TI  - The association between stereotyping and interprofessional collaborative
      practice.
AB  - OBJECTIVE: This study aimed to identify the association between stereotyping and
      professional intercollaborative practice. METHOD: This study used a cross
      sectional analytical study involving physicians, nurses, pharmacists, and
      dietitians in a hospital in Jakarta, Indonesia, who were selected using the
      stratified random sampling method. Data was collected using the Student
      Stereotypes Rating Questionnaire (SSRQ) and the Assessment of Interprofessional
      Team Collaboration Scale (AITCS). The stereotyping level was analyzed based on a
      nine-point SSRQ, while interprofessional collaborative practice was scored based
      on partnership/shared decision-making, cooperation, and coordination. RESULTS:
      Stereotyping was shown to significantly correlate with interprofessional
      collaborative practice as measured by the SSRQ and AITCS. CONCLUSIONS: Poor
      interprofessional collaborative practice in subscale partnership/decision-making
      was dominant. Also, low-rating stereotyping was shown to be dominant with poor
      interprofessional collaborative practice. RECOMMENDATION: The research recommends
      that health care providers improve partnership/ decision-making skills for better
      interprofessional collaboration. For further research, it's recommended to
      explore another barrier of interprofessional collaborative practice.

PMID- 29650172
TI  - Nurse managers' perspectives on nurses' performance in mentorship program.
AB  - OBJECTIVE: The aim of this study was to explore the nurse managers' perspectives
      on nurses' performance in a mentorship program. METHOD: A cross-sectional survey
      was conducted on 51 nurse managers in Hospital Tengku Ampuan Afzan (HTAA),
      Kuantan, Pahang, by using modified and self-developed questionnaire with the
      Cronbach's alpha value 0.994. The data were analyzed by using descriptive
      statistics such as central tendency, frequency and percentage. RESULTS: The
      gender of respondents was predominantly female (100%). The mean age is 45.41 (SD
      +/- 4.51). In terms of level of education, the majority of the respondents
      (76.5%) were having a diploma. The majority has been in practice as a staff nurse
      between 11 to 20 years, and most of them have been practicing as nurse managers
      for about five years and less. Meanwhile, results showed that the nurse managers
      had positive perceptions upon newly graduated nurses' performance in the
      mentorship program, concerning on their effective communication, professional
      development and creative thinking. CONCLUSIONS: It is vital to identify the
      effectiveness of the mentorship program among nurses; hence, it enhances job
      satisfaction among new nurses.

PMID- 29650173
TI  - The relationship between nurses' job satisfaction and continuing professional
      development.
AB  - OBJECTIVE: To identify the correlation between nurse's perception of the
      continuing professional development (CPD) and the satisfaction of nursing career
      ladder system (NCLS) implementation. METHOD: A non-experimental survey design was
      used for this study. The respondents were selected using proportional random
      sampling technique with the total sample size of 149 nurses. Data were measured
      using proportion, central tendency and Pearson product-moment correlation.
      RESULTS: There was a moderate, positive correlation between the CPD and the NCLS
      satisfaction (R: 0.42, p= 0.0001). CONCLUSIONS: The results of this research
      should be used as recommendation for improving CPD at the hospitals in Indonesia.

PMID- 29650174
TI  - Improving the interpersonal competences of head nurses through Peplau's
      theoretical active learning approach.
AB  - BACKGROUND: Effective interpersonal skills are essential for head nurses in
      governing and managing their work units. Therefore, an active learning strategy
      could be the key to enhance the interpersonal competences of head nurses.
      PURPOSE: This study aimed to investigate the effects of Peplau's theoretical
      approach of active learning on the improvement of head nurses' interpersonal
      skills. METHOD: This study used a pre-experimental design with one group having
      pretests and posttests, without control group. A total sample of 25 head nurses
      from inpatient units of a wellknown private hospital in Jakarta was involved in
      the study. Data were analyzed using the paired t-test. RESULTS: The results
      showed a significant increase in head nurses' knowledge following the training to
      strengthen their interpersonal roles (P=.003). The results also revealed
      significant increases in the head nurses' skills in playing the roles of leader
      (P=.006), guardian (P=.014), and teacher/speaker (P=.015). Nonetheless, the
      results showed no significant increases in the head nurses' skills in playing the
      roles of counselor (P=.092) and stranger (P=.182). CONCLUSIONS AND
      RECOMMENDATIONS: Training in strengthening the interpersonal roles of head nurses
      significantly increased the head nurses' knowledge and skills. The results of the
      study suggested the continuation of active learning strategies to improve the
      interpersonal abilities of head nurses. Furthermore, these strategies could be
      used to build the abilities of head nurses in other managerial fields.

PMID- 29650175
TI  - Factors that affect the development of nurses' competencies: a systematic review.
AB  - OBJECTIVE: To investigate factors affecting the development of nursing competency
      based on a review of the literature. METHOD: A systematic review was utilized.
      The articles were taken from the databases of Pro-Quest, ScienceDirect,
      SpringerLink, and Scopus. They were retrieved using the following keywords:
      nursing competence, nurse competencies and clinical competence. Twenty-one papers
      were selected. RESULTS: Competence development is a continuous process of
      improving knowledge, attitudes and skills, and is influenced by a myriad of
      factors. Six factors were identified that affected the development of nursing
      competence in our systematic review: (1) work experience, (2) type of nursing
      environment, (3) educational level achieved, (4) adherence to professionalism,
      (5) critical thinking, and (6) personal factors. Work experience and education
      were shown to significantly influence the development of competency of nurses.
      CONCLUSIONS: Nurse managers need to support staffing competence through ongoing
      education, mentoring-preceptorship training, and case-reflection-discussion
      teaching programs.

PMID- 29650176
TI  - Pain-management strategies among hospitalized trauma patients: a preliminary
      study in a teaching hospital in Indonesia.
AB  - The incidence of trauma has been high and is considered to have increased
      throughout the years. This study aimed to describe the pain intensity and pain
      management strategies of hospitalized trauma patients. Ninety-five adults
      presenting trauma with full consciousness, and who were admitted to surgical
      wards were recruited. Outcomes were assessed in a 3-day follow-up of pain and
      pain management from January to February 2016 by using questionnaires for
      interviews. Data were analyzed using descriptive statistics and repeated measures
      ANOVA. Preliminary research found that hospitalized trauma patients perceived
      mild to severe pain intensity. The trend of pain at its worst, pain at its least,
      average pain, and current pain decreased from Day 1 to day 3, which were
      statistically and significantly different (p < .001). The pain management often
      used by patients were: praying (84.2%), slow and deep breathing (78.9%), and at
      an attempt at toleration (46.3%). The least frequent method of pain management
      included immediately informing nurses about the pain (15.8%), reading (15.8%),
      and changing position (17.9%). Besides the pharmacological and nonpharmacological
      interventions received from physicians and nurses, strategies were crucial to
      alleviating pain in hospitalized trauma patients related to cultural context.

PMID- 29650177
TI  - Validity and reliability of the Comfort Assessment Breast Cancer Instrument in
      breast cancer palliative care.
AB  - Indonesia is a developing country and most breast cancer patients present with
      terminal conditions, including discomfort. Comfort is a crucial component of
      nursing in palliative care, especially in breast cancer patients. However, this
      condition is difficult to assess and therefore assign as a diagnosis. Some
      comfort assessment tools have been developed in other countries are found not
      appropriate for an Indonesian context. This study is a sequence of prior
      qualitative research regarding a comfort assessment tool to be developed in
      Indonesia. This study piloted the comfort assessment tool in 55 patients with
      breast cancer to test if it is valid, reliable, and easy to use. This cross
      sectional study was conducted at an Army hospital in Jakarta, Indonesia. The
      Comfort Assessment Breast Cancer Instrument measured many aspect of the patient
      comfort level including physical, psycho-social, cultural-spiritual, finance, and
      environmental comfort using a Likert scale from 1-4 and 34 items. Data were
      processed using statistical software. The face validity test yielded coefficient
      a of 0.299-0.691, while the reliability test produced a reasonably good result as
      well (a = 0.912). Therefore this measure should be further assessed by an expert
      panel and including construct validity.

PMID- 29650178
TI  - The effective needle stick injury prevention strategies for nursing students in
      the clinical settings: a literature review.
AB  - OBJECTIVE: Nursing students are prone to needle stick injuries (NSIs) during
      their practice in the hospitals. This study aimed to identify the effective NSI
      prevention strategies for nursing students in the clinical settings. METHOD:
      Literature review was performed using the databases of ScienceDirect, ProQuest,
      MEDLINE, PsycINFO, Scopus, CINAHL, SpringerLink, JSTOR, and PubMed. The search
      terms of "nursing students", "NSI incidents", "prevention", and "clinical
      settings" were entered, generating 103 articles published between 1991 and 2015.
      RESULTS: Our study demonstrated the high rates of NSIs in low- and middle (India,
      91.85%). and high-income countries (Taiwan, 56.00%). Most injuries especially
      occurred when students opening the ampules (53.15%) and performing intravenous
      cannulation (44.50%). Our review identified four main strategies to prevent NSIs;
      education, trainings, safe needle use, and effective communication. Our study
      suggested the development of education and trainings curriculum and self- report
      system and culture, the provision of financial, material and manpower resources
      to support the prevention of NSIs. CONCLUSIONS: four main strategies to prevent
      NSIs were education, trainings, safe needle use and effective communication.
      IMPLICATIONS FOR PRACTICE: collaboration of hospitals and educational
      institutions is essential to develop effective NSI prevention programs.

PMID- 29650179
TI  - Mother-daugther communication about sexual and reproductive health issues in
      Singkawang, West Kalimantan, Indonesia.
AB  - While parent-adolescent sexual and reproductive health (SRH) communication is one
      potential source of information for adolescents, it appears to be inadequately
      practiced in Indonesia. Given that female adolescents in Indonesia are faced with
      increased sex-related risks, it is important to understand, from parents and
      adolescents' perspectives, how parents communicate about SRH to their
      adolescents. This study was designed to investigate parents and their female
      adolescent children's patterns of SRH communication in West Kalimantan,
      Indonesia. A total of 15 adolescent girls (ages 13-15) and 14 mothers took part
      in four focus group discussions. Fifteen girls, aged 13-15 and 14 mothers aged 25
      45 years participated in the study, sharing their reflections on their
      communication about sex and reproductive health issues. The analysis technique
      used was thematic analysis, which is performed by refining key themes that emerge
      from the data. Data were collected from the focus group discussions. The four
      themes identified in this study are: (1) Infrequent communication on sexuality
      between mothers and daughters, (2) Mothers' tendencies to avoid to discussing
      SRH, or feeling ashamed and that it is culturally unacceptable to talk about
      sexual matters, (3) Body change during puberty is the major content of the mother
      daughter communications, and (4) Both mothers and daughters need adequate
      information about SRH. The study reveals that communication regarding sexual and
      reproductive issues between parents and female adolescents is limited in
      Indonesia. The quality of communication on general topics between parents and
      their female adolescents is one of the important factors related to SRH
      communication between them. It is essential that Indonesian parents become better
      informed and skilled, so that they may be involved in the sexual and reproductive
      health education of their female adolescent children.

PMID- 29650180
TI  - Pain, stress, and sleep quality in chronic wound patients.
AB  - Chronic wounds are one impact of cancer cell growth that may cause discomforts or
      pain. This study aimed to identify the relationship between pain, stress, and
      sleep quality in cancer patients with a chronic wound. We used a cross-sectional
      design with 76 patients from a cancer hospital in Jakarta, Indonesia. The
      instruments used were the Numeric Rating Scale, the Questionnaire on Stress in
      Cancer Patients, Revised 23, and the Pittsburgh Sleep Quality Index. The results
      of this study showed that moderate-severe pain produced a higher than average
      amount of stress (58.86), while patients with no pain or only mild pain had a
      lower than average stress level (52.3). The results indicated that there was a
      relationship between pain before analgesic usage, pain during bandage
      replacement, pain that occurred at night, and stress (p=0.003, 0.007, and 0.002,
      respectively; alpha=0.05). Patients who had poor sleep quality experienced above
      average stress (56.3), while those with good sleep quality reported below average
      stress levels (45.6). These results indicated that there was a relationship
      between stress and sleep quality (p=0.033; alpha=0.05). Poor quality sleep is
      more common in patients with a moderate to severe pain scale rating (93.1%).
      However, Fisher's exact test results found that there was no relationship between
      pain and sleep quality (p=0.301; alpha=0.05). The results of this study concluded
      that stress can affect pain and sleep quality, but the pain did not have a direct
      effect on sleep quality in chronic wound patients.

PMID- 29650181
TI  - Relationship between levels of thyroid stimulating hormone, age, and gender, with
      symptoms of depression among patients with thyroid disorders as measured by the
      Depression Anxiety Stress Scale 21 (DASS-21).
AB  - OBJECTIVE: The aim of this study was to investigate the correlation between
      levels of depression symptoms and age, thyroid-stimulating hormone levels, and
      stressful life events of the participants. METHOD: Patients above 18 years old,
      with any thyroid disorders, and without psychiatric disorders were included in
      this study. All participants completed the Depression Anxiety Stress Scale 21
      (DASS-21). The depression symptom score was calculated and interpreted as
      follows: less than 9: no depression; between 10 and 13: mild depression; between
      14 and 20: moderate depression; between 21 and 27: severe depression, and more
      than 28: extremely severe depression. RESULTS: The total number of participants
      in this study was 199. There was no correlation between age, thyroid stimulating
      hormone, and the DASS score. There was also no significant difference in the DASS
      21 score between genders. However, there was a positive correlation between
      depression symptoms and stressful life events (r=0.201, n=199, p < 0.05).
      CONCLUSIONS: These findings would suggest that increased depression symptom
      scores correlate with increased stressful life events. A larger study should be
      undertaken to confirm these findings.

PMID- 29650182
TI  - Workplace violence against nurses in Indonesian emergency departments.
AB  - OBJECTIVE: The objective of this study was to examine the experiences of violent
      incidents by nurses in Indonesian emergency departments. METHOD: The World Health
      Organization's structured questionnaire on workplace violence in the health
      sector was modified and translated into Bahasa. The study participants were 169
      nurses working in emergency departments in six hospitals in Jakarta and Bekasi,
      Indonesia. The gathered data were analyzed using descriptive and multivariate
      logistic regression. RESULTS: Ten percent of emergency nurses reported
      experiencing physical violence, perpetrated mostly by patients, whereas more than
      half of emergency nurses (54.6%) reported experiencing non-physical violence,
      with patients' relative as the main perpetrators. A majority of nurses (55.6%)
      did not have encouragement to report workplace violence, and very few nurses
      (10.1%) had received any information or training about workplace violence.
      CONCLUSIONS: The findings of this study highlighted the seriousness of violence
      in Indonesian emergency departments. Support from management, encouragement to
      report violence, and access to workplace violence training were expected to
      mitigate and manage violence against nurses in emergency departments.

PMID- 29650183
TI  - The combination of nebulization and chest physiotherapy improved respiratory
      status in children with pneumonia.
AB  - OBJECTIVE: There is controversy regarding the effectiveness of chest
      physiotherapy to solve airway obstruction problems experienced by children
      younger than five years of age with pneumonia. The aim of this study was to
      determine the effectiveness of chest physiotherapy and nebulization on the
      respiratory status of these children. METHOD: This study was quasi-experimental
      with a pre- and post-test nonequivalent control group design. Thirty-four
      respondents selected by consecutive sampling were divided into two groups: one
      that received nebulization and one that received nebulization with chest
      physiotherapy. The independent t-test was used to analyze the effect of chest
      physiotherapy and nebulization on the respiratory status of children younger than
      age five with pneumonia. RESULTS: There was a significant mean difference in
      heart rate, respiratory rate, and oxygen saturation between the control and
      intervention group (p=0.000). Despite the correlation between age and heart rate,
      other characteristics (nutritional status, exclusive breast-feeding, vaccination,
      the length of illness, and the content of nebulization medication) had no effect
      on heart rate, respiratory rate, and oxygen saturation. CONCLUSIONS: The
      combination of nebulization and chest physiotherapy is more effective than
      nebulization only. It is important to reconsider the combination of nebulization
      and chest physiotherapy to overcome airway obstruction problems.

PMID- 29650184
TI  - Women's knowledge, beliefs, and behaviors toward the prevention of human
      papillomavirus transmission.
AB  - OBJECTIVE: To identify the relationship between women's knowledge, beliefs, and
      behaviors and human papillomavirus (HPV) transmission prevention. METHOD: This
      was a cross-sectional study with a convenience sampling technique. The samples
      were from 649 women of reproductive age who either were married or who had once
      been married. Data were analyzed using the Pearson and Spearman correlation
      tests. RESULTS: The results showed a statistically significant relationship
      between knowledge, beliefs and sexual behaviors, and the prevention of HPV
      transmission. Knowledge was the most dominant variable affecting the prevention
      of HPV transmission (r=0.174) with p value < 0.001; the better the women's
      knowledge, the higher the prevention effort. CONCLUSIONS: Beliefs regarding HPV
      transmission, healthy sexual behavior, and knowledge of prevention could reduce
      the prevalence of HPV transmission and would improve women's health in general.
      In addition, providing education, avoiding the risk factors, early detection, and
      performing a regular screening of reproductive organs are the key factors in
      preventing HPV transmission.

PMID- 29650185
TI  - Status disclosure and the acceptance of women living with HIV.
AB  - OBJECTIVE: This study aimed at identifying the acceptance of women living with
      HIV in relation to status disclosure. METHOD: This cross sectional study involved
      235 women with HIV positive in Public Health Centre in Jakarta, Indonesia, who
      were chosen with a consecutive sampling. We used a modified Acceptance of Disease
      and Impairments Questionnaire (ADIQ) as the instrument. RESULTS: The median score
      of acceptance was 3 (SD 0.72) in the range of 2.79 to 2.98 at 95% confidence
      interval. More than half of the respondent (65%) are housewives and 50% of them
      got infected from their spouses. It was also found that status disclosure was
      associated with the women acceptance towards HIV (p < 0.05) CONCLUSIONS: The
      acceptance of HIV-positive women is influenced by status disclosure which can be
      positive or negative. This study suggests nurses to consider the grief response
      of the women with HIV positive to facilitate their acceptance and better
      adaptation to the illness.

PMID- 29650186
TI  - The relationship of the preexisting anxiety problem with the demographic profile
      of cervical cancer patients.
AB  - OBJECTIVE: This study identified the association of the preexisting anxiety
      problem in women diagnosed with cervical cancer with their demographic
      characteristics. METHOD: This was a cross sectional study with 100 participants
      selected by purposive sampling method. Data were collected through Hamilton
      Anxiety Rating Scale (HARS) questionnaire and the medical records of
      participants. RESULTS: Work status was the only demographic characteristic which
      was found to be statistically significantly related to the anxiety level of the
      participants before they were diagnosed with cervical cancer. Participants who
      worked at home as housewives were found to have higher anxiety level than those
      worked at the institutions or industry. CONCLUSIONS: Working women in this study
      were more likely to have the preexisting anxiety problem prior their cervical
      cancer diagnosis. This study implies the importance of promoting healthy
      lifestyle to manage daily stressors, considering various interrelated factors
      that may eventually contribute to cervical cancer development in women.

PMID- 29650187
TI  - The influence of adolescent postpartum women's psychosocial condition on mother
      infant bonding.
AB  - OBJECTIVE: To identify the correlation between the psychosocial condition of
      adolescent women in the postpartum period and mother-infant bonding. METHOD: This
      study used a cross-sectional design. Using a consecutive sampling method, 103
      adolescent women with a 1- to 12-week-old baby were recruited. Participants
      completed the postpartum bonding questionnaire to identify mother-infant bonding.
      This questionnaire included four dimensions: the relationship between mother and
      baby, baby acceptance, readiness to perform maintenance, and delivery of comfort.
      RESULTS: We identified that 45.6% of the teen mothers in this study were at risk
      of psychosocial problems and that 67% of them had insufficient mother-infant
      bonding. There was a statistically significant correlation between the
      psychosocial condition of adolescent postpartum women and mother-infant bonding
      (p=0.000; OR=5.143; 95%CI, 0.195 to 135.662). CONCLUSIONS: Adolescent mothers
      require special attention during the perinatal period. They also require infant
      care education and preparation to become a successful mother. Maternity nurses
      play a very important role in providing education for adolescent mothers and the
      elderly. Maternity nursing services must be expanded to include psychosocial
      assessments for teen mothers throughout the pregnancy, childbirth, and postpartum
      periods.

PMID- 29650188
TI  - Oncology nurse reflection on the necessity of a pain assessment tool for
      Indonesian cancer patients.
AB  - OBJECTIVE: The purpose of this study was to obtain an overview on nurses'
      opinions and perceptions related to pain assessment and other problems
      experienced in evaluating pain in cancer patients. METHOD: This descriptive
      qualitative study was part of a series of studies to develop a pain assessment
      tool for cancer patients in Indonesia. Data were collected by semi-structured
      interviews from 16 oncology nurses. A cross-case comparison of the interview
      responses was used to analyze the data from verbatim interview transcripts.
      RESULTS: Six themes were identified: pain as the main complaint reported by
      cancer patients; pain assessment using a pain scale; an awareness of the absence
      of nurses' role in pain management; a lack of understanding of pain conditions;
      acknowledgement that a pain assessment tool should be practical and user
      friendly; and the need to develop a pain assessment tool. We also explored the
      knowledge of nurses in pain management and achieved an in-depth understanding of
      the nurses' desire to seek additional knowledge related to pain assessment.
      CONCLUSIONS: A pain assessment tool should be developed to assist nurses to
      independently interpret data about pain and allow them to select or modify
      interventions consistent with the patients' needs. Pain management for cancer
      patients is one of the essential nurses' responsibilities in providing
      comprehensive meaningful nursing care.

PMID- 29650189
TI  - Islamic moral judgement on abortion and its nursing applications: expository
      analysis.
AB  - Health workers, like nurses are tasked to save the lives of their patients,
      however, there are instances in which health workers have to deal with difficult
      cases in taking a life, such as abortion. Scholars in the field of healthcare
      assert that abortion is morally justified if it is sought for health reasons.
      Nevertheless, there are a number of cases in which abortion is sought on other
      grounds other than health, such as the individual choice to do so. Can a nurse
      refuse to provide their professional service towards these people? This paper
      uses analytical and comparative methods to address ethical issues in abortion
      from the Islamic and conventional perspectives. Nursing implication: Since the
      nurses instruct and assist people in forming a decision as they engage in nursing
      care, utilising a comprehensive view of abortion based on Islamic sources would
      provide a foundation in Muslim perspectives as they interact with Muslim
      patients. The subject area to investigate the degree of knowledge among nurses
      regarding the Islamic moral judgement on this event is extremely recommended for
      future management.

PMID- 29650190
TI  - Improving the utilization of health services among high-risk pregnant women
      through community health nurse assistance.
AB  - OBJECTIVE: The objective of this study was to identify the impact of implementing
      community health nurse assistance for high-risk pregnant women on utilization of
      health services. METHOD: The study was quasi experimental with a control group
      design. The sample included high-risk pregnant women in 10 community health
      centers in Indonesia who were selected by consecutive sampling. The total sample
      included 66 women in both the intervention and the control groups. The high-risk
      pregnant women in the intervention group received nurses' assistance during the
      third trimester and until giving birth. Before and after the intervention, the
      knowledge, attitudes, and behavior of the women were measured. RESULTS: The
      average scores for the knowledge, attitudes, and behavior of women in the
      intervention group increased. Differences were found in health care utilization
      between the two groups. All women in the intervention group received antenatal
      care during the third trimester more than once and were assisted by skilled
      health personnel during childbirth, while in the control group 10.6% of
      respondents were assisted by a paraji shaman (traditional birth attendant). All
      women in the intervention group accepted family planning, and the contraceptive
      choice varied. CONCLUSIONS: The assistance of community health nurses improves
      the knowledge, attitudes, and behavior of high-risk pregnant women and positively
      impacts the rate of health care utilization.

PMID- 29650191
TI  - Supportive care needs and quality of life of patients with gynecological cancer
      undergoing therapy.
AB  - OBJECTIVE: To identify the relationship of unmet supportive care needs with
      quality of life of patients with gynecological cancer undergoing therapy. METHOD:
      This study used a cross-sectional design. A total of 153 patients with
      gynecological cancer undergoing therapy were recruited using consecutive sampling
      methods. The participants completed the questionnaire of Supportive Care Needs
      Survey to identify their supportive care needs, EORTC-QLQ 30 to assess their
      general quality of life, and EORTC-QLQ-CX 24 or - OV 28 to determine cancer
      specific quality of life in cervical cancer and ovarian cancer, respectively.
      RESULTS: Most of the participants (96.1%) reported their unmet needs of
      supportive care predominantly in the physical domain (80.4%). Unmet supportive
      care needs were found to be statistically significantly related to quality of
      life in the global health, functional, and symptom domains (p value 1=0.003, p
      value 2=<0.001, and p value 3= 0.001; r1=-0.235, r2=0.306, and r3=0.268,
      respectively). CONCLUSIONS: Patients with gynecological cancer needs various
      supportive care during treatment. These supportive care needs should be
      identified early at the time of diagnosis and continued throughout the disease
      and treatment trajectory to the survivorship point. Otherwise, unmet supportive
      care needs may lead to a low quality of life.

PMID- 29650192
TI  - Family support and maternal self-efficacy of adolescent mothers.
AB  - OBJECTIVE: To identify a correlation between family support and maternal self
      efficacy of adolescent mothers. METHOD: This cross-sectional study applied a
      consecutive sampling technique. The sample was 100 primiparous adolescent
      mothers. Instruments utilized were structured questionnaires, including a
      demographic questionnaire, Maternal Efficacy Questionnaire (MEQ), Postpartum
      Support System, Edinburgh Postnatal Depression Scale (EPDS), and Infant
      Characteristics Questionnaire (ICQ). The correlation of family support and
      maternal self-efficacy was analyzed using chi-square and logistic regression.
      RESULTS: The results showed a significant correlation between family support and
      maternal self-efficacy of adolescent mothers. The family support that most
      influenced maternal self-efficacy of adolescent mothers was family instrument
      support, with Wald value of 34.720. CONCLUSIONS: Instrument support most affects
      maternal self-efficacy of adolescent mothers and encourages adolescents
      performing nurturing and mothering roles.

PMID- 29650193
TI  - Inhalation with bronchodilator combination effective in reducing length of
      hospital stay in children with pneumonia.
AB  - OBJECTIVE: This study aimed to examine the correlation between inhalation therapy
      and length of hospital stay in children under age of five with pneumonia. METHOD:
      This cross-sectional study included 102 consecutive patients (secondary data)
      with pneumonia. The patients were divided depending on the type of therapy they
      received: Group I used inhalation therapy with bronchodilator beta-agonist + NaCl
      0,9%, Group II used inhalation therapy with bronchodilator beta-agonist and
      anticholinergic + NaCl 0,9%, Group III used inhalation therapy with NaCl 0,9%,
      and Group IV used no inhalation therapy. RESULTS: The study results showed a
      significant correlation between the use of inhalation therapy and the length of
      hospital stay (p = 0.000) after being controlled age, leucocyte count, and the
      type of antibiotic therapy. However, there was no significant correlation between
      the use of inhalation therapy and the length of hospital stay in children under
      the age of five with pneumonia after sex and oxygen therapy being controlled.
      CONCLUSIONS: Inhalation therapy with a combination of bronchodilator beta-agonist
      and anticholinergic + NaCl 0.9% and with bronchodilator beta-agonist + NaCl 0.9%
      are the two most effective treatments with which to reduce the length of hospital
      stay in toddlers with pneumonia.

PMID- 29650194
TI  - Fracture risk prediction in post-menopausal women with osteopenia and
      osteoporosis: preliminary findings.
AB  - OBJECTIVE: The study aims to identify the risk of obtaining a fracture among post
      menopausal women with osteopenia and osteoporosis. METHOD: This work was a cross
      sectional study involving a purposive sample of 87 post-menopausal women who
      attended the orthopedic and menopause clinics of Hospital Tengku Ampuan Afzan,
      Kuantan. The data were entered into the WHO fracture risk assessment tool
      (FRAX(r)) to predict major fracture and risk for hip fracture in 10 years' time.
      RESULTS: The mean age of the respondents was 61.6 years (SD=7.9). Among the
      respondents, 50.6% had osteopenia and nearly half (48.3%) had osteoporosis. The
      mean number of menopausal years of the respondents was 11.9 (SD=8.5), ranging
      between 1 and 44 years. The FRAX findings indicated 9.7% major osteoporotic
      fracture probability and 3.5% hip fracture probability, which were denoted as
      high risk. A Pearson correlation coefficient was computed to assess the
      relationship between menopausal years and the FRAX major osteoporotic fracture
      probability. A significant positive correlation was found between the two, but
      the correlation was weak (r=0.581, n=87, p < 0.001). CONCLUSIONS: The present
      findings indicate that menopausal years have a positive correlation with the risk
      of obtaining a fracture.

PMID- 29650195
TI  - Student perception of interprofessional education application at the Health
      Sciences University of Sumatera Utara.
AB  - OBJECTIVE: Interprofessional education (IPE) includes collaborative
      interprofessional learning activities involving students and lecturers from the
      health sciences faculties at the University of Sumatera Utara. This descriptive
      study aimed to explore the students' perceptions of the application of the IPE
      program. METHOD: Descriptive study was conducted and one hundred sixty students
      were selected from four faculties including the faculties of medicine, nursing,
      pharmacy, and public health. RESULTS: The results of the study showed that 68% of
      the participants stated that they had heard IPE information, whereas 97% reported
      that they had never joined in IPE activities. In the health sciences faculties,
      57% of nursing students had heard IPE information, but more than 90% of the
      participants from the other faculties had never heard the IPE information. Also,
      based on aspects of their participation, all of the students reported that they
      had never joined in the IPE activities. CONCLUSIONS: according the results, the
      implementation of IPE can be realized in the integration of learning methods,
      such as lectures, practicum, clinical skills, and tutorials. It can be a
      university policy so that the implementation of IPE with specific learning
      methods can take place to improve the competence of collaboration students.

PMID- 29650197
TI  - Family support in caring for older people with diabetes mellitus: a phenomenology
      study.
AB  - OBJECTIVE: This study was conducted to gain a deep understanding of the
      experience of older people with diabetes mellitus (DM) about their family support
      in Tasikmalaya, Indonesia. METHOD: The qualitative design was used with a
      phenomenological approach. Data were collected through in-depth semi-structured
      interviews of eight older people with DM. Ethical clearance was obtained from The
      Ethics Committee of the Faculty of Nursing, University of Indonesia. All the
      participants were provided with information about the purpose and the type of the
      study. Participants' type of participation in this research was voluntary. The
      recorded interviews were reported anonymously. Data were analyzed using the seven
      steps of Colaizzi include reading the transcript, listening to the transcript,
      choosing keywords, categorizing grouping, creating narratives, validating, and
      translating findings into a complete narrative. RESULTS: Three themes were
      identified about family support toward older people with DM such as the changes
      in older people with DM, optimum family support and suboptimal family support.
      CONCLUSIONS: The physical and psychological changes which older people with DM
      had experienced affect the family support they had received. Therefore, this
      study will give a valuable contribution to the improvement of health service for
      older people with DM in Indonesia.

PMID- 29650196
TI  - Clinical care pathway strenghens interprofessional collaboration and quality of
      health service: a literature review.
AB  - OBJECTIVE: To review the effectiveness of a clinical care pathway on
      interprofessional collaboration and quality of health service. METHOD: A review
      was performed of literature published from 2000 to 2015, with the following
      keywords: clinical pathway, care pathway, and interprofessional collaboration.
      RESULTS: Evidence depicted the positive results of nursing care for clients,
      health care professionals and facilities. The research results were implemented
      at different facilities using several research designs, from descriptive to
      experimental. A clinical pathway was used as a tool in various clinical
      situations including in emergency, elective surgery, and pre-post-surgery, as
      well as in common clinical cases. It was administered by the health care
      professionals in providing care, encompassing the comprehensive process from
      diagnosis to clinical audit. Health care professionals should engage in active
      collaboration during the implementation of a clinical care pathway. In
      implementing the standard of input, process, and outcome of care to clients,
      health care professionals should emphasize the process and outcome of care and
      eliminate unnecessary or inefficient treatments. CONCLUSIONS: A clinical care
      pathway could reduce the average length of stay for patients, increase cost
      effectiveness, and, consequently, improve the quality of service. To optimize the
      care process, the pathway should be implemented of multidisciplinary health care
      team.

PMID- 29650198
TI  - Analysis on the implementation of a health improvement project (Garbage Clinical
      Insurance) in Indonesia: a literature review.
AB  - OBJECTIVE: Indonesia Medika has established "Garbage Clinical Insurance" (GCI),
      which enables the population below the poverty line (BPL) to obtain health
      insurance by donating their garbage to pay the premium. The objective of this
      paper was to critically examine the implementation of GCI in Indonesia by
      reviewing the background, effects, and sustainability of this program. METHOD: A
      literature search of studies related to GCI, other types of micro health
      insurance, and their applications in developing countries was conducted. Recent
      news (post 2014) related with the implementation of GCI was also consulted.
      RESULTS: The literature revealed that the foundation of GCI was informed by the
      Declaration of Alma Ata with the ideal of making health care services accessible
      to everyone. Unlike most health insurance, the mechanisms of GCI seem less likely
      to trigger moral hazard among its beneficiaries. However, as a micro insurance
      program, the sustainability of GCI continues to be called into question.
      CONCLUSIONS: The critical analysis of the present study has highlighted the
      application of GCI, a micro health insurance initiative, and its relevance to
      Indonesia. GCI tended to work well as it was able to utilise Indonesia's social
      capital. However, GCI should aim to increase the benefits package available to
      its members in order to maintain the sustainability of the program.

PMID- 29650199
TI  - Preventing Pasung by mentally ill patients' families.
AB  - Pasung is a way of handling the mentally ill in the several Indonesian
      communities. In many cases, when the patients leave the hospital they are once
      again turned out by their families and returned to the pasung. This study aims to
      identify and explore the means of preventing mentally ill patients in the
      community from being subjected to pasung through a test of Daulima's Pasung
      Decision Questionnaire that measures a family's intention to use pasung. This
      study tested the content validity and reliability of Daulima's Pasung Decision
      Questionnaire by using the Spearman-Brown single test-single trial. The
      respondents were 300 people drawn from five provinces in Indonesia: West Sumatra,
      East Kalimantan, West Nusa Tenggara, West Java and the Special Capital Region of
      Jakarta. The validity and reliability results showed that the content of this
      instrument is valid once improvements had been made to the statement items
      numbers 16 and 17. It was also shown to be reliable by the consistency of the
      responses with an alpha value of 0.729. This means that responses to the
      instrument are consistent and are reliable measures of the level of intention of
      the mentally ill patient's family to use pasung.

PMID- 29650200
TI  - Arbi Care application increases preschool children's hand-washing self-efficacy
      among preschool children.
AB  - OBJECTIVE: This research aimed to examine the effectiveness of an Android mobile
      game application called Arbi Care as a means to prevent diarrhea and build self
      efficacy in hand washing among preschool children. METHOD: This research used a
      pre- and post-test control group and time series design approach. Respondents
      were chosen randomly from a group of four to six years children. The intervention
      group (n = 60) received Arbi Care intervention for 25 minutes, twice a week, for
      five weeks while the control group (n = 60) received standard education. Self
      efficacy was measured by using questionnaire and observation. Measurement was
      carried out three times in the sixth, eight, and tenth week post-intervention.
      The data was analyzed using the GLMRM test. RESULTS: There was a significant
      increase in the average score of self-efficacy in hand washing for the
      intervention group versus the control group. Moreover, there were significant
      differences in the results of average scores in which the intervention group
      showed much better self-efficacy improvement over the control group during the
      first, second, and final post-test after the intervention was given (p < 0.001).
      CONCLUSIONS: An Android-based educational game can be an effective medium to
      improve hand washing self-efficacy among preschool children, thus helping to
      prevent diarrhea.

PMID- 29650201
TI  - Spirituality in adolescents with cancer.
AB  - OBJECTIVE: As adolescents with cancer are at risk of experiencing spiritual
      distress, they tend to have unique spiritual needs. Spirituality plays a
      significant role for adolescents with cancer as it contributes to increased
      comfort and calmness, and better coping mechanisms when confronted with the
      illness, which indirectly improves the adolescent's quality of life. This study
      aimed to explore spiritual experiences in adolescents with cancer. METHOD: A
      qualitative study using a phenomenology approach was conducted. Nine adolescents
      with chemotherapy-treated cancer were purposefully selected to be involved in
      this study. The data were analyzed using thematic analysis. RESULTS: This study
      identified six spiritual themes in adolescents with cancer: a) accepting their
      illness; b) believing their illness in God's will; c) improving spiritual
      practices; d) expressing empathy to parents; e) maintaining relationships with
      significant others, and f) achieving self-actualization. CONCLUSIONS: This study
      demonstrated that spirituality gave hope to adolescents by helping them to
      overcome existential problems related to cancer. We believe it is necessary for
      nurses to address the spiritual needs of adolescent with cancer as this will help
      these young people accept their condition with more grace and humility.

PMID- 29650202
TI  - Impact of family empowerment model on satisfaction and children's length of stay
      in hospital.
AB  - OBJECTIVE: The purpose of the study was to identify the impact of family
      empowerment model intervention on family satisfaction and children's length of
      stay in the hospital due to pneumonia. METHOD: The design of the study was that
      of a quasi-experiment. About 83 family-child groups were divided into 42 pair in
      the intervention group and 41 pair in the control group; which were recruited
      using consecutive sampling using certain inclusion criteria. Three district
      hospitals in Jakarta were used in this study. A questionnaire and family
      empowerment instrument were developed and used to collect the data. An analysis
      of the data used independent and paired t-test. RESULTS: The results of the study
      showed a significant difference between the intervention and control groups in
      empowerment and satisfaction aspects after the intervention (p= 0.000; p= 0.000).
      An analysis of length of stay using the t-test indicates a significant difference
      between the intervention and control groups (p= 0.000). CONCLUSIONS: The family
      empowerment model (FEM) intervention has a positive impact on families, as it can
      increase both the satisfaction and the empowerment of the family. Another
      important indicator of the FEM's success is its ability to decrease the length of
      stay of patients.

PMID- 29650203
TI  - Do adolescent cancer survivors need health care and psychosocial services?: An
      Indonesian experience.
AB  - OBJECTIVE: Advances in childhood cancer treatment have contributed to an
      increased survival rate among childhood cancer patients. The increasing number of
      survivors means that more help is needed to support them in dealing with the
      physical and psychosocial problems following their cancer therapy. This study
      explored the needs of adolescent cancer survivors in terms of health care and
      psychosocial services. METHOD: This qualitative research used a phenomenological
      approach. Eight adolescent cancer survivors were interviewed using a semi
      structured format. The data were analyzed using a thematic analysis. RESULTS:
      Seven themes emerged from the study results: (i) follow-up care; (ii) education
      for patients and their families; (iii) compassionate health care services; (iv)
      psychological counseling; (v) support from families and friends; (vi) support
      from school; and (vii) support from social community activities. CONCLUSIONS:
      These findings showed that adolescent cancer survivors in Indonesia need long
      term follow-up care for their physical and psychosocial needs. Nurses should play
      an active role in addressing the needs of adolescent cancer survivors as
      described in this study.

PMID- 29650204
TI  - Pacifier and swaddling effective in impeding premature infant's pain score and
      heart rate.
AB  - OBJECTIVE: To assess the effectiveness of pacifier and swaddling on premature
      infant's pain score, hearthrate, and oxygen saturation during an invasive
      procedure. METHOD: This randomized control trial involv 30 premature infants who
      were randomly assigned into control (n=15) and intervention (n=15) groups using
      parallel design. Infants in the intervention group received pacifier and
      swaddling when they were undergoing invasive procedures. The outcome indicators
      of the two-day intervention were pain score, hearth rate, and oxygen saturation.
      The Premature Infant Pain Profile (PIPP) was used in this study to measure
      infants' pain. RESULTS: The paired t-test results showed that the pain score and
      heart rate were significantly increased following the procedure in the control
      group (p=0.003; p=0.013 < 0.05); meanwhile, there was no significant increase in
      the intervention group (p=0.256; p=0.783 > 0.005). There was no significant
      different in oxygen saturation in the control group (p=0.270) and in the
      intervention (p=0.370) group before and after the procedure. CONCLUSIONS:
      Providing pacifier and swaddling can impede the increase of premature infants'
      pain score and hearth rate during an invasive procedures, therefore it can be
      implemented as an alternative to pain management in premature infants.

PMID- 29650205
TI  - Chewing gum is more effective than saline-solution gargling for reducing oral
      mucositis.
AB  - OBJECTIVE: This quasi-experimental study compared the effectiveness of chewing
      gum and gargling with a saline solution as two types of intervention to reduce
      oral mucositis scores. METHOD: The sample consisted of 44 children who were
      divided into two groups, one of which chewed gum, and the other gargled with a
      saline solution. The Mann-Whitney U test was used to analyze the data. RESULTS:
      There was a significant difference (p = 0.001) in post-intervention oral
      mucositis scores. The significant mean difference between the groups indicated
      that the decreased oral mucositis scores for the chewing gum group was more
      substantial than for the group gargling with a saline solution (p = 0.001).
      CONCLUSIONS: The data showed that chewing gum is more effective than gargling
      with a saline solution, and it can be incorporated into the nursing protocol for
      treating pediatric cancer patients.

PMID- 29650206
TI  - Correlation between parent-adolescent communication and adolescents' premarital
      sex risk.
AB  - OBJECTIVE: Previous studies have indicated the parent-adolescent relationship has
      a correlation to adolescents' premarital sex behavior risk. Therefore, the aim of
      this study was to discover the influence of parent-adolescent communication on
      adolescents' risk of sexual issues. METHOD: This was a quantitative study with a
      cross-sectional design. The population of this study consisted of students from a
      high school in Jakarta. A purposive sampling technique was used, which resulted
      in the selection of 253 students as samples. A PACS (Parent-Adolescent
      Communication Scale) questionnaire was applied. RESULTS: The results showed that
      59.3% of the adolescents studied were at risk for engaging in premarital sex,
      while the risk for adolescents with positive communication with their parents was
      56.5%. Bivariate analysis also showed a significant correlation between gender
      and parent-adolescent communication and the risk of adolescent premarital sex
      behavior (alpha < 0.05). This study's result was expected, and nurses can follow
      up by providing health education on how to maintain good communication between
      parents and adolescents. CONCLUSIONS: Communication must align with adolescents'
      developmental tasks. Nurses can also create a promotion program on the topic of
      communication for parents and adolescents.

PMID- 29650207
TI  - The effect of a community-based spiritual life review program on Indonesian
      elders' resilience.
AB  - OBJECTIVE: This quasi-experimental, pre-/post-test study aimed to examine the
      effect of a community-based spiritual life review program on the resilience of
      elders residing in a disaster-prone area. METHOD: Fifty-two participants who met
      the inclusion criteria were recruited from three villages in the Kutaraja sub
      district in Banda Aceh, Indonesia. The participants were randomly assigned to an
      experimental group and a control group. The participants' names were listed and
      then randomly selected by a random number generator. The experimental group
      underwent a community-based spiritual life review program, which included a
      review of their spiritual lives, the appreciation of feelings, affirmation by the
      religious leader, a reevaluation of their lives, and a reconstruction of their
      lives to recognize their memories and present feelings. RESULTS: The elderly
      resilience scores were evaluated four weeks after the program was implemented.
      The control group received the same program after the study was finished. The
      participants in the experimental group significantly improved their resilience
      levels after completing the program (p < .05). There was a slight increase in the
      resilience scores from the pre-test to the post-test in the experimental group
      compared with the control group (p < .05). CONCLUSIONS: Future studies should add
      implementation sessions and avoid photos that would induce participants'
      traumatic memories or experiences during the spiritual life review.

PMID- 29650208
TI  - Walking and talking activities as nursing therapy for improving quality of life
      among older adults.
AB  - OBJECTIVE: The most prominent problem resulting from decreased body function in
      older adults is declining quality of life. Walking and talking among older adults
      in peer group may become a nursing therapy to improve their quality of life. The
      objective of this study was to identify the impact of walking and talking
      intervention of quality of life among community dwelling older adults in Depok,
      Indonesia. METHOD: This study applied quasi-experimental design with 43 and 40
      older adults in the intervention and control group, respectively. The
      participants were selected using multistage random sampling method. RESULTS:
      Based on t test, the average quality of life score of older adults improved more
      significantly in the intervention group than that in the control group, with p
      value of 0.003, its mean p value < alpha, respectively. An ANCOVA analysis was
      used to detect confounding factors. The result showed that all characteristics
      have a p value of > 0.05, which means there were no confounding factors
      warranting further investigation. CONCLUSIONS: It was concluded that walking and
      talking therapy in peer group significantly increase the quality of life of older
      adults.

PMID- 29650209
TI  - Reducing neglect and improving social support for older people following a self
      help group in the poor urban community of Jakarta, Indonesia.
AB  - Increasing age has an impact on the decline of organ function and results in
      increasing dependence on others, including family. Efforts must be made to
      increase older adult's' independence to help them overcome naturally occurring
      changes and health problems. This research aims to determine the effects of the
      self-help groups as nursing interventions using guidelines of selfhealth
      monitoring and management on the incidence of neglecting and the social support
      of older people. A quasi-experimental design was used on a total sample of 208
      people, consisting of 103 in the intervention group and 105 in the control group.
      An independent t-test was conducted before and after the intervention model to
      analyze the social support variable, and chi-square test was applied to analysis
      the neglect variable. The results showed the effects on the incidence of neglect
      of older people, and there were significant differences between and within the
      intervention and control groups (p < 0.05) in terms of social support. The
      intervention model demonstrated reduction of the incidence of neglect and an
      increase in social support. The results indicate that this program can be used as
      a guideline for health care center nurses in fostering self-help groups for older
      people in the community.

PMID- 29650210
TI  - The effects of chair yoga with spiritual intervention on the functional status of
      older adults.
AB  - OBJECTIVE: "Functional status" is an individual's ability to fulfill his/her
      needs and to perform the activities of daily life independently. Functional
      decline can lead to a higher level of dependency. This study aims to investigate
      the effects of chair yoga with spiritual intervention on the functional status of
      older adults. METHOD: This quasi-experimental study employed a pre- and post-test
      design using a control group. The study involved an intervention group of 42
      respondents and a control group of a further 42 respondents. The sample was
      selected using multistage random sampling. The data were analyzed using a t-test.
      RESULTS: The results of the study show that the mean score for the intervention
      group was higher after the intervention (p=0.000). Furthermore, the mean score
      for functional status after the intervention was significantly higher for the
      intervention group than for the control group (p=0.000). CONCLUSIONS: It is
      concluded that the use of chair yoga with spiritual intervention is a useful
      preventive measure against functional decline in older adults. The study also
      suggests that this form of intervention should be considered as a complementary
      nursing therapeutic practice for older adults in the community.

PMID- 29650211
TI  - Relationship between the levels of family burden in caring for older people with
      the incidence of mistreatment.
AB  - BACKGROUND: Caring for older people can be a burden for the family that led to
      mistreatment. OBJECTIVE: To determine the relationship between the levels of
      family burden in caring for older people with the occurrence of mistreatment
      incidence. DESIGN AND PARTICIPANTS: A cross sectional study design was conducted
      with 135 older people who live with their family as respondents. SETTING: 135
      families with older people at Kelurahan/Village of Harjamukti area, Kecamatan/
      District of Cimanggis, Depok city. METHOD: This study applied probability
      sampling technique with multistage cluster sampling. RESULTS: Family
      characteristics show that almost half of older people were caring by family
      members (caregivers) who were aged 20-39 years, nearly all caregivers were women,
      family income mostly less than UMK, families mostly monosyllabic nation Betawi
      and caregivers mostly were their own child. Most of the families stated that no
      expense in caring for the older people (89.6%), but there are still families who
      feel the burden of caring. The highest type of mistreatmet of the older people is
      psychological mistreatments. CONCLUSIONS: From the statistical test obtained by p
      value equals to 0.553, it was concluded there was no correlation between the
      incidences of any family burden with mistreatment.

PMID- 29650212
TI  - The experience of older people living in an elderly residential home (Panti
      Sosial Tresna Werdha): a phenomenology.
AB  - OBJECTIVE: The aim of this study was to gain an overview of the experiences of
      older people living in an elderly residential home (Panti Sosial Tresna Werdha
      [PSTW]). METHOD: The study used qualitative method with the descriptive
      phenomenology approach. The participants consisted of six older people who live
      in institutions. Data were collected through in-depth interviews in accordance
      with the purpose of the research, and an analysis of the data from the interviews
      was performed using the analysis stage by Collaizi. RESULTS: Three themes emerged
      from this study, namely independent living needs and support systems as a reason
      for staying at PSTW, the adaptive response to life in PSTW, and family support as
      a contributing factor to remaining at PSTW. CONCLUSIONS: Most of the elderly's
      support came from their children or nephews and nieces. Receiving full emotional
      support from relatives through family visits was deemed necessary for the
      elderly, as it made them feel happy to continue the rest of their lives in the
      elderly care home.

PMID- 29650213
TI  - The experience of adolescents having mentally ill parents with pasung.
AB  - OBJECTIVE: Lack of knowledge and powerlessness make family restrains, chains or
      confines (pasung) the family member with mental illness. This study aimed to
      explore the experience of adolescents having mentally ill parents with pasung.
      METHOD: To achieve detailed and accurate understandings of adolescents'
      experiences, this study used a qualitative research design with a
      phenomenological approach. Purposive sampling was employed to find teenagers aged
      12-19 years old who had mentally ill parents with pasung. The data were analyzed
      with Colaizzi's method. RESULTS: Parents with mental illness, specifically with
      physical restrain and confinement (pasung) had psychosocial impact on
      adolescents. Role changes often occur in the family where teenagers should be a
      breadwinner and caregiver for their parents. The results of this study were
      described in three themes: 1) changes of life due to have mentally ill parents
      with pasung; 2) reciprocity as the reason for taking care of the parents; 3)
      positive meaning of living with mentally ill parents with pasung. CONCLUSIONS:
      This study concludes that psychosocial treatment for adolescents living with
      parents with pasung should consider the psychological and social impact as a
      result of taking care of their parents with pasung.

PMID- 29650214
TI  - Acceptance and commitment therapy and family psycho education for clients with
      schizophrenia.
AB  - OBJECTIVE: This study aims to determine the effectiveness of combining acceptance
      and commitment therapy with family psycho education on increased insight,
      diminished symptoms, and the client's improved ability to control violent
      behavior. METHOD: The design of this study was a quasi-experimental pretest
      posttest utilizing intervention and control groups. The intervention group
      consisted of 33 people, and the control group was composed of 33 people. Data was
      collected before and after respondents received both acceptance and commitment
      therapy and family psycho education. RESULTS: The study showed that patient
      insight improved significantly, the signs and symptoms of violent behavior
      decreased, and the client's ability to control such behavior improved with a p
      value < 0.05 in the intervention group after they received acceptance and
      commitment therapy and family psycho education. In the control group, patient
      insight did not improved significantly, showing a p value > 0.05. Therefore, our
      study recommends that acceptance and commitment therapy and family psycho
      education should be given to patients with schizophrenia to improve insight into
      their disease, decrease signs and symptoms of violent behavior and improve their
      ability to control violent behavior.

PMID- 29650215
TI  - Do different positions affect the oxygen saturation and comfort level of children
      under five with pneumonia?
AB  - OBJECTIVE: Children with pneumonia need a correct position to increase their
      oxygen saturation and comfort level. Postural changes affect the function of the
      human body and disease conditions. This study aimed to identify the effect of
      prone and semirecumbent positions on the oxygen saturation and comfort level of
      children under five with pneumonia. METHOD: The study design was a quasi
      experimental with a pre-posttest control group design. Thirty-six children with
      pneumonia aged 0-59 months were selected using consecutive sampling and divided
      into three groups: prone (n = 12), semirecumbent (n = 12), and control (n = 12).
      Statistical analysis was conducted using the Wilcoxon test, paired t test, and
      Kruskal-Wallis test. RESULTS: A significant difference in the oxygen saturation
      level was found among the three groups, particularly in the semirecumbent group.
      No significant difference was observed on the comfort level in all groups.
      CONCLUSIONS: The semirecumbent position can be applied to improve the oxygenation
      status of children under five with pneumonia. Therefore, nurses should teach the
      family how to position the children with pneumonia during their hospitalization.

PMID- 29650216
TI  - The effectiveness of acceptance and commitment therapy on anxiety in clients with
      stroke.
AB  - OBJECTIVE: The purpose of this study was to determine the effects of acceptance
      and commitment therapy on anxiety in patients with stroke, especially during the
      first stage of recovery. METHOD: This quantitative study featured a quasi
      experimental design without a control group and was conducted in the stroke ward
      of a public hospital. The 33 respondents were selected via consecutive sampling.
      The data analysis was completed using the paired t-test. RESULTS: The use of
      acceptance and commitment therapy significantly the signs and symptoms of anxiety
      in patients with stroke (p-value = < 0.005). Specifically, acceptance and
      commitment therapy effectively decreases anxiety levels from a moderate level to
      a mild level in clients who are recovering from stroke. CONCLUSIONS: Acceptance
      and commitment therapy is a recommended treatment for reducing anxiety in stroke
      patients. The design of this study can be further developed to include a control
      group.

PMID- 29650217
TI  - Effect of logo-therapy, acceptance, commitment therapy, family psychoeducation on
      self-stigma, and depression on housewives living with HIV/AIDS.
AB  - OBJECTIVE: Self-stigma in people living with HIV/AIDS is a survival mechanism to
      protect themselves from external stigma. Stigma and discrimination in people
      living with HIV/AIDS can lead to inequality in social life. This inequality can
      cause inferiority complex, preoccupation, and denial of diagnosis, which
      correlates with the onset of depression. This study aims to determine the effect
      of logotherapy, commitment acceptance therapy, and family psychoeducation on self
      stigma and depression on housewives living with HIV/AIDS. METHOD: This study used
      the quasi-experiment pretest-posttest design. The respondents were selected using
      the purposive sampling technique. The subjects were 60 housewives living with
      HIV/AIDS. Data were collected using Internalizes Stigma of AIDS Tools and
      analyzed using univariate and bivariate analyses. Equality analysis was conducted
      using the chi-square test and independent t test, and the effects were analyzed
      using paired t test. RESULTS: The result showed a significant decrease in self
      stigma and depression (p value < 0.05) in patients receiving logotherapy,
      commitment acceptance therapy, and family psychoeducation. CONCLUSIONS: A
      combination of logotherapy, commitment acceptance therapy, and family
      psychoeducation is recommended as a therapy package to overcome self-stigma and
      depression for people living with HIV/AIDS.

PMID- 29650218
TI  - Corrigendum to 'Development of a mechanistic biokinetic model for hepatic bile
      acid handling to predict possible cholestatic effects of drugs' [European Journal
      of Pharmaceutical Sciences 115 (2018) 175-184].

PMID- 29650219
TI  - WITHDRAWN: Cytogenetics alteration in adult men involved in the recycling of
      electronic wastes.

PMID- 29650220
TI  - Urban Teledermatology: Concept, Advantages, and Disadvantages.

PMID- 29650221
TI  - Lymph Node Dissection in Patients With Melanoma and Sentinel Lymph Node
      Metastasis: An Updated, Evidence-Based Decision Algorithm.
AB  - Recent publication of the results of clinical trials in which lymph node
      dissection was not associated with any survival benefit in patients with sentinel
      node metastasis makes it necessary to reconsider the treatment of patients with
      melanoma. This article provides an update on the available evidence on the
      diverse factors (routes of metastatic spread, predictors, adjuvant therapy, etc.)
      that must be considered when treating patients with sentinel node-positive
      melanoma. The authors propose a decision-making algorithm for use in this
      clinical setting. The current evidence no longer supports lymph node dissection
      in patients with low-risk sentinel node metastasis (sentinel node tumor load
      <=1mm).

PMID- 29650222
TI  - Value of Ultrasound as a Diagnostic Tool for a Painful Thoracic Nodule.

PMID- 29650223
TI  - Surgeons' muscle load during robotic-assisted laparoscopy performed with a
      regular office chair and the preferred of two ergonomic chairs: A pilot study.
AB  - Surgeons work in awkward work postures and have high precision demands - well
      known risk factors for musculoskeletal pain. Robotic-assisted laparoscopy is
      expected to be less demanding compared to conventional laparoscopy; however,
      studies indicate that robotic-assisted laparoscopy is also associated with poor
      ergonomics and musculoskeletal pain. The ergonomic condition in the robotic
      console is partially dependent upon the chair provided, which often is a regular
      office chair. Our study quantified and compared the muscular load during robotic
      assisted laparoscopy using one of two custom built ergonomic chairs and a regular
      office chair. The results demonstrated no differences that could be considered
      clinically relevant. Overall, the study showed high levels of static and mean
      muscular activity, increased perceived physical exertion from pre-to-post
      surgery, and moderate to high risk for musculoskeletal injuries measured by the
      Rapid Upper Limb Assessment worksheet. Authors advocate for further investigation
      in surgeons' ergonomics and physical work demands in robotic surgery.

PMID- 29650224
TI  - Examining vehicle operating speeds on rural two-lane curves using naturalistic
      driving data.
AB  - Horizontal curves have been shown to exhibit crash rates significantly higher
      than comparable tangent segments. Extensive research has investigated the causes
      of crashes on horizontal curves, particularly the curve navigation process and
      driver speed selection. Research in this area has generally been limited by the
      nature of the data, which is often inhibited by practical constraints as to the
      number of locations and drivers that can be observed. This study overcomes these
      hurdles through the use of naturalistic driving data, providing insights on how
      drivers navigate and react to curves on rural two-lane highways. Nearly 10,000
      vehicle traces were collected from 202 drivers on 219 horizontal curves as a part
      of this study. All driving traces were collected on rural two-lane highways with
      prevailing posted speed limits of 45 mph or 55 mph, as well as a diverse range of
      curve advisory speeds. Regression models are estimated via generalized estimating
      equations to discern those factors affecting mean speeds on curves. A log-linear
      relationship was found between curve radius and mean vehicle speed, with speeds
      relatively stable on radii of 900-1000 ft. or more, decreasing more rapidly as
      radii decreased below this range. Drivers were found to reduce speeds when curve
      advisories were present, but the magnitude of these reductions was much less than
      suggested by the advisory signs. Speeds were significantly lower when a W1-6
      curve arrow sign was present adjusting for the curve radius. There were also some
      differences in speeds based on driver age and gender. Ultimately, this paper
      provides insights into driver curve navigation and demonstrates the potential of
      high-fidelity naturalistic driving data to assess speed management and geometric
      design on horizontal curves.

PMID- 29650225
TI  - An update on Cushing syndrome in pediatrics.
AB  - Cushing syndrome (CS) in childhood results mostly from the exogenous
      administration of glucocorticoids; endogenous CS is a rare disease. The latter is
      the main reason pediatric patients with CS escape diagnosis for too long. Other
      barriers to optimal care of a pediatric patient with CS include improper
      following of the proper sequence of testing for diagnosing CS, which stems from
      lack of understanding of pathophysiology of the hypothalamic-pituitary-adrenal
      axis; lack of access to proper (i.e., experienced, state-of-the-art) surgical
      treatment; and unavailability of well-tolerated and effective medications to
      control hypercortisolemia. This report reviews the state-of-the-art in diagnosing
      CS and provides an update on the most recent discoveries in its genetics and
      treatment.

PMID- 29650226
TI  - Are Cushing's disease patients curable?
AB  - Treatment of Cushing's disease remains a challenge. Whereas pituitary surgery can
      "cure" the patient and restore a completely normal pituitary adrenal axis, there
      are immediate failures and late recurrences which ultimately require alternate
      therapeutic approaches. These are numerous, but so are their drawbacks, and all
      appear to be "default options". For the future, pituitary adenoma has to remain
      the "reasonable obsession" of efficient and optimistic therapists....

PMID- 29650227
TI  - Reply.

PMID- 29650228
TI  - Visualization of Proliferative Vascular Endothelial Cells in Tumors in Vivo by
      Imaging Their Partner of Sld5-1 Promoter Activity.
AB  - Vascular endothelial cells (ECs) isolated from tumors characteristically express
      certain genes. It has recently been suggested that tumor vessel normalization
      facilitates effective drug delivery into tumors; however, how tumor vessel
      normalization can be recognized on the basis of the molecules expressed by tumor
      ECs is not clearly defined. The degree of cell proliferation is an important
      indicator to characterize the condition of the ECs. Herein, we generated
      transgenic mice expressing enhanced green fluorescent protein (EGFP) under the
      transcriptional control of the DNA replication factor partner of Sld5-1 (PSF1;
      official name GINS1) promoter to assess whether active ECs can be distinguished
      from dormant ECs. Predictably, ECs in the adult skin exhibited no EGFP signals.
      However, after s.c. injection of tumor cells, some ECs shifted to EGFP
      positivity, enabling distinction of EGFP-positive from EGFP-negative cells. We
      found that only a fraction of the EGFP-negative ECs strongly expressed the
      glycosylphosphatidylinositol-anchor protein CD109 associated with the
      phosphatidylinositol 3-kinase pathway. Taken together, these data indicate that
      areas of vascular normalization in tumors can be detected by CD109 expression,
      and this provides a window of opportunity for timing chemotherapy.

PMID- 29650229
TI  - Allergen component analysis as a tool in the diagnosis and management of
      occupational allergy.
AB  - We are now in the epoch of "molecular allergology" and numerous clinically
      relevant allergenic molecules are available improving the performance of in vitro
      allergen tests and allergen detection methods. This review is focusing on
      characterized occupational allergens and their implementation into the in vitro
      diagnosis for occupational allergy and in allergen detection methods. More than
      400 occupational agents are identified and documented as being 'respiratory
      sensitizers', but currently only a limited number of them are characterized on
      the molecular level and available for routine diagnosis as native or recombinant
      allergens. One exception, however, is natural rubber latex (NRL) from Hevea
      brasiliensis still remaining an important occupational allergen source.
      Characterization of 15 NRL allergens led to the development of assays for the
      determination of allergen content of NRL materials and the implementation of
      component-resolved diagnosis (CRD) for specific IgE antibody measurement.
      Microarray or singleplex using recombinant or native allergens are reliable tools
      for NRL allergy diagnosis. In addition, NRL allergy is an excellent model for
      improving extract-based specific IgE measurement by amplification of NRL extract
      preparation with stable recombinant major allergen rHev b 5. Despite the many
      efforts to characterize the occupationally relevant wheat allergens for baker's
      asthma, the most frequently occurring forms of occupational asthma, the results
      are highly diverse. Wheat sensitization profiles of bakers showed great
      interindividual variability and no wheat allergen could be classified as the
      major allergen. For diagnosis of baker's asthma, a whole wheat extract is still
      the best option for specific IgE determination. But single wheat allergens might
      help to discriminate between wheat-induced food allergy, grass pollen allergy and
      baker's asthma. For workplace-related allergens like coffee, wood, soybean,
      seafood and moulds allergens are characterized and few of them are available, but
      their relevance for occupational sensitization routes should be verified in the
      further studies.

PMID- 29650230
TI  - Production of spliced peptides by the proteasome.
AB  - CD8+ cytolytic T lymphocytes are essential players of anti-tumor immune
      responses. On tumors, they recognize peptides of about 8-to-10 amino acids that
      generally result from the degradation of cellular proteins by the proteasome.
      Until a decade ago, these peptides were thought to solely correspond to linear
      fragments of proteins that were liberated after the hydrolysis of the peptide
      bonds located at their extremities. However, several examples of peptides
      containing two fragments originally distant in the protein sequence challenged
      this concept and demonstrated that proteasome could also splice peptides together
      by creating a new peptide bond between two distant fragments. Unexpectedly,
      peptide splicing emerges as an essential way to increase the peptide repertoire
      diversity as these spliced peptides were shown to represent up to 25% of the
      peptides presented on a cell by MHC class I. Here, we review the different steps
      that led to the discovery of peptide splicing by the proteasome as well as the
      lightening offered by the recent progresses of mass spectrometry and
      bioinformatics in the analysis of the spliced peptide repertoire.

PMID- 29650231
TI  - Corrigendum to "37Cl/35Cl isotope ratio analysis in perchlorate by ion
      chromatography/multi collector-ICPMS: Analytical performance and implication for
      biodegradation studies" [Chemosphere 184 (2017) 192-196].

PMID- 29650232
TI  - Antibiotic risk assessment needs to protect both environmental and human health.

PMID- 29650233
TI  - Association between bisphenol a exposure and idiopathic central precocious
      puberty (ICPP) among school-aged girls in Shanghai, China.
AB  - BACKGROUND: Bisphenol A (BPA) is a well-known and widely used endocrine
      disrupter, but data on its association with childhood reproductive development
      are limited. OBJECTIVES: We investigated the possible relationship between
      exposure to BPA and idiopathic central precocious puberty (ICPP) in school-aged
      girls. METHODS: We conducted a 1:1 matched case-control study in Shanghai, China,
      between July 2011 and September 2012. This study included 136 school-aged (6 to 9
      years old) girls diagnosed with ICPP and 136 controls matched for age and body
      mass index (BMI). We measured the urinary BPA concentrations of all the girls and
      examined the association with odds of having ICPP. Laboratory examinations
      including serum estradiol (E2) levels, basal and gonadotropin-releasing hormone
      (GnRH)-stimulated luteinizing hormone (LH), and follicle-stimulating hormone
      (FSH) levels, bone ages (BA), and uterine and ovarian sizes were conducted in the
      ICPP girls. RESULTS: Median concentrations of urinary BPA in the ICPP and control
      groups were 6.35 and 1.17 MUg/g creatinine (Cr), respectively (p < 0.001). After
      adjustment for confounders, compared to those with the lowest concentrations of
      BPA, the highest concentrations were associated with a 9.08-fold increased odds
      of having ICPP [odds ratio (OR) = 9.08, (95% confidence interval (CI): 2.83
      29.15)]. In the ICPP group, modest negative correlation was present between
      urinary BPA concentrations (MUg/g Cr) and peak FSH levels [beta = -0.090 (95% CI:
      -0.178, -0.003), p = 0.044]. CONCLUSIONS: Our findings suggest that BPA exposure
      is associated with increased odds of having ICPP in school-aged girls, and the
      potential mechanism may be attributable to the relatively low FSH levels.

PMID- 29650234
TI  - Re: Refined Analysis of Prostate-specific Antigen Kinetics to Predict Prostate
      Cancer Active Surveillance Outcomes.

PMID- 29650235
TI  - Re: Adjuvant Sandwich Chemotherapy Plus Radiotherapy vs Adjuvant Chemotherapy
      Alone for Locally Advanced Bladder Cancer After Radical Cystectomy: A Randomized
      Phase 2 Trial.

PMID- 29650236
TI  - Re: WATER: A Double-blind, Randomized, Controlled Trial of Aquablation vs
      Transurethral Resection of the Prostate in Benign Prostatic Hyperplasia.

PMID- 29650237
TI  - Relation Between Wrist Circumference and Left Ventricular Structure in Overweight
      Children.
AB  - The aim of this study was to assess the relation of wrist circumference with
      changes in left ventricular (LV) structure in a population of overweight/obese
      children and adolescents. One hundred and six children and adolescents were
      consecutively enrolled. In all subjects body weight, height, wrist circumference,
      waist circumference, body mass index-standard deviation score, fasting glucose,
      insulin, lipid profile, and blood pressure were evaluated. All subjects underwent
      echocardiographic assessment, and the following parameters were evaluated: LV
      dimension at end diastole and LV dimension at end systole, LV posterior wall
      thickness at end diastole and LV posterior wall thickness at end systole,
      interventricular septal thickness at end diastole and interventricular septal
      thickness at end systole, LV mass, and epicardial adipose tissue (EAT). LV
      hypertrophy was defined as LVM Index >=95th percentile. Wrist circumference
      correlated with all parameters of LV dimensions and LV mass (p <0.0001) and EAT
      (p = 0.04). The strongest correlations were reported between wrist circumference
      with LV dimension at end diastole and LV dimension at end systole (r = 0.73 and r
      = 0.68 respectively, p <0.0001, for both). Results of the multivariate regression
      analysis showed that wrist circumference was significantly associated with all
      parameters of LV dimensions, LV mass, and EAT (p <=0.002). The logistic
      regression showed that wrist circumference was significantly associated with LV
      hypertrophy (odds ratio 1.39, p = 0.046). In conclusion, wrist circumference
      could be a useful measure of cardiovascular risk in obese children and
      adolescents, opening new perspectives in the prediction of cardiovascular
      diseases.

PMID- 29650238
TI  - Incidence, Timing, Causes and Predictors of Early and Late Re-Hospitalization in
      Patients Who Underwent Percutaneous Mitral Valve Repair With the MitraClip
      System.
AB  - The pattern and reasons for re-hospitalization (RH) after MitraClip implantation
      are not well characterized. A total of 322 consecutive MitraClip patients were
      included, with data stratified by RH status. Multivariate analyses were conducted
      to identify predictors of early (30-day) and late (30-day to 12-month) RH. Eighty
      nine patients (27.6%) were readmitted to hospital during the study period and
      early RH occurred in 27%. The median time from MitraClip to RH was 99 days. RH
      was mostly related to cardiovascular causes (66.3%). Anemia and gastrointestinal
      bleeding were the most frequent noncardiovascular causes. Independent predictors
      of early RH were length of stay >=3 days during the index procedure (odds ratio
      [OR] 4.13, 95% confidence interval [CI] 1.32 to 12.91), reduction of left
      ventricular ejection fraction >=5% after MitraClip implantation (OR 4.88, 95% CI
      1.36 to 18.91), and severe systolic pulmonary artery pressure >=60 mm Hg at
      discharge (OR 3.72, 95% CI 1.23 to 11.26). Conversely, the independent predictors
      of late RH were device failure (OR 4.02, 95% CI 1.22 to 13.25) and systolic
      pulmonary artery pressure >=60 mm Hg at discharge (OR 2.34, 95% CI 1.01 to 5.44).
      In patients with early RHs, survival was significantly worse at 12 months
      compared with patients with late RH and no-RH (69.3% vs 82.6% vs 86%, p <0.001).
      In conclusion, RH is not uncommon after MitraClip implantation and cardiovascular
      causes represent its most frequent etiology. Clinical and echocardiographic
      predictors of early and late RH can be identified at discharge. Early RH carries
      a worse prognosis than late RH.

PMID- 29650239
TI  - Lifestyle Therapy for the Management of Atrial Fibrillation.
AB  - Atrial fibrillation (AF) is a common arrhythmia associated with increased risk of
      morbidity and mortality. There is evidence that lifestyle interventions may serve
      as complementary treatments to reduce AF burden. The objective of this review was
      to summarize the efficacy of lifestyle interventions for the management of AF.
      Studies which included patients with systolic heart failure (ejection fraction
      <=40%), and those limited to an examination of vigorous physical activity were
      excluded from our search. Studies were identified through a search of the
      following databases: MEDLINE, EMBASE, CINAHIL, and PubMed, run from inception
      through August 2016. All studies were graded for quality using the Oxford Centre
      for Evidence-based Medicine recommendations. Meta-analyses of the studies were
      not performed due to the heterogeneity of the studies. From a total of 1,811
      publications, 10 articles were identified and included. Selected publications
      included 1 study on yoga, 2 studies on acupuncture, 3 studies that examined
      weight loss programs, and 4 studies that evaluated the impact of moderate
      physical activity. Yoga was associated with less symptomatic AF episodes and
      improved quality of life. Acupuncture was associated with reduced AF occurrence
      in patients with persistent and paroxysmal AF. Weight loss was associated with a
      significant reduction AF burden and symptoms. Moderate exercise resulted in
      greater arrhythmia free survival and a mean reduction in AF burden. In
      conclusion, evidence exists to suggest that yoga, weight loss, and moderate
      exercise are associated with reductions in AF burden and symptoms. Evidence is
      greatest for weight loss and moderate exercise.

PMID- 29650240
TI  - Serum Bisphenol A is an independent risk factor of hyperuricemia: A 6-year
      prospective study.
AB  - OBJECTIVE: This study aims to evaluate whether serum Bisphenol A (BPA) is a risk
      factor for hyperuricemia. METHODS: In this prospective study, a total of 482
      participants without hyperuricemia were enrolled at baseline and followed up for
      6 years. Clinical characteristics were recorded, and serum levels of uric acid
      and BPA were measured. Participants were stratified into tertiles according to
      low, median, and high baseline serum BPA levels. Regression models were used to
      analyze associations of serum BPA with the change in uric acid and the risk of
      developing hyperuricemia. RESULTS: At baseline, serum concentrations of BPA was
      0.51 (0.24-2.37) ng/mL. After 6 years of follow-up, the change in serum uric acid
      concentration from baseline to the 6-year mark was significantly higher in
      subjects with higher baseline BPA concentration (0.03 +/- 0.19, 0.07 +/- 0.21,
      and 0.11 +/- 0.25mg/dL for low, median, and high tertiles, respectively, P =
      0.006). When adjusted for potential confounders, such as age, renal function, and
      history of diabetes and hypertension, multivariable logistic analyses showed that
      subjects in the median or high baseline BPA tertiles exhibited a twofold higher
      risk of 6-year hyperuricemia incidence compared to subjects in the low baseline
      BPA tertile [odds ratio (OR) = 2.28 (95% CI: 1.05-4.95) for the median tertile;
      2.42 (1.07-5.48) for the high tertile, Pfor Trend = 0.043]. CONCLUSION: In
      conclusion, serum BPA is an independent risk factor for hyperuricemia.

PMID- 29650241
TI  - Input-to-state stability of time-varying nonlinear discrete-time systems via
      indefinite difference Lyapunov functions.
AB  - In this paper, we propose new sufficient criteria for input-to-state stability
      (ISS) of time-varying nonlinear discrete-time systems via indefinite difference
      Lyapunov functions. The proposed sufficient conditions for ISS of system are more
      relaxed than for ISS with respect to Lyapunov functions with negative definite
      difference. We prove system is ISS by two methods. The first way is to prove
      system is ISS by indefinite difference ISS Lyapunov functions. The second method
      is to prove system is ISS via introducing an auxiliary system and indefinite
      difference robust Lyapunov functions. The comparison of the sufficient conditions
      for ISS obtained via the two methods is discussed. The effectiveness of our
      results is illustrated by three numerical examples.

PMID- 29650242
TI  - Pain after ortho-plastic reconstruction of lower limb injuries: The importance of
      standardizing analgesic management.

PMID- 29650243
TI  - Testicular macrophages: Guardians of fertility.
AB  - Macrophages are innate immune cells present in essentially every organ of the
      body with dedicated tissue specific functions. We will present in this review the
      unique properties and functions of macrophage populations residing in the testis,
      an immune-privileged organ. Testicular macrophages (tMPhi) could be seen as
      guardians of fertility due to their immunosuppressive functions protecting
      spermatogenesis from auto immune-attack. They exhibit testis specific functions
      with essential roles in normal testis homeostasis and fetal testicular
      development. Recently, two distinct testicular macrophage populations have been
      characterized based on different localization, morphology, gene expression
      profiles, developmental origin and postnatal development. We will discuss the
      importance of these two testicular macrophage populations for organ specific
      functions such as testosterone production and spermatogenesis, as well as their
      role in establishing immuno-privilege highlighting the contributions of
      macrophages to male fertility.

PMID- 29650244
TI  - Heart macrophages and dendritic cells in sickness and in health: A tale of a
      complicated marriage.
AB  - Heart disease is the major cause of death and it is broadly recognized that the
      immune system plays a central role in healthy and injured heart. Here, we focus
      on the contribution of various subsets of mononuclear phagocytes in the cardiac
      system. Macrophages and dendritic cells reside in the healthy myocardium to
      fulfill homeostatic functions and rapidly increase in numbers in diseases like
      myocardial ischemia and myocarditis to contribute to disease or resolve it.
      Recent experiments have revealed the extraordinary heterogeneity of cardiac
      mononuclear phagocytes that differ in origin, lifespan, phenotype and function.
      Although many studies described cardiac phagocytes in the mouse, subsets of
      cardiac mononuclear phagocytes can also be broadly found in the human heart,
      opening up the potential of selective targeting of these cells in a therapeutic
      setting. Before this goal can be achieved we need better understanding not only
      of the detrimental but also beneficial functions of these highly diverse cells in
      the heart.

PMID- 29650245
TI  - Integrated care in Switzerland: Results from the first nationwide survey.
AB  - INTRODUCTION: Due to fragmentation of care delivery, health systems are under
      pressure and integrated care is advocated for. Compared to the numerous existing
      integrated care initiatives in Europe and elsewhere, Switzerland seems to lag
      behind. METHODS: The objective of the survey was to produce a comprehensive
      overview of integrated care initiatives in Switzerland. To be included,
      initiatives needed to meet four criteria: present some type of formalization,
      consider >2 different groups of healthcare professionals, integrate >2 healthcare
      levels, be ongoing. We systematically contacted major health system organizations
      at federal, cantonal and local level. Between 2015 and 2016, we identified 172
      integrated care initiatives and sent them a questionnaire. We performed
      descriptive analyses. RESULTS: Integrated care initiatives in Switzerland are
      frequent and increasing. The implementation of initiatives over time, their
      distribution between linguistic areas, the number of healthcare levels
      integrated, and the number of professionals involved vary according to the type
      of initiatives. DISCUSSION: Despite Switzerland's federalist structure and
      organization of healthcare, and only recent incentives to develop integrated
      care, initiatives are frequent and diverse. Stakeholders should support existing
      initiatives and facilitate their development. They should also promote innovative
      avenues, experiment alternative payment models for integrated care, foster people
      centeredness and incentivize interprofessional models. This will require systems
      thinking and contributions from all actors of the healthcare system.

PMID- 29650246
TI  - Public Health Science Conference: a call for abstracts.

PMID- 29650247
TI  - Department of Error.

PMID- 29650249
TI  - The emerging Chinese COPD epidemic.

PMID- 29650248
TI  - Prevalence and risk factors of chronic obstructive pulmonary disease in China
      (the China Pulmonary Health [CPH] study): a national cross-sectional study.
AB  - BACKGROUND: Although exposure to cigarette smoking and air pollution is common,
      the current prevalence of chronic obstructive pulmonary disease (COPD) is unknown
      in the Chinese adult population. We conducted the China Pulmonary Health (CPH)
      study to assess the prevalence and risk factors of COPD in China. METHODS: The
      CPH study is a cross-sectional study in a nationally representative sample of
      adults aged 20 years or older from ten provinces, autonomous regions, and
      municipalities in mainland China. All participants underwent a post
      bronchodilator pulmonary function test. COPD was diagnosed according to 2017
      Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria. FINDINGS:
      Between June, 2012, and May, 2015, 57 779 individuals were invited to
      participate, of whom 50 991 (21 446 men and 29 545 women) had reliable post
      bronchodilator results and were included in the final analysis. The overall
      prevalence of spirometry-defined COPD was 8.6% (95% CI 7.5-9.9), accounting for
      99.9 (95% CI 76.3-135.7) million people with COPD in China. Prevalence was higher
      in men (11.9%, 95% CI 10.2-13.8) than in women (5.4%, 4.6-6.2; p<0.0001 for sex
      difference) and in people aged 40 years or older (13.7%, 12.1-15.5) than in those
      aged 20-39 years (2.1%, 1.4-3.2; p<0.0001 for age difference). Only 12.0% (95% CI
      8.1-17.4) of people with COPD reported a previous pulmonary function test. Risk
      factors for COPD included smoking exposure of 20 pack-years or more (odds ratio
      [OR] 1.95, 95% CI 1.53-2.47), exposure to annual mean particulate matter with a
      diameter less than 2.5 MUm of 50-74 MUg/m3 (1.85, 1.23-2.77) or 75 MUg/m3 or
      higher (2.00, 1.36-2.92), underweight (body-mass index <18.5 kg/m2; 1.43, 1.03
      1.97), sometimes childhood chronic cough (1.48, 1.14-1.93) or frequent cough
      (2.57, 2.01-3.29), and parental history of respiratory diseases (1.40, 1.23
      1.60). A lower risk of COPD was associated with middle or high school education
      (OR 0.76, 95% CI 0.64-0.90) and college or higher education (0.47, 0.33-0.66).
      INTERPRETATION: Spirometry-defined COPD is highly prevalent in the Chinese adult
      population. Cigarette smoking, ambient air pollution, underweight, childhood
      chronic cough, parental history of respiratory diseases, and low education are
      major risk factors for COPD. Prevention and early detection of COPD using
      spirometry should be a public health priority in China to reduce COPD-related
      morbidity and mortality. FUNDING: Ministry of Health and Ministry of Science and
      Technology of China.

PMID- 29650250
TI  - Thermo-setting glass ionomer cements promote variable biological responses of
      human dental pulp stem cells.
AB  - OBJECTIVE: To evaluate the in vitro cytotoxicity of Equia Forte (GC, Tokyo,
      Japan) and Ionostar Molar (Voco, Cuxhaven, Germany) on human dental pulp stem
      cells (hDPSCs). METHODS: hDPSCs isolated from third molars were exposed to
      several dilutions of Equia Forte and Ionostar Molar eluates (1/1, 1/2 and 1/4).
      These eluates were obtained by storing material samples in respective cell
      culture medium for 24h (n=40). hDPSCs in basal growth culture medium were the
      control. Cell viability and cell migration assays were performed using the MTT
      and wound-healing assays, respectively. Also, induction of apoptosis and changes
      in cell phenotype were evaluated by flow cytometry. Changes in cell morphology
      were analysed by immunocytofluorescence staining. To evaluate cell attachment to
      the different materials, hDPSCs were directly seeded onto the material surfaces
      and analyzed by scanning electron microscopy (SEM). The chemical composition of
      the materials was determined by energy dispersive X-ray (EDX) and eluates were
      analyzed by inductively coupled plasma-mass spectrometry (ICP-MS). Statistical
      analysis was performed with analysis of variance (ANOVA) and Student's t-test
      (alpha<0.05). RESULTS: Undiluted Equia Forte extracts led to a similar cell
      proliferation rates than the control group from 72h onwards. There were no
      significance differences between Equia Forte and Ionostar Molar in terms of cell
      apoptosis and phenotype. However, in presence of Equia extracts the migration
      capacity of hDPSCs was higher than in presence of Ionostar Molar (p<0.05). Also,
      SEM studies showed a higher degree of cell attachment when Equia Forte extracts
      were used. Finally, EDX analysis pointed to different weight percentages of C, O
      and Ca ions in glass ionomer cements, while other elements such as La, Al, Si, W,
      Mo and F were also detected. SIGNIFICANCE: In summary, Equia Forte promoted
      better biological responses in hDPSCs than Ionostar Molar.

PMID- 29650251
TI  - Exploring the molecular mechanisms of Traditional Chinese Medicine components
      using gene expression signatures and connectivity map.
AB  - BACKGROUND AND OBJECTIVE: Traditional Chinese Medicine (TCM) has been practiced
      over thousands of years in China and other Asian countries for treating various
      symptoms and diseases. However, the underlying molecular mechanisms of TCM are
      poorly understood, partly due to the "multi-component, multi-target" nature of
      TCM. To uncover the molecular mechanisms of TCM, we perform comprehensive gene
      expression analysis using connectivity map. METHODS: We interrogated gene
      expression signatures obtained 102 TCM components using the next generation
      Connectivity Map (CMap) resource. We performed systematic data mining and
      analysis on the mechanism of action (MoA) of these TCM components based on the
      CMap results. RESULTS: We clustered the 102 TCM components into four groups based
      on their MoAs using next generation CMap resource. We performed gene set
      enrichment analysis on these components to provide additional supports for
      explaining these molecular mechanisms. We also provided literature evidence to
      validate the MoAs identified through this bioinformatics analysis. Finally, we
      developed the Traditional Chinese Medicine Drug Repurposing Hub (TCM Hub) - a
      connectivity map resource to facilitate the elucidation of TCM MoA for drug
      repurposing research. TCMHub is freely available in
      http://tanlab.ucdenver.edu/TCMHub. CONCLUSIONS: Molecular mechanisms of TCM could
      be uncovered by using gene expression signatures and connectivity map. Through
      this analysis, we identified many of the TCM components possess diverse MoAs,
      this may explain the applications of TCM in treating various symptoms and
      diseases.

PMID- 29650252
TI  - The interferon-stimulated gene TRIM22: A double-edged sword in HIV-1 infection.
AB  - Infection of target cells by the human immunodeficiency virus type-1 (HIV-1) is
      hampered by constitutively expressed host cell proteins preventing or curtailing
      virus replication and therefore defined as "restriction factors". Among them,
      members of the tripartite motif (TRIM) family have emerged as important players
      endowed with both antiviral effects and modulatory capacity of the innate immune
      response. TRIM5alpha and TRIM19 (i.e. promyelocytic leukemia, PML) are among the
      best-characterized family members; however, in this review we will focus on the
      potential role of another family member, i.e. TRIM22, a factor strongly induced
      by interferon stimulation, in HIV infection in vivo and in vitro in the context
      of its broader antiviral effects. We will also focus on the potential role of
      TRIM22 in HIV-1-infected individuals speculating on its dual role in controlling
      virus replication and more complex role in chronic infection. At the molecular
      levels, we will review the evidence in favor of a relevant role of TRIM22 as
      epigenetic inhibitor of HIV-1 transcription acting by preventing the binding of
      the host cell transcription factor Sp1 to the viral promoter. These evidences
      suggest that TRIM22 should be considered a potential new player in either the
      establishment or maintenance of HIV-1 reservoirs of latently infected cells
      unaffected by combination antiretroviral therapy.

PMID- 29650253
TI  - Small Cell Breast Cancer with Lung Metastases.

PMID- 29650254
TI  - NUT Midline Carcinoma in the Mediastinum in a Ten-Year-Old Boy.

PMID- 29650255
TI  - Glucocorticoid-loaded liposomes induce a pro-resolution phenotype in human
      primary macrophages to support chronic wound healing.
AB  - Glucocorticoids are well established anti-inflammatory agents, however, their use
      to treat chronic inflammatory diseases is limited due to a number of serious side
      effects. For example, long-term local treatment of chronic wounds with
      glucocorticoids is prohibited by dysregulation of keratinocyte and fibroblast
      function, leading to skin thinning. Here, we developed and tested liposome
      formulations for local delivery of dexamethasone to primary human macrophages, to
      drive an anti-inflammatory/pro-resolution phenotype appropriate for tissue
      repair. The liposomes were loaded with the pro-drug dexamethasone-phosphate and
      surface-modified with either polyethylene glycol or phosphatidylserine. The
      latter was used to mimic phosphatidylserine-harboring apoptotic cells, which are
      substrates for efferocytosis, an essential pro-resolution function. Both
      formulations induced a dexamethasone-like gene expression signature in
      macrophages, decreased IL6 and TNFalpha release, increased secretion of
      thrombospondin 1 and increased efferocytosis activity. Phosphatidylserine
      modified liposomes exhibited a faster uptake, a higher potency and a more robust
      phenotype induction than polyethylene glycol-modified liposomes. Fibroblast and
      keratinocyte cell cultures as well as a 3D skin equivalent model showed that
      liposomes applied locally to wounds are preferentially phagocytosed by
      macrophages. These findings indicate that liposomes, in particular upon shell
      modification with phosphatidylserine, promote dexamethasone delivery to
      macrophages and induce a phenotype suitable to support chronic wound healing.

PMID- 29650256
TI  - Impact of route and adequacy of nutritional intake on outcomes of allogeneic
      haematopoietic cell transplantation for haematologic malignancies.
AB  - BACKGROUND: Allogeneic haematopoietic cell transplantation (HCT) is often
      associated with poor oral intake due to painful mucositis and gastrointestinal
      sequalae that occur following a preparative regimen of intensive chemotherapy
      and/or total body radiation. Although attractive to assume that optimal nutrition
      improves HCT outcomes, there are limited data to support this. It is also unclear
      whether artificial nutrition support should be provided as enteral tube feeding
      or parenteral nutrition (PN). METHODS: We analysed day-100 non-relapse mortality
      (NRM), incidence of acute graft-versus-host disease (GvHD), acute
      gastrointestinal GvHD, 5-year survival and GvHD-free/relapse-free survival (GRFS)
      according to both route and adequacy of nutritional intake prior to neutrophil
      engraftment, together with other known prognostic factors, in a retrospective
      cohort of 484 patients who underwent allogeneic HCT for haematologic malignancy
      between 2000 and 2014. RESULTS: Multivariate analyses showed increased NRM with
      inadequate nutrition (hazard ratio (HR) 4.1; 95% confidence interval (CI) 2.2
      7.2) and adequate PN (HR 2.9; 95% CI 1.6-5.4) compared to adequate enteral
      nutrition (EN) both P < .001. There were increased incidences of gastrointestinal
      GvHD of any stage and all GvHD >= grade 2 in patients who received PN (odds ratio
      (OR) 2.0; 95% CI 1.2-3.3; P = .006, and OR 1.8; 95% CI 1.1-3.0; P = .018,
      respectively), compared to adequate EN. Patients who received adequate PN and
      inadequate nutrition also had reduced probabilities of survival and GRFS at 5
      years. CONCLUSION: Adequate EN during the early transplantation course is
      associated with reduced NRM, improved survival and GRFS at 5 years. Furthermore,
      adequate EN is associated with lower incidence of overall and gut acute GvHD than
      PN, perhaps because of its ability to maintain mucosal integrity, modulate the
      immune response to intensive chemo/radiotherapy and support the gastrointestinal
      tract environment, including gut microflora.

PMID- 29650258
TI  - [Chorioretinal anastomosis as a complication of idiopathic macular telangiectasia
      type 2].

PMID- 29650257
TI  - Neuropeptide Y mitigates ER stress-induced neuronal cell death by activating the
      PI3K-XBP1 pathway.
AB  - The unfolded protein response (UPR) is an evolutionarily conserved adaptive
      reaction that increases cell survival under endoplasmic reticulum (ER) stress
      conditions. ER stress-associated neuronal cell death pathways play roles in the
      pathogenesis of neurodegenerative diseases, including Alzheimer's, Parkinson's,
      and Huntington's disease. Neuropeptide Y (NPY) has an important role in
      neuroprotection against neurodegenerative diseases. In this study, we
      investigated whether NPY has a protective role in ER stress-induced neuronal cell
      death in SK-N-SH human neuroblastoma cells. An ER stress-inducing chemical,
      tunicamycin, increased the activities of caspase-3 and -4, whereas pretreatment
      with NPY decreased caspase-3 and -4 activities during the ER stress response. In
      addition, NPY suppressed the activation of three major ER stress sensors during
      the tunicamycin-induced ER stress response. NPY-mediated activation of PI3K
      increased nuclear translocation of XBP1s, which in turn induced expression of
      Grp78/BiP. Taken together, our data indicated that NPY plays a protective role in
      ER stress-induced neuronal cell death through activation of the PI3K-XBP1
      pathway, and that NPY signaling can serve as therapeutic target for ER stress
      mediated neurodegenerative diseases.

PMID- 29650259
TI  - Intralenticular Ozurdex implant: What to do and how.

PMID- 29650260
TI  - [Bilateral "Mickey Mouse" posterior synechiae].

PMID- 29650261
TI  - Maribavir, brincidofovir and letermovir: Efficacy and safety of new antiviral
      drugs for treating cytomegalovirus infections.
AB  - Cytomegalovirus (CMV) infection is a common complication in immunocompromised
      patients, especially after hematopoietic stem cell or solid organ
      transplantation. Therapeutic antiviral options [(val)ganciclovir, foscarnet,
      cidofovir] are still limited and can expose to severe toxicities. Moreover,
      prolonged antiviral drug exposure and ongoing viral replication are key factors
      in the development of antiviral drug resistance. After many years of few tangible
      advances in terms of new antiviral drugs, we are now experiencing an exciting
      period characterized by a series of phase III clinical trials incorporating three
      novel agents: maribavir, brincidofovir, and letermovir. This article summarizes
      the current state of the prevention and treatment of CMV infections as well as
      data of investigational drugs in clinical development.

PMID- 29650262
TI  - Triple flap technique for vulvar reconstruction.
AB  - OBJECTIVE: Perineal defects are encountered ever more frequently, in the
      treatment of vulvar cancers or abdominoperineal resection. The surgical treatment
      of vulvar cancer leads to significant skin defect. The aim of the reconstruction
      is not to provide volume but rather to resurface perineum. We propose a new
      solution to cover the extensive skin defect remaining after excision. METHODS: We
      report 3 patients who underwent large excision for vulvar cancer, with lymph node
      dissection. For reconstruction, we performed 3 advancement flaps. Two V-Y flaps
      cantered on the infra-gluteal folds and based on pudendal perforator arteries
      were used to cover the postero-lateral parts of the defect. The third advancement
      flap from the superior aspect of the defect was a Y-V Mons pubis flap. RESULTS:
      The defects were successfully covered by the 3 flap technique. The first patient
      suffered a non-union that slowly healed by secondary intention. For the other
      cases, we used the same technique, but applied negative pressure wound therapy on
      the sutures, with excellent results. CONCLUSION: The 3 flap technique is a simple
      and reliable method and the donor site morbidity is minimal. It can be realised
      without changing the position of the patient after tumour excision, and does not
      require delicate perforator dissection. This surgical option can be easily
      applied, allowing better management of these cases.

PMID- 29650263
TI  - [Should surgeons keep performing drainage after breast reduction?]
AB  - OBJECTIVE: Despite the absence of "evidence-based medicine", the use of closed
      suction drainage in breast surgery is currently the standard practice. Its goal
      is to minimize the amount of fluid at the operation site, the dead space that can
      involve postoperative complications. The purpose of this study is to demonstrate
      that with or without drainage the complication rate is unchanged. METHODS: We
      conducted a retrospective and comparative study of two groups of breast reduction
      with and without drainage. Every complication has been recorded and statistically
      analyzed: seroma and hematoma, infections, wound breakdown, skin flap or nipple
      areola complex necrosis, fat necrosis and reoperation. RESULTS: A total of 138
      breast reductions were performed (37 drained patients and 32 non-drained). Data
      collection of complications was done on average 10months after the operation (1
      15). There was no statistical difference between the two groups regarding the
      complication rate. Our results confirm the ones found in the literature.
      CONCLUSION: Except for specific cases (e.g. gigantomasty), this study
      demonstrates that after breast reduction, drainage is not appropriate. Drains do
      not reduce postoperative complications and can increase hospitalization length of
      stay (inducing higher costs). Furthermore, it is often source of pain, anxiety
      and discomfort for patients.

PMID- 29650264
TI  - Diagnostic accuracy of bioimpedance spectroscopy in patients with lymphedema: A
      retrospective cohort analysis.
AB  - BACKGROUND: Bioimpedance spectroscopy (BIS) is used by healthcare specialists to
      diagnose lymphedema. BIS measures limb fluid content by assessing tissue
      resistance to the flow of electric current. However, there is debate regarding
      the validity of BIS in diagnosing early lymphedema. Indocyanine green (ICG)
      lymphography has been established as the most accurate diagnostic modality to
      date for lymphedema diagnosis. In this retrospective study, we test the
      sensitivity, specificity, and diagnostic accuracy of BIS in diagnosing lymphedema
      by referencing its results with ICG lymphography. METHODS: Patients presented to
      the University of Iowa Lymphedema Center from 2015 to 2017 were evaluated with a
      standardized protocol that included history and physical examination, a validated
      lymphedema-specific quality-of-life assessment (LYMQOL), circumference 
      measurement-based index, BIS, and ICG lymphography. Diagnostic accuracy of BIS
      was assessed using ICG lymphography as a reference test. RESULTS: Fifty-eight
      patients had positive ICG lymphography results, which confirmed the diagnosis of
      lymphedema. ICG lymphographic findings consistently correlated with clinical
      examination, LYMQOL evaluation, and lymphedema indices. By contrast, BIS
      demonstrated a false-negative rate of 36% - 21 out of 58 patients had normal BIS
      readings, but a positive ICG lymphography result. The 21 false-negative results
      occurred in patients with early-stage disease. Sensitivity and specificity for
      BIS were 0.64 and 1, respectively. CONCLUSION: BIS carries an excessively high
      rate of false-negative results to be dependably used as a diagnostic modality for
      lymphedema. ICG lymphography highly correlates with other tracking modalities,
      and it remains the most reliable tool for diagnosing lymphedema.

PMID- 29650265
TI  - Anaemia in patients who underwent vascular surgery: a significant predictor of
      amputation and death.
AB  - BACKGROUND AND OBJECTIVE: In patients with peripheral artery disease requiring
      surgery, anaemia has been found to independently predict short and medium term
      higher morbidity and mortality. PATIENTS AND METHODS: We retrospectively studied
      all patients undergoing surgery, consecutively during 2months in 12 vascular
      surgery units. We analysed cardiovascular risk factors and preoperative
      haemoglobin. Statistical analysis was done with Kaplan-Meier for survival and
      logistic regression modelling to identify predictors of mortality. RESULTS: 518
      patients were consecutively operated on in our vascular units, the mortality rate
      was 21% the first year and 34% for cardiovascular events. Preoperative anaemia
      was present in 63% of the ischemic patients and in 23% of the patients requiring
      aneurysm repair, one year after surgery it increased to 68% and 50% respectively.
      When preoperative anaemia was superior to 10mg/dl, one year survival increased
      (96% vs. 90%), fewer cardiovascular events occurred and there were fewer
      amputations (24% vs. 68%). CONCLUSIONS: On multivariable analysis: age, renal
      failure, chronic lung disease, coronary artery disease, postoperative
      complications and previous cardiovascular events were associated with an
      increased risk mortality rate. Preoperative haemoglobin influenced proportionally
      such that for every 1mg /dl increase, the probability of mortality decreases by
      0.81. Preoperative anaemia, especially when haemoglobin is inferior to 10mg/dl,
      is associated with an increased risk of death and amputation.

PMID- 29650266
TI  - Increased sensorimotor network connectivity associated with clozapine eligibility
      in people with schizophrenia.
AB  - Schizophrenia is a heterogeneous disorder that exhibits variable responsiveness
      to treatment between individuals. Here we conducted a resting-state functional
      magnetic resonance imaging (rs-fMRI) study to determine whether resistance to
      first-line antipsychotics is reflected in resting-state connectivity. rs-fMRI
      data were collected from 15 people who had failed to respond to first-line
      antipsychotics (clozapine-eligible) and 10 first-line treatment responders (FLR).
      Image pre-processing and analysis were performed using FMRIB's software library
      (FSL). Data was decomposed into spatial and temporal components using independent
      components analysis. Connectivity within each independent component was compared
      between groups using t-tests and the Bonferroni correction for multiple
      comparisons. Gender was added as a covariate. Clozapine-eligible individuals
      exhibited enhanced functional connectivity within the sensorimotor network
      compared with FLR. Those eligible for clozapine showed additional connectivity
      with the precuneus compared with FLR. No other comparisons reached statistical
      significance and no effect of gender was observed. These data reveal differences
      in functional connectivity between FLR and those eligible for clozapine and
      suggest that greater connectivity between the SMN and precuneus may be indicative
      of treatment resistance in people with schizophrenia.

PMID- 29650267
TI  - Virtual Touch Tissue Quantification for Assessing Renal Pathology in Idiopathic
      Nephrotic Syndrome.
AB  - The aim of this study was to evaluate Virtual Touch tissue quantification in
      assessing renal interstitial fibrosis in patients with idiopathic nephrotic
      syndrome. Ninety patients with idiopathic nephrotic syndrome were assigned to
      mild, moderate and severe groups depending on the degree of renal interstitial
      fibrosis on histopathologic examination of renal biopsy specimens. Thirty healthy
      patients were also selected as the control group. Virtual Touch tissue
      quantification was performed to measure the shear wave velocity of the renal
      parenchyma. There was no statistically significant difference in shear wave
      velocity between the mild and control groups (p > 0.05); however, the moderate
      and severe groups did significantly differ compared with the control (p <0.001).
      The area under the receiver operating characteristic curve value for the shear
      wave velocity of renal interstitial fibrosis in the moderate group versus the
      control and mild groups together was 0.869 (95% confidence interval: 0.791-0.947)
      and that in the severe group versus the control, mild and moderate groups
      together was 0.954 (95% confidence interval: 0.917-0.998). The corresponding best
      cutoff points were 2.41 and 2.77 m/s, with sensitivities of 91.7% and 86.8%,
      specificities of 78.0% and 92.0%, negative predictive values 0.907 and 0.907,
      positive predictive values 0.800 and 0.971 and Youden index values of 0.697 and
      0.788, respectively. Virtual Touch tissue quantification may non-invasively and
      quantitatively estimate the degree of renal interstitial fibrosis in patients
      with idiopathic nephrotic syndrome as a baseline for monitoring progression and
      treatment response.

PMID- 29650268
TI  - Efficacy and toxicity profile of carfilzomib based regimens for treatment of
      multiple myeloma: A systematic review.
AB  - Standard induction therapy for multiple myeloma is three-drug combination based
      on following classes of drugs: proteasome inhibitors, immunomodulators and
      steroids. Despite its notable efficacy, bortezomib has side effects like
      peripheral neuropathy (PNP) with reported incidence of grade >=3 PNP between 2%
      23% Schlafer et al., 2017. Carfilzomib (CFZ) has high selectivity and minimal off
      target adverse effects including lower rates of PNP. CFZ is already approved for
      treatment of relapsed and refractory multiple myeloma (RRMM) as single agent as
      well as in combination with lenalidomide and/or dexamethasone. Extensive
      literature search identified a total of 1839 articles. Twenty-six articles (n =
      5980) met the inclusion criteria, 15 in newly diagnosed multiple myeloma (NDMM)
      and 11 in RRMM group. CFZ demonstrates comparable or even better efficacy to
      bortezomib with much favorable AE profile. Deep, rapid and sustainable response
      using KRd with safer toxicity profile supports extension of KRd therapy to
      frontline therapy for all risk categories of MM. High incidence of grade >=3 HTN
      underscores the importance of serial BP monitoring. In RRMM, CFZ has documented
      efficacy with standard 20-27mg/m2 dose. Further large-scale trials are needed to
      study benefit-to-risk profile of 20-56 and 20-70 mg/m2 dose of CFZ vs standard 20
      27 mg/m2 dose in NDMM and RRMM.

PMID- 29650269
TI  - Current perspectives on the crosstalk between lung cancer stem cells and cancer
      associated fibroblasts.
AB  - Lung cancer, in particular non-small cell lung carcinoma (NSCLC), is the second
      most common cancer in both men and women and the leading cause of cancer-related
      deaths worldwide. Its prognosis and diagnosis are determined by several driver
      mutations and diverse risk factors (e.g. smoking). While immunotherapy has proven
      effective in some patients, treatment of NSCLC using conventional chemotherapy is
      largely ineffective. The latter is believed to be due to the existence of a
      subpopulation of stem-like, highly tumorigenic and chemoresistant cells within
      the tumor population known as cancer stem cells (CSC). To complicate the
      situation, CSCs interact with the tumor microenvironment, which include cancer
      associated fibroblasts (CAFs), immune cells, endothelial cells, growth factors,
      cytokines and connective tissue components, which via a dynamic crosstalk,
      composed of proteins and exosomes, activates the CSC compartment. In this review,
      we analyze the crosstalk between CSCs and CAFs, the primary component of the
      NSCLC microenvironment, at the molecular and extracellular level and contemplate
      therapies to disrupt this communication.

PMID- 29650270
TI  - Radioiodine refractory differentiated thyroid cancer.
AB  - Differentiated thyroid cancer (DTC) is usually curable with surgery, radioactive
      iodine (RAI), and thyroid-stimulating hormone (TSH) suppression. However, local
      recurrence and/or distant metastases occur in approximately 15% of cases during
      follow-up, and nearly two-thirds of these patients will become RAI-refractory (RR
      DTC) with a poor prognosis. This review focuses on the most challenging and
      rapidly evolving aspects of RR-DTC, and we discuss the considerable improvement
      in more accurately defining RR-DTC, more effective therapeutic strategies, and
      describe the diagnosis, pathogenesis, and future prospects of RR-DTC. Along with
      the detection of serum thyroglobulin and anatomic imaging modalities, such as
      ultrasound and computer tomography, radionuclide molecular imaging plays a vital
      role in the evaluation of RR-DTC. In addition, continual progress has been made
      in the management of RR-DTC, including watchful waiting under appropriate TSH
      suppression, local treatment approaches, and systemic therapies (molecular
      targeted therapy, redifferentiation therapy, gene therapy, and cancer
      immunotherapy). These all hold promise to change the natural history of RR-DTC.

PMID- 29650271
TI  - Effect of anticoagulants on admission rates and length of hospital stay for acute
      venous thromboembolism: A systematic review of randomized control trials.
AB  - BACKGROUND: There is a paucity of data available on hospitalization and length of
      stay (LOS) for different anticoagulant therapies. We sought to compare and
      summarize admission rates and LOS, and describe the frequency of reporting these
      two outcomes in randomized control trials (RCTs) comparing different
      anticoagulant therapies for venous thromboembolism (VTE). METHODS: A literature
      search was conducted from inception to August 15, 2016 on RCTs of anticoagulant
      therapy for patients with VTE. Study selection, data extraction and risk of bias
      analysis were done by two reviewers independently. Meta-analyses were conducted
      for admission rates and LOS. RESULTS: A total of 4064 articles were identified.
      There were 74 articles of 70 studies included in the analysis. Hospitalization
      rates and LOS were reported in 13 (18.6%) and 12 (17.1%) of the 70 included
      studies, respectively. Low-molecular-weight heparin (LMWH)-treated patients were
      33.0% less likely to be admitted to hospitals compared to unfractionated heparin
      (UFH) (RR = 0.67, 95% CI [0.58, 0.78]). The mean difference in LOS between LMWH
      and UFH was 2.54 days in favor of LMWH (95% CI [-4.94, -0.14]). Compared to
      parenteral therapy, using rivaroxaban was associated with a lower admission rate
      for a difference of 1.4-5.1% in VTE, 2.5% in DVT and 0.2% in PE. The LOS of
      patients receiving rivaroxaban was significant shorter than the LOS in parenteral
      therapy group for a difference of 1-5 days in VTE, 3 days in DVT and 1 day in PE.
      CONCLUSION: Admission rates were lower and LOS was shorter using LMWH compared to
      UFH and oral therapy compared to parenteral therapy for acute VTE treatment in
      RCTs, based on limited eligible RCTs. These crucial clinically relevant outcomes
      are underreported in the existing VTE clinical trials.

PMID- 29650272
TI  - Treatment of spinal metastases in renal cell carcinoma: A critical review.
AB  - Kidney cancer is the 9th most common cancer in men and the 14th most common in
      women worldwide. Renal cell carcinoma (RCC) constitutes 90% of all malignancies
      of the kidney. RCC, is known to be highly vascular and relatively radioresistant.
      Bone metastases are one of the most common metastatic sites and occur in around
      30% of RCCs. They significantly impact the quality of life of patients causing
      pain and pathological fractures. Spinal metastases represent a particular case
      with regard to symptoms and treatment. Indeed, neurological pain is often added
      to the nociceptive pain caused by metastases. More importantly, neurological
      impairment can be seen, caused by spinal cord or nerve root compression (MSCC).
      Due to close contact with the spinal cord, the treatment of spinal bone
      metastases is challenging and requires a multidisciplinary approach. Specific
      treatment is currently focused on 4 main avenues which are surgery, radiotherapy,
      interventional radiology and systemic treatment. In June 2017 we carried out an
      extensive search on PubMed, Web of Science, and Cochrane Library to review the
      various treatment options and to establish a treatment strategy. This article
      presents the result of our critical review of the literature, given our expertise
      in the field.

PMID- 29650273
TI  - Dose-dense weekly chemotherapy in advanced ovarian cancer: An updated meta
      analysis of randomized controlled trials.
AB  - OBJECTIVE: The use of dose-dense weekly chemotherapy in the management of
      advanced ovarian cancer (OC) remains controversial. The aim of this meta-analysis
      was to evaluate the efficacy of dose-dense regimen to improve clinical outcomes
      in OC patients with the inclusion of new trials. METHODS: For this updated meta
      analysis, PubMed Medline and Scopus databases and meeting proceedings were
      searched for eligible studies with the limitation of randomized controlled
      trials, comparing dose-dense chemotherapy versus standard treatment. Trials were
      grouped in two types of dose-dense chemotherapy: weekly dose-dense (both
      paclitaxel and carboplatin weekly administration) and semi-weekly dose-dense
      (weekly paclitaxel and three weekly carboplatin administration). Data were
      extracted independently and were analyzed using RevMan statistical software
      version 5.3 (http://www.cochrane.org). Primary end-point was progression-free
      survival (PFS). RESULTS: Four randomized controlled trials comprising 3698
      patients were identified as eligible. Dose-dense chemotherapy had not a
      significant benefit on PFS (HR 0.92, 95% CI 0.81-1.04, p = 0.20). When the
      analysis was restricted to both weekly and semi-weekly dose-dense data, a no
      significant interaction between dose-dense and standard regimen was confirmed (HR
      1.01, 95% CI 0.93-1.10 and HR 0.82, 95% CI 0.63-1.08, respectively). CONCLUSIONS:
      In the absence of PFS superiority of dose-dense schedule, three weekly schedule
      should remain the standard of care for advanced OC.

PMID- 29650274
TI  - Oral cancer in Fanconi anemia: Review of 121 cases.
AB  - Fanconi anemia (FA) is a rare autosomal recessive genetic disorder characterized
      by aplastic anemia, progressive pancytopenia, congenital anomalies, and increased
      risk of cancer development. After hematopoietic stem cell transplant (HSCT),
      patients have an estimated 500-fold increase in the risk of developing head and
      neck cancer compared to a non-affected, and the oral cavity is affected in one
      third of cases. Thus, this study aimed to better understand the natural history
      of oral cavity cancer in patients affected by FA. After conducting a keyword
      search on MEDLINE, we found 121 cases of oral cavity cancer in patients who had
      been affected by FA. In conclusion, HSCT may increase the risks of oral cancer
      development, especially after 5 years after the transplant. In the normal
      population, the tongue is the most affected area. FA patients should be informed
      of the risks of oral malignant transformation and encouraged to be undergo
      medical surveillance.

PMID- 29650275
TI  - Metformin for non-small cell lung cancer patients: Opportunities and pitfalls.
AB  - Despite exciting advances of the anticancer armamentarium in the recent years,
      mortality of non-small cell lung cancer (NSCLC) remains high and novel treatments
      are requisite. Therapy intensification is explored with promising, but expensive
      and potentially toxic new compounds. Repositioning already existing drugs for
      cancer treatment could save money and improve patient outcomes in specific
      contexts. Observational data suggest that use of the standard antidiabetic agent
      metformin decreases lung cancer incidence and mortality. Several basic researches
      have shown various anticancer effects of metformin, acting both on the glycolytic
      metabolism and on the tumoral immune microenvironment. Synergistic actions of
      metformin with antitumoral agents in preclinical NSCLC models have then been
      highlighted. Recent retrospective studies advocated improved outcomes in NSCLC
      diabetic patients receiving metformin with chemoradiotherapy or systemic
      compounds (including conventional platinum-based chemotherapy and EGFR tyrosine
      kinase inhibitors). Several prospective randomized trials are therefore currently
      assessing the addition of metformin to standard therapy in non-diabetic lung
      cancer patients. This article reviews promises and possible limitations of
      concurrent metformin used as an anticancer agent in NSCLC patients.

PMID- 29650276
TI  - Classic biphasic pulmonary blastoma: A case report and review of the literature.
AB  - Pulmonary blastomas represent about 0.5% of primary pulmonary malignancies. The
      prognosis is poor. Standard treatment consists of surgical excision. There are no
      published series on which to judge the efficacy of chemotherapy or radiation
      therapy. We describe an unusual case of classic biphasic pulmonary blastoma
      (CBPC), with long-term survival despite numerous and varied cancer-related events
      and review the literature. Our 71-year-old Caucasian woman presented with history
      of blood in sputum in 2009. Right lower lobectomy yielded a diagnosis of
      sarcomatoid carcinoma (pneumoblastoma). Unusually, our patient is still alive 7
      years after initial surgery, despite metastatic first relapse after 2 years.
      Metastatic progression was confirmed histologically on three separate occasions
      during the disease course. The patient received a combination of cisplatin (or
      carboplatin) and etoposide on three separate occasions. Molecular biology studies
      of CBPC are needed to identify effective treatments, and a patient registry
      should be created.

PMID- 29650277
TI  - Pharmacogenetics of androgen signaling in prostate cancer: Focus on castration
      resistance and predictive biomarkers of response to treatment.
AB  - Tumor heterogeneity strongly affects the molecular mechanisms driving resistance
      to hormonal therapies in castration-resistant prostate cancer. Since the current
      use of available treatments can be optimized on the basis of the molecular
      profile of tumor, the present review focuses on genetic biomarkers in prostate
      cancer and their application to a personalized treatment.

PMID- 29650278
TI  - Circulating tumor cells count as a predictor of survival in lung cancer.
AB  - The presence of circulating tumor cells (CTCs) in the peripheral blood of cancer
      patients was first described in the second half of the 19th century, but research
      interest in their potential clinical utility has intensified and greatly expanded
      only in recent years. Herein, we summarize and critically discuss current
      knowledge on CTC count as a predictor of survival in lung cancer, and comment on
      the existing challenges and future perspectives in this field. The majority of
      data published to date, including the results of almost all large cohorts, are
      strongly supportive of the value of CTC enumeration as a predictor of survival,
      mainly in advanced/metastatic non-small and small cell lung cancer (NSCLC and
      SCLC, respectively). Nonetheless, additional research is warranted to establish
      the prognostic relevance of CTC count in other clinical settings, mainly
      encompassing earlier-stage disease as well as specific molecular subtypes of
      NSCLC (e.g. EGFR mutation-positive or ALK-positive cases).

PMID- 29650279
TI  - The best strategy for RAS wild-type metastatic colorectal cancer patients in
      first-line treatment: A classic and Bayesian meta-analysis.
AB  - BACKGROUND: At present, there is uncertainty on the best systemic treatment in
      first-line setting for RAS wild-type (WT) metastatic colorectal cancer (mCRC)
      patients. Indeed, several chemotherapy and biologics combinations showed an
      improvement on survival. We performed a systematic review with a pair-wise and
      bayesan meta-analysis to rank the best strategy for these patients. METHODS: A
      systematic literature search through March 2017 was performed to evaluate the
      association between several treatment combinations and overall survival (OS),
      progression-free survival (PFS), overall response rate (ORR) and toxicity rate
      (TR) in RAS WT mCRC patients. Data were extracted from studies and pooled using
      the random-effect model for pair-wise meta-analyses and bayesan model for network
      meta-analysis (NMA). RESULTS: Eight studies with a total of 2518 individuals were
      included in the meta-analyses. Pooled analyses for subgroups stratified by type
      of schedule and tumor location demonstrated that anti-EGFR + doublet had the best
      OS when compared to doublet +/- bevacizumab (0.767; 95%CI, 0.695-0.846; P <
      0.0001). This benefit is limited to LSCC when compared to a doublet-based
      schedule and doublet + bevacizumab (HRs, 0.692; 95%CI, 0.596-0.804; P < 0.001;
      0.706; 95%CI, 0.584-0.854; P < 0.001; respectively). No significant differences
      are detected in PFS, whereas the cetuximab-based regimens showed the highest ORR
      and TR. In NMA our ranking showed the best performance for FOLFOX + panitumumab.
      CONCLUSIONS: Our study indicates that FOLFOX + panitumumab has the major
      probability to provide an improvement of survival with a good safety profile in
      patients with RAS WT mCRC with an added value from selection based on sidedness.

PMID- 29650280
TI  - Evaluation of the quality of the reporting of phase II clinical trials in
      oncology: A systematic review.
AB  - OBJECTIVE: To describe the current state of knowledge concerning the quality of
      reporting in phase II clinical trials in oncology and to describe the various
      methods published allowing this quality evaluation. METHODS: databases including
      MEDLINE and COCHRANE were searched. Reviews and meta-analyses analyzing the
      quality of the reporting of phase II trials in oncology were included.
      Descriptive analysis of the results was performed. RESULTS: Thirteen publications
      were retained. Only 2 publications adopted a systematic approach of evaluation of
      the quality of reporting by overall scores. The Key Methodological Score (KMS),
      proposed by Grellety et al., gathering 3 items, seemed adapted for such an
      evaluation. A score of 3/3 was found in 16.1% of the 156 phase II trials analysed
      by this score. The other reviews used a qualitative analysis to evaluate the
      reporting, via an analysis of a single criterion, generally the statistical plan
      of the study. This item was considered as having been correctly reported in less
      than 50% of the analysed articles. CONCLUSION: The quality of reporting in phase
      II trials in oncology is a field that has been investigated very little (13
      publications). When it is studied, the estimated level of quality is not
      satisfactory, whatever the method employed. The use of an overall score of
      evaluation is a path which should be pursued, in order to get reliable results.
      It also seems necessary to propose strong recommendations, which would create a
      consensus for the methodology and the reporting of these studies.

PMID- 29650281
TI  - Recent developments and obstacles in the treatment of melanoma with BRAF and MEK
      inhibitors.
AB  - Metastatic melanoma is a least common form of cancer as it accounts only for 1%
      of all cancer cases. But, it is most deadly in nature and is haunting mankind for
      long emotionally as well as economically. The sites for the onset of the disease
      are pigment-producing cells of the skin, mucosa, eye etc. It has the potential to
      spread other sites like subcutaneous tissue, lymph nodes, lungs, liver, bone and
      brain. The United States Food & Drug Administration has approved various drug
      molecules from time to time. The molecules (Dabrafenib-BRAF inhibitor and
      Trametinib-MEK inhibitor) have proved their credentials alone and in combination
      as well. These molecules have demonstrated good results for various end points
      like median progression free survival, overall survival, objective response etc.
      The median progression free survival for patients using dabrafenib and trametinib
      were 5.1 and 4.8 months, respectively (administered singly). It has increased to
      11.4 months in the combination treatment "dabrafenib + trametinib", which is
      approximately 104% and 138% greater than dabrafenib and trametinib treated groups
      alone. Similarly, the overall survival rate and objective response rate for the
      patients administered with "dabrafenib + trametinib" have been increased by 72%
      64%, respectively. All these increments in these parameters were for a short
      period of time as the molecules were unable to withstand the pressure of
      resistance developed in the patients. So, the current review suggests the use of
      BRAF and MEK inhibitors as intermittent therapy along with heat shock protein 90
      (HSP90) molecules.

PMID- 29650282
TI  - Meeting the needs of breast cancer: A nucleolin's perspective.
AB  - A major challenge in the management of breast cancer disease has been the
      development of metastases. Finding new molecular targets and the design of
      targeted therapeutic approaches to improve the overall survival and quality of
      life of these patients is, therefore, of great importance. Nucleolin, which is
      overexpressed in cancer cells and tumor-associated blood vessels, have been
      implicated in various processes supporting tumorigenesis and angiogenesis.
      Additionally, its overexpression has been demonstrated in a variety of human
      neoplasias as an unfavorable prognostic factor, associated with a high risk of
      relapse and low overall survival. Hence, nucleolin has emerged as a relevant
      target for therapeutic intervention in cancer malignancy, including breast
      cancer. This review focus on the contribution of nucleolin for cancer disease and
      on the development of therapeutic strategies targeting this protein. In this
      respect, it also provides a critical analysis about the potential and pitfalls of
      nanomedicine for cancer therapy.

PMID- 29650283
TI  - [Interventions for smoking cessation in 2018].
AB  - Smoking cessation treatments have been proved effective to stop smoking. For
      pharmacological treatments, nicotine replacement therapies (NRT) as well as
      bupropion allow to increase 6 month-abstinence rates by more than 80% in
      comparison with placebo while varenicline prescription doubles success rates in
      the same conditions. These results mean that for 10 smokers who quit with
      placebo, 18 are expected to quit with NRT or bupropion and 28 are expected to
      quit with varenicline. Varenicline is 50% more effective than nicotine patch and
      70% more effective than nicotine gum. Nevertheless, a combination including NRT
      patch and oral nicotine forms is as effective as varenicline, thus leading to
      encourage the prescription of a combination NRT when NRT are chosen. For these
      three pharmacological treatments, cardiovascular as well as neuropsychiatric
      tolerance were not found statistically different from placebo in randomized
      controlled trials. Yet, bupropion prescription leads to an increasing risk of
      seizure (1/1000 to 1/1500). For behavioral treatment, motivational interviewing
      as well as cognitive behavior therapies are been proven to be effective to stop
      smoking but few smokers have access to this treatment. Smoking cessation mobile
      application and smartphone application seem to be promising in terms of
      effectiveness and might be useful to reach more smokers.

PMID- 29650284
TI  - [Home non-invasive ventilation for chronic obstructive pulmonary disease].
AB  - INTRODUCTION: The benefits of long-term non-invasive ventilation (NIV) in the
      management of chronic obstructive pulmonary disease (COPD) patients remain
      controversial. AIM: To analyze the characteristics of COPD patients under home
      NIV and to evaluate its impact among this population. METHODS: We carried out a
      retrospective study between January 2002 and April 2016 of COPD patients under
      long-term NIV at "la Rabta" and the Military Hospital. RESULTS: There were 27
      patients with an average age of 64 and a sex ratio (M/F) of 0.92. Active smoking
      was reported in 96.3%. A persistent hypercapnia following an acute exacerbation
      of COPD with failure to wean the NIV was the main indication of long-term NIV. We
      noted a reduction in hospital admissions in the first year of 60% and in
      intensive care of 83.3% (P<10-3). There was no non-significant decrease of PaCO2
      (4.5mmHg). There was no modification in FEV 1 and in FVC (P>0.05). The survival
      rate was 96.3% at 1 year, 83.3% at 2 years and a median survival of 24 months.
      CONCLUSIONS: Our study suggests that home NIV contributes to the stabilization of
      some COPD patients by reducing the hospitalizations rates for exacerbation. More
      prospective studies are needed to better assess the impact of NIV on survival and
      quality of life and to better define the COPD patients who require NIV.

PMID- 29650286
TI  - Is a Picture Worth a Thousand Monitors? Utility of a Miniature TEE Probe in the
      ICU.

PMID- 29650285
TI  - Physical Activity, Sedentary Behavior, and Retirement: The Multi-Ethnic Study of
      Atherosclerosis.
AB  - INTRODUCTION: Physical activity and sedentary behavior are major risk factors for
      chronic disease. These behaviors may change at retirement, with implications for
      health in later life. The study objective was to describe longitudinal patterns
      of moderate to vigorous and domain-specific physical activity and TV watching by
      retirement status. METHODS: Participants in the Multi-Ethnic Study of
      Atherosclerosis (n=6,814) were recruited from six U.S. communities and were aged
      45-84 years at baseline. Retirement status and frequency and duration of domain
      specific physical activity (recreational walking, transport walking, non-walking
      leisure activity, caregiving, household, occupational/volunteer) and TV watching
      were self-reported at four study exams (2000 to 2012). Fixed effect linear
      regression models were used to describe longitudinal patterns in physical
      activity and TV watching by retirement status overall and stratified by
      socioeconomic position. Analyses were conducted in 2017. RESULTS: Of 4,091 Multi
      Ethnic Study of Atherosclerosis participants not retired at baseline, 1,012 (25%)
      retired during a median of 9 years follow-up. Retirement was associated with a
      10% decrease (95% CI= -15%, -5%) in moderate to vigorous physical activity and
      increases of 13% to 29% in recreational walking, household activity, and TV
      watching. Among people of low socioeconomic position, the magnitude of
      association was larger for moderate to vigorous physical activity. Among people
      of high socioeconomic position, the magnitude of association was larger for non
      walking leisure and household activity. CONCLUSIONS: The retirement transition
      was associated with changes in physical activity and TV watching. To inform
      intervention development, future research is needed on the determinants of
      behavior change after retirement, particularly among individuals of low
      socioeconomic position.

PMID- 29650287
TI  - Structure-activity relationship study of a series of caspase inhibitors
      containing gamma-amino acid moiety for treatment of cholestatic liver disease.
AB  - A series of caspase inhibitors containing gamma-amino acid moiety have been
      synthesized. A systemic study on their structure-activity relationship of anti
      apoptotic cellular activity is presented. These efforts led to the discovery of
      compound 20o as a potent caspase inhibitor, which demonstrated preclinical
      ameliorating total bilirubin efficacy with a significantly improved
      pharmacokinetic profile.

PMID- 29650288
TI  - Duocarmycin SA, a potent antitumor antibiotic, sensitizes glioblastoma cells to
      proton radiation.
AB  - New treatment modalities for glioblastoma multiforme (GBM) are urgently needed.
      Proton therapy is considered one of the most effective forms of radiation therapy
      for GBM. DNA alkylating agents such as temozolomide (TMZ) are known to increase
      the radiosensitivity of GBM to photon radiation. TMZ is a fairly impotent agent,
      while duocarmycin SA (DSA) is an extremely potent cytotoxic agent capable of
      inducing a sequence-selective alkylation of duplex DNA. Here, the effects of sub
      nM concentrations of DSA on the radiosensitivity of a human GBM cell line (U-138)
      to proton irradiation were examined. Radiation sensitivity was determined by
      viability, apoptosis, necrosis and clonogenic assays. DSA concentrations as low
      as 0.001 nM significantly sensitized U-138 cells to proton irradiation. DSA
      demonstrates synergistic cytotoxicity against GBM cells treated with proton
      radiation in vitro, which may represent a novel therapeutic alternative for the
      treatment of GBM.

PMID- 29650289
TI  - Optimization of dipeptidic inhibitors of cathepsin L for improved Toxoplasma
      gondii selectivity and CNS permeability.
AB  - The neurotropic protozoan Toxoplasma gondii is the second leading cause of death
      due to foodborne illness in the US, and has been designated as one of five
      neglected parasitic infections by the Center for Disease Control and Prevention.
      Currently, no treatment options exist for the chronic dormant-phase Toxoplasma
      infection in the central nervous system (CNS). T. gondii cathepsin L (TgCPL) has
      recently been implicated as a novel viable target for the treatment of chronic
      toxoplasmosis. In this study, we report the first body of SAR work aimed at
      developing potent inhibitors of TgCPL with selectivity vs the human cathepsin L.
      Starting from a known inhibitor of human cathepsin L, and guided by structure
      based design, we were able to modulate the selectivity for Toxoplasma vs human
      CPL by nearly 50-fold while modifying physiochemical properties to be more
      favorable for metabolic stability and CNS penetrance. The overall potency of our
      inhibitors towards TgCPL was improved from 2 MUM to as low as 110 nM and we
      successfully demonstrated that an optimized analog 18b is capable of crossing the
      BBB (0.5 brain/plasma). This work is an important first step toward development
      of a CNS-penetrant probe to validate TgCPL as a feasible target for the treatment
      of chronic toxoplasmosis.

PMID- 29650290
TI  - P3-P4 ureas and reverse carbamates as potent HCV NS3 protease inhibitors:
      Effective transposition of the P4 hydrogen bond donor.
AB  - A series of tripeptidic acylsulfonamide inhibitors of HCV NS3 protease were
      prepared that explored structure-activity relationships (SARs) at the P4
      position, and their in vitro and in vivo properties were evaluated. Enhanced
      potency was observed in a series of P4 ureas; however, the PK profiles of these
      analogues were less than optimal. In an effort to overcome the PK shortcomings,
      modifications to the P3-P4 junction were made. This included a strategy in which
      one of the two urea N-H groups was either N-methylated or replaced with an oxygen
      atom. The former approach provided a series of regioisomeric N-methylated ureas
      while the latter gave rise to P4 reverse carbamates, both of which retained
      potent NS3 inhibitory properties while relying upon an alternative H-bond donor
      topology. Details of the SARs and PK profiles of these analogues are provided.

PMID- 29650291
TI  - The synthesis and antistaphylococcal activity of N-sulfonaminoethyloxime
      derivatives of dehydroabietic acid.
AB  - A series of N-sulfonaminoethyloxime derivatives of dehydroabietic acid were
      synthesized and investigated for their antibacterial activity against
      Staphylococcus aureus Newman strain and multidrug-resistant strains (NRS-1, NRS
      70, NRS-100, NRS-108 and NRS-271). Most of the target compounds having chloro,
      bromo, trifluoromethyl phenyl moiety exhibited potent in vitro antistaphylococcal
      activity. The meta-CF3 phenyl derivative T23 showed the highest activity with MIC
      of 0.39-0.78 MUg/mL against S. aureus Newman, while several analogues showed
      similar potent antibacterial activity with MIC values between 0.78 and 1.56
      MUg/mL against five multidrug-resistant S. aureus. The stability of T35 in plasma
      of SD rat and the cellular cytotoxicity were also evaluated.

PMID- 29650292
TI  - Novel compounds that target lipoprotein lipase and mediate growth arrest in acute
      lymphoblastic leukemia.
AB  - Over the past decade, the therapeutic strategies employed to treat B-precursor
      acute lymphoblastic leukemia (ALL) have been progressively successful in treating
      the disease. Unfortunately, the treatment associated dyslipidemia, either acute
      or chronic, is very prevalent and a cause for decreased quality of life in the
      surviving patients. To overcome this hurdle, we tested a series of
      cylopropanecarboxamides, a family demonstrated to target lipid metabolism, for
      their anti-leukemic activity in ALL. Several of the compounds tested showed anti
      proliferative activity, with one, compound 22, inhibiting both Philadelphia
      chromosome negative REH and Philadelphia chromosome positive SupB15 ALL cell
      division. The novel advantage of these compounds is the potential synergy with
      standard chemotherapeutic agents, while concomitantly blunting the emergence of
      dyslipidemia. Thus, the cylopropanecarboxamides represent a novel class of
      compounds that can be potentially used in combination with the present standard
      of-care to limit treatment associated dyslipidemia in ALL patients.

PMID- 29650293
TI  - Quinone skeleton as a new class of irreversible inhibitors against Staphylococcus
      aureus sortase A.
AB  - Sortase A (SrtA) anchors surface proteins to the cell wall and aids biofilm
      formation during infection, which functions as a key virulence factor of
      important Gram-positive pathogens, such as Staphylococcus aureus. At present
      researchers need a way in which to validate whether or not SrtA is a druggable
      target alternative to the conventional antibiotic targets in the mechanism. In
      this study, we performed a high-throughput screening and identified a new class
      of potential inhibitors of S. aureus SrtA, which are derived from natural
      products and contain the quinone skeleton. Compound 283 functions as an
      irreversible inhibitor that covalently alkylates the active site Cys184 of SrtA.
      NMR analysis confirms the direct interaction of the small-molecule inhibitor
      towards SrtA protein. The anchoring of protein A (SpA) to the cell wall and the
      biofilm formation are significantly attenuated when the S. aureus Newman strain
      is cultured in the presence of inhibitor. Our study indicates that compound 283
      could be a potential hit for the development of new anti-virulence agents against
      S. aureus infections by covalently targeting SrtA.

PMID- 29650294
TI  - Increased methylation at an unexplored glucocorticoid responsive element within
      exon 1D of NR3C1 gene is related to anxious-depressive disorders and decreased
      hippocampal connectivity.
AB  - Among the major psychiatric disorders, anxious-depressive disorders stand out as
      one of the more prevalent and more frequently associated with hypothalamic
      pituitary-adrenal (HPA) axis abnormalities. Methylation at the exon 1F of the
      glucocorticoid receptor gene NR3C1 has been associated with both early stress
      exposure and risk for developing a psychiatric disorder; however, other NR3C1
      promoter regions have been underexplored. Exon 1D emerges as a suggestive new
      target in stress-related disorders epigenetically sensitive to early adversity.
      After assessment of 48 monozygotic twin pairs (n=96 subjects) informative for
      lifetime history of anxious-depressive disorders, they were classified as
      concordant, discordant or healthy in function of whether both, one or neither
      twin in each pair had a lifetime diagnosis of anxious-depressive disorders. DNA
      for epigenetic analysis was extracted from peripheral blood. Exon 1F and exon 1D
      CpG-specific methylation was analysed by means of pyrosequencing technology.
      Functional magnetic resonance imaging was available for 54 subjects (n=27 twin
      pairs). Exon 1D CpG-specific methylation within a glucocorticoid responsive
      element (GRE) was correlated with familial burden of anxious-depressive disorders
      (r=0.35, z=2.26, p=0.02). Right hippocampal connectivity was significantly
      associated with CpG-specific GRE methylation (beta=-2.33, t=-2.85, p=0.01). Exon
      1F was uniformly hypomethylated across all subgroups of the present sample. GRE
      hypermethylation at exon 1D of the NR3C1 gene in monozygotic twins concordant for
      anxious-depressive disorders suggests this region plays a role in increasing
      vulnerability to psychosocial stress, partly mediated by altered hippocampal
      connectivity.

PMID- 29650295
TI  - Acquired von Willebrand syndrome and impaired platelet function during venovenous
      extracorporeal membrane oxygenation: Rapid onset and fast recovery.
AB  - BACKGROUND: Bleeding contributes to the high mortality of venovenous
      extracorporeal membrane oxygenation (vvECMO). The development of acquired von
      Willebrand syndrome (AVWS) has been identified as relevant pathology during ECMO.
      This study was performed to determine the onset of AVWS after implantation and
      the recovery of von Willebrand factor (VWF) parameters after explantation of ECMO
      in a large cohort of patients. METHODS: VWF parameters of 59 patients treated
      with vvECMO at a university ECMO center were obtained before ECMO implantation,
      during therapy, and after explantation. In a subgroup of patients, light
      transmission aggregometry of platelets and flow-cytometric quantification of
      platelet granule secretion were performed. RESULTS: All patients developed severe
      AVWS hours after implantation of vvECMO. After explantation, AVWS recovered
      within 3 hours in 60%, within 6 hours in 86%, and in all patients within 1 day.
      Aggregometry showed hypoaggregability of platelets after stimulation with ADP,
      ristocetin, collagen, and epinephrine. Flow-cytometric platelet analyses revealed
      severely reduced expression of CD62 and CD63. CONCLUSIONS: All patients during
      vvECMO support rapidly develop AVWS and platelet dysfunction, resulting in severe
      impairment of coagulation. After explantation, AVWS overwhelmingly recovers
      within hours, resulting in a hypercoagulative state. These findings augment the
      need for novel extracorporeal technologies with reduced shear stress, and shift
      the emphasis for intense anti-coagulation during ECMO instead to a time-point
      after explantation.

PMID- 29650296
TI  - Prognostic usefulness of arm circumference and nutritional screening tools in
      older patients with cardiovascular disease.
AB  - BACKGROUND AND AIM: Arm circumference (AC) and nutritional screening tools have
      been shown to have prognostic capability in patients with cardiovascular disease
      (CVD). This study aimed to compare the prognostic predictive capabilities of AC
      and nutritional screening tools in older patients with CVD. METHODS AND RESULTS:
      The study population consisted of 949 admitted patients >=60 years old with CVD.
      Patients underwent AC measurement and nutritional screening before hospital
      discharge. We used the controlling nutritional status index (CONUT), the
      geriatric nutritional risk index (GNRI), and the prognostic nutritional index
      (PNI) as nutritional screening tools. The end point of the study was all-cause
      mortality. The mean age of the study population was 72.3 +/- 7.2 years, and 68.2%
      of the patients were male. A total of 130 deaths occurred over a median follow-up
      period of 2.2 years (interquartile range, 1.1-3.8 years). After adjusting for
      other prognostic factors, AC (hazard ratio [HR]: 0.59; p < 0.001), CONUT (HR:
      0.82; p = 0.016), GNRI (HR: 0.77; p = 0.040), and PNI (HR: 0.80; p = 0.014) were
      significant predictors of mortality. However, adding AC to the multivariate
      adjusted model (0.739 vs. 0.714, respectively; p = 0.037), but not CONUT, GNRI,
      or PNI (0.724, 0.717, and 0.723 vs. 0.714; p = 0.072, p = 0.306, and p = 0.127,
      respectively), significantly increased the area under the curve on receiver
      operating characteristic curve. CONCLUSIONS: AC, but not nutritional screening
      tools, plays a complementary role to preexisting prognostic factors for
      predicting prognosis in older patients with CVD.

PMID- 29650297
TI  - N-terminal pro B-Type natriuretic peptide is inversely correlated with low
      density lipoprotein cholesterol in the very elderly.
AB  - BACKGROUND AND AIMS: Laboratory studies on human adipose tissue and
      differentiated adipocytes indicate that natriuretic peptides (NPs) affect lipid
      metabolism and plasma cholesterol. Few previous clinical studies in non-elderly
      populations found associations between NPs in the physiological range and
      cholesterol. AIM: evaluate the association between NT-proBNP and lipid profile in
      very elderly hospitalized patients characterized by a wide range of NT-proBNP
      levels. METHODS AND RESULTS: Cross-sectional study on 288 very elderly patients
      hospitalized for medical conditions, in which increased NT-proBNP levels are very
      common. NT-proBNP, total cholesterol (TC), HDL cholesterol (HDLc) and
      triglycerides were collected just few days before discharge. Patients taking
      lipid-lowering drugs and patients with an admission diagnosis of acute heart
      failure were excluded. Calculated LDL-cholesterol (LDLc) was used for the
      analyses. Mean age: 87.7 +/- 6.2 years; female prevalence (57.3%). Median NT
      proBNP: 2949 (1005-7335) pg/ml; mean TC: 145.1 +/- 40.3 mg/dl; mean HDLc: 38.4 +/
      18.6 mg/dl; median triglycerides: 100 (75-129) mg/dl; mean LDLc: 84.0 +/- 29.5
      mg/dl. We found negative correlations between NT-proBNP and both TC and LDLc (Rho
      = -0.157; p = 0.008 and Rho = -0.166; p = 0.005, respectively), while no
      correlations emerged between NT-proBNP and HDLc (Rho = -0.065; p = 0.275) or
      triglycerides (Rho = -0.009; p = 0.874). These associations were confirmed
      considering NT-proBNP tertiles. The inverse association between NT-proBNP and
      LDLc was maintained even after adjusting for confounding factors. CONCLUSION: Our
      real-life clinical study supports the hypothesis that NPs play a role on
      cholesterol metabolism, given the association found between LDLc and NT-proBNP
      even in very elderly patients where NT-proBNP values are often in the
      pathological range.

PMID- 29650298
TI  - Lead extraction from Cathode Ray Tube (CRT) funnel glass: Reaction mechanisms in
      thermal reduction with addition of carbon (C).
AB  - This study quantitatively determined the extraction of lead from CRT funnel glass
      and examined the mechanisms of thermally reducing lead in the products of
      sintering Pb-glass with carbon in the pre-heated furnace. The experimentally
      derived results indicate that a 90.3 wt% lead extraction efficiency can be
      achieved with 20 wt% of C addition at 950  degrees C for 3 min under air. The
      formation of viscous semi-liquid glass blocked the oxygen supply between the
      interaction of C and Pb-glass, and was highly effective for the extraction of
      metallic Pb. A maximum of 87.3% lead recover was obtained with a C to Na2CO3
      ratio of 1/3 at 1200  degrees C. The decrease of C/Na2CO3 ratio enhanced the
      metallic lead recovery by increasing the glass viscosity for effective
      sedimentation of metallic lead in the bottom. However, with the further increase
      of temperature and treatment time, re-vitrification of lead back to silicate
      glass matrix was detected in both Pb-glass/C and Pb-glass/C/Na2CO3 systems. The
      findings indicated that with proper controls, using C as an inexpensive reagent
      can effectively reduce treatment time and energy, which is crucial to a waste-to
      resource technology for economically recovering lead from the waste CRT glass.

PMID- 29650299
TI  - Reporting of complications after laparoscopic cholecystectomy: a systematic
      review.
AB  - BACKGROUND: Consistent measurement and reporting of outcomes, including
      adequately defined complications, is important for the evaluation of surgical
      care and the appraisal of new surgical techniques. The range of complications
      reported after LC has not been evaluated. This study aimed to identify the range
      of complications currently reported for laparoscopic cholecystectomy (LC), and
      the adequacy of their definitions. METHODS: MEDLINE, EMBASE, and the Cochrane
      Central Register of Controlled Trials were searched for prospective studies
      reporting clinical outcomes of LC, between 2013 and 2016. RESULTS: In total 233
      studies were included, reporting 967 complications, of which 204 (21%) were
      defined. One hundred and twenty-two studies (52%) did not provide definitions for
      any of the complications reported. Conversion to open cholecystectomy was the
      most commonly reported complication, reported in 135 (58%) studies, followed by
      bile leak in 89 (38%) and bile duct injury in 75 (32%). Mortality was reported in
      89 studies (38%). CONCLUSION: Considerable variation was identified between
      studies in the choice of measures used to evaluate the complications of LC, and
      in their definitions. A standardised set of core outcomes of LC should be
      developed for use in clinical trials and in evaluating the performance of
      surgical units.

PMID- 29650300
TI  - [Surgical treatment of an auto-immune hemolytic anemia].
AB  - INTRODUCTION: Auto-immune hemolytic anemia (AIHA) is a rare cause of anemia,
      characterized by autoantibodies directed against self red blood cells. It can be
      primary or secondary, in particular due to lymphoproliferative diseases. CASE
      REPORT: We report the case of a 24-year-old woman who presented with a severe
      macrocytic anemia associated with an ovarian teratoma. CONCLUSION: Ovarian
      teratoma is a rare cause of secondary AIHA, with only few cases reported. Its
      treatment differs from primary AIHA as steroids may be ineffective. Indeed,
      complete response can only be achieved with surgical excision of the tumor.

PMID- 29650301
TI  - [Pulmonary intravascular talcosis: A case report].
AB  - INTRODUCTION: Pulmonary intravascular talcosis is a rare condition occurring in
      intravenous drug users injecting oral medications. Talc results in a foreign-body
      granulomatous reaction giving a radiological haematogenic miliary appearance
      mimicking miliary tuberculosis. Drug users represent a population at risk for
      both these conditions and their distinction may be challenging. CASE REPORT: We
      reported the case of a man, 33 year-old, intravenous drug addict, detected by the
      health services because he was the partner of a person who died of contagious and
      multi-resistant tuberculosis. Chest X-ray and CT scan showed a typical miliary
      appearance. Despite negative microbiology, clinical diagnosis of miliary
      tuberculosis was retained. Due to the lack of radiological improvement despite
      appropriate antibiotic treatment, re-evaluation and trans-bronchial biopsy were
      undertaken. The presence of granulomas centered by birefringent foreign bodies in
      polarized light led to a diagnosis of pulmonary intravascular talcosis.
      CONCLUSION: In the presence of pulmonary miliary in an intravenous drug addict,
      intravascular talcosis should be suspected.

PMID- 29650302
TI  - RayStation: External beam treatment planning system.
AB  - RaySearch Laboratories is a world leader in the field of advanced software and
      creator of the RayStation treatment planning system for radiation therapy. The
      aim with RayStation is to deliver an unmatched user experience and leading
      functionality. Unique features described here include multiatlas based
      autosegmentation for contouring, deformable registration with 2 different
      algorithms, multicriteria optimization, Plan Explorer, fallback planning,
      ultrafast computation speed, and 4-dimensional (4D) adaptive radiation therapy.
      RayStation can be used to plan for electrons and photons on traditional linacs,
      for protons on various delivery systems, and for Accuray's helical TomoTherapy
      system. This paper describes some of these modalities, with reference to clinical
      cases and including descriptions of the impact on workflow.

PMID- 29650303
TI  - Generating region proposals for histopathological whole slide image retrieval.
AB  - BACKGROUND AND OBJECTIVE: Content-based image retrieval is an effective method
      for histopathological image analysis. However, given a database of huge whole
      slide images (WSIs), acquiring appropriate region-of-interests (ROIs) for
      training is significant and difficult. Moreover, histopathological images can
      only be annotated by pathologists, resulting in the lack of labeling information.
      Therefore, it is an important and challenging task to generate ROIs from WSI and
      retrieve image with few labels. METHODS: This paper presents a novel unsupervised
      region proposing method for histopathological WSI based on Selective Search.
      Specifically, the WSI is over-segmented into regions which are hierarchically
      merged until the WSI becomes a single region. Nucleus-oriented similarity
      measures for region mergence and Nucleus-Cytoplasm color space for
      histopathological image are specially defined to generate accurate region
      proposals. Additionally, we propose a new semi-supervised hashing method for
      image retrieval. The semantic features of images are extracted with Latent
      Dirichlet Allocation and transformed into binary hashing codes with Supervised
      Hashing. RESULTS: The methods are tested on a large-scale multi-class database of
      breast histopathological WSIs. The results demonstrate that for one WSI, our
      region proposing method can generate 7.3 thousand contoured regions which fit
      well with 95.8% of the ROIs annotated by pathologists. The proposed hashing
      method can retrieve a query image among 136 thousand images in 0.29 s and reach
      precision of 91% with only 10% of images labeled. CONCLUSIONS: The unsupervised
      region proposing method can generate regions as predictions of lesions in
      histopathological WSI. The region proposals can also serve as the training
      samples to train machine-learning models for image retrieval. The proposed
      hashing method can achieve fast and precise image retrieval with small amount of
      labels. Furthermore, the proposed methods can be potentially applied in online
      computer-aided-diagnosis systems.

PMID- 29650304
TI  - The design and validation of a hybrid digital-signal-processing plug-in for
      traditional cochlear implant speech processors.
AB  - BACKGROUND AND OBJECTIVE: Cochlear implants (CIs) are electronic devices
      restoring partial hearing to deaf individuals with profound hearing loss. In this
      paper, a new plug-in for traditional IIR filter-banks (FBs) is presented for
      cochlear implants based on wavelet neural networks (WNNs). Having provided such a
      plug-in for commercially available CIs, it is possible not only to use available
      hardware in the market but also to optimize their performance compared with the
      state-of-the-art. METHODS: An online database of Dutch diphone perception was
      used in our study. The weights of the WNNs were tuned using particle swarm
      optimization (PSO) on a training set (speech-shaped noise (SSN) of 2 dB SNR),
      while its performance was assessed on a test set in terms of objective and
      composite measures in the hold-out validation framework. The cost function was
      defined based on the combination of mean square error (MSE), short-time objective
      intelligibility (STOI) criteria on the training set. Variety of performance
      indices were used including segmental signal- to -noise ratio (SNRseg), MSE,
      STOI, log-likelihood ratio (LLR), weighted spectral slope (WSS), and composite
      measures Csig,Cbak and Covl. Meanwhile, the following CI speech processing
      techniques were used for comparison: traditional FBs, dual resonance nonlinear
      (DRNL) and simple dual path nonlinear (SPDN) models. RESULTS: The average SNRseg,
      MSE, and LLR values for the WNN in the entire data set were 2.496 +/- 2.794,
      0.086 +/- 0.025 and 2.323 +/- 0.281, respectively. The proposed method
      significantly improved MSE, SNR, SNRseg, LLR, Csig Cbak and Covl compared with
      the other three methods (repeated-measures analysis of variance (ANOVA); P <
      0.05). The average running time of the proposed algorithm (written in Matlab
      R2013a) on the training and test sets for each consonant or vowel on an Intel
      dual-core 2.10 GHz CPU with 2GB of RAM was 9.91 +/- 0.87 (s) and 0.19 +/- 0.01
      (s), respectively. CONCLUSIONS: The proposed algorithm is accurate and precise
      and is thus a promising new plug-in for traditional CIs. Although the tuned
      algorithm is relatively fast, it is necessary to use efficient vectorized
      implementations for real-time CI speech signal processing.

PMID- 29650305
TI  - Encryption and watermark-treated medical image against hacking disease-An immune
      convention in spatial and frequency domains.
AB  - Digital Imaging and Communications in Medicine (DICOM) is one among the
      significant formats used worldwide for the representation of medical images.
      Undoubtedly, medical-image security plays a crucial role in telemedicine
      applications. Merging encryption and watermarking in medical-image protection
      paves the way for enhancing the authentication and safer transmission over open
      channels. In this context, the present work on DICOM image encryption has
      employed a fuzzy chaotic map for encryption and the Discrete Wavelet Transform
      (DWT) for watermarking. The proposed approach overcomes the limitation of the
      Arnold transform-one of the most utilised confusion mechanisms in image
      ciphering. Various metrics have substantiated the effectiveness of the proposed
      medical-image encryption algorithm.

PMID- 29650306
TI  - Multichannel lung sound analysis for asthma detection.
AB  - BACKGROUND AND OBJECTIVE: Lung sound signals convey valuable information of the
      lung status. Auscultation is an effective technique to appreciate the condition
      of the respiratory system using lung sound signals. The prior works on asthma
      detection from lung sound signals rely on the presence of wheeze. In this paper,
      we have classified normal and asthmatic subjects using advanced signal processing
      of posterior lung sound signals, even in the absence of wheeze. METHODS: We
      collected lung sounds of 60 subjects (30 normal and 30 asthma) using a novel 4
      channel data acquisition system from four different positions over the posterior
      chest, as suggested by the pulmonologist. A spectral subband based feature
      extraction scheme is proposed that works with artificial neural network (ANN) and
      support vector machine (SVM) classifiers for the multichannel signal. The power
      spectral density (PSD) is estimated from extracted lung sound cycle using Welch's
      method, which then decomposed into uniform subbands. A set of statistical
      features is computed from each subband and applied to ANN and SVM classifiers to
      classify normal and asthmatic subjects. RESULTS: In the first part of this study,
      the performances of each individual channel and four channels together are
      evaluated where the combined channel performance is found superior to that of
      individual channels. Next, the performances of all possible combinations of the
      channels are investigated and the best classification accuracies of 89.2( +/-
      3.87)% and 93.3( +/- 3.10)% are achieved for 2-channel and 3-channel combinations
      in ANN and SVM classifiers, respectively. CONCLUSIONS: The proposed multichannel
      asthma detection method where the presence of wheeze in lung sound is not a
      necessary requirement, outperforms commonly used lung sound classification
      methods in this field and provides significant relative improvement. The channel
      combination study gives insight into the contribution of respective lung sound
      collection areas and their combinations in asthma detection.

PMID- 29650307
TI  - Development of an information retrieval tool for biomedical patents.
AB  - BACKGROUND AND OBJECTIVE: The volume of biomedical literature has been increasing
      in the last years. Patent documents have also followed this trend, being
      important sources of biomedical knowledge, technical details and curated data,
      which are put together along the granting process. The field of Biomedical text
      mining (BioTM) has been creating solutions for the problems posed by the
      unstructured nature of natural language, which makes the search of information a
      challenging task. Several BioTM techniques can be applied to patents. From those,
      Information Retrieval (IR) includes processes where relevant data are obtained
      from collections of documents. In this work, the main goal was to build a patent
      pipeline addressing IR tasks over patent repositories to make these documents
      amenable to BioTM tasks. METHODS: The pipeline was developed within @Note2, an
      open-source computational framework for BioTM, adding a number of modules to the
      core libraries, including patent metadata and full text retrieval, PDF to text
      conversion and optical character recognition. Also, user interfaces were
      developed for the main operations materialized in a new @Note2 plug-in. RESULTS:
      The integration of these tools in @Note2 opens opportunities to run BioTM tools
      over patent texts, including tasks from Information Extraction, such as Named
      Entity Recognition or Relation Extraction. We demonstrated the pipeline's main
      functions with a case study, using an available benchmark dataset from
      BioCreative challenges. Also, we show the use of the plug-in with a user query
      related to the production of vanillin. CONCLUSIONS: This work makes available all
      the relevant content from patents to the scientific community, decreasing
      drastically the time required for this task, and provides graphical interfaces to
      ease the use of these tools.

PMID- 29650308
TI  - The impact of social media-based support groups on smoking relapse prevention in
      Saudi Arabia.
AB  - BACKGROUND AND OBJECTIVE: Tobacco smoking remains a major preventable cause of
      mortality and morbidity across the globe. People who attempt to quit smoking
      often experience episodes of relapse before finally quitting. Understanding the
      part that social networking sites and social media can play in smoking cessation
      and prevention of relapse is important to aid the development of novel techniques
      to curb the smoking epidemic. This study investigated the use of extra-treatment
      provided outside of the formal healthcare setting, bolstered by online social
      support in order to prevent smoking relapse in Saudi Arabia. METHODS: This cross
      sectional study included 473 smokers taking part in smoking cessation
      intervention programs run by the Riyadh branch of King Abdul-Aziz Medical City
      and PURITY, a Saudi anti-smoking association. Only subjects who expressed an
      interest in quitting smoking, and those attempting to quit, were considered for
      inclusion. The sample was divided into three groups: subjects who subscribed to
      support groups on Twitter (n = 150), and WhatsApp (n = 150), and a control group
      of subjects who had not subscribed to any social media support groups (n = 173).
      RESULTS: A significant difference was found between the mean average numbers of
      people who quit smoking among the three groups, with social media support proving
      to be more effective than other traditional methods. Our findings imply that
      Twitter and WhatsApp users found it easier to quit smoking than those who did not
      take part in these social media groups. CONCLUSION: Social media provides a good
      platform to discuss smoking cessation treatment, and thus reduce smoking
      relapses. Our findings support the suggestion that more social media support
      groups should be developed to help people to effectively cease smoking after
      abstinence. Individuals who struggle to quit smoking should be encouraged to join
      support groups on their social media platform of choice to increase their
      likelihood of quitting. Future studies should assess the effectiveness of social
      media to help people quit smoking by including a greater diversity of social
      media platforms, including Facebook, Snapchat, and Instagram.

PMID- 29650309
TI  - Open-loop glucose control: Automatic IOB-based super-bolus feature for commercial
      insulin pumps.
AB  - BACKGROUND AND OBJECTIVE: Although there has been significant progress towards
      closed-loop type 1 diabetes mellitus (T1DM) treatments, most diabetic patients
      still treat this metabolic disorder in an open-loop manner, based on insulin pump
      therapy (basal and bolus insulin infusion). This paper presents a method for
      automatic insulin bolus shaping based on insulin-on-board (IOB) as an alternative
      to conventional bolus dosing. METHODS: The methodology presented allows the pump
      to generate the so-called super-bolus (SB) employing a two-compartment IOB
      dynamic model. The extra amount of insulin to boost the bolus and the basal
      cutoff time are computed using the duration of insulin action (DIA). In this way,
      the pump automatically re-establishes basal insulin when IOB reaches its basal
      level. Thus, detrimental transients caused by manual or a-priori computations are
      avoided. RESULTS: The potential of this method is illustrated via in-silico
      trials over a 30 patients cohort in single meal and single day scenarios. In the
      first ones, improvements were found (standard treatment vs. automatic SB) both in
      percentage time in euglycemia (75g meal: 81.9 +/- 15.59 vs. 89.51 +/- 11.95, rho
      ? 0; 100g meal: 75.12 +/- 18.23 vs. 85.46 +/- 14.96, rho ? 0) and time in
      hypoglecymia (75g meal: 5.92 +/- 14.48 vs. 0.97 +/- 4.15, rho=0.008; 100g meal:
      9.5 +/- 17.02 vs. 1.85 +/- 7.05, rho=0.014). In a single day scenario,
      considering intra-patient variability, the time in hypoglycemia was reduced (9.57
      +/- 14.48 vs. 4.21 +/- 6.18, rho=0.028) and improved the time in euglycemia
      (79.46 +/- 17.46 vs. 86.29 +/- 11.73, rho=0.007). CONCLUSIONS: The automatic IOB
      based SB has the potential of a better performance in comparison with the
      standard treatment, particularly for high glycemic index meals with high
      carbohydrate content. Both glucose excursion and time spent in hypoglycemia were
      reduced.

PMID- 29650310
TI  - Electronic health record with computerized decision support tools for the
      purposes of a pediatric cardiovascular heart disease screening program in Crete.
AB  - BACKGROUND AND OBJECTIVE: Early detection of cardiovascular (CV) disease or
      associated risk factors during childhood is of paramount importance, allowing for
      early treatment or lifestyle modifications, respectively. The objective of this
      study was to describe the development of an electronic health record (EHR), with
      integrated computerized decision support system (CDSS), specifically designed for
      supporting the needs of a pilot pediatric CV disease screening program applied on
      primary school students of a Mediterranean island. METHODS: Evidence-based
      knowledge, national and international practice guidelines regarding sport
      preparticipation CV screening of children and young athletes has been used for
      the design of the designated EHR. A CDSS, capable for providing alerts for
      further cardiology evaluation need, has been incorporated into the EHR, based on
      normative anthropometric and electrocardiographic data as well as predefined
      positive history responses. RESULTS: We developed a designated EHR with
      integrated CDSS supporting pediatric CV disease screening, capable for
      documenting CV-related personal and family history responses, physical evaluation
      data (weight, height, blood pressure), allowing for entering electrocardiogam
      (ECG) measurements and for uploading of multimedia files (including ECG images
      and digital phonocardiogram audio files). The EHR incorporates clinical
      calculators and referral alerts for the presence (and degree) of adiposity,
      hypertension, ECG abnormalities and positive history responses indicative of high
      CV disease risk. In a preliminary EHR validation, performed by entering data from
      53 previously available paper-based health records, the EHR was proven to be
      fully functional. CONCLUSIONS: The pediatric cardiology EHR with CDSS features
      which we developed might serve as a model for EHR for primary health care
      purposes, capable to document and early detect CV disease and associated risk
      factors in pediatric populations.

PMID- 29650311
TI  - An object-oriented computational model to study cardiopulmonary hemodynamic
      interactions in humans.
AB  - BACKGROUND AND OBJECTIVE: This work introduces an object-oriented computational
      model to study cardiopulmonary interactions in humans. METHODS: Modeling was
      performed in object-oriented programing language Matlab Simscape, where model
      components are connected with each other through physical connections.
      Constitutive and phenomenological equations of model elements are implemented
      based on their non-linear pressure-volume or pressure-flow relationship. The
      model includes more than 30 physiological compartments, which belong either to
      the cardiovascular or respiratory system. The model considers non-linear
      behaviors of veins, pulmonary capillaries, collapsible airways, alveoli, and the
      chest wall. Model parameters were derisved based on literature values. Model
      validation was performed by comparing simulation results with clinical and animal
      data reported in literature. RESULTS: The model is able to provide quantitative
      values of alveolar, pleural, interstitial, aortic and ventricular pressures, as
      well as heart and lung volumes during spontaneous breathing and mechanical
      ventilation. Results of baseline simulation demonstrate the consistency of the
      assigned parameters. Simulation results during mechanical ventilation with PEEP
      trials can be directly compared with animal and clinical data given in
      literature. CONCLUSIONS: Object-oriented programming languages can be used to
      model interconnected systems including model non-linearities. The model provides
      a useful tool to investigate cardiopulmonary activity during spontaneous
      breathing and mechanical ventilation.

PMID- 29650312
TI  - Tree-based models for survival data with competing risks.
AB  - OBJECTIVE: Tree-based models belong to common, assumption-free methods of data
      analysis. Their application in survival data is narrowed to univariate models,
      which partition the feature space with axis-parallel hyperplanes, meaning that
      each internal node involves a single feature. In this paper, I extend the idea of
      oblique survival tree induction for competing risks by modifying a piecewise
      linear criterion function. Additionally, the use of tree-based ensembles to
      analyze the competing events is proposed. METHOD AND MATERIALS: Two types of
      competing risks trees are proposed: a single event tree designed for analysis of
      the event of interest and a composite event tree, in which all the competing
      events are taken into account. The induction process is similar, except that the
      calculation of the criterion function is minimized for the individual tree nodes
      generation. These two tree types were also used for building the ensembles with
      aggregated cumulative incidence functions as an outcome. Nine real data sets, as
      well as a simulated data set, were taken to assess performance of the models,
      while detailed analysis was conducted on the basis of follicular cell lymphoma
      data. RESULTS: The evaluation was focused on two measures: the prediction error
      expressed by an integrated Brier score (IBS), and the ranked measure of
      predictive ability calculated as a time-truncated concordance index (C-index).
      The proposed techniques were compared with the existing approaches of the Fine
      Gray subdistribution hazard model, Fine-Gray regression model with backward
      elimination, and random survival forest for competing risks. The results for both
      the IBS and the C-index indicated statistically significant differences between
      these methods (p < .0001). CONCLUSIONS: The prediction error of the individual
      trees was similar to the other methods, but the results of the C-index differ in
      comparison to the Fine-Gray subdistribution hazard model and the Fine-Gray
      regression with backward elimination. The ensembles prediction ability was
      comparable to existing algorithms, but their IBS values were better than either
      random survival forest or Fine-Gray regression with backward elimination.

PMID- 29650313
TI  - A novel feature extraction technique for pulmonary sound analysis based on EMD.
AB  - BACKGROUND AND OBJECTIVE: The stethoscope based auscultation technique is a
      primary diagnostic tool for chest sound analysis. However, the performance of
      this method is limited due to its dependency on physicians experience, knowledge
      and also clarity of the signal. To overcome this problem we need an automated
      computer-aided diagnostic system that will be competent in noisy environment. In
      this paper, a novel feature extraction technique is introduced for discriminating
      various pulmonary dysfunctions in an automated way based on pattern recognition
      algorithms. METHOD: In this work, the disease correlated relevant characteristics
      of lung sounds signals are identified in terms of statistical distribution
      parameters: mean, variance, skewness, and kurtosis. These features are extracted
      from selective morphological components of the mapped signal in the empirical
      mode decomposition domain. The feature set is fed to the classifier model to
      differentiate their corresponding classes. RESULTS: The significance of features
      developed are validated by conducting several experiments using supervised and
      unsupervised classifiers. Furthermore, the discriminating power of the proposed
      features is compared with three types of baseline features. The experimental
      result is evaluated by statistical analysis and also validated with physicians
      inference. CONCLUSIONS: It is found that the proposed features extraction
      technique is superior to the baseline methods in terms of classification
      accuracy, sensitivity and specificity. The developed method gives better results
      compared to baseline methods in any circumstance. The proposed method gives a
      higher accuracy of 94.16, sensitivity of 100 and specificity of 93.75 for an
      artificial neural network classifier.

PMID- 29650314
TI  - A topo-graph model for indistinct target boundary definition from anatomical
      images.
AB  - BACKGROUND AND OBJECTIVE: It can be challenging to delineate the target object in
      anatomical imaging when the object boundaries are difficult to discern due to the
      low contrast or overlapping intensity distributions from adjacent tissues.
      METHODS: We propose a topo-graph model to address this issue. The first step is
      to extract a topographic representation that reflects multiple levels of
      topographic information in an input image. We then define two types of node
      connections - nesting branches (NBs) and geodesic edges (GEs). NBs connect nodes
      corresponding to initial topographic regions and GEs link the nodes at a detailed
      level. The weights for NBs are defined to measure the similarity of regional
      appearance, and weights for GEs are defined with geodesic and local constraints.
      NBs contribute to the separation of topographic regions and the GEs assist the
      delineation of uncertain boundaries. Final segmentation is achieved by
      calculating the relevance of the unlabeled nodes to the labels by the
      optimization of a graph-based energy function. We test our model on 47 low
      contrast CT studies of patients with non-small cell lung cancer (NSCLC), 10
      contrast-enhanced CT liver cases and 50 breast and abdominal ultrasound images.
      The validation criteria are the Dice's similarity coefficient and the Hausdorff
      distance. RESULTS: Student's t-test show that our model outperformed the graph
      models with pixel-only, pixel and regional, neighboring and radial connections (p
      values <0.05). CONCLUSIONS: Our findings show that the topographic representation
      and topo-graph model provides improved delineation and separation of objects from
      adjacent tissues compared to the tested models.

PMID- 29650315
TI  - Radiomics-based features for pattern recognition of lung cancer histopathology
      and metastases.
AB  - BACKGROUND AND OBJECTIVES: lung cancer is the leading cause of cancer-related
      deaths in the world, and its poor prognosis varies markedly according to tumor
      staging. Computed tomography (CT) is the imaging modality of choice for lung
      cancer evaluation, being used for diagnosis and clinical staging. Besides tumor
      stage, other features, like histopathological subtype, can also add prognostic
      information. In this work, radiomics-based CT features were used to predict lung
      cancer histopathology and metastases using machine learning models. METHODS:
      local image datasets of confirmed primary malignant pulmonary tumors were
      retrospectively evaluated for testing and validation. CT images acquired with
      same protocol were semiautomatically segmented. Tumors were characterized by
      clinical features and computer attributes of intensity, histogram, texture,
      shape, and volume. Three machine learning classifiers used up to 100 selected
      features to perform the analysis. RESULTS: radiomics-based features yielded areas
      under the receiver operating characteristic curve of 0.89, 0.97, and 0.92 at
      testing and 0.75, 0.71, and 0.81 at validation for lymph nodal metastasis,
      distant metastasis, and histopathology pattern recognition, respectively.
      CONCLUSIONS: the radiomics characterization approach presented great potential to
      be used in a computational model to aid lung cancer histopathological subtype
      diagnosis as a "virtual biopsy" and metastatic prediction for therapy decision
      support without the necessity of a whole-body imaging scanning.

PMID- 29650316
TI  - SeeSway - A free web-based system for analysing and exploring standing balance
      data.
AB  - BACKGROUND AND OBJECTIVES: Computerised posturography can be used to assess
      standing balance, and can predict poor functional outcomes in many clinical
      populations. A key limitation is the disparate signal filtering and analysis
      techniques, with many methods requiring custom computer programs. This paper
      discusses the creation of a freely available web-based software program, SeeSway
      (www.rehabtools.org/seesway), which was designed to provide powerful tools for
      pre-processing, analysing and visualising standing balance data in an easy to use
      and platform independent website. METHODS: SeeSway links an interactive web
      platform with file upload capability to software systems including LabVIEW,
      Matlab, Python and R to perform the data filtering, analysis and visualisation of
      standing balance data. Input data can consist of any signal that comprises an
      anterior-posterior and medial-lateral coordinate trace such as center of pressure
      or mass displacement. This allows it to be used with systems including criterion
      reference commercial force platforms and three dimensional motion analysis,
      smartphones, accelerometers and low-cost technology such as Nintendo Wii Balance
      Board and Microsoft Kinect. Filtering options include Butterworth, weighted and
      unweighted moving average, and discrete wavelet transforms. Analysis methods
      include standard techniques such as path length, amplitude, and root mean square
      in addition to less common but potentially promising methods such as sample
      entropy, detrended fluctuation analysis and multiresolution wavelet analysis.
      These data are visualised using scalograms, which chart the change in frequency
      content over time, scatterplots and standard line charts. This provides the user
      with a detailed understanding of their results, and how their different pre
      processing and analysis method selections affect their findings. RESULTS: An
      example of the data analysis techniques is provided in the paper, with graphical
      representation of how advanced analysis methods can better discriminate between
      someone with neurological impairment and a healthy control. CONCLUSIONS: The goal
      of SeeSway is to provide a simple yet powerful educational and research tool to
      explore how standing balance is affected in aging and clinical populations.

PMID- 29650317
TI  - Monte-Carlo based assessment of MAGIC, MAGICAUG, PAGATUG and PAGATAUG polymer gel
      dosimeters for ovaries and uterus organ dosimetry in brachytherapy, nuclear
      medicine and Tele-therapy.
AB  - BACKGROUND AND OBJECTIVES: Calculation of 3D dose distribution during
      radiotherapy and nuclear medicine helps us for better treatment of sensitive
      organs such as ovaries and uterus. In this research, we investigate two groups of
      normoxic dosimeters based on meta-acrylic acid (MAGIC and MAGICAUG) and
      polyacrylamide (PAGATUG and PAGATAUG) for brachytherapy, nuclear medicine and
      Tele-therapy in their sensitive and critical role as organ dosimeters. METHODS:
      These polymer gel dosimeters are compared with soft tissue while irradiated by
      different energy photons in therapeutic applications. This comparison has been
      simulated by Monte-Carlo based MCNPX code. ORNL phantom-Female has been used to
      model the critical organs of kidneys, ovaries and uterus. Right kidney is
      proposed to be the source of irradiation and another two organs are exposed to
      this irradiation. RESULTS: Effective atomic numbers of soft tissue, MAGIC,
      MAGICAUG, PAGATUG and PAGATAUG are 6.86, 7.07, 6.95, 7.28, and 7.07 respectively.
      Results show the polymer gel dosimeters are comparable to soft tissue for using
      in nuclear medicine and Tele-therapy. Differences between gel dosimeters and soft
      tissue are defined as the dose responses. This difference is less than 4.1%,
      22.6% and 71.9% for Tele-therapy, nuclear medicine and brachytherapy
      respectively. The results approved that gel dosimeters are the best choice for
      ovaries and uterus in nuclear medicine and Tele-therapy respectively.
      CONCLUSIONS: Due to the slight difference between the effective atomic numbers of
      these polymer gel dosimeters and soft tissue, these polymer gels are not suitable
      for brachytherapy since the dependence of photon interaction to atomic number,
      for low energy brachytherapy, had been so effective. Also this dependence to
      atomic number, decrease for photoelectric and increase for Compton. Therefore
      polymer gel dosimeters are not a good alternative to soft tissue replacement in
      brachytherapy.

PMID- 29650318
TI  - Tissue classification and segmentation of pressure injuries using convolutional
      neural networks.
AB  - BACKGROUND AND OBJECTIVES: This paper presents a new approach for automatic
      tissue classification in pressure injuries. These wounds are localized skin
      damages which need frequent diagnosis and treatment. Therefore, a reliable and
      accurate systems for segmentation and tissue type identification are needed in
      order to achieve better treatment results. METHODS: Our proposed system is based
      on a Convolutional Neural Network (CNN) devoted to performing optimized
      segmentation of the different tissue types present in pressure injuries
      (granulation, slough, and necrotic tissues). A preprocessing step removes the
      flash light and creates a set of 5x5 sub-images which are used as input for the
      CNN network. The network output will classify every sub-image of the validation
      set into one of the three classes studied. RESULTS: The metrics used to evaluate
      our approach show an overall average classification accuracy of 92.01%, an
      average total weighted Dice Similarity Coefficient of 91.38%, and an average
      precision per class of 97.31% for granulation tissue, 96.59% for necrotic tissue,
      and 77.90% for slough tissue. CONCLUSIONS: Our system has been proven to make
      recognition of complicated structures in biomedical images feasible.

PMID- 29650319
TI  - Psoriasis skin biopsy image segmentation using Deep Convolutional Neural Network.
AB  - BACKGROUND AND OBJECTIVE: Development of machine assisted tools for automatic
      analysis of psoriasis skin biopsy image plays an important role in clinical
      assistance. Development of automatic approach for accurate segmentation of
      psoriasis skin biopsy image is the initial prerequisite for developing such
      system. However, the complex cellular structure, presence of imaging artifacts,
      uneven staining variation make the task challenging. This paper presents a
      pioneering attempt for automatic segmentation of psoriasis skin biopsy images.
      METHODS: Several deep neural architectures are tried for segmenting psoriasis
      skin biopsy images. Deep models are used for classifying the super-pixels
      generated by Simple Linear Iterative Clustering (SLIC) and the segmentation
      performance of these architectures is compared with the traditional hand-crafted
      feature based classifiers built on popularly used classifiers like K-Nearest
      Neighbor (KNN), Support Vector Machine (SVM) and Random Forest (RF). A U-shaped
      Fully Convolutional Neural Network (FCN) is also used in an end to end learning
      fashion where input is the original color image and the output is the
      segmentation class map for the skin layers. RESULTS: An annotated real psoriasis
      skin biopsy image data set of ninety (90) images is developed and used for this
      research. The segmentation performance is evaluated with two metrics namely,
      Jaccard's Coefficient (JC) and the Ratio of Correct Pixel Classification (RCPC)
      accuracy. The experimental results show that the CNN based approaches outperform
      the traditional hand-crafted feature based classification approaches.
      CONCLUSIONS: The present research shows that practical system can be developed
      for machine assisted analysis of psoriasis disease.

PMID- 29650320
TI  - Assessment of auditory threshold using Multiple Magnitude-Squared Coherence and
      amplitude modulated tones monaural stimulation around 40 Hz.
AB  - BACKGROUND AND OBJECTIVE: The use of objective detection techniques applied to
      the auditory steady-state responses (ASSRs) for the assessment of auditory
      thresholds has been investigated over the years. The idea consists in setting up
      the audiometric profile without subjective inference from patients and
      evaluators. The challenge encountered is to reduce the detection time of auditory
      thresholds reaching high correlation coefficients between the objective and the
      conventional thresholds, as well as reducing difference between thresholds.
      METHODS: This paper evaluated the use of the Multiple Magnitude-Squared Coherence
      (MMSC) in Auditory Steady-State Responses (ASSRs) evoked by amplitude modulated
      tones around 40 Hz, attaining objective audiograms, which were, later, compared
      to conventional audiograms. It was proposed an analysis of the
      electroencephalogram signals of ten subjects, monaurally stimulated, in the
      intensities 15, 20, 25, 30, 40 and 50 dB SPL, for carrier frequencies of 0.5, 1,
      2 and 4 kHz. After the detection protocol parameters variation, two detectors
      were selected according to behavioral thresholds. RESULTS: The method of this
      study resulted in a Maximum detector with correlation coefficient r = 0.9262,
      mean difference between the objective and behavioral thresholds of 6.44 dB SPL,
      average detection time per ear of 49.96 min and per stimulus of 2.08 min.
      Meanwhile, the Fast detector presented coefficient r = 0.8401, mean difference of
      6.81 dB SPL, average detection time of 28.20 min per ear and 1.18 per stimulus.
      CONCLUSIONS: The results of this study indicate that the MMSC use in the auditory
      responses detection might provide a reliable and efficient estimation of auditory
      thresholds.

PMID- 29650321
TI  - A novel pipeline for adrenal tumour segmentation.
AB  - BACKGROUND AND OBJECTIVE: Adrenal tumours occur on adrenal glands surrounded by
      organs and osteoid. These tumours can be categorized as either functional, non
      functional, malign, or benign. Depending on their appearance in the abdomen,
      adrenal tumours can arise from one adrenal gland (unilateral) or from both
      adrenal glands (bilateral) and can connect with other organs, including the
      liver, spleen, pancreas, etc. This connection phenomenon constitutes the most
      important handicap against adrenal tumour segmentation. Size change, variety of
      shape, diverse location, and low contrast (similar grey values between the
      various tissues) are other disadvantages compounding segmentation difficulty. Few
      studies have considered adrenal tumour segmentation, and no significant
      improvement has been achieved for unilateral, bilateral, adherent, or noncohesive
      tumour segmentation. There is also no recognised segmentation pipeline or method
      for adrenal tumours including different shape, size, or location information.
      METHODS: This study proposes an adrenal tumour segmentation (ATUS) pipeline
      designed to eliminate the above disadvantages for adrenal tumour segmentation.
      ATUS incorporates a number of image methods, including contrast limited adaptive
      histogram equalization, split and merge based on quadtree decomposition, mean
      shift segmentation, large grey level eliminator, and region growing. RESULTS:
      Performance assessment of ATUS was realised on 32 arterial and portal phase
      computed tomography images using six metrics: dice, jaccard, sensitivity,
      specificity, accuracy, and structural similarity index. ATUS achieved remarkable
      segmentation performance, and was not affected by the discussed handicaps, on
      particularly adherence to other organs, with success rates of 83.06%, 71.44%,
      86.44%, 99.66%, 99.43%, and 98.51% for the metrics, respectively, for images
      including sufficient contrast uptake. CONCLUSIONS: The proposed ATUS system
      realises detailed adrenal tumour segmentation, and avoids known disadvantages
      preventing accurate segmentation.

PMID- 29650322
TI  - Decision based on big data research for non-small cell lung cancer in medical
      artificial system in developing country.
AB  - Non-small cell lung cancer (NSCLC) is a high risk cancer and is usually scanned
      by PET-CT for testing, predicting and then give the treatment methods. However,
      in the actual hospital system, at least 640 images must be generated for each
      patient through PET-CT scanning. Especially in developing countries, a huge
      number of patients in NSCLC are attended by doctors. Artificial system can
      predict and make decision rapidly. According to explore and research artificial
      medical system, the selection of artificial observations also can result in low
      work efficiency for doctors. In this study, data information of 2,789,675
      patients in three hospitals in China are collected, compiled, and used as the
      research basis; these data are obtained through image acquisition and diagnostic
      parameter machine decision-making method on the basis of the machine diagnosis
      and medical system design model of adjuvant therapy. By combining image and
      diagnostic parameters, the machine decision diagnosis auxiliary algorithm is
      established. Experimental result shows that the accuracy has reached 77% in
      NSCLC.

PMID- 29650323
TI  - Development and implementation of computational models provides solutions for
      biomedical community.

PMID- 29650324
TI  - Molecular basis of the effect of MMP-9 on the prostate bone metastasis: A review.
AB  - INTRODUCTION AND OBJECTIVE: Prostate cancer (PCa) is the second most common
      cancer in men especially after 50 years old. The metastasis of said cancer
      involves a rise for morbidity, metastasizing 90% of the occasions on bone.
      Metalloproteinases (MMPs) are involved in the process of bone formation and they
      are postulated to be involved in the process of metastasizing, in particular MMP
      9. This work is justified taking into account the scientific interest of the
      subject and the quality of the literature sources used. PCa generates a high
      morbidity and mortality in men, especially due to the process of metastasis,
      resulting in effects to health and socioeconomic level. METHODS: This search was
      performed selecting articles published from 2003 to 2017. Items were selected and
      valued according to the Cochrane criteria (2011). FINDINGS AND CONCLUSIONS: The
      selected articles (17) demonstrate the involvement of MMP-9 as a modulator of
      bone metastatic lesions either of osteoblast, osteoclast or mixed origin as well
      as the recognition of the major mechanisms or molecules involved in the
      regulation of expression gene of MMP-9 and finally establishing the MMP-9 as a
      therapeutic target for possible future drug development. Finally, this study
      evidences MMP-9 as an essential factor for the activation of the chain of the
      different MMPs and consequently in the genesis and development of bone metastasis
      of PCa due to its influence on bone osteoblastic and osteoclastic activity.

PMID- 29650326
TI  - The Plant Target of Rapamycin Kinase: A connecTOR between Sulfur and Growth.
AB  - Sulfur is an essential macronutrient for plants that is incorporated into sulfur
      containing amino acids or metabolites crucial for plant growth and stress
      adaptation. A recent publication shows a connection between sulfur sensing,
      growth processes, and the conserved eukaryotic target of rapamycin (TOR) kinase
      signaling pathway.

PMID- 29650325
TI  - Improving the genetic signature of prostate cancer, the somatic mutations.
AB  - BACKGROUND: Somatic mutations have been related to the highest incidence of
      metastatic disease and different treatment responses. The molecular cause of
      prostate cancer (PC) is still unclear; however, its progression involves
      alterations in oncogenes and tumor suppressor genes as well as somatic mutations
      such as the ones in PIK3CA gene. A high percentage of PC is considered sporadic,
      which means that the damage to the genes occurs by chance after birth (mainly
      somatic mutations will drive the cancer event). However, little is known about
      somatic mutations in PC development. MATERIALS AND METHODS: We evaluated prostate
      biopsies in the main somatic mutations genes (PIK3CA, TP53, EGFR, KIT, KRAS,
      PTEN, and BRAF) among individuals with PSA values>4ng/ml (n = 125), including
      affected and unaffected PC subjects. RESULTS: Mutations in KIT gene are related
      to aggressive PC: TNM stages II to III, Gleason score >= 7 and D'Amico risk (P =
      0.037, 0.040, and 0.017). However, there are no statistical significant results
      when more than 3 somatic mutations are presented in the same individual. In
      relation to environmental factors (smoking, diet, alcohol intake, or workplace
      exposure) there are no significant differences in the effect of environmental
      exposure and the somatic mutation presence. The most prevalent mutations among
      patients with PC are c.1621A>C (rs3822214) in KIT, c.38G>C (rs112445441) in KRAS
      and c.733G>A (rs28934575) in TP53 genes. KRAS, KIT, and TP53 genes are the most
      prevalent ones in patients with PC. CONCLUSIONS: Somatic alterations predisposing
      to chromosomal rearrangements in PC remain largely undefined. We show that KIT,
      KRAS, and TP53 genes have a higher presence among patients with PC and that
      mutations in KIT gene are related to an aggressive PC. However, we did not find
      any environmental effect in somatic mutations among PC individuals.

PMID- 29650327
TI  - Natural selection, plasticity, and the rationale for largest-scale trends.
AB  - Many have argued that there is no reason why natural selection should cause
      directional increases in measures such as body size or complexity across
      evolutionary history as a whole. In this paper I argue that this conclusion does
      not hold for selection for adaptations to environmental variability, and that,
      given the inevitability of environmental variability, trends in adaptations to
      variability are an expected feature of evolution by natural selection. As a
      concrete instance of this causal structure, I outline how this may be applied to
      a trend in phenotypic plasticity.

PMID- 29650328
TI  - [Cardiac manifestations in the acute phase of Kawasaki disease in a third level
      children's hospital in Mexico City].
AB  - OBJECTIVES: To describe the cardiac manifestations in the acute phase of patients
      with Kawasaki disease treated in a third level Children's hospital in Mexico
      City, Mexico. METHODS: A cross-sectional study was conducted in patients with a
      diagnosis of Kawasaki disease treated in this hospital from August 1995 to
      December 2016. Information included patient demographics, clinical features,
      treatment used, electrocardiographic findings, extra-coronary echocardiographic
      findings, and the development of coronary artery aneurysms in the acute phase of
      the disease. RESULTS: The study included 508 cases of Kawasaki disease, with a
      mean age at diagnosis of 37.64+/-35.56 months (range from 2 to 200 months).
      Almost two-thirds (65.4%) of the patients were male, with a male/female ratio of
      1.88:1. Complete Kawasaki disease was diagnosed in 79.2% of cases. Almost all
      cases (92.4%) received intravenous immunoglobulin. Twenty-eight patients (5.5%)
      developed arrhythmias, ST changes developed in 29 patients (5.6%), and 5 patients
      presented with ischaemic changes. In the initial echocardiographic evaluation, 51
      patients (9.9%) were diagnosed with myocarditis, 72 patients (14.0%) with
      pericarditis and 77 cases (15.0%) developed pericardial effusion. Coronary artery
      anomalies were detected in 169 cases (32.9%). 32 cases were diagnosed as giant
      coronary aneurysms. Four patients died from cardiac complications in the acute
      phase of the disease. CONCLUSIONS: There has been an increase in the diagnosis of
      Kawasaki disease in Mexico. They presented with more cardiac complications than
      reported in literature. An increased knowledge of Kawasaki disease is required in
      Mexico in order to establish the cardiac outcomes of this group of patients.

PMID- 29650329
TI  - Perceptions of hospital emergency color codes among hospital employees in Korea.
AB  - INTRODUCTION: Hospital emergency codes frequently comprise of colors to prevent
      confusion and enhance prompt response to emergency situations. The purpose of
      this study was to identify perceptions of emergency color codes among hospital
      employees in Korea. METHODS: A 12-color spectrum and emergency situations were
      selected from the standardized emergency color codes used in the US and Canada.
      Participants were selected via convenience sampling from four general hospitals
      in Seoul and Gyeonggi-Do. Between October 25 and November 30, 2016, 295
      questionnaires were distributed and 266 of them were analyzed. RESULTS: The
      participants showed the highest consistency in the association between emergency
      images related to colors and emergency code color images associated with
      emergency situations in the following cases: "red for fire," "blue for adult
      cardiopulmonary resuscitation (CPR)," "yellow for pediatric CPR," "orange for
      external disaster," "pink for infant/child abduction," "white for deactivation,"
      and "black for violent/combative person." Meanwhile, the most confusing colors
      were purple, gray, and silver. Hospital employees tended to select colors that
      matched the emergency codes used in their respective hospitals. CONCLUSIONS: The
      four colors of "red," "blue," "pink," and "white," were strongly associated with
      "fire," "cardiac arrest," "infant/child abduction," and "emergency deactivation,"
      respectively. The use of four colors for hospital emergency code standardization
      domestically in Korea is recommended.

PMID- 29650330
TI  - Registers in Infant Phonation.
AB  - The primary vocal registers of modal, falsetto, and fry have been studied in
      adults but not per se in infancy. The vocal ligament is thought to play a
      critical role in the modal-falsetto contrast but is still developing during
      infancy (Tateya and Tateya, 2015).41 Cover tissues are also implicated in the
      modal-fry contrast, but the low fundamental frequency (fo) cutoff of 70 Hz,
      shared between genders, suggests a psychoacoustic basis for the contrast. Buder,
      Chorna, Oller, and Robinson (2008)6 used the labels of "loft," "modal," and
      "pulse" for distinct vibratory regimes that appear to be identifiable based on
      spectrographic inspection of harmonic structure and auditory judgments in
      infants, but this work did not supply acoustic measurements to verify which of
      these nominally labeled regimes resembled adult registers. In this report, we
      identify clear transitions between registers within infant vocalizations and
      measure these registers and their transitions for fo and relative harmonic
      amplitudes (H1-H2). By selectively sampling first-year vocalizations, this
      manuscript quantifies acoustic patterns that correspond to vocal fold vibration
      types not previously cataloged in infancy. Results support a developmental basis
      for vocal registers, revealing that a well-developed ligament is not needed for
      loft-modal quality shifts as seen in harmonic amplitude measures. Results also
      reveal that a distinctively pulsatile register can occur in infants at a much
      higher fo than expected on psychoacoustic grounds. Overall results are consistent
      with cover tissues in infancy that are, for vibratory purposes, highly compliant
      and readily detached.

PMID- 29650331
TI  - Spasmodic Dysphonia in Multiple Sclerosis Treatment With Botulin Toxin A: A Pilot
      Study.
AB  - OBJECTIVES: This study aims to evaluate the effect of botulin toxin A in patients
      with multiple sclerosis (MS) affected by spasmodic dysphonia (SD) and to show the
      safety and effectiveness of this treatment in long-term observation. MATERIALS
      AND METHODS: This is a pilot study on three relapsing-remitting MS patients with
      SD and their response to botulin toxin A. RESULTS: None of the patients reported
      dysphagia or other adverse events. Significant improvement was observed in terms
      of both voice quality and laryngostroboscopy results. The treatment effect was
      durable for 6-8 months. CONCLUSIONS: Botulin toxin A is a safe treatment that can
      be successfully used to treat SD in patients with MS. Larger studies are
      necessary to confirm our results.

PMID- 29650332
TI  - Clinicopathological and prognostic significance of MUC13 and AGR2 expression in
      intraductal papillary mucinous neoplasms of the pancreas.
AB  - BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a
      primary pancreatic ductal epithelial neoplasm with the potential to develop into
      an invasive adenocarcinoma. This study aimed to investigate the clinicopathologic
      and prognostic significance of four potential biomarkers for the preoperative
      evaluation of patients with IPMN. MATERIALS AND METHODS: Clinicopathologic
      materials from 104 patients with IPMN who underwent surgical resection at Jichi
      Medical University Hospital were analyzed. IPMNs (110 lesions in total) were
      histologically classified into low-grade IPMN (Group 1; n = 68), high-grade IPMN
      (Group 2; n = 16), or IPMN with an associated invasive carcinoma (Group 3; n =
      26). We evaluated the immunohistochemical expression of MUC13, AGR2, FUT8, and
      FXYD3, which were previously reported to be overexpressed in pancreatic ductal
      adenocarcinoma. RESULTS: The expression of MUC13 was more common in Group 3
      compared with groups 1 and 2 (p < 0.001) and was associated with poor prognosis
      (p = 0.004). The expression of MUC13 was not associated with age, sex, tumor
      location, histological subtype, lymphatic or vascular invasion, or neural
      invasion. In most cases of IPMN, the loss of expression of AGR2 appeared to show
      an association with tumor recurrence and poorly differentiated histology of
      invasive carcinoma; however, this association was not statistically significant.
      The expressions of FUT8 and FXYD3were not associated with the clinicopathological
      features of IPMNs. CONCLUSIONS: The results suggest that MUC13 overexpression and
      loss of expression of AGR2 may predict the progression of IPMN and an unfavorable
      prognosis in patients with IPMN.

PMID- 29650333
TI  - EASL Recommendations on Treatment of Hepatitis C 2018.

PMID- 29650334
TI  - Reply to: "Primed for the spotlight: Transplantation for alcohol-associated liver
      disease".

PMID- 29650335
TI  - A measure of alcohol consumption in late adolescence associated with liver
      disease after 39 years of follow-up is insufficient to guide alcohol safe limits.

PMID- 29650336
TI  - Acute physiological responses to low-intensity blood flow restriction cycling.
AB  - OBJECTIVES: Blood flow restriction (BFR) during interval cycling may stimulate
      aerobic and anaerobic adaptations. However, acute physiological responses to BFR
      interval cycling have not been extensively investigated. DESIGN: Eighteen males
      completed low-intensity (LI), low-intensity with BFR (LIBFR) and high-intensity
      (HI) interval cycling sessions in randomised and counterbalanced order. These
      included a standardised warm-up and three two-min intervals interspersed with two
      min recovery. Interval intensity during HI, LI and LIBFR were 85%, 40% and 40% of
      peak power output obtained during graded exercise tests. METHODS: During LIBFR,
      80% arterial occlusion was applied to both legs during the interval efforts and
      removed during recovery. Continuous measures of heart rate (HR), cardiac output
      (CO) and oxygen consumption (VO2) were recorded. Blood pressure (BP) and rating
      of perceived exertion (RPE) were measured following intervals. Blood lactate
      concentration was measured pre- and post-exercise. RESULTS: BP, HR, CO, VO2,
      lactate and RPE were greatest during HI. During the active intervals, BP, HR and
      CO were greater during LIBFR than LI. VO2 during recovery periods were greater in
      LIBFR than LI. Post-session lactate was greater during LIBFR than LI.
      Importantly, mean arterial pressure during interval three was significantly
      greater in LIBFR (124+/-2mmHg) than HI (114+/-3mmHg). CONCLUSIONS: LIBFR
      increases cardiovascular and metabolic stress compared with LI and could provide
      an alternative aerobic training method for individuals unable to perform high
      intensity exercise. However, increases in mean arterial pressure during LIBFR
      indicates high myocardial workload, and practitioners should therefore use
      caution if prescribing LIBFR for vascular compromised individuals.

PMID- 29650337
TI  - Knee flexion not hip extension strength is persistently reduced following
      hamstring strain injury in Australian Football athletes: Implications for
      Periodic Health Examinations.
AB  - OBJECTIVES: Determine whether clinically feasible tests of isometric lower limb
      strength and range of motion (ROM) in Australian Football (AF) athletes are
      useful in Periodic Health Examinations to identify persistent deficits following
      hamstring strain injury (HSI). DESIGN: Case-control. METHODS: Thirty-seven male,
      semi-professional AF athletes (mean+/-SD; age, 20.2+/-2.9years; height, 1.7+/
      0.5m; mass, 81+/-9.2kg) participated, ten athletes (37%) reported HSI within the
      previous three seasons of competition. Comparisons of pre-season isometric knee
      flexion and hip extension strength variables (peak force, torque and torque
      normalised to body mass) and hip, knee and ankle ROM measures were made between
      athletes with and without past-history of HSI using linear mixed-effect models. A
      logistic regression evaluated whether any of the outcome measures could
      differentiate athletes with a past-history of HSI. RESULTS: Knee flexion peak
      force, torque and torque normalised to body mass were significantly reduced in
      athletes with a past-history of HSI (coefficient, 95% CI) (-44.8N, -86.3 to 
      3.3), (-22.2Nm, -40.5 to -3.7) and (-0.2Nmkg-1, -0.4 to 0.0) respectively. Knee
      flexion peak torque normalised to body mass (Nmkg-1) approached significance as a
      test was able to differentiate athletes with history of HSI (p=0.068). There were
      no differences between groups for any hip extension strength or lower limb ROM
      outcome measures. CONCLUSIONS: Deficits in isometric peak knee flexion strength
      persist for up to three seasons following HSI in AF athletes. Isometric knee
      flexion strength testing may be a clinically feasible option for Periodic Health
      Examinations and inform tertiary injury prevention strategies.

PMID- 29650338
TI  - Comparability of children's sedentary time estimates derived from wrist worn
      GENEActiv and hip worn ActiGraph accelerometer thresholds.
AB  - OBJECTIVES: To examine the comparability of children's free-living sedentary time
      (ST) derived from raw acceleration thresholds for wrist mounted GENEActiv
      accelerometer data, with ST estimated using the waist mounted ActiGraph
      100count.min-1 threshold. DESIGN: Secondary data analysis. METHOD: 108 10-11-year
      old children (n=43 boys) from Liverpool, UK wore one ActiGraph GT3X+ and one
      GENEActiv accelerometer on their right hip and left wrist, respectively for seven
      days. Signal vector magnitude (SVM; mg) was calculated using the ENMO approach
      for GENEActiv data. ST was estimated from hip-worn ActiGraph data, applying the
      widely used 100count.min-1 threshold. ROC analysis using 10-fold hold-out cross
      validation was conducted to establish a wrist-worn GENEActiv threshold comparable
      to the hip ActiGraph 100count.min-1 threshold. GENEActiv data were also
      classified using three empirical wrist thresholds and equivalence testing was
      completed. RESULTS: Analysis indicated that a GENEActiv SVM value of 51mg
      demonstrated fair to moderate agreement (Kappa: 0.32-0.41) with the 100count.min
      1 threshold. However, the generated and empirical thresholds for GENEActiv
      devices were not significantly equivalent to ActiGraph 100count.min-1. GENEActiv
      data classified using the 35.6mg threshold intended for ActiGraph devices
      generated significantly equivalent ST estimates as the ActiGraph 100count.min-1.
      CONCLUSIONS: The newly generated and empirical GENEActiv wrist thresholds do not
      provide equivalent estimates of ST to the ActiGraph 100count.min-1 approach. More
      investigation is required to assess the validity of applying ActiGraph cutpoints
      to GENEActiv data. Future studies are needed to examine the backward
      compatibility of ST data and to produce a robust method of classifying SVM
      derived ST.

PMID- 29650339
TI  - A force profile analysis comparison between functional data analysis, statistical
      parametric mapping and statistical non-parametric mapping in on-water single
      sculling.
AB  - OBJECTIVES: To examine whether the Functional Data Analysis (FDA), Statistical
      Parametric Mapping (SPM) and Statistical non-Parametric Mapping (SnPM) hypothesis
      testing techniques differ in their ability to draw inferences in the context of a
      single, simple experimental design. DESIGN: The sample data used is cross
      sectional (two-sample gender comparison) and evaluation of differences between
      statistical techniques used a combination of descriptive and qualitative
      assessments. METHODS: FDA, SPM and SnPM t-tests were applied to sample data of
      twenty highly skilled male and female rowers, rowing at 32 strokes per minute in
      a single scull boat. Statistical differences for gender were assessed by applying
      two t-tests (one for each side of the boat). RESULTS: The t-statistic values were
      identical for all three methods (with the FDA t-statistic presented as an
      absolute measure). The critical t-statistics (tcrit) were very similar between
      the techniques, with SPM tcrit providing a marginally higher tcrit than the FDA
      and SnPM tcrit values (which were identical). All techniques were successful in
      identifying consistent sections of the force waveform, where male and female
      rowers were shown to differ significantly (p<0.05). CONCLUSIONS: This is the
      first study to show that FDA, SPM and SnPM t-tests provide consistent results
      when applied to sports biomechanics data. Though the results were similar,
      selection of one technique over another by applied researchers and practitioners
      should be based on the underlying parametric assumption of SPM, as well as
      contextual factors related to the type of waveform data to be analysed and the
      experimental research question of interest.

PMID- 29650341
TI  - The relation of Dietary diversity score and food insecurity to metabolic syndrome
      features and glucose level among pre-diabetes subjects.
AB  - INTRODUCTION: Prediabetes is considered as an increased risk factor for
      cardiovascular disease and overt diabetes and is the precursor stage of diabetes.
      Dietary Diversity Score (DDS) is recognized as an essential factor of a high
      quality diet. However, diets with more varieties of food items might increase
      calorie intake and body weight. Therefore, this study was carried out to
      determine the association of DDS with metabolic syndrome features in adults with
      prediabetes. METHODS: Three hundred subjects were randomly selected from
      participants who were undergone diabetes test screening program. Dietary intake
      was assessed by using a validated semi-quantitative food frequency questionnaire.
      DDS was calculated by scoring food intake as nine food groups. The 18-items USDA
      household food securities and International Physical Activity (IPAQ) were also
      measured. The metabolic syndrome was defined according to the Adult Treatment
      Panel III. RESULTS: DDS mean for cases and controls were 4.43 and 4.9,
      respectively (p<0.005). The prevalence of food insecurity was 67/3% in cases and
      55/4% in controls group. The decrease in metabolic syndrome probability was
      compatible with quartiles of DDS (the quartiles odds ratios: 0.6, 0.5, 0.4, 0.19,
      P=0.05). A higher DDS was associated with lower level of fasting blood glucose,
      HDL-cholesterol, TG and Waist circumference. CONCLUSION: Lower DDS was associated
      with high probability of metabolic syndrome and with some features of it, like
      high fasting blood glucose. Therefore, it seems that increase in dietary
      diversity scores could prevent the pre diabetes development to overt diabetes.

PMID- 29650340
TI  - Longitudinal evaluation of efficacy, safety and nutritional status during one
      year treatment with the duodenal-jejunal bypass liner.
AB  - BACKGROUND: The endoscopic duodenal-jejunal bypass liner (DJBL) represents a
      novel temporary endoscopic approach for treatment of obesity-associated type 2
      diabetes. Recent results from the German DJBL registry confirmed substantial
      positive metabolic effects of the DJBL in type 2 diabetes. However, the last Food
      and Drug Administration trial was stopped due to a high occurrence of hepatic
      abscesses (3.5%). OBJECTIVES: Here, we analyzed time courses of development of co
      morbidities, nutritive changes, and occurrence of adverse events during the 1
      year treatment phase with the DJBL in the German DJBL registry. METHODS: Sixty
      six patients from the registry were analyzed for efficacy, safety, and
      nutritional status. Patient data sets were analyzed at implantation, 3 and 6
      months after implantation, and at explantation visits. RESULTS: Weight, body mass
      index, glycated hemoglobin, and low-density lipoprotein cholesterol primarily
      declined during the first 3 months after implantation, whereas systolic and
      diastolic blood pressure were predominantly reduced during the second half of the
      treatment phase. Severe DJBL-associated side effects were mainly documented at
      the explantation visit (intestinal obstruction [1.7%], dislocation [1.7%], and
      liver abscess [1.7%]). Measurements of serum concentrations of ferritin, albumin,
      vitamin B12, folic acid, 25-hydroxyvitamin D3 (25 OH-Vit-D3), and calcium
      provided suggestive evidence of a possible decrease of nutritional absorption of
      vitamins and trace elements by the DJBL. CONCLUSIONS: The DJBL demonstrates high
      efficacy with substantial improvement of all parameters of the metabolic syndrome
      and the potential for reduction of comedications in overweight patients with type
      2 diabetes. These registry results are important to optimize recommendations for
      adaptation of concomitant medication, surveillance of adverse events, nutritional
      status and supplementation, and adaptation of the implantation period of the
      DJBL.

PMID- 29650342
TI  - Aortic valve chordae tendineae causing aortic insufficiency and mimicking an
      aortic root dissection flap.

PMID- 29650343
TI  - Safety, efficacy and Management of subcutaneous treprostinil infusions in the
      treatment of severe pediatric pulmonary hypertension.
AB  - BACKGROUND: Continuous intravenous epoprostenol was the first treatment approved
      for pulmonary arterial hypertension (PAH) but administration through a central
      venous line carries risks of thrombosis and sepsis, particularly in children. We
      sought to evaluate the safety, efficacy and management of subcutaneous (SC)
      treprostinil in children with PAH. METHODS: Fifty-six children (median age 65,
      range 1-200 months) were treated with SC treprostinil. Clinical status,
      echocardiography, NT-proBNP, and site pain and infection were evaluated. Right
      heart catheterization was performed in 54 patients before starting SC
      treprostinil infusion and was repeated at 6 months in 31 patients. RESULTS:
      Treatment was well tolerated in 79% of patients. Site pain resistant to simple
      analgesics occurred in 12 patients (21%), but could be managed in 9/12 children.
      At 6 months, 3 patients had died, 4 had received a Potts shunt and 1 underwent
      lung transplantation. Among the 48 treated patients, 40 (83%) showed significant
      improvement in WHO functional class, 6 minute walk distance, NT-proBNP and
      pulmonary vascular resistance (p < 0.01 for all parameters). At last follow-up
      (median 37 months), ten patients had died, 2 underwent a lung transplantation and
      8 underwent a Potts shunt. In 30 of the 36 remaining treated patients,
      improvement of clinical status was sustained. No children developed sepsis and 12
      had minor site infections. CONCLUSION: Subcutaneous treprostinil infusion is an
      effective therapy without serious side effects in children with PAH. Site pain
      can be managed with simple analgesics in most children.

PMID- 29650344
TI  - Non-invasive testing for sarcopenia predicts future cardiovascular events in
      patients with chronic kidney disease.
AB  - BACKGROUND: Sarcopenia is frequently observed and associated with poor outcomes
      in patients with chronic kidney disease (CKD). A simple screening test for
      sarcopenia using age, grip strength, and calf circumference was recently
      developed. However, the clinical utility of this sarcopenia score in patients
      with CKD remains unclear. METHODS AND RESULTS: We calculated the sarcopenia score
      of 265 patients with CKD and followed the patients for cardiovascular events. The
      endpoint of this study was the composite of cardiovascular hospitalization and
      total mortality. We divided all participants into high (n = 166) and low (n = 99)
      sarcopenia score groups using a simple scoring system. Patients in the high
      sarcopenia score group showed significantly higher plasma B-type natriuretic
      peptide (BNP) levels than those in the low sarcopenia score group (median: 103.1,
      interquartile range: 46.3-310.0 vs. 46.7, 18.0-91.8 pg/mL; p < 0.0001). The
      Kaplan-Meier curve revealed that the risk of cardiovascular events was
      significantly greater in the high sarcopenia score group (log-rank test: p <
      0.0001), even after potential confounding factors were corrected using propensity
      score matching. Multivariate Cox hazard analysis identified a high sarcopenia
      score (hazard ratio: 3.04, 95% confidence interval: 1.45-6.38, p = 0.003) as an
      independent predictor of the primary endpoints. Furthermore, the combination of a
      high sarcopenia score and high BNP level identified patients with a significantly
      higher probability of future events (p < 0.0001). CONCLUSIONS: This study
      demonstrates that this simple screening score for sarcopenia could be a useful
      tool for estimating the future adverse event risk in patients with CKD.

PMID- 29650345
TI  - ?

PMID- 29650346
TI  - Agenesis of the upper lateral incisors: Study of an orthodontic population and
      clinical illustration.
AB  - In his daily practice, the orthodontist is regularly asked to treat patients with
      one or more missing teeth. Considering their functional and esthetic
      specificities, and the relatively high frequency of agenesia, our interest was to
      focus on the permanent lateral upper incisors. Our study, based on an orthodontic
      population including 1000 patients, shows that about 7.8% of these patients
      present agenesis of at least one permanent tooth (out of which 3.6% are agenesis
      of the upper lateral incisor). Treatment options for these cases are multiple
      with several decisional factors to consider: the solutions often lead to
      compromises, and require a multidisciplinary coordination. Therefore, the purpose
      of this article, was to describe the prevalence of these agenesia based on a
      retrospective study, and to present two clinical cases: the first case is a
      bilateral agenesis of the maxillary lateral incisors treated with space opening
      in order to place two implant-supported restorations. The second case is an
      agenesis of tooth 12 treated with space reopening and the placement of a
      cantilever bridge. These clinical cases are presented to illustrate the
      multidisciplinary approach involving orthodontics, prosthodontics, and
      periodontology, in order to achieve the most esthetic and functional results
      possible.

PMID- 29650347
TI  - Risk modeling in prospective diabetes studies: Association and predictive value
      of anthropometrics.
AB  - AIMS: This study aimed to introduce and apply modern statistical techniques for
      assessing association and predictive value of risk factors in first-degree
      relatives (FDR) of patients with diabetes from repeatedly measured diabetes data.
      METHODS: We used data from 1319 FDR's of patients with diabetes followed for 8
      years. Association and predictive performance of weight (Wt), body mass index
      (BMI), waist and hip circumferences (WC and HC) and their ratio (WHR), waist
      height ratio (WHtR) and a body shape index (ABSI) in relation to future diabetes
      were evaluated by using Cox regression and joint longitudinal-survival modeling.
      RESULTS: According to Cox regression, in total sample, WC, HC, Wt, WHtR and BMI
      had significant direct association with diabetes (all p < 0.01) with the best
      predictive ability for WHtR (concordance probability estimate = 0.575). Joint
      modeling suggested direct associations between diabetes and WC, WHR, Wt, WHtR and
      BMI in total sample (all p < 0.05). According to LPML criterion, WHtR was the
      best predictor in both total sample and females with LPML of -2666.27 and 
      2185.67, respectively. However, according to AUC criteria, BMI had the best
      predictive performance with AUC-JM = 0.7629 and dAUC-JM = 0.5883 in total sample.
      In females, both AUC criteria indicated that WC was the best predictor followed
      by WHtR. CONCLUSION: WC, WHR, Wt, WHtR and BMI are among candidate anthropometric
      measures to be monitored in diabetes prevention programs. Larger multi-ethnic and
      multivariate research are warranted to assess interactions and identify the best
      predictors in subgroups.

PMID- 29650348
TI  - The effectiveness of a serious game to enhance empathy for care workers for
      people with disabilities: A parallel randomized controlled trial.
AB  - BACKGROUND: Empathic care is fundamental in healthcare settings and is associated
      to several positive outcomes for care workers (i.e. burnout, compassion
      satisfaction) and patients (i.e. therapeutic alliance, trust, wellbeing). Yet,
      studies showed a decrease in empathy in care workers, which is argued to be a
      product of personal distress. Thus, interventions should aim at enhancing empathy
      in care workers working for vulnerable populations to ensure optimal client-carer
      relationships. OBJECTIVES: The current study investigates the effectiveness of
      the serious game "The world of EMPA" in enhancing empathy in care workers for
      people with disabilities, and tests the effect of personal distress on empathy
      change post intervention. METHODS: We conducted a superiority parallel randomized
      controlled trial (RCT) and tested 224 participants in two conditions: the
      experimental group (n = 111) played a serious game and the control group (n =
      113) read a digital information package about disabilities. Participants were
      assessed on empathy and personal distress prior to and after the intervention.
      RESULTS: Main results showed that the serious game did not significantly enhance
      empathy in care workers, whereas reading a digital information package yield a
      significant decrease in empathy. Exploratory analysis showed that the serious
      game decreased significantly personal distress in care-workers. CONCLUSIONS: This
      study showed that while the serious game "The world of EMPA" did not enhance
      empathy, it resulted in a decrease in personal distress in care workers for
      people with disabilities. Further evidence should corroborate these findings to
      unveil the mechanisms of this intervention and the long-term effects on personal
      distress.

PMID- 29650349
TI  - Perceived influence of intrinsic/extrinsic factors on participation in life
      activities after spinal cord injury.
AB  - BACKGROUND: Various types of limitations on community participation are
      experienced by people with spinal cord injury (SCI). OBJECTIVES: To determine: 1)
      the perceived influence of six intrinsic/extrinsic factors (i.e. physical
      impairment, emotional condition, thinking skills, environment, lack of
      assistance, discrimination) on participation in 26 life activities, 2) if this
      influence varied based on extent of participation, and 3) if personal or
      environmental characteristics influenced perceptions. METHODS: Secondary analysis
      of a cohort (SCI Community Survey, n = 1508) using the SCI Person-Perceived
      Participation in Daily Activities Questionnaire. Frequency tables, Fisher's exact
      tests and correspondence analyses. RESULTS: Respectively, 79.6% and 38.5% of
      respondents perceived that their physical impairment and the natural and/or built
      environment were the main factors that limited participation across all
      activities. Considering participation between three groups (no participation;
      less than wanted; as much as wanted), significant differences (p < 0.001) of
      perceptions were observed in 65% of the combinations (26 activities x 6 factors).
      The hypothesis that respondents who did not participate would perceive the
      highest proportion of limitations was confirmed in 41% of the combinations.
      Perceived influence of the intrinsic/extrinsic factors on participation was not
      significantly influenced by other personal or environmental characteristics.
      CONCLUSION: A majority of people with SCI perceived that their participation is
      limited by one or more of intrinsic/extrinsic factors. Perceptions regarding
      which factors influence participation differ between activities and these
      perceptions appear related to the extent of participation suggesting that those
      who actively participate could be the most sensitive to limitations in certain
      activities.

PMID- 29650351
TI  - Overexpression of ST5, an activator of Ras, has no effect on beta-cell
      proliferation in adult mice.
AB  - OBJECTIVE: Both Type I and Type II diabetes mellitus result from insufficient
      functional beta-cell mass. Efforts to increase beta-cell proliferation as a means
      to restore beta-cell mass have been met with limited success. Suppression of
      Tumorigenicity 5 (ST5) activates Ras/Erk signaling in the presence of Epidermal
      Growth Factor (EGF). In the pancreatic islet, Ras/Erk signaling is required for
      augmented beta-cell proliferation during pregnancy, suggesting that ST5 is an
      appealing candidate to enhance adult beta-cell proliferation. We aimed to test
      the hypothesis that overexpression of ST5 drives adult beta-cell proliferation.
      METHODS: We utilized a doxycycline-inducible bitransgenic mouse model to activate
      beta-cell-specific expression of human ST5 in adult mice at will. Islet
      morphology, beta-cell proliferation, and beta-cell mass in control and ST5
      overexpressing (ST5 OE) animals were analyzed by immunofluorescent staining,
      under basal and two stimulated metabolic states: pregnancy and streptozotocin
      (STZ)-induced beta-cell loss. RESULTS: Doxycycline treatment resulted in robust
      ST5 overexpression in islets from 12-16 week-old ST5 OE animals compared to
      controls, without affecting the islet morphology and identity of the beta-cells.
      Under both basal and metabolically stimulated pregnancy states, beta-cell
      proliferation and mass were comparable in ST5 OE and control animals.
      Furthermore, there was no detectable difference in beta-cell proliferation
      between ST5 OE and control animals in response to STZ-induced beta-cell loss.
      CONCLUSIONS: We successfully derived an inducible bitransgenic mouse model to
      overexpress ST5 specifically in beta-cells. However, our findings demonstrate
      that ST5 overexpression by itself has no mitogenic effect on the adult beta-cell
      under basal and metabolically challenged states.

PMID- 29650352
TI  - Reflections on the "opioid crisis": Prevention is better than cure.

PMID- 29650350
TI  - Loss of dorsomedial hypothalamic GLP-1 signaling reduces BAT thermogenesis and
      increases adiposity.
AB  - OBJECTIVE: Glucagon-like peptide-1 (GLP-1) neurons in the hindbrain densely
      innervate the dorsomedial hypothalamus (DMH), a nucleus strongly implicated in
      body weight regulation and the sympathetic control of brown adipose tissue (BAT)
      thermogenesis. Therefore, DMH GLP-1 receptors (GLP-1R) are well placed to
      regulate energy balance by controlling sympathetic outflow and BAT function.
      METHODS: We investigate this possibility in adult male rats by using direct
      administration of GLP-1 (0.5 ug) into the DMH, knocking down DMH GLP-1R mRNA with
      viral-mediated RNA interference, and by examining the neurochemical phenotype of
      GLP-1R expressing cells in the DMH using in situ hybridization. RESULTS: GLP-1
      administered into the DMH increased BAT thermogenesis and hepatic triglyceride
      (TG) mobilization. On the other hand, Glp1r knockdown (KD) in the DMH increased
      body weight gain and adiposity, with a concomitant reduction in energy
      expenditure (EE), BAT temperature, and uncoupling protein 1 (UCP1) expression.
      Moreover, DMH Glp1r KD induced hepatic steatosis, increased plasma TG, and
      elevated liver specific de-novo lipogenesis, effects that collectively
      contributed to insulin resistance. Interestingly, DMH Glp1r KD increased
      neuropeptide Y (NPY) mRNA expression in the DMH. GLP-1R mRNA in the DMH, however,
      was found in GABAergic not NPY neurons, consistent with a GLP-1R-dependent
      inhibition of NPY neurons that is mediated by local GABAergic neurons. Finally,
      DMH Glp1r KD attenuated the anorexigenic effects of the GLP-1R agonist exendin-4,
      highlighting an important role of DMH GLP-1R signaling in GLP-1-based therapies.
      CONCLUSIONS: Collectively, our data show that DMH GLP-1R signaling plays a key
      role for BAT thermogenesis and adiposity.

PMID- 29650353
TI  - Reprint of: Environmental toxicology and omics: A question of sex.
AB  - : Molecular initiating events and downstream transcriptional/proteomic responses
      provide valuable information for adverse outcome pathways, which can be used
      predict the effects of chemicals on physiological systems. There has been a
      paucity of research that addresses sex-specific expression profiling in
      toxicology and due to cost, time, and logistic considerations, sex as a variable
      has not been widely considered. In response to this deficiency, federal agencies
      in the United States, Canada, and Europe have highlighted the importance of
      including sex as a variable in scientific investigations. Using case studies from
      both aquatic and mammalian toxicology, we report that there can be less than ~20
      25% consensus in how the transcriptome and proteome of each sex responds to
      chemicals. Chemicals that have been shown to elicit sex-specific responses in the
      transcriptome or proteome include pharmaceuticals, anti-fouling agents,
      anticorrosive agents, and fungicides, among others. Sex-specific responses in the
      transcriptome and proteome are not isolated to whole animals, as investigations
      demonstrate that primary cell cultures isolated from each sex responds
      differently to toxicants. This signifies that sex is important, even in cell
      lines. Sex has significant implications for predictive toxicology, and both male
      and female data are required to improve robustness of adverse outcome pathways.
      BIOLOGICAL SIGNIFICANCE: Clinical toxicology recognizes that sex is an important
      variable, as pharmacokinetics (ADME; absorption, distribution, metabolism, and
      excretion) can differ between females and males. However, few studies in
      toxicology have explored the implication of sex in relation to the transcriptome
      and proteome of whole organisms. High-throughput molecular approaches are
      becoming more frequently applied in toxicity screens (e.g. pre-clinical
      experiments, fish embryos, cell lines, synthetic tissues) and such data are
      expected to build upon reporter-based cell assays (e.g. receptor activation,
      enzyme inhibition) used in toxicant screening programs (i.e. Tox21, ToxCast,
      REACH). Thus, computational models can more accurately predict the diversity of
      adverse effects that can occur from chemical exposure within the biological
      system. Our studies and those synthesized from the literature suggest that the
      transcriptome and proteome of females and males respond quite differentially to
      chemicals. This has significant implications for predicting adverse effects in
      one sex when using molecular data generated in the other sex. While molecular
      initiating events are not expected to differ dramatically between females and
      males (i.e. an estrogen binds estrogen receptors in both sexes), it is important
      to acknowledge that the downstream transcriptomic and proteomic responses can
      differ based upon the presence/absence of co-regulators and inherent sex-specific
      variability in regulation of transcriptional and translational machinery.
      Transcriptomic and proteomic studies also reveal that cell processes affected by
      chemicals can differ due to sex, and this can undoubtedly lead to sex-specific
      physiological responses.

PMID- 29650354
TI  - Risk factors for postoperative delirium in patients undergoing free flap
      reconstruction for oral cancer.
AB  - The aim of this study was to investigate risk factors for postoperative delirium
      in patients undergoing free flap reconstruction for defects after oral cancer
      resection. This was a non-randomized, retrospective cohort study involving 102
      patients who underwent oral cancer resection and free flap reconstruction. Data
      were collected from the medical records. Postoperative delirium occurred in 34
      patients (33.3%), of whom 27 were male and seven were female. High preoperative
      total protein and albumin, diabetes mellitus, history of smoking, use of
      hypnotics or antipsychotics, time until getting out of bed after surgery, and
      postoperative insomnia were significantly related to delirium in the univariate
      analysis (P<0.05). In a multiple logistic regression model, high preoperative
      albumin (odds ratio 4.45), postoperative insomnia (odds ratio 10.72), and history
      of smoking (odds ratio 2.91) were significant risk factors for delirium (P<0.05).
      The analysis of laboratory data before and after surgery showed greater decreases
      in albumin, total protein, and haemoglobin after surgery in patients with
      postoperative delirium than in those without this condition. These results show
      that the perioperative maintenance of nutritional status and early postoperative
      management of the sleep cycle are important to prevent delirium after oral cancer
      resection and free flap reconstruction.

PMID- 29650355
TI  - A prospective study examining the effects of treatment timing in the management
      of mandible fractures.
AB  - The ideal timing for treatment of mandible fractures has not been well
      established. The objective of this study was to analyse the effects of treatment
      timing in the surgical management of mandible fractures. A prospective evaluation
      of 215 continuous patients with a total of 359 mandible fractures was undertaken.
      Nine outcome variables were analysed in relation to treatment delay by logistic
      regression modelling: wound dehiscence, hardware exposure, local postoperative
      infection, malocclusion, trismus, nerve damage, fracture non-union, return to
      theatre, and radiographic outcome. Nineteen additional variables were included in
      the analysis to adjust for potential confounding. Delay was measured in days and
      ranged from 0 to 41days, with a mean delay of 4.6days. The incidence of wound
      dehiscence, hardware exposure, local postoperative infection, trismus, nerve
      damage, fracture non-union and return to theatre was 6%, 4%, 11%, 8.5%, 47%, 2%
      and 8%, respectively. Objective malocclusion and poor radiographic outcomes were
      evident in 13% and 4.5% of cases, respectively. No statistically significant
      association was found between treatment delay and treatment outcomes. The
      findings of this study suggest it may be safe to delay the definitive treatment
      of mandible fractures. Treatment delay may allow for improved resource
      distribution and prioritization of more time-dependent interventions.

PMID- 29650356
TI  - Identification of 'Point A' as the prevalent source of error in cephalometric
      analysis of lateral radiographs.
AB  - Deviations in measuring dentofacial components in a lateral X-ray represent a
      major hurdle in the subsequent treatment of dysgnathic patients. In a
      retrospective study, we investigated the most prevalent source of error in the
      following commonly used cephalometric measurements: the angles Sella-Nasion-Point
      A (SNA), Sella-Nasion-Point B (SNB) and Point A-Nasion-Point B (ANB); the Wits
      appraisal; the anteroposterior dysplasia indicator (APDI); and the overbite depth
      indicator (ODI). Preoperative lateral radiographic images of patients with
      dentofacial deformities were collected and the landmarks digitally traced by
      three independent raters. Cephalometric analysis was automatically performed
      based on 1116 tracings. Error analysis identified the x-coordinate of Point A as
      the prevalent source of error in all investigated measurements, except SNB, in
      which it is not incorporated. In SNB, the y-coordinate of Nasion predominated
      error variance. SNB showed lowest inter-rater variation. In addition, our
      observations confirmed previous studies showing that landmark identification
      variance follows characteristic error envelopes in the highest number of tracings
      analysed up to now. Variance orthogonal to defining planes was of relevance,
      while variance parallel to planes was not. Taking these findings into account,
      orthognathic surgeons as well as orthodontists would be able to perform
      cephalometry more accurately and accomplish better therapeutic results.

PMID- 29650357
TI  - Clinical outcomes of Clostridium difficile infection according to strain type. A
      prospective study in medical wards.
AB  - OBJECTIVES: To describe clinical characteristics and outcome of Clostridium
      difficile infection (CDI) patients in Internal Medicine, to identify ribotypes
      (RTs); to evaluate the association between RT and patient clinical
      characteristics and report outcome. METHODS: One year prospective cohort study.
      Clinical data, Barthel Index (BI) and outcomes were collected for all inpatients
      suffering from CDI (n = 148) in hospital wards in Northern Italy. 84 fecal
      samples were analysed for molecular typing. RESULTS: 12 RTs were identified,
      predominantly RT018 (42.9%, n = 36/84) and RT356/607 (40.5%, n = 34/84). Patients
      with dementia were more frequent among those infected by RT018 [55.6% (n = 20/36)
      vs. 32.4% (n = 11/34), p = 0.05]. The median BI score of patients with RT018 was
      lower than BI score of patients with RT356/607 [10 (IQR 0-32) vs. 15 (IQR 5-50),
      p = 0.06]. RT018 infection was associated to higher levels of C-reactive protein
      [7.2 mg/dl (IQR 4.1-14.7) vs. 4.0 mg/dl (IQR 2.2-6.8), p = 0.01] and white blood
      cells >=15,000/dl [33.3% (n = 12/36) vs. 14.7% (n = 5/34) of patients, p = 0.07].
      Higher mortality was noted among RT018 infected patients. We found a continuous
      mortality increase according to the ATLAS score. CONCLUSIONS: Our results confirm
      that RT018 and RT356/607 are the two major RTs causing CDI in older patients with
      a high degree of disability in Northern Italy and RT018 is associated with more
      serious outcomes.

PMID- 29650358
TI  - Prognostic relevance of glomerular filtration rate estimation obtained through
      different equations in hospitalized elderly patients.
AB  - The estimated glomerular filtration rate (eGFR) is a predictor of important
      outcomes and its reduction has been associated with the risk of all-cause
      mortality in both general population and elderly patients. However while reduced
      renal function is common in older people, the best method for estimating GFR
      remains unclear, especially in an acute care setting. Most studies analyzing the
      accuracy of eGFR in the elderly were carried out in different heterogeneous
      settings. In this study, we compare the prognostic value of different formulas
      estimating GFR in predicting the risk of in-hospital morbidity and mortality
      within 3 months from discharge in elderly hospitalized patients. Data were
      extracted from "Registro Politerapia Societa Italiana di Medicina Interna
      (REPOSI)". Patients with available creatinine values at hospital admission were
      selected and eGFR was calculated according to the different formulas: Cockcroft
      Gault, Modification of Diet in Renal Disease equation, Chronic Kidney Disease
      Epidemiology Collaboration, Berlin Initiative Study and Full Age Spectrum. 4621
      patients were included in the analysis. Among these, 4.2% and 14.2% died during
      hospitalization and within 3 months from discharge, respectively. eGFR > 60
      ml/min/1.73 m2 at admission was associated with a very low risk of mortality
      during the hospital stay and within 90 days from discharge, while an eGFR < 60
      ml/min/1.73 m2 was associated with unfavorable outcomes, although with a poor
      level of accuracy (AUC 0.60-0.66). No difference in predictive power between
      different equations was found. Physicians should be aware of the prognostic role
      of eGFR in a comprehensive assessment of elderly in-patients.

PMID- 29650359
TI  - Asymmetric Tyrosination of Spindle Microtubules Facilitates Selfish Inheritance.
AB  - Meiotic drive is an enigmatic process that results from biased segregation of
      selfish genetic elements that enhance their own transmission and drive evolution.
      During asymmetric female meiotic divisions, selfish elements segregate
      preferentially towards the egg rather than polar bodies. Recent findings
      demonstrate that asymmetric spindle tyrosination helps selfish elements to cheat.

PMID- 29650360
TI  - Re: Radiology-led lung escalation pathway: a streamlined innovative service
      expediting the diagnosis of lung cancer. A reply.

PMID- 29650361
TI  - A CRITICal period for chemoradiotherapy in gastric cancer.

PMID- 29650362
TI  - Tazemetostat, an EZH2 inhibitor, in relapsed or refractory B-cell non-Hodgkin
      lymphoma and advanced solid tumours: a first-in-human, open-label, phase 1 study.
AB  - BACKGROUND: Activating enhancer of zeste homolog 2 (EZH2) mutations or
      aberrations of the switch/sucrose non-fermentable (SWI/SNF) complex (eg,
      mutations or deletions of the subunits INI1 or SMARCA4) can lead to aberrant
      histone methylation, oncogenic transformation, and a proliferative dependency on
      EZH2 activity. In this first-in-human study, we aimed to investigate the safety,
      clinical activity, pharmacokinetics, and pharmacodynamics of tazemetostat, a
      first-in-class selective inhibitor of EZH2. METHODS: We did an open-label,
      multicentre, dose-escalation, phase 1 study using a 3 + 3 design with planned
      cohort expansion at the two highest doses below the maximally tolerated dose. The
      study was done at two centres in France: Institut Gustave Roussy (Villejuif, Val
      de Marne) and Institut Bergonie (Bordeaux, Gironde). Eligible patients had
      relapsed or refractory B-cell non-Hodgkin lymphoma or an advanced solid tumour
      and were older than 18 years, with Eastern Cooperative Oncology Group performance
      status of 0 or 1, and adequate end-organ function. Tazemetostat was administered
      orally from 100 mg twice daily to 1600 mg twice daily in 28-day cycles. The
      primary endpoint was to establish the maximum tolerated dose or recommended phase
      2 dose of tazemetostat, as determined by dose-limiting toxicities, laboratory
      values, and other safety or pharmacokinetic measures in cycle one according to
      local investigator assessment. Safety was assessed in patients who received at
      least one dose of tazemetostat; antitumour activity was assessed in the intention
      to-treat population. This study is registered with ClinicalTrials.gov, number
      NCT01897571. The phase 1 part of the study is complete, and phase 2 is ongoing.
      FINDINGS: Between June 13, 2013, and Sept 21, 2016, 64 patients (21 with B-cell
      non-Hodgkin lymphoma, and 43 with advanced solid tumours) received doses of
      tazemetostat. The most common treatment-related adverse events, regardless of
      attribution, were asthenia (21 [33%] of 64 treatment-related events), anaemia
      (nine [14%]), anorexia (four [6%]), muscle spasms (nine [14%]), nausea (13
      [20%]), and vomiting (six [9%]), usually grade 1 or 2 in severity. A single dose
      limiting toxicity of grade 4 thrombocytopenia was identified at the highest dose
      of 1600 mg twice daily. No treatment-related deaths occurred; seven (11%)
      patients had non-treatment-related deaths (one at 200 mg twice daily, four at 400
      mg twice daily, and two at 1600 mg twice daily). The recommended phase 2 dose was
      determined to be 800 mg twice daily. Durable objective responses, including
      complete responses, were observed in eight (38%) of 21 patients with B-cell non
      Hodgkin lymphoma and two (5%) of 43 patients with solid tumours. INTERPRETATION:
      Tazemetostat showed a favourable safety profile and antitumour activity in
      patients with refractory B-cell non-Hodgkin lymphoma and advanced solid tumours,
      including epithelioid sarcoma. Further clinical investigation of tazemetostat
      monotherapy is ongoing in phase 2 studies in adults and a phase 1 study for
      children, which are currently enrolling patients who have B-cell non-Hodgkin
      lymphoma and INI1-negative or SMARCA4-negative tumours. FUNDING: Epizyme and
      Eisai.

PMID- 29650364
TI  - Targeting EZH2 with tazemetostat.

PMID- 29650363
TI  - Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy
      for resectable gastric cancer (CRITICS): an international, open-label, randomised
      phase 3 trial.
AB  - BACKGROUND: Both perioperative chemotherapy and postoperative chemoradiotherapy
      improve survival in patients with resectable gastric cancer from Europe and North
      America. To our knowledge, these treatment strategies have not been investigated
      in a head to head comparison. We aimed to compare perioperative chemotherapy with
      preoperative chemotherapy and postoperative chemoradiotherapy in patients with
      resectable gastric adenocarcinoma. METHODS: In this investigator-initiated, open
      label, randomised phase 3 trial, we enrolled patients aged 18 years or older who
      had stage IB- IVA resectable gastric or gastro-oesophageal adenocarcinoma (as
      defined by the American Joint Committee on Cancer, sixth edition), with a WHO
      performance status of 0 or 1, and adequate cardiac, bone marrow, liver, and
      kidney function. Patients were enrolled from 56 hospitals in the Netherlands,
      Sweden, and Denmark, and were randomly assigned (1:1) with a computerised
      minimisation programme with a random element to either perioperative chemotherapy
      (chemotherapy group) or preoperative chemotherapy with postoperative
      chemoradiotherapy (chemoradiotherapy group). Randomisation was done before
      patients were given any preoperative chemotherapy treatment and was stratified by
      histological subtype, tumour localisation, and hospital. Patients and
      investigators were not masked to treatment allocation. Surgery consisted of a
      radical resection of the primary tumour and at least a D1+ lymph node dissection.
      Postoperative treatment started within 4-12 weeks after surgery. Chemotherapy
      consisted of three preoperative 21-day cycles and three postoperative cycles of
      intravenous epirubicin (50 mg/m2 on day 1), cisplatin (60 mg/m2 on day 1) or
      oxaliplatin (130 mg/m2 on day 1), and capecitabine (1000 mg/m2 orally as tablets
      twice daily for 14 days in combination with epirubicin and cisplatin, or 625
      mg/m2 orally as tablets twice daily for 21 days in combination with epirubicin
      and oxaliplatin), received once every three weeks. Chemoradiotherapy consisted of
      45 Gy in 25 fractions of 1.8 Gy, for 5 weeks, five daily fractions per week,
      combined with capecitabine (575 mg/m2 orally twice daily on radiotherapy days)
      and cisplatin (20 mg/m2 intravenously on day 1 of each 5 weeks of radiation
      treatment). The primary endpoint was overall survival, analysed by intention-to
      treat. The CRITICS trial is registered at ClinicalTrials.gov, number NCT00407186;
      EudraCT, number 2006-004130-32; and CKTO, 2006-02. FINDINGS: Between Jan 11,
      2007, and April 17, 2015, 788 patients were enrolled and randomly assigned to
      chemotherapy (n=393) or chemoradiotherapy (n=395). After preoperative
      chemotherapy, 372 (95%) of 393 patients in the chemotherapy group and 369 (93%)
      of 395 patients in the chemoradiotherapy group proceeded to surgery, with a
      potentially curative resection done in 310 (79%) of 393 patients in the
      chemotherapy group and 326 (83%) of 395 in the chemoradiotherapy group.
      Postoperatively, 233 (59%) of 393 patients started chemotherapy and 245 (62%) of
      395 started chemoradiotherapy. At a median follow-up of 61.4 months (IQR 43.3
      82.8), median overall survival was 43 months (95% CI 31-57) in the chemotherapy
      group and 37 months (30-48) in the chemoradiotherapy group (hazard ratio from
      stratified analysis 1.01 (95% CI 0.84-1.22; p=0.90). After preoperative
      chemotherapy, in the total safety population of 781 patients (assessed together),
      there were 368 (47%) grade 3 adverse events; 130 (17%) grade 4 adverse events,
      and 13 (2%) deaths. Causes of death during preoperative treatment were diarrhoea
      (n=2), dihydropyrimidine deficiency (n=1), sudden death (n=1), cardiovascular
      events (n=8), and functional bowel obstruction (n=1). During postoperative
      treatment, grade 3 and 4 adverse events occurred in 113 (48%) and 22 (9%) of 233
      patients in the chemotherapy group, respectively, and in 101 (41%) and ten (4%)
      of 245 patients in the chemoradiotherapy group, respectively. Non-febrile
      neutropenia occurred more frequently during postoperative chemotherapy (79 [34%]
      of 233) than during postoperative chemoradiotherapy (11 [4%] of 245). No deaths
      were observed during postoperative treatment. INTERPRETATION: Postoperative
      chemoradiotherapy did not improve overall survival compared with postoperative
      chemotherapy in patients with resectable gastric cancer treated with adequate
      preoperative chemotherapy and surgery. In view of the poor postoperative patient
      compliance in both treatment groups, future studies should focus on optimising
      preoperative treatment strategies. FUNDING: Dutch Cancer Society, Dutch
      Colorectal Cancer Group, and Hoffmann-La Roche.

PMID- 29650365
TI  - Expression of the human UDP-galactose transporter gene hUGT1 in tobacco plants'
      enhanced plant hardness.
AB  - We reported previously that tobacco plants transformed with the human UDP
      galactose transporter 1 gene (hUGT1) had enhanced growth, displayed
      characteristic traits, and had an increased proportion of galactose (hyper
      galactosylation) in the cell wall matrix polysaccharides. Here, we report that
      hUGT1-transgenic plants have an enhanced hardness. As determined by breaking and
      bending tests, the leaves and stems of hUGT1-transgenic plants were harder than
      those of control plants. Transmission electron microscopy revealed that the cell
      walls of palisade cells in leaves, and those of cortex cells and xylem fibers in
      stems of hUGT1-transgenic plants, were thicker than those of control plants. The
      increased amounts of total cell wall materials extracted from the leaves and
      stems of hUGT1-transgenic plants supported the increased cell wall thickness. In
      addition, the cell walls of the hUGT1-transgenic plants showed an increased
      lignin contents, which was supported by the up-regulation of lignin biosynthetic
      genes. Thus, the heterologous expression of hUGT1 enhanced the accumulation of
      cell wall materials, which was accompanied by the increased lignin content,
      resulting in the increased hardness of the leaves and stems of hUGT1-trangenic
      plants. The enhanced accumulation of cell wall materials might be related to the
      hyper-galactosylation of cell wall matrix polysaccharides, most notably
      arabinogalactan, because of the enhanced UDP-galactose transport from the cytosol
      to the Golgi apparatus by hUGT1, as suggested in our previous report.

PMID- 29650366
TI  - Mannose Receptor and the Mystery of Nonhealing Leishmania major Infection.
AB  - Scientists have long puzzled over the ability of Leishmania major Seidman (LmSd)
      to form nonhealing cutaneous lesions in the face of a strong Th1 response. A
      recent study identified a population of dermal macrophages that are
      preferentially infected by LmSd in a mannose receptor 1-, C-type 1 (MRC1/CD206)
      dependent manner.

PMID- 29650367
TI  - Reply to the letter to the editor YMATH_2018_15:"Two-point discrimination and the
      low back pain: Not as unreliable as it seems, but what about standardised
      procedures?" regarding our article MSKSP_168:"A systematic review and meta
      analysis of the reliability and validity of sensorimotor measurement instruments
      in people with chronic low back pain".

PMID- 29650368
TI  - Protein Corona in Response to Flow: Effect on Protein Concentration and
      Structure.
AB  - Nanoparticles used in cellular applications encounter free serum proteins that
      adsorb onto the surface of the nanoparticle, forming a protein corona. This
      protein layer controls the interaction of nanoparticles with cells. For
      nanomedicine applications, it is important to consider how intravenous injection
      and the subsequent shear flow will affect the protein corona. Our goal was to
      determine if shear flow changed the composition of the protein corona and if
      these changes affected cellular binding. Colorimetric assays of protein
      concentration and gel electrophoresis demonstrate that polystyrene nanoparticles
      subjected to flow have a greater concentration of serum proteins adsorbed on the
      surface, especially plasminogen. Plasminogen, in the absence of nanoparticles,
      undergoes changes in structure in response to flow, characterized by fluorescence
      and circular dichroism spectroscopy. The protein-nanoparticle complexes formed
      from fetal bovine serum after flow had decreased cellular binding, as measured
      with flow cytometry. In addition to the relevance for nanomedicine, these results
      also highlight the technical challenges of protein corona studies. The
      composition of the protein corona was highly dependent on the initial mixing
      step: rocking, vortexing, or flow. Overall, these results reaffirm the importance
      of the protein corona in nanoparticle-cell interactions and point toward the
      challenges of predicting corona composition based on nanoparticle properties.

PMID- 29650369
TI  - SPT and Imaging FCS Provide Complementary Information on the Dynamics of Plasma
      Membrane Molecules.
AB  - The dynamics of biomolecules in the plasma membrane is of fundamental importance
      to understanding cellular processes. Cellular signaling often starts with
      extracellular ligand binding to a membrane receptor, which then transduces an
      intracellular signal. Ligand binding and receptor-complex activation often
      involve a complex rearrangement of proteins in the membrane, which results in
      changes in diffusion properties. Two widely used methods to characterize
      biomolecular diffusion are single-particle tracking (SPT) and imaging total
      internal reflection fluorescence correlation spectroscopy (ITIR-FCS). Here, we
      compare the results of recovered diffusion coefficients and mean-square
      displacements of the two methods by simulations of free, domain-confined, or
      meshwork diffusion. We introduce, to our knowledge, a new method for the
      determination of confinement radii from ITIR-FCS data. We further establish and
      demonstrate simultaneous SPT/ITIR-FCS for direct comparison within living cells.
      Finally, we compare the results obtained by SPT and ITIR-FCS for the receptor
      tyrosine kinase MET. Our results show that SPT and ITIR-FCS yield complementary
      information on diffusion properties of biomolecules in cell membranes.

PMID- 29650370
TI  - Open-Boundary Molecular Dynamics of a DNA Molecule in a Hybrid Explicit/Implicit
      Salt Solution.
AB  - The composition and electrolyte concentration of the aqueous bathing environment
      have important consequences for many biological processes and can profoundly
      affect the behavior of biomolecules. Nevertheless, because of computational
      limitations, many molecular simulations of biophysical systems can be performed
      only at specific ionic conditions: either at nominally zero salt concentration,
      i.e., including only counterions enforcing the system's electroneutrality, or at
      excessive salt concentrations. Here, we introduce an efficient molecular dynamics
      simulation approach for an atomistic DNA molecule at realistic physiological
      ionic conditions. The simulations are performed by employing the open-boundary
      molecular dynamics method that allows for simulation of open systems that can
      exchange mass and linear momentum with the environment. In our open-boundary
      molecular dynamics approach, the computational burden is drastically alleviated
      by embedding the DNA molecule in a mixed explicit/implicit salt-bathing solution.
      In the explicit domain, the water molecules and ions are both overtly present in
      the system, whereas in the implicit water domain, only the ions are explicitly
      present and the water is described as a continuous dielectric medium. Water
      molecules are inserted and deleted into/from the system in the intermediate
      buffer domain that acts as a water reservoir to the explicit domain, with both
      water molecules and ions free to enter or leave the explicit domain. Our approach
      is general and allows for efficient molecular simulations of biomolecules
      solvated in bathing salt solutions at any ionic strength condition.

PMID- 29650371
TI  - Turo (Qi Dance) Program for Parkinson's Disease Patients: Randomized, Assessor
      Blind, Waiting-List Control, Partial Crossover Study.
AB  - CONTEXT: Qigong, Tai-chi and dancing have all been proven effective for
      Parkinson's disease (PD); however, no study has yet assessed the efficacy of
      Turo, a hybrid qigong dancing program developed to relieve symptoms in PD
      patients. OBJECTIVE: To determine whether Turo may provide benefit in addressing
      the symptoms of PD patients. DESIGN: Randomized, assessor blind, waiting-list
      control, partial crossover study. SETTING: Kyung Hee University Korean Medicine
      Hospital, Seoul, Republic of Korea. PARTICIPANTS: A total of 32 PD patients (mean
      age 65.7 +/- 6.8). INTERVENTION: Participants were assigned to the Turo group or
      the waiting-list control group. The Turo group participated in an 8-week Turo
      training program (60-minute sessions twice a week). The waiting-list control
      group received no additional treatment during the same period; then underwent the
      same 8-week Turo training. OUTCOME MEASURES: The primary outcome was a score on
      the Unified Parkinson's Disease Rating Scale (UPDRS), and the secondary outcomes
      included the perceived health status assessed using the Parkinson's disease
      Quality of Life questionnaire (PDQL), balance function as assessed by the Berg
      Balance Scale (BBS) and the results of the Beck Depression Inventory (BDI).
      RESULTS: The Turo group showed statistically significant improvements in the
      UPDRS (P < 0.01) and PDQL (P < 0.05) as compared to the control group. The
      changes in BBS scores displayed a tendency toward improvement, but was not
      statistically significant (P = 0.051). CONCLUSION: These findings suggest that
      Turo PD training might improve the symptoms of PD patients.

PMID- 29650372
TI  - Genomic signatures of parasite-driven natural selection in north European
      Atlantic salmon (Salmo salar).
AB  - Understanding the genomic basis of host-parasite adaptation is important for
      predicting the long-term viability of species and developing successful
      management practices. However, in wild populations, identifying specific
      signatures of parasite-driven selection often presents a challenge, as it is
      difficult to unravel the molecular signatures of selection driven by different,
      but correlated, environmental factors. Furthermore, separating parasite-mediated
      selection from similar signatures due to genetic drift and population history can
      also be difficult. Populations of Atlantic salmon (Salmo salar L.) from northern
      Europe have pronounced differences in their reactions to the parasitic flatworm
      Gyrodactylus salaris Malmberg 1957 and are therefore a good model to search for
      specific genomic regions underlying inter-population differences in pathogen
      response. We used a dense Atlantic salmon SNP array, along with extensive
      sampling of 43 salmon populations representing the two G. salaris response
      extremes (extreme susceptibility vs resistant), to screen the salmon genome for
      signatures of directional selection while attempting to separate the parasite
      effect from other factors. After combining the results from two independent
      genome scan analyses, 57 candidate genes potentially under positive selection
      were identified, out of which 50 were functionally annotated. This candidate gene
      set was shown to be functionally enriched for lymph node development, focal
      adhesion genes and anti-viral response, which suggests that the regulation of
      both innate and acquired immunity might be an important mechanism for salmon
      response to G. salaris. Overall, our results offer insights into the apparently
      complex genetic basis of pathogen susceptibility in salmon and highlight
      methodological challenges for separating the effects of various environmental
      factors.

PMID- 29650373
TI  - Repair of post-laryngectomy pharyngocutaneous fistulas using a pectoralis major
      flap.
AB  - INTRODUCTION: The pectoralis major flap is a reconstructive option to consider in
      the treatment of pharyngocutaneous fistula after a total laryngectomy. There are
      not large studies assessing variables related to pharyngocutaneous fistula
      recurrence after removal of the larynx. Our objectives were to review the results
      obtained with this type of treatment when pharyngocutaneous fistula appears in
      laryngectomized patients, and to evaluate variables related to the results.
      METHODS: We retrospectively reviewed our results using either a myocutaneous or
      fasciomuscular pectoralis major flap to repair pharyngocutaneous fistula in 50
      patients. RESULTS: There were no cases of flap necrosis. Oral intake after
      fistula repair with a pectoralis major flap was restored in 94% of cases. Fistula
      recurrence occurred in 22 cases (44%), and it was associated with a lengthening
      of the hospital stay. Performing the flap as an emergency procedure was
      associated with a significantly higher risk of fistula recurrence. Hospital stay
      was significantly shorter when a salivary tube was placed. CONCLUSIONS: The
      pectoralis major flap is a useful approach to repair pharyngocutaneous fistula.
      Placing salivary tubes during fistula repair significantly reduces hospital stay
      and complication severity in case of pharyngocutaneous fistula recurrence.

PMID- 29650374
TI  - Hoarseness and vocal tract discomfort and associated risk factors in air traffic
      controllers.
AB  - INTRODUCTION: An air traffic controller is a professional who performs air
      traffic control functions in air traffic control units and is responsible for
      controlling the various stages of a flight. OBJECTIVE: To compare hoarseness and
      vocal tract discomfort and their risk factors among air traffic controllers in
      the approach control of Sao Paulo. METHODS: In a cross-sectional survey, a voice
      self-evaluation adapted from to self-evaluation prepared by the Brazilian
      Ministry of Labor for teachers was administered to 76 air traffic controllers at
      approach control of Sao Paulo, Brazil. RESULTS: The percentage of hoarseness and
      vocal tract discomfort was 19.7% and 38.2%, respectively. In relation to air
      pollution, the percentages of hoarseness and vocal tract discomfort were higher
      among those who consider their working environment to be intolerable than among
      those in a comfortable or disturbing environment. The percentage of hoarseness
      was higher among those who seek medical advice due to vocal complaints and among
      those who experience difficulty using their voice at work than among those who
      experience mild or no difficulty. The percentage of vocal tract discomfort was
      higher among those in a very tense and stressful environment than among those who
      consider their work environment to be mild or moderately tense and stressful. The
      percentage of vocal tract discomfort was higher among those who describe
      themselves as very tense and stressed or tense and stressed than among those who
      describe themselves as calm. Additionally, the percentage of vocal tract
      discomfort was higher among those who care about their health. CONCLUSION: Among
      air traffic controllers, the percentage of vocal tract discomfort was almost
      twice that of hoarseness. Both symptoms are prevalent among air traffic
      controllers who considered their workplace intolerable in terms of air pollution.
      Vocal tract discomfort was related to a tense and stressful environment, and
      hoarseness was related to difficulty using the voice at work.

PMID- 29650375
TI  - Vascularized Distal Radius Bone Graft for Treatment of Ulnar Nonunion.
AB  - Various methods have been reported to treat forearm nonunions with good results.
      However, in the presence of infection, inadequate vascularity of surrounding
      tissues, or failed prior grafts, vascularized bone grafts are a valid
      alternative. We describe the surgical technique to obtain distal radius
      vascularized bone graft pedicled on the radial artery (RA) and its clinical
      application in 1 case of an ulnar nonunion. We studied the surgical technique in
      12 freshly injected cadavers. In the distal forearm, the RA provides several
      periosteal branches to supply the distal radius metaphysis. These vessels are
      located between the distal insertion of the brachioradialis and the deep surface
      of the radial half of the pronator quadratus. A 6-cm vascularized bone graft can
      be harvested from the radius, and dissection of the RA enables a long pedicle
      with a wide arc of rotation readily able to reach the proximal part of the ulna.
      The present technique is a reproducible alternative that allows the treatment of
      bone defects up to 6 cm, without the potential technical difficulties of a free
      bone flap.

PMID- 29650376
TI  - Trapezius Muscle Transfer for Restoration of Elbow Extension in a Traumatic
      Brachial Plexus Injury.
AB  - Voluntary elbow extension is essential for optimal upper limb positioning
      required for daily living activities, particularly above-shoulder maneuvers. The
      authors present a case of traumatic brachial plexus injury in which paralysis of
      the musculature selectively supplied by the posterior cord was based on magnetic
      resonance imaging and nerve conduction studies. An attempt at a radial nerve
      graft at another center was not effective. Ipsilateral hand function improved
      after multiple local tendon transfers were performed. Restoration of active elbow
      extension was not possible using the posterior deltoid or the latissimus dorsi
      because they were denervated by the primary trauma and so the trapezius muscle
      was used as a donor muscle unit to restore voluntary elbow extension. The patient
      resumed biking 6 weeks after the transfer procedure. At 2-year follow-up, full
      active elbow extension was regained, elbow extension power scored 4 of 5, and the
      patient reported that he could ride his bicycle for 70 miles.

PMID- 29650377
TI  - Articular Surgery of the Ischemic Hand in Systemic Scleroderma: A Vascular Basis
      for Arthrodesis and Arthroplasty.
AB  - Hallmark deformities of systemic scleroderma are early onset and progressively
      disabling flexion contractures of the proximal interphalangeal (PIP) joints often
      in conjunction with extension or, less frequently, flexion contractures of the
      metacarpophalangeal (MCP) joints. Although surgical correction is generally
      recommended, a prevailing reluctance for operative treatment exists owing to the
      inherent ischemia of the disease with its potentially compromised healing
      capacity. Nonetheless, with recognition and preservation of the tenuous but well
      defined and constant periarticular vascular networks of the PIP and MCP joints,
      articular reconstruction with uncomplicated wound healing can prove consistently
      successful for patients with scleroderma. This article describes the authors'
      preferred methods of PIP arthrodesis vascularized by the dorsal cutaneous
      arterial network and MCP silicone implant arthroplasty perfused by the dorsal
      metacarpal arterial plexus.

PMID- 29650378
TI  - Long-Term Clinical Outcome After Titanium Lunate Arthroplasty for Kienbock
      Disease.
AB  - PURPOSE: Titanium lunate arthroplasty (TLA) for Kienbock disease was introduced
      in 1984 to address the silicone-wear particle problem common to silicone lunate
      implants. We sought to study the outcome of TLA. METHODS: We identified 11
      patients from our hospital database who had undergone TLA between 2001 and 2010.
      We evaluated pain, range of motion (ROM), function, and radiological outcome at a
      mean 11 years after surgery. We compared preoperative ROM and radiological
      findings with final follow-up in the ipsilateral wrist and also made comparisons
      with the contralateral wrists. RESULTS: No implants were removed, and no wrist
      joints were fused. Pain on the visual analog scale averaged 0.5 at rest, 0.3 at
      night, and 2.7 during heavy exertion. Seven patients had no pain at rest and 9
      had no pain at night. Range of motion reached 70% of that of the contralateral
      wrist, and strength reached 81%. The Disabilities of the Arm, Shoulder, and Hand
      (DASH) score averaged 9.6, optional DASH 9.7, and Mayo wrist score 67.7.
      Radiologically, only Stahl and arthrosis indexes differed significantly between
      affected and unaffected wrists. Two patients had a dorsally dislocated implant,
      meaning that around 20% of our cases probably meet the criteria for failure.
      CONCLUSIONS: The longer-term results of TLA for stage III Kienbock disease are
      promising. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 29650379
TI  - ?
AB  - The reactive solute transport in a single fracture bounded by upper and lower
      matrixes is a classical problem that captures the dominant factors affecting
      transport behavior beyond pore scale. A parallel fracture-matrix system which
      considers the interaction among multiple paralleled fractures is an extension to
      a single fracture-matrix system. The existing analytical or semi-analytical
      solution for solute transport in a parallel fracture-matrix simplifies the
      problem to various degrees, such as neglecting the transverse dispersion in the
      fracture and/or the longitudinal diffusion in the matrix. The difficulty of
      solving the full two-dimensional (2-D) problem lies in the calculation of the
      mass exchange between the fracture and matrix. In this study, we propose an
      innovative Green's function approach to address the 2-D reactive solute transport
      in a parallel fracture-matrix system. The flux at the interface is calculated
      numerically. It is found that the transverse dispersion in the fracture can be
      safely neglected due to the small scale of fracture aperture. However, neglecting
      the longitudinal matrix diffusion would overestimate the concentration profile
      near the solute entrance face and underestimate the concentration profile at the
      far side. The error caused by neglecting the longitudinal matrix diffusion
      decreases with increasing Peclet number. The longitudinal matrix diffusion does
      not have obvious influence on the concentration profile in long-term. The
      developed model is applied to a non-aqueous-phase-liquid (DNAPL) contamination
      field case in New Haven Arkose of Connecticut in USA to estimate the
      Trichloroethylene (TCE) behavior over 40 years. The ratio of TCE mass stored in
      the matrix and the injected TCE mass increases above 90% in less than 10 years.

PMID- 29650380
TI  - Assessment of Temporomandibular Joint Dysfunction in Patients with Stroke.
AB  - GOAL: The aim of this study was to assess temporomandibular joint dysfunction in
      patients with stroke. MATERIALS AND METHODS: Total of 100 participants, 50
      healthy and 50 who had stroke, were recruited into this study. Digital caliper
      and algometer were used to assess temporomandibular joint range of motion and
      masticatory muscle pressure pain threshold. Labial commissure angle measurement
      was used for the assessment of facial paralysis severity. Fonseca questionnaire
      was used for temporomandibular joint dysfunction assessment and categorization.
      In addition, dominant mastication shift was measured by the question that asks
      the pre and poststroke dominant mastication side. FINDINGS: In intergroup
      comparison, significant decrease was found in all temporomandibular range of
      motion parameters in favor of stroke group (P < .05). Despite the fact that no
      significant difference was found between groups for the pain threshold in
      masticatory muscles except for middle part of the left temporalis muscle, values
      were higher in healthy group (P > .05). As a result of intergroup examination of
      labial commissure angle degree, Fonseca questionnaire score, it was found that
      labial commissure angle and Fonseca questionnaire scores were higher in stroke
      group (P < .05). Intragroup examination of patients with stroke showed that
      dominant mastication side shift was seen in patients with stroke (P < .05).
      CONCLUSION: It was concluded that, temporomandibular joint dysfunction prevalence
      was higher in stroke group compared with healthy group and use of modalities
      specific to temporomandibular joint dysfunction treatment would be beneficial.

PMID- 29650381
TI  - Is the Population Detected by Screening in China Truly at High Risk of Stroke?
AB  - AIM: The Chinese Stroke Screening and Prevention Project (CSSPP) considers
      patients with 3 or more risk factors to be at high risk of stroke, and does not
      quantitatively assess the risk for stroke. However, to detect high-risk groups
      more efficiently, a health risk appraisal (HRA) model should be used to assess
      individual risk of stroke. METHODS: The odds ratios for the 8 risk factors for
      stroke were pooled and the data were used to develop an HRA model to predict
      individuals' risks of developing stroke in the next 5 years. The Chinese
      screening project and HRA screening strategies were then compared. RESULTS: We
      assessed 4196 Chinese individuals who received checkups in 2015. The average 5
      year risk of stroke was 5.810/00, with men being at higher risk of stroke than
      women over that period. The average 5-year risk of stroke also increased with the
      number of risk factors. 932 individuals (22.2%) were identified as being at high
      risk of stroke according to CSSPP, whereas 318 individuals with fewer than 3 risk
      factors were considered being at low risk despite having a 5-year risk of stroke
      greater than 4.0% by our assessment. Notably, among patients with hypertension
      and diabetes who were classified as being at low risk of stroke by the CSSPP, the
      HRA recognized 15.9% and 14.3% as being at high risk of stroke, respectively.
      CONCLUSION: All 8 major risk factors affect stroke risk differently, and the
      efficiency of clustering these risk factors might be improved by considering the
      relative risk of each factor with an HRA model.

PMID- 29650382
TI  - Therapeutic Decisions in Atrial Fibrillation for Stroke Prevention: The Role of
      Aversion to Ambiguity and Physicians' Risk Preferences.
AB  - BACKGROUND: Knowledge-to-action gaps influence therapeutic decisions in atrial
      fibrillation (AF). Physician-related factors are common, but the least studied.
      We evaluated the prevalence and determinants of physician-related factors and
      knowledge-to-action gaps among physicians involved in the management of AF
      patients. DESIGN: In this cross-sectional study, participants from 6 South
      American countries recruited during an educational program answered questions
      regarding 16 case scenarios of patients with AF and completed experiments
      assessing 3 outcome measures: therapeutic inertia, herding, and errors in risk
      stratification knowledge translated into action (ERSKTA) based on commonly used
      stratification tools (Congestive heart failure, Hypertension, Age >=75 years
      (double), Diabetes mellitus, previous Stroke/transient ischemic
      attack/thromboembolism (double), Vascular disease, Age 65-74 years, and female
      gender (score of 0 for males and 1 for female) (CHA2DS2-VASc) and Congestive
      heart failure, Hypertension, Age >=75 years, Diabetes mellitus, and previous
      Stroke/transient ischemic attack (double) (CHADS2)). Logistic regression analysis
      was conducted to determine factors associated with the outcomes. RESULTS:
      Overall, 149 physicians were invited to participate, of which 88 (59.1%)
      completed the online assessment tool. Cardiology was the most frequent specialty
      (69.3%). Therapeutic inertia was present in 53 participants (60.2%), herding in
      66 (75.0%), and ERSKTA in 46 (52.3%). Therapeutic inertia was inversely
      associated with willingness to take financial risks (odds ratio [OR] .72, 95%
      confidence interval [CI] .59-.89 per point in the financial risk propensity
      score), herding was associated with aversion to ambiguity in the medical domain
      (OR 5.35, 95% CI 1.40-20.46), and ERSKTA was associated with the willingness to
      take risks (OR 1.70, 95% CI 1.15-2.50, per point in score). CONCLUSIONS: Among
      physicians involved in stroke prevention in AF, individual risk preferences and
      aversion to ambiguity lead to therapeutic inertia, herding, and errors in risk
      stratification and subsequent use of oral anticoagulants. Educational
      interventions, including formal training in risk management and decision-making
      are needed.

PMID- 29650383
TI  - Probing Ion Channel Structure and Function Using Light-Sensitive Amino Acids.
AB  - Approaches to remotely control and monitor ion channel operation with light are
      expanding rapidly in the biophysics and neuroscience fields. A recent development
      directly introduces light sensitivity into proteins by utilizing photosensitive
      unnatural amino acids (UAAs) incorporated using the genetic code expansion
      technique. The introduction of UAAs results in unique molecular level control
      and, when combined with the maximal spatiotemporal resolution and poor
      invasiveness of light, enables direct manipulation and interrogation of ion
      channel functionality. Here, we review the diverse applications of light
      sensitive UAAs in two superfamilies of ion channels (voltage- and ligand-gated
      ion channels; VGICs and LGICs) and summarize existing UAA tools, their mode of
      action, potential, caveats, and technical considerations to their use in
      illuminating ion channel structure and function.

PMID- 29650384
TI  - The effect of combined drugs therapy on the course of clinical rabies infection
      in a murine model.
AB  - Rabies is a fatal disease of all mammals causing almost 60,000 human deaths every
      year. To date, there is no effective treatment of clinical rabies once the
      symptoms appear. Here, we describe the promising effect of combination therapy
      composed of molecules that target replication of the rabies virus (RV) at
      different stages of life cycle and molecules that inhibit some pathways of the
      innate host immune response accompanied by a blood-brain barrier opener on the
      outcome of RV infection. The study reports statistically significant extension of
      survival of mice treated with the drug cocktail containing T-705, ribavirin,
      interferon alpha/beta, caspase-1 inhibitor, TNF-alpha inhibitor, MAPKs inhibitor
      and HRIG compared to the survival of mice in the virus control group (p =
      0.0312). Furthermore, the study points to the significant impact of interferon
      alpha/beta on the survival of RV-infected mice. We have shown a significant down
      regulation of pro-inflammatory molecules (caspase-1 and TNF-a) in the CNS in RV
      infected mice treated with a combination of drugs including interferon
      alpha/beta.

PMID- 29650385
TI  - Distribution of invasive Streptococcus pneumoniae serotypes before and 5 years
      after the introduction of 10-valent pneumococcal conjugate vaccine in Brazil.
AB  - BACKGROUND: In March 2010, the 10-valent pneumococcal conjugate vaccine (PCV10)
      was introduced into the routine immunization program in Brazil. We describe the
      pneumococcal serotypes that caused invasive pneumococcal diseases (IPD) before
      and after the introduction of PCV10 using data from a national laboratory-based
      surveillance system. METHOD: We compared the prevalence of vaccine types (VT) and
      non-vaccine types (NVT) of Streptococcus pneumoniae in three periods, pre-PCV10
      (January/2005-December/2009), early post-PCV10 (January/2010-December/2013), and
      late post-PCV10 (January/2014-December/2015), by episode in meningitis and non
      meningitis cases and by age group. Changes in serotype prevalence in the early
      and late post-PCV10 periods were determined using pre-PCV10 period as a
      reference. RESULTS: A total of 8971 IPD isolates from patients aged 2 months to
      99 years were analyzed. In the late post-PCV10 period, the VT-IPD reduction in
      the 2-month to 4-year age group was 83.4% for meningitis and 87.4% for non
      meningitis cases; in the age groups 5-17 years, 18-64 years, and >=65 years, VT
      declined by 56.1%, 54.1%, and 47.4%, respectively, in meningitis cases, and by
      60.9%, 47.7%, and 53.4%, respectively, in non-meningitis cases. NVT-IPD increased
      throughout the study period, driven mainly by serotypes 3, 6C, and 19A, which
      remained the predominant types causing IPD in the late post-PCV10 period.
      CONCLUSION: We observed direct and indirect PCV10 protection against IPD caused
      by VT and a shift in the distribution of serotypes 5 years after the introduction
      of PCV10. Continued IPD surveillance is needed to evaluate the sustainability of
      the high prevalence of serotypes 3, 6C, and 19A, which were not included in
      PCV10.

PMID- 29650386
TI  - Human papillomavirus vaccination coverage among females and males, National
      Health and Nutrition Examination Survey, United States, 2007-2016.
AB  - BACKGROUND: Human papillomavirus (HPV) vaccination has been routinely recommended
      at age 11-12 years in the United States for females since 2006 and males since
      2011. Coverage can be estimated using self/parent-reported HPV vaccination
      collected in the National Health and Nutrition Examination Survey (NHANES) for a
      wider age range than other national surveys. We assessed vaccination coverage in
      2015-2016, temporal trends by age, and the validity of self/parent-reported
      vaccination status. METHODS: Participants aged 9-59 years completed an interview
      collecting demographic and vaccination information. Weighted coverage was
      estimated for two-year NHANES cycles by age group for 2007-2008 to 2015-2016 for
      females (N = 14318) and 2011-2012 to 2015-2016 for males (N = 7847). Temporal
      trends in coverage were assessed from 2007-2008 to 2011-2012 for females and from
      2011-2012 to 2015-2016 for both sexes. Sensitivity and specificity of self/parent
      reported vaccination were assessed using provider-verified vaccination records
      from a pilot study in 14-29 year-olds. RESULTS: In 2015-2016, >=1 dose coverage
      among females was highest in 14-19 (54.7%) and 20-24 (56.0%) year-olds and lower
      in successively older age groups. Among males, >=1 dose coverage was highest in
      14-19 year-olds (39.5%) and lower at older ages. Coverage was similar in 9-13
      year-old females and males. Between 2007-2008 and 2011-2012, there were increases
      among females younger than 30 years. Between 2011-2012 and 2015-2016, there were
      increases among female age groups including 20-39 year-olds; male coverage
      increased among ages 9-13, 14-19, and 20-24 years. Self/parent-reported receipt
      of >=1 dose had a sensitivity and specificity of 87.0% and 83.3%. Performance was
      lower for 3 doses. CONCLUSIONS: While overall HPV vaccination coverage remains
      low, it is higher in females than males, except in 9-13 year-olds. There have
      been increases in coverage among many age groups, but coverage has stalled in
      younger females. Adequate validity was demonstrated for self/parent-reported
      vaccination of >=1 dose, but not 3 doses, in a pilot study.

PMID- 29650387
TI  - TPF induction chemotherapy followed by concurrent chemoradiotherapy for locally
      advanced nasopharyngeal carcinoma: Long term results of a Tunisian series.
AB  - PURPOSE: We represent in this study the long term results of docetaxel, cisplatin
      and 5-fluorouracil induction chemotherapy followed by concurrent
      chemoradiotherapy in Tunisian patients with locally advanced nasopharyngeal
      carcinoma. The objective of our study is to analyse the efficacy as well as the
      toxicity of this therapeutic protocol. PATIENTS AND METHODS: Between January 2004
      and December 2008, 32 patients with locoregional advanced non metastatic disease
      (T2b or above and/or N1 or above AJCC 2002) were treated in our institution by
      three cycles of docetaxel, cisplatin and 5-fluorouracil induction chemotherapy
      every 21 days followed by concurrent chemoradiotherapy. Conventional radiotherapy
      was delivered using a cobalt 60 machine during 7 weeks with weekly cisplatin
      (40mg/m2). RESULTS: Twenty-nine patients (90%) had presented an objective
      clinical response in lymph nodes after neoadjuvant chemotherapy, with a complete
      response in 28%. Acute toxicity of docetaxel, cisplatin and 5-fluorouracil
      induction chemotherapy was dominated by vomiting (59%), asthenia (40.6%),
      diarrhea (34.4%) and febrile neutropenia (15.6%). The complete response rate
      after the end of treatment was around 80%. The 5 years overall survival and
      disease-free survival were respectively 68.2% and 67.5%. CONCLUSION: Our results,
      in this field of study, are encouraging with acceptable toxicity despite the lack
      of intensity-modulated radiotherapy technique in our institution during the
      period of study.

PMID- 29650388
TI  - Evaluation at 3 years of concurrent bevacizumab and radiotherapy for breast
      cancer: Results of a prospective study.
AB  - PURPOSE: To determine the 3 years late toxicity among patients with non
      metastatic breast cancer who received concurrent bevacizumab and locoregional
      radiotherapy. MATERIAL AND METHODS: This is a single-arm, multicentre,
      prospective study, of the toxicity of adjuvant concomitant association of
      bevacizumab and radiotherapy in patients with breast cancer. Toxicity was
      assessed by the Common Terminology Criteria for Adverse Events version 3.0 during
      the radiotherapy and follow-up clinics at 12 and 36 months after its completion.
      The study was designed to evaluate the toxicity at one year, 3 years and 5 years.
      RESULTS: Sixty-four patients were included from October 2007 to August 2010. All
      of them received concurrent adjuvant radiotherapy and bevacizumab (in 24 cases
      after primary systemic treatment). All patients received non-fractionated
      radiotherapy to breast or chest wall with or without irradiation of regional
      lymph nodes. Early toxicity has been previously reported. Median follow-up was
      46.4 months (range: 18-77 months). Median age was 53 years old (range: 23-68
      years). The 3-years overall survival was 93% (range: 87-100%). Evaluation of the
      toxicity at 3 years was available for 67% of the patients. There was a low rate
      of toxicity: 14% grade 1 pain, 9% grade 1 fibrosis, 2% grade 1 telangiectasia, 2%
      grade 1 paresis, 7% grade 1 lymphedema and 2% grade 3 lymphedema. No grade 4
      toxicity was observed. No patient had a left ventricular ejection fraction below
      50% at 3 years. CONCLUSIONS: Concurrent bevacizumab with locoregional
      radiotherapy is associated with acceptable 3-years toxicity in patients with
      breast cancer.

PMID- 29650389
TI  - [Inflammatory and immune biomarkers of radiation response].
AB  - In radiotherapy, the treatment is adapted to each individual to protect healthy
      tissues but delivers most of time a standard dose according to the tumor
      histology and site. The only biomarkers studied to individualize the treatment
      are the HPV status with radiation dose de-escalation strategies, and tumor
      hypoxia with dose escalation to hypoxic subvolumes using FMISO- or FAZA-PET
      imaging. In the last decades, evidence has grown about the contribution of the
      immune system to radiation tumor response. Many preclinical studies have
      identified some of the mechanisms involved. In this context, we have realised a
      systematic review to highlight potential inflammatory and immune biomarkers of
      radiotherapy response. Some are inside the tumor microenvironment, as lymphocyte
      infiltration or PD-L1 expression, others are circulating biomarkers, including
      different types of hematological cells, cytokines and chemokines.

PMID- 29650391
TI  - Convergent Evolution in Intracellular Elements: Plasmids as Model Endosymbionts.
AB  - Endosymbionts are organisms that live inside the cells of other species. This
      lifestyle is ubiquitous across the tree of life and is featured by unicellular
      eukaryotes, prokaryotes, and by extrachromosomal genetic elements such as
      plasmids. Given that all of these elements dwell in the cytoplasm of their host
      cell, they should be subject to similar selection pressures. Here we show that
      strikingly similar features have evolved in both bacterial endosymbionts and
      plasmids. Since host and endosymbiont are often metabolically tightly
      intertwined, they are difficult to disentangle experimentally. We propose that
      using plasmids as tractable model systems can help to solve this problem, thus
      allowing fundamental questions to be experimentally addressed about the ecology
      and evolution of endosymbiotic interactions.

PMID- 29650390
TI  - (18F)-FDG PET/CT parameters to predict survival and recurrence in patients with
      locally advanced cervical cancer treated with chemoradiotherapy.
AB  - PURPOSE: To identify predictive (18F)-fluorodeoxyglucose (FDG) positron emission
      tomography (PET)/computed tomography (CT)-based parameters for locoregional
      control, disease-free survival and overall survival, by testing different
      thresholds of metabolic tumor volume and total lesion glycolysis in patients with
      locally-advanced cervical cancer. PATIENTS AND METHODS: Thirty-seven patients
      treated with standard chemoirradiation underwent a pretreatment (18F)-FDG-PET/CT.
      Using different thresholds of maximum standardized uptake value, the following
      PET parameters were computed: maximum standardized uptake value, mean
      standardized uptake value, metabolic tumor volume and total lesion glycolysis for
      primary tumor and lymph nodes and a new parameter combining the metabolic tumor
      volume and the distance between lymph nodes and the primary tumor, namely
      metabolic node distance. Correlation between PET and clinical parameters with
      clinical outcome (overall survival, disease-free survival, and locoregional
      control) was assessed using univariate and multivariate analyses (Cox model).
      RESULTS: In univariate analyses, PET/CT parameters associated with overall
      survival and disease-free survival were: metabolic tumor volume and total lesion
      glycolysis of the primary tumor, total lesion glycolysis of lymph nodes and
      metabolic node distance. The most predictive threshold segmentation for metabolic
      tumor volume and total lesion glycolysis was 48% of maximum standardized uptake
      value for the primary tumor and 30% for the lymph nodes. In multivariate Cox
      analysis, the total lesion glycolysis of primary tumor 48% and metabolic node
      distance were the two independent risk factors for overall survival (P<0.01),
      disease-free survival (P<0.01) and locoregional control (P=0.046). CONCLUSION:
      Total lesion glycolysis of primary tumor and distance between the invaded
      positive lymph node and the primary tumor seem to have the highest predictive
      value when compared to classical clinical prognostic parameters and may be useful
      to identify high risk groups at time of diagnosis and to tailor the therapeutic
      approach in locally-advanced cervical cancer.

PMID- 29650392
TI  - Phage Aggregation-Dispersion by Ions: Striving beyond Antibacterial Therapy.
AB  - Bacteriophages sense alkaline cations in their immediate extracellular
      environment, which regulates virion-virion interactions. An ion-steerable
      aggregation-dispersion (A/D) phenomenon among virions is a recently discovered
      step in group behavior in the phage life cycle. When powered by the octanol-based
      water-immiscible lipopolysaccharide (LPS) trap (oWILT) purification approach, A/D
      promises breakthroughs for a plethora of biotechnological applications beyond
      phage therapy.

PMID- 29650394
TI  - Research Long-term Cognitive Impairment After Off-Pump Versus On-Pump Cardiac
      Surgery: Involved Risk Factors.

PMID- 29650393
TI  - [Neoadjuvant chemotherapy with concurrent chemoradiotherapy in the treatment of
      nasopharyngeal cancer: Southern Tunisian experience].
AB  - PURPOSE: A retrospective study to evaluate the efficacy and safety of the
      addition of neoadjuvant chemotherapy to concurrent chemoradiotherapy in the
      treatment of nasopharyngeal carcinoma. PATIENTS AND METHODS: Data from 62
      patients treated for non-metastatic nasopharyngeal carcinoma were analyzed by
      comparing two groups of patients: a first group of 32 patients treated with 3
      cycles of neoadjuvant chemotherapy based on docetaxel, cisplatin and 5-fluoro
      uracil every 21 days followed by concurrent chemoradiotherapy (weekly cisplatin
      40mg/m2 with radiotherapy 70Gy, 2Gy per session, 5 sessions per week) and a
      second group of 30 patients treated with the same concurrent chemoradiotherapy.
      RESULTS: After a median follow-up of 53.5 months, neoadjuvant chemotherapy showed
      a significant reduction in the rate of a distant metastatic relapses (3.3% vs.
      10%, P=0.03). No significant difference in disease-free survival at 5 years
      (65.6% vs. 68.8%, P=0.46) or overall survival at 5 years (68.8% vs. 73.3%,
      P=0.46) was noted between the two groups. Induction chemotherapy was associated
      with febrile neutropenia of 15.6%. During concurrent chemoradiotherapy,
      hematological complications were greater in the first chemotherapy group (53% vs.
      33%). CONCLUSION: Induction chemotherapy by docetaxel, cisplatin and 5-fluoro
      uracil is a safe and effective option in the treatment of nasopharyngeal
      carcinoma. A better definition of high risk of relapse group would optimize the
      indications of this chemotherapy in the therapeutic arsenal.

PMID- 29650395
TI  - Changing Diet and Physical Activity in Nurses: A Pilot Study and Process
      Evaluation Highlighting Challenges in Workplace Health Promotion.
AB  - OBJECTIVE: To use the Reach, Effectiveness, Adoption, Implementation, and
      Maintenance framework to evaluate and understand key implementation and context
      factors of a diet and physical activity (PA) workplace intervention for nurses.
      METHODS: A 3-month pilot intervention was developed to promote diet and PA
      behavior through self-monitoring, goal setting, and social support using
      pedometers, a smartphone app, and a dedicated Facebook group. Measures included
      diet quality, daily PA, adoption, and implementation (including qualitative
      data). Maintenance was assessed at 6-month follow-up. RESULTS: Forty-seven nurses
      participated in the study. At 3 months, fruit and vegetable intake significantly
      increased (P = .04) whereas PA significantly decreased (P = .01). The
      intervention was partially adopted as planned, with low reach and efficacy.
      Participants reported that changing 2 behaviors at the same time was difficult,
      with the majority feeling it was easier to change diet than to become more
      physically active. CONCLUSIONS AND IMPLICATIONS: The ability to change diet and
      PA behaviors at the same time was challenging in nurses. Future studies examining
      whether similar occupational groups with high stress, fatigue, and lack of time
      face the same challenges would contribute to understanding these results.

PMID- 29650396
TI  - Association between acidosis and outcome in out-of-hospital cardiac arrest
      patients.

PMID- 29650397
TI  - Assessment of five different probes for lung ultrasound in critically ill
      patients: A pilot study.
AB  - INTRODUCTION: The present study was aimed at comparing the diagnosis concordance
      of five echo probes of lung ultrasound (LUS) with CT scans in intensive care and
      emergency patients with acute respiratory failure. MATERIALS: This prospective,
      observational, pilot study involved 10 acute patients in whom a thoracic CT scan
      was performed. An expert performed an LUS reference exam using five different
      probes: three probes with a high-quality conventional echo machine (cardiac
      phased-array probe, abdominal convex probe, linear probe) and two probes (cardiac
      and linear) with a pocket ultrasound device (PUD). Then, a trained physician and
      a resident performed 'blinded' analyses by viewing the video results on a
      computer. The primary objective was to test concordance between the blinded echo
      diagnosis and the CT scan. RESULTS: In the 100 LUS performed, the phased-array
      probe of the conventional machine and linear array probe of the PUD have the best
      concordance with the CT scan (Kappa coefficient=0.75 [CI 95%=0.54-0.96] and 0.62
      [CI 95%=0.37-0.86], respectively) only for experts and trained physicians. The
      agreement was always poor for residents. Convex (abdominal) and linear
      transducers of conventional machines and the phased-array transducers (cardiac)
      of PUD have poor or very poor agreement, regardless of the physician's
      experience. CONCLUSION: Among the probes tested for LUS in acute patients, the
      cardiac probe of conventional machines and the linear probes of PUDs provide good
      diagnosis concordance with CT scans when performed by an expert and trained
      physician, but not by residents.

PMID- 29650398
TI  - The role of optical coherence tomography in the setting of acute myocardial
      infarction.
AB  - In recent years, intravascular imaging-guided percutaneous coronary intervention
      (PCI) has been increasing in patients with acute myocardial infarction (AMI).
      However, the role of optical coherence tomography (OCT) has not been established
      in the setting of AMI despite OCT providing superior resolution (10MUm axial
      resolution) and facilitating assessment of baseline lesion characteristics and
      post-intervention evaluation of the acute result of stent implantation, including
      visualization of procedural dissections, malapposition, tissue prolapse, and
      thrombus. We provide an overview of the potential benefits of OCT-guidance in
      various situations of AMI.

PMID- 29650399
TI  - Superiority of novel automated assessment of aortic annulus by intraoperative
      three-dimensional transesophageal echocardiography in patients with severe aortic
      stenosis: Comparison with conventional cross-sectional assessment.
AB  - BACKGROUND: Previous studies have demonstrated that three-dimensional (3D)
      transesophageal echocardiography (TEE) is an alternative to multi-detector
      computed tomography (MDCT) for aortic valve sizing in transcatheter aortic valve
      replacement (TAVR). However, conventional cross-sectional analysis of aortic
      annulus by 3D TEE has some limitations such as lengthy analytical time. A novel
      software for automated valve measurement has been developed for 3D TEE. We
      evaluated the accuracy and analytical time of aortic annular measurements using
      this novel automated software in the clinical setting. METHODS: We
      retrospectively studied 43 patients with symptomatic severe aortic stenosis (AS)
      who underwent TAVR. All patients underwent intraoperative TEE and MDCT. We
      measured aortic annular area by automated, semi-automated, and cross-sectional
      methods using 3D TEE datasets. These measurements were compared to the
      corresponding MDCT reference values. We also compared the analytical time of the
      three methods. RESULTS: Automated and semi-automated analyses required
      significantly shorter analytical time compared to cross-sectional analysis
      (automated: 30.1+/-5.79s, semi-automated: 74.1+/-15.0s, manual: 81.8+/-18.5s,
      p<0.05). Compared to MDCT measurement (393.7+/-81.0mm2), annular areas measured
      by automated and cross-sectional methods were significantly smaller (automated:
      380.6+/-77.1mm2, cross-sectional: 374.7+/-76.8mm2, p<0.05), while that obtained
      by semi-automated method was not significantly different (387.7+/-75.8mm2).
      Annular areas determined by semi-automated and cross-sectional analyses had
      narrower limits of agreement (LOA) with MDCT measurements, compared to automated
      analysis (automated: -68.6 to 94.7mm2, semi-automated: -48.3 to 60.2mm2, cross
      sectional: -40.0 to 77.9mm2). Measurements by all three methods using 3D TEE
      showed high correlation with MDCT measurement (automated: r=0.86, semi-automated:
      r=0.94, cross-sectional: r=0.93). CONCLUSIONS: For aortic annular measurements
      using 3D TEE in AS patients, semi-automated analysis using the novel automated
      software reduced analytical time while maintaining similar accuracy compared to
      the conventional cross-sectional analysis. This automated software may have
      acceptable feasibility in the clinical setting.

PMID- 29650400
TI  - Corrigendum to "Serum cystatin C levels are associated with coronary artery
      calcification in women without chronic kidney disease" [J. Cardiol. 70 (2017) 559
      564].

PMID- 29650401
TI  - Opthalmological sequelae due to paintball injuries: Case studies.
AB  - OBJECTIVE: Describe the ophthalmological sequelae of patients diagnosed with
      blunt eye injury by paintball. MATERIAL AND METHODS: There were a total 14 cases
      with a diagnosis of blunt trauma by paintball were treated at the ophthalmology
      emergency department of the Barraquer Clinic in Bogota, Colombia. All patients
      underwent a complete ophthalmological examination with their respective controls
      according to their outcome. RESULTS: The frequency of eye trauma by paintball was
      3.01%. Fourteen eyes were evaluated, age range from 9 to 49 years. Cases were
      unilateral, 1 woman and 13 men, initial visual acuity less than 20/30 in 12 eyes.
      Only 5 eyes progressed satisfactorily, and 3 were surgically intervened. The
      cases that did not show any improvement in visual acuity were related to
      posterior pole problems, with the most frequent being macular alterations,
      choroidal rupture, choroidal detachment, retinal tear, and retinal folds. In
      3eyes, clinical improvement of visual acuity was evidenced secondary to
      haemorrhagic processes that resolved with medical treatment. One of them
      underwent surgical treatment of the lens with an intraocular lens implant. In
      2eyes, the visual recovery was very satisfactory and 100% in another. CONCLUSION:
      Paintball has increased as a sport and recreational activity, where paint
      projectiles are fired with compressed air weapons. It carries risks of suffering
      various trauma that can lead to catastrophic episodes, in terms of visual health,
      and repercussions on the quality of life of those affected.

PMID- 29650402
TI  - Proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor use in the
      management of resistant hypercholesterolemia induced by mitotane treatment for
      adrenocortical cancer.
AB  - We report the case of a patient with probable heterozygous familial
      hypercholesterolemia and mitotane-induced resistant hypercholesterolemia, despite
      combination therapy with rosuvastatin and ezetimibe. The patient was managed with
      the addition of evolocumab. Use of a proprotein convertase subtilisin-kexin type
      9 inhibitor, should be considered in patients who develop mitotane-related
      hypercholesterolemia that cannot be managed with conventional lipid-lowering
      treatment.

PMID- 29650403
TI  - Is age a risk factor for depression among the oldest old with cancer?
AB  - INTRODUCTION: Age is negatively related to depression among young and middle age
      patients with cancer. Nevertheless the relationship between age and depression
      among older patients with cancer is unclear. The goal of the current study is to
      assess the association of depression with increasing age among older patients
      with cancer. MATERIALS AND METHODS: Participants were 243 oncology out-patients,
      aged >=65, either receiving treatment for active disease or within 6 months of
      completing treatment for active disease, with a Karnofsky score >=70.
      Participants were grouped by age: "Younger-Old" - age 65-74 (N = 125); "Old" -
      age 75-84 (N = 49); and "Oldest-Old" -age >= 85 years (N = 69). Background data
      included: socio-demography; cancer type/staging/treatment; Charlson comorbidity
      index (CCI); Eastern Cooperative Oncology Group (ECOG) performance. Psychological
      data included: the 5-item Geriatric Depression Scale (GDS); "Distress
      Thermometer" (single item); and Cancer Perceived Agents of Social Support (12
      item). RESULTS: Depression levels were significantly higher among oldest-old
      participants in comparison to the old and younger-old groups: mean GDS scores
      were 0.93 +/- 1.13, 1.27 +/- 1.41 and 3.91 +/- 1.35 respectively. After
      controlling for all potential confounders in a hierarchical logistic regression
      model, age-group significantly predicted both depression and distress. Receiver
      operating characteristic (ROC) analysis determined age 86 as the optimal cutoff
      for both clinical depression and distress. DISCUSSION: Depression among older
      patients with cancer rises with increasing age, being extremely common among the
      oldest old. Age independently predicted depression, irrespective of medical
      variables, social support, or functional status. Findings highlight the
      importance of addressing the potentially unmet psychological needs of this
      rapidly growing patient population.

PMID- 29650405
TI  - The use of laryngeal mask airway for adenoidectomy.

PMID- 29650404
TI  - Stereotactic ablative radiotherapy after concomitant chemoradiotherapy in non
      small cell lung cancer: A TITE-CRM phase 1 trial.
AB  - BACKGROUND AND PURPOSE: Platinum based chemoradiotherapy is the standard of care
      for inoperable non-small cell lung cancer (NSCLC). With evidence that NSCLC can
      have a dose dependent response with stereotactic ablative radiotherapy (SABR), we
      hypothesize that a SABR boost on residual tumor treated with chemoradiotherapy
      could increase treatment efficacy. The purpose of this study was to determine
      feasibility of such an approach. MATERIAL AND METHODS: A prospective phase I
      trial was performed including 26 patients. Time-to-event continual reassessment
      method (TITE-CRM) was used for dose escalation which ranged from 3 * 7 to 3 * 12
      Gy for the stereotactic boost, after 46 Gy (2 Gy per day) of chemoradiotherapy.
      RESULTS: Median follow-up was of 37.1 months (1.7-60.7), and 3, 4, 3, 3, 9 and 4
      patients were included at the dose levels 1, 2, 3, 4, 5 and 6, respectively.
      During chemoradiotherapy, 9 patients experienced grade 3 toxicity. After
      stereotactic radiotherapy, 1 patient experienced an esophageal fistula (with
      local relapse) at the 3 * 11 Gy level, and 1 patient died from hemoptysis at the
      3 * 12 Gy level. The 2-year rate of local control, locoregional free survival,
      metastasis-free survival, and overall survival was 70.3%, 55.5%, 44.5% and 50.8%,
      respectively. CONCLUSION: In the treatment of NSCLC with chemoradiotherapy
      followed by a stereotactic boost, the safe recommended dose in our protocol was a
      boost dose of 3 * 11 Gy.

PMID- 29650406
TI  - Crisis of COPD in China: the future is now.

PMID- 29650407
TI  - Chronic obstructive pulmonary disease in China: a nationwide prevalence study.
AB  - BACKGROUND: Because of the rapid change in economic development and lifestyle in
      China, and the ageing population, concerns have grown that chronic obstructive
      pulmonary disease (COPD) could become epidemic. An up-to-date nationwide
      estimation of COPD prevalence in China is needed. METHODS: We did a cross
      sectional survey of a nationally representative sample of individuals from
      mainland China aged 40 years or older. The primary outcome was COPD, defined
      according to the 2017 Global Initiative for Chronic Obstructive Lung Disease
      (GOLD) lung function criteria. FINDINGS: Between Dec 29, 2014, and Dec 31, 2015,
      66 752 adults were recruited to the study population. The estimated standardised
      prevalence of COPD was 13.6% (95% CI 12.0-15.2). The prevalence of COPD differed
      significantly between men and women (19.0%, 95% CI 16.9-21.2 vs 8.1%, 6.8-9.3;
      p<0.0001), mainly because of a significant difference in smoking status between
      men and women (current smokers 58.2% vs 4.0%). The prevalence of COPD differed by
      geographic region, with the highest prevalence in southwest China (20.2%, 95% CI
      14.7-25.8) and the lowest in central China (10.2%, 8.2-12.2). Among adults with
      COPD, 56.4% (95% CI 53.7-59.2) had mild disease (GOLD stage I), 36.3% (34.3-38.3)
      had moderate disease (GOLD stage II), 6.5% (5.5-7.4) had severe disease (GOLD
      stage III), and 0.9% (0.6-1.1) had very severe disease (GOLD stage IV).
      INTERPRETATION: In a large, nationally representative sample of adults aged 40
      years or older, the estimated overall prevalence of COPD in China in 2014-15 was
      13.6%, indicating that this disease has become a major public-health problem.
      Strategies aimed at prevention and treatment of COPD are needed urgently.
      FUNDING: Chinese Central Government, the Ministry of Science and Technology of
      The People's Republic of China, and the National Natural Science Foundation of
      China.

PMID- 29650409
TI  - Advances in ex-vivo donor lung organ care.

PMID- 29650410
TI  - Assessment of intersegmental coordination of rats during walking at different
      speeds - Application of continuous relative phase.
AB  - The present study investigated the feasibility and reliability of continuous
      relative phase (CRP) and deviation phase (DP) to assess intersegmental hind limb
      coordination pattern and coordination variability in rats during walking. Twenty
      six adult rats walked at 8 m/min, 12 m/min and 16 m/min while two-dimensional
      kinematics were recorded. Segment angles and segment angular velocities of the
      paw, shank and thigh on the left hind-limb were extracted from 15 strides and CRP
      was calculated for the paw-shank and shank-thigh coupling. The effect of walking
      speed on the time point average curve of the CRP (ACRP) and DP and on the mean
      ACRP and mean DP was established by statistical parametric mapping (SPM) and a
      one-way ANOVA for repeated measures. Absolute and relative reliability were
      assessed by measurement error and intra-class correlation coefficient. The SPM
      analysis revealed time dependent differences in the effect of speed. Thus, the
      CRP of the paw-shank coupling decreased with increasing speed during most of the
      gait cycle while the CRP of the shank-thigh coupling was decreased during the
      swing phase. The session-to-session reliability was fair to good for the
      coordination measure and poor for the variability measure.

PMID- 29650408
TI  - Normothermic ex-vivo preservation with the portable Organ Care System Lung device
      for bilateral lung transplantation (INSPIRE): a randomised, open-label, non
      inferiority, phase 3 study.
AB  - BACKGROUND: Severe primary graft dysfunction (PGD) of grade 3 (PGD3) is a common
      serious complication following lung transplantation. We aimed to assess
      physiological donor lung preservation using the Organ Care System (OCS) Lung
      device compared with cold static storage. METHODS: In this non-inferiority,
      randomised, controlled, open-label, phase 3 trial (INSPIRE) recipients were aged
      18 years or older and were registered as standard criteria primary double lung
      transplant candidates. Eligible donors were younger than 65 years old with a
      ratio of partial pressure of oxygen in arterial blood to the fraction of inspired
      oxygen of more than 300 mm Hg. Transplant recipients were randomly assigned (1:1)
      with permuted blocks, stratified by centre, to receive standard criteria donor
      lungs preserved in the OCS Lung device (OCS arm) or cold storage at 4 degrees C
      (control arm). The composite primary effectiveness endpoint was absence of PGD3
      within the first 72 h after transplant and 30-day survival in the per-protocol
      population, with a stringent 4% non-inferiority margin. Superiority was tested
      upon meeting non-inferiority. The primary safety endpoint was the mean number of
      lung graft-related serious adverse events within 30 days of transplant. We did
      analyses in the per-protocol and intention-to-treat populations. This trial is
      registered with ClinicalTrials.gov, number NCT01630434. FINDINGS: Between Nov 17,
      2011, and Nov 24, 2014, we randomly assigned 370 patients, and 320 (86%)
      underwent transplantation (n=151 OCS and n=169 control); follow-up was completed
      in Nov 24, 2016. The primary endpoint was met in 112 (79.4%) of 141 patients (95%
      CI 71.8 to 85.8) in the OCS group compared with 116 (70.3%) of 165 patients (62.7
      to 77.2) in the control group (non-inferiority point estimate -9.1%; 95% CI 
      infinity to -1.0; p=0.0038; and superiority test p=0.068). Patient survival at
      day 30 post-transplant was 135 (95.7%) of 141 patients (95% CI 91.0-98.4) in the
      OCS group and 165 patients (100%; 97.8-100.0) in the control group (p=0.0090) and
      at 12 months was 126 (89.4%) of 141 patients (83.1-93.9) for the OCS group
      compared with 146 (88.1%) of 165 patients (81.8-92.8) for the control group.
      Incidence of PGD3 within 72 h was reported in 25 (17.7%) of 141 patients in the
      OCS group (95% CI 11.8 to 25.1) and 49 (29.7%) of 165 patients in the control
      group (22.8 to 37.3; superiority test p=0.015). The primary safety endpoint was
      met (0.23 lung graft-related serious adverse events in the OCS group compared
      with 0.28 events in the control group [point estimate -0.045%; 95% CI -infinity
      to 0.047; non-inferiority test p=0.020]). In the intention-to-treat population,
      causes of death at 30 days and in hospital were lung graft failure or lung
      infection (n=2 for OCS vs n=7 for control), cardiac causes (n=4 vs n=1), vascular
      or stroke (n=3 vs n=0), metabolic coma (n=0 vs n=2), and generalised sepsis (n=0
      vs n=1). INTERPRETATION: The INSPIRE trial met its primary effectiveness and
      safety endpoints. Although no short-term survival benefit was reported, further
      research is needed to see whether the reduced incidence of PGD3 within 72 h of a
      transplant might translate into earlier recovery and improved long-term outcomes
      after lung transplantation. FUNDING: TransMedics Inc.

PMID- 29650411
TI  - Interfacial mechanical behaviour of protein-mineral nanocomposites: A molecular
      dynamics investigation.
AB  - Biological composite materials, such as bone, tooth and nacre, are comprised of a
      mixture of nano-sized hard components (e.g. mineral platelets) and soft
      components (e.g. protein molecules). Their mechanical behaviour greatly depends
      on the protein-mineral interfaces. This paper investigates the effects of mineral
      surface nanostructures on the interfacial interaction and mechanical behaviour of
      protein-mineral nanocomposites. Interfacial shear between osteopontin (OPN) and
      hydroxyapatite (HA) mineral layers with surface nanostructures is investigated
      using the atomistic molecular dynamics (MD) simulations. The results indicate
      that the OPN residues can be attached to HA surfaces but the surface
      nanostructures greatly affect the interfacial interaction and mechanical
      behaviour. The HA layers with a higher number of nano-sized grooves (defects)
      increase the surface roughness but reduce the pulling force and energy
      dissipation.

PMID- 29650412
TI  - Theoretical considerations for muscle-energy savings during distance running.
AB  - We have recently demonstrated that the triceps surae muscles energy cost (ECTS)
      represents a substantial portion of the total metabolic cost of running (Erun).
      Therefore, it seems relevant to evaluate the factors which dictate ECTS, namely
      the amount and velocity of shortening, since it is likely these factors will
      dictate Erun. Erun and triceps surae morphological and AT mechanical properties
      were obtained in 46 trained and elite male and female distance runners using
      ultrasonography and dynamometry. ECTS (J.stride-1) at the speed of lactate
      threshold (sLT) was estimated from AT force and crossbridge mechanics and
      energetics. To estimate the relative impact of these factors on ECTS, mean values
      for running speed, body mass, resting fascicle length (Lf), Achilles tendon
      stiffness and moment arm and maximum isometric plantarflexion torque were
      obtained. ECTS was calculated across a range (mean +/- 1 sd) of values for each
      independent factor. Average sLT was 233 m.min-1. At this speed, ECTS was 255
      J.stride-1. Estimated fascicle shortening velocity was 0.08 Vmax and the level of
      muscle activation was 84.7% of maximum isometric torque. Compared to the ECTS
      calculated from the lowest range of values obtained for each independent factor,
      higher AT stiffness was associated with a 39% reduction in ECTS, 81% reduction in
      fascicle shortening velocity and a 31% reduction in muscle activation. Longer AT
      moment arms and elevated body masses were associated with an increase in ECTS of
      18% and 23%, respectively. These results demonstrate that a low ECTS is achieved
      primarily from a high AT stiffness and low body mass, which is exemplified in
      elite distance runners.

PMID- 29650413
TI  - Taurine protects against knee osteoarthritis development in experimental rat
      models.
AB  - BACKGROUND: Osteoarthritis (OA) is one of the complex diseases that affect a
      large population of the world. The aim of the current study was to explore the
      roles of taurine in OA rat models, and discover the related mechanisms. METHODS:
      OA rat models were established by anterior cruciate ligament transection (ACLT)
      plus medial meniscus resection (MMx) surgery on the right knees. Secondary
      mechanical allodynia, weight-bearing alterations and knee joint width were
      evaluated before surgery and every two weeks after surgery. At 14weeks,
      histopathological analysis was conducted on the knee joint cartilage. Protein
      amount of MMP-3 and CHOP was evaluated by western blot. RESULTS: Taurine
      injection after surgery significantly relieved the symptoms of OA in rat models
      in a dose-dependent and time-dependent manner, as shown by alleviation of
      secondary mechanical allodynia, decrease in hind limb weight-bearing alterations,
      and inhibited knee swelling. Moreover, histopathological analysis showed that
      taurine inhibited matrix loss and cartilage degeneration in a dose-dependent
      manner. Taurine administration strikingly suppressed the expression of matrix
      metalloproteinase-3 (MMP-3) and CHOP. CONCLUSION: These results indicated that
      taurine administration exhibited protective effects by inhibiting MMP-3 and CHOP
      expression, and subsequently alleviated the OA symptoms in experimental rat
      models.

PMID- 29650414
TI  - Joint Laxity in Preschool Children Born Preterm.
AB  - OBJECTIVE: To evaluate the prevalence of joint laxity in children born preterm
      assessed in the first 2 years, the relationship between joint laxity and motor
      performance at preschool age, and possible changes over time in a subgroup of
      children followed longitudinally. STUDY DESIGN: The revised scale of Beighton
      Score was used to evaluate joint laxity in a population of 132 preschool children
      born preterm between 24 and 32 weeks of gestational age. All were assessed for
      joint laxity between 12 and 24 months of age. Children also performed the
      Movement Assessment Battery for Children-Second Edition between the age of 3
      years and 6 months and 4 years; the age at onset of independent walking also was
      recorded. RESULTS: The total Beighton Score ranged between 0 and 8. Twenty
      percent of the cohort showed joint laxity. No differences related to sex or
      gestational age were observed. Children born preterm with joint laxity achieved
      later independent walking and achieved lower scores on Movement Assessment
      Battery for Children-Second Edition than those without joint laxity. In 76
      children born preterm, an assessment for joint laxity was repeated once between
      25 and 36 months and again after >36 months. No statistically significant
      difference was observed between the 3 assessments. CONCLUSIONS: The Beighton
      Score can be used to assess generalized joint laxity in children born preterm. As
      the presence of joint laxity influenced motor competences, the possibility to
      early identify these infants in the first 2 years is of interest to benefit from
      early intervention and potentially improve gross motor skills and coordination.

PMID- 29650415
TI  - Pulmonary Vein Stenosis in Infants: A Systematic Review, Meta-Analysis, and Meta
      Regression.
AB  - OBJECTIVE: To quantify outcomes of infants (<1 year of age) diagnosed with
      pulmonary vein stenosis (PVS). STUDY DESIGN: MEDLINE (PubMed), Scopus, and Web of
      Science were searched through February 1, 2017, with no language restrictions.
      Publications including infants diagnosed with primary PVS, defined as the absence
      of preceding intervention(s), were considered. The study was performed according
      to Meta-analysis of Observational Studies in Epidemiology guidelines, the
      Systematic Reviews, and Meta-Analysis checklist, and registered prospectively.
      The quality of selected reports was critically examined. Data extraction was
      independently performed by multiple observers with outcomes agreed upon a priori.
      Data were pooled using an inverse variance heterogeneity model with incidence of
      mortality the primary outcome of interest. RESULTS: Forty-eight studies of 185
      infants were included. Studies were highly diverse with regards to the
      participants, interventions, and outcomes reported. The median (range) age at
      diagnosis was 5.0 (0.1-11.6) months. Pooled mortality was 58.5% (95% CI 49.8%
      67.0%, I2 = 21.4%). We observed greater mortality incidence among infants with 3
      or 4 vein stenoses than in those with 1 or 2 vein stenoses (83.3% vs 36.1%; P <
      .01). We observed greater mortality among infants with bilateral than unilateral
      disease (78.7% vs 26.0%; P < .01). CONCLUSIONS: Studies of primary PVS during
      infancy are highly variable in their methodological quality and estimates of
      clinical outcomes; therefore, estimates of prognosis remain uncertain.
      Multicenter, interdisciplinary collaborations, including alignment of key outcome
      measurements, are needed to answer questions beyond the scope of available data.

PMID- 29650416
TI  - Effect of Comorbidities in Stage II/III Colorectal Cancer Patients Treated With
      Surgery and Neoadjuvant/Adjuvant Chemotherapy: A Single-Center, Observational
      Study.
AB  - BACKGROUND: Comorbidity has a detrimental effect on cancer survival, however, it
      is difficult to disentangle its direct effect from its influence on treatment
      choice. In this study we assessed the effect of comorbidity on survival in
      patients who received standard treatment for resected stage II and III colorectal
      cancer (CRC). PATIENTS AND METHODS: In total, 230 CRC patients, 68 rectal (29.6%)
      and 162 colon cancer (70.4%) treated with surgical resection and
      neoadjuvant/adjuvant chemotherapy from December 2002 to December 2009 at
      Humanitas Cancer Center were retrospectively reviewed. The key independent
      variable was the Charlson Comorbidity Index (CCI) score, measured as a continuous
      variable. The differences between groups for categorical data were tested using
      the chi2 test. Actuarial survival curves were generated using the Kaplan-Meier
      method. RESULTS: Median follow-up was 113 (range, 8.2-145.0) months. Median age
      was 63 (range, 37-78) years. In univariate analysis CCI score was significantly
      associated with poorer disease-free survival (hazard ratio [HR], 1.65; 95%
      confidence interval [CI], 1.52-1.80; P < .001), and overall survival (OS; HR,
      1.55; 95% CI, 1.41-1.71; P < .001). Factors associated with poorer outcome also
      included (stage III vs. stage II, P < .029) and age (age >70 vs. <=70 years, P <
      .001). After adjusting for these factors, a significant negative prognostic role
      of CCI score was still observed (adjusted HR for OS, 1.59; 95% CI, 1.43-1.76; P <
      .001). CONCLUSION: Among CRC patients who underwent surgical resection and
      chemotherapy, a higher CCI score was associated with poorer outcome and might
      predict long-term survival.

PMID- 29650417
TI  - beta-aminoisobutyric acid accelerates the proliferation and differentiation of
      MC3T3-E1 cells via moderate activation of ROS signaling.
AB  - BACKGROUD: Osteoporosis is one of the bone-metabolic diseases associated with
      decreased bone renewal and bone mineral density. beta-aminoisobutyric acid
      (BAIBA), a natural thymine catabolite, can reduce inflammation in skeletal muscle
      and alleviate hepatic endoplasmic reticulum stress. However, the roles of BAIBA
      in osteoblast proliferation and differentiation remain largely unknown. METHODS:
      The cultured MC3T3-E1 cells received various treatments in this study, including
      BAIBA alone, H2O2 alone, BAIBA plus N-acetyl-l-cysteine and BAIBA plus apocynin.
      Cell proliferation was determined by CCK-8 assay and 3H-Thymidine incorporation.
      Cell differentiation was evaluated by determining mRNA level of differentiation
      makers and ALP, and ALP activity. Reactive oxygen species (ROS) were determined
      by DHE staining while superoxide anion level and NAD(P)H oxidase activity were
      determined by the lucigenin-derived chemiluminescence method. The content of
      hydrogen peroxide (H2O2) was detected using a commercial kit. The level of NOX1,
      NOX2 and NOX4 was determined by Western-blot or qRT-PCR. RESULTS: We show that
      treatment of BAIBA stimulated the proliferation of MC3T3-E1 osteoprogenitor cells
      and enhanced the gene expression of osteoblast differentiation markers.
      Incubation of MC3T3-E1 cells with BAIBA evoked increases in NAD(P)H oxidase
      derived reactive oxygen species (ROS). Scavenging of reactive oxygen species (N
      acetyl-l-cysteine) or inhibition of NAD(P)H oxidase (apocynin) abolished the
      BAIBA-elicited proliferation and differentiation of MC3T3-E1 cells. CONCLUSION:
      Our results provide the first evidence that BAIBA stimulates proliferation and
      differentiation of osteoprogenitor cells via activation of NAD(P)H oxidase/ROS
      signaling.

PMID- 29650418
TI  - Inflammatory bowel disease drastically affects the prognosis of patients treated
      for peritoneal metastases with combined cytoreductive surgery and hyperthermic
      intraperitoneal chemotherapy: A multicenter study.
AB  - BACKGROUND: Complete cytoreductive surgery (CCRS) followed by hyperthermic
      intraperitoneal chemotherapy (HIPEC) is a validated treatment in selected
      patients with peritoneal metastases (PM) of intestinal origin. There is an
      increased risk of Colorectal Cancer (CRC) and Small Bowel Adenocarcinoma (SBA) in
      Inflammatory Bowel Disease (IBD). The feasibility and benefit of that surgical
      approach in IBD patients is unknown. METHODS: IBD patients with operated PM
      complicating CRC or SBA were extracted from a French national multicenter
      prospective database of patients who underwent surgery for PM in HIPEC expert
      centers from 1995 to 2016. IBD patients who underwent CCRS plus HIPEC were
      compared with a cohort of 234 patients who had the same surgery for sporadic
      colon cancer. RESULTS: 14 patients (male 57%, median age 40 years, 12 Crohn's
      disease) with CRC (n = 7) and SBA (n = 7) were included. CCRS followed by HIPEC
      (oxaliplatin 72.7%) was performed in 11 cases (median peritoneal cancer index 7;
      range 1-30). The control group had the same characteristics except an older age
      at HIPEC (56.52 vs 45.74; p = 0.003). Overall survival (HR = 4.47; 90% CI, 1.91
      to 10.49), Relapse Free Survival (HR = 2.31; 90% CI, 1.17 to 4.56) and Peritoneal
      Recurrence Free Survival (HR = 3.30; 90% CI, 1.59 to 6.85) were significantly
      lower in IBD patients. Six of the 11 patients presented major surgical morbidity
      with no impact on post-operative treatment. CONCLUSION: CCRS followed by HIPEC is
      less effective in IBD patients with resectable PM complicating CRC or SBA. More
      careful selection of those patients is needed.

PMID- 29650419
TI  - Comparison of pathological complete response rates after neoadjuvant short-course
      radiotherapy or chemoradiation followed by delayed surgery in locally advanced
      rectal cancer.
AB  - INTRODUCTION: Patients with locally advanced rectal cancer (LARC) who are unfit
      for chemoradiation (CRT), are often offered short-course radiotherapy followed by
      delayed surgery (SCRT-delay). This entails a lower radiation dose, no
      chemotherapy and a shorter treatment period. This may lower their chances for
      complete tumor response and, as such, organ-sparing approaches. The purpose of
      this study was to compare the pathological complete response (pCR) rates between
      neoadjuvant CRT and SCRT-delay in patients with LARC in a nationwide database
      from the Netherlands. METHODS: In the population based Netherlands Cancer
      Registry, clinical stage III rectal cancer patients, diagnosed between 2008 and
      2014, who underwent CRT or SCTR-delay were selected. pCR (ypT0N0), near pCR (ypT0
      1N0), and tumor and nodal downstaging were compared between the treatment groups
      using multivariable logistic regression analysis. RESULTS: 386 patients underwent
      SCRT-delay and 3659 patients underwent CRT. The pCR-rate in the SCRT-delay group
      was significantly lower compared to the CRT-group (6.4% vs. 16.2%, p < 0.001).
      After adjustment for clinical tumor stage, clinical nodal stage and time interval
      to surgery, SCRT-delay patients were significantly less likely to reach pCR
      (adjusted odds ratio 0.3, 95%CI 0.2-0.5). Also, near-pCR (ypT0-1N0) as well as
      tumor and nodal downstaging was observed less often in the SCRT-delay group.
      CONCLUSION: Compared to patients treated with neoadjuvant CRT, those receiving
      SCRT and delayed surgery are less likely to develop pCR. Novel neoadjuvant
      treatment strategies for patients not fit enough for CRT are needed to increase
      their eligibility for organ-sparing treatments.

PMID- 29650421
TI  - Financial outcomes of transoral robotic surgery: A narrative review.
AB  - OBJECTIVE: To determine the current cost impact and financial outcomes of
      transoral robotic surgery in Otolaryngology. DATA SOURCES: A narrative review of
      the literature with a defined search strategy using Pubmed, MEDLINE, CINAHL, and
      Web of Science. REVIEW METHODS: Using keywords ENT or otolaryngology, cost or
      economic, transoral robotic surgery or TORs, searches were performed in Pubmed,
      MEDLINE, CINAHL, and Web of Science and reviewed by the authors for inclusion and
      analysis. RESULTS: Six total papers were deemed appropriate for analysis. All
      addressed cost impact of transoral robotic surgery (TORs) as compared to open
      surgical methods in treating oropharyngeal cancer and/or the identification of
      the primary tumor within unknown primary squamous cell carcinoma. Results showed
      TORs to be cost-effective. CONCLUSION: Transoral robotic surgery is currently
      largely cost effective for both treatment and diagnostic procedures. However,
      further studies are needed to qualify long-term data.

PMID- 29650420
TI  - Denosumab treatment of inoperable or locally advanced giant cell tumor of bone -
      Multicenter analysis outside clinical trial.
AB  - BACKGROUND: Giant cell tumor of bone (GCTB) is an osteolytic, locally aggressive,
      rarely metastazing bone tumor. This is a retrospective study evaluating a large
      series of GCTB patients treated with denosumab in routine practice in 6 European
      reference centers. METHODS: Patients with locally advanced, unresectable or
      metastatic GCTB, treated with denosumab outside clinical trials were eligible.
      Primary end-point was progression-free survival (PFS) for all patients; secondary
      end-points were: type of surgery, relapse rate and event-free survival for
      patients after preoperative denosumab + surgery. RESULTS: We identified 138
      patients treated in the period 2011-2016. In 40/43 cases the diagnosis was
      confirmed by H3F3A gene mutation. Median follow-up time was 23 months (range 6
      48). Primary tumor was located in lower limb (38%) - mostly in femur and tibia,
      in upper limb (34%), and in pelvis/axial skeleton/ribs (28%). 110 (80%) patients
      had primary tumors, 28 (22%) recurrent tumors after previous surgical procedures
      (+/- radiotherapy). 89/138 patients had locally advanced GCTB and underwent
      neoadjuvant denosumab. The median denosumab treatment duration was 8 months
      (median number of cycles 11), 98% had clinical benefit from therapy. 39 (44%) had
      wide en-bloc resection - WE (+implantation of the prosthesis in 17 cases), the
      other 50 (56%) cases had intralesional curettage - C. Progression after surgical
      treatment was observed in 19 patients, 16 of them after C (32%); 13 patients
      underwent denosumab re-challenge, and all responded. Two-year progression-free
      survival (PFS; from denosumab start) rate was 81%; 2-year EventFS (from surgery)
      was significantly better in WE group (93%) vs 55% in C group (p = 0.006).
      Treatment was well tolerated with only 2 cases of grade 3 toxicity and one
      osteonecrosis of the jaw. CONCLUSION: Our retrospective study confirms that
      denosumab is extremely efficient in unresectable/metastatic disease as well as in
      a neoadjuvant setting. Our data confirm excellent efficacy and short-term
      tolerability of this drug. Our data suggest that neoadjuvant therapy with
      denosumab is the option for treatment of initially locally advanced tumors to
      facilitate complete surgical resection or avoid mutilating surgery. The risk of
      recurrences after curettage of GCTB following denosumab raises questions about
      the optimal management of such cases.

PMID- 29650422
TI  - In whom does horizontal canal BPPV recur?
AB  - PURPOSE: The objective of this study is to examine the rate of horizontal canal
      BPPV recurrence of the same type and search for predisposing factors.

PMID- 29650423
TI  - A boy presenting with chronic ear drainage and associated middle ear mass.

PMID- 29650425
TI  - Measuring the effect of insecticide resistance: are we making progress?

PMID- 29650424
TI  - Implications of insecticide resistance for malaria vector control with long
      lasting insecticidal nets: a WHO-coordinated, prospective, international,
      observational cohort study.
AB  - BACKGROUND: Scale-up of insecticide-based interventions has averted more than 500
      million malaria cases since 2000. Increasing insecticide resistance could herald
      a rebound in disease and mortality. We aimed to investigate whether insecticide
      resistance was associated with loss of effectiveness of long-lasting insecticidal
      nets and increased malaria disease burden. METHODS: This WHO-coordinated,
      prospective, observational cohort study was done at 279 clusters (villages or
      groups of villages in which phenotypic resistance was measurable) in Benin,
      Cameroon, India, Kenya, and Sudan. Pyrethroid long-lasting insecticidal nets were
      the principal form of malaria vector control in all study areas; in Sudan this
      approach was supplemented by indoor residual spraying. Cohorts of children from
      randomly selected households in each cluster were recruited and followed up by
      community health workers to measure incidence of clinical malaria and prevalence
      of infection. Mosquitoes were assessed for susceptibility to pyrethroids using
      the standard WHO bioassay test. Country-specific results were combined using meta
      analysis. FINDINGS: Between June 2, 2012, and Nov 4, 2016, 40 000 children were
      enrolled and assessed for clinical incidence during 1.4 million follow-up visits.
      80 000 mosquitoes were assessed for insecticide resistance. Long-lasting
      insecticidal net users had lower infection prevalence (adjusted odds ratio [OR]
      0.63, 95% CI 0.51-0.78) and disease incidence (adjusted rate ratio [RR] 0.62,
      0.41-0.94) than did non-users across a range of resistance levels. We found no
      evidence of an association between insecticide resistance and infection
      prevalence (adjusted OR 0.86, 0.70-1.06) or incidence (adjusted RR 0.89, 0.72
      1.10). Users of nets, although significantly better protected than non-users,
      were nevertheless subject to high malaria infection risk (ranging from an average
      incidence in net users of 0.023, [95% CI 0.016-0.033] per person-year in India,
      to 0.80 [0.65-0.97] per person year in Kenya; and an average infection prevalence
      in net users of 0.8% [0.5-1.3] in India to an average infection prevalence of
      50.8% [43.4-58.2] in Benin). INTERPRETATION: Irrespective of resistance,
      populations in malaria endemic areas should continue to use long-lasting
      insecticidal nets to reduce their risk of infection. As nets provide only partial
      protection, the development of additional vector control tools should be
      prioritised to reduce the unacceptably high malaria burden. FUNDING: Bill &
      Melinda Gates Foundation, UK Medical Research Council, and UK Department for
      International Development.

PMID- 29650426
TI  - [Optimisation of measures to protect premature neonates of less than 35 weeks
      from the cold in the first hour of life].

PMID- 29650427
TI  - [Triorchidism in the differential diagnosis of scrotal masses].

PMID- 29650428
TI  - [Extrauterine growth restriction among neonates with a birthweight less than
      1,500grams].
AB  - INTRODUCTION: Growth restriction in preterm infants has been related to a poor
      neurodevelopment outcome. OBJECTIVES: To define the incidence of postnatal growth
      restriction in premature babies <=1,500 grams and to detect related clinical or
      biochemical markers. METHODS: Retrospective longitudinal observational study.
      Multivariate linear regression models were used to determine variables that can
      predict the change in weight z-score during admission. RESULTS: The study
      included 130 patients with a mean birthweight of 1,161+/-251grams and a
      gestational age of 29.9+/-2.5 weeks. At hospital discharge, 59.2% had a weight
      below P10.During admission, the z-scores of weight and length decreased by 
      0.85+/-0.79 and -1.09+/-0.65, respectively.The largest decrease in z-score
      occurred during NICU admission, with a weight gain rate of 6.6+/-8.8g/Kg/day,
      after which growth acceleration took place (16.7+/-3.8g/Kg/day), but was
      insufficient to catch-up.Higher levels of urea were negatively correlated with
      the change in the z-score of weight (P<.001), and a weight <P10 at birth
      positively correlated (P=.013). CONCLUSIONS: More than half of newborns <=1,500
      grams have a weight at discharge of <P10. This growth restriction occurs during
      NICU admission, and affects low birth weight infants less frequently.Urea levels
      correlate negatively with weight gain, which requires further study of the
      relationship between growth and the protein compartment.

PMID- 29650429
TI  - [Emergency department consultations associated with unintentional injuries: A
      cases series].
AB  - OBJECTIVE: To analyse the clinical and epidemiological characteristics of
      children who are attended in Emergency Departments (EDs) for an unintentional
      injury in Spain. METHODS: Multicentre case series with prospective data
      collection conducted during 12 months in the ED of 11 hospitals belonging to the
      Spanish Paediatric Emergency Research Group. Data were collected between
      September 2014 and January 2015, continuing for one year in all paediatric EDs,
      and included children between 0 and 16 years old seen for an unintentional
      injury. RESULTS: A total of 10,175 episodes were recorded during the study, of
      which 1,941 were due to unintentional injuries (19.1%, 95% CI: 18.3%-19.8%), and
      1,673 of these were included in the study. Falling, direct injuries, and injuries
      due to sports activities represented more than 80%, with significant variations
      in the injuries mechanism observed in different age groups. More than occurred at
      home or school. About 40% of the unintentional injuries were not witnessed by an
      adult. The most frequent diagnosis was limb trauma (63.0%), with a fracture being
      observed in 242 (14.4% of unintentional injuries). As regards fractures, 34
      (2.0%) were admitted to hospital, with 21 (61.8%) for surgical reduction of the
      fracture. No deaths were recorded in the first 24h. CONCLUSIONS: Unintentional
      injuries constitute a very common reason for consultation in EDs in Spain. The
      circumstances surrounding the unintentional injuries should be considered, in
      order to develop preventive measures and to improve the training of people
      involved in the care of these children.

PMID- 29650430
TI  - [Cow's milk protein intolerance imitating septic shock in a young infant].

PMID- 29650431
TI  - [Efficacy, safety and satisfaction of sedation-analgesia in Spanish emergency
      departments].
AB  - OBJECTIVES: To offer analgesia and sedation should be a priority in paediatric
      emergency departments. The aim of this study was to determine the effectiveness
      and safety of the sedation-analgesia procedure, as well as the satisfaction of
      the doctors, patients and parents. METHODS: A multicentre, observational, and
      prospective analytical study was conducted on the sedation-analgesia procedure
      performed on children younger than 18 years old in 18 paediatric emergency
      departments in Spain from February 2015 until January 2016. RESULTS: A total of
      658 procedures were recorded. The effectiveness was good in 483 cases (76.1%;
      95%CI: 72.7-79.4%), partial in 138 (21.7%; 95%CI: 18.5-24.9%), and poor in 14
      (2.2%; 95%CI: 1.1-3.4). The effectiveness was better when the doctor in charge
      was an emergency paediatrician (OR: 3.14; 95%CI: 1.10-8.95), and when a deeper
      level of sedation was achieved (OR: 2.37; 95%CI: 1.68-3.35). Fifty two children
      (8.4%) developed adverse drug reactions, more usually gastrointestinal,
      neurological or respiratory ones (89.9% were resolved in <2h). One patient was
      intubated. The older child and a deeper level of sedation were found to be
      independent risk factors for adverse reactions (OR: 1.18; 95%CI: 1.09-1.28 and
      OR: 1.86; 95%CI: 1.22-2.83, respectively). Thirteen children (5%) developed late
      adverse drug reactions, more commonly, dizziness and nauseas. A combination of
      midazolam/ketamine had been used in all the cases (RR: 24.46; 95%CI: 11.78
      50.76). The perceived satisfaction level (0-10) was obtained from 604 doctors
      (mean: 8.54; SD: 1.95), 526 parents (mean: 8.86; SD: 1.49), and 402 children
      (mean: 8.78; SD: 1.70). CONCLUSIONS: The sedation-analgesia procedure performed
      in paediatric emergency departments by trained paediatricians seems to be useful,
      effective and safe, as well as satisfactory for all participants.

PMID- 29650432
TI  - Intestinal obstruction - Not everything is as it seems.

PMID- 29650433
TI  - How heavy is the impact of childhood obesity on cardiovascular risk?

PMID- 29650434
TI  - Importance of three-dimensional speckle tracking in the assessment of left atrial
      and ventricular dysfunction in patients with myotonic dystrophy type 1.
AB  - INTRODUCTION AND AIM: Myotonic dystrophy type 1 (DM1) is a multisystem disease in
      which cardiac involvement is common. The aim of this study was to identify early
      changes in left atrial (LA) mechanics and left ventricular (LV) systolic function
      in patients with myotonic dystrophy type 1 using three-dimensional (3D) speckle
      tracking echocardiography (3D-STE). METHODS: This observational study included 25
      patients with DM1 and 25 healthy volunteers. We assessed LA and LV global strain
      parameters using 3D-STE. RESULTS: Patients with DM1 showed significantly lower
      longitudinal LA strain (22.85%+/-5.06 vs. 26.82%+/-5.15; p=0.008 in univariate
      analysis and p=0.026 in multivariate analysis) and global LV longitudinal strain
      (-13.55%+/-1.82 vs. -16.11%+/-1.33; p<0.001 in univariate analysis and p<0.001 in
      multivariate analysis), which was not observed with LA area tracking (p=0.412) or
      LV global circumferential strain (p=0.879), global radial strain (p=0.058), area
      tracking (p=0.092) or twist (p=0.992). CONCLUSION: LA and LV global longitudinal
      strain is significantly decreased in patients with DM1, which may be an early
      marker of subclinical dysfunction in these patients.

PMID- 29650435
TI  - Relationship between oxidative stress and muscle mass loss in early
      postmenopause: an exploratory study.
AB  - BACKGROUND: Endocrine changes due to menopause have been associated to oxidative
      stress and muscle mass loss. The study objective was to determine the
      relationship between both variables in early postmenopause. MATERIAL AND METHODS:
      An exploratory, cross-sectional study was conducted in 107 pre- and
      postmenopausal women (aged 40-57 years). Levels of serum lipid peroxides and uric
      acid and enzymes superoxide dismutase and glutathione peroxidase, as well as
      total plasma antioxidant capacity were measured as oxidative stress markers.
      Muscle mass using bioelectrical impedance and muscle strength using dynamometry
      were also measured. Muscle mass, skeletal muscle index, fat-free mass, and body
      mass index were calculated. RESULTS: More than 90% of participants were diagnosed
      with overweight or obesity. Postmenopausal women had lower values of muscle mass
      and strength markers, with a negative correlation between lipid peroxide level
      and skeletal muscle index (r= -0.326, p<.05), and a positive correlation between
      uric acid and skeletal muscle index (r=0.295, p<.05). A multivariate model
      including oxidative stress markers, age, and waist circumference showed lipid
      peroxide level to be the main contributor to explain the decrease in skeletal
      muscle mass in postmenopause, since for every 0.1MUmol/l increase in lipid
      peroxide level, skeletal muscle index decreases by 3.03 units. CONCLUSION: Our
      findings suggest an association between increased oxidative stress and muscle
      mass loss in early postmenopause.

PMID- 29650436
TI  - Iodine nutrition status and prevalence of abnormal TSH levels in schoolchildren
      aged 6-7 years in the autonomous community of the Basque Country.
AB  - INTRODUCTION: An epidemiological study conducted between 1988 and 1992 showed
      iodine deficiency and endemic goiter in the schoolchildren of the autonomous
      community of the Basque Country. OBJECTIVES: 1) To ascertain the iodine nutrition
      status of schoolchildren aged 6-7 years, and 2) to estimate the prevalence of
      abnormal TSH levels in capillary blood. POPULATION AND METHODS: The study was
      conducted on 497 schoolchildren selected by random sampling. Median urinary
      iodine concentration (mUIC) was used to assess iodine nutritional status, and the
      reference interval derived from the study population was used to estimate the
      prevalence of abnormal TSH levels. RESULTS: The mUIC (P25-P75) was 140 (82-217)
      MUg/L. A higher value was found in those who used iodized salt at home than in
      those who did not (146 [85-222] versus 126 MUg/L [73-198], P<0.05). It was also
      higher in those who consumed 2 or more daily servings of milk and yogurt than in
      those taking less than 2 servings (146 [87-225] versus 110 MUg/L [66-160],
      P<0.0001). Abnormal TSH levels were found in 2% of children. There was no
      correlation between TSH levels in capillary blood and urinary iodine
      concentrations (R=0.082; P=0.076). DISCUSSION AND CONCLUSIONS: Schoolchildren
      aged 6-7 years of the autonomous community of the Basque Country have an adequate
      iodine nutrition status. Use of iodized salt at home and daily consumption of
      milk and yogurt were associated to the highest UICs.

PMID- 29650437
TI  - PPI use and oesophageal cancer: What if the results are true?

PMID- 29650438
TI  - Hepatitis E virus infection mimicking acute graft rejection in a liver transplant
      recipient.
AB  - INTRODUCTION: In liver transplant (LT) patients, hepatitis E virus (HEV) can lead
      to acute liver failure, chronic hepatitis and graft cirrhosis. Few data on graft
      rejection associated with HEV are available and are subject to discussion. CASE
      REPORT: Here we report the case of a 58-year-old male patient who underwent LT in
      July 2015 for cirrhosis due to NASH and chronic alcohol intake complicated by
      hepatocellular carcinoma. LT was performed with a deceased donor isogroup and a
      mismatch CMV (donor+ and recipient-). HEV serology was negative before LT. In
      February 2016, we noted abnormal liver function, with increased transaminases and
      cholestasis parameters, without functional complaints. The patient was
      immunosuppressed by tacrolimus (4mg) and everolimus (2mg). Abdominal ultrasound
      was normal and liver biopsy showed signs of acute rejection (Banff score 6/9). We
      dispensed 500mg of methylprednisolone before obtaining positive serological
      results for HEV genotype 3 infection. Ribavirin (1,200mg per day) for 3 months
      was started, leading to rapid improvement in liver tests. Viral load became
      negative one month later. To date, the patient is under LP 5mg tacrolimus with
      normal liver tests. CONCLUSION: We describe a case of HEV genotype 3 infection
      mimicking acute cellular rejection, with a favorable outcome due to ribavirin
      treatment. As intensive immunosuppressive therapy administered for graft
      rejection may promote viral replication and worsen liver damage, potential HEV
      infection must be considered in cases of pathological signs of acute cellular
      rejection, in order to avoid chronic graft hepatitis, cirrhosis and liver
      decompensation.

PMID- 29650439
TI  - Aggressive hepatocellular carcinoma occurring during direct antiviral therapy.

PMID- 29650440
TI  - The effectiveness of Lactobacillus reuteri DSM 17938 as an adjunct to macrogol in
      the treatment of functional constipation in children. A randomized, double-blind,
      placebo-controlled, multicentre trial.
AB  - OBJECTIVE: Constipation is one of the most common problems among children, with a
      prevalence ranging from 7 to 30%. It is treated with defecation training and
      laxative medications. However, many patients do not respond to the standard
      therapy. There is, therefore, an increasing interest in probiotics for the
      treatment of functional constipation. STUDY DESIGN: The aim of this study was to
      assess the effectiveness of Lactobacillus reuteri DSM 17938 as an adjunct to
      macrogol in the treatment of functional, intractable constipation in children. A
      double-blind, placebo-controlled, randomized, multicentre trial involved a group
      of 129 children with functional constipation who were treated with a poor effect
      for at least two months prior to the study. Patients were randomly assigned to
      one of the two groups: 1. L. reuteri DSM 17938 and macrogol or 2. macrogol and
      matching placebo for 8 weeks. RESULTS: 121 patients completed the study. Almost
      all patients (119/129) increased their bowel movements in both groups (59 vs 60,
      ns.) and there was no statistically significant difference in the number of bowel
      movements per week in week 8 between the study and the placebo group (7.5+/-3.3
      vs 6.9+/-2.5, respectively). Additionally, there were no significant differences
      between groups in the numbers of patients complaining of pain during defecation
      (13/47 vs 8/53), abdominal pain (19/41 vs 25/36), withholding stools (15/45 vs
      13/48), passing hard stools (7/53 vs 3/58) or large stools (14/46 vs 12/49), and
      faecal incontinence (17/43 vs 11/50). CONCLUSION: L. reuteri DSM 17938
      supplementation as an additional therapy to macrogol did not have any beneficial
      effect on the treatment of functional constipation in children aged 3-7 years.

PMID- 29650441
TI  - Clinical implications of TERT promoter mutation on IDH mutation and MGMT promoter
      methylation in diffuse gliomas.
AB  - IDH mutation and MGMT promoter methylation are reliable prognostic and predictive
      biomarkers in grade II-IV diffuse gliomas. Recurrent mutations in the promoter
      region of the telomerase reverse transcriptase (TERTp) gene have also been found
      in diffuse gliomas. However, the prognostic and predictive effects of TERTp
      mutation on IDH or MGMT status are largely unknown. IDH1/2 and TERTp mutations,
      as well as MGMT methylation statuses, were examined via peptide nucleic acid
      mediated PCR clamping and MGMT methylation-specific PCR in 67 paraffinized tumor
      samples, respectively. TERTp mutation was associated with older patients (>=60
      years) and frontally located gliomas. Old age, frontal location, and grade IV
      were found to be predictive factors of TERTp mutation. TERTp mutation resulted in
      poor prognosis in overall diffuse gliomas. TERTp mutation was not correlated with
      overall survival (OS) or progression-free survival (PFS) in the diffuse gliomas.
      However, TERTp mutations, in combination with MGMT methylation or IDH mutation,
      showed that there were statistical significant survival differences between MGMT
      unmethylated/TERTp-mutated and MGMT-unmethylated/TERTp-wildtype subgroups in
      grade II gliomas. There was a statistical significant survival difference of OS
      between IDH-wildtype/TERTp-mutated and IDH-mutated/TERTp-mutated subgroups in
      grade III gliomas. No significant associations between survival and MGMT/TERTp or
      IDH/TERTp status were found in grade IV gliomas. In conclusion, the combination
      of TERTp with IDH or MGMT status may be a prognostic indicator depending on
      grades.

PMID- 29650442
TI  - Phenotypic and genotypic differences in colorectal carcinoma among Caucasians,
      Asians, and Hispanics lack statistical significance.
AB  - Colorectal carcinoma (CRC) has been shown to have both genetic and environmental
      factors that can promote carcinoma development. Previous studies have found
      ethnic differences in the distribution of molecular phenotypes of CRC. Very
      little specific data exist regarding Hispanic CRC, and these data primarily focus
      on epidemiology or location of carcinoma. Our retrospective study analyzed 562
      Caucasian, Asian, and Hispanic CRC patients at the UCI Medical Center from 2004
      to 2012. The results showed that there were no statistically significant
      differences with respect to mean age, gender or site of carcinoma among the three
      ethnic groups. There were no statistically significant differences among the
      three ethnicities with respect to rates of MSI, mutated BRAF, and mutated KRAS.
      The Caucasian group had a non-significant higher rate of MSI (15%) and BRAF
      mutation (12%) than the Asian and Hispanic groups. Hispanics had a non
      significant higher rate of KRAS mutation (59%) than Caucasians (38%) and Asians
      (37%). The results of this study demonstrated a higher rate of MSI and BRAF
      mutation in the Caucasian group and a higher rate of KRAS mutation in the
      Hispanic group, however differences were not statistically significant.

PMID- 29650443
TI  - Investigation of miR-136-5p key target genes and pathways in lung squamous cell
      cancer based on TCGA database and bioinformatics analysis.
AB  - BACKGROUND: Lung squamous cell cancer (LUSC) is a common but challenging
      malignancy. It is important to illuminate the molecular mechanism of LUSC. Thus,
      we aim to explore the molecular mechanism of miR-136-5p in relation to LUSC.
      METHODS: We used the Cancer Genome Atlas (TCGA) database to investigate the
      expression of miR-136-5p in relation to LUSC. Then, we identified the possible
      miR-136-5p target genes through intersection of the predicted miR-136-5p target
      genes and LUSC upregulated genes from TCGA. Bioinformatics analysis was performed
      to determine the key miR-136-5p targets and pathways associated with LUSC.
      Finally, the expression of hub genes, correlation between miR-136-5p and hub
      genes, and expected significance of hub genes were evaluated via the TCGA and
      Genotype-Tissue Expression (GTEx) project. RESULTS: MiR-136-5p was significantly
      downregulated in LUSC patients. Glucuronidation, glucuronosyltransferase, and the
      retinoic acid metabolic process were the most enriched metabolic interactions in
      LUSC patients. Ascorbate and aldarate metabolism, pentose and glucuronate
      interconversions, and retinol metabolism were identified as crucial pathways.
      Seven hub genes (UGT1A1, UGT1A3, UGT1A6, UGT1A7, UGT1A10, SRD5A1, and ADH7) were
      found to be upregulated, and UGT1A1, UGT1A3, UGT1A6, UGT1A7, and ADH7 were
      negatively correlated with miR-136-5p. UGT1A7 and ADH7 were the most
      significantly involved miR-136-5p target genes, and high expression of these
      genes was correlated with better overall survival and disease-free survival of
      LUSC patients. CONCLUSIONS: Downregulated miR-136-5p may target UGT1A7 and ADH7
      and participate in ascorbate and aldarate metabolism, pentose and glucuronate
      interconversions, and retinol metabolism. High expression of UGT1A7 and ADH7 may
      indicate better prognosis of LUSC patients.

PMID- 29650444
TI  - Reviewing state-mandated training requirements for naloxone-dispensing
      pharmacists.
AB  - BACKGROUND: Expanding access to naloxone is crucial for mitigating the public
      health epidemic of opioid overdose deaths in America. Pharmacists now have
      greater independent authority to dispense naloxone to the public due to a wave of
      enhanced pharmacy naloxone access laws. It is unknown to what extent pharmacists
      are required to receive specialized training to serve in this capacity.
      OBJECTIVES: The goal of this study was to review naloxone training mandates from
      states with enhanced pharmacy naloxone access laws. METHODS: Structured internet
      searches were completed using publicly available legislative, regulatory, and
      administrative records to identify the type of enhanced pharmacy naloxone access
      law and the presence and characteristics of a pharmacist naloxone training
      mandate in each state. RESULTS: As of November 22, 2017, all 50 states have
      implemented an enhanced pharmacy naloxone access law. Only 19 states mandated
      targeted naloxone education before pharmacists engaged in independent naloxone
      dispensing/prescribing activities. CONCLUSIONS: A lack of standardized naloxone
      training requirements for naloxone-dispensing pharmacists may affect the rate of
      adoption of enhanced pharmacy naloxone dispensing practices at community
      pharmacies and suboptimal education of patients at risk of opioid overdose.
      Ensuring pharmacists' preparedness to serve as naloxone providers is necessary to
      meaningfully prevent opioid overdose deaths in their communities.

PMID- 29650445
TI  - High-intensity Interval Training Dosage for Heart Failure and Coronary Artery
      Disease Cardiac Rehabilitation. A Systematic Review and Meta-analysis.
AB  - INTRODUCTION AND OBJECTIVES: High-interval intensity training (HIT) has been
      suggested to improve peak VO2 in cardiac rehabilitation programs. However, the
      optimal HIT protocol is unknown. The objective of this study was to identify the
      most effective doses of HIT to optimize peak VO2 in coronary artery disease (CAD)
      and heart failure (HF) patients. METHODS: A search was conducted in 6 databases
      (MEDLINE, Web of Science, LILACS, CINAHL, Academic Search Complete, and
      SportDiscus). Studies using a HIT protocol in CAD or HF patients and measuring
      peak VO2 were included. The PEDro Scale and Cochrane Collaboration tools were
      used. RESULTS: Analyses reported significant improvements in peak VO2 after HIT
      in both diseases (P = .000001), with a higher increase in HF patients (P = .03).
      Nevertheless, in HF patients, there were no improvements when the intensity
      recovery was <= 40% of peak VO2 (P = .19) and the frequency of training was <= 2
      d/wk (P = .07). There were significant differences regarding duration in CAD
      patients, with greater improvements in peak VO2 when the duration was < 12 weeks
      (P = .05). In HF, programs lasting < 12 weeks did not significantly improve peak
      VO2 (P = .1). CONCLUSIONS: The HIT is an effective method for improving peak VO2
      in HF and CAD, with a significantly greater increase in HF patients. The recovery
      intervals should be active and be between 40% and 60% of peak VO2 in HF patients.
      Training frequency should be >= 2 d/wk for CAD patients and >= 3 d/wk for HF
      patients.

PMID- 29650446
TI  - Prognostic Impact and Predictors of Ejection Fraction Recovery in Patients With
      Alcoholic Cardiomyopathy.
AB  - INTRODUCTION AND OBJECTIVES: Recovery of left ventricular ejection fraction
      (LVEF) has been described in alcoholic cardiomyopathy (ACM) after a period of
      alcohol withdrawal. Nevertheless, the prognostic impact of LVEF recovery in ACM
      and its determinants have not been studied. We sought to define the role of LVEF
      improvement in the long-term outcome of ACM and to identify predictors of LVEF
      recovery in these patients. METHODS: We evaluated 101 ACM patients during a
      median follow-up period of 82 months [interquartile range 36-134]. RESULTS: At
      latest follow-up, 42 patients (42%) showed substantial LVEF recovery defined as
      an absolute increase in LVEF >= 10% to a final value of >= 40%. Patients who
      recovered LVEF had better outcomes than patients who did not (heart transplant or
      cardiovascular death 1% vs 30%; P <.001). A QRS with <120ms (OR, 6.68; 95%CI,
      2.30-19.41), beta-blocker therapy (OR, 3.01; 95%CI, 1.09-8.28), and the absence
      of diuretics (OR, 3.35; 95%CI, 1.08-10.42) predicted LVEF recovery in
      multivariate analysis. Although alcohol cessation did not predict LVEF recovery,
      none of the patients (n=6) who persisted with heavy alcohol consumption recovered
      LVEF. The rate of patients who recovered LVEF did not differ between abstainers
      and moderate drinkers (44% vs 45%; P=.9). CONCLUSIONS: The LVEF recovery is
      associated with an excellent prognosis in ACM. Beta-blocker treatment, QRS <120ms
      and absence of diuretics are independent predictors of LVEF recovery. LVEF
      recovery is similar in moderate drinkers and abstainers.

PMID- 29650447
TI  - The Clinical Decision: A Clue to Health Services Outcomes Everywhere.

PMID- 29650448
TI  - Nanotechnology Applied to Preserve Extracelular Matrix as Teranostic Tool in
      Acute Myocardial Infarction.

PMID- 29650449
TI  - Cardiac Sympathetic Innervation and Appropriate Therapies in Patients With an
      Implantable Cardioverter-Defibrillator in Primary Prevention.

PMID- 29650450
TI  - Familial Brugada Syndrome Associated With a Complete Deletion of the SCN5A and
      SCN10A Genes.

PMID- 29650451
TI  - HIV incidence in western Kenya during scale-up of antiretroviral therapy and
      voluntary medical male circumcision: a population-based cohort analysis.
AB  - BACKGROUND: In Kenya, coverage of antiretroviral therapy (ART) among people with
      HIV infection has increased from 7% in 2006, to 57% in 2016; and, in western
      Kenya, coverage of voluntary medical male circumcision (VMMC) increased from 45%
      in 2008, to 72% in 2014. We investigated trends in HIV prevalence and incidence
      in a high burden area in western Kenya in 2011-16. METHODS: In 2011, 2012, and
      2016, population-based surveys were done via a health and demographic
      surveillance system and home-based counselling and testing in Gem, Siaya County,
      Kenya, including 28 688, 17 021, and 16 772 individuals aged 15-64 years. Data on
      demographic variables, self-reported HIV status, and risk factors were collected.
      Rapid HIV testing was offered to survey participants. Participants were tracked
      between surveys by use of health and demographic surveillance system
      identification numbers. HIV prevalence was calculated as a proportion, and HIV
      incidence was expressed as number of new infections per 1000 person-years of
      follow-up. FINDINGS: HIV prevalence was stable in participants aged 15-64 years:
      15% (4300/28 532) in 2011, 12% (2051/16 875) in 2012, and 15% (2312/15 626) in
      2016. Crude prevalences in participants aged 15-34 years were 11% (1893/17 197)
      in 2011, 10% (1015/10 118) in 2012, and 9% (848/9125) in 2016; adjusted for age
      and sex these prevalences were 11%, 9%, and 8%. 12 606 (41%) of the 30 520 non
      HIV-infected individuals enrolled were seen again in at least one more survey
      round, and were included in the analysis of HIV incidence. HIV incidence was 11.1
      (95% CI 9.1-13.1) per 1000 person-years from 2011 to 2012, and 5.7 (4.6-6.9) per
      1000 person-years from 2012 to 2016. INTERPRETATION: With increasing coverage of
      ART and VMMC, HIV incidence declined substantially in Siaya County between 2011
      and 2016. VMMC, but not ART, was suggested to have a direct protective effect,
      presumably because ART tended to be given to individuals with advanced HIV
      infection. HIV incidence is still high and not close to the elimination target of
      one per 1000 person-years. The effect of further scale-up of ART and VMMC needs
      to be monitored. FUNDING: Data were collected under Cooperative Agreements with
      the US Centers for Disease Control and Prevention, with funding from the
      President's Emergency Fund for AIDS Relief.

PMID- 29650452
TI  - HIV incidence and scale-up of prevention in western Kenya.

PMID- 29650453
TI  - Feasibility of real-time intraoperative fluorescence imaging of dural sinus
      thrombosis.
AB  - Dural sinus thrombosis is a well-recognized and potentially serious complication
      following lateral skull base surgery. Methods of diagnosis are limited to post
      operative computerized tomography scans or magnetic resonance venography. There
      are currently no reports of an intraoperative technique used to detect dural
      sinus thrombosis. Here, we describe the case of a 62-year-old woman who underwent
      translabyrinthine resection of a right vestibular schwannoma with no evidence of
      sinus thrombosis on pre-operative scans. Following tumor resection, patency of
      the sigmoid sinus was assessed intraoperatively using indocyanine green (ICG)
      videography which revealed a lack of flow in the right sigmoid sinus.
      Postoperative CT scan confirmed thrombosis of the right sigmoid sinus. We present
      the first report of real-time intraoperative diagnosis of sigmoid sinus
      thrombosis during removal of a vestibular schwannoma. ICG videography may be used
      for intraoperative visualization of dural sinus integrity and patency during
      prolonged or technically challenging microsurgical procedures. This technique may
      enable periodic monitoring and early identification of filling defects which can
      guide further intraoperative strategies and postoperative monitoring.

PMID- 29650454
TI  - Adrenal metastasis as presentation of hepatocellular carcinoma.

PMID- 29650455
TI  - Foreword: Aerodigestive Disorders: Part II.

PMID- 29650456
TI  - [Androgens and cardiovascular risk: A series of case report in the French and
      Canadian pharmacovigilance databases].
AB  - INTRODUCTION: Age-related androgenic deficiency (DALA) is a pathology that is
      increasingly cited in recent publications. The cardiovascular risk of
      testosterone is debated: present for the FDA, absent for the European Medicines
      Agency in 2015. Our objective was to analyze the association between androgens
      and vascular pathologies in adverse reactions reported in pharmacovigilance
      databases. MATERIAL AND METHOD: We conducted a retrospective case series study of
      the French and Canadian pharmacovigilance databases for the period 2005-2015.
      Cases were defined as the association of the occurrence of a cardiovascular event
      (myocardial infarction or stroke) and the presence of testosterone in the
      treatment of patients. RESULTS: Of the 10 years analyzed, 12 French cases and 6
      Canadian cases (representing 13 MIs and 5 strokes) were recorded in men aged 55
      years on average. All were doubtful: differential diagnoses were possible (2.4
      confounding conditions on average per patient) and overall cardiovascular risk
      was high for the majority of cases. CONCLUSION: Our study shows a very low report
      of cardiovascular effects under testosterone, all doubtful. Pending further
      studies, it seems reasonable to consider the cardiovascular risk of patients who
      are candidates for hormone therapy for age-related androgen deficiency. LEVEL OF
      EVIDENCE: 3.

PMID- 29650457
TI  - [Non-palpable testicular tumors in adults: A management based on imaging? Issue
      from the French Urologic Association Genital Cancer committee's edit].
AB  - BACKGROUND: Help in management of non-palpable testicular tumors. French Urologic
      Association Genital cancer committee's Edit. OBJECTIVES: To review their
      characterization at imaging findings of non-palpable testicular tumors.
      DOCUMENTARY SOURCES: Literature review (PubMed, Medline) of urological and
      radiological studies dealing with testicular tumors using keywords: non
      palpable/incidental testicular tumors; color Doppler ultrasound; US elastography;
      magnetic resonance imaging; contrast enhanced sonography; partial surgery.
      RESULTS: Color Doppler is the basic exam. The size, the presence of
      microlithts/microlithiasis/macrocalcifications, the vascular architecture are
      major semiological findings to suggest the benign or the malignant nature of the
      lesion. Other techniques like multiparametric MRI, contrast-enhanced sonography,
      sonographic elastography are still in evaluation. The frequency of benign tumors
      such as Leydig cell tumors lead to preservation management, through improved
      characterization, monitoring or tumorectomy. LIMITS: Non-randomized study - a
      very few prospective studies. CONCLUSION: The era of total orchiectomy for any
      uncertain testicular lesion is over. We try the challenge of characterization,
      and define management's algorithms based on the suspected nature of the tumors.

PMID- 29650458
TI  - Matching algorithms for assigning orthologs after genome duplication events.
AB  - In this paper, we introduce and analyze two graph-based models for assigning
      orthologs in the presence of whole-genome duplications, using similarity
      information between pairs of genes. The common feature of our two models is that
      genes of the first genome may be assigned two orthologs from the second genome,
      which has undergone a whole-genome duplication. Additionally, our models
      incorporate the new notion of duplication bonus, a parameter that reflects how
      assigning two orthologs to a given gene should be rewarded or penalized. Our work
      is mainly focused on developing exact and reasonably time-consuming algorithms
      for these two models: we show that the first one is polynomial-time solvable,
      while the second is NP-hard. For the latter, we thus design two fixed-parameter
      algorithms, i.e. exact algorithms whose running times are exponential only with
      respect to a small and well-chosen input parameter. Finally, for both models, we
      evaluate our algorithms on pairs of plant genomes. Our experiments show that the
      NP-hard model yields a better cluster quality at the cost of lower coverage, due
      to the fact that our instances cannot be completely solved by our algorithms.
      However, our results are altogether encouraging and show that our methods yield
      biologically significant predictions of orthologs when the duplication bonus
      value is properly chosen.

PMID- 29650459
TI  - Examining the Feasibility of Healthy Minimum Stocking Standards for Small Food
      Stores.
AB  - OBJECTIVE: In response to recent national efforts to increase the availability of
      healthy food in small stores, we sought to understand the extent to which small
      food stores could implement the newly published Healthy Small Store Minimum
      Stocking Recommendations and reflect on the new US Department of Agriculture Food
      and Nutrition Service's final rule for stocking of staple foods for Supplemental
      Nutrition Assistance Program-approved retailers. DESIGN: We collected qualitative
      and quantitative data from 57 small stores in four states (Arizona, Delaware,
      Minnesota, and North Carolina) that accepted Supplemental Nutrition Assistance
      Program but not Special Supplemental Nutrition Assistance Program for Women,
      Infants, and Children benefits. Data from semistructured, in-depth interviews
      with managers/owners were transcribed, coded, and analyzed. We collected
      quantitative store inventory data onsite and later performed descriptive
      analyses. RESULTS: Store interviews revealed a reluctant willingness to stock
      healthy food and meet new recommendations. No stores met recommended fruit and
      vegetable stocking, although 79% carried at least one qualifying fruit and 74%
      carried at least one qualifying vegetable. Few stores met requirements for other
      food categories (ie, whole grains and low-fat dairy) with the exception of lean
      proteins, where stores carrying nuts or nut butter were more likely to meet the
      protein recommendation. Water and 100% juice were widely available and 68% met
      basic healthy beverage criteria. CONCLUSIONS: In contrast to the inventory
      observed, most owners believed store stock met basic recommendations. Further,
      findings indicate that small stores are capable of stocking healthy products;
      however, technical and infrastructure support, as well as incentives, would
      facilitate shifts from staple to healthier staple foods. Retailers may need
      support to understand healthier product criteria and to drive consumer demand for
      new products.

PMID- 29650460
TI  - How does an animal behave like a plant? Physiological and molecular adaptations
      of zooxanthellae and their hosts to symbiosis.
AB  - Cnidarians (corals and sea anemones) harbouring photosynthetic microalgae derive
      several benefits from their association. To allow this association, numerous
      symbiotic-dependent adaptations in both partners, resulting from evolutionary
      pressures, have been selected. The dinoflagellate symbionts (zooxanthellae) are
      located inside a vesicle in the cnidarian host cell and are therefore exposed to
      a very different environment compared to the free-living state of these
      microalgae in terms of ion concentration and carbon content and speciation. In
      addition, this intracellular localization imposes that they rely completely upon
      the host for their nutrient supply (nitrogen, CO2). Symbiotic-dependent
      adaptations imposed to the animal host by phototrophic symbiosis are more
      relevant to photosynthetic organisms than to metazoans: indeed, the cnidarian
      host often harbours diurnal changes of morphology to adapt itself to the amount
      of light and possesses carbon-concentrating mechanisms, antioxidative defences
      and UV sunscreens similar to that present in phototrophs. These adaptations and
      the contrasting fragility of the association are discussed from both ecological
      and evolutionary points of view.

PMID- 29650461
TI  - Towards designing a synthetic antituberculosis vaccine: The Rv3587c peptide
      inhibits mycobacterial entry to host cells.
AB  - Mycobacterium tuberculosis is considered one of the most successful pathogens in
      the history of mankind, having caused 1.7 million deaths in 2016. The amount of
      resistant and extensively resistant strains has increased; BCG has been the only
      vaccine to be produced in more than 100 years though it is still unable to
      prevent the disease's most disseminated form in adults; pulmonary tuberculosis.
      The search is thus still on-going for candidate antigens for an antituberculosis
      vaccine. This paper reports the use of a logical and rational methodology for
      finding such antigens, this time as peptides derived from the Rv3587c membrane
      protein. Bioinformatics tools were used for predicting mycobacterial surface
      location and Rv3587c protein structure whilst circular dichroism was used for
      determining its peptides' secondary structure. Receptor-ligand assays identified
      4 high activity binding peptides (HABPs) binding specifically to A549 alveolar
      epithelial cells and U937 monocyte-derived macrophages, covering the region
      between amino acids 116 and 193. Their capability for inhibiting Mtb H37Rv
      invasion was evaluated. The recognition of antibodies from individuals suffering
      active and latent tuberculosis and from healthy individuals was observed in HABPs
      capable of avoiding mycobacterial entry to host cells. The results showed that 8
      HABPs inhibited such invasion, two of them being common for both cell lines:
      39265 (155VLAAYVYSLDNKRLWSNLDT173) and 39266 (174APSNETLVKTFSPGEQVTTY192).
      Peptide 39265 was the least recognised by antibodies from the individuals' sera
      evaluated in each group. According to the model proposed by FIDIC regarding
      synthetic vaccine development, peptide 39265 has become a candidate antigen for
      an antituberculosis vaccine.

PMID- 29650462
TI  - Thioamide substitution to probe the hydroxyproline recognition of VHL ligands.
AB  - Thioamide substitution influences hydrogen bond and n -> pi* interactions
      involved in the conformational stability of protein secondary structures and
      oligopeptides. Hydroxyproline is the key recognition element of small molecules
      targeting the von Hippel-Lindau (VHL) E3 ligase, which are of interest as probes
      of hypoxia signaling and ligands for PROTAC conjugation. We hypothesized that VHL
      ligands could be a privileged model system to evaluate the contribution of these
      interactions to protein:ligand complex formation. Herein we report the synthesis
      of VHL ligands bearing thioamide substitutions at the central hydroxyproline
      moiety, and characterize their binding by fluorescence polarization, isothermal
      titration calorimetry, X-ray crystallography and molecular modeling. In spite of
      a conserved binding mode, the substitution pattern had a pronounced impact on the
      ligand affinities. Together the results underscore the role of hydrogen bond and
      n -> pi* interactions in fine tuning hydroxyproline recognition by VHL.

PMID- 29650463
TI  - A new class of pyrazolo[5,1-c][1,2,4]triazines as gamma-aminobutyric type A
      (GABAA) receptor subtype ligand: synthesis and pharmacological evaluation.
AB  - A comparison between compounds with pyrazolo[1,5-a]pyrimidine structure (series 4
      6) and pyrazolo[5,1-c][1,2,4]triazine core (series 9) as ligands at GABAA
      receptor subtype, was evaluated. Moreover, for pyrazolotriazine derivatives
      having binding recognition, the interaction on recombinant rat alpha(1-3,5) GABAA
      receptor subtypes, was performed. Among these latter, emerge compounds 9c, 9k,
      9l, 9m and 9n as alpha1-selective and 9h as alpha2-selective ligands.

PMID- 29650464
TI  - Clioquinol, an alternative antimicrobial agent against common pathogenic microbe.
AB  - Skin and soft tissue infections (SSTIs) are very common in dermatology and the
      use of antimicrobial formulations are important in treating these diseases. With
      the increasing of drug-resistant strains, researchers need to find ways to
      enhance the effectiveness and/or reduce the drug resistance. Clioquinol was one
      of antiseptics that can inactivate microbes. It was lack of data of antimicrobial
      activity; meanwhile it was infrequently used in infection. In order to research
      the antimicrobial spectrum and activity of topical 3% clioquinol cream among
      common pathogenic microorganisms compared with other common topical
      pharmaceuticals, we used modified agar diffusion assay to judge drug
      susceptibility and compared with broth microdilution assay. Thirty strains of
      pathogenic fungi belonging to 14 species and 5 strains of pathogenic bacterium
      belonging to 4 species from clinic or standard strains were enrolled into the
      experiment. The inhibition zone around 3% clioquinol cream for all experiment
      isolates was observed. It could inhibit the growth of most fungal species with
      different strength, but the antibacterial activity was weak. For Candida
      tropicalis, Candida guilliermondii, Aspergillus terreus, Fusarium solani and
      Trichoderma harzianum, the inhibition zone was biggest among all the tested
      drugs. The antifungal activity for Dermatophytes and Candida albicans was
      moderate. Two assays had a degree of consistency. Based on results above, we
      identified the antifungal spectrum of 3% clioquinol cream was broad. The
      antimicrobial strength of 3% clioquinol cream depended on the species but it can
      act on most of the species.

PMID- 29650465
TI  - Response to letter to editor regarding: EB_2017_222_R1 frequency and predictors
      of psychological distress after a diagnosis of epilepsy: A community-based study:
      Methodological issues.

PMID- 29650466
TI  - Prodrome in epilepsy.
AB  - BACKGROUND: Prodromal symptoms (PS) of epileptic seizures are clinically well
      recognized but relatively little researched. The purpose of this review was to
      examine the evidence in the literature for the existence of prodrome and the
      reported frequency and nature of prodromal characteristics. METHODS: We performed
      a PubMed review of the clinical characteristics, frequency, and duration of PS in
      papers published between 2007 and 2017. We also reviewed findings from
      prospective studies into the predictive performance of prodrome. In a second
      analysis, we reviewed studies reporting a single symptom/sign of prodrome.
      RESULTS: In 8 studies reporting on the prevalence of prodrome, we found a mean
      frequency of 21.9%. The most frequent symptoms were "funny feeling" (10.4%),
      confusion (9.0%), anxiety (8.6%), and irritability (7.7%), but other features
      were also reported. The duration of prodrome was typically between 10min and
      3days, with most prodromes lasting for between 30min and 24h. In studies that
      reported a single prodromal symptom/sign, headache was the most frequent: 8% with
      a range of between 1.2 and 30%. CONCLUSIONS: Prodromes are characterized by a
      broad spectrum of preictal symptoms that may be experienced for a duration of
      between 10min and several days, which usually persist until seizure onset.
      Opinion is divided on their precise nature and value as predictors of seizures. A
      greater understanding of prodromes might offer insights into the preictal period
      and hold promise for new seizure management therapies.

PMID- 29650468
TI  - Exploring Bacteroidetes: Metabolic key points and immunological tricks of our gut
      commensals.
AB  - Bacteroidetes are the largest phylum of Gram-negative bacteria inhabiting our
      gastrointestinal tract and are considered the leading players of the healthy
      state and sophisticated homeostasis safeguarded by gut microbiota. Furthermore,
      specific roles have been attributed to some Bacteroidetes genera in the
      development of immune dysregulation, systemic disease such as metabolic syndrome
      and also neurological disorders. Glycoproteins secretion, short fatty acids
      imbalance, toxins production and molecular mimicry are only a part of the
      functions exerted by these commensals interacting with the host. The aim of this
      review is to summarize the current knowledge on the recognized role of
      Bacteroidetes in physiological functions and pathological networks in order to
      define the needs for future research and clarify the potential role for targeted
      microbial therapies.

PMID- 29650467
TI  - Chemically Modified Cpf1-CRISPR RNAs Mediate Efficient Genome Editing in
      Mammalian Cells.
AB  - CRISPR-based gene editing is a powerful technology for engineering mammalian
      genomes. It holds the potential as a therapeutic, although much-needed in vivo
      delivery systems have yet to be established. Here, using the Cpf1-crRNA (CRISPR
      RNA) crystal structure as a guide, we synthesized a series of systematically
      truncated and chemically modified crRNAs, and identify positions that are
      amenable to modification while retaining gene-editing activity. Modified crRNAs
      were designed with the same modifications that provide protection against
      nucleases and enable wide distribution in vivo. We show crRNAs with chemically
      modified terminal nucleotides are exonuclease resistant while retaining gene
      editing activity. Chemically modified or DNA-substituted nucleotides at select
      positions and up to 70% of the crRNA DNA specificity region are also well
      tolerated. In addition, gene-editing activity is maintained with phosphorothioate
      backbone substitutions in the crRNA DNA specificity region. Finally, we
      demonstrate that 42-mer synthetic crRNAs from the similar CRISPR-Cas9 system are
      taken up by cells, an attractive property for in vivo delivery. Our study is the
      first to show that chemically modified crRNAs of the CRISPR-Cpf1 system can
      functionally replace and mediate comparable gene editing to the natural crRNA,
      which holds the potential for enhancing both viral- and non-viral-mediated in
      vivo gene editing.

PMID- 29650470
TI  - Can the measurement of intravesical prostatic protrusion predict the response to
      medical treatment in patients with benign prostatic hyperplasia? Lights and
      shadows.

PMID- 29650469
TI  - Expanding the traditional role of optometry: Current practice patterns and
      attitudes to enhanced glaucoma services in Ireland.
AB  - PURPOSE: To investigate current diagnostic equipment availability and usage for
      glaucoma case-finding within community optometric practice, and to explore
      optometrists' attitudes towards an enhanced scope of clinical practice. METHODS:
      An anonymous survey was developed, validated, and distributed to all optometrists
      in Ireland. RESULTS: 199 optometrists (27% of registrants) responded to the
      survey. 87% had access to the traditional triad of tests necessary to conduct
      adequate glaucoma case finding. Standard automated perimetry was the most
      commonly absent (13%) of the three essential screening tests. 64% of respondents
      indicated that monocular direct ophthalmoscopy was their first choice technique
      for fundus examination. 47% of respondents had access to contact applanation
      tonometry, though just 14% used it as first choice during routine eye
      examinations. Among the 73 participants with access to both contact and non
      contact tonometry (NCT), 80.8%, used NCT preferentially. The significant majority
      (98%) indicated an interest in enhanced glaucoma services with 57% agreeing that
      postgraduate training was an essential prerequisite to any increase in scope of
      practice. CONCLUSION: Irish optometrists are well equipped with the traditional
      tests used in glaucoma detection. However, implementation of enhanced referral
      schemes or glaucoma monitoring or management services would require equipment
      upgrades and associated training in at least half of the surveyed practices.
      There is strong interest in furthering optometric professional development and
      expanding the traditional role boundaries of optometrists, incorporating further
      education as an essential prerequisite to an enhanced scope of practice.

PMID- 29650471
TI  - Validation of the Spanish version of the Bladder Pain/Interstitial Cystitis
      Symptom Score (BPIC-SS) questionnaire. A useful tool for the diagnosis of bladder
      pain syndrome.
AB  - OBJECTIVES: Validation of the Spanish version of the Bladder Pain/Interstitial
      Cystitis-Symptom Score (BPIC-SS) questionnaire to evaluate its utility for the
      diagnosis of Bladder Pain Syndrome (BPS) patients in the Female and Urodynamics
      Urology Functional Units in Spain. MATERIAL AND METHODS: The Spanish adaptation
      of the BPIC-SS questionnaire was evaluated in 243 BPS patients. EQ-5D-5L, Patient
      Perception of Bladder Condition (PPBC) and global impression questionnaire (CGI
      S) were collected. Consistency, test-retest reliability in patients without
      clinical changes at 15 days, criterion validity and sensitivity to change were
      assessed in BPS patients with clinical changes at 6 months. The cut-off point for
      discriminating BPS patients from other similar pathologies (Hyperactive Bladder
      or other urinary pathologies) was analysed using ROC curve. RESULTS: Mean (SD)
      BPIC-SS score (0-38) was 16.2 (12.0) points. Cronbach's alpha was 0.92 and
      intraclass coefficient correlation (ICC) was 0.82, ranging from 0.5-0.9 per item.
      Convergent validity determined a Spearman correlation of 0.63 with PPBC and -0.40
      with EQ-5D-5L Visual Analogue Scale (VAS) and the effect size obtained in
      patients who improved their clinical status was 1.9. A score greater than or
      equal to 12 points in the BPIC-SS has been established as the best cut-off point
      for the diagnosis of BPS (87.5% sensitivity and 91.9% specificity). CONCLUSIONS:
      The Spanish version of the BPIC-SS is a valid and reliable instrument for the
      diagnosis and follow-up of patients with BPS in Spain.

PMID- 29650472
TI  - Could exercise improve mental health and cognitive skills for surgeons and other
      healthcare professionals?
AB  - Workplace-related illness is common in the UK, and in healthcare more than five
      million working days over 10years have been lost as a result. Occupational stress
      is well known and can affect clinicians at any stage, yet many healthcare
      professionals continue to work with this or other psychological problems
      (including anxiety, chronic fatigue, and burnout) as they do not wish to let
      their colleagues down. Mental health issues might be dismissed, particularly in
      surgery, because there is a misconception that surgeons can cope better with
      stress than those working in other specialties, and are better protected from
      clinical burnout. The benefit of exercise on physical health is clear, but its
      role in the maintenance of good mental health and well-being should not be
      underestimated. As society adopts an increasingly sedentary lifestyle, exercise
      for many has a lower priority than other activities. In this article we give an
      overview of the mental health issues that might affect doctors and surgeons, and
      explore how exercise can benefit our well-being and clinical performance.

PMID- 29650473
TI  - Tetanus after a penetrating injury to the right globe: a case report.
AB  - A 24-year-old man attended the emergency department with a penetrating injury to
      the right globe after a road traffic accident. He later contracted tetanus for
      which he was given human tetanus immunoglobulin. Although it is rare, tetanus is
      life-threatening and a thorough immunisation history should be obtained before
      treatment of tetanus-prone injuries.

PMID- 29650474
TI  - Current trends in the medical management of osteoradionecrosis using triple
      therapy.
AB  - Recent guidelines from the National Institute for Health and Care Excellence
      (NICE) have suggested that the medical management of osteoradionecrosis (ORN) of
      the jaws should be used in clinical trials only, and some drugs and therapeutics
      committees have withdrawn funds for such prescriptions. With increased scrutiny
      on the use of these agents, the aims of this study were to ascertain current
      trends in the presentation and management of ORN, with particular focus on which
      agents are being used.

PMID- 29650475
TI  - Use of patient-reported outcome measures in oral and maxillofacial trauma
      surgery: a review.
AB  - In the UK, about one person/100/year sustains a facial injury, so trauma surgery
      accounts for a considerable part of the caseload in oral and maxillofacial
      surgery (OMFS). Patient-reported outcome measures (PROM) allow for patient
      centred assessment of postoperative outcomes, but to our knowledge, most research
      in OMFS trauma does not currently include them. To investigate their use, we
      searched Medline to find relevant studies that reported outcomes from inception
      in January 1879 to August 2016. Those not in the English language and those that
      did not report operations were excluded. We retrieved 416 articles, of which 21
      met the inclusion criteria (five randomised controlled trials and 16 cohort
      studies) yielding 16 outcome measures. Most of these had been devised by authors
      (eight studies), four studies reported use of the Geriatric Oral Health
      Assessment Index, and three the Nasal Obstruction Symptom Evaluation. Most were
      used in studies on mandibular surgery (n=13), followed by those on nasal and
      facial surgery (n=3 each). There is a great heterogeneity in the use of these
      assessments in OMF trauma. In view of their increasing importance compared with
      simpler objective measures that may not be relevant to the patients' own
      perception, more research is needed to establish which of them can be used to
      measure the QoL of patients treated for OMF trauma.

PMID- 29650476
TI  - Re: re: Retroseptal transconjunctival approach for fractures of the
      zygomaticomaxillary complex: a retrospective study.

PMID- 29650477
TI  - Determination of 24 personal care products in fish bile using hybrid solvent
      precipitation and dispersive solid phase extraction cleanup with ultrahigh
      performance liquid chromatography-tandem mass spectrometry and gas chromatography
      mass spectrometry.
AB  - Personal care products (PCPs) are ubiquitous in aquatic environments owing to the
      continuous discharge of domestic wastewater from highly urbanized regions. These
      PCPs can be adsorbed by fish and thereafter usually enter the bile of the fish
      through biliary excretion. In this study, a sensitive method based on a
      combination of hybrid solvent precipitation and dispersive solid phase extraction
      (d-SPE) purification was developed to simultaneously extract and detect 24 PCPs,
      namely, 16 biocides, 4 synthetic musks, and 4 benzotriazoles, from fish bile.
      Hybrid precipitation on solid phase extraction (SPE) tubes was applied to remove
      phospholipids and proteins, and a d-SPE procedure was used for further
      purification. The extraction solvents for the hybrid precipitation/SPE tubes and
      d-SPE materials were optimized. The method performance for bile samples both with
      and without enzyme hydrolysis using beta-glucuronidase/aryl-sulfatase were
      validated. The 24 PCPs in fish bile were spiked with standard concentrations of
      10 ng/mL, 20 ng/mL, 100 ng/mL, and 200 ng/mL to evaluate recoveries, which ranged
      from 70 to 120% for 16, 16, 22, and 21 analytes with hydrolysis, respectively,
      and 70-120% for 14, 15, 23, and 23 analytes without hydrolysis, respectively. The
      quantification limits for target PCPs were in the range 0.26-7.38 ng/mL
      [excluding musk xylene (MX) and musk ketone (MK)] and 0.20-9.48 ng/mL (excluding
      MX and MK) for bile samples with and without enzyme hydrolysis, respectively.
      After enzyme hydrolysis, 12 PCPs were detected in bile from fish collected from
      the Yangtze River, with a maximum detected concentration of 460 ng/mL, for
      triclosan (TCS). The hydrolysis reaction indicated that high percentages of
      glucuronide and sulfate metabolites for some PCPs, i.e. four parabens and TCS,
      existed in the bile.

PMID- 29650478
TI  - A strategy to improve the identification reliability of the chemical constituents
      by high-resolution mass spectrometry-based isomer structure prediction combined
      with a quantitative structure retention relationship analysis: Phthalide
      compounds in Chuanxiong as a test case.
AB  - High-resolution mass spectrometry (HRMS) provides a powerful tool for the rapid
      analysis and identification of compounds in herbs. However, the diversity and
      large differences in the content of the chemical constituents in herbal
      medicines, especially isomerisms, are a great challenge for mass spectrometry
      based structural identification. In the current study, a new strategy for the
      structural characterization of potential new phthalide compounds was proposed by
      isomer structure predictions combined with a quantitative structure-retention
      relationship (QSRR) analysis using phthalide compounds in Chuanxiong as an
      example. This strategy consists of three steps. First, the structures of
      phthalide compounds were reasonably predicted on the basis of the structure
      features and MS/MS fragmentation patterns: (1) the collected raw HRMS data were
      preliminarily screened by an in-house database; (2) the MS/MS fragmentation
      patterns of the analogous compounds were summarized; (3) the reported phthalide
      compounds were identified, and the structures of the isomers were reasonably
      predicted. Second, the QSRR model was established and verified using
      representative phthalide compound standards. Finally, the retention times of the
      predicted isomers were calculated by the QSRR model, and the structures of these
      peaks were rationally characterized by matching retention times of the detected
      chromatographic peaks and the predicted isomers. A multiple linear regression
      QSRR model in which 6 physicochemical variables were screened was built using 23
      phthalide standards. The retention times of the phthalide isomers in Chuanxiong
      were well predicted by the QSRR model combined with reasonable structure
      predictions (R2=0.955). A total of 81 peaks were detected from Chuanxiong and
      assigned to reasonable structures, and 26 potential new phthalide compounds were
      structurally characterized. This strategy can improve the identification
      efficiency and reliability of homologues in complex materials.

PMID- 29650479
TI  - Core-shell indium (III) sulfide@metal-organic framework nanocomposite as an
      adsorbent for the dispersive solid-phase extraction of nitro-polycyclic aromatic
      hydrocarbons.
AB  - A core-shell discoid shaped indium (III) sulfide@metal-organic framework (MIL
      125(Ti)) nanocomposite was synthesized by a solvothermal method and explored as
      an adsorbent material for dispersive solid-phase extraction (d-SPE). The as
      synthesized sorbent was characterized by scanning electron microscopy, energy
      dispersive spectroscopy, transmission electron microscopy, powder X-ray
      diffraction, N2 adsorption-desorption analysis, and Fourier transform infrared
      spectroscopy. The extraction performance was evaluated by the d-SPE of 16 nitro
      polycyclic aromatic hydrocarbons (NPAHs) from water samples. The analysis was
      carried out by gas chromatography (GC) coupled with triple quadruple mass
      spectrometer in negative chemical ionization (NCI) mode. The selected ion
      monitoring (SIM) was used in the quantification of the target NPAHs. Extraction
      factors affecting the d-SPE, including the ionic strength, extraction
      temperature, and extraction time were optimized by the response surface
      methodology. The developed d-SPE method showed good linear correlations from 10
      to 1000 ng L-1 (r > 0.99), low detection limits (2.9-83.0 ng L-1), satisfactory
      repeatability (relative standard deviation of <10%, n = 6), and acceptable
      recoveries (71.3%-112.2%) for water samples. The developed method was used for
      the food and environmental sample analysis. The results demonstrated that the
      method could be used for sample preparation of trace NPAHs in real samples.

PMID- 29650480
TI  - One-pot polymerization of monolith coated stir bar for high efficient sorptive
      extraction of perfluoroalkyl acids from environmental water samples followed by
      high performance liquid chromatography-electrospray tandem mass spectrometry
      detection.
AB  - In this work, poly(1-vinylimidazole-ethyleneglycol dimethacrylate) (poly(VI
      EDMA)) monolith coated stir bars were synthesized by one-pot polymerization, and
      they exhibited higher extraction efficiency and faster extraction dynamics for
      selected PFAAs than commercial ethylene glycol modified silicone (EG-silicone)
      and polydimethylsiloxane (PDMS) coated stir bars. Taking eleven PFAAs as target
      analytes, including C4-C12 perfluoroalkyl carboxylates (PFCAs) and C6, C8
      perfluoroalkane sulfonates (PFSAs), a method combining monolith-based stir bar
      sorptive extraction (SBSE) with high performance liquid chromatography (HPLC) -
      electrospray tandem mass spectrometry (ESI-MS/MS) was proposed for the
      determination of multiplex PFAAs in environmental water samples. Under the
      optimized conditions, low limits of detection (0.06-0.40 ng/L) and wide linear
      range (0.6-400 ng/L) were obtained for target PFAAs with. The developed method
      was then applied for the analysis of target PFAAs in environmental water samples,
      and recoveries of 80.1-117% and 80.3-122% were obtained for target PFAAs in
      spiked Yangtze River and East Lake water samples respectively.

PMID- 29650481
TI  - Quantitative and comparative liquid chromatography-electrospray ionization-mass
      spectrometry analyses of hydrogen sulfide and thiol metabolites derivaitized with
      2-iodoacetanilide isotopologues.
AB  - Hydrogen sulfide (H2S), previously known as a toxic gas, is now recognized as a
      gasotransmitter along with nitric oxide and carbon monoxide. However, only few
      methods are available for quantitative determination of H2S in biological
      samples. 2-Iodoacetanilide (2-IAN), a thiol-reacting agent, has been used to tag
      the reduced cysteine residues of proteins for quantitative proteomics and for
      detection of cysteine oxidation modification. In this article, we proposed a new
      method for quantitative analyses of H2S and thiol metabolites using the procedure
      of pre-column 2-IAN derivatization coupled with liquid chromatography
      electrospray ionization-mass spectrometry (LC-ESI-MS). 13C6-Labeled and label
      free 2-IAN efficiently react with H2S and thiol compounds at pH 9.5 and 65 
      degrees C. The derivatives exhibit excellent stability at alkaline conditions,
      high resolution on reverse phase liquid chromatography and great sensitivity for
      ESI-MS detection. The measurement of H2S, l-cysteine, glutathione, and DL
      homocysteine derivatives was validated using 13C6-labeled standard in LC-ESI-MS
      analyses and exhibited 10 nM-1 MUM linear ranges for DL-homocysteine and
      glutathione and 1 nM-1 MUM linear ranges for l-cysteine and H2S. In addition, the
      sequence of derivatization and extraction of metabolites is important in the
      quantification of thiol metabolites suggesting the presence of matrix effects.
      Most importantly, labeling with 2-IAN and 13C6-2-IAN isotopologues could achieve
      quantitative and matched sample comparative analyses with minimal bias using our
      extraction and labeling procedures before LC-MS analysis.

PMID- 29650482
TI  - Optimization of a multiple headspace sorptive extraction method coupled to gas
      chromatography-mass spectrometry for the determination of volatile compounds in
      macroalgae.
AB  - A novel extraction technique is proposed in which the Multiple Headspace
      Extraction (MHE) approach is used in conjunction with Headspace Sorptive
      Extraction (HSSE) and Gas Chromatography-Mass Spectrometry (GC-MS) detection. The
      extraction method was developed to determine volatile compounds in macroalgae.
      Optimization of the extraction parameters was carried out using design of
      experiments to identify factors that affect the extraction: extraction time,
      temperature, twister length and amount of sample. The results of the optimization
      led to an extraction of 2 g of sample using a 20 mm Twister(r) at 66  degrees C
      for 180 min. The progression constants (beta) were calculated for 43 volatile
      compounds, 29 of which could be quantified using the method. Linearity was
      attained with a determination coefficient higher than 0.99 for all studied
      compounds. Inter-day and inter-twister precisions ranged from 0.22% to 19.01% and
      from 0.69% to 14.76% respectively, and values below 10% were obtained for the
      majority of compounds. LOD and LOQ values ranged from the values obtained for
      diethyl succinate (0.012 MUg/L and 0.088 MUg/L, respectively) and those obtained
      for dimethyl sulfide (5.544 MUg/L and 40.286 MUg/L, respectively). However, for
      the majority of compounds values obtained were below 1 MUg/L (LOD) and 5 MUg/L
      (LOQ). Compounds such as ethyl acetate, hexanal, heptadecane, 2-hexenal, 6-methyl
      5-hepten-2-one, dimethyl sulfide, benzyl alcohol, beta ionone, or beta
      cyclocitral, among others were correctly determined in three species of
      macroalgae: Ulva sp., Gracillaria sp. and Enteromorpha sp.

PMID- 29650483
TI  - Solid, Cystic, and Tubular: Novice Ultrasound Skills Training Using a Versatile,
      Affordable Practice Model.
AB  - OBJECTIVE: In spite of the recognized benefits of ultrasound, many physicians
      have little experience with using ultrasound to perform procedures. Many medical
      schools and residency programs lack a formal ultrasound training curriculum. We
      describe an affordable ultrasound training curriculum and versatile, inexpensive
      practice model. DESIGN: Participants underwent a didactic session to teach the
      theory required to perform ultrasound-guided procedures. Motor skills were taught
      using a practice model incorporating analogs of common anatomic and pathologic
      structures into an opacified gelatin substrate. SETTING: The Marcia and Eugene
      Applebaum Simulation Learning Institute, Beaumont Hospital, Royal Oak, MI; a
      private nonprofit tertiary care hospital associated with the OUWB School of
      Medicine, Rochester, MI. PARTICIPANTS: The model was tested in a cohort of 50
      medical students and general surgery residents. RESULTS: The gelatin model can be
      constructed for $1.03 per learner. The solid, cystic, and vascular structural
      analogs were readily identifiable on ultrasound and easily differentiated based
      on their echotextures. Eighty-four percent of participants successfully aspirated
      the cystic structure, 88% successfully biopsied a portion of the solid structure,
      and 76% successfully cannulated the tubular structure. Overall, 82% of
      participants achieved a passing score for the exercise based on a validated
      Objective Structured Assessment of Technical Skill instrument. There were no
      significant differences between the medical students and residents. CONCLUSION:
      This model can be used to teach basic ultrasound skills such as aspiration,
      biopsy, and vessel cannulation, providing a foundation for the use of ultrasound
      in a broad range of clinical procedures, as well as providing practice
      opportunities for medical students and residents to gain increased ultrasound
      competency and confidence.

PMID- 29650484
TI  - Identification of New Tools to Predict Surgical Performance of Novices using a
      Plastic Surgery Simulator.
AB  - OBJECTIVE: To identify new tools capable of predicting surgical performance of
      novices on an augmentation mammoplasty simulator. The pace of technical skills
      acquisition varies between residents and may necessitate more time than that
      allotted by residency training before reaching competence. Identifying applicants
      with superior innate technical abilities might shorten learning curves and the
      time to reach competence. The objective of this study is to identify new tools
      that could predict surgical performance of novices on a mammoplasty simulator.
      METHOD: We recruited 14 medical students and recorded their performance in 2
      skill-games: Mikado and Perplexus Epic, and in 2 video games: Star War Racer
      (Sony Playstation 3) and Super Monkey Ball 2 (Nintendo Wii). Then, each
      participant performed an augmentation mammoplasty procedure on a Mammoplasty Part
      task Trainer, which allows the simulation of the essential steps of the
      procedure. RESULTS: The average age of participants was 25.4 years. Correlation
      studies showed significant association between Perplexus Epic, Star Wars Racer,
      Super Monkey Ball scores and the modified OSATS score with rs = 0.8491 (p <
      0.001), rs = -0.6941 (p = 0.005), and rs = 0.7309 (p < 0.003), but not with the
      Mikado score rs = -0.0255 (p = 0.9). Linear regressions were strongest for
      Perplexus Epic and Super Monkey Ball scores with coefficients of determination of
      0.59 and 0.55, respectively. A combined score (Perplexus/Super-Monkey-Ball) was
      computed and showed a significant correlation with the modified OSATS score
      having an rs = 0.8107 (p < 0.001) and R2 = 0.75, respectively. CONCLUSIONS: This
      study identified a combination of skill games that correlated to better
      performance of novices on a surgical simulator. With refinement, such tools could
      serve to help screen plastic surgery applicants and identify those with higher
      surgical performance predictors.

PMID- 29650485
TI  - Providing Transthoracic Echocardiography Training for Intensive Care Unit
      Trainees: An Educational Improvement Initiative.
AB  - OBJECTIVE: Transthoracic echocardiography (TTE) is important in the management of
      critically ill patients, yet it has not been incorporated into many residency
      programs' curricula. Our objective is to determine if trainees undergoing a 60
      minute training session on TTE have improved knowledge, ultrasound skills, and
      increases the utilization of TTE during their rotation in the intensive care unit
      (ICU). We will also compare the results of participants with prior TTE exposure
      to TTE-naive trainees. Our hypothesis is that after the training, participants'
      will have improved knowledge and ultrasound skills compared to before training.
      Our secondary hypotheses are that TTE-naive trainees will have greater
      improvements in knowledge scores compared to those who have had prior TTE
      experience and trainees will increase their use of TTE in the ICU. DESIGN: Single
      center, prospective trial. SETTING: Brigham and Women's Hospital (academic
      hospital). PARTICIPANTS: Residents and fellows rotating through the ICU, at any
      level of postgraduate training. RESULTS: Forty-two trainees participated in the
      study. Statistically significant improvement after training was observed for all
      multiple choice questions (MCQ) and practical assessments (p < 0.001). When
      assessing the differences in score improvement between TTE-experienced versus TTE
      naive users, mean score improvements were notably higher for TTE-naive
      participants (MCQ: 28.2 +/- 11.6; echo clinical: 48.6 +/- 23.4) compared to TTE
      experienced users (MCQ: 18.6 +/- 13.5, p = 0.01; echo clinical: 38.3 +/- 30.2, p
      = 0.04). CONCLUSIONS: A short didactic presentation on TTE use may be useful in
      teaching ICU trainees basic TTE skills and encouraging the use of bedside TTE in
      the ICU.

PMID- 29650486
TI  - A Vascular Anastomosis Simulation Can Provide a Safe and Effective Environment
      for Resident Skills Development.
AB  - OBJECTIVE: Vascular anastomoses are complex surgical procedures, performed in
      time-sensitive circumstances, making intraoperative teaching more challenging. We
      sought to evaluate whether a vascular anastomosis simulation was effective in
      developing resident skills. DESIGN, SETTING, PARTICIPANTS: General surgery
      residents participated in a vascular anastomosis simulation for 1 to 2hours
      during their transplant rotation. An attending transplant surgeon at the
      University of Colorado guided the resident through end-to-end and end-to-side
      anastomoses using bovine carotid artery (Artegraft). The residents completed a
      presimulation and postsimulation survey which quantitated their confidence. They
      also completed the MiSSES scale, which assessed the validity of the simulation.
      RESULTS: Twenty residents participated in the simulation and completed the
      surveys. The residents reported increased understanding in how to set up an end
      to-end anastomosis and an end-to-side anastomosis (p = 0.001 and p = 0.009,
      respectively). They reported increased ability to suture, forehand and backhand
      with a Castro-Viejo needle driver (both p < 0.001). The residents reported
      increased ability to manipulate the needle (p = 0.006), and increased ability to
      manipulate tissue without causing trauma (p = 0.021). They reported increased
      confidence in tying a surgical knot with 6-0 Prolene and in operating while
      wearing loupes (p = 0.002, and p < 0.001, respectively). Overall, the residents
      reported increased confidence when asked to perform part of a vascular
      anastomosis in the operating room (p < 0.001). Seventeen residents completed the
      MiSSES scale with median scores of "somewhat agree" to "strongly agree" on all
      domains of the scale. CONCLUSIONS: The use of a simple, inexpensive vascular
      anastomosis simulation is an effective and safe environment to improve residents'
      surgical skills and the residents felt that the simulation was valid.

PMID- 29650487
TI  - Speaking up about hand hygiene failures: A vignette survey study among healthcare
      professionals.
AB  - BACKGROUND: Speaking up by healthcare professionals (HCPs) is an important
      resource to reduce risks to patient safety. Due to complex tradeoffs, HCPs are
      often reluctant to voice their concerns. A survey investigated HCPs' likelihood
      to speak up. METHODS: A cross-sectional survey study among HCPs in 5 Swiss
      hospitals addressed speaking-up behaviors, safety climate, and likelihood to
      speak up about poor hand hygiene practice described in a vignette. Likelihood to
      speak up was analyzed using a multilevel regression model. RESULTS: Of surveyed
      HCPs (n = 1217), 56% reported that they would speak up to a colleague with poor
      hand hygiene practice. Nurses as compared to doctors rated the situation as more
      realistic (5.25 vs 4.32, P < .001), felt more discomfort with speaking up (4.00
      vs 3.34, P < .001), and reported a slightly lower likelihood of speaking up (4.41
      vs 4.77, P < .001). Clinical function (hierarchy) was strongly associated with
      speaking-up behavior (P < .001). Higher risk of harm to the patient (P < .001)
      and higher frequencies of past speaking-up behaviors (P = .006) were positively
      associated with the likelihood to speak up. Higher frequencies of past
      withholding voice (P = .013) and higher levels of resignation (P = .008) were
      both associated with a lower likelihood to speak up. CONCLUSIONS: Infection
      control interventions should empower HCPs to speak up about non-adherence with
      prevention practices by addressing authority gradients and risk perceptions and
      by focusing on resignation.

PMID- 29650488
TI  - Comments on Multidrug-resistant acinetobacter: Risk factors and outcomes in
      veterans with spinal cord injuries and disorders.

PMID- 29650489
TI  - Guiding hand hygiene interventions among future healthcare workers: implications
      of knowledge, attitudes, and social influences.
AB  - BACKGROUND: Medical students in their clinical years play an important role in
      healthcare delivery, yet poor levels of hand hygiene (HH) compliance in this
      population raise the risk for propagating nosocomial infections. To date, there
      has been a lack of dedicated interventions showing sustainable improvements in HH
      in this population. METHODS: A multicenter, cross-sectional study was conducted
      among 450 medical students in their clinical years (third to fifth years). A self
      administered, pre-validated questionnaire based on the World Health
      Organization's "Knowledge" and "Perception" questionnaires was used to explore HH
      knowledge, attitudes, practices, and desired interventions. RESULTS: Self
      reported HH compliance was found to be low (56.8%), and moderate HH knowledge
      (61.8%) was observed among all study respondents. Public university students
      expressed greater knowledge than students in private and semi-private
      universities. Superior HH practices were associated with better individual HH
      attitudes, positive perceived HH attitudes in other healthcare workers (HCWs),
      and higher HH knowledge scores. The highest-rated interventions for improving HH
      compliance included role-modeling by HCWs, display of "clear HH instructions,"
      and "ensuring availability of hand sanitizers." CONCLUSION: Our results call for
      a multifaceted approach to improve HH compliance among medical students, by
      ensuring adequate HH supplies/hand sanitizers, providing HH training in
      curricula, and effecting a cultural change mediated by professional modeling and
      open communication.

PMID- 29650490
TI  - A Klinefelter patient with an additional mitochondrial mutation: Implications for
      genotype-driven treatment and mitochondrial mutational load in different tissues
      and family members.

PMID- 29650492
TI  - Robotically-driven orthoses exert proximal-to-distal differential recovery on the
      lower limbs in children with hemiplegia, early after acquired brain injury.
AB  - Robotically-driven orthoses (RDO) are promising for treating gait impairment in
      children with hemiplegia after acquired brain injury (ABI). Despite this,
      existing literature on the employment of RDO in ABI is scanty, and cohorts' age
      spans throughout the adult age, with no specific focus on the developmental age.
      We aim to compare a treatment solely based on conventional physiotherapy (CP)
      with a program combining RDO training with CP, and to examine the effect of time
      following ABI on recovery. A prospective two-cohorts study was conducted in a
      rehabilitation hospital. Post-acute and chronic children with hemiplegia due to
      ABI underwent either: (i) 20 sessions of RDO plus 20 sessions of CP (n = 29), or
      (ii) 40 of CP (n = 12). Gross Motor Function Measures (GMFM), Functional
      Assessment Questionnaire (FAQ), 6 Minutes Walk Test and gait analysis (GA)
      parameters were recorded before and after training. Over all the patients in RDO
      + CP group, all GMFM domains and FAQ improved after RDO training (p < 0.05). The
      unaffected limb showed significantly decreased stance, increased step length and
      reduced anteroposterior center of pressure oscillation; the affected side
      increased the stride length. ROM hip and knee flex-extension increased
      bilaterally (p < 0.05 for all). RDO training during the acute/subacute post
      injury phase increased motor functional abilities, cadence and velocity of gait
      (p < 0.05). We conclude that RDO imposes a proximal-to-distal differential effect
      on the lower limbs, with the hip joint being the most stimulated. RDO training
      fostered recovery, increasing the quality of gait on the unaffected side.
      Planning RDO early in the rehabilitation course of pediatric ABI is advantageous.
      RDO + CP may extend rehabilitation efficacy to the proximal segment of leg and to
      gait velocity.

PMID- 29650493
TI  - Exposure to Coxiella burnetii and risk of non-Hodgkin lymphoma: a retrospective
      population-based analysis in the Netherlands.
AB  - BACKGROUND: An association between Coxiella burnetii and non-Hodgkin lymphoma has
      been suggested. After a large Q fever epidemic in the Netherlands (2007-10), we
      postulated that the incidence of non-Hodgkin lymphoma would be increased during
      and after the epidemic in areas with a high endemicity of Q fever compared with
      those with low endemicity. METHODS: We did a retrospective population-based
      analysis and calculated relative risks (RRs) of non-Hodgkin lymphoma during 1
      year periods before, during, and after the Q fever epidemic, for areas with
      intermediate and high endemicity of Q fever compared with low endemic areas. We
      also calculated the RR of non-Hodgkin lymphoma in people with chronic Q fever
      compared with the general population. FINDINGS: Between Jan 1, 2002, and Dec 31,
      2013, 48 760 cases of non-Hodgkin lymphoma were diagnosed. The incidence of non
      Hodgkin lymphoma ranged from 21.4 per 100 000 per year in 2002 to 26.7 per 100
      000 per year in 2010. A significant association with non-Hodgkin lymphoma was
      noted in 2009 for areas with a high endemicity of Q fever compared with low
      endemic areas (RR 1.16, 95% CI 1.02-1.33; p=0.029); no further associations were
      noted in any other year or for areas with intermediate Q fever endemicity. Among
      439 individuals with chronic Q fever, five developed non-Hodgkin lymphoma,
      yielding a crude absolute risk of 301.0 cases per 100 000 per year (RR 4.99, 95%
      CI 2.07-11.98; p=0.0003) compared with the general population in the Netherlands.
      INTERPRETATION: These findings do not support the hypothesis that Q fever has a
      relevant causal role in the development of non-Hodgkin lymphoma. Several
      limitations, inherent to the design of this study, might lead to both
      underestimation and overestimation of the studied association. FUNDING:
      Foundation Q-support and Institut Merieux.

PMID- 29650491
TI  - Fecal Microbiota Composition Drives Immune Activation in HIV-infected
      Individuals.
AB  - The inflammatory properties of the enteric microbiota of Human Immunodeficiency
      Virus (HIV)-infected individuals are of considerable interest because of strong
      evidence that bacterial translocation contributes to chronic immune activation
      and disease progression. Altered enteric microbiota composition occurs with HIV
      infection but whether altered microbiota composition or increased intestinal
      permeability alone drives peripheral immune activation is controversial. To
      comprehensively assess the inflammatory properties of HIV-associated enteric
      microbiota and relate these to systemic immune activation, we developed methods
      to purify whole fecal bacterial communities (FBCs) from stool for use in in vitro
      immune stimulation assays with human cells. We show that the enteric microbiota
      of untreated HIV-infected subjects induce significantly higher levels of
      activated monocytes and T cells compared to seronegative subjects. FBCs from anti
      retroviral therapy (ART)-treated HIV-infected individuals induced intermediate T
      cell activation, indicating an only partial correction of adaptive immune cell
      activation capacity of the microbiome with ART. In vitro activation levels
      correlated with activation levels and viral load in blood and were particularly
      high in individuals harboring specific gram-positive opportunistic pathogens.
      Blockade experiments implicated Tumor Necrosis Factor (TNF)-alpha and Toll-Like
      Receptor-2 (TLR2), which recognizes peptidoglycan, as strong mediators of T cell
      activation; This may contradict a previous focus on lipopolysaccharide as a
      primary mediator of chronic immune activation. These data support that increased
      inflammatory properties of the enteric microbiota and not increased permeability
      alone drives chronic inflammation in HIV.

PMID- 29650494
TI  - Does Q fever contribute to pathogenesis of non-Hodgkin lymphoma?

PMID- 29650495
TI  - A Fine doctor.
AB  - I met Jonathan Fine for the first time in 2011. He was to travel back to Boston
      through Mumbai after a stint in Chattisgarh, where he had volunteered with Jan
      Swasthya Sahayog, the well-known rural hospital near Bilaspur. A friend suggested
      that since he was a doctor who had done pioneering work by setting up the
      renowned organisation Physicians for Human Rights, we should arrange a talk by
      him for medical students. A lecture was thus organised at my alma mater, the GS
      Medical College and KEM Hospital, where Jonathan spoke on "Why should doctors
      engage with human rights?" In his characteristic blunt style, rather than talk
      about his past, he exhorted the audience to visit Chattisgarh and see the severe
      inequities he had witnessed.

PMID- 29650496
TI  - Reporting ethical processes in the Nursing Journal of India.
AB  - Nursing research is a developing field to which individuals within the profession
      can contribute substantially based on their skills and practical experience of
      nursing care. Both reporting of informed consent and ethical approval are key
      aspects of published papers which indicate the researchers' knowledge of and
      sensitivity to ethical aspects of research.

PMID- 29650497
TI  - Quality of medical education: Is our health in safe hands?
AB  - The medical profession, once considered a "noble profession" has been under the
      scanner for deterioration in services. This decline is generally attributed to
      commercialisation of services, waning human values, and a lack of empathy and
      communication skills. At a time when discussions are focused on devising
      approaches to test medical students for attributes such as empathy, communication
      skills and concern for the less privileged, developing nations like India are
      suffering from the "problem of too many". On the one hand, a skewed doctor
      patient ratio in India (less than 1 doctor per 1000 people that is lower than
      that prescribed by the World Health Organisation) has left medical practitioners
      so overburdened, they have little time to empathise with their patients. Students
      inadvertently follow their teachers and the vicious cycle continues. On the other
      hand, there has been a mushrooming of commercially-run medical institutions to
      overcome this shortage of doctors. Medical education has become unaffordable to
      many and, very obviously, merit has taken a back seat.

PMID- 29650498
TI  - Five years post Nirbhaya: Critical insights into the status of response to sexual
      assault.
AB  - It is five years since the fatal gang rape of Jyothi Singh (Nirbhaya), a
      physiotherapy student, on December 16, 2012, in New Delhi, the capital of India.
      The legal and policy reforms triggered by the Nirbhaya case will remain a
      watershed moment in the history of efforts towards seeking justice for survivors
      of gender-based violence in India. The Criminal Law (Amendment) Act, 2013 and the
      "Guidelines and protocols: Medico-legal care for survivors/victims of sexual
      violence" issued by the Ministry of Health and Family Welfare in March 2014 are
      two landmark reforms. March 2018 marks four years since the issuance of these
      Guidelines and five years since the Criminal Law (Amendment) Act, 2013. Any
      reasonable tribute to Nirbhaya would constitute fair implementation of legal
      reforms, efforts to strengthen multi-sectoral response and sincere attempts to
      reduce crimes against women, gender and sexual minorities, and children. This
      paper reviews the issue, through a close study of recent cases of rape, police
      responses, court judgements, studies, news reporting and field-based
      observations. It brings forth the gaps in implementation that persist, and
      constitute a major obstacle in making these progressive policies and reforms
      effective. Given the fact that the reforms are intersectoral in nature,
      implementation has been particularly challenging. Lack of efficient
      implementation of such policies and reforms amounts to denying survivors their
      right to justice.

PMID- 29650499
TI  - Evaluation of research in India - are we doing it right?
AB  - The evaluation of performance in scientific research at any level - whether at
      the individual, institutional, research council or country level - is not easy.
      Traditionally, research evaluation at the individual and institutional levels has
      depended largely on peer opinion, but with the rapid growth of science over the
      last century and the availability of databases and scientometric techniques,
      quantitative indicators have gained importance. Both peer review and metrics are
      subject to flaws, more so in India because of the way they are used. Government
      agencies, funding bodies and academic and research institutions in India suffer
      from the impact factor and h-index syndrome. The uninformed use of indicators
      such as average and cumulative impact factors and the arbitrary criteria
      stipulated by agencies such as the University Grants Commission, Indian Council
      of Medical Research and the Medical Council of India for selection and promotion
      of faculty have made it difficult to distinguish good science from the bad and
      the indifferent. The exaggerated importance given by these agencies to the number
      of publications, irrespective of what they report, has led to an ethical crisis
      in scholarly communication and the reward system in science. These agencies seem
      to be unconcerned about the proliferation of predatory journals and conferences.
      After giving examples of the bizarre use of indicators and arbitrary recruitment
      and evaluation practices in India, we summarise the merits of peer review and
      quantitative indicators and the evaluation practices followed elsewhere.

PMID- 29650500
TI  - Zika reveals India's risk communication challenges and needs.
AB  - India's approach to disseminating information about the first three cases of the
      Zika virus was criticised nationally and internationally after the issue came to
      light in May 2017 through a World Health Organization news release. We analyse
      the incident from a risk communication perspective. This commentary recaps the
      events and synthesises key arguments put forth by the news media and public
      health stakeholders. We use Peter Sandman's risk = hazard + outrage framework -
      also adopted by India's risk communication planners - to analyse India's risk
      communication response and contextualise it against the mandate of the National
      Risk Communication Plan and Integrated Disease Surveillance Programme. We
      conclude with recommendations for India's risk communication policymakers,
      including the need to develop capacity for risk communication research and
      scholarship in the country.

PMID- 29650501
TI  - Social responsibility and global health: lessons from the Rio Olympics Zika
      controversy.
AB  - The outbreak of Zika virus infection in the Americas and its possible association
      with microcephaly raised several concerns among global health authorities
      regarding the organisation of the Olympic and Paralympic Games scheduled for
      August and September 2016, in the city of Rio de Janeiro, Brazil. It generated an
      international controversy over the continuation of the Games with debates on the
      ethical principle of social responsibility. Based on the principles of social
      responsibility and health in the Universal Declaration of Bioethics and Human
      Rights, the present comment ponders on the application of such principles in the
      context of mega-events and global health.

PMID- 29650502
TI  - Prevalence of Multiple Chronic Conditions Among Older Adults in Florida and the
      United States: Comparative Analysis of the OneFlorida Data Trust and National
      Inpatient Sample.
AB  - BACKGROUND: Older patients with multiple chronic conditions are often faced with
      increased health care needs and subsequent higher medical costs, posing
      significant financial burden to patients, their caregivers, and the health care
      system. The increasing adoption of electronic health record systems and the
      proliferation of clinical data offer new opportunities for prevalence studies and
      for population health assessment. The last few years have witnessed an increasing
      number of clinical research networks focused on building large collections of
      clinical data from electronic health records and claims to make it easier and
      less costly to conduct clinical research. OBJECTIVE: The aim of this study was to
      compare the prevalence of common chronic conditions and multiple chronic
      conditions in older adults between Florida and the United States using data from
      the OneFlorida Clinical Research Consortium and the Healthcare Cost and
      Utilization Project (HCUP) National Inpatient Sample (NIS). METHODS: We first
      analyzed the basic demographic characteristics of the older adults in 3 datasets
      the 2013 OneFlorida data, the 2013 HCUP NIS data, and the combined 2012 to 2016
      OneFlorida data. Then we analyzed the prevalence of each of the 25 chronic
      conditions in each of the 3 datasets. We stratified the analysis of older adults
      with hypertension, the most prevalent condition. Additionally, we examined trends
      (ie, overall trends and then by age, race, and gender) in the prevalence of
      discharge records representing multiple chronic conditions over time for the
      OneFlorida (2012-2016) and HCUP NIS cohorts (2003-2013). RESULTS: The rankings of
      the top 10 prevalent conditions are the same across the OneFlorida and HCUP NIS
      datasets. The most prevalent multiple chronic conditions of 2 conditions among
      the 3 datasets were-hyperlipidemia and hypertension; hypertension and ischemic
      heart disease; diabetes and hypertension; chronic kidney disease and
      hypertension; anemia and hypertension; and hyperlipidemia and ischemic heart
      disease. We observed increasing trends in multiple chronic conditions in both
      data sources. CONCLUSIONS: The results showed that chronic conditions and
      multiple chronic conditions are prevalent in older adults across Florida and the
      United States. Even though slight differences were observed, the similar
      estimates of prevalence of chronic conditions and multiple chronic conditions
      across OneFlorida and HCUP NIS suggested that clinical research data networks
      such as OneFlorida, built from heterogeneous data sources, can provide rich data
      resources for conducting large-scale secondary data analyses.

PMID- 29650503
TI  - Instructional Video and Medical Student Surgical Knot-Tying Proficiency:
      Randomized Controlled Trial.
AB  - BACKGROUND: Many senior medical students lack simple surgical and procedural
      skills such as knot tying. OBJECTIVE: The aim of this study was to determine
      whether viewing a Web-based expert knot-tying training video, in addition to the
      standard third-year medical student curriculum, will result in more proficient
      surgical knot tying. METHODS: At the start of their obstetrics and gynecology
      clerkship, 45 students were videotaped tying surgical knots for 2 minutes using a
      board model. Two blinded female pelvic medicine and reconstructive surgery
      physicians evaluated proficiency with a standard checklist (score range 0-16) and
      anchored scoring scale (range 0-20); higher numbers represent better skill.
      Students were then randomized to either (1) expert video (n=26) or (2) nonvideo
      (n=24) groups. The video group was provided unlimited access to an expert knot
      tying instructional video. At the completion of the clerkship, students were
      again videotaped and evaluated. RESULTS: At initial evaluation, preclerkship
      cumulative scores (range 0-36) on the standard checklist and anchored scale were
      not significantly different between the nonvideo and video groups (mean 20.3, SD
      7.1 vs mean 20.2, SD 9.2, P=.90, respectively). Postclerkship scores improved in
      both the nonvideo and video groups (mean 28.4, SD 5.4, P<.001 and mean 28.7, SD
      6.5, P=.004, respectively). Increased knot board practice was significantly
      correlated with higher postclerkship scores on the knot-tying task, but only in
      the video group (r=.47, P<.05). CONCLUSIONS: The addition of a Web-based expert
      instructional video to a standard curriculum, coupled with knot board practice,
      appears to have a positive impact on medical student knot-tying proficiency.

PMID- 29650504
TI  - Interactive Two-Way mHealth Interventions for Improving Medication Adherence: An
      Evaluation Using The Behaviour Change Wheel Framework.
AB  - BACKGROUND: Medication adherence is an important but highly complex set of
      behaviors, which for life-threatening and infectious diseases such as HIV carry
      critical consequences for individual and public health. There is growing evidence
      that mobile phone text messaging interventions (mHealth) connecting providers
      with patients positively impact medication adherence, particularly two-way
      engagement platforms that require bidirectional communication versus one-way in
      which responses are not mandatory. However, mechanisms of action have not been
      well defined. The Behavior Change Wheel is a comprehensive framework for behavior
      change that includes an all-encompassing model of behavior known as Capability
      Opportunity Motivation-Behavior and is complemented by a taxonomy of behavior
      change techniques. Evaluating mHealth interventions for medication adherence
      using these tools could provide useful insights that may contribute to optimizing
      their integration into the healthcare system and successful scaling-up.
      OBJECTIVE: This study aimed to help address the current knowledge gap regarding
      how two-way mHealth interventions for medication adherence may work by applying
      the Behavior Change Wheel to characterize WelTel: an interactive digital health
      outreach platform with robust evidence for improving adherence to antiretroviral
      therapy. METHODS: To characterize how WelTel may promote medication adherence, we
      applied the Behavior Change Wheel to systematically (1) generate a behavioral
      diagnosis through mapping known antiretroviral therapy adherence barriers onto
      the Capability Opportunity Motivation-Behavior model of behavior, (2) specify the
      behavior change techniques that WelTel delivers, (3) link identified behavior
      change techniques to corresponding intervention functions of the Behavior Change
      Wheel, and (4) connect these behavior change techniques and intervention
      functions to respective Capability Opportunity Motivation-Behavior influences on
      behavior to determine potential mechanisms of action. RESULTS: Our evaluation of
      WelTel using the Behavior Change Wheel suggests that most of its impact is
      delivered primarily through its personalized communication component, in which 8
      different behavior change techniques were identified and linked with 5
      intervention functions (environmental restructuring, enablement, education,
      persuasion, and training). Its mechanisms of action in promoting antiretroviral
      therapy adherence may involve addressing all Capability Opportunity Motivation
      Behavior influences on behavior (physical and psychological capability, physical
      and social opportunity, reflective and automatic motivation). CONCLUSIONS:
      Systematically unpacking the potential active ingredients of effective
      interventions facilitates the creation and implementation of more parsimonious,
      tailored, and targeted approaches. Evaluating WelTel using the Behavior Change
      Wheel has provided valuable insights into how and why such interactive two-way
      mHealth interventions may produce greater impact than one-way in addressing both
      nonintentional and intentional forms of nonadherence. The application of the
      Behavior Change Wheel for evidence synthesis across mHealth interventions
      targeting various conditions would contribute to strengthening the knowledge base
      regarding how they may work to impact medication adherence behavior.

PMID- 29650505
TI  - Universal Versus Conditional Third Day Follow-Up Visit for Children With
      Nonsevere Unclassified Fever at the Community Level in Ethiopia: Protocol for a
      Cluster Randomized Noninferiority Trial.
AB  - BACKGROUND: Under the World Health Organization's integrated community case
      management strategy, febrile children seen by community health workers (on day 1)
      without a diagnosable illness and without danger signs are advised to return on
      day 3, regardless of symptom resolution. This advice might be unnecessary and
      place additional time and cost burdens on caregivers and community health
      workers. However, the safety of not following up with respect to children with
      unclassified fever is unknown. OBJECTIVE: The objective of this study is to
      establish the safety of conditional follow-up of nonsevere unclassified fever,
      that is, nonsevere illness with fever, no malaria, pneumonia, diarrhea, or danger
      signs, compared with universal follow-up on day 3, through a 2-arm cluster
      randomized controlled noninferiority trial. METHODS: The study is being conducted
      in 3 districts in southwest Ethiopia. A total of 25 health facilities are
      randomized to one of the 2 intervention arms; all 144 health posts and 284
      community health workers are included. All enrolled children are followed-up
      after 1 week (on day 8) for re-assessment. If still sick on day 8, additional
      follow-up takes place after 2 weeks (day 15) and 1 month (day 29). To demonstrate
      that there is no significant increase in the percentage of children deteriorating
      clinically, the sample size needed for a noninferiority margin of 4%, a power of
      80%, an alpha of 5%, and a design effect of 3 is 4284 children with unclassified
      fever. Main outcome is treatment failure on day 8, defined as death,
      hospitalization, one or more danger signs, or persistent fever. RESULTS: The
      project was funded in 2015 and enrollment was completed 2016. Data analysis is
      currently under way, and the first results are expected to be submitted for
      publication in 2018. CONCLUSIONS: This study addresses the question as to whether
      there is any benefit in recommending universal follow-up among children seen for
      nonsevere unclassified fever, or whether parents can be counseled to return in
      the event of persistent fever, using a cluster randomized controlled trial design
      embedded in a national program. Outcomes will be relevant for policy makers and
      are important for the evaluation of current and future World Health Organization
      guidelines for the management of children with fever. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT02926625; https://clinicaltrials.gov/ct2/show/NCT02926625
      (Archived by WebCite at http://www.webcitation.org/6xrQWn50t).

PMID- 29650506
TI  - Evaluating the Validity of Current Mainstream Wearable Devices in Fitness
      Tracking Under Various Physical Activities: Comparative Study.
AB  - BACKGROUND: Wearable devices have attracted much attention from the market in
      recent years for their fitness monitoring and other health-related metrics;
      however, the accuracy of fitness tracking results still plays a major role in
      health promotion. OBJECTIVE: The aim of this study was to evaluate the accuracy
      of a host of latest wearable devices in measuring fitness-related indicators
      under various seminatural activities. METHODS: A total of 44 healthy subjects
      were recruited, and each subject was asked to simultaneously wear 6 devices
      (Apple Watch 2, Samsung Gear S3, Jawbone Up3, Fitbit Surge, Huawei Talk Band B3,
      and Xiaomi Mi Band 2) and 2 smartphone apps (Dongdong and Ledongli) to measure
      five major health indicators (heart rate, number of steps, distance, energy
      consumption, and sleep duration) under various activity states (resting, walking,
      running, cycling, and sleeping), which were then compared with the gold standard
      (manual measurements of the heart rate, number of steps, distance, and sleep, and
      energy consumption through oxygen consumption) and calculated to determine their
      respective mean absolute percentage errors (MAPEs). RESULTS: Wearable devices had
      a rather high measurement accuracy with respect to heart rate, number of steps,
      distance, and sleep duration, with a MAPE of approximately 0.10, whereas poor
      measurement accuracy was observed for energy consumption (calories), indicated by
      a MAPE of up to 0.44. The measurements varied for the same indicator measured by
      different fitness trackers. The variation in measurement of the number of steps
      was the highest (Apple Watch 2: 0.42; Dongdong: 0.01), whereas it was the lowest
      for heart rate (Samsung Gear S3: 0.34; Xiaomi Mi Band 2: 0.12). Measurements
      differed insignificantly for the same indicator measured under different states
      of activity; the MAPE of distance and energy measurements were in the range of
      0.08 to 0.17 and 0.41 to 0.48, respectively. Overall, the Samsung Gear S3
      performed the best for the measurement of heart rate under the resting state
      (MAPE of 0.04), whereas Dongdong performed the best for the measurement of the
      number of steps under the walking state (MAPE of 0.01). Fitbit Surge performed
      the best for distance measurement under the cycling state (MAPE of 0.04), and
      Huawei Talk Band B3 performed the best for energy consumption measurement under
      the walking state (MAPE of 0.17). CONCLUSIONS: At present, mainstream devices are
      able to reliably measure heart rate, number of steps, distance, and sleep
      duration, which can be used as effective health evaluation indicators, but the
      measurement accuracy of energy consumption is still inadequate. Fitness trackers
      of different brands vary with regard to measurement of indicators and are all
      affected by the activity state, which indicates that manufacturers of fitness
      trackers need to improve their algorithms for different activity states.

PMID- 29650507
TI  - Recruitment of Participants and Delivery of Online Mental Health Resources for
      Depressed Individuals Using Tumblr: Pilot Randomized Control Trial.
AB  - BACKGROUND: Adolescents and young adults frequently post depression symptom
      references on social media; previous studies show positive associations between
      depression posts and self-reported depression symptoms. Depression is common
      among young people and this population often experiences many barriers to mental
      health care. Thus, social media may be a new resource to identify, recruit, and
      intervene with young people at risk for depression. OBJECTIVE: The purpose of
      this pilot study was to test a social media intervention on Tumblr. We used
      social media to identify and recruit participants and to deliver the intervention
      of online depression resources. METHODS: This randomized pilot intervention
      identified Tumblr users age 15-23 who posted about depression using the search
      term "#depress". Eligible participants were recruited via Tumblr messages;
      consented participants completed depression surveys and were then randomized to
      an intervention of online mental health resources delivered via a Tumblr message,
      while control participants did not receive resources. Postintervention online
      surveys assessed resource access and usefulness and control groups were asked
      whether they would have liked to receive resources. Analyses included t tests.
      RESULTS: A total of 25 participants met eligibility criteria. The mean age of the
      participants was 17.5 (SD 1.9) and 65% were female with average score on the
      Patient Health Questionnaire-9 of 17.5 (SD 5.9). Among the 11 intervention
      participants, 36% (4/11) reported accessing intervention resources and 64% (7/11)
      felt the intervention was acceptable. Among the 14 control participants, only 29%
      (4/14) of reported that receiving resources online would be acceptable (P=.02).
      Participants suggested anonymity and ease of use as important characteristics in
      an online depression resource. CONCLUSIONS: The intervention was appropriately
      targeted to young people at risk for depression, and recruitment via Tumblr was
      feasible. Most participants in the intervention group felt the social media
      approach was acceptable, and about a third utilized the online resources.
      Participants who had not experienced the intervention were less likely to find it
      acceptable. Future studies should explore this approach in larger samples. Social
      media may be an appropriate platform for online depression interventions for
      young people.

PMID- 29650508
TI  - Why a change of diagnosis shouldn't matter . . . but it does.

PMID- 29650509
TI  - Cardiovascular disease risk factor clustering in children and adolescents: a
      prospective cohort study.
AB  - OBJECTIVE: The early identification of predictors related to cardiovascular
      disease risk factor clustering (CVD-RFC) can help prevent chronic disease. We
      aimed to identify the risk factors for CVD-RFC in adolescents. METHODS: A
      prospective longitudinal cohort study design was used to obtain data included in
      these analyses from school-aged children who participated in the Korean Child
      Adolescent Study 2008-2014. A total of 1309 children aged 6-15 years were
      enrolled. We compared the participants based on the presence or absence of CVD
      RFC and examined the cumulative incidence of CVD-RFC. RESULTS: Of the total 1309
      children, 410 (31.32%) had CVD-RFC in adolescence. A higher average household
      income >=3 million Korean Republic won (KRW)/month (3-5 million KRW/month: HR
      0.75 (95% CI 0.58 to 0.97); >=5 million KRW/month: HR 0.58 (95% CI 0.44 to 0.77))
      was associated with a lower CVD-RFC incidence, while the presence of parental CVD
      history (HR 1.28 (95% CI 1.04 to 1.57)), overweight or obesity (HR 3.83 (95% CI
      3.05 to 4.80)) and shorter sleep duration of 8-9 hour/day (HR 1.80 (95% CI 1.05
      to 3.07)) and <8 hour/day (HR 1.93 (95% CI 1.11 to 3.34)) had higher CVD-RFC
      incidences. CONCLUSIONS: Obesity in childhood, short sleep duration and parental
      factors such as low socioeconomic status and parental history of CVD are
      significant risk factors for the development of CVD-RFC in adolescents. Efforts
      to create awareness regarding sufficient sleep duration in children via
      intervention programmes targeting cardiometabolic health in children and special
      attention to lifestyle modifications and socioeconomic components of the family
      should be considered.

PMID- 29650510
TI  - Assessment and support of children and adolescents with gender dysphoria.

PMID- 29650511
TI  - Latest waiting time figures for emergency departments in England are worse on
      record.

PMID- 29650512
TI  - Updating NHS technologies: a WhatsApp-like system would improve communication.

PMID- 29650513
TI  - Lyme disease: summary of NICE guidance.

PMID- 29650516
TI  - Seven days in medicine: 4-10 April 2018.

PMID- 29650517
TI  - Should we try to manage non-financial interests?

PMID- 29650519
TI  - Whales, toxins, and a way of life.

PMID- 29650518
TI  - Secretory IgM Exacerbates Tumor Progression by Inducing Accumulations of MDSCs in
      Mice.
AB  - Chronic lymphocytic leukemia (CLL) cells can secrete immunoglobulin M. However,
      it is not clear whether secretory IgM (sIgM) plays a role in disease progression.
      We crossed the EMU-TCL1 mouse model of CLL, in which the expression of human TCL1
      oncogene was driven by the V(H) promoter-Ig(H)-EMU enhancer, with MD4 mice whose
      B cells produced B-cell receptor (membrane-bound IgM) and sIgM with specificity
      for hen egg lysozyme (HEL). CLL cells that developed in these MD4/EMU-TCL1 mice
      reactivated a parental Ig gene allele and secreted IgM, and did not recognize
      HEL. The MD4/EMU-TCL1 mice had reduced survival, increased myeloid-derived
      suppressor cells (MDSC), and decreased numbers of T cells. We tested whether sIgM
      could contribute to the accumulation of MDSCs by crossing MUS-/- mice, which
      could not produce sIgM, with EMU-TCL1 mice. The MUS-/-/EMU-TCL1 mice survived
      longer than EMU-TCL1 mice and developed decreased numbers of MDSCs which were
      less able to suppress proliferation of T cells. We targeted the synthesis of sIgM
      by deleting the function of XBP-1s and showed that targeting XBP-1s genetically
      or pharmacologically could lead to decreased sIgM, accompanied by decreased
      numbers and reduced functions of MDSCs in MD4/EMU-TCL1 mice. Additionally, MDSCs
      from MUS-/- mice grafted with Lewis lung carcinoma were inefficient suppressors
      of T cells, resulting in slower tumor growth. These results demonstrate that sIgM
      produced by B cells can upregulate the functions of MDSCs in tumor-bearing mice
      to aggravate cancer progression. In a mouse model of CLL, production of secretory
      IgM led to more MDSCs, fewer T cells, and shorter survival times for the mice.
      Thus, secretory IgM may aggravate the progression of this cancer. Cancer Immunol
      Res; 6(6); 696-710. (c)2018 AACR.

PMID- 29650520
TI  - Alarming underutilisation of rehabilitation in athletes with anterior cruciate
      ligament reconstruction: four ways to change the game.

PMID- 29650521
TI  - Infographic. The effect of high-speed running on hamstring strain injury risk.

PMID- 29650522
TI  - Medical schools should be prioritising nutrition and lifestyle education.

PMID- 29650523
TI  - The enigma of rotator cuff tears and the case for uncertainty.

PMID- 29650524
TI  - ERF deletion rescues RAS deficiency in mouse embryonic stem cells.
AB  - MEK inhibition in combination with a glycogen synthase kinase-3beta (GSK3beta)
      inhibitor, referred as the 2i condition, favors pluripotency in embryonic stem
      cells (ESCs). However, the mechanisms by which the 2i condition limits ESC
      differentiation and whether RAS proteins are involved in this phenomenon remain
      poorly understood. Here we show that RAS nullyzygosity reduces the growth of
      mouse ESCs (mESCs) and prohibits their differentiation. Upon RAS deficiency or
      MEK inhibition, ERF (E twenty-six 2 [Ets2]-repressive factor), a transcriptional
      repressor from the ETS domain family, translocates to the nucleus, where it binds
      to the enhancers of pluripotency factors and key RAS targets. Remarkably,
      deletion of Erf rescues the proliferative defects of RAS-devoid mESCs and
      restores their capacity to differentiate. Furthermore, we show that Erf loss
      enables the development of RAS nullyzygous teratomas. In summary, this work
      reveals an essential role for RAS proteins in pluripotency and identifies ERF as
      a key mediator of the response to RAS/MEK/ERK inhibition in mESCs.

PMID- 29650525
TI  - Flushing Disorders Associated with Gastrointestinal Symptoms: Part 1,
      Neuroendocrine Tumors, Mast Cell Disorders and Hyperbasophila.
AB  - Flushing is the subjective sensation of warmth accompanied by visible cutaneous
      erythema occurring throughout the body with a predilection for the face, neck,
      pinnae, and upper trunk where the skin is thinnest and cutaneous vessels are
      superficially located and in greatest numbers. Flushing can be present in either
      a wet or dry form depending upon whether neural-mediated mechanisms are involved.
      Activation of the sympathetic nervous system results in wet flushing, accompanied
      by diaphoresis, due to concomitant stimulation of eccrine sweat glands. Wet
      flushing is caused by certain medications, panic disorder and paroxysmal extreme
      pain disorder (PEPD). Vasodilator mediated flushing due to the formation and
      release of a variety of biogenic amines, neuropeptides and phospholipid mediators
      such as histamine, serotonin and prostaglandins, respectively, typically presents
      as dry flushing where sweating is characteristically absent. Flushing occurring
      with neuroendocrine tumors accompanied by gastrointestinal symptoms is generally
      of the dry flushing variant, which may be an important clinical clue to the
      differential diagnosis. A number of primary diseases of the gastrointestinal
      tract cause flushing, and conversely extra-intestinal conditions are associated
      with flushing and gastrointestinal symptoms. Gastrointestinal findings vary and
      include one or more of the following non-specific symptoms such as abdominal
      pain, nausea, vomiting, diarrhea or constipation. The purpose of this review is
      to provide a focused comprehensive discussion on the presentation,
      pathophysiology, diagnostic evaluation and management of those diseases that
      arise from the gastrointestinal tract or other site that may cause
      gastrointestinal symptoms secondarily accompanied by flushing. This review is
      divided into two parts given the scope of conditions that cause flushing and
      affect the gastrointestinal tract: Part 1 covers neuroendocrine tumors
      (carcinoid, pheochromocytomas, vasoactive intestinal polypeptide, medullary
      carcinoma of the thyroid), polyneuropathy, organomegaly, endocrinopathy,
      monoclonal protein, skin changes (POEMS), and conditions involving mast cells and
      basophils; while Part 2 covers dumping syndrome, mesenteric traction syndrome,
      rosacea, hyperthyroidism and thyroid storm, anaphylaxis, panic disorders,
      paroxysmal extreme pain disorder, and food, alcohol and medications.

PMID- 29650527
TI  - Brief guided parent-delivered CBT is both efficacious andcost-effective for
      childhood anxiety disorders.

PMID- 29650526
TI  - Flushing Disorders Associated with Gastrointestinal Symptoms: Part 2, Systemic
      Miscellaneous Conditions.
AB  - Flushing disorders with involvement of the gastrointestinal tract represent a
      heterogeneous group of conditions. In part 1 of this review series,
      neuroendocrine tumors (NET), mast cell activation disorders (MCAD), and
      hyperbasophilia were discussed. In this section we discuss the remaining flushing
      disorders which primarily or secondarily involve the gastrointestinal tract. This
      includes dumping syndrome, mesenteric traction syndrome, rosacea, hyperthyroidism
      and thyroid storm, anaphylaxis, panic disorders, paroxysmal extreme pain
      disorder, and food, alcohol and medications. With the exception of paroxysmal
      pain disorders, panic disorders and some medications, these disorders presents
      with dry flushing. A detailed and comprehensive family, social, medical and
      surgical history, as well as recognizing the presence of other systemic symptoms
      are important in distinguishing the different disease that cause flushing with
      gastrointestinal symptoms.

PMID- 29650529
TI  - Put science first and formatting later.

PMID- 29650528
TI  - Practical guide to the meta-analysis of rare events.
AB  - OBJECTIVE: Meta-analysing studies with low event rates is challenging as some of
      the standard methods for meta-analysis are not well suited to handle rare
      outcomes. This is more evident when some studies have zero events in one or both
      treatment groups. In this article, we discuss why rare events require special
      attention in meta-analysis, we present an overview of some approaches suitable
      for meta-analysing rare events and we provide practical recommendations for their
      use. METHODS: We go through several models suggested in the literature for
      performing a rare events meta-analysis, highlighting their respective advantages
      and limitations. We illustrate these models using a published example from mental
      health. We provide the software code needed to perform all analyses in the
      appendix. RESULTS: Different methods may give different results, and using a
      suboptimal approach may lead to erroneous conclusions. When data are very sparse,
      the choice between the available methods may have a large impact on the results.
      Methods that use the so-called continuity correction (eg, adding 0.5 to the
      number of events and non-events in studies with zero events in one treatment
      group) may lead to biased estimates. CONCLUSIONS: Researchers should define the
      primary analysis a priori, in order to avoid selective reporting. A sensitivity
      analysis using a range of methods should be used to assess the robustness of
      results. Suboptimal methods such as using a continuity correction should be
      avoided.

PMID- 29650530
TI  - Synthetic gene drive: between continuity and novelty: Crucial differences between
      gene drive and genetically modified organisms require an adapted risk assessment
      for their use.

PMID- 29650532
TI  - Tumor Cells Metastasize from Lymph Nodes.
AB  - Two mouse studies have found that tumor cells can metastasize via the lymph
      nodes. One study demonstrated that cancer cells from lymph-node metastases
      accounted for most cells in lung metastases. The other study found that tumor
      cells can spread from the lymph nodes to the lungs by entering the bloodstream.

PMID- 29650531
TI  - beta-catenin-activated hepatocellular carcinomas are addicted to fatty acids.
AB  - OBJECTIVES: CTNNB1-mutated hepatocellular carcinomas (HCCs) constitute a major
      part of human HCC and are largely inaccessible to target therapy. Yet, little is
      known about the metabolic reprogramming induced by beta-catenin oncogenic
      activation in the liver. We aimed to decipher such reprogramming and assess
      whether it may represent a new avenue for targeted therapy of CTNNB1-mutated HCC.
      DESIGN: We used mice with hepatocyte-specific oncogenic activation of beta
      catenin to evaluate metabolic reprogramming using metabolic fluxes on tumourous
      explants and primary hepatocytes. We assess the role of Pparalpha in knock-out
      mice and analysed the consequences of fatty acid oxidation (FAO) using etomoxir.
      We explored the expression of the FAO pathway in an annotated human HCC dataset.
      RESULTS: beta-catenin-activated HCC were not glycolytic but intensively oxidised
      fatty acids. We found that Pparalpha is a beta-catenin target involved in FAO
      metabolic reprograming. Deletion of Pparalpha was sufficient to block the
      initiation and progression of beta-catenin-dependent HCC development. FAO was
      also enriched in human CTNNB1-mutated HCC, under the control of the transcription
      factor PPARalpha. CONCLUSIONS: FAO induced by beta-catenin oncogenic activation
      in the liver is the driving force of the beta-catenin-induced HCC. Inhibiting FAO
      by genetic and pharmacological approaches blocks HCC development, showing that
      inhibition of FAO is a suitable therapeutic approach for CTNNB1-mutated HCC.

PMID- 29650533
TI  - Early-Career Scientists Advocate for Funding on Capitol Hill.
AB  - Congress recently approved a $3 billion NIH budget increase for fiscal year 2018,
      the third year of a significant increase after a period of flat or declining
      funding, but early-career scientists deciding whether to pursue a career in
      research need stable, long-term funding over many years. Some of these
      investigators traveled to Capitol Hill last month and met with members of
      Congress and their staffs to advocate for sustainable, reliable government
      research funding.

PMID- 29650535
TI  - WNKs on the Fly.

PMID- 29650534
TI  - Sequential ALK Inhibitors Can Select for Lorlatinib-Resistant Compound ALK
      Mutations in ALK-Positive Lung Cancer.
AB  - The cornerstone of treatment for advanced ALK-positive lung cancer is sequential
      therapy with increasingly potent and selective ALK inhibitors. The third
      generation ALK inhibitor lorlatinib has demonstrated clinical activity in
      patients who failed previous ALK inhibitors. To define the spectrum of ALK
      mutations that confer lorlatinib resistance, we performed accelerated mutagenesis
      screening of Ba/F3 cells expressing EML4-ALK. Under comparable conditions, N
      ethyl-N-nitrosourea (ENU) mutagenesis generated numerous crizotinib-resistant but
      no lorlatinib-resistant clones harboring single ALK mutations. In similar screens
      with EML4-ALK containing single ALK resistance mutations, numerous lorlatinib
      resistant clones emerged harboring compound ALK mutations. To determine the
      clinical relevance of these mutations, we analyzed repeat biopsies from
      lorlatinib-resistant patients. Seven of 20 samples (35%) harbored compound ALK
      mutations, including two identified in the ENU screen. Whole-exome sequencing in
      three cases confirmed the stepwise accumulation of ALK mutations during
      sequential treatment. These results suggest that sequential ALK inhibitors can
      foster the emergence of compound ALK mutations, identification of which is
      critical to informing drug design and developing effective therapeutic
      strategies.Significance: Treatment with sequential first-, second-, and third
      generation ALK inhibitors can select for compound ALK mutations that confer high
      level resistance to ALK-targeted therapies. A more efficacious long-term strategy
      may be up-front treatment with a third-generation ALK inhibitor to prevent the
      emergence of on-target resistance. Cancer Discov; 8(6); 714-29. (c)2018 AACR.This
      article is highlighted in the In This Issue feature, p. 663.

PMID- 29650536
TI  - Repairing the GBM Step by Step.

PMID- 29650537
TI  - The Quest for Better Biomarkers of Bone Turnover in CKD.

PMID- 29650538
TI  - Kir Channel Blockages by Proflavine Derivatives via Multiple Modes of
      Interaction.
AB  - Many compounds inhibit tetrameric and pseudo-tetrameric cation channels by
      associating with the central cavity located in the middle of the membrane plane.
      They traverse the ion conduction pathway from the intracellular side and through
      access to the cavity. Previously, we reported that the bacteriostatic agent,
      proflavine, preferentially blocked a subset of inward rectifier K+ (Kir)
      channels. However, the development of the inhibition of Kir1.1 by the compound
      was obviously different from that operating in Kir3.2 as a pore blocker. To gain
      mechanistic insights into the compound-channel interaction, we analyzed its
      chemical specificity, subunit selectivity, and voltage dependency using 13
      different combinations of Kir-channel family members and 11 proflavine
      derivatives. The Kir-channel family members were classified into three groups: 1)
      Kir2.2, Kir3.x, Kir4.2, and Kir6.2Delta36, which exhibited Kir3.2-type inhibition
      (slow onset and recovery, irreversible, and voltage-dependent blockage); 2)
      Kir1.1 and Kir4.1/Kir5.1 (prompt onset and recovery, reversible, and voltage
      independent blockage); and 3) Kir2.1, Kir2.3, Kir4.1, and Kir7.1 (no response).
      The degree of current inhibition depended on the combination of compounds and
      channels. Chimera between proflavine-sensitive Kir1.1 and -insensitive Kir4.1
      revealed that the extracellular portion of Kir1.1 is crucial for the recognition
      of the proflavine derivative acrinol. In conclusion, preferential blockage of Kir
      channel family members by proflavine derivatives is based on multiple modes of
      action. This raises the possibility of designing subunit-specific inhibitors.

PMID- 29650539
TI  - A call for more science in forensic science.
AB  - Forensic science is critical to the administration of justice. The discipline of
      forensic science is remarkably complex and includes methodologies ranging from
      DNA analysis to chemical composition to pattern recognition. Many forensic
      practices developed under the auspices of law enforcement and were vetted
      primarily by the legal system rather than being subjected to scientific scrutiny
      and empirical testing. Beginning in the 1990s, exonerations based on DNA-related
      methods revealed problems with some forensic disciplines, leading to calls for
      major reforms. This process generated a National Academy of Science report in
      2009 that was highly critical of many forensic practices and eventually led to
      the establishment of the National Commission for Forensic Science (NCFS) in 2013.
      The NCFS was a deliberative body that catalyzed communication between nonforensic
      scientists, forensic scientists, and other stakeholders in the legal community.
      In 2017, despite continuing problems with forensic science, the Department of
      Justice terminated the NCFS. Just when forensic science needs the most support,
      it is getting the least. We urge the larger scientific community to come to the
      aid of our forensic colleagues by advocating for urgently needed research,
      testing, and financial support.

PMID- 29650541
TI  - FDA places "unique" restrictions on contraceptive implant Essure.

PMID- 29650540
TI  - Next-Generation Sequencing of the Complete Mitochondrial Genome of the Endangered
      Species Black Lion Tamarin Leontopithecus chrysopygus (Primates) and Mitogenomic
      Phylogeny Focusing on the Callitrichidae Family.
AB  - We describe the complete mitochondrial genome sequence of the Black Lion Tamarin,
      an endangered primate species endemic to the Atlantic Rainforest of Brazil. We
      assembled the Leontopithecus chrysopygus mitogenome, through analysis of 523M
      base pairs (bp) of short reads produced by next-generation sequencing (NGS) on
      the Illumina Platform, and investigated the presence of nuclear mitochondrial
      pseudogenes and heteroplasmic sites. Additionally, we conducted phylogenetic
      analyses using all complete mitogenomes available for primates until June 2017.
      The single circular mitogenome of BLT showed organization and arrangement that
      are typical for other vertebrate species, with a total of 16618 bp, containing 13
      protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and 1 non
      coding region (D-loop region). Our full phylogenetic tree is based on the most
      comprehensive mitogenomic dataset for Callitrichidae species to date, adding new
      data for the Leontopithecus genus, and discussing previous studies performed on
      primates. Moreover, the mitochondrial genome reported here consists of a robust
      mitogenome with 3000X coverage, which certainly will be useful for further
      phylogenetic and evolutionary analyses of Callitrichidae and higher taxa.

PMID- 29650542
TI  - An incidental finding on a knee radiograph.

PMID- 29650543
TI  - RBM20 Mutations Induce an Arrhythmogenic Dilated Cardiomyopathy Related to
      Disturbed Calcium Handling.
AB  - BACKGROUND: Mutations in RBM20 (RNA-binding motif protein 20) cause a clinically
      aggressive form of dilated cardiomyopathy, with an increased risk of malignant
      ventricular arrhythmias. RBM20 is a splicing factor that targets multiple pivotal
      cardiac genes, such as Titin (TTN) and CAMK2D (calcium/calmodulin-dependent
      kinase II delta). Aberrant TTN splicing is thought to be the main determinant of
      RBM20-induced dilated cardiomyopathy, but is not likely to explain the increased
      risk of arrhythmias. Here, we investigated the extent to which RBM20 mutation
      carriers have an increased risk of arrhythmias and explore the underlying
      molecular mechanism. METHODS: We compared clinical characteristics of RBM20 and
      TTN mutation carriers and used our previously generated Rbm20 knockout (KO) mice
      to investigate downstream effects of Rbm20-dependent splicing. Cellular
      electrophysiology and Ca2+ measurements were performed on isolated cardiomyocytes
      from Rbm20 KO mice to determine the intracellular consequences of reduced Rbm20
      levels. RESULTS: Sustained ventricular arrhythmias were more frequent in human
      RBM20 mutation carriers than in TTN mutation carriers (44% versus 5%,
      respectively, P=0.006). Splicing events that affected Ca2+- and ion-handling
      genes were enriched in Rbm20 KO mice, most notably in the genes CamkIIdelta and
      RyR2. Aberrant splicing of CamkIIdelta in Rbm20 KO mice resulted in a remarkable
      shift of CamkIIdelta toward the delta-A isoform that is known to activate the L
      type Ca2+ current ( ICa,L). In line with this, we found an increased ICa,L,
      intracellular Ca2+ overload and increased sarcoplasmic reticulum Ca2+ content in
      Rbm20 KO myocytes. In addition, not only complete loss of Rbm20, but also
      heterozygous loss of Rbm20 increased spontaneous sarcoplasmic reticulum Ca2+
      releases, which could be attenuated by treatment with the ICa,L antagonist
      verapamil. CONCLUSIONS: We show that loss of Rbm20 disturbs Ca2+ handling and
      leads to more proarrhythmic Ca2+ releases from the sarcoplasmic reticulum.
      Patients that carry a pathogenic RBM20 mutation have more ventricular arrhythmias
      despite a similar left ventricular function, in comparison with patients with a
      TTN mutation. Our experimental data suggest that RBM20 mutation carriers may
      benefit from treatment with an ICa,L blocker to reduce their arrhythmia burden.

PMID- 29650544
TI  - Evaluation and Management of Right-Sided Heart Failure: A Scientific Statement
      From the American Heart Association.
AB  - BACKGROUND AND PURPOSE: The diverse causes of right-sided heart failure (RHF)
      include, among others, primary cardiomyopathies with right ventricular (RV)
      involvement, RV ischemia and infarction, volume loading caused by cardiac lesions
      associated with congenital heart disease and valvular pathologies, and pressure
      loading resulting from pulmonic stenosis or pulmonary hypertension from a variety
      of causes, including left-sided heart disease. Progressive RV dysfunction in
      these disease states is associated with increased morbidity and mortality. The
      purpose of this scientific statement is to provide guidance on the assessment and
      management of RHF. 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 September 2017. The document is organized and classified
      according to the American Heart Association to provide specific suggestions,
      considerations, or reference to contemporary clinical practice recommendations.
      RESULTS: Chronic RHF is associated with decreased exercise tolerance, poor
      functional capacity, decreased cardiac output and progressive end-organ damage
      (caused by a combination of end-organ venous congestion and underperfusion), and
      cachexia resulting from poor absorption of nutrients, as well as a systemic
      proinflammatory state. It is the principal cause of death in patients with
      pulmonary arterial hypertension. Similarly, acute RHF is associated with
      hemodynamic instability and is the primary cause of death in patients presenting
      with massive pulmonary embolism, RV myocardial infarction, and postcardiotomy
      shock associated with cardiac surgery. Functional assessment of the right side of
      the heart can be hindered by its complex geometry. Multiple hemodynamic and
      biochemical markers are associated with worsening RHF and can serve to guide
      clinical assessment and therapeutic decision making. Pharmacological and
      mechanical interventions targeting isolated acute and chronic RHF have not been
      well investigated. Specific therapies promoting stabilization and recovery of RV
      function are lacking. CONCLUSIONS: RHF is a complex syndrome including diverse
      causes, pathways, and pathological processes. In this scientific statement, we
      review the causes and epidemiology of RV dysfunction and the pathophysiology of
      acute and chronic RHF and provide guidance for the management of the associated
      conditions leading to and caused by RHF.

PMID- 29650546
TI  - Aortic Stenosis: Then and Now.

PMID- 29650545
TI  - Regulation of Blood Pressure by Targeting CaV1.2-Galectin-1 Protein Interaction.
AB  - BACKGROUND: L-type CaV1.2 channels play crucial roles in the regulation of blood
      pressure. Galectin-1 (Gal-1) has been reported to bind to the I-II loop of CaV1.2
      channels to reduce their current density. However, the mechanistic understanding
      for the downregulation of CaV1.2 channels by Gal-1 and whether Gal-1 plays a
      direct role in blood pressure regulation remain unclear. METHODS: In vitro
      experiments involving coimmunoprecipitation, Western blot, patch-clamp
      recordings, immunohistochemistry, and pressure myography were used to evaluate
      the molecular mechanisms by which Gal-1 downregulates CaV1.2 channel in
      transfected, human embryonic kidney 293 cells, smooth muscle cells, arteries from
      Lgasl1-/- mice, rat, and human patients. In vivo experiments involving the
      delivery of Tat-e9c peptide and AAV5-Gal-1 into rats were performed to
      investigate the effect of targeting CaV1.2-Gal-1 interaction on blood pressure
      monitored by tail-cuff or telemetry methods. RESULTS: Our study reveals that Gal
      1 is a key regulator for proteasomal degradation of CaV1.2 channels. Gal-1
      competed allosterically with the CaVbeta subunit for binding to the I-II loop of
      the CaV1.2 channel. This competitive disruption of CaVbeta binding led to CaV1.2
      degradation by exposing the channels to polyubiquitination. It is notable that we
      demonstrated that the inverse relationship of reduced Gal-1 and increased CaV1.2
      protein levels in arteries was associated with hypertension in hypertensive rats
      and patients, and Gal-1 deficiency induces higher blood pressure in mice because
      of the upregulated CaV1.2 protein level in arteries. To directly regulate blood
      pressure by targeting the CaV1.2-Gal-1 interaction, we administered Tat-e9c, a
      peptide that competed for binding of Gal-1 by a miniosmotic pump, and this
      specific disruption of CaV1.2-Gal-1 coupling increased smooth muscle CaV1.2
      currents, induced larger arterial contraction, and caused hypertension in rats.
      In contrasting experiments, overexpression of Gal-1 in smooth muscle by a single
      bolus of AAV5-Gal-1 significantly reduced blood pressure in spontaneously
      hypertensive rats. CONCLUSIONS: We have defined molecularly that Gal-1 promotes
      CaV1.2 degradation by replacing CaVbeta and thereby exposing specific lysines for
      polyubiquitination and by masking I-II loop endoplasmic reticulum export signals.
      This mechanistic understanding provided the basis for targeting CaV1.2-Gal-1
      interaction to demonstrate clearly the modulatory role that Gal-1 plays in
      regulating blood pressure, and offering a potential approach for therapeutic
      management of hypertension.

PMID- 29650547
TI  - In vivo growth of 60 non-screening detected lung cancers: a computed tomography
      study.
AB  - Current pulmonary nodule management guidelines are based on nodule volume
      doubling time, which assumes exponential growth behaviour. However, this is a
      theory that has never been validated in vivo in the routine-care target
      population. This study evaluates growth patterns of untreated solid and subsolid
      lung cancers of various histologies in a non-screening setting.Growth behaviour
      of pathology-proven lung cancers from two academic centres that were imaged at
      least three times before diagnosis (n=60) was analysed using dedicated software.
      Random-intercept random-slope mixed-models analysis was applied to test which
      growth pattern most accurately described lung cancer growth. Individual growth
      curves were plotted per pathology subgroup and nodule type.We confirmed that
      growth in both subsolid and solid lung cancers is best explained by an
      exponential model. However, subsolid lesions generally progress slower than solid
      ones. Baseline lesion volume was not related to growth, indicating that smaller
      lesions do not grow slower compared to larger ones.By showing that lung cancer
      conforms to exponential growth we provide the first experimental basis in the
      routine-care setting for the assumption made in volume doubling time analysis.

PMID- 29650548
TI  - To track or not to track: wheeze phenotypes in preschool children.

PMID- 29650549
TI  - The disease model: implications for clinical practice.

PMID- 29650550
TI  - Chronic breathlessness: re-thinking the symptom.

PMID- 29650552
TI  - Hackathons as a means of accelerating scientific discoveries and knowledge
      transfer.
AB  - Scientific research plays a key role in the advancement of human knowledge and
      pursuit of solutions to important societal challenges. Typically, research occurs
      within specific institutions where data are generated and subsequently analyzed.
      Although collaborative science bringing together multiple institutions is now
      common, in such collaborations the analytical processing of the data is often
      performed by individual researchers within the team, with only limited internal
      oversight and critical analysis of the workflow prior to publication. Here, we
      show how hackathons can be a means of enhancing collaborative science by enabling
      peer review before results of analyses are published by cross-validating the
      design of studies or underlying data sets and by driving reproducibility of
      scientific analyses. Traditionally, in data analysis processes, data generators
      and bioinformaticians are divided and do not collaborate on analyzing the data.
      Hackathons are a good strategy to build bridges over the traditional divide and
      are potentially a great agile extension to the more structured collaborations
      between multiple investigators and institutions.

PMID- 29650551
TI  - HNRNPA1 promotes recognition of splice site decoys by U2AF2 in vivo.
AB  - Alternative pre-mRNA splicing plays a major role in expanding the transcript
      output of human genes. This process is regulated, in part, by the interplay of
      trans-acting RNA binding proteins (RBPs) with myriad cis-regulatory elements
      scattered throughout pre-mRNAs. These molecular recognition events are critical
      for defining the protein-coding sequences (exons) within pre-mRNAs and directing
      spliceosome assembly on noncoding regions (introns). One of the earliest events
      in this process is recognition of the 3' splice site (3'ss) by U2 small nuclear
      RNA auxiliary factor 2 (U2AF2). Splicing regulators, such as the heterogeneous
      nuclear ribonucleoprotein A1 (HNRNPA1), influence spliceosome assembly both in
      vitro and in vivo, but their mechanisms of action remain poorly described on a
      global scale. HNRNPA1 also promotes proofreading of 3'ss sequences though a
      direct interaction with the U2AF heterodimer. To determine how HNRNPA1 regulates
      U2AF-RNA interactions in vivo, we analyzed U2AF2 RNA binding specificity using
      individual-nucleotide resolution crosslinking immunoprecipitation (iCLIP) in
      control and HNRNPA1 overexpression cells. We observed changes in the distribution
      of U2AF2 crosslinking sites relative to the 3'ss of alternative cassette exons
      but not constitutive exons upon HNRNPA1 overexpression. A subset of these events
      shows a concomitant increase of U2AF2 crosslinking at distal intronic regions,
      suggesting a shift of U2AF2 to "decoy" binding sites. Of the many noncanonical
      U2AF2 binding sites, Alu-derived RNA sequences represented one of the most
      abundant classes of HNRNPA1-dependent decoys. We propose that one way HNRNPA1
      regulates exon definition is to modulate the interaction of U2AF2 with decoy or
      bona fide 3'ss.

PMID- 29650554
TI  - Pulmonary alveolar proteinosis and Mycobacterium abscessus lung infection related
      to ruxolitinib after allogeneic stem cell transplantation.

PMID- 29650555
TI  - Noninfectious lung complications after allogeneic haematopoietic stem cell
      transplantation.
AB  - Epidemiological data on late-onset noninfectious pulmonary complications
      (LONIPCs) following allogeneic haematopoietic stem cell transplantation (HSCT)
      are derived exclusively from retrospective studies and are conflicting. We aimed
      to evaluate prospectively the incidence, risk factors and outcomes for
      LONIPCs.All consecutive patients scheduled to receive allogeneic HSCT between
      2006 and 2008 at a university teaching hospital in France were screened for
      inclusion in the study. Eligible patients were those surviving at day 100. Among
      243 screened patients, 198 patients were included in the analysis. The median
      (interquartile range) follow-up was 72.3 (15.2-88.5) months. 55 LONIPCs were
      diagnosed in 43 patients. Bronchiolitis obliterans syndrome (n=22) and
      interstitial lung disease (n=12) were the most common LONIPCs. At 36 months after
      inclusion, the estimated cumulative incidence of LONIPCs was 19.8% (95% CI 14.2
      25.3%). The estimated median survival after the diagnosis of LONIPCs was 78.5
      months (95% CI 20.0-not reached). Based on a multivariate Cox model, a history of
      chest irradiation anytime prior to HSCT, a history of pneumonia within 100 days
      post-HSCT and a low mean forced expiratory flow at 25-75% of forced vital
      capacity at day 100 were associated with the development of LONIPCs.Our data
      provide clues to identify patients at high risk of developing LONIPCs. These
      patients should be targeted for close monitoring to provide earlier LONIPC
      treatment or prophylactic treatment.

PMID- 29650553
TI  - Enduring epigenetic landmarks define the cancer microenvironment.
AB  - The growth and progression of solid tumors involves dynamic cross-talk between
      cancer epithelium and the surrounding microenvironment. To date, molecular
      profiling has largely been restricted to the epithelial component of tumors;
      therefore, features underpinning the persistent protumorigenic phenotype of the
      tumor microenvironment are unknown. Using whole-genome bisulfite sequencing, we
      show for the first time that cancer-associated fibroblasts (CAFs) from localized
      prostate cancer display remarkably distinct and enduring genome-wide changes in
      DNA methylation, significantly at enhancers and promoters, compared to
      nonmalignant prostate fibroblasts (NPFs). Differentially methylated regions
      associated with changes in gene expression have cancer-related functions and
      accurately distinguish CAFs from NPFs. Remarkably, a subset of changes is shared
      with prostate cancer epithelial cells, revealing the new concept of tumor
      specific epigenome modifications in the tumor and its microenvironment. The
      distinct methylome of CAFs provides a novel epigenetic hallmark of the cancer
      microenvironment and promises new biomarkers to improve interpretation of
      diagnostic samples.

PMID- 29650556
TI  - Early experience with delamanid-containing regimens in the treatment of
      complicated multidrug-resistant tuberculosis in Hong Kong.

PMID- 29650557
TI  - Sputum proteomics and airway cell transcripts of current and ex-smokers with
      severe asthma in U-BIOPRED: an exploratory analysis.
AB  - Severe asthma patients with a significant smoking history have airflow
      obstruction with reported neutrophilia. We hypothesise that multi-omic analysis
      will enable the definition of smoking and ex-smoking severe asthma molecular
      phenotypes.The U-BIOPRED cohort of severe asthma patients, containing current
      smokers (CSA), ex-smokers (ESA), nonsmokers and healthy nonsmokers was examined.
      Blood and sputum cell counts, fractional exhaled nitric oxide and spirometry were
      obtained. Exploratory proteomic analysis of sputum supernatants and
      transcriptomic analysis of bronchial brushings, biopsies and sputum cells was
      performed.Colony-stimulating factor (CSF)2 protein levels were increased in CSA
      sputum supernatants, with azurocidin 1, neutrophil elastase and CXCL8 upregulated
      in ESA. Phagocytosis and innate immune pathways were associated with neutrophilic
      inflammation in ESA. Gene set variation analysis of bronchial epithelial cell
      transcriptome from CSA showed enrichment of xenobiotic metabolism, oxidative
      stress and endoplasmic reticulum stress compared to other groups. CXCL5 and
      matrix metallopeptidase 12 genes were upregulated in ESA and the epithelial
      protective genes, mucin 2 and cystatin SN, were downregulated.Despite little
      difference in clinical characteristics, CSA were distinguishable from ESA
      subjects at the sputum proteomic level, with CSA patients having increased CSF2
      expression and ESA patients showing sustained loss of epithelial barrier
      processes.

PMID- 29650559
TI  - Care in Chronic Obstructive Lung Disease (CAROL): a randomised trial in general
      practice.
AB  - Disease management of chronic obstructive pulmonary disease (COPD) is complex and
      shortcomings in general practice care for COPD are common. A care bundle is a
      disease management aid used as a reminder and for steering specific elements of
      care. Our objectives were to test whether a COPD care bundle delivered to general
      practitioners (GPs) and practice assistants increases the implementation of key
      elements of COPD care.The study was a cluster-randomised clinical trial, with 1:1
      randomisation of GPs and a 1-year follow-up. The intervention introduced a COPD
      care bundle and aimed at enhancing collaboration between GPs and practice
      assistants. The control group continued usual care. The primary outcome measure
      was the composite score from nine key elements of COPD care measured at the
      patient level.We enrolled 35 GPs and 216 patients with a median age of 69 years,
      59% female, 69% Global Initiative for Chronic Obstructive Lung Disease group A or
      B. After 1 year, the between-group difference in change of the primary outcome
      measure was +2.2 (95% CI +1.5- +2.9) in favour of the intervention group. The
      intervention was associated with significantly higher implementation rates in
      seven out of nine key elements of care.Disease management using a COPD care
      bundle increased the implementation of key elements of COPD care in general
      practice.

PMID- 29650560
TI  - Countrywide implementation of whole genome sequencing: an opportunity to improve
      tuberculosis management, surveillance and contact tracing in low incidence
      countries.

PMID- 29650558
TI  - Low-dose computed tomography for the diagnosis of pneumonia in elderly patients:
      a prospective, interventional cohort study.
AB  - The diagnosis of pneumonia is challenging. Our objective was to assess whether
      low-dose computed tomography (LDCT) modified the probability of diagnosing
      pneumonia in elderly patients.We prospectively included patients aged over 65
      years with a suspicion of pneumonia treated with antimicrobial therapy (AT). All
      patients had a chest radiograph and LDCT within 72 h of inclusion. The treating
      clinician assessed the probability of pneumonia before and after the LDCT scan
      using a Likert scale. An adjudication committee retrospectively rated the
      probability of pneumonia and was considered as the reference for diagnosis. The
      main outcome was the difference in the clinician's pneumonia probability
      estimates before and after LDCT and the proportion of modified diagnoses which
      matched the reference diagnosis (the net reclassification improvement (NRI)).A
      total of 200 patients with a median age of 84 years were included. After LDCT,
      the estimated probability of pneumonia changed in 90 patients (45%), of which 60
      (30%) were downgraded and 30 (15%) were upgraded. The NRI was 8% (NRI event (-6%)
      + NRI non-event (14%)).LDCT modified the estimated probability of pneumonia in a
      substantial proportion of patients. It mostly helped to exclude a diagnosis of
      pneumonia and hence to reduce unnecessary AT.

PMID- 29650561
TI  - Meta-analysis of airway epithelium gene expression in asthma.
AB  - Differential gene expression in the airway epithelium of patients with asthma
      versus controls has been reported in several studies. However, there is no
      consensus on which genes are reproducibly affected in asthma. We sought to
      identify a consensus list of differentially expressed genes (DEGs) using a meta
      analysis approach.We identified eight studies with data that met defined
      inclusion criteria. These studies comprised 355 cases and 193 controls and
      involved sampling either bronchial or nasal epithelium. We conducted study-level
      analyses, followed by a meta-analysis. Likewise, we applied a meta-analysis
      framework to the results of study-level pathway enrichment.We identified 1273
      DEGs, 431 of which had not been identified in previous studies. 450 DEGs
      exhibited large effect sizes and were robust to study population differences in
      age, sex, race/ethnicity, medication use, smoking status and exacerbations. The
      magnitude of differential expression of these 450 genes was highly similar in
      bronchial and nasal airway epithelia. Meta-analysis of pathway enrichment
      revealed a number of consistently dysregulated biological pathways, including
      putative transcriptional and post-transcriptional regulators.In total, we
      identified a set of genes that is consistently dysregulated in asthma, that links
      to known and novel biological pathways, and that will inform asthma subtype
      identification.

PMID- 29650562
TI  - The outcome of severe varicella pneumonia with respiratory failure admitted to
      the intensive care unit for mechanical ventilation.

PMID- 29650564
TI  - What is the minimal clinically important difference for helium-3 magnetic
      resonance imaging ventilation defects?

PMID- 29650563
TI  - Blood eosinophil count and risk of pneumonia hospitalisations in individuals with
      COPD.
AB  - Blood eosinophil count in chronic obstructive pulmonary disease (COPD) is
      associated with higher exacerbation rate and favourable response to
      corticosteroids; however, frequent exacerbations and use of inhaled
      corticosteroids could elevate pneumonia risk. We tested the hypothesis that high
      blood eosinophil counts are associated with high risk of pneumonia in individuals
      with severe COPD from the general population.We included 7180 individuals with
      COPD from the Copenhagen General Population Study, including 643 with forced
      expiratory volume in 1 s (FEV1) <50% predicted between 2003 and 2011. All primary
      discharge diagnoses of pneumonia during follow-up were recorded.Among individuals
      with COPD and FEV1 <50% pred, the multivariable adjusted incidence rate ratio was
      2.17 (95% CI 1.31-3.58) for pneumonia comparing individuals with blood eosinophil
      counts >=0.34*109 cells.L-1versus <0.34*109 cells.L-1 In individuals with
      clinical COPD, defined by recent exacerbation, >=10 pack-years of smoking and
      FEV1 <70% pred, the corresponding risk was 4.52 (2.11-9.72). Risk of pneumonia
      did not differ by blood eosinophil count in individuals with COPD and FEV1 >=50%
      pred.In individuals with COPD and FEV1 <50% pred, blood eosinophil count
      >=0.34*109 cells.L-1 was associated with high risk of hospitalisation due to
      pneumonia.

PMID- 29650565
TI  - Complete Coding Sequences of Dengue Virus Type 2 Strains from Febrile Patients
      Seen in Malindi District Hospital, Kenya, during the 2017 Dengue Fever Outbreak.
AB  - We report here 10 complete polyprotein-coding sequences of dengue virus type 2
      strains isolated from febrile patients who presented at Malindi District
      Hospital, Kenya, during a recent dengue fever outbreak. Phylogenetically, all the
      strains belonged to clonal serotype 2 of the Cosmopolitan genotype.

PMID- 29650566
TI  - Genome Sequences of Ilzat and Eleri, Two Phages Isolated Using Microbacterium
      foliorum NRRL B-24224.
AB  - Bacteriophages Ilzat and Eleri are newly isolated Siphoviridae infecting
      Microbacterium foliorum NRRL B-24224. The phage genomes are similar in length,
      G+C content, and architecture and share 62.9% nucleotide sequence identity.

PMID- 29650567
TI  - Genome Sequence of a Multidrug-Resistant Candida haemulonii Isolate from a
      Patient with Chronic Leg Ulcers in Israel.
AB  - Candida haemulonii is an emerging multidrug-resistant yeast that can cause
      invasive candidiasis. Here, we report the first genome sequence of C. haemulonii
      (isolate B11899) generated using PacBio sequencing technology. The estimated
      genome size was 13.3 Mb, with a GC content of 45.19%.

PMID- 29650568
TI  - Genome Sequence of a Heterotrophic Nitrifier and Aerobic Denitrifier, Paracoccus
      denitrificans Strain ISTOD1, Isolated from Wastewater.
AB  - We report here the draft genome sequence of Paracoccus denitrificans strain
      ISTOD1 of 4.9 Mb, isolated from wastewater. It has been identified as a
      heterotrophic nitrifying and aerobic denitrifying bacterium. Genomic analysis
      revealed genes related to nitrogen and phosphorus removal, showing that the
      strain holds potential for bioremediation and biorefinery uses.

PMID- 29650569
TI  - Whole-Genome Sequences of Cronobacter sakazakii Isolates Obtained from Foods of
      Plant Origin and Dried-Food Manufacturing Environments.
AB  - Here, we present draft genome sequences of 29 Cronobacter sakazakii isolates
      obtained from foods of plant origin and dried-food manufacturing facilities.
      Assemblies and annotations resulted in genome sizes ranging from 4.3 to 4.5 Mb
      and 3,977 to 4,256 gene-coding sequences with G+C contents of ~57.0%.

PMID- 29650570
TI  - Draft Genome Sequence of Aeromonas lusitana sp. nov. Strain DSM 24905T, Isolated
      from a Hot Spring in Vila-Real, Portugal.
AB  - Aeromonas lusitana sp. nov. is an isolate derived from a study aimed at
      characterizing Aeromonas spp. from water sources used for recreation and
      agricultural purposes and assessing the implications these organisms have for
      human and animal health. We present here the 4.52-Mbp draft genome sequence of
      this novel species.

PMID- 29650571
TI  - Draft Genome Sequence of Aeromonas cavernicola sp. nov. DSM 24474T, Isolated from
      a Cavern Brook in the Moravia Region of the Czech Republic.
AB  - Species of the Aeromonas genus can be found in numerous environmental milieus,
      including various water sources, and some species cause disease in animals. We
      present here the draft genome sequence for Aeromonas cavernicola DSM 24474T, a
      novel species isolated from a freshwater brook within a cavern in the Czech
      Republic.

PMID- 29650572
TI  - Draft Whole-Genome Sequence of the Fluorene-Degrading Sphingobium sp. Strain
      LB126, Isolated from Polycyclic Aromatic Hydrocarbon-Contaminated Soil.
AB  - We report here the draft whole-genome sequence of a fluorene-degrading bacterium,
      Sphingobium sp. strain LB126. The genes involved in the upper biodegradation
      pathway of fluorene are located on a plasmid, and the lower pathway that
      generates tricarboxylic acid cycle intermediates is initiated by the meta
      cleavage of protocatechuic acid that is chromosomally encoded.

PMID- 29650573
TI  - Draft Genome Sequence of Pseudomonas oceani DSM 100277T, a Deep-Sea Bacterium.
AB  - Pseudomonas oceani DSM 100277T was isolated from deep seawater in the Okinawa
      Trough at 1390 m. P. oceani belongs to the Pseudomonas pertucinogena group. Here,
      we report the draft genome sequence of P. oceani, which has an estimated size of
      4.1 Mb and exhibits 3,790 coding sequences, with a G+C content of 59.94 mol%.

PMID- 29650574
TI  - Draft Genome Sequence of the Intimin-Positive Enteropathogenic Escherichia
      albertii Strain MBT-EA1, Isolated from Lettuce.
AB  - The genome of the intimin (eae)-harboring Escherichia albertii strain MBT-EA1,
      isolated from lettuce in Germany, was sequenced. Sequence analysis showed the
      assembled draft genome size to be 4,560,948 bp, containing a predicted total of
      4,414 protein-encoding genes, 11 rRNAs, and 82 tRNAs. Furthermore, three plasmid
      sequences were found.

PMID- 29650575
TI  - Genome Sequences of Five Mycobacterium bovis Strains Isolated from Farmed Animals
      and Wildlife in Canada.
AB  - Mycobacterium bovis is the causative agent of bovine tuberculosis, an infectious
      disease that affects both animals and humans and thus presents a risk to public
      health and the livestock industry. Here, we report the genome sequences of five
      Mycobacterium bovis strains that represent major genotype clusters observed in
      farmed animals and wildlife in Canada.

PMID- 29650576
TI  - Draft Genome Sequences of Four Strains of Recently Established Novel Veillonella
      Species Isolated from Human Oral Cavities.
AB  - Veillonella species are known to contribute to the formation of early oral
      biofilms and tend to be prevalent in people with poor oral hygiene status. Here,
      we report the draft genome sequences of 4 oral Veillonella strains that were
      established recently as novel species.

PMID- 29650577
TI  - Draft Genome Sequences of New Genomospecies "Candidatus Pectobacterium maceratum"
      Strains, Which Cause Soft Rot in Plants.
AB  - Investigation of collections of phytopathogenic bacteria has revealed some
      strains distinct from known Pectobacterium spp. We report here the draft genome
      sequences of five such strains, isolated during the period of 1947 to 2012. Based
      on comparative genomics, we propose a new candidate genomospecies of the genus
      Pectobacterium, "Candidatus Pectobacterium maceratum."

PMID- 29650578
TI  - Draft Genome Sequences of Three Ochrobactrum spp. Isolated from Different Avian
      Hosts in Pakistan.
AB  - Here, we present the draft genome sequences of three Ochrobactrum sp. strains
      with multidrug-resistant properties, isolated in 2015 from a pigeon and two
      chickens in Pakistan.

PMID- 29650579
TI  - Draft Genome Sequence of Raoultella ornithinolytica Strain HH3.
AB  - Raoultella ornithinolytica is a Gram-negative, nonmotile, encapsulated, and
      aerobic bacillus and an emerging hospital-related bacterial pathogen of humans.
      Here, we report a 5,977,517-bp draft genome sequence for Raoultella
      ornithinolytica strain HH3, isolated from a pretreatment sample collected at a
      Canadian wastewater treatment facility.

PMID- 29650580
TI  - High-Quality Whole-Genome Sequences for 59 Historical Shigella Strains Generated
      with PacBio Sequencing.
AB  - Shigella spp. are enteric pathogens that cause shigellosis. We report here the
      high-quality whole-genome sequences of 59 historical Shigella strains that
      represent the four species and a variety of serotypes.

PMID- 29650581
TI  - Draft Genome Sequence of the Mercury-Resistant Strain Acinetobacter baumannii
      I43.
AB  - Here, we report the draft genome sequence of the Acinetobacter baumannii strain
      I43, which is highly resistant to mercury. The Illumina-based sequence analysis
      revealed a genome of approximately 4,520,353 bp composed of 4,091 coding
      sequences.

PMID- 29650582
TI  - Draft Genome Sequences of 12 Clinical and Environmental Methicillin-Resistant
      Staphylococcus pseudintermedius Strains Isolated from a Veterinary Teaching
      Hospital in Washington State.
AB  - Methicillin-resistant Staphylococcus pseudintermedius (MRSP) is a globally
      emergent multidrug-resistant pathogen of dogs associated with nosocomial
      transmission in dogs and with potential zoonotic impacts. Here, we report the
      draft whole-genome sequences of 12 hospital-associated MRSP strains and their
      resistance genotypes and phenotypes.

PMID- 29650583
TI  - Draft Genome Sequences of Four Clinical Legionella pneumophila Isolates from
      Ontario, Canada.
AB  - Legionella pneumophila outbreak investigations require the development of
      reliable typing methods to better understand the genetic relationships of the
      isolates involved. Here, we report the draft genome sequences of four clinical
      Legionella pneumophila isolates obtained between 2000 and 2012 in Ontario,
      Canada.

PMID- 29650584
TI  - Draft Genome Sequence of Strain B 225, an Iron-Depositing Isolate of the Genus
      Novosphingobium.
AB  - Here, we report the draft genome sequence of Novosphingobium sp. strain B 225, an
      iron-depositing bacterium isolated from a phenazone-amended naturally grown
      biofilm. This biofilm was grown in the Unteres Odertal National Park, Germany.
      Illumina NextSeq sequencing was used to determine the genome of the strain.

PMID- 29650585
TI  - Draft Genomic Sequences of Chromobacterium sp. nov. Strains MWU13-2610 and MWU14
      2602, Isolated from Wild Cranberry Bogs in Massachusetts.
AB  - Chromobacterium sp. nov. strains MWU13-2610 and MWU14-2602 were isolated from
      cranberry bogs in the Cape Cod National Seashore. These nonpigmented bacteria
      represent two new presumptive species of the rapidly growing genus
      Chromobacterium Gene homologs are present for multiple antibiotic resistance,
      virulence functions, and prophages.

PMID- 29650586
TI  - First Insight into the Genome Sequence of Clostridium vincentii DSM 10228,
      Isolated from Sediment of the McMurdo Ice Shelf, Antarctica.
AB  - Clostridium vincentii is an obligate anaerobic, saccharophilic, psychrophilic,
      Gram-positive, motile, and rod-shaped bacterium. It was isolated from a pond
      sediment of the McMurdo Ice Shelf, Antarctica. C. vincentii produces acetate and
      formate as main fermentation products. The draft genome consists of one
      chromosome (3.506 Mb) with 3,379 predicted protein-encoding genes.

PMID- 29650587
TI  - Draft Genome Sequence of Actinobacterial Strain Kineosporia sp. R_H_3, a
      Neutrophilic Iron-Depositing Bacterium.
AB  - The draft genome sequence of a neutrophilic iron-depositing actinobacterial
      strain, Kineosporia sp. R_H_3, is reported here. Detailed analysis of the genome
      can elucidate the role of specific cytochromes for Fe oxidation and how this
      organism might receive energy from Fe oxidation. To date, this is the second
      publicly available genome sequence of a Kineosporia strain.

PMID- 29650588
TI  - Draft Genome Sequence of Janthinobacterium sp. Strain ROICE36, a Putative
      Secondary Metabolite-Synthesizing Bacterium Isolated from Antarctic Snow.
AB  - The draft genome assembly of Janthinobacterium sp. strain ROICE36 has 207
      contigs, with a total genome size of 5,977,006 bp and a G+C content of 62%.
      Preliminary genome analysis identified 5,363 protein-coding genes and a total of
      7 secondary metabolic gene clusters (encoding bacteriocins, nonribosomal peptide
      synthetase [NRPS], terpene, hserlactone, and other ketide synthases).

PMID- 29650589
TI  - Direct activation of chordoblasts by retinoic acid is required for segmented
      centra mineralization during zebrafish spine development.
AB  - Zebrafish mutants with increased retinoic acid (RA) signaling due to the loss of
      the RA-inactivating enzyme Cyp26b1 develop a hyper-mineralized spine with
      gradually fusing vertebral body precursors (centra). However, the underlying
      cellular mechanisms remain incompletely understood. Here, we show that cells of
      the notochord epithelium named chordoblasts are sensitive to RA signaling.
      Chordoblasts are uniformly distributed along the anteroposterior axis and
      initially generate the continuous collagenous notochord sheath. However,
      subsequently and iteratively, subsets of these cells undergo further RA-dependent
      differentiation steps, acquire a stellate-like shape, downregulate expression of
      the collagen gene col2a1a, switch on cyp26b1 expression and trigger metameric
      sheath mineralization. This mineralization fails to appear upon chordoblast
      specific cell ablation or RA signal transduction blockade. Together, our data
      reveal that, despite their different developmental origins, the activities and
      regulation of chordoblasts are very similar to those of osteoblasts, including
      their RA-induced transition from osteoid-producing cells to osteoid-mineralizing
      ones. Furthermore, our data point to a requirement for locally controlled RA
      activity within the chordoblast layer in order to generate the segmented
      vertebral column.

PMID- 29650592
TI  - Using Q-methodology to guide the implementation of new healthcare policies.
AB  - There are many challenges in the development, implementation and evaluation of
      healthcare policy. One challenge is understanding how different stakeholders view
      a particular policy and what impact these views may have during implementation. Q
      methodology is one approach that can be used to help policy makers and
      researchers actively engage with those who are important in policy
      implementation, and anticipate their responses. Q-methodology combines
      qualitative and quantitative research methods to systematically explore and
      describe the range of viewpoints about a topic. Participants are required to rank
      a set of predefined statements relating to the topic, according to their own
      viewpoint. Factor analytic techniques then identify people who are like-minded in
      the way they view the topic and enable areas of consensus and divergence in
      viewpoint to be clearly defined. This mapping of viewpoints allows those working
      in policy implementation to anticipate likely barriers and levers in implementing
      new policies.

PMID- 29650590
TI  - Coordination of meristem and boundary functions by transcription factors in the
      SHOOT MERISTEMLESS regulatory network.
AB  - The Arabidopsis homeodomain transcription factor SHOOT MERISTEMLESS (STM) is
      crucial for shoot apical meristem (SAM) function, yet the components and
      structure of the STM gene regulatory network (GRN) are largely unknown. Here, we
      show that transcriptional regulators are overrepresented among STM-regulated
      genes and, using these as GRN components in Bayesian network analysis, we infer
      STM GRN associations and reveal regulatory relationships between STM and factors
      involved in multiple aspects of SAM function. These include hormone regulation,
      TCP-mediated control of cell differentiation, AIL/PLT-mediated regulation of
      pluripotency and phyllotaxis, and specification of meristem-organ boundary zones
      via CUC1. We demonstrate a direct positive transcriptional feedback loop between
      STM and CUC1, despite their distinct expression patterns in the meristem and
      organ boundary, respectively. Our further finding that STM activates expression
      of the CUC1-targeting microRNA miR164c combined with mathematical modelling
      provides a potential solution for this apparent contradiction, demonstrating that
      these proposed regulatory interactions coupled with STM mobility could be
      sufficient to provide a mechanism for CUC1 localisation at the meristem-organ
      boundary. Our findings highlight the central role for the STM GRN in coordinating
      SAM functions.

PMID- 29650591
TI  - Ldb1- and Rnf12-dependent regulation of Lhx2 controls the relative balance
      between neurogenesis and gliogenesis in the retina.
AB  - Precise control of the relative ratio of retinal neurons and glia generated
      during development is essential for visual function. We show that Lhx2, which
      encodes a LIM-homeodomain transcription factor essential for specification and
      differentiation of retinal Muller glia, also plays a crucial role in the
      development of retinal neurons. Overexpression of Lhx2 with its transcriptional
      co-activator Ldb1 triggers cell cycle exit and inhibits both Notch signaling and
      retinal gliogenesis. Lhx2/Ldb1 overexpression also induces the formation of wide
      field amacrine cells (wfACs). In contrast, Rnf12, which encodes a negative
      regulator of LDB1, is necessary for the initiation of retinal gliogenesis. We
      also show that Lhx2-dependent neurogenesis and wfAC formation requires Ascl1 and
      Neurog2, and that Lhx2 is necessary for their expression, although overexpression
      of Lhx2/Ldb1 does not elevate expression of these proneural bHLH factors.
      Finally, we demonstrate that the relative level of the LHX2-LDB1 complex in the
      retina decreases in tandem with the onset of gliogenesis. These findings show
      that control of Lhx2 function by Ldb1 and Rnf12 underpins the coordinated
      differentiation of neurons and Muller glia in postnatal retina.

PMID- 29650593
TI  - Human Neural Stem Cell Extracellular Vesicles Improve Recovery in a Porcine Model
      of Ischemic Stroke.
AB  - BACKGROUND AND PURPOSE: Recent work from our group suggests that human neural
      stem cell-derived extracellular vesicle (NSC EV) treatment improves both tissue
      and sensorimotor function in a preclinical thromboembolic mouse model of stroke.
      In this study, NSC EVs were evaluated in a pig ischemic stroke model, where
      clinically relevant end points were used to assess recovery in a more
      translational large animal model. METHODS: Ischemic stroke was induced by
      permanent middle cerebral artery occlusion (MCAO), and either NSC EV or PBS
      treatment was administered intravenously at 2, 14, and 24 hours post-MCAO. NSC EV
      effects on tissue level recovery were evaluated via magnetic resonance imaging at
      1 and 84 days post-MCAO. Effects on functional recovery were also assessed
      through longitudinal behavior and gait analysis testing. RESULTS: NSC EV
      treatment was neuroprotective and led to significant improvements at the tissue
      and functional levels in stroked pigs. NSC EV treatment eliminated intracranial
      hemorrhage in ischemic lesions in NSC EV pigs (0 of 7) versus control pigs (7 of
      8). NSC EV-treated pigs exhibited a significant decrease in cerebral lesion
      volume and decreased brain swelling relative to control pigs 1-day post-MCAO. NSC
      EVs significantly reduced edema in treated pigs relative to control pigs, as
      assessed by improved diffusivity through apparent diffusion coefficient maps. NSC
      EVs preserved white matter integrity with increased corpus callosum fractional
      anisotropy values 84 days post-MCAO. Behavior and mobility improvements
      paralleled structural changes as NSC EV-treated pigs exhibited improved outcomes,
      including increased exploratory behavior and faster restoration of spatiotemporal
      gait parameters. CONCLUSIONS: This study demonstrated for the first time that in
      a large animal model novel NSC EVs significantly improved neural tissue
      preservation and functional levels post-MCAO, suggesting NSC EVs may be a
      paradigm changing stroke therapeutic.

PMID- 29650595
TI  - ?

PMID- 29650594
TI  - Stop invoking evidence-based data!

PMID- 29650597
TI  - Purdue's influence continues.

PMID- 29650596
TI  - Career in family medicine.

PMID- 29650598
TI  - Author's honoraria from opioid seller.

PMID- 29650599
TI  - Taking unnecessary aim at MAID.

PMID- 29650600
TI  - Cannabis view.

PMID- 29650601
TI  - Uncharted territory: Knowledge translation of competency-based continuing
      professional development in family medicine.

PMID- 29650604
TI  - Narrative-based medicine and the general practice consultation: Narrative-based
      medicine 2.
AB  - OBJECTIVE: To raise awareness of narrative-based medicine (NBM) as a valuable
      approach to the consultation, which, if practised more widely by GPs, would
      convey considerable benefits to both patient and doctor. SOURCES OF INFORMATION:
      Principally, this article draws on the perspectives of 2 of NBM's key proponents,
      John Launer and Rita Charon, and which are complemented by the perspectives of
      several other authors. MAIN MESSAGE: This article examines NBM in relation to
      patient-centred care and the particular skills that are required to practise NBM.
      Narrative-based medicine brings together skills from other fields of practice
      skills that are not beyond the capabilities of GPs-conferring benefits on patient
      and doctor. Narrative-based medicine's skills enhance the patient-centred method
      and an evidence-based approach. CONCLUSION: The literature speaks very loudly
      about the importance of narrative and of understanding the illness experience.
      What makes NBM stand out is the fact that it is a collaborative and mutually
      beneficial process, having the power to create a new narrative-a narrative that
      heals and transforms the patient and the doctor.

PMID- 29650603
TI  - Top studies relevant to primary care practice.
AB  - OBJECTIVE: To summarize 10 high-quality studies from 2017 that have strong
      relevance to primary care practice. QUALITY OF EVIDENCE: Study selection involved
      routine literature surveillance by a group of primary care health professionals.
      This included screening abstracts of important journals and Evidence Alerts, as
      well as searching the American College of Physicians Journal Club. MAIN MESSAGE:
      Topics of the 2017 articles include whether treating subclinical hypothyroidism
      improves outcomes or symptoms; whether evolocumab reduces cardiovascular disease
      as well as low-density lipoprotein levels; whether lifestyle interventions reduce
      medication use in patients with diabetes; whether vitamin D prevents
      cardiovascular disease, cancer, or upper respiratory tract infections; whether
      canagliflozin reduces clinical events in patients with diabetes; how
      corticosteroid injections affect knee osteoarthritis; whether drained abscesses
      benefit from antibiotic treatment; whether patients with diabetes benefit from
      bariatric surgery; whether exenatide reduces clinical events in patients with
      diabetes; and whether tympanostomy tubes affect outcomes in recurrent acute
      otitis media or chronic otitis media. We provide brief summaries, context where
      needed, and final recommendations for 10 studies with potential effects on
      primary care. We also briefly review 5 "runner-up" studies. CONCLUSION: Research
      from 2017 produced several high-quality studies in diabetes management. These
      have demonstrated benefit for alternative therapies and offered evidence not
      previously available. This year's selection of studies also provided information
      on a variety of conditions and therapies that are, or might become, more common
      in primary care settings.

PMID- 29650605
TI  - Facial rash in a 48-year-old woman: Case report of suspected leprosy in the
      emergency department.

PMID- 29650606
TI  - Support of caregivers of persons with dementia.

PMID- 29650607
TI  - Sulfonylurea treatment in type 2 diabetes.

PMID- 29650608
TI  - ?

PMID- 29650602
TI  - Primary care of adults with intellectual and developmental disabilities: 2018
      Canadian consensus guidelines.
AB  - OBJECTIVE: To update the 2011 Canadian guidelines for primary care of adults with
      intellectual and developmental disabilities (IDD). METHODS: Family physicians and
      other health professionals experienced in the care of people with IDD reviewed
      and synthesized recent empirical, ecosystem, expert, and experiential knowledge.
      A system was developed to grade the strength of recommendations. RECOMMENDATIONS:
      Adults with IDD are a heterogeneous group of patients and have health conditions
      and factors affecting their health that can vary in kind, manifestation,
      severity, or complexity from those of others in the community. They require
      approaches to care and interventions that are adapted to their needs. These
      guidelines provide advice regarding standards of care. References to clinical
      tools and other practical resources are incorporated. The approaches to care that
      are outlined here can be applied to other groups of patients that have
      impairments in cognitive, communicative, or other adaptive functioning.
      CONCLUSION: As primary care providers, family physicians play a vital role in
      promoting the health and well-being of adults with IDD. These guidelines can aid
      their decision making with patients and caregivers.

PMID- 29650609
TI  - Condom use to aid cervical visualization during speculum examination.

PMID- 29650610
TI  - Spring tonic.

PMID- 29650611
TI  - Teaching residents about medical assistance in dying.

PMID- 29650613
TI  - ?

PMID- 29650612
TI  - The cost of medication.

PMID- 29650614
TI  - ?

PMID- 29650615
TI  - Digital engagement.

PMID- 29650616
TI  - ?

PMID- 29650618
TI  - ?

PMID- 29650619
TI  - Nursing role in well-child care: Systematic review of the literature.
AB  - OBJECTIVE: To describe and compare well-child care (WCC) in Australia, the
      Netherlands, and the United Kingdom (UK), focusing on the role of nurses and
      their interactions with other primary care providers in order to derive relevant
      lessons for Canada's interprofessional primary care teams. DATA SOURCES: Ovid
      MEDLINE, EMBASE, and CINAHL were searched broadly using the search terms well
      child care, nursing role, and delivery of care and other synonymous terms. In
      addition, Google Scholar was used to search for gray literature, and reference
      mining revealed a few other relevant articles. STUDY SELECTION: The original
      search identified 929 articles. The inclusion criteria were the following:
      relevant to WCC delivery; focuses on Canada, the Netherlands, the UK, Australia,
      or an international comparison; describes care of healthy term infants; describes
      care provided in the community; and describes the role of the nurse in WCC
      delivery. An abstract review followed by full-text review condensed the search to
      25 selected articles. SYNTHESIS: Selected articles varied in method and scope;
      thus, a narrative synthesis was generated using thematic analysis. In Australia,
      the Netherlands, and the UK, many WCC tasks are performed by trained public
      health nurses in a separate but parallel system to family medicine, with
      interaction between nurses and FPs varying greatly among countries. In general,
      nurses' roles in WCC remained in the preventive care and screening domains,
      including monitoring development, providing health education, and supporting
      parents. The 3 overarching themes that were identified were around professional
      development and education, integration of care and interprofessional
      collaboration, and the nurses' role in an evolving health system. CONCLUSION:
      International examples, given Canada's primary care reforms, suggest it is time
      to examine greater role sharing in WCC between nurses and FPs in
      interdisciplinary primary care teams.

PMID- 29650620
TI  - Relationship between income and mortality in a Canadian family practice cohort.
AB  - OBJECTIVE: To examine the relationship between household income and mortality in
      a primary care cohort while using personal information obtained from clinical
      records and administrative data linkages to adjust for confounders. DESIGN:
      Survey and analysis of data from several administrative databases. SETTING:
      Toronto, Ont. PARTICIPANTS: Patients of an urban academic family practice who
      were aged between 45 and 74 and who had made at least 3 visits to the clinic
      between 1996 and 1997. MAIN OUTCOME MEASURES: Patients' self-reported household
      income. Patients' personal information obtained from clinical records and
      linkages to administrative data to adjust for confounders; personal information
      was used to adjust for health factors as confounders of the relationship between
      income and mortality risk. RESULTS: Of the 1064 patients who received surveys,
      519 (49%) responded. There was no significant difference in the mortality rate
      between nonresponders and responders. Mortality rates were lower than those in
      the general population throughout follow-up. Within the patient cohort, mortality
      rates were elevated for smokers, those who had not consumed alcohol in the year
      before the survey, and those who had been diagnosed with diabetes, hypertension,
      or cancer before the survey. After all adjustments were made, mortality rates
      were lower among patients in the higher-income categories than among those with
      lower household incomes. CONCLUSION: Universal health care does not eliminate
      income-related differentials in mortality. Differences in health-related
      behaviour factors are not sufficient to explain the socioeconomic mortality
      differences within an area. These data suggest that it is not solely personal
      choice related to health behaviour but that other explanations must be invoked to
      account for the relationship between lower household income and increased
      mortality rates.

PMID- 29650617
TI  - ?

PMID- 29650622
TI  - ?

PMID- 29650621
TI  - Barriers to and enablers of advance care planning with patients in primary care:
      Survey of health care providers.
AB  - OBJECTIVE: To identify barriers to and enablers of advance care planning (ACP)
      perceived by physicians and other health professionals in primary care. DESIGN:
      Cross-sectional, self-administered survey. SETTING: Ontario, Alberta, and British
      Columbia. PARTICIPANTS: Family physicians (n = 117) and other health
      professionals (n = 64) in primary care. MAIN OUTCOME MEASURES: Perceived barriers
      relating to the clinician, characteristics of patients, and system factors, rated
      on a 7-point scale from 0 (not at all) to 6 (an extreme amount), and enablers
      reported using an open-ended question. RESULTS: Between November 2014 and June
      2015, questionnaires were returned by 72.2% (117 of 162) of family physicians and
      68.8% (64 of 93) of the other health professionals. Physicians rated insufficient
      time, inability to electronically transfer the advance care plan across care
      settings, decreased interaction with patients near the end of life owing to
      transfer of care, and patients' difficulty understanding limitations and
      complications of treatment options as the highest barriers. Other health
      professionals additionally identified their own lack of knowledge and difficulty
      accessing the physician as barriers. Themes identified as enablers included
      greater public engagement, clinician attitudes, creating capacity for clinicians,
      integrating ACP into practice, and system and policy supports. CONCLUSION: In
      primary care, there are barriers to engaging patients in ACP at the patient,
      provider, and system levels that could potentially be addressed through the
      informed development of multifaceted interventions.

PMID- 29650623
TI  - Meet the First Authors.

PMID- 29650624
TI  - Does a Newly Characterized Cell From the Bone Marrow Repair the Heart After Acute
      Myocardial Infarction?

PMID- 29650625
TI  - It's the Metabolism That Makes Macrophages Detectable in the Magnetic Resonance
      Scanner: Immune Cell Detection by Hyperpolarized 13C Magnetic Resonance Imaging.

PMID- 29650626
TI  - Infarct Size Reduction by Targeting Ischemic Injury: Back to Square One.

PMID- 29650627
TI  - Rajat Gupta: A Scientist in Doctor's Clothing.

PMID- 29650628
TI  - Liberation From the P Value's Tyranny.

PMID- 29650629
TI  - Critical Evaluation of Data Requires Rigorous but Broadly Based Statistical
      Inference.

PMID- 29650630
TI  - Is Optimism Associated With Healthier Cardiovascular-Related Behavior? Meta
      Analyses of 3 Health Behaviors.
AB  - Optimistic people have reduced risk for cardiovascular disease and cardiovascular
      related mortality compared with their less optimistic peers. One explanation for
      this is that optimistic people may be more likely to engage in healthy behavior
      like exercising frequently, eating fruits and vegetables, and avoiding cigarette
      smoking. However, researchers have not formally determined the extent or
      direction of optimism's association with health behaviors. Moreover, it is
      unclear whether optimism temporally precedes health behaviors or whether the
      relationship is because of shared common causes. We conducted random effects meta
      analyses examining optimism's association with 3 health behaviors relevant for
      the prevention of cardiovascular disease. PubMed and PsycINFO databases were
      searched for studies published through November 2017 reporting on optimism's
      relationship with physical activity, diet, and cigarette smoking. We identified
      34 effect sizes for physical activity (n=90 845), 15 effect sizes for diet (n=47
      931), and 15 effect sizes for cigarette smoking (n=15 052). Findings suggested
      that more optimistic individuals tended to engage in healthier behaviors compared
      with less optimistic individuals, but effect sizes were modest (ractivity=0.07,
      P<0.0001; rdiet=0.12, P<0.0001; and rsmoking=0.07, P=0.001). Most evidence was
      cross-sectional (>=53% of effect sizes) and did not consider sociodemographic
      characteristics (<53% of effect sizes) or psychological distress (<27% of effect
      sizes) as potential confounders. Optimism is associated with healthier behaviors
      that protect against cardiovascular disease, although most evidence was
      relatively low quality. Additional longitudinal and experimental research is
      required to determine whether optimism causally contributes to healthy behaviors
      and whether optimism could be an effective target for preventing cardiovascular
      disease.

PMID- 29650633
TI  - Letter by Scarabin-Carre and Scarabin Regarding Article, "Associations of
      Endogenous Estradiol and Testosterone Levels With Plaque Composition and Risk of
      Stroke in Subjects With Carotid Atherosclerosis".

PMID- 29650634
TI  - Response by Glisic et al to Letter Regarding Article, "Associations of Endogenous
      Estradiol and Testosterone Levels With Plaque Composition and Risk of Stroke in
      Subjects With Carotid Atherosclerosis".

PMID- 29650635
TI  - Letter by De Meyer Regarding Article, "Short Leukocyte Telomere Length Precedes
      Clinical Expression of Atherosclerosis: The Blood-and-Muscle Model".

PMID- 29650631
TI  - The Vasculature in Prediabetes.
AB  - The frequency of prediabetes is increasing as the prevalence of obesity rises
      worldwide. In prediabetes, hyperglycemia, insulin resistance, and inflammation
      and metabolic derangements associated with concomitant obesity cause endothelial
      vasodilator and fibrinolytic dysfunction, leading to increased risk of
      cardiovascular and renal disease. Importantly, the microvasculature affects
      insulin sensitivity by affecting the delivery of insulin and glucose to skeletal
      muscle; thus, endothelial dysfunction and extracellular matrix remodeling promote
      the progression from prediabetes to diabetes mellitus. Weight loss is the
      mainstay of treatment in prediabetes, but therapies that improved endothelial
      function and vasodilation may not only prevent cardiovascular disease but also
      slow progression to diabetes mellitus.

PMID- 29650636
TI  - Response by Benetos et al to Letter Regarding Article, "Short Leukocyte Telomere
      Length Precedes Clinical Expression of Atherosclerosis: The Blood-and-Muscle
      Model".

PMID- 29650637
TI  - Cerebral fat embolism: the value of susceptibility-weighted imaging.

PMID- 29650632
TI  - Mechanisms of Cardiac Repair and Regeneration.
AB  - Cardiovascular regenerative therapies are pursued on both basic and translational
      levels. Although efficacy and value of cell therapy for myocardial regeneration
      can be debated, there is a consensus that profound deficits in mechanistic
      understanding limit advances, optimization, and implementation. In collaboration
      with the TACTICS (Transnational Alliance for Regenerative Therapies in
      Cardiovascular Syndromes), this review overviews several pivotal aspects of
      biological processes impinging on cardiac maintenance, repair, and regeneration.
      The goal of summarizing current mechanistic understanding is to prompt innovative
      directions for fundamental studies delineating cellular reparative and
      regenerative processes. Empowering myocardial regenerative interventions, whether
      dependent on endogenous processes or exogenously delivered repair agents,
      ultimately depends on mastering mechanisms and novel strategies that take
      advantage of rather than being limited by inherent myocardial biology.

PMID- 29650638
TI  - Actinomyces cavernous sinus infection: a case and systematic literature review.
AB  - A 63-year-old man presented with a 2-month history of progressive right-sided
      exophthalmos, painful ophthalmoplegia and fevers. As more features developed, he
      was diagnosed with giant cell arteritis, then Tolosa-Hunt syndrome, and
      transiently responded to corticosteroids. A bland cerebrospinal fluid and highly
      metabolically active brain (18F)-fluoro-D-glucose-positron emission tomography
      suggested lymphoma. Biopsy of the mass showed sulphur granules with Gram-positive
      filamentous bacteria with Actinomyces-like colonies. Actinomyces cavernous sinus
      infections are rare and indolent. They often mimic non-infective causes including
      other inflammatory and infiltrative conditions, vascular and neoplastic causes,
      particularly lymphoma. Clinicians should consider infective cavernous sinus
      syndromes in people with a fluctuating painful ophthalmoplegia that responds
      poorly to corticosteroids. The term Tolosa-Hunt syndrome is problematic and
      should be retired or used only with reservation.

PMID- 29650639
TI  - Non-convulsive status epilepticus: mimics and chameleons.
AB  - Non-convulsive status epilepticus (NCSE) is an enigmatic condition with protean
      manifestations. It often goes unrecognised, leading to delays in its diagnosis
      and treatment. The principal reason for such delay is the failure to consider and
      request an electroencephalogram (EEG), although occasional presentations have no
      scalp or surface electroencephalographic correlate. In certain settings with
      limited EEG availability, particularly out-of-hours, clinicians should consider
      treating without an EEG. Patients need a careful risk-benefit analysis to assess
      the risks of neuronal damage and harm versus the risks of adverse effects from
      various intensities of therapeutic intervention. Specialists in EEG, intensive
      care or epilepsy are invaluable in the management of patients with possible NCSE.

PMID- 29650640
TI  - [18F]Florbetaben PET-CT confirms AL amyloidosis in a patient with Waldenstrom's
      Macroglobulinemia.

PMID- 29650641
TI  - Anti-PD1 associated fulminant myocarditis after a single pembrolizumab dose: the
      role of occult pre-existing autoimmunity.

PMID- 29650643
TI  - Correction: Mortality in idiopathic inflammatory myopathy: results from a Swedish
      nationwide population-based cohort study.

PMID- 29650642
TI  - Setd2 regulates quiescence and differentiation of adult hematopoietic stem cells
      by restricting RNA polymerase II elongation.
AB  - SET domain containing 2 (Setd2), encoding a histone methyltransferase, is
      associated with many hematopoietic diseases when mutated. By generating a novel
      exon 6 conditional knockout mouse model, we describe an essential role of Setd2
      in maintaining the adult hematopoietic stem cells. Loss of Setd2 results in
      leukopenia, anemia, and increased platelets accompanied by hypocellularity,
      erythroid dysplasia, and mild fibrosis in bone marrow. Setd2 knockout mice show
      significantly decreased hematopoietic stem and progenitor cells except for
      erythroid progenitors. Setd2 knockout hematopoietic stem cells fail to establish
      long-term bone marrow reconstitution after transplantation because of the loss of
      quiescence, increased apoptosis, and reduced multiple-lineage terminal
      differentiation potential. Bioinformatic analysis revealed that the hematopoietic
      stem cells exit from quiescence and commit to differentiation, which lead to
      hematopoietic stem cell exhaustion. Mechanistically, we attribute an important
      Setd2 function in murine adult hematopoietic stem cells to the inhibition of the
      Nsd1/2/3 transcriptional complex, which recruits super elongation complex and
      controls RNA polymerase II elongation on a subset of target genes, including Myc
      Our results reveal a critical role of Setd2 in regulating quiescence and
      differentiation of hematopoietic stem cells through restricting the NSDs/SEC
      mediated RNA polymerase II elongation.

PMID- 29650644
TI  - Correction: Repeated administration of dapirolizumab pegol in a randomised phase
      I study is well tolerated and accompanied by improvements in several composite
      measures of systemic lupus erythematosus disease activity and changes in whole
      blood transcriptomic profiles.

PMID- 29650646
TI  - Erratum for the Report "Predicting reaction performance in C-N cross-coupling
      using machine learning" by D. T. Ahneman, J. G. Estrada, S. Lin, S. D. Dreher, A.
      G. Doyle.

PMID- 29650645
TI  - MitoCPR-A surveillance pathway that protects mitochondria in response to protein
      import stress.
AB  - Mitochondrial functions are essential for cell viability and rely on protein
      import into the organelle. Various disease and stress conditions can lead to
      mitochondrial import defects. We found that inhibition of mitochondrial import in
      budding yeast activated a surveillance mechanism, mitoCPR, that improved
      mitochondrial import and protected mitochondria during import stress. mitoCPR
      induced expression of Cis1, which associated with the mitochondrial translocase
      to reduce the accumulation of mitochondrial precursor proteins at the
      mitochondrial translocase. Clearance of precursor proteins depended on the Cis1
      interacting AAA+ adenosine triphosphatase Msp1 and the proteasome, suggesting
      that Cis1 facilitates degradation of unimported proteins. mitoCPR was required
      for maintaining mitochondrial functions when protein import was compromised,
      demonstrating the importance of mitoCPR in protecting the mitochondrial
      compartment.

PMID- 29650648
TI  - News at a glance.

PMID- 29650647
TI  - Obfuscating with transparency.

PMID- 29650649
TI  - Latin America's lost histories revealed.

PMID- 29650650
TI  - Alpha Centauri's siren call has frustrated planet hunters.

PMID- 29650651
TI  - Chemists seek antiaddiction drugs to battle hijacked brain.

PMID- 29650652
TI  - Ancient sites savaged in Yemen, Iraq.

PMID- 29650653
TI  - Study questions animal efficacy data behind trials.

PMID- 29650655
TI  - Free agents.

PMID- 29650654
TI  - Human mutation rate a legacy from our past.

PMID- 29650656
TI  - How cleaner air changes the climate.

PMID- 29650657
TI  - Improved memory devices for synthetic cells.

PMID- 29650658
TI  - Redemption for self-reactive antibodies.

PMID- 29650659
TI  - Crowdsourced genealogies and genomes.

PMID- 29650660
TI  - A recipe for nanoporous graphene.

PMID- 29650661
TI  - Stephen Hawking (1942-2018).

PMID- 29650662
TI  - John Sulston (1942-2018).

PMID- 29650663
TI  - Bystander risk, social value, and ethics of human research.

PMID- 29650664
TI  - Editor's note.

PMID- 29650665
TI  - Social media for social change in science.

PMID- 29650666
TI  - Journal editors should not divide scientists.

PMID- 29650667
TI  - SciComm speaks.

PMID- 29650668
TI  - Efforts large and small speed science reform.

PMID- 29650669
TI  - Measurement of the fine-structure constant as a test of the Standard Model.
AB  - Measurements of the fine-structure constant alpha require methods from across
      subfields and are thus powerful tests of the consistency of theory and experiment
      in physics. Using the recoil frequency of cesium-133 atoms in a matter-wave
      interferometer, we recorded the most accurate measurement of the fine-structure
      constant to date: alpha = 1/137.035999046(27) at 2.0 * 10-10 accuracy. Using
      multiphoton interactions (Bragg diffraction and Bloch oscillations), we
      demonstrate the largest phase (12 million radians) of any Ramsey-Borde
      interferometer and control systematic effects at a level of 0.12 part per
      billion. Comparison with Penning trap measurements of the electron gyromagnetic
      anomaly ge - 2 via the Standard Model of particle physics is now limited by the
      uncertainty in ge - 2; a 2.5sigma tension rejects dark photons as the reason for
      the unexplained part of the muon's magnetic moment at a 99% confidence level.
      Implications for dark-sector candidates and electron substructure may be a sign
      of physics beyond the Standard Model that warrants further investigation.

PMID- 29650670
TI  - A blueprint for demonstrating quantum supremacy with superconducting qubits.
AB  - A key step toward demonstrating a quantum system that can address difficult
      problems in physics and chemistry will be performing a computation beyond the
      capabilities of any classical computer, thus achieving so-called quantum
      supremacy. In this study, we used nine superconducting qubits to demonstrate a
      promising path toward quantum supremacy. By individually tuning the qubit
      parameters, we were able to generate thousands of distinct Hamiltonian evolutions
      and probe the output probabilities. The measured probabilities obey a universal
      distribution, consistent with uniformly sampling the full Hilbert space. As the
      number of qubits increases, the system continues to explore the exponentially
      growing number of states. Extending these results to a system of 50 qubits has
      the potential to address scientific questions that are beyond the capabilities of
      any classical computer.

PMID- 29650671
TI  - Bottom-up synthesis of multifunctional nanoporous graphene.
AB  - Nanosize pores can turn semimetallic graphene into a semiconductor and, from
      being impermeable, into the most efficient molecular-sieve membrane. However,
      scaling the pores down to the nanometer, while fulfilling the tight structural
      constraints imposed by applications, represents an enormous challenge for present
      top-down strategies. Here we report a bottom-up method to synthesize nanoporous
      graphene comprising an ordered array of pores separated by ribbons, which can be
      tuned down to the 1-nanometer range. The size, density, morphology, and chemical
      composition of the pores are defined with atomic precision by the design of the
      molecular precursors. Our electronic characterization further reveals a highly
      anisotropic electronic structure, where orthogonal one-dimensional electronic
      bands with an energy gap of ~1 electron volt coexist with confined pore states,
      making the nanoporous graphene a highly versatile semiconductor for simultaneous
      sieving and electrical sensing of molecular species.

PMID- 29650673
TI  - Microbial oxidation of lithospheric organic carbon in rapidly eroding tropical
      mountain soils.
AB  - Lithospheric organic carbon ("petrogenic"; OCpetro) is oxidized during exhumation
      and subsequent erosion of mountain ranges. This process is a considerable source
      of carbon dioxide (CO2) to the atmosphere over geologic time scales, but the
      mechanisms that govern oxidation rates in mountain landscapes are poorly
      constrained. We demonstrate that, on average, 67 +/- 11% of the OCpetro initially
      present in bedrock exhumed from the tropical, rapidly eroding Central Range of
      Taiwan is oxidized in soils, leading to CO2 emissions of 6.1 to 18.6 metric tons
      of carbon per square kilometer per year. The molecular and isotopic evolution of
      bulk OC and lipid biomarkers during soil formation reveals that OCpetro
      remineralization is microbially mediated. Rapid oxidation in mountain soils
      drives CO2 emission fluxes that increase with erosion rate, thereby counteracting
      CO2 drawdown by silicate weathering and biospheric OC burial.

PMID- 29650672
TI  - Tropism for tuft cells determines immune promotion of norovirus pathogenesis.
AB  - Complex interactions between host immunity and the microbiome regulate norovirus
      infection. However, the mechanism of host immune promotion of enteric virus
      infection remains obscure. The cellular tropism of noroviruses is also unknown.
      Recently, we identified CD300lf as a murine norovirus (MNoV) receptor. In this
      study, we have shown that tuft cells, a rare type of intestinal epithelial cell,
      express CD300lf and are the target cell for MNoV in the mouse intestine. We found
      that type 2 cytokines, which induce tuft cell proliferation, promote MNoV
      infection in vivo. These cytokines can replace the effect of commensal microbiota
      in promoting virus infection. Our work thus provides insight into how the immune
      system and microbes can coordinately promote enteric viral infection.

PMID- 29650675
TI  - My path to contentment.

PMID- 29650676
TI  - Sodium bicarbonate loading limits tubular cast formation independent of
      glomerular injury and proteinuria in Dahl salt-sensitive rats.
AB  - Sodium bicarbonate (NaHCO3) slows the decline in kidney function in patients with
      chronic kidney disease (CKD), yet the mechanisms mediating this effect remain
      unclear. The Dahl salt-sensitive (SS) rat develops hypertension and progressive
      renal injury when fed a high salt diet; however, the effect of alkali loading on
      kidney injury has never been investigated in this model. We hypothesized that
      NaHCO3 protects from the development of renal injury in Dahl salt-sensitive rats
      via luminal alkalization which limits the formation of tubular casts, which are a
      prominent pathological feature in this model. To examine this hypothesis, we
      determined blood pressure and renal injury responses in Dahl SS rats drinking
      vehicle (0.1 M NaCl) or NaHCO3 (0.1 M) solutions as well as in Dahl SS rats
      lacking the voltage-gated proton channel (Hv1). We found that oral NaHCO3 reduced
      tubular NH4+ production, tubular cast formation, and interstitial fibrosis in
      rats fed a high salt diet for 2 weeks. This effect was independent of changes in
      blood pressure, glomerular injury, or proteinuria and did not associate with
      changes in renal inflammatory status. We found that null mutation of Hv1 also
      limited cast formation in Dahl SS rats independent of proteinuria or glomerular
      injury. As Hv1 is localized to the luminal membrane of TAL, our data suggest that
      alkalization of the luminal fluid within this segment limits cast formation in
      this model. Reduced cast formation, secondary to luminal alkalization within TAL
      segments may mediate some of the protective effects of alkali loading observed in
      CKD patients.

PMID- 29650674
TI  - Germinal center antibody mutation trajectories are determined by rapid
      self/foreign discrimination.
AB  - Antibodies have the specificity to differentiate foreign antigens that mimic self
      antigens, but it remains unclear how such specificity is acquired. In a mouse
      model, we generated B cells displaying an antibody that cross-reacts with two
      related protein antigens expressed on self versus foreign cells. B cell anergy
      was imposed by self antigen but reversed upon challenge with high-density foreign
      antigen, leading to germinal center recruitment and antibody gene hypermutation.
      Single-cell analysis detected rapid selection for mutations that decrease self
      affinity and slower selection for epistatic mutations that specifically increase
      foreign affinity. Crystal structures revealed that these mutations exploited
      subtle topological differences to achieve 5000-fold preferential binding to
      foreign over self epitopes. Resolution of antigenic mimicry drove the optimal
      affinity maturation trajectory, highlighting the value of retaining self-reactive
      clones as substrates for protective antibody responses.

PMID- 29650677
TI  - Eye-opening Etiologies.

PMID- 29650679
TI  - Real-time observation of flexible domain movements in CRISPR-Cas9.
AB  - The CRISPR-associated protein Cas9 is widely used for genome editing because it
      cleaves target DNA through the assistance of a single-guide RNA (sgRNA).
      Structural studies have revealed the multi-domain architecture of Cas9 and
      suggested sequential domain movements of Cas9 upon binding to the sgRNA and the
      target DNA These studies also hinted at the flexibility between domains; however,
      it remains unclear whether these flexible movements occur in solution. Here, we
      directly observed dynamic fluctuations of multiple Cas9 domains, using single
      molecule FRET We found that the flexible domain movements allow Cas9 to adopt
      transient conformations beyond those captured in the crystal structures.
      Importantly, the HNH nuclease domain only accessed the DNA cleavage position
      during such flexible movements, suggesting the importance of this flexibility in
      the DNA cleavage process. Our FRET data also revealed the conformational
      flexibility of apo-Cas9, which may play a role in the assembly with the sgRNA
      Collectively, our results highlight the potential role of domain fluctuations in
      driving Cas9-catalyzed DNA cleavage.

PMID- 29650678
TI  - Structure-function analysis of Sua5 protein reveals novel functional motifs
      required for the biosynthesis of the universal t6A tRNA modification.
AB  - N6-threonyl-carbamoyl adenosine (t6A) is a universal tRNA modification found at
      position 37, next to the anticodon, in almost all tRNAs decoding ANN codons
      (where N = A, U, G, or C). t6A stabilizes the codon-anticodon interaction and
      hence promotes translation fidelity. The first step of the biosynthesis of t6A,
      the production of threonyl-carbamoyl adenylate (TC-AMP), is catalyzed by the
      Sua5/TsaC family of enzymes. While TsaC is a single domain protein, Sua5 enzymes
      are composed of the TsaC-like domain, a linker and an extra domain called SUA5 of
      unknown function. In the present study, we report structure-function analysis of
      Pyrococcus abyssi Sua5 (Pa-Sua5). Crystallographic data revealed binding sites
      for bicarbonate substrate and pyrophosphate product. The linker of Pa-Sua5 forms
      a loop structure that folds into the active site gorge and closes it. Using
      structure-guided mutational analysis, we established that the conserved sequence
      motifs in the linker and the domain-domain interface are essential for the
      function of Pa-Sua5. We propose that the linker participates actively in the
      biosynthesis of TC-AMP by binding to ATP/PPi and by stabilizing the N-carboxy-l
      threonine intermediate. Hence, TsaC orthologs which lack such a linker and SUA5
      domain use a different mechanism for TC-AMP synthesis.

PMID- 29650680
TI  - Cell type-specific regulation of ciliary transition zone assembly in vertebrates.
AB  - Ciliopathies are life-threatening human diseases caused by defective cilia. They
      can often be traced back to mutations of genes encoding transition zone (TZ)
      proteins demonstrating that the understanding of TZ organisation is of paramount
      importance. The TZ consists of multimeric protein modules that are subject to a
      stringent assembly hierarchy. Previous reports place Rpgrip1l at the top of the
      TZ assembly hierarchy in Caenorhabditis elegans By performing quantitative
      immunofluorescence studies in RPGRIP1L-/- mouse embryos and human embryonic
      cells, we recognise a different situation in vertebrates in which Rpgrip1l
      deficiency affects TZ assembly in a cell type-specific manner. In cell types in
      which the loss of Rpgrip1l alone does not affect all modules, additional
      truncation or removal of vertebrate-specific Rpgrip1 results in an impairment of
      all modules. Consequently, Rpgrip1l and Rpgrip1 synergistically ensure the TZ
      composition in several vertebrate cell types, revealing a higher complexity of TZ
      assembly in vertebrates than in invertebrates.

PMID- 29650681
TI  - dNTP metabolism links mechanical cues and YAP/TAZ to cell growth and oncogene
      induced senescence.
AB  - YAP/TAZ, downstream transducers of the Hippo pathway, are powerful regulators of
      cancer growth. How these factors control proliferation remains poorly defined.
      Here, we found that YAP/TAZ directly regulate expression of key enzymes involved
      in deoxynucleotide biosynthesis and maintain dNTP precursor pools in human cancer
      cells. Regulation of deoxynucleotide metabolism is required for YAP-induced cell
      growth and underlies the resistance of YAP-addicted cells to chemotherapeutics
      targeting dNTP synthesis. During RAS-induced senescence, YAP/TAZ bypass RAS
      mediated inhibition of nucleotide metabolism and control senescence. Endogenous
      YAP/TAZ targets and signatures are inhibited by RAS/MEK1 during senescence, and
      depletion of YAP/TAZ is sufficient to cause senescence-associated phenotypes,
      suggesting a role for YAP/TAZ in suppression of senescence. Finally, mechanical
      cues, such as ECM stiffness and cell geometry, regulate senescence in a YAP
      dependent manner. This study indicates that YAP/TAZ couples cell proliferation
      with a metabolism suited for DNA replication and facilitates escape from oncogene
      induced senescence. We speculate that this activity might be relevant during the
      initial phases of tumour progression or during experimental stem cell
      reprogramming induced by YAP.

PMID- 29650682
TI  - Phosphoproteome dynamics during mitotic exit in budding yeast.
AB  - The cell division cycle culminates in mitosis when two daughter cells are born.
      As cyclin-dependent kinase (Cdk) activity reaches its peak, the anaphase
      promoting complex/cyclosome (APC/C) is activated to trigger sister chromatid
      separation and mitotic spindle elongation, followed by spindle disassembly and
      cytokinesis. Degradation of mitotic cyclins and activation of Cdk-counteracting
      phosphatases are thought to cause protein dephosphorylation to control these
      sequential events. Here, we use budding yeast to analyze phosphorylation dynamics
      of 3,456 phosphosites on 1,101 proteins with high temporal resolution as cells
      progress synchronously through mitosis. This reveals that successive inactivation
      of S and M phase Cdks and of the mitotic kinase Polo contributes to order these
      dephosphorylation events. Unexpectedly, we detect as many new phosphorylation
      events as there are dephosphorylation events. These correlate with late mitotic
      kinase activation and identify numerous candidate targets of these kinases. These
      findings revise our view of mitotic exit and portray it as a dynamic process in
      which a range of mitotic kinases contribute to order both protein
      dephosphorylation and phosphorylation.

PMID- 29650683
TI  - FDA Approval Summary: Mylotarg for Treatment of Patients with Relapsed or
      Refractory CD33-Positive Acute Myeloid Leukemia.
AB  - : On September 2, 2017, the U.S. Food and Drug Administration approved gemtuzumab
      ozogamicin (GO; Mylotarg; Pfizer, New York City, NY) for treatment of relapsed or
      refractory (R/R) CD33-positive acute myeloid leukemia (AML) in patients 2 years
      of age and older. GO is a CD33-directed antibody drug conjugate linked to the
      cytotoxic antibiotic calicheamicin. It originally received accelerated approval
      for treatment of older patients with relapsed CD33-positive AML in 2000, but it
      was withdrawn from the market in 2010 when the confirmatory trial failed to
      demonstrate clinical benefit among safety concerns, such as a higher rate of
      induction fatalities on the GO combination arm compared with chemotherapy alone.
      In addition, GO was associated with hepatic veno-occlusive disease (VOD), which
      has substantial morbidity and mortality. Pharmacokinetic analyses suggested a
      lower maximum concentration of GO would result in less VOD without affecting
      target saturation or efficacy. A meta-analysis across dose schedules of GO in
      patients with R/R AML showed that a lower-dose "fractionated" schedule of 3 mg/m2
      days 1, 4, and 7 was associated with less early mortality, hemorrhage, and VOD,
      without an apparent decrease in complete remission (CR) rate. MyloFrance 1 was a
      single-arm study evaluating response rates in patients with relapsed CD33
      positive AML treated with the lower-dose fractionated GO regimen. The CR rate was
      26% (95% confidence interval 16%-40%). Common adverse reactions were fever,
      infections, nausea, vomiting, constipation, bleeding, increased liver enzymes,
      and mucositis. There were no cases of VOD. These results supported the approval
      of GO as monotherapy for R/R CD33-positive AML using the lower-dose fractionated
      regimen. IMPLICATIONS FOR PRACTICE: Gemtuzumab ozogamicin (GO) 3 mg/m2 days 1, 4,
      and 7 is an active regimen for induction of remission when used to treat patients
      with relapsed or refractory CD33-positive acute myeloid leukemia without curative
      intent. The risks of hepatic veno-occlusive disease and early mortality with this
      regimen appear to be lower than reported previously for GO 9 mg/m2 days 1 and 15.
      The data were not sufficient to enable conclusions about the safety of GO in
      children younger than 2 years of age.

PMID- 29650684
TI  - Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors for Central Nervous
      System Metastases from Non-Small Cell Lung Cancer.
AB  - : Central nervous system (CNS) metastases are a common complication in patients
      with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer
      (NSCLC), resulting in a poor prognosis and limited treatment options. Treatment
      of CNS metastases requires a multidisciplinary approach, and the optimal
      treatment options and sequence of therapies are yet to be established. Many
      systemic therapies have poor efficacy in the CNS due to the challenges of
      crossing the blood-brain barrier (BBB), creating a major unmet need for the
      development of agents with good BBB-penetrating biopharmaceutical properties.
      Although the CNS penetration of first- and second-generation EGFR tyrosine kinase
      inhibitors (TKIs) is generally low, EGFR-TKI treatment has been shown to delay
      time to CNS progression in patients with CNS metastases from EGFR-mutated
      disease. However, a major challenge with EGFR-TKI treatment for patients with
      NSCLC is the development of acquired resistance, which occurs in most patients
      treated with a first-line EGFR-TKI. Novel EGFR-TKIs, such as osimertinib, have
      been specifically designed to address the challenges of acquired resistance and
      poor BBB permeability and have demonstrated efficacy in the CNS. A rational,
      iterative drug development process to design agents that could penetrate the BBB
      could prevent morbidity and mortality associated with CNS disease progression. To
      ensure a consistent approach to evaluating CNS efficacy, special consideration
      also needs to be given to clinical trial endpoints. IMPLICATIONS FOR PRACTICE:
      Historically, treatment options for patients who develop central nervous system
      (CNS) metastases have been limited and associated with poor outcomes. The
      development of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors
      (TKIs) has improved outcomes for patients with EGFR-mutated disease, and emerging
      data have demonstrated the ability of these drugs to cross the blood-brain
      barrier and elicit significant intracranial responses. Recent studies have
      indicated a role for next-generation EGFR-TKIs, such as osimertinib, in the
      treatment of CNS metastases. In the context of an evolving treatment paradigm,
      treatment should be individualized to the patient and requires a
      multidisciplinary approach.

PMID- 29650685
TI  - Osimertinib: A Novel Dermatologic Adverse Event Profile in Patients with Lung
      Cancer.
AB  - : Dermatologic adverse events (dAEs) are common with the use of epidermal growth
      factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy. First- and second
      generation agents (erlotinib, gefitinib, and afatinib) are frequently associated
      with acneiform rash, pruritus, xerosis, and paronychia; the incidence and
      characterization of these dAEs have been well described. However, there is
      evidence that the dAE profile is different with third-generation EGFR-TKIs.
      Herein, we describe the dAEs associated with third-generation EGFR-TKIs and our
      clinical experience with osimertinib, a third-generation EGFR-TKI approved by the
      U.S. Food and Drug Administration for the treatment of metastatic, EGFR T790M
      mutation-positive non-small cell lung cancer in patients whose disease has
      progressed on or after EGFR-TKI therapy. Case summaries of patients from two of
      our institutions who received osimertinib and were referred to a dermatologist
      for dAEs are also presented. Overall, the evidence suggests that osimertinib is
      associated with less severe and less frequent dAEs than first- and second
      generation EGFR-TKIs and that therefore a different approach is warranted.
      Finally, we outline dAE management approaches for osimertinib in the context of
      those typically employed with first- and second-generation EGFR-TKIs.
      IMPLICATIONS FOR PRACTICE: Appropriate prevention and management of dermatologic
      adverse events (dAEs) associated with the use of epidermal growth factor receptor
      tyrosine kinase inhibitors (EGFR-TKIs) may help patients to continue therapy and
      lessen any negative impact on their quality of life. EGFR-TKIs are frequently
      associated with acneiform rash, pruritus, xerosis, and paronychia; however, dAEs
      associated with third-generation EGFR-TKIs are lower in frequency and severity.
      Before therapy, health care providers should discuss the potential osimertinib
      associated dAEs and encourage patients to report their dAEs. Patients should also
      be educated on prophylactic measures to minimize the severity of dAEs and the
      importance of adherence to the treatment regimen.

PMID- 29650687
TI  - The Eighth Edition of TNM Staging of Lung Cancer: Reference Chart and Diagrams.
AB  - Lung cancer is the leading cause of cancer-related mortality in the U.S. TNM
      staging of lung cancer is implemented to define the extent of disease and
      consequently assign prognosis and guide treatment. The newest edition of TNM
      staging of lung cancer has been released recently. In this article, we present
      the TNM staging of lung cancer in a concise, yet comprehensive, visual format.

PMID- 29650688
TI  - Outcomes of Elderly Patients with Advanced Soft Tissue Sarcoma Treated with First
      Line Chemotherapy: A Pooled Analysis of 12 EORTC Soft Tissue and Bone Sarcoma
      Group Trials.
AB  - BACKGROUND: Almost half of patients diagnosed with soft tissue sarcoma (STS) are
      older than 65 years; however, the outcomes of elderly patients with metastatic
      disease are not well described. PATIENTS AND METHODS: An elderly cohort of
      patients aged >=65 years was extracted from the European Organization for
      Research and Treatment of Cancer (EORTC) Soft Tissue and Bone Sarcoma Group
      database of patients treated with first-line chemotherapy for advanced STS within
      12 EORTC clinical trials. Endpoints were overall survival (OS), progression-free
      survival (PFS), and response rate (RR). RESULTS: Of 2,810 participants in EORTC
      trials, there were 348 elderly patients (12.4%, median 68 years; interquartile
      range [IQR], 67-70; maximum 84 years) and 2,462 patients aged <65 years (median
      49 years; IQR, 39-57). Most elderly patients had a performance status of 0 (n =
      134; 39%) or 1 (n = 177; 51%). Leiomyosarcoma (n = 130; 37%) was the most common
      histological subtype. Lung metastases were present in 181 patients (52%) and
      liver metastases in 63 patients (18%). Overall, 126 patients (36%) received
      doxorubicin, 114 patients (33%) doxorubicin + ifosfamide, 43 patients (12%)
      epirubicin, 39 patients (11%) trabectedin, and 26 patients (7%) ifosfamide.
      Overall RR was 14.9% (n = 52), median PFS was 3.5 months (95% confidence interval
      [CI], 2.7-4.3), and median OS was 10.8 months (95% CI, 9.43-11.83). In patients
      aged <65 years, overall RR was 20.3% (n = 501), median OS was 12.3 months (95%
      CI, 11.9-12.9), and median PFS was 4.3 months (95% CI, 3.9-4.6). CONCLUSION:
      Elderly patients with metastatic STS treated with first-line chemotherapy were
      largely underrepresented in these EORTC STS trials. Their outcomes were only
      slightly worse than those of younger patients. Novel trials with broader
      eligibility criteria are needed for elderly patients. These trials should
      incorporate geriatric assessments and measurements of age-adjusted health-related
      quality of life. IMPLICATIONS FOR PRACTICE: This analysis demonstrates that
      elderly patients with advanced soft tissue sarcoma are underrepresented in
      clinical trials of first-line chemotherapy by the European Organization for
      Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. Furthermore,
      the elderly participants were generally of excellent performance status, which is
      not representative of an unselected elderly population. These data provide
      rationale for development of novel trials for elderly patients that are not only
      for "elite" patients but include comprehensive geriatric assessments for risk
      stratification. Because chemotherapy for advanced soft tissue sarcomas is largely
      given with palliative intent, incorporation of health-related quality of life
      measures with traditional endpoints will provide a more holistic approach to
      future clinical trials.

PMID- 29650686
TI  - Use of Direct Oral Anticoagulants in Patients with Cancer: Practical
      Considerations for the Management of Patients with Nausea or Vomiting.
AB  - : Direct oral anticoagulants (DOACs) have proven efficacy and safety and are
      approved for use in the prevention and treatment of thromboembolic events in
      patients with venous thromboembolism (VTE) and those with atrial fibrillation
      (AF). There is no clear guidance on the use of DOACs in the significant
      proportion of these patients who have or will develop concomitant cancer. The
      occurrence of nausea and vomiting in these patients, despite implementation of
      guideline-recommended antiemetic strategies, is a particular concern because it
      may affect oral drug intake and consequently outcomes with anticoagulation
      therapy.Here, we review recent data on the incidence and management of cancer
      associated nausea and vomiting and the current evidence and guidance relating to
      the use of DOACs in patients with cancer. On the basis of this evidence, an
      international working group of experts in the fields of cancer-associated
      thrombosis/hemostasis, hematology, and oncology discussed key issues related to
      the use of DOACs in patients with VTE or AF and cancer who are at risk of nausea
      and vomiting and developed some consensus recommendations. We present these
      consensus recommendations, which outline strategies for the use and management of
      anticoagulants, including DOACs, in patients with VTE or AF and cancer for whom
      oral drug intake may pose challenges. Guidance is provided on managing patients
      with gastrointestinal obstruction or nausea and vomiting that is caused by cancer
      treatments or other cancer-related factors.The recommendations outlined in this
      review provide a useful reference for health care professionals and will help to
      improve the management of anticoagulation in patients with VTE or AF and cancer.
      IMPLICATIONS FOR PRACTICE: Direct oral anticoagulants (DOACs) offer several
      advantages over traditional anticoagulants, including ease of administration and
      the lack of need for routine monitoring. However, the management of patients with
      an indication for anticoagulation and concomitant cancer, who are at high risk of
      thromboembolic events, presents several challenges for administering oral
      therapies, particularly with regard to the risk of nausea and vomiting. In the
      absence of robust data from randomized trials and specific guidelines, consensus
      recommendations were developed for healthcare professionals regarding the use of
      DOACs in patients with cancer, with a focus on the management of patients who are
      at risk of nausea and vomiting.

PMID- 29650689
TI  - Role of MRI T2-DRIVE in the assessment of pituitary stalk abnormalities without
      gadolinium in pituitary diseases.
AB  - OBJECTIVE: To investigate the role of T2-DRIVE MRI sequence in the accurate
      measurement of pituitary stalk (PS) size and the identification of PS
      abnormalities in patients with hypothalamic-pituitary disorders without the use
      of gadolinium. DESIGN: This was a retrospective study conducted on 242 patients
      who underwent MRI due to pituitary dysfunction between 2006 and 2015. Among 135
      eligible patients, 102 showed eutopic posterior pituitary (PP) gland and 33
      showed 'ectopic' PP (EPP). METHODS: Two readers independently measured the size
      of PS in patients with eutopic PP at the proximal, midpoint and distal levels on
      pre- and post-contrast T1-weighted as well as T2-DRIVE images; PS visibility was
      assessed on pre-contrast T1 and T2-DRIVE sequences in those with EPP. The length,
      height, width and volume of the anterior pituitary (AP), PP height and length and
      PP area were analyzed. RESULTS: Significant agreement between the two readers was
      obtained for T2-DRIVE PS measurements in patients with 'eutopic' PP; a
      significant difference was demonstrated between the intraclass correlation
      coefficient calculated on the T2-DRIVE and the T1-pre- and post-contrast
      sequences. The percentage of PS identified by T2-DRIVE in EPP patients was 72.7%
      compared to 30.3% of T1 pre-contrast sequences. A significant association was
      found between the visibility of PS on T2-DRIVE and the height of AP. CONCLUSION:
      T2-DRIVE sequence is extremely precise and reliable for the evaluation of PS size
      and the recognition of PS abnormalities; the use of gadolinium-based contrast
      media does not add significant information and may thus be avoided.

PMID- 29650691
TI  - Predictive score for the development or progression of Graves' orbitopathy in
      patients with newly diagnosed Graves' hyperthyroidism.
AB  - OBJECTIVE: To construct a predictive score for the development or progression of
      Graves' orbitopathy (GO) in Graves' hyperthyroidism (GH). DESIGN: Prospective
      observational study in patients with newly diagnosed GH, treated with antithyroid
      drugs (ATD) for 18 months at ten participating centers from EUGOGO in 8 European
      countries. METHODS: 348 patients were included with untreated GH but without
      obvious GO. Mixed effects logistic regression was used to determine the best
      predictors. A predictive score (called PREDIGO) was constructed. RESULTS: GO
      occurred in 15% (mild in 13% and moderate to severe in 2%), predominantly at 6-12
      months after start of ATD. Independent baseline determinants for the development
      of GO were clinical activity score (assigned 5 points if score > 0), TSH-binding
      inhibitory immunoglobulins (2 points if TBII 2-10 U/L, 5 points if TBII > 10
      U/L), duration of hyperthyroid symptoms (1 point if 1-4 months, 3 points if >4
      months) and smoking (2 points if current smoker). Based on the odds ratio of each
      of these four determinants, a quantitative predictive score (called PREDIGO) was
      constructed ranging from 0 to 15 with higher scores denoting higher risk;
      positive and negative predictive values were 0.28 (95% CI 0.20-0.37) and 0.91
      (95% CI 0.87-0.94) respectively. CONCLUSIONS: In patients without GO at
      diagnosis, 15% will develop GO (13% mild, 2% moderate to severe) during
      subsequent treatment with ATD for 18 months. A predictive score called PREDIGO
      composed of four baseline determinants was better in predicting those patients
      who will not develop obvious GO than who will.

PMID- 29650690
TI  - The genetic characteristics of congenital hypothyroidism in China by
      comprehensive screening of 21 candidate genes.
AB  - OBJECTIVE: Congenital hypothyroidism (CH), the most common neonatal metabolic
      disorder, is characterized by impaired neurodevelopment. Although several
      candidate genes have been associated with CH, comprehensive screening of
      causative genes has been limited. DESIGN AND METHODS: One hundred ten patients
      with primary CH were recruited in this study. All exons and exon-intron
      boundaries of 21 candidate genes for CH were analyzed by next-generation
      sequencing. And the inheritance pattern of causative genes was analyzed by the
      study of family pedigrees. RESULTS: Our results showed that 57 patients (51.82%)
      carried biallelic mutations (containing compound heterozygous mutations and
      homozygous mutations) in six genes (DUOX2, DUOXA2, DUOXA1, TG, TPO and TSHR)
      involved in thyroid hormone synthesis. Autosomal recessive inheritance of CH
      caused by mutations in DUOX2, DUOXA2, TG and TPO was confirmed by analysis of 22
      family pedigrees. Notably, eight mutations in four genes (FOXE1, NKX2-1, PAX8 and
      HHEX) that lead to thyroid dysgenesis were identified in eight probands. These
      mutations were heterozygous in all cases and hypothyroidism was not observed in
      parents of these probands. CONCLUSIONS: Most cases of congenital hypothyroidism
      in China were caused by thyroid dyshormonogenesis rather than thyroid dysgenesis.
      This study identified previously reported causative genes for 57/110 Chinese
      patients and revealed DUOX2 was the most frequently mutated gene in these
      patients. Our study expanded the mutation spectrum of CH in Chinese patients,
      which was significantly different from Western countries.

PMID- 29650692
TI  - MicroRNA-Mediated Therapy Modulating Blood-Brain Barrier Disruption Improves
      Vascular Cognitive Impairment.
AB  - OBJECTIVE: There are currently no effective treatments for the prevention of
      dementia associated with vascular cognitive impairment. MicroRNAs regulate gene
      expression at the post-transcriptional level and play key roles in vascular
      disorders. TNFalpha (tumor necrosis factor-alpha) regulates blood-brain barrier
      breakdown through modification of cerebral tight junctions. Here, we sought key
      TNFalpha-responsive microRNAs that might influence blood-brain barrier breakdown
      via cerebral tight junction disruption in vascular cognitive impairment. APPROACH
      AND RESULTS: Using a mouse model of vascular cognitive impairment, chronic
      cerebral hypoperfusion within the white matter was induced with bilateral common
      carotid artery stenosis (BCAS) surgery. TNFalpha gene expression was increased in
      white matter post-BCAS surgery, and TNFalpha stimulation decreased claudin-5, ZO
      1 (tight-junction protein 1), and occludin gene expression in murine brain
      endothelial cells. In silico analysis predicted 8 candidate microRNAs as
      regulators of claudin-5, ZO-1, and occludin gene expression. Of these, only miR
      501-3p was upregulated by TNFalpha in vitro and was upregulated in the white
      matter after BCAS surgery. Further, miR-501-3p directly bound to the 3'
      untranslated region of human ZO-1 and downregulated transendothelial electric
      resistance. In vivo administration of a locked nucleic acid -modified antisense
      oligonucleotide versus miR-501-3p suppressed BCAS-induced reduction of ZO-1 gene
      expression and blood-brain barrier disruption within the white matter and
      significantly ameliorated working memory deficits after BCAS surgery.
      CONCLUSIONS: We here provide the first evidence that the TNFalpha-miR-501-3p-ZO-1
      axis plays an important role in the pathogenesis of cerebral hypoperfusion
      induced working memory deficits and white matter lesions, as a result of blood
      brain barrier breakdown via tight junction disruption. Therapeutic manipulation
      of miR-501-3p holds promise for limiting vascular cognitive impairment
      progression.

PMID- 29650693
TI  - High-Mobility Group Box 1 From Hypoxic Trophoblasts Promotes Endothelial
      Microparticle Production and Thrombophilia in Preeclampsia.
AB  - OBJECTIVE: Thrombophilia is a major complication in preeclampsia, a disease
      associated with placental hypoxia and trophoblast inflammation. Preeclampsia
      women are known to have increased circulating microparticles that are
      procoagulant, but the underlying mechanisms remain unclear. In this study, we
      sought to understand the mechanism connecting placental hypoxia, circulating
      microparticles, and thrombophilia. APPROACH AND RESULTS: We analyzed protein
      markers on plasma microparticles from preeclampsia women and found that the
      increased circulating microparticles were mostly from endothelial cells. In
      proteomic studies, we identified HMGB1 (high-mobility group box 1), a
      proinflammatory protein, as a key factor from hypoxic trophoblasts in stimulating
      microparticle production in human umbilical vein endothelial cells.
      Immunodepletion or inhibition of HMGB1 in the conditioned medium from hypoxic
      human trophoblasts abolished the endothelial microparticle-stimulating activity.
      Conversely, recombinant HMGB1 stimulated microparticle production in cultured
      human umbilical vein endothelial cells. The microparticles from recombinant HMGB1
      stimulated human umbilical vein endothelial cells promoted blood coagulation and
      neutrophil activation in vitro. Injection of recombinant HMGB1 in pregnant mice
      increased plasma endothelial microparticles and promoted blood coagulation. In
      preeclampsia women, elevated placental HMGB1 expression was detected and high
      levels of plasma HMGB1 correlated with increased plasma endothelial
      microparticles. CONCLUSIONS: Our results indicate that placental hypoxia-induced
      HMGB1 expression and release from trophoblasts are important mechanism underlying
      increased circulating endothelial microparticles and thrombophilia in
      preeclampsia.

PMID- 29650694
TI  - Lymphatic Vasculature Requires Estrogen Receptor-alpha Signaling to Protect From
      Lymphedema.
AB  - OBJECTIVE: Estrogens exert beneficial effect on the blood vascular system.
      However, their role on the lymphatic system has been poorly investigated. We
      studied the protective effect of the 17beta estradiol-the most potent endogenous
      estrogen-in lymphedema-a lymphatic dysfunction, which results in a massive fluid
      and fat accumulation in the limb. APPROACH AND RESULTS: Screening of DNA motifs
      able to mobilize ERs (estrogen receptors) and quantitative real-time polymerase
      chain reaction analysis revealed that estradiol promotes transcriptional
      activation of lymphangiogenesis-related gene expression including VEGF (vascular
      endothelial growth factor)-D, VEGFR (VEGF receptor)-3, lyve-1, and HASs
      (hyaluronan synthases). Using an original model of secondary lymphedema, we
      observed a protective effect of estradiol on lymphedema by reducing dermal
      backflow-a representative feature of the pathology. Blocking ERalpha by tamoxifen
      the selective estrogen modulator-led to a remodeling of the lymphatic network
      associated with a strong lymphatic leakage. Moreover, the protection of
      lymphedema by estradiol treatment was abrogated by the endothelial deletion of
      the receptor ERalpha in Tie2-Cre; ERalphalox/lox mice, which exhibit dilated
      lymphatic vessels. This remodeling correlated with a decrease in lymphangiogenic
      gene expression. In vitro, blocking ERalpha by tamoxifen in lymphatic endothelial
      cells decreased cell-cell junctions, inhibited migration and sprouting, and
      resulted in an inhibition of Erk but not of Akt phosphorylation. CONCLUSIONS:
      Estradiol protection from developing lymphedema is mediated by an activation of
      its receptor ERalpha and is antagonized by tamoxifen. These findings reveal a new
      facet of the estrogen influence in the management of the lymphatic system and
      provide more evidence that secondary lymphedema is worsened by hormone therapy.

PMID- 29650695
TI  - Tbx6 controls left-right asymmetry through regulation of Gdf1.
AB  - The Tbx6 transcription factor plays multiple roles during gastrulation, somite
      formation and body axis determination. One of the notable features of the Tbx6
      homozygous mutant phenotype is randomization of left/right axis determination.
      Cilia of the node are morphologically abnormal, leading to the hypothesis that
      disrupted nodal flow is the cause of the laterality defect. However, Tbx6 is
      expressed around but not in the node, leading to uncertainty as to the mechanism
      of this effect. In this study, we have examined the molecular characteristics of
      the node and the genetic cascade determining left/right axis determination. We
      found evidence that a leftward nodal flow is generated in Tbx6 homozygous mutants
      despite the cilia defect, establishing the initial asymmetric gene expression in
      Dand5 around the node, but that the transduction of the signal from the node to
      the left lateral plate mesoderm is disrupted due to lack of expression of the
      Nodal coligand Gdf1 around the node. Gdf1 was shown to be a downstream target of
      Tbx6 and a Gdf1 transgene partially rescues the laterality defect.

PMID- 29650696
TI  - NPY Induces Stress Resilience via Downregulation of Ih in Principal Neurons of
      Rat Basolateral Amygdala.
AB  - Neuropeptide Y (NPY) expression is tightly linked with the development of stress
      resilience in rodents and humans. Local NPY injections targeting the basolateral
      amygdala (BLA) produce long-term behavioral stress resilience in male rats via an
      unknown mechanism. Previously, we showed that activation of NPY Y1 receptors
      hyperpolarizes BLA principal neurons (PNs) through inhibition of the
      hyperpolarization-activated, depolarizing H-current, Ih The present studies
      tested whether NPY treatment induces stress resilience by modulating Ih NPY (10
      pmol) was delivered daily for 5 d bilaterally into the BLA to induce resilience;
      thereafter, the electrophysiological properties of PNs and the expression of Ih
      in the BLA were characterized. As reported previously, increases in social
      interaction (SI) times persisted weeks after completion of NPY administration. In
      vitro intracellular recordings showed that repeated intra-BLA NPY injections
      resulted in hyperpolarization of BLA PNs at 2 weeks (2W) and 4 weeks (4W) after
      NPY treatment. At 2W, spontaneous IPSC frequencies were increased, whereas at 4W,
      resting Ih was markedly reduced and accompanied by decreased levels of HCN1 mRNA
      and protein expression in BLA. Knock-down of HCN1 channels in the BLA with
      targeted delivery of lentivirus containing HCN1-shRNA increased SI beginning 2W
      after injection and induced stress resilience. NPY treatment induced sequential,
      complementary changes in the inputs to BLA PNs and their postsynaptic properties
      that reduce excitability, a mechanism that contributes to less anxious behavior.
      Furthermore, HCN1 knock-down mimicked the increases in SI and stress resilience
      observed with NPY, indicating the importance of Ih in stress-related
      behavior.SIGNIFICANCE STATEMENT Resilience improves mental health outcomes in
      response to adverse situations. Neuropeptide Y (NPY) is associated with decreased
      stress responses and the expression of resilience in rodents and humans. Single
      or repeated injections of NPY into the basolateral amygdala (BLA) buffer negative
      behavioral effects of stress and induce resilience in rats, respectively. Here,
      we demonstrate that repeated administration of NPY into the BLA unfolds several
      cellular mechanisms that decrease the activity of pyramidal output neurons. One
      key mechanism is a reduction in levels of the excitatory ion channel HCN1.
      Moreover, shRNA knock-down of HCN1 expression in BLA recapitulates some of the
      actions of NPY and causes potent resilience to stress, indicating that this
      channel may be a possible target for therapy.

PMID- 29650697
TI  - Cell-Type-Specific Contributions of Medial Prefrontal Neurons to Flexible
      Behaviors.
AB  - Behavioral flexibility and impulse control are necessary for successful execution
      of adaptive behavior. They are impaired in patients with damage to the prefrontal
      cortex (PFC) and in some clinically important conditions, such as obsessive
      compulsive disorder. Although the medial prefrontal cortex (mPFC) has been
      investigated as a critical structure for behavioral flexibility and impulse
      control, the contribution of the underlying pyramidal neuron cell types in the
      mPFC remained to be understood. Here we show that interneuron-mediated local
      inactivation of pyramidal neurons in the mPFC of male and female mice induces
      both premature responses and choice bias, and establish that these impulsive and
      compulsive responses are modulated independently. Cell-type-specific
      photoinhibition of pyramidal deep layer corticostriatal or corticothalamic
      neurons reduces behavioral flexibility without inducing premature responses.
      Together, our data confirm the role of corticostriatal neurons in behavioral
      flexibility and demonstrate that flexible behaviors are also modulated by direct
      projections from deep layer corticothalamic neurons in the mPFC to midline
      thalamic nuclei.SIGNIFICANCE STATEMENT Behavioral flexibility and impulse control
      are indispensable for animals to adapt to changes in the environment and often
      affected in patients with PFC damage and obsessive-compulsive disorder. We used a
      probabilistic reversal task to dissect the underlying neural circuitry in the
      mPFC. Through characterization of the three major pyramidal cell types in the
      mPFC with optogenetic silencing, we demonstrated that corticostriatal and
      corticothalamic but not corticocortical pyramidal neurons are temporally
      recruited for behavioral flexibility. Together, our findings confirm the role of
      corticostriatal projections in cognitive flexibility and identify corticothalamic
      neurons as equally important for behavioral flexibility.

PMID- 29650698
TI  - Credit Assignment in a Motor Decision Making Task Is Influenced by Agency and Not
      Sensory Prediction Errors.
AB  - Failures to obtain reward can occur from errors in action selection or action
      execution. Recently, we observed marked differences in choice behavior when the
      failure to obtain a reward was attributed to errors in action execution compared
      with errors in action selection (McDougle et al., 2016). Specifically,
      participants appeared to solve this credit assignment problem by discounting
      outcomes in which the absence of reward was attributed to errors in action
      execution. Building on recent evidence indicating relatively direct communication
      between the cerebellum and basal ganglia, we hypothesized that cerebellar
      dependent sensory prediction errors (SPEs), a signal indicating execution
      failure, could attenuate value updating within a basal ganglia-dependent
      reinforcement learning system. Here we compared the SPE hypothesis to an
      alternative, "top-down" hypothesis in which changes in choice behavior reflect
      participants' sense of agency. In two experiments with male and female human
      participants, we manipulated the strength of SPEs, along with the participants'
      sense of agency in the second experiment. The results showed that, whereas the
      strength of SPE had no effect on choice behavior, participants were much more
      likely to discount the absence of rewards under conditions in which they believed
      the reward outcome depended on their ability to produce accurate movements. These
      results provide strong evidence that SPEs do not directly influence reinforcement
      learning. Instead, a participant's sense of agency appears to play a significant
      role in modulating choice behavior when unexpected outcomes can arise from errors
      in action execution.SIGNIFICANCE STATEMENT When learning from the outcome of
      actions, the brain faces a credit assignment problem: Failures of reward can be
      attributed to poor choice selection or poor action execution. Here, we test a
      specific hypothesis that execution errors are implicitly signaled by cerebellar
      based sensory prediction errors. We evaluate this hypothesis and compare it with
      a more "top-down" hypothesis in which the modulation of choice behavior from
      execution errors reflects participants' sense of agency. We find that sensory
      prediction errors have no significant effect on reinforcement learning. Instead,
      instructions influencing participants' belief of causal outcomes appear to be the
      main factor influencing their choice behavior.

PMID- 29650699
TI  - Update of an occupational asthma-specific job exposure matrix to assess exposure
      to 30 specific agents.
AB  - OBJECTIVES: We aimed to update an asthmagen job exposure matrix (JEM) developed
      in the late 1990s. Main reasons were: the number of suspected and recognised
      asthmagens has since tripled; understanding of the aetiological role of irritants
      in asthma and methodological insights in application of JEMs have emerged in the
      period. METHODS: For each agent of the new occupational asthma-specific JEM
      (OAsJEM), a working group of three experts out of eight evaluated exposure for
      each International Standard Classification of Occupations, 1988 (ISCO-88) job
      code into three categories: 'high' (high probability of exposure and moderate-to
      high intensity), 'medium' (low-to-moderate probability or low intensity) and
      'unexposed'. Within a working group, experts evaluated exposures independently
      from each other. If expert assessments were inconsistent the final decision was
      taken by consensus. Specificity was favoured over sensitivity, that is, jobs were
      classified with high exposure only if the probability of exposure was high and
      the intensity moderate-to-high. In the final review, all experts checked assigned
      exposures and proposed/improved recommendations for expert re-evaluation after
      default application of the JEM. RESULTS: The OAsJEM covers exposures to 30
      sensitisers/irritants, including 12 newly recognised, classified into seven broad
      groups. Initial agreement between the three experts was mostly fair to moderate
      (kappa values 0.2-0.5). Out of 506 ISCO-88 codes, the majority was classified as
      unexposed (from 82.6% (organic solvents) to 99.8% (persulfates)) and a minority
      as 'high-exposed' (0.2% (persulfates) to 2.6% (organic solvents)). CONCLUSIONS:
      The OAsJEM developed to improve occupational exposure assessment may improve
      evaluations of associations with asthma in epidemiological studies and contribute
      to assessment of the burden of work-related asthma.

PMID- 29650700
TI  - Building one molecule from a reservoir of two atoms.
AB  - Chemical reactions typically proceed via stochastic encounters between reactants.
      Going beyond this paradigm, we combined exactly two atoms in a single, controlled
      reaction. The experimental apparatus traps two individual laser-cooled atoms [one
      sodium (Na) and one cesium (Cs)] in separate optical tweezers and then merges
      them into one optical dipole trap. Subsequently, photoassociation forms an
      excited-state NaCs molecule. The discovery of previously unseen resonances near
      the molecular dissociation threshold and measurement of collision rates are
      enabled by the tightly trapped ultracold sample of atoms. As laser-cooling and
      trapping capabilities are extended to more elements, the technique will enable
      the study of more diverse, and eventually more complex, molecules in an isolated
      environment, as well as synthesis of designer molecules for qubits.

PMID- 29650701
TI  - Elastic strain engineering for ultralow mechanical dissipation.
AB  - Extreme stresses can be produced in nanoscale structures; this feature has been
      used to realize enhanced materials properties, such as the high mobility of
      silicon in modern transistors. We show how nanoscale stress can be used to
      realize exceptionally low mechanical dissipation when combined with "soft
      clamping"-a form of phononic engineering. Specifically, using a nonuniform
      phononic crystal pattern, we colocalize the strain and flexural motion of a free
      standing silicon nitride nanobeam. Ringdown measurements at room temperature
      reveal string-like vibrational modes with quality (Q) factors as high as 800
      million and Q * frequency exceeding 1015 hertz. These results illustrate a
      promising route for engineering ultracoherent nanomechanical devices.

PMID- 29650702
TI  - RNA buffers the phase separation behavior of prion-like RNA binding proteins.
AB  - Prion-like RNA binding proteins (RBPs) such as TDP43 and FUS are largely soluble
      in the nucleus but form solid pathological aggregates when mislocalized to the
      cytoplasm. What keeps these proteins soluble in the nucleus and promotes
      aggregation in the cytoplasm is still unknown. We report here that RNA critically
      regulates the phase behavior of prion-like RBPs. Low RNA/protein ratios promote
      phase separation into liquid droplets, whereas high ratios prevent droplet
      formation in vitro. Reduction of nuclear RNA levels or genetic ablation of RNA
      binding causes excessive phase separation and the formation of cytotoxic solid
      like assemblies in cells. We propose that the nucleus is a buffered system in
      which high RNA concentrations keep RBPs soluble. Changes in RNA levels or RNA
      binding abilities of RBPs cause aberrant phase transitions.

PMID- 29650703
TI  - mRNA structure determines specificity of a polyQ-driven phase separation.
AB  - RNA promotes liquid-liquid phase separation (LLPS) to build membraneless
      compartments in cells. How distinct molecular compositions are established and
      maintained in these liquid compartments is unknown. Here, we report that
      secondary structure allows messenger RNAs (mRNAs) to self-associate and
      determines whether an mRNA is recruited to or excluded from liquid compartments.
      The polyQ-protein Whi3 induces conformational changes in RNA structure and
      generates distinct molecular fluctuations depending on the RNA sequence. These
      data support a model in which structure-based, RNA-RNA interactions promote
      assembly of distinct droplets and protein-driven, conformational dynamics of the
      RNA maintain this identity. Thus, the shape of RNA can promote the formation and
      coexistence of the diverse array of RNA-rich liquid compartments found in a
      single cell.

PMID- 29650704
TI  - High-resolution cryo-EM analysis of the yeast ATP synthase in a lipid membrane.
AB  - Mitochondrial adenosine triphosphate (ATP) synthase comprises a membrane embedded
      Fo motor that rotates to drive ATP synthesis in the F1 subunit. We used single
      particle cryo-electron microscopy (cryo-EM) to obtain structures of the full
      complex in a lipid bilayer in the absence or presence of the inhibitor oligomycin
      at 3.6- and 3.8-angstrom resolution, respectively. To limit conformational
      heterogeneity, we locked the rotor in a single conformation by fusing the F6
      subunit of the stator with the delta subunit of the rotor. Assembly of the enzyme
      with the F6-delta fusion caused a twisting of the rotor and a 9 degrees  rotation
      of the Fo c10-ring in the direction of ATP synthesis, relative to the structure
      of isolated Fo Our cryo-EM structures show how F1 and Fo are coupled, give
      insight into the proton translocation pathway, and show how oligomycin blocks ATP
      synthesis.

PMID- 29650705
TI  - Outcomes of Peripheral Vascular Interventions in Select Patients With Lower
      Extremity Acute Limb Ischemia.
AB  - BACKGROUND: Contemporary data on patients presenting with acute limb ischemia
      (ALI), who are selected for treatment with endovascular peripheral vascular
      interventions (PVI), are limited. Our study examined outcomes following
      endovascular PVI in patients with ALI by comparing with patients treated for
      chronic critical limb ischemia using a regional quality improvement registry.
      METHODS AND RESULTS: Of the 11 035 patients in the Vascular Study Group of New
      England PVI database (2010-2014), we identified 365 patients treated for lower
      extremity ALI who were 5:1 frequency matched (by procedure year and arterial
      segments treated) to 1808 patients treated for critical limb ischemia. ALI
      patients treated with PVI had high burden of atherosclerotic risk factors and
      were more likely to have had prior ipsilateral revascularizations. ALI patients
      were less likely to be treated with self-expanding stents and more likely to
      undergo thrombolysis than patients with critical limb ischemia. In multivariable
      analysis, ALI was associated with higher technical failure (odds ratio 1.7, 95%
      confidence interval, 1.1%-2.5%), increased rate of distal embolization (odds
      ratio 2.7, 95% confidence interval, 1.5%-4.9%), longer length of stay (means
      ratio 1.6, 95% confidence interval, 1.4%-1.8%), and higher in-hospital mortality
      (odds ratio 2.8, 95% confidence interval, 1.3%-5.9%). ALI was not associated with
      risk of major amputation or mortality at 1 year. CONCLUSIONS: In a multicenter
      cohort of patients treated with PVI, we found that ALI patients selected for
      treatment with endovascular techniques experienced greater short-term adverse
      events but similar long-term outcomes as their critical limb ischemia
      counterparts. Further studies are needed to refine the selection of ALI patients
      who are best served by PVI.

PMID- 29650706
TI  - Pro-Inflammatory Biomarkers in Stable Versus Acutely Decompensated Heart Failure
      With Preserved Ejection Fraction.
AB  - BACKGROUND: Underlying inflammation has been increasingly recognized in heart
      failure with a preserved ejection fraction (HFpEF). In this study we tested the
      hypothesis that pro-inflammatory biomarkers are elevated in patients with acutely
      decompensated HFpEF (AD-HFpEF) compared with patients with stable HFpEF (S
      HFpEF). METHODS AND RESULTS: Using a post hoc analysis the serum biomarkers tumor
      necrosis factor-alpha, high-sensitivity C-reactive protein interleukin 6 and
      pentraxin 3 (PTX3) and clinical, demographic, echocardiographic-Doppler and
      clinical outcomes data were analyzed in HFpEF patients enrolled in NHLBI Heart
      Failure Research Network clinical trials which enrolled patients with either AD
      HFpEF or S-HFpEF. Compared to S-HFpEF, AD-HFpEF patients had higher levels of
      PTX3 (3.08 ng/mL versus 1.27 ng/mL, P<0.0001), interleukin-6 (4.14 pg/mL versus
      1.71 pg/mL, P<0.0001), tumor necrosis factor-alpha (11.54 pg/mL versus 8.62
      pg/mL, P=0.0015), and high-sensitivity C-reactive protein (11.90 mg/dL versus
      3.42 mg/dL, P<0.0001). Moreover, high-sensitivity C-reactive protein, interleukin
      6 and PTX3 levels were significantly higher in AD-HFpEF compared with S-HFpEF
      patients admitted for decompensated HF within the previous year. PTX3 was
      positively correlated with left atrial volume index (r=0.41, P=0.0017) and left
      ventricular mass (r=0.26, P=0.0415), while tumor necrosis factor-alpha was
      inversely correlated with E/A ratio (r=-0.31, P=0.0395). CONCLUSIONS: Levels of
      pro-inflammatory biomarkers are strikingly higher in AD-HFpEF compared with S
      HFpEF patients. PTX3 and tumor necrosis factor-alpha are correlated with
      echocardiographic-Doppler evidence of diastolic dysfunction. Taken together these
      data support the concept that a heightened pro-inflammatory state has a
      pathophysiologic role in the development of AD-HFpEF.

PMID- 29650707
TI  - Errors in Electronic Health Record-Based Data Query of Statin Prescriptions in
      Patients With Coronary Artery Disease in a Large, Academic, Multispecialty Clinic
      Practice.
AB  - BACKGROUND: With the recent implementation of the Medicare Quality Payment
      Program, providers face increasing accountability for delivering high-quality
      care. Such pay-for-performance programs aim to leverage systematic data captured
      by electronic health record (EHR) systems to measure performance; however, the
      fidelity of EHR query for assessing performance has not been validated compared
      with manual chart review. We sought to determine whether our institution's
      methodology of EHR query could accurately identify cases in which providers
      failed to prescribe statins for eligible patients with coronary artery disease.
      METHODS AND RESULTS: A total of 9459 patients with coronary artery disease were
      seen at least twice at the Emory Clinic between July 2014 and June 2015, of whom
      1338 (14.1%, 95% confidence interval 13.5-14.9%) had no statin prescription or
      exemption per EHR query. A total of 120 patient cases were randomly selected and
      reviewed by 2 physicians for further adjudication. Of the 120 cases initially
      classified as statin prescription failures, only 21 (17.5%; 95% confidence
      interval, 11.7-25.3%) represented true failure following physician review.
      CONCLUSIONS: Sole reliance on EHR data query to measure quality metrics may lead
      to significant errors in assessing provider performance. Institutions should be
      cognizant of these potential sources of error, provide support to medical
      providers, and form collaborative data management teams to promote and improve
      meaningful use of EHRs. We propose actionable steps to improve the accuracy of
      EHR data query that require hypothesis testing and prospective validation in
      future studies.

PMID- 29650708
TI  - Outcomes in Asymptomatic Severe Aortic Stenosis With Preserved Ejection Fraction
      Undergoing Rest and Treadmill Stress Echocardiography.
AB  - BACKGROUND: In asymptomatic patients with severe aortic stenosis and preserved
      left ventricular ejection fraction, we sought to assess the incremental
      prognostic value of resting valvuloarterial impedence (Zva) and left ventricular
      global longitudinal strain (LV-GLS) to treadmill stress echocardiography. METHODS
      AND RESULTS: We studied 504 such patients (66+/-12 years, 78% men, 32% with
      coronary artery disease who underwent treadmill stress echocardiography between
      2001 and 2012. Clinical and exercise variables (% of age-sex predicted metabolic
      equivalents [%AGP-METs]) were recorded. Resting Zva ([systolic arterial
      pressure+mean aortic valve gradient]/[LV-stroke volume index]) and LV-GLS
      (measured offline using Velocity Vector Imaging, Siemens) were obtained from the
      baseline resting echocardiogram. Death was the primary outcome. There were no
      major adverse cardiac events during treadmill stress echocardiography. Indexed
      aortic valve area, Zva, and LV-GLS were 0.46+/-0.1 cm2/m2, 4.5+/-0.9 mm Hg/mL per
      m2 and -16+/-4%, respectively; only 50% achieved >100% AGP-METs. Sixty-four
      percent underwent aortic valve replacement. Death occurred in 164 (33%) patients
      over 8.9+/-3.6 years (2 within 30 days of aortic valve replacement). On
      multivariable Cox survival analysis, higher Society of Thoracic Surgeons score
      (hazard ratio or HR 1.06), lower % AGP-METS (HR 1.16), higher Zva (HR 1.25) and
      lower LV-GLS (HR 1.12) were associated with higher longer-term mortality, while
      aortic valve replacement (HR 0.45) was associated with improved survival (all
      P<0.01). Sequential addition of ZVa and LV-GLS to clinical model (Society of
      Thoracic Surgeons score and %AGP-METs) increased the c-statistic from 0.65 to
      0.69 and 0.75, respectively, both P<0.001); findings were similar in the subgroup
      of patients who underwent aortic valve replacement. CONCLUSIONS: In asymptomatic
      patients with severe aortic stenosis undergoing treadmill stress
      echocardiography, LV-GLS and ZVa offer incremental prognostic value.

PMID- 29650709
TI  - Machine Learning Methods Improve Prognostication, Identify Clinically Distinct
      Phenotypes, and Detect Heterogeneity in Response to Therapy in a Large Cohort of
      Heart Failure Patients.
AB  - BACKGROUND: Whereas heart failure (HF) is a complex clinical syndrome,
      conventional approaches to its management have treated it as a singular disease,
      leading to inadequate patient care and inefficient clinical trials. We
      hypothesized that applying advanced analytics to a large cohort of HF patients
      would improve prognostication of outcomes, identify distinct patient phenotypes,
      and detect heterogeneity in treatment response. METHODS AND RESULTS: The Swedish
      Heart Failure Registry is a nationwide registry collecting detailed demographic,
      clinical, laboratory, and medication data and linked to databases with outcome
      information. We applied random forest modeling to identify predictors of 1-year
      survival. Cluster analysis was performed and validated using serial
      bootstrapping. Association between clusters and survival was assessed with Cox
      proportional hazards modeling and interaction testing was performed to assess for
      heterogeneity in response to HF pharmacotherapy across propensity-matched
      clusters. Our study included 44 886 HF patients enrolled in the Swedish Heart
      Failure Registry between 2000 and 2012. Random forest modeling demonstrated
      excellent calibration and discrimination for survival (C-statistic=0.83) whereas
      left ventricular ejection fraction did not (C-statistic=0.52): there were no
      meaningful differences per strata of left ventricular ejection fraction (1-year
      survival: 80%, 81%, 83%, and 84%). Cluster analysis using the 8 highest
      predictive variables identified 4 clinically relevant subgroups of HF with marked
      differences in 1-year survival. There were significant interactions between
      propensity-matched clusters (across age, sex, and left ventricular ejection
      fraction and the following medications: diuretics, angiotensin-converting enzyme
      inhibitors, beta-blockers, and nitrates, P<0.001, all). CONCLUSIONS: Machine
      learning algorithms accurately predicted outcomes in a large data set of HF
      patients. Cluster analysis identified 4 distinct phenotypes that differed
      significantly in outcomes and in response to therapeutics. Use of these novel
      analytic approaches has the potential to enhance effectiveness of current
      therapies and transform future HF clinical trials.

PMID- 29650710
TI  - Plasma Concentrations and Dietary Intakes of Choline and Betaine in Association
      With Atrial Fibrillation Risk: Results From 3 Prospective Cohorts With Different
      Health Profiles.
AB  - BACKGROUND: Although choline metabolism has been associated with atherosclerotic
      heart disease, less research attention has been paid to the associations of
      choline and its oxidative metabolite betaine with cardiac arrhythmias. METHODS
      AND RESULTS: We evaluated associations of plasma concentrations and dietary
      intakes of choline and betaine with long-term atrial fibrillation (AF) risk in a
      community-based cohort, HUSK ([the Hordaland Health Study] n=6949), and validated
      the findings in 2 patient cohorts: the Western Norway Coronary Angiography Cohort
      (n=4164) and the NORVIT (Norwegian B-Vitamin) Trial (n=3733). Information on AF
      was obtained from the CVDNOR (Cardiovascular Disease in Norway) project. In HUSK,
      WECAC (Western Norway Coronary Angiography Cohort), and NORVIT, 552, 411, and 663
      AF cases were identified during a median follow-up time of 10.9, 7.3, and, 8.7
      years, respectively. Plasma concentrations of choline and betaine were
      significantly positively associated with later AF risk after multivariable
      adjustments in HUSK. Such associations were independently replicated in the 2
      external prospective patient cohorts. The pooled hazard ratio was 1.13 (95%
      confidence interval 1.08-1.19, P<0.001) and 1.16 (95% confidence interval 1.10
      1.22, P<0.001) per SD increment for log-transformed choline and betaine,
      respectively. Moreover, dietary intake of choline was marginally associated with
      AF risk (pooled hazard ratio 1.29, 95% confidence interval 1.01-1.66, fifth
      versus first quintile), whereas no significant association was observed between
      dietary betaine and AF risk. CONCLUSIONS: Our findings indicate that plasma
      concentrations as well as dietary intake of choline, but not betaine, are
      associated with subsequent risk of AF, suggesting a potential role of choline
      metabolism in the pathogenesis of AF. CLINICAL TRIAL REGISTRATION: URL:
      https://www.clinicaltrials.gov.Unique identifier: NCT00671346.

PMID- 29650711
TI  - American Heart Association's Life Simple 7 and Risk of Atrial Fibrillation in a
      Population Without Known Cardiovascular Disease: The ARIC (Atherosclerosis Risk
      in Communities) Study.
AB  - BACKGROUND: The American Heart Association has defined metrics of ideal
      cardiovascular health known as Life's Simple 7 (LS7) to prevent cardiovascular
      disease. We examined the association between LS7 and incident atrial fibrillation
      (AF) in a biracial cohort of middle- and older-aged adults without known
      cardiovascular disease. METHODS AND RESULTS: This analysis included 13 182 ARIC
      (Atherosclerosis Risk in Communities) study participants (mean baseline age=54+/
      5.7 years; 56% women; 25% black) free of AF and cardiovascular disease. An
      overall LS7 score was calculated as the sum of the LS7 component scores and
      classified as inadequate (0-4), average (5-9), or optimal (10-14) cardiovascular
      health. The primary outcome was incident AF, identified primarily by ECG and
      hospital discharge coding of AF through December 31, 2014. A total of 2266 (17%)
      incident AF cases were detected over a median follow-up of 25.1 years. Compared
      with the inadequate category (n=1057), participants in the average (n=8629) and
      optimal (n=3496) categories each had a lower risk of developing AF in a
      multivariable Cox proportional hazards model (hazard ratio 0.59, 95% confidence
      interval 0.51, 0.67 for average; and hazard ratio 0.38, 95% confidence interval
      0.32, 0.44 for optimal). In a similar model, a 1-point-higher LS7 score was
      associated with a 12% lower risk of incident AF (hazard ratio 0.88, 95%
      confidence interval 0.86, 0.89). CONCLUSIONS: A higher LS7 score is strongly
      associated with a lower risk of AF in individuals without baseline cardiovascular
      disease. Determining whether interventions that improve the population's
      cardiovascular health also reduce AF incidence is needed.

PMID- 29650712
TI  - Outcome Prediction in Acute Stroke Patients by Continuous Glucose Monitoring.
AB  - BACKGROUND: The purpose of this study was to examine the relationships between
      glucose parameters obtained by continuous glucose monitoring and clinical
      outcomes in acute stroke patients. METHODS AND RESULTS: Consecutive patients with
      acute ischemic stroke or intracerebral hemorrhage within 24 hours after onset
      were included. A continuous glucose monitoring device (iPro2) was attached for
      the initial 72 hours after emergent admission. Eight glucose parameters were
      obtained from continuous glucose monitoring: maximum, minimum, mean, and SD of
      blood glucose levels, as well as area under the curve more than 8 mmol/L of blood
      glucose, distribution time more than 8 mmol/L of blood glucose, coefficient of
      variation (%CV), and presence of time less than 4 mmol/L over 72 hours. The
      primary outcome measure was death or dependency at 3 months (modified Rankin
      Scale score >=3). One hundred patients with acute ischemic stroke (n=58) or
      intracerebral hemorrhage (n=42) were included. Blood glucose levels varied
      between 5.2+/-1.4 and 11.4+/-3.2 mmol/L over 72 hours, with area under the curve
      more than 8 mmol/L of blood glucose of 0.7+/-1.4 min*mmol/L, distribution time
      more than 8 mmol/L of blood glucose of 31.7+/-32.7%, coefficient of variation of
      15.5+/-5.4%, and presence of hypoglycemia in 20% of overall patients. Mean
      glucose level (adjusted odds ratio, 1.60, 95% confidence interval, 1.12-2.28/1
      mmol/L), area under the curve more than 8 mmol/L of blood glucose (2.13, 1.12
      4.02/1 min*mmol/L), and distribution time more than 8 mmol/L of blood glucose
      (1.25, 1.05-1.50/10%) were related to death or dependency for overall patients,
      as well as for acute ischemic stroke patients (2.05, 1.15-3.65; 2.38, 1.04-5.44;
      1.85, 1.10-3.10, respectively). CONCLUSIONS: High mean glucose levels,
      distribution time more than 8 mmol/L of blood glucose, and areas under the curve
      more than 8 mmol/L of blood glucose during the initial 72 hours of acute stroke
      were associated with death or dependency at 3 months.

PMID- 29650713
TI  - Is Achieving the American Heart Association's Life Simple 7 Goals Sufficient to
      Reduce the Burden of Atrial Fibrillation? No Simple Answers.

PMID- 29650715
TI  - Watchdog bans "misleading" ads for online GP consultation service Push Doctor.

PMID- 29650714
TI  - Awareness of Racial Disparities in Kidney Transplantation among Health Care
      Providers in Dialysis Facilities.
AB  - BACKGROUND AND OBJECTIVES: Despite the important role that health care providers
      at dialysis facilities have in reducing racial disparities in access to kidney
      transplantation in the United States, little is known about provider awareness of
      these disparities. We aimed to evaluate health care providers' awareness of
      racial disparities in kidney transplant waitlisting and identify factors
      associated with awareness. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We
      conducted a cross-sectional analysis of a survey of providers from low
      waitlisting dialysis facilities (n=655) across all 18 ESRD networks administered
      in 2016 in the United States merged with 2014 US Renal Data System and 2014 US
      Census data. Awareness of national racial disparity in waitlisting was defined as
      responding "yes" to the question: "Nationally, do you think that African
      Americans currently have lower waitlisting rates than white patients on average?"
      The secondary outcome was providers' perceptions of racial difference in
      waitlisting at their own facilities. RESULTS: Among 655 providers surveyed, 19%
      were aware of the national racial disparity in waitlisting: 50% (57 of 113) of
      medical directors, 11% (35 of 327) of nurse managers, and 16% (35 of 215) of
      other providers. In analyses adjusted for provider and facility characteristics,
      nurse managers (versus medical directors; odds ratio, 7.33; 95% confidence
      interval, 3.35 to 16.0) and white providers (versus black providers; odds ratio,
      2.64; 95% confidence interval, 1.39 to 5.02) were more likely to be unaware of a
      national racial disparity in waitlisting. Facilities in the South (versus the
      Northeast; odds ratio, 3.05; 95% confidence interval, 1.04 to 8.94) and
      facilities with a low percentage of blacks (versus a high percentage of blacks;
      odds ratio, 1.86; 95% confidence interval, 1.02 to 3.39) were more likely to be
      unaware. One quarter of facilities had >5% racial difference in waitlisting
      within their own facilities, but only 5% were aware of the disparity.
      CONCLUSIONS: Among a limited sample of dialysis facilities with low waitlisting,
      provider awareness of racial disparities in kidney transplant waitlisting was
      low, particularly among staff who may have more routine contact with patients.

PMID- 29650716
TI  - Cardiovascular Genetic Risk Testing for Targeting Statin Therapy in the Primary
      Prevention of Atherosclerotic Cardiovascular Disease: A Cost-Effectiveness
      Analysis.
AB  - BACKGROUND: It is unclear whether testing for novel risk factors, such as a
      cardiovascular genetic risk score (cGRS), improves clinical decision making or
      health outcomes when used for targeting statin initiation in the primary
      prevention of atherosclerotic cardiovascular disease (ASCVD). Our objective was
      to estimate the cost-effectiveness of cGRS testing to inform clinical decision
      making about statin initiation in individuals with low-to-intermediate (2.5%
      7.5%) 10-year predicted risk of ASCVD. METHODS AND RESULTS: We evaluated the cost
      effectiveness of testing for a 27-single-nucleotide polymorphism cGRS comparing 4
      test/treat strategies: treat all, treat none, test/treat if cGRS is high, and
      test/treat if cGRS is intermediate or high. We tested a set of clinical scenarios
      of men and women, aged 45 to 65 years, with 10-year ASCVD risks between 2.5% and
      7.5%. Our primary outcome measure was cost per quality-adjusted life-year gained.
      Under base case assumptions for statin disutility and cost, the preferred
      strategy is to treat all patients with ASCVD risk >2.5% without cGRS testing. For
      certain clinical scenarios, such as a 57-year-old man with a 10-year ASCVD risk
      of 7.5%, cGRS testing can be cost-effective under a limited set of assumptions;
      for example, when statins cost $15 per month and statin disutility is 0.013 (ie,
      willing to trade 3 months of life in perfect health to avoid 20 years of statin
      therapy), the preferred strategy (using a willingness-to-pay threshold of $50 000
      per quality-adjusted life-year gained) is to test and treat if cGRS is
      intermediate or high. Overall, the results were not sensitive to assumptions
      about statin efficacy and harms. CONCLUSIONS: Testing for a 27-single-nucleotide
      polymorphism cGRS is generally not a cost-effective approach for targeting statin
      therapy in the primary prevention of ASCVD for low- to intermediate-risk
      patients.

PMID- 29650717
TI  - National Trends of Hospital Performance in Acute Myocardial Infarction Care:
      Department of Veterans Affairs, 2011-2014.

PMID- 29650718
TI  - Statins and the Classic Decision Analysis: Treat, Test, or Neither?

PMID- 29650719
TI  - Science in Social Media: Debating the Effects of Readmission Penalties.

PMID- 29650720
TI  - Academic Cardiology and Social Media: Navigating the Wisdom and Madness of the
      Crowd.

PMID- 29650721
TI  - LECT2 promotes inflammation and insulin resistance in adipocytes via P38
      pathways.
AB  - Leukocyte cell-derived chemotaxin 2 (LECT2) is a recently identified novel
      hepatokine that causes insulin resistance in skeletal muscle by activating c-Jun
      N-terminal kinase (JNK), thereby driving atherosclerotic inflammation. However,
      the role of LECT2 in inflammation and insulin resistance in adipocytes has not
      been investigated. In this study, we report that LECT2 treatment of
      differentiated 3T3-L1 cells stimulates P38 phosphorylation in a dose-dependent
      manner. LECT2 also enhanced inflammation markers such as IkappaB phosphorylation,
      nuclear factor kappa beta (NF-kappaB) phosphorylation and IL-6 expression.
      Moreover, LECT2 treatment impaired insulin signaling in differentiated 3T3-L1
      cells, as evidenced by the decreased levels of insulin receptor substrate (IRS-1)
      and Akt phosphorylation and reduced insulin-stimulated glucose uptake.
      Furthermore, LECT2 augmented lipid accumulation during 3T3-L1 cell
      differentiation by activating SREBP1c-mediated signaling. All these effects were
      significantly abrogated by siRNA-mediated silencing of P38, CD209 expression or a
      JNK inhibitor. Our findings suggest that LECT2 stimulates inflammation and
      insulin resistance in adipocytes via activation of a CD209/P38-dependent pathway.
      Thus, these results suggest effective therapeutic targets for treating
      inflammation-mediated insulin resistance.

PMID- 29650722
TI  - Challenge of communicating uncertainty in systematic reviews when applying GRADE
      ratings.

PMID- 29650723
TI  - Rivaroxaban plus aspirin, compared with aspirin alone, reduced cardiovascular
      events in patients with stable peripheral or carotid artery disease, but
      increased the risk of major bleeding.

PMID- 29650724
TI  - When authors lie, readers cry and editors sigh.

PMID- 29650725
TI  - The effect of publication bias magnitude and direction on the certainty in
      evidence.
AB  - Publication bias occurs when studies with statistically significant results have
      increased likelihood of being published. Publication bias is commonly associated
      with inflated treatment effect which lowers the certainty of decision makers
      about the evidence. In this guide we propose that systematic reviewers and
      decision makers consider the direction and magnitude of publication bias, as
      opposed to just the binary determination of the presence of this bias, before
      lowering their certainty in the evidence. Direction of bias may not always
      exaggerate the treatment effect. The presence of bias with a trivial magnitude
      may not affect the decision at hand. Various statistical approaches are available
      to determine the direction and magnitude of publication bias.

PMID- 29650726
TI  - Reduction of healthcare costs through a transitions-of-care program.
AB  - PURPOSE: Results of an evaluation of the impact of a pharmacy-based transitional
      care program on healthcare costs in a population of high-risk patients are
      reported. METHODS: A nonrandomized, observational cohort study was conducted to
      compare cost outcomes in a group of patients discharged from a single hospital
      who were referred to an ambulatory care pharmacy-based transitions-of-care (TOC)
      program and a control group of patients discharged from neighboring hospitals who
      received usual care; all patients were members of the same managed Medicaid plan.
      The intervention and control groups were matched by number of hospitalizations
      during the 180 days preceding the index admission and by index admission length
      of stay. In the intervention group, all matched patients referred for TOC
      services (including those who did not qualify for services, could not be
      contacted, or declined services) were included in an intent-to-treat analysis.
      Thirty- and 180-day inpatient, outpatient, prescription, emergency room, and
      total costs were analyzed by ordinary least-squares and generalized linear model
      regressions, with selected costs further analyzed using two-part regression
      models. RESULTS: Among 830 patients referred to the TOC program, total healthcare
      costs at 180 days after discharge were an average of $2,139 lower than costs in
      the control group, yielding estimated savings of nearly $1.8 million for the
      managed care plan. CONCLUSION: Compared with usual postdischarge care, use of TOC
      services was associated with a significant reduction in 180-day total healthcare
      costs.

PMID- 29650727
TI  - A pharmacy-led United States Pharmacopeia (USP) chapter 800 compliance
      collaborative at an academic medical center.
AB  - PURPOSE: One academic medical center's efforts to move toward compliance with
      requirements of United States Pharmacopeia (USP) chapter 800 through a
      multidepartmental collaborative initiative are described. SUMMARY: Requirements
      of USP general chapter 800 (enforceable as of December 2019) address the handling
      of hazardous drugs (HDs) throughout the entire operational and clinical cycle,
      from receiving to compounding, administration, and waste disposal. Due to the
      variety of pharmacy operational areas in which HDs are encountered at University
      of North Carolina Medical Center (UNCMC), multiple pharmacy managers oversee the
      safe handling of HDs. To determine baseline compliance with USP chapter 800
      requirements, a common assessment tool was developed to ensure a standardized
      approach to compliance assessment in all areas. An interdepartmental workgroup
      was created to ensure institutionwide support for a collaborative compliance
      initiative, a uniform understanding of compliance risks, and robust action
      planning. UNCMC has taken a number of steps toward USP chapter compliance in
      areas such as engineering controls, environmental quality and controls, use of
      personal protective equipment, hazard communication programs, personnel training,
      spill control, and medical surveillance. CONCLUSION: Achieving USP chapter 800
      compliance presented several operational, clinical, and financial challenges for
      the medical center, requiring months of preparation and diligence by the hospital
      leadership. The pharmacy department-led compliance collaborative allowed
      departments to proactively align while implementing practice and quality
      standards to foster safety for patients, workers, and the environment.

PMID- 29650728
TI  - Metabolic strugGLS after FLT3 inhibition in AML.

PMID- 29650729
TI  - Venetoclax after idelalisib: relevant progress for CLL.

PMID- 29650730
TI  - Can genetics resolve what Notch does in HSCs?

PMID- 29650731
TI  - Lymphoma exosomes reprogram the bone marrow.

PMID- 29650732
TI  - Chemokines: a novel chronic GVHD target.

PMID- 29650733
TI  - ALK+ small cell variant of anaplastic large cell lymphoma with leukemic
      presentation.

PMID- 29650734
TI  - Monomorphic epitheliotropic intestinal T-cell lymphoma involving the central
      nervous system.

PMID- 29650735
TI  - A greater understanding.

PMID- 29650736
TI  - ?

PMID- 29650737
TI  - Approaches to primary care of adults with intellectual and developmental
      disabilities: Importance of frameworks for guidelines.

PMID- 29650738
TI  - Consumer inclusion: Experience of patients with intellectual and developmental
      disabilities informs primary care.

PMID- 29650739
TI  - ?

PMID- 29650740
TI  - Managing complexity in care of patients with intellectual and developmental
      disabilities: Natural fit for the family physician as an expert generalist.
AB  - OBJECTIVE: To delineate the factors inherent in caring for patients with
      intellectual and developmental disabilities (IDD) that lead to complexity and to
      provide perspectives and techniques mapped to the phases of the clinical
      encounter. SOURCES OF INFORMATION: The authors of the physical health section of
      the 2018 Canadian consensus guidelines on the primary care of adults with IDD
      consisted of family physicians, all of whom practise comprehensive family
      medicine with additional clinical experience in care of adults with IDD. These
      authors reviewed evidence on which their recommendations are based and these
      recommendations have undergone a rigorous peer review to ensure that they deserve
      special attention because they highlight what is different from what a family
      physician would consider to constitute "normal care" for the general population.
      MAIN MESSAGE: Additional factors across the phases of clinical encounters with
      patients with IDD include the need for the following: an initial assessment that
      identifies genetic or neurologic conditions to guide anticipatory care and
      isolates unique barriers to health promotion and chronic disease management;
      adaptations to history taking, particularly for patients who are unable to
      describe symptoms owing to cognitive and communication deficits; overcoming
      challenges to performing physical examinations and certain investigations;
      addressing uncertainty in the formulation of hypotheses to establish an
      appropriate diagnosis; and involvement of resources of the developmental services
      sector to provide a management plan as well as an adapted empathetic approach in
      order to integrate the patient's illness experience. CONCLUSION: Although each
      patient with IDD is unique, and care of patients with IDD requires knowledge of
      certain conditions, these considerations are readily identifiable, and family
      physicians as expert generalists are well equipped to provide excellent care to
      patients with IDD.

PMID- 29650741
TI  - HELP for behaviours that challenge in adults with intellectual and developmental
      disabilities.
AB  - OBJECTIVE: To provide primary care physicians with an understanding of the causes
      of behaviours that challenge (BTC) in adults with intellectual and developmental
      disabilities (IDD), as presented in the 2018 Canadian consensus guidelines for
      primary care of adults with IDD; to offer a systematic approach to the assessment
      and treatment of such behaviours; and to link to tools to support these
      assessments. SOURCES OF INFORMATION: This review elaborates upon guidelines 26 to
      29 in the mental health section of the 2018 Canadian consensus guidelines.
      Several of the authors participated in the development of these guidelines, which
      were based on literature searches and interdisciplinary input. MAIN MESSAGE: Most
      adults with IDD are followed by primary care providers but they comprise a small
      proportion of primary care practices. Unique ways of communicating needs,
      diagnostic queries, and BTC are common in this population. This complexity can
      lead to missed diagnoses and inappropriate antipsychotic medication use with
      attendant risks. This article presents a systematic approach, HELP, to the
      assessment and treatment of factors of Health, Environment, Lived experience, and
      Psychiatric conditions that can lead to BTC and includes tools to support these
      assessments. CONCLUSION: A structured approach to the assessment and treatment of
      BTC in adults with IDD helps family physicians provide guideline-directed,
      individualized care to this population. This includes a systematic evaluation
      using the HELP framework that takes place over multiple visits. A team of health
      professionals might be needed for optimal care, but these resources are not
      routinely available across Canada.

PMID- 29650742
TI  - Supporting adults with intellectual and developmental disabilities to participate
      in health care decision making.
AB  - OBJECTIVE: To discuss what is new in the revised guideline 3 of the "Primary care
      of adults with intellectual and developmental disabilities [IDD]. 2018 Canadian
      consensus guidelines" on decision-making capacity, and how to implement the
      recommendations. QUALITY OF EVIDENCE: Integrative review based on a literature
      search, the framework of the United Nations Convention on the Rights of Persons
      with Disabilities, and the experience of the authors. MAIN MESSAGE: Person
      centred health care of adults with IDD should include all possible contributions
      from the patient in decision making. At present, legal criteria do not address
      the relational aspects of decision making that are important for adults with IDD.
      The revised guideline 3 incorporates recent thinking regarding supported and
      shared decision making. It envisages decision making as a collaborative exercise
      in which the patient, trusted caregivers, and the family physician all are
      involved in deciding on medically appropriate interventions that promote the
      patient's goals or values. CONCLUSION: Family physicians and caregivers both play
      an important role in supporting adults with IDD so that they can participate in
      health care decision making. Communication, mediation, and advocacy skills, plus
      the use of tools adapted for adults with IDD, can facilitate the family
      physician's role.

PMID- 29650743
TI  - Improving transition to adulthood for adolescents with intellectual and
      developmental disabilities: Proactive developmental and systems perspective.
AB  - OBJECTIVE: To demonstrate how family physicians can contribute to a piece of the
      journey of improving quality-of-life outcomes for people with intellectual and
      developmental disabilities (IDD) when they undergo the transition from
      adolescence to adulthood. SOURCES OF INFORMATION: The "Primary care of adults
      with intellectual and developmental disabilities. 2018 Canadian consensus
      guidelines" literature review and interdisciplinary input. MAIN MESSAGE: Family
      physicians should be proactive in anticipating and supporting the transition of
      people with IDD from adolescence to adulthood. Interventions should be guided by
      a developmental perspective regarding the person with IDD and a life-cycle
      approach to supporting families. Family physicians also have a role in helping
      people with IDD and their families to navigate successfully through changing
      community-based support systems in their province, especially health care and
      social services systems. Therefore, family physicians should be aware of current
      services available in their regions. CONCLUSION: Community and team-based family
      physicians can optimize the quality of life of people with IDD and their families
      by adopting a proactive developmental and systems approach to preparing youth
      with IDD for adulthood. In doing so, they exemplify the 4 principles of family
      medicine.

PMID- 29650744
TI  - Health checks for adults with intellectual and developmental disabilities in a
      family practice.
AB  - OBJECTIVE: To provide tips and tools for primary care practitioners carrying out
      health checks for adult patients with intellectual and developmental disabilities
      (IDD) and for implementing a systematic program of health checks in a group or
      team practice. SOURCES OF INFORMATION: The "Primary Care of Adults with
      Intellectual and Developmental Disabilities. 2018 Canadian Consensus Guidelines"
      literature review and interdisciplinary input. Experience in implementing health
      checks in family practices was obtained through the primary care project of H
      CARDD (Health Care Access Research and Developmental Disabilities). MAIN MESSAGE:
      Annual comprehensive health assessments ("health checks") are a recommendation of
      the 2018 Canadian consensus guidelines for primary care of adults with IDD
      because of evidence of benefit in this population. Although health checks might
      require more time to complete for people with IDD than is usual for encounters in
      primary care, family physicians are in an ideal position to provide this service
      because of the attributes of family medicine, which include both an orientation
      to proactive care and the ability to provide continuity of care. Tips and tools
      are provided for carrying out health checks for adult patients with IDD and for
      implementing a systematic program of health checks in a group or team practice.
      CONCLUSION: Health checks can help enhance a family physician's approach to
      providing care for adults with IDD.

PMID- 29650745
TI  - Circles of care for people with intellectual and developmental disabilities:
      Communication, collaboration, and coordination.
AB  - OBJECTIVE: To review health information exchange (HIE) processes that affect the
      health of people with intellectual and developmental disabilities (IDD) and to
      suggest practical tips and strategies for communicating, collaborating, and
      coordinating in the primary care setting. SOURCES OF INFORMATION: The "Primary
      care of adults with intellectual and developmental disabilities. 2018 Canadian
      consensus guidelines" literature review and interdisciplinary input. MAIN
      MESSAGE: Disparities exist between the provision of health care for the general
      population and that for people with IDD. These disparities are due in part to
      gaps in HIE. Health information exchange involves documenting, collecting, and
      disseminating a patient's health information. In exploring ways to improve HIE
      for people with IDD, the communication skills of the family physician are
      considered in the context of the triad that includes the patient, his or her
      caregivers, and the family physician. The framework of the Patient's Medical Home
      is used in exploring these processes, and various strategies are offered for
      communicating, collaborating, and coordinating health care that can be
      implemented by family physicians in order to narrow the gaps in care that exist
      for people with IDD. CONCLUSION: Improvements in HIE by communicating,
      collaborating, and coordinating health care better will improve health outcomes
      for people with IDD.

PMID- 29650746
TI  - Comprehensive preventive care assessments for adults with intellectual and
      developmental disabilities: Part 1: How do we know if it is happening?
AB  - OBJECTIVE: To determine how best to measure the provision of comprehensive
      preventive care assessment of adults with intellectual and developmental
      disabilities (IDD). DESIGN: Cross-sectional study. SETTING: Ontario.
      PARTICIPANTS: Adults with IDD between 40 and 64 years of age in 2013 and 2014.
      MAIN OUTCOME MEASURES: Health examination was defined using the Ontario Health
      Insurance Plan billing data fee code A003 (with diagnostic code 917 or 319) or
      fee code K131, and the Primary Care Quality Composite Score (PCQS), a measure
      combining 7 different screening maneuvers (lipid, glucose, breast cancer,
      cervical cancer, colorectal cancer, eye, and hemoglobin A1c screening), was
      identified using administrative health data. RESULTS: A total of 28 825 adults
      with IDD were identified in 2013 and 2014. Overall, 12.1% of adults with IDD
      received a health examination; 51.2% received a high (>= 0.6) PCQS. Male patients
      were more likely to have received all of their eligible screening maneuvers if
      they had had a health examination compared with female patients (odds ratio of
      5.73 vs 3.99, respectively). CONCLUSION: Less than 60% of adults with IDD appear
      to be receiving comprehensive preventive care. Future studies assessing the
      quality of preventive care received by adults with IDD should combine health
      examination billing codes and the PCQS.

PMID- 29650747
TI  - Patient-centred primary care of adults with severe and profound intellectual and
      developmental disabilities: Patient-caregiver-physician relationship.
AB  - OBJECTIVE: To explore the process of the development of the patient-physician
      relationship in adult patients with severe or profound intellectual and
      developmental disabilities (IDD), from the perspective of the patients'
      caregivers. DESIGN: Constructivist grounded theory. SETTING: St John's, NL.
      PARTICIPANTS: Thirteen primary caregivers (5 males, 8 females) of 1 or more
      adults with severe or profound IDD. METHODS: Data were collected via in-depth,
      semistructured interviews conducted in person or by telephone. Interviews were
      audiorecorded and transcribed verbatim. Field notes were documented immediately
      by the interviewer and discussed with the research team. Memos in the form of
      reflective notes served as additional sources of data. MAIN FINDINGS: From the
      perspective of the caregivers, the core process in the development of the patient
      physician relationship was protection. This process began as a result of the
      caregiver's recognition of the patient's vulnerability and moved through a number
      of stages before resulting in the development of a dynamic triangular interaction
      between the patient, caregiver, and family physician. First, the caregiver
      provides extreme nurturing to the patient, which results in the development of a
      strong bond between them. The patient and caregiver approached the family
      physician together as one unit, and then decided together on whether or not to
      open the patient-caregiver bond to the physician. The resultant dynamic
      triangular interaction formed the starting point from which 1 of 4 different
      relationship-development trajectories began. Which trajectory was taken and,
      therefore, the character of the relationships that developed was determined by
      how the caregiver and patient experienced their interaction with the family
      physician. CONCLUSION: Findings highlight the process of protection and the
      centrality of the patient-caregiver bond within the development of a triadic
      relationship involving the patient with IDD, the caregiver, and the family
      physician. How a physician approaches this bond can influence the trajectory of
      the resulting relationship.

PMID- 29650749
TI  - Hello from the other side: Parental reflections on the patient-parent-family
      physician triadic relationship.

PMID- 29650748
TI  - Exploring the prenatal experience of women with intellectual and developmental
      disabilities: In a southeastern Ontario family health team.
AB  - OBJECTIVE: To identify psychosocial challenges facing pregnant women with
      intellectual and developmental disabilities (IDD) using retrospective, routinely
      collected electronic medical record data. DESIGN: A retrospective qualitative
      study using narratives and supporting documents found in the electronic medical
      record of an academic family health team (FHT). SETTING: Academic FHT in
      southeastern Ontario. PARTICIPANTS: A sample of 10 women with a diagnosis of IDD,
      rostered to physicians at the academic FHT, who delivered a child between January
      2010 and June 2015 (14 pregnancies). Exclusion criteria included women who
      received prenatal care from a midwife and women for whom no delivery or antenatal
      records were available. METHODS: Thematic analysis of data collected from a
      retrospective chart review. MAIN FINDINGS: Many women with IDD had yes marked on
      their antenatal records for poor social supports, family violence, and parenting
      concerns. Women with IDD had pregnancies that were characterized by complex
      social environments, financial instability, discord between their perceptions and
      their physicians' perceptions, and stressful encounters with Child and Family
      Services. CONCLUSION: Findings in this study support previous research that
      pregnant women with IDD are a vulnerable population, at higher risk of adverse
      health outcomes. There is a need for specific care guidelines for health care
      providers, as well as additional resources and social supports.

PMID- 29650750
TI  - BRAF and MEK Inhibitors Increase PD-1-Positive Melanoma Cells Leading to a
      Potential Lymphocyte-Independent Synergism with Anti-PD-1 Antibody.
AB  - Purpose: BRAF and MEK inhibitors (BRAF/MEKi) favor melanoma-infiltrating
      lymphocytes, providing the rationale for current combinatorial trials with anti
      PD-1 antibody. A portion of melanoma cells may express PD-1, and anti-PD-1
      antibody could have a direct antitumor effect. Here, we explore whether BRAF/MEKi
      modulate rates of PD-1+ melanoma cells, supporting an additional-lymphocyte
      independent-basis for their therapeutic combination with anti-PD-1
      antibody.Experimental Design: With data mining and flow cytometry, we assessed PD
      1, PD-L1/2 expression on melanoma cell lines (CCLE, N = 61; validation cell
      lines, N = 7) and melanoma tumors (TCGA, N = 214). We explored in vitro how
      BRAF/MEKi affect rates of PD-1+, PD-L1/2+ melanoma cells, and characterized the
      proliferative and putative stemness features of PD-1+ melanoma cells. We tested
      the functional lymphocyte-independent effect of anti-PD-1 antibody alone and in
      combination with BRAF/MEKi in vitro and in an in vivo immunodeficient murine
      model.Results: PD-1 is consistently expressed on a small subset of melanoma
      cells, but PD-1+ cells increase to relevant rates during BRAF/MEKi treatment
      [7.3% (5.6-14.2) vs. 1.5% (0.7-3.2), P = 0.0156; N = 7], together with PD-L2+
      melanoma cells [8.5% (0.0-63.0) vs. 1.5% (0.2-43.3), P = 0.0312; N = 7]. PD-1+
      cells proliferate less than PD-1- cells (avg. 65% less; t = 7 days) and are
      preferentially endowed with stemness features. In vivo, the direct anti-melanoma
      activity of PD-1 blockage as monotherapy was negligible, but its association with
      BRAF/MEKi significantly delayed the development of drug resistance and tumor
      relapse.Conclusions: BRAF/MEKi increase the rates of PD-1+ melanoma cells that
      may sustain tumor relapse, providing a lymphocyte-independent rationale to
      explore combinatory strategies with anti-PD-1 antibody. Clin Cancer Res; 24(14);
      3377-85. (c)2018 AACR.

PMID- 29650751
TI  - FDA Approval Summary: Niraparib for the Maintenance Treatment of Patients with
      Recurrent Ovarian Cancer in Response to Platinum-Based Chemotherapy.
AB  - The FDA approved niraparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, on
      March 27, 2017, for maintenance treatment of patients with recurrent epithelial
      ovarian, fallopian tube, or primary peritoneal cancer who are in response to
      platinum-based chemotherapy. Approval was based on data from the NOVA trial
      comparing niraparib with placebo in two independent cohorts, based on germline
      BRCA mutation status (gBRCAm vs. non-gBRCAm). Progression-free survival (PFS) in
      each cohort was the primary endpoint. In the gBRCAm cohort, estimated median PFS
      on niraparib was 21 months versus 5.5 months on placebo [HR, 0.26; 95% confidence
      interval (CI), 0.17-0.41; P < 0.0001]. In the non-gBRCAm cohort, estimated median
      PFS for niraparib and placebo was 9.3 and 3.9 months, respectively (HR, 0.45; 95%
      CI, 0.34-0.61; P < 0.0001). Common adverse reactions (>20% and higher incidence
      in the niraparib arm) with niraparib included thrombocytopenia, anemia,
      neutropenia, nausea, constipation, vomiting, mucositis, fatigue, decreased
      appetite, headache, insomnia, nasopharyngitis, dyspnea, rash, and hypertension.
      There were five cases of myelodysplastic syndrome and acute myeloid leukemia
      (1.4%) in patients treated with niraparib compared with two cases (1.1%) on
      placebo. Niraparib is the first PARP inhibitor approved as maintenance therapy
      for patients with ovarian, fallopian tube, or primary peritoneal cancer, with
      improvement in PFS, regardless of gBRCAm status. Clin Cancer Res; 24(17); 4066
      71. (c)2018 AACRSee related commentary by Konstantinopoulos and Matulonis, p.
      4062.

PMID- 29650753
TI  - Polarized object detection in crabs: a two-channel system.
AB  - Many animal species take advantage of polarization vision for vital tasks such as
      orientation, communication and contrast enhancement. Previous studies have
      suggested that decapod crustaceans use a two-channel polarization system for
      contrast enhancement. Here, we characterize the polarization contrast sensitivity
      in a grapsid crab. We estimated the polarization contrast sensitivity of the
      animals by quantifying both their escape response and changes in heart rate when
      presented with polarized motion stimuli. The motion stimulus consisted of an
      expanding disk with an 82 deg polarization difference between the object and the
      background. More than 90% of animals responded by freezing or trying to avoid the
      polarized stimulus. In addition, we co-rotated the electric vector (e-vector)
      orientation of the light from the object and background by increments of 30 deg
      and found that the animals' escape response varied periodically with a 90 deg
      period. Maximum escape responses were obtained for object and background e
      vectors near the vertical and horizontal orientations. Changes in cardiac
      response showed parallel results but also a minimum response when e-vectors of
      object and background were shifted by 45 deg with respect to the maxima. These
      results are consistent with an orthogonal receptor arrangement for the detection
      of polarized light, in which two channels are aligned with the vertical and
      horizontal orientations. It has been hypothesized that animals with object-based
      polarization vision rely on a two-channel detection system analogous to that of
      color processing in dichromats. Our results, obtained by systematically varying
      the e-vectors of object and background, provide strong empirical support for this
      theoretical model of polarized object detection.

PMID- 29650752
TI  - Lipid transfer proteins in the assembly of apoB-containing lipoproteins.
AB  - A better understanding of intracellular lipoprotein assembly may help identify
      proteins with important roles in lipid disorders. apoB-containing lipoproteins (B
      lps) are macromolecular lipid and protein micelles that act as specialized
      transport vehicles for hydrophobic lipids. They are assembled predominantly in
      enterocytes and hepatocytes to transport dietary and endogenous fat,
      respectively, to different tissues. Assembly occurs in the endoplasmic reticulum
      (ER) and is dependent on lipid resynthesis in the ER and on a chaperone, namely,
      microsomal triglyceride transfer protein (MTTP). Precursors for lipid synthesis
      are obtained from extracellular sources and from cytoplasmic lipid droplets. MTTP
      is the major and essential lipid transfer protein that transfers phospholipids
      and triacylglycerols to nascent apoB for the assembly of lipoproteins. Assembly
      is aided by cell death-inducing DFF45-like effector B and by phospholipid
      transfer protein, which may facilitate additional deposition of triacylglycerols
      and phospholipids, respectively, to apoB. Here, we summarize the current
      understanding of the different steps in the assembly of B-lps and discuss the
      role of lipid transfer proteins in these steps to help identify new clinical
      targets for lipid-associated disorders, such as heart disease.

PMID- 29650754
TI  - Reduced non-bicarbonate skeletal muscle buffering capacity in mice with the mini
      muscle phenotype.
AB  - Muscle pH decreases during exercise, which may impair function. Endurance
      training typically reduces muscle buffering capacity as a result of changes in
      fiber-type composition, but existing comparisons of species that vary in activity
      level are ambiguous. We hypothesized that high-runner (HR) lines of mice from an
      experiment that breeds mice for voluntary wheel running would have altered muscle
      buffering capacity as compared with their non-selected control counterparts. We
      also expected that 6 days of wheel access, as used in the selection protocol,
      would reduce buffering capacity, especially for HR mice. Finally, we expected a
      subset of HR mice with the 'mini-muscle' phenotype to have relatively low
      buffering capacity as a result of fewer type IIb fibers. We tested non
      bicarbonate buffering capacity of thigh muscles. Only HR mice expressing the mini
      muscle phenotype had significantly reduced buffering capacity, females had lower
      buffering capacity than males, and wheel access had no significant effect.

PMID- 29650755
TI  - Thermosensory perception regulates speed of movement in response to temperature
      changes in Drosophila melanogaster.
AB  - Temperature influences the physiology and behavior of all organisms. For
      ectotherms, which lack central temperature regulation, temperature adaptation
      requires sheltering from or moving to a heat source. As temperature constrains
      the rate of metabolic reactions, it can directly affect ectotherm physiology and
      thus behavioral performance. This direct effect is particularly relevant for
      insects, as their small bodies readily equilibrate with ambient temperature. In
      fact, models of enzyme kinetics applied to insect behavior predict performance at
      different temperatures suggesting that thermal physiology governs behavior.
      However, insects also possess thermosensory neurons critical for locating
      preferred temperatures, showing cognitive control. This suggests that temperature
      related behavior can emerge directly from a physiological effect, indirectly as a
      consequence of thermosensory processing, or through a combination of both. To
      separate the roles of thermal physiology and cognitive control, we developed an
      arena that allows fast temperature changes in time and space, and in which
      animals' movements are automatically quantified. We exposed wild-type Drosophila
      melanogaster and thermosensory receptor mutants to a dynamic temperature
      environment and tracked their movements. The locomotor speed of wild-type flies
      closely matched models of enzyme kinetics, but the behavior of thermosensory
      mutants did not. Mutations in thermosensory receptor gene dTrpA1 (Transient
      Receptor Potential A1) expressed in the brain resulted in a complete lack of
      response to temperature changes, while mutations in peripheral thermosensory
      receptor gene Gr28b(D) resulted in a diminished response. We conclude that flies
      react to temperature through cognitive control, informed by interactions between
      various thermosensory neurons, the behavioral output of which resembles models of
      enzyme kinetics.

PMID- 29650756
TI  - IGF-1 induces SOCS-2 but not SOCS-1 and SOCS-3 transcription in juvenile Nile
      tilapia (Oreochromis niloticus).
AB  - Insulin-like growth factor-1 (IGF-1) plays a crucial role in regulating growth in
      vertebrates whereas suppressors of cytokine signaling (SOCS) act as feedback
      inhibitors of the GH/IGF-1 axis. Although SOCS-2 binds the IGF-1 receptor and
      inhibits IGF-1-induced STAT3 activation, presently there is no clear evidence as
      to whether IGF-1 could induce SOCS gene expression. The current study aimed to
      determine whether IGF-1 could induce the transcription of SOCS in juvenile Nile
      tilapia (Oreochromis niloticus). We show that there is a common positive
      relationship between the mRNA expression of IGF-I and SOCS-2 under different
      nutritional statuses and stimulants, but not the mRNA expression of SOCS-1 and
      SOCS-3 Furthermore, rhIGF-1 treatment and transcriptional activity assay
      confirmed the hypothesis that IGF-1 could induce SOCS-2 expression, whereas it
      had no effect or even decreased the expression of SOCS-1 and SOCS-3 Overall, we
      obtained evidence that the transcription of SOCS-2, but not SOCS-1 or SOCS-3,
      could be induced by IGF signaling, suggesting that SOCS-2 serves as a feedback
      suppressor of the IGF-1 axis in juvenile Nile tilapia.

PMID- 29650757
TI  - Conformational flexibility within the nascent polypeptide-associated complex
      enables its interactions with structurally diverse client proteins.
AB  - As newly synthesized polypeptides emerge from the ribosome, it is crucial that
      they fold correctly. To prevent premature aggregation, nascent chains interact
      with chaperones that facilitate folding or prevent misfolding until protein
      synthesis is complete. Nascent polypeptide-associated complex (NAC) is a ribosome
      associated chaperone that is important for protein homeostasis. However, how NAC
      binds its substrates remains unclear. Using native electrospray ionization MS
      (ESI-MS), limited proteolysis, NMR, and cross-linking, we analyzed the
      conformational properties of NAC from Caenorhabditis elegans and studied its
      ability to bind proteins in different conformational states. Our results revealed
      that NAC adopts an array of compact and expanded conformations and binds weakly
      to client proteins that are unfolded, folded, or intrinsically disordered,
      suggestive of broad substrate compatibility. Of note, we found that this weak
      binding retards aggregation of the intrinsically disordered protein alpha
      synuclein both in vitro and in vivo These findings provide critical insights into
      the structure and function of NAC. Specifically, they reveal the ability of NAC
      to exploit its conformational plasticity to bind a repertoire of substrates with
      unrelated sequences and structures, independently of actively translating
      ribosomes.

PMID- 29650759
TI  - The NHS at 70: Loved, valued, and affordable.

PMID- 29650758
TI  - The fructose-2,6-bisphosphatase TIGAR suppresses NF-kappaB signaling by directly
      inhibiting the linear ubiquitin assembly complex LUBAC.
AB  - The systems integration of whole-body metabolism and immune signaling are central
      homeostatic mechanisms necessary for maintenance of normal physiology, and
      dysregulation of these processes leads to a variety of chronic disorders.
      However, the intracellular mechanisms responsible for cell-autonomous cross-talk
      between the inflammatory signaling pathways and metabolic flux have remained
      enigmatic. In this study, we discovered that the fructose-2,6-bisphosphatase
      TIGAR (Tp53-induced glycolysis and apoptosis regulator) critically regulates NF
      kappaB activation. We found that TIGAR potently inhibits NF-kappaB-dependent gene
      expression by suppressing the upstream activation of IKKbeta phosphorylation and
      kinase activation. This inhibition occurred through a direct binding competition
      between NEMO and TIGAR for association with the linear ubiquitination assembly
      complex (LUBAC). This competition prevented linear ubiquitination of NEMO, which
      is required for activation of IKKbeta and other downstream targets. Furthermore,
      a TIGAR phosphatase activity-deficient mutant was equally effective as WT TIGAR
      in inhibiting NEMO linear ubiquitination, IKKbeta phosphorylation/activation, and
      NF-kappaB signaling, indicating that TIGAR's effect on NF-kappaB signaling is due
      to its interaction with LUBAC. Physiologically, TIGAR knockout mice displayed
      enhanced adipose tissue NF-kappaB signaling, whereas adipocyte-specific
      overexpression of TIGAR suppressed adipose tissue NF-kappaB signaling. Together,
      these results demonstrate that TIGAR has a nonenzymatic molecular function that
      modulates the NF-kappaB signaling pathway by directly inhibiting the E3 ligase
      activity of LUBAC.

PMID- 29650760
TI  - So not mothers: responsibility for surrogate orphans.
AB  - The law ordinarily recognises the woman who gives birth as the mother of a child,
      but in certain jurisdictions, it will recognise the commissioning couple as the
      legal parents of a child born to a commercial surrogate. Some commissioning
      parents have, however, effectively abandoned the children they commission, and in
      such cases, commercial surrogates may find themselves facing unexpected maternal
      responsibility for children they had fully intended to give up. Any assumption
      that commercial surrogates ought to assume maternal responsibility for abandoned
      children runs contrary to the moral suppositions that typically govern contract
      surrogacy, in particular, assumptions that gestational carriers are not 'mothers'
      in any morally significant sense. In general, commercial gestational surrogates
      are almost entirely conceptualised as 'vessels'. In a moral sense, it is deeply
      inconsistent to expect commercial surrogates to assume maternal responsibility
      simply because commissioning parents abandon children for one reason or another.
      We identify several instances of child abandonment and discuss their implications
      with regard to the moral conceptualisation of commercial gestational surrogates.
      We conclude that if gestational surrogates are to remain conceptualised as mere
      vessels, they should not be expected to assume responsibility for children
      abandoned by commissioning parents, not even the limited responsibility of giving
      them up for adoption or surrendering them to the state.

PMID- 29650761
TI  - Once-daily triple therapy inhaler for COPD.
AB  - ?Trelegy Ellipta (GSK) is a dry powder inhaler containing fluticasone furoate
      (inhaled corticosteroid [ICS]), vilanterol trifenatate (long-acting beta2 agonist
      [LABA]) and umeclidinium bromide (long-acting muscarinic antagonist [LAMA]).1 It
      is licensed for once-daily use as maintenance treatment for adults with moderate
      to severe chronic obstructive pulmonary disease (COPD) who are not adequately
      treated by a combination of an ICS and a LABA. Here, we consider the evidence for
      this combination product and discuss how it fits with current management
      strategies.

PMID- 29650762
TI  - High-dose antihistamines for chronic spontaneous urticaria in adults.
AB  - Chronic spontaneous urticaria (CSU) is a common skin disease characterised by
      intermittent weals (hives), angioedema or both lasting for at least 6 weeks.1-3
      Second-generation antihistamines are widely used to manage symptoms but are not
      completely effective in many patients at licensed doses.4 Some guidelines
      recommend off-label use of high-dose antihistamines as the next therapeutic
      step.2,3 Here, we review the evidence supporting this recommendation.

PMID- 29650765
TI  - Prospective Cardiovascular Genetics Evaluation in Spontaneous Coronary Artery
      Dissection.
AB  - BACKGROUND: Previous studies describing genetics evaluation in spontaneous
      coronary artery dissection (SCAD) have been retrospective in nature or presented
      as single case reports. As part of a dedicated clinical program, we evaluated
      patients in cardiovascular genetics clinic to determine the role of genetically
      triggered vascular disease and genetic testing in SCAD. METHODS AND RESULTS:
      Patient data were entered prospectively into the Massachusetts General Hospital
      SCAD registry database from July 2013 to September 2017. Clinically indicated
      genetic testing was conducted based on patient imaging, family history, physical
      examination, and patient preference. Of the 107 patients enrolled in the
      registry, 73 underwent cardiovascular genetics evaluation at our center (average
      age, 45.3+/-9.4 years; 85.3% female), and genetic testing was performed for 44
      patients. A family history of aneurysm or dissection was not a prevalent feature
      in the study population, and only 1 patient had a family history of SCAD. Six
      patients (8.2%) had identifiable genetically triggered vascular disease: 3 with
      vascular Ehlers-Danlos syndrome (COL3A1), 1 with Nail-patella syndrome (LMX1B), 1
      with autosomal dominant polycystic kidney disease (PKD1), and 1 with Loeys-Dietz
      syndrome (SMAD3). None of these 6 had radiographic evidence of fibromuscular
      dysplasia. CONCLUSIONS: In this series, 8.2% of the SCAD patients evaluated had a
      molecularly identifiable disorder associated with vascular disease. The most
      common diagnosis was vascular Ehlers-Danlos syndrome. Patients with positive gene
      testing were significantly younger at the time of their first SCAD event. A low
      threshold for genetic testing should be considered in patients with SCAD.

PMID- 29650766
TI  - Association of Genetic Instrumental Variables for Lung Function on Coronary
      Artery Disease Risk: A 2-Sample Mendelian Randomization Study.
AB  - BACKGROUND: Lung function, assessed by forced expiratory volume in 1 second
      (FEV1) and forced vital capacity (FVC), is inversely associated with coronary
      artery disease (CAD), but these associations could be because of confounding or
      reversed causality. We conducted a 2-sample Mendelian randomization study, using
      publicly available data from relevant genome-wide association studies, to examine
      the role of FEV1 or FVC on CAD. METHODS: We used the most recent genome-wide
      association studies on lung function to extract genetic instruments related to
      FEV1 and FVC (n=92 749). Data on the association between genetic instruments and
      CAD were obtained from Coronary Artery Disease Genome wide Replication and Meta
      analysis plus The Coronary Artery Disease Genetics 1000 Genomes-based genome-wide
      association studies (60 801 CAD cases and 123 504 controls). We used inverse
      variance weighting with a multiplicative random effect to estimate the genetic
      instrumented association of FEV1 and FVC on CAD. Sensitivity analyses included
      weighted median and MR-Egger methods. RESULTS: Each SD greater FEV1 was
      associated with a lower risk of CAD (odds ratio, 0.78 per SD; 95% confidence
      interval, 0.62-0.98) with a similar magnitude for FVC on CAD risk (odds ratio,
      0.82 per SD; 95% confidence interval, 0.64-1.06). Estimates for FEV1 were similar
      when using MR-Egger method (odds ratio, 0.80 per SD; 95% confidence interval,
      0.33-1.94) although the magnitude was smaller for weighted median method (odds
      ratio, 0.93 per SD; 95% confidence interval, 0.75-1.17). Estimates for FVC in the
      sensitivity analyses were attenuated (median) or changed direction (MR-Egger).
      CONCLUSIONS: Our study suggested an inverse relation between FEV1 and CAD, but
      for FVC, evidence is less clear.

PMID- 29650767
TI  - Letter by Ma et al Regarding Article, "Novel Mutation in FLNC (Filamin C) Causes
      Familial Restrictive Cardiomyopathy".

PMID- 29650764
TI  - Genetic Variants Influencing Plasma Renin Activity in Hypertensive Patients From
      the PEAR Study (Pharmacogenomic Evaluation of Antihypertensive Responses).
AB  - BACKGROUND: Plasma renin is an important regulator of blood pressure (BP). Plasma
      renin activity (PRA) has been shown to correlate with variability in BP response
      to antihypertensive agents. We conducted a genome-wide association study to
      identify single-nucleotide polymorphisms (SNPs) associated with baseline PRA
      using data from the PEAR study (Pharmacogenomic Evaluation of Antihypertensive
      Responses). METHODS: Multiple linear regression analysis was performed in 461
      whites and 297 blacks using an additive model, adjusting for age, sex, and
      ancestry-specific principal components. Top SNPs were prioritized by testing the
      expected direction of association for BP response to atenolol and
      hydrochlorothiazide. Top regions from the BP response prioritization were tested
      for functional evidence through differences in gene expression by genotype using
      RNA sequencing data. Regions with functional evidence were assessed for
      replication with baseline PRA in an independent study (PEAR-2). RESULTS: Our top
      SNP rs3784921 was in the SNN-TXNDC11 gene region. The G allele of rs3784921 was
      associated with higher baseline PRA (beta=0.47; P=2.09*10-6) and smaller systolic
      BP reduction in response to hydrochlorothiazide (beta=2.97; 1-sided P=0.006). In
      addition, TXNDC11 expression differed by rs3784921 genotype (P=0.007), and
      rs1802409, a proxy SNP for rs3784921 (r2=0.98-1.00), replicated in PEAR-2
      (beta=0.15; 1-sided P=0.038). Additional SNPs associated with baseline PRA that
      passed BP response prioritization were in/near the genes CHD9, XIRP2, and GHR.
      CONCLUSIONS: We identified multiple regions associated with baseline PRA that
      were prioritized through BP response signals to 2 mechanistically different
      antihypertensive drugs. CLINICAL TRIAL REGISTRATION: URL:
      https://www.clinicaltrials.gov. Unique identifier: NCT00246519.

PMID- 29650768
TI  - Lung Function and Coronary Artery Disease Risk.

PMID- 29650769
TI  - Is Plasma Renin Activity Genetically Determined and How Much Does It Matter for
      Treating Hypertension?

PMID- 29650770
TI  - Response by Ma et al to Letter Regarding Article, "Novel Mutation in FLNC
      (Filamin C) Causes Familial Restrictive Cardiomyopathy".

PMID- 29650771
TI  - Genetics of Spontaneous Coronary Artery Dissection Gains New Momentum.

PMID- 29650772
TI  - Branched-Chain Amino Acids: The Metabolic Link Between Type 2 Diabetes Mellitus
      and Cardiovascular Disease?

PMID- 29650773
TI  - Cannabinoid Type 1 Receptors Are Upregulated During Acute Activation of Brown
      Adipose Tissue.
AB  - Activating brown adipose tissue (BAT) could provide a potential approach for the
      treatment of obesity and metabolic disease in humans. Obesity is associated with
      upregulation of the endocannabinoid system, and blocking the cannabinoid type 1
      receptor (CB1R) has been shown to cause weight loss and to decrease
      cardiometabolic risk factors. These effects may be mediated partly via increased
      BAT metabolism, since there is evidence that CB1R antagonism activates BAT in
      rodents. To investigate the significance of CB1R in BAT function, we quantified
      the density of CB1R in human and rodent BAT using the positron emission
      tomography radioligand [18F]FMPEP-d2 and measured BAT activation in parallel with
      the glucose analog [18F]fluorodeoxyglucose. Activation by cold exposure markedly
      increased CB1R density and glucose uptake in the BAT of lean men. Similarly,
      beta3-receptor agonism increased CB1R density in the BAT of rats. In contrast,
      overweight men with reduced BAT activity exhibited decreased CB1R in BAT,
      reflecting impaired endocannabinoid regulation. Image-guided biopsies confirmed
      CB1R mRNA expression in human BAT. Furthermore, CB1R blockade increased glucose
      uptake and lipolysis of brown adipocytes. Our results highlight that CB1Rs are
      significant for human BAT activity, and the CB1Rs provide a novel therapeutic
      target for BAT activation in humans.

PMID- 29650774
TI  - Genetic Variants in CPA6 and PRPF31 Are Associated With Variation in Response to
      Metformin in Individuals With Type 2 Diabetes.
AB  - Metformin is the first-line treatment for type 2 diabetes (T2D). Although widely
      prescribed, the glucose-lowering mechanism for metformin is incompletely
      understood. Here, we used a genome-wide association approach in a diverse group
      of individuals with T2D from the Action to Control Cardiovascular Risk in
      Diabetes (ACCORD) clinical trial to identify common and rare variants associated
      with HbA1c response to metformin treatment and followed up these findings in four
      replication cohorts. Common variants in PRPF31 and CPA6 were associated with
      worse and better metformin response, respectively (P < 5 * 10-6), and meta
      analysis in independent cohorts displayed similar associations with metformin
      response (P = 1.2 * 10-8 and P = 0.005, respectively). Previous studies have
      shown that PRPF31(+/-) knockout mice have increased total body fat (P = 1.78 * 10
      6) and increased fasted circulating glucose (P = 5.73 * 10-6). Furthermore, rare
      variants in STAT3 associated with worse metformin response (q <0.1). STAT3 is a
      ubiquitously expressed pleiotropic transcriptional activator that participates in
      the regulation of metabolism and feeding behavior. Here, we provide novel
      evidence for associations of common and rare variants in PRPF31, CPA6, and STAT3
      with metformin response that may provide insight into mechanisms important for
      metformin efficacy in T2D.

PMID- 29650775
TI  - Mechanotransduction via the LINC complex regulates DNA replication in myonuclei.
AB  - Nuclear mechanotransduction has been implicated in the control of chromatin
      organization; however, its impact on functional contractile myofibers is unclear.
      We found that deleting components of the linker of nucleoskeleton and
      cytoskeleton (LINC) complex in Drosophila melanogaster larval muscles abolishes
      the controlled and synchronized DNA endoreplication, typical of nuclei across
      myofibers, resulting in increased and variable DNA content in myonuclei of
      individual myofibers. Moreover, perturbation of LINC-independent mechanical input
      after knockdown of beta-Integrin in larval muscles similarly led to increased DNA
      content in myonuclei. Genome-wide RNA-polymerase II occupancy analysis in
      myofibers of the LINC mutant klar indicated an altered binding profile, including
      a significant decrease in the chromatin regulator barrier-to-autointegration
      factor (BAF) and the contractile regulator Troponin C. Importantly, muscle
      specific knockdown of BAF led to increased DNA content in myonuclei, phenocopying
      the LINC mutant phenotype. We propose that mechanical stimuli transmitted via the
      LINC complex act via BAF to regulate synchronized cell-cycle progression of
      myonuclei across single myofibers.

PMID- 29650778
TI  - REPLY.

PMID- 29650779
TI  - Increasing the Accuracy of Optic Nerve Measurement Using 3D Volumetry.

PMID- 29650777
TI  - MLL leukemia induction by t(9;11) chromosomal translocation in human
      hematopoietic stem cells using genome editing.
AB  - Genome editing provides a potential approach to model de novo leukemogenesis in
      primary human hematopoietic stem and progenitor cells (HSPCs) through induction
      of chromosomal translocations by targeted DNA double-strand breaks. However, very
      low efficiency of translocations and lack of markers for translocated cells serve
      as barriers to their characterization and model development. Here, we used
      transcription activator-like effector nucleases to generate t(9;11) chromosomal
      translocations encoding MLL-AF9 and reciprocal AF9-MLL fusion products in CD34+
      human cord blood cells. Selected cytokine combinations enabled monoclonal
      outgrowth and immortalization of initially rare translocated cells, which were
      distinguished by elevated MLL target gene expression, high surface CD9
      expression, and increased colony-forming ability. Subsequent transplantation into
      immune-compromised mice induced myeloid leukemias within 48 weeks, whose
      pathologic and molecular features extensively overlap with de novo patient MLL
      rearranged leukemias. No secondary pathogenic mutations were revealed by targeted
      exome sequencing and whole genome RNA-sequencing analyses, suggesting the genetic
      sufficiency of t(9;11) translocation for leukemia development from human HSPCs.
      Thus, genome editing enables modeling of human acute MLL-rearranged leukemia in
      vivo, reflecting the genetic simplicity of this disease, and provides an
      experimental platform for biological and disease-modeling applications.

PMID- 29650776
TI  - Lymphatic exosomes promote dendritic cell migration along guidance cues.
AB  - Lymphatic endothelial cells (LECs) release extracellular chemokines to guide the
      migration of dendritic cells. In this study, we report that LECs also release
      basolateral exosome-rich endothelial vesicles (EEVs) that are secreted in greater
      numbers in the presence of inflammatory cytokines and accumulate in the
      perivascular stroma of small lymphatic vessels in human chronic inflammatory
      diseases. Proteomic analyses of EEV fractions identified >1,700 cargo proteins
      and revealed a dominant motility-promoting protein signature. In vitro and ex
      vivo EEV fractions augmented cellular protrusion formation in a
      CX3CL1/fractalkine-dependent fashion and enhanced the directional migratory
      response of human dendritic cells along guidance cues. We conclude that
      perilymphatic LEC exosomes enhance exploratory behavior and thus promote
      directional migration of CX3CR1-expressing cells in complex tissue environments.

PMID- 29650780
TI  - Differentiating Atypical Hemangiomas and Metastatic Vertebral Lesions: The Role
      of T1-Weighted Dynamic Contrast-Enhanced MRI.
AB  - BACKGROUND AND PURPOSE: Vertebral hemangiomas are benign vascular lesions that
      are almost always incidentally found in the spine. Their classic typical
      hyperintense appearance on T1- and T2-weighted MR images is diagnostic.
      Unfortunately, not all hemangiomas have the typical appearance, and they can
      mimic metastases on routine MR imaging. These are generally referred to as
      atypical hemangiomas and can result in misdiagnosis and ultimately additional
      imaging, biopsy, and unnecessary costs. Our objective was to assess the utility
      of dynamic contrast-enhanced MR imaging perfusion in distinguishing vertebral
      atypical hemangiomas and malignant vertebral metastases. We hypothesized that
      permeability and vascular density will be increased in metastases compared with
      atypical hemangiomas. MATERIALS AND METHODS: Consecutive patients from 2011 to
      2015 with confirmed diagnoses of atypical hemangiomas and spinal metastases from
      breast and lung carcinomas with available dynamic contrast-enhanced MR imaging
      were analyzed. Time-intensity curves were qualitatively compared among the
      groups. Perfusion parameters, plasma volume, and permeability constant were
      quantified using an extended Tofts 2-compartment pharmacokinetic model.
      Statistical significance was tested using the Mann-Whitney U test. RESULTS:
      Qualitative inspection of dynamic contrast-enhanced MR imaging time-intensity
      curves demonstrated differences in signal intensity and morphology between
      metastases and atypical hemangiomas. Quantitative analysis of plasma volume and
      permeability constant perfusion parameters showed significantly higher values in
      metastatic lesions compared with atypical hemangiomas (P < .001). CONCLUSIONS:
      Our data demonstrate that plasma volume and permeability constant perfusion
      parameters and qualitative inspection of contrast-enhancement curves can be used
      to differentiate atypical hemangiomas from vertebral metastatic lesions. This
      work highlights the benefits of adding perfusion maps to conventional sequences
      to improve diagnostic accuracy.

PMID- 29650781
TI  - Anatomic and Angiographic Analyses of Ophthalmic Artery Collaterals in Moyamoya
      Disease.
AB  - BACKGROUND AND PURPOSE: Moyamoya disease is a progressive neurovascular pathology
      defined by steno-occlusive disease of the distal internal carotid artery and
      associated with the development of compensatory vascular collaterals. The
      etiology and exact anatomy of vascular collaterals have not been extensively
      studied. The aim of this study was to describe the anatomy of collaterals
      developed between the ophthalmic artery and the anterior cerebral artery in a
      Moyamoya population. MATERIALS AND METHODS: All patients treated for Moyamoya
      disease from 2004 to 2016 in 4 neurosurgical centers with available cerebral
      digital subtraction angiography were included. Sixty-three cases were evaluated,
      and only 38 met the inclusion criteria. Two patients had a unilateral cervical
      internal carotid occlusion that limited analysis of ophthalmic artery collaterals
      to one hemisphere. This study is consequently based on the analysis of 74
      cerebral hemispheres. RESULTS: Thirty-eight patients fulfilled the inclusion
      criteria. The most frequently encountered anastomosis between the ophthalmic
      artery and cerebral artery was a branch of the anterior ethmoidal artery (31.1%,
      23 hemispheres). In case of proximal stenosis of the anterior cerebral artery, a
      collateral from the posterior ethmoidal artery could be visualized (16
      hemispheres, 21.6%). One case (1.4%) of anastomosis between the lacrimal artery
      and the middle meningeal artery that permitted the vascularization of a middle
      cerebral artery territory was also noted. CONCLUSIONS: Collaterals from the
      ophthalmic artery are frequent in Moyamoya disease. Their development depends on
      the perfusion needs of the anterior cerebral artery territories. Three other
      systems of compensation could be present (callosal circle, leptomeningeal
      anastomosis, and duro-pial anastomoses).

PMID- 29650782
TI  - Treatment of Distal Anterior Cerebral Artery Aneurysms with Flow-Diverter Stents:
      A Single-Center Experience.
AB  - BACKGROUND AND PURPOSE: Flow diversion for aneurysms beyond the circle of Willis
      is still debated. Our aim was to evaluate the safety and efficacy of flow
      diversion treatment of distal anterior cerebral artery aneurysms. MATERIALS AND
      METHODS: Consecutive patients with distal anterior cerebral artery aneurysms
      treated from January 2014 to October 2017 were evaluated retrospectively with
      prospectively maintained data. Treatment was performed only for unruptured or
      recanalized aneurysms after coiling. Technical feasibility, procedural
      complications, aneurysm occlusion (O'Kelly-Marotta grading scale), and clinical
      outcome were evaluated. RESULTS: Fifteen patients were included in the study,
      with 17 distal anterior cerebral artery saccular aneurysms treated with flow
      diverter stents. Mean aneurysm size was 4.25 +/- 3.9 mm; range, 2-9 mm. Flow
      diversion was used as retreatment among 6 previously coiled aneurysms (5 ruptured
      and coiled in the acute phase, and 1 unruptured and recanalized). Stent
      deployment was technically successful in all cases. During the perioperative
      period, 1 patient experienced a transient minor stroke (6%), whereas 2 patients
      reported acute in-stent thrombosis with disabling ischemic complications (13%).
      Fourteen patients and 16 aneurysms were available during a mean radiologic follow
      up of 12 months (range, 3-24 months). Overall, 12 (75%) aneurysms were completely
      occluded (O'Kelly-Marotta grading scale score D), 1 aneurysm (6%) showed near
      complete occlusion (O'Kelly-Marotta grading scale score C), and 3 aneurysms (19%)
      were incompletely occluded (O'Kelly-Marotta grading scale, score B). All 6
      aneurysms previously coiled were completely occluded after flow diversion,
      whereas 70% of aneurysms treated with flow diverters alone showed complete/near
      complete occlusion (O'Kelly-Marotta grading scale C-D). There were no cases of
      aneurysm rupture, in-stent occlusion, or retreatment during long-term follow-up.
      CONCLUSIONS: Treatment of distal anterior cerebral artery aneurysms with flow
      diverter stents is feasible and effective, with high rates of aneurysm occlusion.
      Flow diversion plus coiling, in the retreatment of lesions previously coiled,
      allowed higher rates of occlusion compared with flow diverters alone. However,
      the risk of ischemic complications is not negligible, and flow-diversion
      treatment should be evaluated only for aneurysms not amenable to simple coil
      embolization.

PMID- 29650783
TI  - Percutaneous CT-Guided Biopsies of the Cervical Spine: Technique, Histopathologic
      and Microbiologic Yield, and Safety at a Single Academic Institution.
AB  - BACKGROUND AND PURPOSE: Cervical spine biopsies can be challenging due to the
      anatomy and the adjacent critical structures. Percutaneous image-guided biopsies
      can obviate the need for an open biopsy, however there have been few studies
      looking at the approaches, safety, and efficacy of percutaneous cervical spine
      biopsies. This retrospective study evaluated technical considerations,
      histopathologic and microbiologic yield, and safety in CT-guided cervical bone
      biopsies. MATERIALS AND METHODS: A retrospective review of cervical bone and/or
      bone/disc biopsies performed from January 2010 to January 2017 was included in
      this study. Clinical diagnosis and indication, patient demographics, biopsy
      location, biopsy needle type, technical approach, lesion size, dose-length
      product, conscious sedation details, complications, and diagnostic
      histopathologic and/or microbiologic yield were recorded for each case and
      summarized. RESULTS: A total of 73 patients underwent CT-guided cervical bone
      biopsies. Fifty-three percent (39/73) were for clinical/imaging concern for
      infection and 47% (34/73) were for primary tumors or metastatic disease. Thirty
      four percent (25/73) were of the inferior cervical spine (ie, C6 and C7). A
      sufficient sample was obtained for histopathologic and microbiologic analyses in
      96% (70/73) of the biopsies. Forty-six percent (18/39) of those samples taken for
      infection had positive cultures. Two intraprocedural complications occurred in
      which the patients became hypotensive during the procedure without long-term
      complications. CONCLUSIONS: Percutaneous CT-guided biopsy of the cervical spine
      is an effective and safe procedure with high diagnostic yield and can obviate
      open procedures for histopathologic and microbiologic analyses of patients with
      clinical and imaging findings concerning for infection or primary and metastatic
      osseous lesions.

PMID- 29650784
TI  - Under Pressure: Comparison of Aspiration Techniques for Endovascular Mechanical
      Thrombectomy.
AB  - BACKGROUND AND PURPOSE: Blood flow should be interrupted during mechanical
      thrombectomy to prevent embolization of clot fragments. The purpose of our study
      was to provide a handy overview of the most common aspiration devices and to
      quantify their flow characteristics. MATERIALS AND METHODS: We assessed
      volumetric flow rates generated by a 60-mL VacLok vacuum pressure syringe, a Pump
      MAX aspiration pump, and a Dominant Flex suction pump connected to the following:
      1) an 8F long sheath, 2) an 8F balloon-guide catheter, 3) an ACE 64 distal
      aspiration catheter, and 4) an AXS Catalyst 6 Distal Access Catheter. We used a
      water/glycerol solution, which was kept at a constant temperature of 20 degrees C
      (viscosity, 3.7 mPa . s). RESULTS: Aspiration with the syringe and the Dominant
      Flex suction pump achieved the highest flows, whereas aspiration with the Pump
      MAX was significantly lower (P < .001). Resistors in the aspiration system
      (tubing, connectors, and so forth) restricted flows, especially when the
      resistance of the catheter was small (due to its large diameter) and the
      connected resistors became the predominant resistance (P < .001). The syringe
      achieved an average vacuum pressure of -90 kPa, and the resulting flow was
      constant during almost the entire procedure of filling the syringe. CONCLUSIONS:
      Sixty-milliliter VacLok vacuum pressure syringes and the Dominant Flex suction
      pump achieved high and constant flows likely sufficient to reverse blood flow
      during thrombectomy with an 8F sheath or balloon-guide catheter in the ICA and
      modern distal aspiration catheters in the MCA. The Pump MAX aspiration pump is
      dedicated for use with distal aspiration catheters and is unlikely to reverse
      blood flow in the ICA and MCA without balloon protection.

PMID- 29650785
TI  - Surpass Streamline Flow-Diverter Embolization Device for Treatment of Iatrogenic
      and Traumatic Internal Carotid Artery Injuries.
AB  - Iatrogenic and traumatic cerebral internal carotid artery injuries are uncommon
      but potentially lethal complications. Direct surgical repair of ICA injuries may
      be difficult in an acute setting. However, endovascular treatment with a flow
      diverter embolization device is a feasible alternative technique that we
      experienced. In this clinical report, we describe demographic data, radiographic
      images, lesion characteristics, endovascular procedure notes, postprocedural
      hospital course, and follow-up digital subtraction angiography of 5 patients. At
      least 6-month follow-up was available in all patients without occurrence of
      rebleeding and other complications.

PMID- 29650786
TI  - Association of Quantified Location-Specific Blood Volumes with Delayed Cerebral
      Ischemia after Aneurysmal Subarachnoid Hemorrhage.
AB  - BACKGROUND AND PURPOSE: Delayed cerebral ischemia is a severe complication of
      aneurysmal SAH and is associated with a high case morbidity and fatality. The
      total blood volume and the presence of intraventricular blood on CT after
      aneurysmal SAH are associated with delayed cerebral ischemia. Whether quantified
      location-specific (cisternal, intraventricular, parenchymal, and subdural) blood
      volumes are associated with delayed cerebral ischemia has been infrequently
      researched. This study aimed to associate quantified location-specific blood
      volumes with delayed cerebral ischemia. MATERIALS AND METHODS: Clinical and
      radiologic data were collected retrospectively from consecutive patients with
      aneurysmal SAH with available CT scans within 24 hours after ictus admitted to 2
      academic centers between January 2009 and December 2011. Total blood volume was
      quantified using an automatic hemorrhage-segmentation algorithm. Segmented blood
      was manually classified as cisternal, intraventricular, intraparenchymal, or
      subdural. Adjusted ORs with 95% confidence intervals for delayed cerebral
      ischemia per milliliter of location-specific blood were calculated using
      multivariable logistic regression analysis. RESULTS: We included 282 patients.
      Per milliliter increase in blood volume, the adjusted OR for delayed cerebral
      ischemia was 1.02 (95% CI, 1.01-1.04) for cisternal, 1.02 (95% CI, 1.00-1.04) for
      intraventricular, 0.99 (95% CI, 0.97-1.02) for intraparenchymal, and 0.96 (95%
      CI, 0.86-1.07) for subdural blood. CONCLUSIONS: Our findings suggest that in
      patients with aneurysmal subarachnoid hemorrhage, the cisternal blood volume has
      a stronger relation with delayed cerebral ischemia than the blood volumes at
      other locations in the brain.

PMID- 29650787
TI  - Management of Small Unruptured Intracranial Aneurysms: A Survey of
      Neuroradiologists.
AB  - BACKGROUND AND PURPOSE: The long-term history and management of unruptured
      intracranial aneurysms is not well understood. Our aim was to determine current
      practice patterns in the management of unruptured intracranial aneurysms,
      especially regarding imaging surveillance for conservatively managed aneurysms of
      this type. MATERIALS AND METHODS: An on-line survey was designed to examine
      physician practice and preference regarding the management of small unruptured
      intracranial aneurysms (<=7 mm in diameter). The survey was circulated to members
      of the American Society of Neuroradiology. Participation was voluntary, and all
      responses were anonymous. RESULTS: A total of 227 individual survey responses
      were obtained and included in the analysis with 54.6% (124/227) from diagnostic
      neuroradiologists (practicing >50% neuroradiology) and one-third (29%) from
      neurointerventional radiologists. One hundred seventy-three of 227 responded that
      routine, periodic imaging surveillance would be appropriate for conservatively
      managed unruptured intracranial aneurysms, and 84% of respondents recommended
      surveillance frequency of at least once a year. Fifty-nine percent favored
      indefinite, life-long follow-up for small unruptured intracranial aneurysms, and
      a similar number of respondents favored noncontrast MR angiography for aneurysm
      follow-up. Significant heterogeneity was found in size measurements used to
      assess aneurysms and criteria used to define growth on surveillance imaging.
      CONCLUSIONS: The natural history of intracranial aneurysms is not well
      understood. A large proportion of incidentally detected, unruptured aneurysms are
      small (<7 mm). The survey results show significant heterogeneity in practice even
      among neuroradiologists and underlies the need to standardize imaging practice.
      Further studies are needed to assess the optimal frequency and duration of
      surveillance imaging for unruptured intracranial aneurysms. The criteria used to
      measure aneurysms and define growth on imaging also need to be standardized.

PMID- 29650788
TI  - Serum Exosomal Long Noncoding RNAs ENSG00000258332.1 and LINC00635 for the
      Diagnosis and Prognosis of Hepatocellular Carcinoma.
AB  - Background: Increasing studies suggest that long noncoding RNAs (lncRNAs) are
      involved in carcinogenesis of human cancers and might be used as diagnostic
      biomarkers for cancers.Methods: A total of 301 participants were recruited in the
      first part of the study, including a hepatocellular carcinoma (HCC) group (n =
      60), liver cirrhosis (LC) group (n = 85), chronic hepatitis B (CHB) group (n =
      96), and healthy subjects (n = 60). In the second part, we collected 55 HCC
      patients, 60 CHB patients, and 60 healthy subjects as an independent cohort to
      validate the ability of the experiential lncRNAs for identifying HCC from CHB. A
      commercial kit was used to isolate serum exosomes and total RNA. The relative
      levels of lnRNAs and GAPDH mRNA were measured with TaqMan PCR.Results: The
      results showed that the levels of ENSG00000258332.1 and LINC00635 in the HCC
      group were significantly higher than those in the other groups (all P < 0.05). A
      high ENSG00000258332.1 level in HCC was associated with portal vein tumor emboli,
      lymph node metastasis, TNM stage, and overall survival (OS; all P < 0.05), and a
      high LINC00635 level was related to lymph node metastasis, TNM stage, and OS (all
      P < 0.05). ENSG00000258332.1 discriminated HCC from CHB, gaining an area under
      the ROC curve (AUC) of 0.719 (cutoff value of 1.345); LINC00635 gained an AUC of
      0.750 (cutoff value of 1.690). Furthermore, the AUC for the combination of the 2
      lncRNAs and serum AFP (cutoff value of 20 MUg/L) was 0.894. The abilities of the
      2 lncRNAs for identifying HCC from CHB were validated by an independent
      cohort.Conclusions: The results suggested that the combination of serum exosomal
      ENSG00000258332.1, LINC00635, and AFP may be a valuable assay in diagnosis and
      prognosis of HCC.Impact: Our data will shed light on exosomal lncRNAs as
      biomarkers for HCC. Cancer Epidemiol Biomarkers Prev; 27(6); 710-6. (c)2018 AACR.

PMID- 29650789
TI  - Reparameterization of PAM50 Expression Identifies Novel Breast Tumor Dimensions
      and Leads to Discovery of a Genome-Wide Significant Breast Cancer Locus at 12q15.
AB  - Background: Breast tumor subtyping has failed to provide impact in susceptibility
      genetics. The PAM50 assay categorizes breast tumors into: Luminal A, Luminal B,
      HER2-enriched and Basal-like. However, tumors are often more complex than simple
      categorization can describe. The identification of heritable tumor
      characteristics has potential to decrease heterogeneity and increase power for
      gene finding.Methods: We used 911 sporadic breast tumors with PAM50 expression
      data to derive tumor dimensions using principal components (PC). Dimensions in
      238 tumors from high-risk pedigrees were compared with the sporadic tumors. Proof
      of-concept gene mapping, informed by tumor dimension, was performed using Shared
      Genomic Segment (SGS) analysis.Results: Five dimensions (PC1-5) explained the
      majority of the PAM50 expression variance: three captured intrinsic subtype, two
      were novel (PC3, PC5). All five replicated in 745 TCGA tumors. Both novel
      dimensions were significantly enriched in the high-risk pedigrees (intrinsic
      subtypes were not). SGS gene-mapping in a pedigree identified a 0.5 Mb genome
      wide significant region at 12q15 This region segregated through 32 meioses to 8
      breast cancer cases with extreme PC3 tumors (P = 2.6 * 10-8).Conclusions: PC
      analysis of PAM50 gene expression revealed multiple independent, quantitative
      measures of tumor diversity. These tumor dimensions show evidence for
      heritability and potential as powerful traits for gene mapping.Impact: Our study
      suggests a new approach to describe tumor expression diversity, provides new
      avenues for germline studies, and proposes a new breast cancer locus. Similar
      reparameterization of expression patterns may inform other studies attempting to
      model the effects of tumor heterogeneity. Cancer Epidemiol Biomarkers Prev;
      27(6); 644-52. (c)2018 AACR.

PMID- 29650790
TI  - Effect of Endocannabinoid Oleamide on Rat and Human Liver Cytochrome P450 Enzymes
      in In Vitro and In Vivo Models.
AB  - The endocannabinoid system is important for many physiologic and pathologic
      processes, but its role in the regulation of liver cytochromes P450 (P450s)
      remains unknown. We studied the influence of the endocannabinoid oleamide on rat
      and human liver P450s. Oleamide was administered intraperitoneally to rats at
      doses of 0.1, 1, and 10 mg/kg per day for 7 days. The content and activity of key
      P450s were evaluated in rat liver microsomes. Moreover, interactions with nuclear
      receptors regulating P450 genes and serum levels of their ligands (prolactin,
      corticosterone, and free triiodothyronine) were tested in in vitro P450
      inhibition assays. Decreased protein levels and metabolic activities of CYP1A2,
      CYP2B, and CYP2C11, along with a drop in metabolic activity of CYP2D2, were
      observed in animals treated with oleamide (10 mg/kg per day). The activities of
      CYP2C6, CYP2A, and CYP3A and the levels of hormones were not altered. In vitro,
      oleamide exhibited a weak inhibition of rat CYP1A2, CYP2D2, and CYP2C6. The
      activities of rat CYP2A, CYP2B, CYP2C11, and CYP3A and human CYP1A2, CYP2B6,
      CYP2C9, and CYP3A4 were not altered. Oleamide did not interact with human
      pregnane X, constitutive androstane, or aryl hydrocarbon receptors in reporter
      gene experiments and did not regulate their target P450 genes in primary human
      hepatocytes. Our results indicate that oleamide caused the downregulation of some
      rat liver P450s, and hormones are not mediators of this effect. In vitro oleamide
      inhibits mainly rat CYP2C6 and is neither an agonist nor antagonist of major
      human nuclear receptors involved in the regulation of xenobiotic metabolism.

PMID- 29650791
TI  - Impairments in Adipose Tissue Microcirculation in Type 2 Diabetes Mellitus
      Assessed by Real-Time Contrast-Enhanced Ultrasound.
AB  - BACKGROUND: In obesity and type 2 diabetes mellitus (T2D), adipose tissue
      expansion (because of larger adipocytes) results in reduced microvascular density
      which is thought to lead to adipocyte hypoxia, inflammation, and reduced nutrient
      delivery to the adipocyte. Adipose tissue microvascular responses in humans with
      T2D have not been extensively characterized. Furthermore, it has not been
      determined whether impaired microvascular responses in human adipose tissue are
      most closely associated with adiposity, inflammation, or altered metabolism.
      METHODS AND RESULTS: Overnight-fasted healthy controls (n=24, 9 females/15 males)
      and people with T2D (n=21, 8 females/13 males) underwent a body composition scan
      (dual-energy X-ray absorptiometry), an oral glucose challenge (50 g glucose) and
      blood analysis of clinical chemistries and inflammatory markers. Abdominal
      subcutaneous adipose tissue microvascular responses were measured by contrast
      enhanced ultrasound at baseline and 1-hour post-oral glucose challenge. Adipose
      tissue microvascular blood volume was significantly elevated in healthy subjects
      1-hour post-oral glucose challenge; however, this effect was absent in T2D.
      Adipose tissue microvascular blood flow was lower in people with T2D at baseline
      and was significantly blunted post-oral glucose challenge compared with controls.
      Adipose tissue microvascular blood flow was negatively associated with truncal
      fat (%), glucoregulatory function, fasting triglyceride and nonesterified fatty
      acid levels, and positively associated with insulin sensitivity. Truncal fat (%),
      systolic blood pressure, and insulin sensitivity were the only correlates with
      microvascular blood volume. Systemic inflammation was not associated with adipose
      tissue microvascular responses. CONCLUSIONS: Impaired microvascular function in
      adipose tissue during T2D is not conditionally linked to systemic inflammation
      but is associated with other characteristics of the metabolic syndrome (obesity,
      insulin resistance, hyperglycemia, and dyslipidemia).

PMID- 29650792
TI  - Three-Dimensional Transesophageal Echocardiography Reconstruction in Removal of a
      7-cm Left Atrial Thrombus Attached to a Displaced Amplatzer Device.

PMID- 29650793
TI  - Cause or Effect? Microvascular Dysfunction in Insulin-Resistant States.

PMID- 29650795
TI  - How much of the missing heritability of ALS is hidden in known ALS genes?

PMID- 29650796
TI  - Heartbeat: Reporting guidelines for high quality clinical cardiology research.

PMID- 29650794
TI  - Comprehensive analysis of the mutation spectrum in 301 German ALS families.
AB  - OBJECTIVES: Recent advances in amyotrophic lateral sclerosis (ALS) genetics have
      revealed that mutations in any of more than 25 genes can cause ALS, mostly as an
      autosomal-dominant Mendelian trait. Detailed knowledge about the genetic
      architecture of ALS in a specific population will be important for genetic
      counselling but also for genotype-specific therapeutic interventions. METHODS:
      Here we combined fragment length analysis, repeat-primed PCR, Southern blotting,
      Sanger sequencing and whole exome sequencing to obtain a comprehensive profile of
      genetic variants in ALS disease genes in 301 German pedigrees with familial ALS.
      We report C9orf72 mutations as well as variants in consensus splice sites and non
      synonymous variants in protein-coding regions of ALS genes. We furthermore
      estimate their pathogenicity by taking into account type and frequency of the
      respective variant as well as segregation within the families. RESULTS: 49% of
      our German ALS families carried a likely pathogenic variant in at least one of
      the earlier identified ALS genes. In 45% of the ALS families, likely pathogenic
      variants were detected in C9orf72, SOD1, FUS, TARDBP or TBK1, whereas the
      relative contribution of the other ALS genes in this familial ALS cohort was 4%.
      We identified several previously unreported rare variants and demonstrated the
      absence of likely pathogenic variants in some of the recently described ALS
      disease genes. CONCLUSIONS: We here present a comprehensive genetic
      characterisation of German familial ALS. The present findings are of importance
      for genetic counselling in clinical practice, for molecular research and for the
      design of diagnostic gene panels or genotype-specific therapeutic interventions
      in Europe.

PMID- 29650797
TI  - Response: Complex issue of lipoprotein functions in rheumatoid arthritis.

PMID- 29650798
TI  - Role of nitric oxide in vasovagal syncope. A puzzle solved but there could be
      another piece.

PMID- 29650799
TI  - Pervasive mutations of JAK-STAT pathway genes in classical Hodgkin lymphoma.
AB  - Dissecting the pathogenesis of classical Hodgkin lymphoma (cHL), a common cancer
      in young adults, remains challenging because of the rarity of tumor cells in
      involved tissues (usually <5%). Here, we analyzed the coding genome of cHL by
      microdissecting tumor and normal cells from 34 patient biopsies for a total of
      ~50 000 singly isolated lymphoma cells. We uncovered several recurrently mutated
      genes, namely, STAT6 (32% of cases), GNA13 (24%), XPO1 (18%), and ITPKB (16%),
      and document the functional role of mutant STAT6 in sustaining tumor cell
      viability. Mutations of STAT6 genetically and functionally cooperated with
      disruption of SOCS1, a JAK-STAT pathway inhibitor, to promote cHL growth.
      Overall, 87% of cases showed dysregulation of the JAK-STAT pathway by genetic
      alterations in multiple genes (also including STAT3, STAT5B, JAK1, JAK2, and
      PTPN1), attesting to the pivotal role of this pathway in cHL pathogenesis and
      highlighting its potential as a new therapeutic target in this disease.

PMID- 29650801
TI  - The role of JAK2 inhibitors in MPNs 7 years after approval.
AB  - Myeloproliferative neoplasms (MPNs) include essential thrombocythemia,
      polycythemia vera (PV), and primary myelofibrosis (MF). Phenotype-driver
      mutations of JAK2, CALR, and MPL genes are present in MPNs and can be variably
      combined with additional mutations. Driver mutations entail a constitutive
      activation of the JAK2/STAT pathway, the key signaling cascade in MPNs. Among
      JAK2 inhibitors (JAKis), ruxolitinib (RUX) has been approved for the treatment of
      intermediate and high-risk MF and for PV inadequately controlled by or intolerant
      of hydroxyurea. Other JAKis, such as fedratinib and pacritinib, proved to be
      useful in MF. The primary end points in MF trials were spleen volume response
      (SVR) and symptom response, whereas in PV trials they were hematocrit control
      with or without spleen response. In advanced MF, RUX achieved a long lasting SVR
      of >35% in ~60% of patients, establishing a new benchmark for MF treatment. RUX
      efficacy in early MF is also remarkable and toxicity is mild. In PV, RUX achieved
      hematocrit control in ~60% of cases and SVR in 40%. Symptom relief was evident in
      both conditions. In the long-term, however, many MF patients lose their SVR.
      Indeed, the definition of RUX failure and the design of new trials in this
      setting are unmet needs. Decrease of hemoglobin/platelet levels and increased
      infection rates are the most common side effects of RUX, and nonmelanoma skin
      tumors need to be monitored while on treatment. In conclusion, the introduction
      of JAKis raises the bar of treatment goals in MF and PV.

PMID- 29650800
TI  - MGUS, lymphoplasmacytic malignancies, and Gaucher disease: the significance of
      the clinical association.

PMID- 29650802
TI  - Variations and delays in COPD care warrant new targets, says college.

PMID- 29650803
TI  - Cost-effectiveness of Continuous Glucose Monitoring for Adults With Type 1
      Diabetes Compared With Self-Monitoring of Blood Glucose: The DIAMOND Randomized
      Trial.
AB  - OBJECTIVE: This study evaluated the societal cost-effectiveness of continuous
      glucose monitoring (CGM) in patients with type 1 diabetes (T1D) using multiple
      insulin injections. RESEARCH DESIGN AND METHODS: In the Multiple Daily Injections
      and Continuous Glucose Monitoring in Diabetes (DIAMOND) trial, 158 patients with
      T1D and HbA1c >=7.5% were randomized in a 2:1 ratio to CGM or control.
      Participants were surveyed at baseline and 6 months. Within-trial and lifetime
      cost-effectiveness analyses were conducted. A modified Sheffield T1D policy model
      was used to simulate T1D complications. The main outcome was cost per quality
      adjusted life-year (QALY) gained. RESULTS: Within the 6-month trial, the CGM
      group had similar QALYs to the control group (0.462 +/- 0.05 vs. 0.455 +/- 0.06
      years, P = 0.61). The total 6-month costs were $11,032 (CGM) vs. $7,236
      (control). The CGM group experienced reductions in HbA1c (0.60 +/- 0.74%
      difference in difference [DiD]), P < 0.01), the daily rate of nonsevere
      hypoglycemia events (0.07 DiD, P = 0.013), and daily test strip use (0.55 +/- 1.5
      DiD, P = 0.04) compared with the control group. In the lifetime analysis, CGM was
      projected to reduce the risk of T1D complications and increase QALYs by 0.54. The
      incremental cost-effectiveness ratio (ICER) was $98,108 per QALY for the overall
      population. By extending sensor use from 7 to 10 days in a real-world scenario,
      the ICER was reduced to $33,459 per QALY. CONCLUSIONS: For adults with T1D using
      multiple insulin injections and still experiencing suboptimal glycemic control,
      CGM is cost-effective at the willingness-to-pay threshold of $100,000 per QALY,
      with improved glucose control and reductions in nonsevere hypoglycemia.

PMID- 29650804
TI  - Exploring Variation in Glycemic Control Across and Within Eight High-Income
      Countries: A Cross-sectional Analysis of 64,666 Children and Adolescents With
      Type 1 Diabetes.
AB  - OBJECTIVE: International studies on childhood type 1 diabetes (T1D) have focused
      on whole-country mean HbA1c levels, thereby concealing potential variations
      within countries. We aimed to explore the variations in HbA1c across and within
      eight high-income countries to best inform international benchmarking and policy
      recommendations. RESEARCH DESIGN AND METHODS: Data were collected between 2013
      and 2014 from 64,666 children with T1D who were <18 years of age across 528
      centers in Germany, Austria, England, Wales, U.S., Sweden, Denmark, and Norway.
      We used fixed- and random-effects models adjusted for age, sex, diabetes
      duration, and minority status to describe differences between center means and to
      calculate the proportion of total variation in HbA1c levels that is attributable
      to between-center differences (intraclass correlation [ICC]). We also explored
      the association between within-center variation and children's glycemic control.
      RESULTS: Sweden had the lowest mean HbA1c (59 mmol/mol [7.6%]) and together with
      Norway and Denmark showed the lowest between-center variations (ICC <=4%).
      Germany and Austria had the next lowest mean HbA1c (61-62 mmol/mol [7.7-7.8%])
      but showed the largest center variations (ICC ~15%). Centers in England, Wales,
      and the U.S. showed low-to-moderate variation around high mean values. In pooled
      analysis, differences between counties remained significant after adjustment for
      children characteristics and center effects (P value <0.001). Across all
      countries, children attending centers with more variable glycemic results had
      higher HbA1c levels (5.6 mmol/mol [0.5%] per 5 mmol/mol [0.5%] increase in center
      SD of HbA1c values of all children attending a specific center). CONCLUSIONS: At
      similar average levels of HbA1c, countries display different levels of center
      variation. The distribution of glycemic achievement within countries should be
      considered in developing informed policies that drive quality improvement.

PMID- 29650806
TI  - Timing and Location of Emergency Department Revisits.
AB  - BACKGROUND: Emergency department (ED) revisits are used as a measure of care
      quality. Many EDs measure only revisits to the same facility, underestimating
      true rates. We sought to determine the frequency, location, and predictors of ED
      revisits to the same or a different ED. METHODS: We studied ED discharges for
      children <18 years old in Maryland and New York in the statewide ED and inpatient
      databases. Revisits were defined as ED visits within 7 days of an index visit.
      Our primary outcome was the proportion of revisits that were different-hospital
      revisits (DHRs). We measured the underestimation of total revisits when only same
      hospital revisits were measured. We determined the risk of DHR by quartile of
      annual ED pediatric volume, adjusting for case mix, insurance, state, and urban
      location. RESULTS: Revisits across 261 EDs occurred after 5.9% of 4.3 million
      discharges. A per-ED median 21.9% of revisits were DHRs (interquartile range
      14.2%-34.6%). Measuring only same-hospital revisits underestimated total revisits
      by 17.4%. The proportions of revisits that were DHRs by increasing volume
      quartile were 28.1%, 25.5%, 22.6%, and 14.5%. The adjusted risk of DHR was lower
      for increasing quartiles of pediatric volume (adjusted odds ratio for highest
      versus lowest quartile 0.27; 95% confidence interval, 0.19-0.36). CONCLUSIONS:
      Measuring ED revisits only at the index ED significantly underestimates total
      revisits. Lower pediatric volume is associated with higher DHRs as a proportion
      of revisits. When using revisits as a measure of emergency care quality, effort
      should be made to assess revisits to different EDs.

PMID- 29650807
TI  - Perceptions of Health Care Transition Care Coordination in Patients With Chronic
      Illness.
AB  - OBJECTIVES: Expert consensus jointly authored in 2011 by the American Academy of
      Pediatrics, American Academy of Family Physicians, and American College of
      Physicians supports the use of health care transition (HCT) care coordination
      (CC). Although gaps in care are addressed in these practice-based implementation
      recommendations, such recommendations have never undergone rigorous assessment.
      We assessed the effectiveness of implementation on quality of chronic illness
      care and CC during HCT for adolescents and young adults. METHODS: Adolescents and
      young adults with special health care needs were enrolled in a randomized HCT CC
      intervention. Intervention participants received HCT CC as outlined in the 2011
      clinical report. Perceptions of chronic illness care quality and CC were assessed
      at 0, 6, and 12 months. RESULTS: Intervention participants had a Patient
      Assessment of Chronic Illness Care score at 12 months of 3.6 vs 3.3 compared with
      participants in the control group (P = .01). Intervention participants had higher
      average scores for patient activation (3.7 vs 3.4; P = .01), problem solving (3.8
      vs 3.4; P = .02), and coordination/follow-up (3.0 vs 2.5; P < .01). The Client
      Perceptions of Coordination Questionnaire revealed that intervention participants
      had 2.5 times increased odds to endorse mostly or always receiving the services
      they thought they needed and had 2.4 times increased odds to have talked to their
      provider about future care (P < .01). CONCLUSIONS: Implementing recommended HCT
      CC practices improved patient or patient caregiver perception of quality of
      chronic illness care and CC especially among the most complex patients.

PMID- 29650805
TI  - Co-targeting BET and MEK as salvage therapy for MAPK and checkpoint inhibitor
      resistant melanoma.
AB  - Despite novel therapies for melanoma, drug resistance remains a significant
      hurdle to achieving optimal responses. NRAS-mutant melanoma is an archetype of
      therapeutic challenges in the field, which we used to test drug combinations to
      avert drug resistance. We show that BET proteins are overexpressed in NRAS-mutant
      melanoma and that high levels of the BET family member BRD4 are associated with
      poor patient survival. Combining BET and MEK inhibitors synergistically curbed
      the growth of NRAS-mutant melanoma and prolonged the survival of mice bearing
      tumors refractory to MAPK inhibitors and immunotherapy. Transcriptomic and
      proteomic analysis revealed that combining BET and MEK inhibitors mitigates a
      MAPK and checkpoint inhibitor resistance transcriptional signature, downregulates
      the transcription factor TCF19, and induces apoptosis. Our studies demonstrate
      that co-targeting MEK and BET can offset therapy resistance, offering a salvage
      strategy for melanomas with no other therapeutic options, and possibly other
      treatment-resistant tumor types.

PMID- 29650808
TI  - Correction: Adverse pregnancy outcomes in women exposed to gabapentin and
      pregabalin: data from a population-based study.

PMID- 29650809
TI  - [Molecular Targeted Therapies for Hereditary Cancer Syndrome].
AB  - Development of molecular targeted drugs has achieved remarkable improvement of
      systemic cancer therapy. Recently, the several molecular targeted drugs have
      become available which associated with the status of responsible genes for
      hereditary cancer syndrome. These drugs would allow to establish specific
      strategy for hereditary cancer syndrome or sporadic cancers with similar
      biological phenotype with hereditary cancer. Genetic tests for the diagnosis of
      hereditary cancer syndrome will have the meaning of biomarker for predicting the
      efficacy of these molecular targeted drugs. This review summarized the molecular
      targeted drugs including immune checkpoint inhibitors with potential effects for
      hereditary cancer syndrome, such as anti-PD-1 antibody for Lynch syndrome, PARP
      inhibitor for hereditary breast and ovarian cancer syndrome, multi-kinase
      inhibitor for multiple endocrine neoplasia type 2.

PMID- 29650810
TI  - [Artificial Intelligence in Drug Discovery].
AB  - According to the increase of data generated from analytical instruments,
      application of artificial intelligence(AI)technology in medical field is
      indispensable. In particular, practical application of AI technology is strongly
      required in "genomic medicine" and "genomic drug discovery" that conduct medical
      practice and novel drug development based on individual genomic information. In
      our laboratory, we have been developing a database to integrate genome data and
      clinical information obtained by clinical genome analysis and a computational
      support system for clinical interpretation of variants using AI. In addition,
      with the aim of creating new therapeutic targets in genomic drug discovery, we
      have been also working on the development of a binding affinity prediction system
      for mutated proteins and drugs by molecular dynamics simulation using
      supercomputer "Kei". We also have tackled for problems in a drug virtual
      screening. Our developed AI technology has successfully generated virtual
      compound library, and deep learning method has enabled us to predict interaction
      between compound and target protein.

PMID- 29650811
TI  - [Human Genome Data and Drug Development].
AB  - Human genome data has been of growing importance in drug development, which we
      call "genome-based drug development", and medical big data including genome and
      clinical data is becoming indispensable resource. In this paper, we reviewed(
      1)drug development utilizing genome data,(2)current situation of development of
      platform for genomic medicine collecting genome and clinical data, and(3)new
      movement of genomic data sharing.

PMID- 29650812
TI  - [Clinical Implementation of Precision Medicine].
AB  - In the end of last year, the US Food and Drug Administration has announced the
      authorization of MSK-IMPACT(TM), clinical test based on multiplex cancer panel
      profiling for genetic mutations and other alterations in patients' tumors, while
      in Japan, NCC Oncopanel, domestic multiplex cancer panel, is scheduled to be
      clinically implemented as advanced medical care B in this coming spring, chasing
      the state of the art technology for cancer treatment. In this article, we outline
      a recently published roadmap for precision medicine in Japan, together with our
      years of experience on cancer diagnosis and treatment based on multiplex cancer
      panel at Okayama University Hospital and Okadai Biobank.

PMID- 29650813
TI  - [The Cutting Edge of Sarcoma Genomics].
AB  - Sarcoma is well-known rare cancer with few therapeutic options. Recent
      comprehensive genomic analyses of adult soft tissue sarcoma revealed few somatic
      mutations and massive copy number variations(CNVs)by the specific chromosomes.
      Those features are quite different from the genomics of carcinoma such as lung
      and colon cancers in which driver and passenger mutations play a central role in
      the pathogenesis. Furthermore, it has been demonstrated that substantial
      population of sarcoma patients has pathological germline variants of cancer
      predisposition genes. These findings imply that, in addition to somatic
      mutations, inherited germline variants may play a role in the disease state of
      sarcoma via dosage effects. On this basis, we also discuss on the prospect and
      limitation of the precision medicine of sarcoma.

PMID- 29650814
TI  - [Melanoma and Non-Melanoma Skin Cancers].

PMID- 29650815
TI  - [I. New Treatment of Metastatic Melanoma].

PMID- 29650816
TI  - [II. Diagnosis and Treatment for Nail Apparatus(Subungual)Melanoma].

PMID- 29650817
TI  - [III. Diagnosis and Management of Keratoacanthoma].

PMID- 29650818
TI  - [Combinatorial Use of Rapid-Onset Opioid and Short-Acting Opioid Is Effective
      against Breakthrough Cancer Pain].
AB  - Breakthrough cancer pain is divided into "predictable breakthrough pain" and
      "unpredictable breakthrough pain". Uncontrolled breakthrough pain in cancer
      negatively affects the quality of life of the patients. The short-acting
      opioid(SAO) requires considerable time to produce analgesia, and is not adequate
      as a rescue drug. The rapid-onset opioid(ROO)immediately produces analgesia, but
      its appropriate usage is difficult. For instance, the frequency and interval of
      ROO usage is limited, making the optimization of dosage cumbersome. Therefore,
      ROO has not yet gained popularity. Here, we report that a combinatorial use of
      ROO and SAO is effective against breakthrough cancer pain, with SAO and ROO being
      suitable for "predictable breakthrough pain", and "unpredictable breakthrough
      pain", respectively. The effectiveness and safety of this combination were
      assessed for many patients with breakthrough cancer pain.

PMID- 29650819
TI  - [A Case Report of Neuroendocrine Carcinoma in the Gall Bladder Showing Recurrence
      Shortly after Surgery].
AB  - A55 -year-old woman with a 10*8mm protuberant gallbladder lesion visited our
      hospital. To determine possible malignancy, she underwent laparoscopic excision
      biopsy of the gallbladder, and pathological findings revealed an endocrine
      carcinoma in the gallbladder. Surgery involved extrahepatic bile duct resection,
      gallbladder bed resection, and hepatic portal lymph node resection. Recurrence in
      the peritoneal lymph node was observed in the early postoperative period.
      Chemotherapy was initiated with cisplatin and irinotecan, and continues 18 months
      post-operatively. Neuroendocrine carcinoma of the gallbladder is rare and is
      known to have a poor prognosis, with few confirmed treatments reported for this
      disease due to its rarity. Therefore, we report this case along with a review of
      the literature.

PMID- 29650820
TI  - [Rectal Mucinous Cancer with Submucosal Tumor-Like Morphology Preoperatively
      Diagnosed Using EUS-FNAB - A Case Report].
AB  - A man in his 70s presented with a chiefcomplaint ofbleeding during bowel
      movements. Subsequent colonoscopy revealed a submucosal tumor-like elevated
      lesion ofapproximately 4 cm situated in the sigmoid section ofthe rectum. EUS
      FNAB was performed, and the lesion was identified as mucinous cancer. Based on a
      diagnosis of rectal cancer(cT4a, cN0, cM0, cStage II), a low anterior resection
      was performed. Histopathological analysis of the resected specimen revealed a
      well-differentiated mucinous cancer. The tumor had ruptured the proper muscular
      layer and was developing in a submucosal tumor-like manner, protruding from the
      wall within a fibrous capsule. In Japan, only 15 cases of submucosal tumor-like
      colorectal mucinous cancer have been reported to date. It is rare for such cases
      to be preoperatively diagnosed as mucinous cancer using EUS-FNAB and then to
      undergo radical resection.

PMID- 29650821
TI  - [Continuation of Axitinib for Advanced Renal Cell Carcinoma by The Application of
      Homecare Urology - A Case Report and Literature Review].
AB  - A 56-year-old man with advanced RCC and a past medical history of type 2 diabetes
      underwent a radical left nephrectomy following a histological diagnosis of
      papillary RCC, G2, INF b, pT3, V1 in 1999. In 2008, sorafenib was started to
      treat multiple pulmonary metastases of RCC. In 2011, sorafenib was switched to
      sunitinib when radiologic progression was observed. In 2014, sunitinib was
      switched to axitinib when further radiologic progression was observed. In 2015,
      the patient was referred to Yazawa clinic for homecare urology when hospital
      visits became difficult due to cancer pain and bilateral lower-extremity muscle
      weakness. Cancer pain was controlled using acetaminophen and a fentanyl patch.
      During the administration of axitinib, a CTCAE grade 1 vocal disorder was
      detected. We reduced the axitinib dose from 10 mg to 6 mg, and valsartan and an
      antiflatulent were administered due to CTCAE grade 2 hypertension and diarrhea,
      respectively. Axitinib administration continued until the patient died. He had
      survived more than 11 years following the detection of lung metastasis. In this
      patient, a good balance between cancer treatment and palliative care was achieved
      through the application of homecare urology. In a super-aged society such as
      Japan, urologists with an awareness of Zaitaku Medicine, a Japanese style of
      homecare that provides continuing appropriate medical treatment and welfare
      support to patients with access barriers to hospital treatment to enable them to
      live out the remainder of their lives with dignity, may play a key role in the
      development of Zaitaku Medicine.

PMID- 29650822
TI  - [A Case of Poorly Differentiated Carcinoma of Unknown Primary Site with Risk of
      Choriocarcinoma Syndrome Effectively Treated with Reduced Bleomycin,Cisplatin
      ,Etoposide Combination Regimen(BEP Regimen)].
AB  - A 64-year-old man visited his physician complaining of bilateral gynecomastia and
      left shoulder pain. Chest X-ray showed multiple bilateral masses in the lung, and
      he was referred to our hospital. Radiographical findings, elevation of serum
      total hCG, and histological findings of the cervical lymph node revealed multiple
      pulmonary, nodal, and brain metastases of poorly differentiated carcinoma of an
      unknown primary site with choriocarcinoma components. He was administered a
      regimen of reduced bleomycin, cisplatin, etoposide combination(reduced BEP
      regimen)to reduce the risk of acute respiratory failure with intra-alveolar
      hemorrhage related to post-chemotherapy early tumor necrosis. After chemotherapy,
      the tumor marker hCG levels were almost restored to normal levels, and
      radiography showed he had achieved a clinical partial response.

PMID- 29650823
TI  - [Safety and Efficacy of TAS-102 with Bevacizumab for the Treatment of
      Unresectable Metastatic Colorectal Cancer - A Case Report].
AB  - Chemotherapywith TAS-102 with bevacizumab(Bmab)is a new treatment for metastatic
      colorectal cancer. A 67-year-old male patient with synchronous multiple liver
      metastases was treated with TAS-102 with Bmab as a fifth-line chemotherapy. It
      was demonstrated that liver metastases decreased in size by1 3%bycomputed
      tomography(CT)after 3 months of TAS-102 with Bmab therapy. The Grade 3 or worst
      adverse event that was experienced was neutropenia. The patient was able to
      continue treatment with TAS-102 with Bmab for 6 months. TAS-102 with Bmab
      treatment was safetyand efficacious as a late-line chemotherapytreatment for
      metastatic colorectal cancer.

PMID- 29650824
TI  - [A Case Report of Appendiceal Cancer Complicated Appendicitis Treated with Single
      Incision Laparoscopic Ileocecal Resection].
AB  - We report a case of appendicitis with an abscess that was treated with single
      incision laparoscopic ileocecal resection with D2 lymphadenectomy because of
      intraoperative suspicion of appendiceal cancer. A 73-year-old woman was admitted
      to the hospital because of right lower abdominal pain. She was diagnosed with
      appendicitis with an abscess. Although single-incision laparoscopic appendectomy
      was planned, appendiceal cancer was suspected from intraoperative findings.
      Therefore, we performed single-incision laparoscopic ileocecal resection with D2
      lymphadenectomy. The pathological result was moderately differentiated
      adenocarcinoma in the appendix. Because of the high risk of fStage II appendiceal
      cancer, adjuvant chemotherapy was administered. Neither recurrence nor metastasis
      have been detected 7 months after surgery.

PMID- 29650825
TI  - [Successful Breast Conserving Surgery for Simultaneous and Ipsilateral Multiple
      Breast Carcinomas of Young Patient - A Case Report].
AB  - We report a case of a simultaneous and ipsilateral multiple breast carcinoma.The
      patient was 35-year-old woman.She was noticed a breast lump on her right breast,
      and visited our hospital.Mammography showed a tumor accompanied by spiculation on
      her right breast.Ultrasonography revealed 2 tumors with irregular margins, 23mm
      in diameter and 12mm in diameter, and were observed on C area of her right
      breast.The continuity of the 2 tumors was not clear.Core needle biopsies for each
      breast tumors led to a diagnosis.The pathological diagnosis was invasive ductal
      carcinoma.We checked up whole body. There was no metastatic lesion.We performed
      breast conserving surgery and sentinel node biopsy.The pathological diagnosis was
      invasive ductal carcinoma, positive for estrogen receptor and progesterone
      receptor, negative for HER2/neu.The Ki-67 positive cell index was 30%.The
      surgical margin was negative.We diagnosed T2N0M0=Stage II A.She was started the
      endocrine therapy by LH-RH agonist and tamoxifen.Four years after surgery, she
      was well without metastases.

PMID- 29650826
TI  - [A Case in Which S-1 plus CDDP and S-1 Therapy Responded to Liver Metastasis
      Recurrence after Gastric Cancer Operation].
AB  - A 55-year-old man underwent distal gastrectomy and D2 lymph node dissection for
      type 2 gastric cancer of the antrum. One year later, CEA elevation was
      discovered, and contrast-enhanced abdominal computed tomography(CT)revealed a 40
      mm mass in the liver(S8), which was judged to be a metastatic recurrence of the
      gastric cancer.S -1 plus CDDP was administered in 5 courses, followed by regular
      treatment with S-1 alone.Two years after the recurrence was diagnosed, the
      patient's CEA level was found to be normal, and CT revealed almost total
      scarring.After 2 more years, there was still no sign of recurrence, so, with the
      patient's consent, we discontinued the chemotherapy.Eight years after the
      gastrectomy, a 10mm nodular shadow was observed in the left lower lung lobe, and
      resection was performed.Despite the earlier diagnosis of gastric adenocarcinoma,
      this mass was considered a primary lung adenocarcinoma, and the patient died of
      small-cell lung cancer 11 years and 8 months after the gastrectomy.It is notable
      that the liver metastasis in this case responded to the S-1 plus CDDP and S-1
      therapies, and this response is considered in light of the literature.

PMID- 29650827
TI  - [A Case Report of Complete Resection of the Recurrence Small Intestinal Carcinoma
      with Abdominal Wall Repair Using Femoral Fascia].
AB  - The patients had Hartmann's operation for rectal cancer when she was 61 years
      old. After that, she underwent the operation for small bowel cancer when she was
      68 years old. After 5 months, the only metastatic lesion was detected near the
      Scolon stoma. For the first therapy, She received chemotherapy(mFOLFOX6 plus
      bevacizumab)and had a reducing effect. She was introduced to our hospital for the
      purpose of resection of the recurrent lesion. CT scan detected a nodule near the
      Scolon stoma with FDG uptake for PET-CT scan. The lesion was resected with S
      colon stoma. The abdominal wall defect was so large, we performed abdominal wall
      plasty with a femoral fascia patch. Seven months after surgery, there is no
      recurrence. Small bowel tumor is a rare case. This disease frequency about 0.1
      0.3% and the treatment strategy is not well established. We reported that
      complete resection of the recurrence small intestinal carcinoma with abdominal
      wall repair using femoral fascia after the chemotherapy.

PMID- 29650828
TI  - [A Case of Locally Advanced Intrahepatic Cholangiocarcinoma Successfully Treated
      by Conversion Surgery after Hepatic Arterial Infusion Chemotherapy and Radiation
      Therapy].
AB  - The patient was a 63-year-old man. Computed tomography(CT)showed a 99mm in
      diameter low-density mass in hepatic segments 4 and 8 as the main locus. This
      tumor was diagnosed as intrahepatic cholangiocarcinoma and was suspected to
      invade to left and right Gleason's sheath, and radical cure was judged
      impossible. After hepatic arterial chemotherapy and radiotherapy were performed,
      tumor shrinkage was confirmed, and tumor markers also became negative. So he was
      referred to our hospital for surgical indication. CT revealed that the tumor did
      not invade to the left Gleason's sheath. After percutaneous transhepatic portal
      embolization, hepatic right trisectionectomy was performed. He was administered
      gemcitabine as an adjuvant chemotherapy for 1 year. One year 5 months after
      surgery, the patient is alive without relapse. Preoperative hepatic arterial
      chemotherapy and radiotherapy could be an effective treatment for unresectable
      locally advanced intrahepatic cholangiocarcinoma.

PMID- 29650829
TI  - [A Case of Stage IV Gastric Cancer Which Showed Pathological Complete Response
      after Neo-Adjuvant Chemotherapy].
AB  - We report a case of Stage IV gastric cancer showing pathological complete
      response(pCR)after neo-adjuvant chemotherapy( NAC)using S-1 and
      oxaliplatin(SOX).A woman 73-year-old was diagnosed as harming type 3 Stage IV
      gastric cancer with para-aortic lymph node(PAN)metastasis.She underwent 4 courses
      of NAC with SOX regimen.After the treatment, both the primary tumor and the
      metastatic PAN decreased in size remarkably.She underwent distal gastrectomy with
      D2 plus PAN dissection with curative intent.Pathological diagnosis revealed
      complete disappearance of cancer cells in both the primary lesion of the stomach
      and all dissected lymph nodes, confirming pCR.She is alive without recurrence 4
      months after surgery.

PMID- 29650830
TI  - [Curative Resection for Unresectable Locally Advanced Colorectal Cancer Following
      Intensive Chemotherapy plus Molecular Targeted Agent - Report of Three Cases].
AB  - Intensive chemotherapy plus molecular targeted agent improve overall survival for
      patients with unresectable colorectal cancer.We performed laparoscopic surgery
      following intensive chemotherapy of mFOLFOX6 or FOLFIRI plus molecular targeted
      agent for 3 patients with unresectable locally advanced colorectal cancer with
      abscess formation.A 60-year-old man was diagnosed as having unresectable rectal
      cancer with abscess formation and underwent curative resection after partial
      response following chemotherapy.A 42-year-old woman was diagnosed as having
      unresectable sigmoid colon cancer with abscess formation and underwent curative
      resection after partial response following chemotherapy.A 56-year-old woman was
      diagnosed as having unresectable sigmoid colon cancer with abscess formation and
      underwent curative resection after partial response following chemotherapy.They
      are alive after surgery for 69, 74 and 72 months, respectively.Intensive
      chemotherapy plus molecular targeted agent for unresectalbe locally advanced
      colorectal cancer with abscess formation will be one of useful strategies for
      minimum invasive surgery and effective local control.

PMID- 29650831
TI  - [Four Cases of Resected cN2 Stage III A Non-Small-Cell Lung Cancer after
      Induction Chemotherapy].
AB  - Four patients with non-small-cell lung cancer(NSCLC), diagnosed with cN2 stage
      III A disease, by using CT and FDG-PET/ CT imaging, received 2 or 3 courses of
      platinum-based combination chemotherapy.The patients achieved partial response
      after chemotherapy and underwent surgery.Complete tumor resection was performed
      via upper lobectomy for 3 patients, but in 1 patient, interlobar metastatic lymph
      nodes remained after middle and lower bilobectomy.Two courses of postoperative
      chemotherapy were administered to 3 patients, but 1 patient could not receive
      postoperative chemotherapy due to complications.One patient, in whom lymph node
      metastasis completely disappeared after induction chemotherapy, is still alive
      and without disease recurrence for 7 years.Another patient, with the presence of
      only one intralobar metastatic lymph node after chemotherapy, died of brain and
      meningeal metastases, 3 years after surgery.Two other patients, with multiple pN2
      lymph nodes after chemotherapy, died of early intrathoracic local relapse,
      indicating that prognosis is influenced by response to chemotherapy, especially
      in patients with poor N-downstaging.Improvements in response to induction therapy
      by using intensive chemotherapeutic regimens, concurrent radiotherapy, and strict
      patient selection, limited to N-downstaged cases, are needed for successful
      surgery outcomes in patients with cN2 stage III A NSCLC who have received
      induction therapy.

PMID- 29650832
TI  - [A Case of Long-Term Survival in Gastric Cancer with Multiple Liver Metastases
      Successfully Treated by Conversion Surgery after S-1 plus Cisplatin Combination
      Therapy].
AB  - A 49-year-old man was diagnosed with advanced gastric cancer, with a chief
      complaint of epigastric discomfort. Computed tomography revealed multiple liver
      metastases. S-1 plus cisplatin therapy was administered as first-line
      chemotherapy, and after 4courses, the liver metastases markedly reduced. Total
      gastrectomy with D2 lymphadenectomy and a needle biopsy of segment 2 of the liver
      were performed. Histopathological examination revealed no viable cancer cells in
      the resected stomach, lymph nodes, or liver tissue. The primary tumor was defined
      as Grade 3 by histopathological examination. Adjuvant chemotherapy with S-1 was
      administered for 1 year. The patient is alive without recurrence more than 6
      years after surgery.

PMID- 29650833
TI  - [A Case of Local Recurrence of Descending Colon Cancer with Ileus Obstruction and
      Lung, Liver and Brain Metastasis].
AB  - We report a 50-year-old man with local recurrence of descending colon cancer with
      ileus obstruction and brain metastasis, 2 years 6 months after initial resection
      due to perforation of descending colon cancer(Hartmann procedure, D2 lymph node
      resection, Stage II, tub2). He complained of left upper abdominal pain and
      abdominal fullness. He also complained of paresis of the right upper extremity
      and of experiencing convulsions 1 month before admission. He was diagnosed with
      local recurrence of descending colon cancer, based on findings of contrast
      radiography and the presence of colonic fiber. We subsequently performed
      transanal decompression as a bridge to surgery and performed partial resection of
      the local recurrence in the anastomosis at the descending colon and ileum
      involved with the cancer 2 weeks after decompression. In addition, multiple lung
      and liver metastases, and solitary brain metastasis(2.5 cm in size located in the
      left side of the parietal region) were detected by cerebral plain computed
      tomography. However, he refused both chemotherapy after surgery, as well as
      further surgery and/or radiation therapy for the brain metastasis. He desired to
      return to his home as soon as possible. In order to improve his quality of
      life(QOL), in-home treatment involving the best supportive care(BSC)conservative
      therapiesincluding, anticonvulsant and anti-intracranial hypertension drugs-were
      administered to prevent brain metastasis symptoms, such as paresis of the right
      upper extremities and convulsions. He was discharged from our hospital 14 days
      after surgery. Regrettably, he died due to bronchial asthma 75 days after
      palliative surgery in his home.

PMID- 29650834
TI  - [Asynchronous Bilateral Neuroendocrine Breast Carcinoma - A Case Report].
AB  - We report a case of asynchronous bilateral neuroendocrine breast carcinoma. The
      patient was a 49-year-old woman presenting with a bloody nipple discharge from
      the right breast. We suspected intraductal papilloma and performed a
      microdochectomy. A pathological analysis of the resected specimen confirmed the
      diagnosis as neuroendocrine carcinoma. The tumor was positive for estrogen
      receptor, progesterone receptor, chromogranin A, and synaptophysin, but negative
      for the HER2/neu marker. The Ki-67 labeling-index was 40%. As the tumor margin
      was positive, breast-conserving surgery plus level II axillary lymph node
      dissection was performed. After surgery, radiotherapy(total dose of 50 Gy)was
      administered for treating residual breast involvement. Adjuvant hormonal therapy
      was performed for 5 years. Ten years after surgery, ultrasonography revealed a
      12mm irregular hypoechoic mass in the left breast. The mass was diagnosed as a
      solid tubular carcinoma based on core needle biopsy findings. Subsequently, we
      performed breast-conserving surgery. The pathological diagnosis was a
      neuroendocrine carcinoma, and the tumor was positive for estrogen receptor,
      progesterone receptor, chromogranin A, synaptophysin, and CD56, but negative for
      the HER2/neu marker. The Ki-67 labeling-index was 50%. We report our experiences
      with a rare case of asynchronous bilateral neuroendocrine breast carcinoma. In
      this case, ultrasonography was a useful modality for detecting both the lesions.

PMID- 29650835
TI  - [Diagnosis of a Non-Invasive Ductal Carcinoma, Assisted by Long-Term Follow-Up of
      Spontaneous Nipple Discharge - A Case Report].
AB  - We report a case of a non-invasive ductal carcinoma revealed on long-term follow
      up of spontaneous nipple discharge. The patient, a 36-year-old woman, had noticed
      spontaneous nipple discharge from both breasts over a 3-year period. Mammography
      and ultrasonography did not reveal any lesions in the breasts. The nipple
      discharge from her left breast stopped 36 months after initial clinical
      assessment. However, the nipple discharges from her right breast transformed into
      a bloody discharge from a single duct. Ultrasonography showed a tumor, 6mm in
      diameter, in the upper-outer quadrant of her right breast. A core needle biopsy
      for breast tumor led to a pathological diagnosis of non-invasive ductal
      carcinoma. We conducted a whole-body clinical examination but no metastatic
      lesions were detected. Subsequently, we performed breastconserving surgery and
      sentinel lymph node biopsy. The pathological diagnosis was non-invasive ductal
      carcinoma in situ. The tumor was positive for estrogen and progesterone
      receptors, but negative for HER2/neu. The Ki-67 labeling index was 5%. The
      surgical margin was negative. We diagnosed the tumor as TisN0M0=Stage 0.
      Endocrine therapy comprising tamoxifen (20mg/day)was initiated. Four years after
      surgery, she was well without any metastases.

PMID- 29650836
TI  - [A Case of Advanced Esophagogastric Junction Cancer Responding to S-1 Neoadjuvant
      Chemotherapy].
AB  - A 56-year-old man was diagnosed with advanced adenocarcinoma of the
      esophagogastric junction. He received 1 course of neoadjuvant chemotherapy with S
      1. After neoadjuvant chemotherapy, the primary tumor showed a remarkable decrease
      in size. Subtotalesophagectomy, D2 lymph node dissection, and reconstruction with
      a gastric tube through the posterior mediastinal route were performed.
      Pathological examination showed that most of the cancer cells had been destroyed,
      with a part where adenocarcinoma mucosa was seen. We successfully treated a case
      of advanced adenocarcinoma of the esophagogastric junction, with neoadjuvant S-1
      chemotherapy and surgicalresection.

PMID- 29650837
TI  - [Laparoscopic Distal Gastrectomy for Elderly Patients with Advanced Gastric
      Cancer and Gastric Outlet Obstruction - A Case Report].
AB  - A 90-year-old female patient was admitted to our hospital with a chief complaint
      of vomiting.Gastroscopy revealed type 3 gastric cancer and gastric outlet
      obstruction(GOO).Abdominal computed tomography revealed thickening of the antral
      wall and suggested the presence of 3 perigastric lymph node metastases, but there
      was no ascitic fluid or distant metastasis.The clinical diagnosis was
      T4a(SE)N2H0CYXP0M0, Stage III B, according to the Japanese Classification of
      Gastric Carcinoma.Her general conditions including kidney and cardiac function
      were good, we considered that she was able to tolerate radical distal
      gastrectomy.We planned laparoscopic distal gastrectomy(LDG)and D2 lymphadenectomy
      after getting sufficient informed consent.The patient experienced an uneventful
      post-operative recovery, and was discharged in good health 11 days after surgery.

PMID- 29650838
TI  - [Two Cases of Hepatic Encephalopathy after Chemotherapy for Metastatic Colorectal
      Cancer].
AB  - We reported 2 cases of hepatic encephalopathy after chemotherapy for advanced
      colorectal cancer. Case 1: A 49-year-old male was diagnosed advanced sigmoid
      colon cancer with peritoneal dissemination, multiple liver metastasis and
      multiple osseous metastasis. After resection of primary lesion, we administered
      mFOLFOX6 plus bevacizumab combination therapy. He was in comatose(Japan coma
      scale 200)3 days after 2 courses of administration of this regimen. Case 2: A 57
      year-old female was diagnosed advanced rectal cancer with multiple huge liver
      metastasis and multiple osseous metastasis. We administered mFOLFOX6 plus
      panitumumab combination therapy. She was in comatose(Japan coma scale 100)3 days
      after 10 courses of administration of this regimen. In both cases, radiographic
      imaging showed no abnormal sign and blood examination revealed a high level of
      serum ammonia. We diagnosed their disturbance of consciousness as a symptom of
      hepatic encephalopathy. Branched-chain amino acid infusion rapidly improved
      disturbance of consciousness. We must consider the symptom, hepatic
      encephalopathy in patients receiving chemotherapy for advanced colorectal cancer.

PMID- 29650839
TI  - [A Case of Splenic Metastasis from Serous Surface Papillary Carcinoma of the
      Peritoneum Treated by Laparoscopic Splenectomy].
AB  - A 50-year-old woman with abdominal fullness, lower abdominal pain, elevated serum
      CA125, and ascites, underwent neoadjuvant chemotherapy with 6 courses of
      PTX/CBDCA followed by total hysterectomy, bilateral salpingo-oophorectomy,
      omentectomy, and intrapelvic peritoneal stripping based on a diagnosis of serous
      surface papillary carcinoma(SSPC) of the peritoneum. Complete response(CR)was
      shown after adjuvant chemotherapy with 3 courses of the same regimen. After 6
      months, serum CA125 level re-increased and abdominal CT showed small low density
      areas in the patient's spleen and the perisplenic fat tissue. After the
      additional chemotherapy with 3 courses of PTX/CBDCA were performed based on a
      diagnosis of metastatic lesion from SSPC, anaphylactic shock occurred as the
      severe adverse event. The patient was given 9 more courses of the chemotherapy
      changed the regimen to PTX/CDDP. The splenic metastatic lesion had grown rapidly
      in the followed CT and then, laparoscopic splenectomy with peritoneal resection
      was performed based on a diagnosis of splenic metastasis from SSPC. The
      pathological examinations showed the tumor to be a splenic metastasis and
      peritoneal dissemination from SSPC. No recurrent lesion has been detected in the
      9 months since removal of the splenic metastasis without adjuvant chemotherapy
      and the patient has survived for 4 years and 6 months since initial treatment.

PMID- 29650840
TI  - [A Case of Effective Palliative Care with CART for Refractory Ascites Associated
      with Cancerous Peritonitis of Gastric Cancer].
AB  - Refractory ascites associated with cancerous peritonitis causes abdominal tension
      and reduced oral intake. Frequent ascites drainage can cause rapid worsening ofa
      patient's general condition. Cell-free and concentrated ascites reinfusion
      therapy (CART)for refractory ascites was first covered in 1981, and the general
      conditions ofpatients and their symptoms could be improved after undergoing CART.
      Herein, we report a case of effective palliative care with CART for refractory
      ascites associated with cancerous peritonitis. A 66-year-old man was admitted to
      our hospital because ofabdominal distension. Computed tomography revealed the
      presence ofascites and gastric wall thickness; upper gastrointestinal endoscopy
      revealed an ulcerated lesion with raised margins on the body ofthe stomach.
      Biopsy ofthis lesion confirmed the diagnosis ofadenocarcinoma, and he was
      diagnosed with gastric cancer(M, Type 3, cT4a[SE], cN0, cH0, cP1, cM1, cStage
      IV). He underwent palliative care for ascites, followed by FLTAX regimen
      chemotherapy(5-fluorouracil[5-FU]and Leucovorin[LV]combined with weekly
      paclitaxel[PTX]). He received CART for 8 courses without complications, and his
      symptoms improved after receiving CART. He survived for about 18 months, and
      could ingest a normal diet for a long time. CART may be favorable in palliative
      care for massive ascites associated with cancerous peritonitis.

PMID- 29650841
TI  - [A Case of Advanced Esophageal Cancer Successfully Treated with Multidisciplinary
      Therapy].
AB  - We report a case of advanced esophageal cancer that was successfully treated
      using chemotherapy, operation, and chemoradiotherapy. A 66-year-old man with
      advanced esophageal cancer(Mt, O-Is, T4[N0.7-stomach], N2, M0, Stage III)was
      administered chemotherapy(docetaxel[DOC], cisplatin[CDDP], and 5-fluorouracil[5
      FU]: DCF). As the esophageal tumor achieved complete clinical response after 2
      courses of chemotherapy, lymph node dissection and proximal gastrectomy were
      performed for the residual tumor. Abdominal CT 3 months after surgery revealed
      lymph node swelling. He was diagnosed with lymph node metastasis and was
      administered chemoradiotherapy. After chemoradiotherapy, liver metastasis was
      revealed, and he underwent immune checkpoint inhibitor immunotherapy. Despite the
      administration of immune checkpoint inhibitors, the liver metastasis developed,
      so he was treated with S-1 chemotherapy. S-1 chemotherapy resulted in a favorable
      response, and almost all metastatic lesions decreased. The patient is alive 12
      months after S-1 chemotherapy without any signs of tumor regrowth.

PMID- 29650842
TI  - [Evaluated Cases of Anastomotic Recurrence in Colorectal Cancer].
AB  - Anastomotic recurrence in 6 colorectal cancer cases during the postoperative
      surveillance between 2008 and 2015 was evaluated retrospectively. Five cases had
      undergone DST anastomosis for sigmoidectomy and proctectomy. They had a
      pathological tendency to have T3 tumor and deeper, positive lymph node metastases
      and positive lymphatic and vascular invasion. There were 2 cases with the
      anastomotic recurrence diagnosis 6 to 8 months after the primary tumor resection
      while 4 resected cases had recurrent tumor depth of T3, though 3 cases were
      diagnosed 1 year after the primary tumor resection. Anastomotic recurrence should
      be considered a few months after primary tumor resection.

PMID- 29650844
TI  - [Super-Elderly Recurrent Rectal Cancer Effectively Treated with Chemotherapy for
      Three Years - Report of a Case].
AB  - The safety and feasibility of the chemotherapy for super-elderly patients over 85
      years old have not been clarified yet. We report an extremely aged patient with
      recurrent rectal cancer that was successfully treated with chemotherapy. A 85
      year-old woman underwent Hartmann procedure for rectal cancer. Nine months after
      surgery, CT scan revealed liver metastases in S5 and S7. We administered
      capecitabine plus bevacizumab chemotherapy. Liver metastases were disappeared
      after 6 courses. Although grade 2 hypertension was appeared, no other adverse
      event occurred. However, due to lung metastases, we attempted irinotecan plus
      bevacizumab as second line treatment. After 10 courses, general fatigue was
      gradually developed, so we changed the frequency of chemotherapy from biweekly to
      triweekly administration. The patient's performance status score has been kept 0,
      and she has been under treatment as an outpatient for 3 years. The chemotherapy
      for extremely aged patients with recurrent colorectal cancer was suggested to be
      safe and feasible under the adequate dose reduction and intervaladjustment.

PMID- 29650843
TI  - [A Case of Gastric Carcinoma with Peritoneal Dissemination Treated with Curative
      Resection Following Trastuzumab plus Capecitabine plus Cisplatin Combined
      Therapy].
AB  - A 67-year-old man was referred to our hospital with a diagnosis of type 3 gastric
      cancer in lower third of the stomach. Computed tomography(CT)scan showed no
      distant metastasis, but peritoneal dissemination from gastric cancer. A
      laparoscopic exploration diagnosed pStage IV gastric cancer with peritoneal
      dissemination. Trastuzumab, capecitabine and cisplatin therapy was administered
      for initially unresectable gastric cancer. After 6courses of chemotherapy,
      primary lesion and lymph node metastasis shrank, and the peritoneal dissemination
      did not worsen by CT scan. The second laparoscopic exploration showed no apparent
      dissemination or metastatic cancer cells. Total gastrectomy with D2 lymph node
      dissection, partial colectomy and cholecystectomy were performed with curative
      intent. The pathological diagnosis was ypT3N1P0CY0, Stage II B, and the
      histological response of primary tumor after chemotherapy was categorized as
      Grade 1a. The patients is alive during 24 months after surgery with no evidence
      of recurrence.

PMID- 29650845
TI  - [A Case Report of SOX Treatment for Primary Duodenal Carcinoma with Liver
      Metastasis].
AB  - We report a case of effective S-1 plus oxaliplatin (SOX) treatment for duodenal
      cancer with liver metastases. The patient was a 70-year-old female diagnosed with
      duodenal carcinoma that was unresectable because of liver metastasis(cT4N1M1,
      cStage IV in UICC 7th). She received SOX treatment(100mg/m / 2 of oxaliplatin on
      day 1 combined with 40 mg/day of S-1 twice daily on days 1-14, was repeated every
      3 weeks). After 4 courses, a partial response was confirmed by computed
      tomography and no severe adverse events were observed. However, during the 5th
      courses, several new liver metastases were observed, so we changed to weekly
      paclitaxel treatment. This case suggests that SOX treatment may be an effective
      chemotherapy for advanced primary duodenal carcinoma.

PMID- 29650846
TI  - [Two-Stage Radical Resection of a Case of Colon Cancer with Abdominal Wall
      Invasion and Cholangiocarcinoma].
AB  - A woman in her 50s was admitted to our hospital with fever and lower abdominal
      swelling. Abdominal CT/MRI examinations revealed irregular thickening of the
      transverse colon wall, which was attached to a subcutaneous abscess. An abdominal
      wall mass, a patent urachus, and a tumor in the 5th segment of the liver were
      also noted. Colonoscopy revealed type 2 advanced transverse colon cancer. The
      solitary, sessile tumor was observed at the apex of the bladder under cystoscopy,
      suggesting the formation of the urachal carcinoma. Transcutaneous liver biopsy
      obtained from the liver tumor indicated adenocarcinoma, which was morphologically
      different from the existing transverse colon cancer. Right hemicolectomy with
      resection of the umbilicus, abdominal wall, urachus, and part of the bladder wall
      was performed. Diagnosis of the transverse colon cancer invading the abdominal
      wall and bladder was confirmed by histopathological examination. Hepatectomy was
      performed in the next surgery, and the tumor was histopathologically diagnosed as
      an intrahepatic cholangiocarcinoma. Both the transverse colon cancer and the
      intrahepatic cholangiocarcinoma were radically resected. Radical surgical
      diagnostic resection may be valuable in cases of multicentric cancers of unknown
      primary origin, if radical resection of each individual tumor is required.

PMID- 29650847
TI  - [A Case of Adult Undifferentiated Sarcoma of the Liver with Intraatrial
      Metastasis].
AB  - A 24-year-old woman was admitted to the hospital for abdominal pain. Abdominal
      contrast-enhanced computed tomography( CT)revealed a cystic mass measuring 11*8
      cm in the left lobe of the liver with extravasation. Vascular embolization was
      performed, but extravasation remained on CT images. She was then transferred to
      our hospital. We performed an emergency extended left hepatectomy.
      Histopathological examination revealed solid proliferation of spindle-shaped
      cells. Immunohistochemical staining showed that the tumor cells were positive for
      vimentin and negative for AE1/AE3. Thus, a diagnosis of undifferentiated sarcoma
      was confirmed. Multiple recurrent tumors were recognized on CT images of the lung
      and right atrium taken 1 year and 10 months post-surgery. Partial resection of
      the tumor was performed for the right atrial mass, the left lingular segment, the
      left inferior lobe, and the right middle lobe. Pathological diagnosis confirmed
      metastasis of undifferentiated sarcoma from the liver. Chemotherapy consisting of
      vincristine, actinomycin D, and cyclophosphamide(VAC) was not effective, and the
      patient died 31 months after the primary surgery. Undifferentiated sarcoma of the
      liver is a rare malignant mesenchymal tumor, whose occurrence is extremely rare
      in adults. Although surgical treatment is the first choice, outcomes remain poor.
      Multimodality treatment should be used to improve the outcome.

PMID- 29650848
TI  - [A Successful Treatment of Locally Advanced Breast Cancer with Using Mohs' Paste
      and Chemotherapy - A Case Report].
AB  - Foul smell and large amounts ofexudate, bleeding are the most common and serious
      symptoms with locally advanced breast cancer(LABC). Mohs' paste is made ofa
      mixture ofzinc chloride and used for treatment ofmalignant skin tumors. Recently
      some reports show that Mohs' paste is useful for treatment of malignant tumor
      including unresectable breast cancer and skin metastasis ofcancer. Mohs' paste is
      useful for reducing symptoms such as foul smell and exudate, Bleeding. We report
      a successful case of treatment for LABC with using Mohs' paste and chemotherapy
      and surgery.

PMID- 29650849
TI  - [A Case of Resected Reactive Lymphoid Hyperplasia of Liver Suspected of
      Hepatocellular Carcinoma].
AB  - A 64-year-old woman who had chronic type C viral hepatitis was referred with a
      liver tumor detected by magnetic resonance imaging(MRI). She had a history of
      rheumatoid arthritis which was treated by methotrexate. Ethoxybenzyl-MRI(EOBMRI)
      showed a low signal in the T1-weighted imaging, a high signal in the T2-weighted
      imaging and a low signal in the hepatobiliary phase. The tumor was 7 millimeters
      in diameter at S4, and exhibited enhancement in the arterial phase and wash out
      in the portal phase by contrast enhanced CT. Imaging findings suggested
      hepatocellular carcinoma, and we performed partial hepatectomy of S4.
      Histopathological examination confirmed reactive lymphoid hyperplasia(RLH)of
      liver. RLH of liver is a rare benign lesion and it is necessary to consider RLH
      as a differential diagnosis of the liver tumor.

PMID- 29650850
TI  - [Analysis of Hepatectomy for Liver Metastasis from Gastric Cancer].
AB  - INTRODUCTION: The indication of hepatectomy for liver metastasis from gastric
      cancer has not been definitely established. PATIENTS AND METHODS: Among 12 cases
      that were performed hepatectomy for liver metastasis from gastric cancer in our
      institute from 2008 to 2016, we analysed prognosis and the benefit of surgical
      resection. RESULTS: The overall 5-year survival rates of all cases were 42.3%,
      and median survival time was 2 years. The overall survival rates of synchronous
      metastasis was 59.3%and of metachronous metastasis was 0%. Recurrence rate of all
      cases within 1 year was 75%. There was no long-term survivor for metachronous
      metastasis because of its early recurrence though it was solitary liver tumor.
      CONCLUSION: We should carefully indicate surgical resection for liver metastasis
      from gastric cancer.

PMID- 29650851
TI  - [A Case of Isolated Lateral Pelvic Lymph Node Recurrence after TME for Early
      Lower Rectal Cancer Treated with Laparoscopic Lateral Lymph Node Dissection].
AB  - There are no established treatment protocol for isolated lateral lymph node
      recurrence in patients with T1 lower rectal cancer, because such case is very
      rare. In our institution, this is the only recorded case of lateral node
      recurrence post-resection. It has been documented in several studies that salvage
      surgery for colorectal cancer improves prognosis. However, there were only 3
      reported cases found for lateral lymph node metastasis from colorectal cancer
      that underwent excision. In this study, we report a rare case of lateral lymph
      node recurrence after trans-anal resection for T1 lower rectal cancer wherein we
      performed laparoscopic right lateral pelvic lymph node dissection. The procedure
      was done safely without any complications. No recurrence noted on follow-up.
      Hence, we can perform resection of isolated lateral lymph node recurrence in
      selected patients to achieve good prognosis.

PMID- 29650852
TI  - [Experience of Nine Cases of Endoscopic Gastroduodenal Stenting for Malignant
      Gastroduodenal Obstruction].
AB  - BACKGROUND: We reported our results of endoscopic gastroduodenal stenting for
      malignant gastroduodenal obstruction. METHODS: This retrospective study
      investigated cases of malignant gastric and duodenal obstruction treated with
      gastroduodenal stenting between April 2014 and December 2016. RESULTS: The mean
      operative time was 34 minutes. The mean time to the first intake of solid food
      was 2.7 days, and the median time was 3 days. Complications were restenosis,
      vomiting, anemia, anorexia, and gastric pain. In 8 patients, the GOOSS score was
      improved. In 5 patients, the CONUT score was improved. In 6 patients, the albumin
      level was improved. The mean overall survival time was 130 days, and the median
      time was 112 days. CONCLUSION: Our study suggested that gastroduodenal stenting
      for malignant gastroduodenal obstruction was minimally invasive and improved
      quality of life(QOL)in a short time.

PMID- 29650853
TI  - [A Case of Combined Treatment Approach of Endoscopic Submucosal Dissection and
      Transanal Minimally Invasive Surgery for Radiation Induced Rectal Cancer].
AB  - It is hard to determine treatment strategy for radiation induced carcinoma,
      because radiation cause fibrosis to adjacent organ.The patient was in the 70's,
      who underwent 70 Gy radiation therapy for prostate cancer 5 years ago.He visited
      hospital because of fecal occult blood.Endoscopic examination revealed laterally
      spreading tumor(LST)in rectal front wall, and he referred to our hospital in
      purpose of endoscopic submucosal dissection(ESD).We performed ESD for LST,
      following transanal minimally invasive surgery to suture mucosal defect.He
      discharged out hospital 9 days after operation without any adverse event except
      anal pain.Suturing of mucosal defect after ESD might be potent to prevent
      postoperative complications in radiation induced rectal cancer.

PMID- 29650854
TI  - [A Case of Hyperammonemia Induced by Chemotherapy with 5-Fluorouracil for
      Metastatic Colon Cancer].
AB  - Systemic chemotherapy based on 5-fluorouracil(5-FU)is a standard treatment for
      unresectable or recurrent colon cancers. Here, we report a case of hyperammonemia
      induced by chemotherapy using 5-FU for metastatic colon cancer. An 84-yearold
      male patient with past histories of liver cirrhosis related to hepatitis C virus
      and renal dysfunction underwent an operation for the rectosigmoid colon cancer 8
      years ago. Three years after that operation, a local recurrence of the colon
      cancer was diagnosed, and chemotherapy using sLV5FU2 was initiated. The
      recurrence lesion reduced markedly by this chemotherapy, which was ceased 2 years
      ago. Two years after the cessation the recurrent tumor had been enlarged, and the
      chemotherapy using the same drugs at the same dose was performed. On the
      treatment day 3, he was emergently transported to our hospital due to the
      disturbance of consciousness. Since laboratory tests showed the high
      concentration of plasma ammonia and the progressed renal dysfunction with no
      other definite cause of obnubilation, he was diagnosed as the hyperammonemia
      induced by 5-FU. He was treated by administrating the branched-chain amino acids
      solutions combined with fluid therapy, which quickly recovered him from the
      encephalopathy. He is followed up without any chemotherapy because of his high
      age. When a patient treated with the chemotherapy using 5-FU is sent with the
      disturbance of consciousness, we should take hyperammonemia into consideration,
      especially when he or she has the hepatic or renal dysfunction.

PMID- 29650855
TI  - [A Case of Double Cancer of Intrahepatic Cholangiocarcinoma and Gastric Carcinoma
      with Difficult Diagnosis of the Primary Tumor with Peritoneal Metastasis].
AB  - Double cancer of intrahepatic cholangiocarcinoma and gastric cancer is rare. A 62
      year-old man underwent gastrectomy for gastric cancer. The pathological findings
      were tub1>tub2, m, ly0, v0, n0, Stage I A. Two years and a month later, a liver
      tumor(diameter of 3 cm)and a pelvic mass(diameter of 2.5 cm)were observed.
      Metastasis from gastric cancer was suspected and chemotherapy(SOX)was
      administered. However, after 5 courses, CT revealed worseningof the liver tumor
      (diameter of 12 cm)and pelvic mass(diameter of 3 cm). Intrahepatic
      cholangiocarcinoma and its peritoneal metastasis were also suspected. There was a
      limit to treatment with chemotherapy, and it was difficult to judge whether to
      target gastric cancer or intrahepatic cholangiocarcinoma for chemotherapy. In
      addition, the lesions were localized in the right lobe of the liver and the
      pelvis. Therefore, we decided to perform resection. As a second-stage operation,
      pelvic mass extraction and portal vein embolization were performed first. The
      pathological result of the pelvic mass assessment was mucinous carcinoma.
      Subsequently, expansive right hepatectomy was performed. The pathological
      findings were also suggestive of mucinous carcinoma, which was finally diagnosed
      as intrahepatic cholangiocarcinoma and peritoneal dissemination. Six months after
      the surgery, several recurrent nodules were observed in the pelvis and GEM plus
      CDDP was initiated. Currently, 1 year after surgery, there are no restrictions in
      the activities of daily life of the patient and he is treated on an outpatient
      basis.

PMID- 29650856
TI  - [A Case of Performed Right Colectomy with Pancreato-Duodenectomy for Transverse
      Colon Cancer Invased to Duodenum].
AB  - There is a clear consensus regarding the combined resection of organs with cancer
      invasion, patients with colon cancer. However, there are very few reports to our
      knowledge regarding the use of pancreato-duodenectomy(PD)for colon cancer
      patients with cancer invasion in the duodenum. We here report a colon cancer
      patient in whom we performed PD and right hemicolectomy, who showed favorable
      results with no recurrence. The patient was a 69-year-old woman. Her chief
      complaint was hypogastric pain. Her previous doctor performed colonoscopy and a
      colonoscopic biopsy, and detected a type 2 lesion, throughout the entire
      circumference of the transverse colon near the liver, and she was diagnosed with
      adenocarcinoma. From further imaging analyses, she was diagnosed as having
      transverse colon cancer with invasion into the superior mesenteric vein(SMV),
      duodenum, and pancreatic head, and No. 223 lymph node metastasis. The patient's
      cancer was concluded to be unresectable, and she underwent chemotherapy, namely
      mFOLFOX6 with cetuxiumab(Cmab). One course of mFOLFOX with Cmab, the patient
      decided to consult our hospital for a second opinion. We concluded that her
      cancer was resectable, so we performed PD, right hemicolectomy, and resection and
      reconstruction of a part of the SMV. The operation time was 5 hours 17 minutes,
      and total blood loss was 190 mL. The histopathological diagnosis was tub2,
      T4b(duodenum and, tissue surrounding the SMV), int, INF b, ly1, v2, PN1b,
      EX(+)/ND(PN+, v+), PM0(25 cm), DM0(14.3 cm), N1(1/ 20), H0, P0, M0, pStage III a.
      She was discharged 15 days after surgery with no complications, and thereafter
      received ajduvant chemotherapy(capecitabine with oxaliplatin)as an outpatient.
      After 3 courses, capecitabine with oxaliplatin was changed to capecitabine
      because she developed a nervous system disorder, and she was further treated for
      approximately about 6 months. She is doing well at the time of writing, with no
      recurrences for 2 years. We suggest that PD should be performed on colon cancer
      patients in which the colon cancer has invaded other organs and has been
      evaluated as being unresectable.

PMID- 29650857
TI  - [Two Cases of Locally Recurrent Rectal Cancer Undergoing Preoperative
      Chemoradiationtherapy].
AB  - Case 1 is a 68-year-old woman with locally recurrent rectal cancer(LRRC)developed
      5 years after resection of primary rectal cancer. The tumor seized right lateral
      side in pelvic. We performed tumor excision after preoperative chemoradiation
      comprised external beam radiation with oral S-1(tegafur/gimeracil/oteracil). He
      has been relapse-free for 3 years 3months after surgery. Case 2 is a 74-year-old
      man with LRRC developed 2 years after resection of primary rectal cancer. The
      tumor was located dorsal to anastomosis site in pelvic. We performed
      abdominoperineal resection for LRRC after preoperative chemoradiation with oral S
      1. He has been relapse-free for 2 years. It was suggested that preoperative
      radiotherapy combined with oral FU for local recurrence after rectal cancer may
      contribute to distant and local control.

PMID- 29650860
TI  - [End-of-Life Decision Making Support in Palliative Homecare].
AB  - Advance care planning is important in end-of-life decision making in home-based
      palliative care for both cancer patients and non-cancer patients.

PMID- 29650859
TI  - [A Retrospective Study of Preoperative Concurrent Chemoradiotherapy for Locally
      Advanced Resectable Rectal Cancer].
AB  - PURPOSE: To analyze chemoradiotherapy results for locally advanced rectal cancers
      at a single institution. METHODS: The study cohort comprised 12 patients with
      clinically diagnosed T3/4, NX, M0 adenocarcinomas of the rectum who received
      preoperative chemoradiotherapy. RESULT: Pathological complete response(pCR)were
      observed in 2/12(16.7%)patients and pathological downstaging in
      5/12(41.7%)patients, with generally mild adverse events. CONCLUSION: Preoperative
      che- moradiotherapy for clinical T3/4, NX rectal cancers significantly reduces
      local recurrences and improves prognoses.

PMID- 29650858
TI  - [A Case of Unresectable Advanced Gastric Cancer Treated by Seven Courses of
      Chemotherapy with Docetaxel, Cisplatin, and S-1Followed by Conversion Surgery
      Achieved Five Year Relapse Free Survival].
AB  - The patient is a 51-year-old man.Upper gastrointestinal endoscopy revealed
      gigantic type 3 gastric cancer.Enhanced abdominal CT demonstrated a gigantic mass
      of 15*7 cm in the stomach, and a large number of peritoneal dissemination with
      moderate amount of ascites.The patient was diagnosed with cT4aN3bM1(peritoneal
      dissemination), Stage IV gastric cancer(JPN ver8)and was treated by chemotherapy
      with docetaxel(40mg/m / 2 day 1)plus cisplatin(60mg/m2 day 1)plus S-1(80mg/m2 day
      1-14).After 7 courses of chemotherapy, peritoneal dissemination was
      disappeared.The patient received total gastrectomy and D2 lymphadenectomy as a
      conversion surgery.The pathological findings revealed a T0N0M0, stage 0; the
      tumor was determined to be Grade 3 owing to the chemotherapeutic effect.Without
      postoperative adjuvant therapy, the patient is alive without recurrence at the 5
      years follow-up after operation.

PMID- 29650861
TI  - [The Influence of the Timing of Ceasing or Withholding Chemotherapy in Home-Based
      End-of-Life Care in Patients with Incurable Solid Cancer - Release of an Interim
      Report of the Questionnaire Survey to Home Care Doctors in Japan].
AB  - BACKGROUND: The study analyzes a questionnaire on the potential discriminative
      characteristics of patients with incurable solidcancer, who either receivedor
      didnot receive palliative chemotherapy while receiving home-basedend -of-life
      care. From the standpoint of regional palliative care, we sought to investigate
      the influence of the timing of when chemotherapy was ceasedor withheldin home
      basedend -of-life care in patients with incurable solidcancer. We plannedthe
      project to obtain scientific evidence about the timing of ceasing or withholding
      chemotherapy. PATIENTS AND METHODS: The study includes all patients with
      solidcancer treatedwith or without palliative chemotherapy andwho diedat home in
      2016 in Japan. We delivereda postcardof invitation to participate in the
      questionnaire to more than 2,000 home care doctors in Japan. The questionnaires
      were registeredas online surveys from May to November 2017. The questionnaire
      data were analyzed using nonparametric methods. RESULTS: We obtained information
      from 576 patients at 170 medical facilities from May to August 2017, but the
      study is currently ongoing; hence, we have released an interim report of the
      questionnaire results. Among the patients, 40%receivedchemotherapy and 60%didnot
      since the time of the first incurable solidcancer diagnosis. CONCLUSION: The
      majority 60% of patients not receiving chemotherapy was a setback to our project.
      However, as the questionnaire survey continues, we wouldlike to analyze these
      data after collecting more results.

PMID- 29650862
TI  - [Caregivers Working in a Nursing Home Facility Utilizing a Simulation Program As
      an Effective Preventative Measure for Pressure Ulcers].
AB  - The purpose of this study was to clarify if a simulation program utilized by
      caregivers working in a nursing home is an effective preventative measure for
      pressure ulcers. The study sample consists of 35caregivers working in a nursing
      home in Osaka, Japan. The results show that knowledge and practice of preventive
      measures were significantly higher after using the simulation program for
      preventive care of pressure ulcers. Nurses and care workers need to cooperate
      with each other to improve quality of care.

PMID- 29650863
TI  - [Problems of Home-Visiting Speech-Language-Hearing Therapists in Dysphagia
      Management].
AB  - There are fewer reports by speech-language-hearing therapists than those by
      physical therapists or occupational therapists for visiting rehabilitation.
      Therefore, we examined the present situation with emphasis on professional roles
      of speech-language- hearing therapists working in visiting rehabilitation,
      patient tendency, and dysphagia rehabilitation. A questionnaire survey and
      interview survey were conducted on 6 speech-language-hearing therapists working
      in visiting rehabilitation. In the questionnaire, personal attributes, subject
      area, details of dysphagia rehabilitation, professional duties, and tendency of
      patient in charge were collected. In the interview survey, we asked about trends
      and request status, evaluation and training protocol for patients with dysphagia,
      activities related to pneumonia prevention, and future directions in the field.
      Results show that many linguistichearing experts worked with dysphagia patients,
      indicating that the needs for respiratory rehabilitation and dysphagia
      rehabilitation are high. In this survey, the environment surrounding visiting
      speech-language-hearing therapists and patients with dysphagia was clarified.

PMID- 29650864
TI  - [A Case of Home Care for Heart Failure].
AB  - A female in her 80s with a history of cerebral infarction and atrial fibrillation
      had repeated hospitalizations because of heart failure caused by ischemic
      myocardiopathy. She lived alone and received home care and support for self-care
      with involvement of multiple providers, enabling early detection of disease
      exacerbation and subsequent intervention. A new ischemic event was managed with
      percutaneous coronary intervention. With deterioration of renal function, her
      response to diuretics decreased, and dialysis was initiated. Home therapy was
      continued in cooperation with a dialysis center. Finally, the patient was
      admitted to a convalescent-type hospital equipped with dialyzers for ongoing
      dialysis. This case highlighted both the potential and limits of home therapy in
      management of heart failure. Active treatment and support for decision-making
      were also considered important.

PMID- 29650865
TI  - [Association of the Types of Dementia and the Incidence of Hypertension, Diabetes
      Mellitus, or Bone Fracture].
AB  - Patients with dementia tend to have other chronic diseases, such as hypertension
      or diabetes mellitus. As dementia progresses, patients tend to decline to a frail
      state, resulting in bone fracture. In this study, we examined the relationship of
      the types of dementia and the incidence of other diseases and bone fracture.

PMID- 29650866
TI  - [Identifying the Regional Features in the Visiting Nursing Station Trade Area
      Using GIS].
AB  - In order to clarify the characteristics of the area where the visiting nursing
      station is located, we conducted a study to identify the regional characteristics
      of the visiting nursing station in Ishikawa Prefecture, using geographical
      information system(GIS). We mapped the elderly population, aging rate, and
      location data for the visiting nursing station using QGIS, and created trade
      areas(Voronoi diagrams). The aging rate for each trade area is 22.4%(min 8.8% to
      max 44.6%), about 5 times. The difference in area is about 850 times as large as
      the central value of 9.2 km2(min 0.5 km2 to max 423.2 km2). In addition, there
      was a tendency for stations with a large trade area to have a higher aging rate
      than that of smaller stations. Understanding the characteristics of the area
      surrounding visiting nursing stations using GIS facilitates the clarification of
      potential needs and opportunities for providing visiting nursing services that
      are suitable for each area.

PMID- 29650867
TI  - [A Study on the Number of Offices for Home-Visit/Outpatient Day Long-Term Care in
      Noto Area, Based on Estimated Population - Analysis Using the Geographic
      Information System].
AB  - There has been a noticeable population decline in the Noto area. The Ministry of
      Land, Infrastructure, Transport and Tourism has determined the population size
      necessary for the establishment of daily living-related service businesses and,
      if the population falls below this, there is a possibility of businesses
      withdrawing from the area. In this research, we examine the number of home visit
      and daycare businesses established in the Noto area in 2025, using the geographic
      information system (GIS). The number of sites of businesses established was
      calculated using data published by the National Institute of Population and
      Social Security Research, and the Ministry of Land, Infrastructure, Transport and
      Tourism. Next, I depicted a buffer with a radius of 15 km from the establishment
      and confirmed the blank area of the service. Under the condition that the
      placement of sites is 80%, almost all the municipalities have exceeded the number
      of home visit care facilities and the number of daycare facilities. In the buffer
      analysis, blank areas were found in the north. To maintain these services,
      efforts by groups other than profit-oriented organizations are necessary,
      especially in the north of Noto. Route analysis by GIS and the consideration of
      population distribution and location of business establishment will be needed.

PMID- 29650868
TI  - [Present Status and Problems of Management and Guidance for Visiting Pharmacy
      Service to In-home Patients by Hospital Pharmacists].
AB  - We conducted a survey of the background of 41 patients who received management
      and guidance from an in-home visiting pharmacy service and of the contents of
      support by the pharmacist, using patients' medical records from May 2016 to March
      2017. Support comprised delivery of medicine to alleviate a burden to caregiver,
      suggesting medication, adjusting remaining medicines, and providing support
      during hospitalization. Out of 285 visits, there were 32 visits for which a
      medical fee could not be claimed. The main reasons for this were delivery of
      medicine on the day of visiting medical care, management of prescribed medicine
      at home, and delivery of temporal medicines. We used SWOT analysis to examine the
      problems and to consider improvements. The results showed that the different
      method for calculating medical fees is disadvantage for the hospital pharmacy,
      compared with the health insurance pharmacy. On the other hand, an advantage for
      the hospital pharmacist is that he or she can refer to the patient's medical
      records and support them during hospitalization.

PMID- 29650869
TI  - [Introduction of PBPM and Its Effects for a Home Care Support Clinic].
AB  - Medical teams have been promoted in home care. It is possible for pharmacists who
      are part of a multidisciplinary team to maintain safety and improve the quality
      of medical care. Protocol-based pharmacotherapy management(PBPM)is recommended
      for cooperation between the pharmacist and the doctor in the management of
      pharmacotherapy. In order to introduce PBPM, it is necessary for the pharmacist
      and the doctor to cooperate and to extract the problems in community medicine. In
      this study, the clinic pharmacist examined the problem of unnecessary inquiries
      and proposed PBPM. He suggested that to smoothly introduce PBPM, a protocol
      creation committee should be set up and an explanation of PBPM should be provided
      to the Community Pharmacist Association. As a pilot study, we created 5 protocols
      at Doctor GON Kamakura Clinic with the cooperation of 8 pharmacies. As a result,
      it became possible to reduce unnecessary inquiries by 46%. Careful coordination
      is necessary in order to introduce PBPM at clinics and community pharmacies.
      Moreover, a clinic pharmacist is able to facilitate the introduction of PBPM in
      the role of coordinator.

PMID- 29650870
TI  - [Efforts of Deprescribing Drugs and Its Achievements in Institutionalized
      Individuals].
AB  - Recently, the combined use of multiple drugs for coexisting multiple diseases in
      elderly patients has become a problem. In facilities for elderly persons,
      pharmacists contribute to the intervention and optimization of prescriptions.
      However, the procedures have been conducted smoothly in only a few facilities. We
      established five procedures for prescription intervention by pharmacists and
      implemented these interventions in 80 institutionalized individuals. The total
      results over 2 years(January 1, 2015 to December 31, 2016)revealed 118 cases of
      prescription proposals from pharmacists and a reduction of 2,411,937 yen in
      medical expense. The purpose of prescription proposals from pharmacists is to
      reduce burden on patients by optimizing prescriptions, but not to reduce the
      number or dose of drug. In doing so, it was important to hear patients' opinions
      on medical care. Patient-centered prescription proposals from pharmacists are
      considered to have improved the quality of medical care and may enable the
      promotion of prescription intervention.

PMID- 29650871
TI  - [A Discussion of Involvement of Pharmacists in Home Medical Care in Foreign
      Countries and International Comparison of Medical Care System].
AB  - In an aging society, the sustainability of the public medical system is the most
      important factor. I surveyed leading cases in Japan, as well as corresponding
      cases overseas. I also conducted interviews in Britain, North America, and
      Europe, and these indicated the current trends and issues. The UK has a universal
      insurance system and, facing a declining birthrate and an aging population, they
      have adopted a policy of immigration, which has various problems. However, the GP
      system is highly regarded by the OECD. Denmark has also introduced a similar
      medical system and they are implementing social security policies based on ICT.
      Sweden managed to cover an extreme shortage of pharmacists by adopting several
      policies. The U. S., under the pressures of their current health insurance
      system, is now shifting to preventive and early intervention by cultivating
      public consciousness in this area. In comparison, there is no country like Japan,
      which has a serious problem of an increasingly aging population, and where
      pharmacists play important roles in home care. However, leading overseas cases
      are worth learning from.

PMID- 29650872
TI  - [Examination of Patients That Died within 48 Hours after Urgent Hospitalization].
AB  - We offer inpatient support for end-stage cancer patients, not only in palliative
      care units, but also in general medical and long-term care units. We also provide
      outpatient palliative care and offer emergent backup for the regional home care
      clinics. From January 2014 to December 2016, 1,832 patients were hospitalized,
      and among them, 983 patients visited our hospital on an emergency basis. Among
      the urgent hospitalized patients, 378 patients returned home after adequate
      palliative care. But 605 patients had to stay admitted in the hospital until
      their time of death. Ninety-one patients died within 48 hours after urgent
      hospitalization. Of these 91 patients, 70% came to our hospital because of
      increasing dyspnea and decreased level of consciousness additionally, 36 of 91
      patients had received treatment by home care clinic doctors, and 50% of them had
      hoped for at-home death. The patients' preference of treatment facility tends to
      vary depending on their general condition. Hence, we have to offer appropriate
      facilities for palliative care. Building good relationships between hospitals and
      regional home care clinics and creating a system for patients to choose the
      appropriate time and place for treatment with a smooth transition from their home
      to the hospital during their end-of-life period is important in this process.

PMID- 29650873
TI  - [Examination of Home Care Patients Who Died within One Week after Hospitalization
      in the Palliative Care Unit].
AB  - Our palliative care unit(PCU)supports the home care patient through
      emergencyacceptance for 24 hours, and 26.6%of inpatients died within 1 week after
      hospitalization in 2015. We examined the background of patients who became
      hospitalized in the imminent condition of life. Symptoms of dyspnea and
      generalized weakness were causes of hospitalization even with experienced home
      medical intervention, and there was a tendencyof the rate of death within 1 week
      after hospitalization to be high. Qualityof palliative care for short-term death
      cases after PCU hospitalization is a major concern.

PMID- 29650874
TI  - [Findings from Actual Situation of Cooperation between Discharge Nurses and Home
      Visiting Nurses from Shifting to Home Care through Terminal Phase in Terminal
      Cancer Patients].
AB  - We conducted questionnaire surveys focusing on the"actual situation of
      cooperation between discharge nurses and homevisiting nurses etc. from transition
      to home-care through the terminal phase in terminal cancer patients."As a
      result,discharge nurses were employed at acute-stage hospitals to practice
      discharge adjustment. Medical staff in home care and home care workers
      continuously supported the patients and their families in managing difficulties
      such as changes in pathological conditions and care-related anxiety after the
      patient was discharged. Amidst these efforts,over 80% of home-visiting nurses
      thought that there was some disagreement about the understanding of pathological
      conditions between the hospital medical staffs and the patients/their families
      while shifting to home care(immediately after shifting to home care). It was also
      clarified that the informed consent for and instructions regarding discharge
      according to individual patients and families were insufficient.

PMID- 29650875
TI  - [Medical Home-Care Support Activities by Clinics in Japan: Developments Since
      2008].
AB  - The purpose of this study is to investigate the comparative changes over time of
      the home care supporting clinics(HCSCs) in each of the 4 Secondary Medical Areas
      within Mie Prefecture. There were 129 HCSCs activity reports in 2008, and 170 in
      2014. The number of patients and the number of deceased patients have increased
      in Mie Prefecture. These findings suggest that improvements in the home-care
      staff recruitment system should be further expanded throughout Mie Prefecture
      and, in particular, the quality improved in the Higashi-Kishu area.

PMID- 29650876
TI  - [Home Medical Care Promotion for Multidisciplinary Cooperation].
AB  - It may be said that the effective functioning of an integrated community care
      system depends entirely on home medical care. "Cooperation"is necessary in
      pushing home medical care forward and it is vital to advance as a system. In
      Iwaki-city, the municipal government and the medical association have been
      sponsoring many types of multidisciplinary cooperation workshops for home medical
      care promotion. There was administrative participation, and cooperation became
      the main workshop focus. We hold workshops 2 times a year. The Iwaki City Medical
      Association holds lectures on home medical care in the town. Doctors who work in
      medical offices and hospitals attend the lectures, with topics such as family
      medicine, understanding dementia, advice for the acceptance of medical
      examination, cancer screening in the local community hall, and gaining a
      favorable reception. In our hospital, I hold many types of workshops on home
      medical care in southern Iwaki-city and on facilitating cooperation. These
      contribute to collaboration, as they facilitate face-to-face interaction in an
      important area. I also report the actions taken in our hospital.

PMID- 29650877
TI  - [Activity Report and Future Prospects of the Medical and Nursing Care Cooperation
      Desk in Koshigaya City].
AB  - The "medical and nursing care cooperation desk" was established within the
      Koshigaya Medical Association in April 2016 in and began operating in Koshigaya
      City. There were 243 consultation cases during the 17 months from April 1, 2016
      to August 31, 2017. Consultation with medical institutions and visiting nursing
      stations accounted for 42%of cases and nursing-related personnel accounted for
      40%. Regarding consultation contents, transition to home medical care accounted
      for 50%of cases. We publish a monthly information magazine, "Cooperation Between
      Medical Care and Nursing Care,"with information on the contents of consultation,
      and multidisciplinary information sharing is being planned. Moreover, we hold
      training sessions and raise awareness in order to establish positive
      collaboration between medical care and nursing care. The role of the cooperation
      desk is not only related to the discharge of hospitalized patients, but is also
      widely involved in structuring community- based integrated care systems.

PMID- 29650878
TI  - [Balance in Disaster Preparedness between Public, Self-, and Mutual Help for Home
      Cared Individuals].
AB  - At present, when it is predicted that large-scale disasters may occur, repletion
      and reinforcement of disaster preparedness are required. For disaster
      preparedness, a balance between public, self-, and mutual help is important.
      However, designated hospitals and their support systems were placed importance in
      medical care during disasters, and preparedness in regard to home care has not
      been discussed sufficiently. The purpose of this study is to clarify preparations
      that home-visit nursing stations may implement, states of support for self-help
      of cared persons and their families and mutual help such as of communities, in
      home-visit nursing stations in the areas where large-scale damages by Tokyo
      Inland Earthquake and Nankai Trough Earthquake are assumed. We found that
      although the preparation of home-visit nursing stations has been progressive, the
      supports for self-help of cared persons and their families and for mutual help
      such as that involving communities have been insufficient. The findings indicated
      that a balance in preparedness has not been achieved thus far. From this study,
      we could obtain useful documents to enrich and reinforce future preparations.

PMID- 29650879
TI  - [A Study on Designs and Achievements of Trainings for Enhancing the Self-Help
      Ability of Home-Cared Persons in Preparing for Disasters - Review of Disaster
      Drills with Cared Persons and Their Families].
AB  - After the Great East Japan Earthquake, we re-recognized the importance of self
      help efforts of home-cared persons and their families and the necessity of
      advanced measures. In 2013, we designed a disaster drill to enhance the self-help
      ability of home-cared persons and their families in a stepwise fashion. In 2016,
      for the purpose of reviewing the achievements of the designed drill and its
      contents, the disaster drill was conducted on 21 users of our home-visit nursing
      station, followed by a questionnaire survey regarding the training contents,
      date/time, documents used, change in awareness, disaster-preventive actions, etc.
      The training date and time was evaluated to be"good"by all the subjects, with the
      required time and the documents used also considered to be"appropriate"(95.2%).
      The participants answered"greatly improved"or"rather improved"with regard
      to"change in awareness"(85.7%). Disaster-preventive actions included"inspection
      and purchasing of emergency supplies"(38.1%),"reconfirmation of the
      manual"(19.0%), etc. The free description included"feeling of security due to the
      training,""enhanced disaster-preventive awareness,"etc. The above findings
      indicated that the contents designed were generally supported and received
      recognition, while post training, participants' disaster-preventive awareness and
      the self-help ability of the home-cared persons and their families were enhanced,
      as analyzed by their free descriptions.

PMID- 29650880
TI  - [Team Collaboration in Home Medical Care to Support Patients at the End-of-Life -
      Review of Service Personnel Meeting on Discharge Day].
AB  - Due to the rising number of patients at the terminal stage or with high
      dependence on medical care, the cooperation of 2 teams, the hospital discharge
      support team and the home support team, has become very important. The recent
      spread of the Internet has enabled both patients and their families who have
      chosen home care to obtain a wide range of information about home services, as
      well as diseases, and form a picture of what will happen. However, there are
      actually many cases in which patients and families find that things are not as
      they imagined, and they are uneasy and unsure of what to do. Here, we report a
      case in which the mismatch between the patient's and family's expectations
      created an unsatisfactory care situation.

PMID- 29650881
TI  - [Combination Therapy of Oxycodone and Tapentadol Was Effective for Intractable
      Pain Caused by Breast Cancer Bone Metastasis - A Case Report].
AB  - A 52-year-old woman had been prescribed oral medication of acetaminophen, non
      steroidal anti-inflammatory drugs (NSAIDs), and oxycodone for intractable pain
      associated with thoracic metastasis of breast cancer. However, the pain control
      was poor. Although pregabalin and gabapentin were used as supplementary
      analgesics, they could not be continued because of their side effects. Based on
      the noradrenalin reincorporation-inhibiting action of tapentadol, a combination
      therapy of tapentadol and oxycodone was introduced and satisfactory pain control
      was achieved. No side effects from the combined opioids were observed. This
      finding indicates the potential of administrating a combination therapy of m
      opioid receptor agonists(such as morphine, oxycodone, and fentanyl)with
      tapentadol, which has a noradrenaline reincorporation-inhibiting action, as an
      effective remedy for alleviating intractable pain complicated with neuropathic
      pain.

PMID- 29650882
TI  - [A Study of Sustainable End-of-Life Care in a Depopulating Society].
AB  - In facing a society characterized by a decreasing population, I think that
      sustainability of end-of-life medical care needs to prevent death in isolation,
      offer optimal allocation of medical care providers, and ensure the centralization
      of urban functions. How do leading practitioners who actually practice advanced
      medical care view my hypotheses ?My survey showed that my hypotheses turned out
      to be unsupported, but on the other hand, it also indicated the concerns and
      resolve of leading medical practitioners and their views on venturing into
      unknown domains.

PMID- 29650883
TI  - [Cancer Disease Trajectory and the Contribution of Artistic Outreach Activity to
      Palliative Care].
AB  - The purpose of this article is to show some unintentional aspects of palliative
      supports offered by the community. The activities of the Opera Ehime, an amateur
      opera group, play an important role in palliative and grief care. This community
      is also committed to providing supportive care for home hospice cancer patients
      through an outreach music program that offers patients connection with others and
      reduces isolation. Assessment by the coordinator includes determiningthe
      patients' preferences and the relevance of music throughout their lives. Then,
      the coordinator predicts the cancer trajectory and invites patients to
      participate in the home hospice concert at any stage of their illness. These
      activities are an effective form of supportingcancer care for patients to promote
      wellness and improve physical and emotional well-being, as well as quality of
      life.

PMID- 29650884
TI  - [Role of Pharmacists in the Care of Pediatric Patients Needing Home Visiting
      Intervention for Pharmaceutical Management and Their Life Depending on Medical
      Care].
AB  - Medical advances have made it possible to save lives of children with severe
      refractory diseases. As a result, the number of children who need continuous
      medical care at home has increased. However, currently, few medical personnel of
      both medical institutions and pharmacies are aware of home visiting intervention
      for pharmaceutical management. Home visiting intervention should be utilized more
      for severely impaired children who are highly dependent on medical care to
      effectively reduce the nursing care burden of the family and to secure
      pharmaceutical supply path.

PMID- 29650885
TI  - [Fentanyl Citrate Sublingual Tablets Were Effective in Relieving Symptoms of
      Akathisia - A Case Report].
AB  - Akathisia is a condition wherein sitting calmly and quietly is impossible, with a
      representative complaint of restless legs. It is generally assumed to be caused
      by anti-dopamine activity. In severe cases, it has been known to result in
      suicide attempt. We reported a case of drug-induced akathisia with difficulty in
      oral intake, in which fentanyl citrate sublingual tablets were found to be
      effective in relieving symptoms. The patient was a female aged 50's who had a
      gastric cancer with peritoneal dissemination causing pain and vomiting.
      Palliative care was requested for management of symptoms. Metoclopramide and
      haloperidol were administered for vomiting. However, because of the complaints of
      restless legs, the case was diagnosed as drug-induced akathisia. Fentanyl citrate
      sublingual tablets were then administered for pain management, resulting in
      temporary improvement of akathisia symptoms.

PMID- 29650886
TI  - [Usefulness of Suvorexant for Complicated Delirium in Cancer Patients Who
      Experience Sleep Disturbance during Hospitalization].
AB  - We investigated the usefulness of suvorexant for complicated delirium in patients
      with cancer who experience sleep disturbance during hospitalization. Nine
      patients with malignant tumors complicated with symptoms of delirium and insomnia
      were included in this study; their palliative care was managed by the palliative
      care team of our hospital for a period of one year from April 2016 to March 2017.
      A retrospective follow-up study was then conducted. The Japanese version of DRS
      R98 was used to evaluate the severity of the patient's delirium. The total
      severity score of DRS-R98 significantly decreased after the administration of
      suvorexant when compared to the score before its administration(6.66+/-1.73 vs
      10+/-3.20, p=0.0031). In addition, suvorexant did not exhibit any harmful
      effects. Our results indicate that suvorexant was useful in alleviating delirium
      symptoms in cancer patients who experience sleep disturbance.

PMID- 29650887
TI  - [Assessing Patient Factors Influencing the Discontinuation of Opioids after Intra
      Arterial Chemotherapy for Oral Cancer - A Retrospective Study].
AB  - Superselective intra-arterial chemoradiation therapy for oral cancer induces the
      complication of mucositis. Although the associated pain is controlled using
      opioids, major questions from patients in clinical practice are as follows:(1)the
      mean number of days from the completion of superselective intra-arterial
      chemoradiation therapy to the discontinuation of opioid administration,
      and(2)patient factors enabling the discontinuation of opioids. The purpose of
      this study was to clarify these points. A retrospective follow-up study was
      conducted from April 2016 to March 2017 on patients who underwent superselective
      intra-arterial chemoradiation therapy at our department of oral surgery. The
      patients were divided into 2 groups:one who discontinued opioids, and the other
      who did not. Clinical backgrounds and data were compared between the 2 groups.
      The mean number of days from the completion of superselective intra-arterial
      chemoradiation therapy to the discontinuation of opioid administration was 51+/
      34.4 days. The absence of diabetes and deliria during treatment were determined
      as factors contributing to the discontinuation of opioids.

PMID- 29650888
TI  - [Actual Situation and Subjects in Calculations of Cancer-Patients
      Instruction/Management fee 2 at Hospital A - Focusing on Home-Cared Patient's
      Discomfort and Thoughts].
AB  - Since 2010, Cancer-Patient Instruction and Management fees has been included in
      remuneration for medical services.At Hospital A, calculation of the Cancer
      Patient Instruction and Management fees 1 and 2 was started in 2016. Since then,
      2 years have passed.Interview contents of the Cancer-Patient Instruction and
      Management fee 2, which nurses have calculated, were reviewed and home care
      patient's discomfort during and thoughts about anti-cancer drug treatments were
      clarified. The contents of interviews were coded and analyzed.It was found that
      outpatients receiving anti-cancer drug treatment had faced the deaths of their
      fellow patients with the same disease, discovered the meaning of life and sense
      of self in struggle with the disease that is uncertain about the future, and
      continued the treatments to sustain life while taking their families into
      consideration.

PMID- 29650889
TI  - [Relationship between Nutritional Biochemical Parameters and Body Weight Loss in
      Patients with Esophageal Cancer Up to One Year after Surgery].
AB  - SUBJECTS AND METHODS: The subjects comprised 21 patients with esophageal cancer
      who underwent surgery, without adjuvant chemotherapy. Caloric intake, body weight
      loss, and biochemical parameters(serum albumin[Alb], hemoglobin[Hb],
      transthyretin[TTR], and total cholesterol[T-Cho])were measured up to 1 year after
      surgery, and relationships between all parameters were investigated. RESULTS: The
      caloric intake dropped to about 87% of base-line intake at 1 month after surgery
      and recovered to 100% at 1 year after the operation. Body weight also dropped to
      about 89% of baseline at 6 months after surgery and then was relatively stable.
      Caloric intake was significantly positively correlated with TTR(r=0.82, p=0.02),
      and it also tended to be positively correlated with T-Cho(r=0.70, p=0.14). Body
      weight loss was significantly negatively correlated with Alb(r=-0.82, p=0.01)and
      Hb(r=-0.87, p=0.01). CONCLUSION: Alb and Hb were recovered in the early
      postoperative period when body weight was still decreased. However, TTR appeared
      to be a good parameter of caloric intake in the short-term, postoperatively.

PMID- 29650890
TI  - [Patient Factors Enabling the Decannulation of the Gastrostomy Tube after
      Superselective Intra-Arterial Chemoradiation Therapy for Locally Advanced Oral
      Cancer - A Retrospective Study].
AB  - Superselective intra-arterial chemoradiation therapy for locally advanced oral
      cancer induces complications such as mucositis, which impedes oral intake. Thus,
      at our hospital, a gastrostomy is performed in almost all patients during the
      treatment period to ensure the presence of an alternative administration route
      for nutrition and drugs. The purpose of this study was to calculate the mean
      number of days from completion of superselective intra-arterial chemoradiation
      therapy to the decannulation of gastrostomy, and extract patient factors for the
      decannulation. A retrospective follow-up study was conducted from April 2016 to
      March 2017 on patients who underwent superselective intra-arterial chemoradiation
      therapy at our department of oral surgery. The patients were divided into 2
      groups:one who was decannulated and the other who did not. Clinical backgrounds
      and data were compared between the 2 groups. In the group with the decannulation,
      the mean period from treatment completion to the decannulation was 132+/-51.6
      days. Heavy alcohol consumption, absence of haphalgesia before treatment, and
      possible securement of the opening with the breadth of 3 fingers, were determined
      as factors contributing to the decannulation of gastrostomy tube.

PMID- 29650891
TI  - [Fourteen Cases of Implanted Central Venous Access Port-Related Bloodstream
      Infection].
AB  - We conducted a clinical study involving cases of central venous(CV)port-related
      infection in Tokyo Rosai Hospital. Fourteen patients with suspected CV port
      related infection at Tokyo Rosai Hospital between April 2015 and January 2017
      were observed. Identical bacterial types were detected from 2 sets of blood
      cultures and cultures from the catheter tip, and a definitive diagnosis was made.
      Data on patient background, causative bacteria, quick sequentialorgan failure
      assessment (qSOFA)score, CV port placement period, presence or absence of local
      inflammatory findings, and prognosis were analysed. The causative bacteria were
      coagulase-negative Staphylococcus(CNS)in 7 cases(50%), Staphylococcus aureus in
      3(21%), and Candida in 4(29%). Most CNS-infected cases(71%)exhibited a qSOFA
      score of 1 or less at the examination time, which indicated that even if
      bacteremia occurred in CNS cases, organopathy might not occur easily. Local
      inflammatory findings were found in only 3 CNS cases. Cases without local
      inflammatory findings showed methicillin-resistant Staphylococcus
      aureus(MRSA)(18%)or Candida(36%)at high proportions, indicating that treatments
      might be difficult.

PMID- 29650892
TI  - [Continuous Subcutaneous Injection Therapy in End-of-Life Symptoms of Cancer and
      Non-Cancer Patients].
AB  - The significance of continuous subcutaneous injection(CSI)therapy was assessed in
      end-of-life symptoms of cancer and non-cancer home hospice patients. In a
      retrospective analysis of 106 advanced cancer patients who underwent opioid CSI
      therapy, the most frequent symptom was pain(65%), followed by dyspnea(46%),
      seizure(8%), ileus(8%), and other uncontrolled end-of-life symptoms(23%). The
      median oral morphine equivalent daily opioid dose was 90 mg(2.5-1,920 mg)and the
      median duration of CSI administration was 3 days(1-350 days). Eighty-six percent
      of the patients underwent adjunct therapy to opioids, such as midazolam,
      octreotide, and haloperidol, in the management of cancer pain and non-pain cancer
      symptoms. In 5 non-cancer patients with systemic vascular disease, various
      symptoms required opioid CSI in the endof- life days. CSI with adjunct therapy to
      opioids can be effective in the treatment of end-of-life symptoms in both cancer
      and non-cancer patients.

PMID- 29650893
TI  - [Towards Development of Innovative Cancer Therapies - Trans-OMICS Approach].
AB  - Comprehensive genomic and transcriptome analyses using next-generation
      sequencing(NGS)analysis has lead a discovery of a variety of novel driver gene
      mutations and new therapeutic targets for cancer patients, and has remarkably
      improved outcome of the patients through the development novel molecular
      targeting drugs. Even so, in so-called intractable or refractory cancers, those
      "druggable"alterations common to the diseases are rarely found due to the high
      diversity of the tumor. Furthermore, most of molecular target therapy is known to
      acquire the resistance to the drug by means of multiple factors such as up
      regulation of the partially inhibited pathway, mutation of the target, activation
      of alternative pathways, histological translocation, and oncogene de-addiction.
      Understanding of intra-tumoral heterogeneity and tumor-stromal crosstalk in tumor
      microenvironment with consequence of biological network re-construction are also
      of key importance to overcome the resistance. These suggest the limitation of
      mono-layer OMIC approach focusing on genome and/or cancer cell alone to identify
      truly effective therapeutic target and biomarker. Under these
      circumstances,"Trans-OMICS" concept has emerged as a novel approach to clarify a
      global biochemical network across multiple omics layers(eg genome, transcriptome,
      proteome, and metabolome)directly correct with a variable phenotype by use of
      both multi-omic measurements and computational data integration. This approach
      has great potential for drug discovery and clinical implementation of omics-based
      cancer medicine. We introduce here the outline of technologies and analysis for
      Trans-OMICS approach, and review for the recent studies in oncology research with
      showing our recent attempt.

PMID- 29650894
TI  - [Chemoradiotherapy, the Standard Treatment at Present].
AB  - Chemotherapy concurrent with radiotherapy has been widely used in clinical
      practice because the additional benefit on radiotherapy alone had shown. Head and
      neck cancer: CDDP concurrent with radiotherapy has been a standard treatment for
      15years both in definitive setting and postoperative setting. Esophageal cancer:
      5-FU/CDDP is the best partner for radiotherapy and appropriate radiation dose has
      been discussed. Anal cancer: Radical concurrent chemoradiotherapy with 5-FU and
      mitomycin C(MMC)remains the standard of care for squamous cell carcinoma of the
      anus. Recent radiotherapy techniques can realize decreasing radiation doses to
      the organs at risk and ensuring a shorter overall treatment time without the need
      for treatment breaks. In medical oncology field, some molecular targeting agents
      containing regimens had been standard treatments instead of conventional
      therapies from 2000. However, there are a few regimens which can change the
      standard in combination with radiotherapy at this point. We hope new regimens
      with radiotherapy will emerge and replace the conventional standard in near
      future.

PMID- 29650895
TI  - [Chemoradiotherapy Using Molecular Targeted Therapy].
AB  - Instead of the combination treatment with cytotoxic chemotherapy and radiation
      therapy, molecular targeted drugs is testing in many clinical trials. Because
      unexpected adverse events were reported in the previous trials using molecular
      targeted drugs with radiotherapy, attention should be paid to this combination.
      In EGFR mutated lung cancer, gefitinib with radiotherapy is testing.

PMID- 29650896
TI  - [The Combination of Molecular Targeted Agents with Radiotherapy in Head and Neck
      Cancer].
AB  - Concurrent cisplatin based chemoradiotherapy(CRT)is the standard of care for
      patients with locoregionally advanced squamous cell carcinoma of the head and
      neck(LA-SCCHN). Based on the Bonner trial showing the superiority of cetuximab
      plus radiotherapy to radiotherapy alone, cetuximab based bioradiotherapy(BRT)is
      considered as an alternative for patients with LA-SCCHN. However, the non
      inferiority of BRT compared to CRT has not yet been demonstrated. Furthermore,
      severe mucositis and dermatitis induced by BRT cannot be neglected. Therefore,
      the patient's general status and comorbidity should be considered before BRT.
      Supportive care and patient education are also necessary to safely complete the
      treatment. Several phase III trials are ongoing to evaluate BRT and CRT for human
      papillomavirus(HPV)positive oropharyngeal carcinoma. Novel biomarkers are needed
      for identifying patients most likely to benefit from BRT.

PMID- 29650897
TI  - [Radiotherapy and New Cancer Drugs - New Side Effects ?]
AB  - Chemotherapeutic agents(cytotoxic anticancer drugs)have played a central role as
      cancer drug therapy for a long time. Since the 2000s, molecular targeted drugs
      have been developed as therapeutic methods that match the standards specifically
      for cancer cells, and in solid cancers epidermal growth factor receptor(EGFR)and
      vascular endothelial growth factor(VEGF) have been approved mainly for drugs
      targeted. The combination therapy of molecular targeted drugs and radiotherapy
      has been developed to solve the problem of many adverse events of chemo
      radiotherapy. However, cetuximab-combined radiotherapy, which is a typical
      combination therapy, is not a treatment with few adverse events, centered on
      acute dermatitis and mucositis, it is important to properly select cases.
      Similarly, it is necessary to pay attention to specific gastrointestinal
      obstruction in combination treatment of angiogenesis inhibitor and radiotherapy.
      In recent years, immune checkpoint inhibitors also have been focused on many
      cancers and attract attention. To achieve further efficacy, combination therapy
      with radiotherapy are testing.

PMID- 29650898
TI  - [Musculoskeletal Tumor Adjuvant Chemotherapy for Malignant Bone and Soft Tissue
      Tumors].

PMID- 29650899
TI  - [I. Adjuvant Chemotherapy for Sarcoma of Bone].

PMID- 29650900
TI  - [II. Perioperative Chemotherapy for Adult Soft Tissue Sarcomas].

PMID- 29650901
TI  - [III. Adjuvant Chemotherapy for Pediatric Sarcoma].

PMID- 29650902
TI  - [The Significance of Pharmacist Intervention Focused on Improvement of Adverse
      Events and Cancer Pain].
AB  - It was reported that focusing on palliative care for patients with cancer
      improved their anxiety and depression and prolonged their survival. Similarly,
      the pharmacist intervention for cancer patients suggested the improvement in
      anxiety and depression; but, such improvement has not yet been demonstrated by
      focusing on pharmacist attitudes and behaviors of which the patients were the
      primary beneficiaries. Therefore, we evaluated the significance of pharmacist
      intervention focusing on improvement of adverse events and cancer pain. We
      randomized patients to pharmacist intervention group or no intervention group and
      evaluated whether the pharmacist intervention improved patients' anxiety and
      depression. Patients receiving new chemotherapy in the outpatient chemotherapy
      room were invited to enroll in this study between July 2015 and February 2017.
      The patients were assessed for their quality of life using the Structured
      Clinical Interview for ACD and for anxiety and depression using the Structured
      Clinical Interview for HAD at baseline and again at the 4th chemotherapy. The
      difference between the baseline and 4th chemotherapy scores was calculated and
      compared between the pharmacist intervention and no intervention groups. HAD
      depression subscale and HAD scale scores decreased in the pharmacist intervention
      group compared to the no intervention group,(-1 versus 0.5, p=0.024)and(-3 versus
      0.5, p=0.011)respectively. We demonstrated that the pharmacist intervention
      focused on improvement of adverse event and cancer pain decreased cancer
      patients' anxiety and depression.

PMID- 29650903
TI  - [Diffuse Malignant Peritoneal Mesothelioma with Secondary Liver Invasion
      Diagnosed Using Laparoscopy - A Case Report].
AB  - A 69-year-old man with right upper quadrant abdominal pain and fever was referred
      to our hospital. He had a history of asbestosis exposure. Computed
      tomography(CT)revealed a mass at the right subhepatic space, and an antibiotic
      was administered after a diagnosis of an abdominal abscess. However, the patient
      did not respond to the treatment, and finally, exploratory laparoscopy was
      performed. A sheet of combined white nodules surrounding the right lobe of the
      liver was found, and the mass was continuous with the covering particles. Biopsy
      of the mass and immunohistochemical examination was performed. The resulting
      diagnosis was diffuse epithelial malignant peritoneal mesothelioma(MPM).
      Postoperative systematic chemotherapy of pemetrexed and cisplatin was
      administered. Laparoscopy was useful to evaluate the distribution of the MPM,
      which led to adequate therapeutic determination.

PMID- 29650904
TI  - [A Case of Resected Esophageal Endocrine Cell Carcinoma That Responded to
      Combination Therapy Comprising Irinotecan and Cisplatin].
AB  - We report a case of resected esophagealcancer that responded wellto first-line
      combination therapy comprising irinotecan and cisplatin. The patient was a 71
      year-old woman being treated for liver cirrhosis. She was admitted to our
      hospital in April 2015 because of dysphasia. Endoscopic examination revealed a
      tumor in the mid-thoracic esophagus, which was diagnosed as an endocrine cell
      carcinoma following pathological examination. Contrast-enhanced computed
      tomography and positron emission tomography did not show lymph node or distant
      metastases. She was treated with irinotecan and cisplatin combination therapy.
      After 6 courses of treatment, the tumor size had remarkably reduced.
      Subsequently, we performed subtotal esophagectomy and gastric tube reconstruction
      through the retroposterior mediastinalroute and the histologicaleffect was
      reported as a partial response. No viable tumor cells were observed in the
      extracted lymph nodes. However, bone metastasis and lymph node swelling occurred
      after 4 months. She received other therapeutic regimens, such as etoposide and
      carboplatin combination therapy. However, the tumor gradually progressed, and she
      died 18 months after the first treatment. Irinotecan and cisplatin combination
      therapy is a possible option for the management of esophageal endocrine cell
      carcinoma as a first-line treatment.

PMID- 29650905
TI  - [A Case of HER2-Positive Breast Cancer with Liver Metastases Showing Three Years
      of Complete Response to Combination Therapy with Trastuzumabplus Pertuzumab].
AB  - A 48-year-old woman with severe interstitial pneumonitis was diagnosed with right
      breast cancer(invasive ductal carcinoma, T1aN1M0, ER+, PgR-, HER2 3+)and
      underwent modified radical mastectomy.The patient was administered tamoxifen as
      adjuvant therapy.However, 1 year after the mastectomy, multiple liver metastases
      were found and the patient received 2 anti-HER2 agents, trastuzumab and
      pertuzumab.A complete response(CR)was observed with the disappearance of the
      liver metastases in 7 months.CR was maintained for 2 years after the initiation
      of treatment, and then, we started trastuzumab monotherapy, which has resulted in
      long-term disease control.

PMID- 29650906
TI  - [A Case of Stage IV Gastric Cancer Curative Resection by Conversion Therapy].
AB  - We experienced a case of curative resection as a multidisciplinary treatment for
      unresectable gastric cancer that attributed to peritoneal disseminations and
      direct invasion to other organs.Two courses of triplet chemotherapy(DCS
      therapy)were performed under enteral stent placement and nasoenteral nutrition
      for direct infiltration into the transverse colon with entire circumference
      stenosis.Distal gastrectomy and right hemicolectomy were performed as conversion
      therapy, and R0 resection was achieved.After the operation, S-1 as adjuvant
      chemotherapy was performed and there has been no relapse survival for 13 months
      since the operation.From this case, it seems that conversion therapy plays an
      important role in prognosis extension as a treatment strategy for Stage IV
      gastric cancer.

PMID- 29650907
TI  - [Cases of Oncologic Emergency Associated with Colorectal Cancer].
AB  - The clinical condition of oncologic emergency associated with colorectal cancer
      includes hemorrhage, perforation and obstruction. Obstructive colorectal cancer
      is an oncologic emergency commonly observed in our daily clinical practice.
      Colonic stent placement for obstructive colorectal cancer is relatively easy and
      safe and may be considered as an effective treatment method that enables
      favorable intestinal decompression preoperatively and one-stage resection.
      Colonic stent use can be a bridge to surgery, enabling shorter duration of
      hospitalization, and reduced postoperative complications, and colostomy rates, as
      compared to emergency surgery. From January 2009 to December 2016, this study was
      designed to evaluate the clinical outcomes of 68 patients who underwent surgery
      for obstructive colorectal cancer. The patients were divided into 2 groups: 32
      cases receiving colonic stent placement(the S group), 36 cases receiving ileus
      tube and emergency surgery(the NS group). There was no significant difference in
      terms of morbidity or survival rate between the 2 groups. For the S group, 31 out
      of 32 could one-stage resection(94%). The colostomy rate in the S group was
      significantly lower than that in the NS group(3% vs 33%). In the S group, number
      of dissected lymph nodes was significantly larger and the duration of
      postoperative stay was shorter than that in the NS Group.

PMID- 29650908
TI  - [Advanced Gastric Cancer with Peritoneal Dissemination Treated with Conversion
      Surgery after S-1 and CDDP Chemotherapy - A Case Report].
AB  - A 27-year-old woman was diagnosed with gastric cancer complicated peritoneal
      dissemination and direct invasion to pancreas via staging laparoscopy. After
      systemic chemotherapy using regimen of S-1/CDDP for 2courses, the tumor did not
      increase in size and peritoneal dissemination did not progress. The patient
      subsequently underwent distal gastrectomy as a curative surgery. The histological
      diagnosis was ypT4bN1M0, ypStage III B. The patient was treated with DOC/CDDP for
      6 courses after surgery as adjuvant therapy. At present 6 years after surgery,
      the patient is alive without tumor recurrence.

PMID- 29650909
TI  - [Endoscopic Topical Therapy Using Mesh for Refractory Suture Failure after Rectal
      Cancer Surgery].
AB  - We reported a case that could be cured with endoscopic topical therapyusing mesh
      for refractorysuture failure after rectal cancer surgery. The patient was a 73
      year-old man. He was diagnosed as lower rectal cancer, and underwent laparoscopic
      super law anterior rectum resection. On the 13th postoperative day, abdominal
      pain appeared, suspected ileal necrosis, emergencylaparoscopic examination
      laparotomywas performed. Upper gastrointestinal perforation was suspected from
      pus and food on the whole intraperitoneal cavity, and we moved laparotomy. But
      any perforations were not found, we resected ileum and inserted a drain tube to
      Douglas fossa. After second surgerydischarge of the juice from the drain was
      confirmed, diagnosis was made of suture failure of the anastomosis of the rectal
      cancer. He rejected artificial stomy, we chose conservative therapy. On 114th day
      after second surgerywe put a mesh for inguinal hernia in the puncture under the
      endoscope. On the next dayafter the treatment discharge of the juice from the
      drain was stopped. And finallyhe was discharged. This endoscopic treatment is
      considered to be useful for refractorysuture failure.

PMID- 29650910
TI  - [The Actual State of Treatment of Gastrointestinal Cancer with Abdominal Aortic
      Aneurysm in Our Department over the Past Five Years].
AB  - With the aging of the population of Japan and Westernization of the dietary life,
      the number of cases in which cardiovascular diseases are merged in non-cardiac
      surgery is increasing year by year.Many of the abdominal aortic aneurysms are
      asymptomatic and it is not uncommon to be discovered accidentally in preoperative
      examination of non-cardiac surgery.When gastrointestinal surgery involves
      malignant diseases of the gastrointestinal tract and abdominal aortic aneurysm,
      the two life prognosis-related diseases are merged, depending on the severity and
      urgency of the disease for each case, its treatment to determine the priority
      order.Abdominal aortic aneurysm occurred at the time of malignant disease surgery
      in 14 cases of gastrointestinal cancer patients who underwent surgery at the
      department during the 5 years from 2012 to 2016.T he actual condition of
      treatment for these cases was investigated.

PMID- 29650911
TI  - [A Case of Advanced Gastric Cancer with Multiple Liver Metastases Treated with
      Curative Conversion Therapy after S-1 plus CDDP].
AB  - A57 -year-old man was diagnosed with advanced gastric
      cancer(adenocarcinoma[tub2/por1])with multiple(S3, S4, S5, S6, S8)liver and para
      aortic lymph node metastases. The tumor was classified as cT4a, N3, M1, HEP,
      cStage IV, and the patient received chemotherapy with S-1 plus CDDP(SP). After 10
      courses of SP, a CT scan revealed that the primary tumor and the metastases
      disappeared. The patient presented with cCR and underwent distal gastrectomy, D2
      lymph node dissection, partial hepatic resection, and cholecystectomy. The
      histological diagnosis was classified as ypT0N0M0,(ypStage 0), pCR, and
      pathological Grade 3.

PMID- 29650912
TI  - [Two Cases of Neuroendocrine Carcinoma of the Non-Ampullary Duodenum].
AB  - Here we report 2 cases of neuroendocrine carcinoma(NEC)of the non-ampullary
      duodenum which is extremely rare neoplasm. Case 1: A 76-year-old man had a type 2
      duodenal carcinoma with a 3 cm-sized lymph node metastasis. Duodenal resection
      with subpyloric lymph nodes dissection and Roux-en-Y reconstruction were
      performed. The histopathological diagnosis was NEC of the duodenal bulb after
      surgery(pT3pN1M0, stage III A, UICC 7th edition). The patient died of chronic
      heart failure 10 years and 3 months after the surgery. Case 2: A 45-year-old
      woman had a type 2 duodenal NEC of the second part of the duodenum. A subtotal
      stomach-preserving pancreatoduodenectomy was performed with lymph node
      dissection.(pT4pN0M0, stage II B, UICC 7th edition). The patient died of
      recurrence 7 months after the surgery.

PMID- 29650913
TI  - [A Case of Laparoscopic Hartmann's Operation for Perforation of Rectal Cancer in
      Superior Elderly People].
AB  - We report a case where home discharge was possible after laparoscopic Hartmann's
      operation for superior elderly perforation of rectal cancer. The patient was 91
      year-old, a woman. She was delivered to the emergency room complaining of
      weakness. We diagnosed rectal perforation and started emergency laparoscopic
      surgery. Rectal cancer perforation was observed during surgery and laparoscopic
      Hartmann's operation plus D2 lymph node dissection was performed. The operation
      time was 3 hours 21 minutes, the blood loss was 10 g. She resumed her meal intake
      from the postoperative day(POD)5 and became ready for discharge on POD 20
      postoperatively. She moved to a comprehensive care ward and she was discharged to
      her house on POD 89. On POD 120, she visited the hospital complaining of anorexia
      and anal bleeding, and was diagnosed as local recurrence in the pelvis, multiple
      liver metastases, and cancerous peritonitis. She was admitted to palliative care
      unit on POD 132 and died on POD 141. It was suggested that laparoscopic surgery
      will be minimally invasive even at superior elderly patients and that they will
      be able to discharge from their homes.

PMID- 29650914
TI  - [Surgical Procedure of Buccal Mucosal Carcinoma - Reconstruction of Mouth Angle].
AB  - Surgical resection of the buccal mucosal carcinoma often induces soft tissue
      defect. The treatment plan should be considered to preserve oro-facial function
      and morpho-esthetics. This retrospective study reports the surgical
      reconstruction procedures in buccal mucosal carcinoma patients. We evaluated 4
      cases(2 men, 2 women, mean age: 81.8 year-old)treated in Department of Oral and
      Maxillofacial Surgery, Shimane University Hospital between June 2007 and January
      2017. The average size of primary tumor was 4.9 cm2. And the average size of
      facial skin defect in the mouth angle was 3.1 cm2. The facial local skin flaps
      and/or other pedicled flap were used for the reconstruction of the mouth angle.
      Severe contraction of the scar was manifested in 2 cases. Though reconstruction
      using the local pedicled flaps for full thickness skin defect in the mouth angle
      would be feasible, special attention is considered regarding the postoperative
      contraction of the scar.

PMID- 29650915
TI  - [A Case of Primary Duodenal Cancer with Duodenocolic Fistula Treated with
      Pancreatoduodenectomy and Right Hemicolectomy].
AB  - A patient was 59-year-old female. She presented our hospital with weight loss,
      anorexia and lower abdominal bloating. Abdominal computed tomography(CT),
      gastrointestinal endoscopy, colonoscopy and duodenal fistulagram showed duodenal
      cancer or colon cancer with duodenocolic fistula and ovary metastasis. She
      underwent subtotal stomach preserving pancreatoduodenectomy and right
      hemicolectomy. In these pathological findings, tumor was diagnosed as a duodenal
      cancer with duodenocolic fistula. She was surviving 12 months after the last
      surgery. In cases of cancer with duodenocolic fistula, pancreatoduodenectomy with
      right hemicolectomy would be necessary for nutrition improvement and cancer
      treatment.

PMID- 29650916
TI  - [A Case of Sigmoid Colon Cancer with Idiopathic Thrombocytopenic Purpura].
AB  - An 80-year-old man reported at our hospital with the chiefcomplaint
      ofconstipation. He was diagnosed with sigmoid colon cancer(T4aN0M0, Stage II). He
      also had steroid-resistant idiopathic thrombocytopenic purpura(ITP)since 2001.
      After a high dose g-globulin therapy, he underwent sigmoidectomy and splenectomy
      simultaneously because ofthe steroidresistant ITP. While some reports suggest
      that ITP is dominant when it occurs with blood cancer, others suggest that it can
      be immunologically dominant even when it occurs with solid tumors. ITP has a
      significant effect on solid tumors.

PMID- 29650917
TI  - [A Case of Primary Spinddle Cell Carcinoma of the Breast].
AB  - A 76-year-old female underwent breast-conserving surgery of the right breast and
      sentinel lymph node biopsy for primary breast cancer. Three years later,
      mammography and ultrasonography showed a small nodule in the right breast. There
      was nothing abnormal in the left breast. Three months later, she complained of a
      huge and rapid growing mass in the left breast. Malignant cells were obtained on
      fine needle aspiration biopsy in the right breast tumor. But it was not possible
      to diagnose whether the left breast tumor was benign or malignant on fine needle
      aspiration biopsy and needle biopsy. Bilateral mastectomy and sentinel lymph node
      biopsy of the right side were performed. Pathological diagnosis were squamous
      cell carcinoma of the right breast and spindle cell carcinoma of the left breast.
      Although the patient was treated with adjuvant chemotherapy, she had an early
      relapse with pleural, lung and bone metastases. The patient died approximately 8
      months after operation. Spindle cell carcinoma presents many problems about
      therapy and prognosis. Further accumulation analysis is necessary.

PMID- 29650918
TI  - [Hepatocellular Carcinoma with Bile Duct Thrombosis - A Case Report].
AB  - Hepatocellular carcinoma(HCC)is not commonly observed with bile duct
      thrombosis.Here, we report a case of HCC with bile thrombi that extended to the
      liver hilum.The patient was a 61-year-old man who visited us due to untreated
      type B hepatitis.He underwent screening with a CT scan that revealed LDA on the
      right posterior lobe of his liver with infiltration of the bile duct.Generally,
      bile resection and reconstruction should be considered for curative resection for
      bile thrombi; however, we attempted to conserve the common bile duct to preserve
      the options of percutaneous therapy in case of tumor recurrence.We performed
      right lobectomy of the liver.The bile duct thrombus was extracted without bile
      duct resection or reconstruction.The patient is alive 6 months after the surgery
      without any development.

PMID- 29650919
TI  - [A Case of Treated with Laparoscopic Surgery for Intussusception Up to the
      Splenic Flexion Region Due to Cecum Cancer].
AB  - A 93-year-old woman was admitted to the hospital because of
      respiratorydiscomfort. A chest CT scan indicated aspiration pneumonitis and,
      simultaneously, intussusception was observed in the splenic flexure region.
      Abdominal enhance CT scan revealed a tumor in the advanced region of
      intussusception. Laparoscopy-assisted ileocecal resection was performed. Since
      the intussusception was difficult to reduce laparoscopically, the ileocecum was
      mobilized and the intussusception was reduced manually. In the resected specimen,
      a type 1 tumor was observed in the cecum and histopathologic ally diagnosed as
      cercal cancer. We report a case with intussusception due to colorectal cancer
      treated bylaparoscopic surgery.

PMID- 29650920
TI  - [A Case of Chemotherapy with FOLFOXIRI plus Cetuximab for Liver Metastasis of
      Sigmoid ColonCan cer].
AB  - We report a case of chemotherapy with FOLFOXIRI plus cetuximab for liver
      metastasis of sigmoid colon cancer. The patient was a 40's man who was diagnosed
      with sigmoid colon cancer with liver metastasis. Colonoscopy revealed a type 2
      tumor with stenosis in the sigmoid colon. He underwent sigmoidectomy under
      laparotomy, and after the operation, received 7 courses of chemotherapy with
      FOLFOXIRI plus cetuximab. The liver tumor was sufficiently reduced, and
      laparotomy and liver right lobectomy were performed. Histopathology revealed a
      modified, Grade 2 tumor regression. He has been followed for 1 year 4months after
      the operation.

PMID- 29650921
TI  - [A Case of Laparoscopic Whole Layer Cholecystectomy for Elevated Lesion Suspected
      Biliary Cancer].
AB  - A case of attempted laparoscopic cholecystectomy for elevated lesion which was
      clearly early biliary cancer. Laparoscopic cholecystectomy has become popular as
      a minimally invasive surgical method, and is the primary choice for benign
      diseases. However for cases of suspected biliary cancer, open cholecystectomy,
      rather than laparoscopic, is recommended according to medical guidelines. The
      reason for this is that in cases of damage to the gallbladder, bile spillage to
      the abdominal cavity may occur, leading to port site recurrence and peritoneal
      recurrence. In addition, for invasion depth exceeding ss, or in cases of RAS
      cancer, the cancer may become exposed on the resected surface and remain.
      Hypothetically though, if the gallbladder is resected by total layer resection,
      RAS cancer can be removed. At this time, we performed a laparoscopic whole layer
      cholecystectomy for elevated lesion. We would like to report this case along with
      some bibliographic considerations.

PMID- 29650922
TI  - [Gallbladder Carcinoma That Occurred 50 Years after Cholecystojejunostomy].
AB  - Creation of a cholecystojejunostomy has been recommended as one option in the
      palliation of biliary obstruction due to pancreatic carcinoma.However, it was a
      technique used for biliary drainage for acute cholecystitis a long time ago.We
      describe a patient who underwent a cholecystojejunostomy for acute cholecystitis
      50 years prior to presentation, and then revealed a gallbladder carcinoma.

PMID- 29650923
TI  - [A Case of Gastric GIST with Pathological Complete Response Achieved by Long-Term
      Chemotherapy with Imatinib Mesylate].
AB  - A 78-year-old woman was diagnosed with a gastrointestinal stromal tumor(GIST)of
      the stomach, gradually increasing from 5 years prior. The tumor was suspected to
      invade the pancreatic body tail and spleen, as observed with computed tomography.
      Because the patient refused to undergo resection, we administered imatinib
      mesylate for 6 years. Since early rectal cancer was revealed, the patient was
      referred for resection and underwent laparoscopic low anterior resection and
      partial gastrectomy. Histopathologically, the tumor was replaced by tissues with
      myxomatous changes, and no viable tumor cells were detected. This was a rare case
      of GIST, resected after long-term chemotherapy by imatinib mesylate, and
      pathological complete response was achieved.

PMID- 29650924
TI  - [Endoscopy-Assisted Partial Duodenal Resection for Duodenal Adenoma in a Patient
      with Familial Adenomatous Polyposis].
AB  - We here report a case of endoscopy-assisted partial duodenal resection for
      duodenal adenoma in a patient with familial adenomatous polyposis(FAP). A male
      underwent total proctocolectomy with ileal pouch anal anastomosis in 1997. Since
      2004, duodenal adenomas occurred and the atypical grade of adenoma was gradually
      aggravated. Therefore, he underwent endoscopy-assisted partial duodenal resection
      in 2013. The pathological finding of the specimen showed well-differentiated
      tubular adenocarcinoma(pM, ly0, v0). No recurrence has been observed at 4 years
      after the operation. Endoscopy-assisted partial duodenal resection was minimum
      invasive surgery and considered to be useful for the patients with duodenal
      adenoma.

PMID- 29650925
TI  - [A Case of Colon Cancer with Brain, Liver and Lung Metastasis Successfully
      Treated with Bevacizumab plus Xelox Therapy].
AB  - The patient was a 57-year-old woman. Preclinical examination of malignant
      lymphoma revealed 0-I sp type of early rectal cancer in the upper rectum, 20 cm
      from the anal margin. Endoscopic mucosal resection was performed and positive
      deep margins were pathologically diagnosed. Additional intestinal resection with
      lymph node dissection was deemed necessary, but ABVD therapy was initiated
      because the clinical stage of the malignant lymphoma was Stage III b or higher.
      Two months after detecting elevated CEA, S8 liver metastasis was pointed out, and
      examination of weakness of the right upper limb revealed nodular, multifocal
      brain metastasis. After chemotherapy for malignant lymphoma, bevacizumab(BV)plus
      Xelox therapy was initiated. After administering 4 courses, partial loss of
      multiple brain metastases and reduction of the liver metastatic lesion were
      confirmed; therefore, partial resection of the liver via laparoscopy was
      performed. After surgery, BV plus Xelox therapy was resumed, but since the lower
      lobular lung metastasis was confirmed after 8 courses, partial resection of the
      left lower lobe with thoracoscopy was performed. After lung resection, BV plus
      FOLFIRI therapy was administered, and 12 months after the onset of treatment for
      brain metastasis, recurrence was not detected.

PMID- 29650926
TI  - [A Resected Case of Adenosquamous Carcinoma of Pancreas That Relapsed in Remnant
      Pancreas].
AB  - A 70's man underwent subtotal stomach preserving pancreatoduodenectomy(SSPPD)for
      pancreatic head cancer. The pathological diagnosis was adenosquamous
      carcinoma(ASC)of the pancreas. Two months after surgery, a recurrent tumor in the
      remnant pancreas was confirmed with a CT scan and suspected to be ASC by
      endoscopic ultrasound-guided fine needle aspiration(EUS-FNA). As the recurrent
      lesion was limited in the pancreas, total remnant pancreatectomy(TP)was performed
      4 months after SSPPD. The final pathological diagnosis was ASC. Two months after
      TP, liver and para-aortic lymph node metastases were revealed. The patient has
      been alive for 14 months after SSPPD with chemotherapy. Because of its rarity, it
      is difficult to implement treatment plans for recurrent ASC in the remnant
      pancreas.

PMID- 29650927
TI  - [A Case of Long-Term Survival of Metastatic and Recurrent Duodenal
      Gastrointestinal Stromal Tumor Treated with Multimodality Managements].
AB  - We hereby report a case of long-term survival of metastatic and recurrent
      duodenal gastrointestinal stromal tumor(GIST) treated with multimodality
      managements. A 59-year-old man was diagnosed with duodenal GIST and underwent
      surgical resection of a primary lesion of the duodenum. Since the pathological
      findings on mitotic rate indicated its high risk of recurrence, the systemic
      treatment by imatinib mesylate was given shortly after the surgery. Six months
      later, metastatic lesions being considered to be imatinib-resistant were observed
      in the remnant liver. Since there were no other drugs available for GISTs in
      clinic at that time, surgery of central bisegmentectomy with partial resection of
      the liver was performed to eliminate all metastatic lesions. However, recurrences
      had been repeatedly diagnosed afterward. In response to them, four more surgery
      for recurrent liver or peritoneal tumors, two transcatheter arterial
      chemoembolizations(TACE)and one radiofrequency ablation(RFA)were performed on the
      basis of its resectability. Sunitinib malate had been given since it was approved
      for imatinib-resistant GISTs in clinic. Eventually, as long as 99 months had
      passed since we observed the first evidence of the resistance to imatinib
      mesylate when he died from the GIST.

PMID- 29650928
TI  - [Conversion Surgery after Etoposide/Cisplatin(EP)Therapy for Huge Pancreatic
      Neuroendocrine Carcinoma - A Case Report].
AB  - Neuroendocrine carcinoma(NEC)is known as rapid tumor growth, high grade
      malignancy and poor prognosis. We report a case of huge pancreatic NEC
      successfully performed conversion surgery after EP therapy. A 70-year-old female,
      was presented to our hospital with appetite loss. CT scan revealed huge tumor, 15
      cm in diameter, locating at the pancreas with possible involvement to liver,
      stomach, common hepatic artery, left gastric artery and gastroduodenal artery.
      Peritoneal dissemination and para-aortic lymph node metastasis were also
      suspected. EUS-FNA showed neuroendocrine carcinoma with almost 100%positive
      staining rate of Ki-67. We immediately started etoposide/cisplatin(EP)therapy.
      After 6 courses of EP, the tumor shrank remarkably and peritoneal disseminations
      were disappeared. Common hepatic artery and gastroduodenal artery became free
      from the tumor. However, after 7 courses of EP, CT and PET-CT revealed tumor re
      growth. Also renal impairment could not afford to continue EP therapy. Therefore
      we decided to perform conversion surgery. In the guideline in Japan, there is no
      content specialized for surgical treatment for NEC. Moreover, second-line of
      chemotherapy for NEC has not been established. In the future, accumulation of NEC
      cases will contribute to develop effective multidisciplinary treatment.

PMID- 29650929
TI  - [A Case of HER2 Positive Occult Breast Cancer Presenting as Swollen Axillary
      LymphNodes].
AB  - Occult breast cancer, which develops as a metastatic lesion with no primary tumor
      detected in the breast, is a rare breast cancer. A 68-year-old female patient
      particularly complained of the presence of a right axillary mass. The mass in the
      right axilla was palpable, but no tumor was found in both the breasts on
      palpation, ultrasound examination, or MRI. Partial breast resection and axillary
      lymph node dissection were performed following a diagnosis of invasive ductal
      carcinoma by core needle biopsy. There was no mammary gland tissue present around
      the tumor due to the pathology of the disease, and the tumor was diagnosed as
      occult breast cancer. As the cancer was ER negative and HER2 positive, treatment
      with a combination of FEC, docetaxel, and trastuzumab was initiated.
      Radiotherapy, which irradiated the right supraclavicular fossa and the right
      mammary gland, was administered. No disease recurrence and mammary tumor has been
      reported in the patient till date. Treatment of occult breast cancer generally
      includes local therapy such as radiation and surgery. However, in the present
      case, we did not operate upon the breast; instead we treated the right breast and
      the right supraclavicular fossa with radiation therapy. As the tumor was HER2
      positive, we reasoned that local control of disease would be likely if treatment
      with chemotherapy and trastuzumab was performed effectively.

PMID- 29650930
TI  - [A Case of Early Gastric Cancer with Multiple Lymph Node Metastases Revealed by
      Additional Surgical Resection after ESD].
AB  - A 74-year-old man was referred to our hospital for further investigation of a
      cystic lesion in the pancreatic body, which had been detected by ultrasonography
      at a local hospital. He was diagnosed as intraductal papillary mucinous
      neoplasm(IPMN) and further preoperative examinations were conducted. Upper
      gastrointestinal endoscopy demonstrated a type 0-II c tumor of the greater
      curvature in the upper third of the stomach. Endoscopic ultrasonography showed no
      sign of submucosal invasion. Endoscopic submucosal dissection(ESD)was carried out
      and pathological examination of a specimen revealed well differentiated
      adenocarcinoma with submucosal invasion, which fulfilled the indication for
      additional gastrectomy with lymph node dissection. Laparoscopy-assisted proxymal
      gastrectomy with D1 plus lymph node dissection and distal pancreatectomy with
      splenectomy was performed. Pathological examination demonstrated intraductal
      papillary mucious adenoma(IPMA)in the pancreatic body and no residual gastric
      cancer in a specimen, however 7lymph node metastases from gastric cancer was
      confirmed(pN3a), including 3 metastatic lymph nodes incidentally-detected
      adjacent to the pancreatic parenchyma. We report a rare case of early gastric
      cancer with N3 lymph node metastases, with a brief literature review.

PMID- 29650931
TI  - [A Case of Locally Advanced Pancreatic Cancer Successfully Resected after S-1
      Therapy in an Elderly Patient].
AB  - We report a case of locally advanced pancreatic body cancer, accomplishing R0
      resection following preoperative chemotherapy. An 80-year-old female patient was
      admitted to our hospital because of high CA19-9 levels.Based on computed
      tomography images, she was diagnosed with locally advanced cancer of the
      pancreatic body.We started S-1 chemotherapy (100mg/day, 2 weeks administration 1
      week rest)because the tumor was suspected to have invaded the celiac trunk and
      the common hepatic artery.The tumor decreased in size, and the encasement of the
      celiac trunk and the common hepatic artery were released, following 6 months of
      chemotherapy.Subsequently, distal pancreatectomy with D2 lymph node dissection
      was performed.The patient was healthy and showed no signs of recurrence 5 years
      and 9 months after surgery.

PMID- 29650932
TI  - [A Case of Sigmoid Colon Cancer with Locally Advanced Infiltration Curatively
      Resected after CapeOX Therapy].
AB  - A 68-year-old man presented with malaise and abdominal swelling.Lower
      gastrointestinal endoscopy revealed a type 2 circumferential sigmoid colon
      cancer.Computed tomography suggested the cancer infiltrating bladder and
      abdominal wall with abscess.Because of locally advanced infiltration, the patient
      was treated with capecitabine plus oxaliplatin(CapeOX) plus bevacizumab therapy
      after loop-colostomy.After 2 courses of chemotherapy, a CT revealed tumor
      reduction and increased abscess, which was punctured drainage.After 4 courses of
      chemotherapy, a CT revealed abscess reduction, we tried to
      operation.Sigmoidectomy with combined resection of abdominal wall and bladder
      total hysterectomy and fascia lata grafting were performed.The pathological
      diagnosis was tub1, T4b, ly2, v2, PN0, N0, M0, Stage II, pR0, Grade I a.We
      reported a case of curative resection of locally advanced sigmoid colon cancer
      treated with combined resection of bladder and abdominal wall after CapeOX
      therapy.

PMID- 29650933
TI  - [A Case of Laparoscopic Rectal Amputation Performed for Anal Gland Mucinous
      Carcinoma with Pagetoid Spread].
AB  - A 69-year-old man was admitted for the growing anal tumor and referred to our
      hospital. The tumor was about 40mm in size, and by biopsy, he was diagnosed the
      adenocarcinoma. Based on this diagnosis, abdominoperinealresection and edge
      resection were performed. Histopathologicalfindings showed mucinous carcinoma
      originating from analgl and with pagetoid spread. Postoperative chemotherapy was
      not performed, but 1 year 6 months after the surgery, inguinall ymph node
      recurrence was found, and lymph node dissection was performed. One year after the
      operation, recurrence was not found.

PMID- 29650934
TI  - [Giant Retroperitoneal Liposarcoma Treated by Surgical Resection and Chemotherapy
      - A Case Report].
AB  - As the treatment for the liposarcoma, there is no effective chemotherapy and a
      surgical remedy is required. We present the case of a 64-year-old man who
      complained about difficulty in swallowing and discomfort of throat. Computed
      tomography revealed a large enhancing left sided retroperitoneal mass invading
      the retroperitoneal space and it was displaced to the right. Preoperative
      diagnosis was retroperitonealmal ignant tumor. Tumor excision were performed and
      around 4.0 kg tumor was removed though its size was too big and resected it
      separately. Tumors increased 5 months later and became the second enucleation.
      After the second operation, we used eribulin as postoperative adjuvant
      chemotherapy. However, we needed extraction 3 times by the surgery because it
      recurred as peritonealdissemination. We continue surgicaltreatment and
      chemotherapy together as there are a part increasing relatively slowly and a high
      grade part increasing rapidly.

PMID- 29650935
TI  - [Clinicopathological Examination of Differentiated Gastric Cancer].
AB  - OBJECTIVE: The common type carcinoma of gastric cancer is divided into 3 groups,
      papillary adenocarcinoma(pap), well differentiated tubular
      adenocarcinoma(tub1)and moderately tubular adenocarcinoma(tub2). In this study,
      we tried to individualize treatments of them by evaluating their
      clinicopathological features. METHODS: Examined resected specimens were collected
      from 2000 to 2016. We compared among pap, tub1, and tub2 as the
      clincopathological features retrospectively. RESULTS: Histological diagnosis was
      confirmed to 55 cases with pap, 639 cases with tub1 and 718 cases with tub2.
      Comparing the ratio of lymph node metastasis(LNM)according to the depth of
      invasion, tub2 and pap show higher incidence of LNM than tub1 in T1b, T2, and
      T4(a+b). Tub2 and pap patients have larger number of LNM and worse 5 year
      survival rates than tub1 patients. CONCLUSION: We demonstrated that tub2 and pap
      may have higher malignancy and show earlier LNM than tub1. When we consider of
      endoscopic treatment, individualizataing tub1, tub2 and pap is important.

PMID- 29650936
TI  - [Review of the Efficacy of Endoscopic Stenting for Malignant Colorectal
      Obstruction at Tokyo Metropolitan Ohtsuka Hospital].
AB  - BACKGROUND: The use of self-expandable metallic stent(SEMS)was first authorized
      by insurance and became available nationwide in Japan in 2012. Insertion of SEMS
      for colorectal obstruction due to colorectal cancer is useful as a bridge to
      surgery(BTS)approach and releases stenosis as palliative care. AIM: To assess the
      outcomes of SEMS placement for colorectal obstruction. PATIENTS AND METHODS: A
      total of 14 patients were treated with SEMS between April 2014 and March 2017. We
      reviewed their medical records to assess the usefulness of SEMS placement and the
      clinical course. RESULTS: SEMS insertion was effective in 93% of the 14 patients.
      In 10 patients with BTS, the median interval between SEMS insertion and operation
      was 16 days, and no severe complications were noted in them. In 4 patients with
      palliative care, all patients were released from colorectal stenosis. CONCLUSION:
      SEMS placement played a satisfactory role in improvement of patient QOL by paying
      scrupulous attention to a colonic stent retained.

PMID- 29650937
TI  - [An Elderly Case of Recurrent Neuroendocrine Carcinoma of the Stomach Treated
      with Ramucirumab].
AB  - An 84-years-old man underwent total gastrectomy with D1 plus lymph node
      dissection in December 2015, and diagnosed as Stage III B neuroendocrine
      carcinoma of the stomach. An abdominal computed tomography revealed swollen
      paraaortic lymph nodes and left adrenal grand in May 2016. Since his serum level
      of CA19-9 was elevated, he was thus diagnosed as having recurrence, and was
      started chemotherapy with ramucirumab(RAM). After introduction of the
      chemotherapy, his serum level of CA19-9 was decreased gradually and metastatic
      foci were also decreased in size. Although the patient required relatively longer
      administration interval according to the severity of general fatigue, he
      continued the chemotherapy without severe adverse effects until he rejected
      further treatment in January 2017, and satisfactory therapeutic result was
      acquired. While the prognosis of gastric neuroendocrine carcinoma is reported to
      be very poor, no definitive therapeutic guideline is available at present.
      Especially in elderly patients, we should pay considerable attention to the
      selection of chemotherapeutic agents because of their own adverse effects. In the
      present case, RAM could be administered safely, and it seemed that RAM might
      become a useful therapeutic option for gastric neuroendocrine carcinoma even in
      elderly patients.

PMID- 29650938
TI  - [A Distal Bile Duct Carcinoma Patient Who Underwent Surgical Resection for Liver
      Metastasis].
AB  - A 70-year-old man with distal bile duct carcinoma underwent a subtotal stomach
      preserving pancreaticoduodenectomy without adjuvant chemotherapy. One and a half
      years after the surgery, elevated levels of serum SPan-1(38.1 U/mL)were observed
      and CT scans demonstrated a solitary metastasis, 25mm in size, in segment 8 of
      the liver. The patient received 2 courses of gemcitabine-cisplatin combination
      chemotherapy. No new lesions were detected after chemotherapy and the patient
      underwent a partial liver resection of segment 8. The pathological examination
      revealed a metachronous distant metastasis originating from the bile duct
      carcinoma. Subsequently, the patient received S-1 adjuvant chemotherapy for 6
      months. Following completion of all therapies, the patient survived without tumor
      recurrence for 3 years and 10 months after the initial operation. Thus, surgical
      interventions might be effective in improving prognosis among selected patients
      with postoperative liver metastasis of bile duct carcinoma.

PMID- 29650939
TI  - [A Case of Successful Treatment with Gemcitabine plus Nab-Paclitaxel Therapy for
      Nonresected Pancreatic Body Cancer(Stage IVb)].
AB  - A 61-year-old woman was introduced for consultation with a chief complaint of
      frequent vomiting. CT revealed a pancreatic body cancer approximately 40mm in
      size; an invading stenosis from the horizontal part of the duodenum to the
      jejunum, superior mesenteric artery, and portal vein, splenic vein obstruction,
      lymphadenopathy, and some ascitic fluid. We diagnosed a passage disorder due to
      the invasive stenosis from the horizontal part of the duodenum of the pancreatic
      body cancer to the jejunum, and subsequently performed a duodenum and jejunum
      bypass operation. We controlled cancer pain with opioid analgesia, and S-1
      monotherapy was chosen as the primary chemotherapy. A tendency to increase and
      the cancer pain of the tumor was aggravated when 5 courses took effect, so
      gemcitabine plus nab-paclitaxel(GEM plus nab-PTX)therapy was chosen as the second
      line chemotherapy because of adverse Grade 3 events due to difficulties with S-1
      internal use. We tapered off the opioid analgesia dosage because the cancer pain
      was relieved after 1 course. The imaging top indicated stable disease at the end
      of 5 courses, but the pain was relieved so opioid pain killers were unnecessary.
      Foreign continuation is under treatment with 10-course GEM plus nab-PTX therapy
      after initial diagnosis. Currently, the patient has undergone 5 courses of S-1
      for approximately 18 months, and has achieved stable disease. The only adverse
      events were nausea, fatigue, Grade 1 malaise, and Grade 2 alopecia, as detected
      with imaging.

PMID- 29650940
TI  - [A Case of Intraductal Pancreatic Mallignant Tumor with Difficulty in
      Differentiating between IPMN and ITPN].
AB  - The patient was a male in his early 60s. Diabetes had aggravated 6 months
      earlier, and the patient was referred to our hospital for close examination. On
      contrast CT, enhanced mass shadows filling the lumen of the main pancreatic duct,
      which was dilated throughout the pancreas, were observed, and the mass was
      diagnosed as an adenocarcinoma on EUS-FNA. Based on these findings, main-duct
      IPMN was suspected and total pancreatectomy was performed. On macroscopic
      observation of the resected specimen, outgrowth of a solid tumor was observed in
      the main pancreatic duct, whereas only low-level mucus retention was noted in the
      pancreatic duct. Histopathological examination revealed a papillary/tubular tumor
      growth, suggesting interstitial infiltration throughout the pancreas. On
      immunostaining, the tumor was partially positive for MUC5AC, based on which the
      patient was diagnosed with an intraductal pancreatic mallignant tumor, with
      difficulty in differentiating between IPMC and ITPC. Clinicopathologically, many
      aspects regarding ITPN remain unclear. Further accumulation of such cases and
      investigation of the tumor pathology are necessary.

PMID- 29650941
TI  - [A Case of an Intraductal Papillary Mucinous Neoplasm Which Rapidly Worsened and
      Penetrated into the Stomach and the Transverse Colon].
AB  - We report a case of a 71-year-old woman.She visited our hospital with a complaint
      of high fever and abdominal distention. She has been pointed out intraductal
      papillary mucinous neoplasm(IPMN)4 years ago.Abdominal CT showed cystic legion,
      80mm in diameter, on the pancreas.The lesion was unclear at the boundary between
      the main pancreatic duct and in contact with the stomach, transverse colon.Upper
      endoscopic and colonoscopic examination revealed the exhaustion image from the
      intestional tract but not pointed out the malignant findings.We performed total
      pancreatectomy, total gastrectomy and partial transverse colectomy.Pathological
      examination revealed the intraductal papillary mucinous carcinoma but the tumor
      did not invaded the stomach and colon.It is known that some cases of IPMN form
      fistulae to adjacent organs.We report a case of IPMN penetrating into the stomach
      and colon.

PMID- 29650942
TI  - [A Case of Successful Management of Postoperative Chylous Ascites by Combination
      Therapy with Octreotide and Etilefrine].
AB  - We have report a case of an 81-year-old woman who underwent distal pancreatectomy
      for pancreatic body cancer. Chy- lous ascites with high triglyceride(TG)level,
      201mg/dL, occurred on postoperative day 2. Continuous drainage and conservative
      management, such as low fat diet, fasting, total parental nutrition, and
      octreotide monotherapy, could not resolve the problem. Successful treatment was
      achieved using subcutaneous octreotide injection and intravenous etilefrine
      infusion without any adverse side-effect. These medications were able to cause
      smooth muscle contraction in the thoracic duct, and also to reduce chyle flow.
      The amount of drainage decreased and the TG level was restored to 66mg/dL. The
      drainage tube was removed on postoperative day 22, 5 days after the start of both
      octreotide and etilefrine. This combination therapy with octreotide and
      etilefrine would be one of effective and safety treatment for management of
      postoperative intractable chylous ascites.

PMID- 29650943
TI  - [A Useful Case of Photodynamic Diagnosis of Inferior Vena Cava Invasion by
      Pancreatic Head Cancer Using 5-Aminolevulinic Acid(5-ALA)].
AB  - Curative resection is necessary to survival in pancreatic cancer, however after
      surgery, pathologic examination sometimes diagnoses the remains of cancer at the
      resected stump. Therefore, it is necessary to evaluate the stump by
      intraoperative rapid pathological examination. 5-aminolevulinic acid(5-ALA)is an
      endogenous natural amino acid and precursor of the heme pathway. 5-ALA is
      metabolized and accumulated as protoporphyrin IX(Pp IX)that is photosensitive
      substance. 5-ALA mediated photodynamic diagnosis(PDD)(ALA-PDD)has high diagnostic
      ability. Andwe previously reportedusefulness of ALA-PDD for lymph node metastasis
      and peritoneal dissemination in gastric cancer and colorectal cancer patients. A
      case was 73-year-oldman who hadpancreatic headcancer. Since pancreatic cancer
      invasion to the inferior vena cava(IVC)was suspected during the operation,
      fluorescence observation was undergone. Pp IX fluorescence signal observedin the
      tissue around IVC by fluorescence observation. And, the tissue diagnosed
      adenocarcinoma by pathological findings. Therefore, it was judged that curative
      resection was difficult and the operation was completed. In conclusion, it was
      suggested that ALAPDD may be one of the methods of intraoperatively diagnosing
      the residual lesion of pancreatic cancer.

PMID- 29650944
TI  - Glucose-Related Protein 78 Expression and Its Effects on Cisplatin-Resistance in
      Cervical Cancer.
AB  - BACKGROUND GRP78, the 78-kDa glucose-regulated protein, occupies a significant
      position in endoplasmic reticulum stress. Emerging evidences have shown that
      GRP78 induces chemoresistance in several tumors; however, the role of GRP78 in
      cervical cancer (CVC) still needs to be elucidated clearly. MATERIAL AND METHODS
      In the present study, we determined the expression levels of GRP78 in CVC tissues
      collected from patients through immuocytochemistry, western blot and real-time
      PCR. To evaluate the exact role of GRP78 in CVC cells in the presence of
      cisplatin, we generated GRP78 knock-down cervical cancer cells through small
      interfering RNA. After successful transfection, the apoptosis rate was assessed
      with flow cytometry. The expression levels of caspase-3, CHOP and Bcl-2 in GRP78
      knock-down cells were determined by western blot. RESULTS The GRP78 levels in CVC
      tissues were increased significantly. Three types of CVC cells HeLa, SiHa, and
      C33A were treated with different concentrations of cisplatin and cultured for 12
      hours, 24 hours, and 48 hours respectively. And SiHa cells exhibited the highest
      resistance to cisplatin at all time. Specifically, after 25 MUM cisplatin
      treatment, more than 80% of C33A cells underwent apoptosis, whereas the apoptotic
      rate of SiHa cells was only 30-40%. Data suggested that GRP78 silencing increased
      chemo-sensitivity and improved the effects of cisplatin-induced apoptosis in SiHa
      cells. Moreover, inhibition of GRP78 could upregulate caspase-3 and CHOP
      expression and downregulate Bcl-2 expression. CONCLUSIONS GRP78 may represent a
      key bio-marker of CVC and silencing GRP78 may strengthen the resistance against
      cisplatin. GRP78 may be a potential molecular target for CVC therapies in future.

PMID- 29650945
TI  - Impact of Regulatory T Cells on Innate Immune Cells in a Pre-Sensitized Heart
      Transplant Model.
AB  - BACKGROUND Although our previous studies revealed the role of Tregs (regulatory T
      cells) and MDSCs (myeloid-derived suppressor cells) in a pre-sensitized cardiac
      transplant model, interplay between Tregs and NK cells, neutrophils, and
      macrophages remain undefined. MATERIAL AND METHODS Mice heart transplantation
      with skin pre-sensitization was performed, in which prolonged-cold ischemia time
      (PCI) was used for donor treatment. Syngeneic heterotopic heart transplant
      recipients with PCI were treated with PC61 (monoclonal anti-CD25 antibodies),
      adoptive cell transfer with Tregs, and rapamycin. RESULTS We unveiled that both
      rapamycin treatment and adoptive transfer of Tregs could lead to a remarkable
      decrease of frequency of splenic Gr1+ cells (P=0.058 and P=0.016, respectively).
      Although administration of PC61 did not affect frequency of splenic Gr1+ cells,
      it dramatically increased frequency of splenic F4/80+ macrophages (P=0.052).
      Intriguingly, use of both exogenous PC61 and rapamycin induced a dramatic
      augmentation of frequency of Gr-1+ neutrophils in the grafts (PC61: P=0.00029;
      rapamycin: P=0.0096). Noticeably, all different regimens including PC61,
      rapamycin, and adoptive transfer of Tregs, consistently resulted in a remarked
      augmentation of frequency of F4/80+ macrophages within grafts (PC61, P=0.0013;
      rapamycin, P=0.015; Tregs transfer, P=0.013). Although rapamycin and adoptive
      transfer of Tregs did not affect frequency of NK1.1+ cells, administration of
      PC61 dramatically increased frequency of NK1.1+ cells within grafts (P=0.033).
      CONCLUSIONS Tregs depletion or Tregs induced by rapamycin or exogenous cell
      transfer could affect frequencies of both splenic and intragraft neutrophils,
      macrophages, and NK cells, but not splenic NK cells. Our data might shed light on
      understanding sensitized transplant biology.

PMID- 29650946
TI  - A Rare Case of Relapsed Pediatric Acute Promyelocytic Leukemia with Skin
      Involvement by Myeloid Sarcoma.
AB  - BACKGROUND Acute promyelocytic leukemia (APL) is a very rare leukemia in
      children. Extramedullary involvement by APL has been reported in between 3-5% of
      cases, mainly associated with cases of relapse. A rare case of relapse of APL in
      a 9-year-old child is presented with skin involvement with myeloid sarcoma. CASE
      REPORT A 9-year-old male child was admitted to the Oncology Service of the
      hospital complaining of fever, progressive fatigue, oral petechiae with severe
      bleeding in the oral cavity. Bone marrow examination showed some promyelocytes.
      Flow cytometry showed 86% immature myeloid cells with the t(15;17) translocation,
      and molecular analysis showed expression of the PML/RARa fusion protein, which
      confirmed the diagnosis of APL. The patient completed a course of daunorubicin,
      cytarabine, and AII trans-retinoic acid (ATRA) with complete remission. After six
      months, the patient was re-admitted to hospital with a violaceous lesion on the
      scalp, with relapse of APL. Histological and immunohistochemistry of the lesion
      involving the skin of the scalp showed a myeloid sarcoma invading the dermis.
      CONCLUSIONS Myeloid sarcoma, also called granulocytic sarcoma, is an
      extramedullary tumor of immature myeloid cells, which very rarely presents in
      children with APL. The mechanisms that lead to myeloid sarcoma in children with
      APL and the possible association with ATRA therapy remain to be investigated.

PMID- 29650947
TI  - Hsa-let-7c controls the committed differentiation of IGF-1-treated mesenchymal
      stem cells derived from dental pulps by targeting IGF-1R via the MAPK pathways.
AB  - The putative tumor suppressor microRNA let-7c is extensively associated with the
      biological properties of cancer cells. However, the potential involvement of let
      7c in the differentiation of mesenchymal stem cells has not been fully explored.
      In this study, we investigated the influence of hsa-let-7c (let-7c) on the
      proliferation and differentiation of human dental pulp-derived mesenchymal stem
      cells (DPMSCs) treated with insulin-like growth factor 1 (IGF-1) via flow
      cytometry, CCK-8 assays, alizarin red staining, real-time RT-PCR, and western
      blotting. In general, the proliferative capabilities and cell viability of DPMSCs
      were not significantly affected by the overexpression or deletion of let-7c.
      However, overexpression of let-7c significantly inhibited the expression of IGF-1
      receptor (IGF-1R) and downregulated the osteo/odontogenic differentiation of
      DPMSCs, as indicated by decreased levels of several osteo/odontogenic markers
      (osteocalcin, osterix, runt-related transcription factor 2, dentin
      sialophosphoprotein, dentin sialoprotein, alkaline phosphatase, type 1 collagen,
      and dentin matrix protein 1) in IGF-1-treated DPMSCs. Inversely, deletion of let
      7c resulted in increased IGF-1R levels and enhanced osteo/odontogenic
      differentiation. Furthermore, the ERK, JNK, and P38 MAPK pathways were
      significantly inhibited following the overexpression of let-7c in DPMSCs.
      Deletion of let-7c promoted the activation of the JNK and P38 MAPK pathways. Our
      cumulative findings indicate that Let-7c can inhibit the osteo/odontogenic
      differentiation of IGF-1-treated DPMSCs by targeting IGF-1R via the JNK/P38 MAPK
      signaling pathways.

PMID- 29650948
TI  - Pharmaceutical concentration using organic solvent forward osmosis for solvent
      recovery.
AB  - The organic solvent forward osmosis (OSFO) process can simultaneously concentrate
      the active pharmaceutical ingredients (APIs) and recover the organic solvents.
      Here we demonstrate and evaluate an OSFO process for solvent recovery. In this
      demonstration, OSFO was conducted in different solvents with different draw
      solutes. The OSFO process shows rejections >98% when recovering organic solvents
      from different feed solutions, even when the feed concentration is as high as 20
      wt%. More importantly, all systems exhibit relatively low ratios of reverse
      solute flux to solvent flux, indicating that the adverse effects of using
      hazardous draw solutions could be minimized. Nevertheless, the use of non
      hazardous draw solutes such as citric acid is highly recommended to remove any
      potential risk, and it has been demonstrated. Herein, the OSFO process is a
      promising technology for solvent recovery as it possesses a reasonable solvent
      flux, low reverse solute flux and requires no external pressure.

PMID- 29650950
TI  - Interleukin-1 receptor antagonist-mediated neuroprotection by umbilical cord
      derived mesenchymal stromal cells following transplantation into a rodent stroke
      model.
AB  - The human umbilical cord is a promising source of mesenchymal stromal cells
      (MSCs). Intravenous administration of human umbilical cord-derived MSCs (IV
      hUMSCs) showed a favorable effect in a rodent stroke model by a paracrine
      mechanism. However, its underlying therapeutic mechanisms must be determined for
      clinical application. We investigated the therapeutic effects and mechanisms of
      our good manufacturing practice (GMP)-manufactured hUMSCs using various cell
      doses and delivery time points in a rodent model of stroke. IV-hUMSCs at a dose
      of 1 * 106 cells at 24 h after stroke improved functional deficits and reduced
      neuronal damage by attenuation of post-ischemic inflammation. Transcriptome and
      immunohistochemical analyses showed that interleukin-1 receptor antagonist (IL
      1ra) was highly upregulated in ED-1-positive inflammatory cells in rats treated
      with IV-hUMSCs. Treatment with conditioned medium of hUMSCs increased the
      expression of IL-1ra in a macrophage cell line via activation of cAMP-response
      element-binding protein (CREB). These results strongly suggest that the
      attenuation of neuroinflammation mediated by endogenous IL-1ra is an important
      therapeutic mechanism of IV-hUMSCs for the treatment of stroke.

PMID- 29650949
TI  - Treating cat allergy with monoclonal IgG antibodies that bind allergen and
      prevent IgE engagement.
AB  - Acute allergic symptoms are caused by allergen-induced crosslinking of allergen
      specific immunoglobulin E (IgE) bound to Fc-epsilon receptors on effector cells.
      Desensitization with allergen-specific immunotherapy (SIT) has been used for over
      a century, but the dominant protective mechanism remains unclear. One consistent
      observation is increased allergen-specific IgG, thought to competitively block
      allergen binding to IgE. Here we show that the blocking potency of the IgG
      response to Cat-SIT is heterogeneous. Next, using two potent, pre-selected
      allergen-blocking monoclonal IgG antibodies against the immunodominant cat
      allergen Fel d 1, we demonstrate that increasing the IgG/IgE ratio reduces the
      allergic response in mice and in cat-allergic patients: a single dose of blocking
      IgG reduces clinical symptoms in response to nasal provocation (ANCOVA, p =
      0.0003), with a magnitude observed at day 8 similar to that reported with years
      of conventional SIT. This study suggests that simply augmenting the blocking
      IgG/IgE ratio may reverse allergy.

PMID- 29650951
TI  - Immiscible hydrous Fe-Ca-P melt and the origin of iron oxide-apatite ore
      deposits.
AB  - The origin of iron oxide-apatite deposits is controversial. Silicate liquid
      immiscibility and separation of an iron-rich melt has been invoked, but Fe-Ca-P
      rich and Si-poor melts similar in composition to the ore have never been observed
      in natural or synthetic magmatic systems. Here we report experiments on
      intermediate magmas that develop liquid immiscibility at 100 MPa, 1000-1040 
      degrees C, and oxygen fugacity conditions (fO2) of ?FMQ = 0.5-3.3 (FMQ = fayalite
      magnetite-quartz equilibrium). Some of the immiscible melts are highly enriched
      in iron and phosphorous +/- calcium, and strongly depleted in silicon (<5 wt.%
      SiO2). These Si-poor melts are in equilibrium with a rhyolitic conjugate and are
      produced under oxidized conditions (~FMQ + 3.3), high water activity (aH2O >=
      0.7), and in fluorine-bearing systems (1 wt.%). Our results show that increasing
      aH2O and fO2 enlarges the two-liquid field thus allowing the Fe-Ca-P melt to
      separate easily from host silicic magma and produce iron oxide-apatite ores.

PMID- 29650952
TI  - Progress and challenges towards targeted delivery of cancer therapeutics.
AB  - Targeted delivery approaches for cancer therapeutics have shown a steep rise over
      the past few decades. However, compared to the plethora of successful pre
      clinical studies, only 15 passively targeted nanocarriers (NCs) have been
      approved for clinical use and none of the actively targeted NCs have advanced
      past clinical trials. Herein, we review the principles behind targeted delivery
      approaches to determine potential reasons for their limited clinical translation
      and success. We propose criteria and considerations that must be taken into
      account for the development of novel actively targeted NCs. We also highlight the
      possible directions for the development of successful tumor targeting strategies.

PMID- 29650954
TI  - Publisher Correction: Reversible chromism of spiropyran in the cavity of a
      flexible coordination cage.
AB  - The original version of this Article contained an error in Fig. 4c, in which the
      right-most chemical structure included an 'N+' rather than an 'N'. This has been
      corrected in both the PDF and HTML versions of the Article.

PMID- 29650953
TI  - HSP27 is a partner of JAK2-STAT5 and a potential therapeutic target in
      myelofibrosis.
AB  - Heat shock protein 27 (HSP27/HSPB1) is a stress-inducible chaperone that
      facilitates cancer development by its proliferative and anti-apoptotic functions.
      The OGX-427 antisense oligonucleotide against HSP27 has been reported to be
      beneficial against idiopathic pulmonary fibrosis. Here we show that OGX-427 is
      effective in two murine models of thrombopoietin- and JAKV617F-induced
      myelofibrosis. OGX-427 limits disease progression and is associated with a
      reduction in spleen weight, in megakaryocyte expansion and, for the JAKV617F
      model, in fibrosis. HSP27 regulates the proliferation of JAK2V617F-positive cells
      and interacts directly with JAK2/STAT5. We also show that its expression is
      increased in both CD34+ circulating progenitors and in the serum of patients with
      JAK2-dependent myeloproliferative neoplasms with fibrosis. Our data suggest that
      HSP27 plays a key role in the pathophysiology of myelofibrosis and represents a
      new potential therapeutic target for patients with myeloproliferative neoplasms.

PMID- 29650955
TI  - Autonomous robotic searching and assembly of two-dimensional crystals to build
      van der Waals superlattices.
AB  - Van der Waals heterostructures are comprised of stacked atomically thin two
      dimensional crystals and serve as novel materials providing unprecedented
      properties. However, the random natures in positions and shapes of exfoliated two
      dimensional crystals have required the repetitive manual tasks of optical
      microscopy-based searching and mechanical transferring, thereby severely limiting
      the complexity of heterostructures. To solve the problem, here we develop a
      robotic system that searches exfoliated two-dimensional crystals and assembles
      them into superlattices inside the glovebox. The system can autonomously detect
      400 monolayer graphene flakes per hour with a small error rate (<7%) and stack
      four cycles of the designated two-dimensional crystals per hour with few minutes
      of human intervention for each stack cycle. The system enabled fabrication of the
      superlattice consisting of 29 alternating layers of the graphene and the
      hexagonal boron nitride. This capacity provides a scalable approach for
      prototyping a variety of van der Waals superlattices.

PMID- 29650956
TI  - High-sensitivity ion detection at low voltages with current-driven organic
      electrochemical transistors.
AB  - Ions dissolved in aqueous media play a fundamental role in plants, animals, and
      humans. Therefore, the in situ quantification of the ion concentration in aqueous
      media is gathering relevant interest in several fields including biomedical
      diagnostics, environmental monitoring, healthcare products, water and food test
      and control, agriculture industry and security. The fundamental limitation of the
      state-of-art transistor-based approaches is the intrinsic trade-off between
      sensitivity, ion concentration range and operating voltage. Here we show a
      current-driven configuration based on organic electrochemical transistors that
      overcomes this fundamental limit. The measured ion sensitivity exceeds by one
      order of magnitude the Nernst limit at an operating voltage of few hundred
      millivolts. The ion sensitivity normalized to the supply voltage is larger than
      1200 mV V-1 dec-1, which is the largest value ever reported for ion-sensitive
      transistors. The proposed approach is general and can be extended to any
      transistor technology, thus opening opportunities for high-performance
      bioelectronics.

PMID- 29650957
TI  - Two-dimensional materials in functional three-dimensional architectures with
      applications in photodetection and imaging.
AB  - Efficient and highly functional three-dimensional systems that are ubiquitous in
      biology suggest that similar design architectures could be useful in electronic
      and optoelectronic technologies, extending their levels of functionality beyond
      those achievable with traditional, planar two-dimensional platforms. Complex
      three-dimensional structures inspired by origami, kirigami have promise as routes
      for two-dimensional to three-dimensional transformation, but current examples
      lack the necessary combination of functional materials, mechanics designs, system
      level architectures, and integration capabilities for practical devices with
      unique operational features. Here, we show that two-dimensional
      semiconductor/semi-metal materials can play critical roles in this context,
      through demonstrations of complex, mechanically assembled three-dimensional
      systems for light-imaging capabilities that can encompass measurements of the
      direction, intensity and angular divergence properties of incident light.
      Specifically, the mechanics of graphene and MoS2, together with strategically
      configured supporting polymer films, can yield arrays of photodetectors in
      distinct, engineered three-dimensional geometries, including octagonal prisms,
      octagonal prismoids, and hemispherical domes.

PMID- 29650958
TI  - Phosphatase activity tunes two-component system sensor detection threshold.
AB  - Two-component systems (TCSs) are the largest family of multi-step signal
      transduction pathways in biology, and a major source of sensors for
      biotechnology. However, the input concentrations to which biosensors respond are
      often mismatched with application requirements. Here, we utilize a mathematical
      model to show that TCS detection thresholds increase with the phosphatase
      activity of the sensor histidine kinase. We experimentally validate this result
      in engineered Bacillus subtilis nitrate and E. coli aspartate TCS sensors by
      tuning their detection threshold up to two orders of magnitude. We go on to apply
      our TCS tuning method to recently described tetrathionate and thiosulfate sensors
      by mutating a widely conserved residue previously shown to impact phosphatase
      activity. Finally, we apply TCS tuning to engineer B. subtilis to sense and
      report a wide range of fertilizer concentrations in soil. This work will enable
      the engineering of tailor-made biosensors for diverse synthetic biology
      applications.

PMID- 29650959
TI  - In vivo guiding nitrogen-doped carbon nanozyme for tumor catalytic therapy.
AB  - Nanomaterials with intrinsic enzyme-like activities (nanozymes), have been widely
      used as artificial enzymes in biomedicine. However, how to control their in vivo
      performance in a target cell is still challenging. Here we report a strategy to
      coordinate nanozymes to target tumor cells and selectively perform their activity
      to destruct tumors. We develop a nanozyme using nitrogen-doped porous carbon
      nanospheres which possess four enzyme-like activities (oxidase, peroxidase,
      catalase and superoxide dismutase) responsible for reactive oxygen species
      regulation. We then introduce ferritin to guide nitrogen-doped porous carbon
      nanospheres into lysosomes and boost reactive oxygen species generation in a
      tumor-specific manner, resulting in significant tumor regression in human tumor
      xenograft mice models. Together, our study provides evidence that nitrogen-doped
      porous carbon nanospheres are powerful nanozymes capable of regulating
      intracellular reactive oxygen species, and ferritinylation is a promising
      strategy to render nanozymes to target tumor cells for in vivo tumor catalytic
      therapy.

PMID- 29650960
TI  - Two-dimensional electronic transport and surface electron accumulation in MoS2.
AB  - Because the surface-to-volume ratio of quasi-two-dimensional materials is
      extremely high, understanding their surface characteristics is crucial for
      practically controlling their intrinsic properties and fabricating p-type and n
      type layered semiconductors. Van der Waals crystals are expected to have an inert
      surface because of the absence of dangling bonds. However, here we show that the
      surface of high-quality synthesized molybdenum disulfide (MoS2) is a major n
      doping source. The surface electron concentration of MoS2 is nearly four orders
      of magnitude higher than that of its inner bulk. Substantial thickness-dependent
      conductivity in MoS2 nanoflakes was observed. The transfer length method
      suggested the current transport in MoS2 following a two-dimensional behavior
      rather than the conventional three-dimensional mode. Scanning tunneling
      microscopy and angle-resolved photoemission spectroscopy measurements confirmed
      the presence of surface electron accumulation in this layered material. Notably,
      the in situ-cleaved surface exhibited a nearly intrinsic state without electron
      accumulation.

PMID- 29650962
TI  - Vascular endothelial growth factor mediates the therapeutic efficacy of
      mesenchymal stem cell-derived extracellular vesicles against neonatal hyperoxic
      lung injury.
AB  - We previously reported the role of vascular endothelial growth factor (VEGF)
      secreted by mesenchymal stem cells (MSCs) in protecting against neonatal
      hyperoxic lung injuries. Recently, the paracrine protective effect of MSCs was
      reported to be primarily mediated by extracellular vesicle (EV) secretion.
      However, the therapeutic efficacy of MSC-derived EVs and the role of the VEGF
      contained within EVs in neonatal hyperoxic lung injury have not been elucidated.
      The aim of the study was to determine whether MSC-derived EVs attenuate neonatal
      hyperoxic lung injury and, if so, whether this protection is mediated via the
      transfer of VEGF. We compared the therapeutic efficacy of MSCs, MSC-derived EVs
      with or without VEGF knockdown, and fibroblast-derived EVs in vitro with a rat
      lung epithelial cell line challenged with H2O2 and in vivo with newborn Sprague
      Dawley rats exposed to hyperoxia (90%) for 14 days. MSCs (1 * 105 cells) or EVs
      (20 ug) were administered intratracheally on postnatal day 5. The MSCs and MSC
      derived EVs, but not the EVs derived from VEGF-knockdown MSCs or fibroblasts,
      attenuated the in vitro H2O2-induced L2 cell death and the in vivo hyperoxic lung
      injuries, such as impaired alveolarization and angiogenesis, increased cell
      death, and activated macrophages and proinflammatory cytokines. PKH67-stained EVs
      were internalized into vascular pericytes (22.7%), macrophages (21.3%), type 2
      epithelial cells (19.5%), and fibroblasts (4.4%) but not into vascular
      endothelial cells. MSC-derived EVs are as effective as parental MSCs for
      attenuating neonatal hyperoxic lung injuries, and this protection was mediated
      primarily by the transfer of VEGF.

PMID- 29650963
TI  - Epigenetic control of IL-23 expression in keratinocytes is important for chronic
      skin inflammation.
AB  - The chronic skin inflammation psoriasis is crucially dependent on the IL-23/IL-17
      cytokine axis. Although IL-23 is expressed by psoriatic keratinocytes and immune
      cells, only the immune cell-derived IL-23 is believed to be disease relevant.
      Here we use a genetic mouse model to show that keratinocyte-produced IL-23 is
      sufficient to cause a chronic skin inflammation with an IL-17 profile.
      Furthermore, we reveal a cell-autonomous nuclear function for the actin
      polymerizing molecule N-WASP, which controls IL-23 expression in keratinocytes by
      regulating the degradation of the histone methyltransferases G9a and GLP, and
      H3K9 dimethylation of the IL-23 promoter. This mechanism mediates the induction
      of IL-23 by TNF, a known inducer of IL-23 in psoriasis. Finally, in keratinocytes
      of psoriatic lesions a decrease in H3K9 dimethylation correlates with increased
      IL-23 expression, suggesting relevance for disease. Taken together, our data
      describe a molecular pathway where epigenetic regulation of keratinocytes can
      contribute to chronic skin inflammation.

PMID- 29650961
TI  - Identification of rare sequence variation underlying heritable pulmonary arterial
      hypertension.
AB  - Pulmonary arterial hypertension (PAH) is a rare disorder with a poor prognosis.
      Deleterious variation within components of the transforming growth factor-beta
      pathway, particularly the bone morphogenetic protein type 2 receptor (BMPR2),
      underlies most heritable forms of PAH. To identify the missing heritability we
      perform whole-genome sequencing in 1038 PAH index cases and 6385 PAH-negative
      control subjects. Case-control analyses reveal significant overrepresentation of
      rare variants in ATP13A3, AQP1 and SOX17, and provide independent validation of a
      critical role for GDF2 in PAH. We demonstrate familial segregation of mutations
      in SOX17 and AQP1 with PAH. Mutations in GDF2, encoding a BMPR2 ligand, lead to
      reduced secretion from transfected cells. In addition, we identify pathogenic
      mutations in the majority of previously reported PAH genes, and provide evidence
      for further putative genes. Taken together these findings contribute new insights
      into the molecular basis of PAH and indicate unexplored pathways for therapeutic
      intervention.

PMID- 29650964
TI  - TSPAN15 interacts with BTRC to promote oesophageal squamous cell carcinoma
      metastasis via activating NF-kappaB signaling.
AB  - Beta-transducin repeat containing E3 ubiquitin protein ligase (BTRC) is crucial
      for the degradation of IkappaBalpha. Our previous transcriptome sequencing
      analysis revealed that tetraspanin 15 (TSPAN15) was significantly upregulated in
      clinical oesophageal squamous cell carcinoma (OSCC) tissues. Here, we show that
      high TSPAN15 expression in OSCC tissues is significantly associated with lymph
      node and distant metastasis, advanced clinical stage, and poor prognosis.
      Elevated TSPAN15 expression is, in part, caused by the reduction of miR-339-5p.
      Functional studies demonstrate that TSPAN15 promotes metastatic capabilities of
      OSCC cells. We further show that TSPAN15 specifically interacts with BTRC to
      promote the ubiquitination and proteasomal degradation of p-IkappaBalpha, and
      thereby triggers NF-kappaB nuclear translocation and subsequent activation of
      transcription of several metastasis-related genes, including ICAM1, VCAM1, uPA,
      MMP9, TNFalpha, and CCL2. Collectively, our findings indicate that TSPAN15 may
      serve as a new biomarker and/or provide a novel therapeutic target to OSCC
      patients.

PMID- 29650965
TI  - A novel autophagy enhancer as a therapeutic agent against metabolic syndrome and
      diabetes.
AB  - Autophagy is a critical regulator of cellular homeostasis, dysregulation of which
      is associated with diverse diseases. Here we show therapeutic effects of a novel
      autophagy enhancer identified by high-throughput screening of a chemical library
      against metabolic syndrome. An autophagy enhancer increases LC3-I to LC3-II
      conversion without mTOR inhibition. MSL, an autophagy enhancer, activates
      calcineurin, and induces dephosphorylation/nuclear translocation of transcription
      factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy gene
      expression. MSL accelerates intracellular lipid clearance, which is reversed by
      lalistat 2 or Tfeb knockout. Its administration improves the metabolic profile of
      ob/ob mice and ameliorates inflammasome activation. A chemically modified MSL
      with increased microsomal stability improves the glucose profile not only of
      ob/ob mice but also of mice with diet-induced obesity. Our data indicate that our
      novel autophagy enhancer could be a new drug candidate for diabetes or metabolic
      syndrome with lipid overload.

PMID- 29650966
TI  - Understanding the adsorption process in ZIF-8 using high pressure crystallography
      and computational modelling.
AB  - Some porous crystalline solids change their structure upon guest inclusion.
      Unlocking the potential of these solids for a wide variety of applications
      requires full characterisation of the response to adsorption and the underlying
      framework-guest interactions. Here, we introduce an approach to understanding gas
      uptake in porous metal-organic frameworks (MOFs) by loading liquefied gases at
      GPa pressures inside the Zn-based framework ZIF-8. An integrated experimental and
      computational study using high-pressure crystallography, grand canonical Monte
      Carlo (GCMC) and periodic DFT simulations has revealed six symmetry-independent
      adsorption sites within the framework and a transition to a high-pressure phase.
      The cryogenic high-pressure loading method offers a different approach to
      obtaining atomistic detail on guest molecules. The GCMC simulations provide
      information on interaction energies of the adsorption sites allowing to classify
      the sites by energy. DFT calculations reveal the energy barrier of the transition
      to the high-pressure phase. This combination of techniques provides a holistic
      approach to understanding both structural and energetic changes upon adsorption
      in MOFs.

PMID- 29650968
TI  - Electrical and optical properties of epitaxial binary and ternary GeTe-Sb2Te3
      alloys.
AB  - Phase change materials such as pseudobinary GeTe-Sb2Te3 (GST) alloys are an
      essential part of existing and emerging technologies. Here, we investigate the
      electrical and optical properties of epitaxial phase change materials: alpha
      GeTe, Ge2Sb2Te5 (GST225), and Sb2Te3. Temperature-dependent Hall measurements
      reveal a reduction of the hole concentration with increasing temperature in
      Sb2Te3 that is attributed to lattice expansion, resulting in a non-linear
      increase of the resistivity that is also observed in GST225. Fourier transform
      infrared spectroscopy at room temperature demonstrates the presence of electronic
      states within the energy gap for alpha-GeTe and GST225. We conclude that these
      electronic states are due to vacancy clusters inside these two materials. The
      obtained results shed new light on the fundamental properties of phase change
      materials such as the high dielectric constant and persistent photoconductivity
      and have the potential to be included in device simulations.

PMID- 29650967
TI  - Rice auxin influx carrier OsAUX1 facilitates root hair elongation in response to
      low external phosphate.
AB  - Root traits such as root angle and hair length influence resource acquisition
      particularly for immobile nutrients like phosphorus (P). Here, we attempted to
      modify root angle in rice by disrupting the OsAUX1 auxin influx transporter gene
      in an effort to improve rice P acquisition efficiency. We show by X-ray microCT
      imaging that root angle is altered in the osaux1 mutant, causing preferential
      foraging in the top soil where P normally accumulates, yet surprisingly, P
      acquisition efficiency does not improve. Through closer investigation, we reveal
      that OsAUX1 also promotes root hair elongation in response to P limitation.
      Reporter studies reveal that auxin response increases in the root hair zone in
      low P environments. We demonstrate that OsAUX1 functions to mobilize auxin from
      the root apex to the differentiation zone where this signal promotes hair
      elongation when roots encounter low external P. We conclude that auxin and OsAUX1
      play key roles in promoting root foraging for P in rice.

PMID- 29650969
TI  - AKAPs-PKA disruptors increase AQP2 activity independently of vasopressin in a
      model of nephrogenic diabetes insipidus.
AB  - Congenital nephrogenic diabetes insipidus (NDI) is characterized by the inability
      of the kidney to concentrate urine. Congenital NDI is mainly caused by loss-of
      function mutations in the vasopressin type 2 receptor (V2R), leading to impaired
      aquaporin-2 (AQP2) water channel activity. So far, treatment options of
      congenital NDI either by rescuing mutant V2R with chemical chaperones or by
      elevating cyclic adenosine monophosphate (cAMP) levels have failed to yield
      effective therapies. Here we show that inhibition of A-kinase anchoring proteins
      (AKAPs) binding to PKA increases PKA activity and activates AQP2 channels in
      cortical collecting duct cells. In vivo, the low molecular weight compound 3,3'
      diamino-4,4'-dihydroxydiphenylmethane (FMP-API-1) and its derivatives increase
      AQP2 activity to the same extent as vasopressin, and increase urine osmolality in
      the context of V2R inhibition. We therefore suggest that FMP-API-1 may constitute
      a promising lead compound for the treatment of congenital NDI caused by V2R
      mutations.

PMID- 29650970
TI  - Crosstalk between gut microbiota and Sirtuin-3 in colonic inflammation and
      tumorigenesis.
AB  - Colorectal cancer (CRC) is a disease involving a variety of genetic and
      environmental factors. Sirtuin-3 (Sirt3) is expressed at a low level in cancer
      tissues of CRC, but it is unclear how Sirt3 modulates colonic tumorigenesis. In
      this study, we found that gut microbiota play a central role in the resistance to
      CRC tumor formation in wild-type (WT) mice through APC (Adenomatous Polyposis
      Coli)-mutant mouse microbiota transfer via Wnt signaling. We also found that
      Sirt3-deficient mice were hypersusceptible to colonic inflammation and tumor
      development through altered intestinal integrity and p38 signaling, respectively.
      Furthermore, susceptibility to colorectal tumorigenesis was aggravated by initial
      commensal microbiota deletion via Wnt signaling. Mice with Sirt3-deficient
      microbiota transfer followed by chemically induced colon tumorigenesis had low
      Sirt3 expression compared to WT control microbiome transfer, mainly due to a
      decrease in Escherichia/Shigella, as well as an increase in Lactobacillus reuteri
      and Lactobacillus taiwanensis. Collectively, our data revealed that Sirt3 is an
      anti-inflammatory and tumor-suppressing gene that interacts with the gut
      microbiota during colon tumorigenesis.

PMID- 29650971
TI  - Hydrogen sulfide inhibits epithelial-mesenchymal transition in peritoneal
      mesothelial cells.
AB  - Peritoneal fibrosis (PS) determines the long-term outcome of peritoneal dialysis
      (PD). We previous confirmed that hydrogen sulfide (H2S) inhibited PS, but its
      cellular mechanism was not fully elucidated. Epithelial-mesenchymal transition
      (EMT) of mesothelial cells (MCs) is an important cellular event of PS, we
      therefore investigated whether EMT can be affected by H2S in MCs. Rats were
      treated with 4.25% -glucose PD fluids plus lipopolysaccharide for 28 days to
      produce PS, and NaHS (56 MUg/kg.d) was given simultaneously. NaHS (56 MUg/kg.d)
      reduced the deposition of collagen in the submesothelial zone compared with the
      PS group. In primarily cultured rat MCs, 4.25% -glucose PD fluid induced EMT in
      MCs featured as loss of ZO-1 and Cytokeratin, and increase of alpha-SMA,
      plasminogen activator inhibitor 1, fibronectin and TGF-beta1 proteins. PD fluid
      also increased IL-6 and monocyte chemotactic protein-1 mRNA expressions as well
      as the phosphorylation of Smad2/3 and Smad3. NaHS (50-300 MUmol/L) reversed the
      above alterations with the optimal dose at 100 MUmol/L. Thus, exogenous H2S
      improves PS by inhibiting EMT in MCs. The anti-EMT effect of H2S is associated
      with the inhibition of inflammation and TGF-beta1-Smad signal pathway.

PMID- 29650972
TI  - Intentional communication between wild bonnet macaques and humans.
AB  - Comparative studies of nonhuman communication systems could provide insights into
      the origins and evolution of a distinct dimension of human language:
      intentionality. Recent studies have provided evidence for intentional
      communication in different species but generally in captive settings. We report
      here a novel behaviour of food requesting from humans displayed by wild bonnet
      macaques Macaca radiata, an Old World cercopithecine primate, in the Bandipur
      National Park of southern India. Using both natural observations and field
      experiments, we examined four different behavioural components-coo-calls, hand
      extension gesture, orientation, and monitoring behaviour-of food requesting for
      their conformity with the established criteria of intentional communication. Our
      results suggest that food requesting by bonnet macaques is potentially an
      intentionally produced behavioural strategy as all the food requesting behaviours
      except coo-calls qualify the criteria for intentionality. We comment on plausible
      hypotheses for the origin and spread of this novel behavioural strategy in the
      study macaque population and speculate that the cognitive precursors for language
      production may be manifest in the usage of combination of signals of different
      modalities in communication, which could have emerged in simians earlier than in
      the anthropoid apes.

PMID- 29650973
TI  - Author Correction: Striking diflubenzuron resistance in Culex pipiens, the prime
      vector of West Nile Virus.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 29650974
TI  - Publisher Correction: Predictors of chronic kidney disease in type 1 diabetes: a
      longitudinal study from the AMD Annals initiative.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 29650975
TI  - Author Correction: Remodeling of the Actin/Spectrin Membrane-associated Periodic
      Skeleton, Growth Cone Collapse and F-Actin Decrease during Axonal Degeneration.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 29650976
TI  - Wnt signal activation induces midbrain specification through direct binding of
      the beta-catenin/TCF4 complex to the EN1 promoter in human pluripotent stem
      cells.
AB  - The canonical Wnt signal pathway plays a pivotal role in anteroposterior
      patterning and midbrain specification during early neurogenesis. Activating Wnt
      signal has been a strategy for differentiating human pluripotent stem cells
      (PSCs) into midbrain dopaminergic (DA) neurons; however, the underlying molecular
      mechanism(s) of how the Wnt signal drives posterior fate remained unclear. In
      this study, we found that activating the canonical Wnt signal significantly
      upregulated the expression of EN1, a midbrain-specific marker, in a fibroblast
      growth factor signal-dependent manner in human PSC-derived neural precursor cells
      (NPCs). The EN1 promoter region contains a putative TCF4-binding site that
      directly interacts with the beta-catenin/TCF complex upon Wnt signal activation.
      Once differentiated, NPCs treated with a Wnt signal agonist gave rise to
      functional midbrain neurons including glutamatergic, GABAergic, and DA neurons.
      Our results provide a potential molecular mechanism that underlies midbrain
      specification of human PSC-derived NPCs by Wnt activation, as well as a
      differentiation paradigm for generating human midbrain neurons that may serve as
      a cellular platform for studying the ontogenesis of midbrain neurons and
      neurological diseases relevant to the midbrain.

PMID- 29650977
TI  - Deterministic realization of collective measurements via photonic quantum walks.
AB  - Collective measurements on identically prepared quantum systems can extract more
      information than local measurements, thereby enhancing information-processing
      efficiency. Although this nonclassical phenomenon has been known for two decades,
      it has remained a challenging task to demonstrate the advantage of collective
      measurements in experiments. Here, we introduce a general recipe for performing
      deterministic collective measurements on two identically prepared qubits based on
      quantum walks. Using photonic quantum walks, we realize experimentally an
      optimized collective measurement with fidelity 0.9946 without post selection. As
      an application, we achieve the highest tomographic efficiency in qubit state
      tomography to date. Our work offers an effective recipe for beating the precision
      limit of local measurements in quantum state tomography and metrology. In
      addition, our study opens an avenue for harvesting the power of collective
      measurements in quantum information-processing and for exploring the intriguing
      physics behind this power.

PMID- 29650978
TI  - Percutaneous Closure of Left Atrial Appendage significantly affects Lipidome
      Metabolism.
AB  - Patients with non-valvular atrial fibrillation (AF) and a high risk for oral
      anticoagulation can be treated by percutaneous implantation of left atrial
      appendage occlusion devices (LAAC) to reduce the risk of cardio-embolic stroke.
      This study evaluates whether LAAC may influence lipid metabolism, which has never
      been investigated before. Patients with successful LAAC were included
      consecutively. Venous peripheral blood samples of patients were collected
      immediately before (T0, baseline) and 6 months after (T1, mid-term) LAAC. A
      targeted metabolomics approach based on electrospray ionization liquid
      chromatography-mass spectrometry (ESI-LC-MS/MS) and MS/MS measurements was
      performed. A total of 34 lipids revealed a significant change from baseline to
      mid-term follow-up after successful LAAC. Subgroup analysis revealed confounding
      influence by gender, age, diabetes mellitus type II, body mass index, left
      ventricular ejection fraction, creatinine and NT-proBNP. After multivariable
      adjustment within logistic regression models, these 34 lipids were still
      significantly altered after LAAC. Successful percutaneous LAAC may affect lipid
      metabolism and thereby may potentially affect pro-atherogenic and cardio-toxic
      effects.

PMID- 29650979
TI  - Comparative analysis of naive, primed and ground state pluripotency in mouse
      embryonic stem cells originating from the same genetic background.
AB  - Mouse embryonic stem cells (mESCs) exist in a naive, primed and ground state of
      pluripotency. While comparative analyses of these pluripotency states have been
      reported, the mESCs utilized originated from various genetic backgrounds and were
      derived in different laboratories. mESC derivation in conventional LIF + serum
      culture conditions is strain dependent, with different genetic backgrounds
      potentially affecting subsequent stem cell characteristics. In the present study,
      we performed a comprehensive characterization of naive, primed and ground state
      mESCs originating from the same genetic background within our laboratory, by
      comparing their transcriptional profiles. We showed unique transcriptional
      profiles for naive, primed and ground state mESCs. While naive and ground state
      mESCs have more similar but not identical profiles, primed state mESCs show a
      very distinct profile. We further demonstrate that the differentiation propensity
      of mESCs to specific germ layers is highly dependent on their respective state of
      pluripotency.

PMID- 29650980
TI  - Protein docking refinement by convex underestimation in the low-dimensional
      subspace of encounter complexes.
AB  - We propose a novel stochastic global optimization algorithm with applications to
      the refinement stage of protein docking prediction methods. Our approach can
      process conformations sampled from multiple clusters, each roughly corresponding
      to a different binding energy funnel. These clusters are obtained using a density
      based clustering method. In each cluster, we identify a smooth "permissive"
      subspace which avoids high-energy barriers and then underestimate the binding
      energy function using general convex polynomials in this subspace. We use the
      underestimator to bias sampling towards its global minimum. Sampling and subspace
      underestimation are repeated several times and the conformations sampled at the
      last iteration form a refined ensemble. We report computational results on a
      comprehensive benchmark of 224 protein complexes, establishing that our refined
      ensemble significantly improves the quality of the conformations of the original
      set given to the algorithm. We also devise a method to enhance the ensemble from
      which near-native models are selected.

PMID- 29650981
TI  - Optical characterization of surface adlayers and their compositional demixing at
      the nanoscale.
AB  - Under ambient conditions, the behavior of a solid surface is often dominated by a
      molecularly thin adsorbed layer (adlayer) of small molecules. Here we develop an
      optical approach to unveil the nanoscale structure and composition of small
      molecule adlayers on glass surfaces through spectrally resolved super-resolution
      microscopy. By recording the images and emission spectra of millions of
      individual solvatochromic molecules that turn fluorescent in the adlayer phase,
      we obtain ~30 nm spatial resolution and achieve concurrent measurement of local
      polarity. This allows us to establish that the adlayer dimensionality gradually
      increases through a sequence of 0D (nanodroplets), 1D (nano-lines), and 2D
      (films) for liquids of increasing polarity. Moreover, we find that in adlayers, a
      solution of two miscible liquids spontaneously demixes into nanodroplets of
      different compositions that correlate strongly with droplet size and location. We
      thus reveal unexpectedly rich structural and compositional behaviors of surface
      adlayers at the nanoscale.

PMID- 29650982
TI  - A Hyphenated Preconcentrator-Infrared-Hollow-Waveguide Sensor System for N2O
      Sensing.
AB  - Following the Kyoto protocol, all signatory countries must provide an annual
      inventory of greenhouse-gas emission including N2O. This fact associated with the
      wide variety of sources for N2O emissions requires appropriate sensor
      technologies facilitating in-situ monitoring, compact dimensions, ease of
      operation, and sufficient sensitivity for addressing such emission scenarios. In
      this contribution, we therefore describe an innovative portable mid-infrared
      chemical sensor system for quantifying gaseous N2O via coupling a substrate
      integrated hollow waveguide (iHWG) simultaneously serving as highly miniaturized
      mid-infrared photon conduit and gas cell to a custom-made preconcentrator. N2O
      was collected onto a solid sorbent material packed into the preconcentrator unit,
      and then released via thermal desorption into the iHWG-MIR sensor utilizing a
      compact Fourier transform infrared (FTIR) spectrometer for molecularly selective
      spectroscopic detection with a limit of detection (LOD) at 5 ppbv. Highlighting
      the device flexibility in terms of sampling time, flow-rate, and iHWG design
      facilitates tailoring the developed preconcentrator-iHWG device towards a wide
      variety of application scenarios ranging from soil and aquatic emission
      monitoring and drone- or unmanned aerial vehicle (UAV)-mounted monitoring systems
      to clinical/medical analysis scenarios.

PMID- 29650983
TI  - Myotube elasticity of an amyotrophic lateral sclerosis mouse model.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that
      affects the motor system leading to generalized paralysis and death of patients.
      The understanding of early pathogenic mechanisms will help to define early
      diagnostics criteria that will eventually provide basis for efficient
      therapeutics. Early symptoms of ALS usually include muscle weakness or stiffness.
      Therefore, mechanical response of differentiated myotubes from primary cultures
      of mice, expressing the ALS-causing SOD1 G93A mutation, was examined by atomic
      force microscopy. Simultaneous acquisition of topography and cell elasticity of
      ALS myotubes was performed by force mapping method, compared with healthy
      myotubes and supplemented with immunofluorescence and qRT-PCR studies. Wild type
      myotubes reveal a significant difference in elasticity between a narrow and a
      wide population, consistent with maturation occurring with higher actin
      expression relative to myosin together with larger myotube width. However, this
      is not true for SOD1 G93A expressing myotubes, where a significant shift of thin
      population towards higher elastic modulus values was observed. We provide
      evidence that SOD1 mutant induces structural changes that occurs very early in
      muscle development and well before symptomatic stage of the disease. These
      findings could significantly contribute to the understanding of the role of
      skeletal muscle in ALS pathogenesis.

PMID- 29650984
TI  - Hidden complexity in the ontogeny of sexual size dimorphism in male-larger
      beetles.
AB  - Sexual size dimorphism (SSD) is widespread among animals, but its developmental
      mechanisms are not fully undestood. We investigated the proximate causes of SSD
      in three male-larger and one monomorphic scarab beetles using detailed monitoring
      of growth in individual instars. Apart from the finding that SSD in all three
      male-larger species started to develop already in the first larval instar, we
      generally found a high variability in SSD formation among the species as well as
      among instars. Overall, sexual differences in developmental time, average growth
      rate, as well as in the shape of the growth trajectory seem to be the mechanisms
      responsible for SSD ontogeny in scarab beetles. In the third instar, when the
      larvae attain most of their mass, the males had a similar or even lower
      instantaneous growth rate than females and SSD largely developed as a consequence
      of a longer period of rapid growth in males even in cases when the sexes did not
      differ in the total duration of this instar. Our results demonstrate that a
      detailed approach, examining not only the average growth rate and developmental
      time, but also the shape of the growth trajectory, is necessary to elucidate the
      complex development of SSD.

PMID- 29650985
TI  - Publisher Correction: Controlled dynamic screening of excitonic complexes in 2D
      semiconductors.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 29650986
TI  - Author Correction: Diphenyleneiodonium chloride (DPIC) displays broad-spectrum
      bactericidal activity.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 29650987
TI  - Characterization and non-parametric modeling of the developing serum proteome
      during infancy and early childhood.
AB  - Children develop rapidly during the first years of life, and understanding the
      sources and associated levels of variation in the serum proteome is important
      when using serum proteins as markers for childhood diseases. The aim of this
      study was to establish a reference model for the evolution of a healthy serum
      proteome during early childhood. Label-free quantitative proteomics analyses were
      performed for 103 longitudinal serum samples collected from 15 children at birth
      and between the ages of 3-36 months. A flexible Gaussian process-based
      probabilistic modelling framework was developed to evaluate the effects of
      different variables, including age, living environment and individual variation,
      on the longitudinal expression profiles of 266 reliably identified and quantified
      serum proteins. Age was the most dominant factor influencing approximately half
      of the studied proteins, and the most prominent age-associated changes were
      observed already during the first year of life. High inter-individual variability
      was also observed for multiple proteins. These data provide important details on
      the maturing serum proteome during early life, and evaluate how patterns detected
      in cord blood are conserved in the first years of life. Additionally, our novel
      modelling approach provides a statistical framework to detect associations
      between covariates and non-linear time series data.

PMID- 29650988
TI  - The C-terminal HRET sequence of Kv1.3 regulates gating rather than targeting of
      Kv1.3 to the plasma membrane.
AB  - Kv1.3 channels are expressed in several cell types including immune cells, such
      as T lymphocytes. The targeting of Kv1.3 to the plasma membrane is essential for
      T cell clonal expansion and assumed to be guided by the C-terminus of the
      channel. Using two point mutants of Kv1.3 with remarkably different features
      compared to the wild-type Kv1.3 (A413V and H399K having fast inactivation
      kinetics and tetraethylammonium-insensitivity, respectively) we showed that both
      Kv1.3 channel variants target to the membrane when the C-terminus was truncated
      right after the conserved HRET sequence and produce currents identical to those
      with a full-length C-terminus. The truncation before the HRET sequence (NOHRET
      channels) resulted in reduced membrane-targeting but non-functional phenotypes.
      NOHRET channels did not display gating currents, and coexpression with wild-type
      Kv1.3 did not rescue the NOHRET-A413V phenotype, no heteromeric current was
      observed. Interestingly, mutants of wild-type Kv1.3 lacking HRET(E) (deletion) or
      substituted with five alanines for the HRET(E) motif expressed current
      indistinguishable from the wild-type. These results demonstrate that the C
      terminal region of Kv1.3 immediately proximal to the S6 helix is required for the
      activation gating and conduction, whereas the presence of the distal region of
      the C-terminus is not exclusively required for trafficking of Kv1.3 to the plasma
      membrane.

PMID- 29650989
TI  - Quantization of geometric phase with integer and fractional topological
      characterization in a quantum Ising chain with long-range interaction.
AB  - An attempt is made to study and understand the behavior of quantization of
      geometric phase of a quantum Ising chain with long range interaction. We show the
      existence of integer and fractional topological characterization for this model
      Hamiltonian with different quantization condition and also the different
      quantized value of geometric phase. The quantum critical lines behave differently
      from the perspective of topological characterization. The results of duality and
      its relation to the topological quantization is presented here. The symmetry
      study for this model Hamiltonian is also presented. Our results indicate that the
      Zak phase is not the proper physical parameter to describe the topological
      characterization of system with long range interaction. We also present quite a
      few exact solutions with physical explanation. Finally we present the relation
      between duality, symmetry and topological characterization. Our work provides a
      new perspective on topological quantization.

PMID- 29650990
TI  - Disclosing the temperature of columnar jointing in lavas.
AB  - Columnar joints form by cracking during cooling-induced contraction of lava,
      allowing hydrothermal fluid circulation. A lack of direct observations of their
      formation has led to ambiguity about the temperature window of jointing and its
      impact on fluid flow. Here we develop a novel thermo-mechanical experiment to
      disclose the temperature of columnar jointing in lavas. Using basalts from
      Eyjafjallajokull volcano (Iceland) we show that contraction during cooling
      induces stress build-up below the solidus temperature (980  degrees C), resulting
      in localised macroscopic failure between 890 and 840  degrees C. This temperature
      window for incipient columnar jointing is supported by modelling informed by
      mechanical testing and thermal expansivity measurements. We demonstrate that
      columnar jointing takes place well within the solid state of volcanic rocks, and
      is followed by a nonlinear increase in system permeability of <9 orders of
      magnitude during cooling. Columnar jointing may promote advective cooling in
      magmatic-hydrothermal environments and fluid loss during geothermal drilling and
      thermal stimulation.

PMID- 29650991
TI  - A new way of producing pediocin in Pediococcus acidilactici through intracellular
      stimulation by internalized inulin nanoparticles.
AB  - One of the most challenging aspects of probiotics as a replacement for
      antibiotics is to enhance their antimicrobial activity against pathogens. Given
      that prebiotics stimulate the growth and/or activity of probiotics, we developed
      phthalyl inulin nanoparticles (PINs) as prebiotics and observed their effects on
      the cellular and antimicrobial activities of Pediococcus acidilactici (PA).
      First, we assessed the internalization of PINs into PA. The internalization of
      PINs was largely regulated by glucose transporters in PA, and the process was
      energy-dependent. Once internalized, PINs induced PA to produce substantial
      amounts of antimicrobial peptide (pediocin), which is effective against both Gram
      positive (Salmonella Gallinarum) and Gram-negative (Listeria monocytogenes)
      pathogens. When treated with small-sized PINs, PA witnessed a nine-fold increase
      in antimicrobial activity. The rise in pediocin activity in PA treated with PINs
      was accompanied by enhanced expression of stress response genes (groEL, groES,
      dnaK) and pediocin biosynthesis genes (pedA, pedD). Although the mechanism is not
      clear, it appears that the internalization of PINs by PA causes mild stress to
      activate the PA defense system, leading to increased production of pediocin.
      Overall, we identified a prebiotic in nanoparticle form for intracellular
      stimulation of probiotics, demonstrating a new avenue for the biological
      production of antimicrobial peptides.

PMID- 29650993
TI  - Author Correction: Slow Wave Applications of Electromagnetically Induced
      Transparency in Microstrip Resonator.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 29650992
TI  - Stabilised frequency of extreme positive Indian Ocean Dipole under 1.5  degrees C
      warming.
AB  - Extreme positive Indian Ocean Dipole (pIOD) affects weather, agriculture,
      ecosystems, and public health worldwide, particularly when exacerbated by an
      extreme El Nino. The Paris Agreement aims to limit warming below 2  degrees C and
      ideally below 1.5  degrees C in global mean temperature (GMT), but how extreme
      pIOD will respond to this target is unclear. Here we show that the frequency
      increases linearly as the warming proceeds, and doubles at 1.5  degrees C warming
      from the pre-industrial level (statistically significant above the 90% confidence
      level), underscored by a strong intermodel agreement with 11 out of 13 models
      producing an increase. However, in sharp contrast to a continuous increase in
      extreme El Nino frequency long after GMT stabilisation, the extreme pIOD
      frequency peaks as the GMT stabilises. The contrasting response corresponds to a
      50% reduction in frequency of an extreme El Nino preceded by an extreme pIOD from
      that projected under a business-as-usual scenario.

PMID- 29650995
TI  - Author Correction: Understanding the effect of wet etching on damage resistance
      of surface scratches.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 29650994
TI  - Tuning Ising superconductivity with layer and spin-orbit coupling in two
      dimensional transition-metal dichalcogenides.
AB  - Systems simultaneously exhibiting superconductivity and spin-orbit coupling are
      predicted to provide a route toward topological superconductivity and
      unconventional electron pairing, driving significant contemporary interest in
      these materials. Monolayer transition-metal dichalcogenide (TMD) superconductors
      in particular lack inversion symmetry, yielding an antisymmetric form of spin
      orbit coupling that admits both spin-singlet and spin-triplet components of the
      superconducting wavefunction. Here, we present an experimental and theoretical
      study of two intrinsic TMD superconductors with large spin-orbit coupling in the
      atomic layer limit, metallic 2H-TaS2 and 2H-NbSe2. We investigate the
      superconducting properties as the material is reduced to monolayer thickness and
      show that high-field measurements point to the largest upper critical field thus
      reported for an intrinsic TMD superconductor. In few-layer samples, we find the
      enhancement of the upper critical field is sustained by the dominance of spin
      orbit coupling over weak interlayer coupling, providing additional candidate
      systems for supporting unconventional superconducting states in two dimensions.

PMID- 29650997
TI  - Author Correction: Microplastics in Spanish Table Salt.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 29650996
TI  - Embryonic Exposure to Valproic Acid Impairs Social Predispositions of Newly
      Hatched Chicks.
AB  - Biological predispositions to attend to visual cues, such as those associated
      with face-like stimuli or with biological motion, guide social behavior from the
      first moments of life and have been documented in human neonates, infant monkeys
      and domestic chicks. Impairments of social predispositions have been recently
      reported in neonates at high familial risk of Autism Spectrum Disorder (ASD).
      Using embryonic exposure to valproic acid (VPA), an anticonvulsant associated to
      increased risk of developing ASD, we modeled ASD behavioral deficits in domestic
      chicks. We then assessed their spontaneous social predispositions by comparing
      approach responses to a stimulus containing a face configuration, a stuffed hen,
      vs. a scrambled version of it. We found that this social predisposition was
      abolished in VPA-treated chicks, whereas experience-dependent mechanisms
      associated with filial imprinting were not affected. Our results suggest a
      specific effect of VPA on the development of biologically-predisposed social
      orienting mechanisms, opening new perspectives to investigate the neurobiological
      mechanisms involved in early ASD symptoms.

PMID- 29650998
TI  - A mega-analysis of expression quantitative trait loci (eQTL) provides insight
      into the regulatory architecture of gene expression variation in liver.
AB  - Genome-wide association studies (GWAS) have identified numerous genetic variants
      in the human genome associated with diseases and traits. Nevertheless, for most
      loci the causative variant is still unknown. Expression quantitative trait loci
      (eQTL) in disease relevant tissues is an excellent approach to correlate genetic
      association with gene expression. While liver is the primary site of gene
      transcription for two pathways relevant to age-related macular degeneration
      (AMD), namely the complement system and cholesterol metabolism, we explored the
      contribution of AMD associated variants to modulate liver gene expression. We
      extracted publicly available data and computed the largest eQTL data set for
      liver tissue to date. Genotypes and expression data from all studies underwent
      rigorous quality control. Subsequently, Matrix eQTL was used to identify
      significant local eQTL. In total, liver samples from 588 individuals revealed
      202,489 significant eQTL variants affecting 1,959 genes (Q-Value < 0.001). In
      addition, a further 101 independent eQTL signals were identified in 93 of the
      1,959 eQTL genes. Importantly, our results independently reinforce the notion
      that high density lipoprotein metabolism plays a role in AMD pathogenesis. Taken
      together, our study generated a first comprehensive map reflecting the genetic
      regulatory landscape of gene expression in liver.

PMID- 29650999
TI  - Beyond dose: Pulsed antibiotic treatment schedules can maintain individual
      benefit while reducing resistance.
AB  - The emergence of treatment-resistant microbes is a key challenge for disease
      treatment and a leading threat to human health and wellbeing. New drugs are
      always in development, but microbes regularly and rapidly acquire resistance. We
      must consider if altering how we administer drugs at the individual level could
      slow development of resistance. Here we use mathematical models to show that
      exposing microbes to drug pulses could greatly reduce resistance without
      increasing individual pathogen load. Our results stem from two key factors: the
      presence of antibiotics creates a selection pressure for antibiotic resistant
      microbes, and large populations of bacteria are more likely to harbor drug
      resistance than small populations. Drug pulsing targets these factors
      simultaneously. Short duration pulses minimize the time during which there is
      selection for resistance, and high drug concentrations minimize pathogen
      abundance. Our work provides a theoretical basis for the design of in vitro and
      in vivo experiments to test how drug pulsing might reduce the impact of drug
      resistant infections.

PMID- 29651000
TI  - Author Correction: Localization and function of neurosecretory protein GM, a
      novel small secretory protein, in the chicken hypothalamus.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 29651001
TI  - Effects of green tea on miRNA and microbiome of oral epithelium.
AB  - Consumption of green tea (GT) extracts or purified catechins has shown the
      ability to prevent oral and other cancers and inhibit cancer progression in
      rodent models, but the evidence for this in humans is mixed. Working with humans,
      we sought to understand the source of variable responses to GT by examining its
      effects on oral epithelium. Lingual epithelial RNA and lingual and gingival
      microbiota were measured before and after 4 weeks of exposure in tobacco smokers,
      whom are at high risk of oral cancer. GT consumption had on average inconsistent
      effects on miRNA expression in the oral epithelium. Only analysis that examined
      paired miRNAs, showing changed and coordinated expression with GT exposure,
      provided evidence for a GT effect on miRNAs, identifying miRNAs co-expressed with
      two hubs, miR-181a-5p and 301a-3p. An examination of the microbiome on cancer
      prone lingual mucosa, in contrast, showed clear shifts in the relative abundance
      of Streptococcus and Staphylococcus, and other genera after GT exposure. These
      data support the idea that tea consumption can consistently change oral bacteria
      in humans, which may affect carcinogenesis, but argue that GT effects on oral
      epithelial miRNA expression in humans vary between individuals.

PMID- 29651002
TI  - Metformin Decreases the Incidence of Pancreatic Ductal Adenocarcinoma Promoted by
      Diet-induced Obesity in the Conditional KrasG12D Mouse Model.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is a particularly deadly disease. Chronic
      conditions, including obesity and type-2 diabetes are risk factors, thus making
      PDAC amenable to preventive strategies. We aimed to characterize the chemo
      preventive effects of metformin, a widely used anti-diabetic drug, on PDAC
      development using the KrasG12D mouse model subjected to a diet high in fats and
      calories (HFCD). LSL-KrasG12D/+;p48-Cre (KC) mice were given control diet (CD),
      HFCD, or HFCD with 5 mg/ml metformin in drinking water for 3 or 9 months. After 3
      months, metformin prevented HFCD-induced weight gain, hepatic steatosis,
      depletion of intact acini, formation of advanced PanIN lesions, and stimulation
      of ERK and mTORC1 in pancreas. In addition to reversing hepatic and pancreatic
      histopathology, metformin normalized HFCD-induced hyperinsulinemia and
      hyperleptinemia among the 9-month cohort. Importantly, the HFCD-increased PDAC
      incidence was completely abrogated by metformin (p < 0.01). The obesogenic diet
      also induced a marked increase in the expression of TAZ in pancreas, an effect
      abrogated by metformin. In conclusion, administration of metformin improved the
      metabolic profile and eliminated the promoting effects of diet-induced obesity on
      PDAC formation in KC mice. Given the established safety profile of metformin, our
      findings have a strong translational potential for novel chemo-preventive
      strategies for PDAC.

PMID- 29651004
TI  - Author Correction: Disturbance Regimes Drive The Diversity of Regional Floristic
      Pools Across Guianan Rainforest Landscapes.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 29651003
TI  - piRNA-like small RNAs are responsible for the maternal-specific knockdown in the
      ascidian Ciona intestinalis Type A.
AB  - The mRNAs stored in eggs are crucial for embryogenesis. To address functions of
      maternal mRNAs, we recently reported the novel method MASK (maternal mRNA
      specific knockdown), which we used to specifically knockdown maternal transcripts
      in the ascidian Ciona intestinalis Type A. In MASK, the cis element of a maternal
      gene is fused with eGFP or Kaede reporter gene, and the cassette is introduced
      into Ciona genome by transposon-mediated transgenesis. In eggs of the transgenic
      lines, the maternal expression of the gene whose cis element is used for driving
      the reporter gene is suppressed. The zygotic expression of the gene is not
      suppressed, suggesting that the MASK method can distinguish between maternal and
      zygotic functions of a gene. Here we investigated the cis and trans factors
      responsible for MASK results. In the ovaries in which knockdown of a maternal
      gene occurs, a number of antisense small RNAs are expressed that are
      complementary to the sequence of the knocked-down genes. We suspect that these
      antisense small RNAs are the factor responsible for MASK results. The antisense
      small RNAs have several features that are seen in PIWI-interacting RNAs (piRNAs),
      suggesting that MASK is likely to use a piRNA-mediated mechanism to knock down
      maternal mRNAs.

PMID- 29651005
TI  - Differential effect of morphine on gastrointestinal transit, colonic contractions
      and nerve-evoked relaxations in Toll-Like Receptor deficient mice.
AB  - Toll-like receptors (TLRs) are expressed in enteric neurons, glia,
      gastrointestinal (GI) smooth muscle and mucosa, yet their functional roles in the
      GI tract are not fully understood. TLRs have been linked to many of the
      undesirable central effects of chronic opioid administration including
      hyperalgesia and dependence via activation of central microglia. Opioid-induced
      bowel dysfunction (OIBD) remains a primary reason for the reduction or withdrawal
      of opioid analgesics. Morphine-induced inhibition of colonic motility was
      assessed in vivo by GI transit studies and in vitro using isolated colons from
      wildtype (WT) and TLR deficient mice. Morphine slowed movement of ingested
      content in WT but this retardation effect was attenuated in TLR4 -/- and TLR2/4 
      /- . In isolated colons, morphine reduced amplitude and frequency colonic
      migrating motor contractions in both WT and TLR2/4 -/- . Electrical field
      stimulation elicited distal colon relaxation that was potentiated by morphine in
      WT but not in TLR2/4 -/- . Inhibitory junction potentials were of similar
      amplitude and kinetics in WT and TLR2/4 -/- distal colon and not altered by
      morphine. Enteric nerve density and proportion of nitrergic nerves were similar
      in WT and TLR2/4 -/- distal colon. These data suggest an involvement of TLRs in
      opioid pharmacodynamics and thus a potential interventional target for OIBD.

PMID- 29651006
TI  - Cyclin-dependent kinase 5 mediates pleiotrophin-induced endothelial cell
      migration.
AB  - Pleiotrophin (PTN) stimulates endothelial cell migration through binding to
      receptor protein tyrosine phosphatase beta/zeta (RPTPbeta/zeta) and alphanubeta3
      integrin. Screening for proteins that interact with RPTPbeta/zeta and potentially
      regulate PTN signaling, through mass spectrometry analysis, identified cyclin
      dependent kinase 5 (CDK5) activator p35 among the proteins displaying high
      sequence coverage. Interaction of p35 with the serine/threonine kinase CDK5 leads
      to CDK5 activation, known to be implicated in cell migration. Protein
      immunoprecipitation and proximity ligation assays verified p35-RPTPbeta/zeta
      interaction and revealed the molecular association of CDK5 and RPTPbeta/zeta. In
      endothelial cells, PTN activates CDK5 in an RPTPbeta/zeta- and phosphoinositide 3
      kinase (PI3K)-dependent manner. On the other hand, c-Src, alphanubeta3 and ERK1/2
      do not mediate the PTN-induced CDK5 activation. Pharmacological and genetic
      inhibition of CDK5 abolished PTN-induced endothelial cell migration, suggesting
      that CDK5 mediates PTN stimulatory effect. A new pyrrolo[2,3-alpha]carbazole
      derivative previously identified as a CDK1 inhibitor, was found to suppress CDK5
      activity and eliminate PTN stimulatory effect on cell migration, warranting its
      further evaluation as a new CDK5 inhibitor. Collectively, our data reveal that
      CDK5 is activated by PTN, in an RPTPbeta/zeta-dependent manner, regulates PTN
      induced cell migration and is an attractive target for the inhibition of PTN pro
      angiogenic properties.

PMID- 29651007
TI  - Small-conductance Ca2+-activated K+ channels: insights into their roles in
      cardiovascular disease.
AB  - Life-threatening malignant arrhythmias in pathophysiological conditions can
      increase the mortality and morbidity of patients with cardiovascular diseases.
      Cardiac electrical activity depends on the coordinated propagation of excitatory
      stimuli and the generation of action potentials in cardiomyocytes. Action
      potential formation results from the opening and closing of ion channels. Recent
      studies have indicated that small-conductance calcium-activated potassium (SK)
      channels play a critical role in cardiac repolarization in pathophysiological but
      not normal physiological conditions. The aim of this review is to describe the
      role of SK channels in healthy and diseased hearts, to suggest cardiovascular
      pathophysiologic targets for intervention, and to discuss studies of agents that
      target SK channels for the treatment of cardiovascular diseases.

PMID- 29651008
TI  - Hybrid cluster precursors of the LaZrO insulator for transistors: lowering the
      processing temperature.
AB  - Solution processing of ternary and multinary amorphous metal oxide insulators at
      processing temperatures below 250  degrees C remains challenging. Here, we report
      that the synthesis of a hybrid cluster structure, where the metal oxide core is
      coordinated by ligands and the different metal elements are incorporated into one
      core, is an effective strategy for the low-temperature processing of the ternary
      LaZrO insulator. Solvothermal treatment at 160-180  degrees C facilitated the
      development of a cluster structure. From the cluster precursor, high-performance
      insulating LaZrO films were obtained at 200  degrees C under the irradiation of
      ultraviolet light. The analysis data indicate that the solvothermal treatment led
      to structural unification of the metal oxide network and facilitated
      stabilization of the residual organic ingredients in UV annealing, which both
      contributed to the improved insulating properties of LaZrO. Together with a
      solution-processed channel, we have been able to fabricate LaZrO-based
      transistors at 200  degrees C. Though the channel material has not been
      optimized, the transistor have showed a low gate leakage current around 10 pA at
      an operating voltage of 15 V, an on/off ratio of near 106, a field-effect
      saturation mobility of 0.37 cm2 V-1 s-1, a subthreshold swing factor of 0.61 V
      decade-1.

PMID- 29651009
TI  - Diversity and bioactive potential of culturable fungal endophytes of Dysosma
      versipellis; a rare medicinal plant endemic to China.
AB  - The plant Dysosma versipellis is known for its antimicrobial and anticancer
      properties but is a rare and vulnerable perennial herb that is endemic to China.
      In this study, 224 isolates were isolated from various tissues of D. versipellis,
      and were classified into 53 different morphotypes according to culture
      characteristics and were identified by sequence analyses of the internal
      transcribed spacer (ITS) region of the rRNA gene. Although nine strains were not
      assignable at the phylum level, 44 belonged to at least 29 genera of 15 orders of
      Ascomycota (93%), Basidiomycota (6%), and Zygomycota (1%). Subsequent assays
      revealed antimicrobial activities of 19% of endophytic extracts against at least
      one pathogenic bacterium or fungus. Antimicrobial activity was also determined
      using the agar diffusion method and was most prominent in extracts from four
      isolates. Moreover, high performance liquid chromatography (HPLC) and ultra
      performance liquid chromatography-quadrupole-time of flight mass spectrometry
      analyses (UPLC-QTOF MS) showed the presence of podophyllotoxin in two Fusarium
      strains, with the highest yield of 277 MUg/g in Fusarium sp. (WB5121). Taken
      together, the present data suggest that various endophytic fungi of D.
      versipellis could be exploited as sources of novel natural antimicrobial or
      anticancer agents.

PMID- 29651010
TI  - Dietary supplementation with flaxseed meal and oat hulls modulates intestinal
      histomorphometric characteristics, digesta- and mucosa-associated microbiota in
      pigs.
AB  - The establishment of a healthy gastrointestinal milieu may not only offer an
      opportunity to reduce swine production costs but could also open the way for a
      lifetime of human health improvement. This study investigates the effects of
      feeding soluble fibre from flaxseed meal-containing diet (FM) and insoluble fibre
      from oat hulls-containing diet (OH) on histomorphological characteristics,
      digesta- and mucosa-associated microbiota and their associations with metabolites
      in pig intestines. In comparison with the control (CON) and OH diets, the
      consumption of FM increased (P < 0.001) the jejunal villi height (VH) and the
      ratio of VH to crypt depths. The PERMANOVA analyses showed distinct (P < 0.05)
      microbial communities in ileal digesta and mucosa, and caecal mucosa in CON and
      FM-diets fed pigs compared to the OH diet-fed pigs. The predicted functional
      metagenomes indicated that amino acids and butanoate metabolism, lysine
      degradation, bile acids biosynthesis, and apoptosis were selectively enhanced at
      more than 2.2 log-folds in intestinal microbiota of pigs fed the FM diet. Taken
      together, flaxseed meal and oat hulls supplementation in growing pigs' diets
      altered the gastrointestinal development, as well as the composition and function
      of microbial communities, depending on the intestinal segment and physicochemical
      property of the dietary fibre source.

PMID- 29651011
TI  - Super-resolution for asymmetric resolution of FIB-SEM 3D imaging using AI with
      deep learning.
AB  - Scanning electron microscopy equipped with a focused ion beam (FIB-SEM) is a
      promising three-dimensional (3D) imaging technique for nano- and meso-scale
      morphologies. In FIB-SEM, the specimen surface is stripped by an ion beam and
      imaged by an SEM installed orthogonally to the FIB. The lateral resolution is
      governed by the SEM, while the depth resolution, i.e., the FIB milling direction,
      is determined by the thickness of the stripped thin layer. In most cases, the
      lateral resolution is superior to the depth resolution; hence, asymmetric
      resolution is generated in the 3D image. Here, we propose a new approach based on
      an image-processing or deep-learning-based method for super-resolution of 3D
      images with such asymmetric resolution, so as to restore the depth resolution to
      achieve symmetric resolution. The deep-learning-based method learns from high
      resolution sub-images obtained via SEM and recovers low-resolution sub-images
      parallel to the FIB milling direction. The 3D morphologies of polymeric nano
      composites are used as test images, which are subjected to the deep-learning
      based method as well as conventional methods. We find that the former yields
      superior restoration, particularly as the asymmetric resolution is increased. Our
      super-resolution approach for images having asymmetric resolution enables
      observation time reduction.

PMID- 29651012
TI  - MEMS based highly sensitive dual FET gas sensor using graphene decorated Pd-Ag
      alloy nanoparticles for H2 detection.
AB  - A low power, dual-gate field-effect transistor (FET) hydrogen gas sensor with
      graphene decorated Pd-Ag for hydrogen sensing applications was developed. The FET
      hydrogen sensor was integrated with a graphene-Pd-Ag-gate FET (GPA-FET) as
      hydrogen sensor coupled with Pt-gate FET as a reference sensor on a single sensor
      platform. The sensing gate electrode was modified with graphene by an e-spray
      technique followed by Pd-Ag DC/MF sputtering. Morphological and structural
      properties were studied by FESEM and Raman spectroscopy. FEM simulations were
      performed to confirm the uniform temperature control at the sensing gate
      electrode. The GPA-FET showed a high sensing response to hydrogen gas at the
      temperature of 25~254.5  degrees C. The as-proposed FET H2 sensor showed the fast
      response time and recovery time of 16 s, 14 s, respectively at the operating
      temperature of 245  degrees C. The variation in drain current was positively
      related with increased working temperature and hydrogen concentration. The
      proposed dual-gate FET gas sensor in this study has potential applications in
      various fields, such as electronic noses and automobiles, owing to its low-power
      consumption, easy integration, good thermal stability and enhanced hydrogen
      sensing properties.

PMID- 29651013
TI  - Information about peer choices shapes human risky decision-making.
AB  - Humans frequently make choices that involve risk for health and well-being. At
      the same time, information about others' choices is omnipresent due to new forms
      of social media and information technology. However, while past research has
      shown that peers can exert a strong influence on such risky choices,
      understanding how information about risky decisions of others affects one's own
      risky decisions is still lacking. We therefore developed a behavioral task to
      measure how information about peer choices affects risky decision-making and call
      it the social Balloon Analogue Risk Task (sBART). We tested this novel paradigm
      in a sample of 52 college young adults. Here we show that risky decisions were
      influenced in the direction of the perceived choices of others - riskier choices
      of others led to riskier behavior whereas safer choices of others led to less
      risky behavior. These findings indicate that information about peer choices is
      sufficient to shape one's own risky behavior.

PMID- 29651015
TI  - Author Correction: REM sleep respiratory behaviours match mental content in
      narcoleptic lucid dreamers.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 29651014
TI  - Altered connection properties of important network hubs may be neural risk
      factors for individuals with primary insomnia.
AB  - Primary insomnia (PIs) is highly prevalent and can lead to adverse socioeconomic
      impacts, but the underlying mechanism of its complex brain network impairment
      remains largely unknown. Functional studies are too few and diverse in
      methodology, which makes it difficult to glean general conclusions. To answer
      this question, we first used graph theory-based network analyse, together with
      seed-based functional connectivity approach, to characterize the topology
      architecture of whole-brain functional networks associated with PIs. Forty-eight
      subjects with PIs and 48 age/sex/education-matched good sleepers were recruited.
      We found PIs is associated with altered connection properties of intra-networks
      within the executive control network, default mode network and salience network,
      and inter-network between auditory language comprehension center and executive
      control network. These complex networks were correlated with negative emotions
      and insomnia severity in the PIs group. Altered connection properties of these
      network hubs appeared to be neural risk factors for neuropsychological changes of
      PIs, and might be used as potential neuroimaging markers to distinguish the PIs
      from the good sleepers. These findings highlight the role of functional
      connectivity in the pathophysiology of PIs, and may underlie the neural
      mechanisms of etiology of PIs.

PMID- 29651016
TI  - Design principles for enhancing phase sensitivity and suppressing phase
      fluctuations simultaneously in biochemical oscillatory systems.
AB  - Biological systems need to function accurately in the presence of strong noise
      and at the same time respond sensitively to subtle external cues. Here we study
      design principles in biochemical oscillatory circuits to achieve these two
      seemingly incompatible goals. We show that energy dissipation can enhance phase
      sensitivity linearly by driving the phase-amplitude coupling and increase timing
      accuracy by suppressing phase diffusion. Two general design principles in the key
      underlying reaction loop formed by two antiparallel pathways are found to
      optimize oscillation performance with a given energy budget: balancing the
      forward-to-backward flux ratio between the two pathways to reduce phase diffusion
      and maximizing the net flux of the phase-advancing pathway relative to that of
      the phase-retreating pathway to enhance phase sensitivity. Experimental evidences
      consistent with these design principles are found in the circadian clock of
      cyanobacteria. Future experiments to test the predicted dependence of phase
      sensitivity on energy dissipation are proposed.

PMID- 29651017
TI  - Effects of different doses of granulocyte colony-stimulating factor mobilization
      therapy on ischemic cardiomyopathy.
AB  - G-CSF mobilization might be beneficial to ICM, but the relationship between
      effect/safety and the dosage of G-CSF remains unclear. In this study, 24 pigs
      were used to build ICM models and were randomized into four groups. Four weeks
      later, different dosages of G-CSF were given daily by subcutaneous injection for
      5 days. Another 4 weeks later, all the animals were sacrificed.
      Electrocardiography, coronary arteriography, left ventriculography, transthoracic
      echocardiography, cardiac MRI, and SPECT, histopathologic analysis, and
      immunohistochemistry techniques were used to evaluate left ventricular function
      and myocardial infarct size. Four weeks after G-CSF treatment, pigs in middle
      dose G-CSF group exhibited obvious improvements of left ventricular remodeling
      and function. Moderate G-CSF mobilization ameliorated the regional contractility
      of ICM, preserved myocardial viability, and reduced myocardial infarct size. More
      neovascularization and fewer apoptotic myocardial cells were observed in the
      ischemic region of the heart in middle-dose group. Expression of vWF, VEGF and
      MCP-1 were up-regulated, and Akt1 was activated in high- and middle-dose groups.
      Moreover, CRP, TNF-alpha and S-100 were elevated after high-dose G-CSF
      mobilization. Middle-dose G-CSF mobilization therapy is an effective and safe
      treatment for ICM, and probably acts via a mechanism involving promoting
      neovascularization, inhibiting cardiac fibrosis and anti-apoptosis.

PMID- 29651018
TI  - Affective and cognitive rather than somatic symptoms of depression predict 3-year
      mortality in patients on chronic hemodialysis.
AB  - Depression is more common in many medical conditions than among the general
      population and is associated with an increased risk of mortality. We aimed to
      determine whether somatic symptoms of depression were more predictive of
      mortality than affective and cognitive symptoms in hemodialysis patients. We
      conducted a prospective cohort study in which the survival outcomes of 151
      subjects were followed for more than 3 years. Depression was assessed with the
      Taiwanese Depression Questionnaire (TDQ). Subjects with TDQ scores 19-54
      (correlated with clinically significant depressive symptoms) and those with
      scores 15-18 had higher 3-year mortality rates than the two groups with lower
      scores (40.0%, 46.7%, 16.0% and 19.6%, p = 0.021, ANOVA). Affective and cognitive
      symptoms, including sadness, tenseness, indecisiveness and low self-confidence,
      and one somatic item (bodily discomfort) were associated with mortality.
      Affective and cognitive symptoms affected quality of life more than somatic
      symptoms. The somatic subscale was associated with female gender, low income and
      education, dialysis vintage, and low serum creatinine and albumin levels, whereas
      the affective and cognitive subscale was associated with less education and a low
      serum albumin level. In conclusion, affective and cognitive symptoms of
      depression may better predict long-term mortality in patients undergoing chronic
      hemodialysis than somatic symptoms.

PMID- 29651019
TI  - Author Correction: Comparative genomic and transcriptomic analyses of Family-1
      UDP glycosyltransferase in three Brassica species and Arabidopsis indicates
      stress-responsive regulation.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 29651021
TI  - Sustained caloric restriction in health.

PMID- 29651022
TI  - Disposable all-printed electronic biosensor for instantaneous detection and
      classification of pathogens.
AB  - A novel disposable all-printed electronic biosensor is proposed for a fast
      detection and classification of bacteria. This biosensor is applied to classify
      three types of popular pathogens: Salmonella typhimurium, and the Escherichia
      coli strains JM109 and DH5-alpha. The proposed sensor consists of inter-digital
      silver electrodes fabricated through an inkjet material printer and silver
      nanowires uniformly decorated on the electrodes through the electrohydrodynamic
      technique on a polyamide based polyethylene terephthalate substrate. The best
      sensitivity of the proposed sensor is achieved at 200 um teeth spaces of the
      inter-digital electrodes along the density of the silver nanowires at 30 *
      103/mm2. The biosensor operates on +/-2.5 V and gives the impedance value against
      each bacteria type in 8 min after sample injection. The sample data are measured
      through an impedance analyzer and analyzed through pattern recognition methods
      such as linear discriminate analysis, maximum likelihood, and back propagation
      artificial neural network to classify each type of bacteria. A perfect
      classification and cross-validation is achieved by using the unique fingerprints
      extracted from the proposed biosensor through all the applied classifiers. The
      overall experimental results demonstrate that the proposed disposable all-printed
      biosensor is applicable for the rapid detection and classification of pathogens.

PMID- 29651020
TI  - GFI1 facilitates efficient DNA repair by regulating PRMT1 dependent methylation
      of MRE11 and 53BP1.
AB  - GFI1 is a transcriptional regulator expressed in lymphoid cells, and an
      "oncorequisite" factor required for development and maintenance of T-lymphoid
      leukemia. GFI1 deletion causes hypersensitivity to ionizing radiation, for which
      the molecular mechanism remains unknown. Here, we demonstrate that GFI1 is
      required in T cells for the regulation of key DNA damage signaling and repair
      proteins. Specifically, GFI1 interacts with the arginine methyltransferase PRMT1
      and its substrates MRE11 and 53BP1. We demonstrate that GFI1 enables PRMT1 to
      bind and methylate MRE11 and 53BP1, which is necessary for their function in the
      DNA damage response. Thus, our results provide evidence that GFI1 can adopt non
      transcriptional roles, mediating the post-translational modification of proteins
      involved in DNA repair. These findings have direct implications for treatment
      responses in tumors overexpressing GFI1 and suggest that GFI1's activity may be a
      therapeutic target in these malignancies.

PMID- 29651023
TI  - Generation of autochthonous mouse models of clear cell renal cell carcinoma:
      mouse models of renal cell carcinoma.
AB  - Renal cell carcinoma (RCC) is one of the 10 most common cancers worldwide, and to
      date, a strong systemic therapy has not been developed to treat RCC, even with
      the remarkable modern advances in molecular medicine mostly due to our incomplete
      understanding of its tumorigenesis. There is a dire unmet need to understand the
      etiology and progression of RCC, especially the most common subtype, clear cell
      RCC (ccRCC), and to develop new treatments for RCC. Genetically engineered mouse
      (GEM) models are able to mimic the initiation, progression, and metastasis of
      cancer, thus providing valuable insights into tumorigenesis and serving as
      perfect preclinical platforms for drug testing and biomarker discovery. Despite
      substantial advances in the molecular investigation of ccRCC and monumental
      efforts that have been performed to try to establish autochthonous animal models
      of ccRCC, this goal has not been achieved until recently. Here we present a
      review of the most exciting progress relevant to GEM models of ccRCC.

PMID- 29651025
TI  - Cardiac eccentric remodeling in patients with rheumatoid arthritis.
AB  - It is known that patients with rheumatoid arthritis (RA) have a higher risk of
      coronary heart disease and sudden cardiac death. Abnormalities in cardiac
      geometry appear to be involved in the setting of the cardiovascular risk, but it
      has never been specifically investigated in RA. We enrolled 44 patients with RA
      compared to 131 subjects without RA (normal, N): The RA aged between 18 and 70
      years (mean 48.3 +/- 2.1), 25 females, BMI 27.6 +/- 0.9; N, of equal age (48.6 +/
      1.2, n.s.), included 80 females (BMI 26.7 +/- 0.2, ns). Cardiac Ultrasounds
      showed an increase of the diameter of the left ventricle but not in the septum
      with reduction of relative wall thickness (RWT) in the RA population compared to
      N. Relative wall thickness inversely correlates with biochemical parameters of
      inflammatory response (gamma globulin, p < 0.03; F = 5,660) and anti
      citrullinated peptides antibody (anti-CCP Ab) (p < 0.02; F = 7,1620) We conclude
      that unfavorable cardiac remodeling can increase cardiovascular risk in patients
      with RA.

PMID- 29651026
TI  - Development of a mouse model for the visual and quantitative assessment of
      lymphatic trafficking and function by in vivo imaging.
AB  - Methods for quantitative analysis of long distance lymphatic transport of
      nanoparticles in live animals are yet to be established. We established a mouse
      model for analysis of time-dependent transport just beneath the abdominal skin to
      investigate lymph node-to-lymph node trafficking by in vivo imaging. For this
      purpose, popliteal lymph nodes (PLNs) as well as efferent and afferent lymphatic
      vessels, marginal veins, and feeding blood vessels were surgically resected to
      change the lymphatic flow from footpad injections. Using this model, we observed
      a novel lymphatic flow from the footpad to the proper axillary lymph node (ALN)
      via the inguinal lymph node (ILN). This drainage pathway was maintained over 12
      weeks. Time-dependent transportation of 1,1'-dioctadecyltetramethyl
      indotricarbocyanine iodide-labelled liposomes from the footpad to the ILN was
      successfully quantified by an in vivo imaging system. Moreover, congestion and
      development of a new collateral lymphatic route was visualised under a lymphedema
      status. Histological analysis of abdominal skin tissues of this model revealed
      that PLN resection had no effect on the abdominal lymphatic system between the
      ILN and ALN. These data indicate that this model might be useful to clarify the
      mechanisms of lymphedema and study direct transportation of lymph or other
      substances between lymph nodes.

PMID- 29651024
TI  - Small de novo CNVs as biomarkers of parental exposure to low doses of ionizing
      radiation of caesium-137.
AB  - The radiological accident in Goiania in 1987 caused a trail of human
      contamination, animal, plant and environmental by a radionuclide. Exposure to
      ionizing radiation results in different types of DNA lesions. The mutagenic
      effects of ionizing radiation on the germline are special concern because they
      can endures for several generations, leading to an increase in the rate of
      mutations in children of irradiated parents. Thus, to evaluate the biological
      mechanisms of ionizing radiation in somatic and germline cells, with consequent
      determination of the rate mutations, is extremely important for the estimation of
      genetic risks. Recently it was established that Chromosomal Microarray Analysis
      is an important tool for detecting wide spectra of gains or losses in the human
      genome. Here we present the results of the effect of accidental exposure to low
      doses of ionizing radiation on the formation of CNVs in the progeny of a human
      population accidentally exposed to Caesium-137 during the radiological accident
      in Goiania, Brazil.

PMID- 29651027
TI  - Author Correction: The effect of foreign language in fear acquisition.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 29651028
TI  - Author Correction: Mapping the epidemic changes and risks of hemorrhagic fever
      with renal syndrome in Shaanxi Province, China, 2005-2016.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 29651029
TI  - Calculating curly arrows from ab initio wavefunctions.
AB  - Despite being at the heart of chemical thought, the curly arrow notation of
      reaction mechanisms has been treated with suspicion-the connection with rigorous
      molecular quantum mechanics being unclear. The connection requires a view of the
      wavefunction that goes beyond molecular orbitals and rests on the most
      fundamental property of electrons. The antisymmetry of electronic wavefunctions
      requires that an N-electron wavefunction repeat itself in 3N dimensions, thus
      exhibiting tiles. Inspection of wavefunction tiles permits insight into structure
      and mechanism. Here, we demonstrate that analysis of the wavefunction tile along
      a reaction coordinate reveals the electron movements depicted by the curly arrow
      notation for several reactions. The Diels-Alder reaction is revealed to involve
      the separation and counter propagation of electron spins. This unprecedented
      method of extracting the movements of electrons during a chemical reaction is a
      breakthrough in connecting traditional depictions of chemical mechanism with
      state-of-the-art quantum chemical calculations.

PMID- 29651030
TI  - Publisher Correction: Impaired oxidative stress response characterizes HUWE1
      promoted X-linked intellectual disability.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 29651031
TI  - Author Correction: Vertex coloring of graphs via phase dynamics of coupled
      oscillatory networks.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 29651032
TI  - Author Correction: Development and validation of risk prediction models for
      cardiovascular mortality in Chinese people initialising peritoneal dialysis: a
      cohort study.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 29651033
TI  - Break the Interacting Bridge between Eu3+ Ions in the 3D Network Structure of
      CdMoO4: Eu3+ Bright Red Emission Phosphor.
AB  - Eu3+ doped CdMoO4 super red emission phosphors with charge compensation were
      prepared by the traditional high temperature solid-state reaction method in air
      atmosphere. The interrelationships between photoluminescence properties and
      crystalline environments were investigated in detail. The 3D network structure
      which composed by CdO8 and MoO4 polyhedra can collect and efficiently transmit
      energy to Eu3+ luminescent centers. The relative distance between Eu3+ ions
      decreased and energy interaction increased sharply with the appearance of
      interstitial occupation of O2- ions ([Formula: see text]). Therefore,
      fluorescence quenching occurs at the low concentration of Eu3+ ions in the 3D
      network structure. Fortunately, the charge compensator will reduce the
      concentration of [Formula: see text] which can break the energetic interaction
      between Eu3+ ions. The mechanism of different charge compensators has been
      studied in detail. The strong excitation band situated at ultraviolet and near
      ultraviolet region makes it a potential red phosphor candidate for n-UV based
      LED.

PMID- 29651034
TI  - A new failure mechanism of electromigration by surface diffusion of Sn on Ni and
      Cu metallization in microbumps.
AB  - Microbumps in three-dimensional integrated circuit now becomes essential
      technology to reach higher packaging density. However, the small volume of
      microbumps dramatically changes the characteristics from the flip-chip (FC)
      solder joints. For a 20 um diameter microbump, the cross-section area and the
      volume are only 1/25 and 1/125 of a 100 um diameter FC joint. The small area
      significantly enlarges the current density although the current crowding effect
      was reduced at the same time. The small volume of solder can be fully transformed
      into the intermetallic compounds (IMCs) very easily, and the IMCs are usually
      stronger under electromigration (EM). These result in the thoroughly change of
      the EM failure mechanism in microbumps. In this study, microbumps with two
      different diameter and flip-chip joints were EM tested. A new failure mechanism
      was found obviously in microbumps, which is the surface diffusion of Sn. Under EM
      testing, Sn atoms tend to migrate along the surface to the circumference of Ni
      and Cu metallization to form Ni3Sn4 and Cu3Sn IMCs respectively. When the Sn
      diffuses away, necking or serious void formation occurs in the solder, which
      weakens the electrical and mechanical properties of the microbumps. Theoretic
      calculation indicates that this failure mode will become even significantly for
      the microbumps with smaller dimensions than the 18 um microbumps.

PMID- 29651035
TI  - Impact of sequencing depth on the characterization of the microbiome and
      resistome.
AB  - Developments in high-throughput next generation sequencing (NGS) technology have
      rapidly advanced the understanding of overall microbial ecology as well as
      occurrence and diversity of specific genes within diverse environments. In the
      present study, we compared the ability of varying sequencing depths to generate
      meaningful information about the taxonomic structure and prevalence of
      antimicrobial resistance genes (ARGs) in the bovine fecal microbial community.
      Metagenomic sequencing was conducted on eight composite fecal samples originating
      from four beef cattle feedlots. Metagenomic DNA was sequenced to various depths,
      D1, D0.5 and D0.25, with average sample read counts of 117, 59 and 26 million,
      respectively. A comparative analysis of the relative abundance of reads aligning
      to different phyla and antimicrobial classes indicated that the relative
      proportions of read assignments remained fairly constant regardless of depth.
      However, the number of reads being assigned to ARGs as well as to microbial taxa
      increased significantly with increasing depth. We found a depth of D0.5 was
      suitable to describe the microbiome and resistome of cattle fecal samples. This
      study helps define a balance between cost and required sequencing depth to
      acquire meaningful results.

PMID- 29651036
TI  - Charge mobility retrieval approach from apparent charge packet movements based on
      the negative differential resistance theory.
AB  - Space charge migration characteristics play an important role in the evaluation
      of polymer insulation performance. However, an accurate description of charge
      carrier mobility in several typical insulating polymers such as polyethylene,
      polypropylene is currently not available. Recently, with the observation of a
      series of negative charge packet movements associated with the negative
      differential resistance characteristic of charge mobility in LDPE films, the
      extraction of charge mobility from the apparent charge packet movement has been
      attempted using appropriate methods. Based on the previous report of the
      successful derivation of charge mobility from experimental results using
      numerical methods, the present research improves the derivation accuracy and
      describes the details of the charge mobility derivation procedure. Back
      simulation results under several typical polarizing fields using the derived
      charge mobility are exhibited. The results indicate that both the NDR theory and
      the simulation models for the polyethylene materials are reasonable. A
      significant migration velocity difference between the charge carrier and the
      charge packet is observed. Back simulations of the charge packet under several
      typical polarizing fields using the obtained E-v curve show good agreement with
      the experimental results. The charge packet shapes during the migrations were
      also found to vary with the polarizing field.

PMID- 29651038
TI  - Author Correction: Shape evolution of ooids: a geometric model.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 29651037
TI  - Electron density modulation of NiCo2S4 nanowires by nitrogen incorporation for
      highly efficient hydrogen evolution catalysis.
AB  - Metal sulfides for hydrogen evolution catalysis typically suffer from unfavorable
      hydrogen desorption properties due to the strong interaction between the adsorbed
      H and the intensely electronegative sulfur. Here, we demonstrate a general
      strategy to improve the hydrogen evolution catalysis of metal sulfides by
      modulating the surface electron densities. The N modulated NiCo2S4 nanowire
      arrays exhibit an overpotential of 41 mV at 10 mA cm-2 and a Tafel slope of 37 mV
      dec-1, which are very close to the performance of the benchmark Pt/C in alkaline
      condition. X-ray photoelectron spectroscopy, synchrotron-based X-ray absorption
      spectroscopy, and density functional theory studies consistently confirm the
      surface electron densities of NiCo2S4 have been effectively manipulated by N
      doping. The capability to modulate the electron densities of the catalytic sites
      could provide valuable insights for the rational design of highly efficient
      catalysts for hydrogen evolution and beyond.

PMID- 29651039
TI  - Comprehensive Modeling of Multimode Fiber Sensors for Refractive Index
      Measurement and Experimental Validation.
AB  - We propose and develop a comprehensive model for estimating the refractive index
      (RI) response over three potential sensing zones in a multimode fiber. The model
      has been developed based on a combined ray optics, Gaussian beam, and wave optics
      analysis coupled to the consideration of the injected interrogating lightwave
      characteristics and validated experimentally through the realization of three
      sensors with different lengths of stripped cladding sections as the sensing
      region. The experimental results highly corroborate and validate the simulation
      output from the model for the three RI sensing zones. The sensors can be employed
      over a very wide dynamic RI range from 1.316 to over 1.608 at a wavelength of
      1550 nm, with the best resolution of 2.2447 * 10-5 RI unit (RIU) obtained in Zone
      II for a 1-cm sensor length.

PMID- 29651040
TI  - Isolation and characterization of a multifunctional flavonoid glycosyltransferase
      from Ornithogalum caudatum with glycosidase activity.
AB  - Glycosyltransferases (GTs) are bidirectional biocatalysts catalyzing the
      glycosylation of diverse molecules. However, the extensive applications of GTs in
      glycosides formation are limited due to their requirements of expensive
      nucleotide diphosphate (NDP)-sugars or NDP as the substrates. Here, in an effort
      to characterize flexible GTs for glycodiversification of natural products, we
      isolated a cDNA, designated as OcUGT1 from Ornithogalum caudatum, which encoded a
      flavonoid GT that was able to catalyze the trans-glycosylation reactions,
      allowing the formation of glycosides without the additions of NDP-sugars or NDP.
      In addition, OcUGT1 was observed to exhibit additional five types of functions,
      including classical sugar transfer reaction and three reversible reactions namely
      NDP-sugar synthesis, sugars exchange and aglycons exchange reactions, as well as
      enzymatic hydrolysis reaction, suggesting OcUGT1 displays both
      glycosyltransferase and glycosidase activities. Expression profiles revealed that
      the expression of OcUGT1 was development-dependent and affected by environmental
      factors. The unusual multifunctionality of OcUGT1 broadens the applicability of
      OcUGT1, thereby generating diverse carbohydrate-containing structures.

PMID- 29651041
TI  - Duplication and diversification of lectin receptor-like kinases (LecRLK) genes in
      soybean.
AB  - Lectin receptor-like kinases (LecRLKs) play important roles in plant development
      and stress responses. Although genome-wide studies of LecRLKs have been performed
      in several species, a comprehensive analysis including evolutionary, structural
      and functional analysis has not been carried out in soybean (Glycine max). In
      this study, we identified 185 putative LecRLK genes in the soybean genome,
      including 123 G-type, 60 L-type and 2 C-type LecRLK genes. Tandem duplication and
      segmental duplication appear to be the main mechanisms of gene expansion in the
      soybean LecRLK (GmLecRLK) gene family. According to our phylogenetic analysis, G
      type and L-type GmLecRLK genes can be organized into fourteen and eight
      subfamilies, respectively. The subfamilies within the G-type GmLecRLKs differ
      from each other in gene structure and/or protein domains and motifs, which
      indicates that the subfamilies have diverged. The evolution of L-type GmLecRLKs
      has been more conservative: most genes retain the same gene structures and nearly
      the same protein domain and motif architectures. Furthermore, the expression
      profiles of G-type and L-type GmLecRLK genes show evidence of functional
      redundancy and divergence within each group. Our results contribute to a better
      understanding of the evolution and function of soybean LecRLKs and provide a
      framework for further functional investigation of them.

PMID- 29651042
TI  - Effects of scavenger receptors-1 class A stimulation on macrophage morphology and
      highly modified advanced glycation end product-protein phagocytosis.
AB  - Advanced glycation end-products (AGEs), which comprise non-enzymatically
      glycosylated proteins, lipids, and nucleic acid amino groups, play an important
      role in several diseases and aging processes including angiopathy, renal failure,
      diabetic complications, and neurodegenerative diseases. Among AGE-associated
      phenotypes, toxic AGEs, glyceraldehyde-derived AGE-2, and glycolaldehyde-derived
      AGE-3 are involved in the pathogenesis of diabetic complications. In addition,
      macrophages are reported to remove extracellular AGEs from tissues via scavenger
      receptors, leading to the progression of atherosclerosis. In the present study,
      we found that AGE-2 and AGE-3 enhanced their own endocytic uptake by RAW264.7
      mouse macrophage-like cells in a concentration-dependent manner. Furthermore, we
      demonstrated, for the first time, the morphology of phagocytic macrophages and
      the endocytosis of AGE particles. The toxic AGEs induced the expression of a
      scavenger receptor, CD204/scavenger receptors-1 class A (SR-A). Notably, an
      antibody against CD204 significantly prevented toxic AGE uptake. Moreover, an SR
      A antagonistic ligand, fucoidan, also attenuated the AGE-2- and AGE-3-evoked
      uptake in a concentration-dependent manner. These results indicated that SR-A
      stimulation, at least in part, plays a role in AGE uptake.

PMID- 29651044
TI  - Yeast aconitase mitochondrial import is modulated by interactions of its C and N
      terminal domains and Ssa1/2 (Hsp70).
AB  - Molecules of single proteins, echoforms, can be distributed between two (or more)
      subcellular locations, a phenomenon which we refer to as dual targeting or dual
      localization. The yeast aconitase gene ACO1 (778 amino acids), encodes a single
      translation product that is nonetheless dual localized to the cytosol and
      mitochondria by a reverse translocation mechanism. The solved crystal structure
      of aconitase isolated from porcine heart mitochondria shows that it has four
      domains. The first three tightly associated N-terminal domains are tethered to
      the larger C-terminal fourth domain (C-terminal amino acids 517-778). We have
      previously shown that the aconitase C terminal domain constitutes an independent
      dual targeting signal when fused to mitochondria-targeted passenger-proteins. We
      show that the aconitase N and C-terminal domains interact and that this
      interaction is important for efficient aconitase post translational import into
      mitochondria and for aconitase dual targeting (relative levels of aconitase
      echoforms). Our results suggest a "chaperone-like function" of the C terminal
      domain towards the N terminal domains which can be modulated by Ssa1/2 (cytosolic
      Hsp70).

PMID- 29651043
TI  - A cell surface display fluorescent biosensor for measuring MMP14 activity in real
      time.
AB  - Despite numerous recent advances in imaging technologies, one continuing
      challenge for cell biologists and microscopists is the visualization and
      measurement of endogenous proteins as they function within living cells.
      Achieving this goal will provide a tool that investigators can use to associate
      cellular outcomes with the behavior and activity of many well-studied target
      proteins. Here, we describe the development of a plasmid-based fluorescent
      biosensor engineered to measure the location and activity of matrix
      metalloprotease-14 (MMP14). The biosensor design uses fluorogen-activating
      protein technology coupled with a MMP14-selective protease sequence to generate a
      binary, "switch-on" fluorescence reporter capable of measuring MMP14 location,
      activity, and temporal dynamics. The MMP14-fluorogen activating protein biosensor
      approach is applicable to both short and long-term imaging modalities and
      contains an adaptable module that can be used to study many membrane-bound
      proteases. This MMP14 biosensor promises to serve as a tool for the advancement
      of a broad range of investigations targeting MMP14 activity during cell migration
      in health and disease.

PMID- 29651045
TI  - Dissolved organic carbon leaching from plastics stimulates microbial activity in
      the ocean.
AB  - Approximately 5.25 trillion plastic pieces are floating at the sea surface. The
      impact of plastic pollution on the lowest trophic levels of the food web,
      however, remains unknown. Here we show that plastics release dissolved organic
      carbon (DOC) into the ambient seawater stimulating the activity of heterotrophic
      microbes. Our estimates indicate that globally up to 23,600 metric tons of DOC
      are leaching from marine plastics annually. About 60% of it is available to
      microbial utilization in less than 5 days. If exposed to solar radiation,
      however, this DOC becomes less labile. Thus, plastic pollution of marine surface
      waters likely alters the composition and activity of the base of the marine food
      webs. It is predicted that plastic waste entering the ocean will increase by a
      factor of ten within the next decade, resulting in an increase in plastic-derived
      DOC that might have unaccounted consequences for marine microbes and for the
      ocean system.

PMID- 29651046
TI  - Understanding physical (in-) activity, overweight, and obesity in childhood:
      Effects of congruence between physical self-concept and motor competence.
AB  - Both the physical self-concept and actual motor competence are important for
      healthy future physical activity levels and consequently decrease overweight and
      obesity in childhood. However, children scoring high on motor competence do not
      necessarily report high levels of physical self-concept and vice versa, resulting
      in respective (in-) accuracy also referred to as (non-) veridicality. This study
      examines whether children's accuracy of physical self-concept is a meaningful
      predictive factor for their future physical activity. Motor competence, physical
      self-concept and physical activity were assessed in 3rd grade and one year later
      in 4th grade. Children's weight status was categorized based on WHO
      recommendations. Polynomial regression with Response surface analyses were
      conducted with a quasi-DIF approach examining moderating weight status effects.
      Analyses revealed that children with higher motor competence levels and higher
      self-perceptions show greater physical activity. Importantly, children who
      perceive their motor competence more accurately (compared to less) show more
      future physical activity. This effect is strong for underweight and
      overweight/obese children, but weak for normal weight children. This study
      indicates that an accurate self-perception of motor competence fosters future
      physical activity beyond single main effects, respectively. Hence, the promotion
      of actual motor competence should be linked with the respective development of
      accurate self-knowledge.

PMID- 29651047
TI  - Perturbation of the yeast mitochondrial lipidome and associated membrane proteins
      following heterologous expression of Artemia-ANT.
AB  - Heterologous expression is a landmark technique for studying a protein itself or
      its effect on the expression host, in which membrane-embedded proteins are a
      common choice. Yet, the impact of inserting a foreign protein to the lipid
      environment of host membranes, has never been addressed. Here we demonstrated
      that heterologous expression of the Artemia franciscana adenine nucleotide
      translocase (ANT) in yeasts altered lipidomic composition of their inner
      mitochondrial membranes. Along with this, activities of complex II, IV and ATP
      synthase, all membrane-embedded components, were significantly decreased while
      their expression levels remained unaffected. Although the results represent an
      individual case of expressing a crustacean protein in yeast inner mitochondrial
      membranes, it cannot be excluded that host lipidome alterations is a more
      widespread epiphenomenon, potentially biasing heterologous expression
      experiments. Finally, our results raise the possibility that not only lipids
      modulate protein function, but also membrane-embedded proteins modulate lipid
      composition, thus revealing a reciprocal mode of regulation for these two
      biomolecular entities.

PMID- 29651048
TI  - Emotion and anxiety potentiate the way attention alters visual appearance.
AB  - The ability to swiftly detect and prioritize the processing of relevant
      information around us is critical for the way we interact with our environment.
      Selective attention is a key mechanism that serves this purpose, improving
      performance in numerous visual tasks. Reflexively attending to sudden information
      helps detect impeding threat or danger, a possible reason why emotion modulates
      the way selective attention affects perception. For instance, the sudden
      appearance of a fearful face potentiates the effects of exogenous (involuntary,
      stimulus-driven) attention on performance. Internal states such as trait anxiety
      can also modulate the impact of attention on early visual processing. However,
      attention does not only improve performance; it also alters the way visual
      information appears to us, e.g. by enhancing perceived contrast. Here we show
      that emotion potentiates the effects of exogenous attention on both performance
      and perceived contrast. Moreover, we found that trait anxiety mediates these
      effects, with stronger influences of attention and emotion in anxious observers.
      Finally, changes in performance and appearance correlated with each other, likely
      reflecting common attentional modulations. Altogether, our findings show that
      emotion and anxiety interact with selective attention to truly alter how we see.

PMID- 29651050
TI  - Drought and plant neighbourhood interactively determine herbivore consumption and
      performance.
AB  - Both plant neighbourhood composition and drought have well-known independent
      effects on insect herbivore performance, but their interactive effects remain
      elusive. In this study we performed a laboratory experiment to investigate the
      independent and combined effects of plant neighbourhood composition and drought
      on the performance of Gypsy moth larvae (Lymantria dispar) feeding on silver
      birch (Betula pendula) leaves. For this, we collected leaf samples from birch
      trees growing in a field experiment where we manipulated both host-tree species
      diversity (three levels: birch monocultures, two-species mixtures associating
      birch with the pedunculate oak Quercus robur or maritime pine Pinus pinaster, and
      three-species mixture with pedunculate oak, the maritime pine and birch) and
      water availability (two levels: irrigated vs. non-irrigated). In most cases,
      plant neighbourhood composition and irrigation treatments independently and
      interactively affected herbivore performance traits, especially those related to
      growth and food (i.e. birch leaves) processing. By addressing the interactive
      effects of tree species diversity and drought on insect herbivory from the
      herbivore's point of view, our study builds toward a better understanding of the
      multiple ecological drivers of plant-insect interactions.

PMID- 29651049
TI  - GABAergic inhibition in dual-transmission cholinergic and GABAergic striatal
      interneurons is abolished in Parkinson disease.
AB  - We report that half striatal cholinergic interneurons are dual transmitter
      cholinergic and GABAergic interneurons (CGINs) expressing ChAT, GAD65, Lhx7, and
      Lhx6 mRNAs, labeled with GAD and VGAT, generating monosynaptic dual
      cholinergic/GABAergic currents and an inhibitory pause response. Dopamine
      deprivation increases CGINs ongoing activity and abolishes GABAergic inhibition
      including the cortico-striatal pause because of high [Cl-]i levels. Dopamine
      deprivation also dramatically increases CGINs dendritic arbors and monosynaptic
      interconnections probability, suggesting the formation of a dense CGINs network.
      The NKCC1 chloride importer antagonist bumetanide, which reduces [Cl-]i levels,
      restores GABAergic inhibition, the cortico-striatal pause-rebound response, and
      attenuates motor effects of dopamine deprivation. Therefore, most of the striatal
      cholinergic excitatory drive is balanced by a concomitant powerful GABAergic
      inhibition that is impaired by dopamine deprivation. The attenuation by
      bumetanide of cardinal features of Parkinson's disease paves the way to a novel
      therapeutic strategy based on a restoration of low [Cl-]i levels and GABAergic
      inhibition.

PMID- 29651051
TI  - Collagen IV-conveyed signals can regulate chemokine production and promote liver
      metastasis.
AB  - Liver metastases remain a major cause of death from gastrointestinal tract
      cancers as well as from other malignancies such as breast and lung carcinomas and
      melanoma. Understanding the underlying biology is essential for the design of
      effective targeted therapies. We previously reported that collagen IV
      alpha1/alpha2 overexpression in non-metastatic lung carcinoma (M27colIV) cells
      increased their metastatic ability, specifically to the liver and documented high
      collagen IV levels in surgical resections of liver metastases from diverse tumor
      types. Here, we aimed to elucidate the functional relevance of collagen IV to
      metastatic outgrowth in the liver. Gene expression profiling revealed in
      M27colIVcells significant increases in the expression of chemokines CCL5 (5.7
      fold) and CCL7 (2.6-fold) relative to wild-type cells, and this was validated by
      qPCR and western blotting. Similarly, in human colon carcinoma KM12C and KM12SM
      cells with divergent liver-colonizing potentials, CCL7 and CCL5 production
      correlated with type IV collagen expression and the metastatic phenotype. CCL7
      silencing by short hairpin RNA (shRNA) reduced experimental liver metastasis in
      both cell types, whereas CCL5 silencing reduced metastasis of M27colIV cells,
      implicating these cytokines in metastatic expansion in the liver. Subsequent
      functional analyses implicated both MEK/ERK and PI3K signaling upstream of CCL7
      upregulation and identified CCL7 (but not CCL5) as a critical migration/invasion
      factor, acting via the chemokine receptor CCR3. Chemokine CCL5 was identified as
      a regulator of the T-cell immune response in the liver. Loss of CCL7 in KM12SM
      cells was also associated with altered E-cadherin and reduced vimentin and Snail
      expression, implicating it in epithelial-to-mesenchymal transition in these
      cells. Moreover, in clinical specimens of colon cancer liver metastases analyzed
      by immunohistochemistry, CCL5 and CCL7 levels paralleled those of collagen IV.
      The results identify the chemokines CCL5 and CCL7 as type IV collagen-regulated
      genes that promote liver metastasis by distinct and complementary mechanisms.

PMID- 29651052
TI  - Management of glycemic variation in diabetic patients receiving parenteral
      nutrition by continuous subcutaneous insulin infusion (CSII) therapy.
AB  - To compare the continuous subcutaneous insulin infusion (CSII) or insulin
      glargine based multiple injections (MDI) therapy on glycemic variations in
      diabetic patients receiving PN outside of intensive care settings. This was a
      single-center, randomized, open-label trial. Patients with type 2 diabetes (T2D)
      who were receiving parenteral nutrition (PN) were recruited. After baseline data
      were collected, recruited patients were then randomized 1:1 to a CSII group or a
      MDI group. All patients were subjected to a 4-day retrospective Continuous
      Glucose Monitoring (CGM). The primary endpoint was the differences of the 24-hrs
      mean amplitude of glycemic excursion (MAGE) in patients receiving the PN therapy
      between the two groups. A total of 102 patients with T2D receiving PN were
      recruited. Patients in the CSII group had a significantly decreased mean glucose
      level (MBG), the standard deviation of MG (SDBG), MAGE, and the coefficient of
      variation (CV%) compared to those in MDI group (all P < 0.01). Furthermore, we
      found that the patients who received a bolus insulin dose required maintaining
      euglycemic control was gradually decreased during the PN period in both groups at
      the endpoint. The administration of insulin via CSII led to a significant
      decrease in glycemic variations in patients receiving PN.

PMID- 29651053
TI  - Targeted in situ genome-wide profiling with high efficiency for low cell numbers.
AB  - Cleavage under targets and release using nuclease (CUT&RUN) is an epigenomic
      profiling strategy in which antibody-targeted controlled cleavage by micrococcal
      nuclease releases specific protein-DNA complexes into the supernatant for paired
      end DNA sequencing. As only the targeted fragments enter into solution, and the
      vast majority of DNA is left behind, CUT&RUN has exceptionally low background
      levels. CUT&RUN outperforms the most widely used chromatin immunoprecipitation
      (ChIP) protocols in resolution, signal-to-noise ratio and depth of sequencing
      required. In contrast to ChIP, CUT&RUN is free of solubility and DNA
      accessibility artifacts and has been used to profile insoluble chromatin and to
      detect long-range 3D contacts without cross-linking. Here, we present an improved
      CUT&RUN protocol that does not require isolation of nuclei and provides high
      quality data when starting with only 100 cells for a histone modification and
      1,000 cells for a transcription factor. From cells to purified DNA, CUT&RUN
      requires less than a day at the laboratory bench and requires no specialized
      skills.

PMID- 29651055
TI  - Incorporation of isotopic, fluorescent, and heavy-atom-modified nucleotides into
      RNAs by position-selective labeling of RNA.
AB  - Site-specific incorporation of labeled nucleotides is an extremely useful
      synthetic tool for many structural studies (e.g., NMR, electron paramagnetic
      resonance (EPR), fluorescence resonance energy transfer (FRET), and X-ray
      crystallography) of RNA. However, specific-position-labeled RNAs >60 nt are not
      commercially available on a milligram scale. Position-selective labeling of RNA
      (PLOR) has been applied to prepare large RNAs labeled at desired positions, and
      all the required reagents are commercially available. Here, we present a step-by
      step protocol for the solid-liquid hybrid phase method PLOR to synthesize 71-nt
      RNA samples with three different modification applications, containing (i) a
      13C15N-labeled segment; (ii) discrete residues modified with Cy3, Cy5, or biotin;
      or (iii) two iodo-U residues. The flexible procedure enables a wide range of
      downstream biophysical analyses using precisely localized functionalized
      nucleotides. All three RNAs were obtained in <2 d, excluding time for preparing
      reagents and optimizing experimental conditions. With optimization, the protocol
      can be applied to other RNAs with various labeling schemes, such as ligation of
      segmentally labeled fragments.

PMID- 29651057
TI  - Device integrates with practice management software.

PMID- 29651054
TI  - Integrated design, execution, and analysis of arrayed and pooled CRISPR genome
      editing experiments.
AB  - CRISPR (clustered regularly interspaced short palindromic repeats) genome-editing
      experiments offer enormous potential for the evaluation of genomic loci using
      arrayed single guide RNAs (sgRNAs) or pooled sgRNA libraries. Numerous
      computational tools are available to help design sgRNAs with optimal on-target
      efficiency and minimal off-target potential. In addition, computational tools
      have been developed to analyze deep-sequencing data resulting from genome-editing
      experiments. However, these tools are typically developed in isolation and
      oftentimes are not readily translatable into laboratory-based experiments. Here,
      we present a protocol that describes in detail both the computational and
      benchtop implementation of an arrayed and/or pooled CRISPR genome-editing
      experiment. This protocol provides instructions for sgRNA design with CRISPOR
      (computational tool for the design, evaluation, and cloning of sgRNA sequences),
      experimental implementation, and analysis of the resulting high-throughput
      sequencing data with CRISPResso (computational tool for analysis of genome
      editing outcomes from deep-sequencing data). This protocol allows for design and
      execution of arrayed and pooled CRISPR experiments in 4-5 weeks by non-experts,
      as well as computational data analysis that can be performed in 1-2 d by both
      computational and noncomputational biologists alike using web-based and/or
      command-line versions.

PMID- 29651058
TI  - Google or your dentist?
AB  - Assessment of information resources for people with hypodontia 2018; 4: 18001
      http://dx.doi.org/10.1038/bdjopen.2018.1.

PMID- 29651056
TI  - Evidence of exposure of domestic pigs to Highly Pathogenic Avian Influenza H5N1
      in Nigeria.
AB  - Avian influenza viruses (AIV) potentially transmit to swine as shown by
      experiments, where further reassortment may contribute to the generation of
      pandemic strains. Associated risks of AIV inter-species transmission are greater
      in countries like Nigeria with recurrent epidemics of highly pathogenic AI (HPAI)
      in poultry and significant pig population. Analysis of 129 tracheal swab
      specimens collected from apparently healthy pigs at slaughterhouse during
      presence of HPAI virus H5N1 in poultry in Nigeria for influenza A by RT-qPCR
      yielded 43 positive samples. Twenty-two could be determined by clade specific RT
      qPCR as belonging to the H5N1 clade 2.3.2.1c and confirmed by partial
      hemagglutinin (HA) sequence analysis. In addition, 500 swine sera were screened
      for antibodies against influenza A virus nucleoprotein and H5 HA using
      competition ELISAs and hemagglutination inhibition (HI) tests. Serologically, 222
      (44.4%) and 42 (8.4%) sera were positive for influenza A virus NP and H5
      antibodies, respectively. Sera reacted to H5N1 and A/H1N1pdm09 strains by HI
      suggesting exposure of the Nigerian domestic pig population to these viruses. We
      report for the first time in Nigeria, exposure of domestic pigs to H5N1 virus.
      This poses potential public health and pandemic risk due to interspecies
      transmission of avian and human influenza viruses.

PMID- 29651059
TI  - Aesthetic possibilities in removable prosthodontics. Part 3: Photometric tooth
      selection, tooth setting, try-in, fitting, reviewing and trouble-shooting.
AB  - This final article in a series of three on producing complete dentures which the
      patient considers attractive, describes selecting the denture teeth, setting the
      front teeth at the chairside, the try-in visits, processing, fitting and
      reviewing the dentures. The role of the patient as captain of the ship, the
      dental nurse as the patient's support and liaison officer, and the clinician as
      the first technical officer is outlined. The use of immediate replay video
      technology in allowing a patient to see what the trial denture really looks like
      is described. It is vital that the patient is completely happy with its
      appearance in every detail before any denture is finished. Dealing with post
      fitting aesthetic problems is considered.

PMID- 29651060
TI  - BAD SCIENCE: Oil pulling.

PMID- 29651062
TI  - Layering composites just got easier.

PMID- 29651061
TI  - Start your career in implant dentistry.

PMID- 29651063
TI  - Environmental issues: Dental sustainability.

PMID- 29651065
TI  - A sustainable, fish-friendly toothbrush.

PMID- 29651064
TI  - We need to eat less sugar - but how?
AB  - Factors related to reducing free sugar intake among white ethnic adults in the
      UK: a qualitative study 2018; 4: 17024 http://dx.doi.org/10.1038/bdjopen.2017.24.

PMID- 29651066
TI  - An unparalleled digital experience.

PMID- 29651068
TI  - Time capsule sealed in new ENT and dental hospital building.

PMID- 29651067
TI  - Prosthetic Dentistry Department reunion planned.

PMID- 29651069
TI  - OMFS: Instant relief.

PMID- 29651070
TI  - BDA Branch AGM Notices.

PMID- 29651071
TI  - The new place to go for all things dental.

PMID- 29651073
TI  - Flexible payment plans launched.

PMID- 29651074
TI  - Scaling new heights in patient care.

PMID- 29651075
TI  - Quicker, easier posterior restorations.

PMID- 29651076
TI  - Martin Downer.

PMID- 29651077
TI  - New BDA member events.

PMID- 29651078
TI  - Competence, competency-based education and undergraduate dental education: a
      discussion paper.
AB  - The competence of dental educators is as important as the competence of dental
      graduates.

PMID- 29651080
TI  - DENTISTS ON FILM: Lethal Weapon 4.

PMID- 29651079
TI  - A 'happy-air' alternative to general anaesthetic?
AB  - Does relative analgesia with nitrous oxide reduce the number of general
      anaesthetic sessions and dental loss? 2018; 224: 429-433
      http://dx.doi.org/10.1038/sj.bdj.2018.215.

PMID- 29651081
TI  - Flexible new plans.

PMID- 29651082
TI  - Christmas issue 2018 - call for content.

PMID- 29651083
TI  - Nature's own powerful, non-toxic disinfectant.

PMID- 29651086
TI  - Providing a dedicated service to dental practices.

PMID- 29651087
TI  - Data is or data are.

PMID- 29651088
TI  - Culture and its influence on dental education.
AB  - An understanding of the differences in European culture may benefit student
      learning.

PMID- 29651090
TI  - PERSPECTIVES: The dental recruitment crisis.

PMID- 29651089
TI  - Healthcare provision: Registration and retention of dentists.

PMID- 29651091
TI  - Special care dentistry: Advanced care planning.

PMID- 29651092
TI  - The first BDJ Clinician's Guide is published.

PMID- 29651093
TI  - Maxillary position.

PMID- 29651094
TI  - Drain away the pain.
AB  - Efficacy of first aid treatment of acute apical abscess in an NHS emergency
      clinic 2018; 224: 523-527 http://dx.doi.org/10.1038/sj.bdj.2018.xxx.

PMID- 29651096
TI  - #JawSurgery: Analysis of social media use in orthognathic surgery patients.

PMID- 29651095
TI  - Validation of ultrasound bioimaging to predict worm burden and treatment efficacy
      in preclinical filariasis drug screening models.
AB  - Filariasis is a global health problem targeted for elimination. Curative drugs
      (macrofilaricides) are required to accelerate elimination. Candidate
      macrofilaricides require testing in preclinical models of filariasis. The
      incidence of infection failures and high intra-group variation means that large
      group sizes are required for drug testing. Further, a lack of accurate,
      quantitative adult biomarkers results in protracted timeframes or multiple groups
      for endpoint analyses. Here we evaluate intra-vital ultrasonography (USG) to
      identify B. malayi in the peritonea of gerbils and CB.17 SCID mice and assess
      prognostic value in determining drug efficacy. USG operators, blinded to
      infection status, could detect intra-peritoneal filarial dance sign (ipFDS) with
      100% specificity and sensitivity, when >5 B. malayi worms were present in SCID
      mice. USG ipFDS was predictive of macrofilaricidal activity in randomized,
      blinded studies comparing flubendazole, albendazole and vehicle-treated SCID
      mice. Semi-quantification of ipFDS could predict worm burden >10 with 87-100%
      accuracy in SCID mice or gerbils. We estimate that pre-assessment of worm burden
      by USG could reduce intra-group variation, obviate the need for surgical
      implantations in gerbils, and reduce total SCID mouse use by 40%. Thus,
      implementation of USG may reduce animal use, refine endpoints and negate invasive
      techniques for assessing anti-filarial drug efficacy.

PMID- 29651098
TI  - Implantable cardioverter defibrillators in chronic kidney disease.

PMID- 29651097
TI  - Unraveling the compromised biomechanical performance of type 2 diabetes- and Roux
      en-Y gastric bypass bone by linking mechanical-structural and physico-chemical
      properties.
AB  - Type 2 diabetes mellitus (T2DM) is a metabolic disorder associated with obesity
      and hyperglycemia. Roux-en-Y gastric bypass (RYGB) surgery is a common treatment
      for severely obese patients and T2DM. Both RYGB and T2DM are linked to increased
      skeletal fragility, though the exact mechanisms are poorly understood. Our aim
      was to characterize the structural, mechanical and compositional properties of
      bones from diet-induced obese and RYGB-treated obese (bypass) mice to elucidate
      which the exact factors are contributing to the increased skeletal fragility. To
      achieve this, a combinatory approach including microfocus X-ray computed
      tomography, 3-point bending, finite element modeling and Raman spectroscopy, was
      used. Compared to aged-matched lean controls, the obese mice displayed decreased
      cortical thickness, trabecular bone loss, decreased stiffness and increased
      Young's modulus. For the bypass mice, these alterations were even more
      pronounced, and additionally they showed low mineral-to-matrix ratio in the
      cortical endosteal area. Accumulation of the advanced glycation end-product (AGE)
      pentosidine was found in the cortex of obese and bypass groups and this
      accumulation was correlated with an increased Young's modulus. In conclusion, we
      found that the increased fracture risk in T2DM- and post-RYGB bones is mainly
      driven by accumulation of AGEs and macro-structural alterations, generating
      biomechanical dysfunctionality.

PMID- 29651099
TI  - Author Correction: Disposition of a Glucose Load into Hepatic Glycogen by Direct
      and Indirect Pathways in Juvenile Seabass and Seabream.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 29651100
TI  - Transcriptomics: Finding structure in gene expression.

PMID- 29651101
TI  - Author Correction: Essential role of mitochondrial Stat3 in p38MAPK mediated
      apoptosis under oxidative stress.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 29651102
TI  - Exosomes from adipose-derived stem cells overexpressing Nrf2 accelerate cutaneous
      wound healing by promoting vascularization in a diabetic foot ulcer rat model.
AB  - Diabetic foot ulcers (DFU) increase the risks of infection and amputation in
      patients with diabetes mellitus (DM). The impaired function and senescence of
      endothelial progenitor cells (EPCs) and high glucose-induced ROS likely
      exacerbate DFUs. We assessed EPCs in 60 patients with DM in a hospital or primary
      care setting. We also evaluated the therapeutic effects of exosomes secreted from
      adipose-derived stem cells (ADSCs) on stress-mediated senescence of EPCs induced
      by high glucose. Additionally, the effects of exosomes and Nrf2 overexpression in
      ADSCs were investigated in vitro and in vivo in a diabetic rat model. We found
      that ADSCs that secreted exosomes promoted proliferation and angiopoiesis in EPCs
      in a high glucose environment and that overexpression of Nrf2 increased this
      protective effect. Wounds in the feet of diabetic rats had a significantly
      reduced ulcerated area when treated with exosomes from ADSCs overexpressing Nrf2.
      Increased granulation tissue formation, angiogenesis, and levels of growth factor
      expression as well as reduced levels of inflammation and oxidative stress-related
      proteins were detected in wound beds. Our data suggest that exosomes from ADSCs
      can potentially promote wound healing, particularly when overexpressing Nrf2 and
      therefore that the transplantation of exosomes may be suitable for clinical
      application in the treatment of DFUs.

PMID- 29651103
TI  - Versatile and efficient chromatin pull-down methodology based on DNA triple helix
      formation.
AB  - The goal of present paper is to develop a reliable DNA-based method for isolation
      of protein complexes bound to DNA (Isolation of DNA Associated Proteins: IDAP).
      We describe a robust and versatile procedure to pull-down chromatinized DNA
      sequences-of-interest by formation of a triple helix between a sequence tag
      present in the DNA and a complementary triple helix forming oligonucleotide (TFO)
      coupled to a desthiobiotin residue. Following optimization to insure efficient
      recovery of native plasmids via TFO probe in vitro, the procedure is shown to
      work under various experimental situations. For instance, it allows capture
      proteins associated to plasmids hosted in E. coli, and is also successfully
      applied to recovering nucleosomes in vitro opening many possibilities to study
      post translational modifications of histones in a genuine nucleosome context.
      Incubation in human nuclear extracts of a plasmid carrying a NF-kappaB model
      promoter is shown to pull-down a specific transcription factor. Finally,
      isolation of a specific locus from human genomic chromatin has been successfully
      achieved (Chromatin-of-Interest Fragment Isolation: CoIFI). In conclusion, the
      methodology can be implemented for capturing proteins that specifically bind to
      any sequence-of-interest, DNA adduct or secondary structure provided a short
      sequence tag for triple helix formation is located nearby.

PMID- 29651104
TI  - Author Correction: Glomerulocapillary miRNA response to HLA-class I antibody in
      vitro and in vivo.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 29651106
TI  - Senotherapeutics for healthy ageing.

PMID- 29651107
TI  - Circular RNA circ-4099 is induced by TNF-alpha and regulates ECM synthesis by
      blocking miR-616-5p inhibition of Sox9 in intervertebral disc degeneration.
AB  - Circular RNAs (circRNAs) play important roles in the initiation and development
      of different diseases. Here, we detected their role in intervertebral disc (IVD)
      degeneration. An Arraystar human circular RNA microarray assay was used to detect
      circRNAs in normal and degenerated human IVD nucleus pulposus (NP) tissues. The
      role of circ-4099 in IVDD and its mechanism were evaluated by qRT-PCR and gain-of
      function/loss-of-function studies. Interaction networks for competing endogenous
      RNAs (ceRNAs), miRNAs, and miRNA target gene were detected by bioinformatics
      analysis, RNA immunoprecipitation and luciferase assay. Expression of seventy-two
      circRNAs were increased by more than twofold in degenerated NP tissues. qRT-PCR
      showed that the expression of circ-4099 in NP tissues was consistent with that of
      the array screening. Over-expression of circ-4099 increased the expression of
      Collagen II and Aggrecan and decreased the secretion of the pro-inflammatory
      factors IL-1beta, TNF-alpha, and PGE2. TNF-alpha treatment increased circ-4099
      expression in NP cells. NF-kappaB/MAPK inhibitors or shRNAs abolished the
      inductive effects of TNF-alpha on circ-4099 expression. We further demonstrated
      that circ-4099 was able to function as a "sponge" by competitively binding miR
      616-5p, which reversed the suppression of Sox9 by miR-616-5p. We used DNA pull
      down and spectrometry experiments to show that TNF-alpha can promote circ-4099
      transcription through upregulation of GRP78. We provide the first evidence that
      shows circRNAs are differentially expressed in degenerated and normal NP tissues.
      Circ-4099 may play a role in a protective mechanism and be part of a compensatory
      response that maintains the synthesis and secretion of the extracellular matrix
      in NP cells and might be a protective factor in IVD degeneration as well as
      restore NP cell function.

PMID- 29651108
TI  - 3D artificial round section micro-vessels to investigate endothelial cells under
      physiological flow conditions.
AB  - In the context of xenotransplantation, in ischemia/reperfusion injury as well as
      in cardiovascular research, the study of the fascinating interplay between
      endothelial cells (EC) and the plasma cascade systems often requires in vitro
      models. Blood vessels are hardly reproducible with standard flat-bed culture
      systems and flow-plate assays are limited in their low surface-to-volume ratio
      which impedes the study of the anticoagulant properties of the endothelial cells.
      According to the 3R regulations (reduce, replace and refine animal
      experimentation) we developed a closed circuit microfluidic in vitro system in
      which endothelial cells are cultured in 3D round section microchannels and
      subjected to physiological, pulsatile flow. In this study, a 3D monolayer of
      porcine aortic EC was perfused with human serum to mimic a xenotransplantation
      setting. Complement as well as EC activation was assessed in the presence or
      absence of complement inhibitors showing the versatility of the model for drug
      testing. Complement activation products as well as E-selectin expression were
      detected and visualized in situ by high resolution confocal microscopy.
      Furthermore, porcine pro-inflammatory cytokines as well as soluble complement
      components in the recirculating fluid phase were detected after human serum
      perfusion providing a better overview of the artificial vascular environment.

PMID- 29651109
TI  - Author Correction: Non-invasive three-dimension control of light between turbid
      layers using a surface quasi-point light source for precorrection.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 29651105
TI  - Chemical probes and drug leads from advances in synthetic planning and
      methodology.
AB  - Screening of small-molecule libraries is a productive method for identifying both
      chemical probes of disease-related targets and potential starting points for drug
      discovery. In this article, we focus on strategies such as diversity-oriented
      synthesis that aim to explore novel areas of chemical space efficiently by
      populating small-molecule libraries with compounds containing structural features
      that are typically under-represented in commercially available screening
      collections. Drawing from more than a decade's worth of examples, we highlight
      how the design and synthesis of such libraries have been enabled by modern
      synthetic chemistry, and we illustrate the impact of the resultant chemical
      probes and drug leads in a wide range of diseases.

PMID- 29651110
TI  - Self-cleaning and surface chemical reactions during hafnium dioxide atomic layer
      deposition on indium arsenide.
AB  - Atomic layer deposition (ALD) enables the ultrathin high-quality oxide layers
      that are central to all modern metal-oxide-semiconductor circuits. Crucial to
      achieving superior device performance are the chemical reactions during the first
      deposition cycle, which could ultimately result in atomic-scale perfection of the
      semiconductor-oxide interface. Here, we directly observe the chemical reactions
      at the surface during the first cycle of hafnium dioxide deposition on indium
      arsenide under realistic synthesis conditions using photoelectron spectroscopy.
      We find that the widely used ligand exchange model of the ALD process for the
      removal of native oxide on the semiconductor and the simultaneous formation of
      the first hafnium dioxide layer must be significantly revised. Our study provides
      substantial evidence that the efficiency of the self-cleaning process and the
      quality of the resulting semiconductor-oxide interface can be controlled by the
      molecular adsorption process of the ALD precursors, rather than the subsequent
      oxide formation.

PMID- 29651111
TI  - Author Correction: Natural Erosion of Sandstone as Shape Optimisation.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 29651112
TI  - Behavioural medicine and gastrointestinal disorders: the promise of positive
      psychology.
AB  - Psychosocial risk factors linked to brain-gut dysregulation are prevalent across
      the spectrum of gastrointestinal disorders and are associated with poor patient
      outcomes. Robust and reproducible data in the areas of behavioural intervention
      science and the brain-gut axis have led to major advances in patient care,
      including the routine use of brain-gut psychotherapies to manage digestive
      symptoms and optimize coping. The logical next step for the emerging field of
      psychogastroenterology is to develop a scientific framework that enables the
      identification of those individual characteristics and coping styles that buffer
      patients against the negative psychological effects of chronic gastrointestinal
      disorders. A shift towards a strength-based, positive psychological science of
      gastrointestinal disorders could facilitate the integration of early, effective
      psychological care into gastroenterology practice. In this Perspective, I discuss
      the potential role of three human strengths with relevance to gastrointestinal
      health - resilience, optimism and self-regulation - and how these three
      constructs can be cultivated through existing or emerging brain-gut
      psychotherapies.

PMID- 29651113
TI  - Endogenous reference RNAs for microRNA quantitation in formalin-fixed, paraffin
      embedded lymph node tissue.
AB  - Lymph node metastasis is one of the most important factors for tumor
      dissemination. Quantifying microRNA (miRNA) expression using real-time PCR in
      formalin-fixed, paraffin-embedded (FFPE) lymph node can provide valuable
      information regarding the biological research for cancer metastasis. However, a
      universal endogenous reference gene has not been identified in FFPE lymph node.
      This study aimed to identify suitable endogenous reference genes for miRNA
      expression analysis in FFPE lymph node. FFPE lymph nodes were obtained from 41
      metastatic cancer and from 16 non-cancerous tissues. We selected 10 miRNAs as
      endogenous reference gene candidates using the global mean method. The stability
      of candidate genes was assessed by the following four statistical tools:
      BestKeeper, geNorm, NormFinder, and the comparative DeltaCt method. miR-103a was
      the most stable gene among candidate genes. However, the use of a single miR-103a
      was not recommended because its stability value exceeded the reference value.
      Thus, we combined stable genes and investigated the stability and the effect of
      gene normalization. The combination of miR-24, miR-103a, and let-7a was
      identified as one of the most stable sets of endogenous reference genes for
      normalization in FFPE lymph node. This study may provide a basis for miRNA
      expression analysis in FFPE lymph node tissue.

PMID- 29651115
TI  - Discovery of the World's Smallest Terrestrial Pteridophyte.
AB  - Ophioglossum L. commonly known as "adder's tongue fern", has been of great
      interest due to the highest number of chromosomes in any organism so far known in
      biological world. Here, a new species of adder's tongue fern has been discovered
      and reported from Western Ghats of India. It is prominently distinct from the
      other known taxa in Ophioglossaceae family. Phylogenetic analysis of three
      chloroplast DNA (cpDNA) regions (trnL-F, rbcL and psbA-trnH) unambiguously
      designate this adder's tongue fern as the distinct lineage and is sister to the
      clade containing O. parvifolium and O. nudicaule. Azolla caroliniana - an aquatic
      fern (average size, 0.5-1.5 cm), is the smallest fern on the earth. Our discovery
      discloses a new species of adder's tongue fern and ranking it among the smallest
      terrestrial fern in the world, attaining an average size of only 1-1.2 cm.

PMID- 29651114
TI  - A mechanistic framework for auxin dependent Arabidopsis root hair elongation to
      low external phosphate.
AB  - Phosphate (P) is an essential macronutrient for plant growth. Roots employ
      adaptive mechanisms to forage for P in soil. Root hair elongation is particularly
      important since P is immobile. Here we report that auxin plays a critical role
      promoting root hair growth in Arabidopsis in response to low external P. Mutants
      disrupting auxin synthesis (taa1) and transport (aux1) attenuate the low P root
      hair response. Conversely, targeting AUX1 expression in lateral root cap and
      epidermal cells rescues this low P response in aux1. Hence auxin transport from
      the root apex to differentiation zone promotes auxin-dependent hair response to
      low P. Low external P results in induction of root hair expressed auxin-inducible
      transcription factors ARF19, RSL2, and RSL4. Mutants lacking these genes disrupt
      the low P root hair response. We conclude auxin synthesis, transport and response
      pathway components play critical roles regulating this low P root adaptive
      response.

PMID- 29651116
TI  - Angular flux creep contributions in YBa2Cu3O7-delta nanocomposites from
      electrical transport measurements.
AB  - The shape of the electric-field-current-density (E-J) curve is determined by flux
      pinning and also by dynamics of vortices. Here, we propose a novel methodology to
      study the normalized flux creep rate S in YBa2Cu3O7-delta measured from E-J
      curves obtained by electrical transport measurements that provides a fast and
      versatile way to foresee the flux magnetic relaxation in films and disentangle
      angular flux creep contributions by the scaling of the isotropic contribution of
      S. After a detailed comparison of various pristine and nanocomposite films with
      differentiated nanostructures, we focus on the roles that intrinsic pinning and
      stacking faults (YBa2Cu4O8-intergrowths) play when the magnetic field is applied
      parallel to the superconducting CuO2 planes. This study reveals that the emerging
      intergrowths provide advanced pinning properties that additionally reduce the
      thermal activated flux magnetic relaxation. For this purpose, creep analysis
      becomes a very appropriate tool to elucidate the dominance of the different
      pinning sites at different regions of the magnetic-field-temperature diagram.

PMID- 29651118
TI  - Myositis: Are autoantibodies pathogenic in necrotizing myopathy?

PMID- 29651117
TI  - Field validation of recombinant antigen immunoassays for diagnosis of Lassa
      fever.
AB  - Lassa fever, a hemorrhagic fever caused by Lassa virus (LASV), is endemic in West
      Africa. It is difficult to distinguish febrile illnesses that are common in West
      Africa from Lassa fever based solely on a patient's clinical presentation. The
      field performance of recombinant antigen-based Lassa fever immunoassays was
      compared to that of quantitative polymerase chain assays (qPCRs) using samples
      from subjects meeting the case definition of Lassa fever presenting to Kenema
      Government Hospital in Sierra Leone. The recombinant Lassa virus (ReLASV) enzyme
      linked immunosorbant assay (ELISA) for detection of viral antigen in blood
      performed with 95% sensitivity and 97% specificity using a diagnostic standard
      that combined results of the immunoassays and qPCR. The ReLASV rapid diagnostic
      test (RDT), a lateral flow immunoassay based on paired monoclonal antibodies to
      the Josiah strain of LASV (lineage IV), performed with 90% sensitivity and 100%
      specificity. ReLASV immunoassays performed better than the most robust qPCR
      currently available, which had 82% sensitivity and 95% specificity. The
      performance characteristics of recombinant antigen-based Lassa virus immunoassays
      indicate that they can aid in the diagnosis of LASV Infection and inform the
      clinical management of Lassa fever patients.

PMID- 29651120
TI  - Myositis: Prognostic factors in 'pneumo-myositis'.

PMID- 29651119
TI  - Update on outcome assessment in myositis.
AB  - The adult and juvenile myositis syndromes, commonly referred to collectively as
      idiopathic inflammatory myopathies (IIMs), are systemic autoimmune diseases with
      the hallmarks of muscle weakness and inflammation. Validated, well-standardized
      measures to assess disease activity, known as core set measures, were developed
      by international networks of myositis researchers for use in clinical trials.
      Composite response criteria using weighted changes in the core set measures of
      disease activity were developed and validated for adult and juvenile patients
      with dermatomyositis and adult patients with polymyositis, with different
      thresholds for minimal, moderate and major improvement in adults and juveniles.
      Additional measures of muscle strength and function are being validated to
      improve content validity and sensitivity to change. A health-related quality of
      life measure, which incorporates patient input, is being developed for adult
      patients with IIM. Disease state criteria, including criteria for inactive
      disease and remission, are being used as secondary end points in clinical trials.
      MRI of muscle and immunological biomarkers are promising approaches to
      discriminate between disease activity and damage and might provide much-needed
      objective outcome measures. These advances in the assessment of outcomes for
      myositis treatment, along with collaborations between international networks,
      should facilitate further development of new therapies for patients with IIM.

PMID- 29651121
TI  - Classification of myositis.
AB  - The idiopathic inflammatory myopathies (IIMs; also known as myositis) are a
      heterogeneous group of disorders in which a common feature is chronic
      inflammation of skeletal muscle, leading to muscle weakness. Other organs are
      frequently affected in IIMs, such as the skin, joints, lungs, gastrointestinal
      tract and heart, contributing to morbidity and mortality. Currently, IIMs are
      most often subclassified into polymyositis, dermatomyositis and inclusion body
      myositis, but this subclassification has limitations as these subgroups often
      have overlapping clinical and histopathological features, and outcomes vary
      within the subgroups; additionally, subgroups without considerable myopathy are
      not included. A new way of subgrouping patients could be on the basis of the
      presence of myositis-specific autoantibodies. These autoantibodies are associated
      with distinct clinical features and, moreover, can help to identify subsets of
      IIMs in which extramuscular symptoms, such as skin manifestations, arthritis or
      interstitial lung disease, might be the presenting or predominant feature when
      muscle symptoms are mild or absent. The recognition that subphenotypes with
      single-organ involvement other than muscles exist is important for identifying
      patients with early disease, for clinical care demanding team management and in
      designing clinical studies to improve our understanding of this heterogeneous
      disease to develop new therapies.

PMID- 29651123
TI  - Author Correction: Cascaded Kerr photon-blockade sources and applications in
      quantum key distribution.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 29651122
TI  - Metabarcoding analysis of strongylid nematode diversity in two sympatric primate
      species.
AB  - Strongylid nematodes in large terrestrial herbivores such as great apes, equids,
      elephants, and humans tend to occur in complex communities. However,
      identification of all species within strongylid communities using traditional
      methods based on coproscopy or single nematode amplification and sequencing is
      virtually impossible. High-throughput sequencing (HTS) technologies provide
      opportunities to generate large amounts of sequence data and enable analyses of
      samples containing a mixture of DNA from multiple species/genotypes. We designed
      and tested an HTS approach for strain-level identification of gastrointestinal
      strongylids using ITS-2 metabarcoding at the MiSeq Illumina platform in samples
      from two free-ranging non-human primate species inhabiting the same environment,
      but differing significantly in their host traits and ecology. Although we
      observed overlapping of particular haplotypes, overall the studied primate
      species differed in their strongylid nematode community composition. Using HTS,
      we revealed hidden diversity in the strongylid nematode communities in non-human
      primates, more than one haplotype was found in more than 90% of samples and
      coinfections of more than one putative species occurred in 80% of samples. In
      conclusion, the HTS approach on strongylid nematodes, preferably using fecal
      samples, represents a time and cost-efficient way of studying strongylid
      communities and provides a resolution superior to traditional approaches.

PMID- 29651124
TI  - The Effects of Sampling Location and Predictor Point Estimate Certainty on
      Posterior Support in Bayesian Phylogeographic Generalized Linear Models.
AB  - The use of generalized linear models in Bayesian phylogeography has enabled
      researchers to simultaneously reconstruct the spatiotemporal history of a virus
      and quantify the contribution of predictor variables to that process. However,
      little is known about the sensitivity of this method to the choice of the
      discrete state partition. Here we investigate this question by analyzing a data
      set containing 299 sequences of the West Nile virus envelope gene sampled in the
      United States and fifteen predictors aggregated at four spatial levels. We
      demonstrate that although the topology of the viral phylogenies was consistent
      across analyses, support for the predictors depended on the level of aggregation.
      In particular, we found that the variance of the predictor support metrics was
      minimized at the most precise level for several predictors and maximized at more
      sparse levels of aggregation. These results suggest that caution should be taken
      when partitioning a region into discrete locations to ensure that interpretable,
      reproducible posterior estimates are obtained. These results also demonstrate why
      researchers should use the most precise discrete states possible to minimize the
      posterior variance in such estimates and reveal what truly drives the diffusion
      of viruses.

PMID- 29651125
TI  - Genetic diversity and phylogenetic characteristics of Chinese Tibetan and Yi
      minority ethnic groups revealed by non-CODIS STR markers.
AB  - Non-CODIS STRs, with high polymorphism and allele frequency difference among
      ethnically and geographically different populations, play a crucial role in
      population genetics, molecular anthropology, and human forensics. In this work,
      332 unrelated individuals from Sichuan Province (237 Tibetan individuals and 95
      Yi individuals) are firstly genotyped with 21 non-CODIS autosomal STRs, and
      phylogenetic relationships with 26 previously investigated populations (9,444
      individuals) are subsequently explored. In the Sichuan Tibetan and Yi, the
      combined power of discrimination (CPD) values are 0.9999999999999999999 and
      0.9999999999999999993, and the combined power of exclusion (CPE) values are 0.
      999997 and 0.999999, respectively. Analysis of molecular variance (AMOVA),
      principal component analysis (PCA), multidimensional scaling plots (MDS) and
      phylogenetic analysis demonstrated that Sichuan Tibetan has a close genetic
      relationship with Tibet Tibetan, and Sichuan Yi has a genetic affinity with
      Yunnan Bai group. Furthermore, significant genetic differences have widely
      existed between Chinese minorities (most prominently for Tibetan and Kazakh) and
      Han groups, but no population stratifications rather a homogenous group among Han
      populations distributed in Northern and Southern China are observed.
      Aforementioned results suggested that these 21 STRs are highly polymorphic and
      informative in the Sichuan Tibetan and Yi, which are suitable for population
      genetics and forensic applications.

PMID- 29651126
TI  - Author Correction: An extinct vertebrate preserved by its living hybridogenetic
      descendant.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 29651128
TI  - Encorafenib - a new agent for advanced-stage disease.

PMID- 29651127
TI  - Testosterone Deficiency, Weakness, and Multimorbidity in Men.
AB  - The purposes of this study were to evaluate the association between total
      testosterone (TT) deficiency and weakness on multimorbidity in men. Analyses were
      performed to examine the prevalence of multimobidity among young, middle-aged,
      and older men, with and without testosterone deficiency. Multivariate logistic
      models were also used to determine the association between age-specific TT
      tertiles and multimorbidity, adjusting for key sociodemographic variables, as
      well as a secondary analysis adjusted for grip strength. Multimorbidity was more
      prevalent among men with testosterone deficiency, compared to normal TT in the
      entire group (36.6% vs 55.2%; p < 0.001); however, differences were only seen
      within young (testosterone deficiency: 36.4%; normal TT: 13.5%; p < 0.001) and
      older men (testosterone deficiency: 75.0%; normal TT: 61.5%; p < 0.001). Robust
      associations were found between the age-specific low-TT (OR: 2.87; 95%CI: 2.14
      3.83) and moderate-TT (OR: 1.67; 95%CI: 1.27-2.20) tertiles (reference high-TT)
      and multimorbidity. Secondary analysis demonstrated that both low TT (OR: 1.82;
      95%CI: 1.29-2.55) and moderate-TT (OR: 1.31; 95%CI: 1.01-1.69) were associated
      with multimorbidity, even after adjusting for obesity (OR: 1.75; 95%CI: 1.07
      2.87) and NGS (OR: 1.21 per 0.05 unit lower NGS). Low TT and weakness in men were
      independently associated with multimorbidity at all ages; however, multimorbidity
      was more prevalent among young and older men with testosterone deficiency.

PMID- 29651129
TI  - Venetoclax-rituximab holds substantial promise in CLL.

PMID- 29651132
TI  - Compositional characteristics of human peripheral TRBV pseudogene rearrangements.
AB  - The diversity of the T cell receptor (TCR) complementarity determining region 3
      (CDR3) repertoire is the result of random combinations, insertions and deletions
      during recombination of the germline V, D and J gene fragments. During evolution,
      some human TCR beta chain variable (TRBV) pseudogenes have been retained. Many
      previous studies have focused on functional TRBV genes, while little attention
      has been given to TRBV pseudogenes. To describe the compositional characteristics
      of TRBV pseudogene rearrangements, we compared and analysed TRBV pseudogenes,
      TRBV open reading frames (ORFs) and functional TRBV genes via high-throughput
      sequencing of DNA obtained from the peripheral blood of 4 healthy volunteers and
      4 patients. Our results revealed several differences in J and D gene usage. The V
      deletion distribution profile of the pseudogenes was significantly different from
      that of the ORFs and functional genes. In addition, arginine, lysine and cysteine
      were more frequently used in putative CDR3 pseudogene rearrangements, while
      functional rearrangements used more leucine. This study presents a comprehensive
      description of the compositional characteristics of peripheral TRBV pseudogene
      rearrangements, which will provide a reference for further research on TRBV
      pseudogenes.

PMID- 29651131
TI  - Low-level mitochondrial heteroplasmy modulates DNA replication, glucose
      metabolism and lifespan in mice.
AB  - Mutations in mitochondrial DNA (mtDNA) lead to heteroplasmy, i.e., the
      intracellular coexistence of wild-type and mutant mtDNA strands, which impact a
      wide spectrum of diseases but also physiological processes, including endurance
      exercise performance in athletes. However, the phenotypic consequences of limited
      levels of naturally arising heteroplasmy have not been experimentally studied to
      date. We hence generated a conplastic mouse strain carrying the mitochondrial
      genome of an AKR/J mouse strain (B6-mtAKR) in a C57BL/6 J nuclear genomic
      background, leading to >20% heteroplasmy in the origin of light-strand DNA
      replication (OriL). These conplastic mice demonstrate a shorter lifespan as well
      as dysregulation of multiple metabolic pathways, culminating in impaired glucose
      metabolism, compared to that of wild-type C57BL/6 J mice carrying lower levels of
      heteroplasmy. Our results indicate that physiologically relevant differences in
      mtDNA heteroplasmy levels at a single, functionally important site impair the
      metabolic health and lifespan in mice.

PMID- 29651133
TI  - Refined protocols of tamoxifen injection for inducible DNA recombination in mouse
      astroglia.
AB  - Inducible DNA recombination of floxed alleles in vivo by liver metabolites of
      tamoxifen (TAM) is an important tool to study gene functions. Here, we describe
      protocols for optimal DNA recombination in astrocytes, based on the GLAST
      CreERT2/loxP system. In addition, we demonstrate that quantification of genomic
      recombination allows to determine the proportion of cell types in various brain
      regions. We analyzed the presence and clearance of TAM and its metabolites (N
      desmethyl-tamoxifen, 4-hydroxytamoxifen and endoxifen) in brain and serum of mice
      by liquid chromatographic-high resolution-tandem mass spectrometry (LC-HR-MS/MS)
      and assessed optimal injection protocols by quantitative RT-PCR of several floxed
      target genes (p2ry1, gria1, gabbr1 and Rosa26-tdTomato locus). Maximal
      recombination could be achieved in cortex and cerebellum by single daily
      injections for five and three consecutive days, respectively. Furthermore,
      quantifying the loss of floxed alleles predicted the percentage of GLAST-positive
      cells (astroglia) per brain region. We found that astrocytes contributed 20 to
      30% of the total cell number in cortex, hippocampus, brainstem and optic nerve,
      while in the cerebellum Bergmann glia, velate astrocytes and white matter
      astrocytes accounted only for 8% of all cells.

PMID- 29651134
TI  - Endothelial Cell Phenotypes are Maintained During Angiogenesis in Cultured
      Microvascular Networks.
AB  - A challenge in tissue engineering biomimetic models for studying angiogenesis is
      building the physiological complexity of real microvascular networks. Our
      laboratory recently introduced the rat mesentery culture model as an ex vivo
      experimental platform for investigating multicellular dynamics involved in
      angiogenesis within intact microvascular networks. The objective of this study
      was to compare endothelial cell phenotypes along capillary sprouts in cultured ex
      vivo rat mesentery microvascular networks to in vivo endothelial cell phenotypes.
      For Day 3 (Ex Vivo) tissues, adult rat mesentery tissues were cultured for three
      days in media supplemented with 10% serum. For Day 3 (In Vivo) tissues, adult
      rats were anesthetized and the mesentery was exteriorized for twenty minutes to
      induce angiogenesis. Microvascular networks from Day 3 (Ex Vivo) and Day 3 (In
      Vivo) groups were angiogenic, characterized by an increase in vessel density,
      capillary sprouting, and identification of similar BrdU-positive endothelial cell
      distributions along sprouts. Endothelial cells in both groups extended
      pseudopodia at the distal edge of capillary sprouts and displayed similar
      endothelial cell UNC5b, VEGFR-2, and CD36 labeling patterns. The results from
      this study support the physiological relevance of the rat mesentery culture model
      and highlight its novelty as a biomimetic tool for angiogenesis research.

PMID- 29651135
TI  - Author Correction: The Oncogenic Role of COL23A1 in Clear Cell Renal Cell
      Carcinoma.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 29651130
TI  - Targeting the tumour stroma to improve cancer therapy.
AB  - Cancers are not composed merely of cancer cells alone; instead, they are complex
      'ecosystems' comprising many different cell types and noncellular factors. The
      tumour stroma is a critical component of the tumour microenvironment, where it
      has crucial roles in tumour initiation, progression, and metastasis. Most
      anticancer therapies target cancer cells specifically, but the tumour stroma can
      promote the resistance of cancer cells to such therapies, eventually resulting in
      fatal disease. Therefore, novel treatment strategies should combine anticancer
      and antistromal agents. Herein, we provide an overview of the advances in
      understanding the complex cancer cell-tumour stroma interactions and discuss how
      this knowledge can result in more effective therapeutic strategies, which might
      ultimately improve patient outcomes.

PMID- 29651136
TI  - Local tissue manipulation via a force- and pressure-controlled AFM micropipette
      for analysis of cellular processes.
AB  - Local manipulation of complex tissues at the single-cell level is challenging and
      requires excellent sealing between the specimen and the micromanipulation device.
      Here, biological applications for a recently developed loading technique for a
      force- and pressure-controlled fluidic force microscope micropipette are
      described. This technique allows for the exact positioning and precise
      spatiotemporal control of liquid delivery. The feasibility of a local loading
      technique for tissue applications was investigated using two fluorescent dyes,
      with which local loading behaviour could be optically visualised. Thus,
      homogeneous intracellular distribution of CellTracker Red and accumulation of
      SYTO 9 Green within nuclei was realised in single cells of a tissue preparation.
      Subsequently, physiological micromanipulation experiments were performed.
      Salivary gland tissue was pre-incubated with the Ca2+-sensitive dye OGB-1. An
      intracellular Ca2+ rise was then initiated at the single-cell level by applying
      dopamine via micropipette. When pre-incubating tissue with the nitric oxide (NO)
      sensitive dye DAF-FM, NO release and intercellular NO diffusion was observed
      after local application of the NO donor SNP. Finally, local micromanipulation of
      a well-defined area along irregularly shaped cell surfaces of complex biosystems
      was shown for the first time for the fluidic force microscope micropipette. Thus,
      this technique is a promising tool for the investigation of the spatiotemporal
      effects of locally applied substances in complex tissues.

PMID- 29651137
TI  - Publisher Correction: Identification and characterization of the novel
      colonization factor CS30 based on whole genome sequencing in enterotoxigenic
      Escherichia coli (ETEC).
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 29651139
TI  - Publisher Correction: Electronic Properties of Synthetic Shrimp Pathogens-derived
      DNA Schottky Diodes.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 29651138
TI  - Gene expression links functional networks across cortex and striatum.
AB  - The human brain is comprised of a complex web of functional networks that link
      anatomically distinct regions. However, the biological mechanisms supporting
      network organization remain elusive, particularly across cortical and subcortical
      territories with vastly divergent cellular and molecular properties. Here, using
      human and primate brain transcriptional atlases, we demonstrate that spatial
      patterns of gene expression show strong correspondence with limbic and
      somato/motor cortico-striatal functional networks. Network-associated expression
      is consistent across independent human datasets and evolutionarily conserved in
      non-human primates. Genes preferentially expressed within the limbic network
      (encompassing nucleus accumbens, orbital/ventromedial prefrontal cortex, and
      temporal pole) relate to risk for psychiatric illness, chloride channel
      complexes, and markers of somatostatin neurons. Somato/motor associated genes are
      enriched for oligodendrocytes and markers of parvalbumin neurons. These analyses
      indicate that parallel cortico-striatal processing channels possess dissociable
      genetic signatures that recapitulate distributed functional networks, and
      nominate molecular mechanisms supporting cortico-striatal circuitry in health and
      disease.

PMID- 29651140
TI  - Novel Indole-fused benzo-oxazepines (IFBOs) inhibit invasion of hepatocellular
      carcinoma by targeting IL-6 mediated JAK2/STAT3 oncogenic signals.
AB  - Inspired by the well-documented tumor protecting ability of paullones, recently,
      we synthesized novel paullone-like scaffolds, indole-fused benzo-oxazepines
      (IFBOs), and screened them against hepatocellular carcinoma (HCC) specific Hep-G2
      cells. Three of the synthesized compounds significantly attenuated the
      progression of HCC in vitro. By computational studies, we further discovered that
      IFBOs exhibited a stable binding complex with the IL-6 receptor. In this context,
      we investigated in vivo study using the nitrosodiethyl amine (NDEA)-induced HCC
      model, which strengthened our previous findings by showing the blockade of the IL
      6 mediated JAK2/STAT3 oncogenic signaling pathway. Treatment with IFBOs showed
      remarkable attenuation of cellular proliferation, as evidenced through a decrease
      in the number of nodules, restoration of body weight, oxidative stress
      parameters, liver marker enzymes and histological architecture. Interestingly,
      using a metabolomic approach we further discovered that IFBOs can restore the
      perturbed metabolic profile associated with the HCC condition to normalcy.
      Particularly, the efficacy of compound 6a for an anti-HCC response was
      significantly better than the marketed chemotherapeutic drug, 5-fluorouracil.
      Altogether, these remarkable findings open up possibilities of developing IFBOs
      as novel future candidate molecules for plausible alternatives for HCC treatment.

PMID- 29651141
TI  - Defect-engineered TiO2 Hollow Spiny Nanocubes for Phenol Degradation under
      Visible Light Irradiation.
AB  - Herein, we mainly report a strategy for the facile synthesis of defect-engineered
      F-doped well-defined TiO2 hollow spiny nanocubes, constructed from NH4TiOF3 as
      precursor. The topological transformation of NH4TiOF3 mesocrystal is accompanied
      with fluorine anion releasing, which can be used as doping source to synthesize F
      doped TiO2. Our result shows that the introduction of oxygen vacancies (Vo's) and
      F dopant can be further achieved by a moderate photoreduction process. The as
      prepared sample is beneficial to improve photocatalystic degradation and
      Photoelectrochemical (PEC) efficiency under visible light irradiation. And this
      improvement in photocatalytic and photoelectrocatalytic performance can be
      ascribed to the significant enhancement of visible light absorption and
      separation of excited charges resulted from the presence of oxygen vacancies, F-
      ions and hollow structure of TiO2.

PMID- 29651142
TI  - Author Correction: Transitions from Ideal to Intermediate Cholesterol Levels may
      vary by Cholesterol Metric.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 29651143
TI  - Glycosylated piericidins from an endophytic streptomyces with cytotoxicity and
      antimicrobial activity.
AB  - Two new glycosylated piericidins, glucopiericidinol A3 (1) and 7-demethyl
      glucopiericidin A (2), along with four known analogs were isolated from the
      culture broth of Streptomyces sp. KIB-H1083. The chemical structures of new
      compounds were elucidated by spectroscopic analyses. Their cytotoxicity on HL-60,
      SMMC-772, A-549, MCF-7, and SW480 cell lines, as well as antimicrobial activities
      was evaluated. The results showed that glucopiericidin A (4) has potent
      cytotoxicity against HL-60, SMMC-772, A-549, and MCF-7 cell lines with IC50
      values of 0.34, 0.65, 0.60, and 0.50 MUM, respectively. For the antimicrobial
      activity, piericidin A (6) showed most powerful inhibitory activities against
      Xanthomonas oryzae pv. oryzicola, and Penicillium decumbens.

PMID- 29651144
TI  - Sirtuin 7 Deficiency Ameliorates Cisplatin-induced Acute Kidney Injury Through
      Regulation of the Inflammatory Response.
AB  - Cisplatin-induced acute kidney injury (AKI) has been recognized as one of
      cisplatin's serious side effects, limiting its use in cancer therapy. Sirtuin 1
      (SIRT1) and SIRT3 play protective roles against cisplatin-induced kidney injury.
      However, the role of SIRT7 in cisplatin-induced kidney injury is not yet known.
      In this study, we found that Sirt7 knockout (KO) mice were resistant to cisplatin
      induced AKI. Furthermore, our studies identified that loss of SIRT7 decreases the
      expression of tumor necrosis factor-alpha (TNF-alpha) by regulating the nuclear
      expression of the transcription factor nuclear factor kappa B. It has been
      reported that cisplatin-induced nephrotoxicity is mediated by TNF-alpha. Our
      results indicate that SIRT7 plays an important role in cisplatin-induced AKI and
      suggest the possibility of SIRT7 as a novel therapeutic target for cisplatin
      induced nephrotoxicity.

PMID- 29651145
TI  - Multicomponent reactions provide key molecules for secret communication.
AB  - A convenient and inherently more secure communication channel for encoding
      messages via specifically designed molecular keys is introduced by combining
      advanced encryption standard cryptography with molecular steganography. The
      necessary molecular keys require large structural diversity, thus suggesting the
      application of multicomponent reactions. Herein, the Ugi four-component reaction
      of perfluorinated acids is utilized to establish an exemplary database consisting
      of 130 commercially available components. Considering all permutations, this
      combinatorial approach can unambiguously provide 500,000 molecular keys in only
      one synthetic procedure per key. The molecular keys are transferred nondigitally
      and concealed by either adsorption onto paper, coffee, tea or sugar as well as by
      dissolution in a perfume or in blood. Re-isolation and purification from these
      disguises is simplified by the perfluorinated sidechains of the molecular keys.
      High resolution tandem mass spectrometry can unequivocally determine the
      molecular structure and thus the identity of the key for a subsequent decryption
      of an encoded message.

PMID- 29651146
TI  - High-resolution computed tomographic analysis of tooth replacement pattern of the
      basal neoceratopsian Liaoceratops yanzigouensis informs ceratopsian dental
      evolution.
AB  - The dental morphology and tooth replacement pattern of Liaoceratops
      yanzigouensis, the earliest known neoceratopsian, are important for our
      understanding of the evolution of the ceratopsian dental system. Here we describe
      the dental morphology and tooth replacement of Liaoceratops yanzigouensis based
      on high-resolution computed tomographic (CT) scan data of three specimens
      including the holotype, the first study for basal ceratopsian. The three
      dimensional reconstructions reveal some important new information, including:
      three teeth in the premaxilla in one side, two more teeth in the dentary than in
      the maxilla, incipiently developed mesial grooves on some crowns, two generations
      of replacement teeth within some tooth families; and most functional teeth were
      under heavy resorption by the replacement process, but still remained functional.
      Comparisons of tooth pair positions from opposite sides in the four jaw quadrants
      of three specimens revealed a degree of bilateral symmetry in replacement
      pattern. Reconstruction of Zahnreihen yields an avergae z-spacing of 2.58 with
      simultaneous front-to-back tooth replacement. Our study presents the earliest
      evidence of derived neoceratopsian traits of the complex dental batteries in
      ceratopsids. Most significantly, our models reveal the tracts of partially
      resorbed functional teeth which appears to track the growth of the jaws, traits
      previously undocumented in Ceratopsia.

PMID- 29651147
TI  - Response to climate change of montane herbaceous plants in the genus Rhodiola
      predicted by ecological niche modelling.
AB  - Climate change profoundly influences species distributions. These effects are
      evident in poleward latitudinal range shifts for many taxa, and upward
      altitudinal range shifts for alpine species, that resulted from increased annual
      global temperatures since the Last Glacial Maximum (LGM, ca. 22,000 BP). For the
      latter, the ultimate consequence of upward shifts may be extinction as species in
      the highest alpine ecosystems can migrate no further, a phenomenon often
      characterized as "nowhere to go". To predict responses to climate change of the
      alpine plants on the Qinghai-Tibetan Plateau (QTP), we used ecological niche
      modelling (ENM) to estimate the range shifts of 14 Rhodiola species, beginning
      with the Last Interglacial (ca. 120,000-140,000 BP) through to 2050.
      Distributions of Rhodiola species appear to be shaped by temperature-related
      variables. The southeastern QTP, and especially the Hengduan Mountains, were the
      origin and center of distribution for Rhodiola, and also served as refugia during
      the LGM. Under future climate scenario in 2050, Rhodiola species might have to
      migrate upward and northward, but many species would expand their ranges contra
      the prediction of the "nowhere to go" hypothesis, caused by the appearance of
      additional potential habitat concomitant with the reduction of permafrost with
      climate warming.

PMID- 29651148
TI  - Author Correction: Potential impacts of climate change on habitat suitability for
      the Queensland fruit fly.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 29651149
TI  - Author Correction: CRISPR/Cas9-derived models of ovarian high grade serous
      carcinoma targeting Brca1, Pten and Nf1, and correlation with platinum
      sensitivity.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 29651150
TI  - Energy-loss return gate via liquid dielectric polarization.
AB  - There has been much research on renewable energy-harvesting techniques. However,
      owing to increasing energy demands, significant energy-related issues remain to
      be solved. Efforts aimed at reducing the amount of energy loss in
      electric/electronic systems are essential for reducing energy consumption and
      protecting the environment. Here, we design an energy-loss return gate system
      that reduces energy loss from electric/electronic systems by utilizing the
      polarization of liquid dielectrics. The use of a liquid dielectric material in
      the energy-loss return gate generates electrostatic potential energy while
      reducing the dielectric loss of the electric/electronic system. Hence, an energy
      loss return gate can make breakthrough impacts possible by amplifying energy
      harvesting efficiency, lowering the power consumption of electronics, and storing
      the returned energy. Our study indicates the potential for enhancing energy
      harvesting technologies for electric/electronics systems, while increasing the
      widespread development of these systems.

PMID- 29651151
TI  - The effect of ageing and osteoarthritis on the mechanical properties of cartilage
      and bone in the human knee joint.
AB  - Osteoarthritis is traditionally associated with cartilage degeneration although
      is now widely accepted as a whole-joint disease affecting the entire
      osteochondral unit; however site-specific cartilage and bone material properties
      during healthy ageing and disease are absent limiting our understanding.
      Cadaveric specimens (n = 12; 31-88 years) with grades 0-4 osteoarthritis, were
      dissected and spatially correlated cartilage, subchondral and trabecular bone
      samples (n = 8 per cadaver) were harvested from femoral and tibial localities.
      Nanoindentation was utilised to obtain cartilage shear modulus (G') and bone
      elastic modulus (E). Cartilage G' is strongly correlated to age (p = 0.003) and
      osteoarthritis grade (p = 0.007). Subchondral bone E is moderately correlated to
      age (p = 0.072) and strongly correlated to osteoarthritis grade (p = 0.013).
      Trabecular bone E showed no correlation to age (p = 0.372) or osteoarthritis
      grade (p = 0.778). Changes to cartilage G' was significantly correlated to
      changes in subchondral bone E (p = 0.007). Results showed preferential medial
      osteoarthritis development and moderate correlations between cartilage G' and
      sample location (p = 0.083). Also demonstrated for the first time was significant
      correlations between site-matched cartilage and subchondral bone material
      property changes during progressive ageing and osteoarthritis, supporting the
      role of bone in disease initiation and progression. This clinically relevant data
      indicates a causative link with osteoarthritis and medial habitual loading.

PMID- 29651152
TI  - Novel crab predator causes marine ecosystem regime shift.
AB  - The escalating spread of invasive species increases the risk of disrupting the
      pathways of energy flow through native ecosystems, modify the relative importance
      of resource ('bottom-up') and consumer ('top-down') control in food webs and
      thereby govern biomass production at different trophic levels. The current lack
      of understanding of interaction cascades triggered by non-indigenous species
      underscores the need for more basic exploratory research to assess the degree to
      which novel species regulate bottom-up and/or top down control. Novel predators
      are expected to produce the strongest effects by decimating consumers, and
      leading to the blooms of primary producers. Here we show how the arrival of the
      invasive crab Rhithropanopeus harrisii into the Baltic Sea - a bottom-up
      controlled ecosystem where no equivalent predators ever existed - appeared to
      trigger not only strong top-down control resulting in a decline in richness and
      biomass of benthic invertebrates, but also an increase in pelagic nutrients and
      phytoplankton biomass. Thus, the addition of a novel interaction - crab predation
      - to an ecosystem has a potential to reduce the relative importance of bottom-up
      regulation, relax benthic-pelagic coupling and reallocate large amounts of
      nutrients from benthic to pelagic processes, resulting in a regime shift to a
      degraded ecosystem state.

PMID- 29651153
TI  - Decipher reliable biomarkers of brain aging by integrating literature-based
      evidence with interactome data.
AB  - Aging is an inevitable progressive decline in every physiological function and
      serves as a primary risk factor for cognitive decline and Alzheimer's disease.
      Thus, age-dependent impairments in cognitive function must be understood in
      association with general aging processes with an integrative approach in a
      systemic manner. An integrative aging gene network was constructed based on
      mutual molecular interactions using literature-curated interactome data and
      separated into functionally distinct modules. To investigate key surrogate
      biomarkers of the aging brain in the context of the general aging process, co
      expression networks were built on post-mortem and Alzheimer's brain transcriptome
      data. In both the normal aging brain and the brain affected by Alzheimer's
      disease, the immune-related co-expression module was positively correlated with
      advancing age, whereas the synaptic transmission-related co-expression module was
      decreased with age. Importantly, the network topology-based analysis indicated
      that complement system genes were prioritized as a surrogate biomarker in
      evaluating the process of brain aging. Our public data-centered analysis coupled
      with experimental validation revealed that the complement system is likely to be
      a master regulator in initiating and regulating the immune system in the aging
      brain and could serve as reliable and surrogate biomarkers for the diagnosis of
      cognitive dysfunction.

PMID- 29651154
TI  - Effect of Concentrated Growth Factor (CGF) on the Promotion of Osteogenesis in
      Bone Marrow Stromal Cells (BMSC) in vivo.
AB  - The therapeutic method traditionally used in bone defect reconstruction is
      autologous bone grafting. The most common problems affecting this type of repair
      approach are bone absorption and donor trauma. The approach taken in this study
      overcomes these problems. Bone marrow stromal cells (BMSCs) provided the crucial
      seed cells. Fibrin biological scaffolds were formed by combining the BMSCs with
      concentrated growth factor (CGF). BMSCs were isolated from Wistar rat femurs; CGF
      was prepared from rat heart blood. Five repair groups were created for
      comparative purposes: (A) CGF + BMSCs; (B) CGF; (C) collagen + BMSCs; (D)
      collagen; (E) blank. After three months, the rats were sacrificed, and
      histopathology and three-dimensional CT images produced. Bone regeneration was
      significantly higher in the (A) CGF + BMSC group; osteogenesis was lower in the
      (B) CGF and (C) collagen + BMSC groups, at very similar levels; the (D) collagen
      and (E) blank groups scored the lowest results. Our research suggests that
      combining CGF with BMSCs leads to the formation of fibrin scaffolds that have a
      powerful effect on osteogenesis as well as a subsidiary angiogenic effect. SEM
      images of the CGF scaffolds cultured with BMSCs confirmed good CGF
      biocompatibility. The superior osteoinductive activity of the CGF + BMSC
      combination makes it an excellent biomaterial for bone regeneration.

PMID- 29651155
TI  - Epigenetic activation during T helper 17 cell differentiation is mediated by
      Tripartite motif containing 28.
AB  - Epigenetic regulation is important for T-cell fate decision. Although STAT3 is
      known to initiate Th17 differentiation program, the downstream mechanism is
      unclear. Here we show that Tripartite motif containing 28 (Trim28) expression in
      Th17 cells is required for Th17-mediated cytokine production and experimental
      autoimmune diseases. Genome-wide occupancy analysis reveals that TRIM28-bound
      regions overlap with almost all Th17-specific super-enhancers (SE), and that
      those SEs are impaired by the deficiency of STAT3 or TRIM28, but not of
      RORgammat. Importantly, IL-6-STAT3 signaling facilitates TRIM28 binding to the
      Il17-Il17f locus, and this process is required for epigenetic activation and high
      order chromosomal interaction. TRIM28 also forms a complex with STAT3 and
      RORgammat, and promotes the recruitment of RORgammat to its target cytokine
      genes. Our study thus suggests TRIM28 to be important for the epigenetic
      activation during Th17 cell differentiation, and prompts the potential use of
      epigenetic interventions for Th17-related autoimmune diseases.

PMID- 29651156
TI  - Efficient differentiation of cardiomyocytes and generation of calcium-sensor
      reporter lines from nonhuman primate iPSCs.
AB  - Nonhuman primate (NHP) models are more predictive than rodent models for
      developing induced pluripotent stem cell (iPSC)-based cell therapy, but robust
      and reproducible NHP iPSC-cardiomyocyte differentiation protocols are lacking for
      cardiomyopathies research. We developed a method to differentiate integration
      free rhesus macaque iPSCs (RhiPSCs) into cardiomyocytes with >85% purity in 10
      days, using fully chemically defined conditions. To enable visualization of
      intracellular calcium flux in beating cardiomyocytes, we used CRISPR/Cas9 to
      stably knock-in genetically encoded calcium indicators at the rhesus AAVS1 safe
      harbor locus. Rhesus cardiomyocytes derived by our stepwise differentiation
      method express signature cardiac markers and show normal electrochemical
      coupling. They are responsive to cardiorelevant drugs and can be successfully
      engrafted in a mouse myocardial infarction model. Our approach provides a
      powerful tool for generation of NHP iPSC-derived cardiomyocytes amenable to
      utilization in basic research and preclinical studies, including in vivo tissue
      regeneration models and drug screening.

PMID- 29651157
TI  - Bilayer synergetic coupling double negative acoustic metasurface and cloak.
AB  - In this paper, we propose a bilayer plate-type lightweight double negative
      metasurface based on a new synergetic coupling design concept, by which the
      perfect absorption, double negative bands, free manipulation of phase shifts with
      a 2pi span and acoustic cloak can be successively realized. Firstly, the
      synergetic behavior between resonant and anti-resonant plates is presented to
      construct a bilayer unit in which each component respectively provides a pre
      defined function in realizing the perfect absorption. Based on this bilayer
      structure, a double negative band with simultaneously negative effective mass
      density and bulk modulus is obtained, which, as a metasurface, can obtain
      continuous phase shifts almost completely covering a 2pi range, thus facilitating
      the design of a three-dimensional (3D) acoustic cloak. In addition, based on this
      strong sound absorption concept, a two-dimensional (2D) omnidirectional broadband
      acoustical dark skin, covering between 800 to 6000 Hz, is also demonstrated
      through the proposed bilayer plate-type structure form. The proposed design
      concepts and metasurfaces have widespread potential application values in strong
      sound attenuation, filtering, superlens, imaging, cloak, and extraordinary wave
      steering, in which the attributes of strong absorption, double negative
      parameters or continuous phase shifts with full 2pi span are required to realize
      the expected extraordinary physical features.

PMID- 29651158
TI  - Effect of dietary probiotics on the semen traits and antioxidative activity of
      male broiler breeders.
AB  - This study aimed to investigate the effect of probiotics on the intestinal
      morphology, intestinal microflora, oxidative activity (biological antioxidant
      potential), and semen quality of male broiler breeders. For this, 180 Cobb male
      broiler breeders (60 weeks of age) were randomly distributed into two groups. The
      control group was fed a basal diet, and the probiotics group was fed basal diet
      supplemented with probiotics for 6 weeks. Probiotics containing Bacillus
      amyloliquefaciens TOA5001 improved the above mentioned characteristics of the
      male broiler breeders. Thus, B. amyloliquefaciens TOA5001 might improve the
      reproductive performance of male broiler breeders.

PMID- 29651159
TI  - Publisher Correction: Selective Tropism of Dengue Virus for Human Glycoprotein
      Ib.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 29651161
TI  - Publisher Correction: Shedding light on the neonatal brain: probing cerebral
      hemodynamics by diffuse optical spectroscopic methods.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 29651160
TI  - Structure and co-occurrence patterns in microbial communities under acute
      environmental stress reveal ecological factors fostering resilience.
AB  - Understanding the factors that modulate bacterial community assembly in natural
      soils is a longstanding challenge in microbial community ecology. In this work,
      we compared two microbial co-occurrence networks representing bacterial soil
      communities from two different sections of a pH, temperature and humidity
      gradient occurring along a western slope of the Andes in the Atacama Desert. In
      doing so, a topological graph alignment of co-occurrence networks was used to
      determine the impact of a shift in environmental variables on OTUs taxonomic
      composition and their relationships. We observed that a fraction of association
      patterns identified in the co-occurrence networks are persistent despite large
      environmental variation. This apparent resilience seems to be due to: (1) a
      proportion of OTUs that persist across the gradient and maintain similar
      association patterns within the community and (2) bacterial community ecological
      rearrangements, where an important fraction of the OTUs come to fill the
      ecological roles of other OTUs in the other network. Actually, potential
      functional features suggest a fundamental role of persistent OTUs along the soil
      gradient involving nitrogen fixation. Our results allow identifying factors that
      induce changes in microbial assemblage configuration, altering specific bacterial
      soil functions and interactions within the microbial communities in natural
      environments.

PMID- 29651162
TI  - Quantitative Methods to Monitor RNA Biomarkers in Myotonic Dystrophy.
AB  - Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are human neuromuscular
      disorders associated with mutations of simple repetitive sequences in affected
      genes. The abnormal expansion of CTG repeats in the 3'-UTR of the DMPK gene
      elicits DM1, whereas elongated CCTG repeats in intron 1 of ZNF9/CNBP triggers
      DM2. Pathogenesis of both disorders is manifested by nuclear retention of
      expanded repeat-containing RNAs and aberrant alternative splicing. The precise
      determination of absolute numbers of mutant RNA molecules is important for a
      better understanding of disease complexity and for accurate evaluation of the
      efficacy of therapeutic drugs. We present two quantitative methods, Multiplex
      Ligation-Dependent Probe Amplification and droplet digital PCR, for studying the
      mutant DMPK transcript (DMPKexpRNA) and the aberrant alternative splicing in DM1
      and DM2 human tissues and cells. We demonstrate that in DM1, the DMPKexpRNA is
      detected in higher copy number than its normal counterpart. Moreover, the
      absolute number of the mutant transcript indicates its low abundance with only a
      few copies per cell in DM1 fibroblasts. Most importantly, in conjunction with
      fluorescence in-situ hybridization experiments, our results suggest that in DM1
      fibroblasts, the vast majority of nuclear RNA foci consist of a few molecules of
      DMPKexpRNA.

PMID- 29651163
TI  - Prospective Comparison of QFT-GIT and T-SPOT.TB Assays for Diagnosis of Active
      Tuberculosis.
AB  - T-SPOT.TB and QuantiFERON-TB Gold In-Tube (QFT-GIT) tests, as two commercial
      blood assays for diagnosing active tuberculosis (ATB), are not yet fully
      validated. Especially, there are no reports on comparing the efficacy between the
      two tests in the same population in China. A multicenter, prospective comparison
      study was undertaken at four hospitals specializing in pulmonary diseases. A
      total of 746 suspected pulmonary TB were enrolled and categorized, including 185
      confirmed TB, 298 probable TB and 263 non-TB. Of 32 patients with indeterminate
      test results (ITRs), age and underlying disease were associated with the rate of
      ITRs. Furthermore, the rate of ITRs determined by T-SPOT.TB was lower than QFT
      GIT (0.4% vs. 4.3%, P < 0.01). When excluding ITRs, the sensitivities of T
      SPOT.TB and QFT-GIT were 85.2% and 84.8%, and specificities of 63.4% and 60.5%,
      respectively in the diagnosis of ATB. The two assays have an overall agreement of
      92.3%, but exhibited a poor linear correlation (r2 = 0.086) between the levels of
      interferon-gamma release detected by the different assays. Although having some
      heterogeneity in detecting interferon-gamma release, both the QFT-GIT and T
      SPOT.TB demonstrated high concordance in diagnosing ATB. However, neither of them
      showed suitability in the definitive diagnosis of the disease.

PMID- 29651164
TI  - Genome wide analysis of the transition to pathogenic lifestyles in Magnaporthales
      fungi.
AB  - The rice blast fungus Pyricularia oryzae (syn. Magnaporthe oryzae, Magnaporthe
      grisea), a member of the order Magnaporthales in the class Sordariomycetes, is an
      important plant pathogen and a model species for studying pathogen infection and
      plant-fungal interaction. In this study, we generated genome sequence data from
      five additional Magnaporthales fungi including non-pathogenic species, and
      performed comparative genome analysis of a total of 13 fungal species in the
      class Sordariomycetes to understand the evolutionary history of the
      Magnaporthales and of fungal pathogenesis. Our results suggest that the
      Magnaporthales diverged ca. 31 millon years ago from other Sordariomycetes, with
      the phytopathogenic blast clade diverging ca. 21 million years ago. Little
      evidence of inter-phylum horizontal gene transfer (HGT) was detected in
      Magnaporthales. In contrast, many genes underwent positive selection in this
      order and the majority of these sequences are clade-specific. The blast clade
      genomes contain more secretome and avirulence effector genes, which likely play
      key roles in the interaction between Pyricularia species and their plant hosts.
      Finally, analysis of transposable elements (TE) showed differing proportions of
      TE classes among Magnaporthales genomes, suggesting that species-specific
      patterns may hold clues to the history of host/environmental adaptation in these
      fungi.

PMID- 29651166
TI  - Energy expenditure for massage therapists during performing selected classical
      massage techniques.
AB  - OBJECTIVES: The aim of the study is to evaluate the intensity of the effort and
      energy expenditure in the course of performing selected classical massage
      techniques and to assess the workload of a massage therapist during a work shift.
      MATERIAL AND METHODS: Thirteen massage therapists (age: 21.9+/-1.9 years old,
      body mass index: 24.5+/-2.8 kg*m<sup>-2</sup>, maximal oxygen consumption * body
      mass<sup>-1</sup> (VO<sub>2max</sub>*BM<sup>-1</sup>): 42.3+/-7 ml*kg<sup>
      1</sup>*min<sup>-1</sup>) were involved in the study. The stress test consisted
      in performing selected classical massage techniques in the following order:
      stroking, kneading, shaking, beating, rubbing and direct vibration, during which
      the cardio-respiratory responses and the subjective rating of perceived exertion
      (RPE) were assessed. Intensity of exercise during each massage technique was
      expressed as % VO<sub>2max</sub>, % maximal heart rate (HR<sub>max</sub>) and %
      heart rate reserve (HRR). During each massage technique, net energy expenditure
      (EE) and energy cost of work using metabolic equivalent of task (MET) were
      determined. RESULTS: The intensity of exercise was 47.2+/-6.2% as expressed in
      terms of % VO<sub>2max</sub>, and 74.7+/-3.2% as expressed in terms of %
      HR<sub>max</sub>, while it was 47.8+/-1.7% on average when expressed in terms of
      % HRR during the whole procedure. While performing the classical massage, the
      average EE and MET were 5.6+/-0.9 kcal*min<sup>-1</sup> and 5.6+/-0.2,
      respectively. The average RPE calculated for the entire procedure was 12.1+/-1.4.
      During the performance of a classical massage technique for a single treatment
      during the study, the average total EE was 176.5+/-29.6 kcal, resulting in an
      energy expenditure of 336.2+/-56.4 kcal*h<sup>-1</sup>. In the case of the
      classical massage technique, rubbing was the highest intensity exercise for the
      masseur who performed the massage (%VO<sub>2max</sub> = 57.4+/-13.1%,
      HR<sub>max</sub> = 79.6+/-7.7%, HRR = 58.5+/-13.1%, MET = 6.7+/-1.1, EE = 7.1+/
      1.4 kcal*min<sup>-1</sup>, RPE = 13.4+/-1.3). CONCLUSIONS: In the objective
      assessment, physical exercise while performing a single classical massage is
      characterized by hard work. The technique of classical massage during which the
      masseur performs the highest exercise intensity is rubbing. According to the
      classification of work intensity based on energy expenditure, the masseur's work
      is considered heavy during the whole work shift. Int J Occup Med Environ Health
      2018;31(5):677-684.

PMID- 29651167
TI  - CONSTRAINING RELATIVISTIC BOW SHOCK PROPERTIES IN ROTATION-POWERED MILLISECOND
      PULSAR BINARIES.
AB  - Multiwavelength followup of unidentified Fermi sources has vastly expanded the
      number of known galactic-field "black widow" and "redback" millisecond pulsar
      binaries. Focusing on their rotation-powered state, we interpret the radio to X
      ray phenomenology in a consistent framework. We advocate the existence of two
      distinct modes differing in their intrabinary shock orientation, distinguished by
      the phase-centering of the double-peaked X-ray orbital modulation originating
      from mildly-relativistic Doppler boosting. By constructing a geometric model for
      radio eclipses, we constrain the shock geometry as functions of binary
      inclination and shock stand-off R0. We develop synthetic X-ray synchrotron
      orbital light curves and explore the model parameter space allowed by radio
      eclipse constraints applied on archetypal systems B1957+20 and J1023+0038. For
      B1957+20, from radio eclipses the stand-off is R0 ~ 0.15-0.3 fraction of binary
      separation from the companion center, depending on the orbit inclination.
      Constructed X-ray light curves for B1957+20 using these values are qualitatively
      consistent with those observed, and we find occultation of the shock by the
      companion as a minor influence, demanding significant Doppler factors to yield
      double peaks. For J1023+0038, radio eclipses imply R0 ? 0.4 while X-ray light
      curves suggest 0.1 ? R0 ? 0.3 (from the pulsar). Degeneracies in the model
      parameter space encourage further development to include transport
      considerations. Generically, the spatial variation along the shock of the
      underlying electron power-law index should yield energy-dependence in the shape
      of light curves motivating future X-ray phase-resolved spectroscopic studies to
      probe the unknown physics of pulsar winds and relativistic shock acceleration
      therein.

PMID- 29651165
TI  - The mitochondrial citrate carrier, SLC25A1, drives stemness and therapy
      resistance in non-small cell lung cancer.
AB  - Therapy resistance represents a clinical challenge for advanced non-small cell
      lung cancer (NSCLC), which still remains an incurable disease. There is growing
      evidence that cancer-initiating or cancer stem cells (CSCs) provide a reservoir
      of slow-growing dormant populations of cells with tumor-initiating and unlimited
      self-renewal ability that are left behind by conventional therapies reigniting
      post-therapy relapse and metastatic dissemination. The metabolic pathways
      required for the expansion of CSCs are incompletely defined, but their
      understanding will likely open new therapeutic opportunities. We show here that
      lung CSCs rely upon oxidative phosphorylation for energy production and survival
      through the activity of the mitochondrial citrate transporter, SLC25A1. We
      demonstrate that SLC25A1 plays a key role in maintaining the mitochondrial pool
      of citrate and redox balance in CSCs, whereas its inhibition leads to reactive
      oxygen species build-up thereby inhibiting the self-renewal capability of CSCs.
      Moreover, in different patient-derived tumors, resistance to cisplatin or to
      epidermal growth factor receptor (EGFR) inhibitor treatment is acquired through
      SLC25A1-mediated implementation of mitochondrial activity and induction of a
      stemness phenotype. Hence, a newly identified specific SLC25A1 inhibitor is
      synthetic lethal with cisplatin or with EGFR inhibitor co-treatment and restores
      antitumor responses to these agents in vitro and in animal models. These data
      have potential clinical implications in that they unravel a metabolic
      vulnerability of drug-resistant lung CSCs, identify a novel SLC25A1 inhibitor
      and, lastly, provide the first line of evidence that drugs, which block SLC25A1
      activity, when employed in combination with selected conventional antitumor
      agents, lead to a therapeutic benefit.

PMID- 29651168
TI  - LOCUS OF CONTROL AND ITS INTERGENERATIONAL IMPLICATIONS FOR EARLY CHILDHOOD SKILL
      FORMATION.
AB  - This article builds upon Cunha's (2015) subjective rationality model in which
      parents have a subjective belief about the impact of their investment on their
      children's early skill formation. We propose that this subjective belief is
      determined partly by locus of control (LOC), i.e. the extent to which individuals
      believe that their actions can influence future outcomes. Consistent with the
      theory, we show that maternal LOC measured at the 12th week of gestation strongly
      predicts maternal attitudes towards parenting style and actual time investments.
      We also utilise maternal LOC to improve the specification typically used to
      estimate skill production function parameters.

PMID- 29651169
TI  - Persistence of Bowl Water Contamination during Sequential Flushes of Contaminated
      Toilets.
AB  - Toilets contaminated with infectious organisms are a recognized contact disease
      transmission hazard. Previous studies indicate that toilet bowl water can remain
      contaminated for several flushes after the contamination occurs. This study
      characterized contamination persistence over an extended series of flushes using
      both indicator particles and viable bacteria. For this study, toilets were seeded
      with microbe-size microbial surrogates and with Pseudomonas fluorescens or
      Clostridium difficile bacteria and flushed up to 24 times. Bowl water samples
      collected after seeding and after each flush indicated the clearance per flush
      and residual bowl water contaminant concentration. Toilets exhibited 3 + log10
      contaminant reductions with the first flush, only 1-2 logs with the second flush,
      and less than 1 log thereafter. Contamination still was present 24 flushes post
      contamination. Clearance was modeled accurately by a two-stage exponential decay
      process. This study shows that toilet bowl water will remain contaminated many
      flushes after initial contamination, posing a risk of recurring environmental
      contamination and associated infection incidence.

PMID- 29651170
TI  - On the secondary eyewall formation of Hurricane Edouard (2014).
AB  - A first observationally-based estimation of departures from gradient wind balance
      during secondary eyewall formation is presented. The study is based on the
      Atlantic Hurricane Edouard (2014). This storm was observed during the National
      Aeronautics and Space Administration's (NASA) Hurricane and Severe Storm Sentinel
      (HS3) experiment, a field campaign conducted in collaboration with the National
      Oceanic and Atmospheric Administration (NOAA). A total of 135 dropsondes are
      analyzed in two separate time periods: one named the secondary eyewall formation
      period and the other one referred to as the decaying-double eyewalled storm
      period. During the secondary eyewall formation period, a time when the storm was
      observed to have only one eyewall, the diagnosed agradient force has a secondary
      maxima that coincides with the radial location of the secondary eyewall observed
      in the second period of study. The maximum spin up tendency of the radial influx
      of absolute vertical vorticity is within the boundary layer in the region of the
      eyewall of the storm and the spin up tendency structure elongates radially
      outward into the secondary region of supergradient wind, where the secondary wind
      maxima is observed in the second period of study. An analysis of the boundary
      layer averaged vertical structure of equivalent potential temperature reveals a
      conditionally unstable environment in the secondary eyewall formation region.
      These findings support the hypothesis that deep convective activity in this
      region contributed to spin up of the boundary layer tangential winds and the
      formation of a secondary eyewall that is observed during the decaying-double
      eyewalled storm period.

PMID- 29651171
TI  - Wastewater: A Potential Bioenergy Resource.
AB  - Wastewaters are a rich source of nutrients for microorganisms. However, if left
      unattended the biodegradation may lead to severe environmental hazards. The
      wastewaters can thus be utilized for the production of various value added
      products including bioenergy (H2 and CH4). A number of studies have reported
      utilization of various wastewaters for energy production. Depending on the nature
      of the wastewater, different reactor configurations, wastewater and inoculum
      pretreatments, co-substrate utilizations along with other process parameters have
      been studied for efficient product formation. Only a few studies have reported
      sequential utilization of wastewaters for H2 and CH4 production despite its huge
      potential for complete waste degradation.

PMID- 29651172
TI  - Virulence Factors in Candida albicans and Streptococcus mutans Biofilms Mediated
      by Farnesol.
AB  - The aim of this study was to evaluate the effect of farnesol on the production of
      acids and hydrolytic enzymes by biofilms of Streptococcus mutans and Candida
      albicans. The present study also evaluated the time-kill curve and the effect of
      farnesol on matrix composition and structure of single-species and dual-species
      biofilms. Farnesol, at subinhibitory concentrations, showed a significant
      reduction in S. mutans biofilm acid production, but did not alter C. albicans
      hydrolytic enzyme production. The number of cultivable cells of both
      microorganisms was significantly reduced after 8 h of contact with farnesol.
      Extracellular matrix protein content was reduced for biofilms formed in the
      presence of farnesol. In addition, confocal laser scanning and scanning electron
      microscopy displayed structural alterations in all biofilms treated with
      farnesol, which included reduction in viable cells and extracellular matrix. In
      conclusion, farnesol showed favorable properties controlling some virulence
      factors of S. mutans and C. albicans biofilms. These findings should stimulate
      further studies using this quorum-sensing molecule, combined with other drugs, to
      prevent or treat biofilm-associated oral diseases.

PMID- 29651173
TI  - In Vitro Anticancer Activity of Staphyloxanthin Pigment Extracted from
      Staphylococcus gallinarum KX912244, a Gut Microbe of Bombyx mori.
AB  - The present study reports the in vitro biological nature of the pigment produced
      by Staphylococcus gallinarum KX912244, isolated as the gut microflora bacterium
      of the insect Bombyx mori. The purified pigment was characterized as
      Staphyloxanthin based on bio-physical characterization techniques like Fourier
      transform infrared spectroscopy, high performance liquid chromatography, Proton
      nuclear magnetic resonance spectroscopy (1H NMR), Liquid chromatography-Mass
      spectroscopy and Gas chromatography-Mass spectroscopy. The Staphyloxanthin
      pigment presented considerable biological properties including in vitro
      antimicrobial activity against pathogens Staphylococcus aureus, Escherichia coli
      and Candida albicans; in vitro antioxidant activity by % DPPH free radical
      scavenging activity showing IC50 value of 54.22 ug/mL; DNA damage protection
      activity against reactive oxygen species and anticancer activity evaluated by
      cytotoxicity assay against 4 different cancer cell lines like the Dalton's
      lymphoma ascites with IC50 value 6.20 +/- 0.02 ug/mL, Ehrlich ascites carcinoma
      having IC50 value 6.48 +/- 0.15 ug/mL, Adenocarcinomic human alveolar basal
      epithelial cells (A549 Lung carcinoma) bearing IC50 value 7.23 +/- 0.11 ug/mL and
      Mus mucus skin melanoma (B16F10) showing IC50 value 6.58 +/- 0.38 ug/mL and less
      cytotoxicity towards non-cancerous human fibroblast cell lines (NIH3T3) with IC50
      value of 52.24 ug/mL. The present study results suggest that Staphyloxanthin acts
      as a potential therapeutic agent especially due to its anticancer property.

PMID- 29651174
TI  - Identification and Pathogenicity of Fungal Pathogens Causing Black Point in Wheat
      on the North China Plain.
AB  - Fungi associated with black point were isolated from three highly susceptible
      wheat genotypes in the North China Plain. The 21 isolates represented 11 fungal
      genera. The most prevalent genera were Alternaria (isolation frequency of 56.7%),
      Bipolaris (16.1%), and Fusarium (6.0%). The other eight genera were Curvularia,
      Aspergillus, Cladosporium, Exserohilum, Epicoccum, Nigrospora, Penicillium, and
      Ulocladium; their isolation frequencies ranged from 0.8 to 4.8%. The
      pathogenicity of the isolates was individually assessed in the greenhouse by
      inoculating wheat plants with spore suspensions. Ten of the 21 isolates caused
      significantly higher incidences of black point than that the controls. These
      isolates belonged to eight fungal species (A. alternata, B. sorokiniana, B.
      crotonis, B. cynodontis, C. spicifera, F. equiseti, E. rostratum, and E.
      sorghinum) based on morphological traits and phylogenetic analysis. The average
      incidences of black point in the eight fungal species were 32.4, 54.3, 43.0,
      41.9, 37.2, 38.8, 50.1, and 34.1%, respectively. B. sorokiniana and A. alternata
      were determined to be the most important pathogens in the North China Plain based
      on fungal prevalence and symptom severity. This study is the first to identify E.
      rostratum as a major pathogen causing black point in wheat.

PMID- 29651175
TI  - Adaptive Strategies of Bacillus thuringiensis Isolated from Acid Mine Drainage
      Site in Sabah, Malaysia.
AB  - The adaptive process in bacteria is driven by specific genetic elements which
      regulate phenotypic characteristics such as tolerance to high metal ion
      concentrations and the secretion of protective biofilms. Extreme environments
      such as those associated with heavy metal pollution and extremes of acidity offer
      opportunities to study the adaptive mechanisms of microorganisms. This study
      focused on the genome analysis of Bacillus thuringiensis (Bt MCMY1), a gram
      positive rod shaped bacterium isolated from an acid mine drainage site in Sabah,
      Malaysia by using a combination of Single Molecule Real Time DNA Sequencing,
      Scanning Electron Microscopy (SEM) and Fourier Transform Infrared Spectroscopy
      (FTIR). The genome size of Bt MCMY1 was determined to be 5,458,152 bases which
      was encoded on a single chromosome. Analysis of the genome revealed genes
      associated with resistance to Copper, Mercury, Arsenic, Cobalt, Zinc, Cadmium and
      Aluminum. Evidence from SEM and FTIR indicated that the bacterial colonies form
      distinct films which bear the signature of polyhydroxyalkanoates (PHA) and this
      finding was supported by the genome data indicating the presence of a genetic
      pathway associated with the biosynthesis of PHAs. This is the first report of a
      Bacillus sp. isolated from an acid mine drainage site in Sabah, Malaysia and the
      genome sequence will provide insights into the manner in which B. thuringiensis
      adapts to acid mine drainage.

PMID- 29651176
TI  - Cloning of ompA gene from Acinetobacter baumannii into the eukaryotic expression
      vector pBudCE4.1 as DNA vaccine.
AB  - Antibiotic resistant features of Acinetobacter baumannii is partly due to the
      decreased outer membrane proteins (OMPs) permeability. The OmpA is one of the
      most conserved proteins among A. baumannii with a considerable antigenic
      potential to stimulate the multidimensional immune system responses. The present
      study was aimed to clone the ompA gene into the eukaryotic expression vector with
      potential as DNA vaccine. The ompA gene of A. baumannii was amplified using
      polymerase chain reaction (PCR). The target DNA was cloned and sub-cloned into
      the pTZ57R/T and pBudCE4.1 vectors, respectively. The recombinant vectors
      containing ompA were then validated using colony PCR, vector sequencing and
      double-digestion strategies. The pBudCE4.1-ompA recombinant plasmid was
      transfected into the human dermal fibroblast cells (HDF) and presence of ompA
      transcript and protein was evaluated using reverse transcribed-PCR (RT-PCR) and
      sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Our finding
      from colony PCR, sequencing and enzyme double digestion result confirmed that
      target gene has been successfully inserted into the pTZ57RT and pBudCE4.1. The
      presence of an expected band (1112 bp) in RT-PCR as wells as a ~ 38 kDa band
      during SDS-PAGE showed that the recombinant pBudCE4.1-ompA construct was
      efficiently transfected into the HDF cells and expressed. Altogether, our
      observation demonstrated that the recombinant pBudCE4.1-ompA construct was
      successfully produced although further experiments are needed.

PMID- 29651177
TI  - Potential of Marine-Derived Fungi to Remove Hexavalent Chromium Pollutant from
      Culture Broth.
AB  - Chromium (Cr) released from industrial units such as tanneries, textile and
      electroplating industries is detrimental to the surrounding ecosystems and human
      health. The focus of the present study was to check the Cr(VI) removal efficiency
      by marine-derived fungi from liquid broth. Amongst the three Cr(VI) tolerant
      isolates, #NIOSN-SK56-S19 (Aspergillus sydowii) showed Cr-removal efficiency of
      0.01 mg Cr mg-1 biomass resulting in 26% abatement of total Cr with just 2.8 mg
      of biomass produced during the growth in 300 ppm Cr(VI). Scanning Electron
      Microscopy revealed aggregation of mycelial biomass with exopolysaccharide, while
      Electron Dispersive Spectroscopy showed the presence of Cr2O3 inside the biomass
      indicating presence of active Cr(VI) removal mechanisms. This was further
      supported when the Cr(VI) removal was monitored using DPC (1,5-diphenylcarbazide)
      method. The results of this study point to the potential of marine-derived fungal
      isolates for Cr(VI) removal.

PMID- 29651178
TI  - Transformation Products of Carbamazepine (CBZ) After Ozonation and their Toxicity
      Evaluation Using Pseudomonas sp. Strain KSH-1 in Aqueous Matrices.
AB  - Carbamazepine (CBZ) is an anti-epileptic and anti-convulsant drug widely used for
      the treatment of epilepsy and other bipolar disorders. Ozone as an advanced
      oxidation process has been widely used for the degradation of CBZ resulting in
      the formation of transformation products (ozonides). The present research aims to
      isolate and identify potential microorganism, capable of degradation of CBZ and
      its transformation products. The cell viability and cytotoxicity of pure CBZ and
      their ozone transformation products were evaluated using the cells of Pseudomonas
      sp. strain KSH-1 through cell viability assay tests. The cells metabolic activity
      was assessed at varying CBZ concentrations (~ 10-25 ppm, pure CBZ) and
      cumulatively for ozone transformation products. For pure CBZ, % cell viability
      decreases as CBZ concentration increases, while, in case of post-ozonated CBZ
      transformation products, the viability decreases initially and then increases
      upon exposure of ozone with a maximum cell viability of 97 +/- 2.8% evaluated for
      2 h post-ozonated samples.

PMID- 29651179
TI  - Incubation of Aquilaria subintegra with Microbial Culture Supernatants Enhances
      Production of Volatile Compounds and Improves Quality of Agarwood Oil.
AB  - Incubation with microbial culture supernatants improved essential oil yield from
      Aquilaria subintegra woodchips. The harvested woodchips were incubated with de
      man, rogosa and sharpe (MRS) agar, yeast mold (YM) agar medium and six different
      microbial culture supernatants obtained from Lactobacillus bulgaricus, L.
      acidophilus, Streptococcus thermophilus, Lactococcus lactis, Saccharomyces
      carlsbergensis and S. cerevisiae prior to hydrodistillation. Incubation with
      lactic acid bacteria supernatants provided higher yield of agarwood oil (0.45%
      w/w) than that obtained from yeast (0.25% w/w), agar media (0.23% w/w) and water
      (0.22% w/w). The composition of agarwood oil from all media and microbial
      supernatant incubations was investigated by using gas chromatography-mass
      spectrometry. Overall, three major volatile profiles were obtained, which
      corresponded to water soaking (control), as well as, both YM and MRS media,
      lactic acid bacteria, and yeast supernatant incubations. Sesquiterpenes and their
      oxygenated derivatives were key components of agarwood oil. Fifty-two volatile
      components were tentatively identified in all samples. Beta-agarofuran, alpha
      eudesmol, karanone, alpha-agarofuran and agarospirol were major components
      present in most of the incubated samples, while S. cerevisiae-incubated A.
      subintegra provided higher amount of phenyl acetaldehyde. Microbial culture
      supernatant incubation numerically provided the highest yield of agarwood oil
      compared to water soaking traditional method, possibly resulting from activity of
      extracellular enzymes produced by the microbes. Incubation of agarwood with
      lactic acid bacteria supernatant significantly enhanced oil yields without
      changing volatile profile/composition of agarwood essential oil, thus this is a
      promising method for future use.

PMID- 29651180
TI  - Production of a Mixture of Fengycins with Surfactant and Antifungal Activities by
      Bacillus sp. MA04, a Versatile PGPR.
AB  - Bacillus sp. strain MA04 a plant growth-promoting rhizobacteria (PGPR) showed
      hemolytic activity on blood agar plates, and the supernatant from liquid culture
      in nutrient broth at 24 h exhibited emulsification activity, suggesting the
      production of biosurfactants. In antagonist assays, the supernatant showed
      antifungal activity against phytopathogenic fungi such as Penicillium expansum,
      Fusarium stilboides, Sclerotium rolfsii y Rhizoctonia solani, finding a reduction
      of mycelial growth of all fungi tested, ranging from 35 to 69%, this activity was
      increased with time of culture, accomplishing percentages of inhibition up to 85%
      with supernatants obtained at 72 h. Then, the crude biorsurfactant (CB) was
      isolated from the supernatant in order to assay its antagonistic effect on the
      phytopathogens previously tested, finding an increase in the inhibition up to 97%
      at 500 mg/L of CB. The composition of CB was determined by infrared spectroscopy,
      identifying various functional groups related to lipopeptides, which were
      purified by high-performance liquid chromatography and analyzed by MALDI-TOF/TOF
      MS, revealing a mixture of fengycins A and B whose high antifungal activity is
      been widely recognized. These results show that PGPR Bacillus sp. MA04 could also
      contribute to plant health status through the production of metabolites with
      antimicrobial activity.

PMID- 29651181
TI  - Extracellular Synthesis and Characterization of Gold Nanoparticles Using
      Mycobacterium sp. BRS2A-AR2 Isolated from the Aerial Roots of the Ghanaian
      Mangrove Plant, Rhizophora racemosa.
AB  - Through the use of genomes that have undergone millions of years of evolution,
      marine Actinobacteria are known to have adapted to rapidly changing environmental
      pressures. The result is a huge chemical and biological diversity among marine
      Actinobacteria. It is gradually becoming a known fact that, marine Actinobacteria
      have the capability to produce nanoparticles which have reasonable sizes and
      structures with possible applications in biotechnology and pharmacology.
      Mycobacterium sp. BRS2A-AR2 was isolated from the aerial roots of the mangrove
      plant Rhizophora racemosa. The Mycobacterium was demonstrated for the first time
      ever to produce AuNPs with sizes that range between 5 and 55 nm. The highest
      level absorbance of the biosynthesized AuNPs was typical for actinobacterial
      strains (2.881 at 545 nm). The polydispersity index was measured as 0.207 in DLS
      and the zeta potential was negatively charged (- 28.3 mV). Significant vibration
      stretches were seen at 3314, 2358, 1635 and 667 cm-1 in FT-IR spectra. This
      demonstrated the possible use of small aliphatic compounds containing -COOH, -OH,
      -Cl and -NH2 functional groups in the stabilization of the AuNPs. The effect of
      the biosynthesized AuNPs on HUVEC and HeLA cell lines was measured at 48 h. IC50
      values were determined at 3500 ug/ml concentration for HUVEC and HeLA cell lines
      at 45.25 and 53.41% respectively.

PMID- 29651182
TI  - First Report of a New Isolate of Metarhizium rileyi from Maize Fields of
      Quivican, Cuba.
AB  - Metarhizium rileyi (Farlow) Samson is an important entomopathogenic fungus of
      more than 30 species of Lepidoptera larvae. The aim of this research was to
      characterize isolate of M. rileyi from Quivican, Cuba on the basis of
      morphological and molecular approaches. The fungus was isolated from samples of
      S. frugiperda larvae collected from maize fields of Quivican municipality,
      Mayabeque province, Cuba, and it was cultured on PDA + Ampicillin solid media for
      morphological characterization. The DNA was isolated using CTAB method and
      internal transcribed spacer (ITS1, ITS4) were used as the primers for the
      amplification. The amplified products of 1335 bp were purified and sequenced at
      CINVESTAV-IPN in both the directions using the above primers. A consensus
      sequence was obtained by alignment of the forward and reverse sequences for this
      region and deposited in GenBank (MG637450). The fungus produced slightly cottony
      colony of pale green color and dispersed conidia and septal mycelium were
      observed under the optical microscope. A BLAST search of the sequence in GenBank
      revealed a 99% of identity with several strains of N. rileyi (e.g., AF368501.1,
      AB268359.1 and EU553337.1) and M. rileyi (e.g., KY436756.1). This is the first
      report of M. rileyi isolate from maize fields of Quivican in Cuba and this is
      important for biodiversity studies and is another possibility for Integrated Pest
      Management.

PMID- 29651183
TI  - Annotation and De Novo Sequence Characterization of Extracellular beta
      Fructofuranosidase from Penicillium chrysogenum Strain HKF42.
AB  - The genome of a fungal strain Penicillium chrysogenum strain HKF42, which can
      grow on 20% sucrose has been annotated for 7595 protein coding sequences. On
      mining of CAZymes, we could annotate a beta-fructofuranosidase gene responsible
      for fructo-oligosaccharides (FOS) synthesis which is a known prebiotic. The
      enzyme activity was demonstrated and validated with the generation of FOS as
      kestose and nystose.

PMID- 29651184
TI  - Psychrotolerant Sphingobacterium kitahiroshimense LT-2 Isolated from Dhundi
      Glacier, Himachal Pradesh: Origin Prediction and Future Application.
AB  - A psychrotolerant bacterium, isolated from Dhundi Glacier, Himachal Pradesh
      (India) was identified as Sphingobacterium kitahiroshimense LT-2 on the basis of
      biochemical, molecular and phylogenetic analysis. Sphingobacterium
      kitahiroshimense was first reported from Japan and was isolated from the city of
      Kitahiroshima, Hokkaido, Japan. In this report we have discussed about the origin
      of our strain and predicted that air masses and dust associated microbial cells
      transportation phenomena may be applicable for the origin of this species in this
      region. Enzymes and secondary metabolites secreted by the genus Sphingobacterium
      have enormous potentiality regarding their biotechnological application.
      Preliminary study of our strain based on metabolic profiling through HPLC showed
      many new metabolites were secreted by the bacterium when grown in presence of
      different sugar medium at 28  degrees C. As far as our knowledge this is the
      first report about Sphingobacterium species isolated from this region. This
      preliminary finding will help to draw an idea about the bacterial population in
      this Himalayan Glaciers (in HP) as well as biotechnological application of this
      strain can be explored further.

PMID- 29651185
TI  - Tackling Salmonella Persister Cells by Antibiotic-Nisin Combination via Mannitol.
AB  - Bacterial persisters (defined as dormant, non-dividing cells with globally
      reduced metabolism) are the major cause of recurrent infections. As they neither
      grow nor die in presence of antibiotics, it is difficult to eradicate these cells
      using antibiotics, even at higher concentrations. Reports of metabolites (which
      help in waking up of these inactive cells) enabled eradication of bacterial
      persistence by aminoglycosides, suggest the new potential strategy to improve
      antibiotic therapy. Here we propose, mannitol enabled elimination of Salmonella
      persister cells by the nisin-antibiotic combination. For this, persister cells
      were developed and characterized for their typical properties such as non
      replicative state and metabolic dormancy. Different carbon sources viz. glucose,
      glycerol, and mannitol were used, each as an adjunct to ampicillin for the
      eradication of persister cells. The maximum (but not complete) killing was
      observed with mannitol-ampicillin, out of all the combinations used. However,
      significant elimination (about 78%) could be observed, when nisin (an
      antimicrobial peptide) was used with ampicillin in presence of mannitol, which
      might have mediated the transfer of antibiotic-nisin combination at the same time
      when the cells tried to grab the carbon molecule. Further, the effectiveness of
      the trio was confirmed by flow cytometry. Overall, our findings highlight the
      potential of this trio-combination for developing it as an option for tackling
      Salmonella persister cells.

PMID- 29651186
TI  - In-Vitro Activity of Doxycycline and beta-Lactam Combinations Against Different
      Strains of Burkholderia pseudomallei.
AB  - Although doxycycline is active against Burkholderia pseudomallei and has been
      used in the eradication stage of melioidosis therapy, it is not regularly used
      during the initial intensive phase. In order to assess its potential use in
      intensive phase therapy, we investigated in vitro pharmacodynamic activity of
      doxycycline and beta-lactams alone and in combination against four Malaysian
      strains of B. pseudomallei. Using a checkerboard assay, the combinations of
      doxycycline and imipenem, doxycycline and ceftazidime, and doxycycline and
      amoxicillin-clavulanate tested against four strains showed indifferent effects
      with summation fractional inhibitory concentration values ranging from 0.62 to
      2.12. Time-kill experiments also indicated that the combinations of
      doxycycline/beta-lactam antibiotics against four tested strains did not fulfil
      synergy criteria, in which all combinations showed indifferent effects with -
      1.36 to 1.26-log CFU/mL compared to the most active monotherapy regimen in each
      combination. No re-growth of bacteria was detected after the early killing in
      doxycycline/beta-lactam combination regimens compared to beta-lactam monotherapy
      regimens, in which 9 out of 10 were associated with re-growth of bacteria. As no
      synergistic activity was observed, this in vitro study showed that doxycycline
      offers no additional benefit to be used in combination with beta-lactams in the
      intensive phase of therapy.

PMID- 29651187
TI  - Effect of Encapsulation on Viability of Bifidobacterium longum CFR815j and
      Physiochemical Properties of Ice Cream.
AB  - The health beneficial attributes of bifidobacteria and its safe association with
      the host gut has increased its significance as a probiotic. However delivering
      probiotic bifidobacteria with Minimum Biological Value (MBV) through product has
      always been a challenge. In the present study, an attempt was made to maintain
      the viability of native isolate of Bifidobacterium longum CFR 815j and deliver
      through ice-cream. B. longum CFR815j was microencapsulated in alginate starch
      capsules by emulsification followed by evaluation of bead stability in simulated
      gastrointestinal conditions. After incorporation in ice-cream, the effect on
      chemical properties, sensory parameters and meltdown characteristics of the
      product were also evaluated. Survival studies of B. longum revealed higher counts
      than 107 in the product which is essential for probiotic bacteria to exhibit
      beneficial effect. Further, all the properties of this ice-cream were comparable
      to the regular ice-cream. Our studies conclude that encapsulation was able to
      maintain the requisite MBV of bifidobacteria in ice-cream without affecting the
      sensory characteristics.

PMID- 29651188
TI  - Integrated Artificial Intelligence Approaches for Disease Diagnostics.
AB  - Mechanocomputational techniques in conjunction with artificial intelligence (AI)
      are revolutionizing the interpretations of the crucial information from the
      medical data and converting it into optimized and organized information for
      diagnostics. It is possible due to valuable perfection in artificial
      intelligence, computer aided diagnostics, virtual assistant, robotic surgery,
      augmented reality and genome editing (based on AI) technologies. Such techniques
      are serving as the products for diagnosing emerging microbial or non microbial
      diseases. This article represents a combinatory approach of using such approaches
      and providing therapeutic solutions towards utilizing these techniques in disease
      diagnostics.

PMID- 29651189
TI  - Physical Activity and Personality Development over Twenty Years: Evidence from
      Three Longitudinal Samples.
AB  - A physically inactive lifestyle is associated with maladaptive patterns of
      personality development over relatively short follow-up periods. The present
      study extends existing research by examining whether this association persists
      over 20 years. Participants (total N = 8,723) were drawn from the Wisconsin
      Longitudinal Study Graduates and Siblings samples and the Midlife in the United
      States Study. Controlling for demographic factors and disease burden, baseline
      physical inactivity was related to steeper declines in conscientiousness in all
      three samples and a meta-analysis (beta=-.06). The meta-analysis further showed
      that lower physical activity was associated with declines in openness (beta=
      .05), extraversion (beta=-.03), and agreeableness (beta=-.03). These findings
      provide evidence that a physically inactive lifestyle is associated with long
      term detrimental personality trajectories.

PMID- 29651190
TI  - Where in the world is the world heading?

PMID- 29651192
TI  - Correlations for the Dielectric Constants of H2S, SO2, and SF6.
AB  - A new method is developed for correlating the static dielectric constant of polar
      fluids over wide ranges of conditions where few experimental data exist.
      Molecular dynamics simulations are used to establish the temperature and density
      dependence of the Kirkwood g-factor, and also the functional form for the
      increase of the effective dipole moment with density. Most parameters in the
      model are obtained entirely from simulation; a single proportionality constant is
      adjusted to obtain agreement with the limited experimental data. The method is
      applied to hydrogen sulfide (H2S) and sulfur dioxide (SO2), both of which are
      important in geochemistry but have only a few dielectric data available. The
      resulting correlations agree well with the available liquid data, obey physical
      boundary conditions at low density and at high temperature, and interpolate in
      density and temperature in a physically reasonable manner. In addition, we
      present a more conventional correlation for the dielectric constant of sulfur
      hexafluoride, SF6, where more data are available.

PMID- 29651191
TI  - Nonstandard Work Schedules, Family Dynamics, and Mother-Child Interactions During
      Early Childhood.
AB  - The rising number of parents who work nonstandard schedules has led to a growing
      body of research concerned with what this trend means for children. The negative
      outcomes for children of parents who work nonstandard schedules are thought to
      arise from the disruptions these schedules place on family life, and thus, the
      types of parenting that support their children's development, particularly when
      children are young. Using a nationally representative sample of two-parent
      families (Early Childhood Longitudinal Study-Birth cohort, n = 3,650), this study
      examined whether mothers' and their partners' nonstandard work schedules were
      associated with mothers' parenting when children were 2 and 4 years old.
      Structural equation models revealed that mothers' and their partners' nonstandard
      work schedules were associated with mothers' lower scores on measures of positive
      and involved parenting. These associations were mediated by fathers' lower levels
      of participation in cognitively supportive parenting and greater imbalance in
      cognitively supportive tasks conducted by mothers versus fathers.

PMID- 29651193
TI  - Using New Technologies for Time Diary Data Collection: Instrument Design and Data
      Quality Findings from a Mixed-Mode Pilot Survey.
AB  - Recent years have witnessed a steady growth of time-use research, driven by the
      increased research and policy interest in population activity patterns and their
      associations with long-term outcomes. There is recent interest in moving beyond
      traditional paper-administered time diaries to use new technologies for data
      collection in order to reduce respondent burden and administration costs, and to
      improve data quality. This paper presents two novel diary instruments that were
      employed by a large-scale multi-disciplinary cohort study in order to obtain
      information on the time allocation of adolescents in the United Kingdom. A web
      administered diary and a smartphone app were created, and a mixed-mode data
      collection approach was followed: cohort members were asked to choose between
      these two modes, and those who were unable or refused to use the web/app modes
      were offered a paper diary. Using data from a pilot survey of 86 participants, we
      examine diary data quality indicators across the three modes. Results suggest
      that the web and app modes yield an overall better time diary data quality than
      the paper mode, with a higher proportion of diaries with complete activity and
      contextual information. Results also show that the web and app modes yield a
      comparable number of activity episodes to the paper mode. These results suggest
      that the use of new technologies can improve diary data quality. Future research
      using larger samples should systematically investigate selection and measurement
      effects in mixed-mode time-use survey designs.

PMID- 29651195
TI  - Impacts of plastic film mulching on crop yields, soil water, nitrate, and organic
      carbon in Northwestern China: A meta-analysis.
AB  - In order to increase crop yield in semi-arid and arid areas, plastic film
      mulching (PFM) is widely used in Northwestern China. To date, many studies have
      addressed the effects of PFM on soil physical and biochemical properties in rain
      fed agriculture in Northwestern China, but the findings of different studies are
      often contradictory. Therefore, a comprehensive review of the impacts of PFM on
      soil water content, soil nutrients and food production is needed. We compiled the
      results of 1278 observations to evaluate the overall effects of PFM on soil water
      content, the distribution of nitrate and soil organic carbon, and crop yield in
      rain-fed agriculture in Northwestern China. Our results showed that PFM increased
      soil moisture and nitrate concentration in topsoils (0-20 cm) by 12.9% and 28.2%,
      respectively, but slightly decreased (1.8%) soil organic carbon (SOC) content in
      the 0-10 cm soil layer. PFM significantly increased grain yields by 43.1%, with
      greatest effect in spring maize (79.4%). When related to cumulative precipitation
      during the crop growing season, yield increase from PFM was greatest (72.8%) at
      200-300 mm, which was attributed to the large increase for spring maize and
      potato, implying that crop zoning would be beneficial for PFM in this region.
      When related to N application rate, crop yields benefited most from PFM (80.2%)
      at 200-300 kg/ha. A cost-benefit analysis indicated that PFM increased economic
      return by an average of 29.5%, with the best improvement for spring maize (71.1%)
      and no increase for spring wheat. In conclusion, PFM can significantly increase
      crop yield and economic return (especially for spring maize) in rain-fed
      agriculture areas of Northwestern China. Crop zoning is recommended for PFM to
      achieve the largest economic benefit. However, full account needs to be taken of
      the environmental impacts relating to N loss, SOC depletion and film pollution to
      evaluate the sustainability of PFM systems and further research is required to
      quantify and mitigate these impacts.

PMID- 29651196
TI  - Resolving Alliance Ruptures from an Attachment-Informed Perspective.
AB  - In this article, we examine how the different attachment patterns enable or
      hinder the resolution of ruptures in the therapeutic alliance. We try to show
      that secure and insecure patients alike may experience ruptures in the
      therapeutic alliance, but that their ability to participate in resolving such
      ruptures differ markedly. Recent findings with the Patient Attachment Coding
      System (PACS) show that attachment classifications manifest in psychotherapy as
      distinct ways of communicating about present internal experience. Secure patients
      disclose their present experience openly and invite attunement from the
      therapist, while insecure patients either minimize their contributions to the
      dialogue (avoidant) or the contributions of the therapist (preoccupied). Using
      examples from session transcripts, we demonstrate how secure patients are
      particularly responsive to resolution strategies that focus on here-and-now
      experience, while insecure patients' characteristic ways of communicating pose
      significant challenges to the resolution process.

PMID- 29651197
TI  - A Strategy for Sperm Cryopreservation of Atlantic Salmon, Salmo salar, for Remote
      Commercial-scale High-throughput Processing.
AB  - Sperm cryopreservation is an essential tool for long-term storage of genetic
      resources for aquaculture fishes. The goal of this study was to develop an
      efficient and streamlined protocol for high-throughput processing for sperm
      cryopreservation in Atlantic salmon, Salmo salar. The objectives were to
      evaluate: 1) osmolality of blood serum for determining extender osmolality; 2)
      effects of extenders for fresh sperm dilution and refrigerated storage; 3)
      effects of methanol and dimethyl sulfoxide (DMSO) on fresh sperm motility, and 4)
      motility and fertility after thawing. In this study, sperm samples were collected
      at a hatchery site in Canada, and shipped to a freezing site located 2200 miles
      (3550 km) away in the United States. Evaluation of three extenders indicated that
      Mounib solution was suitable for diluting dry sperm for sample processing. Ten
      percent of methanol or DMSO was less toxic to sperm cells than was 15% within 30
      min. Further testing with methanol at 5, 10, and 15%, and sperm solution:extender
      dilutions (v:v) of 1:1, 1:3, 1:19 (at concentrations of ~5*107; 3*108, and 1*109
      cells/mL) indicated that methanol at 5% and 10% showed less toxicity to fresh
      sperm within 1 hr at sperm: extender dilutions of 1:1 and 1:3. Post-thaw motility
      of sperm cryopreserved with 10% methanol was significantly higher than that with
      10% DMSO, and fertility reflected those results (0-1% in DMSO vs. 38-55% in
      methanol). Further evaluation of sperm cryopreservation with 10 and 15% methanol
      at sperm dilution ratios of 1:1, 1:3, 1:19 indicated post-thaw motility in 10%
      methanol was significantly higher than that in 15% methanol, and post-thaw
      fertility in 10% methanol at 1:1 and 1:3 dilution ratios had fertilization rates
      similar to that of fresh sperm controls. Sperm samples from 12 males
      cryopreserved with 10% methanol showed male-to-male variation in post-thaw
      motility (0-36%). Overall, a simplified standard protocol was established for
      cryopreservation of shipped sperm of Atlantic salmon using extender without egg
      yolk and yielded satisfactory post-thaw motility and fertilization rates. This
      procedure can be readily adopted by aquaculture facilities to take advantage of
      high-throughput cryopreservation capabilities at remote service centers. Most
      importantly, this approach lays the groundwork for an alternative commercial
      model for commercial-scale production, quality control and development of
      industrial standards. Control of male variability and sperm quality remain
      important considerations for future work.

PMID- 29651198
TI  - Silver Nitrate Grade and Its Effect on Physical Developer Performance-A
      Validation Study.
AB  - Silver nitrate is a critical component of the physical developer (PD) reagent.
      Significant increases in the cost of silver nitrate in recent years have caused
      the United States Secret Service's Forensic Laboratory to look for a more
      economical way to produce physical developer. One possible solution to this
      dilemma is to use a lower grade of silver nitrate, which typically has a lower
      cost. This study compared the quality of fingerprints produced on various paper
      substrates by three physical developer working solutions, each prepared using
      either the American Chemical Society (ACS), U.S. Pharmacopeia (USP), or technical
      grade of silver nitrate. It was determined that the less pure grades of silver
      nitrate produced approximately the same quality of fingerprints as the ACS grade,
      which is currently used in the authors' laboratory for making PD working
      solutions. In the experiments comparing PD prepared using the ACS and USP grades
      of silver nitrate, the ACS grade was superior only 5% of the time, whereas the
      USP grade was chosen 27% of the time. In the experiments comparing PD prepared
      using the ACS and technical grades of silver nitrate, the ACS grade was superior
      only 10% of the time, whereas the technical grade was selected 17% of the time.
      For the majority of the sample comparisons, no difference in fingerprint quality
      was observed. The overall conclusion was that either USP or technical grade
      silver nitrate can be used in place of the current, and more expensive, ACS grade
      of silver nitrate.

PMID- 29651194
TI  - River networks as ecological corridors: A coherent ecohydrological perspective.
AB  - This paper draws together several lines of argument to suggest that an
      ecohydrological framework, i.e. laboratory, field and theoretical approaches
      focused on hydrologic controls on biota, has contributed substantially to our
      understanding of the function of river networks as ecological corridors. Such
      function proves relevant to: the spatial ecology of species; population dynamics
      and biological invasions; the spread of waterborne disease. As examples, we
      describe metacommunity predictions of fish diversity patterns in the Mississippi
      Missouri basin, geomorphic controls imposed by the fluvial landscape on
      elevational gradients of species' richness, the zebra mussel invasion of the same
      Mississippi-Missouri river system, and the spread of proliferative kidney disease
      in salmonid fish. We conclude that spatial descriptions of ecological processes
      in the fluvial landscape, constrained by their specific hydrologic and ecological
      dynamics and by the ecosystem matrix for interactions, i.e. the directional
      dispersal embedded in fluvial and host/pathogen mobility networks, have already
      produced a remarkably broad range of significant results. Notable scientific and
      practical perspectives are thus open, in the authors' view, to future
      developments in ecohydrologic research.

PMID- 29651199
TI  - Modification of Nanoporous Silicon Nitride with Stable and Functional Organic
      Monolayers.
AB  - This study describes the formation of functional organic monolayers on thin,
      nanoporous silicon nitride membranes. We demonstrate that the vapor-phase carbene
      insertion into the surface C-H bonds can be used to form sub-5 nm molecular
      coatings on nanoporous materials, which can be further modified with monolayers
      of polyethylene glycol (PEG) molecules. We investigate composition, thickness,
      and stability of the functionalized monolayers and the changes in the membrane
      permeability and pore size distribution. We show that, due to the low coating
      thickness (~7 nm), the functionalized membrane retains 80% of the original gas
      permeance and 40% of the original hydraulic permeability. We also show that the
      carbene/PEG functionalization is hydrolytically stable for up to 48 h of exposure
      to water and that it can suppress nonspecific adsorption of the proteins BSA and
      IgG. Our results suggest that the vapor-phase carbenylation can be used as a
      complementary technology to the traditional self-assembly and polymer brush
      chemistries in chemical functionalization of nanoporous materials, which are
      limited in their ability to serve as stable coatings that do not occlude
      nanomembrane pores.

PMID- 29651200
TI  - Return to illicit drug use post-incarceration among formerly incarcerated Black
      Americans.
AB  - Aims: The number of drug dependent individuals incarcerated in the U.S. is
      exceptionally high, and reportedly 60 percent of incarcerated Black Americans
      have a substance abuse disorder. The purpose of this study was to identify
      factors associated with return to illicit drug use post-incarceration. Methods: A
      cross-sectional study was conducted with 121 formerly incarcerated Black
      Americans in New York City to examine predictors of return to illicit drug use.
      Kaplan-Meier curves were generated on the outcome of time-to-drug use for various
      predictors and compared using the log-rank test. Cox proportional hazards models
      were used to identify significant predictors of return to illicit drug use post
      incarceration. Findings: Approximately 83 percent (n=100) of the participants
      reported a history of illicit drug use, not including participants who have only
      used marijuana. Out of 121 participants, 36 (29.8%) had used drugs within one day
      after release. By two weeks after release, half had used drugs. Gender and
      history of heroin use were significant predictors of time-to-drug use according
      to the log rank test. Conclusions: The potential for immediate return to drug use
      among our sample suggests that discharge support programs that focus specifically
      on healthy decision-making among women and heroin users are especially critical.

PMID- 29651201
TI  - Tissue-Resident Memory Cells: New Marked Shield to Fight Cancers.

PMID- 29651202
TI  - A Narrative Review of Potential Future Antidiabetic Drugs: Should We Expect More?
AB  - Prevalence of diabetes mellitus, a chronic metabolic disease characterized by
      hyperglycemia, is growing worldwide. The majority of the cases belong to type 2
      diabetes mellitus (T2DM). Globally, India ranks second in terms of diabetes
      prevalence among adults. Currently available classes of therapeutic agents are
      used alone or in combinations but seldom achieve treatment targets. Diverse
      pathophysiology and the need of therapeutic agents with more favourable
      pharmacokinetic-pharmacodynamics profile make newer drug discoveries in the field
      of T2DM essential. A large number of molecules, some with novel mechanisms, are
      in pipeline. The essence of this review is to track and discuss these potential
      agents, based on their developmental stages, especially those in phase 3 or phase
      2. Unique molecules are being developed for existing drug classes like insulins,
      DPP-4 inhibitors, GLP-1 analogues; and under newer classes like dual/pan PPAR
      agonists, dual SGLT1/SGLT2 inhibitors, glimins, anti-inflammatory agents,
      glucokinase activators, G-protein coupled receptor agonists, hybrid peptide
      agonists, apical sodium-dependent bile acid transporter (ASBT) inhibitors,
      glucagon receptor antagonists etc. The heterogeneous clinical presentation and
      therapeutic outcomes in phenotypically similar patients is a clue to think beyond
      the standard treatment strategy.

PMID- 29651204
TI  - Ameliorative Effects of Allium sativum Extract on iNOS Gene Expression and NO
      Production in Liver of Streptozotocin + Nicotinamide-Induced Diabetic Rats.
AB  - Diabetes mellitus (DM) is one of the most prevalent diseases in the world, which
      is strongly associated with liver dysfunction. Hyperglycemia, through an
      oxidative stress pathway, damages various tissues. Herbal medicine is a good
      candidate to ameliorate hyperglycemia and oxidative stress. In this study, the
      effects of aqueous Allium sativum (garlic) extract (AGE) on gene expression of
      inducible nitric oxide synthases (iNOS) and production of nitric oxide (NO) were
      evaluated in the liver tissue of diabetic rats. Four groups of rats contained
      normal control rats, garlic control rats (AGE), Streptozotocin (STZ) +
      nicotinamide-induced diabetic rats (DM), and diabetic rats treated with garlic
      (DM + AGE). Glucose levels and liver enzymes activities were determined by
      colorimetric assay in the serum. Gene expression of iNOS by real-time PCR, NO
      levels by Griess method, oxidative stress parameters by spectrophotometric method
      and histopathological examination by hematoxylin and eosin staining method were
      evaluated in the liver tissues. Glucose levels, activities of liver enzymes,
      oxidative stress markers, iNOS gene expression, and NO production increased
      significantly in diabetic rats in comparison with control rats, whereas after
      oral administration of garlic, these parameters decreased significantly, close to
      the normal levels. Hence, the beneficial effects of garlic on the liver injury of
      diabetes could be included in the hypoglycaemic and antioxidant properties of
      garlic via a decrease in gene expression of iNOS and subsequent NO production.

PMID- 29651203
TI  - Lead: Tiny but Mighty Poison.
AB  - The documentation of lead toxicity (plumbism) dates back to the times when man
      learnt its various applications. This versatile heavy metal is non-degradable and
      its ability to get accumulated in the body that goes undiagnosed, makes it a
      serious environmental health hazard. Lead is now known to affect almost every
      organ/tissue of the human body. With irreversible effects on neurobiological
      development of young children and foetus, its toxicity has lasting implications
      on the human life. Outlining the symptoms, diagnosis and treatment therapy for
      lead poisoning, the present review elaborates the pathophysiological effects of
      lead on various organs. This will be of immense help to the health professionals
      so as to inculcate a better understanding of the lead poisoning which otherwise
      is asymptomatic. With chelation therapy being the classic path of treatment, new
      strategies are being explored as additive/adjunct therapy. It is now understood
      that lead toxicity is completely preventable. In this regard significant efforts
      are in place in the developed countries whereas much needs to be done in the
      developing countries. Spreading the awareness amongst the masses by educating
      them and reducing the usage of lead following stricter industry norms appears to
      be the only roadmap to prevent lead poisoning. Efforts being undertaken by the
      Government of India and other organisations are also mentioned.

PMID- 29651205
TI  - Errors in the Extra-Analytical Phases of Clinical Chemistry Laboratory Testing.
AB  - The total testing process consists of various phases from the pre-preanalytical
      to the post-postanalytical phase, the so-called brain-to-brain loop. With
      improvements in analytical techniques and efficient quality control programmes,
      most laboratory errors now occur in the extra-analytical phases. There has been
      recent interest in these errors with numerous publications highlighting their
      effect on service delivery, patient care and cost. This interest has led to the
      formation of various working groups whose mission is to develop standardized
      quality indicators which can be used to measure the performance of service of
      these phases. This will eventually lead to the development of external quality
      assessment schemes to monitor these phases in agreement with ISO15189:2012
      recommendations. This review focuses on potential errors in the extra-analytical
      phases of clinical chemistry laboratory testing, some of the studies performed to
      assess the severity and impact of these errors and processes that are in place to
      address these errors. The aim of this review is to highlight the importance of
      these errors for the requesting clinician.

PMID- 29651206
TI  - Urinary Urea, Uric Acid and Hippuric Acid as Potential Biomarkers in Multiple
      Sclerosis Patients.
AB  - Urine is a proven source of metabolite biomarkers and has the potential to be a
      rapid, noninvasive, inexpensive, and efficient diagnostic tool for various human
      diseases. Despite these advantages, urine is an under-investigated source of
      biomarkers for multiple sclerosis (MS). The objective was to investigate the
      level of some urinary metabolites (urea, uric acid and hippuric acid) in patients
      with MS and correlate their levels to the severity of the disease, MS subtypes
      and MS treatment. The urine samples were collected from 73 MS patients-48 with
      RRMS and 25 with SPMS- and age matched 75 healthy controls. The values of urinary
      urea, uric acid and hippuric acid in MS patients were significantly decreased,
      and these metabolites in SPMS pattern showed significantly decrease than RRMS
      pattern. Also showed significant inverse correlation with expanded disability
      status scale and number of relapses. Accordingly, they may act as a potential
      urinary biomarkers for MS, and correlate to disease progression.

PMID- 29651207
TI  - Protective Effect of Allyl Isothiocyanate on Glycoprotein Components in 7,12
      dimethylbenz(a)anthracene Induced Mammary Carcinoma in Rats.
AB  - The present study aimed to investigate the protective effect of allyl
      isothiocyanate (AITC) on glycoprotein components in 7,12
      dimethylbenz(a)anthracene (DMBA) induced mammary carcinogenesis in female Sprague
      Dawley rats. Mammary tumor was induced by a single dose of DMBA (25 mg/rat)
      injected subcutaneously near mammary gland. The levels of glycoprotein components
      such as hexose, hexosamine and sialic acid were analyzed colorimetrically in
      plasma, mammary and liver tissues. We observed an increased levels of
      glycoprotein components in plasma, mammary and liver tissues in cancer bearing
      rats. It was further confirmed by Periodic Acid Schiff staining in mammary and
      liver tissues. Upon oral administration of AITC to DMBA injected rats, the
      abnormal changes were reverted back to near normal levels and biochemical
      findings are supported by histological analysis. This could be due to the anti
      neoplastic potential of AITC against DMBA-induced mammary carcinogenesis. The
      result shows that AITC has the potential to inhibit abnormal glycosylation that
      favors neoplastic transformation.

PMID- 29651210
TI  - Effects of Alternanthera sessilis on Liver Function in Carbon Tetra Chloride
      Induced Hepatotoxicity in Wister Rat Model.
AB  - Alternanthera sessilis commonly known as 'sessile joy weed' or 'dwarf copperleaf'
      is found throughout the hotter parts of India up to an altitude of 1200 m2. In
      Assam, the plant has been traditionally used in the treatment of jaundice along
      with other ailments. The study focuses primarily on the evaluation of
      hepatoprotective activity of the plant with special references to its putative
      protective role in carbon tetrachloride induced liver injury on Wister albino
      rat. The in vivo hepatoprotective activity of the methanolic extract at the dose
      of 250 mg/kg body weight was highly effective in controlling SGPT, SGOT, ALP,
      serum cholesterol and serum bilirubin level as compared to silymarin. The said
      extract also significantly lowered the lipid profile caused by CCl4. The activity
      shown by methanolic extract of the whole plant of A. sessilis is of considered
      importance and thus justified its use in controlling hepatic diseases in
      traditional treatment system.

PMID- 29651209
TI  - Polymorphic Variation in Double Strand Break Repair Gene in Indian Population: A
      Comparative Approach with Worldwide Ethnic Group Variations.
AB  - DNA repair capacity is essential in maintaining cellular functions and
      homeostasis. Identification of genetic polymorphisms responsible for reduced DNA
      repair capacity may allow better cancer prevention. Double strand break repair
      pathway plays critical roles in maintaining genome stability. Present study was
      conducted to determine distribution of XRCC3 Exon 7 (C18067T, rs861539) and XRCC7
      Intron 8 (G6721T, rs7003908) gene polymorphisms in North Indian population and
      compare with different populations globally. The genotype assays were performed
      in 224 normal healthy individuals of similar ethnicity using the polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP). Allelic frequencies
      of wild type were 79% (C) in XRCC3 Exon 7 C > T and 57% (G) in XRCC7 Intron 8 (G
      > T) 57% (G) observed. On the other hand, the variant allele frequency were 21%
      (T) in XRCC3 Exon 7 C > T and 43% (T) in XRCC7 Intron 8 G > T respectively. Major
      differences from other ethnic populations were observed. Our results suggest that
      frequency in these DNA repair genes exhibit distinctive pattern in India that
      could be attributed to ethnicity variation. This could assist in high-risk
      screening of humans exposed to environmental carcinogens and cancer
      predisposition in different ethnic groups.

PMID- 29651208
TI  - Role of Brain Biomarker in Predicting Clinical Outcome in Hypertensive
      Cerebrovascular Ischemic Stroke.
AB  - This study was undertaken to evaluate the role of serum neuron specific enolase
      (NSE) in prediction of disability and neurological worsening in hypertensive
      ischemic cerebrovascular stroke. 80 hypertensive ischemic stroke patients
      diagnosed by a neurologist as per WHO definition along with radiological findings
      suggestive of cerebrovascular stroke and differentiating from hemorrhagic stroke
      and 60 controls having essential hypertension coming to hospital because of
      regular checkup or headache but with no neurological disease were included in the
      study. Neurological disability was assessed by NIHSS at the time of admission
      (within 72 h from the onset of stroke) and on 7th day after admission and cases
      were categorized into mild, moderate and severe disability. Venous blood samples
      were drawn within 72 h from the onset of symptoms. The samples were processed as
      per the laboratory protocol. The serum NSE samples were analyzed using an enzyme
      immunoassay based on the sandwich technique. We observed raised serum NSE in
      hypertensive ischemic stroke (17.4 +/- 5.4 ng/ml) with significant association
      between different hypertensive groups than in hypertensive controls (9.1 +/- 0.75
      ng/ml). Greater degree of disability was observed in hypertensive stroke patients
      with raised serum NSE and hypertensive patients with mean serum NSE level of 22.9
      +/- 3.6 ng/ml and dyslipidemia had greater probability of neurological worsening
      as compared to those with mean serum NSE level of 12.7 +/- 1.2 ng/ml. Serum NSE
      levels can serve as a peripheral indicator of neuronal damage and assist in the
      prediction of disability and clinical outcome in hypertensive cerebrovascular
      ischemic stroke patients.

PMID- 29651212
TI  - Correlation Between Intron 4 Polymorphism of the Endothelial Nitric Oxide
      Synthase Gene and Cardiovascular Risk with the Numbers of Circulating Endothelial
      Progenitor Cells in Healthy Subjects.
AB  - In the present study, we investigated the relationship between an important 27 bp
      repeat polymorphism in intron 4 of eNOS and numbers of circulating EPCs in
      presence of cardiovascular disease (CVD) risk factors in a group of healthy human
      volunteers. The study comprised of 45 healthy subjects (30-50 years). These
      subjects had various degrees of CVD risk but no history of CVD. The repeat
      polymorphism of eNOS was detected by polymerase chain reaction and EPC levels
      were analyzed by flow cytometry. We observed a good association between the
      intronic 4 mutant a/b genotype and the combined Framingham risk factor score in
      our subjects (chi2 = 3.2, P = 0.07). EPC numbers in subjects with mutant eNOS a/b
      genotype were also less than those observed in subjects with normal eNOS b/b
      genotype (P = 0.06). Interestingly, subjects with eNOS a/b genotype showed a
      significant inverse correlation between framingham risk score and EPC numbers (R
      = -0.57, P < 0.05). The study suggests that the presence of CVD risk factors in
      subjects with eNOS intron 4 polymorphism results in reduced number of circulating
      EPCs, which may significantly predispose them to CVD and aberrant endothelial
      repair.

PMID- 29651213
TI  - Genetic Polymorphism of CYP2C9 Among Sistani Ethnic Group in Gorgan.
AB  - Cytochrome P450 2C9 (CYP2C9) is involved in metabolism of many important drugs
      and its genotype variations is thought to affect drug efficacy and the treatment
      process. The aim of this study was to assess the distribution of CYP2C9 allele
      and genotypic variants in Sistani ethnic group, living in Gorgan, South East of
      Caspian Sea and North East of Iran. This study included 140 Sistani, referred to
      the health center of Gorgan. CYP2C9 genotyping was carried out by polymerase
      chain reaction-restriction fragment length polymorphism technique. The allele
      frequency of CYP2C9*1, CYP2C9*2 and CYP2C9*3 was 76.1, 16.1 and 7.8%,
      respectively. The frequency of CYP2C9*1/*1, CYP2C9*1/*2, CYP2C9*1/*3,
      CYP2C9*2/*2, CYP2C9*2/*3 and CYP2C9*3/*3 genotypes was 53.9, 22.1, 11.4, 2.9,
      4.3% and nil, respectively. In this study the genotypic variations of the CYP2C9
      allele among the Sistani ethnic group was investigated and great differences were
      observed in comparison to other populations. Our findings suggest that different
      genotypes of CYP2C9 may influence the pharmacokinetics of some drugs. More
      studies on the pharmacokinetic effects of CYP2C9 genotypes may help physicians
      choose optimal dosage of some drugs for treatment and prevention of their side
      effects. Since different ethnic groups from all over the world use medications,
      it suggests to investigate the pharmacokinetic effects of CYP2C9 genotypes in
      different populations.

PMID- 29651211
TI  - Study of the Effect of Bisphenol A on Oxidative Stress in Children with Autism
      Spectrum Disorders.
AB  - The role of bisphenol A (BPA) in autism was investigated in 49 children (mean age
      = 5.950 +/- 1.911 years) with autism spectrum disorders (ASDs) and 40 comparable
      age and sex matched children used as controls (mean age = 5.333 +/- 2.279 years).
      In addition, 8-Hydroxydeoxyguanosine (8-oxodG) was also studied as a biomarker of
      oxidative stress in the same set of two selected groups. The results showed that
      both BPA and 8-oxodG were significantly higher in children with autism than those
      of control children (p values = 0.025 and 0.0001, respectively). There were
      positive correlations between both BPA and 8-oxodG with ASDs severity (r = 0.400
      and 0.805, respectively), these correlations were highly significant (p values =
      0.004 and 0.001, respectively). There was a significance positive correlation
      between BMI and BPA, but the correlation between BMI and 8-oxodG was not
      significant in children with autism. The observed results revealed that BPA may
      increase oxidative stress resulting in mitochondrial dysfunction that affecting
      the behavior and functioning of ASDs children.

PMID- 29651214
TI  - Homeostatic Model Assessment-Insulin Resistance (HOMA-IR 2) in Mild Subclinical
      Hypothyroid Subjects.
AB  - Despite various studies with conflicting results, the effect of thyroid hormones
      on lipids and insulin levels in dysthyroidism is of great interest. This case
      control study was aimed to perceive the existence of IR and dyslipidemia in mild
      subclinical hypothyroid subjects (TSH <= 9.9 uIU/ml) as compared to their age and
      gender matched euthyroid controls. Basic demographic information like height,
      weight was recorded. Serum samples of all the subjects were assayed for thyroid
      profile, lipid profile, blood glucose, HbA1C and insulin. BMI and insulin
      resistance was calculated. Compared to controls patients with mild subclinical
      hypothyroidism demonstrated hyperinsulinemia and dyslipidemia observed by the
      higher LDL cholesterol. A significantly positive correlation was observed for
      HOMA-IR with TSH and LDL cholesterol. Hence, even in the mild subclinical
      hypothyroid state assessment of thyroid function should be combined with
      estimation of plasma glucose, insulin and serum lipids to monitor and prevent its
      associated effects.

PMID- 29651215
TI  - Plasma Neutrophil Elastase, alpha1-Antitrypsin, alpha2-Macroglobulin and
      Neutrophil Elastase-alpha1-Antitrypsin Complex Levels in patients with Dengue
      Fever.
AB  - Dengue fever (DF) is characterized by systemic inflammatory response including
      neutrophil activation leading to uncontrolled elastase activity. This study was
      aimed to measure the activity of plasma neutrophil elastase (NE), its endogenous
      inhibitors alpha1-antitrypsin (alpha1-AT) and alpha2-macroglobulin (alpha2-MG)
      and elastase in complex with alpha1-AT (NE-alpha1-AT complex) in DF. 50 dengue
      patients [39 DF and 11 dengue hemorrhagic fever (DHF)] and 52 healthy subjects
      were included in the study. NE was measured using N-succinyl-tri-alanine-p
      nitroanilide as substrate. alpha1-AT, alpha2-MG and NE-alpha1-AT complex were
      estimated by ELISA. The result analysis indicated that the dengue patients had
      significantly higher elastase activity with significantly reduced inhibitor
      levels compared to controls. Between DF and DHF patients, DHF group had
      significantly higher elastase activity. In conclusion, significantly elevated NE
      and reduced inhibitors level in dengue fever indicate these parameters could be
      of significance in DF particularly for the assessment of progression of
      inflammatory processes.

PMID- 29651216
TI  - Linear Analysis of Autonomic Activity and Its Correlation with Creatine Kinase-MB
      in Overt Thyroid Dysfunctions.
AB  - Autonomic activity may be deranged in thyroid dysfunctions and may lead to
      cardiovascular morbidity and mortality. Myopathy is a common manifestation in
      thyroid disorders and may be associated with raised serum creatine kinase (CK).
      We hypothesized that cardiovascular abnormality in thyroid dysfunction may
      manifest as raised CK-MB. This study was designed to investigate the correlation
      of CK and its isoform CK-MB with thyroid profile and linear parameters of heart
      rate variability (HRV). The study was conducted on 35 hypothyroid and
      hyperthyroid patients each, and 25 age-matched healthy controls. Autonomic
      activity was assessed by simple short term 5-min HRV. Biochemical evaluation of
      serum thyroid profile, CK-NAC and CK-MB were estimated in all the subjects. Our
      results demonstrated low HRV in hypo- as well as hyperthyroid patients. We
      observed significantly higher serum CK levels in hypothyroid patients when
      compared to hyperthyroids and controls. However, no significant differences were
      observed in CK-MB levels in the three groups. Significant positive correlation of
      CK with TSH and negative correlation with some HRV parameters (LF power, HF
      power, total power, SDNN, RMSSD) was observed in hypothyroid patients. Whereas
      correlation of CK-MB with thyroid profile as well as HRV parameters was non
      significant in all the groups. Based on the CK and CK-MB findings and their
      correlation, we conclude that the cardiovascular changes seen in thyroid
      dysfunctions may primarily be due to autonomic imbalance without apparent cardiac
      muscle involvement. Whereas, raised CK levels indicate predominantly skeletal
      muscle involvement in hypothyroid patients.

PMID- 29651217
TI  - Coinheritance of Sicilian (deltabeta)0-Thalassemia and Two Rare Hemoglobin
      Variants: A Complex Case of Hemoglobinopathy.
AB  - alpha-Thalassemia (alpha-thal) is considered as the most common inherited
      hemoglobin disorder worldwide. The present study describes the first observation
      of a combination of rare alpha-chain variants, and beta-globin gene cluster
      deletion. A 21-year-old woman with thalassemia trait, marked microcytosis, mild
      anemia, and normal range of Hb F was referred to Amirkola genetic center in the
      North of Iran for routine molecular test of thalassemia in the context of carrier
      detection and prevention of thalassemia major birth. Nucleotide sequencing
      revealed a novel compound heterozygosity status for two non-deletional mutations
      on HBA2, Hb O Indonesia (alpha116(GH4)Glu -> Lys), and Hb Matsue-Oki (alpha75
      (EF4) Asp -> Asn), together with heterozygosity for the sicilian (deltabeta)0
      thal mutation. This finding highlights the necessity of deep molecular
      investigation of thalassemia in regions where thalassemia is abundant, and
      present highly heterogeneous population.

PMID- 29651219
TI  - Vanillic Acid in Endometrial Carcinoma: A Role for Nitric Oxide?

PMID- 29651218
TI  - Hypocalcemia Presenting as Life Threatening Torsades de Pointes with Prolongation
      of QTc Interval.
AB  - Torsades de pointes with prolonged QTc interval is a form of ventricular
      tachycardia. Many predisposing factors have been identified and hypocalcemia is
      among the rare ones. Our case illustrates that though rare, hypocalcemia might
      manifest as torsades de pointes with prolongation of QTc interval. Early
      diagnosis and management of dyselectrolytemia can prevent these patients from
      catastrophic torsades de pointes.

PMID- 29651220
TI  - Upper Limit of Normal for Serum Alanine Transaminase in Healthy Population.

PMID- 29651221
TI  - The solvability conditions for the inverse eigenvalue problem of normal skew J
      Hamiltonian matrices.
AB  - Let [Formula: see text] be a normal matrix such that [Formula: see text], where
      [Formula: see text] is an n-by-n identity matrix. In (S. Gigola, L. Lebtahi, N.
      Thome in Appl. Math. Lett. 48:36-40, 2015) it was introduced that a matrix
      [Formula: see text] is referred to as normal J-Hamiltonian if and only if
      [Formula: see text] and [Formula: see text]. Furthermore, the necessary and
      sufficient conditions for the inverse eigenvalue problem of such matrices to be
      solvable were given. We present some alternative conditions to those given in the
      aforementioned paper for normal skew J-Hamiltonian matrices. By using Moore
      Penrose generalized inverse and generalized singular value decomposition, the
      necessary and sufficient conditions of its solvability are obtained and a
      solvable general representation is presented.

PMID- 29651222
TI  - Toward 3D Printed Hydrogen Storage Materials Made with ABS-MOF Composites.
AB  - The push to advance efficient, renewable, and clean energy sources has brought
      with it an effort to generate materials that are capable of storing hydrogen.
      Metal-organic framework materials (MOFs) have been the focus of many such studies
      as they are categorized for their large internal surface areas. We have addressed
      one of the major shortcomings of MOFs (their processibility) by creating and 3D
      printing a composite of acrylonitrile butadiene styrene (ABS) and MOF-5, a
      prototypical MOF, which is often used to benchmark H2 uptake capacity of other
      MOFs. The ABS-MOF-5 composites can be printed at MOF-5 compositions of 10% and
      below. Other physical and mechanical properties of the polymer (glass transition
      temperature, stress and strain at the breaking point, and Young's modulus) either
      remain unchanged or show some degree of hardening due to the interaction between
      the polymer and the MOF. We do observe some MOF-5 degradation through the
      blending process, likely due to the ambient humidity through the purification and
      solvent casting steps. Even with this degradation, the MOF still retains some of
      its ability to uptake H2, seen in the ability of the composite to uptake more H2
      than the pure polymer. The experiments and results described here represent a
      significant first step toward 3D printing MOF-5-based materials for H2 storage.

PMID- 29651223
TI  - The Mediating Role of Self-Criticism in the Relationship between Parental
      Expressed Emotion and NSSI.
AB  - Nonsuicidal self-injury (NSSI) is found at high rates among adolescents and young
      adults and is associated with many negative consequences, warranting additional
      research. Two factors that may contribute to NSSI during this time period are
      one's levels of self-criticism and perceptions of their parental relationships;
      however, these relationships have received limited attention. The purpose of this
      current study was to address this gap in the literature. Adolescents and young
      adults (n=294) completed measures of perceived parental expressed emotion, self
      criticism, and NSSI. Participants with a history of NSSI reported perceiving
      their parents as providing less emotional support, inducing more irritation,
      being more intrusive, and expressing more criticism compared to those without a
      history of NSSI. These individuals also endorsed greater self-criticism. Further,
      self-criticism mediated the relationship between perceived parental expressed
      emotion and NSSI occurrence, such that those with higher reported self-criticism
      and greater perceived parental expressed emotion were more likely to engage in
      NSSI.

PMID- 29651224
TI  - Racial differences in Transitions to Marriage for Unmarried Mothers.
AB  - Unlike prior studies that have explained racial differences in the transitions to
      marriage among unmarried women, our study used the Fragile Families and Child
      Wellbeing Study to examine racial differences in the transitions to marriage
      among unmarried women following a non-marital birth. We found that Black mothers
      were 60-65% more likely to delay marriage after a non-marital birth compared to
      White mothers and these racial gaps were only partially explained by economic,
      demographic and attitudinal factors. Our paper further contributes to this
      literature by examining changes in cohabitation patterns, educational attainment,
      poverty status and attitudes of gender distrust that are able to partially
      explain and reduce these racial gaps in transitions to marriage. With the general
      decline in marriage and rise in cohabitation, our paper tried to assess whether
      cohabitation is a leading factor for marriage or a substitute for marriage for
      unmarried mothers. Racial disparities have important implications for child
      wellbeing and intergenerational transmission of inequalities.

PMID- 29651225
TI  - The relationship between the spatial scaling of biodiversity and ecosystem
      stability.
AB  - Aim: Ecosystem stability and its link with biodiversity have mainly been studied
      at the local scale. Here we present a simple theoretical model to address the
      joint dependence of diversity and stability on spatial scale, from local to
      continental. Methods: The notion of stability we use is based on the temporal
      variability of an ecosystem-level property, such as primary productivity. In this
      way, our model integrates the well-known species-area relationship (SAR) with a
      recent proposal to quantify the spatial scaling of stability, called the
      invariability-area relationship (IAR). Results: We show that the link between the
      two relationships strongly depends on whether the temporal fluctuations of the
      ecosystem property of interest are more correlated within than between species.
      If fluctuations are correlated within species but not between them, then the IAR
      is strongly constrained by the SAR. If instead individual fluctuations are only
      correlated by spatial proximity, then the IAR is unrelated to the SAR. We apply
      these two correlation assumptions to explore the effects of species loss and
      habitat destruction on stability, and find a rich variety of multi-scale spatial
      dependencies, with marked differences between the two assumptions. Main
      conclusions: The dependence of ecosystem stability on biodiversity across spatial
      scales is governed by the spatial decay of correlations within and between
      species. Our work provides a point of reference for mechanistic models and data
      analyses. More generally, it illustrates the relevance of macroecology for
      ecosystem functioning and stability.

PMID- 29651226
TI  - DNA methylation affects metastasis of renal cancer and is associated with TGF
      beta/RUNX3 inhibition.
AB  - Background: Renal cell carcinoma accounts for 2-3% of all cancers and metastasis
      increased the malignancy of renal cancer. However, the role of methylation in
      metastasis of renal cancer is poorly understood. Methods: We performed targeted
      gene array to compare the differential expressions of methylation regulated genes
      in metastatic and primary renal cancer tissues. Quantitative methylation specific
      PCR was performed to examine the CpG methylation levels of Runt related
      transcription factor 3 (RUNX3) and transforming growth factor (TGF)-beta. Western
      blot was performed to detect the expression of target genes. Murine xenograft
      renal cancer model was established to assay gene expression, methylation level,
      tumor growth and animal survival in vivo. Results: RUNX3 and TGF-beta levels were
      decreased in metastatic renal cancer tissues as a result of their CpG
      methylation. Metastatic xenograft model displayed decreased expression levels of
      RUNX3 and TGF-beta and higher CpG methylation levels, bigger tumor size and
      shorter survival time, all which were restored by treatment with a methylation
      inhibitor. Conclusions: Hypermethylation in CpG islands promotes metastasis of
      renal cancer and is associated with TGF-beta and RUNX3 inhibition.

PMID- 29651228
TI  - Predicting the Kinetics of Ice Recrystallization in Aqueous Sugar Solutions.
AB  - The quality of stored frozen products such as foods and biomaterials generally
      degrades in time due to the growth of large ice crystals by recrystallization.
      While there is ample experimental evidence that recrystallization within such
      products (or model systems thereof) is often dominated by diffusion-limited
      Ostwald ripening, the application of Ostwald-ripening theories to predict
      measured recrystallization rates has only met with limited success. For a model
      system of polycrystalline ice within an aqueous solution of sugars, we here show
      recrystallization rates can be predicted on the basis of Ostwald ripening theory,
      provided (1) the theory accounts for the fact the solution can be nonideal,
      nondilute and of different density than the crystals, (2) the effect of ice-phase
      volume fraction on the diffusional flux of water between crystals is accurately
      described, and (3) all relevant material properties (involving binary Fick
      diffusion coefficients, the thermodynamic factor of the solution, and the surface
      energy of ice) are carefully estimated. To enable calculation of material
      properties, we derive an alternative formulation of Ostwald ripening in terms of
      the Maxwell-Stefan instead of the Fick approach to diffusion. First, this leads
      to a cancellation of the thermodynamic factor (a measure for the nonideality of a
      solution), which is a notoriously difficult property to obtain. Second, we show
      that Maxwell-Stefan diffusion coefficients can to a reasonable approximation be
      related to self-diffusion coefficients, which are relatively easy to measure or
      predict in comparison to Fick diffusion coefficients. Our approach is validated
      for a binary system of water and sucrose, for which we show predicted
      recrystallization rates of ice compare well to experimental results, with
      relative deviations of at most a factor of 2.

PMID- 29651227
TI  - A case of atopic dermatitis caused by Ascaris lumbricoides infection.
AB  - Background: Parasite infections stimulate total and specific IgE production that,
      in the case of Toxocara canis infection, corresponds to chronic allergic
      symptoms. There may also be other infections which have similar symptoms, such as
      Ascaris lumbricoides infection. Ascaris lumbricoides is a large nematode that
      causes abdominal pain, nausea, vomiting, bloating, anorexia and intermittent
      diarrhoea. Patients with ascaridiasis and high IgE levels may also have allergy
      like symptoms such as asthma, urticaria and atopic dermatitis. Case presentation:
      We report a case of atopic dermatitis caused by Ascaris lumbricoides which shows
      the important role of parasitic infection in patients with long-lasting
      dermatitis. The patient was a 12-year old female suffering since early infancy
      from atopic dermatitis and asthma. She was treated for dermatitis with oral
      bethametasone and topical pimecrolimus with little benefit. After two cycles of
      mebendazole therapy, the patient showed progressive improvement of symptoms.
      Conclusions: In patients with dermatitis, Ascaris lumbricoides infection should
      be not excluded: adequate anthelmintic treatment may result in complete
      regression from the disease.

PMID- 29651229
TI  - Polycatenated 2D Hydrogen-Bonded Binary Supramolecular Organic Frameworks (SOFs)
      with Enhanced Gas Adsorption and Selectivity.
AB  - Controlled assembly of two-dimensional (2D) supramolecular organic frameworks
      (SOFs) has been demonstrated through a binary strategy in which 1,4-bis-(4-(3,5
      dicyano-2,6-dipyridyl)pyridyl)naphthalene (2), generated in situ by oxidative
      dehydrogenation of 1,4-bis-(4-(3,5-dicyano-2,6
      dipyridyl)dihydropyridyl)naphthalene (1), is coupled in a 1:1 ratio with
      terphenyl-3,3',4,4'-tetracarboxylic acid (3; to form SOF-8), 5,5'-(anthracene
      9,10-diyl)diisophthalic acid (4; to form SOF-9), or 5,5'-bis-(azanediyl)-oxalyl
      diisophthalic acid (5; to form SOF-10). Complementary O-H...N hydrogen bonds
      assemble 2D 63-hcb (honeycomb) subunits that pack as layers in SOF-8 to give a
      three-dimensional (3D) supramolecular network with parallel channels hosting
      guest DMF (DMF = N,N'-dimethylformamide) molecules. SOF-9 and SOF-10 feature
      supramolecular networks of 2D -> 3D inclined polycatenation of similar hcb layers
      as those in SOF-8. Although SOF-8 suffers framework collapse upon guest removal,
      the polycatenated frameworks of SOF-9 and SOF-10 exhibit excellent chemical and
      thermal stability, solvent/moisture durability, and permanent porosity. Moreover,
      their corresponding desolvated (activated) samples SOF-9a and SOF-10a display
      enhanced adsorption and selectivity for CO2 over N2 and CH4. The structures of
      these activated compounds are well described by quantum chemistry calculations,
      which have allowed us to determine their mechanical properties, as well as
      identify their soft deformation modes and a large number of low-energy vibration
      modes. These results not only demonstrate an effective synthetic platform for
      porous organic molecular materials stabilized solely by primary hydrogen bonds
      but also suggest a viable means to build robust SOF materials with enhanced gas
      uptake capacity and selectivity.

PMID- 29651230
TI  - Sex and age differences in risk factors of marijuana involvement during
      adolescence.
AB  - Objectives: We aimed to examine whether there are sex and age differences in
      psychosocial risk factors of marijuana use during adolescence. Methods: Data were
      drawn from 57,767 adolescents (8th and 10th graders) from the 2012-2013
      Monitoring the Future study. We examined the association between socio
      demographic and behavioral correlates with different frequencies of past-year
      marijuana use (non-use, occasional use: <10 time, frequent use: 10-39 times, and
      regular use: 40+ times). We further investigated whether these associations were
      similar for boys and girls of different ages. Results: Overall, 20.6% of the
      adolescents reported past-year marijuana use: 12.1% occasional use, 4.3% frequent
      use, and 3.8% regular use. Girls were less likely to be frequent and regular
      marijuana users (frequent use: OR=0.83 [0.75, 0.93]; regular use: OR=0.41 [0.36,
      0.48]) while no sex difference was noted for occasional use. Also, the odds of
      deviant behaviors were higher as the frequencies of marijuana use were higher.
      Compared to younger girls, older boys and girls had higher association between
      all levels of marijuana use and low self-esteem, low perceived harm, peer
      influence and perceived easy access. Besides, younger boys were more likely than
      younger girls to report an association between regular marijuana use with low
      self-esteem, peer influence, and perceived easy access but not with perceived low
      harm. Conclusions/Importance: Findings suggest the relationship between these
      psychosocial correlates and frequency of marijuana involvement varies across sex
      and age groups. These variations ask for a nuanced approach to prevention of
      marijuana involvement in different groups of youth.

PMID- 29651231
TI  - Procyanidins: a comprehensive review encompassing structure elucidation via mass
      spectrometry.
AB  - Procyanidins are polyphenols abundant in dietary fruits, vegetables, nuts,
      legumes, and grains with a variety of chemopreventive biological effects. Rapid
      structure determination of these compounds is needed, notably for the more
      complex polymeric procyanidins. We review the recent developments in the
      structure elucidation of procyanidins with a focus on mass spectrometric
      approaches, especially liquid chromatography-tandem mass spectrometry (LC-MS/MS)
      and matrix-assisted laser desorption ionization (MALDI) MS/MS.

PMID- 29651232
TI  - Tal1, Gata2a, and Gata3 Have Distinct Functions in the Development of V2b and
      Cerebrospinal Fluid-Contacting KA Spinal Neurons.
AB  - Vertebrate locomotor circuitry contains distinct classes of ventral spinal cord
      neurons which each have particular functional properties. While we know some of
      the genes expressed by each of these cell types, we do not yet know how several
      of these neurons are specified. Here, we investigate the functions of Tal1,
      Gata2a, and Gata3 transcription factors in the development of two of these
      populations of neurons with important roles in locomotor circuitry: V2b neurons
      and cerebrospinal fluid-contacting Kolmer-Agduhr (KA) neurons (also called CSF
      cNs). Our data provide the first demonstration, in any vertebrate, that Tal1 and
      Gata3 are required for correct development of KA and V2b neurons, respectively.
      We also uncover differences in the genetic regulation of V2b cell development in
      zebrafish compared to mouse. In addition, we demonstrate that Sox1a and Sox1b are
      expressed by KA and V2b neurons in zebrafish, which differs from mouse, where
      Sox1 is expressed by V2c neurons. KA neurons can be divided into ventral KA"
      neurons and more dorsal KA' neurons. Consistent with previous morpholino
      experiments, our mutant data suggest that Tal1 and Gata3 are required in KA' but
      not KA" cells, whereas Gata2a is required in KA" but not KA' cells, even though
      both of these cell types co-express all three of these transcription factors. In
      gata2a mutants, cells in the KA" region of the spinal cord lose expression of
      most KA" genes and there is an increase in the number of cells expressing V3
      genes, suggesting that Gata2a is required to specify KA" and repress V3 fates in
      cells that normally develop into KA" neurons. On the other hand, our data suggest
      that Gata3 and Tal1 are both required for KA' neurons to differentiate from
      progenitor cells. In the KA' region of these mutants, cells no longer express KA'
      markers and there is an increase in the number of mitotically-active cells.
      Finally, our data demonstrate that all three of these transcription factors are
      required for later stages of V2b neuron differentiation and that Gata2a and Tal1
      have different functions in V2b development in zebrafish than in mouse.

PMID- 29651233
TI  - Near- and Far-Surround Suppression in Human Motion Discrimination.
AB  - The spatial context has strong effects on visual processing. Psychophysics and
      modeling studies have provided evidence that the surround context can
      systematically modulate the perception of center stimuli. For motion direction,
      these center-surround interactions are considered to come from spatio-directional
      interactions between direction of motion tuned neurons, which are attributed to
      the middle temporal (MT) area. Here, we investigated through psychophysics
      experiments on human subjects changes with spatial separation in center-surround
      inhibition and motion direction interactions. Center-surround motion repulsion
      effects were measured under near-and far-surround conditions. Using a simple
      physiological model of the repulsion effect we extracted theoretical population
      parameters of surround inhibition strength and tuning widths with spatial
      distance. All 11 subjects showed clear motion repulsion effects under the near
      surround condition, while only 10 subjects showed clear motion repulsion effects
      under the far-surround condition. The model predicted human performance well.
      Surround inhibition under the near-surround condition was significantly stronger
      than that under the far-surround condition, and the tuning widths were smaller
      under the near-surround condition. These results demonstrate that spatial
      separation can both modulate the surround inhibition strength and surround to
      center tuning width.

PMID- 29651234
TI  - Pathophysiology of Long Non-coding RNAs in Ischemic Stroke.
AB  - Stroke is a neurological disease with high disability and fatality rates, and
      ischemic stroke accounts for 75% of all stroke cases. The underlying
      pathophysiologic processes of ischemic stroke include oxidative stress, toxicity
      of excitatory amino acids, excess calcium ions, increased apoptosis and
      inflammation. Long non-coding RNAs (lncRNAs) may participate in the regulation of
      the pathophysiologic processes of ischemic stroke as indicated by altered
      expression of lncRNAs in blood samples of acute ischemic stroke patients, animal
      models of focal cerebral ischemia and oxygen-glucose deprivation (OGD) cell
      models. Because of the potentially important role, lncRNAs might be useful as
      biomarkers for the diagnosis, treatment and prognosis of ischemic stroke. This
      article reviews the functions of lncRNAs in different pathophysiology events of
      ischemic stroke with a focus on specific lncRNAs that may underlie ischemic
      stroke pathophysiology and that could therefore serve as potential diagnostic
      biomarkers and therapeutic targets.

PMID- 29651235
TI  - Selective Labeling of Individual Neurons in Dense Cultured Networks With
      Nanoparticle-Enhanced Photoporation.
AB  - Neurodevelopmental and neurodegenerative disorders are characterized by subtle
      alterations in synaptic connections and perturbed neuronal network functionality.
      A hallmark of neuronal connectivity is the presence of dendritic spines, micron
      sized protrusions of the dendritic shaft that compartmentalize single synapses to
      fine-tune synaptic strength. However, accurate quantification of spine density
      and morphology in mature neuronal networks is hampered by the lack of targeted
      labeling strategies. To resolve this, we have optimized a method to deliver cell
      impermeable compounds into selected cells based on Spatially resolved
      NAnoparticle-enhanced Photoporation (SNAP). We show that SNAP enables efficient
      labeling of selected individual neurons and their spines in dense cultured
      networks without affecting short-term viability. We compare SNAP with widely used
      spine labeling techniques such as the application of lipophilic dyes and
      genetically encoded fluorescent markers. Using SNAP, we demonstrate a time
      dependent increase in spine density in healthy cultures as well as a reduction in
      spine density after chemical mimicry of hypoxia. Since the sparse labeling
      procedure can be automated using an intelligent acquisition scheme, SNAP holds
      promise for high-content screening campaigns of neuronal connectivity in the
      context of neurodevelopmental and neurodegenerative disorders.

PMID- 29651237
TI  - DPP6 Loss Impacts Hippocampal Synaptic Development and Induces Behavioral
      Impairments in Recognition, Learning and Memory.
AB  - DPP6 is well known as an auxiliary subunit of Kv4-containing, A-type K+ channels
      which regulate dendritic excitability in hippocampal CA1 pyramidal neurons. We
      have recently reported, however, a novel role for DPP6 in regulating dendritic
      filopodia formation and stability, affecting synaptic development and function.
      These results are notable considering recent clinical findings associating DPP6
      with neurodevelopmental and intellectual disorders. Here we assessed the
      behavioral consequences of DPP6 loss. We found that DPP6 knockout (DPP6-KO) mice
      are impaired in hippocampus-dependent learning and memory. Results from the
      Morris water maze and T-maze tasks showed that DPP6-KO mice exhibit slower
      learning and reduced memory performance. DPP6 mouse brain weight is reduced
      throughout development compared with WT, and in vitro imaging results indicated
      that DPP6 loss affects synaptic structure and motility. Taken together, these
      results show impaired synaptic development along with spatial learning and memory
      deficiencies in DPP6-KO mice.

PMID- 29651239
TI  - Editorial: Spontaneous Activity in Sensory Systems.

PMID- 29651238
TI  - PAR-Complex and Crumbs Function During Photoreceptor Morphogenesis and Retinal
      Degeneration.
AB  - The fly photoreceptor has long been used as a model to study sensory neuron
      morphogenesis and retinal degeneration. In particular, elucidating how these
      cells are built continues to help further our understanding of the mechanisms of
      polarized cell morphogenesis, intracellular trafficking and the causes of human
      retinal pathologies. The conserved PAR complex, which in flies consists of Cdc42
      PAR6-aPKC-Bazooka, and the transmembrane protein Crumbs (Crb) are key players
      during photoreceptor morphogenesis. While the PAR complex regulates polarity in
      many cell types, Crb function in polarity is relatively specific to epithelial
      cells. Together Cdc42-PAR6-aPKC-Bazooka and Crb orchestrate the differentiation
      of the photoreceptor apical membrane (AM) and zonula adherens (ZA), thus allowing
      these cells to assemble into a neuro-epithelial lattice. In addition to its
      function in epithelial polarity, Crb has also been shown to protect fly
      photoreceptors from light-induced degeneration, a process linked to Rhodopsin
      expression and trafficking. Remarkably, mutations in the human Crumbs1 (CRB1)
      gene lead to retinal degeneration, making the fly photoreceptor a powerful
      disease model system.

PMID- 29651236
TI  - Substrates for Neuronal Cotransmission With Neuropeptides and Small Molecule
      Neurotransmitters in Drosophila.
AB  - It has been known for more than 40 years that individual neurons can produce more
      than one neurotransmitter and that neuropeptides often are colocalized with small
      molecule neurotransmitters (SMNs). Over the years much progress has been made in
      understanding the functional consequences of cotransmission in the nervous system
      of mammals. There are also some excellent invertebrate models that have revealed
      roles of coexpressed neuropeptides and SMNs in increasing complexity,
      flexibility, and dynamics in neuronal signaling. However, for the fly Drosophila
      there are surprisingly few functional studies on cotransmission, although there
      is ample evidence for colocalization of neuroactive compounds in neurons of the
      CNS, based both on traditional techniques and novel single cell transcriptome
      analysis. With the hope to trigger interest in initiating cotransmission studies,
      this review summarizes what is known about Drosophila neurons and neuronal
      circuits where different neuropeptides and SMNs are colocalized. Coexistence of
      neuroactive substances has been recorded in different neuron types such as
      neuroendocrine cells, interneurons, sensory cells and motor neurons. Some of the
      circuits highlighted here are well established in the analysis of learning and
      memory, circadian clock networks regulating rhythmic activity and sleep, as well
      as neurons and neuroendocrine cells regulating olfaction, nociception, feeding,
      metabolic homeostasis, diuretic functions, reproduction, and developmental
      processes. One emerging trait is the broad role of short neuropeptide F in
      cotransmission and presynaptic facilitation in a number of different neuronal
      circuits. This review also discusses the functional relevance of coexisting
      peptides in the intestine. Based on recent single cell transcriptomics data, it
      is likely that the neuronal systems discussed in this review are just a fraction
      of the total set of circuits where cotransmission occurs in Drosophila. Thus, a
      systematic search for colocalized neuroactive compounds in further neurons in
      anatomically defined circuits is of interest for the near future.

PMID- 29651241
TI  - Intra- and Inter-Regional Priming of Ipsilateral Human Primary Motor Cortex With
      Continuous Theta Burst Stimulation Does Not Induce Consistent Neuroplastic
      Effects.
AB  - Human responses to non-invasive brain stimulation (NIBS) techniques can be highly
      variable. Recently, priming protocols involving a conditioning round of NIBS
      applied to a target brain region prior to the application of a test protocol have
      shown promise in inducing more reliable effects. We investigated whether intra-
      or inter-regional priming of the left primary motor cortex (M1) using continuous
      theta burst stimulation (cTBS) can induce consistent, and reliable modulation of
      corticospinal excitability. Twenty healthy adults (six males) underwent four cTBS
      protocols. For intra-regional priming, cTBS was applied twice to the left M1 (M1
      M1). For inter-regional M1 priming, cTBS was applied to the ipsilateral (left)
      dorsal premotor cortex (dPMC-M1), and ipsilateral (left) dorsolateral prefrontal
      cortex (DLPFC-M1). In the control condition, sham stimulation was applied to left
      M1, followed by active cTBS also applied to the left M1 (sham-M1). Each round of
      cTBS was separated by 10 min. Neuroplastic responses were indexed using motor
      evoked potentials (MEPs) elicited from the left M1 hand region, and measured from
      the contralateral first dorsal interosseous (right hand). MEP measurements were
      taken before the first round of cTBS priming, then immediately, 10, 20 and 30 min
      after the second test round of cTBS. The primary two-way repeated measures ANOVA
      revealed no significant differences in MEP responses across each condition (no
      main effects or interaction). Intra- and inter-regional priming of the left M1
      using cTBS does not induce consistent neuroplastic effects. Further work is
      required to identify factors which contribute to such variability in human
      responses to NIBS.

PMID- 29651240
TI  - Cognitive Neuroscience of Attention Deficit Hyperactivity Disorder (ADHD) and Its
      Clinical Translation.
AB  - This review focuses on the cognitive neuroscience of Attention Deficit
      Hyperactivity Disorder (ADHD) based on functional magnetic resonance imaging
      (fMRI) studies and on recent clinically relevant applications such as fMRI-based
      diagnostic classification or neuromodulation therapies targeting fMRI deficits
      with neurofeedback (NF) or brain stimulation. Meta-analyses of fMRI studies of
      executive functions (EFs) show that ADHD patients have cognitive-domain
      dissociated complex multisystem impairments in several right and left hemispheric
      dorsal, ventral and medial fronto-cingulo-striato-thalamic and fronto-parieto
      cerebellar networks that mediate cognitive control, attention, timing and working
      memory (WM). There is furthermore emerging evidence for abnormalities in orbital
      and ventromedial prefrontal and limbic areas that mediate motivation and emotion
      control. In addition, poor deactivation of the default mode network (DMN)
      suggests an abnormal interrelationship between hypo-engaged task-positive and
      poorly "switched off" hyper-engaged task-negative networks, both of which are
      related to impaired cognition. Translational cognitive neuroscience in ADHD is
      still in its infancy. Pattern recognition analyses have attempted to provide
      diagnostic classification of ADHD using fMRI data with respectable classification
      accuracies of over 80%. Necessary replication studies, however, are still
      outstanding. Brain stimulation has been tested in heterogeneously designed, small
      numbered proof of concept studies targeting key frontal functional impairments in
      ADHD. Transcranial direct current stimulation (tDCS) appears to be promising to
      improve ADHD symptoms and cognitive functions based on some studies, but larger
      clinical trials of repeated stimulation with and without cognitive training are
      needed to test clinical efficacy and potential costs on non-targeted functions.
      Only three studies have piloted NF of fMRI-based frontal dysfunctions in ADHD
      using fMRI or near-infrared spectroscopy, with the two larger ones finding some
      improvements in cognition and symptoms, which, however, were not superior to the
      active control conditions, suggesting potential placebo effects.
      Neurotherapeutics seems attractive for ADHD due to their safety and potential
      longer-term neuroplastic effects, which drugs cannot offer. However, they need to
      be thoroughly tested for short- and longer-term clinical and cognitive efficacy
      and their potential for individualized treatment.

PMID- 29651242
TI  - Discovery of Novel Inhibitors of Indoleamine 2,3-Dioxygenase 1 Through Structure
      Based Virtual Screening.
AB  - Indoleamine 2,3-dioxygenase 1 (IDO1) is an intracellular monomeric heme
      containing enzyme that catalyzes the first and the rate limiting step in
      catabolism of tryptophan via the kynurenine (KYN) pathway, which plays a
      significant role in the proliferation and differentiation of T cells. IDO1 has
      been proven to be an attractive target for anticancer therapy and chronic viral
      infections. In the present study, a class of IDO1 inhibitors with novel scaffolds
      were identified by virtual screening and biochemical validation, in which the
      compound DC-I028 shows moderate IDO1 inhibitory activity with an IC50 of 21.61
      MUM on enzymatic level and 89.11 MUM on HeLa cell. In the following hit expansion
      stage, DC-I02806, an analog of DC-I028, showed better inhibitory activity with
      IC50 about 18 MUM on both enzymatic level and cellular level. The structure
      activity relationship (SAR) of DC-I028 and its analogs was then discussed based
      on the molecular docking result. The novel IDO1 inhibitors of DC-I028 and its
      analogs may provide useful clues for IDO1 inhibitor development.

PMID- 29651244
TI  - Ethical Challenges for an Understanding of Suffering: Voluntary Stopping of
      Eating and Drinking and the Wish to Hasten Death in Advanced Patients.
AB  - Some persons with advanced disease but no significant cognitive impairments
      consciously decide to stop taking food and fluids orally, even though they remain
      physically able to do so. The question is to what extent voluntarily stopping
      eating and drinking (VSED) may be considered an expression of a wish to hasten
      death, in the sense that the latter has been defined recently. We analyze the
      data reported in some studies in relation to primary care patients who died as a
      result of VSED and examine their results in light of the qualitative findings of
      patients that expressed a wish to die. In our view, VSED can be understood as a
      response to physical/psychological/spiritual suffering, as an expression of a
      loss of self, a desire to live but not in this way, a way of ending suffering,
      and as a kind of control over one's life. Thus, VSED is consistent with the wish
      to hasten death. Prior to interpreting this act as a deliberate expression of
      personal autonomy, it is important to explore all possible areas of suffering,
      including physical symptoms, psychological distress, existential suffering, and
      social aspects. Failure to do so will mean that we run the risk of abandoning a
      fellow human being to his or her suffering.

PMID- 29651243
TI  - PR Toxin - Biosynthesis, Genetic Regulation, Toxicological Potential, Prevention
      and Control Measures: Overview and Challenges.
AB  - Out of the various mycotoxigenic food and feed contaminant, the fungal species
      belonging to Penicillium genera, particularly Penicillium roqueforti is of great
      economic importance, and well known for its crucial role in the manufacturing of
      Roquefort and Gorgonzola cheese. The mycotoxicosis effect of this mold is due to
      secretion of several metabolites, of which PR toxin is of considerable
      importance, with regard to food quality and safety challenges issues. The food
      products and silages enriched with PR toxin could lead into damage to vital
      internal organs, gastrointestinal perturbations, carcinogenicity, immunotoxicity,
      necrosis, and enzyme inhibition. Moreover, it also has the significant mutagenic
      potential to disrupt/alter the crucial processes like DNA replication,
      transcription, and translation at the molecular level. The high genetic
      diversities in between the various strains of P. roqueforti persuaded their
      nominations with Protected Geographical Indication (PGI), accordingly to the
      cheese type, they have been employed. Recently, the biosynthetic mechanism and
      toxicogenetic studies unraveled the role of ari1 and prx gene clusters that cross
      talk with the synthesis of other metabolites or involve other cross-regulatory
      pathways to negatively regulate/inhibit the other biosynthetic route targeted for
      production of a strain-specific metabolites. Interestingly, the chemical
      conversion that imparts toxic properties to PR toxin is the
      substitution/oxidation of functional hydroxyl group (-OH) to aldehyde group (
      CHO). The rapid conversion of PR toxin to the other derivatives such as PR imine,
      PR amide, and PR acid, based on conditions available reflects their unstability
      and degradative aspects. Since the PR toxin-induced toxicity could not be
      eliminated safely, the assessment of dose-response and other pharmacological
      aspects for its safe consumption is indispensable. The present review describes
      the natural occurrences, diversity, biosynthesis, genetics, toxicological
      aspects, control and prevention strategies, and other management aspects of PR
      toxin with paying special attention on economic impacts with intended
      legislations for avoiding PR toxin contamination with respect to food security
      and other biosafety purposes.

PMID- 29651245
TI  - Antiseptic Activity of Ethnomedicinal Xuebijing Revealed by the Metabolomics
      Analysis Using UHPLC-Q-Orbitrap HRMS.
AB  - Xuebijing (XBJ) injection is an ethnomedicinal formula that has been widely used
      in the therapy of sepsis in China. However, the underlying theraputic mechanisms
      remain uninvestigated. In this research, a metabolomic method based on UHPLC-Q
      Orbitrap HRMS was applied to make a holistic evaluation of XBJ on septic rats
      which were induced by the classical cecal ligation and puncture (CLP) operation.
      The plasma metabolic changes were profiled and evaluated by multivariate
      analytical (MVA) methods. In the results, a total of 41 differential metabolites
      were identified between CLP-operated group and sham-operated group, which were
      mainly involved in amino acid metabolism and lipid metabolism. After pathway
      analysis, it was finally discovered that the majority of the influenced metabolic
      pathways caused by sepsis mainly involved in energy metabolism, oxidative stress,
      and inflammation metabolism. When intervened by XBJ injection, 32 of the 41
      disordered metabolites had been adjusted in reverse, which suggested that XBJ
      could mediate the abnormal metabolic pathways synergistically. In conclusion, the
      present study systematically investigated the efficacy and its underlying
      therapeutic mechanisms of XBJ on sepsis, while offering a new insight for the
      subsequent relevant exploration of other Chinese medicine at the same time.

PMID- 29651246
TI  - Lactone Component From Ligusticum chuanxiong Alleviates Myocardial Ischemia
      Injury Through Inhibiting Autophagy.
AB  - The dysregulation of autophagy is associated with a series of cardiovascular
      diseases, such as myocardial ischemia injury. Lactone component from Ligusticum
      chuanxiong (LLC) is the major constituent of the traditional Chinese herb L.
      chuanxiong Hort., which has been reported to hold potential cardioprotective
      effects. In this study, to determine whether LLC protects the heart through
      regulation of autophagy, we explored the effects of LLC on cardioprotection and
      autophagy in myocardial ischemia injured rats and H9c2 cardiomyocytes. Our
      results showed that LLC significantly reduced infarct size and serum levels of
      lactate dehydrogenase, creatine kinase, and cardiac troponin and ameliorated
      histological features in a dose-dependent manner. Similar protections were
      observed in cardiomyocytes subjected to oxygen-glucose deprivation (OGD).
      Meanwhile, LLC inhibited autophagy induced by myocardial ischemia injury,
      characterized by increased autophagic vacuoles, LC3-II/LC3-I ratio and the
      expression of Beclin 1, whereas decreased the expression of p62. Additionally,
      LLC combined with a lysosomal inhibitor chloroquine (CQ) reduced LC3-II/LC3-I
      ratio in cardiomyocytes compared with CQ alone. Furthermore, LLC-afforded
      cardioprotection was abolished by a specific PI3K inhibitor LY294002.
      Collectively, these findings demonstrated that cardioprotective effects of LLC
      were related to restoration of autophagic flux through the activation of
      PI3K/Akt/mTOR signaling pathway.

PMID- 29651247
TI  - Application of the Athlete's Performance Passport for Doping Control: A Case
      Report.
AB  - The efficient use of testing resources is a key issue in the fight against
      doping. The longitudinal tracking of sporting performances to identify unusual
      improvements possibly caused by doping, so-called "athlete's performance
      passport" (APP) is a new concept to improve targeted anti-doping testing. In
      fact, unusual performances by an athlete would trigger a more thorough testing
      program. In the present case report, performance data is modeled using the
      critical power concept for a group of athletes based on their past performances.
      By these means, an athlete with unusual deviations from his predicted
      performances was identified. Subsequent target testing using blood testing and
      the athlete biological passport resulted in an anti-doping rule violation
      procedure and suspension of the athlete. This case demonstrates the feasibility
      of the APP approach where athlete's performance is monitored and might serve as
      an example for the practical implementation of the method.

PMID- 29651249
TI  - Ontogenetic and Experience-Dependent Changes in Defensive Behavior in Captive
      Bred Hawaiian Bobtail Squid, Euprymna scolopes.
AB  - Cephalopod molluscs are known for their extensive behavioral repertoire and their
      impressive learning abilities. Their primary defensive behaviors, such as
      camouflage, have received detailed study, but knowledge is limited to intensive
      study of relatively few species. A considerable challenge facing cephalopod
      research is the need to establish new models that can be captive bred, are
      tractable for range of different experimental procedures, and that will address
      broad questions in biological research. The Hawaiian Bobtail Squid (Euprymna
      scolopes) is a small, tropical cephalopod that has a long history of research in
      the field of microbial symbiosis, but offers great promise as a novel behavioral
      and neurobiological model. It can be bred in the laboratory through multiple
      generations, one of the few species of cephalopod that can meet this requirement
      (which is incorporated in regulations such as EU directive 2010/63/EU).
      Additionally, laboratory culture makes E. scolopes an ideal model for studying
      ontogeny- and experience-dependent behaviors. In this study, we show that captive
      bred juvenile and adult E. scolopes produce robust, repeatable defensive
      behaviors when placed in an exposed environment and presented with a visual
      threat. Further, adult and juvenile squid employ different innate defensive
      behaviors when presented with a size-matched model predator. When a 10-min
      training procedure was repeated over three consecutive days, defensive behaviors
      habituated in juvenile squid for at least 5 days after training, but memory did
      not appear to persist for 14 days. In contrast, adult squid did not show any
      evidence of long-term habituation memory. Thus we conclude that this species
      produces a range of quantifiable, modifiable behaviors even in a laboratory
      environment where ecologically-relevant, complex behavioral sequences may not
      reliably occur. We suggest that the lack of long-term memory in adult squid may
      be related to their less escalated initial response to the mimic, and thus
      indicates less motivation to retain memory and not necessary inability to form
      memory. This is the first demonstration of age-related differences in defensive
      behaviors in Euprymna, and the first record of habituation in this experimentally
      tractable genus of squid.

PMID- 29651248
TI  - Carbon Nanotubes and Other Engineered Nanoparticles Induced Pathophysiology on
      Mesothelial Cells and Mesothelial Membranes.
AB  - Nanoparticles have great potential for numerous applications due to their unique
      physicochemical properties. However, concerns have been raised that they may
      induce deleterious effects on biological systems. There is accumulating evidence
      that, like asbestos, inhaled nanomaterials of >5 MUm and high aspect ratio (3:1),
      particularly rod-like carbon nanotubes, may inflict pleural disease including
      mesothelioma. Additionally, a recent set of case reports suggests that inhalation
      of polyacrylate/nanosilica could in part be associated with inflammation and
      fibrosis of the pleura of factory workers. However, the adverse outcomes of
      nanoparticle exposure to mesothelial tissues are still largely unexplored. In
      that context, the present review aims to provide an overview of the relevant
      pathophysiological implications involving toxicological studies describing
      effects of engineered nanoparticles on mesothelial cells and membranes. In vitro
      studies primarily emphasize on simulating cellular uptake and toxicity of
      nanotubes on benign or malignant cell lines. On the other hand, in vivo studies
      focus on illustrating endpoints of serosal pathology in rodent animal models.
      From a molecular aspect, some nanoparticle categories are shown to be cytotoxic
      and genotoxic after acute treatment, whereas chronic incubation may lead to
      malignant-like transformation. At an organism level, a number of fibrous shaped
      nanotubes are related with features of chronic inflammation and MWCNT-7 is the
      only type to consistently inflict mesothelioma.

PMID- 29651250
TI  - Efficacy of Stochastic Vestibular Stimulation to Improve Locomotor Performance
      During Adaptation to Visuomotor and Somatosensory Distortion.
AB  - Astronauts exposed to microgravity face sensorimotor challenges affecting balance
      control when readapting to Earth's gravity upon return from spaceflight. Small
      amounts of electrical noise applied to the vestibular system have been shown to
      improve balance control during standing and walking under discordant sensory
      conditions in healthy subjects, likely by enhancing information transfer through
      the phenomenon of stochastic resonance. The purpose of this study was to test the
      hypothesis that imperceptible levels of stochastic vestibular stimulation (SVS)
      could improve short-term adaptation to a locomotor task in a novel sensory
      discordant environment. Healthy subjects (14 males, 10 females, age = 28.7 +/-
      5.3 years, height = 167.2 +/- 9.6 cm, weight = 71.0 +/- 12.8 kg) were tested for
      perceptual thresholds to sinusoidal currents applied across the mastoids.
      Subjects were then randomly and blindly assigned to an SVS group receiving a 0-30
      Hz Gaussian white noise electrical stimulus at 50% of their perceptual threshold
      (stim) or a control group receiving zero stimulation during Functional Mobility
      Tests (FMTs), nine trials of which were done under conditions of visual
      discordance (wearing up/down vision reversing goggles). Time to complete the
      course (TCC) was used to test the effect of SVS between the two groups across the
      trials. Adaptation rates from the normalized TCCs were also compared utilizing
      exponent values of power fit trendline equations. A one-tailed independent
      samples t-test indicated these adaptation rates were significantly faster in the
      stim group (n = 12) than the control (n = 12) group [t(16.18) = 2.00, p = 0.031].
      When a secondary analysis was performed comparing "responders" (subjects who
      showed faster adaptation rates) of the stim (n = 7) group to the control group (n
      = 12), independent-samples t-tests revealed significantly faster trial times for
      the last five trials with goggles in the stim group "responders" than the
      controls. The data suggests that SVS may be capable of improving short-term
      adaptation to a locomotion task done under sensory discordance in a group of
      responsive subjects.

PMID- 29651252
TI  - Intra-session and Inter-day Reliability of the Myon 320 Electromyography System
      During Sub-maximal Contractions.
AB  - Electromyography systems are widely used within the field of scientific and
      clinical practices. The reliability of these systems are paramount when
      conducting research. The reliability of Myon 320 Surface Electromyography System
      is yet to be determined. This study aims to determine the intra-session and inter
      day reliability of the Myon 320 Surface Electromyography System. Muscle activity
      from fifteen participants was measured at the anterior deltoid muscle during a
      bilateral front raise exercise, the vastus lateralis muscle during a squat
      exercise and the extensor carpi radialis brevis (ECRB) muscle during an isometric
      handgrip task. Intra-session and inter-day reliability was calculated by
      intraclass correlation coefficient, standard error of measurement and coefficient
      of variation (CV). The normalized root mean squared (RMS) surface
      electromyographic signals produced good intra-session and inter-day testing
      intraclass correlation coefficient values (range: 0.63-0.97) together with low
      standard error of measurement (range: 1.49-2.32) and CV (range: 95% Confidence
      Interval = 0.36-12.71) measures for the dynamic-and-isometric contractions. The
      findings indicate that the Myon 320 Surface Electromyography System produces good
      to fair reliability when examining intra-session and inter-day reliability.
      Findings of the study provide evidence of the reliability of electromyography
      between trials which is essential during clinical testing.

PMID- 29651251
TI  - Induced Hyperproteinemia and Its Effects on the Remodeling of Fat Bodies in
      Silkworm, Bombyx mori.
AB  - Hyperproteinemia, which is characterized by an abnormally elevated plasma protein
      concentration (PPC), is a high-mortality, metabolic complication associated with
      severe liver and kidney disease. It is difficult to clinically distinguish the
      difference between the impacts of primary diseases and hyperproteinemia on
      tissues and organs, and there are no available animal models of hyperproteinemia.
      Here, we constructed an animal model of hyperproteinemia with a controllable PPC
      and no primary disease effects in the silkworm Bombyx mori that has attracted
      interest owing to its potential use in the pathological analysis of model
      animals. Silkworm have an open circulatory system in which each organ is directly
      immersed in hemolymph. The fat body (FB) of a silkworm, as a major organ for
      nutrient storage and energy metabolism, can effectively reflect hyperproteinemia
      induced metabolic abnormalities in damaged visceral tissues. A pathogenesis study
      showed that hyperproteinemia attenuated cell autophagy and apoptosis by
      attenuating an endocrine hormone, thereby preventing FB remodeling during
      metamorphosis. Meanwhile, hyperproteinemia increased oxidative stress in the FB
      and resulted in a dysfunction of amino acid conversion. Supplementation with
      exogenous 20-hydroxyecdysone effectively mitigated the hyperproteinemia-mediated
      inhibition of FB remodeling.

PMID- 29651253
TI  - A Lactate Kinetics Method for Assessing the Maximal Lactate Steady State
      Workload.
AB  - During a continuously increasing exercise workload (WL) a point will be reached
      at which arterial lactate accumulates rapidly. This so-called lactate threshold
      (LT) is associated with the maximal lactate steady state workload (MLSSW), the
      highest WL, at which arterial lactate concentration [LA] does not change.
      However, the physiological range in which the LT and the MLSSW occur has not been
      demonstrated directly. We used minor WL variations in the MLSSW range to assess
      arterial lactate kinetics in 278 treadmill and 148 bicycle ergometer exercise
      tests. At a certain workload, minimal further increment of running speed (0.1
      0.15 m/s) or cycling power (7-10 W) caused a steep elevation of [LA] (0.9 +/-
      0.43 mM, maximum increase 2.4 mM), indicating LT achievement. This sharp [LA]
      increase was more pronounced when higher WL increments were used (0.1 vs. 0.30
      m/s, P = 0.02; 0.15 vs. 0.30 m/s, P < 0.001; 7 vs. 15 W, P = 0.002; 10 vs. 15 W,
      P = 0.001). A subsequent workload reduction (0.1 m/s/7 W) stopped the [LA]
      increase indicating MLSSW realization. LT based determination of running speed
      (MLSSW) was highly reproducible on a day-to-day basis (r = 0.996, P < 0.001),
      valid in a 10 km constant velocity setting (r = 0.981, P < 0.001) and a half
      marathon race (r = 0.969, P < 0.001). These results demonstrate a fine-tuned
      regulation of exercise-related lactate metabolism, which can be reliably captured
      by assessing lactate kinetics at the MLSSW.

PMID- 29651254
TI  - Antioxidant Role of PcGSTd1 in Fenpropathrin Resistant Population of the Citrus
      Red Mite, Panonychus citri (McGregor).
AB  - The citrus red mite, Panonychus citri, a major citrus pest distributed worldwide,
      has evolved severe resistance to various classes of chemical
      acaricides/insecticides including pyrethroids. It is well known that the
      resistance to pyrethroids is mainly caused by point mutations of voltage-gated
      sodium channel gene in a wide range of pests. However, increasing number of
      evidences support that pyrethroids resistance might also be resulted from the
      integrated mechanisms including metabolic mechanisms. In this study, firstly,
      comparative analysis of RNA-seq data showed that multiple detoxification genes,
      including a GSTs gene PcGSTd1, were up-regulated in a fenpropathrin-resistant
      population compared with the susceptible strain (SS). Quantitative real time-PCR
      results showed that the exposure of fenpropathrin had an induction effect on the
      transcription of PcGSTd1 in a time-dependent manner. In vitro inhibition and
      metabolic assay of recombinant PcGSTd1 found that fenpropathrin might not be
      metabolized directly by this protein. However, its antioxidant role in
      alleviating the oxidative stress caused by fenpropathrin was demonstrated via the
      reversely genetic experiment. Our results provide a list of candidate genes which
      may contribute to a multiple metabolic mechanisms implicated in the evolution of
      fenpropathrin resistance in the field population of P. citri. Furthermore, during
      the detoxification process, PcGSTd1 plays an antioxidant role by detoxifying
      lipid peroxidation products induced by fenpropathrin.

PMID- 29651255
TI  - Sex-Specific Skeletal Muscle Fatigability and Decreased Mitochondrial Oxidative
      Capacity in Adult Rats Exposed to Postnatal Hyperoxia.
AB  - Premature birth affects more than 10% of live births, and is characterized by
      relative hyperoxia exposure in an immature host. Long-term consequences of
      preterm birth include decreased aerobic capacity, decreased muscular strength and
      endurance, and increased prevalence of metabolic diseases such as type 2 diabetes
      mellitus. Postnatal hyperoxia exposure in rodents is a well-established model of
      chronic lung disease of prematurity, and also recapitulates the pulmonary
      vascular, cardiovascular, and renal phenotype of premature birth. The objective
      of this study was to evaluate whether postnatal hyperoxia exposure in rats could
      recapitulate the skeletal and metabolic phenotype of premature birth, and to
      characterize the subcellular metabolic changes associated with postnatal
      hyperoxia exposure, with a secondary aim to evaluate sex differences in this
      model. Compared to control rats, male rats exposed to 14 days of postnatal
      hyperoxia then aged to 1 year demonstrated higher skeletal muscle fatigability,
      lower muscle mitochondrial oxidative capacity, more mitochondrial damage, and
      higher glycolytic enzyme expression. These differences were not present in female
      rats with the same postnatal hyperoxia exposure. This study demonstrates
      detrimental mitochondrial and muscular outcomes in the adult male rat exposed to
      postnatal hyperoxia. Given that young adults born premature also demonstrate
      skeletal muscle dysfunction, future studies are merited to determine whether this
      dysfunction as well as reduced aerobic capacity is due to reduced mitochondrial
      oxidative capacity and metabolic dysfunction.

PMID- 29651257
TI  - Mindfulness-Based Interventions for the Treatment of Substance and Behavioral
      Addictions: A Systematic Review.
AB  - Background: Emotion (dys)regulation as well as the interventions for improving
      these difficulties are receiving a growing attention in the literature. The aim
      of the present paper was to conduct a systematic review about the efficacy of
      mindfulness-based interventions (MBIs) in both substance and behavioral
      addictions (BAs). Method: A literature search was conducted using Cochrane,
      PubMed, and Web of Science. Fifty-four randomized controlled trials published in
      English since 2009 to April 2017 were included into a narrative synthesis.
      Results: Mindfulness-based interventions were applied in a wide range of
      addictions, including substance use disorders (from smoking to alcohol, among
      others) and BAs (namely, gambling disorder). These treatments were successful for
      reducing dependence, craving, and other addiction-related symptoms by also
      improving mood state and emotion dysregulation. The most commonly used MBI
      approaches were as follows: Mindfulness-Based Relapse Prevention, Mindfulness
      Training for Smokers, or Mindfulness-Oriented Recovery Enhancement, and the most
      frequent control group in the included studies was Treatment as Usual (TAU). The
      most effective approach was the combination of MBIs with TAU or other active
      treatments. However, there is a lack of studies showing the maintenance of the
      effect over time. Therefore, studies with longer follow-ups are needed.
      Conclusion: The revised literature shows support for the effectiveness of the
      MBIs. Future research should focus on longer follow-up assessments as well as on
      adolescence and young population, as they are a vulnerable population for
      developing problems associated with alcohol, drugs, or other addictions.

PMID- 29651256
TI  - Brain Structural Covariance Network Topology in Remitted Posttraumatic Stress
      Disorder.
AB  - Posttraumatic stress disorder (PTSD) is a prevalent, chronic disorder with high
      psychiatric morbidity; however, a substantial portion of affected individuals
      experience remission after onset. Alterations in brain network topology derived
      from cortical thickness correlations are associated with PTSD, but the effects of
      remitted symptoms on network topology remain essentially unexplored. In this
      cross-sectional study, US military veterans (N = 317) were partitioned into three
      diagnostic groups, current PTSD (CURR-PTSD, N = 101), remitted PTSD with lifetime
      but no current PTSD (REMIT-PTSD, N = 35), and trauma-exposed controls (CONTROL, n
      = 181). Cortical thickness was assessed for 148 cortical regions (nodes) and
      suprathreshold interregional partial correlations across subjects constituted
      connections (edges) in each group. Four centrality measures were compared with
      characterize between-group differences. The REMIT-PTSD and CONTROL groups showed
      greater centrality in left frontal pole than the CURR-PTSD group. The REMIT-PTSD
      group showed greater centrality in right subcallosal gyrus than the other two
      groups. Both REMIT-PTSD and CURR-PTSD groups showed greater centrality in right
      superior frontal sulcus than CONTROL group. The centrality in right subcallosal
      gyrus, left frontal pole, and right superior frontal sulcus may play a role in
      remission, current symptoms, and PTSD history, respectively. The network
      centrality changes in critical brain regions and structural networks are
      associated with remitted PTSD, which typically coincides with enhanced functional
      behaviors, better emotion regulation, and improved cognitive processing. These
      brain regions and associated networks may be candidates for developing novel
      therapies for PTSD. Longitudinal work is needed to characterize vulnerability to
      chronic PTSD, and resilience to unremitting PTSD.

PMID- 29651258
TI  - Associations Between Core Symptoms of Attention Deficit Hyperactivity Disorder
      and Both Binge and Restrictive Eating.
AB  - Introduction: It is unclear whether core symptoms of attention deficit
      hyperactivity disorder (ADHD) relate to specific types of disordered eating and
      little is known about the mediating mechanisms. We investigated associations
      between core symptoms of ADHD and binge/disinhibited eating and restrictive
      eating behavior and assessed whether negative mood and/or deficits in awareness
      and reliance on internal hunger/satiety cues mediate these relationships.
      Methods: In two independent studies, we used a dimensional approach to study ADHD
      and disordered eating. In Study 1, a community-based sample of 237 adults (72.6%
      female, 18-60 years [M = 26.8, SE = 0.6]) completed an online questionnaire,
      assessing eating attitudes/behaviors, negative mood, awareness, and reliance on
      internal hunger/satiety cues and ADHD symptomatology. In Study 2, 142 students
      (80.3% female, 18-32 years [M = 19.3, SE = 0.1]) were recruited to complete the
      same questionnaires and complete tasks assessing interoceptive sensitivity and
      impulsivity in the laboratory. Results: In each study, core symptoms of ADHD
      correlated positively with both binge/disinhibited and restrictive eating and
      negative mood mediated the relationships. Deficits in awareness and reliance on
      internal hunger/satiety signals also mediated the association between inattentive
      symptoms of ADHD and disordered eating, especially binge/disinhibited eating. The
      results from both studies demonstrated that inattentive symptoms of ADHD were
      also directly related to binge/disinhibited eating behavior, while accounting for
      the indirect pathways of association via negative mood and awareness and reliance
      on internal hunger/satiety signals. Conclusion: This research provides evidence
      that core symptoms of ADHD are associated with both binge/disinhibited eating and
      restrictive eating behavior. Further investigation of the role of inattentive
      symptoms of ADHD in disordered eating may be helpful in developing novel
      treatments for both ADHD and binge eating.

PMID- 29651259
TI  - Perinatal Hypoxia and Ischemia in Animal Models of Schizophrenia.
AB  - Intrauterine or perinatal complications constitute a major risk for psychiatric
      diseases. Infants who suffered from hypoxia-ischemia (HI) are at twofold risk to
      develop schizophrenia in later life. Several animal models attempt to reproduce
      these complications to study the yet unknown steps between an insult in early
      life and outbreak of the disease decades later. However, it is very challenging
      to find the right type and severity of insult leading to a disease-like phenotype
      in the animal, but not causing necrosis and focal neurological deficits. By
      contrast, too mild, repetitive insults may even be protective via conditioning
      effects. Thus, it is not surprising that animal models of hypoxia lead to mixed
      results. To achieve clinically translatable findings, better protocols are
      urgently needed. Therefore, we compare widely used models of hypoxia and HI and
      propose future directions for the field.

PMID- 29651260
TI  - Number of Meanings and Number of Senses: An ERP Study of Sublexical Ambiguities
      in Reading Chinese Disyllabic Compounds.
AB  - In English, an extensive body of work in both behavioral and neuropsychological
      domains has produced strong evidence that homonymy (words with many distinct
      meanings) and polysemy (many related senses) are represented, retrieved, and
      processed differently in the human brain. In Chinese, most words are compounds,
      and the constituent characters within a compound word can have different meanings
      and/or related senses on their own. Thus, in order to resolve lexical ambiguity
      in Chinese, one has to consider the composition of constituent characters, as
      well as how they contribute to whole word reading, known as "sublexical
      ambiguity." This study investigates how two types of sublexical ambiguity affect
      Chinese word processing. The number of meanings (NOM) and the number of senses
      (NOS) corresponding to the first character of Chinese compounds were manipulated
      in a lexical decision task. The interactions between NOM and NOS were observed in
      both behavioral results and N400s, in which NOM disadvantage effect was found for
      words with few-senses only. On the other hand, the NOS facilitation effect was
      significant for words with multiple-meanings (NOM > 1) only. The sublexical
      ambiguity disadvantage suggested that semantically unrelated morphemes are
      represented as separate entries. For characters with multiple meanings, one
      orthographic form is associated with more than one morphemic representation. In
      contrast, the sublexical sense advantage supported the idea that semantically
      related senses that shared a morphological root are represented within a single
      entry. The more senses listed in a morphological root, the stronger
      representation will be formed. These results suggest that two types of sublexical
      ambiguities are represented and processed differently in Chinese word recognition
      models and also demonstrate that how they interact with each other in the mental
      lexicon.

PMID- 29651262
TI  - The Impact of the Parental Support on Risk Factors in the Process of Gender
      Affirmation of Transgender and Gender Diverse People.
AB  - Research involving transgender and gender diverse people (TGD) increased in the
      last years, mostly concerning healthcare associated to this population. Few
      studies dedicated their analysis to the impact of parental support on transgender
      people, even though this is an important aspect in creating a safe environment on
      which these individuals can build their identity. In addition, the link between
      family support, TGD identity and homelessness is not completely established.
      Thus, due to the specificities of the family context of TGD individuals, the aim
      of this study is to investigate the association between family support and TGD in
      different moments of the process of gender affirmation. In addition, this study
      also aims to explore the relationship between a lack of social support and low
      self-esteem, home abandonment, and dwelling in the street. The survey was
      designed based on the TransPULSE project and was made available in electronic
      format. The sample was constituted of 423 TGD residents in two Brazilian states.
      A Structural Equation Model analysis suggested that the impact of gender
      affirmation status on homelessness was mediated by parental support, through self
      esteem, and the need to move from home. The association between the status of the
      gender affirmation procedures, family support and self-esteem was significant and
      indicated that the further TGD individuals advanced in gender affirmation, the
      more self-esteem and family support they would have. The association between
      family support and self-esteem indicated that family support was associated with
      higher self-esteem. Low family support was associated with the willingness to
      move from home due to one's TGD status and there was also a significant
      correlation between low self-esteem and the willingness to move from home due to
      one's TGD status. Finally, homelessness was associated with the willingness to
      move with a large effect size. Limitations include the sample that was
      constituted by individuals with Internet access and who had more contact with TGD
      communities. The findings indicate directions for interventions involving TGD
      people and their families, considering the parental relationship as a critical
      variable to improve TGD quality of life in the process of gender affirmation.

PMID- 29651261
TI  - Defining the Construct of Synthetic Androgen Intoxication: An Application of
      General Brain Arousal.
AB  - Synthetic androgens (i. e., anabolic-androgenic steroids) are the primary
      component to the majority of problematic appearance and performance enhancing
      drug (APED) use. Despite evidence that these substances are associated with
      increased risk for aggression, violence, body image disturbances, and
      polypharmacy and can develop a pattern of chronic use consistent with drug
      dependence, there are no formal definitions of androgen intoxication.
      Consequently, the purpose of this paper is to establish a testable theory of
      androgen intoxication. We present evidence and theorize that synthetic androgen
      intoxication can be defined by a pattern of poor self-regulation characterized by
      increased propensity for a range of behaviors (e.g., aggression, sex, drug
      seeking, exercise, etc.) via androgen mediated effects on general brain arousal.
      This theory posits that androgens reduce threshold for emotional reactivity,
      motor response, and alertness to sensory stimuli and disrupt inhibitory control
      over the behaviors associated with synthetic androgen use. These changes result
      from alteration to basic neurocircuitry that amplifies limbic activation and
      reduces top-down cortical control. The implications for this definition are to
      inform APED specific hypotheses about the behavioral and psychological effects of
      APED use and provide a basis for establishing clinical, legal, and public health
      guidelines to address the use and misuse of these substances.

PMID- 29651263
TI  - Effect- and Performance-Based Auditory Feedback on Interpersonal Coordination.
AB  - When two individuals interact in a collaborative task, such as carrying a sofa or
      a table, usually spatiotemporal coordination of individual motor behavior will
      emerge. In many cases, interpersonal coordination can arise independently of
      verbal communication, based on the observation of the partners' movements and/or
      the object's movements. In this study, we investigate how social coupling between
      two individuals can emerge in a collaborative task under different modes of
      perceptual information. A visual reference condition was compared with three
      different conditions with new types of additional auditory feedback provided in
      real time: effect-based auditory feedback, performance-based auditory feedback,
      and combined effect/performance-based auditory feedback. We have developed a new
      paradigm in which the actions of both participants continuously result in a
      seamlessly merged effect on an object simulated by a tablet computer application.
      Here, participants should temporally synchronize their movements with a 90
      degrees  phase difference and precisely adjust the finger dynamics in order to
      keep the object (a ball) accurately rotating on a given circular trajectory on
      the tablet. Results demonstrate that interpersonal coordination in a joint task
      can be altered by different kinds of additional auditory information in various
      ways.

PMID- 29651264
TI  - From Innate Spatial Biases to Enculturated Spatial Cognition: The Case of Spatial
      Associations in Number and Other Sequences.

PMID- 29651265
TI  - An Initial Cross-Cultural Comparison of Adult Playfulness in Mainland China and
      German-Speaking Countries.
AB  - Compared with playfulness in infants and children, playfulness in adults is
      relatively under-studied. Although there is no empirical research comparing
      differences in adult playfulness across cultures, one might expect variations
      between Western and Eastern societies such as China. While playfulness is
      typically seen as a positive trait in Western culture, there are hints in Chinese
      culture that being playful has negative connotations (e.g., associations with
      laziness and seeing play as the opposite of work). The aim of this study was to
      compare expressions of playfulness in one sample from German-speaking countries
      (n = 143) and two samples from China (Guangzhou: n = 176; Beijing: n = 100).
      Participants completed one playfulness scale developed in the West (Short Measure
      of Adult Playfulness, SMAP) and one from the East (Adult Playfulness
      Questionnaire, APQ). Additional ratings of the participants were collected to
      measure: (a) the level of playful behavior expressed by people in different
      situations (e.g., when being around family members, in public, or on social
      media), and (b) individuals' perceptions of society's expectations concerning the
      appropriateness of being playful in the given situations. Overall, the results of
      the comparisons were mixed. Although SMAP scores did not vary significantly
      across the three samples, people from German-speaking countries tended to score
      higher on some facets of the APQ and some situational ratings. Stronger effects
      were found when comparing only the German-speaking sample and the Guangzhou
      sample. In addition to the cross-cultural differences that we expected, we also
      detected Chinese regional variations (North vs. South). We conclude that societal
      rules and cultural factors may impact expressions of playfulness in a society.

PMID- 29651266
TI  - Narcissistic Leaders and Their Victims: Followers Low on Self-Esteem and Low on
      Core Self-Evaluations Suffer Most.
AB  - Narcissistic leaders are self-absorbed and hold beliefs of entitlement and
      superiority. Their aggressive tendencies in the face of criticism and
      inclinations to validate their self-worth by derogating others may lead others to
      perceive them as being abusive. Here, we test the relationship between leader
      narcissism and followers' perceptions of abusive supervision. Drawing upon
      research related to the behavioral plasticity hypothesis, we propose that
      followers with low self-esteem will perceive narcissistic leaders as more abusive
      than those with high self-esteem. Followers low on self-esteem are more insecure,
      more in need of approval from their supervisor and are more likely to interpret
      the haughty, derogatory attitude of narcissistic leaders as abusive. Such
      followers also make for 'easier targets' and thus may actually suffer more
      abusive behavior from their narcissistic leaders. In a first multi-source study
      of 85 leaders and 128 followers, we found support for the moderating role of
      follower self-esteem in the relationship between leader narcissism and perceived
      abusive supervision: Narcissistic leaders were rated as more abusive by followers
      who were low on self-esteem, but not those higher on self-esteem. In a second
      multi-source field study among 177 leader-follower dyads, we tested a moderated
      mediation model and showed that this finding also holds for the broader concept
      of follower core self-evaluations as a moderator. Abusive supervision, in turn,
      was related to lower follower performance and followers experiencing more burnout
      symptoms. Thus, followers low on self-esteem or low on core self-evaluations seem
      to suffer most from narcissistic leaders as they perceive them to be abusive and,
      in turn, these followers show reduced performance and more burnout symptoms when
      working for such leaders. This research thus identifies an important moderator
      that might help reconcile previous inconsistent findings regarding perceptions of
      narcissistic leaders.

PMID- 29651267
TI  - Assessment of Affect Lability: Psychometric Properties of the ALS-18.
AB  - Affect lability, an important aspect of emotion dysregulation, characterizes
      several psychiatric conditions. The short Affective Lability Scales (ALS-18)
      measures three aspects of changeability between euthymia and affect states
      (Anxiety/Depression, AD; Depression/Elation, DE; and Anger, Ang). The aim of our
      study was to investigate the psychometric characteristics of an Italian version
      of the ALS-18 in a sample of adults recruited from the general population. The
      sample was composed of 494 adults (343 women and 151 men) aged 18 and higher
      (mean age = 31.73 years, SD = 12.6). All participants were administered a
      checklist assessing socio-demographic variables, the ALS-18 and measures of
      depression and difficulties in emotion regulation. Confirmatory factor analyses
      indicated adequate fit of the three-factor model (RMSEA = 0.061, 95% CI =
      0.054/0.069; CFI = 0.99; SRMR = 0.055), and the presence of a higher-order
      general factor. Internal consistency was satisfactory for all the lower-order
      dimensions and the general factor (ordinal alpha > 0.70). The ALS-18 was
      significantly associated with concurrent measures of depression and difficulties
      in emotion regulation. These findings indicate that the ALS-18 is a valid and
      reliable instrument for measuring affect lability, although discriminant validity
      of subdimensions scores could be problematic.

PMID- 29651268
TI  - Sociocultural Appearance Standards and Risk Factors for Eating Disorders in
      Adolescents and Women of Various Ages.
AB  - The main aim of the present study was to verify the level of impact of
      sociocultural appearance standards (passive awareness and active internalization)
      have on body dissatisfaction, the desire to engage in a relentless pursuit of
      thinness, the adoption of a perfectionistic attitude toward the body, and the
      development of a tendency to engage in bulimic eating behavior, which can develop
      in adolescent girls and women of varying ages. The study group comprised 234
      individuals: 95 secondary school girls, 33 high school girls, 56 female students,
      and 50 employed women, all of whom were living in southern Poland. Participants
      were not diagnosed with any psychiatric disorders (including eating disorders).
      The variables were measured using the Polish version of Garner's Eating Disorder
      Inventory and the Polish Sociocultural Attitudes Towards Physical Appearance and
      Body Image Inventory [based on the SATAQ-3 (Sociocultural Attitudes Towards
      Appearance Questionnaire Scale-3)]. The findings revealed that the youngest
      Polish girls (aged 12-15) reported the highest level of risk factors for eating
      disorders. Among the entire study group, the internalization of appearance
      standards and the pressure associated with various media messages were determined
      to be predictors of the pursuit of thinness, regardless of age and body mass
      index values. The second most significant variable explained by the
      internalization of sociocultural standards was body dissatisfaction. The
      internalization of sociocultural norms provided a significant explanation of
      bulimic tendencies only in the youngest girls. Perfectionism proved not to be
      affected by the sociocultural impact of mass media. The adult women had the
      lowest average scores over the entire study population regarding exposure
      frequency to body images in mass media and regarding the experience of pressure
      exerted by sociocultural norms. The high level of internalization of
      sociocultural appearance standards seems to be significantly linked to body
      satisfaction in women aged 30 and older. Young adolescent girls constitute a high
      risk group for a specific psychological proneness to developing eating disorders
      as a result of the sociocultural influence exerted by mass media. The obtained
      study results can prove helpful in creating education programs in preventive
      healthcare aimed particularly at the youngest adolescents.

PMID- 29651269
TI  - Self-Reported Risk and Delinquent Behavior and Problem Behavioral Intention in
      Hong Kong Adolescents: The Role of Moral Competence and Spirituality.
AB  - Based on the six-wave data collected from Grade 7 to Grade 12 students (N = 3,328
      at Wave 1), this pioneer study examined the development of problem behaviors
      (risk and delinquent behavior and problem behavioral intention) and the
      predictors (moral competence and spirituality) among adolescents in Hong Kong.
      Individual growth curve models revealed that while risk and delinquent behavior
      accelerated and then slowed down in the high school years, adolescent problem
      behavioral intention slightly accelerated over time. After controlling the
      background socio-demographic factors, moral competence and spirituality were
      negatively associated with risk and delinquent behavior as well as problem
      behavioral intention across all waves as predicted. Regarding the rate of change
      in the outcome measures, while the initial level of spirituality was positively
      linked to the growth rate of risk and delinquent behavior, the initial level of
      moral competence was negatively associated with the growth rate of problem
      behavioral intention. The theoretical and practical implications of the present
      findings are discussed with reference to the role of moral competence and
      spirituality in the development of adolescent problem behavior.

PMID- 29651270
TI  - Disparities in Functional Outcome After Intracerebral Hemorrhage Among Asians and
      Pacific Islanders.
AB  - Background: Disparities in outcome after intracerebral hemorrhage (ICH) among
      Asians, Native Hawaiians, and other Pacific Islanders (NHOPI) have been
      inadequately studied. We sought to assess differences in functional outcome
      between Asians and NHOPI after ICH. Methods: A multiracial prospective cohort
      study of ICH patients was conducted from 2011 to 2016 at a tertiary center in
      Honolulu, HI, USA to assess racial disparities in outcome after ICH. Favorable
      outcome was defined as 3-month modified Rankin Scale (mRS) score <=2. Patients
      with no available 3-month functional outcome, race other than Asians and NHOPI,
      and baseline mRS > 0 were excluded. Multivariable analyses using logistic
      regression were performed to assess the impact of race on favorable outcome after
      adjusting for the ICH Score, early do-not-resuscitate (DNR) order and
      dementia/cognitive impairment. Results: A total of 220 patients (161 Asians, 59
      NHOPI) were studied. Overall, 65 (29.5%) achieved favorable outcome at 3 months.
      NHOPI were younger than Asians (p < 0.0001) and had higher prevalence of diabetes
      (p = 0.007), obesity (p < 0.0001), and lower prevalence of dementia/cognitive
      impairment (p = 0.02), early DNR order (p = 0.0004), and advance directive
      presence (p = 0.0005). NHOPI race was a predictor of favorable outcome in the
      unadjusted model [odds ratio (OR) 2.47, 95% confidence interval (CI): 1.32-4.62]
      and after adjusting for the ICH Score (OR 2.30, 95% CI: 1.06-4.97) but not in the
      final model (OR 2.04, 95% CI: 0.94-4.42). In the final model, the ICH Score was
      the only independent negative predictor of outcome (OR 0.26, 95% CI: 0.17-0.41
      per point). Conclusion: NHOPI are more likely to achieve favorable functional
      outcome after ICH compared with Asians even after controlling for ICH severity.
      However, this association was attenuated by the DNR and dementia/cognitive
      impairment status.

PMID- 29651272
TI  - Commentary: Global, regional, and national burden of neurological disorders
      during 1990-2015: a systematic analysis for the Global Burden of Disease Study
      2015.

PMID- 29651271
TI  - Genetics Modulate Gray Matter Variation Beyond Disease Burden in Prodromal
      Huntington's Disease.
AB  - Huntington's disease (HD) is a neurodegenerative disorder caused by an expansion
      mutation of the cytosine-adenine-guanine (CAG) trinucleotide in the HTT gene.
      Decline in cognitive and motor functioning during the prodromal phase has been
      reported, and understanding genetic influences on prodromal disease progression
      beyond CAG will benefit intervention therapies. From a prodromal HD cohort (N =
      715), we extracted gray matter (GM) components through independent component
      analysis and tested them for associations with cognitive and motor functioning
      that cannot be accounted for by CAG-induced disease burden (cumulative effects of
      CAG expansion and age). Furthermore, we examined genetic associations (at the
      genomic, HD pathway, and candidate region levels) with the GM components that
      were related to functional decline. After accounting for disease burden, GM in a
      component containing cuneus, lingual, and middle occipital regions was positively
      associated with attention and working memory performance, and the effect size was
      about a tenth of that of disease burden. Prodromal participants with at least one
      dystonia sign also had significantly lower GM volume in a bilateral inferior
      parietal component than participants without dystonia, after controlling for the
      disease burden. Two single-nucleotide polymorphisms (SNPs: rs71358386 in NCOR1
      and rs71358386 in ADORA2B) in the HD pathway were significantly associated with
      GM volume in the cuneus component, with minor alleles being linked to reduced GM
      volume. Additionally, homozygous minor allele carriers of SNPs in a candidate
      region of ch15q13.3 had significantly higher GM volume in the inferior parietal
      component, and one minor allele copy was associated with a total motor score
      decrease of 0.14 U. Our findings depict an early genetical GM reduction in
      prodromal HD that occurs irrespective of disease burden and affects regions
      important for cognitive and motor functioning.

PMID- 29651273
TI  - Are There Differences in Androgen Receptor Expression in Invasive Breast Cancer
      in African (Tanzanian) Population in Comparison With the Caucasian (Italian)
      Population?
AB  - Purpose: Androgen receptor (AR) has been shown to have prognostic implication on
      breast cancer (BC). Data on the biological features of African BCs are poor. We
      decided for the first time to compare AR expression of Tanzanian and Italian BC
      patients. Patients and methods: Of the 69 consecutive patients seen at the
      Bugando Medical Center (Mwanza, Tanzania) from 2003 to 2010, who underwent
      resection of primary BC evaluable for estrogen receptor, progesterone receptor
      (PgR), and HER2 only 65 were evaluable for AR by immunohistochemistry.
      Histopathological assessment and biomolecular determinations were performed at
      the Cancer Institute of Romagna [Istituto Scientifico Romagnolo per lo studio e
      la cura dei tumori (IRST)-IRCCS, Meldola, Italy]. Caucasian BC patients were
      selected from an electronic database and matched (1:2 ratio) for year of
      diagnosis and age at diagnosis. Results: The median age of patients at diagnosis
      was 51 (range 29-83) years for Tanzanian and 53 (range 26-86) years for Italian
      patients. Tanzanian patients harbored tumors with lower AR expression than
      Italian patients according to the median percentage of immunopositive tumor cells
      (30% versus 80%, p < 0.0001) and staining intensity (p = 0.0003). The proportion
      of AR negative patients was likewise higher among Tanzanian patients as regards
      both >=1% and >=10% cutoffs. AR-positive BCs were higher in luminal A and B
      tumors and decreased in triple-negative (TN) and HER2-enriched tumors in
      Tanzanian population. Conclusion: AR loss could represent an unfavorable
      prognostic marker in the African population. The high frequency of TN tumors with
      high AR expression could open new perspectives of therapy for population in this
      low income country.

PMID- 29651274
TI  - Identification of Unequally Represented Founder Viruses Among Tissues in Very
      Early SIV Rectal Transmission.
AB  - Characterizing the transmitted/founder (T/F) viruses of multi-variant SIV
      infection may shed new light on the understanding of mucosal transmission. We
      intrarectally inoculated six Chinese rhesus macaques with a single high dose of
      SIVmac251 (3.1 * 104 TCID50) and obtained 985 full-length env sequences from
      multiple tissues at 6 and 10 days post-infection by single genome amplification
      (SGA). All 6 monkeys were infected with a range of 2 to 8 T/F viruses and the
      dominant variants from the inoculum were still dominant in different tissues from
      each monkey. Interestingly, our data showed that a cluster of rare T/F viruses
      was unequally represented in different tissues. This cluster of rare T/F viruses
      phylogenetically related to the non-dominant SIV variants in the inoculum and was
      not detected in any rectum tissues, but could be identified in the descending
      colon, jejunum, spleen, or plasma. In 2 out of 6 macaques, identical SIVmac251
      variants belonging to this cluster were detected simultaneously in descending
      colon/jejunum and the inoculum. We also demonstrated that the average CG
      dinucleotide frequency of these rare T/F viruses found in tissues, as well as non
      dominant variants in the inoculum, was significantly higher than the dominant T/F
      viruses in tissues and the inoculum. Collectively, these findings suggest that
      descending colon/jejunum might be more susceptible than rectum to SIV in the very
      early phase of infection. And host CG suppression, which was previously shown to
      inhibit HIV replication in vitro, may also contribute to the bottleneck selection
      during in vivo transmission.

PMID- 29651275
TI  - Structural and Functional Motifs in Influenza Virus RNAs.
AB  - Influenza A viruses (IAV) are responsible for recurrent influenza epidemics and
      occasional devastating pandemics in humans and animals. They belong to the
      Orthomyxoviridae family and their genome consists of eight (-) sense viral RNA
      (vRNA) segments of different lengths coding for at least 11 viral proteins. A
      heterotrimeric polymerase complex is bound to the promoter consisting of the 13
      5'-terminal and 12 3'-terminal nucleotides of each vRNA, while internal parts of
      the vRNAs are associated with multiple copies of the viral nucleoprotein (NP),
      thus forming ribonucleoproteins (vRNP). Transcription and replication of vRNAs
      result in viral mRNAs (vmRNAs) and complementary RNAs (cRNAs), respectively.
      Complementary RNAs are the exact positive copies of vRNAs; they also form
      ribonucleoproteins (cRNPs) and are intermediate templates in the vRNA
      amplification process. On the contrary, vmRNAs have a 5' cap snatched from
      cellular mRNAs and a 3' polyA tail, both gained by the viral polymerase complex.
      Hence, unlike vRNAs and cRNAs, vmRNAs do not have a terminal promoter able to
      recruit the viral polymerase. Furthermore, synthesis of at least two viral
      proteins requires vmRNA splicing. Except for extensive analysis of the viral
      promoter structure and function and a few, mostly bioinformatics, studies
      addressing the vRNA and vmRNA structure, structural studies of the influenza A
      vRNAs, cRNAs, and vmRNAs are still in their infancy. The recent crystal
      structures of the influenza polymerase heterotrimeric complex drastically
      improved our understanding of the replication and transcription processes. The
      vRNA structure has been mainly studied in vitro using RNA probing, but its
      structure has been very recently studied within native vRNPs using crosslinking
      and RNA probing coupled to next generation RNA sequencing. Concerning vmRNAs,
      most studies focused on the segment M and NS splice sites and several structures
      initially predicted by bioinformatics analysis have now been validated
      experimentally and their role in the viral life cycle demonstrated. This review
      aims to compile the structural motifs found in the different RNA classes (vRNA,
      cRNA, and vmRNA) of influenza viruses and their function in the viral replication
      cycle.

PMID- 29651276
TI  - Liposome Entrapment of Bacteriophages Improves Wound Healing in a Diabetic Mouse
      MRSA Infection.
AB  - Diabetic populations are more prone to developing wound infections which results
      in poor and delayed wound healing. Infection with drug resistant organisms
      further worsen the situation, driving searches for alternative treatment
      approaches such as phage therapy. Major drawback of phage therapy, however, is
      low phage persistence in situ, suggesting further refinement of the approach. In
      the present work we address this issue by employing liposomes as delivery
      vehicles. A liposome entrapped phage cocktail was evaluated for its ability to
      resolve a Staphylococcus aureus-induced diabetic excission wound infection. Two
      characterized S. aureus specific lytic phages, MR-5 and MR-10 alone, in
      combination (cocktail), or entrapped in liposomes (versus as free phages) were
      assesed for their therapeutic efficacy in resolving diabetic wound infection.
      Mice treated with free phage cocktail showed significant reduction in wound
      bioburden, greater wound contraction and faster tissue healing than with free
      monophage therapy. However, to further enhance the availability of viable phages
      the encapsulation of phage cocktail in the liposomes was done. Results of in
      vitro stability studies and in vivo phage titer determination, suggests that
      liposomal entrapment of phage cocktail can lead to better phage persistence at
      the wound site. A 2 log increase in phage titre, however, was observed at the
      wound site with liposome entrapped as compared to the free phage cocktail, and
      this was associaed with increased rates of infection resolution and wound
      healing. Entrapment of phage cocktails within liposomes thus could represent an
      attractive approach for treatment of bacterial infections, not responding to
      antibiotis as increased phage persistence in vitro and in vivo at the wound site
      was observed.

PMID- 29651277
TI  - New Delhi Metallo-Beta-Lactamase-Producing Enterobacteriaceae in South Korea
      Between 2010 and 2015.
AB  - This study was carried out to investigate the epidemiological time-course of New
      Delhi metallo-beta-lactamase- (NDM-) mediated carbapenem resistance in
      Enterobacteriaceae in South Korea. A total of 146 non-duplicate NDM-producing
      Enterobacteriaceae recovered between 2010 and 2015 were voluntarily collected
      from 33 general hospitals and confirmed by PCR. The species were identified by
      sequences of the 16S rDNA. Antimicrobial susceptibility was determined either by
      the disk diffusion method or by broth microdilution, and the carbapenem MICs were
      determined by agar dilution. Then, multilocus sequence typing and PCR-based
      replicon typing was carried out. Co-carried genes for drug resistance were
      identified by PCR and sequencing. The entire genomes of eight random selected NDM
      producers were sequenced. A total of 69 Klebsiella pneumoniae of 12 sequence
      types (STs), 34 Escherichia coli of 15 STs, 28 Enterobacter spp. (including one
      Enterobacter aerogenes), nine Citrobacter freundii, four Raoultella spp., and two
      Klebsiella oxytoca isolates produced either NDM-1 (n = 126), NDM-5 (n = 18), or
      NDM-7 (n = 2). The isolates co-produced CTX-M-type ESBL (52.1%), AmpCs (27.4%),
      additional carbapenemases (7.1%), and/or 16S rRNA methyltransferases (4.8%),
      resulting in multidrug-resistance (47.9%) or extensively drug-resistance (52.1%).
      Among plasmids harboring blaNDM, IncX3 was predominant (77.4%), followed by the
      IncFII type (5.8%). Genome analysis revealed inter-species and inter-strain
      horizontal gene transfer of the plasmid. Both clonal dissemination and plasmid
      transfer contributed to the wide dissemination of NDM producers in South Korea.

PMID- 29651278
TI  - Editorial: Genome Invading RNA Networks.

PMID- 29651279
TI  - Effect of the Secondary Symbiont Hamiltonella defensa on Fitness and Relative
      Abundance of Buchnera aphidicola of Wheat Aphid, Sitobion miscanthi.
AB  - Bacterial symbionts associated with insects are often involved in host
      development and ecological fitness. In aphids, the role of these symbionts is
      variable and not fully understood across different host species. Here, we
      investigated the symbiont diversity of the grain aphid, Sitobion miscanthi
      (Takahashi), from 17 different geographical areas. Of these, two strains with the
      same symbiont profile, except for the presence of Hamiltonella defensa, were
      selected using PCR. The Hamiltonella-infected strain, YX, was collected from a
      Yuxi wheat field in Yunnan Province, China. The Hamiltonella-free strain, DZ, was
      collected from a Dezhou wheat field in Shandong Province, China. Using artificial
      infection with H. defensa and antibiotic treatment, a Hamiltonella-re-infected
      strain (DZ-H) and Hamiltonella-significantly decreased strain (DZ-HT) were
      established and compared to the Hamiltonella-free DZ strain in terms of
      ecological fitness. Infection with the DZ-H strain increased the fitness of S.
      miscanthi, which led to increases in adult weight, percent of wingless
      individuals, and number of offspring. Meanwhile, decreased abundance of H.
      defensa (DZ-HT strain) resulted in a lower adult weight and wingless aphid rate
      compared to the DZ-H strain. However, the indices of longevity in both the DZ-H
      and DZ-HT strains decreased slightly, but were not significantly different,
      compared to the DZ strain. Furthermore, quantitative PCR showed that the relative
      abundance of the primary symbiont Buchnera aphidicola in the DZ-H strain was
      significantly higher than in the DZ strain in all but the first developmental
      stage. These results indicate that H. defensa may indirectly improve the fitness
      of S. miscanthi by stimulating the proliferation of B. aphidicola.

PMID- 29651280
TI  - Collective Vortex-Like Movement of Bacillus subtilis Facilitates the Generation
      of Floating Biofilms.
AB  - Bacteria in nature are usually found in complex multicellular structures, called
      biofilms. One common form of a biofilm is pellicle-a floating mat of bacteria
      formed in the water-air interphase. So far, our knowledge on the basic mechanisms
      underlying the formation of biofilms at air-liquid interfaces is not complete. In
      particular, the co-occurrence of motile cells and extracellular matrix producers
      has not been studied. In addition, the potential involvement of chemical
      communication in pellicle formation remained largely undefined. Our results
      indicate that vortex-like collective motility by aggregates of motile cells and
      EPS producers accelerate the formation of floating biofilms. Successful
      aggregation and migration to the water-air interphase depend on the chemical
      communication signal autoinducer 2 (AI-2). This ability of bacteria to form a
      biofilm in a preferable niche ahead of their potential rivals would provide a
      fitness advantage in the context of inter-species competition.

PMID- 29651281
TI  - The Potential of Isolation Source to Predict Colonization in Avian Hosts: A Case
      Study in Campylobacter jejuni Strains From Three Bird Species.
AB  - Campylobacter jejuni is the primary cause of bacterial gastroenteritis worldwide,
      infecting humans mostly through consumption of contaminated poultry. C. jejuni is
      common in the gut of wild birds, and shows distinct strain-specific association
      to particular bird species. This contrasts with farm animals, in which several
      genotypes co-exist. It is unclear if the barriers restricting transmission
      between host species of such specialist strains are related to environmental
      factors such as contact between host species, bacterial survival in the
      environment, etc., or rather to strain specific adaptation to the intestinal
      environment of specific hosts. We compared colonization dynamics in vivo between
      two host-specific C. jejuni from a song thrush (ST-1304 complex) and a mallard
      (ST-995), and a generalist strain from chicken (ST-21 complex) in a wild host,
      the mallard (Anas platyrhynchos). In 18-days infection experiments, the song
      thrush strain showed only weak colonization and was cleared from all birds after
      10 days, whereas both mallard and chicken strains remained stable. When the
      chicken strain was given 4 days prior to co-infection of the same birds with a
      mallard strain, it was rapidly outcompeted by the latter. In contrast, when the
      mallard strain was given 4 days prior to co-infection with the chicken strain,
      the mallard strain remained and expansion of the chicken strain was delayed. Our
      results suggest strain-specific differences in the ability of C. jejuni to
      colonize mallards, likely associated with host origin. This difference might
      explain observed host association patterns in C. jejuni from wild birds.

PMID- 29651282
TI  - Effect of Cinnamaldehyde and Citral Combination on Transcriptional Profile,
      Growth, Oxidative Damage and Patulin Biosynthesis of Penicillium expansum.
AB  - Penicillium expansum, as a main postharvest pathogen of fruits, can secrete
      patulin (PAT), causing fruit decay and health problems. In this study, the
      antifungal test, SEM (scanning electron microscope) observation, transcriptional
      profile, PAT biosynthesis, and physiological characters of P. expansum exposed to
      cinnamaldehyde and citral combination (Cin/Cit) were evaluated. Cin/Cit could
      inhibit the mycelial growth and spore germination of P. expansum in a dose
      dependent manner. Besides, Cin/Cit caused spores and mycelia wrinkled and
      depressed by SEM observation. Gene expression profiles of P. expansum were
      conducted by RNA sequencing (RNA-seq) in the presence or absence of Cin/Cit
      treatment. A total of 1713 differentially expressed genes (DEGs) were obtained,
      including 793 down-regulated and 920 up-regulated genes. Most of the DEGs
      participated in the biosynthesis of secondary metabolites, amino acid metabolism,
      and oxidation-reduction process, etc. Cin/Cit induced the dysfunction of the
      mitochondrial membrane, causing the potential influence on energy metabolism and
      reactive oxidative species production. The changes of superoxide dismutase (SOD)
      and catalase (CAT) activities combing with the increase of hydrogen peroxide
      content indicated the oxidative stress on P. expansum induced by Cin/Cit, which
      corresponded well with the transcriptional results. Moreover, both the RNA-seq
      data and the qRT-PCR showed the remarkable down-regulation of genes included in
      the PAT biosynthetic pathway under the Cin/Cit treatment. These findings provided
      more useful information about the antifungal mechanism of Cin/Cit against P.
      expansum at molecular and gene levels and suggested that Cin/Cit is a potential
      candidate to control P. expansum.

PMID- 29651285
TI  - Atomic Force Microscopy of Side Wall and Septa Peptidoglycan From Bacillus
      subtilis Reveals an Architectural Remodeling During Growth.
AB  - Peptidoglycan is the fundamental structural constituent of the bacterial cell
      wall. Despite many years of research, the architecture of peptidoglycan is still
      largely elusive. Here, we report the high-resolution architecture of
      peptidoglycan from the model Gram-positive bacterium Bacillus subtilis. We
      provide high-resolution evidence of peptidoglycan architecture remodeling at
      different growth stages. Side wall peptidoglycan from B. subtilis strain AS1.398
      changed from an irregular architecture in exponential growth phase to an ordered
      cable-like architecture in stationary phase. Thickness of side wall peptidoglycan
      was found to be related with growth stages, with a slight increase after
      transition to stationary phase. Septal disks were synthesized progressively
      toward the center, while the surface features were less clear than those imaged
      with side walls. Compared with previous studies, our results revealed slight
      differences in architecture of peptidoglycan from different B. subtilis strains,
      expanding our knowledge about the architectural features of B. subtilis
      peptidoglycan.

PMID- 29651284
TI  - Transcriptomic and Ectoine Analysis of Halotolerant Nocardiopsis gilva YIM 90087T
      Under Salt Stress.
AB  - The genus Nocardiopsis is an unique actinobacterial group that widely distributed
      in hypersaline environments. In this study, we investigated the growth
      conditions, transcriptome analysis, production and accumulation of ectoine by
      Nocardiopsis gilva YIM 90087T under salt stress. The colony color of N. gilva YIM
      90087T changed from yellow to white under salt stress conditions. Accumulation of
      ectoine and hydroxyectoine in cells was an efficient way to regulate osmotic
      pressure. The ectoine synthesis was studied by transferring the related genes
      (ectA, ectB, and ectC) to Escherichia coli. Transcriptomic analysis showed that
      the pathways of ABC transporters (ko02010) and glycine, serine, and threonine
      metabolism (ko00260) played a vital role under salt stress environment. The
      ectABC from N. gilva YIM 90087T was activated under the salt stress. Addition of
      exogenous ectoine and hydroxyectoine were helpful to protect N. gilva YIM 90087T
      from salt stress.

PMID- 29651283
TI  - miRNAs in Tuberculosis: New Avenues for Diagnosis and Host-Directed Therapy.
AB  - Tuberculosis (TB) is one of the most fatal infectious diseases and a leading
      cause of mortality, with 95% of these deaths occurring in developing countries.
      The causative agent, Mycobacterium tuberculosis (Mtb), has a well-established
      ability to circumvent the host's immune system for its intracellular survival.
      microRNAs (miRNAs) are small, non-coding RNAs having an important function at the
      post-transcriptional level and are involved in shaping immunity by regulating the
      repertoire of genes expressed in immune cells. It has been established in recent
      studies that the innate immune response against TB is significantly regulated by
      miRNAs. Moreover, differential expression of miRNA in Mtb infection can reflect
      the disease progression and may help distinguish between active and latent TB
      infection (LTBI). These findings encouraged the application of miRNAs as
      potential biomarkers. Similarly, active participation of miRNAs in modulation of
      autophagy and apoptosis responses against Mtb opens an exciting avenue for the
      exploitation of miRNAs as host directed therapy (HDT) against TB. Nanoparticles
      mediated delivery of miRNAs to treat various diseases has been reported and this
      technology has a great potential to be used in TB. In reality, this exploitation
      of miRNAs as biomarkers and in HDT is still in its infancy stage, and more
      studies using animal models mimicking human TB are advocated to assess the role
      of miRNAs as biomarkers and therapeutic targets. In this review, we attempt to
      summarize the recent advancements in the role of miRNAs in TB as immune
      modulator, miRNAs' capability to distinguish between active and latent TB and,
      finally, usage of miRNAs as therapeutic targets against TB.

PMID- 29651286
TI  - IgA Targeting Human Immunodeficiency Virus-1 Envelope gp41 Triggers Antibody
      Dependent Cellular Cytotoxicity Cross-Clade and Cooperates with gp41-Specific IgG
      to Increase Cell Lysis.
AB  - The protective efficacy of human immunodeficiency virus-1 (HIV-1) antibodies
      (Abs) remains mostly correlated with their in vitro neutralizing activity
      engaging their Fab region. However, anti-HIV-1 Abs also mediate a broad array of
      Fc-mediated effector functions including Ab-dependent cellular cytotoxicity
      (ADCC), which depend primarily on the Ab isotype. While ADCC is commonly
      associated with HIV-1 gp120 envelope-specific IgGs, whether IgAs, especially
      those targeting the HIV-1 gp41 envelope, also mediate ADCC remains elusive.
      Therefore, to assess the capacity of IgA specific for HIV-1 to induce Fcalpha
      mediated ADCC, we used the gp41 envelope-specific IgA transformed from the
      broadly neutralizing 2F5-IgG we have previously reported to induce ADCC. We
      demonstrate that 2F5-IgA engages FcalphaRI (CD89), expressed on human monocytes
      used as effector cells, to induce the lysis of HIV-1 Clade A- and B-infected
      target cells by ADCC. Furthermore, the 2F5-IgA and 2F5-IgG cooperate to enhance
      target cells lysis by ADCC. Cooperation in ADCC is also observed between 2F5-IgA
      and the broadly neutralizing 10E8-IgG. These results provide a new perspective
      for IgA in protection against HIV-1 acquisition or reservoir eradication and
      suggest that inducing IgA by vaccination, in particular when targeting gp41, in
      combination with IgG could strengthen protection by complementary and cooperative
      activities with IgG.

PMID- 29651287
TI  - Neutralizing Anti-Cytokine Autoantibodies Against Interferon-alpha in
      Immunodysregulation Polyendocrinopathy Enteropathy X-Linked.
AB  - Anti-cytokine autoantibodies (ACAAs) have been described in a growing number of
      primary immunodeficiencies with autoimmune features, including autoimmune
      polyendocrine syndrome type I (APS-1), a prototypical disease of defective T cell
      mediated central tolerance. Whether defects in peripheral tolerance lead to
      similar ACAAs is unknown. Immunodysregulation polyendocrinopathy enteropathy X
      linked (IPEX) is caused by mutations in FOXP3, a master regulator of T regulatory
      cells (Treg), and consequently results in defective T cell-mediated peripheral
      tolerance. Unique autoantibodies have previously been described in IPEX. To test
      the hypothesis that ACAAs are present in IPEX, we designed and fabricated antigen
      microarrays. We discovered elevated levels of IgG ACAAs against interferon-alpha
      (IFN-alpha) in a cohort of IPEX patients. Serum from IPEX patients blocked IFN
      alpha signaling in vitro and blocking activity was tightly correlated with ACAA
      titer. To show that blocking activity was mediated by IgG and not other serum
      factors, we purified IgG and showed that blocking activity was contained entirely
      in the immunoglobulin fraction. We also screened for ACAAs against IFN-alpha in a
      second geographically distinct cohort. In these samples, ACAAs against IFN-alpha
      were elevated in a post hoc analysis. In summary, we report the discovery of
      ACAAs against IFN-alpha in IPEX, an experiment of nature demonstrating the
      important role of peripheral T cell tolerance.

PMID- 29651288
TI  - CEBPE-Mutant Specific Granule Deficiency Correlates With Aberrant Granule
      Organization and Substantial Proteome Alterations in Neutrophils.
AB  - Specific granule deficiency (SGD) is a rare disorder characterized by abnormal
      neutrophils evidenced by reduced granules, absence of granule proteins, and
      atypical bilobed nuclei. Mutations in CCAAT/enhancer-binding protein-epsilon
      (CEBPE) are one molecular etiology of the disease. Although C/EBPepsilon has been
      studied extensively, the impact of CEBPE mutations on neutrophil biology remains
      elusive. Here, we identified two SGD patients bearing a previously described
      heterozygous mutation (p.Val218Ala) in CEBPE. We took this rare opportunity to
      characterize SGD neutrophils in terms of granule distribution and protein
      content. Granules of patient neutrophils were clustered and polarized, suggesting
      that not only absence of specific granules but also defects affecting other
      granules contribute to the phenotype. Our analysis showed that remaining granules
      displayed mixed protein content and lacked several glycoepitopes. To further
      elucidate the impact of mutant CEBPE, we performed detailed proteomic analysis of
      SGD neutrophils. Beside an absence of several granule proteins in patient cells,
      we observed increased expression of members of the linker of nucleoskeleton and
      cytoskeleton complex (nesprin-2, vimentin, and lamin-B2), which control nuclear
      shape. This suggests that absence of these proteins in healthy individuals might
      be responsible for segmented shapes of neutrophilic nuclei. We further show that
      the heterozygous mutation p.Val218Ala in CEBPE causes SGD through prevention of
      nuclear localization of the protein product. In conclusion, we uncover that
      absence of nuclear C/EBPepsilon impacts on spatiotemporal expression and
      subsequent distribution of several granule proteins and further on expression of
      proteins controlling nuclear shape.

PMID- 29651290
TI  - Anti-Transforming Growth Factor beta IgG Elicits a Dual Effect on Calcium Oxalate
      Crystallization and Progressive Nephrocalcinosis-Related Chronic Kidney Disease.
AB  - Crystallopathies are a heterogeneous group of diseases caused by intrinsic or
      environmental microparticles or crystals, promoting tissue inflammation and
      scarring. Certain proteins interfere with crystal formation and growth, e.g.,
      with intrarenal calcium oxalate (CaOx) crystal formation, a common cause of
      kidney stone disease or nephrocalcinosis-related chronic kidney disease (CKD). We
      hypothesized that immunoglobulins can modulate CaOx microcrystal formation and
      crystal growth and that therefore, biological IgG-based drugs designed to
      specifically target disease modifying proteins would elicit a dual effect on the
      outcome of CaOx-related crystallopathies. Indeed, both the anti-transforming
      growth factor (TGF)beta IgG and control IgG1 antibody impaired CaOx
      crystallization in vitro, and decreased intrarenal CaOx crystal deposition and
      subsequent CKD in mice on an oxalate-rich diet compared to oxalate-fed control
      mice. However, the TGFbeta-specific IgG antibody showed nephroprotective effects
      beyond those of control IgG1 and substantially reduced interstitial fibrosis as
      indicated by magnetic resonance imaging, silver and alpha-smooth muscle actin
      staining, RT-qPCR, and flow cytometry for pro-fibrotic macrophages. Suppressing
      interstitial fibrosis slowed the decline of glomerular filtration rate (GFR)
      compared to treatment with control IgG1 [slope of m = -8.9 vs. m = -14.5
      MUl/min/100 g body weight (BW)/day, Delta = 38.3%], an increased GFR at the end
      of the study (120.4 vs. 42.6 MUl/min/100 g BW, Delta = 64.6%), and prolonged end
      stage renal disease (ESRD)-free renal survival by 10 days (Delta = 38.5%).
      Delayed onset of anti-TGFbeta IgG from day 7 was no longer effective. Our results
      suggest that biological drugs can elicit dual therapeutic effects on intrinsic
      crystallopathies, such as anti-TGFbeta IgG antibody treatment inhibits CaOx
      crystallization as well as interstitial fibrosis in nephrocalcinosis-related CKD.

PMID- 29651289
TI  - Development and Characterization of an Endotoxemia Model in Zebra Fish.
AB  - Endotoxemia is a condition in which endotoxins enter the blood stream and cause
      systemic and sometimes lethal inflammation. Zebra fish provides a genetically
      tractable model organism for studying innate immunity, with additional advantages
      in live imaging and drug discovery. However, a bona fide endotoxemia model has
      not been established in zebra fish. Here, we have developed an acute endotoxemia
      model in zebra fish by injecting a single dose of LPS directly into the
      circulation. Hallmarks of human acute endotoxemia, including systemic
      inflammation, extensive tissue damage, circulation blockade, immune cell
      mobilization, and emergency hematopoiesis, were recapitulated in this model.
      Knocking out the adaptor protein Myd88 inhibited systemic inflammation and
      improved zebra fish survival. In addition, similar alternations of pathways with
      human acute endotoxemia were detected using global proteomic profiling and
      MetaCoreTM pathway enrichment analysis. Furthermore, treating zebra fish with a
      protein tyrosine phosphatase nonreceptor type 11 (Shp2) inhibitor decreased
      systemic inflammation, immune mobilization, tissue damage, and improved survival
      in the endotoxemia model. Together, we have established and characterized the
      phenotypic and gene expression changes of a zebra fish endotoxemia model, which
      is amenable to genetic and pharmacological discoveries that can ultimately lead
      to a better mechanistic understanding of the dynamics and interplay of the innate
      immune system.

PMID- 29651291
TI  - Cutting an NKG2D Ligand Short: Cellular Processing of the Peculiar Human NKG2D
      Ligand ULBP4.
AB  - Stress-induced cell surface expression of MHC class I-related glycoproteins of
      the MIC and ULBP families allows for immune recognition of dangerous "self cells"
      by human cytotoxic lymphocytes via the NKG2D receptor. With two MIC molecules
      (MICA and MICB) and six ULBP molecules (ULBP1-6), there are a total of eight
      human NKG2D ligands (NKG2DL). Since the discovery of the NKG2D-NKG2DL system, the
      cause for both redundancy and diversity of NKG2DL has been a major and ongoing
      matter of debate. NKG2DL diversity has been attributed, among others, to the
      selective pressure by viral immunoevasins, to diverse regulation of expression,
      to differential tissue expression as well as to variations in receptor
      interactions. Here, we critically review the current state of knowledge on the
      poorly studied human NKG2DL ULBP4. Summarizing available facts and previous
      studies, we picture ULBP4 as a peculiar ULBP family member distinct from other
      ULBP family members by various aspects. In addition, we provide novel
      experimental evidence suggesting that cellular processing gives rise to mature
      ULBP4 glycoproteins different to previous reports. Finally, we report on the
      proteolytic release of soluble ULBP4 and discuss these results in the light of
      known mechanisms for generation of soluble NKG2DL.

PMID- 29651293
TI  - Homeobox a5 Promotes White Adipose Tissue Browning Through Inhibition of the
      Tenascin C/Toll-Like Receptor 4/Nuclear Factor Kappa B Inflammatory Signaling in
      Mice.
AB  - Lipopolysaccharide (LPS) induces rapid increase in systemic inflammatory factors.
      As adipose tissue is a key contributor to the inflammatory response to numerous
      metabolic stimuli, it is important to understand the mechanism behind the LPS
      induced inflammation in white adipose tissue (WAT). Homeobox a5 (Hoxa5) is an
      important transcription factor, which is highly expressed in adipose tissue, and
      its mRNA expression is increased at cold exposure in mice. So far, the function
      of Hoxa5 in adipose tissue browning has been poorly understood. So, the objective
      of this study was conducted to determine the role of Hoxa5 in adipose
      inflammatory response and white adipose browning in mice. LPS-induced
      inflammatory and cold-induced browning model were conducted. We compared the
      coordinated role of Hoxa5 in inflammation and thermogenesis of mice adipose.
      Transcriptional and methylation regulation was determined by luciferase assay,
      electrophoretic mobility shift assay, and bisulfite conversion experiment. Hoxa5
      and tenascin C (TNC) were involved in WAT inflammation and browning in mice with
      LPS injection. Furthermore, Hoxa5 inhibited the TNC-involved activation of Toll
      like receptor (TLR) 4/nuclear factor kappa B (NF-kappaB) signal pathway and
      promoted WAT browning. Moreover, we found that a BMP4/Smad1 signal, closely
      related to browning, was activated by Hoxa5. Hoxa5 relieved adipocyte
      inflammation by decreasing TNC-mediated TLR4 transducer and activator of the NF
      kappaB pathway. Interestingly, descended methylation level increased Hoxa5
      expression in cold exposure. Our findings demonstrated that Hoxa5 alleviated
      inflammation and enhanced browning of adipose tissue via negative control of
      TNC/TLR4/NF-kappaB inflammatory signaling and activating BMP4/Smad1 pathway.
      These findings indicated a novel potential means for the regulation of
      inflammation in adipocytes to prevent obesity and other inflammatory diseases.

PMID- 29651292
TI  - Autoantibodies to Chemokines and Cytokines Participate in the Regulation of
      Cancer and Autoimmunity.
AB  - We have previously shown that predominant expression of key inflammatory
      cytokines and chemokines at autoimmune sites or tumor sites induces loss of B
      cells tolerance, resulting in autoantibody production against the dominant
      cytokine/chemokine that is largely expressed at these sites. These autoantibodies
      are high-affinity neutralizing antibodies. Based on animal models studies, we
      suggested that they participate in the regulation of cancer and autoimmunity,
      albeit at the level of their production cannot entirely prevent the development
      and progression of these diseases. We have, therefore, named this selective
      breakdown of tolerance as "Beneficial Autoimmunity." Despite its beneficial
      outcome, this process is likely to be stochastic and not directed by a
      deterministic mechanism, and is likely to be associated with the dominant
      expression of these inflammatory mediators at sites that are partially immune
      privileged. A recent study conducted on autoimmune regulator-deficient patients
      reported that in human this type of breakdown of B cell tolerance is T cell
      dependent. This explains, in part, why the response is highly restricted, and
      includes high-affinity antibodies. The current mini-review explores this subject
      from different complementary perspectives. It also discusses three optional
      translational aspects: amplification of autoantibody production as a therapeutic
      approach, development of autoantibody based diagnostic tools, and the use of B
      cells from donors that produce these autoantibodies for the development of high
      affinity human monoclonal antibodies.

PMID- 29651294
TI  - Lateral Root Development in Potato Is Mediated by Stu-mi164 Regulation of NAC
      Transcription Factor.
AB  - The NAC designation is derived from petunia (Petunia hybrida) gene NO APICAL
      MERISTEM (NAM) and Arabidopsis genes ATAF1/ATAF2 and CUP-SHAPED COTYLEDON2
      (CUC2), which belongs to the family of plant-specific transcription factors
      (TFs), and plays important role in plant development processes, such as response
      to biotic and abiotic stress, and hormone signaling. MicroRNAs (miRNAs) are a
      class of small, non-coding endogenous RNAs which play versatile and significant
      role in plant stress response and development via negatively affecting gene
      expression at a post-transcriptional level. Here, we showed that Stu-mi164 had a
      complementary sequence in the CDS sequence of potato NAC TFs, and that NAC
      expression exhibited significant differences under osmotic stress. We measured
      expression levels of the Stu-mi164 target gene StNAC262 between control and PEG
      treated plants using real-time PCR, and the results demonstrated that they had
      inverse relationship. We suggested that Stu-miR164 might drive overexpression of
      NAC gene under osmotic stress in potato. To confirm the regulation of NAC TFs by
      Stu-mi164, we developed transgenic plants, using Agrobacterium tumefaciens
      mediated transformation, of the potato cultivars "Gannongshu 2" and "Kexin 3"
      overexpressing the Stu-mi164 or the TF StNAC262. Real-time PCR analysis of
      transgenic potato plants under osmotic (PEG) stress, showed that potato plants
      overexpressing Stu-mi164 had reduced expression of StNAC262 and their osmotic
      resistance decreased. Furthermore, these plants had low number of lateral roots
      although the same length as the control. Our findings support the regulatory role
      of Stu-miRNAs in controlling plant response to osmotic stress via StNAC262.

PMID- 29651295
TI  - Development and Phenotypic Screening of an Ethyl Methane Sulfonate Mutant
      Population in Soybean.
AB  - Soybean is an important oil-producing crop in the Fabaceae family and there are
      increasing demands for soybean oil and other soybean products. Genetic
      improvement of soybean is needed to increase its production. In order to provide
      genetic diversity and resources for identifying important genes, a new ethyl
      methane sulfonate (EMS) mutagenized soybean population was generated using the
      newly released germplasm, JTN-5203 (maturity group V). Treatment of soybean seeds
      with 60 mM EMS concentration was found to be suitable for inducing mutation. A
      total of 1,820 M1 individuals were produced from 15,000 treated seeds. The
      resulting M2 population was planted in the field for phenotyping. After harvest,
      seed traits including total oil, protein, starch, moisture content, fatty acid
      and amino acid compositions were measured by NIR. Phenotypic variations observed
      in this population include changes in leaf morphology, plant architecture, seed
      compositions, and yield. Of most interest, we identified plants with increased
      amounts of total protein (50% vs. 41% for control) and plants with higher amounts
      of total oil (25% vs. 21.2% control). Similarly, we identified plants with
      increases in oleic acid content and decreases in linoleic acid and linolenic
      acid. This EMS mutant population will be used for further studies including
      screening for various traits such as amino acid pathways, allergens, phytic
      acids, and other important soybean agronomic traits. In addition, these mutant
      individuals will be evaluated in the next generation to assess the heritability.
      Beneficial traits from these mutants can be exploited for future soybean breeding
      programs. This germplasm can also be used for discovering novel mutant alleles
      and for functional gene expression analysis using reverse genetics tools such as
      TILLING.

PMID- 29651296
TI  - Association Mapping for Important Agronomic Traits in Safflower (Carthamus
      tinctorius L.) Core Collection Using Microsatellite Markers.
AB  - Carthamus tinctorius L. (safflower) is an important oilseed crop producing seed
      oil rich in unsaturated fatty acids. Scarcity of identified marker-trait
      associations is a major limitation toward development of successful marker
      assisted breeding programs in safflower. In the present study, a safflower panel
      (CartAP) comprising 124 accessions derived from two core collections was assayed
      for its suitability for association mapping. Genotyping of CartAP using
      microsatellite markers revealed significant genetic diversity indicated by
      Shannon information index (H = 0.7537) and Nei's expected heterozygosity (I =
      0.4432). In Principal Coordinate Analysis, the CartAP accessions were distributed
      homogeneously in all quadrants indicating their diverse nature. Distance-based
      Neighbor Joining analysis did not delineate the CartAP accessions in consonance
      with their geographical origin. Bayesian analysis of population structure of
      CartAP demonstrated the unstructured nature of the association panel. Kinship
      analysis at population (Gij ) and individual level (Fij ) revealed absence of or
      weak relatedness between the CartAP accessions. The above parameters established
      the suitability of CartAP for association mapping. We performed association
      mapping using phenotypic data for eight traits of agronomic value (viz., seed oil
      content, oleic acid, linoleic acid, plant height, number of primary branches,
      number of capitula per plant, 100-seed weight and days to 50% flowering)
      available for two growing seasons (2011-2012 and 2012-2013) through General
      Linear Model and Mixed Linear Model. Our study identified ninety-six significant
      marker-trait associations (MTAs; P < 0.05) of which, several MTAs with
      correlation coefficient (R2) > 10% were consistently represented in both models
      and in both seasons for traits viz., oil content, oleic acid content, linoleic
      acid content and number of primary branches. Several MTAs with high R2-values
      were detected either in a majority or in some environments (models and/or
      seasons). Many MTAs were also common between traits (viz., oleic/linoleic acid
      content; plant height/days to 50% flowering; number of primary branches/number of
      capitula per plant) that showed positive or negative correlation in their
      phenotypic values. The marker-trait associations identified in this study will
      facilitate marker-assisted breeding and identification of genetic determinants of
      trait variability.

PMID- 29651297
TI  - Niclosamide Blocks Rice Leaf Blight by Inhibiting Biofilm Formation of
      Xanthomonas oryzae.
AB  - Rice (Oryza sativa) is the leading source of nutrition for more than half of the
      world's population, and by far it is the most important commercial food crop.
      But, its growth and production are significantly hampered by the bacterial
      pathogen Xanthomonas oryzae pv. oryzae (Xoo) which causes leaf blight disease.
      Earlier studies have reported the antibacterial ability of FDA-approved
      niclosamide drug against Xoo. However, the underlying mechanism by which
      niclosamide blocks the growth of Xoo remained elusive. In the present study, by
      employing the microbiological, microscopical, molecular, bioinformatics and
      analytical tools we found that niclosamide can directly inhibit the growth of the
      Xoo by hampering the biofilm formation and the production of xanthomonadin and
      exopolysaccharide substances (EPS) required for relentless growth and virulence
      of Xoo. Interestingly, niclosamide was found to specifically suppress the growth
      of Xoo without affecting other bacteria like Escherichia coli. Our electron
      microscopic observations disclosed that niclosamide disrupts the membrane
      permeability of Xoo and causes the release of intracellular components.
      Similarly, the molecular docking analysis disclosed the molecular interaction of
      niclosamide with the biofilm, virulence and quorum sensing related proteins,
      which was further substantiated by relative gene expression analysis where
      niclosamide was found to significantly downregulate the expression of these key
      regulatory genes. In addition, considerable changes in chemical structures were
      detected by Fourier Transform Infrared Spectroscopy (FTIR) in response to
      niclosamide treatment. Overall, our findings advocate the utilization of
      niclosamide as a safe and potent alternative antibacterial compound to control
      bacterial blight disease in rice.

PMID- 29651298
TI  - True or false coral snake: is it worth the risk? A Micrurus corallinus case
      report.
AB  - Background: Bites provoked by the genus Micrurus represent less than 1% of
      snakebite cases notified in Brazil, a tiny fraction compared with other genus
      such as Bothrops and Crotalus, which together represent almost 80% of accidents.
      In addition to their less aggressive behavior, habits and morphology of coral
      snakes are determinant factors for such low incidence of accidents. Although
      Micrurus bites are rare, victims must be rescued and hospitalized in a short
      period of time, because this type of envenoming may evolve to a progressive
      muscle weakness and acute respiratory failure. Case Presentation: We report an
      accident caused by Micrurus corallinus involving a 28-year-old Caucasian sailor
      man bitten on the hand. The accident occurred in a recreational camp because
      people believed the snake was not venomous. The victim presented neurological
      symptoms 2 h after the accident and was taken to the hospital, where he received
      antielapidic serum 10 h after the bite. After the antivenom treatment, the
      patient presented clinical evolution without complications and was discharged 4
      days later. Conclusions: We reinforce that it is essential to have a health care
      structure suitable for the treatment of snakebite. Besides, the manipulation of
      these animals should only be carried out by a team of well-equipped and trained
      professionals, and even so with special attention.

PMID- 29651299
TI  - A leukocyte activation test identifies food items which induce release of DNA by
      innate immune peripheral blood leucocytes.
AB  - Background: Leukocyte activation (LA) testing identifies food items that induce a
      patient specific cellular response in the immune system, and has recently been
      shown in a randomized double blinded prospective study to reduce symptoms in
      patients with irritable bowel syndrome (IBS). We hypothesized that test
      reactivity to particular food items, and the systemic immune response initiated
      by these food items, is due to the release of cellular DNA from blood immune
      cells. Methods: We tested this by quantifying total DNA concentration in the
      cellular supernatant of immune cells exposed to positive and negative foods from
      20 healthy volunteers. To establish if the DNA release by positive samples is a
      specific phenomenon, we quantified myeloperoxidase (MPO) in cellular
      supernatants. We further assessed if a particular immune cell population
      (neutrophils, eosinophils, and basophils) was activated by the positive food
      items by flow cytometry analysis. To identify the signaling pathways that are
      required for DNA release we tested if specific inhibitors of key signaling
      pathways could block DNA release. Results: Foods with a positive LA test result
      gave a higher supernatant DNA content when compared to foods with a negative
      result. This was specific as MPO levels were not increased by foods with a
      positive LA test. Protein kinase C (PKC) inhibitors resulted in inhibition of
      positive food stimulated DNA release. Positive foods resulted in CD63 levels
      greater than negative foods in eosinophils in 76.5% of tests. Conclusion: LA test
      identifies food items that result in release of DNA and activation of peripheral
      blood innate immune cells in a PKC dependent manner, suggesting that this LA test
      identifies food items that result in release of inflammatory markers and
      activation of innate immune cells. This may be the basis for the improvement in
      symptoms in IBS patients who followed an LA test guided diet.

PMID- 29651300
TI  - A concise classification of bencao (materia medica).
AB  - Books that record the sources and applications of medicinal materials are
      commonly known as bencao (materia medica) in China. Bencao (materia medica)
      literature review is the very first step in the standard authentication procedure
      of Chinese medicinals. As an important part of China's cultural heritage, these
      various bencao (materia medica) texts represent centuries of accumulated wisdom
      in combating disease and preserving health. In this short review, bencao (materia
      medica) classics of China are broadly divided into three major categories in our
      routine practice: mainstream bencao (materia medica), thematic bencao (materia
      medica) and regional bencao (materia medica). The overall significance and
      current situation of exploration of bencao (materia medica) literature are
      summarized as well.

PMID- 29651301
TI  - Caregiver experiences of public services following child trauma exposure: a
      qualitative study.
AB  - Background: Many children in low and middle income countries (LMIC) are exposed
      to trauma. Contact with public services are a potential influence on parent-child
      reactions and coping post-trauma. Little is known about how caregivers perceive
      these interactions. Methods: The aim of this study was to explore caregivers'
      experiences of accessing and interacting with public services post-trauma and
      perceptions of needed improvements to public services in a LMIC context.
      Qualitative interviews were conducted with 20 female caregivers from a high-risk
      settlement in South Africa after child trauma exposure. Results: Three themes and
      seven sub-themes were identified regarding caregivers' perceptions of
      interactions with public services post-trauma. The key themes identified related
      to (1) communication and exchanges with law enforcement, (2) consequences of an
      under-resourced justice system and (3) importance of communication and empathy in
      the healthcare system. Interactions with police were often positive. However,
      caregivers explained that police-family communication post-trauma could be
      improved and may help to lessen caregiver anxiety and concerns for the child's
      safety post-trauma. Caregivers perceived the judicial system to be under
      resourced as contact with the judicial system was often protracted and caused
      child anxiety and distress. Medical treatment was reportedly rushed, with
      extensive waiting times and little information provided to caregivers regarding
      the child's injuries or treatment. Some medical staff were perceived as
      unsympathetic during the child's treatment which was found to exacerbate
      caregiver and child distress post-trauma. Conclusions: This study provides
      insight into caregiver experiences of accessing public services following child
      trauma exposure in a high-risk LMIC context. Public services were perceived as
      oversubscribed and under-resourced and negative interactions often influenced
      caregiver responses and appraisals of child safety. Given the impact of poor
      interactions with public services on families post-trauma, additional research is
      needed to investigate feasible improvements to public services in LMIC.

PMID- 29651302
TI  - Common mental disorders and psychological adjustment among individuals seeking
      HIV testing: a study protocol to explore implications for mental health care
      systems.
AB  - Background: In an effort to promote greater access to voluntary counseling and
      testing for HIV, it has become practice in many countries, including South
      Africa, to establish non-medical testing sites and to de-couple HIV testing from
      other medical and mental health care services. While it is well established that
      HIV infection is associated with a range of psychopathology, much of the
      literature has assumed that it is receipt of an HIV positive diagnosis that
      causes people to become depressed, traumatized, or develop other psychiatric
      symptoms. Empirical data about the baseline psychiatric condition and mental
      health care needs of persons seeking HIV testing is scarce. Understanding the
      psychological health of persons seeking HIV testing and documenting how
      psychiatric symptoms develop over time following receipt of an HIV positive
      diagnosis, has important implications for mental health care systems. Methods: We
      describe a study protocol to investigate: (1) the level of psychological distress
      and the prevalence of common mental disorders among persons seeking HIV testing;
      (2) the longitudinal development of psychiatric symptoms among persons diagnosed
      with HIV; and (3) the recommendations that can be made for mental health care
      systems to support persons seeking HIV testing and those newly diagnosed with
      HIV. In this longitudinal study quantitative and qualitative data are collected
      to document participants' psychiatric symptoms, to determine whether they meet
      diagnostic criteria for a common mental disorder, and to explore the lived
      experiences of persons receiving an HIV positive test result. Data are collected
      at three time points; before HIV testing, and then again at 6 and 12 months post
      testing. Discussion: Documenting the prevalence of common mental disorders among
      persons seeking HIV testing, and tracking the psychosocial support needs,
      psychological adjustment and psychosocial experiences of persons newly diagnosed
      with HIV, has important implications for the delivery of mental health care
      services and the design of integrated mental health care systems.

PMID- 29651303
TI  - Reproducible, high-yielding, biological caproate production from food waste using
      a single-phase anaerobic reactor system.
AB  - Background: Nowadays, the vast majority of chemicals are either synthesised from
      fossil fuels or are extracted from agricultural commodities. However, these
      production approaches are not environmentally and economically sustainable, as
      they result in the emission of greenhouse gases and they may also compete with
      food production. Because of the global agreement to reduce greenhouse gas
      emissions, there is an urgent interest in developing alternative sustainable
      sources of chemicals. In recent years, organic waste streams have been
      investigated as attractive and sustainable feedstock alternatives. In particular,
      attention has recently focused on the production of caproate from mixed culture
      fermentation of low-grade organic residues. The current approaches for caproate
      synthesis from organic waste are not economically attractive, as they involve the
      use of two-stage anaerobic digestion systems and the supplementation of external
      electron donors, both of which increase its production costs. This study
      investigates the feasibility of producing caproate from food waste (FW) without
      the supplementation of external electron donors using a single-phase reactor
      system. Results: Replicate leach-bed reactors were operated on a semi-continuous
      mode at organic loading of 80 g VS FW l-1 and at solid retention times of 14 and
      7 days. Fermentation, rather than hydrolysis, was the limiting step for caproate
      production. A higher caproate production yield 21.86 +/- 0.57 g COD l-1 was
      achieved by diluting the inoculating leachate at the beginning of each run and by
      applying a leachate recirculation regime. The mixed culture batch fermentation of
      the FW leachate was able to generate 23 g caproate COD l-1 (10 g caproate l-1),
      at a maximum rate of 3 g caproate l-1 day-1 under high H2 pressure. Lactate
      served as the electron donor and carbon source for the synthesis of caproate.
      Microbial community analysis suggested that neither Clostridium kluyveri nor
      Megasphaera elsdenii, which are well-characterised caproate producers in
      bioreactors systems, were strongly implicated in the synthesis of caproate, but
      that rather Clostridium sp. with 99% similarity to Ruminococcaceae bacterium CPB6
      and Clostridium sp. MT1 likely played key roles in the synthesis of caproate.
      This finding indicates that the microbial community capable of caproate synthesis
      could be diverse and may therefore help in maintaining a stable and robust
      process. Conclusions: These results indicate that future, full-scale, high-rate
      caproate production from carbohydrate-rich wastes, associated with biogas
      recovery, could be envisaged.

PMID- 29651304
TI  - Managing diabetic foot infections: a survey of Australasian infectious diseases
      clinicians.
AB  - Background: Diabetic foot infections (DFI) present a major morbidity, mortality
      and economic challenge for the tertiary health sector. However, lack of high
      quality evidence for specific treatment regimens for patients with DFIs may
      result in inconsistent management. This study aimed to identify DFI caseload
      proportion and patterns of clinical practice of Infectious Diseases (ID)
      Physicians and Trainees within Australia and New Zealand. Methods: A cross
      sectional online survey of Australian and New Zealand ID Physicians and Trainees
      was undertaken, to estimate the overall ID caseload devoted to patients with DFIs
      and assess clinicians' management practices of patients with DFIs. Results:
      Approximately 28% (142/499) of ID Physicians and Trainees from Australia and New
      Zealand responded to the survey. DFI made up 19.2% of all ID consultations.
      Involvement in multidisciplinary teams (MDT) was common as 77.5% (93/120) of
      those responding indicated their patients had access to an inpatient or
      outpatient MDT. Significant heterogeneity of antimicrobial treatments was
      reported, with 82 unique treatment regimens used by 102 respondents in one
      scenario and 76 unique treatment regimens used by 101 respondents in the second
      scenario. The duration of therapy and the choice of antibiotics for
      microorganisms isolated from superficial swabs also varied widely. Conclusions:
      Patients with DFIs represent a significant proportion of an ID clinician's
      caseload. This should be reflected in the ID training program. Large
      heterogeneity in practice between clinicians reflects a lack of evidence from
      well-designed clinical trials for patients with DFI and highlights the need for
      management guidelines informed by future trials.

PMID- 29651305
TI  - Student perceptions of the education environment in a Spanish medical podiatry
      school.
AB  - Background: The aim of this study was to explore students' perceptions of the
      educational environment (EE) in a Spanish school of podiatry. Various aspects of
      EE were compared by academic year in the program. Methods: This was a cross
      sectional study using a questionnaire to collect perceptions using data from a
      2015 survey. Podiatric medical students from Extremadura University participated
      in this study. EE was assessed with the Dundee Ready Education Environment
      Measure (DREEM) tool.The DREEM questionnaire covers five domains of student
      perceptions, including learning, teachers, academic self-perceptions, atmosphere,
      and social self-perceptions. Results: Two hundred thirty-five students
      participated, resulting in a 90.73% response rate. Participants included similar
      numbers of students from different years in the program, and most were women. The
      global EE score was 2.58 out of 4, indicating that students' perceptions were
      more positive than negative. Although some weaknesses were detected in this
      school, students viewed the EE positively in all five DREEM domains. Academic
      year in the program were generally not related to perceptions of EE. Conclusions:
      Podiatric medical students declared, in general, that the EE was more positive
      than negative in our school, according to the DREEM questionnaire. However,
      although the results are on the whole good, some areas need to be revised to make
      improvements.

PMID- 29651306
TI  - Association of mean platelet volume with incident type 2 diabetes mellitus risk:
      the Dongfeng-Tongji cohort study.
AB  - Background: Most of prior studies to demonstrate the association between mean
      platelet volume (MPV) and type 2 diabetes mellitus (T2DM) risk were cross
      sectional design with inconsistent results. In the present prospective cohort
      study, we aimed to explore the relationship between MPV and incident T2DM risk
      among a middle-aged and older Chinese population. Methods: This prospective study
      included 14,009 individuals derived from the Dongfeng-Tongji cohort which was
      launched in 2008. A total of 997 incident T2DM patients were diagnosed during the
      mean 4.51 years of follow-up period. MPV levels were divided into quartiles. The
      adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) of incident
      T2DM was estimated by Cox proportional hazard models. Results: Compared with
      study participants with MPV < 7.49 fL, the HRs of T2DM incidence were 1.39 (95%
      CI 1.11-1.75), 1.14 (0.90-1.44), and 1.39 (95% CI 1.07-1.81) in study
      participants with 7.49 <= MPV < 8.43 fL, 8.43 fL <= MPV < 9.69 fL and MPV >= 9.69
      fL, respectively. This positive association was more pronounced after exclusion
      of the newly diagnosed incident cases during the first 2 years follow-up. Further
      adjustment for baseline fasting blood glucose level (FBG) did not materially
      alter the positive association. The positive association was particularly evident
      among females, non-current smokers and study participants with FBG level less
      than 5.6 mmol/L at baseline. Conclusion: Higher levels of MPV were independently
      associated with increased incident risk of T2DM in a middle-aged and older
      Chinese population.

PMID- 29651307
TI  - Effectiveness of gliclazide MR 60 mg in the management of type 2 diabetes:
      analyses from the EASYDia trial.
AB  - Background: Although the number of antihyperglycemic agents has expanded
      significantly, sulfonylureas (in particular gliclazide) remain an important
      option because of a variety of patient and health system factors. The large, real
      world, observational, and international EASYDia trial evaluated the effectiveness
      of gliclazide modified release (MR) 60 mg in individuals with type 2 diabetes
      with a broad range of diabetes history, body mass index (BMI) and background
      antihyperglycemic treatment. Methods: A total of 7170 participants from eight
      countries, age >= 35 years with HbA1c >= 7.5% and not treated with insulin, were
      prescribed 30-120 mg of gliclazide MR 60 mg once daily. HbA1c goals were
      individualized and dosing uptitrated, as required, over the 6-month long study.
      In this post hoc subanalysis, efficacy endpoints were analyzed according to
      stratified baseline HbA1c levels, weight and glucose-lowering regimens. Episodes
      of hypoglycemia requiring assistance were documented. Results: At baseline, mean
      age was 58.9 years, HbA1c 8.8%, BMI 30.1 kg/m2, and diabetes duration 5.1 years.
      At study end, clinically significant HbA1c improvements (mean change - 1.78%)
      were noted across all baseline HbA1c strata (> 7.0 to <= 8.0%, > 8.0 to <= 9.0%,
      > 9.0 to <= 10.0%, and > 10.0%), BMI classifications (18.5 to < 25.0, 25.0 to <
      30.0, and >= 30.0 kg/m2), and regardless of the original diabetes treatment
      regimen (P < 0.001 in all cases). In contrast to the subgroups with BMI 25.0-30.0
      and >= 30.0 kg/m2 that registered weight losses of 0.9 and 2.2 kg, respectively
      (P < 0.001 vs. baseline weight); the BMI 18.5-24.9 kg/m2 subgroup gained a mean
      0.5 kg (P < 0.02 vs. baseline weight). Severe hypoglycemic events were rare
      (0.06%). Conclusions: Progressive gliclazide MR 60 mg uptitration was well
      tolerated and lowered HbA1c across a broad range of HbA1c, BMI and background
      glucose-lowering therapy. Weight loss was noted when BMI was >= 25.0 kg/m2.
      Individuals with the highest baseline HbA1c and BMI experienced the greatest
      HbA1c and weight improvements.Trial registration ISRCTN Registry ISRCTN00943368
      on 1st July 2011.

PMID- 29651308
TI  - DART-MS analysis of inorganic explosives using high temperature thermal
      desorption.
AB  - An ambient mass spectrometry (MS) platform coupling resistive Joule heating
      thermal desorption (JHTD) and direct analysis in real time (DART) was implemented
      for the analysis of inorganic nitrite, nitrate, chlorate, and perchlorate salts.
      The resistive heating component generated discrete and rapid heating ramps and
      elevated temperatures, up to approximately 400  degrees C s-1 and 750  degrees C,
      by passing a few amperes of DC current through a nichrome wire. JHTD enhanced the
      utility and capabilities of traditional DART-MS for the trace detection of
      previously difficult to detect inorganic compounds. A partial factorial design of
      experiments (DOE) was implemented for the systematic evaluation of five system
      parameters. A base set of conditions for JHTD-DART-MS was derived from this
      evaluation, demonstrating sensitive detection of a range of inorganic oxidizer
      salts, down to single nanogram levels. DOE also identified JHTD filament current
      and in-source collision induced dissociation (CID) energy as inducing the
      greatest effect on system response. Tuning of JHTD current provided a method for
      controlling the relative degrees of thermal desorption and thermal decomposition.
      Furthermore, in-source CID provided manipulation of adduct and cluster
      fragmentation, optimizing the detection of molecular anion species. Finally, the
      differential thermal desorption nature of the JHTD-DART platform demonstrated
      efficient desorption and detection of organic and inorganic explosive mixtures,
      with each desorbing at its respective optimal temperature.

PMID- 29651309
TI  - Causes of Differences in The Uptake of Cardiac Implantation Electronic Devices in
      Slovenia in Comparison To Other Countries.
AB  - Introduction: The purpose of this study is to analyse and present the causes of
      the differences in crude utilization rate in cardiac implantation electronic
      devices, specifically pacemakers and automatic implantable cardioverter
      defibrillators, across 5 European countries, with a specific emphasis on
      Slovenia. Methods: Based on the results of the analysis of the uptake of cardiac
      implantation electronic devices across countries studied in MedtecHTA project,
      the targeted interviews were conducted to explain the factors that impact the
      differences and explain data in Slovenia. Results: The reasons for the
      differences in crude utilization rate across 5 European countries were multiple:
      the first group of differences refers to the coding system and linkages between
      coding and financing of health care. The second group of reasons can be
      qualitatively ascribed to the economic situation, financial situation in health
      care, and its impact on decision-making. The last reason is the non-existence of
      the golden rule for optimal crude utilisation rate. Conclusions: It is evident
      that the differences in the uptake of cardiac implantation electronic devices
      among the countries are of organisational nature: they refer to the system of
      coding, the importance attached to correct coding practices, the link between
      coding and financing of health care as well as the availability of private
      clinics and private insurance. According to the interviews, the economic
      development of the country also impacts those differences, whereas the
      differences in clinical practice and guidelines are claimed not to play a role in
      the explanation of the differences.

PMID- 29651310
TI  - A Temporal Profile of pro-abstinence-oriented Constructs from The Modified Theory
      of Planed Behavior in a Slovenian Clinical Sample of Treated Alcoholics - an 18
      year Follow-up.
AB  - Introduction: Using the modified Theory of Planned Behaviour (mTPB), different
      indicators of therapeutic success were studied to understand pro-abstinence
      behavioural orientation during an 18-year after-care period following a 3-month
      intensive alcoholism treatment. The indicators were: perceived needs satisfaction
      (NS), normative differential (ND), perceived alcohol utility (UT), beliefs about
      treatment programme benefits (BE) and behavioural intentions (BI). Methods: The
      sample of 167 patients who consecutively started an intensive alcoholism
      treatment programme has been followed-up for 18 years, using standardised ailed
      instruments at the end of the treatment, and in the years 4-5, 9 and 18 of follow
      up. The last data collection was completed by 32 subjects in 2010. The analysis
      followed the standard explore-analyse-explore approach. After the initial
      descriptive exploration of data, multivariate analysis of variance (MANOVA) in
      SPSS statistical package was set to explore between-groups and within-groups
      differences over time. Results: At the between-group level, BI remained stable at
      the same level as at the end of the treatment programme, whereas BE and UT
      robustly changed over time and levelled off after 10 years of follow-up. NS and
      ND show a trend of pro-abstinent orientation and level off after 10 years of
      follow-up, although the trend is not significant. The same results were confirmed
      by the within-subject level. Conclusions: Studied constructs stabilised after ten
      years of follow-up, apart from BI. The latter suggests that BI level needed for
      completion of an intensive treatment programme suffices for the maintenance of
      abstinence when accompanied by the change in perception of alcohol usefulness.

PMID- 29651311
TI  - The Importance of The Occupational Vocal Load for The Occurence and Treatment of
      Organic Voice Disorders.
AB  - Introduction: The voice represents a basic working tool for carrying out certain
      occupations. Hoarseness, as a consequence of vocal fold lesions, presents an
      important cause of work-related absences for voice professionals. Methods: Our
      study was designed as a retrospective cohort one. Data on gender, workplace,
      vocal load and exposure to risk factors for voice disorders of the patients who
      had surgery in the 2014-2015 period at the tertiary centre due to benign vocal
      fold lesions were collected from their clinical records. We compared professional
      voice users (PVU) to subjects with no vocal load at work (NPVU). The SPSS
      programme, version 22.0, was used for statistical analysis. Results: From 2014 to
      2015, 103 PVU and 132 NPVU were surgically treated for benign vocal fold lesions.
      In comparison to the second group, loud speech use was reported significantly
      more often by PVU (40.8% vs. 14.4%), as was a fast speaking rate (22.3% vs. 9.8%)
      and additional vocal load outside of the workplace (23.3% vs. 12.9%). The time
      that had passed between the occurrence of the hoarseness and the surgical
      treatment did not differ between the groups. The majority of patients were
      satisfied with the outcome of the operation. Conclusions: Nearly a half of the
      operated patients had a considerable vocal load at work. An ENT assessment prior
      to starting a job as well as priority phoniatric treatment of voice disorders for
      PVU would significantly reduce the costs of work absences and contribute to a
      speedier recovery and return to the workplace.

PMID- 29651312
TI  - Increasing Postural Deformity Trends and Body Mass Index Analysis in School-age
      Children.
AB  - Introduction: The aim of the study was to analyse the deviations of the body
      posture and to assess the occurrence of spine deformities. Additionally, Body
      Mass Index in school children was related to the trend in postural deformities
      for different age groups (5-8 years old, n=112; 9-11 years old, n=205; 12-14
      years old, n=212) as part of the project "Spine Lab", granted from the European
      Commission IPA founds, investigating the importance of public health issues.
      Methods: Body posture was measured using Contemplas 3D software analyser, based
      on video image trajectory and BIA weight scale (Tanita BC 420). Overall, 17
      variables were assessed, and differences were confirmed using MANOVA analysis.
      Results: The results showed that there is a significant difference between age
      groups for the measured variables (F=9.27; p<0.01; eta2=0.26), suggesting a
      moderate difference across the age span. Conclusion: The study results showed
      that there is a negative trend of increasing Body Mass Index within the first and
      youngest age group. The fact is that the trend of increasing deformity of the
      shoulder belt has been noted, often inclining towards the formation of milder
      forms of kyphotic posture. Other forms of deformity that are accentuated in the
      survey results are the negative trend of increasing pelvic rotation and pelvis
      rotation which inclines towards the formation of lordotic posture for all three
      age groups.

PMID- 29651313
TI  - Risk Factors for Osteoporosis in Postmenopausal Women - from The Point of View of
      Primary Care Gynecologist.
AB  - Introduction: Osteoporosis is a highly prevalent public health problem with
      osteoporosis-related fractures that account for high morbidity and mortality.
      Therefore, prevention strategies and early detection of osteoporosis should be
      carried out in primary gynaecological care units, so as to substantially reduce
      the risk of fractures and allow the best treatment option for a particular woman.
      Methods: From 2002 to 2011, we recruited 2956 women. Of the total number of
      women, we additionally extrapolated 1274 women aged 60-75 years, assumingly, the
      group of women at higher risk of osteoporosis. Demographic and anthropometrical
      data as well as the information regarding risk factors for osteoporosis were
      collected using a questionnaire. Results: The odds ratio for osteoporosis
      increased by 8% (p=0.001) with each additional year of life. The OP prevalence
      increased with age from 24.9% in 60-64 years to 37.4% in 70-75 years. In non
      smokers the odds ratio for osteoporosis was 0.424, which was statistically
      significant (p<0.05). BMI <18.5 increased the odds ratio for osteoporosis by 2
      times, which was not statistically significant. In women 60-75 years old
      (N=1274), the risk of fractures increased with increasing age, considering
      previous fractures in the last 5 years (p<0.001), hip fracture (p=0.001), wrist
      fracture (p=0.002) and observed height loss (p<0.001). Hormone therapy (HT) use
      decreased the prevalence of OP by 25% in comparison with non-users. Conclusion:
      Primary care gynaecologist with a DXA centre has every opportunity for a holistic
      approach to the management of postmenopausal women, including the prevention and
      treatment of postmenopausal osteoporosis.

PMID- 29651314
TI  - Health Behavior and Health-related Quality of Life in Patients with a High Risk
      of Cardiovascular Disease.
AB  - Background: Health-related quality of life (HRQoL) is measuring a patient's
      experience of his health status and represents an outcome of medical
      interventions. Existing data proves that a healthy lifestyle is positively
      associated with HRQoL in all age groups. Patients with a high risk for
      cardiovascular disease typically led an unhealthy lifestyle combined with risk
      diseases. We aimed to analyse these characteristics and their reflection in
      HRQoL. Methods: A cross-sectional study in 36 family practices, stratified by
      location and size. Each practice invited 30 high-risk patients from the register.
      Data were obtained from medical records and patient questionnaire. The EQ-5D
      questionnaire and the VAS scale were used for measuring the patient's HRQoL as an
      independent variable. Results: 871 patients (80.6% response rate) were included
      in the analysis. 60.0% had 3-4 uncontrolled risk factors for CVD. The average VAS
      scale was 63.2 (SD 19.4). The correlation of EQ-5D was found in the number of
      visits in the practice (r=-0.31, p<0.001), the socioeconomic status (r=-0.25,
      p=0.001), age (r=-0.27, p=0.001) and healthy diet (r=0.20, p=0.006). In a
      multivariate model, only physical activity among lifestyle characteristics was an
      independent predictor of HRQoL (p=0.001, t=3.3), along with the frequency of
      visits (p<0.001, t=-5.3) and age (p=0.025, t=-2.2). Conclusion: This study has
      been performed on a specific group of patients, not being "really sick", but
      having less optimal lifestyle in many cases. Encouragement to improve or keep
      healthy lifestyle, especially physical activity, is important, not only to lower
      the risk for CVD, but also to improve HRQoL.

PMID- 29651315
TI  - Slovenian Version of The European Deprivation Index at Municipal Level.
AB  - Introduction: Ecological deprivation indices belong to essential instruments for
      monitoring and understanding health inequalities. Our aim was to develop the SI
      EDI, a newly derived European Deprivation Index for Slovenia. We intend to
      provide researchers and policy-makers in our country with a relevant tool for
      measuring and reducing the socioeconomic inequalities in health, and even at a
      broader level. Methods: Data from the European survey on Income and Living
      Conditions and Slovenian national census for the year 2011 were used in the SI
      EDI construction. The concept of relative deprivation was used where deprivation
      refers to unmet need(s), which is caused by lack of all kinds of resources, not
      only material. The SI-EDI was constructed for 210 Slovenian municipalities. Its
      geographical distribution was compared to the distribution of two existing
      deprivation scores previously applied in health inequality research in Slovenia.
      Results: There were 36% of adults recognized as deprived in Slovenia in 2011. SI
      EDI was calculated using 10 census variables that were associated with individual
      deprivation. A clear east-to-west gradient was detected with the most deprived
      municipalities in the eastern part of the country. The two existing deprivation
      scores correlate significantly with the SI-EDI. Conclusions: A new deprivation
      index, the SI-EDI, is grounded on the internationally established scientific
      concept, can be replicated over time and, crucially, provides an account of the
      socioeconomic and cultural particularities of the Slovenian population. The SI
      EDI could be used by the stakeholders and the governmental and nongovernmental
      sectors in Slovenia, with the goal of better understanding health inequalities in
      Slovenia.

PMID- 29651317
TI  - Risk of Potential Exposure Incident in Non-healthcare Workers in Contact with
      Infectious and Municipal Waste.
AB  - Introduction: The proper classification of sharp and infectious waste in situ by
      the healthcare workers is an important measure of prevention of sharps and other
      exposure incidents in non-healthcare workers, who handle such waste. The aim was
      to examine the practice of classifying sharp and infectious waste in family and
      dental practices. Methods: An analysis of 50 bags of infectious and 50 bags of
      municipal waste from five family and five dental practices for five days in
      October 2016 at the Health centre Osijek. Results: Healthcare workers in 70% of
      the practices deposited sharps in infectious waste. In 56% of infectious waste
      bags, sharp object were found. More risky bags of infectious waste were produced
      by family practices (64%), but with no significant differences in relation to
      dental practices (48%), (P=0.143). Disposing of infectious into municipal waste
      was the case in 90% of the practitioners, where in 60% of municipal waste bags,
      infectious waste was disposed. Dental practices produced more risky bags of
      municipal waste (76%) in relation to family practices (44%), but with no
      significant difference (P=0.714). Conclusions: The results of this research point
      to importance of performing audits of proper disposal of sharps and infectious
      waste to reduce the risks of injury to non-healthcare workers who come into
      contact with the said waste. Given results could be used for framing written
      protocols of proper disposal of sharps and infectious waste that should be
      visibly available in family and dental practices and for education of healthcare
      workers.

PMID- 29651316
TI  - Early Identification of Patients in Need of Palliative Care in Slovenian General
      Practice.
AB  - Background: To help general practitioners (GPs) in early identification of
      patients with palliative care (PC) needs, this pilot study aimed to determine the
      potential of the combined original surprise question (SQ1) ('Would I be surprised
      if this patient died within the next 12 months?') and the second surprise
      question (SQ2) ('Would I be surprised if this patient was still alive after 12
      months?'). We hypothesized that answering these SQs would trigger them to make a
      multidimensional care plan. Methods: 26 Slovenian GPs, randomized into 4 groups,
      were invited to write a care plan for each of the four patients described in case
      vignettes (2 oncologic, 1 organ failure and 1 frailty case). GPs in group 1 were
      only asked to write a care plan for each patient. GPs in group 2 answered SQ1 and
      GPs in groups 3 and 4 answered SQ1 and SQ2 before writing the care plan. The type
      and number of PC aspects mentioned in the respective care plans were quantified
      into a numeric RADboud ANTicipatory (RADIANT) score. Results: Mean RADIANT scores
      in groups 1-4 were 2.2, 3.6, 2.5 and 3.1, respectively. When comparing the
      different vignettes, vignette B (terminal oncologic patient) scored best (3.6).
      Mean RADIANT scores in groups 3 and 4 were slightly higher for GPs who would be
      surprised compared to GPs who would not be surprised if the patient was still
      alive in 12 months. Conclusion: The combined SQs were considered helpful in the
      early identification of patients in need of PC in Slovenian general practice.

PMID- 29651318
TI  - The Prevalence of Elevated Blood Pressure in a Sample of Slovene Children and
      Adolescents: a Pilot Study.
AB  - Introduction: The aim of our study was to determine the prevalence of
      prehypertensive and elevated blood pressure in the hypertensive range (elevated
      BP) and obtain some anthropometric measures in Slovene children and adolescents.
      Methods: In the cross-sectional study lasting one year, we measured BP using
      mercury sphygmomanometers, as well as height, weight, waist, and hip
      circumferences in schools. Data from regular check-ups (oscillometric
      measurements) were also added to increase the sample size. Participants were 2-19
      years old. For statistical analysis, we used two-sided multivariate analysis of
      variance, Pearson's r, and chi-squared test. Results: From altogether 1594
      participants, 723 (45.4%) were boys and 871 (54.6%) girls. The prevalence of
      elevated BP on a single oscillometric blood-pressure measurement was 12.0% (95%
      CI: 10.3 to 13.9), and an additional 13.9% (95% CI: 12.0 to 15.9) had
      prehypertensive BP. In Riva-Rocci measurements, elevated BP was present in only
      7.1% (95% CI: 4.9 to 10.1) and prehypertensive BP additionally in 3.9% (95% CI:
      2.4 to 6.4) in comparison to oscillometric measurements, which showed higher
      prevalence. Importantly, overweight participants had a 1.75 times greater
      relative risk for prehypertensive BP (95% CI: 1.22 to 2.53; p<0.01). Obesity
      carried a 1.79 times greater relative risk (95% CI: 1.22 to 2.63; p<0.01) for BP
      outside of the normotensive BP range. Conclusion: Arterial hypertension is
      becoming an important public health problem, especially due to the childhood
      obesity. It seems to concern also Slovene young population with prevalence of
      elevated BP at around 7.1% after a single auscultatory BP measurement.

PMID- 29651319
TI  - Effects of Perinatal Factors on Body Mass Index and Physical Fitness of School
      age Children.
AB  - Objective: To examine the effects of various maternal and neonatal perinatal
      factors on the child's body mass index (BMI) and physical fitness at school-age.
      Methods: Data from two registries, the SLOfit database (a national surveillance
      system of children's motor and physical development) and Slovenian National
      Perinatal Information System (NPIS) were analysed. Perinatal data for 2,929
      children born in 2008 were linked to results of SLOfit testing of these children
      in 2016. Linear regression analysis was used to assess the potential relationship
      between several perinatal factors (very preterm birth, birth mass, maternal age,
      hypertensive disorders of pregnancy, gestational diabetes, parity, plurality,
      maternal pre-pregnancy BMI, mode of delivery, presentation, Apgar score at 5
      minutes, and admission to a neonatal intensive care unit (NICU)) and child's BMI
      or child's physical fitness index (PFI) at the age of eight years. We also
      included child's school grade and maternal educational level in the analysis. A p
      value <0.05 was considered statistically significant. Results: Children born to
      mothers with lower pre-pregnancy BMI and higher education had lower BMI and
      higher PFI (p<0.001) at school-age. Physical fitness was also inversely
      associated with nulliparity (p<0.001) and NICU admission (p=0.020). Conclusions:
      Among all perinatal factors studied, higher maternal education and lower pre
      pregnancy BMI seem to be the most significant determinants of child's BMI and
      physical fitness at school-age.

PMID- 29651320
TI  - Movement Activity Determination with Health-related Variables of University
      Students in Kosice.
AB  - Introduction: There is currently a strong scientific evidence about the negative
      health consequences of physical inactivity. One of the potential tools for
      promoting physical activity at the institutional level of the Ecological model is
      to create conditions and settings that would enable pupils, students and
      employees engage in some form of physical activity. However, physical activities
      as a subject are being eliminated from the study programs at Slovak universities.
      The purpose of the study was to find current evidence about the level of
      structured physical activity and health-related variables in university students
      in Kosice. Material and methods: The sample consisted of 1,993 or, more
      precisely, 1,398 students who attended two universities in Kosice. To collect
      data, students completed a questionnaire and were tested for body height, body
      weight, circumferential measures and percentage body fat. Results: The university
      students did not sufficiently engage in a structured physical activity. A large
      number of students had either low or high values of percentage body fat and BMI
      and high WHR values. Conclusions: Our findings have shown that the research into
      physical activity of university students should receive more attention.

PMID- 29651321
TI  - Specialty Training in Family Medicine in Montenegro - an Evaluation of The
      Programme By the First Generation of Trainees.
AB  - Introduction: One of the aims of health care reform in Montenegro is to
      strengthen primary care. An important step forward is the implementation of
      specialty training in family medicine (FM). The aim of this article is to
      evaluate the implementation of specialty training in family medicine in
      Montenegro, regarding the content, structure and methods, by the first generation
      of trainees and the coordinator of the training. Methods: A questionnaire was
      sent by mail in July and August 2017 to all 26 eligible trainees who started
      specialty training in 2013. Twenty-two of the 26 trainees (84.6%) responded. The
      questionnaire consisted of closed and open-ended questions related to the
      evaluation of the training. A descriptive quantitative and qualitative analysis
      with predefined themes and a semi-structured interview with the coordinator were
      carried out. Results: The process of training in FM was assessed positively by
      both trainees and the coordinator. The positive assessment included that the
      specialisation course offered modern design through modules and practice, and
      trainees both improved their existing knowledge and skills and acquired new ones
      necessary for everyday work. The coordinator emphasised the importance of the
      introduction of new teaching methods and formative assessment, the important role
      of mentors, and the involvement of Slovenian colleagues in the teaching process
      and supervision of the programme. Conclusions: The implementation of speciality
      training in FM in Montenegro was successful. Several assessment methods were used
      that can be further developed in individual structured feedback, which could
      stimulate the continual improvement of trainees' knowledge and competencies.

PMID- 29651322
TI  - Management of Frailty at Individual Level - Clinical Management: Systematic
      Literature Review.
AB  - Introduction: To deliver quality management of a frail individual, a clinician
      should understand the concept of frailty, be aware of its epidemiology and be
      able to screen for frailty and assess it when it is present, and, finally, to
      recommend successful interventions. Methodology: A systematic literature search
      was conducted in the following databases: PubMed, Cochrane, Embase, Cinahl and
      UpToDate. The criterion in selecting the literature was that articles were
      published in the period from 2002 to 2017. From 67432 initial hits, 27
      publications were selected. Results: Useful interventions to address frailty are
      supplementation of vitamin D, proper nutrition, multicomponent training, home
      based physiotherapy and comprehensive geriatric assessment, particularly when
      performed in geriatric wards. Conclusion: Comprehensive geriatric assessment is
      an effective way to decrease frailty status especially when performed in
      geriatric wards. Multicomponent physical training and multidimensional
      interventions (physical training, nutrition, vitamin D supplementation and
      cognitive training) are effective measures to reduce frailty.

PMID- 29651323
TI  - Identification of Common Genes Refers to Colorectal Carcinogenesis with Paired
      Cancer and Noncancer Samples.
AB  - Colorectal cancer is a malignant tumor which harmed human beings' health. The aim
      of this study was to explore common biomarkers associated with colorectal
      carcinogenesis in paired cancer and noncancer samples. At first, fifty-nine pairs
      of colorectal cancer and noncancer samples from three gene expression datasets
      were collected and analyzed. Then, 181 upregulation and 282 downregulation common
      differential expression genes (DEGs) were found. Next, functional annotation was
      performed in the DAVID database with the DEGs. Finally, real-time polymerase
      chain reaction (PCR) assay was conducted to verify the analyses in sixteen
      colorectal cancer and individual-matched adjacent mucosa samples. Real-time PCR
      showed that MCM2, RNASEH2A, and TOP2A were upregulated in colorectal cancer
      compared with adjacent mucosa samples (MCM2, P < 0.001; RNASEH2A, P < 0.001;
      TOP2A, P = 0.001). These suggested that 463 DEGs might contribute to colorectal
      carcinogenesis.

PMID- 29651324
TI  - Cerebellum Susceptibility to Neonatal Asphyxia: Possible Protective Effects of N
      Acetylcysteine Amide.
AB  - Background: After perinatal asphyxia, the cerebellum presents more damage than
      previously suggested. Objectives: To explore if the antioxidant N-acetylcysteine
      amide (NACA) could reduce cerebellar injury after hypoxia-reoxygenation in a
      neonatal pig model. Methods: Twenty-four newborn pigs in two intervention groups
      were exposed to 8% oxygen and hypercapnia, until base excess fell to -20 mmol/l
      or the mean arterial blood pressure declined to <20 mmHg. After hypoxia, they
      received either NACA (NACA group, n = 12) or saline (vehicle-treated group, n =
      12). One sham-operated group (n = 5) served as a control and was not subjected to
      hypoxia. Observation time after the end of hypoxia was 9.5 hours. Results: The
      intranuclear proteolytic activity in Purkinje cells of asphyxiated vehicle
      treated pigs was significantly higher than that in sham controls (p = 0.03).
      Treatment with NACA was associated with a trend to decreased intranuclear
      proteolytic activity (p = 0.08), There were significantly less mutations in the
      mtDNA of the NACA group compared with the vehicle-treated group, 2.0 * 10-4 (+/
      2.0 * 10-4) versus 4.8 * 10-5(+/-3.6 * 10-4, p < 0.05). Conclusion: We found a
      trend to lower proteolytic activity in the core of Purkinje cells and
      significantly reduced mutation rate of mtDNA in the NACA group, which may
      indicate a positive effect of NACA after neonatal hypoxia. Measuring the
      proteolytic activity in the nucleus of Purkinje cells could be used to assess the
      effect of different neuroprotective substances after perinatal asphyxia.

PMID- 29651325
TI  - The Relationship between TP53 Gene Status and Carboxylesterase 2 Expression in
      Human Colorectal Cancer.
AB  - Irinotecan (CPT-11) is an anticancer prodrug that is activated by the
      carboxylesterase CES2 and has been approved for the treatment of many types of
      solid tumors, including colorectal cancer. Recent studies with cell lines show
      that CES2 expression is regulated by the tumor suppressor protein p53. However,
      clinical evidence for this regulatory mechanism in cancer is lacking. In this
      study, we examined the relationship between TP53 gene status and CES2 expression
      in human colorectal cancer. Most colorectal cancer specimens (70%; 26 of 37)
      showed lower CES2 mRNA levels (>=1.5-fold lower) than the adjacent normal tissue,
      and only 30% (12 of 37) showed similar (<1.5-fold lower) or higher CES2 mRNA
      levels. However, TP53 gene sequencing revealed no relationship between CES2
      downregulation and TP53 mutational status. Moreover, while colorectal cancer
      cells expressing wild-type p53 exhibited p53-dependent upregulation of CES2,
      PRIMA-1MET, a drug that restores the transcriptional activity of mutant p53,
      failed to upregulate CES2 expression in cells with TP53 missense mutations. These
      results, taken together, suggest that CES2 mRNA expression is decreased in human
      colorectal cancer independently of p53.

PMID- 29651326
TI  - The Role of Serum CK18, TIMP1, and MMP-9 Levels in Predicting R0 Resection in
      Patients with Gastric Cancer.
AB  - Gastric cancer is the third most common cause of death in men and the fifth
      common cause of death in women worldwide. Currently, available advanced imaging
      modalities can predict R0 resection in most patients in the perioperative period.
      The aim of this study is to determine the role of serum CK18, MMP-9, and TIMP1
      levels in predicting R0 resection in patients with gastric cancer. Fifty
      consecutive patients scheduled for curative surgery with gastric adenocancer
      diagnosis between 2013 and 2015 were included in the study. One milliliter of
      blood was taken from the patients included in the study to examine CK18, MMP-9,
      and TIMP1. CK18, MMP-9, and TIMP1 levels were positively correlated with
      pathological N and the stage (P < 0.05). The CK18, MMP-9, and TIMP1 averages of
      those with positive clinical lymph nodes and those in clinical stage 3 were found
      to be higher than the averages of those with negative clinical lymph nodes and
      those in clinical stage 2 (P < 0.05). Although serum CK18, MMP-9, and TIMP1 preop
      measurements in patients scheduled for curative surgery due to gastric
      adenocarcinoma did not help to gain any idea of tumor resectability, we concluded
      that our study had valuable results in significantly predicting N3 stage.

PMID- 29651327
TI  - Performance of Urinary Markers for Detection of Upper Tract Urothelial Carcinoma:
      Is Upper Tract Urine More Accurate than Urine from the Bladder?
AB  - Objectives: To assess the performance of urine markers determined in urine
      samples from the bladder compared to samples collected from the upper urinary
      tract (UUT) for diagnosis of UUT urothelial carcinoma (UC). Patients and Methods:
      The study comprised 758 urine samples either collected from the bladder (n = 373)
      or UUT (n = 385). All patients underwent urethrocystoscopy and UUT imaging or
      ureterorenoscopy. Cytology, fluorescence in situ hybridization (FISH),
      immunocytology (uCyt+), and nuclear matrix protein 22 (NMP22) were performed.
      Results: UUT UC was diagnosed in 59 patients (19.1%) (UUT urine) and 27 patients
      (7.2%) (bladder-derived urine). For UUT-derived samples, sensitivities for
      cytology, FISH, NMP22, and uCyt+ were 74.6, 79.0, 100.0, and 100.0, while
      specificities were 66.6, 50.7, 5.9, and 66.7%, respectively. In bladder-derived
      samples, sensitivities were 59.3, 52.9, 62.5, and 50.0% whereas specificities
      were 82.9, 85.0, 31.3, and 69.8%. In UUT-derived samples, concomitant bladder
      cancer led to increased false-positive rates of cytology and FISH. Conclusions:
      Urine markers determined in urine collected from the UUT exhibit better
      sensitivity but lower specificity compared to markers determined in bladder
      derived urine. Concomitant or recent diagnosis of UC of the bladder can further
      influence markers determined in UUT urine.

PMID- 29651328
TI  - Serum Cytokine Profiles in Patients with Dengue Fever at the Acute Infection
      Phase.
AB  - Background: Dengue virus (DENV) is transmitted by mosquito and has been
      circulating in Guangdong, China, for over 30 years. Dengue infection causes mild
      to severe disease symptoms in human. Cytokine profiles were suggested to be
      crucial especially during the acute stage in the dengue infection. Aim: To
      determine the cytokine profiles at the acute stage in patients with primary or
      secondary dengue infection in Guangzhou city in the 2014 outbreak. Methods: We
      investigated 23 inflammatory cytokines in serum collected from dengue-infected
      patients and analyzed their correlations with their clinical indexes. Results:
      The concentrations of CXCL9, IP-10, CXCL11, IL-8, IL-10, and CCL2 in serum were
      significantly higher in the groups of DENV-infected patients during the first two
      weeks than those of control group while CCL17 and CXCL5 showed lower expression
      level in the patients. Among these cytokines, CXCL9, CCL17, and CXCL5 showed
      statistical difference between the groups of primary and secondary infections.
      The platelet count and lactate dehydrogenase were correlated with the level of
      CCL17 and MIP-1alpha/CXCL5, respectively, in the group of secondary infection.
      Conclusions: We determined the cytokine profiles in serum of the patients during
      the 2014 dengue outbreak. The expression of specific cytokines was associated
      with the secondary infection.

PMID- 29651329
TI  - Ischaemia of the medullary cone after stent-graft implantation in a patient with
      abdominal aortic aneurysm - a case study.
AB  - Preoperative visualization of the Adamkiewicz artery - the vessel which is to a
      great extent responsible for supplying blood to the medullary cone - is an
      important step which must be taken before initiating restorative procedures in
      the aorta. We present a case of a 67-year-old patient who underwent an
      intravascular stent-graft implantation procedure, due to clinical signs of
      abdominal aortic aneurysm. Routine pre-operative computed tomography examination
      failed to demonstrate the Adamkiewicz artery. On the second day after the
      surgery, as a result of unexpected clinical deterioration, an magnetic resonance
      imaging examination of the lumbar spine was carried out. Based on the magnetic
      resonance imaging images and clinical manifestations the diagnosis of ischaemia
      of the medullary cone was made. In our work we also present a deep analysis of
      the anatomy of small-sized vessels supplying blood to the spinal cord and discuss
      effective techniques which enable visualization of the Adamkiewicz artery.

PMID- 29651330
TI  - Analysis of neuroanatomical differences in mice with genetically modified
      serotonin transporters assessed by structural magnetic resonance imaging.
AB  - Background: The serotonin (5-HT) system has long been implicated in autism
      spectrum disorder (ASD) as indicated by elevated whole blood and platelet 5-HT,
      altered platelet and brain receptor and transporter binding, and genetic linkage
      and association findings. Based upon work in genetically modified mice, 5-HT is
      known to influence several aspects of brain development, but systematic
      neuroimaging studies have not previously been reported. In particular, the 5-HT
      transporter (serotonin transporter, SERT; 5-HTT) gene, Slc6a4, has been
      extensively studied. Methods: Using a 7-T MRI and deformation-based morphometry,
      we assessed neuroanatomical differences in an Slc6a4 knockout mouse on a C57BL/6
      genetic background, along with an Slc6a4 Ala56 knockin mouse on two different
      genetic backgrounds (129S and C57BL/6). Results: Individually (same sex, same
      background, same genotype), the only differences found were in the female Slc6a4
      knockout mouse; all the others had no significant differences. However, an
      analysis of variance across the whole study sample revealed a significant effect
      of Slc6a4 on the amygdala, thalamus, dorsal raphe nucleus, and lateral and
      frontal cortices. Conclusions: This work shows that an increase or decrease in
      SERT function has a significant effect on the neuroanatomy in 5-HT relevant
      regions, particularly the raphe nuclei. Notably, the Slc6a4 Ala56 knockin alone
      appears to have an insignificant, but suggestive, effect compared to the KO,
      which is consistent with Slc6a4 function. Despite the small number of 5-HT
      neurons and their localization to the brainstem, it is clear that 5-HT plays an
      important role in neuroanatomical organization.

PMID- 29651331
TI  - Operationalizing atypical gaze in toddlers with autism spectrum disorders: a
      cohesion-based approach.
AB  - Background: Multiple eye-tracking studies have highlighted the "atypical" nature
      of social attention in autism. However, it is unclear how "atypical" or "typical"
      should be quantified. Methods: We developed a method for identifying moments when
      members of a group looked at similar places (High-Cohesion Time Frames; HCTFs).
      We defined typicality as the proximity of gaze points to typically developing
      (TD) gaze points during TD HCTFs. Comparing toddlers with ASD (n = 112) to
      developmentally delayed (DD, n = 36) and TD (n = 163) toddlers during a video
      with Dyadic Bid, Sandwich-Making, Joint Attention, and Animated Toys conditions,
      we examined (a) individual typicality scores, (b) the relationship between
      typicality and symptom severity, and (c) HCTF distributions associated with each
      diagnostic group. Results: The ASD group had lower gaze typicality scores
      compared to the TD and DD groups in the Dyadic Bid and Sandwich-Making conditions
      but not during Animated Toys. The DD and TD groups did not differ in any
      condition. Correlational analyses indicated that higher typicality scores were
      associated with increased looking at pre-planned locations of the scene indexed
      by each experimental condition. In the ASD group, lower gaze typicality was
      associated with more severe autism symptoms. Examining ASD HCTFs, the gaze of
      toddlers with ASD was least cohesive during Dyadic Bid and most cohesive during
      Animated Toys. Conclusion: In contrast to non-ASD groups, toddlers with ASD show
      high cohesion during salient nonsocial events, suggesting that consistency in
      looking strategies may depend more on perceptual features. These findings are
      consequential for understanding individual differences in visual attention in ASD
      and for the design of more sensitive biomarker tasks for stratification, between
      group differentiation, and measuring response to treatment.

PMID- 29651332
TI  - STAR FORMATION AT Z = 2.481 IN THE LENSED GALAXY SDSS J1110+6459: STAR FORMATION
      DOWN TO 30 PARSEC SCALES.
AB  - We present measurements of the surface density of star formation, the star
      forming clump luminosity function, and the clump size distribution function, for
      the lensed galaxy SGAS J111020.0+645950.8 at a redshift of z =2.481. The physical
      size scales that we probe, radii r = 30-50 pc, are considerably smaller scales
      than have yet been studied at these redshifts. The star formation surface density
      we find within these small clumps is consistent with surface densities measured
      previously for other lensed galaxies at similar redshift. Twenty-two percent of
      the rest-frame ultraviolet light in this lensed galaxy arises from small clumps,
      with r <100 pc. Within the range of overlap, the clump luminosity function
      measured for this lensed galaxy is remarkably similar to those of z ~ 0 galaxies.
      In this galaxy, star-forming regions smaller than 100 pc-physical scales not
      usually resolved at these redshifts by current telescopes-are important locations
      of star formation in the distant universe. If this galaxy is representative, this
      may contradict the theoretical picture in which the critical size scale for star
      formation in the distant universe is of order 1 kiloparsec. Instead, our results
      suggest that current telescopes have not yet resolved the critical size scales of
      star-forming activity in galaxies over most of cosmic time.

PMID- 29651333
TI  - A novel organ preservation solution with efficient clearance of red blood cells
      improves kidney transplantation in a canine model.
AB  - Organ preservation solutions are designed to minimize organ damage during
      transplantation. A novel preservation solution, WMO-II, was developed to have a
      low viscosity and to improve microvasculature perfusion for kidneys. In an
      autologous canine transplantation model, kidney function and recovery were
      evaluated after organs were flushed and cold-stored with WMO-II or HTK solution,
      a perfusate currently approved for clinical use. The average number of red blood
      cells remaining in a single glomerulus after flushing with WMO-II was
      significantly reduced when compared with HTK solution. Additionally, WMO-II
      reduced the number of apoptotic bodies in stored kidneys compared to HTK treated
      tissue after 48 h of cold storage by reducing expression of Caspase-9, BiP, Chop,
      and Caspase-12. WMO-II solution reduced serum creatinine levels and serum
      potassium in kidneys stored for 48 h when compared to HTK perfusion. WMO-II
      preserves kidney function as evidenced by the reduction in serum creatinine and
      potassium during graft transplantation.

PMID- 29651335
TI  - Light-Induced Remodeling of Physically Crosslinked Hydrogels Using Near-IR
      Wavelengths.
AB  - Poly([6-bromo-7-hydroxycoumarin-4-yl]methyl methacrylate)-based triblock
      copolymers were synthesized by first preparing PMAA-PEG-PMAA triblocks using
      ATRP. 6-Bromo-4-chloromethyl-7-hydroxycoumarin was conjugated to PMAA-PEG-PMAA
      using 1,8-diazabicycloundec-7-ene (DBU). Rheological measurements were conducted
      using a HR-2 rheometer with a UV illumination accessory (TA Instruments). Single
      photon uncaging was performed as previously described.20 Two-photon uncaging was
      performed using a LSM (Zeiss) equipped with a Ti: Sapphire laser (Coherent). All
      values reported as mean +/- std. dev. unless otherwise stated. See Supporting
      Information for experimental details.

PMID- 29651334
TI  - The evaluation of risk prediction models in predicting outcomes after bariatric
      surgery: a prospective observational cohort pilot study.
AB  - Background: As the prevalence of obesity is increasing, the number of patients
      requiring surgical intervention for obesity-related illness is also rising. The
      aim of this pilot study was to explore predictors of short-term morbidity and
      longer-term poor weight loss after bariatric surgery. Methods: This was a single
      centre prospective observational cohort pilot study in patients undergoing
      bariatric surgery. We assessed the accuracy (discrimination and calibration) of
      two previously validated risk prediction models (the Physiological and Operative
      Severity Score for the enumeration of Morbidity and Mortality, POSSUM score, and
      the Obesity Surgical Mortality Risk Score, OS-MS) for postoperative outcome
      (postoperative morbidity defined using the Post Operative Morbidity Survey). We
      then tested the relationship between postoperative morbidity and longer-term
      weight loss outcome adjusting for known patient risk factors. Results: Complete
      data were collected on 197 patients who underwent surgery for obesity or obesity
      related illnesses between March 2010 and September 2013. Results showed POSSUM
      and OS-MRS were less accurate at predicting Post Operative Morbidity Survey
      (POMS)-defined morbidity on day 3 than defining prolonged length of stay due to
      poor mobility and/or POMS-defined morbidity. Having fewer than 28 days alive and
      out of hospital within 30 days of surgery was predictive of poor weight loss at 1
      year, independent of POSSUM-defined risk (odds ratio 2.6; 95% confidence interval
      1.28-5.24). Conclusions: POSSUM may be used to predict patients who will have
      prolonged postoperative LOS after bariatric surgery due to morbidity or poor
      mobility. However, independent of POSSUM score, having less than 28 days alive
      and out of hospital predicted poor weight loss outcome at 1 year. This adds to
      the literature that postoperative complications are independently associated with
      poor longer-term surgical outcomes.

PMID- 29651336
TI  - PI3K, p38 and JAK/STAT signalling in bronchial tissue from patients with asthma
      following allergen challenge.
AB  - Background: Inhaled allergen challenges are often used to evaluate novel asthma
      treatments in early phase clinical trials. Current novel therapeutic targets in
      asthma include phosphoinositide 3-kinases (PI3K) delta and gamma, p38 mitogen
      activated protein kinase (p38) and Janus kinase/Signal Transducer and Activator
      of Transcription (JAK/STAT) signalling pathways. The activation of these pathways
      following allergen exposure in atopic asthma patients it is not known. Methods:
      We collected bronchial biopsies from 11 atopic asthma patients at baseline and
      after allergen challenge to investigate biomarkers of PI3K, p38 MAPK and JAK/STAT
      activation by immunohistochemistry. Cell counts and levels of eosinophil cationic
      protein and interleukin-5 were also assessed in sputum and bronchoalvelar lavage.
      Results: Biopsies collected post-allergen had an increased percentage of
      epithelial cells expressing phospho-p38 (17.5 vs 25.6%, p = 0.04), and increased
      numbers of sub-epithelial cells expressing phospho-STAT5 (122.2 vs 540.6
      cells/mm2, p = 0.01) and the PI3K marker phospho-ribosomal protein S6 (180.7 vs
      777.3 cells/mm2,p = 0.005). Type 2 inflammation was increased in the airways post
      allergen, with elevated levels of eosinophils, interleukin-5 and eosinophil
      cationic protein. Conclusions: Future clinical trials of novel kinase inhibitors
      could use the allergen challenge model in proof of concept studies, while
      employing these biomarkers to investigate pharmacological inhibition in the
      lungs.

PMID- 29651337
TI  - Weaving the health and pharmaceutical care agenda through the themes of the
      commonwealth heads of government meeting (CHOGM), London 2018.
AB  - The biennial Commonwealth Heads of Government Meeting (CHOGM) this year is based
      around four key themes: prosperity, fairness, sustainability and security. This
      is an opportune time to consider the role of pharmacists in healthcare delivery,
      and particularly their contribution to achieving the United Nations Sustainable
      Development Goals (SDGs). As a member of the Commonwealth Health Professions
      Alliance (CHPA), the Commonwealth Pharmacists Association (CPA) has been working
      to ensure that pharmacy-related aspects of health are represented in the advocacy
      papers submitted by Civil Society. Echoing the CHPA's priorities around SDG 3
      (health) and the attainment of sustainable universal health coverage (UHC), the
      CPA has been raising the profile of key priorities for our members, including:
      addressing the shortage of healthcare workers (with an emphasis on pharmacists);
      need for access to quality medicines and medicines information; tackling anti
      microbial resistance and substandard/falsified medicines; and championing the
      role of digitalisation and partnerships. This editorial discusses how the work of
      the CPA links with the themes of CHOGM, the CPA's input into this meeting and the
      direction of travel 'Towards a Common Future' for health and pharmacy in the
      Commonwealth.

PMID- 29651338
TI  - EO-1 data quality and sensor stability with changing orbital precession at the
      end of a 16 year mission.
AB  - The Earth Observing One (EO-1) satellite has completed 16 years of Earth
      observations in early 2017. What started as a technology mission to test various
      new advancements turned into a science and application mission that extended many
      years beyond the satellite's planned life expectancy. EO-1's primary instruments
      are spectral imagers: Hyperion, the only civilian full spectrum spectrometer (430
      2400 nm) in orbit; and the Advanced Land Imager (ALI), the prototype for Landsat
      8's pushbroom imaging technology. Both Hyperion and ALI instruments have
      continued to perform well, but in February 2011 the satellite ran out of the fuel
      necessary to maintain orbit, which initiated a change in precession rate that led
      to increasingly earlier equatorial crossing times during its last five years. The
      change from EO-1's original orbit, when it was formation flying with Landsat-7 at
      a 10:01am equatorial overpass time, to earlier overpass times results in image
      acquisitions with increasing solar zenith angles (SZAs). In this study, we take
      several approaches to characterize data quality as SZAs increased. Our results
      show that for both EO-1 sensors, atmospherically corrected reflectance products
      are within 5 to 10% of mean pre-drift products. No marked trend in decreasing
      quality in ALI or Hyperion is apparent through 2016, and these data remain a high
      quality resource through the end of the mission.

PMID- 29651339
TI  - Comparison of Optical Coherence Tomography Angiography and Laser Speckle
      Flowgraphy for the Diagnosis of Normal-Tension Glaucoma.
AB  - Purpose: To compare optical coherence tomography angiography (OCT-A) and laser
      speckle flowgraphy (LSFG) for the diagnosis of normal-tension glaucoma (NTG).
      Methods: Twenty-eight eyes of 28 patients with NTG and 25 eyes of 25 normal
      subjects matched for age, refractive errors, systemic blood pressure, and central
      corneal thickness were evaluated. OCT-A was used to measure whole image vessel
      density, inside disc vessel density, and peripapillary vessel density; using
      LSFG, mean blur rate (MBR) inside the whole optic nerve head (ONH) area (MBRA),
      and MBR of the vessel area (MBRV) and tissue area (MBRT) inside the ONH, were
      determined. Receiver operating characteristic (ROC) curves and areas under the
      ROC (AUROC) were used to assess the diagnostic ability of each variable. Results:
      The AUROC for OCT-A whole image vessel density (0.950) was significantly greater
      than that for OCT-A peripapillary vessel density (0.830) and for all LSFG
      parameters (MBRA = 0.793, MBRV = 0.601, and MBRT = 0.61) (P < 0.001). The AUROC
      for OCT-A inside disc vessel density (0.931) was significantly greater than that
      for all LSFG parameters (P < 0.005). Conclusions: OCT-A vessel density had a
      higher glaucoma diagnostic ability compared to all LSFG parameters in patients
      with NTG.

PMID- 29651340
TI  - Changes in Flow Density Measured Using Optical Coherence Tomography Angiography
      after iStent Insertion in Combination with Phacoemulsification in Patients with
      Open-Angle Glaucoma.
AB  - Purpose: To evaluate changes in flow density after the implantation of a
      trabecular microbypass stent (iStent) in combination with cataract surgery.
      Methods: A total of 48 eyes of 48 patients, who underwent either cataract surgery
      alone (cataract group) or cataract surgery with implantation of two iStent inject
      devices (iStent group), were prospectively included in this study. Intraocular
      pressure (IOP) and flow density data before and after surgery were extracted and
      analyzed. Results: In the iStent group, the mean IOP was 18.2 +/- 3.3 mmHg prior
      to surgery and 13.2 +/- 2.3 at follow-up, and this difference was statistically
      significant (p < 0.001). The mean IOP in the cataract group also improved
      significantly after surgery (before: 17.1 +/- 2.4; after: 15.1 +/- 2.7 p =
      0.003). The flow density (whole en face) in the superficial and deep retinal OCT
      angiogram of the macula (superficial: p = 0.002; deep: p = 0.034) and in the ONH
      (p = 0.011) improved significantly after surgery in the iStent group. The
      differences in the cataract group were not significant. Conclusions: Flow density
      of the macula and ONH, as measured by OCTA, improved significantly after cataract
      surgery with iStent. Noninvasive quantitative analyses of flow density provide a
      new parameter, which can help for the monitoring of therapy success after
      glaucoma surgery.

PMID- 29651341
TI  - The Comparison of Regional RNFL and Fundus Vasculature by OCTA in Chinese Myopia
      Population.
AB  - Purpose: To determine the correlations between peripapillary vessel density,
      retinal nerve fibre layer (RNFL) thickness, and myopic indices at retina
      quadrants with optical coherence tomography angiography (OCTA) in Chinese.
      Methods: Fifty-six subjects with a mean spherical equivalent (MSE) of -3.63 +/-
      0.29 D were included. Peripapillary RNFL thickness and retinal vessel density in
      four sectors (superior, nasal, inferior, and temporal quadrants) were determined
      by OCTA, and correlations of the main outcomes were analyzed. Results: Negative
      correlations were found between the peripapillary RNFL thickness and axial length
      (AL) at superior (r = -0.335, P = 0.001) and inferior (r = -0.551, P < 0.001)
      quadrants. There was a significant positive correlation with spherical equivalent
      (SE) at the corresponding quadrants as well as at the nasal quadrant (r = 0.339,
      P = 0.001; r = 0.379, P < 0.001; and r = 0.209, P = 0.039, resp.). Peripapillary
      retinal vessel density was also negatively correlated with AL at the nasal
      quadrant (r = -0.392, P < 0.001), and only at the nasal quadrant, there was a
      positive correlation between the peripapillary vessel density and SE (r = 0.319,
      P = 0.001). Conclusions: The degree of myopia and elongation of AL were
      negatively correlated with peripapillary RNFL thickness at superior and inferior
      quadrants and with peripapillary retinal vessel density at the nasal quadrant.

PMID- 29651342
TI  - Factors Related to a Right-Left Difference in Visual Field Defect in the Eyes
      with Untreated Normal Tension Glaucoma.
AB  - Purpose: To investigate factors related to a right-left difference in visual
      field defect in untreated normal tension glaucoma (NTG). Methods: The medical
      records of 92 patients with untreated NTG were reviewed. Ocular blood flow was
      evaluated with laser speckle flowgraphy, and the mean blur rate (MBR) at the
      optic nerve head was analyzed. Relationships between right-left differences in
      mean deviation (MD), intraocular pressure, MBR, spherical equivalent, central
      corneal thickness, and mean ocular perfusion pressure were evaluated using
      Spearman's rank correlation coefficient. Multiple regression analysis was used to
      detect factors contributing to a right-left difference in MD. Results: The right
      left difference in MD was correlated with differences in intraocular pressure (r
      = -0.263, P = 0.011), MBR (r = 0.417, P < 0.001), and spherical equivalent (r =
      0.213, P = 0.042), but not with central corneal thickness or mean ocular
      perfusion pressure. Multiple regression analysis showed that a difference in MBR
      was the only significant contributor to a right-left difference in MD (slope
      0.047, 95% confidence interval 0.025-0.069; P < 0.001). Conclusion: In untreated
      NTG, a difference in blood flow at the optic nerve head was a significant
      contributor to a right-left difference in visual field defect.

PMID- 29651343
TI  - Through-Focus Vision Performance and Light Disturbances of 3 New Intraocular
      Lenses for Presbyopia Correction.
AB  - Purpose: To compare the through-focus visual performance in a clinical population
      of pseudophakic patients implanted with two new trifocal intraocular lenses
      (IOLs) and one extended depth of focus IOL. Methods: Prospective, nonrandomized,
      examiner-masked case series. Twenty-three patients received the FineVision(r) and
      seven patients received the PanOptixTM trifocal IOLs. Fifteen patients received
      the Symfony extended depth of focus IOL. Mean age of patients was 63 +/- 8 years.
      Through-focus visual acuity was measured from -3.00 to +1.00 D vergences.
      Contrast sensitivity was measured with and without a source of glare. Light
      disturbances were evaluated with the Light Distortion Analyzer. Results: Though
      focus evaluation showed that trifocal IOLs performed significantly better at near
      distance (33 and 40 cm), and extended depth of focus performed significantly
      better at intermediate distance (1.0 m). Contrast sensitivity function with glare
      and dysphotopsia was similar between the three IOLs and subjective response to
      questionnaire showed a significantly higher score (worse performance) for the
      extended depth of focus IOL compared to both trifocal IOLs in the bothersome
      subscale (p < 0.05). Conclusions: Trifocal IOLs grant better performance at near
      distance while extended depth of focus IOL performs better at intermediate
      distance. Objective dysphotopsia measured with the Light Distortion Analyzer is
      not reduced in extended depth of focus IOL compared to trifocal IOLs.

PMID- 29651344
TI  - Etiologic Causes and Epidemiological Characteristics of Patients with Intraocular
      Foreign Bodies: Retrospective Analysis of 1340 Cases over Ten Years.
AB  - Objective: Patients with intraocular foreign bodies were retrospectively
      analyzed. Population characteristics, pathogenic factors, and the outcomes during
      the past ten years were discussed. Design: Retrospective case series study.
      Method: Medical records of 1340 patients hospitalized in Beijing Tongren Hospital
      from January 1, 2004, to December 31, 2013, were collected. Results: Average age
      was 33.0 +/- 13.8 (1-76) years old in 1340 patients. There were more males (1270,
      94.8%) than females (70, 5.2%). Patients from outside of Beijing (82.1%, n =
      1100) prevailed. Farmers (32.1%, n = 430) and workers (22.3%, n = 299) were the
      top two affected professions. Leading two causes were splashing of foreign bodies
      (SFB) (58.6%, n = 785) and explosives (31.8%, n = 426). More males than females
      were injured by SFB (59.4% versus 44.3%, P = 0.009). Firework injury was the
      commonest (41.6% versus 3.1%-15.3%, P < 0.05) in patients under nine. The annual
      percentages in patients over 50 increased (P < 0.001) and in patients by
      explosives decreased (P = 0.027). Conclusion: Most patients in this study were
      young males from outside of Beijing and farmers. SFB accounted most for patients
      over 10 years old and fireworks for those under ten. Patients over 50 increased
      while those by explosives decreased annually over the period.

PMID- 29651345
TI  - Subthreshold Photocoagulation Using Endpoint Management in the PASCAL(r) System
      for Diffuse Diabetic Macular Edema.
AB  - We evaluated subthreshold photocoagulation using endpoint management (EPM) for
      the treatment of diabetic macular edema (DME). The study enrolled 10 eyes from 10
      patients (6 men and 4 women) with DME. The entry criteria included central
      macular thickness (CMT) >= 300 MUm and decimal visual acuity (VA) <= 0.5. The
      primary endpoints were VA (logMAR) and CMT at 6 months follow-up. Secondary
      endpoints included fundus autofluorescence, macular volume (MV), and macular
      sensitivity (MS). We used the PASCAL Streamline Yellow(r) (wavelength, 577 nm)
      system to perform grid pattern laser photocoagulation at 50% of the threshold
      (size, 100 MUm; duration, 0.015 s; spacing, 0.5; and energy, 4.5-7.8 mJ). At 6
      months posttreatment, CMT was significantly decreased, while there were no
      significant changes in macular sensitivity, mean BCVA (logMAR), or macular
      volume. Autofluorescence imaging revealed no changes after treatment in 6 of 10
      eyes. No eyes exhibited subjective symptoms of scotoma after photocoagulation.
      Optical coherence tomography showed the complete resolution of macular edema in 4
      eyes (40%) after a single treatment; MS was increased in all 4 of these eyes at 6
      months posttreatment. In conclusion, subthreshold photocoagulation using EPM is
      safe and effective for DME treatment and preserves MS. This trial is registered
      with UMIN000012401.

PMID- 29651346
TI  - Choriocapillaris Loss in Advanced Age-Related Macular Degeneration.
AB  - The purpose of this review is to summarize the current knowledge on
      choriocapillaris loss in advanced age macular degeneration (AMD). Several
      histopathological studies in animal models and human eyes had showed that the
      choriocapillaris density decreases with age. However, the role of
      choriocapillaris loss is still unclear in AMD and its advanced forms, either
      choroidal neovascularization (CNV) or geographic atrophy (GA). Some authors have
      hypothesized that choriocapillaris loss might precede overt retinal pigment
      epithelium atrophy. Others have hypothesized that deposition of complement
      complexes on and around the choriocapillaris could be related to the tissue loss
      observed in early AMD. The development of imaging modalities, such as optical
      coherence tomography angiography (OCTA), have led to a better understanding of
      underlying physiopathological mechanisms in AMD. OCTA showed atrophy of
      choriocapillaris underneath and beyond the region of photoreceptors and RPE loss,
      in agreement with previous histopathologic studies. The evolution of OCTA
      technology suggests that CNV seems to originate from regions of severe
      choriocapillaris alteration. Significant progress has been made in the
      understanding of development and progression of GA and CNV. In vivo investigation
      of the choriocapillaris using OCTA may lead to new insights related to underlying
      disease mechanisms in AMD.

PMID- 29651347
TI  - Correlation between CHA2DS2-VASc Score and Glaucoma Treatment and Prognosis.
AB  - Purpose: To find if CHA2DS2-VASc scale can accurately predict the treatment,
      prognosis, and outcome for primary open-angle glaucoma (POAG). Patients and
      methods: A survey of 250,000 patient years was taken, using the records of the
      Ophthalmology Department at Ziv Medical Center. Data was collected regarding the
      retinal nerve fiber layer (RNFL), visual field (VF), line of treatment (LOT) of
      glaucoma, and all the data needed to accurately calculate CHA2DS2-VASc score for
      each patient. Results: Sixty-seven patients were included in the statistical
      analysis. The mean age was 72.5 years. The mean CHA2DS2-VASc score was 3.27 + 
      1.7. Positive Pearson's correlation coefficients were found for LOT and CHA2DS2
      VASc score, 0.35, and for RNFL grade and CHA2DS2-VASc score, 0.37. The
      correlation was negative for RNFL width and CHA2DS2-VASc score, -0.35.
      Conclusions: CHA2DS2-VASc score was shown to be correlated with glaucoma. This
      correlation was manifested positively by the LOT needed to stop glaucoma
      progression, with higher CHA2DS2-VASc scores correlated with more aggressive
      treatment. Since glaucoma is a disease with a progressing nature, it is important
      to treat patients aggressively on one hand, while offering the most benign
      treatment as possible on the other hand. Modification of the CHA2DS2-VASc score
      could achieve an even higher correlation.

PMID- 29651348
TI  - DNA Methylation Status of the Interspersed Repetitive Sequences for LINE-1, Alu,
      HERV-E, and HERV-K in Trabeculectomy Specimens from Glaucoma Eyes.
AB  - Background/Aims: Epigenetic mechanisms via DNA methylation may be related to
      glaucoma pathogenesis. This study aimed to determine the global DNA methylation
      level of the trabeculectomy specimens among patients with different types of
      glaucoma and normal subjects. Methods: Trabeculectomy sections from 16 primary
      open-angle glaucoma (POAG), 12 primary angle-closure glaucoma (PACG), 16
      secondary glaucoma patients, and 10 normal controls were assessed for DNA
      methylation using combined-bisulfite restriction analysis. The percentage of
      global methylation level of the interspersed repetitive sequences for LINE-1,
      Alu, HERV-E, and HERV-K were compared between the 4 groups. Results: There were
      no significant differences in the methylation for LINE-1 and HERV-E between
      patients and normal controls. For the Alu marker, the methylation was
      significantly lower in all types of glaucoma patients compared to controls (POAG
      52.19% versus control 52.83%, p = 0.021; PACG 51.50% versus control, p = 0.005;
      secondary glaucoma 51.95% versus control, p = 0.014), whereas the methylation
      level of HERV-K was statistically higher in POAG patients compared to controls
      (POAG 49.22% versus control 48.09%, p = 0.017). Conclusions: The trabeculectomy
      sections had relative DNA hypomethylation of Alu in all glaucoma subtypes and
      relative DNA hypermethylation of HERV-K in POAG patients. These methylation
      changes may lead to the fibrotic phenotype in the trabecular meshwork.

PMID- 29651349
TI  - Listeria monocytogenes Infection in Hairy Cell Leukemia: A Case Report and
      Literature Review.
AB  - Listeria monocytogenes infections have been described in patients with diverse
      types of malignancy, especially leukemia. We report the case of a 65-year-old man
      with previously untreated hairy cell leukemia characterized by CD5 positivity and
      trisomy 12 (3% of blood lymphocytes) who developed bacteremia due to L.
      monocytogenes serotype 1/2b. We summarize clinical features and treatment of this
      patient and five previously reported patients with hairy cell leukemia who also
      had L. monocytogenes infections. All six patients were men. Their mean age at
      infection diagnosis was 70 y. Three men had undergone splenectomy 4-11 y before
      they developed L. monocytogenes infection. The central nervous system was the
      primary site of infection in four men. Bacteremia alone occurred in two other
      men. At diagnosis of infection, one man was receiving antileukemia chemotherapy
      and another man was receiving treatment for Kaposi's sarcoma. Two other patients
      had other comorbid conditions. All six men recovered from their infections.

PMID- 29651350
TI  - Dural Plasmacytoma with Meningeal Myelomatosis in a Patient with Multiple
      Myeloma.
AB  - Here, we describe the case of a 66-year-old male diagnosed with multiple myeloma
      who presented with generalized tonic-clonic seizures. Magnetic resonance imaging
      demonstrated a right solid extra-axial parieto-occipital lesion with typical
      characteristics of meningeal myelomatosis. Biopsy was performed, which diagnosed
      a dural plasmacytoma. Because of this, we started concomitant therapy with
      radiotherapy and lenalidomide, but the patient has a poor response to treatment
      and died few weeks after its initiation. Myelomatous involvement of the dura
      mater is a rare occurrence, given that only few cases were reported in the
      English literature. This presentation confers an ominous prognosis and must be a
      suspect diagnosis in patients diagnosed with multiple myeloma presenting
      neurological symptoms.

PMID- 29651351
TI  - Acquired von Willebrand Disease Associated with Mantle Cell Lymphoma.
AB  - We present a rare case of acquired von Willebrand syndrome (AVWS) caused by a
      mantle cell lymphoma. A 61-year-old male suffered from recurrent bleeding
      symptoms since a few months. Initially, physical examination was normal. von
      Willebrand factor antigen (VWF:Ag) level and factor VIII activity (FVIII:C) were
      low (0.31 IU/ml and 0.43 IU/ml, resp.). Ristocetin cofactor activity (VWF:RCo)
      was 0.09 IU/ml, and collagen binding activity (VWF:CB) was 0.10 IU/ml.
      VWF:RCo/VWF:Ag ratio was 0.29, and RIPA value was normal. Highest molecular
      weight VWF multimers were absent. A diagnosis of von Willebrand Disease (VWD)
      type 2A was made. However, no genetic mutation was found. No inhibitory
      antibodies against VWF or factor VIII were detected. A few months later,
      cervical, axillary, and inguinal lymphadenopathy was found on physical
      examination. A CT scan confirmed multiple enlarged lymph nodes, and a clonal B
      cell population matching a mantle cell lymphoma was detected in the bone marrow.
      Chemoimmunotherapy resulted in a very good partial remission and concomitantly in
      a rapid decrease of bleeding problems and complete normalization of FVIII:C and
      VWF:Ag. The diagnosis of AVWS cannot be rejected by negative mixing studies due
      to difficulties in the detection of autoantibodies and because of a highly
      heterogeneous pathogenesis of AVWS. When the suspicion of AVWS is high, an
      extensive investigation should be performed to find the underlying cause.

PMID- 29651352
TI  - Prolonged Survival of Acute Lymphoblastic Leukemia with Intrathecal Treatments
      for Isolated Central Nervous System Relapse.
AB  - Acute lymphoblastic leukemia is commonly cured when diagnosed in the pediatric
      population. It portends a poorer prognosis if present in adult patients. Although
      adults frequently achieve complete remission, relapse rates are substantial,
      particularly among the elderly and high-risk populations. In the absence of
      prophylactic intrathecal chemotherapy, more than half of patients may develop CNS
      involvement or relapse, which is associated with significant risk for systemic
      illness. This report describes a patient with acute lymphoblastic leukemia with
      repeated isolated CNS relapses. This case should remind clinicians that isolated
      CNS disease in the absence of systemic recurrence could successfully respond to
      intrathecal therapy and offer patients a favorable quality of life.

PMID- 29651353
TI  - A Rare Case of Systemic AL Amyloidosis with Muscle Involvement: A Misleading
      Diagnosis.
AB  - Muscle involvement in AL amyloidosis is a rare condition, and the diagnosis of
      amyloid myopathy is often delayed and underdiagnosed. Amyloid myopathy may be the
      initial manifestation and may precede the diagnosis of systemic AL amyloidosis.
      Here, we report the case of a 73-year-old man who was referred to our center for
      a monoclonal gammopathy of undetermined significance (MGUS) diagnosed since 1999.
      He reported a progressive weakness of proximal muscles of the legs with onset six
      months previously. Muscle biopsy showed mild histopathology featuring alterations
      of nonspecific type with a mixed myopathic and neurogenic involvement, and the
      diagnostic turning point was the demonstration of characteristic green
      birefringence under cross-polarized light following Congo red staining of
      perimysial vessels. Transmission electron microscopy (TEM) confirmed amyloid
      fibrils around perimysial vessels associated with collagen fibrils. A stepwise
      approach to diagnosis and staging of this disorder is critical and involves
      confirmation of amyloid deposition, identification of the fibril type, assessment
      of underlying amyloidogenic disorder, and evaluation of the extent and severity
      of amyloidotic organ involvement.

PMID- 29651354
TI  - Evolution of Choroidal Neovascularization due to Presumed Ocular Histoplasmosis
      Syndrome on Multimodal Imaging including Optical Coherence Tomography
      Angiography.
AB  - A 37-year-old Caucasian woman presented with acute decrease in central vision in
      her right eye and was found to have subfoveal choroidal neovascularization (CNV)
      due to presumed ocular histoplasmosis syndrome (POHS). Her visual acuity improved
      from 20/70 to 20/20 at her 6-month follow-up, after 3 consecutive monthly
      intravitreal bevacizumab injections were initiated at her first visit. Although
      no CNV activity was seen on fluorescein angiography (FA) or spectral-domain
      optical coherence tomography (SD-OCT) at her 2-month, 4-month, and 6-month follow
      up visits, persistent flow in the CNV lesion was detected on optical coherence
      tomography angiography (OCTA). OCTA shows persistent vascular flow as well as
      changes in vascular flow in CNV lesions associated with POHS, indicating the
      continued presence of patent vessels and changes in these CNV lesions, even when
      traditional imaging of the lesion with OCT and FA indicates stability of the
      lesion with no disease activity. Additional cases with longitudinal follow-up are
      needed to assess how OCTA should be incorporated into clinical practice.

PMID- 29651355
TI  - Cutaneous Adnexal Cylindroma of Breast: Epithelial Immunoreactivities for GATA-3,
      Mammaglobin, and E-Cadherin Do Not Equate to a Mammary Ductal Neoplasm.
AB  - Cylindromas are benign epithelial neoplasms derived from cutaneous eccrine
      adnexal structures. These tumors are most commonly encountered on the head, neck,
      and scalp of older women. In rare instances, solitary cylindromas may arise at
      other body sites. In the current case, a cylindroma of the skin of the breast was
      diagnosed by complete excision. Immunohistochemical studies confirmed the tumor
      cells to be immunoreactive with cytokeratin AE1/3, cytokeratin 5/6, cytokeratin
      7, p63, and SOX10. The neoplastic cells were also noted to be immunoreactive with
      markers typically expected to be positive in ductal epithelium of the breast
      including GATA3, mammaglobin, and E-cadherin. The case emphasizes the importance
      of correlating clinical setting, imaging studies, patient history, and careful
      microscopic evaluation in arriving at an accurate diagnosis. This case also
      illustrates the point that not all "breast" tumors that are confirmed to be
      positive for GATA3, mammaglobin, and E-cadherin are derived from mammary ducts.

PMID- 29651356
TI  - Cerebellar Medulloblastoma in Middle-to-Late Adulthood.
AB  - Medulloblastoma is a malignant brain tumor that is typically seen in children. It
      is classified as an embryonal tumor, classically located within the posterior
      fossa. When it involves the fourth ventricle, the patient commonly presents with
      signs and symptoms of raised intracranial pressure secondary to obstructive
      hydrocephalus. It is exceedingly rare for Medulloblastoma to occur in middle and
      late adulthood. In this paper, we present a case of a 51-year-old man who
      presented with a posterior fossa mass that was diagnosed later as
      Medulloblastoma.

PMID- 29651357
TI  - Respiratory Epithelial Orbital Cyst: A Case Report and Literature Review.
AB  - A 44-year-old male with schizophrenia presented with progressive right proptosis
      for one year and conjunctivitis for two months. An orbital cyst was seen in the
      superotemporal region on computerized tomography and was surgically removed.
      There was no history or radiological signs of paranasal sinus disease or previous
      trauma. Histopathologic evaluation revealed a cyst lined with respiratory
      epithelium. Respiratory choristomatous cysts of the orbit are considered rare in
      both pediatric and adult patients. We review the literature of respiratory
      orbital cysts and conclude that they tend to present in adults and should be
      considered in the differential diagnoses of orbital cysts.

PMID- 29651358
TI  - Pilot Study of Intra-Aortic Balloon Occlusion to Limit Morbidity in Patients with
      Adherent Placentation Undergoing Cesarean Hysterectomy.
AB  - Objective  We study whether using an intra-aortic balloon (IAB) during cesarean
      hysterectomy decreases delivery morbidity in patients with suspected morbidly
      adherent placentation. Study Design  This is a retrospective cohort study of
      deliveries complicated by suspected abnormal placentation between 2009 and 2016
      comparing maternal and neonatal outcomes with an IAB placed prior to cesarean
      hysterectomy versus no IAB. The primary outcome included quantified blood loss
      (QBL). Results  Thirty-five cases were reviewed, 16 with IAB and 19 without IAB.
      No difference was seen in median QBL between the two groups (1,351 vs. 1,397 mL;
      p  = 0.90). There were no significant differences in overall surgical
      complications (19% IAB, 21% no IAB; p  = 0.86), bladder complications (12 vs.
      21%; p  = 0.66), intensive care unit admissions (12 vs. 26%; p  = 0.41), surgical
      duration (2.9 vs. 2.8 hour; p  = 0.83), or blood transfusions (median 2 vs. 2; p 
      = 0.27) between the two groups. There was one groin hematoma at the balloon site
      that was managed conservatively. There were no complications involving thrombosis
      or limb ischemia in the IAB group. Conclusion  While we did not detect
      statistically significant differences, larger studies may be warranted given the
      potential for extreme morbidity in these cases. This study highlights the
      potential use of an IAB in the management of these cases.

PMID- 29651359
TI  - Preclinical Labor-and-Delivery Shadowing: The Impact on Medical Students'
      Perceptions of Obstetrics and Gynecology.
AB  - Objective  We sought to determine the impact of preclinical exposure (shadowing)
      to labor and delivery (L&D) on medical students' perceptions of obstetrics and
      gynecology (OB/GYN). Study Design  We administered a written survey to rising
      third-year medical students at a single center prior to any clerkship. We
      described motivation/deterrents for shadowing among students, and
      experiences/perceptions of those students who shadowed. Results  In total,
      119/136 (86%) students completed the survey. Of those, 29% participated in
      shadowing on L&D. Participating students were more likely to be female (79 vs.
      21%; p  < 0.01) and in their first year (85%). Ninety-one percent participated
      because they wanted more exposure to OB/GYN, whereas only 53% they were
      interested in OB/GYN. Students who did not shadow indicated not having enough
      time as the main reason. After participation, 82% had more perspective on OB/GYN
      than prior to shadowing. Ninety-seven percent felt that the experience was
      worthwhile; 62% stated based on their experience that they were likely to
      consider a career in OB/GYN. All students who participated stated that they would
      opt to shadow again if given the opportunity. Conclusion  Students who have L&D
      shadowing exposure report very positive experiences and express desire for
      increased opportunities. OB/GYN departments may consider increasing availability
      of L&D shadowing opportunities for preclinical medical students.

PMID- 29651361
TI  - Volumetric Measurement of Subretinal Blebs Using Microscope-Integrated Optical
      Coherence Tomography.
AB  - Purpose: We advance studies of subretinal treatments by developing a microscope
      integrated optical coherence tomography (MIOCT) image-based method for measuring
      the volume of therapeutics delivered into the subretinal space. Methods: A MIOCT
      image-based volume measurement method was developed and assessed for accuracy and
      reproducibility by imaging an object of known size in model eyes. This method
      then was applied to subretinal blebs created by injection of diluted
      triamcinolone. Bleb volumes obtained from MIOCT were compared to the intended
      injection volume and the surgeon's estimation of leakage. Results: Validation of
      the image-based volume measurement method showed accuracy to +/-1.0 MUL (6.0% of
      measured volume) with no statistically significant variation under different
      imaging settings. When this method was applied to subretinal blebs, four of 11
      blebs without surgeon-observed leakage yielded a mean volume of 32 +/- 12.5 MUL,
      in contrast to the intended 50 MUL volume injected from the delivery device. This
      constituted a mean difference of -18 MUL (mean percent error, 36 +/- 25%). For
      all 11 blebs, the surgeon's estimations of leakage were significantly different
      from and showed no correlation with the volume loss based on image-based volume
      measurements (P < 0.001, paired t-test; intraclass correlation = 0). Conclusions:
      We validated an accurate and reproducible method for measuring subretinal volumes
      using MIOCT. Use of this method revealed that the intended volume might not be
      delivered into the subretinal space. MIOCT can allow for accurate assessment of
      subretinal dose delivered, which may have therapeutic implications in evaluating
      the efficacy and toxicity of subretinal therapies. Translational Relevance: Use
      of MIOCT can provide feedback on the accuracy of subretinal injection volumes
      delivered.

PMID- 29651362
TI  - Permanent Unilateral Hearing Loss (UHL) and Childhood Development.
AB  - Purpose of Review: The aim of this study is to summarize the consequences of
      permanent unilateral hearing loss (UHL) on the development of children as
      documented in the recent literature. Recent Findings: Congenital and early
      identified UHL places young children at risk for delays in speech-language
      development. School-aged children with UHL score lower on standardized tests of
      language and cognition and need increased assistance in school for educational
      and behavioral issues than siblings with normal hearing, and report lower hearing
      related quality of life, similar to children with bilateral hearing loss (HL).
      Early intervention, including use of hearing amplification devices, might
      ameliorate some of those affects. For a child with mild to severe UHL at
      presentation, the risk of progression of HL in the worse-hearing ear may be as
      high as 40%, and the risk of progression to bilateral HL approaches 20%. Summary:
      Although UHL can adversely affect the development of children, how to mitigate
      those effects requires investigation.

PMID- 29651360
TI  - Phosphatase of regenerating liver-3 (PRL-3) is overexpressed in classical Hodgkin
      lymphoma and promotes survival and migration.
AB  - Background: Phosphatase of regenerating liver-3 (PRL-3) is implicated in
      oncogenesis of hematological and solid cancers. PRL-3 expression increases
      metastatic potential, invasiveness and is associated with poor prognosis. With
      this study, we aimed to show a possible oncogenic role of PRL-3 in classical
      Hodgkin lymphoma (cHL). Methods: PRL-3 expression was measured in 25 cHL patients
      by immunohistochemistry and gene expression was analyzed from microdissected
      malignant cells. We knocked down PRL-3 in the cHL cell lines L1236 and HDLM2 and
      used small molecular inhibitors against PRL-3 to investigate proliferation,
      migration and cytokine production. Results: PRL-3 protein was expressed in 16% of
      patient samples. In three different gene expression datasets, PRL-3 was
      significantly overexpressed compared to normal controls. PRL-3 knockdown reduced
      proliferation, viability and Mcl-1 expression in L1236, but not in HDLM2 cells.
      Thienopyridone, a small molecule inhibitor of PRL-3, reduced proliferation of
      both L1236 and HDLM2. PRL-3 affected IL-13 secretion and enhanced STAT6
      signaling. IL-13 stimulation partially rescued proliferation in L1236 cells after
      knockdown of PRL-3. PRL-3 knockdown reduced migration in both L1236 and HDLM2
      cells. Conclusion: PRL-3 was overexpressed in a subset of cHL patients.
      Inhibition of PRL-3 increased IL-13 cytokine production and reduced migration,
      proliferation and viability. The effects could be mediated through regulation of
      the anti-apoptotic molecule Mcl-1 and a feedback loop of IL-13 mediated
      activation of STAT6. This point to a role for PRL-3 in the pathogenesis of
      Hodgkin lymphoma, and PRL-3 could be a possible new drug target.

PMID- 29651364
TI  - Precision of EM Simulation Based Wireless Location Estimation in Multi-Sensor
      Capsule Endoscopy.
AB  - In this paper, we compute and examine two-way localization limits for an RF
      endoscopy pill as it passes through an individuals gastrointestinal (GI) tract.
      We obtain finite-difference time-domain and finite element method-based
      simulation results position assessment employing time of arrival (TOA). By means
      of a 3-D human body representation from a full-wave simulation software and
      lognormal models for TOA propagation from implant organs to body surface, we
      calculate bounds on location estimators in three digestive organs: stomach, small
      intestine, and large intestine. We present an investigation of the causes
      influencing localization precision, consisting of a range of organ properties;
      peripheral sensor array arrangements, number of pills in cooperation, and the
      random variations in transmit power of sensor nodes. We also perform a
      localization precision investigation for the situation where the transmission
      signal of the antenna is arbitrary with a known probability distribution. The
      computational solver outcome shows that the number of receiver antennas on the
      exterior of the body has higher impact on the precision of the location than the
      amount of capsules in collaboration within the GI region. The large intestine is
      influenced the most by the transmitter power probability distribution.

PMID- 29651363
TI  - Surgical Management of the Drooling Child.
AB  - Purpose of Review: Our goal is to present the most up-to-date options in the
      surgical management of drooling in the paediatric population. While the clinical
      assessment of the drooling child and conservative management options are
      discussed, this review focuses on the most recent evidence for surgical
      interventions to treat drooling in children. Recent Findings: In terms of
      advances in the management of drooling, further experience and outcomes with the
      use of botulinum toxin injections is discussed. Moreover, the latest evidence
      base for salivary duct ligation and relocation procedures are presented. Finally,
      the trans-oral approach to submandibular gland excision for the management of
      drooling may gain popularity through the aim of reducing surgical morbidity.
      Summary: The drooling child should be managed with an evidence-based stepwise
      approach delivered by a multidisciplinary team (MDT). Children with normal
      neurological development should be treated conservatively through parental
      reassurance. There are numerous interventions available for the drooling child
      with impaired neuromuscular development. When conservative measures fail,
      treatment options include botulinum toxin injections and surgical procedures such
      as salivary duct ligation, salivary duct relocation and salivary gland excision.
      Management must be targeted to the individual needs and comorbidities of the
      child to maximise treatment outcomes.

PMID- 29651365
TI  - Mastication Evaluation With Unsupervised Learning: Using an Inertial Sensor-Based
      System.
AB  - There is a direct relationship between the prevalence of musculoskeletal
      disorders of the temporomandibular joint and orofacial disorders. A well
      elaborated analysis of the jaw movements provides relevant information for
      healthcare professionals to conclude their diagnosis. Different approaches have
      been explored to track jaw movements such that the mastication analysis is
      getting less subjective; however, all methods are still highly subjective, and
      the quality of the assessments depends much on the experience of the health
      professional. In this paper, an accurate and non-invasive method based on a
      commercial low-cost inertial sensor (MPU6050) to measure jaw movements is
      proposed. The jaw-movement feature values are compared to the obtained with
      clinical analysis, showing no statistically significant difference between both
      methods. Moreover, We propose to use unsupervised paradigm approaches to cluster
      mastication patterns of healthy subjects and simulated patients with facial
      trauma. Two techniques were used in this paper to instantiate the method:
      Kohonen's Self-Organizing Maps and K-Means Clustering. Both algorithms have
      excellent performances to process jaw-movements data, showing encouraging results
      and potential to bring a full assessment of the masticatory function. The
      proposed method can be applied in real-time providing relevant dynamic
      information for health-care professionals.

PMID- 29651366
TI  - Height and Weight Estimation From Anthropometric Measurements Using Machine
      Learning Regressions.
AB  - Height and weight are measurements explored to tracking nutritional diseases,
      energy expenditure, clinical conditions, drug dosages, and infusion rates. Many
      patients are not ambulant or may be unable to communicate, and a sequence of
      these factors may not allow accurate estimation or measurements; in those cases,
      it can be estimated approximately by anthropometric means. Different groups have
      proposed different linear or non-linear equations which coefficients are obtained
      by using single or multiple linear regressions. In this paper, we present a
      complete study of the application of different learning models to estimate height
      and weight from anthropometric measurements: support vector regression, Gaussian
      process, and artificial neural networks. The predicted values are significantly
      more accurate than that obtained with conventional linear regressions. In all the
      cases, the predictions are non-sensitive to ethnicity, and to gender, if more
      than two anthropometric parameters are analyzed. The learning model analysis
      creates new opportunities for anthropometric applications in industry, textile
      technology, security, and health care.

PMID- 29651367
TI  - "Lazarus Response" to Olaparib in a Virtually Chemonaive Breast Cancer Patient
      Carrying Gross BRCA2 Gene Deletion.
AB  - This report describes an estrogen receptor-positive breast cancer patient, who
      relapsed at two and a half years after the completion of adjuvant chemotherapy
      while being on the aromatase inhibition. Based on the clinical evidence for
      potential sensitivity of the tumor to hormone ablation, everolimus was added to
      continuing exemestane treatment. Oral chemotherapy was administered at further
      disease progression, however, it lasted only for 10 days due to rapidly
      deteriorating condition of the patient. BRCA test was performed just before the
      failure of endocrine therapy and revealed a gross deletion within BRCA2 gene.
      Since the patient already developed contraindications to the standard
      chemotherapy, olaparib (300 mg twice a day) was given as a last hope option. The
      patient demonstrated a "Lazarus response": the performance status and the results
      of the biochemical tests went back to the norm within first two weeks of
      treatment. Positron emission tomography-computed tomography (PET-CT) was
      performed at one month after the start of olaparib therapy, and revealed complete
      metabolic response for all multiple metastatic lesions located in the liver,
      bones, small pelvis, lungs, mediastinum, retroperitoneum, etc. Cytotoxic therapy
      and poly ADP-ribose polymerase (PARP) inhibitors are known to have virtually
      identical mechanisms of tumor escape from the treatment, which are confined to
      the restoration of BRCA proficiency within cancer cells. The pronounced tumor
      response to the treatment in this patient can be attributed to the lack of recent
      exposure to standard cytotoxic treatment as well as to the inability of tumors
      with gross BRCA rearrangements to restore BRCA function via secondary mutation.
      This observation calls for comprehensive evaluation of PARP inhibitors in
      chemonaive patients with hereditary cancer.

PMID- 29651368
TI  - Synchronous Pulmonary Neoplasms: A Chance Occurrence or is There More Than Meets
      the Eye?
AB  - Primary bronchus-associated lymphoid tissue (BALT) lymphoma comprises 5% of non
      Hodgkin's lymphoma (NHL) and usually has an indolent course. Synchronous primary
      lung cancers with BALT lymphoma are seldom seen in patients with adenocarcinoma
      of the lung. Synchronous squamous cell carcinoma (SCC) and BALT lymphoma is an
      extremely rare occurrence. We report an unusual case of stage 4 BALT lymphoma
      requiring treatment that revealed an underlying ipsilateral mass causing a
      diagnostic dilemma. An 84-year-old female with a history of systemic lupus
      erythematosus, deep vein thrombosis, and thrombotic microangiopathy presented to
      the hospital with cough and dyspnea on exertion. A chest X-ray revealed right
      hemi-thorax opacification and computed tomography (CT) of the chest showed a
      large right effusion and a soft tissue density extending into the proximal right
      bronchus. She required repeated thoracentesis until the pleural fluid analysis
      showed the presence of small lymphocytes and bronchial washings revealed an
      abnormal B cell population consistent with extranodal marginal zone lymphoma. The
      patient received four cycles of bendamustine and rituximab resulting in near
      complete resolution of the effusion. Four months from diagnosis, imaging showed
      an increase in the size of the soft tissue density with pathologic
      fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET). A CT
      guided biopsy was consistent with squamous cell lung cancer (SCLC) and
      radiotherapy was started for clinical stage 2 disease since the patient was not a
      surgical candidate. BALT lymphoma is a low-grade malignancy classified as
      extranodal marginal zone lymphoma with a five-year survival rate of over 80%.
      Several cases of synchronous lung adenocarcinoma and BALT lymphoma have been
      described. However, our case is among the rare few cases of synchronous
      occurrence of SCLC with BALT lymphoma. This report highlights the challenges
      associated with establishing an accurate and timely diagnosis.

PMID- 29651369
TI  - Unusual Relapse of Chronic Lymphocytic Leukemia After Remission.
AB  - Chronic lymphocytic leukemia (CLL) is the most prevalent leukemia with over
      20,000 estimated cases in 2017. Leukemic involvement of the nervous system from
      CLL causing neurologic symptoms is reported in only about one percent of
      patients. Unfortunately, there is no current standard therapy for the treatment
      of CLL leptomeningeal disease. In this case, we discuss an unusual presentation
      of CLL leptomeningeal disease misdiagnosed as chronic rebound headache. A 61-year
      old female was diagnosed with Rai stage I CLL in 2002. She presented at that time
      with peripheral blood lymphocytosis and subsequent flow cytometry revealed a
      mature B cell population consistent with CLL. She was monitored clinically as
      there were no indications for therapy. In 2006, she developed B symptoms along
      with hemolytic anemia refractory to steroids and was initiated on chemotherapy
      with fludarabine, cyclophosphamide, and rituximab (FCR). She had a complete
      response after six cycles. The patient was in her usual state of health until
      2016, when she complained of chronic headaches. She took acetaminophen and
      ibuprofen regularly and was diagnosed with rebound headaches by neurology. These
      symptoms progressed and the patient developed encephalopathy requiring inpatient
      admission. Magnetic resonance imaging (MRI) revealed abnormal enhancement in the
      cerebellar peduncles and dentate nuclei symmetrically; a lumbar puncture
      performed revealed evidence of CLL consistent with leptomeningeal disease.
      Therapy was started with oral ibrutinib at 560 mg daily for better central
      nervous system (CNS) penetration. After three months of therapy, she had complete
      resolution of symptoms and MRI abnormalities. Leptomeningeal disease is a rare
      complication of CLL that clinicians should be aware of and ibrutinib can be an
      effective, tolerable therapy for this debilitating disease.

PMID- 29651370
TI  - Effect of the Specific Carbohydrate Diet on the Microbiome of a Primary
      Sclerosing Cholangitis and Ulcerative Colitis Patient.
AB  - A 20-year-old female was diagnosed with ulcerative colitis (UC) at age 14 and
      primary sclerosing cholangitis (PSC) at age 16. The PSC was successfully treated
      with high doses of oral vancomycin; however, the UC was more difficult to manage.
      After many drug treatments failed to treat the UC, the patient began following
      the specific carbohydrate diet (SCD). This report documents fecal microbiome
      changes resulting from following the SCD for two weeks. The DNA extracted from
      fecal samples was subjected to 16S rRNA gene sequencing to quantify bacterial
      species abundance. Not only were substantial changes in the fecal bacterial
      composition detectable within two weeks, but all UC symptoms were also controlled
      as early as one week following the start of the diet. The patient's fecal
      microbiota was dramatically different from those of three healthy control
      subjects and showed remarkable loss of bacterial diversity in terms of species
      richness, evenness, and overall diversity measures. Other specific changes in
      bacterial composition included an increase in Enterobacteriaceae, including
      Escherichia and Enterobacter species. A two- to three-fold decrease was observed
      in the prevalence of the most dominant fecal bacterial species, Fusobacterium
      ulcerans, after two weeks on the SCD. Overall species diversity and evenness
      increased to levels near the controls, although species richness remained low.
      These findings provide information on the fecal bacteria from a patient with PSC
      and UC, following prolonged oral vancomycin treatment, and identifies a
      potentially specific microbial effect for the SCD.

PMID- 29651371
TI  - Tenecteplase versus Alteplase for the Management of Acute Ischemic Stroke in a
      Low-income Country-Nepal: Cost, Efficacy, and Safety.
AB  - Intravenous alteplase is the only approved treatment for acute ischemic stroke.
      Tenecteplase, a genetically engineered, mutant tissue plasminogen activator, is
      an alternative thrombolytic agent. The economic feasibility of stroke treatment
      has been a matter of huge debate and discussion thus far. The use of
      thrombolytics for the management of ischemic stroke has recently begun in Nepal.
      In low-income countries like Nepal, where the per capita income falls at just
      $691.7 and 25.2% of the population are under the poverty line, stroke patients
      cannot meet treatment expenses. Tenecteplase is easily available (for the
      management of acute coronary syndrome) in tertiary-level hospitals of Nepal and
      the price quote of tenecteplase ($450) is half the price of alteplase ($1000). In
      emergency cases, sometimes, the cost of alteplase can be greater than the patient
      can afford and they can't undergo thrombolysis even after arriving on time.
      However, evidence exists that supports the use of other alternatives
      (tenecteplase), which are also effective in the management of acute ischemic
      stroke. In this article, we examined current evidence for the efficacy and safety
      of tenecteplase when compared to alteplase. This review will make neurologists in
      Nepal familiar with the efficacy and safety of tenecteplase in comparison with
      alteplase since it is common for patients to not be able to afford the expensive
      alteplase, which makes guideline-based practice impossible some times.

PMID- 29651372
TI  - Epidemiology and Characteristics of Cervical Spine Injury in Patients Presenting
      to a Regional Emergency Department.
AB  - Purpose This study aims to establish the demographics and characteristics of
      patients with cervical spine injury (CSI) in an Irish cohort presenting to a
      regional emergency department. Methods We performed a retrospective analysis of
      the medical records of patients who underwent cervical spine computed tomography
      (CT) scans following trauma from January 2013 to July 2016. We looked at the
      mechanism of injury, mode of arrival to the emergency department, triage
      category, correlation between examination, and site of CSI and neurological
      status. Results Over the study period, 808 patients underwent CT scans of the
      cervical spine for potential CSI. The incidence of CSI in our cohort was 9.4% (n
      = 76). Approximately 70% (n = 53) were men. Falls (53%) and motor vehicle
      accidents (29%) were noted to be the more common mechanisms of injury in this
      cohort. The C2 region was the most common location for CSI. Only 7% (n = 5) of
      patients had documented neurology. Conclusion This study demonstrates the
      epidemiology and characteristics of CSI presenting in an Irish cohort. The
      incidence of CSI was found to be 9.4% with a male preponderance and falls being
      the most common cause of trauma.

PMID- 29651373
TI  - Using MODIS Cloud Regimes to Sort Diagnostic Signals of Aerosol-Cloud
      Precipitation Interactions.
AB  - Coincident multi-year measurements of aerosol, cloud, precipitation and radiation
      at near-global scales are analyzed to diagnose their apparent relationships as
      suggestive of interactions previously proposed based on theoretical,
      observational, and model constructs. Specifically, we examine whether differences
      in aerosol loading in separate observations go along with consistently different
      precipitation, cloud properties, and cloud radiative effects. Our analysis uses a
      cloud regime (CR) framework to dissect and sort the results. The CRs come from
      the Moderate Resolution Imaging Spectroradiometer (MODIS) sensor and are defined
      as distinct groups of cloud systems with similar co-variations of cloud top
      pressure and cloud optical thickness. Aerosol optical depth used as proxy for
      aerosol loading comes from two sources, MODIS observations, and the MERRA-2 re
      analysis, and its variability is defined with respect to local seasonal
      climatologies. The choice of aerosol dataset impacts our results substantially.
      We also find that the responses of the marine and continental component of a CR
      are frequently quite disparate. Overall, CRs dominated by warm clouds tend to
      exhibit less ambiguous signals, but also have more uncertainty with regard to
      precipitation changes. Finally, we find weak, but occasionally systematic co
      variations of select meteorological indicators and aerosol, which serves as a
      sober reminder that ascribing changes in cloud and cloud-affected variables
      solely to aerosol variations is precarious.

PMID- 29651374
TI  - Biochemical events during somatic embryogenesis in Coffea arabica L.
AB  - Several biochemical components associated with different stages of somatic
      embryogenesis in coffee (Coffea arabica L.) are investigated using foliar
      explants. Soluble sugar, starch, free amino acids and total proteins were
      extracted and quantified at different stages of somatic embryogenesis, such as
      foliar segments (initial explants), primary calluses, embryogenic calluses,
      globular embryos, torpedoes, cotyledonary embryos and mature fruit zygotic
      embryos. Total soluble sugar levels increased sixfold at the initial stages of
      somatic embryogenesis induction. During this period, total soluble sugar in the
      cultures contained approximately 99.3% glucose and fructose. At 67.4 MUg/mg MS,
      no significant changes were observed in total sugar content during the embryo's
      somatic maturation and regeneration. During this stage, total soluble sugar was
      composed of 60% sucrose. After primary callus formation, starch contents
      increased gradually until the culture's conclusion. Total free amino acids,
      particularly arginine, lysine, methionine, asparagine, glutamine and histidine,
      revealed a higher synthesis until the formation of the primary callus, after
      which they remain statistically constant up to the end of the process. During the
      induction of calluses, a gradual increase of total proteins occurred, which, in
      the differentiating and maturing of somatic embryos, did not differ statistically
      till the formation of a cotyledonary embryo, when rates decreased 21.8%.

PMID- 29651375
TI  - Codon optimization significantly enhanced the expression of human 37-kDa iLRP in
      Escherichia coli.
AB  - 37-kDa immature laminin receptor protein (iLRP), the precursor of 67-kDa laminin
      receptor protein (LRP), is overexpressed on the surface of most cancer cells and
      recognized as a universal tumor antigen. The role makes it a potential target for
      cancer immunotherapy, which has been well-studied. Our study aimed to produce
      high quality of human iLRP in bacteria so that the needs in research of its
      clinical application could be met. The powerful system for heterologous protein
      expression, pET system was used. Two types of DNA sequences encoding the same
      amino acid sequences were separately cloned into the vector pET30a(+). One of the
      resulting vectors includes the wild-type iLRP, and other one includes the codon
      optimized iLRP. The expression by both genes was then compared in Escherichia
      coli BL21(DE3). Our results revealed that the performance of codon optimization
      was crucial for the expression of human iLRP in Escherichia coli. The yield was
      significantly enhanced up to 300 mg/L of bacterial culture by this approach.

PMID- 29651376
TI  - Synthesis, characterization and application of lipase-conjugated citric acid
      coated magnetic nanoparticles for ester synthesis using waste frying oil.
AB  - In the present work, magnetic nanoparticles (MNPs) were prepared by chemical
      precipitation of trivalent and divalent iron ions which were functionalized using
      citric acid. The bacterial isolate Staphylococcus epidermidis KX781317 was
      isolated from oil-contaminated site. The isolate produced lipase, which was
      purified and immobilized on magnetic nanoparticles (MNPs) for ester synthesis
      from waste frying oil (WFO). The characterization of MNPs employed conventional
      TEM, XRD and FTIR techniques. TEM analysis of MNPs showed the particle size in
      the range of 20-50 nm. FTIR spectra revealed the binding of citric acid to Fe3O4
      and lipase on citric acid-coated MNPs. The citric acid-coated MNPs and lipase
      conjugated citric acid-coated MNPs had similar XRD patterns which indicate MNPs
      could preserve their magnetic properties. The maximum immobilization efficiency
      98.21% of lipase-containing citric acid-coated MNPs was observed at ratio 10:1 of
      Cit-MNPs:lipase. The pH and temperature optima for lipase conjugated with Cit
      MNPs were 7 and 35  degrees C, respectively. Isobutanol was found to be an
      effective solvent for ester synthesis and 1:2 ratio of oil:alcohol observed
      significant for ester formation. The ester formation was determined using TLC and
      the % yield of ester conversion was calculated. The rate of ester formation is
      directly proportional to the enzyme load. Formed esters were identified as
      isobutyl laurate ester and isobutyl myristate ester through GC-MS analysis.

PMID- 29651377
TI  - Renoprotective effect of cinnamaldehyde in food color induced toxicity.
AB  - Present study reports the effects of metanil yellow, a non-permitted food
      colouring dye, on the biomarkers of oxidative stress and kidney function in blood
      and renal tissue of albino Wistar rats and its mitigation by cinnamaldehyde, a
      major phytoconstituents of cinnamon. Oral administration of metanil yellow in
      rats caused about 70% reduction in ferric reducing ability (FRAP 5.1 MUM/L) and
      50% decline in reduced glutathione (GSH 59.27 nM/mg protein) content in plasma
      with simultaneous increase in serum creatinine level. In kidney tissues,
      activities of superoxide dismutase (SOD), catalase and GSH dropped while
      malondialdehyde (MDA) content increased. Co-administration of cinnamaldehyde with
      metanil yellow showed considerable restorative effect on the biomarkers of plasma
      antioxidant status and kidney function i.e., FRAP (11.5 MUM/L), GSH (83-88.5
      nM/mg protein), urea, creatinine, SOD, catalase and MDA. Administration of
      cinnamaldehyde restored the kidney enzyme activities up to 75% of the base level.
      The study revealed that reno-protective action of cinnamaldehyde was mediated by
      lowering oxidative stress level.

PMID- 29651378
TI  - High-titer and productivity of l-(+)-lactic acid using exponential fed-batch
      fermentation with Bacillus coagulans arr4, a new thermotolerant bacterial strain.
AB  - Bacillus coagulans arr4 is a thermotolerant microorganism with great
      biotechnological potential for l-(+)-lactic acid production from granulated sugar
      and yeast extract. The highest l-(+)-lactic acid production was obtained with
      Ca(OH)2. The maximum production of l-(+)-lactic acid (206.81 g/L) was observed in
      exponential feeding using granulated sugar solution (900 g/L) and yeast extract
      (1%) at 50  degrees C, pH 6.5, and initial granulated sugar concentration of 100
      g/L at 39 h. 5.3 g/L h productivity and 97% yield were observed, and no sugar
      remained. Comparing the simple batch with exponential fed-batch fermentation, the
      l(+) lactic acid production was improved in 133.22% and dry cell weight was
      improved in 83.29%, using granulated sugar and yeast extract. This study presents
      the highest productivity of lactic acid ever observed in the literature, on the
      fermentation of thermotolerant Bacillus sp. as well as an innovative and high
      efficiency purification technology, using low-cost substances as Celite and
      charcoal. The recovery of lactic acid was 86%, with 100% protein removal, and the
      fermentation medium (brown color) became a colorless solution.

PMID- 29651379
TI  - Molecular cloning and characterization of Pif gene from pearl mussel, Hyriopsis
      cumingii, and the gene expression analysis during pearl formation.
AB  - In the present study, the Pif gene of the freshwater pearl aquaculture mussel,
      Hyriopsis cumingii (HcPif) was successfully cloned and functionally
      characterized. The full sequence of HcPif gene consists of 3415 base pairs, which
      putatively encode two proteins, HcPif90 and HcPif80. A sequence analysis revealed
      that HcPif contained a von Willebrand factor type A domain and a chitin-binding
      domain, and shared many functional residues with other Pif homologues. A highly
      conserved sequence, FKGLDEIELML, at the C-terminus of Pif80s was identified as
      the key functional site. The corresponding peptide fragment markedly modified the
      morphology of calcite crystallites in CaCO3 crystallization assay and might play
      an essential role in the interactive binding between HcPif80 and CaCO3. Moreover,
      real-time PCR results showed that HcPif gene was dominantly expressed in the
      pearl secreting tissues and its expression changed in response to the different
      development status of the pearl sac during pearl aquaculture. The gene expression
      of HcPif was maximum 7 days after mantle grafting and declined to about the
      control level on day 30. Our in vitro and in vivo experimental data indicated
      that HcPif gene possessed the inherent characteristics of a nacre formation gene
      and its expression might faithfully reflect the pearl secretion status of the
      pearl mussels examined. Our findings may extend the understanding of the
      biomineralization mechanism of nacre formation and provide a potential biomarker
      for pearl farming.

PMID- 29651380
TI  - A combined pathway of organogenesis and somatic embryogenesis for an efficient
      large-scale propagation in date palm (Phoenix dactylifera L.) cv. Mejhoul.
AB  - An efficient regeneration system via a combined pathway of organogenesis and
      somatic embryogenesis was developed for date palm (Phoenix dactylifera L.) cv.
      Mejhoul. Adventitious buds were obtained from shoot-tip explants with a frequency
      of 53.3% after 9 months of culture: 6 months on half-strength Murashige and Skoog
      (MS/2) medium containing 14.2 uM indole-3-acetic acid (IAA), 13.4 uM 1
      naphthaleneacetic acid (NAA) and 0.5 uM 6-(dimethylallylamino) purine (2iP), and
      3 months on MS/2 medium supplemented with 1.1 uM IAA, 1.1 uM NAA, 0.5 uM 2iP, 2.2
      uM 6-benzyladenine (BA) and 0.4 uM kinetin. Adventitious bud segments were used
      as explants to induce somatic embryogenesis, and the effects of different
      concentrations (22.5, 45, 90, 225 or 450 uM) of 3,6-dichloro-o-anisic acid
      (dicamba) and 4-amino-3,5,6-trichloropicolinic acid (picloram) were evaluated.
      The optimal medium for somatic embryogenesis induction was MS medium supplemented
      with 45 uM picloram and 5 uM 2iP, in which the somatic embryogenesis rate was
      70%. For somatic embryo maturation, the effects of sorbitol, mannitol,
      polyethylene glycol (PEG) and abscisic acid (ABA) were tested. The highest
      maturation rate (88.6 mature somatic embryos per 100 mg fresh weight callus) was
      observed on liquid MS medium supplemented with 20 g L-1 PEG. Subsequent somatic
      embryo germination was achieved with up to 52.0% in MS medium containing 2.5 uM
      NAA and 2.5 uM BA. The regenerated plantlets were transferred to the glasshouse
      where 76.0% of them survived.

PMID- 29651382
TI  - Impact of geography on adaptation of Phyllanthus amarus seeds.
AB  - The present study was aimed to evaluate adaptive mechanism in terms of seed
      characters of Phyllanthus amarus collected from ten different locations of Tamil
      Nadu, India. The adaptive variations among the collected populations were
      assessed based on the sink and float percentages of the seeds in water, the
      percentage of seed germination, total protein, carbohydrates and their seedling's
      growth ability such as shoot and root lengths. From this, we observed that the
      population had a significantly higher germination percentage of sinking seeds
      that were attributed to its relatively higher carbohydrate and protein contents
      than the floating seeds. A comparison of the seed population by cluster analysis
      and principal coordinate analysis showed that the Chennai population constituted
      a single clade that was very distinct from the other nine populations, which were
      further grouped into two sub-clusters. They exhibited a trend consistent with
      their geographical proximity. Standardised Mantel's t tests had revealed that the
      adaptive diversity of the P. amarus population was significantly affected by the
      geographic distance (r = 0.78, t = 2.68, P > 0.001), altitude (r = 0.35, t =
      21.53, P > 0.05), minimum temperature (r = 0.43, t = 1.49, P > 0.01) and maximum
      temperature (r = 0.49, t = 1.67, P > 0.001). Seed's characteristics and
      geographical conditions were correlated along with 19 bioclimatic variables. In
      dry season, the seedling's rooting ability showed positive correlation, while its
      protein content exhibited a negative correlation. It is clearly evident from this
      study that the geographical variables significantly influence the adaptive
      ability of the P. amarus.

PMID- 29651381
TI  - Recent advances in conventional and contemporary methods for remediation of heavy
      metal-contaminated soils.
AB  - Remediation of heavy metal-contaminated soils has been drawing our attention
      toward it for quite some time now and a need for developing new methods toward
      reclamation has come up as the need of the hour. Conventional methods of heavy
      metal-contaminated soil remediation have been in use for decades and have shown
      great results, but they have their own setbacks. The chemical and physical
      techniques when used singularly generally generate by-products (toxic sludge or
      pollutants) and are not cost-effective, while the biological process is very slow
      and time-consuming. Hence to overcome them, an amalgamation of two or more
      techniques is being used. In view of the facts, new methods of biosorption,
      nanoremediation as well as microbial fuel cell techniques have been developed,
      which utilize the metabolic activities of microorganisms for bioremediation
      purpose. These are cost-effective and efficient methods of remediation, which are
      now becoming an integral part of all environmental and bioresource technology. In
      this contribution, we have highlighted various augmentations in physical,
      chemical, and biological methods for the remediation of heavy metal-contaminated
      soils, weighing up their pros and cons. Further, we have discussed the
      amalgamation of the above techniques such as physiochemical and physiobiological
      methods with recent literature for the removal of heavy metals from the
      contaminated soils. These combinations have showed synergetic effects with a many
      fold increase in removal efficiency of heavy metals along with economic
      feasibility.

PMID- 29651383
TI  - Influence of encoding instructions and response bias on cross-cultural
      differences in specific recognition.
AB  - Prior cross-cultural research has reported cultural variations in memory. One
      study revealed that Americans remembered images with more perceptual detail than
      East Asians (Millar et al. in Cult Brain 1(2-4):138-157, 2013). However, in a
      later study, this expected pattern was not replicated, possibly due to
      differences in encoding instructions (Paige et al. in Cortex 91:250-261, 2017).
      The present study sought to examine when cultural variation in memory-related
      decisions occur and the role of instructions. American and East Asian
      participants viewed images of objects while making a Purchase decision or an
      Approach decision and later completed a surprise recognition test. Results
      revealed Americans had higher hit rates for specific memory, regardless of
      instruction type, and a less stringent response criterion relative to East
      Asians. Additionally, a pattern emerged where the Approach decision enhanced hit
      rates for specific memory relative to the Purchase decision only when
      administered first; this pattern did not differ across cultures. Results suggest
      encoding instructions do not magnify cross-cultural differences in memory.
      Ultimately, cross-cultural differences in response bias, rather than memory
      sensitivity per se, may account for findings of cultural differences in memory
      specificity.

PMID- 29651385
TI  - Clinicopathological predictors of long-term benefit in breast cancer treated with
      neoadjuvant chemotherapy.
AB  - AIM: To investigate the survival impact of clinicopathological factors, including
      pathological complete response (pCR) and tumor-infiltrating lymphocytes (sTIL)
      levels according to subtypes, in breast cancer (BC) patients who received neo
      adjuvant chemotherapy (NAC). METHODS: We evaluated 435 BC patients who presented
      and received NAC at the Instituto Nacional de Enfermedades Neoplasicas from 2003
      to 2014. sTIL was analyzed as the proportion of tumor stroma occupied by
      lymphocytes, and was prospectively evaluated on hematoxylin and eosin-stained
      sections of the preNAC core biopsy. pCR was considered in the absence of
      infiltrating cancer cells in primary tumor and axillary lymph nodes. Analysis of
      statistical association between clinical pathological features, sTIL, pCR and
      survival were carried out using SPSSvs19. RESULTS: Median age was 49 years (range
      24-84 years) and the most frequent clinical stage was IIIB (58.3%). Luminal A,
      Luminal B, HER2-enriched and (triple-negative) TN phenotype was found in 24.6%,
      37.9%, 17.7% and 19.8%, respectively. pCR was observed in 11% and median
      percentage of sTIL was 40% (2%-95%) in the whole population. pCR was associated
      to Ct1-2 (P = 0.045) and to high sTIL (P = 0.029) in the whole population. There
      was a slight trend towards significance for sTIL (P = 0.054) in Luminal A. sTIL
      was associated with grade III (P < 0.001), no-Luminal A subtype (P < 0.001), RE
      negative (P < 0.001), PgR-negative (P < 0.001), HER2-positive (P = 0.002) and pCR
      (P = 0.029) in the whole population. Longer disease-free survival was associated
      with grade I-II (P = 0.006), cN0 (P < 0.001), clinical stage II (P = 0.004), ER
      positive (P < 0.001), PgR-positive (P < 0.001), luminal A (P < 0.001) and pCR (P
      = 0.002). Longer disease-free survival was associated with grade I-II in Luminal
      A (P < 0.001), N0-1 in Luminal A (P = 0.045) and TNBC (P = 0.01), clinical stage
      II in Luminal A (P = 0.003) and TNBC (P = 0.038), and pCR in TNBC (P < 0.001).
      Longer overall survival was associated with grade I-II (P < 0.001), ER-positive
      (P < 0.001), PgR-positive (P < 0.001), Luminal A (P < 0.001), cN0 (P = 0.002) and
      pCR (P = 0.002) in the whole population. Overall survival was associated with
      clinical stage II (P = 0.017) in Luminal A, older age (P = 0.042) in Luminal B,
      and pCR in TNBC (P = 0.005). CONCLUSION: Predictive and prognostic values of
      clinicopathological features, like pCR and sTIL, differ depending on the
      evaluated molecular subtype.

PMID- 29651386
TI  - Tissue Engineering in Maxillary Bone Defects.
AB  - BACKGROUND: Restoration of craniofacial bone defects has been a concern for oral
      and maxillofacial surgeons. In this study, the healing effect of fibrin glue
      scaffold was compared with autologous bone graft in mandibular defects of rabbit.
      METHODS: Bilateral unicortical osteotomy was performed in the diastema region of
      10 male Dutch rabbits. The subjects were randomly divided into 2 equal groups.
      The mandibular defect on the right side was treated with fibrin glue scaffold and
      the defect on the left side with autologous bone graft provided from iliac crest.
      After 4 and 8 weeks, five rabbits from each group were sacrificed and the defects
      were evaluated morphologically, by coronal computed tomography scanning (CT-scan)
      and by histological examinations. RESULTS: The healing effect of fibrin glue
      scaffold and autologous bone graft was similar with appropriate osteogenesis in
      comparison to the control group. CONCLUSION: Using fibrin glue can be a non
      invasive treatment of choice in mandibular defects and maxillofacial surgeries
      when compared with autologous bone graft.

PMID- 29651384
TI  - Cell-free DNA integrity for the monitoring of breast cancer: Future perspectives?
AB  - Breast cancer (BC) is the most common cancer and the second cause of death in
      women worldwide. Therapeutic options are increasing, but the response to
      treatments is not always efficient and the risk of recurrence covers decades. In
      this perspective, the need to have a proper follow-up for the therapeutic
      responses and for anticipating recurrence it is urgent in the clinical setting.
      Liquid biopsy provides the basic principle for a non-invasive method for the
      routinely monitoring of BC. However, due to the heterogeneity of tumors during
      onset and progression, the search for tumor DNA mutations of targeted genes in
      plasma/serum is a limiting factor. A possible approach overtaking this problem
      comes from the measurement of cell-free DNA integrity, which is an independent
      factor from the mutational status and theoretically is representative of all
      tumors. This review summarizes the state-of-the-art of cell-free DNA integrity
      researches in BC, the controversies and the future perspective.

PMID- 29651387
TI  - Synchronous Soleus and Reverse Sural Flap for Large Soft Tissue Defect
      Reconstruction of Leg.
AB  - BACKGROUND: Extended Soft tissue defect of leg including middle and distal parts
      always has been a challenge for many plastic surgeons and also a frustrated
      problem for patients and families. To introduce the use of the soleus muscle and
      reverse sural flaps as synchronous surgical treatment alternative of the leg bone
      exposure with large soft tissue defect, this study was conducted. METHODS: The
      medical records of patients undergoing transposition of the soleus muscle for
      treating exposed bone in the leg and simultaneous sural flap were retrospectively
      analyzed from January 2009 to July 2014, while gathering information on the used
      muscle was to cover the lesion. RESULTS: Twelve patients with varying ages
      between 22 and 58 years (10 males and 2 females) were enrolled. The main initial
      injury was trauma (84.8%), consisting of tibia and/or fibula fractures. Only 1
      patient developed insignificant distal flap necrosis who was treated subsequently
      with surgical debridement and flap re-advancement. CONCLUSION: The treatment of
      bone exposure with local muscle flaps (soleus and sural) enables obtaining
      satisfactory results in covering of exposed structures, favoring local
      vascularization and improving the initial injury. It offers the advantage of
      providing a treatment in only one surgical procedure, an earlier recovery and
      reduced hospital stay. Sometimes, this method may be applied instead of free
      tissue transfer.

PMID- 29651388
TI  - The Effect of Oral Propranolol versus Oral Corticosteroids in Management of
      Pediatric Hemangiomas.
AB  - BACKGROUND: Hemangiomas are the most common benign tumors of infancy. This study
      evaluated the efficacy of oral propranolol comparing to oral steroids in
      management of pediatric hemangiomas. METHODS: In North India from January 2012 to
      January 2015, sixty children <6 years old with superficial hemangiomas were
      divided into 2 groups; oral propranolol vs. oral prednisolone. All participants
      were assessed for electrocardiogram, heart rate, blood pressure and sugar and
      initial therapy was started using 1 mg/kg and in absence of adverse effects, 2
      mg/kg was administered after 2 weeks. The hemangioma Activity Score (HAS) was
      used for scoring and patients were followed up for 6 months. RESULTS: The
      propranolol group mostly showed early response to the drug and needed the drug
      for less time compared to corticosteroid group. In propranolol group, 16.5%, 23%
      and 59% needed the drug to be continued for 8-12, 4-8 and 4 months. In
      corticosteroid group, the therapy was continued for 8-12, and 4-8 months in 76.8%
      and 16.5% and in 6.6% was stopped within 4 months. In propranolol group, the
      response was 70% compared to 40% in other group. The mean HAS decreased
      significantly in propranolol group when compared to steroid group. Three patients
      on prednisolone developed Cushingoid features, while 1 patient in propranolol
      group had mild flue like symptoms. CONCLUSION: Two mg/kg of oral propranolol
      significantly decreased HAS, when compared to oral prednisolone, with good parent
      satisfaction, minimal adverse effects and no recurrence/relapse of hemangiomas
      after a follow up period of 6 months.

PMID- 29651390
TI  - Comparison of Albizia Julibressin and Silver Sulfadiazine in Healing of Second
      and Third Degree Burns.
AB  - BACKGROUND: Large numbers of population suffer from burn annually. The promising
      treatment of burn has not been identified yet. Albizia julibressin (A.
      julibressin) in Fabaceae family is popular for its antiseptic activity. This
      prospective study was designed to compare the wound healing effects of A.
      julibressin gel (AG) with silver sulfadiazine (SSD). METHODS: This single blind
      clinical trial was performed on 40 patients with second and third degree burns.
      20 patients treated with SSD and 20 other patients received A. julibressin. The
      percentage of the wound healing was evaluated with pain, irritation, edema,
      itching, erythema, purulent discharges and skin discoloration symptoms. Also, the
      patients' satisfaction and adverse drug reactions were determined. RESULTS: The
      severity of pain (p=0.03), inflammation (p=0.02) and purulent secretions (p=0.03)
      were significantly relieved in A. julibressin group. The healing time
      significantly reduced in second degree burns (p=0.03) and third degree burns
      (p=0.04) with treating by A. julibressin. No significant adverse drug reactions
      were detected with A. julibressin. CONCLUSION: It seems that A. julibressin
      improves the different therapeutic aspects of burn injuries and could be
      considered as a new herbal remedy in wound healings.

PMID- 29651389
TI  - The Healing Effect of N-Hexan- Dichloromethane Extract Root Onosma Bulbotrichum
      in Second Degree Burns.
AB  - BACKGROUND: Wound healing is the process of repair following an injury to the
      skin and other soft tissues. In this study, the effect of n-hexane d
      chloromethane extract (1: 1) of root Onosma bulbotrichum DC on the second degree
      burn in rabbit model was investigated. METHODS: Thirty-six adult rabbits of both
      sexes were randomly divided into six groups, control (without treatment),
      negative control (treatment with cold cream), positive control (treatment with
      silver sulfadiazine), and treatment groups with 5%, 1% and 2% O. bulbotrichum
      cream and assessed histologically. RESULTS: The best result was shown in 5% O.
      bulbotrichum group similar to silver sulfadiazine group. The maximum amount of
      collagen and the tensile strength of tissue were observed in 5% O. bulbotrichum
      and silver sulfadiazine groups. Histopathological examination showed that burn
      healing in treatment group with 5% O. bulbotrichum was faster than other groups.
      CONCLUSION: The 5% O. bulbotrichum cream was shown to have healing, and anti
      inflammatory effects when used in treatment of second degree burns.

PMID- 29651391
TI  - The Wound Healing Effects of Herbal Cream Containing Oliveria Decumbens and
      Pelargonium Graveolens Essential Oils in Diabetic Foot Ulcer Model.
AB  - BACKGROUND: The number of diabetic patients in adult population is increasing.
      All this population are at risk of developing diabetic foot ulcers (DFUs) that
      are associated with unwanted ailments and high mortality. In spite of current
      therapies for DFUs, further therapies are needed to help the patients. METHODS:
      The efficacy of herbal cream containing Pelargonium graveolens and Oliveria
      decombens essential oils was evaluated topically for treatment of DFUs in rat
      animal model in comparison with two other herbal formulas containing each
      essential oil alone, placebo (the basic formula without active ingredients) and
      normal saline as control groups. After anesthesia of diabetic rats (n=75) induced
      by streptozotocin (STZ), diabetic wounds were visible on the hind dorsal surface
      of the foot. The treatments were initiated on Day 1 and repeated 3 times a day
      for thirteen consecutive days. On day 1, 3, 5, 8 and 13, the wound sizes were
      determined and assessed histologically. RESULTS: Three herbal formulations
      reduced the size of wounds in rats with DFUs, while the cream containing combined
      herbals of O. decumbens and P. graveolens essential oils had the highest tissue
      repair in DFU rat models. CONCLUSION: Due to better wound healing effects of
      combined herbal cream containing O. decumbens and P. graveolens essential oils,
      it can be recommended in treatment of DFUs.

PMID- 29651392
TI  - The Effect of Rhythmic Breathing on Pain of Dressing Change in Patients with
      Burns Referred to Ayatollah Mousavi Hospital.
AB  - BACKGROUND: Burn is the worst tragedy among modern societies that individuals may
      experience. One of the most important problems of burns is pain; particularly at
      the time of treatment including burn dressings, debridement, surgical incisions
      and physiotherapy. The aim of this study was to determine the effect of rhythmic
      breathing on pain of dressing change in patients with burns. METHODS: This semi
      experimental clinical trial study with a control group was conducted on 60
      eligible burn patients who were selected using convenient sampling method and
      allocated randomly in two groups of test and control (each n=30). Data collection
      tools included demographic data and pain observation questionnaires. The rhythmic
      breathing was individually and orally trained to the patients of test group in a
      room separated by dividers for a 20-minute session. The pain intensity in test
      and control groups before and after dressing was investigated for three
      consecutive days. RESULTS: Friedman test results showed that pain intensity in
      both control and test groups had statistically significant differences. The pain
      intensity after rhythmic breathing reduced more in the test group, and this
      reduction was more significant during 3 days. CONCLUSION: Rhythmic breathing is
      an effective method on pain reduction of dressing change in patients with burn
      injuries.

PMID- 29651393
TI  - Wound Healing Potential of Intermittent Negative Pressure under Limited Access
      Dressing in Burn Patients: Biochemical and Histopathological Study.
AB  - BACKGROUND: Malondialdehyde (MDA) is an oxidant that causes damage to membranes,
      DNA, proteins, and lipids at the cellular level. Antioxidants minimize the
      effects of oxidants and thus help in formation of healthy granulation tissues
      with higher level of hydroxyproline and total protein. This study compared the
      effect of limited access dressing (LAD) with conventional closed dressing
      biochemically and histopathologically. METHODS: Seventy-two 12-65 years old burn
      patients with mean wound size of 14 cm2 were divided to two groups of LAD (n=37),
      and conventional dressing groups (n=35). Various biochemical parameters were
      measured in granulation tissue. Histopathological analysis of the granulation
      tissue was studied too. RESULTS: LAD group showed significant increase in
      hydroxyproline, total protein, GSH, and GPx and decrease in MDA levels compared
      to conventional dressing group. A significant negative correlation between GSH
      and MDA was noted in LAD group, but in conventional dressing group there was no
      significant correlation. A significant negative correlation between GPx and MDA
      was noticed in LAD group, but in conventional dressing group was not significant.
      There was a histologically fewer inflammatory cells, increased and well organized
      extracellular matrix deposit, more angiogenesis in LAD group after 10 days while
      the difference was significant between the groups. CONCLUSION: Our study showed a
      significant reduction in oxidative stress biomarker of MDA, increase in
      hydroxyproline, total protein, antioxidants and amount of ECM deposition, number
      of blood vessels and a decrease in the amount of inflammatory cells and necrotic
      tissues in LAD group indicating the better healing effect of burn wounds.

PMID- 29651394
TI  - The Healing Effect of Sesame Oil, Camphor and Honey on Second Degree Burn Wounds
      in Rat.
AB  - BACKGROUND: Many studies were carried out to improve sophisticated dressings to
      accelerate healing processes and reduce the microbial burden in burn wounds. This
      study evaluated the healing effect of herbal ointment containing extract of
      sesame oil, camphor and honey on second degree burn wounds in rats in comparison
      with daily dressing oil vaseline. METHODS: Forty rats were randomly assigned to
      two equal groups. A deep second degree burn was formed on the back of each rat
      with using a standard burning technique. The burns were dressed daily with herbal
      ointment containing extract of sesame oil, camphor and honey in group 1, dressing
      oil vaseline in group 2. The response to treatment was evaluated by digital
      photography during the treatment on 0, 7, 14, 21, 28 days. Histological scoring
      was undertaken for scar tissue samples on 0, 7, 14, 21, 28 days. RESULTS:
      Considerable epithelization in the herbal ointment group vs. the control group
      over the study period was noted. Neovascularization was significantly higher in
      herbal ointment treated rats as well. In terms of difference of wound surface
      area, maximal healing was noticed in herbal ointment extract of sesame oil,
      camphor and honey group and the minimal repair in the control group. CONCLUSION:
      The greatest rate of healing was in the herbal ointment group containing sesame
      oil, camphor and honey, so the herbal ointment as a suitable substitute for
      dressing and healing of burn wound injuries is recommended.

PMID- 29651395
TI  - Fat Grafting Technique, A Paradigm Shift in the Treatment of Tuberous Breast.
AB  - BACKGROUND: The tuberous breast syndrome is a condition that affects young women
      and can bring on serious disorders of self-esteem. There are numerous surgical
      techniques to correct this condition, but most of them include the use of breast
      implants to replace lack of volume. Nowadays, patients are increasingly becoming
      more demanding to get a definitive solution with minimal aesthetic sequelae.
      METHODS: We present a series of 11 patients with tuberous breast deformities
      treated with lipofilling technique. Fat harvest was performed by conventional
      lipoaspiration with 3 mm cannulas, centrifuged at 2000 rpm for 2 minutes and
      injected in the breast were was needed with 1.9 mm blunt cannulas. RESULTS: The
      patient's average age was 24 year old with a BMI of 23.4 kg/m2. Volumes between
      80 and 250 ml per breast were injected in every session, requiring a total volume
      of 413 ml per breast. Most patients required up to two procedures to achieve the
      complete breast correction. The mean follow-up was 29.7 months. All patients had
      good aesthetics results with minimal complications. CONCLUSION: Natural breast
      mound with excellent cosmetic result can be achieved with fat grafting. Fat
      grafting main advantage is to respond to physiological changes in weight over
      time. In addition, lipofilling do not carry the inherent complications of
      implants. We strongly believe it is a safe and easy technique to reproduce in
      properly selected patients and with minimal morbidity it can cause the best
      natural result.

PMID- 29651396
TI  - Correcting Flank Skin Laxity and Dog Ear Plus Aggressive Liposuction: A Technique
      for Classic Abdominoplasty in Middle-Eastern Obese Women.
AB  - BACKGROUND: Nowadays obesity is a common problem as it leads to abdominal
      deformation and people's dissatisfaction of their own body. This study has
      explored using a new surgical technique based on a different incision to reform
      the flank skin laxity and dog ear plus aggressive liposuction on women with
      abdominal deformities. METHODS: From May 2014 to February 2016, 25 women were
      chosen for this study. All women had a body mass index more than 28 kg/m2, flank
      folding, bulging and excess fat, abdominal and flank skin sagging and laxity. An
      important point of the new technique was that the paramedian perforator was
      preserved. RESULTS: All women were between 33 and 62 years old (mean age of 47+/
      7.2 years old). The average amount of liposuction aspirate was 2,350 mL (1700
      3200 mL), and the size of average excised skin ellipse was 23.62*16.08 cm (from
      19*15 to 27*18 cm). Dog ear, skin laxity, bulging and fat deposit correction were
      assessed and scored in two and four months after the surgery. CONCLUSION:
      Aggressive abdominal and flank liposuction can be safely done when paramedian
      perforator is preserved. This has a good cosmetic result in the abdomen and flank
      and prevents bulging in the incision end and flank. Using this abdominoplasty
      technique is recommended on patients with high body mass indexes.

PMID- 29651397
TI  - Readability of Online Materials for Rhinoplasty.
AB  - BACKGROUND: Rhinoplasty is a popular aesthetic and reconstructive surgical
      procedure. However, little is known about the content and readability of online
      materials for patient education. The recommended grade level for educational
      materials is 7th to 8th grade according to the National Institutes of Health
      (NIH). This study aims to assess the readability of online patient resources for
      rhinoplasty. METHODS: The largest public search engine, Google, was queried using
      the term "rhinoplasty" on February 26, 2016. Location filters were disabled and
      sponsored results excluded to avoid any inadvertent search bias. The 10 most
      popular websites were identified and all relevant, patient-directed information
      within one click from the original site was downloaded and saved as plain text.
      Readability was analyzed using five established analyses (Readability-score.com,
      Added Bytes, Ltd., Sussex, UK). RESULTS: Analysis of ten websites demonstrates an
      average grade level of at least 12th grade. No material was at the recommended
      7th to 8th grade reading level (Flesch-Kincaid, 11.1; Gunning-Fog, 14.1; Coleman
      Liau, 14.5; SMOG 10.4; Automated Readability, 10.7; Average Grade Level, 12.2).
      Overall Flesch-Kincaid Reading Ease Index was 43.5, which is rated as
      "difficult." CONCLUSION: Online materials available for rhinoplasty exceed NIH
      recommended reading levels, which may prevent appropriate decision-making in
      patients considering these types of surgery. Outcomes of this study identify that
      Plastic Surgeons should be cognizant of available online patient materials and
      make efforts to develop and provide more appropriate materials. Readability
      results can also contribute to marketing strategy and attracting a more
      widespread interest in the procedure.

PMID- 29651399
TI  - Charlin'S Syndrome Following a Routine Septorhinoplasty.
AB  - There are some rare but probable devastating complications following any
      rhinoplasty. Charlin's syndrome is a typical one. It is completely related to the
      external nasal nerve. In this report, we are presenting a 21-year-old female with
      signs and symptoms of Charlin's syndrome, persisting for 4 years after a routine
      septorhinoplasty operation. Surgery was uneventful and the patient underwent bony
      septal resection and caudal septal relocation. Osteotomy was internal low to low
      and external transverse bilaterally. Overall, a routine septorhinoplasty was
      executed. Everything went well postoperatively, until 4 months after surgery,
      when some irritating symptoms developed and gradually intensified.

PMID- 29651398
TI  - Teenage Rhinoplasty.
AB  - BACKGROUND: Rhinoplasty is among the most popular aesthetic surgical procedures
      selected by teenagers. When it comes to teenagers' rhinoplasty, almost all
      surgeons believe that modified techniques should be considered because the nose
      is still growing. In this article, we prospectively followed teenagers who had
      undergone septorhinoplasty to assess the safety of procedure and its possible
      complications. METHODS: All the patients who were under 18 years old but for
      those who had a bleeding disorder, allergic rhinitis, and cleft lip nose were
      included in the study. All the patients were operated by the Senior author
      through closed rhinoplasty. Age, gender, indication for surgery, postoperative
      complications, need for revision surgery, postoperative satisfaction, and
      disturbance in facial growth until puberty were gathered for each of patients.
      RESULTS: Of all 40 patients, 38 (95%) patients were female and 2 (5%) patients
      were male. Mean age and follow up of patients was 16.1+/-0.8 years and 29.5+/
      12.1 months, respectively. Fourteen (35%) patients had some degrees of nasal
      obstruction. Thirty-five (87.5%) patients expressed complete satisfaction with
      their rhinoplasty outcome. None of patients underwent revision rhinoplasty.
      CONCLUSION: The study indicates that patients' craniofacial growth was not
      affected by the procedure, and it seems that septorhinoplasty is safe in
      teenagers.

PMID- 29651400
TI  - Management of a Case of Mucor Colonization in Breast Tissue Expander Seroma
      Pocket.
AB  - Mucormycosis has a mortality rate reaching 90%, and is imperative that therapy be
      initiated rapidly once a diagnosis is made. Successful treatment consists of
      management of underlying risk factors, surgical debridement, and antifungal
      therapies. The dilemma whether or not to pursue extensive debridement presents
      when the wound is cultured positive but the patient is not systemically ill. We
      present the first reported case of successful medical treatment of a seroma
      pocket colonized with mucor in a patient undergoing bilateral reconstruction with
      tissue expander and acellular dermal matrix.

PMID- 29651401
TI  - Rehabilitation of an Auricular Defect Using Surgical Stent.
AB  - Reconstruction of a facial defect is a complex modality either surgically or
      prosthetically, depending on the site, size, etiology, severity, age, and the
      patient's expectation. The loss of an auricle, in the presence of an auditory
      canal, affects hearing, because the auricle gathers sound and directs it into the
      canal. The auricle acts as a resonator to slightly amplify lower frequency sounds
      and helps to localize sounds, especially in conjunction with the other ear.
      Osseointegrated implants have an important role in the prosthetic reconstruction
      of patients with craniofacial defects. The main indications of this treatment
      plan are lack of local tissue for autogenous reconstruction, previous
      reconstruction failure and selection of this technique by the patient. This paper
      presents a clinical case and advantages of the osseointegrated implant technique
      for retention of auricular prostheses.

PMID- 29651402
TI  - Reconstruction of a Giant Wound Induced by Advanced Penile Carcinoma with
      Bilateral Anteromedial Thigh Flap and Left Deep Circumflex Iliac Artery Flaps.
AB  - A 39-year-old male patient presented with an extensive putrescent ulceration of
      abdominoperineal region infiltrated by advanced penile squamous cell carcinoma.
      To our knowledge, it is the largest defect after aggressive palliative resection
      of penile squamous cell carcinoma (pSCC) in the literature, which was 36*23 cm.
      The defect was divided into three sub-defects, and was repaired by bilateral
      anteromedial thigh (AMT) and left deep circumflex iliac artery (DCIA) flaps. The
      postoperative course was uneventful and no flap necrosis occurred. The symptom
      relief was excellent.

PMID- 29651403
TI  - Enhanced Wound Healing after Leiomyoma Enucleation.
AB  - Leiomyoma is a rare esophageal tumor that constitutes less than 1% of esophageal
      malignancies. It should be removed when diagnosed even if asymptomatic. This
      study presents two cases of esophageal leiomyoma in 38 and 62 years old men who
      presented with dysphagia and evaluated for diagnosis and location of related
      tumors. Patients were clinically examined and upper gastrointestinal endoscopy,
      chest computerized tomography scan, barium swallow and endoscopic ultrasonography
      were performed. The masses were diagnosed and both patients underwent 3-port
      right videothoracoscopic enucleation of esophageal leiomyoma with sleeve
      calibration tube (SCT) assistance. SCT was used to protrude out the mass from
      surrounding tissues. Also immunohistochemistry was done after mass enucleation.
      Two patients were operated routinely without any unpredictable events by help of
      SCT assistance. Mass size was 3.5*2.5*1 cm in one case and 1.5*1*0.5 cm in
      another patient. Positive smooth muscle antigen, desmin and ki67 and negative
      CD34, CD117 and S100 in both cases were obtained in immunohistochemistry.
      Patients were followed after surgery for 3 months and no complications were
      detected in none of them. Thoracoscopic enucleation of esophageal leiomyoma is a
      safe and feasible procedure which can decrease hospitalization and operation
      time. Based on our findings, the use of esophageal SCT help to detect smaller
      tumor without need of intra-operative endoscopy, facilitates separation of the
      tumor mass from both esophageal mucosal and muscular layers, and may prevent
      perforation. Finally, use of SCT makes the operation faster and safer.

PMID- 29651404
TI  - Unusual Evolution of Plexiform Neurofibroma in the Scalp: A Case Report.
AB  - The neurofibromatosis is a frequent and polymorphic genetic disorder. The
      severity is related to the complications. The degeneration of neurofibroma is a
      very rare complication of neurofibromatosis. In the literature, a few cases of
      solitary neurofibroma, which turned into a malignant tumor were reported. In our
      case, we described a very rare clinical case of neurofibrosarcoma in the scalp,
      and surgical treatment.

PMID- 29651405
TI  - Medial Laminectomy of the Large Concha Bullosa in Crooked Nose.

PMID- 29651406
TI  - A New Surgical Technique in Treatment of Nail Onycogryphosis.

PMID- 29651408
TI  - Patients with multimorbidity and their treatment burden in different daily life
      domains: a qualitative study in primary care in the Netherlands and Belgium.
AB  - Background: Physicians and other healthcare professionals involved in the care of
      patients with multimorbidity should consider the problems these patients
      experience in managing their own conditions. However, treatment burden from the
      patient's perspective has been poorly explored, even though this might hamper
      treatment adherence. Objective: The present study examined the experiences of
      patients with multimorbidity in primary care in the Netherlands and Belgium using
      semi-structured interviews, with special attention to the daily life domains of
      treatment burden. Design: Individual interviews gathering qualitative data to
      explore the treatment burden experienced by patients with multimorbidity in
      primary care. Twenty-two patients agreed to participate: seven men and fifteen
      women. The recorded interviews were transcribed verbatim and evaluated using
      thematic content analysis. Results: The patients reported numerous aspects of
      treatment burden they experienced in various domains of their daily lives. These
      topics were categorized into four daily life domains of burden: organization of
      care, medication, patient's role, and impact on daily life (including the
      involvement of caregivers). Conclusions: The findings indicate that primary care
      patients with multimorbidity report treatment burden in several domains of their
      daily lives, not restricted to medical issues, such as side effects of
      medication. Some issues, such as those related to organization of care, seem
      easily modifiable. Further research is required focusing on special factors of
      treatment burden as experienced by patients with multimorbidity, and the
      implications for treatment adherence, especially in European settings, as little
      information is currently available.

PMID- 29651407
TI  - Combination Therapy With Histone Deacetylase Inhibitors (HDACi) for the Treatment
      of Cancer: Achieving the Full Therapeutic Potential of HDACi.
AB  - Genetic and epigenetic changes in DNA are involved in cancer development and
      tumor progression. Histone deacetylases (HDACs) are key regulators of gene
      expression that act as transcriptional repressors by removing acetyl groups from
      histones. HDACs are dysregulated in many cancers, making them a therapeutic
      target for the treatment of cancer. Histone deacetylase inhibitors (HDACi), a
      novel class of small-molecular therapeutics, are now approved by the Food and
      Drug Administration as anticancer agents. While they have shown great promise,
      resistance to HDACi is often observed and furthermore, HDACi have shown limited
      success in treating solid tumors. The combination of HDACi with standard
      chemotherapeutic drugs has demonstrated promising anticancer effects in both
      preclinical and clinical studies. In this review, we summarize the research thus
      far on HDACi in combination therapy, with other anticancer agents and their
      translation into preclinical and clinical studies. We additionally highlight the
      side effects associated with HDACi in cancer therapy and discuss potential
      biomarkers to either select or predict a patient's response to these agents, in
      order to limit the off-target toxicity associated with HDACi.

PMID- 29651409
TI  - Incidence of comorbidities in women with breast cancer treated with tamoxifen or
      an aromatase inhibitor: an Australian population-based cohort study.
AB  - Background: The development of comorbidities has become increasingly relevant
      with longer-term cancer survival. Objective: To assess the pattern of
      comorbidities among Australian women with breast cancer treated with tamoxifen or
      an aromatase inhibitor. Design: Retrospective cohort study using Pharmaceutical
      Benefits Scheme (PBS) data (10% sample) from January 2003 to December 2014.
      Dispensing claims data were used to identify comorbidities and classified with
      the Rx-Risk-V model. The breast cancer cohort had tamoxifen or an aromatase
      inhibitor dispensed between 2004 and 2011 with no switching between types of
      endocrine therapy. Comparisons were made between the breast cancer cohort and
      specific control groups (age- and sex-matched at 1:10 ratio without any
      dispensing of anti-neoplastic agents during the study period) for the development
      of five individual comorbidities over time using Cox regression models. Results:
      Women treated with tamoxifen had a higher incidence of cardiovascular conditions,
      diabetes, and pain or pain-inflammation, but a lower incidence of hyperlipidaemia
      compared with non-cancer control groups, as indicated by PBS data. Women treated
      with aromatase inhibitors were more likely to develop cardiovascular conditions,
      osteoporosis, and pain or pain-inflammation compared with non-cancer control
      groups. The risks of hyperlipidaemia and osteoporosis were significantly lower
      among tamoxifen users compared with aromatase inhibitor users. Conclusions: Women
      with hormone-dependent breast cancer treated with an endocrine therapy had a
      higher risk of developing specified comorbid conditions than women without
      cancer, with different comorbidity profiles for those on tamoxifen versus
      aromatase inhibitors. Further research into the causes and mechanism of
      development and management of comorbidities after cancer is needed.

PMID- 29651410
TI  - Analysis of microRNAs Expression Profiles in Madin-Darby Bovine Kidney Cells
      Infected With Caprine Parainfluenza Virus Type 3.
AB  - Caprine parainfluenza virus type 3 (CPIV3) is a newly emerging pathogenic
      respiratory agent infecting both young and adult goats, and it was identified in
      eastern China in 2013. Cellular microRNAs (miRNAs) have been reported to be
      important modulators of the intricate virus-host interactions. In order to
      elucidate the role of miRNAs in madin-darby bovine kidney (MDBK) cells during
      CPIV3 infection. In this study, we performed high-throughput sequencing
      technology to analyze small RNA libraries in CPIV3-infected and mock-infected
      MDBK cells. The results showed that a total of 249 known and 152 novel candidate
      miRNAs were differentially expressed in MDBK cells after CPIV3 infection, and
      22,981 and 22,572 target genes were predicted, respectively. In addition, RT-qPCR
      assay was used to further confirm the expression patterns of 13 of these
      differentially expressed miRNAs and their mRNA targets. Functional annotation
      analysis showed these up- and downregulated target genes were mainly involved in
      MAPK signaling pathway, Jak-STAT signaling pathway, Toll-like receptor signaling
      pathway, p53 signaling pathway, focal adhesion, NF-kappa B signaling pathway, and
      apoptosis, et al. To our knowledge, this is the first report of the comparative
      expression of miRNAs in MDBK cells after CPIV3 infection. Our finding provides
      information concerning miRNAs expression profile in response to CPIV3 infection,
      and offers clues for identifying potential candidates for antiviral therapies
      against CPIV3.

PMID- 29651411
TI  - Leishmania Antigenuria to Predict Initial Treatment Failure and Relapse in
      Visceral Leishmaniasis/HIV Coinfected Patients: An Exploratory Study Nested
      Within a Clinical Trial in Ethiopia.
AB  - Background: Biomarkers predicting the risk of VL treatment failure and relapse in
      VL/HIV coinfected patients are needed. Nested within a two-site clinical trial in
      Ethiopia (2011-2015), we conducted an exploratory study to assess whether (1)
      levels of Leishmania antigenuria measured at VL diagnosis were associated with
      initial treatment failure and (2) levels of Leishmania antigenuria at the end of
      treatment (parasitologically-confirmed cure) were associated with subsequent
      relapse. Methods:Leishmania antigenuria at VL diagnosis and cure was determined
      using KAtex urine antigen test and graded as negative (0), weak/moderate (grade
      1+/2+) or strongly-positive (3+). Logistic regression and Kaplan-Meier methods
      were used to assess the association between antigenuria and (1) initial treatment
      failure, and (2) relapse over the 12 months after cure, respectively. Results:
      The analysis to predict initial treatment failure included sixty-three coinfected
      adults [median age: 30 years interquartile range (IQR) 27-35], median CD4 count:
      56 cells/MUL (IQR 38-113). KAtex results at VL diagnosis were negative in 11
      (17%), weak/moderate in 17 (27%) and strongly-positive in 35 (36%). Twenty (32%)
      patients had parasitologically-confirmed treatment failure, with a risk of
      failure of 9% (1/11) with KAtex-negative results, 0% (0/17) for KAtex 1+/2+ and
      54% (19/35) for KAtex 3+ results. Compared to KAtex-negative patients, KAtex 3+
      patients were at increased risk of treatment failure [odds ratio 11.9 (95% CI 1.4
      103.0); P: 0.025]. Forty-four patients were included in the analysis to predict
      relapse [median age: 31 years (IQR 28-35), median CD4 count: 116 cells/MUL (IQR
      95-181)]. When achieving VL cure, KAtex results were negative in 19 (43%),
      weak/moderate (1+/2+) in 10 (23%), and strongly positive (3+) in 15 patients
      (34%). Over the subsequent 12 months, eight out of 44 patients (18%) relapsed.
      The predicted 1-year relapse risk was 6% for KAtex-negative results, 14% for
      KAtex 1+/2+ and 42% for KAtex 3+ results [hazard ratio of 2.2 (95% CI 0.1-34.9)
      for KAtex 1+/2+ and 9.8 (95% CI 1.8-82.1) for KAtex 3+, compared to KAtex
      negative patients; P: 0.03]. Conclusion: A simple field-deployable Leishmania
      urine antigen test can be used for risk stratification of initial treatment
      failure and VL relapse in HIV-patients. A dipstick-format would facilitate field
      implementation.

PMID- 29651412
TI  - Editorial: Advances in Health-Care Transition for Patients With Childhood-Onset
      Chronic Diseases: International Perspectives.

PMID- 29651413
TI  - Are There Striking Differences in Outpatient Use of Antibiotics Between South
      Backa District, Serbia, and Some Scandinavian Countries?
AB  - There is little published information about antibiotic utilization in outpatients
      in Serbia. The objective of this study was to determine the amount and structure
      of outpatient antibiotic use in South Backa District (SBD) in Serbia, to assess
      prescibing quality of antibiotics and to compare with results from Scandinavian
      countries. Data on the antibiotic use were collected from all private and state
      owned pharmacies from January through March 2008 in SBD. Results were expressed
      as the number of defined daily doses/1,000 inhabitants/day. The drug utilization
      90% method was also used. Penicillins were the most frequently used antibiotic
      subgroup in SBD (35.20%), followed by cephalosporins (19.16%) and macrolides
      (13.18%). Thirteen drugs accounted for 90% of total antibiotics consumption
      (DU90% segment). The average cost/DDD within the DU90% segment was 0.95 euros,
      whereas the average cost/DDD beyond the DU90% segment was 1.89 euros, indicating
      that less expensive antibiotics were more frequently used. High use of
      ampicillin, third-generation cefalosporins, co-trimoxazole, and gentamicin, will
      aggravate the alarming problem of resistance in Serbia. Differences in the amount
      and structure of antibiotic consumption between SBD and Scandinavian countries
      indicate the need of updated national guidelines for rational antimicrobial drug
      use in Serbia.

PMID- 29651414
TI  - How Segregation Makes Us Fat: Food Behaviors and Food Environment as Mediators of
      the Relationship Between Residential Segregation and Individual Body Mass Index.
AB  - Objectives: Racial residential segregation affects food landscapes that dictate
      residents' food environments and is associated with obesity risk factors,
      including individual dietary patterns and behaviors. We examine if food behaviors
      and environments mediate the association between segregation and body mass index
      (BMI). Methods: Non-Hispanic Whites and Blacks living in the St. Louis and Kansas
      City metro regions from 2012 to 2013 were surveyed on dietary behaviors, food
      environment, and BMI (n = 1,412). These data were combined with the CDC's
      modified retail food environment index and 2012 American Community Survey data to
      calculate racial segregation using various evenness and exposure indices. Multi
      level mediation analyses were conducted to determine if dietary behavior and food
      environment mediate the association between racial residential segregation and
      individual BMI. Results: The positive association between racial segregation and
      individual BMI is partially mediated by dietary behaviors and fully mediated by
      food environments. Conclusion: Racial segregation (evenness and exposure) is
      associated with BMI, mediated by dietary behaviors and food environment. Elements
      of the food environment, which form the context for dietary behaviors, are
      potential targets for interventions to reduce obesity in residentially segregated
      areas.

PMID- 29651415
TI  - Longitudinal Changes in Physical Activity Level, Body Mass Index, and Oxygen
      Uptake Among Norwegian Adolescents.
AB  - Several studies have investigated activity levels among adolescents, but no study
      has examined longitudinal changes in physical activity (PA) level, body mass, and
      oxygen uptake among the same adolescents from the age of 14 to 19 years. The
      present study examined data from a research project that included a group of
      randomly selected students (N = 116) with objective measurements of PA
      (accelerometer data), self-reported PA level, and body mass and oxygen uptake
      during a 5-year period. The results show a significant decrease in the
      accelerometer-based PA level over time, from age 14 to 19. At 14 years of age,
      the minutes of moderate and/or vigorous PA was 66.7 min.day-1, but was less than
      half, at only 24.4 min.day-1, at 19 years of age. The self-reported activity data
      show a decrease in girls' general activity level over time, while boys' activity
      level during school breaks decreased strongly during the period: at age 14, 61%
      of the boys were classified as active, while at age 19, only 11% were physically
      active. Furthermore, body mass index increased during the period for both
      genders, while oxygen uptake decreased. Since both BMI and maximal oxygen uptake
      are important risk factors for future CVD, these findings point toward the
      importance of maintaining a high activity level during childhood and adolescence,
      in order to keep fit later in life.

PMID- 29651416
TI  - e-Bitter: Bitterant Prediction by the Consensus Voting From the Machine-Learning
      Methods.
AB  - In-silico bitterant prediction received the considerable attention due to the
      expensive and laborious experimental-screening of the bitterant. In this work, we
      collect the fully experimental dataset containing 707 bitterants and 592 non
      bitterants, which is distinct from the fully or partially hypothetical non
      bitterant dataset used in the previous works. Based on this experimental dataset,
      we harness the consensus votes from the multiple machine-learning methods (e.g.,
      deep learning etc.) combined with the molecular fingerprint to build the
      bitter/bitterless classification models with five-fold cross-validation, which
      are further inspected by the Y-randomization test and applicability domain
      analysis. One of the best consensus models affords the accuracy, precision,
      specificity, sensitivity, F1-score, and Matthews correlation coefficient (MCC) of
      0.929, 0.918, 0.898, 0.954, 0.936, and 0.856 respectively on our test set. For
      the automatic prediction of bitterant, a graphic program "e-Bitter" is developed
      for the convenience of users via the simple mouse click. To our best knowledge,
      it is for the first time to adopt the consensus model for the bitterant
      prediction and develop the first free stand-alone software for the experimental
      food scientist.

PMID- 29651418
TI  - Role of the Sympathetic Nervous System and Its Modulation in Renal Hypertension.
AB  - The kidneys are densely innervated with renal efferent and afferent nerves to
      communicate with the central nervous system. Innervation of major structural
      components of the kidneys, such as blood vessels, tubules, the pelvis, and
      glomeruli, forms a bidirectional neural network to relay sensory and sympathetic
      signals to and from the brain. Renal efferent nerves regulate renal blood flow,
      glomerular filtration rate, tubular reabsorption of sodium and water, as well as
      release of renin and prostaglandins, all of which contribute to cardiovascular
      and renal regulation. Renal afferent nerves complete the feedback loop via
      central autonomic nuclei where the signals are integrated and modulate central
      sympathetic outflow; thus both types of nerves form integral parts of the self
      regulated renorenal reflex loop. Renal sympathetic nerve activity (RSNA) is
      commonly increased in pathophysiological conditions such as hypertension and
      chronic- and end-stage renal disease. Increased RSNA raises blood pressure and
      can contribute to the deterioration of renal function. Attempts have been made to
      eliminate or interfere with this important link between the brain and the kidneys
      as a neuromodulatory treatment for these conditions. Catheter-based renal
      sympathetic denervation has been successfully applied in patients with resistant
      hypertension and was associated with significant falls in blood pressure and
      renal protection in most studies performed. The focus of this review is the
      neural contribution to the control of renal and cardiovascular hemodynamics and
      renal function in the setting of hypertension and chronic kidney disease, as well
      as the specific roles of renal efferent and afferent nerves in this scenario and
      their utility as a therapeutic target.

PMID- 29651417
TI  - Aging Mouse Models Reveal Complex Tumor-Microenvironment Interactions in Cancer
      Progression.
AB  - Mouse models and genetically engineered mouse models (GEMM) are essential
      experimental tools for the understanding molecular mechanisms within complex
      biological systems. GEMM are especially useful for inferencing phenocopy
      information to genetic human diseases such as breast cancer. Human breast cancer
      modeling in mice most commonly employs mammary epithelial-specific promoters to
      investigate gene function(s) and, in particular, putative oncogenes. Models are
      specifically useful in the mammary epithelial cell in the context of the complete
      mammary gland environment. Gene targeted knockout mice including conditional
      targeting to specific mammary cells can reveal developmental defects in mammary
      organogenesis and demonstrate the importance of putative tumor suppressor genes.
      Some of these models demonstrate a non-traditional type of tumor suppression
      which involves interplay between the tumor susceptible cell and its
      host/environment. These GEMM help to reveal the processes of cancer progression
      beyond those intrinsic to cancer cells. Furthermore, the, analysis of mouse
      models requires appropriate consideration of mouse strain, background, and
      environmental factors. In this review, we compare aging-related factors in mouse
      models for breast cancer. We introduce databases of GEMM attributes and colony
      functional variations.

PMID- 29651419
TI  - Management of Glioblastoma Multiforme in a Patient Treated With Ketogenic
      Metabolic Therapy and Modified Standard of Care: A 24-Month Follow-Up.
AB  - Few advances have been made in overall survival for glioblastoma multiforme (GBM)
      in more than 40 years. Here, we report the case of a 38-year-old man who
      presented with chronic headache, nausea, and vomiting accompanied by left partial
      motor seizures and upper left limb weakness. Enhanced brain magnetic resonance
      imaging revealed a solid cystic lesion in the right partial space suggesting GBM.
      Serum testing revealed vitamin D deficiency and elevated levels of insulin and
      triglycerides. Prior to subtotal tumor resection and standard of care (SOC), the
      patient conducted a 72-h water-only fast. Following the fast, the patient
      initiated a vitamin/mineral-supplemented ketogenic diet (KD) for 21 days that
      delivered 900 kcal/day. In addition to radiotherapy, temozolomide chemotherapy,
      and the KD (increased to 1,500 kcal/day at day 22), the patient received
      metformin (1,000 mg/day), methylfolate (1,000 mg/day), chloroquine phosphate (150
      mg/day), epigallocatechin gallate (400 mg/day), and hyperbaric oxygen therapy
      (HBOT) (60 min/session, 5 sessions/week at 2.5 ATA). The patient also received
      levetiracetam (1,500 mg/day). No steroid medication was given at any time. Post
      surgical histology confirmed the diagnosis of GBM. Reduced invasion of tumor
      cells and thick-walled hyalinized blood vessels were also seen suggesting a
      therapeutic benefit of pre-surgical metabolic therapy. After 9 months treatment
      with the modified SOC and complimentary ketogenic metabolic therapy (KMT), the
      patient's body weight was reduced by about 19%. Seizures and left limb weakness
      resolved. Biomarkers showed reduced blood glucose and elevated levels of urinary
      ketones with evidence of reduced metabolic activity (choline/N-acetylaspartate
      ratio) and normalized levels of insulin, triglycerides, and vitamin D. This is
      the first report of confirmed GBM treated with a modified SOC together with KMT
      and HBOT, and other targeted metabolic therapies. As rapid regression of GBM is
      rare following subtotal resection and SOC alone, it is possible that the response
      observed in this case resulted in part from the modified SOC and other novel
      treatments. Additional studies are needed to validate the efficacy of KMT
      administered with alternative approaches that selectively increase oxidative
      stress in tumor cells while restricting their access to glucose and glutamine.
      The patient remains in excellent health (Karnofsky Score, 100%) with continued
      evidence of significant tumor regression.

PMID- 29651421
TI  - When the Nose Doesn't Know: Canine Olfactory Function Associated With Health,
      Management, and Potential Links to Microbiota.
AB  - The impact of health, management, and microbiota on olfactory function in canines
      has not been examined in review. The most important characteristic of the
      detection canine is its sense of smell. Olfactory receptors are primarily located
      on the ethmoturbinates of the nasal cavity. The vomeronasal organ is an
      additional site of odor detection that detects chemical signals that stimulate
      behavioral and/or physiological changes. Recent advances in the genetics of
      olfaction suggest that genetic changes, along with the unique anatomy and airflow
      of the canine nose, are responsible for the macrosmia of the species.
      Inflammation, alterations in blood flow and hydration, and systemic diseases
      alter olfaction and may impact working efficiency of detection canines. The
      scientific literature contains abundant information on the potential impact of
      pharmaceuticals on olfaction in humans, but only steroids, antibiotics, and
      anesthetic agents have been studied in the canine. Physical stressors including
      exercise, lack of conditioning, and high ambient temperature impact olfaction
      directly or indirectly in the canine. Dietary fat content, amount of food per
      meal, and timing of meals have been demonstrated to impact olfaction in mice and
      dogs. Gastrointestinal (GI) microbiota likely impacts olfaction via bidirectional
      communication between the GI tract and brain, and the microbiota is impacted by
      exercise, diet, and stress. The objective of this literature review is to discuss
      the specific effects of health, management, and microbiota shifts on olfactory
      performance in working canines.

PMID- 29651422
TI  - Aspergillus-induced superoxide production by cystic fibrosis phagocytes is
      associated with disease severity.
AB  - Aspergillus fumigatus infects up to 50% of cystic fibrosis (CF) patients and may
      play a role in progressive lung disease. As cystic fibrosis transmembrane
      conductance regulator is expressed in cells of the innate immune system, we
      hypothesised that impaired antifungal immune responses play a role in CF-related
      Aspergillus lung disease. Peripheral blood mononuclear cells, polymorphonuclear
      cells (PMN) and monocytes were isolated from blood samples taken from CF patients
      and healthy volunteers. Live-cell imaging and colorimetric assays were used to
      assess antifungal activity in vitro. Production of reactive oxygen species (ROS)
      was measured using luminol-induced chemiluminescence and was related to clinical
      metrics as collected by case report forms. CF phagocytes are as effective as
      those from healthy controls with regards to phagocytosis, killing and restricting
      germination of A. fumigatus conidia. ROS production by CF phagocytes was up to
      four-fold greater than healthy controls (p<0.05). This effect could not be
      replicated in healthy phagocytes by priming with lipopolysaccharide or serum from
      CF donors. Increased production of ROS against A. fumigatus by CF PMN was
      associated with an increased number of clinical exacerbations in the previous
      year (p=0.007) and reduced lung function (by forced expiratory volume in 1 s)
      (p=0.014). CF phagocytes mount an intrinsic exaggerated release of ROS upon A.
      fumigatus stimulation which is associated with clinical disease severity.

PMID- 29651423
TI  - Zone of Polarizing Activity Regulatory Sequence Mutations/Duplications with
      Preaxial Polydactyly and Longitudinal Preaxial Ray Deficiency in the Phenotype: A
      Review of Human Cases, Animal Models, and Insights Regarding the Pathogenesis.
AB  - Clinicians and scientists interested in developmental biology have viewed
      preaxial polydactyly (PPD) and longitudinal preaxial ray deficiency (LPAD) as two
      different entities. Point mutations and duplications in the zone of polarizing
      activity regulatory sequence (ZRS) are associated with anterior ectopic
      expression of Sonic Hedgehog (SHH) in the limb bud and usually result in a PPD
      phenotype. However, some of these mutations/duplications also have LPAD in the
      phenotype. This unusual PPD-LPAD association in ZRS mutations/duplications has
      not been specifically reviewed in the literature. The author reviews this unusual
      entity and gives insights regarding its pathogenesis.

PMID- 29651420
TI  - The Human Replicative Helicase, the CMG Complex, as a Target for Anti-cancer
      Therapy.
AB  - DNA helicases unwind or rearrange duplex DNA during replication, recombination
      and repair. Helicases of many pathogenic organisms such as viruses, bacteria, and
      protozoa have been studied as potential therapeutic targets to treat infectious
      diseases, and human DNA helicases as potential targets for anti-cancer therapy.
      DNA replication machineries perform essential tasks duplicating genome in every
      cell cycle, and one of the important functions of these machineries are played by
      DNA helicases. Replicative helicases are usually multi-subunit protein complexes,
      and the minimal complex active as eukaryotic replicative helicase is composed of
      11 subunits, requiring a functional assembly of two subcomplexes and one protein.
      The hetero-hexameric MCM2-7 helicase is activated by forming a complex with Cdc45
      and the hetero-tetrameric GINS complex; the Cdc45-Mcm2-7-GINS (CMG) complex. The
      CMG complex can be a potential target for a treatment of cancer and the
      feasibility of this replicative helicase as a therapeutic target has been tested
      recently. Several different strategies have been implemented and are under active
      investigations to interfere with helicase activity of the CMG complex. This
      review focuses on the molecular function of the CMG helicase during DNA
      replication and its relevance to cancers based on data published in the
      literature. In addition, current efforts made to identify small molecules
      inhibiting the CMG helicase to develop anti-cancer therapeutic strategies were
      summarized, with new perspectives to advance the discovery of the CMG-targeting
      drugs.

PMID- 29651424
TI  - Energy Analysis of a Complementary Heating System Combining Solar Energy and Coal
      for a Rural Residential Building in Northwest China.
AB  - In order to utilize solar energy to meet the heating demands of a rural
      residential building during the winter in the northwestern region of China, a
      hybrid heating system combining solar energy and coal was built. Multiple
      experiments to monitor its performance were conducted during the winter in 2014
      and 2015. In this paper, we analyze the efficiency of the energy utilization of
      the system and describe a prototype model to determine the thermal efficiency of
      the coal stove in use. Multiple linear regression was adopted to present the dual
      function of multiple factors on the daily heat-collecting capacity of the solar
      water heater; the heat-loss coefficient of the storage tank was detected as well.
      The prototype model shows that the average thermal efficiency of the stove is
      38%, which means that the energy input for the building is divided between the
      coal and solar energy, 39.5% and 60.5% energy, respectively. Additionally, the
      allocation of the radiation of solar energy projecting into the collecting area
      of the solar water heater was obtained which showed 49% loss with optics and 23%
      with the dissipation of heat, with only 28% being utilized effectively.

PMID- 29651426
TI  - 4-Hydroxy-2-nonenal Alkylated and Peroxynitrite Nitrated Proteins Localize to the
      Fused Mitochondria in Malpighian Epithelial Cells of Type IV Collagen Drosophila
      Mutants.
AB  - Background. Human type IV collagenopathy is associated with mutations within the
      COL4A1 and to a less extent the COL4A2 genes. The proteins encoded by these genes
      form heterotrimers and are the highest molar ratio components of the ubiquitous
      basement membrane. The clinical manifestations of the COL4A1/A2 mutations are
      systemic affecting many tissues and organs among these kidneys. In order to
      uncover the cellular and biochemical alterations associated with aberrant type IV
      collagen, we have explored the phenotype of the Malpighian tubules, the secretory
      organ and insect kidney model, in col4a1 collagen gene mutants of the fruit fly
      Drosophila melanogaster. In Malpighian epithelial cells of col4a1 mutants, robust
      mitochondrial fusion indicated mutation-induced stress. Immunohistochemistry
      detected proteins nitrated by peroxynitrite that localized to the enlarged
      mitochondria and increased level of membrane peroxidation, assessed by the amount
      of proteins alkylated by 4-hydroxy-2-nonenal that similarly localized to the
      fused mitochondria. Nuclei within the Malpighian epithelium showed TUNEL
      positivity suggesting cell degradation. The results demonstrated that col4a1
      mutations affect the epithelia and, consequently, secretory function of the
      Malpighian tubules and provide mechanistic insight into col4a1 mutation
      associated functional impairments not yet reported in human patients and in mouse
      models with mutant COL4A1.

PMID- 29651425
TI  - MicroRNA-Mediated Regulation of HMGB1 in Human Hepatocellular Carcinoma.
AB  - High-mobility group box 1 (HMGB1) is a potential therapeutic target and novel
      biomarker in a variety of malignant tumors, including hepatocellular carcinoma
      (HCC). More recently, a number of microRNAs (miRNAs) are identified as a class of
      regulators for broad control of HMGB1-mediated biological actions in eukaryotic
      cells. In this review article we will describe representative miRNAs involved in
      regulating the HMGB1 signaling pathways in HCC cell lines and/or animal models.
      We also propose the possible mechanisms underlying the miRNA/HMGB1 axis and
      discuss the future clinical significance of miRNAs targeting HMGB1 molecule for
      HCC therapy.

PMID- 29651427
TI  - Do Mothers with Lower Socioeconomic Status Contribute to the Rate of All-Cause
      Child Mortality in Kazakhstan?
AB  - Background: This study aimed to explore whether or not mothers with higher
      educational and wealth status report lower rate of child mortality compared to
      those with less advantageous socioeconomic situation. Methods: Data used were
      cross-sectional and collected from Multiple Indicator Cluster Survey in
      Kazakhstan conducted in 2015. Subjects experiencing childbirth were 9278 women
      aging between 15 and 49 years. The associations between maternal education and
      household wealth status with child mortality were examined by multivariate
      analytical methods. Results: The overall prevalence of child mortality was 6.7%,
      with noticeable variations across the different regions. Compared with women who
      had the highest educational status, those with upper and lower secondary were
      1.47 and 1.89 times more likely to experience child death. Women in the lowest
      and second lowest wealth quintile had 2.74 and 2.68 times higher odds of
      experiencing child death compared with those in the richest wealth status
      households. Conclusions: Policy makers pay special attention to improving
      socioeconomic status of the mothers in an effort to reduce child mortality in the
      country. Women living in the disadvantaged regions with poor access to quality
      health care services should be regarded as a top priority.

PMID- 29651428
TI  - Effects and Mechanisms of Tastants on the Gustatory-Salivary Reflex in Human
      Minor Salivary Glands.
AB  - The effects and mechanisms of tastes on labial minor salivary gland (LMSG)
      secretion were investigated in 59 healthy individuals. Stimulation with each of
      the five basic tastes (i.e., sweet, salty, sour, bitter, and umami) onto the
      tongue induced LMSG secretion in a dose-dependent manner. Umami and sour tastes
      evoked greater secretion than did the other tastes. A synergistic effect of umami
      on LMSG secretion was recognized: a much greater increase in secretion was
      observed by a mixed solution of monosodium glutamate and inosine 5'-monophosphate
      than by each separate stimulation. Blood flow (BF) in the nearby labial mucosa
      also increased following stimulation by each taste except bitter. The BF change
      and LMSG secretion in each participant showed a significant positive correlation
      with all tastes, including bitter. Administration of cevimeline hydrochloride
      hydrate to the labial mucosa evoked a significant increase in both LMSG secretion
      and BF, while adrenaline, atropine, and pirenzepine decreased LMSG secretion and
      BF. The change in LMSG secretion and BF induced by each autonomic agent was
      significantly correlated in each participant. These results indicate that basic
      tastes can induce the gustatory-salivary reflex in human LMSGs and that
      parasympathetic regulation is involved in this mechanism.

PMID- 29651430
TI  - Biochemistry: Production of High-Added Value Biomolecules for Industrial Uses.

PMID- 29651431
TI  - Hsp90 Inhibition Reduces TLR5 Surface Expression and NF-kappaB Activation in
      Human Myeloid Leukemia THP-1 Cells.
AB  - Tumors highly express active heat shock protein 90 (Hsp90), which is involved in
      tumor survival and progression. Enhanced Toll-like receptor (TLR) 5 expression
      and signaling were reported to be associated with acute myeloid leukemia. In the
      present study, we investigated the possible modulatory effects of Hsp90
      inhibitors on TLR5 expression and signaling in the human myeloid leukemia cell
      line THP-1. Cells were pretreated with various concentrations of the Hsp90
      inhibitor geldanamycin (GA) or the Hsp70 inhibitor VER155008, followed by
      stimulation with bacterial flagellin. Flagellin-induced nuclear factor-kappaB (NF
      kappaB) activation was significantly reduced by treatment with GA or VER155008.
      To elucidate the underlying mechanism of this effect, mRNA and cell surface
      expression of TLR5 was examined. TLR5 mRNA expression was enhanced by both GA and
      VER155008, whereas cell surface expression of TLR5 was reduced by three different
      Hsp90 inhibitors, including GA, 17-(allylamino)-17-demethoxygeldanamycin, and
      radicicol, and an Hsp70 inhibitor. The inhibitory effect of Hsp90 inhibitors was
      much higher than that of Hsp70 inhibitor. Our results suggest that Hsp90
      inhibitors suppress TLR5 surface expression and activation of NF-kappaB in THP-1
      cells in response to TLR5 ligand, and these inhibitory effects may be associated
      with the possible mechanisms by which Hsp90 inhibitors suppress myeloid leukemia.

PMID- 29651432
TI  - Oxidative Stress Markers Patients with Parotid Gland Tumors: A Pilot Study.
AB  - Salivary gland tumors account for 3-6% of tumors of the head and neck. About 80%
      of salivary gland tumors occur in parotid glands. Oxidative stress (OS) is
      implicated in the origin, development, and whole-body effects of various tumors.
      There are no data on the occurrence of OS in the parotid gland tumors. The aim of
      this study was to ascertain if whole-body OS accompanies parotid gland tumors,
      based first of all on oxidative modifications of blood serum proteins and other
      markers of OS in the serum of the patients. The group studied included 17
      patients with pleomorphic adenoma, 9 patients with Warthin's tumor, 8 patients
      with acinic cell carcinoma, and 24 age-matched controls. We found increased
      concentration of interleukin 4 in patients with acinic cell carcinoma, decreased
      plasma thiols, increased AOPP concentration, and decreased FRAP of blood serum in
      all groups of the patients while protein oxidative modifications assessed
      fluorimetrically, protein carbonyls, protein nitration, malondialdehyde
      concentration, and serum ABTS*-scavenging capacity were unchanged. These data
      indicate the occurrence of OS in patients with parotid gland tumors and point to
      various sensitivities of OS markers.

PMID- 29651429
TI  - Therapeutic Potential of Thymoquinone in Glioblastoma Treatment: Targeting Major
      Gliomagenesis Signaling Pathways.
AB  - Glioblastoma multiforme (GBM) is one of the most devastating brain tumors with
      median survival of one year and presents unique challenges to therapy because of
      its aggressive behavior. Current treatment strategy involves surgery,
      radiotherapy, immunotherapy, and adjuvant chemotherapy even though optimal
      management requires a multidisciplinary approach and knowledge of potential
      complications from both the disease and its treatment. Thymoquinone (TQ), the
      main bioactive component of Nigella sativa L., has exhibited anticancer effects
      in numerous preclinical studies. Due to its multitargeting nature, TQ interferes
      in a wide range of tumorigenic processes and counteract carcinogenesis, malignant
      growth, invasion, migration, and angiogenesis. TQ can specifically sensitize
      tumor cells towards conventional cancer treatments and minimize therapy
      associated toxic effects in normal cells. Its potential to enter brain via nasal
      pathway due to volatile nature of TQ adds another advantage in overcoming blood
      brain barrier. In this review, we summarized the potential role of TQ in
      different signaling pathways in GBM that have undergone treatment with standard
      therapeutic modalities or with TQ. Altogether, we suggest further comprehensive
      evaluation of TQ in preclinical and clinical level to delineate its implied
      utility as novel therapeutics to combat the challenges for the treatment of GBM.

PMID- 29651433
TI  - Ratio of Injured Lung Volume Fraction in Prognosis Evaluation of Acute PQ
      Poisoning.
AB  - Although paraquat (PQ) concentrations are the most reliable prognosis predictors
      of PQ poisoning, these laboratory tests are not readily available in all
      hospitals. In this study, we proposed an imaging related parameter, that is, the
      ratio of injured lung volume fraction, for the prognosis evaluation of acute PQ
      poisoning based on the correlation between disease progress and lung imaging
      features. An artificial neural network was trained and then used to classify the
      injured and normal lung regions. The ratio of injured lung volume fraction was
      calculated from the injured lung volume fractions in the first and second CT
      scans after three-dimensional reconstruction. Parameters of blood tests were
      collected. A significant difference was observed with respect to the ratio of
      injured lung volume fraction between survivors and nonsurvivors (0.73 +/- 0.17
      versus 0.40 +/- 0.14, P < 0.001). No patients survived when the ratio of injured
      lung volume fraction was less than 0.3, while all patients survived as the ratio
      of injured lung volume fraction was greater than 0.8. Thus, the ratio of injured
      lung volume fraction may provide an alternative and informative measure for the
      prognosis of acute PQ poisoning.

PMID- 29651435
TI  - Which Kidney Transplant Recipients Can Benefit from the Initial Tacrolimus Dose
      Reduction?
AB  - Background: Observational data suggest that the fixed initial recommended
      tacrolimus (Tc) dosing (0.2 mg/kg/day) results in supratherapeutic drug levels in
      some patients during the early posttransplant period. The aim of the study was to
      analyze a wide panel of patient-related factors and their interactions which
      increase the risk for first Tc blood level > 15 ng/ml. Materials and Methods: We
      performed a retrospective analysis of 488 consecutive adult kidney transplant
      recipients who were initially treated with triple immunosuppressive regimen
      containing tacrolimus twice daily. The analysis included the first assessment of
      Tc trough blood levels and several demographic, anthropometric, laboratory, and
      comedication data. Results: The multiple logistic regression analysis showed that
      age > 55 years, BMI > 24.6 kg/m2, blood hemoglobin concentration > 9.5 g/dl, and
      the presence of anti-HCV antibodies independently increased the risk for first Tc
      level > 15 ng/ml. The relative risk (RR) for first tacrolimus level > 15 ng/ml
      was 1.88 (95% CI 1.35-2.64, p < 0.001) for patients with one risk factor and 2.81
      (2.02-3.89, p < 0.001) for patients with two risk factors. Conclusions: Initial
      tacrolimus dose reduction should be considered in older, overweight, or obese
      kidney transplant recipients and in subjects with anti-HCV antibodies. Moreover,
      dose reduction of tacrolimus is especially important in patients with coexisting
      multiple risk factors.

PMID- 29651434
TI  - Role of luxS in Stress Tolerance and Adhesion Ability in Lactobacillus plantarum
      KLDS1.0391.
AB  - Lactobacillus plantarum, a probiotic, has a high survival rate and high
      colonization ability in the gastrointestinal tract. Tolerance to the
      gastrointestinal environment and adhesion to intestinal epithelial cells by some
      Lactobacillus species (excluding L. plantarum) are related to luxS/AI-2. Here,
      the role of luxS in tolerance to simulated digestive juice (SDJ) and adhesion to
      Caco-2 cells by L. plantarum KLDS1.0391 (hereafter, KLDS1.0391) was investigated.
      The KLDS1.0391 luxS mutant strain was constructed by homologous recombination.
      When luxS was deleted, acid and bile salt tolerance and survival rates in SDJ
      significantly decreased (p < 0.05 for all). The ability of the luxS deletion
      strain to adhere to Caco-2 cells was markedly lower than that of the wild-type
      strain (p < 0.05). The ability of the luxS mutant strain to adhere (competition,
      exclusion, and displacement) to Escherichia coli ATCC 25922 was significantly
      lower than that of the wild-type strain (p < 0.05 for all). A significant
      decrease was noted only in the exclusion adhesion inhibition of the luxS mutant
      strain to Salmonella typhimurium ATCC 14028 (p < 0.05). These results indicate
      that the luxS gene plays an important role in the gastrointestinal environment
      tolerance and adhesion ability of KLDS1.0391.

PMID- 29651436
TI  - Multicomponent Exercise Improves Hemodynamic Parameters and Mobility, but Not
      Maximal Walking Speed, Transfer Capacity, and Executive Function of Older Type II
      Diabetic Patients.
AB  - The present study aimed to investigate the effects of a 6-month multicomponent
      exercise program (MCEP) on functional, cognitive, and hemodynamic parameters of
      older Type 2 diabetes mellitus (T2DM) patients. Moreover, additional analyses
      were performed to evaluate if T2DM patients present impaired adaptability in
      response to physical exercise when compared to nondiabetic volunteers. A total of
      72 T2DM patients and 72 age-matched healthy volunteers (CG) were recruited and
      submitted to functional, cognitive, and hemodynamic evaluations before and after
      six months of a MCEP. The program of exercise was performed twice a week at
      moderate intensity. Results indicate T2DM and nondiabetic patients present an
      increase in mobility (i.e., usual walking speed) after the MCEP. However,
      improvements in maximal walking speed, transfer capacity, and executive function
      were only observed in the CG. On the other hand, only T2DM group reveals a marked
      decline in blood pressure. In conclusion, data of the current study indicate that
      a 6-month MCEP improves mobility and reduce blood pressure in T2DM patients.
      However, maximal walking speed, transfer capacity, and executive function were
      only improved in CG, indicating that T2DM may present impaired adaptability in
      response to physical stimulus.

PMID- 29651437
TI  - Questions Frequently Asked of Healthcare Professionals: A 2-Year Data Survey
      Conducted at a Medical Center.
AB  - In this descriptive, retrospective study, we analyzed the types of questions
      posed by healthcare professionals to drug counselors at a medical center and the
      types of provision of pharmaceutical advice solicited to improve pharmaceutical
      care quality and establish clear directions for clinical pharmacist training. We
      collected 8,558 questions posed by healthcare professionals (physicians, 38%;
      pharmacists, 39%; nurses, 23%) from the electronic drug information record system
      from May 2013 to April 2015 in one medical center. Overall, 52% and 45% of calls
      came from outpatient and inpatient departments, respectively. Telephone was the
      main route of provision of pharmaceutical advice (total, 6,035 questions; 72%),
      and hospital/electronic formulary was the main reference type (43%). The top 10
      topics were dosage, alternatives, drug name, usage, adverse drug reactions,
      medication suggestion, drug compatibility, national health insurance criteria,
      mechanism, and indications. Pharmacological classification inquiries most
      frequently addressed antimicrobial agents (20%), and vancomycin was the top
      single drug. Finally, 67% of calls were completed in 5 minutes. Our results
      suggest that the systematic organization of issues into a searchable database
      would reduce inquiry durations and improve work efficiency. Furthermore, the
      availability of various search tools and methods would quickly provide healthcare
      professionals with provision of drug information needed to improve patient
      medication safety.

PMID- 29651438
TI  - Effect of Different Carbon Sources on Biosurfactants' Production by Three Strains
      of Lactobacillus spp.
AB  - The potential of three indigenous bacterial strains (Lactobacillus delbrueckii
      N2, Lactobacillus cellobiosus TM1, and Lactobacillus plantarum G88) for the
      production of biosurfactants using sugar cane molasses or glycerol as substrates
      was investigated through emulsifying, surface tension, and antimicrobial
      activities. The different biosurfactants produced with molasses as substrate
      exhibited high surface tension reduction from 72 mN/m to values ranged from 47.50
      +/- 1.78 to 41.90 +/- 0.79 mN/m and high emulsification index ranging from 49.89
      +/- 5.28 to 81.00 +/- 1.14%. Whatever the Lactobacillus strain or the substrate
      used, the biosurfactants produced showed antimicrobial activities against Candida
      albicans LV1, some pathogenic and/or spoilage Gram-positive and Gram-negative
      bacteria. The yields of biosurfactants with molasses (2.43 +/- 0.09 to 3.03 +/-
      0.09 g/L) or glycerol (2.32 +/- 0.19 to 2.82 +/- 0.05 g/L) were significantly (p
      < 0.05) high compared to those obtained with MRS broth as substrate (0.30 +/-
      0.02 to 0.51 +/- 0.09 g/L). Preliminary characterization of crude biosurfactants
      reveals that they are mainly glycoproteins and glycolipids with molasses and
      glycerol as substrate, respectively. Therefore, sugar cane molasses or glycerol
      can effectively be used by Lactobacillus strains as low-cost substrates to
      increase their biosurfactants production.

PMID- 29651439
TI  - Micrometer-Sized Titanium Particles Induce Aseptic Loosening in Rabbit Knee.
AB  - Wear debris induced aseptic loosening is the leading cause of total knee
      arthroplasty (TKA) failure. The complex mechanism of aseptic loosening has been a
      major issue for introducing effective prevention and treatment methods, so a
      simplified yet efficient rabbit model was established to address this concern
      with the use of micrometer-sized titanium particles. 20 New Zealand white rabbits
      were selected and divided into two groups (control = 10, study = 10). A TKA
      surgery was then performed for each of them, with implantation of a titanium rod
      prosthesis which was coated evenly with micrometer-sized titanium in the study
      group and nothing in the control group, into right femoral medullary cavity.
      After 12 weeks, all the animals were euthanized and X-ray analyses, H&E staining,
      Goldner Masson trichrome staining, Von Kossa staining, PCR, and Western blotting
      of some specific mRNAs and proteins in the interface membrane tissues around the
      prosthesis were carried out. The implantation of a titanium rod prosthesis coated
      with 20 MUm titanium particles into the femoral medullary cavity of rabbits
      caused continuous titanium particle stimulation around the prosthesis,
      effectively inducing osteolysis and aseptic loosening. Titanium particle-induced
      macrophages produce multiple inflammatory factors able to activate osteoclast
      differentiation through the OPG/RANKL/RANK signaling pathway, resulting in
      osteolysis while suppressing the function of osteoblasts and reducing bone
      ingrowth around the prosthesis. This model simulated the implantation and
      loosening process of an artificial prosthesis, which is an ideal etiological
      model to study the aseptic prosthetic loosening.

PMID- 29651442
TI  - Comment on "New Alternatives for Autoimmune Disease Treatments: Physicochemical
      and Clinical Comparability of Biosimilar Etanercept".

PMID- 29651440
TI  - Mast Cell, the Neglected Member of the Tumor Microenvironment: Role in Breast
      Cancer.
AB  - Mast cells are unique tissue-resident immune cells that secrete a diverse array
      of biologically active compounds that can stimulate, modulate, or suppress the
      immune response. Although mounting evidence supports that mast cells are
      consistently infiltrating tumors, their role as either a driving or an opposite
      force for cancer progression is still controversial. Particularly, in breast
      cancer, their function is still under discussion. While some studies have shown a
      protective role, recent evidence indicates that mast cells enhance blood and
      lymphatic vessel formation. Interestingly, one of the most important components
      of the mast cell cargo, the serine protease tryptase, is a potent angiogenic
      factor, and elevated serum tryptase levels correlate with bad prognosis in breast
      cancer patients. Likewise, histamine is known to induce tumor cell proliferation
      and tumor growth. In agreement, mast cell depletion reduces the size of mammary
      tumors and metastasis in murine models that spontaneously develop breast cancer.
      In this review, we will discuss the evidence supporting protumoral and
      antitumoral roles of mast cells, emphasizing recent findings placing mast cells
      as important drivers of tumor progression, as well as the potential use of these
      cells or their mediators as therapeutic targets.

PMID- 29651441
TI  - STAT1, IGF1, RAC1, and MDM2 Are Associated with Recurrence of Giant Cell Tumor of
      Bone.
AB  - Background: In our previous study, mouse double minute 2 homolog (MDM2), insulin
      like growth factor 1 (IGF1), signal transducer and activator of transcription 1
      (STAT1), and Rac family small GTPase 1 (RAC1) were correlated with the recurrence
      of giant cell tumor of bone (GCT). The aim of this study is to use a large cohort
      study to confirm the involvement of these four genes in GCT recurrence. Methods:
      The expression of these four genes was detected and compared between GCT patients
      with or without recurrence. The correlation between the expression of these four
      genes and clinical characteristics was evaluated. Protein-protein interaction
      (PPI) network was constructed for functional enrichment analysis. Results: It
      showed that the expression levels of MDM2, IGF1, STAT1, and RAC1 in GCT patients
      with recurrence were significantly higher than those in GCT patients without
      recurrence (P < 0.05). Multivariate logistic regression analysis suggested that
      several clinical characteristics may influence prognosis. A PPI network was
      constructed using the four genes as hub genes. Functional enrichment analysis
      showed that this network involves many important biological progress mediated by
      these four genes, including immune response. Conclusion: MDM2, IGF1, STAT1, and
      RAC1 are associated with GCT recurrence, which might serve as biomarkers for GCT
      recurrence.

PMID- 29651443
TI  - Immature Dendritic Cell Therapy Confers Durable Immune Modulation in an Antigen
      Dependent and Antigen-Independent Manner in Nonobese Diabetic Mice.
AB  - Dendritic cell (DC) immunotherapy has been effective for prevention of type 1
      diabetes (T1D) in NOD mice but fails to protect if initiated after active
      autoimmunity. As autoreactivity expands inter- and intramolecularly during
      disease progression, we investigated whether DCs unpulsed or pulsed with beta
      cell antigenic dominant determinants (DD), subdominant determinants (SD), and
      ignored determinants (ID) could prevent T1D in mice with advanced insulitis. We
      found that diabetes was significantly delayed by DC therapy. Of interest, DCs
      pulsed with SD or ID appeared to provide better protection. T lymphocytes from DC
      treated mice acquired spontaneous proliferating capability during in vitro
      culture, which could be largely eliminated by IL-2 neutralizing antibodies. This
      trend maintained even 29 weeks after discontinuing DC therapy and appeared
      antigen-independent. Furthermore, CD4+Foxp3+ T regulatory cells (Tregs) from DC
      treated mice proliferated more actively in vitro compared to the controls, and
      Tregs from DC-treated mice showed significantly enhanced immunosuppressive
      activities in contrast to those from the controls. Our study demonstrates that DC
      therapy leads to long-lasting immunomodulatory effects in an antigen-dependent
      and antigen-independent manner and provides evidence for peptide-based
      intervention during a clinically relevant window to guide DC-based immunotherapy
      for autoimmune diabetes.

PMID- 29651446
TI  - Autoimmunity in Reproductive Health and Pregnancy.

PMID- 29651445
TI  - Regulation of Immune Cell Functions by Metabolic Reprogramming.
AB  - Recent findings show that the metabolic status of immune cells can determine
      immune responses. Metabolic reprogramming between aerobic glycolysis and
      oxidative phosphorylation, previously speculated as exclusively observable in
      cancer cells, exists in various types of immune and stromal cells in many
      different pathological conditions other than cancer. The microenvironments of
      cancer, obese adipose, and wound-repairing tissues share common features of
      inflammatory reactions. In addition, the metabolic changes in macrophages and T
      cells are now regarded as crucial for the functional plasticity of the immune
      cells and responsible for the progression and regression of many pathological
      processes, notably cancer. It is possible that metabolic changes in the
      microenvironment induced by other cellular components are responsible for the
      functional plasticity of immune cells. This review explores the molecular
      mechanisms responsible for metabolic reprogramming in macrophages and T cells and
      also provides a summary of recent updates with regard to the functional
      modulation of the immune cells by metabolic changes in the microenvironment,
      notably the tumor microenvironment.

PMID- 29651447
TI  - Impaired Gal-9 Dysregulates the PBMC-Induced Th1/Th2 Imbalance in Abortion-Prone
      Matings.
AB  - Recurrent miscarriage is defined as the loss of 3 or more consecutive
      pregnancies; however, the underlying immunologic mechanisms that trigger
      pregnancy loss remain largely unelucidated. Galectin-9 (Gal-9) may modulate a
      variety of biologic functions and play an important role in Th1/Th2 immune
      deviation. To analyze the mechanism of Gal-9 in abortion, we used the classical
      abortion-prone mouse model (DBA/2-mated CBA/J mice) to detect the expression of
      Gal-9 at the maternal-fetal interface. We also mimicked the immune environment of
      pregnancy by culturing trophoblast cells with peripheral blood mononuclear cells
      (PBMCs) to explore how Gal-9 might be involved in the pathogenesis of abortion.
      We found that the expression levels of Gal-9 in abortion-prone matings were lower
      than that for controls. Using a coculture system, we detected a Th1 preponderance
      in the coculture from abortion-prone matings. Furthermore, Gal-9 blockade
      augmented the imbalance of Th1/Th2 immunity in abortion-prone matings by
      promoting the secretion of Th1-derived cytokines in coculture, while there was a
      Th2 preponderance when we administered recombinant Gal-9. In conclusion, our
      results suggest that the Gal-9 signal is important for the regulation of PBMC
      function toward a Th2 bias at the maternal-fetal interface, which is beneficial
      for the maintenance of a normal pregnancy.

PMID- 29651444
TI  - An Updated Review of the Molecular Mechanisms in Drug Hypersensitivity.
AB  - Drug hypersensitivity may manifest ranging from milder skin reactions (e.g.,
      maculopapular exanthema and urticaria) to severe systemic reactions, such as
      anaphylaxis, drug reactions with eosinophilia and systemic symptoms (DRESS)/drug
      induced hypersensitivity syndrome (DIHS), or Stevens-Johnson syndrome (SJS)/toxic
      epidermal necrolysis (TEN). Current pharmacogenomic studies have made important
      strides in the prevention of some drug hypersensitivity through the
      identification of relevant genetic variants, particularly for genes encoding drug
      metabolizing enzymes and human leukocyte antigens (HLAs). The associations
      identified by these studies are usually drug, phenotype, and ethnic specific. The
      drug presentation models that explain how small drug antigens might interact with
      HLA and T cell receptor (TCR) molecules in drug hypersensitivity include the
      hapten theory, the p-i concept, the altered peptide repertoire model, and the
      altered TCR repertoire model. The broad spectrum of clinical manifestations of
      drug hypersensitivity involving different drugs, as well as the various
      pathomechanisms involved, makes the diagnosis and management of it more
      challenging. This review highlights recent advances in our understanding of the
      predisposing factors, immune mechanisms, pathogenesis, diagnostic tools, and
      therapeutic approaches for drug hypersensitivity.

PMID- 29651449
TI  - On the performance of the noise power spectrum from the gain-corrected
      radiography images.
AB  - Fixed pattern noise due to nonuniform amplifier gains and scintillator
      sensitivity should be alleviated in radiography imaging to acquire low-noise x
      ray images from detectors. Here, the noise property of the detector is usually
      evaluated observing the noise power spectrum (NPS). A gain-correction scheme, in
      which uniformly illuminated images are averaged to design a gain map, can be
      applied to alleviate the fixed pattern noise problem. The normalized NPS (NNPS)
      of the gain-corrected image decreases as the number of images for the average
      increases and converges to an infimum, which can be achieved if the fixed pattern
      noise is completely removed. If we know the NNPS infimum of the detector, then we
      can determine the performance of the gain-corrected images compared with the
      achievable lower bound. We first construct an image-formation model considering
      the nonuniform gain and then consider two measurement methods based on
      subtraction and division to estimate the NNPS infimum of the detector. In order
      to obtain a high-precision NNPS infimum estimate, we consider a time-averaging
      method. For several flat-panel radiography detectors, we constructed the NNPS
      infimum measurements and compared them with NNPS values of the gain-corrected
      images. We observed that the NNPS values of the gain-corrected images approached
      the NNPS infimum as the number of images for the average increased.

PMID- 29651448
TI  - High-performance, inexpensive setup for simultaneous multisite recording of
      electrophysiological signals and mesoscale voltage imaging in the mouse cortex.
AB  - Simultaneous recording of optical and electrophysiological signals from multiple
      cortical areas may provide crucial information to expand our understanding of
      cortical function. However, the insertion of multiple electrodes into the brain
      may compromise optical imaging by both restricting the field of view and
      interfering with the approaches used to stabilize the specimen. Existing methods
      that combine electrophysiological recording and optical imaging in vivo implement
      either multiple surface electrodes, silicon probes, or a single electrode for
      deeper recordings. To address such limitation, we built a microelectrode array
      (hyperdrive, patent US5928143 A) compatible with wide-field imaging that allows
      insertion of up to 12 probes into a large brain area (8 mm diameter). The
      hyperdrive is comprised of a circle of individual microdrives where probes are
      positioned at an angle leaving a large brain area unobstructed for wide-field
      imaging. Multiple tetrodes and voltage-sensitive dye imaging were used for acute
      simultaneous registration of spontaneous and evoked cortical activity in
      anesthetized mice. The electrophysiological signals were used to extract local
      field potential (LFP) traces, multiunit, and single-unit spiking activity. To
      demonstrate our approach, we compared LFP and VSD signals over multiple regions
      of the cortex and analyzed the relationship between single-unit and global
      cortical population activities. The study of the interactions between cortical
      activity at local and global scales, such as the one presented in this work, can
      help to expand our knowledge of brain function.

PMID- 29651450
TI  - Automated contour tracking and trajectory classification of pelvic organs on
      dynamic MRI.
AB  - A method is presented to automatically track and segment pelvic organs on dynamic
      magnetic resonance imaging (MRI) followed by multiple-object trajectory
      classification to improve understanding of pelvic organ prolapse (POP). POP is a
      major health problem in women where pelvic floor organs fall from their normal
      position and bulge into the vagina. Dynamic MRI is presently used to analyze the
      organs' movements, providing complementary support for clinical examination.
      However, there is currently no automated or quantitative approach to measure the
      movement of the pelvic organs and their correlation with the severity of
      prolapse. In the proposed method, organs are first tracked and segmented using
      particle filters and [Formula: see text]-means clustering with prior information.
      Then, the trajectories of the pelvic organs are modeled using a coupled switched
      hidden Markov model to classify the severity of POP. Results demonstrate that the
      presented method can automatically track and segment pelvic organs with a Dice
      similarity index above 78% and Hausdorff distance of [Formula: see text] for 94
      tested cases while demonstrating correlation between organ movement and POP. This
      work aims to enable automatic tracking and analysis of multiple deformable
      structures from images to improve understanding of medical disorders.

PMID- 29651451
TI  - Toward dynamic lumbar puncture guidance using needle-based single-element
      ultrasound imaging.
AB  - Lumbar punctures (LPs) are interventional procedures that are used to collect
      cerebrospinal fluid. Since the target window is small, physicians have limited
      success conducting the procedure. The procedure is especially difficult for obese
      patients due to the increased distance between bone and skin surface. We propose
      a simple and direct needle insertion platform, enabling image formation by
      sweeping a needle with a single ultrasound element at the tip. The needle-shaped
      ultrasound transducer can not only sense the distance between the tip and a
      potential obstacle, such as bone, but also visually locate the structures by
      combining transducer location tracking and synthetic aperture focusing. The
      concept of the system was validated through a simulation that revealed robust
      image reconstruction under expected errors in tip localization. The initial
      prototype was built into a 14 G needle and was mounted on a holster equipped with
      a rotation shaft allowing one degree-of-freedom rotational sweeping and a
      rotation tracking encoder. We experimentally evaluated the system using a metal
      wire phantom mimicking high reflection bone structures and human spinal bone
      phantom. Images of the phantoms were reconstructed, and the synthetic aperture
      reconstruction improved the image quality. These results demonstrate the
      potential of the system to be used as a real-time guidance tool for improving
      LPs.

PMID- 29651452
TI  - Barnes Maze Procedure for Spatial Learning and Memory in Mice.
AB  - The Barnes maze is a dry-land based rodent behavioral paradigm for assessing
      spatial learning and memory that was originally developed by its namesake, Carol
      Barnes. It represents a well-established alternative to the more popular Morris
      Water maze and offers the advantage of being free from the potentially
      confounding influence of swimming behavior. Herein, the Barnes maze experimental
      setup and corresponding procedures for testing and analysis in mice are described
      in detail.

PMID- 29651453
TI  - Bacterial Cell Wall Precursor Phosphatase Assays Using Thin-layer Chromatography
      (TLC) and High Pressure Liquid Chromatography (HPLC).
AB  - Peptidoglycan encases the bacterial cytoplasmic membrane to protect the cell from
      lysis due to the turgor. The final steps of peptidoglycan synthesis require a
      membrane-anchored substrate called lipid II, in which the peptidoglycan subunit
      is linked to the carrier lipid undecaprenol via a pyrophosphate moiety. Lipid II
      is the target of glycopeptide antibiotics and several antimicrobial peptides, and
      is degraded by 'attacking' enzymes involved in bacterial competition to induce
      lysis. Here we describe two protocols using thin-layer chromatography (TLC) and
      high pressure liquid chromatography (HPLC), respectively, to assay the digestion
      of lipid II by phosphatases such as Colicin M or the LXG toxin protein TelC from
      Streptococcus intermedius. The TLC method can also monitor the digestion of
      undecaprenyl (pyro)phosphate, whereas the HPLC method allows to separate the di-,
      mono- or unphosphorylated disaccharide pentapeptide products of lipid II.

PMID- 29651454
TI  - Multiple episodes of extensive marine anoxia linked to global warming and
      continental weathering following the latest Permian mass extinction.
AB  - Explaining the ~5-million-year delay in marine biotic recovery following the
      latest Permian mass extinction, the largest biotic crisis of the Phanerozoic, is
      a fundamental challenge for both geological and biological sciences. Ocean redox
      perturbations may have played a critical role in this delayed recovery. However,
      the lack of quantitative constraints on the details of Early Triassic oceanic
      anoxia (for example, time, duration, and extent) leaves the links between oceanic
      conditions and the delayed biotic recovery ambiguous. We report high-resolution U
      isotope (delta238U) data from carbonates of the uppermost Permian to lowermost
      Middle Triassic Zal section (Iran) to characterize the timing and global extent
      of ocean redox variation during the Early Triassic. Our delta238U record reveals
      multiple negative shifts during the Early Triassic. Isotope mass-balance modeling
      suggests that the global area of anoxic seafloor expanded substantially in the
      Early Triassic, peaking during the latest Permian to mid-Griesbachian, the late
      Griesbachian to mid-Dienerian, the Smithian-Spathian transition, and the
      Early/Middle Triassic transition. Comparisons of the U-, C-, and Sr-isotope
      records with a modeled seawater PO43- concentration curve for the Early Triassic
      suggest that elevated marine productivity and enhanced oceanic stratification
      were likely the immediate causes of expanded oceanic anoxia. The patterns of
      redox variation documented by the U-isotope record show a good first-order
      correspondence to peaks in ammonoid extinctions during the Early Triassic. Our
      results indicate that multiple oscillations in oceanic anoxia modulated the
      recovery of marine ecosystems following the latest Permian mass extinction.

PMID- 29651455
TI  - Fossil scales illuminate the early evolution of lepidopterans and structural
      colors.
AB  - Lepidopteran scales exhibit remarkably complex ultrastructures, many of which
      produce structural colors that are the basis for diverse communication
      strategies. Little is known, however, about the early evolution of lepidopteran
      scales and their photonic structures. We report scale architectures from Jurassic
      Lepidoptera from the United Kingdom, Germany, Kazakhstan, and China and from
      Tarachoptera (a stem group of Amphiesmenoptera) from mid-Cretaceous Burmese
      amber. The Jurassic lepidopterans exhibit a type 1 bilayer scale vestiture: an
      upper layer of large fused cover scales and a lower layer of small fused ground
      scales. This scale arrangement, plus preserved herringbone ornamentation on the
      cover scale surface, is almost identical to those of some extant Micropterigidae.
      Critically, the fossil scale ultrastructures have periodicities measuring from
      140 to 2000 nm and are therefore capable of scattering visible light, providing
      the earliest evidence of structural colors in the insect fossil record. Optical
      modeling confirms that diffraction-related scattering mechanisms dominate the
      photonic properties of the fossil cover scales, which would have displayed
      broadband metallic hues as in numerous extant Micropterigidae. The fossil
      tarachopteran scales exhibit a unique suite of characteristics, including small
      size, elongate-spatulate shape, ridged ornamentation, and irregular arrangement,
      providing novel insight into the early evolution of lepidopteran scales.
      Combined, our results provide the earliest evidence for structural coloration in
      fossil lepidopterans and support the hypothesis that fused wing scales and the
      type 1 bilayer covering are groundplan features of the group. Wing scales likely
      had deep origins in earlier amphiesmenopteran lineages before the appearance of
      the Lepidoptera.

PMID- 29651457
TI  - Light-induced dynamic structural color by intracellular 3D photonic crystals in
      brown algae.
AB  - Natural photonic crystals are responsible for strong reflectance at selective
      wavelengths in different natural systems. We demonstrate that intracellular opal
      like photonic crystals formed from lipids within photosynthetic cells produce
      vivid structural color in the alga Cystoseira tamariscifolia. The reflectance of
      the opaline vesicles is dynamically responsive to environmental illumination. The
      structural color is present in low light-adapted samples, whereas higher light
      levels produce a slow disappearance of the structural color such that it
      eventually vanishes completely. Once returned to low-light conditions, the color
      re-emerges. Our results suggest that these complex intracellular natural photonic
      crystals are responsive to environmental conditions, changing their packing
      structure reversibly, and have the potential to manipulate light for roles beyond
      visual signaling.

PMID- 29651456
TI  - Systematic reconstruction of autism biology from massive genetic mutation
      profiles.
AB  - Autism spectrum disorder (ASD) affects 1% of world population and has become a
      pressing medical and social problem worldwide. As a paradigmatic complex genetic
      disease, ASD has been intensively studied and thousands of gene mutations have
      been reported. Because these mutations rarely recur, it is difficult to (i)
      pinpoint the fewer disease-causing versus majority random events and (ii)
      replicate or verify independent studies. A coherent and systematic understanding
      of autism biology has not been achieved. We analyzed 3392 and 4792 autism-related
      mutations from two large-scale whole-exome studies across multiple resolution
      levels, that is, variants (single-nucleotide), genes (protein-coding unit), and
      pathways (molecular module). These mutations do not recur or replicate at the
      variant level, but significantly and increasingly do so at gene and pathway
      levels. Genetic association reveals a novel gene + pathway dual-hit model, where
      the mutation burden becomes less relevant. In multiple independent analyses,
      hundreds of variants or genes repeatedly converge to several canonical pathways,
      either novel or literature-supported. These pathways define recurrent and
      systematic ASD biology, distinct from previously reported gene groups or
      networks. They also present a catalog of novel ASD risk factors including 118
      variants and 72 genes. At a subpathway level, most variants disrupt the pathway
      related gene functions, and in the same gene, they tend to hit residues extremely
      close to each other and in the same domain. Multiple interacting variants
      spotlight key modules, including the cAMP (adenosine 3',5'-monophosphate) second
      messenger system and mGluR (metabotropic glutamate receptor) signaling regulation
      by GRKs (G protein-coupled receptor kinases). At a superpathway level, distinct
      pathways further interconnect and converge to three biology themes: synaptic
      function, morphology, and plasticity.

PMID- 29651458
TI  - Differential expression of voltage-gated sodium channels in afferent neurons
      renders selective neural block by ionic direct current.
AB  - The assertion that large-diameter nerve fibers have low thresholds and small
      diameter fibers have high thresholds in response to electrical stimulation has
      been held in a nearly axiomatic regard in the field of neuromodulation and
      neuroprosthetics. In contrast to the short pulses used to evoke action
      potentials, long-duration ionic direct current has been shown to block neural
      activity. We propose that the main determinant of the neural sensitivity to
      direct current block is not the size of the axon but the types of voltage-gated
      sodium channels prevalent in its neural membrane. On the basis of the variants of
      voltage-gated sodium channels expressed in different types of neurons in the
      peripheral nerves, we hypothesized that the small-diameter nociceptive fibers
      could be preferentially blocked. We show the results of a computational model and
      in vivo neurophysiology experiments that offer experimental validation of this
      novel phenomenon.

PMID- 29651459
TI  - Evo-devo models of tooth development and the origin of hominoid molar diversity.
AB  - The detailed anatomical features that characterize fossil hominin molars figure
      prominently in the reconstruction of their taxonomy, phylogeny, and paleobiology.
      Despite the prominence of molar form in human origins research, the underlying
      developmental mechanisms generating the diversity of tooth crown features remain
      poorly understood. A model of tooth morphogenesis-the patterning cascade model
      (PCM)-provides a developmental framework to explore how and why the varying molar
      morphologies arose throughout human evolution. We generated virtual maps of the
      inner enamel epithelium-an indelibly preserved record of enamel knot arrangement
      in 17 living and fossil hominoid species to investigate whether the PCM explains
      the expression of all major accessory cusps. We found that most of the variation
      and evolutionary changes in hominoid molar morphology followed the general
      developmental rule shared by all mammals, outlined by the PCM. Our results have
      implications for the accurate interpretation of molar crown configuration in
      hominoid systematics.

PMID- 29651460
TI  - Isoprene photo-oxidation products quantify the effect of pollution on hydroxyl
      radicals over Amazonia.
AB  - Nitrogen oxides (NO x ) emitted from human activities are believed to regulate
      the atmospheric oxidation capacity of the troposphere. However, observational
      evidence is limited for the low-to-median NO x concentrations prevalent outside
      of polluted regions. Directly measuring oxidation capacity, represented primarily
      by hydroxyl radicals (OH), is challenging, and the span in NO x concentrations at
      a single observation site is often not wide. Concentrations of isoprene and its
      photo-oxidation products were used to infer the equivalent noontime OH
      concentrations. The fetch at an observation site in central Amazonia experienced
      varied contributions from background regional air, urban pollution, and biomass
      burning. The afternoon concentrations of reactive nitrogen oxides (NO y ),
      indicative of NO x exposure during the preceding few hours, spanned from 0.3 to
      3.5 parts per billion. Accompanying the increase of NO y concentration, the
      inferred equivalent noontime OH concentrations increased by at least 250% from
      0.6 * 106 to 1.6 * 106 cm-3. The conclusion is that, compared to background
      conditions of low NO x concentrations over the Amazon forest, pollution increased
      NO x concentrations and amplified OH concentrations, indicating the
      susceptibility of the atmospheric oxidation capacity over the forest to
      anthropogenic influence and reinforcing the important role of NO x in sustaining
      OH concentrations.

PMID- 29651461
TI  - Limiting parental interaction during vocal development affects acoustic call
      structure in marmoset monkeys.
AB  - Human vocal development is dependent on learning by imitation through social
      feedback between infants and caregivers. Recent studies have revealed that vocal
      development is also influenced by parental feedback in marmoset monkeys,
      suggesting vocal learning mechanisms in nonhuman primates. Marmoset infants that
      experience more contingent vocal feedback than their littermates develop
      vocalizations more rapidly, and infant marmosets with limited parental
      interaction exhibit immature vocal behavior beyond infancy. However, it is yet
      unclear whether direct parental interaction is an obligate requirement for proper
      vocal development because all monkeys in the aforementioned studies were able to
      produce the adult call repertoire after infancy. Using quantitative measures to
      compare distinct call parameters and vocal sequence structure, we show that
      social interaction has a direct impact not only on the maturation of the vocal
      behavior but also on acoustic call structures during vocal development. Monkeys
      with limited parental interaction during development show systematic differences
      in call entropy, a measure for maturity, compared with their normally raised
      siblings. In addition, different call types were occasionally uttered in motif
      like sequences similar to those exhibited by vocal learners, such as birds and
      humans, in early vocal development. These results indicate that a lack of
      parental interaction leads to long-term disturbances in the acoustic structure of
      marmoset vocalizations, suggesting an imperative role for social interaction in
      proper primate vocal development.

PMID- 29651462
TI  - Discovery of a hypersaline subglacial lake complex beneath Devon Ice Cap,
      Canadian Arctic.
AB  - Subglacial lakes are unique environments that, despite the extreme dark and cold
      conditions, have been shown to host microbial life. Many subglacial lakes have
      been discovered beneath the ice sheets of Antarctica and Greenland, but no
      spatially isolated water body has been documented as hypersaline. We use radio
      echo sounding measurements to identify two subglacial lakes situated in bedrock
      troughs near the ice divide of Devon Ice Cap, Canadian Arctic. Modeled basal ice
      temperatures in the lake area are no higher than -10.5 degrees C, suggesting that
      these lakes consist of hypersaline water. This implication of hypersalinity is in
      agreement with the surrounding geology, which indicates that the subglacial lakes
      are situated within an evaporite-rich sediment unit containing a bedded salt
      sequence, which likely act as the solute source for the brine. Our results reveal
      the first evidence for subglacial lakes in the Canadian Arctic and the first
      hypersaline subglacial lakes reported to date. We conclude that these previously
      unknown hypersaline subglacial lakes may represent significant and largely
      isolated microbial habitats, and are compelling analogs for potential ice-covered
      brine lakes and lenses on planetary bodies across the solar system.

PMID- 29651463
TI  - Anatomy of Mississippi Delta growth and its implications for coastal restoration.
AB  - The decline of several of the world's largest deltas has spurred interest in
      expensive coastal restoration projects to make these economically and
      ecologically vital regions more sustainable. The success of these projects
      depends, in part, on our understanding of how delta plains evolve over time
      scales longer than the instrumental record. Building on a new set of optically
      stimulated luminescence ages, we demonstrate that a large portion (~10,000 km2)
      of the late Holocene river-dominated Mississippi Delta grew in a radially
      symmetric fashion for almost a millennium before abandonment. Sediment was
      dispersed by deltaic distributaries that formed by means of bifurcations at the
      coeval shoreline and remained active throughout the life span of this landform.
      Progradation rates (100 to 150 m/year) were surprisingly constant, producing 6 to
      8 km2 of new land per year. This shows that robust rates of land building were
      sustained under preindustrial conditions. However, these rates are several times
      lower than rates of land loss over the past century, indicating that only a small
      portion of the Mississippi Delta may be sustainable in a future world with
      accelerated sea-level rise.

PMID- 29651464
TI  - HEx: A heterologous expression platform for the discovery of fungal natural
      products.
AB  - For decades, fungi have been a source of U.S. Food and Drug Administration
      approved natural products such as penicillin, cyclosporine, and the statins.
      Recent breakthroughs in DNA sequencing suggest that millions of fungal species
      exist on Earth, with each genome encoding pathways capable of generating as many
      as dozens of natural products. However, the majority of encoded molecules are
      difficult or impossible to access because the organisms are uncultivable or the
      genes are transcriptionally silent. To overcome this bottleneck in natural
      product discovery, we developed the HEx (Heterologous EXpression) synthetic
      biology platform for rapid, scalable expression of fungal biosynthetic genes and
      their encoded metabolites in Saccharomyces cerevisiae. We applied this platform
      to 41 fungal biosynthetic gene clusters from diverse fungal species from around
      the world, 22 of which produced detectable compounds. These included novel
      compounds with unexpected biosynthetic origins, particularly from poorly studied
      species. This result establishes the HEx platform for rapid discovery of natural
      products from any fungal species, even those that are uncultivable, and opens the
      door to discovery of the next generation of natural products.

PMID- 29651465
TI  - Fruit and Vegetable Consumption, and Physical Activity with Partner and Parental
      Status in African American Adults.
AB  - Objectives: The purpose of this study was to examine the relationships between
      partner and parental status and self-reported weekly fruit and vegetable
      consumption and level of physical activity in African American adults. Methods: A
      national sample of 2,370 African Americans participated in a telephone survey.
      Demographic data were collected and compared with fruit and vegetable consumption
      and physical activity responses. Results: When controlling for age (mean age =
      53.6 +/- 14.8 years) and education level, having children in the household was
      associated with greater fruit consumption. Being partnered was associated with
      moderate physical activity weekly for a higher percentage of women, and yet a
      shorter duration of minutes of moderate physical activity weekly for both women
      and men. Males (38.2% of the sample) reported being more physically active and
      females (61.8% of the sample) reported eating more fruits and vegetables.
      Conclusions: By understanding the role of partner and parental status in relation
      to healthy lifestyle for African Americans, family scientists and health care
      practitioners may be able to target the needs of this population to help prevent
      obesity and chronic illness.

PMID- 29651466
TI  - The Etiology and management of radiotherapy-induced fatigue.
AB  - Fatigue is one of the most common side-effects accompanying radiotherapy, but
      arguably the least understood. Radiotherapy-induced fatigue (RIF) is a clinical
      subtype of cancer treatment-related fatigue. It is described as a pervasive,
      subjective sense of tiredness persisting over time, interferes with activities of
      daily living, and is not relieved by adequate rest or sleep. RIF is one of the
      early side-effects and long-lasting for cancer patients treated with localized
      radiation. Although the underlying mechanisms of fatigue have been studied in
      several disease conditions, the etiology, mechanisms, and risk factors of RIF
      remain elusive, and this symptom remains poorly managed. The purpose of this
      paper is to review and discuss recent articles that defined, proposed biologic
      underpinnings and mechanisms to explain the pathobiology of RIF, as well as
      articles that proposed interventions to manage RIF. Understanding the mechanisms
      of RIF can describe promising pathways to identify at-risk individuals and
      identify potential therapeutic targets to alleviate and prevent RIF using a
      multimodal, multidisciplinary approach.

PMID- 29651467
TI  - Outcomes of Intraoperative OCT-Assisted Epiretinal Membrane Surgery from the
      PIONEER Study.
AB  - Purpose: To assess the retinal architecture changes which occur during epiretinal
      membrane (ERM) surgery, utilizing intraoperative optical coherence tomography
      (iOCT). Design: Prospective multi-surgeon single center study.
      Subjects/Participants: Subjects from the PIONEER iOCT study who underwent
      surgical intervention for management of ERM. Methods: All subjects underwent
      vitrectomy with ERM peeling with optional internal limiting membrane (ILM)
      peeling. Preoperative, intraoperative, and postoperative quantitative and
      qualitative OCT assessments were performed. Clinical characteristics including
      visual acuity outcomes, central subfield thickness and complications including
      ERM recurrence and need for reoperation were assessed at 3, 6 and 12 months
      following surgery for membrane peeling, as available. Main Outcome measures:
      Visual acuity outcomes, anatomic outcomes and complications including ERM
      recurrence. Microarchitectural alterations (i.e. retinal layer changes) following
      membrane peeling visualized with iOCT. Results: Seventy-six were identified and
      included in this analysis of clinical outcomes and quantitative OCT assessment.
      Twenty-four eyes were excluded due to insufficient intraoperative OCT quality for
      quantitative assessment. The mean preoperative VA measured 20/63. The mean
      postoperative VA at 3 months was 20/41 (p<0.0001), at 6 months measured 20/36 (p
      < 0.0001), and at 12 months measured 20/33 (p < 0.0001). Preoperative mean
      central subfield thickness (CST) was 426 microns. At 3 months, the mean CST
      improved to 377 microns (p < 0.0001). The 6-month postoperative CST was 367
      microns (p < 0.0001) and the 12-month postoperative CST measured 359 microns (p <
      0.0001). Immediately following membrane peeling, the distance between the retinal
      pigment epithelium and the ellipsoid zone as well as the distance between the
      retinal pigment epithelium and the cone outer segment tips/interdigitation zone
      significantly increased (p < 0.001). iOCT identified occult residual membranes in
      12% of cases and confirmed complete membrane peeling contrary to surgeon
      impression in 9% of cases. Reoperation was required for recurrent ERM in 1% of
      eyes. Conclusions: iOCT-assisted ERM peeling resulted in significant improvement
      in visual acuity, reduction in macular thickness, and low recurrence rate.
      Additional research is needed with randomized clinical trials to better define
      the comparative success rates of image-guided ERM surgery to standard surgical
      visualization techniques.

PMID- 29651468
TI  - Predicting Pathways into Criminal Behavior: The Intersection of Race, Gender,
      Poverty, Psychological Factors.
AB  - Women's incarceration rates have increased dramatically over recent years; with
      Black women's rates disproportionately and significantly higher than other races.
      Researchers have attempted to understand this criminal justice involvement
      disparity, and have suggested two major theoretical pathways Differential
      Involvement and Differential Selection Theories to explain these racial
      differences. We use the Differential Involvement Theory as a framework to discuss
      how the objective experience of economic disadvantage as measured by indicators
      of structural hardship including educational and employment under-attainment and
      the experience of psychological stress related to resource loss (because of this
      disadvantage) may explain women's engagement in criminal activity. In order to
      conceptualize psychological stress, we used Hobfoll's Conservation of Resource's
      (COR) Theory and measure. Next, we investigated the link between these factors
      and the degree (number of times incarcerated, number of months incarcerated in
      lifetime) of criminal behavior using baseline data collected from a NIH study
      that drew from a racially diverse sample of former substance abusing, criminally
      involved urban women. Results indicated potential racial differences in the
      perception of resource loss, and underscore the complex interaction of the
      experience of race, poverty, and the unique experience of stress on women's
      decision making and criminal justice involvement.

PMID- 29651469
TI  - Graphene-silver hybrid devices for sensitive photodetection in the ultraviolet.
AB  - The weak light-matter interaction in graphene can be enhanced with a number of
      strategies, among which sensitization with plasmonic nanostructures is
      particularly attractive. This has resulted in the development of graphene
      plasmonic hybrid systems with strongly enhanced photodetection efficiencies in
      the visible and the IR, but none in the UV. Here, we describe a silver
      nanoparticle-graphene stacked optoelectronic device that shows strong enhancement
      of its photoresponse across the entire UV spectrum. The device fabrication
      strategy is scalable and modular. Self-assembly techniques are combined with
      physical shadow growth techniques to fabricate a regular large-area array of 50
      nm silver nanoparticles onto which CVD graphene is transferred. The presence of
      the silver nanoparticles resulted in a plasmonically enhanced photoresponse as
      high as 3.2 A W-1 in the wavelength range from 330 nm to 450 nm. At lower
      wavelengths, close to the Van Hove singularity of the density of states in
      graphene, we measured an even higher responsivity of 14.5 A W-1 at 280 nm, which
      corresponds to a more than 10 000-fold enhancement over the photoresponse of
      native graphene.

PMID- 29651470
TI  - Growth of vertically aligned nanowires in metal-oxide nanocomposites: kinetic
      Monte-Carlo modeling versus experiments.
AB  - We employ kinetic Monte-Carlo simulations to study the growth process of metal
      oxide nanocomposites obtained via sequential pulsed laser deposition. Using Ni
      SrTiO3 (Ni-STO) as a model system, we reduce the complexity of the computational
      problem by choosing a coarse-grained approach mapping Sr, Ti and O atoms onto a
      single effective STO pseudo-atom species. With this ansatz, we scrutinize the
      kinetics of the sequential synthesis process, governed by alternating deposition
      and relaxation steps, and analyze the self-organization propensity of Ni atoms
      into straight vertically aligned nanowires embedded in the surrounding STO
      matrix. We finally compare the predictions of our binary toy model with
      experiments and demonstrate that our computational approach captures fundamental
      aspects of self-assembled nanowire synthesis. Despite its simplicity, our
      modeling strategy successfully describes the impact of relevant parameters like
      the concentration or laser frequency on the final nanoarchitecture of metal-oxide
      thin films grown via pulsed laser deposition.

PMID- 29651471
TI  - Effect of sulfonamidoethylenediamine substituents in RuII arene anticancer
      catalysts on transfer hydrogenation of coenzyme NAD+ by formate.
AB  - A series of neutral pseudo-octahedral RuII sulfonamidoethylenediamine complexes
      [(eta6-p-cym)Ru(N,N')Cl] where N,N' is N-(2-(R1,R2-amino)ethyl)-4
      toluenesulfonamide (TsEn(R1,R2)) R1,R2 = Me,H (1); Me,Me (2); Et,H (3); benzyl,H
      (Bz, 4); 4-fluorobenzyl,H (4-F-Bz, 5) or naphthalen-2-ylmethyl,H (Naph, 6), were
      synthesised and characterised including the X-ray crystal structure of 3. These
      complexes catalyse the reduction of NAD+ regioselectively to 1,4-NADH by using
      formate as the hydride source. The catalytic efficiency depends markedly on the
      steric and electronic effects of the N-substitutent, with turnover frequencies
      (TOFs) increasing in the order: 1 < 2 < 3, 6 < 4, 5, achieving a TOF of 7.7 h-1
      for 4 with a 95% yield of 1,4-NADH. The reduction rate was highest between pH*
      (deuterated solvent) 6 and 7.5 and improved with an increase in formate
      concentration (TOF of 18.8 h-1, 140 mM formate). The calculations suggested
      initial substitution of an aqua ligand by formate, followed by hydride transfer
      to RuII and then to NAD+, and indicated specific interactions between the aqua
      complex and both NAD+ and NADH, the former allowing a preorganisation involving
      interaction between the aqua ligand, formate anion and the pyridine ring of NAD+.
      The complexes exhibited antiproliferative activity towards A2780 human ovarian
      cancer cells with IC50 values ranging from 1 to 31 MUM, the most potent complex,
      [(eta6-p-cym)Ru(TsEn(Bz,H))Cl] (4, IC50 = 1.0 +/- 0.1 MUM), having a potency
      similar to the anticancer drug cisplatin. Co-administration with sodium formate
      (2 mM), increased the potency of all complexes towards A2780 cells by 20-36%,
      with the greatest effect seen for complex 6.

PMID- 29651472
TI  - Molecular structure and adsorption of dimethyl sulfoxide at the air/aqueous
      solution interface probed by non-resonant second harmonic generation.
AB  - In this study, non-resonant second harmonic generation (SHG) was used to
      investigate the molecular structure and adsorption of DMSO at the air/neat DMSO
      liquid and air/DMSO aqueous solution interfaces. The molecular orientation of
      interfacial DMSO as a function of the bulk DMSO concentration was investigated by
      quantitative polarization SHG analysis. For the air/neat DMSO liquid interface,
      the transition dipole moment of the S[double bond, length as m-dash]O group of
      DMSO is oriented 140 degrees  from the surface normal, where the S[double bond,
      length as m-dash]O group of DMSO is estimated to be 30 degrees  from the surface
      plane. The orientation of the S[double bond, length as m-dash]O group of
      interfacial DMSO is not dependent on the bulk DMSO concentration. Furthermore,
      the concentration-dependent SHG signal confirmed that the antiparallel double
      layer structure does not form at the air/DMSO water interface. The free energy of
      adsorption of DMSO at the air/DMSO aqueous solution interface was determined to
      be DeltaGads = -5.6 +/- 0.4 kJ mol-1.

PMID- 29651473
TI  - Microfluidic lung airway-on-a-chip with arrayable suspended gels for studying
      epithelial and smooth muscle cell interactions.
AB  - Chronic lung diseases (CLDs) are regulated by complex interactions between many
      different cell types residing in lung airway tissues. Specifically, interactions
      between airway epithelial cells (ECs) and airway smooth muscle cells (SMCs) have
      been shown in part to play major roles in the pathogenesis of CLDs, but the
      underlying molecular mechanisms are not well understood. To advance our
      understanding of lung pathophysiology and accelerate drug development processes,
      new innovative in vitro tissue models are needed that can reconstitute the
      complex in vivo microenvironment of human lung tissues. Organ-on-a-chip
      technologies have recently made significant strides in recapitulating
      physiological properties of in vivo lung tissue microenvironments. However, novel
      advancements are still needed to enable the study of airway SMC-EC communication
      with matrix interactions, and to provide higher throughput capabilities and
      manufacturability. We have developed a thermoplastic-based microfluidic lung
      airway-on-a-chip model that mimics the lung airway tissue microenvironment, and
      in particular, the interactions between SMCs, ECs, and supporting extracellular
      matrix (ECM). The microdevice is fabricated from acrylic using micromilling and
      solvent bonding techniques, and consists of three vertically stacked microfluidic
      compartments with a bottom media reservoir for SMC culture, a middle thin
      hydrogel layer, and an upper microchamber for achieving air-liquid interface
      (ALI) culture of the epithelium. A unique aspect of the design lies in the
      suspended hydrogel with upper and lower interfaces for EC and SMC culture,
      respectively. A mixture of type I collagen and Matrigel was found to promote EC
      adhesion and monolayer formation, and SMC adhesion and alignment. Optimal
      culturing protocols were established that enabled EC-SMC coculture for more than
      31 days. Epithelial monolayers displayed common morphological markers including
      ZO-1 tight junctions and F-actin cell cortices, while SMCs exhibited enhanced
      cell alignment and expression of alpha-SMA. The thermoplastic device construction
      facilitates mass manufacturing, allows EC-SMC coculture systems to be arrayed for
      increased throughput, and can be disassembled to allow extraction of the
      suspended gel for downstream analyses. This airway-on-a-chip device has potential
      to significantly advance our understanding of SMC-EC-matrix interactions, and
      their roles in the development of CLDs.

PMID- 29651474
TI  - Phase transition dynamics of single optically trapped aqueous potassium carbonate
      particles.
AB  - Fast dynamics (down to 10 ms) during exposure to changing relative humidity of
      single optically trapped K2CO3 particles were observed in the submicron to micron
      size range with time-resolved broadband light scattering and Raman spectroscopy.
      The study shows that complex multiple processes accompany efflorescence and
      deliquescence of unsupported aerosol particles. Efflorescence can occur in a
      single process in less than 10 ms (prompt) or proceed via multiple successive
      processes (multistep) that can last up to more than 10 seconds. The efflorescence
      relative humidity lies in the range of 9 to 25%. Raman spectra of the effloresced
      particles reveal that the final state of the particle is independent of the
      pathway. Deliquescence cycles start with an initial uptake of water followed by
      multiple complex processes which end at the deliquescence relative humidity (44
      50%). The study reveals that complex multiple processes during phase transitions
      are not limited to deposited particles where heterogeneous processes may occur or
      large particles in the upper micrometer size range as previously observed.

PMID- 29651475
TI  - Intermolecular hydrogen bonds in water@IL supramolecular complexes.
AB  - The role of small amounts of water in ionic liquids (ILs), namely, 1-n-butyl-2,3
      dimethylimidazolium imidazolate (BMMI.Im), 2-methylimidazolate (BMMI.MeIm), and
      pyrazolate (BMMI.Pyr), is examined using NMR spectroscopy and density functional
      theory (DFT) calculations. The nuclear Overhauser effect (NOE) indicates that a
      water molecule is trapped inside the ionic network, keeping the ion pair in
      contact through strong H-bonds involving the hydrogen atoms of water and the
      nitrogen atoms of the IL anions to give a guest@host supramolecular structure.
      The formation of the H2O@IL pair complex with different ILs combined with the
      strong hydrogen bond strength within the complex is responsible for the selective
      H/D exchange reactions at the imidazolium C2-Me and ketone Calpha positions.

PMID- 29651476
TI  - Correction: Synthesis of pyrrolidine-3-carboxylic acid derivatives via asymmetric
      Michael addition reactions of carboxylate-substituted enones.
AB  - Correction for 'Synthesis of pyrrolidine-3-carboxylic acid derivatives via
      asymmetric Michael addition reactions of carboxylate-substituted enones' by Feng
      Yin et al., Org. Biomol. Chem., 2017, 15, 6089-6092.

PMID- 29651477
TI  - Metal-free C(sp2)-H functionalization of azoles: K2CO3/I2-mediated oxidation,
      imination, and amination.
AB  - The direct C2-H oxidation and imination of a wide variety of azoles was achieved
      by using a commercially available simple K2CO3/I2 reagent combination. The
      iodinated azole adduct, produced via the in situ generation of N-heterocyclic
      carbene, is the key intermediate for C2-H oxidation, imination, and amination of
      azoles. Significantly, these reactions proceed under mild conditions with high to
      excellent yields, are scalable to large quantity and exhibit a broad substrate
      scope. Interestingly, this direct C2-H imination method allowed us to access
      various pharmacologically active N6-alkyl or N6-aryl substituted
      benzimidazoquinazolinone scaffolds through intramolecular C-H imination in a
      sequential one-pot reaction.

PMID- 29651478
TI  - Halogen-like properties of the Al13 cluster mimicking astatine.
AB  - Astatine-211 is considered to be one of the most promising alpha-emitters in
      targeted alpha therapy (TAT). However, its development has been hindered by its
      not so well understood chemistry. Hence, any attempt to understanding it better
      is imperative. Here, we show through DFT calculations that the neutral endohedral
      Al13 cluster follows a reactivity pattern very similar to At, more than any other
      halogen. The halogen and alkali bonding with Al13 and At presented a strong
      similarity in their charge transfer processes. Moreover, upon the interchange of
      At with Al13, we found a stable configuration of the compound corresponding to
      the astatination of aryliodonium salts, which have been considered as possible
      precursors for the synthesis of 211At-labeled tracers. Our results provide
      promising proof of concept that the Al13 cluster mimics the behaviour of At and
      might help in better understanding its chemistry and in streamlining the chemical
      processes of radiolabeling biomolecules.

PMID- 29651479
TI  - Spatially dependent dose rate in liquid cell transmission electron microscopy.
AB  - The use of liquid cell electron microscopy as a quantitative probe of
      nanomaterial structures and reactions requires an accurate understanding of how
      the sample is altered by the imaging electron beam. In particular, changes in the
      chemical environment due to beam-induced radiolysis can strongly affect processes
      such as solution-phase nanocrystal synthesis or electrochemical deposition. It is
      generally assumed that beam effects are uniform throughout the irradiated liquid.
      Here we show that for a liquid cell filled with water, the inevitable presence of
      interfaces between water and the surrounding surfaces causes a spatial variation
      in the energy absorbed by the water near the walls. The mechanism for this effect
      is that the walls act as a source of secondary and backscattered electrons which
      diffuse and deposit energy in the water nearby. This increased dose rate then
      changes the local concentrations of radiolysis species. We quantify and compare
      the effects for different materials used in practical liquid cells. We show that
      the dose rate can increase by several times within tens of nanometers of a
      water/Au interface, locally increasing the concentrations of species such as the
      hydrated electron. We discuss the implications for materials processes that are
      typically triggered at the solid-liquid interface.

PMID- 29651480
TI  - Self-powered photogalvanic phosphorene photodetectors with high polarization
      sensitivity and suppressed dark current.
AB  - High polarization sensitivity, suppressed dark current and low energy consumption
      are all desirable device properties for photodetectors. In this work, we propose
      phosphorene-based photodetectors that are driven using photogalvanic effects
      (PGEs). The inversion symmetry of pristine phosphorene is broken using either
      application of an out-of-plane gate voltage or a heterostructure that is composed
      of the original phosphorene and blue phosphorene. The potential asymmetry enables
      PGEs under illumination by polarized light. Quantum transport calculations show
      that robust photocurrents are indeed generated by PGEs under a zero external bias
      voltage because of the broken inversion symmetry. These results indicate that the
      proposed photodetector is self-powered. In addition, the zero bias voltage
      eliminates the dark currents that are caused by application of an external bias
      voltage to traditional photodetectors. High polarization sensitivity to both
      linearly and circularly polarized light can also be realized, with extinction
      ratios ranging up to 102. The photoresponse of the proposed phosphorene/blue
      phosphorene heterostructure can be greatly enhanced by gating and is several
      orders of magnitude higher than that in gated phosphorene.

PMID- 29651481
TI  - Ultrasonically synthesized organic liquid-filled chitosan microcapsules: part 1:
      tuning physical & functional properties.
AB  - This study reports the synthesis of tetradecane-filled chitosan microcapsules in
      acetic acid aqueous solutions using high intensity ultrasound at 20 kHz. The
      size, size distribution, and stability of microcapsules were tuned by varying the
      concentration of acetic acid from 0.2% to 25% v/v. After long-time storage at
      room temperature (more than 3 months), the microcapsules maintained their shell
      core structure where the volume of the microcapsules at 0.2% acetic acid
      concentration increased by 8.3% due to leaking and coalescence. Microcapsules
      were consistently spherical and had a smooth shell surface, however, their shell
      thickness varied with acetic acid concentration. The relaxation behavior of
      individual microcapsules to an applied constant stress was measured by atomic
      force microscopy (AFM) to probe the shell strength and extent of crosslinking.
      The effect of acetic acid on the relative viscosity of chitosan aqueous solutions
      played a major role in microcapsule size control at low acid concentrations. With
      constant addition of acetic acid, amino groups in chitosan chains were acetylated
      partially under ultrasonic irradiation. This reduced the amphiphilicity of the
      shell material and therefore influenced the size, size distribution, stability
      and mechanical strength of the microcapsules. Apart from the acetylation effect,
      the counter-ion effect and the formation of covalent bond crosslinks also made
      contributions to the formation of stable chitosan microcapsules.

PMID- 29651482
TI  - Ultrasonically synthesized organic liquid-filled chitosan microcapsules: part 2:
      characterization using AFM (atomic force microscopy) and combined AFM-confocal
      laser scanning fluorescence microscopy.
AB  - Atomic Force Microscopy (AFM) is used to measure the stiffness and Young's
      modulus of individual microcapsules that have a chitosan cross-linked shell
      encapsulating tetradecane. The oil filled microcapsules were prepared using a one
      pot synthesis via ultrasonic emulsification of tetradecane and crosslinking of
      the chitosan shell in aqueous solutions of acetic acid. The concentration of
      acetic acid in aqueous solutions of chitosan was varied from 0.2% to 25% v/v. The
      effect of acetic acid concentration and size of the individual microcapsules on
      the strength was probed. The deformations and forces required to rupture the
      microcapsules were also measured. Three dimensional deformations of microcapsules
      under large applied loads were obtained by the combination of Laser Scanning
      Confocal Microscopy (LSCM) with Atomic Force Microscopy (AFM). The stiffness, and
      hence the modulus, of the microcapsules was found to decrease with an increase in
      size with the average stiffness ranging from 82 to 111 mN m-1 and average Young's
      modulus ranging from 0.4 to 6.5 MPa. The forces required to rupture the
      microcapsules varied from 150 to 250 nN with deformations of the microcapsules up
      to 62 to 110% relative to their radius, respectively. Three dimensional images
      obtained using laser scanning confocal microscopy showed that the microcapsules
      retained their structure and shape after being subjected to large deformations
      and subsequent removal of the loads. Based on the above observations, the oil
      filled chitosan crosslinked microcapsules are an ideal choice for use in the food
      and pharmaceutical industries as they would be able to withstand the process
      conditions encountered.

PMID- 29651483
TI  - Superprotonic conduction through one-dimensional ordered alkali metal ion chains
      in a lanthanide-organic framework.
AB  - Although no evident hydrogen-bond network appears, an ultrahigh proton
      conductivity of 2.91 * 10-2 S cm-1 at 363 K and 90% RH with an ultralow
      activation energy of 0.10 eV was observed in an anionic lanthanide-organic
      framework Na2[Eu(SDB)2(COO)].0.375DMF.0.4H2O (1); both values approach the
      records among all reported proton-conducting MOF materials. This suggests that
      the proton conduction process in 1 is reminiscent of the Grotthuss mechanism,
      which together reveals an effective proton transportation pathway associated with
      aligned Na+ and their coordinated water.

PMID- 29651484
TI  - Rieske non-heme iron-dependent oxygenases catalyse diverse reactions in natural
      product biosynthesis.
AB  - Covering: up to the end of 2017 The roles played by Rieske non-heme iron
      dependent oxygenases in natural product biosynthesis are reviewed, with
      particular focus on experimentally characterised examples. Enzymes belonging to
      this class are known to catalyse a range of transformations, including oxidative
      carbocyclisation, N-oxygenation, C-hydroxylation and C-C desaturation. Examples
      of such enzymes that have yet to be experimentally investigated are also briefly
      described and their likely functions are discussed.

PMID- 29651485
TI  - Structural signature and transition dynamics of Sb2Te3 melt upon fast cooling.
AB  - Crystalline Sb2Te3 is widely studied due to its important applications in memory
      materials and topological insulators. The liquid and amorphous structures of this
      compound as well as the dynamics upon quenching, however, are yet to be fully
      understood. In this work, we have systematically studied the dynamical properties
      and local structure of Sb2Te3 at different temperatures using ab initio molecular
      dynamics simulations. The calculated structure factors agree well with the
      experimental results. The atomic number density and mean-squared displacement as
      a function of temperature clearly indicate three states as the temperature
      decreases, namely, melt, undercooled liquid and glass state, respectively. By
      analyzing the chemical environments and bond-angle distribution functions, we
      demonstrate that the most probable short-range motifs in the Sb2Te3 system are
      defective octahedrons, and they are connected with each other via four-fold
      rings. This interesting structural feature may be responsible for the high
      fragility and easy phase transition upon glass forming that is applied in memory
      devices.

PMID- 29651486
TI  - Coexistence of distinct intramolecular electron transfer pathways in
      polyoxometalate based molecular triads.
AB  - Polyoxometalate (POM)-associated charge-separated states, formed by the
      photoinduced oxidation of a covalently attached photosensitizer and reduction of
      the POM, have attracted much attention due to the remarkable catalytic properties
      of the reduced POMs. However, short lifetimes of the POM-associated charge
      separated state, which in some cases lead to the backward electron transfer being
      more rapid than the formation of the charge-separated state itself, are generally
      observed. Recently, we reported on the first example of a relative long-lived
      (tau = 470 ns) charge-separated state in a Ru(ii) bis(terpyridine)-POM molecular
      dyad. In this manuscript, further studies on extended molecular structures - two
      molecular triads - which contain an additional electron donor, phenothiazine
      (PTZ) or pi-extended tetrathiafulvalene (exTTF), are discussed. We show that the
      excitation of the photosensitizer leads to the population of two distinct MLCT
      states, which differ in the distribution of excess electron density on the two
      distinct tpy ligands. These two MLCT states decay separately and, thus,
      constitute the starting points for distinct intramolecular electron-transfer
      pathways leading to the simultaneous population of two partially charge-separated
      states, i.e. PTZ+-Ru(tpy)2--POM and PTZ-RuIII(tpy)2-POM-. These independent decay
      pathways are unaffected by the choice of the electron donor. Thus, the initial
      charge distribution within the coordination environment of the photocenter
      determines the nature of the subsequent (partially) charge separated state that
      is formed in the triads. These results might open new avenues to design molecular
      interfaces, in which the directionality of electron transfer can be tuned by the
      choice of initial excitation.

PMID- 29651487
TI  - The organic-2D transition metal dichalcogenide heterointerface.
AB  - Since the first isolation of graphene, new classes of two-dimensional (2D)
      materials have offered fascinating platforms for fundamental science and
      technology explorations at the nanometer scale. In particular, 2D transition
      metal dichalcogenides (TMD) such as MoS2 and WSe2 have been intensely
      investigated due to their unique electronic and optical properties, including
      tunable optical bandgaps, direct-indirect bandgap crossover, strong spin-orbit
      coupling, etc., for next-generation flexible nanoelectronics and nanophotonics
      applications. On the other hand, organics have always been excellent materials
      for flexible electronics. A plethora of organic molecules, including donors,
      acceptors, and photosensitive molecules, can be synthesized using low cost and
      scalable procedures. Marrying the fields of organics and 2D TMDs will bring
      benefits that are not present in either material alone, enabling even better,
      multifunctional flexible devices. Central to the realization of such devices is a
      fundamental understanding of the organic-2D TMD interface. Here, we review the
      organic-2D TMD interface from both chemical and physical perspectives. We discuss
      the current understanding of the interfacial interactions between the organic
      layers and the TMDs, as well as the energy level alignment at the interface,
      focusing in particular on surface charge transfer and electronic screening
      effects. Applications from the literature are discussed, especially in
      optoelectronics and p-n hetero- and homo-junctions. We conclude with an outlook
      on future scientific and device developments based on organic-2D TMD
      heterointerfaces.

PMID- 29651488
TI  - A full color photonic polymer, rewritable with a liquid crystal ink.
AB  - A printable and rewritable photonic polymer coating has been fabricated from a
      cholesteric liquid crystal. Full color images can be patterned in polymer
      coatings by using a liquid crystal ink. The printed patterns can be erased and
      rewritten multiple times, making these coatings interesting as rewritable papers.

PMID- 29651489
TI  - How changes in interfacial pH lead to new voltammetric features: the case of the
      electrochemical oxidation of hydrazine.
AB  - The electrochemical oxidation of hydrazine was investigated in strongly and
      weakly pH buffered solutions to reveal the role of buffer capacity in proton
      electron transfer redox reactions. In sufficiently buffered solutions, a single
      voltammetric feature was observed. However, increasing the hydrazine
      concentration (or, equivalently, moving to an insufficiently buffered solution)
      gave rise to a second voltammetric feature. These results are rationalised with a
      conceptually simple model and finite element simulations. We demonstrate that the
      new voltammetric feature is caused by a large change in the pH at the electrode
      surface as the reaction proceeds. Importantly, we show that the occurrence of
      additional voltammetric features are general for proton-electron transfer
      reactions in insufficiently buffered solutions, and should not be confused with
      changes in the reaction mechanism.

PMID- 29651490
TI  - Palladium-catalyzed aerobic regio- and stereo-selective olefination reactions of
      phenols and acrylates via direct dehydrogenative C(sp2)-O cross-coupling.
AB  - An efficient olefination protocol for the oxidative dehydrogenation of phenols
      and acrylates has been achieved using a palladium catalyst and O2 as the sole
      oxidant. This reaction exhibits high regio- and stereo-selectivity (E-isomers)
      with moderate to excellent isolated yields and a wide substrate scope (32
      examples) including ethyl vinyl ketone and endofolliculina.

PMID- 29651491
TI  - Unifying theoretical framework for deciphering the oxygen reduction reaction on
      platinum.
AB  - Rapid conversion of oxygen into water is crucial to the operation of polymer
      electrolyte fuel cells and other emerging electrochemical energy technologies.
      Chemisorbed oxygen species play double-edged roles in this reaction, acting as
      vital intermediates on one hand and site-blockers on the other. Any attempt to
      decipher the oxygen reduction reaction (ORR) must first relate the formation of
      oxygen intermediates to basic electronic and electrostatic properties of the
      catalytic surface, and then link it to parameters of catalyst activity. An
      approach that accomplishes this feat will be of great utility for catalyst
      materials development and predictive model formulation of electrode operation.
      Here, we present a theoretical framework for the multiple interrelated surface
      phenomena and processes involved, particularly, by incorporating the double-layer
      effects. It sheds light on the roles of oxygen intermediates and gives out the
      Tafel slope and exchange current density as continuous functions of electrode
      potential. Moreover, it develops the concept of a rate determining term, which
      should replace the concept of a rate determining step for multielectron
      reactions, and offers a new perspective on the volcano relation of the ORR.

PMID- 29651492
TI  - The mechanochemical Scholl reaction - a solvent-free and versatile graphitization
      tool.
AB  - Herein, we report on the mechanochemical Scholl reaction of dendritic
      oligophenylene precursors to produce benchmark nanographenes such as hexa-peri
      hexabenzocoronene (HBC), triangular shaped C60 and expanded C222 under solvent
      free conditions. The solvent-free approach overcomes the bottleneck of solubility
      limitation in this well-known and powerful reaction. The mechanochemical approach
      allows tracking the reaction process by in situ pressure measurements. The
      quality of produced nanographenes has been confirmed by MALDI-TOF mass
      spectrometry and UV-Vis absorption spectroscopy. This approach paves the way
      towards gram scale and environmentally benign synthesis of extended nanographenes
      and possibly graphene nanoribbons suitable for application in carbon based
      electronics or energy applications.

PMID- 29651493
TI  - Marangoni convection at electrogenerated hydrogen bubbles.
AB  - Electrolytic gas evolution is a fundamental phenomenon occurring in a large
      number of industrial applications. In these processes gas bubbles are formed at
      the electrode from a supersaturated solution. Since dissolved gases can change
      the surface tension, a gas concentration gradient may cause the surface tension
      to vary locally at the interface of the gas bubble. Surface tension gradients may
      also form due to temperature gradients generated by ohmic heating of the
      electrolyte. In both cases, the resulting shear stress imposes a convection in
      the electrolyte and the gas bubble (Marangoni effect). This phenomenon may
      influence the entire electrolytic gas evolution process, e.g., by an enhanced
      mass transfer. In this study, the first evidence of the Marangoni convection near
      growing hydrogen bubbles, generated by water electrolysis, is provided.
      Microscopic high speed imaging was applied to study the evolution of single
      hydrogen bubbles at a microelectrode. The convection near the interface of the
      growing bubble was measured by using a time-resolved Particle Tracking
      Velocimetry (PTV) technique. The results indicate a clear correlation between the
      magnitude of the Marangoni convection and the electric current.

PMID- 29651494
TI  - Oxygen-reduction catalysis of N-doped carbons prepared via heat treatment of
      polyaniline at over 1100  degrees C.
AB  - Advanced catalysts for the oxygen reduction reaction based on N-doped carbon
      materials have been designed via pyrolysis of polyaniline at temperatures above
      1100  degrees C. The detailed characterization and computational calculations
      suggest that the conversion from pyridine to quaternary N in the edge position at
      high temperatures is responsible for the outstanding activity.

PMID- 29651495
TI  - Highly effective electrosynthesis of hydrogen peroxide from oxygen on a redox
      active cationic covalent triazine network.
AB  - Direct electrosynthesis of hydrogen peroxide (H2O2) by oxygen reduction is a
      green and safe strategy to replace the traditional anthraquinone process. Herein,
      we have designed a two-dimensional redox-active cationic covalent triazine
      network to be used directly as a cost-effective metal-free electrocatalyst for
      the oxygen reduction reaction (ORR) to form H2O2. Such a dicationic 2D polymer
      possesses a porous structure with pore diameters of 2-10 nm and a total N content
      of 13.3 wt%. The electron paramagnetic resonance experiment confirms the
      reduction of a viologen-based polymer to radical cations and the subsequent
      generation of superoxygen radicals. The radical characteristics and high N
      content within this polymer are the essential for the efficient ORR via a two
      electron pathway. As a result, the present electrocatalyst exhibits a high ORR
      activity and excellent H2O2 selectivity (~85%), thus providing a feasible
      possibility of designing highly selective metal-free electrocatalysts for
      electrocatalytic production of H2O2 from O2.

PMID- 29651496
TI  - Plasmonic sphere-on-plane systems with semiconducting polymer spacer layers.
AB  - The optical properties of metal-film-coupled nanoparticles (NPs) are highly
      sensitive to physical and optical interactions between the NPs and the spacer
      medium in the gap between the NP and metal film. Here, we investigate the
      physical and optical interactions between gold NPs (AuNPs) and semiconducting
      conjugated polymer thin-film spacers in a "sphere-on-plane" type metal-film
      coupled NP system, and their influence on the plasmonic scattering of individual
      AuNPs. We choose two different conjugated polymers: one with an absorption
      spectrum that is resonant with the plasmonic modes of the AuNPs and another that
      is non-resonant. By correlating dark-field back-scattering optical images with
      topographic atomic force microscope images, we find that partial embedding of the
      AuNPs occurs in both conjugated polymers to different extents. This can lead to
      partial quenching of certain plasmonic scattering modes, which results in a
      change of the back-scattering colors from the AuNPs. Pronounced, red-shifted
      scattering is observed due to deep embedding of the AuNPs, particularly for
      thicker conjugated polymer spacers that have resonant absorption with the
      plasmonic modes of the AuNPs. Polarization-controlled defocused dark-field
      imaging is employed to visualize the emergence of horizontally-polarized
      scattering modes upon embedding of AuNPs into the conjugated polymer spacer.
      These results demonstrate the importance of nanoparticle-spacer physical
      interactions to the control of the color and polarization of coupled plasmonic
      modes in nanoparticle-film systems relevant.

PMID- 29651497
TI  - A rationally assembled graphene nanoribbon/graphene framework for high volumetric
      energy and power density Li-ion batteries.
AB  - High volumetric energy and power densities are crucial for Li-ion batteries,
      which are however hindered by the loose structure and/or insufficient
      conductivity of conventional electrode laminates. Herein, an efficiently
      conductive framework of graphene nanoribbons (GNRs) and graphene (G) is
      rationally constructed to wrap LiFePO4 (LFP) into a binder-free dense electrode
      by a coupling technique of spray deposition and vacuum filtration. The spray
      ensures a uniform mixing of LFP, G and GNRs, meanwhile the vacuum filtration
      leads to a dense packing of the mixture. With only 2 wt% of G and GNRs, the
      LFP/GNR/G electrode delivers a high rate capability and a stable (dis)charge
      cycling performance under high LFP loading conditions. Moreover, the dense
      LFP/GNR/G electrode exhibits superior volumetric properties among all the
      reported LFP electrodes on the basis of the entire electrode volume, including a
      Li storage capacity of 318 A h L-1, an energy density of 1020 W h L-1 and a power
      density of 5.1 kW L-1 at 5C rate. This unique assembly strategy and the electrode
      structure pave a new way for high-volumetric-performance batteries.

PMID- 29651498
TI  - Hand, Foot and Mouth Disease and Echovirus 3: A Comment to Hogsberg & Bygum.

PMID- 29651499
TI  - AKI biomarkers are poor discriminants for subsequent need for renal replacement
      therapy, but do not disqualify them yet.

PMID- 29651501
TI  - Fullerene C60 in Atmospheric Aerosol and Its Relationship to Combustion
      Processes.
AB  - Fullerenes are emerging pollutants, and it is essential to determine and quantify
      these compounds to assess environmental risk and environmental flows. The goal of
      this work was to determine the fullerene C60 emission levels in the atmospheric
      aerosol and their relationship with combustion processes. To measure the
      concentration, a fullerene C60 extraction method with toluene was optimized in
      air samples using ultrasound, followed by analysis using high-pressure, liquid
      chromatography-diode array detector-mass spectrometry. This method has been
      applied to outdoor and indoor environmental samples collected in different places
      in Vitoria-Gasteiz (Spain), with diverse environmental characteristics, as well
      as at the exhaust outlets of different vehicles with and without catalytic
      converters. The maximum concentration of fullerene C60 present in the outdoor
      samples was 2.27 pg/m3, and the maximum concentration was 10.50 pg/m3 in indoor
      environments. The air samples collected at the exhaust outlets of vehicles
      without catalytic converters showed fullerene C60 concentrations above 170 pg/m3,
      while in the case of vehicles with catalytic converters, the detected
      concentration of fullerene C60 was lower than the limit of quantification.

PMID- 29651502
TI  - Historical Records and Source Apportionment of Polycyclic Aromatic Hydrocarbons
      Over the Past 100 Years in Dianchi Lake, a Plateau Lake in Southwest China.
AB  - Two sediment cores were collected from Dianchi Lake, a plateau lake in Southwest
      China, to study the temporal trends and to investigate the sources of sedimentary
      deposited polycyclic aromatic hydrocarbon. The SigmaPAH16 concentration in the
      two sediment cores ranged from 172.5 to 2244.8 ng/g and from 211.4 to 1777.8
      ng/g, with mean values of 1106.2 and 865.1 ng/g, respectively. Three temporal
      trends for the SigmaPAH16 concentration and the composition of PAHs in Dianchi
      Lake all showed three typical changing stages: (1) slight changes in deeper
      segments before the 1950s; (2) a rapid increase in PAH concentrations between the
      1960s and 1990s; and (3) a slight reduction from the 1990s onward. These trends
      differ from those observed in developed countries due to differences in the
      timing of industrialization and urbanization processes. According to the results
      of the molecular ratios and principal component analysis, the PAH deposition was
      dominated by coal combustion, wood combustion, and vehicle emissions before and
      after the 1960s, respectively.

PMID- 29651500
TI  - Outcome of endovascular treatment for acute basilar artery occlusion in the
      modern era: a single institution experience.
AB  - PURPOSE: The beneficial effect of endovascular treatment (EVT) for patients with
      acute basilar artery occlusion (ABAO) remains uncertain. The purpose of the
      present study was to evaluate clinical outcome of EVT for patients with ABAO and
      analyze prognostic factors of good outcome. METHODS: From our prospectively
      established database, we reviewed all patients with ABAO receiving EVT during
      January 2014 to December 2016. Baseline characteristics and outcomes were
      evaluated. Favorable functional outcome was defined as modified Rankin Scale
      score of 0 to 3 assessed at 3-month follow-up. The association between clinical
      and procedural characteristics and functional outcome was assessed. RESULTS: Of
      the 68 patients included, 50 patients (73.5%) received mechanical thrombectomy
      with stent retriever device. Successful reperfusion (thrombolysis in cerebral
      infarction grades 2b-3) was achieved in 61 patients (89.7%). Overall favorable
      functional outcome was reached by 31 patients (45.6%). In univariate analysis,
      Glasgow Coma Scale sum score, baseline National Institutes of Health stroke scale
      score (NIHSS), and baseline glycemia level were identified predicting good
      clinical outcome. Multivariate analysis showed that lower NIHSS was the only
      independent risk factor of favorable functional outcome (OR 0.832; 95% CI, 0.715
      0.968; p = 0.018). No difference of favorable outcomes was observed between the
      subgroups of time to EVT < 6 h and ? 6 h. CONCLUSIONS: Data in the present study
      suggests that EVT for ABAO patients should be reasonable within 24 h of symptom
      onset. The most important factor determining clinical outcome is initial stroke
      severity.

PMID- 29651503
TI  - Biorefineries: A Short Introduction.
AB  - The terms bioeconomy and biorefineries are used for a variety of processes and
      developments. This short introduction is intended to provide a delimitation and
      clarification of the terminology as well as a classification of current
      biorefinery concepts. The basic process diagrams of the most important
      biorefinery types are shown.

PMID- 29651504
TI  - Reactors for Microbial Electrobiotechnology.
AB  - From the first electromicrobial experiment to a sophisticated microbial
      electrochemical process - it all takes place in a reactor. Whereas the reactor
      design and materials used strongly influence the obtained results, there are no
      common platforms for MES reactors. This is a critical convention gap, as cross
      comparison and benchmarking among MES as well as MES vs. conventional
      biotechnological processes is needed. Only knowledge driven engineering of MES
      reactors will pave the way to application and commercialization. In this chapter
      we first assess the requirements on reactors to be used for bioelectrochemical
      systems as well as potential losses caused by the reactor design. Subsequently,
      we compile the main types and designs of reactors used for MES so far, starting
      from simple H-cells to stirred tank reactors. We conclude with a discussion on
      the weaknesses and strengths of the existing types of reactors for
      bioelectrochemical systems that are scored on design criteria and draw
      conclusions for the future engineering of MES reactors.

PMID- 29651505
TI  - The role of psychiatric status on pediatric extremity fractures: a prospective
      analysis.
AB  - PURPOSE: The aim of the study was to investigate the relationship between
      attention deficit and hyperactivity disorder (ADHD), anxiety, and depression with
      pediatric extremity fractures. METHODS: Between November 2014 and November 2016,
      consecutive 138 patients with pediatric extremity fractures were prospectively
      investigated in terms of the tendency to anxiety, depression, or ADHD in the
      study group. Consecutive 168 non-trauma patients who were admitted to general
      pediatrics outpatient clinic were included the control group. Patients were
      performed with Turgay DSM-IV-Based Child and Adolescent Behavior Disorders
      Screening and Rating Scale-Parents Form (T-DSM-IV S), The Screen for Child
      Anxiety-Related Emotional Disorders (SCARED), and The Children's Depression
      Inventory (CDI). RESULTS: There were not any significant differences between
      study and control groups regarding the age, gender distribution, economical
      level, or previous psychiatric admission rates (p > 0.05). In the study group,
      the previous ADHD history and previous fracture history were significantly higher
      than the control group (p < 0.05). In the study group, the severity of depressive
      signs and anxiety were significantly higher than the control group (p = 0.000 and
      p = 0.019; respectively). Regarding the previous fracture history, conduct
      disorder and tendency to depression were significantly higher in the study group
      (p = 0.001 and p = 0.011; respectively). CONCLUSIONS: The signs of ADHD, anxiety,
      and depression were determined to be higher in children with extremity fractures
      compared with the non-traumatic population. In patients with especially
      behavioral problems and depressive signs, directing to the child and adolescent
      psychiatrists will be protective to prevent re-fractures and high-energy traumas.

PMID- 29651506
TI  - Characteristics on 621 cases of craniomaxillofacial fractures.
AB  - PURPOSE: This study examined a single center's experience with regards to
      etiology and distribution of fractures treated from July 2015 to August 2016 in
      Shanghai, China. METHODS: The medical records of 621 patients with
      craniomaxillofacial fractures were reviewed. Patient notes and radiographic
      images were analyzed for detailed injury data. Age, gender, etiology, and site of
      fracture were examined. Chi-square test was used to analyze the causes of single
      and multiple fractures. p < 0.05 was considered statistically significant.
      RESULTS: This study included 426 male and 195 female with a male-to-female ratio
      of 2.18:1, among which 28.3% were between 19 and 29 years (n = 176). In all the
      fracture sites, orbit was most commonly involved (n = 319, 51.4%). Traffic
      accidents (n = 304, 49%) were the most common cause of injury in this study,
      while ground-level falls were the most common cause of injury in children (n =
      19, 41.3%). The probability of multiple fractures due to falling from height
      (88.6%, p < 0.05) and traffic accidents (73.3%, p < 0.05) were significantly
      higher than that of other injuries. Orbital fractures have the highest surgical
      rate (n = 288, 90.3%). CONCLUSION: Craniomaxillofacial fractures predominantly
      occur in young men, due to traffic accidents. Orbit was involved in most cases.
      Falling from height and traffic accidents is more likely to cause multiple
      fractures.

PMID- 29651508
TI  - Correction to: Using self-reports of pain and other variables to distinguish
      between older women with back pain due to vertebral fractures and those with back
      pain due to degenerative changes.
AB  - This article was originally published under a CC BY-NC-ND 4.0 license, but has
      now been made available under a CC BY 4.0 license. The PDF and HTML versions of
      the paper have been modified accordingly.

PMID- 29651507
TI  - Efficacy and side effects of baclofen and the novel GABAB receptor positive
      allosteric modulator CMPPE in animal models for alcohol and cocaine addiction.
AB  - RATIONALE: Preclinical studies suggest that the GABAB receptor is a potential
      target for treatment of substance use disorders. However, recent clinical trials
      report adverse effects in patients treated with the GABAB receptor agonist
      baclofen and even question efficacy. How can the discrepancy between preclinical
      and clinical findings be explained? OBJECTIVE: To test efficacy and adverse
      effects of baclofen and the novel GABAB positive allosteric modulator (PAM) CMPPE
      in rat addiction models, which were developed in accordance with DSM. METHODS: We
      used a well-characterized rat model of long-term alcohol consumption with
      repeated deprivation phases that result in compulsive alcohol drinking in a
      relapse situation, and a rat model of long-term intravenous cocaine self
      administration resulting in key symptoms of addictive behavior. We tested
      repeated baclofen (0, 1, and 3 mg/kg; i.p.) and CMPPE doses (0, 10, and 30 mg/kg;
      i.p.) in relapse-like situations, in either alcohol or cocaine addicted-like
      rats. RESULTS: Baclofen produced a weak anti-relapse effect at the highest dose
      in alcohol addicted-like rats, and this effect was mainly due to the treatment
      induced sedation. CMPPE had a better profile, with a dose-dependent reduction of
      relapse-like alcohol drinking and without any signs of sedation. The cue-induced
      cocaine-seeking response was completely abolished by both compounds. CONCLUSION:
      Positive allosteric modulation of the GABAB receptor provides efficacy, and no
      observable side effects in relapse behavior whereas baclofen may cause, not only
      sedation, but also considerable impairment of food intake or metabolism. However,
      targeting GABAB receptors may be effective in reducing certain aspects of
      addictive-like behavior, such as cue-reactivity.

PMID- 29651509
TI  - The role of previous falls in major osteoporotic fracture prediction in
      conjunction with FRAX in older Chinese men and women: the Mr. OS and Ms. OS
      cohort study in Hong Kong.
AB  - Falls are a major concern in terms of fracture risk. Although awareness rising
      for the absence of falls in the FRAX algorithm, our study only identified the
      independent predictive role of previous recurrent falls and their better
      conjunction use with FRAX for major osteoporotic fracture prediction in older
      Chinese men.

PMID- 29651510
TI  - [Vomiting and collapse of a 28-year-old male long distance runner in middle
      European Summer].
AB  - BACKGROUND: Hyperthermia often ends fatally and must therefore be promptly
      recognized and adequately treated. CASE: A 28-year-old man participated in a long
      distance race (3 km) on a hot summer day (28  degrees C). The runner collapsed,
      had to vomit but continued the run and reached the finish. Neurologically, the
      patient presented with intermittent cerebral seizures. External cooling batteries
      were immediately applied and cold infusions were started. The patient was
      admitted to the intensive care unit of the university hospital (body temperature
      40.2  degrees C). After a few hours, a manifest disseminated intravascular
      coagulopathy developed with multiple organ failure. It took 12 l of volume
      replacement, 8 units of fresh frozen plasma and 2 units of erythrocyte
      concentrates in the first 12 h to stabilize the patient. Although with the help
      of forced external cooling and application of cold infusions, the body
      temperature could be lowered to 38  degrees C by the next morning, the overall
      situation of the patient continued to deteriorate. Despite dialysis and massive
      substitution of coagulation factors, the patient could not be sufficiently
      stabilized and died of brain edema. CONCLUSION: Not only the old or young
      children are subject to the potential danger of a fatal heat stroke but also
      young athletic persons after normal sports activities (3 km run). Cooling must be
      started immediately and the patient must be hospitalized as a vital emergency. If
      hemostasis fails due to the heat-related loss of hepatogenic protein synthesis, a
      viscious circle begins, which, as in the reported case, is irreversible despite
      maximum therapy and substitution.

PMID- 29651511
TI  - [Follow-up care for gastrointestinal tumors].
AB  - The follow-up care of patients with gastrointestinal cancer is poorly defined.
      Prospective trials showing that regular follow-up care is advantageous are
      largely lacking. Follow-up is primarily based on symptom evaluation, as well as
      on an assessment of nutritional status and the need for psycho-oncological care.
      Whereas the evidence for regular endoscopic follow-up is well defined in early
      cancers, the role of follow-up care in advanced cancers is less well defined.
      This deficit is mainly due to the lack of therapeutic consequences in the case of
      recurrence. In such cases, cure is only rarely possible, and most studies have
      failed to demonstrate a survival benefit following standardized follow-up care of
      these patients. However, in view of the evolving treatment options in recurrent
      disease and the success of recurrent colorectal cancer treatment, it seems
      reasonable to define the current status of follow-up care for patients with
      gastrointestinal cancers.

PMID- 29651512
TI  - [Stabilization of the chest wall with plate osteosynthesis].

PMID- 29651513
TI  - [Chest trauma from a surgical perspective].
AB  - Patients with multiple injuries in particular frequently also suffer from chest
      trauma. During the initial phase the identification and treatment of life
      threatening injuries is essential and tension pneumothorax is of particular
      importance during this phase. The Advanced Trauma Life Support (ATLS) algorithm
      should be followed for structured treatment. In most cases treatment by insertion
      of a chest tube is sufficient but for some injuries an emergency thoracotomy is
      unavoidable as a life-saving intervention. In the further treatment especially a
      flail chest and retained hemothorax are responsible for complications, such as
      acute lung failure and thoracic empyema. Early operative interventions in the
      sense of rib fracture stabilization and thoracoscopy-assisted evacuation of
      hematomas can help to prevent such complications.

PMID- 29651514
TI  - Perspectives in football medicine.
AB  - The high injury rate among men's professional football players is well-known.
      Therefore, the Union of European Football Associations (UEFA) launched an injury
      study already in 2001. This study, the UEFA Elite Club Injury Study (ECIS),
      currently includes data from a total of 51 clubs from 18 European countries with
      more than 14,000 registered injuries. With the 21st World Cup (WC) in Russia just
      around the corner, we have from our study identified a higher match injury rate
      and a higher proportion of severe injuries in the European Championships compared
      to the preceding club competitive seasons. Moreover, we have also recently showed
      that the muscle injury rate is higher when players are given a recovery window of
      five days or less between two matches. Considering the congested match schedule
      of the upcoming WC, it is therefore likely that injuries and fatigue once again
      will be a topic of discussion this summer.

PMID- 29651515
TI  - [Erratum to: Osteoid osteoma in the scaphoid bone as cause of radiocarpal pain in
      a 15-year-old patient].

PMID- 29651516
TI  - [Skin cancer screening and treatment costs : Utilisation of the skin cancer
      screening and skin cancer treatment costs in organ transplant recipients].
AB  - BACKGROUND: Organ transplant recipients have an up to 250-times higher risk to
      develop skin cancer. This article evaluated the utilisation of skin cancer
      screening and the treatment costs for skin cancer in organ transplant recipients.
      Patients of the health insurance AOK Bremen/Bremerhaven had been identified and
      the need for skin cancer prevention trainings was derived. METHODS: The number of
      organ transplant recipients (ICD code Z94.0-4) with and without any history of
      skin cancer (ICD code C43/C44), the utilisation of dermatologic health care
      services, and the costs for treatments with the diagnosis Z94.0-4 with and
      without C43/C44 were evaluated. The analyses were carried out for the period from
      2009-2014 by using the accounting systems of the AOK. RESULTS: Between 2009 and
      2014, 231 organ transplant recipients had been recorded. By mid-2014, 20% of
      these insured persons developed skin cancer and the mean incidence was 2.76% per
      year. On average, 43% of these patients were seen by a dermatologist at least
      once a year, whereby only 15% of the organ transplant recipients participated in
      the annual skin cancer screening. In 29% of the patients without any history of
      skin cancer, a skin examination was never performed by a dermatologist or a
      general practitioner. In all, 17 inpatient cases of organ transplant recipients
      with the primary diagnosis C43/C44 were analyzed. This resulted in total costs of
      54,707 ? (on average about 3200 ? per case). CONCLUSIONS: The increased incidence
      of skin cancer and the associated treatment costs indicate the need for skin
      cancer prevention training.

PMID- 29651517
TI  - National survey of urogynecological practice patterns among United States OB/GYN
      oral board examinees in different practice settings.
AB  - INTRODUCTION AND HYPOTHESIS: The current urogynecological surgical experience of
      recent OB/GYN graduates in different practice settings is unclear. The aim of
      this study was to evaluate differences in urogynecological surgical care between
      private practitioners (PPs) and other generalist OB/GYN oral board examinees.
      METHODS: A total of 699 OB/GYN oral board examination examinees were administered
      a survey during board preparatory courses with a 70.7% response rate. The primary
      outcome was to determine differences in subjective reported performance of
      urogynecological surgery with and without apical support procedures (female
      pelvic medicine and reconstructive surgery, FPMRS, +/- apical) between PP and
      generalists in other practice models (academic, managed care, other). Secondary
      outcomes included urogynecological case list reporting, referral patterns, and
      residency training. RESULTS: A total of 473 surveys were completed; after
      excluding subspecialists, 210 surveys were completed by PP and 162 by individuals
      in other settings. 6.7% of PPs subjectively reported that they perform FPMRS +
      apical surgery compared with 4.3% of those in other practice settings (p = 0.33).
      Although 29.2% of PPs reported adequate FPMRS training in residency compared with
      39.7% of those in other practice settings (p = 0.04), 53.6% of PPs reported that
      they refer patients with pelvic organ prolapse (POP), compared with 66.5% of
      those in other practice settings (p = 0.013). 38.9% of PPs report that they
      performed POP surgery compared with 27.8% of non-PPs (p = 0.014). CONCLUSIONS:
      Regardless of practice setting, surgical volumes are low and few general OB/GYN
      board examinees report that they perform comprehensive FPMRS +/- apical support
      surgery. The practice environment may affect providers' management of patients
      with pelvic floor disorders.

PMID- 29651518
TI  - Updating impairments and the failure to explore new hypotheses following right
      brain damage.
AB  - We have shown recently that damage to the right hemisphere impairs the ability to
      update mental models when evidence suggests an old model is no longer
      appropriate. We argue that this deficit is generic in the sense that it crosses
      multiple cognitive and perceptual domains. Here, we examined the nature of this
      updating impairment to determine more precisely the underlying mechanisms. We had
      right (RBD, N = 12) and left brain damaged (LBD, N = 10) patients perform
      versions of our picture-morphing task in which pictures gradually morph from one
      object (e.g., shark) to another (e.g., plane). Performance was contrasted against
      two groups of healthy older controls, one matched on age (HCO-age-matched, N = 9)
      and another matched on general level of cognitive ability (HCO-cognitively
      matched, N = 9). We replicated our earlier findings showing that RBD patients
      took longer than LBD patients and HCOs to report seeing the second object in a
      sequence of morphing images. The groups did not differ when exposed to a morphing
      sequence a second time, or when responding to ambiguous images outside the
      morphing context. This indicates that RBD patients have little difficulty
      alternating between known representations or labeling ambiguous images. Instead,
      the difficulty lies in generating alternate hypotheses for ambiguous information.
      Lesion overlay analyses, although speculative given the sample size, are
      consistent with our fMRI work in healthy individuals in implicating the anterior
      insular cortex as critical for updating mental models.

PMID- 29651519
TI  - Root resorption due to orthodontic treatment using self-ligating and conventional
      brackets : A cone-beam computed tomography study.
AB  - OBJECTIVES: Purpose of the present study was to compare external root resorption
      (ERR) volumetrically in maxillary incisors induced by orthodontic treatment using
      self-ligating brackets (Damon Q, DQ) or conventional brackets (Titanium Orthos,
      TO) with the help of cone-beam computed tomography (CBCT). PATIENTS AND METHODS:
      A sample of 32 subjects, with Angle Class I malocclusion and anterior crowding of
      4-10 mm, was divided randomly into two groups: a DQ group, in which self-ligating
      DQ brackets with Damon archwires were used; and a TO group, in which conventional
      TO brackets with large Orthos archwires were applied. The study was conducted
      using CBCT scans taken before (T1), and near the end (9 months after the
      initiation of treatment; T2) of the orthodontic treatment. The extent of ERR was
      determined volumetrically using Mimics software. Changes in root volume were
      evaluated by repeated-measures analysis of variance as well as by paired and
      independent t-tests. RESULTS: While significant differences were found between T1
      and T2 for root volume in both groups (p < 0.05), there was no difference between
      the groups regarding the amount (mm3 or relative change) of ERR (p > 0.05).
      Maxillary central and lateral incisors showed similar volume loss (p > 0.05).
      Furthermore, the TO group showed a higher prevalence of palatinal and proximal
      slanted RR compared with the DQ group (p < 0.05). CONCLUSIONS: It is not possible
      to suggest superiority of one bracket system over the other only considering root
      resorption pattern or amount. Higher incidence of slanted RR found in patients
      treated with the TO system warrants further research to identify possible
      specific causes.

PMID- 29651520
TI  - [Surface modifications of implants. Part 2 : Clinical application].
AB  - The chemical composition, surface structure and topography of a biomaterial have
      an essential influence on the effects of an implant in the human body. In
      orthopedic and trauma surgery they make a relevant contribution to solve the
      current and future challenges. Particularly high are the requirements of
      permanent implants in bone. Besides material aging due to oxidation, implants are
      subjected to cyclic loading that leads to relevant biomechanical wear and
      abrasion. To date significant efforts have been made to minimize adverse implant
      associated immunoreactions as well as the risk of periprosthetic infections. This
      review gives an overview of surface modifications of implants designed for
      clinical application and their effects in vivo. Beside material-specific and
      biological principles, different surface modifications for distinct clinical
      applications are presented. Furthermore, current developmental strategies for the
      targeted clinical application of implant surfaces are outlined.

PMID- 29651521
TI  - [Spondylotic cervical myelopathy : Indication of surgical treatment].
AB  - BACKGROUND: The pathogenesis of cervical spondylotic myelopathy (CSM) is often
      multifactorial. Hence, the treatment of this disease requires a differentiated
      surgical approach in order to adequately address the underlying pathology.
      PURPOSE: The aim of this review is to identify factors that influence the choice
      of treatment strategy and to summarize them in an algorithm that serves as a
      decision aid in choosing the optimal indication for surgical treatment. An
      attempt is made to define the threshold values for the indication of surgical
      treatment and to discuss the ideal timing for performing surgery. MATERIALS AND
      METHODS: On the basis of the published data, the influencing factors on the
      prognosis of CSM, as well as surgical approaches are discussed. RESULTS:
      Circumferential spinal cord compression, a sharply defined myelopathy signal in
      the T2-weighted MRI sequence, and segmental instability at the level of the
      myelopathy signal mean an unfavorable prognosis for the worsening of CSM. The
      most important factors that influence the choice of the surgical access point are
      the sagittal profile of the cervical spine, the extent of myelopathy, the extent
      of stenosis, and the location of the myelopathy-inducing pathology. Previously
      existing neck pain and prior cervical surgery must also be considered.
      DISCUSSION: On the basis of the research carried out, we developed an algorithm
      that could serve as an aid in choosing the right treatment in the setting of
      cervical spondylotic myelopathy.

PMID- 29651522
TI  - Synthesis and application of magnetic molecularly imprinted polymers in sample
      preparation.
AB  - Magnetic molecularly imprinted polymers (MMIPs) have superior advantages in
      sample pretreatment because of their high selectivity for target analytes and the
      fast and easy isolation from samples. To meet the demand of both good magnetic
      property and good extraction performance, MMIPs with various structures, from
      traditional core-shell structures to novel composite structures with a larger
      specific surface area and more accessible binding sites, are fabricated by
      different preparation technologies. Moreover, as the molecularly imprinted
      polymer (MIP) layers determine the affinity, selectivity, and saturated
      adsorption amount of MMIPs, the development and innovation of the MIP layer are
      attracting attention and are reviewed here. Many studies that used MMIPs as
      sorbents in dispersive solid-phase extraction of complex samples, including
      environmental, food, and biofluid samples, are summarized. Graphical abstract The
      application of magnetic molecularly imprinted polymers (MIPs) in the sample
      preparation procedure improves the analytical performances for complex samples.
      MITs molecular imprinting technologies.

PMID- 29651523
TI  - Simple and inexpensive micromachined aluminum microfluidic devices for acoustic
      focusing of particles and cells.
AB  - We introduce a new method to construct microfluidic devices especially useful for
      bulk acoustic wave (BAW)-based manipulation of cells and microparticles. To
      obtain efficient acoustic focusing, BAW devices require materials that have high
      acoustic impedance mismatch relative to the medium in which the
      cells/microparticles are suspended and materials with a high-quality factor. To
      date, silicon and glass have been the materials of choice for BAW-based
      acoustofluidic channel fabrication. Silicon- and glass-based fabrication is
      typically performed in clean room facilities, generates hazardous waste, and can
      take several hours to complete the microfabrication. To address some of the
      drawbacks in fabricating conventional BAW devices, we explored a new approach by
      micromachining microfluidic channels in aluminum substrates. Additionally, we
      demonstrate plasma bonding of poly(dimethylsiloxane) (PDMS) onto micromachined
      aluminum substrates. Our goal was to achieve an approach that is both low cost
      and effective in BAW applications. To this end, we micromachined aluminum 6061
      plates and enclosed the systems with a thin PDMS cover layer. These aluminum/PDMS
      hybrid microfluidic devices use inexpensive materials and are simply constructed
      outside a clean room environment. Moreover, these devices demonstrate
      effectiveness in BAW applications as demonstrated by efficient acoustic focusing
      of polystyrene microspheres, bovine red blood cells, and Jurkat cells and the
      generation of multiple focused streams in flow-through systems. Graphical
      abstract The aluminum acoustofluidic device and the generation of multinode
      focusing of particles.

PMID- 29651524
TI  - Natural deep eutectic solvents as the major mobile phase components in high
      performance liquid chromatography-searching for alternatives to organic solvents.
AB  - Over the past six decades, acetonitrile (ACN) has been the most employed organic
      modifier in reversed-phase high-performance liquid chromatography (RP-HPLC),
      followed by methanol (MeOH). However, from the growing environmental awareness
      that leads to the emergence of "green analytical chemistry," new research has
      emerged that includes finding replacements to problematic ACN because of its low
      sustainability. Deep eutectic solvents (DES) can be produced from an almost
      infinite possible combinations of compounds, while being a "greener" alternative
      to organic solvents in HPLC, especially those prepared from natural compounds
      called natural DES (NADES). In this work, the use of three NADES as the main
      organic component in RP-HPLC, rather than simply an additive, was explored and
      compared to the common organic solvents ACN and MeOH but additionally to the
      greener ethanol for separating two different mixtures of compounds, one
      demonstrating the elution of compounds with increasing hydrophobicity and the
      other comparing molecules of different functionality and molar mass. To utilize
      NADES as an organic modifier and overcome their high viscosity monolithic
      columns, temperatures at 50  degrees C and 5% ethanol in the mobile phase were
      used. NADES are shown to give chromatographic performances in between those
      observed for ACN and MeOH when eluotropic strength, resolution, and peak capacity
      were taken into consideration, while being less environmentally impactful as
      shown by the HPLC-Environmental Assessment Tool (HPLC-EAT) metric. With the
      development of proper technologies, DES could open a new class of mobile phases
      increasing the possibilities of new separation selectivities while reducing the
      environmental impact of HPLC analyses. Graphical abstract Natural deep eutectic
      solvents versus traditional solvents in HPLC.

PMID- 29651525
TI  - Multielement analysis of Zanthoxylum bungeanum Maxim. essential oil using ICP
      MS/MS.
AB  - The concentrations of trace elements (Cr, Ni, As, Cd, Hg, and Pb) in Zanthoxylum
      bungeanum Maxim. essential oil (ZBMEO) were determined by inductively coupled
      plasma tandem mass spectrometry. The ZBMEO sample was directly analyzed after
      simple dilution with n-hexane. Aiming for a relatively high vapor pressure of n
      hexane and its resultant loading on plasma, we used a narrow injector torch and
      optimized plasma radio frequency power and carrier gas flow to ensure stable
      operation of the plasma. An optional gas flow of 20% O2 in Ar was added to the
      carrier gas to prevent the incomplete combustion of highly concentrated organic
      carbon in plasma and the deposition of carbon on the sampling and skimmer cone
      orifices. In tandem mass spectrometry mode, O2 was added to the
      collision/reaction cell to eliminate the interferences. The limits of detection
      for Cr, Ni, As, Cd, Hg, and Pb were 2.26, 1.64, 2.02, 1.35, 1.76, and 0.97 ng L
      1, respectively. After determination of 23 ZBMEO samples from different regions
      in China, we found that the average concentration ranges of trace elements in the
      23 ZBMEO samples were 0.72-6.02 ng g-1, 0.09-2.87 ng g-1, 0.21-5.84 ng g-1, 0.16
      2.15 ng g-1, 0.13-0.92 ng g-1, and 0.17-0.73 ng g-1 for Cr, Ni, As, Cd, Hg, and
      Pb, respectively. The trace elements in ZBMEO differed significantly when
      different extraction technologies were used. The study revealed that the contents
      of the toxic elements As, Cd, Hg, and Pb were extremely low, and hence they are
      unlikely to pose a health risk following ZBMEO ingestion. Graphical abstract The
      working mechanism of sample analysis by ICP-MS/MS.

PMID- 29651526
TI  - Surface plasmon resonance sensing: from purified biomolecules to intact cells.
AB  - Surface plasmon resonance (SPR) has become a well-recognized label-free technique
      for measuring the binding kinetics between biomolecules since the invention of
      the first SPR-based immunosensor in 1980s. The most popular and traditional
      format for SPR analysis is to monitor the real-time optical signals when a
      solution containing ligand molecules is flowing over a sensor substrate
      functionalized with purified receptor molecules. In recent years, rapid
      development of several kinds of SPR imaging techniques have allowed for mapping
      the dynamic distribution of local mass density within single living cells with
      high spatial and temporal resolutions and reliable sensitivity. Such capability
      immediately enabled one to investigate the interaction between important
      biomolecules and intact cells in a label-free, quantitative, and single cell
      manner, leading to an exciting new trend of cell-based SPR bioanalysis. In this
      Trend Article, we first describe the principle and technical features of two
      types of SPR imaging techniques based on prism and objective, respectively. Then
      we survey the intact cell-based applications in both fundamental cell biology and
      drug discovery. We conclude the article with comments and perspectives on the
      future developments. Graphical abstract Recent developments in surface plasmon
      resonance (SPR) imaging techniques allow for label-free mapping the mass
      distribution within single living cells, leading to great expansions in
      biomolecular interactions studies from homogeneous substrates functionalized with
      purified biomolecules to heterogeneous substrates containing individual living
      cells.

PMID- 29651527
TI  - Simultaneous determination of amantadine and rimantadine in feed by liquid
      chromatography-Qtrap mass spectrometry with information-dependent acquisition.
AB  - A sensitive method for simultaneous determination of amantadine and rimantadine
      in feed was developed using an ultra-high-performance liquid chromatography
      triple quadrupole linear ion trap mass spectrometry (UHPLC-Qtrap-MS) in the
      multiple reaction monitoring information-dependent acquisition-enhanced product
      ion (MRM-IDA-EPI) mode, and employing the mixed cation exchange (MCX) solid-phase
      extraction column as sample cleanup and amantadine-d15 and rimantadine-d4 as
      internal standards, respectively. Compared to traditional MRM mode, for the
      targeted drugs in feed simultaneously both the secondary mass spectra and MRM
      information can be obtained using UHPLC-Qtrap-MS with MRM-IDA-EPI mode, and thus
      more accurate qualitative confirmation results achieved even at lower
      concentration of 0.2 MUg/L in acceptable purity fit values. After optimization of
      sample preparation, good linearities (R > 0.9994) were obtained over the
      concentration range from 1 to 200 MUg/L for amantadine and rimantadine. The
      precision was validated by intra-day and inter-day, and the relative standard
      deviations were all within 9.61%. Mean recoveries ranged from 76.1 to 112% at
      spiked concentrations of 0.5-100 MUg/kg in three types of feed samples, including
      formula feed and complex concentrated feed for pigs and premix feed for chicken.
      The limits of detection (LODs) and quantification (LOQs) were 0.2 and 0.5 MUg/kg
      for both drugs, respectively. The application in real feed samples further proved
      the accuracy and reliability of the developed method. This method provides an
      important tool to detect illegal uses of amantadine and rimantadine in feed.
      Graphical abstract Simultaneous quantitation and qualitative confirmation of
      amantadine and rimantadine in feed by MRM-IDA-EPI.

PMID- 29651528
TI  - Ternary mixed-mode silica sorbent of solid-phase extraction for determination of
      basic, neutral and acidic drugs in human serum.
AB  - In this study, a ternary mixed-mode silica sorbent (TMSS) with octamethylene,
      carboxyl, and amino groups was prepared via Cu(I)-catalyzed azide-alkyne
      cycloaddition (CuAAC) click reaction and a subsequent reduction of azide to
      primary amine. While used in solid-phase extraction (SPE), the retention behavior
      of TMSS towards a total of nine kinds of basic, neutral, and acidic drugs was
      investigated in detail. The results revealed that hydrophobic, ion-exchange
      interaction, and electrostatic repulsion between TMSS and the analytes were
      closely related to the retention behavior of TMSS. Besides, the log Kow value of
      the analyte was also a factor influencing the retention behavior of analytes on
      TMSS. The nine analytes could be retained by TMSS simultaneously and then, were
      eluted into two fractions according to the acid-base property of the analytes for
      further determinations. The acidic and neutral analytes were in one fraction, and
      the basic ones in the other fraction. When used to treat the human serum spiked
      with the nine drugs, TMSS offered higher recoveries than BakerBond CBA and
      comparable recoveries to Oasis WCX. It should be noted TMSS had better purifying
      capability for human serum than Oasis WCX. Under the optimized SPE conditions, a
      method of SPE hyphenated to high-performance liquid chromatography-ultraviolet
      detection (HPLC-UV) for determination of the basic, neutral, and acidic drugs
      spiked in human serum was established. For the nine drugs, the linear ranges were
      all between 5.0 and 1000 MUg L-1 with correlation coefficients (R2) above 0.9990,
      and the limits of detection (LODs) were in the range of 0.8-2.3 MUg L-1. The
      intra-day and inter-day relative standard deviations (RSDs) were less than 5.3
      and 8.8%, respectively. Graphical abstract Treating drugs in human serum by SPE
      with ternary mixed-mode silica sorbent.

PMID- 29651529
TI  - Application of problem-based learning in instrumental analysis teaching at
      Northeast Agricultural University.

PMID- 29651530
TI  - The requirements for low-temperature plasma ionization support miniaturization of
      the ion source.
AB  - Ambient ionization mass spectrometry (AI-MS), the ionization of samples under
      ambient conditions, enables fast and simple analysis of samples without or with
      little sample preparation. Due to their simple construction and low resource
      consumption, plasma-based ionization methods in particular are considered ideal
      for use in mobile analytical devices. However, systematic investigations that
      have attempted to identify the optimal configuration of a plasma source to
      achieve the sensitive detection of target molecules are still rare. We therefore
      used a low-temperature plasma ionization (LTPI) source based on dielectric
      barrier discharge with helium employed as the process gas to identify the factors
      that most strongly influence the signal intensity in the mass spectrometry of
      species formed by plasma ionization. In this study, we investigated several
      construction-related parameters of the plasma source and found that a low wall
      thickness of the dielectric, a small outlet spacing, and a short distance between
      the plasma source and the MS inlet are needed to achieve optimal signal intensity
      with a process-gas flow rate of as little as 10 mL/min. In conclusion, this type
      of ion source is especially well suited for downscaling, which is usually
      required in mobile devices. Our results provide valuable insights into the LTPI
      mechanism; they reveal the potential to further improve its implementation and
      standardization for mobile mass spectrometry as well as our understanding of the
      requirements and selectivity of this technique. Graphical abstract Optimized
      parameters of a dielectric barrier discharge plasma for ionization in mass
      spectrometry. The electrode size, shape, and arrangement, the thickness of the
      dielectric, and distances between the plasma source, sample, and MS inlet are
      marked in red. The process gas (helium) flow is shown in black.

PMID- 29651532
TI  - 32nd Annual Meeting of the European Society for Hyperthermic Oncology.

PMID- 29651531
TI  - Effects of glaucocalyxin A on human liver cancer cells as revealed by GC/MS- and
      LC/MS-based metabolic profiling.
AB  - Studies have documented the potential antitumor activities of glaucocalyxin A
      (GLA), an ent-kaurene diterpenoid isolated from Rabdosia japonica. However, the
      metabolic mechanism underlying the antitumor activity of GLA remains largely
      unknown. The effects of GLA on the metabolome of human liver cancer cells using
      GC/MS- and LC/MS-based metabolic profiling have been investigated. An untargeted
      metabolomics approach in conjunction with orthogonal projection to latent
      structures-discriminant analysis (OPLS-DA) has been developed to characterize the
      metabolic modifications induced by GLA treatment in human hepatoma cell line
      SMMC7721. Results demonstrated that cells cultured in the presence or absence of
      GLA displayed different metabolic profiles: the treatment induced an increased
      purine metabolism, pyrimidine metabolism, and sphingolipid metabolism and a
      decreased amino acid metabolism. At the same time, GLA treatment induced cell
      apoptosis and cell cycle arrested at G2/M phase in a dose-dependent manner. In
      addition, two representative apoptosis-inducing cytotoxic agents were selected as
      positive control drugs to validate the reasonableness and accuracy of our
      metabolomic investigation on GLA. The study displayed a systemic metabolic
      alteration induced by GLA treatment, showing the impaired physiological activity
      of SMMC7721 cells, which also indicated anti-proliferative and apoptotic effects
      of GLA. In the meantime, GC/MS- and LC/MS-based metabolomics applied to cell
      culture enhanced our current understanding of the metabolic response to GLA
      treatment and its mechanism; such an approach could be transferred to study the
      mechanism of other anticancer drugs. Graphical abstract A systemic metabolic
      alteration induced by glaucocalyxin A (GLA) treatment of SMMC-7721 cells.

PMID- 29651533
TI  - Spatial orientation of coronary arteries and its implication for breast and
      thoracic radiotherapy-proposing "coronary strip" as a new organ at risk.
AB  - OBJECTIVES: Radiotherapy for breast cancer has been associated with various side
      effects including cardiac sequelae. Our study aimed to define the spatial arc of
      spread of coronary vessels in a radian angle. MATERIALS AND METHODS: We analysed
      the records of 51 CT coronary angiographies done in our hospital from January
      2016 to July 2016. Left anterior descending (LAD) and right coronary (RC) were
      contoured for each patient. In each axial section, the radial spread of each
      artery was noted. A 5 mm brush tool was used to join the start and stop angles
      for making the summated "coronary strips". RESULTS: Start and end angle of LAD
      with 95% confidence interval (CI) (in clockwise direction) were 23.9 +/- 4
      degrees  and 79.0 +/- 6.6 degrees , respectively. Mean LAD arc length +/- SD
      (standard deviation) noted was 55.1 degrees  +/- 7.7 degrees  (95% CI). For RC
      the smallest start angle and the largest end angle in all patients was 297.6
      degrees  and 322.6 degrees , respectively. RC start angle, end angle and arc
      length for 95% confidence interval were 322.2 +/- 6.1 degrees , 292.4 +/- 11.6
      degrees  and 29.8 +/- 13.1 degrees , respectively. CONCLUSIONS: Our study
      provides a measure of the radial spread of the coronary arteries, especially from
      the perspective of breast radiotherapy. We have proposed a new organ at risk
      (OAR) of coronary strip. This should provide an easy and cost-effective way to
      delineate the coronary vasculature in breast cancer patients undergoing
      radiotherapy.

PMID- 29651534
TI  - The unimanual handle-to-hand correspondence effect: evidence for a location
      coding account.
AB  - The handle-to-hand correspondence effect refers to faster and more accurate
      responses when the responding hand is aligned with the graspable part of an
      object tool, compared to when they lay on opposite sides. We performed four
      behavioral experiments to investigate whether this effect depends on the
      activation of grasping affordances (affordance activation account) or is to be
      traced back to a Simon effect, resulting from the spatial coding of stimuli and
      responses and from their dimensional overlap (location coding account). We
      manipulated the availability of a response alternative by requiring participants
      to perform either a unimanual go/no-go task (absence of a response alternative)
      or a joint go/no-go task (available response alternative) and the type of
      response required (button-press or grasping response). We found no handle-to-hand
      correspondence effect in the individual go/no-go task either when a button-press
      (Experiment 1A) or a grasping (Experiment 2A) response was required, whereas a
      significant effect emerged in the joint go/no-go task, irrespective of response
      modality (Experiments1B and 2B). These results do not support the idea that
      complex motor affordances are activated for meaningful objects, but are rather
      consistent with the more parsimonious location coding account.

PMID- 29651535
TI  - Cell cycle of the enamel knot during tooth morphogenesis.
AB  - Enamel knot (EK) is known to be a central organ in tooth development, especially
      for cusp patterning. To trace the exact position and movement among the inner
      dental epithelium (IDE) and EK cells, and to monitor the relationship between the
      EK and cusp patterning, it is essential that we understand the cell cycle status
      of the EK in early stages of tooth development. In this study, thymidine
      analogous (IdU, BrdU) staining was used to evaluate the cell cycle phase of the
      primary EK at the early casp stage (E13.0) and the gerbil embryo (E19) in a
      developing mouse embryo. The centerpiece of this study was to describe the cell
      cycle phasing and sequencing during proliferation in the IDE according to the
      expression of IdU and BrdU following their injection at calculated time points.
      The interval time between IdU injection and BrdU injection was set at 4 h. As a
      result, the cell cycle in the IDE of the mouse and gerbil was found to be
      synchronous. Conversely, the cell cycle in primary EKs of mice was much longer
      than that of the IDE. Therefore, the difference of cell cycle of the IDE and the
      EK is related to the diversity of cusp patterning and would provide a new insight
      into tooth morphogenesis.

PMID- 29651536
TI  - Septin localization and function during autophagy.
AB  - Autophagy is a vital conserved recycling process where eukaryotic cells remove
      unwanted proteins and organelles via lysosomal degradation and in turn, generate
      nutrients for the cells. The special feature of autophagy process is the
      formation of double-membrane vesicles called autophagosomes that engulf cellular
      cargo and deliver them to the vacuole or lysosomes for degradation. Inspite of
      more than 40 AuTophaGy (ATG) proteins and several organelles as known membrane
      source, autophagosome biogenesis is not entirely understood. We recently have
      discovered that septins contribute to autophagosome biogenesis. Septins are GTP
      binding proteins, usually localized at the bud neck region and are involved in
      cytokinesis. Here, we show that during autophagy prevalent conditions, septins
      traffic between different cellular compartments such as Golgi, mitochondria,
      endosomes, plasma membrane, and vacuolar membranes.

PMID- 29651537
TI  - Pierre Robin syndrome with caudal regression syndrome-a rare combination of
      congenital syndromes.

PMID- 29651538
TI  - Visualization of the periventricular Virchow-Robin spaces with ependymal
      openings.
AB  - PURPOSE: The morphological relationships between the periventricular Virchow
      Robin spaces (VRSs) and cerebral ventricles have been poorly documented. The
      present study aimed to explore the issue using magnetic resonance imaging.
      METHODS: A total of 211 patients were included in this study. T2-weighted and
      constructive interference in steady state (CISS) sequences were performed in thin
      sliced, coronal sections. RESULTS: On T2-weighted sequence, the periventricular
      VRSs with ependymal openings were identified in 34% of 139 subjects. All the
      openings were located in the lateral wall of the anterior horn. In CISS
      sequences, such VRSs were found in 39% of 72 subjects. The mean age was
      significantly higher in the population with such VRSs compared to those without
      VRSs (p = 0.0047). Of the 58 periventricular VRSs with ependymal openings
      identified on T2-weighted images, 16% were located in the upper, 36% in the
      middle, and 48% in the lower part of the lateral wall. Of the 38 such VRSs
      identified on CISS images, 32% were located in the upper, 24% in the middle, and
      42% in the lower part of the lateral wall, and 3% in the upper part of the medial
      wall. CONCLUSIONS: The ependymal openings of the periventricular VRSs may be
      centered in the lateral wall of the anterior horn. The coronal CISS sequence can
      sensitively delineate the VRSs with ependymal openings.

PMID- 29651539
TI  - Skeletal muscle stem cell characteristics and myonuclei content in patients with
      rheumatoid arthritis: a cross-sectional study.
AB  - To investigate satellite cells (SCs) and myonuclei characteristics in patients
      with rheumatoid arthritis (RA). Resting biopsies from m. vastus lateralis were
      obtained from thirteen RA patients and thirteen matched healthy controls (CON).
      Muscle biopsies were immunohistochemically stained and analyzed for fiber type
      specific content of SCs (Pax7+), proliferating SCs (Pax7+/MyoD+) and
      differentiating SCs (myogenin+). Furthermore, we quantified fiber type specific
      content of myonuclei and myofiber cross-sectional area (CSA). Finally, newly
      formed/regenerating fibers expressing neonatal MHC (nMHC+) were determined. The
      fiber type specific number of SCs did not differ between RA patients and CON, nor
      did the content of proliferating or differentiating SCs. In contrast, the content
      of myonuclei per fiber was higher in RA patients than CON for both type I (2.01
      +/- 0.41 vs. 1.42 +/- 0.40 myonuclei/fiber, p < 0.01) and type II fibers (2.01 +/
      0.41 vs. 1.37 +/- 0.32 myonuclei/fiber, p < 0.01). No differences were observed
      in fiber composition, fiber type specific CSA or content of nMHC+ fibers. Our
      results indicate an increased propensity for myogenic differentiation of SC
      leading to an elevated myonuclear content in the skeletal muscle of RA patients.
      It is hypothesized that this could be a compensatory regulatory response related
      to the chronic inflammation in these patients.

PMID- 29651540
TI  - Identifying Non-invasive Tools to Distinguish Acute Myocarditis from Dilated
      Cardiomyopathy in Children.
AB  - There is often a diagnostic dilemma in pediatric patients presenting with
      depressed ventricular function, as myocarditis and dilated cardiomyopathy (DCM)
      of other etiologies can appear very similar. Accurate identification is critical
      to guide treatment and to provide families with the most accurate expectation of
      long-term outcomes. The objective of this study was to identify patterns of
      clinical presentation and to assess non-invasive measures to differentiate
      patients with acute myocarditis from other forms of DCM. We identified all
      children (< 18 years) from our institution with a diagnosis of idiopathic DCM or
      myocarditis based on endomyocardial biopsy or explant pathology (1996-2015).
      Characteristics at the time of presentation were compared between patients with a
      definite diagnosis of myocarditis and those with idiopathic DCM. Data collected
      included clinical and laboratory data, radiography, echocardiography, and cardiac
      catheterization data. A total of 58 patients were included in the study; 46 (79%)
      with idiopathic DCM and 12 (21%) with acute myocarditis. Findings favoring a
      diagnosis of myocarditis included a history of fever (58 vs. 15%, p = 0.002),
      arrhythmia (17 vs. 0%, p = 0.003), higher degree of cardiac enzyme elevation,
      absence of left ventricular dilation (42 vs. 7%, p = 0.002), segmental wall
      motion abnormalities (58 vs. 13%, p = 0.001), lower left ventricular dimension z
      score (3.7 vs. 5.2, p = 0.031), and less severe depression of left ventricular
      systolic function. There are notable differences between patients with
      myocarditis and other forms of DCM that can be detected non-invasively at the
      time of presentation without the need for endomyocardial biopsy. These data
      suggest that it may be possible to develop a predictive model to differentiate
      myocarditis from other forms of DCM using non-invasive measures.

PMID- 29651541
TI  - Monovalerin and trivalerin increase brain acetic acid, decrease liver succinic
      acid, and alter gut microbiota in rats fed high-fat diets.
AB  - PURPOSE: Short-chain fatty acids (SCFA) are known for their anti-inflammatory
      properties and may also prevent against the development of metabolic diseases.
      This study investigated possible effects of two valeric acid esters, monovalerin
      (MV) and trivalerin (TV) in rats fed high-fat diets. METHODS: Four groups of rats
      were given a low-fat diet (LF) or a high-fat control diet (HFC) with or without
      supplementation of MV or TV (5 g/kg) for 3 weeks (n = 7/group). SCFA (caecum,
      blood, liver and brain), succinic acid (liver), microbiota (caecum), lipid
      profile (liver and blood) and the inflammatory biomarker, lipopolysaccharide
      binding protein (blood) were analysed at the end of the experiment. RESULTS:
      Supplementation of MV and TV to a high-fat diet increased 1.5-fold the amounts of
      acetic acid in the brain and 1.7-fold serum concentration of valeric acid,
      whereas liver succinic acid was reduced by 1.5-fold. Although liver triglyceride
      levels were higher in both MV and TV groups compared with the LF group, liver
      LDL/HDL ratio was lower in the MV group (P < 0.05). The caecal microbiota
      composition was altered, with threefold higher abundance of Bacteroidetes and
      higher ratio of Bacteroidetes/Firmicutes in the MV group compared with the HFC
      and LF groups. Acetic acid in the brain was negatively correlated with TM7,
      family S24-7 and rc4-4, and positively associated to Tenericutes and
      Anaeroplasma. CONCLUSIONS: The present study shows that MV and TV in the
      specified dose can affect caecal microbiota composition and, therefore, bacterial
      metabolites in the liver, serum and brain as well as the lipid profile in the
      liver.

PMID- 29651542
TI  - The lymphocyte-to-monocyte ratio as a prognostic indicator in head and neck
      cancer: a systematic review and meta-analysis.
AB  - PURPOSE: The aim of this systematic review and meta-analysis was to investigate
      the relationship between the pre-treatment lymphocyte-to-monocyte ratio (LMR) and
      prognosis in HNC. METHODS: PubMed (via the Web), Embase, Scopus, and the Cochrane
      Library were searched. A systematic review and meta-analysis was done to generate
      the pooled hazard ratios (HR) for overall survival (OS) and disease-free survival
      (DFS). RESULTS: Our analysis included the results of 4260 patients in seven
      cohorts. The pooled data demonstrated that an elevated LMR was associated with
      significantly improved OS (HR 0.5; 95% CI 0.44-0.57), and DFS (HR 0.70; 95% CI
      0.62-0.80). Of note, there was no detectable heterogeneity in either OS (I2 = 0%)
      or DFS (I2 = 0%). CONCLUSIONS: An elevated LMR may be an indicator of favorable
      prognosis in HNC. However, our results should be interpreted with some degree of
      caution due to the retrospective nature of cohort studies. Further research with
      high-quality prospective studies is needed to confirm the effect of LMR in HNC
      prognosis.

PMID- 29651543
TI  - SNP-based next-generation sequencing reveals low-level mixed chimerism after
      allogeneic hematopoietic stem cell transplantation.

PMID- 29651544
TI  - The Effects of Sediment Classification Pattern on a Water Column Organism,
      Ceriodaphnia dubia.
AB  - The sediment compartment stands out because it functions as both a temporary sink
      of pollutants and a potential source of these elements that may become available
      to the water column.This study aimed to correlate the concentrations of total
      metals in the crude sediment and in the interstitial water with the ecotoxicity
      in the water column using an a modified sediment ecotoxicity test with
      Ceriodaphnia dubia. The results indicate that the sediment may contribute to the
      toxicity in the water column and that such toxicity is possibly not related to
      the metals present. Based on the chemical analysis of the metals, the Canadian
      Sediment Quality Guidelines (SQGs) would frame the sediment as non-toxic to
      benthic organisms, but the SQGs have no reference standards for possible effects
      on nektonic organisms. Due to the complexity of this compartment, it is
      fundamental to evaluate the interactions of the different pollutants in the
      system and possible effects on the nektonic organisms.

PMID- 29651545
TI  - Extracardiac 18F-florbetapir imaging in patients with systemic amyloidosis: more
      than hearts and minds.
AB  - PURPOSE: 18F-Florbetapir has been reported to show cardiac uptake in patients
      with systemic light-chain amyloidosis (AL). This study systematically assessed
      uptake of 18F-florbetapir in patients with proven systemic amyloidosis at sites
      outside the heart. METHODS: Seventeen patients with proven cardiac amyloidosis
      underwent 18F-florbetapir PET/CT imaging, 15 with AL and 2 with transthyretin
      amyloidosis (ATTR). Three patients had repeat scans. All patients had
      protocolized assessment at the UK National Amyloidosis Centre including imaging
      with 123I-serum amyloid P component (SAP). 18F-Florbetapir images were assessed
      for areas of increased tracer accumulation and time-uptake curves in terms of
      standardized uptake values (SUVmean) were produced. RESULTS: All 17 patients
      showed 18F-florbetapir uptake at one or more extracardiac sites. Uptake was seen
      in the spleen in 6 patients (35%; 6 of 9, 67%, with splenic involvement on 123I
      SAP scintigraphy), in the fat in 11 (65%), in the tongue in 8 (47%), in the
      parotids in 8 (47%), in the masticatory muscles in 7 (41%), in the lungs in 3
      (18%), and in the kidney in 2 (12%) on the late half-body images. The 18F
      florbetapir spleen retention index (SRI) was calculated. SRI >0.045 had 100%
      sensitivity/sensitivity (in relation to 123I-SAP splenic uptake, the current
      standard) in detecting splenic amyloid on dynamic imaging and a sensitivity of
      66.7% and a specificity of 100% on the late half-body images. Intense lung uptake
      was seen in three patients, one of whom had lung interstitial infiltration
      suggestive of amyloid deposition on previous high-resolution CT. Repeat imaging
      showed a stable appearance in all three patients suggesting no early impact of
      treatment response. CONCLUSION: 18F-Florbetapir PET/CT is a promising tool for
      the detection of extracardiac sites of amyloid deposition. The combination of
      uptake in the heart and uptake in the spleen on 18F-florbetapir PET/CT, a
      hallmark of AL, suggests that this tracer holds promise as a screening tool for
      AL.

PMID- 29651546
TI  - Is there an optimal method for measuring baseline metabolic tumor volume in
      diffuse large B cell lymphoma?

PMID- 29651547
TI  - [Prevalence of wearing glasses for children and adolescents in Germany and their
      ophthalmological care : Results of the nationwide KiGGS baseline survey (2003
      2006)].
AB  - BACKGROUND: Vision-relevant refractive errors in children require regular
      ophthalmological control examinations. In this study we estimated the prevalence
      of wearing glasses for children and adolescents in Germany and the frequency of
      ophthalmological care. METHODS: We analyzed data of the German Health Interview
      and Examination Survey for Children and Adolescents (KiGGS, baseline survey 2003
      2006, N = 17,640). Wearing glasses was documented from the age of 3 years in the
      examination part. We estimated the prevalence of wearing glasses and investigated
      the relationship with ophthalmological care during the preceding 12 months.
      Multivariable logistic regression analysis was used to calculate adjusted odds
      ratios (OR) and 95% confidence intervals (95%CI). Associations were adjusted for
      age, gender, socioeconomic status, migration background, residence (East/West
      Germany), participation in regular pediatric check-ups, and presence of
      strabismus. RESULTS: The prevalence of wearing glasses was 19.7% (95% CI: 18.8
      20.5%) in the age range of 3-17 years. The prevalence was higher in girls (22.1%;
      21.0-23.3%) compared to boys (17.3%; 16.3-18.3%) and increased with age up to
      29.2% (27.6-30.9%) in the age group 14-17 years. The frequency of
      ophthalmological care within the last 12 months was 61.6% (59.4-63.8%) for those
      wearing glasses and 15.2% (14.3-6.2%) for those without glasses. Regression
      analysis revealed an association between ophthalmological care and wearing
      glasses (OR = 11.4; 10.1-13.0). CONCLUSION: In Germany, wearing glasses depends
      on gender and age and almost one third of adolescents already wear glasses. The
      majority of children and adolescents wearing glasses visit an ophthalmologist
      once a year.

PMID- 29651548
TI  - [Diagnosis of dry eye disease].
AB  - Dry eye disease (DED) is one of the most common ophthalmological diseases with an
      increasing prevalence in recent years. Numerous general and ocular risk factors
      exist for the development of DED. The pathogenesis of DED is multifactorial and
      complex, characterized by a loss of homeostasis of the tear film, inflammatory
      mechanisms at the ocular surface, hyperosmolarity of tears and neurosensory
      abnormalities. DED is classified into the two sub-categories, aqueous deficient
      dry eye and evaporative dry eye. Apart from a detailed patient history, basic and
      complementary diagnostic tests are necessary to enable an individualized and
      efficient therapy. Moreover, subjective symptom questionnaires and
      interdisciplinary cooperations are beneficial in a thorough work-up of these
      patients.

PMID- 29651549
TI  - [No increase in myopia?]

PMID- 29651550
TI  - [Prevalence of spectacle wearers in Germany : Clear increase from 1952-2014].

PMID- 29651551
TI  - Antimicrobial Ingredients as Preservative Booster and Components of Self
      Preserving Cosmetic Products.
AB  - This review reports cosmetic ingredients with antimicrobial activity including
      synthetic and natural (plant and microbial) origin as alternative for
      preservatives used in cosmetics as well described mechanism of their action.

PMID- 29651552
TI  - Prevention of High-Level Daptomycin-Resistance Emergence In Vitro in
      Streptococcus mitis-oralis by Using Combination Antimicrobial Strategies.
AB  - Among the viridans group streptococci, S. mitis-oralis strains are frequently
      resistant to multiple beta-lactams and tolerant to vancomycin (VAN). This
      scenario has led to the proposed clinical use of newer agents, like daptomycin
      (DAP) for such S. mitis-oralis strains. However, recent recognition of the rapid
      and durable emergence of high-level DAP-resistance (DAP-R; DAP MICs > 256 ug/ml)
      induced by DAP exposures in vitro and in vivo has dampened enthusiasm for such
      approaches. In this study, we evaluated a broad range of DAP combination regimens
      in vitro for their capacity to prevent emergence of high-level DAP-R in a
      prototype S. mitis-oralis strain (351) during serial passage experiments,
      including DAP + either gentamicin (GEN), rifampin (RIF), trimethoprim
      sulfamethoxazole (TMP-SMX), imipenem (IMP), ceftaroline (CPT), tedizolid (TDZ),
      or linezolid (LDZ). In addition, we assessed selected DAP combination regimens
      for their ability to exert either an early bactericidal impact and/or
      synergistically kill the S. mitis-oralis study strain. During serial passage,
      three of the eight antibiotic combinations (DAP + GEN, CPT, or TMP- SMX)
      exhibited significantly reduced DAP MICs (~ by 8-40 fold) vs serial exposure in
      DAP alone (DAP MICs > 256 ug/ml). In addition, combinations of DAP + GEN and DAP
      + CPT were both bactericidal and synergistic in early time-kill curve
      interactions.

PMID- 29651553
TI  - Fistulectomy with primary sphincter reconstruction.
AB  - AIM: Despite modern medical techniques, anatomically proximal (high) anal
      fistulas are still a challenge in colorectal surgery. In previous years, the
      standard of care was complete fistulectomy with a high rate of continence
      disorders. Over the past 20 to 30 years, sphincter-saving procedures have gained
      wide acceptance. They represent the technique used in these cases. Additionally,
      many patients received indefinite treatment, namely the placement of a seton to
      maintain surgical drainage. The main problem with all fistula surgical
      possibilities is the high recurrence rate of 30 to 50% in flap procedures and
      100% persistence in seton treatments. In recent years, a direct repair (primary
      reconstruction) in distal fistulas was instigated and shows excellent results. It
      allowed our technique for proximal (high) anal fistulas to evolve. METHOD: All
      patients who underwent surgery at the University Medical Center Mannheim,
      Department of Colo-proctology (from 06/2003 to 11/2015), were retrospectively
      evaluated using a prospective database. Patients who underwent fistulectomy with
      primary sphincter reconstruction were all included. RESULTS: The primary healing
      rate, after a mean follow-up of 11 months (7 to 200 months), was 88.2% (374 of
      424). Taking into account revisionary surgeries with secondary sphincter repair,
      this rate reaches 95.8% (406 of 424). Factors such as gender and fistula location
      as related to the sphincter had significant influence on the study outcome,
      whereas variables such as the amount of reconstructed muscle (in mm), number of
      revisions, patient age, other anal operations, and concomitant medication did
      not. The incontinence of a subgroup of 148 patients was evaluated in detail by
      way of a questionnaire. Even at a preoperative baseline, 9.6% of those patients
      reported some minor degree of continence disorders. After the procedure,
      incontinence disorders were observed in 34 patients (23.0%), with 23 of these
      patients suffering from flatus incontinence (15.5%), 10 patients from liquid
      incontinence (6.8%), and 1 patient from solid fecal incontinence. CONCLUSION:
      Fistulectomy with primary sphincter reconstruction is a feasible procedure
      resulting in a low recurrence rate. No other procedure has shown better results
      in transsphincteric fistulas. Continence disorders seem to be of minor
      relevance/consequence for these patients.

PMID- 29651554
TI  - Dual-species biofilm of Listeria monocytogenes and Escherichia coli on stainless
      steel surface.
AB  - Listeria monocytogenes is a Gram-positive bacterium commonly associated with
      foodborne diseases. Due its ability to survive under adverse environmental
      conditions and to form biofilm, this bacterium is a major concern for the food
      industry, since it can compromise sanitation procedures and increase the risk of
      post-processing contamination. Little is known about the interaction between L.
      monocytogenes and Gram-negative bacteria on biofilm formation. Thus, in order to
      evaluate this interaction, Escherichia coli and L. monocytogenes were tested for
      their ability to form biofilms together or in monoculture. We also aimed to
      evaluate the ability of L. monocytogenes 1/2a and its isogenic mutant strain
      (DeltaprfA DeltasigB) to form biofilm in the presence of E. coli. We assessed the
      importance of the virulence regulators, PrfA and sigmaB, in this process since
      they are involved in many aspects of L. monocytogenes pathogenicity. Biofilm
      formation was assessed using stainless steel AISI 304 #4 slides immersed into
      brain heart infusion broth, reconstituted powder milk and E. coli preconditioned
      medium at 25  degrees C. Our results indicated that a higher amount of biofilm
      was formed by the wild type strain of L. monocytogenes than by its isogenic
      mutant, indicating that prfA and sigB are important for biofilm development,
      especially maturation under our experimental conditions. The presence of E. coli
      or its metabolites in preconditioned medium did not influence biofilm formation
      by L. monocytogenes. Our results confirm the possibility of concomitant biofilm
      formation by L. monocytogenes and E. coli, two bacteria of major significance in
      the food industry.

PMID- 29651555
TI  - Larval neurogenesis in the copepod Tigriopus californicus (Tetraconata,
      Multicrustacea).
AB  - Arthropod early neurogenesis shows distinct patterns that have been interpreted
      in an evolutionary framework. For instance, crustaceans and Hexapoda form the
      taxon Tetraconata and share the differentiation of specific neural precursors,
      the neuroblasts, a character which sets them apart from Chelicerata and
      Myriapoda. Neuroblasts are relatively large stem cells that generate ganglion
      mother cells by asymmetric divisions. Ganglion mother cells typically divide once
      to give rise to neurons and glia cells. In hexapods, neuroblasts segregate from
      the neuroectoderm before they begin their characteristic proliferative activity.
      In the crustaceans studied so far, neuroblasts remain in the neuroectoderm. Yet,
      detailed studies on early neurogenesis of crustaceans at the cellular level are
      largely restricted to some malacostracan and branchiopod species. Crustaceans are
      very diverse and likely paraphyletic with respect to hexapods. Hence, knowledge
      about neural differentiation in other crustacean taxa might contribute to the
      understanding of evolution of neurogenesis in Tetraconata. Here, we describe the
      early neurogenesis during naupliar development of the copepod Tigriopus
      californicus. We show that neuroblasts are present that generate ganglion mother
      cells, which in turn divide to give rise to neurons of the ventral nerve cord.
      These two neural precursor cell types and their specific arrangement correspond
      to what has been found in other crustaceans. One obvious difference concerns the
      relative size of the neuroblasts, which are not much larger than their progeny.
      Our results complement the picture of neural differentiation in crustaceans and
      suggest that superficially located neuroblasts are likely the ancestral condition
      in Tetraconata.

PMID- 29651556
TI  - Neurospheres from neural stem/neural progenitor cells (NSPCs) of non
      hydrocephalic HTx rats produce neurons, astrocytes and multiciliated ependyma:
      the cerebrospinal fluid of normal and hydrocephalic rats supports such a
      differentiation.
AB  - Fetal onset hydrocephalus and abnormal neurogenesis are two inseparable phenomena
      turned on by a cell junction pathology first affecting neural stem/progenitor
      cells (NSPCs) and later the multiciliated ependyma. The neurological impairment
      of children born with hydrocephalus is not reverted by derivative surgery. NSPCs
      and neurosphere (NE) grafting into the cerebrospinal fluid (CSF) of hydrocephalic
      fetuses thus appears as a promising therapeutic procedure. There is little
      information about the cell lineages actually forming the NE as they grow
      throughout their days in vitro (DIV). Furthermore, there is no information on how
      good a host the CSF is for grafted NE. Here, we use the HTx rat, a model with
      hereditary hydrocephalus, with the mutation expressed in about 30% of the litter
      (hyHTx), while the littermates develop normally (nHTx). The investigation was
      designed (i) to establish the nature of the cells forming 4 and 6-DIV NE grown
      from NSPCs collected from PN1/nHTx rats and (ii) to study the effects on these
      NEs of CSF collected from nHTx and hyHTx. Immunofluorescence analyses showed that
      90% of cells forming 4-DIV NEs were non-committed multipotential NSPCs, while in
      6-DIV NE, 40% of the NSPCs were already committed into neuronal, glial and
      ependymal lineages. Six-DIV NE further cultured for 3 weeks in the presence of
      fetal bovine serum, CSF from nHTx or CSF from hyHTx, differentiated into neurons,
      astrocytes and betaIV-tubulin+ multiciliated ependymal cells that were joined
      together by adherent junctions and displayed synchronized cilia beating. This
      supports the possibility that ependymal cells are born from subpopulations of NSC
      with their own time table of differentiation. As a whole, the findings indicate
      that the CSF is a supportive medium to host NE and that NE grafted into the CSF
      have the potential to produce neurons, glia and ependyma.

PMID- 29651557
TI  - Higher admission fasting plasma glucose levels are associated with a poorer short
      term neurologic outcome in acute ischemic stroke patients with good collateral
      circulation.
AB  - AIMS: In this retrospective study, we sought to delineate the collateral
      circulation status of acute ischemic stroke patients by CT perfusion and evaluate
      90-day modified Rankin Scale (mRS) scores of patients with good or poor
      collaterals and its correlation with admission fasting plasma glucose (FPG).
      METHODS: We enrolled acute ischemic stroke patients who presented to our hospital
      4.5 h within an onset of the first episode between January 2009 and December
      2015. Neurological assessment was performed using the 90-day mRS scores (0-2 for
      a favorable and 3-6 for an unfavorable neurologic outcome). Relative filling time
      delay (rFTD) was evaluated by CT perfusion scan. The primary outcomes were 90-day
      mRS scores stratified by good (rFTD <= 4 s) versus poor collateral circulation
      (rFTD > 4 s). RESULTS: Totally 270 patients were included, and 139 (51.5%)
      patients achieved a favorable neurologic outcome. One hundred eighty-five (68.5%)
      patients had good collateral circulation. Significantly greater portions of
      patients with good collateral circulation (60.5%, 112/185) achieved a favorable
      neurologic outcome compared to those with poor collateral circulation (31.8%,
      27/85) (P < 0.05). Patients with good collateral circulation achieving a
      favorable neurologic outcome had significantly lower baseline FPG (6.6 +/- 1.96)
      than those with good collateral circulation achieving an unfavorable neurologic
      outcome (8.12 +/- 4.02; P = 0.002). Spearman correlation analysis showed that
      rFTD significantly correlated with 90-day mRS scores (adjusted r = 0.258; P <
      0.001) and admission FPG (r = 0.286; P < 0.001). CONCLUSION: Higher admission FPG
      levels are associated with significantly higher rates of unfavorable neurologic
      outcome of acute ischemic stroke patients with good collateral circulation. FPG
      and rFTD may serve as useful predictors of short-term patient outcome and could
      be used for risk stratification in clinical decision making.

PMID- 29651558
TI  - GlyCulator2: an update on a web application for calculation of glycemic
      variability indices.

PMID- 29651559
TI  - Amperometric determination of ascorbic acid with a glassy carbon electrode
      modified with TiO2-gold nanoparticles integrated into carbon nanotubes.
AB  - A glassy carbon electrode was modified with a TiO2-gold nanoparticle hybrid
      integrated with multi-walled carbon nanotubes in a dihexadecylphosphate film
      (TiO2-Au NP-MWCNT-DHP/GCE) and applied to amperometric determination of ascorbic
      acid (AA). The modified sensor displays fast charge transfer and shows an
      irreversible anodic behavior for AA by cyclic voltammetry. Under optimal
      experimental conditions and using amperometry at 0.4 V, the analytical curve
      presented a statistical linear concentration range for AA from 5.0 to 51 MUmol L
      1, with a limit of detection of 1.2 MUmol L-1. The electrode was successfully
      applied to the determination of AA in pharmaceutical and fruit juice without the
      need for major pretreatment of samples. Graphical abstract Schematic of a new
      sensing platform for ascorbic acid (AA). It is based on a glassy carbon electrode
      (GCE) modified with TiO2-Au nanoparticles integrated into carbon nanotubes in a
      dihexadecylphosphate film. The sensor was applied to amperometric determination
      of AA in juice and pharmaceutical samples.

PMID- 29651560
TI  - Robust photosystem I activity by Cyanothece sp. (Cyanobacteria) and its role in
      prolonged bloom persistence in lake St Lucia, South Africa.
AB  - Worldwide, cyanobacterial blooms are becoming more frequent, exacerbated by
      eutrophication, anthropogenic effects, and global climate change. Environmental
      factors play a direct role in photosynthesis of cyanobacteria and subsequent
      cellular changes, growth, and bloom dynamics. This study investigated the
      photosynthetic functioning of a persistent bloom-forming (18 months)
      cyanobacterium, Cyanothece sp., isolated from Lake St Lucia, South Africa. DUAL
      PAM fluorometric methods were used to observe physiological responses in
      Cyanothece sp. photosystems I and II. Results show that photosystem I activity
      was maintained under all environmental conditions tested, while photosystem II
      activity was not observed at all. Out of the environmental factors tested
      (temperature, salinity, and nitrogen presence), only temperature significantly
      influenced photosystem I activity. In particular, high temperature (40  degrees
      C) facilitated faster electron transport rates, while effects of salinity and
      nitrogen were variable. Cyanothece sp. has shown to sustain bloom status for long
      periods largely because of the essential role of photosystem I activity during
      highly dynamic and even extreme (e.g., salinities higher than 200) environmental
      conditions. This ensures the continual supply of cellular energy (e.g. ATP) to
      important processes such as nitrogen assimilation, which is essential for protein
      synthesis, cell growth and, therefore, bloom maintenance.

PMID- 29651561
TI  - Survival and functional outcome of high tibial osteotomy for medial knee
      osteoarthritis: a 10-20-year cohort study.
AB  - BACKGROUND: The primary aim of this study was to identify independent predictors
      of long-term survivorship after high tibial osteotomy (HTO). The secondary aims
      were to describe the functional outcome of surviving HTO 10-20 years after
      surgery. METHODS: A retrospective cohort of 223 HTO that were performed for the
      treatment of medial osteoarthritis was identified. Details were recorded from the
      patient notes. All surviving patients were contacted and asked to complete a
      Tegner Activity Scale, Lysholm Knee Score and rate pain using the Visual Analogue
      Scale (VAS). Survival analysis was performed, using conversion to arthroplasty as
      the definition of failure. RESULTS: The mean age was 54 years (24-80 years).
      There were 123 (55.2%) in males and 100 (44.8%) in females. The mean BMI was 27.2
      (SD 3.9). Twenty (9%) patients were lost to follow-up. The mean follow-up was 12
      (SD 4) years. Survival at 10 years was 75 and 55% at 15 years and less than 40%
      at 20 years. Cox regression analysis demonstrated age of 50 years or more, female
      gender and surgical technique to be significant independent predictors of
      failure. The median Tegner score was 3 (inter-quartile range (IQR) 1-3). The mean
      Lysholm score was 75.5 (SD 18.4). The median VAS was 5 (IQR 0-6). CONCLUSIONS:
      The medium- to long-term survival and functional outcome after HTO was good to
      excellent at 10-20 years of follow-up. Age, gender, surgeon and surgical
      technique were identified as independent predictors of failure.

PMID- 29651562
TI  - The evaluation of E. faecalis colonies dissolution ability of sodium hypochlorite
      in microenvironment by a novel device.
AB  - Enterococcus faecalis(E. faecalis) is a common microorganism could be isolated
      from the infected canals, especially in the case of refractory apical
      periodontitis. Due to its ability to invade the dentinal tubules and highly
      resistant to antimicrobial strategies, the thorough debridement of E.faecalis is
      hard to achieve. And that may be one of the reasons to cause reinfection and
      therapeutic failure. According to the anatomy of dentinal tubules published
      before and the results of our team previous work, we designed six types of
      microtubes with different sizes. By using the method of centrifugation and
      incubation, a standard infected model mimicking dentinal tubules was established.
      Sodium hypochlorite (NaClO) is the most popular irrigant applied in root canal
      treatment. We used three different concentrations with four distinct irrigation
      duration to observe the antibacterial process of E. faecalis colonies within
      microtubes dynamically. We concluded that the role of NaClO in the microtubes is
      concentration dependent and duration dependent. And the interpretation of the
      results has a certain reference value for clinicians.

PMID- 29651563
TI  - Predictors of decompressive hemicraniectomy in malignant middle cerebral artery
      stroke.
AB  - Identification of factors in malignant middle cerebral artery (MMCA) stroke
      patients that may be useful in selecting patients for DHC. This study was a
      retrospective multicenter study of patients referred for DHC based on the
      criteria of the randomized control trials of DHC in MMCA stroke. Demographic,
      clinical, and radiology data were analyzed. Patients who underwent DHC were
      compared to those who survived without surgery. Two hundred three patients with
      MMCA strokes were identified: 137 underwent DHC, 47 survived without DHC, and 19
      refused surgery and died. Multivariate analysis identified the following factors
      determining DHC in MMCA stroke: age < 55 years (OR 8.5, 95% CI 3.3-22.1, P <
      0.001), MCA with involvement of additional vascular territories (anterior
      cerebral artery, posterior cerebral artery (OR 4.8, 95% CI 1.5-14.9, P = 0.007),
      septum pellucidum displacement >= 7.5 mm (OR 4.8, 95% CI 1.9-11.7, P = 0.001),
      diabetes (OR 3.7, 95% CI 1.3-10.6, P = 0.012), infarct growth rate (IGR) ml/h (OR
      1.11, 95% CI 1.02-1.2, P = 0.015), and temporal lobe involvement (OR 2.5, 95% CI
      1.01-6.1, P = 0.048). The internal validation of the multivariate logistic
      regression model using bootstrapping analysis showed marginal bias. Among
      patients with MMCA infarctions, an increased possibility of DHC is associated
      with younger age, MCA with additional infarction, septum pellucidum deviation of
      > 7.5 mm, diabetes, IGR, and temporal lobe involvement. The presence of these
      risk factors identifies those MMCA stroke patients who may require DHC.
      Bootstrapping analysis indicated the model is good enough to predict the outcome
      in general population.

PMID- 29651564
TI  - Impedance Analysis of Thin Films of Organic-Inorganic Perovskites CH3NH3PbI3 with
      Control of Microstructure.
AB  - The effect of starting reagents (PbI2:{CH3NH3I + CH3NH3Cl}) with different ratios
      in raw solutions on the microstructure of films of organic-inorganic perovskites
      CH3NH3PbI3-xClx, as well as on the electrical properties, has been investigated.
      It was found that the crystallinity is increased sharply when the ratio of the
      starting reagents increases from 1:1 to 1:2 and is changed slightly with a
      further increase of ratio to 1:3. It is shown that when the ratio of starting
      reagents varies, the morphology of the films changes; at a ratio of 1:1, the
      films consist of needle-like particles, and when the ratio is increased,
      particles become roundish and then faceted. Additionally, the average grain size
      is decreased. Complex impedance curves and I-V curves have been investigated for
      samples with different ratios of the starting reagents. With increasing this
      ratio, the concentration of charge carriers remains unchanged, the mobility of
      charge carriers decreases, and conductivity passes through a maximum at a ratio
      of 1:2. The electrical properties of film are the highest at the ratio of
      starting reagents 1:2 due to the effect of two competing factors: the growth of
      crystallinity and the decrease of grain size.

PMID- 29651565
TI  - Synthesis and preclinical evaluation of novel 18F-labeled Glu-urea-Glu-based PSMA
      inhibitors for prostate cancer imaging: a comparison with 18F-DCFPyl and 18F-PSMA
      1007.
AB  - BACKGROUND: Due to its high and consistent expression in prostate cancer (PCa),
      the prostate-specific membrane antigen (PSMA) represents an ideal target for
      molecular imaging and targeted therapy using highly specific radiolabeled PSMA
      ligands. To address the continuously growing clinical demand for 18F-labeled PSMA
      probes, we developed two novel Glu-urea-Glu-(EuE)-based inhibitors, EuE-k-18F
      FBOA (1) and EuE-k-beta-a-18F-FPyl (2), both with optimized linker structure and
      different 18F-labeled aromatic moieties. The inhibitors were evaluated in a
      comparative preclinical study with 18F-DCFPyl and 18F-PSMA-1007. RESULTS:
      Radiolabeling procedures allowed preparation of (1) and (2) with high
      radiochemical yields (67 +/- 7 and 53 +/- 7%, d.c.) and purity (> 98%). When
      compared with 18F-DCFPyl (IC50 = 12.3 +/- 1.2 nM) and 18F-PSMA-1007 (IC50 = 4.2
      +/- 0.5 nM), both metabolically stable EuE-based ligands showed commensurable or
      higher PSMA affinity (IC50 = 4.2 +/- 0.4 nM (1), IC50 = 1.1 +/- 0.2 nM (2)).
      Moreover, 1.4- and 2.7-fold higher internalization rates were observed for (1)
      and (2), respectively, resulting in markedly enhanced tumor accumulation in LNCaP
      tumor-bearing mice ((1) 12.7 +/- 2.0% IA/g, (2) 13.0 degrees  +/- 1.0% IA/g vs.
      7.3 +/- 1.0% IA/g (18F-DCFPyl), 7.1 +/- 1.5% IA/g (18F-PSMA-1007), 1 h p.i.). In
      contrast to (1), (2) showed higher kidney accumulation and delayed clearance
      kinetics. Due to the high hydrophilicity of both compounds, almost no unspecific
      uptake in non-target tissue was observed. In contrast, due to the less
      hydrophilic character (logP = - 1.6) and high plasma protein binding (98%), 18F
      PSMA-1007 showed uptake in non-target tissue and predominantly hepatobiliary
      excretion, whereas, 18F-DCFPyl exhibited pharmacokinetics quite similar to those
      obtained with (1) and (2). CONCLUSION: Both 18F-labeled EuE-based PSMA ligands
      showed excellent in vitro and in vivo PSMA-targeting characteristics. The
      substantially higher tumor accumulation in mice compared to recently introduced
      18F-PSMA-1007 and 18F-DCFPyl suggests their high value for preclinical studies
      investigating the effects on PSMA-expression. In contrast to (2), (1) seems to be
      more promising for further investigation, due to the more reliable 18F-labeling
      procedure, the faster clearance kinetics with comparable high tumor uptake,
      resulting therefore in better high-contrast microPET imaging as early as 1 h p.i.

PMID- 29651566
TI  - Clinical evaluation of the aberrant left hepatic artery arising from the left
      gastric artery in esophagectomy.
AB  - PURPOSE: The left gastric artery (LGA) is commonly severed when the gastric tube
      is made for esophageal reconstruction. Sacrifice of the LGA can cause liver
      ischemic necrosis in patients with an aberrant left hepatic artery (ALHA) arising
      from the LGA. We experienced a case of life-threatening hepatic abscess after
      severing the ALHA. Therefore, the purpose of this study is to evaluate clinical
      outcomes of severing the ALHA. METHODS: We retrospectively enrolled 176
      consecutive patients who underwent esophagectomy with gastric tube
      reconstruction. They were classified into the ALHA (N = 16, 9.1%) and non-ALHA (N
      = 160, 90.9%) groups. Univariate analysis was performed to compare the
      clinicopathological variables. Long-term survival was analyzed using the Kaplan
      Meier method in matched pair case-control analysis. RESULTS: The postoperative
      morbidities were not statistically different between the two groups, although
      serum alanine aminotransferase levels on postoperative days 1 and 3 were
      significantly higher in the ALHA group (36 IU/L, 14-515; 32 IU/L, 13-295) than in
      the non-ALHA group (24 IU/L, 8-163; 19 IU/L, 6-180), respectively (p = 0.0055; p
      = 0.0073). Overall survival was not statistically different between the two
      groups (p = 0.26). CONCLUSIONS: Severe hepatic abscess occurred in 6.3% of the
      patients with the ALHA after esophagectomy, even though the results presented
      here found no statistical differences in morbidity or mortality with or without
      the ALHA. Surgeons should probably attempt to preserve the ALHA especially in
      patients with altered liver function while making a gastric tube for esophageal
      reconstruction.

PMID- 29651567
TI  - The origin of the medial femoral circumflex artery, lateral femoral circumflex
      artery and obturator artery.
AB  - INTRODUCTION: The most significant blood vessel supplying the hip joint is the
      medial femoral circumflex artery (MFCA). MFCA with lateral femoral circumflex
      artery (LFCA) are the first branches of the deep femoral artery (DFA) or they
      originate directly from the common femoral artery (CFA) or superficial femoral
      artery (SFA). PURPOSE AND METHODS: We analyzed 100 CT angiogram of the hip region
      [72 men, 28 women; mean age 46.4 (14-80)] to assess the frequency of each type of
      division of the MFCA and LFCA from either the DFA or directly from the CFA or
      SFA. To assess the variations on each side in one individual we analyzed both
      hips in 73 patients [mean age 46.6 (14-80)]. RESULTS: Many different types of
      division have been described. The most frequent one in which both the MFCA and
      LFCA originate from the DFA, was observed in 50% of patients. In 31% of hips the
      MFCA originates from the CFA. In our study, a normal origin of the obturator
      artery from the internal iliac artery was observed in 67% of patients and an
      atypical origin, called corona mortis was observed in 33% of patients.
      CONCLUSIONS: The deep branch of the MFCA is the main artery supplying the femoral
      head, it is at risk during surgical approach to the hip joint. The atypical
      anastomosis called corona mortis is also at risk while performing the approach to
      pubic bone. Therefore, knowledge of their topography is very important.

PMID- 29651568
TI  - Dorsal extensions of the fastigium cerebelli: an anatomical study using magnetic
      resonance imaging.
AB  - BACKGROUND AND PURPOSE: The fastigium cerebelli is an important topographical
      landmark for neurosurgeons and radiologists. However, few studies have
      characterized the morphology of the fastigium cerebelli. We aimed to investigate
      the fastigium cerebelli using postmortem specimens and magnetic resonance imaging
      (MRI) in vivo. MATERIALS AND METHODS: Three cadaveric brains were midsagittally
      sectioned for observing the fastigium cerebelli. Additionally, 66 outpatients
      underwent MRI, including sagittal T1-weighted imaging, axial T2-weighted imaging,
      and coronal constructive interference in steady-state (CISS) sequence. RESULTS:
      In the cadaveric specimens, the fastigium cerebelli was observed as a beak-like
      dorsal protrusion of the fourth ventricle. Its inner surface was observed as a
      small fovea. On serial CISS images, the fastigium cerebelli consistently
      possessed a pair of triangular-shaped, dorsal extensions lying parasagittally
      along the nodule. These extensions were classified as symmetrical, right-side
      dominant, or left-side dominant. The symmetrical type was the most predominant
      and comprised 60.6% of the extensions, while the right-side dominant and left
      side dominant types comprised 13.6 and 25.8%, respectively. In 91% of the 66
      patients, the number of slices covering the entirety of the dorsal extensions
      were the same on both sides. The fastigial angle (theta) formed by lines tangent
      to the superior and inferior medullary velums varied widely. CONCLUSIONS: The
      fastigium cerebelli has a pair of dorsal extensions lying parasagittally along
      the nodule. Coronal CISS sequence is useful in delineating the fastigium
      cerebelli in vivo.

PMID- 29651569
TI  - External radiation exposure, excretion, and effective half-life in 177Lu-PSMA
      targeted therapies.
AB  - BACKGROUND: Prostate-specific membrane antigen (PSMA)-targeted therapy with 177Lu
      PSMA-617 is a therapeutic option for patients with metastatic castration
      resistant prostate cancer (mCRPC). To optimize the therapy procedure, it is
      necessary to determine relevant parameters to define radiation protection and
      safety necessities. Therefore, this study aimed at estimating the ambient
      radiation exposure received by the patient. Moreover, the excreted activity was
      quantified. RESULTS: In total, 50 patients with mCRPC and treated with 177Lu-PSMA
      617 (mean administered activity 6.3 +/- 0.5 GBq) were retrospectively included in
      a bi-centric study. Whole-body dose rates were measured at a distance of 2 m at
      various time points after application of 177Lu-PSMA-617, and effective half-lives
      for different time points were calculated and compared. Radiation exposure to the
      public was approximated using the dose integral. For the estimation of the
      excreted activity, whole body measurements of 25 patients were performed at 7
      time points. Unbound 177Lu-PSMA-617 was rapidly cleared from the body. After 4 h,
      approximately 50% and, after 12 h, approximately 70% of the administered activity
      were excreted, primarily via urine. The mean dose rates were the following: 3.6
      +/- 0.7 MUSv/h at 2 h p. i., 1.6 +/- 0.6 MUSv/h at 24 h, 1.1 +/- 0.5 MUSv/h at 48
      h, and 0.7 +/- 0.4 MUSv/h at 72 h. The mean effective half-life of the cohort was
      40.5 +/- 9.6 h (min 21.7 h; max 85.7 h). The maximum dose to individual members
      of the public per treatment cycle was ~ 250 +/- 55 MUSv when the patient was
      discharged from the clinic after 48 h and ~ 190 +/- 36 MUSv when the patient was
      discharged after 72 h. CONCLUSIONS: In terms of the radiation exposure to the
      public, 177Lu-PSMA is a safe option of radionuclide therapy. As usually four
      (sometimes more) cycles of the therapy are performed, it must be conducted in a
      way that ensures that applicable legal requirements can be followed. In other
      words, the radiation exposure to the public and the concentration of activity in
      wastewater must be sub-marginal. Therefore, in certain countries, hospitalization
      of these patients is mandatory.

PMID- 29651570
TI  - Thickness-dependent Magnetic and Microwave Resonance Characterization of Combined
      Stripe Patterned FeCoBSi Films.
AB  - In this paper, we fabricated a series of FeCoBSi multistoried patterned magnetic
      films with different thickness by traditional UV lithography method and DC
      sputtering deposition. Broad resonance band phenomenon was observed during high
      frequency property characterization, with full width half maximum (FWHM) of 4 GHz
      when the film thickness is 45 nm. The broad resonance band effect was contributed
      to the existence of multiple resonance peaks due to different stripe width of the
      combined stripe pattern, which induced distinguish shape anisotropic field in
      each stripe. Each resonance peak was independent due to the gap between the
      stripes, leading to a controllable method to tune the microwave properties of
      such structure. With thickness varied, the resonance band could be altered
      according to the mathematic prediction. This work presents an effective method
      for tuning the microwave resonance characterization in magnetization dynamic.

PMID- 29651571
TI  - Correlation of neuropsychological and metabolic changes after epilepsy surgery in
      patients with left mesial temporal lobe epilepsy with hippocampal sclerosis.
AB  - BACKGROUND: Epilepsy surgery often causes changes in cognition and cerebral
      glucose metabolism. Our aim was to explore relationships between pre- and
      postoperative cerebral metabolism as measured with 18F-fluorodeoxyglucose
      positron emission tomography (FDG-PET) and neuropsychological test scores in
      patients with left mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE
      HS), who were rendered seizure-free after epilepsy surgery. RESULTS: Thirteen
      patients were included. All had neuropsychological testing and an interictal FDG
      PET scan of the brain pre- and postoperative. Correlations between changes in
      neuropsychological test scores and metabolism were examined using statistical
      parametric mapping (SPM). There were no significant changes in the
      neuropsychological test scores pre- and postoperatively at the group level.
      Decreased metabolism was observed in the left mesial temporal regions and
      occipital lobe. Increased metabolism was observed in the bi-frontal and right
      parietal lobes, temporal lobes, occipital lobes, thalamus, cerebellum, and
      vermis. In these regions, we did not find a correlation between changes in
      metabolism and neuropsychological test scores. A significant negative
      correlation, however, was found between metabolic changes in the precuneus and
      Boston Naming Test (BNT) scores. CONCLUSIONS: There are significant metabolic
      decreases in the left mesial temporal regions and increases in the bi-frontal
      lobes; right parietal, temporal, and occipital lobes; right thalamus; cerebellum;
      and vermis in patients with left MTLE-HS who were rendered seizure-free after
      epilepsy surgery. We could not confirm that these changes translate into
      significant cognitive changes. A significant negative correlation was found
      between changes in confrontation naming and changes in metabolism in the
      precuneus. We speculate that the precuneus may play a compensatory role in
      patients with postoperative naming difficulties after left TLE surgery.
      Understanding of these neural mechanisms may aid in designing cognitive
      rehabilitation strategies.

PMID- 29651572
TI  - Antiproteinuric effects of renin-angiotensin inhibitors in lung cancer patients
      receiving bevacizumab.
AB  - PURPOSE: The objective of this study was to investigate the effect of renin
      angiotensin system inhibitors (RASIs) on bevacizumab (BV)-induced proteinuria in
      non-small cell lung cancer (NSCLC) patients. MATERIALS AND METHODS: We
      retrospectively reviewed the medical records of NSCLC patients receiving BV
      between 2008 and 2014 at 11 hospitals. The patients were categorized into three
      groups according to their antihypertensive drug use: RASI user, non-RASI user,
      and non-user groups. The primary outcome was a proteinuria event of any grade
      during the first 6 cycles of BV treatment. RESULTS: A total of 211 patients were
      included, 89 of whom received antihypertensive drugs. Of these 89 patients, 49
      were in the RASI user group, and 40 were in the non-RASI user group. The non-user
      group comprised 122 patients. The occurrence of proteinuria in the RASI user
      group was significantly lower than that in the non-RASI user group (P = 0.037)
      but was not significantly lower than that in the non-user group (P = 0.287).
      Patients using RASIs had a lower rate of proteinuria than those who did not use
      RASIs according to multivariate analysis (odds ratio 0.32; 95% confidence
      interval 0.12-0.86; P = 0.024). CONCLUSION: Our study suggests that RASI
      administration reduces the risk of proteinuria in patients receiving BV.

PMID- 29651573
TI  - Metabolic syndrome in systemic lupus erythematosus patients : Relationship to
      disease activity and neuropsychiatric lupus.
AB  - OBJECTIVE: The study aims to evaluate the presence of metabolic syndrome (MetS)
      among Egyptian systemic lupus erythematosus (SLE) patients. Additionally, we
      intended to determine the association of MetS with disease activity, clinical and
      laboratory features. PATIENTS AND METHODS: This cross-sectional study included
      adult SLE patients diagnosed and followed in rheumatology outpatient clinics. The
      demographic data, clinical and laboratory parameters were assessed for all
      patients. Disease activity was measured using SLE Disease Activity Index (SLEDAI
      2k). Patients were diagnosed to have MetS according to The National Cholesterol
      Education Program Adult Treatment Panel III (NCEP). The characteristics of SLE
      patients and their disease status were compared between those with and without
      MetS. RESULTS: A total of 74 SLE patients were included; mean age was 32.1 +/-
      10.9 years and 87.8% were females. Twenty-five (33.8%) SLE patients had
      neuropsychiatric lupus (NPSLE), with headache the most common manifestation. MetS
      was diagnosed in 45.9% of the SLE group. Patients with MetS had significantly
      older age, delayed age of diagnosis and higher SLEDAI-2k scores (p = 0.015, p =
      0.014 and p = 0.019, respectively) compared to those without MetS. NPSLE was
      significantly correlated with MetS (r = 0.32, p = 0.006) and in particular with
      higher central obesity (r = 0.43, p < 0.001). In the multivariate analysis, NPSLE
      remained independently associated with MetS (OR = 4.9, p = 0.004, 95% CI = 1.7
      14.4). CONCLUSION: Metabolic syndrome is present in a significant proportion of
      Egyptian patients with adult SLE. Delayed disease diagnosis and higher disease
      activity are SLE-related factors that may contribute to increase the risk of
      MetS. Data suggest that neuropsychiatric lupus may underlie some of the increased
      risk for MetS and central obesity.

PMID- 29651574
TI  - Nocturnal blood pressure dipping is similar in rheumatoid arthritis patients as
      compared to a normal population.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory
      disorder which further doubles the risk of developing cardiovascular disease.
      Some studies suggest that in RA patients, the prevalence of hypertension
      increases due to prednisolone use, clinical status, genetic factors, and physical
      inactivity. On the other hand, dipper and non-dipper status in RA patients
      compared to non-RA subjects has not been investigated to our knowledge. Purpose
      of the study is to investigate whether non-dipper status is more deteriorated in
      RA patients. METHODS: Sixty-five RA patients and 61 age-sex-matched control
      patients were evaluated in this cross-sectional study. Patients were classified
      according to 24-h ambulatory blood pressure monitoring results. Patients with
      previous hypertension diagnosis, coronary artery disease, and abnormal kidney
      function were excluded. RESULTS: Mean age of the study sample was 53.7 +/- 12.3
      years and 40.5% were male. There was no significant difference between groups in
      terms of basic demographic characteristics. Leukocyte counts (p = 0.001),
      neutrophil counts (p = 0.001), and red cell distribution width (p = 0.000) were
      significantly higher in the RA group. ABPM results indicate no significant
      difference between RA patients and the control group in terms of daytime systolic
      and diastolic blood pressure, nighttime systolic and diastolic blood pressure,
      and average systolic and diastolic blood pressure results (p > 0.05). There was
      no statistical difference regarding the non-dipper status of patient groups (p =
      0.412). Nocturnal blood pressure dipping was significantly similar between groups
      (p = 0.980). CONCLUSION: In conclusion, RA patients have similar values in terms
      of nocturnal blood pressure dipping and hypertension diagnosis as compared to
      normal population.

PMID- 29651575
TI  - Assessment of pelvic tilt in anteroposterior radiographs by means of tilt ratios.
AB  - INTRODUCTION: In anteposterior (AP) radiographs, cup position in total hip
      arthroplasty and acetabular anatomy in hip-preserving surgery are highly
      influenced by pelvic tilt. The sagittal rotation of the anterior pelvic plane is
      an important measurement of pelvic tilt during hip surgery. Thus, correct
      evaluation of cup position and acetabular parameters requires the assessment of
      pelvic tilt in AP radiographs. METHODS: Changes in pelvic tilt inversely change
      the height of the lesser pelvis and the obturator foramen in AP radiographs. Tilt
      ratios were calculated by means of these two parameters in simulated radiographs
      for ten male and ten female pelvises in defined tilt positions. A tilt formula
      obtained by exponential regression analysis was evaluated by two blinded
      investigators by means of 14 simulated AP radiographs of the pelvis with pelvic
      tilts ranging from + 15 degrees  to - 15 degrees . RESULTS: No differences were
      found between male and female tilt ratios for each 5 degrees  step of simulated
      pelvic tilt. Pelvic tilt and tilt ratios correlated exponentially. Using the tilt
      formula, the two blinded investigators were able to assess pelvic tilt with high
      conformity, a mean relative error of + 0.4 degrees  (SD +/- 4.6 degrees ), and a
      mean absolute error of 3.9 degrees  (SD +/- 2.3 degrees ). Neutral pelvic tilt is
      indicated by a tilt ratio of 0.5 when the height of the lesser pelvis is twice
      the height of the obturator foramen. CONCLUSION: The analysis and interpretation
      of cup position and acetabular parameters may be improved by our method for
      assessing pelvic tilt in AP radiographs.

PMID- 29651576
TI  - Fluorescence Molecular Imaging and Tomography of Matrix Metalloproteinase
      Activatable Near-Infrared Fluorescence Probe and Image-Guided Orthotopic Glioma
      Resection.
AB  - PURPOSE: Malignant gliomas are major causes of cancer-related mortality and
      morbidity. Traditional surgery usually leads to incomplete resection of gliomas
      resulting in the high incidence of tumor recurrence. Advanced medical imaging
      technology, such as fluorescence imaging-guided surgery, combined with tumor
      specific imaging probes allows the identification of tumor margins and improved
      surgery. However, there are two pressing issues that need to be addressed: first,
      few fluorescence imaging probes can specifically target gliomas; second,
      fluorescence molecular imaging (FMI) cannot get the in-depth information of deep
      seated gliomas; both of which affect the complete removal of the gliomas.
      PROCEDURES: In this study, the biodistribution of smart matrix metalloproteinase
      (MMP) targeting near-infrared (NIR) fluorescent probe MMPSense 750 FAST (MMP-750)
      was examined in both U87MG-GFP-fLuc glioma xenograft and orthotopic mouse models
      using FMI. Then, CT and FMI images of orthotopic gliomas were acquired for the
      reconstruction of fluorescence molecular tomography (FMT) using a randomly
      enhanced adaptive subspace pursuit (REASP) algorithm. Furthermore, the resection
      of orthotopic glioma was performed using the fluorescence surgical navigation
      system after the injection of the MMP-750 probe. After surgery, bioluminescence
      imaging (BLI) and hematoxylin and eosin staining were carried out to confirm the
      precision resection of the tumor. RESULTS: FMI results showed that the MMP-750
      probe can specifically target U87MG glioma in vivo. FMT presented the spatial
      information of the orthotopic glioma using the REASP reconstruction algorithm.
      Furthermore, MMP-750 could effectively delineate the tumor margin during glioma
      surgery leading to a complete resection of the tumors. CONCLUSIONS: The smart MMP
      750 specifically targets the glioma and FMT of MMP-750 provides 3D information
      for the spatial localization of the glioma. MMP-750 can work as an ideal
      fluorescence probe for guiding the intraoperative surgical resection of the
      glioma, possessing clinical translation.

PMID- 29651578
TI  - Arms Down Cone Beam CT Hepatic Angiography: Are We Focusing on the Wrong Target?

PMID- 29651577
TI  - Pathological Margin Clearance and Survival After Pancreaticoduodenectomy in a US
      and European Pancreatic Center.
AB  - BACKGROUND: The optimal definition of a margin-negative resection and its exact
      prognostic significance on survival in resected pancreatic adenocarcinoma remains
      unknown. This study was designed to assess the relationship between pathological
      margin clearance, margin type, and survival. METHODS: Patients who underwent
      pancreaticoduodenectomy with curative intent at two academic institutions, in
      Amsterdam, the Netherlands, and Boston, Massachusetts, between 2000 and 2014 were
      retrospectively evaluated. Overall survival, recurrence rates, and progression
      free survival (PFS) were assessed by Kaplan-Meier estimates and multivariate Cox
      proportional hazards analysis, according to pathological margin clearance and
      type of margin involved. RESULTS: Of 531 patients identified, the median PFS was
      12.9, 15.4, and 24.1 months, and the median overall survival was 17.4, 22.9, and
      27.7 months for margin clearances of 0, < 1, and >=1 mm, respectively (all log
      rank p < 0.001). On multivariate analysis, patients with a margin clearance of
      >=1 mm demonstrated a survival advantage relative to those with 0 mm clearance
      [hazard ratio (HR) 0.71, p < 0.01], whereas survival was comparable for patients
      with a margin clearance of < 1 mm versus 0 mm (HR: 0.93, p = 0.60). Patients with
      involvement (0 or < 1 mm margin clearance) of the SMV/PV margin demonstrated
      prolonged median overall survival (25.7 months) relative to those with SMA
      involvement (17.5 months). CONCLUSIONS: In patients undergoing
      pancreaticoduodenectomy for pancreatic adenocarcinoma, a margin clearance of >=1
      mm correlates with improved survival relative to < 1 mm clearance and may be a
      more accurate predictor of a complete margin-negative resection in pancreatic
      cancer. The type of margin involved also appears to impact survival.

PMID- 29651579
TI  - Percutaneous Radiofrequency Ablation for the Treatment of Osteoid Osteoma in
      Children and Adults: A Comparative Analysis in 92 Patients.
AB  - PURPOSE: To compare technical success, complications, and long-term clinical
      success following radiofrequency ablation of osteoid osteomas in pediatric and
      adult patients. MATERIALS AND METHODS: Ninety-two patients underwent percutaneous
      computed tomography-guided radiofrequency ablation for osteoid osteomas including
      54 pediatric (mean age 12.9 years) and 38 adult (mean age 24.1 years) patients.
      Presenting indication, osteoma location, ablation method, technical success,
      complications, visual analog score, radiographic follow-up, clinical success,
      reintervention rate, and total follow-up were reported. Technical success was
      defined as placement of the probe in the radiolucent nidus with ablation.
      Clinical success was defined as resolution of symptoms. RESULTS: Ablation
      indications included: pain localized to the lesion, night pain, and an osteoma on
      imaging in all patients. Majority of osteoid osteomas were localized to the femur
      (pediatric [n = 22, 40.7%]; adult [n = 12, 34.2%]) and tibia (pediatric [n = 21,
      38.9%]; adult [n = 10, 26.3%]). Mean lesion size was 9.6 mm in pediatric patients
      and 9.0 mm in adults. Technical success was achieved in all pediatric patients
      (100%) and 97.4% of adults. Two complications occurred. Primary clinical success
      was achieved in 49 (90.7%) pediatric and 35 (92.1%) adult patients. Five (9.3%)
      pediatric and 3 (7.9%) adult patients sought reintervention for residual
      symptoms, and all had secondary clinical success. Mean total follow-up was 95.2
      +/- 58.7 months in pediatric and 90.0 +/- 61.6 months in adult patients. No
      differences in outcomes were identified between pediatric and adult patients.
      CONCLUSION: Radiofrequency ablation of osteoid osteomas is safe with excellent
      technical and clinical success rates in pediatric and adult patients.

PMID- 29651580
TI  - Hepatotoxic Dose Thresholds by Positron-Emission Tomography After Yttrium-90
      Radioembolization of Liver Tumors: A Prospective Single-Arm Observational Study.
AB  - PURPOSE: To define a threshold radiation dose to non-tumoral liver from 90Y
      radioembolization that results in hepatic toxicity using pair-production PET.
      MATERIALS AND METHODS: This prospective single-arm study enrolled 35 patients
      undergoing radioembolization. A total of 34 patients (27 with HCC and 7 with
      liver metastases) were included in the final analysis. Of 27 patients with
      underlying cirrhosis, 22 and 5 patients were Child-Pugh A and B, respectively.
      Glass and resin microspheres were used in 32 (94%) and 2 (6%) patients,
      respectively. Lobar and segmental treatment was done in 26 (76%) and 8 (24%)
      patients, respectively. Volumetric analysis was performed on post
      radioembolization time-of-flight PET imaging to determine non-tumoral parenchymal
      dose. Hepatic toxicity was evaluated up to 120 days post-treatment, with CTCAE
      grade <= 1 compared to grade >= 2. RESULTS: The median dose delivered to the non
      tumoral liver in the treated lobe was 49 Gy (range 0-133). A total of 15 patients
      had grade <= 1 hepatic toxicity, and 19 patients had grade >= 2 toxicity.
      Patients with a grade >= 2 change in composite toxicity (70.7 vs. 43.8 Gy),
      bilirubin (74.1 vs. 43.3 Gy), albumin (84.2 vs. 43.8 Gy), and AST (94.5 vs. 47.1
      Gy) have significantly higher non-tumoral parenchymal doses than those with grade
      <= 1. Liver parenchymal dose and Child-Pugh status predicted grade >= 2 toxicity,
      observed above a dose threshold of 54 Gy. CONCLUSION: Increasing delivered 90Y
      dose to non-tumoral liver measured by internal pair-production PET correlates
      with post-treatment hepatic toxicity. The likelihood of toxicity exceeds 50% at a
      dose threshold of 54 Gy. ClinicalTrials.gov identifier: NCT02848638.

PMID- 29651581
TI  - Single 15-Min Protocol Yields the Same Cryoablation Size and Margin as the
      Conventional 10-8-10-Min Protocol: Results of Kidney and Liver Swine Experiment.
AB  - INTRODUCTION: The objective was to determine the ablation size of a single 15-min
      freeze and compare it with the conventional 10-min freeze-8-min thaw-10-min
      freeze protocol. Secondary objectives were to determine the ablation margin and
      to ascertain whether islands of viable tissue remain within the ablation zone.
      MATERIALS AND METHODS: Five adult swine under general anesthesia were used. After
      surgical abdominal exposure, two ablations were performed in liver and two in
      kidney. One ablation utilized the 15-min and the second the 10-8-10-min protocol.
      At maximum ice-ball, tissue ink was infused via an angiographic catheter in
      hepatic or renal artery to stain the non-frozen tissue. Animals were euthanized
      and organs examined macro- and microscopically. RESULTS: Three histological
      regions were observed: (A) a viable/stained region representing the tissue
      outside the ice-ball, (B) a central necrotic area representing the ablated region
      within the ice-ball and (C) an unstained but viable margin representing the non
      lethal margin within ice-ball. Ablation size did not vary with protocol but did
      for tissue type. Renal ablation was approximately 5 * 4 cm with both protocols,
      whereas liver ablation was approximately 6.7 * 4.4 cm. Ablation margin was
      measured at 1 mm irrespective of ablation protocol or tissue. No islands of
      viable tissue were identified within the ablation zone. DISCUSSION: Fifteen
      minute cryoablation yielded an ablation size and margin identical to that of the
      conventional 10-8-10-min protocol. Within the ablated region, cell death was
      uniform. The only difference was a larger cryoablation zone in hepatic tissue
      compared to renal tissue, likely attributable to differences in blood perfusion.

PMID- 29651583
TI  - Food Bolus Impaction in the Era of Increased EoE Recognition: Push and Pull,
      Biopsy and Dilate Before It Is Too Late.

PMID- 29651582
TI  - Methods for identification of spike patterns in massively parallel spike trains.
AB  - Temporally, precise correlations between simultaneously recorded neurons have
      been interpreted as signatures of cell assemblies, i.e., groups of neurons that
      form processing units. Evidence for this hypothesis was found on the level of
      pairwise correlations in simultaneous recordings of few neurons. Increasing the
      number of simultaneously recorded neurons increases the chances to detect cell
      assembly activity due to the larger sample size. Recent technological advances
      have enabled the recording of 100 or more neurons in parallel. However, these
      massively parallel spike train data require novel statistical tools to be
      analyzed for correlations, because they raise considerable combinatorial and
      multiple testing issues. Recently, various of such methods have started to
      develop. First approaches were based on population or pairwise measures of
      synchronization, and later led to methods for the detection of various types of
      higher-order synchronization and of spatio-temporal patterns. The latest
      techniques combine data mining with analysis of statistical significance. Here,
      we give a comparative overview of these methods, of their assumptions and of the
      types of correlations they can detect.

PMID- 29651585
TI  - Ruptured Fusiform Aneurysm of the Anterior Spinal Artery : Successful Treatment
      with Flow Diverter Stent Placed in the Feeding Vertebral Artery.

PMID- 29651584
TI  - Anxiety and depression associated with tyrosine kinase inhibitor discontinuation
      in patients with chronic myeloid leukemia.
AB  - BACKGROUND: ABL tyrosine kinase inhibitors (TKIs) significantly changed the
      prognosis of patients with chronic myeloid leukemia (CML), and clinical trials
      demonstrated that TKIs can be discontinued in approximately 50% of patients after
      a period of deep molecular response (DMR). However, in some patients, TKI
      discontinuation leads to anxiety and depression. Here, we analysed the incidence
      of anxiety and depression in patients who stop TKI therapy. METHODS: Anxiety and
      depression were evaluated using the Hospital Anxiety and Depression Scale (HADS)
      in 32 patients with CML. The survey periods were at TKI discontinuation, at 1, 6,
      12, and 24 months and at reintroduction of TKIs. The HADS score at the initial
      TKI discontinuation was compared between patients within and outside clinical
      trials. Treatment-free remission (TFR) rates outside clinical trials were
      evaluated. RESULTS: The HADS scores were significantly higher at TKI
      reintroduction after molecular relapse than at the initial TKI discontinuation
      (at the initiation of stopping TKIs vs. at reintroduction of TKIs, 8.47 +/- 5.53
      vs. 1.67 +/- 2.26; p = 0.0003). The TFR rate at 12 months after stopping TKIs
      outside clinical trials was 55.6%. The HADS score at the initial TKI
      discontinuation did not differ between patients within and outside clinical
      trials. CONCLUSION: Stopping TKIs outside clinical trials is feasible if the
      guidelines for stopping are followed and an adequate monitoring system is
      available. Discontinuation of TKIs requires adequate management of anxiety and
      depression.

PMID- 29651586
TI  - Revascularization Techniques for Acute Basilar Artery Occlusion : Technical
      Considerations and Outcome in the Setting of Severe Posterior Circulation Steno
      Occlusive Disease.
AB  - PURPOSE: To describe the clinical and radiological characteristics, frequency,
      technical aspects and outcome of endovascular treatment of acute basilar artery
      occlusion (ABO) in the setting of vertebrobasilar steno-occlusive disease.
      METHODS: Retrospective analysis of databases of two universitary stroke centers
      including all consecutive patients from January 2013 until May 2017 undergoing
      thrombectomy for a) acute stroke due to basilar artery occlusion and either
      significant basilar artery stenosis or vertebral artery stenosis/occlusion as
      well as b) presumed embolic basilar artery occlusions. Demographics, stroke
      characteristics, time metrics, recanalization results and outcome were recorded.
      Interventional strategies were evaluated concerning the thrombectomy technique,
      additional angioplasty, type of approach with respect to lesion pattern
      (ipsilateral to steno-occlusive VA lesion: dirty road or contralateral: clean
      road) and sequence of actions. RESULTS: Out of 157 patients treated for ABO 38
      (24.2%) had associated significant vertebrobasilar steno-occlusive lesions. An
      underlying significant basilar artery stenosis was present in 23.7% and
      additionally significant steno-occlusive vertebral lesions were present in 81.5%.
      Thrombectomy was performed with primary aspiration in 15.8% and with stent
      retrievers in 84.2%. Successful revascularization (TICI 2b-3) was achieved in
      86.8%. In 52.6% additional stent angioplasty was performed, in 7.9% balloon
      angioplasty only. The clean road approach was used in 22.5% of cases, the dirty
      road in 77.4%. Final modified Rankin scale (mRS) was 0-2 in 6 patients (15.8%)
      and 3-5 in 32 (84.2%). The in-hospital mortality was 36.8%. There were no
      statistically significant differences in outcome compared to presumed cases of
      embolisms. CONCLUSION: Endovascular treatment of ABO with underlying significant
      vertebrobasilar steno-occlusive lesions is effective and reasonably safe.
      Specific procedural strategies apply depending on individual patient pathology
      and anatomy. Although high rates of recanalization can be achieved, outcomes tend
      to be poor.

PMID- 29651588
TI  - Smoking Among Chinese Livery Drivers.
AB  - We aimed to assess a key risk factor for lung cancer, smoking, in a vulnerable
      group, Chinese livery drivers in New York City (NYC). This is a nested cohort
      study conducted in the summer/fall of 2014 within a larger NIMHD-funded R24
      program, the Taxi Network. The Taxi Network Needs Assessment (TNNA) survey was
      administered to a broad demographic of drivers. This study reports on the TNNA
      survey smoking-related results among NYC Chinese livery drivers. 97 drivers
      participated. Mean age was 44.7 years, 2.1% were English proficient, and 23.4%
      were living below the poverty line. Most were insured (82.5%), had a PCP (82.5%),
      and had had a routine check-up within the past year (79%). 73% were current or
      former smokers. Culturally and linguistically tailored smoking cessation
      interventions, strategies to mitigate exposure to air pollution, and programs to
      facilitate lung cancer screening should be developed and implemented for high
      risk Chinese livery drivers.

PMID- 29651589
TI  - Pre-migration Trauma, Repatriation Experiences, and PTSD Among North Korean
      Refugees.
AB  - Many studies on refugees suggested that refugees' traumatic events associated
      with post-traumatic stress disorder (PTSD). However, it is unknown whether
      refugees' PTSD was caused by their negative experience before or after the entry
      of their destination country. Thus, a separation of refugees' pre-migration from
      their post-migration experience is particularly important in understanding the
      causal impact of trauma. Using a sample from North Korean refugees, this study
      investigates the prevalence of PTSD symptoms, the impact of tortured trauma,
      repatriation experiences, on PTSD among North Korean refugees (n = 698). We found
      that North Korean refugees in our sample (a) demonstrated a high rate of current
      probable PTSD; (b) were demonstrated a higher frequency of repatriation
      experiences with a greater risk for PTSD symptoms. The findings suggest that
      particular types of trauma for populations with particular socio-demographic
      characteristics may be at a greater risk of PTSD.

PMID- 29651587
TI  - Isotope labeling for studying RNA by solid-state NMR spectroscopy.
AB  - Nucleic acids play key roles in most biological processes, either in isolation or
      in complex with proteins. Often they are difficult targets for structural
      studies, due to their dynamic behavior and high molecular weight. Solid-state
      nuclear magnetic resonance spectroscopy (ssNMR) provides a unique opportunity to
      study large biomolecules in a non-crystalline state at atomic resolution.
      Application of ssNMR to RNA, however, is still at an early stage of development
      and presents considerable challenges due to broad resonances and poor dispersion.
      Isotope labeling, either as nucleotide-specific, atom-specific or segmental
      labeling, can resolve resonance overlaps and reduce the line width, thus allowing
      ssNMR studies of RNA domains as part of large biomolecules or complexes. In this
      review we discuss the methods for RNA production and purification as well as
      numerous approaches for isotope labeling of RNA. Furthermore, we give a few
      examples that emphasize the instrumental role of isotope labeling and ssNMR for
      studying RNA as part of large ribonucleoprotein complexes.

PMID- 29651590
TI  - Effect of long-term acclimatization on summer thermal comfort in outdoor spaces:
      a comparative study between Melbourne and Hong Kong.
AB  - The Universal Thermal Climate Index (UTCI) is an index for assessing outdoor
      thermal environment which aims to be applicable universally to different
      climates. However, the scale of UTCI thermal stress classification can be
      interpreted depending on the context. Previous studies validated the UTCI in
      individual cities, but comparative studies between different cities are scarce.
      This study examines the differences in thermal perception and clothing choices
      between residents from two climate zones over similar UTCI ranges in summer. We
      compared summer thermal comfort survey data from Melbourne (n = 2162, January
      February 2014) and Hong Kong (n = 414, July-August 2007). We calculated the UTCI
      from outdoor weather station data and used t tests to compare the differences in
      thermal sensation and clothing between Hong Kong and Melbourne residents. When
      the UTCI was between 23.0 and 45.9  degrees C, Melbourne residents wore
      significantly more clothing (0.1 clo) than Hong Kong residents. Hong Kong
      residents reported neutral to warm sensation at a higher UTCI range compared with
      the dynamic thermal sensation (DTS) model. Moreover, Melbourne residents reported
      warm and hot sensation at a higher UTCI range than the DTS model. Respondents in
      Melbourne also exhibited different responses to the mean radiant temperature
      under shaded and sunny conditions, while such a trend was not observed in Hong
      Kong. It would be advisable to define different thermal sensation thresholds for
      the UTCI scale according to different climate zones for better prediction of the
      outdoor thermal comfort of different urban populations.

PMID- 29651591
TI  - Importance of QT/RR hysteresis correction in studies of drug-induced QTc interval
      changes.
AB  - QT/RR hysteresis and QT/RR adaptation are interlinked but separate physiological
      processes signifying how quickly and how much QT interval changes when heart rate
      changes, respectively. While QT interval duration is, as a rule, corrected for
      heart rate in terms of the QT/RR adaptation, the correction for QT/RR hysteresis
      is frequently omitted in studies of drug-induced QTc changes. This study used
      data from previously conducted thorough QT studies to investigate the extent of
      QTc errors caused by omitting the correction for QT/RR hysteresis, particularly
      in small clinical investigations. Statistical modeling approach was used to
      generate 11,000 simulated samples of 10-subject studies in which mixed effect
      PK/PD models were used to estimate drug-induced QTc changes at mean maximum
      plasma concentration of investigated compounds. Calculations of QTc intervals
      involving and omitting QT/RR hysteresis correction were compared. These
      comparisons showed that ignoring QT/RR hysteresis has two undesirable effects:
      (A) In the design of subject-specific heart rate corrections (needed in studies
      of drugs that change heart rate) omission of QT/RR hysteresis may lead to signals
      of QTc prolongation of more than 10 ms to be missed. (B) Irrespective of whether
      the investigated drug changes heart rate, omission of QT/RR hysteresis causes the
      widths of the confidence intervals of the PK/PD predicted QTc interval changes to
      be increased by 20-30% on average (exceeding 50% in some cases). This may lead to
      a failure of excluding meaningful QTc prolongation which would be excluded if
      using hysteresis correction. The study concludes that correction for QT/RR
      hysteresis should be incorporated into future studies of drug-induced QTc
      changes. Subject-specific heart rate corrections that omit hysteresis correction
      may lead to erroneously biased conclusions. Even when using universal (e.g.
      Fridericia) heart rate correction, hysteresis correction decreases the confidence
      intervals of QTc changes and thus helps avoiding false positive outcomes.

PMID- 29651592
TI  - Influence of Zn, Cd, and Cu fractions on enzymatic activity of arable soils.
AB  - The aim of this study was to investigate the heavy metal effect on enzymatic
      activity in acidic soil samples during spring, summer, and autumn. The four metal
      fractions, acid-soluble and exchangeable (F1), reducible (F2), oxidizable (F3),
      and residual (F4) using BCR method in soil samples, were evaluated. The highest
      percentage share of zinc and copper was determined in F4 (45.8, 54.9%,
      respectively) and cadmium in F3 (45.6%). The enzymatic activity in soil was
      differentiated in seasons. During spring, the significant relationship was noted
      between F1/zinc/dehydrogenase, during summer F2/cadmium/phosphatase as well as
      F4/cadmium/dehydrogenase and autumn F3/zinc/dehydrogenase. Fraction
      F1/zinc/copper influenced phosphatase activity, whereas F3/Zn increased
      dehydrogenase and F2/Cd protease activity. The results indicate that the heavy
      metals affected dehydrogenase activity the most.

PMID- 29651593
TI  - Cervical pedicle screw instrumentation is more reliable with O-arm-based 3D
      navigation: analysis of cervical pedicle screw placement accuracy with O-arm
      based 3D navigation.
AB  - PURPOSE: Despite proven biomechanical superiority and resultant superior clinical
      outcomes, pedicle instrumentation in cervical spine is not widely practiced due
      to technical difficulties, steep learning curve, and possible potential
      catastrophic complications due to screw misplacement. This study was undertaken
      with the purpose to evaluate the feasibility, accuracy, and complications of
      cervical pedicle screw instrumentation solely using O-arm-based 3D navigation
      technology. METHODS: Prospectively maintained data from a single-surgeon case
      series were retrospectively analyzed. All the patients had undergone cervical
      pedicle instrumentation under O-arm 3D navigation. Screw placement accuracy was
      analyzed and compared among different vertebral levels and also between different
      patient groups. RESULTS: A total of 241 cervical pedicle screws were inserted in
      44 patients. Out of the 241 screws, 197 (81.74%) were inserted at the level of C3
      C6 vertebrae with nearly equal distribution among the 4 vertebrae, followed by 32
      (13.28%) and 12 (4.98%) screws at C2 and C7 vertebrae, respectively. After the
      analysis of screw placement as per Gertzbein classification, the overall breach
      rates were found to be 7.05% (17 screws) with 52.94% (10 screws) Grade I, 47.06%
      (7 screws) Grade II, and nil Grade III screw breaches. CONCLUSION: The use of O
      arm-based intra-operative 3D scans for navigation can make cervical pedicle screw
      placement reliable. High accuracy and better intra-operative control can increase
      surgeon's confidence in using cervical pedicle instrumentation on more regular
      basis. These slides can be retrieved under Electronic Supplementary Material.

PMID- 29651594
TI  - Prospective study of shoulder strength, shoulder range of motion, and lymphedema
      in breast cancer patients from pre-surgery to 5 years after ALND or SLNB.
AB  - OBJECTIVE: Determine the changes in shoulder strength, shoulder range of motion,
      and arm volume in breast cancer patients treated with sentinel lymph node biopsy
      (SLNB) or axillary lymph node dissection (ALND) METHOD: Sixty-eight SLNB and 44
      ALND patients were followed up from pre-surgery to 5 years after surgery. Primary
      outcomes were the differences between affected and non-affected sides for the
      following: shoulder strength measured by dynamometry, shoulder range of motion
      measured by goniometry, and lymphedema measured by volume. As a secondary
      outcome, health-related quality of life (HRQL) was assessed by the Short Form-36
      Health Survey (SF-36) and the Functional Assessment of Cancer Therapy for breast
      cancer (FACT-B+4) questionnaires. Changes over time were tested for SLNB and ALND
      using univariate repeated measures analysis of variance. Generalized estimating
      equation models were constructed to assess the effect of SLNB and ALND over time.
      RESULTS: After 5 years, the ALND group had significant loss of strength for
      internal rotators (1.39 kg, p = 0.001) and significant arm volume increase
      (132.45 mL, p = 0.031). The ALND group had a greater number of patients with
      clinically relevant internal rotator strength loss (38.7 vs. 13.6%, p = 0.012)
      and a greater number of lymphedema requiring treatment (33.3 vs. 3.4%, p < 0.001)
      than the SLNB group. A loss of strength for shoulder external rotators, shoulder
      range of motion, and HRQL in physical and arm domains persisted at 5 years in
      both SLNB and ALND groups. CONCLUSION: These results could help understand and
      plan the prevention, needs, and long-term care of breast cancer patients.

PMID- 29651595
TI  - Heart rate variability for rapid risk stratification of emergency patients with
      malignant disease.
AB  - INTRODUCTION: Neoplasms are the second most common diseases in western countries.
      Many patients with malignant diseases repeatedly present themselves in the
      emergency department (ED). Due to limited capacities, appropriate risk
      stratification strategies for cancer patients have to be developed. This study
      assesses if deceleration capacity (DC) of heart rate as a parameter of heart rate
      variability predicts mortality in emergency patients with malignant diseases.
      METHODS: Prospectively, 140 adults with different entities of malignant diseases
      who presented in the medical ED were included. Primary and secondary endpoints
      were intrahospital mortality and mortality within 180 days, respectively. We
      calculated DC from short-term ECG readings of the surveillance monitors.
      Additionally, the Modified Early Warning Score (MEWS) and laboratory parameters
      such as white blood cells (WBC), lactate dehydrogenase, serum hemoglobin, and
      serum creatinine were determined. RESULTS: The median age of the patients was 65
      +/- 14 years. 19.3% of the patients died within the hospital stay and 57.9% died
      within 180 days. DC and WBC were independent predictors of intrahospital death
      reaching a hazard ratio (HR) of 0.79 (95% confidence interval (CI) 0.63-0.993, p
      = 0.043) and of 1.00 (95% CI 1.00-1.00, p = 0.003), respectively. DC and serum
      creatinine independently predicted death within 180 days (HR 0.90, 95% CI 0.82
      0.98, p = 0.023 and HR 1.41, 95% CI 1.05-1.90, p = 0.018, respectively).
      CONCLUSION: Deceleration capacity of heart rate is suitable for rapid risk
      assessment of emergency patients with malignant diseases.

PMID- 29651596
TI  - Predictors of attendance to an oncologist-referred exercise program for women
      with breast cancer.
AB  - PURPOSE: While exercise is associated with numerous benefits in women with breast
      cancer, adherence to exercise training concurrent to cancer treatment is
      challenging. We aimed to identify predictors of attendance to an oncologist
      referred exercise program offered during and after adjuvant breast cancer
      treatment. METHODS: Women with early-stage breast cancer receiving chemotherapy
      (n = 68) enrolled in the Nutrition and Exercise During Adjuvant Treatment (NExT)
      study. Supervised aerobic and resistance exercise was prescribed three times per
      week during treatment, then one to two times per week for 20 additional weeks.
      Predictors of attendance were identified using multivariate linear regression for
      three phases of the intervention, including during (1) adjuvant chemotherapy, (2)
      radiation, and (3) 20-weeks post-treatment. RESULTS: Higher baseline quality of
      life (QoL) predicted higher attendance during chemotherapy (beta = 0.51%, 95 CI:
      0.09, 0.93) and radiation (beta = 0.85%, 95 CI: 0.28, 1.41), and higher QoL,
      measured at the end of treatment, predicted higher attendance post-treatment
      (beta = 0.81%, 95 CI: 0.34, 1.28). Being employed pre-treatment (beta = 34.08%,
      95 CI: 5.71, 62.45) and a personal annual income > $80,000 (beta = 32.70%, 95 CI:
      0.85, 64.55) predicted higher attendance during radiation. Being divorced,
      separated or widowed (beta = - 34.62%, 95 CI: - 56.33, - 12.90), or single (beta
      = - 25.38%, 95 CI: - 40.64, - 10.13), relative to being married/common-law, and
      undergoing a second surgery (beta = - 21.37%, 95 CI: - 33.10, - 9.65) predicted
      lower attendance post-treatment. CONCLUSIONS: Demographic variables, QoL, and
      receipt of a second surgery significantly predicted attendance throughout the
      NExT supervised exercise program. These results may help identify individuals
      with exercise adherence challenges and improve the design of future
      interventions, including optimizing the timing of program delivery.

PMID- 29651597
TI  - A two-dimensional model of disrupted body integrity: initial evaluation in head
      and neck cancer.
AB  - PURPOSE: This cross-sectional study presents an initial psychometric evaluation
      of a two-dimensional (perceptual and evaluative) conceptualization and measure of
      disrupted body integrity (DBI)-illness-related disruption of the sense of the
      body as an integrated, smoothly functioning whole. METHODS: Male and female head
      and neck cancer (HNC) outpatients (N = 98) completed a questionnaire package
      prior to outpatient visits. MAIN OUTCOME MEASURES: The Disrupted Body Integrity
      Scale (DBIS) was developed to measure the perceptual and evaluative facets of
      DBI. Self-report measures of disfigurement, stigma, depressive symptoms, and
      negative affect were also completed. RESULTS: Almost all DBIS subscales
      demonstrated good internal consistency. Results largely supported the DBIS's
      construct validity. The majority of subscales correlated within the predicted
      range of r's = .40-.70. Almost all DBIS constructs were positively linked with
      either depressive symptoms or disfigurement. None correlated with positive
      affect, and only two subscales, abnormal sensations (perceptual) and physical
      vulnerability (evaluative), correlated with negative affect. DBIS constructs
      showed little relation with stigma, once disfigurement effects were controlled
      for. CONCLUSIONS: Findings offer preliminary evidence for the DBIS and the
      relevance of DBI in HNC. Further evaluation of DBI in disease adaptation and the
      DBIS's factor structure is warranted.

PMID- 29651598
TI  - Geriatric Assessment for Older Patients with Non-small Cell Lung Cancer: Daily
      Practice of Centers Participating in the NVALT25-ELDAPT Trial.
AB  - INTRODUCTION: Geriatric assessment (GA) for older patients with lung cancer could
      provide insight into vulnerability, cognitive impairment, and risk of toxicity.
      Discontinuation and complications of intensive treatment could potentially be
      prevented in vulnerable and frail patients. This study aimed to evaluate current
      clinical practice of GA for older patients with lung cancer in the Netherlands
      and identify potential hurdles for implementation. METHODS: Pulmonologists and
      radiation oncologists participating in the NVALT25-ELDAPT trial completed an
      online questionnaire regarding current practice of GA, added value of GA for
      treatment decision-making and logistic barriers for patients with non-small cell
      lung cancer. RESULTS: 15 out of 17 centers responded. Three performed GA as
      standard procedure, three on indication, eight considered a frailty screening
      step before GA, and one did not perform GA. Suspicion of cognitive problems was
      mentioned most often as indication for GA and of added value for treatment
      decision-making, followed by older age, curative-intent treatment, and stage I
      III lung cancer. Administered instruments for screening and extensive GA were
      diverse. Main barriers to implement GA in clinical practice were logistic
      problems (timescales and availability of trained personnel). CONCLUSION: The use
      of GA in clinical practice for patients with lung cancer varied widely across
      centers regarding instruments and domains. Physicians are uniform in their
      opinion about indications for GA and the added value for treatment decision
      making. Research should focus on manageable instruments and important domains to
      assess for this heterogeneous group of older patients with lung cancer to
      optimize treatment selection. Trial registration The NVALT25-ELDAPT trial is
      registered under trial number NCT02284308. Details are available at
      http://www.eldapt.org (predominantly in Dutch).

PMID- 29651599
TI  - [Spirituality in old age as dynamic aging task].
AB  - BACKGROUND: A multitude of studies have demonstrated a positive effect of
      spirituality for dealing with difficult situations in life; however, specific
      studies on spirituality in older age are exceptionally rare within the German
      gerontological research landscape. The theory of gerotranscendence by Tornstam
      indicates that spirituality is of particular importance for maintaining life
      satisfaction especially in older age, due to a change in perspective. OBJECTIVES:
      This study looked into the research questions of how spirituality is presented in
      the oldest old (80 years and older) in Germany and to what extent its
      characteristics are specific to older age. MATERIAL AND METHODS: Problem-centered
      interviews were conducted with 20 oldest old subjects and evaluated using
      qualitative content analysis. RESULTS: Spirituality in itself is not specific to
      very old age. Its shaping, however, as an existential process of transformation
      and redefinition, is specific in the oldest old due to their socialization and
      biographical experiences over the life course impregnated by processes of
      subjectification and individualization. In addition, its relation to existential
      questions gains increasing relevance and priority in very old age in an
      affective, reflective and performative dimension, and the answers change between
      fragility and continuity. CONCLUSION: As a heterogeneous (intermediate) result of
      experiences over the life course against the background of socialization and
      individual existential interpretation of "Self" and "World", spirituality in the
      oldest old should be perceived in this diverse and dynamic manner in research and
      practice, in order to foster well-being in old age.

PMID- 29651601
TI  - Predictors of Labor Force Status in a Random Sample of Consumers with Serious
      Mental Illness.
AB  - Employment among persons with severe mental illness has been challenging.
      Supported employment programs have had some success; however, much remains to be
      understood about client motivations for employment. A labor force participation
      study was mailed to persons receiving services in a Midwestern state's publicly
      funded behavioral health system, and a random sample of participants resulted in
      964 valid surveys. Analysis showed significant differences between Medicaid
      coverage program and labor force status, with some programs likely to have higher
      percentages of employed persons. A multinomial logistic regression model explored
      the odds of employment and unemployment to not being in the labor force.
      Perception of incentives to employment greatly increased the odds, while age and
      perception of barriers to employment decreased the odds for both groups when
      compared to those not in the labor force. Findings have implications for the
      design of employment programs and coverage benefits.

PMID- 29651600
TI  - Measuring Quality of Care in Community Mental Health: Validation of Concordant
      Clinician and Client Quality-of-Care Scales.
AB  - Measuring quality of care can transform care, but few tools exist to measure
      quality from the client's perspective. The aim of this study was to create
      concordant clinician and client self-report quality-of-care scales in a sample of
      community mental health clinicians (n = 189) and clients (n = 469). The client
      scale had three distinct factors (Person-Centered Care, Negative Staff
      Interactions, and Inattentive Care), while the clinician scale had two: Person
      Centered Care and Discordant Care. Both versions demonstrated adequate internal
      consistency and validity with measures related to satisfaction and the
      therapeutic relationship. These measures are promising, brief quality assessment
      tools.

PMID- 29651602
TI  - Cry of a dying kidney: Questions.

PMID- 29651603
TI  - Cry of a dying kidney: Answers.

PMID- 29651604
TI  - Patterns and frequency of renal abnormalities in Fanconi anaemia: implications
      for long-term management.
AB  - BACKGROUND: Fanconi anaemia (FA) is an inherited disease with bone marrow
      failure, variable congenital and developmental abnormalities, and cancer
      predisposition. With improved survival, non-haematological manifestations of FA
      become increasingly important for long-term management. While renal abnormalities
      are recognized, detailed data on patterns and frequency and implications for long
      term management are sparse. METHODS: We reviewed clinical course and imaging
      findings of FA patients with respect to renal complications in our centre over a
      25-year period to formulate some practical suggestions for guidelines for
      management of renal problems associated with FA. RESULTS: Thirty patients
      including four sibling sets were reviewed. On imaging, 14 had evidence of
      anatomical abnormalities of the kidneys. Two cases with severe phenotype,
      including renal abnormalities, had chronic kidney disease (CKD) at diagnosis.
      Haematopoietic stem cell transplantation was complicated by significant acute
      kidney injury (AKI) in three cases. In three patients, there was CKD at long-term
      follow-up. All patients had normal blood pressure. CONCLUSIONS: Evaluation of
      renal anatomy with ultrasound imaging is important at diagnostic workup of FA.
      While CKD is uncommon at diagnosis, our data suggests that the incidence of CKD
      increases with age, in particular after haematopoietic stem cell transplantation.
      Monitoring of renal function is essential for management of FA. Based on these
      long-term clinical observations, we formulate some practical guidelines for
      assessment and management of renal abnormalities in FA.

PMID- 29651605
TI  - Diagnostic role of strain imaging in atypical myocarditis by echocardiography and
      cardiac MRI.
AB  - BACKGROUND: The diagnosis of myocarditis presenting as isolated acute chest pain
      with elevated troponins but normal systolic function is challenging with
      significant drawbacks even for the gold-standard endomyocardial biopsy.
      OBJECTIVE: This study aimed to evaluate the diagnostic role of strain imaging by
      echocardiography and cardiac MRI in these patients. MATERIALS AND METHODS: This
      was a retrospective review of children with cardiac MRI for acute chest pain with
      elevated troponins compared to normal controls. Echocardiographic fractional
      shortening, ejection fraction, speckle-tracking-derived peak longitudinal,
      radial, and circumferential strain were compared to cardiac MRI ejection
      fraction, T2 imaging, late gadolinium enhancement, speckle-tracking-derived peak
      longitudinal strain, radial strain, and circumferential strain. RESULTS: Group 1
      included 10 subjects diagnosed with myocarditis, 9 (90%) males with a median age
      of 15.5 years (range: 14-17 years) compared with 10 age-matched controls in group
      2. All subjects in group 1 had late gadolinium enhancement consistent with
      myocarditis and troponin ranged from 2.5 to >30 ng/ml. Electrocardiogram changes
      included ST segment elevation in 6 and abnormal Q waves in 1. Qualitative
      echocardiographic function was normal in both groups and mean fractional
      shortening was similar (35+/-6% in group 1 vs. 34+/-4% in group 2, P=0.70). Left
      ventricle ejection fraction by cardiac MRI, however, was lower in group 1 (52+/
      9%) compared to group 2 at (59+/-4%) (P=0.03). Cardiac MRI derived strain was
      lower in group 1 vs. group 2 for speckle-tracking-derived peak longitudinal
      strain (-12.8+/-2.8% vs. -17.1+/-1.5%, P=0.001), circumferential strain (-12.3+/
      3.8% vs. -15.8+/-1.2%, P=0.020) and radial strain (13.6+/-3.7% vs. 17.2+/-3.2%,
      P=0.040). Echocardiography derived strain was also lower in group 1 vs. group 2
      for speckle-tracking-derived peak longitudinal strain (-15.6+/-3.9% vs. -20.8+/
      2.2%, P<0.002), circumferential strain (-16+/-3% vs. -19.8+/-1.9%, P<0.003) and
      radial strain (17.3+/-6.1% vs. 24.8+/-6.3%, P=0.010). CONCLUSION: In previously
      asymptomatic children, myocarditis can present with symptoms of acute chest pain
      suspicious for coronary ischemia. Cardiac MRI and echocardiographic strain
      imaging are noninvasive, radiation-free tests of immense diagnostic utility in
      these situations. Long-term studies are needed to assess prognostic significance
      of these findings.

PMID- 29651606
TI  - Age-related apparent diffusion coefficients of lumbar vertebrae in healthy
      children at 1.5 T.
AB  - BACKGROUND: Diffusion-weighted magnetic resonance imaging with apparent diffusion
      coefficient (ADC) calculation is important for detecting bone marrow pathologies.
      OBJECTIVE: To investigate age-related differences of lumbar vertebral body ADC to
      establish normal values for healthy children. MATERIALS AND METHODS: Forty-nine
      healthy children without any history of oncological or hematological diseases
      (10.2+/-4.7 years, range: 0-20 years) were included in this retrospective study.
      All magnetic resonance imaging (MRI) examinations were performed at 1.5 T and
      with similar scan parameters. The diffusion-weighted sequences were performed
      with b values of 50, 400 and 800 s/mm2. ADC values were measured by placing
      regions of interest at three different levels within each lumbar vertebral body
      (L1 to L5). ADC values were analyzed for different age groups (0-2 years, 3-6
      years, 7-11 years, 12-14 years, 15-20 years), for each vertebral and
      intravertebral level. RESULTS: The mean ADC of the whole study group was 0.60+/
      0.09 * 10-3 mm2/s. Children between the ages of 12 and 14 years had significantly
      higher ADC compared to the other age groups (P<=0.0003). ADC values were
      significantly higher in the 1st lumbar vertebral body compared to the other
      levels of the lumbar spine (P<0.005) with the exception of L5, and in the upper
      third of the vertebral bodies compared to the middle or lower thirds (P<=0.003).
      CONCLUSION: The age-, vertebral- and intravertebral level-dependent differences
      in ADC suggest a varying composition and cellularity in different age groups and
      in different locations.

PMID- 29651607
TI  - Detecting inflammation in inflammatory bowel disease - how does ultrasound
      compare to magnetic resonance enterography using standardised scoring systems?
AB  - BACKGROUND: Magnetic resonance enterography (MRE) is the current gold standard
      for imaging in inflammatory bowel disease, but ultrasound (US) is a potential
      alternative. OBJECTIVE: To determine whether US is as good as MRE for the
      detecting inflamed bowel, using a combined consensus score as the reference
      standard. MATERIALS AND METHODS: We conducted a retrospective cohort study in
      children and adolescents <18 years with inflammatory bowel disease (IBD) at a
      tertiary and quaternary centre. We included children who underwent MRE and US
      within 4 weeks. We scored MRE using the London score and US using a score adapted
      from the METRIC (MR Enterography or Ultrasound in Crohn's Disease) trial. Four
      gastroenterologists assessed an independent clinical consensus score. A combined
      consensus score using the imaging and clinical scores was agreed upon and used as
      the reference standard to compare MRE with US. RESULTS: We included 53 children.
      At a whole-patient level, MRE scores were 2% higher than US scores. We used Lin
      coefficient to assess inter-observer variability. The repeatability of MRE scores
      was poor (Lin 0.6). Agreement for US scoring was substantial (Lin 0.95). There
      was a significant positive correlation between MRE and clinical consensus scores
      (Spearman's rho = 0.598, P=0.0053) and US and clinical consensus scores
      (Spearman's rho = 0.657, P=0.0016). CONCLUSION: US detects as much clinically
      significant bowel disease as MRE. It is possible that MRE overestimates the
      presence of disease when using a scoring system. This study demonstrates the
      feasibility of using a clinical consensus reference standard in paediatric IBD
      imaging studies.

PMID- 29651608
TI  - On Fair Person Classification Based on Efficient Factor Score Estimates in the
      Multidimensional Factor Analysis Model.
AB  - Since Hooker, Finkelman and Schwartzman (Psychometrika 74(3): 419-442, 2009) it
      is known that person parameter estimates from multidimensional latent variable
      models can induce unfair classifications via paradoxical scoring effects. The
      open question as to whether there is a fair and at the same time multidimensional
      scoring scheme with adequate statistical properties is addressed in this paper.
      We develop a theorem on the existence of a fair, multidimensional classification
      scheme in the context of the classical linear factor analysis model and show how
      the computation of the scoring scheme can be embedded in the context of linear
      programming. The procedure is illustrated in the framework of scoring the
      Wechsler Adult Intelligence Scale (WAIS-IV).

PMID- 29651609
TI  - The Delta Opioid Peptide DADLE Represses Hypoxia-Reperfusion Mimicked Stress
      Mediated Apoptotic Cell Death in Human Mesenchymal Stem Cells in Part by
      Downregulating the Unfolded Protein Response and ROS along with Enhanced Anti
      Inflammatory Effect.
AB  - Hypoxia-reperfusion (H/R) emblems a plethora of pathological conditions which is
      potent in contributing to the adversities encountered by human mesenchymal stem
      cells (hMSCs) in post-transplant microenvironment, resulting in transplant
      failure. D-Alanine 2, Leucine 5 Enkephaline (DADLE)-mediated delta opioid
      receptor (DOR) activation is well-known for its recuperative properties in
      different cell types like neuronal and cardiomyocytes. In the current study its
      effectiveness in assuaging hMSC mortality under H/R-like insult has been
      delineated. The CoCl2 mimicked H/R conditions in vitro was investigated upon DOR
      activation, mediated via DADLE. hMSCs loss of viability, reactive oxygen species
      (ROS) production, inflammatory responses and disconcerted unfolded protein
      response (UPR) were assessed using AnnexinV/PI flow cytometry, fluorescence
      imaging, mitochondrial complex 1 assay, quantitative PCR, immunoblot analysis and
      ELISA. H/R like stress induced apoptosis of hMSCs was significantly mitigated by
      DADLE via modulation of the apoptotic regulators (Bcl-2/Bax) along with
      significant curtailment of ROS and mitochondrial complex 1 activity. DADLE
      concomitantly repressed the misfolded protein aggregation, alongside the major
      UPR sensors: PERK/BiP/IRE-1alpha /ATF-6, evoked due to the H/R mimicked
      endoplasmic reticulum stress. Undermined phosphorylation of the Akt signalling
      pathway was observed, which concerted its effect onto regulating both the pro and
      anti-inflammatory cytokines, actuated as a response to the H/R-like insult. The
      effects of DADLE were subdued by naltrindole (specific DOR antagonist)
      reaffirming the involvement of DOR in the process. Taken together these results
      promulgate the role of DADLE-induced DOR activation on improved hMSC survival,
      which signifies the plausible implications of DOR-activation in cell
      transplantation therapies and tissue engineering aspect.

PMID- 29651610
TI  - Periprosthetic femoral fracture as cause of early revision after short stem hip
      arthroplasty-a multicentric analysis.
AB  - BACKGROUND: The objective of this study was to analyze the prevalence and causes
      of early re-operation after hip replacement surgery using short bone-preserving
      stems in a large multicentre series. Specifically, we evaluated the clinical
      features of periprosthetic fractures occurring around short stems. METHODS: A
      total of 897 patients (1089 hips) who underwent primary total hip arthroplasty or
      bipolar hemiarthroplasty from January 2011 to February 2015 using short bone
      preserving femoral stems were recruited. Mean patient age was 57.4 years (range,
      18-97 years), with a male ratio of 49.7% (541/1089). Re-operation for any reason
      within two years was used as an endpoint. The incidence and clinical
      characteristics of the periprosthetic femoral fractures were also recorded. Mean
      follow-up period was 5.1 years (range, 2-7.9 years). RESULTS: Early re-operation
      for any reason was identified in 16 (1.5%) of 1089 hips. The main reason for re
      operation was periprosthetic femoral fracture, which accounted for eight (50%) of
      the 16 re-operations. The overall incidence of periprosthetic femoral fracture at
      two years was 1.1% (12/1089). According to the Vancouver classification, two
      fractures were AG type and the other ten were B1 type. Advanced age, higher
      American Society of Anesthesiologist grade, femur morphology of Dorr type C, and
      the use of a calcar-loading stem increased the risk for periprosthetic femoral
      fracture. CONCLUSION: Periprosthetic femoral fracture was the major reason for re
      operation after hip replacement surgery using short bone-preserving stems
      accounting for 50% (8/16) of re-operations two years post-operatively, but did
      not seem to deteriorate survivorship of implanted prostheses.

PMID- 29651612
TI  - ?

PMID- 29651611
TI  - Risk factors for medical complications after long-level internal fixation in the
      treatment of adult degenerative scoliosis.
AB  - PURPOSE: This study evaluates baseline patient characteristics and surgical
      parameters for risk factors of medical complications in ASD patients received
      posterior long level internal fixation. METHODS: Analysis of consecutive patients
      who underwent posterior long-level instruction fixation for adult degenerative
      scoliosis (ADS) with a minimum of two year follow-up was performed. Pre-operative
      risk factors, intraoperative variables, peri-operative radiographic parameters,
      and surgical-related risk factors were collected to analyze the effect of risk
      factors on medical complications. Patients were separated into groups with and
      without medical complication. Then, complication group was further classified as
      major or minor medical complications. Potential risk factors were identified by
      univariate testing. Multivariate logistic regression was used to evaluate
      independent predictors of medical complications. RESULTS: One hundred and thirty
      one ADS patients who underwent posterior long segment pedicle screws fixation
      were included. Total medical complication incidence was 25.2%, which included
      infection (12.2%), neurological (11.5%), cardiopulmonary (7.6%), gastrointestinal
      (6.1%), and renal (1.5%) complications. Overall, 7.6% of patients developed major
      medical complications, and 17.6% of patients developed minor medical
      complications. The radiographic parameters of pre-operative and last follow-up
      had no significant difference between the groups of medical complications and the
      major or minor medical complications subgroups. However, the incidence of
      cerebrospinal fluid leak (CFL) in patients who without medical complications was
      much lower than that with medical complications (18.4 vs. 42.4%, P = 0.005).
      Independent risk factors for development of medical complications included
      smoking (OR = 6.45, P = 0.012), heart disease (OR = 10.07, P = 0.012), fusion
      level (OR = 2.12, P = 0.001), and length of hospital stay (LOS) (OR = 2.11, P =
      0.000). Independent risk factors for development of major medical complications
      were diabetes (OR 6.81, P = 0.047) and heart disease (OR = 5.99, P = 0.049).
      Except for the last follow-up, Oswestry Disability Index and visual analog scale
      of the patient experienced medical complications trend higher score; the clinical
      outcomes have no significant difference between the medical and major
      complications groups. CONCLUSION: Heart disease comorbidity is an independent
      risk factor for both medical and major medical complications. Smoking, fusion
      level, and LOS are independent risk factors for medical complication. Diabetes is
      the independent risk factors for major medical complications.

PMID- 29651613
TI  - ?

PMID- 29651614
TI  - Antibiotics for recurrent acute pharyngo-tonsillitis: systematic review.
AB  - The purpose was to determine the current evidence for preferable antibiotic
      treatment in three common clinical situations with insufficient consensus: Q1:
      Can antibiotic treatment prevent future attacks of acute pharyngo-tonsillitis
      (APT) in patients with recurrent APT (RAPT)? Q2: Which antibiotic regimen is
      preferable in the treatment of APT in patients with RAPT? Q3: Which antibiotic
      regimen is preferable in the treatment of relapsing APT? Five databases were
      searched systematically for randomized clinical trials on patients with RAPT with
      or without current APT or with relapse of APT. Of the unique publications, 643
      were found. Five studies addressing Q1 (n = 3) and Q2 (n = 2) met the eligibility
      criteria. No studies reporting on Q3 were included. Q1: Two studies found that
      clindamycin and cefpodoxime, respectively, were effective in preventing future
      APT episodes and in eradicating group A streptococci from the tonsils of RAPT
      patients. One study found that long-term azithromycin had no effect on the number
      of APT episodes. Q2: Two studies reported superior clinical and microbiological
      effects of clindamycin and amoxicillin with clavulanate, respectively, compared
      to penicillin. The four studies showing superior effects of clindamycin and
      amoxicillin with clavulanate were assessed to have high risk of bias. Hence, the
      level of evidence was moderate. There is considerable evidence to suggest that
      clindamycin and amoxicillin with clavulanate are superior to penicillin with
      preferable effects on the microbiological flora and the number of future attacks
      of APT in patients with RAPT. Antibiotic treatment is an option in patients with
      RAPT, who has contraindications for tonsillectomy.

PMID- 29651615
TI  - Usefulness of Sofia Pneumococcal FIA(r) test in comparison with BinaxNOW(r)
      Pneumococcal test in urine samples for the diagnosis of pneumococcal pneumonia.
AB  - The Sofia Pneumococcal FIA(r) test is a recently introduced immunofluorescent
      assay automatically read aimed to detect Streptococcus pneumoniae antigen in
      urine. The aim of this study was to evaluate the usefulness of SofiaFIA(r)
      urinary antigen test (UAT) in comparison with classical immunochromatographic
      BinaxNOW(r) test for the diagnosis of pneumococcal pneumonia (PP). Observational
      study was conducted in the Hospital Universitari Vall d'Hebron from December 2015
      to August 2016. Consecutive adult patients diagnosed of pneumonia and admitted to
      the emergency department in whom UAT was requested were prospectively enrolled.
      Paired pneumococcal UAT was performed (BinaxNOW(r) and SofiaFIA(r)) in urine
      samples. To assess the performance of both tests, patients were categorized into
      proven PP (isolation of S. pneumoniae in sterile fluid) or probable PP (isolation
      of S. pneumoniae in respiratory secretion). Sensitivity, specificity, and
      concordance were calculated. A total of 219 patients with pneumonia were
      enrolled, of whom 14% had a proven or probable PP, 22% a non-pneumococcal
      etiology, and 64% an unidentified pathogen. Concordance between tests was good
      (kappa = 0.81). Sensitivity of SofiaFIA(r) and BinaxNOW(r) UAT was 78.6 and 50%
      for proven PP (p = 0.124), and 74.2 and 58% for proven/probable PP (p = 0.063).
      Specificity for both tests was 83.3 and 85.5% for proven and proven/probable PP.
      In patients without an identified pathogen, SofiaFIA(r) test was positive in 33
      (23.6%) cases and BinaxNOW(r) in 25 (17.8%), so Sofia Pneumococcal FIA(r)
      detected 32.6% more cases than BinaxNOW(r) (p = 0.001). Sofia Pneumococcal FIA(r)
      test showed an improved sensitivity over visual reading of BinaxNOW(r) test
      without a noticeable loss of specificity.

PMID- 29651616
TI  - Significant increase in cultivation of Gardnerella vaginalis, Alloscardovia
      omnicolens, Actinotignum schaalii, and Actinomyces spp. in urine samples with
      total laboratory automation.
AB  - While total laboratory automation (TLA) is well established in laboratory
      medicine, only a few microbiological laboratories are using TLA systems.
      Especially in terms of speed and accuracy, working with TLA is expected to be
      superior to conventional microbiology. We compared in total 35,564
      microbiological urine cultures with and without incubation and processing with BD
      Kiestra TLA for a 6-month period each retrospectively. Sixteen thousand three
      hundred thirty-eight urine samples were analyzed in the pre-TLA period and 19,226
      with TLA. Sixty-two percent (n = 10,101/16338) of the cultures processed without
      TLA and 68% (n = 13,102/19226) of the cultures processed with TLA showed growth.
      There were significantly more samples with two or more species per sample and
      with low numbers of colony forming units (CFU) after incubation with TLA.
      Regarding the type of bacteria, there were comparable amounts of
      Enterobacteriaceae in the samples, slightly less non-fermenting Gram-negative
      bacteria, but significantly more Gram-positive cocci, and Gram-positive rods.
      Especially Alloscardivia omnicolens, Gardnerella vaginalis, Actinomyces spp., and
      Actinotignum schaalii were significantly more abundant in the samples incubated
      and processed with TLA. The time to report was significantly lower in the TLA
      processed samples by 1.5 h. We provide the first report in Europe of a large
      number of urine samples processed with TLA. TLA showed enhanced growth of non
      classical and rarely cultured bacteria from urine samples. Our findings suggest
      that previously underestimated bacteria may be relevant pathogens for urinary
      tract infections. Further studies are needed to confirm our findings.

PMID- 29651617
TI  - Delayed vs. immediate stenting in STEMI with a high thrombus burden : A
      systematic review and meta-analysis.
AB  - BACKGROUND: The results of several large-scale randomized controlled trials are
      controversial regarding the advantages of delayed stenting (DS) compared with
      immediate stenting (IS). We sought to determine whether DS has benefits for
      patients with ST-segment elevation myocardial infarction (STEMI) with a high
      thrombus burden compared with IS. METHODS: We systematically searched four
      electronic databases. Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow,
      TIMI myocardial blush grade (TMBG), complete ST-segment resolution (>70%), major
      adverse cardiac events (MACE), and major bleeding complications were studied as
      outcomes. Data analysis was performed using a random-effects model utilizing the
      Review Manager 5.3 software. RESULTS: Our meta-analysis included eight studies
      involving 744 patients. DS showed greater benefits than IS in terms of TIMI grade
      3 flow (odds ratio [OR]: 5.09, 95% confidence interval [CI]: 1.98-13.02, p <
      0.001), TMBG (OR: 4.17, 95% CI: 1.87-9.31, p < 0.001), complete ST-segment
      resolution (OR: 2.16, 95% CI: 1.36-3.43, p = 0.001), and MACE (OR: 0.48, 95% CI:
      0.25-0.94, p = 0.03). No significant difference was observed regarding major
      bleeding events (OR: 1.76, 95% CI: 0.40-7.66, p = 0.45). CONCLUSION: DS yielded
      satisfactory outcomes regarding myocardial tissue reperfusion, demonstrated by
      the improved TIMI flow grade, TMBG, complete ST-segment resolution, and decreased
      MACEs without increasing major bleeding events in patients with STEMI and a high
      thrombus burden. DS may be preferred to IS for treating patients with this
      characteristic presentation.

PMID- 29651618
TI  - Effect of renal sympathetic denervation on ventricular and neural remodeling.
AB  - BACKGROUND: This study assessed the therapeutic effects of renal sympathetic
      denervation (RDN) on post-myocardial infarction (MI) ventricular remodeling and
      sympathetic neural remodeling in dogs. The possible mechanisms and optimal time
      for treatment are discussed. METHODS: We randomly assigned 30 dogs to five
      groups: RDN 1 week before MI (RDN1w + MI; n = 6), RDN 1 week after MI (MI1w +
      RDN; n = 6), RDN 2 weeks after MI (MI2w + RDN; n = 6), control (N; n = 6), and MI
      (n = 6). A canine model of myocardial infarction was established by
      interventional occlusion with a gelatin sponge via the femoral artery. Brain
      natriuretic peptide (BNP) and endothelin-1 (ET-1) levels were measured and
      echocardiography was performed to assess cardiac function and heart size. All
      dogs were killed at the end of the experiment and samples of cardiac and renal
      arteries were obtained. The expression of matrix metalloproteinase (MMP)-2 and
      MMP-9 in cardiac and of tyrosine hydroxylase (TH) in renal arteries was assessed
      by immunohistochemistry. Sympathetic innervations in the infarction border zone
      were investigated via Western blotting and real-time PCR. RESULTS: Left
      ventricular function in the MI group decreased significantly, while plasma BNP
      and ET-1 levels as well as MMP-2 and MMP-9 expression increased. Compared with
      the MI group, the RD groups showed significantly reduced MMP-2, MMP-9, TH, and
      growth-associated protein (GAP) 43 expression in the RDN1w + MI, MI1w + RDN, and
      MI2w + RDN groups was significantly improved. Additionally, the expression of TH
      in renal arteries decreased after RDN. CONCLUSION: RDN has preventive and
      therapeutic effects on post-MI ventricular remodeling and sympathetic neural
      remodeling. The mechanism of RDN is likely mediated through restraint of renal
      sympathetic nerve activity.

PMID- 29651619
TI  - Silk fibroin-based woven endovascular prosthesis with heparin surface
      modification.
AB  - A novel seamless silk fibroin-based endovascular prosthesis (SFEPs) with
      bifurcated woven structure and anticoagulant function for the improvement of
      patency is described. The SFEPs were prepared from silk fibroin (SF) and
      polyester filaments using an installed weaving machine. The production processing
      parameters were optimized using orthogonal design methods. The inner surface of
      SFEPs was modified with polyethylenimine (PEI) and EDC/NHS-activated low
      molecular-weight heparin (LMWH) to enhance anticoagulant function. The surface
      morphology and mechanical properties of the SFEPs were evaluated according to
      standard protocols. The thickness of modified SFEPs was lower than 0.085 +/-
      0.004 mm and water permeability was lower than 5.19 +/- 0.30 mL/(cm2 * min). The
      results of mechanical properties showed that the diametral tensile strength and
      burst strength reached 61.6 +/- 1.8 and 23.7 +/- 2.2 MPa, respectively. Automatic
      coagulometer and energy-dispersive X-ray (EDX) confirmed LMWH immobilization on
      the surface of the SFEPs and the blood compatibility was improved with the
      heparin modification with PEI polymerization. In conclusion, the new prosthesis
      has potential applications in the blood vessel repairs where minimal thickness
      but superior mechanical strength and biocompatibility are important.

PMID- 29651620
TI  - Mental health problems and their association to violence and maltreatment in a
      nationally representative sample of Tanzanian secondary school students.
AB  - PURPOSE: Little is known about the prevalence of mental health problems among
      adolescents in Sub-Saharan Africa. Research consistently determined violence and
      maltreatment to be important risk factors. In this study, we examined the
      prevalence of mental health problems among adolescents in Tanzania, as well as
      the association with exposure to violence and maltreatment. METHODS: We
      administered a set of questionnaires (e.g., strength and difficulties
      questionnaire; conflict tactic scale) to a nationally representative sample of
      700 Tanzanian secondary school children (52% girls; age 14.92 years, SD = 1.02)
      and 333 parents or primary caregivers (53% females; age 43.47 years, SD = 9.02).
      RESULTS: 41% of the students reported an elevated level of mental health problems
      (emotional problems 40%, peer problems 63%, conduct problems 45%, hyperactivity
      17%) in the past 6 months. Concordantly, 31% of parents reported observing an
      elevated level of mental health problems in their children (emotional problems
      37%, peer problems 54%, conduct problems 35%, hyperactivity 17%). After
      controlling for other risk factors, we found significant associations between
      physical violence by parents and adolescent's mental health problems reported by
      students (beta = 0.15) and their parents (beta = 0.33). CONCLUSIONS: Our findings
      suggest a high prevalence of mental health problems using screening tools among
      secondary school students in Tanzania as well as an association between physical
      violence by parents and adolescents' mental health problems. Our findings
      emphasize the need to inform the population at large about the potentially
      adverse consequences associated with violence against children and adolescents.

PMID- 29651621
TI  - Characteristics and motivations of volunteers providing one-to-one support for
      people with mental illness: a survey in Austria.
AB  - PURPOSE: Large numbers of volunteers provide one-to-one support for people with
      mental illness, sometimes referred to as befriending. However, there has been
      very little research on their characteristics and motivations. This study aimed
      to assess the personal characteristics and motivations of such volunteers across
      different regions in Austria. METHODS: Questionnaires assessing characteristics
      and motivations were distributed to 663 volunteers providing befriending for
      people with mental illness within volunteering programmes organised in four
      Austrian regions. RESULTS: Questionnaires were completed and returned by 360 out
      of 663 approached volunteers (response rate 54%). Whilst most socio-demographic
      characteristics were widely distributed, 78% were female; 42% reported to have a
      family member and 56% a friend with a mental illness. Most volunteers cited
      motivations to do something both for others (e.g. "feel a responsibility to help
      others") and for themselves (e.g. "enhance my awareness of mental health
      issues"). When the total group was divided into four subgroups in a cluster
      analysis based on their socio-demographic characteristics, a subgroup of female,
      single and younger volunteers in full-time employment expressed motivations to
      achieve something for themselves significantly more often than other subgroups.
      CONCLUSIONS: The study provides the largest sample of volunteers in befriending
      programmes for people with mental illness in the research literature to date. The
      findings suggest that people with different characteristics can be recruited to
      volunteer for befriending programmes. Recruitment strategies and supervision
      arrangements should consider motivations both to help others and to achieve
      something for themselves, and may be varied for specific volunteer subgroups.

PMID- 29651622
TI  - Utilization of psychiatric care and antidepressants among people with different
      severity of depression: a population-based cohort study in Stockholm, Sweden.
AB  - PURPOSE: To identify how severity of depression predicts future utilization of
      psychiatric care and antidepressants. METHODS: Data derived from a longitudinal
      population-based study in Stockholm, Sweden, include 10443 participants aged 20
      64 years. Depression was assessed by Major Depression Inventory and divided into
      subsyndromal, mild, moderate and severe depression. Outcomes were the first time
      of hospitalization, specialized outpatient care and prescribed drugs obtained
      from national register records. The association between severity of depression
      and outcomes was tested by Cox regression analysis, after adjusting for gender,
      psychiatric treatment history and socio-environmental factors. RESULTS: The
      cumulative incidences of hospitalizations, outpatient care and antidepressants
      were 4.0, 11.2, and 21.9% respectively. Compared to the non-depressed group,
      people with different severity of depression (subsyndromal, mild, moderate and
      severe depression) all had significantly higher risk of all three psychiatric
      services (all log-rank test P < 0.001). Use of psychiatric care and
      antidepressants increased by rising severity of depression. Although the
      associations between severity of depression and psychiatric services were
      significant, the dose relationship was not present in people with previous
      psychiatric history or after adjusting for gender and other factors. CONCLUSIONS:
      People with subsyndromal to severe depression all have increased future
      psychiatric service utilization compared to non-depressed people.

PMID- 29651623
TI  - Facile synthesis of surface-functionalized magnetic nanocomposites for
      effectively selective adsorption of cationic dyes.
AB  - A new magnetic nano-adsorbent, polycatechol modified Fe3O4 magnetic nanoparticles
      (Fe3O4/PCC MNPs) were prepared by a facile chemical coprecipitation method using
      iron salts and catechol solution as precursors. Fe3O4/PCC MNPs owned negatively
      charged surface with oxygen-containing groups and showed a strong adsorption
      capacity and fast adsorption rates for the removal of cationic dyes in water. The
      adsorption capacity of methylene blue (MB), cationic turquoise blue GB (GB),
      malachite green (MG), crystal violet (CV) and cationic pink FG (FG) were 60.06 mg
      g- 1, 70.97 mg g- 1, 66.84 mg g- 1, 66.01 mg g- 1 and 50.27 mg g- 1,
      respectively. The adsorption mechanism was proposed by the analyses of the
      adsorption isotherms and adsorption kinetics of cationic dyes on Fe3O4/PCC MNPs.
      Moreover, the cationic dyes adsorbed on the MNPs as a function of contact time,
      pH value, temperature, coexisting cationic ions and ion strength were also
      investigated. These results suggested that the Fe3O4/PCC MNPs is promising to be
      used as a magnetic adsorbent for selective adsorption of cationic dyes in
      wastewater treatment.

PMID- 29651626
TI  - Current Topics in the Management of Acute Traumatic Spinal Cord Injury.
AB  - Acute traumatic spinal cord injury (SCI) affects more than 250,000 people in the
      USA, with approximately 17,000 new cases each year. It continues to be one of the
      most significant causes of trauma-related morbidity and mortality. Despite the
      introduction of primary injury prevention education and vehicle safety devices,
      such as airbags and passive restraint systems, traumatic SCI continues to have a
      substantial impact on the healthcare system. Over the last three decades, there
      have been considerable advancements in the management of patients with traumatic
      SCI. The advent of spinal instrumentation has improved the surgical treatment of
      spinal fractures and the ability to manage SCI patients with spinal mechanical
      instability. There has been a concomitant improvement in the nonsurgical care of
      these patients with particular focus on care delivered in the pre-hospital,
      emergency room, and intensive care unit (ICU) settings. This article represents
      an overview of the critical aspects of contemporary traumatic SCI care and notes
      areas where further research inquiries are needed. We review the pre-hospital
      management of a patient with an acute SCI, including triage, immobilization, and
      transportation. Upon arrival to the definitive treatment facility, we review
      initial evaluation and management steps, including initial neurological
      assessment, radiographic assessment, cervical collar clearance protocols, and
      closed reduction of cervical fracture/dislocation injuries. Finally, we review
      ICU issues including airway, hemodynamic, and pharmacological management, as well
      as future directions of care.

PMID- 29651625
TI  - Clinical Characteristics and Prognosis of Severe Anti-N-methyl-D-aspartate
      Receptor Encephalitis Patients.
AB  - BACKGROUND AND PURPOSE: Data concerning the characteristics and duration of the
      critical manifestations, treatment response, and long-term outcomes of severe
      anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis patients compared to
      those of non-severe patients are limited. This observational study was performed
      to explore the clinical characteristics and long-term outcomes of severe anti
      NMDAR encephalitis patients. METHODS: According to their characteristics on
      admission to the neurology intensive care unit, patients with anti-NMDAR
      encephalitis were divided into a severe group and a non-severe group. The
      demographics, clinical manifestations, main accessory examinations,
      immunotherapy, and outcomes of patients were recorded. Statistical analyses were
      employed to examine the differences in each observed indicator between the severe
      and non-severe groups. RESULTS: This study enrolled 111 patients with anti-NMDAR
      encephalitis, including 59 males and 52 females with a mean age of 27.7 +/- 13.7
      years; 39 (35.1%) patients were in the severe group, and 72 (64.9%) patients were
      in the non-severe group. Compared to the non-severe group, the severe group
      exhibited a higher proportion of epilepsy, involuntary movement, disturbance of
      consciousness, autonomic dysfunction, and central hypoventilation. The
      cerebrospinal fluid (CSF) of all patients was positive for the NMDAR antibody,
      but only 57 patients (51.4%) tested positive for the NMDAR antibody in the blood.
      The proportion of patients with a strong positive NMDAR antibody titer in the
      severe group (48.7%) was higher than that in the non-severe group (29.2%). The
      proportion of patients receiving intravenous gamma immunoglobulin in the severe
      group was higher than that in the non-severe group (P = 0.003), and only patients
      in the severe group received plasma exchange, intravenous rituximab, and
      cyclophosphamide treatment. No significant difference was observed in the
      prognosis between the severe group and the non-severe group after 6 months and
      during long-term follow-up. CONCLUSION: Most severe anti-NMDAR encephalitis
      patients will eventually achieve good long-term prognoses after receiving early,
      positive and unremitting combined immunotherapy and life support.

PMID- 29651624
TI  - In papillary thyroid carcinoma, expression by immunohistochemistry of BRAF V600E,
      PD-L1, and PD-1 is closely related.
AB  - Immune checkpoint inhibitor therapies targeting PD-L1/PD-1 have been shown to be
      effective in treating several types of human cancer. In papillary thyroid
      carcinoma (PTC), little is known about the expression of PD-L1/PD-1 in the tumor
      microenvironment or its potential correlation with BRAF V600E mutation status. In
      this study, we examined the expression of PD-L1, PD-1, and BRAF V600E in PTC by
      immunohistochemistry and investigated the clinical significance of expression
      status. We studied the expression of PD-L1, PD-1, and BRAF V600E by
      immunohistochemical staining in 110 cases of PTC with a diameter > 1 cm. Cases
      with a background of chronic lymphocytic thyroiditis (CLT) were excluded, as
      differentiating lymphocytes in the context of CLT from tumor-infiltrating
      lymphocytes (TILs) is difficult. We classified PD-L1+/PD-1+ expression as type 1
      (41%), PD-L1-/PD-1- as type 2 (17%), PD-L1+/PD-1- as type 3 (5%), and PD-L1-/PD
      1+ as type 4 (37%). Significant correlations were found between expression of
      BRAF V600E and that of PD-L1 and PD-1. The positive correlation observed between
      expression of BRAF V600E and PD-L1/PD-1 suggests that immunotherapies targeting
      PD-L1/PD-1 might be effective for PTC patients with the BRAF V600E mutation,
      which are refractory to radioiodine therapy.

PMID- 29651627
TI  - Equivalence Testing of Complex Particle Size Distribution Profiles Based on Earth
      Mover's Distance.
AB  - Particle size distribution (PSD) is an important property of particulates in drug
      products. In the evaluation of generic drug products formulated as suspensions,
      emulsions, and liposomes, the PSD comparisons between a test product and the
      branded product can provide useful information regarding in vitro and in vivo
      performance. Historically, the FDA has recommended the population bioequivalence
      (PBE) statistical approach to compare the PSD descriptors D50 and SPAN from test
      and reference products to support product equivalence. In this study, the earth
      mover's distance (EMD) is proposed as a new metric for comparing PSD particularly
      when the PSD profile exhibits complex distribution (e.g., multiple peaks) that is
      not accurately described by the D50 and SPAN descriptor. EMD is a statistical
      metric that measures the discrepancy (distance) between size distribution
      profiles without a prior assumption of the distribution. PBE is then adopted to
      perform statistical test to establish equivalence based on the calculated EMD
      distances. Simulations show that proposed EMD-based approach is effective in
      comparing test and reference profiles for equivalence testing and is superior
      compared to commonly used distance measures, e.g., Euclidean and Kolmogorov
      Smirnov distances. The proposed approach was demonstrated by evaluating
      equivalence of cyclosporine ophthalmic emulsion PSDs that were manufactured under
      different conditions. Our results show that proposed approach can effectively
      pass an equivalent product (e.g., reference product against itself) and reject an
      inequivalent product (e.g., reference product against negative control), thus
      suggesting its usefulness in supporting bioequivalence determination of a test
      product to the reference product which both possess multimodal PSDs.

PMID- 29651628
TI  - Intracranial and Intraocular Pressure at the Lamina Cribrosa: Gradient Effects.
AB  - PURPOSE OF REVIEW: A pressure difference between the intraocular and intracranial
      compartments at the site of the lamina cribrosa has been hypothesized to have a
      pathophysiological role in several optic nerve head diseases. This paper reviews
      the current literature on the translamina cribrosa pressure difference (TLCPD),
      the associated pressure gradient, and its potential pathophysiological role, as
      well as the methodology to assess TLCPD. RECENT FINDINGS: For normal-tension
      glaucoma (NTG), initial studies indicated low intracranial pressure (ICP) while
      recent findings indicate that a reduced ICP is not mandatory. Data from studies
      on the elevated TLCPD as a pathophysiological factor of NTG are equivocal. From
      the identification of potential postural effects on the cerebrospinal fluid (CSF)
      communication between the intracranial and retrolaminar space, we hypothesize
      that the missing link could be a dysfunction of an occlusion mechanism of the
      optic nerve sheath around the optic nerve. In upright posture, this could cause
      an elevated TLCPD even with normal ICP and we suggest that this should be
      investigated as a pathophysiological component in NTG patients.

PMID- 29651629
TI  - High-normal serum thyrotropin levels and increased glycemic variability in type 2
      diabetic patients.
AB  - PURPOSE: High-normal thyrotropin (TSH) is related to reduced insulin sensitivity
      and may contribute to glycemic disorders in diabetes. We investigated the
      relationship between normal serum TSH levels and glycemic variability in
      euthyroid type 2 diabetic patients. METHODS: A total of 432 newly diagnosed type
      2 diabetic patients with euthyroid function and normal serum TSH levels were
      recruited between March 2013 and February 2017. Insulin sensitivity was evaluated
      by the Matsuda index (ISIMatsuda) following a 75-g oral glucose tolerance test.
      Multiple glycemic variability indices, including the mean amplitude of glycemic
      excursions (MAGE), mean of daily differences (MODD), and standard deviation of
      glucose (SD), were calculated from glucose data obtained with a continuous
      glucose monitoring system. Average glucose accessed by 24-h mean glucose (24-h
      MG) was also calculated. RESULTS: A normal serum TSH level was positively
      correlated with MAGE, MODD, SD, and 24-h MG (r = 0.206, 0.178, 0.186, and 0.132,
      respectively, p < 0.01). After adjusting for somatometric parameters, lipid
      profiles, ISIMatsuda, and HbA1c via multiple linear regression analysis, mean
      differences [B(95% CI)] in MAGE, MODD, SD, and 24-h MG between the patients in
      the lowest and highest quartiles of TSH levels were 0.128(0.031, 0.226),
      0.085(0.022, 0.148), 0.039(0.001, 0.078), and 0.002(-0.264, 0.267) mmol/L,
      respectively. High-normal TSH was independently associated with MAGE, MODD, and
      SD, but not 24-h MG. CONCLUSIONS: High-normal serum TSH is a significant
      additional risk factor for increased glycemic variability in type 2 diabetic
      patients.

PMID- 29651630
TI  - Speeding up Monte Carlo simulation of patchy hard cylinders.
AB  - The hard cylinder model decorated with attractive patches proved to be very
      useful recently in studying physical properties of several colloidal systems.
      Phase diagram, elastic constants and cholesteric properties obtained from
      computer simulations based on a simple hard cylinder model have been all
      successfully and quantitatively compared to experimental results. Key to these
      simulations is an efficient algorithm to check the overlap between hard
      cylinders. Here, we propose two algorithms to check the hard cylinder overlap and
      we assess their efficiency through a comparison with an existing method available
      in the literature and with the well-established algorithm for simulating hard
      spherocylinders. In addition, we discuss a couple of optimizations for performing
      computer simulations of patchy anisotropic particles and we estimate the speed-up
      which they can provide in the case of patchy hard cylinders.

PMID- 29651631
TI  - Sleep and self-care correlates before and after implantation of a left
      ventricular assist device (LVAD).
AB  - The impact of sleep on LVAD patients' self-care behaviors is unknown. This study
      examined the patterns and changes of patients sleep quality (SQ), daytime
      sleepiness (DS), instrumental activities of daily living (IADL), and self-care
      capability (SCC) before and after LVAD. In addition, the relationships among
      these variables were explored. This observational study consisted of 38 subjects
      from two VAD Centers in Michigan. The subjects completed self-reported
      demographics and psychometrically sound SQ, DS, IADL, and SCC questionnaires
      before LVAD implant and at 1, 3, and 6 months after implant. Data were analyzed
      using descriptive statistics, linear mixed models, and partial least square
      models. Subjects (mean age, 56.3 +/- 10.3 years) were predominantly white (63%),
      male (68%), married (60%), and living with caregivers (92%). Over 70% had axial
      flow LVADs implanted as bridge-to-transplant (55%). Subjects' SQ was poor
      throughout the study period, along with high normal-to-excessive levels of DS.
      Problems with IADL before implant were significantly reduced at 1 through 6
      months after implant. SCC ranged from "good" to "excellent" before and after
      implant. Significant relationships between SQ and IADL (beta = 0.43, p < 0.01)
      and DS and SCC (beta = - 0.62, p < 0.01) were found. In conclusion, poor SQ and
      high degrees of DS were prevalent before and up to 6 months after LVAD implant.
      The data inferred that the improvement in IADL was associated with an improvement
      in SQ. Research is needed to clarify the negative impact of DS on SCC and explain
      the contributions of caregivers on patients' SCC over time.

PMID- 29651632
TI  - High expression of FBP17 in invasive breast cancer cells promotes invadopodia
      formation.
AB  - Metastatic spread of the cancer is usually the consequence of the activation of
      signaling pathways that generate cell motility and tissue invasion. Metastasis
      involves the reorganization of cytoskeleton and cell shape for the swift movement
      of the cells through extracellular matrix. Previously, we have described the
      invasive and metastatic role played by one of the members (Toca-1) of CIP4
      subfamily of F-BAR proteins. In the present study, we address the role of another
      member (FBP17) of same family in the invasion breast cancer cells. Here, we
      report that the formin-binding protein 17 (FBP17) is highly expressed at both
      mRNA and protein levels in breast cancer cells. The study showed the association
      of FBP17 with cytoskeletal actin regulatory proteins like dynamin and cortactin.
      To determine its role in extracellular matrix (ECM) degradation, we achieved
      stable knockdown of FBP17 in MDA-MB-231 cells. FBP17 knockdown cells showed a
      defect and were found to be compromised in the degradation of ECM indicating the
      role of FBP17 in the invasion of breast cancer cells. Our results suggest that
      FBP17 is highly expressed in breast cancer cells and facilitates the invasion of
      breast cancer cells.

PMID- 29651633
TI  - Identification of a Sorbicillinoid-Producing Aspergillus Strain with
      Antimicrobial Activity Against Staphylococcus aureus: a New Polyextremophilic
      Marine Fungus from Barents Sea.
AB  - The exploration of poorly studied areas of Earth can highly increase the
      possibility to discover novel bioactive compounds. In this study, the cultivable
      fraction of fungi and bacteria from Barents Sea sediments has been studied to
      mine new bioactive molecules with antibacterial activity against a panel of human
      pathogens. We isolated diverse strains of psychrophilic and halophilic bacteria
      and fungi from a collection of nine samples from sea sediment. Following a full
      bioassay-guided approach, we isolated a new promising polyextremophilic marine
      fungus strain 8Na, identified as Aspergillus protuberus MUT 3638, possessing the
      potential to produce antimicrobial agents. This fungus, isolated from cold
      seawater, was able to grow in a wide range of salinity, pH and temperatures. The
      growth conditions were optimised and scaled to fermentation, and its produced
      extract was subjected to chemical analysis. The active component was identified
      as bisvertinolone, a member of sorbicillonoid family that was found to display
      significant activity against Staphylococcus aureus with a minimum inhibitory
      concentration (MIC) of 30 MUg/mL.

PMID- 29651634
TI  - Air quality and passenger comfort in an air-conditioned bus micro-environment.
AB  - In this study, passenger comfort and the air pollution status of the micro
      environmental conditions in an air-conditioned bus were investigated through
      questionnaires, field measurements, and a numerical simulation. As a subjective
      analysis, passengers' perceptions of indoor environmental quality and comfort
      levels were determined from questionnaires. As an objective analysis, a numerical
      simulation was conducted using a discrete phase model to determine the diffusion
      and distribution of pollutants, including particulate matter with a diameter < 10
      MUm (PM10), which were verified by experimental results. The results revealed
      poor air quality and dissatisfactory thermal comfort conditions in Jinan's air
      conditioned bus system. To solve these problems, three scenarios (schemes A, B,
      C) were designed to alter the ventilation parameters. According to the results of
      an improved simulation of these scenarios, reducing or adding air outputs would
      shorten the time taken to reach steady-state conditions and weaken the airflow or
      lower the temperature in the cabin. The airflow pathway was closely related to
      the layout of the air conditioning. Scheme B lowered the temperature by 0.4 K and
      reduced the airflow by 0.01 m/s, while scheme C reduced the volume concentration
      of PM10 to 150 MUg/m3. Changing the air supply angle could further improve the
      airflow and reduce the concentration of PM10. With regard to the perception of
      airflow and thermal comfort, the scheme with an airflow provided by a 60 degrees 
      nozzle was considered better, and the concentration of PM10 was reduced to 130
      MUg/m3.

PMID- 29651635
TI  - Effects of Probiotic Supplementation on Trimethylamine-N-Oxide Plasma Levels in
      Hemodialysis Patients: a Pilot Study.
AB  - Components present in the diet, L-carnitine, choline, and betaine are metabolized
      by gut microbiota to produce metabolites such as trimethylamine-N-oxide (TMAO)
      that appear to promote cardiovascular disease in chronic kidney disease (CKD)
      patients. The objective of this pilot study was to evaluate the effects of
      probiotic supplementation for 3 months on plasma TMAO levels in CKD patients on
      hemodialysis (HD). A randomized, double-blind trial was performed in 21 patients
      [54.8 +/- 10.4 years, nine men, BMI 26.1 +/- 4.8 kg/m2, dialysis vintage 68.5
      (34.2-120.7) months]. Ten patients were randomly allocated to the placebo group
      and 11 to the probiotic group [three capsules, totaling 9 * 1013 colony-forming
      units per day of Streptococcus thermophilus (KB19), Lactobacillus acidophilus
      (KB27), and Bifidobacteria longum (KB31). Plasma TMAO, choline, and betaine
      levels were measured by LC-MS/MS at baseline and after 3 months. While TMAO did
      not change after probiotic supplementation, there was a significant increase in
      betaine plasma levels. In contrast, the placebo group showed a significant
      decrease in plasma choline levels. Short-term probiotic supplementation does not
      appear to influence plasma TMAO levels in HD patients. Long-term studies are
      needed to determine whether probiotics may affect TMAO production in CKD
      patients.

PMID- 29651636
TI  - Aflatoxin M1 Detoxification Ability of Probiotic Lactobacilli of Indian Origin in
      In vitro Digestion Model.
AB  - Aflatoxin M1 (AFM1) is known to be a potent carcinogen and continues to pose a
      public health concern through the consumption of contaminated dairy foods. It is
      anticipated that consumption of lactic acid bacteria capable of binding
      aflatoxins can reduce the risk of AFM1 on human health to a certain extent.
      Seldom reports have hinted the possibility of using lactic acid bacteria for the
      biological detoxification of AFM1. Hence, the present study was conducted to
      assess the ability of selected probiotic Lactobacillus strains for their AFM1
      binding ability in PBS and to reduce its bioaccessibility in artificially
      contaminated skim milk using an in vitro digestion model. Eleven tested probiotic
      strains illustrated various degrees of AFM1 binding ability ranging from 4.13 to
      64.16%. Five among the 11 probiotic strains were subsequently selected for
      detailed studies on the basis of highest binding potential after 24 h of
      incubation period. The stability of bacterial-AFM1 complex was assessed by
      repeated washings with AFM1 free PBS. The observation on bacterial-AFM1 complex
      stability showed small release of AFM1 in first and second wash (17.30 to 0.98%)
      where as none was detectable in the third wash. However, upon chloroform
      extraction, 88.57 to 92.30% of bound AFM1 was released from the bacterial cells
      which indicate AFM1 binding to the bacterial cell surface rather than absorption
      or degradation of AFM1 by bacterial cells. During the in vitro digestion test in
      skim milk, bioaccessibility of AFM1 was reduced to a scale of 32.61 to 52.84% in
      the presence of selected strains of probiotic lactobacilli. The present findings
      suggest that selected probiotic strains could be potentially used to mitigate the
      toxic effects of AFM1 in the contaminated milk and milk products and thereby
      enhance food safety.

PMID- 29651637
TI  - An overview of mammographic density and its association with breast cancer.
AB  - In 2017, breast cancer became the most commonly diagnosed cancer among women in
      the US. After lung cancer, breast cancer is the leading cause of cancer-related
      mortality in women. The breast consists of several components, including milk
      storage glands, milk ducts made of epithelial cells, adipose tissue, and stromal
      tissue. Mammographic density (MD) is based on the proportion of stromal,
      epithelial, and adipose tissue. Women with high MD have more stromal and
      epithelial cells and less fatty adipose tissue, and are more likely to develop
      breast cancer in their lifetime compared to women with low MD. Because of this
      correlation, high MD is an independent risk factor for breast cancer. Further,
      mammographic screening is less effective in detecting suspicious lesions in dense
      breast tissue, which can lead to late-stage diagnosis. Molecular differences
      between dense and non-dense breast tissues explain the underlying biological
      reasons for why women with dense breasts are at a higher risk for developing
      breast cancer. The goal of this review is to highlight the current molecular
      understanding of MD, its association with breast cancer risk, the demographics
      pertaining to MD, and the environmental factors that modulate MD. Finally, we
      will review the current legislation regarding the disclosure of MD on a
      traditional screening mammogram and the supplemental screening options available
      to women with dense breast tissue.

PMID- 29651638
TI  - Improvement in diagnostic performance of breast cancer: comparison between
      conventional digital mammography alone and conventional mammography plus digital
      breast tomosynthesis.
AB  - BACKGROUND: The aim of this study was to determine if the diagnostic performance
      of breast lesion examinations could be improved using both digital breast
      tomosynthesis (DBT) and conventional digital mammography (CDM). METHODS: Our
      institutional review board approved the protocol, and patients were provided the
      opportunity to opt out of the study. A total of 628 patients aged 22-91 years
      with abnormal screening results or clinical symptoms were consecutively enrolled
      between June 2015 and March 2016. All patients underwent DBT and CDM, and 1164
      breasts were retrospectively analyzed by three radiologists who interpreted the
      results based on the Breast Imaging Reporting and Data System. Categories 4 and 5
      were considered positive, and pathological results were the gold standard. The
      diagnostic performance of CDM and CDM plus DBT was compared using the mean areas
      under the receiver operating characteristic (ROC) curves. RESULTS: A total of 100
      breast cancer cases were identified. The areas under the ROC curves were 0.9160
      (95% confidence interval 0.8779-0.9541) for CDM alone and 0.9376 (95% confidence
      interval 0.9019-0.9733) for CDM plus DBT. The cut-off values for both CDM alone
      and CDM plus DBT measurements were 4, with sensitivities of 61.0% (61/100) and
      83.0% (83/100), respectively, and specificities of 99.1% (1054/1064) and 98.9%
      (1052/1064), respectively. CDM yielded 39 false-negative diagnoses, while CDM
      plus DBT identified breast cancer in 22 of those cases (56.4%). CONCLUSION: The
      combination of DBT and CDM for the diagnosis of breast cancer in women with
      abnormal examination findings or clinical symptoms proved effective and should be
      used to improve the diagnostic performance of breast cancer examinations.

PMID- 29651639
TI  - Abatacept for Treatment of Rheumatoid Arthritis: Special Focus on the Elderly.
AB  - Targeted therapies have been developed for patients with rheumatoid arthritis
      (RA) for whom prior treatment with traditional disease-modifying anti-rheumatic
      drugs has failed. The numerous different signaling pathways now targeted by
      various classes of monoclonal antibodies and small molecule inhibitors may
      complicate treatment decisions. Abatacept selectively modulates a co-stimulatory
      signal necessary for T-cell activation. Thus, abatacept is effective in biologic
      naive patients and in those for whom biologic therapy has failed. Emerging
      evidence indicates different benefits depending on patient and disease
      characteristics. In RA, the clinical goal should be clinical and radiographic
      remission to prevent structural damage and functional impairment. Nevertheless,
      the management of elderly patients with RA is often less aggressive, and the
      treat-to-target strategy is less respected in this age category than in the
      treatment of RA in younger patients. However, abatacept treatment in elderly
      patients is as effective and well-tolerated as in younger patients. This review
      summarizes recently published data on pharmacological properties; clinical and
      biological data on efficacy, drug retention, and safety, focusing on age; and
      evidence-based criteria for choosing abatacept or an alternative targeted
      therapy.

PMID- 29651640
TI  - Characteristics of New-Onset and Chronic Sleep Medication Users Among Older
      Adults: A Retrospective Study of a US Medigap Plan Population using Propensity
      Score Matching.
AB  - BACKGROUND: Prescription sleep medications are often utilized to manage sleep
      problems among older adults even though these drugs are associated with multiple
      risks. OBJECTIVE: The aim was to determine the prevalence and characteristics of
      new-onset compared to chronic sleep medication users and to examine factors
      associated with the conversion from new to chronic use. A secondary objective was
      to investigate the impact of sleep medications on health outcomes of injurious
      falls and patterns of healthcare utilization and expenditures. METHODS: A 25%
      random sample of adults >= 65 years with 3-year continuous AARP(r) Medicare
      Supplement medical and AARP(r) MedicareRx drug plan enrollment was utilized to
      identify new-onset and chronic sleep medication users. Prescription sleep
      medication drugs were defined using National Drug Codes (NDCs); falls or hip
      fractures were identified from diagnosis codes. New users had no sleep medication
      use in 2014, but initiated medication use in 2015; chronic users had at least one
      sleep medication prescription in 2014 and in 2015; both groups had follow-up
      through 2016. Characteristics associated with new users, new users who converted
      to chronic use, and chronic users were determined using multivariate logistic
      regression. Prevalence of falls, healthcare utilization and expenditures were
      regression adjusted. RESULTS: Among eligible insureds, 3 and 9% were identified
      as new-onset and chronic sleep medication users, respectively. New-onset sleep
      medication prescriptions were often associated with an inpatient hospitalization.
      The strongest characteristics associated with new users, those who converted to
      chronic use, and chronic users were sleep disorders, depression and opioid use.
      About 50% of new users had > 30 days' supply; 25% converted to chronic use with
      >= 90 days' supply. The prevalence of falls for new-onset users increased by 70%
      compared to a 22% increase among chronic users. CONCLUSION: New-onset and chronic
      sleep medication users were characterized by sleep disorders, depression and
      pain. Addressing the underlying problems associated with sleep problems among
      older adults may decrease the need for sleep medications and thus reduce the risk
      of sleep medication-related adverse events.

PMID- 29651641
TI  - Transcriptome-wide identification and expression profile analysis of the bHLH
      family genes in Camellia sinensis.
AB  - The tea plant is an important commercial horticulture crop cultivated worldwide.
      Yield and quality of this plant are influenced by abiotic stress. The bHLH family
      transcription factors play a pivotal role in the growth and development,
      including abiotic stress response, of plants. A growing number of bHLH proteins
      have been functionally characterized in plants. However, few studies have focused
      on the bHLH proteins in tea plants. In this study, 120 CsbHLH TFs were identified
      from tea plants using computational prediction method. Structural analysis
      detected 23 conservative residues, with over 50% identities in the bHLH domain.
      Moreover, 103 CsbHLH proteins were assumed to bind DNA and encompassed 98 E-Box
      binders and 85 G-Box binders. The CsbHLH proteins were grouped into 20
      subfamilies based on phylogenetic analysis and a previous classification system.
      A survey of transcriptome profiling screened 22 and 39 CsbHLH genes that were
      upregulated under heat and drought stress. Nine CsbHLH genes were validated using
      qRT-PCR. Results were approximately in accordance with transcriptome data. These
      genes could be induced by one or more abiotic stresses.

PMID- 29651643
TI  - Splenosis: a great mimicker of neoplastic disease.
AB  - Splenosis is a benign condition that can occur after splenic trauma or after
      surgery involving the spleen. These splenic implants are most often seen within
      the abdominal and pelvic cavities. On imaging, splenosis can be confused with
      multiple additional entities including metastatic disease, peritoneal
      carcinomatosis, peritoneal mesothelioma, abdominal lymphoma, renal cancer,
      hepatic adenomas, or endometriosis depending on its distribution. In all patients
      with history of splenic surgery or trauma, splenosis should be on the
      differential diagnosis of soft tissue nodules in the abdomen and pelvis,
      especially in the absence of systemic symptoms, to avoid unnecessary biopsy,
      chemotherapy, or surgery.

PMID- 29651642
TI  - Thulium laser VapoResection of the prostate versus traditional transurethral
      resection of the prostate or transurethral plasmakinetic resection of prostate
      for benign prostatic obstruction: a systematic review and meta-analysis.
AB  - PURPOSE: To compare the efficacy and safety of thulium laser VapoResection of the
      prostate (ThuVaRP) versus standard traditional transurethral resection of the
      prostate (TURP) or plasmakinetic resection of prostate (PKRP) for benign
      prostatic obstruction. METHODS: Systematic searches were performed in the
      Medline, EMBASE, the Cochrane Library, Web of Science, and CNKI in December 2017.
      The outcomes of demographic and clinical characteristics, perioperative
      variables, complications, and postoperative efficacy including International
      Prostate Symptom Score (IPSS), quality of life (QoL), maximum flow rate (Qmax),
      and postvoid residual (PVR) were assessed. RESULTS: 16 studies were selected in
      the meta-analysis including nine randomized controlled trials (RCTs) and seven
      non-RCTs. Among of them, nine studies compared ThuVaRP with PKRP, while seven
      studies compared ThuVaRP with TURP. It seemed that ThuVaRP needed longer
      operation time than TURP (WMD = 6.41, 95% CI 1.38-11.44, p = 0.01) and PKRP (WMD
      = 10.15, 95% CI 5.20-15.10, p < 0.0001). ThuVaRP was associated with less serum
      hemoglobin decreased, catheterization time, and the length of hospital stay
      compared with TURP (WMD = - 0.58, 95% CI - 0.77 to 0.38, p < 0.00001; WMD = -
      1.89, 95% CI - 2.67 to 1.11, p < 0.00001; WMD = - 2.25, 95% CI - 2.91 to 1.60, p
      < 0.00001) and PKRP (WMD = - 0.28, 95% CI - 0.46 to 0.10, p = 0.002; WMD = -
      1.88, 95% CI - 2.87 to 0.89, p = 0.0002; WMD = - 2.08, 95% CI - 2.63 to 1.54,
      p<0.00001). According to our assessment, there was no significantly difference in
      postoperative efficacy. CONCLUSIONS: The pooled data indicated that ThuVaRP had a
      nearly efficacy to TURP and PKRP based on IPSS, QoL, Qmax, and PVR. Although
      ThuVaRP was associated with longer operation time, it got distinct superiority on
      serum hemoglobin decreased, catheterization time, and hospital stay.

PMID- 29651644
TI  - The effects of ionic liquid 1-ethyl-3-methylimidazolium trifluoromethanesulfonate
      on the production of 1,3-propanediol from crude glycerol by microbial consortium.
AB  - Ionic liquids (ILs) as "green" solvents have been widely used owing to their
      excellent properties, e.g., for biodiesel production. Crude glycerol as a by
      product in biodiesel production is an ideal feedstock for the microbial
      production of 1,3-propanediol (PDO), which is a versatile bulk chemical. PDO can
      be produced by microbial consortium with the advantages of high substrate
      tolerance and narrow by-product profile. In the present study, the effect of IL 1
      ethyl-3-methylimidazolium trifluoromethanesulfonate ([Emim][TfO]) was evaluated
      on the capacity of PDO production from crude glycerol by microbial consortium
      DL38-BH. In the batch fermentation at 60 g/L crude glycerol and 10 g/L
      [Emim][TfO], the concentration and yield of PDO from glycerol increased from
      23.14 g/L and 0.45 mol/mol to 31.17 g/L and 0.60 mol/mol, respectively. Our
      results showed that [Emim][TfO] decreased the ratio of intracellular NADH to NAD+
      and increased the concentration of 3-HPA during batch fermentation. The
      activities of three key enzymes in glycerol metabolism were stimulated by
      [Emim][TfO] during the batch fermentation by microbial consortium DL38-BH.
      Compared to the control, the proportion of Klebsiella genus which could convert
      glycerol to PDO increased significantly from 79.19% to 89.49% and the other
      genera that did not produce PDO were dramatically decreased (P < 0.05) at the end
      of batch fermentation. This work demonstrated that [Emim][TfO] significantly
      improved the concentration and yield of PDO from crude glycerol by adjusting
      microbial community during batch fermentation by microbial consortium.

PMID- 29651645
TI  - Parental depressive symptoms as a risk factor for child depressive symptoms;
      testing the social mediators in internationally adopted children.
AB  - Parental depressive symptoms have shown to be associated with offspring
      depression but much of the research has been focused on maternal depression. The
      aim of our study was to investigate the extent to which depressive symptoms of
      both parents associate with offspring depressive symptoms and whether social
      factors mediate these associations using data from adopted children with no
      shared genetic background. Data were derived from the Finnish Adoption survey
      study (a subsample of adopted children aged between 9 and 12 years, n = 548).
      Parental depressive symptoms were measured using short version of the General
      Health Questionnaire and Children's Depression Inventory (CDI) was used to
      measure depressive symptoms in adoptees. Paternal depressive symptoms were
      related to the total CDI (B = 0.33, p = 0.05) and two dimensions of offspring
      depressive symptoms: negative mood (B = 0.10, p = 0.03) and interpersonal
      problems (B = 0.06, p = 0.009). These associations remained significant even when
      adjusted for child's age and gender, age at adoption, type of placement before
      adoption, continent of birth and adoptive family's SES. No associations were
      found between maternal and any dimensions of offspring depressive symptoms. No
      information about the mental health of biological parents was available. We
      interpret the results as demonstrating that intergenerational transmission of
      depressive symptoms is not solely related to shared genes. Also, the results
      highlight the association of paternal depression with offspring depressive
      symptoms.

PMID- 29651646
TI  - An Examination of Gay Couples' Motivations to Use (or Forego) Pre-exposure
      Prophylaxis Expressed During Couples HIV Testing and Counseling (CHTC) Sessions.
AB  - While many gay couples perceive themselves to have little risk for HIV
      transmission, research estimates that 35-68% of new HIV infections are
      transmitted within main partnerships. Pre-exposure prophylaxis (PrEP) is
      recommended for those partnered gay and bisexual men (GBM) who engage in sex
      outside their primary relationship or who have an HIV-positive partner. There is
      reason to believe that couples' sero-status and sexual agreement will shape
      perceptions of PrEP's personal relevance among gay couples. The current study
      examined motivations for and ambivalence towards PrEP uptake reported in a sample
      of 67 gay couples during completion of a brief CDC-recommended prevention
      intervention: Couples HIV Testing and Counseling. Findings suggest that all types
      of couples identified some circumstances in which they would consider PrEP;
      however, PrEP messaging should be crafted to avoid undermining current prevention
      strategies or threatening the trust and legitimacy of the relationship.

PMID- 29651647
TI  - An estrogen-related lifestyle score is associated with risk of postmenopausal
      breast cancer in the PLCO cohort.
AB  - PURPOSE: Healthy or unhealthy lifestyle behaviors are often adopted together. We
      aimed to investigate the combined effect of estrogen-related lifestyle factors on
      postmenopausal breast cancer risk. METHODS: Data from 27,153 women enrolled in
      the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial were used. We
      created an estrogen-related lifestyle score (ERLS) by incorporating a previously
      developed measure of estrogenic diet, alcohol intake, body mass index (BMI), and
      physical activity. The scores ranged from 0 to 6 with alcohol and BMI accounting
      for higher weights than the other factors. To evaluate the preventive
      possibilities of a low estrogen-related lifestyle and to be consistent with other
      published lifestyle scores, higher scores were set to correspond with potentially
      lower estrogenic lifestyle. The association between the ERLS and incident breast
      cancer was examined using Cox proportional hazards models. RESULTS: Participants
      with an ERLS of 4 or >= 5 had a 23% (HR 0.77; 95% CI 0.67-0.89) and 34% (HR 0.66;
      95% CI 0.56-0.78) lower risk of breast cancer, respectively, compared to those
      with an ERLS <= 2 after multivariable adjustment. Estimates were similar when
      restricting to invasive cases or estrogen receptor-positive subtypes. No single
      lifestyle component appeared to drive the association. CONCLUSIONS: Our findings
      suggest that the combined effect of a lifestyle characterized by a low estrogenic
      diet, low alcohol consumption, low body weight, and high levels of physical
      activity are associated with a reduction in postmenopausal breast cancer risk,
      possibly through an influence on estrogen metabolism.

PMID- 29651648
TI  - Body mass index and mortality in patients with gastric cancer: a large cohort
      study.
AB  - BACKGROUND: The effects of obesity on prognosis in gastric cancer are
      controversial. AIMS: To evaluate the association between body mass index (BMI)
      and mortality in patients with gastric cancer. METHODS: A single-institution
      cohort of 7765 patients with gastric cancer undergoing curative gastrectomy
      between October 2000 and June 2016 was categorized into six groups based on BMI:
      underweight (< 18.5 kg/m2), normal (18.5 to < 23 kg/m2), overweight (23 to < 25
      kg/m2), mildly obese (25 to < 28 kg/m2), moderately obese (28 to < 30 kg/m2), and
      severely obese (>= 30 kg/m2). Hazard ratios (HRs) for overall survival (OS) and
      disease-specific survival (DSS) were calculated using Cox proportional hazard
      models. RESULTS: We identified 1279 (16.5%) all-cause and 763 (9.8%) disease
      specific deaths among 7765 patients over 83.05 months (range 1.02-186.97) median
      follow-up. In multivariable analyses adjusted for statistically significant
      clinicopathological characteristics, preoperative BMI was associated with OS in a
      non-linear pattern. Compared with normal-weight patients, underweight patients
      had worse OS [HR 1.42; 95% confidence interval (CI) 1.15-1.77], whereas
      overweight (HR 0.84; 95% CI 0.73-0.97), mildly obese (HR 0.77; 95% CI 0.66-0.90),
      and moderately obese (HR 0.77; 95% CI 0.59-1.01) patients had better OS. DSS
      exhibited a similar pattern, with lowest mortality in moderately obese patients
      (HR 0.58; 95% CI 0.39-0.85). Spline analysis showed the lowest all-cause
      mortality risk at a BMI of 26.67 kg/m2. CONCLUSION: In patients undergoing
      curative gastric cancer surgery, those who were overweight or mildly-to
      moderately obese (BMI 23 to < 30 kg/m2) preoperatively had better OS and DSS than
      normal-weight patients.

PMID- 29651649
TI  - Systematic Review of the Economic Burden of Overt Hepatic Encephalopathy and
      Pharmacoeconomic Impact of Rifaximin.
AB  - BACKGROUND: Hepatic encephalopathy (HE), a common neurologic complication in
      cirrhosis, is associated with substantial disease and economic burden. Rifaximin
      is a non-systemic antibiotic that reduces the risk of overt HE recurrence and
      overt HE-related hospitalizations. OBJECTIVE: Our objective was to provide an
      overview of the direct HE-related costs and cost benefits of rifaximin,
      lactulose, and rifaximin plus lactulose. METHODS: A systematic review of PubMed
      and relevant meeting abstracts was conducted to identify publications since 1
      January 2007 reporting economic data related to HE and rifaximin and/or
      lactulose. Further, a public database and published literature were used to
      estimate current costs of hospitalization for overt HE, and potential cost
      savings of HE-related hospitalizations with rifaximin. The methodological quality
      of included studies was evaluated using the Drummond checklist. RESULTS: A total
      of 16 reports were identified for inclusion in the systematic review. Globally,
      HE-related direct costs ranged from $US5370 to $US50,120 annually per patient.
      Rifaximin was associated with shorter hospital stays and reduced healthcare
      costs. Rifaximin also has the potential to reduce overt HE-related
      hospitalization risk by 50% compared with lactulose. Rifaximin was shown to have
      a favourable pharmacoeconomic profile compared with lactulose (based on the
      incremental cost-effectiveness ratio). CONCLUSIONS: In addition to its clinical
      benefits (e.g. reduction in the risk of recurrence of overt HE, overt HE-related
      hospitalizations, favourable adverse event profile), economic data are favourable
      for the use of rifaximin in patients with a history of overt HE.

PMID- 29651650
TI  - Evaluation of options for presenting health-states from PROMIS(r) item banks for
      valuation exercises.
AB  - PURPOSE: Health status descriptive systems based on item response theory (IRT),
      such as the Patient-Reported Outcomes Measurement Information System (PROMIS(r)),
      have item banks to measure domains of health. We developed a method to present
      such banks for health-state valuation. METHODS: We evaluated four different
      presentation approaches: a single item (1S), 2 items presented separately (2S), 2
      items presented together (2T), or 5 items presented together (5T). We evaluated
      these four approaches in three PROMIS item banks (depression, physical function,
      and sleep disturbance). Adult community members valued health-state descriptions
      using the visual analog scale and standard gamble methods. We compared the
      approaches by the range of item bank theta scores captured, participants'
      assessments of difficulty (1 = very easy to 7 = very hard), and exit interviews.
      RESULTS: Participants (n = 118) ranged in age from 18 to 71; 63% were female and
      54% were white. The 1S approach captured the smallest range of theta scores. A
      monotonic relationship between theta score and mean standard gamble estimate was
      found with all approaches except 2S. Across all 3 item banks, mean difficulty
      assessments were 2.35 (1S), 2.69 (2T), 2.78 (5T), and 2.80 (2S). In exit
      interviews, participants generally found all four approaches similarly meaningful
      and realistic. CONCLUSIONS: Creating health descriptions by presenting 2 items
      maximized the range of theta while minimizing difficulty and maintaining a
      monotonic relationship with utility estimates. We recommend this approach for
      valuation of IRT-based descriptive systems such as PROMIS.

PMID- 29651651
TI  - Interactions of coffee consumption and postmenopausal hormone use in relation to
      breast cancer risk in UK Biobank.
AB  - PURPOSE: We investigated the association of coffee consumption with
      postmenopausal breast cancer risk, overall and by the status of postmenopausal
      hormone therapy (PMH). METHODS: This study included 126,182 postmenopausal women
      (2,636 with breast cancer and 123,546 without) from UK Biobank. Cancer diagnoses
      were ascertained through the linkage to the UK National Health Service Central
      Registers. Information on breast cancer risk factors and coffee consumption was
      collected at baseline and updated during follow-up. We used Cox proportional
      hazards regression to evaluate associations between coffee consumption and breast
      cancer, overall and in stratified analyses by woman's PMH status (none, past,
      current). RESULTS: In the overall analysis, coffee consumption was not associated
      with breast cancer risk (Hazard Ratio [HR] 1.00, 95% CI 0.91-1.11 for 2-3
      cups/day, and HR 0.98, 95% CI 0.87-1.10 for >= 4 cups/day, p-trend = 0.69). Women
      with no PMH history who consumed >= 4 cups/day had a 16% reduced risk of breast
      cancer as compared to women who consumed < 7 cups/week (HR 0.84, 95% CI 0.71
      1.00). Among women with past PMH, those consuming >= 4 cups/day had a 22% greater
      risk of breast cancer than women consuming < 7 cups/week (HR 1.22, 95% CI 1.01
      1.47). No association was found among current PMH users. We found no significant
      interaction between PMH and coffee consumption (p = 0.24). CONCLUSIONS: Coffee
      consumption might be associated with increased breast cancer risk in women who
      used hormones in the past. Further studies are warranted to confirm these
      findings and elucidate potential biological mechanisms underlying the observed
      associations.

PMID- 29651652
TI  - Titania-Coated Silica Alone and Modified by Sodium Alginate as Sorbents for Heavy
      Metal Ions.
AB  - The novel organic-inorganic biohybrid composite adsorbent was synthesized based
      on nanosized silica-titania modified with alginate within the development of
      effective adsorbent for heavy metal ions. Effects of metal species Cu(II),
      Zn(II), Cd(II), and Pb(II); concentrations; pH; temperature; and adsorption onto
      titania-coated silica (ST20) initial or modified by sodium alginate (ST20-ALG)
      were studied. The equilibrium and kinetic data of metal ions adsorption were
      analyzed using Langmuir and Freundlich adsorption models and kinetic models:
      pseudo first order, pseudo second order, intraparticle kinetic model, and
      Elovich. The maximum sorption capacities observed were higher for the ST20-ALG
      composite compared to the initial ST20 oxide for all studied metal ions, namely
      their values for ST20-ALG were 22.44 mg g- 1 for Cu(II) adsorption, 19.95 mg g- 1
      for Zn(II), 18.85 mg g- 1 for Cd(II), and 32.49 mg g- 1 for Pb(II). Structure and
      properties of initial silica-titania ST20 and modified by sodium alginate ST20
      ALG adsorbents were analyzed using nitrogen adsorption/desorption isotherms, ATR
      FTIR, SEM-EDS, and pHpzc techniques.

PMID- 29651654
TI  - In the Telencephalon, GluN2C NMDA Receptor Subunit mRNA is Predominately
      Expressed in Glial Cells and GluN2D mRNA in Interneurons.
AB  - N-methyl-D-aspartate receptors (NMDARs) are widely distributed in the brain with
      high concentrations in the telencephalon where they modulate synaptic plasticity,
      working memory, and other functions. While the actions of the predominate GluN2
      NMDAR subunits, GluN2A and GluN2B are relatively well understood, the function of
      GluN2C and GluN2D subunits in the telencephalon is largely unknown. To better
      understand the possible role of GluN2C subunits, we used fluorescence in situ
      hybridization (FISH) together with multiple cell markers to define the
      distribution and type of cells expressing GluN2C mRNA. Using a GluN2C-KO mouse as
      a negative control, GluN2C mRNA expression was only found in non-neuronal cells
      (NeuN-negative cells) in the hippocampus, striatum, amygdala, and cerebral
      cortex. For these regions, a significant fraction of GFAP-positive cells also
      expressed GluN2C mRNA. Overall, for the telencephalon, the globus pallidus and
      olfactory bulb were the only regions where GluN2C was expressed in neurons. In
      contrast to GluN2C, GluN2D subunit mRNA colocalized with neuronal and not
      astrocyte markers or GluN2C mRNA in the telencephalon (except for the globus
      pallidus). GluN2C mRNA did, however, colocalize with GluN2D in the thalamus where
      neuronal GluN2C expression is found. These findings strongly suggest that GluN2C
      has a very distinct function in the telencephalon compared to its role in other
      brain regions and compared to other GluN2-containing NMDARs. NMDARs containing
      GluN2C may have a specific role in regulating L-glutamate or D-serine release
      from astrocytes in response to L-glutamate spillover from synaptic activity.

PMID- 29651653
TI  - Intraosseous venous malformation of the zygomatico-orbital complex. Case report
      and literature review with focus on confusions in vascular lesion terms.
AB  - Intraosseous vascular malformations (VascM) of the facial skeleton are rare
      entities, raising difficulties even today in their treatment. We present a case
      for zygomatic intraosseous venous malformation of traumatic etiology with growth
      dynamics presentation and a multidisciplinary treatment approach, with
      intravascular embolization surgical ablation and primary reconstructruction using
      a titanium patient-specific implant (PSI), and a review of the literature for
      intraosseous vascular lesions of the facial skeleton focusing on the diagnostic
      syntagms used by the involved medical personnel, to shed light on the confusions
      over these terms.

PMID- 29651656
TI  - Using Lithium in Children and Adolescents with Bipolar Disorder: Efficacy,
      Tolerability, and Practical Considerations.
AB  - Lithium has been an intriguing treatment option in psychiatry for over a century.
      While seemingly just a simple elemental compound, it has powerful treatment
      effects for both depression and bipolar disorder. The evidence base for treatment
      of pediatric bipolar disorder is relatively small, but, in recent years,
      additional clinical trial data have enabled lithium to re-emerge as a valuable
      and, in many cases, preferred treatment. Pharmacologically, lithium is complex,
      with varied effects at both intracellular and extracellular levels. As a
      treatment for bipolar disorder in pediatrics, lithium is challenging, given its
      narrow therapeutic window and myriad of potential side effects. However, the
      efficacy of lithium continues to match that of newer pharmacologic agents, and
      its tolerability has been shown to be comparable with more commonly prescribed
      medications. Lithium is still one of few drugs that have been proven to reduce
      the risk of suicidality, and it may have utility in illnesses beyond affective
      disorders. Practically, as a primary agent or as an adjunct, lithium continues to
      claim a rightful place in the treatment armamentarium of child psychiatry. New
      dosing paradigms have improved tolerability and reduced potential side effects.
      Recent evidence affirms that lithium is effective for pediatric bipolar disorder
      in multiple phases of the illness.

PMID- 29651655
TI  - Antimicrobial peptides: biochemical determinants of activity and biophysical
      techniques of elucidating their functionality.
AB  - Antimicrobial peptides (AMPs) have been established over millennia as powerful
      components of the innate immune system of many organisms. Due to their broad
      spectrum of activity and the development of host resistance against them being
      unlikely, AMPs are strong candidates for controlling drug-resistant pathogenic
      microbial pathogens. AMPs cause cell death through several independent or
      cooperative mechanisms involving membrane lysis, non-lytic activity, and/or
      intracellular mechanisms. Biochemical determinants such as peptide length,
      primary sequence, charge, secondary structure, hydrophobicity, amphipathicity and
      host cell membrane composition together influence the biological activities of
      peptides. A number of biophysical techniques have been used in recent years to
      study the mechanisms of action of AMPs. This work appraises the molecular
      parameters that determine the biocidal activity of AMPs and overviews their
      mechanisms of actions and the diverse biochemical, biophysical and microscopy
      techniques utilised to elucidate these.

PMID- 29651657
TI  - Genetic and physiological basis for antibody production by Kluyveromyces
      marxianus.
AB  - Kluyveromyces marxianus is a thermotolerant, crabtree-negative yeast, which
      preferentially directs metabolism (e.g., from the tricarboxylic acid cycle) to
      aerobic alcoholic fermentation. Thus K. marxianus has great potential for
      engineering to produce various materials under aerobic cultivation conditions. In
      this study, we engineered K. marxianus to produce and secrete a single-chain
      antibody (scFv), a product that is highly valuable but has historically proven
      difficult to generate at large scale. scFv production was obtained with strains
      carrying either plasmid-borne or genomically integrated constructs using various
      combinations of promoters (P MDH1 or P ACO1 ) and secretion signal peptides
      (KmINUss or Scalpha-MFss). As the wild-type K. marxianus secretes endogenous
      inulinase predominantly, the corresponding INU1 gene was disrupted using a
      Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-associated
      protein (CRISPR-Cas9) system to re-direct resources to scFv production. Genomic
      integration was used to replace INU1 with sequences encoding a fusion of the INU1
      signal peptide to scFv; the resulting construct yielded the highest scFv
      production among the strains tested. Optimization of growth conditions revealed
      that scFv production by this strain was enhanced by incubation at 30  degrees C
      in xylose medium containing 200 mM MgSO4. These results together demonstrate that
      K. marxianus has the potential to serve as a host strain for antibody production.

PMID- 29651658
TI  - Cardiovascular imaging 2017 in the International Journal of Cardiovascular
      Imaging.

PMID- 29651659
TI  - Current achievements and future directions in genetic engineering of European
      plum (Prunus domestica L.).
AB  - In most woody fruit species, transformation and regeneration are difficult.
      However, European plum (Prunus domestica) has been shown to be amenable to
      genetic improvement technologies from classical hybridization, to genetic
      engineering, to rapid cycle crop breeding ('FasTrack' breeding). Since the first
      report on European plum transformation with marker genes in the early 90 s,
      numerous manuscripts have been published reporting the generation of new clones
      with agronomically interesting traits, such as pests, diseases and/or abiotic
      stress resistance, shorter juvenile period, dwarfing, continuous flowering, etc.
      This review focuses on the main advances in genetic transformation of European
      plum achieved to date, and the lines of work that are converting genetic
      engineering into a contemporary breeding tool for this species.

PMID- 29651661
TI  - High Arctic lemmings remain reproductively active under predator-induced elevated
      stress.
AB  - Non-consumptive effects of predation have rarely been assessed in wildlife
      populations even though their impact could be as important as lethal effects.
      Reproduction of individuals is one of the most important demographic parameters
      that could be affected by predator-induced stress, which in turn can have
      important consequences on population dynamics. We studied non-consumptive effects
      of predation on the reproductive activity (i.e., mating and fertilization) of a
      cyclic population of brown lemmings exposed to intense summer predation in the
      Canadian High Arctic. Lemmings were live-trapped, their reproductive activity
      (i.e., testes visible in males, pregnancy/lactation in females) assessed, and
      predators were monitored during the summers of 2014 and 2015 within a 9 ha
      predator-reduction exclosure delimited by a fence and covered by a net, and on an
      11 ha control area. Stress levels were quantified non-invasively with fecal
      corticosterone metabolites (FCM). We found that FCM levels of lemmings captured
      outside the predator exclosure (n = 50) were 1.6 times higher than inside (n =
      51). The proportion of pregnant/lactating adult females did not differ between
      the two areas, nor did the proportion of adult scrotal males. We found that
      lemmings showed physiological stress reactions due to high predation risk, but
      had no sign of reduced mating activity or fertility. Thus, our results do not
      support the hypothesis of reproductive suppression by predator-induced stress.

PMID- 29651660
TI  - Comparative analysis of transcriptome in two wheat genotypes with contrasting
      levels of drought tolerance.
AB  - Drought tolerance is a complex trait that is governed by multiple genes. The
      study presents differential transcriptome analysis between drought-tolerant
      (Triticum aestivum Cv. C306) and drought-sensitive (Triticum aestivum Cv. WL711)
      genotypes, using Affymetrix GeneChip(r) Wheat Genome Array. Both genotypes
      exhibited diverse global transcriptional responses under control and drought
      conditions. Pathway analysis suggested significant induction or repression of
      genes involved in secondary metabolism, nucleic acid synthesis, protein
      synthesis, and transport in C306, as compared to WL711. Significant up- and
      downregulation of transcripts for enzymes, hormone metabolism, and stress
      response pathways were observed in C306 under drought. The elevated expression of
      plasma membrane intrinsic protein 1 and downregulation of late embryogenesis
      abundant in the leaf tissues could play an important role in delayed wilting in
      C306. The other regulatory genes such as MT, FT, AP2, SKP1, ABA2, ARF6, WRKY6,
      AOS, and LOX2 are involved in defense response in C306 genotype. Additionally,
      transcripts with unknown functions were identified as differentially expressed,
      which could participate in drought responses.

PMID- 29651662
TI  - Quantifying learning in biotracer studies.
AB  - Mixing models have become requisite tools for analyzing biotracer data, most
      commonly stable isotope ratios, to infer dietary contributions of multiple
      sources to a consumer. However, Bayesian mixing models will always return a
      result that defaults to their priors if the data poorly resolve the source
      contributions, and thus, their interpretation requires caution. We describe an
      application of information theory to quantify how much has been learned about a
      consumer's diet from new biotracer data. We apply the approach to two example
      data sets. We find that variation in the isotope ratios of sources limits the
      precision of estimates for the consumer's diet, even with a large number of
      consumer samples. Thus, the approach which we describe is a type of power
      analysis that uses a priori simulations to find an optimal sample size. Biotracer
      data are fundamentally limited in their ability to discriminate consumer diets.
      We suggest that other types of data, such as gut content analysis, must be used
      as prior information in model fitting, to improve model learning about the
      consumer's diet. Information theory may also be used to identify optimal sampling
      protocols in situations where sampling of consumers is limited due to expense or
      ethical concerns.

PMID- 29651663
TI  - Finding the molecular scaffold of nuclear receptor inhibitors through high
      throughput screening based on proteochemometric modelling.
AB  - Nuclear receptors (NR) are a class of proteins that are responsible for sensing
      steroid and thyroid hormones and certain other molecules. In that case, NR have
      the ability to regulate the expression of specific genes and associated with
      various diseases, which make it essential drug targets. Approaches which can
      predict the inhibition ability of compounds for different NR target should be
      particularly helpful for drug development. In this study, proteochemometric
      modelling was introduced to analysis the bioactivity between chemical compounds
      and NR targets. Results illustrated the ability of our PCM model for high
      throughput NR-inhibitor screening after evaluated on both internal (AUC > 0.870)
      and external (AUC > 0.746) validation set. Moreover, in-silico predicted
      bioactive compounds were clustered according to structure similarity and a series
      of representative molecular scaffolds can be derived for five major NR targets.
      Through scaffolds analysis, those essential bioactive scaffolds of different NR
      target can be detected and compared. Generally, the methods and molecular
      scaffolds proposed in this article can not only help the screening of potential
      therapeutic NR-inhibitors but also able to guide the future NR-related drug
      discovery.

PMID- 29651664
TI  - The impact of chemotherapy and its timing on survival in malignant peritoneal
      mesothelioma treated with complete debulking.
AB  - The current standard of treatment for malignant peritoneal mesothelioma (MPM) is
      cytoreductive surgery when the disease distribution is favorable. The role of
      chemotherapy, as an adjunct to surgery, remains unclear. The national database of
      mesothelioma was used to identify MPM patients who were treated with curative
      intent. Patients were divided into treatment groups: (1) chemotherapy only, (2)
      surgery only, (3) neoadjuvant chemotherapy + surgery, and (4) surgery + adjuvant
      chemotherapy. A negative control group of patients who did not receive any
      treatment was added (group 0). Totally, 1740 patients were included. Mean age was
      63.04 +/- 14.58 and 60.7% were males. The patients' distribution into the
      treatment groups was 604, 684, 169, 55, and 228 patients in groups 0-4,
      respectively, with a median survival of 3.61 +/- 0.37, 11.10 +/- 0.73, 57.41 +/-
      11.91, 52.30 +/- 7.20, and 55.00 +/- 9.19 months. The addition of chemotherapy,
      in any setting, to surgery provided an improved survival at 1 year (p = 0.006).
      This survival benefit ceased at the 2-, 3-, and 5-year checkpoints. The
      multivariate analysis identified age, sarcomatoid/biphasic histologies, nodal and
      distant metastasis, and offering no treatment or chemotherapy only as poor
      prognostic factors for overall survival. No difference in overall survival was
      noted with the addition of chemotherapy to complete debulking regardless of the
      timing. Complete debulking remains the standard treatment for MPM. The addition
      of systemic chemotherapy provides a short-term survival improvement at 1 year
      only and was similar whether given in the neoadjuvant or adjuvant setting.
      Nevertheless, it did not add a survival benefit beyond the 1-year time point.

PMID- 29651667
TI  - Association between periodontitis and chronic migraine: a case-control study.
AB  - The aim of this investigation was to examine whether chronic periodontitis (CP)
      is a risk indicator of chronic migraine (CM). We performed a case-control study
      consisted of 102 cases (patients diagnosed with CM) and 91 controls (non-CM
      individuals) matched by age and gender. Full-mouth periodontal charts,
      demographic, medical, clinical, as well as neurological data were obtained. In
      addition, high sensitive C-reactive protein serum levels were determined from
      blood samples of both cases (taken during migraine interictal period) and
      controls. The prevalence of CP was significantly higher in patients with CM
      compared to those without CM (58.8 vs. 30.8%, p < 0.0001). Logistic regression
      analysis showed that CP was significantly associated with the presence of CM,
      independently of well-known chronifying factors of migraine (OR 2.4; 95% CI 1.2
      4.7; p = 0.012). Based on our results, CP could be considered as a risk indicator
      of CM. However, more evidence is necessary to investigate if this relationship is
      causal or not.

PMID- 29651665
TI  - Evaluation and management of thromboprophylaxis in Moroccan hospitals at national
      level: the Avail-MoNa study.
AB  - Venous thromboembolism (VTE) is a common clinical problem that is associated with
      substantial morbidity and mortality. The aim of this study was to describe the
      clinical practices in VTE prophylaxis in university and peripheral hospitals in
      Morocco. This is a national, cross-sectional, multicenter, observational study
      assessing the management of the VTE risk in selected Moroccan hospitals (four
      university and three peripheral). The thromboembolic risk of the selected
      patients was assessed according to the American College of Chest Physicians
      (ACCP) guidelines (2008). We hypothesized that interventions for VTE guideline
      implementation in those hospitals may improve prophylaxis use for hospitalized
      patients. A total of 1318 patients were analyzed: 467 (35.5%) medical and 851
      (64.5%) surgical. The mean age of patients was 52.6 +/- 16.5 years, and 52.7%
      were female. A total of 51.1% patients were considered to be at risk of VTE
      according to ACCP guidelines and were eligible for thromboprophylaxis (TP).
      Medical patients were more likely to present risk factors than surgical patients
      (53.6 vs. 50.7%, respectively). TP was prescribed for 53.1% of these patients,
      57.4% in at-risk surgical patients and 50.3% in at-risk medical patients. TP was
      also prescribed for 42.9% of non-at-risk patients. The concordance between the
      recommended and the prescribed prophylaxis was poor for the total population
      (kappa = 0.110). TP did not improve sufficiently in our hospitals, even after
      implementation of the guidelines. New strategies are required to appropriately
      address TP in hospitalized patients.

PMID- 29651666
TI  - EPOCH regimen as salvage therapy for adult T-cell leukemia-lymphoma.
AB  - Adult T-cell leukemia-lymphoma (ATL) is an intractable hematopoietic malignancy
      with a very poor prognosis. Although improved responses have been achieved
      through intensive chemotherapy in newly diagnosed patients with aggressive ATL,
      most patients suffer from relapse or disease recurrence, and an effective salvage
      therapy, especially for candidates for allogeneic hematopoietic stem cell
      transplantation (allo-HSCT), is yet to be established. The efficacy of the EPOCH
      regimen has been reported for several lymphoid malignancies; however, its
      efficacy for ATL has not been sufficiently evaluated. Here, we report results of
      a study of the EPOCH regimen as a salvage therapy for ATL. We retrospectively
      analyzed patients with relapsed or refractory ATL treated in our institution,
      with EPOCH as a first salvage therapy. Fourteen patients with a median age of 58
      years were analyzed, among whom eight achieved a response, including a complete
      response in one patient and partial responses in seven. Seven patients underwent
      allo-HSCT after EPOCH therapy; however, the median overall survival (OS) could
      not be determined, whereas OS at 2 years after allo-HSCT was estimated to be
      85.7%. These results suggest that EPOCH is an option for salvage therapy in
      patients with ATL, including candidates for allo-HSCT.

PMID- 29651668
TI  - Effect of chitosan nanoparticle, QMix, and EDTA on TotalFill BC sealers' dentinal
      tubule penetration: a confocal laser scanning microscopy study.
AB  - The aim of the present study was to compare the effect of chitosan nanoparticle,
      QMix, and 17% EDTA on the penetrability of a calcium silicate-based sealer into
      dentinal tubules using a confocal laser scanning microscope (CLSM). Sixty
      mandibular premolar teeth were selected and randomly divided into three groups (n
      = 20) before root canal preparation according to the solution used in the final
      rinse protocol: chitosan, QMix, and EDTA groups. Twenty teeth of each group were
      filled with a TotalFill BC sealers' single gutta-percha cone and with 0.1%
      rhodamine B. The specimens were horizontally sectioned at 3 and 5 mm from the
      apex, and the slices were analyzed in CLSM (4*). Total percentage and maximum
      depth of sealer penetration were measured using confocal laser scanning
      microscopy with using Image J analysis software. Dentinal tubule's penetration
      depth, percentage, and area were measured using imaging software. Kruskal-Wallis
      test was used for statistical analysis. The level of significance was set at 5%.
      Results of Kruskal-Wallis analysis showed that there was a significant difference
      in the percentage and depth of sealer penetration among all groups at 3 and 5 mm
      level sections (P < 0.05). Within the groups, the minimum sealer penetration
      depth was recorded for chitosan nanoparticle group. Greater depth of sealer
      penetration was recorded at 5 mm as compared to 3 mm in all the groups. Within
      the limitation of the present study, it can be concluded that QMix and EDTA
      promoted sealer penetration superior to that achieved by chitosan nanoparticle.

PMID- 29651669
TI  - HPV Screening and Vaccination Strategies in an Unscreened Population: A
      Mathematical Modeling Study.
AB  - Human papillomavirus (HPV), a sexually transmitted infection, is the necessary
      cause of cervical cancer, the third most common cancer affecting women worldwide.
      Prevention and control strategies include vaccination, screening, and treatment.
      While HPV prevention and control efforts are important worldwide, they are
      especially important in low-income areas with a high infection rate or high rate
      of cervical cancer. This study uses mathematical modeling to explore various
      vaccination and treatment strategies to control for HPV and cervical cancer while
      using Nepal as a case study. Two sets of deterministic models were created with
      the goal of understanding the impact of various prevention and control
      strategies. The first set of models examines the relative importance of screening
      and vaccination in an unscreened population, while the second set examines
      various screening scenarios. Partial rank correlation coefficients confirm the
      importance of screening and treatment in the reduction of HPV infections and
      cancer cases even when vaccination uptake is high. Results also indicate that
      less expensive screening technologies can achieve the same overall goal as more
      expensive screening technologies.

PMID- 29651670
TI  - Disease Extinction Versus Persistence in Discrete-Time Epidemic Models.
AB  - We focus on discrete-time infectious disease models in populations that are
      governed by constant, geometric, Beverton-Holt or Ricker demographic equations,
      and give a method for computing the basic reproduction number, [Formula: see
      text]. When [Formula: see text] and the demographic population dynamics are
      asymptotically constant or under geometric growth (non-oscillatory), we prove
      global asymptotic stability of the disease-free equilibrium of the disease
      models. Under the same demographic assumption, when [Formula: see text], we prove
      uniform persistence of the disease. We apply our theoretical results to specific
      discrete-time epidemic models that are formulated for SEIR infections, cholera in
      humans and anthrax in animals. Our simulations show that a unique endemic
      equilibrium of each of the three specific disease models is asymptotically stable
      whenever [Formula: see text].

PMID- 29651673
TI  - Chinese Medicine in Treatment of A Patient with Acute Extensive Anterior
      Myocardial Infarction Complicated by Shock after Percutaneous Coronary
      Intervention.

PMID- 29651671
TI  - Are endometrial cancer radiotherapy results age related?
AB  - OBJECTIVE: To analyze the impact of age on radiotherapy results based on cancer
      specific survival (CSS), vaginal-cuff relapses (VCR) and complications analysis
      in 438 patients with endometrial carcinoma (EC) receiving postoperative
      radiotherapy (PRT) divided into three age groups for analysis. MATERIALS AND
      METHODS: From 2003 to 2015, 438 patients with EC were treated with PRT and
      divided into three age groups: Group-1: 202 patients < 65 years; Group-2: 210
      patients >= 65 and < 80 years; Group-3: 26 patients >= 80 years. Vaginal toxicity
      was assessed using the objective LENT-SOMA criteria and RTOG scores were recorded
      for the rectum, bladder, and small bowel. STATISTICS: Chi square and Student's t
      tests, Kaplan-Meier survival study for analysis of CSS. RESULTS: The mean follow
      up was 5.6 years in Group-1, 5.6 years in Group-2 and 6.3 years in Group-3 (p =
      0.38). No differences were found among the groups in distribution of stage,
      grade, myometrial invasion, Type 1 vs. 2 EC and VLSI (p = 0.97, p = 0.52, p =
      0.35, p = 0.48, p = 0.76, respectively). There were no differences in rectal,
      bladder and vagina late toxicity (p = 0.46, p = 0.17, p = 0.75, respectively). A
      better CSS at 5 years was found in Group-1 (p = 0.006), and significant
      differences were found in late severe small bowel toxicity in Group-3 (p =
      0.005). VCR was increased in Group-3 (p = 0.017). CONCLUSIONS: Patients >= 65
      years had a worse outcome in comparison to younger patients. Late vaginal, rectal
      and bladder toxicities were similar in the three groups, although an increase of
      severe late small bowel toxicity led to IMRT in patients >= 80 years. Further
      larger studies are needed including quality of life analysis in patients >= 80
      years.

PMID- 29651672
TI  - Factors associated with anxiety and depression in cancer patients prior to
      initiating adjuvant therapy.
AB  - OBJECTIVE: Anxiety and depression affect cancer patients' quality of life. Our
      objectives were to determine the prevalence of anxiety and depression and analyze
      the association between positive psychological factors, sociodemographic factors,
      and clinical factors in oncological patients initiating adjuvant treatment.
      METHODS: A prospective, multicenter cohort of 600 consecutive patients completed
      the Brief Symptom Inventory, Mini-Mental Adjustment to Cancer, Life Orientation
      Scale-Revised, and Multidimensional Scale of Perceived Social Support
      questionnaires. RESULTS: Prevalence of anxiety and depression was 49.8 and 36.6%,
      respectively. Women and younger individuals were more anxious and depressed than
      men and seniors. Employed participants suffered more anxiety than retirees, and
      singles exhibited more depression than married or partnered subjects. Logistic
      regression analysis showed that hope, optimism, social support, being male, and
      older were significantly associated with a lower risk of anxiety and depression
      (p < 0.001). CONCLUSIONS: The high prevalence of anxiety and depression among
      Spaniards with cancer starting adjuvant chemotherapy suggests that more attention
      should be paid to mental health in these individuals. These findings are
      important for cancer patients because they can benefit from interventions that
      increase positive psychological factors such as hope, optimism, and social
      support to reduce anxiety and depression.

PMID- 29651674
TI  - Intestinal Microbiota and Kidney Diseases.
AB  - Kidney diseases are common and the incidence rate is increasing. Gut microbiota
      is involved in metabolic and immune regulation of the host. Genetic, alimentary
      and environmental disease factors may change gut flora and increase opportunistic
      and pathogenic bacteria, contributing to immune or non-immune mediated kidney
      diseases including IgA nephropathy and diabetic nephropathy. Additionally,
      bacterial metabolites may be a source of uremic toxins. Thus, identification of
      diversity, composition, and metabolic and immunologic features of gut bacteria in
      chronic kidney diseases may help understand pathogenetic mechanism and develop
      therapy for diseases.

PMID- 29651675
TI  - Tackling Osteoarthritic Knee Pain with Electroacupuncture.
AB  - Electroacupuncture (EA) has been widely used in pain relief. Clinical evidence
      has revealed its unique advantages and effectiveness in alleviating pain. Studies
      on EA and pain relief have revealed that EA displays greater analgesic effects
      for different types of pain in comparison to manual acupuncture. Here, we
      reviewed the clinical application and mechanism of EA in treating osteoarthritic
      knee pain and its influence factors in curative effect.

PMID- 29651676
TI  - Essence of "Shen (Kidney) Controlling Bones": Conceptual Analysis Based on
      Hypothalamic-Pituitary-Adrenal-Osteo-Related Cells Axis.
AB  - As a traditional concept of Chinese medicine (CM), the theory of "Shen (Kidney)
      controlling bones" has been gradually proven. And in modern allopathic medicine,
      the multiple mechanisms of bone growth, development and regeneration align with
      the theory. Shen deficiency as a pathological condition has a negative effect on
      the skeleton of body, specifically the disorder of bone homeostasis. Present
      studies indicate that Shen deficiency shares a common disorder characterized by
      dysfunction of hypothalamic-pituitary-adrenal (HPA) axis. HPA axis may be an
      important regulator of bone diseases with abnormal homeostasis. Therefore, we
      posit the existence of hypothalamic-pituitary-adrenal-osteo-related cells axis:
      cells that comprise bone tissue (osteo-related cells) are targets under the
      regulation of HPA axis in disorder of bone homeostasis. Chinese herbs for
      nourishing Shen have potential in the development of treatments for disorder of
      bone homeostasis.

PMID- 29651677
TI  - [Antifreeze poisoning : The case of a patient with repeated ethylene glycol
      poisoning].
AB  - Ethylene glycol poisoning of incidental or suicidal intention can cause life
      threatening metabolic acidosis, diverse secondary damage, and even lead to death.
      Beside hemodialysis effective therapy consists of the administration of
      fomepizole and ethanol. We describe a patient after repeated ethylene glycol
      poisoning with high anion gap metabolic acidosis and acute renal failure. Using
      hemodialysis, with dialysate containing a specific amount of ethanol, and
      intravenous ethanol administration we were able to prevent severe secondary organ
      damage.

PMID- 29651678
TI  - Performance of the 2015 US Preventive Services Task Force Screening Criteria for
      Prediabetes and Undiagnosed Diabetes.
AB  - BACKGROUND: In 2015, The US Preventive Services Task Force (USPSTF) recommended
      screening for prediabetes and undiagnosed diabetes (collectively called
      dysglycemia) among adults aged 40-70 years with overweight or obesity. The
      recommendation suggests that clinicians consider screening earlier in people who
      have other diabetes risk factors. OBJECTIVE: To compare the performance of
      limited and expanded screening criteria recommended by the USPSTF for detecting
      dysglycemia among US adults. DESIGN: Cross-sectional analysis of survey and
      laboratory data collected from nationally representative samples of the civilian,
      noninstitutionalized US adult population. PARTICIPANTS: A total of 3643 adults
      without diagnosed diabetes who underwent measurement of hemoglobin A1c (A1c),
      fasting plasma glucose (FPG), and 2-h plasma glucose (2-h PG). MAIN MEASURES:
      Screening eligibility according to the limited criteria was based on age 40 to 70
      years old and overweight/obesity. Screening eligibility according to the expanded
      criteria was determined by meeting the limited criteria or having >= 1 of the
      following risk factors: family history of diabetes, history of gestational
      diabetes or polycystic ovarian syndrome, and non-white race/ethnicity.
      Dysglycemia was defined by A1c >= 5.7%, FPG >= 100 mg/dL, and/or 2-h PG >= 140
      mg/dL. KEY RESULTS: Among the US adult population without diagnosed diabetes,
      49.7% had dysglycemia. Screening based on the limited criteria demonstrated a
      sensitivity of 47.3% (95% CI, 44.7-50.0%) and specificity of 71.4% (95% CI, 67.3
      75.2%). The expanded criteria yielded higher sensitivity [76.8% (95% CI, 73.5
      79.8%)] and lower specificity [33.8% (95% CI, 30.1-37.7%)]. Point estimates for
      the sensitivity of the limited criteria were lower in all minority groups and
      significantly different for Asians compared to non-Hispanic whites [29.9% (95%
      CI, 23.4-37.2%) vs. 49.8% (95% CI, 45.9-53.7%); P < .001]. CONCLUSIONS: Diabetes
      screening that follows the limited USPSTF criteria will identify approximately
      half of US adults with dysglycemia. Screening other high-risk subgroups defined
      in the USPSTF recommendation would improve detection of dysglycemia and may
      reduce associated racial/ethnic disparities.

PMID- 29651679
TI  - Biodegradable Ingredient-Based Emulgel Loaded with Ketoprofen Nanoparticles.
AB  - Biodegradable materials are extensively employed to design nanocarriers that
      mimic extracellular environment in arthritis. The aim of this study was to
      formulate and characterize biocompatible, biodegradable ketoprofen-loaded
      chitosan-chondroitin sulfate (CHS-CS) nanoparticles with natural ingredients for
      transdermal applications. Polymers used in the design of nanocarriers are
      biodegradable and produce synergistic anti-inflammatory effect for the treatment
      of arthritis. For transdermal application, argan oil-based emulgel is utilized to
      impart viscosity to the formulation. Furthermore, naturally occurring argan oil
      synergizes anti-inflammatory effect of formulation and promotes skin penetration.
      CHS and CS form nanoparticles by polyelectrolyte complex formation or complex
      coacervation at pH 5.0. These particles were loaded into argan oil-based emulgel.
      Employing this method, nanoparticles were formulated with particle size in the
      range of 300-500 nm. These nanocarriers entrapped ketoprofen and showed more than
      76% encapsulation efficiency and 77% release of the ketoprofen at pH 7.4 within
      72 h. Drug releases from CHS-CS nanoparticles by mechanism of simple diffusion.
      Nanoparticle-loaded argan oil emulgel significantly enhanced skin penetration of
      ketoprofen as compared to marketed gel (p < 0.05). Nanocarriers prepared
      successfully delivered drug through transdermal route using natural ingredients.
      Graphical abstract ?.

PMID- 29651680
TI  - Simultaneous identification and determination of flavonoids in Dendrobium
      officinale.
AB  - BACKGROUND: The quality of material medicine resources has had a considerable
      impact on the development of the health industry, which has created a bottleneck
      for traditional Chinese medicine (TCM). Dendrobium officinale, which has been
      widely used for health prevention in TCM, has become a high-nutritive health food
      that is strongly recommended by many white-collar workers and people who pay more
      attention to their health. The aim of this study was to develop a method to
      authenticate and evaluate D. officinale from different origins via simultaneous
      qualitative and quantitative analyses of flavonoid glycosides. Ultra-high
      performance liquid chromatography-electrospray ionization/mass spectrometry was
      used for the structural elucidation of the compounds. RESULTS: 9 characteristic
      peaks, including those representing 7 flavonoid C-glycosides and 2 flavonoid O
      glycosides, were identified. Additionally, the contents of 5 representative
      flavonoid glucosides in 25 batches of D. officinale from different sources were
      determined. To further investigate the different sources of the 25 batch samples,
      principal component analysis (PCA) and hierarchical cluster analysis (HCA) were
      carried out. A study on the methodology revealed that all results were reliable.
      CONCLUSIONS: This method is an efficient tool for the rapid identification of the
      different geographical origins of D. officinale and provides references for the
      quality evaluation of other natural products.

PMID- 29651681
TI  - Higher Autistic Traits Among Criminals, But No Link to Psychopathy: Findings from
      a High-Security Prison in Portugal.
AB  - The relationship between autism, criminality and psychopathy has gained increased
      attention in recent years, although research has focused on autism spectrum
      disorders, and not autistic traits. We measured autistic traits (with the Autism
      Spectrum Quotient) in a sample of 101 inmates from a high-security prison and
      compared them to a control group, using a logistic regression model that included
      age, education, psychopathology, psychopathy and attention deficit-hyperactivity
      disorder as covariates. Prisoners had more autistic traits (OR 1.13, p = 0.002)
      due to higher scores in the communication (OR 1.23) and imagination (OR 1.30)
      domains. No correlations were found between autistic and psychopathic traits. Our
      study points to the presence of autistic traits as being independent risk factors
      for imprisonment, although not associated with psychopathy.

PMID- 29651682
TI  - Addressing the Educational Needs of Children with Williams Syndrome: A Rather
      Neglected Area of Research?
AB  - Williams syndrome (WS) is a rare neurodevelopmental disorder associated with
      physical health problems, limitations in cognitive abilities and increased risk
      of mental health difficulties. This profile of complex needs may make it
      challenging to support children with WS in schools. Surprisingly, in the current
      international move for inclusion, limited research exists on the educational
      provision and academic achievements of children with WS, including the non
      existing literature on their voices and the perspectives of key stakeholders.
      This letter calls for additional research on the risk and protective factors
      associated with the educational outcomes of these children, the perspectives of
      the children themselves and the development of the evidence-base about the
      effectiveness of education intervention programs.

PMID- 29651683
TI  - Myocardial motion analysis based on an optical flow method using tagged MR
      images.
AB  - We developed a method of velocimetry based on an optical flow method using
      quantitative analyses of tagged magnetic resonance (MR) images (tagged MR-optical
      flow velocimetry, tMR-O velocimetry). The purpose of our study was to examine the
      accuracy of measurement of the proposed tMR-O velocimetry. We performed
      retrospective pseudo-electrocardiogram (ECG) gating tagged cine MR imaging on a
      rotating phantom. We optimized imaging parameters for tagged MR imaging, and
      validated the accuracy of tMR-O velocimetry. Our results indicated that the
      difference between the reference velocities and the computed velocities measured
      using optimal imaging parameters was less than 1%. In addition, we performed tMR
      O velocimetry and echocardiography on 10 healthy volunteers, for four sections of
      the heart (apical, midventricular, and basal sections aligned with the short
      axis, and a four-chamber section aligned with the long-axis), and obtained radial
      and longitudinal myocardial velocities in these sections. We compared the
      myocardial velocities obtained using tMR-O velocimetry with those obtained using
      echocardiography. Our results showed good agreement between tMR-O velocimetry and
      echocardiography in the radial myocardial velocities in three short-axial
      sections and longitudinal myocardial velocities on the midventricular portion of
      the four-chamber section in the long-axis. In the study conducted on the rotating
      phantom, tMR-O velocimetry showed high accuracy; moreover, in the healthy
      volunteers, the myocardial velocities obtained using tMR-O velocimetry were
      relatively similar to those obtained using echocardiography. In conclusion, tMR-O
      velocimetry is a potentially feasible method for analyzing myocardial motion in
      the human heart.

PMID- 29651685
TI  - Cardiogoniometry Compared to Fractional Flow Reserve at Identifying
      Physiologically Significant Coronary Stenosis: The CARDIOFLOW Study.
AB  - Cardiogoniometry (CGM) is method of 3-dimensional electrocardiographic assessment
      which has been shown to identify patients with angiographically defined, stable
      coronary artery disease (CAD). However, angiographic evidence of CAD, does not
      always correlate to physiologically significant disease. The aim of our study was
      to assess the ability of CGM to detect physiologically significant coronary
      stenosis defined by fractional flow reserve (FFR). In a tertiary cardiology
      centre, elective patients with single vessel CAD were enrolled into a prospective
      double blinded observational study. A baseline CGM recording was performed at
      rest. A second CGM recording was performed during the FFR procedure, at the time
      of adenosine induced maximal hyperaemia. A significant CGM result was defined as
      an automatically calculated ischaemia score < 0 and a significant FFR ratio was
      defined as < 0.80. Measures of diagnostic performance (including sensitivity and
      specificity) were calculated for CGM at rest and during maximal hyperaemia. Forty
      five patients were included (aged 61.1 +/- 11.0; 60.0% male), of which eighteen
      (40%) were found to have significant CAD when assessed by FFR. At rest, CGM
      yielded a sensitivity of 33.3% and specificity of 63.0%. At maximal hyperaemia
      the sensitivity and specificity of CGM was 71.4 and 50.0% respectively. The
      diagnostic performance of CGM to detect physiologically significant stable CAD is
      poor at rest. Although, the diagnostic performance of CGM improves substantially
      during maximal hyperaemia, it does not reach sufficient levels of accuracy to be
      used routinely in clinical practice.

PMID- 29651684
TI  - Social Support and Strain Across Close Relationships: A Twin Study.
AB  - Social relationships play a critical role in health and well-being throughout
      life. We analyzed the genetic and environmental variance co-variance structure
      for social support and strain across four sets of relationships including with
      one's co-twin, spouse/partner, family and friends. The sample included 5288
      Norwegian twins aged 40-80. Older people reported less support from their co-twin
      and friends and less strain from their family and friends. Genetic influences
      contribute importantly to variation across all the measures, with estimates
      ranging from 0 to 58%; variance due to shared environmental influences was most
      important for the twin-relationship, ranging from 0.11 to 0.42%. Social support
      was negatively correlated with social strain across all sets of relationships.
      With the exception of the co-twin relationship, these associations were primarily
      mediated by genetic and non-shared environmental effects.

PMID- 29651686
TI  - Tackling the Relevance of Packaging in Life Cycle Assessment of Virgin Olive Oil
      and the Environmental Consequences of Regulation.
AB  - Production and consumption of olive oil is very important in Europe, being this
      product a basic element in the Mediterranean diet since long ago. The project
      objective is two-fold: a study of the contribution of virgin olive oils (VOOs)
      usual packaging to the whole life cycle of the product and a study of the
      environmental consequences of the Spanish Government regulation on VOO packaging.
      A life cycle assessment (LCA) according to ISO 14044 has been performed using the
      CML methodology for the impact assessment. The results show that the packaging
      influence varies from 2 to 300%, depending on the impact category and type of
      packaging (glass, tin or polyethylene terephtalate). Glass, which is related to
      higher quality perception by consumers, was found to be the most influencing
      material (due to its weight); however, this impact may be fairly reduced by
      applying ecodesign strategies (such as weight reduction and recycled-glass
      percentage increase). A new Spanish regulation on the mandatory use of non
      refillable oilers in HORECA establishments (hotels, restaurants and caterings)
      aims to provide more quality assurance and better information to consumers;
      however, it was also found to mean a 74% increase in greenhouse gases emissions.
      This regulation was deeply discussed at European level and its application was
      withdraw due to consumers rejection, except for Spain. The findings of the
      present case study show that LCA and ecodesign should be important tools to be
      promoted and applied in policy making to reduce non-desirable consequences of
      regulation.

PMID- 29651687
TI  - A failure to replicate rapid syntactic adaptation in comprehension.
AB  - Language comprehension requires successfully navigating linguistic variability.
      One hypothesis for how listeners manage variability is that they rapidly update
      their expectations of likely linguistic events in new contexts. This process,
      called adaptation, allows listeners to better predict the upcoming linguistic
      input. In previous work, Fine, Jaeger, Farmer, and Qian (PLoS ONE, 8, e77661,
      2013) found evidence for syntactic adaptation. Subjects repeatedly encountered
      sentences in which a verb was temporarily ambiguous between main verb (MV) and
      reduced relative clause (RC) interpretations. They found that subjects who had
      higher levels of exposure to the unexpected RC interpretation of the sentences
      had an easier time reading the RC sentences but a more difficult time reading the
      MV sentences. They concluded that syntactic adaptation occurs rapidly in
      unexpected structures and also results in difficulty with processing the
      previously expected alternative structures. This article presents two
      experiments. Experiment 1 was designed as a follow-up to Fine et al.'s study and
      failed to find evidence of adaptation. A power analysis of Fine et al.'s raw data
      revealed that a similar study would need double the items and four times the
      subjects to reach 95% power. In Experiment 2 we designed a close replication of
      Fine et al.'s experiment using these sample size guidelines. No evidence of rapid
      syntactic adaptation was found in this experiment. The failure to find evidence
      of adaptation in both experiments calls into question the robustness of the
      effect.

PMID- 29651688
TI  - Metschnikowia mating genomics.
AB  - Genes involved in mating type determination and recognition were examined in
      Metschnikowia and related species, to gather insights on factors affecting mating
      compatibility patterns among haplontic, heterothallic yeast species of the genus.
      We confirmed the universality of the special mating locus organisation found in
      Clavispora lusitaniae across and exclusive to the family Metschnikowiaceae (i.e.,
      Metschnikowia and Clavispora). Timing of the divergence between idiomorphs was
      confirmed to coincide with the origin of the larger (CUG-ser) clade comprising
      the Debaryomycetaceae and the Metschnikowiaceae, exclusive of Cephaloascus
      fragrans. The sequence of the a mating pheromone is highly conserved within the
      large-spored Metschnikowia species, including Metschnikowia orientalis and
      Metschnikowia hawaiiana, but not Metschnikowia drosophilae or Metschnikowia
      torresii, which have a pattern of their own, as do other clades in the genus. In
      contrast, variation in alpha pheromones shows a more continuous, although
      imperfect correlation with phylogenetic distance as well as with in vivo mating
      compatibility.

PMID- 29651689
TI  - Mothers' neural responses to infant faces are associated with activation of the
      maternal care system and observed intrusiveness with their own child.
AB  - Certain infant facial characteristics, referred to as baby schema, are thought to
      automatically trigger parenting behavior and affective orientation toward
      infants. Electroencephalography (EEG) is well suited to assessing the intuitive
      nature and temporal dynamics of parenting responses, due to its millisecond
      temporal resolution. Little is known, however, about the relations between neural
      processing of infant cues and actual parenting behavior in a naturalistic
      setting. In the present study we examined the event-related potentials (ERPs) of
      mothers (N = 33) watching infant faces of varying attractiveness, in relation to
      activation of the maternal care system and the mothers' observed parenting
      behavior (sensitivity, nonintrusiveness) with their own child (2-6 years old).
      The results revealed that, irrespective of the cuteness of the infant face,
      mothers' neural processing of infant faces involved both early P1 and P2
      components (related to orienting/detecting processes) and late positive
      potentials (LPPs; related to more controlled cognitive evaluation/attentional
      engagement). Increased early detection and processing of infant faces (reflected
      by P1 and P2 activity) was related to increased activation of the parental care
      system. In later stages of face processing, increased attentional engagement with
      infant faces (as reflected by LPP activity) was associated with more
      intrusiveness of a mother with her own child during interaction. These findings
      suggest that individual variations in responses to infant stimuli are associated
      with individual differences in parental care system activation and parenting
      quality. Furthermore, the parental care system might be activated relatively
      automatically, but actual parenting and caregiving behavior requires more
      conscious control.

PMID- 29651690
TI  - Community structure analysis of rejection sensitive personality profiles: A
      common neural response to social evaluative threat?
AB  - Monitoring social threat is essential for maintaining healthy social
      relationships, and recent studies suggest a neural alarm system that governs our
      response to social rejection. Frontal-midline theta (4-8 Hz) oscillatory power
      might act as a neural correlate of this system by being sensitive to unexpected
      social rejection. Here, we examined whether frontal-midline theta is modulated by
      individual differences in personality constructs sensitive to social
      disconnection. In addition, we examined the sensitivity of feedback-related brain
      potentials (i.e., the feedback-related negativity and P3) to social feedback.
      Sixty-five undergraduate female participants (mean age = 19.69 years)
      participated in the Social Judgment Paradigm, a fictitious peer-evaluation task
      in which participants provided expectancies about being liked/disliked by peer
      strangers. Thereafter, they received feedback signaling social
      acceptance/rejection. A community structure analysis was employed to delineate
      personality profiles in our data. Results provided evidence of two subgroups: one
      group scored high on attachment-related anxiety and fear of negative evaluation,
      whereas the other group scored high on attachment-related avoidance and low on
      fear of negative evaluation. In both groups, unexpected rejection feedback
      yielded a significant increase in theta power. The feedback-related negativity
      was sensitive to unexpected feedback, regardless of valence, and was largest for
      unexpected rejection feedback. The feedback-related P3 was significantly enhanced
      in response to expected social acceptance feedback. Together, these findings
      confirm the sensitivity of frontal midline theta oscillations to the processing
      of social threat, and suggest that this alleged neural alarm system behaves
      similarly in individuals that differ in personality constructs relevant to social
      evaluation.

PMID- 29651691
TI  - Pattern of Antimicrobial Resistance among Bacterial Isolates from Urogenital
      Clinical Specimens: A Descriptive Study from the Buea Health District, Cameroon.
AB  - INTRODUCTION: Antimicrobial resistance has become a global concern and is
      particularly affecting developing countries where infectious diseases and poverty
      are endemic. The effectiveness of currently available antimicrobials is
      decreasing as a result of increasing resistant strains among clinical isolates.
      OBJECTIVES: The aim of this study was to determine the resistance pattern of
      bacterial isolates from different clinical urogenital specimens at different
      hospitals in the Buea Health District, Cameroon. METHODS: A retrospective study
      was conducted in three hospital laboratories in the Buea Health District,
      Cameroon, from June to August 2017. All culture and antimicrobial susceptibility
      test results of patients who presented at each of the laboratories for urine,
      vaginal swab or urethral swab cultures from January 2012 to December 2016 were
      included in the study. Data were analysed using SPSS Windows version 20.0. The
      comparisons between different isolates' resistance to antimicrobials were
      performed using the chi-square test. The difference in the resistance of
      urogenital isolates to various antimicrobials within different years was also
      compared by the chi-square test. RESULTS: A total of 423 bacterial isolates were
      obtained from clinical urogenital specimens such as: urine 93 (21.9%), vaginal
      swab 175 (41.4%) and urethral swab cultures 155 (36.6%). The predominant
      bacterial isolates were Staphylococcus spp. 320 (75.5%), Escherichia coli 37
      (8.7%) and Enterococcus spp. 24 (5.7%). All the isolates showed significantly
      high resistance rates to amoxicillin/clavulanic acid (67.6% resistant rate, p =
      0.025), but most isolates, except those of Staphylococcus, were relatively more
      susceptible to nitrofurantoin (82.6% susceptibility rate, p = 0.045). However,
      Staphylococcus spp. was more susceptible to ceftriaxone (91.0% susceptibility
      rate, p < 0.0001) and cefotaxime (74.4% susceptibility rate, p = 0.034).
      Generally, most of the isolates showed significantly rising rates of resistance
      to the majority of the antimicrobials tested from 2012 to 2017. CONCLUSION: Our
      findings showed a progressively rising rate of antimicrobial resistance in
      urogenital bacterial isolates over the last 5 years in the Buea Health District.
      Thus, uncontrolled and irrational use or prescription of these drugs should be
      avoided to maintain low resistance of highly susceptible antimicrobials.

PMID- 29651692
TI  - Predictive value of spectral-domain optical coherence tomography features in
      assessment of visual prognosis in eyes with acute welding arc maculopathy.
AB  - OBJECTIVE: To observe spectral-domain optical coherence tomography (SD-OCT)
      features and to determine whether baseline OCT features can be used as predictors
      of visual acuity outcome in eyes with acute welding arc maculopathy. METHODS:
      This retrospective study enrolled twenty-two eyes of eleven subjects with acute
      welding arc maculopathy. All subjects were evaluated by SD-OCT at baseline and
      final visit. The involved parameters included best-corrected visual acuity
      (BCVA), central macular thickness (CMT), the length of ellipsoid zone (EZ)
      defects, the greatest linear dimension (GLD) of outer retinal lesions, EZ
      reflectivity and relative EZ reflectivity (defined as the ratio of EZ
      reflectivity to retinal pigment epithelium reflectivity on OCT). RESULTS: Acute
      welding arc maculopathy was presented as abnormal hyperreflectivity,
      hyporeflectivity and defects of outer retinal layer in fovea on OCT. Compared
      with baseline, BCVA improved significantly accompanied by decreased GLD of outer
      retinal lesions and the length of EZ defects at final visit (P = 0.0004, P <
      0.0001 and P < 0.0001, respectively). No significant changes were shown on CMT (P
      = 0.248). In multivariate regression analysis, final BCVA was associated with
      baseline BCVA and the length of EZ defects (P = 0.012 and P = 0.045,
      respectively). However, EZ reflectivity and relative EZ reflectivity were not
      associated with final BCVA (P > 0.05). CONCLUSION: In conclusion, SD-OCT images
      clearly reveal morphological changes in outer retinal layer in acute welding arc
      maculopathy. The baseline BCVA and length of EZ defects are the strongest
      predictors of final BCVA.

PMID- 29651693
TI  - Shredder Chironomid Diets Are Influenced by Decomposition Rates of Different Leaf
      Litter Species.
AB  - The diet of shredder chironomid larvae depends on the local and temporal
      conditions of the food resources. We analysed the gut content of shredder
      chironomid larvae that colonised the leaf litter of three riparian species:
      Hedychium coronarium, Pteridium arachnoideum and Magnolia ovata. We hypothesised
      that the differences in the decomposition rates of leaf litter species influence
      the consumption of plant tissue by shredder chironomid taxa over time. We
      incubated perforated bottles with each leaf species within four low-order streams
      during 1st, 3rd, 7th, 22nd, 36th, 55th and 85th day of exposure. We used an
      analysis of covariance (ANCOVA) to compare differences in the percentage of AFDM
      (ash-free dry mass) and AOM (amorphous organic matter) among leaf litter species.
      To verify differences in the larvae abundance, we used a general linear model,
      and to test if there were feeding preferences for AFDM and AOM, we used the
      adapted Paloheimo selectivity index. Magnolia ovata presented a higher quantity
      of AOM followed by H. coronarium and P. arachnoideum. Pteridium arachnoideum
      showed a higher AFDM followed by H. coronarium and M. ovata. The larvae abundance
      was different among plant species and varied significantly with AFDM and AOM
      quantities. The consumption of plant tissue by shredder chironomid differed
      temporarily and among riparian species, where facultative or strict shredders
      showed strong association with different leaf litter species. The amount of AFDM
      and AOM in plant tissues explained these differences. We highlighted that
      shredder chironomids displayed an important role as co-participants in the
      decomposition process.

PMID- 29651694
TI  - Classification of ECG beats using deep belief network and active learning.
AB  - A new semi-supervised approach based on deep learning and active learning for
      classification of electrocardiogram signals (ECG) is proposed. The objective of
      the proposed work is to model a scientific method for classification of cardiac
      irregularities using electrocardiogram beats. The model follows the Association
      for the Advancement of medical instrumentation (AAMI) standards and consists of
      three phases. In phase I, feature representation of ECG is learnt using Gaussian
      Bernoulli deep belief network followed by a linear support vector machine (SVM)
      training in the consecutive phase. It yields three deep models which are based on
      AAMI-defined classes, namely N, V, S, and F. In the last phase, a query generator
      is introduced to interact with the expert to label few beats to improve accuracy
      and sensitivity. The proposed approach depicts significant improvement in
      accuracy with minimal queries posed to the expert and fast online training as
      tested on the MIT-BIH Arrhythmia Database and the MIT-BIH Supra-ventricular
      Arrhythmia Database (SVDB). With 100 queries labeled by the expert in phase III,
      the method achieves an accuracy of 99.5% in "S" versus all classifications (SVEB)
      and 99.4% accuracy in "V " versus all classifications (VEB) on MIT-BIH Arrhythmia
      Database. In a similar manner, it is attributed that an accuracy of 97.5% for
      SVEB and 98.6% for VEB on SVDB database is achieved respectively. Graphical
      Abstract Reply- Deep belief network augmented by active learning for efficient
      prediction of arrhythmia.

PMID- 29651695
TI  - Factors influencing efficacy endpoints in clinical trials for new oral medicinal
      treatments for overactive bladder: a systematic literature review and meta
      analysis.
AB  - PURPOSE: Overactive bladder (OAB) is a symptom-based disease; therefore, clinical
      trials to evaluate treatments for OAB employ a range of efficacy endpoints. Since
      factors that influence efficacy endpoints can affect trial outcomes, their
      identification could aid in the design of future OAB clinical trials. We
      investigated factors influencing different efficacy endpoints used in clinical
      trials with OAB patients and examined their characteristics to determine future
      clinical trial strategies for new medicinal treatments for OAB. METHODS: Data
      from placebo-controlled double-blind trials in patients with OAB were extracted
      via a systematic literature review. The integrated differences for efficacy
      endpoints were calculated. Heterogeneity was assessed using the Q statistic and
      I2 statistic. Factors influencing efficacy endpoints were identified through
      univariate and multivariate meta-regression analyses. RESULTS: Forty-one
      controlled trials were analyzed. Substantial heterogeneity between studies was
      observed for each efficacy endpoint (P > 0.001, I2 > 70%). We found with
      multivariate meta-regression analysis that period of recording in a bladder diary
      and year of publication were significantly likely to influence the change from
      baseline in the mean number of urgency episodes in 24 h, year of publication and
      gender were significantly likely to influence the change from baseline in the
      mean number of micturitions in 24 h, and gender was significantly likely to
      influence the change from baseline in the mean volume voided per micturition. In
      contrast, there were no factors significantly associated with change from
      baseline in the mean number of incontinence episodes in 24 h. CONCLUSIONS: We
      identified that change from baseline in the mean number of incontinence episodes
      in 24 h should serve as a relatively stable endpoint. In contrast, we identified
      factors influencing other endpoints, and the identified factors should be taken
      into account when planning and conducting future clinical trials.

PMID- 29651696
TI  - Diversity of the midstream urine microbiome in adults with chronic kidney
      disease.
AB  - PURPOSE: To examine the characteristics of the midstream urine microbiome in
      adults with stage 3-5 non-dialysis-dependent chronic kidney disease (CKD).
      METHODS: Patients with non-dialysis-dependent CKD (estimated glomerular
      filtration rate [eGFR] < 60 ml/min/1.73 m2) and diuretic use were recruited from
      outpatient nephrology clinics. Midstream voided urine specimens were collected
      using the clean-catch method. The bacterial composition was determined by
      sequencing the hypervariable (V4) region of the bacterial 16S ribosomal RNA gene.
      Extraction negative controls (no urine) were included to assess the contribution
      of extraneous DNA from possible sources of contamination. Midstream urine
      microbiome diversity was assessed with the inverse Simpson, Chao and Shannon
      indices. The diversity measures were further examined by demographic
      characteristics and by comorbidities. RESULTS: The cohort of 41 women and 36 men
      with detectable bacterial DNA in their urine samples had a mean age of 71.5 years
      (standard deviation [SD] 7.9) years (range 60-91 years). The majority were white
      (68.0%) and a substantial minority were African-American (29.3%) The mean eGFR
      was 27.2 (SD 13.6) ml/min/1.73 m2. Most men (72.2%) were circumcised and 16.6%
      reported a remote history of prostate cancer. Many midstream voided urine
      specimens were dominated (> 50% reads) by the genera Corynebacterium (n = 11),
      Staphylococcus (n = 9), Streptococcus (n = 7), Lactobacillus (n = 7), Gardnerella
      (n = 7), Prevotella (n = 4), Escherichia_Shigella (n = 3), and Enterobacteriaceae
      (n = 2); the rest lacked a dominant genus. The samples had high levels of
      diversity, as measured by the inverse Simpson [7.24 (95% CI 6.76, 7.81)], Chao
      [558.24 (95% CI 381.70, 879.35)], and Shannon indices [2.60 (95% CI 2.51, 2.69)].
      Diversity measures were generally higher in participants with urgency urinary
      incontinence and higher estimated glomerular filtration rate (eGFR). After
      controlling for demographics and diabetes status, microbiome diversity was
      significantly associated with estimated eGFR (P < 0.05). CONCLUSIONS: The
      midstream voided urine microbiome of older adults with stage 3-5 non-dialysis
      dependent CKD is diverse. Greater microbiome diversity is associated with higher
      eGFR.

PMID- 29651697
TI  - Sagittal abdominal diameter and Framingham risk score in non-dialysis chronic
      kidney disease patients.
AB  - BACKGROUND: Chronic kidney disease (CKD) is very common now and is associated
      with high overall and cardiovascular mortality. Numerous studies have reported
      that abdominal obesity is a risk factor for cardiovascular mortality. We
      investigated the link between sagittal abdominal diameter (SAD) and Framingham
      risk score in non-dialysis CKD patients. METHODS: In a cross-sectional study, we
      enrolled 307 prevalent non-dialysis CKD patients (175 males, aged 50.7 +/- 17.04
      years). SAD and Framingham risk score were measured. RESULTS: Framingham
      cardiovascular disease risk score was independently predicted by SAD (P < 0.01),
      GFR (P < 0.01) and diabetic history (P < 0.05). Adjusted R2 of the model was
      0.178. SAD could be independently predicted by BMI (P < 0.01), diabetic history
      (P < 0.01), GFR (P < 0.01) and age (P < 0.01). Adjusted R2 of the model was
      0.409. Using receiver operating characteristic (ROC) curve, a cutoff SAD value of
      16.55 cm was determined with sensitivity of 63.7%, specificity of 58.3%.
      CONCLUSION: Elevated SAD is significantly associated with increased Framingham
      risk score in non-dialysis CKD patients. SAD can be predicted by patients' BMI,
      diabetic history, renal function and age. Further investigation is needed to
      explore the potential benefits of central obesity lowering therapy in this
      patient group.

PMID- 29651698
TI  - Mitogenic activity of Artocarpus lingnanensis lectin and its apoptosis induction
      in Jurkat T cells.
AB  - Lectins are a class of carbohydrate-binding proteins or glycoproteins and used in
      the purification and characterization of glycoproteins according to their
      specificity to carbohydrates. In the present study, the mitogenic activity of
      Artocarpus lingnanensis lectin (ALL) and its apoptosis induction in Jurkat T
      cells were explored. MTT assay revealed strong mitogenic potential of ALL.
      Meanwhile, the anti-cancer activity of ALL was also explored using the human
      leukemic Jurkat T cell line. ALL exhibited strong binding affinity (97%) to the
      cell membrane, which could be effectively inhibited by N-acetyl-D-galactosaminide
      (NAD). ALL induced time- and dose-dependent growth inhibition in Jurkat T cells.
      ALL could induce morphologic change and increase the hypodiploid cell population
      with the decreased population of S and G2/M phases. The induction of
      phosphatidylserine externalization and PARP cleavage further confirmed its
      apoptosis-inducing activity due to the activation of caspase-8 and -9. The
      inhibition of caspase-9 but not caspase-8 could rescue ALL-induced apoptotic
      cells. Further studies showed that ALL enhanced the cleavage of Bid, the release
      of cytochrome C, the depolarization of mitochondria and the activation of caspase
      3. ALL downregulated the expression of Bcl-xl and Bcl-2 without impact on Bax and
      Bad. In addition, the activation of p38/JNK MAPK signaling pathways was observed
      to be a requisite for ALL apoptotic activity. In contrast, ALL could not induce
      apoptosis of normal T cells. These findings present the differential effect of
      ALL on Jurkat and normal T lymphocytes, suggesting its therapeutic value in
      leukemia.

PMID- 29651699
TI  - RETRACTED ARTICLE: Direct healthcare costs of spinal disorders in Brazil.

PMID- 29651700
TI  - Engineering Pichia pastoris for Efficient Production of a Novel Bifunctional
      Strongylocentrotus purpuratus Invertebrate-Type Lysozyme.
AB  - Lysozymes are known as ubiquitously distributed immune effectors with hydrolytic
      activity against peptidoglycan, the major bacterial cell wall polymer, to trigger
      cell lysis. In the present study, the full-length cDNA sequence of a novel sea
      urchin Strongylocentrotus purpuratus invertebrate-type lysozyme (sp-iLys) was
      synthesized according to the codon usage bias of Pichia pastoris and was cloned
      into a constitutive expression plasmid pPIC9K. The resulting plasmid, pPIC9K-sp
      iLys, was integrated into the genome of P. pastoris strain GS115. The bioactive
      recombinant sp-iLys was successfully secreted into the culture broth by positive
      transformants. The highest lytic activity of 960 U/mL of culture supernatant was
      reached in fed-batch fermentation. Using chitin affinity chromatography and gel
      filtration chromatography, recombinant sp-iLys was produced with a yield of 94.5
      mg/L and purity of > 99%. Recombinant sp-iLys reached its peak lytic activity of
      8560 U/mg at pH 6.0 and 30  degrees C and showed antimicrobial activities against
      Gram-negative bacteria (Vibrio vulnificus, Vibrio parahemolyticus, and Aeromonas
      hydrophila) and Gram-positive bacteria (Staphylococcus aureus and Bacillus
      subtilis). In addition, recombinant sp-iLys displayed isopeptidase activity which
      reached the peak at pH 7.5 and 37  degrees C with the presence of 0.05 M Na+. In
      conclusion, this report describes the heterologous expression of recombinant sp
      iLys in P. pastoris on a preparative-scale, which possesses lytic activity and
      isopeptidase activity. This suggests that sp-iLys might play an important role in
      the innate immunity of S. purpuratus.

PMID- 29651701
TI  - The preS deletion of hepatitis B virus (HBV) is associated with liver fibrosis
      progression in patients with chronic HBV infection.
AB  - BACKGROUND AND AIMS: Limited data are available regarding the association of
      hepatitis B virus (HBV) mutations with liver fibrosis in HBV infection. The study
      aimed to clarify whether HBV preS deletion mutation is associated with liver
      fibrosis progression. METHODS: A total of 469 patients were enrolled, including
      324 with chronic hepatitis B (CHB), 28 with HBV-related compensated liver
      cirrhosis (LC), and 117 with HBV-related decompensated LC. All CHB and
      compensated LC patients received liver biopsy. Fibrosis grade was assessed using
      METAVIR score. HBV preS deletion was determined by direct sequencing and verified
      by clonal sequencing. RESULTS: Overall preS deletion was detected in 12.6%
      (59/469) patients, specifically, in 7.51% (13/173), 10.60% (16/151), and 20.69%
      (30/145) of patients with no-to-mild liver fibrosis (F0-1), moderate-to-severe
      liver fibrosis (F2-3), and cirrhosis (F4), respectively (p < 0.01). Patients with
      preS-deleted HBV had lower serum HBV DNA and albumin levels compared to patients
      with wild-type HBV. The median length of preS deletion was 39-base pairs (bp) (3
      204 bp) and the deletion most frequently emerged in preS2 initial region.
      Multivariate analysis identified the preS2 deletion rather than preS1 deletion to
      be an independent risk factor of significant fibrosis, i.e., METAVIR F >= 2 (p =
      0.007). In addition, preS-deleted viral sequences were detected in the pool of
      intrahepatic HBV covalently closed circular DNA. CONCLUSIONS: HBV preS deletion
      is positively associated with liver fibrosis progression in chronic HBV-infected
      patients. HBV preS2 deletion may serve as a warning indicator for liver fibrosis
      progression.

PMID- 29651702
TI  - Tsumura-Suzuki obese diabetic mice-derived hepatic tumors closely resemble human
      hepatocellular carcinomas in metabolism-related genes expression and bile acid
      accumulation.
AB  - BACKGROUND AND AIMS: Tsumura-Suzuki obese diabetic (TSOD) is a good model of
      metabolic syndrome showing typical lesions found in nonalcoholic fatty liver
      disease and nonalcoholic steatohepatitis, and develops spontaneous hepatic tumors
      with a high frequency. Majority of the developing tumors overexpress glutamine
      synthetase (GS), which is used as a marker of hepatocellular carcinoma (HCC). The
      aim of this study is to assess the status of expression of metabolism-related
      genes and the level of bile acids in the TSOD mice-derived tumors and to
      determine the association with metabolic dysregulation between human HCC and TSOD
      mice-derived tumors. METHODS: GS-positive hepatic tumors or adjacent normal
      tissues from 71-week-old male TSOD mice were subjected to immunohistochemical
      staining, quantitative RT-PCR (qRT-PCR), quantitation of cholic acid and
      taurocholic acid. RESULTS: We found that downregulation of the rate-limiting
      enzyme for betaine synthesis (BADH), at both mRNA and protein levels in GS
      positive TSOD mice-derived tumors. Furthermore, the bile acid receptor FXR and
      the bile acid excretion pump BSEP (Abcb11) were found to be downregulated,
      whereas BAAT and Akr1c14, involved in primary bile acid synthesis and bile acid
      conjugation, were found to be upregulated at mRNA level in GS-positive TSOD mice
      derived tumors. BAAT and Akr1c14 were also overexpressed at protein levels. Total
      cholic acid was found to be increased in GS-positive TSOD mice-derived tumors.
      CONCLUSION: Our results strongly support the significance of TSOD mice as a model
      of spontaneously developing HCC.

PMID- 29651703
TI  - Spectrum of histopathological changes in patients with non-cirrhotic portal
      fibrosis.
AB  - BACKGROUND AND AIMS: Non-cirrhotic portal fibrosis (NCPF) is a clinical disorder
      characterized by features of portal hypertension in the absence of significant
      fibrosis. It is one of the commonest causes of portal hypertension in India. This
      study aimed to analyze histomorphological spectrum of NCPF in detail. METHODS AND
      RESULTS: There were 67 specimens from 66 patients which included 43 (65.2%) male
      and 23 (34.8%) female patients with a mean age of 31 years (range: 7-61 years).
      The liver function tests showed only a mild derangement. The average length of
      biopsy was 1.4 cm (median: 1.2 cm, range: 0.8-3.4 cm) and the mean number of
      portal tracts per biopsy was 11.1 (median: 10, range: 5-30). Most cases showed a
      combination of histological features; the mean number of histological features
      per biopsy was 7.4 (median: 7, range: 3-12). Obliterative portal venopathy was
      seen in 47.8% cases. Portal angiomatosis (61.2%), paraportal shunt vessels
      (61.2%), portal vein dilatation (74.6%), hypoplastic portal tracts (56.7%),
      megasinusoids (64.1%), and abnormally dilated central veins (64.1%) were other
      prevalent features. Portal/periportal fibrosis and perisinusoidal fibrosis were
      seen in 77.6% and 61.2% cases; none showed bridging fibrosis or cirrhosis. The
      median hepatic venous pressure gradient (HVPG) and liver stiffness (LS) values
      were 8 mm of Hg (range: 5-20 mm of Hg) and 9.2 kPa (range: 4.4-26.3 kPa). There
      was no correlation of HVPG or LS with either portal/periportal fibrosis or
      perisinusoidal fibrosis. CONCLUSION: Due to relatively non-specific and non
      pathognomonic nature, a combination of different histological features in the
      absence of significant fibrosis and appropriate clinico-radiological background
      is needed for diagnosing NCPF.

PMID- 29651704
TI  - HDAC9 Polymorphism Alters Blood Gene Expression in Patients with Large Vessel
      Atherosclerotic Stroke.
AB  - The histone deacetylase 9 (HDAC9) polymorphism rs2107595 is associated with an
      increased risk for large vessel atherosclerotic stroke (LVAS). In humans, there
      remains a need to better understand this HDAC9 polymorphism's contribution to
      large vessel stroke. In this pilot study, we evaluated whether the HDAC9
      polymorphism rs2107595 is associated with differences in leukocyte gene
      expression in patients with LVAS. HDAC9 SNP rs2107595 was genotyped in 155
      patients (43 LVAS and 112 vascular risk factor controls). RNA isolated from blood
      was processed on whole genome microarrays. Gene expression was compared between
      HDAC9 risk allele-positive and risk allele-negative LVAS patients and controls.
      Functional analysis identified canonical pathways and molecular functions
      associated with rs2107595 in LVAS. In HDAC9 SNP rs2107595 risk allele-positive
      LVAS patients, there were 155 genes differentially expressed compared to risk
      allele-negative patients (fold change > |1.2|, p < 0.05). The 155 genes separated
      the risk allele-positive and risk allele-negative LVAS patients on a principal
      component analysis. Pathways associated with HDAC9 risk allele-positive status
      involved IL-6 signaling, cholesterol efflux, and platelet aggregation. These
      preliminary data suggest an association with the HDAC9 rs2107595 risk allele and
      peripheral immune, lipid, and clotting systems in LVAS. Further study is required
      to evaluate whether these differences are related to large vessel atherosclerosis
      and stroke risk.

PMID- 29651706
TI  - A randomized trial of three lubrication strategies on sore throat after insertion
      of the LMA(r) ClassicTM supraglottic airway.

PMID- 29651705
TI  - Rat Cerebrospinal Fluid Treatment Method through Cisterna Cerebellomedullaris
      Injection.
AB  - Drugs that lack the ability to cross the blood-brain barrier (BBB) need to be
      placed directly into the central nervous system. Our laboratory studies the
      involvement of the glutamatergic system in the aggressiveness of glioma, and some
      ligands of glutamate receptors cannot permeate the BBB. Here, glioma-implanted
      rats were treated by a technique that delivers ligands directly into the
      cerebrospinal fluid by puncture into the cisterna cerebellomedullaris. Rats were
      anesthetized and fixed in a rodent stereotactic device. The head was gently
      tilted downwards at an angle that allowed exposure of the cisterna. Injection
      into the cisterna was done freehand using a gingival needle coupled to a
      microsyringe. The efficiency of intracisternal injection was demonstrated using a
      methylene blue solution. This type of injection is adaptable for any rodent model
      using small volumes of a variety of other drugs, and is an interesting method for
      neuroscience studies.

PMID- 29651707
TI  - [Radiochemotherapy for invasive bladder cancer : An update].
AB  - BACKGROUND: The standard treatment for muscle-invasive bladder cancer is radical
      cystectomy with pelvic lymphadenectomy. Primary organ-preservation by means of
      multimodal therapy, however, can be a viable alternative to radical surgery.
      OBJECTIVES: The concept and results of multimodal therapy, consisting of initial
      transurethral resection of the bladder tumor (TUR-B), followed by simultaneous
      radiochemotherapy (RCT), are presented. MATERIALS AND METHODS: Evaluation of
      retrospective cohorts and prospective therapy optimization studies on organ
      preservation treatment regimens. Comparative meta-analyses comparing cystectomy
      with multimodal treatment are presented. RESULTS: Complete TUR-B, including
      bladder mapping and tumor biopsy, should precede simultaneous RCT.
      Radiosensitization should be cisplatin-based or consist of a combination of 5
      fluorouracil and mitomycin C. Complete response rates after TUR-B plus RCT are
      generated in 60-90% of patients along with 5-year survival rates of 40-75% and
      preservation of the bladder in approximately 80% of surviving patients.
      CONCLUSIONS: Multimodal therapy by means of TUR-B followed by simultaneous RCT is
      a viable alternative to radical cystectomy for patients with muscle-invasive
      urinary bladder carcinoma. Patients with early tumors (cT2/3N0) are particularly
      suitable in whom initial TUR-B leads to complete tumor resection (R0).

PMID- 29651708
TI  - [En bloc resection and vaporization techniques for the treatment of bladder
      cancer].
AB  - BACKGROUND: Modifications in resection techniques may overcome obvious
      limitations of conventionally performed transurethral resection (e. g., tumor
      fragmentation) of bladder tumors or provide an easier patient treatment algorithm
      (e. g., tumor vaporization). OBJECTIVES: The present review article summarizes
      the current literature in terms of en bloc resection techniques,
      histopathological quality, complication rates, and oncological outcomes.
      MATERIALS AND METHODS: A separate data search was performed for en bloc resection
      (ERBT, n = 27) and vaporization (n = 15) of bladder tumors. RESULTS: In most
      cases, ERBT is performed in a circumferential fashion. Alternatively, ERBT may be
      performed by undermining the tumor base via antegrade application of short energy
      impulses. Based on high rates of detrusor in specimens of ERBT (90-100%), a
      better histopathological quality is assumed. Significant differences in
      perioperative complication rates have not been observed, although obturator-nerve
      based bladder perforations are not seen when laser energy is used. There is a
      nonstatistically significant trend towards lower recurrence rates in ERBT groups.
      Tumor vaporization may provide a less invasive technique for older patients with
      recurrences of low-risk bladder cancer. It can be performed in an outpatient
      setting. CONCLUSIONS: ERBT may provide better histopathological quality. Tumor
      vaporization is performed in health care systems where reimbursement is adequate.

PMID- 29651709
TI  - [Cannabinoid therapy in practice].
AB  - BACKGROUND: In recent years, the media and scientists have shown increased
      interest in cannabis-based drugs. OBJECTIVES: Background information about
      cannabis-based drugs and their mechanism of action as well as discussion of
      possible applications as supportive therapy or in palliative medicine,
      respectively, are presented. MATERIALS AND METHODS: The recent literature was
      examined and evaluated. RESULTS: In many medical fields, we do not have
      sufficient evidence for the efficacy of cannabinoids. In German pharmaceutical
      legislation, the use of nabiximols for the treatment of intermediate to severe,
      therapy-resistant spasticity in multiple sclerosis is the only approved
      indication for cannabis-based drugs. Furthermore, in view of the current evidence
      cannabinoids, combined with established treatments and as part of an individual
      therapeutic attempt, can be used for neuropathic pain, cancer-associated pain and
      human immunodeficiency virus (HIV)-related cachexia. CONCLUSIONS: In most cases,
      today's assessment of cannabinoids relies on studies that are classified as low
      evidence. Therefore, further studies which involve more participants and evaluate
      long-term effects are needed.

PMID- 29651710
TI  - [Strategies to reduce patient loss during the follow-up period of randomized
      trials].

PMID- 29651711
TI  - Baclofen to Prevent Relapse in Gamma-Hydroxybutyrate (GHB)-Dependent Patients: A
      Multicentre, Open-Label, Non-Randomized, Controlled Trial.
AB  - BACKGROUND: Gamma-hydroxybutyrate (GHB) dependence is associated with a severe,
      potentially lethal, withdrawal syndrome and relapse rates as high as 60% within 3
      months of detoxification. Baclofen has been shown to decrease self-administration
      of GHB in mice and reduce relapse in a case series of GHB-dependent patients.
      Controlled studies on the effectiveness of baclofen to prevent relapse in GHB
      dependent patients are lacking. AIM: The aim of this study was to assess
      effectiveness of baclofen in preventing relapse in GHB-dependent patients.
      METHODS: This was an out-patient, multicentre, open-label, non-randomized,
      controlled trial in GHB-dependent patients (n = 107) in the Netherlands.
      Treatment as usual (TAU, n = 70) was compared with TAU plus baclofen 45-60 mg/day
      for 3 months (n = 37). Outcome measures were rates of lapse (any use) and relapse
      (using GHB on average once a week or more), based on self-report. Side effects
      were monitored with a baclofen side-effects questionnaire. Treatment groups were
      compared using Chi square analyses, with both per-protocol (PP) and intention-to
      treat (ITT) analyses. RESULTS: GHB-dependent patients treated with baclofen after
      detoxification showed no reduced lapse rates, but reduced relapse and dropout
      rates, compared with patients receiving TAU only (24 vs 50%). While both ITT and
      PP analyses revealed similar results, the effectiveness of baclofen prescribed PP
      was slightly higher than in ITT analysis. Patients reported overall limited side
      effects, with the most frequently reported being feeling tired (28%), sleepiness
      (14%) and feeling depressed (14%). No serious adverse events were reported.
      CONCLUSIONS: This study showed potential effectiveness of baclofen in preventing
      relapse in patients with GHB dependence after detoxification. Though promising,
      future studies with longer follow-up and a randomized double-blind design should
      confirm these findings before recommendations for clinical practice can be made.
      CLINICAL TRIAL REGISTRATION: Netherlands Trial Register with number NTR4528.

PMID- 29651712
TI  - Prognostic impact of nodal relapse in definitive prostate-only irradiation.
AB  - BACKGROUND: Whole pelvic irradiation in prostate cancer patients might prevent
      metastatic spread of cancer cells through lymphatic drainages in patients
      eligible for definitive radiotherapy, but its use has declined in the last
      decades in favor of prostate-only irradiation (POI). The aim of our study is to
      assess the incidence of pelvic lymph nodal relapse and outcome in prostate cancer
      patients receiving POI. MATERIALS AND METHODS: Data from 207 consecutive patients
      were collected. Clinical and treatment variables were collected. Biochemical
      relapse-free survival (BRFS), pelvic nodal relapse-free survival (PNRFS), distant
      metastasis-free survival (DMFS), disease-specific survival (DSS) and overall
      survival (OS) were calculated; analysis of prognostic variables was performed.
      RESULTS: Five-year BRFS, PNRFS, DMFS, DSS and OS were, respectively, 90, 98, 96,
      97 and 91%. On multivariate analysis, independent negative predictors of BRFS
      were Gleason score >= 7 (HR: 3.25) and PSA nadir >= 0.08 (HR: 4.86). Pelvic nodal
      relapse was not correlated to impaired outcome. CONCLUSIONS: Lymph nodal pelvic
      relapse occurs in 2% of patients at 5 years and does not correlate with impaired
      outcome, suggesting the lack of theoretical benefit of a prophylactic nodal
      irradiation. Tumor biology and response to treatment are the main determinants of
      outcome.

PMID- 29651713
TI  - Correlation of listhesis on upright radiographs and central lumbar spinal canal
      stenosis on supine MRI: is it possible to predict lumbar spinal canal stenosis?
AB  - OBJECTIVE: To investigate whether upright radiographs can predict lumbar spinal
      canal stenosis using supine lumbar magnetic resonance imaging (MRI) and to
      investigate the detection performance for spondylolisthesis on upright
      radiographs compared with supine MRI in patients with suspected lumbar spinal
      canal stenosis (LSS). MATERIALS AND METHODS: In this retrospective study,
      conventional radiographs and MR images of 143 consecutive patients with suspected
      LSS (75 female, mean age 72 years) were evaluated. The presence and extent of
      listhesis (median +/- interquartile range) were assessed on upright radiographs
      and supine MRI of L4/5. In addition, the grade of central spinal stenosis of the
      same level was evaluated on MRI according to the classification of Schizas and
      correlated with the severity/grading of anterolisthesis on radiographs. RESULTS:
      Anterolisthesis was detected in significantly more patients on radiographs (n =
      54; 38%) compared with MRI (n = 28; 20%), p < 0.001. Pairwise comparison
      demonstrated a significantly larger extent of anterolisthesis on radiographs (9
      +/- 5 mm) compared with MRI (5 +/- 3 mm), p < 0.001. A positive correlation was
      found regarding the extent of anterolisthesis measured on radiographs and the
      grade of stenosis on MRI (r = 0.563, p < 0.001). Applying a cutoff value of >=5
      mm anterolisthesis on radiographs results in a specificity of 90% and a positive
      predictive value of 78% for the detection of patients with LSS, as defined by the
      Schizas classification. CONCLUSION: Upright radiographs demonstrated more and
      larger extents of anterolisthesis compared with supine MRI. In addition, in
      patients with suspected LSS, the extent of anterolisthesis on radiographs
      (particularly >=5 mm) is indicative of LSS and warrants lumbar spine MRI.

PMID- 29651714
TI  - Learning-based endovascular navigation through the use of non-rigid registration
      for collaborative robotic catheterization.
AB  - PURPOSE: Endovascular intervention is limited by two-dimensional intraoperative
      imaging and prolonged procedure times in the presence of complex anatomies.
      Robotic catheter technology could offer benefits such as reduced radiation
      exposure to the clinician and improved intravascular navigation. Incorporating
      three-dimensional preoperative imaging into a semiautonomous robotic
      catheterization platform has the potential for safer and more precise navigation.
      This paper discusses a semiautonomous robotic catheter platform based on previous
      work (Rafii-Tari et al., in: MICCAI2013, pp 369-377. https://doi.org/10.1007/978
      3-642-40763-5_46 , 2013) by proposing a method to address anatomical variability
      among aortic arches. It incorporates anatomical information in the process of
      catheter trajectories optimization, hence can adapt to the scale and orientation
      differences among patient-specific anatomies. METHODS: Statistical modeling is
      implemented to encode the catheter motions of both proximal and distal sites
      based on cannulation data obtained from a single phantom by an expert operator.
      Non-rigid registration is applied to obtain a warping function to map catheter
      tip trajectories into other anatomically similar but shape/scale/orientation
      different models. The remapped trajectories were used to generate robot
      trajectories to conduct a collaborative cannulation task under flow simulations.
      Cross-validations were performed to test the performance of the non-rigid
      registration. Success rates of the cannulation task executed by the robotic
      platform were measured. The quality of the catheterization was also assessed
      using performance metrics for manual and robotic approaches. Furthermore, the
      contact forces between the instruments and the phantoms were measured and
      compared for both approaches. RESULTS: The success rate for semiautomatic
      cannulation is 98.1% under dry simulation and 94.4% under continuous flow
      simulation. The proposed robotic approach achieved smoother catheter paths than
      manual approach. The mean contact forces have been reduced by 33.3% with the
      robotic approach, and 70.6% less STDEV forces were observed with the robot.
      CONCLUSIONS: This work provides insights into catheter task planning and an
      improved design of hands-on ergonomic catheter navigation robots.

PMID- 29651715
TI  - Can tumor coverage evaluated 24 h post-radiofrequency ablation predict local
      tumor progression of liver metastases?
AB  - PURPOSE: To assess the predictive value for local tumor progression (LTP) of
      geometrical tumor coverage using the contrast-enhanced (ce-)CT images acquired
      before and within 24 h after radiofrequency (RF) ablation. METHODS: Twenty
      patients (6 male and 14 female, median age 62 years) with 45 focal hypovascular
      liver metastases (16 colorectal carcinoma, 3 melanoma and 1 breast carcinoma)
      underwent RF ablation under CT-guidance and received a ce-PET/CT scan within 24 h
      post-procedure. Pre- and post-ablation ce-CT-images were aligned using an
      interactive procedure and used to verify the tumor coverage of the RF ablation.
      Results were correlated to LTP as recorded during follow-up performed every 2-3
      months after the intervention (mean follow-up of 110 weeks) and compared to
      standard reading performed by three readers of the ce-CT images. RESULTS: Eleven
      tumors (25%) showed LTP during the follow-up period. One lesion, which did not
      show LTP, was excluded from analysis due to the poor quality of the alignment.
      For the remaining, 29 (66%) tumors were completely covered by the ablation zone,
      9 (20%) were not, and for 6 (14%) tumors the edges coincided with the edge of the
      ablation zone. The sensitivity, specificity, PPV and NPV for LTP of having
      incomplete tumor coverage or no apparent ablative margin versus standard reading
      of ce-CT were 100, 88, 73 and 100% versus 42, 88, 58 and 82%, respectively.
      CONCLUSIONS: Verifying the tumor coverage of liver metastases by an ablation zone
      through alignment of pre- and early post-ablation ce-CT images has a high
      predictive value for LTP.

PMID- 29651716
TI  - Super Secondary Structure Consisting of a Polyproline II Helix and a beta-Turn in
      Leucine Rich Repeats in Bacterial Type III Secretion System Effectors.
AB  - Leucine rich repeats (LRRs) are present in over 100,000 proteins from viruses to
      eukaryotes. The LRRs are 20-30 residues long and occur in tandem. LRRs form
      parallel stacks of short beta-strands and then assume a super helical arrangement
      called a solenoid structure. Individual LRRs are separated into highly conserved
      segment (HCS) with the consensus of LxxLxLxxNxL and variable segment (VS). Eight
      classes have been recognized. Bacterial LRRs are short and characterized by two
      prolines in the VS; the consensus is xxLPxLPxx with Nine residues (N-subtype) and
      xxLPxxLPxx with Ten residues (T-subtype). Bacterial LRRs are contained in type
      III secretion system effectors such as YopM, IpaH3/9.8, SspH1/2, and SlrP from
      bacteria. Some LRRs in decorin, fribromodulin, TLR8/9, and FLRT2/3 from
      vertebrate also contain the motifs. In order to understand structural features of
      bacterial LRRs, we performed both secondary structures assignments using four
      programs-DSSP-PPII, PROSS, SEGNO, and XTLSSTR-and HELFIT analyses (calculating
      helix axis, pitch, radius, residues per turn, and handedness), based on the
      atomic coordinates of their crystal structures. The N-subtype VS adopts a left
      handed polyproline II helix (PPII) with four, five or six residues and a type I
      beta-turn at the C-terminal side. Thus, the N-subtype is characterized by a super
      secondary structure consisting of a PPII and a beta-turn. In contrast, the T
      subtype VS prefers two separate PPIIs with two or three and two residues. The
      HELFIT analysis indicates that the type I beta-turn is a right handed helix. The
      HELFIT analysis determines three unit vectors of the helix axes of PPII (P), beta
      turn (B), and LRR domain (A). Three structural parameters using these three helix
      axes are suggested to characterize the super secondary structure and the LRR
      domain.

PMID- 29651717
TI  - Alcohol Metabolic Inefficiency: Structural Characterization of Polymorphism
      Induced ALDH2 Dysfunctionality and Allosteric Site Identification for Design of
      Potential Wildtype Reactivators.
AB  - Liver mitochondrial aldehyde dehydrogenase 2 (ALDH2) enzyme is responsible for
      the rapid conversion of acetaldehyde to acetic acid. ALDH2 (E487K) polymorphism
      results in an inactive allele (ALDH2*2) which cause dysfunctional acetaldehyde
      metabolism. The 3D structure of an enzyme is crucial to its functionality and a
      disruption in its structural integrity could result in its metabolic inefficiency
      and dysfunctionality. Allosteric targeting of polymorphs could facilitate the
      restoration of wildtype functionalities in ALDH2 polymorphs and serve as an
      advancement in the treatment of associated diseases. Therefore, structural
      insights into ALDH2*2 polymorph could reveal the varying degree of alterations
      which occur at its critical domains and accounts for enzymatic dysfunctionality.
      In this study, we report the structural characterization of ALDH2*2 polymorph and
      its critical domains using computational tools. Our findings revealed that the
      polymorph exhibited significant alterations in stability and flexibility at the
      catalytic and co-enzyme-binding domain. Moreover, there was an increase in the
      solvent-exposed surface residues and this indicates structural perturbations.
      Analysis of the interaction network at ALDH2*2 catalytic domain revealed residual
      displacement and interaction loss when compared to the wildtype thereby providing
      insight into the catalytic inefficiency of the polymorph. Interestingly,
      perturbations induced by ALDH2 polymorphism involves the re-orientation of
      surface residues, which resulted in the formation of surface exposed pockets.
      These identified pockets could be potential sites for allosteric targeting. The
      findings from this study will aid the design of novel site-specific small
      molecule reactivators with the propensity of restoring wildtype activities for
      treatment of polymorphic ALDH2 related diseases.

PMID- 29651719
TI  - Epilepsy in popular Medicine from the Classic Age to the Modern Age: a study on
      elk hoof as an original treatment.
AB  - European people believed that epilepsy was both a sacred and demoniac disease in
      the pre- and post-Hippocratic Age, and this belief continued into the Christian
      era. Epilepsy was wrapped in mystery. The present work shows an epileptic
      treatment using elk (Alces alces) hoof, which was better known among Northern
      European people, and explains its historical and popular origins that lead to its
      importance and success within the Official Medicine in the sixteenth and
      seventeenth centuries until its gradual decline as a specific treatment in the
      subsequent centuries. We study authors from both Antiquity and the Modern Age.
      The present work concludes by highlighting the relationship between epilepsy and
      its magic-religious inheritance. It could be considered a valid example showing
      how a popular treatment can earn honors in the Official Pharmacopoeia, but later
      be excluded.

PMID- 29651718
TI  - The clinicopathological and prognostic significance of TP53 alteration in K27M
      mutated gliomas: an individual-participant data meta-analysis.
AB  - This study aimed to investigate the impact of TP53 alteration on survival and
      clinicopathological features of glioma patients with H3K27M mutations. An
      individual-participant-data (IPD) meta-analysis was performed to investigate the
      impact of TP53 alteration on survival and clinicopathological features of
      patients with H3K27M mutations. Three hundred thirty-one individual records from
      12 eligible glioma studies involving the H3K27M mutation were finally included in
      our meta-analysis, and a pooled hazard ratio (HR) of 1.53 (95%CI, 1.10-2.11; P =
      0.01) indicated that TP53 alterations were associated with a shorter overall
      survival. The pooled odds ratios (ORs) indicated that TP53 alterations were
      significantly associated with the age at diagnosis >= 7 years (OR = 1.97, 95%CI =
      1.15-3.38, P = 0.01), the status of histone H3.3 mutations (OR = 9.15, 95%CI =
      4.18-20.06, P < 0.00001), and high WHO grade histology (III + IV) (OR = 2.70,
      95%CI = 1.33-5.48, P = 0.006). However, no association was found between TP53
      alterations and gender or tumor location. This IPD meta-analysis suggests that
      TP53 alteration is a valuable predictor for the prognosis of patients with H3K27M
      mutated gliomas. TP53 alteration may be used for identifying a subset of patients
      who potentially benefit from targeted reactivation of TP53 activity.

PMID- 29651720
TI  - Biomarkers study in atypical dementia: proof of a diagnostic work-up.
AB  - BACKGROUND: An early differentiation between Alzheimer's Disease (AD) and other
      dementias is crucial for an adequate patients' management, albeit it may result
      difficult for the occurrence of "atypical presentations." Current diagnostic
      criteria recognize the importance of biomarkers for AD diagnosis, but still an
      optimal diagnostic work-up isn't available. OBJECTIVE: Evaluate the utility and
      reproducibility of biomarkers and propose an "optimal" diagnostic work-up in
      atypical dementia. METHODS: (1) a retrospective selection of "atypical dementia
      cases"; (2) a repetition of diagnostic assessment by two neurologists following
      two different diagnostic work-ups, each consisting of multiple steps; (3) a
      comparison between diagnostic accuracy and confidence reached at each step by
      both neurologists and evaluation of the inter-rater agreement. RESULTS: In AD,
      regardless of the undertaken diagnostic work-up, a significant gain in accuracy
      was reached by both neurologists after the second step, whereas in frontotemporal
      dementia (FTD), adding subsequent steps was not always sufficient to increase
      significantly the baseline accuracy. A relevant increment in diagnostic
      confidence was detectable after studying pathophysiological markers in AD, and
      after assessing brain metabolism in FTD. The inter-rater agreement was higher at
      the second step for the AD group when the pathophysiological markers were
      available and for the FTD group when the results of FDG-PET were accessible.
      CONCLUSIONS: In atypical cases of dementia, biomarkers significantly raise
      diagnostic accuracy, confidence, and agreement. This study introduces a proof of
      diagnostic work-up that combines imaging and CSF biomarkers and suggests distinct
      ways to proceed on the basis of a greater diagnostic likelihood.

PMID- 29651722
TI  - Correction to: Ultrasound enhanced activation of peroxydisulfate by activated
      carbon fiber for decolorization of azo dye.
AB  - The correct name of the 5th Author is Jiabin Chen.

PMID- 29651721
TI  - The correlation between growth hormone receptor (GHR) polymorphism and
      obstructive sleep apnea syndrome among the Han and Hani population in China.
AB  - Obstructive sleep apnea syndrome (OSAS) is a common health problem that is
      associated with abnormality in craniofacial morphology. The growth hormone
      receptor (GHR) belongs to the cytokine receptor superfamily and mediates the
      majority of growth hormone signaling, which, among other functions, determines
      mandibular growth and development. The aim of this study was to determine if
      correlations exist between single nucleotide polymorphisms (SNPs) in the GHR gene
      and OSAS in the Han or Hani ethnic groups in China. A total of 274 Han subjects
      (106 with OSAS and 168 without OSAS) and a total of 270 Hani subjects (64 with
      OSAS and 206 without OSAS) were enrolled in our study. Genomic DNA was extracted
      from peripheral blood obtained from all subjects. Genotyping was undertaken for
      eight SNPs in the GHR gene (rs3756416, rs7727047, rs2910875, rs12153009,
      rs2972781, rs12518414, rs4410646, and rs6451620) using PCR amplification and
      Sanger sequencing. The genotype frequency of rs12518414 was associated with OSAS
      in both the Han and Hani groups, and the A allele frequency was remarkably lower
      in Hani OSAS patients compared with Hani controls (16.7 vs 29.9%). In addition,
      the G allele frequency of the rs3756416 SNP was significantly lower in OSAS
      patients compared with normal controls in the Hani ethnic group (12.5 vs 24.6%).
      In a comparison between ethnic groups, genotype frequencies of four SNPs
      (rs2972781, rs6451620, rs12518414, and rs7727047) differed between Han and Hani
      OSAS patients, with the A allele frequency of the rs12518414 and G allele
      frequency of the rs7727047 were significantly higher in the Han OSAS patients. In
      conclusion, significant associations were detected between some SNPs in the GHR
      gene and OSAS occurrence while others appeared to be ethnicity-dependent.

PMID- 29651723
TI  - Sulfur extraction from liquid fuels using trihexyl(tetradecyl)phosphonium
      tetrafluoroborate: as promising solvent.
AB  - Sulfur extraction from fuel is essential to be done for environmental and
      industrial point of view. Extractive desulfurization (EDS) is one of the most
      promising techniques in order to achieve legislative sulfur content requirements.
      Among numerous extractants and solvents, ionic liquids (ILs) are more capable due
      to their desirable green solvent properties. This work demonstrated that
      trihexyl(tetradecyl)phosphonium tetrafluoroborate ([THTDP]BF4) was synthesized,
      characterized, and employed as extraction solvent for extraction of
      dibenzothiophene (DBT), thiophene, benzothiophene, and other alkyl-substituted
      derivatives of sulfur from liquid fuel. Molecular confirmation and purity of
      synthesized ([THTDP]BF4) were analyzed with FTIR, Raman, NMR, EPR, UV, TG/DSC,
      and XRD analyses. Also, physical properties of ([THTDP]BF4) were carried out. The
      effects of extraction time, temperature, sulfur compounds, ultra-sonication, and
      ([THTDP]BF4) recycling/regeneration on DBT removal from liquid fuel were also
      examined. DBT removal in n-dodecane was 92.6% using EDS with mass ratio (1:1) in
      30 min at 30  degrees C under the mild reaction conditions. ([THTDP]BF4) could be
      reused up to ten cycles for sulfur extraction and regenerated for few more cycles
      with good DBT removal ability. Also, the sulfur extraction from real fuels and
      multistage extraction performance were tested. The experimental data and results
      provided in this article discover the remarkable understandings of
      tetrafluoroborate-based phosphonium ionic liquids as promising solvent for EDS.

PMID- 29651724
TI  - Serum folate and cobalamin levels and urinary dimethylarsinic acid in US children
      and adults.
AB  - Nutritional status could affect arsenic metabolism and toxicity in the general
      population chronically exposed to low levels of inorganic arsenic. In this study,
      we examined the association of serum folate and cobalamin with urinary
      concentrations of dimethylarsinic acid (DMA), the most abundant metabolite of
      inorganic arsenic measured in urine, in children and adults who participated in
      the 2003-2006 US National Health and Nutrition Examination Surveys. A total of
      1161 children (aged 6-19 years) and 1938 adults (aged 20-85 years) were analyzed
      for the association using multivariate general linear models, adjusting for
      potential confounders. We observed a positive association between serum levels of
      folate and cobalamin and creatinine-corrected urinary concentrations of DMA in
      both children and adults. Furthermore, serum levels of folate and cobalamin were
      inversely associated with homocysteine (Hcy). These results suggest that dietary
      intake of folate and cobalamin may exhibit protective functions against arsenic
      toxicity by increasing arsenic metabolism to the less toxic metabolite DMA and
      decreasing serum levels of Hcy.

PMID- 29651725
TI  - The heterogeneous effects of urbanization and income inequality on CO2 emissions
      in BRICS economies: evidence from panel quantile regression.
AB  - This paper empirically examines the effects of urbanization and income inequality
      on CO2 emissions in the BRICS economies (i.e., Brazil, Russia, India, China, and
      South Africa) during the periods 1994-2013. The method we used is the panel
      quantile regression, which takes into account the unobserved individual
      heterogeneity and distributional heterogeneity. Our empirical results indicate
      that urbanization has a significant and negative impact on carbon emissions,
      except in the 80th, 90th, and 95th quantiles. We also quantitatively investigate
      the direct and indirect effect of urbanization on carbon emissions, and the
      results show that we may underestimate urbanization's effect on carbon emissions
      if we ignore its indirect effect. In addition, in middle- and high-emission
      countries, income inequality has a significant and positive impact on carbon
      emissions. The results of our study indicate that in the BRICS economies, there
      is an inverted U-shaped environmental Kuznets curve (EKC) between the GDP per
      capita and carbon emissions. The conclusions of this study have important policy
      implications for policymakers. Policymakers should try to narrow the income gap
      between the rich and the poor to improve environmental quality; the BRICS
      economies can speed up urbanization to reduce carbon emissions, but they must
      improve energy efficiency and use clean energy to the greatest extent in the
      process.

PMID- 29651726
TI  - Biosorption of strontium ions from simulated high-level liquid waste by living
      Saccharomyces cerevisiae.
AB  - In this study, the Saccharomyces cerevisiae (S. cerevisiae) was modified by gamma
      ray. The RNA-seq results reflect that the high gamma-ray energies could change
      some gene fragments, such as deletion, recombination, and mutation. The
      biosorption of strontium ions (Sr2+) to different types of S. cerevisiae (S.
      cerevisiae (K-0), modified S. cerevisiae (Y-7), and non-living S. cerevisiae (H
      K)) from the simulated high-level liquid waste (S-HLLW) was assessed at different
      experimental conditions. The sorption experimental results show that, under an
      appropriate condition, gamma-ray radiation can enhance its biosorption capacity
      slightly of Sr2+ to S. cerevisiae. The maximum metal uptake and efficiency of Y-7
      under S-HLLW were 11.656 mg g-1 and 37.91% at 32 h (wet weight), respectively.
      They decreased to 9.46 mg g-1 and 30.76% under radiation conditions. SEM-EDX and
      TEM analysis indicates that Sr2+ was adsorbed both on the cellular surface and
      the inner parts of the cells. Our experimental results fit well to the Langmuir
      and Freundlich model isotherms (r2 > 0.94), and the maximum biosorption capacity
      values reached qmax > 24.74 mg g-1 at 32  degrees C. Negative values of DeltaG0
      and positive values of DeltaH0 were observed, indicating the spontaneous and
      endothermic nature of Sr2+ biosorption on modified S. cerevisiae. The biosorption
      kinetics follow a pseudo-second-order equation at 32  degrees C (r2 > 0.94). The
      desorption efficiency of Sr2+ adsorbed onto Y-7 was 7.65 +/- 0.52%, 76.51 +/-
      2.13%, and 65.62 +/- 2.42% by deionized water, 1 M HCl, and 0.1 M EDTA-Na,
      respectively. However, they were lower than H-K (18.82, 83.32, and 73.32%). Our
      findings demonstrate that living S. cerevisiae (Y-7) is a promising sorbent
      material for the treatment of radioactive process streams.

PMID- 29651727
TI  - Biological control of Meloidogyne javanica on tomato with Dazitol(r) and soil
      solarization.
AB  - Pot and greenhouse trials were conducted for the management of root-knot
      nematode, Meloidogyne javanica, infestation in tomato. Growth parameters, gall
      index, soil, and root nematode populations were measured to assess the effect of
      a novel bio-pesticide (Dazitol(r)), made from mustard oil and oleoresin of
      Capsicum, on plant growth and nematode reproduction. Data generated within the
      pot experiment showed that the tested bio-pesticide did not improve plant growth,
      but it reduced significantly root-knot nematode damage resulting in a decrease in
      gall index and root (91%) and soil (62%) population of M. javanica compared with
      untreated plants. The greenhouse experiment showed that Mocap(r) and Dazitol(r)
      decreased nematode incidence significantly (P < 0.05) on tomato. The result of
      this study suggested that the best nematode control was obtained by combining
      soil solarization with chemical or botanical nematicides as an integrated pest
      management approach.

PMID- 29651728
TI  - The ecological competition and grazing reverse the effects of sulfamethoxazole on
      plankton: a case study on characterizing community-level effect.
AB  - The toxic effects of sulfamethoxazole (SMX) on densities of two algae, Platymonas
      helgolandica var. tsingtaoensis, Isochrysis galbana, and of a rotifer, Brachionus
      plicatilis, were tested by the population and community experiments. Two
      endpoints, the carrying capacity and the densities array of community in steady
      state (DACS), were used to characterize the toxic effects at a population level
      and a community one, respectively. The results showed that the carrying capacity
      of P. helgolandica var. tsingtaoensis and B. plicatilis did not decline
      significantly in population test when the concentration of SMX was lower than 6.0
      mg L-1 and 12.0 mg L-1, respectively. However, I. galbana was sensitive to SMX
      and had presented toxic effect at 3.0 mg L-1. By extrapolation of toxic effect at
      a population level to a community one, a derived community-NOEC was 3.0 mg L-1,
      representing an inference from data of toxic effects at population level. In
      community experiment, when the customized community was in steady state, the
      density of I. galbana increased as a whole with SMX concentration in the range of
      tested concentration (0-144 mg L-1), while that of P. helgolandica var.
      tsingtaoensis assumed the trend of a reversed "v" in this range. Only the density
      of B. plicatilis decreased with SMX concentration. With the DACS as endpoint, a
      NOEC for the customized community was determined to be 6.0 mg L-1. This indicates
      that interspecific interactions can reverse the toxic effects of SMX on
      phytoplankton. The DACS was reliable and stable, serving as the endpoints in
      assessment of the effects of the pollutants on the ecosystems.

PMID- 29651729
TI  - Stochastic convergence of renewable energy consumption in OECD countries: a
      fractional integration approach.
AB  - In this article, we have examined the hypothesis of convergence of renewable
      energy consumption in 27 OECD countries. However, instead of relying on classical
      techniques, which are based on the dichotomy between stationarity I(0) and
      nonstationarity I(1), we consider a more flexible approach based on fractional
      integration. We employ both parametric and semiparametric techniques. Using
      parametric methods, evidence of convergence is found in the cases of Mexico,
      Switzerland and Sweden along with the USA, Portugal, the Czech Republic, South
      Korea and Spain, and employing semiparametric approaches, we found evidence of
      convergence in all these eight countries along with Australia, France, Japan,
      Greece, Italy and Poland. For the remaining 13 countries, even though the orders
      of integration of the series are smaller than one in all cases except Germany,
      the confidence intervals are so wide that we cannot reject the hypothesis of unit
      roots thus not finding support for the hypothesis of convergence.

PMID- 29651730
TI  - Reductive decolorization of azo dyes via in situ generation of green tea extract
      iron chelate.
AB  - In this study, rapid decolorization of azo dyes was achieved by in situ-generated
      green tea extract-iron (GTE-Fe) chelate for the first time. When changing
      reaction conditions from the aerobic condition to the anaerobic condition, the
      decolorization efficiencies of two azo dyes, i.e., acid orange 7 (AO7) and acid
      black 1 (AB1), increased from 46.38 and 83.17 to 90.13 and 95.37%, respectively.
      The recalcitrant AO7 was then selected as the targeting pollutant in subsequent
      optimization and mechanism studies. Experimental evidences showed that the
      initial concentrations of AO7, Fe(III), and GTE are the key factors to optimize
      the decolorization efficiency. Further characterization studies by spectroscopic
      analysis, including FESEM, FTIR, and XPS, suggested that the major mechanism of
      AO7 decolorization is the nucleophilic attack of the oxygen in green tea
      polyphenols (GTP), and this attack could be facilitated by the organometal
      chelation. This study provided an efficient and environmental friendly strategy
      to decolorize azo dyes via in situ generation of the GTE-Fe chelate, as well as
      its mechanistic insights, shedding lights on in situ remediation of azo dye
      pollution. Graphical abstract ?.

PMID- 29651732
TI  - Maternal Cadmium Levels During Pregnancy and the Relationship with Preeclampsia
      and Fetal Biometric Parameters.
AB  - Preeclampsia, which is caused by multiple factors, still remains one of the most
      serious complications of pregnancy. This study was designed to determine cadmium
      levels in women with preeclampsia compared to those of normotensive women. In
      this case-control study, maternal blood, umbilical cord blood, and placental
      cadmium levels were measured by an inductively coupled plasma mass spectrometry
      system in 51 women presenting consecutively with preeclampsia and 51 normotensive
      pregnant women. Groups were matched for maternal age, parity, and gestational
      age. Birth outcomes were recorded, such as gestational age at delivery, birth
      weight, and Apgar score. Median (interquartile range [IQR]) blood cadmium
      concentration was 1.21 MUg/L (0.76-1.84 MUg/L) and 1.09 MUg/L (0.72-1.31 MUg/L)
      in women with preeclampsia and normotensive, respectively; values for placental
      cadmium levels of women with preeclampsia and normotensive were 3.61 MUg/kg (2.19
      4.37 MUg/kg) and 4.28 MUg/kg (3.06-5.71 MUg/kg), respectively. We observed a
      statistically significant increase in blood and placental cadmium levels in women
      with preeclampsia compared to healthy pregnant women. After adjusting for pre
      pregnancy body mass index, maternal age, parity, gestational age at sample
      collection, and maternal calcium and magnesium levels, the odds ratio of having
      preeclampsia in the high tertile was markedly increased (odds ratio, 7.83 [95%
      CI, 1.64-37.26]) compared with the low tertile. Interestingly, there was no
      difference in the cadmium level in umbilical cord blood between the groups.
      Within the preeclamptic group, higher cadmium status was significantly associated
      with decreased birth weight. Our study suggested that elevated cadmium level in
      the maternal circulation could potentially increase the risk of preeclampsia. The
      results also demonstrate that higher cadmium status may contribute to fetal
      growth restriction in preeclamptic patients.

PMID- 29651731
TI  - Identification of Sialic Acid Linkages on Intact Glycopeptides via Differential
      Chemical Modification Using IntactGIG-HILIC.
AB  - Mass spectrometric analysis of intact glycopeptides can reveal detailed
      information about glycosite, glycan structural features, and their heterogeneity.
      Sialyl glycopeptides can be positively, negatively, or neutrally charged
      depending on pH of their buffer solution and ionization conditions. To detect
      sialoglycopeptides, a negative-ion mode mass spectrometry may be applied with a
      minimal loss of sialic acids, although the positively charged or neutral
      glycopeptides may be excluded. Alternatively, the sialyl glycopeptides can be
      identified using positive-ion mode analysis by doping a high concentration of
      sodium salts to the analytes. Although manipulation of unmodified
      sialoglycopeptides can be useful for analysis of samples, less than optimal
      ionization, facile loss of sialyl and unfavorable ionization of accompanying non
      sialyl peptides make such strategies suboptimal. Currently available chemical
      derivatization methods, while stabilizing for sialic acid, mask sialic acid
      linkage configuration. Here, we report the development of a novel approach to
      neutralize sialic acids via sequentially chemical modification that also reveals
      their linkage configuration, often an important determinant in biological
      function. This method utilizes several components to facilitate glycopeptide
      identification. These include the following: solid phase derivatization, enhanced
      ionization of sialoglycopeptides, differentiation of sialic acid linkage, and
      enrichment of the modified glycopeptides by hydrophilic interaction liquid
      chromatography. This technology can be used as a tool for quantitative analysis
      of protein sialylation in diseases with determination of sialic acid linkage
      configuration. Graphical Abstract ?.

PMID- 29651733
TI  - Interaction of Zn with Losartan. Activation of Intrinsic Apoptotic Signaling
      Pathway in Lung Cancer Cells and Effects on Alkaline and Acid Phosphatases.
AB  - A new losartan [2-butyl-5-chloro-3-[[4-[2-(2H-tetrazol-5
      yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol zinc(II) complex [Zn(Los)Cl], was
      synthesized and characterized. The crystal structure was determined by x-ray
      diffraction methods. When aqueous solutions of the ligand and the metal were
      mixed, the known and more soluble powder [Zn(Los)2].3H2O (ZnLos) complex has been
      obtained. The interactions with phosphatases showed a concerted mechanism
      displayed by the Zn ions and ZnLos up to 500 MUM concentration: a decrease of the
      acid phosphatase (AcP) associated with an increase in the alkaline phosphatase
      (ALP) activities. The complex and ZnSO4 showed a cytotoxic behavior on human lung
      A549 cancer cell line at concentrations higher than 75 MUM with reactive oxygen
      species (ROS) generation and GSH (and GSH/GSSG ratio) depletion. Apoptotic cells
      were observed using terminal deoxynucleotidyl transferase dUTP nick-end labeling
      (TUNEL) method, a mechanism accompanied by upregulation of BAX protein,
      downregulation of Bcl-XL and release of caspase-3. The BAX/Bcl-XL ratio was found
      to be significantly higher in cells exposure to ZnLos than cells treated with
      ZnSO4, in agreement with the higher apoptotic percentage of cells found for the
      complex. Cell death was found to be produced by apoptosis and no necrosis has
      been observed. On the contrary, losartan exerted low effects on phosphatases,
      produced some reduction of cancer cell viability (concentrations > 250 MUM,
      number of apoptotic cells similar to the basal) with low ROS depletion, without
      alteration of the GSH/GSSG and low BAX/Bcl-XL ratios. In the MRC-5, normal lung
      fibroblasts cell line only ZnSO4 at concentrations higher than 200 MUM displays
      cytotoxic effects. Graphical abstract Interaction of Zn with losartan. Activation
      of intrinsic apoptotic signaling pathway in lung cancer cells and effects on
      alkaline and acid phosphatases.

PMID- 29651734
TI  - Palivizumab use in infants with Down syndrome-report from the German SynagisTM
      Registry 2009-2016.
AB  - : Infants with Down syndrome (DS) face an increased risk of respiratory tract
      infections. Recent studies describe DS as independent risk factor for a
      complicated clinical course in infants with respiratory syncytial virus (RSV)
      infection. The prospective observational German SynagisTM Registry comprises data
      from 249 children below 25 months of age with DS and palivizumab prophylaxis 2009
      2016 (1191 administrations; mean 4.8 per patient and season). The median
      gestational age and the birth weight in patients without and with DS were 31
      versus 37 weeks (P < 0.001) and 1590 versus 2750 g, respectively (P < 0.001).
      Patients with DS significantly more often had congenital heart disease (CHD),
      siblings in kindergarten or school, treatment with oxygen at home,
      immunodeficiency, and neuromuscular impairment. The RSV-related hospitalization
      rate in patients with DS was 1.20%; the hospitalization rate in patients without
      DS was 0.71%. CONCLUSION: Data from 249 children with DS receiving palivizumab
      prophylaxis in seven consecutive RSV seasons (2009-2016) in Germany reveal
      important differences between patients with and without DS concerning the main
      indication for palivizumab use and additional risk factors. Bearing in mind the
      limitations of an uncontrolled postmarketing observational study, the results
      confirm the field effectiveness of palivizumab prophylaxis in this special
      population. What is Known: * Recent studies describe the Down syndrome as
      independent risk factor for a complicated clinical course in infants with RSV
      infection. What is New: * Compared with other infants receiving palivizumab
      prophylaxis, patients with Down syndrome significantly more often had congenital
      heart disease, siblings in kindergarten or school, treatment with oxygen at home,
      immunodeficiency, and neuromuscular impairment. * In infants with palivizumab
      prophylaxis breakthrough, RSV-related hospitalization rates were not
      significantly higher in those with Down syndrome.

PMID- 29651735
TI  - Coroners and PTSD: Treatment Implications.
AB  - Experimental studies have documented the development of posttraumatic stress
      disorder (PTSD) in first responders. These studies have routinely included
      police, firefighters, and paramedics. However, there is another group of first
      responders that are at risk for PTSD but that has received less research
      attention. This group is comprised of coroners. This paper reviewed the published
      data concerning coroners and PTSD and outlined various treatments for addressing
      coronial PTSD. The findings, the differing treatments, and a detailed
      methodological inquiry are presented. The need for a conceptual framework for the
      various other professional groups responding to critical incidents and a crisis
      intervention approach to address the psychological needs of both family survivors
      and coronial personnel are noted.

PMID- 29651736
TI  - Nuclear cardiology in the literature: A selection of recent, original research
      papers.

PMID- 29651737
TI  - Balancing statistical significance and clinical relevance.

PMID- 29651738
TI  - Chronic total occlusion without collateral blood flow does not exclude myocardial
      viability and subsequent recovery after revascularization.

PMID- 29651739
TI  - Prognostic utility of splenic response ratio in dipyridamole PET myocardial
      perfusion imaging.
AB  - BACKGROUND: Cardiac magnetic resonance perfusion studies with adenosine stress
      have shown that splenic response can identify patients with inadequate
      pharmacologic stress. We investigate the incremental prognostic impact of splenic
      response ratio (SRR) in patients with normal Rubidium (Rb)-82 PET myocardial
      perfusion imaging (MPI). METHODS: Consecutive patients undergoing dipyridamole Rb
      82 PET MPI for the evaluation of coronary artery disease were screened. Spleen
      and liver Rb-82 activity was measured and the SRR was calculated: SRR = (Spleen
      stress/Liver stress)/(Spleen rest/Liver rest). Major adverse cardiac events
      (MACE) were determined at 1 year of follow-up in patients with normal summed
      stress score and normal summed difference score. RESULTS: Of the 839 patients
      screened, the spleen was visualized in 703 (84%) of scans. There was
      significantly higher MACE observed in splenic non-responders vs splenic
      responders in both the normal SSS (7.8% vs 2.9%, P = .027) and the normal SDS
      groups (7.4% vs 2.2%, P = .014). In multivariate analysis in patients with normal
      SDS, splenic response was a significant, independent predictor of MACE (HR 2.97,
      95% CI 1.10 to 8.04, P = .033). CONCLUSIONS: SRR is a novel imaging metric to
      identify patients with sub-maximal vasodilator stress and an incremental
      prognostic marker in patients with normal SDS and SSS (Clinical Trial
      Registration: https://clinicaltrials.gov/ct2/show/NCT01128023 ).

PMID- 29651741
TI  - Flash glucose monitoring: objective, not self-referential, outcomes are needed.

PMID- 29651740
TI  - The Expanding Role of Ketamine in the Emergency Department.
AB  - Patients frequently come to the emergency department for pain. For decades,
      ketamine has been used in the emergency department for procedural sedation but is
      now receiving attention as a potential alternative to opioids because of its
      unique analgesic effects. Additionally, ketamine's dissociative properties have
      made it a popular choice for sedating profoundly agitated patients. In this
      narrative review, these new roles for ketamine in the emergency department are
      discussed.

PMID- 29651742
TI  - A scientific approach to the reform of a medical curriculum : A personal account
      of the Vienna experience.
AB  - Planning and implementing a new curriculum at the Medical Faculty of the
      University of Vienna was a bold attempt to use a scientific approach. A
      curriculum of sequentially presented and departmentally controlled subject areas
      using oral examinations was replaced with horizontally and vertically integrated
      organ/function modules. The reform also introduced integrated written year-end
      examinations, a required research thesis, stronger clinical orientation starting
      already in the 1st semester and more elective components. The starting point,
      preparatory work, the legal framework, as well as the formal planning process
      from January 1998 until October 2001 are described and explained.

PMID- 29651743
TI  - Polypharmacy in palliative care-COPD and multimorbidity : A case report.
AB  - This is the case report of an 80-year-old woman with advanced chronic obstructive
      pulmonary disease (COPD), multimorbidity and frailty. Despite regular critical re
      evaluation of on-going medication, a significant reduction of prescribed
      medication was not achieved up until the patient's terminal phase, and this may
      have contributed to several episodes of delirium. It was particularly difficult
      to reduce the number of prescribed drugs due to cardiovascular, endocrinologic,
      orthopaedic, neurologic, psychiatric and pulmonary comorbidities. Probable drug
      drug interactions and side effects were repeatedly observed. This case report
      aims to describe a dilemma frequently encountered in the care of patients with
      progressed pulmonary disease in the context of frailty and multimorbidity.

PMID- 29651744
TI  - Prospects of chimeric antigen receptor T cell therapy in ovarian cancer.
AB  - Despite advances in various chemotherapy regimens, current therapeutic options
      are limited for ovarian cancer patients. Immunotherapy provides a promising and
      novel treatment option for ovarian cancer. Recently, chimeric antigen receptor
      (CAR) T cell therapy has shown promising results in hematological tumors and
      current research is going on in various solid tumors like ovarian cancer. CAR T
      cells are genetically engineered T cells with major histocompatibility complex
      independent, tumor-specific, immune-mediated cytolytic actions against cancer
      cells. Initial studies of CAR T cell therapy have shown promising results in
      ovarian cancer, but there are some obstacles like impaired T cell trafficking,
      lack of antigenic targets, cytokine release syndrome and most important
      immunosuppressive tumor microenvironment. Optimization of design, improving tumor
      microenvironment and combinations with other therapies may help us in improving
      CAR T cell efficacy. In this review article, we highlight the current knowledge
      regarding CAR T cell therapy in ovarian cancer. We have discussed basic
      functioning of CAR T cells, their rationale and clinical outcome in ovarian
      cancer with limitations.

PMID- 29651745
TI  - Correlations between age, functional status, and the senescence-associated
      proteins HMGB2 and p16INK4a.
AB  - Cellular senescence is a central component of the aging process. This cellular
      response has been found to be induced by multiple forms of molecular damage and
      senescent cells increase in number with age in all tissues examined to date. We
      have examined the correlation with age of two key proteins involved in the
      senescence program, p16INK4a and HMGB2. These proteins are involved in cell cycle
      arrest and chromatin remodeling during senescence. Circulating levels of these
      markers increases with age and correlates with functional status. The levels of
      HMGB2 appear to be significantly correlated with functional status, whereas
      p16INK4a levels are more weakly associated. Interestingly, there is a strong
      correlation between the two proteins independent of age. In particular, a single
      high-functioning individual over 90 years of age displays a disproportionately
      low level of HGMB2. The results suggest that with improved testing methodology,
      it may be possible to monitor circulating protein markers of senescence in human
      populations.

PMID- 29651746
TI  - Human Neural Stem/Progenitor Cells Derived From Epileptic Human Brain in a Self
      Assembling Peptide Nanoscaffold Improve Traumatic Brain Injury in Rats.
AB  - Traumatic brain injury (TBI) is a disruption in the brain functions following a
      head trauma. Cell therapy may provide a promising treatment for TBI. Among
      different cell types, human neural stem cells cultured in self-assembling peptide
      scaffolds have been suggested as a potential novel method for cell replacement
      treatment after TBI. In the present study, we accessed the effects of human
      neural stem/progenitor cells (hNS/PCs) derived from epileptic human brain and
      human adipose-derived stromal/stem cells (hADSCs) seeded in PuraMatrix hydrogel
      (PM) on brain function after TBI in an animal model of brain injury. hNS/PCs were
      isolated from patients with medically intractable epilepsy undergone epilepsy
      surgery. hNS/PCs and hADSCs have the potential for proliferation and
      differentiation into both neuronal and glial lineages. Assessment of the growth
      characteristics of hNS/PCs and hADSCs revealed that the hNS/PCs doubling time was
      significantly longer and the growth rate was lower than hADSCs. Transplantation
      of hNS/PCs and hADSCs seeded in PM improved functional recovery, decreased lesion
      volume, inhibited neuroinflammation, and reduced the reactive gliosis at the
      injury site. The data suggest the transplantation of hNS/PCs or hADSCs cultured
      in PM as a promising treatment option for cell replacement therapy in TBI.

PMID- 29651748
TI  - Improved Reperfusion and Vasculoprotection by the Poly(ADP-Ribose)Polymerase
      Inhibitor PJ34 After Stroke and Thrombolysis in Mice.
AB  - Benefits from thrombolysis with recombinant tissue plasminogen activator (rt-PA)
      after ischemic stroke remain limited due to a narrow therapeutic window, low
      reperfusion rates, and increased risk of hemorrhagic transformations (HT).
      Experimental data showed that rt-PA enhances the post-ischemic activation of
      poly(ADP-ribose)polymerase (PARP) which in turn contributes to blood-brain
      barrier injury. The aim of the present study was to evaluate whether PJ34, a
      potent PARP inhibitor, improves poor reperfusion induced by delayed rt-PA
      administration, exerts vasculoprotective effects, and finally increases the
      therapeutic window of rt-PA. Stroke was induced by thrombin injection (0.75 UI in
      1 MUl) in the left middle cerebral artery (MCA) of male Swiss mice.
      Administration of rt-PA (0.9 mg kg-1) or saline was delayed for 4 h after
      ischemia onset. Saline or PJ34 (3 mg kg-1) was given intraperitoneally twice,
      just after thrombin injection and 3 h later, or once, 3 h after ischemia onset.
      Reperfusion was evaluated by laser Doppler, vascular inflammation by
      immunohistochemistry of vascular cell adhesion molecule-1 (VCAM-1) expression,
      and vasospasm by morphometric measurement of the MCA. Edema, cortical lesion, and
      sensorimotor deficit were evaluated. Treatment with PJ34 improved rt-PA-induced
      reperfusion and promoted vascular protection including reduction in vascular
      inflammation (decrease in VCAM-1 expression), HT, and MCA vasospasm.
      Additionally, the combined treatment significantly reduced brain edema, cortical
      lesion, and sensorimotor deficit. In conclusion, the combination of the PARP
      inhibitor PJ34 with rt-PA after cerebral ischemia may be of particular interest
      in order to improve thrombolysis with an extended therapeutic window.

PMID- 29651747
TI  - Tauroursodeoxycholic Acid Improves Motor Symptoms in a Mouse Model of Parkinson's
      Disease.
AB  - Parkinson's disease (PD) is characterized by severe motor symptoms, and currently
      there is no treatment that retards disease progression or reverses damage prior
      to the time of clinical diagnosis. Tauroursodeoxycholic acid (TUDCA) is
      neuroprotective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse
      model of PD; however, its effect in PD motor symptoms has never been addressed.
      In the present work, an extensive behavior analysis was performed to better
      characterize the MPTP model of PD and to evaluate the effects of TUDCA in the
      prevention/improvement of mice phenotype. MPTP induced significant alterations in
      general motor performance paradigms, including increased latency in the motor
      swimming, adhesive removal and pole tests, as well as altered gait, foot
      dragging, and tremors. TUDCA administration, either before or after MPTP,
      significantly reduced the swimming latency, improved gait quality, and decreased
      foot dragging. Importantly, TUDCA was also effective in the prevention of typical
      parkinsonian symptoms such as spontaneous activity, ability to initiate movement
      and tremors. Accordingly, TUDCA prevented MPTP-induced decrease of dopaminergic
      fibers and ATP levels, mitochondrial dysfunction and neuroinflammation. Overall,
      MPTP-injected mice presented motor symptoms that are aggravated throughout time,
      resembling human parkinsonism, whereas PD motor symptoms were absent or mild in
      TUDCA-treated animals, and no aggravation was observed in any parameter. The
      thorough demonstration of improvement of PD symptoms together with the
      demonstration of the pathways triggered by TUDCA supports a subsequent clinical
      trial in humans and future validation of the application of this bile acid in PD.

PMID- 29651750
TI  - Endoscopic transorbital surgery for spheno-orbital lesions: how I do it.
AB  - BACKGROUND: The endoscopic transorbital approach has been recently proposed for
      the surgical management of spheno-orbital lesions as an alternative to craniotomy
      surgeries. METHOD: We analyze the technical nuances and what we have changed as
      our experience increased after the first operations performed for 12 different
      spheno-orbital lesions. CONCLUSION: The endoscopic transorbital approach is
      useful for the treatment of selected spheno-orbital lesions and could represent
      an interesting option in experienced hands. More studies are needed to fully
      understand its potentialities and limitations.

PMID- 29651749
TI  - Medium-chain triglycerides supplement therapy with a low-carbohydrate formula can
      supply energy and enhance ammonia detoxification in the hepatocytes of patients
      with adult-onset type II citrullinemia.
AB  - Citrin, encoded by SLC25A13, constitutes the malate-aspartate shuttle, the main
      NADH-shuttle in the liver. Citrin deficiency causes neonatal intrahepatic
      cholestasis (NICCD) and adult-onset type II citrullinemia (CTLN2). Citrin
      deficiency is predicted to impair hepatic glycolysis and de novo lipogenesis,
      resulting in hepatic energy deficit. Secondary decrease in hepatic
      argininosuccinate synthetase (ASS1) expression has been considered a cause of
      hyperammonemia in CTLN2. We previously reported that medium-chain triglyceride
      (MCT) supplement therapy with a low-carbohydrate formula was effective in CTLN2
      to prevent a relapse of hyperammonemic encephalopathy. We present the therapy for
      six CTLN2 patients. All the patients' general condition steadily improved and
      five patients with hyperammonemic encephalopathy recovered from unconsciousness
      in a few days. Before the treatment, plasma glutamine levels did not increase
      over the normal range and rather decreased to lower than the normal range in some
      patients. The treatment promptly decreased the blood ammonia level, which was
      accompanied by a decrease in plasma citrulline levels and an increase in plasma
      glutamine levels. These findings indicated that hyperammonemia was not only
      caused by the impairment of ureagenesis at ASS1 step, but was also associated
      with an impairment of glutamine synthetase (GS) ammonia-detoxification system in
      the hepatocytes. There was no decrease in the GS expressing hepatocytes. MCT
      supplement with a low-carbohydrate formula can supply the energy and/or
      substrates for ASS1 and GS, and enhance ammonia detoxification in hepatocytes.
      Histological improvement in the hepatic steatosis and ASS1-expression was also
      observed in a patient after long-term treatment.

PMID- 29651751
TI  - Usefulness of venous catheter as an intraluminal stent for end-to-end venous
      anastomosis.
AB  - BACKGROUND: Venous anastomosis is one of the most difficult techniques in
      vascular neurosurgery. METHOD: We present a simple technique of end-to-end venous
      anastomosis for reconstruction of accidentally injured vein. A venous catheter
      was used for the stent during the end-to-end anastomosis. RESULTS: The venous
      catheter as the stent facilitated confirmation of the ostium of the vein. The
      venous end-to-end anastomosis was successfully performed. CONCLUSIONS: Accidental
      venous injury can be reconstructed with the present simple technique.

PMID- 29651752
TI  - On the limits of statistical learning: Intertrial contextual cueing is confined
      to temporally close contingencies.
AB  - Since the seminal study by Chun and Jiang (Cognitive Psychology, 36, 28-71,
      1998), a large body of research based on the contextual-cueing paradigm has shown
      that the cognitive system is capable of extracting statistical contingencies from
      visual environments. Most of these studies have focused on how individuals learn
      regularities found within an intratrial temporal window: A context predicts the
      target position within a given trial. However, Ono, Jiang, and Kawahara (Journal
      of Experimental Psychology, 31, 703-712, 2005) provided evidence of an intertrial
      implicit-learning effect when a distractor configuration in preceding trials N -
      1 predicted the target location in trials N. The aim of the present study was to
      gain further insight into this effect by examining whether it occurs when
      predictive relationships are impeded by interfering task-relevant noise
      (Experiments 2 and 3) or by a long delay (Experiments 1, 4, and 5). Our results
      replicated the intertrial contextual-cueing effect, which occurred in the
      condition of temporally close contingencies. However, there was no evidence of
      integration across long-range spatiotemporal contingencies, suggesting a temporal
      limitation of statistical learning.

PMID- 29651753
TI  - Numerical distance effect size is a poor metric of approximate number system
      acuity.
AB  - Individual differences in the ability to compare and evaluate nonsymbolic
      numerical magnitudes-approximate number system (ANS) acuity-are emerging as an
      important predictor in many research areas. Unfortunately, recent empirical
      studies have called into question whether a historically common ANS-acuity metric
      the size of the numerical distance effect (NDE size)-is an effective measure of
      ANS acuity. NDE size has been shown to frequently yield divergent results from
      other ANS-acuity metrics. Given these concerns and the measure's past popularity,
      it behooves us to question whether the use of NDE size as an ANS-acuity metric is
      theoretically supported. This study seeks to address this gap in the literature
      by using modeling to test the basic assumption underpinning use of NDE size as an
      ANS-acuity metric: that larger NDE size indicates poorer ANS acuity. This
      assumption did not hold up under test. Results demonstrate that the theoretically
      ideal relationship between NDE size and ANS acuity is not linear, but rather
      resembles an inverted J-shaped distribution, with the inflection points varying
      based on precise NDE task methodology. Thus, depending on specific methodology
      and the distribution of ANS acuity in the tested population, positive, negative,
      or null correlations between NDE size and ANS acuity could be predicted.
      Moreover, peak NDE sizes would be found for near-average ANS acuities on common
      NDE tasks. This indicates that NDE size has limited and inconsistent utility as
      an ANS-acuity metric. Past results should be interpreted on a case-by-case basis,
      considering both specifics of the NDE task and expected ANS acuity of the sampled
      population.

PMID- 29651754
TI  - Learning efficient visual search for stimuli containing diagnostic spatial
      configurations and color-shape conjunctions.
AB  - Visual search is often slow and difficult for complex stimuli such as feature
      conjunctions. Search efficiency, however, can improve with training. Search for
      stimuli that can be identified by the spatial configuration of two elements
      (e.g., the relative position of two colored shapes) improves dramatically within
      a few hundred trials of practice. Several recent imaging studies have identified
      neural correlates of this learning, but it remains unclear what stimulus
      properties participants learn to use to search efficiently. Influential models,
      such as reverse hierarchy theory, propose two major possibilities: learning to
      use information contained in low-level image statistics (e.g., single features at
      particular retinotopic locations) or in high-level characteristics (e.g., feature
      conjunctions) of the task-relevant stimuli. In a series of experiments, we tested
      these two hypotheses, which make different predictions about the effect of
      various stimulus manipulations after training. We find relatively small effects
      of manipulating low-level properties of the stimuli (e.g., changing their
      retinotopic location) and some conjunctive properties (e.g., color-position),
      whereas the effects of manipulating other conjunctive properties (e.g., color
      shape) are larger. Overall, the findings suggest conjunction learning involving
      such stimuli might be an emergent phenomenon that reflects multiple different
      learning processes, each of which capitalizes on different types of information
      contained in the stimuli. We also show that both targets and distractors are
      learned, and that reversing learned target and distractor identities impairs
      performance. This suggests that participants do not merely learn to discriminate
      target and distractor stimuli, they also learn stimulus identity mappings that
      contribute to performance improvements.

PMID- 29651755
TI  - Sensitivity to stimulus similarity is associated with greater sustained attention
      ability.
AB  - Sustained attention is critical for tasks where perceptual information must be
      continuously processed, like reading or driving; however, the cognitive processes
      underlying sustained attention remain incompletely characterized. In the
      experiments that follow, we explore the relationship between sustaining attention
      and the contents and maintenance of task-relevant features in an attentional
      template. Specifically, we administered the gradual onset continuous performance
      task (gradCPT), a sensitive measure of sustained attention, to a large web-based
      sample (N>20,000) and a smaller laboratory sample for validation and extension.
      The gradCPT requires participants to respond to most stimuli (city scenes - 90 %)
      and withhold to rare target images (mountain scenes - 10 %). By using stimulus
      similarity to probe the representational content of task-relevant features
      assuming either exemplar- or category-based feature matching-we predicted that
      RTs for city stimuli that were more "mountain-like" would be slower and "city
      like" mountain stimuli would elicit more erroneous presses. We found that
      exemplar-based target-nontarget (T-N) similarity predicted both RTs and erroneous
      button presses, suggesting a stimulus-specific feature matching process was
      adopted. Importantly, individual differences in the degree of sensitivity to
      these similarity measures correlated with conventional measures of attentional
      ability on the gradCPT as well as another CPT that is perceptually less
      demanding. In other words, individuals with greater sustained attention ability
      (assessed by two tasks) were more likely to be influenced by stimulus similarity
      on the gradCPT. These results suggest that sustained attention facilitates the
      construction and maintenance of an attentional template that is optimal for a
      given task.

PMID- 29651756
TI  - Aquatic Training in Upright Position as an Alternative to Improve Blood Pressure
      in Adults and Elderly: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Meta-analyses have shown that land training (LT) reduces blood
      pressure; however, it is not known whether aquatic training (AT) promotes this
      same effect. OBJECTIVE: The aim was to conduct a meta-analysis on the effects of
      AT on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in adults
      and elderly and compare them to those of LT and no training [control group (CG)].
      DATA SOURCES: Embase, PubMed, Cochrane and Scopus were searched up to May 2017.
      STUDY ELIGIBILITY CRITERIA: Studies that evaluated the effect of upright AT
      (i.e., AT performed in upright position) on the blood pressure of adult
      individuals and the elderly who did not present with cardiovascular disease
      (other than hypertension) were included. DATA ANALYSIS: Two independent reviewers
      screened search results, performed data extraction and assessed risk of bias.
      Random effect was used, and the effect size (ES) was calculated by using the
      standardized mean difference with a 95% confidence interval. RESULTS: AT promoted
      a reduction in SBP (ES - 1.47; 95% CI - 2.23 to - 0.70; p < 0.01) compared to CG.
      This effect is maintained with training progression (ES - 1.52; 95% CI - 2.70 to 
      0.33; p = 0.01) and no progression (ES - 1.43; 95% CI - 2.64 to - 0.23; p =
      0.02). These effects were significant only in hypertensive (ES - 2.20; 95% CI -
      2.72 to - 1.68; p < 0.01), and not in pre-hypertensive individuals. AT promoted a
      decrease in DBP (- 0.92; 95% CI - 1.27 to - 0.57; p < 0.01) after training with
      progression (- 0.81; 95% CI - 1.62 to - 0.001; p = 0.04) and no progression (-
      1.01; 95% CI - 1.40 to - 0.62; p < 0.01) in pre-hypertensive (- 1.12; 95% CI -
      1.53 to - 0.70; p < 0.01) and hypertensive patients (- 0.69; 95% CI - 1.31 to -
      0.06; p = 0.03). AT promoted similar reductions in SBP compared to LT; however,
      reduction of DBP in hypertensive patients was lower (1.82; 95% CI 0.84 to 2.79; p
      < 0.01). CONCLUSION: AT promotes blood pressure reduction in adults and elderly.
      The reduction in SBP in those performing AT is similar to those performing LT,
      but reduction of DBP is lower in the AT group compared to that in the LT group.
      SYSTEMATIC REVIEW REGISTRATION NUMBER: CRD42016049716.

PMID- 29651757
TI  - Comparison of 125I- and 111In-labeled peptide probes for in vivo detection of
      oxidized low-density lipoprotein in atherosclerotic plaques.
AB  - OBJECTIVE: Oxidized low-density lipoprotein (OxLDL) plays a pivotal role in
      atherosclerotic plaque destabilization, which suggests its potential as a nuclear
      medical imaging target. We previously developed radioiodinated 125I-AHP7, a
      peptide probe carrying a 7-residue sequence from the OxLDL-binding protein Asp
      hemolysin, for specific OxLDL imaging. Although 125I-AHP7 recognized OxLDL, it
      had low stability. Thus, to improve stability, we designed radiolabeled 22
      residue peptide probes, 125I-AHP22 and 111In-AHP22, which include the entire AHP7
      sequence, and evaluated the stability, activity, and applications of these probes
      in vitro and in vivo. METHODS: Probes consisting of a 21-residue peptide derived
      from the Asp-hemolysin sequence and an N-terminal Cys or aminohexanoic acid for
      labeling with 125I-N-(3-iodophenyl)maleimide or 111In diethylene triamine
      pentaacetic acid were termed 125I-AHP22 and 111In-AHP22. An in vitro-binding
      inhibition assay with OxLDL was performed using 125I-AHP7 as a radiotracer.
      Radioactivity accumulation in the atherosclerotic aorta and plasma intact
      fraction was evaluated 30 min after intravenous administration of probes in
      myocardial infarction-prone Watanabe heritable hyperlipidemic (WHHLMI) rabbits.
      RESULTS: 125I-AHP22 and 111In-AHP22 were synthesized in ~ 360 and 60 min,
      respectively, with > 98% radiochemical purities after RP-HPLC purification. An in
      vitro-binding assay revealed similar or greater inhibition of OxLDL binding by
      both In-AHP22 and I-AHP22 compared to I-AHP7. The fraction of intact 125I-AHP22
      and 111In-AHP22 in plasma was estimated to be approximately tenfold higher than
      that of 125I-AHP7. Both probes were rapidly cleared from the blood. 111In-AHP22
      had a 2.3-fold higher accumulation in WHHLMI rabbit aortas compared to control
      rabbits, which was similar to 125I-AHP7. However, 125I-AHP22 accumulated to
      similar levels in aortas of WHHLMI and control rabbits due to high nonspecific
      accumulation in normal aortas that could be due to high lipophilicity.
      CONCLUSIONS: 111In-AHP22, easily prepared within 1 h, showed moderate affinity
      for OxLDL, high stability in vivo, and high accumulation in atherosclerotic
      aortas. 111In-AHP22 could be a potential lead compound to develop future
      effective OxLDL imaging probes.

PMID- 29651759
TI  - Investigating the Support Networks for Mothers of a High-density Public Housing
      Community and the Effects of Housing Closures on These Support Systems.
AB  - Over the past few decades, public housing initiatives have focused on the
      decentralization of poverty by replacing high-density public housing (HDPH)
      models with lower-density, mixed-income models. This action has resulted in the
      displacement of families who had lived in these developments for generations. In
      past studies, public housing residents have been shown to have stronger social
      ties than those living in other types of assisted housing. Research on the
      dismemberment of US public housing has demonstrated a "root shock" or disruption
      in the support infrastructure in these resource-limited communities. The purpose
      of this study was to use intergenerational analysis to analyze support systems of
      mothers in a low-income community and to investigate how the dismemberment of a
      Chicago HDPH community, Cabrini Green, affected parenting experiences and support
      infrastructure. Two generations of the former HDPH community were interviewed:
      (Gen1) mothers who raised their children in Cabrini Green and (Gen2) their
      daughter(s) who were raised in Cabrini Green but who now raise their children
      elsewhere. Interviews were analyzed for common themes in relation to mental
      health, social support networks, and parenting experiences. Four main components
      of parenting support were identified: familial support, father of child support,
      community support, and institutional support. Interviews suggest that the closing
      of Cabrini-Green high-rise buildings impacted relative contributions from
      specific components of mothers' support infrastructure, particularly community
      and institutional support. Mothers with support void in one component of support
      had better outcomes if they had the reserve to compensate by increasing one or
      more other areas of support. Programs that foster other sources of parenting
      support during and after public housing closures may help to improve outcomes for
      mothers and their families. By analyzing the experiences of mothers of both
      generations, we also gain insight into how experiences of motherhood and support
      systems compared before and after Cabrini Green's dissolution as well as insight
      into the participants' views on the impact of the housing closing on the
      parenting experience.

PMID- 29651758
TI  - The role of emergency medicine clerkship e-Portfolio to monitor the learning
      experience of students in different settings: a prospective cohort study.
AB  - BACKGROUND: Although emergency departments provide acute care learning
      opportunities for medical students, student exposure to recommended curriculum
      presentations and procedures are limited. In this perspective, clinical
      environments providing learning opportunities for students should be monitored as
      part of an ongoing quality improvement process. This study aims to analyze
      student exposures and their involvement levels in two different hospitals (Tawam
      and Al Ain) so as to improve the teaching and learning activities. METHODS: This
      is a prospective study on all 76 final year medical students' electronic logbooks
      (e-Portfolio) of the academic year 2016/2017. RESULTS: Students recorded 5087
      chief complaints and 3721 procedures. The average patient and procedure exposure
      in a shift per student in Al Ain Hospital compared with Tawam Hospital were 7.2
      vs 6.4 and 5.8 vs 4.3, respectively. The highest full involvement with
      presentations was seen in the pediatric unit (67.1%, P < 0.0001). Urgent care
      shifts demonstrated the highest area of "full involvement" with procedures for
      our students (73.2%, P < 0.0001). Students' highest involvement with
      presentations and procedures were found during the night shifts (P < 0.0001, 66.5
      and 75.1%, respectively). CONCLUSIONS: The electronic portfolio has proven to be
      a very useful tool in defining the learning activities of final year medical
      students during their emergency medicine clerkship and in comparing activities in
      two different clinical settings. Data collected and analyzed using this e
      Portfolio has the potential to help medical educators and curriculum designers
      improve emergency medicine teaching and learning activities.

PMID- 29651760
TI  - Stabilization of Cd-, Pb-, Cu- and Zn-contaminated calcareous agricultural soil
      using red mud: a field experiment.
AB  - Red mud (RM) was used to remediate heavy metal-contaminated soils. Experiments
      with two different dosages of RM added to soils were carried out in this study.
      It was found that soil pH increased 0.3 and 0.5 unit with the dosage of 3 and 5%
      (wt%), respectively. At the dosage of 5%, the highest stabilization efficiencies
      for Cd, Pb, Cu and Zn reached 67.95, 64.21, 43.73 and 63.73%, respectively. The
      addition of RM obviously transferred Cd from the exchangeable fraction to the
      residual fraction. Meanwhile, in comparison with the control (no RM added), it
      reduced 24.38, 49.20, 19.42 and 8.89% of Cd, Pb, Cu and Zn in wheat grains at the
      RM addition dosage of 5%, respectively. At the same time, the yield of wheat
      grains increased 17.81 and 24.66% at the RM addition dosage of 3 and 5%,
      respectively. Finally, the addition of RM did not change the soil bacterial
      community. These results indicate that RM has a great potential in stabilizing
      heavy metals in calcareous agricultural soils.

PMID- 29651761
TI  - Computer-Based Readability Testing of Information Booklets for German Cancer
      Patients.
AB  - Understandable health information is essential for treatment adherence and
      improved health outcomes. For readability testing, several instruments analyze
      the complexity of sentence structures, e.g., Flesch-Reading Ease (FRE) or Vienna
      Formula (WSTF). Moreover, the vocabulary is of high relevance for readers. The
      aim of this study is to investigate the agreement of sentence structure and
      vocabulary-based (SVM) instruments. A total of 52 freely available German patient
      information booklets on cancer were collected from the Internet. The mean
      understandability level L was computed for 51 booklets. The resulting values of
      FRE, WSTF, and SVM were assessed pairwise for agreement with Bland-Altman plots
      and two-sided, paired t tests. For the pairwise comparison, the mean L values are
      LFRE = 6.81, LWSTF = 7.39, LSVM = 5.09. The sentence structure-based metrics gave
      significantly different scores (P < 0.001) for all assessed booklets, confirmed
      by the Bland-Altman analysis. The study findings suggest that vocabulary-based
      instruments cannot be interchanged with FRE/WSTF. However, both analytical
      aspects should be considered and checked by authors to linguistically refine
      texts with respect to the individual target group. Authors of health information
      can be supported by automated readability analysis. Health professionals can
      benefit by direct booklet comparisons allowing for time-effective selection of
      suitable booklets for patients.

PMID- 29651762
TI  - Experience of neuroprotective air injection during radiofrequency ablation (RFA)
      of spinal osteoid osteoma.
AB  - PURPOSE: To assess the usefulness of epidural air injection during the RFA
      treatment of spinal osteoid osteoma. METHODS: A retrospective review of 17
      patients who underwent RFA for spinal osteoid osteoma between September 2006 and
      May 2017 was performed. All the procedures were performed by a single
      radiologist. We reviewed the perioperative CT studies to assess the distribution
      of air relative to the osteoid osteoma. The clinical outcome of each patient
      group was evaluated during routine follow-up. RESULTS: Seventeen patients were
      treated for spinal OO (male:female 13:4; mean age was 16, ranging from 4 to 42).
      The nidus size ranged from 5.8 to 17.2 mm (mean 11.2). In nine cases epidural air
      injection was performed. In three cases the neuroprotective air was deemed
      satisfactory with a clear layer of air between the osteoid osteoma and the dural
      sac being visualised. In six patients adherence between the cortical bone
      immediately adjacent to the osteoid osteoma and the dural sac in contact was
      observed. In 15 patients the procedure was successful in terms of pain relief. No
      neural damage or other complication was reported in either group. CONCLUSION: RFA
      is a safe treatment for spinal osteoid osteoma. Neuroprotective air injection
      does not appear to be necessary when performing the treatment in the spine. KEY
      POINTS: * Seventeen patients with spinal OO were treated with RFA, nine with air
      injection and eight without. Clinically successful treatment was achieved in 15
      patients, with 2 subsequently undergoing surgery * In 6/9 cases the injected air
      failed to achieve separation between the osteoid osteoma and the thecal sac
      because of inflammatory adhesion * No complications were observed, regardless of
      whether neuroprotective air was instilled. Neuroprotective air injection appears
      unnecessary when treating spinal OO.

PMID- 29651763
TI  - Computer-aided diagnosis prior to conventional interpretation of prostate mpMRI:
      an international multi-reader study.
AB  - OBJECTIVES: To evaluate if computer-aided diagnosis (CAD) prior to prostate multi
      parametric MRI (mpMRI) can improve sensitivity and agreement between
      radiologists. METHODS: Nine radiologists (three each high, intermediate, low
      experience) from eight institutions participated. A total of 163 patients with 3
      T mpMRI from 4/2012 to 6/2015 were included: 110 cancer patients with
      prostatectomy after mpMRI, 53 patients with no lesions on mpMRI and negative TRUS
      guided biopsy. Readers were blinded to all outcomes and detected lesions per PI
      RADSv2 on mpMRI. After 5 weeks, readers re-evaluated patients using CAD to detect
      lesions. Prostatectomy specimens registered to MRI were ground truth with index
      lesions defined on pathology. Sensitivity, specificity and agreement were
      calculated per patient, lesion level and zone-peripheral (PZ) and transition
      (TZ). RESULTS: Index lesion sensitivity was 78.2% for mpMRI alone and 86.3% for
      CAD-assisted mpMRI (p = 0.013). Sensitivity was comparable for TZ lesions (78.7%
      vs 78.1%; p = 0.929); CAD improved PZ lesion sensitivity (84% vs 94%; p = 0.003).
      Improved sensitivity came from lesions scored PI-RADS < 3 as index lesion
      sensitivity was comparable at PI-RADS >= 3 (77.6% vs 78.1%; p = 0.859). Per
      patient specificity was 57.1% for CAD and 70.4% for mpMRI (p = 0.003). CAD
      improved agreement between all readers (56.9% vs 71.8%; p < 0.001). CONCLUSIONS:
      CAD-assisted mpMRI improved sensitivity and agreement, but decreased specificity,
      between radiologists of varying experience. KEY POINTS: * Computer-aided
      diagnosis (CAD) assists clinicians in detecting prostate cancer on MRI. * CAD
      assistance improves agreement between radiologists in detecting prostate cancer
      lesions. * However, this CAD system induces more false positives, particularly
      for less-experienced clinicians and in the transition zone. * CAD assists
      radiologists in detecting cancer missed on MRI, suggesting a path for improved
      diagnostic confidence.

PMID- 29651764
TI  - Can functional parameters from hepatobiliary phase of gadoxetate MRI predict
      clinical outcomes in patients with cirrhosis?
AB  - OBJECTIVES: To determine the value of quantitative parameters of gadoxetate
      enhanced magnetic resonance imaging (MRI) in predicting prognosis in patients
      with cirrhosis. METHODS: A cohort of 63 cirrhotic patients who had gadoxetate MRI
      and 2-year clinical follow-up was enrolled. Enhancement ratio (ER), contrast
      enhancement index (CEI) and contrast enhancement spleen index (CES) were
      calculated. The usefulness of these parameters and clinical scores, such as Child
      Pugh score (CPS) and model for end stage liver disease (MELD), in predicting
      adverse outcomes, such as variceal bleeding (VB), hepatic encephalopathy (HE) and
      mortality at 2 years were evaluated. RESULTS: Fifteen, 31 and 27 patients,
      respectively, had VB, HE and mortality within 2 years. The ER at 15 min (ER 15)
      and CES at 20 min (CES 20) were found to be the best MRI predictors. Areas under
      the receiver operating characteristic curve (AUC) for predicting VB were 0.785,
      0.729, 0.673, 0.714, respectively, for ER 15, CES 20, CPS and MELD scores. ER 15
      of less than 48 had sensitivity of 96% and specificity of 84% for predicting
      onset of HE within 2 years. CONCLUSIONS: In patients with cirrhosis, ER 15 or CES
      20 were equivalent or better predictors of major morbidity and mortality compared
      with commonly used clinical scores. KEY POINTS: * Gadoxetate parameters may
      identify cirrhotic patients at risk of adverse events. * Gadoxetate parameters
      usually show superior predictive values compared to clinical scores. * CES 20
      score is associated with risk of mortality within 2 years.

PMID- 29651765
TI  - T2-weighted balanced steady-state free procession MRI evaluated for diagnosing
      placental adhesion disorder in late pregnancy.
AB  - OBJECTIVE: This study evaluated the imaging characteristics and accuracy of T2
      weighted (T2W) balanced steady-state free procession (b-SSFP) magnetic resonance
      imaging, relative to b-SSFP or single-shot fast spin echo (SSFSE), for the
      diagnosis of placental adhesion disorder (PAD). METHODS: Fifty-one pregnant
      patients suspected of PAD were examined with T2W b-SSFP, b-SSFP and SSFSE. The
      image types were independently analysed for signs of PAD: abnormal placental
      bulge (APB), dark intraplacental bands (DIB), placental heterogeneity (PH) and
      placental protrusion into adjacent structures (PPAS). The sequences were compared
      for muscle-to-placenta signal ratio, signs of PAD and area under the receiver
      operating characteristic curve (AUC) for diagnostic accuracy of PAD. RESULTS: PAD
      was confirmed in 34 women. The muscle-to-placenta signal ratio was highest in the
      T2W b-SSFP. The diagnostic rates of APB in T2W b-SSFP were comparable to that of
      b-SSFP, but were significantly higher than that of SSFSE. The rates of PH in SSFE
      were comparable to that of b-SSFP, but both were significantly lower than that of
      T2W b-SSFP. The rates of DIB were significantly higher in T2W b-SSFP images
      compared with SSFSE. Rates of PPAS were comparable among three sequences. The
      AUCs of the T2W b-SSFP, b-SSFP and SSFSE were 0.966, 0.890 and 0.823,
      respectively. CONCLUSION: T2W b-SSFP has high diagnostic accuracy for PAD
      relative to SSFSE or b-SSFP, which may be due to its high SNR, T2-weighting and
      lack of blur. KEY POINTS: * Signal myometrium-to-placenta ratio was highest in
      the T2W b-SSFP images. * Diagnostic rate of APB in T2W b-SSFP was highest. *
      Diagnostic rate of DIB was higher in T2W b-SSFP than in SSFSE. * Diagnostic rate
      of PH in T2W b-SSFP was highest. * Maximum AUC for diagnostic accuracy of PAD was
      in T2W b-SSFP.

PMID- 29651766
TI  - Early osteosclerotic changes predict chemotherapy response in non-small-cell lung
      cancer patients with bone metastases.
AB  - OBJECTIVES: To explore the relationship between osteosclerotic changes and
      chemotherapy response in non-small-cell lung cancer (NSCLC) patients with bone
      metastases (BM). METHODS: Fifty-two NSCLC patients with BM were enrolled from 1
      January 2010-31 June 2015 and divided into two groups based on their CT features:
      an osteosclerotic change (OC) group and a no-osteosclerotic change (NOC) group.
      The disease control rate (DCR) was evaluated, and progression-free survival (PFS)
      was analysed using Kaplan-Meier curves. Univariate and multivariate Cox
      regression analyses were performed to analyse the factors that could affect PFS.
      RESULTS: Osteosclerotic changes were observed in 35/52 patients. The median
      interval when osteosclerotic changes occurred was 2 months (range 1-3 months)
      after chemotherapy. The OC group had a significantly higher 3-month DCR than the
      NOC group (p < 0.001). The OC group had a higher 1-year PFS rate than the NOC
      group (1-year PFS: 74.9% vs. 30.2%, p < 0.001). Univariate Cox regression
      analysis indicated that pathological subtype (HR = 4.419; 95% CI = 1.635-11.941,
      p = 0.003) and osteosclerotic changes (HR = 0.199; 95% CI = 0.083-0.477, p <
      0.001) were significant predictors of PFS. CONCLUSION: Early osteosclerotic
      changes predict chemotherapy response in NSCLC patients with BM. KEY POINTS: *
      Osteosclerotic changes were prevalent CT features after chemotherapy in NSCLC
      patients. * Osteosclerotic changes were positively related to increased 3-month
      DCR. * Osteosclerotic changes were positively related to increased 1-year PFS
      rate.

PMID- 29651767
TI  - Radiation burden and associated cancer risk for a typical population to be
      screened for lung cancer with low-dose CT: A phantom study.
AB  - OBJECTIVES: To estimate (a) organ doses and organ-specific radiation-induced
      cancer risk from a single low-dose CT (LDCT) for lung cancer screening (LCS) and
      (b) the theoretical cumulative risk of radiation-induced cancer for a typical
      cohort to be subjected to repeated annual LCS LDCT. METHODS: Sex- and body size
      specific organ dose data from scan projection radiography (SPR) and helical CT
      exposures involved in LCS 256-slice LDCT were determined using Monte Carlo
      methods. Theoretical life attributable risk (LAR) of radiogenic cancer from a
      single 256-slice chest LDCT at age 55-80 years and the cumulative LAR of cancer
      from repeated annual LDCT studies up to age 80 years were estimated and compared
      to corresponding nominal lifetime intrinsic risks (LIRs) of being diagnosed with
      cancer. RESULTS: The effective dose from LCS 256-slice LDCT was estimated to be
      0.71 mSv. SPR was found to contribute 6-12 % to the total effective dose from
      chest LDCT. The radiation-cancer LAR from a single LDCT study was found to
      increase the nominal LIR of cancer in average-size 55-year-old males and females
      by 0.008 % and 0.018 %, respectively. Cumulative radiogenic risk of cancer from
      repeated annual scans from the age of 55-80 years was found to increase the
      nominal LIR of cancer by 0.13 % in males and 0.30 % in females. CONCLUSION:
      Modern scanners may offer sub-millisievert LCS LDCT. Cumulative radiation risk
      from repeated annual 256-slice LDCT LCS examinations was found to minimally
      aggravate the lifetime intrinsic cancer risk of a typical screening population.
      KEY POINTS: * Effective dose from lung cancer screening low-dose CT may be <1
      mSv. * Screening with modern low-dose CT minimally aggravates lifetime cancer
      induction intrinsic risk. * Dosimetry of lung cancer screening low-dose CT should
      encounter the radiation burden from the localizing scan projection radiography. *
      DLP method may underestimate effective dose from low-dose chest CT by 27 %.

PMID- 29651768
TI  - Minimisation of Signal Intensity Differences in Distortion Correction Approaches
      of Brain Magnetic Resonance Diffusion Tensor Imaging.
AB  - OBJECTIVES: To evaluate the effects of signal intensity differences between the
      b0 image and diffusion tensor imaging (DTI) in the image registration process.
      METHODS: To correct signal intensity differences between the b0 image and DTI
      data, a simple image intensity compensation (SIMIC) method, which is a b0 image
      re-calculation process from DTI data, was applied before the image registration.
      The re-calculated b0 image (b0ext) from each diffusion direction was registered
      to the b0 image acquired through the MR scanning (b0nd) with two types of cost
      functions and their transformation matrices were acquired. These transformation
      matrices were then used to register the DTI data. For quantifications, the dice
      similarity coefficient (DSC) values, diffusion scalar matrix, and quantified
      fibre numbers and lengths were calculated. RESULTS: The combined SIMIC method
      with two cost functions showed the highest DSC value (0.802 +/- 0.007). Regarding
      diffusion scalar values and numbers and lengths of fibres from the corpus
      callosum, superior longitudinal fasciculus, and cortico-spinal tract, only using
      normalised cross correlation (NCC) showed a specific tendency toward lower values
      in the brain regions. CONCLUSION: Image-based distortion correction with SIMIC
      for DTI data would help in image analysis by accounting for signal intensity
      differences as one additional option for DTI analysis. KEY POINTS: * We evaluated
      the effects of signal intensity differences at DTI registration. * The non
      diffusion-weighted image re-calculation process from DTI data was applied. *
      SIMIC can minimise the signal intensity differences at DTI registration.

PMID- 29651769
TI  - Superolateral Hoffa's fat pad (SHFP) oedema and patellar cartilage volume loss:
      quantitative analysis using longitudinal data from the Foundation for the
      National Institute of Health (FNIH) Osteoarthritis Biomarkers Consortium.
AB  - OBJECTIVES: To determine the association of superolateral Hoffa's fat pad (SHFP)
      oedema and patellofemoral joint structural damage in participants of Foundation
      for the National Institute of Health Osteoarthritis Biomarkers Consortium study.
      METHODS: Baseline and 24-month MRIs of 600 subjects were assessed. The presence
      of SHFP oedema (using 0-3 grading scale) and patellar morphology metrics were
      determined using baseline MRI. Quantitative patellar cartilage volume and semi
      quantitative MRI osteoarthritis knee score (MOAKS) variables were extracted. The
      associations between SHFP oedema and patellar cartilage damage, bone marrow
      lesion (BML), osteophyte and morphology were evaluated in cross-sectional model.
      In longitudinal analysis, the associations between oedema and cartilage volume
      loss (defined using reliable change index) and MOAKS worsening were evaluated.
      RESULTS: In cross-sectional evaluations, the presence of SHFP oedema was
      associated with simultaneous lateral patellar cartilage/BML defects and inferior
      medial patellar osteophyte size. A significant positive correlation between the
      degree of patella alta and SHFP oedema was detected (r = 0.259, p < 0.001). The
      presence of oedema was associated with 24-month cartilage volume loss (odds ratio
      (OR) 2.11, 95% confidence interval 1.46-3.06) and medial patellar BML size (OR
      1.92 (1.15-3.21)) and number (OR 2.50 (1.29-4.88)) worsening. The optimal cut-off
      value for the grade of baseline SHFP oedema regarding both presence and worsening
      of patellar structural damage was >= 1 (presence of any SHFP hyperintensity).
      CONCLUSIONS: The presence of SHFP oedema could be considered as a predictor of
      future patellar cartilage loss and BML worsening, and an indicator of
      simultaneous cartilage, BML and osteophyte defects. KEY POINTS: * SHFP oedema was
      associated with simultaneous lateral patellar OA-related structural damage. *
      SHFP oedema was associated with longitudinal patellar cartilage loss over 24
      months. * SHFP oedema could be considered as indicator and predictor of patellar
      OA.

PMID- 29651770
TI  - The inhibitory effect of gadoxetate disodium on hepatic transporters: a study
      using indocyanine green.
AB  - OBJECTIVES: To assess the inhibitory effect of gadoxetate disodium on the
      transporter system using indocyanine green (ICG). MATERIALS AND METHODS: Groups
      of six female B6 Albino mice were injected with the test agent (0.62 mmol/kg
      gadoxetate disodium) or phosphate-buffered saline (control) 10 min before
      injection of ICG. Identical fluorescence images were subsequently obtained to
      create time-efficiency curves of liver parenchymal uptake. The study was
      performed on hypothermic and normothermic mice. The logarithms of the absorption
      rate constants (logKa values) and of the elimination rate constants (logKe
      values) were calculated for each experimental condition, and between-group
      differences were compared using Student's t-test. RESULTS: The logKe values of
      the test group were lower than those of the control group at both temperatures (
      6.52 vs. -5.87 under hypothermic conditions and -4.54 vs. -4.14 under
      normothermic conditions), and both differences were statistically significant (p
      = 0.037, 0.015 respectively). In terms of the logKa values, although the
      difference did not reach statistical significance (p = 0.052), the test group had
      lower values than the control group under hypothermic conditions (-0.771 vs. 
      0.376). In normothermic mice, the logKa values for the test and control groups
      were 0.037 and 0.277 respectively, thus not significantly different (p = 0.404).
      CONCLUSIONS: Gadoxetate disodium inhibited ICG excretion. Thus, gadoxetate
      disodium inhibited the ATP-binding cassette sub-family C member 2 transporter.
      KEY POINTS: * Gadoxetate disodium inhibited ICG excretion. * Gadoxetate disodium
      tended to inhibit hepatic ICG uptake. * Drug-drug interactions of gadoxetate
      disodium need further investigation.

PMID- 29651771
TI  - Remote brain microhaemorrhages may predict haematoma in glioma patients treated
      with radiation therapy.
AB  - OBJECTIVES: To evaluate the prevalence of cerebral remote microhaemorrhages (RMH)
      and remote haematomas (RH) using magnetic resonance susceptibility-weighted
      imaging (SWI) among patients treated for gliomas during follow-up. METHODS: We
      conducted a retrospective single centre longitudinal study on 58 consecutive
      patients treated for gliomas from January 2009 through December 2010. Our
      institutional review board approved this study. We evaluated the presence and
      number of RMH and RH found outside the brain tumour on follow-up MR imaging. We
      performed univariate and bivariate analyses to identify predictors for RMH and RH
      and Kaplan-Meier survival analysis techniques. RESULTS: Twenty-five (43%) and
      four patients (7%) developed at least one RMH or RH, respectively, during follow
      up. The risk was significantly higher for patients who received radiation therapy
      (49% and 8% versus 0%) (p = 0.02). The risk of developing RH was significantly
      higher in patients with at least one RMH and a high burden of RMH. The mean age
      of those presenting with at least one RMH or RH was significantly lower.
      CONCLUSIONS: RMH were common in adult survivors of gliomas who received radiation
      therapy and may predict the onset of RH during follow-up, mainly in younger
      patients. KEY POINTS: * Brain RMH and RH are significantly more likely to occur
      after RT. * RMH occur in almost half of the patients treated with RT. * RMH and
      RH are significantly more frequent in younger patients. * RH occur only in
      patients with RMH.

PMID- 29651772
TI  - Monitoring neurointerventional radiation doses using dose-tracking software:
      implications for the establishment of local diagnostic reference levels.
AB  - OBJECTIVES: There is potential for high radiation exposure during
      neurointerventional procedures. Increasing regulatory requirements mandate dose
      monitoring of patients and staff, and justification of high levels of radiation
      exposure. This paper demonstrates the potential to use radiation dose-tracking
      software to establish local diagnostic reference levels. METHODS: Consecutive
      neurointerventional procedures, performed in a single institution within a one
      year period, were retrospectively studied. Dose area product (DAP) data were
      collected using dose-tracking software and clinical data obtained from a
      prospectively generated patient treatment database. RESULTS: Two hundred and
      sixty-four procedures met the selection criteria. Median DAP was 100 Gy.cm2 for
      aneurysm coiling procedures, 259 Gy.cm2 for arteriovenous malformation (AVM)
      embolisation procedures, 87 Gy.cm2 for stroke thrombolysis/thrombectomy, and 74
      Gy.cm2 for four-vessel angiography. One hundred and nine aneurysm coiling
      procedures were further studied. Six significant variables were assessed using
      stepwise regression analysis to determine effect on DAP. Aneurysm location
      (anterior vs posterior circulation) had the single biggest effect (p = 0.004).
      CONCLUSIONS: This paper confirms variable radiation exposures during
      neurointerventional procedures. The 75th percentile (used to define diagnostic
      reference levels) of DAP measurements represents a reasonable guidance metric for
      monitoring purposes. Results indicate that aneurysm location has the greatest
      impact on dose during coiling procedures and that anterior and posterior
      circulation coiling procedures should have separate diagnostic reference levels.
      KEY POINTS: * Dose-tracking software is useful for monitoring patient radiation
      dose during neurointerventional procedures * This paper provides a template for
      methodology applicable to any interventional suite * Local diagnostic reference
      levels were defined by using the 75th percentile of DAP as per International
      Commission on Radiological Protection recommendations * Aneurysm location is the
      biggest determinant of radiation dose during coiling procedures. * Anterior and
      posterior circulation coiling procedures should have separate diagnostic
      reference levels.

PMID- 29651773
TI  - Complete genome sequence of peanut virus C, a putative novel ilarvirus.
AB  - We determined the complete genome sequence of a putative novel ilarvirus,
      tentatively named "peanut virus C" (PVC), identified in peanut (Arachis
      hypogaea). The three segmented genomic RNA molecules of PVC were 3474 (RNA1),
      2925 (RNA2), and 2160 (RNA3) nucleotides in length, with five predicted open
      reading frames containing conserved domains and motifs that are typical features
      of ilarviruses. The three genomic RNAs shared nucleotide sequence similarity (74%
      identity and 93% query coverage for RNA1, 75% identity and 85% query coverage for
      RNA2, and 72% identity and 70% query coverage for RNA3) with the most closely
      related ilarvirus, parietaria mottle virus. These results suggest that PVC is a
      novel member of the genus Ilarvirus in the family Bromoviridae.

PMID- 29651774
TI  - Genome editing for the treatment of tumorigenic viral infections and virus
      related carcinomas.
AB  - Viral infections cause at least 10%-15% of all human carcinomas. Over the last
      century, the elucidation of viral oncogenic roles in many cancer types has
      provided fundamental knowledge on carcinogenetic mechanisms and established a
      basis for the early intervention of virus-related cancers. Meanwhile, rapidly
      evolving genomeediting techniques targeting viral DNA/RNA have emerged as novel
      therapeutic strategies for treating virusrelated carcinogenesis and have begun
      showing promising results. This review discusses the recent advances of genome
      editing tools for treating tumorigenic viruses and their corresponding cancers,
      the challenges that must be overcome before clinically applying such genome
      editing technologies, and more importantly, the potential solutions to these
      challenges.

PMID- 29651776
TI  - Spillover Effects of Long-Term Disabilities on Close Family Members.
AB  - BACKGROUND: Care and support of people dealing with long-term disabilities
      involves the entire family. OBJECTIVE: This paper evaluates the effect of living
      with a relative dealing with a long-term disability on the health status of all
      family members in the household. METHODS: Using information from the Swiss
      household panel from the year 1999 to 2003 (n = 18,030), a linear regression is
      implemented to compare the health status of family members cohabiting with
      individuals dealing with a long-term disability with the health status of
      individuals of similar characteristics in the general population. Additionally, a
      non-parametric graphical analysis estimates the smooth patterns of the results
      over time. RESULTS: Family members who cohabit with a person dealing with a long
      term disability have a consistently reduced health status. The size of the impact
      depends on the sex and the role in the family. In general, women show the most
      negative effects. For children, the impact depends on the relationship with the
      disabled person. CONCLUSIONS: Recognizing the presence of health spillovers can
      help to design policies to better support families. Being the perceived health
      status a good indicator of the use of health services and mortality, the health
      system should focus on the entire family, and not only on the patient or the main
      caregiver.

PMID- 29651775
TI  - Characterization of hidden rules linking symptoms and selection of acupoint using
      an artificial neural network model.
AB  - Comprehension of the medical diagnoses of doctors and treatment of diseases is
      important to understand the underlying principle in selecting appropriate
      acupoints. The pattern recognition process that pertains to symptoms and diseases
      and informs acupuncture treatment in a clinical setting was explored. A total of
      232 clinical records were collected using a Charting Language program. The
      relationship between symptom information and selected acupoints was trained using
      an artificial neural network (ANN). A total of 11 hidden nodes with the highest
      average precision score were selected through a tenfold cross-validation. Our ANN
      model could predict the selected acupoints based on symptom and disease
      information with an average precision score of 0.865 (precision, 0.911; recall,
      0.811). This model is a useful tool for diagnostic classification or pattern
      recognition and for the prediction and modeling of acupuncture treatment based on
      clinical data obtained in a real-world setting. The relationship between symptoms
      and selected acupoints could be systematically characterized through knowledge
      discovery processes, such as pattern identification.

PMID- 29651777
TI  - Cost-effectiveness of Genome and Exome Sequencing in Children Diagnosed with
      Autism Spectrum Disorder.
AB  - BACKGROUND: Genome (GS) and exome sequencing (ES) could potentially identify
      pathogenic variants with greater sensitivity than chromosomal microarray (CMA) in
      autism spectrum disorder (ASD) but are costlier and result interpretation can be
      uncertain. Study objective was to compare the costs and outcomes of four genetic
      testing strategies in children with ASD. METHODS: A microsimulation model
      estimated the outcomes and costs (in societal and public payer perspectives in
      Ontario, Canada) of four genetic testing strategies: CMA for all, CMA for all
      followed by ES for those with negative CMA and syndromic features (CMA+ES), ES or
      GS for all. RESULTS: Compared to CMA, the incremental cost-effectiveness ratio
      (ICER) per additional child identified with rare pathogenic variants within 18
      months of ASD diagnosis was $CAN5997.8 for CMA+ES, $CAN13,504.2 for ES and
      $CAN10,784.5 for GS in the societal perspective. ICERs were sensitive to changes
      in ES or GS diagnostic yields, wait times for test results or pre-test genetic
      counselling, but were robust to changes in the ES or GS costs. CONCLUSION:
      Strategic integration of ES into ASD care could be a cost-effective strategy.
      Long wait times for genetic services and uncertain utility, both clinical and
      personal, of sequencing results could limit broader clinical implementation.

PMID- 29651778
TI  - Cost-Consequence Analysis Alongside a Randomised Controlled Trial of Hospital
      Versus Telephone Follow-Up after Treatment for Endometrial Cancer.
AB  - BACKGROUND: Regular outpatient follow-up programmes are usually offered to
      patients following treatment for gynaecological and other cancers. Despite the
      substantial resources involved in providing these programmes, there is evidence
      that routine follow-up programmes do not affect survival or the likelihood of
      detecting recurrence and may not meet patient needs. Alternative follow-up
      modalities may offer the same outcomes at lower cost. We examined the costs of
      using telephone-based routine follow-up of women treated for endometrial cancer
      undertaken by specialist gynaecology oncology nurses in comparison to routine
      hospital-based follow-up. METHODS: The ENDCAT trial randomised 259 women at five
      centres in the north west of England with a known diagnosis of Stage I
      endometrial cancer who had completed primary treatment on a 1:1 basis to receive
      either standard hospital outpatient follow-up or a telephone follow-up
      intervention administered by specialist nurses. A cost-consequence analysis was
      undertaken in which we compared costs to the health system and to individuals
      with the trial's co-primary outcomes of psychological morbidity and participant
      satisfaction with information received. RESULTS: Psychological morbidity,
      psychosocial needs, patient satisfaction and quality of life did not differ
      between arms. Patients randomised to telephone follow-up underwent more and
      longer consultations. There was no difference in total health service mean per
      patient costs at 6 months (mean difference L8, 95% percentile confidence
      interval: - L147 to L141) or 12 months (mean difference: - L77, 95% percentile
      confidence interval: - L334 to L154). Estimated return journey costs per patient
      for hospital consultations were L11.47. Productivity costs were approximately
      twice as high under hospital follow-up. CONCLUSION: Telephone follow-up was
      estimated to be cost-neutral for the NHS and may free up clinic time for other
      patients. There was some evidence that telephone follow-up may be more efficient
      for patients and wider society, and is not associated with additional
      psychological morbidity, lower patient satisfaction or reduced quality of life.
      TRIAL REGISTRATION: ISRCTN: 75220876, prospectively registered 28 October 2011.

PMID- 29651779
TI  - Out of Pocket Costs and Health Insurance Take-Up Rates.
AB  - BACKGROUND: Over the first ten years of this century, the share of the US
      population covered by employer-sponsored health insurance plans experienced a
      significant decline. A decrease in the take-up rate accounts for about a quarter
      of this decline. Usually, the increasing share of the premium that is paid by
      workers is used to explain the decline in the take-up rate. However, in recent
      years the increase in copayments, deductible and coinsurance rate has far
      outpaced the increase in worker contribution. OBJECTIVE: In this study we analyze
      the impact of out-of-pocket (OOP) costs, which consist of both workers'
      contribution toward the premium and expected expenditures, on the take-up rate
      for firms that offer multiple plan types. METHODS: Using data from the Employer
      Health Benefits Survey we estimated a pooled ordinary least squares and a fixed
      effects model. Since we have information about different types of health
      insurance plans offered by the firm, we derive the cross-price elasticity of
      coverage. RESULTS: Our fixed effects estimations suggest that workers respond to
      an increase in the out-of-pocket contributions for Health Maintenance
      Organization (HMO) plans by switching to PPO plans without impacting the overall
      take-up rate, while workers respond to increases in the out-of-pocket
      contribution for Preferred Provider Organization (PPO) plans by switching to HMO
      plans or dropping out of the group coverage. CONCLUSION: In general, we found
      that the estimated elasticities are too small to explain the overall drop in take
      up rates even in light of the large increases in required worker contributions
      and expected expenditures. Still, we highlight the growing importance of expected
      expenditures in explaining take-up rates.

PMID- 29651781
TI  - Abuse-Deterrent Opioid Formulations: A Key Ingredient in the Recipe to Prevent
      Opioid Disasters?
AB  - The US Food and Drug Administration (FDA) is encouraging the innovation of long
      acting opioid formulations that are manipulation-resistant. The purpose of this
      commentary is to assess the benefits and limitations of abuse-deterrent opioid
      formulations (ADFs) and discuss their role in mitigating the current opioid
      epidemic. ADFs have been created with chemical properties that make it difficult
      for people who non-medically use prescription drugs to crush and dissolve opioid
      tablets, as well as by combining opioids with antagonists such as naloxone or
      naltrexone, which are released only when the dosage form has been manipulated or
      the drug is taken by a non-intended route. Despite these and other technologies,
      consensus regarding the effectiveness of these formulations in preventing non
      medical use is lacking given the difficulty in obtaining post-marketing data.
      Researchers also question if the creation of abuse-deterrent drugs will have a
      positive effect on those struggling with a severe opioid-use disorder, fearing
      that current opioid users will simply find a new - perhaps more dangerous - drug
      of choice. Abuse-deterrent opioids are still opioids, and although they may make
      manipulation more difficult than non-ADF formulations, they are not "abuse
      proof." The introduction of ADFs could provide a false sense of security among
      prescribers and dispensers, and we fear that ADFs may have a minimal impact on
      non-medical use of prescription opioids. Further epidemiological studies will be
      required to determine the large-scale impact of abuse-deterrent opioids in
      preventing opioid use disorder and its downstream consequences.

PMID- 29651780
TI  - Sub-cellular markers highlight intracellular dynamics of membrane proteins in
      response to abiotic treatments in rice.
AB  - BACKGROUND: Cell biology approach using membrane protein markers tagged with
      fluorescent proteins highlights the dynamic behaviour of plant cell membranes,
      not only in the standard but also in changing environmental conditions. In the
      past, this strategy has been extensively developed in plant models such as
      Arabidopsis. RESULTS: Here, we generated a set of transgenic lines expressing
      membrane protein markers to extend this approach to rice, one of the most
      cultivated crop in the world and an emerging plant model. Lines expressing
      individually eight membrane protein markers including five aquaporins (OsPIP1;1,
      OsPIP2;4, OsPIP2;5, OsTIP1;1, OsTIP2;2) and three endosomal trafficking proteins
      (OsRab5a, OsGAP1, OsSCAMP1) were obtained. Importantly, we challenged in roots
      the aquaporin-expressing transgenic lines upon salt and osmotic stress and
      uncovered a highly dynamic behaviour of cell membrane. CONCLUSION: We have
      uncovered the relocalization and dynamics of plasma membrane aquaporins upon salt
      and osmotic stresses in rice. Importantly, our data support a model where
      relocalization of OsPIPs is concomitant with their high cycling dynamics.

PMID- 29651782
TI  - Erratum to: Early Life Hypoxic or Hypoxic/Hypercapnic Stress Alters Acute
      Ventilatory Sensitivity in Adult Mice.

PMID- 29651783
TI  - Unsolicited information letters to increase awareness of Lynch syndrome and
      familial colorectal cancer: reactions and attitudes.
AB  - Dissemination of information on a genetically increased risk should according to
      guidelines primarily be family-mediated. Incomplete and incorrect information
      spread has, however, been documented and implies missed possibilities for
      prevention. In Denmark, the national HNPCC register has been granted an exception
      to send unsolicited letters with information on hereditary colorectal cancer and
      an invitation to genetic counseling to members of families with familial and
      hereditary colorectal cancer. To evaluate this approach, we investigated
      reactions and attitudes to unsolicited letters in 708 members of families with
      genetic predisposition and in 1600 individuals from the general population.
      Support for information letters was expressed by 78% of the family members and by
      82% of the general population. Regarding route of information, 90% of family
      members preferred a letter to no information, 66% preferred information from the
      hospital rather than from family members and 40% preferred to obtain information
      from a close family member. Our results suggest that use of unsolicited
      information letters from the health care system may be a feasible and highly
      acceptable strategy to disseminate information to families at high risk of
      colorectal cancer.

PMID- 29651784
TI  - Are the effects of cognitive behavior therapy for severe fatigue in cancer
      survivors sustained up to 14 years after therapy?
AB  - PURPOSE: Cognitive behavior therapy (CBT) reduces cancer-related fatigue (CRF) in
      cancer survivors in the short term. We examined fatigue levels up to 14 years
      after CBT. METHODS: Eligible participants of two randomized controlled trials who
      had completed CBT for CRF and a post-treatment assessment were contacted (n =
      81). Fatigue was assessed with the subscale "fatigue severity" of the Checklist
      Individual Strength (CIS-fatigue). The course of fatigue over time was examined
      with linear mixed model analyses. Fatigue levels of participants were compared to
      matched population controls at long-term follow-up. We tested with multiple
      regression analysis if fatigue at follow-up was predicted by the patients'
      fatigue level and fatigue-perpetuating factors directly after CBT (post-CBT).
      RESULTS: Seventy-eight persons completed a follow-up assessment (response rate =
      96%, mean time after CBT = 10 years). The mean level of fatigue increased from
      23.7 (SD = 11.1) at post-CBT to 34.4 (SD = 12.4) at follow-up (p < 0.001).
      Population controls (M = 23,9, SD = 11.4) reported lower fatigue levels than
      participants. Half of the patients (52%) who were recovered from severe fatigue
      at post-CBT (CIS-fatigue < 35) were still recovered at long-term follow-up.
      Patients with lower fatigue levels at post-CBT were less likely to show relapse.
      CONCLUSION: Despite initial improvement after CBT, levels of fatigue deteriorated
      over time. Half of the patients who were recovered from severe fatigue after CBT
      still scored within normal ranges of fatigue at long-term follow-up. IMPLICATIONS
      FOR CANCER SURVIVORS: It should be explored how to help patients with a relapse
      of severe fatigue following an initially successful CBT. They may profit from CBT
      again, or another evidence-based intervention for fatigue (like mindfulness or
      exercise therapy). Future research to gain insight into reasons for relapse is
      warranted.

PMID- 29651785
TI  - Predicting Escitalopram Exposure to Breastfeeding Infants: Integrating Analytical
      and In Silico Techniques.
AB  - BACKGROUND: Escitalopram is used for post-partum depression; however, there are
      limited pharmacokinetic data of escitalopram in milk and plasma of infants
      breastfed by women taking the drug. OBJECTIVE: The objective of this study was to
      apply physiologically-based pharmacokinetic (PBPK) modelling to predict infant
      drug exposure (plasma area under the curve from time zero to infinity
      [AUCinfinity]) based on drug monitoring data of escitalopram in breast milk.
      METHODS: Using a newly developed liquid chromatography-tandem mass spectrometry
      (LC-MS/MS) method, we quantified escitalopram concentrations in milk samples of
      18 breastfeeding women with escitalopram therapy at steady state, collected at
      three to five time points. The escitalopram concentrations in breast milk were
      used with infant feeding parameters from the literature to simulate infant daily
      dose. We used PK-Sim(r) to develop an adult PBPK model for escitalopram and
      extrapolated it to a population of 1600 infants up to 12 months of age. An
      integration of the simulated infant daily dose and the virtual infants with
      variable physiological-pharmacological parameters was used to predict drug
      exposure (plasma AUCinfinity) distribution in the population of infants breastfed
      by women receiving escitalopram 20 mg/day. RESULTS: Escitalopram concentrations
      in milk were 50 +/- 17 ng/mL (mean +/- standard deviation). The simulated infant
      plasma AUCinfinity following escitalopram exposure through breast milk was low,
      with a median of 1.7% (range 0.5-5.9%) of the corresponding maternal plasma
      AUCinfinity, indicating no substantial exposure. CONCLUSIONS: Infant exposure
      levels to escitalopram in breast milk are low. A PBPK modeling approach can be
      used to translate data on drug monitoring in milk into a population distribution
      of infant plasma levels for drug safety assessment.

PMID- 29651787
TI  - Integrating geochemical investigations and geospatial assessment to understand
      the evolutionary process of hydrochemistry and groundwater quality in arid areas.
AB  - Groundwater is the key for life in arid areas. Aquifer overexploitation and
      climatic conditions can significantly deteriorate groundwater quality. The Al
      Qassim area in central Saudi Arabia is characterized by dense agricultural use
      and is irrigated mainly by fossil groundwater from the Saq Aquifer. Understanding
      the area's hydrochemistry, major factors governing groundwater quality, and
      alternative uses of the groundwater are the main goals of this study. Groundwater
      samples were collected and examined for major, minor, and trace elements. Ionic
      relationships, hydrochemical facies, geospatial distributions, and multivariate
      analyses were conducted to assess the hydrochemical processes at play. The
      salinity and nitrate concentrations of the Saq Aquifer's groundwater were found
      to increase in the outcrop areas more than the confined areas. The spatial
      distributions were fragmented by three main factors: (i) modern recharge by
      relatively brackish water, (ii) irrigation return flow in intensive farming
      areas, and (iii) overexploitation and draining of deep and relatively saline
      zones of the aquifer. Seven water types were found representing the alkaline
      water with a predominance of sulfate-chloride ions and earth alkaline water with
      a predominance of sulfate and chloride. Mixing between fresh and brackish water,
      dissolution of mineral phases, silicate weathering, and reverse ion exchange were
      recognized as the evolutionary processes, while evaporation played a minor role.
      Cluster analyses characterized the fresh groundwater zone, modern groundwater
      recharge zone, and anthropogenic influence zone. In the confined areas, nearly
      all the groundwater was appropriate for domestic use and irrigation. In the
      outcrop areas, some limitations were found due to unsuitable conditions.

PMID- 29651788
TI  - Sphincter-preserving surgery for recurrent pelvic malignancy using a hybrid
      procedure of open laparotomy and transanal endoscopic approach.
AB  - BACKGROUND: Surgery for the treatment of recurrent pelvic malignancy is
      challenging. Sphincter-preserving surgery (SPS) has been applied in limited
      cases. Transanal endoscopic approach (TEA) has been used for primary rectal
      cancer, predominantly for hybrid transabdominal-transanal total mesorectal
      excision. Here, we describe the use of TEA as a hybrid approach in a case of
      recurrent ovarian cancer. CASE PRESENTATION: A 59-year-old woman had recurrence
      of serous ovarian adenocarcinoma in the vaginal stump, near the site of
      anastomosis from a rectal resection 18 months previously. We used a hybrid
      approach comprising conventional open laparotomy and TEA to accomplish sphincter
      preservation. In addition to sphincter preservation, TEA allowed for the creation
      of a "terminal" space, which was made by anterior dissection between the rectum
      and the vagina. We employed TEA to create an opening in the scar tissue along the
      sacrum, which was used as a "guide" for pelvic dissection to prevent nerve
      injury. After exteriorization of the tumor, bowel continuity was achieved by hand
      sewn coloanal anastomosis with a protective diverting ileostomy. Pathological
      examination revealed no involvement of the surgical margins. The diverting
      ileostomy was taken down 8 months postoperatively. CONCLUSION: A hybrid approach
      comprising conventional open laparotomy and TEA allowed for safe and secure SPS
      and complete excision of a recurrent pelvic malignancy. This hybrid surgical
      approach expands the use of SPS in highly selected cases.

PMID- 29651789
TI  - Understanding Prosodic Focus Marking in Mandarin Chinese: Data from Children and
      Adults.
AB  - This study investigated whether Mandarin speakers interpret prosodic information
      as focus markers in a sentence-picture verification task. Previous production
      studies have shown that both Mandarin-speaking adults and Mandarin-speaking
      children mark focus by prosodic information (Ouyang and Kaiser in Lang Cogn
      Neurosc 30(1-2):57-72, 2014; Yang and Chen in Prosodic focus marking in Chinese
      four-and eight-year-olds, 2014). However, while prosodic focus marking did not
      seem to affect sentence comprehension in adults Mandarin-speaking children showed
      enhanced sentence comprehension when the sentence focus was marked by prosodic
      information in a previous study (Chen in Appl Psycholinguist 19(4):553-582,
      1998). The present study revisited this difference between Mandarin speaking
      adults and children by applying a newly designed task that tested the use of
      prosodic information to identify the sentence focus. No evidence was obtained
      that Mandarin-speaking children (as young as 3 years of age) adhered more
      strongly to prosodic information than adults but that word order was the
      strongest cue for their focus interpretation. Our findings support the view that
      children attune to the specific means of information structure marking in their
      ambient language at an early age.

PMID- 29651786
TI  - The why, when and how to test for obstructive sleep apnea in patients with atrial
      fibrillation.
AB  - Sleep apnea is associated with increased cardiovascular risk and may be important
      in atrial fibrillation (AF) management. It is present in up to 62% of the AF
      population and is highly under-recognized and underdiagnosed. Obstructive sleep
      apnea (OSA) is strongly associated with AF and non-randomized trials have shown
      that its treatment can help to reduce AF recurrences and maintain sinus rhythm.
      The 2016 European Society of Cardiology guidelines for the management of AF
      recommend that AF patients should be questioned regarding the symptoms of OSA and
      that OSA-treatment should be optimized to improve AF treatment results. However,
      strategies on how to implement OSA testing in the standard work-up of AF patients
      are not provided in the guidelines. Additionally, overnight OSA monitoring rather
      than interrogation for OSA-related clinical signs alone may be necessary to
      reliably identify OSA in the majority of AF patients. This review summarizes the
      available clinical data on OSA in AF patients, and discusses the following key
      questions: Why and When is testing for OSA needed in AF patients? How and Where
      should it be performed and coordinated? and Who should test for OSA? To implement
      OSA testing in a cardiology or electrophysiology clinic, we propose a
      multidisciplinary integrated care approach based on a chronic care model. We
      describe the tools, infrastructure and coordination needed to test for OSA in the
      standard workup of patients with symptomatic AF prior to the initiation of
      directed invasive or pharmacological rhythm control management.

PMID- 29651792
TI  - The plantaris muscle - rare relations to the neurovascular bundle in the
      popliteal fossa.
AB  - The plantaris muscle is characterized by morphological variability, both for
      origin and insertion, and may sometimes be absent. Its strength allows the
      ligament to be used for reconstruction of other tendons and ligaments. This
      report presents the rare placements and course of the plantaris muscle in
      relation to the neurovascular bundle. In this case, the hypertrophy of this
      muscle might cause pressure on the tibial nerve and produce symptoms similar to
      sciatica.

PMID- 29651790
TI  - Novel Insights for Inhibiting Mutant Heterodimer IDH1wt-R132H in Cancer: An In
      Silico Approach.
AB  - BACKGROUND: Isocitrate dehydrogenase 1 (IDH1) is a dimeric enzyme responsible for
      supplying the cell's nicotinamide adenine dinucleotide phosphate (NADPH) reserves
      via dehydrogenation of isocitrate (ICT) and reduction of NADP+. Mutations in
      position R132 trigger cancer by enabling IDH1 to produce D-2-hydroxyglutarate (2
      HG) and reduce inhibition by ICT. Mutant IDH1 can be found as a homodimer or a
      heterodimer. OBJECTIVE: We propose a novel strategy to inhibit IDH1 R132 variants
      as a means not to decrease the concentration of 2-HG but to provoke a cytotoxic
      effect, as the cell malignancy at this point no longer depends on 2-HG. We aim to
      inhibit the activity of the mutant heterodimer to block the wild-type subunit.
      Limiting the NADPH reserves in a cancerous cell will enhance its susceptibility
      to the oxidative stress provoked by chemotherapy. METHODS: We performed a virtual
      screening using all US FDA-approved drugs to replicate the loss of inhibition of
      mutant IDH1 by ICT. We characterized our results based on molecular interactions
      and correlated them with the described phenotypes. RESULTS: We replicated the
      loss of inhibition by ICT in mutant IDH1. We identified 20 drugs with the
      potential to inhibit the heterodimeric isoform. Six of them are used in cancer
      treatment. CONCLUSIONS: We present 20 FDA-approved drugs with the potential to
      inhibit IDH1 wild-type activity in mutated cells. We believe this work may
      provide important insights into current and new approaches to dealing with IDH1
      mutations. In addition, it may be used as a basis for additional studies centered
      on drugs presenting differential sensitivities to different IDH1 isoforms.

PMID- 29651793
TI  - Miratu'lEbdan Fi Tesrih-i Azaul-Insan: first printed illustrated anatomy book in
      Ottoman-Turkish medicine.
AB  - BACKGROUND: Medical education in Ottoman-Turkish medicine was shaped by the
      influence of Claudius Galenus (c.130-c.210) and Ibn-i Sina (c.980-c.1037). These
      teachings were performed in madrasahs until the beginning of the 19th century
      period. Within the scope of master-apprentice relationship, medical training was
      also given in private clinics. As a result of religious and social pressures on
      scientific studies human cadavers were never used because they were considered
      sacred. For centuries, all books were handwritten during the Ottoman Empire until
      the first printing press was established in Istanbul during 1726. However, the
      first illustrated book on anatomy was not printed until another 100 years later.
      MATERIALS AND METHODS: A comparative study was conducted on the anatomical
      drawings in"Miratu'l Ebdan Fi Tesrih-i Azau'l Insan" (Ataullah SM, 17th),and
      significance of this book. RESULTS: 46 out of 56 figures were received from the
      book of physian and anatomist Jean Palfin (1650-1730). Remaining 9 figures were
      cited from author himself as collected from Bernard Siegfried Albinus (1697
      1170), Raymond Vieussens (1614- 1715), R. Drake (1667-1707), Clopton Havers (1657
      1702), Albrecht von Haller (1708- 1777), Joseph Guichard Duverney (1648-1730).
      The figures were drawn exactly the same way with minimal changes. Main text of
      the book is mostly translation from Italian edition of Bertin and Palfin's
      Works.The book is not only the first printed anatomical book but also the first
      printed work in Ottoman-Turkish medicine. Another very significant aspect is the
      illustrations are perspective drawing figures which differs from miniature style
      drawings of the past. CONCLUSIONS: Sanizade Ataullah's work is a significant
      value not only for being the first printed illustrated anatomy book which makes
      it more approachable but also gives anatomical drawings as illustrations not as
      miniature style painting.

PMID- 29651791
TI  - A Discrete Event Simulation Model to Assess the Economic Value of a Hypothetical
      Pharmacogenomics Test for Statin-Induced Myopathy in Patients Initiating a Statin
      in Secondary Cardiovascular Prevention.
AB  - BACKGROUND: Statin (HMG-CoA reductase inhibitor) therapy is the mainstay
      dyslipidemia treatment and reduces the risk of a cardiovascular (CV) event (CVE)
      by up to 35%. However, adherence to statin therapy is poor. One reason patients
      discontinue statin therapy is musculoskeletal pain and the associated risk of
      rhabdomyolysis. Research is ongoing to develop a pharmacogenomics (PGx) test for
      statin-induced myopathy as an alternative to the current diagnosis method, which
      relies on creatine kinase levels. The potential economic value of a PGx test for
      statin-induced myopathy is unknown. METHODS: We developed a lifetime discrete
      event simulation (DES) model for patients 65 years of age initiating a statin
      after a first CVE consisting of either an acute myocardial infarction (AMI) or a
      stroke. The model evaluates the potential economic value of a hypothetical PGx
      test for diagnosing statin-induced myopathy. We have assessed the model over the
      spectrum of test sensitivity and specificity parameters. RESULTS: Our model
      showed that a strategy with a perfect PGx test had an incremental cost-utility
      ratio of 4273 Canadian dollars ($Can) per quality-adjusted life year (QALY). The
      probabilistic sensitivity analysis shows that when the payer willingness-to-pay
      per QALY reaches $Can12,000, the PGx strategy is favored in 90% of the model
      simulations. CONCLUSION: We found that a strategy favoring patients staying on
      statin therapy is cost effective even if patients maintained on statin are at
      risk of rhabdomyolysis. Our results are explained by the fact that statins are
      highly effective in reducing the CV risk in patients at high CV risk, and this
      benefit largely outweighs the risk of rhabdomyolysis.

PMID- 29651794
TI  - Celiac trunk and common hepatic artery variations in children: an analysis with
      CT angiography.
AB  - BACKGROUND: Understanding the celiac trunk and hepatic artery anatomy is
      important not only in preventing iatrogenic injuries but also in planning
      surgical procedures in children. Therefore, the aim of this study is to analyze
      the prevalence of celiac trunk (CeT) and common hepatic artery (CHA) variations
      in the pediatric population. MATERIALS AND METHODS: One hundred and seventy-four
      children (174) who underwent abdominal multidetector computed tomography (MDCT)
      angiography, either because of trauma or liver transplantation, were analyzed
      retrospectively. The patterns of CeT, CHA and their variant branches were
      revealed and compared with previous studies involving adults. RESULTS: A total of
      157 (90.2%) of the 174 patients had normal celiac trunk anatomy, whereas 17
      (9.8%) had variations. Five types of CeT variations were identified according to
      Song's classification in which 'Hepatosplenic trunk + Left gastric artery +
      Superior mesenteric artery' was the most prevalent. One hundred-twelve (64.4%) of
      the 174 patients had normal CHA anatomy; however 62 (35.6%) had variations. Six
      types of CHA variations were identified according to Michel's and Hiatt's
      classification. The most common was 'Replaced left hepatic artery originating
      from left gastric artery'. CONCLUSIONS: The prevalence of celiac trunk and
      hepatic artery variations are high in children as much as in their elders.
      Awareness of these variations by is important in terms of avoiding iatrogenic
      injury and in promoting surgical procedure planning for liver transplantation or
      abdominal tumor surgery.

PMID- 29651795
TI  - Variability of the vertebral artery origin and transverse foramen entrance level 
      CT angiographic study.
AB  - Vertebral artery (VA), the main element of the posterior brain circulation, has
      many anatomical variations which generally were widely investigated. However,
      available data vary in wide ranges, reflecting very different sample sizes, lack
      of data about left-right or sex differences, and about possible ethnic,
      regionally specific or genetic differences. Certain new findings suggest possible
      involvement of some environmental factors in VA variations. Accurate anatomical
      data about VA variations in different regions of the world, including Balkans
      countries, are still lacking. Therefore we investigated morphological variability
      of VA origin and its entrance level into cervical transverse foramina in
      population of Republika Srpska (Bosnia and Herzegovina), including data about the
      sex and side. Anatomy of VA was investigated in 112 persons (224 arteries) of
      both sexes (58 males, 54 females; age 19 - 83 years), using 64-slice CT scanner.
      Origin of VA from subclavian artery (SCA) we found in 95.08% of arteries (52
      males, 49 females). Only in one male (0.45 %) left VA and left SCA had an
      specific origin from aortic arch (AA), which we named as an "common area of
      origin". All other observed variations in origin were only of left VA,
      originating from AA in 4.47 % (5 males, 5 females). Left VA Most often (usual)
      entrance level into transverse foramen we found at C6 (87.5%), followed by C5
      (8.93 %), C4 (3.12 %), and in one case at level C7 (0.45 %). Entry levels at C5
      both, on right and on the left side, were 3 times more frequent in males than in
      females. Wide ranges of differences between the data we obtained on a sample in
      Republika Srpska (Bosnia and Herzegovina) and the data from many other studies
      require further and wider investigations.

PMID- 29651796
TI  - Oncological impact of neoadjuvant hormonal therapy on permanent iodine-125 seed
      brachytherapy in patients with low- and intermediate-risk prostate cancer.
AB  - OBJECTIVES: To determine whether neoadjuvant hormonal therapy improves
      oncological outcomes of patients with localized prostate cancer treated with
      permanent brachytherapy. METHODS: Between January 2004 and November 2014, 564
      patients underwent transperineal ultrasonography-guided permanent iodine-125 seed
      brachytherapy. We retrospectively analyzed low- or intermediate-risk prostate
      cancer based on the National Comprehensive Cancer Network guidelines. The
      clinical variables were evaluated for influence on biochemical recurrence-free
      survival, progression-free survival, cancer-specific survival and overall
      survival. RESULTS: A total of 484 patients with low-risk (259 patients) or
      intermediate-risk disease (225 patients) were evaluated. Of these, 188 received
      neoadjuvant hormonal therapy. With a median follow up of 71 months, the 5-year
      actuarial biochemical recurrence-free survival rates of patients who did and did
      not receive neoadjuvant hormonal therapy were 92.9% and 93.6%, respectively (P =
      0.2843). When patients were stratified by risk group, neoadjuvant hormonal
      therapy did not improve biochemical recurrence-free survival outcomes in low- (P
      = 0.8949) or intermediate-risk (P = 0.1989) patients. The duration or type of
      hormonal therapy was not significant in predicting biochemical recurrence. In a
      multivariate analysis, Gleason score, pretreatment prostate-specific antigen,
      clinical T stage, and prostate dosimetry, primary Gleason score and positive core
      rate were significant predictive factors of biochemical recurrence-free survival,
      whereas neoadjuvant hormonal therapy was insignificant. Furthermore, neoadjuvant
      hormonal therapy did not significantly influence progression-free survival,
      cancer-specific survival or overall survival. CONCLUSIONS: In patients with low-
      or intermediate-risk disease treated with permanent prostate brachytherapy,
      neoadjuvant hormonal therapy does not improve oncological outcomes. Its use
      should be restricted to patients who require prostate volume reduction.

PMID- 29651797
TI  - Pazopanib-induced crystal deposition in intestinal mucosa in a patient with
      retroperitoneal liposarcoma.
AB  - Pazopanib was administered to a 44-year-old man with local recurrence of
      retroperitoneal liposarcoma. Computed tomography showed an intestinal edema,
      which gradually progressed 15 months after pazopanib administration although he
      had no clinical symptoms. Upper gastrointestinal endoscopy implicated marked
      edematous hypertrophy of the Kerkling's fold. Pathological findings showed
      crystal deposition and fat accumulation, without a malignant component. All these
      abnormal findings resolved after pazopanib discontinuation.

PMID- 29651798
TI  - Long-term persistence with mirabegron in a real-world clinical setting.
AB  - OBJECTIVES: To examine the long-term persistence rate with mirabegron in a real
      world clinical setting. METHODS: We retrospectively collected the data of
      patients who were prescribed mirabegron. We investigated the persistence rate and
      the reason for the discontinuation. The analysis included patient's age,
      diagnosis, Overactive Bladder Symptom Score, prostatic volume, the prescription
      by specialists for lower urinary tract dysfunction, drug-naive patients,
      replacement of antimuscarinics or add-on therapy to antimuscarinics. RESULTS: A
      total of 556 patients were included. Among them, 401 patients (72%) had
      overactive bladder and the other 155 (28%) were categorized as having other
      storage symptoms. During the observation period, 170 patients (42%) with
      overactive bladder discontinued mirabegron. The reasons for discontinuation in
      patients with overactive bladder included unmet expectation of treatment (45
      patients, 26%), any adverse events (38 patients, 22%) or symptom improvement (37
      patients, 22%). The persistence or discontinuation was not related with age,
      Overactive Bladder Symptom Score, prostatic volume or the prescription by
      specialists, while older male patients tended to continue mirabegron. The 3-year
      persistence rates in female and male overactive bladder patients were 46% and
      51%, respectively, and these were better than those in patients with storage
      symptoms without urgency. In female overactive bladder patients, the persistence
      rate with mirabegron used as add-on therapy to antimuscarinics was higher than
      that in the drug-naive patients on the Kaplan-Meier curve. CONCLUSIONS: The
      present study shows a relatively good long-term persistence rate with mirabegron
      in overactive bladder patients, notwithstanding the retrospective study in an
      academic hospital. The combined treatment with antimuscarinics could result in a
      good persistence rate with mirabegron.

PMID- 29651799
TI  - Fatal cervicomediastinal necrotising fasciitis due to cholesteatoma.

PMID- 29651800
TI  - Caecal volvulus: a rare complication following a routine laparoscopic
      appendicectomy.

PMID- 29651801
TI  - Peritoneal encapsulation with an abnormal vessel in a band causing small bowel
      obstruction: a rare entity.

PMID- 29651803
TI  - Management of fungus balls as a result of Candida albicans.

PMID- 29651802
TI  - Three-months optical coherence tomography analysis of a biodegradable polymer,
      sirolimus-eluting stent.
AB  - OBJECTIVE: We aimed to assess early neointimal healing by optical coherence
      tomography (OCT) 3 months after implantation of the ultrathin Orsiro(r) sirolimus
      eluting stent with biodegradable polymer. BACKGROUND: New generations of drug
      eluting stents with biodegradable polymer have been developed to avoid the
      continued vascular irritation of durable polymers. METHODS: In this prospective,
      open-label study, 34 patients received an Orsiro(r) sirolimus-eluting stent with
      biodegradable polymer. In a subgroup of patients (n = 15), the intervention was
      performed under OCT guidance. All patients underwent OCT-examination at three
      months. The primary endpoint was 3-month neointimal healing (NIH) score,
      calculated by weighing the presence of filling defects, malapposed and uncovered
      struts. Secondary endpoint was maturity of tissue coverage at 3 months. RESULTS:
      At 3 months, NIH score was 13.7 (5.4-22), covered struts per lesion were 90% (84
      97%), malapposed struts were 2.7% (0.8-5.4%) and rate of mature tissue coverage
      was 47% (42-53%). No target lesion failure occurred up to 12 months. Patients
      with OCT-guided stent implantation demonstrated a trend toward earlier stent
      healing as demonstrated by superior NIH scores (angio guided: 17.6% [8.8-26.4];
      OCT-guided: 9.8% [4.0-15.5]; mean difference -8, [95%CI: -18.7-2.9], P = 0.123).
      This group had significantly more covered struts per lesion (angio-guided: 86%
      [82-90]; 95% [92-99]; mean difference 9% [95%CI: 3-15], P = 0.001). CONCLUSION:
      The Orsiro(r) sirolimus-eluting stent with biodegradable polymer shows early
      vascular healing with a high rate of strut coverage at 3-month follow-up. OCT
      guided stent implantation had a positive impact on early vascular healing.

PMID- 29651804
TI  - A complex-systems paradigm can lead to evidence-based policymaking and impactful
      action in substance misuse prevention-a rejoinder to Purshouse et al. (2018).

PMID- 29651805
TI  - Editorial Comment to Non-invasive assessment of kidney allograft fibrosis with
      shear wave elastography: A radiological-pathological correlation analysis.

PMID- 29651806
TI  - Therapeutic effect of propiverine hydrochloride on mixed-type urinary
      incontinence in women: The Female Urgency and Stress Urinary Incontinence Study
      of Propiverine Hydrochloride trial.
AB  - OBJECTIVES: To show the efficacy of propiverine hydrochloride in the management
      of symptoms of stress urinary incontinence in female patients with mixed-type
      urinary incontinence. METHODS: The study was carried out as a multicenter single
      arm clinical trial at 64 institutions in Japan. The participants were female
      patients aged >=20 years with mixed-type urinary incontinence. The frequency of
      stress urinary incontinence and urgency urinary incontinence was evaluated at
      baseline and 4, 8 and 12 weeks after treatment with propiverine hydrochloride.
      Subjective symptoms were evaluated using the Overactive Bladder Symptom Score and
      the International Consultation on Incontinence Questionnaire-Short Form.
      Functional urethral length and maximum urethral closing pressure were also
      measured at baseline and 12 weeks after treatment at the institutions where the
      urethral pressure profile was taken. RESULTS: In total, 49 mixed-type urinary
      incontinence patients were enrolled in the present study. The number of cases of
      urgency urinary incontinence was reduced time-dependently, which showed
      statistically significant differences between baseline and 4, 8 and 12 weeks
      after treatment. A similar statistically different reduction was also observed
      for stress urinary incontinence. The mean reduction rates of urgency urinary
      incontinence and stress urinary incontinence at 12 weeks after treatment were
      63.9% and 44.3%, respectively. The total scores of International Consultation on
      Incontinence Questionnaire-Short Form and Overactive Bladder Symptom Score were
      gradually reduced, and the differences were statistically significant. Functional
      urethral length and maximum urethral closing pressure at 12 weeks after treatment
      did not show any statistical differences compared with those at baseline.
      CONCLUSIONS: Propiverine hydrochloride can be an effective therapeutic option for
      stress urinary incontinence in patients with mixed-type urinary incontinence.

PMID- 29651807
TI  - Editorial Comment to Influence of prior oral ethinylestradiol use on the efficacy
      of enzalutamide for the treatment of castration-resistant prostate cancer in men.

PMID- 29651808
TI  - Editorial Comment to Prostate-specific antigen screening impacts on biochemical
      recurrence in patients with clinically localized prostate cancer.

PMID- 29651809
TI  - Development of chemotherapy and significance of conversion surgery after
      chemotherapy in unresectable pancreatic cancer.
AB  - While surgery currently remains the only potentially curative treatment available
      for pancreatic cancer, only 20% to 30% of patients have resectable disease at
      diagnosis. Recently, with the introduction of intensive chemotherapy regimens
      such as oxaliplatin, irinotecan, fluorouracil plus leucovorin (FOLFIRINOX) and
      gemcitabine plus nab-paclitaxel, for the treatment of unresectable pancreatic
      cancer, the antitumor activity and overall survival in patients with pancreatic
      cancer have dramatically improved. These advances in intensive chemotherapy have
      led to the possibility of conversion of unresectable disease to resectable
      disease, and it has been reported that more than 20% of pancreatic cancer
      patients with unresectable locally advanced disease at diagnosis undergo
      successful conversion surgery after FOLFIRINOX therapy. In metastatic pancreatic
      cancer, resection for the primary lesion of pancreatic cancer may show some
      benefits for some patients with complete resolution of metastases by
      chemotherapy. Furthermore, surgical resection in some patients with only a few
      metastases, so-called oligometastases, have also been reported. Conversion
      surgery is becoming increasingly possible with the introduction of intensive
      chemotherapies, however, the actual clinical benefits of resection in such cases
      has not yet been sufficiently investigated. The long-term safety, feasibility and
      outcomes still need to be investigated in well-designed, multi-institutional
      studies on a large number of patients.

PMID- 29651810
TI  - Recurrent stone-forming patients have high visceral fat ratio based on computed
      tomography images compared to first-time stone-forming patients.
AB  - OBJECTIVES: To compare various fat parameters based on computed tomography images
      between recurrent stone-forming patients and patients forming stones for the
      first time. METHODS: Included in the present study were 300 patients with upper
      urinary tract calculi who had undergone active stone removal in our hospital.
      Using pretreatment computed tomography images, we measured visceral fat area and
      volume, subcutaneous fat area and volume, visceral fat area ratio and visceral
      fat volume ratio. We compared patient backgrounds and these fat parameters
      between those who recurrently formed stones and those who formed stones for the
      first time. We also performed logistic regression analysis to identify factors
      that contribute to severe stones. RESULTS: A total of 148 (49.3%) patients were
      recurrent stone-forming patients. Recurrent stone-forming patients were
      statistically significantly younger (P < 0.01) and there were more male patients
      (P < 0.01). In addition, visceral fat area ratio and visceral fat volume ratio in
      recurrent stone-forming patients were significantly higher than those in first
      time stone-forming patients (P = 0.03 and P = 0.01, respectively). On the other
      hand, there was no significant difference in visceral fat area (P = 0.32),
      subcutaneous fat area (P = 0.36), visceral fat volume (P = 0.38) or subcutaneous
      fat volume (P = 0.23). Receiver operating characteristics analysis showed that
      area under the curve of visceral fat volume ratio (0.583) for recurrent stones
      was larger than that of visceral fat area ratio (0.571). In multivariate
      analysis, increasing visceral fat volume ratio was an independent significant
      predictor of recurrent stones (P = 0.04). CONCLUSIONS: Recurrent stone-forming
      patients have high visceral fat ratios compared to first-time stone-forming
      patients, shown here for the first time.

PMID- 29651811
TI  - Acute chylous peritonitis as a result of jejunal volvulus and small bowel
      obstruction from a congenital band adhesion.

PMID- 29651812
TI  - Editorial Comment to Intensity ratio curve analysis of small renal masses on T2
      weighted magnetic resonance imaging: Differentiation of fat-poor angiomyolipoma
      from renal cell carcinoma.

PMID- 29651814
TI  - Editorial Comment to Evaluating the predictive accuracy and the clinical benefit
      of a nomogram aimed to predict survival in node-positive prostate cancer
      patients: External validation on a multi-institutional database.

PMID- 29651813
TI  - Contralateral adrenal width predicts the duration of prolonged post-surgical
      steroid replacement for subclinical Cushing syndrome.
AB  - OBJECTIVES: To identify pre-treatment factors affecting the duration of post
      surgical steroid replacement in patients undergoing adrenalectomy for subclinical
      Cushing syndrome. METHODS: The present retrospective analysis included 64
      patients who underwent unilateral laparoscopic adrenalectomy for subclinical
      Cushing syndrome. Adrenal tumor and contralateral adrenal sizes together with
      various clinical factors were studied in association with the duration of post
      surgical steroid replacement. Adrenal tumor and contralateral adrenal size were
      measured at the level of the maximum transverse plane of the adrenal glands using
      computed tomography scan or magnetic resonance imaging. Cox's proportional
      hazards model was used for the statistical analysis. RESULTS: All 64 patients
      were treated with post-surgical steroid replacement after adrenalectomy. The
      median duration of the steroid treatment was 6 months. When assessing the
      duration of post-surgical steroid replacement, contralateral adrenal volume
      <0.745 cm3 , contralateral adrenal width <6.15 mm and serum cortisol after a 1-mg
      dexamethasone suppression test >2.65 MUg/dL were significant predictors of
      prolonged post-surgical steroid treatment on univariate analysis. On multivariate
      analysis, contralateral adrenal width <6.15 mm was the only independent
      predictive factor for the prolonged post-surgical steroid replacement.
      CONCLUSIONS: Contralateral adrenal width seems to represent a significant
      predictive factor for the duration of post-surgical steroid replacement in
      subclinical Cushing syndrome patients. Pre-surgical assessment of image findings
      might help clinicians determine the total duration of steroid therapy after
      adrenalectomy.

PMID- 29651815
TI  - 23rd Meeting of the ESNCH: Book of Abstracts, Prague, Czech Republic, April 13
      16, 2018.

PMID- 29651816
TI  - Theoretical and hands-on guidance from dental hygienists promotes good oral
      health in elderly people living in nursing homes, a pilot study.
AB  - OBJECTIVES: Oral health in nursing homes for elderly is often unsatisfactory, and
      oral health education to nursing staff has not shown sufficient results why there
      is need for novel approaches. The aim of the study was to trial a new oral
      healthcare educational programme and to evaluate the effects on residents' oral
      health. In addition, attitudes among the nursing staff in the intervention
      nursing home were explored. METHODS: In a controlled clinical trial, two
      comparable nursing homes were randomly assigned for intervention or control.
      Interventions included weekly theoretical and hands-on guidance from dental
      hygienists on oral hygiene procedures and discussions on oral care routines. The
      residents' oral health, measured by the Revised Oral Assessment Guide (ROAG),
      dental plaque and gingival bleeding were evaluated at baseline and after 3
      months. Attitudes among the staff to oral health care were measured at the
      intervention nursing home. RESULTS: Revised Oral Assessment Guide gums and lips
      scores showed a tendency to decrease in the intervention group, but remained high
      in the control group. Plaque levels improved significantly after intervention,
      and a trend towards less gingival bleeding was observed. The intervention nursing
      staff seemed to be more aware of their own limitations concerning oral health
      care after intervention and valued more frequent contact with dental services to
      a greater extent. CONCLUSIONS: The oral healthcare situation for elderly people
      today is so complex that theoretical education at the group level regarding
      different aspects of oral health is not sufficient. Individual hands-on guidance
      by dental hygienists on a regular basis in everyday care may be a new approach.

PMID- 29651817
TI  - Two Cases of Chloromethylisothiazolinone and Methylisothiazolinone-associated
      Toxic Lung Injury.
AB  - Previous animal studies have not conclusively determined the association between
      exposure to humidifier disinfectants (HDs) containing 5-chloro-2-methyl-4
      isothiazolin-3-one (CMIT) and/or 2-methyl-4-isothiazolin-3-one (MIT) and
      development of HD-associated lung injuries. Nonetheless, patients exposed to HDs
      containing only CMIT and/or MIT showed clinically similar lung injuries to those
      exposed to HDs containing polyhexamethylene guanidine (PHMG) or oligo (2-[2
      ethoxy]ethoxyethyl) guanidinium chloride (PGH). Here, we report twin sisters with
      lung injuries associated with exposure to CMIT/MIT-containing HDs. At 6 months of
      age, a younger twin sister presented with the 3-day history of cough, sputum, and
      respiratory difficulty. Chest radiography revealed multiple patchy consolidation
      and ground-glass opacities with pneumothorax and pneumomediastinum. Thoracostomy
      was performed due to pneumothorax at admission and she was discharged at 11 days
      of hospitalization. At 5 years of age, multiple tiny nodules and faint
      centrilobular ground-glass opacities were observed with the small pneumatocele.
      The elder sister visited a tertiary hospital due to dyspnea at 12 months of age.
      Chest radiography showed consolidation, pneumomediastinum, and pulmonary
      interstitial emphysema. There was no response to the administration of
      immunosuppressant drugs and antifibrotic agents. At 5 years of age, chest CT
      revealed ground-glass opacity and multiple tiny centrilobular ground-glass
      opacities nodules in both lungs with exercise intolerance.

PMID- 29651818
TI  - Effects on Periocular Tissues after Proton Beam Radiation Therapy for Intraocular
      Tumors.
AB  - BACKGROUND: To present our experience on orbital and periorbital tissue changes
      after proton beam radiation therapy (PBRT) in patients with intraocular tumors,
      apart from treatment outcomes and disease control. METHODS: Medical records of 6
      patients with intraocular tumors who had been treated with PBRT and referred to
      oculoplasty clinics of two medical centers (Seoul National University Hospital
      and Seoul Metropolitan Government-Seoul National University Boramae Medical
      Center) from October 2007 to September 2014 were retrospectively reviewed. The
      types of adverse effects associated with PBRT, their management, and progression
      were analyzed. In anophthalmic patients who eventually underwent enucleation
      after PBRT due to disease progression, orbital volume (OV) was assessed from
      magnetic resonance (MR) images using the Pinnacle3 program. RESULTS: Among the
      six patients with PBRT history, three had uveal melanoma, and three children had
      retinoblastoma. Two eyes were treated with PBRT only, while the other four eyes
      ultimately underwent enucleation. Two eyes with PBRT only suffered from radiation
      dermatitis and intractable epiphora due to canaliculitis or punctal obstruction.
      All four anophthalmic patients showed severe enophthalmic features with
      periorbital hollowness. OV analysis showed that the difference between both
      orbits was less than 0.1 cm before enucleation, but increased to more than 2 cm3
      after enucleation. CONCLUSION: PBRT for intraocular tumors can induce various
      orbital and periorbital tissue changes. More specifically, when enucleation is
      performed after PBRT due to disease progression, significant enophthalmos and OV
      decrease can develop and can cause poor facial cosmesis as treatment sequelae.

PMID- 29651819
TI  - Biochemical Predictors of Early Onset Non-Alcoholic Fatty Liver Disease in Young
      Children with Obesity.
AB  - BACKGROUND: The prevalence of metabolic syndrome (MS) and non-alcoholic fatty
      liver disease (NAFLD) and their associated risk factors are not well-established
      in young children with obesity. The purpose of this study was to evaluate the
      prevalence of early onset NAFLD and identify its biochemical predictors in obese
      children aged less than 10 years. METHODS: Anthropometric measurements, blood
      pressure, laboratory tests, and abdominal ultrasonography (USG) were performed in
      all subjects. National Cholesterol Education Program-Adult Treatment Panel III
      (NCEP-ATP III) criteria for MS diagnosis and liver enzymes and USG for NAFLD
      diagnosis were assessed. RESULTS: A total of 356 children with obesity (233 boys,
      123 girls) were included, with 172 children age <= 10 years and 184 adolescents.
      The prevalence of MS was 23.3% in young children and 35.3% in adolescents (P =
      0.020); while the prevalence of NAFLD was 36.0% and 70.7%, respectively (P =
      0.001). In obese children aged 10 years or less, there were significant
      differences in levels of serum gamma-glutamyltranspeptidase (gammaGT) (P <
      0.001), triglycerides (P = 0.042), and homeostatic model assessment of insulin
      resistance (P < 0.001) between the non-NAFLD and the NAFLD group. Multivariate
      logistic regression analysis revealed significant increase in serum gammaGT and
      uric acid levels in young children. CONCLUSION: Although MS and NAFLD were more
      prevalent in adolescents, young children also demonstrated MS and NAFLD as
      obesity-related complications. Elevated serum gammaGT and uric acid levels may
      serve as biochemical predictors in detecting NAFLD in young children with obesity
      before investigation with abdominal USG.

PMID- 29651820
TI  - Seroprevalence of Opsonophagocytic Antibodies against Serotype Ia, Ib, II, III,
      and V Group B Streptococcus among Korean Population.
AB  - BACKGROUND: Invasive Streptococcus agalactiae (group B streptococcus, GBS)
      infection most commonly occurs in infants; however, cases of GBS infection in
      adults, particularly in the elderly with significant underlying diseases, are
      being increasingly reported. We analyzed the serotype specific opsonophagocytic
      antibodies (the major mechanism of protection against GBS) in infants, adults,
      and the elderly. METHODS: The opsonization indices (OIs) of antibodies against
      serotype Ia, Ib, II, III, and V GBS were studied in 89 infants, 35 adults (age,
      30-50 years), and 62 elderly individuals (age, 65-85 years) according to the
      University of Alabama at Birmingham GBS opsonophagocytic killing assay protocol
      (www.vaccine.uab.edu). RESULTS: In infants, adults, and elderly groups
      respectively, geometric mean of OI against GBS serotype Ia were 3, 7, and 32;
      against GBS serotype Ib were 7, 242, and 252; against serotype II were 93, 363,
      and 676; against serotype III were 8, 212, and 609; and against serotype V were
      4, 639, and 610. The seropositive rate (% of subjects with OI >= 4) increased
      significantly in older age group for all five serotypes. CONCLUSION: During
      infancy, only a limited proportion of infants have functional immunity against
      serotype Ia, Ib, II, III, and V GBS. Furthermore, a lack of opsonic activities
      against GBS observed in some adults and the elderly might predispose such
      individuals to the risk of invasive GBS infection. Epidemiological monitoring and
      development of suitable vaccine for these populations are needed.

PMID- 29651822
TI  - Importance of Functional Assessment of Immunity against Group B Streptococcus.

PMID- 29651821
TI  - Exploratory Factor Analysis of the Beck Anxiety Inventory and the Beck Depression
      Inventory-II in a Psychiatric Outpatient Population.
AB  - BACKGROUND: To further understand the relationship between anxiety and
      depression, this study examined the factor structure of the combined items from
      two validated measures for anxiety and depression. METHODS: The participants were
      406 patients with mixed psychiatric diagnoses including anxiety and depressive
      disorders from a psychiatric outpatient unit at a university-affiliated medical
      center. Responses of the Beck Anxiety Inventory (BAI), Beck Depression Inventory
      (BDI)-II, and Symptom Checklist-90-Revised (SCL-90-R) were analyzed. We conducted
      an exploratory factor analysis of 42 items from the BAI and BDI-II. Correlational
      analyses were performed between subscale scores of the SCL-90-R and factors
      derived from the factor analysis. Scores of individual items of the BAI and BDI
      II were also compared between groups of anxiety disorder (n = 185) and depressive
      disorder (n = 123). RESULTS: Exploratory factor analysis revealed the following
      five factors explaining 56.2% of the total variance: somatic anxiety (factor 1),
      cognitive depression (factor 2), somatic depression (factor 3), subjective
      anxiety (factor 4), and autonomic anxiety (factor 5). The depression group had
      significantly higher scores for 12 items on the BDI while the anxiety group
      demonstrated higher scores for six items on the BAI. CONCLUSION: Our results
      suggest that anxiety and depressive symptoms as measured by the BAI and BDI-II
      can be empirically differentiated and that particularly items of the cognitive
      domain in depression and those of physical domain in anxiety are noteworthy.

PMID- 29651823
TI  - Weak light emission of soft tissues induced by heating.
AB  - The main goal of this work is to show that soft tissue interaction with high
      intensity focused ultrasound (HIFU) or direct heating leads to a weak light
      emission detectable using a small animal optical imaging system. Our results show
      that the luminescence signal is detectable after 30 min of heating, resembling
      the time scale of delayed luminescence. The imaging of a soft tissue after
      heating it using an HIFU field shows that the luminescence pattern closely
      matches the shape of the cone typical of the HIFU beam. We conclude that heating
      a soft tissue using two different sources leads to the emission of a weak
      luminescence signal from the heated region with a decay half-life of a few
      minutes (4 to 6 min). The origin of such light emission needs to be further
      investigated.

PMID- 29651824
TI  - Effect of optical aberrations on intraocular pressure measurements using a
      microscale optical implant in ex vivo rabbit eyes.
AB  - Elevated intraocular pressure (IOP) is the only modifiable major risk factor of
      glaucoma. Recently, accurate and continuous IOP monitoring has been demonstrated
      in vivo using an implantable sensor based on optical resonance with remote
      optical readout to improve patient outcomes. Here, we investigate the
      relationship between optical aberrations of ex vivo rabbit eyes and the
      performance of the IOP sensor using a custom-built setup integrated with a Shack
      Hartmann sensor. The sensor readouts became less accurate as the aberrations
      increased in magnitude, but they remained within the clinically acceptable range.
      For root-mean-square wavefront errors of 0.10 to 0.94  MUm, the accuracy and the
      signal-to-noise ratio were 0.58  +/-  0.32  mm Hg and 15.57  +/-  4.85  dB,
      respectively.

PMID- 29651826
TI  - New percutaneous interventions in heart failure.
AB  - Chronic heart failure (HF) is one of the main causes of mortality and morbidity
      worldwide and represents a growing challenge in interventional cardiology. Its
      prevalence is recently increasing due to the improvements in cardiac care with
      subsequent significant reduction in the HF acute mortality. HF may occur with
      either a reduced left ventricular ejection fraction (LVEF) (LVEF<40%, HFrEF) or a
      preserved EF (typically LVEF>=50%, HFpEF) indicative of diastolic dysfunction.
      Despite recent advances in drug therapies as well as in nonpharmacological
      strategies, including defibrillators, cardiac resynchronization therapy, LV
      assist devices (LVAD), mortality in HF remains high. New transcatheter
      implantable devices have been developed to improve the treatment of chronic HF.
      In this review we will summarize data on interventional HF devices that are
      currently approved or under investigation including treatment alternatives for
      mitral (MR) and tricuspid regurgitation (TR), left ventricle restoration through
      partitioning devices and left atrial decompression with shunting devices.

PMID- 29651825
TI  - Feasibility of using optical coherence tomography to detect acute radiation
      induced esophageal damage in small animal models.
AB  - Lung cancer survival is poor, and radiation therapy patients often suffer serious
      treatment side effects. The esophagus is particularly sensitive leading to acute
      radiation-induced esophageal damage (ARIED). We investigated the feasibility of
      optical coherence tomography (OCT) for minimally invasive imaging of the
      esophagus with high resolution (10  MUm) to detect ARIED in mice. Thirty mice
      underwent cone-beam computed tomography imaging for initial setup assessment and
      dose planning followed by a single-dose delivery of 4.0, 10.0, 16.0, and 20.0 Gy
      on 5.0-mm spots, spaced 10.0 mm apart in the esophagus. They were repeatedly
      imaged using OCT up to three months postirradiation. We compared OCT findings
      with histopathology obtained three months postirradiation qualitatively and
      quantitatively using the contrast-to-background-noise ratio (CNR). Histopathology
      mostly showed inflammatory infiltration and edema at higher doses; OCT findings
      were in agreement with most of the histopathological reports. We were able to
      identify the ARIED on OCT as a change in tissue scattering and layer thickness.
      Our statistical analysis showed significant difference between the CNR values of
      healthy tissue, edema, and inflammatory infiltration. Overall, the average CNR
      for inflammatory infiltration and edema damages was 1.6-fold higher and 1.6-fold
      lower than for the healthy esophageal wall, respectively. Our results showed the
      potential role of OCT to detect and monitor the ARIED in mice, which may
      translate to humans.

PMID- 29651827
TI  - Influence of pharmacokinetic/pharmacodynamic ratio on vancomycin treatment
      response in paediatric patients with Staphylococcus aureus bacteremia.
AB  - BACKGROUND: Staphylococcus aureus is a frequent cause of hospital-acquired
      bacteremia in paediatrics patients. Vancomycin is the drug of choice for the
      treatment of methicillin-resistant strains, although treatment failure is
      frequently observed. Area under the curve (AUC) of plasma concentrations over the
      minimum inhibitory concentration (MIC) has been proposed as the best index to
      predict treatment response, although information about its clinical impact on
      paediatric patients is scarce. The objective of this study is to determine if
      early recovery of an AUC/MIC>400 mg*h/L for vancomycin in paediatric patients
      with S. aureus bacteremia is associated with clinical and microbiological
      treatment response. METHODS: Retrospective observational study. Paediatric
      patients younger than 3 years with vancomycin-treated S. aureus bacteremia were
      included. The pharmacokinetic parameters were calculated from the vancomycin
      value obtained in the first 72 hours of treatment, assuming a bicompartmental
      model. A multivariate analysis was performed to analyze factors associated with
      early clinical response, treatment failure, microbiological response and 30-day
      mortality. RESULTS: 51 patients with S. aureus bacteremia were included in the
      study. In 18 patients (35.3%), strains with a MIC higher than 1.0 mg/L were
      isolated, being in eight (15.7%) greater than 1.5 mg/L. 22 (43.1%) patients did
      not reach an estimated AUC/MIC>400 during the first 72 hours. A significant
      association was observed between attainment of an AUC/MIC>400 and early clinical
      response [OR:3.23(95%CI:1.07-12.03)]. No significant association was found
      between an AUC/MIC>400 and microbiological response or mortality. CONCLUSIONS: An
      AUC/MIC>400 is associated with early response to vancomycin in paediatric
      patients with S. aureus bacteremia.

PMID- 29651828
TI  - Long term survival of a pediatric patient affected with atelosteogenesis type 3
      in an adult intensive care unit.

PMID- 29651829
TI  - Incidental finding of an Xq microdeletion in a girl with Trichorhinophalangeal
      Syndrome Type I harboring a novel TRPS1 Nonsense mutation.

PMID- 29651830
TI  - Qualitative and quantitative revaluation of specific learning disabilities: a
      multicentric study.
AB  - BACKGROUND: Specific learning disabilities are disorders that affect the
      instrumental skills of academic learning, leaving intact the general intellectual
      functioning. It is possible to distinguish: dyslexia, dysorthography, dysgraphia,
      and dyscalculia. The diagnosis is made according to DSMV. The aim of this study
      is to evaluate the implementation of Law N degrees  170 following a diagnosis of
      specific learning disabilities in children and their evolution over time.
      METHODS: The sample under examination consists of 75 children, 56 males and 18
      females aged 7,8 to 16 years, with a diagnosis of specific learning disabilities;
      a revaluation was carried outthrough the use of standardized instruments
      according to age and school attended. A twopart questionnaire was proposed: the
      first part turned to the parents/carers of the child and the second part turned
      to the boy himself. The improvement parameter has been linked, through a
      statistical analysis of univarianza with intelligence quotient, age, application
      of the law 10 October 2010 n 170, rehabilitative paths and attending afterschool
      program. RESULTS: Most of the guys are followed at school by the application of
      the law 170 and, outside school, by attending speech and neuropsychological
      therapy and after school. Going to investigate the actual use of the measures put
      in place by the school, it is evident a partial and incomplete application of Law
      170. CONCLUSIONS: The most suitable measures for these children are pedagogical
      measures in order to make them integrate with the group class and strengthen
      their capacities through specific measures provided by a specific legislative
      decree.

PMID- 29651831
TI  - Does age affect outcome in children with clavicle fracture treated
      conservatively? QuickDash and MRC evaluation of 131 consecutive cases.
AB  - BACKGROUND: Non-operative treatment with immobilization is the gold-standard for
      paediatric clavicular fractures. Purpose of this study is to evaluate functional
      outcomes and efficacy of non-operative treatment of clavicular fractures in a
      succession of 131 children. METHODS: Between 2006 and 2012, we treated non
      surgically 131 children for a clavicular fracture. All fractures have been
      classified according to Robinson classification. Clavicle shortening, range of
      movements and muscular strength through the Medical Research Council (MRC) scale
      were evaluated. To assess the outcomes, QuickDASH questionnaire, dividing the
      sample in 3 age-related group, was administered. RESULTS: The average follow-up
      was 26 months (8-84 months). Clavicle shortening at the time of injury occurred
      in 18 cases. All fractures reached union. Average time to union was 34 days. Mean
      time return to activity was 12.6 weeks. No cases of nonunion or delayed union
      were reported. Complications occurred in 21 cases. A shortening persisted in 2
      cases. Only one patient had a slight functional restriction. Average QuickDASH
      score was 6.2+/-1.1 (range 4.3-9.4). All patients recovered to a MRC score of 5,
      except for one patient with a score of 4. Best QuickDASH scores were observed in
      the group aged under 8 years and in non-comminuted and lateral third fractures of
      the clavicle. CONCLUSIONS: Observing results, clavicle fractures have a
      satisfactory clinical healing as shown by the good scores at QuickDASH and MRC
      scale. Younger children under 8 years can achieve the best results with a
      conservative treatment in terms of bone healing and activity level.

PMID- 29651832
TI  - Psychological wellbeing in parents of children with phenylketonuria and
      association with treatment adherence.
AB  - BACKGROUND: Phenylketonuria (PKU) is a rare metabolic disorder that leads to
      severe neurological abnormalities unless early treated with a strict
      phenylalanine (Phe)-restricted diet. The parents' involvement in PKU management
      is crucial and could lead to psychological distress; however, few studies have
      explored the parents' psychological wellbeing. The study aimed to: 1) evaluate
      the presence of psychological distress and impaired quality of life among parents
      of children with PKU, assessing the load of the diagnosis and the load of the
      treatment management; 2) explore the associations with their children's blood-Phe
      levels. METHODS: 138 parents of patients with PKU (who need a Phe-restricted
      diet) and with a mild form (mild hyperphenylalaninemia-MHP, with no diet
      indication) filled-out self-report psychological questionnaires; Phe-levels of
      children with PKU were retrieved. RESULTS: Parents of children with PKU did not
      report higher levels of psychological distress neither compared with the
      normative scores nor with parents of children with MHP. Optimal Phe- levels were
      associated with a higher number of parents' depressive complaints, with a lower
      tendency to express anger feelings, with a lower Social functioning, and a higher
      Mental health. CONCLUSIONS: Parents of children with PKU showed a good
      psychological adaptation to their children's disease and treatment. Findings
      highlighted associations between parents' psychological wellbeing and their
      children's adherence to diet. Interestingly, an optimal adherence to the diet of
      their children was associated with parental low social functioning, a higher
      tendency to control the anger expression, and greater somatic depressive
      symptoms.

PMID- 29651833
TI  - Growth recovery in newly arrived international adoptees in Italy: relation to
      parenting stress.
AB  - BACKGROUND: Following initial adversities, most internationally adopted children
      arrive with significant growth delays. Post-placement recovery has been widely
      documented, but research about risk or protective factors is still limited. Even
      less is known about the relationship between growth recovery and the quality of
      the family environment. METHODS: 28 children in 26 adoptive families were
      involved in this longitudinal study. A comprehensive evaluation (including
      anthropometry, cognitive assessment [using the Leiter International Performance
      Scale-Revised], and completion by both parents of the Parenting Stress Index -
      Short Form) was done at arrival of the child, and 1 year later. RESULTS: Results
      evidenced that on arrival nearly half of children had growth measurements in the
      normal range. All the children showed a significant recovery in height and weight
      at 6 and 12 months post-placement. Initial and follow up growth measurements
      correlated strongly. Growth recovery was related to the age of the child at
      adoption, the proportion of time the child had resided in institutional care, as
      well as parenting stress. Results suggested that the higher the parenting stress
      experienced the less improvements occurred in children: for mothers for height
      and weight, for fathers for all the growth indicators. CONCLUSIONS: Results
      suggested the critical importance of family factor in influencing children's
      growth recovery.

PMID- 29651835
TI  - Use of a probiotic mixture containing Bifidobacterium animalis subsp. lactis BB12
      and Enterococcus faecium L3 in atopic children.
AB  - BACKGROUND: Imbalance of the human gut microbiota in childhood, mainly due to low
      gut biodiversity and a low bifidobacterial load, has been suggested as a risk
      factor for atopy. Administration of Enterococcus faecium L3 in infants has been
      shown to increase the gut bifidobacterial count. The aim was to verify if a
      mixture of Bifidobacterium animalis subsp. lactis BB12 and E. faecium L3 could
      reduce the signs, symptoms and need for drugs in atopic children. METHODS: We
      retrospectively analyzed, and compared with controls, clinical outcomes following
      use of BB12 and L3 strains when administered 3 months before or during the
      development of signs and symptoms of atopy. RESULTS: When administered in the 3
      months before the development of atopy, the BB12 and L3 strains significantly
      reduced (P<0.001) rhinitis, watery eyes and cough/bronchospasm. However, reduced
      efficacy was observed when the mixture was given during the 3 months of atopy.
      The mixture of strains also significantly reduced the use of oral antihistamines,
      inhaled corticosteroids (in the same children in two different years) and oral
      corticosteroids (in different children in the same year). CONCLUSIONS: When
      administered as a prophylactic, the mixture of BB12 and L3 (iNatal Ped(r))
      statistically decreases the signs and symptoms of atopy and reduces the use of
      drugs. Administration of the same probiotics as treatment after the appearance of
      atopy is less effective.

PMID- 29651834
TI  - Efficacy of anthropometric measures for identifying cardiovascular disease risk
      in adolescents: review and meta-analysis.
AB  - INTRODUCTION: To compare the ability of Body Mass Index (BMI), waist
      circumference (WC) and waist to height ratio (WHtR) to estimate cardiovascular
      disease (CVD) risk levels in adolescents. EVIDENCE ACQUISITION: A systematic
      review and meta-analysis was performed after a database search for relevant
      literature (Cochrane, Centre for Review and Dissemination, PubMed, British
      Nursing Index, CINAHL, BIOSIS citation index, ChildData, metaRegister). EVIDENCE
      SYNTHESIS: The study included 117 records representing 96 studies with 994,595
      participants were included in the systematic review, 14 of which (13 studies,
      N.=14,610) were eligible for the meta-analysis. The results of the meta-analysis
      showed that BMI was a strong indicator of systolic blood pressure, diastolic
      blood pressure, triglycerides, high-density lipoprotein cholesterol and insulin;
      but not total cholesterol, low-density lipoprotein or glucose. Few studies were
      eligible for inclusion in the meta-analysis considering WC or WHtR (N.<=2). The
      narrative synthesis found measures of central adiposity to be consistently valid
      indicators of the same risk factors as BMI. CONCLUSIONS: BMI was an indicator of
      CVD risk. WC and WHtR were efficacious for indicating the same risk factors BMI
      performed strongly for, though there was insufficient evidence to judge the
      relative strength of each measure possibly due to heterogeneity in the methods
      for measuring and classifying WC.

PMID- 29651836
TI  - Near-Infrared Light-Activated Thermosensitive Liposomes as Efficient Agents for
      Photothermal and Antibiotic Synergistic Therapy of Bacterial Biofilm.
AB  - Biofilm is closely related to chronic infections and is difficult to eradicate.
      Development of effective therapy strategies to control biofilm infection is still
      challenging. Aiming at biofilm architecture, we designed and prepared near
      infrared-activated thermosensitive liposomes with photothermal and antibiotic
      synergistic therapy capacity to eliminate Pseudomonas aeruginosa biofilm. The
      liposomes with positive charge and small size aided to enter the biofilm
      microchannels and locally released antibiotics in infection site. The liposomes
      could remain stable at 37  degrees C and release about 80% antibiotics over 45 
      degrees C. The biofilm dispersion rate was up to 80%, which was a 7- to 8-fold
      rise compared to excess antibiotic alone, indicating that the localized
      antibiotic release and photothermal co-therapy improved the antimicrobial
      efficiency. In vivo drug-loaded liposomes in treating P. aeruginosa-induced
      abscess exhibited an outstanding therapeutic effect. Furthermore, photothermal
      treatment could stimulate the expression of bcl2-associated athanogene 3 to
      prevent normal tissue from thermal damage. The near-infrared-activated
      nanoparticle carriers had the tremendous therapeutic potential to dramatically
      enhance the efficacy of antibiotics through thermos-triggered drug release and
      photothermal therapy.

PMID- 29651837
TI  - Synthesis of 2-Aminopyridines via a Base-Promoted Cascade Reaction of N
      Propargylic beta-Enaminones with Formamides.
AB  - N-Substituted formamides as nucleophiles react with in situ-generated 1,4
      oxazepines from N-propargylic beta-enaminones followed by spontaneous N
      deformylation to deliver densely substituted 2-aminopyridines in good yields (31
      88%). The formyl group is found to be a superior traceless activating group of
      free amines and would ultimately be removed in situ. This reaction proceeds
      smoothly at room temperature, in the presence of NaOH as sole additive, without
      protection from the atmosphere and generates H2O and sodium formate as
      byproducts.

PMID- 29651839
TI  - Functionalization Pattern of Graphene Oxide Sheets Controls Entry or Produces
      Lipid Turmoil in Phospholipid Membranes.
AB  - Molecular dynamics, coarse-grained to the level of hydrophobic and hydrophilic
      interactions, shows that graphene oxide sheets, GOSs, can pierce through the
      phospholipid membrane and navigate the double layer only if the hydrophilic
      groups are randomly dispersed in the structure. Their behavior resembles that
      found in similar calculations for pristine graphene sheets. If the oxidation is
      located at the edge of the sheets, GOSs hover over the membrane and trigger a
      major reorganization of the lipids. The reorganization is the largest when the
      radius of the edge-functionalized sheet is similar to the length of the
      lipophilic chain of the lipids. In the reorganization, the heads of the lipid
      chains form dynamical structures that pictorially resemble the swirl of water
      flowing down a drain. All effects maximize the interaction between hydrophobic
      moieties on the one hand and lipophilic fragments on the other and are
      accompanied by a large number of lipid flip-flops. Possible biological
      consequences are discussed.

PMID- 29651838
TI  - Analysis and Identification of 2'-Deoxyadenosine-Derived Adducts in Lung and
      Liver DNA of F-344 Rats Treated with the Tobacco-Specific Carcinogen 4
      (Methylnitrosamino)-1-(3-pyridyl)-1-butanone and Enantiomers of its Metabolite 4
      (Methylnitrosamino)-1-(3-pyridyl)-1-butanol.
AB  - 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and its metabolite 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) are carcinogenic in animal
      models and are believed to play an important role in human lung carcinogenesis
      for cigarette smokers. Cytochrome P450-mediated metabolism of these tobacco
      specific nitrosamines produces reactive species that alkylate DNA in the form of
      pyridyloxobutyl (POB)- or pyridylhydroxybutyl (PHB)-DNA adducts. Understanding
      the formation mechanism and overall levels of these adducts can potentially
      enhance cancer prevention methods through the identification of particularly
      susceptible smokers. Previous studies have identified and measured a panel of POB
      and PHB-DNA base adducts of dGuo, dCyd, and Thd; however, dAdo adducts have yet
      to be determined. In this study, we complete this DNA adduct panel by identifying
      and quantifying levels of NNK- and NNAL-derived dAdo adducts in vitro and in
      vivo. To accomplish this, we synthesized standards for expected dAdo-derived DNA
      adducts and used isotope-dilution LC-ESI+-MS/MS to identify POB adducts formed in
      vitro from the reaction of 4-(acetoxymethylnitrosamino)-1-(3-pyridyl)-1-butanone
      (NNKOAc) with calf thymus DNA. Adduct levels were then quantified in lung and
      liver DNA of rats chronically treated with NNK or NNAL for 50 weeks using similar
      LC-MS detection methods. The in vitro studies identified N6-POB-dAdo and N1-POB
      dIno as products of the reaction of NNKOAc with DNA, which supports our proposed
      mechanism of formation. Though both N6-dAdo and N1-dIno adducts were found in
      vitro, only N6-dAdo adducts were found in vivo, implying possible intervention by
      DNA repair mechanisms. Analogous to previous studies, levels of N6-POB-dAdo and
      N6-PHB-dAdo varied both with tissue and treatment type. Despite the adduct levels
      being relatively modest compared to most other POB- and PHB-DNA adducts, they may
      play a biological role and could be used in future studies as NNK- and NNAL
      specific DNA damage biomarkers.

PMID- 29651840
TI  - Glucosamine-Based Supramolecular Nanotubes for Human Mesenchymal Cell Therapy.
AB  - Herein, we demonstrate an example of glucosamine-based supramolecular hydrogels
      that can be used for human mesenchymal cell therapy. We designed and synthesized
      a series of amino acid derivatives based on a strategy of capping d-glucosamine
      moiety at the C-terminus and fluorinated benzyl group at the N-terminus. From a
      systematic study on chemical structures, we discovered that the glucosamine-based
      supramolecular hydrogel [pentafluorobenzyl (PFB)-F-Glu] self-assembled with one
      dimensional nanotubular structures at physiological pH. The self-assembly of a
      newly discovered PFB-F-Glu motif is attributed to the synergistic effect of pi-pi
      stacking and extensive intermolecular hydrogen bonding network in aqueous medium.
      Notably, PFB-F-Glu nanotubes are proven to be nontoxic to human mesenchymal stem
      cells (hMSCs) and have been shown to enhance hMSC proliferation while maintaining
      their pluripotency. Retaining of pluripotency capabilities provides potentially
      unlimited source of undifferentiated cells for the treatment of future cell
      therapies. Furthermore, hMSCs cultured on PFB-F-Glu are able to secrete paracrine
      factors that downregulate profibrotic gene expression in lipopolysaccharide
      treated human skin fibroblasts, which demonstrates that PFB-F-Glu nanotubes have
      the potential to be used for wound healing applications. Overall, this article
      addresses the importance of chemical design to generate supramolecular
      biomaterials for stem cell therapy.

PMID- 29651841
TI  - Flexible and Compressible PEDOT:PSS@Melamine Conductive Sponge Prepared via One
      Step Dip Coating as Piezoresistive Pressure Sensor for Human Motion Detection.
AB  - Flexible and wearable pressure sensor may offer convenient, timely, and portable
      solutions to human motion detection, yet it is a challenge to develop cost
      effective materials for pressure sensor with high compressibility and
      sensitivity. Herein, a cost-efficient and scalable approach is reported to
      prepare a highly flexible and compressible conductive sponge for piezoresistive
      pressure sensor. The conductive sponge, poly(3,4
      ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS)@melamine sponge (MS),
      is prepared by one-step dip coating the commercial melamine sponge (MS) in an
      aqueous dispersion of poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate)
      (PEDOT:PSS). Due to the interconnected porous structure of MS, the conductive
      PEDOT:PSS@MS has a high compressibility and a stable piezoresistive response at
      the compressive strain up to 80%, as well as good reproducibility over 1000
      cycles. Thereafter, versatile pressure sensors fabricated using the conductive
      PEDOT:PSS@MS sponges are attached to the different parts of human body; the
      capabilities of these devices to detect a variety of human motions including
      speaking, finger bending, elbow bending, and walking are evaluated. Furthermore,
      prototype tactile sensory array based on these pressure sensors is demonstrated.

PMID- 29651842
TI  - Oritavancin Retains a High Affinity for a Vancomycin-Resistant Cell-Wall
      Precursor via Its Bivalent Motifs of Interaction.
AB  - Despite its potent antibacterial activities against drug-resistant Gram-positive
      pathogens, oritavancin remains partially understood with respect to its primary
      mode of hydrogen bond interaction with a cell-wall peptide regarding the role of
      its lipophilic 4'-chlorobiphenyl moiety. Here we report a surface plasmon
      resonance (SPR) study performed in two cell-wall model surfaces, each prepared by
      immobilization with a vancomycin-susceptible Lys-d-Ala-d-Ala or vancomycin
      resistant Lys-d-Ala-d-Lac peptide. Analysis of binding kinetics performed on the
      peptide surface showed that oritavancin bound ~100-1000-fold more tightly than
      vancomycin on each model surface. Ligand competition experiments conducted by SPR
      and fluorescence spectroscopy provided evidence that such affinity enhancement
      can be attributed to its 4'-chlorobiphenyl moiety, possibly through a hydrophobic
      interaction that led to a gain of free energy with a contribution from enthalpy
      as suggested by a variable-temperature SPR experiment. On the basis of these
      findings, we propose a model for the bivalent motifs of interaction of
      oritavancin with cell-wall peptides, by which the drug molecule can retain a
      strong interaction even with the vancomycin-resistant peptide. In summary, this
      study advances our understanding of oritavancin and offers new insight into the
      significance of bivalent motifs in the design of glycopeptide antibiotics.

PMID- 29651843
TI  - Tunable Resonance Coupling in Single Si Nanoparticle-Monolayer WS2 Structures.
AB  - Two-dimensional semiconducting transition metal dichalcogenides (TMDCs) are
      extremely attractive materials for optoelectronic applications in the visible and
      near-infrared range. Coupling these materials to optical nanocavities enables
      advanced quantum optics and nanophotonic devices. Here, we address the issue of
      resonance coupling in hybrid exciton-polariton structures based on single Si
      nanoparticles (NPs) coupled to monolayer (1L)-WS2. We predict a strong coupling
      regime with a Rabi splitting energy exceeding 110 meV for a Si NP covered by 1L
      WS2 at the magnetic optical Mie resonance because of the symmetry of the mode.
      Further, we achieve a large enhancement in the Rabi splitting energy up to 208
      meV by changing the surrounding dielectric material from air to water. The
      prediction is based on the experimental estimation of TMDC dipole moment
      variation obtained from the measured photoluminescence spectra of 1L-WS2 in
      different solvents. An ability of such a system to tune the resonance coupling is
      realized experimentally for optically resonant spherical Si NPs placed on 1L-WS2.
      The Rabi splitting energy obtained for this scenario increases from 49.6 to 86.6
      meV after replacing air by water. Our findings pave the way to develop high
      efficiency optoelectronic, nanophotonic, and quantum optical devices.

PMID- 29651844
TI  - Strategy for Comprehensive Identification of Acylcarnitines Based on Liquid
      Chromatography-High-Resolution Mass Spectrometry.
AB  - Carnitines play important roles in fatty acid oxidation and branched chain amino
      acid metabolism. The disturbance of acylcarnitines is associated with occurrence
      and development of many diseases. Comprehensive acylcarnitine identification can
      greatly benefit their targeted detection, following disease differential
      diagnosis and possible mechanism study. In this study, we developed a novel
      strategy to identify as many acylcarnitines as possible based on liquid
      chromatography-high-resolution mass spectrometry (LC-HRMS). The layer-layer
      progressive strategy first integrated the initial full scan MS/data-dependent
      MS/MS monitoring (ddMS2) acquisition and the following parallel reaction
      monitoring (PRM) to analyze a pooled biological sample. Also 733 possible
      acylcarnitines were identified containing characteristic high-resolution MS/MS
      features. Further, accurate mass, retention rules, and HRMS/MS information were
      used to define subclasses and predict undetected acylcarnitine homologues in each
      subclass, leading to more acylcarnitines to our newly constructed database. As a
      result, 758 acylcarnitines were contained in the database, having exact mass,
      retention time, and MS/MS information, which is the most comprehensive list of
      acylcarnitines reported to date. Applying this database, 241, 515, and 222
      acylcarnitines were rapidly and reliably annotated in human plasma, human urine,
      and rat liver tissue. This novel strategy enables large-scale identification of
      acylcarnitines, and a similar method can also be used for identification of other
      metabolites.

PMID- 29651845
TI  - Accurate Measurement of Formaldehyde-Induced DNA-Protein Cross-Links by High
      Resolution Orbitrap Mass Spectrometry.
AB  - Genomic instability caused by DNA-protein cross-link (DPCs)-induced DNA damage is
      implicated in disease pathogenesis, aging, and cancer development. The covalent
      linkages between DNA and protein are induced by chemical reactions catalyzed by
      the endogenous metabolic intermediates and exogenous agents, such as aldehydes,
      chemotherapeutic agents, and ionizing radiation. Formaldehyde has been classified
      as a genotoxic carcinogen. In addition, endogenous formaldehyde-induced DPCs may
      increase the risks of bone marrow toxicity and leukemia. There is a need to
      develop an effective detection method for DPC analysis, including the structural
      differentiation of endogenous and exogenous formaldehyde-induced DPCs. To this
      end, our group previously reported a useful liquid chromatography-selected
      reaction monitoring (LC-SRM) approach coupled with stable isotope labeling and
      low mass resolution-triple quadrupole mass spectrometry. In the present work, we
      further demonstrate an accurate quantification method using a high-resolution,
      accurate-mass Orbitrap mass spectrometer for the measurement of the covalent
      linkage between 2'-deoxyguanosine (dG) and cysteine (Cys), specifically termed dG
      Me-Cys, one kind of linkages derived from the formaldehyde-induced DPCs. This
      quantification method with a wide dynamic range of at least 3 orders generates an
      interference-free spectrum for unbiased and unambiguous quantification, resulting
      in good intra- and interday precisions and accuracies with less than 10%
      variations. The endogenous and exogenous amounts of dG-Me-Cys in a human cell
      line treated with formaldehyde are analyzed by our new methodology. The
      quantification strategy demonstrated in this study can be widely applied to
      characterize and quantify other DPC linkages induced by formaldehyde or other
      chemical agents.

PMID- 29651846
TI  - pH-Signaling Transcription Factor AopacC Regulates Ochratoxin A Biosynthesis in
      Aspergillus ochraceus.
AB  - In Aspergillus and Penicillium species, an essential pH-response transcription
      factor pacC is involved in growth, pathogenicity, and toxigenicity. To
      investigate the connection between ochratoxin A (OTA) biosynthesis and ambient
      pH, the AopacC in Aspergillus ochraceus was functionally characterized using a
      loss-of-function mutant. The mycelium growth was inhibited under pH 4.5 and 10.0,
      while the sporulation increased under alkaline condition. A reduction of mycelium
      growth and an elevation of sporulation was observed in Delta AopacC mutant.
      Compared to neutral condition, OTA contents were respectively reduced by 71.6 and
      79.8% under acidic and alkaline conditions. The expression of AopacC increased
      with the elevated pH, and deleting AopacC dramatically decreased OTA production
      and biosynthetic genes Aopks expression. Additionally, the Delta AopacC mutant
      exhibited attenuated infection ability toward pear fruits. These results suggest
      that AopacC is an alkaline-induced regulator responsible for growth and OTA
      biosynthesis in A. ochraceus and this regulatory mechanism might be pH-dependent.

PMID- 29651847
TI  - Labeling Carboxyl Groups of Surface-Exposed Proteins Provides an Orthogonal
      Approach for Cell Surface Isolation.
AB  - Quantitative profiling of cell surface proteins is critically important for the
      understanding of cell-cell communication, signaling, tissue development, and
      homeostasis. Traditional proteomics methods are challenging for cell surface
      proteins due to their hydrophobic nature and low abundance, necessitating
      alternative methods to efficiently identify and quantify this protein group. Here
      we established carboxyl-reactive biotinylation for selective and efficient
      biotinylation and isolation of surface-exposed proteins of living cells. We
      assessed the efficiency of carboxyl-reactive biotinylation for plasma membrane
      proteins by comparing it with a well-established protocol, amine-reactive
      biotinylation, using SILAC (stable isotope labeling in cell culture). Our results
      show that carboxyl-reactive biotinylation of cell surface proteins is both more
      selective and more efficient than amine-reactive biotinylation. We conclude that
      it is a useful approach, which is partially orthogonal to amine-reactive
      biotinylation, allowing us to cast a wider net for a comprehensive profiling of
      cell surface proteins.

PMID- 29651848
TI  - Mass-Spectrometry-Based Identification of Cross-Links in Proteins Exposed to
      Photo-Oxidation and Peroxyl Radicals Using 18O Labeling and Optimized Tandem Mass
      Spectrometry Fragmentation.
AB  - Protein cross-links are formed in regulated biochemical processes in many
      biological systems, but they are also generated inadvertently via the reactions
      of exogenous or endogenous oxidants. Site-specific identification and
      characterization of such cross-links is challenging, and the goal was, therefore,
      to develop mass-spectrometry-based approaches tailored for proteins subjected to
      oxidative challenges that also are applicable for the analysis of complex
      samples. Using trypsin-mediated 18O isotopic labeling, different types of data
      acquisition workflows, and designated database software tools, we successfully
      identified tyrosine-tyrosine, tyrosine-tryptophan, tyrosine-lysine, and histidine
      lysine cross-links in proteins subjected to sensitizer-mediated photo-oxidation
      with rose bengal or chemical oxidation with peroxyl radicals generated from the
      water-soluble compound 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH).
      Subsequently, AAPH was also applied to a protein extract from the Gram-positive
      bacterium Lactococcus lactis, demonstrating the feasibility to identify tyrosine
      tyrosine, tyrosine-tryptophan, and tryptophan-tryptophan cross-linked peptides in
      a complex system. Different fragmentation techniques were evaluated, and it was
      observed that higher-energy collisional dissociation (HCD) resulted in a higher
      number of identified cross-link peptides, while electron-transfer dissociation
      supplemented with HCD (EThcD) generally provides higher fragment ion coverage of
      the cross-linked peptides.

PMID- 29651849
TI  - Improved Synthesis of 4-Cyanotryptophan and Other Tryptophan Analogues in Aqueous
      Solvent Using Variants of TrpB from Thermotoga maritima.
AB  - The use of enzymes has become increasingly widespread in synthesis as chemists
      strive to reduce their reliance on organic solvents in favor of more
      environmentally benign aqueous media. With this in mind, we previously endeavored
      to engineer the tryptophan synthase beta-subunit (TrpB) for production of
      noncanonical amino acids that had previously been synthesized through multistep
      routes involving water-sensitive reagents. This enzymatic platform proved
      effective for the synthesis of analogues of the amino acid tryptophan (Trp),
      which are frequently used in pharmaceutical synthesis as well as chemical
      biology. However, certain valuable compounds, such as the blue fluorescent amino
      acid 4-cyanotryptophan (4-CN-Trp), could only be made in low yield, even at
      elevated temperature (75  degrees C). Here, we describe the engineering of TrpB
      from Thermotoga maritima that improved synthesis of 4-CN-Trp from 24% to 78%
      yield. Remarkably, although the final enzyme maintains high thermostability ( T50
      = 93  degrees C), its temperature profile is shifted such that high reactivity is
      observed at ~37  degrees C (76% yield), creating the possibility for in vivo 4-CN
      Trp production. The improvements are not specific to 4-CN-Trp; a boost in
      activity at lower temperature is also demonstrated for other Trp analogues.

PMID- 29651850
TI  - Exploring the Potential of a Global Emerging Contaminant Early Warning Network
      through the Use of Retrospective Suspect Screening with High-Resolution Mass
      Spectrometry.
AB  - A key challenge in the environmental and exposure sciences is to establish
      experimental evidence of the role of chemical exposure in human and environmental
      systems. High resolution and accurate tandem mass spectrometry (HRMS) is
      increasingly being used for the analysis of environmental samples. One lauded
      benefit of HRMS is the possibility to retrospectively process data for
      (previously omitted) compounds that has led to the archiving of HRMS data.
      Archived HRMS data affords the possibility of exploiting historical data to
      rapidly and effectively establish the temporal and spatial occurrence of newly
      identified contaminants through retrospective suspect screening. We propose to
      establish a global emerging contaminant early warning network to rapidly assess
      the spatial and temporal distribution of contaminants of emerging concern in
      environmental samples through performing retrospective analysis on HRMS data. The
      effectiveness of such a network is demonstrated through a pilot study, where
      eight reference laboratories with available archived HRMS data retrospectively
      screened data acquired from aqueous environmental samples collected in 14
      countries on 3 different continents. The widespread spatial occurrence of several
      surfactants (e.g., polyethylene glycols ( PEGs ) and C12AEO-PEGs ),
      transformation products of selected drugs (e.g., gabapentin-lactam, metoprolol
      acid, carbamazepine-10-hydroxy, omeprazole-4-hydroxy-sulfide, and 2-benzothiazole
      sulfonic-acid), and industrial chemicals (3-nitrobenzenesulfonate and bisphenol
      S) was revealed. Obtaining identifications of increased reliability through
      retrospective suspect screening is challenging, and recommendations for dealing
      with issues such as broad chromatographic peaks, data acquisition, and
      sensitivity are provided.

PMID- 29651851
TI  - PATIENT SATISFACTION AFTER BREAST RECONSTRUCTION: IMPLANTS VS. AUTOLOGOUS
      TISSUES.
AB  - INTRODUCTION: Breast reconstruction is increasingly present in the treatment of
      breast cancer. It may be accomplished with implants or autologous tissues. This
      cross-sectional study evaluates patients satisfaction and quality of life in
      women after successful autologous or implant breast reconstruction. MATERIAL AND
      METHODS: 109 women who successfully underwent breast reconstruction between 2007
      and 2016 were included. The patients completed the BREAST-Q questionnaire at
      follow-up visits. Additional data were collected retrospectively from the
      hospital charts regarding complications, smoking, chemotherapy, radiotherapy,
      unilateral or bilateral reconstruction, BMI and comorbidities. Mann-Whitney U
      Test was applied to evaluate differences between the autologous breast
      reconstruction group (n = 50) and the implant breast reconstruction group (n =
      59). RESULTS: Women with a successful autologous reconstruction were
      significantly more satisfied with their reconstructed breasts than women with
      successful alloplastic breast reconstruction as measured by the BREAST-Q breasts
      module (p = 0. 00596), psycho-social well-being module (p=0.04) and sexual well
      being module (p=0.00068). Furthermore, there is a higher degree of satisfaction
      in patients who have not undergone radiotherapy, with no complications and with a
      normal BMI for implant reconstruction group as well as in non-smokers, and
      bilateral reconstructions for flap reconstruction group. DISCUSSION: The findings
      of our study are in agreement with the data found in the literature, attributing
      greater satisfaction with physical, mental and social wellbeing, as well as with
      elements having repercussion on sexual wellbeing, to autologous breast
      reconstruction. CONCLUSIONS: Autologous breast reconstruction leads to higher
      patient satisfaction than implant breast reconstruction. This study may help
      patients and medical teams in their decision-making process regarding breast
      reconstruction. This pilot study opens several questions that need further
      investigations in a larger prospective studyKeywords: Breast reconstruction,
      breast-Q, satisfaction, implant, autologous tissue.

PMID- 29651852
TI  - CURRENT TREATMENT OPTIONS OF DUPUYTREN'S DISEASE.
AB  - Dupuytren's disease (fibromatosis of the palmar fascia, benign neoplastic
      fibromatosis, Dupuytren's contracture) is a disease characterized by growth and
      successive contracture of single parts of the palmar aponeurosis. This condition
      is known and has been treated for several centuries. In the advanced stages of
      the disease, it leads to significant limitation of hand function, resulting in
      reduced quality of life of the patient. Dupuytren's disease (DD) is a life-long
      disease with a variable course and a heterogeneous clinical presentation. Therapy
      focuses on the clinical manifestations of the disease as well as on reduction of
      the functional limitation of the hand caused by the disease. In addition to
      conservative and surgical procedures, there are also some mini-invasive methods
      available. Treatment should be reserved for centres and experienced surgeons
      specialized in hand surgery.

PMID- 29651853
TI  - OLEOGEL-S10 TO ACCELERATE HEALING OF DONOR SITES: MONOCENTRIC RESULTS OF PHASE
      III CLINICAL TRIAL.
AB  - MATERIAL AND METHODS: Oleogel-S10, an ointment containing betulin-rich triterpene
      dry extract from birch bark was tested in an open, blindly evaluated,
      prospective, controlled, randomized multicentre study to improve wound healing in
      donor sites. The primary endpoint was time to wound closure, and secondary
      endpoints were scar related measurements at the time of wound closure, and 3 and
      12 months after wound closure (POSAS, laser speckle contrast analysis,
      viscoelastic analysis). RESULTS: We report the results from a single centre
      (Department of Burns and Reconstructive Surgery, University Hospital Brno) of
      this phase III clinical trial. A total of 32 patients (25 men and 7 women) were
      included with the mean patient age of 41.8 years (SD, +/-11.66). The mean extent
      of patients donor sites in the study was 56.77cm2 (SD, +/-20.39). Median healing
      time of the verum group (Oleogel-S10) was 7 days (95% Confidence Interval 7-8
      days) and for controls 8 days (95% CI 7-10 days). Comparison of POSAS data from
      the verum group revealed significantly lower values at all three time points as
      compared to the controls. Perfusion of scars of the verum group reached on
      average of 115 perfusion units at the end of treatment; the average was 69.8
      perfusion units at the 3-month follow-up and 50.2 perfusion units at the 12-month
      follow-up. Control sites displayed significantly higher values at all time points
      (122.2 perfusion units, 73.9 perfusion units, 52.2 perfusion units). Significant
      differences were detected in the skins viscoelastic properties, with sites
      treated with Oleogel-S10 displaying more favourable values. CONCLUSION: In our
      results, we demonstrate the significant effectiveness of Oleogel-S10 in donor
      sites healingKeywords: Donor site, Triterpenes, Oleogel-S10, wound closure.

PMID- 29651854
TI  - THE NASOLABIAL FLAP: THE MOST VERSATILE METHOD IN FACIAL RECONSTRUCTION.
AB  - The nasolabial flap was described 170 years ago and still remains one of the most
      frequently used methods in facial reconstruction. This technically easy and
      maximally effective procedure has become a real workhorse and an integral
      instrument for every plastic surgeon. Over time multiple modifications of this
      technique have been described. In this article, authors present an overview of
      nasolabial flap modalities and discuss advantages and disadvantages of these
      techniques.

PMID- 29651855
TI  - SURGICAL TREATMENT OF MELANOMA.
AB  - Malignant melanoma is a serious disease, the incidence of which rises. Since the
      most important treatment method is sufficient wide skin and subcutaneous tissue
      excision, plastic surgeon is often the only specialist who is able to close the
      resulting defect. This paper deals with recommendations and treatment options for
      malignant melanoma from the point of a plastic surgeon. The primary width of
      excised safety rim of healthy tissue with regards to the depth of melanoma
      invasion differs. Safety margin is 0.5 cm for melanoma in situ, 1 cm in Breslow
      up to 2 mm and 2 cm in Breslow over 2 mm. Furthermore, there is indication for
      sentinel lymph node biopsy, which should be performed in melanoma with Breslow
      over 1 mm, and in risky melanoma in Breslow above 0.75 mm. Every patient with
      stage IIB malignant melanoma and above according to TNM classification should
      undergo adjuvant therapy in a specialized centre. Ideal condition for the patient
      is a permanent and close cooperation between a dermatologist, oncologist and
      plastic surgeon, who supplement each other in diagnostics, therapy and follow up
      of the patients.

PMID- 29651856
TI  - POSTOPERATIVE FIXATION AFTER REPOSITIONING OF PREMAXILLA IN A PATIENT WITH
      BILATERAL CLEFT LIP AND PALATE - CASE REPORT.
AB  - This article presents orthodontic-surgical treatment in an eight-year-old patient
      with bilateral cleft lip and palate where premaxilla was surgically repositioned
      in the mixed dentition stage. By cranial and dorsal insertion of the premaxilla
      were created satisfactory occlusal relationship for ongoing eruption of permanent
      teeth, together with functional lip closure, improved pronunciation and a
      positive change in appearance of the centrofacial area. Reposition of premaxilla
      was associated with bilateral alveolar bone grafting of the cleft defect with
      cancellous bone from the iliac crest. Based on the model surgery were prepared
      rigid orthodontic wires, which ensured postoperative fixation of the segments of
      the upper jaw. The patient was wearing band fixed appliance for another 6 months
      after surgery. Healing was uncomplicated, the new position of the premaxilla was
      stable and more physiological. This procedure was friendly for a child patient
      and did not require fixation of the jaw segments by Sauer splint.

PMID- 29651857
TI  - Physical and Physiological Demands of Elite Rugby Union Officials.
AB  - PURPOSE: To examine the movement and physiological demands of rugby union
      officiating in elite competition. METHODS: Movement demands of 9 elite officials
      across 12 Super Rugby matches were calculated, using global positioning system
      devices. Total distance (in m), relative distance (in m.min-1), and percentage
      time spent in various speed zones were calculated across a match. Heart-rate (HR)
      responses were also recorded throughout each match. Cohen d effect sizes were
      reported to examine the within-match variations. RESULTS: The total distance
      covered was 8030 (506) m, with a relative distance of 83 (5) m.min-1 and with no
      differences observed between halves. Most game time was spent at lower movement
      speeds (76% [2%]; <2.0 m.s-1), with large effects for time spent >7.0 m.s-1
      between halves (d = 2.85). Mean HR was 154 (10) beats.min-1 (83.8 [2.9]%HRmax),
      with no differences observed between the first and second halves. Most game time
      was spent between 81%HRmax and 90%HRmax (40.5% [7.5%]) with no observable
      differences between halves. Distances covered above 5.1 m.s-1 were highest during
      the first 10 min of a match, while distance at speeds 3.7 to 5 m.s-1 decreased
      during the final 10 min of play. CONCLUSIONS: These findings highlight the highly
      demanding and intermittent nature of rugby union officiating, with only some
      minor variations in physical and physiological demands across a match. These
      results have implications for the physical preparation of professional rugby
      union referees.

PMID- 29651858
TI  - Sleep-related Issues for Recovery and Performance in Athletes.
AB  - The body of research that reports the relevance of sleep in high-performance
      sports is growing steadily. While the identification of sleep cycles and
      diagnosis of sleep disorders is limited to lab-based assessment via
      polysomnography, the development of activity-based devices estimating sleep
      patterns provides greater insight into the sleep behaviour of athletes in
      ecological settings. Overall, small sleep quantity and/or poor quality appears to
      exist in many athletic populations, though this may be related to training and
      competition context. Typical sleep-affecting factors are the scheduling of
      training sessions and competitions as well as impaired sleep-onset as a result of
      increased arousal prior to competition or due to the use of electronic devices
      before bedtime. Further challenges are travel demands which may be accompanied by
      jet-lag symptoms and disruption of sleep habits. Promotion of sleep may be
      approached via behavioural strategies, such as sleep hygiene, extending night
      time sleep or daytime napping. Pharmacological interventions should be limited to
      clinically-induced treatments as evidence among healthy and athletic populations
      is lacking. To optimise and manage sleep in athletes, it is recommended to
      implement routine sleep monitoring on an individual basis.

PMID- 29651859
TI  - Effect of amino acid substitution in New Delhi metallo-beta-lactamase on
      carbapenem susceptibility.
AB  - The aim of this work was investigation of clinically important amino acid
      substitutions of NDM-1 variants. A blaNDM-1 gene was cloned into expression
      vector pET100/D-TOPO. The sequence of NDM-1 variants with substituted amino acids
      was determined by ClustalW program. A pET100/D-TOPO + blaNDM-1 was used to
      generate the alanine mutations at different positions, such as NDM-2 (P28A), NDM
      3 (D95A), NDM-4 (M154A), NDM-5 (V88A), NDM-7 (D130A), and NDM-9 (E152A). The
      mutant variants were transformed into Escherichia coli DH5alpha. Changes in the
      activities of alanine mutation variants were determined by E-test. All samples
      had 32 MUg/ml MIC values against ampicillin. The 28th amino acid mutation sample
      had the highest MIC value against ceftazidime, whereas decreased MIC value for
      piperacillin. It was observed that the resistance to imipenem was increased in
      mutant variants D95A, M154A, D130A, and E152A, comparing with P28A and V88A. It
      was found that NDM-1 has 0.64 MUg/ml and the 130th amino acid mutation sample has
      0.75 MUg/ml meropenem MIC value.

PMID- 29651860
TI  - Risk factors for Clostridium difficile infections in Baranya County, Southern
      Hungary.
AB  - In the past decade, Clostridium difficile infections (CDIs) have become a major
      public health challenge. Their epidemiology has radically changed with a
      significant rise in the number of cases and an increase in severe episodes.
      Recurrence and failure of conventional treatments are very common. Furthermore, a
      spread of CDI has emerged in general population without the usual risk factors
      (unexposed to antibiotic treatment, young people, etc.). The conventional
      treatments (metronidazole and vancomycin) are still effective and are the first
      line antibiotics with new recommendations. New therapeutic strategies are now
      available. Recent studies show a better efficacy of vancomycin compared with
      metronidazole for severe episodes. Fidaxomicin is a novel antibiotic drug with an
      efficacy similar to vancomycin and a lower risk of recurrence. Finally, for
      relapsing forms, fecal microbiota transplantation (FMT) seems to be the best
      option. We determined risk factors for CDI among patients treated at the
      infectious diseases ward of our hospital in Pecs. The study included 886 patients
      with CDI from 2009 to 2014. The average number of recurrent episodes was 2.16 and
      the proportion of severe cases was 66%. Among our patients, 726 (82%) had taken
      antibiotics and 769 (86.8%) had been hospitalized in the prior 3 months before
      developing CDI. We have found that prior statin use could be a significant risk
      factor of CDI (OR: 1.7765, 95% CI: 1.3966-2.2597, p < 0.0001). Finally, we
      present the comparative efficacy of different types of treatment (metronidazole,
      vancomycin, fidaxomicin, and FMT).

PMID- 29651861
TI  - The first characterized carbapenem-resistant Bacteroides fragilis strain from
      Croatia and the case study for it.
AB  - An imipenem-resistant Bacteroides fragilis strain was isolated from the blood of
      a 72-year-old male patient with a urinary bladder tumor in Osijek, Croatia. This
      strain was also resistant to ampicillin, piperacillin/tazobactam, cefoxitin,
      clindamycin, tetracycline, and harbored cfiA, ermF, and tetQ genes where the high
      level expression of the cfiA carbapenem-resistant gene was driven by an IS1187
      element. Interestingly, despite the carbapenem-resistant feature of the B.
      fragilis from blood, the patient relatively easily recovered from the bacteremia.
      It was the first characterized imipenem-resistant B. fragilis isolate with its
      case report from Croatia, which confirmed the appearance of carbapenem-resistant
      B. fragilis strains, that continues worldwide with low incidence and the
      molecular characteristics vary temporally and geographically.

PMID- 29651862
TI  - beta-Alanine Supplementation's Improvement of High-Intensity Game Activities in
      Water Polo.
AB  - OBJECTIVES: To investigate whether 4 wk of beta-alanine supplementation improves
      total distance covered, distance covered and time spent in different speed zones,
      and sprint numbers during a simulated water polo game. DESIGN: Double-blind,
      parallel, and placebo controlled. A total of 11 male water polo players
      participated in the study, divided randomly into 2 homogeneous groups (placebo
      and beta-alanine). METHODS: The participants performed a simulated water polo
      game before and after the supplementation period (4 wk). They received 4.8 g.d-1
      of dextrose or beta-alanine on the first 10 d and 6.4 g.d-1 on the final 18 d.
      RESULTS: Only the beta-alanine group presented a significant improvement in total
      sprint numbers compared with the presupplementation moment (PRE = 7.8 [5.2]
      arbitrary units [a.u.]; POST = 20.2 [7.8] a.u.; P = .002). Furthermore, beta
      alanine supplementation presented a likely beneficial effect in improving total
      distance covered (83%) and total time spent (81%) in speed zone 4 (ie, speed >=
      1.8 m.s-1). There was no significant interaction effect (group * time) for any
      variable. CONCLUSIONS: Four weeks of beta-alanine supplementation slightly
      improved sprint numbers and had a likely beneficial effect on improving distance
      covered and time spent in speed zone 4 in a simulated water polo game.

PMID- 29651863
TI  - Incarnation and the dynamics of medical promises: DHEA as a fountain of youth
      hormone.
AB  - For more than a decade, the sociology of hope and expectations has gained growing
      influence in the social studies of health, medicine, and healthcare. This
      literature has stressed the role of representations of the future-through images,
      metaphors, theories, or visions-in the medical sector and analyzed the
      translation of these discursive contents into social practices and organizations.
      This article builds on these results and intends to explore a dimension that has
      received less attention: the incarnation of medical promises. Looking at the
      evolving case of a particular molecule, dehydroepiandrosterone (DHEA)-which has
      been promoted from the mid-1990s onwards as a "fountain of youth" pill-, we
      emphasize that testimonies by and portrayals of those who are undergoing a
      treatment with uncertain risks and benefits, and representations of their bodies
      in the media, can play a key role in the performativity of a medical promise. We
      analyze this incarnation as a specific "form of veridiction" and stress its
      normative dimension. This leads us to underline how evidence-based medicine and
      experiential knowledge-which are often analyzed as two opposite sources of
      information-can intricate and give rise to the same incarnation dynamics.

PMID- 29651864
TI  - Exogenous skeletal muscle satellite cells promote the repair of levator palpebrae
      superioris mechanical damage in rat.
AB  - AIM OF THE STUDY: Blepharoptosis is a drooping of the upper eyelid, usually due
      to dysfunction of the levator palpebrae superioris (LPS). Recently, skeletal
      muscle satellite cells (SSCs) have been reported to promote the repair of damaged
      skeletal muscle. This study aims to investigate the potential contribution of
      exogenous SSCs to the regeneration of mechanically damaged LPS. MATERIALS AND
      METHODS: Thirty-two rats were randomly divided into four groups, including
      control group, SSCs-treated group, SSCs-treated injury group and non-treated
      injury group. After rats in injury groups were artificially lacerated on both the
      left and right LPS, HBBS (Hank's Balanced Salt Solution) containing SSCs was
      injected into upper eyelid tissue. After 7 days, the LPS muscle tissues were
      excised. In addition, skeletal muscle cells (SMCs) and SSCs were cocultured for
      use as an in vitro model, and the protective effects of SSCs on cultured SMCs
      were also investigated. RESULTS: Histological staining revealed that exogenous
      SSCs repaired the damaged muscle fibers and attenuated the fibrosis of LPS,
      possibly due to the increased level of IGF-1. In contrast, the level of IL-1beta,
      IL-6, TGF-beta1 and Smad2/3 (phospho-T8) were significantly reduced in the SSCs
      treated group. The in vitro model using coculture of skeletal muscle cells (SMCs)
      and SSCs also revealed an increased level of IGF-1 and reduced level of
      inflammatory factors, resulting in a better cell survival rate. CONCLUSIONS: This
      study found that exogenous SSCs can promote the repair of LPS mechanical damage
      and provides new insight into the development of novel therapeutic approaches for
      blepharoptosis.

PMID- 29651865
TI  - Compound Heterozygosity for Hb Alperton (HBB: c.407C>T) and IVS-I-5 (G>C) (HBB:
      c.92+5G>C) Mutations Presenting as a Moderate Anemia in an Indian Family.
AB  - While knowledge of HBB gene mutations is necessary for offering prenatal
      diagnosis (PND) of beta-thalassemia (beta-thal), a genotype-phenotype correlation
      may not always be available for rare variants. We present for the first time,
      genotype-phenotype correlation for a compound heterozygous status with IVS-I-5
      (G>C) (HBB: c.92+5G>C) and HBB: c.407C>T (Hb Alperton) mutations on the HBB gene
      in an Indian family. Hb Alperton is a very rare hemoglobin (Hb) variant with
      scant published information about its clinical presentation, especially when
      accompanied with another HBB gene mutation. Here we provide biochemical as well
      as clinical details of this variant.

PMID- 29651866
TI  - Emotional distress after myocardial infarction: Importance of cardiorespiratory
      fitness.

PMID- 29651868
TI  - The mandate and work of ICRP Committee 2 on doses from radiation exposure.
AB  - The practical implementation of the International Commission on Radiological
      Protection's (ICRP) system of radiological protection requires the availability
      of appropriate methodology and data. Over many years, ICRP Committee 2 has
      provided sets of dose coefficients to allow users to evaluate equivalent and
      effective doses for radiation exposures of workers and members of the public. The
      methodology being applied in the calculation of doses is state-of-the-art in
      terms of the biokinetic models used to describe the behaviour of inhaled and
      ingested radionuclides, and the dosimetric models used to model radiation
      transport for external and internal exposures. This overview provides an outline
      of recent work and future plans, including publications on dose coefficients for
      adults, children, and in-utero exposures, with new dosimetric phantoms in each
      case. For the first time, ICRP will publish dose coefficients for intakes of
      radon isotopes calculated using dosimetric models. Committee 2 is also working
      with Committee 3 on dose coefficients for radiopharmaceuticals, and leading a
      cross-committee initiative to provide advice on the use of effective dose. The
      remit of Committee 2 has now been widened to include all data requirements for
      the assessment of doses to humans and non-human biota.

PMID- 29651867
TI  - Molecular modelling insights into a physiologically favourable approach to
      eicosanoid biosynthesis inhibition through novel thieno[2,3-b]pyridine
      derivatives.
AB  - In this research, we exploited derivatives of thieno[2,3-b]pyridine as dual
      inhibitors of the key enzymes in eicosanoid biosynthesis, cyclooxygenase (COX,
      subtypes 1 and 2) and 5-lipoxygensase (5-LOX). Testing these compounds in a rat
      paw oedema model revealed potency higher than ibuprofen. The most active
      compounds 7a, 7b, 8b, and 8c were screened against COX-1/2 and 5-LOX enzymes.
      Compound 7a was the most powerful inhibitor of 5-LOX with IC50 = 0.15 uM, while
      its p-chloro analogue 7b was more active against COX-2 (IC50 = 7.5 uM). The less
      desirable target COX-1 was inhibited more potently by 8c with IC50 = 7.7 uM.
      Surflex docking programme predicted that the more stable anti- conformer of
      compound (7a) formed a favourable complex with the active site of 5-LOX but not
      COX-1. This is in contrast to the binding mode of 8c, which resembles the syn
      conformer of series 7 and binds favourably to COX-1.

PMID- 29651869
TI  - New mesh-type phantoms and their dosimetric applications, including emergencies.
AB  - Committee 2 of the International Commission on Radiological Protection (ICRP) has
      constructed mesh-type adult reference computational phantoms by converting the
      voxel-type ICRP Publication 110 adult reference computational phantoms to a high
      quality mesh format, and adding those tissues that were below the image
      resolution of the voxel phantoms and therefore not included in the Publication
      110 phantoms. The new mesh phantoms include all the necessary source and target
      tissues for effective dose calculations, including the 8-40-um-thick target
      layers of the alimentary and respiratory tract organs, thereby obviating the need
      for supplemental organ-specific stylised models (e.g. respiratory airways,
      alimentary tract organ walls and stem cell layers, lens of the eye, and skin
      basal layer). To see the impact of the new mesh-type reference phantoms, dose
      coefficients for some selected external and internal exposures were calculated
      and compared with the current reference values in ICRP Publications 116 and 133,
      which were calculated by employing the Publication 110 phantoms and the
      supplemental stylised models. The new mesh phantoms were also used to calculate
      dose coefficients for industrial radiography sources near the body, which can be
      used to estimate the organ doses of the worker who is accidentally exposed by an
      industrial radiography source; in these calculations, the mesh phantoms were
      deformed to reflect the size of the worker, and also to evaluate the effect of
      posture on dose coefficients.

PMID- 29651870
TI  - Utilization of Complementary and Alternative Medicine in Multiethnic Population:
      The Malaysian Cohort Study.
AB  - BACKGROUND: This study aimed to identify the factors of CAM usage for general
      health and to determine the factors associated with the usage of different types
      of CAM after the diagnosis of chronic diseases among The Malaysian Cohort
      participants. METHODS: This was a cross-sectional study derived from The
      Malaysian Cohort (TMC) project, a prospective population-based cohort aged
      between 35 to 65 years old that recruited from April 2006 to September 2012.
      Association between the CAM usage and contributing factors were determined via
      logistic regression. RESULTS: The sample were mostly female (58.1%), Malays
      (43.1%), came from urban (71.9%), aged 44 years and below (26.8%) and had
      secondary education (45.9%). The prevalence of CAM usage varied across diseases;
      62.8% in cancer patients, 53.3% in hypercholesterolemia, 49.4% in hypertensives
      and 48.6% in diabetics. General CAM usage was greater among female (OR: 1.54, 95%
      CI: 1.49, 1.59), Chinese (OR: 1.15, 95% CI: 1.12, 1.19), those with higher
      education (OR: 3.12, 95% CI: 3.00, 3.25), urban residents (OR: 1.55, 95% CI:
      1.50, 1.61) and older people (OR ranging from 1.15 to 1.75) while for post
      diagnosis of chronic diseases usage, the odds were higher among those with lower
      education and living in rural areas. CONCLUSION: Health status, educational
      level, age, living location and types of chronic diseases were significant
      factors that influence CAM usage for the intent of either health maintenance or
      disease treatment. Further exploration on CAM safety and benefit are crucial to
      minimize the adverse effect and to ensure the efficacy of CAM product.

PMID- 29651871
TI  - Outcome of the European initiative for radiation protection research and future
      perspectives.
AB  - In 2009, the European Commission published the report of the high-level expert
      group that had been mandated to consider the scientific challenges posed by the
      issues of low dose effects of ionising radiation, and to formulate proposals for
      research policy evolution in this field at European level. This report formulated
      a first draft of a strategic research agenda. International scientific
      cooperation and an integrated approach are essential for the further development
      and enhancement of the international framework of radiation protection. This
      paper reflects on the results which have been gained through this integration
      approach: strategic research agendas have been established, policies and action
      plans have been developed for infrastructures and training education, several
      ambitious research projects have been launched, and a first draft of a European
      'joint road map' for radiation protection research will be published. Reflecting
      on the challenges that lie ahead, this paper also presents the initiatives that
      the five European research platforms (MELODI: low dose research; ALLIANCE:
      radioecology; EURADOS: dosimetry; NERIS: emergency preparedness; EURAMED:
      radiation protection in medical applications) have jointly presented to the
      European Commission and Euratom member states to further enhance radiation
      protection research.

PMID- 29651872
TI  - The effectiveness of 12 weeks of Pilates intervention on disability, pain and
      kinesiophobia in patients with chronic low back pain: a randomized controlled
      trial.
AB  - OBJECTIVE: To assess the effectiveness of 12 weeks of Pilates practice on
      disability, pain and kinesiophobia in patients with chronic non-specific low back
      pain. DESIGN: This is a randomized controlled trial. SETTING: This study was
      conducted in the university laboratory. SUBJECTS: A total of 64 participants with
      chronic non-specific low back pain were included. INTERVENTIONS: Participants
      were randomly allocated to intervention group consisted in Pilates intervention
      during 12 weeks ( n = 32) or control group who received no treatment ( n = 32).
      MAIN MEASURES: Disability, pain and kinesiophobia were assessed by Roland Morris
      Disability Questionnaire, visual analogue scale and Tampa Scale of Kinesiophobia,
      respectively. Measurements were performed at baseline, at 6 and 12 weeks after
      study completion. RESULTS: There were significant differences between groups with
      observed improvement in Pilates intervention group in all variables after
      treatment ( P < 0.001). Major changes on disability and kinesiophobia were
      observed at six weeks of intervention with no significant difference after 12
      weeks ( P < 0.001). Mean changes of the intervention group compared with the
      control group were 4.00 (0.45) on the Roland Morris Disability Questionnaire and
      5.50 (0.67) in the Tampa Scale of Kinesiophobia. Pain showed better results at
      six weeks with a slightly but statistically significant improvement at 12 weeks
      with Visual Analogue Scale scores of 2.40 (0.26) ( P < 0.001). CONCLUSION:
      Pilates intervention in patients with chronic non-specific low back pain is
      effective in the management of disability, pain and kinesiophobia.

PMID- 29651873
TI  - Effectiveness of virtual reality training for balance and gait rehabilitation in
      people with multiple sclerosis: a systematic review and meta-analysis.
AB  - OBJECTIVE: To evaluate the evidence for the use of virtual reality to treat
      balance and gait impairments in multiple sclerosis rehabilitation. DESIGN:
      Systematic review and meta-analysis of randomized controlled trials and quasi
      randomized clinical trials. METHODS: An electronic search was conducted using the
      following databases: MEDLINE (PubMed), Physiotherapy Evidence Database (PEDro),
      Cochrane Database of Systematic Reviews (CDSR) and (CINHAL). A quality assessment
      was performed using the PEDro scale. The data were pooled and a meta-analysis was
      completed. This systematic review was conducted in accordance with the (Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses) PRISMA guideline
      statement. It was registered in the PROSPERO database (CRD42016049360). RESULTS:
      A total of 11 studies were included. The data were pooled, allowing meta-analysis
      of seven outcomes of interest. A total of 466 participants clinically diagnosed
      with multiple sclerosis were analysed. Results showed that virtual reality
      balance training is more effective than no intervention for postural control
      improvement (standard mean difference (SMD) = -0.64; 95% confidence interval (CI)
      = -1.05, -0.24; P = 0.002). However, significant overall effect was not showed
      when compared with conventional training (SMD = -0.04; 95% CI = -0.70, 0.62; P =
      0.90). Inconclusive results were also observed for gait rehabilitation.
      CONCLUSION: Virtual reality training could be considered at least as effective as
      conventional training and more effective than no intervention to treat balance
      and gait impairments in multiple sclerosis rehabilitation.

PMID- 29651874
TI  - In vitro and in vivo evaluation of osteoinductivity and bone fusion ability of an
      activin a/BMP2 chimera (AB204): a comparison study between AB204 and rhBMP-2.
AB  - This study compared osteoinductivity and osteogenic capacity between AB204 and
      rhBMP-2 using hMSCs in vitro and a beagle's posterolateral spinal fusion model.
      Cultured hMSCs were treated with AB204 or rhBMP-2 with low to high doses. Three
      male beagles were performed posterolateral spinal fusion with biphasic calcium
      phosphate (2 ml) + AB204 or rhBMP-2 (20, 50 or 200 ug). They were euthanized
      after 8 weeks. The fusion rate and bone formation of spine samples were examined.
      AB204 had higher alkaline phosphatase activity, mineralization and osteogenic
      related gene expression than rhBMP-2. Fusion rates in all rhBMP-2 groups were 0.
      They were 100% for 50 MUg and 200 MUg AB204 groups. Therefore, AB204 showed
      higher osteogenicity than rhBMP-2. It could be a better bone graft substitute.

PMID- 29651875
TI  - Is severe emphysema, as defined by quantitative CT measurement, a negative risk
      factor of radiation fibrosis?
AB  - OBJECTIVE: To investigate whether patients with emphysema, as evaluated by
      quantitative CT image measurement, are at risk of developing radiation
      pneumonitis (RP) after radiotherapy (RT) for non-small cell lung cancer (NSCLC).
      METHODS: Between March 2011 and June 2015, 68 consecutive patients with Stage I
      NSCLC treated with a RT dose of 75 Gy given in 30 fractions were enrolled. The
      median age was 79 years and there were 45 males and 23 females. The number of
      patients with T1 and T2 were 49 and 19, respectively. The severity of emphysema
      was evaluated by the percentages of the low attenuation area (LAA) of <=-860 or 
      950 Hounsfield unit (HU) and average HU in the whole lung. RESULTS: The mean
      difference percentages of LAA of <=-860 (p = 0.0004) or -950 HU (p = 0.005) and
      average HU (p = 0.001) in patients with RP were significantly lower than those in
      patients without RP. The area under curve (AUC) of average HU was significantly
      higher than AUC of LAA of <=-860 (p < 0.0001) or -950 HU (p < 0.0001). The RP
      rate after RT was significantly lower when the average HU values were <=-850 HU
      (p = 0.0003). CONCLUSION: Patients with emphysema evaluated by average HU (<=-850
      HU) in the whole lung were found to be at low risk of RP after RT. Advances in
      Knowledge: Quantitative measurement of average HU from CT images was predicted of
      RP after RT.

PMID- 29651877
TI  - First, to understand the present situation!: Transcutaneous aortic valve
      implantation as a real global treatment for severe aortic stenosis.

PMID- 29651876
TI  - Novel hits for acetylcholinesterase inhibition derived by docking-based screening
      on ZINC database.
AB  - The inhibition of the enzyme acetylcholinesterase (AChE) increases the levels of
      the neurotransmitter acetylcholine and symptomatically improves the affected
      cognitive function. In the present study, we searched for novel AChE inhibitors
      by docking-based virtual screening of the standard lead-like set of ZINC database
      containing more than 6 million small molecules using GOLD software. The top 10
      best-scored hits were tested in vitro for AChE affinity, neurotoxicity, GIT and
      BBB permeability. The main pharmacokinetic parameters like volume of
      distribution, free fraction in plasma, total clearance, and half-life were
      predicted by previously derived models. Nine of the compounds bind to the enzyme
      with affinities from 0.517 to 0.735 uM, eight of them are non-toxic. All hits
      permeate GIT and BBB and bind extensively to plasma proteins. Most of them are
      low-clearance compounds. In total, seven of the 10 hits are promising for further
      lead optimisation. These are structures with ZINC IDs: 00220177, 44455618,
      66142300, 71804814, 72065926, 96007907, and 97159977.

PMID- 29651878
TI  - In Vivo Hypoglycemic Effect of Kigelia africana (Lam): Studies With Alloxan
      Induced Diabetic Mice.
AB  - The claims by the traditional herbal medicine practitioners that Kigelia africana
      has bioactivity against several diseases, including diabetes mellitus, were
      investigated in this study. Type I diabetes mellitus was induced in mice by
      intraperitoneal administration of alloxan monohydrate followed by treatment with
      the therapeutic doses of the aqueous and ethyl acetate leaf extract of K africana
      to the experimentally diabetic mice. The treatment effects were compared with the
      normal control, diabetic control, and diabetic control rats treated with a
      standard antidiabetic drugs (insulin administered intraperitoneally at 1 IU/kg
      body weight in 0.1 mL physiological saline or glibenclamide administered orally
      at 3 mg/kg body weight in 0.1 mL physiological saline). Phytochemical composition
      of the leaf extract was assessed using standard procedures and mineral elements
      assessed using atomic absorption spectrophotometry and total reflection X-ray
      fluorescence system. Oral and intraperitoneal administration of the aqueous and
      ethyl acetate leaf extract caused a statistically significant dose-independent
      reduction in plasma glucose level in alloxan-induced diabetic mice. The observed
      hypoglycemic activity of this plant extract could be attributed to the observed
      phytochemicals and trace elements, which have been associated with exhibiting
      antidiabetic properties. Therefore, the data appear to support the hypoglycemic
      effects of K africana validating its folkloric usage.

PMID- 29651879
TI  - Src kinase activation by nitric oxide promotes resistance to anoikis in tumour
      cell lines.
AB  - Tumour progression involves the establishment of tumour metastases at distant
      sites. Resistance to anoikis, a form of cell death that occurs when cells lose
      contact with the extracellular matrix and with neighbouring cells, is essential
      for metastases. NO has been associated with anoikis. NO treated HeLa cells and
      murine melanoma cells in suspension triggered a nitric oxide (NO)-Src kinase
      signalling circuitry that enabled resistance to anoikis. Two NO donors, sodium
      nitroprusside (SNP) (500 uM) and DETANO (125 uM), protected against cell death
      derived from detachment of a growth permissive surface (experimental anoikis).
      Under conditions of NO-mediated Src activation the following were observed: (a)
      down-regulation of the pro-apoptotic proteins Bim and cleaved caspase-3 and the
      cell surface protein, E-cadherin, (b) up-regulation of caveolin-1, and (c) the
      dissociation of cell aggregates formed when cells are detached from a growth
      permissive surface. Efficiency of reattachment of tumour cells in suspension and
      treated with different concentrations of an NO donor, was dependent on the NO
      concentration. These findings indicate that NO-activated Src kinase triggers a
      signalling circuitry that provides resistance to anoikis, and allows for
      metastases.

PMID- 29651881
TI  - Oxidative stress in epilepsy.
AB  - INTRODUCTION: The brain is particularly susceptible to oxidative stress being the
      most aerobically active organ in the body due to its high metabolic demands.
      There is evidence that neuronal hyperexcitability and oxidative injury produced
      by an excessive production of free radicals may play a role in the initiation and
      progression of epilepsy. Understanding the role of oxidative stress in
      epileptogenesis is essential to delineate appropriate therapeutic strategies.
      Neuroprotectant or antioxidant compounds may exert positive effects when
      associated with antiepileptic drugs (AEDs). Areas covered: This review aims to
      outline the current state of knowledge on the relationship between oxidative
      stress and epilepsy. The role of neuroprotectants in the therapeutic strategy to
      prevent or treating epilepsy is also discussed. PubMed/Medline database was
      searched for relevant articles on the relation between oxidative stress and
      epilepsy and on antioxidant strategies for epilepsy management. Expert
      commentary: Therapeutic intervention with antioxidants may represent a key
      strategy to counteract the epilepsy-related neurodegenerative process. However,
      in spite of the incredible development of new drugs for epilepsy treatment,
      definitive evidence about the neuroprotective ability of the existing compounds
      is still lacking. Therefore, there is great need for clinical trials to evaluate
      new antioxidant compounds specifically on epileptic patients.

PMID- 29651882
TI  - Ambient air pollution as a new risk factor for cardiovascular diseases: Time to
      take action.

PMID- 29651883
TI  - LncRNA DANCR Promotes Lung Cancer by Sequestering miR-216a.
AB  - BACKGROUND: Long noncoding RNAs (lncRNAs) are a new class of cancer regulators.
      Here, we aimed to investigate the diagnostic and therapeutic values of an lncRNA,
      differentiation antagonizing noncoding RNA (DANCR), in lung cancer. METHODS: Real
      time polymerase chain reaction was used to compare DANCR levels in normal and
      cancerous lung tissues as well as lung cancer cells. Lentiviral transduction was
      used to induce DANCR overexpression or silencing in vitro, followed by monitoring
      cell proliferation, colony formation, and changes in microRNA-216a (miR-216a)
      expression. DANCR-specific small hairpin RNA transduction was used to establish
      cells with stable DANCR knockdown, and silenced cells were used to initiate lung
      tumor xenografts, followed by monitoring tumor growth. RESULTS: DANCR
      upregulation was seen in lung cancer, particularly in high-grade lung cancer
      tissues and aggressive cancer cells. Ectopic DANCR expression induced lung cancer
      cell proliferation and colony formation, whereas DANCR silencing induced opposing
      effects. The miR-216a level in cancer cells was negatively correlated with DANCR
      expression. The DANCR knockdown reduced the growth of tumor xenografts in vivo.
      CONCLUSION: DANCR upregulation is a potential indicator of aggressive lung
      cancer. Silencing of DANCR has great potential as a potent therapeutic strategy
      in lung cancer.

PMID- 29651880
TI  - Small molecule KDM4s inhibitors as anti-cancer agents.
AB  - Histone demethylation is a vital process in epigenetic regulation of gene
      expression. A number of histone demethylases are present to control the
      methylated states of histone. Among these enzymes, KDM4s are one subfamily of
      JmjC KDMs and play important roles in both normal and cancer cells. The discovery
      of KDM4s inhibitors is a potential therapeutic strategy against different
      diseases including cancer. Here, we summarize the development of KDM4s inhibitors
      and some related pharmaceutical information to provide an update of recent
      progress in KDM4s inhibitors.

PMID- 29651887
TI  - Validity and Reliability of the 3-Minute All-Out Test in National and
      International Competitive Swimmers.
AB  - PURPOSE: To assess the concurrent and predictive validity of the 3-minute all-out
      test (3MT) against conventional methods (CM) of determining critical speed (CS)
      and curvature constant (D') and to examine the test-retest reliability of the 3MT
      in highly trained swimmers. METHODS: Thirteen highly trained swimmers (age 16 [2]
      y, weight 64.7 [8.5] kg, height 1.76 [0.07] m) completed 4 time trials and two
      3MTs over 2 wk. The distance-time (DT) and speed-1/time (1/T) models were used to
      determine CS and D' from 4 time trials. CS3MT and [Formula: see text] were
      determined as the mean speed in the final 30 s of 3MT and as the speed-time
      integral above CS, respectively. RESULTS: CS3MT (1.33 [0.06] m.s-1) did not
      differ from CSCM (1.33 [0.06] m.s-1, P > .05) and correlated nearly perfectly
      with CSCM (r = .95, P < .0001). [Formula: see text] (19.50 [3.52] m) was lower
      than [Formula: see text] (23.30 [6.24] m, P < .05) and [Formula: see text] (22.15
      [5.75] m, P = .09). Correlations between [Formula: see text] and [Formula: see
      text] were very large (r = .79, P = .002). CS and D' between the two 3MT trials
      were not different (CS mean change = -0.009 m.s-1, P = .102; D' mean change =
      0.82 m, P = .221). Correlations between the two 3MT trials were nearly perfect
      and very large for CS (r = .97) and D' (r = .87, P < .05), respectively, with
      coefficients of variation of 0.9% for CS and 9.1% for D'. CONCLUSION: The 3MT is
      a valid protocol for estimation of CS and produces high test-retest reliability
      for CS and D' in highly trained swimmers.

PMID- 29651888
TI  - Mechanisms of Performance Improvements Due to a Leading Teammate During Uphill
      Cycling.
AB  - PURPOSE: To identify the impact of a leading teammate in front of a cyclist on
      psychological, physiological, biomechanical, and performance parameters during an
      uphill maximal effort. METHODS: After familiarization, 12 well-trained
      competitive cyclists completed 2 uphill time trials (UTTs, 2.7 km at 7.4%) in
      randomized order; that is, 1 performed alone (control condition) and 1 followed a
      simulated teammate during the entire UTT (leader condition). Performance (UTT
      time) and mean power output (PO) were recorded for each UTT. For physiological
      parameters, mean heart rate and postexercise blood lactate concentration were
      recorded. Psychological parameters (rating of perceived exertion, pleasure, and
      attentional focus) were collected at the end of each trial. RESULTS: Performance
      (UTT time) significantly improved by 4.2% (3.1%) in the leader condition, mainly
      due to drafting decrease of the aerodynamic drag (58% of total performance gains)
      and higher end spurt (+9.1% [9.1%] of mean PO in the last 10% of the UTT).
      However, heart rate and postexercise blood lactate concentration were not
      significantly different between conditions. From a psychological aspect, higher
      pleasure was observed in the leader condition (+41.1% [51.7%]), but attentional
      focus was not significantly different. CONCLUSIONS: The presence of a leading
      teammate during uphill cycling had a strong impact on performance, enabling
      higher speed for the same mean PO and greater end spurt. These results explain
      why the best teams competing for the general classification of the most
      prestigious and contested races like the Grand Tours tend to always protect their
      leader with teammates during decisive ascents.

PMID- 29651884
TI  - Kinetic and structural studies on the interactions of Torpedo californica
      acetylcholinesterase with two donepezil-like rigid analogues.
AB  - Acetylcholinesterase inhibitors were introduced for the symptomatic treatment of
      Alzheimer's disease (AD). Among the currently approved inhibitors, donepezil
      (DNP) is one of the most preferred choices in AD therapy. The X-ray crystal
      structures of Torpedo californica AChE in complex with two novel rigid DNP-like
      analogs, compounds 1 and 2, have been determined. Kinetic studies indicated that
      compounds 1 and 2 show a mixed-type inhibition against TcAChE, with Ki values of
      11.12 +/- 2.88 and 29.86 +/- 1.12 nM, respectively. The DNP rigidification
      results in a likely entropy-enthalpy compensation with solvation effects
      contributing primarily to AChE binding affinity. Molecular docking evidenced the
      molecular basis for the binding of compounds 1 and 2 to the active site of beta
      secretase-1. Overall, these simplified DNP derivatives may represent new
      structural templates for the design of lead compounds for a more effective
      therapeutic strategy against AD by foreseeing a dual AChE and BACE-1 inhibitory
      activity.

PMID- 29651889
TI  - How to conduct research of rare autoimmune diseases.
AB  - Rare autoimmune diseases are difficult to conduct researches in spite of present
      era with advanced scientific progress. Research using genetic approach is a
      promising way since genetic findings implicate causality of diseases. Still,
      there are multiple obstacles preventing genetic studies of rare diseases. Here,
      we list up the problems and propose solutions for them with detailed examples.
      The biggest problem is that it is difficult to collect a substantial number of
      DNA samples from patients with rare diseases. We propose to collaborate not only
      with academic institutions and hospitals but with patients' groups. Detailed
      examples include studies about Takayasu arteritis (TAK), relapsing
      polychondritis, and systemic sclerosis. In TAK, we identified IL12B, a key gene
      which seems to play a central role in the disease. After getting evidence of
      IL12p40 encoded by IL12B as a possible therapeutic target by showing similarities
      of the genetic background between TAK and ulcerative colitis, we performed a
      pilot clinical study of ustekinumab, a monoclonal antibody against IL12p40 for
      patients with refractory TAK and obtained good response. This is a good example
      of how genetic findings in a rare disease lead to development of new therapeutic
      option.

PMID- 29651891
TI  - Use of Vagus Nerve Stimulator on Children With Primary Generalized Epilepsy.
AB  - OBJECTIVE: To describe the response to vagus nerve stimulator (VNS) in otherwise
      neurotypical children with medically intractable primary generalized epilepsy.
      METHODS: Retrospective chart review of patients who underwent vagus nerve
      stimulator surgery between January 2011 and December 2015. RESULTS: Eleven
      patients were identified. Median follow-up duration was 2.5 years (1.2-8.4
      years). Prior to vagus nerve stimulator surgery, all patients had at least 1
      seizure per week, and 7/11 (64%) had daily seizures. At 1-year follow-up after
      vagus nerve stimulator, 7/11 (64%) reported improved seizure frequency and 6/11
      (55%) reported fewer than 1 seizure per month. Three patients (27%) reported
      complications related to vagus nerve stimulator surgery, and no patients required
      device removal. SIGNIFICANCE: In children with medically intractable primary
      generalized epilepsy, vagus nerve stimulator is well tolerated and appears to
      lead to improvement in seizure frequency. Improvement was not attributable to
      epilepsy classification, age at vagus nerve stimulator implantation, output
      current, duty cycle, or follow-up duration.

PMID- 29651890
TI  - Can Postural Control Asymmetry Predict Falls in People With Parkinson's Disease?
AB  - This study aimed to determine the relationship between postural asymmetry and
      falls in Parkinson's disease (PD). In total, 28 patients with PD were included.
      Postural control was analyzed in bipedal, tandem, and unipedal standing. Center
      of pressure (CoP) parameters were calculated for both limbs, and asymmetry was
      assessed using the asymmetry index. Logistic regression was used to
      predict/classify fallers through postural asymmetry. The Spearman correlation was
      performed to relate asymmetry and falls number. Poisson regression models were
      created to predict the number of falls in each condition. The results
      demonstrated that asymmetry can classify 75% of fallers and nonfallers. Asymmetry
      in anteroposterior-mean velocity of CoP in unipedal standing was related to the
      number of falls. Poisson regression showed that anteroposterior-mean velocity of
      CoP predicts falls in PD, indicating that increased asymmetry results in a
      greater number of falls. Anteroposterior-mean velocity of CoP seems to be a
      sensitive parameter to detect falls in PD, mainly during a postural challenging
      task.

PMID- 29651892
TI  - The intracerebral hemorrhage blood transcriptome in humans differs from the
      ischemic stroke and vascular risk factor control blood transcriptomes.
AB  - Understanding how the blood transcriptome of human intracerebral hemorrhage (ICH)
      differs from ischemic stroke (IS) and matched controls (CTRL) will improve
      understanding of immune and coagulation pathways in both disorders. This study
      examined RNA from 99 human whole-blood samples using GeneChip(r) HTA 2.0 arrays
      to assess differentially expressed transcripts of alternatively spliced genes
      between ICH, IS and CTRL. We used a mixed regression model with FDR-corrected
      p(Dx) < 0.2 and p < 0.005 and |FC| > 1.2 for individual comparisons. For time
      dependent analyses, subjects were divided into four time-points: 0(CTRL), <24 h,
      24-48 h, >48 h; 489 transcripts were differentially expressed between ICH and
      CTRL, and 63 between IS and CTRL. ICH had differentially expressed T-cell
      receptor and CD36 genes, and iNOS, TLR, macrophage, and T-helper pathways. IS had
      more non-coding RNA. ICH and IS both had angiogenesis, CTLA4 in T lymphocytes,
      CD28 in T helper cells, NFAT regulation of immune response, and glucocorticoid
      receptor signaling pathways. Self-organizing maps revealed 4357 transcripts
      changing expression over time in ICH, and 1136 in IS. Understanding ICH and IS
      transcriptomes will be useful for biomarker development, treatment and prevention
      strategies, and for evaluating how well animal models recapitulate human ICH and
      IS.

PMID- 29651893
TI  - Differences Among Overhand, 3-Quarter, and Sidearm Pitching Biomechanics in
      Professional Baseball Players.
AB  - The purpose of this study was to assess biomechanical differences among overhand,
      3-quarter, and sidearm arm slot professional baseball pitchers. It was
      hypothesized that kinematic and kinetic differences would be found among the 3
      groups, with sidearm pitchers demonstrating greater movement along the transverse
      plane and overhead pitchers demonstrating greater movement along the sagittal
      plane. Based upon arm slot angle at ball release, 30 overhand, 156 three-quarter,
      and 21 sidearm pitchers were tested using a 240-Hz motion analysis system, and 37
      kinematic and kinetic parameters were calculated. One-way analyses of variance
      (alpha = .01) was employed to assess differences among groups. The comparisons
      showed the sidearm group had less shoulder anterior force, whereas the overhand
      group had the least elbow flexion torque. At ball release, trunk contralateral
      tilt and shoulder abduction were greatest for the overhand group and least for
      sidearm group. Additionally, the sidearm group demonstrated the lowest peak knee
      height, most closed foot angle, greatest pelvis angular velocity, and shoulder
      external rotation. The overhand group had the greatest elbow flexion at foot
      contact and greatest trunk forward tilt at ball release. The greater elbow
      flexion torque and shoulder external rotation exhibited by sidearm pitchers may
      increase their risk of labral injury. Conversely, the lower shoulder anterior
      force in sidearm pitchers may indicate lower stress on shoulder joint capsule and
      rotator cuff.

PMID- 29651894
TI  - Roller Massage: A Descriptive Survey of Allied Health Professionals.
AB  - BACKGROUND: In sports medicine, the interprofessional care of athletes has become
      a frequent practice. This type of care often involves different interventions
      used among professionals. One common intervention prescribed is roller massage
      (RM) or self-myofascial release. The trends in the use of RM among allied health
      professionals are nonexistent. The surveillance of such responses has not been
      documented. PURPOSE: To survey and document responses in the knowledge, clinical
      application, and use of RM devices among allied health professionals in the
      United States. DESIGN: Cross-sectional descriptive survey study. METHODS: A 20
      question survey was sent to allied health professionals including physical
      therapists, athletic trainers, and fitness professionals. The survey covered
      topics such as demographics, beliefs about RM, preferred devices, exercise
      prescription, and client education. RESULTS: One thousand and forty-two
      professionals (N = 1042) completed the survey. Most respondents believed that RM
      decreases pain (82%) and increases mobility (76%). A high percentage use a foam
      roller in their practice (81%), recommend a full-size foam roller (49%), and
      believe the medium density (48%) is the most effective. A high proportion of
      respondents prescribe RM for injury treatment (69%) and for preexercise and
      postexercise (61%). They also recommend rolling daily for 30 seconds to 2 minutes
      per muscle group (33%) at a self-paced cadence (46%). A high percentage of
      respondents use patient-reported outcomes (74%), joint range of motion (49%), and
      movement-based testing (48%) to measure effects of RM. Eighty-seven percent use
      live instruction to educate clients, and 88% believe there is a gap in the
      research. CONCLUSION: The results of this survey document responses in the use of
      RM among allied health professionals. The reported responses provide insight into
      how professionals are using RM as an intervention and the potential gaps between
      the research and professional practice. Future studies are needed to further
      validate these findings.

PMID- 29651895
TI  - Structural biology of solute carrier (SLC) membrane transport proteins.
AB  - The human solute carriers (SLCs) comprise over 400 different transporters,
      organized into 65 families ( http://slc.bioparadigms.org/ ) based on their
      sequence homology and transport function. SLCs are responsible for transporting
      extraordinarily diverse solutes across biological membranes, including inorganic
      ions, amino acids, lipids, sugars, neurotransmitters and drugs. Most of these
      membrane proteins function as coupled symporters (co-transporters) utilizing
      downhill ion (H+ or Na+) gradients as the driving force for the transport of
      substrate against its concentration gradient into cells. Other members work as
      antiporters (exchangers) that typically contain a single substrate-binding site
      with an alternating access mode of transport, while a few members exhibit channel
      like properties. Dysfunction of SLCs is correlated with numerous human diseases
      and therefore they are potential therapeutic drug targets. In this review, we
      identified all of the SLC crystal structures that have been determined, most of
      which are from prokaryotic species. We further sorted all the SLC structures into
      four main groups with different protein folds and further discuss the well
      characterized MFS (major facilitator superfamily) and LeuT (leucine transporter)
      folds. This review provides a systematic analysis of the structure, molecular
      basis of substrate recognition and mechanism of action in different SLC family
      members.

PMID- 29651896
TI  - Cerebral serotonin transporter measurements with [11C]DASB: A review on
      acquisition and preprocessing across 21 PET centres.
AB  - Positron Emission Tomography (PET) imaging has become a prominent tool to capture
      the spatiotemporal distribution of neurotransmitters and receptors in the brain.
      The outcome of a PET study can, however, potentially be obscured by suboptimal
      and/or inconsistent choices made in complex processing pipelines required to
      reach a quantitative estimate of radioligand binding. Variations in subject
      selection, experimental design, data acquisition, preprocessing, and statistical
      analysis may lead to different outcomes and neurobiological interpretations. We
      here review the approaches used in 105 original research articles published by 21
      different PET centres, using the tracer [11C]DASB for quantification of cerebral
      serotonin transporter binding, as an exemplary case. We highlight and quantify
      the impact of the remarkable variety of ways in which researchers are currently
      conducting their studies, while implicitly expecting generalizable results across
      research groups. Our review provides evidence that the foundation for a given
      choice of a preprocessing pipeline seems to be an overlooked aspect in modern PET
      neuroscience. Furthermore, we believe that a thorough testing of pipeline
      performance is necessary to produce reproducible research outcomes, avoiding
      biased results and allowing for better understanding of human brain function.

PMID- 29651897
TI  - The Effect of Uphill and Downhill Slopes on Weight Transfer, Alignment, and Shot
      Outcome in Golf.
AB  - The aim of the study was to examine changes in weight transfer, alignment, and
      shot outcome during golf shots from flat, uphill, and downhill slopes. Twelve
      elite male golfers hit 30 shots with a 6-iron from a computer-assisted
      rehabilitation environment used to create 5 degrees  slopes while collecting 3
      dimensional kinematics and kinetics of the swing. A launch monitor measured
      performance outcomes. A shift in the center of pressure was found throughout the
      swing when performed on a slope, with the mean position moving approximately 9%
      closer to the lower foot. The golfers attempted to remain perpendicular to the
      slope, resulting in weight transfer toward the lower foot. The golfers adopted a
      wider stance in the sloped conditions and moved the ball toward the higher foot
      at address. Ball speed was not significantly affected by the slope, but launch
      angle and ball spin were. As the coaching literature predicted, golfers were more
      likely to hit shots to the left from an uphill slope and to the right from a
      downhill slope. No consistent compensatory adjustments in alignment at address or
      azimuth were found, with the change in final shot dispersion resulting from the
      lateral spin of the ball.

PMID- 29651899
TI  - Caffeine does not affect susceptibility to cortical spreading depolarization in
      mice.
AB  - Several factors that modulate migraine, a common primary headache disorder, also
      affect susceptibility to cortical spreading depolarization (CSD). CSD is a wave
      of neuronal and glial depolarization and thought to underlie the migraine aura
      and possibly headache. Here, we tested whether caffeine, known to alleviate or
      trigger headache after acute exposure or chronic use/withdrawal, respectively,
      modulates CSD. We injected C57BL/6J mice with caffeine (30, 60, or 120 mg/kg;
      i.p.) once (acute) or twice per day for one or two weeks (chronic).
      Susceptibility to CSD was evaluated by measuring the electrical CSD threshold and
      by assessing KCl-induced CSD. Simultaneous laser Doppler flowmetry was used to
      assess CSD-induced cortical blood flow changes. Recordings were performed 15 min
      after caffeine/vehicle administration, or 24 h after the last dose of chronic
      caffeine in the withdrawal group. The latter paradigm was also tested in mice
      carrying the familial hemiplegic migraine type 1 R192Q missense mutation,
      considered a valid migraine model. Neither acute/chronic administration nor
      withdrawal of caffeine affected CSD susceptibility or related cortical blood flow
      changes, either in WT or R192Q mice. Hence, adverse or beneficial effects of
      caffeine on headache seem unrelated to CSD pathophysiology, consistent with the
      non-migrainous clinical presentation of caffeine-related headache.

PMID- 29651898
TI  - The effectiveness of therapeutic strategies for patients with radiculopathy: A
      network meta-analysis.
AB  - Objectives The aim of this network meta-analysis is to assess the effectiveness
      of therapeutic strategies for patients with radiculopathy, including physical,
      medical, surgical, and other therapies. Methods We electronically searched
      electronic databases including PubMed and Embase for randomized controlled
      trials. The response rate and visual analog scale of pain change were considered
      as primary outcomes. The outcomes were measured by odds ratio (OR) value and
      corresponding 95% credible intervals (CrIs) or standardized mean difference (MD)
      with 95% CrIs. Besides, surface under cumulative ranking curve (SUCRA) were
      performed to rank efficacy and safety of treatments on each end points. Results A
      total of 16 eligible studies with 1071 subjects were included in this analysis.
      Our results showed that corticosteroid was significantly more effective than
      control regarding the response rate (OR = 3.86, 95% CrI: 1.16, 12.55). Surgery
      had a better performance in pain change compared with control (MD = -1.92, 95%
      CrI: -3.58, -0.15). According to the SUCRA results, corticosteroid, collar, and
      physiotherapy ranked the highest concerning response rate (SUCRA = 0.656, 0.652,
      and 0.610, respectively). Surgery, traction, and corticosteroid were superior to
      others in pain change (SUCRA = 0.866, 0.748, and 0.589, respectively). Conclusion
      According to the network meta-analysis result, we recommended surgery as the
      optimal treatment for radiculopathy patients; traction and corticosteroids were
      also recommended for their beneficial interventions.

PMID- 29651900
TI  - Encounters With Health-Care Providers and Advance Directive Completion by Older
      Adults.
AB  - BACKGROUND: The Patient Self-Determination Act (PSDA) requires hospitals, home
      health agencies, nursing homes, and hospice providers to offer new patients
      information about advance directives. There is little evidence regarding whether
      encounters with these health-care providers prompt advance directive completion
      by patients. OBJECTIVE: To examine whether encounters with various types of
      health-care providers were associated with higher odds of completing advance
      directives by older patients. METHOD: Logistic regression using longitudinal data
      from the 2012 and 2014 waves of the Health and Retirement Study. Participants
      were 3752 US adults aged 65 and older who reported not possessing advance
      directives in 2012. Advance directive was defined as a living will and/or durable
      power of attorney for health care. Four binary variables measured whether
      participants had spent at least 1 night in a hospital, underwent outpatient
      surgery, received home health or hospice care, or spent at least one night in a
      nursing home between 2012 and 2014. RESULTS: Older adults who received hospital,
      nursing home, or home health/hospice care were more likely to complete advance
      directives. Outpatient surgery was not associated with advance directive
      completion. CONCLUSIONS: Older adults with no advance directive in 2012 who
      encountered health-care providers covered by the PSDA were more likely to have
      advance directives by 2014. The exception was outpatient surgery which is
      frequently provided in freestanding surgery centers not subject to PSDA mandates.
      It may be time to consider amending the PSDA to cover freestanding surgery
      centers.

PMID- 29651901
TI  - [Outpatient care for mentally traumatized children and adolescents in Germany].

PMID- 29651902
TI  - Shoulder and Lower Back Joint Reaction Forces in Seated Double Poling.
AB  - Overuse injuries in the shoulders and lower back are hypothesized to be common in
      cross-country sit-skiing. Athletes with reduced trunk muscle control mainly sit
      with the knees higher than the hips (KH). To reduce spinal flexion, a position
      with the knees below the hips (KL) was enabled for these athletes using a frontal
      trunk support. The aim of the study was to compare the shoulder joint
      (glenohumeral joint) and L4-L5 joint reactions of the KL and KH sitting
      positions. Five able-bodied female athletes performed submaximal and maximal
      exercise tests in the sitting positions KL and KH on a ski ergometer. Measured
      pole forces and 3-dimensional kinematics served as input for inverse-dynamics
      simulations to compute the muscle forces and joint reactions in the shoulder and
      L4-L5 joint. This was the first musculoskeletal simulation study of seated double
      poling. The results showed that the KH position was favorable for higher
      performance and decreased values of the shoulder joint reactions for female able
      bodied athletes with full trunk control. The KL position was favorable for lower
      L4-L5 joint reactions and might therefore reduce the risk of lower back injuries.
      These results indicate that it is hard to optimize both performance and safety in
      the same sit-ski.

PMID- 29651903
TI  - The Kinetics of Swinging a Baseball Bat.
AB  - The purpose of this study was to compute the 3-dimensional kinetics required to
      swing 3 youth baseball bats of varying moments of inertia. The 306 swings by 22
      male players (age 13-18 y) were analyzed. Inverse dynamics with respect to the
      batter's hands were computed given the known kinematics and physical properties
      of the bats. Peak force increased with larger bat moments of inertia and was
      strongly correlated with bat tip speed. By contrast, peak moments were weakly
      correlated with bat moments of inertia and bat tip speed. Throughout the swing,
      the force applied to the bat was dominated by a component aligned with the long
      axis of the bat and directed away from the bat knob, whereas the moment applied
      to the bat was minimal until just prior to ball impact. These results indicate
      that players act to mostly "pull" the bat during their swing until just prior to
      ball impact, at which point they rapidly increase the moment on the bat. This
      kinetic analysis provides novel insight into the forces and moments used to swing
      baseball bats.

PMID- 29651904
TI  - Adaptor protein 1 B mu subunit does not contribute to the recycling of kAE1
      protein in polarized renal epithelial cells.
AB  - Mutations in the gene encoding the kidney anion exchanger 1 (kAE1) can lead to
      distal renal tubular acidosis (dRTA). dRTA mutations reported within the carboxyl
      (C)-terminal tail of kAE1 result in apical mis-targeting of the exchanger in
      polarized renal epithelial cells. As kAE1 physically interacts with the MU
      subunit of epithelial adaptor protein 1 B (AP-1B), we investigated the role of
      heterologously expressed MU1B subunit of the AP-1B complex for kAE1 retention to
      the basolateral membrane in polarized porcine LLC-PK1 renal epithelial cells that
      are devoid of endogenous AP-1B. We confirmed the interaction and close proximity
      between kAE1 and MU1B using immunoprecipitation and proximity ligation assay,
      respectively. Expressing the human MU1B subunit in these cells decreased
      significantly the amount of cell surface kAE1 at the steady state, but had no
      significant effect on kAE1 recycling and endocytosis. We show that (i)
      heterologous expression of MU1B displaces the physical interaction of endogenous
      GAPDH with kAE1 WT supporting that both AP-1B and GAPDH proteins bind to an
      overlapping site on kAE1 and (ii) phosphorylation of tyrosine 904 within the
      potential YDEV interaction motif does not alter the kAE1/AP-1B interaction. We
      conclude that MU1B subunit is not involved in recycling of kAE1.

PMID- 29651905
TI  - The intracavitary electrocardiography method for tip location of jugular internal
      vein access device in infants of less than 5 kg: A pilot study.
AB  - PURPOSE:: This is a prospective observational study conducted by neonatologists
      in neonatal intensive care unit from Sant'Anna and San Sebastiano Hospital,
      Caserta, Italy. The objective of the study is to verify the feasibility of
      intracavitary electrocardiography method for tip location of central venous
      access device in infants of less than 5 kg and evaluate the accuracy of the
      method in comparison with post-procedural echocardiographical verification of the
      tip position. PATIENTS AND METHODS:: We enrolled 27 patients weighted between
      0.660 and 5 kg, requiring central vascular access. Ultrasound-guided jugular
      internal vein access was used and after cannulation, we applied the intracavitary
      electrocardiography for tip location as well as post-procedural echocardiography.
      RESULTS:: No significant complication related to intracavitary
      electrocardiography occurred in the studied infants. The increase in P wave on
      intracavitary electrocardiography was detected in all cases (27/27). In only one
      case (false positive), the catheter had the tip out of cavoatrial junction-target
      zone (to post-procedural echocardiography). CONCLUSION:: The intracavitary
      electrocardiography method for tip location of central venous access device is
      safe and accurate in infants, as demonstrated by post-procedural comparative
      echocardiographic controls. As an alternative to echocardiography, not always
      achievable, the diffusion of intracavitary electrocardiography method could
      reduce X-ray exposition and complications of a malpositioned tip.

PMID- 29651906
TI  - Return to Sport Rates in Physically Active Individuals 6 Months After Arthroscopy
      for Femoroacetabular Impingement Syndrome.
AB  - CONTEXT: Six months is the expected time frame to return to sport (RTS) after hip
      arthroscopy for femoroacetabular impingement syndrome (FAIS). OBJECTIVE: The
      primary aims of this study were to (1) report the RTS rate of physically active
      individuals 6 months after arthroscopic surgery for FAIS and (2) compare the self
      reported hip function between those who were able to RTS against those who had
      not. DESIGN: Cohort study. SETTING: The Ohio State University Wexner Medical
      Center. PATIENTS: A total of 42 physically active individuals scheduled for hip
      arthroscopy for FAIS. MAIN OUTCOME MEASURES: Self-reported function, including
      preinjury and current activity levels and ability to participate in sport, were
      collected on 42 individuals with FAIS prior to surgery and at 6-month follow-up.
      Participants were allocated into 2 groups based on self-reported RTS status at 6
      month follow-up. Separate 2-way analyses of variance were used to test the
      interaction of groups (those who did/did not RTS). Main effects were reported in
      the absence of statistically significant interactions (P <= .05). RESULTS:
      Altogether, 28 of 42 participants (66%) returned for 6-month follow-up; 5 of the
      14 participants (35.7%) lost to follow-up underwent contralateral hip surgery
      within the study time frame. At the 6-month follow-up, 16 of the remaining 28
      participants (57.1%) reported that they had returned to sport, 5 of whom returned
      at their prior level of participation. There was no statistically significant
      interaction of group and time for either hip outcome score subscale (P >= .20).
      Self-reported hip function improved over time, regardless of group (P <= .001).
      Participants in the yRTS group demonstrated higher hip outcome score-sport scores
      than did the nRTS group, regardless of time (P = .04). CONCLUSIONS: Though just
      over half of participants returned to sport 6 months after hip arthroscopy for
      FAIS, only 18% returned to their previous level of sports participation.
      Participants who returned to sport reported better function than those who did
      not, but self-reported hip function improved over time regardless of group. The
      most commonly reported reasons for not returning to sport were weakness (69.6%),
      fear (65.2%), and pain (56.5%).

PMID- 29651907
TI  - Evidence-based clinical practice guideline for adult Still's disease.
AB  - OBJECTIVES: Using an expert- and data-driven methodology, we have constructed the
      first clinical practice guidelines (CPGs) for adult Still's disease (ASD) after
      complete systematic review (SR) of the literature based upon the Medical
      Information Network Distribution Service (Minds) procedure. METHODS: The CPG
      committee for ASD organized by the Research Team for Autoimmune Diseases, the
      Research Program for Intractable Disease of the Japanese Ministry of Health,
      Labour, and Welfare has developed CPG for ASD 2017, according to the procedure
      proposed by Minds. The CPG development process includes (1) clarification of the
      purpose of CPG, (2) organization of the steering committee, (3) organization of
      the CPG committee and secretariat, (4) defining the scope (setting of clinical
      questions (CQs)), (5) SR, (6) development of recommendations, (7) drafting the
      CPG, (8) external evaluation and public comments, and (9) release. Because we
      wanted to construct CPG for ASD to encompass both adult-onset Still's disease
      (AOSD) and adult patients with systemic juvenile idiopathic arthritis (sJIA), we
      also included SR data from sJIA in this study. RESULTS: Twenty-six CQs were
      selected and roughly divided into the following items: (1) clinical findings (CQs
      1-4), (2) laboratory findings (CQs 5-8), (3) complications (CQs 9-13), (4)
      treatment with oral medicine (CQs 14-19), (5) treatment with biological reagents
      (CQs 20-23), and (6) treatments for sJIA (CQs 25-26). Recommendations and the
      strength of the recommendations for these CQs were decided by a modified Delphi
      method. CONCLUSION: We have developed the first published CPG for ASD including
      AOSD and sJIA, which includes 26 CQs and recommendations. This guideline will
      help rheumatologists, non-specialized physicians, other healthcare providers,
      medical and health-related students, and patients and their family members to
      understand and treat ASD.

PMID- 29651908
TI  - Design of Eccentric Training System Based on Multiple-Input Single-Output Wiener
      Nonlinear Model.
AB  - OBJECTIVES: The efficacy of eccentric cycling has been proved in research,
      clinical, and sport training activities. However, several constraints make it
      difficult to use commercially available eccentric cycle ergometers. This study
      will stimulate the application of eccentric cycling as an exercise modality.
      STUDY DESIGN: University research laboratory. METHODS: In this study, the
      multiple-input single-output (MISO) Wiener nonlinear model was applied to the
      design of the eccentric training system. Particle Swarm Optimization (PSO)
      algorithm was then applied to identify the parameters of the MISO Wiener
      nonlinear model. The computer software embedded with MISO model was programmed
      for not only controlling and monitoring the running status of the eccentric
      training system, but also collecting data in a flexible and convenient manner.
      RESULTS: The correlation coefficient of 0.9985 and root mean square error of
      3.3264 between the collected power value and the estimated power value from the
      model shows the good performance of the model. CONCLUSION: The proposed method
      for the design of the eccentric training system using MISO Wiener nonlinear model
      provides a new way for eccentric research and training.

PMID- 29651909
TI  - [Anorexia nervosa in males].
AB  - Anorexia nervosa in males Abstract. Anorexia nervosa (AN) is a rare disorder in
      boys and men with limited data and studies available. The recent update of the
      Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) will
      in all likelihood lead to an increase in the prevalence of AN in boys and men.
      This study aims to give an overview of the existing data in regards to gender
      differences in epidemiology, etiology, and symptoms of AN. We aim to highlight
      the differences in AN between the sexes, from a clinical point of view, and
      underline the need for further research on AN in boys.

PMID- 29651910
TI  - Head Impact Exposure in Practices Correlates With Exposure in Games for Youth
      Football Players.
AB  - This study aimed to compare head impact exposures between practices and games in
      football players ages 9 to 14 years, who account for approximately 70% of all
      football players in the United States. Over a period of 2 seasons, 136 players
      were enrolled from 3 youth programs, and 49,847 head impacts were recorded from
      345 practices and 137 games. During the study, individual players sustained a
      median of 211 impacts per season, with a maximum of 1226 impacts. Players
      sustained 50th (95th) percentile peak linear acceleration of 18.3 (46.9) g, peak
      rotational acceleration of 1305.4 (3316.6) rad.s-2, and Head Impact Technology
      Severity Profile of 13.7 (24.3), respectively. Overall, players with a higher
      frequency of head impacts at practices recorded a higher frequency of head
      impacts at games (P < .001, r2 = .52), and players who sustained a greater
      average magnitude of head impacts during practice also recorded a greater average
      magnitude of head impacts during games (P < .001). The youth football head impact
      data quantified in this study provide valuable insight into the player exposure
      profile, which should serve as a key baseline in efforts to reduce injury.

PMID- 29651911
TI  - The Effect of Diacutaneous Fibrolysis on Patellar Position Measured Using
      Ultrasound Scanning in Patellofemoral Pain Syndrome Patients.
AB  - CONTEXT: Tightness or lack of flexibility of flexibility of several muscles of
      the thigh has been associated with patellofemoral-join pain. A tight iliotibial
      band can lead to laterally located patella and an abnormal patellar tracking
      pattern. Diacutaneous fibrolysis is commonly used to reduce muscle tightness, but
      no studies have evaluated the effects of this technique in the treatment of
      patellofemoral pain syndrome patients. OBJECTIVE: To assess the effect of
      diacutaneous fibrolysis on patellar position in patients with patellofemoral pain
      syndrome. DESIGN: A single-group, pretest-posttest clinical trial. SETTING:
      University of Zaragoza. PARTICIPANTS: 46 subjects with patellofemoral pain (20
      males, 26 females (age 27.8 +/- 6.9 years)). INTERVENTION: 3 sessions of
      diacutaneous fibrolysis. MAIN OUTCOME MEASURES: Patellar position measurement
      using real time ultrasound scanning, pain intensity measured with visual analogue
      scale and function measured with the Anterior Knee Pain Scale. RESULTS: The
      application of three sessions of diacutaneous fibrolysis significantly increased
      the patellar position at post-treatment evaluation (p<0.001) and at one-week
      follow-up (p<0.001). There was not a significance difference on patellar position
      between post-treatment and follow-up measurements (p=0.283). There were also a
      statistically significant decrease in pain and increase in function at post
      treatment and at one-week follow-up measurements (p<0.001). CONCLUSION: This
      study found that patellar position, pain intensity and function were
      significantly improved after three sessions of diacutaneous fibrolysis and at one
      week follow up.

PMID- 29651912
TI  - Effects of diclofenac on the pharmacokinetics of celastrol in rats and its
      transport.
AB  - CONTEXT: Diclofenac and celastrol are always used together for the treatment of
      rheumatoid arthritis; the herb-drug interaction potential between diclofenac and
      celastrol is still unknown. OBJECTIVE: This study investigates the effects of
      diclofenac on the pharmacokinetics of celastrol in rats. MATERIALS AND METHODS:
      Twelve male Sprague-Dawley rats were divided into two groups and received
      celastrol (1 mg/kg) or both celastrol (1 mg/kg) and diclofenac (10 mg/kg) by oral
      gavage, and blood samples were collected via the oculi chorioideae vein and
      determined using the LC-MS method developed in this study. Additionally, the
      effects of diclofenac on the transport of celastrol were investigated using a
      Caco-2 cell transwell model. RESULTS: Diclofenac could significantly (p < 0.05)
      decrease the Cmax (from 66.93 +/- 10.28 to 41.25 +/- 8.06 ng/mL) and AUC0-t (from
      765.84 +/- 163.61 to 451.33 +/- 110.88 MUg * h/L) of celastrol in rats. The
      efflux ratio of celastrol increased significantly (p < 0.05) from 3.12 to 4.55
      with the treatment of diclofenac. DISCUSSION AND CONCLUSION: These results
      indicated that diclofenac could decrease the system exposure of celastrol in rats
      when they are co-administered, and these effects might be exerted via decreasing
      its absorption in intestine.

PMID- 29651913
TI  - Drug importation into Italy by body packing: An analysis of the UNODC Individual
      Drug Seizures Database.
AB  - Internal concealment and transportation of illegal substances by body packing is
      a major business with very high profits, attracting criminals all over the world.
      As body packers are rarely arrested, it is difficult to quantify their proportion
      in the general population and, consequently, identify the countries involved in
      this kind of drug traffic; as a consequence, the percentage of undetected cases
      is undoubtedly high. The aim of this study is to provide useful information
      concerning the country of origin of body packers travelling to Italy through the
      analysis of the United Nations Office on Drugs and Crime Individual Drug Seizures
      Report database in the period 2010-2015. Results of our study highlighted a total
      of 85 cases, producing a total of 52.4 kg of drugs transported through body
      packing towards Italy. Data obtained from our analysis could represent an useful
      starting point to: (a) enhance police controls on people coming from targeted
      countries and improve collaborations between Italian Police Forces and those of
      other countries; (b) understand the reason why some cities/airports are so
      frequently used in drug trafficking through body packing and, as a consequence,
      enhance police controls in these places; and

PMID- 29651914
TI  - Inflammatory pathways are central to posterior cerebrovascular artery remodelling
      prior to the onset of congenital hypertension.
AB  - Cerebral artery hypoperfusion may provide the basis for linking ischemic stroke
      with hypertension. Brain hypoperfusion may induce hypertension that may serve as
      an auto-protective mechanism to prevent ischemic stroke. We hypothesised that
      hypertension is caused by remodelling of the cerebral arteries, which is
      triggered by inflammation. We used a congenital rat model of hypertension and
      examined age-related changes in gene expression of the cerebral arteries using
      RNA sequencing. Prior to hypertension, we found changes in signalling pathways
      associated with the immune system and fibrosis. Validation studies using second
      harmonics generation microscopy revealed upregulation of collagen type I and IV
      in both tunica externa and media. These changes in the extracellular matrix of
      cerebral arteries pre-empted hypertension accounting for their increased
      stiffness and resistance, both potentially conducive to stroke. These data
      indicate that inflammatory driven cerebral artery remodelling occurs prior to the
      onset of hypertension and may be a trigger elevating systemic blood pressure in
      genetically programmed hypertension.

PMID- 29651915
TI  - Intravenous radiographic contrast administered prior to high-dose methotrexate
      and subsequent toxicity requiring the use of glucarpidase.
AB  - Methotrexate is a dihydrofolate reductase inhibitor that interferes with DNA
      synthesis, DNA repair, and cellular replication. We present the first adult case
      of a patient who received intravenous contrast prior to administration of high
      dose methotrexate, who subsequently experienced delayed methotrexate clearance
      and renal impairment necessitating the use of glucarpidase. This case displays a
      possible correlation between intravenous radiographic contrast administration and
      resulting toxicity due to delayed methotrexate clearance.

PMID- 29651916
TI  - Assessment of exposure risk of irinotecan and its active metabolite, SN-38,
      through perspiration during chemotherapy.
AB  - Background Irinotecan (CPT-11) is the key drug used in chemotherapy for many
      malignant tumors. CPT-11 has cholinergic activity and induces perspiration during
      intravenous administration. In this study, concentrations of CPT-11 and its
      active metabolite, SN-38, released during perspiration were measured and risk of
      exposure of these drugs was assessed. Method Beads of sweat were collected using
      a dropper from four patients undergoing a chemotherapy regimen involving
      intravenous administration of CPT-11. The concentrations of CPT-11 and SN-38 in
      sweat were measured using liquid chromatography tandem mass spectrometry. Result
      Chemotherapy regimens were capecitabine and irinotecan plus bevacizumab (n = 1),
      CPT-11 monotherapy (n = 1), and oxaliplatin-irinotecan-leucovorin-5-fluorouracil
      (n = 2). Uridine diphosphate-glucuronosyltransferase 1A1 phenotypes were *6 homo
      type (n = 1), *6 hetero-type (n = 1), and wild type (n = 2). CPT-11 dose was
      292.3 +/- 75.5 mg/body weight (mean +/- standard deviation). CPT-11 was detected
      in sweat secreted by all the four patients, and its mean (+/-standard deviation)
      concentration was 252.6 (+/-111.9) ng/ml. SN-38 was detected in only one of the
      patients who received oxaliplatin-irinotecan-leucovorin-5-fluorouracil treatment
      and who had the wild-type uridine diphosphate-glucuronosyltransferase 1A1
      phenotype at a concentration of 74.37 ng/ml. Conclusion CPT-11 and SN-38 are
      detected in sweat released during intravenous CPT-11 administration. Beads of
      sweat or linen clothes that absorb the sweat might be the source of CPT-11 and SN
      38 exposure.

PMID- 29651917
TI  - Erythematous skin lesions with necrotic centers on lower extremities due to the
      use of ruxolitinib for primary myelofibrosis.
AB  - Ruxolitinib is a small molecule JAK-2 inhibitor approved for the treatment of
      certain myeloproliferative neoplasms. Ruxolitinib-related skin toxicity is
      extremely rare. We report herein an unusual erythematous skin eruption with
      necrotic centers involving lower extremities in a patient with primary
      myelofibrosis treated with ruxolitinib. Awareness of this unusual skin toxicity
      with ruxolitinib becomes even more important as JAK-2 inhibition might soon find
      clinical applications in dermatology.

PMID- 29651918
TI  - Updated report on incidence of infusion-site reactions associated with peripheral
      intravenous administration of fosaprepitant.
AB  - Purpose Fosaprepitant (Emend(r)) is an antiemetic frequently used for the
      prevention of chemotherapy-induced nausea and vomiting. We previously documented
      an overall 28.7% incidence of infusion-site reactions in patients receiving
      fosaprepitant via peripheral venous access. These data resulted in a practice
      change within our institution; fosaprepitant is administered in more dilute
      concentrations over 30 min to prevent these adverse events. This retrospective
      study explored the impact of this practice change on the incidence of infusion
      site reactions. Methods Medical records of patients with cancer receiving
      intravenous fosaprepitant through a peripheral intravenous line were reviewed.
      The primary objective of this study was to compare the incidence of infusion-site
      reactions before the practice change to the incidence after the practice change.
      Data collection included demographics, fosaprepitant infusion information, and
      grading of reactions. Results Between September 2013 and December of 2013, charts
      of 122 patients receiving intravenous fosaprepitant through a peripheral line at
      the The Arthur G. James Cancer Hospital at The Ohio State University were
      reviewed. We found a 5.74% incidence of infusion-site reactions which is
      significantly lower than the prechange incidence of 28.7% (p < 0.001).
      Conclusions Infusion-site reactions were significantly reduced when fosaprepitant
      was diluted to 150 mg/250 ml and infused over 30 min. We recommend oncology
      pharmacists consider using the more dilute fosaprepitant preparation and 30 min
      infusion duration when administering via a peripheral intravenous line to improve
      patient tolerance.

PMID- 29651919
TI  - The incidence and timing of leukocyte overshoot after pegfilgrastim
      administration.
AB  - Introduction Pegfilgrastim is a PEGylated formulation of filgrastim with a long
      half-life. It is highly convenient and less burdensome for patients. However,
      white blood cell count may temporarily increase after administration; in
      particular, a leukocyte overshoot may be observed. The present study
      retrospectively examined the incidence and timing of leukocyte overshoot after
      pegfilgrastim administration. Patients and methods Fifty-five patients (118
      occasions of pegfilgrastim) were evaluated. Leukocyte overshoot was defined as
      white blood cell count >=10,000/mm3 exceeding the reference value. Results
      Leukocyte overshoot was observed in 71.2% (84/118) occasions, in 76.4% (42/55)
      patients. The maximum white blood cell count >=30,000/mm3 was observed in 30.5%
      (36/118) occasions in 45.5% (25/55) patients and was observed in 39.3% (33/84)
      occasions on day 1 after pegfilgrastim administration and 26.2% (22/84) on day 2.
      Leukocyte overshoot has been observed in only 23.1% (9/39) patients administered
      with normal granulocyte colony-stimulating factor. However, there were no
      patients with white blood cell counts >=30,000/mm3. Conclusion There was a higher
      frequency of occurrence of leukocyte overshoot in response to pegfilgrastim than
      in response to normal granulocyte colony-stimulating factor. High incidence of
      leukocyte overshoot was observed when blood was collected 1-2 days after
      administration of pegfilgrastim. It is important for patients to understand the
      characteristics of pegfilgrastim by conducting pharmaceutical guidance.

PMID- 29651920
TI  - Systemic Factors Associated With Prosocial Skills and Maladaptive Functioning in
      Youth Exposed to Intimate Partner Violence.
AB  - Children are frequently present in homes in which intimate partner violence (IPV)
      occurs. Following exposure to IPV, children may develop behavioral health
      difficulties, struggle with regulating emotions, or exhibit aggression. Despite
      the negative outcomes associated with witnessing IPV, many children also display
      resilience. Guided by Bronfenbrenner's bioecological model, this study examined
      person-level, process-level (microsystem), and context-level (mesosystem) factors
      associated with positive and negative functioning among youth exposed to IPV.
      Participants were 118 mothers who reported on their 6- to 14-year-old children.
      All mothers experienced severe physical, psychological, and/or sexual IPV in the
      past 6 months. Linear regression modeling was conducted separately for youth
      maladaptive functioning and prosocial skills. The linear regression model for
      maladaptive functioning was significant, F(6, 110) = 9.32, p < .001, adj R2 =
      27%, with more severe IPV (beta = .18, p < .05) and more negative parenting
      practices (beta = .34, p < .001) associated with worse child outcomes. The model
      for prosocial skills was also significant, F(6, 110) = 3.34, p < .01, adj. R2 =
      14%, with less negative parenting practices (beta = -.26, p < .001) and greater
      community connectedness (beta = .17, p < .05) linked to more prosocial skills.
      These findings provide critical knowledge on specific mutable factors associated
      with positive and negative functioning among children in the context of IPV
      exposure. Such factors could be incorporated into strength-based interventions
      following family violence.

PMID- 29651921
TI  - Jordanian Men's and Women's Attitudes Toward Intimate Partner Violence and Its
      Correlates With Family Functioning and Demographics.
AB  - Jordan is a developing country in the Middle East and, much like other countries
      in the world, has high rates of intimate partner violence (IPV). Little
      information is available on Jordanian men's and women's attitudes toward IPV. The
      purpose of this study is to examine men's and women's attitudes toward IPV in
      Jordan and its relationship with some demographics and family functioning. A
      descriptive cross-sectional correlational design with a sample of 401 men and
      women was used. Descriptive statistics ( M, SD), Pearson r, t test, and ANOVA
      were used. The results indicated that Jordanian men and women have a lower score
      of IPVAS, 40.06 ( SD = 8.20), indicating lower acceptance of IPV compared with
      the literature. Family functioning was 3.12 ( SD = 0.46), indicating more healthy
      families. Family functioning was negatively correlated with IPVAS scores ( r = 
      .22, p = .00). All demographic variables showed small to moderate correlations
      with IPVAS. Education for both study participants and their spouses had a
      negative correlation with IPVAS ( r = -.27, p = .00) and ( r = -.20, p = .00),
      respectively. Male participants, individuals who were living with extended
      family, and those living in rural areas had significantly high IPVAS scores,
      indicating more accepting attitudes toward IPV. Practitioners should provide
      families with education on the methods of conflict resolution, effective
      communication within the family, problem-solving approaches, equal role
      distribution, and appropriate styles of establishing a family.

PMID- 29651922
TI  - Prior Exposure to Intimate Partner Violence Associated With Less HIV Testing
      Among Young Women.
AB  - Low-income minority women are disproportionately represented among those living
      with HIV in the United States. They are also at risk for the SAVA (substance
      abuse, violence, and HIV/AIDS) syndemic issues. Women who have recently given
      birth are at high risk for substance use and intimate partner violence (IPV), and
      HIV testing is not routinely administered during the postpartum visit. We
      explored the relationship between substance use, IPV, and HIV testing among low
      income young adult women attending Special Supplemental Nutrition Program for
      Women, Infants, and Children (WIC), a federally supported nutrition program. A
      survey assessed substance use, relationships in particular with violence
      exposure, and HIV testing behavior in the past 6 months among a convenience
      sample of 100 women aged 18 to 30. The survey was conducted at several WIC
      offices in an urban setting in the Mid-Atlantic region between June and December
      2015. Physical violence was the only IPV variable significantly associated ( p =
      .022) with not being tested for HIV in the past 6 months, remaining significant
      even after adjusting for demographic and other significant variables (adjusted
      odds ratio [AOR] = 0.02; 95% confidence interval [CI] = [0.00, 0.41]). Women
      exposed to physical IPV or psychological IPV in the past year were significantly
      more likely to have ever used an illicit drug (physical IPV: 34% vs. 59%, p =
      .052; psychological IPV: 22% vs. 53%. p = .002). These findings between physical
      IPV and HIV testing history highlight the need to further understand how the
      context of violence affects HIV testing behaviors. Providing convenient, safe,
      and accessible HIV testing sites in spaces like WIC may increase HIV testing
      rates overall and specifically among women experiencing IPV.

PMID- 29651923
TI  - Identification of Domestic Violence Service Needs Among Child Welfare-Involved
      Parents With Substance Use Disorders: A Gender-Stratified Analysis.
AB  - The current study examined the prevalence and associations of a need for domestic
      violence services among child welfare-involved mothers and fathers with substance
      use disorders. Data were drawn from 2,231 child welfare-involved parents in
      Illinois with an identified substance use disorder. Approximately 42% of mothers
      and 33% of fathers with a substance use disorder had a concurrent need for
      domestic violence services. The sample was stratified by gender and logistic
      regression models were fit to determine the adjusted odds of an identified need
      for domestic violence services. For both mothers and fathers, the strongest
      association was an additional need for mental health services. Age, education
      status, alcohol use, marijuana use, and a reported history of physical violence
      victimization were also associated with a need for domestic violence services
      among mothers, while race, age, marital status, annual income, alcohol use,
      cocaine use, and a reported history of physical violence perpetration were
      associated with a need for domestic violence services among fathers. The findings
      of this study make clear that domestic violence is a commonly co-occurring
      service need for child welfare-involved parents with identified substance use
      disorders, and that associations with this need vary by gender.

PMID- 29651924
TI  - Abuse of Rural Elders in Mansoura Districts, Dakahlia, Egypt: Prevalence, Types,
      Risk Factors, and Lifestyle.
AB  - This study was carried out to explore the prevalence of elderly abuse, identify
      its types, associated risk factors and determine quality of their life in Rural
      Mansoura districts, Egypt. A cross-section study was conducted on a sample of 272
      elders recruited from outpatient clinicsFamily Health Centers in Shawa & Berkin
      villages from May 1 to September 3, 2016. 200 (73.5%) elders accepted
      participation. A previously designed and validated questionnaires were used to
      collect data from participants. 46% of the studied elders were abused. The most
      frequent forms of abuse were negligence (40%) followed by psychological abuse
      (30.5%). Abuse was significantly higher among females (56.5%), farmers (67.2%),
      illiterates (55.5%) and living alone elders (68.5%). Elders with chronic diseases
      were significantly more abused (54.9%) especially diabetic and hypertensive
      elders (71.4%). Concerning lifestyle of the studied elders, 21% of them had bad
      health perception generally. The study showed that dependent elders exposed
      significantly to higher rates of abuse than independents with highly statistical
      significant.Logistic regression analysis revealed that being a female and
      previously working as farmer are 2.5 and 4.6 times more likely to be abused. On
      the other hand, sharing house with other partner or offspring and absence of
      chronic diseases are protective predictors against elder abuse. Governmental and
      NGOS support to elders in rural areas especially females and famers is highly
      recommended. Health insurance is necessary for health promotion, reduction of
      chronic disease and or disability to decrease dependency is crucial.

PMID- 29651925
TI  - Heptamer Peptide Disassembles Native Amyloid in Human Plasma Through Heat Shock
      Protein 70.
AB  - Proteostasis, which includes the repair and disposal of misfolded proteins,
      depends, in part, on the activity of heat shock proteins (HSPs), a well-known
      class of chaperone molecules. When this process fails, abnormally folded proteins
      may accumulate in cells, tissues, and blood. These species are a hallmark of
      protein aggregation diseases, but also amass during aging, often in the absence
      of an identified clinical disorder. We report that a neuroprotective cyclic
      heptapeptide, CHEC-7, which has been applied systemically as a therapeutic in
      animal neurodegeneration models, disrupts such aggregates and inhibits
      amyloidogenesis when added in nanomolar concentrations to human plasma. This
      effect includes aggregates of amyloid beta (Abeta1-40, 1-42), prominent features
      of Alzheimer's disease pathology. The activity of endogenous HSP70, a recently
      discovered target of the peptide, is required as demonstrated by both antibody
      blocking and application of pifithrin-MU, an HSP70 inhibitor. CHEC-7 is the first
      high-affinity compound to stimulate HSP70's disaggregase activity and therefore
      enable this endogenous mechanism in a human systemic environment, increasing the
      likelihood of a convenient therapy for protein aggregate disease, including age
      related failures of protein repair.

PMID- 29651926
TI  - Nine months a slave: when pregnancy is involuntary servitude to a foetus.
AB  - Recent globally compiled evidence suggests that one-quarter of pregnancies end in
      abortions. However, abortions remain illegal in many countries, resulting in
      unsafe practices. Debates have largely stalled with the pro-life, pro-choice
      epithets. To provide further arguments in support of legalising abortion
      services, we argue that the state cannot demand of a woman that she maintains an
      unwanted pregnancy because that demand places her in a state of involuntary
      servitude. Involuntary servitude would put states in breach of international
      human rights law (Article 8 of International Covenant on Civil and Political
      Rights). Furthermore, we argue that the fact that a life may be forfeit when a
      woman withdraws her service is no basis for enforcing the servitude. We draw on
      the 13th Amendment of the US Constitution as an example to extend the argument
      and highlight the need to test involuntary servitude in international human
      rights law through mechanisms offered in the international periodic review of
      member states. This could provide a robust approach to support and strengthen
      access to safe abortion services.

PMID- 29651927
TI  - A two-stage approach to estimate spatial and spatio-temporal disease risks in the
      presence of local discontinuities and clusters.
AB  - Disease risk maps for areal unit data are often estimated from Poisson mixed
      models with local spatial smoothing, for example by incorporating random effects
      with a conditional autoregressive prior distribution. However, one of the
      limitations is that local discontinuities in the spatial pattern are not usually
      modelled, leading to over-smoothing of the risk maps and a masking of clusters of
      hot/coldspot areas. In this paper, we propose a novel two-stage approach to
      estimate and map disease risk in the presence of such local discontinuities and
      clusters. We propose approaches in both spatial and spatio-temporal domains,
      where for the latter the clusters can either be fixed or allowed to vary over
      time. In the first stage, we apply an agglomerative hierarchical clustering
      algorithm to training data to provide sets of potential clusters, and in the
      second stage, a two-level spatial or spatio-temporal model is applied to each
      potential cluster configuration. The superiority of the proposed approach with
      regard to a previous proposal is shown by simulation, and the methodology is
      applied to two important public health problems in Spain, namely stomach cancer
      mortality across Spain and brain cancer incidence in the Navarre and Basque
      Country regions of Spain.

PMID- 29651928
TI  - Rural Postpartum Women With Substance Use Disorders.
AB  - The incidence of perinatal opioid use and neonatal withdrawal continues to rise
      rapidly in the face of the growing opioid addiction epidemic in the United
      States, with rural areas more severely affected. Despite decades of research and
      development of practice guidelines, maternal and neonatal outcomes have not
      improved substantially. This focused ethnography sought to understand the
      experience of accessing care necessary for substance use disorder recovery,
      pregnancy, and parenting. Personal accounts of 13 rural women, supplemented by
      participant observation and media artifacts, uncovered three domains with
      underlying themes: challenges of getting treatment and care (service
      availability, distance/geographic location, transportation, provider
      collaboration/coordination, physical and emotional safety), opportunities to bond
      (proximity, information), and importance of relationships (respect, empathy,
      familiarity, inclusion, interactions with care providers). Findings highlight the
      need for providers and policy makers to reduce barriers to treatment and care
      related to logistics, stigma, judgment, and lack of understanding of perinatal
      addiction.

PMID- 29651929
TI  - Chronic iliofemoral vein obstruction - an under-recognized cause of exercise
      limitation.
AB  - Local symptoms of chronic venous insufficiency after deep vein thrombosis (DVT)
      are well described, but little is known about the effect of residual venous
      obstruction on exercise capacity. We tested our hypothesis that chronic residual
      iliofemoral vein occlusion (IFVO) after DVT may impair exercise capacity. Nine
      post-DVT patients with residual IFVO and effort intolerance were studied; a
      comparison cohort consisted of 11 healthy volunteers. Exercise tolerance was
      assessed by bimodality incremental symptom-limited cardiopulmonary testing, using
      leg and arm ergometers. In healthy subjects, leg vein obstruction was modelled by
      application to the thighs of cuff tourniquets inflated to 30-40 mmHg. Leg
      exercise tolerance as measured by oxygen uptake at peak exercise (peak ?'O2) was
      reduced in patients (median 50% predicted (range 36-83%) vs. 88% predicted (67
      129%) in normal subjects, p < 0.001). Arm exercise tolerance was also reduced in
      patients, but less severely than in the legs - the median arm: leg ratio of peak
      ?'O2 was 0.95 (0.77-1.43) in patients vs. a normal ratio of 0.73 (0.6-1.0) in
      healthy subjects (p < 0.003). In healthy subjects, bilateral leg vein obstruction
      by tourniquets reduced peak ?'O2 in leg exercise to 76% predicted (range 55-108%;
      p < 0.001 vs. standard test). In conclusion, the comparison of arm vs. leg
      exercise capacity in post-DVT patients with residual IFVO and the effect of
      experimental venous obstruction (thigh tourniquets) in healthy subjects suggest
      that reduced exercise capacity in patients was at least partially caused by
      reduced venous return. Chronic venous obstruction should be recognized as a cause
      of exercise limitation.

PMID- 29651930
TI  - Molecular insights into the irreversible mechanical behavior of sickle
      hemoglobin.
AB  - Sickle cell disease is caused by the amino acid substitution of glutamic acid to
      valine, which leads to the polymerization of deoxygenated sickle hemoglobin (HbS)
      into long strands. These strands are responsible for the sickling of red blood
      cells (RBCs), making blood hyper-coagulable leading to an increased chance of
      vaso-occlusive crisis. The conformational changes in sickled RBCs traveling
      through narrow blood vessels in a highly viscous fluid are critical in
      understanding; however, there are few studies that investigate the origins of the
      molecular mechanical behavior of sickled RBCs. In this work, we investigate the
      molecular mechanical properties of HbS molecules. A mechanical model was used to
      estimate the directional stiffness of an HbS molecule and the results were
      compared to adult human hemoglobin (HbA). The comparison shows a significant
      difference in strength between HbS and HbA, as well as anisotropic behavior of
      the hemoglobin molecules. The results also indicated that the HbS molecule
      experienced more irreversible mechanical behavior than HbA under compression.
      Further, we have characterized the elastic and compressive properties of a double
      stranded sickle fiber using six HbS molecules, and it shows that the HbS
      molecules are bound to each other through strong inter-molecular forces.

PMID- 29651931
TI  - Hypertension.

PMID- 29651932
TI  - Alternative Host Models for Testing Anti-Protozoal or Antifungal Compounds and
      Fungal Infection.
AB  - The neglected tropical diseases (NTDs) are caused by several parasites, fungi,
      bacteria and viruses and affect more than one billion people in the world. The
      control and prevention against NTDs need implementation of alternative methods
      for testing new compounds against these diseases. For the implementation of
      alternative methods, it is necessary to apply the principles of replacement,
      reduction and refinement (the 3Rs) for the use of laboratory animals.
      Accordingly, the present review addressed a variety of alternative models to
      study the infections caused by protozoa and fungi. Overall, vertebrate and
      invertebrate models of fungal infection have been used to elucidate host-pathogen
      interactions. However, until now the insect model has not been used in protozoal
      studies as an alternative method, but there is interest in the scientific
      community to try new tools to screen alternative drugs to control and prevent
      protozoal infections.

PMID- 29651933
TI  - Alternative Methods to Animal Studies for the Evaluation of Topical/ Transdermal
      Drug Delivery Systems.
AB  - It is critical to develop an effective understanding of the interaction between
      the drug, delivery system and skin in order to predict and assess skin
      penetration and permeation. Experimental models for the assessment of topical and
      transdermal delivery systems must permit evaluation of these complex
      interactions. Whilst in the past, animal models were commonly used, recent
      regulatory guidelines, based on 3R principles (refinement, reduction,
      replacement), encourage the rational use of animals. Alternative methods have
      been proposed for use in the development of topical and transdermal delivery
      systems which are often used in combination. We will review the current state of
      the art in alternative methods for topical and transdermal delivery systems
      development, including technologies that can assist in the characterization of
      skin penetration/permeation studies.

PMID- 29651934
TI  - Effects of Curcumin on Squamous Cell Carcinoma of Tongue: An In Vitro Study.
AB  - BACKGROUND: The Squamous Cell Carcinoma of the Tongue (TSCC) is the most frequent
      cancer of oral cavity often characterized by poor prognosis. Conventional
      therapies are not very efficient and often may cause serious side effects. In
      this context, introduction of natural substances as possible adjuvant in the
      treatment and prevention of cancer is becoming a relevant topic. In fact,
      curcumin has been used for decades in Chinese traditional medicine for its
      beneficial effects. Curcumin has anticancer properties in many tumors however,
      its action on the tongue carcinoma is not entirely clear and many other
      investigations are necessary. OBJECTIVE: Curcumin seems to be a good adjuvant in
      the treatment of head and neck tumors. However, these studies are generic and
      there are not many specific studies on TSCC, the most frequent and most
      aggressive cancer of the head-neck region. Our goal is to demonstrate its
      effectiveness also for TSCC. METHODS: In this study, we evaluated the effects of
      curcumin on TSCC cells using different concentrations (1, 5, 10, 20 and 50 uM)
      and 3 different treatment times (24, 48 and 72 hours). The inhibition of
      adhesion, proliferation, viability, migration and apoptosis was studied. RESULTS:
      IC50 value of curcumin is about 10 uM and there have been inhibitory effects even
      for treatments at low concentrations. Curcumin reduces migration and progression
      of TSCC cells and it promotes apoptosis and inhibits tumorigenesis. CONCLUSIONS:
      These results suggest the possible use of curcumin as an anti-cancer agent in
      TSCC. However, in vivo studies are needed to confirm these effects and overcome
      its low bioavailability.

PMID- 29651935
TI  - Nicotine Receptors as a Possible Marker for Smoking-related Sperm Damage.
AB  - BACKGROUND: Several studies demonstrate that cigarette smoking has a negative
      effect on the reproductive health of both genders. The mechanisms by which it
      alters male gonadic function are not entirely clear. The combustion of cigarette
      produces a lot of chemical compounds that may be responsible for the negative
      impact of cigarette smoke on sperm parameters. In particular, the effects on
      semen of nicotine, a substance present in the tobacco plant and the main
      constituent of cigarette smoke, have been studied, showing that this alkaloid
      alters sperm parameters. Recently we investigated the mechanism by which nicotine
      damages sperm through the evaluation of the expression of nicotinic receptors
      subunits in human spermatozoa. CONCLUSION: 8 nAChR subunits found to date in
      mammals are expressed in human spermatozoa but, in non-smokers subjects, only
      alpha7 subunit is translated. Cigarette smoking may stimulate the expression of
      some subunits, not translated in non-smokers. Therefore, the presence in sperm of
      other nAChR subunits than alpha7 could represent a marker for smoking-related
      sperm damage.

PMID- 29651936
TI  - Mammalian Sperm Protamine Extraction and Analysis: A Step-By-Step Detailed
      Protocol and Brief Review of Protamine Alterations.
AB  - BACKGROUND: Protamines are the most abundant sperm nuclear proteins and pack
      approximately the 92-98% of the mammalian sperm DNA. In mammals, two types of
      protamines have been described, the Protamine 1 (P1) and the Protamine 2 (P2)
      family. The deregulation of the relative P1/P2 ratio has been correlated to DNA
      damage, alterations in seminal parameters, and low success rate of assisted
      reproduction techniques. Additionally, the extraction and analysis of protamines
      have been important to understand the fundamental aspects of the sperm chromatin
      structure and function, protamine sequence conservation among species, and sperm
      chromatin alterations present in infertile males. However, protamines show a
      particular chemical nature due to its special amino acid sequence, extremely rich
      in arginine and cysteine residues. Because of these peculiar characteristics of
      protamines, their extraction and analysis is not as straightforward as the
      analysis of other chromatin-associated proteins, for which many detailed
      protocols are already available. CONCLUSION: A step-by-step protocol was needed
      to facilitate protamine analysis to researchers interested in their
      implementation. Therefore, in order to contribute to fulfill this need, here we
      provide a detailed protocol, which should be useful to research teams and
      laboratories interested in the protamine field. In addition, we also briefly
      review the different studies published so far on protamine alterations and male
      infertility.

PMID- 29651937
TI  - An Emerging Role of Endometrial Inflammasome in Reproduction: New Therapeutic
      Approaches.
AB  - BACKGROUND: One of the common complications of pregnancy is spontaneous pregnancy
      loss which occurs in an estimated 5- 15% of pregnancies. Of all women 1%-5%
      suffer from Recurrent Pregnancy Loss (RPL). Despite the fact that RPL has been
      associated to various anatomic, hormonal, immune, hematologic, and genetic
      defects, in 30% of the patients, screening tests included in the RPL workup may
      have negative results. Recently, we demonstrated a significant increased
      activation of endometrial NALP-3 inflammasome, and a caspase-1 dependent
      secretion of IL-18 and IL-1beta in the endometrial tissues obtained from RPL
      women compared with a fertile women group. The inflammasome has emerged as a key
      player in innate immunity and inflammation. An abnormal inflammasome activation,
      in absence of detectable infectious causes, might be one of the molecular
      mechanisms involved in establishing an unreceptive endometrium, potentially
      leading to early fetal loss. Upon activation, this multiprotein complex makes
      possible the caspase- 1-mediated proteolytic processing of proinflammatory
      cytokines generating their respective mature secretory forms. CONCLUSION: The
      understanding of molecular modulation of inflammasome associated pathways is
      critical for drug design, development and delivery. To date many promising
      inhibitors of inflammasome complex activation have been described, such as
      MCC950, beta-Hydroxybutyrate or Micro RNAs that affect NALP3 expression and
      activation. Furthermore, several herbal extracts and its bioactive constituents
      have shown to be effective in inflammatory response mediated by NLRP3
      inflammasome activation. Nevertheless all these molecules represent a significant
      progress toward developing therapies that target IL-18 and IL-1beta secretion in
      a variety of diseases.

PMID- 29651938
TI  - Semen Proteomics Reveals the Impact of Enterococcus faecalis on male Fertility.
AB  - BACKGROUND: Infectious etiologies contribute to 15% of male factor infertility.
      Enterococcus faecalis (E. faecalis) is commonly identified in semen culture of
      infertile men and it is associated with significantly poorer semen quality.
      OBJECTIVE: Aim of this study was to identify new seminal biomarkers for the male
      tract infection by E. faecalis, using proteomic profiling, in order to understand
      the effect of E. faecalis on the physiopathology of male reproduction. METHODS:
      We included in the study ten patients seeking medical care for primary
      infertility with prostate-vesicular-epidydimitis and with microbiological
      analysis on semen and/or prostatic secretions positive for E. faecalis. Ten
      fertile men have been enrolled as a control group in the protocol. An aliquot of
      each seminal plasma was subjected to an in-solution digestion protocol and
      analyzed using an Ultimate 3000 RSLCnano HPLC apparatus coupled to a LTQ Orbitrap
      Elite mass spectrometer. RESULTS: Eight proteins have not been identified in the
      group of controls and have been observed in a remarkable proportion of patients,
      mainly involved in immune system activity (CD177, Swiprosin-1 and 2-oxoglutarate
      dehydrogenase). Arylsulfatase has been identified in the group of controls and
      was absent in all patients with infection. Three proteins (TIMP-1, WFDC domain
      protein 2 and Carboxypeptidase E) have been observed significantly different in
      patients versus controls, mainly related with inflammation. CONCLUSIONS: This is
      the first application of MS-based proteomics aimed to reveal an array of proteins
      in the seminal plasma and reflecting the effect of the infection by E. faecalis
      on semen composition.

PMID- 29651939
TI  - Role of Sertoli Cell Proteins in Immunomodulation.
AB  - BACKGROUND: Sertoli cell, over the past 30 years, have been elevated from simple
      mechanical elements to the rank of a "sentinel" in spermatogenesis. By delivering
      potent immunomodulatory and trophic proteins, Sertoli cells are unique cell type
      with a pivotal role in maintaining testis immune privilege and the immune
      protection of the antigenic germ cells. CONCLUSIONS: The findings from SC
      transplantation studies utilizing experimental animal models of disease,
      demonstrate the presence of the same immuno-modulation properties and mechanisms
      at tissue and organ sites far from testis. The complex pathways that generate and
      maintain the immune tolerance involve the production of several immunomodulatory
      or immune-related proteins such as cytokines, chemokines, growth factors,
      mediators of the inflammation, complement inhibitors or adhesion molecules. A
      better definition and understanding of these Sertoli cell proteins and the
      mechanisms of immunoprotection should help to elucidate their role in the
      spermatogenic process. The demonstration of their capabilities in transplantation
      experiments suggests that Sertoli cells may be good candidates in cell therapy
      for a number of cell-mediated chronic diseases.

PMID- 29651940
TI  - Proteomics in Human Reproduction.
AB  - BACKGROUND: Assisted Reproduction Techniques (ART) have significantly advanced
      since the first successful In Vitro Fertilization (IVF). However, most in vitro
      produced embryos fail to implant. Key steps in ART are the correct infertility
      diagnosis, in order to manage the individualised treatments, and the assessment
      of gamete and embryo viability, to identify the embryo with the best implantation
      potential. OBJECTIVE: The goal for this manuscript was to present a brief review
      of proteomics in Assisted Reproduction Technologies (ART) and raises the question
      of whether proteomics is a good alternative for the future of ART. METHODS: A
      literature review concerning proteomics and assisted reproduction was conducted.
      RESULTS: Non-invasive approaches to correctly diagnose infertility and to access
      embryo development potential have the advantages of increasing our knowledge
      about embryo physiology, therefore allowing the development of methods to predict
      developmental competence and viability. These approaches include proteomic
      profiling and other omics technologies. CONCLUSION: The use of proteomics in
      clinical practice goes beyond the identification of the oocytes and embryos with
      the best developmental potentials, it may add to the diagnosis of both male and
      female infertility and in the future, it may be a laboratory tool that will
      contribute to the birth of a healthy child.

PMID- 29651941
TI  - Identification of Adjacent NNRTI Binding Pocket in Multi-mutated HIV1- RT Enzyme
      Model: An in silico Study.
AB  - INTRODUCTION: A possible strategy to combat mutant strains is to have a thorough
      structural evaluation before and after mutations to identify the diversity in the
      non-nucleoside inhibitor binding pocket and their effects on enzyme-ligand
      interactions to generate novel NNRTI's accordingly. OBJECTIVE: The primary
      objective of this study was to find effects of multiple point mutations on NNRTI
      binding pocket. This study included the contribution of each individual mutation
      in NNIBP that propose an adjacent binding pocket which can be used to discover
      novel NNRTI derivatives. METHODS: An in Silico model of HIV-1 RT enzyme with
      multiple mutations K103N, Y181C and Y188L was developed and evaluated. Two
      designed NNRTI pyridinone derivatives were selected as ligands for docking
      studies with the homology model through alignment based docking and residue based
      docking approaches. Binding pockets of wild type HIV-1 RT and multi-mutated
      homology model were compared thoroughly. RESULT AND DISCUSSION: K103N mutation
      narrowed the entrance of NNRTI binding pocket and forbade electrostatic
      interaction with alpha amino group of LYS103. Mutations Y181C and Y188L prevented
      NNRTI binding by eliminating aromatic pi interactions offered by tyrosine rings.
      Docking study against new homology model suggested an adjacent binding pocket
      with combination of residues in palm and connection domains. This pocket is
      approximately 14.46A away from conventional NNRTI binding site. CONCLUSION:
      Increased rigidity, steric hindrance and losses of important interactions
      cumulatively prompt ligands to adapt adjacent NNRTI binding pocket. The proposed
      new and adjacent binding pocket is identified by this study which can further be
      evaluated to generate novel derivatives.

PMID- 29651942
TI  - An Expedient Synthesis of CMF-019: (S)-5-Methyl-3-{1-(pentan-3-yl)-2- (thiophen-2
      ylmethyl)-1H-benzo[d]imidazole-5-carboxamido}hexanoic Acid, a Potent Apelin
      Receptor (APJ) Agonist.
AB  - BACKGROUND: Apelin receptor (APJ) is a G protein-coupled receptor (GPCR)
      activated by the endogenous peptide apelin. The apelin-APJ system has emerged as
      an important regulator of cardiovascular homeostasis. Recently, a potent
      benzimidazole-derived apelin peptidomimetic, CMF-019, was patented but without a
      comprehensive description of its synthesis and a complete spectroscopic
      characterization of the intermediates. OBJECTIVE: Here, a detailed preparation of
      CMF-019 through a modified and improved synthetic pathway is described. METHOD:
      In particular, the benzimidazole ring in 7 was tailored by the condensation of
      methyl 3- amino-4-(pentan-3-ylamino)benzoate (4) with (thiophene-2-yl)acetimidate
      salt 6. Saponification of 7 and the subsequent condensation of the free acid 8
      with the corresponding enantiopure beta-amino acid methyl ester generated methyl
      (S)-5-methyl-3-{1-(pentan-3-yl)-2-(thiophen-2-ylmethyl)-1Hbenzo[ d]imidazole-5
      carboxamido}hexanoate (9). Hydrolysis of the latter with KOH in THF/water,
      followed by HPLC-purification, afforded the desired product, CMF-019 (potassium
      salt) 10. RESULTS & CONCLUSION: The approach reported herein enables preparation
      of 10 at a total yield of 12% over seven linear steps. Additionally, it does not
      require applying expensive designated microwave reactors and high-pressure
      hydrogenators. Thus, the elaborate synthesis provides a latent availability of
      potent agonist 10 for further exploring the physiologically essential apelin-APJ
      system.

PMID- 29651943
TI  - Benzoin Schiff Bases: Design, Synthesis, and Biological Evaluation as Potential
      Antitumor Agents.
AB  - BACKGROUND: Phosphoinositide 3-kinase alpha (PI3Kalpha) is an attractive target
      for anticancer drug design. OBJECTIVES: Target compounds were designed to probe
      the significance of alcohol and imine moieties tailored on a benzoin scaffold to
      better understand the structure activity relation (SAR) and improve their
      biological activity as anticancer compounds. METHODS: Chemical synthesis of the
      targeted compounds, biological evaluation tests against human colon
      adenocarcinoma (HCT-116), breast adenocarcinoma (MCF-7), and breast carcinoma
      (T47D) cell lines, as well as Glide docking studies were employed in this
      investigation. RESULTS: A new series of 1,2-diphenylimino ethanol was
      successfully synthesized and characterized by means of FT-IR, HRMS, NMR, and by
      elemental analysis. Biological screening revealed that the newly synthesized
      compounds inhibit PI3Kalpha activity in human colon adenocarcinoma (HCT-116),
      breast adenocarcinoma (MCF-7), and breast carcinoma (T47D) cell lines. Results
      additionally showed that these compounds exhibit selective antiproliferative
      activity, induce apoptosis, and suppress the VEGF production. Compounds 2b, 2d,
      and 2g displayed promising inhibitory activity in HCT-116 suggesting that
      hydrophobic and/or hydrogen bond-acceptor mediate(s) ligand-receptor interaction
      on o- and mpositions. Furthermore, compounds 2g, 2i, 2j, and 2h, bearing
      hydrophobic moiety on m- and pposition, exerted high antiproliferative activity
      in T47D and MCF-7 cells, whereas compound 2e showed selectivity against T47D and
      MCF-7. Molecular docking studies against PI3Kalpha and caspase-3 demonstrated a
      strong correlation between the predicted binding affinity (DeltaGobsd) and IC50
      values of prepared compounds for the caspase-3 model, implying that the cellulous
      inhibitory activity was caspase-3-dependent. Moreover, Glide docking against
      PI3Kalpha identified Ser774, Lys802, E849, V851, and Asp933 as key binding
      residues. CONCLUSION: The series exerted a potential PI3Kalpha inhibitory
      activity in human carcinoma cell lines expressing PI3Kalpha.

PMID- 29651944
TI  - Role of Point-of-Care Ultrasonography for the Management of Sepsis and Septic
      Shock.
AB  - BACKGROUND: Sepsis and septic shock remain a major cause of morbidity and
      mortality globally. In recent years, the outcome of patients with sepsis and
      septic shock has gradually improved, in part due to early recognition and timely
      appropriate management. Bedside physical examination can be of limited value to
      identify the source of infection and to decide appropriate management. Moreover,
      the clinical status of these patients can change rapidly, as a part of disease
      progression or in response to treatment or intervention. METHODS: Research
      articles, review papers and online contents related to point-of-care ultrasound
      for the management of patients with sepsis and septic shock were reviewed.
      RESULTS: Point-of-care ultrasonography can be a valuable bedside tool to rapidly
      identify the potential source of infection and associated organ dysfunction. It
      can also help to guide management to predict fluid responsiveness by assessing
      the variation of inferior venacava with respiration, ventricular size and aortic
      flow variation. Response to various interventions like a fluid challenge or
      administration of inotropes can be assessed at the bedside. Point-of-care
      ultrasound can also enhance safety and increase the success of bedside procedures
      like central venous cannulation and drainage of pleural effusion. CONCLUSION:
      Bedside ultrasound can help to individualize management of patients with sepsis
      and septic shock and may potentially improve patient outcome.

PMID- 29651945
TI  - Modeling of a Cyclotron Target for the Production of 11C with Geant4.
AB  - BACKGROUND: In medical cyclotron facilities, 11C is produced according to the
      14N(p,alpha)11C reaction and widely employed in studies of prostate and brain
      cancers by Positron Emission Tomography. It is known from literature that the 11C
      target assembly shows a reduction in efficiency during time, meaning a decrease
      of activity produced at the end of bombardment. This effect might depend on
      aspects which are still not completely known. OBJECTIVE: Possible causes of the
      loss of performance of the 11C-target assembly were addressed by Monte Carlo
      simulations. METHODS: Geant4 was used to model the 11C-target assembly of a GE
      PETtrace cyclotron. The physical and transport parameters to be used in the
      energy range of medical applications were extracted from literature data and 11C
      routine productions. The Monte Carlo assessment of 11C saturation yield was
      performed varying several parameters such as the proton energy and the angle of
      the target assembly with respect to the proton beam. RESULTS: The estimated 11C
      saturation yield is in agreement with IAEA data at the energy of interest, while
      it is about 35% greater than the experimental value. A more comprehensive
      modeling of the target system, including thermodynamic effect, is required. The
      energy absorbed in the inner layer of the target chamber was up to 46.5 J/mm2
      under typical irradiation conditions. CONCLUSION: This study shows that Geant4 is
      potentially a useful tool to design and optimize targetry for PET radionuclide
      productions. Tests to choose the Geant4 physics libraries should be performed
      before using this tool with different energies and materials.

PMID- 29651946
TI  - Neoadjuvant Therapy Is Essential for Resectable Pancreatic Cancer.
AB  - BACKGROUND: Awareness of the benefits of neoadjuvant therapy is increasing, but
      its use as an initial therapeutic option for patients with resectable pancreatic
      cancer remains controversial, especially for those patients without high-risk
      prognostic features. Even for patients with high-risk features who are candidates
      to receive neoadjuvant therapy, no standard regimen exists. METHODS: In this
      review, we examined available data on neoadjuvant therapy in patients with
      resectable pancreatic cancer, including prospective studies, retrospective
      studies, and ongoing clinical trials, by searching PubMed/MEDLINE,
      ClinicalTrials.gov, Web of Science, and Cochrane Library. The characteristics and
      results of screened studies were described. RESULTS: Retrospective and
      prospective studies with reported results and ongoing randomized studies were
      included. For patients with resectable pancreatic cancer, neoadjuvant therapy
      provides benefits such as increased survival, decreased risk of comorbidities and
      mortality, and improved cost-effectiveness due to increased completion rate of
      multimodal treatment. Highly active regimens such as FOLFIRINOX (folinic acid,
      fluorouracil, irinotecan, and oxaliplatin) or gemcitabine plus nab-paclitaxel are
      considered acceptable therapeutic regimens. Additionally, platinum-containing
      regimens other than FOLFIRINOX are acceptable for select patients. Other
      therapies, such as chemoradiation treatment, immuno-oncology agents, and targeted
      therapies are being explored and the results are highly anticipated. CONCLUSION:
      This review highlights the benefits of neoadjuvant therapy for resectable
      pancreatic cancer. Some regimens are currently acceptable, but need more evidence
      from well-designed clinical trials or should be used on after being carefully
      examined by a multidisciplinary team.

PMID- 29651947
TI  - Transplantation of BDNF Gene Recombinant Mesenchymal Stem Cells and Adhesive
      Peptide-modified Hydrogel Scaffold for Spinal Cord Repair.
AB  - INTRODUCTION: Mesenchymal Stem Cells (MSCs) are promising candidates for nerve
      tissue engineering. Brain Derived Neurotrophic Factor (BDNF) secreted by MSCs can
      function to increase neural differentiation and relieve inflammation response.
      Gene transfection technology is an efficient strategy to increase the secretion
      levels of cytokines and enhance cellular functions. However, transfection and in
      vivo gene expression of environmentally sensitive stem cells have been one of the
      most challenging subjects due to the requirement in both safety and transfection
      efficiency. In this study, gene transfection technology was applied to prepare
      BDNF gene recombinant MSCs based on our previously reported liposomal vector
      ScreenFect(r) A. To improve cellular survival and gene expression after in situ
      implantation of MSCs, an adhesive peptide modified hydrogel scaffold was
      constructed using hyaluronic acid. The scaffold was optimized and modified with
      an adhesive peptide PPFLMLLKGSTR. The transfected MSCs exhibited improved
      cellular survival and sustained gene expression in the three-Dimentional (3D)
      scaffold in vitro. Compared to untransfected MSCs, gene recombinant MSCs
      effectively improved spinal tissue integrity, inhibited glial scar formation and
      alleviated inflammatory response. These effects were found discounted when cells
      were implanted without the scaffold. CONCLUSION: The study developed a promising
      implantation system for therapy of severe spinal cord injury and provided the
      first understanding of Screenfect(r) A about its functions on stem cell therapy
      for nerve tissue repair as well as three-dimentional gene expression.

PMID- 29651948
TI  - Therapeutic potential of multifunctional tacrine analogues.
AB  - Tacrine is a potent inhibitor of cholinesterases (acetylcholinesterase and
      butyrylcholinesterase) that shows limiting clinical application by liver
      toxicity. In spite of this, analogues of tacrine are considered as model
      inhibitor of cholinesterases in the therapy of Alzheimer's disease. The interest
      in these compounds is mainly related to a high variety of their structure and
      biological properties. In the present review, we have described the role of
      cholinergic transmission and treatment strategies in Alzheimer's disease as well
      as the synthesis and biological activity of several recently developed classes of
      multifunctional tacrine analogues and hybrids, which consist a new paradigm to
      treat Alzheimer's disease. We have also reported potential of these analogues in
      the treatment of Alzheimer's diseases in various experimental systems.

PMID- 29651949
TI  - Nerve Growth Factor: Early Studies and Recent Clinical Trials.
AB  - Since its discovery, nerve growth factor (NGF) has long occupied a critical role
      in developmental and adult neurobiology for its many important regulatory
      functions on the survival, growth and differentiation of nerve cells in the
      peripheral and central nervous system. NGF is the first discovered member of a
      family of neurotrophic factors, collectively indicated as neurotrophins, (which
      include brain-derived neurotrophic factor, neurotrophin-3 and neurotrophin 4/5).
      NGF was discovered for its action on the survival and differentiation of selected
      populations of peripheral neurons. Since then, an enormous number of basic and
      human studies were undertaken to explore the role of purified NGF to prevent the
      death of NGF-receptive cells. These studies revealed that NGF possesses important
      therapeutic properties, after topical administration, on human cutaneous pressure
      ulcer, corneal ulcers, glaucoma, retinal maculopathy, Retinitis Pigmentosa and in
      pediatric optic gliomas and brain traumas. The aim of this review is to present
      our previous, recent and ongoing clinical studies on the therapeutic properties
      of NGF.

PMID- 29651950
TI  - Roles of TRAF6 in Central Nervous System.
AB  - Tumor necrosis factor receptor-associated factor (TRAF) is an important binding
      protein of tumor necrosis factor (TNF) superfamily and the toll/IL-1 receptor
      (TIR) superfamily, which play an important role in innate immunity and acquired
      immunity. TRAFs family have 7 members (TRAF1-7), and TRAF6 has its special
      facture and biological function. TRAF6 has two special domains: C-terminal domain
      and N-terminal domain, which could integrate with multiple kinases and regulate
      signaling pathway function as an E3 ubiquitin ligase. Studies have increasingly
      found that TRAF6 is closely related to central nervous system diseases, such as
      stroke, Traumatic brain injury, neurodegenerative diseases and neuropathic pain.
      Further research on the pathophysiological mechanism may be expected to become
      the new targets for the treatment of central nervous system diseases.

PMID- 29651951
TI  - Inflammatory Events Following Subarachnoid Hemorrhage (SAH).
AB  - Acute SAH from a ruptured intracranial aneurysm contributes for 30% of all
      hemorrhagic strokes. The bleeding itself occurs in the subarachnoid space.
      Nevertheless, injury to the brain parenchyma occurs as a consequence of the
      bleeding, directly, via several well-defined mechanisms and pathways, but also
      indirectly, or secondarily. This secondary brain injury following SAH has a
      variety of causes and possible mechanisms. Amongst others, inflammatory events
      have been shown to occur in parallel to, contribute to, or even to initiate
      programmed cell death (PCD) within the central nervous system (CNS) in human and
      animal studies alike. Mechanisms of secondary brain injury are of utmost interest
      not only to scientists, but also to clinicians, as they often provide
      possibilities for translational approaches as well as distinct time windows for
      tailored treatment options. In this article, we review secondary brain injury due
      to inflammatory changes, that occur on cellular, as well as on molecular level in
      the various different compartments of the CNS: the brain vessels, the
      subarachnoid space, and the brain parenchyma itself and hypothesize about
      possible signaling mechanisms between these compartments.

PMID- 29651952
TI  - Special Traumatized Populations: Accidental Hypothermia in Children.
AB  - Physicians caring for children in trauma settings must consider and treat
      hypothermia as a cause for morbidity and mortality. Knowledge of treatment of
      accidental hypothermia with and without an asphyxial event is paramount.
      Clinicians need to identify hypothermia immediately and be aware of the overall
      management utilizing aggressive rewarming and cardiopulmonary resuscitation to
      help improve the survival of these critically ill children. This section reviews
      the epidemiology, clinical effects, and management options for accidental
      hypothermia in children.

PMID- 29651953
TI  - Comparison Between Supervised and Partly Supervised Cardiac Rehabilitation
      Protocols in Hypertensive Patients: A Randomized Controlled Trial.
AB  - BACKGROUND: Hypertension (HTN) is the main cause of cardiovascular diseases
      accounting for one-third of global mortality. Physical exercise reduces the
      incidence and prevalence of HTN and cardiovascular morbidity and mortality.
      Exercises recommended for hypertensive patients include supervised cardiac
      rehabilitation, which occurs in rehabilitation centers, and partly supervised
      rehabilitation, with the individual prescription of exercises conducted at
      patients' residences. OBJECTIVE: Compare clinical and functional parameters of
      hypertensive patients subjected to two cardiac rehabilitation protocols:
      supervised and partly supervised. METHOD: Hypertensive patients stage I or II
      were randomly divided into group one (G1) (partly supervised cardiac
      rehabilitation) and group two (G2) (supervised cardiac rehabilitation). All
      patients performed a warm-up, aerobic exercise, strength training and cool-down.
      Participants' assessments conducted before and after intervention included:
      physical examination, six-minute walk test, cardiac stress test, metabolic tests,
      and central and peripheral blood pressure measurements. RESULTS: A total of 61
      patients (mean age 60.3+/-11.3 years, 78.7% women) were randomized (30 in G1 and
      31 in G2). At the end of the intervention, G1 increased 30.6 meters (p=0.004) and
      G2 increased 55.0 meters (p>0.001) the distance covered in the six-minute walk
      test. G2 showed an increase in the maximum oxygen consumption from 24.7+/-8.6
      mlO2/Kg/min to 28.4+/-7.5 mlO2/Kg/min (p=0.003). Compliance with the intervention
      was similar in G1 and G2 (77.5+/-11% x 82+/-10%; p=0.654). CONCLUSION:
      Participants from both groups improved their physical fitness and showed
      satisfactory compliance and tolerability to the interventions. The supervised
      exercise was more effective in improving muscle strength and some physical
      fitness parameters.

PMID- 29651954
TI  - Forward and Backward Aortic Components and Reflection Indexes in Children and
      Adolescents: Determinants and Role in High Pressure States.
AB  - BACKGROUND: High blood pressure states (HBP) would differ in wave components and
      reflections indexes, which could associate clinical and prognostic implications.
      The study aims: 1) to characterize the association of aortic wave components and
      reflection parameters (backward [Pb], forward [Pf], Pb/Pf ratio and augmentation
      index [AIx]) with demographic, anthropometric, hemodynamic and arterial
      parameters in healthy children and adolescents; 2) to generate multivariate
      prediction models for the associations, to contribute to understand the main
      determinants of Pf, Pb, Pb/Pf and AIx; 3) to identify if differences in wave
      reflection indexes observed in HBP could be explained by differences in the
      analyzed parameters. METHODS: Healthy children and adolescents (n=816, females:
      386; Age: 3-20 years) were studied. EVALUATIONS: central aortic pressure and wave
      components (Pb, Pf, Pb/Pf and AIx determination with SphygmoCor [SCOR] and Mobil
      o-Graph [MOG]); anthropometric assessment; regional arterial stiffness (carotid
      femoral, carotid-radial pulse wave velocity [PWV] and PWV ratio); carotid intima
      media thickness; carotid and femoral distensbility; cardiac output; systemic
      vascular resistances (SVR). Simple and multiple regression models were
      constructed to determine aortic wave parameters; the main explanatory variables.
      Normotensive and HBP groups were compared. Differences in wave reflection indexes
      were analyzed before and after controlling for explanatory variables.
      Equivalences between SphygmoCor and Mobil-O-Graph data were assessed (correlation
      and Bland-Altman analyses). RESULTS AND CONCLUSION: There were systematic and
      proportional differences between the data obtained with SphygmoCor and Mobil-O
      Graph devices. Heart rate (HR), peripheral pulse pressure, height and weight were
      the variables that isolated (simple associations) or combined (multiple
      associations), showed the major capability to explain interindividual differences
      in Pf, Pb, Pb/Pf and AIx. Arterial stiffness also showed explanatory capacity,
      being the carotid the artery with the major contribution. HBP associated higher
      Pf, Pb, AIx and lower Pb/Pf ratio. Those findings were observed together with
      higher weight, arterial stiffness and HR. After adjusting for anthropometric
      characteristics, HR, cardiac output and SVR, the HBP group showed greater Pf and
      Pb. Then, Pf and Pb characteristics associated with HBP would not be explained by
      anthropometric or hemodynamic factors. Evaluating wave components and reflection
      parameters could contribute to improve the comprehension and management of HBP
      states.

PMID- 29651955
TI  - Increases in Peripheral Systolic Pressure Levels and Z-score Associate Gradual
      Aortic Pressure Increase and Functional Arterial Impairment in Children and
      Adolescents.
AB  - BACKGROUND: Arterial changes associated with children and adolescents high blood
      pressure (HBP) states would vary depending on the arterial type, arterial indexes
      considered and/or on blood pressure (BP) levels. AIMS: To determine in children
      and adolescents: 1) if there is gradual structural-functional arterial impairment
      associated with gradual peripheral (brachial) systolic BP (pSBP) level or z-score
      increases, and 2) whether subjects with HBP levels and those with normal BP
      differ in the profiles of arterial changes associated with pSBP deviations.
      METHODS: 1005 asymptomatic children and adolescents were included. Clinical,
      anthropometric and arterial non-invasive evaluations were performed. Heart rate,
      brachial BP, aortic BP and wavederived parameters (i.e. augmentation index),
      carotid and femoral diameters, blood velocities and elastic modulus, carotid
      intima-media thickness and aortic pulse wave velocity, were obtained. Two groups
      were assembled: Reference (without cardiovascular risk factors (CVRFs); n=379)
      and HBP (n=175). Additionally, subjects were ascribed to groups according to
      their pSBP z-scores (z-score <= 0, 0< z-score < 1 or z-score >= 1). Age and sex
      related mean and standard deviation equations were obtained for each variable
      (Reference group). Using those equations, data (entire population) were converted
      into z-scores. Groups were compared (absolute and z-scored variables) before and
      after adjusting for cofactors (ANOVA/ANCOVA). Linear regression analyses were
      done considering: pSBP and z-pSBP (independent) and absolute levels and z-scores
      for hemodynamic and arterial indexes (dependent variables). Differences in
      hemodynamic and arterial levels and z-scores variations (dependent) associated
      with variations in pSBP and z-pSBP (independent variable) were assessed. The
      slopes of the models for Reference and HBP groups were compared. CONCLUSION: HBP
      states associate hemodynamic and arterial changes not explained by exposure to
      other CVRFs, anthropometric or demographic factors. The higher the pSBP
      deviations from ageand sex-expected mean value in the Reference group, the higher
      the hemodynamic and arterial indexes deviation. The pSBP-related variations in
      hemodynamic and arterial indexes would not differ depending on whether HBP states
      are present or not.

PMID- 29651956
TI  - Quantitative Vascular Evaluation: From Laboratory Experiments to Point-of-Care
      Patient (Clinical Approach).
AB  - To enhance the efficiency of patient-specific risk stratification and diagnosis,
      an assessment of arterial structural and functional changes associated to a
      vascular disease in both early and advanced stages have been proposed, with the
      objective of limiting the progression or revert vascular alterations. In this
      connection, an interdisciplinary international partnership made up by research
      institutions from France, Argentina, Uruguay and Spain was established, with the
      objective of contributing to the evaluation and follow-up of factors involved in
      the physiopathology of cardiometabolic diseases and human aging. Several studies,
      such as the effect of hypertension in large arteries, alterations in arterial
      wall viscosity, stiffness and inertia, endothelial function and vascular
      reactivity, cardiovascular risk improvement, vascular age assessment and
      cryografts vascular response evaluation were carried out as a result of this
      international collaboration during the last twenty-five years.

PMID- 29651957
TI  - Serum Uric Acid Elevation is Associated to Arterial Stiffness in Hypertensive
      Patients with Metabolic Disturbances.
AB  - INTRODUCTION: Chronic serum uric acid elevation (SUA) is known to be induced by
      dyslipidemia, hypertension, inflammation, and insulin resistance. Therefore, it
      has been associated with higher risk for coronary artery disease and
      cardiovascular mortality. Also, increased levels of SUA have been associated with
      regional arterial stiffness, assessed by pulse wave velocity (PWV). AIMS: To
      evaluate the relationships of PWV, SUA and different metabolic parameters in
      essential hypertensive patients. MATERIAL AND METHODS: We evaluated 445 essential
      hypertensive patients, by measuring office blood pressure (BP), weight, height,
      and waist circumference. In each patient, blood samples were drawn for
      biochemical evaluations and 24h urine collection. Body Mass Index (BMI) and
      Glomerular Filtration Rate (GFR) were calculated. Carotid-Femoral PWV and Left
      Ventricular Mass Index (LVMI) were measured in all patients. RESULTS: All
      subjects (n=402), 242 males (55+/-0.9 yrs.; BMI: 28.9+/-0.3 Kg/m2) and 160
      females (58+/-1 yrs.; BMI: 28.1+/-0.4 Kg/m2) had normal renal function. PWV
      values showed a significant association with SUA (p<0.001), Systolic BP (p<0.025)
      and LVMI (p<0.05). SUA showed a significant association, p<0.025: with BMI, Waist
      Circumference, and HDL-C; p<0.05: with Glycaemia at 120 min, Insulin at 120 min,
      TG, and LVMI; and p<0.001: with serum Creatinine. Backward Stepwise Regression
      showed that PWV could be predicted from SUA (p<0.001) and Systolic BP (p<0.05).
      BMI, Waist Circumference, DBP and HR did not significantly add to the ability of
      the equation to predict PWV. CONCLUSIONS: In this population of essential
      hypertensive patients, SUA was associated to increased arterial stiffness and to
      components of the Metabolic Syndrome. These results raise the possibility that a
      new approach to the role of SUA, linked to cardiovascular stratification, and a
      most appropriate treatment might be considered.

PMID- 29651958
TI  - Arterial Stiffness in Haemodialyzed Patients: Findings and Controversies.
AB  - Vascular research in end-stage renal diseases is an interesting field in which
      the characterization of arterial stiffness proved to be valuable to predict
      morbidity and mortality. Particularly, patients on renal replacement therapy have
      been reported to have significant increases in arterial stiffness and
      cardiovascular mortality. The clinical relevance of the measurement of arterial
      stiffness is linked to therapeutical and preventive interventions. The purpose of
      this work is to analyze the results of the scientific research in the field of
      arterial stiffness, in which hemodialyzed patients were involved, emphasizing on
      clinical and in-vitro research carried out by our group compared to contributions
      previously reported in the specialized literature. These investigations are
      necessary to improve diagnostic strategies and monitor the arterial response to
      therapeutical interventions in chronic kidney disease.

PMID- 29651959
TI  - Central-To-Peripheral Arterial Stiffness Gradient in Hemodialyzed Patients
      Depends on the Location of the Upper-limb Vascular Access.
AB  - BACKGROUND: Pulse wave velocity ratio (PWV-ratio), a measure of central-to
      peripheral arterial stiffness gradient, is calculated as a quotient between
      carotid-femoral and carotid-radial PWV (cf-PWV/cr-PWV). This new index has been
      reported to be significantly associated with increased mortality in hemodialyzed
      patients. Since several reports showed differences in arterial stiffness
      regarding the pathway where the vascular access (VA) is, the purpose of this
      research was: a) to compare arterial stiffness values obtained in the left and
      right sides of the body in hemodialyzed and non-hemodialyzed patients, and b) to
      analyze PWV-ratio values obtained on the side of the body where the VA was placed
      and compare them to its contralateral intact side. Since it is difficult to
      adequately measure cr-PWV in patients with a VA in the forearm, we measured the
      carotid- brachial PWV (cb-PWV) and used it to calculate PWV-ratio (cf-PWV/cb
      PWV). METHODS: A Pearson's correlation and Bland & Altman analysis were performed
      in hemodialyzed (n=135) and non-hemodialyzed (n=77) patients, to quantify the
      equivalence between arterial stiffness parameters (cf-PWV, cb-PWV, PWV-ratio)
      obtained on each side of the body with respect to its contralateral side.
      RESULTS: We conclude that PWV-ratio values measured on the side where the VA is
      placed were significantly higher than those obtained in its contralateral side,
      in hemodialyzed patients included in this research. Moreover, cf-PWV, cb-PWV and
      PWV-ratio values obtained on one side of the body were always highly correlated
      with its contralateral side. CONCLUSION: According to this research, any research
      involving PWV-ratio should always consider the observed territory.

PMID- 29651960
TI  - Targeting Brain Tumors with Nanomedicines: Overcoming Blood Brain Barrier
      Challenges.
AB  - BACKGROUND: This review elucidates ongoing research, which show improved delivery
      of anticancer drugs alone and/ or enclosed in carriers collectively called
      nanomedicines to cross the BBB/ BTB to kill tumor cells and impact patient
      survival. We highlighted various advances in understanding the mechanism of BTB
      function that has an impact on anticancer therapeutics delivery. We discussed
      latest breakthroughs in developing pharmaceutical strategies, including
      nanomedicines and delivering them across BTB for brain tumor management and
      treatment. METHODS: We performed an extensive literature search and highlighted
      important studies on the regulation of BTB permeability with respect to nanotech
      based nanomedicines for targeted treatment of brain tumors. We have reviewed
      research articles that describe the development of specialized molecules and
      nanospheres, which carry payload of anticancer agents to brain tumor cells across
      the BBB/ BTB and avoid drug efflux systems. We highlighted research on the
      identification and development of targeted anti-cancer drug delivery to brain
      tumors. In addition, we discussed multimeric molecular therapeutics and
      nanomedicines that were encapsulated in nanospheres for treatment and monitoring
      of brain tumors. RESULTS: In this context, we quoted our research on large
      conductance calcium-activated potassium channels (BKCa) and ATP-dependent
      potassium channels (KATP) as portals of enhanced antineoplastic drugs delivery.
      We showed that several innovative drug delivery agents such as liposomes,
      polymeric nanoparticles, dendrimers and many such tools can be utilized to
      improve anticancer drugs and nanomedicines across the BTB to reach brain tumor
      cells. CONCLUSION: This review might interest both academic and drug company
      scientists involved in drug delivery to brain tumors. We further seek to present
      evidence that BTB modulators can be clinically developed as combination drug or/
      and as stand-alone anticancer drugs. Eventually, it is expected that unrelenting
      effort from the scientific community in developing novel drug delivery methods
      should increase the survival rate of brain tumor patients, which is dismally low
      presently.

PMID- 29651961
TI  - The Benefit of Prescribing Vitamin D as Add on Therapy on the
      Electrocardiographic Changes in Epileptic Patients.
AB  - BACKGROUND: Epileptic children and adolescent have a significantly low serum
      level of vitamin D due to the effect of antiepileptic drugs on the vitamin D
      metabolism. Those patients are at risk of cardiovascular events. OBJECTIVE: This
      study aimed to show that epileptic patients who treated with antiepileptic drugs
      supplemented with vitamin D are free from the electrocardiograph changes compared
      with those treated with antiepileptic drugs. METHOD: This cross-sectional study
      included, 121 epileptic patients aged < 18 years of both genders with a history
      of idiopathic generalized tonic clonic seizure. They grouped into Group I (n=20)
      patients without medical treatment, Group II (n=76) patients treated with
      antiepileptic drugs, and vitamin D Group III (n=25) patients treated with
      antiepileptic drugs supplemented with vitamin D3 vitamin D. Each participant
      subjected to the electrocardiogram investigation at the time of entry into the
      study. RESULTS: Group III patients had a significant decrease of QRS complex, QRS
      dispersion QTcorrected, and TQ duration compared with Group II. Group I patients,
      had a significant increase of QRS complex duration, compared with Group II
      patients. Four patients of Group II showed a significant prolonged QT-interval in
      the QT nomogram. Three patients had a JT index (an indicator of ventricular
      hyperpolarization) more than the normal cutoff level of 112. The area under the
      curve of receiving operating characteristics showed significant favorable effects
      of vitamin D supplementation on the different variables of electrocardiograph.
      CONCLUSION: Vitamin D supplementation may correct the changes in the
      electrocardiograph observed in idiopathic generalized tonic clonic seizure
      treated with antiepileptic medicines, and our observations warrant larger
      studies.

PMID- 29651962
TI  - Phase IV Studies: Some Insights, Clarifications, and Issues.
AB  - BACKGROUND: There is an increasing need to face regulatory aspects as well as
      ethics and scientific ones in the pharmaceutical research phase after the
      authorization of a drug. Traditionally, Phase IV studies, after the authorization
      of a drug to be marketed by the Competent Authority like the Food and Drug
      Administration (FDA) (in Europe, European Medicine Agency - EMA- through National
      Procedures or Community Procedures) have been considered mainly aimed to the
      assessment of the new drug safety profile. However, the sample size calculation
      for such aim is still an open issue. Moreover, the benefit/risk assessment is a
      compelling global need. METHODS: This editorial aims to give a fairly exhaustive
      overview of the main topics currently present in the pharmaceutical research
      phase after the authorization of a drug. FDA and EMA guidelines are considered
      under a comparative perspective with a focus on the perspective of "Post
      Authorization Safety Studies (PASS)" and "Post Authorization Efficacy Studies
      (PAES)" with critical considerations. Then, the approach of "Explanatory Trials"
      and "Pragmatic Trials" is proposed under the horizon of Health Technology
      Assessment (HTA). CONCLUSION: Critical remarks are raised against the pure
      commercial perspective in the proposal of PASS and PAES and on the design of
      registries which should be planned with relevant objectives to be pursued by
      appropriate statistical analyses reported in the Statistical Analysis Plan (SAP)
      of the study protocol. Finally, a particular focus is placed on the work of the
      Ethical Committees regarding the approval of the observational studies on the
      safety and the efficacy of the drugs in their pragmatic clinical use.

PMID- 29651963
TI  - Physicochemical characterization of curcumin loaded chitosan nanoparticles:
      Implications in cervical cancer.
AB  - Curcumin is a potent anticancer agent and has great potential efficacy against
      different types of cancers. A major disadvantage of curcumin, however, is its
      poor solubility and bioavailability. The aim of the present work is to synthesize
      chitosan and curcumin-loaded chitosan nanoparticles and their characterization
      through various physicochemical methods and cellular uptake in cervical cancer
      cell line SiHa. The studies presented demonstrate that curcumin-loaded chitosan
      nanoparticles showed increased uptake in the SiHa cells as compared to free
      curcumin and chitosan nanoparticles did not show any significant uptake in SiHa
      cell line. The curcumin-loaded chitosan nanoparticles released more lactate and
      lower ATP as compared to native curcumin in cervical cancer lines such as SiHa,
      CaSki and HeLa. Thus, chitosan based curcumin nanoparticles could be used as a
      potent vector / delivery agent for drug targeting in the treatment of cervical
      cancer.

PMID- 29651964
TI  - Poly-L-arginine: Enhancing Cytotoxicity and Cellular Uptake of Doxorubicin and
      Necrotic Cell Death.
AB  - OBJECTIVE: Cell resistance to doxorubicin and its toxicity to healthy tissue
      reduce its efficiency. The use of cell penetrating peptides as drug delivery
      system along with doxorubicin is a strategy to reduce its side effects. In this
      study, the influence of poly-L-arginine on doxorubicin cytotoxicity, its cellular
      uptake and doxorubicin-induced apoptosis on human prostate cancer DU145 cells are
      assessed. METHODS: The cytotoxicity of doxorubicin and poly-L-arginine, alone and
      in combination, in DU145 cells was evaluated at different exposure times using
      MTT assay. The influence of poly-L-arginine on doxorubicin delivery into cells
      was evaluated by fluorescence microscopy and ultraviolet spectroscopy. DAPI and
      ethidium bromide-acridine orange stainings, flow cytometry using annexin
      V/propidium iodide, western blot analysis with anti-p21 antibody and caspase-3
      activity were used to examine the influence of poly-L-arginine on doxorubicin
      induced cell death. RESULTS: Poly-L-arginine had no cytotoxicity at low
      concentrations and short exposure times. Poly-L-arginine increased the cytotoxic
      effect of doxorubicin in DU145 cells in a time-dependent manner. But no
      significant reduction was found in HFF cell viability. Poly-L-arginine seems to
      facilitate doxorubicin uptake and increase its intracellular concentration. 24 h
      combined treatment of cells with doxorubicin (0.5 MUM) and poly-L-arginine (1 MUg
      ml-1) caused a small increase in doxorubicin-induced apoptosis and significant
      elevated necrosis in DU145 cells as compared to each agent alone. Conlusion: Our
      results indicate that poly-L-arginine at lowest and highest concentrations act as
      proliferation-inducing and antiproliferative agents, respectively. Between these
      concentrations, poly-L-arginine increases the cellular uptake of doxorubicin and
      its cytotoxicity through induction of necrosis.

PMID- 29651965
TI  - Antitumor Effect Of Pomolic Acid In Acute Myeloid Leukemia Cells Involves Cell
      Death, Decreased Cell Growth And Topoisomerases Inhibition.
AB  - BACKGROUND: Acute myeloid leukemia (AML) represent the largest number of annual
      deaths from hematologic malignancy. In the United-States, it is estimated that
      21.380 individuals will be diagnosed with AML and 49.5% of patients will die in
      2017. Therefore, the searching for novel compounds capable of increasing the
      overall survival rate to the treatment of AML cells is urgent. OBJECTIVES: To
      investigate the cytotoxicity effect of the natural compound PA and to explore the
      mechanism of action of PA in AML cell lines with different phenotypes. METHODS:
      It was used three different AML cell lines, HL60, U937 and Kasumi-1 cells with
      different mechanisms of resistance to analyze the effect of PA on the cell cycle
      progression, on DNA intercalation and on human DNA topoisomerases (hTopo I and
      IIalpha) in vitro studies. Theoretical experiments of the inhibition of hTopo I
      and IIalpha were done to explore the binding modes of PA. RESULTS: PA reduced
      cell viability, induced cell death, increased sub-G0/G1 accumulation and
      activated caspases pathway in all cell lines, altered the cell cycle distribution
      and inhibited the catalytic activity of both human DNA topoisomerases.
      CONCLUSION: Finally, this study showed that PA has powerful antitumor activity
      against AML cells suggesting that this natural compound might be a potent
      antineoplastic agent to improve the treatment scheme of this neoplasm.

PMID- 29651966
TI  - Specific cytostatic and cytotoxic effect of dihydrochelerythrine in glioblastoma
      cells: role of NF-kB/b-catenin and STAT3/IL-6 pathways.
AB  - : A glioblastoma is a primary CNS tumor that is more aggressive and lethal than
      other brain tumors. Its location, rapid proliferation, invasive growth,
      angiogenesis and immunosuppression are the main factors that limit its treatment,
      making it a major challenge to neuro-oncology. OBJECTIVE: This study investigated
      the in vitro effects of the alkaloid dihydrochelerythrine (DHC), which is
      extracted from Zanthoxylum stelligerum, on the viability, proliferation, cell
      death and b-catenin, NFkB, STAT3/pSTAT3 and interleukins roles. METHOD: In vitro
      experimental models of human (U251 and GL-15) and murine (C6) glioblastoma cells
      were cultured in the presence of DHC at increasing concentrations for MTT assay
      and exclusion trypan blue dye to determine EC50. Afterwards, C6 and U251 cells
      were treated with 100 MUM DHC or DMSO 0.1% for cell cycle, annexin and expression
      of b-catenin/NFkB/STAT3/pSTAT3 by flow cytometry or immunofluorescence.
      Interleukin quantification was made by Cytometric Bead Array. RESULTS: A
      significant decrease was observed in C6 and U251 cell viability in a time and
      dose-dependent manner. GL-15 cell viability decreased only when treated with 200
      MUM DHC. This maximum concentration affected neither astrocytes nor microglia
      viability. A cytostatic effect of DHC was observed in C6 and U251 cells after 48
      h of 100 mM DHC treatment. After 72 h of DHC treatment, C6 presented 80% of
      annexin-V+ cells compared to 10% of annexin-V+ U251 cells. C6 cells demonstrated
      significant high levels of NFk B and b-catenin cytoplasmic fraction.
      Additionally, DHC treatment resulted in higher significant levels of IL-6 than
      did other interleukins and STAT3 up regulation in U251 cells. CONCLUSION: These
      results demonstrate that DHC acts as a chemosensitizing agent selective for
      glioma cells not affecting non-tumor cells. Considering tumor heterogeneity, DHC
      demonstrated an anti-cancer potential to activate different cell death pathways.
      DHC demonstrated could be used for chemotherapy and immunotherapy applications in
      glioblastomas in the future.

PMID- 29651967
TI  - Design, synthesis, in vitro anti-cancer activity, ADMET profile and molecular
      docking of novel triazolo[3,4-a]phthalazine derivatives targeting VEGFR-2 enzyme.
AB  - In view of their expected anticancer activity, novel triazolo[3,4-a]phthalazine
      derivatives 5-6a-o and 3-substituted-bis([1,2,4]triazolo)[3,4-a:4&#039;,3&#039;
      c]phthalazines 9a-b were designed, synthesized and evaluated for their anti
      proliferative activity against two human tumor cell lines HCT-116 human colon
      adenocarcinoma and MCF-7 breast cancer. It was found that, compound 6o the most
      potent derivative against both HCT116 and MCF-7 cancer cell lines. Compounds 6o,
      6m, 6d and 9b showed the highest anticancer activities against HCT116 human colon
      adenocarcinoma with IC50 of 7+/-0.06, 13+/-0.11, 15+/-0.14 and 23+/-0.22 uM
      respectively while compounds 6o, 6d, 6a and 6n showed the highest anticancer
      activities against MCF-7 breast cancer with IC50 of 16.98+/-0.15, 18.2+/-0.17,
      57.54+/-0.53 and 66.45+/-0.67 uM respectively. Sorafenib as a highly potent VEGFR
      2 inhibitor was used as a reference drug with IC50 of 5.47+/-0.3 and 7.26+/-0.3
      uM respectively. Nine compounds were further evaluated for their VEGFR-2
      inhibitory activity. Compounds 6o, 6m, 6d and 9b emerged as the most active
      counterparts against VEGFR-2 with IC50 values of 0.1+/-0.01, 0.15+/-0.02, 0.28+/
      0.03 and 0.38+/-0.04 uM, respectively comparable to that of sorafenib (IC50 =
      0.1+/-0.02) uM. Furthermore, molecular docking studies were carried out for all
      synthesized compounds to investigate their binding pattern and predict their
      binding affinities towards VEGFR-2 active site. In silico ADMET studies were
      calculated for the tested compounds. Most of our designed compounds exhibited
      good ADMET profile.

PMID- 29651968
TI  - Design, Synthesis, Characterization, QSAR, Docking, Anti-inflammatory and
      Analgesic Evaluation of Some New Phthalazinediones.
AB  - BACKGROUND: phthalazine derivatives were reported to possess anticonvulsant ,
      cardiotonic , antibacterial, analgesic , anti-inflammatory, and anti-microbial
      activity. In the current study, we applied the QSAR for prediction of newly
      phthalazinediones incorporating thioamide moiety aiming to reach a more potent
      anti-inflammatory and Analgesic agent. METHODS: Phthalazinediones 10-15 have been
      synthesized through condensation of dibenzobarallene 3 with thiosemicarbazides 4
      8. One equation was predicted using quantitative structure activity relationship
      (QSAR) and regression analysis for the anti-inflammatory activity with a
      regression correlation (R) close to unity. The docking studies were performed to
      investigate the biological trends of the organic compounds (thiol form) against
      cyclooxygenas- 2 enzyme, which is a responsible inflammation mediator by using
      Molgro Virtual Docker (MVD) software. The anti-inflammatory activity and
      analgesic effect of the thioamides 10-15 were determined by collagen II-adjuvant
      induced paw edema test in rats. RESULTS: Compounds 10, 11, 12, and 14, exhibited
      promising anti-inflammatory activity. Furthermore, in the pain scoring, compounds
      10, 11 and 12 were found to be more effective than piroxicam and the order of the
      analgesic effect of the investigated compounds is as followed 14 >12 > 10 > 11 >
      15. CONCLUSION: It is clear from the foregoing that the compound 14 is a
      promising compound if future pharmacological detailed studies. This is consistent
      with what has been predictable equation 1 in this study.

PMID- 29651969
TI  - Synthesis, Characterization of Ethyl 5-(substituted)-1H-pyrazole- 3-carboxylate
      Derivative as Potent Anti-inflammatory Agents.
AB  - BACKGROUND: Recently, pyrazole derivatives have shown significant
      antiinflammatory activity. Non-steroidal anti-inflammatory drugs have some side
      effects, mainly gastric irritation and gastric ulceration during the treatment of
      inflammation. So the current study deals with the synthesis and pharmacological
      evaluation of a series of novel pyrazole derivatives as anti-inflammatory agents.
      METHODS: A series of novel ethyl 5-(substituted)-1H-pyrazole-3-carboxylate (2a-j)
      were synthesized and evaluated for anti-inflammatory activity using carrageenan
      induced inflammation in rat paw edema model. In the first step, diethyl oxalate
      react with acetophenone derivatives in presense of sodium ethoxide to form
      substituted ethyl-2,4-dioxo-4- phenyl butanoate derivatives as intermediate (1a
      j). Further the suspension was prepared from dioxo-esters with hydrazine hydrate
      in glacial acetic acid yielded novel ethyl 5- (substituted)-1H-pyrazole-3
      carboxylate (2a-j) derivatives. The structure of the final analogues (2a-j) has
      been confirmed on the basis of elemental analysis, IR, 1 H NMR and mass spectra.
      RESULTS: All the values of elemental analysis, FTIR, 1H NMR, and mass spectra
      were found to be prominent. The anti-inflammatory activity test revealed that
      Ethyl 5-(3,4- dimethoxyphenyl)-1H-pyrazole-3-carboxylate (2f) and ethyl 5-(2,3
      dimethoxyphenyl)-1Hpyrazole- 3-carboxylate (2e) exhibited significant anti
      inflammatory activity as compared to control group. CONCLUSION: The results of
      the current study indicate that the substitution at pyrazole scaffold could
      improve anti-inflammatory activity.

PMID- 29651970
TI  - Randomized Double-blind Placebo-controlled Trial of Celecoxib for the Prevention
      of Skin Toxicity in Patients Receiving Radiation Therapy for Breast Cancer.
AB  - BACKGROUND: The skin toxicity-induced by ionizing radiation may limit the
      duration of treatment and may lead to discomfort in quality of life of patients
      during radiotherapy. OBJECTIVE: The purpose of this randomized, placebo
      controlled, double-blind study was to investigate the preventive effect of oral
      administration of celecoxib (CLX) on the acute radiation- induced skin toxicity
      in patients with breast cancer. METHODS: Sixty breast cancer patients were
      randomly assigned to use CLX (400 mg per day) or placebo capsules during
      radiotherapy. Radiation-induced dermatitis was classified according to the
      radiation therapy oncology group (RTOG) criteria, as well as pain and itching
      were scored according to the VAS (Visual Analogue Scale) for six weeks of
      treatment. Breast swelling was evaluated through increase in the size of the
      breast during radiotherapy. RESULTS: Oral administration of CLX capsule during
      and after radiotherapy reduced significantly radiation-induced itching and pain
      in patients with breast cancer. CLX reduced the frequency of increased breast
      size caused by radiotherapy in patients as compared with placebo; however, this
      difference was statistically not significant. Patients who received CLX had
      insignificantly skin dermatitis when compared with placebo group. CONCLUSION:
      However, CLX was unable to reduce the dermatitis caused by ionizing radiation; it
      significantly reduced itching and pain in patients during radiotherapy. CLX may
      have beneficial effects in the quality life of breast cancer patients for
      treatment.

PMID- 29651971
TI  - Commentary: Stephen William Hawking (8 January 1942 - 14 March 2018).

PMID- 29651972
TI  - N-3 (Omega-3) Fatty Acids: Effects on Brain Dopamine Systems and Potential Role
      in the Etiology and Treatment of Neuropsychiatric Disorders.
AB  - BACKGROUND & OBJECTIVE: A number of neuropsychiatric disorders, including
      Parkinson's disease, schizophrenia, attention deficit hyperactivity disorder,
      and, to some extent, depression, involve dysregulation of the brain dopamine
      systems. The etiology of these diseases is multifactorial, involving genetic and
      environmental factors. Evidence suggests that inadequate levels of n-3 (omega- 3)
      polyunsaturated fatty acids (PUFA) in the brain may represent a risk factor for
      these disorders. These fatty acids, which are derived from the diet, are a major
      component of neuronal membranes and are of particular importance in brain
      development and function. Low levels of n-3 PUFAs in the brain affect the brain
      dopamine systems and, when combined with appropriate genetic and other factors,
      increase the risk of developing these disorders and/or the severity of the
      disease. This article reviews the neurobiology of n-3 PUFAs and their effects on
      dopaminergic function. CONCLUSION: Clinical studies supporting their role in the
      etiologies of diseases involving the brain dopamine systems and the potential of
      n-3 PUFAs in the treatment of these disorders are discussed.

PMID- 29651973
TI  - The Clinical and Immunological Features of Patients with Primary Antibody
      Deficiencies.
AB  - BACKGROUND: Primary antibody deficiency (PAD) comprises a range of diseases from
      early to late terminal B cells defects and is associated with the various
      clinical complications. METHODS: A total of 461 patients (311 males and 150
      females) with PADs enrolled in the retrospective cohort study and for all
      patients' demographic information, clinical records and laboratory data were
      collected to investigate clinical complications. RESULTS: The most prevalent
      first presentations of immunodeficiency were respiratory tract infections in
      63.5% and chronic diarrhea in 17.2%. Common variable immune deficiency (CVID)
      patients had a higher diagnostic delay than class switching defect (CSD), and
      agammaglobulinemia. Among the noninfectious complications, autoimmunity (26.2%),
      and splenomegaly (23.4%) were the most common. Lymphadenopathy was higher in CSD
      patients than other PADs, while splenomegaly, hepatomegaly, autoimmunity and
      bronchiectasis were more common in CVID patients than others. Atopic
      manifestations were mostly recorded in patients with selective IgA deficiency.
      Malignancy was only reported in 5.8% of patients with CVID. There was a higher
      prevalence of autoimmune manifestations in CVID comparing to other PADs.
      CONCLUSION: PADs are relatively rare diseases and these patients have a variety
      of first clinical manifestations, such as diverse infections, autoimmunity,
      lymphoproliferation, allergy, enteropathy and malignancy. Practitioner's
      awareness about the heterogeneous presentations of PAD disorders is poor,
      therefore patients often are lately diagnosed, and they are complicated with
      several clinical complications before the certain diagnosis.

PMID- 29651974
TI  - Preparation and Dosimetry Evaluation of a Carrier- Free 90Y Labeled DOTMP as a
      Promising Agent for Bone Marrow Ablation.
AB  - BACKGROUND AND OBJECTIVE: Skeletal uptake of 90Y-1,4,7,10-tetraazacyclododecane
      1,4,7,10- tetramethylene-phosphonate (DOTMP) is used to deliver high doses of
      this radiopharmaceutical to the bone marrow. METHODS: In this research, carrier
      free (c.f.) 90Y was obtained from an electrochemical 90Sr/90Y generator. The c.f.
      90Y was mixed with 300 uL of DOTMP (20 mg/mL) and incubated under stirring
      conditions at room temperature for 45 min. RESULTS: The [90Y]Y-DOTMP that was
      obtained under optimized reaction conditions had high radiochemical purities
      (>98%). Moreover, the radiolabeled complex exhibited excellent stability at room
      temperature, as well as in human serum. The biodistribution studies in rats
      showed the favorable selective skeletal uptake with rapid clearance from the
      blood, albeit with insignificant accumulation of activity in other non-target
      organs for the radiolabeled complex. Also, the present work has utilized the
      Monte Carlo codes MCNP-4C to simulate the depth dose profile for 90Y in a mice
      femur bone and compared with that produced by 153Sm and 177Lu. CONCLUSION: The
      results show that the absorbed dose produced by 90Y in the bone marrow is higher
      than 153Sm and 177Lu per 1MBq of the injected activity.

PMID- 29651975
TI  - Re-evaluating classical body type theories: genetic correlation between
      psychiatric disorders and body mass index.

PMID- 29651976
TI  - Screening for Anxiety and Depression in Epilepsy.

PMID- 29651977
TI  - Antimicrobial Resistance in Chlamydiales, Rickettsia, Coxiella, and Other
      Intracellular Pathogens.
AB  - This article will provide current insights into antimicrobial susceptibilities
      and resistance of an important group of bacterial pathogens that are not
      phylogenetically related but share lifestyle similarities in that they are
      generally considered to be obligate intracellular microbes. As such, there are
      shared challenges regarding methods for their detection and subsequent clinical
      management. Similarly, from the laboratory perspective, susceptibility testing is
      rarely undertaken, though molecular approaches might provide new insights. One
      should also bear in mind that the highly specialized microbial lifestyle
      restricts the opportunity for lateral gene transfer and, consequently,
      acquisition of resistance.

PMID- 29651978
TI  - Tracking the Rules of Transmission and Introgression with Networks.
AB  - Understanding how an animal organism and its gut microbes form an integrated
      biological organization, known as a holobiont, is becoming a central issue in
      biological studies. Such an organization inevitably involves a complex web of
      transmission processes that occur on different scales in time and space, across
      microbes and hosts. Network-based models are introduced in this chapter to tackle
      aspects of this complexity and to better take into account vertical and
      horizontal dimensions of transmission. Two types of network-based models are
      presented, sequence similarity networks and bipartite graphs. One interest of
      these networks is that they can consider a rich diversity of important players in
      microbial evolution that are usually excluded from evolutionary studies, like
      plasmids and viruses. These methods bring forward the notion of "gene
      externalization," which is defined as the presence of redundant copies of
      prokaryotic genes on mobile genetic elements (MGEs), and therefore emphasizes a
      related although distinct process from lateral gene transfer between microbial
      cells. This chapter introduces guidelines to the construction of these networks,
      reviews their analysis, and illustrates their possible biological interpretations
      and uses. The application to human gut microbiomes shows that sequences present
      in a higher diversity of MGEs have both biased functions and a broader microbial
      and human host range. These results suggest that an "externalized gut metagenome"
      is partly common to humans and benefits the gut microbial community. We conclude
      that testing relationships between microbial genes, microbes, and their animal
      hosts, using network-based methods, could help to unravel additional mechanisms
      of transmission in holobionts.

PMID- 29651979
TI  - RNases and Helicases in Gram-Positive Bacteria.
AB  - RNases are key enzymes involved in RNA maturation and degradation. Although they
      play a crucial role in all domains of life, bacteria, archaea, and eukaryotes
      have evolved with their own sets of RNases and proteins modulating their
      activities. In bacteria, these enzymes allow modulation of gene expression to
      adapt to rapidly changing environments. Today, >20 RNases have been identified in
      both Escherichia coli and Bacillus subtilis, the paradigms of the Gram-negative
      and Gram-positive bacteria, respectively. However, only a handful of these
      enzymes are common to these two organisms and some of them are essential to only
      one. Moreover, although sets of RNases can be very similar in closely related
      bacteria such as the Firmicutes Staphylococcus aureus and B. subtilis, the
      relative importance of individual enzymes in posttranscriptional regulation in
      these organisms varies. In this review, we detail the role of the main RNases
      involved in RNA maturation and degradation in Gram-positive bacteria, with an
      emphasis on the roles of RNase J1, RNase III, and RNase Y. We also discuss how
      other proteins such as helicases can modulate the RNA-degradation activities of
      these enzymes.

PMID- 29651980
TI  - Local Food Systems Food Safety Concerns.
AB  - Foodborne disease causes an estimated 48 million illnesses and 3,000 deaths
      annually (Scallan E, et al., Emerg Infect Dis 17:7-15, 2011), with U.S. economic
      costs estimated at $152 billion to $1.4 trillion annually (Roberts T, Am J Agric
      Econ 89:1183-1188, 2007; Scharff RL, http://www.pewtrusts.org/en/research-and
      analysis/reports/0001/01/01/healthrelated-costs-from-foodborne-illness-in-the
      united-states, 2010). An increasing number of these illnesses are associated with
      fresh fruits and vegetables. An analysis of outbreaks from 1990 to 2003 found
      that 12% of outbreaks and 20% of outbreak-related illnesses were associated with
      produce (Klein S, Smith DeWaal CS, Center for Science in the Public Interest,
      https://cspinet.org/sites/default/files/attachment/ddreport.pdf, June 2008; Lynch
      M, Tauxe R, Hedberg C, Epidemiol Infect 137:307-315, 2009). These food safety
      problems have resulted in various stakeholders recommending the shift to a more
      preventative and risk-based food safety system. A modern risk-based food safety
      system takes a farm-to-fork preventative approach to food safety and relies on
      the proactive collection and analysis of data to better understand potential
      hazards and risk factors, to design and evaluate interventions, and to prioritize
      prevention efforts. Such a system focuses limited resources at the points in the
      food system with the likelihood of having greatest benefit to public health. As
      shared kitchens, food hubs, and local food systems such as community supported
      agriculture are becoming more prevalent throughout the United States, so are
      foodborne illness outbreaks at these locations. At these locations, many with
      limited resources, food safety methods of prevention are rarely the main focus.
      This lack of focus on food safety knowledge is why a growing number of foodborne
      illness outbreaks are occurring at these locations.

PMID- 29651981
TI  - Lamotrigine for people with borderline personality disorder: a RCT.
AB  - BACKGROUND: No drug treatments are currently licensed for the treatment of
      borderline personality disorder (BPD). Despite this, people with this condition
      are frequently prescribed psychotropic medications and often with considerable
      polypharmacy. Preliminary studies have indicated that mood stabilisers may be of
      benefit to people with BPD. OBJECTIVE: To examine the clinical effectiveness and
      cost-effectiveness of lamotrigine for people with BPD. DESIGN: A two-arm, double
      blind, placebo-controlled individually randomised trial of lamotrigine versus
      placebo. Participants were randomised via an independent and remote web-based
      service using permuted blocks and stratified by study centre, the severity of
      personality disorder and the extent of hypomanic symptoms. SETTING: Secondary
      care NHS mental health services in six centres in England. PARTICIPANTS:
      Potential participants had to be aged >= 18 years, meet diagnostic criteria for
      BPD and provide written informed consent. We excluded people with coexisting
      psychosis or bipolar affective disorder, those already taking a mood stabiliser,
      those who spoke insufficient English to complete the baseline assessment and
      women who were pregnant or contemplating becoming pregnant. INTERVENTIONS: Up to
      200 mg of lamotrigine per day or an inert placebo. Women taking combined oral
      contraceptives were prescribed up to 400 mg of trial medication per day. MAIN
      OUTCOME MEASURES: Outcomes were assessed at 12, 24 and 52 weeks after
      randomisation. The primary outcome was the total score on the Zanarini Rating
      Scale for Borderline Personality Disorder (ZAN-BPD) at 52 weeks. The secondary
      outcomes were depressive symptoms, deliberate self-harm, social functioning,
      health-related quality of life, resource use and costs, side effects of treatment
      and adverse events. Higher scores on all measures indicate poorer outcomes.
      RESULTS: Between July 2013 and October 2015 we randomised 276 participants, of
      whom 195 (70.6%) were followed up 52 weeks later. At 52 weeks, 49 (36%) of those
      participants prescribed lamotrigine and 58 (42%) of those prescribed placebo were
      taking it. At 52 weeks, the mean total ZAN-BPD score was 11.3 [standard deviation
      (SD) 6.6] among those participants randomised to lamotrigine and 11.5 (SD 7.7)
      among those participants randomised to placebo (adjusted mean difference 0.1, 95%
      CI -1.8 to 2.0; p = 0.91). No statistically significant differences in secondary
      outcomes were seen at any time. Adjusted costs of direct care for those
      prescribed lamotrigine were similar to those prescribed placebo. LIMITATIONS:
      Levels of adherence in this pragmatic trial were low, but greater adherence was
      not associated with better mental health. CONCLUSIONS: The addition of
      lamotrigine to the usual care of people with BPD was not found to be clinically
      effective or provide a cost-effective use of resources. FUTURE WORK: Future
      research into the treatment of BPD should focus on improving the evidence base
      for the clinical effectiveness and cost-effectiveness of non-pharmacological
      treatments to help policy-makers make better decisions about investing in
      specialist treatment services. TRIAL REGISTRATION: Current Controlled Trials
      ISRCTN90916365. FUNDING: Funding for this trial was provided by the Health
      Technology Assessment programme of the National Institute for Health Research
      (NIHR) and will be published in full in Health Technology Assessment; Vol. 22,
      No. 17. See the NIHR Journals Library website for further project information.
      The Imperial Biomedical Research Centre Facility, which is funded by NIHR, also
      provided support that has contributed to the research results reported within
      this paper. Part of Richard Morriss' salary during the project was paid by NIHR
      Collaboration for Leadership in Applied Health Research and Care East Midlands.

PMID- 29651982
TI  - Response to comment on "Magnetosensitive neurons mediate geomagnetic orientation
      in Caenorhabditis elegans".
AB  - Many animals can orient using the earth's magnetic field. In a recent study, we
      performed three distinct behavioral assays providing evidence that the nematode
      Caenorhabditis elegans orients to earth-strength magnetic fields (<xref ref
      type="bibr" rid="bib28">Vidal-Gadea et al., 2015</xref>). A new study by Landler
      et al. suggests that C. elegans does not orient to magnetic fields (<xref ref
      type="bibr" rid="bib10">Landler et al., 2018</xref>). They also raise conceptual
      issues that cast doubt on our study. Here, we explain how they appear to have
      missed positive results in part by omitting controls and running assays longer
      than prescribed, so that worms switched their preferred migratory direction
      within single tests. We also highlight differences in experimental methods and
      interpretations that may explain our different results and conclusions. Together,
      these findings provide guidance on how to achieve robust magnetotaxis and
      reinforce our original finding that C. elegans is a suitable model system to
      study magnetoreception.

PMID- 29651983
TI  - Comment on "Magnetosensitive neurons mediate geomagnetic orientation in
      Caenorhabditis elegans".
AB  - A diverse array of species on the planet employ the Earth's magnetic field as a
      navigational aid. As the majority of these animals are migratory, their utility
      to interrogate the molecular and cellular basis of the magnetic sense is limited.
      Vidal-Gadea and colleagues recently argued that the worm Caenorhabditis elegans
      possesses a magnetic sense that guides their vertical movement in soil. In making
      this claim, they relied on three different behavioral assays that involved
      magnetic stimuli. Here, we set out to replicate their results employing blinded
      protocols and double wrapped coils that control for heat generation. We find no
      evidence supporting the existence of a magnetic sense in C. elegans. We further
      show that the Vidal-Gadea hypothesis is problematic as the adoption of a
      correction angle and a fixed trajectory relative to the Earth's magnetic
      inclination does not necessarily result in vertical movement.

PMID- 29651985
TI  - Smart bats click twice.
AB  - The acoustic representation of the outside world in the midbrain of a bat becomes
      more precise as it uses double clicks to locate closer objects.

PMID- 29651984
TI  - IFN-lambda prevents influenza virus spread from the upper airways to the lungs
      and limits virus transmission.
AB  - Host factors restricting the transmission of respiratory viruses are poorly
      characterized. We analyzed the contribution of type I and type III interferon
      (IFN) using a mouse model in which the virus is selectively administered to the
      upper airways, mimicking a natural respiratory virus infection. Mice lacking
      functional IFN-lambda receptors (Ifnlr1-/-) no longer restricted virus
      dissemination from the upper airways to the lungs. Ifnlr1-/- mice shed
      significantly more infectious virus particles via the nostrils and transmitted
      the virus much more efficiently to naive contacts compared with wild-type mice or
      mice lacking functional type I IFN receptors. Prophylactic treatment with IFN
      alpha or IFN-lambda inhibited initial virus replication in all parts of the
      respiratory tract, but only IFN-lambda conferred long-lasting antiviral
      protection in the upper airways and blocked virus transmission. Thus, IFN-lambda
      has a decisive and non-redundant function in the upper airways that greatly
      limits transmission of respiratory viruses to naive contacts.

PMID- 29651986
TI  - A pyrene formulation for fluorometric visualization of latent fingermarks.
AB  - Present work is conducted to demonstrate the use of pyrene for the development of
      latent fingermarks. Pyrene formulation with binders can be efficiently used for
      developing latent fingermarks on porous, non-porous and semi-porous surfaces. The
      effectiveness of pyrene formulation for the detection of latent fingermarks
      present on a large variety of objects was systematically and comparatively
      carried out. To optimize the working formulation, studies were carried out using
      different pyrene concentrations followed by various substrate study, time
      dependent study, temperature study, depleted fingermark development and the
      stability of the proposed formulation. When illuminated at 366 nm, the developed
      fingermarks showed clear, high contrast primary, secondary and tertiary level
      ridge details. This work reveals that the fluorescent molecules having high
      quantum yield are a versatile fluorescent label and can find their applications
      in forensic latent fingermark development.

PMID- 29651987
TI  - Measuring the excitations in a new S  =  1/2 quantum spin chain material with
      competing interactions.
AB  - Recently a new one-dimensional (1D) quantum spin chain system has been reported:
      catena-dichloro(2-Cl-3Mpy)copper(II), (where 2-Cl-3Mpy=2-chloro-3
      methylpyridine). Preliminary calculations and bulk magnetic property measurements
      indicate that this system does not undergo magnetic ordering down to 1.8 K and is
      a prime candidate for investigating frustration in a J 1/J 2 system (where the
      nearest neighbour interactions, J 1, are ferromagnetic and the next nearest
      neighbour interactions, J 2, are antiferromagnetic). Calculations predicted three
      possible magnetic interaction strengths for J 1 below 6 meV depending on the
      orientation of the ligand. For one of the predicted J 1 values, the existence of
      a quantum critical point is implied. A deuterated sample of catena-dichloro(2-Cl
      3Mpy)copper(II) was synthesised and the excitations measured using inelastic
      neutron scattering. Scattering indicated the most likely scenario involves spin
      chains where each chain consists of only one of the three possible magnetic
      excitations in this material, rather than the completely random array of exchange
      interactions within each chain as predicted by Herringer et al (2014 Chem. Eur.
      J. 20 8355-62). This indicates the possibility of tuning the chemical structure
      to favour a system which may exhibit a quantum critical point.

PMID- 29651988
TI  - Evaluation of a new method for the collection and measurement of 8-isoprostane in
      exhaled breath for future application in nanoparticle exposure biomonitoring.
AB  - BACKGROUND: In the field of nanoparticle exposure biomonitoring, oxidative stress
      biomarkers measured in exhaled breath condensate appear promising to detect early
      respiratory effects in workers handling nanomaterials. However, condensation is
      known for its poor efficiency in collecting non-volatiles in exhaled breath,
      leading to the low sensitivity of such measurements. Moreover, to be easily used
      in field studies on large groups of workers, the collection device must be
      disposable and convenient. OBJECTIVES: In this study, we have tested a totally
      disposable commercial device that allows for the easy dry collection of exhaled
      air after filtration on a patented filter. The suitability and efficiency of the
      SensAbues (SB) device for collecting 8-isoprostane were evaluated and compared to
      the RTube (RT). METHODS: Seven healthy volunteers performed two 15 min
      collections of exhaled breath, one with the SB and one with the RT. Blank devices
      were used to determine the background levels induced by each device. 8
      isoprostane was measured in all samples using an EIA technique. RESULTS: The
      levels of 8-isoprostane in the exhaled breath of volunteers after collection with
      the SB were significantly higher than those after collection with the RT.
      Moreover, the levels obtained in volunteers with the SB were significantly higher
      than background levels obtained in blank devices, which was not the case for the
      RT. CONCLUSIONS: This is the first study to report the ability of the SB device
      to collect and measure 8-isoprostane in exhaled breath. The proposed method
      offers better sensitivity than a classical collection with the RT device and
      should be further explored before future application in biomonitoring studies.

PMID- 29651989
TI  - Review of Saturn's icy moons following the Cassini mission.
AB  - We review our knowledge of the icy moons of Saturn prior to the Cassini orbital
      mission, describe the discoveries made by the instrumentation onboard the Cassini
      spacecraft.

PMID- 29651990
TI  - Non-Fermi liquids in oxide heterostructures.
AB  - Understanding the anomalous transport properties of strongly correlated materials
      is one of the most formidable challenges in condensed matter physics. For
      example, one encounters metal-insulator transitions, deviations from Landau Fermi
      liquid behavior, longitudinal and Hall scattering rate separation, a pseudogap
      phase, and bad metal behavior. These properties have been studied extensively in
      bulk materials, such as the unconventional superconductors and heavy fermion
      systems. Oxide heterostructures have recently emerged as new platforms to probe,
      control, and understand strong correlation phenomena. This article focuses on
      unconventional transport phenomena in oxide thin film systems. We use specific
      systems as examples, namely charge carriers in SrTiO3 layers and interfaces with
      SrTiO3, and strained rare earth nickelate thin films. While doped SrTiO3 layers
      appear to be a well behaved, though complex, electron gas or Fermi liquid, the
      rare earth nickelates are a highly correlated electron system that may be
      classified as a non-Fermi liquid. We discuss insights into the underlying physics
      that can be gained from studying the emergence of non-Fermi liquid behavior as a
      function of the heterostructure parameters. We also discuss the role of lattice
      symmetry and disorder in phenomena such as metal-insulator transitions in
      strongly correlated heterostructures.

PMID- 29651991
TI  - Ab initio effective deformation potentials of phosphorene and consistency checks.
AB  - Electron-phonon interaction in single-layer phosphorene is studied from first
      principles based on the density functional theory, using finite displacement
      method. Scattering rates and mobility are numerically evaluated for carriers in
      the conduction and valence bands. A criterion for the selection of phonon wave
      vector in scatterings is proposed. Scattering selection rules are studied,
      utilizing group theory for the structure with [Formula: see text] space group
      symmetry. Approximate analytical formulas for scattering rates, adopting the
      anisotropy intrinsic to phosphorene, are derived, and effective deformation
      potentials are evaluated by fitting the formulas to numerical scattering rates
      extracted from ab initio calculations.

PMID- 29651992
TI  - Two-photon oxygen nanosensors based on a conjugated fluorescent polymer doped
      with platinum porphyrins.
AB  - Ratiometric fluorescent nanoparticles (NPs) under two-photon excitation are
      successfully developed for sensing dissolved oxygen. The NPs comprise the oxygen
      probe Pt(II)-porphyrins (PtTFPP) and fluorescent organic semiconducting polymer
      (PFO). PFO polymer acts as both a two-photon antenna and a reference dye, while
      PtTFPP absorbs the photonic energy transferred by the PFO under two-photon
      excitation at 740 nm to sense oxygen. The red fluorescence of PtTFPP is sensitive
      to oxygen with a quenching response of 88% from nitrogen saturation to oxygen
      saturation, and PFO gives oxygen-insensitive referenced blue fluorescence. The
      fluorescence quenching of the NPs against oxygen at two-photon excitation follows
      a linear Stern-Volmer behavior. The nanosensors exhibit low cytotoxic effects as
      well as effortless cellular uptake. When incorporated into cells, the ratio of
      the signals increases up to about 500% from oxygen-saturated to oxygen-free
      environment.

PMID- 29651993
TI  - Effective field theory of chiral spin liquid between ordered phases in a kagome
      antiferromagnet.
AB  - We propose in this work an effective field theory description of the chiral spin
      liquid state in a Heisenberg spin system on a kagome lattice. To this end, we
      derive the low-energy effective theory of a kagome (isotropic) Heisenberg
      antiferromagnet around its ordered ground states found numerically and show that
      quantum fluctuations induced by further neighbor spin exchanges are equally
      strong as those from the first neighbor. We use a chiral order parameter theory
      to argue for the occurrence of finite temperature chiral symmetry breaking
      transition into a chiral ordered state in a kagome antiferromagnet with further
      neighbor spin exchange interactions. We compute the chiral symmetry breaking term
      in the effective ground state energy and show that chiral spin liquid necessarily
      occurs in the ground state of a kagome antiferromagnet with the first three
      nearest-neighbor spin exchange interactions. Finally, we consider the quantum
      criticality of the kagome antiferromagnet and show that a Chern-Simons term
      emerges naturally at the transition between the two ordered states that satisfy
      an appropriate 'matching condition' that we derive, providing an explanation for
      why chiral spin liquid could occur at the transition between appropriate ordered
      states. This emergent Chern-Simons term is the low energy effective theory of the
      chiral spin liquid state, where the chirality is the immediate consequence of the
      breaking of discrete symmetries by this topological field theory.

PMID- 29651994
TI  - Accurate quasiparticle calculation of x-ray photoelectron spectra of solids.
AB  - It has been highly desired to provide an accurate and reliable method to
      calculate core electron binding energies (CEBEs) of crystals and to understand
      the final state screening effect on a core hole in high resolution x-ray
      photoelectron spectroscopy (XPS), because the DeltaSCF method cannot be simply
      used for bulk systems. We propose to use the quasiparticle calculation based on
      many-body perturbation theory for this problem. In this study, CEBEs of band
      gapped crystals, silicon, diamond, beta-SiC, BN, and AlP, are investigated by
      means of the GW approximation (GWA) using the full omega integration and compared
      with the preexisting XPS data. The screening effect on a deep core hole is also
      investigated in detail by evaluating the relaxation energy (RE) from the core and
      valence contributions separately. Calculated results show that not only the
      valence electrons but also the core electrons have an important contribution to
      the RE, and the GWA have a tendency to underestimate CEBEs due to the excess RE.
      This underestimation can be improved by introducing the self-screening correction
      to the GWA. The resulting C1s, B1s, N1s, Si2p, and Al2p CEBEs are in excellent
      agreement with the experiments within 1 eV absolute error range. The present self
      screening corrected GW approach has the capability to achieve the highly accurate
      prediction of CEBEs without any empirical parameter for band-gapped crystals, and
      provide a more reliable theoretical approach than the conventional DeltaSCF-DFT
      method.

PMID- 29651995
TI  - Investigation of TbMn2O5 by polarized neutron diffraction.
AB  - In order to make a new approach to the elucidation of the microscopic mechanisms
      of multiferroicity in the RMn2O5 family, experiments with different methods of
      polarized neutrons scattering were performed on a TbMn2O5 single crystal. We
      employed three different techniques of polarized neutron diffraction without the
      analysis after scattering, the XYZ-polarization analysis, and technique of
      spherical neutron polarimetry (SNP). Measurements with SNP were undertaken both
      with and without external electric field. A characteristic difference in the
      population of 'right' and 'left' helix domains in all magnetically ordered phases
      of TbMn2O5, was observed. This difference can be controlled by an external
      electric field in the field-cooled mode. The analysis of the results gives an
      evidence that antisymmetric Dzyaloshinsky-Moria exchange is effective in all the
      magnetic phases in TbMn2O5.

PMID- 29651996
TI  - Superconductivity switch from spin-singlet to -triplet pairing in a topological
      superconducting junction.
AB  - The interedge coupling is the cardinal characteristic of the narrow quantum spin
      Hall (QSH) insulator, and thus could bring about exotic transport phenomena.
      Herein, we present a theoretical investigation of the spin-resolved Andreev
      reflection (AR) in a QSH insulator strip touching on two neighbouring
      ferromagnetic insulators and one s-wave superconductor. It is demonstrated that,
      due to the interplay of the interedge coupling and ferromagnetic configuration,
      there could be not only usual local ARs leading to the spin-singlet pairing with
      the incident electron and Andreev-reflected hole from different spin subbands,
      but also novel local ARs giving rise to the spin-triplet pairing from the same
      spin subband. However, only the latter exists in the absence of the interedge
      coupling, and therefore the two pairings in turn testify the helical spin texture
      of the edge states. By proper tuning of the band structures of the ferromagnetic
      layers, under the resonance bias voltage, the usual and novel local ARs of
      [Formula: see text] can be all exhibited, resulting in fully spin-polarized pure
      spin-singlet superconductivity and pure spin-triplet superconductivity,
      respectively, which suggests a superconductivity switch from spin-singlet to 
      triplet pairing by electrical control. The results can be experimentally
      confirmed by the tunneling conductance and the noise power.

PMID- 29651997
TI  - Ba9V3Se15: a novel compound with spin chains.
AB  - In this work, a novel compound Ba9V3Se15 with one-dimensional (1D) spin chains
      was synthesized under high-pressure and high-temperature conditions. It was
      systematically characterized via structural, magnetic, thermodynamic and
      transport measurements. Ba9V3Se15 crystallizes into a hexagonal structure with a
      space group of P-6c2 (188) and the lattice constants of a  =  b  =  9.5745(7) A
      and c  =  18.7814(4) A. The crystal structure consists of face-sharing octahedral
      VSe6 chains along c axis, which are trimeric and arranged in a triangular lattice
      in ab-plane. Ba9V3Se15 is a semiconductor and undergoes complex magnetic
      transitions. In the zero-field-cooled (ZFC) process with magnetic field of 10 Oe,
      Ba9V3Se15 sequentially undergoes ferrimagnetic and spin cluster glass transition
      at 2.5 K and 3.3 K, respectively. When the magnetic field exceeds 50 Oe, only the
      ferrimagnetic transition can be observed. Above the transition temperature, the
      specific heat contains a significant magnetic contribution that is proportional
      to T 1/2. The calculation suggests that the nearest neighbor (NN) intra-chain
      antiferromagnetic exchange J 1 is much larger than the next nearest neighbor
      (NNN) intra-chain ferromagnetic exchange J 2. Therefore, Ba9V3Se15 can be
      regarded as an effective ferromagnetic chains with effective spin-1/2 by the
      formation of the V(2)(?) V(1)(?) V(2)(?) cluster.

PMID- 29651998
TI  - High-resolution local field potentials measured with deep brain stimulation
      arrays.
AB  - OBJECTIVE: Local field potential (LFP) recordings along a deep brain stimulation
      (DBS) lead can provide useful feedback for titrating DBS therapy. However,
      conventional DBS leads with four cylindrical macroelectrodes likely undersample
      the spatial distribution of sinks and sources in a given brain region. In this
      study, we investigated the spectral power and spatial feature sizes of LFP
      activity in non-human primate subthalamic nucleus and globus pallidus using
      chronically implanted 32-channel directional DBS arrays. APPROACH: Subthalamic
      nucleus and globus pallidus LFP signals were recorded from directional DBS arrays
      in the resting state and during a reach-and-retrieval task in two non-human
      primates in naive and parkinsonian conditions. LFP recordings were compared
      amongst bipolar pairs of electrodes using individual and grouped electrode
      configurations, with the latter mimicking the cylindrical macroelectrode
      configurations used in current clinical LFP recordings. MAIN RESULTS: Recordings
      from these DBS arrays showed that (1) beta oscillations have spatial
      'fingerprints' in the subthalamic nucleus and globus pallidus, and (2) that these
      oscillations were muted when grouping electrode contacts together to create
      cylindrical macroelectrodes similar in relative dimension to those used
      clinically. Further, these maps depended on parkinsonian condition and whether
      the subject was resting or performing a motor task. SIGNIFICANCE: Development of
      future closed-loop DBS therapies that rely on LFP feedback will benefit from
      implanting DBS arrays with electrode sizes and spacings that are more consistent
      with the dimensions of oscillatory sinks and sources within the brain.

PMID- 29652000
TI  - Exciting times.

PMID- 29651999
TI  - Photolithographic-stereolithographic-tandem fabrication of 4D smart scaffolds for
      improved stem cell cardiomyogenic differentiation.
AB  - 4D printing is a highly innovative additive manufacturing process for fabricating
      smart structures with the ability to transform over time. Significantly different
      from regular 4D printing techniques, this study focuses on creating novel 4D
      hierarchical micropatterns using a unique photolithographic-stereolithographic
      tandem strategy (PSTS) with smart soybean oil epoxidized acrylate (SOEA) inks for
      effectively regulating human bone marrow mesenchymal stem cell (hMSC)
      cardiomyogenic behaviors. The 4D effect refers to autonomous conversion of the
      surficial-patterned scaffold into a predesigned construct through an external
      stimulus delivered immediately after printing. Our results show that hMSCs
      actively grew and were highly aligned along the micropatterns, forming an
      uninterrupted cellular sheet. The generation of complex patterns was evident by
      triangular and circular outlines appearing in the scaffolds. This simple, yet
      efficient, technique was validated by rapid printing of scaffolds with well
      defined and consistent micro-surface features. A 4D dynamic shape change
      transforming a 2-D design into flower-like structures was observed. The printed
      scaffolds possessed a shape memory effect beyond the 4D features. The advanced 4D
      dynamic feature may provide seamless integration with damaged tissues or organs,
      and a proof of concept 4D patch for cardiac regeneration was demonstrated for the
      first time. The 4D-fabricated cardiac patch showed significant cardiomyogenesis
      confirmed by immunofluorescence staining and qRT-PCR analysis, indicating its
      promising potential in future tissue and organ regeneration applications.

PMID- 29652001
TI  - Economic impact of dental caries in India.

PMID- 29652002
TI  - Evaluation of bioflavonoids on the immediate and delayed microtensile bond
      strength of self-etch and total-etch adhesive systems to sound dentin.
AB  - Aim: This study aims to evaluate the effect of two bioflavonoids
      (epigallocatechin-3-gallate [EGCG] and catechin) and a protein inhibitor
      (chlorhexidine [CHX]) on the immediate and delayed microtensile bond strength of
      self-etch and total-etch adhesive systems to sound dentin. Materials and Methods:
      The occlusal surfaces of 96 mandibular human third molar teeth specimens were
      ground after removal of the excess tissues, to expose the middle dentin. The
      dentin specimens were randomly allocated into four groups, each consisting of 24
      teeth (n = 24) according to the application of the enzyme inhibitor. The adhesive
      system used in this study was Adper easy bond, a self-etch adhesive system, and
      Adper Single Bond 2, a total-etch adhesive system. Microtensile bond strength
      testing was conducted using thermocycler 2000, Heto-Holten A/S. Results: All the
      three enzyme inhibitors increase the bond strength values of the resin-dentin
      interphase when used during dentin bonding. The EGCG enzyme inhibitor has shown
      the highest immediate bond strength to dentin when used with both the adhesive
      systems.

PMID- 29652003
TI  - Angular photogrammetric analysis of the soft-tissue facial profile of Indian
      adults.
AB  - Introduction:: Soft-tissue analysis has become an important component of
      orthodontic diagnosis and treatment planning. Photographic evaluation of an
      orthodontic patient is a very close representation of the appearance of the
      person. The previously established norms for soft-tissue analysis will vary for
      different ethnic groups. Thus, there is a need to develop soft-tissue facial
      profile norms pertaining to Indian ethnic groups. Aim and Objectives:: The aim of
      this study is to establish the angular photogrammetric standards of soft-tissue
      facial profile for Indian males and females and also to compare sexual dimorphism
      present between them. Materials and Methods: The lateral profile photographs of
      300 random participants (150 males and 150 females) between ages 18 and 25 years
      were taken and analyzed using FACAD tracing software. Inclusion criteria were
      angles Class I molar occlusion with acceptable crowding and proclination, normal
      growth and development with well-aligned dental arches, and full complements of
      permanent teeth irrespective of third molar status. This study was conducted in
      Indian population, and samples were taken from various cities across India.
      Descriptive statistical analysis was carried out, and sexual dimorphism was
      evaluated by Student's t-test between males and females. Results: The results of
      the present study showed statistically significant (P < 0.05) gender difference
      in 5 parameters out of 12 parameters in Indian population. Conclusion: In the
      present study, soft-tissue facial measurements were established by means of
      photogrammetric analysis to facilitate orthodontists to carry out more
      quantitative evaluation and make disciplined decisions. The mean values obtained
      can be used for comparison with records of participants with the same
      characteristics by following this photogrammetric technique.

PMID- 29652004
TI  - Factors associated with patients' satisfaction of rubber dam use during root
      canal treatment.
AB  - Background: The use of rubber dam (RD) has been recommended in dental procedures
      including root canal treatment. The aim of the study was to identify factors that
      were associated with patients' satisfaction and acceptance of RD. Setting and
      Design:: This was a cross-sectional study, conducted from January 2015 to
      December 2016 at Kuwait University School of Dentistry. Materials and Methods: A
      pretested questionnaire was used by a face-to-face interview of patients after
      taking informed consent. The study was approved by the Institutional Ethics
      Review Board. The providers/operators who applied RD were grouped into three
      categories: undergraduate final year (7th year) dental students; general dentists
      and postgraduate students; and specialists. Results: Mean age of the patients (n
      = 175) was 31.6 +/- 13.0 years. About 55% had past experience, and 52% expressed
      a better experience during the current procedure compared with the previous one.
      A positive experience during the current procedure correlated significantly with
      the future intention of RD use (r = 0.244, P = 0.001). Time needed for RD
      application was short (4 min), irrespective of the operators. The duration of RD
      use during the procedure was significantly shorter among dental specialists
      compared with the other groups. Time for RD application was the only significant
      predictor for patient satisfaction, after controlling for other independent
      variables. Conclusion: Based on the positive influence of current RD use on the
      future intention, dentists should spend time needed to explain the importance,
      safety and effectiveness of RD use with their patients.

PMID- 29652005
TI  - Association between traditional oral hygiene methods with tooth wear, gingival
      bleeding, and recession: A descriptive cross-sectional study.
AB  - Background: Oral hygiene maintenance is crucial for prevention of various oral
      diseases. Oral hygiene practices across the country vary largely and people in
      peri-urban and rural areas use traditional methods of oral hygiene like powders,
      bark, oil and salt etc. Their effect on oral soft and hard tissues need to be
      studied to understand their beneficial and/ or harmful effects on maintenance of
      oral hygiene and prevention or causation of oral diseases. Objectives: This study
      aimed to assess the plaque-cleaning efficacy, gingival bleeding, recession and
      tooth wear with different traditional oral hygiene methods as compared to use of
      toothpaste-toothbrush, the most accepted method of oral hygiene practice. Study
      Design: Hospital based cross sectional analytical study. Results: Total 1062
      traditional oral hygiene method users were compared with same number of
      toothpaste-brush users. The maximum number in the former group used tooth powder
      (76%) as compared to other indigenous methods, such as use of bark of trees etc
      and out of tooth powder users; almost 75% reported using red toothpowder. The
      plaque scores and gingival bleeding & recession were found to be more in
      traditional oral hygiene method users. The toothwear was also more severe among
      the toothpowder users. Conclusions: Traditional methods were found to be inferior
      in plaque control as was documented by increased bleeding and gingival recession.
      Its effect on hard tissues of teeth was very damaging with higher tooth wear
      scores on all surfaces.

PMID- 29652006
TI  - Comparison of interpupillary distance and combined mesiodistal width of maxillary
      central incisor teeth in two ethnic groups of Northeast India: An in vivo study.
AB  - Background: Anthropometric measurements of the face can be used as a guide in
      selecting proper sized anterior teeth. Aim: The aim of this study is to evaluate
      the relationship between the interpupillary distance (IPD) and the combined
      mesiodistal width of maxillary central incisors (MDW of MCIs) to establish their
      morphometric criterion and their significance in two ethnic groups of Northeast
      India. Methodology: A total of 120 participants consisting of 60 indigenous
      students each from Assam and Meghalaya in the age group of 18-25 years were
      selected after taking their written consent. Standardized facial frontal
      photographs of all the participants were taken using a digital camera in such a
      manner that maxillary anterior teeth were visible. The photographs were uploaded
      onto the computer and saved in a file. Anthropometric measurements of IPD and
      combined MDW of MCIs in centimeters were made using both Adobe Photoshop(r) 7.0
      software program and manually using a digital vernier caliper on the developed
      photographs to a same size of 15 cm * 10 cm. Data obtained were tabulated and
      analyzed using Student "t"-test and Pearson correlation test. Results: The
      present study reveals a positive correlation with a high degree of statistical
      significance between IPD and combined mesiodistal width of maxillary central
      incisors among all the samples irrespective of gender and ethnicity where P <
      0.01. Conclusion: IPD can be used as a guide in determining the suitable
      mesiodistal dimension of the maxillary central incisors.

PMID- 29652007
TI  - Objective and subjective parameters of oral health in South Indian children: A
      cross-sectional study.
AB  - Background: Oral health of schoolchildren is a strong predictor of their overall
      well-being. This study was planned to assess and compare the objective and
      subjective parameters of oral health of South Indian school children.
      Methodology: Three hundred and sixty school children participated in this cross
      sectional study. Their oral hygiene status, dental caries status, and treatment
      needs were assessed. Two questionnaires were filled by these children, to assess
      their oral health-related quality of life (OHRQoL) and their knowledge on oral
      health. Their academic scores were collected from the schools. Statistical
      analysis was done using Kruskal-Wallis ANOVA test and Spearman correlation test
      appropriately. Results: Children with no caries had better OHRQoL (P = 0.02).
      There was a negative correlation between dental caries status and OHRQoL score (P
      = 0.003) and dental caries treatment needs and OHRQoL score (P = 0.01). There was
      a positive correlation between knowledge on oral health and OHRQoL score (P =
      0.02). Conclusion: Children with no caries had a better OHRQoL when compared to
      children with caries. Children with caries had more treatment needs, poor oral
      hygiene, low quality of life, and performed lesser in academics. However, they
      had adequate knowledge on oral health. Hence, both objective and subjective
      parameters of oral health should be given importance while treating children.

PMID- 29652008
TI  - Efficacy of autogenous fascia lata and silicone aurosling in correction of
      congenital blepharoptosis by frontalis suspension.
AB  - Purpose: The purpose of this study is to assess the outcomes of frontalis sling
      using fascia lata and silicone aurosling for congenital unilateral ptosis
      patients with poor levator function. Material and Methods: Retrospective study of
      archival cases from 22 patients from author's center. All the patients with
      unilateral ptosis with poor levator function were included excluding those having
      poor Bell's phenomenon and associated pathology like jaw winking, 3rd nerve
      misdirection, squint, impaired corneal sensitivity, and neoplastic lesions.
      Patients were diagnosed based on the history and clinical examination including
      measurements. Corrections were performed by single surgeon. Marginal reflex
      distance-1 (MRD1) values observed preoperatively, immediate postoperatively, and
      late postoperatively in both groups. Results: : Of the 22 cases, 12 were treated
      with fascia while the remaining 10 were treated with silicone aurosling material.
      The mean age of the fascia group was 11.42 +/- 3.55 years while it was 14 +/- 4.2
      years for the silicone group. There were 10 males and 12 females in the study
      group. The mean follow-up in the study group was 20.14 +/- 2.05 months, and the
      difference between the groups was not statistically significant. The difference
      between the two groups at the preoperative and immediate postoperative did not
      vary with statistical significance (P = 0.926 and P = 0.242, respectively). The
      late postoperative MRD1 did vary significantly between the two groups. The mean
      late postoperative MRD1 for fascia group was 3.67 +/- 0.32 with a range of 3.1
      4.15 while for the silicone group was 3.2 +/- 0.46 with a range of 2.5-4. The
      difference was statistically significant (P = 0.023). Discussion and Conclusion:
      The stability of the change in silicone aurosling group was relatively less as
      compared to the fascia lata. The recent material aspect study of such silicone
      aurosling material indicates that they are susceptible to damage and that cause
      the loss of stability. More studies with larger sample size and longer follow-up
      are needed.

PMID- 29652009
TI  - Immunohistochemical expression of polo-like kinase 1 in oral squamous cell
      carcinoma and oral submucous fibrosis.
AB  - Context: Polo-like kinase 1 (PLK1) is a critical molecule in the proliferation of
      several human cancers. Overexpression of PLK1 has been correlated with cancer
      cell proliferation and lower overall survival rates. Although PLK1 has been
      studied in various tumors, information regarding its expression in oral cancer
      and precancer is limited. Aims: This study is aimed at evaluating the expression
      of PLK1 in a potentially malignant and malignant disorder of the oral cavity,
      namely, oral submucous fibrosis (OSMF) and oral squamous cell carcinoma (OSCC),
      respectively, using the immunohistochemistry technique. It also intended to
      evaluate the association of the various histological grades of OSCC with the
      intensity of PLK1 expression. Subjects and Methods: Thirty OSMF, thirty OSCC
      tissues, and thirty control tissues were obtained, and the expression of PLK1 was
      detected by immunohistochemistry using rabbit antihuman PLK1 polyclonal
      antibodies (Abcam Ab47867). The association between staining intensity and
      histological grade of OSCC was evaluated. Statistical Analysis Used: Using SPSS
      20 version, a test for proportions, nonparametric Chi-square/correlation analysis
      was used to compare differences in proportions of categorical variables of
      interest between groups. Results: PLK1 was positively expressed in 27 (90%) OSCC
      tissues. OSMF showed no detectable staining in 27 (90%) tissues and positive
      staining in 3 (10%) tissues. PLK1 showed no staining (0%) in normal tissues.
      Statistically significant associations were not found between staining intensity
      and histological grade of OSCC. Conclusions: PLK1 could be a promising
      progression marker for OSCC. Therapeutically, targeting PLK1 may be a new
      approach to fight oral cancer.

PMID- 29652010
TI  - A survey on the use of various gingival displacement techniques in fixed partial
      denture by the prosthodontists in vadodara city.
AB  - Aims: To evaluate the use of various gingival displacement techniques prior to
      impression making in fixed partial dentures by the Prosthodontists in Vadodara.
      Settings and Design: Questionnaire based survey among prosthodontists in Vadodara
      city. Methods and Material: All the prosthodontists practitioners and those
      prosthodontists in academic institutes in Vadodara City, Gujarat, were surveyed
      through a questionnaire regarding their usage of gingival displacement technique
      and their reasons and methods of using gingival displacement technique for fixed
      partial denture. The results were analysed through discriminant statistical
      analysis. Results: Among all the Prosthodontists in Vadodara city, 62% prefer the
      use of gingival displacement technique for successful clinical practice while 38
      % of them do not follow the procedure believing it does not make major difference
      in clinical practice. Conclusions: Those Prosthodontists who preferred the use of
      gingival displacement technique were able to detect many advantages of using it
      in their daily fixed partial denture practice and the percentage of
      prosthodontists not following gingival displacement technique blamed it as a time
      consuming affair and was not feasible on economic grounds for the class of
      patient they treated.

PMID- 29652011
TI  - Quest for haller cells: A digital orthopantomography study.
AB  - Aims: Haller Cells refer to the ethmoidal pneumatization and are the extensions
      of anterior ethmoid sinus into the floor of the orbit and superior aspect of the
      maxillary sinus, basically an anatomic variation. They may be associated with
      orofacial pain, sinusitis, nasal obstruction, impaired nasal breathing, headache,
      chronic cough, and mucocele. The aim of the present study was to identify,
      determine the prevalence and characteristics of Haller's cells on Digital
      orthopantomographs in patient's reporting to a dental institution in Chennai.
      Settings and Design:: This was a retrospective, cross-sectional study. Subjects
      and Methods: The study group comprised 600 radiographs inclusive of both genders
      (379 females and 221 males) with an age range of 20-80 years. Retrospectively
      panoramic radiograph for each of the patients was viewed and interpreted for the
      presence of Haller's cells. The data collected was subjected to statistical
      analysis: frequencies/percentages, descriptive statistics to obtain the results.
      Statistical Analysis Used: Frequencies/percentages, descriptive statistics using
      SPSS for Windows Version 20 (SPSS Inc., Chicago, IL, USA), to obtain the results.
      Results: Haller's cells were noted in patients, accounting for a prevalence of
      23.61%. The majority of the cells were circular, ovoid, and irregular in shape.
      Conclusions: This study has attempted to explore the characteristics of Haller's
      cells on panoramic radiographs. A description of Haller's cells on these
      radiographs may prove vital in enumerating the differential diagnosis for
      patients afflicted with intractable orofacial pain and reduce the risk of
      untoward intraoperative complications during endonasal procedures.

PMID- 29652012
TI  - Nature and pattern of primary teeth extractions in a tertiary care hospital
      setting in South India.
AB  - Background: Many studies have been carried out on the prevalence of dental
      diseases in children although not much information is available regarding its
      outcome among Indian children. Aim: The aim of the present study was to analyze
      the type of primary tooth extracted and the reasons for the extraction among
      children attending a tertiary care hospital in the Southern part of India.
      Materials and Methods: The dental records of pediatric patients who had visited
      the dental clinic of a tertiary care hospital located in Tamil Nadu, South India
      from December 2013 to November 2016 were reviewed. Patients who underwent
      extraction of at least one primary tooth under local or general anesthesia were
      included in the study. Results: A total of 943 primary teeth were extracted from
      447 patients over 3 years. The most commonly extracted tooth type was the first
      primary molar followed by the primary central incisor. Grouping by age, the most
      frequently extracted tooth type between 2 and 5 years was the primary central
      incisor, the first primary molar among the 6-9-year-old and the second primary
      molar among 10-15-year-old. The majority of primary teeth extractions were
      performed in the age group of 6-9 years. No significant gender differences were
      noted. The most common reason for extraction of primary teeth in children was
      dental caries. Conclusions: This study demonstrates a high prevalence of untimely
      primary teeth extractions in young children and dental caries continues to be the
      leading cause. It clearly reflects on the lack of infant oral health care, the
      inadequacy of awareness and underutilization of oral health services among
      children in India.

PMID- 29652013
TI  - Changing trends in maxillofacial trauma: A 15 years retrospective study in the
      Southern Part of Haryana, India.
AB  - Objective: The aim is to analyze the pattern of maxillofacial injuries and
      treatment outcomes in the past 15 years (2002-2016). Materials and Methods:: One
      thousand eight hundred and fifty patients from two tertiary referral center
      hospitals were studied retrospectively in which the age, sex, etiology, site of
      fracture, and treatment modality was recorded. Results: One thousand two hundred
      and twenty-eight males and 622 females were operated between 2002 and 2016. Mean
      age was 29 +/- 17.2 years. Maximum incidence was seen in the age group of 16-30
      years in males, whereas in females, the predominance of trauma was seen in both
      16-30 and 31-45 age groups. Road traffic accidents were responsible for the
      majority of fractures (42.2%), followed by assaults (26.4), sports injuries
      (17.6%), and fall (10.7%). Maximum fractures were of the mandible (53.5%)
      followed by midface (25.6%) and panfacial trauma (20.8%). Nearly 53.6% of
      patients underwent open reduction, and internal fixation (ORIF), 34.2% managed by
      the closed method and 12.1% were kept under observation. Conclusion: This study
      verified a young male predominance, a shift toward more assault related
      fractures, especially in females. Mandibular fractures were the most common of
      all. Moreover, the changing trend toward ORIF in the past 15 years.

PMID- 29652014
TI  - BCL-X expression in oral cancer: Comparison between oral squamous cell carcinoma
      and verrucous carcinoma.
AB  - Background: Verrucous carcinoma (VC) should be considered a distinct
      clinicopathologic entity different from the more common oral squamous cell
      carcinoma (OSCC) because of its unique biological behavior. Best way to
      understand the behavior of these carcinomas is to study them by means of
      molecular methods, especially in tumor progression tests and Bcl-X is an
      important antiapoptotic member of the Bcl-2 family and is one of the newest and
      most useful markers to determine the aggressiveness of many carcinomas. The
      relationship between this Bcl-X protein and carcinomatous behavior toward it is
      not studied extensively, which we attempted to evaluate using immunohistochemical
      analysis in selected carcinomas of the head and neck region. Method: We studied
      Bcl-X protein expression in sections of thirty OSCC and ten VC samples and
      correlated this with tumor differentiation. Results: There was a significant
      difference in cytoplasmic staining of Bcl-X expression with statistical analysis
      (P < 0.005) for VC and OSCC when compared as a group. No significance was seen
      among the different histological grades of OSCC and when compared with VC
      individually. Conclusion: The significant result between OSCC and VC suggests
      that their biologic course is comparable and can be helpful in differentiating
      them with each other for establishment of a better treatment protocol.

PMID- 29652015
TI  - A comparative evaluation of the staining capacity of microhybrid and nanohybrid
      resin-based composite to indian spices and food colorants: An In vitro study.
AB  - Introduction: Resin composite restorative materials can mimic the natural color
      and shade of the tooth. However, exogenous colorants from food and drinks can
      stain them due to adsorption. The influence of Indian food colorants and spices
      on resin composite restorations has not been evaluated extensively. Aim: This
      study aims to evaluate the staining capacity of microhybrid and nanohybrid resin
      based composites, to saffron extract, tandoori powder, and turmeric powder.
      Subjects and Methods: Forty samples of microhybrid (Kulzer Charisma) and
      nanohybrid (3M Filtek Z350) resin composites were prepared using an acrylic
      template of dimension 5 mm * 3 mm. They were randomly divided into four groups
      and immersed into solutions of saffron extract, tandoori powder, and turmeric
      powder. Distilled water was used as the control group. Color values (LFNx01,
      aFNx01, bFNx01) were measured by colorimeter using the CIE LFNx01aFNx01bFNx01
      system before and after 72 h of immersion. Color differences DeltaEFNx01ab were
      statistically analyzed. Statistical Analysis Used: Two-way ANOVA and post-hoc
      Tukey (honest significant difference) test were done using IBM SPSS Statistics
      for Windows, Version 19.0. Armonk, NY: IBM Corp. Results and Discussion: : All
      the immersion media changed the color of the resin composites to varying degrees.
      However, turmeric solution showed the maximum mean color variation DeltaEFNx01ab
      of 14.8 +/- 2.57 in microhybrid resin composites and 16.8 +/- 3.50 in nanohybrid
      resin composites. Conclusion: Microhybrid and nanohybrid resin composites tend to
      stain to Indian food colorants, especially to turmeric powder.

PMID- 29652016
TI  - Effect of inadequate ferrule segment location on fracture resistance of
      endodontically treated teeth.
AB  - Introduction: The circumferential 2 mm ferrule during the fabrication of the
      crown is strongly advocated for the long-term clinical success. During the
      routine clinical practice, the dentist encounters the endodontically treated
      tooth (ETT) with inadequacy of the ferrule in some segment due to caries,
      abrasion, and erosions. The aim of this in vitro study was to investigate the
      consequence of inadequate segmental ferrule location on fracture strength of the
      root canal-treated anterior and posterior teeth. Materials and Methods: Fifty
      each maxillary canine and mandibular premolar intact human teeth were root canal
      treated and sectioned at 2 mm above the cementum-enamel junction. The teeth
      samples were divided into 5 groups of 10 each. The G-I and G-V samples had the
      360 degrees  ferrule and complete absence of the ferrule, respectively. The G-II
      had the inadequate ferrule on the palatal surface, while G-III and G-IV had
      inadequate ferrule at buccal and proximal area. Teeth samples were subsequently
      restored with glass-reinforced fiber post, composite core, and full veneer metal
      crown. The samples were tested with universal testing machine under static load
      to record the fracture resistance. The acquired data were subjected to ANOVA and
      Tukey's post hoc statistical analysis. Results: The G-I with circumferential
      ferrule showed the higher fracture resistance. The teeth samples with lack of the
      ferrule had the least fracture resistance. Among the segmental absence of
      ferrule, teeth samples with lack of the proximal ferrule were least affected.
      Deficiency of a ferrule on the lingual wall significantly affected the fracture
      strength in both anterior and posterior ETT. Conclusions: The ETT with sectional
      inadequacy of the ferrule is significantly more effective in resisting the
      fracture in comparison to the complete absence of the ferrule.

PMID- 29652017
TI  - Evaluation of kinetic friction between regular and colored titanium molybdenum
      alloy archwires.
AB  - Aim: The aim of this study was to evaluate the kinetic frictional properties of
      colored titanium molybdenum alloy (TMA) archwires (purple-coated TMA and honey
      dew-coated TMA) and the regular TMA archwires. Materials and Methods: The
      experiment comprised of three groups, Group I - Regular TMA archwires, Group II -
      Purple-coated TMA archwires, Group III - Honey dew-coated TMA wires involving 21
      samples each that were evaluated for their frictional properties using Instron
      Universal Testing Machine. Results: The results were subjected to statistical
      analysis using analysis of variance wherein Group I Regular TMA wires revealed
      mean kinetic frictional value of 8.236 N and a standard deviation of 0.4038 N,
      while Group II (purple-coated TMA wires) showed a mean value of 5.297 N, standard
      deviation of 0.3128 N and Group III (honey dew-coated TMA wires) showed a mean
      value of 4.206 N and a standard deviation of 0.5353 N. Conclusion: The kinetic
      frictional values are higher for regular TMA wire exhibiting superior
      characteristic of color-coated TMA. Wires exhibiting superior characteristics are
      color-coated TMA wires, especially honey dew-coated TMA wires over the regular
      and purple-coated TMA wires. These superior properties of newly introduced wires
      can be considered for its application in both details friction and frictionless
      mechanics in retraction phase of fixed orthodontic treatment.

PMID- 29652018
TI  - Restricted mouth opening and its definitive management: A literature review.
AB  - Purpose: This review was intended to discuss the various possible modifications
      suggested in the literature for prosthetic steps and surgical corrective
      procedures in nonresponding or complicated cases during rehabilitation of
      patients with restricted mouth opening. Material and Methods:: Medline, PubMed,
      and Google were searched electronically for articles using keywords: microstomia
      and treatment options for restricted mouth opening. The various articles on
      prosthodontic rehabilitation in microstomia were segregated. From these, various
      modifications in the prosthetic steps were reviewed. Results:: Oral hygiene
      maintenance is difficult for patient either due to limited access or due to
      associated lack of manual dexterity, so dental decay and periodontal problems are
      more extensive in such patients; hence, tooth loss is a common finding. All
      prosthetic procedures require wide mouth opening to carry out various steps,
      starting from tray placement during impression making to the final prosthesis
      insertion, especially removable prosthesis. Various prosthetic modifications
      given by authors are included in this review for each step in prosthodontic
      management. A total of eight stock tray designs, 12 custom tray designs, and 17
      removable prosthesis designs are discussed along with fixed (either tooth
      supported or implant-supported) and maxillofacial prosthesis. However, some
      patients require surgical intervention also for the correction of microstomia
      either for function or for esthetic purpose before prosthetic rehabilitation and
      are also enumerated here. Conclusion: Among all prosthetic restorative options,
      removable prosthesis is most difficult for dentist to fabricate as conventional
      methods are either very difficult or impossible to apply. To get a more accurate
      final prosthesis, we need to modify these steps according to the existing case.
      Several modifications available are discussed here which can help while managing
      these patients.

PMID- 29652019
TI  - Efficacy of green tea-based mouthwashes on dental plaque and gingival
      inflammation: A systematic review and meta-analysis.
AB  - Objectives: The purpose of this study was to conduct a systematic review and if
      appropriate a meta-analysis of the efficacy of daily rinsing with green tea-based
      mouthwashes in terms of plaque index (PI) and/or gingival index (GI) as compared
      to other mouthwashes in plaque-induced gingivitis patients. Materials and
      Methods: MEDLINE, Cochrane Central Register of Controlled Trials, IndMed, Google
      Scholar, and major journals were searched for studies up to December 2016. A
      comprehensive search strategy was designed, and the eligible articles were
      independently screened for eligibility by two reviewers. Randomized controlled
      trials in which individuals were intervened with oral mouthwashes of interest
      were included. Where appropriate, a meta-analysis was performed and standardized
      mean differences (SMDs) for GI and PI were calculated. Results: A total of 9
      articles out of the 311 titles met the eligibility criteria. A meta-analysis was
      performed for five studies that compared green tea-based mouthwashes with
      chlorhexidine (CHX). The SMD for PI was -0.14 (95% CI: -1.70, 1.43; P = 0.86 and
      I2 = 94%), while that for GI was 0.43 ((95% CI: -0.63, 1.49; P = 0.43, I2 = 89%).
      Both these estimates suffered from significant heterogeneity. For both PI and GI,
      two studies were in favor of green tea while three studies were in favor of CHX.
      Conclusions: Green tea-based mouthwashes can be considered an alternative to CHX
      mouthwashes in sustaining oral hygiene, especially because of the added
      advantages provided by such herbal preparations.

PMID- 29652020
TI  - Classification systems for gingival recession and suggestion of a new
      classification system.
AB  - Background: Gingival recession is one of the most usual esthetic concerns
      associated with the periodontal tissues. Classification of such condition is
      important to diagnose, determine the prognosis, and frame the treatment plan.
      Various classifications have been put forward since decades to classify gingival
      recession. Miller's classification is the widely used classification among all
      classifications, but certain drawbacks have been noted in this classification.
      Therefore, an effort is made to review most commonly used classification systems
      for gingival recession, and their drawbacks further come up with a proposal of
      new classification system for gingival recession.

PMID- 29652021
TI  - An unusual presentation of ghost cell odontogenic carcinoma: A case report with
      review of literature.
AB  - Ghost cell odontogenic carcinoma (GCOC) is a malignant odontogenic epithelial
      tumor which is an exceedingly rare, highly aggressive, rapidly growing, and
      infiltrative tumor forming the malignant counterpart of long-standing benign
      cystic lesions coming in the spectrum of calcifying odontogenic cysts. To date,
      only a few cases have been reported in the medical literature. A case of unusual
      presentation of GCOC is presented and the clinical, histopathological, and
      immunohistochemical features are discussed along with a literature review. Our
      case report further emphasizes the bizarre biological behavior of this tumor and
      the need for strict long-term surveillance of the patients as metastasis to
      distant sites has been reported.

PMID- 29652022
TI  - Permanent mandibular protostylid: A rare developmental anomaly and its overview.
AB  - Developmental malformations of the teeth might result in alterations of their
      size, shape, and structure. An accessory cusp is a developmental alteration to
      the shape of the teeth and is more commonly found in anterior teeth, and its
      occurrence in permanent molars is quite rare. Accessory cusps occurring in
      permanent mandibular molars are termed as protostylids. Although they do not pose
      any significant problem with respect to the function and occlusion, it is of
      tremendous importance in forensic odontology. This case report presents a rare
      finding of protostylid on the permanent mandibular molar, and its clinical
      implications are illustrated.

PMID- 29652023
TI  - Actinomycotic osteomyelitis of palate masquerading periapical pathology: A rare
      case report.
AB  - Osteomyelitis is an infection that is challenging to manage due to the poor
      vascularization of bone that favors the proliferation of microorganisms. We
      report a case of osteomyelitis occurring in endodontically treated teeth in the
      maxillary palatal region. Clinically and radiographically, it was initially
      diagnosed as osteomyelitis and was treated accordingly with antibiotics for 1
      year with no reported healing. Later, biopsy was done and the findings were
      consistent with that of chronic osteomyelitis in association with infection by
      Actinomyces organisms. Thus, the case highlights the rare occurrence of
      actinomycotic osteomyelitis in maxilla and the importance of biopsy and
      histopathology which will help in correct diagnosis and rapid resolution through
      appropriate antibiotic therapy.

PMID- 29652024
TI  - Intra-alveolar extraction of impacted distoangular mandibular third molars: A
      novel technique.
AB  - Recent trends in maxillofacial surgery are to reduce the trauma to the adjacent
      soft tissue. The distoangular impaction presents a challenge to the maxillofacial
      surgeon and also results in more surgical morbidity. Here, we present a minimally
      invasive extraction technique for the distoangular mandibular third molar
      impaction.

PMID- 29652025
TI  - Chronic periodontitis prevalence and the inflammatory burden in a sample
      population from South India.
AB  - Context: Periodontal diseases are among the most prevalent oral diseases in the
      world. Apart from repercussions in the oral cavity, there is evidence that
      periodontitis contributes to systemic damage in chronic diseases such as
      cardiovascular disease, diabetes, and preterm low birth weight. Aims:: The aims
      of this study were to estimate the prevalence of chronic periodontitis in a
      sample urban population (<18 years) in Tamil Nadu and to estimate the
      inflammatory burden posed by chronic periodontitis by calculating the periodontal
      inflammatory surface area. Settings and Design:: This was a population-based
      study and cross-sectional design. Subjects and Methods:: A total of 1000
      individuals (<18 years) were selected and screened for their periodontal status,
      oral hygiene status (OHI), and the periodontal inflamed surface area (PISA) in an
      outreach center located in Chennai, India. Statistical Analysis Used:: The
      proportion of individuals with different periodontal states (health, gingivitis,
      and periodontitis) was determined. A multivariate logistic regression analysis
      was performed to assess the influence of the individual risk factors such as
      habits (tobacco use), systemic conditions (diabetes), and oral hygiene
      maintenance on periodontitis prevalence in the sample population. Results:: A
      high prevalence of periodontal disease was observed in the study population
      (42.3%). Among the urban participants, age, cigarette smoking, pan chewing,
      decayed, missing, and filled teeth scores, OHI scores, and PISA scores were found
      to be significantly associated with periodontitis (P < 0.05). Conclusions::
      Periodontitis prevalence appears to be high even in areas with adequate access to
      oral health care and an inflammatory burden risk exists in a definitive manner.

PMID- 29652026
TI  - Preoperative biliary drainage using a fully covered self-expandable metallic
      stent for pancreatic head cancer: A prospective feasibility study.
AB  - Background/Aims: The role of endoscopic preoperative biliary drainage (PBD) for
      pancreatic head cancer is controversial because of the high incidence of stent
      occlusion before surgery. This study was performed to evaluate the feasibility
      and safety of PBD using a fully covered self-expandable metallic stent (FCSEMS).
      Patients and Methods: This multicenter prospective study involved 26 patients
      treated for pancreatic head cancer with distal bile duct obstruction from April
      2011 to March 2013. An FCSEMS was endoscopically placed in 24 patients. Among
      these, 7 patients were diagnosed with unresectable cancer, and 17 underwent
      surgery at a median of 18 days after FCSEMS placement. The main outcome measure
      was preoperative and postoperative adverse events. Results: Two adverse events
      (cholecystitis and insufficient resolution of jaundice) occurred between FCSEMS
      placement and surgery (12%). Postoperative adverse events occurred in eight
      patients (47%). The cumulative incidence of stent-related adverse events 4 and 8
      weeks after FCSEMS placement among the 24 patients who underwent this procedure
      were 19%. Conclusions: PBD using an FCSEMS is feasible in patients with
      resectable pancreatic head cancer. Placement of an FCSEMS can be an alternative
      PBD technique when surgery without delay is impossible. A larger randomized
      controlled trial is warranted.

PMID- 29652027
TI  - Pokeweed antiviral protein attenuates liver fibrosis in mice through regulating
      Wnt/Jnk mediated glucose metabolism.
AB  - Background/Aims: Pokeweed antiviral protein (PAP) has been reported to
      downregulate Wnt/Jnk pathway and attenuate liver fibrosis. This study was
      designed to intensively explore the mechanism of anti-fibrosis effect of PAP.
      Materials and Methods: Hepatic stellate cell (HSC) activation was induced by high
      concentration of glucose. Cell viability was detected at different time points
      after PAP treatment. Meanwhile, hepatic fibrosis models in mice were induced by
      CCl4 injection. In the end, liver pathology was observed and contents of alanine
      transaminase, aspartate transaminase, lactic dehydrogenase, hyaluronic acid (HA),
      and laminin (LN) in serum together with hydroxyproline (Hyp) in liver were
      measured. The mRNA and protein expressions of HK2, PFKP, PCK1, and FBP1 as well
      as Jnk expression in HSC-T6 cells and liver tissue were detected by qPCR and
      western-blot, respectively. Results: Compared with high glucose, PAP reduced
      viability and expressions of HK2, PFKP, alpha-SMA, and Col1A1, where as enhanced
      the expressions of PCK1 and FBP1 in HSC-T6 cells (P < 0.05) respectively. PAP
      attenuated liver pathology, improved liver function, and reduced collagen
      deposition in liver tissue compared with the model group (P < 0.05) respectively.
      Moreover, PAP reduced expressions of HK2, PFKP, alpha-SMA, and Col1A1 where as
      increased the expression of PCK1 and FBP1 in the liver of mice compared with the
      model group (P < 0.05) respectively. Most importantly, PAP reduced the
      phosphorylation of Jnk both in cells and liver tissue compared with the model
      group (P < 0.05) respectively. Conclusions: Our results demonstrated that PAP
      attenuated liver fibrosis by regulating Wnt/Jnk-mediated glucose metabolism. It
      provided us a new target for the treatment of liver fibrosis.

PMID- 29652028
TI  - Risk factors of in-hospital mortality among patients with upper gastrointestinal
      bleeding and acute myocardial infarction.
AB  - Background/Aims: Patients with simultaneous upper gastrointestinal bleeding
      (UGIB) and acute myocardial infarction (AMI) have higher mortality than patients
      with either GIB or AMI. We aimed to assess the incidence and risk factors of in
      hospital mortality in patients with UGIB and AMI. Patients and Methods: A total
      of 243 patients with UGIB and AMI were enrolled during 2012-2017. Clinical and
      laboratory data were collected and analyzed for clinical characteristics and
      potential risk factors of in-hospital mortality. Results: Among the 243 patients,
      60 in-hospital deaths were observed (in-hospital mortality rate of 24.7%).
      Patients who died were older than the survivors (78.7 +/- 6.6 vs. 72.6 +/- 10.5
      years, P < 0.001). Compared with survivors, patients who died showed increased
      peak white blood cell (WBC) count (9.74 +/- 4.72 vs. 7.60 +/- 2.91 * 109/L, P=
      0.002), serum creatinine levels [134 (106, 190) vs. 97 (79, 125) mmol/L, P=
      0.014], peak blood urine nitrogen levels (16.31 +/- 8.48 mmol/L vs. 9.86 +/- 6.33
      mmol/L, P < 0.001), and peak brain natriuretic peptide (BNP) amounts [13,250
      (6071, 30,000) vs. 3598 (728, 12,842) pg/mL, P < 0.001]. Meanwhile, patients who
      died also displayed lower minimum hemoglobin levels (78.3 +/- 21.1 vs. 86.3 +/-
      22.3 g/L, P= 0.018) and minimum platelet counts (184.3 +/- 79.1 vs. 214.6 +/-
      80.1 * 109/L, P= 0.013). In multivariable logistic analysis, age [OR (95% CI)
      =1.118 (1.053-1.186), P < 0.001], peak WBC count [OR (95% CI) =1.252 (1.113
      1.407), P < 0.001], minimum platelet count [OR (95% CI) = 0.994 (0.989-1.000), P=
      0.032], and peak BNP levels [OR (95% CI) =3.880 (1.761-8.550), P= 0.001] were
      independent predictors of in-hospital mortality. Conclusions: Patients with UGIB
      and AMI had a high in-hospital mortality, which was independently associated with
      age, peak WBC count, minimum platelet count, and peak BNP levels.

PMID- 29652030
TI  - Endoscopic ultrasound-guided gallbladder drainage: Results of long-term follow
      up.
AB  - Background/Aim: Recently, endoscopic ultrasound-guided gallbladder drainage (EUS
      GBD) has emerged using a self-expandable metallic stent (SEMS). The aim of the
      study was to evaluate the long-term outcomes of this procedure. In addition, the
      efficacy and safety of EUS-GBD with SEMS were assessed. Patients and Methods:
      Thirteen consecutive patients who underwent EUS-GBD for acute cholecystitis
      between February 2014 and September 2016 were included in this retrospective
      study. EUS-GBD was performed under the guidance of EUS and fluoroscopy, through
      puncturing the gallbladder with a needle, inserting a guidewire, dilating the
      puncture hole, and placing a SEMS. Results: The rates of technical success,
      functional success, and adverse events were 100%, 92.3% and 7.7%, respectively.
      The median procedure time was 26.9 min (range 19-42 min). The median follow-up
      time was 240 days (range 14-945 days) and during this follow-up period recurrence
      of cholecystitis was observed in one patient (7.7%). Conclusion: EUS-GBD with a
      SEMS is a possible alternative treatment for acute cholecystitis in high surgical
      risk patients. Long-term outcomes after EUS-GBD were promising.

PMID- 29652029
TI  - Evaluation of a modified rat model for functional dyspepsia.
AB  - Background/Aim: The purpose of this study was to establish a modified rat model
      with functional dyspepsia (FD) and analyze the changes in gastrointestinal
      motility and brain-gut peptide levels in serum and brain-gut axis. Materials and
      Methods: Male Wistar rats were divided into control group (Con) and FD model
      group. FD model was established by stimulating semi-starvation rats via tail
      damping, provocation, and forced exercise fatigue until gastrointestinal motility
      disorder appeared, and then levels of motilin, leptin, cholecystokinin (CCK), and
      vasoactive intestinal peptide (VIP) were detected in serum by enzyme linked
      immunosorbent assay and in duodenum, antrum, and hypothalamus by
      immunohistochemistry, reverse transcriptase-polymerase chain reaction, and
      Western blot. Results: The results showed rates of intestinal propulsion and
      gastric emptying slowed down markedly compared to Con (P < 0.05), the
      gastrointestinal electric activity attenuated, and migrating motor complex (MMC)
      interrupted in the model group. The levels of leptin and VIP markedly increased,
      but motilin decreased as compared to the Con (P < 0.05) in serum and in the above
      tissues. It is interesting that the level of CCK decreased in the antrum and
      duodenum but increased in the hypothalamus as compared to Con (P < 0.05).
      Conclusions: The modified rat model meets the diagnostic criteria of FD and can
      be used as a method for studying FD in animals.

PMID- 29652031
TI  - Association between patient characteristics and magnetically controlled capsule
      endoscopy findings.
AB  - Background/Aim: Magnetically-controlled capsule endoscopy (MCE) is a potential
      option for the evaluation of gastric diseases in cases that are unsuited for
      conventional endoscopy, avoiding discomfort, sedation, and related complications.
      This retrospective study investigated associations between MCE findings and
      patient gender, age, and inpatient/outpatient status. Patients and Methods: The
      data of 580 consecutive patients who underwent MCE from 2015 to 2016 were
      analyzed. Data included age, gender, indication for MCE, inpatient/outpatient
      status, overall coverage of gastric anatomical landmarks, and comorbid
      conditions. Results: Compared with outpatients, inpatients had a higher rate of
      overall significant MCE findings (P = 0.014), polyp (P = 0.03), and ulceration (P
      = 0.003). MCE findings of the inpatient men and women were similar. Considering
      all patients, the percentage with ulceration was significantly higher in men than
      in women (P = 0.004), and men were younger (P < 0.001). Compared with younger
      patients, those aged >=60 years had significantly higher rates of overall
      significant findings, mainly polyp and angiodysplasia. Conclusions: Compared with
      outpatients, the inpatients showed higher overall significant findings. Men
      undergoing MCE were younger than the women, and more likely to have ulcerations.
      Older patients, whether outpatient or inpatient, had higher rates of significant
      findings, mainly polyp and angiodysplasia.

PMID- 29652032
TI  - Prevalence and clinical predictors of LPR among patients diagnosed with GERD
      according to the reflux symptom index questionnaire.
AB  - Background/Aims: Gastroesophageal reflux disease (GERD) is a common condition
      that can lead to significant morbidity. Laryngopharyngeal reflux (LPR) is a
      distinct clinical entity that can occur simultaneously with GERD, necessitating
      additional treatment measures. The degree of overlap and clinical predictors of
      LPR among patients with GERD remains unknown. We aim to measure the prevalence of
      LPR in patients with GERD and identify clinical predictors. Patients and Methods:
      We performed a cross-sectional study involving patients with confirmed GERD
      according to the GERD questionnaire (GerdQ) using the reflux symptom index (RSI).
      Data on demographics, comorbidities, past and current medications, and GERD
      related lifestyle measures were documented. The prevalence of LPR was calculated.
      Linear and logistic regression analyses were conducted to correlate GerdQ and
      RSI, and to identify clinical predictors of LPR, respectively. Results: A total
      of 80 patients with confirmed GERD were consecutively recruited and surveyed.
      Mean age was 43 (+/-16) and 60% were females. The majority of patients were
      Saudis (51%) and only 24% were smokers. The mean duration of GERD was 7 (+/-4.4)
      years and the average body mass index (BMI) was 36 +/- 22. Sixty-six percent of
      the patients consumed coffee on regular basis. On simple and multiple linear
      regression analyses, a strong, positive correlation was observed between the
      GerdQ and RSI scores (coefficient = 1.13, 95%CI = 0.39-1.86), and ipratropium
      bromide inhaler was positively associated with RSI scores (coefficient = 13.12,
      95%CI = 0.16-26.09). LPR was identified in 57 patients (71%). On simple and
      multiple logistic regression analyses, GerdQ scores (OR = 1.78, 95%CI = 1.13
      2.80), BMI (OR = 1.07, 95%CI = 1.01-1.14), duration of GERD in years (OR = 1.42,
      95%CI = 1.04-1.93), and the type of gender (OR = 49.67, 95%CI = 1.32-1870)
      appeared to increase the risk of LPR, whereas coffee consumption (OR = 0.0005,
      95%CI = 1.82e-06, 0.13) appeared to be negatively associated with LPR.
      Conclusions: Contradictory to what is frequently reported, LPR commonly occurs
      and positively correlates with GERD. Several modifiable clinical predictors of
      LPR might exist, which highlight the importance of performing a complete clinical
      assessment of the patients with reflux symptoms.

PMID- 29652033
TI  - The effect of virulence genotypes of Helicobacter pylori on eradication therapy
      in children.
AB  - Background/Aim: It is important to eradicate Helicobacter pylori at an early
      stage in patients during childhood to potentially prevent the development of H.
      pylori-related diseases. Studies have demonstrated that the virulence genotype of
      H. pylori influences the efficacy of eradication therapy. The efficacy of triple
      therapy has decreased significantly, which has seriously affected the clinical
      outcome of children with H. pylori infection. In this study we aimed to
      investigate the influence of virulence genotypes of H. pylori on triple
      eradication therapy in children. Patients and Methods: H. pylori strains were
      isolated from the gastric antrum mucosa in children with upper gastrointestinal
      symptoms. Polymerase chain reaction (PCR) was conducted to determine the H.
      pylori cagA, vacA, and iceA genotypes. All patients with H. pylori infection were
      administered 14-day triple therapy. After drug withdrawal for at least 4 weeks,
      the 13C-urea breath test (13C-UBT) was used to observe the therapeutic effect of
      H. pylori eradication. The eradication rates were evaluated by intention-to-treat
      (ITT) and per-protocol (PP) analyses. Results: A total of 107 patients were
      enrolled in this study. Nine patients were lost to follow-up, and 98 patients
      were administered eradication therapy. Based on ITT and PP analyses, the H.
      pylori eradication rate was 64.5% (69/107) and 70.4% (69/98), respectively. Among
      the successful eradication groups, the cagA-positive, vacA s1a, vacA s1c, vacA
      m1, vacA m2, iceA 1, and iceA 2 genes were identified in 72.8%, 68.1%, 76.9%,
      60.0%, 74.6%, 71.8%, and 75.0% of strains, respectively. Of the unsuccessful
      eradication groups, the cagA-positive, vacA s1a, vacA s1c, vacA m1, vacA m2, iceA
      1, and iceA 2 genes were identified in 27.2%, 31.9%, 23.1%, 40.0%, 25.4%, 28.2%,
      and 25.0% of strains, respectively. No statistically significant differences were
      noted in the detection rate of the H. pylori genotypes between the H. pylori
      successful and unsuccessful eradication groups (P > 0.05). Conclusions: The cagA,
      vacA, and iceA genotypes of H. pylori are not associated with the efficacy of
      omeprazole-based triple therapy on the eradication of H. pylori infection in
      children.

PMID- 29652035
TI  - Preoperative biliary drainage in pancreatic head cancer patients.

PMID- 29652034
TI  - Prevalence of sleep disorder in irritable bowel syndrome: A systematic review
      with meta-analysis.
AB  - Background/Aims: We conducted this meta-analysis to evaluate the prevalence of
      sleep disorder in irritable bowel syndrome (IBS) patients and study the
      association between IBS and sleep disorder. Materials and Methods: A systematic
      search was conducted by searching PubMed, Embase, and Cochrane library databases
      using the following search terms: "functional gastrointestinal disorders," "Sleep
      disturbance," "Sleep disorder," "insomnia," "Dysomnias," "irritable bowel
      syndrome," and "IBS." Studies evaluating the association between IBS and sleep
      disorder were identified. Data analysis was conducted using meta-analysis
      software Comprehensive Meta-Analysis (CMA) 2.0. Heterogeneity across studies was
      evaluated by chi2and I2statistics. Publication bias was evaluated by funnel plot,
      Begg's test, and Egger's test. Sensitivity analysis was also performed by
      removing each single study separately. Results: The bibliographical search
      yielded a total of 2866 studies. Finally, 36 studies including 63620 participants
      were identified. The prevalence of sleep disorder in IBS was 37.6% (95% CI: 31.4%
      to 44.3%) based on this meta-analysis. The pooled odds ratio was 2.618 (95% CI:
      2.052% to 3.341). Publication bias was not determined. Regarding the sensitivity
      analysis, the outcome was stable regardless of which study was removed.
      Conclusions: The prevalence of sleep disorder was higher in IBS compared to
      healthy controls and may be associated with the pathogenesis of IBS. The
      prevalence of sleep disorder in IBS may differ according to different areas, age,
      gender, occupation, and IBS diagnostic criteria. Further studies are needed to
      investigate any possible causal relationship between sleep disorder and IBS.

PMID- 29652037
TI  - Warning for cardiologists: alcohol is not suitable for cardiovascular prevention.

PMID- 29652036
TI  - Clinical Effects of "Selective Drug" Regulating Vagus Nerve Signal Pathway in
      Vagally-Mediated Atrial Fibrillation.
AB  - BACKGROUND The cardiac autonomic nervous system plays a crucial role in genesis
      and development of atrial fibrillation (AF) through the G protein signal
      transduction pathway. Therefore, intervening in the G protein signal transduction
      pathway may be a new "selective drug" method to regulate autonomic nerve activity
      to prevent vagally-mediated AF. MATERIAL AND METHODS Seventeen adult beagles were
      randomized into 3 groups: shame-operation control group (group A, n=5), empty
      vector gene control group (group B, n=6), and Galphai2ctp gene experimental group
      (group C, n=6). Group A was injected with normal saline into the anterior atrial
      wall, and group B and group C animals were injected with recombinant adenovirus
      with empty vector or Galphai2ctp vector in the same region. AF was induced by the
      method of rapid atrial pacing in groups B and C. To determine the clinical effect
      of vagal modulation, the effective refractory periods (ERP) and field action
      potential duration (FAPD) were evaluated by electrophysiological study. The
      expression levels of tyrosine hydroxylase (TH) and choline acetyl transferase
      (CHAT) in different parts were determined with immunohistochemistry. RESULTS
      After successful Gai2ctp gene transfer, in group B, the ERP and FAPD
      significantly decreased (P<0.05), and TH and CHAT expression observably increased
      (P<0.05), while those differences were absent between groups A and C (P>0.05).
      CONCLUSIONS Recombinant adenovirus-mediated overexpression of Galphai2ctp in
      canine myocardial cells can interfere with the activity of the vagus nerve,
      reverse the development and progression of electrical remodeling, and reduce the
      incidence of AF.

PMID- 29652038
TI  - Analysis of novel cardiovascular biomarkers in patients with peripheral artery
      disease (PAD).
AB  - BACKGROUND: Peripheral artery disease (PAD) is a common form of manifestation of
      atherosclerosis. PAD has a considerable impact on morbidity, hospitalisation
      rates and health- care costs. Biomarkers have been introduced in many
      cardiovascular disease entities over the last years. However, an analysis on the
      correlation of biomarker levels and PAD is still lacking. METHODS: A total of 106
      patients were enrolled in this current study, 51 that were diagnosed with PAD and
      55 with excluded coronary and peripheral artery disease as controls. During
      outpatient visits, plasma samples of all patients were obtained and analyzed for
      sST2 (hemodynamics and inflammation), Galectin-3 (fibrosis and remodeling), GDF
      15 (remodeling and inflammation), suPAR (inflammation), and Fetuin-A (vascular
      calcification) by use of ELISA after informed consent. RESULTS: Compared with
      controls, patients with PAD showed significantly higher levels of sST2 (5248 vs.
      7503 pg/ml, p<0.001), suPAR (2267 vs. 2414 pg/ml, p=0.02), Galectin-3 (2795 vs.
      4494 pg/ml, p<0.001), and GDF-15 (549 vs. 767 pg/ml, p<0.001). Fetuin-A showed a
      trend towards lower levels in patients with PAD (117 vs. 100 ng/ml, p=0.119).
      CONCLUSIONS: Circulating levels of sST2, suPAR, Galectin-3, and GDF-15 were
      significantly elevated in PAD patients. In contrast, Fetuin-A levels showed a
      decrease in PAD patients indicating increased vascular calcification. Thus, by
      incorporating different pathophysiological processes present in PAD, tested novel
      biomarkers facilitate a more precise diagnosis as well as a more accurate
      evaluation of disease severity and progression.

PMID- 29652039
TI  - Changes in interleukin-10 and apoptotic genes in rats with myocardial.

PMID- 29652040
TI  - [The physical and chemical properties of the skin and the action of therapeutic
      physical factors].
AB  - This article discusses the importance of the physical and chemical properties of
      the skin subjected to the action of the therapeutic physical factors. The author
      presents the data illustrating the influence of alterations in skin permeability
      on the penetration of medicinal substances into the organs and tissues of the
      body under conditions of application of various physico-pharmacological methods
      based on the use of chemical ingredients of peloid therapy and other
      balneotherapeutic technologies. The effectiveness of skin permeability is known
      to be of special importance in the context of physical therapy since it
      determines the action of its individual components. The influence of skin pH
      values as the parameters determining the peculiar features of percutaneous
      electrophoresis of cations and anions is demonstrated. It is shown that the
      reduction of electrical resistance of the skin barrier significantly improves the
      electrophoretic propagation of medicinal substances; therefore, such alteration
      determines, in many respects, the choice of the dosimetric parameters for
      electropuncture and electro acupuncture. Special attention is given to the
      discussion of the opportunities through which the variation of the skin optical
      properties could be applied to enhance the efficiency of phototherapy. The need
      to continue research on this problem topical for physiotherapy is emphasized.

PMID- 29652041
TI  - [Alternating pneumocompression - effective physiotherapeutic method for the
      prevention of venous thromboembolic complications in patients of medium and high
      risk in the acute period of the stroke].
AB  - BACKGROUND: the patients presenting with severe post-stroke in the acute period
      of this condition are characterized by the high risk of venous thromboembolic
      complications (VTEC), with the most dangerous of them being pulmonary embolism
      that makes an appreciable contribution to the mortality rate of such patients at
      the hospital stage of their treatment. Among the physical methods for the
      prevention of VTE, such as wearing graduated compression stockings (GCS),
      myoelectrostimulation (MES), pneumatic intermittent compression (PIC), only the
      latter technique has been shown to be efficient when applied for the treatment of
      surgical patients during the post-stroke period with the level of evidence 2B and
      the very uncertain parameters of the impact. AIM: The objective of the present
      study was to evaluate the advantages of the PIC in comparison with that of GCS
      and MES, substantiate the choice of the former method for the management of the
      high-risk post-stroke patients, and determine the impact parameters of PIC during
      the peracute and acute periods of the disease. MATERIAL AND METHODS: We conducted
      a series of analyses of the results of several controlled randomized studies and
      relevant reviews of the literature with a view to determining the feasibility and
      effectiveness of application of one or another approach and clarifying the
      parameters of the exposure to GCS, MES, and PIC for the prevention of VTEC.
      RESULTS AND DISCUSSION: The results of these studies gave evidence that the
      effectiveness of the GCS and MES is insufficient in contrast to that of PIC that
      was found to decrease the relative risk of deep vein thrombosis (DVT) by 62%
      compared with placebo and by 47% in comparison with GCS. The low risk of DVT
      associated with the application of PIC was apparent from the low OR value of 0.45
      and the absolute reduction in the risk of DVT by 3.6%. The analysis of the
      parameters being used made it possible to identify side effects and thereby
      allowed to formulate the optimal method for the application of PIC for the
      purpose of prevention of VTEC in the post-stroke patients during the peracute and
      acute periods of the disease. CONCLUSION: Only PIC of all the currently available
      methods for the physical prevention of VTEC in the group of high risk post-stroke
      patients during the peracute and acute periods of this condition can be practiced
      in the reliable evidence-based manner. The most rational PIC modality consists of
      exerting the external pressure on the lower extremities within the first 12-24
      hours after stroke with the use of the cuffs of the "lower leg" type (i.e. at a
      pressure of 40-50 mm Hg in the wave mode with memorization for the multi
      sectional cuffs, daily in the continuous manner throughout the daytime till the
      patient is downgraded to the group at lower risk of VTEC or actually till the
      discharge from the hospital.

PMID- 29652042
TI  - [Motor learning of the post-stroke patients presenting with upper limb paresis on
      the mechanotherapeutic system].
AB  - BACKGROUND: the relevance of this study arises from the high prevalence of upper
      limb motor impairment and pathological synergy in the post-stroke patients; these
      conditions are very difficult to correct with the use of the traditional
      rehabilitation methods. A promising but insufficiently studied approaches are the
      virtual reality (VR) technology as well as its combination with other techniques.
      AIM: The objective of the present study was to evaluate the influence of the
      training making use of the mechanotherapeutic system on the motor function of the
      paretic hand. MATERIAL AND METHODS: A total of 30 patients were enrolled in this
      study. The main group comprised 20 of them who completed the training course on
      the mechanotherapeutic system allowing for separate adjustment of weight support
      for the shoulder and the forearm, VR feedback with individual setting of the
      active working space, and augmented functional exercises. The control group
      consisted of the patients (n=10) who performed the task-oriented motor training
      course of an equal duration with arm weight support and visual feedback. RESULTS
      AND DISCUSSION: The assessment based on the Fugl-Meyer scale (FMA) showed the
      statistically significant changes in the passive motion range in the patients of
      both groups, but only those comprising the main group were found to experience
      the improvement of the major movements of the arm, wrist, and hand as well as
      movements outside synergy (p<0.005). Fine motor skills estimated from the results
      of the Action Research Arm test (ARAT) improved only in the main group due to the
      cylindrical and pinch grip (p<0.005). Also, only patients of the main group,
      improved daily living skills evaluated based on the Frenchay Arm test (FAT)
      (p<0.005). CONCLUSION: The results of the present study give evidence that the
      use of combined training with arm weight support and VR feedback contributes to a
      more complete recovery of motor and daily living skills in the upper limb of post
      stroke patients, compared to the classical task-oriented training with visual
      feedback.

PMID- 29652043
TI  - [The hardware techniques for the restoration of the gait stereotype in the
      patients following total hip replacement: the personalized approach].
AB  - BACKGROUND: total hip replacement has long ago become the "golden standard" for
      the treatment of dysplastic coxarthrosis in thousands of the patients receiving
      it every year. In the meantime, the analysis of the specialized literature gives
      evidence of the lack of a systematic and personified approach to the
      rehabilitation treatment. AIM: The objective of the present study was to improve
      medical rehabilitation of the patients following the total hip replacement and to
      develop the personalized programs for walking modality reconstruction taking into
      consideration the age and the body weight of the patients. PATIENTS AND METHODS:
      A total of 240 patients were available for the observation including 184 women
      and 56 men. They were divided into three study groups and one control group, with
      the differentiation into the following three subgroups: one comprised of the
      patients of moderate acerage age and body weight, the other containing the obese
      patients (BMI>35), and the third one involving the elderly patients (age >70
      years); each subgroup consisted of 20 patients. All the patients received the
      early basic rehabilitation treatment, those in the study groups had to perform in
      addition the robotic training based on the use of hardware techniques
      supplemented by passive mechanotherapy and electromyostimulation designed to
      restore the walking stereotype with three types of devices: body weight
      unloading, video-reconstruction associated with biological feedback and
      robototherapy. RESULTS: The comparative analysis of the effectiveness of various
      methods of gait reconstruction has demonstrated the high effectiveness of the
      application of the hardware technique in the patients of moderate acerage age and
      body weight. At the same time, the elderly patients had a significantly higher
      rate of successful walking reconstruction efficiency under the influence of the
      video-associated training with biological feedback (3 times that achieved with
      training using the device for unloading the body weight and 4 times compared with
      the result of a course of robotic walk. The evaluation of the application of the
      techniques for the gait stereotype reconstruction in the obese patients gave
      evidence of the advantage of the Lokomat robotic trainings that produced 6 times
      better results than unloading of the body weight and 5 times better ones than the
      video-associated training with biological feedback. DISCUSSION: The results of
      the present study are on the whole comparable with the data reported by other
      authors although its design was different from that of the majority of the
      published studies in that our patients were allocated to different subgroups for
      the further personalization of the methods applied to restore the gait
      stereotype. The factors limiting the use of the results of this study include the
      medium-high level of the patients' welfare most of whom are residents of the city
      of Moscow and Moscow region characterized by a relatively high quality and
      accessibility of health care. It means that the results of such studies as the
      one described in the present article are directly related to the quality and
      accessibility of health care and can be extrapolated only to the socially safe
      and well-to-do patients. CONCLUSIONS: All the hardware techniques are equally
      effective in the patients of moderate average age and body weight. The elderly
      patients showed the best results using the video-reconstruction associated with
      biological feedback, while the Locomat technique was especially useful for the
      obese patients.

PMID- 29652044
TI  - [The ultrastructure of Sertoli cells and spermatogonia in the rats exposed to
      radiation under conditions of therapeutic and prophylactic application of low
      intensity electromagnetic emission].
AB  - BACKGROUND: it has been demonstrated in various experimental studies that
      radiation exposure produces a negative impact on the processes of spermatogenesis
      associated with the disturbances of the microcirculation processes in the testes
      and the development of cellular and intracellular disintegration expressed as
      destructive changes in the cells leading to their death. AIM: The objective of
      the present study was to detect the ultrastructural abnormalities in the cells of
      Sertoli and spermatogonia under conditions of their exposure to radiation and to
      identify the peculiarities of their regeneration under the influence of the
      therapeutic and prophylactic application of low-intensity ultra-high frequency
      (UHF) electromagnetic radiation (EMR) and low-intensity low-frequency magnetic
      field (MF). MATERIAL AND METHODS: The experiments were carried out on 28 non
      pedigree mature male rats with the body weight 180-220 g that were divided into
      four groups. The first study group was comprised of the animals exposed to
      radiation followed by the application of low-intensity ultra-high frequency UHF
      electromagnetic radiation EMR. The rats in the second study group experienced
      effects of radiation and low-intensity low-frequency MF. The animals of the third
      (control) group were exposed to radiation alone, and those comprising the fourth
      group 1 (only radiation exposure) were considered to be intact. RESULTS: The
      studies with the use of electron microscopy showed that the therapeutic and
      prophylactic application of low-intensity ultra-high frequency (UHF)
      electromagnetic radiation and low-intensity low-frequency magnetic field caused
      the decrease in the number and the severity of post-radiation defects in the
      treated cells together with the increase of the number and size of mitochondria
      as well as hyperplasia of ribosomes; moreover, it promoted cellular and
      intracellular regeneration. UHF electromagnetic radiation had a more pronounced
      stimulating effect on the regeneration processes as compared with low-frequency
      MF. Particularly active processes of intracellular regeneration evolved in
      Sertoli cells; they were manifested as the increase in the number and size of
      mitochondria, enhanced hyperplasia of ribosomes, and formation of polysomes and
      new membranes of the granular endoplasmic reticulum. In spermatogonia,
      intracellular regeneration was less pronounced than in the Sertoli cells but was
      accompanied by enhanced cell regeneration and a greater number of reserve
      stem/progenitor cells. CONCLUSIONS: The results of the present study provide a
      rationale for the possibility of the application of a low-frequency magnetic
      field and especially UHF electromagnetic radiation for the further development of
      the promising therapeutic and preventive technologies with a view to their
      introduction into routine clinical practice dealing with radiation-induced
      pathology.

PMID- 29652045
TI  - [The medical-recreational and balneotherapeutic regions of the Krasnoyarsk
      Territory].
AB  - BACKGROUND: the creation of the efficient system of the spa and health resort
      based health care for the population of the entire territory of the Russian
      Federation requires the systematic evaluation and protection of the natural
      resources of country as a basis for the further development of the health resort
      and recreation facilities in different regions. AIM: The objective of the present
      study was to estimate the possibilities of expansion of the health resort and
      recreational activities based on the rational exploitation of the natural
      resources of the medical-recreational and balneotherapeutic areas of the
      Krasnoyarsk Territory. METHODS: The inspection of the medical-recreational and
      balneotherapeutic regions of the southern part of the Krasnoyarsk Territory with
      the evaluation of the medicinal and raw materials resources of the spa and health
      resort facilities located in this area. The comprehensive assessment of the
      landscape and climatic conditions of the territory was performed in compliance
      with the methodological recommendations No 96/226 "The bioclimatic passport of
      the medical-recreational and balneotherapeutic region" approved by the Ministry
      of Health of the Russian Federation as of 7 February 1997. The quality of water
      bodies/sources was carried out in conformity with the criteria envisaged by the
      methodological recommendations No 96/225 "Quality and safety control of mineral
      waters based on their chemical and microbiological characteristics" approved by
      the Ministry of Health of the Russian Federation as of 7 April 1997. Water typing
      was performed in accordance with GOST R 54316-2011 "Natural drinking mineral
      waters". RESULTS: The medical-recreational and balneotherapeutic regions in
      southern part of the Krasnoyarsk Territory are notable for the great variety of
      mountainous, forest and steppe landscape forms with their favorable bioclimatic
      conditions and unique resources of therapeutic muds and mineral carbonic waters.
      The area is characterized by the great potential for the further development of
      the climatic spa and health resort facilities, and the improvement of the health
      care service for both children's and adult populations based on the rational use
      of the local landscape and climatic factors available at the territories occupied
      by the spa and health resort facilities of the balneotherapeutic profile. The
      prospects for the further expansion of medical and recreational tourism are
      discussed. CONCLUSIONS: This article was designed to systematize the available
      data characterizing the balneotherapeutic and recreational conditions of the
      medical-recreational regions of the southern part of the Krasnoyarsk Territory
      with special reference to the value of their natural resources, such as
      bioclimate, mineral waters, therapeutic muds, etc., for their inclusion in the
      registry of the areas possessed of the great health-improving potential based on
      the rational nature use and environmental management programs.

PMID- 29652046
TI  - [Hydrogalvanic baths as a method of medical rehabilitation: a literature review
      and the prospects for the clinical application].
AB  - The hydrogalvanic baths provide a tool for the combined application of warm fresh
      water and low frequency electric current. These procedures are suitable for both
      systemic and local treatments. The mechanism behind their therapeutic action is
      based on synergistic effect of two therapeutic agents. This article presents the
      literature and historical review of the method as well as the current concept of
      hydrohalvanic therapy. The history of its development is associated with the
      improvement of the technical equipment and accumulation of clinical experience.
      Numerous studies carried out up to the present time have demonstrated that
      hydrohalvanic therapy can be effectively applied for the treatment of diabetic
      angiopathy, rheumatoid and gouty arthritis, fibromyalgia, ankylosing spondylitis.
      At the same time, the high potential of this method remains underestimated. At
      present, one of the most promising approaches to its clinical applications is the
      treatment of lumbosacral radiculopathy caused by degenerative vertebral disk
      lesions. The hydrogalvanic baths have analgesic, anti-inflammatory, and
      decongestant effects, improve microcirculation, and reduce sensory impairment. It
      is necessary to continue clinical investigations to obtain further evidence of
      the effectiveness of the method under consideration for the treatment of
      lumbosacral radiculopathy and to evaluate its short- and long-term effects. Their
      results will hopefully provide an opportunity to include the hydrogalvanic baths
      in the programs of medical rehabilitation of the patients presenting with
      lumbosacral radiculopathy.

PMID- 29652047
TI  - [Physical therapy of psoriasis. The modern methodological approaches].
AB  - This article describes the modern approaches to the application of physical
      factors for the treatment of various forms of psoriasis taking into consideration
      the severity of clinical manifestations and the phase of the disease, the extent
      of disturbances of the functional state of different organs. The principles of
      prescription of physiotherapeutictreatmnt are formulated taking account of the
      stages and forms of the disease. Special attention is paid to the high
      therapeutic effectiveness of ultraviolet irradiation of the skin including narrow
      band UVV (311 nm) as well as to photodynamic therapy (PUVA), intravenous laser
      irradiation of blood, and ozone therapy. Also considered is the spa and health
      resort-based treatment and peloid therapy at various stages of the pathological
      process. The application of the combined techniques is described with special
      reference to radon and hydrogen sulfide baths and microwave therapy in the
      patients presenting with psoriatic arthritis. Much attention is given to the
      effectiveness of the prescription of the spa and health resort-based treatment at
      the stationary and regressive stages of psoriasis. The pathogenetic mechanisms
      underlying the therapeutic action of the physical factors used for the treatment
      of patients suffering from psoriasis are discussed.

PMID- 29652048
TI  - [Should a doctor take into consideration the influence of climatic factors?
      Deliberations on the occasion of the publication of a new monograph (the book of
      essays of arid medicine by Z.R. Zununov, I.H. Nurov, and S.Z. Zununova)].
AB  - The authors analyze the monograph of the Uzbek scientists professor Z.R. Zununov,
      I.H. Nurov, and S.Z. Zununova "Essays of arid medicine" (Tashkent: "KAMALAK
      PRESS" publishing house, 2016;540). The book presents the results of the
      comprehensive bioclimatic assessment of the arid zones of Uzbekistan, their
      extreme climatic conditions (such as high intensity and solar radiation and the
      considerable duration of its period, dry air and summer heat, sandstorms (the so
      called "Afghans"), and the great variety of the natural health-improving factors
      including mineral waters, microclimate of the speleotherapeutic cave, the desert
      dune sand, etc. The work is based on the authors' conceptual theory of
      "arid/meteorological stress syndrome", underlain by the hypothesis of the
      predominant role of hyperthermal weather hypoxia. A wide range of issues id
      discussed related to weather and climate adaptation of the healthy subjects (both
      indigenous and non-indigenous residents) and the patients suffering from ischemic
      heart disease, chronic obstructive pulmonary disease, and rheumatoid arthritis.
      Of special interest are the methods proposed for the correction of dysadaptive
      changes including the application of the natural balneotherapeutic factors
      existing in the arid zone (hydrogen sulphide and iodine-bromine balneotherapy,
      climatic therapy, speleotherapy, and psammotherapy (arenation). An important
      definitive conclusion at which the authors arrive is the necessity of the
      experimental observations in agreement with the requirements of the medico
      biological ethics.

PMID- 29652049
TI  - [The Patriarch (in memory of prof. V.S. Ulashchik)].
AB  - The Patriarch (in memory of prof. V.S. Ulashchik).

PMID- 29652050
TI  - Long-term C. elegans immobilization enables high resolution developmental studies
      in vivo.
AB  - Live-imaging of C. elegans is essential for the study of conserved cellular
      pathways (e.g. EGFR/Wnt signaling) and morphogenesis in vivo. However, the
      usefulness of live imaging as a research tool has been severely limited by the
      need to immobilize worms prior to and during imaging. Conventionally,
      immobilization is achieved by employing both physical and chemical interventions.
      These are known to significantly affect many physiological processes, and thus
      limit our understanding of dynamic developmental processes. Herein we present a
      novel, easy-to-use microfluidic platform for the long-term immobilization of
      viable, normally developing C. elegans, compatible with image acquisition at high
      resolution, thereby overcoming the limitations associated with conventional worm
      immobilization. The capabilities of the platform are demonstrated through the
      continuous assessment of anchor cell (AC) invasion and distal tip cell (DTC)
      migration in larval C. elegans and germ cell apoptosis in adult C. elegans in
      vivo for the first time.

PMID- 29652051
TI  - Stable and oxidant responsive zwitterionic nanoclusters.
AB  - Zwitterions are promising ligands for the fabrication of non-toxic and non
      interacting biomaterials. Sulfonamide-based monothiol zwitterionic ligands on
      gold nanocluster (AuNC) surfaces provide nanomaterials with stable colloidal
      properties and intense red emission in biological environments. The fluorescence
      intensity of the nanocluster can be modulated by reactive oxygen species (e.g.
      OH), allowing for quantitative and selective sensing of antioxidants (e.g.
      ascorbic acid) in real time.

PMID- 29652052
TI  - Conformational control over an aldehyde fragment by selective vibrational
      excitation of interchangeable remote antennas.
AB  - We apply interchangeable vibrational antennas (OH or NH2 group) to achieve
      unprecedented conformational control over the heavy aldehyde fragment in 2-formyl
      2H-azirine. The two aldehyde conformers were manipulated bi-directionally, using
      selective vibrational excitation with narrowband near-infrared (NIR) light tuned
      at the wavenumbers corresponding to OH and NH2 stretching overtones and
      combination modes.

PMID- 29652053
TI  - The interplay of nanointerface curvature and calcium binding in weak
      polyelectrolyte-coated nanoparticles.
AB  - When engineering nanomaterials for application in biological systems, it is
      important to understand how multivalent ions, such as calcium, affect the
      structural and chemical properties of polymer-modified nanoconstructs. In this
      work, a recently developed molecular theory was employed to study the effect of
      surface curvature on the calcium-induced collapse of end-tethered weak
      polyelectrolytes. In particular, we focused on cylindrical and spherical
      nanoparticles coated with poly(acrylic acid) in the presence of different amounts
      of Ca2+ ions. We describe the structural changes that grafted polyelectrolytes
      undergo as a function of calcium concentration, surface curvature, and
      morphology. The polymer layers collapse in aqueous solutions that contain
      sufficient amounts of Ca2+ ions. This collapse, due to the formation of calcium
      bridges, is not only controlled by the calcium ion concentration but also
      strongly influenced by the curvature of the tethering surface. The transition
      from a swollen to a collapsed layer as a function of calcium concentration
      broadens and shifts to lower amounts of calcium ions as a function of the radius
      of cylindrical and spherical nanoparticles. The results show how the interplay
      between calcium binding and surface curvature governs the structural and
      functional properties of the polymer molecules. This would directly impact the
      fate of weak polyelectrolyte-coated nanoparticles in biological environments, in
      which calcium levels are tightly regulated. Understanding such interplay would
      also contribute to the rational design and optimization of smart interfaces with
      applications in, e.g., salt-sensitive and ion-responsive materials and devices.

PMID- 29652056
TI  - Poster list.

PMID- 29652059
TI  - Targeted delivery of tungsten oxide nanoparticles for multifunctional anti-tumor
      therapy via macrophages.
AB  - Tumor-associated macrophages are highly versatile effector cells that have been
      used to kill tumor cells. Herein, the macrophages as cell-based biocarriers are
      used for the targeted delivery of photothermal reagents for promoting the
      efficiency of killing tumor cells by activating the anti-tumor immune response
      and photothermal therapy (PTT). In this design, macrophages cause the
      phagocytosis of tumor cells and activate the anti-tumor immune response by
      secreting plenty of cytokines. Meanwhile, to improve the tumor-killing effect and
      track the collaborative therapy system in vivo, a novel nanoplatform based on
      tungsten oxide (W18O49, WO) nanoparticles and fluorescent dyes loaded in
      polylactic-co-glycolic acid (PLGA) for PTT has been successfully constructed.
      Subsequently, the nanoparticles are swallowed by macrophages acting as cell-based
      biocarriers to target the tumor and promote solid tumor ablation in vivo in
      animal experiments. This system is expected to bring a huge application potential
      in the visually guided dual-modal therapeutic platform for tumor targeting
      therapy in vivo.

PMID- 29652060
TI  - Redox deracemization of 1,3,4,9-tetrahydropyrano[3,4-b]indoles.
AB  - The existing asymmetric synthesis of enantiopure alpha-substituted cyclic ethers
      predominantly relies on the enantioselective C-C bond formation involving a
      prochiral oxocarbenium ion intermediate. In such a strategy, enantioselectivity
      and efficiency are typically susceptible to the electronic and substituent
      effects of either nucleophile or electrophile partners. Here, we describe a
      strategically different redox deracemization of alpha-substituted 1,3,4,9
      tetrahydropyrano[3,4-b]indoles. This method exhibits good compatibility with the
      regional variation of the electronic or substituent effect of substrates, thus
      providing a practical and efficient supplement to the traditional strategy.

PMID- 29652061
TI  - Bevacizumab and near infrared probe conjugated iron oxide nanoparticles for
      vascular endothelial growth factor targeted MR and optical imaging.
AB  - Vascular endothelial growth factor (VEGF) plays a pivotal role in the cascade of
      development and progression of cancers. Targeting this cancer hallmark is a
      logical strategy for imaging based cancer detection and monitoring the anti
      angiogenesis treatment. Using Bevacizumab (Avastin(r)), which is a recombinant
      humanized monoclonal antibody directly against VEGF and an angiogenesis
      inhibitor, as a targeting ligand, a multimodal VEGF targeted molecular imaging
      probe was developed by conjugating near infrared dye (NIR830) labeled bevacizumab
      to magnetic iron oxide nanoparticles (IONP) for optical and magnetic resonance
      (MR) imaging of cancers over-expressing VEGF. The targeting effect of NIR830
      bevacizumab-IONPs on VEGF over-expressing cells was investigated by receptor
      mediated cell uptake experiments and a blocking assay using VEGF over-expressing
      4T1 breast cancer cells. Systemic administration of VEGF-targeted NIR830
      bevacizumab-IONPs into mice bearing 4T1 breast tumors resulted in higher
      accumulation of targeting IONPs in tumors compared to non-targeted IONPs.
      Quantitative analysis of T2-weighted MRI at 48 h post-injection revealed that the
      averaged percentage of signal intensity change in tumors treated with NIR830
      bevacizumab-IONPs was 52.4 +/- 11.0% compared to 26.9 +/- 12.4% in controls
      treated with non-targeted IONPs. The results demonstrated the feasibility and
      efficacy of NIR830-bevacizumab-IONPs as a VEGF targeting dual-modality molecular
      imaging probe that can be potentially used for imaging of cancers with VEGF over
      expression and delivery of bevacizumab for imaging guided anti-cancer treatment.

PMID- 29652062
TI  - A highly concentrated phosphate-based electrolyte for high-safety rechargeable
      lithium batteries.
AB  - We prepare a totally nonflammable phosphate-based electrolyte composed of 5 mol L
      1 (M) Li bis(fluorosulfonyl) imide (LiFSI) in a trimethyl phosphate (TMP)
      solvent. The concentrated 5 M LiFSI/TMP electrolyte shows good compatibility with
      graphite and no Al corrosion. More attractively, such a concentrated electrolyte
      can effectively suppress the growth of Li dendrites in Li metal batteries because
      of a stable LiF-rich SEI layer. Therefore, this highly concentrated electrolyte
      is promising for safe Li batteries.

PMID- 29652066
TI  - Investigation of V2O5 as a low-cost rechargeable aqueous zinc ion battery
      cathode.
AB  - Rechargeable aqueous zinc ion batteries (ZIBs) are highly desirable for large
      scale energy storage due to their advantages of safety and low-cost. Development
      of advanced cathodes for use in aqueous ZIBs is urgently needed. Herein, we
      report a low-cost rechargeable aqueous Zn-V2O5 cell with 3 M ZnSO4 electrolyte
      that demonstrates high zinc storage capability. We also investigated the effect
      of different types/concentrations of the aqueous electrolytes on the performance
      of the Zn-V2O5 cells.

PMID- 29652063
TI  - Genetic encoding of 2-aryl-5-carboxytetrazole-based protein photo-cross-linkers.
AB  - Three gamma-heteroatom-substituted N-methylpyrroletetrazole-lysines (mPyTXKs)
      were synthesized and subsequently incorporated into proteins site-specifically
      via genetic code expansion. The gamma-seleno-substituted derivative, mPyTSeK,
      showed excellent incorporation efficiency in Escherichia coli and allowed site
      selective photo-cross-linking of the GST dimer. Furthermore, the mPyTSeK-cross
      linked GST dimer can be cleaved under mild oxidative conditions. The
      incorporation of mPyTXKs into proteins in mammalian cells was also demonstrated.
      Lastly, the recombinantly expressed mPyTSeK-encoded Grb2 was shown to covalently
      capture its interaction partner, EGFR, in mammalian cell lysate, which was
      subsequently released after treatment with H2O2.

PMID- 29652068
TI  - Poster list.

PMID- 29652069
TI  - Silver(i) dithiocarboxylate complexes - clustering and aggregation.
AB  - The neutral silver(i) dithiocarboxylate complexes silver(i) dithioacetate,
      silver(i) pentafluorodithiobenzoate, silver(i) 2,4,6-trimethyldithiobenzoate,
      silver(i) 2,4,6-tri-iso-propyldithiobenzoate and silver(i) 2,6-dimesityl
      dithiobenzoate were synthesized and characterized by IR spectroscopy, elemental
      analyses and single crystal X-ray diffraction. All complexes form primarily
      dinuclear units with eight-membered rings [Ag2S4C2], which in turn aggregate by
      argentophilic interactions and additional AgS contacts in their crystal
      structures. The molecular structures and shapes of aggregation in the solid state
      are presented and discussed. The layer-like and chain-like aggregates as well as
      the [Ag] clusters formed are compared with the (almost) analogous gold(i)
      complexes.

PMID- 29652071
TI  - A thermostated cell for electrochemistry: minimising natural convection and
      investigating the role of evaporation and radiation.
AB  - An optimised thermostated electrochemical cell is designed and implemented. This
      is informed by experimental and computational studies characterizing the extent
      to which the thermostating of an electrochemical cell via a heated bath can be
      realised, both with the cell closed and open to the environment. The heat
      transfer in the system is simulated and probed experimentally; special emphasis
      is put on heat loss due to radiation and evaporation. Experiments and simulations
      demonstrate that these two mechanisms of heat transfer lead to a steady
      temperature in the cell that differs from that of the thermostat by ~0.1 K.
      Simulations indicate that spatial inhomogeneities in the stationary temperature
      drive natural convective flows with a significant velocity. These new physical
      insights inform the optimization of a new electrochemical cell and its
      application in measurements of the impact frequency of silver nanoparticles as a
      function of temperature.

PMID- 29652074
TI  - Outstanding Reviewers for Soft Matter in 2017.

PMID- 29652073
TI  - The iron regulatory proteins are defective in repressing translation via
      exogenous 5' iron responsive elements despite their relative abundance in
      leukemic cellular models.
AB  - In animal cells the specific translational control of proteins contributing to
      iron homeostasis is mediated by the interaction between the Iron Regulatory
      Proteins (IRP1 and IRP2) and the Iron Responsive Elements (IRE) located in the
      untranslated regions (UTR) of regulated messengers, such as those encoding
      ferritin or the transferrin receptor. The absolute concentrations of the
      components of this regulatory system in hematopoietic cells and the ability of
      the endogenous IRP to regulate exogenous IRE have been measured. The IRP
      concentration is in the low MUM (10-6 M) range, whereas the most abundant IRE
      containing messenger RNA (mRNA), i.e. those of the ferritin subunits, do not
      exceed 100 nM (10-7 M). Most other IRP mRNA targets are around or below 1 nM. The
      distribution of the mRNA belonging to the cellular iron network is similar in
      human leukemic cell lines and in normal cord blood progenitors, with differences
      among the cellular models only associated with their different propensities to
      synthesize hemoglobin. Thus, the IRP regulator is in large excess over its
      presently identified regulated mRNA targets. Yet, despite this excess, endogenous
      IRP poorly represses translation of transfected luciferase cDNA engineered with a
      series of IRE sequences in the 5' UTR. The cellular concentrations of the central
      hubs of the mammalian translational iron network will have to be included in the
      description of the proliferative phenotype of leukemic cells and in assessing any
      therapeutic action targeting iron provision.

PMID- 29652075
TI  - Impact of TGF-beta family-related growth factors on chondrogenic differentiation
      of adipose-derived stem cells isolated from lipoaspirates and infrapatellar fat
      pads of osteoarthritic patients.
AB  - The success of cell-based approaches for the treatment of cartilage defects
      requires an optimal autologous cell source with chondrogenic differentiation
      ability that maintains its differentiated properties and stability following
      implantation. The objective of this study was to compare the chondrogenic
      capacity of mesenchymal stem cells (MSCs) isolated from lipoaspirates (ASCs) and
      the infrapatellar fat pad (IFPSCs) of osteoarthritic patients and treated with
      transforming growth factor (TGF)-beta family-related growth factors. Cells were
      cultured for 6 weeks in a 3D pellet culture system with the chimeric activin
      A/bone morphogenic protein (BMP)-2 ligand (AB235), the chimeric nodal/BMP-2
      ligand (NB260) or BMP-2. To investigate the stability of the new cartilage, ASCs
      treated pellets were transplanted subcutaneously into severe combined
      immunodeficiency (SCID) mice. Histological and immunohistochemical assessment
      confirmed that the growth factors induced cartilage differentiation in both
      isolated cell types. However, reverse transcription-quantitative PCR results
      showed that ASCs presented a higher chondrogenic potential than IFPSCs. In vivo
      results revealed that AB235-treated ASCs pellets were larger in size and could
      form stable cartilage-like tissue as compared to NB260-treated pellets, while BMP
      2-treated pellets underwent calcification. The chondrogenic induction of ASCs by
      AB235 treatment was mediated by SMAD2/3 activation, as proved by
      immunofluorescence analysis. The results of this study indicated that the
      combination of ASCs and AB235 might lead to a cell-based cartilage regeneration
      treatment.

PMID- 29652076
TI  - Systematic reanalysis of genomic data improves quality of variant interpretation.
AB  - As genomic sequencing expands, so does our knowledge of the link between genetic
      variation and disease. Deeper catalogs of variant frequencies improve
      identification of benign variants, while sequencing affected individuals reveals
      disease-associated variation. Accumulation of human genetic data thus makes
      reanalysis a means to maximize the benefits of clinical sequencing. We
      implemented pipelines to systematically reassess sequencing data from 494
      individuals with developmental disability. Reanalysis yielded pathogenic or
      likely pathogenic (P/LP) variants that were not initially reported in 23
      individuals, 6 described here, comprising a 16% increase in P/LP yield. We also
      downgraded 3 LP and 6 variants of uncertain significance (VUS) due to updated
      population frequency data. The likelihood of identifying a new P/LP variant
      increased over time, as ~22% of individuals who did not receive a P/LP variant at
      their original analysis subsequently did after 3 years. We show here that
      reanalysis and data sharing increase the diagnostic yield and accuracy of
      clinical sequencing.

PMID- 29652077
TI  - The implications of cocaine use and associated behaviors on adverse
      cardiovascular outcomes among veterans: Insights from the VA Clinical Assessment,
      Reporting, and Tracking (CART) Program.
AB  - BACKGROUND: Cocaine use has been associated with adverse cardiovascular outcomes
      in patients with coronary artery disease (CAD). It is unclear whether this is due
      to direct effects of cocaine or other factors. HYPOTHESIS: Cocaine use is
      associated with worse outcomes in patients undergoing cardiac catheterization
      METHODS: We used the Veterans Affairs database to identify veterans undergoing
      coronary catheterization between 2007 and 2014. We analyzed association between
      cocaine use and 1-year all-cause mortality, myocardial infarction (MI), and
      cerebrovascular accident (CVA) among veterans with obstructive CAD (N = 122 035).
      To explore factors contributing to these associations, we sequentially adjusted
      for cardiac risk factors, risky behaviors, and clinical conditions directly
      affected by cocaine. RESULTS: 3082 (2.5%) veterans were cocaine users. Cocaine
      users were younger (median 58.2 vs 65.3 years; P < 0.001), more likely to be
      African American (58.9% vs 10.6%; P < 0.001), and had fewer traditional cardiac
      risk factors. After adjustment for cardiac risk factors, cocaine was associated
      with increased risk of mortality (HR: 1.23, 95% CI: 1.08-1.39), MI (HR: 1.40, 95%
      CI: 1.07-1.83), and CVA (HR: 1.88, 95% CI: 1.38-2.57). With continued adjustment,
      increased CVA risk remained significantly associated with cocaine use, whereas MI
      risk was mediated by risky behaviors and mortality was fully explained by
      conditions directly affected by cocaine. CONCLUSIONS: Cocaine use is associated
      with adverse cardiac events in veterans with CAD. Contributors to this
      association are multifaceted and specific to individual cardiovascular outcomes,
      including associated risky behaviors and direct effects of cocaine. Effective
      intervention programs to reduce cardiac events in this population will require
      multiple components addressing these factors.

PMID- 29652078
TI  - Total cardiovascular events analysis of the EXAMINE trial in patients with type 2
      diabetes and recent acute coronary syndrome.
AB  - Alogliptin, a dipeptidyl peptidase-4 inhibitor, is approved for the treatment of
      patients with type 2 diabetes (T2DM). EXAMINE was a randomized controlled
      clinical trial designed to demonstrate the cardiovascular (CV) safety of
      alogliptin. In the trial, 5380 patients with established T2DM who had a recent
      acute coronary syndrome event (between 15 and 90 days) were randomized to
      treatment with either alogliptin or placebo. To better understand and describe
      the CV safety of alogliptin, we analyzed data from the EXAMINE trial to determine
      whether treatment with alogliptin affected recurrent and total CV events. Poisson
      regression analysis compared the total number of occurrences of CV death, MI,
      stroke, unstable angina, and coronary revascularization between all patients
      randomized to alogliptin vs placebo groups. Patients with recurrent CV events
      were older and more likely to have renal disease and history of heart failure.
      There were 1100 first CV events and an additional 666 recurrent events over a
      median of 18 months of follow-up. There were no significant differences with
      regard to total number of events in patients treated with alogliptin (n = 873) or
      placebo (n = 893; P = 0.52). Furthermore, there were no differences in the types
      of events seen in patients treated with alogliptin or placebo. Alogliptin did not
      increase the risk of either first or recurrent CV events when compared with
      placebo in patients with T2DM and recent acute coronary syndrome. These data
      support the CV safety of alogliptin in patients who are at increased risk of
      future CV events.

PMID- 29652079
TI  - Meta-analysis of an artery-first approach versus standard pancreatoduodenectomy
      on perioperative outcomes and survival.
AB  - BACKGROUND: The aim of this systematic review and meta-analysis was to evaluate
      perioperative outcomes and survival in patients undergoing an artery-first
      approach to pancreatoduodenectomy in comparison with those having standard
      pancreatoduodenectomy. METHODS: A systematic search of PubMed, MEDLINE, Embase
      and the Cochrane Database of Systematic Reviews was performed in accordance with
      PRISMA guidelines. Comparative studies including patients who underwent artery
      first pancreatoduodenectomy and standard pancreatoduodenectomy were analysed.
      RESULTS: Seventeen studies were included in the final analysis. There were 16
      retrospective cohort or case-control studies and one RCT. A total of 1472
      patients were included in the meta-analysis, of whom 771 underwent artery-first
      pancreatoduodenectomy and 701 had standard pancreatoduodenectomy. Intraoperative
      blood loss (mean difference -389 ml; P < 0.001) and the proportion of patients
      requiring intraoperative transfusion (10.6 per cent (54 of 508) versus 40.1 per
      cent (186 of 464); P < 0.001) were significantly lower in the artery-first group.
      Although rates of perioperative mortality were comparable between the two groups,
      perioperative morbidity (35.5 per cent (263 of 741) versus 44.3 per cent (277 of
      625); P = 0.002), and the incidence of grade B/C pancreatic fistula (7.4 per cent
      (26 of 353) versus 12.8 per cent (42 of 327); P = 0.031) were significantly lower
      in the artery-first group. The R0 resection rate (75.8 per cent (269 of 355)
      versus 67.0 per cent (280 of 418); P < 0.001) and overall survival (hazard ratio
      0.72, 95 per cent c.i. 0.60 to 0.87; P < 0.001) were significantly higher in the
      artery-first group. CONCLUSION: The artery-first approach to
      pancreatoduodenectomy may be associated with improved perioperative outcomes and
      survival.

PMID- 29652080
TI  - Multicentre observational study of adherence to Sepsis Six guidelines in
      emergency general surgery.

PMID- 29652081
TI  - Eight-year follow-up of a randomized clinical trial comparing ultrasound-guided
      foam sclerotherapy with surgical stripping of the great saphenous vein.
AB  - BACKGROUND: This was an 8-year follow-up of an RCT comparing ultrasound-guided
      foam sclerotherapy (UGFS) with high ligation and surgical stripping (HL/S) of the
      great saphenous vein (GSV). METHODS: Patients were randomized to UGFS or HL/S of
      the GSV. The primary outcome was the recurrence of symptomatic GSV reflux.
      Secondary outcomes were patterns of reflux according to recurrent varices after
      surgery, Clinical Etiologic Anatomic Pathophysiologic (CEAP) classification,
      Venous Clinical Severity Score (VCSS) and EuroQol Five Dimensions (EQ-5DTM)
      quality-of-life scores. RESULTS: Of 430 patients originally randomized (230 UGFS,
      200 HL/S), 227 (52.8 per cent; 123 UGFS, 103 HL/S) were available for analysis
      after 8 years. The proportion of patients free from symptomatic GSV reflux at 8
      years was lower after UGFS than HL/S (55.1 versus 72.1 per cent; P = 0.024). The
      rate of absence of GSV reflux, irrespective of venous symptoms, at 8 years was
      33.1 and 49.7 per cent respectively (P = 0.009). More saphenofemoral junction
      (SFJ) failure (65.8 versus 41.7 per cent; P = 0.001) and recurrent reflux in the
      above-knee GSV (72.5 versus 20.4 per cent; P = 0.001) was evident in the UGFS
      group. The VCSS was worse than preoperative scores in both groups after 8 years;
      CEAP classification and EQ-5D(r) scores were similar in the two groups.
      CONCLUSION: Surgical stripping had a technically better outcome in terms of
      recurrence of GSV and SFJ reflux than UGFS in the long term. Long-term follow-up
      suggests significant clinical progression of venous disease measured by VCSS in
      both groups, but less after surgery. Registration number: NCT02304146
      (http://www.clinicaltrials.gov).

PMID- 29652082
TI  - Association between hospital volume and quality of gastric cancer surgery in the
      CRITICS trial.
AB  - BACKGROUND: Studies investigating the association between hospital volume and
      quality of gastric cancer surgery are lacking. In the present study, the effect
      of hospital volume on quality of gastric cancer surgery was evaluated by
      analysing data from the CRITICS (ChemoRadiotherapy after Induction chemotherapy
      In Cancer of the Stomach) trial. METHODS: Patients who underwent gastrectomy with
      curative intent in the Netherlands were selected from the CRITICS trial database.
      Annual hospital volume of participating centres was derived from the Netherlands
      Cancer Registry. Hospital volume was categorized into very low (1-10
      gastrectomies per year per institution), low (11-20), medium (21-30) and high (31
      or more), and linked to the CRITICS database. Quality of surgery was analysed by
      surgicopathological compliance (removal of at least 15 lymph nodes), surgical
      compliance (removal of indicated lymph node stations) and the Maruyama Index.
      Postoperative morbidity and mortality were also compared between hospital
      categories. RESULTS: Between 2007 and 2015, 788 patients were included in the
      CRITICS study, of whom 494 were analysed. Surgicopathological compliance was
      higher (86.7 versus 50.4 per cent; P < 0.001), surgical compliance was greater
      (52.9 versus 19.8 per cent; P < 0.001) and median Maruyama Index was lower (0
      versus 6; P = 0.006) in high-volume hospitals compared with very low-volume
      hospitals. There was no statistically significant difference in postoperative
      complications or mortality between the hospital volume categories. CONCLUSION:
      Surgery performed in high-volume hospitals was associated with better surgical
      quality than surgery carried out in lower-volume hospitals.

PMID- 29652083
TI  - Progress and future direction in the management of advanced colorectal cancer.

PMID- 29652085
TI  - Advanced colorectal cancer issue.

PMID- 29652086
TI  - Five-year follow-up of a randomized clinical trial comparing open surgery, foam
      sclerotherapy and endovenous laser ablation for great saphenous varicose veins.
AB  - BACKGROUND: New treatment methods have challenged open surgery as a treatment for
      great saphenous vein (GSV) insufficiency, the most common being ultrasound-guided
      foam sclerotherapy (UGFS) and endovenous laser ablation (EVLA). This study
      evaluated the long-term results of surgery, EVLA and UGFS in the treatment of GSV
      reflux. METHODS: Patients with symptomatic GSV reflux were randomized to undergo
      either open surgery, EVLA or UGFS. The main outcome measure was the occlusion
      rate of the GSV at 5 years after operation. RESULTS: The study included 196
      patients treated during 2008-2010; of these, 166 (84.7 per cent) participated in
      the 5-year follow-up. At 5 years, the GSV occlusion rate was 96 (95 per cent c.i.
      91 to 100) per cent in the open surgery group, 89 (82 to 98) per cent after EVLA
      and 51 (38 to 64) per cent after UGFS (P < 0.001). For patients who had received
      no additional treatment during follow-up, the occlusion rates were 96 per cent
      (46 of 48), 89 per cent (51 of 57) and 41 per cent (16 of 39) respectively. UGFS
      without further GSV treatment was successful in only 16 of 59 patients (27 per
      cent) at 5 years. CONCLUSION: UGFS has significantly inferior occlusion rates
      compared with open surgery or EVLA, and results in additional treatments.

PMID- 29652087
TI  - Expanding the clinical spectrum of biallelic ZNF335 variants.
AB  - ZNF335 plays an essential role in neurogenesis and biallelic variants in ZNF335
      have been identified as the cause of severe primary autosomal recessive
      microcephaly in 2 unrelated families. We describe, herein, 2 additional affected
      individuals with biallelic ZNF335 variants, 1 individual with a homozygous c.1399
      T > C, p.(Cys467Arg) variant, and a second individual with compound heterozygous
      c.2171_2173delTCT, p.(Phe724del) and c.3998A > G, p.(Glu1333Gly) variants with
      the latter variant predicted to affect splicing. Whereas the first case presented
      with early death and a severe phenotype characterized by anterior agyria with
      prominent extra-axial spaces, absent basal ganglia, and hypoplasia of the
      brainstem and cerebellum, the second case had a milder clinical presentation with
      hypomyelination and otherwise preserved brain structures on MRI. Our findings
      expand the clinical spectrum of ZNF335-associated microcephaly.

PMID- 29652088
TI  - Non-invasive brain stimulation techniques for chronic pain.
AB  - BACKGROUND: This is an updated version of the original Cochrane Review published
      in 2010, Issue 9, and last updated in 2014, Issue 4. Non-invasive brain
      stimulation techniques aim to induce an electrical stimulation of the brain in an
      attempt to reduce chronic pain by directly altering brain activity. They include
      repetitive transcranial magnetic stimulation (rTMS), cranial electrotherapy
      stimulation (CES), transcranial direct current stimulation (tDCS), transcranial
      random noise stimulation (tRNS) and reduced impedance non-invasive cortical
      electrostimulation (RINCE). OBJECTIVES: To evaluate the efficacy of non-invasive
      cortical stimulation techniques in the treatment of chronic pain. SEARCH METHODS:
      For this update we searched CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, LILACS
      and clinical trials registers from July 2013 to October 2017. SELECTION CRITERIA:
      Randomised and quasi-randomised studies of rTMS, CES, tDCS, RINCE and tRNS if
      they employed a sham stimulation control group, recruited patients over the age
      of 18 years with pain of three months' duration or more, and measured pain as an
      outcome. Outcomes of interest were pain intensity measured using visual analogue
      scales or numerical rating scales, disability, quality of life and adverse
      events. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted
      and verified data. Where possible we entered data into meta-analyses, excluding
      studies judged as high risk of bias. We used the GRADE system to assess the
      quality of evidence for core comparisons, and created three 'Summary of findings'
      tables. MAIN RESULTS: We included an additional 38 trials (involving 1225
      randomised participants) in this update, making a total of 94 trials in the
      review (involving 2983 randomised participants). This update included a total of
      42 rTMS studies, 11 CES, 36 tDCS, two RINCE and two tRNS. One study evaluated
      both rTMS and tDCS. We judged only four studies as low risk of bias across all
      key criteria. Using the GRADE criteria we judged the quality of evidence for each
      outcome, and for all comparisons as low or very low; in large part this was due
      to issues of blinding and of precision.rTMSMeta-analysis of rTMS studies versus
      sham for pain intensity at short-term follow-up (0 to < 1 week postintervention),
      (27 studies, involving 655 participants), demonstrated a small effect with
      heterogeneity (standardised mean difference (SMD) -0.22, 95% confidence interval
      (CI) -0.29 to -0.16, low-quality evidence). This equates to a 7% (95% CI 5% to
      9%) reduction in pain, or a 0.40 (95% CI 0.53 to 0.32) point reduction on a 0 to
      10 pain intensity scale, which does not meet the minimum clinically important
      difference threshold of 15% or greater. Pre-specified subgroup analyses did not
      find a difference between low-frequency stimulation (low-quality evidence) and
      rTMS applied to the prefrontal cortex compared to sham for reducing pain
      intensity at short-term follow-up (very low-quality evidence). High-frequency
      stimulation of the motor cortex in single-dose studies was associated with a
      small short-term reduction in pain intensity at short-term follow-up (low-quality
      evidence, pooled n = 249, SMD -0.38 95% CI -0.49 to -0.27). This equates to a 12%
      (95% CI 9% to 16%) reduction in pain, or a 0.77 (95% CI 0.55 to 0.99) point
      change on a 0 to 10 pain intensity scale, which does not achieve the minimum
      clinically important difference threshold of 15% or greater. The results from
      multiple-dose studies were heterogeneous and there was no evidence of an effect
      in this subgroup (very low-quality evidence). We did not find evidence that rTMS
      improved disability. Meta-analysis of studies of rTMS versus sham for quality of
      life (measured using the Fibromyalgia Impact Questionnaire (FIQ) at short-term
      follow-up demonstrated a positive effect (MD -10.80 95% CI -15.04 to -6.55, low
      quality evidence).CESFor CES (five studies, 270 participants) we found no
      evidence of a difference between active stimulation and sham (SMD -0.24, 95% CI 
      0.48 to 0.01, low-quality evidence) for pain intensity. We found no evidence
      relating to the effectiveness of CES on disability. One study (36 participants)
      of CES versus sham for quality of life (measured using the FIQ) at short-term
      follow-up demonstrated a positive effect (MD -25.05 95% CI -37.82 to -12.28, very
      low-quality evidence).tDCSAnalysis of tDCS studies (27 studies, 747 participants)
      showed heterogeneity and a difference between active and sham stimulation (SMD 
      0.43 95% CI -0.63 to -0.22, very low-quality evidence) for pain intensity. This
      equates to a reduction of 0.82 (95% CI 0.42 to 1.2) points, or a percentage
      change of 17% (95% CI 9% to 25%) of the control group outcome. This point
      estimate meets our threshold for a minimum clinically important difference,
      though the lower confidence interval is substantially below that threshold. We
      found evidence of small study bias in the tDCS analyses. We did not find evidence
      that tDCS improved disability. Meta-analysis of studies of tDCS versus sham for
      quality of life (measured using different scales across studies) at short-term
      follow-up demonstrated a positive effect (SMD 0.66 95% CI 0.21 to 1.11, low
      quality evidence).Adverse eventsAll forms of non-invasive brain stimulation and
      sham stimulation appear to be frequently associated with minor or transient side
      effects and there were two reported incidences of seizure, both related to the
      active rTMS intervention in the included studies. However many studies did not
      adequately report adverse events. AUTHORS' CONCLUSIONS: There is very low-quality
      evidence that single doses of high-frequency rTMS of the motor cortex and tDCS
      may have short-term effects on chronic pain and quality of life but multiple
      sources of bias exist that may have influenced the observed effects. We did not
      find evidence that low-frequency rTMS, rTMS applied to the dorsolateral
      prefrontal cortex and CES are effective for reducing pain intensity in chronic
      pain. The broad conclusions of this review have not changed substantially for
      this update. There remains a need for substantially larger, rigorously designed
      studies, particularly of longer courses of stimulation. Future evidence may
      substantially impact upon the presented results.

PMID- 29652090
TI  - Erratum.

PMID- 29652089
TI  - Crises and Population Health.

PMID- 29652091
TI  - Hunger makes apex predators do risky things.
AB  - In Focus: Blecha, K. A., Boone, R. B., & Alldredge, M. W. (2018). Hunger mediates
      apex predator's risk avoidance response in wildland-urban interface. Journal of
      Animal Ecology, 87, 609-622. https://doi.org/10.1111/1365-2656.12801 Puma (Puma
      concolor), an apex predator, can live at the edge of cities where pockets of low
      density human dwellings form residential patches in the wildland-urban interface.
      Blecha, Boone, and Alldredge () tracked puma via global positioning system (GPS)
      telemetry collars to determine when and where they hunted and made kills. Well
      fed puma (1-2 days between kills) strongly avoided residential patches despite
      these areas having higher mule deer (Odocoileus hemionus) densities and higher
      kill success for puma. However, the strong avoidance of residential patches
      completely disappeared as puma became hungrier (4-10 days since last kill) making
      it more likely that hungry individuals hunted in residential areas and ultimately
      increasing the likelihood of puma-human conflict.

PMID- 29652092
TI  - Erratum.

PMID- 29652093
TI  - And the winner of the inaugural Sidnie Manton Award is....

PMID- 29652094
TI  - From in vivo to in vitro: How the Guatemala STD Experiments Transformed Bodies
      Into Biospecimens.
AB  - : Policy Points: While most scholarship regarding the US Public Health Service's
      STD experiments in Guatemala during the 1940s has focused on the intentional
      exposure experiments, secondary research was also conducted on biospecimens
      collected from these subjects. These biospecimen experiments continued after the
      Guatemala grant ended, and the specimens were used in conjunction with those from
      the Tuskegee syphilis experiments for ongoing research. We argue there should be
      a public accounting of whether there are still biospecimens from the Guatemala
      and Tuskegee experiments held in US government biorepositories today. If such
      specimens exist, they should be retired from US government research archives
      because they were collected unethically as understood at the time. CONTEXT: The
      US Public Health Service's Guatemala STD experiments (1946-1948) included
      intentional exposure to pathogens and testing of postexposure prophylaxis methods
      for syphilis, gonorrhea, and chancroid in over 1,300 soldiers, commercial sex
      workers, prison inmates, and psychiatric patients. Though the experiments had
      officially ended, the biospecimens collected from these subjects continued to be
      used for research at least into the 1950s. METHODS: We analyzed historical
      documents-including clinical and laboratory records, correspondence, final
      reports, and medical records-for information relevant to these biospecimen
      experiments from the US National Archives. In addition, we researched material
      from past governmental investigations into the Guatemala STD experiments,
      including those of the US Presidential Commission for the Study of Bioethical
      Issues and the Guatemalan Comision Presidencial para el Esclarecimiento de los
      Experimentos Practicados con Humanos en Guatemala. FINDINGS: Identified spinal
      fluid, blood specimens, and tissue collected during the Guatemala diagnostic
      methodology and intentional exposure experiments were subsequently distributed to
      laboratories throughout the United States for use in ongoing research until at
      least 1957. Five psychiatric patient subjects involved in these biospecimen
      experiments died soon after experimental exposure to STDs. The same US government
      researchers working with the Guatemala biospecimens after the exposure
      experiments ended were also working with specimens taken from the Tuskegee
      syphilis study. CONCLUSIONS: There should be a complete public accounting of
      whether biospecimens from the Guatemala and Tuskegee experiments are held in US
      government biorepositories today. If they still exist, these specimens should be
      retired from such biorepositories and their future disposition determined by
      stakeholders, including representatives from the communities from which they were
      derived.

PMID- 29652095
TI  - Decreases in neprilysin and vasoconstrictors and increases in vasodilators
      following bariatric surgery.
AB  - The aim of this study was to determine if weight loss following Roux-en-Y gastric
      bypass (RYGB) surgery in morbidly obese patients is associated with a decrease in
      plasma concentrations of neprilysin, mediators of the renin angiotensin system
      (RAS), catecholamines and endothelin-1, and also with an increase in the
      concentrations of vasodilators. Fasting blood samples were obtained from 15
      patients with morbid obesity and diabetes prior to and 6 months after RYGB
      surgery. Circulating levels of neprilysin, vasoconstrictors, vasodilators, and
      the mRNA expression of related genes in circulating mononuclear cells (MNC) were
      measured. Six months after RYGB surgery the concentrations of neprilysin,
      angiotensinogen, angiotensin II, renin and endothelin-1 fell significantly by 27
      +/-16%, 22 +/-10%, 22 +/-8%, 35 +/-13% and 17 +/-6% (P < .05 for all),
      respectively, while ANP concentrations increased significantly by 24 +/-13%.
      There was no significant change in aldosterone, BNP, cAMP or cGMP concentrations,
      or angiotensin converting enzyme (ACE) expression. These changes may contribute
      to the reduction of congestive cardiac failure and blood pressure risks after
      RYGB surgery.

PMID- 29652096
TI  - Rapid reconstitution of CMV-specific T-cells after stem-cell transplantation.
AB  - OBJECTIVE: As reconstitution of virus-specific T-cells is critical to control
      cytomegalovirus (CMV)-viremia following stem-cell transplantation (SCT), we
      characterized the dynamics in CMV-specific T-cell reconstitution after SCT.
      METHODS: Cytomegalovirus-specific T-cells from 51 SCT-recipients were
      prospectively quantified and phenotypically characterised by intracellular
      cytokine-staining after specific stimulation and HLA class-I-specific pentamers
      using flow cytometry. RESULTS: Cytomegalovirus-specific CD4 T-cells reconstituted
      after a median of 2.3 (IQR, 2.0-3.0) weeks following autografting, and 4.0 (IQR,
      3.0-5.6) weeks after allografting, with CMV-specific T-cells originating from
      donors and/or recipients. The time for reconstitution of CMV-specific CD4 and CD8
      T-cells did not differ (P = .58). Factors delaying the time to initial
      reconstitution of CMV-specific CD4 T-cells included a negative recipient
      serostatus (P = .016) and CMV-viremia (P = .026). Percentages of CMV-specific CD4
      T-cells significantly increased over time and reached a plateau after 90 days (P
      = .043). Relative CMV-specific CD4 T-cell levels remained higher in long-term
      transplant recipients compared with those in controls (P < .0001). However, due
      to persisting lymphopenia, absolute numbers of CMV-specific T-cells were similar
      as in controls. CONCLUSION: Cytomegalovirus-specific T-cells rapidly reconstitute
      after SCT and their percentages remain high in the long term. In the face of
      persistent lymphopenia, this results in similar absolute numbers of CMV-specific
      T-cells as in controls to ensure sufficient pathogen control.

PMID- 29652097
TI  - Outside-in control - does plant cell wall integrity regulate cell cycle
      progression?
AB  - During recent years it has become accepted that plant cell walls are not inert
      objects surrounding all plant cells but are instead highly dynamic, plastic
      structures. They are involved in a large number of cell biological processes and
      contribute actively to plant growth, development and interaction with
      environment. Therefore, it is not surprising that cellular processes can control
      plant cell wall integrity (CWI) while, simultaneously, CWI can influence cellular
      processes. In yeast and animal cells such a bidirectional relationship also
      exists between the yeast/animal extracellular matrices and the cell cycle. In
      yeast, the CWI maintenance mechanism and a dedicated plasma membrane integrity
      checkpoint are mediating this relationship. Recent research has yielded insights
      into the mechanism controlling plant cell wall metabolism during cytokinesis.
      However, the knowledge regarding putative regulatory pathways controlling
      adaptive modifications in plant cell cycle activity in response to changes in the
      state of the plant cell wall are not yet identified. In this review, we summarize
      similarities and differences in regulatory mechanisms coordinating extracellular
      matrices and cell cycle activity in animal and yeast cells, discuss the available
      evidence supporting the existence of such a mechanism in plants and suggest that
      the plant CWI maintenance mechanism might also control cell cycle activity in
      plant cells.

PMID- 29652098
TI  - Monitoring progress towards the first UNAIDS target: understanding the impact of
      people living with HIV who re-test during HIV-testing campaigns in rural
      Mozambique.
AB  - INTRODUCTION: Awareness of HIV-infection goes beyond diagnosis, and encompasses
      understanding, acceptance, disclosure and initiation of the HIV-care. We aimed to
      characterize the HIV-positive population that underwent repeat HIV-testing
      without disclosing their serostatus and the impact on estimates of the first
      UNAIDS 90 target. METHODS: This analysis was nested in a prospective cohort
      established in southern Mozambique which conducted three HIV-testing modalities:
      voluntary counselling and testing (VCT), provider-initiated counselling and
      testing (PICT) and home-based testing (HBT). Participants were given the
      opportunity to self-report their status to lay counsellors and HIV-positive
      diagnoses were verified for previous enrolment in care. This study included 1955
      individuals diagnosed with HIV through VCT/PICT and 11,746 participants of a HBT
      campaign. Those who did not report their serostatus prior to testing, and were
      found to have a previous HIV-diagnosis, were defined as non-disclosures. Venue
      stratified descriptive analyses were performed and factors associated with non
      disclosure were estimated through log-binomial regression. RESULTS: In the first
      round of 2500 adults randomized for HBT, 1725 were eligible for testing and 18.7%
      self-reported their HIV-positivity. Of those tested with a positive result, 38.9%
      were found to be non-disclosures. Similar prevalence of non-disclosures was found
      in clinical-testing modalities, 29.4% (95% CI 26.7 to 32.3) for PICT strategy and
      13.0% (95% CI 10.9 to 15.3) for VCT. Prior history of missed visits (adjusted
      prevalence ratio (APR) 4.2, 95% CI 2.6 to 6.8), younger age (APR 2.5, 95% CI 1.4
      to 4.4) and no prior history of treatment ((APR) 1.4, 95% CI 1.0 to 2.1) were
      significantly associated with non-disclosure as compared to patients who self
      reported. When considering non-disclosures as people living with HIV (PLWHIV)
      aware of their HIV-status, the proportion of PLWHIV aware increased from 78.3%
      (95% CI 74.2 to 81.6) to 86.8% (95% CI 83.4 to 89.6). CONCLUSION: More than one
      third of individuals testing HIV-positive did not disclose their previous
      positive HIV-diagnosis to counsellors. This proportion varied according to
      testing modality and age. In the absence of an efficient and non-anonymous
      tracking system for HIV-testers, repeat testing of non-disclosures leads to
      wasted resources and may distort programmatic indicators. Developing
      interventions that ensure appropriate psychosocial support are needed to
      encourage this population to disclose their status and optimize scarce resources.

PMID- 29652099
TI  - A novel dynamic opto-thermo-mechanical stress testing device 1: Design of the
      device.
AB  - This article presents a dynamic opto-thermo-mechanical stress testing device to
      characterize fiber properties. The device has multi-modes and consists of many
      functions. These modes include stretching, bending, rotating, twisting, and
      heating processes. Every process can be controlled by micro-controller unit via
      software programs specially designed for this purpose. The micro-controller unit
      can execute two different processes at the same time. Such as, dynamic stretching
      process under the effect of thermal treatment, dynamic stretching process and
      relaxation, bending process under the effect of thermal treatment, and so forth.
      Software programs with their flow charts are designed for the application of
      these processes. The advantage of this device is that it can be done statically
      and dynamically to characterize all types of fibers (polymer and optical). The
      device is designed to be attached with two-beam polarizing interference
      microscope to investigate the dynamic opto-thermo-mechanical properties of the
      tested fiber under the effect of different applied stresses. Isotactic
      polypropylene, iPP, fiber is used for some applications of this device, as
      examples, in stretching, rotation, and twisting modes. Interferograms and graphs
      are given for illustration.

PMID- 29652101
TI  - Switching from sitagliptin to liraglutide to manage patients with type 2 diabetes
      in the UK: A long-term cost-effectiveness analysis.
AB  - AIMS: The recent LIRA-SWITCH trial showed that switching from sitagliptin 100 mg
      to liraglutide 1.8 mg led to statistically significant and clinically relevant
      improvements in glycated haemoglobin (HbA1C) and body mass index (BMI). Based on
      these findings, the aim of the present study was to assess the long-term cost
      effectiveness of switching from sitagliptin to liraglutide in patients with type
      2 diabetes in the UK. MATERIALS AND METHODS: The IQVIA CORE Diabetes Model
      Version 8.5+ was used to project costs and clinical outcomes over patients'
      lifetimes. Baseline cohort characteristics and treatment effects were derived
      from the LIRA-SWITCH trial. Future costs and clinical benefits were discounted at
      3.5% annually. Costs were accounted in pounds sterling (GBP) and expressed in
      2016 values. One-way and probabilistic sensitivity analyses were performed.
      RESULTS: Model projections showed improved quality-adjusted life expectancy for
      patients with poorly controlled HbA1c upon switching from sitagliptin to
      liraglutide, compared with continuing sitagliptin treatment (9.18 vs 9.02 quality
      adjusted life years [QALYs]). Treatment switching was associated with increased
      overall costs (GBP 24737 vs GBP 22362). Higher pharmacy costs were partially
      offset by reduced diabetes-related complication costs in patients who switched to
      liraglutide. Switching to liraglutide was associated with an incremental cost
      effectiveness ratio of GBP 15423 per QALY gained vs continuing with sitagliptin
      treatment. CONCLUSIONS: Switching from sitagliptin 100 mg to liraglutide 1.8 mg
      in patients with poor glycaemic control was projected to improve clinical
      outcomes and is likely to be considered cost-effective in the UK setting and,
      therefore, a good use of limited NHS resources.

PMID- 29652100
TI  - How should HIV resources be allocated? Lessons learnt from applying Optima HIV in
      23 countries.
AB  - INTRODUCTION: With limited funds available, meeting global health targets
      requires countries to both mobilize and prioritize their health spending. Within
      this context, countries have recognized the importance of allocating funds for
      HIV as efficiently as possible to maximize impact. Over the past six years, the
      governments of 23 countries in Africa, Asia, Eastern Europe and Latin America
      have used the Optima HIV tool to estimate the optimal allocation of HIV
      resources. METHODS: Each study commenced with a request by the national
      government for technical assistance in conducting an HIV allocative efficiency
      study using Optima HIV. Each study team validated the required data, calibrated
      the Optima HIV epidemic model to produce HIV epidemic projections, agreed on cost
      functions for interventions, and used the model to calculate the optimal
      allocation of available funds to best address national strategic plan targets.
      From a review and analysis of these 23 country studies, we extract common themes
      around the optimal allocation of HIV funding in different epidemiological
      contexts. RESULTS AND DISCUSSION: The optimal distribution of HIV resources
      depends on the amount of funding available and the characteristics of each
      country's epidemic, response and targets. Universally, the modelling results
      indicated that scaling up treatment coverage is an efficient use of resources.
      There is scope for efficiency gains by targeting the HIV response towards the
      populations and geographical regions where HIV incidence is highest. Across a
      range of countries, the model results indicate that a more efficient allocation
      of HIV resources could reduce cumulative new HIV infections by an average of 18%
      over the years to 2020 and 25% over the years to 2030, along with an
      approximately 25% reduction in deaths for both timelines. However, in most
      countries this would still not be sufficient to meet the targets of the national
      strategic plan, with modelling results indicating that budget increases of up to
      185% would be required. CONCLUSIONS: Greater epidemiological impact would be
      possible through better targeting of existing resources, but additional resources
      would still be required to meet targets. Allocative efficiency models have proven
      valuable in improving the HIV planning and budgeting process.

PMID- 29652102
TI  - Drought reduces floral resources for pollinators.
AB  - Climate change is predicted to result in increased occurrence and intensity of
      drought in many regions worldwide. By increasing plant physiological stress,
      drought is likely to affect the floral resources (flowers, nectar and pollen)
      that are available to pollinators. However, little is known about impacts of
      drought at the community level, nor whether plant community functional
      composition influences these impacts. To address these knowledge gaps, we
      investigated the impacts of drought on floral resources in calcareous grassland.
      Drought was simulated using rain shelters and the impacts were explored at
      multiple scales and on four different experimental plant communities varying in
      functional trait composition. First, we investigated the effects of drought on
      nectar production of three common wildflower species (Lathyrus pratensis,
      Onobrychis viciifolia and Prunella vulgaris). In the drought treatment, L.
      pratensis and P. vulgaris had a lower proportion of flowers containing nectar and
      O. viciifolia had fewer flowers per raceme. Second, we measured the effects of
      drought on the diversity and abundance of floral resources across plant
      communities. Drought reduced the abundance of floral units for all plant
      communities, irrespective of functional composition, and reduced floral species
      richness for two of the communities. Functional diversity did not confer greater
      resistance to drought in terms of maintaining floral resources, probably because
      the effects of drought were ubiquitous across component plant communities. The
      findings indicate that drought has a substantial impact on the availability of
      floral resources in calcareous grassland, which will have consequences for
      pollinator behaviour and populations.

PMID- 29652103
TI  - Ten-year follow-up study of Japanese patients with obsessive-compulsive disorder.
AB  - AIM: Obsessive-compulsive disorder (OCD) is a well-known chronic illness. This
      study retrospectively investigated 10-year outcomes and associated clinical
      factors in Japanese OCD patients. We focused on the impact of several
      sociocultural factors, including medical expenses and insurance systems specific
      to each country, on the differences or biases in follow-up procedures of OCD.
      METHODS: Seventy-nine patients diagnosed with OCD who received a standardized
      combination of treatments for 10 continuous years were divided into three groups
      according to their improvement rates on the Yale-Brown Obsessive-Compulsive Scale
      after 10 years of treatment. RESULTS: A survival analysis revealed that the rate
      of patients achieving full remission increased every year. Following 10 years of
      treatment, 56% of OCD patients experienced 'full remission' for at least 1 year.
      Consequently, 48% exhibited full remission, and 37% exhibited partial remission
      at the end-point of this study. We identified several factors that were
      predictive of poorer outcomes, including lower Global Assessment of Functioning
      Scale scores and the presence of hoarding symptoms or involvement behaviors. In
      addition, improvement rates after 1 year significantly predicted better 10-year
      outcomes. CONCLUSION: Our findings highlight the transcultural nature of long
      term outcomes of OCD treatment, which appear to be independent of sociocultural
      differences.

PMID- 29652104
TI  - The influence of lead nanoparticles on the morpho-functional changes of rat liver
      during the postexposure period.
AB  - Lead as any heavy metals may be found in soil, water, air, and is used in
      everyday life. Once in the body, it causes toxic effect, making the liver, which
      is one of the main organs of detoxification, suffer. Recently, the study of the
      action of not only ionic forms of lead, but also its nanoparticles, has become
      topical. The study aims at determining changes in the liver of rats and
      biochemical changes in their blood both at late term of exposure to nanoparticles
      of lead compounds and in the post-exposure period. The study was performed on 120
      male rats of Wistar line, which were divided into two series, each series
      containing four groups. The first and the second groups of animals were
      intraperitoneally injected with colloidal solution of nanoparticles of lead
      sulfide of 10 and 30 nm in size, and the third group were intraperitoneally
      injected with a solution of lead nitrate. The fourth group of animals served as
      control. In the first series, the investigated substances were administered 60
      times within 12 weeks. In the second series, after 60-fold administration of the
      investigated substances, the exposure was discontibued and animals were observed
      for 6 weeks-overall duration of 18 weeks. Histological, morphometrical and
      biochemical methods were used. The body weight was reduced in the rats exposed to
      PbSnano1 at week 12 of experiment and in rats exposed to both PbSnano1 and Pb(NO3
      )2 in the second series. Absolute liver weight increased at week 12 of experiment
      in all experimental groups. In the second series this value almost reached that
      of the control level. Relative liver weight in the animals of all experimental
      groups was higher than that in the control at week 12 of experiment. In the
      second series this value remained higher in rats exposed to PbSnano1 . After 12
      weeks of exposure dystrophic changes in the liver were found in all experimental
      groups. At week 6 after the exposure (the second series) destructive changes in
      the liver decreased. Total protein, albumin, glucose, total lipids, cholesterol,
      triglycerides content in blood serum corresponded with morphological data. The
      experiment has demonstrated that the 12 weeks long exposure to lead nanoparticles
      had harmful effect on the liver. Within the postexposure 6-weeks period
      structural changes in the liver and biochemical changes in blood serum decreased.
      Biochemical changes in blood serum corresponded to the morphological data. By
      many parameters PbSnano1 had more pronounced harmful effect. Toxicity of PbSnano2
      and Pb(NO3 )2 were comparable.

PMID- 29652105
TI  - Associations between problematic Internet use and psychiatric symptoms among
      university students in Japan.
AB  - AIM: Research on the adverse effects of Internet use has gained importance
      recently. However, there is currently insufficient data on Japanese young adults'
      Internet use, so we conducted a survey targeting Japanese university students to
      research problematic Internet use (PIU). We also investigated the relationship
      between PIU and multiple psychiatric symptoms. METHODS: A paper-based survey was
      conducted at five universities in Japan. Respondents were asked to fill out self
      report scales regarding their Internet dependency using the Internet Addiction
      Test (IAT). Sleep quality, attention-deficit hyperactivity disorder (ADHD)
      tendency, depression, and anxiety symptom data were also collected based on
      respective self-reports. RESULTS: There were 1336 responses and 1258 were
      included in the analysis. The mean IAT score (+/- SD) was 37.87 +/- 12.59; and
      38.2% of participants were classified as PIU, and 61.8% as non-PIU. The trend
      level for young women showed that they were more likely to be classified as PIU
      than young men (40.6% and 35.2% respectively, P = 0.05). Compared to the non-PIU
      group, the PIU group used the Internet longer (P < 0.001), had significantly
      lower sleep quality (P < 0.001), had stronger ADHD tendencies (P < 0.001), had
      higher Depression scores (P < 0.001), and had higher Trait-Anxiety scores (P <
      0.001). Based on multiple logistic regression analyses, the factors that
      contributed to an increased risk of PIU were: being female (odds ratio [OR] =
      1.52), being older (OR = 1.17), having poor sleep quality (OR = 1.52), having
      ADHD tendencies (OR = 2.70), having depression (OR = 2.24), and having anxiety
      tendencies (OR = 1.43). CONCLUSION: We found a high PIU prevalence among Japanese
      young adults. The factors that predicted PIU were: female sex, older age, poor
      sleep quality, ADHD tendencies, depression, and anxiety.

PMID- 29652106
TI  - Anxious distress in monopolar and bipolar depression: Clinical characteristics
      and relation with mixed depression in Japan.

PMID- 29652107
TI  - Developing a Dental Scrubs Ceremony to define professional identity and teach
      professionalism to dental undergraduates; lessons learned.
AB  - INTRODUCTION: The UK General Dental Council stipulates that professionalism is a
      key aspect of the teaching and training of dental students. However, dental
      educators highlight that teaching dental student's professionalism can be
      challenging and students often rate this teaching activity negatively. This
      article documents a teaching initiative at one UK Dental School that aimed to
      strengthen the professionalism curriculum by introducing a Dental Scrubs Ceremony
      for second-year students. MATERIALS AND METHOD: The Dental Scrubs Ceremony is
      inspired by the White Coat Ceremonies that medical students have in universities
      in North America. It marks the students' first step in their professional and
      clinical development, with the signing of a pledge of conduct and public
      presentation of dental scrubs to each student. We report student feedback
      questionnaire data over a three-year period together with reflections on the
      merits and limitations of this alternative approach to teaching professionalism.
      RESULTS: Student evaluation data show that the perceived usefulness and
      worthwhileness of a Dental Scrubs Ceremony have grown since its inception in
      2015. Most students enjoyed the symbolism of the ceremony, receiving their dental
      scrubs in a formal event. However, there was mixed evaluation for its
      effectiveness to teach professionalism. CONCLUSION: A Dental Scrubs Ceremony is a
      useful addition to the formal curriculum of professionalism in a dental school.
      It provides dental students with an opportunity to be inducted into the dental
      profession as novice dental students starting out on their professional career.

PMID- 29652108
TI  - Skeletal muscle-specific overexpression of heat shock protein 72 improves
      skeletal muscle insulin-stimulated glucose uptake but does not alter whole body
      metabolism.
AB  - AIMS: The induction of heat shock protein 72 (Hsp72) via heating, genetic
      manipulation or pharmacological activation is metabolically protective in the
      setting of obesity-induced insulin resistance across mammalian species. In this
      study, we set out to determine whether the overexpression of Hsp72, specifically
      in skeletal muscle, can protect against high-fat diet (HFD)-induced obesity and
      insulin resistance. MATERIALS AND METHODS: An Adeno-Associated Viral vector
      (AAV), designed to overexpress Hsp72 in skeletal muscle only, was used to study
      the effects of increasing Hsp72 levels on various metabolic parameters. Two
      studies were conducted, the first with direct intramuscular (IM) injection of the
      AAV:Hsp72 into the tibialis anterior hind-limb muscle and the second with a
      systemic injection to enable body-wide skeletal muscle transduction. RESULTS: IM
      injection of the AAV:Hsp72 significantly improved skeletal muscle insulin
      stimulated glucose clearance in treated hind-limb muscles, as compared with
      untreated muscles of the contralateral leg when mice were fed an HFD. Despite
      this finding, systemic administration of AAV:Hsp72 did not improve body
      composition parameters such as body weight, fat mass or percentage body fat, nor
      did it lead to an improvement in fasting glucose levels or glucose tolerance.
      Furthermore, no differences were observed for other metabolic parameters such as
      whole-body oxygen consumption, energy expenditure or physical activity levels.
      CONCLUSIONS: At the levels of Hsp72 over-expression reported herein, skeletal
      muscle-specific Hsp72 overexpression via IM injection has the capacity to
      increase insulin-stimulated glucose clearance in this muscle. However, upon
      systemic injection, which results in lower muscle Hsp72 overexpression, no
      beneficial effects on whole-body metabolism are observed.

PMID- 29652109
TI  - An aspirational diet for dialysis patients: Evidence and theory.
AB  - Dialytic renal replacement therapy is now entering into its sixth decade in the
      United States. Despite major advances in dialysis technology, regimens and
      protocols, and pharmacological treatments, patients' restricted dietary intake
      remains the lynchpin to their well-being and success. Herein, we review current
      guidelines that limit dietary intake of nutrients and minerals in dialysis
      patients and explore potential ways to use them in designing a daily food intake
      that is not only healthy, but also easy to implement and therefore patient
      friendly. The main theme behind this review is attempting to emphasize that
      dietary restriction guidelines can be used in such a way that dialysis patients
      can eat things they really enjoy as long as they follow some relatively simple
      general rules.

PMID- 29652110
TI  - Intranasal glucagon for hypoglycaemia in diabetic patients. An old dream is
      becoming reality?
AB  - In 1983 it was shown that glucagon administered intranasally (IN) was absorbed
      through the nasal mucosa and increased blood glucose in healthy subjects. Shortly
      thereafter, it was shown that IN glucagon counteracts with hypoglycaemia in
      insulin-treated diabetic patients. In spite of this evidence, IN glucagon was not
      developed by any pharmaceutical company before 2010, when renewed interest led to
      intensive evaluation of a possible remedy for hypoglycaemia in insulin-treated
      diabetic adults and children. IN glucagon is now being developed as a needle-free
      device that delivers glucagon powder for treatment of severe hypoglycaemia; the
      ease of using this device stands in stark contrast to the difficulties
      encountered in use of the current intramuscular glucagon emergency kits. Studies
      have demonstrated the efficacy, safety and ease-of-use of this IN glucagon
      preparation, and suggest IN glucagon as a promising alternative to injectable
      glucagon for treating severe hypoglycaemia in children and adults who use
      insulin. This would meet the unmet medical need for an easily administered
      glucagon preparation.

PMID- 29652111
TI  - Actual diagnosis of Helicobacter pylori infection.
AB  - Helicobacter pylori colonizes the stomach of half of humanity. The prevalence of
      this infection is higher among people of low socioeconomic status and from
      developing countries. In the absence of effective antibiotic treatment, the
      infection persists decades or even lifetime. The diagnosis of H. pylori can be
      made by invasive methods when biopsies are obtained: culture, histological
      examination, polymerase chain reaction or rapid urease test. Non-invasive methods
      have been developed, including the urea breath test, a test of high reliability,
      particularly suitable for post-treatment monitoring, but also the fecal antigen
      test, as well as the detection of antibodies in the serum. Culture is important
      for studying sensitivity to antibiotics, in particular clarithromycin and
      fluoroquinolones. The present paper presents the main diagnostic tests available
      today for a modern diagnosis of this bacterial infection discovered over thirty
      years ago.

PMID- 29652112
TI  - Mucopexy-recto anal lifting: a standardized minimally invasive method of managing
      symptomatic hemorrhoids, with an innovative suturing technique and the HemorPex
      System(r).
AB  - BACKGROUND: Conservative surgery of hemorrhoidal disease is less painful than
      traditional hemorrhoidectomy, and mucopexy has less risk of serious postoperative
      complications than stapled hemorrhoidopexy. The aim of this study was to evaluate
      the safety and effectiveness of a standardized, modified hemorrhoidopexy, named
      Mucopexy-Recto Anal Lifting (MuRAL) with the HemorPex System (HPS) in patients
      with symptomatic III and IV degree hemorrhoids. METHODS: Patients were enrolled
      from May 2013 to Dec 2015 and operated on with the MuRAL technique, based on
      arterial ligation and mucopexy at 6 locations, using a standardized
      clockwise/anti-clockwise rotation sequence of the HPS anoscope. Follow-up
      controls were carried out by independent observers, as follows: a digital
      exploration 3 weeks after the intervention, digital exploration plus proctoscopy
      at 3 and 12 months and repeated at a 12 months interval. Patients who did not
      strictly follow the postoperative controls were excluded from the study. Primary
      outcome measurement was the recurrence rate. Secondary measurements were:
      operative time, hospital stay, postoperative pain, postoperative symptoms and
      satisfaction score. RESULTS: We operated on 126 patients (72 males, mean age
      53.9, range 29-83): 87 (69.6%) with III degree and 39 with IV degree hemorrhoids;
      13 patients had a MuRAL as a revisional procedure of a previous operation for
      hemorrhoids. Mean duration of follow-up was 554 days (range 281-1219). Four
      patients were excluded from the study. One-year recurrence rate was 4.1%. The
      mean duration of the intervention was 29.5 minutes (range 23-60) and 92 patients
      (73%) were discharged during the same day of the operation. Pain VAS Score in the
      first, second and third postoperative day was 3.9, 2.5, and 1.9, respectively.
      Twenty-two patients (18%), all submitted to spinal anesthesia, had postoperative
      acute urinary retention. Fecal urgency, observed in 18.8% of patients at the
      first control, disappeared within one year after the operation. Mean time to
      return to normal activity was 8 days (range 5 -10). The patient satisfaction
      scores at one-year follow up were 31.1% excellent, 57.4% good, 7.4% fairly good
      and 4.1% poor. In patients with III degree hemorrhoids operative time was
      significantly shorter, postoperative pain better and transient fecal urgency
      lower than in IV degree patients. In our experience the standardization of MuRAL
      operation with HPS, turned out to be a safe and effective minimally invasive
      approach in managing symptomatic III and IV degree hemorrhoids, avoiding the risk
      of severe complications, with the possibility to perform a redo-MuRAL in the
      event of recurrence. CONCLUSIONS: In our series up to 88% of the patients
      reported a good, or excellent one-year satisfaction score. Further comparative
      randomized studies with longer follow-up period are needed.

PMID- 29652113
TI  - Neutrophil to lymphocyte ratio predicts risk of nodal involvement in T1
      colorectal cancer patients.
AB  - BACKGROUND: Risk of nodal involvement in T1 colorectal cancer is assessed by
      tumor histological features. In several tumors, the ratio between neutrophils and
      lymphocytes (NLR) or platelets and lymphocytes (PLR) have been applied to lymph
      node metastases prediction. The aim of this study was to evaluate the role of
      NLR, derived NLR (dNLR) and PLR in predicting nodal involvement in T1 colorectal
      cancers. METHODS: NLR, dNLR and PLR in surgical resected T1 colorectal cancers
      were retrospectively calculated and analysed in nodal positive and negative
      cases. RESULTS: Data regarding 102 patients were considered. Nodal involvement
      rate was 10.8%. NLR values were higher in node positive patients (P=0.04). A
      trend toward significance (P=0.05) was found for higher dNLR values and positive
      nodal status. For NLR, ROC curve analysis allowed to choose a predictive cut-off
      value of 3.7 (AUC of 0.69; 95% CI: 0.48-0.89). Nodal positivity was reported in
      71.5% of high NLR patients; only two N0 cases (28.5%) were registered in high NLR
      group (P<0.001). The logistic regression analysis aimed to evidence the
      predictive role of high NLR in node positivity resulted in a significant OR of
      37.1 (P<0.0001; 95% CI: 0.48-0.89). NLR allowed to distinguish N0 from N1
      patients in 99.4% of cases. CONCLUSIONS: NLR<3.7 was associated with lower risk
      of lymph-node metastases in T1 colorectal cancer patients. NLR could be used with
      histopathological data to identify patients at lower risk of nodal metastases.

PMID- 29652114
TI  - Associations between vitamin D levels and polycystic ovary syndrome (PCOS)
      phenotypes.
AB  - BACKGROUND: Studies comparing serum 25-hydroxyvitamin D concentrations in women
      with and without PCOS have produced inconsistent results. Additionally, no
      previous studies have evaluated associations between vitamin D and specific PCOS
      phenotypes. METHODS: This case-control study was conducted among women undergoing
      intrauterine insemination. Cases (n=137) were diagnosed with PCOS and then
      further classified into 3 diagnostic phenotypes based on combinations of the
      Rotterdam criteria [ovulatory dysfunction +polycystic ovaries (n=55); ovulatory
      dysfunction +androgen excess (n=15); and ovulatory dysfunction, +polycystic
      ovaries, +androgen excess (n=67)]. Controls (n=103) were ovulatory women without
      PCOS who were undergoing IUI. Serum total 25-hydroxyvitamin D concentrations were
      categorized as deficient (<=20 ng/ml), insufficient (21-29 ng/ml), and sufficient
      (>=30 ng/ml). Prevalence odds ratios (PORs) were calculated using logistic
      regression. RESULTS: A higher proportion (59.9%) of PCOS cases lacked sufficient
      vitamin D levels compared to controls (47.6%; p-value=0.06). The odds of vitamin
      D deficiency in all PCOS cases were twice that of controls (POR=2.03, 95% CI 0.97
      4.26); however, the association was attenuated after adjusting for body mass
      index (BMI) and race/ethnicity (adjPOR=1.43,95% CI 0.62, 3.26). When examining
      PCOS phenotypes exhibiting androgen excess, crude associations were observed for
      deficient vitamin D levels (unadjPOR=2.93, 95% CI: 1.27, 6.77); however, the
      association decreased after adjustment for BMI and race/ethnicity (adjPOR=2.03,
      95% CI: 0.79, 5.19). CONCLUSIONS: Vitamin D deficiency occurred more frequently
      in PCOS cases with androgen excess, but associations were attenuated after
      adjusting for BMI and race/ethnicity. Combining etiologically distinct PCOS
      subgroups may obscure associations with lower vitamin D levels and other
      potential risk factors.

PMID- 29652115
TI  - Analysis on influencing factors of abnormal renal function in elderly patients
      with type 2 diabetes mellitus.
AB  - BACKGROUND: To investigate the related influencing factors of abnormal renal
      function in elderly in patients with type 2 diabetes mellitus (T2DM) and their
      clinical significance. METHODS: The clinical data of elderly T2DM patients
      hospitalized in Beijing Luhe Hospital from January 2013 to June2016 were
      retrospectively analyzed. According to their glomerular filtration rate (GFR)
      levels, these patients were divided into GFR >=90 mL/min/1.73m2 group (Group A),
      GFR =60-90 mL/min/1.73m2 group (Group B), and GFR <60 mL/min/1.73m2 group (Group
      C, i.e., abnormal renal function group). Clinical and laboratory indicators were
      compared among each group. RESULTS: A total of 614 elderly T2DM patients were
      collected and divided into Group A (n=186), Group B (n=280) and Group C (n=148,
      24.10%). Among them, patients clinically diagnosed with diabetic nephropathy (DN)
      accounted for 13.68%, and those complicated with high blood pressure (HBP)
      accounted for 61.40%. In Group C, DN accounted for only 29.73%. In elderly T2DM
      patients, HBP course, systolic blood pressure (SBP), diastolic blood pressure
      (DBP), 2h postprandial blood glucose (2hPBG), serum total cholesterol (TC) and
      blood uric acid (BUA) were independent influencing factors associated with
      abnormal renal function, among which HBP had a more significant impact on
      abnormal renal function. With the increase of blood pressure (BP) level, the
      extension in the course of DM, the increase in urinary albumin/creatinine
      (Alb/Cr) and the decrease in GFR, the incidence rate of abnormal renal function
      was increased. CONCLUSIONS: HBP course, SBP, DBP, 2hPBG, TC and BUA are
      independent risk factors for abnormal renal function in elderly patients with
      T2DM. Well-controlled BP and blood glucose are protective factors, and a
      comprehensive treatment targeting to the above influencing factors has important
      clinical significance in preventing and delaying the occurrence and development
      of abnormal renal function.

PMID- 29652116
TI  - 'Left out in the Cold: Village Women and Agricultural Labour in England and Wales
      during the First World War'.
AB  - The Women's Land Army (WLA), formed in 1917, has featured prominently in recent
      academic and popular account of First World War Britain. This interest reflects
      the attention the WLA drew from politicians, government reporters and
      contemporary commentators during and immediately after the war itself. Yet, the
      WLA, which at its peak had 16,000 women working on the land, was just one strand
      of wartime female agricultural labour, an auxiliary to the thousands of village
      women who worked throughout the war. Whilst the WLA received numerous plaudits
      for their participation, village women were 'left out in the cold', as one
      correspondent to The Times put it, in recognition of their wartime service. This
      article will place the rural woman worker back to centre stage. It will revisit
      the often-contradictory wartime estimates of the number of women working in
      agriculture in England and Wales before moving on to examine how regional farming
      structures and seasonal demands for labour shaped the use of women workers. It
      will show that even at the very local level, here utilizing records from the
      Bedfordshire Women's War Agricultural Committee, demand and supply issues
      produced a fractured pattern. It will show that concentrating exclusively on the
      WLA leads to a distorted picture of women's work on the land during the First
      World War.

PMID- 29652117
TI  - Ocular surface disease incidence in patients with open-angle glaucoma.
AB  - Introduction: Ocular surface disease (OSD) is a multifactorial disease of the
      tears and ocular surface thatresults in symptoms of discomfort, visual
      disturbances, tear film instability with potential damage to theocular surface,
      accompanied by increased tear film osmolarity and inflammation of the ocular
      surface. It isa consequence of disrupted homeostasis of lacrimal functional unit.
      The main pathogenetic mechanismstems from tear hyperosmolarity and tear film
      instability. The etiological classification is hyposecretory(Sy-Sjogren and non
      Sjogren) and evaporative (extrinsic and intrinsic) form. Delphi panel
      classificationgrades disease stages. Antiglaucoma topical therapy causes
      exacerbation or occurrence of symptomsof dry eye due to main ingredients or
      preservatives (benzalkonium chloride - BAK), which are dose- andtime-dependent.
      BAK reduces the stability of the lipid layer of tears, the number of goblet
      cells, inducesapoptosis and inflammatory infiltration. Objective: The aim of this
      study was the analysis of the OSD incidence in open-angle glaucoma patientscaused
      by topical medicamentous therapy. Methods: Retrospective analysis of examined
      patients with open-angle glaucoma was used. Results: Increased incidence of
      moderate and advanced OSD Index degrees in the group of primaryopen-angle
      glaucoma (POAG) and pseudoexfoliative glaucoma. According to the Delphi Panel
      Scale themost common grade is IIb (POAG and pseudoexfoliative glaucoma).
      Evaporative form of OSD prevailedin all treatment groups. High percentage of dry
      eye in patients with higher concentrations of preservativesapplied was noticed.
      Conclusion: OSD should be timely diagnosed and treated. Dry eye has an impact on
      surgical outcomeand postoperative visual acuity, and in order to improve patient
      compliance and quality of life, symptomsof dry eye should be addressed and
      medications with lower concentrations of preservatives should beapplied.

PMID- 29652118
TI  - Graphitic Carbon Nitride (g-C3N4) Nanosheets/Graphene Composites: In Situ
      Synthesis and Enhanced Photocatalytic Performance.
AB  - A facile In Situ growth method was presented here for the preparation of
      graphitic carbon nitride (g-C3N4)/graphene composites, in which the direct growth
      and deposition of g-C3N4 nanosheets from organic N and C sources on the graphene
      surfaces was achieved to form the 3D contacted structure. The resulting 3D
      architecture possessed multilevel porous structure and efficient g-C3N4/graphene
      interfaces, which facilitated the fast electron transfer at the interfaces.
      Photoluminescence spectra showed that the recombination of photogenerated
      electrons and holes in the g-C3N4/graphene composites was greatly inhibited by
      the introduction of graphene, indicating the more efficient separation of
      electrons and hole in the g-C3N4/graphene composites than in pure g-C3N4. The
      catalytic activity of g-C3N4/graphene composite photocatalyst was enhanced by
      over two fold compared to pure g-C3N4 for removal of Rhodamine B under simulated
      sun light irradiation. This work indicates that the metal-free g-C3N4/graphene
      composite photocatalyst is a promising nanomaterial for further applications in
      water treatment.

PMID- 29652119
TI  - Solvent-Mediated Preparation of Zinc Ferrite-Reduced Graphene Oxide
      Nanocomposites and Its Application in Removal of Methylene Blue.
AB  - Zinc ferrite-reduced graphene oxide composites, which could effectively remove
      the methylene blue from aqueous solution, were prepared via a facile solvothermal
      process. These as-prepared samples were characterized by X-ray diffraction,
      transmission electron microscopy, Fourier transform infrared spectroscopy,
      vibration sample magnetometer and UV-vis diffuse reflectance spectroscopy.
      Experimental results showed that solvents played an important role in the
      electron structure of the final samples. Moreover, they influenced the
      photocatalytic performance as well. Among all the samples prepared in different
      solvents, those composites prepared in N-N-dimethylformamide showed the greatest
      performance. They could effectively remove more than 90% of the methylene blue
      from the solution in about 180 min. The efficient removal of target dye turned
      out to be the result of the combination of physical adsorption and photocatalytic
      degradation under visible light irritation. These catalysts showed remarkable
      stability, which could be effectively reused for three times. In addition, all
      these samples showed a certain magnetic response, which was beneficial to
      recycle.

PMID- 29652120
TI  - Guanidino-Graphene Catalysed Synthesis of Flavones via Aldol-Michael-Oxidation.
AB  - Guanidino-graphene has been synthesized by the reaction of bromoamine with
      reduced graphene oxide and characterized by FT-IR, Raman, TGA, powder XRD, TEM,
      SEM, and zeta potential. It is a cheap, heterogeneous and environmentally benign
      solid base catalyst used for cascade Aldol-Michael-oxidation in the synthesis of
      chalcone, flavonoids.

PMID- 29652121
TI  - Electrospun Nanofibers of Poly(lactic acid)/Graphene Nanocomposites .
AB  - Multi-layer graphene (MLG) sheets were obtained by exfoliation of natural
      graphite flakes in chloroform. Dispersions with concentration up to 19 mg/mL were
      prepared. Statistical measurements of MLG sheet sizes by transmission electron
      microscopy showed average width and length of ~340 nm and 860 nm, respectively.
      MLG/chloroform dispersions were used to prepare poly(lactic acid) (PLA)/MLG
      composite fibrillar membranes by electrospinning. A homogeneous distribution of
      MLG into the fibers was observed by optical and scanning electron microscopies.
      The presence of MLG leads to the decrease in the diameter distribution of the
      fibers, which presented average diameter values below 500 nm. Isothermal kinetic
      crystallization of PLA showed to be influenced by the electrospinning process and
      the content of MLG sheets, which acts as nucleating agents.

PMID- 29652122
TI  - PU-Graphene Oxide Composite; Effect of Various Chain Extender on Properties.
AB  - High integration of electronic chip not only improved the electronic device's
      efficiency, but also left the need to stop emitting heat. Thermal interface
      material (TIM) has been proposed to solve this problem. Traditionally, a large
      amount of high thermal conductive materials (such as Cu, Al or AlN) was added for
      better thermal conductivity, which caused undesirable weight-increasing and
      property-sacrificing. Graphene has great thermal conductivity and mechanical
      properties. Furthermore, owing to its low density, it is possible to make a lot
      of TIM even with a small amount. Being composited with PU, it can be an enhanced
      thermal conductive adhesive. Otherwise, amine compound is considered to be
      applicable as both a chain extender of PU and a reducing agent of Graphene oxide
      (GO). In this work, we synthesized PU-GO composite by chemical reaction of NCO
      and GO. We examined the effects of various amine compounds on chemical and
      physical properties of GO and PU-GO composite. Adhesion and thermal properties
      were also studied.

PMID- 29652123
TI  - Nickel Supported on Mesoporous Alumina for Dry Reforming of Methane: Combustion
      Method.
AB  - Ni catalysts supported on ordered mesoporous alumina (OMA) were prepared by EISA
      method and calcined under air and Ar atmospheres. Both catalysts showed stable
      performance for the dry reforming of methane for 24 h, however the catalytic
      activity of Ar calcined catalyst was relatively lower than that in the air
      calcined one. It was found that the carbon (C beta ) layer around nickel
      particles was observed for the Ar calcined catalyst after dry reforming of
      methane. The encapsulating carbon species in the Ar calcined catalyst lowering
      the mass transfer rate of feeds led to lower performance, but no whisker carbon
      was observed. In the case of the air calcined catalyst, whisker carbon (C(v))
      which is inactive during dry reforming was accumulated on the catalyst, and it
      resulted in catalyst breakdown and pressure drop during the reaction.

PMID- 29652124
TI  - Fabrication of Bi-Sb-Te Thermoelectric by Cold-Pressed Sintering for Motorcycle
      Exhaust.
AB  - This study was conducted on the Bi-Sb-Te thermoelectric material which is cold
      pressed Sintering under 750 Mpa to make square thermoelectric pairs with size 8.2
      mm * 8.2 mm and thicknesses 0.8 mm and 1.5 mm. The zone melting method was used
      to acquire P-type thermoelectric material Bi0.4Sb1.6Te3 and N-type thermoelectric
      material Bi2Te2.5Se0.5. At temperature 383 K, the measured Seebeck coefficient of
      Bi0.4Sb1.6Te3 is 222 MUV/K, and its thermoelectric figure of merit ZT is 1.35. At
      temperature 400 K, the measured Seebeck coefficient of Bi2Te2.5Se0.5 is 210
      MUV/K, and its thermoelectric figure of merit ZT is 1.13. Using Solder paste
      Sn42Bi58 and copper electrode plate are in series connection with 16 pieces of
      P/N thermoelectric material to form thermoelectric modules. The thermoelectric
      module is actually pasted on the motorcycle waste heat source to be evaluated the
      performance, making the cold-end temperature dissipation heat can enhance the
      temperature difference between it so as to increase the output power. Increasing
      the leg thickness of thermoelectric module and making the about 35  degrees C
      temperature-difference of those can obviously enhance the performance of in terms
      of its voltage, its thermoelectric figure of merit ZT and output power of the
      thermoelectric modules.

PMID- 29652125
TI  - The Synthesis and Photoluminescent Properties of CaMoO4:Eu3+ Nanocrystals by a
      Soft Chemical Route.
AB  - In this paper, the CaMoO4:Eu3+ phosphors were prepared by a simple hydrothermal
      method assisted by the citric acid as the surfactant, and characterized by X-ray
      diffraction (XRD), field emission scanning electron microscopy (FE-SEM), and
      fluorescent spectrophotometry. The results of XRD show that the as-prepared
      samples are single phase. The process of the Ostwald ripening is controlled by
      the content of the citric acid in the hydrothermal reaction. The pH value of the
      precursor affects the shift of the charge transition band (CTB) in the excitation
      spectra. The reaction condition can strongly affect the luminescent intensity of
      the samples.

PMID- 29652126
TI  - Initial Cell Adhesion onto a Phospholipid Polymer Brush Surface Modified with a
      Terminal Cell Adhesion Peptide.
AB  - Dynamic changes in the properties of adsorbed protein layers at material surfaces
      make it difficult to analyze a cell adhesion behavior. Adhesion is affected by
      the ligand molecules in the adsorbed protein layers on the material's surface.
      This study aimed to quantitatively analyze the initial cell adhesion onto a
      polymeric surface modified with immobilized cell adhesion molecules with a well
      defined structure. Peptides containing an arginine-glycine-aspartic acid (RGD)
      sequence were introduced at almost all the termini of the grafted poly(2
      methacryloyloxyethyl phosphorylcholine) [poly(MPC)] chains using a click reaction
      at a highly protein-resistant poly(MPC) brush layer. Thus, the surface could bind
      to the cell membrane proteins only through the immobilized RGD. Furthermore, the
      degree of polymerization of the grafted poly(MPC) chains could control the
      hydrated poly(MPC) brush layer softness, as determined by measuring the
      dissipation energy loss using a quartz crystal microbalance. At the initial stage
      of cell adhesion, the density of cells adhering to the RGD-immobilized poly(MPC)
      brush layers did not depend on the poly(MPC) brush layer softness. However,
      spreading of the adherent cells was inhibited on the RGD-immobilized poly(MPC)
      brush layers with a higher softness. Hence, the results suggested that the layer
      softness did not affect the binding number between the RGD and cell membrane
      protein during initial cell adhesion; however, the intracellular signaling
      triggered by the RGD-receptor interaction was inhibited. The poly(MPC) brush
      surface carrying immobilized cell adhesion molecules has the potential to analyze
      precisely the effect of the properties of cell adhesion molecules on initial cell
      adhesion.

PMID- 29652128
TI  - Self-Healing Organic Fluorophore of Cyanine-Conjugated Amphiphilic Polypeptide
      for Near-Infrared Photostable Bioimaging.
AB  - Photobleaching and biotoxicity are the main bottlenecks for organic fluorescent
      dyes applied in real-time dynamic monitoring of living cells. Here, an unnatural
      amino acid, 4-nitro-3-phenyl-l-alanine (NPA), was used as a scaffold to
      covalently link a near-infrared fluorophore Cy5.5 and an amphiphilic polypeptide,
      poly[oligo(ethylene glycol) methyl ether methacrylate]- block-poly[2-amino-N4-(2
      diisopropylamino-ethyl)-l-aspartic acid] (P(OEGMA)21-P(Asp)16-iPr), was then
      conjugated for increasing the photostability and improving the biocompatibility
      simultaneously. The protective agent of NPA can service as an effective triplet
      state quenching by intramolecular electron transfer between Cy5.5 and NPA. The
      less sensitivity of the electron-transfer process for molecular oxygen makes it
      an ideal photostabilized strategy for fluorophores applied in live-cell imaging.
      Bonding to copolymer is a common way for hydrophobic dyes to expand their
      application in biomedical imaging and increase their functionality, depending on
      the delivery system. The results indicate that Cy5.5-NPA-linked polypeptide
      copolymer exhibited an enhanced photostability and an excellent biocompatibility,
      which means this scaffolding strategy has a potential application in fluorescence
      guided surgery, lived-cell imaging, and super-resolution microscopy.

PMID- 29652127
TI  - Optical Probes for Neurobiological Sensing and Imaging.
AB  - Fluorescent nanosensors and molecular probes are next-generation tools for
      imaging chemical signaling inside and between cells. Electrophysiology has long
      been considered the gold standard in elucidating neural dynamics with high
      temporal resolution and precision, particularly on the single-cell level.
      However, electrode-based techniques face challenges in illuminating the specific
      chemicals involved in neural cell activation with adequate spatial information.
      Measuring chemical dynamics is of fundamental importance to better understand
      synergistic interactions between neurons as well as interactions between neurons
      and non-neuronal cells. Over the past decade, significant technological advances
      in optical probes and imaging methods have enabled entirely new possibilities for
      studying neural cells and circuits at the chemical level. These optical imaging
      modalities have shown promise for combining chemical, temporal, and spatial
      information. This potential makes them ideal candidates to unravel the complex
      neural interactions at multiple scales in the brain, which could be complemented
      by traditional electrophysiological methods to obtain a full spatiotemporal
      picture of neurochemical dynamics. Despite the potential, only a handful of probe
      candidates have been utilized to provide detailed chemical information in the
      brain. To date, most live imaging and chemical mapping studies rely on
      fluorescent molecular indicators to report intracellular calcium (Ca2+) dynamics,
      which correlates with neuronal activity. Methodological advances for monitoring a
      full array of chemicals in the brain with improved spatial, temporal, and
      chemical resolution will thus enable mapping of neurochemical circuits with finer
      precision. On the basis of numerous studies in this exciting field, we review the
      current efforts to develop and apply a palette of optical probes and nanosensors
      for chemical sensing in the brain. There is a strong impetus to further develop
      technologies capable of probing entire neurobiological units with high
      spatiotemporal resolution. Thus, we introduce selected applications for ion and
      neurotransmitter detection to investigate both neurons and non-neuronal brain
      cells. We focus on families of optical probes because of their ability to sense a
      wide array of molecules and convey spatial information with minimal damage to
      tissue. We start with a discussion of currently available molecular probes,
      highlight recent advances in genetically modified fluorescent probes for ions and
      small molecules, and end with the latest research in nanosensors for biological
      imaging. Customizable, nanoscale optical sensors that accurately and dynamically
      monitor the local environment with high spatiotemporal resolution could lead to
      not only new insights into the function of all cell types but also a broader
      understanding of how diverse neural signaling systems act in conjunction with
      neighboring cells in a spatially relevant manner.

PMID- 29652129
TI  - Decarbonylative Cross-Couplings: Nickel Catalyzed Functional Group
      Interconversion Strategies for the Construction of Complex Organic Molecules.
AB  - The utilization of carboxylic acid esters as electrophiles in metal-catalyzed
      cross-coupling reactions is increasingly popular, as environmentally friendly and
      readily available ester derivatives can be powerful alternatives to the commonly
      used organohalides. However, key challenges associated with the use of these
      chemicals remain to be addressed, including the stability of ester substrates and
      the high energy barrier associated with their oxidative addition to low-valent
      metal species. Due to recent developments in nickel catalysis that make it easier
      to perform oxidative additions, chemists have become interested in applying less
      reactive electrophiles as coupling counterparts in nickel-catalyzed
      transformations. Hence, our group and others have independently investigated
      various ester group substitutions and functionalizations enabled by nickel
      catalysis. Such methods are of great interest as they enable the exchange of
      ester groups, which can be used as directing groups in metal-catalyzed C-H
      functionalizations prior to their replacement. Here, we summarize our recent
      efforts toward the development of nickel-catalyzed decarbonylative cross-coupling
      reactions of carboxylic esters. Achievements accomplished by other groups in this
      area are also included. To this day, a number of new transformations have been
      successfully developed, including decarbonylative arylations, alkylations,
      cyanations, silylations, borylations, aminations, thioetherifications,
      stannylations, and hydrogenolysis reactions. These transformations proceed via a
      nickel-catalyzed decarbonylative pathway and have shown a high degree of
      reactivity and chemoselectivity, as well as several other unique advantages in
      terms of substrate availability, due to the use of esters as coupling partners.
      Although the mechanisms of these reactions have not yet been fully understood,
      chemists have already provided some important insights. For example, Yamamoto
      explored the stoichiometric nickel-mediated decarbonylation process of esters and
      proposed a reaction mechanism involving a C(acyl)-O bond cleavage and a CO
      extrusion. Key nickel intermediates were isolated and characterized by Shi and co
      workers, supporting the assumption of a nickel/ N-heterocyclic carbene-promoted
      C(acyl)-O bond activation and functionalization. Our combined experimental and
      computational study of a ligand-controlled chemoselective nickel-catalyzed cross
      coupling of aromatic esters with alkylboron reagents provided further insight
      into the reaction mechanism. We demonstrated that nickel complexes with bidentate
      ligands favor the C(aryl)-C bond cleavage in the oxidative addition step,
      resulting in decarbonylative alkylations, while nickel complexes with monodentate
      phosphorus ligands promote the activation of the C(acyl)-O bond, leading to the
      production of ketone products. Although more detailed mechanistic investigations
      need to be undertaken, the successful development of decarbonylative cross
      coupling reactions can serve as a solid foundation for future studies. We believe
      that this type of decarbonylative cross-coupling reactions will be of significant
      value, in particularly in combination with the retrosynthetic analysis and
      synthesis of natural products and biologically active molecules. Thus, the
      presented ester substitution methods will pave the way for successful
      applications in the construction of complex frameworks by late-stage modification
      and functionalization of carboxylic acid derivatives.

PMID- 29652130
TI  - In Vivo Targeted, Responsive, and Synergistic Cancer Nanotheranostics by Magnetic
      Resonance Imaging-Guided Synergistic High-Intensity Focused Ultrasound Ablation
      and Chemotherapy.
AB  - As one of the most representative noninvasive therapeutic modalities, high
      intensity focused ultrasound (HIFU) has shown great promise for cancer therapy,
      but its low therapeutic efficacy and biosafety significantly hinder further
      extensive clinical translation and application. In this work, we report on the
      construction of a multifunctional theranostic nanoplatform to synergistically
      enhance the HIFU-therapeutic efficacy based on nanomedicine. A targeted and
      temperature-responsive theranostic nanoplatform (PFH/DOX@PLGA/Fe3O4-FA) has been
      designed and fabricated for efficient ultrasound/magnetic resonance dual-modality
      imaging-guided HIFU/chemo synergistic therapy. Especially, the folate was
      conjugated onto the surface of the nanoplatform for achieving active targeting to
      hepatoma cells by receptor-ligand interaction, which facilitates accumulation of
      the nanoplatforms into the tumor site. The integrated superparamagnetic iron
      oxide nanoparticles could generate the contrast enhancement in T2-weighted
      magnetic resonance imaging. By virtue of the thermal effect as generated by HIFU,
      liquid-gas phase transition of perfluorohexane (PFH) in nanocomposites was
      induced to generate PFH microbubbles, which achieved the contrast-enhanced
      ultrasound imaging and significantly improved the HIFU ablation efficacy. The
      loaded anticancer drugs could be released from the nanocomposites in a
      controllable manner (both pH and HIFU responsiveness). These multifunctional
      nanocomposites have been demonstrated to efficiently suppress the tumor growth
      based on the enhanced and synergistic chemotherapy and HIFU ablation, providing
      an efficient theranostic nanoplatform for cancer treatment.

PMID- 29652131
TI  - Thioflavin T Interaction with Acetylcholinesterase: New Evidence of 1:1 Binding
      Stoichiometry Obtained with Samples Prepared by Equilibrium Microdialysis.
AB  - The aim of the present work was investigation of the fluorescent dye thioflavin T
      (ThT) binding to acetylcholinesterase (AChE). ThT is an effective test for
      protease activity, as well as a probe for amyloid fibril formation. Despite the
      extended and active investigation of ThT-AChE binding, there is still no common
      view on the stoichiometry of this interaction. In particular, there is a
      hypothesis explaining the spectral properties of bound to AChE dye and high
      quantum yield of its fluorescence by formation of dimers or excimers of ThT. In
      order to confirm or deny this hypothesis, we proposed a new experimental approach
      for examination of ThT-AChE interaction based on spectroscopic investigation of
      samples prepared by equilibrium microdialysis. This approach allowed us to prove
      1/1 ThT/AChE binding stoichiometry. The increase of ThT fluorescence quantum
      yield and lifetime accompanying its binding to AChE can be explained by the
      molecular rotor nature of this dye. Together with the coincidence of the
      positions of free and AChE-bound ThT fluorescence spectra, the obtained results
      prove the groundlessness of the hypotheses about ThT aggregation while binding to
      AChE. The model of ThT localization in the active site of AChE was proposed by
      using molecular docking simulations. These results also allowed us to suggest the
      key role of aromatic residues in ThT-AChE interaction, as observed for some
      amyloid fibrils.

PMID- 29652132
TI  - Trimetallic Hybrid Nanoflower-Decorated MoS2 Nanosheet Sensor for Direct in Situ
      Monitoring of H2O2 Secreted from Live Cancer Cells.
AB  - In situ monitoring of hydrogen peroxide (H2O2) secreted from live cells plays a
      critical role in elucidating many cellular signaling pathways, and it is a
      significant challenge to selectively detect these low levels of endogenous H2O2.
      To address this challenge, we report the establishment of a trimetallic hybrid
      nanoflower-decorated MoS2 nanosheet-modified sensor for in situ monitoring of
      H2O2 secreted from live MCF-7 cancer cells. The Au-Pd-Pt nanoflower-dispersed
      MoS2 nanosheets are synthesized by a simple wet-chemistry method, and the
      resulting nanosheet composites exhibit significantly enhanced catalytic activity
      toward electrochemical reduction of H2O2, due to the synergistic effect of the
      highly dispersed trimetallic hybrid nanoflowers and the MoS2 nanosheets, thereby
      resulting in ultrasensitive detection of H2O2 with a subnanomolar level detection
      limit in vitro. Also the immobilization of the laminin glycoproteins on the
      surface of the nanocomposites increases its biocompatibility for cell adhesion
      and growth, which enables in situ electrochemical monitoring of H2O2 directly
      secreted from live cells for potential application of such sensor in cellular
      biology, clinical diagnosis, and pathophysiology.

PMID- 29652133
TI  - Ultrasensitive Single Fluorescence-Labeled Probe-Mediated Single Universal Primer
      Multiplex-Droplet Digital Polymerase Chain Reaction for High-Throughput
      Genetically Modified Organism Screening.
AB  - As genetically modified (GM) technology develops and genetically modified
      organisms (GMOs) become more available, GMOs face increasing regulations and
      pressure to adhere to strict labeling guidelines. A singleplex detection method
      cannot perform the high-throughput analysis necessary for optimal GMO detection.
      Combining the advantages of multiplex detection and droplet digital polymerase
      chain reaction (ddPCR), a single universal primer-multiplex-ddPCR (SUP-M-ddPCR)
      strategy was proposed for accurate broad-spectrum screening and quantification.
      The SUP increases efficiency of the primers in PCR and plays an important role in
      establishing a high-throughput, multiplex detection method. Emerging ddPCR
      technology has been used for accurate quantification of nucleic acid molecules
      without a standard curve. Using maize as a reference point, four heterologous
      sequences ( 35S, NOS, NPTII, and PAT) were selected to evaluate the feasibility
      and applicability of this strategy. Surprisingly, these four genes cover more
      than 93% of the transgenic maize lines and serve as preliminary screening
      sequences. All screening probes were labeled with FAM fluorescence, which allows
      the signals from the samples with GMO content and those without to be easily
      differentiated. This fiveplex screening method is a new development in GMO
      screening. Utilizing an optimal amplification assay, the specificity, limit of
      detection (LOD), and limit of quantitation (LOQ) were validated. The LOD and LOQ
      of this GMO screening method were 0.1% and 0.01%, respectively, with a relative
      standard deviation (RSD) < 25%. This method could serve as an important tool for
      the detection of GM maize from different processed, commercially available
      products. Further, this screening method could be applied to other fields that
      require reliable and sensitive detection of DNA targets.

PMID- 29652134
TI  - Heterobimetallic Lantern Complexes and Their Novel Structural and Magnetic
      Properties.
AB  - As the scale of microelectronic circuit devices approaches the atomic limit, the
      study of molecular-based wires and magnets has become more prevalent. Compounds
      with quasi-1D geometries have been investigated for their electronic conductivity
      and magnetic properties with potential use as nanoscale circuit components and
      information storage devices. To increase the number of compositionally tailored
      molecular systems available to study, we have taken a building-block, bottom-up
      approach to the development of improved electronic structure and magnetic
      properties of quasi-1D arrays. Over the past decade, a large family of asymmetric
      complexes that can assemble into extended arrays has resulted. Lantern (or paddle
      wheel) complexes with conventional {O, O} donor carboxylates are legion, but by
      the use of monothiocarboxylate ligands and hard-soft Lewis acid-base principles,
      dozens of new lantern complexes of the form [PtM(SOCR)4(L)] (M = Mg, Ca, Cr, Mn,
      Fe, Co, Ni, Zn; R = Ph (tba = thiobenzoate), CH3 (SAc = thioacetate); L = neutral
      or anionic ligand) have been prepared. Depending on M and L, new intermolecular
      arrangements have resulted, and the magnetic properties have proven particularly
      interesting. In the solid state, the [PtM(SOCR)4(L)] building blocks are
      sometimes isolated, sometimes form dimers, and can be induced to form infinite
      chains. The versatility of the lantern motif was demonstrated with a range of
      axial ligands to form both terminal and bridged complexes with various 3d metals
      and two different substituted thiocarboxylate backbone ligands. Within the dozens
      of crystallographically characterized compounds that make up this family of
      lanterns, several different structural motifs of solid-state dimerization were
      observed and divided into four distinct categories on the basis of their Pt...Pt
      and Pt...S distances and relative monomer orientations. Among all of these
      compounds, three novel magnetic phenomena were observed. Initially, long-range
      antiferromagnetic coupling between two metals more than 8 A apart was observed in
      solid-state dimers formed via metallophilic Pt...Pt interactions and could
      induced by choice of the terminal L group. An infinite chain was prepared in
      [PtCr(tba)4(NCS)]infinity that displays ferromagnetic coupling between Cr centers
      with J/ kB = 1.7(4) K. Homobimetallic quasi-1D chains of the form
      [Ni2(SOCR)4(L)]infinity (R = Ph, CH3; L = DABCO, pyz) were also prepared with S =
      1 {Ni2} building blocks in which the Ni centers have two different spin states
      with weak antiferromagnetic coupling along the chain, such that -0.18 > J/ kB > 
      0.24 K. In the [Ni2(tba)4(quin)] derivative, a solid-state dimer forms with a
      bridging square conformation by interlantern Ni2S2 interactions and displays
      unusual S = 1 configurations on both Ni centers and weak antiferromagnetic
      coupling between them.

PMID- 29652135
TI  - Low-Cost and Simple Fabrication of Nanoplasmonic Paper for Coupled Chromatography
      Separation and Surface Enhanced Raman Detection.
AB  - Surface-enhanced Raman scattering (SERS) is a powerful analytical tool which
      enables the detection and identification of analytes adsorbed on nanostructured
      noble metals. However, SERS analysis of complex mixtures can be challenging due
      to spectral overlap and interference. In this report, we demonstrate a method to
      simplify the identification of mixed-analyte samples by coupling SERS detection
      with chromatographic separation on a nanoplasmonic paper substrate. This
      "nanopaper" substrate is a silver coated glass microfiber filter paper which
      possesses large SERS enhancement and can serve as a stationary phase in paper
      chromatography. Nanopaper is easily synthesized using the silver mirror reaction,
      making it a highly accessible technology. Nanopaper was successfully used as a
      combined paper chromatography-SERS (PC-SERS) substrate in the separation and
      identification of mixed organic dyes. It was further employed to separate and
      identify lycopene and beta-carotene in commercial food products, demonstrating
      the versatility and utility of nanopaper in the identification of complex
      mixtures.

PMID- 29652136
TI  - Bridging the Gap between tRNA Modifications and the Respiratory Chain.

PMID- 29652138
TI  - Development of a Selective Labeling Probe for Bruton's Tyrosine Kinase
      Quantification in Live Cells.
AB  - As a key regulator of the B-cell receptor signaling pathway, Bruton's tyrosine
      kinase (Btk) has emerged as an important therapeutic target for various
      malignancies and autoimmune disorders. However, data on the expression profiles
      of Btk are lacking. Here, we report the discovery of a new, selective Btk probe
      and of a sandwich-type ELISA quantification method to detect endogenous Btk in
      live cells. We achieved selective labeling of Btk in vivo and quantified Btk
      levels in seven types of human lymphoma cell lines. This quantification method
      provides a powerful tool to study Btk in live cells that may also be useful in
      clinical settings.

PMID- 29652139
TI  - Estimated Emissions from the Prime-Movers of Unconventional Natural Gas Well
      Development Using Recently Collected In-Use Data in the United States.
AB  - Natural gas from shale plays dominates new production and growth. However,
      unconventional well development is an energy intensive process. The prime movers,
      which include over-the-road service trucks, horizontal drilling rigs, and
      hydraulic fracturing pumps, are predominately powered by diesel engines that
      impact air quality. Instead of relying on certification data or outdated emission
      factors, this model uses new in-use emissions and activity data combined with
      historical literature to develop a national emissions inventory. For the diesel
      only case, hydraulic fracturing engines produced the most NO x emissions, while
      drilling engines produced the most CO emissions, and truck engines produced the
      most THC emissions. By implementing dual-fuel and dedicated natural gas engines,
      total fuel energy consumed, CO2, CO, THC, and CH4 emissions would increase, while
      NO x emissions, diesel fuel consumption, and fuel costs would decrease. Dedicated
      natural gas engines offered significant reductions in NO x emissions. Additional
      scenarios examined extreme cases of full fleet conversions. While deep market
      penetrations could reduce fuel costs, both technologies could significantly
      increase CH4 emissions. While this model is based on a small sample size of
      engine configurations, data were collected during real in-use activity and is
      representative of real world activity.

PMID- 29652140
TI  - Intra- versus Intermolecular Carbon-to-Carbon Proton Transfers in the Reactions
      of Arynes with Nitrogen Nucleophiles: A DFT Study.
AB  - Carbon-to-carbon proton transfer (PT) is an elementary reaction in organic
      chemistry. Herein we report a systematic DFT study on the carbon-to-carbon proton
      transfers in the reactions of arynes with nitrogen nucleophiles, including
      tertiary amines, aziridines, imines, and N-heteroarenes. DFT calculations
      indicated that the Gibbs energies of activation for the 1,4- and 1,5-proton
      transfers involved are lower than 20 kcal/mol in most cases. We also found that
      the Bell-Evans-Polanyi principle applies to the 1,4-proton transfers, indicating
      that the more exergonic an intramolecular proton transfer is (the more stable a
      carbanion is generated), the faster it will be. Previous experimental studies
      have shown that, in the presence of a carbon nucleophile (NuH; e.g., CHCl3 and
      MeCN) as the third component (also as the solvent), intermolecular proton
      abstractions may compete with the intramolecular proton transfers and lead to
      different products. Our theoretical rationalization of these competitions is that
      the introduction of an electron-withdrawing group at the acidic site can
      accelerate the intramolecular proton transfer dramatically (owing to the
      generation of a more stable carbanion), making it compete with the intermolecular
      processes. In addition, we have also discussed the competition between intra- and
      intermolecular proton transfers when NuH is used as the reactant rather than the
      solvent.

PMID- 29652141
TI  - Insights into 2- and 4(5)-Nitroimidazole Decomposition into Relevant Ions and
      Molecules Induced by VUV Ionization.
AB  - Nitromidazoles are relevant compounds of multidisciplinary interest, and
      knowledge of their physical-chemical parameters as well as their decomposition
      under photon irradiation is needed. Here we report an experimental and
      theoretical study of the mechanisms of VUV photofragmentation of 2- and 4(5)
      nitromidazoles, compounds used as radiosensitizers in conjunction with
      radiotherapy as well as high-energy density materials. Photoelectron-photoion
      coincidence experiments, measurements of the appearance energies of the most
      important ionic fragments, density functional theory, and single-point coupled
      cluster calculations have been used to provide an overall insight into the
      energetics and structure of the different ionic/neutral products of the
      fragmentation processes. The results show that these compounds can be an
      efficient source of relevant CO, HCN, NO, and NO2 molecules and produce ions of
      particular astrophysical interest, like the isomers of azirinyl cation ( m/ z
      40), predicted to exist in the interstellar medium, and protonated hydrogen
      cyanide ( m/ z 28).

PMID- 29652142
TI  - Enantioselective Bioaccumulation and Toxicity of the Neonicotinoid Insecticide
      Dinotefuran in Earthworms ( Eisenia fetida).
AB  - The enantioselective bioaccumulation and toxicity of dinotefuran in earthworms
      were studied in this study. The results showed that S-dinotefuran accumulated
      faster than Rac-dinotefuran and R-dinotefuran in earthworms. The acute toxicity
      of S-dinotefuran was 1.49 and 2.67 times that of the Rac-dinotefuran and R
      dinotefuran in artificial soil during 14 days of exposure. At 1.0 mg/kg, the
      three tested chemicals inhibited the growth and reproduction as well as induced
      oxidative stress effects in earthworms; however, the toxic effects induced by S
      dinotefuran were the most serious. The transcriptome sequencing results showed
      that S-dinotefuran had stronger interactions to biomacromolecules and influences
      on the endoplasmic reticulum (ER) than R-dinotefuran, which may be the main
      reason for enantioselectivities between the two enantiomers. The present results
      indicated that the risk of S-dinotefuran was higher than that of Rac-dinotefuran
      and R-dinotefuran in the soil environment to earthworms. Risk assessment of
      dinotefuran should be evaluated at the enantiomer level.

PMID- 29652143
TI  - Reviewing Hit Discovery Literature for Difficult Targets: Glutathione Transferase
      Omega-1 as an Example.
AB  - Early stage drug discovery reporting on relatively new or difficult targets is
      often associated with insufficient hit triage. Literature reviews of such targets
      seldom delve into the detail required to critically analyze the associated
      screening hits reported. Here we take the enzyme glutathione transferase omega-1
      (GSTO1-1) as an example of a relatively difficult target and review the
      associated literature involving small-molecule inhibitors. As part of this
      process we deliberately pay closer-than-usual attention to assay interference and
      hit quality aspects. We believe this Perspective will be a useful guide for
      future development of GSTO1-1 inhibitors, as well serving as a template for
      future review formats of new or difficult targets.

PMID- 29652144
TI  - Assessment of the Minor-Component Transformations in Fat during the Green Spanish
      Style Table Olive Processing.
AB  - There is an increasing interest of consumers for natural and healthy products.
      This work assesses the transformations that green Spanish-style processing of
      Manzanilla and Hojiblanca table olives produces on the minor components of their
      fat. Discriminant analysis showed that most of the variability was not due to
      processing (24.4%) but to differences between cultivars (59.2%). Therefore, the
      final products have a similar quality to the original olive fat; that is, the
      quality of the fat was scarcely affected. The only systematic trends observed
      were the decrease in hexacosanol, tetracosanol, and octacosanol (fatty alcohols)
      and C46 (wax), after lye treatment, and the high levels of alkyl esters in the
      packaged product. Thus, minor-component levels in green table olives are, in
      general, within the limits established for extra virgin olive oil since the alkyl
      esters should be considered habitual products of fermentation and not as an
      alteration as in olive oil.

PMID- 29652145
TI  - Michael Additions Catalyzed by a beta-Diketiminate-Supported Aluminum Complex.
AB  - A beta-diketiminate-supported aluminum bistriflate complex
      (DipLAl(OTf)2.Na[BArCl4]; DipL = CH(CMe)2(N-C6H3-iPr2)2; Tf = O2SCF3; ArCl = 3,5
      Cl2-C6H3) has been identified as an efficient Lewis acid catalyst for Michael
      additions involving numerous electron-rich (hetero)aromatic substrates and
      several alpha,beta-unsaturated carbonyl compounds. In a vast majority of the
      attempted Michael reactions our catalytic system was significantly superior over
      the currently used methods for the same transformations in terms of reaction
      times and temperatures, catalyst loadings, isolated product yields, and/or
      selectivity.

PMID- 29652146
TI  - Dissolution Dynamic Nuclear Polarization at Room Temperature Using Photoexcited
      Triplet Electrons.
AB  - Dissolution dynamic nuclear polarization (DNP) has recently gained attention as a
      method to enhance the sensitivity of liquid NMR spectroscopy and MRI. We
      demonstrate dissolution of the sample hyperpolarized by DNP using photoexcited
      triplet electrons in 0.38 T at room temperature. The achieved polarization of
      0.8% is 6100 times as high as that at thermal equilibrium under the condition.
      The result is an important step for DNP using photoexcited triplet electrons to
      become widely used in chemical and biomedical research.

PMID- 29652147
TI  - Generation and Reactions of an Octacyclic Hindered Pyramidalized Alkene.
AB  - Octacyclo[10.6.1.01,10.03,7.04,9.08,19.011,16.013,17]nonadeca-5,8,14-triene (27),
      a hindered pyramidalized alkene, has been generated from a diiodide precursor.
      Contrary to the usual behavior of known pyramidalized alkenes, no Diels-Alder
      adducts were obtained from the present alkene when it was generated by different
      standard procedures in the presence of different dienes. However, products
      derived from the reduction, t-BuLi addition, condensation with the solvent, or
      dimerization were isolated from these reactions, depending on the conditions used
      to generate it. No [2 + 2] cross product among this pyramidalized alkene and
      tricyclo[3.3.1.03,7]non-3(7)-ene was formed when a mixture of the corresponding
      precursor diiodides was reacted with sodium amalgam. The analysis of selected
      geometrical and orbital parameters determined from quantum mechanical
      calculations indicates that the degree of pyramidalization of this alkene and its
      higher steric hindrance compared with other polycyclic pyramidalized alkenes may
      explain its peculiar reactivity.

PMID- 29652148
TI  - Organic-Inorganic Hybrid Ruddlesden-Popper Perovskites: An Emerging Paradigm for
      High-Performance Light-Emitting Diodes.
AB  - Recently, lead halide perovskite materials have attracted extensive interest, in
      particular, in the research field of solar cells. These materials are fascinating
      "soft" materials with semiconducting properties comparable to the best inorganic
      semiconductors like silicon and gallium arsenide. As one of the most promising
      perovskite family members, organic-inorganic hybrid Ruddlesden-Popper perovskites
      (HRPPs) offer rich chemical and structural flexibility for exploring excellent
      properties for optoelectronic devices, such as solar cells and light-emitting
      diodes (LEDs). In this Perspective, we present an overview of HRPPs on their
      structural characteristics, synthesis of pure HRPP compounds and thin films,
      control of their preferential orientations, and investigations of heterogeneous
      HRPP thin films. Based on these recent advances, future directions and prospects
      have been proposed. HRPPs are promising to open up a new paradigm for high
      performance LEDs.

PMID- 29652150
TI  - Tunable Synthesis of Functionalized Cyclohexa-1,3-dienes and 2
      Aminobenzophenones/Benzoate from the Cascade Reactions of Allenic
      Ketones/Allenoate with Amines and Enones.
AB  - A TEMPO-dependent tunable synthesis of functionalized cyclohexa-1,3-dienes and 2
      aminobenzophenones/benzoate from the one-pot cascade reactions of allenic
      ketones/allenoate with amines and enones is presented. Mechanistically, the
      construction of the entitled six-membered carbocycles involves the in situ
      generation of an enaminone intermediate via the conjugate addition of allenic
      ketone with amine followed by its catalyst- and base-free [3+3] annulation with
      enone along with the simultaneous introduction of the valuable amino and carbonyl
      groups.

PMID- 29652149
TI  - Zero-Dimensional Cesium Lead Halides: History, Properties, and Challenges.
AB  - Over the past decade, lead halide perovskites (LHPs) have emerged as new
      promising materials in the fields of photovoltaics and light emission due to
      their facile syntheses and exciting optical properties. The enthusiasm generated
      by LHPs has inspired research in perovskite-related materials, including the so
      called "zero-dimensional cesium lead halides", which will be the focus of this
      Perspective. The structure of these materials is formed of disconnected lead
      halide octahedra that are stabilized by cesium ions. Their optical properties are
      dominated by optical transitions that are localized within the individual
      octahedra, hence the title "'zero-dimensional perovskites". Controversial results
      on their physical properties have recently been reported, and the true nature of
      their photoluminescence is still unclear. In this Perspective, we will take a
      close look at these materials, both as nanocrystals and as bulk crystals/thin
      films, discuss the contrasting opinions on their properties, propose potential
      applications, and provide an outlook on future experiments.

PMID- 29652151
TI  - EPR Spectroscopy of Radical Ions of a 2,3-Diamino-1,4-naphthoquinone Derivative.
AB  - We report the electron paramagnetic resonance spectra of the radical cation and
      radical anion of 1,2,2,3-tetramethyl-2,3-dihydro-1 H-naphtho[2,3- d]imidazole-4,9
      dione (1) and its doubly 13C labeled analogue 2, of interest for singlet fission.
      The hyperfine coupling constants are in excellent agreement with density
      functional theory calculations and establish the structures beyond doubt. Unlike
      the radical cation 1*+, the radical anion 1*- and its parent 1 have pyramidalized
      nitrogen atoms and inequivalent methyl groups 15 and 16, in agreement with the
      calculations. The distinction is particularly clear with the labeled analogue 2*
      .

PMID- 29652152
TI  - Surface Separation and in Situ Structural Regulation of Photosensitive Oligomer
      in a Flexible Template.
AB  - Surface-selective adsorption and separation are very important for the
      application of surface functional materials. In this study, a photosensitive
      diazo-macrocycle has been synthesized by the solvent method with a very low
      yield, which can adsorb onto the substrate surface modified with a template
      molecule. By using this flexible template on the graphite surface, a simple
      separation strategy for the macrocyclic molecule with specific shape and size
      from reaction mixtures was developed. Additionally, one of the two azo units in
      this trapped photosensitive macrocycle could convert from trans to cis
      conformation under UV irradiation due to the steric effect. Our results provide a
      new way to construct functional nanodevices using a surface flexible template as
      the separation and regulation medium.

PMID- 29652153
TI  - Petasis-Type gem-Difluoroallylation Reactions Assisted by the Neighboring
      Hydroxyl Group in Amines.
AB  - A three-component Petasis-type gem-difluoroallylation reaction of using pinacol
      gem-difluoroallylboronates, aldehydes or isatin, and beta-amino alcohols enabled
      by the neighboring hydroxyl group in amine is reported, affording various racemic
      and chiral gem-difluorohomoallylamine derivatives with good to excellent results.
      Based on the control experiment and stereochemistry of the product, a proposed
      reaction pathway is illustrated to clarify the origin of regio- and
      stereoselectivity under protic solvent conditions.

PMID- 29652154
TI  - Angular-Shaped Naphthalene Bis(1,5-diamide-2,6-diylidene)malononitrile for High
      Performance, Air-Stable N-Type Organic Field-Effect Transistors.
AB  - The synthesis, characterization, and application of two angular-shaped
      naphthalene bis(1,5-diamide-2,6-diylidene)malononitriles (NBAMs) as high
      performance air-stable n-type organic field effect transistor (OFET) materials
      are reported. NBAM derivatives exhibit deep lowest-unoccupied molecular orbital
      (LUMO) levels, suitable for air-stable n-type OFETs. The OFET device based on
      NBAM-EH fabricated by vapor deposition exhibits a maximum electron mobility of
      0.63 cm2 V-1 s-1 in air with an on/off current ratio ( Ion/ Ioff) of 105.

PMID- 29652155
TI  - Development of Planar Chiral Iodoarenes Based on [2.2]Paracyclophane and Their
      Application in Catalytic Enantioselective Fluorination of beta-Ketoesters.
AB  - The design and synthesis of novel planar chiral iodoarenes based on
      [2.2]paracyclophane is reported. A process of highly enantioselective oxidative
      fluorination of a beta-ketoester with 3HF-Et3N as a nucleophilic fluoride source
      mediated by these new hypervalent iodine catalysts has been developed. This
      represents the first highly enantioselective reaction catalyzed by planar chiral
      hypervalent iodine.

PMID- 29652156
TI  - Zipping-Depinning: Dissolution of Droplets on Micropatterned Concentric Rings.
AB  - The control of the surface wettability is of great interest for technological
      applications as well as for the fundamental understanding of surface phenomena.
      In this article, we describe the dissolution behavior of droplets wetting a
      micropatterned surface consisting of smooth concentric circular grooves. In the
      experiments, a droplet of alcohol (1-pentanol) is placed onto water-immersed
      micropatterns. When the drops dissolve, the dynamics of the receding contact line
      occurs in two different modes. In addition to the stick-jump mode with jumps from
      one ring to the next inner one, our study reveals a second dissolution mode,
      which we refer to as zipping-depinning. The velocity of the zipping-depinning
      fronts is governed by the dissolution rate. At the early stage of the droplet
      dissolution, our experimental results are in good agreement with the theoretical
      predictions by Debuisson et al. [ Appl. Phys. Lett. 2011 , 99 , 184101 ]. With an
      extended model, we can accurately describe the dissolution dynamics in both stick
      jump and zipping-depinning modes.

PMID- 29652157
TI  - Asymmetric Reaction of p-Quinone Diimide: Organocatalyzed Michael Addition of
      alpha-Cyanoacetates.
AB  - Hitherto unknown catalytic enantioselective transformation of p-quinone diimides
      is achieved using chiral bifunctional organic molecules. Bifunctional thiourea
      compounds catalyze the Michael addition of cyanoacetates with excellent yields
      and enantioselectivities. The initially formed Michael adducts undergo
      cyclization to yield functionally rich, fused cyclic imidines bearing a
      quaternary benzylic chiral center. Density functional theory calculations of the
      competing transition states (TSs) were carried out to explain the observed
      stereochemical outcome.

PMID- 29652158
TI  - Unveiling Charge-Density Wave, Superconductivity, and Their Competitive Nature in
      Two-Dimensional NbSe2.
AB  - Recently, charge-density wave (CDW) and superconductivity are observed to coexist
      in atomically thin metallic NbSe2. Lacking of knowledge on the structural details
      of CDW, however, prevents us to explore its interplay with superconductivity.
      Using first-principles calculations, we identify the ground state 3 * 3 CDW
      atomic structure of monolayer NbSe2, which is characterized by the formation of
      triangular Nb clusters and shows a scanning tunnelling microscopy (STM) image and
      Raman CDW modes in good agreement with experiments. We further demonstrate that
      from bulk to monolayer NbSe2, as the layer thickness decreases, the CDW order is
      gradually enhanced with rising energy gain and strengthened Fermi surface
      gapping, while superconductivity is weakened due to the increasingly reduced
      Fermi level density of states in the CDW state. These results well explain the
      observed opposite thickness dependencies of CDW and superconducting transition
      temperatures and uncover the nature of competitive interaction between the two
      collective orders in two-dimensional NbSe2.

PMID- 29652159
TI  - Correction for Rapid Decoherence Suppresses Charge Recombination in Multilayer 2D
      Halide Perovskites: Time-Domain Ab Initio Analysis.

PMID- 29652161
TI  - Synthesis of Side-Chain Locked Analogs of 1alpha,25-Dihydroxyvitamin D3 Bearing a
      C17 Methyl Group.
AB  - A convergent synthesis of side-chain locked vitamin D analogs 3 and 4, which bind
      strongly in silico to the vitamin D receptor (VDR), is described. The synthetic
      approach features an SN2'- syn displacement of carbamates by cuprates to set the
      challenging quaternary stereogenic center at C17 and a Pd-catalyzed construction
      of the triene system in the presence of a diyne moiety.

PMID- 29652160
TI  - Photoredox-catalyzed Direct Reductive Amination of Aldehydes without an External
      Hydrogen/Hydride Source.
AB  - The direct reductive amination of aromatic aldehydes has been realized using a
      photocatalyst under visible light irradiation. The single electron oxidation of
      an in situ formed aminal species generates the putative alpha-amino radical that
      eventually delivers the reductive amination product. This method is operationally
      simple, highly selective, and functional group tolerant, which allows the direct
      synthesis of benzylic amines by a unique mechanistic pathway.

PMID- 29652162
TI  - pHP-Tethered N-Acyl Carbamate: A Photocage for Nicotinamide.
AB  - The synthesis of a new photocaged nicotinamide having an N-acyl carbamate linker
      and a p-hydroxyphenacyl (pHP) chromophore is described. The photophysical and
      photochemical studies showed an absorption maximum at lambda = 330 nm and a
      quantum yield for release of 11% that are dependent upon both pH and solvent.
      While the acyl carbamate releases nicotinamide efficiently, a simpler amide
      linker was inert to photocleavage. This photocaged nicotinamide has significant
      advantages with respect to quantum yield, absorbance wavelength, rate of release,
      and solubility that make it the first practical example of a photocaged amide.

PMID- 29652163
TI  - Gold-catalyzed Bicyclization of Diaryl Alkynes: Synthesis of Polycyclic Fused
      Indole and Spirooxindole Derivatives.
AB  - An unprecedented gold-catalyzed bicyclization reaction of diaryl alkynes has been
      developed for the synthesis of indoles in good to high yields. Mechanistically,
      this alkyne bifunctionalization transformation was terminated by a stepwise
      formal X-H insertion reaction to furnish the corresponding polycyclic-frameworks
      with structural diversity, and the key intermediate 3 H-indole was isolated and
      characterized for the first time. In addition, further transformation of these
      generated tetracyclic-indoles with PCC as the oxidant provided straightforward
      access to the spirooxindoles in high yields.

PMID- 29652164
TI  - alpha-Ketocarbenium Ions Derived from Orthoquinone-Containing Polycyclic Aromatic
      Compounds.
AB  - alpha-Ketocarbenium ions derived from synthesized orthoquinone-containing
      polycyclic aromatic compounds were generated in the presence of Bronsted acids
      such as sulfuric acid, trifluoromethanesulfonic acid, and fluorosulfonic acid.
      The prepared alpha-ketocarbenium ions were stabilized by conjugation of the
      aromatic moiety. In addition, unique absorption properties of the alpha
      ketocarbenium ions were observed and identified on the basis of the calculated
      absorption spectra. It was suggested that the zigzag-shaped architecture
      stabilizes the newly discovered alpha-ketocarbenium ions derived from
      orthoquinone-containing polycyclic aromatic compounds.

PMID- 29652165
TI  - Exploring the Predictors of Emergency Department Triage Acuity Assignment in
      Patients With Sepsis.
AB  - Background and purpose Evidence suggests that septic patients, who require prompt
      medical attention, may be undertriaged, resulting in delayed treatment. The
      purpose of this study was to examine patient and contextual variables that
      contribute to high- versus low-acuity triage classification of patients with
      sepsis. Methods Data were abstracted from the medical records of 154 adult
      patients with sepsis admitted to hospital through a Canadian Emergency
      Department. Logistic regression was used to explore the predictors of triage
      classification. Results Language barriers or chronic cognitive impairment (odds
      ratio 5.7; 95% confidence interval 2.15, 15.01), acute confusion (odds ratio 3.4;
      confidence interval 1.3, 8.2), unwell appearance (odds ratio 3.4; 95% confidence
      interval 1.7, 7.0), and hypotension (odds ratio 0.98; confidence interval 0.96,
      1.0) were predictive of higher acuity classification. Temperature, heart rate,
      respiratory rate, and contextual factors were not related to triage
      classification. Conclusions Several patient-related factors were related to
      triage classification. However, the finding that temperature and heart and
      respiratory rates were not related to triage classification was troubling. Our
      findings point to a need for enhanced education for triage nurses regarding the
      physiological indices of sepsis. The sensitivity of the Canadian Triage
      Assessment Scale, used in Canadian Emergency Rooms, also needs to be examined.

PMID- 29652166
TI  - Ambulance use, distance and outcomes in patients with suspected cardiovascular
      disease: a registry-based geographic information system study.
AB  - BACKGROUND: Despite guideline recommendations, the majority of patients with
      symptoms suggestive of acute coronary syndrome do not use emergency medical
      services to reach the emergency department (ED). The aim of this study was to
      investigate the factors associated with EMS utilisation and subsequent patient
      outcomes. METHODS: Using administrative data, all patients who presented to an ED
      in the metropolitan areas of Edmonton and Calgary in the years of 2007-2013 with
      main ED diagnosis of acute coronary syndrome, stable angina or chest pain were
      included. The travel distance was estimated using the geographic information
      system method to approximate the distance between the ED and patient home. The
      clinical endpoints were the 7-day and 30-day all-cause events (death, re
      hospitalisation and repeat ED visit). RESULTS: Of 50,881 patients, 30.5%
      presented by emergency medical services. Patients with older age, female sex, ED
      diagnosis of acute coronary syndrome, more comorbidities and lower household
      income were more likely to use emergency medical services to reach the hospital.
      Longer travel distance was associated with higher emergency medical services use
      (odds ratio 1.09, 95% confidence interval 1.09-1.10), but it was not a predictor
      of clinical events. After adjustment for covariates and inverse propensity score
      weighting, emergency medical services use was associated with a higher risk of 7
      day and 30-day clinical events. CONCLUSION: Several demographic and clinical
      features were associated with higher emergency medical services use including
      geographical variation. Although longer travel distance was shown to be linked to
      higher emergency medical services use, it was not an independent predictor of
      patient outcome. This has implications for the design of emergency medical
      services systems, triage and early diagnosis and treatment options.

PMID- 29652167
TI  - Computational phantoms, ICRP/ICRU, and further developments.
AB  - Phantoms simulating the human body play a central role in radiation dosimetry.
      The first computational body phantoms were based upon mathematical expressions
      describing idealised body organs. With the advent of more powerful computers in
      the 1980s, voxel phantoms have been developed. Being based on three-dimensional
      images of individuals, they offer a more realistic anatomy. Hence, the
      International Commission on Radiological Protection (ICRP) decided to construct
      voxel phantoms representative of the adult Reference Male and Reference Female
      for the update of organ dose coefficients. Further work on phantom development
      has focused on phantoms that combine the realism of patient-based voxel phantoms
      with the flexibility of mathematical phantoms, so-called 'boundary
      representation' (BREP) phantoms. This phantom type has been chosen for the ICRP
      family of paediatric reference phantoms. Due to the limited voxel resolution of
      the adult reference computational phantoms, smaller tissues, such as the lens of
      the eye, skin, and micron-thick target tissues in the respiratory and alimentary
      tract regions, could not be segmented properly. In this context, ICRP Committee 2
      initiated a research project with the goal of producing replicas of the ICRP
      Publication 110 phantoms in polygon mesh format, including all source and target
      regions, even those with micron resolution. BREP phantoms of the fetus and the
      pregnant female at various stages of gestation complete the phantoms available
      for radiation protection computations.

PMID- 29652168
TI  - Evidence for dose and dose rate effects in human and animal radiation studies.
AB  - For stochastic effects such as cancer, linear-quadratic models of dose are often
      used to extrapolate from the experience of the Japanese atomic bomb survivors to
      estimate risks from low doses and low dose rates. The low dose extrapolation
      factor (LDEF), which consists of the ratio of the low dose slope (as derived via
      fitting a linear-quadratic model) to the slope of the straight line fitted to a
      specific dose range, is used to derive the degree of overestimation (if LDEF > 1)
      or underestimation (if LDEF < 1) of low dose risk by linear extrapolation from
      effects at higher doses. Likewise, a dose rate extrapolation factor (DREF) can be
      defined, consisting of the ratio of the low dose slopes at high and low dose
      rates. This paper reviews a variety of human and animal data for cancer and non
      cancer endpoints to assess evidence for curvature in the dose response (i.e.
      LDEF) and modifications of the dose response by dose rate (i.e. DREF). The JANUS
      mouse data imply that LDEF is approximately 0.2-0.8 and DREF is approximately 1.2
      2.3 for many tumours following gamma exposure, with corresponding figures of
      approximately 0.1-0.9 and 0.0-0.2 following neutron exposure. This paper also
      cursorily reviews human data which allow direct estimates of low dose and low
      dose rate risk.

PMID- 29652169
TI  - Contribution of Neuromuscular Factors to Quadriceps Asymmetry After Anterior
      Cruciate Ligament Reconstruction.
AB  - CONTEXT:   To quantify quadriceps weakness after anterior cruciate ligament
      reconstruction (ACLR), researchers have often analyzed only peak torque. However,
      analyzing other characteristics of the waveform, such as the rate of torque
      development (RTD), time to peak torque (TTP), and central activation ratio (CAR),
      can lend insight into the underlying neuromuscular factors that regulate torque
      development. OBJECTIVE:   To determine if interlimb neuromuscular asymmetry was
      present in patients with ACLR at the time of clearance to return to activity.
      DESIGN:   Cross-sectional study. SETTING:   Laboratory. PATIENTS OR OTHER
      PARTICIPANTS:   A total of 10 individuals serving as controls (6 men, 4 women;
      age = 23.50 +/- 3.44 years, height = 1.73 +/- 0.09 m, mass = 71.79 +/- 9.91 kg)
      and 67 patients with ACLR (43 men, 24 women; age = 21.34 +/- 5.73 years, height =
      1.74 +/- 0.11 m, mass = 77.85 +/- 16.03 kg, time postsurgery = 7.52 +/- 1.36
      months) participated. MAIN OUTCOME MEASURE(S):   Isokinetic (60 degrees /s) and
      isometric quadriceps strength were measured. Peak torque, TTP, and RTD were
      calculated across isometric and isokinetic trials, and CAR was calculated from
      the isometric trials via the superimposed burst. Repeated-measures analyses of
      variance were used to compare limbs in the ACLR and control groups. RESULTS:   No
      between-limbs differences were detected in the control group ( P > .05). In the
      ACLR group, the involved limb demonstrated a longer TTP for isokinetic strength (
      P = .04; Cohen d effect size [ES] = 0.18; 95% confidence interval [CI] = -0.16,
      0.52), lower RTD for isometric ( P < .001; Cohen d ES = 0.73; 95% CI = 0.38,
      1.08) and isokinetic ( P < .001; Cohen d ES = 0.84; 95% CI = 0.49, 1.19)
      strength, lower CAR ( P < .001; Cohen d ES = 0.37; 95% CI = 0.03, 0.71), and
      lower peak torque for isometric ( P < .001; Cohen d ES = 1.28; 95% CI = 0.91,
      1.65) and isokinetic ( P < .001; Cohen d ES = 1.15; 95% CI = 0.78, 1.52)
      strength. CONCLUSIONS:   Interlimb asymmetries at return to activity after ACLR
      appeared to be regulated by several underlying neuromuscular factors. We theorize
      that interlimb asymmetries in isometric and isokinetic quadriceps strength were
      associated with changes in muscle architecture. Reduced CAR, TTP, and RTD were
      also present, indicating a loss of motor-unit recruitment or decrease in firing
      rate.

PMID- 29652170
TI  - Pulmonary Transplantation of Human Induced Pluripotent Stem Cell-derived
      Macrophages Ameliorates Pulmonary Alveolar Proteinosis.
AB  - RATIONALE: Although the transplantation of induced pluripotent stem cell (iPSC)
      derived cells harbors enormous potential for the treatment of pulmonary diseases,
      in vivo data demonstrating clear therapeutic benefits of human iPSC-derived cells
      in lung disease models are missing. OBJECTIVES: We have tested the therapeutic
      potential of iPSC-derived macrophages in a humanized disease model of hereditary
      pulmonary alveolar proteinosis (PAP). Hereditary PAP is caused by a genetic
      defect of the GM-CSF (granulocyte-macrophage colony-stimulating factor) receptor,
      which leads to disturbed macrophage differentiation and protein/surfactant
      degradation in the lungs, subsequently resulting in severe respiratory
      insufficiency. METHODS: Macrophages derived from human iPSCs underwent
      intrapulmonary transplantation into humanized PAP mice, and engraftment, in vivo
      differentiation, and therapeutic efficacy of the transplanted cells were
      analyzed. MEASUREMENTS AND MAIN RESULTS: On intratracheal application, iPSC
      derived macrophages engrafted in the lungs of humanized PAP mice. After 2 months,
      transplanted cells displayed the typical morphology, surface markers,
      functionality, and transcription profile of primary human alveolar macrophages.
      Alveolar proteinosis was significantly reduced as demonstrated by diminished
      protein content and surfactant protein D levels, decreased turbidity of the BAL
      fluid, and reduced surfactant deposition in the lungs of transplanted mice.
      CONCLUSIONS: We here demonstrate for the first time that pulmonary
      transplantation of human iPSC-derived macrophages leads to pulmonary engraftment,
      their in situ differentiation to an alveolar macrophage phenotype, and a
      reduction of alveolar proteinosis in a humanized PAP model. To our knowledge,
      this finding presents the first proof-of-concept for the therapeutic potential of
      human iPSC-derived cells in a pulmonary disease and may have profound
      implications beyond the rare disease of PAP.

PMID- 29652171
TI  - Polarization-Dependent Atomic Force Microscopy-Infrared Spectroscopy (AFM-IR):
      Infrared Nanopolarimetric Analysis of Structure and Anisotropy of Thin Films and
      Surfaces.
AB  - Infrared techniques enable nondestructive and label-free studies of thin films
      with high chemical and structural contrast. In this work, we review recent
      progress and perspectives in the nanoscale analysis of anisotropic materials
      using an extended version of the atomic force microscopy-infrared (AFM-IR)
      technique. This advanced photothermal technique, includes polarization control of
      the incoming light and bridges the gap in IR spectroscopic analysis of local
      anisotropic material properties. Such local anisotropy occurs in a wide range of
      materials during molecular nucleation, aggregation, and crystallization
      processes. However, analysis of the anisotropy in morphology and structure can be
      experimentally and theoretically demanding as it is related to order and disorder
      processes in ranges from nanoscopic to macroscopic length scales, depending on
      preparation and environmental conditions. In this context IR techniques can
      significantly assist as IR spectra can be interpreted in the framework of optical
      models and numerical calculations with respect to both, the present chemical
      conditions as well as the micro- and nanostructure. With these extraordinary
      analytic possibilities, the advanced AFM-IR approach is an essential puzzle piece
      in direction to connect nanoscale and macroscale anisotropic thin film properties
      experimentally. In this review, we highlight the analytic possibilities of AFM-IR
      for studies on nanoscale anisotropy with a set of examples for polymer,
      plasmonic, and polaritonic films, as well as aggregates of large molecules and
      proteins.

PMID- 29652172
TI  - Air Pollution and Respiratory Infection: An Emerging and Troubling Association.

PMID- 29652173
TI  - A Review of Commercially Available Point-of-Care Devices to Concentrate Bone
      Marrow for the Treatment of Osteoarthritis and Focal Cartilage Lesions.
AB  - Objective Mesenchymal stem cells (MSCs) are a promising cell-based therapy
      treatment option for several orthopedic indications. Because culture expansion of
      MSC is time and cost intensive, a bedside concentration of bone marrow (BM)
      aspirate is used as an alternative. Many commercial systems are available but the
      available literature and knowledge regarding these systems is limited. We
      compared different point-of-care devices that concentrate BM (BMC) by focusing on
      technical features and quality parameters to help surgeons make informed
      decisions while selecting the appropriate device. Methods We compared published
      data on the BMC devices of Arteriocyte, Arthrex, Celling Biosciences, EmCyte,
      Exactech, ISTO Tech, Harvest Tech/Terumo BCT, and Zimmer/BIOMET regarding
      technical features (centrifugation speed/time, input/output volume, kit
      components, type of aspiration syringes, filter usage) and quality parameters of
      their final BMC product (hematocrit, concentration of platelets and total
      nucleated cells, concentration of MSC and connective tissue progenitor cells).
      Results The systems differ significantly in their technical features and
      centrifugation parameters. Only the fully automated systems use universal kits,
      which allow processing different volumes of BM. Only the Arthrex system allows
      selection of final hematocrit. There was no standardized reporting method to
      describe biologic potency. Conclusions Based on the data obtained in this review,
      recommending a single device is not possible because the reported data could not
      be compared between devices. A standardized reporting method is needed for valid
      comparisons. Furthermore, clinical outcomes are required to establish the true
      efficacy of these systems. We are conducting additional studies for more careful
      comparison among the devices.

PMID- 29652174
TI  - Short-Term Elevation of Fine Particulate Matter Air Pollution and Acute Lower
      Respiratory Infection.
AB  - RATIONALE: Nearly 60% of U.S. children live in counties with particulate matter
      less than or equal to 2.5 MUm in aerodynamic diameter (PM2.5) concentrations
      above air quality standards. Understanding the relationship between ambient air
      pollution exposure and health outcomes informs actions to reduce exposure and
      disease risk. OBJECTIVES: To evaluate the association between ambient PM2.5
      levels and healthcare encounters for acute lower respiratory infection (ALRI).
      METHODS: Using an observational case-crossover design, subjects (n = 146,397)
      were studied if they had an ALRI diagnosis and resided on Utah's Wasatch Front.
      PM2.5 air pollution concentrations were measured using community-based air
      quality monitors between 1999 and 2016. Odds ratios for ALRI healthcare
      encounters were calculated after stratification by ages 0-2, 3-17, and 18 or more
      years. MEASUREMENTS AND MAIN RESULTS: Approximately 77% (n = 112,467) of subjects
      were 0-2 years of age. The odds of ALRI encounter for these young children
      increased within 1 week of elevated PM2.5 and peaked after 3 weeks with a
      cumulative 28-day odds ratio of 1.15 per +10 MUg/m3 (95% confidence interval,
      1.12-1.19). ALRI encounters with diagnosed and laboratory-confirmed respiratory
      syncytial virus and influenza increased following elevated ambient PM2.5 levels.
      Similar elevated odds for ALRI were also observed for older children, although
      the number of events and precision of estimates were much lower. CONCLUSIONS: In
      this large sample of urban/suburban patients, short-term exposure to elevated
      PM2.5 air pollution was associated with greater healthcare use for ALRI in young
      children, older children, and adults. Further exploration is needed of causal
      interactions between PM2.5 and ALRI.

PMID- 29652175
TI  - The work programme of NERIS in post-accident recovery.
AB  - NERIS is the European platform on preparedness for nuclear and radiological
      emergency response and recovery. Created in 2010 with 57 organisations from 28
      different countries, the objectives of the platform are to: improve the
      effectiveness and coherency of current approaches to preparedness; identify
      further development needs; improve 'know how' and technical expertise; and
      establish a forum for dialogue and methodological development. The NERIS
      Strategic Research Agenda is now structured with three main challenges: (i)
      radiological impact assessments during all phases of nuclear and radiological
      events; (ii) countermeasures and countermeasure strategies in emergency and
      recovery, decision support, and disaster informatics; and (iii) setting up a
      multi-faceted framework for preparedness for emergency response and recovery. The
      Fukushima accident has highlighted some key issues for further consideration in
      NERIS research activities, including: the importance of transparency of decision
      making processes at local, regional, and national levels; the key role of access
      to environmental monitoring; the importance of dealing with uncertainties in
      assessment and management of the different phases of the accident; the use of
      modern social media in the exchange of information; the role of stakeholder
      involvement processes in both emergency and recovery situations; considerations
      of societal, ethical, and economic aspects; and the reinforcement of education
      and training for various actors. This paper emphasises the main issues at stake
      for NERIS for post-accident management.

PMID- 29652176
TI  - Medication Use in Women and Men With Sudden Unexpected Death.
AB  - BACKGROUND: In Wake County, NC, sudden unexpected death accounts for 10% to 15%
      of all natural deaths in individuals 18 to 64 years old. Medications such as
      aspirin, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers,
      statins, and beta-blockers are recommended in guidelines to reduce cardiovascular
      events and even sudden death (beta-blockers). However, guidelines are often
      underpracticed, even in high-risk patients, with noted disparities in women.
      OBJECTIVE: We assessed the relation between prescription of evidence-based
      medications and sudden unexpected death in Wake County, NC. METHODS: We analyzed
      399 cases of sudden unexpected death for the time period March 1, 2013 to
      February 28, 2015 in Wake County, NC. Medications were assessed from available
      medical examiner reports and medical records and grouped using the third level of
      the Anatomical Therapeutic Chemical Classification System (ATC) codes. This study
      was reviewed and exempt by the University of North Carolina's institutional
      review board. RESULTS: Among 126 female and 273 male victims, women were
      prescribed more medications overall than men (6.5 vs 4.3, P = 0.001); however,
      the use of guideline-directed therapies was not different between genders in the
      chronic conditions associated with sudden death. Overall, there was remarkably
      low use of evidence-based medications. CONCLUSIONS: Our findings highlight the
      need to improve prescribing of evidence-based medications and to further explore
      the relationship between undertreatment and sudden unexpected death.

PMID- 29652177
TI  - Bronchial Epithelial IgA Secretion Is Impaired in Asthma. Role of IL-4/IL-13.
AB  - RATIONALE: Asthma is associated with increased lung IgE production, but whether
      the secretory IgA system is affected in this disease remains unknown. OBJECTIVES:
      We explored mucosal IgA transport in human asthma and its potential regulation by
      T-helper cell type 2 inflammation. METHODS: Bronchial biopsies from asthma and
      control subjects were assayed for bronchial epithelial polymeric immunoglobulin
      receptor (pIgR) expression and correlated to T-helper cell type 2 biomarkers.
      Bronchial epithelium reconstituted in vitro from these subjects, on culture in
      air-liquid interface, was assayed for pIgR expression and regulation by IL-4/IL
      13. MEASUREMENTS AND MAIN RESULTS: Downregulation of pIgR protein was observed in
      the bronchial epithelium from patients with asthma (P = 0.0002 vs. control
      subjects). This epithelial defect was not observed ex vivo in the cultured
      epithelium from patients with asthma. Exogenous IL-13 and IL-4 could inhibit pIgR
      expression and IgA transcytosis. Mechanistic experiments showed that autocrine
      transforming growth factor-beta mediates the IL-4/IL-13 effect on the pIgR, with
      a partial contribution of upregulated transforming growth factor-alpha/epidermal
      growth factor receptor. CONCLUSIONS: This study shows impaired bronchial
      epithelial pIgR expression in asthma, presumably affecting secretory IgA-mediated
      frontline defense as a result of type 2 immune activation of the transforming
      growth factor pathway.

PMID- 29652178
TI  - Multi-modal imaging for dose planning and its benefits: the paradigm of head and
      neck tumours.
AB  - The ultimate goal of any radiotherapy is to eradicate the disease without
      inflicting damage on the normal tissues surrounding the tumours, which could be
      responsible for late treatment morbidity. To achieve this objective, the first
      step is to precisely select and delineate the target volumes to which a given
      dose will be prescribed. This step requires the use of multi-modal images from
      clinical examination to anatomical and molecular images. Imaging examination will
      be used not only to delineate the boundaries of the tumour volume, but also to
      assess tumour heterogeneity and, possibly, to guide a heterogeneous dose
      prescription (i.e. the so-called 'dose painting' approach). Last, re-imaging the
      patient during treatment to assess variation of the tumour volume during
      radiotherapy may also be performed in the framework of adaptive treatment. Over
      the last decade, a lot of information has been gathered on the use of multi-modal
      imaging for dose planning, and its potential and technical difficulties have been
      identified. During the lecture, the speaker will review the state-of-the-art of
      multi-imaging for treatment, using head and neck tumours as a paradigm,
      emphasising what should be considered as routine practice and what should still
      be viewed as research questions. (c) 2018 ICRP. Published by SAGE.

PMID- 29652179
TI  - Associations Between Maternal Nutrition Knowledge, Attitude, and Practice and 25
      Hydroxyvitamin D Levels and Rickets in Children in Xinjiang Province, People's
      Republic of China.
AB  - We explored the association between maternal nutrition knowledge, attitude, and
      practice (KAP) and 25-hydroxyvitamin D (25(OH)D) values in children with rickets
      in Xinjiang, People's Republic of China. We recruited 514 mothers with children
      (<2 years) from pediatric outpatient departments. We determined general status of
      families, maternal nutrition KAP, and 25(OH)D values in 212 children with
      rickets, with doctors using "Prevention and Treatment Program for Infant and
      Young Children Rickets" and "Application Guideline for Vitamin D and Bone Health
      in Adult Chinese (2014 Standard Edition)" to identify. We then assessed the
      associations between nutrition KAP and 25(OH)D values. The 25(OH)D values were
      positively correlated with maternal nutrition KAP scores. Factors influencing
      rickets included per-capita monthly dietary expenditure and spousal education
      level. Factors associated with nutrition practice included maternal education
      level, gestational vitamin D level, and nutrition knowledge. Augmented maternal
      nutrition KAP may improve 25(OH)D levels in children with rickets to a normal
      range.

PMID- 29652180
TI  - Evidence-Based Management of In-Toeing in Children.

PMID- 29652181
TI  - Trends and Substance Use Associations With E-Cigarette Use in US Adolescents.
AB  - Concerns exist that e-cigarette use may introduce adolescents to drugs. This
      study explores trends and associations of inhaled tobacco use with drug use. We
      performed a secondary data analysis on the National Youth Risk Behavior Survey
      examining the inhaled tobacco and drug use patterns among US teens. Adjusted odds
      ratios were calculated using bivariate and multivariate analyses between inhaled
      tobacco use with other drug use, adjusting for age, race/ethnicity, and gender.
      When adjusting for gender, age, and race/ethnicity, teens who use only e
      cigarettes had a higher odds than peers who do not use any inhaled tobacco
      products to have ever tried marijuana or alcohol, currently use marijuana or
      alcohol, have lifetime drug use, and misused prescription medications. Drug risk
      behavior appears stratified with type of inhaled tobacco used, with generally
      exclusive e-cigarette use linked to lowest risk and conventional and e-cigarette
      use associated with highest risk of drug use.

PMID- 29652182
TI  - Risk assessment practice within primary mental health care: A logics perspective.
AB  - From the 1980s onwards, discourses of risk have continued to grow, almost in
      ubiquity. Ideas and practices of risk and risk aversion have extended to UK
      mental health care where services are expected to assess and manage risks, and
      high-quality clinical assessment has been revised to incorporate risk assessment.
      This article problematises practices of risk assessment in mental health
      provision, focussing on the base-rate problem. It presents an analysis of audio
      recordings of risk assessments completed within a primary care mental health
      service. The analysis is informed by a critical logics approach which, using
      ideas from discourse theory as well as Lacanian psychoanalysis, involves
      developing a set of logics to describe, analyse and explain social phenomena. We
      characterise the assessments as functioning according to social logics of well
      oiled administration and preservation, whereby bureaucratic processes are
      prioritised, contingency ironed out or ignored, and a need to manage potential
      risks to the service are the dominant operational frames. These logics are
      considered in terms of their beatific and horrific fantasmatic dimensions,
      whereby risk assessment is enacted as infallible (beatific) until clients become
      threats (horrific), creating a range of potential false negatives, false
      positives and so forth. These processes function to obscure or background
      problems with risk assessment, by generating practices that favour and offer
      protection to assessors, at the expense of those being assessed, thus presenting
      a challenge to the stated aim of risk assessment practice.

PMID- 29652183
TI  - Effects of sunitinib on immunoreactivity of vimentin, E-cadherin and S100 in
      kidneys of streptozotocin induced diabetic mice.
AB  - Diabetes mellitus (DM) affects many organs including kidney. Tyrosine kinase can
      cause hypoglycemia and sunitinib is an inhibitor of tyrosine kinase. We
      investigated the possible effects of sunitinib on the kidney of streptozotocin
      (STZ) induced type 1 diabetic mice. We used 28 CD 1 type male mice divided into
      four groups of seven. Type 1 diabetes was induced by injection of STZ. Group 1
      was the untreated control. Group 2 comprised non-diabetic mice + sunitinib. Both
      groups 1 and 2 exhibited normal blood glucose levels. Group 3 comprised STZ
      treated diabetic mice + saline. Group 4 were diabetic mice + sunitinib treatment.
      Kidneys were removed after 8 weeks. The immunoreactivities of vimentin, E
      cadherin and S100 were assessed. Immunostaining of vimentin, E-cadherin and S100
      was located in both the glomeruli and tubules of the kidney. We found that the
      number of vimentin and E-cadherin positive glomeruli and tubules were increased
      after sunitinib treatment compared to saline treated diabetic mice. The number of
      vimentin labeled tubules was decreased in the sunitinib treated group compared to
      diabetic + saline groups. Differences in the number of S100 positive tubules and
      glomeruli between groups 3 and 4 were not statistically significant. The effect
      of sunitinib on experimental diabetic mice appears to be related to levels of
      vimentin, E-cadherin and S100 in the glomeruli and tubules of the kidney, and
      sunitinib may protect against renal damage from DM.

PMID- 29652184
TI  - Dioxin-like Compounds in Lake Fish Species: Evaluation by DR-CALUX Bioassay.
AB  - Fish consumption is the principal source of intake of organochlorinated compounds
      in humans. Compared with other types of foods of animal origin, fish contain the
      highest levels of polychlorinated biphenyls (PCBs), polychlorinated dibenzo- p
      dioxins, and polychlorinated dibenzofurans, all of which are classified as highly
      toxic organochlorine compounds. Currently, lakes and fish farms in northern Italy
      are not regularly monitored for PCBs and dioxins in areas contaminated by
      industrial sources, partially because of the high costs of traditional analytical
      methods that limit the number of samples to be analyzed. The DR-CALUX cell
      bioassay is based on the uptake of the cellular aryl hydrocarbon receptor (AhR)
      for dioxins and dioxin-like compounds. The aim of this study was to assess the
      levels of dioxins and dioxin-like PCB contamination in Lake Maggiore and Lake
      Como, two lakes in northwestern Italy, and in nearby areas. The levels were
      quantified using the cell bioassay DR-CALUX and reference controls in two wild
      fish species, perch ( Perca fluviatilis) and roach ( Rutilus rutilus), and in a
      farmed species, rainbow trout ( Oncorhynchus mykiss). Tissue samples collected
      from the farmed rainbow trout were also submitted to immunohistochemical analysis
      of CYP1A expression as a marker for environmental pollutant-induced liver damage.
      The levels of dioxins, furans, and dioxin-like PCBs were all below the maximum
      levels and action limits set by European Union Regulation, suggesting no risk for
      human health associated with the consumption of the fish species caught or farmed
      in these areas.

PMID- 29652185
TI  - The a' velocity in the tissue Doppler predicts S/D ratio <1 in patients with a
      normal ejection fraction.
AB  - OBJECTIVES: To compare the ability of the a' velocity and the e' velocity in
      predicting a dominant diastolic pulmonary vein flow (S/D ratio <1) in patients
      with normal ejection fraction. DESIGN: We retrospectively evaluated the diastolic
      function according to the ASE/EACVI guidelines, the S/D ratio and the septal,
      lateral and average a' velocity in 293 unselected in-hospital patients, aged 39
      86 years, in sinus rhythm and with no or mild valve disease, having a normal
      systolic function (EF >50%). RESULTS: There was a good linear correlation between
      the S/D ratio and the a' velocity, but a tendency towards a negative correlation
      between the S/D ratio and the e' velocity. S/D ratio <1 was seen in 43 patients.
      These patients had a significantly lower a' velocity compared to those with S/D
      ratio >=1, septal (6,1 +/- 2,4 v 8,8 +/- 2,1 cm/s; p < .001) and lateral (6,0 +/-
      2,6 v 9,3 +/- 2,5 cm/s; p < .001) No significant difference was seen in the
      septal e' velocity (6,8 +/- 2,4 v 6,8 +/- 2,1 cm/s), lateral e' velocity (9,4 +/-
      2,6 v 9,1 +/- 2,8 cm/s) or in the ejection fraction (58,6 +/- 4,4% v 58,7 +/-
      4,0%). A diastolic dysfunction was present in 62 patients, normal diastolic
      function in 231 patients. The a' velocity was significantly lower in patients
      with S/D ratio <1 in both groups (p < .01). CONCLUSION: The a' velocity is
      superior to the e' velocity in predicting S/D ratio <1 in patients with normal
      ejection fraction regardless the ASE/EACVI diastolic classification. A failing
      left atrium seems to be the explanation.

PMID- 29652186
TI  - Surgical Treatment of Mild to Severe Hallux Valgus Deformities With a
      Percutaneous Subcapital Osteotomy Combined With a Lateral Soft Tissue Procedure.
AB  - : Distal metatarsal (MT) osteotomies have been used in mild or moderate cases of
      hallux valgus (HV) and proximal MT osteotomy has been considered the treatment of
      choice for severe deformities. A distal osteotomy could achieve a greater degree
      of correction by the addition of a distal soft-tissue procedure and be used to
      treat also severe deformity. Limited evidence about the use of the percutaneous
      subcapital osteotomy (SCOT); a type of MT osteotomy, in combination of a soft
      tissue procedure, is available. We evaluated this procedure routinely used in our
      clinic. A total of 30 consecutive patients treated in our hospital from September
      2012 to April 2015 with SCOT combined with lateral soft tissue release were
      included in this retrospective review. Outcomes assessed included radiological
      parameters: HV angle (HVA) and intermetatarsal angle (IMA), clinical evaluation
      using the American Orthopaedic Foot and Ankle Society (AOFAS) score, and
      complication rate. In 12 of the 30 patients included, the pathology was
      bilateral, comprising a total of 42 cases. The overall correction of the angles
      was statistically significant (P < .001), changing from a HVA of 28.2 degrees 
      and IMA of 13.5 degrees  preoperatively to 8.0 degrees  and 6.0 degrees 
      postoperatively, respectively. The cases were divided into mild-moderate (34/42)
      and severe (8/42). Both groups showed a statistically significant correction in
      the angles, 3 months after surgery (P < .001). The AOFAS score showed a median of
      49 points (n = 24) preoperatively and of 95 points (n = 40) at the end of follow
      up. The complication rate at end of follow-up was 19% (8/42). After a minimum
      follow-up of 1 year, our technique for HV correction results in a clinically
      relevant improvement of the radiological parameters and AOFAS score in mild to
      severe deformities. Combination with lateral release could be a meaningful
      surgical alternative for the treatment of severe cases to help decrease the risk
      of recurrence. LEVELS OF EVIDENCE: Level IV.

PMID- 29652187
TI  - Blood Transfusion During Total Ankle Arthroplasty Is Associated With Increased In
      Hospital Complications and Costs.
AB  - INTRODUCTION: Total ankle arthroplasty (TAA) is an increasingly used, effective
      treatment for end-stage ankle arthritis. Although numerous studies have
      associated blood transfusion with complications following hip and knee
      arthroplasty, its effects following TAA are largely unknown. This study uses data
      from a large, nationally representative database to estimate the association
      between blood transfusion and inpatient complications and hospital costs
      following TAA. METHODS: Using the Nationwide Inpatient Sample (NIS) database from
      2004 to 2014, 25 412 patients who underwent TAA were identified, with 286 (1.1%)
      receiving a blood transfusion. Univariate analysis assessed patient and hospital
      factors associated with blood transfusion following TAA. RESULTS: Patients
      requiring blood transfusion were more likely to be female, African American,
      Medicare recipients, and treated in nonteaching hospitals. Average length of stay
      for patients following transfusion was 3.0 days longer, while average inpatient
      cost was increased by approximately 50%. Patients who received blood transfusion
      were significantly more likely to suffer from congestive heart failure,
      peripheral vascular disease, hypothyroidism, coagulation disorder, or anemia.
      Acute renal failure was significantly more common among patients receiving blood
      transfusion ( P < .001). CONCLUSION: Blood transfusions following TAA are
      infrequent and are associated with multiple medical comorbidities, increased
      complications, longer hospital stays, and increased overall cost. LEVELS OF
      EVIDENCE: Level III: Retrospective, comparative study.

PMID- 29652188
TI  - Serum concentrations of apelin-17 isoform vary in accordance to blood pressure
      categories in individuals with obesity class 3.
AB  - BACKGROUND: The aim of this study was to investigate if serum concentrations of
      apelin-36, apelin-17, apelin-13 or apelin-12 were different in obesity class 3
      individuals with hypertension, when compared to those without hypertension
      (normal or high-normal). SUBJECTS AND METHODS: Twenty six individuals with
      obesity class 3-related hypertension and thirty three individuals without
      hypertension, who were divided in individuals with normal (n = 23) or with high
      normal (n = 10) blood pressure (BP) were analyzed. All individuals presented
      obesity class 3, without diabetes mellitus. Measurements of all apelin isoforms
      were performed using enzyme-linked immunosorbent assay kits. Analysis of
      differences between groups of Apelin isoform concentrations was performed by a
      One-way ANOVA, with a Tukey test post hoc. RESULTS: The individuals of the
      hypertensive group presented a slightly lower serum concentration of all apelin
      isoforms, but these differences were not statistically significant. These results
      were more evident when the group of patients without hypertension were divided
      based in normal and high-normal BP, observing that apelin-17 isoform were higher
      in individuals with high-normal BP in comparison to subjects with normal BP (P =
      0.018); concentrations were also higher when compared to subjects with
      hypertension (P = 0.004). CONCLUSIONS: To our knowledge, this is the first study
      regarding the differences of apelin-17 isoform concentrations in individuals
      pertaining to different categories of BP, who presented obesity class 3. The
      group of patients that presented hypertension showed a lower concentration of all
      isoforms. This observation could be due to the fact that these patients were
      taking antihypertensive medication.

PMID- 29652189
TI  - A Review and Update on Papillary Immature Metaplasia of the Uterine Cervix: A
      Distinct Subset of Low-Grade Squamous Intraepithelial Lesion, Proposing a
      Possible Cell of Origin.
AB  - CONTEXT: - Papillary immature metaplasia (PIM) is a known papillary cervical
      lesion associated with low-risk human papillomavirus (LR-HPV). OBJECTIVE: - To
      evaluate additional clinicopathologic features and the HPV genotypes of PIM and
      discuss the presumptive cell of origin. DESIGN: - A total of 26 PIM cases were
      evaluated by p16INK4a, cytokeratin (CK) 7, and CK17 immunohistochemical
      stainings. Human papillomavirus genotyping was performed, by using HPV DNA Chip,
      HPV polymerase chain reaction (PCR), and real-time PCR. RESULTS: -
      Histologically, PIM forms either a papillary mass (n = 21 of 26, 81%) or a
      slightly elevated/flat plaque (n = 5, 19%). All cases contain variable amounts of
      mucinous epithelia within the lesions. Koilocytosis was identified in 15 of the
      26 cases (58%). Sixteen cases (61%) were associated with LR-HPV (types 6, 11, or
      42), but 3 cases (12%) with high-risk (HR) HPV (16, 16/18, and 33), 2 cases (8%)
      with mixed LR- and HR-HPV (6/16 and 11/58), while 2 cases (8%) were negative, but
      p16INK4a immunostaining showed nonblock positivity in all cases. Eight (31%) had
      high-grade squamous intraepithelial lesion (HSIL) in the adjacent mucosa, 4 (50%)
      of which showed direct continuity. Identical HPV subtypes were confirmed in
      separately microdissected cases from PIM and adjacent HSIL. Most lesions (n = 24,
      92%) expressed CK17 (reserve cell marker) in a bottom-heavy pattern and CK7
      (squamocolumnar junction [SCJ] marker) in a top-heavy pattern, while most cases
      of low-grade squamous intraepithelial lesion (LSIL) were negative for both
      markers. CONCLUSIONS: - Our results suggest that PIM is a distinct subset of LSIL
      showing a productive HPV infection, but PIM involves the transformation zone and
      is proximal to SCJ, while LSIL is mostly from ectocervix or distal to the SCJ.

PMID- 29652190
TI  - Anal Cytology: Institutional Statistics, Correlation With Histology, and
      Development of Multidisciplinary Screening Program With Review of the Current
      Literature.
AB  - CONTEXT: - The incidence of anal cancer in the United States is on the rise in
      high-risk populations. The anal Papanicolaou test (APT) is advocated as a
      screening tool, in addition to digital rectal examination and high-resolution
      anoscopy. OBJECTIVE: - To review our experience and the current literature to
      create, in cooperation with clinicians, a standardized screening and treatment
      algorithm given our large volume of APTs. DATA SOURCES: - All APTs collected
      between January 2013 and June 2015 were reviewed and correlated with follow
      up/concurrent biopsy diagnoses, and clinical and social history. In total, 1417
      APTs were performed on 1185 patients and APT results were as follows: 17.4% (247
      of 1417) unsatisfactory; 27.9% (395 of 1417) negative; 19.5% (276 of 1417)
      atypical squamous cells of undetermined significance (ASC-US); 24.1% (342 of
      1417) low-grade squamous intraepithelial lesion (LSIL); 3.6% (51 of 1417)
      atypical squamous cells, cannot exclude high-grade squamous intraepithelial
      lesion (HSIL) (ASC-H); and 7.5% (106 of 1417) HSIL. In total 376 cases (26.5%)
      had concurrent/follow-up biopsy. Review of all unsatisfactory cases with squamous
      intraepithelial lesion (SIL) on biopsy showed LSIL in 19.2% (5 of 26). Anal
      Papanicolaou test with cytologic abnormality (ASC-US+) had an 83.8% (315 of 376)
      rate of biopsy-proven disease, and sensitivity was higher (92%) for high-grade
      anal intraepithelial neoplasia or worse (AIN2+). Overall detection of AIN2+ using
      ASC-US+ showed specificity of 26%, negative predictive value of 92%, and positive
      predictive value of 26%. CONCLUSIONS: - Anal cytology has a high abnormal rate
      (54.7%) and sensitivity but poor correlation with histologic grade. High
      unsatisfactory rate indicates need for improvement in sampling with 68.4% of
      cases having SIL on biopsy. Multidisciplinary effort led to improvements in
      sampling, cytologic interpretation, and development of a standardized management
      algorithm.

PMID- 29652191
TI  - Evaluation and Significance of Mortise Instability in Supination External
      Rotation Fibula Fractures: A Review Article.
AB  - : Evaluation and management of ankle fractures has progressed in parallel to an
      evolving understanding of ankle stability. While stability of the mortise had
      historically been attributed to the lateral malleolus, Lauge-Hansen's
      contributions followed by multiple other investigations increased the emphasis on
      the significance of medial-sided injury in destabilizing the mortise. As the
      importance of the deltoid ligament has been elucidated, the means of assessing
      ligamentous incompetence and the prognostic significance of an unstable mortise
      continue to be defined. LEVEL OF EVIDENCE: Level V, expert opinion.

PMID- 29652192
TI  - Achilles Pullout Strength After Open Calcaneoplasty for Haglund's Syndrome.
AB  - BACKGROUND: Haglund's syndrome involves a prominent posterior superior prominence
      of the calcaneus. If nonoperative management fails, operative management with
      calcaneoplasty is often needed. No study has assessed Achilles tendon pullout
      strength after an open calcaneoplasty for Haglund's syndrome. The purpose of this
      study was to investigate those changes in a cadaveric model and provide objective
      data upon which to base postoperative recovery. METHODS: Seven matched pairs of
      cadaveric specimens (mid-tibia to toes) were divided into 2 cohorts: (1)
      intact/untreated and (2) open resection. The open resection group was treated
      with an open calcaneoplasty through a posterior approach using a microsagittal
      saw. We compared Achilles pullout strength between the 2 groups through the use
      of a mechanical testing system. Specimens were then loaded to failure. Lateral
      radiographs were obtained before and after surgery to quantify bone removal.
      Outcome measures included height of bony resection, angle of bone resection, and
      load to failure. RESULTS: The mean maximum pullout strength was significantly
      higher in the intact specimens (1300 +/- 500 N) compared to the open resection
      group (740 +/- 180 N) ( P < .01), representing a 45% reduction in pullout force
      in the open resection group. Pullout force was significantly correlated to bone
      mineral density (BMD) ( P < .05). Pullout force was negatively correlated to both
      radiographic measures of resection level, angle, and height, but neither of these
      were significant. CONCLUSION: Open calcaneoplasty demonstrated a significant
      weakness of the Achilles tendon insertion. Pullout strength of the Achilles was
      also positively correlated with BMD. CLINICAL RELEVANCE: Biomechanical evidence
      presented above supports the practice of protected weightbearing and cautious
      return to activity after open calcaneoplasty for Haglund's syndrome.

PMID- 29652193
TI  - Relationship Between Bone Marrow Lesions on MRI and Cartilage Degeneration in
      Osteochondral Lesions of the Talar Dome.
AB  - BACKGROUND: In the evaluation of osteochondral lesions of the talar dome (OLT),
      bone marrow lesions (BML) are commonly observed in the subchondral bone on
      magnetic resonance imaging (MRI). However, the significance of BML, such as the
      histology of the overlying cartilage, is still unclear. The purpose of this study
      was to investigate the relationship between the BML and cartilage degeneration in
      OLT. METHODS: Thirty-three ankles with OLT were included in this study. All
      ankles underwent CT and MRI and had operative treatment. The ankles were divided
      into 2 groups, depending on the presence of bone sclerosis (ie, with or without)
      in the host bone just below the osteochondral fragment (nonsclerosis group and
      sclerosis group). The area of BML was compared between the 2 groups. Biopsies of
      the osteochondral fragment from 20 ankles were performed during surgery, and the
      correlation between the BML and cartilage degeneration was analyzed. The
      remaining 13 ankles had the CT and MRI compared with the arthroscopic findings.
      RESULTS: The mean area of BML in the nonsclerosis group was significantly larger
      than that in the sclerosis group. In the histologic analysis, there was a
      significant and moderate correlation between the Mankin score and the area of
      BML. The mean Mankin score in the nonsclerosis group was significantly lower than
      that in the sclerosis group. CONCLUSIONS: This study revealed that a large area
      of BML on MRI exhibited low degeneration of cartilage of the osteochondral
      fragment, while a small area of BML indicated sclerosis of the subchondral bone
      with severe degeneration of cartilage. The evaluation of BML may predict the
      cartilage condition of the osteochondral fragment. LEVEL OF EVIDENCE: Level III,
      comparative series.

PMID- 29652194
TI  - Molecular docking revealed the binding of nucleotide/side inhibitors to Zika
      viral polymerase solved structures.
AB  - A new Zika virus (ZIKV) outbreak started in 2015. According to the World Health
      Organization, 84 countries confirmed ZIKV infection. RNA-dependent RNA polymerase
      (RdRp) was an appealing target for drug designers during the last two decades.
      Through molecular docking, we screened 16 nucleotide/side inhibitors against ZIKV
      RdRp. While the mode of interaction with ZIKV is different from that in the
      hepatitis C virus (HCV), nucleotide/side inhibitors in this study (mostly anti
      HCV) showed promising binding affinities (-6.2 to -9.7 kcal/mol calculated by
      AutoDock Vina) to ZIKV RdRp. Setrobuvir, YAK and, to a lesser extent, IDX-184
      reveal promising results compared to other inhibitors in terms of binding ZIKV
      RdRp. These candidates would be powerful anti-ZIKV drugs.

PMID- 29652195
TI  - A Meta-Analysis of Major Foodborne Pathogens in Chinese Food Commodities Between
      2006 and 2016.
AB  - Prevalence of pathogenic bacteria in food commodities in China have been reported
      in numerous publications over time. However, the results are scattered and
      varied. To calculate a robust point estimate with a higher statistical power, we
      applied meta-analytic approach for investigating the prevalence of common
      foodborne pathogens in major food items in China. Data, on prevalence of bacteria
      in various food commodities were extracted and analyzed from 361 (132 English and
      229 Chinese) publications. Prevalence of eight most frequently reported pathogens
      on six broad food categories was used for pooled and subgroup meta-analysis by
      DerSimonian-Laird method in random-effects model. The estimated overall
      prevalence of pathogens in the foods was 8.5% (95% CI 8.2-8.7). The highest
      prevalence, irrespective of the pathogen type, was in the aquatic produce at
      12.8% (12.0-13.5), while the least was in the vegetables at 3.0% (2.6-3.4). Among
      the pathogens, the most prevalent was Vibrio at 21.3% (19.6-23.1), whereas the
      least was pathogenic Escherichia coli at 4.3% (3.3-5.2). The major food pathogens
      in Chinese foods in decreasing order of prevalence were Vibrio parahaemolyticus,
      Campylobacter, Bacillus cereus, Staphylococcus aureus, Salmonella, Enterobacter,
      Listeria monocytogenes, and pathogenic E. coli. Presence of these organisms in
      foods equates the risk of microbiological food safety in China with other
      developed countries rather than the developing countries. This justifies the need
      of novel perspectives for formulating policies on microbiological food safety and
      risk mitigation.

PMID- 29652196
TI  - Sleep and Performance.

PMID- 29652197
TI  - Relationship between locomotive syndrome and body composition among community
      dwelling middle-age and elderly individuals in Japan: The Yakumo study.
AB  - OBJECTIVES: Locomotive syndrome (LS) is a condition requiring nursing care for
      musculoskeletal disorders. Our aim was to evaluate the correlation between body
      composition, measured by bioelectrical impedance analysis (BIA), and LS, measured
      using the 25-question Geriatric Locomotive Functional Scale (GLFS-25). METHODS:
      We enrolled 286 individuals who were undergoing regular health follow-up. All
      individuals completed the GLFS-25, body composition analysis by BIA, and five
      physical performance tests related to LS: timed up-and-go test, 10-m gait time,
      maximum stride length, back strength, and grip strength. Measured variables and
      demographic data were compared between individuals with and without LS. RESULTS:
      The extracellular water ratio, the extracellular water/total body water (ECW/TBW)
      ratio differentiated the LS and non-LS groups (p=.005), with all physical
      function measures being lower among individuals with a high, compared to low,
      ECW/TBW ratio. The risk ratio for LS among individuals with a high ECW/TBW ratio
      was 2.31, with an odds ratio of 2.67. CONCLUSION: The ECW/TBW ratio is predictive
      of LS. Based on our results, we propose that BIA should routinely be performed,
      with follow-up and intervention, as needed, for individuals with a high ECW/TBW
      ratio, as they are at risk for developing LS.

PMID- 29652198
TI  - Efficacy and Safety of Mycophenolate Mofetil in the Treatment of Recalcitrant
      Intermediate Uveitis.
AB  - PURPOSE: To evaluate the efficacy and safety of mycophenolate mofetil (MMF) in
      the treatment of recalcitrant intermediate uveitis in a tertiary referral eye
      care center over a 1-year period. METHODS: Patients with at least three
      recurrences of intermediate uveitis per year, defined as relapse of disease after
      quiescent phase for >3 months after discontinuing all treatments and those with a
      minimum follow-up of 1 year, were analyzed retrospectively. MMF was initiated
      with oral steroids and the Standardization of Uveitis Nomenclature guidelines
      were used to evaluate patients at every visit. Response to treatment, worsening
      of uveitis, visual benefit, steroid withdrawal rates, and side-effect due to MMF
      were monitored. RESULTS: Data from 30 eyes of 19 patients were analyzed, of which
      10 were men and 11 has bilateral disease. The mean age of presentation was 32.6
      +/- 15.4 years and the commonest presenting complaints were floaters (26 eyes).
      The mean vitreous haze was 3+ at presentation and reduced to 0 at last follow-up
      (24 eyes). Out of the 30 eyes, 80% had complete resolution of vitreous haze at
      the end of one year. Worsening intermediate uveitis was seen in six eyes
      (15.78%). Steroid withdrawal was successful in 85% of eyes. Vision improved in
      56% of eyes. None of the patient developed serious systemic complications
      warranting withdrawal of MMF. CONCLUSION: MMF in our series was a safe and
      effective drug in controlling disease and preventing worsening in majority eyes
      with the most severe forms of intermediate uveitis. Larger studies are required
      before MMF is widely adopted for the management of recalcitrant intermediate
      uveitis.

PMID- 29652199
TI  - The Role and Mechanism of Borneol to Open the Blood-Brain Barrier.
AB  - BACKGROUND: The blood-brain barrier (BBB) is the greatest challenge in the
      treatment of intracranial malignant tumors. OBJECTIVE: The aim of this study is
      to determine the role of borneol in opening the BBB and elucidate the underlying
      mechanisms. MATERIALS AND METHODS: Twenty Sprague-Dawley (SD) rats were
      randomized into borneol group intragastrically administered with 10% borneol corn
      oil (2 mL/kg) and control group. After 30 minutes, 2% Evans blue (4 mL/kg) was
      injected. Thirty minutes later, brain tissue was analyzed using the Evans blue
      standard curve. Another 40 SD rats were randomized into high-, medium-, and low
      dose borneol groups and a control group. Each rat in the experimental groups was
      intragastrically administered with 10% borneol corn oil (2 mL/kg, 1.25 mL/kg, and
      0.5 mL/kg, respectively). The control group was injected with corn oil of 1.25
      mL/kg. After 30 minutes, the rats were killed, and the brain tissues were
      collected. The expression of occludin, occludens-1, nitric oxide synthase, P
      glycoprotein, and intercellular cell adhesion molecule-1 (ICAM-1) was detected by
      immunohistochemy. RESULTS: The concentration of Evans blue in the borneol group
      was higher than in the control group ( P < .05). The mean density of ICAM-1
      expression was higher in the experimental group than in the control group ( P <
      .05). In contrast, significant differences of positive area and total density of
      ICAM-1 were shown only between the high-dose group and the control group ( P <
      .05). CONCLUSION: Borneol can open the BBB, which might be related with the
      increased expression of ICAM-1.

PMID- 29652201
TI  - Trunk control and functionality in children with spastic cerebral palsy.
AB  - PURPOSE: To investigate the relationship between trunk control in sitting and
      functionality in children with spastic cerebral palsy (CP). METHODS: Fifty-eight
      children with spastic CP were included in the study. Functional abilities were
      evaluated with the Gross Motor Function Measurement-88 (GMFM-88) and the
      Pediatric Evaluation of Disability Inventory Functional Skills domain (PEDI-FSD).
      Trunk control in sitting was tested with the Trunk Control Measurement Scale
      (TCMS) and the Trunk Impairment Scale (TIS). The scores of the TCMS and TIS were
      compared with GMFM-88 and PEDI-FSD with Spearman correlation analysis. RESULTS:
      The total score of GMFM-88 was significantly correlated with the total score of
      TCMS (rho = 0.90, p < 0.01) and TIS (rho = 0.78, p < 0.01). The total score of
      PEDI-FSD was also significantly correlated with the total score of TCMS (rho =
      0.76, p < 0.01) and TIS (rho = 0.72, p < 0.01). CONCLUSIONS: The evaluation of
      trunk control can provide valuable information for functional abilities of
      children with spastic CP.

PMID- 29652200
TI  - Bursera copallifera Extracts Have Cytotoxic and Migration-Inhibitory Effects in
      Breast Cancer Cell Lines.
AB  - Plants from the Bursera genus are widely distributed in the tropical dry forests
      of Mexico. In traditional medicine, extracts from different species of Bursera
      have been used for a wide range of biological activities, including the treatment
      of cancer-related symptoms. Compounds present in the Bursera genus include
      lignans, flavonoids, steroids, short-chain aliphatic alkanes, acetates, alcohols,
      ketones, and terpenoids. In some instances, secondary metabolites of these
      classes of compounds may induce cytotoxicity, and therefore we sought to
      investigate the effects of B. copallifera leaf extracts in breast cancer cell
      lines to evaluate their potential therapeutic value for the treatment of breast
      cancer, one of the most prevalent types of cancer in women worldwide. Two B.
      copallifera leaf extracts exerted cytotoxic effects on both the MCF7 and MDA-MB
      231 breast cancer cell line models. The cytotoxic effect was more evident in the
      MDA-MB-231 triple negative cell line inhibiting also the migration of these
      cells. We identified hydroxycinnamic acid and flavonol derivatives as major
      phenolic components of the extracts. Our results strongly suggest a potential use
      of the Bursera leaf extracts rich in phenolic compounds, their individual
      phenolic compounds, or their combinations for the treatment of breast cancer.

PMID- 29652202
TI  - Effect of sulfasalazine use on the presence of Pneumocystis organisms in the lung
      among patients with rheumatoid arthritis: A test-negative design case-control
      study with PCR tests.
AB  - OBJECTIVE: To evaluate the effect of sulfasalazine (SSZ) on the presence of
      Pneumocystis jirovecii (P. jirovecii) in the lungs of rheumatoid arthritis (RA)
      patients. METHODS: We retrospectively studied episodes of suspected P. jirovecii
      pneumonia (PJP) which were examined for P. jirovecii with polymerase chain
      reaction (PCR). We employed a test negative design case-control study; the cases
      were episodes of suspected PJP that were positive for PCR, and the controls were
      episodes of suspected PJP that were negative for PCR. The odds ratio for the
      positive PCR result associated with SSZ use was estimated by Firth's logistic
      regression. RESULTS: Between 2003 and 2017, 36 cases and 83 controls were
      identified. While none of the cases received SSZ before the episode, 18 of the
      controls received the drug. In the primary analysis involving all the episodes,
      SSZ use was negatively associated with PCR positivity (adjusted odds ratio,
      0.087; confidence interval, <0.001-0.789). The sensitivity analysis, excluding
      those who received PJP prophylaxis, showed the same association as the primary
      analysis (adjusted odds ratio 0.085, 95% CI <0.001-0.790). CONCLUSION: This study
      demonstrated that SSZ use is associated with the absence of P. jirovecii in the
      lung, suggesting the preventive efficacy of the drug against PJP.

PMID- 29652203
TI  - Clinical Features of Toxocara-Seropositive Optic Neuritis in Korea.
AB  - PURPOSE: This study was undertaken to analyze the characteristics of optic
      neuritis in Korean patients seropositive for Toxocara. METHODS: We
      retrospectively reviewed data from patients diagnosed with optic neuritis and
      followed up for at least one month between 2012 and 2016. Patients were grouped
      according to Toxocara serological testing outcomes (positive or negative) and
      clinical characteristics were compared. RESULTS: The seropositive and
      seronegative groups comprised 13 and 12 patients, respectively. The seropositive
      patients were older (56.8 years versus 34.5 years), reported ocular pain less
      frequently (30.8% versus 91.7%), and showed more frequent asymmetric optic disc
      swelling (72.7% versus 22.2%). During follow-up, visual acuity of all
      seronegative patients improved to 20/40 or better, compared with 38.5% of the
      seropositive group. CONCLUSION: Atypical features such as painless, older age, or
      asymmetric disc swelling in optic neuritis may be related to seropositivity for
      Toxocara, suggesting the possibility of undiagnosed Toxocara optic neuropathy.

PMID- 29652204
TI  - Low-Dose Rituximab for Active Moderate-to-Severe Graves' Orbitopathy Resistant to
      Conventional Treatment.
AB  - PURPOSE: To report low-dose rituximab effect in Graves' orbitopathy (GO)
      resistant to conventional treatment. METHODS: Retrospective analysis of medical
      records, filled in according to the European Group on Graves' Orbitopathy
      (EUGOGO) standards, of patients with active moderate-to-severe GO who received
      low-dose rituximab after failure of conventional treatment. Efficacy was defined
      by a decrease of the clinical activity score of 2 points or <4/10. RESULTS: Among
      219 patients treated between 2012 and 2016 by pulse methylprednisolone, possibly
      followed by oral steroids and/or orbital radiotherapy, 15 (6.8%) finally received
      100 mg rituximab doses (cumulative dose, 100-400 mg) owing to persistent active
      disease. Rituximab showed efficacy within 2 months in 13 of 15 (87%), stable at 1
      year. No significant effect was observed on proptosis, lid fissure width, and eye
      motility. CONCLUSION: Low-dose rituximab showed sustained anti-inflammatory
      effect in most patients with active GO resistant to conventional treatment.

PMID- 29652205
TI  - Environmental impact of biogas: A short review of current knowledge.
AB  - The social acceptance of biogas is often hampered by environmental and health
      concerns. In this study, the current knowledge about the impact of biogas
      technology is presented and discussed. The survey reports the emission rate
      estimates of the main greenhouse gases (GHG), namely CO2, CH4 and N2O, according
      to several case studies conducted over the world. Direct emissions of gaseous
      pollutants are then discussed, with a focus on nitrogen oxides (NOx); evidences
      of the importance of suitable biomass and digestate storages are also reported.
      The current knowledge on the environmental impact induced by final use of
      digestate is critically discussed, considering both soil fertility and nitrogen
      release into atmosphere and groundwater; several case studies are reported,
      showing the importance of NH3 emissions with regards to secondary aerosol
      formation. The biogas upgrading to biomethane is also included in the study: with
      this regard, the methane slip in the off-gas can significantly reduce the
      environmental benefits.

PMID- 29652206
TI  - Posterior auricular muscle patch graft for exposed orbital implant.
AB  - The purpose of this article is to describe a surgical technique to repair an
      exposed orbital implant by posterior auricular muscle autograft. A retrospective
      review was conducted of four patients with an exposed orbital implant that were
      treated with a posterior auricular muscle graft. Four patients received posterior
      auricular muscle patch graft to the exposed orbital implant. The donor site
      healed with minimal scarring and remained well hidden. The graft incorporated
      fully into surrounding orbital tissue with no recurrent exposure at average of 13
      month follow-up. The posterior auricular muscle autograft is a viable technique
      for repairing an exposed orbital implant.

PMID- 29652207
TI  - A consecutive case series analysis of a behavioral intervention for enuresis in
      children with developmental disabilities.
AB  - Children with developmental disabilities (DD) are more likely than typically
      developing peers to have issues with enuresis. Past research has shown the
      success of behavioral treatments consisting of scheduled sits and reinforcement
      for continent voids. However, this research has included small sample sizes,
      while studies with larger numbers have lacked key information (i.e., baseline
      rates and follow-up data to evaluate maintenance and generalization). The current
      study conducted a consecutive case series analysis of 44 individuals with
      developmental disabilities who completed a 2-week program for enuresis. Results
      showed significant improvement in continent voids and follow-up data suggested
      positive results maintained when treatment was implemented by caregivers in a
      home environment.

PMID- 29652208
TI  - Age-based ultrasonographic criteria for diagnosis of autosomal dominant
      polycystic kidney disease in Persian cats.
AB  - Objectives The aim of this study was to establish ultrasound criteria for the
      diagnosis of autosomal dominant polycystic kidney disease (ADPKD) in Persian
      cats. Methods Eighty-two Persian cats were assessed using renal ultrasound and
      genotyped for the C->A transversion in exon 29 of PKD1. The animals were also
      submitted to hematological characterization, serum biochemistry analyses and
      urinalysis. Results Age, sex and neutering status did not differ between ADPKD (n
      = 12) and non-ADPKD (n = 70) cats. After integrated molecular
      genetics/ultrasonographic analysis, the presence of at least one renal cyst was
      sufficient to establish a diagnosis of ADPKD in animals up to 15 months of age.
      Two or more cysts were required for diagnosis in cats aged 16-32 months, and at
      least three cysts warranted diagnosis of ADPKD in animals aged 33-49 months.
      Finally, four or more cysts led to diagnosis in cats aged 50-66 months. Although
      cats with ADPKD exhibited higher serum calcium levels than non-affected cats,
      hematological, urinalysis and other biochemical parameters did not differ between
      the two groups. Conclusions and relevance Integrated analyses of imaging and
      molecular genetics data enabled, for the first time, the establishment of age
      based ultrasonographic criteria for the diagnosis of ADPKD in Persian cats. The
      development of imaging criteria is particularly relevant and useful in the
      clinical setting given the current limitations to access and the cost of
      molecular genetics-based diagnostic tests.

PMID- 29652209
TI  - Neurological outcome in children and youth with acquired brain injury 2-year post
      injury.
AB  - OBJECTIVE: To determine neurological outcome in children and youth with acquired
      brain injury (ABI) and explore associated factors. DESIGN: Cross-sectional study,
      two-years post-injury. PATIENTS: Hospital-based sample (n=112) aged 6-22 years.
      METHODS: Neurological outcome and participation were assessed with a
      multidimensional neurological examination and the Child and Adolescent Scale of
      Participation. Logistic regression analyses were used to explore the
      relationships. RESULTS: Both sensorimotor and cognitive deficits were found in 30
      31%, language deficits and behavioural deficits in 10-17%. Non-traumatic injury
      had a negative impact on neurological outcome, specifically regarding
      sensorimotor and language deficits. Lower education level showed a significantly
      poorer neurological outcome. High levels of age-expected participation were
      reported, with a significant relation between deficits and participation
      restrictions, especially at school. CONCLUSION: One out of three have a poor
      neurological outcome, related to type of injury and lower level of education. The
      amount of deficits is associated with participation restrictions.

PMID- 29652210
TI  - Idiopathic Central Nervous System Inflammatory Disease in the Setting of HLA-B27
      Uveitis.
AB  - PURPOSE: The purpose of the article is to describe a novel case of idiopathic
      central nervous system inflammatory disease with bilateral human leukocyte
      antigen (HLA)-B27-positive anterior uveitis. METHODS/RESULTS: A 15-year-old
      African American boy with bilateral HLA-B27-positive anterior uveitis controlled
      with topical and oral steroids for 8 months acutely developed headaches, left
      eyelid ptosis, and binocular diplopia. Imaging showed lesions in the right
      midbrain, superior colliculus, cerebellar peduncles, and cerebellar vermis and
      leptomeningeal enhancement along the vermian foliae. Cerebral spinal fluid tests
      showed mild lymphohistiocytic pleocytosis with negative cytology; inflammatory
      and infectious workup were negative. He received intravenous methylprednisolone
      without initial symptomatic improvement; repeat magnetic resonance imaging (MRI)
      showed reduced lesion burden. Oral steroids were continued; his symptoms resolved
      in 1 month. Repeat MRI 2 months after presentation showed almost complete lesion
      resolution. CONCLUSIONS: Chronic lymphocytic inflammation with pontine
      perivascular enhancement responsive to steroids (CLIPPERS) was diagnosed. HLA-B27
      positivity may represent a novel association with CLIPPERS.

PMID- 29652211
TI  - Simultaneous quantification by HPLC of purines in umami soup stock and evaluation
      of their effects on extracellular and intracellular purine metabolism.
AB  - Ribonucleotide flavor enhancers such as inosine monophosphate (IMP) and guanosine
      monophosphate (GMP) provide umami taste, similarly to glutamine. Japanese cuisine
      frequently uses soup stocks containing these nucleotides to enhance umami. We
      quantified 18 types of purines (nucleotides, nucleosides, and purine bases) in
      three soup stocks (chicken, consomme, and dried bonito soup). IMP was the most
      abundant purine in all umami soup stocks, followed by hypoxanthine, inosine, and
      GMP. The IMP content of dried bonito soup was the highest of the three soup
      stocks. We also evaluated the effects of these purines on extracellular and
      intracellular purine metabolism in HepG2 cells after adding each umami soup stock
      to the cells. An increase in inosine and hypoxanthine was evident 1 h and 4 h
      after soup stock addition, and a low amount of xanthine and guanosine was
      observed in the extracellular medium. The addition of chicken soup stock resulted
      in increased intracellular and extracellular levels of uric acid and guanosine.
      Purine metabolism may be affected by ingredients present in soups.

PMID- 29652212
TI  - Development of a normal tissue complication probability model for late
      unfavourable aesthetic outcome after breast-conserving therapy.
AB  - PURPOSE/OBJECTIVES: To develop a normal tissue complication probability (NTCP)
      model for late unfavourable aesthetic outcome (AO) after breast-conserving
      therapy. MATERIAL AND METHODS: The BCCT.core software evaluated the AO using
      standardized photographs of patients treated between 2009 and 2014. Dose maps in
      2 Gy equivalents were calculated assuming alpha/beta = 3.6 Gy. Uni- and
      multivariable logistic regression analysis was performed to study the predictive
      value of clinicopathological and dosimetric variables for unfavourable AO. The
      Lyman Kutcher Burman (LKB) model was fit to the data with dose modifying factors
      (dmf). Model performance was assessed with the area under the curve (AUC) of the
      receiver operating characteristic curve and bootstrap sampling. RESULTS: Forty
      four of the 121 analysed patients (36%) developed unfavourable AO. In the optimal
      multivariable logistic regression model, a larger breast volume receiving >=55 Gy
      (V55), a seroma and an axillary lymph node dissection (ALND) were independently
      associated with an unfavourable AO, AUC = 0.75 (95%CI 0.64;0.85). Beta-estimates
      were -2.68 for beta0, 0.057 for V55, 1.55 for seroma and 1.20 for ALND. The
      optimal LKB model parameters were EUD3.6(50) = 63.3 Gy, n = 1.00, m = 0.23,
      dmf(seroma) = 0.83 and dmf(ALND) = 0.84, AUC = 0.74 (95%CI 0.61;0.83).
      CONCLUSIONS: An NTCP model for late unfavourable AO after breast-conserving
      therapy was developed including seroma, axillary lymphadenectomy and V55.

PMID- 29652213
TI  - Ovarian reserve in young juvenile idiopathic arthritis patients.
AB  - OBJECTIVES: Juvenile idiopathic arthritis (JIA) occurs during reproductive age,
      however, there are no systematic data regarding ovarian function in this disease.
      METHODS: Twenty-eight post-pubertal JIA patients and age-matched 28 healthy
      controls were studied. Complete ovarian function was assessed during the early
      follicular phase of the menstrual cycle including anti-Mullerian hormone (AMH),
      estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and
      antral follicle count (AFC) by ovarian ultrasound, and anti-corpus lutheum
      antibodies (anti-CoL). Demographic data, menstrual abnormalities, disease
      parameters and treatment were also evaluated. RESULTS: The mean current age (22.6
      +/- 6.59 vs. 22.5 +/- 6.59 years, p = .952) was similar in JIA patients and
      healthy controls with a higher median menarche age [13(8-16) vs. 12(8-14) years,
      p = .029]. A lower median AMH levels [2.65(0.47-9.08) vs. 4.83(0.74-17.24) ng/mL,
      p = .029] with a higher LH [8.44 +/- 4.14 vs. 6.03 +/- 2.80 IU/L, p = .014] and
      estradiol levels [52.3(25.8-227.4) vs. 38.9(26.2-133.6) pg/mL, p = .008] were
      observed in JIA compared to control group. Anti-CoL and AFC were similar in both
      groups (p > .05). Further analysis of JIA patients revealed that current age,
      disease duration, number of active/limited joints, ESR, CRP, patient/physician
      VAS, JADAS 71, DAS 28, CHAQ, HAQ, patient/parents PedsQL, PF-SF 36, cumulative
      glucocorticoid and cumulative methotrexate doses were not correlated with AMH,
      FSH, estradiol levels or AFC (p > .05). CONCLUSION: The present study was the
      first to suggest diminished ovarian reserve, not associated to hypothalamic
      pituitary gonadal axis, in JIA patients during reproductive age. The impact of
      this dysfunction in future fertility of these patients needs to be evaluated in
      prospective studies.

PMID- 29652214
TI  - Staff Perceptions of Symptoms, Approaches to Assessment, and Challenges to
      Assessment Among Children With Cancer.
AB  - Nurses are often the first to recognize and respond to children's symptoms. This
      descriptive, exploratory study characterized how pediatric oncology health care
      providers characterize and assess children's cancer-related symptoms. The study
      also explored challenges associated with symptom assessment and information
      perceived as helpful in planning interventions. The setting was a Children's
      Oncology Group-affiliated hospital in the Intermountain West of the United
      States. Twenty-two pediatric oncology health care providers (95% female; 68%
      nurses) participated in one of four focus group sessions. Sessions were
      facilitated by two individuals and included six open-ended questions addressing
      participants' perspectives of cancer-related symptoms, approaches to symptom
      assessment, challenges and frustrations encountered when assessing symptoms, and
      information needed to plan interventions. Participants identified 75 physical and
      psychosocial responses that included both subjectively experienced symptoms and
      other consequences of the cancer experience. Qualitative content analysis
      procedures organized other responses into categories and subcategories.
      Participants most frequently reported using observational approaches including
      physical assessment findings and observation of the child's behavior to identify
      symptoms. Strategies that sought the child's input such as the use of a rating
      scale or seeking the child's verbal description were less frequently named.
      Participants related discerning and interpreting the child's behaviors as a
      challenge to symptom assessment. They also reported attention to symptom
      characteristics as important to planning interventions. Future directions include
      building capacity to support child-centric symptom assessment. Development of
      reliable and valid resources for use in clinical settings may support a more
      child-centric approach to symptom assessment.

PMID- 29652216
TI  - Psychophysiological measures of stress in caregivers of individuals with autism
      spectrum disorder: a systematic review.
AB  - PURPOSE: Parents of children with autism spectrum disorder (ASD) often self
      report heightened levels of stress and physical health problems. This paper
      reviewed studies assessing physiological measures of stress among parents of
      children with ASD. METHODS: Systematic database searches identified 15 studies
      meeting inclusion criteria. Studies were reviewed to determine: (a) control group
      characteristics; (b) caregiver and care recipient characteristics; (c) setting;
      (d) physiological measures employed; (e) physiological outcomes; and (f) stressor
      type. A measure of methodological quality was also applied. RESULTS: Salivary
      cortisol was the most common physiological measure employed. A pattern of blunted
      physiological activity emerged within the reviewed studies, though some studies
      reported normal or even higher physiological activity among this population.
      CONCLUSIONS: Findings suggested dysfunction of the hypothalamic-pituitary-adrenal
      axis and autonomic nervous system for some, but not all, parents of children with
      ASD. Further research is warranted.

PMID- 29652215
TI  - Stigma of Sickle Cell Disease: A Systematic Review.
AB  - The aim of this systematic review was to synthesize the literature regarding
      health-related stigma in adolescents and adults living with sickle cell disease
      (SCD). Four domains were identified from 27 studies: 1) social consequences of
      stigma, 2) the effect of stigma on psychological well-being, 3) the effect of
      stigma on physiological well-being, and 4) the impact of stigma on patient
      provider relationships and care-seeking behaviors. Current literature revealed
      that SCD stigma has detrimental consequences. Methodological issues as well as
      research and practice implications were identified. Future research should
      further examine the impact of health-related stigma on self-management of SCD.

PMID- 29652217
TI  - Forecasting air quality time series using deep learning.
AB  - : This paper presents one of the first applications of deep learning (DL)
      techniques to predict air pollution time series. Air quality management relies
      extensively on time series data captured at air monitoring stations as the basis
      of identifying population exposure to airborne pollutants and determining
      compliance with local ambient air standards. In this paper, 8 hr averaged surface
      ozone (O3) concentrations were predicted using deep learning consisting of a
      recurrent neural network (RNN) with long short-term memory (LSTM). Hourly air
      quality and meteorological data were used to train and forecast values up to 72
      hours with low error rates. The LSTM was able to forecast the duration of
      continuous O3 exceedances as well. Prior to training the network, the dataset was
      reviewed for missing data and outliers. Missing data were imputed using a novel
      technique that averaged gaps less than eight time steps with incremental steps
      based on first-order differences of neighboring time periods. Data were then used
      to train decision trees to evaluate input feature importance over different time
      prediction horizons. The number of features used to train the LSTM model was
      reduced from 25 features to 5 features, resulting in improved accuracy as
      measured by Mean Absolute Error (MAE). Parameter sensitivity analysis identified
      look-back nodes associated with the RNN proved to be a significant source of
      error if not aligned with the prediction horizon. Overall, MAE's less than 2 were
      calculated for predictions out to 72 hours. IMPLICATIONS: Novel deep learning
      techniques were used to train an 8-hour averaged ozone forecast model. Missing
      data and outliers within the captured data set were replaced using a new
      imputation method that generated calculated values closer to the expected value
      based on the time and season. Decision trees were used to identify input
      variables with the greatest importance. The methods presented in this paper allow
      air managers to forecast long range air pollution concentration while only
      monitoring key parameters and without transforming the data set in its entirety,
      thus allowing real time inputs and continuous prediction.

PMID- 29652218
TI  - Adsorptive conversion of nitrogen dioxide from etching vent gases over activated
      carbon.
AB  - : Some metal etching operations emit limited flow rates of waste gases with
      reddish-brown NO2 fume, which may cause visual and acidic-odor complaints, as
      well as negative health effects. In this study, tests were performed by passing
      caustic-treated waste gases vented from Al-etching operations through columns
      packed either with virgin or regenerated granular activated carbon (GAC) to test
      their adsorptive conversion performance of NO2 in the gases. The gases contained
      5-55 ppm NO2 and acetic and nitric acids of below 3 ppm. Exhausted carbon was
      regenerated by scrubbing it with caustic solution and water, and dried for
      further adsorption tests. Results indicate that with an (empty bed residence time
      (EBRT) of 0.15 sec for the gas through the GAC-packed space, around 60% of the
      influent NO2 of 54 ppm could be removed, and 47% of the removed NO2 was converted
      by and desorbed from the carbon as NO. GAC used in the present study could be
      regenerated at least twice to restore its capacity for NO2 adsorption. Within
      EBRTs of 0.076-0.18 sec, the adsorptive conversion capacity was linearly varied
      with EBRT. In practice, with an EBRT of 0.20 sec, a conversion capacity of 0.80
      kg NO2 (kg GAC)-1 with an influent NO2 of 40 ppm can be used as a basis for
      system design. IMPLICATIONS: Some metal etching operations emit waste gases with
      reddish-brown (yellow when diluted) NO2 fume which may cause visual and acidic
      odor complaints, as well as negative health effects. This study provides a simple
      process for the adsorptive conversion of NO2 in caustic-treated waste gases
      vented from metal-etching operations through a GAC column. With an EBRT of 0.20
      sec, a conversion capacity of 0.80 kg NO2 (kg GAC)-1 with an influent NO2 of 40
      ppm can be used as a basis for system design. Saturated GAC can be regenerated at
      least twice by simply scrubbing it with aqueous caustic solution.

PMID- 29652219
TI  - Organic compound emissions from a landfarm used for oil and gas solid waste
      disposal.
AB  - : Solid or sludgy hydrocarbon waste is a by-product of oil and gas exploration
      and production. One commonly used method of disposing of this waste is
      landfarming. Landfarming involves spreading hydrocarbon waste on soils, tilling
      it into the soil, and allowing it to biodegrade. We used a dynamic flux chamber
      to measure fluxes of methane, a suite of 54 nonmethane hydrocarbons, and light
      alcohols from an active and a remediated landfarm in eastern Utah. Fluxes from
      the remediated landfarm were not different from a polytetrafluoroethylene (PTFE)
      sheet or from undisturbed soils in the region. Fluxes of methane, total
      nonmethane hydrocarbons, and alcohols from the landfarm in active use were 1.41
      (0.37, 4.19) (mean and 95% confidence limits), 197.90 (114.72, 370.46), and 4.17
      (0.03, 15.89) mg m-2 hr-1, respectively. Hydrocarbon fluxes were dominated by
      alkanes, especially those with six or more carbons. A 2-ha landfarm with fluxes
      of the magnitude we observed in this study would emit 95.3 (54.3, 179.7) kg day-1
      of total hydrocarbons, including 11.2 (4.3, 33.9) kg day-1 of BTEX (benzene,
      toluene, ethylbenzene, and xylenes). IMPLICATIONS: Solid and sludgy hydrocarbon
      waste from the oil and gas industry is often disposed of by landfarming, in which
      wastes are tilled into soil and allowed to decompose. We show that a land farm in
      Utah emitted a variety of organic compounds into the atmosphere, including
      hazardous air pollutants and compounds that form ozone. We calculate that a 2-ha
      landfarm facility would emit 95.0 +/- 66.0 kg day-1 of total hydrocarbons,
      including 11.1 +/- 1.5 kg day-1 of BTEX (benzene, toluene, ethylbenzene, and
      xylenes).

PMID- 29652220
TI  - Meeting the Needs of Young Adolescents: ABBL Anti-Bullying Program During Middle
      School Transition.
AB  - This article introduces ABBL, the anti-bullying program for the transition to
      middle school, which was designed as a free, feasible, and easily applicable
      solution for teachers who, for any reason, cannot take advantage of comprehensive
      anti-bullying school-based programs. The ABBL, based on the identification of the
      causal risk factors and mechanisms that lead to bullying, aims to influence the
      peer group in such a way that students do not reward antisocial behaviors and
      are, instead, able to create supportive class atmospheres and strong networks of
      personal attachments. The evaluation of the program effectiveness showed that it
      reduced bullying in the classroom. Indications for wider implementations are
      presented together with the ready-to-use ABBL anti-bullying program (see
      http://blizej.org/abbl-antibullying-program/ ).

PMID- 29652221
TI  - When do the 'dark personalities' become less counterproductive? The moderating
      role of job control and social support.
AB  - INTRODUCTION: The objective of the study is to examine how job resources modify
      the relationship between the Dark Triad (DT) and counterproductive work behavior
      (CWB). Specifically the study examined: (a) the direct link between DT and CWB;
      (b) the moderation effects of two kinds of job resources (job control and social
      support); (c) the moderated moderation effect of the job resources (job control *
      social support) on the DT-CWB link. Moreover, the effect of social approval on
      CWB was controlled. METHOD: Data were collected among 659 white-collar and blue
      collar workers. The hypotheses were tested by means of the PROCESS method.
      RESULTS: As expected in the hypotheses, a high DT level was found to be directly
      related to high CWB, and job control moderated (intensified) the link. Social
      support did not moderate the DT-CWB link. The moderated moderation effect was
      supported. Social support increases the moderation effect of job control on the
      DT-CWB link. The lowest level of CWB is observed when job control was low and
      social support was high.

PMID- 29652222
TI  - Novel carbonized bone meal for defluoridation of groundwater: Batch and column
      study.
AB  - Low cost naturally available bone meal was carbonized and its fluoride adsorption
      capacity was explored. Carbonized bone meal (CBM) produced at 550 degrees C, 4 h
      carbonization time and a heating rate of 60 degrees C/min, showed fluoride
      adsorption capacity of 14 mg g-1. Adsorbent was characterized using scanning
      electron microscopy, X-ray diffraction, X-ray fluoroscence, thermogravimetric
      analysis and Fourier transform infrared spectroscopy to highlight its physical
      and chemical properties. Best fluoride uptake capacity was observed for 0.2 mm
      particle size, 7 g L-1 adsorbent concentration and at pH 6.5. Fluoride uptake was
      endothermic and chemisorption in nature. Effective diffusivity and mass transfer
      coefficient were obtained as 6 * 10-11 m2 s-1 and 9 * 10-5 m s-1 from shrinking
      core model. Sulphate and carbonate showed the highest interference effect on
      adsorption of fluoride by CBM. Maximum desorption was observed at basic pH (pH
      12). Fixed bed study was performed and effect of different parameters (bed
      height, inlet flow rate and initial concentration) was investigated. Efficiency
      of the adsorbent using real life fluoride contaminated groundwater solution was
      also observed.

PMID- 29652223
TI  - Preferences for the format of text messages containing results of online
      screening for sexually transmitted infections: a service evaluation.
AB  - We conducted an online survey to examine the preferences for receiving a text
      message with results of a test for sexually transmitted infections (STIs) as part
      of online self-sampling service at Solent NHS Trust. Findings showed that if all
      tests were negative, participants would prefer to receive one text message.
      However, in the event of a positive result, a large majority (86%) would prefer
      to receive a separate text with the name of the STI for which the test was
      positive. Similarly, three-quarters (74%) of participants would prefer to receive
      multiple texts indicating which test was inconclusive and required an additional
      sample. The results of this survey support a change of practice to sending
      multiple text messages with the results of online self-sampling that include the
      names of STIs.

PMID- 29652224
TI  - In vitro functional analysis of human cytochrome P450 2A13 genetic variants: P450
      2A13*2, *3, *4, and *10.
AB  - Humans possess three cytochrome P450 enzymes in the 2A subfamily (2A6, 2A7, and
      2A13). P450 2A13 is mainly expressed in the human trachea and lung, whereas P450
      2A6 is found in human liver. The P450 2A13 enzyme may be considered as the
      primary enzyme responsible for metabolic activation of many tobacco-specific
      carcinogens. Genetic variations significantly influence the toxicological
      consequences attributed to tobacco smoking. The aim of this study was to examine
      the in vitro functional activities of five P450 2A13 genetic variations (R257C,
      133_134insT, R101Q, I331T, and R257C/I331T) in P450 2A13*2, *3, *4, and *10
      alleles. Mutant clones were constructed and their recombinant enzymes were
      expressed in Escherichia coli. P450 2A13 mutants containing R257C, 133_134insT,
      I331T, and R257C/I331T displayed P450 holoenzyme spectra. The R101Q mutant was
      not apparently expressed. P450 2A13 enzymes displayed the typical type I binding
      spectra to coumarin and the calculated binding affinities of R257C, R257C/I331T,
      and 133_134insT mutants were decreased approximately three- to sevenfold. In
      catalytic analyses of purified mutant enzymes for coumarin and nicotine, the
      R257C and I331T mutants exhibited lower kcat values with catalytic efficiencies
      reduced up to approximately 20%. The double mutation of R257C/I331T induced
      increased Km values and diminished kcat values that resulted in >50% decrease in
      catalytic efficiencies. For 133_134insT mutant, catalytic activities were not
      markedly saturated but the measured rates at the highest concentrations were
      significantly lower than those of the wild-type or other mutant enzymes.
      Functional analysis of these variations in P450 2A13 allelic variants may help to
      understand the consequences of P450 2A13 polymorphism in bioactivation of many
      tobacco-derived carcinogens.

PMID- 29652225
TI  - Emission factors of atmospheric and climatic pollutants from crop residues
      burning.
AB  - : Biomass burning is a common agricultural practice, because it allows
      elimination of postharvesting residues; nevertheless, it involves an inefficient
      combustion process that generates atmospheric pollutants emission, which has
      implications on health and climate change. This work focuses on the estimation of
      emission factors (EFs) of PM2.5, PM10, organic carbon (OC), elemental carbon
      (EC), carbon monoxide (CO), carbon dioxide (CO2), and methane (CH4) of residues
      from burning alfalfa, barley, beans, cotton, maize, rice, sorghum, and wheat in
      Mexico. Chemical characteristics of the residues were determined to establish
      their relationship with EFs, as well as with the modified combustion efficiency
      (MCE). Essays were carried out in an open combustion chamber with isokinetic
      sampling, following modified EPA 201-A method. EFs did not present statistical
      differences among different varieties of the same crop, but were statistically
      different among different crops, showing that generic values of EFs for all the
      agricultural residues can introduce significant uncertainties when used for
      climatic and atmospheric pollutant inventories. EFs of PM2.5 ranged from 1.19 to
      11.30 g kg-1, and of PM10 from 1.77 to 21.56 g kg-1. EFs of EC correlated with
      lignin content, whereas EFs of OC correlated inversely with carbon content. EFs
      of EC and OC in PM2.5 ranged from 0.15 to 0.41 g kg-1 and from 0.33 to 5.29 g kg
      1, respectively, and in PM10, from 0.17 to 0.43 g kg-1 and from 0.54 to 11.06 g
      kg-1. CO2 represented the largest gaseous emissions volume with 1053.35-1850.82 g
      kg-1, whereas the lowest was CH4 with 1.61-5.59 g kg-1. CO ranged from 28.85 to
      155.71 g kg-1, correlating inversely with carbon content and MCE. EFs were used
      to calculate emissions from eight agricultural residues burning in the country
      during 2016, to know the potential mitigation of climatic and atmospheric
      pollutants, provided this practice was banned. IMPLICATIONS: The emission factors
      of particles, short-lived climatic pollutants, and atmospheric pollutants from
      the crop residues burning of eight agricultural wastes crops, determined in this
      study using a standardized method, provides better knowledge of the emissions of
      those species in Latin America and other developing countries, and can be used as
      inputs in air quality models and climatic studies. The EFs will allow the
      development of more accurate inventories of aerosols and gaseous pollutants,
      which will lead to the design of effective mitigation strategies and planning
      processes for sustainable agriculture.

PMID- 29652226
TI  - Purification characteristics of fine particulate matter treated by a self
      flushing wet electrostatic precipitator equipped with a flexible electrode.
AB  - : A self-flushing wet electrostatic precipitator was developed to investigate the
      removal performance for fine particles. Flexible material (polypropylene, 840A)
      and carbon steel in the form of a spiked band were adopted as the collection
      plate and discharge electrode, respectively. The particle concentration,
      morphology, and trace-element content were measured by electric low-pressure
      impactor, scanning electron microscope, and energy-dispersive x-ray spectroscopy,
      respectively, before and after the electrostatic precipitator. With increasing
      gas velocity, the collection efficiency of fine particles (up to 0.8 MUm in
      diameter) increased, while it decreased for particles with diameters larger than
      0.8 MUm. Increasing the dust inlet concentration increased the collection
      efficiency up to a point, from which it then declined gradually with further
      increases in the inlet concentration. The particulate matter after the wet
      electrostatic precipitator showed different degrees of agglomeration. The
      collection efficiency of trace elements within PM10 was less than that of the
      PM10 itself. Notably, the water consumption in the current setup was
      significantly lower than for other treatment processes of comparable collection
      efficiencies. IMPLICATIONS: Wet electrostatic precipitators, as fine filtration
      equipment, were generally applicable to coal-fired plants to reduce PM2.5
      emissions in China. However, high energy consumption and unstable operation, such
      as water usage and spray washing directly in the electric field, seriously
      restricted the further development. The utilization of self-flushing wet
      electrostatic precipitator can solve these problems to some extent.

PMID- 29652227
TI  - Former suicidal inpatients' experiences of treatment and care in psychiatric
      wards in Norway.
AB  - PURPOSE: The purpose of this study is to explore how former suicidal inpatients
      experienced treatment and care in psychiatric wards in Norway following the
      implementation of the National guidelines for prevention of suicide in mental
      health care. The focus of the analysis was on aspects of treatment and care with
      potential for improvement. METHOD: We interviewed five former inpatients and
      analysed the data by means of Interpretative Phenomenological Analysis. RESULTS:
      Experiencing a sense of companionship with the staff and receiving individualized
      treatment and care was important for the participants. This involved establishing
      trusting connections with mental health workers who treated them with respect,
      made them feel valued, and who recognized their suffering and needs. The formerly
      suicidal patients experienced being in a recovery process, which was promoted by
      the support of mental health workers. Although the participants reported mostly
      positive experiences, there were examples of insufficient care. Sometimes, they
      felt that their suffering and suicidality were not sufficiently recognized.
      CONCLUSION: Our study indicates that although there has been increased focus on
      suicidality in the mental health services, among other through clinical
      guidelines, some mental health workers still lack competence and should focus
      more fully on how to provide individualized care for suicidal inpatients.

PMID- 29652228
TI  - Prediction of clinical outcome in subacute subarachnoid hemorrhage using
      diffusion tensor imaging.
AB  - OBJECTIVE Clinical outcome in nontraumatic subarachnoid hemorrhage (SAH) is
      multifactorial and difficult to predict. Diffusion tensor imaging (DTI) findings
      are a prognostic marker in some diseases such as traumatic brain injury. The
      authors hypothesized that DTI parameters measured in the subacute phase of SAH
      can be associated with a poor clinical outcome. METHODS Diffusion tensor imaging
      was prospectively performed in 54 patients at 8-10 days after nontraumatic SAH.
      Logistic regression analysis was performed to evaluate the association of
      fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values with a
      poor clinical outcome (modified Rankin Scale score >= 3) at 3 months. RESULTS At
      8-10 days post-SAH, after adjusting for other variables associated with a poor
      outcome, an increased ADC at the frontal centrum semiovale was associated with a
      poor prognosis (OR estimate 1.29, 95% CI 1.04-1.60, p = 0.020). Moreover, an
      increase of 0.1 in the FA value at the corpus callosum at 8-10 days after SAH
      corresponded to 66% lower odds of having a poor outcome (p = 0.002). CONCLUSIONS
      Decreased FA and increased ADC values in specific brain regions were
      independently associated with a poor clinical outcome after SAH. This preliminary
      exploratory study supports a potential role for DTI in predicting the outcome of
      SAH.

PMID- 29652229
TI  - A useful diagnostic method to reduce the in-hospital time delay for mechanical
      thrombectomy: volume perfusion computed tomography with added vessel
      reconstruction.
AB  - OBJECTIVE Volume perfusion CT (VPCT) with added CT angiography (CTA)-like
      reconstruction from VPCT source data (VPCTA) can reveal multiple intracranial
      parameters. The authors examined the usefulness of VPCTA in terms of reducing the
      in-hospital time delay for mechanical thrombectomy. METHODS A total of 180
      patients who underwent mechanical thrombectomy at the authors' institution
      between January 2014 and March 2017 were divided into 2 groups: a CTA-based
      thrombectomy decision group (group 1: CTA) and a VPCTA-based decision group
      (group 2: VPCTA). Multiple time interval categories (from symptom onset to groin
      puncture, from hospital arrival to groin puncture, procedure time, from symptom
      onset to reperfusion, and from hospital arrival to reperfusion) were reviewed.
      All patients underwent clinical assessment with the National Institutes of Health
      Stroke Scale score and the modified Rankin Scale, and radiological results were
      evaluated by the Thrombolysis in Cerebral Infarction score. RESULTS In all of the
      time interval categories except for procedure time, the VPCTA group showed a
      significantly shorter in-hospital time delay during the prethrombectomy period
      than did the CTA group. The 3-month modified Rankin Scale score was significantly
      lower in the VPCTA group (2.8) compared with the CTA group (3.5) (p = 0.003) .
      However, there were no statistically significant differences between the 2 groups
      in the other clinical and radiological outcomes. CONCLUSIONS Compared with CTA,
      VPCTA significantly reduced the in-hospital time delay during the prethrombectomy
      period.

PMID- 29652230
TI  - Transposition of the lateral femoral cutaneous nerve.
AB  - OBJECTIVE Meralgia paresthetica causes pain, burning, and loss of sensation in
      the anterolateral thigh. Surgical treatment traditionally involves neurolysis or
      neurectomy of the lateral femoral cutaneous nerve (LFCN). After studying and
      publishing data on the anatomical feasibility of LFCN transposition, the author
      presents here the first case series of patients who underwent LFCN transposition.
      METHODS Nineteen patients with meralgia paresthetica were treated in the
      Department of Neurological Surgery at University of Wisconsin between 2011 and
      2016; 4 patients underwent simple decompression, 5 deep decompression, and 10
      medial transposition. Data were collected prospectively and analyzed
      retrospectively. No randomization was performed. The groups were compared in
      terms of pain scores (based on a numeric rating scale) and reoperation rates.
      RESULTS The numeric rating scale scores dropped significantly in the deep
      decompression (p = 0.148) and transposition (p < 0.0001) groups at both the 3-
      and 12-month follow-up. The reoperation rates were significantly lower in the
      deep-decompression and transposition groups (p = 0.0454) than in the medial
      transposition group. CONCLUSIONS Both deep decompression and transposition of the
      LFCN provide better results than simple decompression. Medial transposition
      confers the advantage of mobilizing the nerve away from the anterior superior
      iliac spine, giving it a straighter and more relaxed course in a softer muscle
      bed.

PMID- 29652231
TI  - Endoscopic endonasal transoculomotor triangle approach for adenomas invading the
      parapeduncular space: surgical anatomy, technical nuances, and case series.
AB  - OBJECTIVE Pituitary adenomas may extend into the parapeduncular space by invading
      through the roof of the cavernous sinus. Currently, a transcranial approach is
      the preferred choice, with or without the combination of an endonasal approach.
      In this paper the authors present a novel surgical approach that takes advantage
      of the natural corridor provided by the tumor to further open the oculomotor
      triangle and resect tumor extension into the parapeduncular space. METHODS Six
      injected specimens were used to demonstrate in detail the surgical anatomy
      related to the approach. Four cases in which the proposed approach was used were
      retrospectively reviewed. RESULTS From a technical perspective, the first step
      involves accessing the superior compartment of the cavernous sinus. The
      interclinoid ligament should be identified and the dura forming the oculomotor
      triangle exposed. The oculomotor dural opening may be then extended posteriorly
      toward the posterior petroclinoidal ligament and inferolaterally toward the
      anterior petroclinoidal ligament. The oculomotor nerve should then be identified;
      in this series it was displaced superomedially in all 4 cases. The posterior
      communicating artery should also be identified to avoid its injury. In all 4
      cases, the tumor invading the parapeduncular space was completely removed. There
      were no vascular injuries and only 1 patient had a partial oculomotor nerve palsy
      that completely resolved in 2 weeks. CONCLUSIONS The endoscopic endonasal
      transoculomotor approach is an original alternative for removal of tumor
      extension into the parapeduncular space in a single procedure. The surgical
      corridor is increased by opening the dura of the oculomotor triangle and by
      working below and lateral to the cisternal segment of the oculomotor nerve.

PMID- 29652232
TI  - Long-term tumor control following stereotactic radiosurgery for jugular
      paraganglioma using 3D volumetric segmentation.
AB  - OBJECTIVE The morbidity of gross-total resection of jugular paraganglioma (JP) is
      often unacceptable due to the potential for irreversible lower cranial
      neuropathy. Stereotactic radiosurgery (SRS) has been used at the authors'
      institution since 1990 for the treatment of JP and other benign intracranial
      tumors. Conventional means of assessing tumor progression using linear
      measurements or elliptical approximations are imprecise due to the irregular
      shape and insinuating growth pattern of JP. The objective of this study was to
      assess long-term tumor control in these patients by using slice-by-slice 3D
      volumetric segmentation of serial MRI data. METHODS Radiographic data and
      clinical records were reviewed retrospectively at a single, tertiary-care
      academic referral center for patients treated from 1990 to 2017. Volumetric
      analyses by integration of consecutive tumor cross-sectional areas (tumor
      segmentation) of serial MRI data were performed. Tumor progression was defined as
      volumetric growth of 15% or greater over the imaging interval. Primary outcomes
      analyzed included survival free of radiographic and clinical progression.
      Secondary outcomes included new or worsened cranial neuropathy. RESULTS A total
      of 85 patients were treated with Gamma Knife radiosurgery (GKRS) for JP at the
      authors' institution over the last 27 years. Sixty patients had pretreatment and
      serial posttreatment contrast-enhanced MRI follow-up suitable for volumetric
      analysis. A total of 214 MR images were analyzed to segment tumor images in a
      slice-by-slice fashion to calculate integral tumor volume. The median follow-up
      duration was 66 months (range 7-202 months). At 5 years the tumor progression
      free survival rate was 98%. Three tumors exhibited progression more than 10 years
      after GKRS. Estimated survival free of radiographic progression rates (95%
      confidence interval [CI]; n = number still at risk) at 5, 10, and 15 years
      following radiosurgery were 98% (95% CI 94%-100%; n = 34), 94% (95% CI 85%-100%;
      n = 16), and 74% (95% CI 56%-98%; n = 6), respectively. One patient with tumor
      progression required treatment intervention using external beam radiation
      therapy, constituting the only case of clinical progression. Two patients (3%)
      without preexisting lower cranial nerve dysfunction developed new ipsilateral
      vocal fold paralysis following radiosurgery. CONCLUSIONS SRS achieves excellent
      long-term tumor control for JP without a high risk for new or worsened cranial
      neuropathy when used in primary, combined modality, or recurrent settings. Long
      term follow-up is critical due to the potential for late radiographic progression
      (i.e., more than 10 years after SRS). As none of the patients with late
      progression have required salvage therapy, the clinical implications of this
      degree of tumor growth have yet to be determined.

PMID- 29652233
TI  - First-in-human evaluation of the Cleveland Multiport Catheter for convection
      enhanced delivery of topotecan in recurrent high-grade glioma: results of pilot
      trial 1.
AB  - OBJECTIVE Progress in management of high-grade gliomas (HGGs) has been hampered
      by poor access of potential therapeutics to the CNS. The Cleveland Multiport
      Catheter (CMC), which deploys 4 independent delivery microcatheters, was
      developed to be a reliable, high-volume delivery device for delivery of
      therapeutic agents to the brain and other solid organs. The authors undertook
      this first-in-human clinical trial effort to evaluate the delivery
      characteristics of the CMC in patients with HGGs. METHODS A series of pilot
      studies were launched after approval of a sponsor-investigator IND
      (investigational new drug) application to evaluate the delivery of topotecan and
      gadolinium-DTPA (Gd-DTPA) via the CMC in patients with recurrent HGG. The first
      pilot trial evaluated delivery into enhancing tumor and nonenhancing, tumor
      infiltrated brain. Two catheters were placed with the use of a conventional
      frameless stereotactic technique following a biopsy to confirm tumor recurrence,
      and drug infusion was performed both intraoperatively and postoperatively for a
      total of 96 hours with the same rate for all microcatheters. Delivery was
      assessed by intermittent MRI. RESULTS Three patients were enrolled in the first
      pilot study. MRI demonstrated delivery from all 6 catheters (24 microcatheters).
      The volume of distribution (Vd) of Gd-DTPA was heavily dependent upon CMC
      location (enhancing vs nonenhancing) with an approximately 10-fold difference in
      Vd observed (p = 0.005). There were no hemorrhages related to catheter placement
      or removal, and all 3 patients completed the protocol-defined treatment.
      CONCLUSIONS The CMC is capable of providing backflow-resistant drug delivery to
      the brain and brain tumors. The volume of distribution is heavily dependent upon
      the integrity of the blood-brain barrier. Assessment of delivery is essential for
      development of loco-regionally applied therapeutics in the CNS. Clinical trial
      registration no.: NCT02278510 (clinicaltrials.gov).

PMID- 29652235
TI  - Harvey Cushing's management of neurogenic thoracic outlet syndrome.
AB  - Harvey Cushing is widely regarded as one of the forefathers of neurosurgery, and
      is primarily associated with his work on intracranial pathology. However, he had
      a clinical and academic interest in peripheral nerve surgery. Through the
      courtesy of the Alan Mason Chesney Medical Archives, the surgical records of the
      Johns Hopkins Hospital from 1896 to 1912 were reviewed. The records of a single
      patient undergoing brachial plexus exploration and cervical rib resection were
      selected for detailed review. The operative report and accompanying illustrations
      demonstrate Cushing's interest in adding approaches to the pathology of the
      brachial plexus to his operative armamentarium.

PMID- 29652234
TI  - Computer-assisted planning for the insertion of stereoelectroencephalography
      electrodes for the investigation of drug-resistant focal epilepsy: an external
      validation study.
AB  - OBJECTIVE One-third of cases of focal epilepsy are drug refractory, and surgery
      might provide a cure. Seizure-free outcome after surgery depends on the correct
      identification and resection of the epileptogenic zone. In patients with no
      visible abnormality on MRI, or in cases in which presurgical evaluation yields
      discordant data, invasive stereoelectroencephalography (SEEG) recordings might be
      necessary. SEEG is a procedure in which multiple electrodes are placed
      stereotactically in key targets within the brain to record interictal and ictal
      electrophysiological activity. Correlating this activity with seizure semiology
      enables identification of the seizure-onset zone and key structures within the
      ictal network. The main risk related to electrode placement is hemorrhage, which
      occurs in 1% of patients who undergo the procedure. Planning safe electrode
      placement for SEEG requires meticulous adherence to the following: 1) maximize
      the distance from cerebral vasculature, 2) avoid crossing sulcal pial boundaries
      (sulci), 3) maximize gray matter sampling, 4) minimize electrode length, 5) drill
      at an angle orthogonal to the skull, and 6) avoid critical neurological
      structures. The authors provide a validation of surgical strategizing and
      planning with EpiNav, a multimodal platform that enables automated computer
      assisted planning (CAP) for electrode placement with user-defined regions of
      interest. METHODS Thirteen consecutive patients who underwent implantation of a
      total 116 electrodes over a 15-month period were studied retrospectively. Models
      of the cortex, gray matter, and sulci were generated from patient-specific whole
      brain parcellation, and vascular segmentation was performed on the basis of
      preoperative MR venography. Then, the multidisciplinary implantation strategy and
      precise trajectory planning were reconstructed using CAP and compared with the
      implemented manually determined plans. Paired results for safety metric
      comparisons were available for 104 electrodes. External validity of the
      suitability and safety of electrode entry points, trajectories, and target-point
      feasibility was sought from 5 independent, blinded experts from outside
      institutions. RESULTS CAP-generated electrode trajectories resulted in a
      statistically significant improvement in electrode length, drilling angle, gray
      matter-sampling ratio, minimum distance from segmented vasculature, and risk (p <
      0.05). The blinded external raters had various opinions of trajectory feasibility
      that were not statistically significant, and they considered a mean of 69.4% of
      manually determined trajectories and 62.2% of CAP-generated trajectories
      feasible; 19.4% of the CAP-generated electrode-placement plans were deemed
      feasible when the manually determined plans were not, whereas 26.5% of the
      manually determined electrode-placement plans were rated feasible when CAP
      determined plans were not (no significant difference). CONCLUSIONS CAP generates
      clinically feasible electrode-placement plans and results in statistically
      improved safety metrics. CAP is a useful tool for automating the placement of
      electrodes for SEEG; however, it requires the operating surgeon to review the
      results before implantation, because only 62% of electrode-placement plans were
      rated feasible, compared with 69% of the manually determined placement plans,
      mainly because of proximity of the electrodes to unsegmented vasculature.
      Improved vascular segmentation and sulcal modeling could lead to further
      improvements in the feasibility of CAP-generated trajectories.

PMID- 29652236
TI  - Validity of PROMIS in minimally invasive transforaminal lumbar interbody fusion:
      a preliminary evaluation.
AB  - OBJECTIVE Patient-reported outcomes are commonly used to evaluate treatment
      efficacy. Inefficiencies in standard measurement tools often prove to be a
      barrier to data collection. The Patient-Reported Outcomes Measurement Information
      System (PROMIS) was developed to overcome these limitations. This tool implements
      computer-adaptive testing, which enables the assessment of physical function in
      fewer questions than those required for "static" metrics. In spine surgery
      patients, moderate to strong correlations with Oswestry Disability Index (ODI)
      and the 36-Item Short Form Survey (SF-36) scores have been reported for PROMIS.
      However, to date, data regarding the efficacy of this tool for patients
      undergoing minimally invasive (MIS) transforaminal lumbar interbody fusion (TLIF)
      have been limited. METHODS A prospectively maintained registry of patients who
      have undergone primary 1- or 2-level MIS TLIF was reviewed retrospectively.
      Patients with incomplete PROMIS data were excluded. Changes in PROMIS physical
      function scores 6 weeks, 12 weeks, and 6 months after surgery were analyzed using
      paired t-tests. PROMIS scores were compared with traditional outcome measures,
      including SF-12 physical function, ODI, and visual analog scale (VAS) back and
      leg scores. Correlations were tested using the Pearson correlation coefficient,
      and the strength of association was interpreted as follows: small, 0.1 <= |r| <
      0.3; moderate, 0.3 <= |r| < 0.5; and large, |r| >= 0.5. Statistical significance
      was set at p < 0.05. RESULTS Seventy-four patients were included in this analysis
      after the exclusion of those without PROMIS scores. The mean preoperative PROMIS
      score was 35.92 +/- 6.98. Significant improvements were demonstrated in PROMIS
      scores 12 weeks (41.33, p < 0.001) and 6 months (43.58, p < 0.001) after surgery.
      PROMIS scores demonstrated a significant correlation with SF-12, ODI, and VAS leg
      scores (p < 0.05). Strong associations with PROMIS scores were observed for SF-12
      (r = 0.650 to 0.854), ODI (r = -0.525 to -0.831), and 6-month VAS back (r = 
      0.693) scores. CONCLUSIONS Physical function as measured by PROMIS improves
      significantly 12 weeks and 6 months after MIS TLIF. In addition, PROMIS scores
      have strong correlations with SF-12 and ODI scores. These results suggest that
      PROMIS scores can be used as a valid assessment of physical function in MIS TLIF
      patients. Further work is required to determine the full benefits of this measure
      in other spine populations.

PMID- 29652237
TI  - Failure of facet replacement system with metal-on-metal bearing surface and
      subsequent discovery of cobalt allergy: report of 2 cases.
AB  - The aim of this study was to report on 2 patients in whom metal-on-metal (MOM)
      facet replacements failed, with subsequent positive findings on allergy testing.
      Motion-preserving devices have been used with limited success when
      instrumentation is indicated in the mobile spine. MOM-bearing surfaces in
      orthopedics were developed to increase implant longevity, yet have been
      associated with numerous adverse outcomes, including local tissue reactions,
      pseudotumors, metallosis, and the need for revision surgery. Five patients with
      spinal stenosis and low-grade spondylolisthesis were randomized to undergo facet
      replacement surgery with the ACADIA facet replacement system at the authors'
      institution. Two patients experienced a return of neurological symptoms after a
      pain-free interval (< 2 years) with development of local tissue reaction and
      positive findings on allergy testing to cobalt, the metal in the MOM-bearing
      surface. Both patients underwent successful removal of the implant and revision
      to titanium posterior spinal fusion and interbody fusion without further
      complication. Motion-preserving devices have been designed and trialed for
      specific indications in the mobile spine. Given the adverse results from MOM
      devices in hip arthroplasty and now the early reports with MOM facet
      replacements, caution is warranted when moving forward with any MOM joint-bearing
      surface. Both patients presented here had an unusual tissue reaction locally and
      subsequent positive allergy testing results to cobalt. These 2 patients appear to
      have developed a delayed hypersensitivity reaction to the metal, likely from fine
      debris at the MOM interface.

PMID- 29652238
TI  - Challenge of handling a Charcot spinal arthropathy with a novel hybrid fibular
      autograft and expandable cage.
AB  - A 26-year-old man, who was paraplegic for 6 years due to a motor vehicle
      accident, presented to the authors' clinic following his incapacity to withstand
      a sitting posture, the frequent sensation of "clicks" in his back, and a
      complaint of back pain while in his wheelchair. On imaging, his dorsal spine
      showed a complete arthrodesis of the primarily fused vertebrae. However, distal
      to this segment, a Charcot spinal arthropathy with subluxation of T12-L1 was
      evident. Repair of this complex, uncommon, late complication of his paraplegia by
      the frequently used fusion techniques was shown to be inappropriate. A novel and
      elaborate surgical procedure is presented by which a complete fusion of the
      affected spine was secured. A left retrodiaphragmatic approach was used. Complete
      corpectomy of both the T-12 and L-1 vertebrae to the preserved endplates was
      performed. Most of the patient's fibula was resected and shaped for engrafting.
      The segment of the fibula was introduced into a mesh cage, before its
      intramedullary implantation into the T-12 and L-1 vertebrae. This 2-step
      procedure combined the hybrid use of a fibular autograft and an expandable mesh
      cage, incorporated one into the other, in an innovative intramedullary position.
      This intervention allowed the patient to resume his former condition as an
      extremely physically active patient with paraplegia. Nine years later, an
      asymptomatic early-stage Charcot spine was found at L5-S1, but no treatment is
      planned at this point.

PMID- 29652239
TI  - Ovotesticular Disorder of Sex Development (Ovotestis) in Simpson-Golabi-Behmel
      Syndrome: Expansion of the Clinical Spectrum.
AB  - Simpson-Golabi-Behmel syndrome type I (SGBS, OMIM312870), caused by defects of
      the GPC3 and GPC4 genes on chromosome Xq26, is an X-linked recessive
      macrosomia/multiple congenital anomaly disorder characterized by somatic
      overgrowth, coarse facial features, variable congenital anomalies, increased
      tumor risk, and mild-to-moderate neurodevelopmental anomalies. We report the
      postmortem findings in 3 second-trimester male siblings with SGBS who displayed
      ambiguous genitalia (in all 3) and gonadal dysgenesis (ovotestis) (in 1), thus
      expanding the SGBS spectrum to include these disorders of sex development.

PMID- 29652240
TI  - Umbilical Cord Coiling in High-risk Pregnancies: Associations With Determinants
      of Adverse Birth Outcomes and Iron Status.
AB  - Abnormal umbilical cord coiling has been associated with adverse neonatal
      outcomes, but the etiology of these findings remains poorly characterized. This
      study was undertaken to examine associations between cord coiling and maternal
      iron (Fe) status and to identify potential determinants of hypo- and hypercoiling
      in 2 higher risk obstetric groups: pregnant adolescents (<=18 years, n = 92) and
      adult women carrying twins (n = 49), triplets (n = 11), or quadruplets (n = 1).
      Umbilical cords were classified as hypo-, normo-, or hypercoiled using digital
      photographs to assess gross appearance. Hypocoiling and hypercoiling were
      observed in 44% (n = 86/195) and 13% (n = 26/195) of the combined study
      population. The prevalence of hypocoiling among women carrying multiples was over
      3-fold higher than the prevalence in singleton pregnancies based on the published
      data. Within the entire study population, hypocoiling was associated with a lower
      gestational age at birth when compared to normocoiling and hypercoiling (36.3 +/-
      3.6 weeks [n = 86] vs 37.8 +/- 2.7 [n = 83], P < .01, and 38.2 +/- 2.6 [n = 26],
      P < .01, respectively), whereas hypercoiling was associated with significantly
      lower serum ferritin when compared to normocoiling ( P < .01) and hypocoiling ( P
      < .001). In the multiples cohort only, hypercoiling was significantly associated
      with multiparity ( P < .01) and lower birth weight ( P < .05). Further studies
      are needed to identify the determinants and consequences of cord coiling.

PMID- 29652241
TI  - Bacterial Burden in Critically Injured Ventilated Patients Does Not Correlate
      with Progression to Pneumonia.
AB  - BACKGROUND: Ventilator-associated pneumonia (VAP) is common in critically injured
      patients. The pathogenesis of VAP is not completely understood. We hypothesized
      that mechanically ventilated trauma patients who develop pneumonia have a
      progressive increase in pathogen burden over the course of ventilation until a
      threshold for symptomatic pneumonia is reached, leading to clinical suspicion of
      VAP. METHODS: Critically injured adults ventilated for more than two successive
      days were enrolled. Patients underwent daily surveillance mini-bronchoscopic
      alveolar lavage (mBAL) while ventilated for 14 days or until extubation. Standard
      semi-quantitative cultures were performed, and the investigators were blinded to
      the results. Standard patient management was performed by the clinical team.
      Patients suspected of having VAP by the clinical team underwent bronchoscopic
      bronchoalveolar lavage (bBAL) and semi-quantitative culture, with VAP defined as
      clinical symptoms plus >104 colony-forming units (CFU) of bacteria. Standard
      statistical analysis for non-parametric data was performed. RESULTS: The 37
      patients enrolled were ventilated for a median of nine days. While ventilated, 23
      patients met the criteria for a clinical suspicion of VAP, of which two were too
      ill for bronchoscopy. Thus, 21 patients underwent bBALs because of a suspicion of
      VAP, and 13 (35%) were positive, with >104 CFU of one or more pathogens, and were
      treated for pneumonia. The bacterial burden on mBAL remained <104 CFU during
      ventilation for 32% of patients. None developed clinical symptoms of VAP. Two
      thirds (67%) had an mBAL bacterial burden of >104 CFU without clinical suspicion
      of VAP. Half (56%) of positive surveillance cultures were followed by clinical
      VAP, confirmed by bBAL, all of which had identical pathogens on mBAL and bBAL.
      Almost half (44%) of the patients with positive surveillance mBALs never
      developed clinical VAP. CONCLUSION: A significant percentage of critically
      injured, ventilated adults develop high bacterial burdens in the lungs early in
      their course, and many clear these bacteria without developing VAP. Further study
      is needed to identify the factors causing progression to VAP.

PMID- 29652242
TI  - Chiari decompression outcomes using ligamentum nuchae harvest and duraplasty in
      pediatric patients with Chiari malformation type I.
AB  - OBJECTIVE The choice of graft material for duraplasty in decompressions of Chiari
      malformations remains a matter of debate. The authors present a detailed
      technique for harvesting ligamenta nuchae, as well as the clinical and
      radiographic outcomes of this technique, in a case series. METHODS The authors
      conducted a retrospective study evaluating the outcomes of Chiari malformation
      type I decompression and duraplasty in children aged 0-18 years at a single
      institution from 2013 to 2016. They collected both intraoperative and
      postoperative variables and compared them qualitatively to published data.
      RESULTS During the study period, the authors performed 25 Chiari malformation
      decompressions with ligamentum nuchae graft duraplasties. Of the 25 patients, 10
      were females, and the mean age at surgery was 8.6 years (range 13 months to 18
      years). The median operative time was 163 minutes (IQR 152-187 minutes), with
      approximately 10 minutes needed by a resident surgeon to harvest the graft. The
      mean length of stay was 3 nights (range 2-6 nights), and the mean follow-up was
      12.6 months (range 0.5-43.5 months). One patient (4%) developed a CSF leak that
      was repaired using an oversewing patch. There were no postoperative
      pseudomeningoceles or infections. Of the 19 patients presenting with a syrinx,
      imaging showed improvement in 10 (53%) and 8 (42%) had stable syrinx size on
      imaging. Of 16 patients presenting with a symptomatic Chiari malformation, 14
      (87.5%) experienced resolution of symptoms and in 1 (4%) symptoms remained the
      same. One patient (4%) presented with worsening syrinx and symptoms 1.5 months
      after initial surgery and underwent repeat decompression. CONCLUSIONS The authors
      describe a series of clinical and imaging outcomes of patients who underwent
      Chiari malformation decompression and duraplasty with a harvested ligamentum
      nuchae. The rates of postoperative CSF leak are similar to established techniques
      of autologous and artificial grafts, with similarly successful outcomes. Further
      study will be needed with larger patient cohorts to more directly compare
      duraplasty graft outcomes.

PMID- 29652243
TI  - Dorsal rhizotomy for children with spastic diplegia of cerebral palsy origin:
      usefulness of intraoperative monitoring.
AB  - OBJECTIVE The utility of intraoperative neuromonitoring (ION), namely the study
      of muscle responses to radicular stimulation, remains controversial. The authors
      performed a prospective study combining ventral root (VR) stimulation for mapping
      anatomical levels and dorsal root (DR) stimulation as physiological testing of
      metameric excitability. The purpose was to evaluate to what extent the
      intraoperative data led to modifications in the initial decisions for surgical
      sectioning established by the pediatric multidisciplinary team (i.e.,
      preoperative chart), and thus estimate its practical usefulness. METHODS Thirteen
      children with spastic diplegia underwent the following surgical protocol. First,
      a bilateral intradural approach was made to the L2-S2 VRs and DRs at the exit
      from or entry to their respective dural sheaths, through multilevel interlaminar
      enlarged openings. Second, stimulation-just above the threshold-of the VR at 2 Hz
      to establish topography of radicular myotome distribution, and then of the DR at
      50 Hz as an excitability test of root circuitry, with independent identification
      of muscle responses by the physiotherapist and by electromyographic recordings.
      The study aimed to compare the final amounts of root sectioning-per radicular
      level, established after intraoperative neuromonitoring guidance-with those
      determined by the multidisciplinary team in the presurgical chart. RESULTS The
      use of ION resulted in differences in the final percentage of root sectioning for
      all root levels. The root levels corresponding to the upper lumbar segments were
      modestly excitable under DR stimulation, whereas progressively lower root levels
      displayed higher excitability. The difference between root levels was highly
      significant, as evaluated by electromyography (p = 0.00004) as well as by the
      physiotherapist (p = 0.00001). Modifications were decided in 11 of the 13
      patients (84%), and the mean absolute difference in the percentage of sectioning
      quantity per radicular level was 8.4% for L-2 (p = 0.004), 6.4% for L-3 (p =
      0.0004), 19.6% for L-4 (p = 0.00003), 16.5% for L-5 (p = 0.00006), and 3.2% for S
      1 roots (p = 0.016). Decreases were most frequently decided for roots L-2 and L
      3, whereas increases most frequently involved roots L-4 and L-5, with the largest
      changes in terms of percentage of sectioning. CONCLUSIONS The use of ION during
      dorsal rhizotomy led to modifications regarding which DRs to section and to what
      extent. This was especially true for L-4 and L-5 roots, which are known to be
      involved in antigravity and pelvic stability functions. In this series, ION
      contributed significantly to further adjust the patient-tailored dorsal rhizotomy
      procedure to the clinical presentation and the therapeutic goals of each patient.

PMID- 29652244
TI  - Deriving fuel-based emission factor thresholds to interpret heavy-duty vehicle
      roadside plume measurements.
AB  - : Remote sensing devices have been used for decades to measure gaseous emissions
      from individual vehicles at the roadside. Systems have also been developed that
      entrain diluted exhaust and can also measure particulate matter (PM) emissions.
      In 2015, the California Air Resources Board (CARB) reported that 8% of in-field
      diesel particulate filters (DPF) on heavy-duty (HD) vehicles were malfunctioning
      and emitted about 70% of total diesel PM emissions from the DPF-equipped fleet. A
      new high-emitter problem in the heavy-duty vehicle fleet had emerged. Roadside
      exhaust plume measurements reflect a snapshot of real-world operation, typically
      lasting several seconds. In order to relate roadside plume measurements to
      laboratory emission tests, we analyzed carbon dioxide (CO2), oxides of nitrogen
      (NOX), and PM emissions collected from four HD vehicles during several driving
      cycles on a chassis dynamometer. We examined the fuel-based emission factors
      corresponding to possible exceedances of emission standards as a function of
      vehicle power. Our analysis suggests that a typical HD vehicle will exceed the
      model year (MY) 2010 emission standards (of 0.2 g NOX/bhp-hr and 0.01 g PM/bhp
      hr) by three times when fuel-based emission factors are 9.3 g NOX/kg fuel and
      0.11 g PM/kg using the roadside plume measurement approach. Reported limits
      correspond to 99% confidence levels, which were calculated using the detection
      uncertainty of emissions analyzers, accuracy of vehicle power calculations, and
      actual emissions variability of fixed operational parameters. The PM threshold
      was determined for acceleration events between 0.47 and 1.4 mph/sec only, and the
      NOX threshold was derived from measurements where after-treatment temperature was
      above 200 degrees C. Anticipating a growing interest in real-world driving
      emissions, widespread implementation of roadside exhaust plume measurements as a
      compliment to in-use vehicle programs may benefit from expanding this analysis to
      a larger sample of in-use HD vehicles. IMPLICATIONS: Regulatory agencies, civil
      society, and the public at large have a growing interest in vehicle emission
      compliance in the real world. Leveraging roadside plume measurements to identify
      vehicles with malfunctioning emission control systems is emerging as a viable new
      and useful method to assess in-use performance. This work proposes fuel-based
      emission factor thresholds for PM and NOx that signify exceedances of emission
      standards on a work-specific basis by analyzing real-time emissions in the
      laboratory. These thresholds could be used to prescreen vehicles before roadside
      enforcement inspection or other inquiry, enhance and further develop emission
      inventories, and potentially develop new requirements for heavy-duty inspection
      and maintenance (I/M) programs, including but not limited to identifying vehicles
      for further testing.

PMID- 29652245
TI  - Prion Disease in Dromedary Camels, Algeria.
AB  - Prions cause fatal and transmissible neurodegenerative diseases, including
      Creutzfeldt-Jakob disease in humans, scrapie in small ruminants, and bovine
      spongiform encephalopathy (BSE). After the BSE epidemic, and the associated human
      infections, began in 1996 in the United Kingdom, general concerns have been
      raised about animal prions. We detected a prion disease in dromedary camels
      (Camelus dromedarius) in Algeria. Symptoms suggesting prion disease occurred in
      3.1% of dromedaries brought for slaughter to the Ouargla abattoir in 2015-2016.
      We confirmed diagnosis by detecting pathognomonic neurodegeneration and disease
      specific prion protein (PrPSc) in brain tissues from 3 symptomatic animals. Prion
      detection in lymphoid tissues is suggestive of the infectious nature of the
      disease. PrPSc biochemical characterization showed differences with BSE and
      scrapie. Our identification of this prion disease in a geographically widespread
      livestock species requires urgent enforcement of surveillance and assessment of
      the potential risks to human and animal health.

PMID- 29652246
TI  - Metformin in non-diabetic hyperglycaemia: the GLINT feasibility RCT.
AB  - BACKGROUND: The treatment of people with diabetes with metformin can reduce
      cardiovascular disease (CVD) and may reduce the risk of cancer. However, it is
      unknown whether or not metformin can reduce the risk of these outcomes in people
      with elevated blood glucose levels below the threshold for diabetes [i.e. non
      diabetic hyperglycaemia (NDH)]. OBJECTIVE: To assess the feasibility of the
      Glucose Lowering In Non-diabetic hyperglycaemia Trial (GLINT) and to estimate the
      key parameters to inform the design of the full trial. These parameters include
      the recruitment strategy, randomisation, electronic data capture, postal drug
      distribution, retention, study medication adherence, safety monitoring and remote
      collection of outcome data. DESIGN: A multicentre, individually randomised,
      double-blind, parallel-group, pragmatic, primary prevention trial. Participants
      were individually randomised on a 1 : 1 basis, blocked within each site. SETTING:
      General practices and clinical research facilities in Cambridgeshire, Norfolk and
      Leicestershire. PARTICIPANTS: Males and females aged >= 40 years with NDH who had
      a high risk of CVD. INTERVENTIONS: Prolonged-release metformin (500 mg)
      (Glucophage(r) SR, Merck KGaA, Bedfont Cross, Middlesex, UK) or the matched
      placebo, up to three tablets per day, distributed by post. MAIN OUTCOME MEASURES:
      Recruitment rates; adherence to study medication; laboratory results at baseline
      and 3 and 6 months; reliability and acceptability of study drug delivery;
      questionnaire return rates; and quality of life. RESULTS: We sent 5251
      invitations, with 511 individuals consenting to participate. Of these, 249 were
      eligible and were randomised between March and November 2015 (125 to the
      metformin group and 124 to the placebo group). Participants were followed up for
      0.99 years [standard deviation (SD) 0.30 years]. The use of electronic medical
      records to identify potentially eligible individuals in individual practices was
      resource intensive. Participants were generally elderly [mean age 70 years (SD
      6.7 years)], overweight [mean body mass index 30.1 kg/m2 (SD 4.5 kg/m2)] and male
      (88%), and the mean modelled 10-year CVD risk was 28.8% (SD 8.5%). Randomisation,
      postal delivery of the study drug and outcome assessment using registers/medical
      records were feasible and acceptable to participants. Most participants were able
      to take three tablets per day, but premature discontinuation of the study drug
      was common (~30% of participants by 6 months), although there were no differences
      between the groups. All randomised participants returned questionnaires at
      baseline and 67% of participants returned questionnaires by the end of the study.
      There was no between-group difference in Short Form questionnaire-8 items or
      EuroQol-5 Dimensions scores. Compared with placebo, metformin was associated with
      small improvements in the mean glycated haemoglobin level [-0.82 mmol/mol, 95%
      confidence interval (CI) -1.39 to -0.24 mmol/mol], mean estimated glomerular
      filtration rate (2.31 ml/minute/1.73 m2, 95% CI -0.2 to 4.81 ml/minute/1.73 m2)
      and mean low-density lipoprotein cholesterol level (-0.11 mmol/l, 95% CI -0.25 to
      0.02 mmol/l) and a reduction in mean plasma vitamin B12 level (-16.4 ng/l, 95% CI
      -32.9 to -0.01 ng/l). There were 35 serious adverse events (13 in the placebo
      group, 22 in the metformin group), with none deemed to be treatment related.
      LIMITATIONS: Changes to sponsorship reduced the study duration, the limited
      availability of information in medical records reduced recruitment efficiency and
      discontinuation of study medication exceeded forecasts. CONCLUSIONS: A large,
      pragmatic trial comparing the effects of prolonged-release metformin and placebo
      on the risk of CVD events is potentially feasible. However, changes to the study
      design and conduct are recommended to enable an efficient scaling up of the
      trial. Recommendations include changing the inclusion criteria to recruit people
      with pre-existing CVD to increase the recruitment and event rates, using large
      primary/secondary care databases to increase recruitment rates, conducting follow
      up remotely to improve efficiency and including a run-in period prior to
      randomisation to optimise trial adherence. TRIAL REGISTRATION: Current Controlled
      Trials ISRCTN34875079. FUNDING: The 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. 22, No. 18. See the NIHR
      Journals Library website for further project information. Merck KGaA provided
      metformin and matching placebo.

PMID- 29652247
TI  - Motor selection dynamics in FEF explain the reaction time variance of saccades to
      single targets.
AB  - In studies of voluntary movement, a most elemental quantity is the reaction time
      (RT) between the onset of a visual stimulus and a saccade toward it. However,
      this RT demonstrates extremely high variability which, in spite of extensive
      research, remains unexplained. It is well established that, when a visual target
      appears, oculomotor activity gradually builds up until a critical level is
      reached, at which point a saccade is triggered. Here, based on computational work
      and single-neuron recordings from monkey frontal eye field (FEF), we show that
      this rise-to-threshold process starts from a dynamic initial state that already
      contains other incipient, internally driven motor plans, which compete with the
      target-driven activity to varying degrees. The ensuing conflict resolution
      process, which manifests in subtle covariations between baseline activity, build
      up rate, and threshold, consists of fundamentally deterministic interactions, and
      explains the observed RT distributions while invoking only a small amount of
      intrinsic randomness.

PMID- 29652248
TI  - Microtubule assembly governed by tubulin allosteric gain in flexibility and
      lattice induced fit.
AB  - Microtubules (MTs) are key components of the cytoskeleton and play a central role
      in cell division and development. MT assembly is known to be associated with a
      structural change in [Formula: see text]-tubulin dimers from kinked to straight
      conformations. How GTP binding renders individual dimers polymerization
      competent, however, is still unclear. Here, we have characterized the
      conformational dynamics and energetics of unassembled tubulin using atomistic
      molecular dynamics and free energy calculations. Contrary to existing allosteric
      and lattice models, we find that GTP-tubulin favors a broad range of almost
      isoenergetic curvatures, whereas GDP-tubulin has a much lower bending
      flexibility. Moreover, irrespective of the bound nucleotide and curvature, two
      conformational states exist differing in location of the anchor point connecting
      the monomers that affects tubulin bending, with one state being strongly favored
      in solution. Our findings suggest a new combined model in which MTs incorporate
      and stabilize flexible GTP-dimers with a specific anchor point state.

PMID- 29652250
TI  - Design and modelling of an engineered bacteria-based, pressure-sensitive soil.
AB  - In this paper, we describe the first steps in the design of a synthetic
      biological system based on the use of genetically modified bacteria to detect
      elevated pressures in soils and respond by cementing soil particles. Such a
      system might, for example, enable a self- constructed foundation to form in
      response to load using engineered bacteria which could be seeded and grown in the
      soils. This process would reduce the need for large-scale excavations and may be
      the basis for a new generation of self-assembling and responsive bio-based
      materials. A prototype computational model is presented which integrates
      experimental data from a pressure sensitive gene within Escherichia coli bacteria
      with geotechnical models of soil loading and pore water pressure. The results
      from the integrated model are visualised by mapping expected gene expression
      values onto the soil volume. We also use our experimental data to design a two
      component system where one type of bacteria acts as a sensor and signals to
      another material synthesis bacteria. The simulation demonstrates the potential of
      computational models which integrate multiple scales from macro stresses in soils
      to the expression of individual genes to inform new types of design process. The
      work also illustrates the combination of in silico (silicon based computing)
      computation with in vivo (in the living) computation.

PMID- 29652249
TI  - Clathrin coat controls synaptic vesicle acidification by blocking vacuolar ATPase
      activity.
AB  - Newly-formed synaptic vesicles (SVs) are rapidly acidified by vacuolar adenosine
      triphosphatases (vATPases), generating a proton electrochemical gradient that
      drives neurotransmitter loading. Clathrin-mediated endocytosis is needed for the
      formation of new SVs, yet it is unclear when endocytosed vesicles acidify and
      refill at the synapse. Here, we isolated clathrin-coated vesicles (CCVs) from
      mouse brain to measure their acidification directly at the single vesicle level.
      We observed that the ATP-induced acidification of CCVs was strikingly reduced in
      comparison to SVs. Remarkably, when the coat was removed from CCVs, uncoated
      vesicles regained ATP-dependent acidification, demonstrating that CCVs contain
      the functional vATPase, yet its function is inhibited by the clathrin coat.
      Considering the known structures of the vATPase and clathrin coat, we propose a
      model in which the formation of the coat surrounds the vATPase and blocks its
      activity. Such inhibition is likely fundamental for the proper timing of SV
      refilling.

PMID- 29652251
TI  - Force and light tuning vertical tunneling current in the atomic layered MoS2.
AB  - In this work, the vertical electrical transport behavior of bilayer MoS2 under
      the coupling of force and light was explored by the use of conductive atomic
      force microscopy. We found that the current-voltage behavior across the tip-MoS2
      Pt junction is a tunneling current that can be well fitted by a Simmons
      approximation. The transport behavior is direct tunneling at low bias and Fowler
      Nordheim tunneling at high bias, and the transition voltage and tunnel barrier
      height are extracted. The effect of force and light on the effective band gap of
      the junction is investigated. Furthermore, the source-drain current drops
      surprisingly when we continually increase the force, and the dropping point is
      altered by the provided light. This mechanism is responsible for the tuning of
      tunneling barrier height and width by force and light. These results provide a
      new way to design devices that take advantage of ultrathin two-dimensional
      materials. Ultrashort channel length electronic components that possess tunneling
      current are important for establishing high-efficiency electronic and
      optoelectronic systems.

PMID- 29652252
TI  - On the application of the expected log-likelihood gain to decision making in
      molecular replacement.
AB  - Molecular-replacement phasing of macromolecular crystal structures is often fast,
      but if a molecular-replacement solution is not immediately obtained the
      crystallographer must judge whether to pursue molecular replacement or to attempt
      experimental phasing as the quickest path to structure solution. The introduction
      of the expected log-likelihood gain [eLLG; McCoy et al. (2017), Proc. Natl Acad.
      Sci. USA, 114, 3637-3641] has given the crystallographer a powerful new tool to
      aid in making this decision. The eLLG is the log-likelihood gain on intensity
      [LLGI; Read & McCoy (2016), Acta Cryst. D72, 375-387] expected from a correctly
      placed model. It is calculated as a sum over the reflections of a function
      dependent on the fraction of the scattering for which the model accounts, the
      estimated model coordinate error and the measurement errors in the data. It is
      shown how the eLLG may be used to answer the question 'can I solve my structure
      by molecular replacement?'. However, this is only the most obvious of the
      applications of the eLLG. It is also discussed how the eLLG may be used to
      determine the search order and minimal data requirements for obtaining a
      molecular-replacement solution using a given model, and for decision making in
      fragment-based molecular replacement, single-atom molecular replacement and
      likelihood-guided model pruning.

PMID- 29652253
TI  - Structural analysis of glycoproteins: building N-linked glycans with Coot.
AB  - Coot is a graphics application that is used to build or manipulate macromolecular
      models; its particular forte is manipulation of the model at the residue level.
      The model-building tools of Coot have been combined and extended to assist or
      automate the building of N-linked glycans. The model is built by the addition of
      monosaccharides, placed by variation of internal coordinates. The subsequent
      model is refined by real-space refinement, which is stabilized with modified and
      additional restraints. It is hoped that these enhanced building tools will help
      to reduce building errors of N-linked glycans and improve our knowledge of the
      structures of glycoproteins.

PMID- 29652254
TI  - Effects of protein-crystal hydration and temperature on side-chain conformational
      heterogeneity in monoclinic lysozyme crystals.
AB  - The modulation of main-chain and side-chain conformational heterogeneity and
      solvent structure in monoclinic lysozyme crystals by dehydration (related to
      water activity) and temperature is examined. Decreasing the relative humidity
      (from 99 to 11%) and decreasing the temperature both lead to contraction of the
      unit cell, to an increased area of crystal contacts and to remodeling of
      primarily contact and solvent-exposed residues. Both lead to the depopulation of
      some minor side-chain conformers and to the generation of new conformations. Side
      chain modifications and main-chain r.m.s.d.s associated with cooling from 298 to
      100 K depend on relative humidity and are minimized at 85% relative humidity
      (r.h.). Dehydration from 99 to 93% r.h. and cooling from 298 to 100 K result in a
      comparable number of remodeled residues, with dehydration-induced remodeling
      somewhat more likely to arise from contact interactions. When scaled to
      equivalent temperatures based on unit-cell contraction, the evolution of side
      chain order parameters with dehydration shows generally similar features to those
      observed on cooling to T = 100 K. These results illuminate the qualitative and
      quantitative similarities between structural perturbations induced by modest
      dehydration, which routinely occurs in samples prepared for 298 and 100 K data
      collection, and cryocooling. Differences between these perturbations in terms of
      energy landscapes and occupancies, and implications for variable-temperature
      crystallography between 180 and 298 K, are discussed. It is also noted that
      remodeling of a key lysozyme active-site residue by dehydration, which is
      associated with a radical decrease in the enzymatic activity of lysozyme powder,
      arises due to a steric clash with the residue of a symmetry mate.

PMID- 29652255
TI  - Gyre and gimble: a maximum-likelihood replacement for Patterson correlation
      refinement.
AB  - Descriptions are given of the maximum-likelihood gyre method implemented in
      Phaser for optimizing the orientation and relative position of rigid-body
      fragments of a model after the orientation of the model has been identified, but
      before the model has been positioned in the unit cell, and also the related
      gimble method for the refinement of rigid-body fragments of the model after
      positioning. Gyre refinement helps to lower the root-mean-square atomic
      displacements between model and target molecular-replacement solutions for the
      test case of antibody Fab(26-10) and improves structure solution with
      ARCIMBOLDO_SHREDDER.

PMID- 29652257
TI  - Structure and function of the type III pullulan hydrolase from Thermococcus
      kodakarensis.
AB  - Pullulan-hydrolysing enzymes, more commonly known as debranching enzymes for
      starch and other polysaccharides, are of great interest and have been widely used
      in the starch-saccharification industry. Type III pullulan hydrolase from
      Thermococcus kodakarensis (TK-PUL) possesses both pullulanase and alpha-amylase
      activities. Until now, only two enzymes in this class, which are capable of
      hydrolysing both alpha-1,4- and alpha-1,6-glycosidic bonds in pullulan to produce
      a mixture of maltose, panose and maltotriose, have been described. TK-PUL shows
      highest activity in the temperature range 95-100 degrees C and has a pH optimum
      in the range 3.5-4.2. Its unique ability to hydrolyse maltotriose into maltose
      and glucose has not been reported for other homologous enzymes. The crystal
      structure of TK-PUL has been determined at a resolution of 2.8 A and represents
      the first analysis of a type III pullulan hydrolyse. The structure reveals that
      the last part of the N-terminal domain and the C-terminal domain are
      significantly different from homologous structures. In addition, the loop regions
      at the active-site end of the central catalytic domain are quite different. The
      enzyme has a well defined calcium-binding site and possesses a rare vicinal
      disulfide bridge. The thermostability of TK-PUL and its homologues may be
      attributable to several factors, including the increased content of salt bridges,
      helical segments, Pro, Arg and Tyr residues and the decreased content of serine.

PMID- 29652256
TI  - Exploiting distant homologues for phasing through the generation of compact
      fragments, local fold refinement and partial solution combination.
AB  - Macromolecular structures can be solved by molecular replacement provided that
      suitable search models are available. Models from distant homologues may deviate
      too much from the target structure to succeed, notwithstanding an overall similar
      fold or even their featuring areas of very close geometry. Successful methods to
      make the most of such templates usually rely on the degree of conservation to
      select and improve search models. ARCIMBOLDO_SHREDDER uses fragments derived from
      distant homologues in a brute-force approach driven by the experimental data,
      instead of by sequence similarity. The new algorithms implemented in
      ARCIMBOLDO_SHREDDER are described in detail, illustrating its characteristic
      aspects in the solution of new and test structures. In an advance from the
      previously published algorithm, which was based on omitting or extracting
      contiguous polypeptide spans, model generation now uses three-dimensional volumes
      respecting structural units. The optimal fragment size is estimated from the
      expected log-likelihood gain (LLG) values computed assuming that a substructure
      can be found with a level of accuracy near that required for successful extension
      of the structure, typically below 0.6 A root-mean-square deviation (r.m.s.d.)
      from the target. Better sampling is attempted through model trimming or
      decomposition into rigid groups and optimization through Phaser's gyre
      refinement. Also, after model translation, packing filtering and refinement,
      models are either disassembled into predetermined rigid groups and refined
      (gimble refinement) or Phaser's LLG-guided pruning is used to trim the model of
      residues that are not contributing signal to the LLG at the target r.m.s.d.
      value. Phase combination among consistent partial solutions is performed in
      reciprocal space with ALIXE. Finally, density modification and main-chain
      autotracing in SHELXE serve to expand to the full structure and identify
      successful solutions. The performance on test data and the solution of new
      structures are described.

PMID- 29652258
TI  - The crystal structure of the lipoaminopeptaibol helioferin, an antibiotic peptide
      from Mycogone rosea.
AB  - The crystal structure of the natural nonapeptide antibiotic helioferin has been
      determined and refined to 0.9 A resolution. Helioferin consists of helioferin A
      and B, which contain 2-(2'-aminopropyl)aminoethanol (Apae) and 2-[(2'
      aminopropyl)methylamino]ethanol (Amae) at their respective alkanolamine termini.
      In addition, helioferin contains the unusual amino-acid residues alpha
      aminoisobutyric acid (Aib) and (2S,4S,6S)-2-amino-6-hydroxy-4-methyl-8
      oxodecanoic acid (Ahmod). The amino-terminus is capped with 2-methyl-n-1-octanoic
      acid (M8a). The peptide crystallizes with a 1:1 molar ratio of helioferin A and B
      in the monoclinic space group C2, with unit-cell parameters a = 34.711, b =
      10.886, c = 17.150 A, beta = 93.05 degrees . The peptide backbone folds in a
      regular right-handed alpha-helical conformation, with eight intramolecular
      hydrogen bonds, all but one forming 5->1 interactions. The two aliphatic chains
      of the fatty-acyl (M8a) and the second residue (Ahmod) extend out of the alpha
      helical structure in opposite directions and lead to a corkscrew-like shape of
      the peptide molecule. Halogen anions (Cl- and F-) have been co-crystallized with
      the peptide molecules, implying a positive charge at the aminoalcohol end of the
      peptide. In the tightly packed crystal the helices are linked head to tail via
      the anions by electrostatic, hydrogen-bond and van der Waals interactions,
      forming continuous helical rods. Two nonparallel rods (forming an angle of 118
      degrees ) interact directly via hydrogen bonds and via the anions, forming a
      double layer. Successive double layers are held together only via van der Waals
      contacts. The helical axes of successive double layers are also related by an
      angle of 118 degrees . The structure of helioferin reported here and the
      previously determined structure of the homologous leucinostatin A have a total
      straight length of about 21 A, indicating a different membrane-modifying
      bioactivity from that of long-chain, amphiphilic peptaibols.

PMID- 29652259
TI  - Structures of the Mycobacterium tuberculosis GlpX protein (class II fructose-1,6
      bisphosphatase): implications for the active oligomeric state, catalytic
      mechanism and citrate inhibition.
AB  - The crystal structures of native class II fructose-1,6-bisphosphatase (FBPaseII)
      from Mycobacterium tuberculosis at 2.6 A resolution and two active-site protein
      variants are presented. The variants were complexed with the reaction product
      fructose 6-phosphate (F6P). The Thr84Ala mutant is inactive, while the Thr84Ser
      mutant has a lower catalytic activity. The structures reveal the presence of a
      222 tetramer, similar to those described for fructose-1,6/sedoheptulose-1,7
      bisphosphatase from Synechocystis (strain 6803) as well as the equivalent enzyme
      from Thermosynechococcus elongatus. This homotetramer corresponds to a homologous
      oligomer that is present but not described in the crystal structure of FBPaseII
      from Escherichia coli and is probably conserved in all FBPaseIIs. The
      constellation of amino-acid residues in the active site of FBPaseII from M.
      tuberculosis (MtFBPaseII) is conserved and is analogous to that described
      previously for the E. coli enzyme. Moreover, the structure of the active site of
      the partially active (Thr84Ser) variant and the analysis of the kinetics are
      consistent with the previously proposed catalytic mechanism. The presence of
      metabolites in the crystallization medium (for example citrate and malonate) and
      in the corresponding crystal structures of MtFBPaseII, combined with their
      observed inhibitory effect, could suggest the existence of an uncharacterized
      inhibition of this class of enzymes besides the allosteric inhibition by
      adenosine monophosphate observed for the Synechocystis enzyme. The structural and
      functional insights derived from the structure of MtFBPaseII will provide
      critical information for the design of lead inhibitors, which will be used to
      validate this target for future chemical intervention.

PMID- 29652260
TI  - The crystal structure of the malic enzyme from Candidatus Phytoplasma reveals the
      minimal structural determinants for a malic enzyme.
AB  - Phytoplasmas are wall-less phytopathogenic bacteria that produce devastating
      effects in a wide variety of plants. Reductive evolution has shaped their genome,
      with the loss of many genes, limiting their metabolic capacities. Owing to the
      high concentration of C4 compounds in plants, and the presence of malic enzyme
      (ME) in all phytoplasma genomes so far sequenced, the oxidative decarboxylation
      of L-malate might represent an adaptation to generate energy. Aster yellows
      witches'-broom (Candidatus Phytoplasma) ME (AYWB-ME) is one of the smallest of
      all characterized MEs, yet retains full enzymatic activity. Here, the crystal
      structure of AYWB-ME is reported, revealing a unique fold that differs from those
      of 'canonical' MEs. AYWB-ME is organized as a dimeric species formed by
      intertwining of the N-terminal domains of the protomers. As a consequence of such
      structural differences, key catalytic residues such as Tyr36 are positioned in
      the active site of each protomer but are provided by the other protomer of the
      dimer. A Tyr36Ala mutation abolishes the catalytic activity, indicating the key
      importance of this residue in the catalytic process but not in the dimeric
      assembly. Phylogenetic analyses suggest that larger MEs (large-subunit or
      chimeric MEs) might have evolved from this type of smaller scaffold by gaining
      small sequence cassettes or an entire functional domain. The Candidatus
      Phytoplasma AYWB-ME structure showcases a novel minimal structure design
      comprising a fully functional active site, making this enzyme an attractive
      starting point for rational genetic design.

PMID- 29652261
TI  - Structural and functional roles of dynamically correlated residues in thymidylate
      kinase.
AB  - Thymidylate kinase is an important enzyme in DNA synthesis. It catalyzes the
      conversion of thymidine monophosphate to thymidine diphosphate, with ATP as the
      preferred phosphoryl donor, in the presence of Mg2+. In this study, the dynamics
      of the active site and the communication paths between the substrates, ATP and
      TMP, are reported for thymidylate kinase from Thermus thermophilus.
      Conformational changes upon ligand binding and the path for communication between
      the substrates and the protein are important in understanding the catalytic
      mechanism of the enzyme. High-resolution X-ray crystal structures of thymidylate
      kinase in apo and ligand-bound states were solved. This is the first report of
      structures of binary and ternary complexes of thymidylate kinase with its natural
      substrates ATP and ATP-TMP, respectively. Distinct conformations of the active
      site residues, the P-loop and the LID region observed in the apo and ligand-bound
      structures revealed that their concerted motion is required for the binding and
      proper positioning of the substrate TMP. Structural analyses provide an insight
      into the mode of substrate binding at the active site. The residues involved in
      communication between the substrates were identified through network analysis
      using molecular-dynamics simulations. The residues identified showed high
      sequence conservation across species. Biochemical analyses show that mutations of
      these residues either resulted in a loss of activity or affected the thermal
      stability of the protein. Further, molecular-dynamics analyses of mutants suggest
      that the proper positioning of TMP is important for catalysis. These data also
      provide an insight into the phosphoryl-transfer mechanism.

PMID- 29652262
TI  - The complex analysis of X-ray mesh scans for macromolecular crystallography.
AB  - In macromolecular crystallography, mesh (raster) scans are carried out either as
      part of X-ray-based crystal-centring routines or to identify positions on the
      sample holder from which diffraction images can be collected. Here, the methods
      used in MeshBest, software which automatically analyses diffraction images
      collected during a mesh scan and produces a two-dimensional crystal map showing
      estimates of the dimensions, centre positions and diffraction qualities of each
      crystal contained in the mesh area, are presented. Sample regions producing
      diffraction images resulting from the superposition of more than one crystal are
      also distinguished from regions with single-crystal diffraction. The
      applicability of the method is demonstrated using several cases.

PMID- 29652263
TI  - X-ray and UV radiation-damage-induced phasing using synchrotron serial
      crystallography.
AB  - Specific radiation damage can be used to determine phases de novo from
      macromolecular crystals. This method is known as radiation-damage-induced phasing
      (RIP). One limitation of the method is that the dose of individual data sets must
      be minimized, which in turn leads to data sets with low multiplicity. A solution
      to this problem is to use data from multiple crystals. However, the resulting
      signal can be degraded by a lack of isomorphism between crystals. Here, it is
      shown that serial synchrotron crystallography in combination with selective
      merging of data sets can be used to determine high-quality phases for insulin and
      thaumatin, and that the increased multiplicity can greatly enhance the success
      rate of the experiment.

PMID- 29652264
TI  - The oxygenating constituent of 3,6-diketocamphane monooxygenase from the CAM
      plasmid of Pseudomonas putida: the first crystal structure of a type II Baeyer
      Villiger monooxygenase. Corrigendum.
AB  - A statement is amended in the article by Isupov et al. [(2015). Acta Cryst. D71,
      2344-2353].

PMID- 29652265
TI  - Hydrogen bonds are a primary driving force for de novo protein folding.
      Corrigendum.
AB  - The paper by Lee et al. [(2017). Acta Cryst. D73, 955-969] is withdrawn.

PMID- 29652267
TI  - View point: Retraction is a pain but scientific misconduct is a crime!

PMID- 29652268
TI  - Dishonesty in medical research and publication and the remedial measures.

PMID- 29652269
TI  - Immediate extubation after cardiac surgery should be part of routine anesthesia
      practice for selected patients.

PMID- 29652270
TI  - Pulmonary hypertension and cardiac anesthesia: Anesthesiologist's perspective.
AB  - Perioperative management of pulmonary hypertension remains one of the most
      challenging scenarios during cardiac surgery. It is associated with high
      morbidity and mortality due to right ventricular failure, arrhythmias, myocardial
      ischemia, and intractable hypoxia. Therefore, this review article is intended
      toward the anesthetic considerations in the perioperative period, with particular
      emphasis on the selection of technique and choice of anesthesia with maintenance,
      anesthetic drugs, and the recent intraoperative recommendations for prevention
      and treatment of pulmonary hypertensive crisis.

PMID- 29652272
TI  - Comparison of immediate extubation versus ultrafast tracking strategy in the
      management of off-pump coronary artery bypass surgery.
AB  - Introduction: Ultrafast tracking of anesthesia (UFTA) is practiced routinely,
      whereas immediate on-table extubation after off-pump coronary artery bypass
      (OPCAB) grafting surgery has many concerns. The purpose of our study was to
      evaluate the safety and feasibility of immediate extubation (IE) versus UFTA.
      Methods: Sixty patients were enrolled who underwent OPCAB surgery. The two groups
      IE and UFTA had thirty patients each. Inclusion criteria were patients for OPCAB
      surgery including left main stenosis. Exclusion criteria were patients with
      Ejection Fraction(EF) <30%, with unstable hemodynamics, on intra-aortic balloon
      pump (IABP), with renal dysfunction, with associated valvular heart diseases, on
      inotropes, on temporary pacemaker, with intraoperative conversion to on-pump
      coronary artery bypass grafting (CABG), who are chronic smokers, and with chronic
      obstructive pulmonary disease. Statistical analysis was done with Minitab 15
      software. Descriptive statistics were summarized as mean, standard deviation, and
      percentage. Student's t-test was used to determine the significance of normally
      distributed parametric values. Z-test was used for proportion. Statistical
      significance was accepted at P < 0.05. Results: OT extubation was found to be
      safe as no patient had reintubation or respiratory insufficiency. None of the
      patients in either group had postoperative myocardial infarction, stroke, low
      cardiac output, mediastinitis, and renal failure. Hypothermia, blood transfusion,
      atrial fibrillation, and re-exploration did not occur. Intensive Care Unit length
      of stay was similar in the two groups. Discharge day is statistically significant
      (P = 0.001), with 5.66 days in the IE group and 6.36 days in the UFTA group. Time
      spent in the operating room at the end of surgery is statistically significant,
      with 14.03 min in UFTA group and 33.9 min in IE group. Conclusion: IE appears to
      be safe and effective in OPCAB patients without any major complications. It can
      be achieved after fulfilling traditional extubation criteria but is confined to
      highly selective group of patients.

PMID- 29652271
TI  - Prophylactic preoperative levosimendan for off-pump coronary artery bypass
      grafting in patients with left ventricular dysfunction: Single-centered
      randomized prospective study.
AB  - Background: Off-pump coronary artery bypass surgery (OPCAB) is often complicated
      by hemodynamic instability, especially in patients with prior left ventricular
      (LV) dysfunction and appropriate choice of inotrope plays a vital role in
      perioperative management of these patients. Aim and Objective: To study
      hemodynamic effects and immediate outcome of prophylactic infusion of
      levosimendan in patients with the LV dysfunction undergoing OPCAB surgery and
      whether this strategy helps in successful conduct of OPCAB surgery. Materials and
      Methods: After Institutional Ethics Committee approval, 60 patients posted for
      elective OPCAB surgery were randomly divided into two groups (n = 30 each).
      Patients with the LV ejection fraction <30% were included. Study group was
      started on injection levosimendan (@ 0.1 MUg/kg/min) in the previous night before
      surgery and continued for 24 h including intraoperative period. Hemodynamic
      monitoring included heart rate, invasive blood pressure, cardiac index (CI),
      pulmonary capillary wedge pressure (PCWP), pulse oximetry, and arterial blood
      gases with serum lactates at as T0 (baseline), T1 (15 min after obtuse marginal
      and/or PDA anastomoses), T2 (at end of surgery), T3 (6 h after surgery in
      Intensive Care Unit [ICU]), T4 (12 h after surgery), and T5 (24 h after surgery
      in ICU). Vasopressor was added to maintain mean arterial pressure >60 mmHg. Chi
      square/Fisher's exact/Mid P exact test and Student's t-tests were applied for
      categorical and continuous data. Results: CI was greater and PCWP reduced
      significantly in Group L during intraoperative and early postoperative period.
      Serum lactate concentration was lower in patients pretreated with levosimendan.
      Incidence of postoperative atrial fibrillation (POAF) (36.6 vs. 6.6%; P = 0.01),
      low cardiac output syndrome (LCOS) (30% vs. 6%; P = 0.02), and acute kidney
      injury (23.3% vs. 6.7%; P = 0.04) was less in Group L. Three patients (10%) in
      control group required conversion to cardiopulmonary bypass (CPB) as compared to
      none in the study group. There was no difference regarding ICU or hospital stay
      and mortality in both groups. Conclusion: Preoperative levosimendan helps in
      successful conduct of OPCAB and reduces the incidence of LCOS, POAF, conversion
      to CPB, and requirement of intra-aortic balloon pump.

PMID- 29652274
TI  - Milrinone: is bolus bad?

PMID- 29652273
TI  - Assessment of the effect of two regimens of milrinone infusion in pediatric
      patients undergoing fontan procedure: A randomized study.
AB  - Objective: The aim of the study was to compare the effect of two different
      regimens of milrinone on hemodynamics and oxygen saturation in pediatric patients
      undergoing Fontan procedure. Design: This was a randomized study. Setting:
      Cardiac centers. Patients: This study included 116 patients undergoing Fontan
      procedure. Material and Methods: Group E: Milrinone was started as infusion 0.5
      MUg/kg/min without a loading dose at the beginning of cardiopulmonary bypass
      (CPB) followed by infusion 0.5-0.75 MUg/kg/min in the pediatric cardiac surgical
      intensive care unit (PSICU). Group L: Milrinone was started as a loading dose 50
      MUg/kg over 10 min before weaning from CPB followed by infusion 0.5-0.75
      MUg/kg/min in the PSICU. Measurements: Heart rate, mean arterial blood pressure,
      central venous pressure, transpulmonary pressure, cardiac index, pharmacological
      support, lactate level, urine output, oxygen saturation, ICU, and hospital length
      of stay. Main Results: There were no changes in the heart rate and mean arterial
      blood pressure (P > 0.05). The increase in the postoperative central venous
      pressure, transpulmonary pressure and lactate level was lower in Group E than
      Group L (P < 0.05). The increase in the postoperative cardiac index, oxygen
      saturation, and urine output was higher in Group E than Group L (P < 0.05). The
      requirement for pharmacological support was lower in the Group E (P < 0.05). The
      ICU and hospital length of stay were shorter in the Group E than Group L (P <
      0.05). Conclusion: Early use of milrinone during Fontan procedure facilitated the
      weaning from CPB, decreased the elevation in the central venous pressure,
      transpulmonary gradient pressure, and the requirement for pharmacological
      support. Furthermore, it increased the cardiac index and arterial oxygen
      saturation.

PMID- 29652275
TI  - Dexmedetomidine versus ketofol sedation for outpatient diagnostic transesophageal
      echocardiography: A randomized controlled study.
AB  - Background: Moderate sedation is required for out-patient transesophageal
      echocardiography (TEE). Our objective was to compare the effect of Ketofol and
      dexmedetomidine for outpatient procedural sedation in diagnostic TEE with a
      hypothesis that Ketofol would be as effective as dexmedetomidine. Patients and.
      Methods: Fifty adult patients of age group 18-60 years with atrial septal defect,
      rheumatic valvular heart disease undergoing diagnostic TEE in the outpatient
      echocardiography laboratory were randomized into two groups, group D and group
      KF. GROUP D: Dexmedetomidine infusion -200 MUg in 20 ml normal saline. GROUP KF:
      Ketofol infusion: (ketamine: propofol, 1mg: 3 mg in 20 ml syringe). Loading dose
      of drug at 1ml/kg/hour IV till Ramsay sedation score (RSS) >= 3 achieved followed
      by maintenance infusion at 0.05 ml/kg/hour till end of procedure. Results: The
      primary outcome - time to achieve Ramsay sedation score >= 3 was significantly
      lesser with Ketofol as compared to Dexmedetomidine 260[69] seconds vs 460 [137],
      (p value<0.05). Conclusion: In out-patient setting, ketofol is favourable over
      dexmedetomidine for sedation regimen for diagnostic TEE as lesser time is taken
      to achieve optimal sedation with lesser hemodynamic perturbations, post procedure
      complications and better cardiologist satisfaction.

PMID- 29652276
TI  - Utility of thromboelastography versus routine coagulation tests for assessment of
      hypocoagulable state in patients undergoing cardiac bypass surgery.
AB  - Introduction: Peri-operative monitoring of coagulation is important to diagnose
      potential cause of hemorrhage, to manage coagulopathy and guide treatment with
      blood products in patients undergoing cardiac surgery with cardiopulmonary
      bypass. This study was done to evaluate usefulness of Thromboelastography (TEG)
      and routine coagulation tests (RCT) in assessing hemostatic changes and
      predicting postoperative bleeding in patients undergoing cardiac surgery with
      cardiopulmonary bypass. Methods: Fifty adult patients undergoing cardiac surgery
      with cardiopulmonary bypass were enrolled in this prospective study. Preoperative
      and post-operative samples were collected for routine coagulation tests and TEG.
      Regression analysis and test of significance using Pearson's correlation
      coefficient was performed to assess correlation between routine coagulation tests
      and corresponding TEG parameters .Regression analysis was done to study relation
      between blood loss at 24 hours and various coagulation parameters. Results: : The
      Routine coagulation test i.e. PT, INR, APTT showed no significant correlation
      with corresponding TEG parameters in pre-operative samples. However platelet
      count significantly correlated (p = 0.004) with MA values in postoperative
      samples. A significant correlation (p = 0.001) was seen between fibrinogen levels
      and alpha angles as well as with MA in both baseline preoperative and
      postoperative samples. TEG parameters R time and MA in postoperative samples were
      the only parameters that predicted bleeders with fair accuracy. Conclusion:
      Though the techniques of RCT and TEG are different, a few RCT e.g. platelet count
      and fibrinogen correlated with corresponding TEG parameters i.e. MA and Alpha
      angle. TEG parameters (R time and MA in postoperative samples) were able to
      predict blood loss better than RCT.

PMID- 29652277
TI  - Factors associated with delayed cardiac tamponade after cardiac surgery.
AB  - Context: Cardiac tamponade (CT) following cardiac surgery is a potentially fatal
      complication and the cause of surgical reintervention in 0.1%-6% of cases. There
      are two types of CT: acute, occurring within the first 48 h postoperatively, and
      subacute or delayed, which occurs more than 48 h postoperatively. The latter does
      not show specific clinical signs, which makes it more difficult to diagnose. The
      factors associated with acute CT (aCT) are related to coagulopathy or surgical
      bleeding, while the variables associated with subacute tamponade have not been
      well defined. Aims: The primary objective of this study was to identify the
      factors associated with the development of subacute CT (sCT). Settings and
      Design: This report describes a case (n = 80) and control (n = 160) study nested
      in a historic cohort made up of adult patients who underwent any type of urgent
      or elective cardiac surgery in a tertiary cardiovascular hospital. Methods: The
      occurrence of sCT was defined as the presence of a compatible clinical picture,
      pericardial effusion and confirmation of cardiac tamponade during the required
      emergency intervention at any point between 48 hours and 30 days after surgery.
      All factors potentially related to the development of sCT were taken into
      account. Statistical Analysis Used: For the adjusted analysis, a logistical
      regression was constructed with 55 variables, including pre-, intra-, and post
      operative data. Results: The mortality of patients with sCT was 11% versus 0% in
      the controls. Five variables were identified as independently and significantly
      associated with the outcome: pre- or post-operative anticoagulation,
      reintervention in the first 48 h, surgery other than coronary artery bypass
      graft, and red blood cell transfusion. Conclusions: Our study identified five
      variables associated with sCT and established that this complication has a high
      mortality rate. These findings may allow the implementation of standardized
      follow-up measures for patients identified as higher risk, leading to either
      early detection or prevention.

PMID- 29652279
TI  - A Commentary: effects on glargine insulin on glycemic control in patients with
      diabetes mellitus type II undergoing off-pump coronary artery bypass graft.

PMID- 29652278
TI  - Effects of glargine insulin on glycemic control in patients with diabetes
      mellitus type II undergoing off-pump coronary artery bypass graft.
AB  - Background: The prevalence of diabetes mellitus in patients requiring coronary
      artery bypass grafting (CABG) is noticeably high (20%-30%). These patients have
      inferior perioperative outcome, reduced long-term survival, and high risk of
      recurrent episodes of angina. To improve perioperative outcome surgical unit
      defined satisfactory glycemic control is desired during this period. Hence, the
      aim of our study is to compare the efficacy of glargine insulin combination with
      continuous human insulin infusion for perioperative glycemic control in patients
      with diabetes undergoing CABG. Materials and Methods: Fifty Patients, who were
      posted for off-pump CABG with diabetes mellitus type II, were randomized in two
      group, Group I normal saline + human insulin infusion during the perioperative
      period, Group II (glargine group): Glargine + human insulin infusion during
      perioperative period. Results: During surgery and in the postoperative period,
      random blood sugar and human insulin requirement are significantly higher in
      control group than glargine group. Other infection, step-up antibiotics,
      intensive care unit (ICU) stay, and hospital stay were significantly higher in
      control groups in postoperative period. Conclusion: Our study results suggest
      that glargine effectively manages blood glucose level with significantly greater
      control over postoperative morbidity.

PMID- 29652280
TI  - Relationship between maximum clot firmness in ROTEM(r) and postoperative bleeding
      after coronary artery bypass graft surgery in patients using clopidogrel.
AB  - Background: The aim of the present study was to investigate the relationship
      between maximum clot firmness (MCF) in rotational thromboelastometry (ROTEM(r))
      and postoperative bleeding in patients on clopidogrel after emergency coronary
      artery bypass graft surgery (CABG). Methods: This observational study recruited
      60 patients posted for emergency CABG following unsuccessful primary percutaneous
      coronary intervention (PCI) while on 600 mg of clopidogrel. The study population
      was divided into 2 groups on the basis of their MCF in the extrinsically
      activated thromboelastometric (EXTEM) component of the (preoperative) ROTEM(r)
      test: patients with MCF <50 mm (n = 16) and those with MCF >=50 mm (n = 44).
      Postoperative chest tube drainage amount, need for blood product transfusion,
      postoperative complications, and duration of mechanical ventilation after CABG
      were recorded. Results: No significant differences were observed between the two
      groups regarding duration of surgery, cardiopulmonary bypass, and aortic cross
      clamp time. Chest tube drainage at 6, 12, and 24 h after Intensive Care Unit
      admission were significantly higher in the patients with MCF below 50 mm. The
      need for blood product transfusion was higher in the group with MCF <50 mm. In
      patients who experienced postoperative bleeding of 1000 mL or more, the ROTEM(r)
      parameters of INTEM (Intrinsically activated thromboelastomery) alpha and MCF,
      EXTEM alpha and MCF, and HEPTEM (INTEM assay performed in the presence of
      heparinase) MCF (but not FIBTEM (Thromboelastometric assay for the fibrin part of
      the clot) values) were significantly lower than those with postoperative bleeding
      <1000 mL (P <= 0.05). Conclusions: When platelet aggregometry is not available,
      the ROTEM(r) test could be useful for the prediction of increased risk bleeding
      after emergency CABG in patients who have received a loading dose of clopidogrel.

PMID- 29652281
TI  - Indications and perioperative outcomes of extracorporeal life support in clermont
      ferrand.
AB  - Objectives: To report the epidemiological profile of the patients who underwent
      extracorporeal life support (ECLS) and then analyze the indications and outcomes
      of this procedure. Methods: It consisted of a retrospective and descriptive study
      based on the database from the department of cardiovascular surgery. Setting:
      University hospital clinic. Patients: One hundred and sixty-one patients have
      participated in the study. Included were all patients who presented with left
      sided heart or biventricular failure. Those who were suffering from either
      isolate respiratory failure or isolate right ventricle failure were excluded.
      Interventions: Participants underwent ECLS: central ECLS or peripheral ECLS.
      Results: : The mean age of the patients was 54 years; there were 73% of male
      patients and the mean duration of ECLS was 5.3 days. There were two types of
      ECLS: central (71%) and peripheral (29%). Indications for support were dominated
      by cardiogenic shock in 69%. Bleeding was the most frequent complication (23.5%).
      The overall in-hospital mortality of patients who underwent ECLS was 60%.
      Conclusion: The number of ECLS performed increases in proportion to mastery of
      surgical technique. There is a high rate of mortality and morbidity with ECLS.
      However, it remains a lifesaving therapy for many clinically urgent situations.

PMID- 29652282
TI  - Perioperative management of transcatheter, aortic and mitral, double valve-in
      valve implantation during pregnancy through left ventricular apical approach.
AB  - Pregnant women with stenotic degeneration of bioprosthetic cardiac valves may
      require another valve replacement procedure when their symptoms deteriorate with
      progression of pregnancy, but fetal mortality is higher with cardiac surgery done
      on cardiopulmonary bypass. Transcatheter valve-in-valve implantation may help to
      improve the fetal and maternal outcomes in these situations. Double valve-in
      valve implantation is rare and has not been reported in a pregnant patient. We
      report, for the first time, the case of a pregnant woman with stenotic
      bioprosthetic valves in the mitral and aortic positions, who underwent a
      successful concomitant, transcatheter, double valve-in-valve implantation through
      the left ventricular apical route during the second trimester of her precious
      pregnancy.

PMID- 29652283
TI  - Mitral valve repair in infective endocarditis during pregnancy.
AB  - Infective endocarditis (IE) during pregnancy and subsequent cardiac surgery are
      rare and associated with a high risk of mortality for the mother and fetus. It is
      difficult to determine the right time for cardiac intervention when IE is
      diagnosed early in pregnancy. A 33-year-old previously healthy woman in the 11th
      week of pregnancy was diagnosed with IE and underwent surgical intervention. The
      cardiopulmonary bypass settings and the anesthetic drugs were carefully chosen.
      Although she was in good health, while being discharged, the fetus did not
      survive. Anesthesiologists prioritizing the mother's survival should aim to
      improve fetal outcomes in such cases.

PMID- 29652284
TI  - Inverted left atrial appendage during minimally invasive mitral valve repair.
AB  - Inverted left atrial appendage (LAA) is a rare complication in cardiac surgery.
      The echocardiographic appearance often leads to misdiagnosis of thrombus or some
      other cardiac mass. Patients misdiagnosed in this way often undergo unnecessary
      anticoagulation or surgical treatment. Recently, minimally invasive mitral valve
      surgery (MIMVS) has become more widespread. However, as the incision for MIMVS
      through the right thoracotomy is very small, the inverted LAA is not within the
      surgical field of the cardiac surgeon. We present a case of inverted LAA during
      MIMVS and provide images from transesophageal echocardiography.

PMID- 29652285
TI  - Tricuspid stenosis: A rare and potential complication of ventricular septal
      occluder device.
AB  - Asymmetrical septal occluder device (ASOD) has made percutaneous closure of
      ventricular septal defect an easy and effective management option. Although there
      are reports of aortic and tricuspid valvular regurgitation after deployment of
      ASOD, only few cases of tricuspid stenosis (TS) has been reported so far in the
      literature. We report a case of malaligned ASOD that occurred after successful
      device closure resulting in TS along with mild tricuspid and aortic regurgitation
      requiring surgical retrieval. Transesophageal echocardiography played crucial
      role in detecting the cause of tricuspid valve dysfunction besides providing
      continuous monitoring during the procedure. We intend to emphasize the need of
      echocardiographic evaluation of the tricuspid valvular apparatus and aortic valve
      during and after the device deployment even after the successful device closure
      to prevent this rare complication.

PMID- 29652286
TI  - Anesthetic challenges of a patient with the communicating bulla coming for
      nonthoracic surgery.
AB  - Management of a patient with a giant bulla coming for a nonthoracic surgery is
      rare, and its anesthetic management is very challenging. It is imperative to
      isolate only the subsegmental bronchus, in which the bulla communicates to avoid
      respiratory morbidities such as pneumothorax, emphysema or atelectasis of the
      surrounding lung parenchyma, and postoperative respiratory failure. Herewith, we
      want to report the anesthetic challenges of a patient with giant bulla
      communicating into one of the subsegmental right upper lobe bronchus for
      splenectomy.

PMID- 29652287
TI  - A new right atrial mass following cardiopulmonary bypass mimicking a thrombus.
AB  - This report describes a patient with severe mitral stenosis who underwent mitral
      valve replacement. After completion of cardiopulmonary bypass, an unexpected
      finding of a right atrial mass was noticed on transesophageal echocardiography.
      The actual finding, possible differential diagnosis, and the management strategy
      are discussed.

PMID- 29652288
TI  - Absent superior vena cava in tetralogy of fallot.
AB  - Absent superior vena cava (SVC) is an asymptomatic congenital systemic venous
      anomaly which is rarely detected and compatible with normal life. Undiagnosed
      absent SVC may cause problems during cardiac catheterization or cardiac surgery.
      We present our surgical experience in a patient with tetralogy of Fallot who had
      undiagnosed absent SVC.

PMID- 29652289
TI  - Iatrogenic atrio-esophageal fistula following a video-assisted thoracoscopic maze
      procedure: Is esophageal instrumentation justified even when the diagnosis is
      equivocal?
AB  - A 74-year-old female underwent an uneventful bilateral thoracoscopic maze
      procedure for persistent atrial fibrillation with continuous transesophageal
      echocardiographic (TEE) guidance. She presented six weeks later with persistent
      fever and focal neurological signs. Computed tomography of the thorax revealed
      air in the posterior LA, raising suspicion for an abscess versus an
      atrioesophageal fistula (AEF). Before undergoing an exploratory median
      sternotomy, an esophagogastroduodenoscopy (EGD) was performed by the surgeon to
      check for any esophageal pathology. This however, resulted in sudden hemodynamic
      compromise that required intensive treatment with vasopressors and inotropes. In
      this case-report, we review the various intraoperative risk factors associated
      with the development of AEF during cardiac ablation procedures as well as the
      potential hazards of esophageal instrumentation with TEE, naso- or oro- gastric
      devices, and/or an EGD when an AEF is suspected.

PMID- 29652290
TI  - Absent right superior vena cava and persistent left superior vena cava in a
      patient with bicuspid aortic valve with aortic stenosis.
AB  - Persistent left superior vena cava (LSVC) with absent right SVC (RSVC) is a rare
      congenital anomaly. If undetected, the condition may pose difficulties in central
      venous catheter insertion, pacemaker electrode insertion, and cannulation during
      cardiopulmonary bypass. We describe a case of persistent LSVC with absent RSVC,
      who was diagnosed to have bicuspid aortic valve with aortic stenosis.

PMID- 29652291
TI  - Whole-lung lavage in a patient with pulmonary alveolar proteinosis.
AB  - Pulmonary alveolar proteinosis (PAP) is a rare syndrome in which
      phospholipoproteinaceous matter accumulates in the alveoli leading to compromised
      gas exchange. Whole-lung lavage is considered the gold standard for severe
      autoimmune PAP and offers favorable long-term outcomes. In this case report, we
      describe the perioperative management and procedural specifics of a patient
      undergoing WLL for PAP in which an anesthesiologist serves as the proceduralist
      and a separate anesthesiologist provides anesthesia care for the patient.

PMID- 29652292
TI  - Radio-opaque tricuspid aortic valve seen in X-Ray chest as mercedes-benz sign.
AB  - We are presenting a very interesting X-ray image of the calcific aortic valve in
      a septuagenarian male patient who underwent successful aortic valve replacement.

PMID- 29652293
TI  - Pediatric transesophageal echocardiography probe holder.

PMID- 29652294
TI  - Retraction: Annals of cardiac anesthesia: Beacon journey toward excellence: 2015
      2017.
AB  - [This retracts the article DOI: 10.4103/0971-9784.197801].

PMID- 29652295
TI  - Retraction: Is Endothelin Gene Polymorphism Associated with Postoperative Atrial
      Fibrillation in Patients Undergoing Coronary Artery Bypass Grafting?
AB  - [This retracts the article DOI: 10.4103/aca.ACA_264_16].

PMID- 29652296
TI  - Validation of the AAST EGS grade for Skin and Soft Tissue Infection.
AB  - INTRODUCTION: Skin and soft tissue infections (SSTI) present with variable
      severity. The American Association for the Surgery of Trauma (AAST) developed an
      emergency general surgery (EGS) grading system for several diseases. We aimed to
      determine whether the AAST EGS grade corresponds with key clinical outcomes.
      METHODS: Single institution retrospective review of patients (>=18 years)
      admitted with SSTI during 2012-2016 was performed. Patients with surgical site
      infections or <18 years were excluded. Laboratory Risk Indicator for Necrotizing
      Fasciitis (LRINEC) score and AAST EGS grade were assigned. The primary outcome
      was association of AAST EGS grade with complication development, duration of
      stay, and interventions. Secondary predictors of severity included tissue
      cultures, cross-sectional imaging, and duration of inpatient antibiotic therapy.
      Summary and univariate analyses were performed. RESULTS: A total of 223 patients
      were included (mean +/-SD age of 55.1+/-17.0 years, 55% male). The majority of
      patients received cross sectional imaging (169, 76%), or an operative procedure
      (155, 70%). SSTI tissue culture results included no growth (51, 24.5%),
      monomicrobial (83, 39.9%), and polymicrobial (74, 35.6%). Increased AAST EGS
      grade was associated with operative interventions, ICU utilization, complication
      severity (Clavien-Dindo index), duration of hospital stay, inpatient antibiotic
      therapy, mortality and hospital readmission. CONCLUSION: The AAST EGS grade for
      SSTI demonstrates the ability to correspond with several important outcomes.
      Prospective multi-institutional study is required to determine its broad
      generalizability in several populations. STUDY TYPE: Single institution
      retrospective review LEVEL OF EVIDENCE: IV.

PMID- 29652297
TI  - Carbapenemase producing Klebsiella pneumoniae in Peru: a case report and
      antimicrobial resistance discussion.
AB  - Carbapenemases are one of the major mechanisms of antimicrobial resistance,
      usually due to the indiscriminate use of antibiotics. The expansion of this
      mechanism of resistance at world level is imminent and control measures are
      limited. In the region of the Central Sierra of Peru - Huancayo, we report a case
      of carbapenemase-producing Klebsiella pneumoniae, with the purpose of discussing
      the problems related to this emerging mechanism of antibiotic resistance.

PMID- 29652298
TI  - [Cognitive processes in patients with different structure of anxiety disorders].
AB  - AIM: To study the relationship between cognitive functions and psychopathological
      disturbances in anxiety disorders. MATERIAL AND METHODS: WAIS, the modified
      Witkin's Embedded figures test, a symptom scale (Yu.A. Aleksandrovsky et al.
      1984) were administered to 111 patients, including 37 with generalized anxiety
      disorders (GAD, ICD-10 F41.1), 36 with anxiety-phobic disorders (AFD, ICD-10 F40)
      and 38 with anxiety-hypochondriac disorders (AHD, ICD-10 F45.2), and to 114
      healthy people. RESULTS AND CONCLUSION: A distinct trend towards an increase of
      cognitive impairment depending on an increase in the complicity of
      psychopathological picture was observed as follows: GAD - AFD - AHD. A decrease
      in visual-motor coordination and visual attention was found in patients with GAD.
      In AFD patients, besides disturbances characteristic of GAD, there was a decrease
      on the WAIS Vocabulary subtest. In AHD patients, there was a decrease in analytic
      and synthetic abilities. The heterogeneity of changes in cognitive processes and
      the structure of their correlations with psychopathological symptoms in anxiety
      disorders was revealed as follows: a decrease in some parameters of cognitive
      processes in anxiety disorders with mild structure, an increase in cognitive
      dysfunction and in a number of correlations in anxiety disorders with more
      complex psychopathological picture, higher scores on the WAIS Block design task.

PMID- 29652299
TI  - [Ataxia with oculomotor apraxia type 4 detected by next-generation sequencing].
AB  - Ataxias with oculomotor apraxia (AOA) belong to autosomal recessive ataxias.
      Their common feature is oculomotor apraxia: inability to coordinate eye movements
      not due to muscle weakness. Next-generation sequencing (NGS) gives unique
      opportunities of rare disorders diagnostics and discovering of new forms,
      including AOA. In 2015, AOA type 4 produced by PNKP mutations was delineated in a
      group of Portuguese patients. We diagnosed AOA4 in a 9-year-old boy from
      Byelorussian family. He presented with ataxia since 2 years and deterioration in
      8 years, oculomotor apraxia, dystonic hyperkinesia, dysarthria, polyneuropathy,
      borderline/mildly impaired intelligence, cerebellar atrophy on MRI and moderate
      hypercholesterolemia. Panel NGS detected two PNKP mutations: c.1123G>T
      (p.Gly375Trp) common in Portuguese patients, and novel
      c.1270_1283dupACAAACCCAGACGC (p.Ala429fs). This is one of a few world AOA4 cases
      and first non-Portuguese case with 'Portuguese' common mutation. The case
      illustrates NGS diagnostic value, particularly in rare heterogeneous disorders
      like AOA.

PMID- 29652300
TI  - [Predictors of remote outcomes of brain injury].
AB  - AIM: To determine predictors of remote outcomes of complex combat brain injury.
      MATERIAL AND METHODS: A survey of 145 combatants with long-term combat injury
      (from 1 to 10 years) was conducted. Responses were received from 30 people from
      18 regions of the Russian Federation. Data analysis included nonparametric
      correlation analysis using Spearman coefficient. RESULTS AND CONCLUSION:
      Significant correlations were between the remote functional outcome and the
      following predictors: the severity of injury at admission (r=0.527; p<0,01),
      leukocyte level at admission (r=0.594; p<0,01), presence and severity of pelvic
      disturbances (r=0.574; p<0,01), the duration of staying in intensive care
      (r=0.476; p<0,01), neurological deficit severity and scores on the Glasgow
      Outcome Scale (r=0.469; p<0,01). Character of remote outcome was associated with
      posttraumatic amnesia (r=0.491; p<0,05), concomitant injuries of abdominal cavity
      organs, kidney, bladder, time of starting peroral feeding (r=0.377; p<0,05), mean
      heart rhythm rate during the first 14 days of treatment, pneumonia (r=0.377;
      p<0,05) and episodes of psychomotor agitation (r=0.381; p<0,05) within a period
      of hospital treatment. These results need confirmation in a larger study.

PMID- 29652301
TI  - [The results of an open comparative retrospective trial of the course of multiple
      sclerosis during treatment with infibeta and other interferon-beta bioanalogues
      and glatiramer acetate].
AB  - AIM: To evaluate the efficacy and safety of the interferon beta-1b bioanalogue
      'infibeta' in the treatment of multiple sclerosis (MS) in comparison with other
      interferon beta bioanalogues and the generic drug glatiramer acetate. MATERIAL
      AND METHODS: The data of 500 patients with MS treated with different disease
      modifying drugs were analyzed. Patients of group 1 (n=95) received infibeta;
      group 2 (n=108) interferon beta-1b; group 3 (n=83) genfaxon-44; group 4 (n=109)
      sinnovex; group 5 (n=105) aksoglatiran FS. RESULTS: In all groups, there was a
      significant decrease in the AARR and an increase in the EDSS score (p<0,05) after
      12 and 24 months of treatment (p<0,05) with the best indicators in groups 1-3.
      After 12 months of treatment, the number of patients without signs of MRI
      activity was higher in groups 1-3 (48-61%) than in groups 4 and 5 (47, 43%,
      respectively) (p>0,05). After 24 months of treatment, the number of patients
      without signs of MRI activity decreased to 41-46% in groups 1-3, and more
      significantly in group 4 (27%). The percentage of NEDA-3 achieving patients did
      not significantly differ in the groups (23-32%) after 12 months of treatment.
      After 24 months of treatment the NEDA-3 declined more in group 4 (19%), least of
      all in groups 1 and 2 (27, 25%, respectively) (p>0,05). In most cases, the
      observed adverse events were mild or moderate. Flu-like syndrome was observed
      rarely in groups 1 and 4 (p<0,05). Injection reactions were observed most
      commonly in groups 3 and 5 (p<0,05). CONCLUSION: Infibeta, while retaining all
      the advantages of high-dose interferon beta, has the best tolerability profile,
      which makes it one of the optimal first line disease-modifying therapy for
      treatment of patients with MS.

PMID- 29652302
TI  - [Results of a multicenter study on the efficacy of cortexin in treatment of
      cognitive dysfunction in children].
AB  - AIM: To study the efficacy and tolerability of cortexin in the treatment of
      cognitive dysfunction in children. MATERIAL AND METHODS: The study included 635
      patients, aged 3-7 years. Patients were divided into 4 clinical groups: group 1
      (269 children with attention deficit hyperactivity disorder (ADHD)), group 2 (215
      children with speech delay), group 3 (82 patients with the consequences of a
      perinatal lesion of the central nervous system), group 4 (69 patients with
      asthenic/neurotic syndrome). Attention, visual memory and thinking were assessed
      before and after treatment. Standard treatment of cortexin, including 10
      intramuscular injections, was used. RESULTS AND CONCLUSION: The reliable effect
      of cortexin on cognitive impairment was shown. The best response to treatment was
      observed in patients with ADHD, aged 3-4 years, in particular on the tests
      measuring thinking. The tolerability of cortexin was good. It has been concluded
      that cortexin is an effective drug for treatment of children with ADHD, speech
      delay and consequences of a perinatal lesion of the central nervous system.

PMID- 29652303
TI  - [Respiratory hypercapnic-hypoxic training is an effective component of complex
      therapy of polyneuropathy in children with diabetes type 1].
AB  - AIM: To study the effectiveness of respiratory hypercapnic-hypoxic training in
      complex treatment of neuropathy due to diabetes type 1. MATERIAL AND METHODS:
      Fifty children, 31 girls and 19 boys, were examined. The inclusion criteria were
      the presence of polyneuropathy, verified on the basis of clinical data and
      electromyographic changes. The patients were divided into 2 groups: the main
      group (n=25, 15 girls and 10 boys, mean age 12.9+/-1.8 years (M+/-SD) and the
      comparison group (n=25, 16 girls and 9 boys, mean age 13.2+/-2.0 years). Patients
      of the main group, along with standard therapy received respiratory hypercapnic
      hypoxic training. RESULTS: The positive clinical and neurophysiological dynamics
      was noted in both groups, with more significant changes in children after
      respiratory training. CONCLUSION: Hypercapnic exercises significantly contribute
      to the pathogenetic therapy of diabetes mellitus and polyneuropathy in this
      disease, have a significant clinical effects reducing serum concentrations of
      fasting glucose and severity of neurological deficit scores on the NIS-LL,
      increasing the speed of conduction of excitation through the nerves, reducing the
      residual latency of EMG activity.

PMID- 29652304
TI  - [Approach for identifying of treatment option for pediatric patients in Guillain
      Barre syndrome considering results of pharmacoeconomic analysis].
AB  - AIM: A pharmacoeconomic analysis of direct costs on treatment with high dose
      intravenous immunoglobulins (IVIG) and plasmapheresis (PP) in children. MATERIAL
      AND METHODS: Literature data on the pathogenesis of Guillain-Barre syndrome (GBS)
      were analyzed. The results of pharmacoeconomic analysis of direct costs on
      treatment of GBS using IVIG and PP are presented. Risks for complications during
      treatment with IVIG and PP are calculated. RESULTS AND CONCLUSION: The
      pharmacoeconomic analysis demonstrates comparable costs of treatment with IVIG or
      PP in the Russian Federation. Nevertheless, a less number of complications,
      convenience in use and the good safety and tolerability profile make it more
      preferable to this group of patients. In a clinical case of a 7-year child
      described in the article, treatment with 10% IVIG - privigen in dose 2 g/kg
      during 5 days started in the 3rd week of disease showed a marked positive effect.

PMID- 29652305
TI  - [Efficiency of neuromultivit in complex therapy of patients with rheumatoid
      arthritis associated with diabetes mellitus].
AB  - AIM: To examine the dysregulation of the autonomic nervous system and
      manifestations of pain syndrome in patients with rheumatoid arthritis combined
      with diabetes mellitus and the possibility of their correction in patients who
      receive complex therapy including neurotropic vitamins (neuromultivitis).
      MATERIAL AND METHODS: One hundred and forty-six patients with rheumatoid disease
      were examined including 59 patients with diabetes mellitus. RESULTS AND
      CONCLUSION: When testing for the presence of neuropathic pain syndrome using the
      diagnostic questionnaire of neuropathic pain (DN4), a greater prevalence of these
      features was revealed, with a high correlation with the duration of rheumatoid
      arthritis (r=0,56) and duration of diabetes mellitus (r=0,82). A positive effect
      of combined therapy with neuromultivitis on the daily rhythm of arterial pressure
      with its normalization and correction of autonomic disorders was noted. There
      were a more pronounced decrease in the frequency and severity of parasympathetic
      and sympathetic failure, as well as an improvement in the adaptation of the
      peripheral vascular system to orthostatic changes. Improvement of quality of life
      is, to some extent, due to the more pronounced positive effect of combined
      therapy with neuromultivitis on such autonomic disorders as palpitations, heart
      rhythm disturbances, manifestations of lipotymic disorders and even panic
      attacks.

PMID- 29652306
TI  - [Assessment of clinical manifestations and treatment of post-stroke depression in
      young patients with ischemic stroke].
AB  - AIM: To consider clinical manifestations and treatment of post-stroke depression
      in young patients with carotid ischemic stroke. MATERIAL AND METHODS: Forty
      patients, 24 women and 16 men, aged from 18 to 45 years old, diagnosed with ICD
      10 post-stroke depression were examined. All patients underwent neurological
      examination, brain MRI and MR-angiography of cerebral vessels. The following
      psychometric tests were used: MMSE, Hamilton depression scale, CES-D depression
      scale, a questionnaire on nocturnal sleep assessment, and Epworth Sleepiness
      Scale. The Recovery Locus of Control Questionnaire was administered to evaluate
      motivation level for the post-stroke recovery. Patients were divided into two
      groups: group 1 (n=22) received basic treatment including milnacipran
      hydrochloride (ixel) in dose 1 capsule twice a day during 3 months, group 2
      received only basic treatment. Psychometric testing was performed 2 month after
      stroke before the treatment and 3 month after the end of treatment. RESULTS AND
      CONCLUSION: Patients demonstrated positive (melancholy, anxiety, intellectual and
      motor inhibition) and negative affectation (apathy, dysphoria) accompanied by
      somatic/autonomic disorders, in particular, sleep deficiency. A marked
      therapeutic effect of ixel was shown in group 1. The number of patients with
      depression decreased significantly after treatment compared to group 2. Sleep
      improvement and increased motivation levels for recovery were observed as well.

PMID- 29652307
TI  - [Therapy of asthenoneurotic syndrome in patients with focal muscular dystonia].
AB  - AIM: To analyze the prevalence and structure of asthenoneurotic disorders in
      patients with focal muscular dystonia and determine an effect of the anxiolytic
      adaptol (tetramethyltetraazabicyclooctandion) on asthenic syndrome in muscular
      dystonia. MATERIAL AND METHODS: Forty patients with focal muscular dystonia were
      examined. The severity of asthenic syndrome (MFI-20), anxiety (the Hospital scale
      of anxiety and depression) and depression (the Hamilton Depression Rating Scale)
      were evaluated. RESULTS AND CONCLUSION: Asthenic syndrome and anxiety disorder
      are independent non-motor manifestations of focal muscular dystonia. Adaptol has
      a positive effect, significantly reducing anxiety and asthenia in patients with
      focal muscular dystonia.

PMID- 29652308
TI  - [Clinical-psychopathological aspects of therapeutic effects of agomelatine
      (valdoxan) and its place in perfection of methods of therapy of postschizophrenic
      depressive disorders].
AB  - AIM: To determine a therapeutic effect of agomelatine (valdoxan) on post
      schizophrenic depression (PSD), taking into account its psychopathological
      structure. MATERIAL AND METHODS: A total of 33 patients of both sexes (average
      age was 32.1 yrs) with symptoms of post-schizophrenic depression (F20.4 according
      to ICD-10) were examined by using clinical and psychometric methods in the
      dynamics of shift-like schizophrenia. HAMD-17, PANSS and CGI-S scales were
      applied. All the patients were subdivided into groups: mild, moderate and severe
      depressions. Valdoxan was used at a dose of 25-50 mg/day for 28 days along with
      preceding antipsychotic therapy at maintenance doses. Evaluation of the efficacy
      of treatment was carried out according to percentage reduction of average total
      score (ATS) in dynamics. RESULTS: A significant effect of valdoxan, with 73.5% of
      PANSS score reduction and quicker response to treatment, was identified.
      Therapeutic effect of valdoxan on separate components of PSD was uneven. The
      decrease of depressive disorders per se assessed by HAMD-17 and PANSS G-subscale
      was equally high (78.4 and 78.2%, respectively). Therapeutic reduction of
      negative disorders according to PANSS N-subscale was the lowest, at the level of
      'good' effect (53.6%). In 27.3%, negative disorders were irreversible and were
      assessed as schizophrenic defect; in 72.7% of patients they were diagnosed as
      'secondary' negative symptoms in atypical depression. In the subgroups of mild,
      moderate, and severe depression, the reduction of negative disorders was 62.4;
      44.2 and 60.8%, respectively, and that of total PANSS score were 81.5; 66.1, and
      78.6%, i.e. there was no correlation between these variables. CONCLUSION:
      Agomelatin (valdoxan) is an effective medication for optimization of methods of
      PSD treatment, providing the therapeutic effect at the level of significant or
      complete reduction of symptoms. The quality (depth) and rate of formation of
      response in the dynamics of course treatment are determined not by the severity
      of depressive disorders in PSD structure, but by the ratio between negative
      (deficit) symptoms and 'secondary' symptoms, reflecting the degree of progression
      of the main disease.

PMID- 29652309
TI  - [Dynamics of clinical and biological indices of the asthenic symptom-complex
      during immunotropic therapy of patients with schizophrenia].
AB  - AIM: To identify clinical, psychopathological, and immunological features of the
      asthenic symptom-complex in patients with schizophrenia and to analyze the
      possibility of optimizing complex therapy of these conditions using the
      immunotropic drug bestim. MATERIAL AND METHODS: Forty-three male patients, aged
      20-55 years, were examined. Clinical examination of patients (PANSS, MFI-20) was
      performed before, and 5, 30 days after the end of treatment. The activity of
      inflammatory markers (leukocyte elastase (LE) and a1-proteinase inhibitor (a1
      PI)) was determined in blood serum. RESULTS: The affective-asthenic (32.5%) and
      asthenic-negative (67.5%) variants of the asthenic symptom-complex in
      schizophrenia characterized by different immune reactions (depending on LE
      activity) were revealed. Complex therapy with bestim contributed to a
      statistically significant reduction in the main clinical manifestations of
      endogenous asthenia in the majority of patients. More significant regression at a
      remote stage of the study was observed in the astheno-negative group of patients
      (p<0.001). CONCLUSION: LE and a1-PI reflect the clinical and biological features
      of the asthenic symptom-complex which develops within the endogenous process.
      Normal/reduced activity of LE accompanied by the increased activity of a1-PI is
      the best predictor of bestim efficacy in terms of reduction of asthenic symptoms.

PMID- 29652310
TI  - [Latent dysphoria: an instrument of screening and diagnosis (preliminary
      results)].
AB  - AIM: Latent dysphoria is a kind of emotional disorder. Its key features are
      floating feeling of dissatisfaction and irritability accompanied with suppression
      of expression of these emotions. The article is devoted to the development of a
      screening diagnostic tool (checklist) to screen and evaluate patients with this
      emotional problem. MATERIAL AND METHODS: Three hundred and ninety-four
      neurologists (outpatient segment) were surveyed to assess the prevalence of an
      emotional disorder that met criteria of latent dysphoria suggested by the
      authors. To develop a diagnostic tool, expert judgement method, with the
      involvement of 19 experts in different medical fields (psychiatry, psychology,
      gastroenterology, neurology), was used. RESULTS AND CONCLUSION: The final
      checklist contained the most typical signs of this disorder according to the
      opinion of the experts. The procedure of evaluation of these signs was developed.
      However, the results should be considered as preliminary and clinical psychiatric
      validation of the tool is needed.

PMID- 29652311
TI  - [Inflammatory factors and immunophenotypes in adjustment disorders].
AB  - AIM: To identify inflammatory and autoimmune markers (enzymatic activity of
      leukocyte elastase (LE), functional alpha1-proteinase inhibitor (alpha1-PI), the
      level of autoantibodies to neurospecific antigens S100b and myelin basic protein
      (MBP)) as well as phagocytic activity of blood neutrophils of patients with
      disorders of adaptation, to determine certain immunophenotypes and analyze their
      possible relationships with disease characteristics. MATERIAL AND METHODS: The
      study included 40 patients with adaptation disorders, mostly women. Diagnostic
      evaluation and clinical qualification of patients was carried out in accordance
      with ICD-10: 'Adjustment disorder' (F43.2). The control group consisted of 23
      individuals matched for age and sex with patients. The activity of LE and alpha1
      PI was determined by spectrophotometry, and the levels of autoantibodies to S100b
      and MBP by ELISA, phagocytic activity by the absorptive capacity of neutrophils
      of peripheral blood of melamine-formaldehyde latex particles. RESULTS: In the
      total group of patients with adaptation disorders, increased enzymatic activity
      of LE and functional alpha1-PI was shown compared to controls (p<0.001 and
      p<0.0001, respectively). There were no differences in the level of autoantibodies
      to neuroantigens, and changes in phagocytic index (PhN) compared with the
      control, however the tendency to reduction of phagocytic number (PhN) was
      observed. Patients were stratified by leading psychopathological symptoms
      (predominance of asthenic-depressive or anxious-depressive symptoms, polymorphic
      symptomatology) and by immunophenotype: (A) inflammatory markers - in the range
      of control values, (B) - the increase compared to the control activity of both LE
      and alpha1-PI, (C) preferential increase in the activity of alpha1-PI only. The
      frequency of these immunophenotypes was similar within each of the clinical
      subgroups. CONCLUSION: The results suggest the involvement of inflammation in the
      pathogenesis of adjustment disorders due to stress factors. Various immunological
      variants differed by proportion of inflammatory markers were not associated with
      clinical symptoms.

PMID- 29652312
TI  - [A study on the association of genes for pro-inflammatory cytokines and
      depression].
AB  - AIM: To study the association between proinflammatory cytokine genes and
      depression. MATERIAL AND METHODS: IL-1B S-511T and TNF-a G-308A gene
      polymorphisms were studied in patients diagnosed with depression and age and sex
      matched healthy controls. RESULTS AND CONCLUSION: The IL-1B S-511T and TNF-a G
      308A polymorphisms were associated with depression; CC genotype (r=0,001, OR=1.9
      CI 1,3-2,7) and GG genotype (r=0,001, OR=3,0 CI 1,8-4,9) were the risk factors.
      The results suggest that immune factors may play a role in the development of
      depression. The authors highlight the role of clinical polymorphism of depression
      that makes it difficult to form homogenous groups of patients and to select
      phenotypes for biological studies.

PMID- 29652313
TI  - [A short history of the united department of neurology named after academician
      S.N. Davidenkov (Dedicated to the 5 anniversary of I.I. Mechnikov North-Western
      State Medical University foundation)].

PMID- 29652314
TI  - [Cervical vertigo: a neurologist's point of view].
AB  - Cervical vertigo (CV) hasn't yet been recognized by many neurologists, as it has
      no specific clinical symptoms and reliable diagnostic criteria. However, over the
      past 150 years, there has been accumulated numerous experimental and clinical
      evidence to support the legitimacy of CV allocation as a separate nosology. This
      review presents data regarding the vertigo associated with neck pathology:
      possible evidence of CV existence and the description of its type as well. The
      principles of CV diagnosis and treatment are considered, an attempt to create a
      unified concept is proposed.

PMID- 29652315
TI  - [Music therapy procedures controlled by the brain potentials in treatment of
      functional disorders].
AB  - Twenty years ago, the Korsakov's Journal of Neurology and Psychiatry has
      published the article of Ya.I. Levin 'Brain music in the treatment of patients
      with insomnia'. This publication was the starting point for an innovative
      approach to preventing and correcting functional disorders of a person via
      musical or music-like stimuli that are controlled by the brain potentials of
      patient's. This approach called 'Music of the brain' is fully consistent with
      modern ideas about preventive neuroscience as a new field of scientific research
      at the intersection of neuroscience and preventive medicine. In this review, the
      authors analyze initial studies on the effects of music on the brain and discuss
      their limitations. To increase the effectiveness of the approach, a unique
      combination of musical therapy with the neurofeedback method, the technology of
      musical neurofeedback, has been developed. Results of the application of
      developed technology for treatment of human functional disorders are presented,
      and promising directions for further research are outlined.

PMID- 29652316
TI  - [Diaphragm relaxation surgery].
AB  - AIM: To develop examination algorithm and to determine the indications for
      various options for surgical treatment. MATERIAL AND METHODS: It is presented
      analysis of surgical treatment of 25 patients with unilateral diaphragm
      relaxation for the period from 1963 to 2016. There were 15 men and 10 women aged
      from 39 to 65 years. Diagnosis included predominantly radiological methods. All
      patients were operated openly through thoracotomy. Procedure consisted of
      creation of new diaphragmatic cupola at the usual level with two flaps of
      diaphragm and prosthesis between them. In 12 (48%) patients who were operated
      before 1990 xenopericardial patch was used. Further, synthetic materials (Teflon,
      polypropylene) were preferred. RESULTS: Postoperative morbidity and mortality was
      20% (n=6) and 4% (n=1) respectively. Long-term results were followed-up within
      terms from 8 months to 12 years. Recurrent relaxation was absent. Most of
      patients had improved dyspnea, increased vital capacity and FEV1 in long-term
      period. Certain and general values of SF-36 life quality questionnaire were high
      in long-term postoperative period and similar to those in general population.

PMID- 29652317
TI  - [Video-assisted thoracoscopic thymectomy in myasthenia gravis. New approach].
AB  - AIM: To present possibility and technical aspects of anesthetic management during
      video-assisted thoracoscopic thymectomy in patients with myasthenia gravis.
      MATERIAL AND METHODS: The article describes the proposed modified anesthetic
      method that is suitable for video-assisted thoracoscopic thymectomy in patients
      with myasthenia gravis. Nine patients with myasthenia underwent VATS-thymectomy.
      Anesthesia was performed with artificial airway and auxiliary ventilation without
      muscle relaxants administration.

PMID- 29652318
TI  - [Pulmonary metastases: classification and the need for staging?]
AB  - AIM: To analyze pulmonary metastases classifications which are used in Russian
      and foreign literature at present time. MATERIAL AND METHODS: It is proposed the
      variant of pulmonary metastases staging depending on quantitative and regional
      prevalence of the process. RESULTS: The development of pulmonary metastases
      classification is advisable to determine homogeneous subgroups of patients with
      metastatic lesion for prospective randomized trials in order to obtain objective
      results about the results of surgical or other local treatment of patients with
      intrapulmonary metastases.

PMID- 29652319
TI  - [Modern approaches to the diagnosis of precancerous pathology and early lung
      cancer].
AB  - AIM: To assess the possibilities of modern diagnostic techniques to diagnose
      precancerous pathology and early central lung cancer. MATERIAL AND METHODS:
      Analysis of Russian and foreign publications for precancerous pathology and early
      lung cancer, results and comparison of various diagnostic techniques. RESULTS:
      Central lung cancer has a stepwise development with transformation of normal
      bronchial epithelium to hyperplastic followed by focal metaplasia, dysplasia,
      cancer in situ (CIS) and microinvasive cancer. Fluorography, chest X-ray,
      computed tomography, magnetic resonance imaging and sputum cytology examination
      are used to diagnose lung cancer. However, endoscopy plays a leading role in
      diagnosis of early central lung cancer which rapidly and effectively detects
      changes of tracheobronchial tree mucosa at the initial stages of carcinogenesis
      thanks to the use of modern techniques (spectral, autofluorescent and ZOOM -
      endoscopy).

PMID- 29652320
TI  - [Bronchial fistula management. Is the exit found?]
AB  - AIM: To present treatment of bronchial fistulas by using of occluders. MATERIAL
      AND METHODS: For the period from March 2015 to October 2016 Atrial Septal Defect
      (ASD) occluders have been used for bronchial fistulas occlusion (Lepu Medical
      Technology Co., Ltd.; Lifetech Scientific Co., Ltd.). These are devices designed
      to close ventricular and atrial septal defects. The procedure was performed in 8
      patients with main bronchus fistula occurred after pulmonectomy for tuberculosis
      in 5 patients and lung cancer in 3 patients. Fistulas' dimensions were 6-26 mm.
      The procedure was performed with double visualization from pleural cavity
      (through the thoracostomy and port-assisted approach) and from bronchial lumen.
      RESULTS: Seven out of 8 patients are currently alive (1 patient died from
      advanced tuberculosis of single lung). Occlusion is adequate in 6 patients, air
      drainage around around the occluder is noted in 1 patient. In 1 patient
      esophageal-pleural fistula occurred besides bronchial fistula. There was
      significant 2-3-fold decrease of residual pleural cavities volume and output
      volume. Patients feel satisfactory.

PMID- 29652321
TI  - [Cytokines in surgery for pulmonary tuberculosis].
AB  - AIM: To evaluate the effect of various methods of thoracoplasty on local
      production of cytokines in patients with pulmonary tuberculosis. MATERIAL AND
      METHODS: The main group consisted of patients after traditional thoracoplasty.
      Thoracoplasty was compared with endoprosthesis of polypropylene mesh 'Surgipro -
      SPMM-149'. TNF-alpha and IL-10 cytokines in exudate from surgical area were
      measured by using of solid-phase enzyme immunoassay (OOO 'Vector-Best', Russia).
      RESULTS: It was revealed that local production of pro- and anti-inflammatory
      cytokines is more pronounced after thoracoplasty with polypropylene mesh
      'Surgipro - SPMM-149'. Local cytokine balance changes towards inflammation were
      more pronounced after thoracoplasty with mesh implant and did not depend on the
      degree of drug sensitivity.

PMID- 29652322
TI  - [Treatment of primary choriocarcinoma of lung].

PMID- 29652323
TI  - [Minimally invasive surgery for benign esophageal mesenchymal tumors].

PMID- 29652324
TI  - [Dangerous complication of vacuum-therapy for post-sternotomy wound infectious
      complications].

PMID- 29652325
TI  - Twisting partially coherent light.
AB  - Twisted Gaussian Schell-model beams were introduced 25 years ago as a celebrated
      example of a "genuinely two-dimensional" partially coherent wavefield. Today, a
      definite answer about the effect that a twist phase should produce on an
      arbitrary cross-spectral density has not yet been reached. In the present Letter,
      the necessary and sufficient condition for a typical Schell-model partially
      coherent CSD endowed with axial symmetry to be successfully mapped onto a
      bonafide twisted CSD is addressed. In particular, it is proved that any shift
      invariant degree of coherence of the form MU(|r1-r2|) is "twistable" if and only
      if the zeroth-order Hankel transform of the radial function MU(r)exp(ur2/2) (with
      u being the twist strength) turns out to be a well-defined, non-negative
      function.

PMID- 29652326
TI  - Low-power broadband all-optical switching via intermodal cross-phase modulation
      in integrated optical waveguides.
AB  - We demonstrate the potential of all-optical switches in integrated waveguides
      based on intermodal cross-phase modulation between transverse modes. For this
      purpose, the differential phase between two transverse modes of a probe beam was
      altered by cross-phase modulation with a control beam propagating only in the
      fundamental mode. A switching behavior was accomplished by spatially filtering
      the resulting multimode interference of the probe modes, which changed depending
      on the control beam power. All-optical switching with a contrast of 82% at 1280
      nm over a frequency range of 4.4 THz at 1.6 nJ was achieved, representing an
      improvement of the product of necessary power and waveguide length by a factor of
      nearly 2000 compared to similar experiments in graded-index fibers. Additionally,
      we show that the center wavelength of the switch can be tailored by changing the
      cross-sectional geometry of the waveguide or the involved probe modes.

PMID- 29652327
TI  - Dual-reference digital holographic interferometry for analyzing high-density
      gradients in fluid mechanics.
AB  - This Letter proposes a dual-reference digital holographic interferometer for
      analyzing the high refractive index encountered in transonic and supersonic
      flows. For that, a Wollaston prism is inserted in the reference arm in order to
      simultaneously generate two orthogonally polarized reference waves. As a
      consequence, recorded interferograms contain two crossed and perpendicular
      interference patterns that give two orders fully separated in the Fourier
      spectrum. It is then possible to analyze a transparent object regardless of the
      orientation of the refractive index gradient using the two phase maps
      reconstructed with each of the two first interference orders. Fusion of the phase
      maps yields a single phase map in which the phase singularities are removed.
      Experimental results demonstrate the suitability of the proposed approach for
      analyzing shock waves in the unsteady wake flow around a circular cylinder at
      Mach 0.75.

PMID- 29652328
TI  - Dissipation-induced W state in a Rydberg-atom-cavity system.
AB  - A dissipative scheme is proposed to prepare tripartite W state in a Rydberg-atom
      cavity system. It is an organic combination of quantum Zeno dynamics, Rydberg
      antiblockade, and atomic spontaneous emission to turn the tripartite W state into
      the unique steady state of the whole system. The robustness against the loss of
      cavity and the feasibility of the scheme are demonstrated thoroughly by the
      current experimental parameters, which lead to a high fidelity above 98%.

PMID- 29652329
TI  - 940  mW 1564  nm multi-longitudinal-mode and 440  mW 1537  nm single-longitudinal
      mode continuous-wave Er:Yb:Lu2Si2O7 microchip lasers.
AB  - An Er:Yb:Lu2Si2O7 microchip laser was constructed by placing a 1.2 mm thick, Y
      cut Er:Yb:Lu2Si2O7 microchip between two 1.2 mm thick sapphire crystals, in which
      input and output mirrors were directly deposited onto one face of each crystal.
      End-pumped by a continuous-wave 975.4 nm diode laser, a 1564 nm multi
      longitudinal-mode laser with a maximum output power of 940 mW and slope
      efficiency of 20% was realized at an absorbed pump power of 5.5 W when the
      transmission of output mirror was 2.2%. When the transmission of the output
      mirror was increased to 6%, a 1537 nm single-longitudinal-mode laser with a
      maximum output power of 440 mW and slope efficiency of 12% was realized at an
      absorbed pump power of 4.3 W. The results indicate that the Er:Yb:Lu2Si2O7
      crystal is a promising microchip gain medium to realize a single-longitudinal
      mode laser.

PMID- 29652330
TI  - Graphene-based broadband terahertz detector integrated with a square-spiral
      antenna.
AB  - Raising interest in terahertz radiation (loosely defined as the 0.1~10  THz
      frequency range) for the application-oriented issues in everyday life requires
      progressive development of fast, sensitive, and portable photodetectors. In this
      Letter, a broadband graphene-based terahertz detector with good integrability and
      sensitivity at room temperature is proposed. It is based on the chemical vapor
      deposited-grown graphene integrated with a square-spiral metal antenna which, on
      one hand, improves the efficiency for electromagnetic coupling and, on the other
      hand, facilitates the hot-electron photo-thermoelectric process for
      photodetection. Sensitivity over 28 V/W at room temperature and noise-equivalent
      power of less than 0.35  nW/Hz0.5 are demonstrated in reference to the incident
      power. The presented results appealingly open an alternative way to realize chip
      level graphene-based terahertz optoelectronics with good scalability and expected
      performance for targeted terahertz applications.

PMID- 29652331
TI  - Full-Stokes temporal imaging.
AB  - We developed a full-Stokes temporal imaging system which measures the Stokes
      vector of ultrafast signals as a function of time. The system is based on a time
      lens array where each time-lens in the array projects the signal on a different
      state of polarization.

PMID- 29652332
TI  - Compact lensless subpixel resolution large field of view microscope.
AB  - We report on a method to increase the spatial resolution in a compact lensless
      microscope. A compact side illumination is fabricated to illuminate the sample
      with a collimated beam by diffraction from a volume phase grating. The wavelength
      of a semi-conductor laser source (vertical-cavity surface-emitting laser) is
      tuned with the injection current to alter the illumination direction by
      wavelength selective diffraction from the volume phase grating. The angle tuning
      is such that several subpixel shifted digital inline holograms are obtained. The
      stack of holograms is then processed in a pixel super-resolution reconstruction
      algorithm. The amplitude of the sample is reconstructed with subpixel resolution
      over a large field of view (FOV). The technique is demonstrated on a 1951 USAF
      test target. A resolution of ~2.76  MUm, over a FOV of ~28  mm2, is demonstrated
      for a device of <2  cm height. The original pixel size was 5.2 MUm demonstrating
      the subpixel resolution.

PMID- 29652333
TI  - Enhancing terahertz magnetic near field induced by a micro-split-ring resonator
      with a tapered waveguide.
AB  - Substantial enhancement of terahertz magnetic near field achieved by the
      combination of a tapered metallic waveguide and a micro-split-ring resonator is
      demonstrated. The magnetic near field is probed directly via the magneto-optic
      sampling with a Tb3Ga5O12 crystal. The incident terahertz wave with a half-cycle
      waveform is generated by using the pulse-front tilting method. The magnetic near
      field at the resonant frequency is enhanced by more than 30 times through the
      combination of the waveguide and the resonator. The peak amplitude of the
      magnetic field with a damped oscillation waveform in the time domain is up to 0.4
      T. The resonant frequency can be tuned by adopting different resonator designs.
      The mechanism of the enhancement is analyzed by performing calculations based on
      the finite element method. The strong terahertz magnetic near field enables the
      excitation of large-amplitude spin dynamics and can be utilized for an ultrafast
      spin control.

PMID- 29652334
TI  - Microcavity-coupled fiber Bragg grating with tunable reflection spectra and speed
      of light.
AB  - After a fiber Bragg grating (FBG) is fabricated, the reflection spectrum of the
      FBG is generally not tunable without mechanical deformation or temperature
      adjustment. Here we present a microcavity-coupled FBG with both a tunable
      reflection lineshape and dispersion using electromagnetically induced
      transparency. The Fano interference of light in the FBG and the microcavity
      allows for dramatic modification of the reflection spectrum. The phase of the
      reflected spectrum is continuously tunable between 0 and 2pi to produce various
      Fano lineshapes. The dispersion of the output light is adjustable from normal
      dispersion to abnormal dispersion, consequently providing an adjustable speed of
      light. Additionally, it allows the FBG to switch from a notch filter to a
      bandpass filter at the resonant wavelength, which is not possible in a
      conventional uniform FBG.

PMID- 29652335
TI  - High-power 671  nm laser by second-harmonic generation with 93% efficiency in an
      external ring cavity.
AB  - Second-harmonic generation (SHG) is useful for obtaining single-frequency
      continuous-wave laser sources at various wavelengths for applications ranging
      from biology to fundamental physics. Using an external power-enhancement cavity
      is an effective approach to improve the frequency conversion efficiency. However,
      thermal effects limit the efficiency, particularly, in high-power operation.
      Therefore, reducing thermal effects is important when designing a cavity. This
      Letter reports the use of an external ring cavity for SHG, yielding a 5.2 W, 671
      nm laser light with a conversion efficiency of 93.8+/-0.8% which, to the best of
      our knowledge, is a new record of conversion efficiency for an external ring
      cavity. It is achieved using a 10 mm length periodically poled potassium titanyl
      phosphate crystal and a 65 MUm radius beam waist in the cavity so as to minimize
      thermal dephasing and thermal lensing. Furthermore, a method is developed to
      determine a conversion efficiency more accurately based on measuring the pump
      depletion using a photodiode detector and a maximum pump depletion up to 97% is
      recorded. In this method, the uncertainty is much less than that achieved in a
      common method by direct measuring with a power meter.

PMID- 29652336
TI  - Imaging through scattering layers exceeding memory effect range with spatial
      correlation-achieved point-spread-function.
AB  - We propose to measure intensity transmission matrices or point-spread-function
      (PSF) of diffusers via spatial-correlation, with no scanning or interferometric
      detection required. With the measured PSF, we report optical imaging based on the
      memory effect that allows tracking of moving objects through a scattering medium.
      Our technique enlarges the limited effective range of traditional imaging
      techniques based on the memory effect, and substitutes time-consuming iterative
      algorithms by a fast cross-correlation deconvolution method to greatly reduce
      time consumption for image reconstruction.

PMID- 29652337
TI  - Tailoring a nanofiber for enhanced photon emission and coupling efficiency from
      single quantum emitters.
AB  - We present a novel approach to enhance the spontaneous emission rate of single
      quantum emitters in an optical nanofiber-based cavity by introducing a narrow air
      filled groove into the cavity. Our results show that the Purcell factor for
      single quantum emitters inside the groove of the nanofiber-based cavity can be at
      least six times greater than for such an emitter on the fiber surface when using
      an optimized cavity mode and groove width. Moreover, the coupling efficiency of
      single quantum emitters into the guided mode of this nanofiber-based cavity can
      reach up to ~80% with only 35 cavity-grating periods. This new system has the
      potential to act as an all-fiber platform to realize efficient coupling of
      photons from single emitters into an optical fiber for quantum information
      applications.

PMID- 29652338
TI  - Mid-infrared frequency comb generation via cascaded quadratic nonlinearities in
      quasi-phase-matched waveguides.
AB  - We experimentally demonstrate a simple configuration for mid-infrared (MIR)
      frequency comb generation in quasi-phase-matched lithium niobate waveguides using
      the cascaded-chi(2) nonlinearity. With nanojoule-scale pulses from an Er:fiber
      laser, we observe octave-spanning supercontinuum in the near-infrared with
      dispersive wave generation in the 2.5-3 MUm region and intrapulse difference
      frequency generation in the 4-5 MUm region. By engineering the quasi-phase
      matched grating profiles, tunable, narrowband MIR and broadband MIR spectra are
      both observed in this geometry. Finally, we perform numerical modeling using a
      nonlinear envelope equation, which shows good quantitative agreement with the
      experiment-and can be used to inform waveguide designs to tailor the MIR
      frequency combs. Our results identify a path to a simple single-branch approach
      to mid-infrared frequency comb generation in a compact platform using commercial
      Er:fiber technology.

PMID- 29652339
TI  - Miniaturized single-fiber-based needle probe for combined imaging and sensing in
      deep tissue.
AB  - The ability to visualize structure while simultaneously measuring chemical or
      physical properties of a biological tissue has the potential to improve our
      understanding of complex biological processes. We report the first miniaturized
      single-fiber-based imaging+sensing probe capable of simultaneous optical
      coherence tomography (OCT) imaging and temperature sensing. An OCT lens is
      fabricated at the distal end of a double-clad fiber, including a thin layer of
      rare-earth-doped tellurite glass to enable temperature measurements. The high
      refractive index of the tellurite glass enables a common-path interferometer
      configuration for OCT, allowing easy exchange of probes for biomedical
      applications. The simultaneous imaging+sensing capability is demonstrated on rat
      brains.

PMID- 29652340
TI  - 87-W 1018-nm Yb-fiber ultrafast seeding source for cryogenic Yb: yttrium lithium
      fluoride amplifier.
AB  - We demonstrate a compact and robust Yb-fiber master-oscillator power-amplifier
      system operating at 1018 nm with 2.5-nm bandwidth and 1-ns stretched pulse
      duration. It produces 87-W average power and 4.9-MUJ pulse energy, constituting a
      powerful seed source for cryogenically cooled ultrafast Yb: yttrium lithium
      fluoride (Yb:YLF) amplifiers.

PMID- 29652341
TI  - Thermal-noise-limited higher-order mode locking of a reference cavity.
AB  - Higher-order mode locking has been proposed to reduce the thermal noise limit of
      reference cavities. By locking a laser to the HG02 mode of a 10-cm long all ultra
      low expansion (ULE) cavity and measuring its performance with the three-cornered
      hat method among three independently stabilized lasers, we demonstrate a thermal
      noise-limited performance of a fractional frequency instability of 4.9*10-16. The
      results match the theoretical models with higher-order optical modes. The
      achieved laser instability improves the all ULE short cavity results to a new low
      level.

PMID- 29652342
TI  - Enhanced broadband terahertz radiation generation near the reststrahlen band in
      sub-wavelength leaky-mode LiNbO3 waveguides.
AB  - The generation of terahertz (THz) radiation in a compact geometry is crucial for
      the implementation of on-chip, coherent THz radiation sources. Here, via
      numerical time-domain simulations, we show that LiNbO3 (LN) waveguides having sub
      wavelength core widths can provide highly efficient optical-to-THz radiation
      frequency conversion over short lengths. By exploiting the nonlinear
      susceptibility, chi33(2), enhancement of LN near its phonon reststrahlen band and
      utilizing THz leaky-mode guidance to minimize reststrahlen band absorption and
      improve phase matching, we show that broadband (0.2-11.6 THz) electric field
      pulses of 3.4 kV/cm can be generated at an optical-to-THz conversion efficiency
      of 2.5*10-4. These sub-wavelength leaky-mode waveguides provide a compact
      platform for wideband, coherent THz radiation sources.

PMID- 29652343
TI  - Single-shot phase-shifting incoherent digital holography with multiplexed
      checkerboard phase gratings.
AB  - Single-shot phase-shifting incoherent digital holography with multiplexed
      checkerboard phase gratings is proposed for acquiring holograms of moving
      objects. The gratings presented here play the following three roles: dividing the
      beams, modulating the curvature of spherical beams, and introducing different
      phase shifts. With the gratings of our proposed method, four individual holograms
      of a spatially incoherent light are formed on an image sensor. Therefore, it is
      possible to simultaneously capture four holograms and implement a phase-shifting
      technique. A proof-of-principle experiment was conducted to show the feasibility
      of the proposed method.

PMID- 29652344
TI  - Double anisotropic coherent backscattering of light.
AB  - A double anisotropic coherent backscattering cone was found. In contrast to the
      (single) anisotropic coherent backscattering, which was observed in liquid
      crystals, here, the long axis of the elongated structures changes its orientation
      with angular distance. We compared our results with the two-dimensional Fourier
      transform of spatially resolved reflectance measurements and found good
      agreement, which is predicted by the reciprocity thesis. Furthermore, a Monte
      Carlo model was applied to reproduce successfully the results of the experiment,
      whereas the double anisotropy is not predicted by diffusion models.

PMID- 29652345
TI  - Impact of mechanical stress induced in silica vacuum windows on laser-induced
      damage.
AB  - At the interface between vacuum and air, optical windows must keep their optical
      properties, despite being subjected to mechanical stress. In this Letter, we
      investigate the impact of such stress on the laser-induced damage of fused silica
      windows at the wavelength of 351 nm in the nanosecond regime. Different stress
      values, from 1 to 30 MPa, both tensile and compressive, were applied. No effect
      of the stress on the laser-induced damage was evidenced.

PMID- 29652346
TI  - Sub-bandgap photo-response of non-doped black-silicon fabricated by nanosecond
      laser irradiation.
AB  - Non-doped black silicon (b-Si) is fabricated on the surface layer of a near
      intrinsic Si substrate by nanosecond (ns) laser direct writing in an argon (Ar)
      atmosphere. The non-doped samples exhibit a near-unity sub-bandgap (1100~2500 
      nm) absorptance of more than 50%. Amazingly, the resistivity of the ns laser
      irradiated b-Si layer is about five orders of magnitude lower than that of the
      unprocessed Si substrate. The carrier density of the b-Si layer is about 1*1018 
      cm-3, according to the Hall effect measurement. Temperature-dependent Hall effect
      measurements show that the non-doped b-Si layer exhibits an energy level of 0.026
      eV below the conduction band minimum (CBM). At last, Si infrared photodiodes are
      made based on the difference of carrier concentration between the ns laser
      processed b-Si layer and the high-resistivity Si substrate. The responsivity of
      the b-Si photodiode for 1310 nm is up to 256  mA/W at a 10-V reverse bias, which
      is much higher than that of the reported pure Si bulk-structure photodiodes.

PMID- 29652347
TI  - High-gain and wide-band optical amplifications induced by a coupled excited state
      of organic dye molecules co-doped in polymer waveguide.
AB  - We investigated optical gain and lasing characteristics of a polymer thin film co
      doped with Rhodamine 6G and 4-(Dicyanomethylene)-2-methyl-6-(4
      dimethylaminostyryl)-4H-pyran dye molecules. By the co-doping of these dyes, the
      optical gain coefficient and its spectral range were enhanced and widened,
      respectively. These results cannot be accounted for by the linear combination of
      the optical gain properties of single-doped films. Owing to this high-gain and
      wide-band optical amplification property, a distributed feedback lasing with a
      low threshold of 70  MUJ/cm2 as well as a widely tunable wavelength range of 587
      613 nm was achieved. We attribute this amplification property of the co-doped
      film, which cannot be achieved with the single-doped films, to the appearance of
      a coupled excited state between the two molecules.

PMID- 29652348
TI  - Graphene electrodes for lithium-niobate electro-optic devices.
AB  - We propose and demonstrate the use of graphene electrodes for lithium-niobate
      electro-optic (EO) devices to exempt the need of incorporating a buffer layer
      between the waveguide and the electrodes. Using graphene electrodes, our
      experimental mode converter, based on an EO-generated long-period grating in a
      LiNbO3 waveguide, shows a reduction in the half-pi voltage by almost three times,
      compared with the conventional electrode design using metal. With the buffer
      layer exempted, the device fabrication process is also significantly simplified.
      The use of graphene electrodes is an effective approach to enhancing the
      efficiency of EO devices and, at the same time, reducing their fabrication cost.

PMID- 29652349
TI  - Chaotic Brillouin optical correlation-domain analysis.
AB  - We propose and experimentally demonstrate a chaotic Brillouin optical correlation
      domain analysis system for distributed fiber sensing. The utilization of a
      chaotic laser with a low coherence state ensures high spatial resolution. The
      experimental results demonstrate a 4 cm spatial resolution over a 906 m
      measurement range. The uncertainty in the measurement of the local Brillouin
      frequency shift is +/-1.2  MHz. The analysis of the expected spatial resolution
      and signal-to-noise ratio is also given.

PMID- 29652350
TI  - Continuous wave and ReS2 passively Q-switched Er : SrF2 laser at ~3  MUm.
AB  - We report on an efficient Er:SrF2 laser at 2.79 MUm. A continuous wave output
      power of 1.06 W was obtained with a slope efficiency of 41%, significantly
      exceeding the Stokes efficiency of 35%. Stable Q-switched laser operation was
      realized by using an ReS2 saturable absorber, generating an average output power
      of 0.58 W with a pulse duration of 508 ns at a repetition rate of 49 kHz,
      corresponding to a pulse energy of 12.1 MUJ.

PMID- 29652351
TI  - 65-fs Yb-doped all-fiber laser using tapered fiber for nonlinearity and
      dispersion management.
AB  - We implement an ultrafast Yb-doped all-fiber laser which incorporates tapered
      single-mode fibers for managing nonlinearity and dispersion. The tapered fiber
      placed in the oscillator cavity aims to broaden the optical spectrum of the
      intracavity pulse. At the oscillator output, we use another tapered fiber to
      perform pulse compression. The resulting 66.1-MHz Yb-doped all-fiber oscillator
      self-starts and generates 0.4-nJ, 65-fs pulses, which can serve as a compact and
      robust seed source for subsequent high-power, high-energy amplifiers.

PMID- 29652352
TI  - Efficient frequency conversion for cubic harmonic generation at 266  nm in
      centrosymmetric alpha-BBO crystal.
AB  - Direct third-harmonic generation (THG) is a third-order nonlinear process without
      the restriction to the symmetric characteristic of crystals. It is of great
      interest for setting up a chi(3) optical parametric oscillator which can be used
      in multiphoton quantum correlation. To obtain pure and strong THG, we proposed to
      elect the centrosymmetric crystal with delocalized pi bond as the nonlinear media
      during the frequency conversion process. An unprecedented cubic harmonic energy
      37.6 MUJ (average power ~37.6  mW, conversion efficiency ~2.5%) at 266 nm was
      generated in alpha-BBO crystal (not the beta-BBO), indicating direct THG in
      practical application. These results also demonstrated a succinct and efficient
      way to generate deep-UV laser and another development direction of nonlinear
      crystals in UV region.

PMID- 29652353
TI  - Side scattering shadow and energy concentration effects of epsilon-near-zero
      media.
AB  - By analytically and numerically investigating the near-field scattering
      properties of particles composed of epsilon-near-zero (ENZ) media, we reveal a
      unique scattering phenomenon which is hereby denoted as the side scattering
      shadow and energy concentration effect. The scattering of ENZ particles leads to
      the emergence of near-field "shadows," where the electric fields are
      significantly decreased to zero on two sides of the particle perpendicular to the
      incident direction. At the same time, the electric fields inside the particle are
      enhanced to a certain extent, indicating concentration of wave energy. These
      extraordinary behaviors can be well explained through the Mie scattering theory.
      Moreover, such unique effects robustly exist for isotropic and anisotropic ENZ
      particles of almost arbitrary shapes and with loss. We further demonstrate
      interesting applications of this effect, including the "quenching" of surface
      plasmons and the concentration of electromagnetic energy in the deep
      subwavelength scale. Our findings may inspire novel applications in
      nanophotonics.

PMID- 29652354
TI  - Efficient middle-infrared generation in LiGaS2 by simultaneous spectral
      broadening and difference-frequency generation.
AB  - We report a surprisingly broadband and efficient midinfrared pulse generation in
      LiGaS2 (Langasite, LGS) by invoking a simultaneous interplay of intrapulse
      difference-frequency generation, self-phase modulation, and dispersion. This
      cascaded mechanism expands the output bandwidth and output power at the same
      time. With 30-fs driving pulses centered at 1030-nm wavelength we obtain a
      broadband middle-infrared spectrum of 8-11 MUm with an LGS crystal as thick as 4
      mm, which is eight times longer than the walk-off length.

PMID- 29652355
TI  - Tunable dispersion compensation of quantum cascade laser frequency combs.
AB  - Compensating for group velocity dispersion is an important challenge to achieve
      stable midinfrared quantum cascade laser (QCL) frequency combs with large
      spectral coverage. We present a tunable dispersion compensation scheme consisting
      of a planar mirror placed behind the back facet of the QCL. Dispersion can be
      either enhanced or decreased depending on the position of the mirror. We
      demonstrate that the fraction of the comb regime in the dynamic range of the
      laser increases considerably when the dispersion induced by the Gires-Tournois
      interferometer compensates the intrinsic dispersion of the laser. Furthermore, it
      is possible to tune to the offset frequency of the comb with the Gires-Tournois
      interferometer while the repetition frequency is almost unaffected.

PMID- 29652356
TI  - Compressed supercontinuum probe for transient absorption microscopy.
AB  - Here, we combine three optical advancements to transient absorption microscopy in
      order to access the photodynamics in systems requiring stringent spatial and
      temporal resolution criteria. First, a broadband visible probe is generated by a
      commercial photonic crystal fiber. Second, a spatial light modulator-based pulse
      shaper is incorporated to reduce the pulse dispersion and improve temporal
      resolution. Third, 1.4 numerical aperture objectives for excitation and light
      collection provide optimal spatial resolution. The result of these improvements
      is a probe beam that spans 115 nm across the visible region yet maintains a ~100 
      fs instrument response at the sample position. We demonstrate the capabilities of
      this microscope by imaging polystyrene beads in a solution of IR-144 dye,
      revealing aggregated species at the bead surfaces.

PMID- 29652357
TI  - Dynamic mechanical analysis on fused polymer optical fibers: towards sensor
      applications.
AB  - This Letter presents, for the first time, to the best of our knowledge, the
      dynamic mechanical analysis of a polymer optical fiber (POF) that was previously
      damaged by the catastrophic fuse effect. The variation of the fiber Young's
      modulus was evaluated with respect to the increase of temperature, humidity, and
      frequency of strain cycles. The obtained data for the fused POF are compared with
      the ones for the same POF without the fuse effect. The results show the
      feasibility of the fused POF for sensor applications, such as strain and
      acceleration measurement, since it presents temperature sensitivity almost two
      times lower in temperatures between 26 degrees C and 90 degrees C and Young's
      modulus 2.3 times lower than those obtained with the bare fiber. The Young's
      modulus variation with the humidity is 1.5 MPa/%RH in a humidity range of 66-96%.
      In addition, the fused POF presented a variation of its dynamic modulus with the
      frequency increase four times lower than non-fused POFs on the range of 0.01
      100.00 Hz. These results pave the way for future applications of fused POFs as
      sensing elements.

PMID- 29652358
TI  - High-precision 3D surface topography measurement using high-stable multi
      wavelength digital holography referenced by an optical frequency comb.
AB  - High-stable, two-wavelength, digital holography referenced by an optical
      frequency comb is presented. The technique is demonstrated by using optical waves
      from an external cavity laser diode phase-locked to a mode-locked Er-doped fiber
      comb laser light. The mixed beat signal is stabilized at 30 MHz by a sensitive
      proportional integral derivative controller. The tunable continuous-waves
      stabilized with frequency uncertainty of 5*10-11 are employed to investigate
      large stepped structures.

PMID- 29652359
TI  - Cathodoluminescence hyperspectral analysis of whispering gallery modes in active
      semiconductor wedge resonators.
AB  - Whispering gallery mode resonators are key devices for integrated photonics.
      Despite their generalization in fundamental and applied science, information on
      spatial confinement of light in these structures is mostly retrieved from purely
      spectral analysis. In this work, we present a detailed spectral and spatial
      characterization of whispering gallery modes in active semiconductor microdisk
      resonators by use of hyperspectral cathodoluminescence. By comparing our
      experimental findings to finite element simulations, we demonstrate that the
      combination of spectral and spatial measurements enables unique identification of
      the modes and even reveals specific features of the microresonator geometry, such
      as a wedge profile.

PMID- 29652360
TI  - Gain-switched fiber laser at 3.55  MUm.
AB  - We report, to the best of our knowledge, the first demonstration of a gain
      switched fiber laser operating near 3.5 MUm. A dual-wavelength pumping scheme
      consisting of a 1976 nm Q-switched fiber system and a continuous-wave 976 nm
      laser diode were used to gain-switch a monolithic erbium-doped fluorozirconate
      fiber laser cavity at 3.552 MUm. Stable pulses were produced for repetition rates
      ranging between 15 and 20 kHz, and a record peak power of 204 W was achieved at
      15 kHz. A quenching phenomenon was also observed at 15 kHz for 1976 nm pulse
      energies beyond 180 MUJ.

PMID- 29652361
TI  - All-optical microwave oscillator based on semiconductor optical amplifier and
      stimulated Brillouin scattering.
AB  - An all-optical microwave oscillator is proposed and experimentally demonstrated.
      Based on a pure photonic feedback loop, this system can generate a photonic
      microwave signal without optical-electrical-optical conversion or any electrical
      microwave devices. A semiconductor optical amplifier implements the functions of
      microwave envelope detection and feedback modulation. Meanwhile, Brillouin
      selective sideband amplification is employed to lock oscillation frequency. In
      experiment, a good quality microwave signal with a frequency of 10.8 GHz is
      obtained. The tunability is also demonstrated by adjusting the Brillouin pump
      wavelength.

PMID- 29652362
TI  - Recording, erasing, and rewriting of ripples on metal surfaces by ultrashort
      laser pulses.
AB  - Recording, erasing, and rewriting of ripples are achieved by applying femtosecond
      laser pulses on tungsten surfaces. Ripples oriented perpendicular to the
      polarization direction of the writing beam can be recorded on a metal surface by
      exposing the sample to a series of linearly polarized pulses. When applying the
      second series of pulses with varied polarization direction on the same place, the
      original ripples can be erased, and new ripples are rewritten with the
      orientation perpendicular to the polarization of the second group of pulses. The
      simulation shows that when original ripples exist, laser intensity is focused
      above the grooves with polarization parallel to original ripples, which can erase
      the ripples. However, when the polarization is perpendicular to the existing
      ripples, laser intensity is almost confined in the grooves, which accelerates the
      formation of ripples.

PMID- 29652363
TI  - Imaging of cortical structures and microvasculature using extended-focus optical
      coherence tomography at 1.3  MUm.
AB  - Extended-focus optical coherence tomography (xf-OCT) is a variant of optical
      coherence tomography (OCT) wherein the illumination and/or detection modes are
      engineered to provide a constant diffractionless lateral resolution over an
      extended depth of field (typically 3 to 10* the Rayleigh range). xf-OCT systems
      operating at 800 nm have been devised and used in the past to image brain
      structures at high-resolution in vivo, but are limited to ~500  MUm in
      penetration depth due to their short illumination wavelength. Here we present an
      xf-OCT system optimized to an image deeper within the cortex by using a longer
      illumination central wavelength of 1310 nm. The system offers a lateral
      resolution of 3 and 6.5 MUm, over a depth of 900 MUm and >1.5  mm using a 10* and
      5* objective, respectively, in air. We characterize the system's resolution using
      microbeads embedded in PDMS and demonstrate its capabilities by imaging the
      cortical structure and microvasculature in anesthetized mice to a depth of ~0.8 
      mm. Finally, we illustrate the difference in penetration depths obtainable with
      the new system and an xf-OCT system operating at 800 nm.

PMID- 29652364
TI  - High-order orbital angular momentum mode generator based on twisted photonic
      crystal fiber.
AB  - High-order orbital angular momentum (OAM) modes, namely, OAM+5 and OAM+6, were
      generated and demonstrated experimentally by twisting a solid-core hexagonal
      photonic crystal fiber (PCF) during hydrogen-oxygen flame heating. Leaky orbital
      resonances in the cladding depend strongly on the twist rate and length of the
      helical PCF. Moreover, the generated high-order OAM mode could be a polarized
      mode. The secret of the successful observation of high-order modes is that leaky
      orbital resonances in the twisted PCF cladding have a high coupling efficiency of
      more than -20  dB.

PMID- 29652365
TI  - Generation of coherent extreme ultraviolet radiation from alpha-quartz using 50 
      fs laser pulses at a 1030  nm wavelength and high repetition rates.
AB  - Coherent extreme ultraviolet (EUV) radiation using high-harmonic generation (HHG)
      in alpha-quartz is demonstrated from 10 to 200 kHz, using 50 fs laser pulses at
      the center wavelength of 1030 nm. The EUV radiation extends beyond 25 eV in the
      nondamaging regime. The number of photons generated in a single harmonic order at
      15.6 eV is measured to be ~(3.5+/-2.5)*1010 per second which, to the best of our
      knowledge, is a first and record value reported to date using EUV HHG from
      solids. This Letter demonstrates one of the first all-solid-state EUV sources
      based on industrial-grade fiber lasers, enabling the possibility of bringing
      reliable EUV sources to the mass market.

PMID- 29652366
TI  - Ultra-low noise dual-frequency VECSEL at telecom wavelength using fully
      correlated pumping.
AB  - An ultra-low intensity and beatnote phase noise dual-frequency vertical-external
      cavity surface-emitting laser is built at telecom wavelength. The pump laser is
      realized by polarization combining two single-mode fibered laser diodes in a
      single-mode fiber, leading to a 100% in-phase correlation of the pump noises for
      the two modes. The relative intensity noise is lower than -140  dB/Hz, and the
      beatnote phase noise is suppressed by 30 dB, getting close to the spontaneous
      emission limit. The role of the imperfect cancellation of the thermal effect
      resulting from unbalanced pumping of the two modes in the residual phase noise is
      evidenced.

PMID- 29652367
TI  - Reconfigurable all-optical on-chip MIMO three-mode demultiplexing based on multi
      plane light conversion.
AB  - We present, to the best of our knowledge, the first experimental demonstration of
      reconfigurable all-optical on-chip multi-input-multi-output three-mode
      demultiplexing based on multi-plane light conversion. The demultiplexer consists
      of cascaded phase shifter arrays and multimode interference couplers integrated
      on a compact silicon chip. By optimizing the phase shifters, reconfigurable three
      mode demultiplexing is experimentally realized with wavelength-dependent loss of
      less than 3 dB and modal crosstalk of less than -10  dB over a 23 nm optical
      bandwidth. Error-free mode demultiplexing of 40 Gbps non-return-to-zero signal is
      also demonstrated.

PMID- 29652368
TI  - Ultralow-refractive-index optical thin films built from shape-tunable hollow
      silica nanomaterials.
AB  - Shape-tunable hollow silica nanomaterials, including hollow silica nano-spheres
      and nano-tadpoles, were synthesized with a one-step soft-templating method. A
      possible particle growth mechanism was proposed. Films were built from these
      shape-tunable hollow silica nanomaterials with refractive indices as low as
      1.045, which is, to the best of our knowledge, the third-lowest value ever
      reported so far. For the first time, the refractive indices of films were tuned
      by changing the morphology of building blocks. These films are intrinsically
      hydrophobic. Moreover, the process used to prepare these nanomaterials without
      the need for expensive equipment or any post-treatment is well suited for
      industrial production on large surfaces.

PMID- 29652369
TI  - Tunable nonlinear coherent perfect absorption with epsilon-near-zero plasmonic
      waveguides.
AB  - We propose a scheme to realize nonlinear coherent perfect absorption (CPA) at the
      nanoscale using epsilon-near-zero (ENZ) plasmonic waveguides. The general
      conditions to achieve CPA in a linear ENZ plasmonic waveguide are analyzed and
      presented. The proposed ENZ waveguides support an effective ENZ response at their
      cutoff frequency, where the CPA effect occurs under the illumination of two
      counterpropagating plane waves with equal amplitudes and appropriate phase
      distributions. In addition, the strong and uniform field enhancement inside the
      nanochannels of the waveguides at the ENZ resonance can efficiently boost Kerr
      nonlinearities, resulting in a new all-optical switching intensity-dependent CPA
      phenomenon that can be tunable with ultrafast speed. The proposed free-standing
      ENZ structures combine third-order nonlinear functionality with standing wave CPA
      interference effects in a nanoscale plasmonic configuration, thus leading to a
      novel degree of tunable light-matter interactions achieved in subwavelength
      regions. Our findings provide a new platform to efficiently excite nonlinear
      phenomena at the nanoscale and design tunable coherent perfect absorbers.

PMID- 29652370
TI  - Enhanced superlens imaging with loss-compensating hyperbolic near-field spatial
      filter.
AB  - Recently a coherent optical process called plasmon-injection (Pi) scheme, which
      employs an auxiliary source, has been introduced as a new technique to compensate
      losses in metamaterials. Here, a physical implementation of the Pi scheme is
      proposed for enhanced superlens imaging in the presence of absorption losses and
      noise. The auxiliary source is constructed by a high-intensity illumination
      (above 1  mW/MUm2) of the superlens integrated with a near-field spatial filter.
      The integrated system enables reconstruction of an object previously unresolvable
      with the superlens alone. This work elevates the viability of the Pi scheme as a
      strong candidate for loss compensation in near-field imaging systems without
      requiring nonlinear effects or gain media.

PMID- 29652371
TI  - Highly coherent free-running dual-comb chip platform.
AB  - We characterize the frequency noise performance of a free-running dual-comb
      source based on an erbium-doped glass chip running two adjacent mode-locked
      waveguide lasers. This compact laser platform, contained only in a 1.2 L volume,
      rejects common-mode environmental noise by 20 dB thanks to the proximity of the
      two laser cavities. Furthermore, it displays a remarkably low mutual frequency
      noise floor around 10  Hz2/Hz, which is enabled by its large-mode-area waveguides
      and low Kerr nonlinearity. As a result, it reaches a free-running mutual
      coherence time of 1 s since mode-resolved dual-comb spectra are generated even on
      this time scale. This design greatly simplifies dual-comb interferometers by
      enabling mode-resolved measurements without any phase lock.

PMID- 29652372
TI  - Quadratic nonlinear optical properties of the organic N-benzyl-2-methyl-4
      nitroaniline (BNA) biaxial crystal.
AB  - We performed the direct measurement of second harmonic generation and sum
      frequency generation phase-matching directions in the organic N-benzyl-2-methyl-4
      nitroaniline crystal over its visible and near-infrared transparency range. The
      fit of these data allowed us to refine the Sellmeier equations of the three
      principal refractive indices in this range. With these equations, we improved the
      calculated tuning curves of terahertz emission from a phase-matched difference
      frequency process. We also determined the absolute magnitude of the d24 nonlinear
      coefficient.

PMID- 29652373
TI  - Microwave-assisted Rydberg electromagnetically induced transparency.
AB  - We demonstrate electromagnetically induced transparency (EIT) in a four-level
      cascade-like system, where the two upper levels are Rydberg states coupled by a
      microwave field. A two-photon transition consisting of an off-resonant microwave
      field and an off-resonant optical field forms an effective coupling field to
      induce transparency of the probe light. We characterize the Rabi frequency of the
      effective coupling field, as well as the EIT microwave spectra. The results show
      that microwave-assisted EIT allows us to efficiently access Rydberg states with
      relatively high orbital angular momentum l=3, which is promising for the study of
      exotic Rydberg molecular states.

PMID- 29652374
TI  - Subwavelength light confinement and enhancement enabled by dissipative dielectric
      nanostructures.
AB  - Dissipative loss in optical materials is considered one of the major challenges
      in nano-optics. Here we show that, counter-intuitively, a large imaginary part of
      material permittivity contributes positively to subwavelength light enhancement
      and confinement. The Purcell factor and the fluorescence enhancement of
      dissipative dielectric bowtie nanoantennas, such as Si in ultraviolet (UV), are
      demonstrated to be orders of magnitude higher than their lossless dielectric
      counterparts, which is particularly favorable in deep UV applications where
      metals are plasmonically inactive. The loss-facilitated field enhancement is the
      result of a large material property contrast and an electric field discontinuity.
      These dissipative dielectric nanostructures can be easily achieved with a great
      variety of dielectrics at their Lorentz oscillation frequencies, thus having the
      potential to build a completely new material platform boosting light-matter
      interaction over broader frequency ranges, with advantages such as bio
      compatibility, CMOS compatibility, and harsh environment endurance.

PMID- 29652375
TI  - Edge enhancement by negative Poincare-Hopf index filters.
AB  - Phase and polarization are interrelated quantities, and hence polarization
      elements that perform like phase elements can be designed. In this Letter, we
      show that a polarizing element producing a negative Poincare-Hopf (PH) index beam
      can be used as a spatial filter to perform edge enhancement. Either isotropic or
      anisotropic edge enhancement can be achieved by polarization selection of the
      light that illuminates the sample. A conventional microscope imaging system is
      modified into a polarization-selective optical Fourier processor. Experimental
      results are presented to show that negative PH index filters, producing a set of
      orthogonal polarization distribution and their superpositions, can also be used
      for edge enhancement in optical signal processing.

PMID- 29652376
TI  - Quantized pseudomodes for plasmonic cavity QED.
AB  - We present a quantized pseudomode theory for solving system-level cavity quantum
      electrodynamics with quantum emitters coupled to plasmonic resonators. Exploiting
      the Green function response of a silver nanoparticle and an exact solution for
      the input-output coupling, we study the non-Markovian coupling regimes of multi
      mode vacuum Rabi oscillations and coherently pumped multi-photon resonances from
      the higher lying ladder states of collective plasmon modes. The nonlinear pumping
      regime also facilitates pronounced population inversion of a single two-level
      atom through multiphoton resonances dominated by dark plasmons.

PMID- 29652377
TI  - Single shot multi-wavelength phase retrieval with coherent modulation imaging.
AB  - A single shot multi-wavelength phase retrieval method is proposed by combining
      common coherent modulation imaging (CMI) and a low rank mixed-state algorithm
      together. A radiation beam consisting of multi-wavelength is illuminated on the
      sample to be observed, and the exiting field is incident on a random phase plate
      to form speckle patterns, which is the incoherent superposition of diffraction
      patterns of each wavelength. The exiting complex amplitude of the sample
      including both the modulus and phase of each wavelength can be reconstructed
      simultaneously from the recorded diffraction intensity using a low rank mixed
      state algorithm. The feasibility of this proposed method was verified with
      visible light experimentally. This proposed method not only makes CMI realizable
      with partially coherent illumination but also can extend its application to
      various traditionally unrelated fields, where several wavelengths should be
      considered simultaneously.

PMID- 29652378
TI  - Giant enhancement of Faraday rotation due to electromagnetically induced
      transparency in all-dielectric magneto-optical metasurfaces.
AB  - In this Letter we introduce a new class of Fano-resonant all-dielectric
      metasurfaces for enhanced, high figure of merit magneto-optical response. The
      metasurfaces are formed by an array of magneto-optical bismuth-substituted
      yttrium iron garnet nano-disks embedded into a low-index matrix. The strong field
      enhancement in the magneto-optical disks, which results in over an order of
      magnitude enhancement of Faraday rotation, is achieved by engineering two
      (electric and magnetic) resonances. It is shown that while enhancement of
      rotation also takes place for spectrally detuned resonances, the resonant
      excitation inevitably results in stronger reflection and low figure of merit of
      the device. We demonstrate that this can be circumvented by overlapping electric
      and magnetic resonances of the nanodisks, yielding a sharp electromagnetically
      induced transparency peak in the transmission spectrum, which is accompanied by
      gigantic Faraday rotation. Our results show that one can simultaneously obtain a
      large Faraday rotation enhancement along with almost 100% transmittance in an all
      dielectric metasurface as thin as 300 nm. A simple analytical model based on
      coupled-mode theory is introduced to explain the effects observed in first
      principle finite element method simulations.

PMID- 29652379
TI  - High-quality-factor multiple Fano resonances for refractive index sensing.
AB  - We design and numerically analyze a high-quality (Q)-factor, high modulation
      depth, multiple Fano resonance device based on periodical asymmetric paired bars
      in the near-infrared regime. There are four sharp Fano peaks arising from the
      interference between subradiant modes and the magnetic dipole resonance mode that
      can be easily tailored by adjusting different geometric parameters. The maximal Q
      factor can exceed 105 in magnitude, and the modulation depths DeltaT can reach
      nearly 100%. Combining the narrow resonance line-widths with strong near-field
      confinement, we demonstrate an optical refractive index sensor with a sensitivity
      of 370 nm/RIU and a figure of merit of 2846. This study may provide a further
      step in sensing, lasing, and nonlinear optics.

PMID- 29652380
TI  - Autofocusing optical-resolution photoacoustic endoscopy.
AB  - Photoacoustic (PA) endoscopy has the potential to diagnose early diseases in the
      gastrointestinal tract. For the first time, to our knowledge, we developed an
      autofocusing PA endoscope (AF-PAE) for the usually irregular gastrointestinal
      tract imaging to solve the deterioration of transverse resolution caused by the
      defocus scanning of the probe. The 9-mm-diameter AF-PAE probe integrated a 6-mm
      aspheric lens and 6-mm liquid lens to automatically adjust the optical focal
      length, and an unfocused ultrasonic transducer with a center frequency of 15 MHz
      is coaxially set for detecting PA signals. With this probe, the AF-PAE achieved a
      focus-shifting range from approximately 2 to 10 mm with high transverse
      resolution and image contrast in a 360 degrees  field of view. Phantom experiment
      and vasculature distribution of a resected rabbit rectum have been performed to
      demonstrate the imaging ability of the AF-PAE for potential clinical applications
      in colorectal vessel imaging and subsequent diagnosis.

PMID- 29652381
TI  - Tuning selective reflection of light by surface anchoring in cholesteric cells
      with oblique helicoidal structures.
AB  - Selective reflection of light by oblique helicoidal cholesteric (ChOH) can be
      tuned in a very broad spectral range by an applied electric field. In this
      Letter, we demonstrate that the peak wavelength of the selective reflection can
      be controlled by the surface alignment of the director in sandwich cells. The
      peak wavelength is blue-shifted when the surface alignment is perpendicular to
      the bounding plates and red-shifted when it is planar. The effect is explained by
      the electric field redistribution within the cell caused by a spatially varying
      heliconical ChOH structure. The observed phenomenon can be used in sensing
      applications.

PMID- 29652382
TI  - Octupole electrode pattern for tuning forks vibrating at the first overtone mode
      in quartz-enhanced photoacoustic spectroscopy.
AB  - The design, realization, and performance analysis of an octupole electrode
      pattern configuration intended for the optimization of the charge collection
      efficiency in quartz tuning forks (QTFs) vibrating at the first overtone in-plane
      flexural mode is reported. Two QTFs having the same geometry, but differing in
      the electrode pattern deposited on the QTF prongs, have been realized in order to
      study the influence of the electrode pattern on the resonance quality factor and
      electrical resistance. A standard quadrupole pattern (optimized for the
      fundamental mode) and an octupole electrode layout have been implemented.
      Although both QTFs show the same resonance quality factor for the first overtone,
      the octupole pattern provides a reduction of the QTF electrical resistance by
      more than four times. The sensing performance of the two QTFs has been compared
      by employing them in a mid-IR quartz-enhanced photoacoustic sensor (QEPAS) system
      targeting a water absorption line. When operating at the first overtone mode, the
      QTF with an octupole electrode pattern provides a QEPAS signal more than two
      times higher with respect to the QTF employing the standard quadrupole
      configuration.

PMID- 29652384
TI  - Spectral periodicity in soliton explosions on a broadband mode-locked Yb fiber
      laser using time-stretch spectroscopy.
AB  - Experimentally, we demonstrate, to the best of our knowledge, the first
      observation of periodic spectrum changing via soliton explosion in a passively
      mode-locked fiber laser by a nonlinear polarization evolution. Using time stretch
      to capture 7220 consecutive single-shot spectra over a 100 MUs time window in
      real time, the soliton explosions appear in a transition between two different
      mode-locking states. Simultaneous measurements of spectrum and pulse energy at
      three different output points in the laser cavity show that the soliton
      explosion's dynamics are related to residual dispersion. This study improves the
      understanding of pulse formation and evolution in the unstable mode-locking
      regime of lasers.

PMID- 29652383
TI  - Microparticle manipulation using femtosecond photonic nanojet-assisted laser
      cavitation.
AB  - We report the effect of laser cavitation in water initiated by femtosecond pulses
      confined into subwavelength volume of photonic nanojet of spherical
      microparticles. The effect of nanoscale optical breakdown was employed for
      controllable and nondestructive micromanipulation of silica microspheres. We
      combine this technique with optical trapping for cyclic particle movements and
      estimate a peak velocity and an acceleration acquired by microspheres propelled
      by nanojet cavitation. Our study provides a strategy for nondestructive optical
      micromanipulation, cavitation-assisted drug delivery, and laser energy
      transduction in microdevices.

PMID- 29652385
TI  - Multiple patterning of holographic photopolymers for increased refractive index
      contrast.
AB  - We demonstrate that multiple exposures of a two-component holographic
      photopolymer can quadruple the refractive index contrast of the material beyond
      the single-exposure saturation limit. Quantitative phase microscopy of isolated
      structures written by laser direct-write lithography is used to characterize the
      process. This technique reveals that multiple exposures are made possible by
      diffusion of the chemical components consumed during writing into the previously
      exposed regions. The ultimate index contrast is shown to be limited by the
      solubility of fresh components into the multiply exposed region.

PMID- 29652386
TI  - Automatic phase aberration compensation for digital holographic microscopy based
      on phase variation minimization.
AB  - We propose a numerical and totally automatic phase aberration compensation method
      in digital holographic microscopy. The phase aberrations are extracted in a
      nonlinear optimization procedure in which the phase variation of the
      reconstructed object wave is minimized. Not only phase curvature but also high
      order aberrations could be corrected without extra devices. The correction is
      directly carried out with the wrapped phase map, which is not affected by phase
      unwrapping or fitting errors. Numerical simulation proves that the proposed
      method is more accurate than the conventional surface fitting method without
      selecting a cell-free background. Experimental results demonstrate the
      availability of the proposed method in real-time analysis of living cells.

PMID- 29652387
TI  - On-chip multicomponent system made with an InGaN directional coupler.
AB  - An on-chip multicomponent system is implemented on a III-nitride-on-silicon
      platform by integrating a transmitter, InGaN waveguide, InGaN directional
      coupler, and receivers onto a single chip. The transmitter and the receiver share
      an identical InGaN/GaN multiple-quantum-well (MQW) diode structure and are
      produced by using the same wafer-level process flow. The receiver sensitively
      responds to the short-wavelength half of the emission spectrum of the
      transmitter, thus realizing the multicomponent system with the capability for
      inplane light communication. A SiO2 isolation layer is employed to decrease the p
      n junction capacitance, thus improving the modulation rate without modifying the
      MQW structure. The wire-bonded monolithic multicomponent system experimentally
      demonstrates inplane data transmission at 80 Mbps and spatial light communication
      at 100 Mbps, paving the way for diverse applications from on-chip power
      monitoring to inplane light communication in the visible light spectrum.

PMID- 29652388
TI  - Megahertz-resolution programmable microwave shaper.
AB  - A novel microwave shaper is proposed and demonstrated, of which the microwave
      spectral transfer function could be fully programmable with high resolution. We
      achieve this by bandwidth-compressed mapping a programmable optical wave-shaper,
      which has a lower frequency resolution of tens of gigahertz, to a microwave one
      with resolution of tens of megahertz. This is based on a novel technology of
      "bandwidth scaling," which employs bandwidth-stretched electronic-to-optical
      conversion and bandwidth-compressed optical-to-electronic conversion. We
      demonstrate the high resolution and full reconfigurability experimentally.
      Furthermore, we show the group delay variation could be greatly enlarged after
      mapping; this is then verified by the experiment with an enlargement of 194
      times. The resolution improvement and group delay magnification significantly
      distinguish our proposal from previous optics-to-microwave spectrum mapping.

PMID- 29652389
TI  - Time-domain measurement of optical activity by an ultrastable common-path
      interferometer.
AB  - We introduce a novel configuration for the broadband measurement of the optical
      activity of molecules, combining time-domain detection with heterodyne
      amplification. A birefringent common-path polarization-division interferometer
      creates two phase-locked replicas of the input light with orthogonal
      polarization. The more intense replica interacts with the sample, producing a
      chiral free-induction decay field, which interferes with the other replica,
      acting as a time-delayed phase-coherent local oscillator. By recording the delay
      dependent interferogram, we obtain by a Fourier transform both the circular
      dichroism and circular birefringence spectra. Our compact, low-cost setup accepts
      ultrashort light pulses, making it suitable for measurement of transient optical
      activity.

PMID- 29652390
TI  - Integrated catheter for simultaneous radio frequency ablation and optoacoustic
      monitoring of lesion progression.
AB  - Radio frequency (RF) catheter ablation is commonly used to eliminate
      dysfunctional cardiac tissue by heating via an alternating current. Clinical
      outcomes are highly dependent on careful anatomical guidance,
      electrophysiological mapping, and careful RF power titration during the
      procedure. Yet, current treatments rely mainly on the expertise of the surgeon to
      assess lesion formation, causing large variabilities in the success rate. We
      present an integrated catheter design suitable for simultaneous RF ablation and
      real-time optoacoustic monitoring of the forming lesion. The catheter design
      utilizes copper-coated multimode light guides capable of delivering both ablation
      current and near-infrared pulsed-laser illumination to the target tissue. The
      generated optoacoustic responses were used to visualize the ablation lesion
      formation in an ex-vivo bovine heart specimen in 3D. The presented catheter
      design enables the monitoring of ablation lesions with high spatiotemporal
      resolution while the overall therapy-monitoring approach remains compatible with
      commercially available catheter designs.

PMID- 29652391
TI  - 18  km low-crosstalk OAM + WDM transmission with 224 individual channels enabled
      by a ring-core fiber with large high-order mode group separation.
AB  - The space domain is regarded as the only known physical dimension of lightwaves
      left to be exploited for optical communications. Very recently, much research
      effort has been devoted to using orbital angular momentum (OAM) spatial modes to
      increase the transmission capacity in fiber-optic communications. However, long
      distance low-crosstalk high-order OAM multiplexing transmission in fiber is quite
      challenging. Here we design and fabricate a graded-index ring-core fiber to
      effectively suppress radially high-order modes and greatly separate high-order
      OAM mode groups. By exploiting high-order OAM mode group multiplexing, together
      with wavelength-division multiplexing (WDM), i.e., 12.5 Gbaud 8-array quadrature
      amplitude modulation (8-QAM) signals over OAM+4 and OAM+5 modes on 112 WDM
      channels (224 individual channels), we experimentally demonstrate 8.4 Tbit/s data
      transmission in an 18 km OAM fiber with low crosstalk. Multiple-input multiple
      output digital signal processing is not required in the experiment because of the
      large high-order mode group separation of the OAM fiber. The demonstrations may
      open a door to find more fiber-optic communication and interconnect applications
      exploiting high-order OAM modes.

PMID- 29652392
TI  - Orbital angular momentum mode multiplexed transmission in heterogeneous few-mode
      and multi-mode fiber network.
AB  - Mode-division multiplexing (MDM), which employs the spatial modes of light as
      information carriers, has been widely investigated to increase the transmission
      capacity. Few-mode fibers (FMFs) and multi-mode fibers (MMFs) have been used for
      MDM fiber transmission. One of the MDM techniques known as twisted light
      multiplexing using orbital angular momentum (OAM) modes has recently attracted
      increasing interest. In this Letter, by splicing two FMFs together with a
      conventional OM3 MMF, we propose and demonstrate OAM-based MDM in a heterogeneous
      fiber-optic network, i.e., two OAM mode (OAM01 and OAM-11) multiplexing
      transmission in the heterogeneous FMFs and MMF network. We transmit 20-Gbit/s
      quadrature phase shift keying signals over two OAM modes in different mode groups
      without multiple-input multiple-output equalization techniques and achieve less
      than 2.8 dB optical signal-to-noise ratio penalties at a bit-error rate of 2*10
      3. The experimental results show favorable transmission performance of OAM-based
      MDM in heterogeneous FMFs and MMF network compared to the one in FMF.

PMID- 29652393
TI  - Compact flexible multifrequency splitter based on plasmonic graded metallic
      grating arc waveguide.
AB  - A compact flexible multifrequency splitter based on an arc waveguide constructed
      of plasmonic metallic grating structures with graded-height T-grooves is proposed
      and studied. The dispersion curves and cutoff frequencies of the plasmonic
      grating waveguides with different T-groove metallic grating heights are
      different. The guided spoof surface plasmonic polariton waves at different
      frequencies can be localized at dissimilar angles along the graded grating arc
      waveguide. The output flexibility at an arbitrary groove for different
      frequencies is realized by introducing an additional symmetrical T-groove
      structure as an output. The compact four-, seven-, and eight-output frequency
      splitters demonstrate its flexible multifrequency separation capability at
      different output angle locations, while the dimensional size of the frequency
      splitters is not increased. Measurement results at the microwave frequency
      display excellent agreement with numerical simulation results.

PMID- 29652394
TI  - Widely tunable, high slope efficiency waveguide lasers in a Yb-doped glass chip
      operating at 1  MUm.
AB  - Ultrafast laser inscribed waveguide lasers can lead to highly efficient and
      compact optical devices. This Letter reports an average lasing efficiency of
      65%+/-2.5% from a multi-waveguide 2.5 mol. % ytterbium-doped ZrF4-BaF2-LaF3-AlF3
      NaF (Yb:ZBLAN) chip in an extended-cavity configuration. A maximum output power
      of 750 mW with a lasing efficiency of 68% is also achieved. A monolithic end
      coupled configuration reached a maximum output power of 784 mW with a lasing
      efficiency of 70%. The lasing wavelength is tuned from 1001 to 1045 nm in a
      Littrow configured cavity. A beam propagation factor of the lowest-order
      transverse-mode output was routinely achieved with an M2 of 1.15.

PMID- 29652395
TI  - Resolution enhancement for fiber bundle imaging using maximum a posteriori
      estimation.
AB  - We propose a new framework to jointly improve spatial resolution and remove fixed
      structural patterns for coherent fiber bundle imaging systems, based on inverting
      a principled forward model. The forward model maps a high-resolution
      representation to multiple images modeling random probe motions. We then apply a
      point spread function to simulate low-resolution figure bundle image capture. Our
      forward model also uses a smoothing prior. We compute a maximum a posteriori
      (MAP) estimate of the high-resolution image from one or more low-resolution
      images using conjugate gradient descent. Unique aspects of our approach include
      (1) supporting a variety of possible applicable transformations; (2) applying
      principled forward modeling and MAP estimation to this domain. We test our method
      on data synthesized from the USAF target, data captured from a transmissive USAF
      target, and data from lens tissue. In the case of the USAF target and 16 low
      resolution captures, spatial resolution is enhanced by a factor of 2.8.

PMID- 29652396
TI  - Noise-like pulses with a 14.5 fs spike generated in an Yb-doped fiber nonlinear
      amplifier.
AB  - We demonstrate noise-like pulses with a 14.5 fs spike generated in an Yb-doped
      fiber nonlinear amplifier after compression, while the pedestal has a width of
      3.70 ps. This Yb-doped fiber nonlinear amplifier is seeded by dissipative
      solitons. With an average output power of 5 W, the single pulse energy is
      approximately 200 nJ at a repetition rate of 24.65 MHz. Mathematical research
      based on the coupled nonlinear Schrodinger equations about the generation and the
      compressibility of the noise-like pulses is also carried out.

PMID- 29652398
TI  - Spin-orbital angular momentum tomography of a chiral plasmonic lens using leakage
      radiation microscopy.
AB  - Based on the spin-dependent directional coupling of surface plasmons (SPs) by ?
      shaped antennas, ring-shaped structures built with such antennas have potential
      applications for optical tweezers and optical switch technology. In this Letter,
      we introduce an optical method for realizing a complete polarization tomography
      of coupled SP fields by such a chiral-planar structure. We use a far-field
      optical approach, namely leakage radiation microscopy (LRM), to map the SPs
      propagation and polarization. Here, we fully analyze the polarization state of
      the generated SPs inside the vortex lens structure. In addition, we provide a
      theoretical model which agrees well with the experimental results.

PMID- 29652397
TI  - Three-photon fluorescence microscopy with an axially elongated Bessel focus.
AB  - Volumetric imaging tools that are simple to adopt, flexible, and robust are in
      high demand in the field of neuroscience, where the ability to image neurons and
      their networks with high spatiotemporal resolution is essential. Using an axially
      elongated focus approximating a Bessel beam, in combination with two-photon
      fluorescence microscopy, has proven successful at such an endeavor. Here, we
      demonstrate three-photon fluorescence imaging with an axially extended Bessel
      focus. We use an axicon-based module that allowed for the generation of Bessel
      foci of varying numerical apertures and axial lengths, and apply this volumetric
      imaging tool to image mouse brain slices and for in vivo imaging of the mouse
      brain.

PMID- 29652399
TI  - Parametric spectrotemporal analyzer based on four-wave mixing Bragg scattering.
AB  - A parametric spectro-temporal analyzer (PASTA) has been demonstrated as an
      ultrafast single-shot spectral analyzing technique. However, the relatively
      complex system configuration and the limited wavelength measurement range limit
      its practical application. In this work, a new system design utilizing a four
      wave mixing Bragg scattering (FWM-BS) process is presented that significantly
      simplifies the implementation. More importantly, owing to the large parametric
      conversion bandwidth of the FWM-BS process, the maximum wavelength measurement
      range has been expanded to around 30 nm. In addition, the detection sensitivity
      is also enhanced by 10 dB. Our work thus represents a critical step in realizing
      the practical application of the PASTA technique.

PMID- 29652401
TI  - Kramers-Kronig detection with Brillouin-amplified virtual carrier: publisher's
      note.
AB  - This publisher's note corrects an error in the title in Opt. Lett.43, 1367
      (2018)OPLEDP0146-959210.1364/OL.43.001367.

PMID- 29652400
TI  - Emission beyond 4  MUm and mid-infrared lasing in a dysprosium-doped indium
      fluoride (InF3) fiber.
AB  - Optical emission from rare-earth-doped fluoride fibers has thus far been limited
      to less than 4 MUm. We extend emission beyond this limit by employing an indium
      fluoride (InF3) glass fiber as the host, which exhibits an increased infrared
      transparency over commonly used zirconium fluoride (ZBLAN). Near-infrared pumping
      of a dysprosium-doped InF3 fiber results in broad emission centered around 4.3
      MUm, representing the longest emission yet achieved from a fluoride fiber. The
      first laser emission in an InF3 fiber is also demonstrated from the 3 MUm
      dysprosium transition. Finally, a frequency domain excited state lifetime
      measurement comparison between fluoride hosts suggests that multiphonon effects
      are significantly reduced in indium fluoride fiber, paving the way to more
      efficient, longer wavelength lasers compared to ZBLAN fibers.

PMID- 29652402
TI  - Broadening the optical bandwidth of quantum cascade lasers using RF noise current
      perturbations.
AB  - We report on the broadening of the optical bandwidth of a distributed feedback
      quantum cascade laser (QCL) caused by the application of radio frequency (RF)
      noise to the injection current. The broadening is quantified both via Lamb-dip
      spectroscopy and the frequency noise power spectral density (PSD). The linewidth
      of the unperturbed QCL (emitting at ~5.3  MUm) determined by Lamb-dip
      spectroscopy is 680+/-170  kHz, and is in reasonable agreement with the linewidth
      of 460+/-40  kHz estimated by integrating the PSD measured under the same laser
      operating conditions. Measurements with both techniques reveal that by mixing the
      driving current with broadband RF noise the laser lineshape was reproducibly
      broadened up to ca 6 MHz with an increasing Gaussian contribution. The effects of
      linewidth broadening are then demonstrated in the two-color coherent transient
      spectra of nitric oxide.

PMID- 29652403
TI  - Ultra-broadband 2 * 2 adiabatic 3  dB coupler using subwavelength-grating
      assisted silicon-on-insulator strip waveguides.
AB  - We report on a compact, ultra-broadband, 2*2 adiabatic 3 dB coupler using silicon
      on-insulator (SOI) strip waveguides assisted by sub-wavelength gratings (SWGs).
      In our device, two tapered SWG-assisted SOI strip waveguides achieve an adiabatic
      mode evolution of the two lowest-order transverse electric modes, in a two
      waveguide system, for broadband 3 dB power splitting. Theory predicts that the
      proposed coupler will operate from 1200 nm to 1700 nm. We have been able to
      measure the performance of a device with a 15 MUm long mode evolution region that
      achieves even, broadband power splitting over the 185 nm wavelength range of our
      tunable laser with an imbalance of less than +/-0.3  dB and with low average
      excess losses of <0.11  dB.

PMID- 29652404
TI  - Terahertz emission from metal nanoparticle array.
AB  - We demonstrate theoretically that ultrafast heating of metal nanoparticles by the
      laser pulse should lead to the generation of coherent terahertz (THz) radiation
      during the heat redistribution process. It is shown that after the femtosecond
      laser pulse action, the time-dependent gradient of the electronic temperature
      induces low-frequency particle polarization with the characteristic timescale of
      about fractions of a picosecond. In the case of the directed metallic pattern,
      the THz pulse waveform can be controlled by changing the geometry of the
      particle. The proposed THz generation mechanism can be the basis for
      interpretation of recent experiments with metallic nanoparticles and
      nanostructures.

PMID- 29652405
TI  - Quantum annealing versus classical machine learning applied to a simplified
      computational biology problem.
AB  - Transcription factors regulate gene expression, but how these proteins recognize
      and specifically bind to their DNA targets is still debated. Machine learning
      models are effective means to reveal interaction mechanisms. Here we studied the
      ability of a quantum machine learning approach to predict binding specificity.
      Using simplified datasets of a small number of DNA sequences derived from actual
      binding affinity experiments, we trained a commercially available quantum
      annealer to classify and rank transcription factor binding. The results were
      compared to state-of-the-art classical approaches for the same simplified
      datasets, including simulated annealing, simulated quantum annealing, multiple
      linear regression, LASSO, and extreme gradient boosting. Despite technological
      limitations, we find a slight advantage in classification performance and nearly
      equal ranking performance using the quantum annealer for these fairly small
      training data sets. Thus, we propose that quantum annealing might be an effective
      method to implement machine learning for certain computational biology problems.

PMID- 29652406
TI  - Individual Importance Weighting of Domain Satisfaction Ratings does Not Increase
      Validity.
AB  - Bottom-up models of life satisfaction are based on the assumption that
      individuals judge the overall quality of their lives by aggregating information
      across various life domains, such as health, family, and income. This aggregation
      supposedly involves a weighting procedure because individuals care about
      different parts of their lives to varying degrees. Thus, composite measures of
      well-being should be more accurate if domain satisfaction scores are weighted by
      the importance that respondents assign to the respective domains. Previous
      studies have arrived at mixed conclusions about whether such a procedure actually
      works. In the present study, importance weighting was investigated in the Panel
      Study of Income Dynamics (PSID; N = 5,049). Both weighted composite scores and
      moderated regression analyses converged in producing the conclusion that
      individual importance weights did not result in higher correlations with the
      outcome variable, a global measure of life satisfaction. By contrast, using
      weights that vary normatively across domains (e.g., assigning a larger weight to
      family satisfaction than to housing satisfaction for all respondents)
      significantly increased the correlation with global life satisfaction (although
      incremental validity was rather humble). These results converge with findings
      from other fields such as self-concept research, where evidence for individual
      importance weighting seems elusive as best.

PMID- 29652407
TI  - Resting-Exercise Salivary Cortisol Responses: Detecting the Magnitude of Hormonal
      Change Over Time.
AB  - This study investigated the validity of salivary cortisol responses to reflect
      blood cortisol responses relative to the magnitude of change observed over time
      in the hormone. Male subjects (n=25) conducted four experimental sessions (ES)
      where blood (B) and saliva (S) were obtained before (PS) and after (PoS) a 30 min
      resting control, 40%, 60%, and 80% of maximal aerobic capacity (VO2max) exercise
      ES. B and S specimens were analyzed by standard biochemical procedures. Hormonal
      concentrations changes were assessed by using absolute delta (DA) values (PoS -
      PS) and percent change (PC) calculations ((PoS-PS)/PS * 100) for each B and S
      specimen. Subsequent DA and PC values were correlated (Pearson) for each B-S
      specimen pairing (n=100; n=25 * 4 ES). Results indicate the magnitude of change
      (PoS vs. PS) in S cortisol is more valid and strongly associated (p<0.001) with
      corresponding B changes (the "gold standard") when expressing the data as delta
      values using absolute hormonal concentrations as compared to percent change
      expression.

PMID- 29652408
TI  - Correction to: Physico-chemical oxidative cleavage strategy facilitates the
      degradation of recalcitrant crystalline cellulose by cellulases hydrolysis.
AB  - [This corrects the article DOI: 10.1186/s13068-018-1016-0.].

PMID- 29652409
TI  - Erratum to: Linear Analysis of Autonomic Activity and Its Correlation with
      Creatine Kinase-MB in Overt Thyroid Dysfunctions.
AB  - [This corrects the article DOI: 10.1007/s12291-017-0659-0.].

PMID- 29652410
TI  - Corrigendum: Compound Heterozygous Variants in the Coiled-Coil Domain Containing
      40 Gene in a Chinese Family With Primary Ciliary Dyskinesia Cause Extreme
      Phenotypic Diversity in Cilia Ultrastructure.
AB  - [This corrects the article on p. 23 in vol. 9, PMID: 29456554.].

PMID- 29652411
TI  - The implementation of NEMS GFS Aerosol Component (NGAC) Version 1.0 for global
      dust forecasting at NOAA/NCEP.
AB  - The NOAA National Centers for Environmental Prediction (NCEP) implemented NEMS
      GFS Aerosol Component (NGAC) for global dust forecasting in collaboration with
      NASA Goddard Space Flight Center (GSFC). NGAC Version 1.0 has been providing 5
      day dust forecasts at 1 degrees *1 degrees  resolution on a global scale, once
      per day at 00:00 Coordinated Universal Time (UTC), since September 2012. This is
      the first global system capable of interactive atmosphere aerosol forecasting at
      NCEP. The implementation of NGAC V1.0 reflects an effective and efficient
      transitioning of NASA research advances to NCEP operations, paving the way for
      NCEP to provide global aerosol products serving a wide range of stakeholders as
      well as to allow the effects of aerosols on weather forecasts and climate
      prediction to be considered.

PMID- 29652412
TI  - Correction to: MicroRNA-214-3p inhibits proliferation and cell cycle progression
      by targeting MELK in hepatocellular carcinoma and correlates cancer prognosis.
AB  - [This corrects the article DOI: 10.1186/s12935-017-0471-1.].

PMID- 29652413
TI  - Breaking up with ATM.
AB  - ATM kinase is a master regulator of the DNA damage response (DDR). A recently
      published report from the d'Adda di Fagagna laboratory1 sheds a light onto our
      understanding of ATM activation. In this short-commentary we will expand on this
      and other work to perceive better some of the aspects of ATM regulation.

PMID- 29652414
TI  - An electron transfer driven magnetic switch: ferromagnetic exchange and spin
      delocalization in iron verdazyl complexes.
AB  - The verdazyl 'pincer' ligand, 1-isopropyl-3,5-dipyridyl-6-oxoverdazyl (dipyvd),
      coordinates iron to form a series of pseudooctahedral coordination compounds
      [Fe(dipyvd)2]n+ (n = 0-3). In the case where n = 2, the molecular geometry and
      physical and spectral properties are consistent with a low spin (S = 0) iron(ii)
      ion coordinated by two ferromagnetically coupled radical ligands. Upon one
      electron reduction, the room temperature effective magnetic moment of the complex
      jumps from MUeff = 2.64 to MUeff = 5.86 as a result of spin crossover of the iron
      atom combined with very strong ferromagnetic coupling of the remaining ligand
      centered unpaired electron with the metal center. The sign of the exchange is
      opposite to that observed in other high spin iron/radical ligand systems and
      appears to be a result of delocalization of the ligand unpaired electron across
      the whole molecule. The large change in magnetic properties, combined with a
      delocalized electronic structure and accessible redox potentials, suggests the
      utility of this and related systems in the development of novel molecular
      spintronic devices.

PMID- 29652415
TI  - A study of polymer chain diffusion by surface enhanced Raman: effects of
      plasmonic substrate topology.
AB  - We report on a new methodology to track chain interdiffusion between polymer
      slabs based on Raman enhanced by plasmonic substrates. Diffusion is studied in a
      deuterated-polystyrene/polystyrene (dPS/PS) polymer pair, designed to provide a
      well-characterized diffusion behavior. The bilayer, 160 nm thick in total, is
      supported on a plasmonic substrate that provides local amplification of Raman
      signals in sample regions of close proximity to it. Gold-based substrates with
      structures of inverted pyramids, spherical nanoparticles and tipped pillars were
      investigated. Interdiffusion between dPS and PS is promoted upon annealing and
      followed in situ by dynamic spectral acquisition. A simple model that describes
      the coupling between the sampled region arising from the plasmonic effect and the
      diffusion process is employed to interpret spectral evolution data. It is shown
      that a highly regular topology and surface continuity are key features of the
      plasmonic substrate in order to provide reliable results. With pyramidal
      substrates, the most suitable substrates for this application, data are
      consistent with diffusion coefficients in the range 10-13-10-15 cm2 s-1 and
      dimensions of sampled regions below 40 nm. The strategy provides a reliable
      labeling-free technique to investigate polymer interdiffusion on the nanoscale.

PMID- 29652416
TI  - Dynamics of liquid crystalline phase transition in sedimenting platelet-like
      particles.
AB  - When a suspension of platelet-like particles sediment in a closed container, the
      particles undergo isotropic-nematic phase transition (I-N transition), and there
      appears a clear interface between the isotropic phase and the nematic phase.
      Usually the interface moves from bottom to top since the nematic phase appears
      and grows at the bottom, but it has been observed that in some situations the
      interface moves from top to bottom. Here, we study the dynamics of the interface
      by solving the non-equilibrium diffusion equation for the concentration of
      platelet-like particles, and show that the I-N interface can move upward (rising
      interface) or downward (falling interface) depending on whether the initial
      concentration is less than the critical concentration of I-N transition or more
      than it. We give a simple analysis theory for the motion of the interface in each
      case, which agrees well with the numerical calculations. We also show that the
      numerical results are in reasonable agreement with existing experimental
      measurements.

PMID- 29652417
TI  - Nanoparticle packing within block copolymer micelles prepared by the interfacial
      instability method.
AB  - The interfacial instability method has emerged as a viable approach for
      encapsulating high concentrations of nanoparticles (NPs) within morphologically
      diverse micelles. In this method, transient interfacial instabilities at the
      surface of an emulsion droplet guide self-assembly of block co-polymers and NP
      encapsulants. Although used by many groups, there are no systematic
      investigations exploring the relationship between NP properties and micelle
      morphology. Here, the effect of quantum dot (QD) and superparamagnetic iron oxide
      NP (SPION) concentration on the shape, size, and surface deformation of initially
      spherical poly(styrene-b-ethylene oxide) (PS-b-PEO) micelles was examined. Multi
      NP encapsulation and uniform dispersion within micelles was obtained even at low
      NP concentrations. Increasing NP concentration initially resulted in larger
      numbers of elongated micelles and cylinders with tightly-controlled diameters
      smaller than those of spherical micelles. Beyond a critical NP concentration,
      micelle formation was suppressed; the dominant morphology became densely-loaded
      NP structures that were coated with polymer and exhibited increased
      polydispersity. Transmission electron microscopy (TEM) and small angle X-ray
      scattering (SAXS) revealed that NPs in densely-loaded structures can be well
      ordered, with packing volume fractions of up to 24%. These effects were enhanced
      in magnetic composites, possibly by dipole interactions. Mechanisms governing
      phase transitions triggered by NP loading in the interfacial instability process
      were proposed. The current study helps establish and elucidate the active role
      played by NPs in directing block copolymer assembly in the interfacial
      instability process, and provides important guiding principles for the use of
      this approach in generating NP-loaded block copolymer composites.

PMID- 29652418
TI  - Go to Facebook! Kardiologia Polska is there.

PMID- 29652419
TI  - Tricuspid valve regurgitation: still struggling with the who and when.

PMID- 29652421
TI  - Arterial hypertension after age 65: from epidemiology and pathophysiology to
      therapy Do we know where we stand?
AB  - Arterial hypertension is a prevalent disease with great harming potential. After
      the age of 55 years the remaining lifetime risk of hypertension amounts to 90%.
      Despite the constant advances some important issues such as the cut-off blood
      pressure for the initiation of antihypertensive therapy or the therapeutic goal
      are debated. In this review, we present - based on the available literature - the
      current concepts concerning the pathophysiology, epi-demiology and
      antihypertensive therapy in patients aged 65 years or older. The pathophysiology
      of hypertension in older patients in principle rests on stiffening of large
      conduit arteries, which leads to greater systolic and lower diastolic blood
      pressure. This in most older patients results in isolated systolic hypertension.
      Additionally most of these patients have low-renin hypertension. Data from large
      scale clinical trials indicate that therapy of such individuals with thiazide
      like diuretics and long-acting dihydropiridine calcium channel blockers as first
      line medications reduces risk of complications. Based on results of recently
      published trials, meta-analyses, and prospective observations, the optimal on
      treatment blood pressure values for most older hypertensive patients should be
      set within the 130-139 mmHg range. At present, lower values of standard office
      blood pressure in this group of patients have not been shown to be associ-ated
      with additional benefits, and may be associated with a greater risk of adverse
      events. In conclusion, we recommend that for most patients aged 65 years or more,
      standard office systolic blood pressure should be cautiously reduced to within
      140 and 130 mmHg, preferably with a thiazide-like diuretic, long acting
      dihydropiridine calcium channel blocker or their combination.

PMID- 29652420
TI  - Bivalirudin bewilderment.

PMID- 29652422
TI  - Number of erythrocytes as a prognostic marker in patients undergoing heart valve
      surgery.

PMID- 29652423
TI  - The influence of metabolic syndrome coexistence on the prognosis of patients with
      heart failure without atrial fibrillation. Analysis of Polish data from the pilot
      survey for the ESC Heart Failure Registry.

PMID- 29652424
TI  - Pre-discharge test may worsen cognitive functioning in patients with implantable
      cardioverter-defibrillator.

PMID- 29652425
TI  - [Risk factors for cardiac device-related infection during two-year follow-up: a
      retrospective analysis].

PMID- 29652426
TI  - The effects of a high-fat diet on left ventricular fibrosis.

PMID- 29652427
TI  - The network of invasive cardiology facilities in Poland in 2016 (data from the
      ORPKI Polish National Registry).

PMID- 29652428
TI  - [Heart failure manifestation of carcinoid tricuspid dysfunction].

PMID- 29652429
TI  - Successful rotational atherectomy for abdominal aortic stenosis with severe
      calcification in a patient treated with transfemoral transcatheter aortic valve
      implantation.

PMID- 29652430
TI  - Immediate surgical repair of left ventricular wall rupture complicating ST
      segment elevation myocardial infarction.

PMID- 29652431
TI  - Use of three-dimensional echocardiography for monitoring of tricuspid valve
      endocarditis treatment with a novel extracellular matrix cylinder reconstruction.

PMID- 29652432
TI  - A rare case of right corkscrew cervical aortic arch associated with retrotracheal
      aberrant left brachiocephalic vein.

PMID- 29652433
TI  - Vasculitis or coronary atherosclerosis? Optical coherence tomography images in
      polyarteritis nodosa.

PMID- 29652434
TI  - The Columbus of cardiovascular surgery. A tribute to Francis Fontan (1929-2018).

PMID- 29652435
TI  - Mediterranean agro-industrial wastes as valuable substrates for lignocellulolytic
      enzymes and protein production by solid-state fermentation.
AB  - BACKGROUND: Mediterranean agro-food industries (such as wineries, breweries and
      olive mills) dispose of great amounts of waste. This generates environmental
      problems, and the waste has a low nutritional value for use as animal feed. In
      this sense, solid-state fermentation (SSF) can increase the nutritional value of
      these wastes and simultaneously produce lignocellulolytic enzymes. RESULTS: All
      fermented wastes were enriched in protein by the three fungi studied. Aspergillus
      ibericus was the fungus with the biggest increase of protein, which ranged from
      1.4 times to 6.2 times with respect to unfermented wastes. Likewise, A. ibericus
      achieved the maximum cellulase and xylanase activities. The relationships among
      substrates composition, fungi used and SSF performance were evaluated by
      principal components analysis. The high content of cellulose and hemicellulose
      favoured lignocellulolytic enzymes production, and the phenolics content was
      negatively correlated with enzymes production and with the increase of protein by
      SSF. Furthermore, the scanning electron microscopy analysis showed the growth of
      fungi over solid wastes, the formation of conidiophores and the changes in their
      structures. CONCLUSION: The nutritional value of Mediterranean wastes was
      improved and other value-added products such as lignocellulolytic enzymes were
      produced in the same process, which could facilitate the efficient reuse of these
      wastes. (c) 2018 Society of Chemical Industry.

PMID- 29652436
TI  - Quick changes of milk fatty acids after inclusion or suppression of linseed oil
      in the diet of goats.
AB  - BACKGROUND: Lipid supplementation of ruminant diet is an excellent tool to
      improve the nutritional quality of dairy fat. The purpose of this research was to
      monitor in detail the goat milk fatty acid (FA) profile during the first 24 h
      after linseed oil (LO) supplementation or suppression in the diet. Particular
      emphasis was placed in the changes of FA with bioactive properties. Milk fat was
      analysed by gas chromatography from milkings at 0, 1, 3, 6, 12 and 24 h after
      diet shift. RESULTS: The alpha-linolenic acid levels increased 12 h after LO
      incorporation in the diet and decreased 3 h after oil suppression. Most of the
      milk 10:0 to 16:0 saturated FA decreased 24 h after LO supplementation, whereas
      oil suppression raised their levels after 6 h. Similarly, raising of mono- and
      polyunsaturated trans-FA after LO inclusion was delayed in comparison with their
      decrease after oil suppression. CONCLUSION: This study supports that ruminal
      bacteria and mammary glands would exhibit a fast responsiveness after the
      inclusion or suppression of LO in ruminant rations. Milk with an improved FA
      profile could be collected between 12 h after LO supplementation and the last
      milking before LO suppression in the diet. (c) 2018 Society of Chemical Industry.

PMID- 29652437
TI  - Effect of thermal processing towards lipid oxidation and non-enzymatic browning
      reactions of Antarctic krill (Euphausia superba) meal.
AB  - BACKGROUND: Antarctic krill is a huge source of biomass and prospective high
      quality lipid source. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA),
      nutritionally important lipid components with poor oxidative stability, were used
      as markers of oxidation during thermal processing of Antarctic krill (Euphausia
      superba) meal by evaluating the lipolysis, lipid oxidation, and non-enzymatic
      browning reactions. RESULT: Liquid chromatography-mass spectrometry of the
      phospholipids and the main oxidation products of free fatty acids and
      phosphatidylcholine (PC) was effective for evaluating the oxidation of EPA and
      DHA. During boiling, oxidation of EPA and DHA in the free fatty acid and PC
      fractions and hydrolysis of the fatty acids at the sn-2 position of the
      phospholipids were predominant. The changes in PC during drying were mainly
      attributed to the oxidation of EPA and DHA. Heat treatment increased the
      oxidation products and concentration of hydrophobic pyrrole owing to
      pyrrolization between phosphatidylethanolamine and the lipid oxidation products.
      CONCLUSION: The lipid oxidation level of Antarctic krill increased after drying,
      owing to prolonged heating under the severe conditions. (c) 2018 Society of
      Chemical Industry.

PMID- 29652438
TI  - Individualization of levodopa treatment using a microtablet dispenser and
      ambulatory accelerometry.
AB  - AIM: This 4-week open-label observational study describes the effect of
      introducing a microtablet dose dispenser and adjusting doses based on objective
      free-living motor symptom monitoring in individuals with Parkinson's disease
      (PD). METHODS: Twenty-eight outpatients with PD on stable levodopa treatment with
      dose intervals of <=4 hour had their daytime doses of levodopa replaced with
      levodopa/carbidopa microtablets, 5/1.25 mg (LC-5) delivered from a dose dispenser
      device with programmable reminders. After 2 weeks, doses were adjusted based on
      ambulatory accelerometry and clinical monitoring. RESULTS: Twenty-four
      participants completed the study per protocol. The daily levodopa dose was
      increased by 15% (112 mg, P < 0.001) from period 1 to 2, and the dose interval
      was reduced by 12% (22 minutes, P = 0.003). The treatment adherence to LC-5 was
      high in both periods. The MDS-UPDRS parts II and III, disease-specific quality of
      life (PDQ-8), wearing-off symptoms (WOQ-19), and nonmotor symptoms (NMS Quest)
      improved after dose titration, but the generic quality-of-life measure EQ-5D-5L
      did not. Blinded expert evaluation of accelerometry results demonstrated
      improvement in 60% of subjects and worsening in 25%. CONCLUSIONS: The
      introduction of a levodopa microtablet dispenser and accelerometry aided dose
      adjustments improve PD symptoms and quality of life in the short term.

PMID- 29652439
TI  - Evaluation of gaseous allyl isothiocyanate against the growth of mycotoxigenic
      fungi and mycotoxin production in corn stored for 6 months.
AB  - BACKGROUND: Brazil produces approximately 63 million tons of corn kernels
      annually, which is commonly contaminated with fungi and mycotoxins. The objective
      of this study was to evaluate the efficacy of gaseous allyl isothiocyanate (AITC)
      to inhibit the growth of Aspergillus parasiticus and Fusarium verticillioides,
      and mycotoxin production (aflatoxins B1 , B2 , G1 and G2 , fumonisins B1 and B2 )
      in corn during 180 days of storage. RESULTS: AITC at 50 uL L-1 resulted in a
      significant reduction of the fungal population (P < 0.05) after 180 days,
      decreasing 3.17 log(CFU g-1 ) and 3.9 log(CFU g-1 ) of A. parasiticus and F.
      verticillioides respectively in comparison with the control. In addition, 10 and
      50 uL L-1 treatments prevented the production of fumonisin B1 for the whole
      period. Aflatoxins were not detected in either control or treated groups.
      Residual levels of AITC in corn treated with 10 uL L-1 and 50 uL L-1 were
      detected up to 14 days and 30 days respectively. CONCLUSION: Prophylactic
      treatment with AITC reduced the fungal population and inhibited fumonisin B1
      production in stored corn, exhibiting great potential to be applied in corn silos
      to prevent fungi contamination and minimize mycotoxin levels. (c) 2018 Society of
      Chemical Industry.

PMID- 29652440
TI  - Long-term visual outcomes for treatment of submacular haemorrhage secondary to
      polypoidal choroidal vasculopathy.
AB  - IMPORTANCE: There is no consensus on the optimal management of submacular
      haemorrhage (SMH) secondary to polypoidal choroidal vasculopathy (PCV).
      BACKGROUND: To compare the long-term outcome of three treatment strategies for
      PCV with SMH. DESIGN: Retrospective case series at two tertiary hospitals.
      SAMPLES: A total of 48 consecutive eyes treated between July 2006 and March 2016.
      METHODS: Patients were grouped according to the treatment received: 22 eyes with
      intravitreal bevacizumab (IVB), 14 with a combination of IVB and pneumatic
      displacement (PD) and 12 with IVB and vitrectomy (TPPV). MAIN OUTCOME MEASURES:
      Change in best-corrected visual acuity (BCVA) at onset and up to 24 months.
      Secondary measures included demographic data, imaging data and complications.
      RESULTS: Comparing the mean BCVAs of the groups revealed significant differences
      only at month 1 (P = 0.005). Changes in the mean BCVA over time revealed no
      significance in the resulting final BCVA (P = 0.062), which was 20 out of 155
      (logMAR 0.89 +/- 0.64) for IVB monotherapy, 20 out of 174 (0.94 +/- 1.04) for
      combined IVB + PD, and 20 out of 195 (0.99 +/- 0.90) for combined IVB + TPPV
      eyes. Sustained long-term improvement of over three Snellen lines was found in
      seven (31.82%) IVB monotherapy, 10 (71.43%) combined IVB + PD, and seven (58.33%)
      combined IVB + TPPV eyes (P = 0.043). SMH recurrence was observed in two eyes
      after IVB monotherapy and one eye after combined IVB + PD (P = 0.786).
      CONCLUSIONS AND RELEVANCE: IVB monotherapy appears to be as effective as
      combination therapies for treating SMH secondary to PCV with regards to BCVA at
      24 months, and may be a cost-effective strategy for long-term management.

PMID- 29652441
TI  - Reduction of 5-hydroxymethylfurfural formation by flavan-3-ols in Maillard
      reaction models and fried potato chips.
AB  - BACKGROUND: 5-Hydroxymethylfurfural (HMF) is regarded as a thermal process
      contaminant in foods. Six flavan-3-ol fractions were isolated or semisynthesized
      from sorghum, cranberry and grape seed. Their unit compositions, interflavan
      linkages and degree of polymerization were characterized. The aim of this study
      was to investigate the effect of flavan-3-ols on the formation of HMF in chemical
      reaction models and fried potato chips. RESULTS: Results showed that all flavan-3
      ols significantly mitigated the HMF formation at concentrations of 50, 100 and
      200 ug mL-1 in the chemical model system, and the inhibition was positively
      related to dose. Using the food model, HMF content was reduced by about 50% when
      potato chips were soaked in an optimal concentration of 0.1 mg mL-1 flavan-3-ol
      solutions before frying. Based on the same mass concentration, B-type flavan-3
      ols mitigated more HMF than A-type, and oligomeric proanthocyanidins had stronger
      inhibitory activity than polymers. At suitable addition levels (0.01-0.1 mg mL-1
      ), the browning of auto-oxidized flavan-3-ols under high temperature compensated
      the anti-browning effect along with the supression of the Maillard reaction;
      therefore, the color of fried potato chips was not affected. CONCLUSION: This
      study demonstrates that flavan-3-ols could be effective additives for reducing
      HMF levels in fried potato chips without changing sensory properties. (c) 2018
      Society of Chemical Industry.

PMID- 29652442
TI  - Antioxidant hydrolyzed peptides from Manchurian walnut (Juglans mandshurica
      Maxim.) attenuate scopolamine-induced memory impairment in mice.
AB  - BACKGROUND: Walnut protein, which is obtained as a by-product of oil expression,
      has not been used efficiently. Although walnuts are beneficial for cognitive
      functioning, the potential of their protein composition in strengthening learning
      and memory functions remains unknown. In this study, the inhibition of memory
      impairment by the Manchurian walnut hydrolyzed peptide (MWHP) was evaluated.
      RESULTS: Small-molecular-weight MWHP (<3 kDa) achieved the optimal antioxidative
      activity. Therefore, MWHP (<3 kDa) was subjected to the following mice trials to
      evaluate its attenuation effect on memory impairment. In the Morris water maze
      test, MWHP shortened the total path for searching the platform, reduced the
      escape latency, and increased the dwelling distance and time in the coverage
      zone. MWHP also prolonged the latency and diminished errors in the passive
      avoidance response tests. These behavioral tests demonstrated that MWHP could
      inhibit scopolamine-induced memory impairment. MWHP improved memory by reducing
      oxidative stress, inhibiting apoptosis, regulating neurotransmitter functions,
      maintaining hippocampal CA3 pyramidal neurons, and increasing calmodulin
      dependent protein kinase II levels in brain tissues. CONCLUSION: Experimental
      results proved that MWHP exhibits potential in improving memory and should be
      used to develop novel functional food. (c) 2018 Society of Chemical Industry.

PMID- 29652443
TI  - Identification of key aromatic compounds in Congou black tea by partial least
      square regression with variable importance of projection scores and gas
      chromatography-mass spectrometry/gas chromatography-olfactometry.
AB  - BACKGROUND: Gas chromatography-olfactometry (GC-O) is the most frequently used
      method to estimate the sensory contribution of single odorant, but disregards the
      interactions between volatiles. In order to select the key volatiles responsible
      for the aroma attributes of Congou black tea (Camellia sinensis), instrumental,
      sensory and multivariate statistical approaches were applied. RESULTS: Using
      sensory analysis, nine panellists developed eight descriptors: floral, sweet,
      fruity, green, roasted, oil, spicy, and off-odour. Linalool, (E)-furan linalool
      oxide, (Z)-pyran linalool oxide, methyl salicylate, beta-myrcene, and phenylethyl
      alcohol, which were identified from the most representative samples by the GC-O
      procedure, were the essential aroma-active compounds in the formation of basic
      Congou black tea aroma. In addition, 136 volatiles were identified by gas
      chromatography-mass spectrometry (GC-MS), among which 55 compounds were
      determined as the key factors for six sensory attributes by partial least-square
      regression (PLSR) with variable importance of projection scores. CONCLUSION: Our
      results demonstrated that headspace solid-phase microextraction/GC-MS/GC-O was a
      fast approach for isolation and quantification aroma-active compounds. The PLSR
      method was also considered to be a useful tool in selecting important variables
      for sensory attributes. These two strategies, which allowed us to comprehensively
      evaluate the sensorial contribution of a single volatile from different
      perspectives, can be applied to related products for comprehensive quality
      control. (c) 2018 Society of Chemical Industry.

PMID- 29652444
TI  - Accelerated solvent extraction coupled to high-performance liquid chromatography
      tandem mass spectrometry for simultaneous determination of 11 organophosphorus
      flame retardants in aquatic products.
AB  - BACKGROUND: A new method based on accelerated solvent extraction was developed
      for the extraction and determination of 11 organophosphorus flame retardants by
      using a high-performance liquid chromatography-tandem mass spectrometry
      technique. RESULTS: After optimization of the extraction temperature (80  degrees
      C), the extraction solvent (n-hexane), the flush volume (40%) and the static
      extraction time (4 min), all 11 organophosphorus flame retardants illustrated
      good linearities (R > 0.999). The limits of detection of the method ranged from
      0.016 to 26.58 ug kg-1 in the different matrices. The recoveries were 90.4-111.2%
      with relative standard deviations 0.21-5.3% for the various aquatic products.
      CONCLUSION: The proposed method was applied successfully to detect 11
      organophosphorus flame retardants in aquatic products, including grass carp,
      ribbon fish, mud fish, common eel, shrimp and frog. (c) 2018 Society of Chemical
      Industry.

PMID- 29652445
TI  - Useful histological findings in incisional biopsies of oral squamous cell
      carcinoma.
AB  - Introduction: Oral squamous cell carcinoma (OSCC) is one of the most common head
      and neck cancers. Objective: The aim of this study was to investigate the
      histopathological features of OSCC specimens obtainedfrom incisional biopsies and
      to alert clinicians to the importance of more representative biopsies. Methods:
      Forty-eight OSCC samples were obtained from incisional biopsies and classified by
      Bryne'sscore. The following morphological features were analyzed: invasive front,
      invasiveness, apoptotic cells,atypical mitosis, giant cells, acantholysis,
      ulceration, necrosis, calcification, surface epithelium, granulationtissue,
      desmoplasia, tissue invasions, inflammatory infiltrate and tumor thickness.
      Results: Ten (21%) cases were classified as high grade malignancies and 38 (79%)
      as low grade. Apoptoticcells (n = 26), atypical mitosis (1-2/20*; n = 38), giant
      cells (n = 8), acantholysis (n = 5), necrosis (n = 5),calcification (n = 1),
      granulation tissue (n = 32), desmoplasia (n = 4), perineural invasion (n = 2),
      muscularinvasion (n = 8), invasion of salivary gland tissue (n = 3), vascular
      invasion (n = 10), and chronic inflammation(n = 33) were observed. Vascular
      invasion (p = 0.04, Pearson's chi2 test) and necrosis (p = 0.04, Pearson'schi2
      test) were significantly associated with cases of high-grade malignant tumors.
      Atypical mitosis wasassociated with a greatest tumor thickness (p = 0.04,
      Fischer's exact test). Conclusion: This study suggests that incisional biopsies
      may be useful and significant as they can showhistopathological variables that
      are important to classify oral squamous cell carcinomas into low gradeand high
      grade according to Bryne's score, which was used in this study. Thus, more
      representativebiopsies might be useful to achieve this and allow a more accurate
      planning.

PMID- 29652446
TI  - Modified Risdon approach using periangular incision in surgical treatment of
      subcondylar mandibular fractures.
AB  - Introduction: No consensus has been reached yet on the surgical approach for
      treatment of condylarfractures. Objective: The aim of this study was to present
      modified Risdon approach (without facial nerve identification)in the treatment of
      subcondylar mandibular fractures. Method: This is a retrospective study of a
      period 2005-2012. During this seven-year period, 25 condylarmandibular fractures
      in 22 men and three women (19-68 years old) were treated by modified
      Risdonapproach without identifying the facial nerve. The main inclusion criterion
      was subcondylar fractureaccording to Lindahl classification. Results: No
      additional morbidity related to postoperative complications, such as infection or
      salivary fistula,was observed in this series. Only two (8%) patients developed
      temporary weakness of the marginalbranch of the facial nerve, which resolved six
      weeks postoperatively. Each patient achieved good mouthopening postoperatively.
      Scar was camouflaged in the first cervical wrinkle. Two patients
      developedtemporomandibular joint dysfunction. No patient had postoperative
      occlusal disturbance. In all of thepatients good aesthetic result was achieved in
      a two-year follow-up. Conclusion: In comparison with techniques described in the
      literature, the main advantages of the modifiedRisdon approach are the following:
      no need for facial vessels identification; direct, fast, and safeapproach to
      mandibular angle and subcondylar region; relatively simple surgical technique and
      goodcosmetic result - due to aesthetically placed incision. This approach could
      be recommended for subcondylarfracture as a simplified and safe procedure.

PMID- 29652447
TI  - Thyroglobulin value in patients surgically treated for differentiated thyroid
      carcinoma.
AB  - Introduction: Thyroglobulin is composed glycoprotein, and it is synthesized by
      follicular cells of thethyroid gland. Treatment of differentiated thyroid
      carcinomas involves total thyroidectomy followed byradioiodine ablation of a
      potential remaining tissue. The measurement of thyroglobulin in the
      postoperativefollow-up can serve as an indicator of tumor growth or recurrence of
      the disease. Objective: The aim of this paper is to examine the value of
      thyroglobulin in patients surgically treated fordifferentiated thyroid cancer who
      had metastases in the lymph nodes of the neck, as well as in operatedon patients
      without any evident metastasis. Methods: Thyroglobulin values in the serum of 58
      patients were analyzed. Two groups were formed. Thethyroglobulin value was
      established with the use of IRMA-hTg (125I) system. Normal levels of
      thyroglobulinwere from 2 ng/ml to 65 ng/ml. For all of 58 patients, thyroglobulin
      was determined three times. Thefirst, so-called pre-ablation thyroglobulin was
      determined immediately before the application of 131Iablation dose. The second
      and the third measurements were conducted six to eight months and oneyear,
      respectively, after the application of the ablation dose respectively. Results:
      The first group consisted of 14 patients with histologically proven metastases in
      the lymphnodes of the neck, while the second group consisted of 44 patients
      without any evident metastases.The average thyroglobulin value of pre-ablation in
      the patients from the first group was 43.45 ng/ml,while in the second was 7.57
      ng/ml. Levene's test (with p = 0.00, i.e p < 0.05), demonstrated a
      statisticallysignificant difference. Furthermore, in both groups, there was
      statistically significant difference betweenpre-ablation and post-ablation
      thyroglobulin values (Student's t-test with p < 0.05). Conclusion: It can be
      concluded that the average value of thyroglobulin was significantly higher
      inpatients with lymph node metastases in the neck. We are of the opinion that the
      determination of thyroglobulin,despite individual variations, may serve as a good
      indicator to assist in monitoring of patientssurgically treated for
      differentiated thyroid cancer.

PMID- 29652449
TI  - Rising incidence of childhood type 1 diabetes in Montenegro.
AB  - Introduction: The incidence rate of childhood type1 diabetes continues to rise
      across Europe by an averageof approximately 3-4% per annum. Objective: The aim of
      this study was to examine incidence and trends of type 1 diabetes in children
      aged0-14 years in Montenegro from 1997 to 2011. Methods: This was a prospective
      study. Primary case ascertainment was from a diabetes register, anda secondary
      independent data source was from hospital notifications. Case ascertainment was
      100%complete using the capture-recapture method. Standardized incidence rates
      were calculated and trendsestimated using the Poisson regression. Results: A
      total of 298 children (157 boys and 141 girls) were diagnosed with type 1
      diabetes before 15years of age during 1997-2011. The mean age-standardized
      incidence was 15.0/100,000 persons (95%CI: 12.3-17.6) during this period,
      increasing from 11.7/100,000 in 1997 to 18.8/100,000 in 2011. The agespecific
      rates per 100,000 persons per year were 10.7, 17.2, and 18.2 at ages 0-4 years, 5
      9 years, and10-14 years, respectively. A significant linear trend in incidence (p
      = 0.002) has been observed over time,with an average annual increase of 4.2%. The
      increase in incidence was present in both genders, withthe largest relative
      increase in the 0-4 years age group for boys (11.0%; p = 0.006). Conclusion: The
      incidence of type 1 diabetes in Montenegro children continues to increase. We
      needfurther monitoring and additional research in order to explain the cause.

PMID- 29652448
TI  - Correlation between the season, temperature and atmospheric pressure with
      incidence and pathogenesis of acute appendicitis.
AB  - Introduction: There is very little literature data on the correlation between the
      seasons, temperature andatmospheric pressure, and pathogenesis of acute
      appendicitis (AA). Objective: The aim of this research is to investigate the
      association between the seasons, changes inatmospheric temperature and pressure,
      and patients' age and severity of the clinical form of AA in thecity of Nis
      Methods: This study included 395 patients diagnosed with AA, who, during the two
      year period, from July1st 2011 to June 30th 2013, were hospitalized and operated
      on at the Department of General Surgery,Clinical Center in Nis, Serbia. Results:
      The increased average daily values of barometric pressure by 1 millibar on the
      day when theevent took place was associated (p < 0.05) with the decrease of total
      risk of the occurrence of appendicitisby 2.2% (0.2-4.1%). In all observed
      patients, each increase of the mean daily temperature by 1 degrees C threedays
      before the event took place (Lag 3) was associated (p < 0.05) with the increase
      of total risk of theoccurrence of appendicitis by 1.3% (0.1-2.5%). Conclusion:
      According to the results of this research, we can conclude that patients' sex,
      age and severityof the clinical form of AA are not in connection with the
      seasons, while there are certain connectionsbetween appendicitis occurrence and
      atmospheric temperature and pressure.

PMID- 29652450
TI  - Lymphoblastic lymphomas in children - A single-center experience from Serbia.
AB  - Introduction: Intensive treatment protocols used for non-Hodgkin lymphoma in
      children lead to eventfreesurvival rates ranging from 80% to 90%. However, the
      results are less successful in developingcountries. Lymphoblastic lymphoma (LBL)
      is the second most frequent type of lymphoma in children,contributing with about
      one third to all non-Hodgkin lymphoma in childhood. Objective: The aim of the
      study was to evaluate the results of LBL treatment in University
      Children'sHospital (UCH), Belgrade. Methods: A retrospective analysis of patient
      records at UCH from 1997 to 2015 was carried out in patientsaged 0-18 years, in
      whom the diagnosis of LBL had been established. Twenty-two children wereincluded
      in the analysis. Results: Mean age at diagnosis was 10 years, with preponderance
      of male patients. All patients weretreated according to Berlin-Frankfurt-Munster
      based chemotherapy protocols. With median follow-up of91.5 months, five-year
      probability of event-free survival was 79.5% for all patients, while overall
      survivalwas 81.8%. Conclusion: Our results, although slightly inferior to those
      of leading international groups, reflect a goodtreatment outcome in our patients.

PMID- 29652451
TI  - Search for the presence of occult hepatitis C in patients with treatment-induced
      viral clearance using an ultrasensitive assay.
AB  - Introduction: Occult hepatitis C is defined by the presence of virus in the
      peripheral blood mononuclearcells (PBMCs) and/or liver cells, in the absence of
      serum viremia. Objective: To detect the persistence of occult hepatitis C in
      hemodialysis (HD) patients and patientswithout renal disease (non-renal) with
      treatment-induced clearance of hepatitis C virus (HCV) infection,using assays
      with a very low detection limit of viremia. Methods: A group of 13 HD patients
      and a group of 43 non-renal patients, with treatment-induced HCVinfection
      clearance were investigated in the study. The HD patients were treated with
      pegylated interferonalpha (PEG-IFN-alpha) only, while the non-renal patients were
      treated with a combination therapy of PEGIFN-alpha and ribavirin. Detection of a
      possible persistence of HCV RNA in the PBMCs and plasma sampleswas assessed by an
      ultrasensitive reverse transcription polymerase chain reaction (RT-PCR) assay (2
      IU/ml). Results: HCV RNA was not detected in the PBMCs and plasma samples of HD
      patients and of non-renalpatients, when assessed by the ultrasensitive RT-PCR
      assay. Conclusion: When a sensitive RT-PCR assay was applied, to determine if
      treatment induced clearance ofHCV infection had been successful, occult hepatitis
      C could not be detected by an ultrasensitive assay,neither in HD nor in non-renal
      patients.

PMID- 29652452
TI  - Factors associated with inconsistent condom use with clients among female sex
      workers in Podgorica, Montenegro.
AB  - Introduction: Female sex workers (FSWs) are a group at increased risk for human
      immunodeficiency virus(HIV) infection, and inconsistent condom use with clients
      is a known risk factor for infection in this group. Objective: The aim of the
      study was to determine factors associated with inconsistent condom use
      withclients among female sex workers in Podgorica, Montenegro. Methods: We
      conducted an HIV bio-behavioral cross-sectional study in a sample of female sex
      workersrecruited by snowball sampling. Results: A total of 142 FSWs were
      recruited. Eighty-one (57.0%) of them used condoms consistentlywith clients. HIV
      prevalence was 0.0%. In the multivariate analysis inconsistent condom use with
      clientsin the previous month was associated with clients' negative personal
      attitude [age-adjusted odds ratio(AOR) = 22.7, 95% confidence interval (CI) = 2.3
      228.0] or client's indifference (AOR = 13.0, 95% CI =1.4-118.9) towards using
      condom during sex with sexual workers, decision making by clients or bymutual
      agreement with client about using a condom (AOR = 10.2, 95% CI = 3.7-28.0), and
      early age offirst sex (AOR = 5.4, 95% CI = 1.6-18.5). Conclusion: Our results
      suggest not only the need for further promotion of condom use, informationand
      education for FSW but also the need to strengthen negotiation skills of FSWs with
      clients on regularuse of condoms, as well as the need to extend prevention
      programs to clients of FSWs.

PMID- 29652453
TI  - A case of severe type of cerebro-costo-mandibular syndrome.
AB  - Introduction: Cerebro-costo-mandibular syndrome (CCMS) is a rare disorder, with
      only 75 cases describedin the literature to date. CCMS is characterized by
      association of micrognathia and specific multiple ribdefects. It is accompanied
      by mental deficiency in considerable number of cases. Sometimes, there
      areassociated anomalies and problems, such as spine deformities, brain, heart,
      kidney or ear anomalies,feeding difficulties, delayed psychomotor development,
      and growth impairment. Depending on severityof deformities and consecutive
      respiratory insufficiency, in about 35-50% of CCMS cases, death occursduring the
      first year of life. These cases are referred to as severe types of CCMS. Case
      Outline: In this paper we present a female infant with severe type of CCMS.
      Diagnosis was establishedin the first day of life, based on micrognathia and
      findings of posterior rib-gap defects on thechest X-ray, accompanied by dyspnea.
      Progressive severe respiratory insufficiency caused by chest andair-way
      deformities and exacerbated by episodes of pneumonia, led to respiratory failure
      and death atthe age of 7.5 months. Conclusion: CCMS should be considered in every
      infant with micrognathia and rib-gap defects on chest X-ray.

PMID- 29652454
TI  - Primary reconstruction of neck defect after excision of metastatic melanoma of
      unknown primary site with regional pectoral myocutaneous flap.
AB  - Introduction: Metastatic melanoma of unknown primary (MMUP) is already a well
      described oncologicphenomenon in the literature, whereas tissue defects'
      reconstructions on the neck region always presenta challenge for the
      reconstructive surgeon. Two cases of giant metastatic, skin infiltrative neck
      tumormasses are presented. In both cases MMUP was diagnosed. Both intraoperative
      tissue defects werereconstructed using pectoralis major (PM) regional flap.
      Outline of cases: The first patient was admitted with giant tumor mass on the
      right side of the neck.The fast growing mass appeared two months prior to the
      admission. Thorough examination showed nosigns of primary tumor. Removal surgery
      was performed and the defect was reconstructed using thePM musculocutaneous flap.
      The second patient was admitted with large tumor mass on the left side ofthe
      neck. Thorough examination displayed no signs of any primary tumor. After the
      excision, the tumormass and subsequent neck dissection, reconstruction followed,
      using the pedicled PM muscle flap andpartial thickness skin transplants. There
      were no major complications in either case. The histopathologicalexaminations
      presented metastatic melanoma diagnoses. Conclusion: Clinical outcome of MMUP
      described in literature is rather variable. Different studies haveshown that
      prognosis in patients with MMUP is better than that in patients with diagnosed
      primarymelanoma with metastatic disease. Therefore, the best initial course of
      action in those cases would besurgery, according to oncological principles, if
      possible. Neck defects' reconstructions should fulfill bothfunctional and
      esthetic demands. Due to the reliability and low cost of the procedure, PM
      regional flappresents a very good and trustworthy reconstruction modality.

PMID- 29652455
TI  - Subendocardial hemorrhages in a case of extrapercardial cardiac tamponade - A
      possible mechanism of appearance.
AB  - Introduction: Subendocardial hemorrhages are grossly visible bleedings in the
      inner surface of the leftventricle, the interventricular septum, and the opposing
      papillary muscles and adjacentcolumnae carneae of the free wall of the ventricle.
      These are commonly seen in sudden profound hypotensioneither from severe blood
      loss from "shock" in the widest sense and, even more often, in combinationwith
      brain injuries. Case Outline: We present a case of a 38-year-old man, injured as
      a car driver in a frontal collision, whodied c. 45 minutes after the accident.
      The autopsy revealed severe chest trauma, including multipleright-sided direct
      rib fractures with the torn parietal pleura and right-sided pneumothorax, several
      rightlung ruptures, and a rupture of one of the lobar bronchi with
      pneumomediastinum, and prominent subcutaneous emphysema of the trunk, shoulders,
      neck and face. The patchy subendocardial hemorrhageof the left ventricle was
      observed. The cause of death is attributed to severe blunt force chest trauma.
      Conclusion: We postulate pneumomediastinum leading to extrapericardial tamponade
      as the underlyingmechanism of this subendocardial hemorrhage.

PMID- 29652456
TI  - Glomus tumor - A case report.
AB  - Introduction: Glomus tumor is a neuromyoarterial tumor. It is a rare tumor which
      accounts for about 2%of all hand tumors. The diagnosis is based on the triad of
      symptoms, clinical examination which includesthree tests, magnetic resonance
      imaging, and ultrasound imaging. The most common treatment is surgicalexcision,
      using transungual or lateral subperiosteal approach. Sclerotherapy and
      radiotherapy maybe the treatments of choice, but they are less effective. The
      recurrence rate is high - from 5% to 50%. Case Outline: We diagnosed a glomus
      tumor of 1 cm in diameter in the distal phalanx of the fourth fingerof the right
      hand in a 30-year-old woman. She had been visiting different physicians for more
      thantwo years and had been variously diagnosed. We performed a biopsy of the
      tumor, which was bleedingprofusely during the procedure. Upon biopsy results, the
      tumor was excised with transungual approach.Two and a half months after the
      procedure the patient was feeling well. Conclusion: There should be higher
      awareness of this tumor in order to diagnose it more easily and treatit
      accordingly, and thus alleviate the severe pain which the tumor causes. When it
      is considered as thepossible cause of the lesion, the diagnosing is easier and
      treatment is immediate.

PMID- 29652457
TI  - Allogeneic fetal stem cell transplantation to child with psychomotor retardation 
      A case report.
AB  - Introduction: The consequences of autologous and allogeneic stem cell
      transplantation (stem cells ofhematopoiesis), applied in adults and children
      suffering from leukemia or some other malignant disease,are well-known and
      sufficiently recognizable in pediatric clinical practice regardless of the
      indicationfor the treatment. However, the efficacy of fetal stem cell
      transplantation is unrecognizable when theindications are psychomotor retardation
      and epilepsy. Case Outline: With the exception of neurological psychiatric
      problems, a boy aged 9.5 years was in goodgeneral health before transplantation
      with allogeneic fetal stem cells. The main aim of allogeneic fetalstem cell
      transplantation was treatment of psychomotor retardation and epilepsy. After 13
      months oftreatment, he was admitted to hospital in a very serious, life
      threatening condition due to sepsis andsevere pleuropneumonia. The humoral
      immunity in the boy was adequate, unlike cellular immunity.The immune imbalance
      in terms of predominance of T-suppressor lymphocytes contributes to delayedand
      late development of sepsis and severe pleuropneumonia. The boy still shows the
      same severity ofpsychomotor retardation, dyslalia, epilepsy, strabismus and
      amblyopia. Conclusion: Implementation of fetal stem cell therapy for unconfirmed
      indications abuses the therapeuticapproach, harms patients, misleads parents, and
      brings financial harm to the healthcare system of anycountry, including Serbia.

PMID- 29652458
TI  - Capture the fracture - Use of bone turnover markers in clinical practice.
AB  - Bone is a living tissue, metabolically very active, with the level of turnover of
      about 10% per year. Boneremodeling is a well-balanced process of bone resorption,
      induced by osteoclasts and bone formationmaintainedosteoblasts. Loss of bone
      remodeling balance, with increased bone resorption, leads toosteoporosis. Bone
      turnover markers are classified as markers of bone formation and of bone
      resorption.During the growth and development of skeleton, bone turnover markers
      show higher levels of activitythan in the adult period. The increase in
      biochemical markers peaks again in the postmenopausalperiod, indicating
      accelerated bone remodeling. Bone mineral density is an important predictor of
      anosteoporotic fracture. Timely assessment of risk factors of osteoporosis and
      bone markers can detectsubjects with accelerated bone remodeling and
      osteoporosis. This may introduce adequate therapyand prevent fracture.

PMID- 29652459
TI  - Can we always take analysis of complete blood count by automated blood cell
      analyzer as absolutely correct?

PMID- 29652460
TI  - Anterior and middle superior alveolar block is efficient for maxillary premolar
      teeth extractions regardless of the injection system or anesthetic with
      adrenaline used.
AB  - Introduction: The anterior and middle superior alveolar nerve block was claimed
      to be unpredictablyefficient for clinical application. Objective: The aim of this
      report was to establish the efficacy of the anterior and middle superior
      alveolarnerve block, applied with a computer-controlled injection system or a
      conventional syringe, for upperpremolars extraction. Methods: Sixty healthy
      adults were divided into two groups regarding the device used as follows: the
      firstgroup was injected by a computer-controlled injection system, and the second
      group by a conventionalsyringe. Pain ratings were obtained via a visual analog
      scale (VAS) and a verbal rating scale (VRS). Results: Anterior and middle
      superior alveolar injection enabled a painless extraction in all
      patients,regardless of the local anesthetic or injection system used. It was
      slightly less painful when administeredby a computer-controlled injection system,
      but insignificantly when evaluated by VRS. Conclusion: The anterior and middle
      superior alveolar nerve block may be recommended if maxillarypermanent premolars
      have to be extracted.

PMID- 29652461
TI  - Prosthetic treatment after teeth extractions in patients with type 2 diabetes
      mellitus.
AB  - Introduction: Good and well balanced diet provided by adequate mastication is
      part of therapy in patientswith type 2 diabetes mellitus (DM). The critical
      period presents the time immediately after teeth extractions;hence, immediate
      denture is a rational therapeutical choice for diabetic patients. The presenceof
      immediate denture and its compression might compromise wound healing process,
      affect chewingability, food intake and consequently blood glucose level in type 2
      DM patients. Objective: The objective of this study was to compare socket opening
      diameters (SOD), chewing ability,changes in blood glucose level and food intake
      in type 2 DM patients with and without maxillary immediatecomplete denture (MICD)
      during a three-week wound healing period. Methods: The study comprised 78 type 2
      DM partially removable denture wearers (42 candidates for teethextractions and 36
      candidates for teeth extractions and insertion of MICDs). During the three-week
      periodparticipants were followed for SOD, chewing ability and changes in blood
      glucose level and food intake. Results: Patients with MICD showed significantly
      lower reduction of SOD (seventh, 14th, 21st day) andhigher chewing ability
      (seventh, 14th, 21st day) in comparison to patients without an MICD.
      Significantlylower number of patients with an MICD had changes in blood glucose
      level and food intake. Conclusion: Maxillary immediate complete denture presents
      a good therapeutic choice for type 2 DMpatients, as it provides possibility of
      adequate mastication after teeth extractions and maintenance ofnutritional status
      and blood glucose level.

PMID- 29652462
TI  - Efficiency of photodynamic therapy in the treatment of peri-implantitis - A three
      month randomized controlled clinical trial.
AB  - Introduction: Peri-implantitis is an inflammatory lesion of peri-implant tissues.
      Eradication of the causativebacteria and decontamination of the implant surface
      is essential in achieving predictable and stabileclinical results. Photodynamic
      therapy (PDT) is non-invasive adjuvant therapeutic method to surgery inthe
      treatment of bacterial infection. Objective: The aim of this study was to
      evaluate early clinical and microbiological outcomes of periimplantitisafter
      surgical therapy with adjuvant PDT. Methods: Fifty-two diagnosed peri-implantitis
      sites were divided into two groups. PDT was used fordecontamination of implant
      surface in the study group; in the control group, chlorhexidine gel (CHX)followed
      by saline irrigation was applied. Several clinical parameters were recorded
      before the treatment(baseline values) and three months after surgical treatment.
      Samples for microbiological identificationwere collected before therapy, during
      the surgical therapy (before and after decontamination of implantsurface), and
      three months thereafter, and analyzed with identification systems using
      biochemicalanalysis. Results: The use of PDT resulted in significant decrease of
      bleeding on probing in comparison to CHX(p < 0.001). It showed significant
      decontamination of implant surfaces with complete elimination ofanaerobic
      bacteria immediately after surgical procedure and three months later. Conclusion:
      The results indicate that PDT can be used as an adjuvant therapy to surgery for
      decontaminationof implant surface and surrounding peri-implant tissues within the
      treatment of peri-implantitis.

PMID- 29652463
TI  - Location of out-of-hospital cardiac arrest as a determinant in the survival of
      patients.
AB  - Introduction: Cardiac arrest (CA) is defined as a sudden cessation of normal
      circulation of blood due tofailure of the heart to contract effectively during
      systole. Objective: The aim of this study was to determine the difference in
      outcome among patients, dependingon the location of out-of-hospital CA; to
      determine the influence of observed determinants on thesurvival rate. Methods:
      Observational and retrospective study was conducted in the Institute for
      Emergency MedicalService Novi Sad (IEMS NS). It included patients who underwent
      cardiopulmonary resuscitation (CPR) bymedical ambulance squads. Patients were
      divided into three groups, based on the location of CA: privateplace, public
      place, and medical institution. Results: CA occurred in private places in 151
      cases (76.26%). The shortest duration of a phone call withthe dispatcher and
      Reaction Time I was in the group of patients with CA in a public place (59.1 +/-
      36.4seconds and 137.1 +/- 89.8 seconds, respectively). CA was recognized in more
      than 80% of cases, butCPR was initiated in only 9.09% of patients in private
      places and in 19.35% of patients in public places.Though they initially presented
      with shockable rhythm in 57.14% of cases in public places, this grouphas the
      worst immediate outcome (11.43%), in contrast to the patients with CA in medical
      institutions(58.33%). Factors determining the survival of patients with CA were
      CPR attempted immediately aftercollapse, initial rhythm and eyewitnesses of CA.
      Conclusion: In order to improve survival of patients with out-of-hospital CA,
      both education of laymenand introduction of standard questioning protocol in the
      IEMS Call Centre are necessary.

PMID- 29652464
TI  - Risk factors for healthcare-acquired urinary tract infections caused by multi
      drug resistant microorganisms.
AB  - Introduction: Healthcare-acquired urinary tract infections (HAUTI) make up to 40%
      of all healthcareacquiredinfections and contribute significantly to hospital
      morbidity, mortality, and overall cost oftreatment. Objective: The aim of our
      study was to investigate possible risk factors for development of HAUTI causedby
      multi-drug resistant pathogens. Methods: The prospective case-control study in a
      large tertiary-care hospital was conducted during afive-year period. The cases
      were patients with HAUTI caused by multi-drug resistant (MDR) pathogens,and the
      controls were patients with HAUTI caused by non-MDR pathogens. Results: There
      were 562 (62.6%) patients with MDR isolates and 336 (37.4%) patients with non-MDR
      isolatesin the study. There were four significant predictors of HAUTI caused by
      MDR pathogens: hospitalizationbefore insertion of urinary catheter for more than
      eight days (ORadjusted = 2.763; 95% CI = 1.352-5.647;p = 0.005), hospitalization
      for more than 15 days (ORadjusted = 2.144; 95% CI = 1.547-2.970; p <
      0.001),previous stay in another department (intensive care units, other wards or
      hospitals) (ORadjusted = 2.147; 95%CI = 1.585-2.908; p < 0.001), and cancer of
      various localizations (ORadjusted = 2.313; 95% CI = 1.255-4.262;p = 0.007).
      Conclusion: Early removal of urinary catheter and reduction of time spent in a
      hospital or in an ICU couldcontribute to a decrease in the rate of HAUTI caused
      by MDR pathogens.

PMID- 29652465
TI  - The effect of combination therapy of insulin glargine, metformin, and sitagliptin
      on insulin secretion, insulin resistance, and metabolic parameters in obese
      subjects with type 2 diabetes.
AB  - Introduction: A combination of drugs is required for treatment of obese subjects
      with diabetes, due tomultiple pathogenic mechanisms implicated in the development
      of both diabetes and obesity. Objective: Assessment of the effect of sitagliptin
      added to insulin glargine and metformin, in obesesubjects with type 2 diabetes.
      Methods: A total of 23 obese subjects on metformin and insulin glargine
      participated in the study. Titrationof insulin glargine during a one-month period
      preceded the addition of 100 mg of sitagliptin daily.Body mass index, waist
      circumference, fasting, and prandial glucose were measured monthly, lipids
      andhemoglobin A1c (HbA1c) every three months, insulin, c-peptide and glucagon at
      the start and after sixmonths of treatment. Homeostatic models for insulin
      secretion (HOMA B) and insulin resistance (HOMAIR) were calculated. Results:
      Participants were 58.65 +/- 7.62 years of age with a body mass index of 35.06 +/-
      5.15 kg/m2, waistcircumference of 115.04 +/- 15.5 cm, and the duration of
      diabetes of 4.11 +/- 2.57 years. With the titrationof insulin glargine, target
      fasting glucose levels were not achieved. Waist circumference and bodymass index
      decreased during three months of sitagliptin treatment, thereafter remaining
      stable. HbA1cdecreased significantly after three and six months of therapy. C
      peptide increased significantly, whileglucagon level fell. HOMA indexes were
      unchanged. Conclusion: Sitagliptin can improve diabetes control and induce modest
      weight loss in obese subjectspoorly controlled on insulin glargine and metformin.
      Titration of insulin glargine to optimal fasting glucosevalues is a prerequisite
      of success of this combination therapy.

PMID- 29652466
TI  - Treatment of stump complications after above-knee amputation using negative
      pressure wound therapy.
AB  - Introduction: The stump wound complications after above-knee amputation lead to
      other problems,such as prolonged rehabilitation, delayed prosthetic restoration,
      the increase in total treatment costand high mortality rates. Objective: To
      evaluate the safety and outcomes of negative-pressure wound therapy (NPWT)
      usingVacuum-Assisted Closure (VAC(r)) therapy in patients with stump complication
      after above-knee amputation(AKA). Methods: From January 2011 to July 2014, AKA
      was performed in 137 patients at the University CardiovascularClinic. Nineteen
      (12.4%) of these patients (mean age 69.3 +/- 9.2 years) were treated with
      NPWT.The following variables were recorded: wound healing and hospitalization
      time, rate of NPWT treatmentfailure, and mortality. Results: AKA was performed in
      17 (89.5%) patients after the vascular or endovascular procedures hadbeen
      exhausted, while urgent AKA was performed in two (10.5%) patients due to
      uncontrolled infection.The time before NPWT application was 3.1 +/- 1.9 days and
      the duration of the NPWT use ranged from 15to 54 days (mean 27.95 +/- 12.1 days).
      During NPWT treatment, operative debridement was performed in12 patients. All the
      patients were kept on culture-directed intravenous antibiotics. The average
      hospitallength of stay was 34.7 days (range 21-77 days). There were four (20.9%)
      failures during the treatmentwhich required secondary amputation. During the
      treatment, one (5.3%) patient died due to multi-organfailure after 27 days.
      Conclusions: The use of NPWT therapy in the treatment of AKA stump complication
      is a safe and effectiveprocedure associated with low risk and positive outcome in
      terms of wound healing time and furthercomplications.

PMID- 29652467
TI  - Three-Dimensional Porous Nickel Frameworks Anchored with Cross-Linked Ni(OH)2
      Nanosheets as a Highly Sensitive Nonenzymatic Glucose Sensor.
AB  - A facile and scalable in situ microelectrolysis nanofabrication technique is
      developed for preparing cross-linked Ni(OH)2 nanosheets on a novel three
      dimensional porous nickel template (Ni(OH)2@3DPN). For the constructed template,
      the porogen of NaCl particles not only induces a self-limiting surficial hot
      corrosion to claim the "start engine stop" mechanism but also serves as the
      primary battery electrolyte to greatly accelerate the growth of Ni(OH)2. As far
      as we know, the microelectrolysis nanofabrication is superior to the other
      reported Ni(OH)2 synthesis methods due to the mild condition (60  degrees C, 6 h,
      NaCl solution, ambient environment) and without any post-treatment. The
      integrated Ni(OH)2@3DPN electrode with a highly suitable microstructure and a
      porous architecture implies a potential application in electrochemistry. As a
      proof-of-concept demonstration, the electrode was employed for nonenzymatic
      glucose sensing, which exhibits an outstanding sensitivity of 2761.6 MUA mM-1 cm
      2 ranging from 0.46 to 2100 MUM, a fast response, and a low detection limit. The
      microelectrolysis nanofabrication is a one-step, binder-free, entirely green, and
      therefore it has a distinct advantage to improve clean production and reduce
      energy consumption.

PMID- 29652468
TI  - Changes in Cementation of Reef Building Oysters Transitioning from Larvae to
      Adults.
AB  - Oysters construct extensive reef communities, providing food, protection from
      storms, and healthy coastlines. We still do not have a clear picture of how these
      animals attach to surfaces. Efforts described herein provide the first
      examination of adhesion at the transition from free swimming larvae to initial
      substrate attachment, through metamorphosis, and on to adulthood. Two different
      bonding systems were found to coexist. Larvae use an organic, hydrated glue that
      persists while the animal progresses into the juvenile phase, at which point a
      very different adhesive emerges. Juveniles bond with an organic-inorganic
      composite system, positioning the organic component for maximum adhesion by
      residing between the animal and substrate. Beyond understanding our marine
      environment, these insights may aid efforts in aquaculture, reef restoration, and
      adhesive design.

PMID- 29652469
TI  - Coordination Polymer-Derived Multishelled Mixed Ni-Co Oxide Microspheres for
      Robust and Selective Detection of Xylene.
AB  - Multishell, stable, porous metal-oxide microspheres (Ni-Co oxides, Co3O4 and NiO)
      have been synthesized through the amorphous coordination polymer-based self
      templated method. Both oxides of Ni and Co show poor selectivity to xylene, but
      the composite phase has substantial selectivity (e.g., Sxylene/ Sethanol = 2.69)
      and remarkable sensitivity (11.5-5 ppm xylene at 255  degrees C). The short
      response and recovery times (6 and 9 s), excellent humidity-resistance
      performance (with coefficient of variation = 11.4%), good cyclability, and long
      term stability (sensitivity attenuation of ~9.5% after 30 days and stable
      sensitivity thereafter) all show that this composite is a competitive solution to
      the problem of xylene sensing. The sensing performances are evidently due to the
      high specific surface area and the nano-heterostructure in the composite phase.

PMID- 29652470
TI  - Fabrication and Characterization of Hybrid Organic-Inorganic Electron Extraction
      Layers for Polymer Solar Cells toward Improved Processing Robustness and Air
      Stability.
AB  - Organic-inorganic hybrid materials composed of bismuth and diaminopyridine are
      studied as novel materials for electron extraction layers in polymer solar cells
      using regular device structures. The hybrid materials are solution processed on
      top of two different low band gap polymers (PTB7 or PTB7-Th) as donor materials
      mixed with fullerene PC70BM as the acceptor. The intercalation of the hybrid
      layer between the photoactive layer and the aluminum cathode leads to solar cells
      with a power conversion efficiency of 7.8% because of significant improvements in
      all photovoltaic parameters, that is, short-circuit current density, fill factor,
      and open-circuit voltage, similar to the reference devices using ZnO as the
      interfacial layer. However when using thick layers of such hybrid materials for
      electron extraction, only small losses in photocurrent density are observed in
      contrast to the reference material ZnO of pronounced losses because of optical
      spacer effects. Importantly, these hybrid electron extraction layers also
      strongly improve the device stability in air compared with solar cells processed
      with ZnO interlayers. Both results underline the high potential of this new class
      of hybrid materials as electron extraction materials toward robust processing of
      air stable organic solar cells.

PMID- 29652471
TI  - Influence of the Chalcogen Element on the Filament Stability in
      CuIn(Te,Se,S)2/Al2O3 Filamentary Switching Devices.
AB  - In this paper, we report on the use of CuInX2 (X = Te, Se, S) as a cation supply
      layer in filamentary switching applications. Being used as absorber layers in
      solar cells, we take advantage of the reported Cu ionic conductivity of these
      materials to investigate the effect of the chalcogen element on filament
      stability. In situ X-ray diffraction showed material stability attractive for
      back-end-of-line in semiconductor industry. When integrated in 580 MUm diameter
      memory cells, more volatile switching was found at low compliance current using
      CuInS2 and CuInSe2 compared to CuInTe2, which is ascribed to the natural tendency
      for Cu to diffuse back from the switching layer to the cation supply layer
      because of the larger difference in electrochemical potential using Se or S. Low
      current and scaled behavior was also confirmed using conductive atomic force
      microscopy. Hence, by varying the chalcogen element, a method is presented to
      modulate the filament stability.

PMID- 29652472
TI  - New Class of Hybrid Materials for Detection, Capture, and "On-Demand" Release of
      Carbon Monoxide.
AB  - Carbon monoxide (CO) is both a substance hazardous to health and a side product
      of a number of industrial processes, such as methanol steam reforming and large
      scale oxidation reactions. The separation of CO from nitrogen (N2) in industrial
      processes is considered to be difficult because of the similarities of their
      electronic structures, sizes, and physicochemical properties (e.g., boiling
      points). Carbon monoxide is also a major poison in fuel cells because of its
      adsorption onto the active sites of the catalysts. It is therefore of the utmost
      economic importance to discover new materials that enable effective CO capture
      and release under mild conditions. However, methods to specifically absorb and
      easily release CO in the presence of contaminants, such as water, nitrogen,
      carbon dioxide, and oxygen, at ambient temperature are not available. Here, we
      report the simple and versatile fabrication of a new class of hybrid materials
      that allows capture and release of carbon monoxide under mild conditions. We
      found that carborane-containing metal complexes encapsulated in networks made of
      poly(dimethylsiloxane) react with CO, even when immersed in water, leading to
      dramatic color and infrared signature changes. Furthermore, we found that the CO
      can be easily released from the materials by simply dipping the networks into an
      organic solvent for less than 1 min, at ambient temperature and pressure, which
      not only offers a straightforward recycling method, but also a new method for the
      "on-demand" release of carbon monoxide. We illustrated the utilization of the on
      demand release of CO from the networks by carrying out a carbonylation reaction
      on an electron-deficient metal complex that led to the formation of the CO
      adduct, with concomitant recycling of the gel. We anticipate that our sponge-like
      materials and scalable methodology will open up new avenues for the storage,
      transport, and controlled release of CO, the silent killer and a major industrial
      poison.

PMID- 29652473
TI  - Smart Photosensitizer: Tumor-Triggered Oncotherapy by Self-Assembly Photodynamic
      Nanodots.
AB  - Clinical photosensitizers suffer from the disadvantages of fast photobleaching
      and high systemic toxicities because of the off-target photodynamic effects. To
      address these problems, we report a self-assembled pentalysine-phthalocyanine
      assembly nanodots (PPAN) fabricated by an amphipathic photosensitizer-peptide
      conjugate. We triggered the photodynamic therapy effects of photosensitizers by
      precisely controlling the assembly and disintegration of the nanodots. In
      physiological aqueous conditions, PPAN exhibited a size-tunable spherical
      conformation with a highly positive shell of the polypeptides and a hydrophobic
      core of the pi-stacking Pc moieties. The assembly conformation suppressed the
      fluorescence and the reactive oxygen species generation of the monomeric
      photosensitizer molecules (mono-Pc) and thus declined the photobleaching and off
      target photodynamic effects. However, tumor cells disintegrated PPAN and released
      the mono-Pc molecules, which exhibited fluorescence for detection and the
      photodynamic effects for the elimination of the tumor tissues. The molecular
      dynamics simulations revealed the various assembly configurations of PPAN and
      illustrated the assembly mechanism. At the cellular level, PPAN exhibited a
      remarkable phototoxicity to breast cancer cells with the IC50 values in a low
      nanomolar range. By using the subcutaneous and orthotopic breast cancer animal
      models, we also demonstrated the excellent antitumor efficacies of PPAN in vivo.

PMID- 29652474
TI  - Polydopamine Induced in-Situ Formation of Metallic Nanoparticles in Confined
      Microchannels of Porous Membrane as Flexible Catalytic Reactor.
AB  - Oxidant-regulated polymerization of dopamine was exploited, for the first time,
      for effective surface engineering of the well-defined cylindrical pores of
      nuclear track-etched membranes (NTEMs) to develop novel catalytic membrane
      reactor. First, in the presence of a strong oxidant, controlled synthesis of
      polydopamine (PDA) with tunable particle size was achieved, allowing a
      homogeneous deposition to the confined pore channels of NTEMs. The PDA interfaces
      rich in catechol and amine groups provided enhanced hydrophilicity to promote
      mass transport across the membrane and abundant nucleation sites for formation
      and stabilization of metallic nanoparticles (NPs). In-situ reductive growth of
      multiple metallic NPs, including Pd, Ag, and Au, was then achieved inside the
      cylindrical pores of NTEMs. Using the functionalized membrane as a catalytic
      reactor, efficient reduction of 4-nitrophenol (4-NP) was demonstrated in a flow
      through mode. Moreover, after dissolution removal of the NTEMs, self-sustained
      one-dimensional (1D) PDA/M (M = Pd, Ag, or Au) hybrid nanotubes (NTs), with
      determined aspect ratio and a length reaching up to 10 MUm, were obtained for
      catalysis of 4-NP in a batch reaction mode. This study established a facile and
      versatile method, by rational tuning of the polymerization behavior of dopamine,
      for effective modification of confined microscale/nanoscale cavities with
      different surface characteristics. The integration of PDA chemistry with NTEMs
      would provide more opportunities for development of novel catalytic membrane
      reactors as well as for the tailored synthesis of functional 1D nanotubes for
      broadened applications.

PMID- 29652475
TI  - Ultrastable Quantum Dot Composite Films under Severe Environments.
AB  - Semiconductor quantum dots (QDs) have attracted extensive attention because of
      their remarkable optical and electrical characteristics. However, the practical
      application of QDs and further the QD composite films have greatly been hindered
      mainly owing to their essential drawbacks of extreme unstability under oxygen and
      water environments. Herein, one simple method has been employed to enhance
      enormously the stability of Cd xZn1- xSe yS1- y QD composite films by a
      combination of Cd xZn1- xSe yS1- y QDs and poly(vinylidene) fluoride (PVDF),
      which is characteristic of closely arranged molecular chains and strong hydrogen
      bonds. There are many particular advantages in using QD/PVDF composite films such
      as easy processing, low cost, large-area fabrication, and especially extreme
      stability even in the boiling water for more than 240 min. By employing
      K2SiF6:Mn4+ as a red phosphor, a prototype white light-emitting diode (WLED) with
      color coordinates of (0.3307, 0.3387), Tc of 5568 K, and color gamut
      112.1NTSC(1931)% at 20 mA has been fabricated, and there is little variation
      under different excitation currents, indicating that the QD/PVDF composite films
      fabricated by this simple blade-coating process make them ideal candidates for
      liquid-crystal display backlight utilization via assembling a WLED on a large
      scale owing to its ultrahigh stability under severe environments.

PMID- 29652476
TI  - Super Tough, Ultrastretchable Hydrogel with Multistimuli Responsiveness.
AB  - The research of hydrogels has been increasingly focused on designing an effective
      energy dissipation structure in recent years. Here, we report a kind of novel
      supramolecular cross-linker, which was formed by self-assembling amphiphilic
      block copolymers with guest groups at the end and vinyl-functionalized
      cyclodextrin (CD) through host-guest interaction. These cross-linkers could
      dissipate energy effectively since they combined multiple sacrificial mechanisms
      across multiscales through physical interactions. The resulted hydrogel shows
      distinguishing mechanical properties (fracture toughness of 2.68 +/- 0.69 MJ/m3,
      tension strength of up to 475 kPa, uniaxial stretch over 2100%), remarkable
      fatigue resistance, and thermal- and light-responsive behaviors.

PMID- 29652477
TI  - Targeted Nanoparticles for Selective Marking of Neuromuscular Junctions and ex
      Vivo Monitoring of Endogenous Acetylcholine Hydrolysis.
AB  - The present work for the first time introduces nanosensors for luminescent
      monitoring of acetylcholinesterase (AChE)-catalyzed hydrolysis of endogenous
      acetylcholine (ACh) released in neuromuscular junctions of isolated muscles. The
      sensing function results from the quenching of Tb(III)-centered luminescence due
      to proton-induced degradation of luminescent Tb(III) complexes doped into silica
      nanoparticles (SNs, 23 nm), when acetic acid is produced from the enzymatic
      hydrolysis of ACh. The targeting of the silica nanoparticles by alpha
      bungarotoxin was used for selective staining of the synaptic space in the
      isolated muscles by the nanosensors. The targeting procedure was optimized for
      the high sensing sensitivity. The measuring of the Tb(III)-centered luminescence
      intensity of the targeted SNs by fluorescent microscopy enables us to sense a
      release of endogenous ACh in neuromuscular junctions of the isolated muscles
      under their stimulation by a high-frequency train (20 Hz, for 3 min). The ability
      of the targeted SNs to sense an inhibiting effect of paraoxon on enzymatic
      activity of AChE in ex vivo conditions provides a way of mimicking external
      stimuli effects on enzymatic processes in the isolated muscles.

PMID- 29652478
TI  - Isothermal Self-Assembly of Spermidine-DNA Nanostructure Complex as a Functional
      Platform for Cancer Therapy.
AB  - Programmable DNA nanostructure self-assembly offers great potentials in
      nanomedicine, drug delivery, biosensing, and bioimaging. However, due to the
      intrinsically negatively charged DNA backbones, the instability of DNA
      nanostructures in physiological settings poses serious challenges to their
      practical applications. To overcome this challenge, a strategy that combines the
      magnesium-free DNA self-assembly and functionalization is proposed in this study.
      We hypothesize that naturally abundant spermidine may not only mediate the self
      assembly of DNA nanostructures, but also shield them from harsh physiological
      environments. As a proof of concept, a DNA nanoprism is designed and synthesized
      successfully through spermidine. It is found that spermidine can mediate the
      isothermal self-assembly of DNA nanoprisms. Compared to conventional Mg2+
      assembled DNA nanostructures, the spermidine-DNA nanoprism complex shows higher
      thermal stability and better enzymatic resistance than Mg2+-assembled DNA
      nanoprisms, and more importantly, it has a much higher cellular uptake efficacy
      in multiple cancerous cell lines. The internalization mechanism is identified as
      clathrin-mediated endocytosis. To demonstrate the suitability of this new
      nanomaterial for biomedical applications, an mTOR siRNA, after being conjugated
      into the complex, is efficiently delivered into cancer cells and shows excellent
      gene knockdown efficacy and anticancer capability. These findings indicate that
      the spermidine-DNA complex nanomaterials might be a promising platform for
      biomedical applications in the future.

PMID- 29652479
TI  - A Thermal-, Water-, and Near-Infrared Light-Induced Shape Memory Composite Based
      on Polyvinyl Alcohol and Polyaniline Fibers.
AB  - A multiresponsive shape memory composite was prepared by incorporating
      polyaniline (PAn) fibers into polyvinyl alcohol (PVA), where in situ
      polymerization assisted by surfactant was used to homogeneously disperse PAn
      fibers in a PVA matrix. The PAn fibers not only increased physical cross-linking
      points in the system but also served as photothermal conversion reagents,
      resulting in excellent water-, thermal-, and near-infrared (NIR) light-induced
      shape memory properties of the composites, where their light-induced shape
      recovery ratio and speed could be enhanced via the increase of PAn loading
      percentage and light power density. Moreover, the composites possessed high
      mechanical properties with tensile strength over 83 MPa. On the basis of these
      dramatic mechanical properties and shape memory properties, the composites could
      show high recovery stress over 6.0 MPa, which increased with the increase of
      temperature and PAn loading percentage. This presented composite could be a great
      candidate as actuator element for various applications.

PMID- 29652480
TI  - Single-Crystal Antimonene Films Prepared by Molecular Beam Epitaxy: Selective
      Growth and Contact Resistance Reduction of the 2D Material Heterostructure.
AB  - Single-crystal antimonene flakes are observed on sapphire substrates after the
      postgrowth annealing procedure of amorphous antimony (Sb) droplets prepared by
      using molecular beam epitaxy at room temperature. The large wetting angles of the
      antimonene flakes to the sapphire substrate suggest that an alternate substrate
      should be adopted to obtain a continuous antimonene film. By using a bilayer
      MoS2/sapphire sample as the new substrate, a continuous and single-crystal
      antimonene film is obtained at a low growth temperature of 200  degrees C. The
      results are consistent with the theoretical prediction of the lower interface
      energy between antimonene and MoS2. The different interface energies of
      antimonene between sapphire and MoS2 surfaces lead to the selective growth of
      antimonene only atop MoS2 surfaces on a prepatterned MoS2/sapphire substrate.
      With similar sheet resistance to graphene, it is possible to use antimonene as
      the contact metal of 2D material devices. Compared with Au/Ti electrodes, a
      specific contact resistance reduction up to 3 orders of magnitude is observed by
      using the multilayer antimonene as the contact metal to MoS2. The lower contact
      resistance, the lower growth temperature, and the preferential growth to other 2D
      materials have made antimonene a promising candidate as the contact metal for 2D
      material devices.

PMID- 29652481
TI  - Amplified Sensitivity of Nitrogen-Vacancy Spins in Nanodiamonds Using All-Optical
      Charge Readout.
AB  - Nanodiamonds containing nitrogen-vacancy (NV) centers offer a versatile platform
      for sensing applications spanning from nanomagnetism to in vivo monitoring of
      cellular processes. In many cases, however, weak optical signals and poor
      contrast demand long acquisition times that prevent the measurement of
      environmental dynamics. Here, we demonstrate the ability to perform fast, high
      contrast optical measurements of charge distributions in ensembles of NV centers
      in nanodiamonds and use the technique to improve the spin-readout signal-to-noise
      ratio through spin-to-charge conversion. A study of 38 nanodiamonds with sizes
      ranging between 20 and 70 nm, each hosting a small ensemble of NV centers,
      uncovers complex, multiple time scale dynamics due to radiative and nonradiative
      ionization and recombination processes. Nonetheless, the NV-containing
      nanodiamonds universally exhibit charge-dependent photoluminescence contrasts and
      the potential for enhanced spin readout using spin-to-charge conversion. We use
      the technique to speed up a T1 relaxometry measurement by a factor of 5.

PMID- 29652482
TI  - Tunable Free-Standing Core-Shell CNT@MoSe2 Anode for Lithium Storage.
AB  - Heterogeneous nanostructuring of MoSe2 over a carbon nanotube (CNT) sponge as a
      free-standing electrode not only brings higher performance but also eliminates
      the need for dead elements such as a binder, conductive carbon, and supportive
      current collectors. Further, the porous CNT sponge can be easily compacted via an
      intense densification of the active material MoSe2 to produce an electrode with a
      high mass loading for a significantly improved areal capacity. In this work, we
      present a tunable coating of MoSe2 on a CNT sponge to fabricate a core-shell
      MoSe2@CNT anode. The three-dimensional nanotubular sponge is synthesized via a
      solvothermal process, followed by thermal annealing to improve crystallization.
      Structural and morphological studies revealed that MoSe2 grew as a layered
      structure ( d = 0.66 nm), where numbers of layers can be controlled to yield
      optimized results for Li+ storage. We showed that the 10-layer core-shell
      CNT@MoSe2 hybrid sponge delivered a discharge capacity of 820.5 mAh g-1 after 100
      cycles at 100 mA g-1 with a high cyclic stability and rate capability. Further,
      an ex situ structural and morphological analysis revealed that ionic storage
      causes a phase change in MoSe2 from a crystalline to a partial amorphous state
      for a continuous increase in the capacity with extended cycling. We believe that
      the strategy developed here will assist users to tune the electrode materials for
      future energy-storage devices, especially how the materials are changing with the
      passage of time and their effects on the device performance.

PMID- 29652483
TI  - Molecular Bases of PDE4D Inhibition by Memory-Enhancing GEBR Library Compounds.
AB  - Selected members of the large rolipram-related GEBR family of type 4
      phosphodiesterase (PDE4) inhibitors have been shown to facilitate long-term
      potentiation and to improve memory functions without causing emetic-like behavior
      in rodents. Despite their micromolar-range binding affinities and their promising
      pharmacological and toxicological profiles, few if any structure-activity
      relationship studies have been performed to elucidate the molecular bases of
      their action. Here, we report the crystal structure of a number of GEBR library
      compounds in complex with the catalytic domain of PDE4D as well as their
      inhibitory profiles for both the long PDE4D3 isoform and the catalytic domain
      alone. Furthermore, we assessed the stability of the observed ligand
      conformations in the context of the intact enzyme using molecular dynamics
      simulations. The longer and more flexible ligands appear to be capable of forming
      contacts with the regulatory portion of the enzyme, thus possibly allowing some
      degree of selectivity between the different PDE4 isoforms.

PMID- 29652484
TI  - Metabolic Resistance to Acetolactate Synthase Inhibiting Herbicide Tribenuron
      Methyl in Descurainia sophia L. Mediated by Cytochrome P450 Enzymes.
AB  - Descurainia sophia is one of the most notorious broadleaf weeds in China and has
      evolved extremely high resistance to acetolactate synthase (ALS)-inhibiting
      herbicide tribenuron-methyl. The target-site resistance due to ALS gene mutations
      was well-known, while the non-target-site resistance is not yet well
      characterized. Metabolic resistance, which is conferred by enhanced rates of
      herbicide metabolism, is the most important NTSR. To explore the mechanism of
      metabolic resistance underlying resistant (R) D. sophia plants, tribenuron-methyl
      uptake and metabolism levels, qPCR reference gene stability, and candidate P450
      genes expression patterns were investigated. The results of liquid chromatography
      mass spectrometry (LC-MS) analysis indicated that the metabolic rates of
      tribenuron-methyl in R plants was significantly faster than in susceptible (S)
      plants, and this metabolism differences can be eliminated by P450 inhibitor
      malathion. The genes for 18S rRNA and TIP41-like were identified as the most
      suitable reference genes using programs of BestKeeper, NormFinder, and geNorm.
      The P450 gene CYP96A146 constitutively overexpressed in R plants compared to S
      plants; this overexpression in R plants can be suppressed by malathion. Taken
      together, a higher expression level of P450 genes, leading to higher tribenuron
      methyl metabolism, appears to be responsible for metabolic resistance to
      tribenuron-methyl in R D. sophia plants.

PMID- 29652485
TI  - Exploiting Potential Inversion for Photoinduced Multielectron Transfer and
      Accumulation of Redox Equivalents in a Molecular Heptad.
AB  - Photoinduced multielectron transfer and reversible accumulation of redox
      equivalents is accomplished in a fully integrated molecular heptad composed of
      four donors, two photosensitizers, and one acceptor. The second reduction of the
      dibenzo[1,2]dithiin acceptor occurs more easily than the first by 1.3 V, and this
      potential inversion facilitates the light-driven formation of a two-electron
      reduced state with a lifetime of 66 ns in deaerated CH3CN. The quantum yield for
      formation of this doubly charge-separated photoproduct is 0.5%. In acidic oxygen
      free solution, the reduction product is a stable dithiol. Under steady-state
      photoirradiation, our heptad catalyzes the two-electron reduction of an aliphatic
      disulfide via thiolate-disulfide interchange. Exploitation of potential inversion
      for the reversible light-driven accumulation of redox equivalents in artificial
      systems is unprecedented and the use of such a charge-accumulated state for
      multielectron photoredox catalysis represents an important proof-of-concept.

PMID- 29652487
TI  - Nanoparticles Conjugated with Photocleavable Linkers for the Intracellular
      Delivery of Biomolecules.
AB  - We report the synthesis and characterization of phototriggerable polymeric
      nanoparticles (NPs) for the intracellular delivery of small molecules and
      proteins to modulate cell activity. For that purpose, several photocleavable
      linkers have been prepared providing diverse functional groups as anchoring
      points for biomolecules.

PMID- 29652488
TI  - Binaphthyl-Bipyridyl Cyclic Dyads as a Chiroptical Switch.
AB  - A series of chiral cyclic dyads, axially chiral binaphthyls linked to a 3,3'
      bipyridyl, was synthesized. The dyad 2 bearing methoxy groups exhibited ON/OFF
      properties in circularly polarized luminescence (CPL), yielding a | glum| of 1.6
      * 10-3 or 0 without any change in fluorescence. This type of CPL switch is
      unprecedented. Regioisomer 4 exhibited a dextro/ levo rotation switching ability
      in [alpha]D. X-ray structures as well as experimental and theoretical analyses
      suggested that the switching properties depended on conformational changes.

PMID- 29652489
TI  - Predominance of N6-Methyladenine-Specific DNA Fragments Enriched by Multiple
      Immunoprecipitation.
AB  - N6-methyladenine (6mA) is a rediscovered DNA modification in eukaryotic genomes.
      To explore the distribution and functions of 6mA, it is of paramount option to
      use immunoprecipitation to select 6mA-containing DNA fragments for genome-wide
      sequencing. Presumably, most of the 6mA-free fragments are removed, and the
      copulling down of the residual is stochastic and sequence-independent and thus
      they should not be called as peaks by computation. Surprisingly, here we show the
      predominance of 6mA-free fragments in the pulled-down fractions. By taking
      advantage of the submicromolar affinity of the antibodies, we further develop an
      elegant, multiple-round immunoprecipitation (MrIP) approach and show that 6mA
      containing fragments can be enriched over 9100-fold and dominate in the final
      pulled-down fractions. This biochemical approach would greatly reduce the peak
      calling bias, which is caused by handling of dominated 6mA-free DNA fragments
      with an assumption-based algorithm computation and facilitates 6mA-pertinent data
      mining. The MrIP concept is extendable for the genome-wide sequencing of diverse
      DNA modifications.

PMID- 29652490
TI  - Immunoassay Multiplexing on a Complementary Metal Oxide Semiconductor Photodiode
      Array.
AB  - Scalable immunoassay multiplexing offers a route to creating rapid point-of-care
      (POC) diagnostics. We present a method for multiplexing immunoassays on the
      surface of a complementary metal oxide semiconductor (CMOS) sensor array
      integrated circuit (IC) without the use of physical separators such as wells or
      channels. Major advantages of using a CMOS sensor array include low mass
      manufacturing costs, the possibility to multiplex multiple assays on a single IC,
      and improved signal when averaging multiple sensors, along with providing a
      platform where wash steps can be incorporated to maximize selectivity and
      sensitivity compared to paper based lateral flow immunoassay. The device was able
      to differentiate between samples containing either, neither, or both rabbit anti
      mouse (RAM) antibodies and/or anti-HIV gp120 antibodies in serum using a gold
      nanoparticle promoted silver enhancement immunoassay. HIV antibody concentrations
      down to 100 MUg/mL were readily detected, which is three times lower than those
      typically found in infected humans (300-500 MUg/mL), and the limit of detection
      was 10 MUg/mL.

PMID- 29652491
TI  - Inhibition of Voltage-Gated K+ Channel Kv1.5 by Antiarrhythmic Drugs.
AB  - Molecular dynamics simulations are employed to determine the inhibitory
      mechanisms of three drugs, 5-(4-phenoxybutoxy)psoralen (PAP-1), vernakalant, and
      flecainide, on the voltage-gated K+ channel Kv1.5, a target for the treatment of
      cardiac arrhythmia. At neutral pH, PAP-1 is neutral, whereas the other two
      molecules carry one positive charge. We show that PAP-1 forms stable dimers in
      water, primarily through hydrophobic interactions between aromatic rings. All
      three molecules bind to the cavity between the Ile508 and Val512 residues from
      the four subunits of the channel. Once bound, the drug molecules are flexible,
      with the average root-mean-square fluctuation being between 2 and 3 A, which is
      larger than the radius of gyration of a bulky amino acid. The presence of a
      monomeric PAP-1 causes the permeating K+ ion to dehydrate, thereby creating a
      significant energy barrier. In contrast, vernakalant blocks the ion permeation
      primarily via an electrostatic mechanism and, therefore, must be in the
      protonated and charged form to be effective.

PMID- 29652492
TI  - Evidence for the Heaviest Expected Halide Species in Aqueous Solution, At-, by
      Electromobility Measurements.
AB  - At- (astatide) is commonly expected to be the heaviest halide in the halogen
      group. However, there is no proof for the existence of this -1 charged species.
      Furthermore, investigations with astatine are restricted by its specific
      radioactive properties, which entail working at ultratrace concentrations
      (typically less than 10-10 M). In this work, an especially built electromigration
      device is applied to obtain information about the charge/size ratio
      characterizing an ion in aqueous solution. An anionic At species is observed in
      reducing conditions. Moreover, we propose the first absolute mobility value for
      the astatine species in acidic reducing condition: (-8.26 +/- 0.59) * 10-4 cm2.V
      1.s-1. This value appears close to that of I- ((-8.30 +/- 0.33) * 10-4 cm2.V-1.s
      1), which is obtained by the same method. The similar absolute mobilities
      obtained for both ions are coherent with theoretical calculations indicating
      similar diffusion behaviors for At- and I-. This good agreement confirms the
      existence of the At- species.

PMID- 29652493
TI  - Reprogramming Probiotic Lactobacillus reuteri as a Biosensor for Staphylococcus
      aureus Derived AIP-I Detection.
AB  - Gram-positive Staphylococcus aureus infection that results in pneumonia, urinary
      tract infection, and in severe cases, sepsis, has recently been classified as a
      serious threat to public health. Rapid and cost-effective detection of these
      infections are costly and time-consuming. Here, we present probiotic lactic acid
      bacteria engineered to detect autoinducer peptide-I (AIP-I), a quorum sensing
      molecule produced by Staphylococcus sp. during pathogenesis. We achieved this by
      adapting the well-characterized agr quorum sensing ( agrQS) from Staphylococcus
      aureus into Lactobacillus reuteri. The engineered biosensor is able to detect AIP
      I levels in the nanomolar to micromolar range. We further investigated the
      function of the biosensor to detect real-time changes in AIP-I levels to
      understand the dynamics of Staphylococcus aureus under various strenuous
      conditions. The developed sensors would be useful for detection of Staphylococcus
      contamination in hospital settings and for high-throughput drug screening.

PMID- 29652494
TI  - Ligand-Phospholipid Conjugation: A Versatile Strategy for Developing Long-Acting
      Ligands That Bind to Membrane Proteins by Restricting the Subcellular
      Localization of the Ligand.
AB  - We hypothesized that if drug localization can be restricted to a particular
      subcellular domain where their target proteins reside, the drugs could bind to
      their target proteins without being metabolized and/or excreted, which would
      significantly extend the half-life of the corresponding drug-target complex.
      Thus, we designed ligand-phospholipid conjugates in which the ligand is
      conjugated with a phospholipid through a polyethylene glycol linker to restrict
      the subcellular localization of the ligand in the vicinity of the lipid bilayer.
      Here, we present the design, synthesis, pharmacological activity, and binding
      mode analysis of ligand-phospholipid conjugates with muscarinic acetylcholine
      receptors as the target proteins. These results demonstrate that ligand
      phospholipid conjugation can be a versatile strategy for developing long-acting
      ligands that bind to membrane proteins in drug discovery.

PMID- 29652495
TI  - Peptidic Macrocycles - Conformational Sampling and Thermodynamic
      Characterization.
AB  - Macrocycles are of considerable interest as highly specific drug candidates, yet
      they challenge standard conformer generators with their large number of rotatable
      bonds and conformational restrictions. Here, we present a molecular dynamics
      based routine that bypasses current limitations in conformational sampling and
      extensively profiles the free energy landscape of peptidic macrocycles in
      solution. We perform accelerated molecular dynamics simulations to capture a
      diverse conformational ensemble. By applying an energetic cutoff, followed by
      geometric clustering, we demonstrate the striking robustness and efficiency of
      the approach in identifying highly populated conformational states of cyclic
      peptides. The resulting structural and thermodynamic information is benchmarked
      against interproton distances from NMR experiments and conformational states
      identified by X-ray crystallography. Using three different model systems of
      varying size and flexibility, we show that the method reliably reproduces
      experimentally determined structural ensembles and is capable of identifying key
      conformational states that include the bioactive conformation. Thus, the
      described approach is a robust method to generate conformations of peptidic
      macrocycles and holds promise for structure-based drug design.

PMID- 29652496
TI  - Bimolecular Coupling as a Vector for Decomposition of Fast-Initiating Olefin
      Metathesis Catalysts.
AB  - The correlation between rapid initiation and rapid decomposition in olefin
      metathesis is probed for a series of fast-initiating, phosphine-free Ru
      catalysts: the Hoveyda catalyst HII, RuCl2(L)(?CHC6H4- o-O iPr); the Grela
      catalyst nG (a derivative of HII with a nitro group para to O iPr); the Piers
      catalyst PII, [RuCl2(L)(?CHPCy3)]OTf; the third-generation Grubbs catalyst GIII,
      RuCl2(L)(py)2(?CHPh); and dianiline catalyst DA, RuCl2(L)( o-dianiline)(?CHPh),
      in all of which L = H2IMes = N,N'-bis(mesityl)imidazolin-2-ylidene. Prior studies
      of ethylene metathesis have established that various Ru metathesis catalysts can
      decompose by beta-elimination of propene from the metallacyclobutane intermediate
      RuCl2(H2IMes)(kappa2-C3H6), Ru-2. The present work demonstrates that in
      metathesis of terminal olefins, beta-elimination yields only ca. 25-40% propenes
      for HII, nG, PII, or DA, and none for GIII. The discrepancy is attributed to
      competing decomposition via bimolecular coupling of methylidene intermediate
      RuCl2(H2IMes)(?CH2), Ru-1. Direct evidence for methylidene coupling is presented,
      via the controlled decomposition of transiently stabilized adducts of Ru-1,
      RuCl2(H2IMes)Ln(?CH2) (Ln = py n'; n' = 1, 2, or o-dianiline). These adducts were
      synthesized by treating in situ-generated metallacyclobutane Ru-2 with pyridine
      or o-dianiline, and were isolated by precipitating at low temperature (-116 or 
      78  degrees C, respectively). On warming, both undergo methylidene coupling,
      liberating ethylene and forming RuCl2(H2IMes)Ln. A mechanism is proposed based on
      kinetic studies and molecular-level computational analysis. Bimolecular coupling
      emerges as an important contributor to the instability of Ru-1, and a potentially
      major pathway for decomposition of fast-initiating, phosphine-free metathesis
      catalysts.

PMID- 29652486
TI  - Biochemistry and Molecular Biology of Flaviviruses.
AB  - Flaviviruses, such as dengue, Japanese encephalitis, tick-borne encephalitis,
      West Nile, yellow fever, and Zika viruses, are critically important human
      pathogens that sicken a staggeringly high number of humans every year. Most of
      these pathogens are transmitted by mosquitos, and not surprisingly, as the earth
      warms and human populations grow and move, their geographic reach is increasing.
      Flaviviruses are simple RNA-protein machines that carry out protein synthesis,
      genome replication, and virion packaging in close association with cellular lipid
      membranes. In this review, we examine the molecular biology of flaviviruses
      touching on the structure and function of viral components and how these interact
      with host factors. The latter are functionally divided into pro-viral and
      antiviral factors, both of which, not surprisingly, include many RNA binding
      proteins. In the interface between the virus and the hosts we highlight the role
      of a noncoding RNA produced by flaviviruses to impair antiviral host immune
      responses. Throughout the review, we highlight areas of intense investigation, or
      a need for it, and potential targets and tools to consider in the important
      battle against pathogenic flaviviruses.

PMID- 29652497
TI  - Second-Generation Palladium Catalyst System for Transannular C-H
      Functionalization of Azabicycloalkanes.
AB  - This article describes the development of a second-generation catalyst system for
      the transannular C-H functionalization of alicyclic amines. Pyridine- and
      quinoline-carboxylate ligands are shown to be highly effective for increasing the
      reaction rate, yield, and scope of Pd-catalyzed transannular C-H arylation
      reactions of azabicyclo[3.1.0]hexane, azabicyclo[3.1.1]heptane,
      azabicyclo[3.2.1]octane, and piperidine derivatives. Mechanistic studies reveal
      that the pyridine/quinoline-carboxylates play a role in impeding both reversible
      and irreversible catalyst decomposition pathways. These ligands enable the first
      reported examples of the transannular C-H arylation of the ubiquitous tropane, 7
      azanorbornane, and homotropane cores. Finally, the pyridine/quinoline
      carboxylates are shown to promote both transannular C-H arylation and
      transannular C-H dehydrogenation on a homotropane substrate.

PMID- 29652500
TI  - Polyrotaxane Brushes Dynamically Formed at a Water/Elastomer Interface.
AB  - Dense polymer brushes with closely packed rotaxane structures were formed at the
      interface of water and a styrene-butadiene elastomer by spontaneous segregation
      of an amphiphilic polyrotaxane (PR), a mechanically interlocked polymer
      consisting of hydrophobic polybutadiene threading through multiple hydrophilic
      gamma-cyclodextrin (gamma-CD) derivatives. Segregation of PR at the
      water/elastomer interface was suggested by X-ray photoelectron spectroscopy. The
      polymer brush structure at the water interface was investigated using neutron
      reflectometry. Brush structures were found to depend on the number of CDs on the
      PRs; the PR with a small number of CDs formed a thinner and homogeneous brush,
      whereas the PR with a higher number of CDs formed a thicker and less-ordered
      brush. These PR-brushes showed protein repulsion, resulting from the surface
      hydrated brush layer preventing direct contact of proteins.

PMID- 29652498
TI  - Suzuki-Miyaura Coupling of Simple Ketones via Activation of Unstrained Carbon
      Carbon Bonds.
AB  - Here, we describe that simple ketones can be efficiently employed as
      electrophiles in Suzuki-Miyaura coupling reactions via catalytic activation of
      unstrained C-C bonds. A range of common ketones, such as cyclopentanones,
      acetophenones, acetone and 1-indanones, could be directly coupled with various
      arylboronates in high site-selectivity, which offers a distinct entry to more
      functionalized aromatic ketones. Preliminary mechanistic study suggests that the
      ketone alpha-C-C bond was cleaved via oxidative addition.

PMID- 29652499
TI  - Rapid Sampling of Hydrogen Bond Networks for Computational Protein Design.
AB  - Hydrogen bond networks play a critical role in determining the stability and
      specificity of biomolecular complexes, and the ability to design such networks is
      important for engineering novel structures, interactions, and enzymes. One key
      feature of hydrogen bond networks that makes them difficult to rationally
      engineer is that they are highly cooperative and are not energetically favorable
      until the hydrogen bonding potential has been satisfied for all buried polar
      groups in the network. Existing computational methods for protein design are ill
      equipped for creating these highly cooperative networks because they rely on
      energy functions and sampling strategies that are focused on pairwise
      interactions. To enable the design of complex hydrogen bond networks, we have
      developed a new sampling protocol in the molecular modeling program Rosetta that
      explicitly searches for sets of amino acid mutations that can form self-contained
      hydrogen bond networks. For a given set of designable residues, the protocol
      often identifies many alternative sets of mutations/networks, and we show that it
      can readily be applied to large sets of residues at protein-protein interfaces or
      in the interior of proteins. The protocol builds on a recently developed method
      in Rosetta for designing hydrogen bond networks that has been experimentally
      validated for small symmetric systems but was not extensible to many larger
      protein structures and complexes. The sampling protocol we describe here not only
      recapitulates previously validated designs with performance improvements but also
      yields viable hydrogen bond networks for cases where the previous method fails,
      such as the design of large, asymmetric interfaces relevant to engineering
      protein-based therapeutics.

PMID- 29652501
TI  - From Dot to Ring: The Role of Friction in the Deposition Pattern of a Drying
      Colloidal Suspension Droplet.
AB  - The deposition of particles on a substrate by drying a colloidal suspension
      droplet is at the core of applications ranging from traditional printing on paper
      to printable electronics or photovoltaic devices. The self-pinning induced by the
      accumulation of particles at the contact line plays an important role in the
      formation of a deposit. In this article, we investigate, both numerically and
      theoretically, the effect of friction between the particles and the substrate on
      the deposition pattern. Without friction, the contact line shows a stick-slip
      behavior and a dotlike deposit is left after the droplet is evaporated. By
      increasing the friction force, we observe a transition from a dotlike to a
      ringlike deposit. We propose a theoretical model to predict the effective radius
      of the particle deposit as a function of the friction force. Our theoretical
      model predicts a critical friction force when self-pinning happens and the
      effective radius of deposit increases with increasing friction force, confirmed
      by our simulation results. Our results can find implications for developing
      active control strategies for the deposition of drying droplets.

PMID- 29652503
TI  - Red/Green Color Tuning of Visual Rhodopsins: Electrostatic Theory Provides a
      Quantitative Explanation.
AB  - We present a structure-based theory of the long-wavelength (red/green) color
      tuning in visual rhodopsins and its application to the analysis of site-directed
      mutagenesis experiments. Using a combination of electrostatic and molecular
      mechanics methods, we explain the measured mutant-minus-wild-type absorption
      shifts and conclude that the dominant mechanism of the color tuning in these
      systems is electrostatic pigment-protein coupling. An important element of our
      analysis is the independent determination of protonation states of titratable
      residues in the wild type and the mutant protein as well as the self-consistent
      reoptimization of hydrogen atom positions, which includes the relaxation of the
      hydrogen bonding network and the reorientation of water molecules. On the basis
      of this analysis, we propose a "dipole-orientation rule" according to which both
      the position and the orientation of a polar group introduced in the protein
      environment determine the direction of the transition energy shift of the retinal
      chromophore.

PMID- 29652502
TI  - Ultrafast Photodynamics of Cyano-Functionalized [FeFe] Hydrogenase Model
      Compounds.
AB  - [FeFe] hydrogenases are efficient enzymes that produce hydrogen gas under mild
      conditions. Synthetic model compounds containing all CO or mixed CO/PMe3 ligands
      were previously studied by us and others with ultrafast ultraviolet or visible
      pump-infrared probe spectroscopy in an effort to better understand the function
      and interactions of the active site with light. Studies of anionic species
      containing cyano groups, which more closely match the biological active site,
      have been elusive. In this work, two model compounds dissolved in room
      temperature acetonitrile solution were examined: [Fe2(MU-S2C3H6)(CO)4(CN)2]2- (1)
      and [Fe2(MU-S2C2H4)(CO)4(CN)2]2- (2). These species exhibit long-lived transient
      signals consistent with loss of one CO ligand with potential isomerization of
      newly formed ground electronic state photoproducts, as previously observed with
      all-CO and CO/PMe3-containing models. We find no evidence for fast (ca. 150 ps)
      relaxation seen in the all-CO and CO/PMe3 compounds because of the absence of the
      metal-to-metal charge transfer band in the cyano-functionalized models. These
      results indicate that incorporation of cyano ligands may significantly alter the
      electronic properties and photoproducts produced immediately after
      photoexcitation, which may influence the catalytic activity of model compounds
      when attached to photosensitizers.

PMID- 29652504
TI  - Role of Vibrational Dynamics on Excited-State Electronic Coherence in a Binuclear
      Platinum Complex.
AB  - Long-lived quantum coherence between excited electronic states can enable highly
      efficient energy and charge transport processes in chemical systems. Recent pump
      probe experiments on binuclear platinum complexes identified persistent, periodic
      beating of transient absorption anisotropy signals, indicating long excited-state
      coherence lifetimes. Our previous simulations of the electronic dynamics of these
      complexes indicate that coherence lifetimes are sensitive to the balance between
      competitive electronic couplings. The complexes with shorter Pt-Pt distances
      underwent no appreciable dephasing in the limit of static nuclei, motivating the
      inclusion of nuclear motion into our simulations. The tert-butyl-substituted
      complex is studied in this work using the Ehrenfest method for mixed quantum
      classical dynamics to investigate the role of vibrational dynamics on a complex
      shown to support long coherence lifetimes. Results indicate that the inclusion of
      excited-state vibrations drives a rapid collapse of the two-state coherence prior
      to the experimentally determined intersystem crossing. This further suggests
      singlet excited-state coherences may not be prerequisites for long-lived triplet
      coherences.

PMID- 29652505
TI  - Dissecting Nanosecond Dynamics in Membrane Proteins with Dipolar Relaxation upon
      Tryptophan Photoexcitation.
AB  - The structural dynamics of proteins on the nanosecond time scale can be probed
      with dipolar relaxation in response to photoexcitation of intrinsic tryptophan
      (Trp) residues. For membrane proteins, however, the complexity due to overlapping
      contributions from the protein itself, the membrane mimic, and the aqueous
      solvent impairs detailed analysis and interpretation. To disentangle these
      contributions, we measured time-resolved emission spectra of Trp in the protein
      Mistic in detergent micelles of various polarities. By comparison with Trp
      analogues in water and micelles, we could dissect the contributions from
      hydration, micelle, and protein matrix to dipolar relaxation on the nanosecond
      time scale. Our results demonstrate that ultrafast, subnanosecond relaxation
      reports on the extent of Trp shielding from water, with micelle and protein
      moieties making additive contributions. By contrast, relaxation in the low
      nanosecond regime is due to dipolar rearrangement of micelle and protein moieties
      upon photoexcitation, thereby probing conformational dynamics around the
      intrinsic fluorophore.

PMID- 29652506
TI  - On-the-Fly Ab Initio Semiclassical Evaluation of Absorption Spectra of Polyatomic
      Molecules beyond the Condon Approximation.
AB  - To evaluate vibronic spectra beyond the Condon approximation, we extend the on
      the-fly ab initio thawed Gaussian approximation by considering the Herzberg
      Teller contribution due to the dependence of the electronic transition dipole
      moment on nuclear coordinates. The extended thawed Gaussian approximation is
      tested on electronic absorption spectra of the phenyl radical and benzene;
      calculated spectra reproduce experimental data and are much more accurate than
      standard global harmonic approaches, confirming the significance of
      anharmonicity. Moreover, the extended method provides a tool to quantify the
      Herzberg-Teller contribution; we show that in the phenyl radical, anharmonicity
      outweighs the Herzberg-Teller contribution, whereas in benzene, the Herzberg
      Teller contribution is essential because the transition is electronically
      forbidden and the Condon approximation yields a zero spectrum. Surprisingly, both
      adiabatic harmonic spectra outperform those of the vertical harmonic model, which
      describes the Franck-Condon region better. Finally, we provide a simple recipe
      for orientationally averaging spectra, valid beyond the Condon approximation, and
      a relation among the transition dipole, its gradient, and nonadiabatic coupling
      vectors.

PMID- 29652507
TI  - Electroactive Ferrocene at or near the Surface of Metal-Organic Framework UiO-66.
AB  - Here, we describe the installation of a ferrocene derivative on and within the
      archetypal metal-organic framework (MOF), UiO-66, by solvent-assisted ligand
      incorporation. Thin films of the resulting material show a redox peak
      characteristic of the Fc/Fc+ couple, as measured by cyclic voltammetry.
      Consistent with restriction of redox reactivity solely to Fc molecules sited at
      or near the external surfaces of MOF crystallites, chronoamperometry measurements
      indicate that less than 20% of the installed Fc molecules are electrochemically
      active. Charge-transport diffusion coefficients, DCT, of 6.1 +/- 0.8 * 10-11 and
      2.6 +/- 0.2 * 10-9 cm2/s were determined from potential step measurements,
      stepping oxidatively and reductively, respectively. The 40-fold difference in DCT
      values contrasts with the expectation, for simple systems, of identical values
      for oxidation-driven versus reduction-driven charge transport. The findings have
      implications for the design of MOFs suitable for delivery of redox equivalents to
      framework-immobilized electrocatalysts and/or delivery of charges from a
      chromophoric MOF film to an underlying electrode, processes that may be central
      to MOF-facilitated conversion of solar energy to chemical or electrical energy.

PMID- 29652508
TI  - Patterning of Wrinkled Polymer Surfaces by Single-Step Electron Irradiation.
AB  - A novel yet simple approach to fabricate and pattern wrinkled surfaces on
      polymers is presented. Only by irradiating an electron beam onto a polymer,
      wrinkles are created on the polymer surface. Electron irradiation produces a
      bilayer polymeric structure comprising a degrading upper layer and a pristine
      bottom layer. Electron irradiation also increases the polymer surface temperature
      to a point much higher than the glass-transition temperature of the upper layer,
      leading to drastic thermal expansion of the upper layer. As a result, significant
      compressive force is applied to form surface wrinkles. The mechanism behind the
      wrinkle formation and the effects of electron irradiation parameters on the
      wrinkle characteristics are discussed. In addition, by this electron irradiation
      approach, a patterned wrinkle structure is uniquely prepared.

PMID- 29652509
TI  - Exciton-Delocalizing Ligands Can Speed Up Energy Migration in Nanocrystal Solids.
AB  - Researchers have long sought to use surface ligands to enhance energy migration
      in nanocrystal solids by decreasing the physical separation between nanocrystals
      and strengthening their electronic coupling. Exciton-delocalizing ligands, which
      possess frontier molecular orbitals that strongly mix with nanocrystal band-edge
      states, are well-suited for this role because they can facilitate carrier-wave
      function extension beyond the nanocrystal core, reducing barriers for energy
      transfer. This report details the use of the exciton-delocalizing ligand
      phenyldithiocarbamate (PDTC) to tune the transport rate and diffusion length of
      excitons in CdSe nanocrystal solids. A film composed of oleate-terminated CdSe
      nanocrystals is subjected to a solid-state ligand exchange to replace oleate with
      PDTC. Exciton migration in the films is subsequently investigated by femtosecond
      transient absorption. Our experiments indicate that the treatment of nanocrystal
      films with PDTC leads to rapid (~400 fs) downhill energy migration (~80 meV),
      while no such migration occurs in oleate-capped films. Kinetic Monte Carlo
      simulations allow us to extract both rates and length scales for exciton
      diffusion in PDTC-treated films. These simulations reproduce dynamics observed in
      transient absorption measurements over a range of temperatures and confirm
      excitons hop via a Miller-Abrahams mechanism. Importantly, our experiments and
      simulations show PDTC treatment increases the exciton hopping rate to 200 fs, an
      improvement of 5 orders of magnitude relative to oleate-capped films. This
      exciton hopping rate stands as one of the fastest determined for CdSe solids. The
      facile, room-temperature processing and improved transport properties offered by
      the solid-state exchange of exciton-delocalizing ligands show they offer promise
      for the construction of strongly coupled nanocrystal arrays.

PMID- 29652510
TI  - Sequential Induction of Chirality in Helical Polymers: From the Stereocenter to
      the Achiral Solvent.
AB  - Several steps of chiral induction have been detected in poly(phenylacetylene)s
      among their different hierarchical levels of chirality by vibrational circular
      dichroism, namely, (i) from the stereogenic centers to the innermost
      polyacetylene helical covalent backbone (helixint), (ii) from this to the
      external helix (helixext) formed by the side phenyl pendants that form a
      complementary helix or counter-helix, and (iii) from this pendant helix to the
      helical solvation sphere (helixsolv.), the last one being observed along this
      work. The pendant to polyene backbone chiral induction determines the helical
      structure adopted by the polymer and therefore the solvation helix. This helical
      structure is promoted by two mechanisms: steric effects and hydrogen bonding. An
      important finding concerns the demonstration by VCD of how an achiral solvent
      becomes chirally organized owing to the template effect of the covalent polymer
      helices, an effect that is silent to other structural techniques such as ECD or
      AFM and that hence significantly broadens the scope of these previous analyses.

PMID- 29652511
TI  - Highly Chemoselective NH- and O-Transfer to Thiols Using Hypervalent Iodine
      Reagents: Synthesis of Sulfonimidates and Sulfonamides.
AB  - Aryl thiols can be selectively converted to sulfonimidates or sulfonamides with
      three new S-X connections being made selectively in one pot. Using hypervalent
      iodine reagents in the presence of ammonium carbamate, NH- and O-groups are
      transferred under mild and practical conditions. Reducing the loading of ammonium
      carbamate changed the product distribution, converting the sulfonimidate to the
      sulfonamide. Studies into the possible intermediate species are presented,
      suggesting that multiple pathways may be possible via sulfinate esters, or
      related intermediates, with each species forming the same products.

PMID- 29652513
TI  - An Experimental Test of the Roles of Audience Involvement and Message Frame in
      Shaping Public Reactions to Celebrity Illness Disclosures.
AB  - Much research has investigated what happens when celebrities disclose an illness
      (via media) to the public. While audience involvement (i.e., identification and
      parasocial relationships) is often the proposed mechanism linking illness
      disclosures with audience behavior change, survey designs have prevented
      researchers from understanding if audience involvement prior to the illness
      disclosure actually predicts post-disclosure emotions, cognitions, and behaviors.
      Rooted in previous work on audience involvement as well as the Extended Parallel
      Process Model, the present study uses a national online experiment (N = 1,068) to
      test how pre-disclosure audience involvement may initiate post-disclosure effects
      for the message context of skin cancer. The data demonstrate that pre-disclosure
      audience involvement as well as the celebrity's framing of the disclosure can
      shape emotional responses (i.e., fear and hope), and that cognitive perceptions
      of the illness itself also influence behavioral intentions.

PMID- 29652514
TI  - "NQO1 Gene C609T Polymorphism (dbSNP: rs1800566) and Digestive Tract Cancer Risk:
      A Meta-Analysis."
AB  - Several studies reported that polymorphism C609T (rs1800566) in (NAD(P)H):
      quinoneoxidoreductase 1 (NQO1) gene is associated with risk to digestive tract
      (DT) cancers, like esophageal cancer (EC), gastric cancer (GC), and colorectal
      cancer (CRC). Authors conducted a meta-analysis to investigate association
      between C609T polymorphism and DT cancer risk. Eligible studies were extracted
      from the databases of PubMed, Google Scholar, Science Direct, and Springer Link.
      All retrieved articles were evaluated. All statistical analyses were performed
      using Open Meta-Analyst and MIX1.7 programs. A total of 34 studies including
      12,043 DT cancer cases and 15,209 healthy controls were included in the present
      meta- analysis. Results of meta-analysis revealed a significant association
      between NQO1 C609T polymorphism and DT cancer risk adopting all 5 genetic models
      (T vs. C: OR = 1.21, 95% CI = 1.11-1.31, p < 0.001; TT vs. CC: OR = 1.48, 95% CI
      = 1.22-1.79, p < 0.001; TT + CT vs. CC: OR = 1.23, 95% CI = 1.12-1.35, p < 0.001;
      TT vs. CT + CC: OR = 1.36, 95% CI = 1.15-1.60, p < 0.001; CT vs. CC: OR = 1.16,
      95% CI = 1.07-1.27, p < 0.001). In the stratified analysis based on cancer types,
      significant associations were observed between NQO1 C609T polymorphism and GC (OR
      = 1.38, 95% CI = 1.11-1.72, p = 0.003) and CRC (OR = 1.18, 95% CI = 1.06-1.30, p
      = 0.001), but not with EC (OR = 1.16, 95% CI = 0.99-1.35, p = 0.06). Furthermore,
      stratified analysis based on ethnicity indicated that there was a significant
      association between NQO1 C609T polymorphism and DT cancer risk in the Asian (TT
      vs. CC: OR = 1.55, 95% CI = 1.21-2.00, p <= 0.001) as well as in Caucasian
      populations (TT vs. CC: OR = 1.34, 95% CI = 1.04-1.73, p = 0.02). In conclusion,
      the results of meta-analysis suggested that the NQO1 C609T polymorphism is a risk
      factor for DT cancers, including GC and CRC.

PMID- 29652515
TI  - Structure and Function of the 26S Proteasome.
AB  - As the endpoint for the ubiquitin-proteasome system, the 26S proteasome is the
      principal proteolytic machine responsible for regulated protein degradation in
      eukaryotic cells. The proteasome's cellular functions range from general protein
      homeostasis and stress response to the control of vital processes such as cell
      division and signal transduction. To reliably process all the proteins presented
      to it in the complex cellular environment, the proteasome must combine high
      promiscuity with exceptional substrate selectivity. Recent structural and
      biochemical studies have shed new light on the many steps involved in proteasomal
      substrate processing, including recognition, deubiquitination, and ATP-driven
      translocation and unfolding. In addition, these studies revealed a complex
      conformational landscape that ensures proper substrate selection before the
      proteasome commits to processive degradation. These advances in our understanding
      of the proteasome's intricate machinery set the stage for future studies on how
      the proteasome functions as a major regulator of the eukaryotic proteome.

PMID- 29652516
TI  - Attitudes and Perception Towards Eye Donation in Patients with Corneal Disease: A
      Case-controlled Population-based Study.
AB  - PURPOSE: To assess awareness, barriers, and misconceptions related to eye
      donation in people with corneal disease as compared to controls in a population
      setting. MATERIALS AND METHODS: A population-based study was conducted in 25
      randomly selected clusters of Rural Gurgaon, Haryana, India, as part of the CORE
      (Cornea Opacity Rural Epidemiological) study. In addition to ophthalmic
      examination, knowledge and perceptions regarding eye donation were assessed
      through a validated questionnaire. The questionnaire captured the
      sociodemographic factors influencing awareness regarding eye donation in
      participants with corneal disease and twice the number of age- and gender-matched
      controls recruited from the same study clusters. Descriptive statistics were
      computed along with multivariable logistic regression analysis to determine
      associated factors for awareness of eye donation. RESULTS: In the CORE study, 452
      participants had corneal opacities on ocular examination. Of these, 442 were
      assessed for eye donation awareness. Additionally, 884 age- and gender-matched
      controls were recruited. The mean age of cases and controls was 60.9 +/- 15.5 and
      59.6 +/- 14.3 years, respectively. Awareness of eye donation in cases and
      controls was 46.4% (n = 205 of 442) and 52.3% (n = 462 of 884), respectively (P =
      0.044). Educational status was an important factor determining knowledge about
      eye donation in both cases and controls (P = < 0.001). Major barriers reported
      for not pledging eyes were lack of willingness (36.7%) and ignorance (15.3%).
      Common misconceptions like eyes could be donated before death or even after 24 h
      of death and that any type of blindness could be treated with corneal
      transplantation were prevalent. CONCLUSIONS: The study demonstrated that although
      there is substantial awareness about eye donation, there are numerous barriers in
      this population that need to be resolved to improve donation rates. Additional
      efforts are needed to translate this awareness into actual eye donation in both
      cases with corneal disease and controls.

PMID- 29652517
TI  - Angiotensin-(1-7) Attenuated Cigarette Smoking-related Pulmonary Fibrosis via
      Improving the Impaired Autophagy Caused by Nicotinamide Adenine Dinucleotide
      Phosphate Reduced Oxidase 4-Dependent Reactive Oxygen Species.
AB  - Cigarette smoking is acknowledged as the major risk factor of pulmonary fibrosis.
      Angiotensin (Ang) II has been reported to aggravate smoking-induced lung
      fibrosis, whereas the effect of Ang-(1-7) on smoking-related lung fibrosis
      remains unknown. The autophagy, being activated by reactive oxygen species (ROS),
      is identified as a novel mechanism of pulmonary fibrosis. However, whether
      autophagy is involved in regulation of smoking-induced lung fibrosis still needs
      investigation. Here, we aim to investigate the effect of Ang-(1-7) on smoking
      related lung fibrosis by the regulation of autophagy and ROS. In vivo, Ang-(1-7)
      was constantly infused into passive smoking rats for 8 weeks. In vitro, primary
      lung fibroblasts were pretreated with antioxidant, nicotinamide adenine
      dinucleotide phosphate reduced oxidase (NOX) 4 siRNA, or light chain (LC) 3B
      siRNA before exposure to cigarette smoke extract (CSE). GFP-mCherry red
      fluorescent protein-LC3 advenovirus was introduced to evaluate the autophagic
      flux in cells. We found that Ang-(1-7) reduced hydrogen peroxide (H2O2)
      concentration, protein levels of NOX4, and autophagy impairment, as well as
      improving lung fibrosis induced by smoking stimulation in vivo. In vitro, CSE
      treatment elevated NOX4 protein expression and ROS production, resulting in the
      accumulation of impaired autophagosomes in fibroblasts. LC3B depletion enhanced
      CSE-induced collagen synthesis. Treatment with antioxidants or NOX4 siRNA
      inhibited CSE-induced insufficient autophagic flux and collagen production. In
      contrast, the action of Ang-(1-7) opposed the effects of CSE. In conclusion, Ang
      (1-7) improves smoking-induced pulmonary fibrosis via attenuating the impaired
      autophagy caused by NOX4-dependent ROS in vivo and in vitro.

PMID- 29652519
TI  - Drug-Induced Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Call for
      Optimum Patient Stratification and Theranostics via Pharmacogenomics.
AB  - The Global Genomic Medicine Collaborative, a multinational coalition of genomic
      and policy experts working to implement genomics in clinical care, considers
      pharmacogenomics to be among the first areas in genomic medicine that can provide
      guidance in routine clinical practice, by linking genetic variation and drug
      response. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are
      severe life-threatening reactions to medications with a high incidence worldwide.
      Genomic screening prior to drug administration is a key opportunity and potential
      paradigm for using genomic medicine to reduce morbidity and mortality and
      ultimately eliminate one of the most devastating adverse drug reactions. This
      review focuses on the current understanding of the surveillance, pathogenesis,
      and treatment of SJS/TEN, including the role of genomics and pharmacogenomics in
      the etiology, treatment, and eradication of preventable causes of drug-induced
      SJS/TEN. Gaps, unmet needs, and priorities for future research have been
      identified for the optimal management of drug-induced SJS/TEN in various ethnic
      populations. Pharmacogenomics holds great promise for optimal patient
      stratification and theranostics, yet its clinical implementation needs to be cost
      effective and sustainable.

PMID- 29652518
TI  - Discoidin Domain Receptor 2 Signaling Regulates Fibroblast Apoptosis through
      PDK1/Akt.
AB  - Progressive fibrosis is a complication of many chronic diseases, and
      collectively, organ fibrosis is the leading cause of death in the United States.
      Fibrosis is characterized by accumulation of activated fibroblasts and excessive
      deposition of extracellular matrix proteins, especially type I collagen.
      Extensive research has supported a role for matrix signaling in propagating
      fibrosis, but type I collagen itself is often considered an end product of
      fibrosis rather than an important regulator of continued collagen deposition.
      Type I collagen can activate several cell surface receptors, including
      alpha2beta1 integrin and discoidin domain receptor 2 (DDR2). We have previously
      shown that mice deficient in type I collagen have reduced activation of DDR2 and
      reduced accumulation of activated myofibroblasts. In the present study, we found
      that DDR2-null mice are protected from fibrosis. Surprisingly, DDR2-null
      fibroblasts have a normal and possibly exaggerated activation response to
      transforming growth factor-beta and do not have diminished proliferation compared
      with wild-type fibroblasts. DDR2-null fibroblasts are significantly more prone to
      apoptosis, in vitro and in vivo, than wild-type fibroblasts, supporting a
      paradigm in which fibroblast resistance to apoptosis is critical for progression
      of fibrosis. We have identified a novel molecular mechanism by which DDR2 can
      promote the activation of a PDK1 (3-phosphoinositide dependent protein kinase
      1)/Akt survival pathway, and we have found that inhibition of PDK1 can augment
      fibroblast apoptosis. Furthermore, our studies demonstrate that DDR2 expression
      is heavily skewed to mesenchymal cells compared with epithelial cells and that
      idiopathic pulmonary fibrosis cells and tissue demonstrate increased activation
      of DDR2 and PDK1. Collectively, these findings identify a promising target for
      fibrosis therapy.

PMID- 29652521
TI  - Social Media Use and Well-Being in People with Physical Disabilities: Influence
      of SNS and Online Community Uses on Social Support, Depression, and Psychological
      Disposition.
AB  - This study examined the relationships across social media use, social support,
      depression, and general psychological disposition among people with movement or
      mobility disabilities in Korea. First, with survey data (n = 91) collected from
      users of social network sites (SNSs) and online communities, hypotheses regarding
      positive associations between intensity of an individual's engagement in social
      media and four different types of social support-emotional, instrumental,
      informational, and appraisal support-were tested as well as hypotheses regarding
      mediation effects of the social support variables in the association between
      social media use and depression. Second, through focus group interviews (n = 15),
      influences of social media use on social support were more thoroughly explored as
      well as their influences on general psychological disposition. Results from
      hierarchical regression analyses confirmed that both intensity of SNS use and
      online community use significantly predicted instrumental, informational, and
      appraisal support, while they did not predict emotional support. Further
      regression and Sobel tests showed that higher levels of intensity of SNS use and
      of online community use both led to lower levels of depression through the
      mediation of instrumental and informational support. Analysis of the interviews
      further revealed the positive roles of social media use in building social
      support and healthy psychological dispositions. However, analysis also revealed
      some negative consequences of and limitations to social media use for those with
      physical disabilities. These findings expand our knowledge of the context and
      implications of engaging in online social activities for people with physical
      disabilities.

PMID- 29652520
TI  - Hemolysis-induced Lung Vascular Leakage Contributes to the Development of
      Pulmonary Hypertension.
AB  - Although hemolytic anemia-associated pulmonary hypertension (PH) and pulmonary
      arterial hypertension (PAH) are more common than the prevalence of idiopathic PAH
      alone, the role of hemolysis in the development of PAH is poorly characterized.
      We hypothesized that hemolysis independently contributes to PAH pathogenesis via
      endothelial barrier dysfunction with resulting perivascular edema and
      inflammation. Plasma samples from patients with and without PAH (both confirmed
      by right heart catheterization) were used to measure free hemoglobin (Hb) and its
      correlation with PAH severity. A sugen (50 mg/kg)/hypoxia (3 wk)/normoxia (2 wk)
      rat model was used to elucidate the role of free Hb/heme pathways in PAH. Human
      lung microvascular endothelial cells were used to study heme-mediated endothelial
      barrier effects. Our data indicate that patients with PAH have increased levels
      of free Hb in plasma that correlate with PAH severity. There is also a
      significant accumulation of free Hb and depletion of haptoglobin in the rat
      model. In rats, perivascular edema was observed at early time points concomitant
      with increased infiltration of inflammatory cells. Heme-induced endothelial
      permeability in human lung microvascular endothelial cells involved activation of
      the p38/HSP27 pathway. Indeed, the rat model also exhibited increased activation
      of p38/HSP27 during the initial phase of PH. Surprisingly, despite the increased
      levels of hemolysis and heme-mediated signaling, there was no heme oxygenase-1
      activation. This can be explained by observed destabilization of HIF-1a during
      the first 2 weeks of PH regardless of hypoxic conditions. Our data suggest that
      hemolysis may play a significant role in PAH pathobiology.

PMID- 29652522
TI  - Realizing the Paris Climate Agreement to Improve Cardiopulmonary Health. Where
      Science Meets Policy.

PMID- 29652524
TI  - Smoking, ADHD, and Problematic Video Game Use: A Structural Modeling Approach.
AB  - Problematic video game use (PVGU), or addiction-like use of video games, is
      associated with physical and mental health problems and problems in social and
      occupational functioning. Possible correlates of PVGU include frequency of play,
      cigarette smoking, and attention deficit hyperactivity disorder (ADHD). The aim
      of the current study was to explore simultaneously the relationships among these
      variables as well as test whether two separate measures of PVGU measure the same
      construct, using a structural modeling approach. Secondary data analysis was
      conducted on 2,801 video game users (Mage = 22.43 years, standard deviation
      [SD]age = 4.7; 93 percent male) who completed an online survey. The full model
      fit the data well: chi2 (2) = 2.017, p > 0.05; root mean square error of
      approximation (RMSEA) = 0.002 (90% CI [0.000-0.038]); comparative fit index (CFI)
      = 1.000; standardized root mean square residual (SRMR) = 0.004; and all
      standardized residuals <|0.1|. All freely estimated paths were statistically
      significant. ADHD symptomatology, smoking behavior, and hours of video game use
      explained 41.8 percent of variance in PVGU. Tracking these variables may be
      useful for PVGU prevention and assessment. Young's Internet Addiction Scale,
      adapted for video game use, and the Problem Videogame Playing Scale both loaded
      strongly onto a PVGU factor, suggesting that they measure the same construct,
      that studies using either measure may be compared to each other, and that both
      measures may be used as a screener of PVGU.

PMID- 29652523
TI  - Attitudes on technological, social, and behavioral economic strategies to reduce
      cellphone use among teens while driving.
AB  - OBJECTIVE: The majority of U.S. teens admit to handheld cellphone use while
      driving, an increasingly common cause of crashes. Attitudes toward novel
      cellphone applications and settings that block use while driving are poorly
      understood, potentially limiting uptake. We examined teens' willingness to reduce
      cellphone use while driving and perceptions of potential strategies to limit this
      behavior. METHODS: Teen drivers (n = 153) aged 16-17 who owned smartphones and
      admitted to texting while driving completed an online survey. Survey instruments
      measured willingness to give up cellphone use and perceptions of technological
      and behavioral economic strategies to reduce cellphone use while driving. We used
      chi-square tests to test the hypothesis that willingness to give up certain types
      of cellphone use while driving and the perceptions of strategies to reduce
      cellphone use while driving would differ by self-reported frequency of texting
      while driving in the past 30 days (low [1-5 days] vs. high [6 or more days]).
      RESULTS: Most teens were willing or somewhat willing to give up reading texts
      (90%), sending texts (95%), and social media (99%) while driving. However, they
      were not willing to give up navigation (59%) and music applications (43%). Those
      who engaged in high-frequency texting while driving were more likely to say that
      they were not willing to give up navigation applications (73 vs. 44%, P <.001),
      music applications (54 vs. 32%, P <.001), and reading texts (15 vs. 4%, P =.029).
      Overall, the following strategies where rated as likely to be very effective for
      reducing texting while driving: gain-framed financial incentives (75%), loss
      framed financial incentives (63%), group-based financial incentives (58%),
      insurance discounts (53%), automatic phone locking while driving (54%), e-mail
      notifications to parents (47%), automated responses to incoming texts (42%), peer
      concern (18%), and parental concern (15%). Those who engaged in high-frequency
      texting while driving were less likely to say that following strategies would be
      very effective: automated responses to incoming texts (33 vs. 53%, P =.016), peer
      concern (9 vs. 29%, P =.002), and parental concern (9 vs. 22%, P =.025). The
      strongest perceived benefit of cellphone blocking apps was decreasing distraction
      (86%). The predominant reason for not wanting to use this technology was not
      wanting parents to monitor their behavior (60%). CONCLUSIONS: Promising
      strategies for increasing acceptance of cellphone blocking technology among teen
      drivers include automated screen locking and permitting hands-free navigation and
      music combined with behavioral economic incentives to sustain engagement.

PMID- 29652525
TI  - 'Reported concussion' time trends within two national health surveys over two
      decades.
AB  - BACKGROUND: An 'epidemic' of concussions has been widely reported. We examined
      the annual incidence of reported concussion or other brain injury, over 20 years
      within Canada in order to explore the magnitude of this reported epidemic.
      METHODS: Two Canadian nationally representative health surveys have serially
      collected injury data associated with disability. The National Population Health
      Survey (NPHS) collected data on 'concussion' (1994-1999), and the Canadian
      Community Health Survey (CCHS) collects data on 'concussion or other brain
      injury' (2000-current). Respondents 12 years and older reporting concussion or
      other brain injury occurring within the previous year were used to produce serial
      incidence data. RESULTS: Nationally representative data were available biennially
      from 1994/95 through 2013/14 with the exception of 2007/08 and 2011/12. Reported
      incidence of concussions, or concussions and other brain injury has been stable
      until 2005/06 when the reported annual incidence started an upward slope to
      levels 250% higher without any apparent stabilization by 2013/14, at which time
      approximately 1 in 200 Canadians 12 years and older reported concussion or other
      brain injury as their most significant injury associated with disability in the
      previous year. CONCLUSIONS: The current pandemic of reported brain injury in
      Canada will have implications for health-care delivery.

PMID- 29652526
TI  - Side Streets and U-Turns: Effects of Context Switching, Direction Switching, and
      Factor Switching on Interitem Correlations and Misresponse Rates.
AB  - This study tested implications of the context switching perspective proposed by
      Hamby, Ickes, and Babcock ( 2016 ). Using trained raters to assess the amount of
      reframing required to interpret the meaning of the subsequent (second) item
      within all adjacent item pairs, we first established that this process variable
      could be measured reliably. Then, in the data for 18 personality measures drawn
      from 3 individual-difference domains, we found that the amount of reframing
      (i.e., context switching) needed to interpret successive items predicted both
      lower interitem correlations and a greater percentage of misresponders.
      Similarly, item pairs that were mismatched in "directional" wording also
      predicted both lower interitem correlations and more misresponders. Finally, item
      pairs representing different factors predicted lower interitem correlations.
      Although the effects of direction switching and factor switching were partially
      mediated by the amount of reframing required, they remained significant even when
      the mediating effect of reframing was statistically controlled. These results
      indicate that interpreting the meaning of test items is a task for which the
      level of difficulty can vary with each successive item, as a function of how the
      current item compares to the previous item in aspects such as its context
      generality or specificity, directional wording, and content domain.

PMID- 29652527
TI  - Contributions to advances in blend pellet products (BPP) research on molecular
      structure and molecular nutrition interaction by advanced synchrotron and globar
      molecular (Micro)spectroscopy.
AB  - To date, advanced synchrotron-based and globar-sourced techniques are almost
      unknown to food and feed scientists. There has been little application of these
      advanced techniques to study blend pellet products at a molecular level. This
      article aims to provide recent research on advanced synchrotron and globar
      vibrational molecular spectroscopy contributions to advances in blend pellet
      products research on molecular structure and molecular nutrition interaction. How
      processing induced molecular structure changes in relation to nutrient
      availability and utilization of the blend pellet products. The study reviews
      Utilization of co-product components for blend pellet product in North America;
      Utilization and benefits of inclusion of pulse screenings; Utilization of
      additives in blend pellet products; Application of pellet processing in blend
      pellet products; Conventional evaluation techniques and methods for blend pellet
      products. The study focus on recent applications of cutting-edge vibrational
      molecular spectroscopy for molecular structure and molecular structure
      association with nutrient utilization in blend pellet products. The information
      described in this article gives better insight on how advanced molecular
      (micro)spectroscopy contributions to advances in blend pellet products research
      on molecular structure and molecular nutrition interaction.

PMID- 29652528
TI  - ERK1/2-Dependent Gene Expression Contributing to TGFbeta-Induced Lens EMT.
AB  - PURPOSE: This study aims to highlight some of the genes that are differentially
      regulated by ERK1/2 signaling in TGFbeta-induced EMT in lens, and their potential
      contribution to this pathological process. MATERIALS AND METHODS: Rat lens
      epithelial explants were cultured with or without TGFbeta over a 3-day-culture
      period to induce EMT, in the presence or absence of UO126 (ERK1/2 signaling
      inhibitor), both prior to TGFbeta-treatment, or 24 or 48 hours after TGFbeta
      treatment. Smad2/3-nuclear immunolabeling was used to indicate active TGFbeta
      signaling, and quantitative RT-PCR was used to analyze changes in the different
      treatment groups in expression of the following representative genes: TGFbeta
      signaling (Smad7, Smurf1, and Rnf111), epithelial markers (Pax6, Cdh1, Zeb1, and
      Zeb2), cell survival/death regulators (Bcl2, Bax, and Bad) and lens mesenchymal
      markers (Mmp9, Fn1, and Col1a1), over the 3 days of culture. RESULTS: ERK1/2 was
      found to regulate the expression of Smurf1, Smad7, Rnf11, Cdh1, Pax6, Zeb1, Bcl2,
      Bax, and Bad genes in lens cells. TGFbeta signaling was evident by nuclear
      localization of Smad2/3 and this was effectively blocked by pre-treatment with
      UO126, but not by post-treatment with this ERK1/2 signaling inhibitor. TGFbeta
      induced the expression of its signaling partners (Smad7, Smurf1, and Rnf111), as
      well as lens mesenchymal genes (Mmp9, Fn1, and Col1a1), consistent with its role
      in inducing an EMT. These TGFbeta-responsive signaling genes, as well as the
      mesenchymal markers, were all positively regulated by ERK1/2-activity. The
      expression levels of the lens epithelial genes we examined, and genes that were
      associated with cell death/survival, were not directly impacted by TGFbeta.
      CONCLUSIONS: TGFbeta-mediated ERK1/2 signaling positively modulates the
      expression of mesenchymal genes in lens epithelial explants undergoing EMT, in
      addition to regulating TGFbeta-mediated regulatory genes. Independent of TGFbeta,
      ERK1/2 activity can also regulate the expression of endogenous lens epithelial
      genes, highlighting its potential key role in regulation of both normal and
      pathological lens cellular processes.

PMID- 29652529
TI  - Neurocognitive Predictors of Clinical Improvement in Selective Serotonin Reuptake
      Inhibitor-Treated Adolescents with Major Depressive Disorder.
AB  - OBJECTIVES: Numerous studies have suggested cognitive deficits as consistently
      associated with adolescent depression. No study to date, however, has assessed
      neurocognitive predictors of selective serotonin reuptake inhibitor (SSRI)
      treatment response in adolescents with depression. This study examined
      neurocognitive tasks at baseline as predictors of clinical improvement with SSRI
      treatment (fluoxetine) at week 6 and 12 in an adolescent population. METHODS:
      Adolescents with depression were recruited from a child and adolescent psychiatry
      outpatient clinic at a university medical center. Twenty-four adolescents (mean
      age 14.8 years) with Major Depressive Disorder completed tasks of the Cambridge
      Neuropsychological Test Automated Battery, including visual memory, executive
      functioning, sustained attention, and impulsivity. Depression severity, measured
      by the Children's Depression Rating Scale-Revised (CDRS-R), was assessed at week
      6 and 12 and clinical improvement was defined as percentage (%) change in CDRS-R
      from baseline. RESULTS: Clinical improvement is noted at both week 6 (mean %
      change in CDRS-R [M] = 46.8, standard deviation [SD] = 51.9) and week 12 (M =
      87.9, SD = 57.2). Results reveal that less difficulty in sustained attention (p =
      0.02), lower impulsivity (p = 0.00), and better planning (p = 0.04) at baseline
      were predictors of greater clinical improvement at week 6. Lower impulsivity at
      baseline remained significantly predictive of clinical improvement at week 12 (p
      = 0.01). CONCLUSION: Neurocognitive assessments could potentially help identify a
      subset of depressed adolescents who may not respond to conventional SSRI
      treatment and who may be better candidates for alternative or augmentation
      treatments.

PMID- 29652530
TI  - Assessing Psychological Adjustment to Congenital Craniofacial Anomalies: An
      Illustration of Methodological Challenges.
AB  - BACKGROUND: Recognition of the challenges inherent in psychology research related
      to cleft lip and/or palate (CL/P) and other craniofacial anomalies (CFAs) is far
      from novel; yet these challenges continue to limit progress within the field. The
      aim of the present article was to illustrate these challenges by utilizing data
      extracted from 2 recent literature reviews pertaining to psychological adjustment
      within CL/P and CFA research. DESIGN: Data relating to 148 CL/P and 41 CFA
      studies were extracted, summarized, and compared, using percentages, figures, and
      chi2 calculations. RESULTS: Comparable patterns were observed in both populations
      in relation to small sample sizes, wide age ranges, a reliance on data collection
      from single sites, and limited global coverage. Similarly, only one-third of all
      studies had used a comparison group, 42% of studies did not include the patient
      perspective, and fewer than 10% of studies had collected data longitudinally.
      Qualitative research was lacking across both populations, but particularly in
      relation to CFA. A higher proportion of CFA studies utilized validated measures
      and were less likely to exclude patients with additional anomalies. CFA studies
      most frequently focused on behavior and overall quality of life, while CL/P
      studies tended to investigate emotional well-being and social experiences.
      CONCLUSIONS: Findings illustrate the variability in research approaches,
      sampling, measurement, and analysis across both populations. There is a pressing
      need to address key methodological issues within craniofacial research and to
      examine the possible similarities and condition-specific differences between CL/P
      and other congenital craniofacial anomalies.

PMID- 29652531
TI  - Adult Narratives of the Psychosocial Impact of Cleft in a Western Australian
      Cohort.
AB  - BACKGROUND: Living with a cleft condition involves many years of
      multidisciplinary therapy, treatment, and surgical intervention. This complex
      process may have both physical and psychosocial long-term impacts. There is
      limited evidence of the psychosocial impact of cleft on individuals in Australia.
      AIM: To obtain an understanding of the adult patient perception of having a cleft
      and explore the impact of the condition on their lives. DESIGN: Qualitative
      methodologies at one case study site in Western Australia. Population of
      Interest: Adults with a cleft lip and/or palate (CL/P) who had received treatment
      at Princess Margaret Hospital, the only treatment center for cleft in Western
      Australia. METHODOLOGY: Individual in-depth semi-structured qualitative
      interviews were conducted and recorded and transcribed for analysis. RESULTS:
      Fifteen adults with a CL/P. Two main themes were identified: lived experience
      (with 3 subthemes: normality, support networks, and impacts in later life) and
      advice to others. The majority of participants reported social rejection and
      isolation, which occurred mostly at school and in some instances at home, but did
      not often last into adulthood. The greatest protective factor was the support of
      family and friends, which if missing during their childhood, was desired and
      appreciated in adulthood. CONCLUSION: Adults with CL/P may require psychosocial
      support from their cleft team including referral to clinicians in adult services.
      There is also the need for earlier psychological interventions and social
      programs to support those with appearance-related social difficulties.

PMID- 29652532
TI  - Comparing Psychological Adjustment Across Cleft and Other Craniofacial
      Conditions: Implications for Outcome Measurement and Intervention.
AB  - Although cleft lip and/or palate (CL/P) has been a focus of psychological
      research for a number of years, investigation of adjustment to other, rarer
      craniofacial anomalies (CFAs) has been scarce. Yet, many features of the journey
      experienced by patients with CL/P could also have relevance for those affected by
      other CFAs and vice versa. This brief article summarizes the literature
      pertaining to psychological adjustment across both craniofacial groups, as
      represented by several prominent review articles. Similarities across the 2
      patient groups in relation to key domains of psychological adjustment and
      corresponding factors are identified. Consequently, a standardized approach to
      measurement across all congenital craniofacial conditions is proposed, alongside
      suggestions for the potential application of similar intervention frameworks and
      clinical approaches.

PMID- 29652533
TI  - Facial and Nasolabial Aesthetics of Complete UCLP Submitted to 2-Stage Palate
      Repair With Vomer Flap.
AB  - OBJECTIVE: To evaluate the aesthetics of nasolabial appearance and facial profile
      of children with unilateral cleft lip and palate (UCLP) submitted to 2-stage
      palate repair with vomerine flap. DESIGN: Retrospective. SETTING: Single center.
      PATIENTS: Forty patients with UCLP, mean age of 7.81 years of both sexes,
      rehabilitated at a single center by 1 plastic surgeon. INTERVENTIONS: Lip and
      anterior palate repair with nasal alar repositioning was performed at 3 to 6
      months of age by Millard technique and vomer flap, respectively. Posterior palate
      was repaired at 18 months by Von Langenbeck technique. MAIN OUTCOME MEASURE(S):
      Four cropped digital facial photographs of each patient were evaluated by 3
      orthodontists to score the nasolabial aesthetics and profile. Frequencies of each
      score as well means and medians were calculated. Kappa test was used for
      evaluating inter- and intrarater reproducibility. RESULTS: The nasal form and
      deviation was scored as good/very good in 70%, fair in 22.5%, and poor in 7.5% of
      the sample. The nasal-subnasal aesthetic was considered good/very good in 55%,
      fair in 30%, and poor in 15% of the sample. The lip vermilion border and the
      white part of surgical scar aesthetics were good/very good in 77.5% and 80%, fair
      in 17.5% for both categories, and poor in 5% and 2.5% of the cases, respectively.
      In all, 67.5% showed convex facial profile, 20% was straight, and 12.5% was
      concave profile. CONCLUSIONS: Two-stage palatoplasty presented an adequate
      aesthetical results for the majority of patients with UCLP in the mixed
      dentition.

PMID- 29652534
TI  - 22q11.2 Deletion Syndrome in Colombian Patients With Syndromic Cleft Lip and/or
      Palate.
AB  - The objective of this work was to identify 22q11.2 chromosomal deletion in
      patients with cleft lip and/or cleft palate and suggestive syndromic phenotype in
      Colombian patients. We studied 49 patients with cleft lip and/or cleft palate,
      exhibiting additional clinical findings linked to 22q11.2 deletion syndrome. All
      patients underwent high-resolution G-banded karyotyping, multiplex ligation
      dependent probe amplification, and clinical evaluation by a geneticist. Seven
      patients presented 22q11.2 deletion and 2 patients had other chromosomal
      abnormalities. In conclusion, this study contributes with new data for genetic
      etiology in syndromic conditions of oral fissures.

PMID- 29652535
TI  - Teachers' Perspectives on the Impact of Cleft Lip and/or Palate During the School
      Years.
AB  - BACKGROUND: Cleft lip and/or palate (CL/P) poses many challenges for those
      affected throughout the school years, with recent studies pointing to a trend in
      poor educational outcomes. Previous research has highlighted the important role
      that teachers play in supporting young people with chronic health conditions yet
      studies in the field of CL/P suggest that teachers may lack knowledge of the
      condition, and underestimate pupils' academic ability. Qualitative investigation
      of the impact of CL/P from the teacher's perspective may provide additional
      insight as well as potential suggestions for improving the school experience for
      affected pupils. METHODS: Twenty UK preschool, primary, and secondary school
      teachers with experience of teaching pupils with CL/P completed an open-ended
      survey, eliciting qualitative data. RESULTS: Qualitative content analysis was
      performed. Data were presented under 5 key headings: Knowledge of CL/P and its
      effects, perceived impact of CL/P on education, teachers' training needs,
      delivery of training, and impact of CL/P on teachers. Teachers were able to
      identify a number of potential social, emotional, and treatment-related
      challenges within the school setting, yet did not believe that CL/P would have a
      long-term impact on pupils' educational achievement. Participating teachers
      reported that cleft-specific training and access to relevant resources would be
      highly beneficial. CONCLUSIONS: Acting as a platform for future research, this
      exploratory study provides insight into the challenges faced by teachers and
      offers suggestions for how to improve teachers' understanding of CL/P, and their
      confidence in dealing with cleft-related issues.

PMID- 29652536
TI  - Computed Tomography-Assisted Auricular Cartilage Graft for Depression of the Alar
      Base in Secondary Unilateral Cleft Lip Repair: A Preliminary Report.
AB  - OBJECTIVES: To evaluate the feasibility, effectiveness, and safety of computed
      tomography-assisted auricular cartilage grafting for treating alar base
      depression secondary to unilateral cleft lip. DESIGN AND SETTING: For patients
      with obvious depression of the alar base, the difference in heights of the alar
      base and the piriform margin between the cleft side and the noncleft side were
      measured with computed tomography. If both were >3.0 mm, the cartilage was
      harvested postauricularly and subdivided into 2 to 4 pieces. A multiple layer
      graft was inserted under the depressed alar base. The procedure was performed
      from 2006 to 2013, and the follow-up period was 3 to 15 months. PARTICIPANTS:
      Chinese patients with alar base depression secondary to unilateral cleft lip were
      selected. INTERVENTION: Suture and cartilage graft techniques. MAIN OUTCOMES
      MEASURES: Differences in bilateral alar base heights and piriform apertures.
      RESULTS: There was no wound dehiscence, exposure of bone, or donor site
      morbidity. The difference in heights in the bilateral alar bases and piriform
      apertures decreased. There were no obvious scars in any of the cases.
      CONCLUSIONS: This technique has several advantages including ease of operation,
      minimal trauma, satisfactory outcomes, and useful references for operation
      provided by computed tomography. It is a superior alternative for reconstruction
      of secondary alar depression.

PMID- 29652537
TI  - Subphenotyping and Classification of Cleft Lip and Alveolus in Adult Unoperated
      Patients: A New Embryological Approach.
AB  - OBJECTIVE: Previously, a new embryological classification was introduced
      subdividing oral clefts into fusion and/or differentiation defects. This
      subdivision was used to classify all subphenotypes of cleft lip with or without
      alveolus (CL+/-A). Subsequently, it was investigated whether further
      morphological grading of incomplete CLs is clinically relevant, and which
      alveolar part is deficient in fusion/differentiation defects. DESIGN:
      Observational cohort study. SETTING: Three hundred fifty adult unoperated
      Indonesian cleft patients presented themselves for operation. Cephalograms,
      dental casts, and intraoral and extraoral photographs-eligible for the present
      study-were used to determine morphological severity of CL+/-A. PATIENTS: Patients
      with unilateral or bilateral clefts of the primary palate only were included.
      MAIN OUTCOME MEASURES: Clefts were classified-according to developmental
      mechanisms and timing in embryogenesis-as fusion and/or differentiation defects.
      Grades of incomplete CLs were related to the severity of alveolar clefts (CAs)
      and hypoplasia, and permanent dentition was used to investigate which alveolar
      part is deficient in fusion/differentiation defects. RESULTS: One hundred eight
      adult patients were included. All subphenotypes-96 unilateral and 12 bilateral
      clefts-could be classified into differentiation (79%), fusion (17%), fusion
      differentiation (2%), or fusion and differentiation (2%) defects. The various
      grades of incomplete CLs were related to associated CAs and hypoplasia, and all
      alveolar deformities were located in the premaxillae. CONCLUSIONS: This study
      showed that all CL+/-A including the Simonart bands can be classified, that
      further morphological grading of incomplete CLs is clinically relevant, and that
      the premaxilla forms the deficient part in alveolar deformities.

PMID- 29652538
TI  - Novel 3-D Analysis for the Assessment of Cleft Dimensions on Digital Models of
      Infants With Unilateral Cleft Lip and Palate.
AB  - OBJECTIVE: To present a 3-D standardized analysis of cleft dimensions. MATERIALS:
      Thirty-one plaster casts of unilateral cleft lip and palate (UCLP) infants were
      laser scanned. Landmarks and coordinate system were defined. Linear distances and
      surfaces were measured, and the ratio between cleft and palatal area was
      calculated (3-D infant cleft severity ratio [3D ICSR]). The digitally measured
      areas were compared with silicone membranes, adapted to the plaster casts, and
      analyzed by optic microscopy. MAIN OUTCOME MEASURES: Repeatability,
      reproducibility, and validity. RESULTS: Bland-Altman plots showed minor bias for
      anterior cleft width (0.16 mm), arch length (0.23 mm), and palatal surface (-9.18
      mm2). The random error was maximum 0.78 mm for linear measurements and 12.1 mm2
      for area measurements, reliability of 3D ICSR was 0.99 (intraclass correlation
      coefficient), differences between measurements on digital and plaster models were
      less than 2%. CONCLUSIONS: The method offers valid and reproducible 3-D
      assessment of cleft size and morphology. 3-D infant cleft severity ratio can be
      used as baseline value for surgical planning and may have a role in predicting
      dentofacial development.

PMID- 29652539
TI  - Maxillary Growth in Cleft Lip and Palate Patients, With and Without Vomerine Flap
      Closure of the Hard Palate at the Time of Lip Repair: A Retrospective Analysis of
      Prospectively Collected Nonrandomized Data, With 10-Year Cephalometric Outcomes.
AB  - OBJECTIVE: To assess the midterm effect on maxillary growth of vomerine flap (VF)
      closure of the hard palate, at the time of lip repair. DESIGN: A retrospective
      analysis of prospectively collected nonrandomized data. INTERVENTIONS:
      Consecutive participants with a unilateral cleft lip and palate (UCLP) were
      operated on, at 3 months of age, by the same surgeon. They were divided into 2
      groups, those who had a VF and those who did not (non-VF). SETTING: Participants
      were treated at 2 hospitals in the United Kingdom. PARTICIPANTS: Twenty-eight
      participants in the VF group and 24 participants in the non-VF group attended
      follow-up at 10 years of age. MAIN OUTCOME MEASURES: Standardized lateral
      cephalometric radiographs were taken at 10 years. Following tracing and
      digitization, parameters to assess the maxillary growth were analyzed. RESULTS:
      No statistically significant differences were found in the anterior-posterior or
      vertical skeletal cephalometric parameters. CONCLUSIONS: The results of this
      study support the statement that VF repair does not significantly affect
      maxillary growth in patients with a UCLP, when assessed cephalometrically at 10
      years of age. It should be noted that at this age, growth is not yet complete.

PMID- 29652540
TI  - MicroRNAs as regulators of mitochondrial dysfunction and obesity.
AB  - Obesity, which has become a major global epidemic, is associated with numerous
      comorbidities and nearly every chronic condition. Mitochondria play a central
      role in this disorder, as they control cell metabolism, regulating important
      processes, such as ATP production, lipid beta-oxidation, oxidative stress, and
      inflammation. MicroRNAs (miRs) have been shown to regulate many biological
      processes associated with obesity, comprising adipocyte differentiation, insulin
      action, and fat metabolism. In addition, recent studies have confirmed that miRs
      are important regulators of mitochondrial function by either directly modulating
      mitochondrial proteins or targeting mitochondrial regulators, thereby modulating
      metabolic process in the context of obesity. In this review, we describe the
      different roles of mitochondria in obesity, specifically in adipose tissue, and
      those miRs that are involved in mitochondrial dysfunction in this disease.

PMID- 29652541
TI  - Dynamic cerebral autoregulation is impaired during submaximal isometric handgrip
      in patients with heart failure.
AB  - The incidence of neurological complications, including stroke and cognitive
      dysfunction, is elevated in patients with heart failure (HF) with reduced
      ejection fraction. We hypothesized that the cerebrovascular response to isometric
      handgrip (iHG) is altered in patients with HF. Adults with HF and healthy
      volunteers were included. Cerebral blood velocity (CBV; transcranial Doppler,
      middle cerebral artery) and arterial blood pressure (BP; Finometer) were
      continuously recorded supine for 6 min, corresponding to 1 min of baseline and 3
      min of iHG exercise, at 30% maximum voluntary contraction, followed by 2 min of
      recovery. The resistance-area product was calculated from the instantaneous BP
      CBV relationship. Dynamic cerebral autoregulation (dCA) was assessed with the
      time-varying autoregulation index estimated from the CBV step response derived by
      an autoregressive moving-average time-domain model. Forty patients with HF and 23
      BP-matched healthy volunteers were studied. Median left ventricular ejection
      fraction was 38.5% (interquartile range: 0.075%) in the HF group. Compared with
      control subjects, patients with HF exhibited lower time-varying autoregulation
      index during iHG, indicating impaired dCA ( P < 0.025). During iHG, there were
      steep rises in CBV, BP, and heart rate in control subjects but with different
      temporal patterns in HF, which, together with the temporal evolution of
      resistance-area product, confirmed the disturbance in dCA in HF. Patients with HF
      were more likely to have impaired dCA during iHG compared with age-matched
      control subjects. Our results also suggest an impairment of myogenic, neurogenic,
      and metabolic control mechanisms in HF. The relationship between impaired dCA and
      neurological complications in patients with HF during exercise deserves further
      investigation. NEW & NOTEWORTHY Our findings provide the first direct evidence
      that cerebral blood flow regulatory mechanisms can be affected in patients with
      heart failure during isometric handgrip exercise. As a consequence, eventual
      blood pressure modulations are buffered less efficiently and metabolic demands
      may not be met during common daily activities. These deficits in cerebral
      autoregulation are compounded by limitations of the systemic response to
      isometric exercise, suggesting that patients with heart failure may be at greater
      risk for cerebral events during exercise.

PMID- 29652542
TI  - Sympathoexcitation constrains vasodilation in the human skeletal muscle
      microvasculature during postocclusive reactive hyperemia.
AB  - We used diffuse correlation spectroscopy to investigate sympathetic
      vasoconstriction, local vasodilation, and integration of these two responses in
      the skeletal muscle microvasculature of 20 healthy volunteers. Diffuse
      correlation spectroscopy probes were placed on the flexor carpi radialis muscle
      or vastus lateralis muscle, and a blood flow index was derived continuously. We
      measured hemodynamic responses during sympathoexcitation induced by forehead
      cooling, after which the effects of the increased sympathetic tone on
      vasodilatory responses during postocclusive reactive hyperemia (PORH) were
      examined. PORH was induced by releasing arterial occlusion (3 min) in an arm or
      leg. To increase sympathetic tone during PORH, forehead cooling was begun 60 s
      before the occlusion release and ended 60 s after the release. During forehead
      cooling, mean arterial pressure rose significantly and was sustained at an
      elevated level. Significant vasoconstriction and decreases in blood flow index
      followed by gradual blunting of the vasoconstriction also occurred. The time
      course of these responses is in good agreement with previous observations in
      animals. The acute sympathoexcitation diminished the peak vasodilation during
      PORH only in the vastus lateralis muscle, but it hastened the decline in
      vasodilation after the peak in both the flexor carpi radialis muscle and vastus
      lateralis muscle. Consequently, the total vasodilatory response assessed as the
      area of the vascular conductance during the first minute of PORH was
      significantly diminished in both regions. We conclude that, in humans, the
      integrated effects of sympathetic vasoconstriction and local vasodilation have an
      important role in vascular regulation and control of perfusion in the skeletal
      muscle microcirculation. NEW & NOTEWORTHY We used diffuse correlation
      spectroscopy to demonstrate that acute sympathoexcitation constrains local
      vasodilation in the human skeletal muscle microvasculature during postocclusive
      reactive hyperemia. This finding indicates that integration of sympathetic
      vasoconstriction and local vasodilation is importantly involved in vascular
      regulation and the control of perfusion of the skeletal muscle microcirculation
      in humans.

PMID- 29652544
TI  - Acute effects of device-guided slow breathing on sympathetic nerve activity and
      baroreflex sensitivity in posttraumatic stress disorder.
AB  - Patients with posttraumatic stress disorder (PTSD) have elevated sympathetic
      nervous system reactivity and impaired sympathetic and cardiovagal baroreflex
      sensitivity (BRS). Device-guided slow breathing (DGB) has been shown to lower
      blood pressure (BP) and sympathetic activity in other patient populations. We
      hypothesized that DGB acutely lowers BP, heart rate (HR), and improves BRS in
      PTSD. In 23 prehypertensive veterans with PTSD, we measured continuous BP, ECG,
      and muscle sympathetic nerve activity (MSNA) at rest and during 15 min of DGB at
      5 breaths/min ( n = 13) or identical sham device breathing at normal rates of 14
      breaths/min (sham; n = 10). Sympathetic and cardiovagal BRS was quantified using
      pharmacological manipulation of BP via the modified Oxford technique at baseline
      and during the last 5 min of DGB or sham. There was a significant reduction in
      systolic BP (by -9 +/- 2 mmHg, P < 0.001), diastolic BP (by -3 +/- 1 mmHg, P =
      0.019), mean arterial pressure (by -4 +/- 1 mmHg, P = 0.002), and MSNA burst
      frequency (by -7.8 +/- 2.1 bursts/min, P = 0.004) with DGB but no significant
      change in HR ( P > 0.05). Within the sham group, there was no significant change
      in diastolic BP, mean arterial pressure, HR, or MSNA burst frequency, but there
      was a small but significant decrease in systolic BP ( P = 0.034) and MSNA burst
      incidence ( P = 0.033). Sympathetic BRS increased significantly in the DGB group
      (-1.08 +/- 0.25 to -2.29 +/- 0.24 bursts.100 heart beats-1.mmHg-1, P = 0.014) but
      decreased in the sham group (-1.58 +/- 0.34 to -0.82 +/- 0.28 bursts.100 heart
      beats-1.mmHg-1, P = 0.025) (time * device, P = 0.001). There was no significant
      difference in the change in cardiovagal BRS between the groups (time * device, P
      = 0.496). DGB acutely lowers BP and MSNA and improves sympathetic but not
      cardiovagal BRS in prehypertensive veterans with PTSD. NEW & NOTEWORTHY
      Posttraumatic stress disorder is characterized by augmented sympathetic
      reactivity, impaired baroreflex sensitivity, and an increased risk for developing
      hypertension and cardiovascular disease. This is the first study to examine the
      potential beneficial effects of device-guided slow breathing on hemodynamics,
      sympathetic activity, and arterial baroreflex sensitivity in prehypertensive
      veterans with posttraumatic stress disorder.

PMID- 29652545
TI  - Keynote lecture: strategies for optimal cardiovascular aging.
AB  - This review summarizes the opening keynote presentation overview of the American
      Physiological Society Conference on Cardiovascular Aging: New Frontiers and Old
      Friends held in Westminster, CO, in August 2017. Age is the primary risk factor
      for cardiovascular diseases (CVDs). Without effective intervention, future
      increases in the number of older adults will translate to a greater prevalence of
      CVDs and related disorders. Advancing age increases the risk of CVDs partly via
      direct effects on the heart and through increases in blood pressure; however,
      much of the risk is mediated by vascular dysfunction, including large elastic
      artery stiffening and both macro- and microvascular endothelial dysfunction.
      Although excessive superoxide-related oxidative stress and chronic low-grade
      inflammation are the major processes driving cardiovascular aging, the upstream
      mechanisms involved represent new frontiers of investigation and potential
      therapeutic targets. Lifestyle practices, including aerobic exercise, energy
      intake (caloric) restriction, and healthy diet composition, are the most evidence
      based strategies (old friends) for optimal cardiovascular aging, but adherence is
      poor in some groups. Healthy lifestyle "mimicking" approaches, including novel
      forms of physical training, intermittent fasting paradigms, exercise/healthy diet
      inspired nutraceuticals (functional foods and natural supplements), as well as
      controlled environmental stress exposure (e.g., heat therapy), may hold promise
      but are unproven. Mitigating the adverse effects of aging on cardiovascular
      function and health is a high biomedical priority.

PMID- 29652543
TI  - Cardioprotection by intermittent hypoxia conditioning: evidence, mechanisms, and
      therapeutic potential.
AB  - The calibrated application of limited-duration, cyclic, moderately intense
      hypoxia-reoxygenation increases cardiac resistance to ischemia-reperfusion
      stress. These intermittent hypoxic conditioning (IHC) programs consistently
      produce striking reductions in myocardial infarction and ventricular
      tachyarrhythmias after coronary artery occlusion and reperfusion and, in many
      cases, improve contractile function and coronary blood flow. These IHC protocols
      are fundamentally different from those used to simulate sleep apnea, a recognized
      cardiovascular risk factor. In clinical studies, IHC improved exercise capacity
      and decreased arrhythmias in patients with coronary artery or pulmonary disease
      and produced robust, persistent, antihypertensive effects in patients with
      essential hypertension. The protection afforded by IHC develops gradually and
      depends on beta-adrenergic, delta-opioidergic, and reactive oxygen-nitrogen
      signaling pathways that use protein kinases and adaptive transcription factors.
      In summary, adaptation to intermittent hypoxia offers a practical, largely
      unrecognized means of protecting myocardium from impending ischemia. The
      myocardial and perhaps broader systemic protection provided by IHC clearly merits
      further evaluation as a discrete intervention and as a potential complement to
      conventional pharmaceutical and surgical interventions.

PMID- 29652546
TI  - Ataxia telangiectasia mutated kinase deficiency impairs the autophagic response
      early during myocardial infarction.
AB  - Ataxia telangiectasia mutated kinase (ATM) is activated in response to DNA
      damage. We have previously shown that ATM plays a critical role in myocyte
      apoptosis and cardiac remodeling after myocardial infarction (MI). Here, we
      tested the hypothesis that ATM deficiency results in autophagic impairment in the
      heart early during MI. MI was induced in wild-type (WT) and ATM heterozygous
      knockout (hKO) mice by ligation of the left anterior descending artery.
      Structural and biochemical parameters of the heart were measured 4 h after left
      anterior descending artery ligation. M-mode echocardiography revealed that MI
      worsens heart function, as evidenced by reduced percent ejection fraction and
      fractional shortening in both groups. However, MI-induced increase in left
      ventricular end-diastolic and end-systolic diameters and volumes were
      significantly lower in hKO hearts. ATM deficiency resulted in autophagic
      impairment during MI, as evidenced by decreased microtubule-associated protein
      light chain 3-II increased p62, decreased cathepsin D protein levels, and
      increased aggresome accumulation. ERK1/2 activation was only observed in WT-MI
      hearts. Activation of Akt and AMP-activated protein kinase (AMPK) was lower,
      whereas activation of glycogen synthase kinase (GSK)-3beta and mammalian target
      of rapamycin (mTOR) was higher in hKO-MI hearts. Inhibition of ATM using KU-55933
      resulted in autophagic impairment in cardiac fibroblasts, as evidenced by
      decreased light chain 3-II protein levels and formation of acidic vesicular
      organelles. This impairment was associated with decreased activation of Akt and
      AMPK but enhanced activation of GSK-3beta and mTOR in KU-55933-treated
      fibroblasts. Thus, ATM deficiency results in autophagic impairment in the heart
      during MI and cardiac fibroblasts. This autophagic impairment may occur via the
      activation of GSK-3beta and mTOR and inactivation of Akt and AMPK. NEW &
      NOTEWORTHY Ataxia telangiectasia mutated kinase (ATM) plays a critical role in
      myocyte apoptosis and cardiac remodeling after myocardial infarction (MI). Here,
      we provide evidence that ATM deficiency results in autophagic impairment during
      MI. Further investigation of the role of ATM in autophagy post-MI may provide
      novel therapeutic targets for patients with ataxia telangiectasia suffering from
      heart disease.

PMID- 29652547
TI  - N-terminal alpha-amino group modification of antibodies using a site-selective
      click chemistry method.
AB  - Site-specific conjugation of small molecules to antibody molecules is a promising
      strategy for generation of antibody-drug conjugates. In this report, we describe
      the successful synthesis of a novel bifunctional molecule, 6-(azidomethyl)-2
      pyridinecarboxyaldehyde (6-AM-2-PCA), which was used for conjugation of small
      molecules to peptides and antibodies. We demonstrated that 6-AM-2-PCA selectively
      reacted with N-terminal amino groups of peptides and antibodies. In addition, the
      azide group of 6-AM-2-PCA enabled copper-free click chemistry coupling with
      dibenzocyclooctyne-containing reagents. Bifunctional 6-AM-2-PCA mediated site
      specific conjugation without requiring genetic engineering of peptides or
      antibodies. A key advantage of 6-AM-2-PCA as a conjugation reagent is its ability
      to modify proteins in a single step under physiological conditions that are
      sufficiently moderate to retain protein function. Therefore, this new click
      chemistry-based method could be a useful complement to other conjugation methods.

PMID- 29652548
TI  - CA125 suppresses amatuximab immune-effector function and elevated serum levels
      are associated with reduced clinical response in first line mesothelioma
      patients.
AB  - The tumor-shed antigen CA125 has recently been found to bind certain monoclonal
      antibodies (mAbs) and suppress immune-effector mediated killing through
      perturbation of the Fc domain with CD16a and CD32a Fc-gamma activating receptors
      on immune-effector cells. Amatuximab is a mAb targeting mesothelin whose
      mechanism of action utilizes in part antibody-dependent cellular cytotoxicity
      (ADCC). It is being tested for its therapeutic activity in patients with
      mesothelioma in combination with first line standard-of-care. To determine if
      CA125 has immunosuppressive effects on amatuximab ADCC and associated clinical
      outcomes, post hoc subgroup analysis of patients from a Phase 2 study with
      primary diagnosed stage III/IV unresectable mesothelioma treated with amatuximab
      plus cisplatin and pemetrexed were conducted. Analysis found patients with
      baseline CA125 levels no greater than 57 U/m (~3X the upper limit of normal) had
      a 2 month improvement in progression free survival (HR = 0.43, p = 0.0062) and a
      7 month improvement in overall survival (HR = 0.40, p = 0.0022) as compared to
      those with CA125 above 57 U/mL. In vitro studies found that CA125 was able to
      bind amatuximab and perturb ADCC activity via decreased Fc-gamma-receptor
      engagement. These data suggest that clinical trial designs of antibody-based
      drugs in cancers producing CA125, including mesothelioma, should consider
      stratifying patients on baseline CA125 levels for mAbs that are experimentally
      determined to be bound by CA125.

PMID- 29652549
TI  - Prolonged granulocyte colony stimulating factor use in glycogen storage disease
      type 1b associated with acute myeloid leukemia and with shortened telomere
      length.
AB  - Glycogen storage disease (GSD) type 1 is a rare autosomal recessive inherited
      condition. The 1b subtype comprises the minority of cases, with an estimated
      prevalence of 1 in 500,000 children. Patients with glycogen storage disease type
      1b are often treated with granulocyte colony stimulating factor (G-CSF) for
      prolonged periods to improve symptoms of inflammatory bowel disease (IBD) and in
      the face of severe neutropenia to decrease risk of infection. Long-term G-CSF
      treatment may result in an increased risk of myelodysplastic syndrome (MDS) or
      acute myeloid leukemia (AML) possibly due to increased marrow stress resulting in
      telomere shortening. To our knowledge, there have been two published cases of AML
      in GSD type 1b patients following long-term G-CSF exposure. Here, we report two
      further cases of AML/MDS-related changes in patients GSD type 1b treated with G
      CSF. One patient developed AML with complex karyotype after 20 years of G-CSF
      treatment. The second patient was found to have short telomeres after 10 years of
      G-CSF exposure, but no evidence of acute leukemia at present. The third patient
      developed AML/MDS after 25 years of G-CSF use, with short telomeres prior to bone
      marrow transplant. Together these cases suggest that GSD type 1b patients with
      prolonged G-CSF exposure may be at an increased risk of MDS/AML states associated
      with G-CSF-induced shortened telomeres. We recommend that any GSD1b patients with
      prolonged G-CSF should have routine telomere assessments with monitoring for MDS
      if telomere shortening is observed, and with particular attention warranted if
      there is unexplained loss of G-CSF responsiveness.

PMID- 29652550
TI  - Chia Seed Supplementation Reduces Senescence Markers in Epididymal Adipose Tissue
      of High-Fat Diet-Fed SAMP8 Mice.
AB  - Adipose tissue is a key organ with substantial senescent cell accumulation under
      both obesity and aging conditions. Chia seed is an ancient seed and is the
      richest plant source of alpha-linolenic acid. We aimed to determine how cellular
      senescence markers will be altered in adipose tissue of senescence-accelerated
      mouse-prone 8 (SAMP8) mice fed with high-fat diets (HFDs); and how chia seed can
      affect the above markers. SAMP8 mice and their control senescence-accelerated
      mouse-resistant 1 (SAMR1) were divided into four groups, that is, SAMR1 low-fat
      diet group (R1LF), SAMP8LF group (P8LF), SAMP8 high-fat group (P8HF), and SAMP8HF
      group supplemented with 10% chia seed (P8HC). At the end of the intervention,
      body composition was measured through T1-weighted magnetic resonance imaging, and
      epididymal (EPI) and subcutaneous (SC) adipose tissues were dissected for further
      analysis. Compared with the R1LF group, the P8HF and P8HC groups had
      significantly increased body fat mass. In EPI fat, p16, CD68 and PAI-1 mRNA
      expression from P8HF group were significantly increased; chia seed partially
      reduced p16 and CD68 mRNA expression. The P8LF group has increased p16 and CD68,
      and the P8HF group has increased p16, p21, and CD68; and P8HC group has increased
      p16 mRNA expression. The protein expression of p-AMPK in EPI and SC fat from the
      P8HF group was reduced. In conclusion, reductions in AMPK activity might be
      partially responsible for elevation in HFD-induced senescence markers in both EPI
      and SC fat, and chia seed supplementation is able to reduce senescence-associated
      markers at least in EPI adipose tissue.

PMID- 29652552
TI  - Do Classes of Polysubstance Use in Adolescence Differentiate Growth in Substances
      Used in the Transition to Young Adulthood?
AB  - BACKGROUND: Past studies have differentiated classes of polysubstance use in
      adolescence, however, the associations of adolescent polysubstance use classes
      with longitudinal substance use trajectories from adolescence to young adulthood
      have not been studied. OBJECTIVE: The current study examined substance use
      classes during adolescence and longitudinal trajectories of each substance used
      across the transition to young adulthood. METHOD: Data were collected biennially
      from 662 youth and followed 10 years across six measurement assessments. Using
      baseline data (T1), latent class analysis was used to identify classes of
      polysubstance use (cigarette, alcohol, marijuana, and illicit drug use) during
      adolescence. Using T2 through T6 data, we fit latent growth models for cigarette,
      alcohol, marijuana, and illicit drug use to examine longitudinal trajectories of
      each substance used by class. RESULTS: A three-class model fit the data best and
      included a poly-use class, that had high probabilities of use among all
      substances, a co-use class, that had high probabilities of use among alcohol and
      marijuana, and a low-use class that had low probabilities of use among all
      substances. We then examined trajectories of each substance used by class. Strong
      continuity of substance use was found by class across 14 years. Additionally, for
      some substances, higher average levels of use of at age 14 were associated with
      change in growth of other substances used over time. Conclusions/Importance:
      Efforts that only target a single drug type may be missing an important
      opportunity to reduce the use and subsequent consequences related to the use of
      multiple substances.

PMID- 29652553
TI  - Mahonia oiwakensis Extract and Its Bioactive Compounds Exert Anti-Inflammatory
      Activities and VEGF Production Through M2-Macrophagic Polarization and STAT6
      Activation.
AB  - Macrophages play an indispensable role in the host immune defense. Macrophages
      can undergo polarization into classically (M1) and alternatively (M2) activated
      macrophages. M1 macrophages activate immune and inflammatory response, while M2
      macrophages are involved in tissue remodeling. Mahonia oiwakensis (Mo) is a
      herbal medicine in Asia used for its anti-inflammatory and analgesic properties;
      however, the mechanism is unclear. This study analyzed the effect of Mo extracts
      and its effects on the polarization of both macrophage RAW264.7 cells and mouse
      splenic macrophages. Water (Mo-W) and EtOH extracts (Mo-E) did not change the
      viability of RAW264.7 cells, whereas Mo-E inhibited nitric oxide (NO) production.
      The major compounds, berberine and palmatine, decreased the viability and NO
      levels of cells. The secretion of inflammatory cytokines CXCL16, IL-6, L
      selectin, MCP1, RANTES, and sTNF-R1 was downregulated, whereas the production of
      vascular endothelial growth factor (VEGF) was upregulated by Mo-E, berberine, and
      palmatine treatments. Mo-E, berberine, and palmatine stimulated the expression of
      macrophage CD68 and M2-type CD204 markers, decreased M1-mediated p-STAT1 and NF
      kappaB, and increased M2-mediated p-STAT6 expression. Similar effects on M2
      polarization were also observed in splenic macrophages from mice. In conclusion,
      Mo-E, berberine, and palmatine modulated macrophages through the suppression of
      M1-mediated inflammation and the recruitment of M2-mediated VEGF secretion and
      STAT6 expression.

PMID- 29652554
TI  - Impact of attention on social functioning in pediatric medulloblastoma survivors.
AB  - BACKGROUND: Parent-reported attention problems have been associated with social
      functioning in a broad sample of pediatric cancer survivors. OBJECTIVE: The
      present study focused on a more homogeneous sample (pediatric medulloblastoma
      survivors), with the novel inclusion of self-reported attention ratings.
      PARTICIPANTS/METHODS: Thirty-three pediatric medulloblastoma survivors, ages 7-18
      years, completed a brief IQ measure and self-report of attentional and social
      functioning. Parents rated patients' attentional and social functioning. RESULTS:
      Mean attention ratings were average based on both parent- and self-report, though
      parent ratings were significantly discrepant from normative means. No significant
      demographic or treatment-related predictors of self-reported attention problems
      were identified, whereas female gender was associated with greater parent
      reported attention problems. Canonical correlation analysis revealed a
      significant association between parent-reported attention difficulties and social
      functioning in pediatric medulloblastoma survivors, but there was no association
      between self-reported attention problems and measures of social functioning.
      CONCLUSIONS: Consistent with existing literature in broader samples of pediatric
      cancer survivors, the present study further affirms attention deficits as an
      underlying contributor to social deficits in pediatric medulloblastoma survivors
      while also finding little relationship between self-reports of attention and
      social performance. Notably, present findings provide additional support
      suggesting that attention functioning is a more significant contributor to social
      outcomes for pediatric medulloblastoma survivors than the level of cognitive
      ability.

PMID- 29652555
TI  - Henry Herbert Donaldson's (1857-1938) contribution to an organized approach to
      the experimental study of the mammalian central nervous system.
AB  - This article shows that the academic and research careers of Henry Herbert
      Donaldson (1857-1938) were directed to provide basic information about the growth
      of the vertebrate nervous system and to provide standards and the means to make
      such research efficient. He earned the reputation of making the albino rat a
      standard laboratory animal. His academic career began when he was an
      undergraduate at Yale University in 1875 and concluded with his death as
      Professor and Head of the Department of Neurology at the Wistar Institute of
      Anatomy and Biology of the University of Pennsylvania in 1938. During that
      period, pivotal experiences occurred, including research in physiological
      chemistry with Chittenden at the Sheffield School at Yale, graduate study at
      Johns Hopkins University, postgraduate study in Europe, and professorial
      positions at Clark University and the University of Chicago. It was at Johns
      Hopkins University that Donaldson learned about the need for physiological,
      anatomical, and psychophysical research and about the techniques to allow such
      research. It was at Clark University that he had first-hand and detailed
      experience with the anatomy of the brain of a deaf-blind-mute woman, as he
      attempted to correlate her sensory deficits with her brain development. It was at
      Clark University that he clearly recognized the need for standardization in
      neurological research. At the University of Chicago, he developed administrative
      skills and began a coordinated research effort to delimit the growth of the
      nervous system. It was at Chicago that he learned that the albino rat could be a
      reasonable subject for such research. It was also at Chicago that he was able to
      formulate ideas about the future organizational needs of human neuroanatomy. It
      was at the Wistar Institute that his research program and his professional career
      matured. He organized a research effort to elucidate the growth of the nervous
      system. He contributed to the coordination of neurological research in the United
      States and Europe. It was while at the Wistar Institute that he became well-known
      for making the albino rat a standard laboratory mammal-a convenient living
      material for research.

PMID- 29652556
TI  - Concordance of Non-Low-Risk Disease Among Pairs of Brothers With Prostate Cancer.
AB  - Purpose Prostate cancer among first-degree relatives is a strong risk factor for
      diagnosis of prostate cancer, and the contribution of heritable factors in
      prostate cancer etiology is high. We investigated how the concordance of non-low
      risk prostate cancer among brothers is affected by their genetic relation.
      Methods We identified 4,262 pairs of brothers with prostate cancer in the
      Prostate Cancer Database Sweden. Their cancers were categorized as low risk
      (Gleason score <= 6; clinical stage T1-2, Nx/N0, Mx/M0; and prostate-specific
      antigen <= 10 ng/mL) or non-low risk. The odds ratio (OR) for concordance of non
      low-risk cancer was calculated with logistic regression for the different types
      of fraternity (monozygotic twins, dizygotic twins, full brothers, and half
      brothers) Results Among monozygotic twins who both were diagnosed with prostate
      cancer, the OR for both brothers being in the non-low-risk category was 3.82 (95%
      CI, 0.99 to 16.72) after adjusting for age and year of diagnosis. Among full
      brothers, the corresponding adjusted OR was 1.21 (95% CI, 1.04 to 1.39). When the
      analysis was restricted to brothers who both were diagnosed within 4 years, the
      results were similar. Conclusion Non-low-risk prostate cancer has a heritable
      pattern suggesting shared genetic factors, with the highest concordance among
      monozygotic twins. Our results suggest that a man whose brother has been
      diagnosed with a non-low-risk prostate cancer is at a clinically relevant
      increased risk of developing an aggressive prostate cancer himself.

PMID- 29652557
TI  - Skeletal response to treatment with teriparatide (TPD) after bisphosphonate in
      post-menopausal women with osteoporosis and a high prevalence of secondary risk
      factors in real-life setting of a metabolic bone clinic; effect of age and
      vitamin D status.
AB  - PURPOSE: Teriparatide (TPD) is a skeletal anabolic agent used in patients with
      severe post-menopausal osteoporosis (PMO) and steroid-induced osteoporosis who
      are at hish risk of fracture. Predictors of therapeutic response to teriparatide
      in real-life setting are not well characterised. We investigated potential
      factors associated with teriparatide response in post-menopausal women with
      established osteoporosis. METHODS: We carried out a retrospective survey of 48
      women, aged 73.2 [7.5] years with severe osteoporosis and prevalent fractures
      treated with TPD according to the NICE criteria. BMD was measured at baseline, 6
      12 and 18-24 months at the lumbar spine (LS), total hip (TH) and femoral neck
      (FN). Bone turnover markers, serum 25 (OH)vitamin D were determined at 3-12 and
      12-24 months. RESULTS: BMD increased at 6-12 months (% change mean [SEM] 6.5
      [1.1] p = 0.004) and 18-24 months (8.45 % [1.2] p<0.001) at the LS. A significant
      increase in BMD was observed at FN (3.1 [1.3] % p = 0.02). Changes in BMD at the
      TH was higher in patients younger than 73 years compared to older women (% change
      in BMD 4.13 [1.64] % v/s -1.7 [1.1] p = 0.007). Baseline 25 (OH) vitamin D
      correlated with change in P1NP at 3-12 months (r = 0.45 p = 0.049). CONCLUSIONS:
      TPD-induced changes in BMD at the TH appears may be dependent on age. Vitamin D
      status may influence the early anabolic effect to TPD. Our data suggest that
      these factors may be important considerations when initiating and optimising
      treatment with TPD, although further larger studies are needed to confirm these
      findings.

PMID- 29652551
TI  - n-3 Fatty Acid Supplementation for the Treatment of Dry Eye Disease.
AB  - BACKGROUND: Dry eye disease is a common chronic condition that is characterized
      by ocular discomfort and visual disturbances that decrease quality of life. Many
      clinicians recommend the use of supplements of n-3 fatty acids (often called
      omega-3 fatty acids) to relieve symptoms. METHODS: In a multicenter, double-blind
      clinical trial, we randomly assigned patients with moderate-to-severe dry eye
      disease to receive a daily oral dose of 3000 mg of fish-derived n-3
      eicosapentaenoic and docosahexaenoic acids (active supplement group) or an olive
      oil placebo (placebo group). The primary outcome was the mean change from
      baseline in the score on the Ocular Surface Disease Index (OSDI; scores range
      from 0 to 100, with higher scores indicating greater symptom severity), which was
      based on the mean of scores obtained at 6 and 12 months. Secondary outcomes
      included mean changes per eye in the conjunctival staining score (ranging from 0
      to 6) and the corneal staining score (ranging from 0 to 15), with higher scores
      indicating more severe damage to the ocular surface, as well as mean changes in
      the tear break-up time (seconds between a blink and gaps in the tear film) and
      the result on Schirmer's test (length of wetting of paper strips placed on the
      lower eyelid), with lower values indicating more severe signs. RESULTS: A total
      of 349 patients were assigned to the active supplement group and 186 to the
      placebo group; the primary analysis included 329 and 170 patients, respectively.
      The mean change in the OSDI score was not significantly different between the
      active supplement group and the placebo group (-13.9 points and -12.5 points,
      respectively; mean difference in change after imputation of missing data, -1.9
      points; 95% confidence interval [CI], -5.0 to 1.1; P=0.21). This result was
      consistent across prespecified subgroups. There were no significant differences
      between the active supplement group and the placebo group in mean changes from
      baseline in the conjunctival staining score (mean difference in change, 0.0
      points; 95% CI, -0.2 to 0.1), corneal staining score (0.1 point; 95% CI, -0.2 to
      0.4), tear break-up time (0.2 seconds; 95% CI, -0.1 to 0.5), and result on
      Schirmer's test (0.0 mm; 95% CI, -0.8 to 0.9). At 12 months, the rate of
      adherence to treatment in the active supplement group was 85.2%, according to the
      level of n-3 fatty acids in red cells. Rates of adverse events were similar in
      the two trial groups. CONCLUSIONS: Among patients with dry eye disease, those who
      were randomly assigned to receive supplements containing 3000 mg of n-3 fatty
      acids for 12 months did not have significantly better outcomes than those who
      were assigned to receive placebo. (Funded by the National Eye Institute, National
      Institutes of Health; DREAM ClinicalTrials.gov number, NCT02128763 .).

PMID- 29652558
TI  - A High-Resolution Digital DNA Melting Platform for Robust Sequence Profiling and
      Enhanced Genotype Discrimination.
AB  - DNA melting analysis provides a rapid method for genotyping a target amplicon
      directly after PCR amplification. To transform melt genotyping into a broad-based
      profiling approach for heterogeneous samples, we previously proposed the
      integration of universal PCR and melt analysis with digital PCR. Here, we
      advanced this concept by developing a high-resolution digital melt platform with
      precise thermal control to accomplish reliable, high-throughput heat ramping of
      microfluidic chip digital PCR reactions. Using synthetic DNA oligos with defined
      melting temperatures, we characterized sources of melting variability and
      minimized run-to-run variations. Within-run comparisons throughout a 20,000
      reaction chip revealed that high-melting-temperature sequences were significantly
      less prone to melt variation. Further optimization using bacterial 16S amplicons
      revealed a strong dependence of the number of melting transitions on the heating
      rate during curve generation. These studies show that reliable high-resolution
      melt curve genotyping can be achieved in digital, picoliter-scale reactions and
      demonstrate that rate-dependent melt signatures may be useful for enhancing
      automated melt genotyping.

PMID- 29652559
TI  - Point prevalence survey of antibiotic use and resistance at a referral hospital
      in Kenya: findings and implications.
AB  - BACKGROUND AND AIMS: A substantial amount of antibiotic use in hospitals may be
      inappropriate, potentially leading to the development and spread of antibiotic
      resistance, adverse effects, mortality and increased hospital costs. The
      objective was to assess current patterns of antibiotic use in a leading referral
      hospital in Western Kenya. This would lead to the identification of opportunities
      for quality improvement in this hospital and others across Kenya. METHODOLOGY: A
      point prevalence survey was carried out with data abstracted principally from
      patient medical records supplemented by interviews from physicians when needed.
      The pattern of antibiotic use was analyzed by descriptive methods. Differences in
      antibiotic use and indications between the selected wards were compared using the
      Chi-square test or Fisher's exact tests. RESULTS: Among the patients surveyed,
      67.7% were on antibiotics. The most common classes of antibiotics prescribed were
      third generation cephalosporins (55%), imidazole derivatives like metronidazole
      (41.8%) and broad spectrum penicillins (41.8%). The most common indication for
      antibiotic use was medical prophylaxis (29%), with local guidelines advocating
      antibiotic prophylaxis in mothers after delivery of their child as well as in
      neonates with birth asphyxia and low weight at birth. Dosing of antibiotics was
      seen as generally optimal when assessed against current recommendations.
      CONCLUSION: Whilst the dosing of antibiotics seemed adequate, there was high use
      of antibiotics in this hospital. This needs to be urgently reviewed with
      currently appreciable empiric antibiotic use. Programmes are being instigated to
      address these concerns. This includes developing antibiotic guidelines and
      formularies especially for empiric use as well as implementing antimicrobial
      stewardship activities.

PMID- 29652560
TI  - Drinking Goal Trajectories and Their Association with Client Characteristics and
      Outcomes among Clients in Outpatient Alcohol Treatment.
AB  - BACKGROUND: Drinking goal preferences could change over time in alcohol treatment
      and during follow up. OBJECTIVES: To examine the stability of drinking goals over
      time, types of drinking goal trajectory, and the associations between drinking
      goal trajectories and baseline client characteristics and treatment outcomes.
      METHODS: We performed secondary analysis of a dataset from a multicenter
      longitudinal study on the effectiveness of outpatient alcohol treatment (n =
      543). Drinking goals (abstinence, controlled drinking, nonrestricted drinking,
      undecided) and alcohol use were assessed at treatment admission, discharge, and 6
      and 12-month follow up. RESULTS: At admission, 32% of the subjects aimed for
      abstinence and 57% for controlled drinking, while 10% were undecided, and 1% did
      not want to restrict themselves. The proportions of clients aiming for abstinence
      and controlled drinking were relatively stable across the four assessments, and
      the proportion of clients who changed their drinking goal from abstinence to
      controlled drinking did not differ significantly from the number who changed in
      the opposite direction. Clients with abstinence-focused trajectories reported
      higher baseline alcohol use than those focused primarily on controlled drinking.
      Meanwhile, attaining nonhazardous drinking and reduced alcohol use at 12-month
      follow up were more likely among clients with abstinence-focused trajectories
      than those focused on controlled drinking. CONCLUSIONS: Since the majority of
      clients maintain their initially selected drinking goal, counsellors might inform
      them at treatment admission about the various probabilities of achieving
      nonhazardous drinking depending on their selected drinking goal.

PMID- 29652561
TI  - Treatment of metastatic hepatocellular carcinoma in pediatric patients: Two case
      reports.

PMID- 29652562
TI  - Serious gaming: A tool to educate health care providers about domestic violence.
AB  - Due to many adverse health effects, victims of domestic violence are frequently
      seen in the health care system. Yet, health care providers may lack the training
      to assist them. Online curricula can be an effective instructional tool. Our
      competency-based, serious video game, Responding to Domestic Violence in Clinical
      Settings, was designed to address health care providers' knowledge gaps through
      17 modules, each a half hour in length. Nearly 9,000 participants completed at
      least one module; nursing students completed the most modules, approximately five
      hours of instruction. This serious video game-based curriculum is useful in
      helping health providers and students learn about Domestic Violence.

PMID- 29652563
TI  - The Impact of Recreational Marijuana Legislation in Washington, DC on Marijuana
      Use Cognitions.
AB  - BACKGROUND: There is little published research that tests the effect of
      recreational marijuana legislation on risk-related cognitions and how individuals
      respond immediately after legislative approval. OBJECTIVES: The objective was to
      test whether learning about the passage of Initiative 71, a voter referendum that
      legalized recreational use of marijuana in the District of Columbia, would lead
      individuals to adopt more favorable marijuana cognitions than they had before the
      Initiative was passed. METHODS: Undergraduate students (N = 402) completed two
      web-based questionnaires in 2014. The first questionnaire was completed prior to
      the referendum vote and the follow-up questionnaire was completed after voters
      approved Initiative 71. Attitudes, perceived norms, intentions, prototypes, and
      willingness were measured at time 1 and time 2. Study hypotheses were tested
      using repeated-measures analysis of covariance. RESULTS: Results showed that
      attitudes, intentions, perceived norms, and willingness to use marijuana were
      more favorable after Initiative 71 was passed. However, the increase in attitudes
      and willingness was moderated by past experience with marijuana whereby the
      increases were statistically significant only among those with the least
      experience. The increase in perceived norms was also moderated by past experience
      whereby increases were statistically significant among those who were moderate or
      heavy users. The passage of Initiative 71 had no effect on favorable prototypes.
      Conclusion/Importance: Legalization may have the unintended outcome of leading to
      more favorable intentions to use marijuana and might lead abstainers or
      experimental users to become more frequent users of marijuana via more positive
      attitudes and willingness towards marijuana use.

PMID- 29652564
TI  - Examining the Relationship Between Nonalcoholic Fatty Liver Disease and the
      Metabolic Syndrome in Nondiabetic Subjects.
AB  - OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) is considered by some to be
      the hepatic manifestation of the metabolic syndrome (MS). However, others believe
      NAFLD is a distinct entity that actually initiates MS. Whichever is true, a
      definite linkage exists between both is generally accepted based upon the
      frequency of common occurrence and realization that insulin resistance (IR) is
      and realization that. The objective is to better understand the relationship
      between NAFLD and MS. Specifically, is there any concrete evidence that
      development of NAFLD precedes MS or vice versa? Another goal was to better
      comprehend capabilities of circulating aminotransferases (aspartate
      aminotransferase [AST] and alanine aminotransferase [ALT]) and their ratio used
      commonly for diagnosis of NAFLD. METHODS: Data from 288 participants with fasting
      blood glucose (FBG) levels below the diabetic level (<125 mg/dL) and AST and ALT
      values in the normal range (<40 U/L) were examined. Correlations between ALT and
      AST and their ratio as independent variables with a variety of metabolic
      parameter were evaluated and compared. RESULTS: Like FBG, many significant
      positive correlations among glucose-insulin indices, body composition, blood
      pressure, dyslipidemias, and inflammation were discovered using ALT, and less so
      with AST, as the independent variable. In some cases, even stronger correlations
      in a negative direction with IR and MS were found with the ratio AST/ALT.
      Corroboration occurred when values in the lowest and highest quartiles of ALT and
      AST/ALT readings showed appropriate statistically significant differences.
      CONCLUSIONS: The findings here suggest that both NAFLD and the MS very early in
      development have a common inciting mechanism(s)-most likely IR. Accordingly, the
      early concurrent temporal results are consistent with the concept that NAFLD is a
      hepatic manifestation of the IR associated with the MS. They do not exclude the
      possibility that once some liver functional adjustments take place, several
      aspects of the MS are bolstered further, perhaps via intensified heightening of
      IR.

PMID- 29652567
TI  - A Khorasan Wheat-Based Replacement Diet Improves Risk Profile of Patients With
      Nonalcoholic Fatty Liver Disease (NAFLD): A Randomized Clinical Trial.
AB  - OBJECTIVE: KAMUT khorasan is an ancient grain with widely acclaimed health
      benefits. The aim of this study was to investigate the effects of a replacement
      diet with ancient khorasan wheat products in patients with NAFLD, in comparison
      to a similar replacement diet with control products made from organic semi-whole
      grain modern wheat. METHODS: Forty NAFLD patients (12 M/28 F; age 55.2 +/- 10.4
      years) with mild to moderate liver steatosis were included. The experimental
      design was a randomized, double-blind, parallel-arm study with 20 participants
      assigned to consume either KAMUT khorasan or control wheat products (pasta,
      bread, crackers, biscuits) over a 3-month period. Anthropometric measurements,
      blood analyses, and ultrasonography examination were performed at both the
      beginning and end of each dietary intervention. RESULTS: After the implementation
      of a general linear model for repeated measurements adjusted for baseline
      demographic details, risk factors, and medication, alanine aminotransferase (ALT)
      was significantly reduced by 12%, aspartate aminotransferase (AST) by 14%,
      alkaline phosphatase (ALP) by 8%, and cholesterol by 6% only in the khorasan
      group (p < 0.05 for all). Similarly, significant reductions in circulating
      proinflammatory tumor necrosis factor-alpha by 50%, interleukin l-receptor
      antagonist-alpha by 37%, interleukin-8 by 24%, and interferon gamma by 24% were
      evident only in participants who consumed the khorasan products (p < 0.05 for
      all). Finally, significant improvements in the liver steatosis grading, Doppler
      perfusion index values, and reactive oxygen species (ROS) production were evident
      after consumption of both the khorasan and control products. CONCLUSIONS: This
      study suggests that a short-term replacement diet with ancient KAMUT khorasan
      products is most effective in reducing metabolic risk factors and ameliorating
      the liver profile in patients with NAFLD.

PMID- 29652568
TI  - Photons Harmony for Cell Communication.

PMID- 29652569
TI  - Efficacy of Various Pretreatments on the Bond Strength of Denture Teeth to
      Denture Base Resins.
AB  - OBJECTIVE: This in vitro study evaluated the shear bond strength (SBS) of heat
      cured denture base resin (PMMA) to acrylic resin teeth treated with different
      pretreatments, especially laser irradiation of different powers (1-4 W).
      MATERIALS AND METHODS: The acrylic resin teeth were separated into seven groups
      (n = 10) for the following different pretreatments: control group (no surface
      treatment) (G1), grinding with a tungsten carbide bur (G2), sandblasting (G3),
      and erbium, chromium: yttrium, scandium, gallium, garnet (Er,Cr:YSGG) laser
      irradiation at 1 W, 2 W, 3 W, 4 W output powers in (G4-7), respectively. Test
      specimens were produced according to the PMMA manufacturers' instructions and
      were subjected to a SBS test at a crosshead speed of 1 mm/min until fracture.
      Debonded surfaces were evaluated by a stereomicroscope for the type of failure.
      SEM (scanning electron microscope) analyses were done to estimate the surface
      changes of the acrylic resin teeth. The data were submitted using a one-way ANOVA
      and post hoc Tukey-Kramer multiple comparison tests (p = 0.05). RESULTS: The
      highest bond strength was obtained in G3, and similar SBS values were considered
      in other groups, and no significant differences were found among the surface
      treatments and the control group (p < 0.05). All groups had a high percentage of
      adhesive failures. CONCLUSIONS: Laser irradiations promote surface topography
      alterations. However laser irradiation of the adhesive surface was found
      ineffective. The SBS of acrylic resin teeth to a PMMA denture base material is
      independent of the surface pretreatments Er,Cr:YSGG laser irradiation,
      sandblasting, and grinding with a carbide bur. All the surface treatments
      provided a similar bond between the acrylic denture base and the teeth.

PMID- 29652570
TI  - Shear Bond Strength of Composite and Ceromer Superstructures to Direct Laser
      Sintered and Ni-Cr-Based Infrastructures Treated with KTP, Nd:YAG, and Er:YAG
      Lasers: An Experimental Study.
AB  - OBJECTIVE: The aim of this study was to examine the shear bond strength (SBS) of
      ceromer and nanohybrid composite to direct laser sintered (DLS) Cr-Co and Ni-Cr
      based metal infrastructures treated with erbium-doped yttrium aluminum garnet
      (Er:YAG), neodymium-doped yttrium aluminum garnet (Nd:YAG), and potassium titanyl
      phosphate (KTP) laser modalities in in vitro settings. METHODS: Experimental
      specimens had four sets (n = 32) including two DLS infrastructures with ceromer
      and nanohybrid composite superstructures and two Ni-Cr-based infrastructures with
      ceromer and nanohybrid composite superstructures. Of each infrastructure set, the
      specimens randomized into four treatment modalities (n = 8): no treatment
      (controls) and Er:YAG, Nd:YAG, and KTP lasers. The infrastructures were prepared
      in the final dimensions of 7 * 3 mm. Ceromer and nanohybrid composite was applied
      to the infrastructures after their surface treatments according to randomization.
      The SBS of specimens was measured to test the efficacy of surface treatments.
      Representative scanning electron microscopy (SEM) images after laser treatments
      were obtained. RESULTS: Overall, in current experimental settings, Nd:YAG, KTP,
      and Er:YAG lasers, in order of efficacy, are effective to improve the bonding of
      ceromer and nanohybrid composite to the DLS and Ni-Cr-based infrastructures (p <
      0.05). Nd:YAG laser is more effective in the DLS/ceromer infrastructures (p <
      0.05). KTP laser, as second more effective preparation, is more effective in the
      DLS/ceromer infrastructures (p < 0.05). SEM findings presented moderate
      accordance with these findings. CONCLUSIONS: The results of this study supported
      the bonding of ceromer and nanohybrid composite superstructures to the DLS and Ni
      Cr-based infrastructures suggesting that laser modalities, in order of success,
      Nd:YAG, KTP, and Er:YAG, are effective to increase bonding of these structures.

PMID- 29652572
TI  - Interview with Prof. Ramy K. Aziz, Cairo University. The Dawn of
      Pharmacomicrobiomics.

PMID- 29652571
TI  - Hemolasertherapy: A Novel Procedure for Gingival Papilla Regeneration-Case
      Report.
AB  - BACKGROUND: Interdental papilla is of major importance to patients' orofacial
      aesthetics, especially regarding anterior teeth as part of the smile's harmony.
      Loss of gingival tissue, which constitutes interdental papilla, forms what in
      odontology is called black spaces. This loss, besides affecting the smile's
      aesthetics, also provokes phonetic and functional damage. OBJECTIVE: The
      objective of the authors is to present the result of three clinical cases treated
      with an innovative technique called hemolasertherapy, which stimulates growth of
      gingival papilla and thus permanently fills in the black spaces. METHODS: The
      photobiomodulation therapy (PBMT) used a 660 nm diode laser (Laser Duo, MMO-Sao
      Carlos, SP, Brazil), punctual, contact mode in two steps: before the bleeding
      (first PBMT) and immediately after bleeding (second PBMT). Parameters used were
      power output: 100 mW, CW; diameter tip: 5 mm; spot area: 0.19 cm2; irradiation
      exposure time per point: 20 sec; 14 points per daily session; total of 2
      sessions, with a 1-week interval; E: 2 J per point; E: per daily session, 28 J;
      irradiance per point: 0.52 W/cm2; fluence per point: 10.4 J/cm2. Total in two
      daily sessions: total energy: 56 J; total fluence: 294.75 J/cm, 560 sec total
      time. An in vitro preliminary study was simultaneously carried out to demonstrate
      what could happen at cellular level in hemotherapy clinical cases associated with
      PBMT laser application. RESULTS: This initial study demonstrated that the blood
      clot originated from the bleeding provoked in the gingival area is rich in
      mesenchymal stem cells. PBMT enables preservation, viability, and further
      differentiation, stimulating the return of gingival stem cells, which would
      support their survival and differentiation in the blood clot, thus favoring
      interdental papilla regeneration. CONCLUSIONS: Follow-up was done for a time span
      of 4-5 years and considered excellent with regard to papilla preservation.

PMID- 29652573
TI  - Quantitative Assessment of Shotgun Metagenomics and 16S rDNA Amplicon Sequencing
      in the Study of Human Gut Microbiome.
AB  - The analysis of microbiota composition in humans, animals, and built environments
      is important because of emerging roles and applications in a broad range of
      disease and ecological phenotypes. Next Generation Sequencing is the current
      method of choice to characterize microbial community composition. The taxonomic
      profile of a microbial community can be obtained either by shotgun analysis of
      random DNA fragments or through 16S ribosomal RNA gene (rDNA) amplicon
      sequencing. It has been previously shown that the 16S rDNA amplicon sequencing
      approach yields quantitatively and qualitatively different results compared to
      shotgun metagenomics when the two techniques are used to assess microbial
      community composition on the same samples. However, most of such comparisons were
      either based on the recovery of 16S rDNA sequences in the shotgun metagenomics
      data or limited to a single microbiome or synthetic samples. Direct comparison of
      shotgun metagenomics and 16S rDNA amplicon sequencing on the same samples was
      performed only once in the recent literature, suggesting that the two methods
      yield comparable results. Here, we set out to compare the outcome of these two
      alternative approaches to the microbiome characterization in human gut
      microbiomes from stool samples. To this end, we processed six different samples
      with both techniques. We report here that shotgun next generation sequencing
      metagenomics allows much deeper characterization of the microbiome complexity,
      allowing identification of a larger number of species for each sample, compared
      to 16S rDNA amplicon sequencing. Further comparative studies in independent
      samples are called for.

PMID- 29652574
TI  - Transcriptomic Biomarkers for Huntington's Disease: Are Gene Expression
      Signatures in Whole Blood Reliable Biomarkers?
AB  - Huntington's disease (HD) is a severe neurodegenerative disorder manifesting as
      progressive impairment of motor function, cognitive decline, psychiatric
      symptoms, and immunological and endocrine dysfunction. We explored the
      consistency of blood transcriptomic biomarkers in HD based on a novel Slovene
      patient cohort and expert review of previous studies. HumanHT-12 v4 BeadChip
      microarrays were performed on the whole blood samples of a cohort of 23 HD
      mutation carriers and 23 controls to identify differentially expressed (DE)
      transcripts. In addition, we performed an expert review of DE transcripts
      identified in comparable HD studies from whole blood, to identify any consistent
      signature of HD. In the Slovene cohort, we identified 740 DE transcripts (p <
      0.01 and a false discovery rate (FDR) of <0.1) of which 414 were downregulated
      and 326 were upregulated. Pathway analyses of DE transcripts showed enrichment
      for pathways involved in systemic, rather than neural processes in HD. With an
      expert review of comparable studies, we have further identified 15 DE transcripts
      shared by 3 studies. We suggest transcriptomic changes in blood reflect systemic
      changes in HD pathogenesis, rather than being a direct result of the
      neuropathological processes in the central nervous system during HD progression,
      and thus, have limited value as disease biomarkers.

PMID- 29652575
TI  - Olive Fruit Blends Modulate Lipid-Sensing Nuclear Receptor PPARgamma, Cell
      Survival, and Oxidative Stress Response in Human Osteoblast Cells.
AB  - OBJECTIVE: The aim of the present study was to investigate how different
      extravirgin olive oils (EVOOs), obtained by blending Olea europea cultivars,
      could influence the cell growth, the response to inflammatory stimuli, and
      oxidative stress in a culture of the osteosarcoma cell line Saos-2. METHODS:
      Three different extravirgin olive oils were physicochemically characterized,
      determining the free acidity, the oxidation status, the polyphenols content, and
      the antioxidative activity. Moreover, the effects on Saos-2 cell culture were
      determined, studying the mRNA expression level by real-time polymerase chain
      reaction (PCR) assays and the antioxidative activity using fluorescent probes.
      RESULTS: The cultivars used in the south of Italy, yield extravirgin oils with
      different amount of fatty acids and polyphenols, which counteract induction of
      proinflammatory cytokines and regulate free radical production in hydrogen
      peroxide-stimulated cells. In vitro analysis using the human osteoblast cell line
      Saos-2 showed that the addition of oils to cell culture simulated a hypoxic
      stress followed by a reoxygenation period, during which the antioxidant activity
      of extravirgin olive oils protected cells from oxidative damages. On the other
      hand, the mRNA expression levels of factors involved in inflammatory processes,
      cell growth recovery, and antioxidant response, as heme oxygenase-1, were
      differently stimulated by EVOOs. Moreover, peroxisome proliferator activated
      receptor gamma (PPARgamma) was differently modulated by EVOOs. CONCLUSION: These
      findings show that the blending of different extravirgin olive oil can impact an
      osteoblast cell line, in particular regarding cell growth recovery and oxidative
      stress.

PMID- 29652576
TI  - Influence of Avocado Puree as a Fat Replacer on Nutritional, Fatty Acid, and
      Organoleptic Properties of Low-Fat Muffins.
AB  - OBJECTIVE: The feasibility of developing reduced-fat muffins with avocado is
      investigated by preparing muffins with 25%, 50%, 75%, and 100% avocado puree as a
      fat (butter) replacer. METHODOLOGY: The resulting products were compared to the
      control muffin, which was made with 100% butter. Muffins were analyzed for
      nutritional content, fatty acid profiles, and sensory acceptability. RESULT:
      Muffins incorporated with avocado puree revealed a significant increase (p <
      0.05) with respect to moisture, ash, and carbohydrate in comparison with the
      control sample. However, no significant changes (p > 0.05) were detected in all
      muffin formulations for protein and dietary fiber content. Both fat content and
      caloric value of muffins incorporated with avocado puree were significantly
      decreased (p < 0.05). The fatty acid profile showed that there was an increment
      in the monounsaturated fatty acids (MUFA) content by 16.51% at full-fat
      substitution. The sensory evaluation test demonstrated that muffins had
      acceptability at up to 50% substitution. Fat substitution at higher than 50% lead
      to undesirable flavor and aftertaste, which was significant (p < 0.05) to the
      panelists. CONCLUSION: The findings indicated the feasibility of avocado puree in
      fat-reduced muffin preparation with an optimal level of 50% avocado puree
      substitution.

PMID- 29652577
TI  - Lung Cancers Associated with Cystic Airspaces: Underrecognized Features of Early
      Disease.
AB  - Early lung cancers associated with cystic airspaces are increasingly being
      recognized as a cause of delayed diagnoses-owing to data gathered from screening
      trials and encounters in routine clinical practice as more patients undergo
      serial imaging. Several morphologic subtypes of cancers associated with cystic
      airspaces exist and can exhibit variable patterns of progression as the solid
      elements of the tumor grow. Current understanding of the pathogenesis of these
      malignancies is limited, and the numbers of cases reported in the literature are
      small. However, several tumor cell types are represented in these lesions, with
      adenocarcinoma predominating. The features of cystic airspaces differ among cases
      and include emphysematous bullae, congenital or fibrotic cysts, subpleural blebs,
      bronchiectatic airways, and distended distal airspaces. Once identified, these
      cystic lesions pose management challenges to radiologists in terms of
      distinguishing them from benign mimics of cancer that are commonly seen in
      patients who also are at increased risk of lung cancer. Rendering a definitive
      tissue-based diagnosis can be difficult when the lesions are small, and affected
      patients tend to be in groups that are at higher risk of requiring biopsy or
      resection. In addition, the decision to monitor these cases can add to patient
      anxiety and cause the additional burden of strained departmental resources. The
      authors have drawn from their experience, emerging evidence from international
      lung cancer screening trials, and large databases of lung cancer cases from other
      groups to analyze the prevalence and evolution of lung cancers associated with
      cystic airspaces and provide guidance for managing these lesions. Although there
      are insufficient data to support specific management guidelines similar to those
      for managing small solid and ground-glass lung nodules, these data and guidelines
      should be the direction for ongoing research on early detection of lung cancer.
      (c)RSNA, 2018.

PMID- 29652578
TI  - MR Imaging of the Fetal Face: Comprehensive Review.
AB  - The human face is a complex anatomic structure with an equally complex
      embryologic development. Derangement of the developmental process can result in
      various structural anomalies, which range from a mainly cosmetic deformity, such
      as cleft lip, to potentially life-threatening conditions such as arhinia. These
      anomalies (a) can occur as isolated anomalies; (b) can be associated with
      intracranial, spinal, or dental anomalies; or (c) can be a part of various
      syndromes, thus serving as diagnostic clues in such cases. Proper evaluation of
      fetal facial deformities can help in prognostication, family counseling, and
      prenatal or early postnatal intervention. Ultrasonography (US) is the first line
      of investigation in these cases. However, when US does not allow complete
      evaluation of these anomalies owing to its inherent limitations, magnetic
      resonance (MR) imaging allows comprehensive evaluation of the anomaly itself and
      also evaluation of various associations and the treatment approach. The
      embryology of the fetal facial structures is considered with regard to the MR
      imaging technique and the MR imaging anatomy. The MR imaging features of various
      structural anomalies are described and classified into six groups, namely,
      orofacial clefts, orbital anomalies, nasal anomalies, facial masses, external ear
      anomalies, and abnormal face shape or profile. Also, the key associations and
      relevant treatment implications are reviewed. The article provides a "one-stop
      shop" review of these unique disorders-from basic understanding of the embryology
      to applying the knowledge in clinical practice, helping the interprofessional
      team and the patients alike. (c)RSNA, 2018.

PMID- 29652579
TI  - Assessment of the Contribution of Dietary and Beverage Intake Quality to Obesity
      Development.
AB  - OBJECTIVE: Low dietary quality is an important indicator of unhealthy eating
      patterns that can lead to some consequences such as obesity, so policy is a very
      powerful tool that can affect the consumption of both healthy and unhealthy
      foods. Indices that assess whether nutritional policies are applied contribute to
      the assessment of the quality of the population's diet. This study was conducted
      to investigate the quality of diets and beverages consumed by Turkish adults, and
      the factors affecting them. METHOD: This cross-sectional descriptive study was
      conducted on 352 adults aged between 18 and 58 years. The quality of diet and
      beverage was measured through the Healthy Eating Index-2010 (HEI) and Healthy
      Beverage Index (HBI), respectively, using 2-day (weekday and weekend) dietary
      recall data. RESULTS: The total HBI scores were 79.1 +/- 11.8 and 81.0 +/- 11.6;
      total HEI-2010 scores were 45.9 +/- 12.3 and 52.3 +/- 11.0, of men and women,
      respectively (p < 0.05). The women had significantly higher scores than that of
      the men in the HEI-2010 subcomponent of empty calories (p > 0.05). Sugar
      sweetened beverage (HBI subcomponent) was significantly correlated with the
      scores of HEI-2010 and empty calorie (HEI-2010 subcomponent), as expected (p <
      0.01). The caloric beverages contributed ~133.6 kcal/d to the total caloric
      intake. CONCLUSIONS: The mean contribution of beverages to total daily energy
      intake of participants was found to be at the suggestion level. This result is
      rewarding when the relationship of sugar-sweetened beverages scores with the
      scores of HEI and empty calories is considered.

PMID- 29652580
TI  - Methods for Assessment of Memory Reactivation.
AB  - It has been suggested that reactivation of previously acquired experiences or
      stored information in declarative memories in the hippocampus and neocortex
      contributes to memory consolidation and learning. Understanding memory
      consolidation depends crucially on the development of robust statistical methods
      for assessing memory reactivation. To date, several statistical methods have seen
      established for assessing memory reactivation based on bursts of ensemble neural
      spike activity during offline states. Using population-decoding methods, we
      propose a new statistical metric, the weighted distance correlation, to assess
      hippocampal memory reactivation (i.e., spatial memory replay) during quiet
      wakefulness and slow-wave sleep. The new metric can be combined with an
      unsupervised population decoding analysis, which is invariant to latent state
      labeling and allows us to detect statistical dependency beyond linearity in
      memory traces. We validate the new metric using two rat hippocampal recordings in
      spatial navigation tasks. Our proposed analysis framework may have a broader
      impact on assessing memory reactivations in other brain regions under different
      behavioral tasks.

PMID- 29652581
TI  - A Learning Framework for Winner-Take-All Networks with Stochastic Synapses.
AB  - Many recent generative models make use of neural networks to transform the
      probability distribution of a simple low-dimensional noise process into the
      complex distribution of the data. This raises the question of whether biological
      networks operate along similar principles to implement a probabilistic model of
      the environment through transformations of intrinsic noise processes. The
      intrinsic neural and synaptic noise processes in biological networks, however,
      are quite different from the noise processes used in current abstract generative
      networks. This, together with the discrete nature of spikes and local circuit
      interactions among the neurons, raises several difficulties when using recent
      generative modeling frameworks to train biologically motivated models. In this
      letter, we show that a biologically motivated model based on multilayer winner
      take-all circuits and stochastic synapses admits an approximate analytical
      description. This allows us to use the proposed networks in a variational
      learning setting where stochastic backpropagation is used to optimize a lower
      bound on the data log likelihood, thereby learning a generative model of the
      data. We illustrate the generality of the proposed networks and learning
      technique by using them in a structured output prediction task and a
      semisupervised learning task. Our results extend the domain of application of
      modern stochastic network architectures to networks where synaptic transmission
      failure is the principal noise mechanism.

PMID- 29652582
TI  - Robust MST-Based Clustering Algorithm.
AB  - Minimax similarity stresses the connectedness of points via mediating elements
      rather than favoring high mutual similarity. The grouping principle yields
      superior clustering results when mining arbitrarily-shaped clusters in data.
      However, it is not robust against noises and outliers in the data. There are two
      main problems with the grouping principle: first, a single object that is far
      away from all other objects defines a separate cluster, and second, two connected
      clusters would be regarded as two parts of one cluster. In order to solve such
      problems, we propose robust minimum spanning tree (MST)-based clustering
      algorithm in this letter. First, we separate the connected objects by applying a
      density-based coarsening phase, resulting in a low-rank matrix in which the
      element denotes the supernode by combining a set of nodes. Then a greedy method
      is presented to partition those supernodes through working on the low-rank
      matrix. Instead of removing the longest edges from MST, our algorithm groups the
      data set based on the minimax similarity. Finally, the assignment of all data
      points can be achieved through their corresponding supernodes. Experimental
      results on many synthetic and real-world data sets show that our algorithm
      consistently outperforms compared clustering algorithms.

PMID- 29652583
TI  - New Families of Skewed Higher-Order Kernel Estimators to Solve the BSS/ICA
      Problem for Multimodal Sources Mixtures.
AB  - This letter suggests two new types of asymmetrical higher-order kernels (HOK)
      that are generated using the orthogonal polynomials Laguerre (positive or right
      skew) and Bessel (negative or left skew). These skewed HOK are implemented in the
      blind source separation/independent component analysis (BSS/ICA) algorithm. The
      tests for these proposed HOK are accomplished using three scenarios to simulate a
      real environment using actual sound sources, an environment of mixtures of
      multimodal fast-changing probability density function (pdf) sources that
      represent a challenge to the symmetrical HOK, and an environment of an adverse
      case (near gaussian). The separation is performed by minimizing the mutual
      information (MI) among the mixed sources. The performance of the skewed kernels
      is compared to the performance of the standard kernels such as Epanechnikov,
      bisquare, trisquare, and gaussian and the performance of the symmetrical HOK
      generated using the polynomials Chebyshev1, Chebyshev2, Gegenbauer, Jacobi, and
      Legendre to the tenth order. The gaussian HOK are generated using the Hermite
      polynomial and the Wand and Schucany procedure. The comparison among the 96
      kernels is based on the average intersymbol interference ratio (AISIR) and the
      time needed to complete the separation. In terms of AISIR, the skewed kernels'
      performance is better than that of the standard kernels and rivals most of the
      symmetrical kernels' performance. The importance of these new skewed HOK is
      manifested in the environment of the multimodal pdf mixtures. In such an
      environment, the skewed HOK come in first place compared with the symmetrical
      HOK. These new families can substitute for symmetrical HOKs in such applications.

PMID- 29652584
TI  - Optimal Readout of Correlated Neural Activity in a Decision-Making Circuit.
AB  - The neural correlates of decision making have been extensively studied with tasks
      involving a choice between two alternatives that is guided by visual cues. While
      a large body of work argues for a role of the lateral intraparietal (LIP) region
      of cortex in these tasks, this role may be confounded by the interaction between
      LIP and other regions, including medial temporal (MT) cortex. Here, we describe a
      simplified linear model of decision making that is adapted to two tasks: a motion
      discrimination and a categorization task. We show that the distinct contribution
      of MT and LIP may indeed be confounded in these tasks. In particular, we argue
      that the motion discrimination task relies on a straightforward visuomotor
      mapping, which leads to redundant information between MT and LIP. The
      categorization task requires a more complex mapping between visual information
      and decision behavior, and therefore does not lead to redundancy between MT and
      LIP. Going further, the model predicts that noise correlations within LIP should
      be greater in the categorization compared to the motion discrimination task due
      to the presence of shared inputs from MT. The impact of these correlations on
      task performance is examined by analytically deriving error estimates of an
      optimal linear readout for shared and unique inputs. Taken together, results
      clarify the contribution of MT and LIP to decision making and help characterize
      the role of noise correlations in these regions.

PMID- 29652585
TI  - A Theory of Sequence Indexing and Working Memory in Recurrent Neural Networks.
AB  - To accommodate structured approaches of neural computation, we propose a class of
      recurrent neural networks for indexing and storing sequences of symbols or analog
      data vectors. These networks with randomized input weights and orthogonal
      recurrent weights implement coding principles previously described in vector
      symbolic architectures (VSA) and leverage properties of reservoir computing. In
      general, the storage in reservoir computing is lossy, and crosstalk noise limits
      the retrieval accuracy and information capacity. A novel theory to optimize
      memory performance in such networks is presented and compared with simulation
      experiments. The theory describes linear readout of analog data and readout with
      winner-take-all error correction of symbolic data as proposed in VSA models. We
      find that diverse VSA models from the literature have universal performance
      properties, which are superior to what previous analyses predicted. Further, we
      propose novel VSA models with the statistically optimal Wiener filter in the
      readout that exhibit much higher information capacity, in particular for storing
      analog data. The theory we present also applies to memory buffers, networks with
      gradual forgetting, which can operate on infinite data streams without memory
      overflow. Interestingly, we find that different forgetting mechanisms, such as
      attenuating recurrent weights or neural nonlinearities, produce very similar
      behavior if the forgetting time constants are matched. Such models exhibit
      extensive capacity when their forgetting time constant is optimized for given
      noise conditions and network size. These results enable the design of new types
      of VSA models for the online processing of data streams.

PMID- 29652586
TI  - A Computational Account of the Role of Cochlear Nucleus and Inferior Colliculus
      in Stabilizing Auditory Nerve Firing for Auditory Category Learning.
AB  - It is well known that auditory nerve (AN) fibers overcome bandwidth limitations
      through the volley principle, a form of multiplexing. What is less well known is
      that the volley principle introduces a degree of unpredictability into AN neural
      firing patterns that may be affecting even simple stimulus categorization
      learning. We use a physiologically grounded, unsupervised spiking neural network
      model of the auditory brain with spike time dependent plasticity learning to
      demonstrate that plastic auditory cortex is unable to learn even simple auditory
      object categories when exposed to the raw AN firing input without subcortical
      preprocessing. We then demonstrate the importance of nonplastic subcortical
      preprocessing within the cochlear nucleus and the inferior colliculus for
      stabilizing and denoising AN responses. Such preprocessing enables the plastic
      auditory cortex to learn efficient robust representations of the auditory object
      categories. The biological realism of our model makes it suitable for generating
      neurophysiologically testable hypotheses.

PMID- 29652587
TI  - SuperSpike: Supervised Learning in Multilayer Spiking Neural Networks.
AB  - A vast majority of computation in the brain is performed by spiking neural
      networks. Despite the ubiquity of such spiking, we currently lack an
      understanding of how biological spiking neural circuits learn and compute in
      vivo, as well as how we can instantiate such capabilities in artificial spiking
      circuits in silico. Here we revisit the problem of supervised learning in
      temporally coding multilayer spiking neural networks. First, by using a surrogate
      gradient approach, we derive SuperSpike, a nonlinear voltage-based three-factor
      learning rule capable of training multilayer networks of deterministic integrate
      and-fire neurons to perform nonlinear computations on spatiotemporal spike
      patterns. Second, inspired by recent results on feedback alignment, we compare
      the performance of our learning rule under different credit assignment strategies
      for propagating output errors to hidden units. Specifically, we test uniform,
      symmetric, and random feedback, finding that simpler tasks can be solved with any
      type of feedback, while more complex tasks require symmetric feedback. In
      summary, our results open the door to obtaining a better scientific understanding
      of learning and computation in spiking neural networks by advancing our ability
      to train them to solve nonlinear problems involving transformations between
      different spatiotemporal spike time patterns.

PMID- 29652588
TI  - Joint Estimation of Effective Brain Wave Activation Modes Using EEG/MEG Sensor
      Arrays and Multimodal MRI Volumes.
AB  - In this letter, we present a new method for integration of sensor-based
      multifrequency bands of electroencephalography and magnetoencephalography data
      sets into a voxel-based structural-temporal magnetic resonance imaging analysis
      by utilizing the general joint estimation using entropy regularization (JESTER)
      framework. This allows enhancement of the spatial-temporal localization of brain
      function and the ability to relate it to morphological features and structural
      connectivity. This method has broad implications for both basic neuroscience
      research and clinical neuroscience focused on identifying disease-relevant
      biomarkers by enhancing the spatial-temporal resolution of the estimates derived
      from current neuroimaging modalities, thereby providing a better picture of the
      normal human brain in basic neuroimaging experiments and variations associated
      with disease states.

PMID- 29652589
TI  - Distributed Newton Methods for Deep Neural Networks.
AB  - Deep learning involves a difficult nonconvex optimization problem with a large
      number of weights between any two adjacent layers of a deep structure. To handle
      large data sets or complicated networks, distributed training is needed, but the
      calculation of function, gradient, and Hessian is expensive. In particular, the
      communication and the synchronization cost may become a bottleneck. In this
      letter, we focus on situations where the model is distributedly stored and
      propose a novel distributed Newton method for training deep neural networks. By
      variable and feature-wise data partitions and some careful designs, we are able
      to explicitly use the Jacobian matrix for matrix-vector products in the Newton
      method. Some techniques are incorporated to reduce the running time as well as
      memory consumption. First, to reduce the communication cost, we propose a
      diagonalization method such that an approximate Newton direction can be obtained
      without communication between machines. Second, we consider subsampled Gauss
      Newton matrices for reducing the running time as well as the communication cost.
      Third, to reduce the synchronization cost, we terminate the process of finding an
      approximate Newton direction even though some nodes have not finished their
      tasks. Details of some implementation issues in distributed environments are
      thoroughly investigated. Experiments demonstrate that the proposed method is
      effective for the distributed training of deep neural networks. Compared with
      stochastic gradient methods, it is more robust and may give better test accuracy.

PMID- 29652590
TI  - Why Does Large Batch Training Result in Poor Generalization? A Comprehensive
      Explanation and a Better Strategy from the Viewpoint of Stochastic Optimization.
AB  - We present a comprehensive framework of search methods, such as simulated
      annealing and batch training, for solving nonconvex optimization problems. These
      methods search a wider range by gradually decreasing the randomness added to the
      standard gradient descent method. The formulation that we define on the basis of
      this framework can be directly applied to neural network training. This produces
      an effective approach that gradually increases batch size during training. We
      also explain why large batch training degrades generalization performance, which
      previous studies have not clarified.

PMID- 29652591
TI  - A Reinforcement Learning Neural Network for Robotic Manipulator Control.
AB  - We propose a neural network model for reinforcement learning to control a robotic
      manipulator with unknown parameters and dead zones. The model is composed of
      three networks. The state of the robotic manipulator is predicted by the state
      network of the model, the action policy is learned by the action network, and the
      performance index of the action policy is estimated by a critic network. The
      three networks work together to optimize the performance index based on the
      reinforcement learning control scheme. The convergence of the learning methods is
      analyzed. Application of the proposed model on a simulated two-link robotic
      manipulator demonstrates the effectiveness and the stability of the model.

PMID- 29652592
TI  - Development of the Emergency Department Senior Abuse Identification (ED Senior
      AID) tool.
AB  - Emergency departments (EDs) are an important health care setting for the
      identification of elder abuse (EA). Our objective was to develop an ED-based tool
      to identify EA. The initial tool included a brief cognitive assessment, questions
      to detect multiple domains of EA, and a physical examination. Refinement of the
      tool was based on input from clinical experts and nurse and patient feedback. The
      revised tool, which included 15 questions about EA, was then tested in an
      academic ED. We calculated the inter-rater reliability, sensitivity, and
      specificity of individual EA questions. Among ED patients age>=65 (N = 259), 17
      (7%) screened positive for suspicion of EA. We identified a combination of six
      questions that cover the included domains of EA, demonstrated good or excellent
      inter-rater reliability, and had a sensitivity and specificity of 94% (95%
      confidence interval (CI) 71-100%) and 90% (95% CI 85-93%), respectively. These
      results inform a proposed screening tool for multisite validation testing.

PMID- 29652593
TI  - Vitamin D Status in Hospitalized Chronically Ill Patients.
AB  - OBJECTIVES: Vitamin D deficiency is rarely considered or treated in critically
      ill patients. Deficiency of 25-hydroxy vitamin D [25(OH)D] prior to hospital
      admission might be a significant predictor of short- and long-term all cause
      patient mortality in a critically ill patient. The aim of this work is to
      investigate the prevalence of vitamin D deficiency in hospitalized patients and
      its relation to the length of stay and outcome of hospitalization. METHODS:
      Prospective cohort study performed on 80 patients admitted with acute
      deterioration of their chronic illness. Four groups of diseases were included,
      namely, chronic liver diseases (CLD), chronic obstructive pulmonary diseases
      (COPD), cerebrovascular stroke (CVS), and heart failure (HF). The patients were
      followed up until their discharge, or transfer, or death. Patients were sampled
      for their vitamin D level on admission and were divided according to their
      vitamin D status into sufficient, insufficient, and deficient. Statistical
      methods and analysis of the present study were conducted using the SPSS V17
      program. RESULTS: Vitamin D level had a significant inverse correlation with
      length of hospital stay (r = -0.648) (p < 0.001). In vitamin D-deficient and 
      insufficient groups, there was a significant difference between survivors and
      nonsurvivors as regards vitamin D levels and an inverse correlation between
      vitamin D level and outcome of hospital admission. CONCLUSIONS: Vitamin D
      deficiency and insufficiency are significantly associated with a longer hospital
      stay and a poor outcome of hospital admission in comparison to control.

PMID- 29652594
TI  - Tissue Engineering and Regenerative Medicine 2017: A Year in Review.
AB  - In 2017, a new paradigm change caused by artificial intelligence and big data
      analysis resulted in innovation in each field of science and technology, and also
      significantly influenced progress in tissue engineering and regenerative medicine
      (TERM). TERM has continued to make technological advances based on
      interdisciplinary approaches and has contributed to the overall field of
      biomedical technology, including cancer biology, personalized medicine,
      development biology, and cell-based therapeutics. While researchers are aware
      that there is still a long way to go until TERM reaches the ultimate goal of
      patient treatment through clinical translation, the rapid progress in convergence
      studies led by technological improvements in TERM has been encouraging. In this
      review, we highlighted the significant advances made in TERM in 2017 (with an
      overlap of 5 months in 2016). We identified major progress in TERM in a manner
      similar to previous reviews published in the last few years. In addition, we
      carefully considered all four previous reviews during the selection process and
      chose main themes that minimize the duplication of the topics. Therefore, we have
      identified three areas that have been the focus of most journal publications in
      the TERM community in 2017: (i) advanced biomaterials and three-dimensional (3D)
      cell printing, (ii) exosomes as bioactive agents for regenerative medicine, and
      (iii) 3D culture in regenerative medicine.

PMID- 29652595
TI  - Stem Cells for Skeletal Muscle Tissue Engineering.
AB  - Volumetric muscle loss (VML) is a debilitating condition wherein muscle loss
      overwhelms the body's normal physiological repair mechanism. VML is particularly
      common among military service members who have sustained war injuries. Because of
      the high social and medical cost associated with VML and suboptimal current
      surgical treatments, there is great interest in developing better VML therapies.
      Skeletal muscle tissue engineering (SMTE) is a promising alternative to
      traditional VML surgical treatments that use autogenic tissue grafts, and rather
      uses isolated stem cells with myogenic potential to generate de novo skeletal
      muscle tissues to treat VML. Satellite cells are the native precursors to
      skeletal muscle tissue, and are thus the most commonly studied starting source
      for SMTE. However, satellite cells are difficult to isolate and purify, and it is
      presently unknown whether they would be a practical source in clinical SMTE
      applications. Alternative myogenic stem cells, including adipose-derived stem
      cells, bone marrow-derived mesenchymal stem cells, perivascular stem cells,
      umbilical cord mesenchymal stem cells, induced pluripotent stem cells, and
      embryonic stem cells, each have myogenic potential and have been identified as
      possible starting sources for SMTE, although they have yet to be studied in
      detail for this purpose. These alternative stem cell varieties offer unique
      advantages and disadvantages that are worth exploring further to advance the SMTE
      field toward highly functional, safe, and practical VML treatments. The following
      review summarizes the current state of satellite cell-based SMTE, details the
      properties and practical advantages of alternative myogenic stem cells, and
      offers guidance to tissue engineers on how alternative myogenic stem cells can be
      incorporated into SMTE research.

PMID- 29652596
TI  - Effect of Concurrent Visual Feedback Frequency on Postural Control Learning in
      Adolescents.
AB  - The purpose was to find better augmented visual feedback frequency (100% or 67%)
      for learning a balance task in adolescents. Thirty subjects were divided randomly
      into a control group, and 100% and 67% feedback groups. The three groups
      performed pretest (3 trials), practice (12 trials), posttest (3 trials) and
      retention (3 trials, 24 hours later). The reduced feedback group showed lower RMS
      in the posttest than in the pretest (p = 0.04). The control and reduced feedback
      groups showed significant lower median frequency in the posttest than in the
      pretest (p < 0.05). Both feedback groups showed lower values in retention than in
      the pretest (p < 0.05). Even when the effect of feedback frequency could not be
      detected in motor learning, 67% of the feedback was recommended for motor
      adaptation.

PMID- 29652597
TI  - Hypothyroidism During Tyrosine Kinase Inhibitor Therapy Is Associated with Longer
      Survival in Patients with Advanced Nonthyroidal Cancers.
AB  - BACKGROUND: Tyrosine kinase inhibitor (TKI)-induced thyroid dysfunction is
      recognized as a common adverse effect of treatment, but the importance of
      incident hypothyroidism during TKI therapy remains unclear. This study analyzed
      the prognostic significance of hypothyroidism during TKI therapy in cancer
      patients. METHODS: This was a retrospective cohort study of adult patients with
      advanced nonthyroidal cancer treated with TKI and available thyroid function
      testing at three affiliated academic hospitals from 2000 to 2017. Patients with
      preexisting thyroid disease were excluded. Demographic, clinical, and cancer
      treatment data were collected. Thyroid status with TKI treatment was determined
      from thyroid function testing and initiation of thyroid medication, and
      classified as euthyroid (thyrotropin [TSH] normal), subclinical hypothyroidism
      (SCH; TSH 5-10 mIU/L, or higher TSH if free thyroxine normal), or overt
      hypothyroidism (OH; TSH >10 mIU/L, low free thyroxine, or requiring replacement).
      Multivariate models were used to evaluate the effect of TKI-related
      hypothyroidism on overall survival (OS). RESULTS: Of 1120 initial patients, 538
      remained after exclusion criteria. SCH occurred in 72 (13%) and OH in 144 (27%)
      patients with TKI therapy. Patients with hypothyroidism had significantly longer
      OS, with median OS in euthyroid patients of 685 days [confidence interval (CI)
      523-851] compared to 1005 days [CI 634-1528] in SCH and 1643 days [CI 1215-1991]
      in OH patients (p < 0.0001). After adjustment for age, sex, race/ethnicity,
      cancer type, cancer stage, ECOG performance status, and checkpoint inhibitor
      therapy, OH remained significantly associated with OS (hazard ratio = 0.561; p <
      0.0001), whereas SCH did not (hazard ratio = 0.796; p = 0.165). Analysis of
      hypothyroid patients (SCH and OH) with TSH >5 and <10 mIU/L stratified by hormone
      replacement status showed improved survival associated with hormone replacement.
      CONCLUSIONS: New hypothyroidism in cancer patients treated with TKI is associated
      with significantly improved OS, should not necessitate TKI dose reduction or
      discontinuation, and may provide independent prognostic information.

PMID- 29652599
TI  - Risk Factors for New Hypothyroidism During Tyrosine Kinase Inhibitor Therapy in
      Advanced Nonthyroidal Cancer Patients.
AB  - BACKGROUND: Thyroid dysfunction during tyrosine kinase inhibitor (TKI) cancer
      treatment is common, but predisposing risk factors have not been determined.
      Recommendations for monitoring patients treated with one or multiple TKI and in
      conjunction with other relevant cancer therapies could be improved. The study
      objective was to assess the risk factors for new thyroid dysfunction in TKI
      treated previously euthyroid cancer patients. METHODS: A retrospective cohort
      study of patients with advanced nonthyroidal cancer treated with TKI from 2000 to
      2017, having available thyroid function tests showing initial euthyroid status,
      excluding patients with preexisting thyroid disease or lack of follow-up thyroid
      function tests. During TKI treatment, patients were classified as euthyroid
      (thyrotropin [TSH] normal), subclinical hypothyroidism (TSH 5-10 mIU/L, or higher
      TSH if free thyroxine normal), or overt hypothyroidism (TSH >10 mIU/L, low free
      thyroxine, or requiring thyroid hormone replacement). The timing of thyroid
      dysfunction and TKI used were assessed. Risk factors for incident hypothyroidism
      were evaluated using multivariate models. RESULTS: In 538 adult patients
      included, subclinical hypothyroidism occurred in 71 (13.2%) and overt
      hypothyroidism occurred in 144 (26.8%) patients with TKI therapy, following a
      median cumulative TKI exposure of 196 days (interquartile range [IQR] 63.5-518.5
      days). The odds of hypothyroidism were greatest during the first six months on a
      TKI. Median exposure time on the TKI concurrent with thyroid dysfunction in
      patients treated with only one TKI was 85 days (IQR 38-293.5 days) and was
      similar to the 74 days (IQR 38-133.3 days) in patients treated previously with
      other TKI (p = 0.41). Patients who developed hypothyroidism compared to those who
      remained euthyroid had greater odds of being female (odds ratio = 1.99
      [confidence interval 1.35-2.93], p < 0.01), but greater cumulative TKI exposure
      and greater number of TKI received were not associated with thyroid dysfunction.
      CONCLUSIONS: Thyroid dysfunction occurred in 40% of euthyroid patients.
      Monitoring thyroid function in TKI-treated patients is recommended, with
      particular attention to female patients and within the first six months of
      exposure to a new TKI.

PMID- 29652600
TI  - Social network analysis for assessing college-aged adults' health: A systematic
      review.
AB  - OBJECTIVE: Social network analysis (SNA) is a useful, emerging method for
      studying health. College students are especially prone to social influence when
      it comes to health. This review aimed to identify network variables related to
      college student health and determine how SNA was used in the literature.
      PARTICIPANTS: A systematic review of relevant literature was conducted in October
      2015. METHODS: Studies employing egocentric or whole network analysis to study
      college student health were included. We used Garrard's Matrix Method to extract
      data from reviewed articles (n = 15). RESULTS: Drinking, smoking, aggression,
      homesickness, and stress were predicted by network variables in the reviewed
      literature. Methodological inconsistencies concerning boundary specification,
      data collection, nomination limits, and statistical analyses were revealed across
      studies. CONCLUSIONS: Results show the consistent relationship between network
      variables and college health outcomes, justifying further use of SNA to research
      college health. Suggestions and considerations for future use of SNA are
      provided.

PMID- 29652601
TI  - Editorial.

PMID- 29652602
TI  - Barriers to resistance training among college-aged women.
AB  - OBJECTIVE: To examine resistance training (RT) barriers among college-aged women.
      PARTICIPANTS: Female college students (n = 223) from a Midwestern university.
      METHODS: Data were collected in September 2014. Participants completed a survey
      assessing demographics, current and past RT habits, and barriers to resistance
      training. Descriptive statistics were used to examine barrier agreement.
      Differences between current and past RT participation, residency, and class
      standing were analyzed. RESULTS: A majority of participants were Caucasian
      (78.9%) and, on average, 19.7 +/- 1.5 years of age; 52% participated in RT and
      46.6% met RT recommendations. Women who did not report current RT participation
      reported significantly higher mean agreement with all barriers, compared to those
      who do RT. Highest agreement was observed within socially based barriers.
      CONCLUSION: A majority of college-aged women are not meeting RT recommendations.
      Providing educational programs and avenues for finding same-sex RT partners may
      be most beneficial for overcoming common RT barriers.

PMID- 29652603
TI  - Draining the swamp while making America great again: senior dissonance in the age
      of Trump.
AB  - In his surprise election as president, Donald Trump enjoyed disproportionate
      electoral support from older voters, many of whom saw in Trump a person who would
      work to reverse demographic, economic, and cultural forces that had transformed
      American life as they had long seen it. Yet, Trump's campaign and incumbency has
      also been very much about gutting the Washington policy establishment of
      officials, bureaucrats, and lobbyists (aka, "the swamp") which, for more than
      half a century, has been instrumental in enacting and expanding legislation that
      has benefitted older Americans far more than any other social policy constituency
      in the country. This article contrasts the value-oriented electoral support Trump
      enjoyed from older Americans with their interest concerns centered on policies
      such as the Affordable Care Act, Medicaid, and a host of smaller grant-in-aid
      programs. It then reviews the strong institutional base seniors and their
      advocates have in Washington, posing whether interest-oriented concerns may
      outweigh ideological ones as policy options emerge from a Republican-controlled
      government prior to the 2018 elections.

PMID- 29652604
TI  - An Engineered Human Adipose/Collagen Model for In Vitro Breast Cancer Cell
      Migration Studies.
AB  - Adipocytes are one of the major stromal cell components of the human breast.
      These cells play a key role in the development of the gland and are implicated in
      breast tumorigenesis. Frequently, directional stromal collagen I fibers are found
      surrounding aggressive breast tumors. These fibers enhance breast cancer cell
      migration and are associated with poor patient prognosis. We sought to
      recapitulate these stromal components in vitro to provide a three-dimensional
      (3D) model comprising human adipose tissue and anisotropic collagen fibers. We
      developed a human mesenchymal stem cell (hMSC) cell line capable of undergoing
      differentiation into mature adipocytes by immortalizing hMSCs, isolated from
      breast reduction mammoplasties, through retroviral transduction. These
      immortalized hMSCs were seeded in engineered collagen I scaffolds with
      directional internal architecture, and adipogenesis was chemically induced,
      resulting in human adipose tissue being synthesized in vitro in an architectural
      structure associated with breast tumorigenesis. Subsequently, fluorescently
      labeled cells from an established breast cancer cell line were seeded into this
      model, cocultured for 7 days and imaged using multiphoton microscopy. Enhanced
      breast cancer cell migration was observed in the adipose-containing model over
      empty scaffold controls, demonstrating an adipocyte-mediated influence on breast
      cancer cell migration. Thus, this 3D in vitro model recapitulates the migratory
      effects of adipocytes observed on breast cancer cells and suggests that it could
      have utility with fresh breast tumor biopsies as an assay for cancer therapeutic
      efficacy in personalized medicine strategies.

PMID- 29652605
TI  - Improvement of Bone Healing by Neutralization of microRNA-335-5p, but not by
      Neutralization of microRNA-92A in Bone Marrow Mononuclear Cells Transplanted into
      a Large Femur Defect of the Rat.
AB  - Transplanted bone marrow mononuclear cells (BMC) support the healing of large
      bone defects. Neutralization of microRNA (MiR) that negatively affects key
      processes of the reparative response in BMC might help to further improve the
      beneficial effect of transplanted BMC in bone healing. Hence, the aim of this
      study was to evaluate if the neutralization of MiR-92A (vascularization) and MiR
      335-5p (osteogenic differentiation) in BMC using specific antiMiRs leads to a
      further improvement of the BMC-supported therapy of large bone defects. BMC
      transiently transfected with antiMiR- 92A, antiMiR-335, antiMiR-92A, and antiMiR
      355 or control antiMiR were seeded on beta-TCP (beta-tricalcium phosphate) and
      placed in a femoral large bone defect (5 mm) in Sprague-Dawley rats. Ultimate
      load as well as osseous integration of the beta-TCP-scaffolds were significantly
      improved in the antiMiR-335 group compared to the control group after 8 weeks,
      whereas neutralization of antiMiR-92A lead to an improvement of early
      vascularization after 1 week, but not to enhanced bone healing after 8 weeks. We
      demonstrated that the targeted inhibition of MiRs in transplanted BMC is a new
      approach that enhances BMC-supported bone healing.

PMID- 29652606
TI  - Development of PEI-RANK siRNA Complex Loaded PLGA Nanocapsules for the Treatment
      of Osteoporosis.
AB  - Osteoporosis, which is characterized by low bone mineral density and
      susceptibility to fracture, is caused by increased osteoclastic activity.
      Receptor activator of nuclear factor kappa B ligand (RANKL)/RANK signaling plays
      an important role in osteoclast differentiation and activation. The current
      treatment strategies for osteoporosis do not directly address this underlying
      cause and generates undesired side effects. This led to emergence of controlled
      delivery systems to increase drug bioavailability and efficacy specifically at
      the bone tissue. With better understanding of molecular pathology of bone, the
      use of small interfering RNA (siRNA) to inhibit translation of abnormal gene
      expression in cells is becoming a promising approach. In this study, we report a
      siRNA delivery system consisting of PEI:RANK siRNA complex entrapped in nanosized
      poly(lactic acid-co-glycolic acid) (PLGA) capsules intended to be used in the
      treatment of osteoporosis. The nanosize will enable the nanoparticles to be
      administered by intravenous injection. The RANK siRNA was complexed with
      polyethylenimine (PEI) and loaded into biodegradable PLGA nanocapsules (NCs). The
      PEI:RANK siRNA loaded nanocapsules significantly reduced (47%) RANK mRNA levels.
      The differentiation of osteoclast precursors to mature osteoclasts was
      significantly suppressed (~54%). The reduction in the osteoclastic activity of
      the differentiated osteoclasts (55%) was found to be statistically significant.
      The siRNA delivery system developed in the study is planned to be tested i.v. in
      mouse and has the potential to be used as a novel alternative approach for the
      systemic treatment of osteoporosis.

PMID- 29652607
TI  - Encapsulation of Mesenchymal Stem Cells Improves Vascularization of Alginate
      Based Scaffolds.
AB  - Vascularization of bioartificial tissues can be significantly enhanced by the
      generation of an arteriovenous (AV) loop. Besides the surgical vascularization,
      the choice of the scaffold and the applied cells are indispensable cofactors. The
      combination of alginate dialdehyde and gelatin (ADA-GEL) and mesenchymal stem
      cells (MSCs) is a promising approach with regard to biocompatibility,
      biodegradation, as well as de novo tissue formation. In this study, we targeted
      the investigation of the vascularization of ADA-GEL with and in the absence of
      encapsulated MSCs in the AV loop model. A Teflon chamber filled with ADA-GEL
      microcapsules was placed in the groin of Lewis rats and an AV loop was placed
      into the chamber. Group A encompassed the ADA-GEL without MSCs, whereas group B
      contained 2 * 106 DiI-labeled MSCs/mL ADA-GEL. Four weeks postoperatively, tissue
      formation and vascularization were investigated by histology and microcomputed
      tomography. We were able to prove vascularization originating from the AV loop in
      both groups with statistically significant more vessels in group B containing
      MSCs. Moreover, encapsulated MSCs promoted biodegradation of the ADA-GEL
      microcapsules. In the present study, we were able to demonstrate for the first
      time, the successful vascularization of ADA-GEL microcapsules by means of the AV
      loop. Furthermore, ADA-GEL displayed a good biocompatibility and encapsulation of
      MSCs into ADA-GEL microcapsule-enhanced vascularization as well as
      biodegradation.

PMID- 29652608
TI  - Immunomodulatory Role of Stem Cells from Human Exfoliated Deciduous Teeth on
      Periodontal Regeneration.
AB  - Periodontitis is initiated by the infection of periodontal bacteria and
      subsequent tissue inflammation due to immunoreaction, eventually leading to
      periodontal apparatus loss. Stem cells from human exfoliated deciduous teeth
      (SHEDs) have exhibited beneficial characteristics in dental tissue regeneration.
      However, the immunomodulatory functions of SHEDs have not been elucidated in the
      context of periodontitis treatment. In this study, we investigated the potential
      immunomodulatory effects of SHEDs on experimental periodontitis and demonstrated
      that multidose delivery of SHEDs led to periodontal tissue regeneration. SHEDs
      and monocytes/macrophages were cocultured in transwell systems and SHEDs were
      found to be capable of promoting monocyte/macrophage conversion to CD206+ M2-like
      phenotype. Bioluminescence imaging (BLI) was employed to assess the survival and
      distribution of SHEDs after delivery in periodontal tissues in an induced
      periodontitis model, and BLI revealed that SHEDs survived for ~7 days in
      periodontal tissues with little tissue diffusion. Then, multidose SHED delivery
      was applied to treat periodontitis at 7-day intervals. Results showed that
      mutidose SHEDs altered the cytokine expression profile in gingival crevicular
      fluid, reduced gum bleeding, increased new attachment of periodontal ligament,
      and decreased osteoclast differentiation. Micro-computed tomography analysis
      showed SHED administration significantly increased periodontal regeneration and
      alveolar bone volume, and decreased distance of cementoenamel junction to
      alveolar bone crest. Furthermore, an increase in the number of CD206+ M2
      macrophages was observed in periodontal tissues following the delivery of SHEDs,
      which aligned well with the promoted conversion to CD206+ M2-like cells from
      monocytes/macrophages in vitro after stimulation by SHEDs. This study
      demonstrated in a rat periodontitis model that local delivery of SHEDs attributed
      to the induction of M2 macrophage polarization, reduction of periodontal tissue
      inflammation, and enhancement of periodontal regeneration.

PMID- 29652609
TI  - An Optimized Collagen-Fibrin Blend Engineered Neural Tissue Promotes Peripheral
      Nerve Repair.
AB  - Tissue engineering approaches in nerve regeneration often aim to improve results
      by bridging nerve defects with conduits that mimic key features of the nerve
      autograft. One such approach uses Schwann cell self-alignment and stabilization
      within collagen gels to generate engineered neural tissue (EngNT). In this study,
      we investigated whether a novel blend of fibrin and collagen could be used to
      form EngNT, as before EngNT design a beneficial effect of fibrin on Schwann cell
      proliferation was observed. A range of blend formulations was tested in terms of
      mechanical behavior (gel formation, stabilization, swelling, tensile strength,
      and stiffness), and lead formulations were assessed in vitro. A 90% collagen 10%
      fibrin blend was found to promote SCL4.1/F7 Schwann cell viability and supported
      the formation of aligned EngNT, which enhanced neurite outgrowth in vitro (NG108
      cells) compared to formulations with higher and lower fibrin content. Initial in
      vivo tests in an 8 mm rat sciatic nerve model using rolled collagen-fibrin EngNT
      rods revealed a significantly enhanced axonal count in the midsection of the
      repair, as well as in the distal part of the nerve after 4 weeks. This optimized
      collagen-fibrin blend therefore provides a novel way to improve the capacity of
      EngNT to promote regeneration following peripheral nerve injury.

PMID- 29652610
TI  - Combination Therapy Comprising a Static Magnetic Field with Contractility
      Improves Skin Wounds.
AB  - Cutaneous wounds can present significant clinical problems because of abnormal
      healing after deep dermal damage. Despite technical advances in wound care, there
      are still unmet needs that result from inefficient treatment. In this study, we
      aimed to improve skin wound healing using a contractibility band with static
      magnetic field (SMF), termed a magnetic band (Mb). To examine the effect of the
      Mb on wound healing, full-thickness 15 * 35 mm excision wounds were surgically
      created on the dorsum of rats. An elastic and contractile band (nontreatment), or
      one neodymium magnet (Nd-1) or two magnets with an elastic and contractile band
      (Nd-2) were topically applied to the wound daily and the wound size was measured
      from day 1 to 7 after surgery. Nd-2 showed a significant (95%) reduction in the
      wound size on day 3. Histological analysis showed that proinflammatory cytokine
      levels were diminished by Nd-2, and granulation tissue and microvessels were
      increased compared with those in the sham group. During Mb-induced wound healing,
      apoptosis was significantly reduced and matrix remodeling-related factors were
      initially regulated. The results suggest that combination therapy comprising an
      SMF and an elastic and contractile band could be a promising tool to heal
      cutaneous wounds rapidly.

PMID- 29652611
TI  - An assisted living interprofessional education and practice geriatric screening
      clinic (IPEP-GSC): a description and evaluation.
AB  - As the U.S. population ages and lives longer, we need to assure that future
      providers are prepared to work in highly functioning interprofessional teams to
      deliver person-centered care for older adults with complex chronic conditions.
      Assisted living facilities are ideal venues in which to train interprofessional
      health sciences students in providing such care. After monthly clinics involving
      interprofessional students (from the colleges of medicine, nursing, pharmacy,
      public health, and school of social work) providing team-based care to older
      adults, students' post-clinic evaluations indicated perceived improvements in
      knowledge, attitudes, and perceptions about aging and care of older adults. In
      addition, participating older adults reported improved self-worth and enjoyment.
      The curriculum, evaluation outcomes, and lessons learned are described to support
      program replication.

PMID- 29652612
TI  - Quiet ego, self-regulatory skills, and perceived stress in college students.
AB  - OBJECTIVE: Examine the unique contributions of self-control and grit subscales
      (perseverance, interest consistency) as potential mediators of the relationship
      between quiet ego characteristics and less perceived stress in college students.
      PARTICIPANTS: Data from 1117 college students were collected between October,
      2015 and May, 2016. METHODS: The sample was split randomly into exploratory and
      confirmatory samples. Multiple mediator models were tested with PROCESS module
      (SPSS v. 24) in both samples. RESULTS: Hypotheses were largely confirmed with
      self-control fully mediating the link between quiet ego and perceived stress in
      both samples. CONCLUSIONS: Although many self-regulatory constructs may argue for
      their positive impact on college student outcomes, interventions that strengthen
      self-control, and not grit, may be most promising to reduce perceived stress.
      Further, interventions to strengthen quiet ego characteristics may be beneficial
      for strengthening self-control in college students.

PMID- 29652613
TI  - Knowledge and Concern about STIs/HIV and Sociodemographic Variables Associated
      with Getting Tested for HIV Among the General Population in Spain.
AB  - HIV testing is important in terms of prevention and treatment. However, HIV
      testing rates in the Spanish general population remains low. Therefore, HIV
      testing promotion constitutes a key issue. A high level of knowledge about
      HIV/AIDS is associated with having been tested for HIV. The general aim of this
      study was to determine the prevalence of people who had ever been tested for HIV
      in Spain. The sample consisted of 1,106 participants from the general population 
      60.0% females and 40.0% males - aged between 17 and 55 years old. The assessment
      instruments were a questionnaire on sociodemographic data and HIV testing, a
      scale of knowledge about STIs and HIV/AIDS, and a scale of concern about
      STIs/HIV. Results showed that greater knowledge about STIs and HIV was associated
      with a greater likelihood of being tested for HIV (OR = .77; 95.0% CI = .73-.82;
      p < .05). In addition, higher concern about HIV/AIDS decreased the likelihood of
      not having been tested for HIV (OR = .87; 95.0% CI = .83-.92; p < .05). In fact,
      the higher participants concern about STIs was, the lower their likelihood of not
      having been tested for HIV was (OR = .87; 95.0% CI = .83-.91; p < .05). It is
      necessary to promote HIV testing in the general population as well as to consider
      their socio-demographic and psychological characteristics.

PMID- 29652614
TI  - A Web-based review of sexual and reproductive health services available at
      colleges and universities in Georgia.
AB  - OBJECTIVE: Although two-thirds of graduating high school seniors attend college
      or university in the U.S., there is a paucity of national or state specific
      research regarding SRH services available on or near college and university
      campuses. METHODS: A review of websites for all colleges and universities in
      Georgia was conducted to evaluate sexual health services available on campuses
      and evidence of referral to community providers. RESULTS: Of 96 colleges in
      Georgia, 44 had campus-located health centers, with only 3 at two-year colleges.
      Overall SRH service provision was low, with great variation between colleges.
      Distances between colleges and Title X clinics ranged from 0.33 to 35.45 miles.
      CONCLUSIONS: Many students lack access to campus health centers, and information
      on college websites regarding SRH service availability and referrals differs
      dramatically between campuses. In the absence of robust campus-located services,
      schools should highlight where students can obtain comprehensive SRH care in the
      community.

PMID- 29652615
TI  - A longitudinal analysis of the relationships among daytime dysfunction, fatigue,
      and depression in college students.
AB  - OBJECTIVE: To examine the longitudinal trajectory of daytime dysfunction (DD) and
      its relationship with fatigue by depression status in university students.
      PARTICIPANTS: 243 students completed online surveys from September- December
      2016. METHODS: Surveys were conducted at three time points over a semester
      period: the beginning of the semester, the end of mid-term and the end of the
      semester. RESULTS: Results indicated that the DD significantly increased in all
      students over the semester. Students with depression showed a higher initial
      level of DD and faster rate of change compared to those without depression. A
      faster rate of change of DD predicted a higher level of end-semester fatigue.
      CONCLUSIONS: Depression is related to a higher initial level of DD and its faster
      rate change which in turn, predicted end-semester fatigue, identifying one of the
      possible pathways through which depression impacts the functioning and health of
      affected students.

PMID- 29652616
TI  - Ethical Predispositions to Violate or Obey Traffic Rules and the Mediating Role
      of Driving Styles.
AB  - Traffic law violations are the most important determinants of traffic accidents.
      This study examined the influence of drivers' ethical perspective on their
      traffic violations and the mediating role of driving styles in these
      relationships. A sample of 313 drivers participated in the study. Contrary to
      expectations, high ethical relativism was found to be associated with fewer
      aggressive traffic violations. This suggests that the informal normative system
      that parallels the official traffic regulations is the more salient reference
      against which drivers usually assess the adequacy of their behaviors, highly
      relativistic drivers being more willing to also take into consideration the
      official traffic code in these appraisals. We also found significant interactions
      between idealism and relativism on both ordinary and aggressive violations.
      Idealism emerged as a predictor of these violations only in drivers low in
      relativism. In this group, one's concern about the harm that he/she might cause
      to other traffic participants induces higher traffic law abidingness. These
      influences of idealism were mediated by certain driving styles. Drivers' general
      ethical perspective fosters a specific pattern of driving styles and,
      consequently, the tendency to commit or to refrain from traffic violations.

PMID- 29652617
TI  - Heart checks in college-age students link poor sleep to cardiovascular risk.
AB  - OBJECTIVE: To describe the relationships between the cardiovascular health,
      lifestyle behaviors, and lifestyle beliefs among college-age students.
      PARTICIPANTS: 729 college-aged students participated between October 2016 and
      April 2017. METHODS: Heart Checks, consisting of a cross-sectional survey and
      biometric screening, were conducted on a large Midwestern university campus.
      RESULTS: A small proportion of students (24.5%) engaged in the recommended 150+
      minutes of physical activity per week and 7.9% consumed 5+ servings of
      fruit/vegetables daily. Half (49.6%) slept 7 hours or less per night. Biometric
      screenings found that 26.4% of the students had high stress, 31.9% were
      overweight or obese, and 17.3% had pre-hypertension or hypertension. Less sleep
      was significantly associated with higher risks of being stressed, being
      overweight/obese, and having elevated blood pressure. CONCLUSIONS: Early
      detection, treatment, and education is critical to identify individuals at risk
      for cardiovascular disease and to promote healthy lifestyle changes before heart
      disease develops or progresses.

PMID- 29652618
TI  - Transcriptome Network Analysis Reveals Aging-Related Mitochondrial and
      Proteasomal Dysfunction and Immune Activation in Human Thyroid.
AB  - BACKGROUND: Elucidating aging-related transcriptomic changes in human organs is
      necessary to understand the aging physiology and mechanisms, but little is known
      regarding the thyroid gland. We investigated aging-related transcriptomic
      alterations in the human thyroid gland and characterized the related molecular
      functions. METHODS: Publicly available RNA sequencing data of 322 thyroid tissue
      samples from the Genotype-Tissue Expression project were analyzed. In addition,
      our own 64 RNA sequencing data of normal thyroid tissue samples were used as a
      validation set. To comprehensively evaluate the associations between aging and
      transcriptomic changes, we performed a weighted gene coexpression network
      analysis and pathway enrichment analysis. The thyroid differentiation score was
      then used for further analysis, defining the correlations between thyroid
      differentiation and aging. RESULTS: The most significant aging-related
      transcriptomic change in thyroid was the downregulation of genes related to the
      mitochondrial and proteasomal functions (p = 3 * 10-6). Moreover, genes that are
      associated with immune processes were significantly upregulated with age (p = 3 *
      10-4), and all of them overlapped with the upregulated genes in the thyroid
      glands affected by lymphocytic thyroiditis. Furthermore, these aging-related
      changes were not significantly different according to sex, but in terms of the
      thyroid differentiation, females were more susceptible to aging-related changes
      (p for trend = 0.03). CONCLUSIONS: Aging-related transcriptomic changes in the
      thyroid gland were associated with mitochondrial and proteasomal dysfunction,
      loss of differentiation, and activation of autoimmune processes. Our results
      provide clues to better understanding the age-related decline in thyroid function
      and higher susceptibility to autoimmune thyroid disease.

PMID- 29652619
TI  - Circulating Cytokine/Chemokine Concentrations Respond to Ionizing Radiation Doses
      but not Radiation Dose Rates: Granulocyte-Colony Stimulating Factor and
      Interleukin-18.
AB  - Exposure to ionizing radiation is a crucial life-threatening factor in nuclear
      and radiological incidents. It is known that ionizing radiation affects
      cytokine/chemokine concentrations in the blood of B6D2F1 mice. It is not clear
      whether radiation dose rates would vary the physiological response. Therefore, in
      this study we utilized data from two experiments using B6D2F1 female mice exposed
      to six different dose rates ranging from low to high rates. In one experiment,
      mice received a total dose of 8 Gy (LD0/30) of 60Co gamma radiation at four dose
      rates: 0.04, 0.15, 0.30 and 0.47 Gy/min. Blood samples from mice were collected
      at 24 and 48 h postirradiation for cytokine/chemokine measurements, including
      interleukin (IL)-1beta, IL-6, IL-10, keratinocyte cytokine (KC), IL-12p70, IL-15,
      IL-17A, IL-18, granulocyte-colony stimulating factor (G-CSF), granulocyte
      macrophage (GM)-CSF, macrophage (M)-CSF, monokine induced by gamma interferon
      (MIG), tumor necrosis factor (TNF)-alpha, fibroblast growth factor (FGF)-basic,
      vascular endothelial growth factor (VEGF) and platelet-derived growth factor
      basic (PDGF-bb). At 24 h after ionizing irradiation at dose rate of 0.04 Gy/min,
      significant increases were observed only in G-CSF and M-CSF ( P < 0.05). At 0.15
      Gy/min, IL-10, IL-17A, G-CSF and GM-CSF concentrations were increased. At 0.3
      Gy/min, IL-15, IL-18, G-CSF, GM-CSF, M-CSF, MCP-1, MIP-2, MIG, FGF-basic, VEGF
      and PDGF-bb were significantly elevated ( P < 0.05). At 0.47 Gy/min, IL-6, KC, IL
      10, MCP-1, G-CSF, GM-CSF and M-CSF were significantly increased. At 48 h
      postirradiation, all cytokines/chemokines except MCP-1 returned to or were below
      their baselines, suggesting these increases are transient at LD0/30 irradiation.
      Of note, there is a limitation on day 2 because cytokines/chemokines are either
      at or below their baselines. Other parameters such as fms-like tyrosine kinase
      receptor-3 ligand (Flt-3 ligand) concentrations and lymphocyte counts, which have
      proven to be unaffected by radiation dose rates, can be used instead for
      assessing the radiation dose. However, in a separate radiation dose and time
      course experiment, increases in IL-18 and G-CSF depended on the radiation doses
      but showed no significant differences between 0.58 and 1.94 Gy/min ( P > 0.05) at
      3 and 6 Gy but not 12 Gy. G-CSF continued to increase up to day 7, whereas IL-18
      increased on day 4 and remained above baseline level on day 7. Therefore, time
      after irradiation at different doses should be taken into consideration. To our
      knowledge, these results are the first to suggest that ionizing radiation, even
      at a very low-dose-rate (0.04 Gy/min), induces circulating G-CSF increases but
      not others for selected time points; radiation-induced increases in IL-18 at
      radiation dose rates between 0.15 and 1.94 Gy/min are also not in a radiation
      dose-rate-dependent manner. C-CSF, lymphocyte counts and circulating Flt-3 ligand
      should be explored further as possible biomarkers of radiation exposure at early
      time points. IL-18 is also worthy of further study as a potential biomarker at
      later time points.

PMID- 29652620
TI  - NASA GeneLab Project: Bridging Space Radiation Omics with Ground Studies.
AB  - Accurate assessment of risks of long-term space missions is critical for human
      space exploration. It is essential to have a detailed understanding of the
      biological effects on humans living and working in deep space. Ionizing radiation
      from galactic cosmic rays (GCR) is a major health risk factor for astronauts on
      extended missions outside the protective effects of the Earth's magnetic field.
      Currently, there are gaps in our knowledge of the health risks associated with
      chronic low-dose, low-dose-rate ionizing radiation, specifically ions associated
      with high (H) atomic number (Z) and energy (E). The NASA GeneLab project (
      https://genelab.nasa.gov/ ) aims to provide a detailed library of omics datasets
      associated with biological samples exposed to HZE. The GeneLab Data System (GLDS)
      includes datasets from both spaceflight and ground-based studies, a majority of
      which involve exposure to ionizing radiation. In addition to detailed information
      on radiation exposure for ground-based studies, GeneLab is adding detailed,
      curated dosimetry information for spaceflight experiments. GeneLab is the first
      comprehensive omics database for space-related research from which an
      investigator can generate hypotheses to direct future experiments, utilizing both
      ground and space biological radiation data. The GLDS is continually expanding as
      omics-related data are generated by the space life sciences community. Here we
      provide a brief summary of the space radiation-related data available at GeneLab.

PMID- 29652623
TI  - Beliefs underlying stress reduction and depression help-seeking among college
      students: An elicitation study.
AB  - OBJECTIVE: This study illustrates how a theory-based approach can identify
      college students' beliefs about stress reduction activities and help-seeking for
      depression. These beliefs are the basis for intervention design. PARTICIPANTS: A
      sample of 53 undergraduate students at a public university in the Midwest
      participated in this research during March 2016. METHODS: An open-ended belief
      elicitation survey was administered online. Beliefs were identified through
      qualitative thematic analyses. RESULTS: Exercise was students' most preferred
      stress reduction activity. Beliefs about exercise emphasized physical benefits
      yet also not having time for exercise. Beliefs about help-seeking for depression
      emphasized treatment efficacy, support from others, stigma, and time constraints.
      CONCLUSIONS: Whereas beliefs about positive outcomes inform educational and
      motivational messages, beliefs about time constraints underscore the need to also
      consider structural factors that can help students find time to attend to their
      well-being.

PMID- 29652622
TI  - Identity Crisis - Rigor and Reproducibility in Human Cell Lines.

PMID- 29652621
TI  - Dose-Modifying Factor of Radiation Therapy with Concurrent Cisplatin Treatment in
      HPV-Positive Squamous Cell Carcinoma: A Preclinical Study.
AB  - Human papillomavirus (HPV) is an important etiological factor in oropharyngeal
      squamous cell carcinoma (SCC). Compared to HPV-negative tumors, HPV-positive
      oropharyngeal SCC has shown a better response to nonsurgical treatments. In this
      study, we determined the dose-modifying factors for HPV-positive tumors with
      single-dose irradiation, with or without low radiosensitizing doses of cisplatin.
      In vitro, we determined an increased radiosensitivity of HPV-positive SCC, which
      might be a consequence of HPV-induced changes in the cell cycle regulation and
      DNA damage response, leading to increased cell death. Additionally, compared to
      HPV-negative tumors, 30% higher radiosensitivity of HPV-positive tumors was
      determined by tumor growth delay monitoring in immunodeficient mice in vivo.
      Concurrent cisplatin treatment had an additive effect in both HPV-negative and
      HPV-positive tumors, resulting in 20% better response in HPV-positive tumors than
      in HPV-negative tumors.

PMID- 29652624
TI  - Emergency Telemedicine: Achieving and Maintaining Compliance with the Emergency
      Medical Treatment and Labor Act.
AB  - PURPOSE: Telemedicine is a growing and important platform for medical delivery in
      the emergency department. Emergency telemedicine outlays often confront and
      conflict with important federal healthcare regulations. Because of this, academic
      medical centers, critical access hospitals, and other providers interested in
      implementing emergency telemedicine have often delayed or forgone such services
      due to reasonable fears of falling out of compliance with regulatory restrictions
      imposed by the Emergency Medical Treatment and Labor Act ("EMTALA"). This article
      offers insights into methods for implementing emergency telemedicine services
      while maintaining EMTALA compliance. METHODOLOGY: Critical analysis of EMTALA and
      its attendant regulations. RESULTS: The primary means of ensuring EMTALA
      compliance while implementing emergency telemedicine programs include
      incorporating critical clinical details into the services contracts and
      implementing robust written policies that anticipate division of labor issues,
      the need for backup coverage, triaging, patient transfer protocols, and
      credentialing issues. With adequate up-front due diligence and meaningful
      contracting, hospitals and telemedicine providers can avoid common EMTALA
      liability pitfalls.

PMID- 29652625
TI  - The Opportunity for Telehealth to Support Neurological Healthcare.
AB  - Neurological conditions affect one-third of Americans and are some of the most
      prevalent health issues in the country. Many sufferers have difficulty accessing
      treatment, however, advances in technology may be able to support availability,
      affordability, and convenience of care through telehealth services. This review
      outlines the current state of telemedicine in neurological healthcare,
      highlighting evidence-based research and use cases for digital services. Details
      on expenses associated with managing certain well-known conditions are included
      to shed light on the financial burden of disease and how telehealth can
      contribute to cost savings for patients and providers. Finally, a discussion of
      current telehealth legislature gives additional perspective on regulatory
      dynamics experienced by different stakeholders in the field. Research supports
      telemedicine as a solution to enhance current care models given its many
      benefits, including efficient and clinically useful service delivery. This
      movement has the opportunity to help billions of individuals globally by acting
      as a mechanism to provide impactful and scalable neurological healthcare.

PMID- 29652626
TI  - Endosteal and Perivascular Subniches in a 3D Bone Marrow Model for Multiple
      Myeloma.
AB  - The bone marrow microenvironment is the preferred location of multiple myeloma,
      supporting tumor growth and development. It is composed of a collection of
      interacting subniches, including the endosteal and perivascular niche. Current in
      vitro models mimic either of these subniches. By developing a model combining
      both niches, this study aims to further enhance the ability to culture primary
      myeloma cells in vitro. Also, the dependency of myeloma cells on each niche was
      studied. A 3D bone marrow model containing two subniches was created using 3D
      bioprinting technology. We used a bioprintable pasty calcium phosphate cement
      (CPC) scaffold with seeded osteogenic multipotent mesenchymal stromal cells (O
      MSCs) to model the endosteal niche, and Matrigel containing both endothelial
      progenitor cells (EPCs) and MSCs to model the perivascular niche. Within the
      model containing one or both of the niches, primary CD138+ myeloma cells were
      cultured and analyzed for both survival and proliferation. The 3D bone marrow
      model with combined subniches significantly increasing the proliferation of
      CD138+ myeloma cells compared to both environments separately. The developed
      model showed an essential role of the perivascular niche over the endosteal niche
      in supporting myeloma cells. The developed model can be used to study the
      expansion of primary myeloma cells and their interactions with varying bone
      marrow subniches.

PMID- 29652627
TI  - Visualizing Intrapopulation Hematopoietic Cell Heterogeneity with Self-Organizing
      Maps of SIMS Data.
AB  - Characterization of the heterogeneity within stem cell populations, which affects
      their differentiation potential, is necessary for the design of artificial
      cultures for stem cell expansion. In this study, we assessed whether self
      organizing maps (SOMs) of single-cell time-of-flight secondary ion mass
      spectrometry (TOF-SIMS) data provide insight into the spectral, and thus the
      related functional heterogeneity between and within three hematopoietic cell
      populations. SOMs were created of TOF-SIMS data from individual hematopoietic
      stem and progenitor cells (HSPCs), lineage-committed common lymphoid progenitors
      (CLPs), and fully differentiated B cells that had been isolated from murine bone
      marrow via conventional flow cytometry. The positions of these cells on the SOMs
      and the spectral variation between adjacent map units, shown on the corresponding
      unified distance matrix (U-matrix), indicated the CLPs exhibited the highest
      intrapopulation spectral variation, regardless of the age of the donor mice. SOMs
      of HSPCs, CLPs, and B cells isolated from young and old mice using the same
      surface antigen profiles revealed the HSPCs exhibited the most age-related
      spectral variation, whereas B cells exhibited the least. These results
      demonstrate that SOMs of single-cell spectra enable characterizing the
      heterogeneity between and within cell populations that lie along distinct
      differentiation pathways.

PMID- 29652628
TI  - Salience and Impact of Health Warning Label on Cigarette Packs in Vietnam:
      Findings From the Global Adult Tobacco Survey 2015.
AB  - Viet Nam is among the countries having highest rate of male smokers in the world.
      The country has joined the Global Tobacco Surveillance System since 2010. Under
      this system, two rounds of Global Adult Tobacco Survey (GATS) were conducted in
      2010 and 2015. Those two surveys provide excellent comparable data on tobacco
      usage and its related aspects in Vietnam. This study using the data from GATS
      2015 to examine the salience and impact of cigarette pack health warnings on
      quitting intention in Vietnam. The Vietnam GATS 2015 was a nationally
      representative survey in which 9,513 households were selected using two-stage
      random systematic sampling method. Results of multivariate analysis showed that
      the strongest predictor for quit intention because of health warnings was "ever
      made a quit attempt in the past 12 months" followed by "believes that tobacco
      smoking causes serious illness". Compared to GATS 2010, GATS 2015 observed the
      increase in salience of cigarette health warnings. However, the current pictorial
      health warnings are losing their impact on motivating intention to quit. The
      results highlight that it is time to start the rotation cycle to refresh the
      current health warning set. Actions to select a new and more impressive set of
      pictorial health warnings should be developed as soon as possible.

PMID- 29652629
TI  - Quantifying the magnitude and potential influence of missing data in campus
      sexual assault surveys: A systematic review of surveys, 2010-2016.
AB  - OBJECTIVE: To understand how missing data may influence conclusions drawn from
      campus sexual assault surveys. METHODS: We systematically reviewed 40 surveys
      from 2010-2016. We constructed a pseudo-population of the total population
      targeted across schools, creating records proportional to the respective response
      rate and reported sexual assault prevalence. We simulated the effects of 9
      scenarios where the sexual assault prevalence among nonresponders differed from
      that of responders. RESULTS: The surveys represented a total female undergraduate
      population of 317,387 with only 77,966 (24.6%) survey responses. Among
      responders, 20.4% reported experiences of sexual assault. However, prevalence of
      sexual assault could theoretically range from 5.0 to 80.4% under extreme
      assumptions about prevalence in nonresponders. Smaller, but still significant
      differences were observed with less extreme assumptions. CONCLUSIONS: Missing
      data are widespread in campus sexual assault surveys. Conclusions drawn from
      these incomplete data are highly sensitive to assumptions about the sexual
      assault prevalence among nonresponders.

PMID- 29652630
TI  - Effects of a sleep hygiene text message intervention on sleep in college
      students.
AB  - OBJECTIVE: To test the effectiveness of a text-message intervention to promote
      sleep hygiene to improve sleep in young adult college students. PARTICIPANTS: A
      convenience sample of undergraduate students from one Southwestern university (n
      = 96), 18-26 years old, recruited in August 2015. METHODS: A 2-group pretest
      posttest experimental design assigned participants to receive biweekly text
      messages about sleep hygiene or healthy behaviors for 6 weeks. Survey questions
      addressed sleep knowledge, sleep hygiene, self-efficacy for sleep hygiene, and
      sleep quality at baseline and posttest. RESULTS: Though not significant, sleep
      quality, sleep hygiene, and sleep knowledge improved in both groups. CONCLUSIONS:
      Self-efficacy for sleep hygiene is a modifiable factor that may serve to improve
      sleep quality. Sleep quality improved in both groups. Text messaging is a
      feasible approach to delivering an intervention to promote healthy behaviors
      among young adults.

PMID- 29652631
TI  - "This is not a drill": Activation of a student-led influenza vaccination point of
      dispensing.
AB  - OBJECTIVE: To describe activation of a Point of dispensing (POD) in response to
      an influenza outbreak, highlighting the use of a student-led model. PARTICIPANTS:
      Faculty, staff, and students of Harris College of Nursing and Health Sciences,
      Texas Christian University (TCU), as well as those located in its primary
      building. METHODS: In response to an August 2017 influenza outbreak, a
      vaccination clinic was conducted for a target population through POD activation.
      The larger campus community was served through provision of additional doses by
      the Texas Christian University Health Center and the annual October student-led
      vaccination clinic. RESULTS: Eleven additional cases were diagnosed after
      vaccinations began. CONCLUSIONS: One hundred percent of the targeted population
      was vaccinated (n = 824), with an additional 127 participants vaccinated (others
      working in the building where POD held also vaccinated). This was the first time
      POD activation had occurred on campus in response to an outbreak.

PMID- 29652632
TI  - Lessons for environmental health sciences from "Perceptions of science in
      America".

PMID- 29652633
TI  - Glucose, insulin, and the carotid body chemoreceptors in humans.
AB  - Known primarily for its oxygen-sensing capabilities, the carotid body
      chemoreceptors have recently been implicated, primarily by work in animal models,
      in the pathophysiology of a number of metabolic conditions. The research
      presented in this brief review highlights translational work conducted at the
      Mayo Clinic between 2010 and 2017 in healthy humans and discusses key areas for
      future work in disease populations.

PMID- 29652635
TI  - FAR2 is associated with kidney disease in mice and humans.
AB  - Mesangial matrix expansion is an important process in the initiation of chronic
      kidney disease, yet the genetic factors driving its development are unknown. Our
      previous studies have implicated Far2 as a candidate gene associated with
      differences in mesangial matrix expansion between mouse inbred strains.
      Consistent with the hypothesis that increased expression of Far2 leads to
      mesangial matrix expansion through increased production of platelet-activating
      factor precursors, we show that FAR2 is capable of mediating de novo platelet
      activating factor synthesis in vitro and driven by the transcription factor
      NKX3.2. We demonstrate that knockdown of Far2 in mice delays the progression of
      mesangial matrix expansion with at least six months (equivalent to ~15 yr in
      human). Furthermore, we show that increased FAR2 expression in human patients is
      associated with diabetic nephropathy, lupus nephritis, and IgA nephropathy. Taken
      together, these results highlight FAR2's role in the development of mesangial
      matrix expansion and chronic kidney disease.

PMID- 29652634
TI  - Emerging applications of genome-editing technology to examine functionality of
      GWAS-associated variants for complex traits.
AB  - Over the last decade, genome-wide association studies (GWAS) have propelled the
      discovery of thousands of loci associated with complex diseases. The focus is now
      turning toward the function of these association signals, determining the causal
      variant(s) among those in strong linkage disequilibrium, and identifying their
      underlying mechanisms, such as long-range gene regulation. Genome-editing
      techniques utilizing zinc-finger nucleases (ZFN), transcription activator-like
      effector nucleases (TALENs), and clustered regularly-interspaced short
      palindromic repeats with Cas9 nuclease (CRISPR-Cas9) are becoming the tools of
      choice to establish functionality for these variants, due to the ability to
      assess effects of single variants in vivo. This review will discuss examples of
      how these technologies have begun to aid functional analysis of GWAS loci for
      complex traits such as cardiovascular disease, Type 2 diabetes, cancer, obesity,
      and autoimmune disease. We focus on analysis of variants occurring within
      noncoding genomic regions, as these comprise the majority of GWAS variants,
      providing the greatest challenges to determining functionality, and compare
      editing strategies that provide different levels of evidence for variant
      functionality. The review describes molecular insights into some of these
      potentially causal variants and how these may relate to the pathology of the
      trait and look toward future directions for these technologies in post-GWAS
      analysis, such as base-editing.

PMID- 29652637
TI  - Asthma and allergy as risk factors for suicidal behavior among young adults.
AB  - : An association between allergic disease, depression and suicidality has been
      reported. OBJECTIVE: To explore the relationships between suicidality and asthma,
      allergy, internet addiction, stress, sleep quality, pain/discomfort, and
      depression, among emerging adults. PARTICIPANTS: 929 college students completed
      an online survey between October 2015 and April 2017. METHODS: A cross-sectional
      study using multivariate analysis techniques was implemented. RESULTS: Using
      structural equation modeling, we found that allergies and stress were directly
      related to pain/discomfort; pain/discomfort was associated to poor sleep,
      depression, and suicidality. Sleep quality was also affected by stress; while
      sleep, stress, pain/discomfort, and internet addiction were directly related to
      depression (all p < .05). Ultimately, four factors impacted suicidality: stress,
      pain/discomfort, depression, and, indirectly, sleep quality (all p < .05).
      Although allergy had some effects, these did not reach statistical significance
      (p < .09). CONCLUSION: Findings suggest that allergy might impact suicidality
      indirectly through increased pain/discomfort, poor sleep, and depression.

PMID- 29652636
TI  - HIF1 mediates a switch in pyruvate kinase isoforms after myocardial infarction.
AB  - Alternative splicing of RNA is an underexplored area of transcriptional response.
      We expect that early changes in alternatively spliced genes may be important for
      responses to cardiac injury. Hypoxia inducible factor 1 (HIF1) is a key
      transcription factor that rapidly responds to loss of oxygen through alteration
      of metabolism and angiogenesis. The goal of this study was to investigate the
      transcriptional response after myocardial infarction (MI) and to identify novel,
      hypoxia-driven changes, including alternative splicing. After ligation of the
      left anterior descending artery in mice, we observed an abrupt loss of cardiac
      contractility and upregulation of hypoxic signaling. We then performed RNA
      sequencing on ischemic heart tissue 1 and 3 days after infarct to assess early
      transcriptional changes and identified 89 transcripts with altered splicing. Of
      particular interest was the switch in Pkm isoform expression (pyruvate kinase,
      muscle). The usually predominant Pkm1 isoform was less abundant in ischemic
      hearts, while Pkm2 and associated splicing factors (hnRNPA1, hnRNPA2B1, Ptbp1)
      rapidly increased. Despite increased Pkm2 expression, total pyruvate kinase
      activity remained reduced in ischemic myocardial tissue. We also demonstrated
      HIF1 binding to PKM by chromatin immunoprecipitation, indicating a direct role
      for HIF1 in mediating this isoform switch. Our study provides a new, detailed
      characterization of the early transcriptome after MI. From this analysis, we
      identified an HIF1-mediated alternative splicing event in the PKM gene. Pkm1 and
      Pkm2 play distinct roles in glycolytic metabolism and the upregulation of Pkm2 is
      likely to have important consequences for ATP synthesis in infarcted cardiac
      muscle.

PMID- 29652638
TI  - Efficacy of interventions targeting alcohol, drug and smoking behaviors in
      university and college students: A review of randomized controlled trials.
AB  - OBJECTIVE: To evaluate the effectiveness of interventions targeting alcohol
      consumption, drug use and smoking for college/university students. PARTICIPANTS:
      College/University students. METHODS: Studies were eligible if: (1)included
      students attending universities/colleges; (2)implemented in a university/college
      setting; (3)aimed to improve at least one of the following behaviors: alcohol
      and/or drug use and/or smoking; (4)were RCTs. The effect of the interventions on
      behaviors was determined by the percentage of studies that reported an effect.
      Due to the heterogeneity of outcomes meta-analysis was not conducted. RESULTS: 88
      studies met criteria. University-based interventions were effective for reducing
      alcohol-related outcomes (drinking patterns, BAC, consequences, problem
      drinking). Inconsistent findings for drug and smoking were observed. CONCLUSIONS:
      University-based interventions have the potential to improve health for students.
      While there is a breadth of research examining the efficacy of interventions to
      reduce alcohol consumption, further research is needed to determine the best
      approach for addressing smoking and drug use among students.

PMID- 29652639
TI  - Does Family Cohesion Predict Children's Effort? The Mediating Roles of Sense of
      Coherence, Hope, and Loneliness.
AB  - The degree of cohesion and support within families has often been considered a
      predictor of students' effort-investment and success in school. The objectives of
      this study are to examine the roles of personal factors (i.e., sense of coherence
      and hopeful thinking) as well as interpersonal factors (i.e., loneliness) in
      mediating the relationship between family cohesion and effort. The sample
      consists of 1719 elementary school children (781 boys and 938 girls) from the
      fifth and six grades (mean age = 10.25, SD = 0.70) of 29 elementary schools in
      central Israel. Students answered study questionnaires in the middle of their
      academic year. Analyses utilizing hierarchical multiple regression and Hayes'
      bootstrapping approach (PROCESS; Preacher & Hayes, 2008) were used. The results
      support the distinctive contribution of family cohesion and the mediating roles
      of sense of coherence and hope (as protective factors) as well as loneliness (as
      a risk factor) in predicting students' school effort. This study has important
      educational implications, emphasizing the value of promoting hopeful thinking and
      coping with loneliness in helping students to thrive in their studies.

PMID- 29652640
TI  - Echinococcus multilocularis Surveillance Using Copro-DNA and Egg Examination of
      Shelter Dogs from an Endemic Area in Hokkaido, Japan.
AB  - Surveillance of Echinococcus multilocularis infection among 156 shelter dogs was
      conducted in an urban area (Sapporo city) in Hokkaido, where the parasite is
      endemic in Japan using copro-DNA and fecal egg examination from September 2013 to
      April 2017. Echinococcus infection was detected in three dogs (1.9%), including
      one dog that excreted eggs. The results suggested that free-roaming or stray dogs
      in urban area may be infected by capturing wild voles containing parasitic cysts
      and could be a source of human infection. Dog-to-human transmission is a
      significant concern, and the risk of such transmission is present even in urban
      areas in Hokkaido. We recommend deworming within 1 month (e.g., before egg
      excretion) of capture for free-roaming or stray dogs in Echinococcus-endemic area
      to prevent potential human infection.

PMID- 29652641
TI  - Molecular Detection of Bartonella Species in Blood-Feeding Bat Flies from Mexico.
AB  - Bartonellae are emerging blood-borne bacteria that have been recovered from a
      wide range of mammalian species and arthropod vectors around the world. Bats are
      now recognized as a potential wildlife reservoir for a diverse number of
      Bartonella species, including the zoonotic Candidatus B. mayotimonensis. These
      bat-borne Bartonella species have also been detected in the obligate
      ectoparasites of bats, such as blood-feeding flies, which could transmit these
      bacteria within bat populations. To better understand this potential for
      transmission, we investigated the relatedness between Bartonella detected or
      isolated from bat hosts sampled in Mexico and their ectoparasites. Bartonella
      spp. were identified in bat flies collected on two bat species, with the highest
      prevalence in Trichobius parasiticus and Strebla wiedemanni collected from common
      vampire bats (Desmodus rotundus). When comparing Bartonella sequences from a
      fragment of the citrate synthase gene (gltA), vector-associated strains were
      diverse and generally close to, but distinct from, those recovered from their
      bacteremic bat hosts in Mexico. Complete Bartonella sequence concordance was
      observed in only one bat-vector pair. The diversity of Bartonella strains in bat
      flies reflects the frequent host switch by bat flies, as they usually do not live
      permanently on their bat host. It may also suggest a possible endosymbiotic
      relationship with these vectors for some of the Bartonella species carried by bat
      flies, whereas others could have a mammalian host.

PMID- 29652642
TI  - Powassan Virus Disease in the United States, 2006-2016.
AB  - BACKGROUND: Powassan virus (POWV) is a tick-borne flavivirus that causes rare,
      but often severe, disease in humans. POWV neuroinvasive disease was added to the
      U.S. nationally notifiable disease list in 2001 and nonneuroinvasive disease was
      added in 2004. The only previous review of the epidemiology of POWV disease in
      the United States based on cases reported to the Centers for Disease Control and
      Prevention (CDC) covered the period from 1999 through 2005. METHODS: We describe
      the epidemiology and clinical features of laboratory-confirmed POWV disease cases
      reported to CDC from 2006 through 2016. RESULTS: There were 99 cases of POWV
      disease reported during the 11-year period, including 89 neuroinvasive and 10
      nonneuroinvasive disease cases. There was a median of seven cases per year
      (range: 1-22), with the highest numbers of cases reported in 2011 (n = 16), 2013
      (n = 15), and 2016 (n = 22). Cases occurred throughout the year, but peaked in
      May and June. Cases were reported primarily from northeastern and north-central
      states. Overall, 72 (73%) cases were in males and the median age was 62 years
      (range: 3 months-87 years). Of the 11 (11%) cases who died, all were aged >50
      years. The average annual incidence of neuroinvasive POWV disease was 0.0025
      cases per 100,000 persons. CONCLUSIONS: POWV disease can be a severe disease and
      has been diagnosed with increased frequency in recent years. However, this might
      reflect increased disease awareness, improved test availability, and enhanced
      surveillance efforts. Clinicians should consider POWV disease in patients
      presenting with acute encephalitis or aseptic meningitis who are resident in, or
      have traveled to, an appropriate geographic region.

PMID- 29652643
TI  - Expression of a Recombinant Nucleocapsid Protein of Rift Valley Fever Virus in
      Vero Cells as an Immunofluorescence Antigen and Its Use for Serosurveillance in
      Traditional Cattle Herds in Zambia.
AB  - The open reading frame of the nucleocapsid protein (NP) of Rift Valley fever
      virus (RVFV) strain MP12 was cloned and expressed in Vero E6 cells. The
      recombinant NP (rNP)-expressing cells were used as antigens for an indirect
      immunofluorescent antibody assay (IFA). The rNP-based IFA and RVFV-infected Vero
      E6 cell (authentic antigen)-based IFA showed similar IFA profiles with immune
      rabbit serum, which was prepared by immunization with rNP expressed using a
      baculovirus vector. A total of 942 traditional cattle sera obtained in five
      districts in Central, Southern, and Western provinces of Zambia were screened for
      anti-RVFV antibodies by the authentic antigen-based and rNP-based IFAs.
      Significant agreement was obtained between the two IFAs. The findings show that
      the rNP-based IFA is a safe and useful diagnostic tool as an alternative to the
      authentic antigen-based IFA. The antibody titers given by the rNP-based IFA were
      higher than those by the authentic antigen-based IFA. Therefore, the rNP-based
      IFA might be useful for serosurveillance of RVFV infection among cattle. Antibody
      prevalence rates in the five districts were 1.3% to 13.5% in the authentic
      antigen-based IFA and 6.0% to 21.4% in the rNP-based IFA. The results indicated
      that despite no reports of active cases of RVF in these provinces of Zambia, the
      virus is circulating among cattle herds.

PMID- 29652644
TI  - Alphaviruses: Serological Evidence of Human Infection in Paraguay (2012-2013).
AB  - INTRODUCTION: Alphaviruses can produce febrile illness and encephalitis in dead
      end hosts such as horses and humans. Within this genus, the Venezuelan Equine
      Encephalitis virus (VEEV) complex includes pathogenic epizootic subtypes and
      enzootic subtypes that are not pathogenic in horses (except subtype IE, Mexican
      strains), although they can cause febrile symptoms in humans. The Rio Negro virus
      (RNV-VEEV subtype VI) circulates in Argentina, where it was associated with
      undifferentiated febrile illness. Mayaro (MAYV) and Una (UNAV) viruses belong to
      a different group, the Semliki Forest virus complex, with confirmed circulation.
      OBJECTIVE: The present study aimed to determine RNV, MAYV, and UNAV
      seroprevalences by plaque reduction neutralization test in 652 samples of
      Paraguayan individuals mainly from the Central Department, between years 2012 and
      2013. METHODS: Samples with antibodies titer >1:20 against RNV were also tested
      for Mosso das Pedras-subtype IF, subtype IAB, and Pixuna (PIXV)-subtype IV
      viruses that belongs to VEEV antigenic complex. RESULTS: The overall
      seroprevalence of RNV was 3.83%, and for UNAV it was 0.46%, and no neutralizing
      antibodies were detected against MAYV in the studied population. Two of the
      twenty-seven heterotypic samples were positive for PIXV. The 50.1% of
      neutralizing antibody titers against RNV were high (equal to or greater than
      1/640), suggesting recent infections. The effect of age on the prevalence of RNV
      was negligible. CONCLUSIONS: These results bring new information about neglected
      alphaviruses in South America, and these data will serve as the basis for future
      studies of seroprevalence of other VEEV, and studies to search potential hosts
      and vectors of these viruses in the region.

PMID- 29652645
TI  - Application of a Nonpaper Based Matrix to Preserve Chikungunya Virus Infectivity
      at Ambient Temperature.
AB  - For over 100 years, field studies on arboviruses and the subsequent delivery and
      administration of live attenuated vaccines have been complicated by the need to
      maintain a so-called "cold chain," which is the source to destination
      refrigeration of biological materials. In this study we describe the application
      of a nonpaper based matrix and demonstrate preservation of chikungunya virus
      infectivity at ambient temperature for 7 days. The technique was successfully
      employed using infectious cell culture medium and infected mosquito homogenate
      samples. This technique provides a simple solution for conducting studies in
      resource-limited areas, where the maintenance of a cold chain is technically
      challenging.

PMID- 29652646
TI  - Molecular Survey of Head and Body Lice, Pediculus humanus, in France.
AB  - Human lice, Pediculus humanus, are obligate blood-sucking parasites.
      Phylogenetically, they belong to several mitochondrial clades exhibiting some
      geographic differences. Currently, the body louse is the only recognized disease
      vector, with the head louse being proposed as an additional vector. In this
      article, we study the genetic diversity of head and body lice collected from
      Bobigny, a town located close to Paris (France), and look for louse-borne
      pathogens. By amplifying and sequencing the cytb gene, we confirmed the presence
      of clades A and B in France. Besides, by amplifying and sequencing both cytb and
      cox1 gene, we reported, for the first time, the presence of clade E, which has
      thus far only been found in lice from West Africa. DNA from Bartonella quintana
      was detected in 16.7% of body lice from homeless individuals, but in none of the
      head lice collected from 47 families. Acinetobacter DNA was detected in 11.5% of
      head lice belonging to all three clades and 29.1% of body lice. Six species of
      Acinetobacter were identified, including two potential new ones. Acinetobacter
      baumannii was the most prevalent, followed by Candidatus Acinetobacter Bobigny-1,
      Acinetobacter calcoaceticus, Acinetobacter nosocomialis, Acinetobacter junii, and
      Candidatus Acinetobacter Bobigny-2. Body lice were found to be infected only with
      A. baumannii. These findings show for the first time, the presence of clade E
      head lice in France. This study is also the first to report the presence of DNAs
      of several species of Acinetobacter in human head lice in France.

PMID- 29652647
TI  - Prevalence and predictors of PTSD among a college sample.
AB  - OBJECTIVE: This study examined the prevalence and correlates of probable
      posttraumatic stress disorder (PTSD) in freshman entering college and prospective
      associations of probable PTSD with additional outcomes. PARTICIPANTS: 2,310
      students with data collected from Fall 2014 through Spring 2015. METHODS:
      Incoming freshman completed a survey assessing for relevant variables at the
      beginning of fall semester and during the spring semester. RESULTS: Seventy
      percent of the sample endorsed experiencing at least one potentially traumatic
      event (PTE). 34.4% of PTE exposed individuals met criteria for probable PTSD.
      Female sex, higher depressive and anxiety symptoms, and interpersonal PTE count
      were positively associated with PTSD symptoms. Higher PTSD symptoms were
      associated with higher anxiety and depressive symptoms, and new-onset
      interpersonal PTE. CONCLUSIONS: Identification of factors contributing to risk
      for PTSD is essential to inform prevention and intervention efforts. Intervention
      efforts should be targeted to students experiencing PTSD symptoms as they enter
      college.

PMID- 29652648
TI  - Pre-S2 Start Codon Mutation of Hepatitis B Virus Subgenotype B3 Effects on NF
      kappaB Expression and Activation in Huh7 Cell Lines.
AB  - A cross-sectional study on hepatitis B patients in Indonesia showed association
      of pre-S2 start codon mutation (M120 V) with cirrhosis and hepatocellular
      carcinoma (HCC), which was dissimilar from studies from other populations where
      pre-S2 deletion mutation was more prevalent. Different mutation patterns were
      attributed to different hepatitis B virus (HBV) subgenotypes in each population
      study. HBV surface proteins are reported to induce the activation of NF-kappaB, a
      transcriptional factor known to play an important role in the development of
      liver disease. This study aimed to see the effects of HBs variants in HBV
      subgenotype B3 on the expression and activation of NF-kappaB as one of the
      mechanisms in inducing advanced liver disease. HBV subgenotypes B3, each carrying
      wild-type (wt) HBs, M120 V, and pre-S2 deletion mutation were isolated from three
      HCC patients. HBs genes were amplified and cloned into pcDNA3.1 and were
      transfected using Lipofectamine into a Huh7 cell line. NF-kappaB activation was
      measured through IkappaB-alpha expression, which is regulated by NF-kappaB. RNA
      expressions for HBs, IkappaB-alpha, and NF-kappaB subunit (p50) were evaluated
      using real-time PCR. M120 V mutant had a significantly higher mRNA level compared
      with wt and pre-S2 deletion mutant; however, there were no significant
      differences in HBs protein expressions. The transcription level of p50 was higher
      in M120 V mutation compared with HBs wild-type and pre-S2 deletion mutant. NF
      kappaB activation was higher in HBs wild-type compared with the two mutant
      variants. Pre-S2 mutations had no effect on the increment of NF-kappaB
      activation. However, M120 V mutation may utilize a different pathway in liver
      disease progression that involves high expression of NF-kappaB subunit, p50.

PMID- 29652649
TI  - Complications of HIV Infection.

PMID- 29652650
TI  - The alcohol contexts of consent, wanted sex, sexual pleasure, and sexual assault:
      Results from a probability survey of undergraduate students.
AB  - OBJECTIVE: To examine, in a probability sample of undergraduate students,
      characteristics of students' most recent sexual experiences (including alcohol
      use) as well as their experiences with nonconsensual sex. PARTICIPANTS: In
      January and February 2015, 22,046 students were invited to participate in an
      anonymous, cross-sectional, Internet-based survey; 7,032 surveys were completed
      (31.9%). METHODS: Measures included background characteristics (age, gender,
      sexual orientation), most recent sexual event items (sexual pleasure, wantedness,
      alcohol use), and experiences with nonconsensual sex (since college and
      lifetime). RESULTS: Respondents reporting sober consensual sex were more likely
      to report higher levels of sexual pleasure and wantedness. Nonconsensual oral,
      vaginal, or anal penetration occurring during college were reported by 15.8% of
      women and 7.7% of men. Students more often told friends, partners, or family
      members and rarely disclosed to university faculty or police. CONCLUSIONS:
      Implications for campus policy and health education are addressed.

PMID- 29652651
TI  - Prediction of organ involvement in systemic sclerosis by serum biomarkers and
      peripheral endothelial function.
AB  - OBJECTIVES: To identify prognostic factors among serum biomarkers and endothelial
      vasodilator function findings in patients with systemic sclerosis (SSc). METHODS:
      This is a clinical observational study. We assessed 60 consecutive SSc patients
      (44 limited cutaneous-type, 16 diffuse cutaneous-type). Circulating growth
      differentiation factor-15 (GDF-15), placenta growth factor (PlGF), endostatin,
      vascular endothelial growth factor (VEGF), and pentraxin 3 (PTX3) were measured
      by ELISA. Peripheral endothelial function was measured by forearm blood
      dilatation response to brachial artery occlusion using noninvasive
      plethysmography (EndoPAT2000), which is associated with nitric-oxide-dependent
      vasodilatation and yields a reactive hyperemia index (RHI). We evaluated whether
      abnormalities in these values were associated with type of SSc - namely, diffuse
      cutaneous SSc (dcSSc) or limited cutaneous SSc (lcSSc) - or organ involvement
      including interstitial lung disease (ILD), digital ulcer (DU) and estimated right
      ventricular systolic pressure (RVSP) by echocardiography >30 mmHg. RESULTS: SSc
      patients showed significantly elevated serum GDF-15, PlGF, endostatin and VEGF
      but not PTX3 compared with controls. GDF-15 and PlGF were high in dcSSc patients.
      EndoPAT-RHI was low, and incidence of RVSP >30 mmHg was high in dcSSc.
      Multivariate analysis revealed that elevated GDF-15 was highly predictive of
      dcSSc, ILD or RVSP >30 mmHg. PlGF for DU was also found. Conversely, a low
      EndoPAT-RHI value was predictive of the presence of dcSSc, ILD or DU.
      CONCLUSIONS: This is the first study to inclusively investigate the relationships
      among biomarkers, EndoPAT-RHI and organ involvement in patients with SSc. Our
      data suggest a complex pathological progression of SSc through fibrotic
      impairment and microvascular damage.

PMID- 29652652
TI  - Circulating follicular helper T cells (CD4+CXCR5+ICOS+) decrease in patients with
      rheumatoid arthritis treated with abatacept.

PMID- 29652653
TI  - Role of foetal umbilical artery Doppler on prediction of adverse pregnancy
      outcomes in patients with systemic lupus erythematosus.
AB  - OBJECTIVES: To investigate the foetal outcomes and examine the predictive value
      of the third-trimester umbilical artery Doppler in systemic lupus erythematosus
      (SLE) pregnancies. METHODS: Data of 180 pregnancies in 175 SLE patients from Jan
      2007 to Jan 2017 were analysed retrospectively. Pulsatility index (PI),
      resistance index (RI), and systolic/diastolic ratio (S/D) of the umbilical artery
      flow velocity data were monitored by Doppler ultrasound. RESULTS: One or more
      composite adverse pregnancy outcomes (APOs) occurred in 46.7% of patients with
      SLE. A total of 62 (34.4%) pregnancies were pre-term birth, and 34 (18.9%)
      newborns were small for gestational age (SGA). Twenty-two of pregnancies (12.2%)
      resulted in foetal distress. In multivariate analysis, predictors of composite
      APOs included positive anti-Ro (OR 5.5, 95% CI 1.7-18.2, p=0.005) and low
      complement (OR 3.9, 95% CI 1.1-13.6, p=0.04). Doppler PI, RI, and S/D were
      significantly higher in the pre-term birth, SGA, and composite APO groups than in
      the patients without APOs. RI with cut-off values of 0.57 and 0.70 indicated the
      highest risk of pre-term birth and composite APOs, with sensitivities of 50.0%
      and 21.4%, as well as specificities of 59.6% and 97.7%, respectively. PI emerged
      as the best predictor of SGA. The optimal cutoff value for PI was 0.77, at which
      sensitivity (90.9%) and specificity (49.2%) had the best combination.
      CONCLUSIONS: Pregnancies in lupus still had an increased risk of APOs in terms of
      pre-term birth. Third-trimester umbilical artery Doppler was useful in predicting
      pre-term birth, SGA, and composite APOs in lupus pregnancies.

PMID- 29652654
TI  - Patients with juvenile idiopathic arthritis become adults: the role of
      transitional care.
AB  - Most juvenile idiopathic arthritis (JIA) patients need to attend adult
      rheumatology centres to continue the clinical management of their disease and to
      receive adequate long-term treatment. Transition from the paediatric to the adult
      health care team is a critical moment in the clinical history of these patients,
      but unfortunately, about 50% of the transfer processes to adult rheumatology are
      not successful, putting these patients at high risk of unfavourable outcomes.
      There are several obstacles to the success of transitional care for JIA patients,
      such as the absence of specific criteria for the assessment of disease activity,
      the lack of specific treatment recommendations for JIA adult patients, the poor
      adolescent-specific training for adult rheumatologists, and the shortage of
      resources. The improvement in the transition process in medical care has become a
      priority in many health care systems, but not many studies evaluating transition
      models, and common methodologies for measuring transition outcomes are available.
      The aim of this review is to identify and describe the models of transitional
      care in JIA, providing insights and recommendations to develop effective
      transitional care models in this disease.

PMID- 29652655
TI  - Effect of tumour necrosis factor-alpha inhibitors on renal function in patients
      with rheumatoid arthritis from the KOBIO registry from 2012 to 2016.
AB  - OBJECTIVES: The effect of biological disease-modifying anti-rheumatic drugs
      (bDMARDs) on renal function in patients with rheumatoid arthritis (RA) has not
      been well established. We assessed whether tumour necrosis factor (TNF)
      inhibitors could affect renal function in RA. METHODS: A total of 2110 patients
      with RA enrolled in the Korean College of Rheumatology Biologics (KOBIO) registry
      were analysed. All patients were taking bDMARDs or conventional synthetic DMARDs
      (csDMARDs). Renal function was evaluated by calculating the estimated glomerular
      filter rate (eGFR) using the Modification of Diet in Renal Disease (MDRD)
      equation. Renal insufficiency was defined as eGFR <60 mL/min/1.73 m2. Differences
      in eGFR changes between different types of DMARDs were assessed at each follow-up
      time using the generalised linear model (GLM) method. Risk factors for renal
      insufficiency were identified using binary logistic regression analysis. RESULTS:
      The changes of eGFR values in patients treated with TNF inhibitors were not
      significantly different from those with csDMARDs alone or non-TNF inhibitors in
      all RA patients regardless of renal function. Among patients with renal
      insufficiency, GLM analysis revealed that the changes of eGFR values by TNF
      inhibitors were also compatible to those treated with csDMARDs alone or non-TNF
      inhibitors. Older age (>55 years), longer disease duration (>5 years), and use of
      methotrexate were identified as clinical determinants for renal insufficiency.
      CONCLUSIONS: TNF inhibitors did not influence the change of renal function during
      RA treatment. TNF inhibitors may be a safe treatment option irrespective of renal
      function.

PMID- 29652656
TI  - Electrocardiogram abnormalities related to anti-malarials in systemic lupus
      erythematosus.
AB  - OBJECTIVES: Cardiotoxicity with potential conduction/structural abnormalities on
      electrocardiogram (ECG) have been reported with anti-malarial (AM). We aimed to
      study whether cumulative AM is associated with ECG abnormalities. METHODS: A
      standard resting supine ECG was performed on consecutive patients attending the
      Lupus Clinic since 2012. ECG abnormalities were grouped into structural [left
      ventricular hypertrophy or atrial enlargement] and conduction abnormalities
      [prolonged corrected QT interval (QTc), short PR interval, left bundle branch
      block (LBBB), right bundle branch block (RBBB) and atrioventricular block (AVB),
      bradycardia, tachycardia, premature atrial complex, ectopic atrial rhythm, atrial
      fibrillation, premature ventricular complex and ventricular bigeminy].
      Associations between cumulative AM and ECG abnormalities (structural or
      conduction) were assessed using logistic regression analysis (after adjusting for
      baseline patient characteristics) and in a nested case-control study (1:3).
      RESULTS: Of 453 patients treated with AM, the median cumulative AM was 1207 grams
      at ECG. Conduction abnormalities were more prevalent than structural
      abnormalities, 71 (15.7%) vs. 58 (12.8%). AM cumulative dose did not show a
      statistical significant association with ECG structural abnormalities, (OR 1.82,
      p=0.07) while it was protective for conduction ECG abnormalities (OR 0.42,
      p=0.006). The nested case-control analysis also found that AM cumulative dose is
      protective against conduction ECG abnormalities (OR 0.36, p=0.0007). SLE duration
      was a risk factor for both structural and conduction ECG abnormalities.
      CONCLUSIONS: This study suggests an association between cumulative AM dose above
      the median (1207 g) and structural ECG abnormalities. More importantly,
      cumulative AM decreases the odds of ECG conduction abnormalities.

PMID- 29652657
TI  - Detection of anti-neutrophil cytoplasmic and antinuclear autoantibodies favouring
      misdiagnoses in 5 cases of Erdheim-Chester disease.

PMID- 29652658
TI  - Bcl-XL and Mcl-1 upregulation by calreticulin promotes apoptosis resistance of
      fibroblast-like synoviocytes via activation of PI3K/Akt and STAT3 pathways in
      rheumatoid arthritis.
AB  - OBJECTIVES: Fibroblast-like synoviocytes (FLS) play key roles in synovium
      hyperplasia and pannus formation in rheumatoid arthritis (RA). The present study
      was undertaken to explore the mechanisms that calreticulin (CRT) promoted anti
      apoptosis of RA FLS. METHODS: The expression of CRT and anti-apoptotic proteins
      Bcl-XL and Mcl-1 in RA synovium were detected by immunohistochemistry. The
      expression of Bcl-XL and Mcl-1 in RA FLS by CRT were determined. The
      phosphorylation of Akt and STAT3 was detected by western blot. The effect of CRT
      on proliferation of RA FLS was examined by MTT assay. The ability of CRT to
      inhibit RA FLS apoptosis was assessed by flow cytometry. RESULTS: Increased
      expressions of CRT, Bcl-XL and Mcl-1 were detected in RA synovium compared with
      osteoarthritis (OA). Moreover, CRT expression correlated positively with Bcl-XL
      and Mcl-1 in RA, respectively. In vitro, CRT induced upregulation of Bcl-XL and
      Mcl-1 protein levels in RA FLS, in dose/time dependent manners. Upregulated
      expression of Bcl-XL and Mcl-1 induced by CRT were inhibited by PI3K/Akt or STAT3
      pathways inhibitors in RA FLS, respectively. The increased phosphorylation levels
      of Akt and STAT3 were also detected with CRT incubation, in dose/time dependent
      manners. Additionally, CRT rescued apoptosis of RA FLS mediated by FasL.
      CONCLUSIONS: This study showed that upregulation of Bcl-XL and Mcl-1 expression
      in RA FLS by CRT were PI3K/Akt and STAT3 signal pathways dependent, and promoted
      the anti-apoptosis of RA FLS. Therefore, this may represent a therapeutic target
      for the treatment of RA.

PMID- 29652659
TI  - Efficiency of dose reduction strategy of etanercept in patients with axial
      spondyloarthritis.
AB  - OBJECTIVES: To evaluate the efficacy of different tapering or discontinuation
      strategies of etanercept in a cohort of axial spondyloarthritis from South China.
      METHODS: We performed a retrospective cohort study. Axial SpA patients who
      achieved clinical remission for at least 6 months after receiving a standard dose
      of etanercept therapy were enrolled. Different tapering or discontinuation
      strategies were compared. RESULTS: Altogether, 258 cases were enrolled. No
      differences were found in baseline characteristics among the three groups.
      Significantly more patients on discontinuation group (19%) than tapering group
      (5.4%, p<0.001) relapsed as early as 6 months. Almost all of the patients
      (103/107, 96.3%) in taper 25% group and more than 80% (71/88, 80.7%) of the
      patients in taper 50% group maintained low disease activity (LDA) or clinical
      remission during the first year. At the end of the 2-year follow-up, the
      percentage of patients maintaining LDA or remission were 28.6% (discontinuation),
      55.7% (taper 50%), 84.1% (taper 25%), respectively. Activity indexes were
      significantly lower in taper 25% group compared to the other two groups. Patients
      in discontinuation group and tapering 50% group, with longer SpA duration were
      more likely to relapse, and remission>12 months before discontinuation/tapering
      helped to reduce relapse. CONCLUSIONS: It is feasible to slowly increase the
      dosing interval and transit to the lowest effective dosing interval for some
      patients in remission/LDA. Prolonging the time under remission before tapering
      help to improve the outcome. Tapering 25% of the etanercept dose every 3 months
      may be a pragmatic approach for more cost-effective use of the drug.

PMID- 29652660
TI  - Cognitive function of patients with rheumatoid arthritis is associated with
      disease activity but not carotid atherosclerotic changes.
AB  - OBJECTIVES: Although the relationship between atherosclerosis and cognitive
      impairment has been studied and replicated, whether cognitive deficits in RA can
      be attributed to atherosclerotic changes is not well understood. This study
      investigated cognitive function in patients with RA and evaluated whether
      cognitive function was affected by carotid arterial atherosclerosis. METHODS: We
      examined 70 RA patients and 40 healthy controls. RA activity was assessed by
      disease activity score with 28 joint-erythrocyte sedimentation rate (DAS28-ESR).
      Cognitive function was assessed by the Korean version of the Consortium to
      Establish a Registry for Alzheimer's disease (CERAD-K) neuropsychological
      battery. Carotid arteries were scanned for the presence of plaques and to assess
      intima-media thickness (IMT). We assessed potential risk factors of cognitive
      impairment in RA patients using regression analyses. RESULTS: There was a
      significant difference between RA patients and healthy controls in the verbal
      fluency (p=0.004) and Boston naming test (p=0.035). Carotid ultrasound revealed
      significantly more plaque in RA patients than in healthy controls (p=0.017). RA
      patients with memory impairment had significantly higher DAS28-ESR scores
      (p<0.001), age (p=0.009), and mean cIMT (p=0.027) than RA patients without memory
      impairment. In multivariable regression analysis, CERAD-K total score showed a
      significant negative correlation with age (beta=-0.415, p<0.001) or DAS28-ESR
      (beta=-4.685, p<0.001), but no correlation was found between CERAD-K total score
      and presence of plaque or cIMT. CONCLUSIONS: Our results indicate that disease
      activity of RA and aging contribute to cognitive dysfunction, but there was no
      association between cognitive function and carotid atherosclerotic changes in RA
      patients.

PMID- 29652661
TI  - Combined brain and heart magnetic resonance imaging in systemic vasculitides:
      fiction or real need?
AB  - Systemic vasculitides (SVs) is a group of diseases characterised by
      inflammation/necrosis of the blood vessel wall in various organs. Simultaneous
      brain and heart involvement is a cause of increased morbidity/mortality in SV. We
      aimed to present evidence of concurrent brain/heart involvement in SV and the
      role of a combined brain/heart magnetic resonance imaging (MRI) in their risk
      stratification. Cerebral vasculitis (CV) can be presented as focal deficits,
      seizures, headache, neuropsychiatric manifestations or cognitive dysfunction and
      cardiovascular disease (CVD) as myocardial/vascular inflammation,
      perfusion/function defects and fibrosis. MRI is a non-invasive, non-radiating
      technique that allows the reliable identification of intraparenchymal brain
      lesions and the detection of myocardial/vascular inflammation and fibrosis.
      However, its use in SV is currently hampered by high cost, lack of
      availability/expertise and lack of awareness among the clinicians. Although there
      are no clinical data supporting the combined use of brain/heart MRI in
      asymptomatic SV, it would be called for in cases with clinical suspicion of
      brain/heart involvement, especially in those at high risk for CVD/stroke such as
      SLE/APS. Furthermore, it may be of value in SV with multi-organ involvement,
      cognitive dysfunction or other neuropsychiatric symptoms with concurrent cardiac
      involvement, presenting as typical or atypical symptoms with normal routine
      cardiac evaluation, new onset of arrhythmia and/or HF.

PMID- 29652662
TI  - Sialylated isoforms of apolipoprotein C-III and plasma lipids in subjects with
      coronary artery disease.
AB  - BACKGROUND: Apolipoprotein C-III (ApoC-III), a key regulator of plasma
      triglyceride (TG), is present in three isoforms, i.e. non-sialylated (ApoC-III0),
      monosialylated (ApoC-III1) and disialylated (ApoC-III2). We aimed at quantifying
      the distribution of the ApoC-III glycoforms in patients with angiographically
      demonstrated coronary artery disease (CAD) according to levels of total ApoC-III
      plasma concentration. METHODS: ApoC-III glycoforms were quantified by a
      specifically developed, high-resolution, mass spectrometry method in unrelated
      CAD patients. Lipoprotein lipase (LPL) activity was estimated by a fluorescence
      based method. RESULTS: In 101 statin-treated CAD patients, the absolute
      concentrations of the three glycoforms similarly increased across ApoC-III
      quartiles, but the proportion of ApoC-III1 rose whereas that of ApoC-III0
      decreased progressively by increasing total ApoC-III concentrations. The
      proportion of ApoC-III2 was quite constant throughout the whole range of total
      ApoC-III. A higher proportion of ApoC-III1 reflected an unfavorable lipid profile
      characterized by high levels of TG, total and low density lipoprotein
      cholesterol, ApoE and reduced ApoA-I. The correlations between ApoC-III
      glycoforms and TG were confirmed in 50 statin-free CAD patients. High
      concentration of total ApoC-III was associated with low LPL activity, while no
      correlation was found for the relative proportion of glycoforms. CONCLUSIONS:
      Specific patterns of ApoC-III glycoforms are present across different total ApoC
      III concentrations in CAD patients. The inhibitory effect of ApoC-III on LPL
      appears related to total ApoC-III concentration, but not to the relative
      proportion of ApoC-III glycoforms.

PMID- 29652663
TI  - Multiple myeloma and macro creatine kinase type 1: the first case report.

PMID- 29652664
TI  - Alcohol use in adolescence: 5 years admissions at a pediatric emergency
      department.
AB  - Objective To characterize the profile and pattern of alcohol consumption in
      adolescents, admitted with acute alcoholic intoxication (AAI) at a pediatric
      emergency department of North Portugal. Methods Retrospective descriptive study
      of adolescents aged between 10 and 17 years, admitted with AAI between 2012 and
      2016. The following variables were evaluated: age, gender, drinking context,
      quantity and type of alcohol, Glasgow Coma Scale (GCS), previous episodes,
      associated injuries, transport to the emergency department, other drug
      consumption, blood alcohol level (BAL), blood glucose level, treatment and
      orientation. The chi2/Fisher's exact test and t-Student test were performed (p <
      0.05). Results A total of 180 adolescents with AAI presented. The majority of
      adolescents were older than 15 years old (71%) and 3% were younger than 14 years
      old. The mean age was 15.9 years [standard deviation (SD) 1.1 years] and 65% were
      males. The most common type of alcohol consumed was distilled drinks (60%).
      Recurrent alcohol use was identified in 7% and binge drinking was reported in 37%
      of patients. The mean BAL was 1.58 g/L (SD 0.6 g/L) and there were other drug
      consumptions (mainly cannabinoids) observed in 11% of patients. After emergency
      department discharge, 17% were followed at hospital consultation. There was no
      significant difference between boys and girls or between BAL and injuries or
      other drugs consumption. Conclusion This study confirms a high rate of alcohol
      use among adolescents, in particular "heavy episodic drinking", revealing an easy
      access to alcohol at this age. The integration of alcohol use prevention programs
      in community and education systems should be encouraged and implemented in every
      adolescent consultation.

PMID- 29652665
TI  - Effect of flavonol and its dimethoxy derivatives on paclitaxel-induced peripheral
      neuropathy in mice.

PMID- 29652666
TI  - Effect of a multidisciplinary treatment program on eating behavior in overweight
      and obese preschool children.
AB  - BACKGROUND: The effects of multidisciplinary treatment programs on eating
      behavior in overweight preschool-aged children are largely unknown. We evaluated
      a multidisciplinary intervention program on eating behavior in 3- to 5-year-old
      overweight children, comparing them with children given standard treatment. We
      also assessed the parental eating behavior changes and investigated associations
      between parents and children. METHODS: We randomized 75 children to a
      multidisciplinary intervention or to a standard care program. During a 16-week
      period, children and parents in the multidisciplinary group were given dietary
      advice, physical activity sessions and, for parents only, psychological
      counseling. Children and parents in the standard group visited a pediatrician 3
      times and were given information on a healthy lifestyle. At baseline, after 16
      weeks, and after 12 months, children were measured and parents completed the
      Dutch Child Eating Behavior Questionnaire (DEBQ-C) for their children and the
      DEBQ for themselves. RESULTS: At the three time points, 70 (93.3%), 57 (91.9%),
      and 42 (73.7%) DEBQ-Cs were analyzed. We found no differences in the changes in
      eating behavior between the two groups over time. In both groups, there was a
      significant increase in restrained eating behavior present at 16 weeks, however,
      this was no longer present at 12 months. We found no associations between changes
      in eating behavior between the children and their parents. CONCLUSIONS: A
      multidisciplinary obesity intervention program in preschool-aged children induced
      more restrained eating behavior between baseline and 16 weeks. However, there was
      no difference with the children in the standard care group.

PMID- 29652667
TI  - Glycated hemoglobin A1c as a screening test for detecting type 2 diabetes
      mellitus in obese children and adolescents.
AB  - BACKGROUND: The diagnostic cutoff points for indicators of type 2 diabetes
      mellitus (T2DM) in the pediatric population have not been defined thus far.
      METHODS: A retrospective, single-center study was conducted from April 2003 to
      May 2016. We enrolled 236 overweight or obese children and adolescents aged 4-17
      years. Thirty-nine (26.9%) of 145 patients had T2DM according to the oral glucose
      tolerance test results. RESULTS: A glycated hemoglobin (HbA1c) level of 6.5% had
      a sensitivity and specificity of 87.2% and 98.5%, respectively, for detecting
      T2DM. The optimal HbA1c cutoff level for T2DM was >6.2% (94.7% sensitivity, 95.5%
      specificity). CONCLUSIONS: We observed that the use of an HbA1c level of 6.5% had
      a lower sensitivity for detecting T2DM than an HbA1c level of >6.2%.

PMID- 29652668
TI  - Still too little, too late? Ten years of growth hormone therapy baseline data
      from the NordiNet(r) International Outcome Study.
AB  - BACKGROUND: We investigated time trends in age, gender, growth hormone (GH) dose
      and height standard deviation score (SDS) in children with GH deficiency (GHD),
      born small for gestational age (SGA) or with Turner syndrome (TS) starting GH
      treatment. METHODS: Data were obtained from children enrolled in the NordiNet(r)
      International Outcome Study (IOS) between 2006 and 2015 in the Czech Republic,
      France, Germany, Serbia and Montenegro (all indications), and Switzerland and the
      UK (GHD only). Trends were analyzed by linear regression. Patients were divided
      by age into early-, medium- or late-start groups in three different time periods.
      RESULTS: Approximately one-third of children starting treatment for GHD were
      girls, with no apparent increase in proportion over time. The mean baseline age
      for starting treatment decreased significantly (p<0.001) for both GHD and SGA in
      the Czech Republic and Germany. In the other countries studied, over 40% of
      children started treatment for GHD and SGA late (girls >10, boys >11 years)
      between 2013 and 2015. The mean baseline GH doses were largely within recommended
      ranges for GHD and SGA, but below the lowest recommended starting dose for TS in
      almost every year since 2011 except in France. CONCLUSIONS: Approximately one
      third of children starting treatment for GHD were girls. Between 2013 and 2015,
      more than 40% of children started treatment for GHD and SGA late except in
      Germany and the Czech Republic. TS patients received below-recommended doses.
      These results highlight the need for earlier identification of short stature in
      children, particularly girls, and for dose optimization in TS.

PMID- 29652669
TI  - Endophytic Bacillus spp. from medicinal plants inhibit mycelial growth of
      Sclerotinia sclerotiorum and promote plant growth.
AB  - Plant growth-promoting bacteria that are also capable of suppressing plant
      pathogenic fungi play an important role in sustainable agriculture. There is a
      critical need for conducting research to discover, characterize and evaluate the
      efficacy of new strains of such bacteria in controlling highly aggressive plant
      pathogens. In this study, we isolated endophytic bacteria from medicinal plants
      of Bangladesh and evaluated their antagonistic capacity against an important
      phytopathogenic fungus Sclerotinia sclerotiorum. Growth-promoting effects of
      those isolates on cucumber and rice seedlings were also assessed. Among 16
      morphologically distinct isolates, BDR-2, BRtL-2 and BCL-1 significantly
      inhibited the growth of S. sclerotiorum through induction of characteristic
      morphological alterations in hyphae and reduction of mycelial dry weight. When
      cucumber and rice seeds were treated with these endophytic bacteria, seven
      isolates (BCL-1, BDL-1, BRtL-2, BRtL-3, BDR-1, BDR-2 and BBoS-1) enhanced seed
      germination, seedling vigor, seedling growth and number of roots per plant at a
      varying level compared to untreated controls. All isolates produced high levels
      of indole-3-acetic acid (6 to 63 MUg/mL) in vitro. Two most potential isolates,
      BDR-2 and BRtL-2, were identified as Bacillus amyloliquefaciens and B. subtilis,
      respectively, based on the 16S rRNA gene sequencing. These results suggest that
      endophytic Bacillus species from native medicinal plants have great potential for
      being used as natural plant growth promoter and biopesticides in sustainable crop
      production.

PMID- 29652670
TI  - Multi-layer imager design for mega-voltage spectral imaging.
AB  - The architecture of multi-layer imagers (MLIs) can be exploited to provide
      megavoltage spectral imaging (MVSPI) for specific imaging tasks. In the current
      work, we investigated bone suppression and gold fiducial contrast enhancement as
      two clinical tasks which could be improved with spectral imaging. A method based
      on analytical calculations that enables rapid investigation of MLI component
      materials and thicknesses was developed and validated against Monte Carlo
      computations. The figure of merit for task-specific imaging performance was the
      contrast-to-noise ratio (CNR) of the gold fiducial when the CNR of bone was equal
      to zero after a weighted subtraction of the signals obtained from each MLI layer.
      Results demonstrated a sharp increase in the CNR of gold when the build-up
      component or scintillation materials and thicknesses were modified. The potential
      for low-cost, prompt implementation of specific modifications (e.g. composition
      of the build-up component) could accelerate clinical translation of MVSPI.

PMID- 29652671
TI  - Exploring proximity effects and large depth of field in helium ion beam
      lithography: large-area dense patterns and tilted surface exposure.
AB  - Helium ion beam lithography (HIL) is an emerging nanofabrication technique. It
      benefits from a reduced interaction volume compared to that of an electron beam
      of similar energy, and hence reduced long-range scattering (proximity effect),
      higher resist sensitivity and potentially higher resolution. Furthermore, the
      small angular spread of the helium ion beam gives rise to a large depth of field.
      This should enable patterning on tilted and curved surfaces without the need of
      any additional adjustments, such as laser-auto focus. So far, most work on HIL
      has been focused on exploiting the reduced proximity effect to reach single-digit
      nanometer resolution, and has thus been concentrated on single-pixel exposures
      over small areas. Here we explore two new areas of application. Firstly, we
      investigate the proximity effect in large-area exposures and demonstrate HIL's
      capabilities in fabricating precise high-density gratings on large planar
      surfaces (100 MUm * 100 MUm, with pitch down to 35 nm) using an area dose for
      exposure. Secondly, we exploit the large depth of field by making the first HIL
      patterns on tilted surfaces (sample stage tilted 45 degrees ). We demonstrate a
      depth of field greater than 100 MUm for a resolution of about 20 nm.

PMID- 29652672
TI  - Early discontinuation of prasugrel or clopidogrel in acute coronary syndromes:
      insights from the TRILOGY ACS trial.
AB  - BACKGROUND: In the Targeted Platelet Inhibition to Clarify the Optimal Strategy
      to Medically Manage Acute Coronary Syndromes (TRILOGY ACS) trial of patients with
      non-ST-segment elevation acute coronary syndrome managed medically without
      revascularization, treated with prasugrel versus clopidogrel for less than or
      equal to 30 months after index acute coronary syndrome, post-hoc analyses showed
      a divergence of treatment effect in favor of prasugrel after 12 months. Potential
      influential factors, including a potential late treatment effect after early
      study drug discontinuation in the intention-to-treat analysis, have not been
      explored. PATIENTS AND METHODS: We carried out an exploratory, post-hoc analysis
      of 1436 patients who received at least one dose of the study drug and
      discontinued the drug 7-365 days after randomization. Kaplan-Meier event rates
      were evaluated starting at the landmark timepoint of study discontinuation
      through 2 years of follow-up, and were compared between prasugrel and
      clopidogrel. RESULTS: The unadjusted rates of the primary composite endpoint of
      cardiovascular death, myocardial infarction, or stroke were 20.1 versus 24.4% in
      the prasugrel versus clopidogrel groups (log-rank P=0.069). Similar findings were
      observed for cardiovascular death (13.3 vs. 18.0%, log-rank P=0.022), and
      cardiovascular death or myocardial infarction (19.3 vs. 23.3%, log-rank P=0.042).
      In multivariable analyses, there were no significant differences in the adjusted
      risk of these outcomes between the prasugrel and clopidogrel groups. CONCLUSION:
      In this hypothesis-generating analysis, high rates of ischemic events were
      observed after study drug discontinuation, with a lower frequency of events among
      patients treated with prasugrel versus clopidogrel that did not persist after
      multivariable adjustment. This analysis highlights the complexities of
      ascertaining downstream effects of antithrombotic therapies after drug
      discontinuation.

PMID- 29652673
TI  - Inflammation and coronary artery disease: from pathophysiology to Canakinumab
      Anti-Inflammatory Thrombosis Outcomes Study (CANTOS).
AB  - The worldwide prevalence of cardiovascular disease in general and atherosclerotic
      coronary artery disease in particular is a health and economic concern of
      unparalleled proportion. Despite a long history of astute observations beginning
      in 1575 made by Fallopius, followed by those of von Rokatansky, Virchow, Osler,
      and Ross, and incremental knowledge of the pathobiology of atherosclerosis to
      include varying stages of inflammation, response to internally and externally
      mediated vascular injury, and impaired homeostasis, gaps in the field's
      understanding persist. Here, we summarize the current scope of the problem for
      coronary artery disease, emerging constructs in its pathobiology and common
      clinical phenotypes, potentially useful biomarkers, clinical trials designed
      specifically to test the 'inflammation hypothesis' of disease, and the interface
      of pathobiology and precision medicine as a foundation for diagnosis, management,
      and future advances in the diagnosis, prognosis, natural history, prevention, and
      optimal management.

PMID- 29652674
TI  - Analysis of Intercanine Distance and Dimensional Changes in Bite Marks on
      Foodstuffs Using Cone Beam Computed Tomography.
AB  - Bite marks on foodstuff at the crime scene provide a 3-dimensional imprint of the
      suspect's dentition. The bite mark analysis can provide useful evidences, leading
      to the inclusion or exclusion of the individual under investigation. This study
      was designed to assess bite marks on various common foodstuffs (chocolate, apple,
      chewing gum, cheese) for different time intervals using cone beam computed
      tomography (CBCT) to evaluate the dimensional changes in the foodstuffs. Analysis
      of variance test was used to compare the bite marks measured using CBCT in
      maxillary and mandibular arches with significance set at P < 0.05. The results
      show that teeth can transfer their characteristics to the bitten foodstuffs. The
      highest accuracy for comparative bite mark analysis was observed in chocolate
      followed by cheese, chewing gum, and apple. The CBCT-assisted analysis of bite
      marks is a nondestructive, accurate, and efficient method. The CBCT documentation
      has no distortion artifacts, and subsequent analysis in 3-dimensional space is
      possible.

PMID- 29652676
TI  - Immune tolerance induction rescue with turoctocog-alfa in a poor risk haemophilia
      A inhibitor young child: the history of a success.
AB  - : The development of alloantibodies against the replacement of Factor VIII
      (FVIII) is the major complication in haemophilia A treatment. The gold standard
      to eradicate inhibitors is the immune tolerance induction (ITI), but in some
      cases it fails requiring another immune tolerance, defined ITI rescue (ITI-R),
      using a different concentrate, even though it is still debated. We report a
      successful case of a poor risk (titre of inhibitor at start of ITI > 10 BU/ml,
      peak titre on ITI > 200 BU/ml, >2 years since the inhibitor diagnosis)
      haemophilia A child treated with a high-dose regimen (200 UI/kg/day) turoctocog
      alfa after a failed first-line ITI with octocog-alfa lasting 29 months. At 22
      months of ITI-R, the inhibitor titre was undetectable, the FVIII recovery was
      74%, of the expected level and the FVIII half-life more than 7 h. A complete
      successful ITI-R was then achieved with turoctocog-alfa.

PMID- 29652675
TI  - An intronic mutation c.6430-3C>G in the F8 gene causes splicing efficiency and
      premature termination in hemophilia A.
AB  - : Hemophilia A is a bleeding disorder caused by coagulation factor VIII protein
      deficiency or dysfunction, which is classified into severe, moderate, and mild
      according to factor clotting activity. An overwhelming majority of missense and
      nonsense mutations occur in exons of F8 gene, whereas mutations in introns can
      also be pathogenic. This study aimed to investigate the effect of an intronic
      mutation, c.6430-3C>G (IVS22-3C>G), on pre-mRNA splicing of the F8 gene. We
      applied DNA and cDNA sequencing in a Chinese boy with hemophilia A to search if
      any pathogenic mutation in the F8 gene. Functional analysis was performed to
      investigate the effect of an intronic mutation at the transcriptional level.
      Human Splicing Finder and PyMol were also used to predict its effect. We found
      the mutation c.6430-3C>G (IVS22-3C>G) in the F8 gene in the affected boy, with
      his mother being a carrier. cDNA from the mother and pSPL3 splicing assay showed
      that the mutation IVS22-3C>G results in a two-nucleotide AG inclusion at the 3'
      end of intron 22 and leads to a truncated coagulation factor VIII protein, with
      partial loss of the C1 domain and complete loss of the C2 domain. The in-silico
      tool predicted that the mutation induces altered pre-mRNA splicing by using a
      cryptic acceptor site in intron 22. The IVS22-3C>G mutation was confirmed to
      affect pre-mRNA splicing and produce a truncated protein, which reduces the
      stability of binding between the F8 protein and von Willebrand factor carrier
      protein due to the loss of an interaction domain.

PMID- 29652677
TI  - Ontology Development for Patient Education Documents Using a Professional- and
      Patient-Oriented Delphi Method.
AB  - Written patient education materials are essential to motivate and help patients
      to participate in their own care, but the production and management of a large
      collection of high-quality and easily accessible patient education documents can
      be challenging. Ontologies can aid in these tasks, but the existing resources are
      not directly applicable to patient education. An ontology that models patient
      education documents and their readers was constructed. The Delphi method was used
      to identify a compact but sufficient set of entities with which the topics of
      documents may be described. The preferred terms of the entities were also
      considered to ensure their understandability. In the ontology, readers may be
      characterized by gender, age group, language, and role (patient or professional),
      whereas documents may be characterized by audience, topic(s), and content, as
      well as the time and place of use. The Delphi method yielded 265 unique document
      topics that are organized into seven hierarchies. Advantages and disadvantages of
      the ontology design, as well as possibilities for improvements, were identified.
      The patient education material ontology can enhance many applications, but
      further development is needed to reach its full potential.

PMID- 29652678
TI  - Using Hourly Time-Outs and a Standardized Tool to Promote Team Communication,
      Medical Record Documentation, and Patient Satisfaction During Second-Stage Labor.
AB  - BACKGROUND: During labor, effective communication and collaboration among the
      healthcare team is critical for patient safety; however, there is currently no
      standard for communication and documentation of the plan of care as agreed upon
      by healthcare team members and the woman in labor. OBJECTIVES: The goal of this
      project was to increase consistency in communication and collaboration between
      clinicians and laboring women during second-stage labor. METHODS: An hourly "time
      out" meeting of all healthcare team members was initiated for all women during
      second-stage labor. A documentation tool was implemented to ensure regular and
      clear communication between the clinical team and laboring women. Data were
      collected via medical review of cases of second-stage labor lasting more than 2
      hours (n = 21 in the pre-implementation group; n = 39 for 3 months
      postimplementation; and n = 468 patients for 2 years post-implementation).
      Surveys were conducted of the clinical team (n = 40) and patients (n = 28).
      RESULTS: Following implementation, documented agreement of the plan of care
      increased from 14.3% before the project to 82.1% 3 months after implementation
      and remained at 81.6% 2 years after implementation. All nurses who participated
      in the survey reported a clear understanding of how and when to complete
      necessary medical record documentation during second-stage labor. The providers
      viewed the project favorably. Most women (92.9%) reported satisfaction with their
      experience. This project enhanced collaborative communication between members of
      the clinical team and laboring women and improved patient satisfaction. The
      improvements were sustainable over a 2-year period.

PMID- 29652679
TI  - Comparison of Static and Dynamic Balance at Different Levels of Sport Competition
      in Professional and Junior Elite Soccer Players.
AB  - Jadczak, L, Grygorowicz, M, Dzudzinski, W, and Sliwowski, R. Comparison of static
      and dynamic balance at different levels of sport competition in professional and
      junior elite soccer players. J Strength Cond Res XX(X): 000-000, 2018-The purpose
      of this study was to compare body balance control and balance recovery strategies
      of professional football players, representing various sports levels in static
      (eyes open, eyes closed) and dynamic conditions, both on the dominant and
      nondominant leg. Three groups of professional and junior elite soccer players
      were investigated: a PRO group (n = 52), a U-21 group (n = 55), and a U-19 group
      (n = 47). The study of body balance control was performed using a Delos Postural
      Proprioceptive System measurement tool. The analysis of the results showed an
      effect of group (p < 0.01) and leg significance (p < 0.95) in the dynamic test.
      Three-way analysis of variance (3 [group] * 2 [leg] * 2 [eyes]) of static test
      data showed that the main effect of eyes (p < 0.0001), group (p < 0.0001), and
      leg (p = 0.0092) and the 2-way interaction of eyes * group (p = 0.0003) were
      significant. To represent statistical significance, the cutoff value was set to
      be p <= 0.005 for all measures. Our results indicate the importance of evaluation
      and monitoring of dynamic and static balance on both legs, which allows for a
      comprehensive comparison of body balance control and the balance recovery
      strategy depending on the represented sport level. Our study indicates that the
      higher the sport level of football players (the PRO group), the better their
      balance, which may indirectly contribute to the prevention of injuries and more
      effective performance of any actions directly related to the game.

PMID- 29652680
TI  - Impact of intra-operative fluid and noradrenaline administration on early
      postoperative renal function after cystectomy and urinary diversion: A
      retrospective observational cohort study.
AB  - BACKGROUND: The use of noradrenaline to enable a restrictive approach to intra
      operative fluid therapy to avoid salt and water overload has gained increasing
      acceptance. However, concerns have been raised about the impact of this approach
      on renal function. OBJECTIVES: To identify risk factors for acute kidney injury
      (AKI) in patients undergoing cystectomy with urinary diversion and determine
      whether administration of noradrenaline and intra-operative hydration regimens
      affect early postoperative renal function. DESIGN: Retrospective observational
      cohort study. SETTING: University hospital, from 2007 to 2016. PATIENTS: A total
      of 769 consecutive patients scheduled for cystectomy and urinary diversion. Those
      with incomplete data and having pre-operative haemodialysis were excluded. MAIN
      OUTCOME MEASURES: AKI was defined as a serum creatinine increase of more than 50%
      over 72 postoperative hours. Multiple logistic regression analysis was performed
      to model the association between risk factors and AKI. RESULTS: Postoperative AKI
      was diagnosed in 86/769 patients (11.1%). Independent predictors for AKI were the
      amount of crystalloid administered (odds ratio (OR) 0.79 [95% confidence interval
      (CI), 0.68 to 0.91], P = 0.002), antihypertensive medication (OR 2.07 [95% CI,
      1.25 to 3.43], P = 0.005), pre-operative haemoglobin value (OR 1.02 [95% CI, 1.01
      to 1.03], P = 0.010), duration of surgery (OR 1.01 [95% CI, 1.00 to 1.01], P =
      0.002), age (OR 1.32 [95% CI, 1.44 to 1.79], P = 0.002) but not the
      administration of noradrenaline (OR 1.09 [95% CI, 0.94 to 1.21], P = 0.097).
      Postoperative AKI was associated with longer hospital stay (18 [15 to 22] vs. 16
      [15 to 19] days; P = 0.035) and a higher 90-day major postoperative complication
      rate (41.9 vs. 27.5%; P = 0.002). CONCLUSION: Noradrenaline administration did
      not increase the risk for AKI. A too restrictive approach to administration of
      crystalloids was associated with an increased risk for AKI, particularly in older
      patients, those receiving antihypertensive medication, and those whose surgery
      was prolonged. As AKI was associated with longer hospital stay and increased
      postoperative morbidity, these observations should be taken into account to
      improve outcome when addressing peri-operative fluid management. TRIAL
      REGISTRATION: Not applicable.

PMID- 29652681
TI  - Direct Ultrasound of the Pulmonary Artery Helps Diagnose a Rare Cause of Right
      Ventricular Failure After Heart Transplantation: A Case Report.
AB  - Pulmonary artery anastomosis stenosis is a rare cause of right ventricular
      failure after orthotopic heart transplantation. In this case report, direct
      ultrasound of the pulmonary artery helped diagnose stenosis at a location not
      visible on transesophageal echocardiography or even with standard epicardial
      ultrasound views. It is important to evaluate all vascular anastomoses after
      heart or lung transplantation because surgical revision of these lesions is
      facile, but if left undiagnosed, significant morbidity or mortality is likely.

PMID- 29652682
TI  - Kratom, an Emerging Drug of Abuse: A Case Report of Overdose and Management of
      Withdrawal.
AB  - Kratom is an herb indigenous to Southeast Asia with psychoactive opioid
      compounds, often used as a treatment for chronic pain or opiate withdrawal
      symptoms. It is legally and readily available via Internet sales and has been
      identified as an emerging drug of abuse in the United States. Kratom use has been
      associated with psychosis, seizures, and even death. At lower doses, kratom acts
      as a stimulant, while at higher doses, it produces analgesia and euphoria. Here,
      we describe the successful management of kratom overdose and withdrawal in a
      young man with negative toxicology screens.

PMID- 29652683
TI  - A Case Report of Recurrent Severe Peripartum Cardiomyopathy Complicated by Factor
      V Leiden and Multiple Endocrine Neoplasia Type 1: A Management Conundrum.
AB  - Cardiovascular disease is the leading cause of peripartum death in the United
      States during pregnancy. The presence of concomitant diagnoses may complicate or
      conflict with the management of the primary cardiovascular diagnosis and further
      complicate pregnancy and delivery. We describe the management of a 29-year-old,
      gravida 5, para 1 woman with severe peripartum cardiomyopathy during this and a
      previous pregnancy complicated by multiple endocrine neoplasia type and factor V
      Leiden thrombophilia, limiting therapeutic options and contributing to
      considerable perioperative management challenges.

PMID- 29652684
TI  - Biphasic Cuirass Ventilation During Anesthesia for Tracheobronchial Stent
      Insertion or Removal by a Rigid Bronchoscope: A Case Report.
AB  - Airway management and ventilation during a tracheobronchial stenting procedure
      are challenging given that mandatory positive pressure ventilation cannot be
      fully achieved while using a rigid bronchoscope due to leakage from the scope
      tip. Biphasic cuirass ventilation is a negative pressure ventilation method using
      an external cuirass fitted to the anterior chest, which could assist in
      spontaneous breathing and ventilation support. We report 3 successful anesthesia
      cases in which we could maintain adequate ventilation and oxygenation, supported
      by biphasic cuirass ventilation, in patients undergoing tracheobronchial stent
      placement or removal procedures using rigid bronchoscopy.

PMID- 29652685
TI  - Blood Patch in a Jehovah's Witness: Case Report of a Novel Arterial-to-Epidural
      Closed-Circuit Technique.
AB  - Jehovah's Witness patients have unique perioperative challenges involving blood
      products. We describe the use of a novel method to maintain a closed circuit
      between a Jehovah's Witness patient's arterial blood and the epidural space while
      performing a blood patch for postdural puncture headache. Previously described
      methods have utilized venous catheters to maintain a closed circuit between the
      body and the epidural space. This is the first report we are aware of that
      utilizes a closed-circuit arterial blood supply to create an epidural blood patch
      in a Jehovah's Witness patient.

PMID- 29652686
TI  - Massive Macroglossia After Posterior Cranial Fossa Surgery: A Case Report.
AB  - A 16-year-old boy with Chiari 1 malformation presented for an elective
      suboccipital craniectomy and C1 laminectomy. His intraoperative course was
      uneventful. At the conclusion of the procedure, he met extubation criteria and
      followed commands. After extubation, he developed progressive upper airway
      obstruction and became obtunded. He was reintubated via videolaryngoscopy, which
      showed edema not only to the tongue, but also to the posterior pharynx and
      blisters over the vocal folds and epiglottis. The patient was transferred to the
      pediatric intensive care unit intubated and sedated. This report describes the
      clinical course of his massive macroglossia and discusses short- and long-term
      management.

PMID- 29652687
TI  - Ultrasound-Guided Transversalis Fascia Plane Block: An Alternative Approach for
      Anesthesia in Inguinal Herniorrhaphy: A Case Report.
AB  - Ultrasound (US)-guided transversalis fascia plane block (TFPB) was first
      described by Hebbard as a technique for blockade of T12-L1 nerves. Although this
      technique appears similar to the quadratus lumborum 1 block, the point of
      injection is more caudal and anterior, specifically targeting ilioinguinal and
      iliohypogastric nerves. There are only few published data on US-guided TFPB
      demonstrating effective postoperative analgesia in iliac crest bone graft
      harvesting. We report the use of US-guided TFPB in a patient undergoing inguinal
      herniorrhaphy. Our experience suggests that this technique could represent a
      viable alternative to general anesthesia and standard regional techniques for
      inguinal hernia repair.

PMID- 29652688
TI  - Acute Coronary Artery Thrombus After Tranexamic Acid During Total Shoulder
      Arthroplasty in a Patient With Coronary Stents: A Case Report.
AB  - Tranexamic acid (TXA), an antifibrinolytic, is routinely used to decrease
      transfusion rates in total joint replacement surgery. While recent publications
      have indicated a low risk of TXA-associated thromboembolic events in this
      orthopedic population, few studies specifically address the safety of TXA
      administration in high-risk patients. We present a case of acute coronary
      thrombus requiring emergent intervention in a patient with indwelling coronary
      stents who underwent shoulder arthroplasty with TXA administration.

PMID- 29652689
TI  - Postoperative Harlequin Syndrome: Case Report of a Rare but Clinically Striking
      Condition.
AB  - We present a case of a 2-year-old boy who underwent thoracoscopic resection of a
      left paraspinal mediastinal mass and developed Harlequin syndrome
      postoperatively. Harlequin syndrome is a rare neurological condition
      characterized by unilateral hyperhidrosis and erythema of the head and neck. Our
      discussion highlights this condition and other differential diagnoses that may
      present similarly in the postoperative period.

PMID- 29652690
TI  - ENDOPHTHALMITIS AFTER PARS PLANA VITRECTOMY: Efficacy of Intraoperative
      Subconjunctival Antibiotics.
AB  - PURPOSE: To examine rates of acute infectious endophthalmitis after pars plana
      vitrectomy (PPV) in eyes that received intraoperative subconjunctival antibiotics
      versus eyes that did not. METHODS: A retrospective, nonrandomized, comparative
      case series of 18,886 consecutive cases of transconjunctival 23-, 25-, and 27
      gauge PPV over a 5-year period was performed. The impact of prophylactic
      intraoperative subconjunctival antibiotics on the development of acute infectious
      postoperative endophthalmitis was examined. RESULTS: Of 18,886 cases of PPV,
      14,068 (74.5%) received intraoperative subconjunctival antibiotics, whereas 4,818
      (25.5%) did not. Sixteen cases (0.085%, 1/1,176) of post-PPV endophthalmitis were
      identified. The incidence of endophthalmitis in eyes that received
      subconjunctival antibiotics was 0.078% (11/14,068 cases, 1/1,282), whereas the
      incidence in those that did not receive subconjunctival antibiotics was 0.10%
      (5/4,818 cases, 1/1,000). No statistically significant difference was identified
      in the incidence of endophthalmitis between those that received subconjunctival
      antibiotics and those that did not (P = 0.598). Microbial culture was performed
      in 11 cases with 6 culture-positive cases (5/8 cases that received
      subconjunctival antibiotics and 1/3 cases that did not). CONCLUSION: Prophylactic
      subconjunctival antibiotics were not associated with a significantly reduced rate
      of post-PPV endophthalmitis. With consideration of emerging multidrug-resistant
      bacteria, routine prophylactic subconjunctival antibiotics may not be justified.

PMID- 29652691
TI  - VISUAL ACUITY IN PSEUDOXANTHOMA ELASTICUM.
AB  - PURPOSE: To assess the age-specific proportion of visual impairment in patients
      with pseudoxanthoma elasticum (PXE) and to compare this with foveal abnormality
      and similar data of late age-related macular degeneration patients. METHODS:
      Cross-sectional data of 195 patients with PXE were reviewed, including best
      corrected visual acuity and imaging. The World Health Organisation criteria were
      used to categorize bilateral visual impairment. These results were compared with
      similar data of 131 patients with late age-related macular degeneration from the
      Rotterdam study. RESULTS: Overall, 50 PXE patients (26.0%) were visually
      impaired, including 21 (11%) with legal blindness. Visual functioning declined
      with increasing age. In patients older than 50 years, 37% was visually impaired
      and 15% legally blind. Foveal choroidal neovascularization was found in 84% of
      eyes with a best-corrected visual acuity lower than 20/70 (0.30) and macular
      atrophy in the fovea in 16%. In late age-related macular degeneration patients,
      40% were visually impaired and 13% legally blind. Visual impairment started
      approximately 20 years later as compared with PXE patients. CONCLUSION: Visual
      impairment and blindness are frequent in PXE, particularly in patients older than
      50 years. Although choroidal neovascularization is associated with the majority
      of vision loss, macular atrophy is also common. The proportion of visual
      impairment in PXE is comparable with late age-related macular degeneration but
      manifests earlier in life.

PMID- 29652692
TI  - Potential Roles of Vascular Endothelial Growth Factor During Skeletal Muscle
      Hypertrophy.
AB  - Vascular endothelial growth factor (VEGF) deletion in adult mouse muscle fibers
      contributes to impaired contractile and muscular adaptations to a hypertrophic
      stimulus suggesting a critical role in adult muscle growth. This review explores
      the hypothesis that VEGF is essential for adult muscle growth by impacting
      inflammatory processes, satellite-endothelial cell interactions, and contractile
      protein accumulation by functioning within known hypertrophic signaling pathways
      including insulin-like growth factor-1 (IGF-1-Akt) and Wnt-beta-catenin.

PMID- 29652693
TI  - Perspectives for Progress: Concepts About V[Combining Dot Above]O2max and
      Trainability Are Context Dependent.
AB  - Some individuals show little or no increase in V[Combining Dot Above]O2max in
      response to training programs consistent with public health guidelines. However,
      results from studies using more intense programs challenge the concept that some
      humans have limited trainability. We explore the implications of these divergent
      observations on the biology of trainability and propose a new set of twin studies
      to explore them.

PMID- 29652694
TI  - Perspectives for Progress -- Performance Limitations in Heart Transplant
      Recipients.
AB  - We hypothesize that the reduced peak aerobic power (peak VO2) following heart
      transplantation (HT) is due to impaired cardiovascular and skeletal muscle
      function, and its improvement with short-term (<=1 year) exercise training is
      primarily due to favorable skeletal muscle adaptations. Further, the increased
      peak VO2 with long-term (>2 years) training is primarily mediated by cardiac
      (sympathetic) reinnervation.

PMID- 29652696
TI  - In Reply.

PMID- 29652697
TI  - Recent Increases in the U.S. Maternal Mortality Rate: Disentangling Trends From
      Measurement Issues.

PMID- 29652695
TI  - The Microvasculature and Skeletal Muscle Health in Aging.
AB  - Aging and aging-related declines in physical activity are associated with
      physical and metabolic impairments. Skeletal muscle capillarization is reduced in
      sedentary older adults, may contribute to impairments in skeletal muscle, and is
      modifiable by exercise training. This article examines the hypothesis that
      preservation of skeletal muscle capillarization is essential to maintain
      metabolism, fitness, and function with aging.

PMID- 29652698
TI  - Student Self-evaluation After Nursing Examinations: That's a Wrap.
AB  - Examination wrappers are a self-evaluation tool that uses metacognition to help
      students reflect on test performance. After examinations, rather than focus on
      points earned, students learn to self-identify study strategies and recognize
      methods of test preparation. The purpose of the study was to determine if the use
      of an examination wrapper after each test would encourage students to self
      evaluate performance and adjust study strategies. A total of 120 undergraduate
      nursing students completed self-evaluations after each examination, which were
      analyzed using content analysis. Three general patterns emerged from student self
      evaluation: effective and ineffective study strategies, understanding versus
      memorization of content, and nurse educator assistance.

PMID- 29652699
TI  - Impact of the Glymphatic System on the Kinetic and Distribution of Gadodiamide in
      the Rat Brain: Observations by Dynamic MRI and Effect of Circadian Rhythm on
      Tissue Gadolinium Concentrations.
AB  - OBJECTIVES: The glymphatic system is a recently hypothesized waste clearance
      system of the brain in which perivascular space constitutes a pathway similar to
      the lymphatic system in other body regions. Sleep and anesthesia are reported to
      influence the activity of the glymphatic system. Because rats are nocturnal
      animals, the glymphatic system is expected to be more active during the day. We
      attempted to elucidate the influence of the glymphatic system for intravenously
      injected gadodiamide in the rat brain by 2 experiments. One was a magnetic
      resonance imaging (MRI) experiment to evaluate the short-term dynamics of signal
      intensity changes after gadodiamide administration. The other was a
      quantification experiment to evaluate the concentration of retained gadolinium
      within the rat brain after repeated intravenous administration of gadodiamide at
      different times of day and levels of anesthesia. MATERIALS AND METHODS: The
      imaging experiment was performed on 6 rats that received an intravenous injection
      of gadodiamide (1 mmol/kg) and dynamic MRI for 3 hours at 2.4-minute intervals.
      The time course of the signal intensity changes was evaluated for different brain
      structures. The tissue quantification experiment was performed on 24 rats divided
      into 4 groups by injection time (morning, late afternoon) and anesthesia (none,
      short, long) during administration. All animals received gadodiamide (1.8
      mmol/kg, 8 times over 2 weeks). Gadolinium concentration of dissected brain
      tissues was quantified 5 weeks after the last administration by inductively
      coupled plasma mass spectrometry. RESULTS: In the imaging experiment, muscle and
      the fourth ventricle showed an instantaneous signal intensity increase
      immediately after gadodiamide injection. The signal curve of the cerebral cortex
      and deep cerebellar nuclei reached the peak signal intensity later than the
      fourth ventricle but earlier than that of the prepontine cistern. In the
      gadolinium quantification experiment, the concentration in the group with the
      morning injection showed a significantly lower concentration than the late
      afternoon injection group. The lowest tissue gadolinium concentrations were found
      in the groups injected in the morning during long anesthesia. CONCLUSIONS:
      Instantaneous transition of gadodiamide from blood to cerebrospinal fluid was
      indicated by dynamic MRI. The gadodiamide distribution to the cerebral cortex and
      deep cerebellar nuclei seemed to depend on both blood flow and cerebrospinal
      fluid. This confirms previous studies indicating that the cerebrospinal fluid is
      one potential pathway of gadolinium-based contrast agent entry into the brain.
      For the distribution and clearance of the gadodiamide from brain tissue,
      involvement of the glymphatic system seemed to be indicated in terms of the
      influence of sleep and anesthesia.

PMID- 29652700
TI  - Overall Disability Sum Score for Clinical Assessment of Neurological Involvement
      in Eosinophilic Granulomatosis With Polyangiitis.
AB  - AIM: The aim of this study was to verify the application of Overall Disability
      Sum Score (ODSS) for standardized clinical assessment of neurological involvement
      in patients with eosinophilic granulomatosis with polyangiitis (EGPA) and its
      correlation with treatment response and long-term outcomes. METHODS: Consecutive
      EGPA patients referred to our tertiary vasculitis center were retrospectively
      evaluated. Patients' neurological damage and disability were systematically
      assessed with Vasculitis Damage Index and ODSS. RESULTS: Fifty EGPA patients were
      included in the study with a median follow-up of 75 months (9-180 months). Twenty
      five (50%) developed peripheral neuropathy, 17 (68%) presented mononeuritis
      multiplex, whereas 8 (32%) had symmetric polyneuropathy. Patients with
      neurological involvement were older (56.3 +/- 13.4 vs. 44.4 +/- 12.1 years, P <
      0.0009), more frequently antineutrophil cytoplasmic antibody positive (48% vs.
      16%, P = 0.015), and were more likely to have renal involvement (24% vs. 0%, P =
      0.022). An early clinical response to therapy was observed within 6 months of
      treatment, resulting in a significant decrease in ODSS, which fell from the
      baseline value of 4.2 +/- 2.4 to 2.9 +/- 1.5 (P = 0.0001), whereas only a slow
      decreasing pattern was noted over the long-term period. However, all subjects
      developed neurological impairment and disability despite remission from active
      vasculitis. Patients with ODSS of greater than 3 at baseline (n = 13 [52%])
      retained a higher score at the last examination (P < 0.001), predicting a low
      therapeutic response. Furthermore, ODSS of greater than 3 was found associated
      with more neurological relapses (53.8% vs. 0%, P = 0.027). CONCLUSION: Overall
      Disability Sum Score could be a rapid, simple, reliable instrument to evaluate
      the severity of disability and nerve damage due to neurological involvement
      caused by vasculitis and to predict, at presentation, improvement and risk of
      neurological worsening.

PMID- 29652701
TI  - Leukocytoclastic Vasculitis Concurrent With Bullous Systemic Lupus Erythematosus
      Manifesting Striking Wood-Grain and Wi-Fi Sign-like Purpuric Lesions.

PMID- 29652702
TI  - Microwave Radiometry-Derived Thermal Changes of Small Joints as Additional
      Potential Biomarker in Rheumatoid Arthritis: A Prospective Pilot Study.
AB  - OBJECTIVE: A prospective pilot study was performed using microwave radiometry
      (MR), a noninvasive method detecting in-depth tissue temperature, to evaluate
      whether temperature-of-small-joint-derived scores correlate to parameters
      commonly used to assess disease activity in rheumatoid arthritis (RA). METHODS:
      Ten patients with active, untreated RA underwent clinical and laboratory
      assessments and joint ultrasound and MR of hand and foot small joints at baseline
      and at 15, 30, and 90 days after treatment onset. Mixed-model analysis for
      repeated measures was used to compare patient characteristics in sequential
      visits. Twenty age- and sex-matched healthy individuals served as control
      subjects. RESULTS: Using 1248 MR-derived separate recordings from patients'
      joints, several thermoscores involving different joint combinations were created.
      When compared with clinical and ultrasound data, the best performing thermoscore
      involved temperatures of 16 joints (second to fifth metacarpal and proximal
      interphalangeal joints, bilaterally). This thermoscore correlated to the 28-joint
      Disease Activity Score-C-reactive protein, tender and swollen joint counts,
      patient's visual analog scale (all P <= 0.02), and the standard 7-joint
      ultrasound score (P < 0.03) and could also discriminate patients in high (mean,
      9.2 [SD, 5.6]) or moderate (7.1 [SD, 3.5]) versus low disease activity/remission
      (4.2 [SD, 1.8]) (P <= 0.01) or healthy subjects (5.0 [SD, 1.7]) (P = 0.002).
      CONCLUSIONS: Microwave radiometry-derived increased in-depth temperature
      indicative of local inflammation of small joints may serve as an additional
      biomarker in RA. Optimization of MR-based methods may result in objective
      assessments of RA disease activity in clinical practice.

PMID- 29652703
TI  - Secondary Hypertrophic Osteoarthropathy Associated With Pediatric Primary Lung
      Squamous Cell Carcinoma.

PMID- 29652704
TI  - The Urgency of Now: Attacking the Sepsis Crisis.

PMID- 29652706
TI  - Care of the Critically Ill Cirrhotic: It Is Not a Losing Battle.

PMID- 29652705
TI  - Is Procalcitonin-Guided Therapy Associated With Beneficial Outcomes in Critically
      Ill Patients With Sepsis?

PMID- 29652707
TI  - Denied and Delayed Care: The Synergy Between the Emergency Department and the
      ICU.

PMID- 29652708
TI  - Telemedicine Application to Progressive Care Units: A New Role for Telemedicine.

PMID- 29652709
TI  - All Organ Dysfunctions Are Equal...But Some Are More Equal Than Others.

PMID- 29652710
TI  - Chest Radiography for Diagnosing Acute Respiratory Distress Syndrome-Fishing in
      the Dark?

PMID- 29652711
TI  - Readmissions as a Quality Metric: Ready for Prime Time?

PMID- 29652712
TI  - Changing Cardiopulmonary Resuscitation to Cardiocerebral Resuscitation: The
      Reason We Push Hard and Fast.

PMID- 29652714
TI  - Growing Evidence: Dysautoregulation May Trigger Ischemic Deficit After
      Subarachnoid Hemorrhage.

PMID- 29652713
TI  - "Size Matters" in Regard to Acute Respiratory Distress Syndrome Case Volume and
      Mortality!

PMID- 29652715
TI  - Is "Moderate" the Correct Adjective?

PMID- 29652716
TI  - Help is Helpful.

PMID- 29652717
TI  - Time for Targeted Therapies in Acute Respiratory Distress Syndrome? Understanding
      Every Single Piece of the Puzzle.

PMID- 29652718
TI  - Translational Research: The Model Matters.

PMID- 29652719
TI  - Vasopressors During Cardiopulmonary Resuscitation. A Network Meta-Analysis of
      Randomized Trials.
AB  - OBJECTIVES: Several randomized controlled trials have compared adrenaline
      (epinephrine) with alternative therapies in patients with cardiac arrest with
      conflicting results. Recent observational studies suggest that adrenaline might
      increase return of spontaneous circulation but worsen neurologic outcome. We
      systematically compared all the vasopressors tested in randomized controlled
      trials in adult cardiac arrest patients in order to identify the treatment
      associated with the highest rate of return of spontaneous circulation, survival,
      and good neurologic outcome. DESIGN: Network meta-analysis. PATIENTS: Adult
      patients undergoing cardiopulmonary resuscitation. INTERVENTIONS: PubMed, Embase,
      BioMed Central, and the Cochrane Central register were searched (up to April 1,
      2017). We included all the randomized controlled trials comparing a vasopressor
      with any other therapy. A network meta-analysis with a frequentist approach was
      performed to identify the treatment associated with the highest likelihood of
      survival. MEASUREMENTS AND MAIN RESULTS: Twenty-eight studies randomizing 14,848
      patients in 12 treatment groups were included. Only a combined treatment with
      adrenaline, vasopressin, and methylprednisolone was associated with increased
      likelihood of return of spontaneous circulation and survival with a good
      neurologic outcome compared with several other comparators, including adrenaline.
      Adrenaline alone was not associated with any significant difference in mortality
      and good neurologic outcome compared with any other comparator. CONCLUSIONS: In
      randomized controlled trials assessing vasopressors in adults with cardiac
      arrest, only a combination of adrenaline, vasopressin, and methylprednisolone was
      associated with improved survival with a good neurologic outcome compared with
      any other drug or placebo, particularly in in-hospital cardiac arrest. There was
      no significant randomized evidence to support neither discourage the use of
      adrenaline during cardiac arrest.

PMID- 29652720
TI  - Adverse Effect of RBCs Transfusion: New Transfusion Indicators Are Needed!

PMID- 29652721
TI  - The authors reply.

PMID- 29652722
TI  - Integration of an Abbreviated ICU Cognitive Failure Questionnaire.

PMID- 29652723
TI  - The authors reply.

PMID- 29652724
TI  - Complexities and potential pitfalls of clinical study design and data analysis in
      assisted reproduction.
AB  - PURPOSE OF REVIEW: The purpose of the current review is to describe the common
      pitfalls in design and statistical analysis of reproductive medicine studies. It
      serves to guide both authors and reviewers toward reducing the incidence of
      spurious statistical results and erroneous conclusions. RECENT FINDINGS: The
      large amount of data gathered in IVF cycles leads to problems with multiplicity,
      multicollinearity, and over fitting of regression models. Furthermore, the use of
      the word 'trend' to describe nonsignificant results has increased in recent
      years. Finally, methods to accurately account for female age in infertility
      research models are becoming more common and necessary. SUMMARY: The pitfalls of
      study design and analysis reviewed provide a framework for authors and reviewers
      to approach clinical research in the field of reproductive medicine. By providing
      a more rigorous approach to study design and analysis, the literature in
      reproductive medicine will have more reliable conclusions that can stand the test
      of time.

PMID- 29652725
TI  - Therapeutic strategies involving uterine stem cells in reproductive medicine.
AB  - PURPOSE OF REVIEW: The current review provides an update on recent advances in
      stem cell biology relevant to female reproduction. RECENT FINDINGS: Stem cells
      are undifferentiated cells that often serve as a reservoir of cells to regenerate
      tissue in settings or injury or cell loss. The endometrium has progenitor stem
      cells that can replace all of the endometrium during each menstrual cycle. In
      addition, multipotent endometrial cells replace these progenitor cells when
      depleted. Recruitment of stem cells from outside of the uterus occurs in setting
      of increased demand such as ischemia or injury. Bone marrow-derived multipotent
      stem cells are recruited to the uterus by estrogen or injury-induced expression
      of the chemokine CXCL12. In the setting of overwhelming injury, especially in the
      setting of low estrogen levels, there may be insufficient stem cell recruitment
      to adequately repair the uterus resulting in conditions such as Asherman syndrome
      or other endometrial defects. In contrast, excessive recruitment of stem cells
      underlies endometriosis. Enhanced understanding of stem-cell mobilization,
      recruitment, and engraftment has created the possibility of improved therapy for
      endometrial defects and endometriosis through enhanced manipulation of stem-cell
      trafficking. Further, the normal endometrium is a rich source of multipotent stem
      cells that can be used for numerous applications in regenerative medicine beyond
      reproduction. SUMMARY: A better understanding of reproductive stem-cell biology
      may allow improved treatment of endometrial disease such as Asherman syndrome and
      other endometrial receptivity defects. Inhibiting stem-cell mobilization may also
      be helpful in endometriosis therapy. Finally, endometrial derived multipotent
      stem cells may play a crucial role in cell therapy for regenerative medicine.

PMID- 29652726
TI  - How new technical knowledge impacts clinical approach to infertile patients.

PMID- 29652727
TI  - A Rare Case of Gallbladder and Common Bile Duct Benign Capillary Hemangioma in a
      Toddler.

PMID- 29652728
TI  - Intestinal Microbiota in Hirschsprung Disease.
AB  - OBJECTIVES: The aim of the study was to characterize the microbiota profiles of
      patients with Hirschsprung disease (HD) and to evaluate this in relation to
      postoperative bowel function and the incidence of Hirschsprung-associated
      enterocolitis (HAEC). METHODS: All patients operated on for HD at our center
      between 1987 and 2011 were invited to answer questionnaires on bowel function and
      to participate in a clinical follow-up for laboratory investigations, including
      fecal DNA extraction, fecal calprotectin (FC), and brush border lactase (LCT)
      genotyping. The microbiota compositions of patients with HD were compared with
      those of healthy controls aged between 2 and 7 years. RESULTS: The microbiota
      composition of eligible patients with HD (n = 34; median age 12 [range, 3-25]
      years) differed from the healthy controls (n = 141), showing decreased overall
      microbial richness (P < 0.005). Seventy-seven percent had experienced HAEC.
      Normal maturation of the intestinal flora was not observed, but patients had a
      significantly increased abundance of Proteobacteria among other taxa (P < 0.005)
      resulting in a reduced carbohydrate degradation potential, as predicted by the
      taxonomic composition. Genetic lactase deficiency was present in 17% and did not
      correlate with bowel symptoms. No patients reported active HAEC at the time of
      sampling and FC was within the normal range in all samples. CONCLUSIONS: Patients
      with HD and HAEC had a significantly altered intestinal microbiome compared to
      healthy individuals, characterized by a lack of richness and pathologic
      expansions of taxa, particularly Enterobacteria and Bacilli. Further evaluation
      is needed to identify whether these observations are intrinsic to HD or secondary
      to the recurrent use of antibiotics during early childhood.

PMID- 29652729
TI  - Anorectal Manometry May Reduce the Number of Rectal Suction Biopsy Procedures
      Needed to Diagnose Hirschsprung Disease.
AB  - OBJECTIVES: The aim of the study was to evaluate whether anorectal manometry
      (ARM), which is used to test the rectoanal inhibitory reflex (RAIR), is a safe
      alternative for reducing the number of invasive rectal suction biopsy (RSB)
      procedures needed to diagnose Hirschsprung disease (HD). METHODS: Between 2010
      and 2017, we prospectively collected the ARM results of 105 patients suspected of
      having HD. Following the outcome, the patients either underwent additional tests
      to confirm HD or they were treated conservatively. Primary ARM-based diagnoses
      were compared with the definitive diagnoses based on the pathology reports and/or
      clinical follow-ups. Additionally, we analyzed whether modifications to our ARM
      protocol improved diagnostic accuracy. RESULTS: The sensitivity of ARM and RSB
      was comparable (97% vs 97%). The specificity of ARM, performed according to our
      initial protocol, was significantly lower than that of RSB. After we modified the
      protocol the difference between the specificity of ARM and RSB was no longer
      statistically significant (74% vs 84%, respectively, P = 0.260). The negative
      predictive value of ARM was 100%, while their positive predictive value was
      significantly lower than that of RSB (56% vs 97%, P < 0.001). CONCLUSIONS: ARM is
      a viable screening tool for HD and, provided it is performed properly, it can be
      used to exclude HD with absolute certainty. By contrast, an absent rectoanal
      inhibitory reflex on ARM should always be followed by an RSB to confirm the
      diagnosis of HD. Using ARM as the diagnostic of first choice could reduce the
      number of invasive biopsies.

PMID- 29652730
TI  - Predictors for profound blood pressure response in patients undergoing renal
      sympathetic denervation.
AB  - BACKGROUND: Renal sympathetic denervation (RDN) as treatment for hypertension
      shows highly variable results. Although some patients do not show any blood
      pressure (BP) change and in most patients a BP reduction of at least 5 mmHg can
      be found, some show a reduction at least 20 mmHg. We sought to identify
      predictors for such a profound BP response. METHODS: Profound BP response was
      defined as drop of at least 20 mmHg in daytime systolic ambulatory BP measurement
      (ABPM) 3 months after catheter-based RDN. Three different denervation devices
      were used for RDN, and pulse wave velocity was determined invasively in a
      subgroup of patients. RESULTS: One hundred and ninety consecutive patients were
      included in this analysis. Profound BP response was found in 33 patients.
      Patients with profound BP response were younger (P = 0.04), presented with higher
      baseline ABPM values (P < 0.001), were treated with ultrasound-based RDN and
      received more often a combined treatment with two different diuretics (P = 0.005
      for both). After 3 months, a treatment target of daytime BP less than 135 mmHg
      could be achieved more frequently in patients with profound BP response (61 vs.
      17%, P < 0.001). Age, use of ultrasound RDN, combined diuretic therapy and
      baseline BP independently predicted pronounced BP reduction. A second
      multivariate logistic regression model including pulse wave velocity if available
      identified baseline BP, pulse wave velocity and use of ultrasound denervation as
      independent predictors for profound BP response. CONCLUSION: Younger vascular
      age, higher baseline BP, treatment with ultrasound RDN and combined diuretic
      therapy were found as predictors for a pronounced BP reduction following RDN,
      improving BP control at follow-up.

PMID- 29652732
TI  - Female Athlete Issues for the Team Physician: A Consensus Statement-2017 Update.

PMID- 29652731
TI  - Obesity and cardiovascular risk: a call for action from the European Society of
      Hypertension Working Group of Obesity, Diabetes and the High-risk Patient and
      European Association for the Study of Obesity: part B: obesity-induced
      cardiovascular disease, early prevention strategies and future research
      directions.
AB  - : Obesity predisposes for atrial fibrillation, heart failure, sudden cardiac
      death, renal disease and ischemic stroke, which are the main causes of
      cardiovascular hospitalization and mortality. As obesity and the cardiovascular
      effects on the vessels and the heart start early in life, even from childhood, it
      is important for health policies to prevent obesity very early before the disease
      manifestation emerge. Key roles in the prevention are strategies to increase
      physical exercise, reduce body weight and to prevent or treat hypertension,
      lipids disorders and diabetes earlier and efficiently to prevent cardiovascular
      complications.

PMID- 29652733
TI  - Circumstances and Signs of Approaching Death in Patients With Amyotrophic Lateral
      Sclerosis Undergoing Noninvasive Ventilation in Home Care Settings.
AB  - The purpose of this study was to elucidate the circumstances and symptoms of
      patients with amyotrophic lateral sclerosis (ALS) using noninvasive positive
      pressure ventilation (NPPV) in whom death was approaching, to understand how to
      provide palliative care to dying patients with ALS receiving NPPV management. The
      participants were 6 home visiting nurses who were head or subhead nurses of a
      home visiting nursing agency. Data were collected conducting individual
      semistructured interviews and then group interviews. The results were based on
      qualitative analysis of the circumstances of death and prognostication and showed
      5 categories: difficulties with knowing about approaching death, several signs
      and symptoms of knowing about approaching death, importance of feeling prepared
      and provision of palliative care to die at home, death caused by accident, and
      fate determined by the caregiver's ability. Further research is needed to collect
      rich data about predicting approaching death to improve end-of-life care for NPPV
      dependent ALS patients who do not receive sufficient benefits from NPPV.

PMID- 29652734
TI  - Being Yourself and Thinking About the Future in People With Motor Neuron Disease:
      A Grounded Theory of Self-care Processes.
AB  - INTRODUCTION: Self-care is a crucial aspect in the management of people with
      motor neuron disease (MND). Nurses and healthcare professionals must know the
      processes used by patients in performing self-care to identify problems and help
      them. Decision-making processes, self-understanding, and political and social
      support influence the self-care process in chronic diseases. Little is known
      about the self-care process in MND. OBJECTIVE: The aim of this study was to gain
      insight on the self-care processes in people with MND. METHOD: A grounded theory
      method was chosen for this study. Data from interviews were gathered, and a
      simultaneous comparative analysis was conducted to identify categories and codes.
      RESULTS: Twenty-one people with spinal muscular atrophy and amyotrophic lateral
      sclerosis participated in the study. Five categories were identified as grounded
      in the data. The process starts from "being yourself in the care," and it
      develops thanks to "growing and changing" and with a "thinking about the future"
      approach. "Family role" and "you and who helps you" categories affect the process
      itself. CONCLUSION: The self-care process in people with MND is not seen in a
      daily perspective but changes with the evolution of the disease. For the growing
      patients with MND, changing, accepting and controlling the disease while deciding
      autonomously are the foundations of the process.

PMID- 29652735
TI  - Nursing Sensitive Outcomes After Severe Traumatic Brain Injury: A Nationwide
      Study.
AB  - BACKGROUND: Complications such as infections and conditions after immobilization
      are frequent after severe traumatic brain injury (TBI) due to compromised bodily
      functions. Traditionally, bodily functions are core elements in nursing, and
      therefore nurses in the rehabilitation departments are pivotal in the prevention
      of complications. Hence, the frequency of complications is an indicator of
      nursing care quality, which can be included in nursing-sensitive outcome
      indicators. To do so, it is necessary to know the frequency of the selected
      complications. OBJECTIVE: The aim of this study was to quantify complications
      during the first year after severe TBI. PARTICIPANTS: This study included
      patients 15 years or older who received subacute neurorehabilitation after severe
      TBI from 2011 to 2015 (N = 469). DESIGN: This is a register-based follow-up study
      using data from the Danish Head Trauma Database, a national clinical quality
      database aimed at monitoring and improving the quality of rehabilitation for
      patients with severe TBI. MAIN MEASURES: The following complications were
      assessed: urinary tract infection, pneumonia, pressure ulcers, joint
      contractures, and deep venous thrombosis. The prevalence of each complication was
      calculated at admission, discharge, and 1 year postinjury and for the period from
      admission and during subacute rehabilitation. In addition, the frequency of
      complications that certainly developed during subacute rehabilitation was
      calculated. Complications were compared between age-specific subgroups using
      multivariable binominal regression analyses. RESULTS: Urinary tract infections
      (53%) and pneumonia (32%) were the most common complications in the period from
      admission and during subacute rehabilitation. Pressure ulcers (18%), joint
      contractures (18%), and deep venous thrombosis (4%) were less frequent. At
      discharge and 1 year postinjury, the prevalence was less than 4% for all
      complications, except for joint contractures (16% and 13% at discharge and 1 year
      postinjury, respectively). CONCLUSION: The prevalence of complications was high.
      The findings are important for future quality improvement of the rehabilitation
      trajectory and for further studies that explore the high frequency of
      complications.

PMID- 29652736
TI  - Recommendations and Extraction of Clinical Variables of Pediatric Multiple
      Sclerosis Using Common Data Elements.
AB  - PURPOSE: The purpose of this article was to demonstrate the feasibility of using
      common data elements (CDEs) to search for information on the pediatric patient
      with multiple sclerosis (MS) and provide recommendations for future quality
      improvement and research in the use of CDEs for pediatric MS symptom management
      strategies Methods: The St. Louis Children's Hospital (SLCH), Washington
      University (WU) pediatrics data network was evaluated for use of CDEs identified
      from a database to identify variables in pediatric MS, including the key clinical
      features from the disease course of MS. The algorithms used were based on
      International Classification of Diseases, Ninth/Tenth Revision, codes and text
      keywords to identify pediatric patients with MS from a de-identified database.
      Data from a coordinating center of SLCH/WU pediatrics data network, which houses
      inpatient and outpatient records consisting of patients (N = 498 000), were
      identified, and detailed information regarding the clinical course of MS were
      located from the text of the medical records, including medications, presence of
      oligoclonal bands, year of diagnosis, and diagnosis code. RESULTS: There were 466
      pediatric patients with MS, with a few also having the comorbid diagnosis of
      anxiety and depression. CONCLUSIONS: St. Louis Children's Hospital/WU pediatrics
      data network is one of the largest databases in the United States of detailed
      data, with the ability to query and validate clinical data for research on MS.
      Nurses and other healthcare professionals working with pediatric MS patients will
      benefit from having common disease identifiers for quality improvement, research,
      and practice. The increased knowledge of big data from SLCH/WU pediatrics data
      network has the potential to provide information for intervention and decision
      making that can be personalized to the pediatric MS patient.

PMID- 29652737
TI  - Menopausal urogenital changes: welcome expansion of management options over the
      past 25 years.

PMID- 29652739
TI  - Commentary: Roger Baxter.

PMID- 29652738
TI  - 36th ESPID Annual Meeting in Malmo, Sweden May 28th - June 2nd 2018.

PMID- 29652740
TI  - Pneumococcal Immune Response in Infants Whose Mothers Received Tetanus,
      Diphtheria and Acellular Pertussis Vaccination During Pregnancy: ERRATUM.

PMID- 29652741
TI  - Vaccination in Pregnancy-Recent Developments: ERRATUM.

PMID- 29652742
TI  - Use of Linezolid in a Child With Tuberculous Meningitis.

PMID- 29652743
TI  - Expanding the Spectrum of Post-malaria Neurologic Syndrome in the Pediatric
      Population.

PMID- 29652744
TI  - Clinical pearls part 3: anaesthetic management of abnormally invasive
      placentation.
AB  - PURPOSE OF REVIEW: Abnormal placentation is a clinical condition seen
      increasingly in the pregnant population. It is associated with significant
      morbidity and mortality, which may be mitigated through robust multidisciplinary
      care for these patients. The role of maternal critical care for these patients
      has largely been ignored in the literature. RECENT FINDINGS: Advances in
      pharmacological management of bleeding with recent publications of large
      multicentre trials in addition to new technologies in the management of massive
      obstetric haemorrhage (MOH) have revolutionized the management of abnormal
      placentation. These include the use of tranexamic acid, interventional radiology,
      cell saver technology, and point-of-care coagulation tests. The role of maternal
      critical care for the optimization of postoperative complications and
      physiological derangements has not been considered widely in the literature. This
      article summarizes the current evidence for interventions and suggests a protocol
      for the management of these high-risk patients. SUMMARY: A robust protocol
      outlining the key elements of the management of placenta accreta, including
      optimizing postoperative care, should be in place to promote desired outcomes.

PMID- 29652745
TI  - Severe perineal lacerations after vaginal delivery: are they an
      anesthesiologist's problem?
AB  - PURPOSE OF REVIEW: Perineal tears or lacerations are common occurrences after
      vaginal delivery. Understanding the degree of severity of these tears and the
      immediate and long-term complications of severe perineal lacerations can assist
      anesthesiologists with the management of these patients in the immediate
      postpartum period. RECENT FINDINGS: Severe perineal lacerations have a high
      degree of association with postpartum depression. The presence of neuraxial labor
      analgesia decreases the odds of severe perineal lacerations. SUMMARY: Neuraxial
      labor analgesia does not directly predispose parturients to the development of
      perineal lacerations, and may even be protective against these injuries.

PMID- 29652746
TI  - Fluorine-18-fluorodeoxyglucose PET/CT in hematopoietic stem cell transplant
      patients with fusariosis: initial findings of a case series review.
AB  - BACKGROUND: Fusariosis is an opportunistic fungal infection that affects mostly
      leukemic and hematopoietic stem cell transplant patients. Locally invasive and
      disseminated infection may occur. Treatment is challenging, and besides
      evaluation of immune status, one also needs to take into account organ
      involvement to predict the duration and prognosis. OBJECTIVE: The aim of this
      study was to present the findings and clinical follow-up from a series of cases
      of Fusarium spp. infections in patients subjected to hematopoietic stem cell
      transplant evaluated with one or more fluorine-18-fluorodeoxyglucose (18F-FDG)
      PET/CT scans, according to the source of clinical culture sample (blood or wound
      secretion). RESULTS: Ten patients were included. In this series, 18F-FDG PET/CT
      was able to detect osteomyelitis in three patients. CONCLUSION: Although having a
      small number of patients and lack of standard approach, 18F-FDG PET/CT seemed
      useful to discriminate uncomplicated cases of primary bloodstream infections and
      detect occult foci of metastatic infection in patients with positive cutaneous
      lesions cultures.

PMID- 29652747
TI  - The incremental clinical value of cardiac hybrid SPECT/CTA imaging in coronary
      artery disease.
AB  - Coronary artery disease (CAD) is a major cause of death worldwide. It is
      significantly important to assess the coronary lesion and its pathophysiological
      relevance comprehensively. Coronary computed tomography angiography (CTA) or
      myocardial perfusion imaging alone suffers from some limitations in the
      evaluation of CAD. Through the integration and spatial colocalization of
      complementary morphological and functional information, the results of published
      hybrid single-photon emission computed tomography (SPECT)/CTA studies in patients
      with CAD are promising for detecting functionally relevant coronary artery lesion
      and evaluating the relationship between diseased coronary artery, coronary artery
      anomaly, myocardial bridging, or coronary calcification and myocardial ischemia.
      Compared with other diagnostic procedures, such as CTA, myocardial perfusion
      imaging alone, and side-by-side SPECT-CTA analysis, SPECT/CTA imaging has
      incremental value in the evaluation of CAD. Hybrid SPECT/CTA imaging can provide
      the physicians with more clinical evidence that helps with the treatment strategy
      decision-making process, thus acting as a gatekeeper to reduce unnecessary
      invasive examinations and revascularization procedures. In addition, follow-up
      SPECT/CTA fusion imaging plays a role in predicting prognosis by displaying
      clearly the relationship between postoperative vessel and myocardial blood
      supply. However, several limitations should be considered, including the
      increased radiation exposure, the limited number of patients, and the lack of a
      uniform gold standard. More data are needed to better specify the role of hybrid
      SPECT/CTA imaging in the management of CAD.

PMID- 29652748
TI  - The scintigraphic, biodistribution and histopathological evaluation of the effect
      of experimental 131I administration on the gastrointestinal system and the
      demonstration of the Na+/I- symporter by immunohistochemistry in rats.
AB  - OBJECTIVE: The aim of this study was to investigate histopathological changes and
      biodistribution of iodine-131 (I) in the gastrointestinal system (GIS) and also
      Na/I Symporter (NIS) presence by immunohistochemically in the experimental
      treatment of rats with radioactive iodine (RAI). MATERIALS AND METHODS: Rats were
      divided into experimental and control groups as random early group 2 (24 h),
      intermediate group 3 (3 weeks), and late period group 4 (3 months). Experimental
      groups were administered 100 MBq (~3 mCi, 12 mCi/kg) by orogastric route with
      orogastric tube. Scintigraphic iodine screening images were obtained 24 h, 3
      weeks, and 3 months after RAI, and GIS tissues were removed, and
      immunohistochemical methods were used to demonstrate NIS with RAI biodistribution
      and histopathology. RESULTS: According to the results of scintigraphy, the most
      prominent activity involvement was observed in the thyroid gland at group 2, and
      significant activity was observed in the stomach. In the group 3 and group 4
      images, owing to the physiological and biological half-life of the iodine and low
      resolution of the gamma camera, no secondary focal activation was observed. The
      highest RAI biodistribution value in all groups was in the stomach, ileum and
      oesophagus. In the immunohistochemical examination of NIS, the highest staining
      sequence was observed in all groups respectively in the stomach, oesophagus,
      tongue, colon, saliva, duodenum, rectum, ileum and jejunum. The increase of NIS
      immunohistochemically stained more intensely was observed in the RAI-administered
      groups. CONCLUSION: The amount of NIS is important for the absorption of RAI
      after administration.

PMID- 29652749
TI  - Sera From Children After Cardiopulmonary Bypass Reduces Permeability of Capillary
      Endothelial Cell Barriers.
AB  - OBJECTIVES: Children undergoing cardiopulmonary bypass develop clinically
      impactful capillary leak of unclear etiology. A widely held hypothesis that
      exposure of circulating cells to the cardiopulmonary bypass circuit induces the
      release of inflammatory mediators that act to disrupt intercellular junctions of
      capillary endothelial cells inducing paracellular capillary leak either directly
      or through new gene expression. DESIGN: Cohort study. SETTING: Tertiary pediatric
      hospital. PATIENTS: Twenty children undergoing surgery with cardiopulmonary
      bypass for congenital heart disease. Serum was collected before cardiopulmonary
      bypass, 2 hours after cardiopulmonary bypass, and 18 hours after cardiopulmonary
      bypass. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed the
      effects of 10% patient sera on the "function, structure, and gene expression" of
      cultured human dermal and pulmonary microvascular endothelial cells. Changes in
      barrier "function" were measured using transendothelial electrical resistance.
      Associations between changes in transendothelial electrical resistance and
      subject characteristics were analyzed using linear mixed effects model with area
      under the resistance curve as outcome. Changes in junctional "structure" were
      assessed by analyzing the organization of the endothelial cell junctional
      proteins claudin-5 and VE-cadherin using immunofluorescence microscopy. Changes
      in inflammatory "gene expression" were measured using real-time quantitative
      reverse transcription-polymerase chain reaction. All serum samples induced a
      transient, 120-minute increase in transendothelial electrical resistance followed
      by persistent loss of barrier function. Unexpectedly, sera collected
      postcardiopulmonary bypass-induced significantly less loss of barrier function in
      both dermal and pulmonary capillary endothelial cell compared with
      precardiopulmonary bypass sera. Consistent with the transendothelial electrical
      resistance results, claudin-5 and vascular endothelial-cadherin junctional
      staining showed less disruption in cultures treated with postcardiopulmonary
      bypass sera. Expression of genes commonly associated with inflammation was
      largely unaffected by patient sera. CONCLUSIONS: Contrary to the hypothesis, sera
      taken from children after cardiopulmonary bypass induces less capillary barrier
      disruption relative to sera taken from children before cardiopulmonary bypass,
      and none of the sera induced significant changes in expression of inflammatory
      genes.

PMID- 29652750
TI  - A Needs Assessment of Brain Death Education in Pediatric Critical Care Medicine
      Fellowships.
AB  - OBJECTIVES: To assess the current training in brain death examination provided
      during pediatric critical care medicine fellowship. DESIGN: Internet-based
      survey. SETTING: United States pediatric critical care medicine fellowship
      programs. SUBJECTS: Sixty-four pediatric critical care medicine fellowship
      program directors and 230 current pediatric critical care medicine fellows/recent
      graduates were invited to participate. INTERVENTIONS: Participants were asked
      demographic questions related to their fellowship programs, training currently
      provided at their fellowship programs, previous experience with brain death
      examinations (fellows/graduates), and perceptions regarding the adequacy of
      current training. MEASUREMENTS AND MAIN RESULTS: Twenty-nine program directors
      (45%) and 91 current fellows/graduates (40%) responded. Third-year fellows
      reported having performed a median of five examinations (interquartile range, 3
      6). On a five-point Likert scale, 93% of program directors responded they "agree"
      or "strongly agree" that their fellows receive enough instruction on performing
      brain death examinations compared with 67% of fellows and graduates (p = 0.007).
      The responses were similar when asked about opportunity to practice brain death
      examinations (90% vs 54%; p < 0.001). In a regression tree analysis, number of
      brain death examinations performed was the strongest predictor of trainee
      satisfaction. Both fellows and program directors preferred bedside demonstration
      or simulation as educational modalities to add to the fellowship curriculum.
      CONCLUSIONS: Pediatric critical care medicine fellows overall perform relatively
      few brain death examinations during their training. Pediatric critical care
      medicine fellows and program directors disagree in their perceptions of the
      current training in brain death examination, with fellows perceiving a need for
      increased training. Both program directors and fellows prefer additional training
      using bedside demonstration or simulation. Since clinical exposure to brain death
      examinations is variable, adding simulated brain death examinations to the
      pediatric critical care medicine fellowship curriculum could help standardize the
      experience.

PMID- 29652751
TI  - Igniting Innovation in Healthcare: A Novel Collaborative Multidisciplinary
      Approach in a PICU.
AB  - Generating innovation in the healthcare setting faces a number of challenges when
      compared with industry counterparts. More than ever, innovation occupies a
      critical element for healthcare organizations aspiring toward clinical, research
      and strategic excellence, although it may not exist as a priority due to a number
      of barriers. There are several strategies in other industries from which
      healthcare organizations can borrow, such as using nontraditional methods of
      problem solving, group ideation, and cross-pollination. As a high-intensity
      environment facing diverse challenges and conditions, the PICU is primed for
      building and generating innovation, which can be facilitated by implementing many
      of these strategies. This article describes an innovation program created to
      exercise a multidisciplinary approach for generating novel solutions in our PICU.
      Using nontraditional methods and ideation, this program has generated innovative
      solutions in an otherwise traditional setting, revealing new opportunities for
      growth, value generation, and collaboration between healthcare and the community.

PMID- 29652752
TI  - Practice Change From Intermittent Medication Boluses to Bolusing From a
      Continuous Infusion in Pediatric Critical Care: A Quality Improvement Project.
AB  - OBJECTIVES: To determine whether implementing a guideline to bolus medications
      from continuous infusions in PICUs affects nursing satisfaction, patient safety,
      central line entries, medication utilization, or cost. DESIGN: This is a pre- and
      postimplementation quality improvement study. SETTING: An 11-bed ICU and 14-bed
      cardiac ICU in a university-affiliated children's hospital. PATIENTS: Patients
      less than 18 years old admitted to the PICU or pediatric cardiac ICU receiving a
      continuous infusion of dexmedetomidine, midazolam, fentanyl, morphine,
      vecuronium, or cisatracurium from May 2015 to May 2016, excluding November 2015
      (washout period), were eligible for inclusion. INTERVENTIONS: Change in practice
      from administering bolus doses from an automated dispensing machine to
      administering bolus medications from continuous infusion in PICUs. MEASUREMENTS
      AND MAIN RESULTS: Timing studies were conducted pre- and post implementation in
      29 and 26 occurrences, respectively. The median time from the decision to give a
      bolus until it began infusing decreased by 169 seconds (p < 0.01). Nursing
      satisfaction increased from 19.3% pre- to 100% post implementation. Safety was
      assessed via barcode scanning compliance, which decreased by 1.4% for patients
      and 1% for medications, and smart pump limit overrides. The percentage of
      infusion pump bolus overrides increased as expected, with the majority (99%) of
      these exceeding soft maximum limits by less than two-fold. Central line entries
      were unaffected post implementation. To assess medication utilization, a total of
      50 patients in each intervention group were selected for retrospective chart
      review. Daily fentanyl boluses increased from one to three (p = 0.021). However,
      midazolam infusion dose and fentanyl infusion duration decreased (p = 0.026 and p
      = 0.005, respectively). Medication utilization was otherwise unchanged post
      implementation (p > 0.05). Annualized cost avoidance was $124,160. CONCLUSIONS:
      Implementation of bolus medications from continuous infusion in PICUs
      significantly decreased time to begin a bolus dose and increased nursing
      satisfaction. The practice change also improved medication utilization without
      negatively impacting patient safety.

PMID- 29652753
TI  - Hybrid Extracorporeal Therapies as a Bridge to Pediatric Liver Transplantation.
AB  - OBJECTIVES: Standard intensive care treatment is inadequate to keep children with
      liver failure alive without catastrophic complications to ensure successful
      transplant, as accumulation of endogenous protein-bound toxins often lead to
      hepatic encephalopathy, hepatorenal syndrome, cardiovascular instability, and
      multiple organ failure. Given paucity of proven treatment modalities for liver
      failure, blood purification using different extracorporeal treatments as a bridge
      to transplantation is used, but studies evaluating the safety and efficacy of
      combination of these therapies, especially in pediatric liver failure, are
      lacking. We describe our experience at a major tertiary children's hospital,
      where a unique hybrid extracorporeal treatment protocol has been instituted and
      followed for acute liver failure or acute-on-chronic liver failure as a bridge to
      transplantation. This protocol combines high-flux continuous renal replacement
      therapy for hyperammonemia, therapeutic plasma exchange for coagulopathy, and
      albumin-assisted dialysis (molecular adsorbent recirculating system) for hepatic
      encephalopathy. DESIGN: Retrospective observational study. SETTING: Freestanding
      tertiary children's hospital and liver transplant referral center. PATIENTS: All
      patients with acute liver failure/acute-on-chronic liver failure receiving hybrid
      extracorporeal therapy over 24 months. INTERVENTION: Hybdrid extracorporeal
      therapy. MEASUREMENTS AND MAIN RESULTS: Fifteen children (age 3 yr [0.7-9 yr];
      73% male) with acute liver failure/acute-on-chronic liver failure who were either
      listed or actively considered for listing and met our protocol criteria were
      treated with hybrid extracorporeal therapy; 93% were ventilated, and 80% were on
      vasoactive support. Of these, two patients recovered spontaneously, four died
      prior to transplant, and nine were successfully transplanted; 90-day survival
      post orthotopic liver transplant was 100%. Overall survival to hospital discharge
      was 73%. CONCLUSIONS: Hybrid extracorporeal therapies can be effectively
      implemented in pediatric liver failure as a bridge to transplantation. Overall
      complexity and heavy resource utilization need to be carefully considered in
      instituting these therapies in suitable candidates.

PMID- 29652754
TI  - Pattern of Antibiotic Prescription for Oral Implant Treatment Among Dentists in
      Saudi Arabia.
AB  - OBJECTIVE: To investigate antibiotic prophylaxis prescription behavior among
      dentists practicing dental implant surgery in Saudi Arabia. MATERIALS AND
      METHODS: An observational questionnaire study was conducted in the period between
      October 2016 and December 2016. A link to an online previously validated
      questionnaire was sent to a convenience sample of dentists practicing dental
      implant placement in the different areas of Saudi Arabia. Absolute frequencies
      were used to describe the data. RESULTS: One hundred nine completed
      questionnaires were received. A total of 59.63% (n = 65) of the respondents
      routinely prescribed prophylactic antibiotics when performing implant surgery.
      There was a wide variation in the preoperative and postoperative prescription
      regimens with the majority (67%) starting the antibiotic immediately
      postoperatively for 3 to 5 days, with no preoperative antibiotic use. Amoxicillin
      and clavulanic acid combination was the drug of choice for 50.3% of the
      respondents, whereas 26.6% prescribed amoxicillin as the drug of choice.
      CONCLUSION: Although a small study with a low response rate, a wide variation in
      antibiotic prescribing patterns with respect to the drugs chosen, timing, and
      duration was found in implant surgery in Saudi Arabia. Dentists should be aware
      of the risk of antibiotic overuse and start to share in the efforts that aim to
      reserve the antibiotics to combat life-threatening infections and to reduce
      development of bacterial resistance to the available antibiotics.

PMID- 29652755
TI  - Comprehensive Treatment and Rehabilitation of Patients With Osteosarcoma of the
      Mandible.
AB  - OBJECTIVE: The article studies state-of-the art physical therapeutic techniques
      as a high degree of relevance to minimize invalidation and improve quality of
      life for patients with dental osteosarcoma. MATERIALS AND METHODS: A randomized
      controlled clinical trial was conducted in 21 patients with osteogenic sarcoma of
      mandible (C41.1). There were 10 patients in the experimental group and 11
      patients in the control group. RESULTS: A comprehensive treatment and
      rehabilitation program for patients with osteosarcoma of mandible was developed.
      The first part of the program comprised 3 basic phases: preop chemotherapy,
      surgery, and postop rehabilitation. The surgical treatment further included
      resection of an affected part of the mandible and primary repair of the defect
      with jaw fragments and an autoimplant joined together with the help of
      positioning devices. The postop rehabilitation included postop chemotherapy and
      mesodiencephalic modulation (MDM). The second part of the program comprised preop
      examination, modeling, using stereolytic 3-dimensional models of the mandible,
      corrective surgeries, including implantation into the autoimplant-a fragment of
      patient's fibula, and building of a removable titanium alloy-based denture. MDM
      sessions were administered after each invasive intervention. CONCLUSIONS: Higher
      psychological and physical well-being was observed in the experimental group as
      compared with the control group (P < 0.01) in 2 weeks after the first surgery and
      2 months after scheduled corrective surgeries, which finished in denture
      installation.

PMID- 29652756
TI  - Radiological Evaluation of the Dimensions of Lower Molar Alveoli.
AB  - PURPOSE: The aim of the present radiological study was to analyze the alveolar
      bone morphology of the lower molars in physiological conditions. The main goal is
      to describe the bone anatomy of a hypothetically postextractive site in lower
      molar area. MATERIALS AND METHODS: Computed tomography scans of 100 patients were
      examined. Axial, paraxial, and Panorex sections were analyzed using a dedicated
      software. Precise reference points were encoded to make the bone measurements
      clear and repeatable. RESULTS: The total number of dental sites examined was 235.
      The mean available bone height was 13.32 +/- 3.23 mm in first molars and 11.76 +/
      2.82 mm in second molars. The inter-radicular septum was present in 86% out of
      cases in first molar sites and in 52% in second molar sites. The lingual cortex
      mean width, at the most coronal point, measured 1.41 +/- 0.52 mm in first molar
      alveoli and 1.67 +/- 0.66 mm in second molar alveoli. CONCLUSIONS: Proper
      clinical conditions, for scheduling a postextraction immediate implant placement
      surgery, involve the presence of 4 bone walls showing and sufficient height and
      width. The accurate knowledge of alveolus bone morphology of mandibular molars,
      prior extraction, could be an important guide to avoid potential failures due to
      nonideal anatomical features to fixture stabilization.

PMID- 29652757
TI  - Eliminating Survivor Bias in Two-stage Instrumental Variable Estimators.
AB  - Mendelian randomization studies commonly focus on elderly populations. This makes
      the instrumental variables analysis of such studies sensitive to survivor bias, a
      type of selection bias. A particular concern is that the instrumental variable
      conditions, even when valid for the source population, may be violated for the
      selective population of individuals who survive the onset of the study. This is
      potentially very damaging because Mendelian randomization studies are known to be
      sensitive to bias due to even minor violations of the instrumental variable
      conditions. Interestingly, the instrumental variable conditions continue to hold
      within certain risk sets of individuals who are still alive at a given age when
      the instrument and unmeasured confounders exert additive effects on the exposure,
      and moreover, the exposure and unmeasured confounders exert additive effects on
      the hazard of death. In this article, we will exploit this property to derive a
      two-stage instrumental variable estimator for the effect of exposure on
      mortality, which is insulated against the above described selection bias under
      these additivity assumptions.

PMID- 29652758
TI  - Is Inspiratory Muscle Weakness a Determinant of Endurance Exercise Tolerance
      During NIV-Supported Exercise in Patients With COPD?
AB  - PURPOSE: Previous research has reported that inspiratory muscle weakness is
      critical to decreased exercise tolerance and exercise tolerance improves with 10
      cmH2O pressure support ventilation in patients with chronic obstructive pulmonary
      disease (COPD). The purpose of this study was to evaluate the effects of
      proportional assist ventilation (PAV) and continuous positive airway pressure
      (CPAP) compared with sham on exercise tolerance in patients with and without
      inspiratory muscle weakness. METHODS: In a prospective design, 12 of 54 patients
      were eligible after clinical and comprehensive lung function evaluation,
      including maximum inspiratory pressure (MIP) measurement. Using baseline
      measures, participants were divided into 2 age-matched groups that differed in
      regard to MIP (Group 1, MIP <60 cmH2O, and Group 2, MIP >=60 cmH2O). Each
      participant performed 3 constant work rate tests with noninvasive support (PAV,
      CPAP, sham) in random order on different days at 80% of maximal incremental
      power. RESULTS: During the endurance tests, heart rate, peripheral oxygen
      saturation (SpO2), dyspnea perception scale, and exercise tolerance were
      measured. There were no significant differences between groups for heart rate,
      SpO2, dyspnea perception, or exercise tolerance during PAV, CPAP, or sham
      supported exercise (P > .05 for all). CONCLUSIONS: In this small representative
      group of patients with COPD, inspiratory muscle weakness was not a determining
      factor of performance during CPAP or PAV-supported aerobic exercise.

PMID- 29652759
TI  - Performance and Reproducibility of the Continuous Scale Physical Functional
      Performance 10 Test in Patients With Chronic Obstructive Pulmonary Disease: A
      CONTROLLED CROSS-SECTIONAL STUDY.
AB  - PURPOSE: To compare the performances of patients with chronic obstructive
      pulmonary disease (COPD) and healthy individuals on the Continuous Scale Physical
      Functional Performance 10 (PFP10) test and, second, to test the reproducibility
      of the PFP10 test in these participants. METHODS: In a prospective, cross
      sectional study, 28 patients with COPD (67 +/- 9 y, FEV1: 44.3 +/- 16.9% pred)
      and 12 healthy volunteers (healthy group) matched by age, body mass index, and
      sex were included. The participants performed 2 PFP10 tests 5 d apart. Main
      outcome measure was performance on the PFP10 test and included total score, score
      for specific domains, and total time to perform the PFP10 test. RESULTS: The
      functional performance of patients with COPD was worse than that of the healthy
      group on PFP10 total scores (43.9 +/- 12.6 vs 63.5 +/- 9.4, respectively; P <
      .001; effect size: 1.78) and time to complete the tasks (207.9 +/- 36.1 sec vs
      153.2 +/- 12.1 sec, respectively; P < .001, effect size: 2.27). In addition, the
      COPD group had significantly worse performance in the domains of upper-body
      strength, lower-body strength, balance and coordination, and endurance. The test
      was highly reproducible (ICC: 0.98; 95% CI, 0.96-0.99 for both groups), and the
      mean difference (upper and lower limits of agreement) of the total scores was -3
      (-9 to 3). CONCLUSIONS: The PFP10 test is a suitable and reproducible test for
      determining decreases in the functional performance of patients with COPD
      compared with healthy individuals.

PMID- 29652760
TI  - Influence of Disease Severity and Exercise Limitation on Exercise Training
      Intensity and Load and Health Benefits From Pulmonary Rehabilitation in Patients
      With COPD: AN EXPLORATORY STUDY.
AB  - PURPOSE: Some patients with chronic obstructive pulmonary disease (COPD) fail to
      achieve health benefits with pulmonary rehabilitation (PR). Exercise intensity
      and load represent stimulus for adaptation but it is unclear whether
      inappropriate exercise intensity and/or load are affected by severity of COPD,
      which may affect health benefits. The purpose was to determine whether COPD
      severity and/or the severity of pulmonary limitation to exercise (PLE) impacted
      exercising intensity or load and whether resultant intensity/load affected health
      outcomes derived from PR. METHODS: Patients with COPD (n = 58, age = 67 +/- 7 y,
      forced expiratory volume in the first second of expiration [FEV1] % predicted =
      52 +/- 21%) were recruited upon referral to PR. Primary health outcomes evaluated
      were 6-min walk distance and St George's Respiratory Questionnaire. Patients were
      stratified for disease severity using Global Initiative for Obstructive Lung
      Disease (GOLD) staging and PLE severity by change in inspiratory capacity during
      exercise. Exercise intensity and load were calculated from daily exercise
      records. RESULTS: Participants achieved comparable training duration and load
      regardless of GOLD severity. Patients with more severe PLE achieved greater
      training duration (more severe: 546 +/- 143 min., less severe: 451 +/- 109 min.,
      P = .036), and relative training load (more severe: 2200.8 +/- 595.3 kcal, less
      severe: 1648.3 +/- 597.8 kcal, P = .007). Greater overall training load was
      associated with greater improvements in 6-min walk distance (r = 0.24, P = .035).
      No significant relationships were observed between PLE, GOLD severity, training
      parameters, and St George's Respiratory Questionnaire response. CONCLUSIONS:
      Improvements in exercise tolerance can be explained by achieving greater training
      loads, demonstrating the importance of appropriate training load to maximize
      health outcomes in PR.

PMID- 29652761
TI  - Effect of Inspiratory Muscle Training in the Management of Patients With Asthma:
      A RANDOMIZED CONTROLLED TRIAL.
AB  - PURPOSE: The aim of this study was to investigate the effects of inspiratory
      muscle training (IMT) on respiratory muscle strength, exercise capacity, dyspnea,
      fatigue, quality of life, and daily living activities of asthmatic patients.
      METHODS: Thirty-eight asthmatic patients, between 18 and 65 years of age, were
      enrolled in the study and randomly divided into 2 groups; IMT (n = 20) or control
      (n = 18). Participants in the IMT group performed 30 breaths using a patient
      specific threshold pressure device, twice daily for 6 wk at 50% maximal
      inspiratory pressure (MIP), in addition to "breathing training" during this
      period. Participants in the control group performed only the "breathing training"
      (sham or no threshold pressure device). Outcome measurements, performed before
      and after the intervention, included pulmonary function test, respiratory muscle
      strength, 6-min walk test, modified Medical Research Council dyspnea scale, St
      George's Respiratory Questionnaire, Fatigue Severity Scale, and London Chest
      Activity of Daily Living scale. RESULTS: Among the outcomes in the study, changes
      to key variables including MIP (P < .01); MIP, percent predicted (P < .01);
      maximal expiratory pressure (MEP), percent predicted (P < .01); 6-min walk test
      walking distance (P = .001); modified Medical Research Council scale (P =<.001);
      Fatigue Severity Scale (P = .03); St George's Respiratory Questionnaire symptoms
      (P = .03); London Chest Activity of Daily Living domestic (P = .03); and London
      Chest Activity of Daily Living leisure (P = .01) were significantly different in
      favor of IMT versus control. CONCLUSION: These findings suggest that IMT may be
      an effective modality to enhance respiratory muscle strength, exercise capacity,
      quality of life, daily living activities, reduced perception of dyspnea, and
      fatigue in asthmatic patients.

PMID- 29652763
TI  - Forearm-Based Turnover Muscle Flaps for Elbow Soft-Tissue Reconstruction: A
      Comparison of Regional Coverage Based on Distal Flap Perfusion.
AB  - BACKGROUND: Elbow wounds pose a reconstructive challenge. Prior studies have
      described the vascular anatomy of both the brachioradialis and flexor carpi
      ulnaris muscle flaps. The goal of this study was to describe the distal flap
      perfusion of the flexor carpi radialis, with a direct comparison of the
      brachioradialis, flexor carpi ulnaris, and flexor carpi radialis muscle flaps for
      coverage around the elbow. METHODS: Six fresh-frozen upper extremity specimens
      were dissected for brachioradialis, flexor carpi radialis, and flexor carpi
      ulnaris flaps. Vascular data from prior studies were combined with our anatomical
      measurements to determine the area of perfused coverage around the elbow for the
      brachioradialis and flexor carpi ulnaris. The flexor carpi radialis flap distal
      vascular perfusion was examined separately with transverse sections at 1-cm
      intervals after India ink injections to determine distal flap perfusion and elbow
      coverage. Perfusion data were plotted on x and y axes over the posterior elbow.
      RESULTS: The brachioradialis muscle covered an average of 56 percent of the x
      axis and 7.4 percent of the y axis. The flexor carpi ulnaris muscle covered an
      average of 90 percent of the elbow along the x axis and 23.3 percent of elbow
      along the y axis. The flexor carpi radialis covered an average of 34 percent of
      the x axis and 4.8 percent of the y axis. CONCLUSION: The flexor carpi ulnaris
      muscle provides the most versatile and robust coverage over the posterior elbow,
      followed by the brachioradialis muscle, which consistently provides coverage over
      the lateral epicondyle.

PMID- 29652762
TI  - Distribution and Performance of Cardiovascular Risk Scores in a Mixed Population
      of HIV-Infected and Community-Based HIV-Uninfected Individuals in Uganda.
AB  - BACKGROUND: The utility and validity of cardiovascular diseases (CVD) risk scores
      are not well studied in sub-Saharan Africa. We compared and correlated CVD risk
      scores with carotid intima media thickness (c-IMT) among HIV-infected and
      uninfected people in Uganda. METHODS: We first calculated CVD risk using the (1)
      Framingham laboratory-based score; (2) Framingham nonlaboratory score (FRS-BMI);
      (3) Reynolds risk score; (4) American College of Cardiology and American Heart
      Association score; and (5) the Data collection on Adverse Effects of Anti-HIV
      Drugs score. We then compared absolute risk scores and risk categories across
      each score using Pearson correlation and kappa statistics, respectively. Finally,
      we fit linear regression models to estimate the strength of association between
      each risk score and c-IMT. RESULTS: Of 205 participants, half were females and
      median age was 49 years [interquartile range (IQR) 46-53]. Median CD4 count was
      430 cells/mm (IQR 334-546), with median 7 years of antiretroviral therapy
      exposure (IQR 6.4-7.5). HIV-uninfected participants had a higher median systolic
      blood pressure (121 vs. 110 mm Hg), prevalent current smokers (18% vs. 4%, P =
      0.001), higher median CVD risk scores (P < 0.003), and greater c-IMT (0.68 vs.
      0.63, P = 0.003). Overall, FRS-BMI was highly correlated with other risk scores
      (all rho >0.80). In linear regression models, we found significant correlations
      between increasing CVD risk and higher c-IMT (P < 0.01 in all models).
      CONCLUSIONS: In this cross-sectional study from Uganda, the FRS-BMI correlated
      well with standard risk scores and c-IMT. HIV-uninfected individuals had higher
      risk scores than HIV-infected individuals, and the difference seemed to be driven
      by modifiable factors.

PMID- 29652764
TI  - Our Surgical Repair for Macrostomia with Two Novel Small Triangular Flaps: Long
      Term Follow-Up and Results.
AB  - : The surgical methods for repairing congenital macrostomia should be carefully
      selected from both functional and aesthetic points of view. The surgical
      correction of macrostomia results in normal orbicularis oris function and
      symmetry of the repaired lip. In this article, the authors report their novel
      technique and the results obtained, assessed retrospectively. Twelve primary
      cases of macrostomia underwent surgical repair between 1996 and 2013. The age at
      surgery ranged from 3 to 78 months. The authors' operative procedure uses two
      small triangular flaps with a superficial layer of orbicularis muscle to preserve
      the dynamic action of muscle fibers attached to the skin of the triangular flaps,
      with suturing across the orbicularis muscle bundles. The optimal length of a
      medial small triangular flap is 1.5 to 2.0 mm, and the length of a lateral flap
      is 5 to 8 mm. Evaluation was based on the degree of symmetry of the lips as a
      ratio of the affected side to the unaffected side, and the scar characteristics.
      The follow-up period in this retrospective study ranged from 3 to 21 years. The
      same method was applied to all 12 cases in the reconstruction of a natural
      appearance and dynamic function of the oral commissure, and the results over
      several years showed satisfactory outcomes. The authors' technique is very useful
      in the primary surgery for macrostomia, as the dynamic action of muscle fibers is
      preserved, if the muscle is not dissected from the skin in the cleft margin that
      includes the two medial small triangular flaps. CLINICAL QUESTION/LEVEL OF
      EVIDENCE: Therapeutic, V.

PMID- 29652765
TI  - Using the BODY-Q to Understand Impact of Weight Loss, Excess Skin, and the Need
      for Body Contouring following Bariatric Surgery.
AB  - BACKGROUND: A consequence of bariatric surgery is redundant skin for most
      patients. The authors measured health-related quality of life and appearance
      following bariatric surgery in relation to weight loss, excess skin, and need for
      body contouring. METHODS: The sample included Canadian participants from the BODY
      Q field-test study recruited between November of 2013 and July of 2014.
      Participants were invited to complete BODY-Q scales and questions to assess
      weight loss, amount of excess skin, and need for body contouring between June 7,
      2016, and November 29, 2016. RESULTS: Two hundred fourteen participants responded
      (75 percent response rate). Of the 210 who underwent bariatric surgery, most were
      left with excess skin [n = 196 (93 percent)] and needed body contouring [n = 168
      (80 percent)]. Higher percentage total weight loss correlated with more excess
      skin (r = 0.24, p = 0.001), the need for more body contouring procedures (r =
      0.29, p < 0.001), and (worse) scores on seven of 13 BODY-Q scales. Having
      redundant skin correlated with more physical symptoms (r = 0.31, p < 0.001), the
      need for more body contouring procedures (r = 0.62, p < 0.001), and lower scores
      on 12 BODY-Q scales. The need for more body contouring procedures correlated with
      more physical symptoms (r = 0.23, p = 0.001) and lower scores on 12 BODY-Q
      scales. CONCLUSIONS: Excess skin after bariatric surgery is a disabling problem.
      Additional research using the BODY-Q is needed to determine improvements that can
      be achieved following body contouring.

PMID- 29652766
TI  - Chronic Recurrent Multifocal Osteomyelitis of the Mandible: A Diagnostic
      Challenge.
AB  - : Chronic recurrent multifocal osteomyelitis is a rare autoinflammatory bone
      disorder of children and adolescents characterized by monofocal or multifocal
      inflammatory bone lesions that are culture-negative on biopsy, associated with
      periods of exacerbation and resolution that can last over several months to
      years. Although it is predominantly a disease of long bones and the spine,
      craniofacial involvement is not uncommon, affecting the mandible in up to one
      fifth of cases. Similarities with other causes of osteitis in clinical
      presentation and imaging, and the lack of specific symptoms or laboratory tests,
      make chronic recurrent multifocal osteomyelitis mainly a diagnosis of exclusion.
      An accurate diagnosis is required for appropriate treatment to induce remission.
      This article highlights the challenges faced by plastic and oral surgeons in
      diagnosing mandibular chronic recurrent multifocal osteomyelitis, and describes
      two pediatric patients affected with the disease. Both cases were initially
      confused with other entities, leading to unnecessary initial treatments and a
      delayed diagnosis. A review aimed at surgeons summarizes the major aspects of
      this condition so that it is considered as a differential diagnosis in young
      patients presenting with a facial bony mass. CLINICAL QUESTION/LEVEL OF EVIDENCE:
      Therapeutic, V.

PMID- 29652767
TI  - Surgeon Volume and the Outcomes of Dupuytren's Surgery: Results from a Dutch
      Multicenter Study.
AB  - BACKGROUND: For many major surgical procedures, the outcomes are better when
      performed by surgeons with higher procedure volumes. The purpose of this study
      was to examine the relations between surgeon procedure volume and the outcomes of
      Dupuytren's surgery. METHODS: The authors conducted an observational study from
      2011 to 2014 at six dedicated hand surgery practice sites in The Netherlands.
      Five hundred eighty-eight patients underwent surgery for Dupuytren's contracture
      performed by one of the 16 surgeons. The main exposure variable was annual
      surgeon volume. Outcome measures were the degree of residual contracture, full
      release rate, and any postoperative adverse event examined within 3 months of
      surgery. RESULTS: Mean annual surgeon volume was 51 among the 16 surgeons(range;
      4-86) procedures. The majority of patients had primary disease (79 percent) and
      underwent open fasciectomy (74 percent). Multivariable regression analyses showed
      that surgeon volume was linearly related to all three outcomes, and identified no
      optimal volume threshold. Performing 10 additional procedures annually was
      independently associated with nearly 0.8 degree less residual contracture (p =
      0.002), 9 percent higher odds of attaining a full release (p = 0.037), and 11
      percent lower odds of an adverse event (p < 0.001). Nonetheless, patient-related
      factors had larger impacts on all three clinical outcomes than surgeon volume.
      CONCLUSIONS: In this study of practicing hand surgeons, surgeon volume varied
      widely, and a higher volume was associated with less postoperative residual
      contracture, higher full release rates, and fewer adverse events. This implies
      that increasing surgeon's procedure volume provides an opportunity for improving
      the outcomes of Dupuytren's surgery. CLINICAL QUESTION/LEVEL OF EVIDENCE:
      Therapeutic, III.

PMID- 29652768
TI  - Effect of One-Stage versus Two-Stage Palatoplasty on Hypernasality and Fistula
      Formation in Children with Complete Unilateral Cleft Lip and Palate: A Randomized
      Controlled Trial.
AB  - BACKGROUND: Is one-stage or two-stage palatoplasty more effective for preventing
      fistula formation and hypernasality in patients with complete unilateral cleft
      lip and palate? METHODS: This parallel blocked randomized controlled trial
      included 100 patients with nonsyndromic complete unilateral cleft lip and palate
      with a repaired cleft lip, divided into two equal groups. Group A had one-stage
      palatoplasty patients at age 12 to 13 months while group B had two-stage
      palatoplasty patients with soft palatoplasty at age 12 to 13 months and hard
      palatoplasty at age 24 to 25 months. Presence of a fistula was tested clinically
      at 3 years and speech was tested using nasometry and perceptual analyses at 6
      years. Group C consisted of noncleft controls (n = 20, age 6 years) for speech
      using nasometry. Fistula rates, hypernasality ratings, and nasalance scores were
      compared between groups A and B. Nasometry recordings of groups A and B were
      compared with control group C. RESULTS: There was no difference in fistula rates
      between groups A and B (p = 0.409; 95 percent CI, 0.365 to 11.9). Mean nasalance
      scores of group A showed higher nasalance than group B (p = 0.006; 95 percent CI,
      1.16 to 6.53). Perceptual analysis showed no difference between groups A and B (p
      = 0.837 and p = 1.000). Group A showed higher mean nasalance than group C (p =
      0.837 and p = 1.000), whereas group B showed no difference (p = 0.088; 95 percent
      CI, -0.14 to 2.02). CONCLUSIONS: There was no difference in fistula rates between
      groups. Nasalance was slightly higher in patients in the one-stage palatoplasty
      group than two-stage palatoplasty group, but the difference was not clinically
      significant. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

PMID- 29652769
TI  - Schizophrenia and Criminal Responsibility: A Systematic Review.
AB  - The significant progress of psychiatry in the 20th century provided a
      sophisticated theoretical framework to analyze the complex relationships between
      crime and mental illness. Schizophrenia has been traditionally associated with
      severe cognitive and affective deficits that heavily influence empathy, judgment
      capacities, but also control of impulsiveness. Although there is an association
      between psychotic disorders and absence or decrease of legal responsibility,
      their relationship is also determined by sociodemographic, developmental, and
      clinical factors. These disorders are associated not only with abolished criminal
      responsibility but also with diminished responsibility. We conduct a systematic
      literature review to examine the relation between schizophrenia and criminal
      responsibility. We have found that this clinical entity is often associated with
      diminished or abolished criminal liability. We discuss these findings, focusing
      on the specific deficits found in patients with schizophrenia and examining how
      this problem affects their behavior and eventually their accountability for their
      crimes.

PMID- 29652770
TI  - Psychiatric Services and "the Homeless": Changing the Paradigm.
AB  - Given the changes in our society and worldwide massive migrations across borders,
      this article argues that we need to change the paradigm of how we think about
      "the homeless," that is, to rethink our approach to not only those who cannot
      afford housing, the "economically homeless," but especially important also the
      larger group-those with chronic, serious medical-psychiatric-addictive disorders,
      the "medically/mentally ill homeless." We must place a greater emphasis on
      providing mental health services along with housing, legal, general medical,
      employment, and other services. The first and most crucial step toward adequate
      care is to understand these individuals and their lives as well as how we react
      to them. Second, we must become more proactive in helping those who live on the
      streets to receive adequate and coordinated services. And finally, for those who
      are unable to live independently in the community, we need to reinvent long-term,
      structured, humane residential, and inpatient settings.

PMID- 29652771
TI  - Treat the Patient, Not the Rule Book...: The Art of Psychopharmacology!
AB  - Experienced clinicians are aware that the results from clinical drug trials do
      not always translate to office practice. This essay suggests that clinicians use
      their own diagnostic and interviewing skills when treating with medications
      rather than simply relying on published data or suggested treatment algorithms.

PMID- 29652772
TI  - Attitudes Toward Disclosing a Mental Health Problem and Reemployment: A
      Longitudinal Study.
AB  - Despite low unemployment rates, individuals with mental health problems often
      struggle to gain reemployment. Many face the decision whether to disclose their
      mental illness to employers. This study therefore examined the role of disclosure
      attitudes for reemployment over time. Clinical and job search variables as well
      as attitudes toward disclosing a mental health issue to an employer were assessed
      among 301 unemployed individuals with mental health problems. Predictors of
      reemployment at 6-month follow-up were assessed using multiple regression,
      adjusted for sociodemographic variables, unemployment length, and depressive
      symptoms. Greater reluctance to disclose mental health problems at baseline
      predicted reemployment after 6 months. Reemployment was also associated with male
      sex, better education, lower disability levels, and more job offers at baseline.
      Therefore, a cautious approach toward disclosing a mental health problem may
      facilitate short-term reemployment. It is unclear whether this is a successful
      long-term strategy in employment settings.

PMID- 29652773
TI  - A Lonely Search?: Risk for Depression When Spirituality Exceeds Religiosity.
AB  - This study clarified longitudinal relations of spirituality and religiosity with
      depression. Spirituality's potential emphasis on internal (e.g., intrapsychic
      search for meaning) versus religiosity's potential emphasis on external (e.g.,
      engagement in socially-sanctioned belief systems) processes may parallel
      depression-linked cognitive-behavioral phenomena (e.g., rumination and
      loneliness) conceptually. Thus, this study tested the hypothesis that greater
      spirituality than religiosity, separate from the overall level of spirituality
      and religiosity, predicts longitudinal increases in depression. A national sample
      of midlife adults completed diagnostic interviews and questionnaires of spiritual
      and religious intensity up to three times over 18 years. In time-lagged
      multilevel models, overall spirituality plus religiosity did not predict
      depression. However, in support of the hypothesis, greater spirituality than
      religiosity significantly predicted subsequent increases in depressive symptoms
      and risk for major depressive disorder (odds ratio = 1.34). If replicated, the
      relative balance of spirituality and religiosity may inform depression assessment
      and prevention efforts.

PMID- 29652774
TI  - Commentary on Everly et al. (2016).

PMID- 29652776
TI  - The Effects of Traumatic and Multiple Loss on Psychopathology, Disability, and
      Quality of Life in Iraqi Asylum Seekers in the Netherlands: Erratum.

PMID- 29652775
TI  - Response to Commentary on Everly et al. (2016).

PMID- 29652777
TI  - Meta-Analysis of the Association Between FAS Ligand and TRAIL Genetic
      Polymorphisms and Intervertebral Disc Degeneration Susceptibility in Chinese Han
      population.
AB  - STUDY DESIGN: Meta-analysis to collect all the relevant studies to further
      investigate whether or not the FAS ligand (FASL) and tumor necrosis factor
      related apoptosis-inducing ligand (TRAIL) genetic polymorphisms are associated
      with susceptibility to intervertebral disc degeneration (IDD) in Chinese Han
      population. OBJECTIVE: To investigate whether or not the FASL and TRAIL genetic
      polymorphisms are associated with susceptibility to IDD in Chinese Han
      population. SUMMARY OF BACKGROUND DATA: FASL and TRAIL are both apoptotic gene.
      Several studies have assessed the associations of FASL and TRAIL gene with risk
      of IDD in Chinese Han population, but the results are inconsistent. METHODS: We
      systematically searched the PubMed, EMBASE, Medline, Scopus, Web of Science, CBM,
      and the Cochrane Library databases. Eligible studies assessing the polymorphisms
      in the FASL and TRAIL gene and risk of IDD were incorporated. The pooled odds
      ratio (OR) with its 95% confidence intervals (95% CI) was used. RESULTS: Six
      studies with a total of 1766 IDD cases and 1533 controls were finally included in
      the meta-analysis. Meta-analysis of FASL-844C/T (rs763110) polymorphism was
      statistically associated with decreased IDD risk under all genetic models (allele
      model: OR = 0.68, 95% CI 0.59-0.80, P = 0.000; homozygote model: OR = 0.35, 95%
      CI 0.25-0.53, P = 0.000; dominant model: OR = 0.38, 95% CI 0.25-0.58, P = 0.000;
      recessive model: OR = 0.69, 95% CI 0.58-0.84, P = 0.000). There was a significant
      association between TRAIL-1595C/T (rs1131580) polymorphism with increased IDD
      risk under each genetic model (allele model: OR = 1.77, 95% CI 1.47-2.13, P =
      0.000; homozygote model: OR = 2.44, 95% CI 1.70-3.51, P = 0.000; dominant model:
      OR = 1.67, 95% CI 1.22-2.29, P = 0.002; recessive model: OR = 3.13, 95% CI 2.40
      4.08, P = 0.000). In addition, the association between TRAIL-1525G/A (rs1131568)
      polymorphism and the susceptibility of IDD was statistically significant under
      all genetic models. CONCLUSION: The present meta-analysis demonstrated that FASL
      and TRAIL polymorphisms were significantly associated with susceptibility to IDD
      in Chinese Han population. LEVEL OF EVIDENCE: 1.

PMID- 29652778
TI  - Does the Use of Electrotherapies Increase the Effectiveness of Neck Stabilization
      Exercises for Improving Pain, Disability, Mood, and Quality of Life in Chronic
      Neck Pain?: A Randomized, Controlled, Single-Blind Study.
AB  - STUDY DESIGN: This study was a prospective, randomized, controlled study.
      OBJECTIVE: The aim of this study was to determine whether transcutaneous
      electrical nerve stimulation (TENS) or interferential current (IFC) increase the
      effectiveness of neck stabilization exercises (NSEs) on pain, disability, mood
      and quality of life for chronic neck pain (CNP). SUMMARY OF BACKGROUND DATA: Neck
      pain is one of the three most frequently reported complaints of the
      musculoskeletal system. Electrotherapies, such as IFC and TENS, have been applied
      solo or combined with exercise for management of neck pain; however, the efficacy
      of these combinations is unclear. METHODS: A total of 81 patients with CNP were
      included in this study. Patients were randomly assigned into three groups
      regarding age and gender. First group had NSE, second group had TENS and NSE, and
      third group had IFC and NSE. Pain levels [visual analogue scale (VAS)], limits of
      cervical range of motion (ROM), quality of life (short form-36), mood (Beck
      depression inventory), levels of disability (Neck Pain and Disability Index), and
      the need for analgesics of all patients were evaluated before treatment, at 6th
      and 12th week follow-up. Physical therapy modalities were applied for 15 sessions
      in all groups. All participants had group exercise accompanied by a
      physiotherapist for 3 weeks and an additional 3 weeks of home exercise program.
      RESULTS: According to the intragroup assessment, the study achieved its purpose
      of pain reduction, ROM increase, improvement of disability, quality of life, mood
      and reduction in drug use in all three treatment groups (P < 0.05). However,
      clinical outcomes at 6th and 12 th week had no significant difference among the
      three groups (P > 0.05). CONCLUSION: TENS and IFC therapies are effective in the
      treatment of CNP patients. However, they have no additional benefit or
      superiority over NSE. LEVEL OF EVIDENCE: 2.

PMID- 29652779
TI  - Is the Current Management of Patients Presenting With Spinal Trauma to District
      General Hospitals Fit for Purpose?: Our Experience of Delivering a Spinal Service
      Using an Electronic Referral Platform in a Large District General Teaching
      Hospital Without Onsite Spinal Services.
AB  - STUDY DESIGN: A retrospective cross-sectional analysis. OBJECTIVE: The aim of
      this study was to describe the provision of a spinal service using an electronic
      platform to direct management from an external spinal unit, and to quantify the
      time taken to obtain definitive management plans while under prescribed spinal
      immobilization. SUMMARY OF BACKGROUND DATA: Most attending district general
      hospitals following spinal trauma will have stable injuries and normal neurology,
      with only a small proportion requiring urgent transfer to a specialist center.
      METHODS: A retrospective review of 104 patients admitted following vertebral
      trauma during a 12-month period. The British Orthopaedic Association Standards
      for Trauma consensus that "spinal immobilisation is not recommended for more than
      48 hours" was the standard of care measured against. RESULTS: One hundred
      patients occupied a total of 975 hospital inpatient bed days. One hundred and
      seventeen radiological investigations were requested after the point of external
      referral [47 computed tomography (CT)-scans, 37 magnetic resonance imaging (MRI)
      scans, and 33 weight-bearing radiographs]. The period between initial referral to
      the regional spinal service and then receiving a definitive final management plan
      had a median value of 72 hours and a range of 0 and 33 days. Patients will have
      been under some form of prescribed spinal immobilization until the definitive
      management plan was communicated. Thirty-four patients (34% of the overall
      cohort) had a definitive management plan in place within 48 hours. Eighty
      patients had vertebral injuries (73 stable, six unstable), three patients had
      prolapsed intervertebral disks, one had metastatic disease, and 17 did not have
      evidence of an acute injury following evaluation. CONCLUSION: Patients are being
      placed under prescribed immobilization for longer than is recommended. Delays in
      obtaining radiological imaging were an important factor, together with the time
      taken to receive a definitive management plan. Limitations in social care
      provision and delays in arranging this were additional barriers to hospital
      discharge following the final management plan. LEVEL OF EVIDENCE: 4.

PMID- 29652780
TI  - Implication of Biomarker Mutations for Predicting Survival in Patients With
      Metastatic Lung Cancer to the Spine.
AB  - STUDY DESIGN: A retrospective cohort study. OBJECTIVE: We performed a
      retrospective study of patients treated at our institution over the last 7 years
      to ascertain whether gene expression signatures in patients with advanced
      metastatic disease are associated with survival, when the disease has progressed
      to the spine. SUMMARY OF BACKGROUND DATA: Spinal metastases are a major cause of
      morbidity in patients with cancer. Molecular profiling strategies to characterize
      lung cancer have identified several genetic biomarkers that may lead to more
      effective prognostication. METHODS: We queried our institutional database for
      patients with metastatic lung cancer who underwent treatment for spinal
      metastases between 2011 and 2017. Genetic mutations in ALK, MET, ROS1, EGFR, and
      KRAS were chosen a priori for study based on availability by standard SNaPshot
      Lung Tumor Genotyping Analysis. Survival time was the duration between treatment
      for spinal metastases and death. Kaplan-Meier methods and the log-rank test were
      applied to characterize survival data. RESULTS: Twenty-six patients met criteria
      for inclusion. Median survival after surgery was 0.67 years. Median overall
      survival (OS) after diagnosis was 2.7 years. The presence of molecular
      abnormalities in patients with spinal metastases was significantly associated
      with increased OS (HR 0.38, 95% CI 0.12-1.22, P = 0.03). CONCLUSION: Molecular
      phenotyping may provide prognostic insight in patients undergoing surgery for
      spinal metastases. This is the first study to demonstrate an association between
      genetic mutational data and OS in this patient population. It also represents the
      largest published series of such patients (n = 26) for which genetic mutational
      data are reported. Future models estimating survival for patients with spinal
      metastases may be enhanced by incorporation of molecular criteria. LEVEL OF
      EVIDENCE: 4.

PMID- 29652781
TI  - Pelvic Incidence Is Associated With Sacral Curvature, Sacroiliac Joint
      Angulation, and Sacral Ala Width.
AB  - STUDY DESIGN: Cross-sectional anatomical study in dry cadaveric specimens.
      OBJECTIVE: This study evaluates how the sacroiliac (SI) joint angulation,
      midsagittal sacral curvature, and sacral ala width relate to pelvic incidence
      (PI). SUMMARY OF BACKGROUND DATA: Numerous spinopelvic pathologies have been
      linked with pelvic incidence; however, the manner in which sacral morphology fits
      into this association is largely unknown. METHODS: A total of 120 cadaveric sacra
      and corresponding innominate bones were obtained from an osteological collection.
      Pelvic incidence was measured in a previously validated method. To gauge ala
      width, calipers were used to measure the distance between the midpoint of the
      sacral endplate and the anterolateral aspect of the right and left ala. Sacral
      curvature was evaluated by measuring the difference of the direct distance and
      the curved bony distance from the sacral promontory to the inferior aspect of the
      fourth intervertebral foramen. Three separate angle measurements were made to
      quantify the angulation of the SI joint, which we divided into an upper and lower
      limb. Angle 1 approximated the relationship between the upper limb and the sacral
      endplate; angle 2 between the upper and lower limbs; angle 3 between the lower
      limb and a tangential line to the fourth sacral foramen. RESULTS: Average age at
      death for all specimens was 31.9 +/- 6.3 years with 63% representation of males
      and an equal distribution of Caucasian and African Americans. The mean PI of our
      study population was 45.1 +/- 12.6 degrees . Results from our regression showed
      statistically significant associations between our measured angles evaluating SI
      joint angulation (angles 1, 2, 3) and PI. Standardized beta for angle 1 was 
      0.421, angle 2 was 0.419, and angle 3 was -0.439 (all P < 0.001). Additionally,
      the average endplate-ala distance (beta = -0.254) and average difference between
      tape-caliper measurements, our measurement for sacral arc, (beta = 0.178) were
      significantly associated with PI (all P < 0.05). CONCLUSION: Our data supports
      the theory that increased PI is associated with a highly angulated and curved
      sacrum, with corresponding changes in the SI joint, and narrowed sacral alae.
      LEVEL OF EVIDENCE: N/A.

PMID- 29652782
TI  - Impaired Trunk Posture in Women With Fibromyalgia.
AB  - STUDY DESIGN: A cross-sectional study. OBJECTIVES: The main goal of the study was
      to analyze posture of Fibromyalgia syndrome (FMS) in women compared with healthy
      subjects to establish if posture assessment could be useful to characterize the
      syndrome. Secondarily, we explored the impact of sedentary behavior on trunk
      posture. SUMMARY OF BACKGROUND DATA: Pain has been associated with poor static
      postures, however there is little information on the effect of FMS, which is
      characterized by widespread pain, on trunk posture. METHODS: One hundred eighteen
      women with FMS and 110 healthy counterparts participated in this study, in which
      trunk posture was assessed. The thoracic kyphosis, forward head position, and
      shoulder position (basal and maximum protraction) were measured. Further, maximum
      shoulder protraction and the ability to maintain the cervical and thoracic angle
      were assessed. To compare the differences in posture depending on the grouping,
      an independent Student t test was conducted. To analyze the differences between
      groups in the ability to maintain the position over a period of time and the
      differences in posture depending on more or less active lifestyles, two
      multivariate analysis of variance were performed. RESULTS: The results showed a
      significantly larger thoracic kyphosis, baseline shoulder protraction and lower
      craniovertebral angle and maximum protraction in FMG compared with CG (P < 0.05).
      FMG subjects exhibited an impaired ability to maintain the cervical and thoracic
      angles, as this varied throughout the test, unlike those of their counterparts. A
      sedentary lifestyle did not affect trunk posture in the FMS participants.
      CONCLUSION: FMS female population present an altered trunk posture and an
      inability to maintain trunk position. Since this does not appear to be influenced
      by a more or less active lifestyle, specific treatment programs are needed to
      manage this clinical condition. LEVEL OF EVIDENCE: 2.

PMID- 29652783
TI  - Minimum Clinically Important Difference in SF-36 Scores for Use in Degenerative
      Cervical Myelopathy.
AB  - STUDY DESIGN: Post-hoc analysis of 606 patients enrolled in the AOSpine CSM-NA or
      CSM-I prospective, multicenter cohort studies. OBJECTIVE: The aim of this study
      was to determine the minimum clinically important difference (MCID) in SF-36v2
      Physical Component Summary (PCS) and Mental Component Summary (MCS) scores in
      patients undergoing surgery for degenerative cervical myelopathy (DCM). SUMMARY
      OF BACKGROUND DATA: There has been a shift toward focus on patient-reported
      outcomes (PROs) in spine surgery. However, the numerical scores of PROs lack
      immediate clinical meaning. The MCID adds a dimension of interpretability to PRO
      scales; by defining the smallest change, a patient would consider meaningful.
      METHODS: The MCID of the SF-36v2 PCS and MCS were determined by distribution- and
      anchor-based methods comparing preoperative to 12-month scores. Distribution
      based approaches included calculation of the half standard deviation and standard
      error of measurement (SEM). Change in Neck Disability Index (NDI) served as the
      anchor: "worse" (DeltaNDI>7.5); "unchanged" (7.5>=DeltaNDI>-7.5); "slightly
      improved" (-7.5>=DeltaNDI>-15); and "markedly improved" (DeltaNDI <=-15).
      Receiver operating characteristic (ROC) analysis was performed to determine the
      change score for the MCID with even sensitivity and specificity to distinguish
      patients who were "slightly improved" versus "unchanged" on the NDI. RESULTS: The
      MCID for the SF-36v2 PCS and MCS were 4.6 and 6.8 by half standard deviation and
      2.9 and 4.3 by SEM, respectively. By ROC analysis, the MCID was 3.9 for the SF
      36v2 PCS score and 3.2 for the SF-36v2 MCS score. Using a cutoff of 4 points, the
      SF-36v2 PCS had a sensitivity of 72.2% and specificity of 68.1%, and MCS 61.9%
      and 64.6%, respectively, in separating patients who were "markedly improved" or
      "slightly improved" from those who were "unchanged" or "worse." CONCLUSION: We
      found the MCID of the SF-36v2 PCS and MCS to be 4 points. This will facilitate
      use of the SF-36v2 as an outcome in future studies of DCM. LEVEL OF EVIDENCE: 3.

PMID- 29652784
TI  - A Prospective, Randomized, Multicenter Study Comparing Silicated Calcium
      Phosphate versus BMP-2 Synthetic Bone Graft in Posterolateral Instrumented Lumbar
      Fusion for Degenerative Spinal Disorders.
AB  - STUDY DESIGN: A prospective, Phase IV, multicenter, randomized study. OBJECTIVE:
      The aim of this study was to compare vertebral fusion success rates following
      posterolateral fusion [(PLF)/posterolateral intertransverse fusion (PITF)]
      surgery. The surgical procedure combined posterior lumbar interbody fusion (PLIF)
      and PLF with internal fixation over one or two levels using silicated calcium
      phosphate (SiCaP) or bone morphogenetic protein (BMP)-2 as graft material in
      patients with a degenerative disorder of the lumbar spine. SUMMARY OF BACKGROUND
      DATA: Few controlled trials have evaluated the bone graft materials available to
      surgeons treating patients with spinal disorders, including degenerative disc
      disease, spondylolisthesis, and disc herniation. METHODS: Following
      randomization, the surgical procedure consisting of PLIF and PLF with internal
      fixation over one or two levels was performed using SiCaP or BMP-2. No other
      osteoconductive/osteoinductive graft materials were permitted. Spinal fusion was
      assessed radiographically at <=24 months. Clinical outcomes (pain on visual
      analog scale, Oswestry Disability Index, SF-36) and adverse events (AEs) were
      monitored. RESULTS: One hundred three patients were enrolled. At 12 months,
      fusion was achieved in 25 of 35 (71.4%) of the SiCaP and 20 of 27 (74.1%) of the
      BMP-2 group, respectively (P = 1.000). At 24 months, the fusion rate was 78.6%
      and 84.8% for SiCaP and BMP-2, respectively (P = 0.5613). Clinical outcomes
      improved similarly in both groups over time. AEs were consistent with this
      surgical population. CONCLUSION: SiCaP was safe and well tolerated in patients
      with degenerative spinal disorders requiring PLF and provided fusion rates
      similar to BMP-2. LEVEL OF EVIDENCE: 2.

PMID- 29652785
TI  - Clinical Prediction Rule for Heterotopic Ossification of the Hip in Patients with
      Spinal Cord Injury.
AB  - STUDY DESIGN: A case-control study; clinical prediction rule. OBJECTIVE: The aim
      of this study was to construct and internally validate a clinical prediction rule
      to identify patients at high risk of developing heterotopic ossification (HO)
      after spinal cord injury (SCI). SUMMARY OF BACKGROUND DATA: HO after SCI can lead
      to loss of joint mobility, loss of function, peripheral nerve entrapment, and
      pressure sores. HO is usually diagnosed on the basis of clinical symptoms, as no
      laboratory tests are yet available to identify patients with early HO formation.
      Risk factors include a complete SCI; patient age; spasticity; urinary tract
      infection (UTI); pneumonia; pelvic trauma; cervical or thoracic injury; and
      pressure sores. METHODS: We analyzed a total of 558 patients with SCI, of whom
      221 developed HO of the hip. A parametric survival model was fitted to estimate
      the probability of developing HO of the hip within 3 months of a SCI. Hazard
      ratios (HRs) calculation, internal validation, calibration, and model reduction
      were performed over 200 bootstrapped resamples. A risk score for clinical used
      was developed. RESULTS: Risk factors contributing to the risk score were
      completeness of the injury, age, sex, UTI, spasticity, and pneumonia. The model
      demonstrated good discrimination (AUC = 0.72). According to the risk score
      quintiles, the risk of developing HO after SCI was 1.0 for persons with a score
      of 0 to 17 and increased 2.47-fold for persons with a score of 1 to 21, 4.75-fold
      for persons with a score of 22 to 27, 6.95-fold for persons with a score of 28 to
      31, and 9.23-fold for persons with a score of 32-35. CONCLUSION: The risk score
      demonstrated good discrimination in predicting the occurrence of HO within 3
      months of a SCI. Further development and validation of the model in other
      populations is warranted. LEVEL OF EVIDENCE: 3.

PMID- 29652787
TI  - What's New in Shock, May 2018?

PMID- 29652786
TI  - Long-Term Results of Surgery Compared With Nonoperative Treatment for Lumbar
      Degenerative Spondylolisthesis in the Spine Patient Outcomes Research Trial
      (SPORT).
AB  - STUDY DESIGN: Randomized trial with a concurrent observational cohort study.
      OBJECTIVE: To compare 8-year outcomes between surgery and nonoperative care and
      among different fusion techniques for symptomatic lumbar degenerative
      spondylolisthesis (DS). SUMMARY OF BACKGROUND DATA: Surgical treatment of DS has
      been shown to be more effective than nonoperative treatment out to 4 years. This
      study sought to further determine the long-term (8-year) outcomes. METHODS:
      Surgical candidates with DS from 13 centers with at least 12 weeks of symptoms
      and confirmatory imaging were offered enrollment in a randomized controlled trial
      (RCT) or observational cohort study (OBS). Treatment consisted of standard
      decompressive laminectomy (with or without fusion) versus standard nonoperative
      care. Primary outcome measures were the Short Form-36 (SF-36) bodily pain and
      physical function scores and the modified Oswestry Disability Index at 6 weeks, 3
      months, 6 months, and yearly up to 8 years. RESULTS: Data were obtained for 69%
      of the randomized cohort and 57% of the observational cohort at the 8-year follow
      up. Intent-to-treat analyses of the randomized group were limited by high levels
      of nonadherence to the randomized treatment. As-treated analyses in the
      randomized and observational groups showed significantly greater improvement in
      the surgery group on all primary outcome measures at all time points through 8
      years. Outcomes were similar among patients treated with uninstrumented
      posterolateral fusion, instrumented posterolateral fusion, and 360 degrees 
      fusion. CONCLUSION: For patients with symptomatic DS, patients who received
      surgery had significantly greater improvements in pain and function compared with
      nonoperative treatment through 8 years of follow-up. Fusion technique did not
      affect outcomes. LEVEL OF EVIDENCE: 1.

PMID- 29652788
TI  - A Novel LiDAR-Based Instrument for High-Throughput, 3D Measurement of
      Morphological Traits in Maize and Sorghum.
AB  - Recently, imaged-based approaches have developed rapidly for high-throughput
      plant phenotyping (HTPP). Imaging reduces a 3D plant into 2D images, which makes
      the retrieval of plant morphological traits challenging. We developed a novel
      LiDAR-based phenotyping instrument to generate 3D point clouds of single plants.
      The instrument combined a LiDAR scanner with a precision rotation stage on which
      an individual plant was placed. A LabVIEW program was developed to control the
      scanning and rotation motion, synchronize the measurements from both devices, and
      capture a 360&deg; view point cloud. A data processing pipeline was developed for
      noise removal, voxelization, triangulation, and plant leaf surface
      reconstruction. Once the leaf digital surfaces were reconstructed, plant
      morphological traits, including individual and total leaf area, leaf inclination
      angle, and leaf angular distribution, were derived. The system was tested with
      maize and sorghum plants. The results showed that leaf area measurements by the
      instrument were highly correlated with the reference methods (R2 > 0.91 for
      individual leaf area; R2 > 0.95 for total leaf area of each plant). Leaf angular
      distributions of the two species were also derived. This instrument could fill a
      critical technological gap for indoor HTPP of plant morphological traits in 3D.

PMID- 29652790
TI  - Silicon and Mechanisms of Plant Resistance to Insect Pests.
AB  - This paper reviews the most recent progress in exploring silicon-mediated
      resistance to herbivorous insects and the mechanisms involved. The aim is to
      determine whether any mechanism seems more common than the others as well as
      whether the mechanisms are more pronounced in silicon-accumulating than non
      silicon-accumulating species or in monocots than eudicots. Two types of
      mechanisms counter insect pest attacks: physical or mechanical barriers and
      biochemical/molecular mechanisms (in which Si can upregulate and prime plant
      defence pathways against insects). Although most studies have examined high Si
      accumulators, both accumulators and non-accumulators of silicon as well as
      monocots and eudicots display similar Si defence mechanisms against insects.

PMID- 29652789
TI  - Terpenoids from the Soft Coral Sinularia sp. Collected in Yongxing Island.
AB  - Three new sesquiterpenoids (sinuketal (1), sinulins A and B (2 and 3)) and two
      new cembranoids (sinulins C and D (4 and 5)), as well as eight known
      sesquiterpenoids (6&ndash;13) and eight known cembranoids (14&ndash;21), were
      isolated from the Xisha soft coral Sinularia sp. Their structures were elucidated
      by extensive spectroscopic analysis. Compound 1 possesses an unprecedented
      isopropyl-branched bicyclo [6.3.0] undecane carbon skeleton with unique
      endoperoxide moiety, and a plausible biosynthetic pathway of it was postulated.
      According to the reported biological properties of endoperoxide, the
      antimalarial, cytotoxic, antiviral, and target inhibitory activities of 1 were
      tested. Compound 1 showed mild in vitro antimalarial activity against Plasmodium
      falciparum 3D7, weak cytotoxic activities toward Jurkat, MDA-MB-231, and U2OS
      cell lines, inhibitory effects against influenza A viruses H1N1 and PR8, as well
      as mild target inhibitory activity against acetylcholinesterase. The other
      compounds were evaluated for cytotoxicities against HeLa, HCT-116, and A549 tumor
      cell lines and target inhibitory activities against protein tyrosine phosphatase
      1B (PTP1B). Compound 20 exhibited cytotoxicities against HeLa and HCT-116, and
      compounds 5, 11, and 15 showed mild target inhibitory activities against PTP1B.

PMID- 29652791
TI  - An Efficient ABC_DE_Based Hybrid Algorithm for Protein-Ligand Docking.
AB  - Protein&ndash;ligand docking is a process of searching for the optimal binding
      conformation between the receptor and the ligand. Automated docking plays an
      important role in drug design, and an efficient search algorithm is needed to
      tackle the docking problem. To tackle the protein&ndash;ligand docking problem
      more efficiently, An ABC_DE_based hybrid algorithm (ADHDOCK), integrating
      artificial bee colony (ABC) algorithm and differential evolution (DE) algorithm,
      is proposed in the article. ADHDOCK applies an adaptive population partition
      (APP) mechanism to reasonably allocate the computational resources of the
      population in each iteration process, which helps the novel method make better
      use of the advantages of ABC and DE. The experiment tested fifty
      protein&ndash;ligand docking problems to compare the performance of ADHDOCK, ABC,
      DE, Lamarckian genetic algorithm (LGA), running history information guided
      genetic algorithm (HIGA), and swarm optimization for highly flexible
      protein&ndash;ligand docking (SODOCK). The results clearly exhibit the capability
      of ADHDOCK toward finding the lowest energy and the smallest root-mean-square
      deviation (RMSD) on most of the protein&ndash;ligand docking problems with
      respect to the other five algorithms.

PMID- 29652792
TI  - Influence of Blue Mussel (Mytilus edulis) Intake on Disease Activity in Female
      Patients with Rheumatoid Arthritis: The MIRA Randomized Cross-Over Dietary
      Intervention.
AB  - Rheumatoid Arthritis (RA) is a chronic inflammatory disease. This study evaluates
      the effect of blue mussel intake on disease activity and quality of life in women
      with RA. Thirty-nine women with established RA and a disease activity score 28
      (DAS28) >3.0 were recruited to a randomized 2 &times; 11-week cross-over dietary
      intervention. The participants continued with their medication and habitual diet
      and exchanged one cooked meal a day, five days a week, with a meal including 75 g
      blue mussels or 75 g meat. Diets were switched after an eight week washout
      period. Data regarding quality of life (SF-36), blood lipids, erythrocyte
      sediment rate (ESR), C-reactive protein (CRP) and tender and swollen joints were
      examined at the start and end of each dietary period. Thirty women completed one
      period, and twenty-three completed both. Intake of the blue mussel diet led to a
      significant reduction of DAS28-CRP (p = 0.048), but not DAS28. The number of
      EULAR (European League Against Rheumatism) criteria moderate and good responders
      were higher when consuming blue mussel diet (p = 0.036). Blood lipids did not
      change. To conclude, blue mussel intake reduced disease symptoms in women with RA
      and improved perceived health. The reported effects need to be confirmed by non
      patient reported outcomes, such as inflammation markers.

PMID- 29652793
TI  - Emerging Trends in Health Promotion for People with Disabilities.
AB  - The need among people with disabilities to improve their own health and
      prevent/manage secondary conditions requires a better balance between reactive
      and anticipatory care.

PMID- 29652794
TI  - The Voice of the Heart: Vowel-Like Sound in Pulmonary Artery Hypertension.
AB  - Increased blood pressure in the pulmonary artery is referred to as pulmonary
      hypertension and often is linked to loud pulmonic valve closures. For the purpose
      of this paper, it was hypothesized that pulmonary circulation vibrations will
      create sounds similar to sounds created by vocal cords during speech and that
      subjects with pulmonary artery hypertension (PAH) could have unique sound
      signatures across four auscultatory sites. Using a digital stethoscope, heart
      sounds were recorded at the cardiac apex, 2nd left intercostal space (2LICS), 2nd
      right intercostal space (2RICS), and 4th left intercostal space (4LICS)
      undergoing simultaneous cardiac catheterization. From the collected heart sounds,
      relative power of the frequency band, energy of the sinusoid formants, and
      entropy were extracted. PAH subjects were differentiated by applying the linear
      discriminant analysis with leave-one-out cross-validation. The entropy of the
      first sinusoid formant decreased significantly in subjects with a mean pulmonary
      artery pressure (mPAp) &ge; 25 mmHg versus subjects with a mPAp < 25 mmHg with a
      sensitivity of 84% and specificity of 88.57%, within a 10-s optimized window
      length for heart sounds recorded at the 2LICS. First sinusoid formant entropy
      reduction of heart sounds in PAH subjects suggests the existence of a vowel-like
      pattern. Pattern analysis revealed a unique sound signature, which could be used
      in non-invasive screening tools.

PMID- 29652795
TI  - Counteracting Akt Activation by HIV Protease Inhibitors in Monocytes/Macrophages.
AB  - Akt signaling plays a central role in many biological processes that are key
      players in human immunodeficiency virus 1 (HIV-1) pathogenesis. The persistence
      of latent reservoirs in successfully treated patients, mainly located in
      macrophages and latently infected resting CD4+ T cells, remains a major obstacle
      in HIV-1 eradication. We assessed the in vitro effects of an HIV protease
      inhibitor (PI) and a non-nucleoside reverse transcriptase inhibitor (NNRTI) on
      HIV-1 Nef-induced Akt activation in macrophages and on HIV-1 reactivation in U1
      monocytoid cells. Ex vivo, we investigated the impact of combination
      antiretroviral therapy (cART) on Akt activation, as measured by flow cytometry,
      and on the viral reservoir size, quantified by qPCR, in monocytes and autologous
      resting CD4+ T cells from HIV-infected individuals (Trial registration:
      NCT02858414). We found that, in myeloid cells, both Akt activation and HIV-1
      reactivation were inhibited by PI but not by NNRTI in vitro. Our results indicate
      that cART decreases Akt activation and reduces the size of the HIV reservoir in
      both monocytes and resting CD4+ T cells. Our study indicates that Akt activation
      could play a role in HIV reservoir formation, indicating that drugs which target
      Akt could be efficient for limiting its size in aviremic chronically infected
      patients.

PMID- 29652796
TI  - Expressing OsMPK4 Impairs Plant Growth but Enhances the Resistance of Rice to the
      Striped Stem Borer Chilo suppressalis.
AB  - Mitogen-activated protein kinases (MPKs) play a central role not only in plant
      growth and development, but also in plant responses to abiotic and biotic
      stresses, including pathogens. Yet, their role in herbivore-induced plant
      defenses and their underlying mechanisms remain largely unknown. Here, we cloned
      a rice MPK gene, OsMPK4, whose expression was induced by mechanical wounding,
      infestation of the striped stem borer (SSB) Chilo suppressalis, and treatment
      with jasmonic acid (JA), but not by treatment with salicylic acid (SA). The
      overexpression of OsMPK4 (oe-MPK4) enhanced constitutive and/or SSB-induced
      levels of JA, jasmonoyl-l-isoleucine (JA-Ile), ethylene (ET), and SA, as well as
      the activity of elicited trypsin proteinase inhibitors (TrypPIs), and reduced SSB
      performance. On the other hand, compared to wild-type plants, oe-MPK4 lines in
      the greenhouse showed growth retardation. These findings suggest that OsMPK4, by
      regulating JA-, ET-, and SA-mediated signaling pathways, functions as a positive
      regulator of rice resistance to the SSB and a negative regulator of rice growth.

PMID- 29652797
TI  - The Role of Gut Microbiota and Diet on Uremic Retention Solutes Production in the
      Context of Chronic Kidney Disease.
AB  - Uremic retention solutes (URS) are associated with cardiovascular complications
      and poor survival in chronic kidney disease. The better understanding of the
      origin of a certain number of these toxins enabled the development of new
      strategies to reduce their production. URS can be classified according to their
      origins (i.e., host, microbial, or exogenous). The discovery of the fundamental
      role that the intestinal microbiota plays in the production of many URS has
      reinstated nutrition at the heart of therapeutics to prevent the accumulation of
      URS and their deleterious effects. The intestinal microbiota is personalized and
      is strongly influenced by dietary habits, such as the quantity and the quality of
      dietary protein and fibers. Herein, this review out lines the role of intestinal
      microbiota on URS production and the recent discoveries on the effect of diet
      composition on the microbial balance in the host with a focus on the effect on
      URS production.

PMID- 29652798
TI  - The Double Face of Exosome-Carried MicroRNAs in Cancer Immunomodulation.
AB  - In recent years many articles have underlined the key role of nanovesicles, i.e.,
      exosomes, as information carriers among biological systems including cancer.
      Tumor-derived exosomes (TEXs) are key players in the dynamic crosstalk between
      cancer cells and the microenvironment while promote immune system control
      evasion. In fact, tumors are undoubtedly capable of silencing the immune response
      through multiple mechanisms, including the release of exosomes. TEXs have been
      shown to boost tumor growth and promote progression and metastatic spreading via
      suppression or stimulation of the immune response towards cancer cells. The
      advantage of immunotherapeutic treatment alone over combining immuno- and
      conventional therapy is currently debated. Understanding the role of tumor
      exosome-cargo is of crucial importance for our full comprehension of neoplastic
      immonosuppression and for the construction of novel therapies and vaccines based
      on (nano-) vesicles. Furthermore, to devise new anti-cancer approaches, diverse
      groups investigated the possibility of engineering TEXs by conditioning cancer
      cells&rsquo; own cargo. In this review, we summarize the state of art of TEX
      based immunomodulation with a particular focus on the molecular function of non
      coding family genes, microRNAs. Finally, we will report on recent efforts in the
      study of potential applications of engineered exosomes in cancer immunotherapy.

PMID- 29652799
TI  - Combination Kinase Inhibitor Treatment Suppresses Rift Valley Fever Virus
      Replication.
AB  - Viruses must parasitize host cell translational machinery in order to make
      proteins for viral progeny. In this study, we sought to use this signal
      transduction conduit against them by inhibiting multiple kinases that influence
      translation. Previous work indicated that several kinases involved in
      translation, including p70 S6K, p90RSK, ERK, and p38 MAPK, are phosphorylated
      following Rift Valley fever virus (RVFV) infection. Furthermore, inhibiting p70
      S6K through treatment with the FDA approved drug rapamycin prevents RVFV
      pathogenesis in a mouse model of infection. We hypothesized that inhibiting
      either p70 S6K, p90RSK, or p90RSK&rsquo;s upstream kinases, ERK and p38 MAPK,
      would decrease translation and subsequent viral replication. Treatment with the
      p70 S6K inhibitor PF-4708671 resulted in decreased phosphorylation of
      translational proteins and reduced RVFV titers. In contrast, treatment with the
      p90RSK inhibitor BI-D1870, p38MAPK inhibitor SB203580, or the ERK inhibitor
      PD0325901 alone had minimal influence on RVFV titers. The combination of PF
      4708671 and BI-D1870 treatment resulted in robust inhibition of RVFV replication.
      Likewise, a synergistic inhibition of RVFV replication was observed with p38MAPK
      inhibitor SB203580 or the ERK inhibitor PD0325901 combined with rapamycin
      treatment. These findings serve as a proof of concept regarding combination
      kinase inhibitor treatment for RVFV infection.

PMID- 29652800
TI  - Full Genome Sequencing Reveals New Southern African Territories Genotypes
      Bringing Us Closer to Understanding True Variability of Foot-and-Mouth Disease
      Virus in Africa.
AB  - Foot-and-mouth disease virus (FMDV) causes a highly contagious disease of cloven
      hooved animals that poses a constant burden on farmers in endemic regions and
      threatens the livestock industries in disease-free countries. Despite the
      increased number of publicly available whole genome sequences, FMDV data are
      biased by the opportunistic nature of sampling. Since whole genomic sequences of
      Southern African Territories (SAT) are particularly underrepresented, this study
      sequenced 34 isolates from eastern and southern Africa. Phylogenetic analyses
      revealed two novel genotypes (that comprised 8/34 of these SAT isolates) which
      contained unusual 5&prime; untranslated and non-structural encoding regions.
      While recombination has occurred between these sequences, phylogeny violation
      analyses indicated that the high degree of sequence diversity for the novel SAT
      genotypes has not solely arisen from recombination events. Based on estimates of
      the timing of ancestral divergence, these data are interpreted as being
      representative of un-sampled FMDV isolates that have been subjected to
      geographical isolation within Africa by the effects of the Great African
      Rinderpest Pandemic (1887&ndash;1897), which caused a mass die-out of FMDV
      susceptible hosts. These findings demonstrate that further sequencing of African
      FMDV isolates is likely to reveal more unusual genotypes and will allow for
      better understanding of natural variability and evolution of FMDV.

PMID- 29652801
TI  - The Crystal Structure of the R280K Mutant of Human p53 Explains the Loss of DNA
      Binding.
AB  - The p53 tumor suppressor is widely found to be mutated in human cancer. This
      protein is regarded as a molecular hub regulating different cell responses,
      namely cell death. Compelling data have demonstrated that the impairment of p53
      activity correlates with tumor development and maintenance. For these reasons,
      the reactivation of p53 function is regarded as a promising strategy to halt
      cancer. In the present work, the recombinant mutant p53R280K DNA binding domain
      (DBD) was produced for the first time, and its crystal structure was determined
      in the absence of DNA to a resolution of 2.0 A. The solved structure contains
      four molecules in the asymmetric unit, four zinc(II) ions, and 336 water
      molecules. The structure was compared with the wild-type p53 DBD structure,
      isolated and in complex with DNA. These comparisons contributed to a deeper
      understanding of the mutant p53R280K structure, as well as the loss of DNA
      binding related to halted transcriptional activity. The structural information
      derived may also contribute to the rational design of mutant p53 reactivating
      molecules with potential application in cancer treatment.

PMID- 29652802
TI  - TUNEL Assay and DAPI Staining Revealed Few Alterations of Cellular Morphology in
      Naturally and Artificially Aged Seeds of Cultivated Flax.
AB  - In a search for useful seed aging signals as biomarkers for seed viability
      prediction, we conducted an experiment using terminal deoxynucleotidyl
      transferase mediated dUTP nick end labeling (TUNEL) assay and 4&prime;,6
      diamidino-2-phenylindole (DAPI) staining to analyze morphological and molecular
      changes in naturally aged (NA) and artificially aged (AA) flax (Linum
      usitatissimum L.) seeds. A total of 2546 sections were performed from 112 seeds
      of 12 NA and AA seed samples with variable germination rates. Analyzing 1384
      micrographs generated from TUNEL assay and DAPI staining revealed few alterations
      of the cellular morphology of the NA and AA seeds. Also, the revealed DNA
      degradations in the aged flax seeds appeared to be associated with seed samples
      of low germination rates. These results suggest that oily flax seed aging may
      alter the cellular morphology differently than starchy wheat seed aging. The
      results also imply that the TUNEL assay and DAPI staining may not yield
      informative assessments on cellular alterations and DNA degradation after the
      aging of oily seeds.

PMID- 29652804
TI  - Cerebrospinal Fluid Concentrations of Biogenic Amines: Potential Biomarkers for
      Diagnosis of Bacterial and Viral Meningitis.
AB  - Catecholamine and serotonin are biogenic amines (BAs) that serve as
      neurotransmitters and play an important role in the regulation of cardinal
      functions that are mainly altered during central nervous system (CNS) infections.
      A total 92 samples of cerebrospinal fluid (CSF) were classified into 4 groups
      based on their etiology. In these samples, BAs/neurotransmitters i.e., dopamine
      (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5
      hydroxyindoleacetic acid (5HIAA) were detected and quantified by high performance
      liquid chromatography with electrochemical detection (HPLC-EC) to determine the
      neurophysiology of the CNS infections by bacteria (Listeria monocytogenes (Lm)
      and Neisseria meningitidis (Nm)) and herpes simplex virus (HSV). CSF
      concentration of DA, DOPAC, HVA, and 5HIAA were found significantly elevated in
      all test cohorts. Present study highlights that the analysis of BAs is pivotal
      for the early diagnosis of bacterial and viral meningitis. In addition,
      coinfections of varied etiology can also be diagnosed by their quantification.
      Thus, BAs can serve as potential biomarkers of these CNS infections.

PMID- 29652803
TI  - Hypoxia Supports Epicardial Cell Differentiation in Vascular Smooth Muscle Cells
      through the Activation of the TGFbeta Pathway.
AB  - : Epicardium-derived cells (EPDCs) are an important pool of multipotent
      cardiovascular progenitor cells. Through epithelial-to-mesenchymal-transition
      (EMT), EPDCs invade the subepicardium and myocardium and further differentiate
      into several cell types required for coronary vessel formation. We previously
      showed that epicardial hypoxia inducible factor (HIF) signaling mediates the
      invasion of vascular precursor cells critical for patterning the coronary
      vasculature. Here, we examine the regulatory role of hypoxia (1% oxygen) on EPDC
      differentiation into vascular smooth muscle cells (VSMCs). RESULTS: Hypoxia
      stimulates EMT and enhances expression of several VSMC markers in mouse
      epicardial cell cultures. This stimulation is specifically blocked by inhibiting
      transforming growth factor-beta (TGF&beta;) receptor I. Further analyses
      indicated that hypoxia increases the expression level of TGF&beta;-1 ligand and
      phosphorylation of TGF&beta; receptor II, suggesting an indispensable role of the
      TGF&beta; pathway in hypoxia-stimulated VSMC differentiation. We further
      demonstrate that the non-canonical RhoA/Rho kinase (ROCK) pathway acts as the
      main downstream effector of TGF&beta; to modulate hypoxia&rsquo;s effect on VSMC
      differentiation. CONCLUSION: Our results reveal a novel role of epicardial HIF in
      mediating coronary vasculogenesis by promoting their differentiation into VSMCs
      through noncanonical TGF&beta; signaling. These data elucidate that patterning of
      the coronary vasculature is influenced by epicardial hypoxic signals.

PMID- 29652805
TI  - Research on a Visual Electronic Nose System Based on Spatial Heterodyne
      Spectrometer.
AB  - Light absorption gas sensing technology has the characteristics of massive
      parallelism, cross-sensitivity and extensive responsiveness, which make it
      suitable for the sensing task of an electronic nose (e-nose). With the
      performance of hyperspectral resolution, spatial heterodyne spectrometer (SHS)
      can present absorption spectra of the gas in the form of a two dimensional (2D)
      interferogram which facilitates the analysis of gases with mature image
      processing techniques. Therefore, a visual e-nose system based on SHS was
      proposed. Firstly, a theoretical model of the visual e-nose system was
      constructed and its visual maps were obtained by an experiment. Then the local
      binary pattern (LBP) and Gray-Level Co-occurrence Matrix (GLCM) were used for
      feature extraction. Finally, classification algorithms based on distance
      similarity (Correlation coefficient (CC); Euclidean distance to centroids (EDC))
      were chosen to carry on pattern recognition analysis to verify the feasibility of
      the visual e-nose system.

PMID- 29652807
TI  - Microstructural Evolution and Mechanical Properties in Superlight Mg-Li Alloy
      Processed by High-Pressure Torsion.
AB  - Microstructural evolution and mechanical properties of LZ91 Mg-Li alloy processed
      by high-pressure torsion (HPT) at an ambient temperature were researched in this
      paper. The microstructure analysis demonstrated that significant grain refinement
      was achieved after HPT processing with an average grain size reducing from 30
      &mu;m (the as-received condition) to approximately 230 nm through 10 turns. X-ray
      diffraction analysis revealed LZ91 alloy was consisted of &alpha; phase
      (hexagonal close-packed structure, hcp) and &beta; phase (body-centered cubic
      structure, bcc) before and after HPT processing. The mean value of microhardness
      increased with the increasing number of HPT turns. This significantly increased
      hardness of specimens can be explained by Hall-Petch strengthening.
      Simultaneously, the distribution of microhardness along the specimens was
      different from other materials after HPT processing due to the different
      mechanical properties of two different phases. The mechanical properties of LZ91
      alloy processed by HPT were assessed by the micro-tensile testing at 298, 373,
      423, and 473 K. The results demonstrate that the ultra-fine grain LZ91 Mg-Li
      alloy exhibits excellent mechanical properties: tensile elongation is
      approximately 400% at 473 K with an initial strain rate of 1 &times; 10&minus;2
      s&minus;1.

PMID- 29652808
TI  - The Impact of an Integrated Program of Return-to-Field and Targeted Trap-Neuter
      Return on Feline Intake and Euthanasia at a Municipal Animal Shelter.
AB  - Available evidence indicates that overall levels of feline intake and euthanasia
      at U.S. shelters have significantly declined in recent decades. Nevertheless,
      millions of cats, many of them free-roaming, continue to be admitted to shelters
      each year. In some locations, as many as 70% of cats, perhaps up to one million
      or more per year nationally, are euthanized. New approaches, including return-to
      field (RTF) and targeted trap-neuter-return (TNR) appear to have transformative
      potential. The purpose of the present study was to examine changes in feline
      intake and euthanasia, as well as additional associated metrics, at a municipal
      animal shelter in Albuquerque, New Mexico, after institutionalized RTF and
      targeted TNR protocols, together referred to as a community cat program (CCP),
      were added to ongoing community-based TNR efforts and a pilot RTF initiative.
      Over the course of the CCP, which ran from April 2012 to March 2015, 11,746 cats
      were trapped, sterilized, vaccinated, and returned or adopted. Feline euthanasia
      at the Albuquerque Animal Welfare Department (AAWD) declined by 84.1% and feline
      intake dropped by 37.6% over three years; the live release rate (LRR) increased
      by 47.7% due primarily to these reductions in both intake and euthanasia. Modest
      increases in the percentage of cats returned to owner (RTO) and the adoption rate
      were also observed, although both metrics decreased on an absolute basis, while
      the number of calls to the city about dead cats declined.

PMID- 29652806
TI  - Excessive Extracellular ATP Desensitizes P2Y2 and P2X4 ATP Receptors Provoking
      Surfactant Impairment Ending in Ventilation-Induced Lung Injury.
AB  - Stretching the alveolar epithelial type I (AT I) cells controls the intercellular
      signaling for the exocytosis of surfactant by the AT II cells through the
      extracellular release of adenosine triphosphate (ATP) (purinergic signaling).
      Extracellular ATP is cleared by extracellular ATPases, maintaining its
      homeostasis and enabling the lung to adapt the exocytosis of surfactant to the
      demand. Vigorous deformation of the AT I cells by high mechanical power
      ventilation causes a massive release of extracellular ATP beyond the clearance
      capacity of the extracellular ATPases. When extracellular ATP reaches levels >100
      &mu;M, the ATP receptors of the AT II cells become desensitized and surfactant
      impairment is initiated. The resulting alteration in viscoelastic properties and
      in alveolar opening and collapse time-constants leads to alveolar collapse and
      the redistribution of inspired air from the alveoli to the alveolar ducts, which
      become pathologically dilated. The collapsed alveoli connected to these dilated
      alveolar ducts are subject to a massive strain, exacerbating the ATP release.
      After reaching concentrations >300 &mu;M extracellular ATP acts as a danger
      associated molecular pattern, causing capillary leakage, alveolar space edema,
      and further deactivation of surfactant by serum proteins. Decreasing the tidal
      volume to 6 mL/kg or less at this stage cannot prevent further lung injury.

PMID- 29652809
TI  - Characterization of Chlorella sorokiniana, UTEX 1230.
AB  - This paper characterizes the strain Chlorella sorokiniana UTEX 1230 within a
      laboratory setting using a 1 L bubble column. The findings show that productivity
      can be trebled under mixotrophic conditions (from 0.2
      g&middot;L&minus;1&middot;d&minus;1 to 0.66 g&middot;L&minus;1&middot;d&minus;1)
      with the addition of sodium acetate. The results also indicate that both the
      growth rate and final yield increase with the cultivation temperature, with most
      parameters showing an optimum in the range of 30&ndash;35 &deg;C. The maximum
      specific growth rate was found to be in the region of 0.12 h&minus;1 at a surface
      irradiance between 100&ndash;500 &micro;E&middot;m&minus;2&middot;s&minus;1. This
      high growth rate makes the strain particularly suited to the rapid production of
      biomass, suitable for either whole cell bioprocessing or bioremediation. However,
      the relatively low lipid productivity (9.2 mg&middot;L&minus;1&middot;d&minus;1)
      confirms previous findings which would indicate poor applicability for biodiesel
      production. The strain shows greater promise in wastewater treatment applications
      with removal rates of nitrogen and phosphorus in the region of 37 and 30
      mg&middot;L&minus;1&middot;d&minus;1 respectively. Furthermore, the findings show
      that a fed-batch strategy to inorganic nutrient loading can increase the final
      yield by around 50% compared to a conventional batch run. This is particularly
      interesting as fed-batch production techniques are rarely used within microalgal
      cultivation, so provide an interesting avenue for further investigation. Overall,
      the findings show that C. sorokiniana UTEX 1230 is a robust and fast-growing
      microalgal strain suitable both for the laboratory and scale-up.

PMID- 29652810
TI  - Edge-Based Efficient Search over Encrypted Data Mobile Cloud Storage.
AB  - Smart sensor-equipped mobile devices sense, collect, and process data generated
      by the edge network to achieve intelligent control, but such mobile devices
      usually have limited storage and computing resources. Mobile cloud storage
      provides a promising solution owing to its rich storage resources, great
      accessibility, and low cost. But it also brings a risk of information leakage.
      The encryption of sensitive data is the basic step to resist the risk. However,
      deploying a high complexity encryption and decryption algorithm on mobile devices
      will greatly increase the burden of terminal operation and the difficulty to
      implement the necessary privacy protection algorithm. In this paper, we propose
      ENSURE (EfficieNt and SecURE), an efficient and secure encrypted search
      architecture over mobile cloud storage. ENSURE is inspired by edge computing. It
      allows mobile devices to offload the computation intensive task onto the edge
      server to achieve a high efficiency. Besides, to protect data security, it
      reduces the information acquisition of untrusted cloud by hiding the relevance
      between query keyword and search results from the cloud. Experiments on a real
      data set show that ENSURE reduces the computation time by 15% to 49% and saves
      the energy consumption by 38% to 69% per query.

PMID- 29652811
TI  - Spatial Distribution of Stony Desertification and Key Influencing Factors on
      Different Sampling Scales in Small Karst Watersheds.
AB  - Karst areas are typical ecologically fragile areas, and stony desertification has
      become the most serious ecological and economic problems in these areas worldwide
      as well as a source of disasters and poverty. A reasonable sampling scale is of
      great importance for research on soil science in karst areas. In this paper, the
      spatial distribution of stony desertification characteristics and its influencing
      factors in karst areas are studied at different sampling scales using a grid
      sampling method based on geographic information system (GIS) technology and geo
      statistics. The rock exposure obtained through sampling over a 150 m &times; 150
      m grid in the Houzhai River Basin was utilized as the original data, and five
      grid scales (300 m &times; 300 m, 450 m &times; 450 m, 600 m &times; 600 m, 750 m
      &times; 750 m, and 900 m &times; 900 m) were used as the subsample sets. The
      results show that the rock exposure does not vary substantially from one sampling
      scale to another, while the average values of the five subsamples all fluctuate
      around the average value of the entire set. As the sampling scale increases, the
      maximum value and the average value of the rock exposure gradually decrease, and
      there is a gradual increase in the coefficient of variability. At the scale of
      150 m &times; 150 m, the areas of minor stony desertification, medium stony
      desertification, and major stony desertification in the Houzhai River Basin are
      7.81 km2, 4.50 km2, and 1.87 km2, respectively. The spatial variability of stony
      desertification at small scales is influenced by many factors, and the
      variability at medium scales is jointly influenced by gradient, rock content, and
      rock exposure. At large scales, the spatial variability of stony desertification
      is mainly influenced by soil thickness and rock content.

PMID- 29652812
TI  - Radical-Mediated Reactions of alpha-Bromo Aluminium Thioacetals, alpha
      Bromothioesters, and Xanthates for Thiolactone Synthesis.
AB  - Thiolactones have attracted considerable attention in recent years as bioactive
      natural products, lead compounds for drug discovery, molecular probes, and
      reagents for polymerisation. We have investigated radical-mediated C-C bond
      forming reactions as a strategy for thiolactone synthesis. Cyclisation of an
      &alpha;-bromo aluminium thioacetal was investigated under radical conditions. It
      was found that at low temperature, a radical fragmentation and rearrangement
      process occurs. A putative reaction mechanism involving a previously unreported
      aluminium templated thiol-ene step for the rearrangement process is presented.
      Cyclisation reactions of &alpha;-bromo thioesters and &alpha;-xanthate thioesters
      under radical mediated conditions furnished the desired thiolactones in moderate
      yields.

PMID- 29652814
TI  - Health Risk Assessment on Hazardous Ingredients in Household Deodorizing
      Products.
AB  - The inhalation of a water aerosol from a humidifier containing disinfectants has
      led to serious lung injuries in Korea. To promote the safe use of products, the
      Korean government enacted regulations on the chemicals in various consumer
      products that could have adverse health effects. Given the concern over the
      potential health risks associated with the hazardous ingredients in deodorizing
      consumer products, 17 ingredients were analyzed and assessed according to their
      health risk on 3 groups by the application type in 47 deodorizing products. The
      risk assessment study followed a stepwise procedure (e.g., collecting
      toxicological information, hazard identification/exposure assessment, and
      screening and detailed assessment for inhalation and dermal routes). The worst
      case scenario and maximum concentration determined by the product purpose and
      application type were used as the screening assessment. In a detailed assessment,
      the 75th exposure factor values were used to estimate the assumed reasonable
      exposure to ingredients. The exposed concentrations of seven ingredients were
      calculated. Due to limitation of toxicity information, butylated hydroxyl toluene
      for a consumer&rsquo;s exposure via the dermal route only was conducted for a
      detailed assessment. This study showed that the assessed ingredients have no
      health risks at their maximum concentrations in deodorizing products. This
      approach can be used to establish guidelines for ingredients that may pose
      inhalation and dermal hazards.

PMID- 29652815
TI  - Olfactory Dysfunction as a Global Biomarker for Sniffing out Alzheimer's Disease:
      A Meta-Analysis.
AB  - Cases of Alzheimer's disease (AD) are rising exponentially due to increasing
      global life expectancy. There are approximately 50 million sufferers worldwide,
      with prevalence rising most rapidly in low-income countries such as Africa and
      Asia. There is currently no definite diagnosis of AD until after death, thus an
      early biomarker for AD is urgently required in order to administer timelier and
      more effective interventions. Olfactory dysfunction (problems with the sense of
      smell) is one of the earliest, preclinical symptoms observed in AD. Olfaction is
      a promising early biomarker for use worldwide as it is easy, cheap to measure,
      and not reliant on specialist clinicians or laboratory analysis. We carried out a
      meta-analysis to determine the credibility of olfaction in diagnosing AD in the
      preclinical stages, by comparing olfaction in healthy controls against AD
      patients and patients with mild cognitive impairment (MCI). Data from 10 articles
      were subjected to two comparative meta-analyses. In the case of AD, the results
      illustrated that the overall magnitude of effect size was more apparent, d = 
      1.63, 95% CI [-1.95, -1.31], in comparison to that of MCI, d = -0.81, 95% CI [
      1.08, -0.55]. This shows that olfaction worsens progressively as patients
      progress from MCI to AD, highlighting the potential for olfactory dysfunction to
      identify AD in the preclinical stages prior to MCI.

PMID- 29652813
TI  - The Microenvironment in Epstein-Barr Virus-Associated Malignancies.
AB  - The Epstein-Barr virus (EBV) can cause a wide variety of cancers upon infection
      of different cell types and induces a highly variable composition of the tumor
      microenvironment (TME). This TME consists of both innate and adaptive immune
      cells and is not merely an aspecific reaction to the tumor cells. In fact, latent
      EBV-infected tumor cells utilize several specific mechanisms to form and shape
      the TME to their own benefit. These mechanisms have been studied largely in the
      context of EBV+ Hodgkin lymphoma, undifferentiated nasopharyngeal carcinoma, and
      EBV+ gastric cancer. This review describes the composition, immune escape
      mechanisms, and tumor cell promoting properties of the TME in these three
      malignancies. Mechanisms of susceptibility which regularly involve genes related
      to immune system function are also discussed, as only a small proportion of EBV
      infected individuals develops an EBV-associated malignancy.

PMID- 29652816
TI  - The Emergency Medical System in Greece: Opening Aeolus' Bag of Winds.
AB  - An Emergency Medical Service (EMS) system must encompass a spectrum of care, with
      dedicated pre-hospital and in-hospital medical facilities. It has to be organised
      in such a way as to include all necessary services&mdash;such as triage accurate
      initial assessment, prompt resuscitation, efficient management of emergency
      cases, and transport to definitive care. The global economic downturn has had a
      direct effect on the health sector and poses additional threats to the healthcare
      system. Greece is one of the hardest-hit countries. This manuscript aims to
      present the structure of the Greek EMS system and the impact of the current
      economic recession on it. Nowadays, primary care suffers major shortages in
      crucial equipment, unmet health needs, and ineffective central coordination.
      Patients are also facing economic limitations that lead to difficulties in using
      healthcare services. The multi-factorial problem of in-hospital EMS overcrowding
      is also evident and has been linked with potentially poorer clinical outcomes.
      Furthermore, the ongoing refugee crisis challenges the national EMS. Adoption of
      a triage scale, expansion of the primary care network, and an effective
      primary&ndash;hospital continuum of care are urgently needed in Greece to provide
      comprehensive, culturally competent, and high-quality health care.

PMID- 29652817
TI  - Selenium in Radiation Oncology-15 Years of Experiences in Germany.
AB  - Introduction: Se measurement and supplementation in radiation oncology is a
      controversial issue. The German Working Group Trace Elements and Electrolytes in
      Oncology (AKTE) has conducted a number of studies on this issue, which are
      summarized in this review. Strategies have been tested and developed, aiming to
      stratify the patients with a potential need for supplemental Se and how best to
      monitor Se supplementation with respect to health effects and risks. Methods: We
      analyzed blood and tissue Se-levels of different tumor patients (n = 512). Two
      randomized phase III clinical studies were conducted for testing a potential
      radioprotective effect of supplemental Se during radiation therapy in patients
      with uterine cancer (n = 81) and head and neck tumor patients (n = 39). Results:
      A relative Se deficit in whole blood or serum was detected in the majority of
      tumor patients (carcinomas of the uterus, head and neck, lung, rectal or prostate
      cancer). In prostate cancer, tissue Se concentrations were relatively elevated in
      the carcinoma centre as compared to the surrounding compartment or as compared to
      tumor samples from patients with benign prostatic hyperplasia. Adjuvant Se
      supplementation successfully corrected Se-deficiency in the patients analyzed and
      decreased radiotherapy-induced diarrhea in a randomized study of radiotherapy
      patients with carcinomas of the uterus. Survival data imply that Se
      supplementation did not interfere with radiation success. Some positive effects
      of supplemental Se in the prevention of ageusia (loss of taste) and dysphagia due
      to radiotherapy were noted in a second randomized trial in patients with head and
      neck cancer. We have not observed any adverse effects of supplemental Se in our
      studies. Conclusions: Se supplementation yielded promising results concerning
      radioprotection in tumor patients and should be considered as a promising
      adjuvant treatment option in subjects with a relative Se deficit.

PMID- 29652818
TI  - Beneficial Effects of Different Flavonoids on Vascular and Renal Function in L
      NAME Hypertensive Rats.
AB  - BACKGROUND: we have evaluated the antihypertensive effect of several flavonoid
      extracts in a rat model of arterial hypertension caused by chronic administration
      (6 weeks) of the nitric oxide synthesis inhibitor, L-NAME. METHODS: Sprague
      Dawley rats received L-NAME alone or L-NAME plus flavonoid-rich vegetal extracts
      (Lemon, Grapefruit + Bitter Orange, and Cocoa) or purified flavonoids (Apigenin
      and Diosmin) for 6 weeks. RESULTS: L-NAME treatment resulted in a marked
      elevation of blood pressure, and treatment with Apigenin, Lemon Extract, and
      Grapefruit + Bitter Orange extracts significantly reduced the elevated blood
      pressure of these animals. Apigenin and some of these flavonoids also ameliorated
      nitric oxide-dependent and -independent aortic vasodilation and elevated nitrite
      urinary excretion. End-organ abnormalities such as cardiac infarcts, hyaline
      arteriopathy and fibrinoid necrosis in coronary arteries and aorta were improved
      by these treatments, reducing the end-organ vascular damage. CONCLUSIONS: the
      flavonoids included in this study, specially apigenin, may be used as functional
      food ingredients with potential therapeutic benefit in arterial hypertension.

PMID- 29652820
TI  - Diet Quality and Nutrient Intake of Urban Overweight and Obese Primarily African
      American Older Adults with Osteoarthritis.
AB  - Diet quality may be a unique target for preventing and managing obesity-related
      osteoarthritis (OA). Using the Healthy Eating Index-2010 (HEI-2010), this study
      examined the nutrient intake and diet quality of 400 urban overweight and obese
      primarily African American older adults with self-reported lower extremity OA.
      Associations between sociodemographic and health-related factors and diet quality
      were explored. Participants (mean age 67.8 years, SD 5.9) were included. Habitual
      dietary intake was assessed using a food frequency questionnaire (FFQ). Nutrient
      intake and diet quality were calculated from the FFQ. Results indicated that diet
      quality needs improvement (HEI-2010: 66.3 (SD 10.5)). Age, body mass index,
      employment (multivariable model only), and OA severity (bivariate model only)
      were significant predictors of HEI-2010 total score in linear models. Mean
      intakes for fiber, calcium, and vitamin D were below recommendations, while
      percentage of calories as total fat exceeded recommendations. These findings can
      inform future dietary intervention trials and public health messaging for a sub
      population at a high risk for obesity-related OA.

PMID- 29652819
TI  - The When, What & How of Measuring Vitamin D Metabolism in Clinical Medicine.
AB  - We now have the ability to measure a number of different vitamin D metabolites
      with very accurate methods. The most abundant vitamin D metabolite, 25
      hydroxyvitamin D, is currently the best marker for overall vitamin D status and
      is therefore most commonly measured in clinical medicine. The added value of
      measuring metabolites beyond 25-hydroxyvitamin D, like 1,25-, and 24,25
      dihydroxyvitamin D is not broadly appreciated. Yet, in some more complicated
      cases, these metabolites may provide just the information needed for a legitimate
      diagnosis. The problem at present, is knowing when to measure, what to measure
      and how to measure. For 25-hydroxyvitamin D, the most frequently used automated
      immunoassays do not meet the requirements of today's standards for certain
      patient groups and liquid chromatography-tandem mass spectrometry is the desired
      method of choice in these individuals. The less frequently measured 1,25
      dihydroxyvitamin D metabolite enables us to identify a number of conditions,
      including 1alpha-hydroxylase deficiency, hereditary vitamin D-resistant rickets
      and a number of granulomatous diseases or lymphoproliferative diseases
      accompanied by hypercalcaemia. Furthermore, it discriminates between the FGF23
      mediated and non-FGF23-mediated hypophosphatemic syndromes. The 24,25
      dihydroxyvitamin D metabolite has proven its value in the diagnosis of idiopathic
      infantile hypercalcaemia and has the potential of having value in identifying
      other diseases. For both metabolites, the understanding of the origin of
      differences between assays is limited and requires further attention.
      Nonetheless, in every way, appropriate measurement of vitamin D metabolism in the
      clinical laboratory hinges eminently on the comprehension of the value of the
      different metabolites, and the importance of the choice of method.

PMID- 29652821
TI  - Who Are the Subjects with Gambling-Related Problems Requiring Treatment? A Study
      in Northern Italy.
AB  - BACKGROUND: This study analyzes data related to Hospital (HOS), Public Treatment
      Service Dedicated to Drug Addicts (SERD), or Community Mental Health Center
      (CMHC) clients with a first diagnosis of Pathological Gambling (PG) in the period
      2000/2016 in Northern Italy. The aims were to describe trends and characteristics
      of pathological gamblers (PGs) and to estimate the prevalence of other diagnoses
      before or after the diagnosis of PG. METHODS: Participants aged over 17 years
      with an ICD-9 or ICD-10 PG diagnosis were selected. RESULTS: 680 PGs were
      identified, mean age 47.4 years, 20% female, 13% non-natives, 30% had other
      mental disorders diagnoses, 9% had alcohol dependence syndrome, and 11% had drug
      dependence. Most participants with comorbid disorders were diagnosed before PG,
      with a more elevated prevalence regarding mental disorders. Almost seven years
      had elapsed on average between the first admission and the diagnosis of PG.
      CONCLUSIONS: The results of this study highlight a growing demand for PG
      treatment addressed not only to SERD, but also to psychiatric and hospital
      services, based on the increase in SERD attendance from 2013. Many of them had
      already been treated for mental health problems before, but their percentage
      remained costant over time.

PMID- 29652822
TI  - Taking a Gamble for High Rewards? Management Perspectives on the Value of Mental
      Health Peer Workers.
AB  - Mental health peer work is attracting growing interest and provides a potentially
      impactful method of service user involvement in mental health design and
      delivery, contributing to mental health reform. The need to effectively support
      this emerging workforce is consequently increasing. This study aimed to better
      understand the views of management in relation to peer work and specifically
      explores the value of peer work from the perspective of management. This
      qualitative research employed grounded theory methods. There were 29 participants
      in total, employed in both peer designated and non-peer designated management
      roles, in not for profit and public health organisations in Queensland,
      Australia. The value of peer work as described by participants is found to be
      partially dependent on practical supports and strategies from the organisation.
      There were high benefits for all facets of the organisation when effective
      recruitment and ongoing support for peer workers was prioritised and a higher
      perception of limitations when they were not. Due to some parallels, it may be
      useful to explore the potential for peer work to be conceptually and/or
      practically considered as a form of diversity and inclusion employment.

PMID- 29652823
TI  - Molecular Dynamics Simulations of Human Antimicrobial Peptide LL-37 in Model POPC
      and POPG Lipid Bilayers.
AB  - Cathelicidins are a large family of cationic antimicrobial peptides (AMPs) found
      in mammals with broad spectrum antimicrobial activity. LL-37 is the sole
      amphipathic alpha-helical AMP from human Cathelicidins family. In addition to its
      bactericidal capability, LL-37 has antiviral, anti-tumor, and immunoregulatory
      activity. Despite many experimental studies, its molecular mechanism of action is
      not yet fully understood. Here, we performed three independent molecular dynamics
      simulations (600 ns or more) of a LL-37 peptide in the presence of 256 lipid
      bilayers with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG) mimicking
      bacterial and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) mimicking
      mammalian membranes. We found that LL-37 can be quickly absorbed onto the POPG
      bilayer without loss of its helical conformation in the core region and with the
      helix lying in parallel to the bilayer. The POPG bilayer was deformed. In
      contrast, LL-37 is slower in reaching the POPC surface and loss much of its
      helical conformation during the interaction with the bilayer. LL-37 only
      partially entered the POPC bilayer without significant deformation of the
      membrane. The observed difference for different bilayers is largely due to the
      fact that LL-37 is positively charged, POPG is negatively charged, and POPC is
      neutral. Our simulation results demonstrated the initial stage of disruption of
      the bacterial membrane by LL-37 in atomic details. Comparison to experimental
      results on LL-37 and simulation studies in other systems was made.

PMID- 29652824
TI  - Full-Genome Characterization and Genetic Evolution of West African Isolates of
      Bagaza Virus.
AB  - Bagaza virus is a mosquito-borne flavivirus, first isolated in 1966 in Central
      African Republic. It has currently been identified in mosquito pools collected in
      the field in West and Central Africa. Emergence in wild birds in Europe and
      serological evidence in encephalitis patients in India raise questions on its
      genetic evolution and the diversity of isolates circulating in Africa. To better
      understand genetic diversity and evolution of Bagaza virus, we describe the full
      genome characterization of 11 West African isolates, sampled from 1988 to 2014.
      Parameters such as genetic distances, N-glycosylation patterns, recombination
      events, selective pressures, and its codon adaptation to human genes are
      assessed. Our study is noteworthy for the observation of N-glycosylation and
      recombination in Bagaza virus and provides insight into its Indian origin from
      the 13th century. Interestingly, evidence of Bagaza virus codon adaptation to
      human house-keeping genes is also observed to be higher than those of other
      flaviviruses well known in human infections. Genetic variations on genome of West
      African Bagaza virus could play an important role in generating diversity and may
      promote Bagaza virus adaptation to other vertebrates and become an important
      threat in human health.

PMID- 29652825
TI  - Fabrication of Sericin/Agrose Gel Loaded Lysozyme and Its Potential in Wound
      Dressing Application.
AB  - Sericin is a biomaterial resource for its significant biodegradability,
      biocompatibility, hydrophilicity, and reactivity. Designing a material with
      superabsorbent, antiseptic, and non-cytotoxic wound dressing properties is
      advantageous to reduce wound infection and promote wound healing. Herein, we
      propose an environment-friendly strategy to obtain an interpenetrating polymer
      network gel through blending sericin and agarose and freeze-drying. The
      physicochemical characterizations of the sericin/agarose gel including
      morphology, porosity, swelling behavior, crystallinity, secondary structure, and
      thermal property were well characterized. Subsequently, the lysozyme loaded
      sericin/agarose composite gel was successfully prepared by the solution
      impregnation method. To evaluate the potential of the lysozyme loaded
      sericin/agarose gel in wound dressing application, we analyzed the lysozyme
      loading and release, antimicrobial activity, and cytocompatibility of the
      resulting gel. The results showed the lysozyme loaded composite gel had high
      porosity, excellent water absorption property, and good antimicrobial activities
      against Escherichia coli and Staphylococcus aureus. Also, the lysozyme loaded gel
      showed excellent cytocompatibility on NIH3T3 and HEK293 cells. So, the lysozyme
      loaded sericin/agarose gel is a potential alternative biomaterial for wound
      dressing.

PMID- 29652826
TI  - Cardiovascular Mechanisms of Action of Anthocyanins May Be Associated with the
      Impact of Microbial Metabolites on Heme Oxygenase-1 in Vascular Smooth Muscle
      Cells.
AB  - Anthocyanins are reported to have cardio-protective effects, although their
      mechanisms of action remain elusive. We aimed to explore the effects of microbial
      metabolites common to anthocyanins and other flavonoids on vascular smooth muscle
      heme oxygenase-1 (HO-1) expression. Thirteen phenolic metabolites identified by
      previous anthocyanin human feeding studies, as well as 28 unique mixtures of
      metabolites and their known precursor structures were explored for their activity
      on HO-1 protein expression in rat aortic smooth muscle cells (RASMCs). No
      phenolic metabolites were active when treated in isolation; however, five
      mixtures of phenolic metabolites significantly increased HO-1 protein expression
      (127.4-116.6%, p <= 0.03). The present study demonstrates that phenolic
      metabolites of anthocyanins differentially affect HO-1 activity, often having
      additive, synergistic or nullifying effects.

PMID- 29652827
TI  - A Dual Bioconjugated Virus-Like Nanoparticle as a Drug Delivery System and
      Comparison with a pH-Responsive Delivery System.
AB  - Modifications of virus-like nanoparticles (VLNPs) using chemical conjugation
      techniques have brought the field of virology closer to nanotechnology. The huge
      surface area to volume ratio of VLNPs permits multiple copies of a targeting
      ligand and drugs to be attached per nanoparticle. By exploring the chemistry of
      truncated hepatitis B core antigen (tHBcAg) VLNPs, doxorubicin (DOX) was coupled
      covalently to the external surface of these nanoparticles via carboxylate groups.
      About 1600 DOX molecules were conjugated on each tHBcAg VLNP. Then, folic acid
      (FA) was conjugated to lysine residues of tHBcAg VLNPs to target the
      nanoparticles to cancer cells over-expressing folic acid receptor (FR). The
      result demonstrated that the dual bioconjugated tHBcAg VLNPs increased the
      accumulation and uptake of DOX in the human cervical and colorectal cancer cell
      lines compared with free DOX, resulting in enhanced cytotoxicity of DOX towards
      these cells. The fabrication of these dual bioconjugated nanoparticles is simple,
      and drugs can be easily conjugated with a high coupling efficacy to the VLNPs
      without any limitation with respect to the cargo's size or charge, as compared
      with the pH-responsive system based on tHBcAg VLNPs. These dual bioconjugated
      nanoparticles also have the potential to be modified for other combinatorial drug
      deliveries.

PMID- 29652828
TI  - Can a Simple Dietary Index Derived from a Sub-Set of Questionnaire Items Assess
      Diet Quality in a Sample of Australian Adults?
AB  - Large, longitudinal surveys often lack consistent dietary data, limiting the use
      of existing tools and methods that are available to measure diet quality. This
      study describes a method that was used to develop a simple index for ranking
      individuals according to their diet quality in a longitudinal study. The
      RESIDential Environments (RESIDE) project (2004-2011) collected dietary data in
      varying detail, across four time points. The most detailed dietary data were
      collected using a 24-item questionnaire at the final time point (n = 555; age >=
      25 years). At preceding time points, sub-sets of the 24 items were collected. A
      RESIDE dietary guideline index (RDGI) that was based on the 24-items was
      developed to assess diet quality in relation to the Australian Dietary
      Guidelines. The RDGI scores were regressed on the longitudinal sub-sets of six
      and nine questionnaire items at T4, from which two simple index scores (S-RDGI1
      and S-RDGI2) were predicted. The S-RDGI1 and S-RDGI2 showed reasonable agreement
      with the RDGI (Spearman's rho = 0.78 and 0.84; gross misclassification = 1.8%;
      correct classification = 64.9% and 69.7%; and, Cohen's weighted kappa = 0.58 and
      0.64, respectively). For all of the indices, higher diet quality was associated
      with being female, undertaking moderate to high amounts of physical activity, not
      smoking, and self-reported health. The S-RDGI1 and S-RDGI2 explained 62% and 73%
      of the variation in RDGI scores, demonstrating that a large proportion of the
      variability in diet quality scores can be captured using a relatively small sub
      set of questionnaire items. The methods described in this study can be applied
      elsewhere, in situations where limited dietary data are available, to generate a
      sample-specific score for ranking individuals according to diet quality.

PMID- 29652829
TI  - Molecular and Ultrastructural Mechanisms Underlying Yellow Dwarf Symptom
      Formation in Wheat after Infection of Barley Yellow Dwarf Virus.
AB  - Wheat (Tritium aestivum L.) production is essential for global food security.
      Infection of barley yellow dwarf virus-GAV (BYDV-GAV) results in wheat showing
      leaf yellowing and plant dwarfism symptom. To explore the molecular and
      ultrastructural mechanisms underlying yellow dwarf symptom formation in BYDV-GAV
      infected wheat, we investigated the chloroplast ultrastructure via transmission
      electron microscopy (TEM), examined the contents of the virus, H2O2, and
      chlorophyll in Zhong8601, and studied the comparative transcriptome through
      microarray analyses in the susceptible wheat line Zhong8601 after virus
      infection. TEM images indicated that chloroplasts in BYDV-GAV-infected Zhong8601
      leaf cells were fragmentized. Where thylakoids were not well developed, starch
      granules and plastoglobules were rare. Compared with mock-inoculated Zhong8601,
      chlorophyll content was markedly reduced, but the virus and H2O2 contents were
      significantly higher in BYDV-GAV-infected Zhong8601. The transcriptomic analyses
      revealed that chlorophyll biosynthesis and chloroplast related transcripts,
      encoding chlorophyll a/b binding protein, glucose-6-phosphate/phosphate
      translocator 2, and glutamyl-tRNA reductase 1, were down-regulated in BYDV-GAV
      infected Zhong8601. Some phytohormone signaling-related transcripts, including
      abscisic acid (ABA) signaling factors (phospholipase D alpha 1 and calcineurin B
      like protein 9) and nine ethylene response factors, were up-regulated.
      Additionally, reactive oxygen species (ROS)-related genes were transcriptionally
      regulated in BYDV-GAV infected Zhong8601, including three up-regulated
      transcripts encoding germin-like proteins (promoting ROS accumulation) and four
      down-regulated transcripts encoding peroxides (scavenging ROS). These results
      clearly suggest that the yellow dwarf symptom formation is mainly attributed to
      reduced chlorophyll content and fragmentized chloroplasts caused by down
      regulation of the chlorophyll and chloroplast biosynthesis related genes, ROS
      excessive accumulation, and precisely transcriptional regulation of the above
      mentioned ABA and ethylene signaling- and ROS-related genes in susceptible wheat
      infected by BYDV-GAV.

PMID- 29652831
TI  - Active (Opt-In) Consent Underestimates Mean BMI-z and the Prevalence of
      Overweight and Obesity Compared to Passive (Opt-Out) Consent. Evidence from the
      Healthy Together Victoria and Childhood Obesity Study.
AB  - : Background: Tracking population trends in childhood obesity and identifying
      target areas for prevention requires accurate prevalence data. This study
      quantified the magnitude of non-participation bias for mean Body Mass Index-z
      scores and overweight/obesity prevalence associated with low (opt-in) compared to
      high (opt-out) participation consent methodologies. Methods: Data arose from all
      Local Government Areas (LGAs) participating in the Healthy Together Victoria
      Childhood Obesity Study, Australia. Primary schools were randomly selected in
      2013 and 2014 and all Grades 4 and 6 students (aged approx. 9-12 years) were
      invited to participate via opt-in consent (2013) and opt-out consent (2014). For
      the opt-in wave N = 38 schools (recruitment rate (RR) 24.3%) and N = 856 students
      participated (RR 36.3%). For the opt-out wave N = 47 schools (RR 32%) and N =
      2557 students participated (RR 86.4%). OUTCOMES: differences between opt-in and
      opt-out sample estimates (bias) for mean BMI-z, prevalence of overweight/obesity
      and obesity (alone). Standardized bias (Std bias) estimates defined as
      bias/standard error are reported for BMI-z. Results: The results demonstrate
      strong evidence of non-participation bias for mean BMI-z overall (Std bias = 
      4.5, p < 0.0001) and for girls (Std bias = -5.4, p < 0.0001), but not for boys
      (Std bias = -1.1, p = 0.15). The opt-in strategy underestimated the overall
      population prevalence of overweight/obesity and obesity by -5.4 and -4.5
      percentage points respectively (p < 0.001 for both). Significant underestimation
      was seen in girls, but not for boys. Conclusions: Opt-in consent underestimated
      prevalence of childhood obesity, particularly in girls. Prevalence, monitoring
      and community intervention studies on childhood obesity should move to opt-out
      consent processes for better scientific outcomes.

PMID- 29652833
TI  - A Lipophilic IR-780 Dye-Encapsulated Zwitterionic Polymer-Lipid Micellar
      Nanoparticle for Enhanced Photothermal Therapy and NIR-Based Fluorescence Imaging
      in a Cervical Tumor Mouse Model.
AB  - To prolong blood circulation and avoid the triggering of immune responses,
      nanoparticles in the bloodstream require conjugation with polyethylene glycol
      (PEG). However, PEGylation hinders the interaction between the nanoparticles and
      the tumor cells and therefore limits the applications of PEGylated nanoparticles
      for therapeutic drug delivery. To overcome this limitation, zwitterionic
      materials can be used to enhance the systemic blood circulation and tumor
      specific delivery of hydrophobic agents such as IR-780 iodide dye for
      photothermal therapy. Herein, we developed micellar nanoparticles using the
      amphiphilic homopolymer poly(12-(methacryloyloxy)dodecyl phosphorylcholine) (PCB
      lipid) synthesized via reversible addition-fragmentation chain transfer (RAFT)
      polymerization. The PCB-lipid can self-assemble into micelles and encapsulate IR
      780 dye (PCB-lipid-IR-780). Our results demonstrated that PCB-lipid-IR-780
      nanoparticle (NP) exhibited low cytotoxicity and remarkable photothermal
      cytotoxicity to cervical cancer cells (TC-1) upon near-infrared (NIR) laser
      irradiation. The biodistribution of PCB-lipid-IR-780 showed higher accumulation
      of PCB-lipid-IR-780 than that of free IR-780 in the TC-1 tumor. Furthermore,
      following NIR laser irradiation of the tumor region, the PCB-lipid-IR-780
      accumulated in the tumor facilitated enhanced tumor ablation and subsequent tumor
      regression in the TC-1 xenograft model. Hence, these zwitterionic polymer-lipid
      hybrid micellar nanoparticles show great potential for cancer theranostics and
      might be beneficial for clinical applications.

PMID- 29652834
TI  - Easy-to-Build Textile Pressure Sensor.
AB  - This article presents the design, construction, and evaluation of an easy-to
      build textile pressure resistive sensor created from low-cost conventional anti
      static sheets and conductive woven fabrics. The sensor can be built quickly using
      standard household tools, and its thinness makes it especially suitable for
      wearable applications. Five sensors constructed under such conditions were
      evaluated, presenting a stable and linear characteristic in the range 1 to 70
      kPa. The linear response was modeled and fitted for each sensor individually for
      comparison purposes, confirming a low variability due to the simple manufacturing
      process. Besides, the recovery times of the sensors were measured for pressures
      in the linear range, observing, for example, an average time of 1 s between the
      moment in which a pressure of 8 kPa was no longer applied, and the resistance
      variation at the 90% of its nominal value. Finally, we evaluated the proposed
      sensor design on a classroom application consisting of a smart glove that
      measured the pressure applied by each finger. From the evaluated characteristics,
      we concluded that the proposed design is suitable for didactic, healthcare and
      lifestyle applications in which the sensing of pressure variations, e.g., for
      activity assessment, is more valuable than accurate pressure sensing.

PMID- 29652835
TI  - Fabrication of Flexible Microneedle Array Electrodes for Wearable Bio-Signal
      Recording.
AB  - Laser-direct writing (LDW) and magneto-rheological drawing lithography (MRDL)
      have been proposed for the fabrication of a flexible microneedle array electrode
      (MAE) for wearable bio-signal monitoring. Conductive patterns were directly
      written onto the flexible polyethylene terephthalate (PET) substrate by LDW. The
      microneedle array was rapidly drawn and formed from the droplets of curable
      magnetorheological fluid with the assistance of an external magnetic field by
      MRDL. A flexible MAE can maintain a stable contact interface with curved human
      skin due to the flexibility of the PET substrate. Compared with Ag/AgCl
      electrodes and flexible dry electrodes (FDE), the electrode-skin interface
      impedance of flexible MAE was the minimum even after a 50-cycle bending test.
      Flexible MAE can record electromyography (EMG), electroencephalography (EEG) and
      static electrocardiography (ECG) signals with good fidelity. The main features of
      the dynamic ECG signal recorded by flexible MAE are the most distinguishable with
      the least moving artifacts. Flexible MAE is an attractive candidate electrode for
      wearable bio-signal monitoring.

PMID- 29652836
TI  - A Fast and On-Machine Measuring System Using the Laser Displacement Sensor for
      the Contour Parameters of the Drill Pipe Thread.
AB  - The inconvenient loading and unloading of a long and heavy drill pipe gives rise
      to the difficulty in measuring the contour parameters of its threads at both
      ends. To solve this problem, in this paper we take the SCK230 drill pipe thread
      repairing machine tool as a carrier to design and achieve a fast and on-machine
      measuring system based on a laser probe. This system drives a laser displacement
      sensor to acquire the contour data of a certain axial section of the thread by
      using the servo function of a CNC machine tool. To correct the sensor's
      measurement errors caused by the measuring point inclination angle, an
      inclination error model is built to compensate data in real time. To better
      suppress random error interference and ensure real contour information, a new
      wavelet threshold function is proposed to process data through the wavelet
      threshold denoising. Discrete data after denoising is segmented according to the
      geometrical characteristics of the drill pipe thread, and the regression model of
      the contour data in each section is fitted by using the method of weighted total
      least squares (WTLS). Then, the thread parameters are calculated in real time to
      judge the processing quality. Inclination error experiments show that the
      proposed compensation model is accurate and effective, and it can improve the
      data acquisition accuracy of a sensor. Simulation results indicate that the
      improved threshold function is of better continuity and self-adaptability, which
      makes sure that denoising effects are guaranteed, and, meanwhile, the complete
      elimination of real data distorted in random errors is avoided. Additionally,
      NC50 thread-testing experiments show that the proposed on-machine measuring
      system can complete the measurement of a 25 mm thread in 7.8 s, with a
      measurement accuracy of +/-8 MUm and repeatability limit <= 4 MUm (high
      repeatability), and hence the accuracy and efficiency of measurement are both
      improved.

PMID- 29652832
TI  - Sympathetic Nerve Hyperactivity in the Spleen: Causal for Nonpathogenic-Driven
      Chronic Immune-Mediated Inflammatory Diseases (IMIDs)?
AB  - Immune-Mediated Inflammatory Diseases (IMIDs) is a descriptive term coined for an
      eclectic group of diseases or conditions that share common inflammatory pathways,
      and for which there is no definitive etiology. IMIDs affect the elderly most
      severely, with many older individuals having two or more IMIDs. These diseases
      include, but are not limited to, type-1 diabetes, obesity, hypertension, chronic
      pulmonary disease, coronary heart disease, inflammatory bowel disease, and
      autoimmunity, such as rheumatoid arthritis (RA), Sjogren's syndrome, systemic
      lupus erythematosus, psoriasis, psoriatic arthritis, and multiple sclerosis.
      These diseases are ostensibly unrelated mechanistically, but increase in
      frequency with age and share chronic systemic inflammation, implicating major
      roles for the spleen. Chronic systemic and regional inflammation underlies the
      disease manifestations of IMIDs. Regional inflammation and immune dysfunction
      promotes targeted end organ tissue damage, whereas systemic inflammation
      increases morbidity and mortality by affecting multiple organ systems. Chronic
      inflammation and skewed dysregulated cell-mediated immune responses drive many of
      these age-related medical disorders. IMIDs are commonly autoimmune-mediated or
      suspected to be autoimmune diseases. Another shared feature is dysregulation of
      the autonomic nervous system and hypothalamic pituitary adrenal (HPA) axis. Here,
      we focus on dysautonomia. In many IMIDs, dysautonomia manifests as an imbalance
      in activity/reactivity of the sympathetic and parasympathetic divisions of the
      autonomic nervous system (ANS). These major autonomic pathways are essential for
      allostasis of the immune system, and regulating inflammatory processes and innate
      and adaptive immunity. Pathology in ANS is a hallmark and causal feature of all
      IMIDs. Chronic systemic inflammation comorbid with stress pathway dysregulation
      implicate neural-immune cross-talk in the etiology and pathophysiology of IMIDs.
      Using a rodent model of inflammatory arthritis as an IMID model, we report
      disease-specific maladaptive changes in beta2-adrenergic receptor (AR) signaling
      from protein kinase A (PKA) to mitogen activated protein kinase (MAPK) pathways
      in the spleen. Beta2-AR signal "shutdown" in the spleen and switching from PKA to
      G-coupled protein receptor kinase (GRK) pathways in lymph node cells drives
      inflammation and disease advancement. Based on these findings and the existing
      literature in other IMIDs, we present and discuss relevant literature that
      support the hypothesis that unresolvable immune stimulation from chronic
      inflammation leads to a maladaptive disease-inducing and perpetuating sympathetic
      response in an attempt to maintain allostasis. Since the role of sympathetic
      dysfunction in IMIDs is best studied in RA and rodent models of RA, this IMID is
      the primary one used to evaluate data relevant to our hypothesis. Here, we review
      the relevant literature and discuss sympathetic dysfunction as a significant
      contributor to the pathophysiology of IMIDs, and then discuss a novel target for
      treatment. Based on our findings in inflammatory arthritis and our understanding
      of common inflammatory process that are used by the immune system across all
      IMIDs, novel strategies to restore SNS homeostasis are expected to provide safe,
      cost-effective approaches to treat IMIDs, lower comorbidities, and increase
      longevity.

PMID- 29652837
TI  - Fabrication of Composite Microneedle Array Electrode for Temperature and Bio
      Signal Monitoring.
AB  - Body temperature and bio-signals are important health indicators that reflect the
      human health condition. However, monitoring these indexes is inconvenient and
      time-consuming, requires various instruments, and needs professional skill. In
      this study, a composite microneedle array electrode (CMAE) was designed and
      fabricated. It simultaneously detects body temperature and bio-signals. The CMAE
      consists of a 6 * 6 microneedles array with a height of 500 MUm and a base
      diameter of 200 MUm. Multiple insertion experiments indicate that the CMAE
      possesses excellent mechanical properties. The CMAE can pierce porcine skin 100
      times without breaking or bending. A linear calibration relationship between
      temperature and voltage are experimentally obtained. Armpit temperature (35.8 
      degrees C) and forearm temperature (35.3  degrees C) are detected with the CMAE,
      and the measurements agree well with the data acquired with a clinical
      thermometer. Bio-signals including EII, ECG, and EMG are recorded and compared
      with those obtained by a commercial Ag/AgCl electrode. The CMAE continuously
      monitors bio-signals and is more convenient to apply because it does not require
      skin preparation and gel usage. The CMAE exhibits good potential for continuous
      and repetitive monitoring of body temperature and bio-signals.

PMID- 29652838
TI  - Super-Resolution for "Jilin-1" Satellite Video Imagery via a Convolutional
      Network.
AB  - Super-resolution for satellite video attaches much significance to earth
      observation accuracy, and the special imaging and transmission conditions on the
      video satellite pose great challenges to this task. The existing deep
      convolutional neural-network-based methods require pre-processing or post
      processing to be adapted to a high-resolution size or pixel format, leading to
      reduced performance and extra complexity. To this end, this paper proposes a five
      layer end-to-end network structure without any pre-processing and post
      processing, but imposes a reshape or deconvolution layer at the end of the
      network to retain the distribution of ground objects within the image. Meanwhile,
      we formulate a joint loss function by combining the output and high-dimensional
      features of a non-linear mapping network to precisely learn the desirable mapping
      relationship between low-resolution images and their high-resolution
      counterparts. Also, we use satellite video data itself as a training set, which
      favors consistency between training and testing images and promotes the method's
      practicality. Experimental results on "Jilin-1" satellite video imagery show that
      this method demonstrates a superior performance in terms of both visual effects
      and measure metrics over competing methods.

PMID- 29652839
TI  - Selenium-Rich Ricegrass Juice Improves Antioxidant Properties and Nitric Oxide
      Inhibition in Macrophage Cells.
AB  - Ricegrass juice (Oryza sativa L.) was introduced as a functional food as the
      consumption of sprouts or seedlings has been claimed to provide high nutritive
      value. Selenium (Se) is a trace mineral that plays a key role in the human
      antioxidation scheme. Supplementation of Se into plants is one strategy to
      enhance plant bioactivities, and the consumption of Se plant foods may confer
      superior health benefits. In this study, ricegrass juice extract was analyzed for
      its major phenolic components. The effect of ricegrass juice extracts bio
      fortified with 0, 10 and 40 mg Se/L named as RG0, RG10, and RG40, respectively,
      were investigated for a percentage of cell viability, changes of endogenous
      antioxidant enzymes, lipid peroxidation, and nitric oxide inhibition in RAW264.7
      macrophage cells. Flavone glycosides, namely chrysoeriol arabinosyl arabinoside
      derivatives, were found to be the foremost bioactive components in ricegrass
      juice extract indicated by UHPLC-MS. The results of cell culture assessment
      revealed that RG40 showed an ability to promote macrophage cell proliferation at
      low concentration. Ricegrass juice extract in all treatments possessed the
      ability to reduce malondialdehyde content, which may be regarded as the
      bioactivity of phenolic compounds. Moreover, Se also played a role in this effect
      since RG40 showed the greatest ability via increasing the level of GPx enzyme. It
      was also discovered that phenolic compounds in the extracts played a role in
      inhibiting nitric oxide in LPS-induced RAW264.7 cells. Furthermore, RG40
      expressed significantly higher NO inhibition properties at IC50 118.76 ug/mL
      compared to RG0 and RG10, at 147.02 and 147.73 ug/mL, respectively. Se bio
      fortified ricegrass juice could be considered as a new potent functional food
      that can lower the risk of oxidative stress and chronic inflammation diseases.

PMID- 29652830
TI  - Colorectal cancer: genetic abnormalities, tumor progression, tumor heterogeneity,
      clonal evolution and tumor-initiating cells.
AB  - Colon cancer is the third most common cancer worldwide. Most colorectal cancer
      occurrences are sporadic, not related to genetic predisposition or family
      history; however, 20-30% of patients with colorectal cancer have a family history
      of colorectal cancer and 5% of these tumors arise in the setting of a Mendelian
      inheritance syndrome. In many patients, the development of a colorectal cancer is
      preceded by a benign neoplastic lesion: either an adenomatous polyp or a serrated
      polyp. Studies carried out in the last years have characterized the main
      molecular alterations occurring in colorectal cancers, showing that the tumor of
      each patient displays from two to eight driver mutations. The ensemble of
      molecular studies, including gene expression studies, has led to two proposed
      classifications of colorectal cancers, with the identification of four/five non
      overlapping groups. The homeostasis of the rapidly renewing intestinal epithelium
      is ensured by few stem cells present at the level of the base of intestinal
      crypts. Various experimental evidence suggests that colorectal cancers may derive
      from the malignant transformation of intestinal stem cells or of intestinal cells
      that acquire stem cell properties following malignant transformation. Colon
      cancer stem cells seem to be involved in tumor chemoresistance, radioresistance
      and relapse.

PMID- 29652840
TI  - Verifying Safety Messages Using Relative-Time and Zone Priority in Vehicular Ad
      Hoc Networks.
AB  - In high-density road networks, with each vehicle broadcasting multiple messages
      per second, the arrival rate of safety messages can easily exceed the rate at
      which digital signatures can be verified. Since not all messages can be verified,
      algorithms for selecting which messages to verify are required to ensure that
      each vehicle receives appropriate awareness about neighbouring vehicles. This
      paper presents a novel scheme to select important safety messages for
      verification in vehicular ad hoc networks (VANETs). The proposed scheme uses
      location and direction of the sender, as well as proximity and relative-time
      between vehicles, to reduce the number of irrelevant messages verified (i.e.,
      messages from vehicles that are unlikely to cause an accident). Compared with
      other existing schemes, the analysis results show that the proposed scheme can
      verify messages from nearby vehicles with lower inter-message delay and reduced
      packet loss and thus provides high level of awareness of the nearby vehicles.

PMID- 29652841
TI  - Electrochemically-Driven Insertion of Biological Nanodiscs into Solid State
      Membrane Pores as a Basis for "Pore-In-Pore" Membranes.
AB  - Nanoporous membranes are of increasing interest for many applications, such as
      molecular filters, biosensors, nanofluidic logic and energy conversion devices.
      To meet high-quality standards, e.g., in molecular separation processes,
      membranes with well-defined pores in terms of pore diameter and chemical
      properties are required. However, the preparation of membranes with narrow pore
      diameter distributions is still challenging. In the work presented here, we
      demonstrate a strategy, a "pore-in-pore" approach, where the conical pores of a
      solid state membrane produced by a multi-step top-down lithography procedure are
      used as a template to insert precisely-formed biomolecular nanodiscs with exactly
      defined inner and outer diameters. These nanodiscs, which are the building blocks
      of tobacco mosaic virus-deduced particles, consist of coat proteins, which self
      assemble under defined experimental conditions with a stabilizing short RNA. We
      demonstrate that the insertion of the nanodiscs can be driven either by diffusion
      due to a concentration gradient or by applying an electric field along the cross
      section of the solid state membrane. It is found that the electrophoresis-driven
      insertion is significantly more effective than the insertion via the
      concentration gradient.

PMID- 29652842
TI  - Association between Modified Body Mass Index and 30-Day and 1-Year Mortality
      after Intensive Care Unit Admission: A Retrospective Cohort Study.
AB  - Because conventional body mass index (cBMI) does not reflect fluid accumulation,
      modified BMI (mBMI, serum albumin multiplied by cBMI) is a more accurate measure
      of malnutrition status. This study aimed to determine whether mortality after
      intensive care unit (ICU) admission was associated with cBMI, mBMI, and/or serum
      albumin levels. The medical records of patients who were admitted to a tertiary
      hospital ICU between 1 January 2012 and 31 July 2016 were retrospectively
      reviewed. In total, 6169 ICU-admitted patients were included in the analyses.
      Multivariate Cox regression analyses revealed that low cBMI, mBMI and albumin
      level were significantly associated with 30-day and 1-year mortality after ICU
      admission (hazard ratio < 1.0, p < 0.05). The adjusted area under the curve (AUC)
      of mBMI for 1-year mortality was significantly higher than that of cBMI (p <
      0.001), but not significantly different from that of albumin level (p = 0.098).
      Low values of mBMI, cBMI and albumin were independently associated with 30-day
      and 1-year mortality after ICU admission. Combining cBMI and albumin (mBMI) did
      not increase the validity of the AUC of albumin for 1-year mortality after ICU
      admission. Our study showed that serum albumin alone, rather than mBMI (combining
      cBMI), is recommended in predicting mortality among ICU patients.

PMID- 29652843
TI  - iAPSL-IF: Identification of Apoptosis Protein Subcellular Location Using
      Integrative Features Captured from Amino Acid Sequences.
AB  - Apoptosis proteins (APs) control normal tissue homeostasis by regulating the
      balance between cell proliferation and death. The function of APs is strongly
      related to their subcellular location. To date, computational methods have been
      reported that reliably identify the subcellular location of APs, however, there
      is still room for improvement of the prediction accuracy. In this study, we
      developed a novel method named iAPSL-IF (identification of apoptosis protein
      subcellular location-integrative features), which is based on integrative
      features captured from Markov chains, physicochemical property matrices, and
      position-specific score matrices (PSSMs) of amino acid sequences. The matrices
      with different lengths were transformed into fixed-length feature vectors using
      an auto cross-covariance (ACC) method. An optimal subset of the features was
      chosen using a recursive feature elimination (RFE) algorithm method, and the
      sequences with these features were trained by a support vector machine (SVM)
      classifier. Based on three datasets ZD98, CL317, and ZW225, the iAPSL-IF was
      examined using a jackknife cross-validation test. The resulting data showed that
      the iAPSL-IF outperformed the known predictors reported in the literature: its
      overall accuracy on the three datasets was 98.98% (ZD98), 94.95% (CL317), and
      97.33% (ZW225), respectively; the Matthews correlation coefficient, sensitivity,
      and specificity for several classes of subcellular location proteins (e.g.,
      membrane proteins, cytoplasmic proteins, endoplasmic reticulum proteins, nuclear
      proteins, and secreted proteins) in the datasets were 0.92-1.0, 94.23-100%, and
      97.07-100%, respectively. Overall, the results of this study provide a high
      throughput and sequence-based method for better identification of the subcellular
      location of APs, and facilitates further understanding of programmed cell death
      in organisms.

PMID- 29652844
TI  - gga-miR-451 Negatively Regulates Mycoplasma gallisepticum (HS Strain)-Induced
      Inflammatory Cytokine Production via Targeting YWHAZ.
AB  - Mycoplasma gallisepticum (MG) is the most economically significant mycoplasma
      pathogen of poultry that causes chronic respiratory disease (CRD) in chickens.
      Although miRNAs have been identified as a major regulator effect on inflammatory
      response, it is largely unclear how they regulate MG-induced inflammation. The
      aim of this study was to investigate the functional roles of gga-miR-451 and
      identify downstream targets regulated by gga-miR-451 in MG infection of chicken.
      We found that the expression of gga-miR-451 was significantly up-regulated during
      MG infection of chicken embryo fibroblast cells (DF-1) and chicken embryonic
      lungs. Overexpression of gga-miR-451 decreased the MG-induced inflammatory
      cytokine production, including tumor necrosis factor-alpha (TNF-alpha),
      interleukin-1beta (IL-1beta), and interleukin-6 (IL-6), whereas inhibition of gga
      miR-451 had the opposite effect. Gene expression data combined with luciferase
      reporter assays demonstrated that tyrosine3-monooxygenase/tryptophan5
      monooxygenase activation protein zeta (YWHAZ) was identified as a direct target
      of gga-miR-451 in the context of MG infection. Furthermore, upregulation of gga
      miR-451 significantly inhibited the MG-infected DF-1 cells proliferation, induced
      cell-cycle arrest, and promoted apoptosis. Collectively, our results demonstrate
      that gga-miR-451 negatively regulates the MG-induced production of inflammatory
      cytokines via targeting YWHAZ, inhibits the cell cycle progression and cell
      proliferation, and promotes cell apoptosis. This study provides a better
      understanding of the molecular mechanisms of MG infection.

PMID- 29652846
TI  - Friction Stir Processing of Copper-Coated SiC Particulate-Reinforced Aluminum
      Matrix Composite.
AB  - In the present work, we proposed a novel friction stir processing (FSP) to
      produce a locally reinforced aluminum matrix composite (AMC) by stirring copper
      coated SiC particulate reinforcement into Al6061 alloy matrix. Electroless
      plating process was applied to deposit the copper surface coating on the SiC
      particulate reinforcement for the purpose of improving the interfacial adhesion
      between SiC particles and Al matrix. The core-shell SiC structure provides a
      layer for the atomic diffusion between aluminum and copper to enhance the
      cohesion between reinforcing particles and matrix on one hand, the dispersion of
      fine copper in the Al matrix during FSP provides further dispersive strengthening
      and solid solution strengthening, on the other hand. Hardness distribution and
      tensile results across the stir zone validated the novel concept in improving the
      mechanical properties of AMC that was realized via FSP. Optical microscope (OM)
      and Transmission Electron Microscopy (TEM) investigations were conducted to
      investigate the microstructure. Energy dispersive spectrometer (EDS), electron
      probe micro-analyzer (EPMA), and X-ray diffraction (XRD) were explored to analyze
      the atomic inter-diffusion and the formation of intermetallic at interface. The
      possible strengthening mechanisms of the AMC containing Cu-coated SiC particulate
      reinforcement were interpreted. The concept of strengthening developed in this
      work may open a new way of fabricating of particulate reinforced metal matrix
      composites.

PMID- 29652845
TI  - Differential Effects of Linkers on the Activity of Amphiphilic Tobramycin
      Antifungals.
AB  - As the threat associated with fungal infections continues to rise and the
      availability of antifungal drugs remains a concern, it becomes obvious that the
      need to bolster the antifungal armamentarium is urgent. Building from our
      previous findings of tobramycin (TOB) derivatives with antifungal activity, we
      further investigate the effects of various linkers on the biological activity of
      these aminoglycosides. Herein, we analyze how thioether, sulfone, triazole,
      amide, and ether functionalities affect the antifungal activity of alkylated TOB
      derivatives against 22 Candida, Cryptococcus, and Aspergillus species. We also
      evaluate their impact on the hemolysis of murine erythrocytes and the
      cytotoxicity against mammalian cell lines. While the triazole linker appears to
      confer optimal activity overall, all of the linkers incorporated into the TOB
      derivatives resulted in compounds that are very effective against the
      Cryptococcus neoformans species, with MIC values ranging from 0.48 to 3.9 MUg/mL.

PMID- 29652847
TI  - Comparative Phytonutrient Analysis of Broccoli By-Products: The Potentials for
      Broccoli By-Product Utilization.
AB  - The phytonutrient concentrations of broccoli (Brassica oleracea var. italica)
      florets, stems, and leaves were compared to evaluate the value of stem and leaf
      by-products as a source of valuable nutrients. Primary metabolites, including
      amino acids, organic acids, and sugars, as well as glucosinolates, carotenoids,
      chlorophylls, vitamins E and K, essential mineral elements, total phenolic
      content, antioxidant activity, and expression of glucosinolate biosynthesis and
      hydrolysis genes were quantified from the different broccoli tissues. Broccoli
      florets had higher concentrations of amino acids, glucoraphanin, and
      neoglucobrassicin compared to other tissues, whereas leaves were higher in
      carotenoids, chlorophylls, vitamins E and K, total phenolic content, and
      antioxidant activity. Leaves were also good sources of calcium and manganese
      compared to other tissues. Stems had the lowest nitrile formation from
      glucosinolate. Each tissue exhibited specific core gene expression profiles
      supporting glucosinolate metabolism, with different gene homologs expressed in
      florets, stems, and leaves, which suggests that tissue-specific pathways function
      to support primary and secondary metabolic pathways in broccoli. This
      comprehensive nutrient and bioactive compound profile represents a useful
      resource for the evaluation of broccoli by-product utilization in the human diet,
      and as feedstocks for bioactive compounds for industry.

PMID- 29652848
TI  - Excellent Tribological Properties of Lower Reduced Graphene Oxide Content Copper
      Composite by Using a One-Step Reduction Molecular-Level Mixing Process.
AB  - Reduced graphene oxide (RGO) composite copper matrix powders were fabricated
      successfully by using a modified molecular-level mixing (MLM) method. Divalent
      copper ions (Cu2+) were adsorbed in oxygen functional groups of graphene oxide
      (GO) as a precursor, then were reduced simultaneously by one step chemical
      reduction. RGO showed a distribution converting from a random to a three
      dimensional network in the copper matrix when its content increased to above 1.0
      wt.% The tribological tests indicated that the friction coefficient of the
      composite with 1.0 wt.% RGO decreased markedly from 0.6 to 0.07 at an applied
      load of 10 N, and the wear rate was about one-third of pure copper. The excellent
      tribological properties were attributed to a three-dimensional and uniform
      distribution, which contributes to improving toughness and adhesion strength.

PMID- 29652850
TI  - Spherical alpha-MnO2 Supported on N-KB as Efficient Electrocatalyst for Oxygen
      Reduction in Al-Air Battery.
AB  - Traditional noble metal platinum (Pt) is regarded as a bifunctional oxygen
      catalyst due to its highly catalytic efficiency, but its commercial availability
      and application is often restricted by high cost. Herein, a cheap and effective
      catalyst mixed with alpha-MnO2 and nitrogen-doped Ketjenblack (N-KB) (denoted as
      MnO2-SM150-0.5) is examined as a potential electrocatalyst in oxygen reduction
      reactions (ORR) and oxygen evolution reactions (OER). This alpha-MnO2 is prepared
      by redox reaction between K2S2O8 and MnSO4 in acid conditions with a facile
      hydrothermal process (named the SM method). As a result, MnO2-SM150-0.5 exhibits
      a good catalytic performance for ORR in alkaline solution, and this result is
      comparable to a Pt/C catalyst. Moreover, this catalyst also shows superior
      durability and methanol tolerance compared with a Pt/C catalyst. It also displays
      a discharge voltage (~1.28 V) at a discharge density of 50 mA cm-2 in homemade Al
      air batteries that is higher than commercial 20% Pt/C (~1.19 V). The superior
      electrocatalytic performance of MnO2-SM150-0.5 could be attributed to its higher
      Mn3+/Mn4+ ratio and the synergistic effect between MnO2 and the nitrogen-doped
      KB. This study provides a novel strategy for the preparation of an MnO2-based
      composite electrocatalyst.

PMID- 29652849
TI  - Update on Marine Carbohydrate Hydrolyzing Enzymes: Biotechnological Applications.
AB  - After generating much interest in the past as an aid in solving structural
      problems for complex molecules such as polysaccharides, carbohydrate-hydrolyzing
      enzymes of marine origin still appear as interesting biocatalysts for a range of
      useful applications in strong interdisciplinary fields such as green chemistry
      and similar domains. The multifaceted fields in which these enzymes are of
      interest and the scarce number of original articles in literature prompted us to
      provide the specialized analysis here reported. General considerations from
      modern (2016-2017 interval time) review articles are at start of this manuscript;
      then it is subsequently organized in sections according to particular biopolymers
      and original research articles are discussed. Literature sources like the Science
      Direct database with an optimized W/in search, and the Espacenet patent database
      were used.

PMID- 29652851
TI  - The Work Softening Behavior of Pure Mg Wire during Cold Drawing.
AB  - We performed multiple-pass cold drawing for pure Mg wire which showed excellent
      formability (~138% accumulative true strain) at room temperature. Different from
      the continuous work hardening occurring during cold drawing of Mg alloy wires,
      for pure Mg, an initially rapid increase in hardness and strength was followed by
      significant work softening and finally reached a steady-state level,
      approximately 40~45 HV. The work softening can be attributed to the dynamic
      recovery and recrystallization of pure Mg at room temperature. Meanwhile, an
      abrupt change in texture component also was detected with the transition from
      work hardening to softening in the strain range of 28~34%. During the whole
      drawing, the strongest texture component gradually transformed from as-extruded
      basal to <10 1 - 0> fiber (~28% accumulative true strain), and then rapidly
      returned to the weak basal texture.

PMID- 29652852
TI  - The Effect of PM2.5 from Household Combustion on Life Expectancy in Sub-Saharan
      Africa.
AB  - Household fuel combustion, especially using solid combustibles (biomass and
      fossil fuels), for cooking and other activities produces emissions that
      contribute to concentrations of indoor as well as outdoor air pollutants such as
      particulate matter with diameter smaller than 2.5 MUm (PM2.5) that deteriorate
      health and likely affect life expectancy (LEX). This study investigates the
      impact of PM2.5 from household combustion on LEX considering several covariates
      while controlling for ambient PM2.5 generated by other sectors. The generalized
      method of moments (GMM) model and the panel cointegration model were applied to a
      dataset of 43 Sub-Saharan Africa (SSA) countries over the time period of 1995
      2010. Both approaches provide similar results indicating that household PM2.5 is
      significantly and negatively associated with higher aggregate LEX in the long
      run, and, to a greater degree for female's. Also, among the control variables,
      PM2.5 from the transport sector has a greater influence on male's LEX. Thus,
      efforts should be combined to reduce household PM2.5 since lower levels are
      associated with increased LEX.

PMID- 29652853
TI  - Electromagnetic Nanoparticles for Sensing and Medical Diagnostic Applications.
AB  - A modeling and design approach is proposed for nanoparticle-based electromagnetic
      devices. First, the structure properties were analytically studied using
      Maxwell's equations. The method provides us a robust link between nanoparticles
      electromagnetic response (amplitude and phase) and their geometrical
      characteristics (shape, geometry, and dimensions). Secondly, new designs based on
      "metamaterial" concept are proposed, demonstrating great performances in terms of
      wide-angle range functionality and multi/wide behavior, compared to conventional
      devices working at the same frequencies. The approach offers potential
      applications to build-up new advanced platforms for sensing and medical
      diagnostics. Therefore, in the final part of the article, some practical examples
      are reported such as cancer detection, water content measurements, chemical
      analysis, glucose concentration measurements and blood diseases monitoring.

PMID- 29652854
TI  - Phylogenetic Analysis and Pathogenicity Assessment of the Emerging Recombinant
      Subgroup K of Avian Leukosis Virus in South China.
AB  - In recent years, cases of avian leukosis virus (ALV) infection have become more
      frequent in China. We isolated 6 ALV strains from yellow feather broiler breeders
      in south China from 2014 to 2016. Their full genomes were sequenced, compared,
      and analyzed with other reference strains of ALV. The complete genomic nucleotide
      sequences of GD150509, GD160403, GD160607, GDFX0601, and GDFX0602 were 7482 bp in
      length, whereas GDFX0603 was 7480 bp. They shared 99.7% to 99.8% identity with
      each other. Homology analysis showed that the gag, pol, long terminal repeats
      (LTRs), and the transmembrane region (gp37) of the env genes of the 6 viruses
      were well conserved to endogenous counterpart sequences (>97.8%). However, the
      gp85 genes displayed high variability with any known chicken ALV strains. Growth
      kinetics of DF-1 cells infected with the isolated ALV showed viral titers that
      were lower than those infected with the GD13 (ALV-A), CD08 (ALV-B), and CHN06
      (ALV-J) on day 7 post-infection. The infected Specific-pathogen-free (SPF)
      chickens could produce continuous viremia, atrophy of immune organs, growth
      retardation and no tumors were observed. These subgroup ALVs are unique and may
      be common in south China. The results suggested that updating the control and
      eradication program of exogenous ALV for yellow feather broiler breeders in south
      China needs to be considered because of the emergence of the new subgroup
      viruses.

PMID- 29652855
TI  - A New Model for the Dynamics of Hepatitis C Infection: Derivation, Analysis and
      Implications.
AB  - We review various existing models of hepatitis C virus (HCV) infection and show
      that there are inconsistencies between the models and known behaviour of the
      infection. A new model for HCV infection is proposed, based on various dynamical
      processes that occur during the infection that are described in the literature.
      This new model is analysed, and three steady state branches of solutions are
      found when there is no stem cell generation of hepatocytes. Unusually, the branch
      of infected solutions that connects the uninfected branch and the pure infection
      branch can be found analytically and always includes a limit point, subject to a
      few conditions on the parameters. When the action of stem cells is included, the
      bifurcation between the pure infection and infected branches unfolds, leaving a
      single branch of infected solutions. It is shown that this model can generate
      various viral load profiles that have been described in the literature, which is
      confirmed by fitting the model to four viral load datasets. Suggestions for
      possible changes in treatment are made based on the model.

PMID- 29652857
TI  - Indoor Radon Exposure in Italian Schools.
AB  - BACKGROUND: The aim of the study was to assess radon concentration in schoolrooms
      in a city located in the midwest of Italy. METHODS: A two-phase environmental
      study was carried out in 19 school buildings of 16 primary, secondary, and
      tertiary schools. RESULTS: Median (interquartile range-IQR) indoor radon
      concentration in schoolrooms was 91.6 (45.0-140.3) Bq/m3. The highest (median
      952.8 Bq/m3) radon concentration was found in one (3.6%) classroom, located in a
      building of a primary school whose median concentration was 185 Bq/m3. Radon
      concentration was significantly correlated with the number of students and
      teachers, foundation wall construction material, and with the absence of
      underground floors. A geopedological survey was performed close to the building
      with highest radon level, showing the presence of granite and tonalithic
      granodiorite in the soil. CONCLUSIONS: Radon levels should be routinely assessed
      where individuals live or work. Schools are susceptible targets, because of
      childhood stay and the long daily stay of occupants. Low-cost interventions, such
      as implementation of natural air ventilation and school maintenance, can reduce
      radon levels, limiting individual exposure.

PMID- 29652859
TI  - Carbon Emission Reduction with Capital Constraint under Greening Financing and
      Cost Sharing Contract.
AB  - Motivated by the industrial practices, this work explores the carbon emission
      reductions for the manufacturer, while taking into account the capital constraint
      and the cap-and-trade regulation. To alleviate the capital constraint, two
      contracts are analyzed: greening financing and cost sharing. We use the
      Stackelberg game to model four cases as follows: (1) in Case A1, the manufacturer
      has no greening financing and no cost sharing; (2) in Case A2, the manufacturer
      has greening financing, but no cost sharing; (3) in Case B1, the manufacturer has
      no greening financing but has cost sharing; and, (4) in Case B2, the manufacturer
      has greening financing and cost sharing. Then, using the backward induction
      method, we derive and compare the equilibrium decisions and profits of the
      participants in the four cases. We find that the interest rate of green finance
      does not always negatively affect the carbon emission reduction of the
      manufacturer. Meanwhile, the cost sharing from the retailer does not always
      positively affect the carbon emission reduction of the manufacturer. When the
      cost sharing is low, both of the participants' profits in Case B1 (under no
      greening finance) are not less than that in Case B2 (under greening finance).
      When the cost sharing is high, both of the participants' profits in Case B1
      (under no greening finance) are less than that in Case B2 (under greening
      finance).

PMID- 29652858
TI  - Oncosuppressors and Oncogenes: Role in Haemangioma Genesis and Potential for
      Therapeutic Targeting.
AB  - Genetic lesions in proto-oncogenes result in the perturbation of angiogenesis,
      the formation of neovessels from a pre-existing microvasculature. Similarly, the
      subversion of tumor suppressor genes promotes tumor vascularization. Excessive
      neovessel formation is associated with various neoplasms such as infantile
      hemangiomas (IH). Hemangiomas are the most common tumors in pediatric patients
      and at present have no definitive treatment. The pathogenesis of IH is not well
      understood; however, both vasculogenesis and angiogenesis are associated with
      hemangioma genesis. A number of factors that modulate angiogenesis and
      vasculogenesis have been shown to be dysregulated in IH. Several of the oncogenes
      and tumor suppressors linked to the promotion of angiogenesis are also altered in
      infantile hemangioma. In this review, the roles of oncogenes and tumor suppressor
      genes during neovascularization and hemangioma genesis are explored. In addition,
      the potential for targeting these genes in IH therapy is discussed.

PMID- 29652860
TI  - Atomic Force Microscopy Based Tip-Enhanced Raman Spectroscopy in Biology.
AB  - Most biological phenomena occur at the nanometer scale, which is not accessible
      by the conventional optical techniques because of the optical diffraction
      limitation. Tip-enhanced Raman spectroscopy (TERS), one of the burgeoning probing
      techniques, not only can provide the topography characterization with high
      resolution, but also can deliver the chemical or molecular information of a
      sample beyond the optical diffraction limitation. Therefore, it has been widely
      used in various structural analyses pertaining to materials science, tissue
      engineering, biological processes and so on. Based on the different feedback
      mechanisms, TERS can be classified into three types: atomic force microscopy
      based TERS system (AFM-TERS), scanning tunneling microscopy based TERS system
      (STM-TERS) and shear force microscopy based TERS system (SFM-TERS). Among them,
      AFM-TERS is the most widely adopted feedback system by live biosamples because it
      can work in liquid and this allows the investigation of biological molecules
      under native conditions. In this review, we mainly focus on the applications of
      AFM-TERS in three biological systems: nucleic acids, proteins and pathogens. From
      the TERS characterization to the data analysis, this review demonstrates that AFM
      TERS has great potential applications to visually characterizing the biomolecular
      structure and crucially detecting more nano-chemical information of biological
      systems.

PMID- 29652861
TI  - Separate and Combined Response to UV-B Radiation and Jasmonic Acid on
      Photosynthesis and Growth Characteristics of Scutellaria baicalensis.
AB  - The negative effects of enhanced ultraviolet-B (UV-B) on plant growth and
      development have been reported with many species. Considering the ability of
      jasmonic acid (JA) to improve plant stress tolerance, the hypothesis that JA
      pretreatment could alleviate the adverse effects of UV-B on S. baicalensis was
      tested in this study with photosynthesis and growth characteristics. The results
      showed that UV-B or JA alone both induced photosynthesis inhibition and decreased
      biomass in stems and leaves. However, the photosynthetic reduction caused by
      increased UV-B was mainly related to the effect of nonstomatal-limitation, while
      that of JA was a stomatal-limitation effect. JA pretreatment prior to UV-B could
      remit the photosynthetic inhibition via the recovery of chlorophyll content,
      stomatal conductance; and intercellular CO2 concentration (especially the maximum
      electron transport rate increase). Furthermore, the coaction of JA and enhanced
      UV-B alleviated some disadvantageous effects on the leaf and did not aggravate
      the growth damage induced by their separate actions.

PMID- 29652856
TI  - Temperature Effects Explain Continental Scale Distribution of Cyanobacterial
      Toxins.
AB  - Insight into how environmental change determines the production and distribution
      of cyanobacterial toxins is necessary for risk assessment. Management guidelines
      currently focus on hepatotoxins (microcystins). Increasing attention is given to
      other classes, such as neurotoxins (e.g., anatoxin-a) and cytotoxins (e.g.,
      cylindrospermopsin) due to their potency. Most studies examine the relationship
      between individual toxin variants and environmental factors, such as nutrients,
      temperature and light. In summer 2015, we collected samples across Europe to
      investigate the effect of nutrient and temperature gradients on the variability
      of toxin production at a continental scale. Direct and indirect effects of
      temperature were the main drivers of the spatial distribution in the toxins
      produced by the cyanobacterial community, the toxin concentrations and toxin
      quota. Generalized linear models showed that a Toxin Diversity Index (TDI)
      increased with latitude, while it decreased with water stability. Increases in
      TDI were explained through a significant increase in toxin variants such as MC
      YR, anatoxin and cylindrospermopsin, accompanied by a decreasing presence of MC
      LR. While global warming continues, the direct and indirect effects of increased
      lake temperatures will drive changes in the distribution of cyanobacterial toxins
      in Europe, potentially promoting selection of a few highly toxic species or
      strains.

PMID- 29652862
TI  - Inhibitory Effects of Human Primary Intervertebral Disc Cells on Human Primary
      Osteoblasts in a Co-Culture System.
AB  - Spinal fusion is a common surgical procedure to address a range of spinal
      pathologies, like damaged or degenerated discs. After the removal of the
      intervertebral disc (IVD), a structural spacer is positioned followed by internal
      fixation, and fusion of the degenerated segment by natural bone growth. Due to
      their osteoinductive properties, bone morphogenetic proteins (BMP) are applied to
      promote spinal fusion. Although spinal fusion is successful in most patients, the
      rates of non-unions after lumbar spine fusion range from 5% to 35%. Clinical
      observations and recent studies indicate, that the incomplete removal of disc
      tissue might lead to failure of spinal fusion. Yet, it is still unknown if a
      secretion of BMP antagonists in intervertebral disc (IVD) cells could be the
      reason of inhibition in bone formation. In this study, we co-cultured human
      primary osteoblasts (OB) and IVD cells i.e., nucleus pulposus (NPC), annulus
      fibrosus (AFC) and cartilaginous endplate cells (CEPC), to test the possible
      inhibitory effect from IVD cells on OB. Although we could see a trend in lower
      matrix mineralization in OB co-cultured with IVD cells, results of alkaline
      phosphatase (ALP) activity and gene expression of major bone genes were
      inconclusive. However, in NPC, AFC and CEPC beads, an up-regulation of several
      BMP antagonist genes could be detected. Despite being able to show several
      indicators for an inhibition of osteoinductive effects due to IVD cells, the
      reasons for pseudarthrosis after spinal fusion remain unclear.

PMID- 29652863
TI  - Ship Detection from Ocean SAR Image Based on Local Contrast Variance Weighted
      Information Entropy.
AB  - Ship detection from synthetic aperture radar (SAR) images is one of the crucial
      issues in maritime surveillance. However, due to the varying ocean waves and the
      strong echo of the sea surface, it is very difficult to detect ships from
      heterogeneous and strong clutter backgrounds. In this paper, an innovative ship
      detection method is proposed to effectively distinguish the vessels from complex
      backgrounds from a SAR image. First, the input SAR image is pre-screened by the
      maximally-stable extremal region (MSER) method, which can obtain the ship
      candidate regions with low computational complexity. Then, the proposed local
      contrast variance weighted information entropy (LCVWIE) is adopted to evaluate
      the complexity of those candidate regions and the dissimilarity between the
      candidate regions with their neighborhoods. Finally, the LCVWIE values of the
      candidate regions are compared with an adaptive threshold to obtain the final
      detection result. Experimental results based on measured ocean SAR images have
      shown that the proposed method can obtain stable detection performance both in
      strong clutter and heterogeneous backgrounds. Meanwhile, it has a low
      computational complexity compared with some existing detection methods.

PMID- 29652864
TI  - Honey Bee as Alternative Medicine to Treat Eleven Multidrug-Resistant Bacteria
      Causing Urinary Tract Infection during Pregnancy.
AB  - Medicinal benefits of honey bee have been recognized in the medical community
      since ancient times as a remedy for many diseases and infections. This study
      aimed to investigate the in vitro susceptibility of 11 multidrug-resistant
      bacterial strains, isolated from urinary tract infections of pregnant women, to
      six honey samples collected from different localities in the east of Algeria. The
      evaluation of the antibacterial activity was performed by the well method
      followed by the broth dilution method using two-fold dilutions of each honey
      sample ranging from 2.5 to 80% (w/v). The results obtained in this study revealed
      that all tested honeys exhibited potent antibacterial activity against the tested
      strains. The diameters of inhibition ranged from 19.67 to 53.33 mm, with minimum
      inhibitory concentrations (MICs) ranging from 2.5 to 40% (w/v) and minimum
      bactericidal concentration (MBCs) varied between 2.5 and 80% (w/v). Gram-positive
      bacteria were found to be more susceptible than Gram-negative bacteria with
      diameters ranging from 43.33 to 53.33 mm; MIC and MBC values ranged from 2.5 to
      5% (w/v). The P.aeruginosa strain was found to be less susceptible than other
      strains with inhibitory diameters ranging from 19.67 to 27.33 mm; MICs ranged
      from 20 to 40% and MBCs ranged from 20 to 80% (w/v). This contribution has
      provided a broad overview of the antibacterial activity of Algerian honey and
      shown that honey bee has great potential for therapeutic use as an alternative
      therapy for urinary tract infection treatment which is safe and efficient during
      pregnancy.

PMID- 29652866
TI  - Optimizing the Energy and Throughput of a Water-Quality Monitoring System.
AB  - This work presents a new approach to the maximization of energy and throughput in
      a wireless sensor network (WSN), with the intention of applying the approach to
      water-quality monitoring. Water-quality monitoring using WSN technology has
      become an interesting research area. Energy scarcity is a critical issue that
      plagues the widespread deployment of WSN systems. Different power supplies,
      harvesting energy from sustainable sources, have been explored. However, when
      energy-efficient models are not put in place, energy harvesting based WSN systems
      may experience an unstable energy supply, resulting in an interruption in
      communication, and low system throughput. To alleviate these problems, this paper
      presents the joint maximization of the energy harvested by sensor nodes and their
      information-transmission rate using a sum-throughput technique. A wireless
      information and power transfer (WIPT) method is considered by harvesting energy
      from dedicated radio frequency sources. Due to the doubly near-far condition that
      confronts WIPT systems, a new WIPT system is proposed to improve the fairness of
      resource utilization in the network. Numerical simulation results are presented
      to validate the mathematical formulations for the optimization problem, which
      maximize the energy harvested and the overall throughput rate. Defining the
      performance metrics of achievable throughput and fairness in resource sharing,
      the proposed WIPT system outperforms an existing state-of-the-art WIPT system,
      with the comparison based on numerical simulations of both systems. The improved
      energy efficiency of the proposed WIPT system contributes to addressing the
      problem of energy scarcity.

PMID- 29652865
TI  - Calsenilin, a Presenilin Interactor, Regulates RhoA Signaling and Neurite
      Outgrowth.
AB  - Calsenilin modulates A-type potassium channels, regulates presenilin-mediated
      gamma-secretase activity, and represses prodynorphin and c-fos genes expression.
      RhoA is involved in various cellular functions including proliferation,
      differentiation, migration, transcription, and regulation of the actin
      cytoskeleton. Although recent studies demonstrate that calsenilin can directly
      interact with RhoA and that RhoA inactivation is essential for neuritogenesis, it
      is uncertain whether there is a link between calsenilin and RhoA-regulated
      neuritogenesis. Here, we investigated the role of calsenilin in RhoA-regulated
      neuritogenesis using in vitro and in vivo systems. We found that calsenilin
      induced RhoA inactivation, which accompanied RhoA phosphorylation and the reduced
      phosphorylation levels of LIM kinase (LIMK) and cofilin. Interestingly, PC12
      cells overexpressing either full-length (FL) or the caspase 3-derived C-terminal
      fragment (CTF) of calsenilin significantly inactivated RhoA through its
      interaction with RhoA and p190 Rho GTPase-activating protein (p190RhoGAP). In
      addition, cells expressing FL and the CTF of calsenilin had increased neurite
      outgrowth compared to cells expressing the N-terminal fragment (NTF) of
      calsenilin or vector alone. Moreover, Tat-C3 and Y27632 treatment significantly
      increased the percentage of neurite-bearing cells, neurite length, and the number
      of neurites in cells. Finally, calsenilin deficiency in the brains of calsenilin
      knockout mice significantly interfered with RhoA inactivation. These findings
      suggest that calsenilin contributes to neuritogenesis through RhoA inactivation.

PMID- 29652867
TI  - Intercomparison on Four Irrigated Cropland Maps in Mainland China.
AB  - Wide-coverage spatial information on irrigated croplands is a vital foundation
      for food security and water resources studies at the regional level. Several
      global irrigated-cropland maps have been released to the public over the past
      decade due to the efforts of the remote sensing community. However, the
      consistency and discrepancy between these maps is largely unknown because of a
      lack of comparative studies, limiting their use and improvement. To close this
      knowledge gap, we compared the latest four irrigated-cropland datasets (GMIA,
      GRIPC, GlobCover, and GFSAD) in mainland China. First, the four maps were
      compared quantitatively and neutral regional- and provincial-level statistics of
      the relative proportions of irrigated land were obtained through regression
      analysis. Second, we compared the similarities and discrepancies of the datasets
      on spatial grids. Furthermore, the contributions of mosaic cropland pixels in
      GlobCover and GFSAD were also analyzed because of their extensive distribution
      and ambiguous content. Results showed that GMIA has the lowest dispersion and
      best statistical correlation followed by GRIPC, while the corresponding features
      of GlobCover and GFSAD are approximately equal. Spatial agreement of the four
      maps is higher in eastern than western China, and disagreement is contributed
      mostly by GlobCover and GFSAD. However, divergence exists in the ratios of the
      different agreement levels, as well as their sources, on a regional scale. Mosaic
      pixels provide more than half of the irrigated areas for GlobCover and GFSAD, and
      they include both correct and incorrect information. Our results indicate a need
      for a uniform quantitative classification system and for greater focus on
      heterogeneous regions. Furthermore, the results demonstrate the advantage of
      numerical restriction in the calculations. Therefore, special attention should be
      paid to integrating databases and to exploring remote sensing features and
      methods for spatial reconstruction and identification of untypical irrigation
      areas.

PMID- 29652868
TI  - Nature Disaster Risk Evaluation with a Group Decision Making Method Based on
      Incomplete Hesitant Fuzzy Linguistic Preference Relations.
AB  - Because the natural disaster system is a very comprehensive and large system, the
      disaster reduction scheme must rely on risk analysis. Experts' knowledge and
      experiences play a critical role in disaster risk assessment. The hesitant fuzzy
      linguistic preference relation is an effective tool to express experts'
      preference information when comparing pairwise alternatives. Owing to the lack of
      knowledge or a heavy workload, information may be missed in the hesitant fuzzy
      linguistic preference relation. Thus, an incomplete hesitant fuzzy linguistic
      preference relation is constructed. In this paper, we firstly discuss some
      properties of the additive consistent hesitant fuzzy linguistic preference
      relation. Next, the incomplete hesitant fuzzy linguistic preference relation, the
      normalized hesitant fuzzy linguistic preference relation, and the acceptable
      hesitant fuzzy linguistic preference relation are defined. Afterwards, three
      procedures to estimate the missing information are proposed. The first one deals
      with the situation in which there are only n-1 known judgments involving all the
      alternatives; the second one is used to estimate the missing information of the
      hesitant fuzzy linguistic preference relation with more known judgments; while
      the third procedure is used to deal with ignorance situations in which there is
      at least one alternative with totally missing information. Furthermore, an
      algorithm for group decision making with incomplete hesitant fuzzy linguistic
      preference relations is given. Finally, we illustrate our model with a case study
      about flood disaster risk evaluation. A comparative analysis is presented to
      testify the advantage of our method.

PMID- 29652869
TI  - Effect of Sustained Hypoxia on Autophagy of Genioglossus Muscle-Derived Stem
      Cells.
AB  - BACKGROUND Previous studies have demonstrated that sustained hypoxia in people
      with obstructive sleep apnea (OSA) impairs upper airway muscle activity, but the
      underlying mechanism remains poorly understood. As autophagy acts as an important
      regulator under hypoxia stress, we performed an in vitro investigation of the
      effects of sustained hypoxia on autophagy of genioglossus muscle-derived stem
      cells (GG MDSC), an important component of the upper airway muscle. MATERIAL AND
      METHODS Genioglossus MDSCs were obtained from Sprague-Dawley (SD) rats and
      identified by using immunofluorescence staining for CD34, Sca-1, and desmin. GG
      MDSCs were incubated under normoxic or sustained hypoxic conditions for different
      periods of time. Western blotting was used to detect LC3 and Beclin 1, which are
      2 important proteins in autophagy flux, and autophagolysosomes accumulation was
      observed by transmission electron microscopy (TEM). The mRNA and protein levels
      of HIF-1alpha and BNIP3 were evaluated by RT-PCR and Western blot analysis,
      respectively. RESULTS Our study shows that sustained hypoxia promotes the
      expression of LC3BII and Beclin 1 in GG MDSCs in a time-dependent manner. TEM
      showed an increased number of autophagolysosomes in GG MDSCs under sustained
      hypoxia for 12 and 24 h. In addition, hypoxia activated the HIF-1alpha/BNIP3
      signal pathway both at protein levels (shown by Western blot) and at mRNA levels
      (shown by RT-PCR). CONCLUSIONS Our study shows that sustained hypoxia promotes
      autophagy in GG MDSCs, and the HIF-1a/BNIP3 signal pathway was involved in this
      process.

PMID- 29652870
TI  - Surveillance for the identification of cases of acute respiratory infection by
      enterovirus D68 in children in a tertiary level care hospital during 2014-2016.
AB  - Background: The reemergence of enterovirus D68 (EV-D68) infections in the United
      States was reported from August-October 2014 (691 cases). In Mexico, an outbreak
      at the National Institute of Respiratory Diseases was reported (24 cases). The
      results of epidemiological surveillance of Enterovirus sp. (EV) and other
      respiratory viruses in a national pediatric tertiary care level hospital are
      presented. Methods: Following the alert issued by the reemergence of EV-D68 in
      2014, epidemiological surveillance -which only detected respiratory viruses by
      PCR in patients with influenza-like illness using nasopharyngeal swabs- expanded
      to include children with asthma exacerbation or acute respiratory distress.
      Positive samples to EV were confirmed and typed by sequencing. Subsequent
      sequencing was used to obtain the complete viral genome. Results: Of 1705
      samples, 13 were positive to EV. Patients with EV presented the following
      comorbidities: chronic lung disease (7.7%), neoplastic disease (15.4%), allergic
      asthma/rhinitis (23%), recurrent pneumonia (23%), and other (23%). Of the 13
      samples positive for EV, three were positive for EV-D68. These cases required
      invasive mechanical ventilation, presented no neurological involvement and
      survived. Conclusions: The impact of the population studied by EV-D68 was lower
      than that reported in Mexico during the same period. Cases of EV-D68 infection
      had multiple comorbidities, but few pulmonary comorbidities, which could explain
      the low attack rate. The epidemiological surveillance and infection prevention
      system may have contained the outbreak.

PMID- 29652871
TI  - Calcium-creatinine ratio in a morning urine sample for the estimation of
      hypercalciuria associated with non-glomerular hematuria observed in children and
      adolescents.
AB  - Background: Hypercalciuria might be revealed during the differential diagnosis of
      hematuria accompanying renal lithiasis (RL). In spite of this, diagnostic
      accuracy of calcium urinary excretion might be affected by incomplete 24-hour
      urine collections. In the present study, the diagnostic utility of
      calcium/creatinine (ICaCre) index for determining hypercalciuria associated with
      non-glomerular hematuria (NGH) and RL was assessed. Method: ICaCre (mg/mg) index
      was calculated from calcium (mmol/l) and creatinine (umol/l) concentrations in an
      aliquot from a 24-hour urine collection in 169 children and adolescents with NGH
      or RL. Calciuria values > 4.0 mg/kg in 24 hours were distributed according to the
      presence of NGH or RL. Results: Mean ICaCre index was 0.2 +/- 0.1 mg/mg.
      Calciuria values estimated from ICaCre were statistically higher to those from 24
      hour urine collection (p < 0.05). The frequency of hypercalciuria was independent
      from the measurement method (estimated from ICaCre 39.5% vs. 24 h collection
      32.1%; p > 0.05). Hypercalciuria distribution was as follows: no NGH + no RL:
      59.0%; no NGH + RL: 60.0% (? = +1.0%); NGH + no RL: 68.2% (? = +9.2%); NGH + RL:
      73.3% (? = +14.4%). Conclusions: The use of ICaCre index for determining calcium
      urine excretion might be effective in the study of hypercalciuria associated with
      NGH and RL.

PMID- 29652872
TI  - Medical management of transgender children and adolescents.
AB  - Transgender or gender nonconforming (GN) persons identify themselves with a
      gender which is different from that correspondent to their birth sex. The demand
      for health services by families with transgender children or adolescents tends to
      increase. The prevalence of GN in children is unknown; however, it has been
      estimated to be > 1% in adolescents. Transgender persons are at increased risk of
      depression, suicide, illicit drug abuse, human immunodeficiency virus infection,
      and non-accidental injury. The most accepted model for the care of transgender
      persons assumes that these adverse outcomes are the consequence of social
      margination rather than the GI condition itself. Social and physical gender
      transition seem to be effective in increasing the well-being of people with GI
      and reducing associated health risks. Mental health professionals can support the
      child in the process of social transition. The pediatric endocrinologist may
      offer puberty blockade and cross-sex induction of puberty. Surgical sex
      reassignment interventions are reserved for adults. Gender identity, gender
      expression and sexual orientation are three relatively independent categories
      that can take any value, which is not necessarily binary (male/female) or fixed.
      Health professionals should be familiar with these concepts in order to offer the
      best resources available to optimize the well-being of each transgender child or
      adolescent with an individualized approach.

PMID- 29652874
TI  - Evaluation of the Boletin Medico del Hospital Infantil de Mexico by the
      Literature Selection Technical Review Committee of the National Library of
      Medicine.

PMID- 29652875
TI  - Evaluation of recurrence of musculoskeletal tumors with thallium-201 scintigraphy
      plus SPECT/CT in pediatric population.
AB  - Background: Imaging studies, particularly simple and contrast-enhanced
      tomography, constitute the first diagnostic approach to detect recurrence of
      musculoskeletal tumors. The aim of the present retrospective study was to
      demonstrate the usefulness of scintigraphy plus SPECT/CT (single photon emission
      computed tomography) with thallium-201 (201Tl) in the evaluation of malignant
      musculoskeletal tumors with suspicion of recurrence or metastatic disease.
      Methods: Eight weeks after the last therapy, 72 scintigraphy and SPECT/CT studies
      were performed to assess regional recurrence and metastatic disease in 42
      patients with different types of malignant musculoskeletal tumors, such as
      osteosarcoma, Ewing's sarcoma, rhabdomyosarcoma, retinoblastoma, synovial
      sarcoma, and Wilms tumor at the Hospital Infantil de Mexico Federico Gomez. The
      positive predictive value (PPV) and the confidence interval of the scintigraphy
      and SPECT/CT were calculated when compared with the results of the
      histopathological analysis and the clinical and radiological follow-up for the
      identification of recurrence. Results: Scintigraphy was abnormal in 30 (71.4%) of
      the 42 patients; 33 lesions (30 patients) were detected by scintigraphy and 25
      lesions (21 patients) by chest X-ray and tomography of two regions. The SPECT/CT
      was performed on 30 patients, where 12 lesions were detected in addition to the
      planar scintigraphy. Scintigraphy showed a PPV of 82%; SPECT/CT, 100%.
      Conclusion: 201Tl-scintigraphy can be considered as an adequate study to identify
      the sites of tumor viability with a high degree of diagnostic certainty combined
      with the SPECT/CT technique.

PMID- 29652876
TI  - Rehabilitation of sucking and swallowing alterations in premature newborn at the
      neonatal intensive care unit.
AB  - Over the last 20 years, 640 premature newborns with alterations in suction
      deglution have been taken care of in the neonatal intensive care unit at the
      Hospital Infantil de Mexico Federico Gomez, using techniques for patients with
      immaturity, and neurological, gastrointestinal, cardiologic and respiratory
      pathologies. This descriptive study includes the treatment employed mainly in
      premature newborns during this period. Suction, swallowing and breathing
      coordination are some of the most complex abilities that premature newborns face,
      due to their anatomofunctional immaturity and improper sensoriomotor integration
      for the high energy requirements they must meet. Sucking and swallowing are
      voluntary and involuntary processes that guarantee the safe passage of food from
      mouth to stomach, and require the coordination of the cranial nerves, the brain
      stem and cerebral cortex and muscles of the mouth, pharynx and esophagus. The
      rehabilitation treatment consists in the positioning of the newborn and
      caretaker, adaptation of teat, regulation of muscle tone and progressive intake
      of milk. The feeding processing was reduced to 1.5 weeks in newborns submitted to
      treatment, whereas in those who did not receive the treatment, the proccess took
      up to 3 weeks.

PMID- 29652877
TI  - Oscar Miguel Aguirre Jauregui (1939-2017).

PMID- 29652878
TI  - Prevalence of exclusive breastfeeding in the healthy newborn.
AB  - Background: The best nourishment for infants during the first 6 months of life is
      exclusive breastfeeding. It is recommended along with other food to complement
      the diet until the child is 2 years old, as long as the mother and the child are
      willing to continue with it. The objectives of this study were to determine he
      exclusive breastfeeding rate in full term newborns at hospital discharge and 15
      days later and to analyze the factors that positively affect the exclusive
      breastfeeding. Methods: A prospective study was conducted in which a sample of
      postpartum women with full term newborns was recruited during hospital admission.
      Different variables were compiled and two interviews were made to determine the
      kind of feeding they were giving their children and if it was maintained at 15
      days of birth. Results: Exclusive breastfeeding rate at hospital discharge is
      much lower than recommended. It significantly decreases at 15 days of birth,
      increasing artificial feeding. It seems that having a vaginal birth, no
      complications giving birth, providing early breastfeeding and skin-to-skin
      contact in the delivery room are predisposing factors necessary to establish a
      good breastfeeding at hospital discharge. Conclusions: Despite the efforts of
      professionals, the percentage of newborns with exclusive breastfeeding at birth
      is not enough for the current recommendations.

PMID- 29652879
TI  - Biobeam-Multiplexed wave-optical simulations of light-sheet microscopy.
AB  - Sample-induced image-degradation remains an intricate wave-optical problem in
      light-sheet microscopy. Here we present biobeam, an open-source software package
      that enables simulation of operational light-sheet microscopes by combining data
      from 105-106 multiplexed and GPU-accelerated point-spread-function calculations.
      The wave-optical nature of these simulations leads to the faithful reproduction
      of spatially varying aberrations, diffraction artifacts, geometric image
      distortions, adaptive optics, and emergent wave-optical phenomena, and renders
      image-formation in light-sheet microscopy computationally tractable.

PMID- 29652880
TI  - Correction: PLOS Neglected Tropical Diseases 2017 Reviewer and Editorial Board
      Thank You.
AB  - [This corrects the article DOI: 10.1371/journal.pntd.0006359.].

PMID- 29652881
TI  - The simultaneous assessment of glycosylated hemoglobin, fasting plasma glucose
      and oral glucose tolerance test does not improve the detection of type 2 diabetes
      mellitus in Colombian adults.
AB  - INTRODUCTION: Guidelines recommend early detection of type 2 diabetes mellitus
      (DM2). The objective of the present study was to evaluate the capacity to
      identify DM2 in subjects that were screened for DM2 simultaneously with all three
      of the tests recommended-fasting plasma glucose (FPG), glycosylated hemoglobin
      (HbA1c) and a 2-hour post 75-g oral glucose tolerance test (OGTT). METHODS AND
      RESULTS: The present analysis of an anonymous database of 1113 adults from a
      reference clinical laboratory in Bucaramanga, Colombia, was an observational,
      descriptive, cross-sectional secondary source study. 259 individuals met at least
      one of the criteria for DM2: FPG >= 126mg/dL (7.0mmol/L), HbA1c >= 6.5%
      (48mmol/mol) and OGTT >= 200mg/dL (11.1mmol/L). 30 subjects (2.7%) were diabetic
      according to FPG, 56 subjects (5.0%) by HbA1c and 250 subjects (22.5%) by OGTT.
      In total 259 subjects (23.3% [IC 95%: 20.7%- 25.8%] were diabetic either by FPG,
      OGTT or HbA1c. DISCUSSION: The largest number of patients were identified as
      diabetic with the OGTT. The combination of two or three tests did not increase
      the detection of new cases of DM2. Our findings suggest that routinely requesting
      FPG, OGTT and HbA1c at the same time may be inappropriate in at risk individuals,
      as this approach does not significantly improve the diagnostic capacity compared
      to using FPG+OGTT and substantially increases the financial burden on the health
      system, insurers or individual.

PMID- 29652882
TI  - Association between supplementary private health insurance and visits to
      physician offices versus hospital outpatient departments among adults with
      diabetes in the universal public insurance system.
AB  - BACKGROUND: Diabetes mellitus is a chronic disease with a high prevalence across
      the world as well as in South Korea. Most cases of diabetes can be adequately
      managed at physician offices, but many diabetes patients receive outpatient care
      at hospitals. This study examines the relationship between supplementary private
      health insurance (SPHI) ownership and the use of hospitals among diabetes
      outpatients within the universal public health insurance scheme. METHODS: Data
      from the 2011 Korea Health Panel, a nationally representative sample of Korean
      individuals, was used. For the study, 6,379 visits for diabetes care were
      selected while controlling for clustered errors. Multiple logistic regression
      models were used to examine determinants of hospital outpatient services.
      RESULTS: This study demonstrated that the variables of self-rated health status,
      comorbidity, unmet need, and alcohol consumption significantly correlated with
      the choice to use a hospital services. Patients with SPHI were more likely to use
      medical services at hospitals by 1.71 times (95% CI 1.068-2.740, P = 0.026)
      compared to patients without SPHI. CONCLUSIONS: It was confirmed that diabetic
      patients insured by SPHI had more use of hospital services than those who were
      not insured. People insured by SPHI seem to be more likely to use hospital
      services because SPHI lightens the economic burden of care.

PMID- 29652883
TI  - Correction: GOST: A generic ordinal sequential trial design for a treatment trial
      in an emerging pandemic.
AB  - [This corrects the article DOI: 10.1371/journal.pntd.0005439.].

PMID- 29652884
TI  - Neochloris oleoabundans is worth its salt: Transcriptomic analysis under salt and
      nitrogen stress.
AB  - Neochloris oleoabundans is an oleaginous microalgal species that can be
      cultivated in fresh water as well as salt water. Using salt water gives the
      opportunity to reduce production costs and the fresh water footprint for large
      scale cultivation. Production of triacylglycerols (TAG) usually includes a
      biomass growth phase in nitrogen-replete conditions followed by a TAG
      accumulation phase under nitrogen-deplete conditions. This is the first report
      that provides insight in the saline resistance mechanism of a fresh water
      oleaginous microalgae. To better understand the osmoregulatory mechanism of N.
      oleoabundans during growth and TAG accumulating conditions, the transcriptome was
      sequenced under four different conditions: fresh water nitrogen-replete and 
      deplete conditions, and salt water (525 mM dissolved salts, 448mM extra NaCl)
      nitrogen-replete and -deplete conditions. In this study, several pathways are
      identified to be responsible for salt water adaptation of N. oleoabundans under
      both nitrogen-replete and -deplete conditions. Proline and the ascorbate
      glutathione cycle seem to be of importance for successful osmoregulation in N.
      oleoabundans. Genes involved in Proline biosynthesis were found to be upregulated
      in salt water. This was supported by Nuclear magnetic resonance (NMR)
      spectroscopy, which indicated an increase in proline content in the salt water
      nitrogen-replete condition. Additionally, the lipid accumulation pathway was
      studied to gain insight in the gene regulation in the first 24 hours after
      nitrogen was depleted. Oil accumulation is increased under nitrogen-deplete
      conditions in a comparable way in both fresh and salt water. The mechanism behind
      the biosynthesis of compatible osmolytes can be used to improve N. oleoabundans
      and other industrially relevant microalgal strains to create a more robust and
      sustainable production platform for microalgae derived products in the future.

PMID- 29652885
TI  - Phosphorelay through the bifunctional phosphotransferase PhyT controls the
      general stress response in an alphaproteobacterium.
AB  - Two-component systems constitute phosphotransfer signaling pathways and enable
      adaptation to environmental changes, an essential feature for bacterial survival.
      The general stress response (GSR) in the plant-protecting alphaproteobacterium
      Sphingomonas melonis Fr1 involves a two-component system consisting of multiple
      stress-sensing histidine kinases (Paks) and the response regulator PhyR; PhyR in
      turn regulates the alternative sigma factor EcfG, which controls expression of
      the GSR regulon. While Paks had been shown to phosphorylate PhyR in vitro, it
      remained unclear if and under which conditions direct phosphorylation happens in
      the cell, as Paks also phosphorylate the single domain response regulator SdrG,
      an essential yet enigmatic component of the GSR signaling pathway. Here, we
      analyze the role of SdrG and investigate an alternative function of the membrane
      bound PhyP (here re-designated PhyT), previously assumed to act as a PhyR
      phosphatase. In vitro assays show that PhyT transfers a phosphoryl group from
      SdrG to PhyR via phosphoryl transfer on a conserved His residue. This finding, as
      well as complementary GSR reporter assays, indicate the participation of SdrG and
      PhyT in a Pak-SdrG-PhyT-PhyR phosphorelay. Furthermore, we demonstrate complex
      formation between PhyT and PhyR. This finding is substantiated by PhyT-dependent
      membrane association of PhyR in unstressed cells, while the response regulator is
      released from the membrane upon stress induction. Our data support a model in
      which PhyT sequesters PhyR, thereby favoring Pak-dependent phosphorylation of
      SdrG. In addition, PhyT assumes the role of the SdrG-phosphotransferase to
      activate PhyR. Our results place SdrG into the GSR signaling cascade and uncover
      a dual role of PhyT in the GSR.

PMID- 29652886
TI  - Simulations of camera-based single-molecule fluorescence experiments.
AB  - Single-molecule microscopy has become a widely used technique in (bio)physics and
      (bio)chemistry. A popular implementation is single-molecule Forster Resonance
      Energy Transfer (smFRET), for which total internal reflection fluorescence
      microscopy is frequently combined with camera-based detection of surface
      immobilized molecules. Camera-based smFRET experiments generate large and complex
      datasets and several methods for video processing and analysis have been
      reported. As these algorithms often address similar aspects in video analysis,
      there is a growing need for standardized comparison. Here, we present a Matlab
      based software (MASH-FRET) that allows for the simulation of camera-based smFRET
      videos, yielding standardized data sets suitable for benchmarking video
      processing algorithms. The software permits to vary parameters that are relevant
      in cameras-based smFRET, such as video quality, and the properties of the system
      under study. Experimental noise is modeled taking into account photon statistics
      and camera noise. Finally, we survey how video test sets should be designed to
      evaluate currently available data analysis strategies in camera-based sm
      fluorescence experiments. We complement our study by pre-optimizing and
      evaluating spot detection algorithms using our simulated video test sets.

PMID- 29652887
TI  - Ethnicity matching and outcomes after kidney transplantation in the United
      Kingdom.
AB  - BACKGROUND: Kidneys from non-white donors have inferior outcomes, but it is
      unclear if ethnicity matching between donors and recipients achieves better post
      kidney transplant outcomes. METHODS: We undertook a retrospective, population
      cohort study utilising UK Transplant Registry data. The cohort comprised adult,
      kidney-alone, transplant recipients receiving their first kidney transplant
      between 2003-2015, with data censored at 1st October 2016. We included 27,970
      recipients stratified into white (n = 23,215), black (n = 1,679) and south Asian
      (n = 3,076) ethnicity, with median post-transplant follow-up of 1,676 days (IQR
      716-2,869 days). Unadjusted and adjusted Cox regression survival analyses were
      performed to investigate ethnicity effect on risk for graft loss and mortality.
      RESULTS: In unadjusted analyses, matched ethnicity between donors-recipients
      resulted in better outcomes for delayed graft function, one-year creatinine,
      graft and patient survival but these differed by ethnicity matches. Compared to
      white-to-white transplants, risk for death-censored graft loss was higher in
      black-to-black and similar among Asian-to-Asian transplants, but mortality risk
      was lower for both black-to-black and Asian-to-Asian transplants. In Cox
      regression models, compared to white donors, we observed higher risk for graft
      loss with both south Asian (HR 1.38, 95%CI 1.12-1.70, p = 0.003) and black (HR
      1.66, 95%CI 1.30-2.11, p<0.001) donated kidneys independent of recipient
      ethnicity. We observed no mortality difference with south Asian donated kidneys
      but increased mortality with black donated kidneys (HR 1.68, 95%CI 1.21-2.35, p =
      0.002). Matching ethnicities made no significant difference in any Cox regression
      model. Similar results were observed after stratifying our analysis by living and
      deceased-donor kidney transplantation. CONCLUSIONS: Our data confirm inferior
      outcomes associated with non-white kidney donors for kidney transplant recipients
      of any ethnicity in a risk-adjusted model for the United Kingdom population.
      However, contrary to non-renal transplant literature, we did not identify any
      survival benefits associated with donor-recipient ethnicity matching.

PMID- 29652888
TI  - Sialome diversity of ticks revealed by RNAseq of single tick salivary glands.
AB  - Ticks salivate while feeding on their hosts. Saliva helps blood feeding through
      host anti-hemostatic and immunomodulatory components. Previous transcriptomic and
      proteomic studies revealed the complexity of tick saliva, comprising hundreds of
      polypeptides grouped in several multi-genic families such as lipocalins, Kunitz
      domain containing peptides, metalloproteases, basic tail secreted proteins, and
      several other families uniquely found in ticks. These studies also revealed that
      the composition of saliva changes with time; expression of transcripts from the
      same family wax and wane as a function of feeding time. Here, we examined whether
      host immune factors could influence sialome switching by comparing sialomes of
      ticks fed naturally on a rabbit, to ticks artificially fed on defibrinated blood
      depleted of immune components. Previous studies were based on transcriptomes
      derived from pools of several individuals. To get an insight into the uniqueness
      of tick sialomes, we performed transcriptomic analyses of single salivary glands
      dissected from individual adult female I. ricinus ticks. Multivariate analysis
      identified 1,279 contigs differentially expressed as a function of time and/or
      feeding mode. Cluster analysis of these contigs revealed nine clusters of
      differentially expressed genes, four of which appeared consistently across
      several replicates, but five clusters were idiosyncratic, pointing to the
      uniqueness of sialomes in individual ticks. The disclosure of tick quantum
      sialomes reveals the unique salivary composition produced by individual ticks as
      they switch their sialomes throughout the blood meal, a possible mechanism of
      immune evasion.

PMID- 29652889
TI  - The rostromedial tegmental nucleus is essential for non-rapid eye movement sleep.
AB  - The rostromedial tegmental nucleus (RMTg), also called the GABAergic tail of the
      ventral tegmental area, projects to the midbrain dopaminergic system, dorsal
      raphe nucleus, locus coeruleus, and other regions. Whether the RMTg is involved
      in sleep-wake regulation is unknown. In the present study, pharmacogenetic
      activation of rat RMTg neurons promoted non-rapid eye movement (NREM) sleep with
      increased slow-wave activity (SWA). Conversely, rats after neurotoxic lesions of
      8 or 16 days showed decreased NREM sleep with reduced SWA at lights on. The
      reduced SWA persisted at least 25 days after lesions. Similarly, pharmacological
      and pharmacogenetic inactivation of rat RMTg neurons decreased NREM sleep.
      Electrophysiological experiments combined with optogenetics showed a direct
      inhibitory connection between the terminals of RMTg neurons and midbrain
      dopaminergic neurons. The bidirectional effects of the RMTg on the sleep-wake
      cycle were mimicked by the modulation of ventral tegmental area (VTA)/substantia
      nigra compacta (SNc) dopaminergic neuronal activity using a pharmacogenetic
      approach. Furthermore, during the 2-hour recovery period following 6-hour sleep
      deprivation, the amount of NREM sleep in both the lesion and control rats was
      significantly increased compared with baseline levels; however, only the control
      rats showed a significant increase in SWA compared with baseline levels.
      Collectively, our findings reveal an essential role of the RMTg in the promotion
      of NREM sleep and homeostatic regulation.

PMID- 29652890
TI  - State tobacco control expenditures and tax paid cigarette sales.
AB  - This research is the first nationally representative study to examine the
      relationship between actual state-level tobacco control spending in each of the 5
      CDC's Best Practices for Comprehensive Tobacco Control Program categories and
      cigarette sales. We employed several alternative two-way fixed-effects regression
      techniques to estimate the determinants of cigarette sales in the United States
      for the years 2008-2012. State spending on tobacco control was found to have a
      negative and significant impact on cigarette sales in all models that were
      estimated. Spending in the areas of cessation interventions, health communication
      interventions, and state and community interventions were found to have a
      negative impact on cigarette sales in all models that were estimated, whereas
      spending in the areas of surveillance and evaluation, and administration and
      management were found to have negative effects on cigarette sales in only some
      models. Our models predict that states that spend up to seven times their current
      levels could still see significant reductions in cigarette sales. The findings
      from this research could help inform further investments in state tobacco control
      programs.

PMID- 29652892
TI  - The effects of electrical field spatial spread and some cognitive factors on
      speech-in-noise performance of individual cochlear implant users-A computer model
      study.
AB  - The relation of the individual speech-in-noise performance differences in
      cochlear implant (CI) users to underlying physiological factors is currently
      poorly understood. This study approached this research question by a step-wise
      individualization of a computer model of speech intelligibility mimicking the
      details of CI signal processing and some details of the physiology present in CI
      users. Two factors, the electrical field spatial spread and internal noise (as a
      coarse model of the individual cognitive performance) were incorporated. Internal
      representations of speech-in-noise mixtures calculated by the model were
      classified using an automatic speech recognizer backend employing Hidden Markov
      Models with a Gaussian probability distribution. One-dimensional electric field
      spatial spread functions were inferred from electrical field imaging data of 14
      CI users. Simplified assumptions of homogenously distributed auditory nerve
      fibers along the cochlear array and equal distance between electrode array and
      nerve tissue were assumed in the model. Internal noise, whose standard deviation
      was adjusted based on either anamnesis data, or text-reception-threshold data, or
      a combination thereof, was applied to the internal representations before
      classification. A systematic model evaluation showed that predicted speech
      reception-thresholds (SRTs) in stationary noise improved (decreased) with
      decreasing internal noise standard deviation and with narrower electric field
      spatial spreads. The model version that was individualized to actual listeners
      using internal noise alone (containing average spatial spread) showed significant
      correlations to measured SRTs, reflecting the high correlation of the text
      reception threshold data with SRTs. However, neither individualization to spatial
      spread functions alone, nor a combined individualization based on spatial spread
      functions and internal noise standard deviation did produce significant
      correlations with measured SRTs.

PMID- 29652891
TI  - Conditional equivalence testing: An alternative remedy for publication bias.
AB  - We introduce a publication policy that incorporates "conditional equivalence
      testing" (CET), a two-stage testing scheme in which standard NHST is followed
      conditionally by testing for equivalence. The idea of CET is carefully considered
      as it has the potential to address recent concerns about reproducibility and the
      limited publication of null results. In this paper we detail the implementation
      of CET, investigate similarities with a Bayesian testing scheme, and outline the
      basis for how a scientific journal could proceed to reduce publication bias while
      remaining relevant.

PMID- 29652893
TI  - Glucose sensor-augmented continuous subcutaneous insulin infusion in patients
      with diabetic gastroparesis: An open-label pilot prospective study.
AB  - Erratic blood glucose levels can be a cause and consequence of delayed gastric
      emptying in patients with diabetes. It is unknown if better glycemic control
      increases risks of hypoglycemia or improves hemoglobin A1c levels and
      gastrointestinal symptoms in diabetic gastroparesis. This study investigated the
      safety and potential efficacy of continuous subcutaneous insulin infusion (CSII)
      and continuous glucose monitoring (CGM) in poorly controlled diabetes with
      gastroparesis. Forty-five type 1 or 2 patients with diabetes and gastroparesis
      and hemoglobin A1c >8% from the NIDDK Gastroparesis Consortium enrolled in a 24
      week open-label pilot prospective study of CSII plus CGM. The primary safety
      outcome was combined numbers of mild, moderate, and severe hypoglycemic events at
      screening and 24 weeks treatment. Secondary outcomes included glycemic excursions
      on CGM, hemoglobin A1c, gastroparesis symptoms, quality-of-life, and liquid meal
      tolerance. Combined mild, moderate, and severe hypoglycemic events occurred
      similarly during the screening/run-in (1.9/week) versus treatment (2.2/week)
      phases with a relative risk of 1.18 (95% CI 0.85-1.64, P = 0.33). CGM time in
      hypoglycemia (<70 mg/dL) decreased from 3.9% to 1.8% (P<0.0001), time in
      euglycemia (70-180 mg/dL) increased from 44.0% to 52.0% (P = 0.02), time in
      severe hyperglycemia (>300 mg/dL) decreased from 14.2% to 7.0% (P = 0.005), and
      hemoglobin A1c decreased from 9.4+/-1.4% to 8.3+/-1.3% (P = 0.001) on CSII plus
      CGM. Symptom scores decreased from 29.3+/-7.1 to 21.9+/-10.2 with lower
      nausea/vomiting, fullness/early satiety, and bloating/distention scores
      (P<=0.001). Quality-of-life scores improved from 2.4+/-1.1 to 3.1+/-1.1
      (P<0.0001) and volumes of liquid nutrient meals tolerated increased from 420+/
      258 to 487+/-312 mL (P = 0.05) at 24 weeks. In conclusion, CSII plus CGM appeared
      to be safe with minimal risks of hypoglycemic events and associated improvements
      in glycemic control, gastroparesis symptoms, quality-of-life, and meal tolerance
      in patients with poorly controlled diabetes and gastroparesis. This study
      supports the safety, feasibility, and potential benefits of improving glycemic
      control in diabetic gastroparesis.

PMID- 29652895
TI  - Complications after transcatheter aortic valve implantation using transfemoral
      and transapical approach in general anaesthesia.
AB  - BACKGROUND: Transcatheter aortic valve implantation (TAVI) is a minimally
      invasive procedure used to treat degenerative heart valve disease. The
      implantation requires a highly specific and interdisciplinary management
      approach. Currently, TAVI is performed with the patient under local or general
      anaesthesia. METHODS: This study was a retrospective analysis of all TAVI
      procedures performed at the University Hospital of Regensburg between January
      2009 and July 2015. All pre-, intra and postoperative data focusing on
      perioperative complications were recorded. RESULTS: A total of 853 transfemoral-
      and transapical-TAVI patients were included in the study. All patients underwent
      general anaesthesia. The ASA classifications were primarily 3-4. The average
      logistic EuroScores for the transfemoral- and transapical-TAVI patients were 18
      +/- 12% and 21 +/- 15% (p = 0.002), respectively. The anaesthesia coverage time
      was 170 +/- 49 min., including 37 +/- 12 minutes for anaesthetic management.
      Overall, 458 complications were recorded; with pneumonia, acute renal failure,
      indication for a permanent pacemaker and non-extubation in the operating theatre
      the most frequently recorded complications. CONCLUSION: In the present study, we
      showed that our patients' outcomes are comparable to those reported in the
      available literature. Compared to TF, TA patients show an overall worse physical
      condition as well as a higher perioperative morbidity and mortality. Consequently
      TA patients need additional care and should only be operated in appropriately
      experienced medical centres.

PMID- 29652894
TI  - Piperazinyl fragment improves anticancer activity of Triapine.
AB  - A new class of TSCs containing piperazine (piperazinylogs) of Triapine, was
      designed to fulfill the di-substitution pattern at the TSCs N4 position, which is
      a crucial prerequisite for the high activity of the previously obtained TSC
      compounds-DpC and Dp44mT. We tested the important physicochemical characteristics
      of the novel compounds L1-L12. The studied ligands are neutral at physiological
      pH, which allows them to permeate cell membranes and bind cellular Fe pools more
      readily than less lipid-soluble ligands, e.g. DFO. The selectivity and anti
      cancer activity of the novel TSCs were examined in a variety of cancer cell
      types. In general, the novel compounds demonstrated the greatest promise as anti
      cancer agents with both a potent and selective anti-proliferative activity. We
      investigated the mechanism of action more deeply, and revealed that studied
      compounds inhibit the cell cycle (G1/S phase). Additionally we detected
      apoptosis, which is dependent on cell line's specific genetic profile.
      Accordingly, structure-activity relationship studies suggest that the combination
      of the piperazine ring with Triapine allows potent and selective anticancer
      chelators that warrant further in vivo examination to be identified.
      Significantly, this study proved the importance of the di-substitution pattern of
      the amine N4 function.

PMID- 29652896
TI  - A cohort study of the effects of older adult care dependence upon household
      economic functioning, in Peru, Mexico and China.
AB  - BACKGROUND: While links between disability and poverty are well established,
      there have been few longitudinal studies to clarify direction of causality,
      particularly among older adults in low and middle income countries. We aimed to
      study the effect of care dependence among older adult residents on the economic
      functioning of their households, in catchment area survey sites in Peru, Mexico
      and China. METHODS: Households were classified from the evolution of the needs
      for care of older residents, over two previous community surveys, as 'incident
      care', 'chronic care' or 'no care', and followed up three years later to
      ascertain economic outcomes (household income, consumption, economic strain,
      satisfaction with economic circumstances, healthcare expenditure and residents
      giving up work or education to care). RESULTS: Household income did not differ
      between household groups. However, income from paid work (Pooled Count Ratio pCR
      0.88, 95% CI 0.78-1.00) and government transfers (pCR 0.80, 95% CI 0.69-0.93)
      were lower in care households. Consumption was 12% lower in chronic care
      households (pCR 0.88, 95% CI 0.77-0.99). Household healthcare expenditure was
      higher (pCR 1.55, 95% CI 1.26-1.90), and catastrophic healthcare spending more
      common (pRR 1.64, 95% CI 1.64-2.22) in care households. CONCLUSIONS: While
      endogeneity cannot be confidently excluded as an explanation for the findings,
      this study indicates that older people's needs for care have a discernable impact
      on household economics, controlling for baseline indicators of long-term economic
      status. Although living, typically, in multigenerational family units, older
      people have not featured prominently in global health and development agendas.
      Population ageing will rapidly increase the number of households where older
      people live, and their societal significance. Building sustainable long-term care
      systems for the future will require some combination of improved income security
      in old age; incentivisation of informal care through compensation for direct and
      opportunity costs; and development of community care services to support, and,
      where necessary, supplement or substitute the central role of informal
      caregivers.

PMID- 29652897
TI  - Oxidative stress and antioxidant defense responses in Acartia copepods in
      relation to environmental factors.
AB  - On a daily basis, planktonic organisms migrate vertically and thus experience
      widely varying conditions in their physico-chemical environment. In the Gulf of
      Finland, these changes are larger than values predicted by climate change
      scenarios predicted for the next century (up to 0.5 units in pH and 5 degrees C
      in temperature). In this work, we are interested in how temporal variations in
      physico-chemical characteristics of the water column on a daily and weekly scale
      influence oxidative stress level and antioxidant responses in the planktonic
      copepod of the genus Acartia. Responses were determined from samples collected
      during a two-week field survey in the western Gulf of Finland, Baltic Sea. Our
      results showed that GST (Glutathione-S-transferase) enzyme activity increased in
      the surface waters between Weeks I and II, indicating antioxidant defense
      mechanism activation. This is most likely due to elevating temperature, pH, and
      dissolved oxygen observed between these two weeks. During Week II also GSSG
      (oxidized glutathione) was detected, indicating that copepods responded to
      stressor(s) in the environment. Our results suggest that Acartia copepods seem
      fairly tolerant to weekly fluctuations in environmental conditions in coastal and
      estuarine areas, in terms of antioxidant defense and oxidative stress. This could
      be directly connected to a very efficient glutathione cycling system acting as
      antioxidant defense system for neutralizing ROS and avoiding elevated levels of
      LPX.

PMID- 29652898
TI  - Tooth loss and pneumonia mortality: A cohort study of Japanese dentists.
AB  - Although associations between oral health and pneumonia have been reported in
      previous studies, particularly in the institutionalized elderly, few prospective
      studies have investigated the association between oral condition and pneumonia
      among community-dwelling people and whether the findings among inpatients or
      patients in nursing homes are applicable to the general population is still
      unclear. The oral bacteria propagated in the periodontal regions may drop into
      the lung and increase the risk of pneumonia. We, therefore, investigated the
      association of tooth loss with mortality from pneumonia in a cohort study of
      Japanese dentists. Members of the Japan Dental Association (JDA) participated in
      the LEMONADE (Longitudinal Evaluation of Multi-phasic, Odontological and
      Nutritional Associations in Dentists) Study. From 2001 to 2006, they completed a
      baseline questionnaire on lifestyle and health factors including the number of
      teeth lost (excluding third molars). We followed 19,775 participants (mean age +/
      standard deviation, 51.4 +/- 11.7 years; 1,573 women [8.0%] and 18,202 men
      [92.0%]) for mortality from pneumonia (ICD-10, J12-J18). Mortality data were
      collected via the fraternal insurance program of the JDA. The hazard ratios (HRs)
      were estimated with adjustment for sex, age, body mass index, smoking status,
      physical activity and diabetes history. During the median follow-up period of 9.5
      years, we documented 68 deaths from pneumonia. Participants who were edentulous
      at baseline were at significantly increased risk of mortality from pneumonia. The
      multivariable-adjusted HRs were 2.07 (95% confidence interval [CI], 1.09-3.95)
      for the edentulous and 1.60 (95% CI, 0.83-3.10) for loss of 15-27 teeth relative
      to loss of 0-14 teeth (trend p = 0.026). The HR per one tooth loss was also
      significant; 1.031 (95% CI, 1.004-1.060). In conclusion, a large number of teeth
      lost may indicate an increased risk of mortality from pneumonia in community
      dwelling populations.

PMID- 29652899
TI  - Self-care for common colds: A European multicenter survey on the role of
      subjective discomfort and knowledge about the self-limited course - The COCO
      study.
AB  - INTRODUCTION: Common colds are the most frequently encountered disease worldwide
      and the most frequent reason for self-care. According to the cross-sectional
      European Common Colds study (COCO), patients use as many as 12 items on average
      for self-care. Little is known about the influence of discomfort and knowledge on
      self-care for common colds. MAIN OBJECTIVE: To understand the influence of
      patients' discomfort during a cold and their knowledge about the self-limited
      disease course on the use of self-care measures. MATERIALS AND METHODS: This COCO
      analysis included 2,204 patients from 22 European primary care sites in 12
      countries. Each site surveyed 120 consecutive adults with a 27-item questionnaire
      asking about patients' self-care, subjective discomfort during a cold
      (discomfort: yes/no), and knowledge about the self-limited course (yes/no).
      Country-specific medians of the number of self-care items served as a cut-off to
      define high and low self-care use. Four groups were stratified based on
      discomfort (yes/no) and knowledge (yes/no). RESULTS: Participants' mean age was
      46.5 years, 61.7% were female; 36.3% lacked knowledge; 70.6% reported discomfort.
      The group has discomfort/no knowledge exhibited the highest mean item use (13.3),
      followed by has discomfort/has knowledge (11.9), no discomfort/no knowledge
      (11.1), and no discomfort/has knowledge (8.8). High use was associated with
      discomfort (OR 1.8; CI 1.5-2.2), female gender (OR 1.7; 1.4-2.0), chronic
      pain/arthritis (OR 1.6; 1.2-2.1), more years of education (OR 1.3; 1.1-1.6), age
      <48 years (OR 1.3; 1.0-1.5), and lack of knowledge (OR 1.2; 1.0-1.4). DISCUSSION:
      Counseling on common colds should address patients' discomfort and soothing
      measures in addition to providing information on the natural disease course.

PMID- 29652900
TI  - Galpha-cAMP/PKA pathway positively regulates pigmentation, chaetoglobosin A
      biosynthesis and sexual development in Chaetomium globosum.
AB  - Sensing the environmental signals, the canonical Galpha-cAMP/PKA pathway
      modulates mycelial growth and development, and negatively regulates some
      secondary metabolism in filamentous fungi, e.g. aflatoxin in Aspergillus
      nidulans. Here we report the characterization of this signaling pathway in
      Chaetomium globosum, a widely spread fungus known for synthesizing abundant
      secondary metabolites, e.g. chaetoglobosin A (ChA). RNAi-mediated knockdown of a
      putative Galpha-encoding gene gna-1, led to plural changes in phenotype, e.g.
      albino mycelium, significant restriction on perithecium development and decreased
      production of ChA. RNA-seq profiling and qRT-PCR verified significantly fall in
      expression of corresponding genes, e.g. pks-1 and CgcheA. These defects could be
      restored by simultaneous knock-down of the pkaR gene encoding a regulatory
      subunit of cAMP-dependent protein kinase A (PKA), suggesting that pkaR had a
      negative effect on the above mentioned traits. Confirmatively, the intracellular
      level of cAMP in wild-type strain was about 3.4-fold to that in gna-1 silenced
      mutant pG14, and addition of a cAMP analog, 8-Br-cAMP, restored the same defects,
      e.g., the expression of CgcheA. Furthermore, the intracellular cAMP in gna-1 and
      pkaR double silenced mutant was approaching the normal level. The following
      activity inhibition experiment proved that the expression of CgcheA was indeed
      regulated by PKA. Down-regulation of LaeA/VeA/SptJ expression in gna-1 mutant was
      also observed, implying that Galpha signaling may crosstalk to other regulatory
      pathways. Taken together, this study proposes that the heterotrimeric Galpha
      protein-cAMP/PKA signaling pathway positively mediates the sexual development,
      melanin biosynthesis, and secondary metabolism in C. globosum.

PMID- 29652901
TI  - Early postnatal soluble FGFR3 therapy prevents the atypical development of
      obesity in achondroplasia.
AB  - BACKGROUND: Achondroplasia is a rare genetic disease is characterized by abnormal
      bone development and early obesity. While the bone aspect of the disease has been
      thoroughly studied, early obesity affecting approximately 50% of them during
      childhood has been somewhat neglected. It nevertheless represents a major health
      problem in these patients, and is associated to life-threatening complications
      including increasing risk of cardiovascular pathologies. We have thus decided to
      study obesity in patients and to use the mouse model to evaluate if soluble FGFR3
      therapy, an innovative treatment approach for achondroplasia, could also impact
      the development of this significant complication. METHODS AND FINDINGS: To
      achieve this, we have first fully characterized the metabolic deregulations in
      these patients by conducting a longitudinal retrospective study, in children with
      achondroplasia Anthropometric, densitometric measures as well as several blood
      parameters were recorded and compared between three age groups ranging from [0
      3], [4-8] and [9-18] years old. Our results show unexpected results with the
      development of an atypical obesity with preferential fat deposition in the
      abdomen that is remarkably not associated with classical complications of obesity
      such as diabetes or hypercholosterolemia. Because it is not associated with
      diabetes, the atypical obesity has not been studied in the past even though it is
      recognized as a real problem in these patients. These results were validated in a
      murine model of achondroplasia (Fgfr3ach/+) where similar visceral adiposity was
      observed. Unexpected alterations in glucose metabolism were highlighted during
      high-fat diet. Glucose, insulin or lipid levels remained low, without the
      development of diabetes. Very interestingly, in achondroplasia mice treated with
      soluble FGFR3 during the growth period (from D3 to D22), the development of these
      metabolic deregulations was prevented in adult animals (between 4 and 14 weeks of
      age). The lean-over-fat tissues ratio was restored and glucose metabolism showed
      normal levels. Treating Fgfr3ach/+ mice with soluble FGFR3 during the growth
      period, prevented the development of these metabolic deregulations in adult
      animals and restored lean-over-fat tissues ratio as well as glucose metabolism in
      adult animals. CONCLUSION: This study demonstrate that achondroplasia patients
      develop an atypical obesity with preferential abdominal obesity not associated
      with classical complications. These results suggest that achondroplasia induces
      an uncommon metabolism of energy, directly linked to the FGFR3 mutation. These
      data strongly suggest that this common complication of achondroplasia should be
      included in the clinical management of patients. In this context, sFGFR3 proved
      to be a promising treatment for achondroplasia by normalizing the biology at
      different levels, not only restoring bone growth but also preventing the atypical
      visceral obesity and some metabolic deregulations.

PMID- 29652902
TI  - Relations between right ventricular morphology and clinical, electrical and
      genetic parameters in Brugada Syndrome.
AB  - BACKGROUND: Increasing evidence suggests the presence of structural changes
      affecting the right ventricular outflow tract (RVOT) in patients with Brugada
      Syndrome (BrS). The aim of this study was to characterise the RV morphology in
      BrS and explore associations between morphologic, clinical, electrical, and
      genetic parameters using non-invasive multimodality testing. METHODS: Consecutive
      BrS patients (recruited 2013-2015) underwent clinical assessment, dedicated RV
      imaging using cardiac magnetic resonance (CMR) imaging (unless contra-indicated),
      electrical assessment (electrocardiogram, Holter monitoring, signal-averaged
      ECG[SAECG]) and genotyping. Morphologic data were compared to matched control and
      unmatched ARVC (arrhythmogenic right ventricular cardiomyopathy) cohorts, and
      potential associations between morphologic parameters and other variables were
      explored. RESULTS: BrS patients (n = 42, male 86%, age 46+/-12 years) exhibited
      normal global RV volume and function, comparable to control, in contrast to
      significantly larger, impaired RVs in ARVC cohort (RVESV p = 0.0001; RVEDV
      p<0.0001, RVEF p = 0.002). Compared with control, BrS patients exhibited larger
      RVOT volumes (7.4 +/- 0.7 vs 5.8 +/- 0.7 mL/m2, p<0.0001) and wall motion
      abnormalities (RWMA) (31% vs 0%, p = 0.005); compared with ARVC cohort, the RVOT
      volumes were similar (7.4 +/- 0.7 vs, 8.1 +/- 1.7, p = 0.52) and there were less
      RWMA (31% vs 76%, p = 0.01). Overall 67% BrS patients had abnormal RVOT
      morphology. Patients with abnormal RVOT tended to be older (48 +/- 12 y vs 41 +/-
      12y, p = 0.06). Rare genetic variants were only observed in patients with
      abnormal RVOT morphology (36% vs 0%, p = 0.02). CONCLUSIONS: Patients with BrS
      frequently exhibit structural abnormalities localised to the RVOT and these
      changes may be age- and gene-dependent.

PMID- 29652903
TI  - A new method for detecting signal regions in ordered sequences of real numbers,
      and application to viral genomic data.
AB  - We present a fast, robust and parsimonious approach to detecting signals in an
      ordered sequence of numbers. Our motivation is in seeking a suitable method to
      take a sequence of scores corresponding to properties of positions in virus
      genomes, and find outlying regions of low scores. Suitable statistical methods
      without using complex models or making many assumptions are surprisingly lacking.
      We resolve this by developing a method that detects regions of low score within
      sequences of real numbers. The method makes no assumptions a priori about the
      length of such a region; it gives the explicit location of the region and scores
      it statistically. It does not use detailed mechanistic models so the method is
      fast and will be useful in a wide range of applications. We present our approach
      in detail, and test it on simulated sequences. We show that it is robust to a
      wide range of signal morphologies, and that it is able to capture multiple
      signals in the same sequence. Finally we apply it to viral genomic data to
      identify regions of evolutionary conservation within influenza and rotavirus.

PMID- 29652904
TI  - First-night effect on sleep time in dairy cows.
AB  - In human sleep studies, the probability of discomfort from the electrodes and the
      change in environment usually results in first-night recordings being discarded.
      Sleep recordings from the first night in human subjects often differ in amount of
      REM (rapid eye movement) sleep and the overall sleep architecture. This study
      investigated whether recordings of sleep states in dairy cows also show a first
      night effect. Non-invasive electrophysiological recordings were carried out on
      nine cows of the Swedish Red breed during three consecutive 24-hour periods
      (recording days 1-3). Overall, cows spent 12.9 +/- 1.4 hours awake, 8.2 +/- 1
      hours ruminating, 57.2 +/- 20.3 min drowsing, 44.1 +/- 20.2 min in REM sleep and
      64.3 +/- 38.1 min in NREM (non-rapid eye movement) sleep (mean +/- SD) and there
      were no significant differences between recording days in total duration for any
      of the sleep and awake states. However, the bouts of REM sleep and rumination
      were longer, and the awake bouts were shorter, at night time compared to daytime,
      regardless of recording day. The awake bouts also showed an interaction effect
      with longer bouts at daytime during day 1 compared to daytime on day 3. Data on
      sleep and awake states recorded in adult dairy cows during three consecutive 24-h
      periods showed great variation in sleep time between cows, but total time for
      each state was not significantly affected by recording day. Further and more
      detailed studies of how sleep architecture is affected by recording day is
      necessary to fully comprehend the first-night effect in dairy cows.

PMID- 29652905
TI  - Feeding and growth of the marine heterotrophic nanoflagellates, Procryptobia
      sorokini and Paraphysomonas imperforata on a bacterium, Pseudoalteromonas sp.
      with an inducible defence against grazing.
AB  - Heterotrophic marine nanoflagellates are important grazers on bacteria in the
      water column. Some marine bacteria appear more resistant to grazing than do
      others. Marine nanoflagellates can be grown in the laboratory in batch cultures
      fed specific bacterial isolates. In some cultures, the flagellates appear unable
      to completely deplete the bacterial prey even when the bacterial strain otherwise
      is an excellent prey. This may indicate that some marine bacteria are able to
      induce defence mechanisms if they are grazed by nanoflagellates. Four
      morphologically distinct marine heterotrophic nanoflagellates, of which 3 were
      still identified as Procryptobia sorokini (Kinetoplastea) and one as
      Paraphysomonas imperforata (Chrysophyceae) were isolated from a coastal location
      along with 3 isolates of the marine bacterium Pseudoalteromonas sp. Flagellate
      growth and grazing on bacterial prey were analysed in batch cultures.
      Pseudoalteromonas was a suitable prey for all 4 flagellate isolates. They grazed
      and grew on Pseudoalteromonas as sole prey with maximal cell-specific growth
      rates of 0.1-0.25 h-1 and gross growth efficiencies of 38-61%. Exposure to dense
      flagellate cultures or their supernatants did, however, cause a fraction of the
      Pseudoalteromonas cells to aggregate and the bacterium became apparently
      resistant to grazing. Concentrations of suspended Pseudoalteromonas cells were
      therefore not decreased below 1,700-7,500 cells MUL-1 by any of the flagellate
      isolates. These results indicate that Pseudoalteromonas sp. can be an excellent
      prey to marine nanoflagellates but also that is in possession of inducible
      mechanisms that protect against flagellate grazing.

PMID- 29652906
TI  - Mechanical analyses of critical surgical maneuvers in the correction of cleft lip
      nasal deformity.
AB  - The relapse of nasal deformity is a challenge for modern correction of cleft lip.
      A comprehensive understanding in the biomechanical perspective of both the
      formation and correction of the cleft lip nasal deformity would lead to improved
      stability of the corrective outcome. In this study, a finite element model of
      secondary cleft lip nasal deformity was constructed, on which two critical
      corrective maneuvers were mimicked in the form of force-loading. The intercrural
      suture was simulated by a force loaded at the intermediate crus of the alar
      cartilage directing anteriorly and medially, and the suture suspending the alar
      cartilage to the upper lateral cartilage was simulated by a force loaded at the
      lateral crus directing superiorly and medially. The equivalent von-mises stress
      and the total deformation consequent to different patterns of loading were
      captured. Our biomechanical analyses suggested that the intercrural suture at the
      nasal tip might be more effective in generating widespread morphological change
      than the suspension suture, but left much higher level of stress within the skin
      envelope if placed too high. Synergistic effect was observed between the two
      sutures in both the resultant deformation and stress. In addition, our
      simulations were partially supported by clinical photogrammetry data.

PMID- 29652907
TI  - Transcriptomic analysis reveals the differentially expressed genes and pathways
      involved in drought tolerance in pearl millet [Pennisetum glaucum (L.) R. Br].
AB  - Pearl millet is a cereal crop known for its high tolerance to drought, heat and
      salinity stresses as well as for its nutritional quality. The molecular mechanism
      of drought tolerance in pearl millet is unknown. Here we attempted to unravel the
      molecular basis of drought tolerance in two pearl millet inbred lines, ICMB 843
      and ICMB 863 using RNA sequencing. Under greenhouse condition, ICMB 843 was found
      to be more tolerant to drought than ICMB 863. We sequenced the root transcriptome
      from both lines under control and drought conditions using an Illumina Hi-Seq
      platform, generating 139.1 million reads. Mapping of sequenced reads against the
      foxtail millet genome, which has been relatively well-annotated, led to the
      identification of several differentially expressed genes under drought stress.
      Total of 6799 and 1253 differentially expressed genes were found in ICMB 843 and
      ICMB 863, respectively. Pathway and gene function analysis by KEGG online tool
      revealed that the drought response in pearl millet is mainly regulated by
      pathways related to photosynthesis, plant hormone signal transduction and mitogen
      activated protein kinase signaling. The changes in expression of drought
      responsive genes determined by RNA sequencing were confirmed by reverse
      transcription PCR for 7 genes. These results are a first step to understanding
      the molecular mechanisms of drought tolerance in pearl millet and lay a
      foundation for its genetic improvement.

PMID- 29652908
TI  - Automatic lesion detection and segmentation of 18F-FET PET in gliomas: A full 3D
      U-Net convolutional neural network study.
AB  - INTRODUCTION: Amino-acids positron emission tomography (PET) is increasingly used
      in the diagnostic workup of patients with gliomas, including differential
      diagnosis, evaluation of tumor extension, treatment planning and follow-up.
      Recently, progresses of computer vision and machine learning have been translated
      for medical imaging. Aim was to demonstrate the feasibility of an automated 18F
      fluoro-ethyl-tyrosine (18F-FET) PET lesion detection and segmentation relying on
      a full 3D U-Net Convolutional Neural Network (CNN). METHODS: All dynamic 18F-FET
      PET brain image volumes were temporally realigned to the first dynamic
      acquisition, coregistered and spatially normalized onto the Montreal Neurological
      Institute template. Ground truth segmentations were obtained using manual
      delineation and thresholding (1.3 x background). The volumetric CNN was
      implemented based on a modified Keras implementation of a U-Net library with 3
      layers for the encoding and decoding paths. Dice similarity coefficient (DSC) was
      used as an accuracy measure of segmentation. RESULTS: Thirty-seven patients were
      included (26 [70%] in the training set and 11 [30%] in the validation set). All
      11 lesions were accurately detected with no false positive, resulting in a
      sensitivity and a specificity for the detection at the tumor level of 100%. After
      150 epochs, DSC reached 0.7924 in the training set and 0.7911 in the validation
      set. After morphological dilatation and fixed thresholding of the predicted U-Net
      mask a substantial improvement of the DSC to 0.8231 (+ 4.1%) was noted. At the
      voxel level, this segmentation led to a 0.88 sensitivity [95% CI, 87.1 to, 88.2%]
      a 0.99 specificity [99.9 to 99.9%], a 0.78 positive predictive value: [76.9 to
      78.3%], and a 0.99 negative predictive value [99.9 to 99.9%]. CONCLUSIONS: With
      relatively high performance, it was proposed the first full 3D automated
      procedure for segmentation of 18F-FET PET brain images of patients with different
      gliomas using a U-Net CNN architecture.

PMID- 29652909
TI  - Estimation of universal and taxon-specific parameters of prokaryotic genome
      evolution.
AB  - The results of our recent study on mathematical modeling of microbial genome
      evolution indicate that, on average, genomes of bacteria and archaea evolve in
      the regime of mutation-selection balance defined by positive selection
      coefficients associated with gene acquisition that is counter-acted by the
      intrinsic deletion bias. This analysis was based on the strong assumption that
      parameters of genome evolution are universal across the diversity of bacteria and
      archaea, and yielded extremely low values of the selection coefficient. Here we
      further refine the modeling approach by taking into account evolutionary factors
      specific for individual groups of microbes using two independent fitting
      strategies, an ad hoc hard fitting scheme and a mixture model. The resulting
      estimate of the mean selection coefficient of s~10-10 associated with the gain of
      one gene implies that, on average, acquisition of a gene is beneficial, and that
      microbial genomes typically evolve under a weak selection regime that might
      transition to strong selection in highly abundant organisms with large effective
      population sizes. The apparent selective pressure towards larger genomes is
      balanced by the deletion bias, which is estimated to be consistently greater than
      unity for all analyzed groups of microbes. The estimated values of s are more
      realistic than the lower values obtained previously, indicating that global and
      group-specific evolutionary factors synergistically affect microbial genome
      evolution that seems to be driven primarily by adaptation to existence in diverse
      niches.

PMID- 29652910
TI  - Elderly dendritic cells respond to LPS/IFN-gamma and CD40L stimulation despite
      incomplete maturation.
AB  - There is evidence that dendritic cells (DCs) undergo age-related changes that
      modulate their function with their key role being priming antigen-specific
      effector T cells. This occurs once DCs develop into antigen-presenting cells in
      response to stimuli/danger signals. However, the effects of aging on DC responses
      to bacterial lipopolysaccharide (LPS), the pro-inflammatory cytokine interferon
      (IFN)-gamma and CD40 ligand (CD40L) have not yet been systematically evaluated.
      We examined responses of blood myeloid (m)DC1s, mDC2s, plasmacytoid (p)DCs, and
      monocyte-derived DCs (MoDCs) from young (21-40 years) and elderly (60-84 years)
      healthy human volunteers to LPS/IFN-gamma or CD40L stimulation. All elderly DC
      subsets demonstrated comparable up-regulation of co-stimulatory molecules (CD40,
      CD80 and/or CD86), intracellular pro-inflammatory cytokine levels (IFN-gamma,
      tumour necrosis factor (TNF)-alpha, IL-6 and/or IL-12), and/or secreted cytokine
      levels (IFN-alpha, IFN-gamma, TNF-alpha, and IL-12) to their younger
      counterparts. Furthermore, elderly-derived LPS/IFN-gamma or CD40L-activated MoDCs
      induced similar or increased levels of CD8+ and CD4+ T cell proliferation, and
      similar T cell functional phenotypes, to their younger counterparts. However,
      elderly LPS/IFN-gamma-activated MoDCs were unreliable in their ability to up
      regulate chemokine (IL-8 and monocyte chemoattractant protein (MCP)-1) and IL-6
      secretion, implying an inability to dependably induce an inflammatory response. A
      key age-related difference was that, unlike young-derived MoDCs that completely
      lost their ability to process antigen, elderly-derived MoDCs maintained their
      antigen processing ability after LPS/IFN-gamma maturation, measured using the DQ
      ovalbumin assay; this response implies incomplete maturation that may enable
      elderly DCs to continuously present antigen. These differences may impact on the
      efficacy of anti-pathogen and anti-tumour immune responses in the elderly.

PMID- 29652911
TI  - Pharmacogenetic landscape of Metabolic Syndrome components drug response in
      Tunisia and comparison with worldwide populations.
AB  - Genetic variation is an important determinant affecting either drug response or
      susceptibility to adverse drug reactions. Several studies have highlighted the
      importance of ethnicity in influencing drug response variability that should be
      considered during drug development. Our objective is to characterize the genetic
      variability of some pharmacogenes involved in the response to drugs used for the
      treatment of Metabolic Syndrome (MetS) in Tunisia and to compare our results to
      the worldwide populations. A set of 135 Tunisians was genotyped using the
      Affymetrix Chip 6.0 genotyping array. Variants located in 24 Very Important
      Pharmacogenes (VIP) involved in MetS drug response were extracted from the
      genotyping data. Analysis of variant distribution in Tunisian population compared
      to 20 worldwide populations publicly available was performed using R software
      packages. Common variants between Tunisians and the 20 investigated populations
      were extracted from genotyping data. Multidimensional screening showed that
      Tunisian population is clustered with North African and European populations. The
      greatest divergence was observed with the African and Asian population. In
      addition, we performed Inter-ethnic comparison based on the genotype frequencies
      of five VIP biomarkers. The genotype frequencies of the biomarkers rs3846662,
      rs1045642, rs7294 and rs12255372 located respectively in HMGCR, ABCB1, VKORC1 and
      TCF7L2 are similar between Tunisian, Tuscan (TSI) and European (CEU). The
      genotype frequency of the variant rs776746 located in CYP3A5 gene is similar
      between Tunisian and African populations and different from CEU and TSI. The
      present study shows that the genetic make up of the Tunisian population is
      relatively complex in regard to pharmacogenes and reflects previous historical
      events. It is important to consider this ethnic difference in drug prescription
      in order to optimize drug response to avoid serious adverse drug reactions.
      Taking into account similarities with other neighboring populations, our study
      has an impact not only on the Tunisian population but also on North African
      population which are underrepresented in pharmacogenomic studies.

PMID- 29652912
TI  - Virtual screening by a new Clustering-based Weighted Similarity Extreme Learning
      Machine approach.
AB  - Machine learning techniques are becoming popular in virtual screening tasks. One
      of the powerful machine learning algorithms is Extreme Learning Machine (ELM)
      which has been applied to many applications and has recently been applied to
      virtual screening. We propose the Weighted Similarity ELM (WS-ELM) which is based
      on a single layer feed-forward neural network in a conjunction of 16 different
      similarity coefficients as activation function in the hidden layer. It is known
      that the performance of conventional ELM is not robust due to random weight
      selection in the hidden layer. Thus, we propose a Clustering-based WS-ELM (CWS
      ELM) that deterministically assigns weights by utilising clustering algorithms
      i.e. k-means clustering and support vector clustering. The experiments were
      conducted on one of the most challenging datasets-Maximum Unbiased Validation
      Dataset-which contains 17 activity classes carefully selected from PubChem. The
      proposed algorithms were then compared with other machine learning techniques
      such as support vector machine, random forest, and similarity searching. The
      results show that CWS-ELM in conjunction with support vector clustering yields
      the best performance when utilised together with Sokal/Sneath(1) coefficient.
      Furthermore, ECFP_6 fingerprint presents the best results in our framework
      compared to the other types of fingerprints, namely ECFP_4, FCFP_4, and FCFP_6.

PMID- 29652913
TI  - Ventilator-associated pneumonia in patients assisted by veno-arterial
      extracorporeal membrane oxygenation support: Epidemiology and risk factors of
      treatment failure.
AB  - INTRODUCTION: Ventilator-associated pneumonia (VAP) is frequent in Intensive Care
      Unit (ICU) patients. In the specific case of patients treated with Veno-Arterial
      Extracorporeal Membrane Oxygenation Support (VA-ECMO), VAP treatment failures
      (VAP-TF) have been incompletely investigated. METHODS: To investigate the risk
      factors of treatment failure (VAP-TF) in a large cohort of ICU patients treated
      with VA-ECMO, we conducted a retrospective study in a Surgical ICU about patients
      assisted with VA-ECMO between January 1, 2013, and December 31, 2014. Diagnosis
      of VAP was confirmed by a positive quantitative culture of a respiratory sample.
      VAP-TF was defined as composite of death attributable to pneumonia and relapse
      within 28 days of the first episode. RESULTS: In total, 152 patients underwent
      ECMO support for > 48h. During the VA-ECMO support, 85 (55.9%) patients developed
      a VAP, for a rate of 60.6 per 1000 ECMO days. The main pathogens identified were
      Pseudomonas aeruginosa and Enterobacteriaceae. VAP-TF occurred in 37.2% of
      patients and was associated with an increased 28-day mortality (Hazard Ratio 3.05
      [1.66; 5.63], P<0.001), and VA-ECMO assistance duration (HR 1.47 [1.05-2.05], P =
      0.025). Risk factors for VAP-TF were renal replacement therapy (HR 13.05 [1.73;
      98.56], P = 0.013) and documentation of Pseudomonas aeruginosa (HR 2.36 [1.04;
      5.35], P = 0.04). CONCLUSIONS: VAP in patients treated with VA-ECMO is associated
      with an increased morbidity and mortality. RRT and infection by Pseudomonas
      aeruginosa appear as strong risks factors of treatment failure. Further studies
      seem necessary to precise the best antibiotic management in these patients.

PMID- 29652914
TI  - Intestinal manipulation affects mucosal antimicrobial defense in a mouse model of
      postoperative ileus.
AB  - AIM: To explore the effects of abdominal surgery and interleukin-1 signaling on
      antimicrobial defense in a model of postoperative ileus. METHODS: C57BL/6 and
      Interleukin-1 receptor type I (IL-1R1) deficient mice underwent intestinal
      manipulation to induce POI. Expression of mucosal IL-1alpha, IL-1beta and IL-1R1
      and several antimicrobial peptides and enzymes were measured by quantitative PCR
      or ELISA, western blotting or immunohistochemistry. Bacterial overgrowth was
      determined by fluorescent in-situ hybridization and counting of jejunal luminal
      bacteria. Translocation of aerobic and anaerobic bacteria into the intestinal
      wall, mesenteric lymph nodes, liver and spleen was determined by counting
      bacterial colonies on agar plates 48h after plating of tissue homogenates.
      Antimicrobial activity against E. coli and B. vulgatus was analyzed in total and
      cationic fractions of small bowel mucosal tissue homogenates by a flow cytometry
      based bacterial depolarization assay. RESULTS: Jejunal bacterial overgrowth was
      detected 24h after surgery. At the same time point, but not in the early phase 3h
      after surgery, bacterial translocation into the liver and mesenteric lymph nodes
      was observed. Increased antimicrobial activity against E. coli was induced within
      early phase of POI. Basal antimicrobial peptide and enzyme gene expression was
      higher in the ileal compared to the jejunal mucosa. The expression of lysozyme 1,
      cryptdin 1, cryptdin 4 and mucin 2 were reduced 24h after surgery in the ileal
      mucosa and mucin 2 was also reduced in the jejunum. Postoperative IL-1alpha and
      IL-1beta were increased in the postoperative mucosa. Deficiency of IL-1R1
      affected the expression of antimicrobial peptides during homeostasis and POI.
      CONCLUSION: Small bowel antimicrobial capacity is disturbed during POI which is
      accompanied by bacterial overgrowth and translocation. IL-1R1 is partially
      involved in the gene expression of mucosal antimicrobial peptides. Altered small
      bowel antimicrobial activity may contribute also to POI development and
      manifestation in patients undergoing abdominal surgery.

PMID- 29652916
TI  - Spatial structural characteristics of forests dominated by Pinus tabulaeformis
      Carr.
AB  - The Chinese pine (Pinus tabulaeformis Carr.) is an ecologically and economically
      important evergreen coniferous tree which dominates warm temperate forests
      throughout northern China. We established two permanent plots within the Chinese
      pine forest in the Jiulong Mountains, Beijing, China. To understand the
      structural characteristics and dynamics of these plots, we analyzed the spatial
      structural characteristics within nearest-neighbor relationships using the
      bivariate distributions of the stand spatial structural parameters: uniform angle
      index, W; mingling index, M; dominance index, U; and crowding index, C. Results
      revealed that most trees in the forest were randomly distributed. The predominant
      individuals and randomly arranged trees were in very dense areas and surrounded
      by the same species. In addition, both plots exhibited a uniform size
      differentiation pattern. The two plots differed mainly in the level of species
      mixture and dominance. The majority of reference trees in the pure Chinese pine
      forest (plot 1) exhibited poor species mingling and low dominance, whereas trees
      in the mixed Chinese pine forest (plot 2) were evenly distributed in each
      mingling class and most trees were of intermediate dominance. The study results
      are useful for optimizing forest management activities in the studied stands,
      promoting tree growth, regeneration and habitat diversity, and improving forest
      quality at a fine scale.

PMID- 29652915
TI  - Protein kinase D3 modulates MMP1 and MMP13 expression in human chondrocytes.
AB  - Many catabolic stimuli, including interleukin-1 (IL-1) in combination with
      oncostatin M (OSM), promote cartilage breakdown via the induction of collagen
      degrading collagenases such as matrix metalloproteinase 1 (MMP1) and MMP13 in
      human articular chondrocytes. Indeed, joint diseases with an inflammatory
      component are characterised by excessive extracellular matrix (ECM) catabolism.
      Importantly, protein kinase C (PKC) signalling has a primary role in cytokine
      induced MMP1/13 expression, and is known to regulate cellular functions
      associated with pathologies involving ECM remodelling. At present, substrates
      downstream of PKC remain undefined. Herein, we show that both IL-1- and OSM
      induced phosphorylation of protein kinase D (PKD) in human chondrocytes is
      strongly associated with signalling via the atypical PKCiota isoform.
      Consequently, inhibiting PKD activation with a pan-PKD inhibitor significantly
      reduced the expression of MMP1/13. Specific gene silencing of the PKD isoforms
      revealed that only PKD3 (PRKD3) depletion mirrored the observed MMP repression,
      indicative of the pharmacological inhibitor specifically affecting only this
      isoform. PRKD3 silencing was also shown to reduce serine phosphorylation of
      signal transducer and activator of transcription 3 (STAT3) as well as
      phosphorylation of all three mitogen-activated protein kinase groups. This
      altered signalling following PRKD3 silencing led to a significant reduction in
      the expression of the activator protein-1 (AP-1) genes FOS and JUN, critical for
      the induction of many MMPs including MMP1/13. Furthermore, the AP-1 factor
      activating transcription factor 3 (ATF3) was also reduced concomitant with the
      observed reduction in MMP13 expression. Taken together, we highlight an important
      role for PKD3 in the pro-inflammatory signalling that promotes cartilage
      destruction.

PMID- 29652917
TI  - Prevalent hepatitis B surface antigen among first-time blood donors in Gabon.
AB  - Despite chronic Hepatitis B virus (HBV) infection being the main cause of younger
      onset complex liver disease including cirrhosis and hepatocellular carcinoma
      (HCC) in Africa, very little is known regarding the seroprevalence of HBV in the
      Gabonese general population. This investigation aimed to provide strong
      epidemiological data and risk factors associated with HBV infection in first-time
      blood donors representative of the urban adult population. The screening of HBsAg
      was carried out using 4th generation ELISA kits. The overall seroprevalence of
      HBsAg was 7.28%. The frequency of HBsAg was differential and marked by annual
      variations in blood donors from 2009 to 2016. Seroprevalence was 2-fold higher
      among males versus females (OR = 1.90 (95% CI: 1.75-2.06), P<0.001). HBsAg
      seroprevalence was significantly higher in donors of the age group 25-35 years
      old compared to donors of the age group <18 years (OR = 1.64 (95% CI: 1.03-2.60),
      P = 0.04). The seroprevalence of HBsAg in family/replacement donors (FRD) was
      significantly higher than that of voluntary non-remunerated donors (VNRD) (OR =
      0.88 (95% CI: 0.83-0.94), P <0.001). The simultaneous comparison of HBsAg
      seroprevalence with blood donation type, gender and age showed that the higher
      prevalence in FRD was significant only in males between 18 and 45 years and in
      females between 25 and 34 years of age. This study confirms the high endemicity
      of HBV in Gabon while identifying the most infected age groups for both men and
      women.

PMID- 29652918
TI  - A genome-wide association study of red-blood cell fatty acids and ratios
      incorporating dietary covariates: Framingham Heart Study Offspring Cohort.
AB  - Recent analyses have suggested a strong heritable component to circulating fatty
      acid (FA) levels; however, only a limited number of genes have been identified
      which associate with FA levels. In order to expand upon a previous genome wide
      association study done on participants in the Framingham Heart Study Offspring
      Cohort and FA levels, we used data from 2,400 of these individuals for whom red
      blood cell FA profiles, dietary information and genotypes are available, and then
      conducted a genome-wide evaluation of potential genetic variants associated with
      22 FAs and 15 FA ratios, after adjusting for relevant dietary covariates. Our
      analysis found nine previously identified loci associated with FA levels (FADS,
      ELOVL2, PCOLCE2, LPCAT3, AGPAT4, NTAN1/PDXDC1, PKD2L1, HBS1L/MYB and
      RAB3GAP1/MCM6), while identifying four novel loci. The latter include an
      association between variants in CALN1 (Chromosome 7) and eicosapentaenoic acid
      (EPA), DHRS4L2 (Chromosome 14) and a FA ratio measuring delta-9-desaturase
      activity, as well as two loci associated with less well understood proteins.
      Thus, the inclusion of dietary covariates had a modest impact, helping to uncover
      four additional loci. While genome-wide association studies continue to uncover
      additional genes associated with circulating FA levels, much of the heritable
      risk is yet to be explained, suggesting the potential role of rare genetic
      variation, epistasis and gene-environment interactions on FA levels as well.
      Further studies are needed to continue to understand the complex genetic picture
      of FA metabolism and synthesis.

PMID- 29652919
TI  - Preparation and characterization of Fe3O4@Au-C225 composite targeted
      nanoparticles for MRI of human glioma.
AB  - OBJECTIVE: To study the characterization of Fe3O4@Au-C225 composite targeted
      MNPs. METHODS: Fe3O4@Au-C225 was prepared by the absorption method. The
      immunosorbent assay was used to evaluate its absorption efficiency at C225 Fc.
      ZETA SIZER3000 laser particle size analyzer, ultraviolet photometer and its
      characteristics were analyzed by VSM. the targeting effect of Fe3O4@Au-C225
      composite targeted MNPs on U251 cells in vitro were detected by 7.0 Tesla Micro
      MR; and subcutaneous transplanted human glioma in nude mice were performed the
      targeting effect in vivo after tail vein injection of Fe3O4@Au-C225 composite
      targeted MNPs by MRI. RESULTS: The self-prepared Fe3O4@Au composite MNPs can
      adsorb C225 with high efficiency of adsorption so that Fe3O4@Au-C225 composite
      targeted MNPs were prepared successfully. Fe3O4@Au-C225 composite targeted MNPs
      favorably targeted human glioma cell line U251 in vitro; Fe3O4@Au-C225 composite
      targeted MNPs have good targeting ability to xenografted glioma on nude mice in
      vivo, and can be traced by MRI. CONCLUSION: The Fe3O4@Au-C225 composite targeted
      MNPs have the potential to be used as a tracer for glioma in vivo.

PMID- 29652920
TI  - Association of renal hyperfiltration with incident proteinuria - A nationwide
      registry study.
AB  - To elucidate the association between renal hyperfiltration (RHF) and incident
      proteinuria, the data from 11,559,520 Korean adults who had undergone health
      screenings >= 3 times between 2009 and 2014 and had glomerular filtration rate
      (GFR) >=60 mL/min/1.73m2 and negative dipstick test for proteinuria at baseline,
      were retrospectively analyzed. GFR was estimated with the Chronic Kidney Disease
      Epidemiology Collaboration equation based on serum creatinine, and RHF was
      defined as GFR >95th percentile adjusted for sex, age, body size, and diabetes
      and/or hypertension medication. The adjusted hazard ratio (aHR) of incident
      proteinuria in the RHF was 1.083 (95% CI, 1.069~1.097) compared to that of the
      non-RHF with Cox regression model. The association between RHF and incident
      proteinuria was not only in diabetic but also in non-diabetic subjects. This
      association was not observed in women (p for interaction <0.001). A reverse J
      shaped association was found between the adjusted GFR slope and aHR of incident
      proteinuria. Both lower and higher GFR were associated with incident proteinuria
      in men. In conclusion, RHF was associated with incident proteinuria in men.
      Clinical studies are necessary to study whether the alleviation of RHF can
      prevent incident proteinuria.

PMID- 29652921
TI  - The importance of regional models in assessing canine cancer incidences in
      Switzerland.
AB  - Fitting canine cancer incidences through a conventional regression model assumes
      constant statistical relationships across the study area in estimating the model
      coefficients. However, it is often more realistic to consider that these
      relationships may vary over space. Such a condition, known as spatial non
      stationarity, implies that the model coefficients need to be estimated locally.
      In these kinds of local models, the geographic scale, or spatial extent, employed
      for coefficient estimation may also have a pervasive influence. This is because
      important variations in the local model coefficients across geographic scales may
      impact the understanding of local relationships. In this study, we fitted canine
      cancer incidences across Swiss municipal units through multiple regional models.
      We computed diagnostic summaries across the different regional models, and
      contrasted them with the diagnostics of the conventional regression model, using
      value-by-alpha maps and scalograms. The results of this comparative assessment
      enabled us to identify variations in the goodness-of-fit and coefficient
      estimates. We detected spatially non-stationary relationships, in particular, for
      the variables related to biological risk factors. These variations in the model
      coefficients were more important at small geographic scales, making a case for
      the need to model canine cancer incidences locally in contrast to more
      conventional global approaches. However, we contend that prior to undertaking
      local modeling efforts, a deeper understanding of the effects of geographic scale
      is needed to better characterize and identify local model relationships.

PMID- 29652922
TI  - A novel mechanism of RNase L inhibition: Theiler's virus L* protein prevents 2-5A
      from binding to RNase L.
AB  - The OAS/RNase L pathway is one of the best-characterized effector pathways of the
      IFN antiviral response. It inhibits the replication of many viruses and
      ultimately promotes apoptosis of infected cells, contributing to the control of
      virus spread. However, viruses have evolved a range of escape strategies that act
      against different steps in the pathway. Here we unraveled a novel escape strategy
      involving Theiler's murine encephalomyelitis virus (TMEV) L* protein. Previously
      we found that L* was the first viral protein binding directly RNase L. Our
      current data show that L* binds the ankyrin repeats R1 and R2 of RNase L and
      inhibits 2'-5' oligoadenylates (2-5A) binding to RNase L. Thereby, L* prevents
      dimerization and oligomerization of RNase L in response to 2-5A. Using chimeric
      mouse hepatitis virus (MHV) expressing TMEV L*, we showed that L* efficiently
      inhibits RNase L in vivo. Interestingly, those data show that L* can functionally
      substitute for the MHV-encoded phosphodiesterase ns2, which acts upstream of L*
      in the OAS/RNase L pathway, by degrading 2-5A.

PMID- 29652924
TI  - Extended cleavage specificity of human neutrophil cathepsin G: A low activity
      protease with dual chymase and tryptase-type specificities.
AB  - Human neutrophils express at least four active serine proteases, cathepsin G, N
      elastase, proteinase 3 and neutrophil serine protease 4 (NSP4). They have all
      been extensively studied due to their importance in neutrophil biology and
      immunity. However, their extended cleavage specificities have never been
      determined in detail. Here we present a detailed cleavage specificity analysis of
      human cathepsin G (hCG). The specificity was determined by phage display analysis
      and the importance of individual amino acids in and around the cleavage site was
      then validated using novel recombinant substrates. To provide a broader context
      to this serine protease, a comparison was made to the related mast cell protease,
      human chymase (HC). hCG showed similar characteristics to HC including both the
      primary and extended specificities. As expected, Phe, Tyr, Trp and Leu were
      preferred in the P1 position. In addition, both proteases showed a preference for
      negatively charged amino acids in the P2' position of substrates and a preference
      for aliphatic amino acids both upstream and downstream of the cleavage site.
      However, overall the catalytic activity of hCG was ~10-fold lower than HC. hCG
      has previously been reported to have a dual specificity consisting of chymase and
      tryptase-type activities. In our analysis, tryptase activity against substrates
      with Lys in P1 cleavage position was indeed only 2-fold less efficient as
      compared to optimal chymase substrates supporting strong dual-type specificity.
      We hope the information presented here on extended cleavage specificities of hCG
      and HC will assist in the search for novel in vivo substrates for these proteases
      as well as aid in the efforts to better understand the role of hCG in immunity
      and bacterial defence.

PMID- 29652923
TI  - Limited immune surveillance in lymphoid tissue by cytolytic CD4+ T cells during
      health and HIV disease.
AB  - CD4+ T cells subsets have a wide range of important helper and regulatory
      functions in the immune system. Several studies have specifically suggested that
      circulating effector CD4+ T cells may play a direct role in control of HIV
      replication through cytolytic activity or autocrine beta-chemokine production.
      However, it remains unclear whether effector CD4+ T cells expressing cytolytic
      molecules and beta-chemokines are present within lymph nodes (LNs), a major site
      of HIV replication. Here, we report that expression of beta-chemokines and
      cytolytic molecules are enriched within a CD4+ T cell population with high levels
      of the T-box transcription factors T-bet and eomesodermin (Eomes). This effector
      population is predominately found in peripheral blood and is limited in LNs
      regardless of HIV infection or treatment status. As a result, CD4+ T cells
      generally lack effector functions in LNs, including cytolytic capacity and
      IFNgamma and beta-chemokine expression, even in HIV elite controllers and during
      acute/early HIV infection. While we do find the presence of degranulating CD4+ T
      cells in LNs, these cells do not bear functional or transcriptional effector T
      cell properties and are inherently poor to form stable immunological synapses
      compared to their peripheral blood counterparts. We demonstrate that CD4+ T cell
      cytolytic function, phenotype, and programming in the peripheral blood is
      dissociated from those characteristics found in lymphoid tissues. Together, these
      data challenge our current models based on blood and suggest spatially and
      temporally dissociated mechanisms of viral control in lymphoid tissues.

PMID- 29652925
TI  - The ecology of immune state in a wild mammal, Mus musculus domesticus.
AB  - The immune state of wild animals is largely unknown. Knowing this and what
      affects it is important in understanding how infection and disease affects wild
      animals. The immune state of wild animals is also important in understanding the
      biology of their pathogens, which is directly relevant to explaining pathogen
      spillover among species, including to humans. The paucity of knowledge about wild
      animals' immune state is in stark contrast to our exquisitely detailed
      understanding of the immunobiology of laboratory animals. Making an immune
      response is costly, and many factors (such as age, sex, infection status, and
      body condition) have individually been shown to constrain or promote immune
      responses. But, whether or not these factors affect immune responses and immune
      state in wild animals, their relative importance, and how they interact (or do
      not) are unknown. Here, we have investigated the immune ecology of wild house
      mice-the same species as the laboratory mouse-as an example of a wild mammal,
      characterising their adaptive humoral, adaptive cellular, and innate immune
      state. Firstly, we show how immune variation is structured among mouse
      populations, finding that there can be extensive immune discordance among
      neighbouring populations. Secondly, we identify the principal factors that
      underlie the immunological differences among mice, showing that body condition
      promotes and age constrains individuals' immune state, while factors such as
      microparasite infection and season are comparatively unimportant. By applying a
      multifactorial analysis to an immune system-wide analysis, our results bring a
      new and unified understanding of the immunobiology of a wild mammal.

PMID- 29652926
TI  - Assessment of costs associated with adverse events in patients with cancer.
AB  - Adverse event (AE)-related costs represent an important component of economic
      models for cancer care. However, since previous studies mostly focused on
      specific AEs, treatments, or cancer types, limited information is currently
      available. Therefore, this study assessed the incremental healthcare costs
      associated with a large number of AEs among patients diagnosed with some of the
      most prevalent types of cancer. Data were obtained from a large US claims
      database. Adult patients were included if diagnosed with and treated for one of
      the following cancer types: breast, digestive organs and peritoneum,
      genitourinary organs (including bladder and ovary and other uterine adnexa),
      lung, lymphatic and hematopoietic tissue, and skin. Treatment episodes were
      defined as the period from initiation of the first antineoplastic pharmacologic
      therapy to discontinuation (i.e., gap of >= 45 days), or change in treatment
      regimen, or end of data availability. A total of 36 AEs were selected from the
      product inserts of 104 treatments recommended by practice guidelines. A
      retrospective matched cohort design was used, matching a treatment episode with a
      certain AE with a treatment episode without that AE. A total of 412,005 patients
      were selected, for a total of 794,243 treatment episodes, resulting in 1,617,368
      matched treatment episodes across all 36 AEs. Incremental healthcare costs
      associated with AEs of any severity ranged from $546 for cough/upper respiratory
      infections to $24,633 for gastrointestinal perforation. The three most costly AEs
      when considering any severity were gastrointestinal perforation ($24,633),
      central nervous system hemorrhage ($24,322), and sepsis/septicemia ($23,510).
      Incremental healthcare costs associated with severe AEs ranged from $15,709 for
      dermatitis and rash to $48,538 for gastrointestinal fistula. The three most
      costly severe AEs were gastrointestinal fistula ($48,538), gastrointestinal
      perforation ($41,281), and central nervous system hemorrhage ($38,428). In
      conclusion, AEs during treatment episodes for cancer were frequent and associated
      with a substantial economic burden.

PMID- 29652927
TI  - Public perceptions of emergency decontamination: Effects of intervention type and
      responder management strategy during a focus group study.
AB  - In the event of an incident involving the release of a hazardous chemical, first
      responders may decide to initiate emergency decontamination in order to remove
      any contaminant from affected casualties. Recent initiatives such as the UK Home
      Office-led Initial Operational Response Programme have introduced new evidence
      based decontamination protocols that reduce the time taken to initiate the
      decontamination process, including an increased emphasis on rapidly removing
      contaminated clothing (disrobe), and the use of improvised dry decontamination
      methods. The current study used a series of focus groups to examine public
      perceptions of different decontamination interventions and responder management
      strategies. Results revealed that a decontamination shower was perceived to be
      more effective than dry decontamination methods and that a management strategy
      that included effective responder communication resulted in increased willingness
      to comply with the need for decontamination. This study demonstrates that public
      understanding and acceptance of novel decontamination methods such as dry
      decontamination may present additional challenges for first responders. Increased
      emphasis on effective communication during decontamination is needed.
      Furthermore, provision of information during the focus group study resulted in an
      increase in participants' knowledge and confidence in taking recommended
      decontamination actions, which was maintained three months after the study. The
      longitudinal nature of these effects suggest that it may be possible to increase
      public awareness about actions to take during chemical incidents by developing
      pre-incident public education; however, further research is needed to examine
      this more fully.

PMID- 29652928
TI  - Correction: The effects of patient cost sharing on inpatient utilization, cost,
      and outcome.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0187096.].

PMID- 29652929
TI  - Immunogenicity and safety of three consecutive production lots of the non
      replicating smallpox vaccine MVA: A randomised, double blind, placebo controlled
      phase III trial.
AB  - BACKGROUND: Modified Vaccinia Ankara (MVA) is a live, viral vaccine under
      advanced development as a non-replicating smallpox vaccine. A randomised, double
      blind, placebo-controlled phase III clinical trial was conducted to demonstrate
      the humoral immunogenic equivalence of three consecutively manufactured MVA
      production lots, and to confirm the safety and tolerability of MVA focusing on
      cardiac readouts. METHODS: The trial was conducted at 34 sites in the US.
      Vaccinia-naive adults aged 18-40 years were randomly allocated to one of four
      groups using a 1:1:1:1 randomization scheme. Subjects received either two MVA
      injections from three consecutive lots (Groups 1-3), or two placebo injections
      (Group 4), four weeks apart. Everyone except personnel involved in vaccine
      handling and administration was blinded to treatment. Safety assessment focused
      on cardiac monitoring throughout the trial. Vaccinia-specific antibody titers
      were measured using a Plaque Reduction Neutralization Test (PRNT) and an Enzyme
      Linked Immunosorbent Assay (ELISA). The primary immunogenicity endpoint was
      Geometric Mean Titers (GMTs) after two MVA vaccinations measured by PRNT at trial
      visit 4. This trial is registered with ClinicalTrials.gov, number NCT01144637.
      RESULTS: Between March 2013 and May 2014, 4005 subjects were enrolled and
      received at least one injection of MVA (n = 3003) or placebo (n = 1002). The
      three MVA lots induced equivalent antibody titers two weeks after the second
      vaccination, with seroconversion rates of 99.8% (PRNT) and 99.7% (ELISA).
      Overall, 180 (6.0%) subjects receiving MVA and 29 (2.9%) subjects in the placebo
      group reported at least one unsolicited Adverse Event (AE) that was considered
      trial-related. Vaccination was well tolerated without significant safety
      concerns, particularly regarding cardiac assessment. CONCLUSIONS: The
      neutralizing and total antibody titers induced by each of the three lots were
      equivalent. No significant safety concerns emerged in this healthy trial
      population, especially regarding cardiac safety, thus confirming the excellent
      safety and tolerability profile of MVA. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT01144637.

PMID- 29652931
TI  - Correction: Network evolution model for supply chain with manufactures as the
      core.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0191180.].

PMID- 29652930
TI  - Tissue maintenance of CMV-specific inflationary memory T cells by IL-15.
AB  - Cytomegalovirus (CMV) infection induces an atypical CD8 T cell response, termed
      inflationary, that is characterised by accumulation and maintenance of high
      numbers of effector memory like cells in circulation and peripheral tissues-a
      feature being successfully harnessed for vaccine purposes. Although stability of
      this population depends on recurrent antigen encounter, the requirements for
      prolonged survival in peripheral tissues remain unknown. Here, we reveal that
      murine CMV-specific inflationary CD8 T cells are maintained in an antigen
      independent manner and have a half-life of 12 weeks in the lung tissue. This half
      life is drastically longer than the one of phenotypically comparable inflationary
      effector cells. IL-15 alone, and none of other common gamma-cytokines, was
      crucial for survival of inflationary cells in peripheral organs. IL-15, mainly
      produced by non-hematopoietic cells in lung tissue and being trans-presented,
      promoted inflationary T cell survival by increasing expression of Bcl-2. These
      results indicate that inflationary CD8 T cells are not just simply effector-like
      cells, rather they share properties of both effector and memory CD8 T cells and
      they appear to be long-lived cells compared to the effector cells from acute
      virus infections.

PMID- 29652932
TI  - Analysis of length of hospital stay using electronic health records: A
      statistical and data mining approach.
AB  - BACKGROUND: The length of stay (LOS) is an important indicator of the efficiency
      of hospital management. Reduction in the number of inpatient days results in
      decreased risk of infection and medication side effects, improvement in the
      quality of treatment, and increased hospital profit with more efficient bed
      management. The purpose of this study was to determine which factors are
      associated with length of hospital stay, based on electronic health records, in
      order to manage hospital stay more efficiently. MATERIALS AND METHODS: Research
      subjects were retrieved from a database of patients admitted to a tertiary
      general university hospital in South Korea between January and December 2013.
      Patients were analyzed according to the following three categories: descriptive
      and exploratory analysis, process pattern analysis using process mining
      techniques, and statistical analysis and prediction of LOS. RESULTS: Overall, 55%
      (25,228) of inpatients were discharged within 4 days. The department of
      rehabilitation medicine (RH) had the highest average LOS at 15.9 days. Of all the
      conditions diagnosed over 250 times, diagnoses of I63.8 (cerebral infarction,
      middle cerebral artery), I63.9 (infarction of middle cerebral artery territory)
      and I21.9 (myocardial infarction) were associated with the longest average
      hospital stay and high standard deviation. Patients with these conditions were
      also more likely to be transferred to the RH department for rehabilitation. A
      range of variables, such as transfer, discharge delay time, operation frequency,
      frequency of diagnosis, severity, bed grade, and insurance type was significantly
      correlated with the LOS. CONCLUSIONS: Accurate understanding of the factors
      associating with the LOS and progressive improvements in processing and
      monitoring may allow more efficient management of the LOS of inpatients.

PMID- 29652933
TI  - RhoGAPp190: A potential player in tbph-mediated neurodegeneration in Drosophila.
AB  - TDP-43 is an ubiquitous and highly conserved ribonucleoprotein involved in
      several cellular processes including pre-mRNA splicing, transcription, mRNA
      stability and transport. Notwithstanding the evidence of TDP-43 involvement in
      the pathogenesis of different neurodegenerative disorders (i.e. ALS and FTLD),
      the underlying mechanisms are still unclear. Given the high degree of functional
      similarity between the human and fly orthologs of TDP-43, Drosophila melanogaster
      is a simple and useful model to study the pathophysiological role of this protein
      in vivo. It has been demonstrated that the depletion of the TDP-43 fly ortholog
      (tbph) induces deficient locomotive behaviors and reduces life span and
      anatomical defects at the neuromuscular junction. In this study, using the known
      binding specificity of TDP-43/tbph for (UG) repeated sequences, we performed a
      bioinformatic screening for fly genes with at least 6 (TG) repeats in a row
      within the 3'-UTR regions in order to identify the genes that might be regulated
      by this factor. Among these genes, we were able to identify RhoGAPp190 as a
      potential target of the tbph-mediated neurodegeneration. RhoGAPp190 is a negative
      regulator of Drosophila RhoA, a GTPase protein implicated in the fine modulation
      of critical cellular processes including axon branch stability and motor axon
      defasciculation at muscle level and cognitive processes. We were able to
      demonstrate that the RhoGAPp190 expression is upregulated in a tbph-null fly
      model, providing evidence that this deregulation is associated to tbph silencing.
      Our results introduce RhoGAPp190 as a novel potential mediator in the complex
      scenario of events resulting from in vivo tbph loss-of-function.

PMID- 29652935
TI  - Adaptability of shallow subsurface drip irrigation of alfalfa in an arid desert
      area of Northern Xinjiang.
AB  - A suitable irrigation method adopted to arid desert conditions, including a
      special soil structure and specialized plants, has been continuously studied and
      improved. A field study was conducted in the Awei irrigation area of Aletai in
      Xinjiang in 2015 and 2016 to investigate the applicability of shallow subsurface
      drip irrigation (SSDI) in an arid desert area. A completely randomized block
      design with three replications and three treatments for drip tape subsurface
      depths at 5, 10, 20 cm was established. The results indicated that the vertical
      distribution of the soil moisture of subsurface drip irrigation (SDI, buried
      depth at 20 cm) was mainly concentrated at 0-60 cm, while SSDI (buried depth at 5
      and 10 cm) was concentrated at 0-30 cm. However, the roots distributions were
      concentrated at 0-30 cm for SDI and SSDI. The chlorophyll content and water
      consumption intensity for alfalfa first increased and then decreased in arid
      desert conditions. The dry yield and water use efficiency (WUE) of SSDI (buried
      depth at 10 cm) were higher than those of SDI. The SSDI was practical in arid
      desert conditions and the recommended buried depth was 10 cm.

PMID- 29652934
TI  - The quest for a non-vector psyllid: Natural variation in acquisition and
      transmission of the huanglongbing pathogen 'Candidatus Liberibacter asiaticus' by
      Asian citrus psyllid isofemale lines.
AB  - Genetic variability in insect vectors is valuable to study vector competence
      determinants and to select non-vector populations that may help reduce the spread
      of vector-borne pathogens. We collected and tested vector competency of 15
      isofemale lines of Asian citrus psyllid, Diaphorina citri, vector of 'Candidatus
      Liberibacter asiaticus' (CLas). CLas is associated with huanglongbing (citrus
      greening), the most serious citrus disease worldwide. D. citri adults were
      collected from orange jasmine (Murraya paniculata) hedges in Florida, and
      individual pairs (females and males) were caged on healthy Murraya plants for egg
      laying. The progeny from each pair that tested CLas-negative by qPCR were
      maintained on Murraya plants and considered an isofemale line. Six acquisition
      tests on D. citri adults that were reared as nymphs on CLas-infected citrus, from
      various generations of each line, were conducted to assess their acquisition
      rates (percentage of qPCR-positive adults). Three lines with mean acquisition
      rates of 28 to 32%, were classified as 'good' acquirers and three other lines
      were classified as 'poor' acquirers, with only 5 to 8% acquisition rates. All
      lines were further tested for their ability to inoculate CLas by confining CLas
      exposed psyllids for one week onto healthy citrus leaves (6-10 adults/leaf/week),
      and testing the leaves for CLas by qPCR. Mean inoculation rates were 19 to 28%
      for the three good acquirer lines and 0 to 3% for the three poor acquirer lines.
      Statistical analyses indicated positive correlations between CLas acquisition and
      inoculation rates, as well as between CLas titer in the psyllids and CLas
      acquisition or inoculation rates. Phenotypic and molecular characterization of
      one of the good and one of the poor acquirer lines revealed differences between
      them in color morphs and hemocyanin expression, but not the composition of
      bacterial endosymbionts. Understanding the genetic architecture of CLas
      transmission will enable the development of new tools for combating this
      devastating citrus disease.

PMID- 29652936
TI  - Does scale matter? A systematic review of incorporating biological realism when
      predicting changes in species distributions.
AB  - BACKGROUND: There is ample evidence that biotic factors, such as biotic
      interactions and dispersal capacity, can affect species distributions and
      influence species' responses to climate change. However, little is known about
      how these factors affect predictions from species distribution models (SDMs) with
      respect to spatial grain and extent of the models. OBJECTIVES: Understanding how
      spatial scale influences the effects of biological processes in SDMs is important
      because SDMs are one of the primary tools used by conservation biologists to
      assess biodiversity impacts of climate change. DATA SOURCES AND STUDY ELIGIBILITY
      CRITERIA: We systematically reviewed SDM studies published from 2003-2015 using
      ISI Web of Science searches to: (1) determine the current state and key knowledge
      gaps of SDMs that incorporate biotic interactions and dispersal; and (2)
      understand how choice of spatial scale may alter the influence of biological
      processes on SDM predictions. SYNTHESIS METHODS AND LIMITATIONS: We used linear
      mixed effects models to examine how predictions from SDMs changed in response to
      the effects of spatial scale, dispersal, and biotic interactions. RESULTS: There
      were important biases in studies including an emphasis on terrestrial ecosystems
      in northern latitudes and little representation of aquatic ecosystems. Our
      results suggest that neither spatial extent nor grain influence projected climate
      induced changes in species ranges when SDMs include dispersal or biotic
      interactions. CONCLUSIONS: We identified several knowledge gaps and suggest that
      SDM studies forecasting the effects of climate change should: 1) address broader
      ranges of taxa and locations; and 1) report the grain size, extent, and results
      with and without biological complexity. The spatial scale of analysis in SDMs did
      not affect estimates of projected range shifts with dispersal and biotic
      interactions. However, the lack of reporting on results with and without
      biological complexity precluded many studies from our analysis.

PMID- 29652937
TI  - Trajectories of maternal depressive symptoms during pregnancy and the first 12
      months postpartum and child externalizing and internalizing behavior at three
      years.
AB  - BACKGROUND: Most evidence of the association between maternal depression and
      children's development is limited by being cross-sectional. To date, few studies
      have modelled trajectories of maternal depressive symptoms from pregnancy through
      the early postpartum years and examined their association with social emotional
      and behavior functioning in preschool children. The objectives of this study were
      to: 1) identify distinct groups of women defined by their trajectories of
      depressive symptoms across four time points from mid-pregnancy to one year
      postpartum; and 2) examine the associations between these trajectories and child
      internalizing and externalizing behaviors. METHODS: We analyzed data from the All
      Our Families (AOF) study, a large, population based pregnancy cohort of mother
      child dyads in Alberta, Canada. The AOF study is an ongoing pregnancy cohort
      study designed to investigate relationships between the prenatal and early life
      period and outcomes for children and mothers. Maternal depressive symptoms were
      assessed using the Edinburgh Postnatal Depression Scale. Children's behavioral
      functioning at age 3 was assessed using the Behavior Scales developed for the
      Canadian National Longitudinal Survey of Children and Youth. Longitudinal latent
      class analysis was conducted to identify trajectories of women's depressive
      symptoms across four time points from pregnancy to 1 year postpartum. We used
      multivariable logistic regression to assess the relationship between trajectories
      of maternal depressive symptoms and children's behavior, while adjusting for
      other significant maternal, child and psychosocial factors. RESULTS: 1983
      participants met eligibility criteria. We identified four distinct trajectories
      of maternal depressive symptoms: low level (64.7%); early postpartum (10.9%);
      subclinical (18.8%); and persistent high (5.6%). In multivariable models, the
      proportion of children with elevated behavior symptoms was highest for children
      whose mothers had persistent high depressive symptoms, followed by mothers with
      moderate symptoms (early postpartum and subclinical trajectories) and lowest for
      minimal symptoms. After accounting for demographic, child and psychosocial
      factors, the relationships between depression trajectories and child
      hyperactivity/inattention, physical aggression (subclinical trajectory only) and
      separation anxiety symptoms remained significant. CONCLUSION: These findings
      suggest both externalizing and internalizing children's behaviors are associated
      with prolonged maternal depressive symptoms. There is a good case for the need to
      move beyond overly simplistic clinical cutoff approaches of depressed/not
      depressed in screening for perinatal depression. Women with elevated depressive
      symptoms at clinical and subclinical levels need to be identified, provided with
      evidence-based treatment, and monitored with repeat screening to improve maternal
      mental health outcomes and reduce the risk of associated negative outcomes on
      children's early social-emotional and behavior development.

PMID- 29652938
TI  - Cost of malaria treatment and health seeking behaviour of children under-five
      years in the Upper West Region of Ghana.
AB  - BACKGROUND: There is limited knowledge on cost of treating malaria in children
      under-five years in northern Ghana which poses a challenge in determining whether
      interventions such as the National Health Insurance Scheme (NHIS) and Community
      based Health Planning and Services (CHPS) have reduced the economic burden of
      malaria to households or not. This study examined the malaria care seeking and
      cost of treatment in children under-five years in the Upper West Region of Ghana.
      METHODS: The study used a cross-sectional, quantitative design and data were
      collected between July and August 2016 in three districts in the Upper West
      Region of Ghana. A total of 574 women who had under-five children were
      interviewed. Socio-demographic characteristics of respondents, malaria seeking
      patterns for under-five children with malaria as well as direct medical and non
      medical costs associated with treating under-five children with malaria were
      collected from the patient perspective. Analysis was performed using STATA 12.
      RESULTS: Out of 574 women visited, about 63% (360) had children who had malaria
      and sought treatment. Most treatment was done at formal health facilities such as
      the health centres (37%) and the CHPS (35%) while 3% had self-treatment at home.
      The main reason for choice of place of treatment outside home was nearness to
      home (53%). The average direct medical and non-medical costs associated with
      treating an under-five child with malaria were US$4.13 and US$3.04 respectively.
      The average cost on transportation alone was US$2.64. Overall, the average direct
      medical and non-medical cost associated with treating an under-five child with
      malaria was US$4.91(range: minimum = US$0.13 -maximum = US$46.75). Children who
      were enrolled into the NHIS paid an average amount of US$4.76 compared with
      US$5.88 for those not enrolled, though the difference was not statistically
      significant (p-value = 0.15). CONCLUSIONS: The average cost to households in
      treating an under-five child with malaria was US$4.91. This amount is
      considerably high given the poverty level in the area. Children not insured paid
      a little over one US dollar for malaria treatment compared to those insured.
      Efforts to improve enrolment into the NHIS may be needed to reduce the cost of
      malaria treatment to households. Construction of more health facilities near to
      community members and at hard to reach areas will improve access to health care
      and reduce direct non-medical cost such as transportation costs.

PMID- 29652939
TI  - Seeing for speaking: Semantic and lexical information provided by briefly
      presented, naturalistic action scenes.
AB  - At the interface between scene perception and speech production, we investigated
      how rapidly action scenes can activate semantic and lexical information.
      Experiment 1 examined how complex action-scene primes, presented for 150 ms, 100
      ms, or 50 ms and subsequently masked, influenced the speed with which immediately
      following action-picture targets are named. Prime and target actions were either
      identical, showed the same action with different actors and environments, or were
      unrelated. Relative to unrelated primes, identical and same-action primes
      facilitated naming the target action, even when presented for 50 ms. In
      Experiment 2, neutral primes assessed the direction of effects. Identical and
      same-action scenes induced facilitation but unrelated actions induced
      interference. In Experiment 3, written verbs were used as targets for naming,
      preceded by action primes. When target verbs denoted the prime action, clear
      facilitation was obtained. In contrast, interference was observed when target
      verbs were phonologically similar, but otherwise unrelated, to the names of prime
      actions. This is clear evidence for word-form activation by masked action scenes.
      Masked action pictures thus provide conceptual information that is detailed
      enough to facilitate apprehension and naming of immediately following scenes.
      Masked actions even activate their word-form information-as is evident when
      targets are words. We thus show how language production can be primed with
      briefly flashed masked action scenes, in answer to long-standing questions in
      scene processing.

PMID- 29652940
TI  - Functionality of cow milk naturally enriched with polyunsaturated fatty acids and
      polyphenols in diets for diabetic rats.
AB  - The increasing incidence of diabetes mellitus is becoming a serious threat to
      human health in various parts of the world. Studies with dairy products have
      shown a potential beneficial effect against diabetes. This experiment evaluated
      the supplementation of milk naturally enriched with polyunsaturated fatty acids
      (PUFA) and polyphenols in rats with streptozotocin-induced diabetes. Forty male
      28-day-old Wistar rats were distributed in four experimental treatments of
      diabetic animals (streptozotocin induction) and a normal group (non-induced).
      Experimental treatments were: control (water), whole common milk (COM-M), milk
      enriched with PUFA (PUFA-M), milk enriched with PUFA and polyphenols (PUFA/P-M)
      through a special diet offered to dairy cows. Milk supplementation at a dose 5
      mL/kg body weight was performed for 77 days, 42 days before and 35 days after
      diabetes induction. The COM-M supplementation increased brown fat deposits,
      reduced post-induction glucose levels, reduced blood fructosamine levels, and
      improved glucose tolerance. Milk enriched with PUFA reduced final fasting
      glucose, LDL levels, and improved blood antioxidant capacity. Milk enriched with
      PUFA and polyphenols promoted an increase in gastrocnemius muscle mass, and a
      reduction in mesenteric fat and LDL levels. Milk intake, with an emphasis on milk
      enriched with PUFA and polyphenols, attenuated the metabolic disorders of
      streptozotocin-induced diabetes in rats.

PMID- 29652941
TI  - Observed to expected or logistic regression to identify hospitals with high or
      low 30-day mortality?
AB  - INTRODUCTION: A common quality indicator for monitoring and comparing hospitals
      is based on death within 30 days of admission. An important use is to determine
      whether a hospital has higher or lower mortality than other hospitals. Thus, the
      ability to identify such outliers correctly is essential. Two approaches for
      detection are: 1) calculating the ratio of observed to expected number of deaths
      (OE) per hospital and 2) including all hospitals in a logistic regression (LR)
      comparing each hospital to a form of average over all hospitals. The aim of this
      study was to compare OE and LR with respect to correctly identifying 30-day
      mortality outliers. Modifications of the methods, i.e., variance corrected
      approach of OE (OE-Faris), bias corrected LR (LR-Firth), and trimmed mean
      variants of LR and LR-Firth were also studied. MATERIALS AND METHODS: To study
      the properties of OE and LR and their variants, we performed a simulation study
      by generating patient data from hospitals with known outlier status (low
      mortality, high mortality, non-outlier). Data from simulated scenarios with
      varying number of hospitals, hospital volume, and mortality outlier status, were
      analysed by the different methods and compared by level of significance (ability
      to falsely claim an outlier) and power (ability to reveal an outlier). Moreover,
      administrative data for patients with acute myocardial infarction (AMI), stroke,
      and hip fracture from Norwegian hospitals for 2012-2014 were analysed. RESULTS:
      None of the methods achieved the nominal (test) level of significance for both
      low and high mortality outliers. For low mortality outliers, the levels of
      significance were increased four- to fivefold for OE and OE-Faris. For high
      mortality outliers, OE and OE-Faris, LR 25% trimmed and LR-Firth 10% and 25%
      trimmed maintained approximately the nominal level. The methods agreed with
      respect to outlier status for 94.1% of the AMI hospitals, 98.0% of the stroke,
      and 97.8% of the hip fracture hospitals. CONCLUSION: We recommend, on the
      balance, LR-Firth 10% or 25% trimmed for detection of both low and high mortality
      outliers.

PMID- 29652942
TI  - Correction: Energy expenditure in caving.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0170853.].

PMID- 29652943
TI  - Correction: Human adipose derived stem cells regress fibrosis in a chronic renal
      fibrotic model induced by adenine.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0187907.].

PMID- 29652944
TI  - Epidemiology of sepsis in Brazil: Incidence, lethality, costs, and other
      indicators for Brazilian Unified Health System hospitalizations from 2006 to
      2015.
AB  - BACKGROUND: Sepsis is considered a major worldwide health burden, with high
      mortality and associated costs. Health indicators are essential to define
      strategies to improve the treatment of diseases, and the epidemiology information
      of sepsis in developing countries is scarce. Thus, the aim of this work is to
      assess trends in the incidence, lethality, costs, and other indicators of sepsis
      for Brazilian Unified Health System (SUS-Sistema Unico de Saude) hospitalizations
      for the period from January 2006 to December 2015. MATERIALS AND METHODS: We
      conducted this study using data from the SUS hospital information system. We
      selected registries of SUS hospitalizations of patients diagnosed with sepsis
      (total of 724,458 cases from 4,271 public and private Brazilian hospitals).
      RESULTS: From 2006 to 2015, the annual sepsis incidence increased 50.5% from
      31.5/100,000 to 47.4/100,000 persons. The mean hospital length of stay (LOS) was
      9.0 days. A total of 29.1% of the hospitalizations had admission to the intensive
      care unit (ICU) with a mean ICU LOS of 8.0 days. The mean cost per
      hospitalization was US$624.0 and for hospitalizations requiring intensive care
      was U$1,708.1. The overall sepsis lethality rate was 46.3%, and for
      hospitalizations with admission to the ICU, it was 64.5%. During the study
      period, the lethality rate for children/teenagers decreased 40.1%, but for all
      other age groups it increased 11.4%. The sepsis lethality rate in public
      hospitals (55.5%) was higher than private hospitals (37.0%) (p < 0.001). The mean
      hospitalization LOS for public hospitals (10.3 days) was higher than private
      hospitals (7.6 days) (p < 0.001). CONCLUSIONS: The incidence and lethality rate
      of sepsis increased in SUS hospitalizations during the study period. The SUS's
      low reimbursement to hospitals for treating sepsis may be one of the reasons for
      the high lethality rate.

PMID- 29652945
TI  - Clinical evaluation and validation of laboratory methods for the diagnosis of
      Bordetella pertussis infection: Culture, polymerase chain reaction (PCR) and anti
      pertussis toxin IgG serology (IgG-PT).
AB  - INTRODUCTION: The appropriate use of clinically accurate diagnostic tests is
      essential for the detection of pertussis, a poorly controlled vaccine-preventable
      disease. The purpose of this study was to estimate the sensitivity and
      specificity of different diagnostic criteria including culture, multi-target
      polymerase chain reaction (PCR), anti-pertussis toxin IgG (IgG-PT) serology, and
      the use of a clinical case definition. An additional objective was to describe
      the optimal timing of specimen collection for the various tests. METHODS:
      Clinical specimens were collected from patients with cough illness at seven
      locations across the United States between 2007 and 2011. Nasopharyngeal and
      blood specimens were collected from each patient during the enrollment visit.
      Patients who had been coughing for <= 2 weeks were asked to return in 2-4 weeks
      for collection of a second, convalescent blood specimen. Sensitivity and
      specificity of each diagnostic test were estimated using three methods-pertussis
      culture as the "gold standard," composite reference standard analysis (CRS), and
      latent class analysis (LCA). RESULTS: Overall, 868 patients were enrolled and
      13.6% were B. pertussis positive by at least one diagnostic test. In a sample of
      545 participants with non-missing data on all four diagnostic criteria, culture
      was 64.0% sensitive, PCR was 90.6% sensitive, and both were 100% specific by LCA.
      CRS and LCA methods increased the sensitivity estimates for convalescent serology
      and the clinical case definition over the culture-based estimates. Culture and
      PCR were most sensitive when performed during the first two weeks of cough;
      serology was optimally sensitive after the second week of cough. CONCLUSIONS:
      Timing of specimen collection in relation to onset of illness should be
      considered when ordering diagnostic tests for pertussis. Consideration should be
      given to including IgG-PT serology as a confirmatory test in the Council of State
      and Territorial Epidemiologists (CSTE) case definition for pertussis.

PMID- 29652946
TI  - [Impact of the Chilean Explicit Guaranties Health System (GES) on breast cancer
      treatment].
AB  - Background Breast cancer is the most common malignant tumor in women in the
      world. In 2005, it was incorporated to the Explicit Guaranties Health System
      (GES) in Chile. Aim To describe the demographic and clinical characteristics of
      breast cancer patients and to determine the effect of incorporating these women
      to GES. Material and Methods Medical records of 5,119 women with breast cancer
      aged 59 +/- 14 years, attended at six public hospitals between 2000 and 2010 were
      reviewed. Median follow up was 87 months (range 1-182). Mortality was assessed
      using death certificates obtained at the National Identification Registry.
      Results Sixty six percent of women were in stage I-II, 29% in stage III and 5% in
      stage IV. Surgery was performed in 4023/5119 cases (79%), adyuvant radiotherapy
      in 3627/4517 cases (80%), chemotherapy in 3,204/3,424 cases (94%) and hormone
      therapy in 1,695/2,375 cases (71%). Between 2000 and 2010, there was a
      significant increase in the proportion of cases in stage I, from 8% to 25%, (p <
      0.01). Overall survival (OS) increased 1% per year, since the beginning of GES
      system (p = 0.024). Five year OS was 75.1%. The figures for Stage I, II, III and
      IV were 93, 84, 62 and 27% respectively (p < 0.01). Patients without lymph node
      involvement and who were not triple negative, had a significantly better OS.
      Conclusions There was a significant increase in stage I cases, and a 1% per year
      OS improvement after GES system started, compared with the previous period.

PMID- 29652947
TI  - [Predictors of remission from major depressive disorder in secondary care].
AB  - Background The knowledge of predictive factors in depression should help to deal
      with the disease. Aim To assess potential predictors of remission of major
      depressive disorders (MDD) in secondary care and to propose a predictive model.
      Material and Methods A 12 month follow-up study was conducted in a sample of 112
      outpatients at three psychiatric care centers of Chile, with baseline and
      quarterly assessments. Demographic, psychosocial, clinical and treatment factors
      as potential predictors, were assessed. A clinical interview with the checklist
      of DSM-IV diagnostic criteria, the Hamilton Depression Scale and the List of
      Threatening Experiences and Multidimensional Scale of Perceived Social Support
      were applied. Results The number of stressful events, perceived social support,
      baseline depression scores, melancholic features, time prior to beginning
      treatment at the secondary level and psychotherapeutic sessions were included in
      the model as predictors of remission. Sex, age, number of previous depressive
      episodes, psychiatric comorbidity and medical comorbidity were not significantly
      related with remission. Conclusions This model allows to predict depression score
      at six months with 70% of accuracy and the score at 12 months with 72% of
      accuracy.

PMID- 29652948
TI  - [Psychoactive substances use and health-related quality of life among school age
      adolescents].
AB  - Background The use of psychoactive substances among adolescents is a major social
      and public health concern. Aim To analyze association of substance abuse and
      multiple drug use with health-related quality of life (HRQOL) in adolescents
      attending a high school in Valparaiso, Chile. Material and Methods Analytical
      cross-sectional study conducted in a sample of adolescents attending high school.
      HRQOL was assessed using KIDSCREEN-52 questionnaire and substance use was
      measured using the Global school-based student health survey. Participants had to
      complete online, self-administered, anonymous questionnaires. Multiple logistic
      regression analyses were conducted to calculate Odd ratios. Results A total of
      550 adolescents aged 16 +/- 1 years old completed the questionnaires. Thirty nine
      percent consumed alcohol during the last month, 31% smoked, 33% used marijuana
      and 33% admitted the use of multiple drugs. High-risk alcohol consumption was
      associated with a lower perception of psychological well-being, self-perception
      and school environment. This last dimension was affected in those who admitted
      marijuana use during the last month. Multiple drug use (three substances) was
      associated with a lower perception of physical and psychological well-being, self
      perception, relationship with parents, family life and school environment.
      Conclusions High-risk alcohol consumption and multiple drug use (three
      substances) have a negative impact on the HRQOL of school age adolescents.

PMID- 29652949
TI  - [Association of sedentariness and health promoting lifestyles in older adults].
AB  - Background Part of having healthy lifestyles should be a regular practice of
      physical activities. Aim To evaluate the association between the practice of
      physical activity and healthy lifestyles in older people. Material and Methods
      The Health-Promoting Lifestyle Profile survey was applied to 1688 older people
      living in the community, aged 72 +/- 7 years (61% women). This survey includes
      questions about regular physical activity. Results Twenty four percent of
      surveyed participants declared to practice physical activities at least three
      times per week, without gender differences. Sedentariness increased along with
      age. There was a negative association between low physical activity and healthy
      lifestyles (odds ratio (OR): 3.2 confidence intervals (CI): 2.3-4.5). There was
      also an association between sedentariness and low self-realization (OR 2.4 CI:
      1.8-3.3), low responsibility with health (OR 1.6 CI: 1.22.1), low concern about
      nutrition (OR 1.8 CI: 1.4-2.4), low stress management (OR 2.0 CI: 1.5-2.7) and
      low interpersonal support (OR 2.0 CI: 1.5-2.6). Conclusions Sedentariness is
      negatively associated with health promoting lifestyles in this group of older
      people.

PMID- 29652950
TI  - [Referral to rehabilitation services of patients discharged from a general
      hospital with a potentially disabling condition].
AB  - Background Patients discharged from general hospitals with a potentially
      disabling condition can benefit in their recovery with the aid of physical
      medicine and rehabilitation services. Aim To determine the proportion of patients
      discharged from a general hospital with a potentially disabling condition, who
      were derived to physiatry for rehabilitation. Material and Methods Review of the
      discharge database of a general hospital, identifying all discharges with a
      potentially disabling condition, and those who were effectively derived for
      rehabilitation. Results Only 7% of patients with a potentially disabling
      condition were effectively evaluated by Physiatry. Among these patients, 20% had
      neurological diseases and 19% had an amputation. Those attended by physiatry had
      a higher proportion of multidisciplinary care by the rehabilitation team.
      Conclusions A low proportion of patients discharged with a potentially disabling
      conditions are referred for an adequate rehabilitation therapy.

PMID- 29652951
TI  - [Characterization of Campylobacter jejuni samples coming form poultry meat and
      feces].
AB  - Background Campylobacter jejuni is one of the main causal agents of food borne
      diseases. Infections with this pathogen are mainly caused by chicken meat
      consumption. Aim To characterize antibiotic resistance and virulence factors in
      C. jejuni strains obtained from chicken meat and poultry feces in Central Chile.
      Material and Methods The presence of C. jejuni in 30 meat and 40 feces samples
      from poultry was studied. From these samples, we obtained 40 strains which were
      characterized at the molecular level for the presence of 16 genes involved in
      virulence using PCR. In parallel, antibiotic resistance for ciprofloxacin,
      nalidixic acid, tetracycline, erythromycin, azithromycin, chloramphenicol y
      ampicillin was analyzed. Results Twenty and 63% of feces and chicken meat samples
      were positive for C. jejuni, respectively. Moreover, a high percentage of strains
      showed antibiotic resistance, where 27% of strains were resistant to all tested
      antibiotics, except for azithromycin. Finally, 10% of the strains coming from
      feces contained 14 out of 16 virulence genes evaluated. Only 23% of the strains
      did not contain any of these genes. Conclusions A high percentage of feces and
      chicken meat samples are contaminated with C. jejuni. Moreover, these strains
      show a high genetic and phenotypic diversity represented by their antibiotic
      resistance profiles and the presence of virulence factors.

PMID- 29652952
TI  - [Carriage of Staphylococcus aureus among food service workers].
AB  - Background Staphylococcus aureus produces 11 serotypes of endotoxins that may
      cause food poisoning. Aim To determine the prevalence of type A enterotoxigenic
      Staphylococcus aureus carriage among food service workers in Chillan, Chile.
      Material and Methods Pharyngeal swabs were obtained from 100 food service workers
      and were cultured in Agar plates. After identifying the presence of
      Staphylococcus aureus, DNA was extracted to identify type A toxin by conventional
      PCR. Results Thirty eight percent of samples were colonized with Staphylococcus
      aureus. Among these, 26% were toxin A producers. Conclusions Half of the sampled
      workers carried Staphylococcus aureus and a quarter of these produced type A
      enterotoxin.

PMID- 29652953
TI  - [Prescription of opioids at the moment of discharge from an emergency
      department].
AB  - Background There is a worrisome increase in opioid prescription worldwide. Their
      use and overuse may cause adverse outcomes. Aim To determine incidence and
      characteristics of opioid prescription at discharge at an emergency department
      (ED). Material and Methods A prospective observational study in a random sample
      of adult patients attended at an ED of a teaching hospital. We reviewed medical
      records prescriptions for each patient to collect information about drugs
      prescribed, reason and medical indication of use (doses and duration). Results A
      total of 1,001 patients aged 50 +/- 20 years (61% women) were studied. Seven
      percent of patients received an opioid prescription at discharge from the ED,
      mainly to treat renal and back pain. The dose, duration of treatments or both
      were incompletely described in 54% of prescriptions. The dose of tramadol in
      drops was incomplete in 96% of prescriptions. Conclusions Seven percent of
      patients discharged from an ED received an opioid prescription, mainly to treat
      non-oncological acute pain. The lack of information detected in the prescriptions
      affected quality, safety and effectiveness of the treatment, especially when
      pharmaceutical formulations were drops.

PMID- 29652954
TI  - [Time to change the graduate-postgraduate liaison in Chilean medical education?
      Reflections about a double certification as Physician and Doctor in medical
      sciences].
AB  - In the last 150 years, scientific research has produced extraordinary discoveries
      in Medicine and there is no doubt that research will continue contributing
      substantially in the future but there is no the same conviction regarding how to
      provision such capacities in medical graduates. In Chile, the Faculties of
      Medicine created several doctorate programs in Medical Sciences (Ph.D.) to
      strengthen medical research. However, the low number of physicians who apply to
      these programs is a caveat. These programs provide the advanced third-cycle
      competencies expected by students aspiring for an excellence research
      certification and their incorporation into academia. Universities stand out in
      their capacity to adapt themselves to educational needs, developing programs
      designed to fill specific gaps. Ph.D. programs intercalated to the medical career
      show that this is the correct approach. The development of specific doctorate
      programs for the small number of physicians interested in research and for
      medical students with a strong interest in research could be an innovative
      solution to motivate and encourage them to develop a career in clinical
      investigation. Using this approach, Medical Schools and Doctorate in Medical
      Sciences programs would jointly stimulate the training of medical scientists.

PMID- 29652955
TI  - [Neurodevelopmental assessment of patients with congenital hypothyroidism].
AB  - Congenital hypothyroidism (CH) is the most common cause of preventable cognitive
      disability worldwide. Generally, it is produced by an alteration in the
      embryogenesis of the thyroid gland or by an alteration in the synthesis of
      thyroid hormones, which determine that affected patients have low or absent
      thyroid hormone concentrations. The importance of this fact is that brain
      development during the first three years of life is highly dependent on thyroid
      hormones. Prior to the implementation of national neonatal screening programs
      around the world, 8 to 27% of children with CH had an IQ lower than 70. Nowadays,
      this percentage is close to 0 in countries that have implemented the program. In
      Chile, CH neonatal screening program achieved national coverage in 1996.
      Currently, the incidence of the disease in our country is 1: 3163. The degree of
      disability produced by CH not only depends on the time of detection of the
      disease and the prompt start of therapy, but also on an adequate monitoring.
      Despite screening programs, neurocognitive impairment in schoolchildren and
      teenagers with CH is still observed, reflected in lower scores in cognitive,
      language and gross motor assessments, receptive communication, expressive
      communication, fine motor and gross motor skills compared to healthy children.
      Also, lesser achievements in learning and language disorders are observed. The
      objective of this review is to update the information available on
      neurodevelopment of patients with CH.

PMID- 29652956
TI  - [Tools for physical activity assessment in chronic obstructive pulmonary
      disease].
AB  - The prevalence and mortality of chronic obstructive pulmonary disease (COPD) is
      increasing in Chile, constituting a public health problem. Pulmonary and systemic
      consequences of COPD affect physical activity, as the disease progresses. There
      are multiple means for physical activity assessment, from low cost and easily
      applicable questionnaires to sophisticated laboratory tests. Physical inactivity
      is a modifiable risk factor for morbidity and mortality in patients with COPD.
      Physical activity interventions not only contribute to decrease the likelihood of
      mortality, but also protect from comorbidities, especially cardiovascular ones.
      It also plays a major role avoiding functional limitations of these subjects.
      Dyspnea and fatigue render exercise as an unpleasant activity for most patients
      with COPD. If psychological alterations such as anxiety and depression are
      summed, these patients drift towards an inactive lifestyle. This article analyzes
      several tools available to assess physical activity is patients with COPD, useful
      in clinical practice.

PMID- 29652957
TI  - [Impact of high salt consumption of blood pressure on a non-hypertensive
      population].
AB  - Background There is conflicting evidence regarding the role of salt intake in
      blood pressure (BP). Aim To estimate the impact of salt consumption on the BP
      level of a non-hypertensive population aged between 15 and 64 years. Material and
      Methods Analytical-observational study using data from the National Health Survey
      2009-2010. A BP cut-off point at 120/80 mmHg BP was considered to determine risk.
      Salt consumption was divided into four strata. The prevalence ratios (PR) were
      determined using the Poisson model with robust variance. The formulas of the
      studies of Dal Grande and Walter for the estimation of population attributable
      fraction (PAF) were used. Results The sample was constituted by 1,263 individuals
      and 24.3% had BP at risk. A statistically significant association was observed
      between high salt intake and risk BP with PR of 1.91 (95% confidence intervals
      (CI) 1.44-2.57) in the consumption stratum of 11 g / day and more. It was
      estimated that 4.7% (95% CI 4.2-5.2) of BP risk can be attributed to salt
      consumption, when controlling by age group, sex and educational level.
      Conclusions The 4.7% PAF is lower than the figure of 30% reported abroad.
      Interventions to reduce salt consumption in the entire population and the
      identification of risk groups are recommended.

PMID- 29652958
TI  - [HPV vaccine implementation in Chile: an appraisal from the social determinants
      of health model].
AB  - Cervical cancer is the fourth most common neoplasm in women worldwide and its
      incidence is associated with profound social inequities. In Chile, it is the
      second cause of death in women of reproductive age. The Chilean clinical
      guideline identifies the vaccine against Human Papillomavirus (HPV) as the main
      preventive measure. Since 2014, the Ministry of Health has implemented free
      immunization against HPV for girls and female adolescents. This article
      critically analyzes this public policy from the viewpoint of health equity, using
      as framework the Social Determinants of Health Model. Specifically, we address
      the structural determinants of income and gender, which act as material and
      social barriers for achieving immunization, affecting protection against cervical
      cancer. These barriers correspond to the high cost of the vaccine, and social
      attitudes/cultural beliefs towards sexual behavior in Latin America and Chile
      that affect the acceptability of vaccination. The Social Determinants of Health
      Model constitutes a useful tool for identifying health inequities and
      understanding public policy from an equity viewpoint that complements the
      biomedical and epidemiological understanding of disease. In this topic, the
      initiative aims to strengthen the idea of health as a human right and health
      promotion as an essential function of public health policy.

PMID- 29652959
TI  - [Useful tools and methods for literature retrieval in pubmed: step-by-step guide
      for physicians].
AB  - Developing skills to search the medical literature has potential benefits on
      patient care and allow physicians to better orient their efforts when answering
      daily clinical questions. The objective of this paper is to share useful tools
      for optimizing medical literature retrieval in MEDLINE using PubMed including
      MeSH terms, filters and connectors.

PMID- 29652960
TI  - [Semblance of Professor Ramon Ortuzar Escobar. Presented at XXXVII Internal
      Medicine Congress, 2016].

PMID- 29652961
TI  - [Severe leg edema associated with the use of dopaminergic drugs in Parkinson's
      disease. Report of one case].
AB  - The main adverse effects of dopaminergic drugs used in Parkinson's disease are
      hypotension, somnolence, hallucinations and impulse control disorder. Less common
      is leg edema. We report on a 68-year-old male receiving levodopa and pramipexole
      consulting for severe leg edema lasting two years, whose etiology was not
      ascertained with multiple lab tests. This edema subsided substantially when
      pramipexole was discontinued and the dose of levodopa was increased to treat
      motor symptoms.

PMID- 29652962
TI  - [Myasthenia gravis and its association with lymphoproliferative disorders: a case
      series].
AB  - Myasthenia gravis (MG) is a rare autoimmune disease of the neuromuscular
      junction. It is characterized by variable weakness and excessive fatigability of
      skeletal muscles. In the last few years, numerous reports have been published
      showing the association between autoimmune diseases, such as systemic
      erythematous lupus or rheumatoid arthritis, with lymphoid neoplasias. The
      association between MG and lymphoid neoplasia seems to be less frequent. To
      analyze this association we reviewed the MG patients in the Department of
      Neurology, Hospital Salvador of Santiago, Chile. During a three-year period we
      identified four patients who developed different lymphoproliferative disorders:
      two with B-cell lymphoma, one with chronic lymphocytic leukaemia and one
      plasmacytoma with an associated amyloidosis. The MG was generalized but mild, all
      cases classified as type IIa according to the definition proposed by the MG
      Foundation of America. The neoplasia appeared two to 36 years after the onset of
      MG. These cases provide additional evidence of the association between MG and
      lymphoproliferative disorders.

PMID- 29652963
TI  - [Physical inactivity in Chile: we must answer the global call].

PMID- 29652964
TI  - [Chile needs better statistics and greater coverage in screening for diabetic
      retinopathy].

PMID- 29652965
TI  - [The challenge of the Intercultural Health Model: From geographic coexistence to
      scientific dialogue].

PMID- 29652966
TI  - [Molecular basis of methicillin-resistance in Staphylococcus aureus].
AB  - Staphylococcus aureus isolates resistant to several antimicrobials have been
      gradually emerged since the beginning of the antibiotic era. Consequently, the
      first isolation of methicillin-resistant S. aureus occurred in 1960, which was
      described a few years later in Chile. Currently, S. aureus resistant to
      antistaphylococcal penicillins is endemic in Chilean hospitals and worldwide,
      being responsible for a high burden of morbidity and mortality. This resistance
      is mediated by the expression of a new transpeptidase, named PBP2a or PBP2',
      which possesses lower affinity for the beta-lactam antibiotics, allowing the
      synthesis of peptidoglycan even in presence of these antimicrobial agents. This
      new enzyme is encoded by the mecA gene, itself embedded in a chromosomal cassette
      displaying a genomic island structure, of which there are several types and
      subtypes. Methicillin resistance is mainly regulated by an induction mechanism
      activated in the presence of beta-lactams, through a membrane receptor and a
      repressor of the gene expression. Although mec-independent methicillin resistance
      mechanisms have been described, they are clearly infrequent.

PMID- 29652967
TI  - [Pharmacokinetics of posaconazol in the prophylaxis and treatment of invasive
      fungal infection in immunocompromised children in a pediatric hospital].
AB  - Background There is no consensus on the optimal dosage use of posaconazole (PSC)
      for invasive fungal infection (IFI) in pediatric patients and normally it is
      adjusted with drug levels (DLs) >= 0.7 MUg/ml and >= 1.25 MUg/ml for prophylaxis
      and treatment, respectively. Objective To describe the experience of monitoring
      DLs of PSC in immunocompromised pediatric patients with IFI and to determine if
      the recommended doses reach CP effective in prophylaxis (>= 0.7 MUg/mL) and
      treatment (>= 1.25 MUg/mL). Method A retrospective analysis in children who
      received PSC from January 2012 to October 2016, in the Oncology and Bone Marrow
      Transplant units at Hospital Calvo Mackenna was done Six patients with 78 DLs
      were reviewed (4 prophylaxis and 4 treatment). Median PSC dose was 12.5 and 18.8
      mg/kg/d for prophylaxis and treatment, resulting in mean DLs of 0.97 and 1.8
      MUg/mL respectively. In prophylaxis 40/67 (60%) were recorded with DLs >= 0.70
      MUg/mL receiving a median dose of 12.5 mg/kg/d. While for treatment: 5/11 (46%)
      presented DLs >= 1.25 MUg/mL, receiving a median dose of 18 mg/kg/d. Conclusion
      Our results are in line with the recommended for PSC dosage, but individualized
      monitoring is required to maintain adequate DLs.

PMID- 29652968
TI  - [Therapeutic monitoring of antimicrobial agents in pediatrics. Review based on
      Latin American experiences].
AB  - This review summarizes recommendations of therapeutic monitoring of three
      antimicrobials based in regional data: vancomycin, amikacin and voriconazole in
      pediatric population. Regional evidence agrees with international literature
      regarding the requirement of higher daily doses than 40 mg/kg/day of vancomycin,
      as well as with the possibility of use one daily doses of amikacin and to
      recommend higher doses of voriconazole compared to the initially recommended
      doses of 8 mg/kg/day. Local data on the pharmacokinetic/pharmacodynamic behavior
      of various antimicrobials in pediatrics are of great value for dosing adjustment
      in our pediatric population. More studies in therapeutic monitoring in the use of
      antimicrobials in pediatrics should be performed in order to allow the generation
      of adequate treatment guidelines for this age group.

PMID- 29652969
TI  - [Molecular characterization and antimicrobial susceptibility pattern of extended
      spectrum beta-lactamase-producing Escherichia coli as cause of community acquired
      urinary tract infection].
AB  - Background Community acquired urinary tract infections (CaUTI) caused by strains
      of extended-spectrum beta-lactamases (ESBL) - producing Escherichia coli, mainly
      by strains carrying the blaCTX-M-15 gene, is a growing phenomenon worldwide. Aim
      To determine the antibiotic susceptibility pattern of ESBL-producing E. coli as
      cause of CaUTI and to identify their molecular pattern. Methods A descriptive
      study was performed in the city of Oaxaca, Mexico, from where 288 strains of
      CaUTI-producing strains of E. coli in adults with possible UTI were isolated. The
      CLSI criteria was followed to determine the antimicrobial susceptibility
      patterns, and their molecular characterization was performed by using PCR.
      Results 31.3% of E. coli strains isolated in our population were ESBL producers,
      which presented higher levels of antibiotic resistance than those of non
      producers of these enzymes. 95.6% of the studied strains were carriers of the
      blaCTX-M gene. Conclusions One-third of the Ca-UTI caused by E. coli in our
      population are caused by ESBL-producing strains, which present high levels of
      resistance to the antibiotics widely used in our community. This situation
      considerably decreases the number of antibiotics available for an empiric
      treatment against these infections.

PMID- 29652970
TI  - [Congenital toxoplasmosis: Serology, PCR, parasite isolation and molecular
      characterization of Toxoplasma gondii].
AB  - BACKGROUND: Congenital toxoplasmosis diagnosis in the newborn is a very important
      issue due to the need for early treatment to prevent future sequels. Aim To
      compare available methods at the institution for the diagnosis of congenital
      toxoplasmosis. Material and Methods In this study we have evaluated the different
      diagnostic tests used in 67 congenital exposed newborns, including serological
      tests, PCR, parasite isolation and molecular characterization. Results The ISAGA
      IgM and IgA tests showed sensitivity (Se) of 87 and 91%, respectively, and
      specificity (Sp) of 100%. When ISAGA IgM and IgA were performed simultaneously,
      the Se increased to 98% and the Sp was 100%. The presence of IgE contributed to
      the diagnosis when it was detected in the child's serum but not in maternal
      blood. In four congenital infected children the parasite was isolated and
      genotyped: one was genotype II and the other three were "atypical" genotypes. No
      parasite was isolated in children without congenital toxoplasmosis. Discussion
      Overall, serological tests showed a good diagnostic performance although in one
      case they were all negative and isolation was the only tool to identify the
      infection. We conclude that it is essential to use all diagnostic tests in every
      single exposed child, including if possible, molecular characterization due to
      its epidemiological implication.

PMID- 29652971
TI  - [Factors associated to survival in patients with HIV-TB in the Department of
      Infectious Diseases of the Arzobispo Loayza National Hospital, Peru, since 2004
      to 2012].
AB  - Background The main cause of death in HIV patients is tuberculosis (TB). However,
      few Latin American studies have evaluated the prognosis of patients with
      coinfection. Aim To determine the factors associated with survival in patients
      with HIV-TB coinfection treated at a Peruvian referral hospital. Methods A
      retrospective cohort study was performed based on clinical records of patients
      treated at the Department of Infectious Diseases in the Arzobispo Loayza National
      Hospital from 2004 to 2012. Survival was assessed using the Kaplan-Meier
      estimator and Cox Proportional Hazard Model. Results From 315 patients, 82 died
      during the follow-up. The mean of follow for each patient was 730 days. The
      multivariate analysis showed that receiving HAART (HR: 0,31; IC: 0,20-0,50; p <
      0,01) and having more weight (HR: 0,96; IC 0,94-0,98; p < 0,01) when the
      coinfection was diagnosed, were protective factors; while having a pathology
      different from TB (HR: 1,88; IC: 1,19-2,98; p < 0,01), age in years (HR: 1,76;
      IC: 1,12-2,74; p <= 0,01) and being hospitalized when diagnosed with TB (HR:
      1,69; IC 1,02-2,80; p < 0,04) were associated with lower survival. Discussion
      Receiving HAART and having more weight when the coinfection is diagnosed were
      associated with a higher chance of survival.

PMID- 29652972
TI  - [Genetic analysis of the mutations in HIV-1 infected population in Ecuador].
AB  - Background The international recommendations of antiretroviral treatment include
      resistance tests to guide the treatment regimen in each patient, which is not
      available on a regular basis in Ecuador. Aim To describe mutations that confer
      resistance to antiretrovirals in a population of Ecuadorian patients. Methods
      Plasma samples from 101 HIV-1 patients with failure to antiretroviral therapy,
      divided into 15 children and 86 adults, were studied with the GS Junior (Roche)
      and the sequences were analyzed with the DeepChek program. Results The most
      frequent mutations were M184V/I, K101E/P/H, K103N/S, D30N, M46L/I, I54L/M,
      V82T/F/A/S/L and L90M in adults and F77L, K103N/S, M46L/I, V82T/F/A/S/L and L90M
      in children. High resistance to non-nucleoside reverse transcriptase (RT)
      inhibitors in minority viral populations of adults and children (34.9% and 70%)
      was detected; in children both viral populations (majority and minority viral
      populations) (> 45%) were protease inhibitor resistant. Patients who had a
      greater number of therapeutic regimens had higher levels of resistance to
      antiretrovirals. Most of the samples were subtype B in the TR and protease
      region, and CRF25_cpx in integrase. Conclusions Mutations and resistance to
      antiretrovirals are shown in a population of Ecuadorian patients with HIV-1.
      These results will make it possible to issue a warning to health authorities
      about the need for resistance studies.

PMID- 29652973
TI  - [Febrile neutropenia in cancer patients: management in the emergency room].
AB  - Febrile neutropenia is a life-threatening condition that requires immediate
      attention, especially in patients with chemotherapy-related neutropenia. Patients
      with febrile neutropenia have a much greater risk of developing bacterial
      disease, and fever may be the only indicator of severe bacterial infection.
      Adequate management of febrile neutropenia emphasizes early recognition of
      patients, risk stratification, and antibiotic therapy administration during the
      first 60 minutes of admission to an emergency room. Not all children with febrile
      neutropenia carry the same risk of morbidity and mortality, so in recent years,
      efforts have been made to distinguish between high-risk patients where more
      aggressive hospital management is required. In children classified as low-risk,
      outpatient management may be considered initially or after 72 hours, whilst high
      risk patients should be hospitalized and managed with parenteral antibiotics.

PMID- 29652974
TI  - ?

PMID- 29652975
TI  - [A remarkable semantic convergence: infection and miasma].
AB  - The historical development of the terms "infection" and "miasma" is analyzed.
      Miasma was understood as a kind of corrupt or pestilent air that emanated from
      putrefactive bodies and spread infectious diseases. This concept was the dominant
      one to understand the cause of infectious diseases from antiquity to the dawn of
      the microbial theory. The concept of infection initially had a similar meaning to
      miasma, but is currently defined as the invasion of a host by an infectious
      agent. It will be discussed in this paper that both terms derive from the same
      original concept.

PMID- 29652976
TI  - [Escherichia vulneris etiologic agent of septic arthritis in a child].
AB  - Escherichia vulneris is a gram-negative bacillus that belongs to the family
      Enterobacteriaceae, with a questioned pathogenic role. However, it has been
      confirmed as the cause of wound infections. We report the case of a 12-year-old
      girl, previously healthy, with a diagnosis of septic arthritis of the right knee,
      secondary to a spinal lesion. Escherichia vulneris, an unusual etiology of septic
      arthritis in children, was isolated in the joint fluid. This case is one of the
      first cases of septic arthritis due to E. vulneris, secondary to a plant-derived
      foreign body in a child, described in the medical literature. The importance of
      performing the microbiological study of joint fluid in patients with septic
      arthritis caused by a foreign body of plant-derived origin is emphasized.

PMID- 29652977
TI  - [Auricular sporotrichosis. Atypical case report simulating bacterial cellulitis].
AB  - Sporotrichosis is the most common subcutaneous or implantation mycosis in Mexico.
      The case of a preauricular cutaneous-fixed sporotrichosis simulating atypical
      bacterial cellulitis is reported in an elderly patient with no history of trauma.
      The biopsy showed a suppurative granuloma with scarce yeast. Sporothrix schenckii
      was identified in the culture and confirmed by molecular biology. She was treated
      with itraconazole and a clinical and mycological cure was obtained. The case of
      atypical presentation is presented, coming from a semi-arid zone with extreme
      weather.

PMID- 29652978
TI  - [Importance of cleaning and disinfection of critical surfaces in dental health
      services. Impact of an intervention program].
AB  - Introduction Dental care has become a challenge for healthcare associated
      infection prevention programs, since the environment, within other factors, plays
      an important role in the transmission chain. Materials and Methods An
      intervention program was designed for the Dental Unit of Hospital Militar de
      Santiago, between years 2014 and 2015. The program contemplated 3 stages:
      diagnostic, intervention and evaluation stage. Objective To improve the safety of
      critical surfaces involved in dental healthcare. Results During the diagnostic
      stage, the cleaning and disinfection process was found to be deficient. The most
      contaminated critical surface was the instrument holder unit, then the clean area
      and lamp handle. The surfaces that significantly reduced their contamination,
      after the intervention, were the clean area and the instrument carrier unit.
      Conclusion Training in the processes of cleaning and disinfecting surfaces and
      dental equipment is one of the cost-effective strategies in preventing healthcare
      associated infections (HCAI), with simple and easy-to-apply methods.

PMID- 29652979
TI  - ?

PMID- 29652980
TI  - [Antibiotic stewardship in the newborn surgical patient].

PMID- 29652981
TI  - [Metabolic syndrome in HIV patients: an opportunity for nutritional
      supplementation?]

PMID- 29652982
TI  - [Identification of a HPGD mutation in three families affected with primary
      hypertrophic osteoarthropathy].
AB  - OBJECTIVE: To detect mutation of HPGD gene among three pedigrees affected with
      primary hypertrophic osteoarthropathy (PHO) by DNA sequencing and high-resolution
      melting (HRM) analysis. METHODS: Genomic DNA was extracted from peripheral blood
      samples collected from the pedigrees. PCR and direct sequencing were carried out
      to identify potential mutations of the HPGD gene. Amplicons containing the
      mutation spot were generated by nested PCR. The products were then subjected to
      HRM analysis using the HR-1 instrument. Direct sequencing was carried out in
      family members and healthy individuals to confirm the result of HRM analysis.
      RESULTS: A homozygous mutation c.310_311delCT was detected in 2 affected
      probands, while a heterozygous mutation c.310_311delCT was detected in the third
      proband. HRM analysis of the fragments encompassing HPGD exon 3 showed 3 curve
      patterns representing three different genotypes, i.e., the wild type, the
      c.310_311delCT homozygote, and the c.310_311delCT heterozygote. Result of DNA
      sequencing was consistent with that of the HRM analysis and phenotype of the
      subjects. CONCLUSION: The c.310_311delCT mutation may be the most prevalent
      mutation among Chinese population. HRM analysis has provided an optimized method
      for genetic testing of HPGD mutation for its simplicity, rapid turnover and high
      sensitivity.

PMID- 29652983
TI  - [Knocking-out of HIF1alpha gene by CRISPR/cas9 inhibits proliferation and
      invasiveness of prostate cancer DU145 cells].
AB  - OBJECTIVE: To explore the role of HIF1alpha gene in prostate cancer cell line
      DU145 by knocking it out with a novel gene-editing tool CRISPR/cas9 system.
      METHODS: A CRISPR/cas9 system with two sgRNAs targeting exon 1 of the HIF1alpha
      gene was constructed for the knock out experiment. CCK8 assay and transwell
      experiment were carried out to assess the effect of the knock out on the
      proliferation, migration and invasiveness of DU145 cells. RESULTS: The efficiency
      of gene-targeting was measured through a T7E1 assaying and sequence analysis,
      which confirmed that the partial knock out was successful and has led to a
      significant decrease in the expression of HIF1alpha and inhibition of cell
      proliferation, migration and invasiveness. CONCLUSION: A CRISPR/cas9 system for
      the knock out of HIF1alpha has been successfully constructed, which could inhibit
      the proliferation and migration of DU145 cells. The system can facilitate further
      studies of the HIF1alpha gene and its roles in tumorigenesis.

PMID- 29652984
TI  - [Analysis of disease-causing gene mutation in three Chinese families with
      congenital inherited cataract].
AB  - OBJECTIVE: To identify the disease-causing gene mutations in three Chinese
      pedigrees affected with congenital inherited cataract, in ordre to provide
      genetic counseling and prenatal diagnosis. METHODS: Using exons combined target
      region capture sequencing chip to screen the candidate disease-causing mutations,
      Sanger sequencing was used to confirm the disease-causing mutations. RESULTS:
      Family 1 was polymorphic cataract, family 2 was cerulean cataract, family 3 was
      coralliform cataract. The inheritance mode of the three pedigrees consisted with
      autosomal dominant inheritance. In family 1, a nonsense mutation of CRYbetaB2
      gene c.463C>T in exon 6 result in a p.Q155X amino acid change. In family 2, a
      missense mutation of of CRYGD gene c.43C>T in exon 2 result in a p.R14C amino
      acid change. In family 3, a missense mutation of CRYGD gene c.70C>A in exon 2
      result in a p.P23T amino aid change. No above-mentioned mutations were found in
      normal individuals. CONCLUSION: The nonsense mutation c.463C>T (p.Q155X) of
      CRYbetaB2 gene, the heterozygous mutations c.43C>T(p.R14C) of CRYGD gene and
      c.70C>A( p.P23T) of CRYGD gene was the disease-causing gene mutation in family 1,
      2 and 3 respectively, our results provid genetic counseling and prenatal
      diagnosis for these three families.

PMID- 29652985
TI  - [Mutation analysis and prenatal diagnosis for 50 pedigrees affected with
      Duchenne/Becker muscular dystrophy].
AB  - OBJECTIVE: To establish individualized prenatal diagnosis program for families
      affected with Duchenne/Becker muscular dystrophy (DMD/BMD) and different clinical
      background using a variety of methods. METHODS: Multiplex ligation-dependent
      probe amplification (MLPA) was performed on 50 patients suspected for DMD/BMD.
      For single exon deletions of the DMD gene, PCR was used for validating the
      results. For those without any deletion or duplication, Sanger sequencing was
      used to screen for DMD gene mutations in the children and their mothers. Prenatal
      genetic testing was provided to female carriers using chorionic villus,
      amniocentesis or cord blood samples. To ensure the accuracy of diagnosis, all
      prenatal specimens were also subjected to linkage analysis. RESULTS: Among the 50
      patients with DMD/BMD, 23 harbored large deletions, 11 only had single exon
      deletions, 10 harbored duplications, and 5 had small scare mutations. No mutation
      was detected in one family. For 37 women undergoing prenatal diagnosis, 10
      fetuses were identified as affected males, 6 were female carriers, while 21 were
      not found to carry any mutation. Testing of creatine kinase was consistent with
      the results of prenatal diagnosis. For a patient harboring exon 51 deletion, the
      same mutation was found in a fetus but not in their mother. The proband and fetus
      had inherited the same haplotype, which suggested that the mother probably has
      germline mosaicism for the mutation. CONCLUSION: Application of individualized
      methods for analyzing pregnant women with different clinical background can
      minimize the risk for giving birth to further children affected with DMD/BMD.

PMID- 29652986
TI  - [Clinical and genetic analysis of three pedigrees affected with myotonic
      dystrophy].
AB  - OBJECTIVE: To carry out clinical and genetic analysis for three pedigrees
      affected with myotonic dystrophy type 1 (DM1). METHODS: Three probands with
      clinically diagnosed DM and their familial members were recruited. Clinical data
      of the patients including clinical manifestations, electrocardiogram (ECG), and
      electromyogram (EEG) was collected. RESULTS: The clinical symptoms of all
      probands have progressed slowly and included myotonia, muscle weakness and muscle
      atrophy as the main manifestations. Disorders of other systems have included
      cataract, arrhythmia, alopecia, sexual dysfunction, and cognitive impairment. The
      EEG of the probands showed characteristic myotonia discharges. Genetic analysis
      revealed over 50 CTG repeats at the 3' end of the DMPK gene in all three
      probands. CONCLUSION: DM1 is a complex hereditary disorder involving multiple
      systems and overlaps with other diseases. In addition to clinical symptoms and
      EEG, genetic testing can facilitate its diagnosis at early stages.

PMID- 29652987
TI  - [Analysis of a pedigree affected with congenital hypofibrinogenemia due to
      heterozygous Ser313Ile mutation of fibrinogen gamma chain gene].
AB  - OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with
      congenital hypofibrinogenamia. METHODS: Peripheral blood samples were collected
      from 9 members from the pedigree. Routine coagulation tests including activated
      partial thromboplastin time (APTT), thrombin time (TT), the prothrombin time (PT)
      were carried out. The activity of fibrinogen (Fg: C) was measured using Clauss
      method, and fibrinogen antigen (Fg: Ag) was measured with immunoturbidimetry. All
      exons and exon-intron boundaries of the fibrinogen Aalpha, Bbeta and gamma chain
      genes were amplified using PCR, which was followed by direct sequencing.
      Suspected mutation was confirmed by reverse sequencing. The mutant fibrinogen was
      analyzed with Swiss-PdbViewer. RESULTS: The proband showed prolonged APTT, PT and
      TT. Her functional fibrinogen (Fg: C) and antigen fibrinogen (Fg: Ag) levels were
      reduced to 0.69 g/L and 0.72 g/L, respectively. Her mother and grandmother also
      had a low levels of fibrinogen, which were 0.99 g/L and 0.83 g/L for Fg: C, 1.02
      g/L and 0.87 g/L for Fg: Ag, respectively. The results of other members from the
      pedigree were all within the normal range. Genetic analysis reveled a
      heterozygous G>T mutation at nucleotide 7590 in exon 8 of gamma gene in the
      proband, which was predicted to be a novel Ser313Ile mutation. The mutation was
      also found in her mother and grandmother. Model analysis showed that the
      Ser313Ile mutation disturbed the hydrogen bonds between Ser313, Asn319 and
      Asp320. Moreover, the mutation also altered the mutual electrostatic force and
      affected the folding and instability of the mutant fibrinogen. CONCLUSION: The
      heterozygous Ser313Ile mutation probably underlies the hypofibrinogenemia in this
      pedigree.

PMID- 29652988
TI  - [Genetic and prenatal diagnosis of a retinitis pigmentosa pedigree].
AB  - OBJECTIVE: To explore the genetic etiology of a pedigree affected with hereditary
      retinitis pigmentosa. METHODS: High-throughput DNA sequencing was used to analyze
      the sequences of 173 genes associated with hereditary eye diseases in the
      proband. Suspected mutation was verified with PCR amplification and Sanger
      sequencing. RESULTS: The proband was found to have carried a c.570_571 ins
      GAAGATGCTGT insertional mutation in the RP2 gene located on the X chromosome. All
      female carriers of the pedigree were heterozygous, while all affected males were
      hemizygous for the same mutation. CONCLUSION: The inheritance pattern of this
      retinitis pigmentosa pedigree was X-linked recessive. The c.570_571 ins
      GAAGATGCTGT insertional mutation of the RP2 gene probably underlies the disease.

PMID- 29652989
TI  - [Analysis of clinical characteristics and genetic mutation in a pedigree affected
      with Chediak-Higashi syndrome].
AB  - OBJECTIVE: To explore the genetic basis for a pedigree affected with Chediak
      Higashi syndrome (CHS). METHODS: Clinical data of two CHS patients from the
      pedigree was collected and analyzed. Targeted next generation sequencing and
      Sanger sequencing were conducted to detect potential mutation of the LYST gene.
      RESULTS: Both patients presented immunodeficiency, oculocutaneous albinism, and
      acidophilic inclusion body on bone marrow and blood smears. A homozygous
      c.6077_6078insA (p.Tyr2026Terfs) mutation was detected in the LYST gene in both
      patients. CONCLUSION: Genetic testing can play an important role in the diagnosis
      of CHS.

PMID- 29652990
TI  - [Analysis of pathological mutation in a Chinese pedigree affected with familial
      exudative vitreoretinopathy].
AB  - OBJECTIVE: To detect potential mutation in a Chinese pedigree affected with
      familial exudative vitreoretinopathy (FEVR). METHODS: Clinical data of the
      pedigree was collected. Coding regions of candidate genes were amplified by PCR
      and subjected to next generation sequencing (NGS). Suspected mutations were
      verified by Sanger sequencing and segregation analysis. RESULTS: Two novel
      heterozygous mutations (c.1695dupC and c.552-563del) were respectively detected
      in the LRP5 and ZNF408 genes in the proband. Both mutations were inherited from
      the affected mother. By Sanger sequencing, the c.552-563del mutation was also
      detected among unaffected members, while the c.1695dupC mutation was only
      detected in affected members from the pedigree and was not recorded by the HGMD,
      NCBI, or 1000 genome database. Upon prenatal diagnosis, the fetus was found to
      carry the same mutations. CONCLUSION: Combined NGS and Sanger sequencing not only
      can reduce the time required for diagnosis but also enable accurate prenatal
      diagnosis for FEVR.

PMID- 29652991
TI  - [Genetic analysis of a family affected with pulmonary hypertension secondary to
      hereditary hemorrhagic telangiectasia].
AB  - OBJECTIVE: To carry out genetic testing for a family affected with pulmonary
      hypertension (PH) as the initial sign of hereditary hemorrhagic telangiectasia
      (HHT). METHODS: High throughput sequencing was performed to detect potential
      mutation in the coding regions of endoglin (ENG), activin receptor-like kinase 1
      (ACVRL1) and mothers against decapentaplegic homolog 4 (SMAD4) genes. RESULTS: A
      pathogenic heterozygous c.814C>T (p.Gln272Ter) mutation of the ACVRL1 gene was
      identified in the proband. Her mother and two sons have carried the same
      mutation. CONCLUSION: The c.814C>T (p.Gln272Ter) mutation of the ACVRL1 gene
      probably underlies the disease in this family. Genetic testing should be
      recommended to HHT patient, in particular those with pulmonary hypertension.

PMID- 29652992
TI  - [Phenotypic and mutational analysis of a pedigree affected with hereditary
      coagulation factor V deficiency].
AB  - OBJECTIVE: To explore the molecular pathogenesis for a pedigree affected with
      coagulation factor V (FV) deficiency. METHODS: Prothrombin time (PT), activated
      partial thromboplastin time (APTT), fibrinogen (FIB), coagulation factor II
      activity (FII: C), FV activity (FV: C), coagulation factor VII activity (FVII:
      C), and coagulation factor X activity (FX: C) were determined with a STAGO
      automatic coagulometer. FV antigen (FV: Ag) was detected with enzyme linked
      immunosorbent assay (ELISA). All exons and their flanking regions, and 5' and 3'
      untranslated regions of the F5 gene were analyzed by direct sequencing. Suspected
      mutation was verified by reverse sequencing as well as testing of family members.
      ClustalX software was used to analyze the conservative property of the mutation
      sites. PROVEAN and MutationTaster online software was used to predict the effect
      of the mutation on the protein function. Swiss-pdbViewer was used to analyze the
      protein model and interaction of amino acids. RESULTS: The PT and APTT of the
      proband were slightly prolonged to 15.2 s and 41.8 s, respectively. And the FV: C
      and FV: Ag measured 55% and 62%, respectively. The FV: C and FV: Ag of his father
      and son were decreased to various extent (60%, 65% and 31%, 40%, respectively). A
      c.911G>A heterozygous mutation (Gly276Glu) was detected in exon 6 of the proband,
      for which her father and son were heterozygotes. The same mutation was not found
      in her mother, brother and husband. Conservation analysis showed that the Gly276
      is highly conserved across various species. By bioinformatic analysis, the
      PROVEAN (scored -6.214) indicated Gly276Glu was harmful, and MutationTaster
      (scored 0.976) suggested that it is pathogenic. Model analysis suggested there
      are two hydrogen bonds between Gly276 and Ile298 in the wild type protein. When
      Gly276 was replaced by Glu276, the original hydrogen bond did not change, but the
      side chain of Glu was extended, which added steric hindrance with the surrounding
      amino acids, which resulted in decreased protein stability. CONCLUSION: The
      heterozygous c.911G>A (Gly276Glu) mutation of the F5 gene probably underlies the
      decreased level of FVin the proband.

PMID- 29652993
TI  - [Analysis of WAS gene mutation in a Chinese family affected with Wiskott-Aldrich
      syndrome].
AB  - OBJECTIVE: To detect potential mutation of the WAS gene in a Chinese family
      affected with Wiskott-Aldrich syndrome. METHODS: Peripheral blood samples were
      collected from the proband and his family members. All exons and flanking regions
      of the WAS gene were subjected to PCR amplification - Sanger sequencing as well
      as restriction endonuclease analysis. Plasma level of B-cell activating factor
      (BAFF) was also determined for all family members. RESULTS: A hemizygous mutation
      (c.257G>A) of the WAS gene was identified in all patients from the family, for
      which the patient's mother was heterozygous. The same mutation was not found
      among healthy members of the family. Compared with unaffected members, all
      patients had a higher level of BAFF. CONCLUSION: The c.257G>A mutation of the WAS
      gene probably underlies the Wiskott-Aldrich syndrome in this family.

PMID- 29652994
TI  - [Association of OSMR gene polymorphisms with dilated cardiomyopathy in a Han
      Chinese population].
AB  - OBJECTIVE: To assess the association of polymorphisms of oncostatin M receptor
      (OSMR) gene with dilated cardiomyopathy (DCM) in a Han Chinese population.
      METHODS: For 351 DCM patients and 418 healthy controls, two single nucleotide
      polymorphisms (SNPs) of the OSMR gene, namely rs2292016 (promoter, -100G/T) and
      rs2278329 (missense, Asp553Asn), were genotyped with a TaqMan SNP genotyping
      assay. Two hundred of the patients were also followed up for (49.85 +/- 22.52)
      months. RESULTS: For rs2292016, carriers of GT genotype were more likely to
      develop DCM compared to those with GG and TT genotypes (OR=1.45, 95%CI: 1.09
      1.92, P=0.01). For those who did not receive cardiac resynchronization therapy,
      the GG genotype of rs2292016 was an independent indicator for poor prognosis
      (OR=1.69, 95%CI: 1.11-2.63, P=0.017). No association was found between genotypes
      of rs2278329 with the susceptibility or prognosis of DCM. CONCLUSION:
      Polymorphisms of the OSMR rs2292016 locus are related to the development and
      outcome of DCM.

PMID- 29652995
TI  - [Association of polymorphisms of NAPE-PLD and FAAH genes with schizophrenia in
      Chinese Han population].
AB  - OBJECTIVE: To assess the association of polymorphisms of N-acyl
      phosphatidylethanolamine-phospholipase D (DAPE-PLD) and fatty acid amide
      hydrolase (FAAH) genes, as well as their interaction, with schizophrenia.
      METHODS: Polymorphisms of NAPE-PLD rs12540583 and FAAH rs324420, rs2295633, and
      rs6429600 were determined with PCR - restriction fragment length polymorphism
      assay and Sanger sequencing. The genotypes of 345 subjects of Han Chinese origin
      diagnosed with schizophrenia and a 403 controls were compared. The results were
      analyzed with SPSS 17.0, and the interaction of the two genes was analyzed using
      a multifactor dimensionality reduction (MDR) method. RESULTS: The frequency of
      NAPE-PLD rs12540583 polymorphism was significantly different between the two
      groups under both dominant and additive models (chi2=17.18 vs. chi2=18.94,
      P<0.0125). The frequencies of AC genotype and C allele of the patient group at
      rs12540583 were higher than those of the controls, and the interaction of NAPE
      PLD and FAAH was associated with schizophrenia. A four-loci model (rs12540583,
      rs324420, rs2295633 and rs6429600) can best model the interaction between NAPE
      PLD and FAAH. CONCLUSION: The AC genotype and C allele of NAPE-PLD rs12540583
      locus are risk factors for schizophrenia, and the interaction between NAPE-PLD
      rs12540583 and FAAH rs324420, rs2295633 and rs6429600 is associated with
      schizophrenia.

PMID- 29652996
TI  - [Association of programmed cell death 1 (PDCD1) gene polymorphisms with
      colorectal cancer among Han Chinese population].
AB  - OBJECTIVE: To assess the association of programmed cell death 1 (PDCD1) gene
      polymorphisms with the susceptibility and/or progression of colorectal cancer.
      METHODS: A hospital-based case-control study was carried out, which recruited 426
      colorectal cancer patients and 500 healthy individuals. Five single nucleotide
      polymorphisms, namely rs36084323, rs11568821, rs2227981, rs2227982 and
      rs10204525, were selected for the study and genotyped with a polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) assay. RESULTS: The
      G allele of rs36084323 under a dominant model was associated with increased risk
      of advanced TNM staging of colorectal cancer progression (OR=1.59, 95%CI=1.02
      2.48). Haplotypes G-G-C-T-A and A-G-C-C-G of the rs36084323, rs11568821,
      rs2227981, rs2227982, and rs10204525 were negatively associated with the
      occurrence of colorectal cancer. CONCLUSION: The G allele of rs36084323 is
      associated with increased risk of advanced TNM staging of colorectal cancer.
      Conversely, the incidence of colorectal cancer is negatively associated with the
      haplotypes G-G-C-T-A and A-G-C-C-G of rs36084323, rs11568821, rs2227981,
      rs2227982, and rs10204525.

PMID- 29652997
TI  - [Application of droplet digital PCR for non-invasive prenatal diagnosis of single
      gene disease in two families].
AB  - OBJECTIVE: To assess the value of droplet digital PCR (ddPCR) for non-invasive
      prenatal diagnosis of single gene disease in two families. METHODS: Paternal
      mutation in cell-free DNA derived from the maternal blood and amniotic fluid DNA
      was detected by ddPCR. Suspected mutation in the amniotic fluid DNA was verified
      with Sanger sequencing. RESULTS: The result of ddPCR and Sanger sequencing
      indicated that the fetuses have carried pathogenic mutations from the paternal
      side in both families. CONCLUSION: Droplet digital PCR can accurately detect
      paternal mutation carried by the fetus, and it is sensitive and reliable for
      analyzing trace samples. This method may be applied for the diagnosis of single
      gene diseases caused by paternal mutation using peripheral blood sample derived
      from the mother.

PMID- 29652998
TI  - [Application of quantitative fluorescencet-PCR in the prenatal diagnosis of
      chromosomale aneuploidies].
AB  - OBJECTIVE: To assess the accuracy of quantitative fluorescence PCR(QF-PCR) for
      the detection of fetal chromosomal aneuploidies and its values for prenatal
      diagnosis. METHODS: QF-PCR and chromosomal karyotyping were used to analyze 6066
      amniotic fluid samples derived from 6034 pregnant women. RESULTS: Both QF-PCR and
      karyotyping analysis have detected 135 cases of fetal aneuploidies involving
      chromosomes 21, 18, 13, X, and Y. The QF-PCR assay was also successful in 67
      cases for which amniotic fluid culture has failed. Furthermore, it has identified
      maternal cell contamination in 7 cases. By determining the consistency of short
      tandem repeat (STR) sites, the QF-PCR assay has identified 22 dizygotic twins
      among 32 twins with double chorions and double amniotic sacs. In 12 cases, it has
      signaled numerical chromosomal aberration by critical or partial abnormal values
      for the fluorescence peak area ratio, which were verified by karyotyping analysis
      as mosaicisms of chromosome aneuploidies. CONCLUSION: The QF-PCR can provide an
      useful supplement for chromosomal karyotyping and has an important role in rapid
      prenatal diagnosis.

PMID- 29652999
TI  - [Application of single nucleotide polymorphism microarray and fluorescence in
      situ hybridization analysis for the prenatal diagnosis of a case with Pallister
      Killian syndrome].
AB  - OBJECTIVE: To explore the clinical and genetic characteristics of a case with
      Pallister-Killian syndrome (PKS). METHODS: Chromosomal karyotype of umbilical
      cord blood sample derived from a 36-year-old pregnant woman was analyzed by G
      banding analysis. After birth, the child was further analyzed with single
      nucleotide polymorphism microarray (SNP array) and fluorescence in situ
      hybridization (FISH) using 12pter/12qter probes. RESULTS: G-banding analysis
      showed that the fetus has a karyotype of 46,XY [77]/47,XY,+mar [23]. After birth,
      Affymetrix CytoScan 750K array analysis showed a segmental tetrasomy of arr
      [hg19] 12p13.33p11.1(173 786 - 34 835 641)*4 and a 34.6 Mb repeat at
      12p13.33p11.1 with in the neonate. FISH analysis confirmed that 39% of cells
      harbored the 12p tetrasomy. CONCLUSION: Combined clinical examination, G-banded
      chromosomal karyotyping, FISH and microarray analysis can delineate the origin
      and fragments of small supernumerary marker chromosomes and diagnose PKS with
      precision.

PMID- 29653000
TI  - [Application of combined chromosomal karyotyping and BACs-on-Beads assay for the
      prenatal diagnosis of high-risk gravida from Ningbo].
AB  - OBJECTIVE: To assess the value of combined chromosomal karyotyping and BACs-on
      Beads(BoBs) assay for the prenatal diagnosis of high risk gravida from Ningbo.
      METHODS: For 2779 women, results of conventional karyotyping analysis and BoBs
      assay were compared. RESULTS: For common aneuploidies involving chromosomes 13,
      18, 21, X and Y, the two methods have yielded a concordance rate of 98.78%. Eight
      cases detected with microduplication by BoBs were missed by karyotyping analysis.
      On the other hand, 17 structural chromosomal abnormalities, 10 chimeras and 1
      triploidy detected by karyotyping analysis were missed by BoBs. CONCLUSION: The
      BoBs technology has featured high throughput and rapidity, and can detect 9
      microdeletion syndromes, which can improve the quality of prenatal diagnosis and
      provide an ideal complementary for conventional chromosomal karyotyping.

PMID- 29653001
TI  - [Genetic analysis of two fetuses with congenital heart defects and 3q
      microdeletion].
AB  - OBJECTIVE: To determine the nature of genomic copy number variations (CNVs) in
      two fetuses with congenital heart defects (CHD) and explore the correlation
      between 3q microdeletions and CHD. METHODS: Genomic DNA was extracted from fetal
      umbilical cord tissue, and chromosome copy number variations were detected by low
      coverage whole genome sequencing. RESULTS: Both fetuses had microdeletions of the
      long arm of chromosome 3. Fetus 1 had ventricular septal defect, cleft lip and
      palate, and a 1.66 Mb deletion on 3q29. The deleted region encompassed all of the
      critical genes for 3q29 microdeletion syndrome. Fetus 2 had overriding aorta,
      ventricular septal defect, and a novel 240 kb deletion on 3q28. CONCLUSION: 3q29
      microdeletion may result in CHD in combination with cleft lip and palate. Genomic
      CNVs can be detected by low coverage whole genome sequencing.

PMID- 29653002
TI  - [Genetic analysis of two children patients affected with CHARGE syndrome].
AB  - OBJECTIVE: To analyze two Chinese pediatric patients with multiple malformations
      and growth and development delay. METHODS: Both patients were subjected to
      targeted gene sequencing, and the results were analyzed with Ingenuity Variant
      Analysis software. Suspected pathogenic variations were verified by Sanger
      sequencing. RESULTS: High-throughput sequencing showed that both patients have
      carried heterozygous variants of the CHD7 gene. Patient 1 carried a nonsense
      mutation in exon 36 (c.7957C>T, p.Arg2653*), while patient 2 carried a nonsense
      mutation of exon 2 (c.718C>T, p.Gln240*). Sanger sequencing confirmed the above
      mutations in both patients, while their parents were of wild-type for the
      corresponding sites, indicating that the two mutations have happened de novo.
      CONCLUSION: Two patients were diagnosed with CHARGE syndrome by high-throughput
      sequencing.

PMID- 29653003
TI  - [Diagnosis of two neonates with galactosemia by using next generation
      sequencing].
AB  - OBJECTIVE: To explore the genetic basis of two neonates suspected for
      galactosemia. METHODS: Next generation sequencing(NGS) was used to screen the
      whole exome of the neonates. Suspected mutation was validated by PCR and Sanger
      sequencing. Potential impact of novel mutation was predicted by using PolyPhen-2,
      MutationTaste and SIFT software. RESULTS: Both neonates harbored compound
      heterozygous mutations of the GALT gene inherited from their parents. One has
      inherited two novel mutations c.564G>C(p.Q188H) and c.116A>T(p.D39V) respectively
      from his father and mother. The other has inherited mutations c.754C>T(p.Q252X)
      and c.904+1G>T from her father and mother, respectively. CONCLUSION: The
      galactosemia in the two neonates may be attributed to compound heterozygous
      mutations of the GALT gene. This is the first domestic report of using the NGS
      for the diagnosis of galactosemia.

PMID- 29653004
TI  - [Genetic analysis of a child with cleidocranial dysplasia and 6q21-q22.31
      microdeletion].
AB  - OBJECTIVE: To carry out genetic analysis on a child with developmental delay and
      multiple malformation. METHODS: The karotypes of the child and her parents were
      analyzed with routine chromosomal G-banding. Their genomic DNA was analyzed with
      array comparative genomic hybridization (aCGH). RESULTS: The karyotype of the
      proband was determined as 46,XX,del(6)(q22),inv(6)(p21.1q21), while no karyotypic
      abnormality was detected in her parents. aCGH has identified in the child a de
      novo 800 kb deletion encompassing the RUNX2 gene at 6p21.1 and a de novo 11.79 Mb
      deletion at 6q21-q22.31. CONCLUSION: Both of the de novo deletions are
      pathogenic. Deletion of the RUNX2 gene probably underlies the cleidocranial
      dysplasia in the patient, while the 6q21-q22.31 deletion may result in
      malformation of the brain.

PMID- 29653005
TI  - [Analysis of a patient with X-linked mental retardation by next generation
      sequencing].
AB  - OBJECTIVE: To explore the clinical and genetic features of a Chinese boy
      featuring X-linked mental retardation. METHODS: Clinical features of the patient
      were analyzed. The DNA of the patient and his parents was extracted and sequenced
      by next generation sequencing. The results were validated and analyzed with
      software. RESULTS: The child displayed X-linked mental retardation. Sequencing
      showed the patient has carried a c.455T>C (p.L152P) mutation of the GRIA3 gene
      inherited from his mother. CONCLUSION: The c.455T>C (p.L152P) mutation of the
      GRIA3 gene probably underlies the X-linked mental retardation in this child.

PMID- 29653006
TI  - [A weak D type 59 case identified in the Chinese Han population].
AB  - OBJECTIVE: To study a case with weak D59 phenotype identified among ethnic Han
      Chinese population. METHODS: Routine serological tests were used to analyze the
      reaction patterns, and the RhD epitopes were verified with 12 monoclonal
      antibodies. Sequence-specific primer PCR was applied for typing the weak RhD and
      RhD zygosity in the proband and his family members. RESULTS: A c.1148T>C variant
      was identified in the proband, for which serological test indicated a weak D
      phenotype. RHD zygosity testing confirmed that the proband had a RHD+ /RHD-
      genotype. CONCLUSION: A weak D59 phenotype was firstly identified in a Chinese
      individual.

PMID- 29653007
TI  - [Analysis of TGM1 gene mutation in a collodion baby].
AB  - OBJECTIVE: To explore the genetic cause for a Uyghur Chinese child with collodion
      skin. METHODS: G-banded chromosomal karyotyping was carried out for the child and
      his parents. High-throughput sequencing for 25 genes related to ichthyosis and
      ichthyosiform dermatosis was also performed for the child. RESULTS: No karyotypic
      abnormality was found in the child and his parents. High-throughput sequencing
      has detected in the patient a previously described pathogenic mutation c.919C>T
      (p.Arg307Trp) and a novel c.856C>T (p.Arg286Trp) mutation in the TGM1 gene. By
      Sanger sequencing, the child was verified to have carried both mutations. His
      father was found to be a heterozygous carrier of the c.856C>T (p.Arg286Trp)
      mutation, while neither mutation was found in the mother. CONCLUSION: Congenital
      ichthyosis associated with the TGM1 gene may show an autosomal recessive
      inheritance. The collodion condition of the child is probably due to the compound
      heterozygous mutations of the TGM1 gene.

PMID- 29653008
TI  - [A de novo GJA1 mutation identified by whole-exome sequencing in a patient with
      oculodentodigital dysplasia].
AB  - OBJECTIVE: To explore the genetic basis for a patient with oculodentodigital
      dysplasia. METHODS: Genomic DNA was extracted from peripheral blood samples from
      the patient and his parents. Whole-exome sequencing was carried out for the trio
      family. Suspected mutation was verified by Sanger sequencing. RESULTS: A de novo
      c.412G>A mutation of the GJA1 gene was identified in the patient, which was
      validated by Sanger sequencing. CONCLUSION: The c.412G>A mutation of the GJA1
      gene probably underlies the disease in the patient.

PMID- 29653009
TI  - [Cytogenetic and molecular genetic analysis of the amniotic fluid cells of a
      fetus with pseudodicentric isochromosome 22 resulting in partial tetraploidy of
      22q].
AB  - OBJECTIVE: To diagnose chromosomal abnormalities in amniotic fluid cells by
      combining karyotyping and single nucleotide polymorphism array (SNP-array)
      analysis, and to explore the application of SNP-array in routine clinical
      practice. METHODS: Conventional G banding was used to karyotype a fetal amniotic
      fluid sample and the corresponding peripheral blood samples from the parents,
      followed by SNP-array analysis of the fetal genomic DNA from the amniotic fluid.
      RESULTS: The karyotype of the amniocytes was 47, XX, +mar. The marker chromosome
      was further identified as psu idic (22) (q11.2) by SNP-array analysis, revealing
      tetraploidy of a 1.7 Mb fragment in 22q11.1-q11.2 interval that involves the
      critical region for Cat eye syndrome. CONCLUSION: A rare chromosomal abnormality
      was identified by combining conventional G banding and SNP-array. The high
      resolution SNP-array could provide more detailed information for determining the
      origin of chromosomal abnormalities.

PMID- 29653010
TI  - [Transformation from promyelocytic leukemia with t (15; 17) ( q22; q21) to acute
      monocytic leukemia with t (11; 17) (q23; q21) in a case].
AB  - OBJECTIVE: To report on a case of therapy-related acute monocytic leukemia(t-AML)
      with t(11;17) (q23;q21)/MLL-AF17q after successful treatment for acute
      promyelocytic leukemia(APL) with t(15;17) (q22;q21)/PML-RARalpha. METHODS: A MICM
      method (bone marrow morphology(M), immunophenotype(I), cytogenetics(C), and
      molecular biology(M)) was used for the diagnosis and classification of the
      disease at the time of onset and transformation. RESULTS: The patient was
      initially identified with typical morphology and immunophenotype of APL. She has
      carried t(15;17)(q22;q21) and PML-RARalpha fusion gene but was without
      t(11;17)(q23;q21) or MLL gene abnormalities. After 13 months of successful
      treatment, she has transformed to AML with typical morphology and
      immunophenotype. t(11;17)(q23;q21) and MLL-AF17q fusion gene were detected in her
      bone marrow sample, while no PLZF-RARalpha fusion gene was detected by real-time
      quantitative reverse-transcription PCR(RQ-PCR) and fluorescence in situ
      hybridization(FISH). CONCLUSION: t-AML is a serious complication after successful
      treatment of APL. t(11;17)(q23;q21) is not specific for the diagnosis of variant
      APL and can also be detected in t-AML. RQ-PCR and FISH are essential for the
      diagnosis of such patients.

PMID- 29653011
TI  - [Advance in clinical research on Antley-Bixler syndrome].
AB  - Antley-Bixler syndrome (ABS) is a rare childhood disorder affecting skeletal
      development. Some patients may also have genital anomalies and impaired
      steroidogenesis. Diagnostic criteria for ABS has not been fully established,
      though craniosynostosis, midface hypoplasia and elbow synostosis are minimum
      requirements. The etiology of ABS is complex, which included autosomal dominant
      form caused by FGFR2 gene mutations, autosomal recessive form caused by POR gene
      mutations, and high oral dose of fluconazole during pregnancy. Patients may die
      from dyspnea due to upper respiratory tract obstruction. This review summarizes
      research progress on the clinical features, etiology, differential diagnosis,
      treatment and prevention of ABS.

PMID- 29653012
TI  - [Advance in research on spinocerebellar ataxia 2].
AB  - Spinocerebellar ataxia type 2 (SCA2) is a rare autosomal dominant progressive
      degenerative disease of the nervous system, which is characterized by a
      progressive cerebellar syndrome associated with saccadic eye scan, peripheral
      neuropathy, cognitive disorders, and other multisystem features. The gene
      predisposing to SCA2 has been mapped, which encodes the ataxin 2 protein. A CAG
      repeat expansion in the coding region of ATXN2 gene can cause extension of
      polyglutamine chain in the protein. This paper reviews recent progress made in
      the research on SCA2 in regard to its clinical features, pathology, etiology,
      pathogenesis and treatment.

PMID- 29653013
TI  - [Progress of research on Bardet-Biedl syndrome].
AB  - Bardet-Biedl syndrome (BBS) is a rare genetic disease caused by ciliary structure
      abnormality or dysfunction. To date, more than 21 BBS genes (BBS1 - 21) have been
      reported to independently cause the disorder. Although the cellular functions of
      BBS proteins are not yet fully understood, model organisms have revealed that
      such proteins are involved in ciliary functions and intracellular transport.
      Among the 21 BBS genes, BBS7 is unique in that its product is a subunit of the
      BBSome and can directly interact with the BBS chaperonin complex. Previous
      studies using animal models showed that BBS7 mutation can cause similar
      phenotypes to human patients, and human disease caused by BBS7 variants are
      special and more complex. This article reviewed recent progresses on BBS7.

PMID- 29653014
TI  - [Diffuse palmoplanta keratoderma: a pedigree with 23 cases].

PMID- 29653015
TI  - A novel HLA-C allele, HLA-C*07:02:01:17N, with an alternative splice site.
AB  - We describe the identification of alternatively expressed HLA allele
      C*07:02:01:17N.

PMID- 29653017
TI  - CRPS Knee: How Frequently Encountered in Differential Diagnosis of Knee Pain?

PMID- 29653016
TI  - Accelerated Forced Degradation of Pharmaceuticals in Levitated Microdroplet
      Reactors.
AB  - Forced degradation is a method of studying the stability of pharmaceuticals in
      order to design stable formulations and predict drug product shelf life.
      Traditional methods of reaction and analysis usually take multiple days, and
      include LC-UV and LC-MS product analysis. In this study, the reaction/analysis
      sequence was accelerated to be completed within minutes using Leidenfrost
      droplets as reactors (acceleration factor: 23-188) and nanoelectrospray
      ionization MS analysis. The Leidenfrost droplets underwent the same reactions as
      seen in traditional bulk solution experiments for three chemical degradations
      studied. This combined method of accelerated reaction and analysis has the
      potential to be extended to forced degradation of other pharmaceuticals and to
      drug formulations. Control of reaction rate and yield is achieved by manipulating
      droplet size, levitation time and whether or not make-up solvent is added.
      Evidence is provided that interfacial effects contribute to rate acceleration.

PMID- 29653018
TI  - Brain complications of diabetes mellitus: a cross-sectional study of awareness
      among individuals with diabetes and the general population in Ireland.
AB  - AIMS: To identify awareness of potential brain complications of diabetes among
      individuals with diabetes and the public. METHODS: For this observational, cross
      sectional survey study, we recruited consecutive adult attendees of a specialist
      diabetes clinic and two primary care practices. Primary care attendees
      represented members of the general population of Ireland. An interviewer
      administered questionnaire was used to gather data on respondents' awareness of
      brain complications of diabetes and modifiable risk factors for dementia.
      Multivariable logistic regression was undertaken to identify variables
      independently associated with awareness. RESULTS: Respondents included a total of
      502 adults: 250 in the diabetes group (37% women, mean age 63 +/- 14 years, 88%
      with Type 2 diabetes) and 252 in the general population group (51% women, mean
      age 47 +/- 17 years, 7% with Type 2 diabetes). The diabetes group had
      significantly greater awareness of diabetes complications, except for depression,
      compared with the general population group. In the group as a whole, respondent
      awareness of dementia (35%) and memory problems (47%) as potential complications
      of diabetes was poor compared with awareness of kidney (84%) and eye damage
      (84%). Respondents were 1.5 times more likely to identify that individuals can
      modify their risk of developing Type 2 diabetes than their risk of dementia.
      CONCLUSIONS: This study shows that there is poor awareness of brain complications
      of diabetes among individuals with diabetes and the general population in
      Ireland. The results suggest a need for expansion of public awareness campaigns
      and diabetes education programmes to promote awareness of the brain complications
      of diabetes and of the modifiable risk factors for dementia, as part of a life
      course approach to dementia prevention.

PMID- 29653019
TI  - Bilateral ipilimumab-induced posterior uveitis following treatment for metastatic
      choroidal melanoma.

PMID- 29653021
TI  - Characterization of the novel HLA-B*40:366 allele by sequencing-based typing.
AB  - HLA-B*40:366 differs from HLA-B*40:06:01:01 by one nucleotide substitution at
      position 362.

PMID- 29653020
TI  - Developmental toxicity of flucytosine following administration to pregnant rats
      at a specific time point of organogenesis.
AB  - To investigate the abnormalities that are specific to administration of
      flucytosine at one time point during embryonic organogenesis, flucytosine was
      administered orally to pregnant Sprague Dawley (SD) rats in a single dose on day
      11 of pregnancy at 25 or 35 mg/kg. Fetuses on day 20 of pregnancy were
      externally, viscerally, and skeletally examined. Maternal body weight gain and
      food consumption were suppressed the day after administration of a 35 mg/kg.
      Fetal examinations revealed various alterations in both dose groups: externally
      preaxial polydactyly in the hind limb; skeletally fused lumbar centrum, absent
      sacral centrum, supernumerary sacral vertebra, and absent ribs. Our findings
      indicated that specific types of external and skeletal anomalies were induced
      following flucytosine administration on day 11 of pregnancy.

PMID- 29653022
TI  - Characterization of the novel HLA-DQB1*06:02:29 allele by sequencing-based
      typing.
AB  - HLA-DQB1*06:02:29 differs from HLA-DQB1*06:02:01:01 by one nucleotide
      substitution at position 408 (C > T).

PMID- 29653023
TI  - gamma-Aminobutyric acid quantification in small volume biological samples through
      enzymatically induced electrochemiluminescence.
AB  - gamma-Aminobutyric acid (GABA) is a well-known neurotransmitter that regulates
      inhibitory neurotransmission in the mammalian central nervous system and
      participates in several processes outside the brain. A reliable quantification
      method is needed to determine its role in different physiological and
      pathological conditions. However, GABA measurements have several challenges
      because GABA is neither fluorescent nor electroactive, and it is difficult to
      detect using enzymatic reactions because no oxidases or dehydrogenases have been
      identified. Several methods have been developed to quantify GABA concentrations
      based on the instrumentation available, the sensitivity required, and the volume
      of samples analyzed. Most of these methods use high-performance liquid
      chromatography (HPLC). Here, we describe a method for quantifying GABA
      concentrations in small volume samples using enzymatically-induced
      electrochemiluminescence with the well-known GABAse complex, which produces
      glutamate for use in a luminescent reaction with glutamate oxidase and luminol in
      an electrochemiluminescence cell. The luminescence obtained was proportional to
      the GABA concentrations in the micromolar range (1-1000), with linear r2 values >
      0.95. GABA standards were treated with the enzymatic reactors to generate
      glutamate (Glu), which was measured simultaneously with an HPLC technique, to
      validate this new procedure. The assay was further used to determine GABA
      concentrations in hippocampal extracts. This alternative may be used to quantify
      GABA levels in fluid samples, such as microdialysates, other perfusates and
      tissue extracts. Thus, the method presented here is a good alternative for
      monitoring GABA levels with good sensitivity compared with the traditional
      methods that are still in use.

PMID- 29653024
TI  - Reaction Kinetics Direct a Rational Synthesis of an HIV-1 Inactivator of
      Nucleocapsid Protein 7 and Provide Mechanistic Insight into Cellular Metabolism
      and Antiviral Activity.
AB  - Mercaptobenzamide thioester SAMT-247 is a non-toxic, mutation-resistant HIV-1
      maturation inhibitor with a unique mechanism of antiviral activity. NMR
      spectroscopic analyses of model reactions that mimic the cellular environment
      answered fundamental questions about the antiviral mechanism and inspired a high
      yielding (64 % overall), scalable (75 mmol), and cost-effective ($4 mmol-1 )
      three-step synthesis that will enable additional preclinical evaluation.

PMID- 29653025
TI  - Characterization of the novel HLA-C*07:613 allele by sequencing-based typing.
AB  - HLA-C*07:613 differs from HLA-C*07:01:01:01 by one nucleotide substitution at
      position 454.

PMID- 29653026
TI  - The full-length genomic sequence of a novel HLA-C*07 allele, HLA-C*07:63,
      identified in a Chinese individual.
AB  - HLA-C*07:63 differs from HLA-C*07:04:01 by a single nonsynonymous change,
      resulting in an amino acid substitution.

PMID- 29653027
TI  - The relationship among breakfast time, morningness-eveningness preference and
      body mass index in Type 2 diabetes.
AB  - AIMS: Obesity is prevalent and related to poor outcomes in Type 2 diabetes.
      Evening preference and late meal times have been shown to be associated with
      obesity, but data are lacking in people with Type 2 diabetes. This study examined
      the relationship among meal timing, morningness-eveningness preference and BMI in
      Type 2 diabetes, using a mediation analysis. METHODS: Some 210 non-shift workers
      with Type 2 diabetes participated in the study. Morningness-eveningness
      preference was assessed using a standard questionnaire, the Composite Scale of
      Morningness (CSM). Meal timing and daily calorie intake were obtained from 1-day
      food recall. A mediation analysis adjusting for relevant covariables was
      performed to explore whether morningness-eveningness had a direct effect on BMI,
      or whether the effect was mediated through the intermediate variable of meal
      timing. RESULTS: Mean BMI was 28.4 +/- 4.8 kg/m2 . A higher BMI was associated
      with greater evening preference (P = 0.019), and non-significantly associated
      with late breakfast time (P = 0.053). BMI was not associated with other mealtimes
      or calorie intake. In addition, evening preference was associated with late
      breakfast time (P < 0.001). Mediation analysis revealed that breakfast time
      mediated the association between morningness-eveningness and BMI, i.e. morning
      preference (CSM >= 45) was associated with earlier breakfast time, and lower BMI
      by 0.37 kg/m2 [coefficient = -0.365, 95% confidence intervals (CI): -0.877, 
      0.066), whereas the direct relationship between BMI and morningness-eveningness
      was non-significant. CONCLUSIONS: Late breakfast time mediated the relationship
      between morningness-eveningness preference and BMI. These results suggest that
      circadian preference and meal timing are novel and possibly modifiable risk
      factors for obesity in Type 2 diabetes.

PMID- 29653028
TI  - RNA localization regulates diverse and dynamic cellular processes.
AB  - At the nexus of specialized cellular responses are localized enrichments of
      protein activity. The localization of messenger RNA (mRNA) coupled with
      translational control often plays a crucial role in the generation of protein
      concentrations at defined subcellular domains. Although mRNA localization is
      classically associated with large specialized cells, such as neurons and embryos,
      RNA localization is a highly conserved paradigm of post-transcriptional
      regulation observed in diverse cellular contexts. Functions of localized mRNAs
      extend far beyond the well-studied examples of neuronal polarization and
      developmental patterning. Since the initial discovery of the intracellular
      localization of cytoskeletal mRNAs within migrating cells, hundreds of mRNAs are
      now known to be enriched at specific organelles where they contribute to cell
      function. In this short review, we discuss basic principles regulating RNA
      localization and consider the contribution of localized mRNA to several essential
      cellular behaviors. We consider RNA localization as a mechanism with widespread
      implications for cellular function.

PMID- 29653029
TI  - Prostate-specific membrane antigen-targeted photoacoustic imaging of prostate
      cancer in vivo.
AB  - A sensitive, noninvasive method to detect localized prostate cancer, particularly
      for early detection and repetitive study in patients undergoing active
      surveillance, remains an unmet need. Here, we propose a molecular photoacoustic
      (PA) imaging approach by targeting the prostate-specific membrane antigen (PSMA),
      which is over-expressed in the vast majority of prostate cancers. We performed
      spectroscopic PA imaging in an experimental model of prostate cancer, namely, in
      immunocompromised mice bearing PSMA+ (PC3 PIP) and PSMA- (PC3 flu) tumors through
      administration of the known PSMA-targeted fluorescence agent, YC-27. Differences
      in contrast between PSMA+ and isogenic control tumors were observed upon PA
      imaging, with PSMA+ tumors showing higher contrast in average of 66.07-fold with
      5 mice at the 24-hour postinjection time points. These results were corroborated
      using standard near-infrared fluorescence imaging with YC-27, and the squared
      correlation between PA and fluorescence intensities was 0.89. Spectroscopic PA
      imaging is a new molecular imaging modality with sufficient sensitivity for
      targeting PSMA in vivo, demonstrating the potential applications for other
      saturable targets relevant to cancer and other disorders.

PMID- 29653031
TI  - Desperately seeking subjects: Increasingly specific criteria have left cancer
      trial researchers competing for a few viable candidates.

PMID- 29653030
TI  - Sex modulates the association of fibroblast growth factor 21 with end-stage renal
      disease in Asian people with Type 2 diabetes: a 6.3-year prospective cohort
      study.
AB  - AIM: To study whether plasma fibroblast growth factor 21 independently predicts
      the risk of end-stage renal disease in Asian people with Type 2 diabetes.
      METHODS: In this prospective cohort study, 1700 Asian people with Type 2 diabetes
      were followed for a mean of 6.3 years in a regional hospital in Singapore.
      Incident end-stage renal disease was identified by linkage with a national renal
      registry. The association of baseline fibroblast growth factor 21 levels with
      risk of progression to end-stage renal disease was studied using survival
      analyses. RESULTS: Participants were aged 60 +/- 10 years, with an average
      diabetes duration of 12 years. Their estimated GFR was 73 +/- 28 ml/min/1.73 m2
      and 62% had albuminuria at baseline. A total of 179 incident end-stage renal
      disease cases were identified. Plasma fibroblast growth factor 21 interacted with
      sex in its association with end-stage renal disease (Pinteraction = 0.003). A 1
      sd increment in fibroblast growth factor 21 (natural log-transformed) was
      associated with a 1.32-fold (95% CI 1.05-1.66, P = 0.02) increased hazard for end
      stage renal disease in women, after adjustment for traditional risk factors
      including estimated GFR and albuminuria. Taking death as a competing risk did not
      materially change the outcome [sub-distribution hazard ratio 1.35 (95% CI 1.11
      1.66, P = 0.003)]. Fibroblast growth factor 21 did not predict end-stage renal
      disease risk in men after adjustment for baseline estimated GFR and albuminuria
      [hazard ratio 1.07 (95% CI 0.89-1.28, P = 0.49)]. CONCLUSIONS: Plasma fibroblast
      growth factor 21 level independently predicted risk of progression to end-stage
      renal disease in women with Type 2 diabetes. The pathophysiological relationships
      among FGF21, sex and renal progression warrant further study.

PMID- 29653032
TI  - Characterization of the novel HLA-DQB1*03:279 allele by sequencing-based typing.
AB  - HLA-DQB1*03:279 differs from HLA-DQB1*03:02:01:01 by one nucleotide substitution
      at position 218 (A>T).

PMID- 29653034
TI  - KIR2DL1 allele sequence extensions and discovery of 2DL1*0010102 and 2DL1*0010103
      alleles by DNA sequencing.
AB  - Full-length KIR2DL1 allele sequence extensions characterised by single molecule
      real-time (SMRT) DNA sequencing.

PMID- 29653033
TI  - Organometallic Conjugates of the Drug Sulfadoxine for Combatting Antimicrobial
      Resistance.
AB  - Fourteen novel arene RuII , and cyclopentadienyl (Cpx ) RhIII and IrIII complexes
      containing an N,N'-chelated pyridylimino- or quinolylimino ligand functionalized
      with the antimalarial drug sulfadoxine have been synthesized and characterized,
      including three by X-ray crystallography. The rhodium and iridium complexes
      exhibited potent antiplasmodial activity with IC50 values of 0.10-2.0 MUm in
      either all, or one of the three Plasmodium falciparum assays (3D7 chloroquine
      sensitive, Dd2 chloroquine resistant and NF54 sexual late stage gametocytes) but
      were only moderately active towards Trichomonas vaginalis. They were active in
      both the asexual blood stage and the sexual late stage gametocyte assays, whereas
      the clinical parent drug, sulfadoxine, was inactive. Five complexes were
      moderately active against Mycobacterium tuberculosis (IC50 <6.3 MUm), while
      sulfadoxine showed no antitubercular activity. An increase in the size of both
      the Cpx ligand and the aromatic imino substituent increased hydrophobicity, which
      resulted in an increase in antiplasmodial activity.

PMID- 29653035
TI  - Sugarcane growth and nutrition levels are differentially affected by the
      application of PGPR and cane waste.
AB  - Mineral and organic fertilization can be optimized by using rhizobacteria which
      increases dry matter, yield, and nutrients in the soil and plant, among the other
      biological inputs. However, the discovery of single microbes or a consortium that
      can benefit plants has been a challenge. In this context, this study aimed to
      evaluate the effects of Bacillus subtilis and Bacillus pumilus combined with
      mineral fertilization and sugar and alcohol industry by-products in presprouted
      and the initial growth phase of sugar cane seedlings. The study was carried out
      in two phases. Phase 1 included presprouted seedlings with T1 =  untreated
      control, T2 =  B. subtilis, T3 =  B. pumilus, and T4 =  B. subtilis + B. pumilus
      treatments. Phase 2 included the same treatments with four types of
      fertilization: F1 =  mineral fertilization, F2 =  mineral fertilization +
      vinasse, F3 =  mineral fertilization + filter cake, and F4 =  mineral
      fertilization + filter cake compost. Of the phase 1 treatments, T2 (B. subtilis)
      was the best promoter of root growth and the total dry matter compared to the
      control with an increase of 23.0% compared to the control. In phase 2, B. pumilus
      application, increased the total dry matter by 13%, the number of tillers by 37%,
      and the diameter of the tillers by 48% when combined with mineral fertilization.
      The combined application of B. subtilis and B. pumilus increased the phosphorus
      content by 13% in soil treated with mineral fertilization and filter cake
      compost. The results of the this study strongly suggest that the use of B.
      subtilis and B. pumilus together with these by-products can improve soil
      fertility parameters and decrease adverse effects associated with vinasse
      fertilization, in addition to providing shoot and root growth and providing
      collective synergy for a high yield of sugarcane production with environmental
      benefits.

PMID- 29653036
TI  - Factors that predict walking ability with a prosthesis in lower limb amputees.
AB  - Introduction: Identification of predictive factors for walking ability with a
      prosthesis, after lower limbamputation, is very important in order to define
      patient's potentials and realistic rehabilitation goals,however challenging they
      are. Objective: The objective of this study was to investigate whether variables
      determined at the beginningof rehabilitation process are able to predict walking
      ability at the end of the treatment using supportvector machines (SVMs). Methods:
      This research was designed as a retrospective clinical case series. The outcome
      was defined asthree-leveled ambulation ability. SVMs were used for predicting
      model forming. Results: The study included 263 patients, average age 60.82 +/-
      9.27 years. In creating SVM models, elevenvariables were included: age, gender,
      cause of amputation, amputation level, period from amputation toprosthetic
      rehabilitation, Functional Comorbidity Index (FCI), presence of diabetes,
      presence of a partner,restriction concerning hip or knee extension, residual limb
      hip extensor strength, and mobility at admission.Six SVM models were created with
      four, five, six, eight, 10, and 11 variables, respectively. Geneticalgorithm was
      used as an optimization procedure in order to select the best variables for
      predicting thelevel of walking ability. The accuracy of these models ranged from
      72.5% to 82.5%. Conclusion: By using SVM model with four variables (age, FCI,
      level of amputation, and mobility at admission)we are able to predict the level
      of ambulation with a prosthesis in lower limb amputees withhigh accuracy.

PMID- 29653037
TI  - Manual versus target-controlled infusion of balanced propofol during diagnostic
      colonoscopy - A prospective randomized controlled trial.
AB  - Introduction: There is an increasing interest in balanced propofol sedation (BPS)
      for colonoscopy inoutpatient settings. Propofol is a potent anesthetic agent for
      this purpose and has a narrow therapeuticrange, which increases a risk of
      cardiovascular and respiratory complications in case of improperadministration.
      Objective: The aim of this study was to compare patients' safety and comfort of
      endoscopists in twomethods of BPS targeting deep sedation - propofol target
      controlled infusion (TCI) and manual intravenoustitration technique (MT) - during
      colonoscopy. Methods: This prospective randomized controlled trial included 90
      patients (class I or II of the AmericanSociety of Anesthesiologists) deeply
      sedated with propofol, coadministered with small doses of midazolamand fentanyl.
      Propofol was given by MT technique (45 patients) or by TCI (45 patients). The
      followingadverse effects were recorded: hypotension, hypertension, bradycardia,
      tachycardia, hypoxemia,bradypnea, apnea, hiccupping, and coughing, as well as
      endoscopist's comfort during colonoscopy bymeans of a questionnaire. Results: The
      MT group compared to the TCI group had a lower mean arterial pressure in the 10th
      minuteafter the beginning (p = 0.017), and at the end of colonoscopy (p = 0.006),
      higher oxygen saturation inthe fifth minute (p = 0.033), and in the 15th minute
      (p = 0.008) after the beginning of colonoscopy, andlower heart rate at the
      beginning of the procedure (p = 0.001). There were no statistically significant
      differencesin adverse events. Endoscopist's comfort during colonoscopy was high
      95.6% in the TCI groupvs. 88.9% in the MT group (p = 0.069). Conclusion: MT is
      clinically as stable as TCI of propofol for deep sedation during colonoscopy, and
      endoscopistsexperienced the same comfort during colonoscopy in both groups. Thus,
      both combinationsare suitable for deep sedation during diagnostic colonoscopy.

PMID- 29653038
TI  - Streptococcus pneumoniae serotype distribution in Vojvodina before the
      introduction of pneumococcal conjugate vaccines into the National
      ImmunizationProgram.
AB  - Introduction: Streptococcus pneumoniae is the most common causative agent of
      bacterial pneumoniaand meningitis. Mandatory childhood immunization against
      pneumococcal diseases is introduced in thenew Law on Protection of Population
      against Communicable Diseases in Serbia. Objective: The objective of this study
      was to determine the prevalence of pneumococcal serotype distributionin Vojvodina
      region before routine use of pneumococcal conjugate vaccine in Serbia. Methods: A
      total of 105 isolates of Streptococcus pneumoniae were collected in the period
      from January2009 to April 2016. Based on the results of serotyping in the
      National Reference Laboratory, we analyzeddistribution of circulating serotypes
      and coverage of conjugate and 23-valent polysaccharide pneumococcalvaccines in
      different age groups. Results: Among 105 isolates, a total of 21 different
      serotypes of Streptococcus pneumoniae were determined.The most frequent serotypes
      were 3 (21.9%), 19F (20.0%), and 14 (10.5%). The serotype coverage ofpneumococcal
      conjugate vaccines (PCV7, PCV10, and PCV13) was 48.6%, 54.3%, and 84.8%,
      respectively,while pneumococcal polysaccharide vaccine (PPV23) covered 89.5% of
      the total number of isolates in allage groups. Serotypes included in PCV7, PCV10,
      and PCV13 represented 72.0%, 76.0%, and 88.0% of thetotal number of isolates in
      children <=5 years, respectively. Vaccine serotype coverage of PCV13 and
      PPV23ranged from 87.1% to 90.3% in adults 50-64 years of age, and 77.8% to 85.2%
      in adults >=65 years old. Conclusion: Serotype distribution of Streptococcus
      pneumoniae in the population fairly overlaps with theserotypes contained in
      pneumococcal vaccines, so that implementation of childhood immunization
      isjustified. The study was done in the Province of Vojvodina but the findings may
      be applied to Serbia asa whole.

PMID- 29653039
TI  - Relentless placoid chorioretinitis - A case report.
AB  - Introduction: Relentless placoid chorioretinitis is an entity which belongs to
      the group of an atypicalintermediate form of primary inflammatory
      choriocapillaropathies, resembling both acute posteriormultifocal placoid pigment
      epitheliopathy and serpiginous choroiditis, but the retinal distribution
      andclinical course are not the same. Because of this similarity this entity was
      termed "AMPPiginous". Thisentity was first described by Jones et al. in 2000. The
      aim of our case report is to present a very specificcase where the clinical
      course was progressive, with loss of vision in the affected eye. Case Outline: A
      31-year-old man, with no previous ophthalmic diseases, was hospitalized at the
      Clinicof Ophthalmology, Clinical Center Kragujevac, because of a reduction of
      vision in the right eye, andscotoma and metamorphopsia in the left eye. The
      clinical course of retinal lesions in the left eye resembledthe changes observed
      in acute posterior multifocal placoid pigment epitheliopathy, and the righteye
      changes were between acute posterior multifocal placoid pigment epitheliopathy
      and serpiginouschoroiditis. The diagnosis of relentless placoid chorioretinitis
      was confirmed after clinical, laboratory,immunological, virological, and
      angiography examinations. Conclusion: The progressive clinical course of the
      disease, complemented by multimodal imaging andextensive laboratory diagnostics,
      has led us to the diagnosis of relentless placoid chorioretinitis. Thecombined
      anti-inflammatory and immunomodulatory therapy led to the stabilization of visual
      acuityof the left eye as opposed to the right, where there has been no recovery.

PMID- 29653040
TI  - Central mucoepidermoid carcinoma of the mandible - A case report.
AB  - Introduction: Mucoepidermoid carcinoma, compared to other tumors of salivary
      glands, occurs in 5-10%of cases. Histopathologically, it is divided into a well
      differentiated tumor that is of low-grade of malignancy,and a medium and poorly
      differentiated tumor of high grade of malignancy. Central mucoepidermoidcarcinoma
      (CMEC) of the mandible was firstly described by Lepp in 1936, on a 66-year-old
      femalepatient. CMEC is characterized by atypical clinical image and radiological
      manifestation. Case Outline: A 55-year-old female patient was examined at the
      Clinic of Dentistry in Nis, Serbia, withanamnestic data regarding the presence of
      painless swelling in the right side of the mandible. Consideringthe
      histopathological results and presence of enlarged lymph nodes, right
      hemimandibulectomyand tumour excision from pterygomandibular space followed by
      supraomohyoid neck dissection wasdone. In due course, postoperative radiotherapy
      was applied (60 Gy) Conclusion: CMEC represents a rare tumor, characterized by
      local tissue destruction and ability to metastasize.Initial biopsy represented
      the key in preoperative planing. Radical excision with neck lymphnode dissection
      followed by postoperative radiotherapy in our case represent a successful method
      oftreating CMEC of the mandible.

PMID- 29653041
TI  - Epithelioid hemangioma in the oral mucosa - A case report.
AB  - Introduction: Epithelioid hemangioma is an uncommon benign vasoproliferative
      neoplasm that usuallymanifests as multiple red nodules in middle-aged adults Case
      Outline: 52-year-old male patient presented with a one-year history of a nodular
      lesion in theleft buccal mucosa measuring 3 cm. The clinical hypothesis was
      lipoma. An excisional biopsy revealed acircumscribed lesion composed of lobules
      of vessels with perceptible or poor lumina, associated with aprominent
      inflammatory infiltrate consisting of eosinophils, histiocytes and chronic
      inflammatory cells.The endothelial cells composing the lesion had an epithelioid
      morphology and contained abundanteosinophilic cytoplasm. Immunohistochemistry for
      CD34, factor VIII, collagen IV, alpha-smooth muscleactin, and mast cells, as well
      as histochemical staining with Weigert's orcein were performed. Conclusion:
      Vascular proliferations of soft tissues are a diverse and morphologically complex
      group oflesions that are difficult to diagnose. This report presents a case of
      oral epithelioid hemangioma, highlightingrelevant morphological and
      immunohistochemical features that could help distinguish thiscondition from other
      neoplasms.

PMID- 29653042
TI  - Symptomatic isolated thoracic splenosis 11 years after abdominal trauma - Case
      report.
AB  - Introduction: Thoracic splenosis is defined as the autotransplantation of splenic
      tissue into thorax. Itoccurs due to splenic rupture in association with a
      diaphragmatic tear on the left side after a traumaticevent. It is a rare disease
      that most commonly remains undiscovered as it is usually asymptomatic. Case
      Outline: We present a symptomatic case of thoracic splenosis in a 53-year-old
      smoker male patientwith a medical history of abdominal surgery and splenectomy
      for a thoracoabdominal gunshot. Threeyears before the medical examination he was
      suffering from dyspnea, frequent coughing, left pleuriticchest pain and
      complained about faster fatigue. A chest radiograph obtained during a medical
      checkupshowed a multinodular left pleura-based mass in the upper lobe.
      Established histopathological diagnosisafter surgical removal of the nodule was
      splenosis. No evidence of malignancy was observed. Conclusion: Splenosis should
      be considered as a differential diagnosis by the undertaken workup of
      leftpulmonary nodules or masses in patients with a history of trauma.

PMID- 29653043
TI  - Single stage surgical treatment of amniotic band syndrome - Case report.
AB  - Introduction: Amniotic band syndrome is a rare congenital disorder with clinical
      presentation of constrictingbands in different parts of extremities or whole
      extremities. Conservative or surgical treatmentis provided depending on the type
      and severity of the anomaly. Case Outline: The paper presents the case of a
      neonate patient with constriction bands localized on theleft leg. During the
      second week of life, a surgery was indicated, and a single-stage multiple Z
      plasty wasperformed to correct the anomalies on the left lower leg. Postoperative
      edema in the distal part of thelower leg was easily managed by incisions and
      drainage. Two months later, the correction of the strictureof the left thigh was
      managed using the same procedure. The postoperative course was uneventful andthe
      outcome was satisfactory after a two-year follow-up. Conclusion: Evaluation of a
      patient with amniotic band syndrome, as well as diagnosis, monitoring,
      treatmentand postoperative care, should always be multidisciplinary. A single
      stage correction approachprovided satisfactory both functional and aesthetic
      results. Given many morphological variations of thesyndrome, a decision on the
      strategy of treatment should be made individually for each patient.

PMID- 29653044
TI  - Benign cystic teratoma of the mesosigmoid - Report of a case.
AB  - Introduction: Extragonadal intraperitoneal teratomas are very rare, especially
      those arising from mesenteryand mesocolon. In the contemporary literature only 22
      cases of such tumors have been publishedand described. Case Outline: We report a
      case of a 52-year-old woman with a benign cystic teratoma of the mesosigmoid.The
      patient presented with mild clinical signs of intestinal obstruction.
      Computerized tomography ofthe pelvis and abdomen showed a large 9.7 * 8.9 * 9.4
      cm calcified tumor in the lower part of the lefthemiabdomen. Extraluminal
      obstruction was verified by colonoscopy at 35 cm from the anal verge.
      Intraoperatively, a cystic calcified tumor of the mesosigmoid was found causing
      extraluminal obstructionof the left colon. The tumor was extirpated and a partial
      resection of the adherent great omentum wasperformed. The histopathological
      examination revealed a benign cystic teratoma. Conclusion: Considering the fact
      that mesenteric teratomas are extremely rare tumors, it is difficult todesignate
      a general conclusion for an adequate treatment of patients suffering from them.
      Completesurgical excision is indicated in order to establish a correct
      histopathological diagnosis and to relievethe patients of symptoms.

PMID- 29653045
TI  - A rare localization of osteoid osteoma - Presentation of two cases.
AB  - Introduction: Osteoid osteoma is a benign osteoid-forming tumor generally
      localized to the long bones,is rarely localized in the hand and the major symptom
      is intermittent pain. This study aims to presenttwo patients who were operated on
      for metacarpal osteoid osteomas. Case Outline: A 16-year-old female patient and
      an 18-year-old male patient were operated on formetacarpal osteoid osteomas. The
      major symptom was intermittent pain for both patients. After surgicalexcision of
      the niduses, the complaints resolved in both cases. Conclusion: In the case of
      high suspicion for osteoid osteoma, computed tomography or magneticresonance
      imaging should be performed due to the risk of negative radiographic findings.
      Surgicalexcision is curative and a safe method of treatment.

PMID- 29653046
TI  - Mechanism of Action of the Cytotoxic Asmarine Alkaloids.
AB  - The asmarines are a family of cytotoxic natural products whose mechanism of
      action is unknown. Here, we used chemical synthesis to reverse engineer the
      asmarines and understand the functions of their individual components. We found
      that the potent asmarine analog "delmarine" arrested the mammalian cell cycle in
      the G1 phase and that both cell cycle arrest and cytotoxicity were rescued by
      cotreatment with ferric and ferrous salts. Cellular iron deprivation was clearly
      indicated by changes in iron-responsive protein markers, and cytotoxicity
      occurred independently of radical oxygen species (ROS) production. Chemical
      synthesis allowed for annotation of the distinct structural motifs required for
      these effects, especially the unusual diazepine, which we found enforced an iron
      binding tautomer without distortion of the NCNO dihedral angle out of plane. With
      this information and a correlation of cytotoxicity with logP, we could replace
      the diazepine by lipophilic group appendage to N9, which avoided steric clash
      with the N6-alkyl required to access the aminopyridine. This study transformed
      the asmarines, scarce marine metabolites, into easily synthesized, modular
      chemotypes that may complement or succeed iron-selective binders in clinical
      trials and use.

PMID- 29653047
TI  - Understanding Electrochemically Activated Persulfate and Its Application to
      Ciprofloxacin Abatement.
AB  - This study offers insight into the roles anodic and cathodic processes play in
      electrochemically activated persulfate (EAP) and screens EAP as a viable
      technique for ciprofloxacin degradation in wastewater. Sulfate radical formation
      at a boron-doped diamond (BDD) anode and persulfate activation at a graphite
      cathode were experimentally elucidated using different electrolytes and
      electrochemical setups. Rapid ciprofloxacin transformation occurred via pseudo
      first-order mechanisms with respect to ciprofloxacin in persulfate electrolyte,
      reaching 84% removal in 120 min using EAP. Transformation pathways were compared
      to those in nitrate and sulfate electrolytes. Ciprofloxacin removal rates in the
      electrochemical system were 88% and 33% faster in persulfate than nitrate and
      sulfate electrolytes, respectively. Total organic carbon removal rates were 93%
      and 48% faster in persulfate than nitrate and sulfate, respectively. Use of
      sulfate electrolyte resulted in removal rates 6-7 times faster than those in
      nitrate solution. Accelerated removal in sulfate was attributed to anodic sulfate
      radical formation, while enhanced removal in persulfate was associated with
      cathodic persulfate activation and nonradical persulfate activation at the BDD
      anode. Quenching experiments indicated both sulfate radicals and hydroxyl
      radicals contributed to degradation. Comparisons between platinum and graphite
      cathodes showed similar cathodic persulfate activation and ciprofloxacin
      degradation.

PMID- 29653048
TI  - Different-Length Hydrazone Activated Polymers for Plasmid DNA Condensation and
      Cellular Transfection.
AB  - The recent advances in genetic engineering demand the development of conceptually
      new methods to prepare and identify efficient vectors for the intracellular
      delivery of different nucleotide payloads ranging from short single-stranded
      oligonucleotides to larger plasmid double-stranded circular DNAs. Although many
      challenges still have to be overcome, polymers hold great potential for
      intracellular nucleotide delivery and gene therapy. We here develop and apply the
      postpolymerization modification of polyhydrazide scaffolds, with different degree
      of polymerization, for the preparation of amphiphilic polymeric vehicles for the
      intracellular delivery of a circular plasmid DNA. The hydrazone formation
      reactions with a mixture of cationic and hydrophobic aldehydes proceed in
      physiologically compatible aqueous conditions, and the resulting amphiphilic
      polyhydrazones are directly combined with the biological cargo without any
      purification step. This methodology allowed the preparation of stable polyplexes
      with a suitable size and zeta potential to achieve an efficient encapsulation and
      intracellular delivery of the DNA cargo. Simple formulations that performed with
      efficiencies and cell viabilities comparable to the current gold standard were
      identified. Furthermore, the internalization mechanism was studied via
      internalization experiments in the presence of endocytic inhibitors and
      fluorescence microscopy. The results reported here confirmed that the
      polyhydrazone functionalization is a suitable strategy for the screening and
      identification of customized polymeric vehicles for the delivery of different
      nucleotide cargos.

PMID- 29653049
TI  - Influence of Cationic Phosphatidylcholine Derivative on Monolayer and Bilayer
      Artificial Bacterial Membranes.
AB  - An increasing number of bacterial infections and the rise in antibiotic
      resistance of a number of bacteria species forces one to search for new
      antibacterial compounds. The latter facts motivate the investigations presented
      herein and are aimed at studying the influence of a cationic lipid, 1-palmitoyl-2
      oleoyl- sn-glycero-3-ethylphosphocholine (EPOPC), on model (mono- and bilayer)
      membranes. The monolayer experiments involved the analysis of the interactions of
      EPOPC with bacterial membrane lipids in one component and mixed systems as well
      as Brewster angle microcopy studies. The properties of liposomes were analyzed
      based on the results of dynamic light scattering (DLS) and zeta potential
      measurements as well as on the experiments concerning the release of calcein
      entrapped in liposomes after titration with surfactant solution and steady-state
      fluorescence anisotropy of DPH. The obtained results evidenced that EPOPC, even
      at low concentrations, strongly changes organization of model systems making them
      less condensed. Moreover, EPOPC decreases the hydrodynamic diameter of liposomes,
      increases their zeta potential, and destabilizes model membranes, increasing
      their fluidity and permeability. Also, the in vitro tests performed on
      Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive)
      strains prove that EPOPC has some bacteriostatic properties which seem to be
      stronger toward Gram-negative than Gram-positive bacteria. All these findings
      allow one to conclude that EPOPC mode of action may be directly connected with
      the interactions of EPOPC molecules with bacterial membranes.

PMID- 29653050
TI  - Dissolution of Complex Metal Oxides from First-Principles and Thermodynamics:
      Cation Removal from the (001) Surface of Li(Ni1/3Mn1/3Co1/3)O2.
AB  - The rapid increase in use of Li-ion batteries in portable electronics has created
      a pressing need to understand the environmental impact and long-term fate of
      electonic waste (e-waste) products such as heavy and/or reactive metals. The type
      of e-waste that we focus on here are the complex metal oxide nanomaterials that
      compose Li-ion battery cathodes. While in operation the complex metal oxides are
      in a hermetically sealed container. However, at the end of life, improper
      disposal can cause structural transformations such as dissolution and metal
      leaching, resulting in a significant exposure risk to the surrounding
      environment. The transformations that occur between operational to environmental
      settings gives rise to a stark knowledge gap between macroscopic design and
      molecular-level behavior. In this study we use theory and modeling to describe
      and explain previously published experimental data for cation release from
      Li(Ni1/3Mn1/3Co1/3)O2 (NMC) nanoparticles in an aqueous environment ( Chem.
      Mater. 2016 (28) 1092-1100). To better understand the transformations that may
      occur when this material is exposed to the environment, we compute the free
      energy of surface dissolution, Delta G, from the complex metal oxide NMC for a
      range of surface terminations and pH.

PMID- 29653051
TI  - On-chip Heaters for Tension Tuning of Graphene Nanodrums.
AB  - For the study and application of graphene membranes, it is essential to have
      means to control their resonance frequency and temperature. Here, we present an
      on-chip heater platform for local tuning of in-plane tension in graphene
      mechanical resonators. By Joule heating of a metallic suspension ring we show
      thermomechanical resonance frequency tuning in a few-layer (FL) graphene
      nanodrum, which is accompanied by an increase in its quality factor, which we
      attribute to the increase of the in-plane tension. The in situ control of
      temperature, in-plane tension, resonance frequency, and quality factor of
      suspended two-dimensional (2D) nanodrums makes this device a unique platform for
      investigating the origin of dissipation in these ultrathin structures and can be
      of fundamental importance for studying the thermal properties of 2D materials.
      Moreover, by simultaneously controlling the heater and the backgate voltage, we
      can independently control the resonance frequency and quality factor, which is of
      great importance for applications in sensors and resonant mechanical filters.

PMID- 29653052
TI  - Resolving the Chemically Discrete Structure of Synthetic Borophene Polymorphs.
AB  - Atomically thin two-dimensional (2D) materials exhibit superlative properties
      dictated by their intralayer atomic structure, which is typically derived from a
      limited number of thermodynamically stable bulk layered crystals (e.g., graphene
      from graphite). The growth of entirely synthetic 2D crystals, those with no
      corresponding bulk allotrope, would circumvent this dependence upon bulk
      thermodynamics and substantially expand the phase space available for structure
      property engineering of 2D materials. However, it remains unclear if synthetic 2D
      materials can exist as structurally and chemically distinct layers anchored by
      van der Waals (vdW) forces, as opposed to strongly bound adlayers. Here, we show
      that atomically thin sheets of boron (i.e., borophene) grown on the Ag(111)
      surface exhibit a vdW-like structure without a corresponding bulk allotrope.
      Using X-ray standing wave-excited X-ray photoelectron spectroscopy, the positions
      of boron in multiple chemical states are resolved with sub-angstrom spatial
      resolution, revealing that the borophene forms a single planar layer that is 2.4
      A above the unreconstructed Ag surface. Moreover, our results reveal that
      multiple borophene phases exhibit these characteristics, denoting a unique form
      of polymorphism consistent with recent predictions. This observation of synthetic
      borophene as chemically discrete from the growth substrate suggests that it is
      possible to engineer a much wider variety of 2D materials than those accessible
      through bulk layered crystal structures.

PMID- 29653053
TI  - Scalable Direct Writing of Lanthanide-Doped KMnF3 Perovskite Nanowires into
      Aligned Arrays with Polarized Up-Conversion Emission.
AB  - The use of one-dimensional nano- and microstructured semiconductor and lanthanide
      materials is attractive for polarized-light-emission studies. Up-conversion
      emission from single-nanorod or anisotropic nanoparticles with a degree of
      polarization has also been discussed. However, microscale arrays of
      nanoparticles, especially well-aligned one-dimensional nanostructures as well as
      their up-conversion polarization characterization, have not been investigated
      yet. Herein, we present a novel and facile paradigm for preparing highly aligned
      arrays of lanthanide-doped KMnF3 (KMnF3:Ln) perovskite nanowires, which are good
      candidates for polarized up-conversion emission studies. These perovskite
      nanowires, with a width of 10 nm and length of a few micrometers, are formed
      through the oriented attachment of KMnF3:Ln nanocubes along the [001] direction.
      By the employment of KMnF3:Ln nanowire gel as nanoink, a direct-writing method is
      developed to obtain diverse types of aligned patterns from the nanoscale to the
      wafer scale. Up-conversion emissions from the highly aligned nanowire arrays are
      polarized along the array direction with a polarization degree up to 60%. Taking
      advantage of microscopic nanowire arrays, these polarized up-conversion emissions
      should offer potential applications in light or information transportation.

PMID- 29653054
TI  - One Enzyme To Build Them All: Ring-Size Engineered Siderophores Inhibit the
      Swarming Motility of Vibrio.
AB  - Bacteria compete for ferric iron by producing siderophores, and some microbes
      engage in piracy by scavenging siderophores of their competitors. The macrocyclic
      hydroxamate siderophore avaroferrin of Shewanella algae inhibits swarming of
      Vibrio alginolyticus by evading this piracy. Avaroferrin, as well as related
      putrebactin and bisucaberin, are produced by the IucC-like synthetases AvbD,
      PubC, and BibCC. Here, we have established that they are capable of synthesizing
      not only their native product but also other siderophores. Exploiting this
      relaxed substrate specificity by synthetic precursors generated 15 different ring
      size engineered macrocycles ranging from 18- to 28-membered rings, indicating
      unprecedented biosynthetic flexibility of the enzymes. Two of the novel
      siderophores could be obtained in larger quantities by precursor-directed
      biosynthesis in S. algae. Both inhibited swarming motility of Vibrio and, similar
      to avaroferrin, the most active one exhibited a heterodimeric architecture. Our
      results demonstrate the impact of minor structural changes on biological
      activity, which may trigger the evolution of siderophore diversity.

PMID- 29653055
TI  - Solid-Phase Nucleic Acid Sequence-Based Amplification and Length-Scale Effects
      during RNA Amplification.
AB  - Solid-phase oligonucleotide amplification is of interest because of possible
      applications to next-generation sequencing, multiplexed microarray-based
      detection, and cell-free synthetic biology. Its efficiency is, however, less than
      that of traditional liquid-phase amplification involving unconstrained primers
      and enzymes, and understanding how to optimize the solid-phase amplification
      process remains challenging. Here, we demonstrate the concept of solid-phase
      nucleic acid sequence-based amplification (SP-NASBA) and use it to study the
      effect of tethering density on amplification efficiency. SP-NASBA involves two
      enzymes, avian myeloblastosis virus reverse transcriptase (AMV-RT) and RNase H,
      to convert tethered forward and reverse primers into tethered double-stranded DNA
      (ds-DNA) bridges from which RNA- amplicons can be generated by a third enzyme, T7
      RNA polymerase. We create microgels on silicon surfaces using electron-beam
      patterning of thin-film blends of hydroxyl-terminated and biotin-terminated
      poly(ethylene glycol) (PEG-OH, PEG-B). The tethering density is linearly related
      to the PEG-B concentration, and biotinylated primers and molecular beacon
      detection probes are tethered to streptavidin-activated microgels. While SP-NASBA
      is very efficient at low tethering densities, the efficiency decreases
      dramatically with increasing tethering density due to three effects: (a) a
      reduced hybridization efficiency of tethered molecular beacon detection probes;
      (b) a decrease in T7 RNA polymerase efficiency;

PMID- 29653056
TI  - UV Photolysis of Chloramine and Persulfate for 1,4-Dioxane Removal in Reverse
      Osmosis Permeate for Potable Water Reuse.
AB  - A sequential combination of membrane treatment and UV-based advanced oxidation
      processes (UV/AOP) has become the industry standard for potable water reuse.
      Chloramines are used as membrane antifouling agents and therefore carried over
      into the UV/AOP. In addition, persulfate (S2O82-) is an emerging oxidant that can
      be added into a UV/AOP, thus creating radicals generated from both chloramines
      and persulfate for water treatment. This study investigated the simultaneous
      photolysis of S2O82- and monochloramine (NH2Cl) on the removal of 1,4-dioxane
      (1,4-D) for potable-water reuse. The dual oxidant effects of NH2Cl and S2O82- on
      1,4-D degradation were examined at various levels of oxidant dosage, chloride,
      and solution pH. Results showed that a NH2Cl-to-S2O82- molar ratio of 0.1 was
      optimal, beyond which the scavenging by NH2Cl of HO*, SO4*-, and Cl2*- radicals
      decreased the 1,4-D degradation rate. At the optimal ratio, the degradation rate
      of 1,4-D increased linearly with the total oxidant dose up to 6 mM. The combined
      photolysis of NH2Cl and S2O82- was sensitive to the solution pH due to a
      disproportionation of NH2Cl at pH lower than 6 into less-photoreactive
      dichloramine (NHCl2) and radical scavenging by NH4+. The presence of chloride
      transformed HO* and SO4*- to Cl2*- that is less-reactive with 1,4-D, while the
      presence of dissolved O2 promoted gaseous nitrogen production. Results from this
      study suggest that the presence of chloramines can be beneficial to persulfate
      photolysis in the removal of 1,4-D; however, the treatment efficiency depends on
      a careful control of an optimal NH2Cl dosage and a minimal chloride residue.

PMID- 29653057
TI  - Charge-State-Dependent Variation of Signal Intensity Ratio between Unbound
      Protein and Protein-Ligand Complex in Electrospray Ionization Mass Spectrometry:
      The Role of Solvent-Accessible Surface Area.
AB  - Native electrospray ionization mass spectrometry (ESI-MS) is nowadays widely used
      for the direct and sensitive determination of protein complex stoichiometry and
      binding affinity constants ( Ka). A common yet poorly understood phenomenon in
      native ESI-MS is the difference between the charge-state distributions (CSDs) of
      the bound protein-ligand complex (PL) and unbound protein (P) signals. This
      phenomenon is typically attributed to experimental artifacts such as nonspecific
      binding or in-source dissociation and is considered highly undesirable, because
      the determined Ka values display strong variation with charge state. This
      situation raises serious concerns regarding the reliability of ESI-MS for the
      analysis of protein complexes. Here we demonstrate that, contrary to the common
      belief, the CSD difference between P and PL ions can occur without any loss of
      complex integrity, simply due to a change in the solvent-accessible surface area
      (DeltaSASA) of the protein upon ligand binding in solution. The experimental CSD
      shifts for PL and P ions in ESI-MS are explained in relation to the magnitude of
      DeltaSASA for diverse protein-ligand systems using a simple model based on the
      charged residue mechanism. Our analysis shows that the revealed DeltaSASA factor
      should be considered rather general and be given attention for the correct
      spectral interpretation of protein complexes.

PMID- 29653058
TI  - Heart Variability Biofeedback as Supplementary Care for Brain Cancer: A
      Feasibility Study.

PMID- 29653059
TI  - Re: "In Pursuit of the Most Cost-Effective Pediatric Laparoscopic Appendectomy:
      The Effect of Disposable Instrument Choice on Operative Time and Surgeon
      Controllable Cost" (J Laparoendosc Adv Surg Tech A 2017;27:1309-1313).

PMID- 29653060
TI  - Tree-Related Injuries Associated With Response and Recovery From Hurricane Sandy,
      New Jersey, 2011-2014.
AB  - OBJECTIVES: Extreme weather events require extensive tree removal and disposal,
      tasks associated with severe injury risks among workers and residents. To help
      understand the risks of such activities, we evaluated the impact of a large and
      destructive storm (Hurricane Sandy in 2012) on the incidence of tree-related
      injuries. METHODS: We searched chief-complaint text fields for patients aged 18
      65 from 2011-2014 emergency department visit records submitted by New Jersey
      hospitals through the state-based syndromic surveillance system. Tree-related
      keywords (eg, saw, branch, wood chip, woodchip, tree) identified possible
      injuries that we then reviewed to exclude unrelated cases and classify mechanisms
      of tree-related injury. We used Poisson regression analysis to evaluate changes
      in the rates of probable tree-related injuries, adjusting for total emergency
      department visits and seasonal variation. RESULTS: We identified 698 probable
      tree-related injuries from 2011-2014 among patients aged 18-65, including 104
      (14.9%) falls, 241 (34.5%) machine-related injuries, 311 (44.6%) struck-by
      injuries, and 42 (6.0%) other tree-related injuries. Tree-related injuries
      increased significantly in the quarter immediately after Hurricane Sandy
      (November 2012-January 2013) compared with the same quarter the year before (rate
      ratio [RR] = 1.67; 95% confidence interval [CI], 1.13-2.47) and the year after
      (RR = 2.47; 95% CI, 1.62-3.78) Hurricane Sandy, especially for struck-by injuries
      compared with the year before (RR = 2.74; 95% CI, 1.47-5.12) and the year after
      (RR = 4.17; 95% CI, 2.09-8.32) Hurricane Sandy. More than one-third of the
      injuries (33.4%) involved chainsaws. CONCLUSIONS: A major hurricane was
      associated with an increase in tree-related injuries in emergency departments,
      especially for mechanisms consistent with handling downed and damaged trees.
      Further research should confirm these findings and evaluate opportunities for
      preventing tree-related injuries.

PMID- 29653061
TI  - To t-Test or Not to t-Test? A p-Values-Based Point of View in the Receiver
      Operating Characteristic Curve Framework.
AB  - A common statistical doctrine supported by many introductory courses and
      textbooks is that t-test type procedures based on normally distributed data
      points are anticipated to provide a standard in decision-making. In order to
      motivate scholars to examine this convention, we introduce a simple approach
      based on graphical tools of receiver operating characteristic (ROC) curve
      analysis, a well-established biostatistical methodology. In this context, we
      propose employing a p-values-based method, taking into account the stochastic
      nature of p-values. We focus on the modern statistical literature to address the
      expected p-value (EPV) as a measure of the performance of decision-making rules.
      During the course of our study, we extend the EPV concept to be considered in
      terms of the ROC curve technique. This provides expressive evaluations and
      visualizations of a wide spectrum of testing mechanisms' properties. We show that
      the conventional power characterization of tests is a partial aspect of the
      presented EPV/ROC technique. We desire that this explanation of the EPV/ROC
      approach convinces researchers of the usefulness of the EPV/ROC approach for
      depicting different characteristics of decision-making procedures, in light of
      the growing interest regarding correct p-values-based applications.

PMID- 29653062
TI  - Reducing the Risk of Alzheimer's Disease and Maintaining Brain Health in an Aging
      Society.

PMID- 29653063
TI  - Functional Evaluation of ZNF350 Missense Genetic Variants Associated with Breast
      Cancer Susceptibility.
AB  - ZNF350, a BRCA1-interacting protein, could mediate BRCA1-induced sequence
      specific transcriptional repression of several genes, including GADD45alpha. As a
      potential breast cancer susceptibility gene, single nucleotide polymorphisms
      (SNPs), especially missense SNPs, may influence the transcriptional repression of
      its target tumor suppressor genes and individuals' breast cancer risk. Using the
      gene-based haplotype-tagging SNPs strategy, we evaluated the association between
      six ZNF350 polymorphisms and breast cancer risk in a case-control set from a
      northern Chinese population. The impact of ZNF350 variations on transcriptional
      repression of GADD45alpha was also examined. It was found that ZNF350 rs2278420
      (L66P) and rs2278415 (S501R) missense genetic variants are in complete linkage
      disequilibrium and have a significant impact on inter-individual susceptibility
      to breast cancer. Additionally, ZNF350 GGCGT or GGCGC haplotype is also
      associated with a significantly increased breast cancer risk compared with the
      GGCAC haplotype. ZNF350 L66P variant modifies the risk of breast cancer not only
      by itself but also in a gene-environment interaction manner with age, age at
      menarche, menopause status, or estrogen receptor status. Interestingly, we
      observed that ZNF350 L66P and S501R SNPs could weaken the capability of ZNF350
      mediated GADD45alpha transcription repression and it may be an underlying
      mechanism of the observed epidemiological associations. Our results highlight
      ZNF350 as an important gene in human mammary oncogenesis and ZNF350 missense
      genetic polymorphisms confer susceptibility to breast cancer.

PMID- 29653064
TI  - Longitudinal Evaluation of Quality Improvement and Public Health Accreditation
      Readiness in Nebraska Local Health Departments, 2011-2016.
AB  - OBJECTIVES: Public health accreditation is intended to improve the performance of
      public health departments, and quality improvement (QI) is an important component
      of the Public Health Accreditation Board process. The objective of this study was
      to evaluate the QI maturity and accreditation readiness of local health
      departments (LHDs) in Nebraska during a 6-year period that included several
      statewide initiatives to progress readiness, including funding and technical
      assistance. METHODS: We used a mixed-methods approach that consisted of both
      online surveys and key informant interviews to assess QI maturity and
      accreditation readiness. Nineteen of Nebraska's 21 LHDs completed the survey in
      2011 and 2013, 20 of 20 LHDs completed the survey in 2015, and 19 of 20 LHDs
      completed the survey in 2016. We facilitated a large group discussion with staff
      members from 16 LHDs in 2011, and we conducted key informant interviews with
      staff members from 4 LHDs in 2015. RESULTS: Both QI maturity and accreditation
      readiness improved from 2011 to 2016. In 2011, of 19 LHDs, only 6 LHD directors
      agreed that their LHD had a culture that focused on QI, but this number increased
      every year up to 12 in 2016. The number of LHDs that had a high capacity to
      engage in QI efforts improved from 3 in 2011 to 8 in 2016. The number of LHDs
      with a QI plan increased from 3 in 2011 to 10 in 2016. The number of LHDs that
      were confident in their ability to obtain Public Health Accreditation Board
      accreditation improved from 6 in 2011 to 13 in 2016. Although their QI maturity
      generally increased over time, LHDs interviewed in 2015 still faced challenges
      adopting a formal QI system. External financial and technical support helped LHDs
      build their QI maturity and accreditation readiness. CONCLUSION: Funding and
      technical assistance can improve LHDs' QI maturity and accreditation readiness.
      Improvement takes time and sustained efforts by LHDs, and support from external
      partners (eg, state health departments) helps build LHDs' QI maturity and
      accreditation readiness.

PMID- 29653066
TI  - Early Chronic Obstructive Pulmonary Disease or Early Detection of Mild Disease?

PMID- 29653065
TI  - TET2: A Novel Epigenetic Regulator and Potential Intervention Target for
      Atherosclerosis.
AB  - Atherosclerosis is the underlying cause of cardio-cerebrovascular disease.
      However, the mechanisms of atherosclerosis are still unclear. The modification of
      DNA methylation has an important role in atherosclerosis development. As a member
      of the Ten-eleven translocation (TET) family, TET methylcytosine dioxygenase 2
      (TET2) can modify DNA methylation by catalyzing 5-methylcytosine to 5
      hydroxymethylcytosine and mediate DNA demethylation. Recent findings suggest that
      TET2 is related to the phenotype transformation of vascular smooth muscle cells,
      endothelial dysfunction, and inflammation of macrophage, the key factors of
      atherosclerosis. Therefore, TET2 may be a potential target for atherosclerosis
      treatment. This review will elaborate the recent findings that suggest the role
      of TET2 in atherosclerosis.

PMID- 29653067
TI  - Who is willing to come back? College students' willingness to seek help after
      using campus mental health services.
AB  - OBJECTIVE: To examine characteristics of college students who have previously
      received mental health (MH) services on campus and are willing to seek help again
      in the future. PARTICIPANTS: Spring 2015 ACHA-NCHA II (N = 12,501) undergraduate
      respondents who had previously used MH services on their current campus. METHODS:
      Binary logistic regression with willingness to seek MH services in the future as
      the dependent variable. RESULTS: Among students who had already utilized campus
      MH services, significant predictors for future help-seeking were: female, white,
      gay/lesbian, those not working for pay, having the college/university health
      insurance plan, and not currently/previously serving in the military (p < .05).
      CONCLUSIONS: The predictors for willingness to use services in the future were
      consistent with the existing literature related to initial use. Colleges and
      universities need to consider factors that influence openness to MH services
      after a previous experience in addition to initiating care. Implications for
      college MH professionals are provided.

PMID- 29653068
TI  - Variation in Birth Outcomes by Mother's Country of Birth Among Hispanic Women in
      the United States, 2013.
AB  - OBJECTIVES: Despite knowledge that the Hispanic population is growing in the
      United States and that birth outcomes may vary by maternal country of birth, data
      on birth outcomes by maternal country of birth among Hispanic women are scant. We
      compared the rates of 3 birth outcomes for infants born in the United States
      preterm birth, low birth weight, and small for gestational age-between foreign
      born Hispanic women and US-born Hispanic women, and then we examined these birth
      outcomes by mother's country of birth for foreign-born Hispanic women. METHODS:
      Using the 2013 natality file from the National Vital Statistics System of the
      National Center for Health Statistics, we examined data on the 3 birth outcomes
      and maternal characteristics by maternal country of birth. We used log binomial
      models to calculate unadjusted and adjusted relative risks for preterm birth, low
      birth weight, and small for gestational age for US-born Hispanic women compared
      with foreign-born Hispanic women. We also compared the relative risk of each
      adverse birth outcome for foreign-born Hispanic women by country of birth.
      RESULTS: US-born Hispanic women had higher rates of the 3 birth outcomes than did
      foreign-born Hispanic women (preterm birth: 8.0% vs 7.0%; low birth weight: 6.1%
      vs 5.2%; small for gestational age: 9.2% vs 7.9%). These higher rates persisted
      after adjusting for maternal characteristics. The rates for these 3 birth
      outcomes varied significantly by country of birth for foreign-born Hispanic
      women, with Puerto Rican women consistently having the poorest birth outcomes.
      CONCLUSIONS: Our results demonstrated heterogeneity in rates of adverse birth
      outcomes by country of birth for foreign-born Hispanic women. Presenting rates
      for foreign-born mothers as a group masks differences by country. To understand
      possible changes in data on birth outcomes, states should stratify data by
      maternal country of birth.

PMID- 29653069
TI  - Breathing Exercises Must Be a Real and Effective Intervention to Consider in
      Women with Fibromyalgia: A Pilot Randomized Controlled Trial.
AB  - BACKGROUND/OBJECTIVE: Respiratory problems can aggravate pain located in the
      coincident areas with tender points in the upper half of the body in patients
      with fibromyalgia (FM) and easily become fatigued, thus can lead to a decrease in
      the functionality of daily activities. The purpose of this study was to examine
      the effects of a breathing exercises program on pain thresholds tolerance on
      tender points and FM impact on daily life. METHODS/DESIGN: Thirty-five women with
      FM (age 34-67 years) were randomly assigned to an exercise group (n = 18),
      performing breathing exercises (30 min/session, 7 times/week; for 12 weeks), or
      to a control group (n = 17). Pain thresholds tolerance on tender points were
      measured by the physician using digital pressure algometer and FM impact on daily
      life was evaluated with the Portuguese version of the Fibromyalgia Impact
      Questionnaire (FIQ). RESULTS: After 12 weeks of breathing exercises significant
      improvements were observed in the mean values of the treatment effects on pain
      thresholds tolerance on tender points and in the functional capacity to perform
      daily life, pain, and fatigue in favor of the exercise group. Gains in second
      rib, occiput, and supraspinatus pairs of the tender points predict improvements
      in the functional capacity, pain, and fatigue. CONCLUSION: Our study demonstrated
      that breathing exercises produced relevant benefits on pain thresholds tolerance
      on tender points located in the upper half of the body, some of which predicted
      improvements in the impact of FM in the functional capacity to perform daily
      life, pain, and fatigue. These results provide further support of an idea that
      breathing exercises are a real and effective intervention to consider in women
      with FM. TRIAL REGISTRATION: International Standard Randomized Controlled Trial
      Number ISRCTN37081460, available information in www.isrctn.com/ ISRCTN37081460.

PMID- 29653070
TI  - Comparative Cytogenetics Analysis on Five Genera of Thorny Catfish (Siluriformes,
      Doradidae): Chromosome Review in the Family and Inferences About Chromosomal
      Evolution Integrated with Phylogenetic Proposals.
AB  - Doradidae has been a target of phylogenetic studies over the last few years, but
      chromosomal information about the family is still scarce. Therefore, new
      cytogenetic data are provided herein and they are correlated with phylogenetic
      proposals to contribute to the knowledge of chromosomal evolution within
      doradids. Cytogenetic studies were performed on Trachydoras paraguayensis,
      Anadoras sp. "araguaia," Ossancora eigenmanni, Platydoras armatulus, and
      Rhinodoras dorbignyi. O. eigenmanni, P. armatulus, and R. dorbignyi had 2n = 58
      chromosomes as found for most doradids, but T. paraguayensis and Anadoras sp.
      "araguaia" had 2n = 56 chromosomes, probably caused by a chromosomal reduction.
      There is a great maintenance of 2n = 58 verified in doradids, but karyotype
      formulas are diverse. Moreover, other markers (i.e., nucleolar organizer regions,
      heterochromatin distribution, and 5S and 18S rDNA) showed a great diversity among
      the analyzed species. Contrasting the variability in the chromosomal markers with
      the maintenance of diploid number, it is likely that inversions and
      translocations played an important role in chromosome differentiation in
      Doradidae. Herein, we created an integrative discussion linking cytogenetic data
      to phylogenetic proposals, based on morphological and genetic features, enabling
      us to identify possible cytogenetic traits, as well as probable chromosomal
      plesiomorphy and apomorphy of Doradidae species.

PMID- 29653071
TI  - Geomorphology Influencing the Diversification of Fish in Small-Order Rivers of
      Neighboring Basins.
AB  - The current analysis investigates whether the uplift of the Serra da Esperanca
      and the Ponta Grossa Arch in the Serra Geral resulted in ichthyofaunistic changes
      in adjacent basins. For this, we describe the phylogeographic structure among
      populations of Trichomycterus collected in hydrographic basins in southern Brazil
      by using partial nucleotide sequences of the mitochondrial gene Cytochrome C
      Oxidase subunit I. Analyses revealed that the nomenclature Trichomycterus davisi
      fails to contain the whole genetic diversity range found in the collected
      specimens and indicates at least six genetic lineages in Trichomycterus.
      Diagnostic morphological characteristics not associated to T. davisi could be
      identified in some specimens from the Iguacu Piquiri haplogroup, indicating the
      occurrence of species Trichomycterus stawiarski. The lack of morphological
      differences among the other clades clearly suggests a cryptic species case.
      Molecular analyses revealed at least five new species besides T. davisi in the
      hydrographic basins and support the interpretation that genetic structure in T.
      davisi species complex is explained by tectonic events intrinsic to the areas of
      influence of Serra da Esperanca and the Ponta Grossa Arch which occurred around
      1.7 My.

PMID- 29653072
TI  - ZebraPace: An Open-Source Method for Cardiac-Rhythm Estimation in Untethered
      Zebrafish Larvae.
AB  - For the assessment of cardiac function, heartbeat represents one key parameter.
      Current methods of heartbeat measurements in the zebrafish larvae usually require
      larval immobilization, fluorescent transgenic strains and a confocal microscope,
      costly commercial software for analysis, or strong programming skills if the
      software is open-source. Here, we present a simple yet powerful method of
      heartbeat analysis using untethered, unlabeled zebrafish larva using ImageJ (open
      source software), which does not require programming skills. We named it as
      ZebraPace for Zebrafish Precise Algorithm for Cardiac-rhythm Estimation.
      ZebraPace works directly with AVI videos and requires no image processing steps.
      ZebraPace uses pixel intensity change in a grayscale video to count the number of
      beats. We have validated the ZebraPace method by pharmacological alterations of
      the heartbeat in zebrafish larvae of 48 and 72 hpf stages. We have also
      determined beat-to-beat interval, which relates to rhythmicity of heartbeat. The
      results obtained by using ZebraPace corroborates well with the heartbeat values
      previously reported for similarly aged larvae as determined by using specialized
      software. We believe that the ZebraPace method is simple, cost-effective, and
      easy to grasp as it involves fewer steps. It not only reduces the manual workload
      but also eliminates sample preparation time and researcher subjectivity.

PMID- 29653073
TI  - A Zebrafish Heart Failure Model for Assessing Therapeutic Agents.
AB  - Heart failure is a leading cause of death and the development of effective and
      safe therapeutic agents for heart failure has been proven challenging. In this
      study, taking advantage of larval zebrafish, we developed a zebrafish heart
      failure model for drug screening and efficacy assessment. Zebrafish at 2 dpf
      (days postfertilization) were treated with verapamil at a concentration of 200
      MUM for 30 min, which were determined as optimum conditions for model
      development. Tested drugs were administered into zebrafish either by direct
      soaking or circulation microinjection. After treatment, zebrafish were randomly
      selected and subjected to either visual observation and image acquisition or
      record videos under a Zebralab Blood Flow System. The therapeutic effects of
      drugs on zebrafish heart failure were quantified by calculating the efficiency of
      heart dilatation, venous congestion, cardiac output, and blood flow dynamics. All
      8 human heart failure therapeutic drugs (LCZ696, digoxin, irbesartan, metoprolol,
      qiliqiangxin capsule, enalapril, shenmai injection, and hydrochlorothiazide)
      showed significant preventive and therapeutic effects on zebrafish heart failure
      (p < 0.05, p < 0.01, and p < 0.001) in the zebrafish model. The larval zebrafish
      heart failure model developed and validated in this study could be used for in
      vivo heart failure studies and for rapid screening and efficacy assessment of
      preventive and therapeutic drugs.

PMID- 29653074
TI  - Routine pacifier use in infants: pros and cons.

PMID- 29653076
TI  - E4bp4 regulates carboxylesterase 2 enzymes through repression of the nuclear
      receptor Rev-erbalpha in mice.
AB  - Carboxylesterases (CES) are a family of phase I enzymes that play an important
      role in xenobiotic clearance and lipid metabolism. Here, we investigate a
      potential role of E4 promoter-binding protein 4 (E4bp4) in regulation of Ces and
      CPT-11 (irinotecan, a first-line drug for treating colorectal cancer)
      pharmacokinetics in mice. Mouse hepatoma Hepa-1c1c7 cells were transfected with
      Rev-erbalpha expression plasmid or siRNA targeting E4bp4. The relative mRNA and
      protein levels of Ces enzymes in the cells or the livers of wild-type and E4bp4
      deficient (E4bp4-/-) mice were determined by qPCR and Western blotting,
      respectively. Transcriptional regulation of Ces by E4bp4/Rev-erbalpha were
      investigated using luciferase reporter, mobility shift, and co
      immunoprecipitation (Co-IP) assays. Pharmacokinetic studies were performed with
      wild-type and E4bp4-/- mice after intraperitoneal injection of CPT-11. E4bp4
      ablation down-regulated an array of hepatic Ces genes in mice. E4bp4-/- mice also
      showed reduced Ces-mediated metabolism and elevated systemic exposure of CPT-11,
      a well-known Ces substrate. Consistently, E4bp4 knockdown reduced the expression
      of Ces genes (Ces2b, Ces2e and Ces2f) in Hepa-1c1c7 cells. Furthermore, Rev
      erbalpha repressed the transcription of Ces2b, whereas E4bp4 antagonized this
      repressive action. Co-IP experiment confirmed a direct interaction between E4bp4
      and Rev-erbalpha. Through a combination of promoter analysis and mobility shift
      assays, we demonstrated that Rev-erbalpha trans-repressed Ces (Ces2b) through its
      specific binding to the -767 to-754 bp promoter region. In conclusion, E4bp4
      regulates Ces enzymes through inhibition of the transrepression activity of Rev
      erbalpha, thereby impacting the metabolism and pharmacokinetics of Ces
      substrates.

PMID- 29653075
TI  - Inhibition of semicarbazide-sensitive amine oxidase reduces atherosclerosis in
      apolipoprotein E-deficient mice.
AB  - Inflammation, oxidative stress, and formation of advanced glycated end products
      (AGEs) and advanced lipoxidation end products (ALEs) are important for
      atherosclerosis. Vascular adhesion protein-1 (VAP-1) participates in inflammation
      and has semicarbazide-sensitive amine oxidase (SSAO) activity, which catalyzes
      oxidative deamination to produce hydrogen peroxide and aldehydes, leading to
      generation of AGEs and ALEs. However, the effect of VAP-1/SSAO inhibition on
      atherosclerosis remains controversial, and no studies used coronary angiography
      to evaluate if plasma VAP-1/SSAO is a biomarker for coronary artery disease
      (CAD). Here, we examined if plasma VAP-1/SSAO is a biomarker for CAD diagnosed by
      coronary angiography in humans and investigated the effect of VAP-1/SSAO
      inhibition by a specific inhibitor PXS-4728A on atherosclerosis in cell and
      animal models. In the study, VAP-1/SSAO expression was increased in plaques in
      humans and in apolipoprotein E (ApoE)-deficient mice, and colocalized with
      vascular endothelial cells and smooth muscle cells (SMCs). Patients with CAD had
      higher plasma VAP-1/SSAO than those without CAD. Plasma VAP-1/SSAO was positively
      associated with the extent of CAD. In ApoE-deficient mice, VAP-1/SSAO inhibition
      reduced atheroma and decreased oxidative stress. VAP-1/SSAO inhibition attenuated
      the expression of adhesion molecules, chemoattractant proteins, and
      proinflammatory cytokines in the aorta, and suppressed monocyte adhesion and
      transmigration across human umbilical vein endothelial cells. Consequently, the
      expression of markers for macrophage recruitment and activation in plaques was
      decreased by VAP-1/SSAO inhibition. Besides, VAP-1/SSAO inhibition suppressed
      proliferation and migration of A7r5 SMC. Our data suggest that plasma VAP-1/SSAO
      is a novel biomarker for the presence and the extent of CAD in humans. VAP-1/SSAO
      inhibition by PXS-4728A is a potential treatment for atherosclerosis.

PMID- 29653077
TI  - Binder of Sperm Proteins protect ram spermatozoa from freeze-thaw damage.
AB  - Cryopreservation causes sub-lethal damage which limits the fertility of frozen
      thawed spermatozoa. Seminal plasma has been investigated as a cryoprotectant, but
      has yielded inconsistent results due to considerable variation in its
      constituents. Individual seminal plasma proteins offer an ideal alternative to
      whole seminal plasma, and several have been correlated with freezing success.
      Binder of Sperm Proteins (BSPs) are abundant ram seminal plasma proteins which
      have been suggested to have significant protective effects on ram spermatozoa
      during cold shock. This is in direct opposition to bull spermatozoa, where BSPs
      cause sperm deterioration during in vitro handling. We investigated the potential
      of BSP1 and BSP5 to prevent freezing associated damage to important functional
      parameters of ram spermatozoa. BSPs purified by size exclusion chromatography
      improved post thaw motility and penetration through artificial mucus. Highly
      purified BSP1 and BSP5, isolated by gelatin affinity and RP-HPLC, improved
      motility and membrane integrity, and reduced post thaw protein tyrosine
      phosphorylation. Exposure to BSP5 before freezing increased the amount of
      phosphatidylethanolamine on the sperm surface after thawing. Neither BSP1 nor
      BSP5 prevented freezing associated changes in membrane lipid disorder. These
      results suggest that BSPs may significantly improve freezing outcomes of ram
      spermatozoa.

PMID- 29653078
TI  - Characterization of CyrI, the hydroxylase involved in the last step of
      cylindrospermopsin biosynthesis: Binding studies, site-directed mutagenesis and
      stereoselectivity.
AB  - Cylindrospermopsin, a cytotoxin from cyanobacteria, is biosynthesized by a
      complex pathway, which involves CyrI, an iron and 2-oxoglutarate dependent
      hydroxylase that transforms 7-deoxy-cylindrospermopsin into cylindrospermopsin
      and its epimer, 7-epi-cylindrospermopsin, in the last step. The activity of CyrI
      from Oscillatoria sp. PCC 7926 depends on Fe(II) (Km = 2.1 MUM), and 2
      oxoglutarate (Km = 3.2 MUM), and is strongly inhibited by 7-deoxy
      cylindrospermopsin at concentration higher than 1 MUM. Using tryptophan
      fluorescence, we measured the binding to CyrI of Fe(II) (KD = 0.02 MUM) and 2
      oxoglutarate (KD = 53 MUM and KD = 1.1 MUM in the absence or presence of 10 MUM
      Fe(II), respectively). The Oscillatoria sp. PCC 6506 CyrI mutants H157A, D159A,
      H247A, and R257A were all inactive, and impaired in the binding of Fe(II) or 2
      oxoglutarate, confirming the identity of the iron ligands and the role of R257 in
      the binding of 2-oxoglutarate. We constructed several chimeric enzymes using the
      Oscillatoria sp. PCC 7926 CyrI protein (stereoselective) and that from
      Oscillatoria sp. PCC 6506 (not stereoselective) to help understanding the
      structural factors that influence the stereoselectivity of the hydroxylation. Our
      data suggest that a predicted alpha-helix in CyrI (positions 87-108) seems to
      modulate the stereoselectivity of the reaction.

PMID- 29653079
TI  - Dominant and sensitive control of oxidative flux by the ATP-ADP carrier in human
      skeletal muscle mitochondria: Effect of lysine acetylation.
AB  - The adenine nucleotide translocase (ANT) of the mitochondrial inner membrane
      exchanges ADP for ATP. Mitochondria were isolated from human vastus lateralis
      muscle (n = 9). Carboxyatractyloside titration of O2 consumption rate (Jo) at
      clamped [ADP] of 21 MUM gave ANT abundance of 0.97 +/- 0.14 nmol ANT/mg and a
      flux control coefficient of 82% +/- 6%. Flux control fell to 1% +/- 1% at
      saturating (2 mM) [ADP]. The KmADP for Jo was 32.4 +/- 1.8 MUM. In terms of the
      free (-3) ADP anion this KmADP was 12.0 +/- 0.7 MUM. A novel luciferase-based
      assay for ATP production gave KmADP of 13.1 +/- 1.9 MUM in the absence of ATP
      competition. The free anion KmADP in this case was 2.0 +/- 0.3 MUM. Targeted
      proteomic analyses showed significant acetylation of ANT Lysine23 and that ANT1
      was the most abundant isoform. Acetylation of Lysine23 correlated positively with
      KmADP, r = 0.74, P = 0.022. The findings underscore the central role played by
      ANT in the control of oxidative phosphorylation, particularly at the energy
      phosphate levels associated with low ATP demand. As predicted by molecular
      dynamic modeling, ANT Lysine23 acetylation decreased the apparent affinity of ADP
      for ANT binding.

PMID- 29653080
TI  - Surgical Treatment of Native and Prosthetic Aortic Infection With Xenopericardial
      Tube Grafts.
AB  - BACKGROUND: The study sought to report our results of surgical treatment of
      native and prosthetic aortic infection with xenopericardial tube grafts from the
      ascending aorta to beyond the bifurcation. METHODS: Within a 28-month period, 20
      patients were treated with a bovine self-made pericardial tube graft to replace
      infected vascular grafts (after conventional surgical aortic replacement or
      endovascular stent graft implantation) or to treat a contaminated surgical site.
      An integrated standardized therapeutic concept was applied in all patients,
      consisting of complete removal of the infected prosthetic material, extensive
      debridement, and orthotopic vascular reconstruction with self-made tube grafts
      constructed from a bovine pericardial patch. RESULTS: Four patients died
      perioperatively (20%) due to sepsis, pulmonary failure, or sudden circulatory
      arrest. The mean follow-up was 18 months (first quartile 2, third quartile 17
      months). Interval computed tomography scans revealed 100% freedom from proven
      aortic reinfection, but reinfection cannot be ruled out in 4 patients who died of
      unknown causes during follow-up or because of ongoing sepsis. Three patients
      required aortic reintervention for a suture-line aneurysm, for graft occlusion,
      and for the development of a neoaortointestinal fistulation, respectively.
      CONCLUSIONS: Patients with infectious aortic disease present in a frail state and
      the initial and the late mortality is substantial. Yet, surgical treatment of
      native and prosthetic aortic infection with xenopericardial tube grafts shows
      promising short-term results with regard to durability and freedom from
      reinfection in any aortic segment. Further studies are needed to learn of the
      long-term behavior of these grafts.

PMID- 29653081
TI  - Need for Pulmonary Arterioplasty During Glenn Independently Predicts Inferior
      Surgical Outcome.
AB  - BACKGROUND: Bidirectional cavopulmonary anastomosis (BDCA) can be accomplished
      with low morbidity and mortality. The impact of concomitant pulmonary
      arterioplasty (PAplasty) is not known. We hypothesized that the need for and
      extent of PAplasty adversely affect BDCA outcomes. METHODS: Patients who
      underwent BDCA at our institution between 2006 and 2014 were included. Patient
      demographics, operative characteristics, mortality, and morbidity were analyzed.
      Serious physiologic adverse event following Glenn (GAE) was defined as need for
      extracorporeal support, BDCA takedown or percutaneous intervention during same
      admission, hospital length of stay 1 SD or more from mean, or need for
      supplemental oxygen at discharge. PAplasty was categorized according to extent.
      Data were analyzed using SAS 9.4 (SAS Institute, Cary, NC). RESULTS: A total of
      424 patients (231 boys, 54%) underwent BDCA for single ventricle physiology at a
      median of 7 (5.5 to 8.9) months of age and 6.5 (5.7 to 7.7) kg weight. A total of
      112 (26%) patients required PAplasty: 23 were patch closures of the divided
      distal PA (type 1), 45 were central PA augmentations (type 2), 23 extended to the
      hilum on 1-branch PA (type 3), and 21 were bilateral hilum to hilum augmentation
      (type 4). Patients who required PAplasty tended to be significantly younger and
      more likely to have single right ventricles. There was no difference in PA
      pressure or resistance between patients who did and did not require PAplasty.
      Major Society of Thoracic Surgeons morbidity (13% vs 6%; p = 0.001), GAE (45% vs
      34%; p = 0.04), and in-hospital mortality (5.4% vs 1.9%; p = 0.03) were higher in
      patients who required PAplasty compared with those who did not. Among the
      operative variables evaluated, need for PAplasty (hazard ratio [HR], 1.6; p =
      0.03) independently predicted hospital mortality. Need for circulatory arrest
      (HR, 4; p = 0.005) and PAplasty (HR, 2.4; p = 0.0006) were independent predictors
      of Society of Thoracic Surgeons morbidity and need for PAplasty independently
      predicted GAE (HR, 1.8; p = 0.03). CONCLUSIONS: The need for PAplasty at BDCA is
      an independent predictor of mortality and morbidity. It is important to consider
      this variable when developing outcome metrics for BDCA.

PMID- 29653082
TI  - Inhibition of glycogen synthase kinase-3 reduces extension of the axonal leading
      process by destabilizing microtubules in cerebellar granule neurons.
AB  - Recent studies have uncovered various molecules that play key roles in neuronal
      morphogenesis. Nevertheless, the mechanisms underlying the neuron-type-dependent
      regulation of morphogenesis remain unknown. We have previously reported that
      inhibition of glycogen synthase kinase-3 (GSK3) markedly reduced axonal length of
      cerebellar granule neurons (CGNs) in a neuron-type-dependent manner. In the
      present study, we investigated the mechanisms by which the growth of CGN axons
      was severely suppressed upon GSK3 inhibition. Using time-lapse imaging of
      cultured CGNs at early morphogenesis, we found that extension of the leading
      process was severely inhibited by the pharmacological inhibition of GSK3. The
      rate of somal migration was also reduced with a GSK3 inhibitor in dissociated
      culture as well as in microexplant culture. In addition, CGNs ectopically
      expressed with a catalytically inactive mutant of GSK3 exhibited a migration
      defect in vivo. In axonal leading processes of CGNs, detyrosination and
      acetylation of alpha-tubulin, which are known to correlate with microtubule
      stability, were decreased by GSK3 inhibition. A photoconversion analysis found
      that inhibition of GSK3 increases the turnover of microtubules. Furthermore, in
      the presence of paclitaxel, a microtubule-stabilizing reagent, inhibition of GSK3
      recovered the axonal leading process extension that was reduced by paclitaxel.
      Our results suggest that GSK3 supports the extension of axonal processes by
      stabilizing microtubules, contrary to its function in other neuron-types, lending
      mechanical insight into neuron-type-dependent morphological regulation.

PMID- 29653083
TI  - Aberrant RNA translation in fragile X syndrome: From FMRP mechanisms to emerging
      therapeutic strategies.
AB  - Research in the past decades has unfolded the multifaceted role of Fragile X
      mental retardation protein (FMRP) and how its absence contributes to the
      pathophysiology of Fragile X syndrome (FXS). Excess signaling through group 1
      metabotropic glutamate receptors is commonly observed in mouse models of FXS,
      which in part is attributed to dysregulated translation and downstream signaling.
      Considering the wide spectrum of cellular and physiologic functions that loss of
      FMRP can affect in general, it may be advantageous to pursue disease mechanism
      based treatments that directly target translational components or signaling
      factors that regulate protein synthesis. Various FMRP targets upstream and
      downstream of the translational machinery are therefore being investigated to
      further our understanding of the molecular mechanism of RNA and protein synthesis
      dysregulation in FXS as well as test their potential role as therapeutic
      interventions to alleviate FXS associated symptoms. In this review, we will
      broadly discuss recent advancements made towards understanding the role of FMRP
      in translation regulation, new pre-clinical animal models with FMRP targets
      located at different levels of the translational and signal transduction pathways
      for therapeutic intervention as well as future use of stem cells to model FXS
      associated phenotypes.

PMID- 29653084
TI  - Calcium dobesilate: A drug treatment for diabetic retinopathy can negatively
      interfere with the measurement of glycated albumin using the enzymatic method.
AB  - BACKGROUND: We reported that calcium dobesilate, a vasoprotective agent mainly
      used for diabetic retinopathy (DR), negatively interferes with glycated albumin
      (GA) assays involving enzymatic methods. METHODS: A calcium dobesilate standard
      was added to 3serum pools in vitro to prepare concentration-response series
      according to Clinical and Laboratory Standards Institute EP7-A2 guidelines.
      Percentage deviation between each drug concentration and the drug-free sample was
      calculated for 6 commercially available GA assays. The acceptable limit of
      deviation for GA was +/-5.61%. For in vivo analyses, changes in serum
      concentrations of GA and calcium dobesilate were monitored in eight healthy
      participants before and after oral calcium dobesilate administration. RESULTS: At
      16 MUg/ml calcium dobesilate, within the therapeutic range, the percentage
      deviations for Asahi Kasei, Maccura, Leadman, Homa, and Medicalsystem assays were
      -8.7% to -49.7%, -2.0% to -47.7%, and -10.1% to -35.7% for low-, medium- and high
      GA level interference pools, respectively, exhibiting dose-dependent negative
      interference. In vivo, calcium dobesilate ingestion was associated with
      statistically significant, falsely decreased measurements in 5 GA assays, 2 h
      after daily 500 mg administration. CONCLUSIONS: Calcium dobesilate ingestion was
      associated with erroneously low measurements in 5 GA assays. The degree of
      interference varied greatly among the assays examined.

PMID- 29653085
TI  - Prognostic significance of pre-resection albumin/fibrinogen ratio in patients
      with non-small cell lung cancer: A propensity score matching analysis.
AB  - BACKGROUND: Nutrition and coagulation play important roles in cancer progression.
      This study was aimed to investigate the value of the albumin/fibrinogen ratio
      (AFR) in non-small cell lung cancer (NSCLC) patients, through a propensity score
      matching (PSM) method. METHODS: We retrospectively analyzed 529 NSCLC patients
      underwent surgical resection from 2010 to 2015. PSM was used to eliminate
      possible biases. A Cox proportional hazards regression model was performed to
      evaluate the prognostic value of AFR in NSCLC. RESULTS: The optimal value was
      9.67 for the AFR by ROC (receiver operating characteristic) curve. The AFR was
      statistically significantly associated with age, sex, smoking history,
      histological subtype, tumor size, pathological stage and adjuvant therapy (p <
      0.05). Multivariate analysis indicated that the pathological stage and pre
      resection AFR were independent prognostic factors for patients with NSCLC.
      Additionally, elevated AFR indicated a better outcome, and patients with higher
      AFR had lower risk for overall death (OS) (HR 0.512, 95% CI 0.316-0.829, p =
      0.006) as well as disease-free death (DFS) (HR 0.561, 95% CI 0.399-0.787, p =
      0.001). The propensity score model identified 120 patients from each group that
      were balanced for age, sex, smoking history, histological subtype, tumor size,
      stage distribution and adjuvant therapy. In multivariable regression analysis of
      PSM groups, the result indicated that the AFR was predictive for OS (HR 0.392,
      95% CI 0.225-0.683, p < 0.001) and DFS (HR 0.526, 95% CI 0.344-0.805, p = 0.003).
      CONCLUSIONS: Pre-resection AFR can be considered as an independent prognostic
      factor in NSCLC patients, and higher AFR may enhance OS and DFS of NSCLC
      patients.

PMID- 29653086
TI  - A Surprising Diagnosis: Syphilitic Gastritis and Hepatitis.

PMID- 29653087
TI  - Purulent Pneumococcal Pericarditis: An Uncommon Presentation in the Vaccination
      Era.

PMID- 29653088
TI  - Nodal and BMP dispersal during early zebrafish development.
AB  - The secreted TGF-beta superfamily signals Nodal and BMP coordinate the patterning
      of vertebrate embryos. Nodal specifies endoderm and mesoderm during germ layer
      formation, and BMP specifies ventral fates and patterns the dorsal/ventral axis.
      Five major models have been proposed to explain how the correct distributions of
      Nodal and BMP are achieved within tissues to orchestrate embryogenesis:
      source/sink, transcriptional determination, relay, self-regulation, and
      shuttling. Here, we discuss recent experiments probing these signal dispersal
      models, focusing on early zebrafish development.

PMID- 29653089
TI  - Modification of levosimendan-induced suppression of atrial natriuretic peptide
      secretion in hypertrophied rat atria.
AB  - This study aimed to determine the effects of levosimendan, a calcium sensitizer,
      on atrial contractility and atrial natriuretic peptide (ANP) secretion and its
      modification in hypertrophied atria. Isolated perfused beating rat atria were
      used from control and isoproterenol-treated rats. Levosimendan and its metabolite
      OR-1896 caused a positive inotropic effect and suppressed ANP secretion in rat
      atria. Similar to levosimendan, the selective phosphodiesterase 3 (PDE3) or PDE4
      inhibitor also suppressed ANP secretion. Suppression of ANP secretion by 1 uM
      levosimendan was abolished by PDE3 inhibitor, but reversed by PDE4 inhibitor.
      Levosimendan-induced suppression of ANP secretion was potentiated by KATP channel
      blocker, but blocked by KATP channel opener. Levosimendan alone did not
      significantly change cyclic adenosine monophosphate (cAMP) efflux in the
      perfusate; however, levosimendan combined with PDE4 inhibitor markedly increased
      this efflux. The stimulation of ANP secretion induced by levosimendan combined
      with PDE4 inhibitor was blocked by the protein kinase A (PKA) inhibitor. In
      isoproterenol-treated atria, levosimendan augmented the positive inotropic effect
      and ANP secretion in response to an increased extracellular calcium concentration
      ([Ca+]o). These results suggests that levosimendan suppresses ANP secretion by
      both inhibiting PDE3 and opening KATP channels and that levosimendan combined
      with PDE4 inhibitor stimulates ANP secretion by activating the cAMP-PKA pathway.
      Modification of the effects of levosimendan on [Ca+]o-induced positive inotropic
      effects and ANP secretion in isoproterenol-treated rat atria might be related to
      a disturbance in calcium metabolism.

PMID- 29653091
TI  - A nation-wide genetic survey revealed a complex population structure of Bemisia
      tabaci in Pakistan.
AB  - The whitefly, Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) is a cryptic
      species complex distributed worldwide. In Pakistan, B. tabaci poses a serious
      threat to agriculture production. To understand its diversity in Pakistan, a
      large-scale sampling was conducted from various locations of all four provinces
      of the country and Mitochondrial cytochrome oxidase I (mtCOI) gene sequencing was
      used to determine the whiteflies genetically. The study revealed the presence of
      five different cryptic species in Pakistan namely Asia II-1, Asia II-5, Asia II
      7, Asia II-8 and MEAM-1, respectively. Among them, Asia II-1, which was
      previously reported from a few areas in the country, had been found now to be
      prevalent all over the country covering 88.7% of all the sequenced samples. Based
      on the mtCOI sequences and genetic distance analyses, the diversity of Asia II-1
      was much greater than all other cryptic species, which exist only in small
      patches.

PMID- 29653090
TI  - Vascular and molecular pharmacology of the metabolically stable CGRP analogue,
      SAX.
AB  - The main purpose of this study was to compare in vitro pharmacological properties
      of human alphaCGRP (CGRP) and a recently discovered metabolically stable CGRP
      analogue, SAX, in isolated rat and human artery segments. In rat, CGRP and SAX
      induced similar vasodilatory responses in isolated mesenteric artery with the
      potency of SAX being lower than that of CGRP (vasodilatory pEC50 8.2 +/- 0.12 and
      9.0 +/- 0.11, respectively). A corresponding difference in receptor binding
      affinity of SAX and CGRP was determined in rat cerebral membranes (pKi 8.3 +/-
      0.19 and 9.3 +/- 0.14, respectively). CGRP and SAX-induced vasodilation was
      antagonised with similar potencies by the CGRP receptor antagonist BIBN4096BS
      supporting a uniform receptor population for the agonists. In human tissue, SAX
      and CGRP induced similar pharmacological responses with different potencies in
      subcutaneous artery (vasodilatory pEC50 8.8 +/- 0.18 and 9.5 +/- 0.13,
      respectively) and human recombinant receptors (cAMP signalling pEC50 9.1 +/- 0.16
      and 10.2 +/- 0.19). Like in the rat mesenteric artery, both SAX and CGRP
      responses were inhibited by the CGRP receptor antagonist BIBN4096BS with similar
      antagonistic potencies. In conclusion, all pharmacological characteristics of SAX
      and CGRP in human and rat sources points towards action via a uniform BIBN4096BS
      sensitive receptor population with the potency of SAX being 5-10 fold lower than
      that of CGRP.

PMID- 29653092
TI  - CD10 inhibits cell motility but expression is associated with advanced stage
      disease in colorectal cancer.
AB  - INTRODUCTION: CD10 is a cell membrane-bound endopeptidase which is expressed in
      normal small bowel but not in normal colon. It is aberrantly expressed in a small
      proportion of colorectal cancers (CRC) and this has been associated with liver
      metastasis and poor prognosis. We sought to investigate the mechanism of CD10
      activity and its association with clinicopathological features. MATERIAL AND
      METHODS: CD10 was stably knocked down by lentiviral shRNA transduction in the CRC
      cell lines SW480 and SW620 which are derived from a primary tumour and its
      corresponding metastasis respectively. Expression of epithelial - mesenchymal
      transition (EMT) markers was tested as well as the effect of knockdown on cell
      viability, migration and invasion assays. In addition, immunohistochemical
      expression of CD10 in primary colorectal tumours (N = 84) in a tissue microarray
      was digitally quantified and analysed for associations with clinicopathological
      variables. RESULTS: Knockdown of CD10 did not alter cell viability in SW480, but
      migration and invasion levels increased (P < 0.001 for each) and this was
      associated with a cadherin switch. In SW620, CD10 knockdown caused a reduction in
      cell viability after 72 h (P = 0.0018) but it had no effect on cell migration and
      invasion. Expression of epithelial CD10 in primary tumours was associated with
      presence of lymph node invasion (P = 0.001) and advanced Duke's stage (P =
      0.001). CONCLUSIONS: Our results suggest that the function of CD10 may change
      during tumour evolution. It may inhibit cell motility in early-stage disease
      whilst promoting cell viability in late-stage disease. It has a complex role and
      further studies are needed to elucidate the suitability of CD10 as a prognostic
      marker or therapeutic target.

PMID- 29653094
TI  - Biotypes: The Tip of the Research Domain Criteria Iceberg.

PMID- 29653095
TI  - Examining Functional Resting-State Connectivity in Psychosis and Its Subgroups in
      the Bipolar-Schizophrenia Network on Intermediate Phenotypes Cohort.
AB  - BACKGROUND: We sought to examine resting-state functional magnetic resonance
      imaging connectivity measures in psychotic patients to both identify cumulative
      differences across psychosis and subsequently probe deficits across conventional
      DSM-IV diagnoses and a newly identified classification using
      cognitive/neurophysiological data (Biotypes). METHODS: We assessed 1125 subjects,
      including healthy control subjects, probands (schizophrenia, schizoaffective
      disorder, psychotic bipolar disorder), and relatives of probands. Probands and
      relatives were also segregated into Biotype groups (B1-B3, B1R-B3R using a method
      reported previously). Empirical resting-state functional magnetic resonance
      imaging networks were derived using independent component analysis. Global
      psychosis-related abnormalities were first identified. Subsequent post hoc t
      tests were performed across various diagnostic categories. Follow-up linear mixed
      model compared significance of within-proband differences across categories.
      Secondary analyses assessed correlations with biological profile scores. RESULTS:
      Voxelwise tests between proband and control subjects revealed nine abnormal
      networks. Post hoc analysis revealed lower connectivity in most networks for all
      proband subgroups (DSM and Biotypes). Within-proband effect sizes of
      discrimination were marginally better for Biotypes over DSM. Reduced connectivity
      was noted in relatives of patients with schizophrenia in two networks and
      relatives of patients with psychotic bipolar disorder in one network. Biotype
      relatives showed similar deficits in one network. Connectivity deficits across
      four networks were significantly associated with cognitive control profile
      scores. CONCLUSIONS: Overall, we found psychosis-related connectivity deficits in
      nine large-scale networks. Deficits in these networks tracked more closely with
      cognitive control factors, suggesting potential implications for disease
      profiling and therapeutic intervention. Biotypes performed marginally better in
      terms of separating out psychosis subgroups compared with conventional DSM or
      psychiatric diagnoses.

PMID- 29653096
TI  - Effects of Psychotherapy on Neuronal Correlates of Reappraisal in Female Patients
      With Borderline Personality Disorder.
AB  - BACKGROUND: Emotion dysregulation is a fundamental aspect of borderline
      personality disorder (BPD). Accordingly, one major focus of dialectical behavior
      therapy (DBT) is to teach strategies to regulate emotional reactions. To date,
      little is known about the neural mechanisms linked to the amelioration of BPD
      symptoms after therapy. In the present study, we used functional magnetic
      resonance imaging to investigate neural correlates of explicit emotion regulation
      before and after DBT. METHODS: Female BPD patients (n = 32) performed a
      reappraisal task before and after a 12-week inpatient DBT program and were
      compared with 24 healthy control participants. Based on the change in symptom
      severity, the BPD group was separated into responders and nonresponders and
      compared with a clinical control group of 16 BPD patients. Both control groups
      were scanned twice within 12 weeks. RESULTS: After DBT, BPD patients showed
      decreased insula and anterior cingulate cortex activity during reappraisal.
      Anterior cingulate connectivity to medial and superior frontal gyrus, superior
      temporal gyrus, and inferior parietal cortices increased after DBT. Responders
      exhibited reduced activation in amygdala, anterior cingulate cortex,
      orbitofrontal, and dorsolateral prefrontal cortex together with increased
      connectivity within a limbic-prefrontal network during the reappraisal of
      negative stimuli after psychotherapy. CONCLUSIONS: This study revealed reduced
      activity and increased connectivity in neural networks related to salience
      processing and emotion regulation after therapy. Attenuated limbic hyperarousal
      together with an elevated coupling between limbic and prefrontal and inferior
      parietal control regions in BPD patients after successful therapy may indicate
      more efficient emotion regulation during reappraisal of negative pictures.

PMID- 29653097
TI  - ?

PMID- 29653098
TI  - Reaction kinetic studies for comparison of mutagenic potency between butadiene
      monoxide and glycidamide.
AB  - DNA adducts can be formed from covalent binding of electrophilic reactive
      compounds to the nucleophilic N- and O-atoms of the biomolecule. The O-sites on
      DNA, with nucleophilic strength (n) of ca. 2, is recognized as a critical site
      for mutagenicity. Characterization of the reactivity of electrophilic compounds
      at the O-sites can be used to predict their mutagenic potency in relative terms.
      In the present study, reaction kinetic experiments were performed for butadiene
      monoxide (BM) in accordance with the Swain-Scott relation using model
      nucleophiles representing N- and O-sites on DNA, and earlier for glycidamide (GA)
      using a similar approach. The epoxide from the kinetic experiments was trapped by
      cob(I)alamin, resulting in formation of an alkylcobalamin which was analyzed by
      liquid chromatography tandem mass spectrometry. The Swain-Scott relationship was
      used to determine selectivity constant (s) of BM and GA as 0.86 and 1.0,
      respectively. The rate constant for the reaction at n of 2 was extrapolated to
      0.023 and 0.038 M-1 h-1 for BM and GA, respectively, implying a higher mutagenic
      potency per dose unit of GA compared to BM. The reaction kinetic parameters
      associated with mutagenic potency were also estimated by a density functional
      theory approach, which were in accordance to the experimental determined values.
      These types of reaction kinetic measures could be useful in development of a
      chemical reactivity based prediction tool that could aid in reduction of animal
      experiments in cancer risk assessment procedures for relative mutagenicity.

PMID- 29653099
TI  - Herbacetin, a flaxseed flavonoid, ameliorates high percent dietary fat induced
      insulin resistance and lipid accumulation through the regulation of hepatic lipid
      metabolizing and lipid-regulating enzymes.
AB  - Healthy plants and their constituents have been considered as a safe remedy for
      the treatment of obesity and obesity associated diseases. Herbacetin is a dietary
      flavonoid that has been explored for many pharmacological activities; but, the
      anti-hyperglycaemic and anti-hyperlipidemic properties of herbacetin have not yet
      been explored. The present study was performed to evaluate the ameliorative
      effect of herbacetin on high-fat diet-induced hyperglycaemia and hyperlipidemia
      in 57BL/6 J mice. Obesity associated insulin resistance was induced by
      continuously feeding the mice with high-fat diet for 10 weeks. Afterwards, mice
      were subjected to intragastric administration of herbacetin (different doses)
      daily along with high-fat diet for the next 5 weeks. At the end of 106th day,
      changes in body weight, blood glucose, insulin, HOMA-IR, and lipids profiles and
      lipid-regulating enzymes were evaluated. Herbacetin significantly reduced the
      body weight, plasma glucose, plasma insulin, and HOMA-IR activity in obesity
      associated insulin resistant mice (OIR). In addition, herbacetin administration
      significantly reduced the plasma and hepatic total cholesterol, triglycerides,
      and free fatty acids in OIR mice. Moreover, herbacetin significantly improved the
      altered hepatic lipid metabolizing and lipid-regulating enzymes such as SREBP-1c,
      and 2, fatty acid synthase (FAS), fatty acid beta-oxidation (beta-oxidation),
      malic enzyme, glucose 6-phosphate dehydrogenase (G6PD), and carnitine
      palmitoyltransferase (CPT) when compared to OIR control mice. Histopathological
      examination clearly showed that herbacetin decreases lipid droplets in the liver
      tissue. Thus, observed results strongly indicate that herbacetin provides
      remarkable protection against the harmful effects of chronic high-fat diet
      consumption because of its anti-hyperglycaemic and anti-hyperlipidemic properties
      through the regulation of hepatic lipid metabolizing and lipid-regulating
      enzymes.

PMID- 29653100
TI  - Vitamin D nanoemulsion enhances hepatoprotective effect of conventional vitamin D
      in rats fed with a high-fat diet.
AB  - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is associated with
      hyperlipidemia, obesity and type II diabetes. Due to increasing prevalence of
      these diseases globally, NAFLD is considered as a common form of chronic liver
      diseases. Vitamin D is a fat soluble vitamin with reported anti-inflammatory,
      anti-oxidant and immune modulating activity. Hypovitaminosis D often coexists
      with NAFLD and various studies reported beneficial role of vitamin D in
      modulating NAFLD. However, variable oral bioavailability, poor water solubility,
      and chemical degradation hinder the clinical application of vitamin D. PURPOSE:
      We evaluated the potential protective effect of Vitamin D nanoemulsion (developed
      by sonication and pH-Shifting of pea protein isolate and canola oil) compared to
      conventional vitamin D against liver injury in rats fed with high fat diet (HFD).
      METHODS: We analyzed liver function enzymes, lipid profile, lipid metabolism,
      levels and histopathology of inflammation and fibrosis in rat liver tissues.
      RESULTS: HFD fed rats exhibited deterioration of liver function, poor lipid
      profile, decreased fatty acid oxidation and up-regulation of inflammatory
      cytokines and extracellular matrix deposition. Vitamin D administration reduced
      elevated liver enzymes, improved lipid profile, enhanced fatty acid oxidation and
      attenuated liver inflammation and fibrosis. Interestingly, vitamin D nanoemulsion
      was superior to conventional vitamin D with remarkable hepatoprotective effect
      against HFD-induced liver injury. CONCLUSION: This study demonstrated vitamin D
      nanoemulsion as a more efficient formulation with more prominent hepatoprotective
      effect against HFD-induced liver injury compared to conventional oral vitamin D.

PMID- 29653101
TI  - beta1-integrin is a cell-autonomous factor mediating the Numb pathway for cardiac
      progenitor maintenance.
AB  - Proper control of multipotent/stem cell number and fate is essential for ensuing
      organ formation during development. beta1-integrin, a subfamily of cell surface
      receptors, has a conserved role in maintenance of multipotent/stem cells,
      including renal progenitor cells, follicle stem cells, epidermal stem cells and
      neural stem cells. However, it remains unclear whether beta1-integrin has a role
      in cardiac progenitor cell (CPC) development. Here we show that a mesodermal
      deletion of beta1-integrin decreases Isl1+ cell number in the second pharyngeal
      arch (PA2), where CPCs undergo renewal and expansion. Mesp1 lineage-specific
      mosaicism revealed that beta1-integrin-deleted Isl1+ cells do not proliferate in
      the PA2. Consistently, beta1-integrin-deleted Isl1+ CPCs failed to expand in
      vitro, independent of PA2 cells. beta1-integrin co-localized and physically
      associated with Numb, a crucial regulator of CPC renewal and expansion.
      Importantly, Numb/Numbl-deleted CPCs showed dramatic reduction in beta1-integrin
      levels. These findings suggest that beta1-integrin is a key mediator of the Numb
      pathway in CPC maintenance.

PMID- 29653102
TI  - Visceral adipose tissue-derived serine protease inhibitor accelerates cholesterol
      efflux by up-regulating ABCA1 expression via the NF-kappaB/miR-33a pathway in THP
      1 macropahge-derived foam cells.
AB  - Atherosclerosis is a dyslipidemia disease characterized by foam cell formation
      driven by the accumulation of lipids. Visceral adipose tissue-derived serine
      protease inhibitor (vaspin) is known to suppress the development of
      atherosclerosis via its anti-inflammatory properties, but it is not yet known
      whether vaspin affects cholesterol efflux in THP-1 macrophage-derived foam cells.
      Here, we investigated the effects of vaspin on ABCA1 expression and cholesterol
      efflux, and further explored the underlying mechanism. We found that vaspin
      decreased miR-33a levels, which in turn increased ABCA1 expression and
      cholesteorl efflux. We also found that inhibition of NF-kappaB reduced miR-33a
      expression and vaspin suppressed LPS-mediated NF-kappaB phosphorylation. Our
      findings suggest that vaspin is not only a regular of inflammasion but also a
      promoter of cholesterol efflux.

PMID- 29653103
TI  - Sterol regulatory element binding protein 1 trans-activates 25-hydroxy vitamin D3
      24-hydroxylase gene expression in renal proximal tubular cells.
AB  - The physiological activity of the steroid derived hormone vitamin D is regulated
      by several enzymatic steps. Both 25-hydroxy vitamin D3 1alpha-hydroxylase
      (CYP27B1) and 25-hydroxyvitamin D3 24-hydroxylase (CYP24A1) modulate blood levels
      of 1,25-dihydroxyvitamin D3, an activated form of vitamin D. We previously
      demonstrated that CYP27B1 expression was trans-activated by sterol regulatory
      element binding protein 1 (SREBP1), although whether SREBP1 also regulates
      CYP24A1 transcription was unclear. Here we investigated the ability of SREBP1 to
      affect CYP24A1 transcription. In a luciferase reporter assay, mouse and human
      CYP24A1 promoter activity was strongly activated by SREBP1 in opossum kidney
      proximal tubular cells (OK-P). Three putative SREs (pSREs) were found in the
      mouse Cyp24a1 gene promoter and the SREBP1 protein showed specific binding to the
      pSRE1 element in EMSAs. Site-directed mutagenesis of the pSRE1 element strongly
      decreased SREBP1-mediated Cyp24a1 gene transcription. Moreover, siRNA-mediated
      SREBP1 knock-down repressed CYP24A1 expression in human renal proximal tubular
      epithelial cells (HKC-8). In animal studies, mice given various doses of thyroid
      hormone (T3) showed dose-dependent reductions in renal Srebp1c and Cyp24a1 mRNA
      levels. Taken together, our results suggest that SREBP1 trans-activates CYP24A1
      expression through SREBP binding elements present in the promoter.

PMID- 29653104
TI  - The malaria parasite RhopH protein complex interacts with erythrocyte calmyrin
      identified from a comprehensive erythrocyte protein library.
AB  - Malaria merozoite apical organelles; microneme and rhoptry secreted proteins play
      functional roles during and following invasion of host erythrocytes. Among
      numerous proteins, the rhoptries discharge high molecular weight proteins known
      as RhopH complex. Recent reports suggest that the RhopH complex is essential for
      growth and survival of the malaria parasite within erythrocytes. However, an in
      depth understanding of the host-parasite molecular interactions is indispensable.
      Here we utilized a comprehensive mouse erythrocyte protein library consisting of
      443 proteins produced by a wheat germ cell-free system, combined with AlphaScreen
      technology to identify mouse erythrocyte calmyrin as an interacting molecule of
      the rodent malaria parasite Plasmodium yoelii RhopH complex (PyRhopH). The
      PyRhopH interaction was dependent on the calmyrin N-terminus and divalent cation
      capacity. The finding unveils a recommendable and invaluable usefulness of our
      comprehensive mouse erythrocyte protein library together with the AlphaScreen
      technology in investigating a wide-range of host-parasite molecular interactions.

PMID- 29653105
TI  - CST3 and GDF15 ameliorate renal fibrosis by inhibiting fibroblast growth and
      activation.
AB  - The final strategies to care patients with end-stage renal fibrosis rely on
      dialysis and kidney transplantation. Because such treatments are invasive and
      cause health problems eventually, it is necessary to develop new therapeutic
      strategies for delaying the disease progress. We here searched for cytokines
      showing an anti-fibrotic activity in cell-based experiments. Cystatin C (CST3)
      and Growth differentiation factor 15 (GDF15) were identified to have anti
      fibrotic activities in a cytokine array screening. In primary fibroblasts
      isolated from the mouse kidneys subjected to ureteral obstruction-induced
      fibrosis, each cytokine induced apoptotic cell death and reduced collagen
      production. These anti-fibrotic effects were further augmented by co
      administration of both cytokines. Mechanistically, CST3 and GDF15 were found to
      block the TGF-beta receptor and the N-Myc signaling pathways, respectively. In
      mice with unilateral ureter obstruction, each cytokine and the combination of two
      cytokines effectively reduced the fibrotic burden in the subjected kidneys.
      Therefore, we propose that CST3 and GDF15 could be potential candidates for
      biopharmaceutics to ameliorate renal fibrosis.

PMID- 29653106
TI  - Assessment of Nociception and Pain in Participants in an Unresponsive or
      Minimally Conscious State After Acquired Brain Injury: The Relation Between the
      Coma Recovery Scale-Revised and the Nociception Coma Scale-Revised.
AB  - OBJECTIVES: To investigate the relation between consciousness and nociceptive
      responsiveness (ie, Nociception Coma Scale-Revised [NCS-R]), to examine the
      suitability of the NCS-R for assessing nociception in participants with disorders
      of consciousness (DOC), and to replicate previous findings on psychometric
      properties of the scale. DESIGN: Specialized DOC program. SETTING: Specialized
      DOC program and university hospitals. PARTICIPANTS: Participants (N=85) diagnosed
      with DOC. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: We prospectively
      assessed consciousness with the Coma Recovery Scale-Revised (CRS-R). Responses
      during baseline, non-noxious, and noxious stimulations were scored with the NCS-R
      and CRS-R oromotor and motor subscales. RESULTS: CRS-R total scores correlated
      with NCS-R total scores and subscores. CRS-R motor subscores correlated with NCS
      R total scores and motor subscores, and CRS-R oromotor subscores correlated with
      NCS-R total scores as well as verbal and facial expression subscores. There was a
      difference between unresponsive wakefulness syndrome and minimally conscious
      state in the proportion of grimacing and/or crying participants during noxious
      conditions. We replicated previous findings on psychometric properties of the
      scale but found a different score as the best threshold for nociception.
      CONCLUSIONS: We report a strong relation between the responsiveness to
      nociception and the level of consciousness. The NCS-R seems to be a valuable tool
      for assessing nociception in an efficient manner, but additional studies are
      needed to allow recommendations for clinical assessment of subjective pain
      experience.

PMID- 29653107
TI  - Interrater and Intrarater Reliability of the Balance Computerized Adaptive Test
      in Patients With Stroke.
AB  - OBJECTIVE: To examine the interrater and intrarater reliability of the Balance
      Computerized Adaptive Test (Balance CAT) in patients with chronic stroke having a
      wide range of balance functions. DESIGN: Repeated assessments design (1wk apart).
      SETTING: Seven teaching hospitals. PARTICIPANTS: A pooled sample (N=102)
      including 2 independent groups of outpatients (n=50 for the interrater
      reliability study; n=52 for the intrarater reliability study) with chronic
      stroke. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Balance CAT.
      RESULTS: For the interrater reliability study, the values of intraclass
      correlation coefficient, minimal detectable change (MDC), and percentage of MDC
      (MDC%) for the Balance CAT were .84, 1.90, and 31.0%, respectively. For the
      intrarater reliability study, the values of intraclass correlation coefficient,
      MDC, and MDC% ranged from .89 to .91, from 1.14 to 1.26, and from 17.1% to 18.6%,
      respectively. CONCLUSIONS: The Balance CAT showed sufficient intrarater
      reliability in patients with chronic stroke having balance functions ranging from
      sitting with support to independent walking. Although the Balance CAT may have
      good interrater reliability, we found substantial random measurement error
      between different raters. Accordingly, if the Balance CAT is used as an outcome
      measure in clinical or research settings, same raters are suggested over
      different time points to ensure reliable assessments.

PMID- 29653108
TI  - Validation of the Narrowing Beam Walking Test in Lower Limb Prosthesis Users.
AB  - OBJECTIVE: To evaluate the content, construct, and discriminant validity of the
      Narrowing Beam Walking Test (NBWT), a performance-based balance test for lower
      limb prosthesis users. DESIGN: Cross-sectional study. SETTING: Research
      laboratory and prosthetics clinic. PARTICIPANTS: Unilateral transtibial and
      transfemoral prosthesis users (N=40). INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURES: Content validity was examined by quantifying the percentage of
      participants receiving maximum or minimum scores (ie, ceiling and floor effects).
      Convergent construct validity was examined using correlations between
      participants' NBWT scores and scores or times on existing clinical balance tests
      regularly administered to lower limb prosthesis users. Known-groups construct
      validity was examined by comparing NBWT scores between groups of participants
      with different fall histories, amputation levels, amputation etiologies, and
      functional levels. Discriminant validity was evaluated by analyzing the area
      under each test's receiver operating characteristic (ROC) curve. RESULTS: No
      minimum or maximum scores were recorded on the NBWT. NBWT scores demonstrated
      strong correlations (rho=.70-.85) with scores/times on performance-based balance
      tests (timed Up and Go test, Four Square Step Test, and Berg Balance Scale) and a
      moderate correlation (rho=.49) with the self-report Activities-specific Balance
      Confidence scale. NBWT performance was significantly lower among participants
      with a history of falls (P=.003), transfemoral amputation (P=.011), and a lower
      mobility level (P<.001). The NBWT also had the largest area under the ROC curve
      (.81) and was the only test to exhibit an area that was statistically
      significantly >.50 (ie, chance). CONCLUSIONS: The results provide strong evidence
      of content, construct, and discriminant validity for the NBWT as a performance
      based test of balance ability. The evidence supports its use to assess balance
      impairments and fall risk in unilateral transtibial and transfemoral prosthesis
      users.

PMID- 29653109
TI  - Can Older Adults Accurately Report Their Use of Physical Rehabilitation Services?
AB  - OBJECTIVE: To explore the accuracy of rehabilitation service use reports by older
      adults as well as variation in accuracy by demographic characteristics, time
      since use, duration, and setting (inpatient, outpatient, home). DESIGN:
      Longitudinal observational study. SETTING: Participants' homes. PARTICIPANTS:
      Community-dwelling adults ages 65 and older (N=4228) in the 2015 National Health
      and Aging Trends Study who were enrolled in Medicare Parts A and B for 12 months
      before their interview. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      Respondents were asked whether they received rehabilitation services in the past
      year and the duration and location of services. Healthcare Common Procedure
      Coding System codes and Revenue Center codes were used to identify Medicare
      eligible rehabilitation service. RESULTS: Survey-based reports and Medicare
      claims yielded similar estimates of rehabilitation use over the past year. Self
      reported measures had high sensitivity (77%) and positive predictive value (80%)
      and even higher specificity and negative predictive value (approaching 95%).
      However, in adjusted models, sensitivity was lower for black enrollees, the very
      old, and those with lower education levels. CONCLUSIONS: Survey-based measures of
      rehabilitation accurately captured use over the past year, but differential
      reporting should be considered when characterizing rehabilitation use in certain
      subgroups of older Americans.

PMID- 29653110
TI  - siRNA - Mediated LRP/LR knock-down reduces cellular viability of malignant
      melanoma cells through the activation of apoptotic caspases.
AB  - : The 37 kDa/67 kDa laminin receptor (LRP/LR) is over-expressed in tumor cells
      and has been implicated in several tumourigenic processes such as metastasis and
      telomerase activation, however, more importantly the focus of the present study
      is on the maintenance of cellular viability and the evasion of apoptosis. The aim
      of the study was to investigate the role of LRP/LR on the cellular viability of
      early (A375) and late stage (A375SM) malignant melanoma cells. Flow cytometry and
      western blot analysis revealed that A375SM cells contain more cell-surface and
      total LRP/LR levels in comparison to the A375 cells, respectively. In order to
      determine the effect of LRP/LR on cell viability and apoptosis, LRP was down
      regulated via siRNA technology. MTT assays revealed that LRP knock-down led to
      significant reductions in the viability of A375 and A375SM cells. Confocal
      microscopy indicated nuclear morphological changes suggestive of apoptotic
      induction in both cell lines and Annexin-V FITC/PI assays confirmed this
      observation. Additionally, caspase-3 activity assays revealed that apoptosis was
      induced in both cell lines after siRNA-mediated down-regulation of LRP. Caspase-8
      and -9 activity assays suggested that post LRP knock-down; A375 cells undergo
      apoptosis solely via the extrinsic pathway, while A375SM cells undergo apoptosis
      via the intrinsic pathway. IMPLICATIONS: siRNAs mediated LRP knock-down might
      represent a powerful alternative therapeutic strategy for the treatment of
      malignant melanoma through the induction of apoptosis.

PMID- 29653111
TI  - A brain within the heart: A review on the intracardiac nervous system.
AB  - Cardiac function is under the control of the autonomic nervous system, composed
      by the parasympathetic and sympathetic divisions, which are finely tuned at
      different hierarchical levels. While a complex regulation occurs in the central
      nervous system involving the insular cortex, the amygdala and the hypothalamus, a
      local cardiac regulation also takes place within the heart, driven by an
      intracardiac nervous system. This complex system consists of a network of
      ganglionic plexuses and interconnecting ganglions and axons. Each ganglionic
      plexus contains numerous intracardiac ganglia that operate as local integration
      centres, modulating the intricate autonomic interactions between the extrinsic
      and intracardiac nervous systems. Herein, we summarize the current understanding
      on the intracardiac nervous system, and acknowledge its role in the
      pathophysiology of cardiovascular diseases.

PMID- 29653112
TI  - A comparison of two types of running wheel in terms of mouse preference, health,
      and welfare.
AB  - Voluntary wheel running occurs in mice of all strains, sexes, and ages. Mice find
      voluntary wheel running rewarding, and it leads to numerous health benefits. For
      this reason wheels are used both to enhance welfare and to create models of
      exercise. However, many designs of running wheel are used. This makes between
      study comparisons difficult, as this variability could potentially affect the
      amount, pattern, and/or intensity of running behaviour, and thence the wheels'
      effects on welfare and exercise-related changes in anatomy and physiology. This
      study therefore evaluated two commercially available models, chosen because safe
      for group-housed mice: Bio Serv(r)'s "fast-trac" wheel combo and Ware
      Manufacturing Inc.'s stainless steel mesh 5" upright wheel. Working with a total
      of three hundred and fifty one female C57BL/6, DBA/2 and BALB/c mice, we assessed
      these wheels' relative utilization by mice when access was free; the strength of
      motivation for each wheel-type when access required crossing an electrified grid;
      and the impact each wheel had on mouse well-being (inferred from acoustic startle
      responses and neophobia) and exercise-related anatomical changes (BMI; heart and
      hind limb masses). Mice ran more on the "fast-trac" wheel regardless of whether
      both wheel-types were available at once, or only if one was present. In terms of
      motivation, subjects required to work to access a single wheel worked equally
      hard for both wheel-types (even if locked and thus not useable for running), but
      if provided with one working wheel for free and the other type of wheel (again
      unlocked) accessible via crossing the electrified grid, the "fast-trac" wheel
      emerged as more motivating, as the Maximum Price Paid for the Ware metal wheel
      was lower than that paid for the "fast-trac" plastic wheel, at least for C57BL/6s
      and DBA/2s. No deleterious consequences were noted with either wheel in terms of
      health and welfare, but only mice with plastic wheels developed significantly
      larger hearts and hind limbs than control animals with locked wheels. Thus, where
      differences emerged, Bio Serv(r)'s "fast-trac" wheel combos appeared to better
      meet the aims of exercise provision than Ware Manufacturing's steel upright
      wheels.

PMID- 29653113
TI  - Oral sensations and secretions.
AB  - Sensations experienced in the mouth influence food choices, both immediately and
      in the long term. Such sensations are themselves influenced by experience with
      flavors, the chemical environment of the mouth, genetics of receptors for
      flavors, and individual behavior in the chewing of food. Gustation, the sense of
      taste, yields information about nutrients, influences palatability, and feeds
      into the human body's preparation to receive those nutrients. Olfaction, the
      sense of smell, contributes enormously to defining and identifying food flavors
      (and is experienced even after placing food inside the mouth). Another vital
      component of food flavor is texture, which contributes to palatability,
      especially if a food's texture violates a person's expectations. Next,
      chemesthesis is the sense of chemically induced irritancy and temperature, for
      example spiciness and stinging. All of these sensations are potentially modified
      by saliva, the chemical and physical media of the mouth. As a person experiences
      the culmination of these oral sensations, modified through an individual's own
      unique saliva, the flavors in turn influence both what and how a person eats.

PMID- 29653114
TI  - Adrenal androgen measurement for assessing the selectivity of adrenal venous
      sampling in primary aldosteronism.
AB  - Adrenal venous sampling (AVS) is the reference standard for primary aldosteronism
      (PA) subtyping. Cortisol is widely used to assess the success of selective AVS,
      but it is not always reliable. The aim of the present study was to investigate
      the usefulness of adrenal androgens, compared to cortisol, in assessing the
      selectivity of AVS. We consecutively recruited 37 patients with PA undergoing
      AVS. AVS procedures were performed with the bilateral simultaneous technique
      without cosyntropin stimulation. We collected two baseline blood samples from 10
      patients with a 15-min interval between time-15 (t-15) and time 0 (t0) to measure
      the variability in the levels of the tested hormones over time. Cortisol,
      androstenedione, dehydroepiandrosterone (DHEA), and DHEA sulfate (DHEAS)
      concentrations were measured in adrenal and peripheral venous (AV and PV,
      respectively) samples. The selectivity index (SI) values for androstenedione and
      DHEA were on average 3.0- and 2.0-fold higher, respectively, than those for
      cortisol, respectively (P < 0.05). However, the SI for DHEAS was 5.0-fold lower
      than the SI for cortisol (P < 0.05). Plasma androstenedione and DHEA
      concentrations positively correlated with cortisol and aldosterone concentrations
      in AV samples (P < 0.01). Compared to cortisol, the variation ratio of AV
      androstenedione and DHEA decreased from t-15 to t0 (0.23 and 0.43 vs. 0.52; P =
      0.001 and P = 0.061, respectively). Using receiver operating characteristic
      curves, an SI >= 3 for androstenedione or DHEA provided optimal sensitivity and
      specificity in AVS. Given the much larger AV/PV ratios and reduced variability
      compared to cortisol, the adrenal androgens androstenedione and DHEA are useful
      for assessing the selectivity of AVS without cosyntropin stimulation and may be
      superior analytes in conditions with marked variability of cortisol levels or
      with adrenocortical tumors cosecreting cortisol and aldosterone.

PMID- 29653115
TI  - Facile one-pot multicomponent synthesis and molecular docking studies of
      steroidal oxazole/thiazole derivatives with effective antimicrobial, antibiofilm
      and hemolytic properties.
AB  - A series of steroidal oxazole and thiazole derivatives have been synthesized
      employing thiosemicarbazide/semicarbazide hydrochloride and ethyl 2
      chloroacetoacetate with a simple and facile one-pot multicomponent reaction
      pathway. The antimicrobial activity of newly synthesized compounds were evaluated
      against four bacterial strains namely Gram-negative (Escherichia coliand
      Pseudomonas aeruginosa) and Gram-positive bacteria (Staphylococcus aureus and
      Listeria monocytogenes) in addition to pathogenic fungi (Candida albicans and
      Cryptococcus neoformans). Bioactivity assay manifested that most of the compounds
      exhibited good antimicrobial activity. To provide additional insight into
      antimicrobial activity, the compounds were also tested for their antibiofilm
      activity against S. aureus biofilm. Moreover, molecular docking study shows
      binding of compounds with amino acid residues of DNA gyrase and glucosamine-6
      phosphate synthase (promising antimicrobial target) through hydrogen bonding
      interactions. Hemolytic activity have been also investigated to ascertain the
      effect of compounds over RBC lysis and results indicate good prospects for
      biocompatibility. The expedient synthesis of steroidal heterocycles, effective
      antibacterial and antifungal behavior against various clinically relevant human
      pathogens, promising biocompatibility offer opportunities for further
      modification and potential applications as therapeutic agents.

PMID- 29653116
TI  - Serum from Asian patients with atopic dermatitis is characterized by TH2/TH22
      activation, which is highly correlated with nonlesional skin measures.

PMID- 29653117
TI  - Potential role of extracellular vesicle-mediated antigen presentation in
      Helicobacter pylori hypersensitivity during eradication therapy.

PMID- 29653118
TI  - Acute high-intensity interval exercise induces comparable levels of circulating
      cell-free DNA and Interleukin-6 in obese and normal-weight individuals.
AB  - AIMS: Obesity is associated with lipid aggregation in adipocytes and macrophage
      infiltration, leading to increased oxidative stress and inflammation. Increased
      cell-free DNA (cfDNA) concentrations have been observed in clinical conditions of
      systemic inflammation. While the beneficial effects of regular physical activity
      on the release of circulating cfDNA still remain unknown, acute intense exercise
      has been shown to increase inflammatory cytokines and cfDNA concentrations in
      normal-weight individuals. Therefore, the primary purpose of this study was to
      examine the effect of acute high-intensity interval Exercise (HIIE) on plasma
      cfDNA and interleukin-6 (IL-6) responses in obese and normal-weight subjects.
      MAIN METHODS: Fourteen male subjects (7 obese and 7 normal-weight) participated
      in an acute HIIE protocol (30 min, 4x4min @ 80% - 90% of VO2max) on a treadmill.
      Between HIIE intervals, subjects performed 3 min of active recovery at 50-60%
      VO2max. Blood samples were collected prior to, immediately following exercise,
      and one hour into recovery for measurements of plasma cfDNA and IL-6. KEY
      FINDINGS: Our results demonstrated a significant elevation in plasma cfDNA
      immediately following acute HIIE in both obese and normal-weight subjects. A
      comparable elevation in the concentration of plasma IL-6 was also found between
      two groups in response to acute HIIE. Furthermore, the level of plasma cfDNA was
      not correlated with IL-6 either at baseline or in response to acute HIIE.
      SIGNIFICANCE: These findings may support the utilization of HIIE as a time
      efficient exercise protocol to understand the obesity-associated cfDNA and
      inflammatory responses.

PMID- 29653119
TI  - Adenovirus-mediated overexpression of sST2 attenuates cardiac injury in the rat
      with severe acute pancreatitis.
AB  - AIMS: Severe acute pancreatitis (SAP) is a serious disease associated with
      systematic inflammation and multiple organs dysfunction. Soluble ST2 (sST2), a
      member of the Toll interleukin (IL)-1 receptor (TIR) superfamily, has been
      demonstrated to exert immune-regulatory and anti-inflammatory properties in
      several inflammation-related diseases. In this study, we investigated whether
      transfer of sST2 gene by adenovirus vector could attenuate sodium taurocholate
      induced SAP and associated cardiac injury. MAIN METHODS: A rat model of SAP was
      induced by retrograde injection of 5% sodium taurocholate (1 ml/kg) into the
      biliopancreatic duct. Rats in the treatment groups were intravenously injected
      with adenovirus expressing sST2 (Ad-sST2, 1 * 109 particles/rat) or green
      fluorescent protein (Ad-GFP) via the tail vein 48 h before SAP induction.
      Histological changes in the pancreatic and heart tissues, and parameters for
      evaluating SAP and associated cardiac injury were determined at 24 h after SAP.
      KEY FINDINGS: Sodium taurocholate induced obvious pathological changes in
      pancreas and elevated serum levels of amylase and lipase. Furthermore, SAP
      animals exhibited significant cardiac impairment, evidenced by decreased cardiac
      function, increased myocardial apoptosis and cardiac-related enzymes including
      creatine kinase isoenzyme, lactate dehydrogenase, and Troponin T. Administration
      of Ad-sST2 markedly improved the structure of pancreas and heart tissues, and
      reversed the alterations in serum amylase, lipase and cardiac-related enzymes. In
      addition, Ad-sST2 treatment downregulated pro-inflammatory cytokines production,
      demonstrating the anti-inflammatory property of sST2. SIGNIFICANCE: Our results
      suggest that administration of Ad-sST2 significantly attenuated the severity of
      SAP and associated cardiac damage, and the cardioprotective effect is associated
      with its anti-inflammatory action.

PMID- 29653120
TI  - Covered versus uncovered self-expandable metal stent for palliation of primary
      malignant extrahepatic biliary strictures: a randomized multicenter study.
AB  - BACKGROUND AND AIMS: Self-expandable metal stents (SEMSs) are used to relieve
      malignant biliary obstructions. We aimed to compare stent patency, the adverse
      events rate, and overall survival of covered versus uncovered self-conformable
      metal stents in patients with primary malignant extrahepatic biliary strictures,
      not eligible for surgery. METHODS: This is a multicenter randomized trial
      analyzing 158 patients with inoperable distal malignant biliary obstruction
      conducted in 5 Italian referral centers between December 2014 and October 2016.
      Seventy-eight patients were randomized to receive a fully covered SEMS (FCSEMS),
      and 80 patients received uncovered SEMSs (USEMSs). Data from 148 (72 FCSEMSs and
      76 USEMSs) of 158 patients were analyzed. RESULTS: Median time of stent patency
      was lower for FCSEMSs (240 days vs 541 days for USEMSs; P = .031). Adverse events
      occurred with 19 FCSEMSs (26.4%) and 10 USEMSs (13.2%); P = .061. The main causes
      of FCSEMS dysfunction were migration (7% vs 0% in the USEMS group) and early
      occlusion mainly because of sludge or overgrowth; late stent occlusion because of
      tumor ingrowth occurred in 13.2% of patients in the USEMS group. There were no
      significant differences either in levels of conjugated bilirubin improvement or
      in overall survival between the FCSEMS and USEMS groups. Median survival was 134
      days in the FCSEMS group and 112 days in the USEMS group (P = .23). CONCLUSION:
      The number of stent-related adverse events was higher, although not
      significantly, among patients in the FCSEMS group. FCSEMSs had a significantly
      higher rate of migration than USEMSs, and stent occlusion occurred earlier. A
      significant difference in the patency rate was observed in favor of the USEMS
      group. (Clinical trial registration number: NCT02102984.).

PMID- 29653121
TI  - Integration and Diagnostic Accuracy of 3T Nonendorectal coil Prostate Magnetic
      Resonance Imaging in the Context of Active Surveillance.
AB  - OBJECTIVE: To evaluate the integration of 3T nonendorectal coil multiparametric
      prostate magnetic resonance imaging (mpMRI) at 2 high-volume practices that
      routinely use mpMRI in the setting of active surveillance. MATERIALS AND METHODS:
      This was an institutional review board-approved, Health Insurance Portability and
      Accountability Act-compliant, and dual-institution retrospective cohort study.
      Subjects undergoing 3T mpMRI without endorectal coil at either study institution
      over a 13-month period (August 1, 2015-August 31, 2016) were selected based on
      predefined criteria: clinical T1/T2 Gleason 6 prostate cancer, prostate-specific
      antigen <15 ng/mL, >=40 years old, mpMRI within 2 years of prostate biopsy, and
      Prostate Imaging Reporting and Data System (PI-RADS) v2 score assigned. Subjects
      surveilled for Gleason >=3 + 4 prostate cancer were excluded. The primary outcome
      was detection of Gleason >=3 + 4 prostate cancer on magnetic resonance-ultrasound
      fusion biopsy, standard biopsy, or prostatectomy within 6 months following mpMRI.
      Positive predictive values (PPVs) were calculated. RESULTS: A total of 286
      subjects (N = 193 from institution 1, N = 93 from institution 2) met the
      criteria. Most (87% [90 of 104]) with maximum PI-RADS v2 scores of 1-2 did not
      receive immediate biopsy or treatment and remained on active surveillance.
      Incidence and PPVs for PI-RADS v2 scores of >=3 were the following: PI-RADS 3 (n
      = 57 [20%], PPV 21% [6 of 29]), PI-RADS 4 (n = 96 [34%], PPV 51% [39 of 77]), and
      PI-RADS 5 (n = 29 [13%], PPV 71% [20 of 28]). No Gleason >=4 + 3 prostate cancer
      was identified for PI-RADS v2 scores of 1-3 (0 of 43 with histology). Following
      mpMRI and subsequent biopsy, 21% (61 of 286) of subjects were removed from active
      surveillance and underwent definitive therapy. CONCLUSION: The 3T nonendorectal
      coil mpMRI has been integrated into the care of patients on active surveillance
      and effectively stratifies risk of Gleason >=3 + 4 prostate cancer in this
      population.

PMID- 29653122
TI  - New trials and results in systemic treatment of HCC.
AB  - The design of prospective trials in hepatocellular carcinoma is a true challenge
      because the underlying condition of the liver, upon drug exposure, could interact
      with the specific course of carcinoma and influence overall outcome. The
      information generated by basic and clinical researchers provides the rationale
      for improving the prognosis of this complex disease. However, an additional
      challenge is interpreting emerging data in real time in order to integrate them
      into the design of further trials. Analysing recent results in detail may
      contribute to improving trial design and analysis, expediting the translation of
      a novel agent's potential benefit, assessed in prospective interventions, to
      clinical practice. This review summarises the data already known and discusses
      newly available results, along with ongoing systemic trials in hepatocellular
      carcinoma treatment.

PMID- 29653123
TI  - Long noncoding RNA lncHand2 promotes liver repopulation via c-Met signaling.
AB  - BACKGROUND & AIMS: Long noncoding RNAs (lncRNAs) play important roles in various
      biological processes, regulating gene expression by diverse mechanisms. However,
      how lncRNAs regulate liver repopulation is unknown. Herein, we aimed to identify
      lncRNAs that regulate liver repopulation and elucidate the signaling pathways
      involved. METHODS: Herein, we performed 70% partial hepatectomy in wild-type and
      gene knockout mice. We then performed transcriptomic analyses to identify a
      divergent lncRNA termed lncHand2 that is highly expressed during liver
      regeneration. RESULTS: LncHand2 is constitutively expressed in the nuclei of
      pericentral hepatocytes in mouse and human livers. LncHand2 knockout abrogates
      liver regeneration and repopulation capacity. Mechanistically, lncHand2 recruits
      the Ino80 remodeling complex to initiate expression of Nkx1-2 in trans, which
      triggers c-Met (Met) expression in hepatocytes. Finally, knockout of both Nkx1-2
      and c-Met causes more severe liver injury and poorer repopulation ability. Thus,
      lncHand2 promotes liver repopulation via initiating Nkx1-2-induced c-Met
      signaling. CONCLUSIONS: Our findings reveal that lncHand2 acts as a critical
      mediator regulating liver repopulation. It does this by inducing Nkx1-2
      expression, which in turn triggers c-Met signaling. LAY SUMMARY: Long noncoding
      RNAs play important roles in various biological processes. While long noncoding
      RNAs do not directly code proteins, they can regulate gene expression by diverse
      mechanisms. We identified the long noncoding RNA, termed lncHand2 because of its
      proximity to the gene Hand2, to be an important determinant of liver regeneration
      through c-Met signaling.

PMID- 29653125
TI  - Mesothelioma and other lung disease in taconite miners; the uncertain role of non
      asbestiform EMP.
AB  - The purpose of this paper was to assess the role of non-asbestiform amphibole
      EMPs in the etiology of mesotheliomas and other lung disease in taconite (iron
      ore) miners. Increased mesothelioma rates have been described in Minnesota
      taconite workers since the late 1990s. Currently, over 100 cases have been
      reported by the Minnesota Department of Health within the complete cohort of
      miners in Minnesota. Geologic sampling has indicated that only the eastern part
      of the iron range contains non-asbestiform amphibole elongate mineral particles
      (EMPs), in close proximity to the ore. This type of EMP has been less studied and
      also exists in talc and gold mining. A series of investigations into the state's
      taconite industry have been recently completed. Results from a cohort mortality
      study indicated an SMR of 2.77 (95% CI = 1.87-3.96) for mesothelioma. In a case
      control study, the odds ratio for mesothelioma for high vs. low EMP exposure was
      2.25 (5% CI = 1.13-4.5) but EMPs in this study were counted by phase contrast
      microscopy. Odds ratios were not elevated in mines located in the eastern part of
      the Mesabi iron range. The overall findings suggest that mesothelioma in taconite
      miners is related to EMP exposure. Because of the way EMPs were counted, results
      from these studies cannot allow a firm conclusion about the association between
      EMP exposure and the reported excess mesothelioma.

PMID- 29653124
TI  - Doxorubicin triggers bioenergetic failure and p53 activation in mouse stem cell
      derived cardiomyocytes.
AB  - Doxorubicin (DOX) is a widely used anticancer drug that could be even more
      effective if its clinical dosage was not limited because of delayed
      cardiotoxicity. Beating stem cell-derived cardiomyocytes are a preferred in vitro
      model to further uncover the mechanisms of DOX-induced cardiotoxicity. Our
      objective was to use cultured induced-pluripotent stem cell(iPSC)-derived mouse
      cardiomyocytes (Cor.At) to investigate the effects of DOX on cell and
      mitochondrial metabolism, as well as on stress responses. Non-proliferating and
      beating Cor.At cells were treated with 0.5 or 1 MUM DOX for 24 h, and
      morphological, functional and biochemical changes associated with mitochondrial
      bioenergetics, DNA-damage response and apoptosis were measured. Both DOX
      concentrations decreased ATP levels and SOD2 protein levels and induced p53
      dependent caspase activation. However, differential effects were observed for the
      two DOX concentrations. The highest concentration induced a high degree of
      apoptosis, with increased nuclear apoptotic morphology, PARP-1 cleavage and
      decrease of some OXPHOS protein subunits. At the lowest concentration, DOX
      increased the expression of p53 target transcripts associated with mitochondria
      dependent apoptosis and decreased transcripts related with DNA-damage response
      and glycolysis. Interestingly, cells treated with 0.5 MUM DOX presented an
      increase in PDK4 transcript levels, accompanied by an increase in phospho-PDH and
      decreased PDH activity. This was accompanied by an apparent decrease in basal and
      maximal oxygen consumption rates (OCR) and in basal extracellular acidification
      rate (ECAR). Cells pre-treated with the PDK inhibitor dichloroacetate (DCA), with
      the aim of restoring PDH activity, partially recovered OCR and ECAR. The results
      suggest that the higher DOX concentration mainly induces p53-dependent apoptosis,
      whereas for the lower DOX concentration the cardiotoxic effects involve
      bioenergetic failure, unveiling PDH as a possible therapeutic target to decrease
      DOX cardiotoxicity.

PMID- 29653126
TI  - Mitochondria in the nervous system: From health to disease, part II.
AB  - In Part II of this Special Issue on "Mitochondria in the Nervous System: From
      Health to Disease", the editors bring together more reviews and original articles
      from researchers in the field of mitochondrial metabolism in the healthy and
      diseased nervous system. Subjects span from basic mitochondrial physiology to
      papers on mitochondrial dynamics and to those altered states of the nervous
      system that can be considered "mitopathologies". Finally, a few papers approach
      aspects of mitochondrial biology linked to the feasibility and validity of a
      mitochondrial therapy.

PMID- 29653127
TI  - Evaluation of early chronic functional outcomes and their relationship to pre
      frontal cortex and hippocampal pathology following moderate-severe traumatic
      brain injury.
AB  - TBI is a significant risk factor for the development of dementia, with the
      interaction between structural damage from TBI and neuroinflammation potentially
      driving this relationship. This study investigated the early chronic post-TBI
      neuroinflammatory response and its relationship to both neurodegenerative
      pathology and functional impairment up to 3 months post-injury. Sprague-Dawley
      rats underwent either sham surgery or the Marmarou model of diffuse moderate
      severe TBI. At 1-month and 3-months post-injury, a functional battery
      encompassing motor function, depressive-like behaviour, anxiety and cognition was
      performed. Western blot and immunohistochemical analysis assessed a range of
      inflammatory, neurodegenerative and oxidative stress markers. At both 1 and 3
      months post injury, depressive-like behaviour was significantly increased in TBI
      animals, with TBI animals also exhibiting impaired cognitive flexibility at 3
      months, although learning and memory remained intact. This was accompanied by a
      significant decrease in markers of synaptic integrity and astrocytic and
      microglia number within the pre-frontal cortex at 1-month post-injury, although
      this resolved by 3-months post-injury. In contrast, minimal pathology was evident
      within the hippocampus at 1 month, with only a decrease in neurofilament-light
      seen at 3 months post-injury. Thus, following a moderate-severe diffuse injury,
      the pre-frontal cortex is most vulnerable to early neuro-structural changes.
      While these changes are resolved at 3 months post-injury, future studies should
      investigate whether they re-emerge or progress to other areas, such as the
      hippocampus, at later time points, which could predispose individuals to the
      development of dementia.

PMID- 29653129
TI  - Delivering drugs to the lungs: The history of repurposing in the treatment of
      respiratory diseases.
AB  - The repurposing of drug delivery by the pulmonary route has been applied to
      treatment and prophylaxis of an increasingly wide range of respiratory diseases.
      Repurposing has been most successful for the delivery of inhaled bronchodilators
      and corticosteroids in patients with asthma and chronic obstructive pulmonary
      disease (COPD). Repurposing utilizes the advantages that the pulmonary route
      offers in terms of more targeted delivery to the site of action, the use of
      smaller doses, and a lower incidence of side-effects. Success has been more
      variable for other drugs and treatment indications. Pulmonary delivery is now
      well established for delivery of inhaled antibiotics in cystic fibrosis (CF), and
      in the treatment of pulmonary arterial hypertension (PAH). Other inhaled
      treatments such as those for idiopathic pulmonary fibrosis (IPF), lung transplant
      rejection or tuberculosis may also become routine. Repurposing has progressed in
      parallel with the development of new drugs, inhaler devices and formulations.

PMID- 29653130
TI  - Complex sparse spatial filter for decoding mixed frequency and phase coded steady
      state visually evoked potentials.
AB  - BACKGROUND: Mixed frequency and phase coding (FPC) can achieve the significant
      increase of the number of commands in steady-state visual evoked potential-based
      brain-computer interface (SSVEP-BCI). However, the inconsistent phases of the
      SSVEP over channels in a trial and the existence of non-contributing channels due
      to noise effects can decrease accurate detection of stimulus frequency. NEW
      METHOD: We propose a novel command detection method based on a complex sparse
      spatial filter (CSSF) by solving l1- and l2,1-regularization problems for a mixed
      coded SSVEP-BCI. In particular, l2,1-regularization (aka group sparsification)
      can lead to the rejection of electrodes that are not contributing to the SSVEP
      detection. RESULTS: A calibration data based canonical correlation analysis (CCA)
      and CSSF with l1- and l2,1-regularization cases were demonstrated for a 16-target
      stimuli with eleven subjects. The results of statistical test suggest that the
      proposed method with l1- and l2,1-regularization significantly achieved the
      highest ITR. COMPARISON WITH EXISTING METHODS: The proposed approaches do not
      need any reference signals, automatically select prominent channels, and reduce
      the computational cost compared to the other mixed frequency-phase coding (FPC)
      based BCIs. CONCLUSIONS: The experimental results suggested that the proposed
      method can be usable implementing BCI effectively with reduce visual fatigue.

PMID- 29653128
TI  - Serotonin-specific lesions of the dorsal raphe disrupt maternal aggression and
      caregiving in postpartum rats.
AB  - The behavioral modifications associated with early motherhood, which include high
      aggression, caring for the young, and low anxiety, are all affected by acute
      pharmacological manipulation of serotonin signaling. However, the effects on all
      these behaviors of permanently disrupting serotonin signaling from one of its
      primary sources, the dorsal raphe nucleus (DR), have not been examined in detail.
      To address this, serotonin-specific lesions centered on the dorsomedial DR (DRdm;
      DR subregion strongly implicated in emotional behaviors) were induced at mid
      pregnancy (day 15) or early postpartum (day 2) in rats using a saporin-conjugated
      neurotoxin targeting the serotonin transporter (Anti-SERT-SAP). Prepartum or
      postpartum Anti-SERT-SAP reduced DRdm serotonin immunoreactivity by ~40-65%, and
      postpartum Anti-SERT-SAP also reduced it in the ventromedial and lateral wings of
      the DR, as well as in the median raphe. Serotonin-immunoreactive fibers were
      significantly reduced in the anterior hypothalamus, but not medial preoptic area,
      of lesioned dams. Pre- or postpartum lesions both greatly reduced maternal
      aggression, but while prepartum lesions did not affect later undisturbed maternal
      caregiving, the larger postpartum lesions prevented the postpartum decline in
      kyphotic nursing and reduced pup licking. Serotonin lesions did not affect pup
      retrieval, but the prepartum lesions temporarily increased maternal hovering over
      and licking the pups observed immediately after the disruptive retrieval tests.
      Dams' anxiety-like behaviors and litter weight gains were unaffected by the
      lesions. These findings suggest that DRdm serotonin projecting to the AH is
      particularly critical for maternal aggression, but that more widespread
      disruption of midbrain raphe serotonin is necessary to greatly impair maternal
      caregiving. Postpartum anxiety may rely more on other neurochemical systems or
      different midbrain serotonergic cell populations.

PMID- 29653132
TI  - Sofosbuvir inhibits hepatitis A virus replication in vitro assessed by a cell
      based fluorescent reporter system.
AB  - Hepatitis A virus (HAV) infection remains a major cause of acute hepatitis
      worldwide and even leads to fulminant hepatitis. For screening antivirals against
      HAV in vitro, we develop a cell-based fluorescent reporter system named Huh-7.5.1
      GA, in which HAV infection is visualized by green fluorescence protein (GFP)
      translocation from the cytosol into the nucleus. The reliability of Huh-7.5.1-GA
      for antiviral studies is validated by IFN-alpha, a known inhibitor of HAV
      replication, which impedes GFP translocation. Utilizing this in-vitro reporter
      system, we find that sofosbuvir, an FDA approved prodrug for the treatment of
      chronic hepatitis C, disturbs GFP translocation and inhibits HAV replication
      efficiently. In addition, we find that inhibition of HAV by sofosbuvir is hepatic
      cell dependent, with IC50 (half-maximal inhibitory concentration) being 6.3 MUM
      and 9.9 MUM in Huh-7.5.1, quantified separately by RT-qPCR and image-based
      analysis. Therefore, our reporter system may serve as a high-throughput platform
      for screening potent antivirals against HAV. Sofosbuvir may be considered for
      treatment of hepatitis A, especially in re-infected patients who undergo liver
      transplantation due to HAV-induced liver failure.

PMID- 29653131
TI  - BET bromodomain inhibitors show anti-papillomavirus activity in vitro and block
      CRPV wart growth in vivo.
AB  - The DNA papillomaviruses infect squamous epithelium and can cause persistent,
      benign and sometimes malignant hyperproliferative lesions. Effective antiviral
      drugs to treat human papillomavirus (HPV) infection are lacking and here we
      investigate the anti-papillomavirus activity of novel epigenetic targeting drugs,
      BET bromodomain inhibitors. Bromodomain and Extra-Terminal domain (BET) proteins
      are host proteins which regulate gene transcription, they bind acetylated lysine
      residues in histones and non-histone proteins via bromodomains, functioning as
      scaffold proteins in the formation of transcriptional complexes at gene
      regulatory regions. The BET protein BRD4 has been shown to be involved in the
      papillomavirus life cycle, as a co-factor for viral E2 and also mediating viral
      partitioning in some virus types. We set out to study the activity of small
      molecule BET bromodomain inhibitors in models of papillomavirus infection.
      Several BET inhibitors reduced HPV11 E1^E4 mRNA expression in vitro and topical
      therapeutic administration of an exemplar compound I-BET762, abrogated CRPV
      cutaneous wart growth in rabbits, demonstrating translation of anti-viral effects
      to efficacy in vivo. Additionally I-BET762 markedly reduced viability of HPV16
      infected W12 cells compared to non-infected C33A cells. The molecular mechanism
      for the cytotoxicity to W12 cells is unknown but may be through blocking viral
      dependent cell-survival factors. We conclude that these effects, across multiple
      papillomavirus types and in vivo, highlight the potential to target BET
      bromodomains to treat HPV infection.

PMID- 29653133
TI  - Rapid MALDI-TOF-based identification of Brucella melitensis from positive blood
      culture vials may prevent laboratory-acquired infections.

PMID- 29653134
TI  - The optimal ethanol lock therapy regimen for treatment of biofilm-associated
      catheter infections: an in-vitro study.
AB  - BACKGROUND: Ethanol-based lock therapy (LT) solutions are used as an alternative
      to antibiotics for the conservative management of catheter-related bloodstream
      infection. However, no clear consensus on regimen or dose has been reached. AIM:
      To find the ethanol-based lock solution containing a sufficiently low
      concentration of ethanol for reduction of the metabolic activity of bacterial and
      fungal biofilms. METHODS: Using an in-vitro model, three concentrations of
      ethanol (25%, 40%, 70%) were tested, with and without 60 IU of heparin, at six
      different time-points and against 24 h preformed biofilms of Staphylococcus
      aureus ATCC29213, Staphylococcus epidermidis (clinical isolate), Enterococcus
      faecalis ATCC33186, Candida albicans ATCC14058, and Escherichia coli ATCC25922.
      The reduction in the metabolic activity of the biofilm was measured using the
      tetrazolium salt assay and LT was considered to be successful when metabolic
      activity fell by >90%. Regrowth inhibition was then tested within 24 h and seven
      days after each LT regimen only at the ethanol concentration of the most
      successful LT regimen. FINDINGS: The most successful LT was achieved with 40%
      ethanol + 60 IU of heparin only at 24, 72, and 24 h for seven-day regimens (P <
      0.05). However, none of the regimens reached 45% RI within seven days of therapy.
      CONCLUSION: According to our in-vitro data, an ethanol-based lock solution with
      40% ethanol + 60 IU heparin administered daily for 72 h is sufficient to almost
      eradicate the metabolic activity of bacterial and fungal biofilms. Future studies
      are needed to study cell regrowth after LT.

PMID- 29653135
TI  - Are red, yellow, green, and blue perceptual categories?
AB  - This study investigated categorical perception for unique hues in order to
      establish a relationship between color appearance, color discrimination, and low
      level (second-stage) mechanisms. We tested whether pure red, yellow, green, and
      blue, (unique hues) coincide with troughs, and their transitions (binary hues)
      with peaks of sensitivity in DKL-space. Results partially confirmed this idea:
      JNDs demarcated perceptual categories at the binary hues around green, blue and
      less clearly around yellow, when colors were isoluminant with the background and
      when accounting for the overall variation of sensitivity by fitting an ellipse.
      The categorical JND pattern for those three categories was in line with the
      effect of the second-stage mechanisms. In contrast, the results for unique red,
      binary red-yellow, and the JNDs for dark colors clearly contradicted categorical
      perception. There was a JND maximum around the center of red and JNDs strongly
      decreased away from the center. Although this observation alone would also be in
      line with categorical perception; unique red was shifted away from the center
      towards yellow so that unique red was close to the minimum instead of the maximum
      JND, hence contradicting categorical perception. In addition, we also showed that
      observers do not adjust unique hues more consistently than binary hues,
      confirming a previous study. Taken together, our findings suggest that some of
      the unique hues could be inherent in the early stages of color processing. At the
      same time, they also raise questions about complex effects of lightness, chroma
      and instructions on the measurements of JNDs and unique hues.

PMID- 29653136
TI  - A regional composite-face effect for species-specific recognition: Upper and
      lower halves play different roles in holistic processing of monkey faces.
AB  - Using a composite-face paradigm, we examined the holistic processing induced by
      Asian faces, Caucasian faces, and monkey faces with human Asian participants in
      two experiments. In Experiment 1, participants were asked to judge whether the
      upper halves of two faces successively presented were the same or different. A
      composite-face effect was found for Asian faces and Caucasian faces, but not for
      monkey faces. In Experiment 2, participants were asked to judge whether the lower
      halves of the two faces successively presented were the same or different. A
      composite-face effect was found for monkey faces as well as for Asian faces and
      Caucasian faces. Collectively, these results reveal that own-species (i.e., own
      race and other-race) faces engage holistic processing in both upper and lower
      halves of the face, but other-species (i.e., monkey) faces engage holistic
      processing only when participants are asked to match the lower halves of the
      face. The findings are discussed in the context of a region-based holistic
      processing account for the species-specific effect in face recognition.

PMID- 29653137
TI  - Hyperactivity and memory/learning deficits evoked by developmental exposure to
      nicotine and/or ethanol are mitigated by cAMP and cGMP signaling cascades
      activation.
AB  - Pregnant smoking women are frequently episodic drinkers. Here, we investigated
      whether ethanol exposure restricted to the brain growth spurt period when
      combined with chronic developmental exposure to nicotine aggravates
      memory/learning deficits and hyperactivity, and associated cAMP and cGMP
      signaling disruption. To further investigate the role of these signaling
      cascades, we verified whether vinpocetine (a phosphodiesterase inhibitor)
      ameliorates the neurochemical and behavioral outcomes. Swiss mice had free access
      to nicotine (NIC, 50 MUg/ml) or water to drink during gestation and until the 8th
      postnatal day (PN8). Ethanol (ETOH, 5 g/kg, i.p.) or saline were injected in the
      pups every other day from PN2 to PN8. At PN30, animals either received
      vinpocetine (20 mg/kg, i.p.) or vehicle before being tested in the step-down
      passive avoidance or open field. Memory/learning was impaired in NIC, ETOH and
      NIC + ETOH mice, and vinpocetine mitigated ETOH- and NIC + ETOH-induced deficits.
      Locomotor hyperactivity identified in ETOH and NIC + ETOH mice was ameliorated by
      vinpocetine. While cyclic nucleotides levels in cerebral cortex and hippocampus
      were reduced by NIC, ETOH and NIC + ETOH, this outcome was more consistent in the
      latter group. As observed for behavior, vinpocetine normalized NIC + ETOH
      nucleotides levels. pCREB levels were also increased in response to vinpocetine,
      with stronger effects in the NIC + ETOH group. Exposure to both drugs of abuse
      worsens behavioral and neurochemical disruption. These findings and the
      amelioration of deleterious effects by vinpocetine support the idea that cAMP and
      cGMP signaling contribute to nicotine- and ethanol-induced hyperactivity and
      memory/learning deficits.

PMID- 29653138
TI  - Neuroprotective action of 4-Hydroxyisophthalic acid against paraquat-induced
      motor impairment involves amelioration of mitochondrial damage and
      neurodegeneration in Drosophila.
AB  - Neurodegenerative disorders including Parkinson's disease (PD) are believed to be
      caused by oxidative stress and mitochondrial dysfunction. Exposure to
      environmental agents such as pesticides has been implicated in the etiology of
      sporadic PD. Paraquat (PQ), a widely used herbicide, induces PD symptoms in
      laboratory animals including Drosophila. PQ acts as a free radical generator and
      induces oxidative damage, which is implicated in neuronal cell death. Drosophila
      model of PQ-induced PD offers a convenient tool for mechanistic studies and, to
      assess the neuroprotective potential of natural antioxidants. We have
      investigated the neuroprotective potential of 4-Hydroxyisophthalic acid (DHA-I),
      a novel bioactive molecule from the roots of Decalepis hamiltonii, against PQ
      induced locomotor impairment and neurodegeneration in Drosophila melanogaster.
      Our study shows that PQ treatment results in movement disorder associated with
      oxidative stress-mediated mitochondrial damage and neurodegeneration in the brain
      as evident by ultrastructural observations. Treatment with DHA-I markedly
      attenuated locomotor deficits, oxidative stress, mitochondrial damage, and
      neurodegenerative changes induced by PQ in Drosophila. Our results show that DHA
      I could be a promising natural antioxidant and a neuroprotective molecule
      targeting oxidative stress-mediated mitochondrial dysfunction with therapeutic
      potential for neurodegenerative disorders.

PMID- 29653139
TI  - Influence of zinc oxide quantum dots in the antibacterial activity and
      cytotoxicity of an experimental adhesive resin.
AB  - OBJECTIVE: To evaluate the influence of zinc oxide quantum dots (ZnOQDs) into an
      experimental adhesive resin regarding the antibacterial activity against
      Streptococcus mutans and the cytotoxicity against pulp fibroblasts. MATERIALS AND
      METHODS: ZnOQDs were synthesized by sol-gel process and were incorporated into 2
      hydroxyethyl methacrylate (HEMA). An experimental adhesive resin was formulated
      by mixing 66.6 wt.% bisphenol A glycol dimethacrylate (BisGMA) and 33.3 wt.% HEMA
      with a photoinitiator system as control group. HEMA containing ZnOQDs was used
      for test group formulation. For the antibacterial activity assay, a direct
      contact inhibition evaluation was performed with biofilm of Streptococcus mutans
      (NCTC 10449). The cytotoxicity assay was performed by Sulforhodamine B (SRB)
      colorimetric assay for cell density determination using pulp fibroblasts. Data
      were analyzed by Student's t-test (alpha = 0.05). RESULTS: The antibacterial
      activity assay indicated statistically significant difference between the groups
      (p = 0.003), with higher values of biofilm formation on the polymerized samples
      of control group and a reduction of more than 50% of biofilm formation on ZnOQDs
      group. No difference of pulp fibroblasts viability was found between the
      adhesives (p = 0.482). CONCLUSION: ZnOQDs provided antibacterial activity when
      doped into an experimental adhesive resin without cytotoxic effect for pulp
      fibroblasts. Thus, the use of ZnOQDs is a strategy to develop antibiofilm
      restorative polymers with non-agglomerated nanofillers. CLINICAL SIGNIFICANCE:
      ZnOQDs are non-agglomerated nanoscale fillers for dental resins and may be a
      strategy to reduce biofilm formation at dentin/restoration interface with no
      cytotoxicity for pulp fibroblasts.

PMID- 29653140
TI  - In vitro mechanical stimulation facilitates stress dissipation and sealing
      ability at the conventional glass ionomer cement-dentin interface.
AB  - OBJECTIVE: The aim of this study was to evaluate the induced changes in the
      chemical and mechanical performance at the glass-ionomer cement-dentin interface
      after mechanical load application. METHODS: A conventional glass-ionomer cement
      (GIC) (Ketac Bond), and a resin-modified glass-ionomer cement (RMGIC) (Vitrebond
      Plus) were used. Bonded interfaces were stored in simulated body fluid, and then
      tested or submitted to the mechanical loading challenge. Different loading
      waveforms were applied: No cycling, 24 h cycled in sine or loaded in sustained
      hold waveforms. The cement-dentin interface was evaluated using a nano-dynamic
      mechanical analysis, estimating the complex modulus and tan delta. Atomic Force
      Microscopy (AFM) imaging, Raman analysis and dye assisted confocal microscopy
      evaluation (CLSM) were also performed. RESULTS: The complex modulus was lower and
      tan delta was higher at interfaces promoted with the GIC if compared to the RMGIC
      unloaded. The conventional GIC attained evident reduction of nanoleakage.
      Mechanical loading favored remineralization and promoted higher complex modulus
      and lower tan delta values at interfaces with RMGIC, where porosity,
      micropermeability and nanoleakage were more abundant. CONCLUSIONS: Mechanical
      stimuli diminished the resistance to deformation and increased the stored energy
      at the GIC-dentin interface. The conventional GIC induced less porosity and
      nanoleakage than RMGIC. The RMGIC increased nanoleakage at the porous interface,
      and dye sorption appeared within the cement. Both cements created amorphous and
      crystalline apatites at the interface depending on the type of mechanical
      loading. CLINICAL SIGNIFICANCE: Remineralization, lower stress concentration and
      resistance to deformation after mechanical loading improved the sealing of the
      GIC-dentin interface. In vitro oral function will favor high levels of
      accumulated energy and permits micropermeability at the RMGIC-dentin interface
      which will become remineralized.

PMID- 29653141
TI  - Dual mechanism of type VII collagen transfer by bone marrow mesenchymal stem cell
      extracellular vesicles to recessive dystrophic epidermolysis bullosa fibroblasts.
AB  - Recessive dystrophic epidermolysis bullosa (RDEB) is a severe blistering disease
      resulting from a lack of type VII collagen production. Recent clinical trials
      have shown efficacy of bone marrow-derived mesenchymal stem cells (BM-MSCs) in
      the treatment of epidermolysis bullosa, including improved basement membrane
      restructuring and cutaneous wound healing. The mechanism as to how type VII
      collagen is transferred from donor stem cell to recipient RDEB cells has not been
      defined. Here, we submit the model that BM-MSC-derived extracellular vesicles
      serve at least two roles: 1) to help transport type VII collagen within the
      extracellular space; and 2) to feed RDEB fibroblasts with messenger RNA that
      codes for type VII collagen, resulting in COL7A1 translation and synthesis of
      type VII collagen alpha chain proteins by RDEB fibroblasts. Utilizing a
      chemoselective ligation detection method, we found RDEB cells that were treated
      simultaneously with BM-MSC EVs and an l-methionine analog, l-homopropargylglycine
      (HPG), synthesized collagen VII alpha chain protein that contained the alkyne
      group of HPG to react (i.e. undergo the Click-iT(r) reaction) with azide-modified
      Alexa 594, suggesting de novo synthesis of type VII collagen by RDEB fibroblasts.
      Thus, our results support a model in which BM-MSC EVs help increase type VII
      collagen levels available to recipient cells by 1) donating BM-MSC type VII
      collagen protein and 2) inducing RDEB fibroblasts to make their own type VII
      collagen protein. These findings allow us to hypothesize that the secretome of BM
      MSCs could have therapeutic value in the treatment of RDEB-related skin
      disorders.

PMID- 29653142
TI  - Characterization of a conjunctival melanoma cell line CM-AS16, newly-established
      from a metastatic Han Chinese patient.
AB  - Conjunctival melanoma (CM) is associated with metastases formation, can be fatal,
      and occurs in all different races. While cell lines are essential for
      experimental research, all available CM cell lines are derived from Caucasian
      patients. Furthermore, they are not derived from metastases. We aimed to
      establish a new CM cell line from a parotid metastasis in a Han Chinese patient
      and to depict its characteristics. The novel cell line, CM-AS16, was obtained
      from a surgical parotid sample and determined as a unique one with short tandem
      repeat (STR) analysis. It has been successively sub-cultured in vitro for more
      than 100 passages and exhibits rapid proliferation and migration. Chromosome
      analysis shows abundant chromosome aberrations, while whole exome sequencing
      (WES) reveals a typical NRAS mutation (Q61R). In vivo tumor growth was
      successfully established in a NOD/SCID mice model, and the immunophenotypes, such
      as HMB45, Melan A, S100, SOX10 and Ki67, manifested similar between the original
      tumor and the xenograft by immunohistochemistry. A MEK inhibitor binimetinib
      prominently suppressed in vitro cell growth by inhibiting ERK1/2 phosphorylation.
      In addition, monoclonal cells were used to demonstrate the drug sensitivity of
      different cells. In conclusion, the first cell line, CM-AS16, that is derived
      from a CM in a Han Chinese patient has highly malignant characteristics and a
      typical NRAS mutation. It may be used as a tool for further exploration of the
      molecular mechanisms of CM.

PMID- 29653143
TI  - Phenotypic characterization of the SIRC (Statens Seruminstitut Rabbit Cornea)
      cell line reveals a mixed epithelial and fibroblastic nature.
AB  - The aim of the present study was to investigate, in the Statens Seruminstitut
      Rabbit Cornea (SIRC) cell line, the presence of epithelial and fibroblastic
      markers, comparing their levels with those of the human Retinal Pigmented
      Epithelial (ARPE-19) cell line, and the Human Keratocyte (HK) cell line,
      respectively. SIRC cells, often described as of epithelial origin, are used as a
      corneal epithelial barrier model to study the permeability of ophthalmic drugs.
      However, they show a morphology that is more consistent with a fibroblastic cell
      phenotype, similar to corneal keratocytes. Our comparative analyses of cell type
      specific markers demonstrated that SIRC do not express cytokeratins 19 and 16
      (typical of ARPE-19) and cytokeratin 9 (typical of HK); they do express
      cytokeratins 3 and 18 common to all three cell lines, and cytokeratin 12 typical
      of ARPE-19. Tight junction proteins were absent in HK, and lower in SIRC than in
      ARPE-19. All cell lines expressed the markers lumican and vimentin, with SIRC
      expressing intermediate levels between HK and ARPE-19; alpha-SMA was highly
      expressed in all lines. These markers, considered typical of fibroblasts, can be,
      however, expressed by epithelial cells during wound healing. These results might
      suggest that long-term in vitro cultivation of cell lines leads to a derangement
      of their specific phenotype, most likely due to genetic and epigenetic factors.
      This could be the reason why SIRC cells came to exhibit a hybrid nature between
      epithelial and fibroblastic cells.

PMID- 29653144
TI  - An Infiltrating Pancreatic Mass.

PMID- 29653145
TI  - Development of Endoscopy- Gastroenterology Diamond Jubilee Review.

PMID- 29653146
TI  - The Answer Is in the Ampulla.

PMID- 29653148
TI  - Advances in Endoscopic Therapy.

PMID- 29653147
TI  - Artificial Intelligence-Assisted Polyp Detection for Colonoscopy: Initial
      Experience.

PMID- 29653149
TI  - A Case of Constipation That Passed From Father to Son.

PMID- 29653150
TI  - Validation of reference genes for quantitative gene expression analysis in
      Ralstonia pseudosolanacearum CQPS-1 under environment stress.
AB  - Quantitative real-time reverse transcriptase PCR (qRT-PCR) has become the method
      choice for quantification of gene expression changes, however, the accuracy of
      the method depends on the stability of reference genes. Ralstonia
      pseudosolanacearum (R. pseudosolanacearum) is an important plant pathogen,
      infecting >450 plant species and causing bacterial wilt. In order to identify
      stable reference genes in R. pseudosolanacearum CQPS-1 under different
      environment stresses. We used five tools (?Ct method, GeNorm, NormFinder,
      BestKeeper, and RefFinder) to evaluate the stability of seven candidate reference
      genes including phosphoglycerate kinase (PGK), glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH), 16S ribosomal RNA (16S), cell division protein ftsZ
      (ftsZ), DNA gyrase subunit A (gyrA), Ribosomal protein L13 (rplM), and
      phosphoserine aminotransferase (serC) under biotic (growth phases) and abiotic
      stress (temperature, hydroxycoumarins, nutrition). Overall, gyrA and serC were
      the most stable genes under different growth phases, while serC, gyrA and ftsZ
      during temperature stress, gyrA, ftsZ and 16S under hydroxycoumarins stress, and
      serC and 16S under nutrition stress conditions. This study provides useful
      resources for normalizing expression changes of target genes in R.
      pseudosolanacearum subjected to environment stress.

PMID- 29653151
TI  - Selective decline in the prevalence of slowly adapting type I mechanoreceptors
      during development.
AB  - Merkel nerve endings are identified physiologically as slowly adapting type I
      mechanoreceptor units. They are important for fine acuity tactile perception. We
      examined the effect of age on the electrophysiological availability of different
      types of slowly adapting mechanoreceptor units. Using 6-50 week old rats, we
      observed an obvious decline with age in the probability of recording from St I
      units of the deep vibrissal nerve. The precipitous decline occurred between ages
      6-14 weeks and then stabilized. By contrast, the prevalence of St II units, the
      other type of slowly adapting mechanoreceptor, remained constant over the age
      range studied. These observations correlate with anatomical findings reported
      elsewhere.

PMID- 29653152
TI  - Low-dose Norfloxacin-treated leptospires induce less IL-1beta release in J774A.1
      cells following discrepant leptospiral gene expression.
AB  - Currently, accumulating evidence is challenging subtherapeutic therapy. Low-dose
      Norfloxacin (Nor) has been reported to suppress the immune response and worsen
      leptospirosis. In this study, we investigated the influence of low-dose Nor (0.03
      MUg/ml, 0.06 MUg/ml, 0.125 MUg/ml) on leptospiral gene expression and analyzed
      the immunomodulatory effects of low-dose Nor-treated leptospires in J774A.1
      cells. To study the expression profiles of low-dose Nor-treated leptospires, we
      chose LipL71/LipL21 as reference genes determined by the geNorm applet in this
      experiment. The results showed that low-dose Nor up-regulated the expression of
      FlaB and inhibited the expression of 16S rRNA, LipL32, LipL41, Loa22, KdpA, and
      KdpB compared with the untreated leptospires. These results indicated that low
      dose Nor could regulate leptospiral gene expression. Using RT-PCR, the gene
      expression of IL-1beta and TNF-alpha in J774A.1 cells was detected. Nor-treated
      leptospires induced higher expression levels of both IL-1beta and TNF-alpha.
      However, when analyzed by ELISA, the release of mature IL-1beta was reduced
      compared with that observed in cells induced with no Nor-treated leptospires,
      although the TNF-alpha protein level showed no significant change. Our study
      indicated that the gene expression of leptospires could be modulated by low-dose
      Nor, which induced less IL-1beta release in J774A.1 cells.

PMID- 29653153
TI  - Unmanned aerial vehicles (drones) to prevent drowning.
AB  - BACKGROUND: Drowning literature have highlighted the submersion time as the most
      powerful predictor in assessing the prognosis. Reducing the time taken to provide
      a flotation device and prevent submersion appears of paramount importance.
      Unmanned aerial vehicles (UAVs) can provide the location of the swimmer and a
      flotation device. OBJECTIVE: The objective of this simulation study was to
      evaluate the efficiency of a UAV in providing a flotation device in different sea
      conditions, and to compare the times taken by rescue operations with and without
      a UAV (standard vs UAV intervention). Several comparisons were made using
      professional lifeguards acting as simulated victims. A specifically-shaped UAV
      was used to allow us to drop an inflatable life buoy into the water. RESULTS:
      During the summer of 2017, 28 tests were performed. UAV use was associated with a
      reduction of time it took to provide a flotation device to the simulated victim
      compared with standard rescue operations (p < 0.001 for all measurements) and the
      time was reduced even further in moderate (81 +/- 39 vs 179 +/- 78 s; p < 0.001)
      and rough sea conditions (99 +/- 34 vs 198 +/- 130 s; p < 0.001). The times taken
      for UAV to locate the simulated victim, identify them and drop the life buoy were
      not altered by the weather conditions. CONCLUSION: UAV can deliver a flotation
      device to a swimmer safely and quickly. The addition of a UAV in rescue
      operations could improve the quality and speed of first aid while keeping
      lifeguards away from dangerous sea conditions.

PMID- 29653154
TI  - Association between intra- and post-arrest hyperoxia on mortality in adults with
      cardiac arrest: A systematic review and meta-analysis.
AB  - OBJECTIVES: The association between intra-arrest and post-arrest hyperoxia and
      mortality in adults with cardiac arrest (CA) is widely debated. We therefore
      conducted a systematic review and meta-analysis to investigate the association
      between intra-arrest and post-arrest hyperoxia and mortality in adults with CA.
      METHODS: We systematically searched MEDLINE and Cochrane databases to identify
      observational studies from January 2008 to December 2017 investigating the
      relationship between hyperoxia (either intra-arrest or post-arrest) and mortality
      in adults with CA. RESULTS: We included 16 observational studies with a total of
      40,573 adult patients. Six studies included patients only with out-of-hospital CA
      (OHCA), 2 studies included patients only with in-hospital CA (IHCA), and 8
      studies included patients with both OHCA and IHCA. Two studies assessed intra
      arrest hyperoxia while 14 studies examined post-arrest hyperoxia. Of the 10
      studies included for quantitative analysis, intra-arrest hyperoxia was associated
      with a significantly lower mortality rate [odds ratio (OR) 0.25, 95% confidence
      interval (CI) 0.12-0.53, p < 0.001] while post-arrest hyperoxia was associated
      with higher mortality (OR 1.34, 95%CI 1.08-1.67, p = 0.008). CONCLUSIONS: In
      adults with CA, intra-arrest hyperoxia is associated with lower mortality while
      post-arrest hyperoxia is associated with higher mortality.

PMID- 29653155
TI  - Chemodiversity of Cirsium fruits: Antiproliferative lignans, neolignans and
      sesquineolignans as chemotaxonomic markers.
AB  - While analyzing the fruit composition of nine European Cirsium species
      representing three sections (i.e., Cephalonoplos, Chamaeleon and Eriolepis), four
      lignans, three neolignans and three sesquineolignans were determined and used as
      chemotaxonomic markers. Among them, desmethyl balanophonin and desmethyl
      picrasmalignan were determined for the first time in the plant kingdom, as the
      main metabolites of the Chamaeleon section. Prebalanophonin and
      prepicrasmalignan, identified so far exclusively in C. eriophorum, were also
      confirmed in C. boujartii and C. vulgare, highlighting the chemotaxonomic
      significance of these compounds in the Eriolepis section. The antiproliferative
      assay of the compounds isolated from their optimum sources, confirmed a dose
      dependent inhibitory effect of the structures bearing the 4',7-epoxy moiety
      (balanophonin, picrasmalignan, desmethyl balanophonin, desmethyl picrasmalignan)
      against SW480 colon cancer cells, while those bearing the 4',7-dihydroxy motif
      (prebalanophonin, prepicrasmalignan) were inactive.

PMID- 29653156
TI  - Oestrous phase cyclicity influences judgment biasing in rats.
AB  - The identification of cognitive bias has become an important measure of animal
      welfare. Negative cognitive biases develop from a tendency for animals to process
      novel information pessimistically. Judgment-bias testing is the commonplace
      methodology to detect cognitive biases. However, concerns with these methods have
      been frequently-reported; one of which being the discrepancy between male and
      female cognitive expression. The current study assessed the factors of social
      status and oestrus, to investigate whether oestrous cycle rotation, or
      subordination stress encouraged an increase in pessimistic responses. Female
      Sprague-Dawley rats (n = 24) were trained on an active-choice judgment bias
      paradigm. Responses to the ambiguous probe were recorded as optimistic or
      pessimistic. Oestrous phase was determined by assessing vaginal cytology in
      stained vaginal cell smears. Rats in the dioestrous phase and those rats
      considered to be subordinate demonstrated an increased percentage of pessimistic
      responses. However, no interaction between these factors was observed. This
      suggests that oestrous cyclicity can influence the judgment biases of female
      animals; a previously unreported finding. On this basis, researchers should be
      encouraged to account for both oestrous phase cyclicity and social status as an
      additional fixed effect in study design.

PMID- 29653157
TI  - Do depressive symptoms affect balance in older adults with mild cognitive
      impairment? Results from the "gait and brain study".
AB  - BACKGROUND: Mild cognitive impairment (MCI) and depression independently affect
      balance control in older adults. However, it is uncertain whether depressive
      symptoms would amplify balance problems in older adults with MCI. AIM: To
      evaluate if the presence of significant depressive symptoms affects postural sway
      under somatosensory challenges in a MCI population. METHODS: Eighty two
      participants (mean of 75.3 +/- 6.4 years of age; 46% women) with MCI completed
      cognitive and balance assessments. Participants were grouped by severity of
      depressive symptoms using the Geriatric Depression Scale-15, as MCI with
      depressive symptoms (MCI-D = 14, score >= 5) and MCI without depressive symptoms
      (MCI = 68, score < 5). Postural sway area was evaluated during eyes open (EO) and
      eyes closed (EC) while standing on a rigid flat force plate platform, and
      compared across groups. Analyses were controlled for age, sex, comorbidities,
      anti-depressant medication use, executive function, and baseline sway. RESULTS:
      MCI-D showed larger postural sway area when compared with MCI irrespective of
      visual feedback conditions (p = 0.03). This difference remained significant after
      adjusting for anti-depressant use and executive function performance. The lack of
      interaction between groups and visual condition was associated with group
      differences in postural sway during EO condition (Beta = 0.08, CI -257.5-621.9; p
      = 0.41) and by comparable sway increase from EO to EC in both groups. CONCLUSION:
      Depressive symptoms in individuals with MCI worsened postural stability during
      both eyes open and eyes closed conditions independently of cognitive function.
      Significant depressive symptoms may affect balance in MCI populations,
      potentially increasing the risk of falls.

PMID- 29653159
TI  - Phosphorylation-induced changes in the energetic frustration in human Tank
      binding kinase 1.
AB  - Tank binding kinase 1 (TBK-1) plays an important role in immunity, inflammation,
      autophagy, cell growth and proliferation. Nevertheless, a key molecular and
      structural detail of TBK-1 phosphorylation and activation has been largely
      unknown. Here we investigated the energy landscape of phosphorylated (active) and
      unphosphorylated (inactive) forms of human TBK-1 to characterize the interplay
      between phosphorylation and local frustration. By employing the algorithm
      equipped with energy function and implemented in Frustratometer web-server
      (http://www.frustratometer.tk), we quantify the role of frustration in the
      activation of TBK-1. Accordingly, the conformational changes were observed in
      phosphoregulated active and inactive TBK-1. Substantial changes in frustration,
      flexibility and interatomic motions were observed among different forms of TBK-1.
      Structurally rigid kinase domain constitutes a minimally frustrated hub in the
      core of the catalytic domain, and highly frustrated clusters mainly at the C-lobe
      might enable the conformational transitions during activation. Also, a large
      network of highly frustrated interactions is found in the SDD domain of TBK-1
      involved in protein-protein interactions and dimerization. The contact maps of
      the activation loop and alpha-C helix of kinase domain showed significant changes
      upon phosphorylation. Cross correlation analysis indicate that both intra and
      inter subunit correlated motions increases with phosphorylation of TBK-1.
      Phosphorylation thus introduces subtle changes in long-range contacts that might
      lead to significant conformational change of TBK-1.

PMID- 29653158
TI  - Mice deficient in AKAP13 (BRX) develop compulsive-like behavior and increased
      body weight.
AB  - OBJECTIVE: Hormonal contributions to the sex-dependent development of both
      obsessive-compulsive disorder (OCD) and obesity have been described, but the
      underlying mechanisms are incompletely understood. A-kinase anchoring protein 13
      (AKAP13) significantly augments ligand-dependent activation of estrogen receptors
      alpha and beta. The hypothalamus and pituitary gland are implicated in the
      development and exacerbation of OCD and obesity and have strong AKAP13
      expression. The AKAP13 localization pattern observed in these key brain regions
      together with its effects on sex steroid action suggest a potential role for
      AKAP13 in compulsive-like behaviors. Here we tested the role of AKAP13 in
      compulsive-like behavior and body weight using an Akap13 haploinsufficient murine
      model. MATERIALS AND METHODS: Targeted deletion of the Akap13 gene generated
      haploinsufficient (Akap13+/-) mice in a C57BL6/J genetic background. Established
      behavioral assays were conducted, video recorded, and scored blindly to assess
      compulsive-like behavior based on genotype and gender. Tests included: marble
      burying, grooming, open- field and elevated plus-maze. Brain and body weights
      were also obtained. Mean levels of test outcomes were compared using multi-way
      ANOVA to test for genotype, sex, genotype*sex, and genotype*sex*age interaction
      effects with Bonferroni adjustment for multiple comparisons, to further explain
      any significant interactions. RESULTS: The marble-burying and grooming assays
      revealed significant sex-dependent increases in perseverative, compulsive-like
      behaviors in female Akap13 haploinsufficient mice compared to female wild type
      (WT) mice by demonstrating increased marble-burying activity (p = .0025) and a
      trend towards increased grooming behavior (p = .06). Male Akap13
      haploinsufficient mice exhibited no behavioral changes (p > 0.05). Elevated plus
      maze and open-field test results showed no overt anxiety-like behavior in Akap13
      haploinsufficient mice irrespective of sex (p > 0.05, both). No differences in
      brain weight were found in Akap13 haploinsufficient mice compared to WT mice (p >
      0.05). However, female Akap13 haploinsufficient mice weighed more than female WT
      mice in the 4 to <7 months age range (p = .0051). Male Akap13 haploinsufficient
      mice showed no differences in weight compared to male WT mice (p = >0.05) at any
      age range examined. CONCLUSION: Akap13 haploinsufficiency led to sex-dependent,
      compulsive-like behavioral changes in a murine model. Interestingly, Akap13
      haploinsufficiency also led to a sex-dependent increase in body weight. These
      results revealed a requirement for AKAP13 in murine behavior, particularly in
      female mice, and is the first report of AKAP13 involvement in murine behavior.
      Future studies may examine the involvement of AKAP13 in the pathophysiology of
      OCD in female humans and may contribute to a better understanding of the role of
      AKAP13 and sex hormones in the development and exacerbation of OCD.

PMID- 29653160
TI  - A computational model for the joint onset and development.
AB  - Joints connect the skeletal components and enable movement. The appearance and
      development of articulations is due to different genetic, biochemical, and
      mechanical factors. In the embryonic stage, controlled biochemical processes are
      critical for organized growth. We developed a computational model, which predicts
      the appearance, location, and development of joints in the embryonic stage.
      Biochemical events are modeled with reaction diffusion equations with generic
      molecules representing molecules that 1) determine the site where the
      articulation will appear, 2) promote proliferation, and matrix synthesis, and 3)
      define articular cartilage. Our model accounts for cell differentiation from
      mesenchymal cells to pre-cartilaginous cells, then cartilaginous cells, and
      lastly articular cartilage. These reaction-diffusion equations were solved using
      the finite elements method. From a mesenchymal 'bud' of a phalanx, the model
      predicts growth, joint cleavage, joint morphology, and articular cartilage
      formation. Our prediction of the gene expression during development agrees with
      molecular expression profiles of joint development reported in literature. Our
      computational model suggests that initial rudiment dimensions affect diffusion
      profiles result in Turing patterns that dictate sites of cleavage thereby
      determining the number of joints in a rudiment.

PMID- 29653161
TI  - Is Routine Renal Tumor Biopsy Associated with Lower Rates of Benign Histology
      following Nephrectomy for Small Renal Masses?
AB  - PURPOSE: Renal tumor biopsies have been proposed as a management alternative to
      avoid treatment of benign or low risk small renal masses. However, many
      urologists are reluctant to recommend renal tumor biopsy because they feel its
      result frequently will not impact management. Our primary objective was to
      evaluate if centers that routinely favor renal tumor biopsy have lower rates of
      benign histology after surgery than centers where a selective renal tumor biopsy
      approach is used. MATERIALS AND METHODS: This was a retrospective multicenter
      study of patients who underwent partial or radical nephrectomy for a lesion
      suspicious for localized renal cell carcinoma which measured 4 cm or less (cT1a
      and pT1a or pT3a) between 2013 and 2015. A logistic regression model was used to
      examine whether the odds of obtaining a benign tumor following surgery differed
      between centers that routinely favor renal tumor biopsy and centers where a
      selective renal tumor biopsy approach is used. RESULTS: A total of 542 small
      renal masses in 516 patients were included in study. The rate of histologically
      benign tumors after surgery was 11%. This rate was significantly lower at centers
      that routinely favor renal tumor biopsy than at centers where a selective renal
      tumor biopsy approach is used (5% vs 16%, p <0.001). On multivariable analysis
      older age, smaller tumors and centers where a selective renal tumor biopsy
      approach is used were significantly associated with greater odds of finding a
      histologically benign tumor postoperatively. Compared to centers that routinely
      favor renal tumor biopsy the odds of finding a benign tumor at surgery was 4
      times more likely at centers where a selective renal tumor biopsy approach is
      used (OR 4.1, 95% CI 1.9-8.3). CONCLUSIONS: Routine renal tumor biopsy reduces
      surgery for benign tumors and the potential for short-term and long-term
      morbidity associated with these procedures. This study suggests that routine
      renal tumor biopsy may be a valuable tool to decrease overtreatment of small
      renal masses.

PMID- 29653162
TI  - Inconsistency in the Definition of Urinary Tract Infection after Intravesical
      Botulinum Toxin A Injection: A Systematic Review.
AB  - PURPOSE: To more accurately examine the rate of urinary tract infection following
      onabotulinumtoxinA injection of the bladder we systematically reviewed the
      literature for definitions of urinary tract infection in studies of
      onabotulinumtoxinA injections. We assessed the studies for consistency with
      guideline statements defining urinary tract infections. MATERIALS AND METHODS: We
      systematically reviewed the literature by querying MEDLINE(r) and Embase(r). We
      included original studies on adult patients with idiopathic overactive bladder
      and/or neurogenic detrusor overactivity who underwent cystoscopy with
      onabotulinumtoxinA injection and in whom urinary tract infection was a reported
      outcome. RESULTS: We identified 299 publications, of which 50 met study inclusion
      criteria. In 27 studies (54%) urinary tract infection diagnostic criteria were
      defined with a total of 10 definitions among these studies. None of the
      overactive bladder studies used a definition which met the EAU (European
      Association of Urology) criteria for urinary tract infection. Only 2 of the 10
      studies on patients with neurogenic bladder used a urinary tract infection
      definition consistent with the NIDRR (National Institute on Disability and
      Rehabilitation Research) standards. CONCLUSIONS: Definitions of urinary tract
      infection are heterogeneous and frequently absent in the literature on
      onabotulinumtoxinA to treat overactive bladder and/or neurogenic bladder. Given
      the potential for post-procedure urinary symptoms in this setting, explicit
      criteria are imperative to establish the true urinary tract infection rate
      following treatment with onabotulinumtoxinA.

PMID- 29653164
TI  - Authors' Reply.

PMID- 29653163
TI  - Epstein-Barr Virus as a Potential Etiology of Persistent Bladder Inflammation in
      Human Interstitial Cystitis/Bladder Pain Syndrome.
AB  - PURPOSE: Interstitial cystitis/bladder pain syndrome is characterized by bladder
      inflammation without bacterial infection. Although viral infection is a potential
      etiological cause, few studies have been reported. MATERIALS AND METHODS: Bladder
      specimens were obtained from patients with interstitial cystitis/bladder pain
      syndrome and from patients with stress urinary incontinence as controls. Bladder
      specimens were tested for Epstein-Barr encoded RNAs by in situ hybridization and
      for Epstein-Barr DNA by quantitative real-time polymerase chain reaction,
      serology and immunohistochemical staining. RESULTS: Enrolled in study were 16
      patients with interstitial cystitis/bladder pain syndrome and Hunner lesions, 23
      without interstitial cystitis/bladder pain syndrome or Hunner lesions and 10
      controls. The positive rate of Epstein-Barr encoded RNA on in situ hybridization
      in bladder specimens from patients with vs without interstitial cystitis/bladder
      pain syndrome and Hunner lesions was 50% vs 8.6%. No Epstein-Barr encoded RNA was
      found in control specimens. On quantitative real-time polymerase chain reaction
      Epstein-Barr DNA was detected in 68.8% vs 16.7% of bladder specimens in patients
      with vs without interstitial cystitis/bladder pain syndrome and Hunner lesions.
      The median viral load was 1,836 copies per ml (range 216 to 75,144). Only 1
      control specimen was Epstein-Barr positive on quantitative real-time polymerase
      chain reaction. All serum samples from patients with interstitial
      cystitis/bladder pain syndrome showed past Epstein-Barr viral infection. Epstein
      Barr infection was present in 87.5% vs 17.4% of bladder specimens from patients
      with vs without interstitial cystitis/bladder pain syndrome and Hunner lesions
      for a total of 46.2% with interstitial cystitis/bladder pain syndrome.
      Immunohistochemical staining of CD3 and CD20 revealed that Epstein-Barr infection
      was mainly restricted to T lymphocytes in bladders showing interstitial
      cystitis/bladder pain syndrome. CONCLUSIONS: Bladder Epstein-Barr infection in T
      cells may be linked to the pathogenesis of persistent inflammation in patients
      with interstitial cystitis/bladder pain syndrome.

PMID- 29653165
TI  - Comment on: Cancer Pain With a Neuropathic Component: A Cross-sectional Study of
      Its Clinical Characteristics, Associated Psychological Distress, Treatments, and
      Predictors at Referral to a Cancer Pain Clinic.

PMID- 29653166
TI  - Adverse Events Caused by Aspiration Implemented for Death Rattle in Patients in
      the Terminal Stage of Cancer: A Retrospective Observational Study.

PMID- 29653167
TI  - Adnexal Torsion.
AB  - Adnexal torsion is an uncommon gynecologic disorder caused by the partial or
      complete rotation of the ovary and/or the fallopian tube on its vascular support.
      Delay in treatment can impact fertility adversely. The objective of this report
      is to provide clinical recommendations based on the latest evidence. Specifically
      we discuss epidemiology, clinical presentation, diagnostic approach and
      management of adnexal torsion in adolescents.

PMID- 29653168
TI  - Purification, partial characterization and inducing tumor cell apoptosis activity
      of a polysaccharide from Ganoderma applanatum.
AB  - In this study, a homogeneous polysaccharide (designated as GAP-3S) with an
      average molecular weight of 6.82*105 Da was purified from Ganoderma applanatum.
      GAP-3S was composed of glucose, galactose, fucose and xylose in the molar ratio
      of 7.1:2.6:1.1:1. It could significantly inhibit the proliferation of MCF-7 cells
      in a dose- and time-dependent manner. Flow cytometry analysis indicated that GAP
      3S could also induce cell apoptosis. Treatment of MCF-7 cells with GAP-3S lead to
      the collapse of mitochondrial membrane potential and the accumulation of ROS, up
      regulated expression of Bax, cleavage of PARP, p-p38 and p-JNK, and the down
      regulated expression of Bcl-2, PARP and p-ERK. The activities of caspase-3 and
      caspase-9 were also increased in GAP-3S-treated MCF-7 cells compared to untreated
      cells. These findings suggested that GAP-3S probably induced apoptosis in MCF-7
      cells through intrinsic mitochondrial apoptosis and MAPK signaling pathways.

PMID- 29653169
TI  - Nanoencapsulation of lemon essential oil in Chitosan-Hicap system. Part 1: Study
      on its physical and structural characteristics.
AB  - Lemon essential oils (LEOs) as a bioactive compound with health beneficial
      potential are used as safe additives in foods, medicine and nutritional
      supplements. However, it is a chemical compound which is sensitive to light,
      thermal condition and oxidation. To overcome these challenge encapsulation could
      be an adequate technique to protect them from degradation and evaporation. In
      this study, nanocapsules based on chitosan (CS) and modified starch (Hicap) with
      LEOs as an active ingredient was prepared by freeze-drying. The produced
      nanocapsules were characterized by their structural and physicochemical
      properties. It was found that nanocapsules produced by using CS: Hi-cap
      (1.5%:8.5%) clearly showed the highest encapsulation efficiency (85.44%) and Zeta
      potential value (+44.23mV). In vitro release studies demonstrated a prolonged
      release of the samples with larger CS ratio. Most nanocapsules sizes ranged from
      339.3 to 553.3nm. The obtained nanocapsules showed a rough surface without the
      spherical shape as represented by Scanning electron microscopy images.
      Differential scanning calorimetry (DSC) thermogram and Fourier transform infrared
      (FTIR) spectroscopy techniques confirmed the success of LEOs encapsulation. The
      desirable physicochemical properties and thermal stability specified that such
      nanocapsules have promising application in delivery of LEOs in medicine and food
      industries.

PMID- 29653170
TI  - Ascorbic acid prevents cellular uptake and improves biocompatibility of chitosan
      nanoparticles.
AB  - Chitosan nanoparticles have many applications, such as gene and drug delivery,
      due to their biocompatibility. Chitosan nanoparticles are currently produced by
      dissolution in acetic acid that affects the biocompatibility at acidic pH. Here,
      we synthesized and characterized chitosan (CS) and ascorbate chitosan (AsCS)
      nanoparticles and investigated their cytotoxic effects, internalization, and
      distribution in the human colon carcinoma cell line using confocal laser scanning
      microscopy (CLSM). The CS and AsCS nanoparticles were spherical with average
      particle sizes of 44+/-8.4nm and 87+/-13.6nm, respectively. CS nanoparticles were
      taken up by the cells and showed dose-dependent cytotoxicity. By contrast, AsCS
      nanoparticles were not internalized and showed no cytotoxicity. Therefore, AsCS
      nanoparticles are more biocompatible than CS nanoparticles and may be more
      suitable for extracellular drug delivery.

PMID- 29653171
TI  - Production of biological nanoparticles from bovine serum albumin as controlled
      release carrier for curcumin delivery.
AB  - This study described a curcumin (CUR) loaded bovine serum albumin nanoparticles
      (BSA@CUR NPs), which could solubilize the poorly water-soluble drug and increase
      the therapeutic efficacy of the drug. BSA@CUR NPs were synthesized by a simple
      coacervation procedure. The resultant BSA@CUR NPs showed a spherical shape, with
      a diameter of 92.59+/-16.75nm (mean +/- SD) nm and a zeta-potential of - 9.19mV.
      The in vitro drug release study of CUR showed a sustained and controlled release
      pattern. Cellular toxicity of BSA NPs was also investigated on HFF2 cell lines.
      Additionally, a hemolysis test of as prepared NPs were performed for
      investigation of hemocompatibility. Hemolysis assay and cytotoxicity study
      results on HFF-2 cell line show that as prepared BSA NPs are biocompatible. The
      in vitro anticancer activity of the BSA@CUR NPs were performed by MTT assay on
      MCF-7 cancer cells. These results suggest that BSA@CUR NPs are a new drug
      delivery system for cancer therapy.

PMID- 29653172
TI  - Characterization, antioxidant activity and hepatoprotective effect of purple
      sweetpotato polysaccharides.
AB  - In this study, three kinds of polysaccharides (named PSWP, PSAP-1 and PSAP-2)
      were successively isolated from purple sweetpotato tubers by hot water, 0.5M and
      2M sodium hydroxide solutions. The characterization, in vitro antioxidant
      activity and in vivo hepatoprotective effect of these polysaccharides were
      investigated. Results indicated that PSWP, PSAP-1 and PSAP-2 were all beta-type
      polysaccharides containing different contents of uronic acid, protein and
      polyphenol. Both PSWP and PSAP-1 were composed by arabinose, glucose and
      galactose, whereas PSAP-2 was consisted of arabinose, rhamnose and glucose. All
      the polysaccharides exhibited moderate 2,2-diphenyl-1-picrylhydrazyl (DPPH)
      radical scavenging activity and reducing power. As compared with
      tetrachloromethane (CCl4) treatment group, mice administrated with PSWP, PSAP-1
      and PSAP-2 exhibited decreased levels of serum enzymes (alkaline phosphatase,
      alanine transaminase and aspartate transaminase) and hepatic lipid peroxidation,
      whereas increased levels of hepatic antioxidant enzymes (superoxide dismutase,
      catalase and glutathione peroxidase) and non-enzymatic antioxidant (glutathione).
      Notably, PSWP displayed stronger antioxidant activity and hepatoprotective effect
      than PSAP-1 and PSAP-2. The hepatoprotective effect of PSWP was comparable to
      positive standard of silymarin. Our results suggested polysaccharides from purple
      sweetpotato possessed potential antioxidant activity and protective effect
      against CCl4-induced acute liver damage.

PMID- 29653173
TI  - Superabsorbent hydrogel based on sulfonated-starch for improving water and saline
      absorbency.
AB  - The agriculture sectors in many developing countries have been suffering from
      water shortage and decreasing crop yields. Thus, an increasing interest has been
      emerged to develop much-needed solutions for a more sustainable management of
      water resources. Agricultural hydrogel that absorbs many times of its weight in
      water has been used to distribute into dry regions in order to improve the soil's
      ability to absorb and retain water. Here, amphoteric superabsorbent hydrogel is
      prepared by indirect method based on anionic starch bearing sulfonate groups.
      Anionic starch derivatives were graft-polymerized with acrylonitrile (AN) and
      hydrolyzed by alkaline by which nitrile groups were converted to hydrophilic
      functional groups. The hydrolyzed sodium starch sulfate-g-polyacrylonitrile (HSSS
      g-PAN) copolymer exhibited improved water and saline absorbencies compared to
      that of native starch-based hydrogel. The co-polymerization was conducted for
      60min polymerization time, 0.75% (wt/wt) ammonium persulfate (APS) associated
      with sodium bisulfite, SBS, (50% (wt/wt) of APS), 65 degrees C for polymerization
      temperature and double molar ratio of acrylonitrile to the starch derivatives.
      The hydrogel based on the sulfonated starch derivatives 1 and 2 showed superior
      water absorbency for both distilled (250% and 190% respectively) and saline (90%
      and 70%) solutions over that of the native starch.

PMID- 29653174
TI  - Molecular detection of Anaplasma phagocytophilum-like Anaplasma spp. and
      pathogenic A. Phagocytophilum in cattle from South Korea.
AB  - Anaplasma phagocytophilum is the causative agent of human granulocytic
      anaplasmosis and tick-borne fever in domestic ruminants. Differential diagnosis
      of zoonotic and pathogenic tick-borne diseases like granulocytic anaplasmosis is
      important for the efficient implementation of control programs. Thus, the
      differentiation of pathogenic A. phagocytophilum from non-pathogenic A.
      phagocytophilum-like (APL) Anaplasma spp. is essential. Recent molecular analyses
      of APL revealed its distinct phylogenetic position from A. phagocytophilum. This
      study was conducted to detect A. phagocytophilum and genetically related strains
      in 764 cattle in South Korea using PCR and restriction fragment length
      polymorphism assays. APL clade A and A. phagocytophilum were identified in 20
      (2.6%) and 16 (2.1%) cattle, respectively, with 16 cattle (2.1%) displaying co
      infection. The 16S rRNA sequences of APL clade A were similar (98.3-99.9%) to
      those clustered in the APL clade A from eastern Asia. The A. phagocytophilum 16S
      rRNA sequence shared 98.6-100% identity to those of the A. phagocytophilum group.
      We used PCR to amplify the groEL and msp2 genes from the 20 samples positive for
      the 16S rRNA gene and found that 16 were positive for the groEL sequences in the
      APL clade A, which showed identity (82.8-84.4%) to those clustered in the APL
      clade A from Japan. Amplification of msp2 was unsuccessful. The co-infection
      results suggested sequence diversity in Anaplasma spp. Till date, both A.
      phagocytophilum and APL have been reported to be distributed separately in
      several animals throughout South Korea. This report is the first co-detection of
      A. phagocytophilum and APL in Korean cattle using molecular methods. Further
      studies are needed to provide additional molecular background and trace the
      evolutionary tree of Anaplasma species in animals and ticks.

PMID- 29653175
TI  - Phylogeny and biogeography of the pantropical genus Zanthoxylum and its closest
      relatives in the proto-Rutaceae group (Rutaceae).
AB  - Zanthoxylum L. (prickly ash) is the only genus in the Citrus L. family (Rutaceae)
      with a pantropical distribution. We present the first detailed phylogenetic and
      biogeographic study of the genus and its close relatives in the proto-Rutaceae
      group. Our phylogenetic analyses based on two plastid and two nuclear markers
      show that the genus Toddalia Juss. is nested within Zanthoxylum, that earlier
      generic and intrageneric classifications need revision, and that the
      homochlamydeous flowers of the temperate species of Zanthoxylum are the result of
      a reduction from heterochlamydeous flowers. The biogeographic analyses reveal a
      Eurasian origin of Zanthoxylum in the Paleocene or Eocene with successive
      intercontinental or long-range migrations. Zanthoxylum likely crossed the North
      Atlantic Land Bridges to colonize the Americas in the Eocene, and migrated back
      to the Old World probably via the Bering Land Bridge in the Oligocene or Miocene.
      Zanthoxylum also colonized several Pacific Islands and the Hawaiian clade shows
      phylogenetic incongruence between the plastid and nuclear datasets, suggesting
      hybridization. The Hawaiian species are one of the rare examples of endemic
      Hawaiian lineages that are older than the current main islands.

PMID- 29653176
TI  - Hyperactive piggyBac transposase improves transformation efficiency in diverse
      insect species.
AB  - Even in times of advanced site-specific genome editing tools, the improvement of
      DNA transposases is still on high demand in the field of transgenesis: especially
      in emerging model systems where evaluated integrase landing sites have not yet
      been created and more importantly in non-model organisms such as agricultural
      pests and disease vectors, in which reliable sequence information and genome
      annotations are still pending. In fact, random insertional mutagenesis is
      essential to identify new genomic locations that are not influenced by position
      effects and thus can serve as future stable transgene integration sites. In this
      respect, a hyperactive version of the most widely used piggyBac transposase
      (PBase) has been engineered. The hyperactive version (hyPBase) is currently
      available with the original insect codon-based coding sequence (ihyPBase) as well
      as in a mammalian codon-optimized (mhyPBase) version. Both facilitate
      significantly higher rates of transposition when expressed in mammalian in vitro
      and in vivo systems compared to the classical PBase at similar protein levels.
      Here we demonstrate that the usage of helper plasmids encoding the hyPBase -
      irrespective of the codon-usage - also strikingly increases the rate of
      successful germline transformation in the Mediterranean fruit fly (Medfly)
      Ceratitis capitata, the red flour beetle Tribolium castaneum, and the vinegar fly
      Drosophila melanogaster. hyPBase-encoding helpers are therefore highly suitable
      for the generation of transgenic strains of diverse insect orders. Depending on
      the species, we achieved up to 15-fold higher germline transformation rates
      compared to PBase and generated hard to obtain transgenic T. castaneum strains
      that express constructs affecting fitness and viability. Moreover, previously
      reported high sterility rates supposedly caused by hyPBase (iPB7), encoded by
      ihyPBase, could not be confirmed by our study. Therefore, we value hyPBase as an
      effective genetic engineering tool that we highly recommend for insect
      transgenesis.

PMID- 29653177
TI  - Additive potential of combination therapy against cryptococcosis employing a
      novel amphotericin B and fluconazole loaded dual delivery system.
AB  - Cryptococcus neoformans is one of the most lethal fungi causing mortality across
      the globe. Immuno-competent patients and patients taking immuno-suppressive
      medications are extremely susceptible to its infection. For effective removal of
      cryptococcal burden, there is an urgent need for new forms of therapy. In the
      present study, we have explored the potential effects of amphotericin B (AMB) and
      fluconazole (FLC) in combination, against cryptococcosis in Swiss albino mice. To
      enhance the therapeutic potential of the tested drugs, they were entrapped into
      fibrin microspheres; a dual delivery vehicle comprising of poly-lactide co
      glycolide (PLGA) microsphere that was additionally encapsulated into the fibrin
      cross-linked plasma bead. Dynamics of fibrin microspheres included survival and
      fungal burden in lung, liver and spleen of treated mice. While each drug was
      effective in combination or alone, prominent additive potential of AMB and FLC
      were clearly observed when used in fibrin microsphere. Significant reduction in
      fungal burden and increase in survival rate of AMB + FLC-fibrin microspheres
      treated mice shows an extensive accessibility of both tested drugs without any
      side-effects. A full potential of two-drug combination encapsulated in fibrin
      microspheres proposes an effective approach of safe delivery to the target site
      in their intact form and decrease the drug associated toxicities.

PMID- 29653178
TI  - Surfactants as stabilizers for biopharmaceuticals: An insight into the molecular
      mechanisms for inhibition of protein aggregation.
AB  - PURPOSE: Surfactants are common stabilizers, often added to biopharmaceuticals
      formulations, but the mechanisms at the basis of their activity are unclear. The
      aim of this work is to provide insight into the molecular factors underlying
      surfactant effectiveness as protectants. METHODS: Molecular Dynamics simulations
      of human growth hormone (hGH) in the presence of Tween 20 were performed. The
      effect of Tween 20 was compared with the activity of commonly used protectants,
      such as the disaccharides. RESULTS: We found that Tween 20 could prevent the self
      association of hGH, leading to the formation of a protein-surfactant complex. In
      the case of unfolded hGH, surfactant molecules were oriented with their
      hydrophilic head in the direction of the protein hydrophobic patches. This
      created a highly unstable situation, fostering refolding. In the case of native
      hGH, Tween 20 molecules oriented with their lipophilic groups in the direction of
      the protein surface. This thermodynamically stabilized the native conformation,
      preventing unfolding. CONCLUSIONS: We found that the ability of surfactants to
      foster protein refolding is related to their amphiphilic nature, and, more
      specifically, to their specific orientation with respect to the protein surface.
      A molecular mechanism explaining surfactant activity is proposed, which could
      provide direction for improvements in biopreservation.

PMID- 29653179
TI  - A distributed computational model for estimating room air level of constituents
      due to aerosol emission from e-vapor product use.
AB  - Most indoor air quality models reported in the literature are well-mixed models.
      A well-mixed model estimates the room average concentration of constituents from
      sources. It does not provide information on (1) how far and how fast the emitted
      chemicals travel in the indoor space? And (2) how the concentration changes as a
      function of distance from the emission source? We developed a distributed model,
      using computational fluid dynamics and thermodynamics principles, which allows
      for aerosol dispersion in an indoor space and includes evaporation and
      condensation of constituents in a multi-compound aerosol mixture. The distributed
      model can estimate the spatial and temporal variations of the concentration of
      individual constituents present in the emitted aerosol in vapor and particulate
      phases separately. Results from the model were compared with the published
      experimental data and were found to be in good agreement. A sensitivity analysis
      was performed to evaluate the impact of various parameters that affect the air
      level of the emitted constituents within an indoor space, including rate of
      emission, the rate of air exchange, etc. The model can also be used to estimate
      the level of second hand exposure in a confined space where e-vapor products
      (EVPs) are used.

PMID- 29653180
TI  - Development and validation of analytical methodology for the quantification of
      aldehydes in e-cigarette aerosols using UHPLC-UV.
AB  - Aldehydes are produced in e-cigarette aerosols, as a result of the thermal
      decomposition of vegetable glycerin, propylene glycerol and flavorings in the
      atomizer. These aldehydes were collected with derivatization into 2,4
      dinitrophenylhydrazine using impinger trapping. A new methodology for
      simultaneous quantitative analysis of aldehydes in base liquids was developed and
      validated. Chromatographic separation was carried out on a Jupiter Proteo 90A
      column, with the mobile phase consisting of 0.1% formic acid in water and
      acetonitrile, at a flow rate of 0.4 mL/min. Linearity was demonstrated over the
      range of concentrations 0.025-10 MUg/mL, with correlation of determination >=
      0.999. Intra- and inter-day % relative standard deviation and relative error were
      <= 10%. The lower limit of detection and quantification were 0.008 and 0.025
      MUg/mL, respectively. This method was further used for the quantification of
      aldehydes emitted by different base liquids. It has been shown that vegetable
      glycerin produces the highest percentage of aldehydes after thermal decomposition
      compared to propylene glycerol. We propose that it can be used for future e
      liquids emissions studies.

PMID- 29653181
TI  - ZH-1 enhances the anticancer activity of gemcitabine via deoxyribonucleotide
      synthesis and apoptotic pathway against A549 cells.
AB  - The purpose of this study was to investigate the inhibitory effect of ZH-1
      ((6S,9aS,6aR,9bR)-6-(phenylcarbonyl)-6,6a,9a,9b-tetrahydro-8H-azolidino[3,4-a]b
      enzo [e]indolizine-7,9-dione) and its potential interaction with gemcitabine in
      A549 cells. MTT assay showed that the combined use of gemcitabine and ZH-1
      presented a significant inhibition effect on A549 cell growth with the cell
      viability from 82.3 +/- 5.6% to 51.0 +/- 6.6%. The CI value was 0.60 suggesting a
      synergistic effect between these two drugs. HPLC-MS/MS data indicated that
      combined treatment with gemcitabine and ZH-1 induced a significant decrease in
      deoxyadenosine triphosphate, deoxycytidine triphosphate, deoxyguanosine
      triphosphate and deoxythymidine triphosphate levels compared with use of
      gemcitabine alone. Five RNs as well as seven dRNs were considered to be
      significantly contributive to the discrimination of samples. Furthermore, western
      blot analysis revealed that the combination treatment caused A549 cell apoptosis
      via the intrinsic pathway by up-regulating Bax/Bcl-2 ratio, activating caspase-9,
      caspase-3 and poly-ADP-ribose polymerase, and promoting caspase-7, caspase-9 and
      poly-ADP-ribose polymerase cleavage. Collectively, the combined treatment with
      gemcitabine and ZH-1 exerted a strong synergistic action on anticancer activity
      through growth inhibition, perturbations in ribonucleotides and
      deoxyribonucleotides and the activation of intrinsic apoptotic signaling pathway.

PMID- 29653182
TI  - Detection of biogenic amines and microbial safety assessment of novel Meju
      fermented with addition of Nelumbo nucifera, Ginkgo biloba, and Allium sativum.
AB  - Meju, a cooked and fermented soy bean based food product, is used as a major
      ingredient in Korean traditional fermented foods such as Doenjang. We developed a
      novel type of Meju using single and combined extracts of Allium sativum (garlic
      clove), Nelumbo nucifera (lotus leaves), and Ginkgo biloba (ginkgo leaves) at 1%
      and 10% concentrations to improve the safety of Meju-based fermented products.
      Biogenic amines (BAs) in protein-rich fermented food products pose considerable
      toxical risks. The objective of this study was to investigate the effects of
      adding selected plant extracts in Meju samples during fermentation. Nine BAs,
      including tryptamine, 2-phenylethylamine, putrescine, cadaverine, agmatine,
      histamine, tyramine, spermidine and spermine, were isolated from Meju samples
      after sample derivatization with dansyl chloride and analyzed by high performance
      liquid chromatography. As a result, all tested Meju samples with added plant
      extracts showed total BAs levels in the range of 20.12 +/- 2.03 to 118.42 +/-
      10.68 mg/100 g, which were below the safety limit set by various regulatory
      authorities (USFDA/KFDA/EFSA). However, among all tested Meju samples, LOM10
      (Meju fermented with Nelumbo nucifera at 10% concentration) showed higher levels
      of BAs content than others either due to batch-to-batch variability or reduced
      beneficial microorganisms and/or due to increase in BA forming microorganisms.
      Also, none of the samples showed the aflatoxin level above the detection limit.
      Furthermore, all the tested Meju samples improved microbial safety as confirmed
      by the complete absence of Salmonella species and Staphylococcus aureus. However,
      some of the Meju samples showed the presence of coliforms (in range of 1.6 * 100
      1.1 * 103 CFU/g), which is under regulatory limits. These results suggested that
      the use of plant extracts in Meju during fermentation have potential to improve
      microbial and toxicological safety of Meju products.

PMID- 29653183
TI  - Atropa belladonna neurotoxicity: Implications to neurological disorders.
AB  - Atropa belladonna, commonly known as belladonna or deadly nightshade, ranks among
      one of the most poisonous plants in Europe and other parts of the world. The
      plant contains tropane alkaloids including atropine, scopolamine, and
      hyoscyamine, which are used as anticholinergics in Food and Drug Administration
      (FDA) approved drugs and homeopathic remedies. These alkaloids can be very toxic
      at high dose. The FDA has recently reported that Hyland's baby teething tablets
      contain inconsistent amounts of Atropa belladonna that may have adverse effects
      on the nervous system and cause death in children, thus recalled the product in
      2017. A greater understanding of the neurotoxicity of Atropa belladonna and its
      modification of genetic polymorphisms in the nervous system is critical in order
      to develop better treatment strategies, therapies, regulations, education of at
      risk populations, and a more cohesive paradigm for future research. This review
      offers an integrated view of the homeopathy and neurotoxicity of Atropa
      belladonna in children, adults, and animal models as well as its implications to
      neurological disorders. Particular attention is dedicated to the
      pharmaco/toxicodynamics, pharmaco/toxicokinetics, pathophysiology,
      epidemiological cases, and animal studies associated with the effects of Atropa
      belladonna on the nervous system. Additionally, we discuss the influence of
      active tropane alkaloids in Atropa belladonna and other similar plants on FDA
      approved therapeutic drugs for treatment of neurological disorders.

PMID- 29653184
TI  - Estrogen alleviates neuropathic pain induced after spinal cord injury by
      inhibiting microglia and astrocyte activation.
AB  - Neuropathic pain after spinal cord injury (SCI) is developed in about 80% of SCI
      patients and there is no efficient therapeutic drug to alleviate SCI-induced
      neuropathic pain. Here we examined the effect of estrogen on SCI-induced
      neuropathic pain at below-level and its effect on neuroinflammation as underlying
      mechanisms. Neuropathic pain is developed at late phase after SCI and a single
      dose of 17beta-estradiol (100, 300 MUg/kg) were administered to rats with
      neuropathic pain after SCI through intravenous injection. As results, both
      mechanical allodynia and thermal hyperalgesia were significantly reduced by
      17beta-estradiol compared to vehicle control. Both microglia and astrocyte
      activation in the lamina I and II of L4-5 dorsal horn was also inhibited by
      17beta-estradiol. In addition, the levels of p-p38MAPK and p-ERK known to be
      activated in microglia and p-JNK known to be activated in astrocyte were
      significantly decreased by 17beta-estradiol. Furthermore, the mRNA expression of
      inflammatory mediators such as Il-1beta, Il-6, iNos, and Cox-2 was more
      attenuated in 17beta-estradiol-treated group than in vehicle-treated group.
      Particularly, we found that the analgesic effect by 17beta-estradiol was mediated
      via estrogen receptors, which are expressed in dorsal horn neurons. These results
      suggest that 17beta-estradiol may attenuate SCI-induced neuropathic pain by
      inhibiting microglia and astrocyte activation followed inflammation.

PMID- 29653185
TI  - Sex differences in the development of hepatic steatosis in cafeteria diet-induced
      obesity in young mice.
AB  - The present study was planned to improve our understanding about sex differences
      in the development of hepatic steatosis in cafeteria diet-induced obesity in
      young mice. Female (FCaf) and male (MCaf) mice fed a cafeteria diet had similar
      body weight gain and adiposity index, but FCaf had a more extensive steatosis
      than MCaf. FCaf livers exhibited a higher non-alcoholic fatty liver disease
      activity score, elevated lipid percentage area (+34%) in Sudan III staining and
      increased TG content (+25%) compared to MCaf. Steatosis in FCaf was not
      correlated with changes in the transcript levels of lipid metabolism-related
      genes, but a reduced VLDL release rate was observed. Signs of oxidative stress
      were found in FCaf livers, as elevated malondialdehyde content (+110%), reduced
      catalase activity (-36%) and increased Nrf2 and Hif1a mRNA expression compared to
      MCaf. Interestingly, fibroblast growth factor 21 (Fgf21) mRNA expression was
      found to be exclusively induced in MCaf, which also exhibited higher FGF21 serum
      levels (+416%) and hepatic protein abundance (+163%) than FCaf. Moreover,
      cafeteria diet increased Fgfr1, Fsp27 and Ucp1 mRNA expression in brown adipose
      tissue of males (MCaf), but not females (FCaf). FGF21 hepatic production by male
      mice seems to be part of a complex network of responses to the nutritional stress
      of the cafeteria diet, probably related to the unfolded protein response
      activation. Although aimed at the restoration of hepatic metabolic homeostasis,
      the branch involving Fgf21 upregulation seems to be impaired in females,
      rendering them incapable of reducing the hepatic lipid content and cellular
      oxidative stress.

PMID- 29653186
TI  - Constraint-induced movement therapy improves efficacy of task-specific training
      after severe cortical stroke depending on the ipsilesional corticospinal
      projections.
AB  - Descending spinal pathways (corticospinal, rubrospinal, and reticulospinal) are
      believed to contribute to functional recovery resulting from rehabilitative
      training after stroke. However, the contribution of each pathway remains unclear.
      In the current study, we investigated rehabilitation-induced functional recovery
      and remodelling of the descending spinal pathways after severe cortical stroke in
      rats followed by 3 weeks of various rehabilitation [constraint-induced movement
      therapy (CIMT), skilled forelimb reaching, rotarod, and treadmill exercise].
      Following photothrombotic stroke, 96% of corticospinal neurons in the
      ipsilesional motor cortex were destroyed. Despite the preservation of 82% of
      total spinal projection neurons (e.g. rubrospinal and reticulospinal projection
      neurons), rats showed persistent and severe disability, especially in skilled
      motor function. In this severe stroke model, only CIMT promoted functional
      recovery, associated with increased corticospinal projections from the peri
      infarct motor cortex. Rehabilitation-induced recovery was reversed when the
      restored corticospinal neurons were destroyed by a second stroke. These data
      indicate that training-induced functional recovery is dependent on ipsilesional
      corticospinal projections, which highlights the importance of using strategies to
      enhance survival, axonal remodelling, or regeneration of corticospinal neurons to
      effectively restore function in severely affected stroke patients.

PMID- 29653187
TI  - Mid-cervical spinal cord contusion causes robust deficits in respiratory
      parameters and pattern variability.
AB  - Mid-cervical spinal cord contusion disrupts both the pathways and motoneurons
      vital to the activity of inspiratory muscles. The present study was designed to
      determine if a rat contusion model could result in a measurable deficit to both
      ventilatory and respiratory motor function under "normal" breathing conditions at
      acute to chronic stages post trauma. Through whole body plethysmography and
      electromyography we assessed respiratory output from three days to twelve weeks
      after a cervical level 3 (C3) contusion. Contused animals showed significant
      deficits in both tidal and minute volumes which were sustained from acute to
      chronic time points. We also examined the degree to which the contusion injury
      impacted ventilatory pattern variability through assessment of Mutual Information
      and Sample Entropy. Mid-cervical contusion significantly and robustly decreased
      the variability of ventilatory patterns. The enduring deficit to the respiratory
      motor system caused by contusion was further confirmed through electromyography
      recordings in multiple respiratory muscles. When isolated via a lesion, these
      contused pathways were insufficient to maintain respiratory activity at all time
      points post injury. Collectively these data illustrate that, counter to the
      prevailing literature, a profound and lasting ventilatory and respiratory motor
      deficit may be modelled and measured through multiple physiological assessments
      at all time points after cervical contusion injury.

PMID- 29653189
TI  - Overreliance link between asthmatic subjects and short-acting beta2 agonists.
AB  - In this brief communication, it was described the overreliance link generated
      between a young asthmatic subject and Short Acting Beta agonist (SABA)
      bronchodilator. It was an attempt to delineate the stages of this conflicting
      link where predominated the overreliance on SABA that might be one of the main
      circumstances surrounding near fatal asthma attack. New approach is needed from
      international guidelines to avoid development of such a problematic link between
      asthmatic subjects and SABA.

PMID- 29653188
TI  - Ketamine reduces deleterious consequences of spreading depolarizations.
AB  - Recent work has implicated spreading depolarization (SD) as a key contributor the
      progression of acute brain injuries, however development of interventions
      selectively targeting SD has lagged behind. Initial clinical intervention efforts
      have focused on observations that relatively high doses of the sedative agent
      ketamine can completely suppress SD. However, blocking propagation of SD could
      theoretically prevent beneficial effects of SD in surrounding brain regions.
      Selective targeting of deleterious consequences of SD (rather than abolition)
      could be a useful adjunct approach, and be achieved with lower ketamine
      concentrations. We utilized a brain slice model to test whether deleterious
      consequences of SD could be prevented by ketamine, using concentrations that did
      not prevent the initiation and propagation of SD. Studies were conducted using
      murine brain slices, with focal KCl as an SD stimulus. Consequences of SD were
      assessed with electrophysiological and imaging measures of ionic and synaptic
      recovery. Under control conditions, ketamine (up to 30 MUM) did not prevent SD,
      but significantly reduced neuronal Ca2+ loading and the duration of associated
      extracellular potential shifts. Recovery of postsynaptic potentials after SD was
      also significantly accelerated. When SD was evoked on a background of mild
      metabolic compromise, neuronal recovery was substantially impaired. Under
      compromised conditions, the same concentrations of ketamine reduced ionic and
      metabolic loading during SD, sufficient to preserve functional recovery after
      repetitive SDs. These results suggest that lower concentrations of ketamine could
      be utilized to prevent damaging consequences of SD, while not blocking them
      outright and thereby preserving potentially protective effects of SD.

PMID- 29653190
TI  - Evaluation of whole genome sequencing and software tools for drug susceptibility
      testing of Mycobacterium tuberculosis.
AB  - OBJECTIVES: Culture-based assays are currently the reference standard for drug
      susceptibility testing for Mycobacterium tuberculosis. They provide good
      sensitivity and specificity but are time consuming. The objective of this study
      was to evaluate whether whole genome sequencing (WGS), combined with software
      tools for data analysis, can replace routine culture-based assays for drug
      susceptibility testing of M. tuberculosis. METHODS: M. tuberculosis cultures sent
      to the Finnish mycobacterial reference laboratory in 2014 (n = 211) were
      phenotypically tested by Mycobacteria Growth Indicator Tube (MGIT) for first-line
      drug susceptibilities. WGS was performed for all isolates using the Illumina
      MiSeq system, and data were analysed using five software tools (PhyResSE, Mykrobe
      Predictor, TB Profiler, TGS-TB and KvarQ). Diagnostic time and reagent costs were
      estimated for both methods. RESULTS: The sensitivity of the five software tools
      to predict any resistance among strains was almost identical, ranging from 74% to
      80%, and specificity was more than 95% for all software tools except for TGS-TB.
      The sensitivity and specificity to predict resistance to individual drugs varied
      considerably among the software tools. Reagent costs for MGIT and WGS were ?26
      and ?143 per isolate respectively. Turnaround time for MGIT was 19 days (range 10
      50 days) for first-line drugs, and turnaround time for WGS was estimated to be 5
      days (range 3-7 days). CONCLUSIONS: WGS could be used as a prescreening assay for
      drug susceptibility testing with confirmation of resistant strains by MGIT. The
      functionality and ease of use of the software tools need to be improved.

PMID- 29653191
TI  - Microbiota transplantation and/or CRISPR/Cas in the battle against antimicrobial
      resistance.

PMID- 29653192
TI  - Synergistic stabilisation of NOsGC by cinaciguat and non-hydrolysable
      nucleotides: Evidence for sGC activator-induced communication between the heme
      binding and catalytic domains.
AB  - Nitric oxide sensitive guanylyl cyclase (NOsGC) is a heterodimeric enzyme
      consisting of one alpha and one beta subunit. Each subunit consists of four
      domains: the N-terminal heme-nitric oxide oxygen binding (HNOX) domain, a PAS
      domain, a coiled-coil domain and the C-terminal catalytic domain. Upon activation
      by the endogenous ligand NO or activating drugs, NOsGC catalyses the conversion
      of GTP to cGMP. Although several crystal structures of the isolated domains are
      known, the structure of the full-length enzyme and the interdomain conformational
      changes during activation remain unsolved to date. In the current study, we
      performed protein thermal shift assays of purified NOsGC to identify discrete
      conformational states amenable to further analysis e.g. by crystallisation. A non
      hydrolysable substrate analogue binding to the catalytic domain led to a subtle
      change in melting temperature. An activator drug binding to the HNOX domain led
      to a small increase. However, the combination of substrate analogue and activator
      drug led to a marked synergistic increase from 51  degrees C to 60  degrees C.
      This suggests reciprocal communication between HNOX domain and catalytic domain
      and formation of a stable activated conformation amenable to further biophysical
      characterization.

PMID- 29653193
TI  - Treatment of periodontitis in smokers with multiple sessions of antimicrobial
      photodynamic therapy or systemic antibiotics: A randomized clinical trial.
AB  - BACKGROUND: The aim of this study was to evaluate the effects of non-surgical
      periodontal therapies on smokers with chronic periodontitis, involving multiple
      adjunctive applications of antimicrobial photodynamic therapy (aPDT), and
      systemic metronidazole (MTZ) with amoxicillin (AMX). METHODS: All participants
      were treated with scaling and root planing (SRP). Seventeen patients received 400
      mg of MTZ and 500 mg of AMX three times per day for 7 days (MTZ + AMX).
      Additionally, 17 patients received a placebo, and 17 patients were treated with
      three applications of aPDT (immediately, 48 h and 96 h after SRP). Clinical and
      microbiological examinations were performed at baseline and at 90 and 180 days
      post-therapy. Subgingival samples were analyzed using real-time polymerase chain
      reaction. RESULTS: After 180 days, the patients in groups MTZ + AMX and aPDT had
      significantly lower mean probing depths, more clinical attachment level gains and
      less bleeding on probing. At 180 days, in the moderate pocket there was a
      reduction in the levels of Porphyromonas gingivalis and Prevotella nigrescens in
      the MTZ + AMX group, while group aPDT showed a reduction in Prevotella
      nigrescens. Furthermore, at 180 days, in the deep pocket a reduction in
      Porphyromonas gingivalis, Prevotella intermedia and Prevotella nigrescens was
      observed in group MTZ + AMX, as well as a reduction in the levels of Prevotella
      intermedia and Prevotella nigrescens in group aPDT. CONCLUSION: In smokers with
      periodontitis, the MTZ + AMX and aPDT treatments significantly improved the
      effects of SRP.

PMID- 29653194
TI  - Chronic agomelatine treatment prevents comorbid depression in the post-status
      epilepticus model of acquired epilepsy through suppression of inflammatory
      signaling.
AB  - Inflammatory signal molecules are suggested to be involved in the mechanism
      underlying comorbid depression in epilepsy. In the present study, we tested the
      hypothesis that the novel antidepressant agomelatine, a potent melatonin MT1 and
      MT2 receptor agonist and serotonin 5HT2C receptor antagonist, can prevent
      depressive symptoms developed during the chronic epileptic phase by suppressing
      an inflammatory response. Chronic treatment with agomelatine (40 mg/kg, i.p.) was
      initiated an hour after the kainate acid (KA)-induced status epilepticus (SE) and
      maintained for a period of 10 weeks in Wistar rats. Registration of spontaneous
      motor seizures was performed through a video (24 h/day) and EEG monitoring.
      Antidepressant activity of agomelatine was explored in the splash test, sucrose
      preference test (SPT) and forced swimming test (FST) while anxiolytic effect was
      observed through the novelty suppression-feeding test (NSFT) during chronic phase
      in epileptic rats. The frequency of motor seizures detected by video and EEG
      recording did not differ between vehicle and Ago group. Rats with registered
      spontaneous motor seizures showed symptoms typical for depressive behavior that
      included decreased grooming, anhedonia during the dark period and hopeless-like
      behavior. Epileptic rats exhibited also anxiety with novelty-induced hypophagia.
      This behavioral deficit correlated with increased signal markers of inflammation
      (plasma levels of interleukin (IL)-1beta and activated glia in brain), while
      plasma corticosterone levels were not changed. Agomelatine treatment during
      epileptogenesis exerted a clear antidepressant effect by suppressing all
      behavioral hallmarks, reducing plasma IL-1beta levels and preventing microgliosis
      and astrogliosis in specific limbic regions. The present results suggest that
      agomelatine treatment starting after SE can provide an effective therapy of
      comorbid depression in chronic epileptic condition through suppression of
      inflammatory signaling.

PMID- 29653195
TI  - Genome-wide Integration Study of Circulating miRNAs and Peripheral Whole-Blood
      mRNAs of Male Acute Ischemic Stroke Patients.
AB  - Several circulating microRNAs (miRNAs) have been proved to serve as stable
      biomarkers in blood for acute ischemic stroke (AIS). However, the functions of
      these biomarkers remain elusive. By conducting the integration analysis of
      circulating miRNAs and peripheral whole-blood mRNAs using bioinformatics methods,
      we explored the biological role of these circulating markers in peripheral whole
      blood at the genome-wide level. Stroke-related circulating miRNA profile data
      (GSE86291) and peripheral whole-blood mRNA expression data (GSE16561) were
      collected from the Gene Expression Omnibus (GEO) datasets. We selected male
      patients to avoid any gender differences in stroke pathology. Male stroke-related
      miRNAs (M-miRNAs) and mRNAs (M-mRNAs) were detected using GEO2R. Nine M-miRNAs
      (five up- and four down-regulated) were applied to TargetScan to predict the
      possible target mRNAs. Next, we intersected these targets with the M-mRNAs (38 up
      and three down-regulated) to obtain the male stroke-related overlapped mRNAs (Mo
      mRNAs). Finally, we analyzed biological functions of Mo-mRNAs using the Gene
      Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), and constructed
      networks among the Mo-mRNAs, overlapped M-miRNAs (Mo-miRNAs), and their
      functions. The Mo-mRNAs were enriched in functions such as platelet
      degranulation, immune response, and pathways associated with phagosome biology
      and Staphylococcus aureus infection. This study provides an integrated view of
      interactions among circulating miRNAs and peripheral whole-blood mRNAs involved
      in the pathophysiological processes of male AIS.

PMID- 29653196
TI  - Transcription Factors in Regulatory and Protein Subnetworks during Generation of
      Neural Stem Cells and Neurons from Direct Reprogramming of Non-fibroblastic Cell
      Sources.
AB  - Direct reprogramming of non-fibroblastic cells to the neuronal cell types
      including induced neurons (iNs) and induced neural stem cells (iNSCs) has
      provided an alternative approach for the direct reprogramming of fibroblasts to
      those cells. However, to increase the efficiency of the reprogramming process the
      underlying mechanisms should be clarified. In the current study, we analyzed the
      gene expression profiles of five different cellular conversions to understand the
      most significant molecular mechanisms and transcription factors (TFs) underlying
      each conversion. For each conversion, we found the list of differentially
      expressed genes (DEGs) and the list of differentially expressed TFs (DE-TFs)
      which regulate expression of DEGs. Moreover, we constructed gene regulatory
      networks based on the TF-binding sites' data and found the most central
      regulators and the most active part of the networks. Furthermore, protein
      complexes were identified from constructed protein-protein interaction networks
      for DE-TFs. Finally, we proposed a list of main regulators for each conversion;
      for example, in the direct conversion of epithelial-like cells (ECs) to iNSCs,
      combination of centrality with active modules or protein complex analyses
      highlighted the role of POU3F2, BACH1, AR, PBX1, SOX2 and NANOG genes in this
      conversion. To the best of our knowledge, this study is the first one that
      analyzed the direct conversion of non-fibroblastic cells toward iNs and iNSCs and
      we believe that the expression manipulation of identified genes may increase
      efficiency of these processes.

PMID- 29653197
TI  - Epidemiologic practice and conduct guidelines: a new kid on the block.

PMID- 29653198
TI  - The M3 multimorbidity index outperformed both Charlson and Elixhauser indices
      when predicting adverse outcomes in people with diabetes.
AB  - OBJECTIVES: Multimorbidity is common among those living with diabetes. The
      purpose of this manuscript was to assess the performance of the recently
      developed M3 multimorbidity index within a large, well-defined cohort of patients
      with diabetes. STUDY DESIGN AND SETTING: We compared regression model performance
      between three morbidity indices (M3, Charlson, and Elixhauser) for important
      adverse outcomes (hospitalization, amputation, and mortality) among 217,207
      patients with diabetes and compared the real-world applied impact of these
      indices for modeling these diabetes outcomes against two key exposure variables
      (ethnicity and deprivation). RESULTS: The M3 Index outperformed both Charlson and
      Elixhauser indices in terms of the prediction of hospitalization events,
      amputation events, and death. When applied to models that were investigating the
      relationship between (a) ethnicity and (b) deprivation on risk of these outcomes,
      the M3 Index also explained more confounding due to multimorbidity than either
      Charlson or Elixhauser (e.g., shift in odds ratio toward the null when predicting
      hospitalization: M3 Index 60%, Charlson 40%, and Elixhauser 24%). CONCLUSION:
      These results give additional support for the utility of the M3 index in clinical
      populations, adding to previous observations regarding its performance in a
      general population setting.

PMID- 29653199
TI  - High agreement was obtained across scores from multiple equated scales for social
      anxiety disorder using item response theory.
AB  - OBJECTIVES: There is no standardized approach to the measurement of social
      anxiety. Researchers and clinicians are faced with numerous self-report scales
      with varying strengths, weaknesses, and psychometric properties. The lack of
      standardization makes it difficult to compare scores across populations that use
      different scales. Item response theory offers one solution to this problem via
      equating different scales using an anchor scale to set a standardized metric.
      This study is the first to equate several scales for social anxiety disorder.
      STUDY DESIGN AND SETTING: Data from two samples (n = 3,175 and n = 1,052),
      recruited from the Australian community using online advertisements, were used to
      equate a network of 11 self-report social anxiety scales via a fixed parameter
      item calibration method. RESULTS: Comparisons between actual and equated scores
      for most of the scales indicted a high level of agreement with mean differences
      <0.10 (equivalent to a mean difference of less than one point on the standardized
      metric). CONCLUSION: This study demonstrates that scores from multiple scales
      that measure social anxiety can be converted to a common scale. Rescoring
      observed scores to a common scale provides opportunities to combine research from
      multiple studies and ultimately better assess social anxiety in treatment and
      research settings.

PMID- 29653200
TI  - A 67-item stress resilience item bank showing high content validity was developed
      in a psychosomatic sample.
AB  - OBJECTIVES: To develop the first item bank to measure stress resilience (SR) in
      clinical populations. STUDY DESIGN AND SETTING: Qualitative item development
      resulted in an initial pool of 131 items covering a broad theoretical SR concept.
      These items were tested in n = 521 patients at a psychosomatic outpatient clinic.
      Exploratory and confirmatory factor analysis, as well as other state-of-the-art
      item analyses and item response theory were used for item evaluation and
      calibration of the final item bank. RESULTS: Of the initial item pool of 131
      items, we excluded 64 items (54 factor loading <0.5, four residual correlations
      >0.3, two nondiscriminative item response curves, and four differential item
      functioning). The final set of 67 items indicated sufficient model fit in
      confirmatory factor analysis and item response theory analyses. In addition, a 10
      item short form with high measurement precision (SE <= 0.32 in a theta range
      between -1.8 and +1.5) was derived. Both the SR item bank and the SR short form
      were highly correlated with an existing static legacy tool (Connor-Davidson
      Resilience Scale). CONCLUSION: The final SR item bank and 10-item short form
      showed good psychometric properties. When further validated, they will be ready
      to be used within a framework of computer-adaptive tests for a comprehensive
      assessment of the stress construct.

PMID- 29653201
TI  - Kinetics of IgM and IgG antibodies after scrub typhus infection and the clinical
      implications.
AB  - OBJECTIVES: The serological detection of IgM antibodies is the most widely used
      test to diagnose scrub typhus infection. However, the kinetics of IgM and IgG
      antibodies post-infection remain elusive, which could contribute to false
      positivity. The objective of this study was to document the nature of the
      evolution of these antibody titres after infection. METHODS: Adult patients
      previously confirmed to have scrub typhus by IgM ELISA, positive PCR, or both,
      were included in this cross-sectional study. The levels of IgM and IgG antibodies
      in serum samples were tested using an ELISA and the distribution curve was
      plotted. RESULTS: Two hundred and three patients were included in this study.
      Post-infection serum sampling was done between 1 month and 46 months after
      documented infection. IgM levels declined gradually but remained elevated above
      the diagnostic cut-off for up to 12 months post-infection. However, IgG levels
      continued to rise reaching a peak at 10 months, followed by a gradual decline
      over several months. In the majority of cases, the IgG levels remained above the
      cut-off threshold for more than 36 months. CONCLUSIONS: Clinicians need to be
      cautious in using a single serum sample for the detection of IgM to diagnose
      scrub typhus, as it remains elevated for up to 12 months after the infection,
      whereas the serum IgG level could be used as an indicator of past infection.

PMID- 29653202
TI  - Clinicopathological features and outcomes of pythiosis.
AB  - OBJECTIVES: Vascular pythiosis is a life-threatening infection caused by the
      oomycete Pythium insidiosum. This article reports the clinical presentation,
      serodiagnosis, pathology, and outcomes seen at the authors' institution. METHODS:
      The cases of patients with proven vascular pythiosis at Ramathibodi Hospital,
      Mahidol University, Bangkok, Thailand from January 2006 to December 2016 were
      analyzed retrospectively. RESULTS: Thirteen patients were analyzed, eight of whom
      had underlying thalassemias. Of the remaining five patients, one had aplastic
      anemia, one had myelodysplasia, one had acute leukemia, one had cirrhosis, and
      one had alcoholism. Neutropenic patients showed a rapid clinical deterioration.
      Atypical presentations including carotid arteritis, aneurysm, brain abscess, and
      stroke occurred in the non-thalassemic patients. Serology yielded positive
      results in all cases, with a rapid turnaround time. Serology has the advantage of
      providing a presurgical diagnosis, which allows prompt surgery and clinical cure
      to be achieved. Pathology revealed a neutrophilic response in the acute phase and
      a later shift to granuloma. Immunotherapy in combination with itraconazole and
      terbinafine was given. The amputation rate was 77%, and disease-free surgical
      margins were achieved in five cases (38%). The mortality rate was 31%.
      CONCLUSIONS: This study highlights new aspects of pythiosis, such as the unusual
      host, clinical presentation, serology as a marker for rapid diagnosis,
      histopathology, and outcomes. Early recognition of the disease with prompt
      multimodality treatment may improve survival.

PMID- 29653203
TI  - Approximate Bayesian algorithm to estimate the basic reproduction number in an
      influenza pandemic using arrival times of imported cases.
AB  - BACKGROUND: In an influenza pandemic, arrival times of cases are a proxy of the
      epidemic size and disease transmissibility. Because of intense surveillance of
      travelers from infected countries, detection is more rapid and complete than on
      local surveillance. Travel information can provide a more reliable estimation of
      transmission parameters. METHOD: We developed an Approximate Bayesian Computation
      algorithm to estimate the basic reproduction number (R0) in addition to the
      reporting rate and unobserved epidemic start time, utilizing travel, and routine
      surveillance data in an influenza pandemic. A simulation was conducted to assess
      the sampling uncertainty. The estimation approach was further applied to the 2009
      influenza A/H1N1 pandemic in Mexico as a case study. RESULTS: In the simulations,
      we showed that the estimation approach was valid and reliable in different
      simulation settings. We also found estimates of R0 and the reporting rate to be
      1.37 (95% Credible Interval [CI]: 1.26-1.42) and 4.9% (95% CI: 0.1%-18%),
      respectively, in the 2009 influenza pandemic in Mexico, which were robust to
      variations in the fixed parameters. The estimated R0 was consistent with that in
      the literature. CONCLUSIONS: This method is useful for officials to obtain
      reliable estimates of disease transmissibility for strategic planning. We suggest
      that improvements to the flow of reporting for confirmed cases among patients
      arriving at different countries are required.

PMID- 29653204
TI  - EphA3 maintains radioresistance in head and neck cancers through epithelial
      mesenchymal transition.
AB  - Radiotherapy is a well-established therapeutic modality used in the treatment of
      many cancers. However, radioresistance remains a serious obstacle to successful
      treatment. Radioresistance can cause local recurrence and distant metastases in
      some patients after radiation treatment. Thus, many studies have attempted to
      identify effective radiosensitizers. Eph receptor functions contribute to tumor
      development, modulating cell-cell adhesion, invasion, neo-angiogenesis, tumor
      growth and metastasis. However, the role of EphA3 in radioresistance remains
      unclear. In the current study, we established a stable radioresistant head and
      neck cancer cell line (AMC HN3R cell line) and found that EphA3 was expressed
      predominantly in the radioresistant head and neck cancer cell line through DNA
      microarray, real time PCR and Western blotting. Additionally, we found that EphA3
      was overexpressed in recurrent laryngeal cancer specimens after radiation
      therapy. EphA3 mediated the tumor invasiveness and migration in radioresistant
      head and neck cancer cell lines and epithelial mesenchymal transition- related
      protein expression. Inhibition of EphA3 enhanced radiosensitivity in the AMC HN
      3R cell line in vitro and in vivo study. In conclusion, our results suggest that
      EphA3 is overexpressed in radioresistant head and neck cancer and plays a crucial
      role in the development of radioresistance in head and neck cancers by regulating
      the epithelial mesenchymal transition pathway.

PMID- 29653205
TI  - Varicella Zoster Virus Reactivation in Adult Survivors of Hematopoietic Cell
      Transplantation: How Do We Best Protect Our Patients?
AB  - Reactivation of varicella zoster virus (VZV) remains a significant public health
      burden for long-term survivors of hematopoietic cell transplantation. Delayed
      immune reconstitution after transplantation due to immunosuppression, post
      transplant therapies, poor engraftment, and graft-versus-host disease leave a
      large number of patients at risk for herpes zoster (shingles) and its highly
      morbid complications. Although prophylaxis with acyclovir or valacyclovir has
      reduced the incidence of VZV reactivation as long as prophylaxis is continued,
      the incidence of disease in the late post-transplant period or after stopping
      prophylaxis is greater in the hematopoietic cell transplantation population than
      the general public. Therefore, additional interventions beyond long-term use of
      prophylactic antivirals are required to suppress VZV. Vaccines to elicit VZV
      specific immunity represent one method to enhance prevention of VZV reactivation,
      but care must be taken with live vaccines. Inactivated vaccines have been
      developed and require well-designed studies to determine their safety and
      efficacy in this high-risk population. Here, we report the available evidence for
      established and newly developed vaccines for VZV and discuss our view on their
      role in protecting our transplant survivors against VZV reactivation.

PMID- 29653206
TI  - Late Effects Screening Guidelines after Hematopoietic Cell Transplantation (HCT)
      for Hemoglobinopathy: Consensus Statement from the Second Pediatric Blood and
      Marrow Transplant Consortium International Conference on Late Effects after
      Pediatric HCT.
AB  - Allogeneic hematopoietic cell transplantation (HCT) can halt organ damage and
      eliminate symptoms in hemoglobin disorders, including sickle cell disease (SCD)
      and thalassemia major. Managing the residual manifestations of pre-HCT disease
      complications and the long-term effects of HCT requires systematic monitoring,
      follow-up and intervention when indicated. Late complications vary with age and
      disease status at HCT and with transplant variables such as preparative regimen,
      donor source and compatibility, and immune reconstitution. An international
      consensus conference sponsored by the Pediatric Blood and Marrow Transplant
      Consortium in May 2016 entitled "Late Effects Screening and Recommendations
      Following HCT for Immune Deficiency and Nonmalignant Hematologic Disorders"
      focused on follow-up after HCT for hemoglobinopathy. An earlier publication from
      experts who participated in this session described the pathophysiology and
      spectrum of complications that HCT recipients experience after HCT for SCD and
      thalassemia major. This companion publication summarizes the consensus reached by
      this group of experts about long-term follow-up guidelines after HCT for
      hemoglobinopathy. In addition, these guidelines might also be included in studies
      of novel curative therapies such as autologous HCT after hematopoietic progenitor
      stem cell gene modification.

PMID- 29653207
TI  - Teaching a Young Dog New Tricks: Modifications to the Post-Transplantation
      Cyclophosphamide Haploidentical Transplantation Platform.

PMID- 29653208
TI  - Efficacy and safety of ixekizumab over 4 years of open-label treatment in a phase
      2 study in chronic plaque psoriasis.
AB  - BACKGROUND: Ixekizumab has demonstrated improvement in patients with moderate-to
      severe psoriasis by selectively targeting interleukin-17A, which is a
      proinflammatory cytokine that is important in the pathogenesis of psoriasis.
      OBJECTIVE: To report 4-year efficacy and safety results from the open-label
      extension (OLE) of this phase 2 trial. METHODS: Analysis was by last observation
      carried forward. Patients received ixekizumab, 120 mg, and then 80 mg
      subcutaneously once every 4 weeks. RESULTS: Of the patients who completed the
      randomized placebo-controlled trial, 93% entered the OLE. A 75% reduction in the
      Psoriasis Area Severity Index score was reported in 82% of patients at week 208
      of the OLE. A static Physician's Global Assessment score of 0 or 1 was reported
      in 64% of patients, and a score of 0 was reported in 45% at week 208. Patients'
      Dermatology Life Quality Index and Itch Visual Analog Scale scores decreased when
      compared with baseline. Improvements were observed in other efficacy and health
      outcome measures. Serious adverse events were observed in 16.7% of patients, and
      87% had 1 or more treatment-emergent adverse events. Three patients had serious
      infections. One patient reported 2 major cardiovascular events. LIMITATIONS: The
      study was unblinded and lacked a placebo or active comparator. CONCLUSIONS:
      Efficacy was shown to be maintained for up to 4 years of ixekizumab treatment.

PMID- 29653209
TI  - Diversity in dermatology: Roadmap for improvement.
AB  - The American Academy of Dermatology has taken an active stance in addressing the
      lack of racial and ethnic diversity in the specialty. At the American Academy of
      Dermatology President's Conference on Diversity in Dermatology, which was held on
      August 5, 2017, key action items to increase the number of practicing board
      certified dermatologists who are under-represented in medicine (UIM) were
      identified in 3 main areas. The action items include increasing the pipeline of
      UIM students applying to medical school, increasing UIM medical students'
      exposure to the field of dermatology and their level of interest in it, and
      increasing the number of UIM students recruited into dermatology residency
      programs.

PMID- 29653211
TI  - Dermoscopy is a useful bedside tool for the evaluation of cutaneous loxoscelism.

PMID- 29653210
TI  - Neutrophilic dermatoses: Pathogenesis, Sweet syndrome, neutrophilic eccrine
      hidradenitis, and Behcet disease.
AB  - Neutrophilic dermatoses are a heterogeneous group of inflammatory skin disorders
      that present with unique clinical features but are unified by the presence of a
      sterile, predominantly neutrophilic infiltrate on histopathology. The morphology
      of cutaneous lesions associated with these disorders is heterogeneous, which
      renders diagnosis challenging. Moreover, a thorough evaluation is required to
      exclude diseases that mimic these disorders and to diagnose potential associated
      infectious, inflammatory, and neoplastic processes. While some neutrophilic
      dermatoses may resolve spontaneously, most require treatment to achieve
      remission. Delays in diagnosis and treatment can lead to significant patient
      morbidity and even mortality. Therapeutic modalities range from systemic
      corticosteroids to novel biologic agents, and the treatment literature is rapidly
      expanding. The first article in this continuing medical education series explores
      the pathogenesis of neutrophilic dermatoses and reviews the epidemiology,
      clinical and histopathologic features, diagnosis, and management of Sweet
      syndrome, neutrophilic eccrine hidradenitis, and Behcet disease.

PMID- 29653212
TI  - Improving classification of melanocytic nevi: Association of BRAF V600E
      expression with distinct histomorphologic features.
AB  - BACKGROUND: A subset of melanomas carrying a B-Raf proto-oncogene,
      serine/threonine kinase gene (BRAF) V600E mutation, which is the most common
      targetable mutation in melanoma, arise in association with a melanocytic nevus
      that is also harboring a BRAF V600E mutation. The detailed histomorphologic
      characteristics of nevi positive for BRAF V600E have not been systematically
      documented. OBJECTIVE: To identify histomorphologic features correlating with
      BRAF V600E status in nevi. METHODS: We retrospectively identified melanocytic
      nevi from our laboratory reporting system. We performed a histomorphologic
      analysis and analysis of BRAF V600E expression by immunohistochemistry. RESULTS:
      Thirteen nevi (14.8%) were negative and 76 (86.4%) were positive for BRAF V600E.
      The nevi positive for BRAF V600E were predominantly dermal (predominantly dermal
      growth in 55.3% of nevi positive for BRAF V600E and 15.4% of nevi negative for
      BRAF V600E [P = .01]) and showed a congenital growth pattern (congenital growth
      pattern in 51.3% of nevi positive for BRAF V600E and 15.4% of nevi negative for
      BRAF V600E [P = .02]). Compared with nevi negative for BRAF V600E, those that
      were positive for BRAF V600E often exhibited predominantly nested intraepidermal
      melanocytes, larger junctional nests, abrupt lateral circumscription, and larger
      cell size. Architectural disorder and inflammatory infiltrates were seen more
      often in nevi negative for BRAF V600E. BRAF sequencing of a subset of nevi
      confirmed the immunohistochemical results. LIMITATIONS: Limitations include the
      study's retrospective design and the small sample size of nevi negative for BRAF
      V600E. CONCLUSIONS: BRAF V600E is associated with distinct histomorphologic
      features in nevi. These features may contribute to improving the accuracy of
      classification and diagnosis of melanocytic neoplasms.

PMID- 29653213
TI  - Neutrophilic dermatoses: Pyoderma gangrenosum and other bowel- and arthritis
      associated neutrophilic dermatoses.
AB  - Neutrophilic dermatoses are a heterogeneous group of inflammatory skin disorders
      that present with unique clinical features but are unified by the presence of a
      sterile, predominantly neutrophilic infiltrate on histopathology. The morphology
      of cutaneous lesions associated with these disorders is heterogeneous, which
      renders diagnosis challenging. Moreover, a thorough evaluation is required to
      exclude diseases that mimic these disorders and to diagnose potential associated
      infectious, inflammatory, and neoplastic processes. While some neutrophilic
      dermatoses may resolve spontaneously, most require treatment to achieve
      remission. Delays in diagnosis and treatment can lead to significant patient
      morbidity and even mortality. Therapeutic modalities range from systemic
      corticosteroids to novel biologic agents, and the treatment literature is rapidly
      expanding. The second article in this continuing medical education series reviews
      the epidemiology, clinical characteristics, histopathologic features, diagnosis,
      and management of pyoderma gangrenosum as well as bowel-associated dermatosis
      arthritis syndrome and the arthritis-associated neutrophilic dermatoses
      rheumatoid neutrophilic dermatitis and adult Still disease.

PMID- 29653214
TI  - Poly(propyleneimine) glycodendrimers non-covalently bind ATP in a pH- and salt
      dependent manner - model studies for adenosine analogue drug delivery.
AB  - Adenosine analogue drugs (such as fludarabine or cladribine) require transporter
      mediated uptake into cells and subsequent phosphorylation for anticancer
      activity. Therefore, application of nanocarrier systems for direct delivery of
      active triphosphate forms has been proposed. Here, we applied isothermal
      titration calorimetry and zeta potential titration to determine the stoichiometry
      and thermodynamic parameters of interactions between 4th generation
      poly(propyleneimine) dendrimers (unmodified or sugar-modified for increased
      biocompatibility) and ATP as a model adenosine nucleotide. We showed that
      glycodendrimers have the ability to efficiently interact with nucleoside
      triphosphates and to form stable complexes via electrostatic interactions between
      the ionized phosphate and amino groups on the nucleotide and the dendrimer,
      respectively. The complexation process is spontaneous, enthalpy-driven and
      depends on buffer composition (strongest interactions in organic buffer) and pH
      (more binding sites in acidic pH). These properties allow us to consider maltose
      modified dendrimers as especially promising carriers for adenosine analogues.

PMID- 29653215
TI  - The effect of mesoporous silica impregnation on tribo-electrification
      characteristics of flurbiprofen.
AB  - Tribo-electrification is a common occurrence within the pharmaceutical industry
      where solid dosage forms constitute majority of pharmaceutical formulations.
      Tribo-electrification of powders leads to a range of complications such as
      adhesion of particulate material to the processing equipment resulting in
      segregation, affecting the content uniformity. Flurbiprofen, a highly charging
      material, was used as a model drug to investigate the tribo-electrification and
      adhesion characteristics by impregnating the model drug inside a mesoporous
      silica matrix. The model drug was impregnated using i) solvent loading, and ii)
      physical mixing methods, at varying degree of silica to drug ratio (5-20% w/w).
      The resulting mixtures were tribo-charged using a custom built device based on a
      shaking concept inside a stainless steel capsule, consisting of a Faraday cup and
      connected to electrometer. The electrostatic charge and the percentage adhesion
      of Flurbiprofen were reduced in both drug loading methods. The solvent
      impregnation method using acetone was more successful at reducing the
      electrostatic charge build up on flurbiprofen than physical powder mixing. The
      percentage adhesion to the shaking capsule was reduced notably as a result of
      loading the drug in the SBA-15 porous network. The results illustrate that the
      incorporation of highly charged model drug inside a low-charging pharmaceutical
      carrier system to be an effective approach in control the induction of tribo
      electrification phenomena during powder processing.

PMID- 29653216
TI  - Molecular investigation of HIV-1 cross-group transmissions during an outbreak
      among people who inject drugs (2011-2014) in Athens, Greece.
AB  - New diagnoses of HIV-1 infection among people who inject drugs (PWID) rocketed in
      Athens, Greece between 2011 and 2014 (HIV-1 outbreak). Our aim was to identify,
      during that period, potential cross-group transmissions between the within-Greece
      PWID and other risk or national groups using molecular methods. Sequences from 33
      PWID were outside the PWID-outbreak networks in Greece (PWID-imported
      transmissions). Phylogenetic analyses on 28 of these sequences (subtypes A and B)
      showed that 11 subtype B infections originated from Greece, whereas 8 and 7
      subtype A strains were from former Soviet Union countries (AFSU) and Greece,
      respectively. The putative source in half of the PWID-imported transmissions with
      Greek origin was an individual who acquired HIV via sexual contact. During four
      years of an HIV-1 outbreak among PWID in Athens, Greece, 33 individuals in this
      group (4.6% of all diagnoses with phylogenetic analyses) are likely to represent
      infections, sexually or injection-acquired, outside the within-Greece-PWID
      outbreak networks. Combined molecular and traditional HIV surveillance to monitor
      introductions of new strains, and interventions that aim at reducing the rate of
      both injection and sexual risky practices are needed during drug injection
      related HIV outbreaks.

PMID- 29653217
TI  - Customizing poly(lactic-co-glycolic acid) particles for biomedical applications.
AB  - : Nano- and microparticles have increasingly widespread applications in
      nanomedicine, ranging from drug delivery to imaging. Poly(lactic-co-glycolic
      acid) (PLGA) particles are the most widely-applied type of particles due to their
      biocompatibility and biodegradability. Here, we discuss the preparation of PLGA
      particles, and various modifications to tailor particles for applications in
      biological systems. We highlight new preparation approaches, including
      microfluidics and PRINT method, and modifications of PLGA particles resulting in
      novel or responsive properties, such as Janus or upconversion particles. Finally,
      we describe how the preparation methods can- and should-be adapted to tailor the
      properties of particles for the desired biomedical application. Our aim is to
      enable researchers who work with PLGA particles to better appreciate the effects
      of the selected preparation procedure on the final properties of the particles
      and its biological implications. STATEMENT OF SIGNIFICANCE: Nanoparticles are
      increasingly important in the field of biomedicine. Particles made of polymers
      are in the spotlight, due to their biodegradability, biocompatibility,
      versatility. In this review, we aim to discuss the range of formulation
      techniques, manipulations, and applications of poly(lactic-co-glycolic acid)
      (PLGA) particles, to enable a researcher to effectively select or design the
      optimal particles for their application. We describe the various techniques of
      PLGA particle synthesis and their impact on possible applications. We focus on
      recent developments in the field of PLGA particles, and new synthesis techniques
      that have emerged over the past years. Overall, we show how the chemistry of PLGA
      particles can be adapted to solve pressing biological needs.

PMID- 29653218
TI  - Comparing Ran-Out Status of Inhaled Short-Acting Beta-Agonists in Emergency
      Department Patients with Acute Asthma: 1996-1998 versus 2015-2017.
AB  - BACKGROUND: Medication nonadherence, including running out of inhaled asthma
      medications, is an important problem. OBJECTIVE: The objective of this study was
      to examine the changes in the proportion of adults with acute asthma who ran out
      of their short-acting beta-agonist (SABA) inhalers before presenting to the
      emergency department (ED) between 1996--1998 and 2015-2017. METHODS: We analyzed
      data from prospective multicenter observational cohort studies of ED adult
      patients (aged 18-54 years) with acute asthma. Within the same 3 EDs, we
      performed a structured interview during 2 time periods: 1996-1998 and 2015-2017.
      We fitted multivariable models to compare ran-out status between the 2 periods,
      adjusting for the baseline patient demographics, socioeconomic status, chronic
      asthma factors, and health care utilization factors. We further adjusted for the
      presence of a written action plan-an intervenable factor. RESULTS: The analytic
      cohort comprised 353 patients (150 from the 1996-1998 studies and 203 from the
      2015-2017 study). Over the approximately 20-year period, the proportion of
      patients who ran out of SABA inhalers increased (18% in 1996-1998 vs 26% in 2015
      2017). In the multivariable model, compared with patients in 1996-1998, those in
      2015-2017 had a significantly higher risk of running out of their SABA inhalers
      (adjusted odds ratio [OR] 2.01; 95% confidence interval [CI] 1.06-3.81; P = .03).
      With further adjustment for the presence of a written action plan, this
      difference attenuated (adjusted OR 1.66; 95% CI 0.75-3.68; P = .21). CONCLUSIONS:
      Between 1996 and 2017, the proportion of ED patients with asthma who ran out of
      SABA inhalers significantly increased. The increase was explained, at least
      partially, by a lack of a written action plan.

PMID- 29653219
TI  - Anaphylaxis knowledge in camp personnel.

PMID- 29653220
TI  - Genetic analysis of Charcot-Marie-Tooth disease in Denmark and the implementation
      of a next generation sequencing platform.
AB  - Charcot-Marie-Tooth disease (CMT) is a heterogeneous group of hereditary
      polyneuropathies. Variants in more than 80 different genes have been associated
      with the disorder. In recent years, the introduction of next generation
      sequencing (NGS) techniques have completely changed the genetic diagnostic
      approach from the analysis of a handful of genes to the analysis of all genes
      associated with CMT in a single run. In this study we describe the CMT
      diagnostics in Denmark in 1992-2012, prior to the implementation of NGS, by
      combining laboratory- and national registry data. We investigate the effect of
      implementing a targeted NGS approach of 63 genes associated with CMT in the
      diagnostic laboratory setting. This was performed by analyzing a cohort of 195
      samples from patients previously analyzed by Sanger sequencing and quantitative
      analysis for the common causes of CMT without reaching a molecular diagnosis. A
      total of 1442 CMT analyses were performed in Denmark in the period 1992-2012; a
      disease-causing variant was detected in 21.6% of the cases. Interestingly, the
      diagnosis was genetically confirmed in significantly more women than men; 25.9%
      compared to18.5%. In our study cohort, we found a 5.6% increase in the diagnostic
      yield with the introduction of a targeted NGS approach.

PMID- 29653221
TI  - An atypical phenotype of a patient with infantile spinal muscular atrophy with
      respiratory distress type 1 (SMARD 1).
AB  - Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a rare
      autosomal recessive disease characterized by infancy-onset diaphragmatic palsy
      and symmetrical distal muscular weakness. SMARD1 is caused by loss-of-function
      mutations in IGHMBP2 gene. In this article, we report a male SMARD1 patient with
      two compound heterozygous mutations (NM_002180.2: c.688C > G; p.(Gln230Glu)) and
      (NM_002180.2: c.1737C > A; p.(Phe579Leu)), one of which (c.688C > G; ClinVar
      accession: SUB3344743: SCV000612189) is novel. He suffered from diaphragmatic
      palsy and distal muscular weakness from 6 months of age. His lower limbs were at
      first in hypertonia, and then gradually progressed into hypotonia. More
      interestingly, bronchoscopy has shown the diffuse tracheobronchomalacia, which
      had been reported only once in a SMARD1 patient who also had the same mutation
      (c.1737C > A) as our patient. We constructed the model of IGHMBP2 and mapped both
      mutations in the structure to analyze the structural impact of both mutations
      (c.688C > G and c.1737C > A) on the IGHMBP2 protein, which showed that mutation
      c.688C > G reduces greatly the stability of domain 1A of IGHMBP2, while the
      structural impact of c.1737C > A is not extensive.

PMID- 29653222
TI  - Gemcitabine loaded microbubbles for targeted chemo-sonodynamic therapy of
      pancreatic cancer.
AB  - Pancreatic cancer remains one of the most lethal forms of cancer with a 10-year
      survival of <1%. With little improvement in survival rates observed in the past
      40 years, there is a significant need for new treatments or more effective
      strategies to deliver existing treatments. The antimetabolite gemcitabine (Gem)
      is the most widely used form of chemotherapy for pancreatic cancer treatment, but
      is known to produce significant side effects when administered systemically. We
      have previously demonstrated the benefit of combined chemo-sonodynamic therapy
      (SDT), delivered using oxygen carrying microbubbles (O2MB), as a targeted
      treatment for pancreatic cancer in a murine model of the disease. In this
      manuscript, we report the preparation of a biotin functionalised Gem ligand for
      attachment to O2MBs (O2MB-Gem). We demonstrate the effectiveness of chemo
      sonodynamic therapy following ultrasound-targeted-microbubble-destruction (UTMD)
      of the O2MB-Gem and a Rose Bengal loaded O2MB (O2MB-RB) as a targeted treatment
      for pancreatic cancer. Specifically, UTMD using the O2MB-Gem and O2MB-RB
      conjugates reduced the viability of MIA PaCa-2, PANC-1, BxPC3 and T110299
      pancreatic cancer cells by >60% (p < 0.001) and provided significant tumour
      growth delay (>80%, p < 0.001) compared to untreated animals when human xenograft
      MIA PaCa-2 tumours were treated in SCID mice. The toxicity of the O2MB-Gem
      conjugate was also determined in healthy non-tumour bearing MF1 mice and revealed
      no evidence of renal or hepatic damage. Therefore, the results presented in this
      manuscript suggest that chemo-sonodynamic therapy using the O2MB-Gem and O2MB-RB
      conjugates, is potentially an effective targeted and safe treatment modality for
      pancreatic cancer.

PMID- 29653223
TI  - Acid-sensitive hybrid polymeric micelles containing a reversibly activatable cell
      penetrating peptide for tumor-specific cytoplasm targeting.
AB  - Cell-penetrating peptides (CPPs) have become a novel drug delivery system due to
      their distinct advantages, including high cell transmembrane potency and ability
      to carry cargo molecules inside cells. However, owing to their cationic charge
      and non-specificity characteristics, the clinical application of CPPs is limited.
      In the current study, we engineered a reversibly activatable cell-penetrating
      peptide (RACPP), containing oligoarginine fused to a pH-sensitive masking
      sequence via a polyglycine linker ((HE)10G5R6 or HE-CPP) with ultra-pH
      sensitivity. The HE-CPP sequence was coupled to the surface of polyethyleneglycol
      polylactic acid (PEG-PLA) polymer micelles (PMs-HE-CPP) to realize improve
      specificity and targeted delivery of encapsulated paclitaxel (PTX). PTX/PMs-HE
      CPP showed the satisfactory encapsulated efficiency, loading capacity, size
      distribution as well as reversible charge-conversion in response to the
      surrounding pH. The zeta potential of PMs-HE-CPP was negative at pH 7.5,
      moderately positive at pH 6.5, and even more positive at a lower pH. Coumarin 6
      loaded PMs-HE-CPP (C6/PMs-HE-CPP) showed enhanced tumor cellular uptake at a
      mildly acidic tumor microenvironment (pH 6.5) via energy-dependent and clathrin
      mediated endocytosis. Furthermore, PTX/PMs-HE-CPP had significantly higher
      cytotoxicity toward mice breast cancer (4T1) cells at pH 6.5 versus at pH 7.4. In
      vivo imaging studies in 4T1-BALB/c tumor xenograft models confirmed the tumor
      targeting characteristic of PMs-HE-CPP. PTX/PMs-HE-CPP also exhibited improved
      anti-tumor efficacy against unmodified polymer micelles and Taxol(r) in this
      tumor model. Accordingly, not only do RACPPs show the great potential to endow
      CPPs with specificity and reversible net-charge converting characteristic, they
      are also able to improve the targeting effect of nanoparticles.

PMID- 29653224
TI  - Tumor uptake of pegylated diabodies: Balancing systemic clearance and vascular
      transport.
AB  - The accumulation, dissemination and clearance of monoclonal antibody-based
      therapeutics or imaging reagents targeting tumor associated antigens is governed
      by several factors including affinity, size, charge, and valency. Tumor targeting
      antibody fragments have distinct advantages over intact monoclonal antibodies
      such as enhanced penetration within the tumor and rapid accumulation but are
      subject to rapid clearance. Polyethylene glycol (PEG)-modified antibody fragments
      can provide a way to balance tumor penetration and accumulation with improved
      serum persistence. In this study, we use a diabody, the dimeric antibody
      fragment, targeting the 5T4 antigen to assess the impact of PEGs of distinct size
      and shape on tumor accumulation and pharmacokinetics (PK). We show that PEG
      modified diabodies improved the PK of the parental diabody from a half-life of 40
      min to over 40 h for the higher molecular weight PEG conjugated diabodies. This
      improvement correlates with the increasing hydrodynamic size of pegylated
      diabodies, and can serve as a better predictor of the PK behavior of pegylated
      molecules than molecular weight alone. Tumor uptake profiles determined by
      quantitative PET imaging differed significantly based on PEG size and shape with
      diabody-PEG5K showing peak accumulation early on, but with the larger diabody
      PEG20K showing better sustained tumor uptake at later time points. In addition,
      we demonstrate that a diabody-PEG20K-B with a hydrodynamic radius (Rh) of 6 nm
      had superior tumor uptake than the larger diabody-PEG40K-B with Rh of 12 nm,
      indicating that beyond 6 nm, larger pegylated diabodies have a slower tumor
      uptake rate while having comparable clearance kinetics. Our data demonstrate that
      pegylated diabodies with Rh of ~6 nm have an optimal size and PK profile for
      tumor uptake. Understanding the impact of pegylation on PK and tumor uptake could
      facilitate the development of pegylated diabodies as therapeutics.

PMID- 29653225
TI  - Self-regulation of the Peruvian food industry: health message cues in the context
      of food and beverage advertisements.
AB  - OBJECTIVES: One strategy to prevent the onset of non-communicable diseases is to
      motivate healthy lifestyles through health media messages. In Peru, the food
      industry is currently implementing such strategy with health message cues, in the
      form of a small icon of a walking person or a healthy dish, appearing on
      televised food and beverage advertisements. Yet the extent of this practice is
      unknown. Thus, the objective of this study was three-fold: to identify (1) the
      food and beverage advertisements showing health cues, (2) the types of health
      cues, and (3) their length in time. STUDY DESIGN: Cross-sectional analysis of
      televised food and beverage advertisements that children and adolescents
      encounter on Peruvian television. METHODS: Content analysis of the presence of a
      health cue, type of health cue (physical activity and healthy diets), and the
      length in time of the health cue appearing on televised food and beverage
      advertisements in Peru. RESULTS: Health cues appeared on over 70% of
      advertisements for sugary drinks and tended to promote healthy diets more so than
      physical activity. CONCLUSIONS: This study shows that the food industry is
      currently advertising their products along with health message cues, and children
      and adolescents are exposed to this practice. Thus, we call for further testing
      of the effect of these health cues on children's and adolescents' food
      preferences and behaviors.

PMID- 29653226
TI  - Comparative and evolutionary analysis of the 14-3-3 family genes in eleven
      fishes.
AB  - 14-3-3 proteins are a type of highly conserved acidic proteins, which are
      distributed over a wide variety of organisms and are involved in multiple
      cellular processes. While the comparative and evolutionary analysis of this gene
      family is unavailable in various fish species. In this study, we identified 101
      putative 14-3-3 genes in 11 fish species and divided them into 5 groups via
      phylogenetic analysis. Synteny analysis implied conserved and dynamic evolution
      characteristics near the 14-3-3 gene loci in some vertebrates. We also found that
      some recombination events have accelerated the evolution of this gene family.
      Moreover, a positive selection site was also identified, and mutation of this
      site could reduce the 14-3-3 stability. Divergent expression profiles of the
      zebrafish 14-3-3 genes were further investigated under organophosphorus stress,
      suggesting that they may be involved in the different osmoregulation and immune
      response. The results will serve as a foundation for the further functional
      investigation into the 14-3-3 genes in fishes.

PMID- 29653227
TI  - RSRC1 and CPZ gene polymorphisms with neuroblastoma susceptibility in Chinese
      children.
AB  - Two new neuroblastoma susceptibility loci at 3q25 (RSRC1 rs6441201 G > A) and
      4p16 (CPZ rs3796725 T > C and rs3796727 A > G) were identified by a genome-wide
      association study (GWAS) involving Italians, African Americans and European
      Americans. In this case-control study with 393 neuroblastoma cases and 812
      controls, we investigated the association between these three polymorphisms and
      neuroblastoma susceptibility in Chinese population. We found that participants
      harboring the RSRC1 rs6441201A allele were associated with an increased risk of
      neuroblastoma (AA vs. GG: adjusted OR = 1.55, 95% CI = 1.03-2.34, P = 0.036). No
      significant association between the CPZ polymorphisms (rs3796725 T > C and
      rs3796727A > G) and neuroblastoma susceptibility was observed. In conclusion, our
      results confirm that the RSRC1 rs6441201A allele is associated with neuroblastoma
      susceptibility in Chinese population.

PMID- 29653228
TI  - Down-regulated let-7b-5p represses glycolysis metabolism by targeting AURKB in
      asthenozoospermia.
AB  - Glycolysis, through anaerobic respiration, can supply energy for human sperm
      motility. MicroRNAs (miRNAs) could participate in the glycolytic pathway through
      regulating target genes. To investigate the potential role of glycolysis-related
      miRNAs in asthenozoospermia, TaqMan Low Density Array (TLDA) was used to screen
      potentially functional miRNAs, and seven glycolysis-related miRNAs were isolated
      to be related to asthenozoospermia. After qRT-PCR validation, only one seminal
      plasma miRNA, let-7b-5p, was found significantly decreased in severe
      asthenozoospermia cases compared with healthy controls. To further understand
      whether let-7b-5p is involved in asthenozoospermia by regulating the glycolytic
      pathway, we carried out gain-and-loss function study of let-7b-5p in GC-2 cells
      and detected the glycolytic activities. Our results showed that knocking down let
      7b-5p could inhibit glycolytic activities. Besides, we also found overexpressed
      Aurkb (a target gene of let-7b-5p) could recapitulate the effects of knocking
      down let-7b-5p. Our findings indicated that low expression of let-7b-5p could
      repress glycolysis in asthenozoospermia by targeting AURKB.

PMID- 29653229
TI  - The splicing of tiny introns of Paramecium is controlled by MAGO.
AB  - The exon junction complex (EJC) is a key element of the splicing machinery. The
      EJC core is composed of eIF4A3, MAGO, Y14 and MLN51. Few accessory proteins, such
      as CWC22 or UPF3, bind transiently to the EJC. The EJC has been implicated in the
      control of the splicing of long introns. To ascertain whether the EJC controls
      the splicing of short introns, we used Paramecium tetraurelia as a model
      organism, since it has thousands of very tiny introns. To elucidate whether EJC
      affects intron splicing in P. tetraurelia, we searched for EJC protein-coding
      genes, and silenced those genes coding for eIF4A3, MAGO and CWC22. We found that
      P. tetraurelia likely assembles an active EJC with only three of the core
      proteins, since MLN51 is lacking. Silencing of eIF4A3 or CWC22 genes, but not
      that of MAGO, caused lethality. Silencing of the MAGO gene caused either an
      increase, decrease, or no change in intron retention levels of some intron
      containing mRNAs used as reporters. We suggest that a fine-tuning expression of
      EJC genes is required for steady intron removal in P. tetraurelia. Taking into
      consideration our results and those published by others, we conclude that the EJC
      controls splicing independently of the intron size.

PMID- 29653230
TI  - Regulatory network analysis of high expressed long non-coding RNA LINC00941 in
      gastric cancer.
AB  - Accumulating evidence suggests that the aberrant expression of long non-coding
      RNAs is closely related to the carcinogenesis and progression of gastric cancer
      (GC), which is a type of prevalent tumor with a high incidence and mortality
      rate. However, it is still a challenge to find reliable biomarkers and to
      understand their molecular mechanisms in GC. In this study, we first confirmed
      that LINC00941was up-regulated in GC tumor tissues compared with adjacent normal
      tissues by RT-PCR, and found that the expression level of LINC00941 was
      correlated with invasion depth, lymphatic metastasis, and the TNM stage of
      patients with GC. Furthermore, by performing enrichment analysis based on the co
      expression network and regulatory network, we found that LINC00941 was associated
      with cancer related biological processes such as cell cycle, cell communication,
      cell migration, cell division, as well as processes associated with the immune
      system. Our results suggested that LINC00941 may be a potential novel biomarker
      for therapeutic or diagnostic of GC.

PMID- 29653231
TI  - ECSM2, an endothelial specific VE-cadherin binding protein, has a tyrosine
      phosphorylation site essential to cell migration.
AB  - Endothelial cell-specific molecule 2 (ECSM2) is a transmembrane protein located
      in cell-cell junction of endothelial cells (EC). ECSM2 was determined to play an
      important role in vascular development, EC migration, apoptosis and
      proliferation, however, no functional domains were determined in intracellular
      and extracellular region of ECSM2. In current work, functional domains of ECSM2,
      the relationship of ECSM2 with other endothelial specific protein such as VE
      cadherin and the role of ECSM2 in neovascular diseases were determined. It was
      shown that the 54th amino acid residue of ECSM2 extracellular domain was a
      tyrosine phosphorylation site, whose mutation led to the loss of EGF-induced
      tyrosine phosphorylation and inhibition of cell migration. In primary human
      umbilical vein endothelial cells, ECSM2 bound with VE-cadherin and VEGF
      stimulation enhanced their binding. In hepatocellular carcinoma, ECSM2 expression
      was increased, as compared with para-cancerous tissue. This data firstly revealed
      the functional sites of ECSM2, the crosstalk between ECSM2 and other endothelial
      cell specific molecules, the expression of ECSM2 in tissues of angiogenesis
      diseases, thus providing understanding about ECSM2 in depth.

PMID- 29653232
TI  - GATA6 loss-of-function mutation contributes to congenital bicuspid aortic valve.
AB  - Congenital bicuspid aortic valve (BAV), the most common form of birth defect in
      humans, is associated with substantial morbidity and mortality. Increasing
      evidence demonstrates that genetic risk factors play a key role in the
      pathogenesis of BAV. However, BAV is a genetically heterogeneous disease and the
      genetic determinants underpinning BAV in an overwhelming majority of patients
      remain unknown. In the present study, the coding exons and flanking introns of
      the GATA6 gene, which encodes a zinc-finger transcription factor essential for
      the normal development of the aortic valves, were sequenced in 152 unrelated
      patients with congenital BAV. The available relatives of a proband harboring an
      identified GATA6 mutation and 200 unrelated, ethnically matched healthy
      individuals used as controls were also genotyped for GATA6. The functional
      characteristics of the mutation were analyzed by using a dual-luciferase reporter
      assay system. As a result, a novel heterozygous GATA6 mutation, p.E386X, was
      identified in a family with BAV transmitted in an autosomal dominant mode. The
      nonsense mutation was absent in 400 control chromosomes. Biological assays
      revealed that the mutant GATA6 protein had no transcriptional activity compared
      with its wild-type counterpart. Furthermore, the mutation disrupted the
      synergistic transcriptional activation between GATA6 and GATA4, another
      transcription factor causally linked to BAV. In conclusion, this study firstly
      associates GATA6 loss-of-function mutation with enhanced susceptibility to
      familial BAV, which provides novel insight into the molecular mechanism of BAV,
      implying potential implications for genetic counseling and personalized
      management of BAV patients.

PMID- 29653234
TI  - Mepolizumab use: Post-approval academic practice experience.

PMID- 29653233
TI  - Three novel variants (p.Glu178Lys, p.Val245Met, p.Ser250Phe) of the phenylalanine
      hydroxylase (PAH) gene impair protein expression and function in vitro.
AB  - Phenylketonuria (PKU) is the most common inherited metabolic disease, an
      autosomal recessive disorder affecting >10,000 newborns each year globally. It
      can be caused by over 1000 different naturally occurring mutations in the
      phenylalanine hydroxylase (PAH) gene. We analyzed three novel naturally occurring
      PAH gene variants: p.Glu178Lys (c.532G>A), p.Val245Met (c.733G>A) and p.Ser250Phe
      (c.749C>T). The mutant effect on the PAH enzyme structure and function was
      predicted by bioinformatics software. Vectors expressing the corresponding PAH
      variants were generated for expression in E. coli and in HEK293T cells. The RNA
      expression of the three PAH variants was measured by quantitative reverse
      transcription polymerase chain reaction (RT-qPCR). The mutant PAH protein levels
      were determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS
      PAGE), western blot and enzyme-linked immunosorbent assay (ELISA). All three
      variants were predicted to be pathogenic by bioinformatics analysis. The
      transcription of the three PAH variants was similar to the wild type PAH gene in
      HEK293T cells. In contrast, the levels of mutant PAH proteins decreased
      significantly compared to the wild type control, in both E. coli and HEK293T
      cells. Our results indicate that the three novel PAH gene variants (p.Glu178Lys,
      p.Val245Met, p.Ser250Phe) impair PAH protein expression and function in
      prokaryotic and eukaryotic cells.

PMID- 29653235
TI  - Factors correlated with repeated aspirin dosing during aspirin desensitization.
AB  - BACKGROUND: Aspirin desensitization is an appropriate procedure for many patients
      with aspirin-exacerbated respiratory disease (AERD). Patients can require aspirin
      re-dosing, which prolongs the desensitization process. The frequency of this is
      not widely reported, nor is it known which patients will require multiple re
      dosing. OBJECTIVE: To determine the frequency of and factors associated with
      repeat aspirin re-dosing during desensitization. METHODS: Charts of aspirin
      desensitization procedures from 2011 to 2016 at the University of Michigan
      Allergy/Immunology Clinic were reviewed. Reactions with provoking doses and
      number of dose repetitions were characterized. Previous AERD history, medical
      history, medications, and baseline spirometry were also recorded. Bivariate
      correlation and multivariate logistic regression were used to analyze
      associations between patient characteristics and need for repeated dosing of
      aspirin. RESULTS: A total of 84 positive-reacting patients during desensitization
      were identified. Of these patients, 33% required 2 or more aspirin dose
      repetitions during desensitization. Requiring 2 or more repeat doses during
      desensitization was associated with male gender (odds ratio = 6.194, P = .008),
      forced expiratory volume in 1 second (FEV1) decrease during desensitization (odds
      ratio = 1.075 per percent point drop, P = .021), and initial aspirin provoking
      dose during desensitization of 81 mg or lower (odds ratio = 11.111, P = .003). No
      association was found with pre-desensitization medications, asthma severity, AERD
      duration, or number/character of reported previous aspirin reactions. CONCLUSION:
      During aspirin desensitization for AERD, approximately one third of our patients
      require multiple repeat doses. Risk factors for multiple repeated doses include
      male gender, drop in FEV1, and lower aspirin provoking doses during
      desensitization. This information can help inform which patients may require
      multiple re-dosing for desensitization.

PMID- 29653236
TI  - Chromosome 1q23.3q31.1 deletion associated with decreased newborn screening of T
      cell receptor rearrangement circles (TRECs).

PMID- 29653237
TI  - Oral corticosteroids should be available on-hand at home for the next asthma
      exacerbation!

PMID- 29653238
TI  - The pediatric asthma yardstick: Practical recommendations for a sustained step-up
      in asthma therapy for children with inadequately controlled asthma.
AB  - Current asthma guidelines recommend a control-based approach to management
      involving assessment of impairment and risk followed by implementation of
      treatment strategies individualized according to the patient's needs and
      preferences. However, for children with asthma, achieving control can be elusive.
      Although tools are available to help children (and families) track and manage day
      to-day symptoms, when and how to implement a longer-term step-up in care is less
      clear. Furthermore, treatment is challenged by the 3 age groups of childhood
      adolescence (12-18 years old), school age (6-11 years old), and young children
      (<=5 years old)-and what works for 1 age group might not be the best approach for
      another. The Pediatric Asthma Yardstick provides an in-depth assessment of when
      and how to step-up therapy for the child with not well or poorly controlled
      asthma. Development of this tool follows others in the Yardstick series,
      presenting patient profiles and step-up strategies based on current guidance
      documents, but modified according to newer data and the authors' combined
      clinical experience. The objective is to provide clinicians who treat children
      with asthma practical and clinically relevant recommendations for each step-up
      and each intervention, with the intent of helping practitioners better treat
      their pediatric patients with asthma, particularly those who do not always
      respond to recommended therapies.

PMID- 29653239
TI  - Comments on "vascularised fibula or induced membrane to treat congenital
      pseudarthrosis of the tibia: A multicentre study of 18 patients with a mean 9.5
      year follow-up" of F. Vigouroux, G. Mezzadri, R. Parot, A. Gazarian, S. Pannier,
      F. Chotel. Published in Orthop Traumatol Surg Res. 2017 Sep;103:747-753.

PMID- 29653240
TI  - Medial meniscus posterior root tear induces pathological posterior extrusion of
      the meniscus in the knee-flexed position: An open magnetic resonance imaging
      analysis.
AB  - BACKGROUND: A medial meniscus posterior root tear (MMPRT) is defined as an injury
      to the posterior meniscal insertion on the tibia. In MMPRT, the medial meniscus
      (MM) hoop function is damaged, and the MM undergoes a medial extrusion into the
      interior from the superior articular surface of the tibia. However, the details
      of MM position and movement during knee joint movement are unclear in MMPRT
      cases. The present study aims to evaluate MM position and movement via magnetic
      resonance imaging (MRI) examination of the MM posterior extrusion (MMPE) at knee
      flexion angles of 10 degrees  and 90 degrees . We hypothesized that, during knee
      flexion, the MM will shift to the posterior and the posterior extrusion will
      increase compared to that when the knee is extended. MATERIALS AND METHODS:
      Twenty-four patients were diagnosed with symptomatic MMPRT on open MRI
      examination. Preoperative MMPE, anteroposterior interval (API) of the MM, and MM
      medial extrusion (MMME) at knee flexion angles of 10 degrees  and 90 degrees 
      were measured. RESULTS: For patients with MMPRT, the MMPE increased from -4.77+/
      1.43mm to 3.79+/-1.17mm (p<0.001) when the knee flexion angle increased from 10
      degrees  to 90 degrees . Further, flexing the knee from 10 degrees  to 90 degrees
      decreased the API of the MM from 20.19+/-4.22mm to 16.41+/-5.14mm (p<0.001).
      MMME showed no significant change between knee flexion angles of 10 degrees  and
      90 degrees . DISCUSSION: This study demonstrated that, in cases of MMPRT, the
      MMPE clearly increases when the knee is flexed to 90 degrees , while MMME does
      not change. Our results suggest that open MRI examination can be used to evaluate
      the dynamic position of the posterior MM by scanning the knee as it flexes to 90
      degrees . LEVEL OF EVIDENCE: IV: retrospective cohort study.

PMID- 29653241
TI  - Navigation for lower limb alignment during internal fixation of complex tibial
      plateau fractures.
AB  - In complex fractures of the proximal tibial metaphysis and epiphysis, possible
      adverse outcomes after internal fixation include not only joint surface
      incongruity, but also lower limb malalignment requiring revision surgery.
      Navigation has been proven effective for the intraoperative control of lower limb
      alignment during osteotomy and knee arthroplasty. In complex traumatic fractures,
      temporary fixation by a locking screw plate allows sensor positioning followed by
      navigation maneuvers to adjust lower limb alignment. If malalignment is found,
      the construct can be modified economically by altering the diaphyseal fixation
      without modifying the metaphyseal screws. The objective of this study was to
      describe the use of navigation in three patients who required internal fixation
      of tibial-plateau fractures.

PMID- 29653242
TI  - Effect of combined flexion and external rotation on measurements of the proximal
      femur from anteroposterior pelvic radiographs.
AB  - INTRODUCTION: Fixed flexion and external rotation contractures are common in
      patients with hip osteoarthritis and, in particular, before total hip replacement
      (THR). We aimed to answer the following question: how does combined flexion and
      external rotation of the femur influence the radiographic assessment of (1)
      femoral offset (FO) (2) neck-shaft angle (NSA) and (3) distance (parallel to the
      femoral axis) from greater trochanter to femoral head center (GT-FHC)?
      HYPOTHESIS: Combined flexion and external rotation impact the accuracy of two
      dimensional (2D) proximal femur measurements. MATERIALS AND METHODS: Three
      dimensional (3D) CT segmentations of the right femur from 30 male and 42 female
      subjects were acquired and used to build a statistical shape model. A cohort
      (n=100; M:F=50:50) of shapes was generated using the model. Each 3D femur was
      subjected to external rotation (0 degrees -50 degrees ) followed by flexion (0
      degrees -50 degrees ) in 10 degrees  increments. Simulated radiographs of each
      femur in these orientations were produced. Measurements of FO, NSA and GT-FHC
      were automatically taken on the 2D images. RESULTS: Combined rotations influenced
      the measurement of FO (p<0.05), NSA (p<0.001), and GT-FHC (p<0.001). Femoral
      offset was affected predominantly by external rotation (19.8+/-2.6mm [12.2 to
      26.1mm] underestimated at 50 degrees ); added flexion in combined rotations only
      slightly impacted measurement error (20.7+/-3.1mm [13.2 to 28.8mm] underestimated
      at 50 degrees  combined). Neck-shaft angle was reduced with flexion when external
      rotation was low (9.5+/-2.1 degrees  [4.4 to 14.2 degrees ] underestimated at 0
      degrees  external and 50 degrees  flexion) and increased with flexion when
      external rotation was high (24.4+/-3.9 degrees  [15.7 to 31.9 degrees ]
      overestimated at 50 degrees  external and 50 degrees  flexion). Femoral head
      center was above GT by 17.0+/-3.4mm [3.9 to 22.1mm] at 50 degrees  external and
      50 degrees  flexion. In contrast, in neutral rotation, FHC was 12.2+/-3.4mm [3.9
      to 22.1mm] below GT. DISCUSSION: This investigation adds to current understanding
      of the effect of femoral orientation on preoperative planning measurements
      through the study of combined rotations (as opposed to single-axis). Planning
      measurements are shown to be significantly affected by flexion, external
      rotation, and their interaction. LEVEL OF EVIDENCE: IV Biomechanical study.

PMID- 29653243
TI  - What's new in periprosthetic joint infection: Diagnosis and bacteria.

PMID- 29653244
TI  - Opioid use following cervical spine surgery: trends and factors associated with
      long-term use.
AB  - BACKGROUND CONTEXT: Limited or no data exist evaluating risk factors associated
      with prolonged opioid use following cervical arthrodesis. PURPOSE: The objectives
      of this study were to assess trends in postoperative narcotic use among
      preoperative opioid users (OUs) versus non-opioid users (NOUs) and to identify
      factors associated with postoperative narcotic use at 1 year following cervical
      arthrodesis. STUDY DESIGN/SETTING: This is a retrospective observational study.
      PATIENT SAMPLE: The patient sample included 17,391 patients (OU: 52.4%)
      registered in the Humana Inc claims dataset who underwent anterior cervical
      fusion (ACF) or posterior cervical fusion (PCF) between 2007 and 2015. OUTCOME
      MEASURES: Prolonged opioid usage was defined as narcotic prescription filling at
      1 year following cervical arthrodesis. METHODS: Based on preoperative opioid use,
      patients were identified as an OU (history of narcotic prescription filled within
      3 months before surgery) or a NOU (no preoperative prescription). Rates of opioid
      use were evaluated preoperatively for OU and trended for 1 year postoperatively
      for both OU and NOU. Multivariable regression techniques investigated factors
      associated with the use of narcotics at 1 year following ACF and PCF. Based on
      the model findings, a web-based interactive app was developed to estimate 1-year
      postoperative risk of using narcotics following cervical arthrodesis
      (http://neuro-risk.com/opiod-use/ or
      https://www.neurosurgerycost.com/opioid/opioid_use). RESULTS: Overall, 87.4% of
      the patients (n=15,204) underwent ACF, whereas 12.6% (n=2187) underwent PCF. At 1
      month following surgery, 47.7% of NOUs and 82% of OUs had a filled opioid
      prescription. Rates of prescription opioids declined significantly to 7.8% in
      NOUs versus 50.5% in OUs at 3 months, but plateaued at the 6- to 12-month
      postoperative period (NOU: 5.7%-6.7%, OU: 44.9%-46.9%). At 1 year, significantly
      higher narcotic prescription filling rates were observed in OUs compared with
      NOUs (45.3% vs. 6.3%, p<.001). Preoperative opioid use was a significant driver
      of 1-year narcotic use following ACF (odds ratio [OR]: 7.02, p<.001) and PCF (OR:
      6.98, p<.001), along with younger age (<=50 years), history of drug dependence,
      and lower back pain. CONCLUSIONS: Over 50% of the patients used opioids before
      cervical arthrodesis. Postoperative opioid use fell dramatically during the first
      3 months in NOU, but nearly half of the preoperative OUs will remain on narcotics
      at 1 year postoperatively. Our findings serve as a baseline in identifying
      patients at risk of chronic use and encourage discontinuation of opioids before
      cervical spine surgery.

PMID- 29653245
TI  - Improved clinical documentation leads to superior reportable outcomes: An
      accurate representation of patient's clinical status.
AB  - INTRODUCTION: Clinical documentation can be an underappreciated. Trauma Centers
      (TCs) are now routinely evaluated for quality performance. TCs with poor
      documentation may not accurately reflect actual injury burden or comorbidities
      and can impact accuracy of mortality measures. Markers exist to adjust crude
      death rates for injury severity: observed over expected deaths (O/E) adjust for
      injury; Case Mix Index (CMI) reflects disease burden, and Severity of Illness
      (SOI) measures organ dysfunction. We aim to evaluate the impact of implementing a
      Clinical Documentation Improvement Program (CDIP) on reported outcomes. METHODS:
      Review of 2-years of prospectively collected data for trauma patients, during the
      implementation of CDIP. A two-group prospective observational study design was
      used to evaluate the pre-implementation and the post-implementation phase of
      improved clinical documentation. T-test and Chi-Squared were used with
      significance defined as p < 0.05. RESULTS: In the pre-implementation period,
      there were 49 deaths out of 1419 (3.45%), while post-implementation period, had
      38 deaths out of 1454 (2.61%), (non-significant). There was however, a
      significant difference between O/E ratios. In the pre-phase, the O/E was 1.36 and
      0.70 in the post-phase (p < 0.001). The two groups also differed on CMI with a
      pre-group mean of 2.48 and a post-group of 2.87 (p < 0.001), indicating higher
      injury burden in the post-group. SOI started at 2.12 and significantly increased
      to 2.91, signifying more organ system dysfunction (p < 0.018). CONCLUSION:
      Improved clinical documentation results in improved accuracy of measures of
      mortality, injury severity, and comorbidities and a more accurate reflection in
      O/E mortality ratios, CMI, and SOI.

PMID- 29653246
TI  - Duodenal fistula: The most lethal surgical complication in a case series of
      radical gastrectomy.
AB  - BACKGROUND: Despite all advances regarding the surgical treatment of gastric
      cancer (GC), duodenal stump fistula (DF) continues to negatively affect
      postoperative outcomes. This study aimed to assess DF regarding its incidence,
      risk factors, management and impact on overall survival. METHODS: We
      retrospectively analyzed 562 consecutive patients who underwent gastrectomy for
      GC between 2009 and 2017. Clinicopathological characteristics analysis was
      performed comparing DF, other surgical fistulas and patients with uneventful
      postoperative course. RESULTS: DF occurred in 15 (2.7%) cases, and 51 (9%)
      patients had other surgical fistulas. Tumor located in the lower third of the
      stomach (p = 0.021) and subtotal gastrectomy (p = 0.002) were associated with
      occurrence of DF. The overall mortality rate was 40% for DF and 15.7% for others
      surgical fistulas (p = 0.043). The median time of DF onset was on postoperative
      day 9 (range 1-75). Conservative approach was performed in 8 patients and
      surgical intervention in 7 cases. Age (OR 7.41, p = 0.012) and DF (OR 9.06,
      p=0.020) were found to be independent risk factors for surgical mortality.
      Furthermore, patients without fistula had better long-term survival outcomes
      comparing to patients with any type of fistulas (p = 0.006). CONCLUSION: DF is
      related with distal tumors and patients submitted to subtotal gastrectomy. It
      affects not only the postoperative period with high morbidity and mortality
      rates, but may also have a negative impact on long-term survival.

PMID- 29653247
TI  - Somatosensory changes at forearm donor sites following three different surgical
      flap techniques.
AB  - BACKGROUND: The aim of this study was to investigate the somatosensory changes at
      the forearm donor region after using different types of modified flap surgical
      techniques. METHODS: Thirty-one patients, who underwent oral and maxillofacial
      reconstructive surgery involving the use of a traditional radial forearm flap
      (TRFF) or two modified radial forearm flap techniques (MRFF-I; MRFF-II),
      participated in the study. Cold detection threshold (CDT), warm detection
      threshold (WDT), cold pain threshold (CPT), heat pain threshold (HPT), pressure
      pain threshold (PPT), mechanical detection threshold (MDT), and mechanical pain
      threshold (MPT) were assessed at four sites of the forearms corresponding to the
      middle of the vascular pedicle (VP) area, the middle of the forearm flap area,
      and the corresponding contralateral sites (cVP and cFF) at about 5.0 +/- 1.9
      months after the surgery. Data were analysed with one-way ANOVA, and post-hoc
      tests were performed using Tukey's Honest Significant Difference test. RESULTS:
      Significant differences between the VP and cVP sites were detected for WDT (P <
      0.001) in TRFF and for WDT (P < 0.001) and MDT (P = 0.006) in MRFF-I. Significant
      differences among TRFF, MRFF-I, and MRFF-II at the VP site were detected for CDT
      (P = 0.022), WDT (P < 0.001), and MDT (P = 0.015). MRFF-II was associated with
      significantly higher sensitivity compared to that of TRFF for WDT (P = 0.017) and
      higher sensitivity compared to that of MRFF-I for CDT (P = 0.017), WDT (P <
      0.001), and MDT (P = 0.013). CONCLUSIONS: Significant sensory loss was detected
      for all types of surgical procedures with free forearm flaps. However, the MRFF
      II was associated with a better sensory recovery at short follow-up after
      surgery. These results suggest that a longer follow-up period and larger sample
      size should be included in future studies.

PMID- 29653248
TI  - Core trainee boot camp, a method for improving technical and non-technical skills
      of novice surgical trainees. A before and after study.
AB  - INTRODUCTION: The transition to surgical training can be a stressful time for
      trainees and is most evident during national handover periods where new graduates
      start and senior trainees rotate to new programmes. During this time, patient
      mortality can increase and Hospital efficiency reduces. This influence is
      compounded by the impact of working time directives. Intensive, simulation rich
      training programmes or "Boot Camps" have been postulated as a solution. This
      article highlights the development of a surgical boot camp for novice surgical
      trainees and the impact this can have on training. METHOD: A novel surgical boot
      camp was developed for all trainees within a surgical training region including
      nine acute NHS trusts. Participating cohort of trainees completed pre and post
      course questionnaires to assess technical and non-technical skills. RESULTS: 25
      trainees attended and completed the pre and post boot camp questionnaire.
      Significant improvements were seen with technical skills (p = 0.0429), overall
      non-technical skills (p < 0.001) including leadership (p = 0.022), communication
      (p = 0.010), situational awareness (p = 0.022), patient handover (p = 0.003),
      ward round skills (p = 0.005) and outpatient skill (p = 0.002). Trainees reported
      significantly increased ability to assess and manage a critically unwell patient
      (p = 0.001) and a trauma patient (p = 0.001). 96% of trainees have utilised the
      skills they learnt on Boot Camp and all trainees would recommend it as an
      induction programme. CONCLUSION: Surgical Boot Camps offer a timely chance to
      develop technical and non-technical skills whilst enhancing a trainee's
      confidence and knowledge and reduce the patient safety impact of the handover
      period.

PMID- 29653249
TI  - Directing neuronal cell fate in vitro: Achievements and challenges.
AB  - Human pluripotent stem cell (PSC) technology and direct somatic cell
      reprogramming have opened up a promising new avenue in the field of neuroscience.
      These recent advances allow researchers to obtain virtually any cell type found
      in the human brain, making it possible to produce and study functional neurons in
      laboratory conditions for both scientific and medical purposes. Although distinct
      approaches have shown to be successful in directing neuronal cell fate in vitro,
      their refinement and optimization, as well as the search for alternative
      approaches, remains necessary to help realize the full potential of the
      eventually derived neuronal populations. Furthermore, we are currently limited in
      the number of neuronal subtypes whose induction is fully established, and
      different cultivation protocols for each subtype exist, making it challenging to
      increase the reproducibility and decrease the variances that are observed between
      different protocols. In this review, we summarize the progress that has been made
      in generating various neuronal subtypes from PSCs and somatic cells, with special
      emphasis on chemically defined systems, transcription factor-mediated
      reprogramming and epigenetic-based approaches. We also discuss the efforts that
      are being made to increase the efficiency of current protocols and address the
      potential for the use of these cells in disease modelling, drug discovery and
      regenerative medicine.

PMID- 29653251
TI  - Probabilistic guidance for catheter tip motion in cardiac ablation procedures.
AB  - Radiofrequency catheter ablation is one of the commonly available therapeutic
      methods for patients suffering from cardiac arrhythmias. The prerequisite of
      successful ablation is sufficient energy delivery at the target site. However,
      cardiac and respiratory motion, coupled with endocardial irregularities, can
      cause catheter drift and dispersion of the radiofrequency energy, thus prolonging
      procedure time, damaging adjacent tissue, and leading to electrical reconnection
      of temporarily ablated regions. Therefore, positional accuracy and stability of
      the catheter tip during energy delivery is of great importance for the outcome of
      the procedure. This paper presents an analytical scheme for assessing catheter
      tip stability, whereby a sequence of catheter tip motion recorded at sparse
      locations on the endocardium is decomposed. The spatial sliding component along
      the endocardial wall is extracted from the recording and maximal slippage and its
      associated probability are computed at each mapping point. Finally, a global map
      is generated, allowing the assessment of potential areas that are compromised by
      tip slippage. The proposed framework was applied to 40 retrospective studies of
      congenital heart disease patients and further validated on phantom data and
      simulations. The results show a good correlation with other intraoperative
      factors, such as catheter tip contact force amplitude and orientation, and with
      clinically documented anatomical areas of high catheter tip instability.

PMID- 29653252
TI  - Inactivation of ceramide synthase 2 catalytic activity in mice affects
      transcription of genes involved in lipid metabolism and cell division.
AB  - The replacement of two consecutive histidine residues by alanine residues in the
      catalytic center of ceramide synthase 2 in a new transgenic mouse mutant (CerS2
      H/A) leads to inactivation of catalytic activity and reduces protein level to 60%
      of the WT level. We show here by qRT-PCR and transcriptome analyses that several
      transcripts of genes involved in lipid metabolism and cell division are
      differentially regulated in livers of CerS2 H/A mice. Thus, very long chain
      ceramides produced by CerS2 are required for transcriptional regulation of target
      genes. The hepatocellular carcinomata previously described in old CerS2 KO mice
      were already present in 8-week-old CerS2 H/A animals and thus are caused by the
      loss of CerS2 catalytic activity already during early life.

PMID- 29653254
TI  - Interactions between risk factors in the prediction of onset of eating disorders:
      Exploratory hypothesis generating analyses.
AB  - OBJECTIVE: Because no study has tested for interactions between risk factors in
      the prediction of future onset of each eating disorder, this exploratory study
      addressed this lacuna to generate hypotheses to be tested in future confirmatory
      studies. METHOD: Data from three prevention trials that targeted young women at
      high risk for eating disorders due to body dissatisfaction (N = 1271; M age 18.5,
      SD 4.2) and collected diagnostic interview data over 3-year follow-up were
      combined to permit sufficient power to predict onset of anorexia nervosa (AN),
      bulimia nervosa (BN), binge eating disorder (BED), and purging disorder (PD)
      using classification tree analyses, an analytic technique uniquely suited to
      detecting interactions. RESULTS: Low BMI was the most potent predictor of AN
      onset, and body dissatisfaction amplified this relation. Overeating was the most
      potent predictor of BN onset, and positive expectancies for thinness and body
      dissatisfaction amplified this relation. Body dissatisfaction was the most potent
      predictor of BED onset, and overeating, low dieting, and thin-ideal
      internalization amplified this relation. Dieting was the most potent predictor of
      PD onset, and negative affect and positive expectancies for thinness amplified
      this relation. CONCLUSIONS: Results provided evidence of amplifying interactions
      between risk factors suggestive of cumulative risk processes that were distinct
      for each disorder; future confirmatory studies should test the interactive
      hypotheses generated by these analyses. If hypotheses are confirmed, results may
      allow interventionists to target ultra high-risk subpopulations with more
      intensive prevention programs that are uniquely tailored for each eating
      disorder, potentially improving the yield of prevention efforts.

PMID- 29653253
TI  - Cholesterol and bile acid-mediated regulation of autophagy in fatty liver
      diseases and atherosclerosis.
AB  - Liver is the major organ that regulates whole body cholesterol metabolism.
      Disrupted hepatic cholesterol homeostasis contributes to the pathogenesis of
      nonalcoholic steatohepatitis, dyslipidemia, atherosclerosis, and cardiovascular
      diseases. Hepatic bile acid synthesis is the major catabolic mechanism for
      cholesterol elimination from the body. Furthermore, bile acids are signaling
      molecules that regulate liver metabolism and inflammation. Autophagy is a highly
      conserved lysosomal degradation mechanism, which plays an essential role in
      maintaining cellular integrity and energy homeostasis. In this review, we discuss
      emerging evidence linking hepatic cholesterol and bile acid metabolism to
      cellular autophagy activity in hepatocytes and macrophages, and how these
      interactions may be implicated in the pathogenesis and treatment of fatty liver
      disease and atherosclerosis.

PMID- 29653255
TI  - Promoting Father Involvement for Child and Family Health.
AB  - Paternal involvement in children's lives is associated with a variety of child
      outcomes, including improved cognition, improved mental health, reduced obesity
      rates, and asthma exacerbation. Given this evidence, the American Academy of
      Pediatrics has promoted actions by pediatricians to engage fathers in pediatric
      care. Despite these recommendations, the mother-child dyad, rather than the
      mother-father-child triad, remains a frequent focus of care. Furthermore,
      pediatric care is often leveraged to improve maternal health, such as screening
      for maternal depression, but paternal health is infrequently addressed even as
      men tend to exhibit riskier behaviors, poorer primary care utilization, and lower
      life expectancy. Therefore, increasing efforts by pediatric clinicians to engage
      fathers may affect the health of both father and child. These efforts to engage
      fathers are informed by currently used definitions and measures of father
      involvement, which are discussed here. Factors described in the literature that
      affect father involvement are also summarized, including culture and context;
      interpersonal factors; logistics; knowledge and self-efficacy; and attitudes,
      beliefs, and incentives. Innovative ways to reach fathers both in the clinic and
      in other settings are currently under investigation, including use of behavior
      change models, motivational interviewing, mobile technologies, peer support
      groups, and policy advocacy efforts. These modalities show promise in effectively
      engaging fathers and improving family health.

PMID- 29653250
TI  - Pluripotent stem cell-based therapy for Parkinson's disease: Current status and
      future prospects.
AB  - Parkinson's disease (PD) is one of the most common neurodegenerative disorders,
      which affects about 0.3% of the general population. As the population in the
      developed world ages, this creates an escalating burden on society both in
      economic terms and in quality of life for these patients and for the families
      that support them. Although currently available pharmacological or surgical
      treatments may significantly improve the quality of life of many patients with
      PD, these are symptomatic treatments that do not slow or stop the progressive
      course of the disease. Because motor impairments in PD largely result from loss
      of midbrain dopamine neurons in the substantia nigra pars compacta, PD has long
      been considered to be one of the most promising target diseases for cell-based
      therapy. Indeed, numerous clinical and preclinical studies using fetal cell
      transplantation have provided proof of concept that cell replacement therapy may
      be a viable therapeutic approach for PD. However, the use of human fetal cells as
      a standardized therapeutic regimen has been fraught with fundamental ethical,
      practical, and clinical issues, prompting scientists to explore alternative cell
      sources. Based on groundbreaking establishments of human embryonic stem cells and
      induced pluripotent stem cells, these human pluripotent stem cells have been the
      subject of extensive research, leading to tremendous advancement in our
      understanding of these novel classes of stem cells and promising great potential
      for regenerative medicine. In this review, we discuss the prospects and
      challenges of human pluripotent stem cell-based cell therapy for PD.

PMID- 29653257
TI  - beta-adrenergic receptors reduce the threshold for induction and stabilization of
      LTP and enhance its magnitude via multiple mechanisms in the ventral but not the
      dorsal hippocampus.
AB  - The hippocampus is a functionally heterogeneous structure with the cognitive and
      emotional signal processing ascribed to the dorsal (DH) and the ventral
      hippocampus (VH) respectively. However, the underlying mechanisms are poorly
      understood. Noradrenaline is released in hippocampus during emotional arousal
      modulating synaptic plasticity and memory consolidation through activation of
      beta adrenergic receptors (beta-ARs). Using recordings of field excitatory
      postsynaptic potentials from the CA1 field of adult rat hippocampal slices we
      demonstrate that long-term potentiation (LTP) induced either by theta-burst
      stimulation (TBS) that mimics a physiological firing pattern of hippocampal
      neurons or by high-frequency stimulation is remarkably more sensitive to beta-AR
      activation in VH than in DH. Thus, pairing of subthreshold primed burst
      stimulation with activation of beta-ARs by their agonist isoproterenol (1 MUM)
      resulted in a reliable induction of NMDA receptor-dependent LTP in the VH without
      affecting LTP in the DH. Activation of beta-ARs by isoproterenol during
      application of intense TBS increased the magnitude of LTP in both hippocampal
      segments but facilitated voltage-gated calcium channel-dependent LTP in VH only.
      Endogenous beta-AR activation contributed to the stabilization and the magnitude
      of LTP in VH but not DH as demonstrated by the effects of the beta-ARs antagonist
      propranolol (10 MUM). Exogenous (but not endogenous) beta-AR activation strongly
      increased TBS-induced facilitation of postsynaptic excitability in VH. In DH,
      isoproterenol only produced a moderate and GABAergic inhibition-dependent
      enhancement in the facilitation of synaptic burst responses. Paired-pulse
      facilitation did not change with LTP at any experimental condition suggesting
      that expression of LTP does not involve presynaptic mechanisms. These findings
      suggest that beta-AR may act as a switch that selectively promotes synaptic
      plasticity in VH through multiple ways and provide thus a first clue to
      mechanisms that underlie VH involvement in emotionality.

PMID- 29653256
TI  - Impact of Presence of Children on Indoor Tobacco Restrictions in Households of
      Urban and Rural Adult Tobacco Users.
AB  - OBJECTIVES: Secondhand smoke exposure in children is changing as a result of new
      public policy and electronic nicotine products (e-cigarettes). We examined
      factors related to self-imposed indoor household tobacco restrictions, with
      emphasis on children in the household and associations with combustible and
      noncombustible product use. METHODS: A cross-sectional survey of urban and rural
      Ohio adult tobacco users classified participants as exclusive combustible users,
      smokeless tobacco (SLT) users, e-cigarette users, or dual users. They were
      further stratified according to combustible or noncombustible product use and the
      presence of indoor tobacco use restrictions. Multiple logistic regression
      determined factors associated with indoor tobacco restrictions. RESULTS: A total
      of 1210 tobacco users participated, including 25.7% with children living in the
      home. Half allowed combustible and two thirds allowed noncombustible tobacco use
      indoors. Urban location (odds ratio [OR] = 1.58), younger age (OR = 0.88 per 5
      year), male sex (OR = 1.40), college education (OR = 1.40), household income of
      more than $15,000 (OR = 1.78), and being married (OR = 2.43) were associated with
      a higher likelihood of banning combustible products indoors. SLT (OR = 8.12) and
      e-cigarette (OR = 5.85) users were more likely to have indoor bans compared to
      combustible users. Children in the household (OR = 1.89), older age (OR = 1.12
      per 5 years), and nonwhite race (OR = 1.68) were associated with a higher
      likelihood of banning noncombustible products indoors. Combustible (OR = 4.54)
      and e-cigarette (OR = 3.04) users were more likely than SLT users to have indoor
      bans. CONCLUSIONS: Indoor restrictions on tobacco use remain infrequent in homes
      with children and are associated with user type and socioeconomic factors. Public
      policy should target modifiable risk factors for in-home secondhand smoke
      exposure.

PMID- 29653258
TI  - Cadmium inhibits lysine acetylation and succinylation inducing testicular injury
      of mouse during development.
AB  - The toxic effects of cadmium (Cd) in the reproductive system have been confirmed,
      and lysine acetylation and succinylation play important roles in spermatogenesis.
      However, little attention determined whether Cd could affect lysine acylation and
      how it might have an impact on the reproductive system. Therefore, with the goal
      of contributing to this subject, we have examined the effects of Cd on lysine
      acetylation and succinylation of proteins in the germ cells of male mice testes
      during different developmental stages. We adopted intraperitoneal injection of
      cadmium chloride (1.2 mg/kg body weight) in mice once every 5 days from postnatal
      day 5-60. The results showed that Cd could restrict GAPDH activity, ATP and cAMP
      levels of germ cells to inhibit lysine acetylation and succinylation in the
      testes, inducing reproductive injuries. Cd also restricts acetylation of histone
      H4K5 and H4K12, which could result in failure of spermiogenesis. Remarkably,
      polarized acetylation occurs in meiosis, and high-level acetylation occurs
      earlier than high-level succinylation during spermatogenesis. Moreover, Cd has a
      limited effect on body weight but reduces the weight of the testis and litter
      size. Our research may provide a new way to reveal the mechanisms of Cd
      reproductive toxicity related to lysine acetylation and succinylation.

PMID- 29653259
TI  - Bisphenol A and its derivatives decrease expression of chemerin, which reverses
      its stimulatory action in ovarian cancer cells.
AB  - Chemerin is an adipocyte-secreted protein that associates with obesity,
      inflammation, metabolic dysfunction, and carcinogenesis. Previous studies have
      shown human granulosa cells to produce bioactive chemerin and its receptor
      CMKLR1. In the present study, we demonstrated that the mRNA level of chemerin
      receptor is higher in a granulosa cell tumor cell line than in epithelial cancer
      cells, whereas chemerin expression and secretion were lower. Various exogenous
      factors, such as bisphenol A and its halogenated derivatives tetrabromobisphenol
      A and tetrachlorobisphenol A, can affect adipokine expression. For this reason,
      we investigated the effects of bisphenol A and its derivatives on the expression
      of chemerin and its receptor. At low nanomolar concentrations, BPA, TBBPA, and
      TCBPA decreased chemerin expression and secretion only in granulosa cell tumor
      COV434 cells by both peroxisome proliferator-activated receptor gamma and
      estrogen receptor signaling pathways. Chemerin treatment had no effect on
      proliferation of ovarian non-cancer and cancer cell lines. However, we also found
      evidence to support the inhibition of BPA- and TBBPA-induced cell proliferation
      by chemerin. Taken together, our results indicate for the first time that BPA and
      its derivatives down-regulate chemerin expression, which can suppress the ability
      of BPA to induce proliferation. Moreover, both PPARgamma and ERs were involved in
      the BPA-induced decrease in chemerin expression, and its ratio was crucial to
      exert these effects.

PMID- 29653260
TI  - Comparative proteomic analysis of fluoride treated rat bone provides new insights
      into the molecular mechanisms of fluoride toxicity.
AB  - Long-term excessive intake of fluoride (F) could lead to chronic fluorosis. To
      explore the underlying molecular mechanisms, present study is designed to
      elucidate the effect of fluoride on proteome expression of bone in sodium
      fluoride (NaF)-treated SD rats. Hematoxylin and eosin (H&E) staining was used to
      determine the severity of osteofluorosis, and bone samples were submitted for
      iTRAQ analysis. The results showed that the cortical thickness and trabecular
      area of femur bone in medium- and high-dose groups were higher than in control
      group. Contrary to this, trabecular area was reduced in the low-dose group,
      indicating that the bone mass was increased in medium- and high-dose groups, and
      decreased in the low-dose group. Thirteen (13), 35, and 34 differentially
      expressed proteins were identified in low-, medium-, and high-dose group,
      respectively. The medium- and high-dose groups shared a more similar protein
      expression pattern. These proteins were mainly associated with collagen
      metabolism, proteoglycans (PGs), matrix metalloproteinases (MMPs), etc. The
      results suggested that the effect of NaF on SD rats is in a dose-dependent
      manner. Some key proteins found here may be involved in affecting the bone
      tissues and bone marrow or muscle, and account for the complex pathology and
      clinical symptoms of fluorosis.

PMID- 29653261
TI  - Assessment of Obstetric and Gynecologic Food and Drug Administration Device
      Approvals and Recalls.
AB  - STUDY OBJECTIVE: To evaluate and compare the recall rates of obstetric and
      gynecologic devices approved via the Food and Drug Administration's 510(k) and
      premarket approval (PMA) processes. DESIGN: A retrospective observational study
      (Canadian Task Force classification II-2). SETTING: Clinical settings in the
      United States that use obstetric and gynecologic devices. SUBJECTS: Two thousand
      two hundred forty-nine Food and Drug Administration-approved obstetric and
      gynecologic devices that were recalled between November 1, 2002, and December 31,
      2017. MEASUREMENTS AND MAIN RESULTS: The class of device, class of recall, date
      of recall, and original approval process were obtained for each device. These
      were compared against the total number of approved devices during this time
      period in the PMA and 510(k) processes. Recall proportions of each process were
      calculated and compared. A total of 685 devices were approved via the PMA
      process, and 1564 devices were approved via the 510(k) process in the observed
      time period. Of these, 1.17% of the PMA-approved devices and 15.98% of the 510(k)
      approved devices were recalled (p < .001). There was an overall increase in
      absolute device recall numbers over time in the 510(k) process, whereas the
      number of recalls in the PMA process did not change with time. CONCLUSION: The
      recall event rate for the 510(k) approval process is 13.6 times the rate for the
      PMA approval process for obstetric and gynecologic devices. Analysis of the
      results suggests improper device risk classification, inappropriate assignment of
      the approval process, increased device malfunctions, recalls by the 510(k)
      process and, therefore, increased risk to patients by these devices. This
      warrants a call for improvement and increased scrutiny in the 510(k) approval
      process for devices used in obstetrics and gynecology.

PMID- 29653262
TI  - Laparoscopic Removal of Migration of a Chinese Ring Intrauterine Device.

PMID- 29653263
TI  - Author's Reply.

PMID- 29653264
TI  - Helminth infection in mice improves insulin sensitivity via modulation of gut
      microbiota and fatty acid metabolism.
AB  - Intestinal helminths are prevalent in individuals who live in rural areas of
      developing countries, where obesity, type 2 diabetes, and metabolic syndrome are
      rare. In the present study, we analyzed the modulation of the gut microbiota in
      mice infected with the helminth Strongyloides venezuelensis, and fed either a
      standard rodent chow diet or high-fat diet (HFD). To investigate the effects of
      the microbiota modulation on the metabolism, we analyzed the expression of tight
      junction proteins present in the gut epithelium, inflammatory markers in the
      serum and tissue and quantified glucose tolerance and insulin sensitivity and
      resistance. Additionally, the levels of lipids related to inflammation were
      evaluated in the feces and serum. Our results show that infection with
      Strongyloides venezuelensis results in a modification of the gut microbiota, most
      notably by increasing Lactobacillus spp. These modifications in the microbiota
      alter the host metabolism by increasing the levels of anti-inflammatory
      cytokines, switching macrophages from a M1 to M2 pattern in the adipose tissue,
      increasing the expression of tight junction proteins in the intestinal cells
      (thereby reducing the permeability) and decreasing LPS in the serum. Taken
      together, these changes correlate with improved insulin signaling and
      sensitivity, which could also be achieved with HFD mice treated with probiotics.
      Additionally, helminth infected mice produce higher levels of oleic acid, which
      participates in anti-inflammatory pathways. These results suggest that modulation
      of the microbiota by helminth infection or probiotic treatment causes a reduction
      in subclinical inflammation, which has a positive effect on the glucose
      metabolism of the host.

PMID- 29653265
TI  - Proteomic analysis of chemosensory organs in the honey bee parasite Varroa
      destructor: A comprehensive examination of the potential carriers for
      semiochemicals.
AB  - We have performed a proteomic analysis on chemosensory organs of Varroa
      destructor, the honey bee mite, in order to identify putative soluble carriers
      for pheromones and other olfactory cues emitted by the host. In particular, we
      have analysed forelegs, mouthparts (palps, chelicera and hypostome) and the
      second pair of legs (as control tissue) in reproductive and phoretic stages of
      the Varroa life cycle. We identified 958 Varroa proteins, most of them common to
      the different organs and stages. Sequence analysis shows that four proteins can
      be assigned to the odorant-binding protein (OBP)-like class, which bear some
      similarity to insect OBPs, but so far have only been reported in some
      Chelicerata. In addition, we have detected the presence of two proteins belonging
      to the Niemann-Pick family, type C2 (NPC2), which have also been suggested as
      semiochemical carriers. Biological significance: The mite Varroa destructor is
      the major parasite of the honey bee and is responsible for great economical
      losses. The biochemical tools used by Varroa to detect semiochemicals produced by
      the host are still largely unknown. This work contributes to understand the
      molecular basis of olfaction in Varroa and, more generally, how detection of
      semiochemicals has evolved in terrestrial non-hexapod Arthropoda. Moreover, the
      identification of molecular carriers involved in olfaction can contribute to the
      development of control strategies for this important parasite.

PMID- 29653266
TI  - Proteome-based systems biology in chronic pain.
AB  - Chronic pain represents a major medical challenge in the 21st century. Enormous
      efforts have been invested towards deciphering the complexity of chronic pain
      from different angles (molecular, physiological, psychosocial, and behavioral) in
      both preclinical and clinical settings. While progress has been made, our
      understanding of the underlying mechanisms of chronic pain remains insufficient.
      Consequently, chronic pain treatment is often inadequate. It lacks efficacy in
      most patients and is associated with detrimental side effects - a situation which
      calls for urgent changes in pain research and management. In this review we
      propose that protein-centric systems biology can significantly contribute to pain
      research. This approach may introduce the long-awaited paradigm shift in pain
      research from single targets to multidimensional cellular networks. We critically
      discuss how recent advances in reproducible and comprehensive proteome profiling
      can be exploited by pain researchers in the following ways: to gain mechanistic
      insights into chronic pain and its diverse forms, to facilitate clinical trials
      and the search for new drug targets, and to objectively assess chronic pain and
      its stages in individual patients by defining so-called protein disease
      signatures (PDS). We feel that the integration of proteomics into the toolbox of
      pain researchers and physicians alike will open new avenues towards a better
      understanding and management of chronic pain. SIGNIFICANCE STATEMENT: The immense
      challenges associated with chronic pain call for urgent changes in pain research
      and management. Here, we highlight the enormous potential of a proteome-based
      systems biology approach for advancing our understanding of chronic pain from a
      mechanistic, translational and clinical angle.

PMID- 29653267
TI  - Emerging landscape of circular RNAs in lung cancer.
AB  - Lung cancer, the leading cause of cancer deaths worldwide, is characterized with
      malignant cell growth. Advances in next-generation sequencing has helped us
      further understand RNA and identify novel circular RNAs (circRNAs) that may be
      useful in the early diagnosis and treatment of lung cancer. Similar to other
      noncoding RNAs, circRNAs present diverse biological functions in normal and
      disease states, including various types of cancers. This review focuses mainly on
      the poorly understood functions of circRNA in lung cancer. This paper also
      summarizes the recent advances in circRNA biogenesis, analyzes the role of
      circRNAs in cancers, and discusses the potential mechanisms of circRNAs in lung
      cancer.

PMID- 29653268
TI  - BBI608 inhibits cancer stemness and reverses cisplatin resistance in NSCLC.
AB  - Non-small cell lung cancer (NSCLC) is the most common cause of cancer-related
      deaths worldwide. While partial or complete tumor regression can be achieved in
      patients, particularly with cisplatin-based strategies, these initial responses
      are frequently short-lived and are followed by tumor relapse and chemoresistance.
      Identifying the root of cisplatin resistance in NSCLC and elucidating the
      mechanism(s) of tumor relapse, is of critical importance in order to determine
      the point of therapeutic failure, which in turn, will aid the discovery of novel
      therapeutics, new combination strategies and a strategy to enhance the efficacy
      of current chemotherapeutics. It has been hypothesized that cancer stem cells
      (CSCs) may be the initiating factor of resistance. We have previously identified
      and characterized an aldehyde dehydrogenase 1 CSC subpopulation in cisplatin
      resistant NSCLC. BBI608 is a small molecule STAT3 inhibitor known to suppress
      cancer relapse, progression and metastasis. Here, we show that BBI608 can inhibit
      stemness gene expression, deplete CSCs and overcome cisplatin resistance in
      NSCLC.

PMID- 29653269
TI  - MicroRNA-26a is a key regulon that inhibits progression and metastasis of c
      Myc/EZH2 double high advanced hepatocellular carcinoma.
AB  - The transcription factor c-Myc is a key driver for hepatocellular carcinomas
      (HCCs), while the polycombrepressive complex 2 (PRC2) subunit EZH2 is an
      essential biomarker of HCC. c-Myc epigenetically silences tumor suppressors by
      recruiting PRC2 and inducing methylation of histone H3 lysine 27. However, it
      remains elusive how they are regulated in HCC. We found here that microRNA-26a
      (miR-26a) suppresses c-Myc, a classical Wnt pathway target gene, by targeting the
      Wnt pathway coactivator, cyclin-dependent kinase 8 (CDK8); miR-26a also directly
      targets and inhibits EZH2. The expression of MIR26A2, a predominant origin of miR
      26a transcripts in hepatic cells, is repressed by c-Myc/PRC2, thereby forming a c
      Myc/miR-26a/CDK8 regulatory circuit in HCC. Meanwhile, miR-26a suppresses
      migration of HCC by targeting p21-activated kinase 2 (PAK2), a critical kinase
      linking Rho GTPases to cytoskeleton reorganization. Consequently, in vivo
      delivery of miR-26a remarkably suppressed the development of xenograft HCC and
      metastasis of orthotopic HCC by downregulating c-Myc, CDK8 and PAK2. These
      findings unraveled a novel mechanism of c-Myc and Wnt/beta-catenin interplay that
      dictates HCC pathogenesis, and have implications for the potential applicability
      of miRNA delivery in targeting the newly identified signaling axis and treating
      metastatic HCCs.

PMID- 29653270
TI  - Decompressive Craniotomy for Malignant Middle Cerebral Artery Infarction: Optimal
      Timing and Literature Review.
AB  - OBJECTIVE: To compare the results of early or delayed decompressive craniotomy
      for patients with malignant middle cerebral artery infarction. METHODS: A
      prospective randomized study was carried out of a series of 46 consecutive
      patients with malignant middle cerebral artery territory infarction. Patients
      were divided randomly into 2 groups: group I, 27 patients who were followed until
      obvious deterioration of level of consciousness; group II, 19 patients who were
      operated on prophylactically in 6 hours of presentation even with no clear
      deterioration of level of consciousness or radiologic findings. Patients were
      assessed clinically using the Glasgow Coma Scale, motor power by the United
      Kingdom Medical Research Council, and functionally by the National Institutes of
      Health Stroke Scale and modified Rankin Scale. Radiologically, patients had
      primary magnetic resonance imaging on admission, followed by computed tomography
      scan. Infarction behavior including volume of infarct area, midline shift, and
      secondary hemorrhage were calculated. RESULTS: At final follow-up, both groups
      showed good improvement in level of consciousness, motor power, and functional
      outcome; however, statistically significant neurologic improvement was shown in
      group II. Functional outcome also showed statistically significant improvement (P
      < 0.05) in this ultraearly decompression group (group II). There was a
      significant difference in mortality in both groups; more than half (52%) of group
      I died as a result of delay in surgery or its other consequences. Another
      significant difference was in the progression of infarction volume, which was
      observed more in group I (statistically insignificant). CONCLUSIONS: Despite the
      possible complications from surgery, early decompressive craniotomy (within 6
      hours of ictus without waiting for neurologic deterioration) has a significant
      impact on prognosis. Delay in transferring the patient, diagnosing the condition,
      or taking the decision of surgery significantly affects mortality and overall
      outcome.

PMID- 29653271
TI  - Risk Factors, Additional Length of Stay, and Cost Associated with Postoperative
      Ileus Following Anterior Lumbar Interbody Fusion in Elderly Patients.
AB  - OBJECTIVE: To identify independent risk factors, additional length of stay, and
      additional cost associated with postoperative ileus following anterior lumbar
      interbody fusion in elderly patients. METHODS: The PearlDiver Patient Records
      Database was queried for all Medicare patients >=65 years of age undergoing 1- or
      2-level primary elective anterior lumbar interbody fusion from 2005 to 2014.
      Independent risk factors, additional length of stay, and additional cost
      associated with postoperative ileus were evaluated with multivariate analysis.
      RESULTS: There were 13,139 patients identified, and 642 patients experienced
      postoperative ileus within 3 days after surgery. Multivariate analysis identified
      perioperative fluid or electrolyte imbalance (odds ratio = 4.03; 95% confidence
      interval, 3.37-4.80; P < 0.001) and male sex (odds ratio = 1.72; 95% confidence
      interval, 1.48-2.00; P < 0.001) as independent risk factors for ileus.
      Multivariate analysis associated postoperative ileus with additional length of
      stay of 2.83 +/- 0.11 days (P < 0.001) and additional cost of $2,349 +/- $419 (P
      < 0.001). CONCLUSIONS: Patients with perioperative fluid and electrolyte
      imbalances were 4 times as likely to experience postoperative ileus. Fluid
      balance and electrolyte levels should be carefully monitored during the
      perioperative period in patients undergoing anterior lumbar interbody fusion as a
      potential means to reduce the incidence of postoperative ileus and the additional
      length of stay and cost burden associated with this complication.

PMID- 29653272
TI  - Evaluation of Microsurgery for Managing Giant or Complex Cerebral Aneurysms: A
      Retrospective Study.
AB  - OBJECTIVE: Surgical or endovascular treatment for giant or complex aneurysms is
      challenging. The aims of this study were to evaluate clinical outcomes and
      factors affecting the prognosis of giant or complex aneurysms and to better
      establish the role of microsurgery in the management strategy. METHODS: One
      hundred fifty-nine patients with surgically treated complex aneurysms were
      included. Thirty-two patients (20.1%) had giant aneurysms (>=25 mm) and 57
      (35.8%) had large aneurysms (>=15 mm). Poor outcome was defined as modified
      Rankin Scale scores of 3-6. RESULTS: The mean aneurysm size was 17.0 mm (range,
      1.6-47.5 mm). One hundred and sixteen aneurysms (80.0%) were in the anterior
      circulation and 43 (27.0%) were in the posterior circulation. One hundred and
      thirty-eight (86.8%) aneurysms were completely occluded without residual
      aneurysms. Nineteen (11.9%) had minor aneurysm remnants; 2 (1.3%) had incomplete
      occlusion. Two patients (1.3%) with giant basilar artery (BA) trunk aneurysms
      experienced rupture of the treated aneurysm and died. Bypass surgery was combined
      with microsurgery in 148 patients (93.1%). Perforating artery infarction was
      observed postoperatively in 42 patients (26.4%), and poor outcome was observed in
      29 (18.2%). Male sex (P = 0.016; adjusted odds ratio [OR], 4.524 [1.949-10.500]),
      perforating artery infarction (P < 0.001; adjusted OR, 13.625 [5.329-34.837]),
      and BA aneurysm location (P = 0.003; adjusted OR, 56.333 [6.830-464.657]) were
      significantly related to poor outcome. The aneurysm size (P = 0.017; adjusted OR,
      1.064 [1.021-1.107]), C1 aneurysm location (P = 0.042; adjusted OR, 2.591 [0.986
      6.811]), and BA aneurysm location (P = 0.033; adjusted OR, 12.956 [3.197-52.505])
      were significantly related to perforating artery infarction. CONCLUSIONS:
      Microsurgery with bypass is effective for many different complex aneurysms,
      except BA aneurysms.

PMID- 29653273
TI  - Jacques-Joseph Bonhomme (1708-1793): Forgotten French Neuroanatomist and Surgeon.
AB  - Although relatively little has been written of Jacques-Joseph Bonhomme's life
      (1708-1793) and contribution, his descriptions of the brain "Traite de la
      Cephalotomie" (Treatise on Dissection of the Head) were among the most accurate
      of his day. Published in 1748 in Avignon (France), this book remained a valuable
      resource to anatomists and surgeons as it was highlighted in many publications.
      Bonhomme was one of the first surgeons to study brain details in the skull's
      natural position. The brain was cut perpendicularly along the median line with
      new techniques of dissection (by the bottom of the head and not by the top). He
      has also been known for the accuracy of his illustrations. Bonhomme was appointed
      anatomic demonstrator at the Hospital and the University of Avignon, a
      prestigious position for a former "barber surgeon" at that time. His literary
      merits established him as a respected scholar of neuroanatomy during his
      lifetime. However, he did not have such a wide European reputation, probably
      because he had no access to a chair of anatomy.

PMID- 29653274
TI  - Letter to the Editor Regarding "Association Between Blood Glucose and Functional
      Outcome in Intracerebral Hemorrhage: A Systematic Review and Meta-analysis".

PMID- 29653275
TI  - Safety and Efficacy of Flow Diverter Treatment for Aneurysm in Small Cerebral
      Vessels: A Systematic Review and Meta-Analysis.
AB  - PURPOSE: To clarify the safety and efficacy of flow diverter (FD) treatment for
      aneurysm in small cerebral vessels, we conducted a systematic review of the
      literature analyzing perioperative and long-term clinical and angiographic
      outcomes. METHODS: A comprehensive review of the up-to-date literature for
      studies with >=10 patients related to FD treatment of small vessel aneurysms
      published was performed. Random-effects meta-analysis was used to pool the
      following outcomes: complete occlusion, technical procedural success,
      perioperative mortality, perioperative stroke, procedure-related morbidity and
      mortality, all complications, long-term mortality, and overall good outcome.
      RESULTS: We included 26 noncomparative studies with 572 target aneurysms. The
      technical procedural success rate was 96% (95% confidence interval [CI] 0.93
      1.00). At final follow-up, the complete occlusion rate was 70% (95% CI 0.64
      0.76). The all-cause morbidity rate was 20% (95% CI 0.14-0.25). Procedure-related
      morbidity and mortality rates were 9% (95% CI 0.07-0.12) and 4% (95% CI 0.00
      0.08), respectively. Overall long-term good outcome rate was 96% (95% CI 0.93
      0.99). In the 3 subgroup analyses, complete occlusion rate of saccular aneurysms
      was lower than that of nonsaccular aneurysms (55% vs. 73%, respectively; odds
      ratio 0.40, 95% CI 0.17-0.98, P = 0.04). The procedure-related morbidity rate and
      the good outcome rate were not significantly different in this subgroup. In the
      other 2 subgroups in which we compared anterior circulation aneurysms with
      posterior circulation aneurysms and single FD strategy with overlapped FD
      strategy, the rates were also not significantly different. CONCLUSIONS: Our meta
      analysis demonstrated that FD treatment of small vessel aneurysms is technically
      feasible and effective with a high rate of complete occlusion. Although the
      comorbidities of patients cannot be neglected, the FD approach was associated
      with an acceptable rate of procedure-related morbidity and a satisfactory rate of
      overall good outcome.

PMID- 29653276
TI  - In Vivo Microscopy in Neurosurgical Oncology.
AB  - Intraoperative neurosurgical histopathologic diagnoses rely on evaluation of
      rapid tissue preparations such as frozen sections and smears with conventional
      light microscopy. Although useful, these techniques are time consuming and
      therefore cannot provide real-time intraoperative feedback. In vivo molecular
      imaging techniques are emerging as novel methods for generating real-time
      diagnostic histopathologic images of tumors and their surrounding tissues. These
      imaging techniques rely on contrast generated by exogenous fluorescent dyes,
      autofluorescence of endogenous molecules, fluorescence decay of excited
      molecules, or light scattering. Large molecular imaging instruments are being
      miniaturized for clinical in vivo use. This review discusses pertinent imaging
      systems that have been developed for neurosurgical use and imaging techniques
      currently under development for neurosurgical molecular imaging.

PMID- 29653277
TI  - "Crick" in Neck Followed by Massage Led to Stroke: Uncommon Case of Vertebral
      Artery Dissection.
AB  - BACKGROUND: Vertebral artery dissection (VAD) is an important cause of stroke in
      young and a known complication of spinal manipulation procedures, although
      dissection following neck massage has rarely been reported in literature. Head
      and neck massage by improperly trained salon employees is very popular and widely
      practiced in developing countries like India. In the present report we present a
      case of VAD following neck massage. MATERIAL AND METHODS: We present an unusual
      case of VAD in a 30-year-old male patient following an episode of neck massage.
      He developed headache, nausea, vomiting, blurred vision, diplopia, dizziness, and
      ataxia following the procedure. Initial history and examination suggested that
      the patient's symptoms were vascular in origin. We also discuss a brief review of
      the pathology, diagnosis, symptomatology, treatment, prognosis, and occurrence of
      this rare entity. RESULTS: Computed tomography and magnetic resonance imaging of
      the brain revealed acute infarction of the left cerebellar hemisphere. Digital
      subtraction angiography showed narrowing and dilatation of the V3 segment of the
      left vertebral artery with narrowing of the V4 segment consistent with
      dissection, along with a cavernous segment aneurysm of the contralateral internal
      carotid artery. CONCLUSION: This report illustrates the potential hazards
      associated with neck massage. The vertebral arteries are at risk for dissection,
      which can lead to acute stroke. This case also suggests that careful history
      taking and awareness of the symptoms of VAD are necessary to diagnose this entity
      as timely diagnosis and treatment can prevent permanent disability or even death.

PMID- 29653278
TI  - Psychometric Validation of the Korean Version of the Camberwell Assessment of
      Need for the Elderly (CANE-K) in Dementia.
AB  - PURPOSE: The prevalence of dementia has increased rapidly with an aging Korean
      population. Compared to those without dementia, individuals with dementia have
      more and complex needs. In this study, the Korean version of the Camberwell
      Assessment of Need for the Elderly (CANE-K) was evaluated to determine its
      suitability for individuals with dementia in Korea. METHODS: The CANE-K was
      developed following linguistic validation. The reliability of the measurement was
      examined with Cronbach's alpha coefficient. The factor structure and construct
      validity were evaluated by performing exploratory factor analysis (EFA) and
      confirmatory factor analyses (CFA). Pearson's correlation coefficients with
      related measures were used to ensure concurrent validity. RESULTS: Four factors
      extracted with EFA and CFA validated the model structure (X2 = 367.25, p = .000,
      goodness of fit index = .84, adjusted goodness of fit index = .80, root mean
      square error of approximation = .07, and comparative fit index = .83). Items on
      the CANE-K loaded on the four factors in a range between .40 and .80. The output
      of Pearson's correlation coefficient with cognitive impairment, behavioral
      problems, activities of daily living and caregiver burden showed acceptable
      concurrent validity. CONCLUSION: The CANE-K showed a reasonable degree of
      reliability and validity. Therefore, it has good potential to appropriately
      measure the needs and unmet needs of those with dementia.

PMID- 29653279
TI  - The impact of auditory white noise on semantic priming.
AB  - It has been proposed that white noise can improve cognitive performance for some
      individuals, particularly those with lower attention, and that this effect may be
      mediated by dopaminergic circuitry. Given existing evidence that semantic priming
      is modulated by dopamine, this study investigated whether white noise can
      facilitate semantic priming. Seventy-eight adults completed an auditory semantic
      priming task with and without white noise, at either a short or long inter
      stimulus interval (ISI). Measures of both direct and indirect semantic priming
      were examined. Analysis of the results revealed significant direct and indirect
      priming effects at each ISI in noise and silence, however noise significantly
      reduced the magnitude of indirect priming. Analyses of subgroups with higher
      versus lower attention revealed a reduction to indirect priming in noise relative
      to silence for participants with lower executive and orienting attention. These
      findings suggest that white noise focuses automatic spreading activation, which
      may be driven by modulation of dopaminergic circuitry.

PMID- 29653280
TI  - The beneficial effect of a speaker's gestures on the listener's memory for action
      phrases: The pivotal role of the listener's premotor cortex.
AB  - Memory for action phrases improves in the listeners when the speaker accompanies
      them with gestures compared to when the speaker stays still. Since behavioral
      studies revealed a pivotal role of the listeners' motor system, we aimed to
      disentangle the role of primary motor and premotor cortices. Participants had to
      recall phrases uttered by a speaker in two conditions: in the gesture condition,
      the speaker performed gestures congruent with the action; in the no-gesture
      condition, the speaker stayed still. In Experiment 1, half of the participants
      underwent inhibitory rTMS over the hand/arm region of the left premotor cortex
      (PMC) and the other half over the hand/arm region of the left primary motor
      cortex (M1). The enactment effect disappeared only following rTMS over PMC. In
      Experiment 2, we detected the usual enactment effect after rTMS over vertex,
      thereby excluding possible nonspecific rTMS effects. These findings suggest that
      the information encoded in the premotor cortex is a crucial part of the memory
      trace.

PMID- 29653282
TI  - Dropped head syndrome with proximal myopathy revealing AL amyloidosis.

PMID- 29653281
TI  - Intrauterine and lactational exposure to fluoxetine enhances endothelial
      modulation of aortic contractile response in adult female rats.
AB  - The study aimed to evaluate if maternal exposure to fluoxetine (FLX) during
      pregnancy and lactation would result in altered aortic reactivity in adult
      offspring. We also sought to understand the role of endothelium derived relaxing
      factors in aortic response. Wistar rats (75-80 days old), whose progenitors had
      received FLX (5 mg/kg, FLX offspring) or tap water (control offspring) during
      pregnancy and lactation were anesthetized, after which the aorta was removed and
      cut into two rings, one with (Endo+) and the other without (Endo-) endothelium.
      Concentration-effect curves for acetylcholine (ACh), sodium nitroprusside (SNP),
      and phenylephrine (Phe) were performed. The vasodilation to ACh and SNP was
      similar between control and FLX groups in both male and female offspring. In male
      rats, the response to Phe was similar between the FLX and control groups on Endo+
      and Endo- rings. The response to Phe was reduced on Endo+ rings from female FLX
      when compared with the control group. The endothelium removal, as well as L-NAME,
      indomethacin, and tranylcypromine incubation corrected the reduced Phe-induced
      contraction in the aorta from the female FLX group. On the other hand, catalase,
      NS-398, and L-NIL did not interfere with the vasoconstriction. The aortic level
      of nitric oxide (NO) washigher in the female FLX than the control group. Although
      endothelial NO synthase isoform and cyclooxygenase (COX)-1 expressions were
      similar between the groups, there was a notable increment in neuronal NO synthase
      expression in the aorta of FLX-exposed female rats, suggesting an important role
      of this enzyme in the higher levels of NO. Our results show that developmental
      exposure to FLX causes sex-specific alteration in aorticfunction through a
      mechanism involving endothelial factors, probably NO and COX-1 products.

PMID- 29653283
TI  - Camptocormia with trigeminal involvement revealing myositis with anti-Ku
      antibodies.

PMID- 29653284
TI  - A 3-year back and forth between Modic type 1 and 2 on MRI in chronic low back
      pain.

PMID- 29653285
TI  - Adipokines and bone status in a cohort of anorexic patients.
AB  - INTRODUCTION: Bone loss in anorexia nervosa (AN) is multifactorial; its
      mechanisms are not yet clearly understood and may vary depending on disease
      duration and severity. To determine to what extent adipokines may be involved in
      the bone alterations found in anorexic patients, we evaluated plasma levels for
      leptin, adiponectin and Pref-1 against other clinical and biological parameters
      in a population of anorexic patients split according to weight and bone status.
      METHODS: Plasma concentrations of leptin, total adiponectin, high molecular
      weight (HMW) adiponectin, and Pref-1 were measured. The ratio of HMW adiponectin
      to total adiponectin - HMW (percentage) - was calculated. We divided our
      population into 5 groups with different phenotypes characterizing the severity of
      the disease and/or the severity of bone involvement: 1 - Normal BMD and body mass
      index (BMI): recovery from AN; 2 - Osteopenia (-2<Z-score<-1) and BMI>17kg/m2; 3 
      Osteopenia and BMI<=17kg/m2; 4 - Osteoporosis (Z-score<=-2) and BMI>17kg/m2; 5 -
      Osteoporosis and BMI<=17kg/m2. RESULTS: The study involved 80 anorexia nervosa
      patients. Mean BMI was 16.8+/-2.4kg/m2. No significant difference was found in
      total and HMW adiponectin plasma concentrations between the 5 groups. HMW
      (percentage) was significantly higher in group 5 compared to group 1. Leptin was
      significantly lower in groups 3 and 5 compared to the other groups. For the whole
      group femoral neck and hip BMD correlated negatively with total adiponectin and
      HMW adiponectin. No correlation was found between BMD (whatever the site) and
      plasma leptin. Multivariate analysis revealed that 2 factors - leptin and BMI -
      explained 10% of the variance in spine BMD. For femoral neck BMD, the 2
      explanatory factors were BMI and total adiponectin which explained 14% of the
      variance in BMD. For total hip BMD, 27% of the variance in BMD was explained by 3
      factors: leptin, BMI, and total adiponectin. CONCLUSION: Bone status in anorexia
      nervosa is mainly determined by BMI, leptin and adiponectin.

PMID- 29653286
TI  - Stromal cell-laden 3D hydrogel microwell arrays as tumor microenvironment model
      for studying stiffness dependent stromal cell-cancer interactions.
AB  - Tumor properties such as growth and metastasis are dramatically dependent on the
      tumor microenvironment (TME). However, the diversity of the TME including the
      stiffness and the composition of the extracellular matrix (ECM), as well as the
      involvement of stromal cells, makes it extremely difficult to establish proper in
      vitro models for studying tumor growth and metastasis. In this research, we
      fabricated a stromal cell-laden microwell array system with tunable stiffness
      ranging from 200 Pa up to 3 kPa, which covers the stiffness range of normal and
      cancerous mammary tissues, to study the effect of ECM stiffness on stromal-cancer
      interaction. Our results showed that, tumor spheroids closely interacted with the
      pre-adipocyte stromal cells encapsulated within the microwell array, influencing
      their differentiation and maturation degree in a stiffness related manner. They
      inhibited adipogenesis in high stiffness tissue constructs that were at breast
      cancer stiffness range, while the inhibition effect diminished in the low
      stiffness tissue constructs that were at normal human breast tissue range.
      Furthermore, the 3D structure of tumor spheroids was shown to be important for
      the inhibition of the adipogenesis, as conditioned media from monolayer culture
      of cancer cells did not show any significant effect. These results show, for the
      first time in literature, that stromal-cancer interactions are highly dependent
      on ECM stiffness. The biomimetic TME platform developed here is a powerful organ
      specific cancer model for studying the involvement of stromal cells in early
      mammary tumorigenesis and metastasis, and could be powerful platform for high
      throughput drug discovery.

PMID- 29653288
TI  - pH protective Y1 receptor ligand functionalized antiphagocytosis BPLP-WPU
      micelles for enhanced tumor imaging and therapy with prolonged survival time.
AB  - Nanoparticle-based tumor therapies are extensively studied; however, few are
      capable of improving patient survival time due to premature drug leakage, off
      target effects, and poor tissue penetration. Previously, we successfully
      synthesized a novel family of Y1 receptor (Y1R) ligand modified, photoluminescent
      BPLP nanobubbles and nanoparticles for targeted breast cancer ultrasound imaging;
      however, increased accumulation could also be observed in the liver, kidney, and
      spleen, suggesting significant interaction of the particles with macrophages in
      vivo. Herein, for the first time, we imparted antiphagocytosis capability to Y1R
      ligand functionalized BPLP-WPU polymeric micelles through the incorporation of a
      CD47 human glycoprotein based self-peptide. Application of self-peptide modified,
      DOX loaded micelles in vivo resulted in a 100% survival rate and complete tumor
      necrosis over 100 days of treatment. In vivo imaging of SPION loaded, self
      peptide modified micelles revealed effective targeting to the tumor site while
      analysis of iron content demonstrated reduced particle accumulation in the liver
      and kidney, demonstrating reduced macrophage interaction, as well as a 2-fold
      increase of particles in the tumor. As these results demonstrate, Y1R ligand,
      self-peptide modified BPLP-WPU micelles are capable of target specific cancer
      treatment and imaging, making them ideal candidates to improve survival rate and
      tumor reduction clinically.

PMID- 29653287
TI  - Detecting the functional complexities between high-density lipoprotein mimetics.
AB  - High-density lipoprotein (HDL) is a key regulator of lipid homeostasis through
      its native roles like reverse cholesterol transport. The reconstitution of this
      natural nanoparticle (NP) has become a nexus between nanomedicine and multi
      disease therapies, for which a major portion of HDL functionality is attributed
      to its primary scaffolding protein, apolipoprotein A1 (apoA1). ApoA1-mimetic
      peptides were formulated as cost-effective alternatives to apoA1-based therapies;
      reverse-4F (r4F) is one such peptide used as part of a nanoparticle platform.
      While similarities between r4F- and apoA1-based HDL-mimetic nanoparticles have
      been identified, key functional differences native to HDL have remained
      undetected. In the present study, we executed a multidisciplinary approach to
      uncover these differences by exploring the form, function, and medical
      applicability of engineered HDL-mimetic NPs (eHNPs) made from r4F (eHNP-r4F) and
      from apoA1 (eHNP-A1). Comparative analyses of the eHNPs through computational
      molecular dynamics (MD), advanced microfluidic NP synthesis and screening
      technologies, and in vivo animal model studies extracted distinguishable eHNP
      characteristics: the eHNPs share identical structural and compositional
      characteristics with distinct differences in NP stability and organization; eHNP
      A1 could more significantly stimulate anti-inflammatory responses characteristic
      of the scavenger receptor class B type 1 (SR-B1) mediated pathways; and eHNP-A1
      could outperform eHNP-r4F in the delivery of a model hydrophobic drug to an in
      vivo tumor. The biomimetic microfluidic technologies and MD simulations uniquely
      enabled our comparative analysis through which we determined that while eHNP-r4F
      is a capable NP with properties mimicking natural eHNP-A1, challenges remain in
      reconstituting the full functionality of NPs naturally derived from humans.

PMID- 29653289
TI  - Src activation decouples cell division orientation from cell geometry in
      mammalian cells.
AB  - Orientation of cell division plane plays a crucial role in morphogenesis and
      regeneration. Misoriented cell division underlies many important diseases, such
      as cancer. Studies with Drosophila and C. elegance models show that Src, a proto
      oncogene tyrosine-protein kinase, is a critical regulator of this aspect of
      mitosis. However, the role for Src in controlling cell division orientation in
      mammalian cells is not well understood. Using genetic and pharmacological
      approaches and two extracellular signals to orient cell division, we demonstrated
      a critical role for Src. Either knockout or pharmacological inhibition of Src
      would retain the fidelity of cell division orientation with the long-axis
      orientation of mother cells. Conversely, re-expression of Src would decouple cell
      division orientation from the pre-division orientation of the long axis of mother
      cells. Cell division orientation in human breast and gastric cancer tissues
      showed that the Src activation level correlated with the degree of mitotic
      spindle misorientation relative to the apical surface. Examination of proteins
      associated with cortical actin revealed that Src activation regulated the
      accumulation and local density of adhesion proteins on the sites of cell-matrix
      attachment. By analyzing division patterns in the cells with or without Src
      activation and through use of a mathematical model, we further support our
      findings and provide evidence for a previously unknown role for Src in regulating
      cell division orientation in relation to the pre-division geometry of mother
      cells, which may contribute to the misoriented cell division.

PMID- 29653290
TI  - Paternal Disease Activity Is Associated With Difficulty in Conception Among Men
      With Inflammatory Bowel Diseases.

PMID- 29653292
TI  - The study on polymorphisms of Sep15 and TrxR2 and the expression of AP-1
      signaling pathway in Kashin-Beck disease.
AB  - The aim of the study was to investigate the association between rs5859 in Sep15,
      rs1139793 in TrxR2 polymorphisms with the risks of KBD and to detect the
      expression of AP-1 pathway in KBD subjects and in vitro. 208 KBD and 206 control
      subjects were included. PCR-Restriction Fragment Length Polymorphism (RFLP),
      Amplification Refractory Mutation Specific-PCR (ARMS-PCR) and Western Blotting
      were conducted. The results showed the minor A-allele frequency of rs5859 in KBD
      was statistically significantly higher than that in the control group (P < 0.05).
      The cases carrying A-allele had a 2-fold (95%CI: 1.064-3.956) increased risk of
      developing KBD compared with the G-allele carriers. There was no significant
      difference in genotype and allele distribution of rs1139793 between KBD patients
      and controls (P > 0.05). The frequency of the minor A allele of rs5859 was
      significantly different in Chinese healthy population compared with European,
      African and American. The frequency of the minor A allele of rs1139793 showed
      significant difference when compared with African and American. The levels of
      JunB, JunD, P65 proteins in KBD group were higher than those in control group (P
      < 0.0001). The expression of JunB, JunD, P65 proteins all increased in tBHP
      induced C28/I2 oxidative damage model compared with control group (P < 0.05) and
      decreased after Se supplementation. Our finding indicated Sep15 is a possible
      candidate susceptibility gene for KBD. Combined with the in vitro study, our
      studies reveal novel insights into the mechanism of Se supplementation as an
      antioxidant via inhibiting the AP-1 signaling pathway in patients with KBD.

PMID- 29653293
TI  - Transcriptional profiling of murine osteoblast differentiation based on RNA-seq
      expression analyses.
AB  - Osteoblastic differentiation is a multistep process characterized by osteogenic
      induction of mesenchymal stem cells, which then differentiate into proliferative
      pre-osteoblasts that produce copious amounts of extracellular matrix, followed by
      stiffening of the extracellular matrix, and matrix mineralization by
      hydroxylapatite deposition. Although these processes have been well characterized
      biologically, a detailed transcriptional analysis of murine primary calvaria
      osteoblast differentiation based on RNA sequencing (RNA-seq) analyses has not
      previously been reported. Here, we used RNA-seq to obtain expression values of
      29,148 genes at four time points as murine primary calvaria osteoblasts
      differentiate in vitro until onset of mineralization was clearly detectable by
      microscopic inspection. Expression of marker genes confirmed osteogenic
      differentiation. We explored differential expression of 1386 protein-coding genes
      using unsupervised clustering and GO analyses. 100 differentially expressed
      lncRNAs were investigated by co-expression with protein-coding genes that are
      localized within the same topologically associated domain. Additionally, we
      monitored expression of 237 genes that are silent or active at distinct time
      points and compared differential exon usage. Our data represent an in-depth
      profiling of murine primary calvaria osteoblast differentiation by RNA-seq and
      contribute to our understanding of genetic regulation of this key process in
      osteoblast biology.

PMID- 29653291
TI  - Design strategies for physical-stimuli-responsive programmable nanotherapeutics.
AB  - Nanomaterials that respond to externally applied physical stimuli such as
      temperature, light, ultrasound, magnetic field and electric field have shown
      great potential for controlled and targeted delivery of therapeutic agents.
      However, the body of literature on programming these stimuli-responsive
      nanomaterials to attain the desired level of pharmacologic responses is still
      fragmented and has not been systematically reviewed. The purpose of this review
      is to summarize and synthesize the literature on various design strategies for
      simple and sophisticated programmable physical-stimuli-responsive
      nanotherapeutics.

PMID- 29653294
TI  - Sclerostin vaccination mitigates estrogen deficiency induction of bone mass loss
      and microstructure deterioration.
AB  - Sclerostin (SOST) is a Wnt signaling inhibitor detrimental to osteogenic
      differentiation and bone mineral acquisition. While control of SOST action delays
      the pathogenesis of skeletal disorders, the effects of SOST vaccination on the
      estrogen deficiency-induced bone deterioration remain elusive. In this study, we
      generated a SOST-Fc fusion protein which was composed of a SOST peptide Pro-Asn
      Ala-Ile-Gly along with an IgG Fc fragment. SOST-Fc vaccination increased serum
      anti-SOST antibody levels and reduced serum SOST concentrations in mice. In
      vitro, anti-SOST serum attenuated the SOST-induced inhibition of osteogenic gene
      expression in osteoblast cultures. Administration with SOST-Fc increased serum
      levels of bone formation marker osteocalcin and alleviated the ovariectomy
      escalation of serum resorption markers CTX-1 and TRAP5b concentrations. It
      remarkably lessened the estrogen deficiency-mediated deterioration of bone
      mineral density, morphometric characteristics of trabecular bone, and mechanical
      strength of femurs and lumbar spines. The SOST-Fc-treated skeletal tissue
      exhibited moderate responses to the adverse actions of ovariectomy to bone
      mineral accretion, osteoclast surface, trabecular separation, and fatty marrow
      histopathology. SOST-Fc treatment increased serum osteoclast-inhibitory factor
      osteoprotegrin levels in conjunction with strong Wnt3a, beta-catenin, and TCF4
      immunostaining in osteoblasts, whereas it weakened the estrogen deficiency
      enhancement of osteoclast-promoting factor receptor activator of nuclear factor
      kappaB ligand. Taken together, blockade of SOST action by SOST-Fc vaccination
      sustains Wnt signaling, which harmonizes bone mineral accretion and resorption
      reactions and thereby ameliorates ovariectomy-induced bone loss. This study
      highlights SOST-Fc fusion protein as a new molecular therapeutic potential for
      preventing from osteoporotic disorders.

PMID- 29653295
TI  - Feasibility of a mindfulness-based cognitive therapy group intervention as an
      adjunctive treatment for postpartum depression and anxiety.
AB  - BACKGROUND: Many women experience moderate-to-severe depression and anxiety in
      the postpartum period for which pharmacotherapy is often the first-line
      treatment. Many breastfeeding mothers are reticent to increase their dose or
      consider additional medication, despite incomplete response, due to potential
      adverse effects on their newborn. These mothers are amenable to non
      pharmacological intervention for complete symptom remission. The current study
      evaluated the feasibility of an eight-week mindfulness-based cognitive therapy
      (MBCT) intervention as an adjunctive treatment for postpartum depression and
      anxiety. METHODS: Women were recruited at an outpatient reproductive mental
      health clinic based at a maternity hospital. Participants had a diagnosis of
      postpartum depression/anxiety within the first year following childbirth. They
      were enrolled in either the MBCT intervention group (n = 14) or the treatment-as
      usual control group (n = 16), and completed the Patient Health Questionnaire-9
      (PHQ-9), the Generalized Anxiety Disorder-7 (GAD-7) questionnaire, and the
      Mindful Attention Awareness Scale (MAAS) at baseline and at 4 weeks, 8 weeks, and
      3 months following baseline. RESULTS: Multivariate analyses demonstrated that
      depression and anxiety levels decreased, and mindfulness levels increased, in the
      MBCT group, but not in the control group. Many of the between-group and over time
      comparisons displayed trends towards significance, although these differences
      were not always statistically significant. Additionally, the effect sizes for
      anxiety, depression, and mindfulness were frequently large, indicating that the
      MBCT intervention may have had a clinically significant effect on participants.
      LIMITATIONS: Limitations include small sample size and the non-equivalent control
      group design. CONCLUSIONS: We demonstrated that MBCT has potential as an
      adjunctive, non-pharmacological treatment for postpartum depression/anxiety that
      does not wholly remit with pharmacotherapy. (249 words).

PMID- 29653296
TI  - The role of resting-state EEG localized activation and central nervous system
      arousal in executive function performance in children with Attention
      Deficit/Hyperactivity Disorder.
AB  - OBJECTIVE: This study explored the relationships between resting-state
      electroencephalogram (RS-EEG) localized activation and two important types of
      executive functions (EF) to extend the prognostic utilization of RS-EEG in
      children with Attention-Deficit/Hyperactivity Disorder (AD/HD). Also, the role of
      central nervous system (CNS) arousal in the relationships was examined. METHODS:
      Fifty-eight children with AD/HD participated in the study. RS-EEG localized
      activation was derived from spectral power differences between EEG in eyes-closed
      and eyes-open conditions. CNS arousal was measured based on alpha band power.
      Common and everyday EF scores were obtained as EF outcomes. RESULTS: Frontal
      delta activation predicted common EF ability and posterior alpha activation
      predicted everyday EF. A serial mediation analysis found that lower CNS baseline
      arousal was related to greater arousal and delta activation in series, which in
      turn related to worse common EF. A follow-up study found that baseline arousal
      was related to larger interference cost. CONCLUSIONS: RS-EEG is indicative of
      individual differences in two important types of EF in children with AD/HD. Lower
      CNS arousal may be a driving force for the poorer common EF performance.
      SIGNIFICANCE: The current study supports prognostic utilization of RS-EEG and
      AD/HD models that take resting brain activity into consideration in children with
      AD/HD.

PMID- 29653297
TI  - The efficacy of transcranial random noise stimulation (tRNS) on mood may depend
      on individual differences including age and trait mood.
AB  - OBJECTIVES: To assess whether changes in brain microstructures associated with
      ageing and presence of cardiovascular risk factors (CVRF) reduce the efficacy of
      transcranial electrical stimulation (tES) improving mood in euthymic older
      adults. METHODS: Using excitatory high-frequency transcranial random noise
      stimulation (tRNS) over bilateral dorsolateral prefrontal cortex, the effect on
      mood was assessed in euthymic young adults (YA), older adults (HOA) and older
      adults with CVRF (OVR). Active-tRNS or sham was applied over two sessions.
      Positive and Negative Affect Schedule and Warwick Edinburgh Mental Well-being
      Scale measured self-reported state mood before and after stimulation. Trait mood
      was also measured using the Geriatric Depression Scale. RESULTS: Response to tRNS
      seemed dependent on individual differences in age and trait mood. In HOA, more
      negative trait mood was associated with more positive mood change after tRNS. OVR
      showed a similar but reduced pattern of mood change to HOA. In YA, more positive
      trait mood was associated with greater positive mood change after tRNS.
      CONCLUSIONS: Age and trait mood may be important factors when examining the
      efficacy of tES as an alternative treatment for depression. SIGNIFICANCE: Future
      studies should consider how response to tES is affected by individual
      differences.

PMID- 29653299
TI  - Confocal total reflection X-ray fluorescence technology based on an elliptical
      monocapillary and a parallel polycapillary X-ray optics.
AB  - A total reflection X-ray fluorescence (TXRF) spectrometer based on an elliptical
      monocapillary X-ray lens (MXRL) and a parallel polycapillary X-ray lens (PPXRL)
      was designed. This TXRF instrument has micro focal spot, low divergence and high
      intensity of incident X-ray beam. The diameter of the focal spot of MXRL was 16.5
      um, and the divergence of the incident X-ray beam was 3.4 mrad. We applied this
      TXRF instrument to the micro analysis of a single-layer film containing Ni
      deposited on a Si substrate by metal vapor vacuum arc ion source.

PMID- 29653298
TI  - Voluntary health insurance in Nigeria: Effects on takers and non-takers.
AB  - Interventions aiming to simultaneously improve financial protection and quality
      of care may provide an important avenue towards universal health coverage. We
      estimate the effects of the introduction of the Kwara State Health Insurance
      program in Nigeria on not only the insured but also the uninsured. A subsidized
      voluntary low cost health insurance was offered by a private insurer as well as a
      quality upgrade in selected health care facilities. Using propensity score
      matching and panel data collected in 2009 and 2011 (n = 3509), we find that, for
      the insured, the program increased health care utilization (36 percent, p <
      0.000) and reduced out of pocket expenditure (63 percent, p < 0.000). However,
      the uninsured in the area with upgraded facilities did not increase their care
      utilization and even spent less on health care, which is problematic given that
      67 percent of the population in the treatment area did not take up the insurance.
      Our findings suggest that while voluntary health insurance combined with
      investments in health care supply can increase health care use and financial
      protection among those that take up the insurance, attention should be paid to
      potential unintended effects on the - typically sizeable- group of people who do
      not enroll in the insurance.

PMID- 29653300
TI  - Comparison of solvent extraction and extraction chromatography resin techniques
      for uranium isotopic characterization in high-level radioactive waste and barrier
      materials.
AB  - The development of Deep Geological Repositories (DGP) to the storage of high
      level radioactive waste (HLRW) is mainly focused in systems of multiple barriers
      based on the use of clays, and particularly bentonites, as natural and engineered
      barriers in nuclear waste isolation due to their remarkable properties. Due to
      the fact that uranium is the major component of HLRW, it is required to go in
      depth in the analysis of the chemistry of the reaction of this element within
      bentonites. The determination of uranium under the conditions of HLRW, including
      the analysis of silicate matrices before and after the uranium-bentonite
      reaction, was investigated. The performances of a state-of-the-art and widespread
      radiochemical method based on chromatographic UTEVA resins, and a well-known and
      traditional method based on solvent extraction with tri-n-butyl phosphate (TBP),
      for the analysis of uranium and thorium isotopes in solid matrices with high
      concentrations of uranium were analysed in detail. In the development of this
      comparison, both radiochemical approaches have an overall excellent performance
      in order to analyse uranium concentration in HLRW samples. However, due to the
      high uranium concentration in the samples, the chromatographic resin is not able
      to avoid completely the uranium contamination in the thorium fraction.

PMID- 29653301
TI  - The moderating role of resilience on the relationship between perceived stress
      and binge eating symptoms among young adult women.
AB  - OBJECTIVE: Adolescence and young adulthood are developmental periods during the
      life course that are sometimes associated with heightened stress and engagement
      in binge eating. Binge eating has been linked to psychiatric comorbidity, poorer
      physical health, and lower quality of life. However, less is known about
      protective factors that could buffer against binge eating behaviors. The current
      study examined the moderating role of resilience on the relationship between
      perceived stress and binge eating symptoms among emerging adult female college
      students. METHOD: Participants were 297 young adult women aged 18-25 years (Mage
      = 19.22, SD = 1.51; 52% self-identifying as a racial/ethnic minority) with Body
      Mass Index ranging from 15 to 66 (MBMI = 25.01, SD = 6.18). Women completed this
      cross-sectional study while they were attending universities in the Western or
      Southern United States. Participants provided demographic and height/weight
      information, and completed the following measures: Perceived Stress Scale, Binge
      Eating Scale, and Brief Resilience Scale. RESULTS: Higher perceived stress was
      significantly associated with more severe binge eating symptoms (b = 0.31; p <
      .01). In addition, higher resilience was associated with lower binge eating
      pathology (b = -0.20; p < .01). Moderation was supported as the relationship
      between perceived stress and binge eating symptoms varied by resilience level (b
      = -0.16; p < .01). CONCLUSIONS: Women who perceived higher stress were more
      likely to engage in binge eating relative to women experiencing low stress;
      however, resilience attenuated this association. Resilience could be targeted to
      reduce the negative effects of perceived stress on eating behaviors in young
      women.

PMID- 29653302
TI  - Jembrana disease virus Vif antagonizes the inhibition of bovine APOBEC3 proteins
      through ubiquitin-mediate protein degradation.
AB  - Viral infectivity factor (Vif) encoded by lentiviruses is essential for viral
      replication and escaping from antiviral activity of host defensive factors
      APOBEC3. Jembrana disease virus (JDV) causes an acute disease syndrome with
      approximately 20% case fatality rate in Bali cattle. However, the interplay
      mechanism between JDV Vif and Bos taurus APOBEC3 (btA3) is poorly understood. In
      this study, we determined that JDV Vif recruits ElonginB, ElonginC(ELOB/C), Cul2
      and RBX1 but without the need of CBF-beta to form E3 ubiquitin ligase and induces
      the degradation of btA3 proteins. Further investigation identified BC-box
      (T149LQ151) motif required for ELOB/C binding, Cul2 box (Y167xxxxV/X172) and a
      zinc-binding motif (H95-C113-H115-C133) required for Cul2 binding in JDV Vif. The
      precise mechanism of JDV Vif overcoming the antiviral activity of btA3 proteins
      is helpful for the application of the broad spectrum antiviral drug targeting
      conserved functional domains of various species Vif proteins in the future.

PMID- 29653303
TI  - Effect of nanomaterials on arsenic volatilization and extraction from flooded
      soils.
AB  - Herein, we utilize sequential extraction and high-throughput sequencing to
      investigate the effects of nanomaterial additives on As volatilization from
      flooded soils. We reveal that maximum volatilization is achieved in the fourth
      week and is followed by stabilization. The extent of volatilization decreased in
      the order of control > nano-zerovalent iron >40-nm hydroxyapatite > nano-Fe3O4 >
      20-nm hydroxyapatite > multilayer graphene oxide > high-quality graphene oxide.
      The most abundant forms of As in soil corresponded to As-Fe and Al oxides. In
      soil with low levels of As pollution, the contents of these species increased
      after treatment with graphene oxides but decreased after treatment with other
      nanomaterials, with an opposite trend observed for soil with high levels of As
      pollution. The addition of nanomaterials influenced the activity of soil enzymes,
      e.g., hydroxyapatites affected the activities of urease and alkaline phosphatase,
      whereas graphene oxides significantly impacted that of peroxidase (P < 0.05). The
      addition of nanomaterials (which can potentially inhibit microbial growth)
      affected As levels by influencing the amount of As volatilized from polluted
      soil. Moreover, As volatilization, enzyme activity, and As speciation were
      observed to be mutually correlated (e.g., volatilization was negatively
      correlated to peroxidase activity and the contents of amorphous crystalline
      hydrous oxides of As-Fe and Al).

PMID- 29653305
TI  - Differential bioaccumulation of mercury by zooplankton taxa in a mercury
      contaminated reservoir Guizhou China.
AB  - Mercury (Hg) contamination in aquatic systems remains a global concern with the
      biomagnification of methylmercury (MeHg) through primary consumers (zooplankton)
      to fish and humans. In this study, total mercury (THg) and MeHg concentrations
      were analyzed in zooplankton collected from Baihua reservoir (Guizhou Province,
      China). Our results demonstrated that THg and MeHg concentrations were strongly
      correlated to zooplankton community and biomass composition. The THg
      concentration was significantly higher in micro-zooplankton compared to meso
      zooplankton and macro-zooplankton, and MeHg concentration increased significantly
      as body size increased. Hg increases in zooplankton were influenced by the
      numbers of calanoid copepods and Daphnia present relative to phytoplankton and
      zooplankton biomass. Many zooplankton taxa in the three size-fractions were
      affected by THg exposure. The biomasses of Bosmina longirostris, Thermocyclops
      brevifurcatus, Asplanchna priodonta and Cyclops vicinus vicinus were positively
      correlated with Hg accumulation, while Daphnia hyalina, and Phyllodiaptomus
      tunguidus had a negative association. THg and MeHg bioaccumulation factors were
      correlated with phosphorus and total nitrogen concentration, zooplankton biomass,
      and chlorophyll-a concentration. Phosphorus loading was associated with increased
      THg and MeHg accumulation in the zooplankton highlighting biomagification with
      eutrophication. Chlorophyll-a levels were not correlated to THg and MeHg
      accumulation in zooplankton when phytoplankton densities were >107 cells L-1 and
      chlorophyll-a concentrations <9 MUgL-1. This finding contradicts the idea of MeHg
      biodilution with increased algae biomass. However, changes in the phytoplankton
      species and biomass altered the availability of food for zooplankton,
      particularly micro-zooplankton and macro-zooplankton. Ultimately, the
      bioaccumulation of MeHg and THg across lower trophic levels was based more on the
      availability of preferred food resources than on total biological productivity.

PMID- 29653306
TI  - Tissue-specific distribution and bioaccumulation potential of organophosphate
      flame retardants in crucian carp.
AB  - The concentrations, distributions, and bioaccumulation of nine organophosphate
      flame retardants (OPFRs) were investigated in both abiotic and biotic media,
      comprising river water, sediment, and crucian carp. The highest concentrations
      were observed in liver (6.22-18.1 ng/g ww), and the levels in muscle (4.23-7.75
      ng/g ww) and gonad (3.08-7.70 ng/g ww) were similar. In whole blood, tris(2
      butoxyethyl) phosphate (TBOEP; 31.1-256 ng/mL) accounted for 90% of the total
      OPFR concentration. Distributions of OPFRs differed between biotic and abiotic
      media, as tris(2-chloroethyl) phosphate (TCEP), tris(1-chloro-2-propyl) phosphate
      (TCIPP), and TBOEP were dominant in abiotic media, whereas triethyl phosphate
      (TEP), tri-n-butyl phosphate (TNBP), TCEP, and TBOEP dominated in crucian carp.
      The TNBP had remarkable accumulation potential among nine OPFRs, which the TNBP
      concentrations in muscle increased with increased total length and body weight.
      The higher perfusion rate of TNBP to female eggs were observed rather than to
      male gonads as the concentrations were higher in males than in females, while the
      opposite results were observed in gonad. Moreover, the concentration of TNBP in
      female muscle began to decrease near maximum growth as a sexually dimorphic
      difference in crucian carp. This is the first study to simultaneously investigate
      the fate of OPFRs in biotic and abiotic media and to show sex differences.

PMID- 29653307
TI  - Nitrogen concentration in moss compared with N load in precipitation and with
      total N deposition in Switzerland.
AB  - Intensification of farming and an increase in motorised traffic have led to
      elevated nitrogen (N) emissions and thus to eutrophication of the environment,
      which threatens the nutrient balance in ecosystems. Earlier studies have
      demonstrated the suitability of mosses as biomonitors for measuring N deposition
      by comparing the N concentration in moss with that in precipitation. In our study
      however, we extended the comparison to the dry deposition of gases (nitrogen
      dioxide, nitric acid, ammonia) and aerosols (nitrate, ammonium), which, together
      with the N in precipitation, represent the main contributions to total N
      deposition. The aim of including several N compounds was to see whether the
      correlation with the N concentration in moss could be improved. We determined
      total N input from the atmosphere to the ecosystem at 24 sites in Switzerland and
      compared this value to the N concentration in two moss species collected <1000 m
      from these sites. Including the gases and aerosols improved the correlation
      between the N concentration in moss and N deposition. Ammonia was found to be the
      most important of the additionally included compounds at these sites. Especially
      at sites with a relatively high ammonia concentration in the air, the inclusion
      of ammonia improved the correlation of the comparison. We also demonstrate that
      the particular moss species tested had no influence on the correlation between N
      in moss and total N deposition. Our data supports the suitability of mosses as
      biomonitors for estimating N input into ecosystems.

PMID- 29653304
TI  - A review of the pharmaceutical exposome in aquatic fauna.
AB  - Pharmaceuticals have been considered 'contaminants of emerging concern' for more
      than 20 years. In that time, many laboratory studies have sought to identify
      hazard and assess risk in the aquatic environment, whilst field studies have
      searched for targeted candidates and occurrence trends using advanced analytical
      techniques. However, a lack of a systematic approach to the detection and
      quantification of pharmaceuticals has provided a fragmented literature of
      serendipitous approaches. Evaluation of the extent of the risk for the plethora
      of human and veterinary pharmaceuticals available requires the reliable
      measurement of trace levels of contaminants across different environmental
      compartments (water, sediment, biota - of which biota has been largely
      neglected). The focus on pharmaceutical concentrations in surface waters and
      other exposure media have therefore limited both the characterisation of the
      exposome in aquatic wildlife and the understanding of cause and effect
      relationships. Here, we compile the current analytical approaches and available
      occurrence and accumulation data in biota to review the current state of research
      in the field. Our analysis provides evidence in support of the 'Matthew Effect'
      and raises critical questions about the use of targeted analyte lists for
      biomonitoring. We provide six recommendations to stimulate and improve future
      research avenues.

PMID- 29653308
TI  - Methodological evolution and frontiers of identifying, modeling and preventing
      secondary crashes on highways.
AB  - Secondary crashes (SCs) or crashes that occur within the boundaries of the impact
      area of prior, primary crashes are one of the incident types that frequently
      affect highway traffic operations and safety. Existing studies have made great
      efforts to explore the underlying mechanisms of SCs and relevant methodologies
      have been evolving over the last two decades concerning the identification,
      modeling, and prevention of these crashes. So far there is a lack of a detailed
      examination on the progress, lessons, and potential opportunities regarding
      existing achievements in SC-related studies. This paper provides a comprehensive
      investigation of the state-of-the-art approaches; examines their strengths and
      weaknesses; and provides guidance in exploiting new directions in SC-related
      research. It aims to support researchers and practitioners in understanding well
      established approaches so as to further explore the frontiers. Published studies
      focused on SCs since 1997 have been identified, reviewed, and summarized. Key
      issues concentrated on the following aspects are discussed: (i) static/dynamic
      approaches to identify SCs; (ii) parametric/non-parametric models to analyze SC
      risk, and (iii) deployable countermeasures to prevent SCs. Based on the examined
      issues, needs, and challenges, this paper further provides insights into
      potential opportunities such as: (a) fusing data from multiple sources for SC
      identification, (b) using advanced learning algorithms for real-time SC analysis,
      and (c) deploying connected vehicles for SC prevention in future research. This
      paper contributes to the research community by providing a one-stop reference for
      research on secondary crashes.

PMID- 29653309
TI  - Bioactive extracellular compounds produced by the dinoflagellate Alexandrium
      minutum are highly detrimental for oysters.
AB  - Blooms of the dinoflagellate Alexandrium spp., known as producers of paralytic
      shellfish toxins (PSTs), are regularly detected on the French coastline. PSTs
      accumulate into harvested shellfish species, such as the Pacific oyster
      Crassostrea gigas, and can cause strong disorders to consumers at high doses. The
      impacts of Alexandrium minutum on C. gigas have often been attributed to its
      production of PSTs without testing separately the effects of the bioactive
      extracellular compounds (BECs) with allelopathic, hemolytic, cytotoxic or
      ichthyotoxic properties, which can also be produced by these algae. The BECs,
      still uncharacterized, are excreted within the environment thereby impacting not
      only phytoplankton, zooplankton but also marine invertebrates and fishes, without
      implicating any PST. The aim of this work was to compare the effects of three
      strains of A. minutum producing either only PSTs, only BECs, or both PSTs and
      BECs, on the oyster C. gigas. Behavioral and physiological responses of oysters
      exposed during 4 days were monitored and showed contrasted behavioral and
      physiological responses in oysters supposedly depending on produced bioactive
      substances. The non-PST extracellular-compound-producing strain primarily
      strongly modified valve-activity behavior of C. gigas and induced hemocyte
      mobilization within the gills, whereas the PST-producing strain caused
      inflammatory responses within the digestive gland and disrupted the daily
      biological rhythm of valve activity behavior. BECs may therefore have a
      significant harmful effect on the gills, which is one of the first organ in
      contact with the extracellular substances released in the water by A. minutum.
      Conversely, the PSTs impact the digestive gland, where they are released and
      mainly accumulated, after degradation of algal cells during digestion process of
      bivalves. This study provides a better understanding of the toxicity of A.
      minutum on oyster and highlights the significant role of BECs in this toxicity
      calling for further chemical characterization of these substances.

PMID- 29653310
TI  - A self-template and self-activation co-coupling green strategy to synthesize high
      surface area ternary-doped hollow carbon microspheres for high performance
      supercapacitors.
AB  - Development of facile and cost-effective routes to achieve hierarchical porous
      and heteroatoms-doped carbon architectures is urgently needed for high
      performance supercapacitor application. In our study, ternary-doped (nitrogen,
      phosphorus and oxygen) hollow carbon microspheres (NPO-HCSs) are fabricated by
      one-step pyrolysis of single poly(cyclotriphosphazene-co-phloroglucinol) (PCPP)
      microsphere, which is generated through a facile polymerization between
      hexachlorocyclotriphosphazene and phloroglucinol at mild conditions. The whole
      preparation process is not used any additional template or activating agent. The
      obtained NPO-HCS-950 with average diameter of 580 nm and shell thickness of about
      80 nm have a high specific surface area (2390 m2 g-1), a large pore volume (1.35
      cm3 g-1), hierarchically interconnected pore texture, and uniform ternary
      heteroatom doping (O: 3.04 at%; N: 1.33 at% and P: 0.67 at%). As an electrode
      material for supercapacitors, the specific capacitance of the NPO-HCS-950 reaches
      253 F g-1 of 1 A g-1 and 176 F g-1 at 20 A g-1, revealing superior rate
      performance. The capacity retention after 10,000 consecutive charge-discharge
      cycles at 20 A g-1 is up to 98.9%, demonstrating excellent cycling stability.
      Moreover, the assembled symmetric supercapacitor using NPO-HCS-950 exhibits a
      relatively high energy density of 17.6 W h kg-1 at a power density of 800 W kg-1.
      Thus, a promising electrode material for high-performance supercapacitors is
      obtained through a facile, green and scalable synthesis route.

PMID- 29653311
TI  - As(V) removal capacity of FeCu bimetallic nanoparticles in aqueous solutions: The
      influence of Cu content and morphologic changes in bimetallic nanoparticles.
AB  - In this study, bimetallic nanoparticles (BMNPs) with different mass ratios of Cu
      and Fe were evaluated. The influence of the morphology on the removal of
      pollutants was explored through theoretical and experimental studies, which
      revealed the best structure for removing arsenate (As(V)) in aqueous systems. To
      evidence the surface characteristics and differences among BMNPs with different
      mass proportions of Fe and Cu, several characterization techniques were used.
      Microscopy techniques and molecular dynamics simulations were applied to
      determine the differences in morphology and structure. In addition, X-ray
      diffraction (XRD) was used to determine the presence of various oxides. Finally,
      the magnetization response was evaluated, revealing differences among the
      materials. Our cumulative data show that BMNPs with low amounts of Cu
      (Fe0.9Cu0.1) had a non-uniform core-shell structure with agglomerate-type chains
      of magnetite, whereas a Janus-like structure was observed in BMNPs with high
      amounts of Cu (Fe0.5Cu0.5). However, a non-uniform core-shell structure
      (Fe0.9Cu0.1) facilitated electron transfer among Fe, Cu and As, which increased
      the adsorption rate (k), capacity (qe) and intensity (n). The mechanism of As
      removal was also explored in a comparative study of the phase and morphology of
      BMNPs pre- and post-sorption.

PMID- 29653312
TI  - Improved chemo-photothermal therapy of hepatocellular carcinoma using chitosan
      coated gold nanoparticles.
AB  - A green method was used for producing gold nanoparticles (Au NPs) using chitosan
      as a natural cationic, biodegradable and biocompatible polymer. In this method,
      chitosan acts as a reducing and stabilizing agent for the synthesis of Au NPs.
      Different concentrations of chitosan solutions (0.01%, 0.05%, 0.1%, 0.2%, 0.5%
      and 1%) were applied. In an attempt to mitigate the side effects of anti-cancer
      drug, 5-fluorouracil (5-FU), through reducing drug doses in photothermal therapy,
      the formed positively-charged chitosan-wrapped Au NPs were used as a drug
      delivery system for negatively charged 5-FU to hepatocellular carcinoma cells
      (HepG2). Au NPs as well as 5-FU@Au nanocomposites were characterized with UV-VIS
      spectroscopy, particle size, zeta potential, Fourier transform infrared
      spectroscopy (FTIR), transmission electron microscopy (TEM) and High-Performance
      Liquid Chromatography (HPLC). The chitosan concentration was shown to be an
      important parameter for optimizing the dispersion of Au NPs and 5-FU@Au
      nanocomposites over long time. This stability offers the 5-FU@Au nanocomposites
      as good candidate for cancer treatment with reduced drug doses in photothermal
      therapy. A 72% loading-efficiency of 5-FU was obtained. Cytotoxic assay was
      carried out on HepG2 cell line and it reveals the effectiveness of 5-FU@Au
      nanocomposites in the presence and absence of laser irradiation compared with the
      free 5-FU. The cytotoxicity effect of free 5-FU and 5-FU@AuNPs nanocomposites was
      studied, and it was found that the concentration of 5-FU@Au nanocomposites
      required to attain 50% of inhibition growth rate was lower than that of free 5-FU
      in absence of laser radiation and was much lower in presence of laser radiation.

PMID- 29653313
TI  - Hydroalcoholic extracts of Myracrodruon urundeuva All. and Qualea grandiflora
      Mart. leaves on Streptococcus mutans biofilm and tooth demineralization.
AB  - OBJECTIVES: This study evaluated the effect of the hydroalcoholic extracts of
      Myracrodruon urundeuva All. and Qualea grandiflora Mart. leaves (alone or
      combined) on the viability of Streptococcus mutans biofilm and on the prevention
      of enamel demineralization. METHODS: Strain of S. mutans (ATCC 21175) was
      reactivated in BHI broth. Minimum inhibitory concentration, minimum bactericidal
      concentration, minimum inhibition biofilm concentration and minimum eradication
      biofilm concentration were determined in order to choose the concentrations to be
      tested under biofilm model. S. mutans biofilm (5 * 105 CFU/ml) was produced on
      bovine enamel, using McBain saliva under 0.2% sucrose exposure, for 3 days. The
      biofilm was daily treated with the extracts for 1 min. The biofilm viability was
      tested by fluorescence and the enamel demineralization was measured using TMR.
      RESULTS: Myracrodruon urundeuva All. (Isolated or combined) at the
      concentrationsc >=0.625 mg/ml was able to reduce bacteria viability, while Qualea
      Grandflora Mart. alone had antimicrobial effect at 5 mg/ml only (p < 0.05). On
      the other hand, none of the extracts were able to reduce enamel demineralization.
      CONCLUSIONS: The hydroalcoholic extracts of Myracrodruon urundeuva All. and
      Qualea grandiflora Mart. leaves (isolated or combined) have antimicrobial action;
      however, they do not prevent enamel caries under S. mutans biofilm model.

PMID- 29653314
TI  - Hemifacial microsomia (oculo-auriculo-vertebral spectrum) in an individual from
      the Teramo Sant'Anna archaeological site (7th-12th centuries of the Common Era,
      Italy).
AB  - BACKGROUND: This study is based in an analysis of the skeletal remains of an
      adult male from the Teramo Sant'Anna archaeological site (7th-12th centuries of
      the Common Era, Teramo, Italy). RESULTS AND DISCUSSION: The individual shows
      distinct abnormalities that principally involve asymmetric hypoplasia and
      dysmorphogenesis of the facial skeleton. The combination of these findings and
      the absence of abnormalities of the spine strongly suggest diagnosis of the
      congenital malformation known as hemifacial microsomia. This very heterogeneous
      syndrome affects primarily aural, ocular, oral and mandibular development.
      Despite the lack of clinical information and the absence of soft tissue, it was
      possible to perform a differential diagnosis for this palaeopathological case.
      Mastication was probably altered considering that the mandible is extremely
      asymmetric and lacks true condyles. The temporomandibular joints are present, but
      the right one is hypoplastic and abnormal in shape. There is evidence of
      bilateral dislocation, and the facial muscles are hypertrophic. CONCLUSIONS: This
      case represents an important contribution to the palaeopathological literature
      because this is an uncommon condition that has not been widely documented in
      ancient skeletal remains.

PMID- 29653315
TI  - EEG-based neurophysiological indicators of hallucinations in Alzheimer's disease:
      Comparison with dementia with Lewy bodies.
AB  - We studied neurophysiological indicators of hallucinations in Alzheimer's disease
      patients with hallucinations (ADhall+), and compared them with nonhallucinating
      AD (ADhall-) and dementia with Lewy bodies (DLBhall+) patients. Thirty-six
      matched ADhall+ and 108 ADhall- and 29 DLBhall+ patients were selected from the
      Amsterdam Dementia Cohort. Electroencephalography (EEG) spectral and functional
      connectivity (FC) analyses (phase lag index) were performed. Quantitative and
      visual EEG measures were combined in a random forest algorithm to determine which
      EEG-based variable(s) play a role in hallucinations. ADhall+ patients showed
      lower peak frequency (7.26 vs. 7.94 Hz, p < 0.01), alpha2-and beta-power, and
      alpha2-FC but higher delta-power compared to ADhall-. ADhall+ showed lower delta
      power, higher beta-power, and alpha1-FC than DLBhall+ but did not differ in peak
      frequency (7.26 vs. 6.95 Hz), theta- or alpha-power. ADhall+ patients could be
      differentiated from ADhall- and DLBhall+ with a weighted accuracy of 71% with
      alpha1-power and 100% with beta-FC, the 2 most differentiating features. In sum,
      EEG slowing and decrease in alpha1-and beta-band activity form potential
      neurophysiological indicators of underlying cholinergic deficiency in ADhall+ and
      DLBhall+.

PMID- 29653317
TI  - Increased torsional stability by a novel femoral neck locking plate. The role of
      plate design and pin configuration in a synthetic bone block model.
AB  - BACKGROUND: In undisplaced femoral neck fractures, internal fixation remains the
      main treatment, with mechanical failure as a frequent complication. As torsional
      stable fixation promotes femoral neck fracture healing, the Hansson Pinloc(r)
      System with a plate interlocking pins, was developed from the original hook pins.
      Since its effect on torsional stability is undocumented, the novel implant was
      compared with the original configurations. METHODS: Forty-two proximal femur
      models custom made of two blocks of polyurethane foam were tested. The medial
      block simulated the cancellous head, while the lateral was laminated with a glass
      fiber filled epoxy sheet simulating trochanteric cortical bone. Two hollow metal
      cylinders with a circumferential ball bearing in between mimicked the neck, with
      a perpendicular fracture in the middle. Fractures were fixated by two or three
      independent pins or by five configurations involving the interlocking plate (two
      pins with an optional peg in a small plate, or three pins in a small, medium or
      large plate). Six torsional tests were performed on each configuration to
      calculate torsional stiffness, torque at failure and failure energy. FINDINGS:
      The novel configurations improved parameters up to an average of 12.0
      (stiffness), 19.3 (torque) and 19.9 (energy) times higher than the original two
      pins (P < 0.001). The plate, its size and its triangular configuration improved
      all parameters (P = 0.03), the plate being most effective, also preventing
      permanent failure (P < 0.001). INTERPRETATION: The novel plate design with its
      pin configuration enhanced torsional stability. To reveal clinical relevance a
      clinical study is planned.

PMID- 29653316
TI  - Clinical variability and onset age modifiers in an extended Belgian GRN founder
      family.
AB  - We previously reported a granulin (GRN) null mutation, originating from a common
      founder, in multiple Belgian families with frontotemporal dementia. Here, we used
      data of a 10-year follow-up study to describe in detail the clinical
      heterogeneity observed in this extended founder pedigree. We identified 85
      patients and 40 unaffected mutation carriers, belonging to 29 branches of the
      founder pedigree. Most patients (74.4%) were diagnosed with frontotemporal
      dementia, while others had a clinical diagnosis of unspecified dementia,
      Alzheimer's dementia or Parkinson's disease. The observed clinical heterogeneity
      can guide clinical diagnosis, genetic testing, and counseling of mutation
      carriers. Onset of initial symptomatology is highly variable, ranging from age 45
      to 80 years. Analysis of known modifiers, suggested effects of GRN rs5848,
      microtubule-associated protein tau H1/H2, and chromosome 9 open reading frame 72
      G4C2 repeat length on onset age but explained only a minor fraction of the
      variability. Contrary, the extended GRN founder family is a valuable source for
      identifying other onset age modifiers based on exome or genome sequences. These
      modifiers might be interesting targets for developing disease-modifying
      therapies.

PMID- 29653318
TI  - Work of non-elastic deformation against the deformation ratio of the Subcompact
      Car Class using the variable correlation method.
AB  - The presented study considers a Subcompact Car Class in a new non-linear method
      utilising the work W of car deformation defined as an algebraic function of
      deformation ratio Cs. In order to develop the experimental data, the method of
      variable correlation is utilised. Data from the NHTSA (National Highway Traffic
      Safety Administration) database comprising numerous frontal crash tests are used
      for the determination of mathematical model parameters. In the non-linear method
      used up until now, the so-called energetic approach, collisions are treated as
      non-elastic. The velocity threshold that defines the elastic collision was set to
      be 11km/h. Such an approach, which is very simplified, determines the linear
      dependence of energy lost during deformation on deformation coefficient Cs. This
      coefficient is calculated as a mean value, taking into account the weights of
      deformation points C1-C6. In this paper, the authors propose a more precise non
      linear method in order to determine the work of deformation, and have used the
      more complex form of deformation coefficient.

PMID- 29653319
TI  - Analysis of fatal accidents with tractors in the Centre of Portugal: Ten years
      analysis.
AB  - Tractors have been described as one of the deadliest farming implements
      concerning agricultural activity. In Portugal, the scientific investigations
      about this problem are practically non-existent, with only statistical studies
      performed by entities related to road traffic safety, not in accordance to the
      study now performed, pinpointing the possibility of an underreporting of these
      accidents. This work aims to characterize the fatal tractor accidents in
      Portugal, autopsied at the Forensic Pathology Department of the Centre Branch of
      the National Institute of Legal Medicine and Forensic Sciences of Portugal,
      analysing several variables: gender, age, occupation, survival time, the victim
      position in the tractor, cause of death, toxicological and histological exams,
      year/month/day of the week, type of agricultural machine, existence of rollover
      protective structures (ROPS), type of accident, ground conditions, circumstantial
      information and geographic distribution of the accidents. All the autopsies
      between 2005 and 2014 were analysed. The victim profile corresponded to a man
      (89.5%), between 61 and 70 years old (33.3%), retired (43.9%), being the tractor
      driver (45.6%). In most of the cases, death occurred in less than 24h after the
      accident. These fatalities arose mainly in May and October. Rollover in sloping
      land was the most common type of accident, and cranioencephalic, thoracic and
      abdominal traumatic injuries were the main cause of death. In 16.2% of the cases,
      blood alcohol concentration was above the lower limit established in our road
      traffic law (<0.5g/L). There was lack information about the use of ROPS (95.9%),
      and even when existent, the protections were not used or were incorrectly used.
      This is the first national study involving the description of the forensic
      achievements in each autopsy related to tractor accidents, and the corresponding
      circumstances that contributed to the death. Many barriers remain about this
      matter, but the Portuguese government begin to design several laws to prevent
      this type of accidents. Future investigations should be performed to understand
      the real dimension of tractor accidents in Portugal, and to comprehend the
      efficiency of laws implemented by the government.

PMID- 29653320
TI  - Is the "flipped" pedagogical model the answer to the challenges of rural nursing
      education?: A discussion paper?
AB  - Rural Australian health services face significant challenges such as aging
      populations, access and retention of services and health practitioners as well as
      difficulties with staff training due to geographic isolation. Educational
      pedagogy, through a 'flipped' or 'flipped' classroom method has become popular in
      nursing literature whereby discussion surrounding its effectiveness, ability to
      increase performance, address learning outcomes and resolve the education
      clinical practice divide is currently being explored. Several reviews that look
      specifically at the validity and implementation of the flipped classroom pedagogy
      into nursing education demonstrate a need for further scientific research.
      Current literature examines the in-class on campus implementation of the
      methodology but rarely does it consider the advantages or ways of implementing
      such a method in a rural off campus nursing learning environment. The use of
      technology is not the solution unless supported by interaction to develop
      practical situational skills. The authors consider advantages and disadvantages
      and identify central problems for the effective implementation of 'flipped' in
      off-campus rural nursing education.

PMID- 29653321
TI  - Neurodevelopmental comorbidities and seizure control 24 months after a first
      unprovoked seizure in children.
AB  - PURPOSE: To follow children with newly diagnosed unprovoked seizures to determine
      (1) whether the prevalence of neurodevelopmental comorbidities and cerebral palsy
      (CP) changed after the initial seizure, and (2) the association between studied
      comorbidities and seizures 13-24 months after seizure onset or initiation of
      treatment. METHODS: Analyses were based on 750 children (28 days-18 years) with a
      first unprovoked seizure (index) included in a population-based Incidence
      Registry in Stockholm between 2001 and 2006. The children were followed for two
      years and their medical records were examined for a priori defined
      neurodevelopmental/psychiatric comorbidities and CP and seizure frequency.
      Baseline information was collected from medical records from before, and up to
      six months after, the index seizure. Odds ratios (OR) of repeated seizures 13-24
      months after the first seizure or after initiation of anti-epileptic drug
      treatment was calculated by logistic regression and adjusted for age and sex.
      RESULTS: At baseline, 32% of the children had neurodevelopmental/psychiatric
      comorbidities or CP compared to 35%, 24 months later. Children with such
      comorbidities more often experienced seizures 13-24 months after the index
      seizure (OR 2.87, CI 2.07-3.99) with the highest OR in those with CP or attention
      deficit hyperactivity disorder (ADHD). Children diagnosed at age <1 year
      exhibited the highest prevalence of comorbidities as well as OR for repeated
      seizures. A combination of young age and comorbidity was associated with an OR
      for repeated seizures of 5.12 (CI 3.03-8.65). Among the children without
      comorbidities 76% were seizure free 13-24 months after the index seizure or after
      initiation of AED treatment compared to 53% of children with comorbidities.
      CONCLUSIONS: This study indicates that neurodevelopmental comorbidities and CP in
      children with epilepsy tend to be present already at seizure onset and that such
      comorbidities are strong indicators of poor outcome regarding seizure control
      with or without treatment.

PMID- 29653322
TI  - Role and application of iron in water treatment for nitrogen removal: A review.
AB  - It is crucial to have a review on the role of iron in water treatment for the
      guidance towards the selection of appropriate processes, content of iron, and
      application conditions, as there are few reviews available at present and the
      systematic information is lacking for both researchers and engineers. The
      objectives of this review are to summarize the state of arts with respect to iron
      applied in nitrogen removal, discuss chemical and biological or bio-chemical
      combined nitrogen removal pathways and processes coupled with iron, and to reveal
      reaction mechanisms as well as providing references or even solutions to
      pertinent the practical engineering application of nitrate removal coupling with
      iron. The following information have been summarized and discussed in details:
      (1) iron based materials with varieties of preparations and forms, (2) major
      coupling ways of nitrogen removal methods or processes with iron application, (3)
      chemical reaction equations about a variety of chemical and biological or bio
      chemical combined processes and the main mechanisms. In addition, challenges
      and/or drawbacks during the nitrogen removal processes will also be discussed in
      this paper, which is aimed to seek better practical engineering applications of
      nitrate removal coupling with iron.

PMID- 29653323
TI  - Potential risk of coupling products between tetrahalobisphenol A and humic acid
      prepared via oxidation with a biomimetic catalyst.
AB  - Tetrahalobisphenol A (TXPBAs, X = Br or Cl), TBBPA and TCBPA, which are widely
      used as flame retardants, ultimately disposed of in landfills. In landfills,
      enzymatically oxidized TXBPAs can be covalently incorporated into humic acids
      (HAs) to form coupling products (HA-TXBPAs). In the present study, HA-TXBPAs were
      prepared by catalytic oxidation with iron(III)-phthalocyanine-tetrasulfate as a
      model of oxidative enzymes. The stability of HA-TXBPAs was evaluated by
      incubating them under physicochemical conditions of landfills (pH 9 and 50 
      degrees C). For HA-TBBPA, 18-26% of TBBPA was released from HA-TBBPA, due to the
      acid dissociation of the loosely bound TBBPA. However, no additional release was
      observed, even after 30 days, indicating that 74-82% of the TBBPA was
      incorporated into the HA. For HA-TCBPA, 3-4% of TCBPA and a major byproduct, 4-(2
      hydroxyisopropyl)-2,6-dichlorophenol, was found to be loosely incorporated into
      HA. For both TBBPA and TCBPA, covalently bound organo-halogens were not released
      during the 30 days of incubation. Inhibition of the growth of Chlamydomonas
      reinhardtii was indicated when trace levels of TXBPAs (approximately 0.1 MUM)
      were present. These results suggest that HA-TXBPAs contain not only covalently
      incorporated TXBPAs but also loosely bound TXBPAs and halophenols. The latter in
      HA-TXBPAs have the potential to leach from landfills and affect aquatic
      ecosystems.

PMID- 29653324
TI  - Phytoremediation of mine tailings with Atriplex halimus and organic/inorganic
      amendments: A five-year field case study.
AB  - Mine tailings have adverse chemical and physical conditions, including high
      concentrations of metals and salts, low organic matter content, and unbalanced
      rates of nutrients which limit the development of vegetation. A large scale field
      experiment was conducted to reclaim a tailing pond by triggering the growth of
      native species by spontaneous colonization by tilling (TL) the tailing pond
      surface and using marble waste (CaCO3; MW), pig slurry (PS) and their combination
      (MW + PS) as soil amendments. Soil physicochemical properties and water and DTPA
      extractable metal concentrations of bulk and rhizosphere soils were analyzed
      after five year from the application of the treatments. In addition, plants of
      Atriplex halimus from each treatment were collected and metals in roots, leaves
      and stems analyzed. Before amendments application, the studied pond showed a
      neutral pH, high salinity and a moderate organic carbon content. After five
      years, the pH value was significantly increased only in MW plot. The results
      showed significant increases of DTPA-extractable Zn in MW and MW + PS plots, Pb
      in all treatments except MW plot, Cd only in PS plot, and Cu only in MW + PS
      plot. A. halimus was the most dominant species, growing spontaneously in all
      plots, with lower vegetation cover in CT and MW plots, 6% and 2% respectively.
      Application of MW increased leaf Pb accumulation by 2.5-fold and Cd by 55%, when
      compared to the CT. The high initial salinity and probable substitution of metals
      by Ca2+ on exchangeable surfaces of soil particles may be the reasons for higher
      uptake of metals in MW plot when compared to the other plots. Although this plant
      is widely utilized in contaminated sites for phytostabilization purposes, it may
      absorb and translocate high concentrations of metals to the aboveground tissues
      in saline contaminated sites.

PMID- 29653325
TI  - Photocatalytic degradation of oilfield produced water using graphitic carbon
      nitride embedded in electrospun polyacrylonitrile nanofibers.
AB  - Separation and purification of oilfield produced water (OPW) is a major
      environmental challenge due to the co-production of the OPW during petroleum
      exploration and production operations. Effective capture of oil contaminant and
      its in-situ photodegradation is one of the promising methods to purify the OPW.
      Based on the photocatalytic capability of graphitic carbon nitride (GCN) which
      was recently rediscovered, photodegradation capability of GCN for OPW was
      investigated in this study. GCN was synthesized by calcination of urea and
      further exfoliated into nanosheets. The GCNs were incorporated into
      polyacrylonitrile nanofibers using electrospinning, which gave a liquid-permeable
      self-supporting photocatalytic nanofiber mat that can be handled by hand. The
      photocatalytic nanofiber demonstrated 85.4% degradation of OPW under visible
      light irradiation, and improved the degradation to 96.6% under UV light.
      Effective photodegradation of the photocatalytic nanofiber for OPW originates
      from synergetic effects of oil adsorption by PAN nanofibers and oil
      photodegradation by GCNs. This study provides an insight for industrial
      application on purification of OPW through photocatalytic degradation under solar
      irradiation.

PMID- 29653326
TI  - Biodegradation-mediated alterations in acute toxicity of water-accommodated
      fraction and single crude oil components in cold seawater.
AB  - Hydrocarbon biodegradation may be slower in cold Arctic than in temperate
      seawater, and this will affect the toxicity time window of the hydrocarbons. In
      this study, the acute toxicities of water-soluble phases of 1,3
      dimethylnaphthalene, phenanthrene, fluoranthene, and low energy water
      accommodated fractions (LE-WAFs) of an evaporated (200  degrees C+) crude oil,
      were screened by a Microtox bioassay during biodegradation in cold seawater (4-5 
      degrees C). The water-solubility of fluoranthene was too low to provoke a toxic
      response at any time, whereas the toxicity of 1,3-dimethylnaphthalene and
      phenanthrene decreased over time in relation to biotransformation of these
      compounds. In LE-WAFs, the Microtox EC50 was associated with biodegradation of
      the predominant hydrocarbons (naphthalenes, 2- to 3-ring PAH), as well as with
      phenol degradation products. The acute toxicities of single hydrocarbons and LE
      WAFs persisted for a longer period in the cold seawater than previously shown at
      higher seawater temperatures. These results suggest implications for fate and
      effects assessment of hydrocarbons after oil spills in cold environments, like
      the Arctic. However, further biodegradation studies using Arctic seawater and
      relevant species for toxicity testing are needed for confirmation.

PMID- 29653327
TI  - Zn, Ni, Mn, Cr, Pb and Cu in soil-tea ecosystem: The concentrations, spatial
      relationship and potential control.
AB  - Excessive accumulation of heavy metals in tea has certain health risk to the
      consumers. To discuss the spatial relationship between heavy metals in tea leaves
      and soil in a county scale, 74 samples of tea leaves and corresponding subsoil
      (15-30 cm) were collected in the tea plantations of Lishui, Nanjing, China. The
      total Zn, Ni, Mn, Cr, Pb and Cu in both tea leaves and soil samples, as well as
      pH value in soil were analyzed. The results of regression showed that the Mn and
      Cr in tea leaves were increased when the Mn and Cr in soil were at high levels,
      and higher pH decreased Zn, Ni, Mn and Cu contents in tea leaves. Moreover,
      distance to village and metal industry had negative impacts on the Mn level in
      soil. It is necessary to control the pH of soil in tea plantations which are
      close to villages or metal industries, as well as, to search more appropriate
      areas, where are far away from villages or metal industries, to plant tea should
      be taken into consideration. In addition, 17.57% of the samples have higher
      concentration of Pb than the maximum limits was found in tea plantation of
      Lishui. Heavy metals (Cr) standards regarding leafy vegetables is used for
      reference in this study, as there are no maximum levels of contaminants (MLC) in
      tea. It is significant to construct a targeted standard of heavy metals contents
      that could applicable throughout the world for reduce the health risks to the
      consumers.

PMID- 29653329
TI  - Multivariate relationships between microbial communities and environmental
      variables during co-composting of sewage sludge and agricultural waste in the
      presence of PVP-AgNPs.
AB  - This study evaluated the contributions of environmental variables to the
      variations in bacterial 16S rDNA, nitrifying and denitrifying genes abundances
      during composting in the presence of polyvinylpyrrolidone coated silver
      nanoparticles (PVP-AgNPs). Manual forward selection in redundancy analysis (RDA)
      indicated that the variation in 16S rDNA was significantly explained by NO3--N,
      while nitrifying genes were significantly related with pH, and denitrifying genes
      were driven by NO3--N and TN. Partial RDA further revealed that NO3--N solely
      explained 28.8% of the variation in 16S rDNA abundance, and pH accounted for
      61.8% of the variation in nitrifying genes. NO3--N and TN accounted for 34.2% and
      9.2% of denitrifying genes variation, respectively. The RDA triplots showed that
      different genes shared different relationships with environmental parameters.
      Based on these findings, a composting with high efficiency and quality may be
      conducted in the future work by adjusting the significant environmental
      variables.

PMID- 29653328
TI  - A pragmatic study on efficacy, tolerability and long term acceptance of ketogenic
      diet therapy in 74 South Indian children with pharmacoresistant epilepsy.
AB  - PURPOSE: Significant challenges exist for Ketogenic Diet (KD) programs in many
      populations, mainly due to the variations in local dietary preferences. Here we
      report a single center experience of KD therapy in a cohort of South Indian
      children with pharmaco-resistant epilepsies. METHODS: Children aged 0-18 years,
      enrolled in the KD program for pharmacoresistant epilepsies of Amrita institute
      of Medical Sciences, Kochi, Kerala, India (2010 - 2015) were included in this
      pragmatic study. Diet efficacy was evaluated according to reduction in seizure
      frequency and in the number of antiepileptic drugs (AED). Duration of retention,
      reasons for discontinuation and the rate of adverse events were used for
      assessing KD tolerability. RESULTS: Seventy four children were enrolled in the KD
      program. Four children could not complete the initiation process. Median age at
      KD initiation was 4.2years. 53 children had developmental delay. 89% were on 3 or
      more AEDs. Baseline seizure frequency was >5/day in 52 children. KD was continued
      for a median duration of 10.43 months. At the last contact, 59.4% reported
      seizure reduction of more than 50%. More than 90% reduction was noted in 25
      children (33.7%). 6(8.1%) of them became completely seizure free. Four children
      expired during the study period and four children reported major adverse events
      necessitating KD withdrawal. Main reasons for discontinuation of KD were poor
      compliance, lack of response to diet and relapse of seizures. CONCLUSION: KD may
      be a safe and effective option for children with pharmacoresistant epilepsies
      even while on a traditional carbohydrate rich South Indian diet.

PMID- 29653330
TI  - Response of greenhouse gas emissions and microbial community dynamics to
      temperature variation during partial nitrification.
AB  - This study investigated the greenhouse gas emission characteristics and microbial
      community dynamics with the variation of temperature during partial
      nitrification. Low temperature weakened nitrite accumulation, and partial
      nitrification would shift to complete nitrification easily at 15  degrees C.
      Based on CO2 equivalents (CO2-eq), partial nitrification process released 2.7 g
      of greenhouse gases per gMLSS per cycle, and N2O accounted for more than 98% of
      the total CO2-eq emission. The total CO2-eq emission amount at 35  degrees C was
      45.6% and 153.4% higher than that at 25  degrees C and 15  degrees C,
      respectively. During partial nitrification, the microbial community diversity
      greatly declined compared with seed sludge. However, the diversity was enhanced
      at low temperature. The abundance of Betaproteobacteria at class level increased
      greatly during partial nitrification. Proteobacteria abundance declined while
      Nitrospira raised at low temperature. The nosZ community abundance was not
      affected by temperature, although N2O emission was varied with the operating
      temperature.

PMID- 29653331
TI  - Enhanced hydrolysis of mechanically pretreated cellulose in water/CO2 system.
AB  - The aim of this work was to study promotion of ball milling and CO2 assistance on
      cellulose hydrolysis kinetics in water medium. Kinetic behaviors were analyzed
      based on first-order and shrinking core models. The results showed that cellulose
      hydrolysis is enhanced by ball milling and CO2 assistance. Ball milling reduced
      crystallinity and particle size of cellulose, resulting in high cellulose
      conversion, while hydrolysis promoted by CO2 assistance was weaker. Double-layer
      hydrolysis was observed for ball-milled cellulose, and rate constant in active
      layer is higher. Based on double-layer shrinking core model (DL-SCM), activation
      energy of cellulose conversion decreased from 73.6 to 39.8 kJ/mol when ball
      milling and CO2 assistance were applied. Hydrolysis active layer was about 0.9
      MUm, representing activated thickness of ball-milled cellulose. Hydrolysis
      promotion by crystallinity and particle size reduction was distinguished via DL
      SCM, and crystal evolution possesses greater improvement than particle size
      decrease on hydrolysis of ball-milled cellulose.

PMID- 29653332
TI  - Enhancing microalgae biofilm formation and growth by fabricating microgrooves
      onto the substrate surface.
AB  - Attachment of cells to substrate surface is the premise for biofilm formation. To
      shelter microalgae cells from fluid shear stress and offer larger areas for
      microalgae attachment, the inerratic microgrooves, which can act as anchor points
      that offer larger areas for microalgae attachment and induce vortex to protect
      cells from hydraulic shear stress, were designed and fabricated into substrate
      surface. The results indicated that the shear stress on the surface with V
      grooves was weaker than that on the surface with U-grooves, and 45 degrees  V
      grooves with the width of 200 MUm were benefit for cells attachment. The initial
      attachment time was shortened to 50 min under the hydraulic shear stress of 0.02
      Pa compared to that of 135 min on the surface without microgrooves. Subsequently,
      the biofilm biomass concentration on the surface with 45 degrees  V-grooves
      increased by 14.29% to 165.84 g m-2 compared with that on flat substrates.

PMID- 29653333
TI  - Mathematical model to appraise the inhibitory effect of phenolic compounds
      derived from lignin for biobutanol production.
AB  - This study aimed to establish a mathematical modeling to evaluate the inhibitory
      effect of phenolic derivatives on acetone-butanol-ethanol (ABE) fermentation by
      Clostridium saccharoperbutylacetonicum N1-4. Vanillin, 4-hydroxybenzoic acid, and
      syringaldehyde were selected to represent guaiacyl, hydroxyphenyl, and syringyl
      phenols, respectively, to be examined in a series of fed-batch experiments.
      Results show the presence of phenolic derivatives blocked the pathway of the
      assimilation of organic acids and reduced cell growth and glucose utilization.
      The inhibition model projected that the levels of 0.13, 0.14, and 0.04 g L-1 for
      vanillin, 4-hydroxybenzoic acid, and syringaldehyde, respectively, resulted in
      25% inhibition of butanol production, whereas 100% inhibition was predicted at
      the levels of 4.94, 4.37, and 4.20 g L-1 for vanillin, 4-hydroxybenzoic acid, and
      syringaldehyde, respectively. Syringaldehyde was more toxic than the other two
      compounds. The established model described that the phenolic compounds derived
      from different phenyl propane monomers of lignin severely obstructed biobutanol
      production.

PMID- 29653334
TI  - Evaluation of the mass transfer effects on delignification kinetics of
      atmospheric acetic acid fractionation of sugarcane bagasse with a shrinking-layer
      model.
AB  - A shrinking-layer model by modification of classical shrinking-core model was
      developed based on cell wall multi-layered structure for delignification of
      sugarcane bagasse with sulfuric acid (SA) catalyzed atmospheric acetic acid (AA)
      fractionation. The general model for overall rate of delignification was obtained
      and further employed to evaluate the mass transfer effects on delignification. It
      was found that the external diffusion could be neglected under the studied
      fractionation conditions, while the internal diffusion appeared to play an
      important role. The effective diffusion coefficient for lignin within the biomass
      was estimated as 6.7 * 10-14-1.6 * 10-12 m2/s depending on temperature, solid
      content in the system and molecular weight of lignin. However, surface reaction
      also seems to be a limiting step to the overall rate of delignification. At the
      early stage of delignification, both internal diffusion and reaction were
      controlling steps, while at the late stage reaction seems to be the controlling
      step.

PMID- 29653335
TI  - Influence of torrefaction with Mg-based additives on the pyrolysis of cotton
      stalk.
AB  - The study presented an approach to introduce Mg-based additives into cotton stalk
      for strengthening deoxygenation effect during torrefaction. Then catalytic
      pyrolysis of torrefied feedstock with Mg-based additives residue as catalyst was
      performed at 550  degrees C for 10 min in a fixed-bed reactor. The effects of
      torrefaction temperature (200, 230, 260, 290, 320, 350  degrees C), type of Mg
      based additive (MgO and MgO-K2CO3), mass ratio of additive to biomass (0.5, 1 and
      2) on pyrolysis were investigated. The results indicated that yields of bio-char
      and bio-oil significantly increased and decreased with torrefaction temperature
      rising to 350  degrees C. MgO inhibited pyrolysis bio-char yield increase with
      torrefaction severity. MgO-K2CO3 increased H2 yield a lot from 1.39 to 3.67
      mmol/g. It also effectively improved the aromatic hydrocarbons in bio-oil and the
      reduction of acids. A maximum aromatic hydrocarbons yield of 16.05% was obtained
      with MgO-K2CO3 (the mass ratio of 0.5:1) at torrefaction temperature of 320 
      degrees C.

PMID- 29653336
TI  - Efficient degradation of lignin in raw wood via pretreatment with heteropoly
      acids in gamma-valerolactone/water.
AB  - The aim of this work was to study the degradation of lignin in raw wood via
      pretreatment with heteropoly acids as substitutes for traditional H2SO4 in gamma
      valerolactone/water. By optimizing catalyst concentration, reaction time and
      temperature, the optimal lignin degradation conditions are obtained (130  degrees
      C, 3 h and 20 mM silicotungstic acid). SEM and FTIR measurements demonstrated the
      efficient lignin degradation ability of HPAs in the GVL/H2O solvent, with
      negligible damage to cellulose within the raw wood. Furthermore, an elaborated
      enzymatic hydrolysis study of the thus obtained cellulosic feedstock revealed its
      suitability for enzymatic digestion, with great potential as starting material
      for the production of fermentable sugar from biomass in future biorefinery
      applications.

PMID- 29653337
TI  - Investigation of microstructural abnormalities in white and gray matter around
      hippocampus with diffusion tensor imaging (DTI) in temporal lobe epilepsy (TLE).
AB  - OBJECTIVE: The objective of this study was to apply diffusion tensor imaging
      (DTI) to investigate microstructural abnormalities in temporal lobe epilepsy
      (TLE) with and without hippocampal sclerosis (HS). MATERIALS: Totally, 19
      patients with TLE with HS and 23 patients with TLE without HS were included.
      Fiber tracking fibers focused on the parahippocampal cingulum (PHC), cingulate
      gyrus (CG), and fornix (FORX). Fractional anisotropy (FA) and mean diffusivity
      (MD) values were obtained, and hippocampal volumes were measured. RESULTS:
      Compared with the contralateral side, for the HS group, FA values of ipsilateral
      CG and FORX were significantly decreased, and MD value of ipsilateral hippocampus
      was significantly higher, with significantly declined ipsilateral hippocampal
      volume. For the MRI-Neg group, FA values of ipsilateral CG, FORX, and hippocampus
      were significantly decreased, while MD values of ipsilateral FORX and hippocampus
      were significantly higher. Moreover, for the MRI-Neg group, the FA value of
      contralateral PHC was significantly decreased. Fractional anisotropy values of
      ipsilateral CG for both groups were significantly decreased, and FA value of
      ipsilateral FORX for the HS group was significantly decreased. Furthermore, MD
      value of ipsilateral hippocampus for the HS group was significantly higher, and
      FA value of ipsilateral hippocampus for the MRI-Neg group was significantly
      decreased. In addition, ipsilateral hippocampal volumes for both groups were
      significantly decreased. Fractional anisotropy value of ipsilateral CG and FORX
      had a correlation with the seizure frequency. CONCLUSION: Diffusion tensor
      imaging can detect microstructural abnormalities in brain from patients with TLE,
      which might be hard to find with routine Magnetic Resonance Imaging (MRI)
      sequence.

PMID- 29653338
TI  - Long-term effects of adjunctive perampanel on cognition in adolescents with
      partial seizures.
AB  - OBJECTIVE: The aim of this study was to evaluate long-term effects of adjunctive
      perampanel on cognition, efficacy, growth, safety, and tolerability in
      adolescents with inadequately controlled partial seizures. METHODS: Study 235, a
      multicenter, randomized, double-blind, placebo-controlled, parallel-group, Phase
      II study with an open-label extension phase (NCT01161524), was primarily designed
      to assess the effects of adjunctive perampanel on cognition. Patients (aged >=12
      to <18years) had a diagnosis of epilepsy with inadequately controlled partial
      seizures, with or without secondary generalization, despite receiving 1-3
      antiepileptic drugs. During the double-blind phase, adjunctive perampanel or
      placebo was administered over a 6-week titration period and a 13-week maintenance
      period up to 12mg/day. During the extension phase, all patients received
      perampanel. Data from the extension phase are presented here. Study endpoints
      included change from baseline in Cognitive Drug Research (CDR) measures of
      cognition, seizure frequency, growth, development, the occurrence of treatment
      emergent adverse events (TEAEs), and laboratory values. RESULTS: A total of 114
      patients entered the extension phase (prior double-blind treatment: placebo,
      n=41; perampanel, n=73). Perampanel had no effect on the CDR system global
      cognition score, continuity of attention, quality of episodic memory, quality of
      working memory, or speed of memory but was associated with a significant decline
      in power of attention at end of treatment compared with baseline (p=0.03). There
      were no effects on language skills or manual dexterity from baseline to end of
      treatment. At Weeks 40-52, median reduction in seizure frequency was 74.1%, and
      50% responder rate was 66.0%. There were no clinically relevant effects of
      perampanel on growth or development at end of treatment compared with baseline.
      Overall, 84.2% of patients experienced at least one TEAE and 70.2% experienced at
      least one treatment-related TEAE. The most common TEAEs were dizziness (29.8%)
      and somnolence (19.3%). The TEAEs resulted in the discontinuation of treatment in
      6.1% of patients. CONCLUSIONS: In keeping with the 19-week double-blind phase,
      long-term adjunctive treatment with perampanel did not have any significant
      overall effects on the CDR system global cognition score in adolescent patients
      with inadequately controlled partial seizures. Similar trends were observed
      across the individual CDR system domains. Adjunctive perampanel showed sustained
      long-term seizure control and had a safety and tolerability profile similar to
      that observed in prior clinical studies.

PMID- 29653339
TI  - Natural killer cells target and differentiate cancer stem-like
      cells/undifferentiated tumors: strategies to optimize their growth and expansion
      for effective cancer immunotherapy.
AB  - Natural killer (NK) cells are known to select and differentiate cancer stem-like
      cells/undifferentiated tumors via lysis, and secreted/membrane bound IFN-gamma
      and TNF-alpha respectively, resulting in the control of tumor growth. Several in
      vivo mouse models including humanized-BLT mice have been used to study the
      biology and significance of NK cells in selection/differentiation of stem-like
      tumors within the context of a reconstituted human immune system. In addition, we
      discuss the evidence and significance of NK cell loss at the pre-neoplastic
      stage. Therefore, because of their indispensable role in targeting
      CSCs/undifferentiated tumors, NK-cells should be placed high in the armamentarium
      of tumor therapy.

PMID- 29653340
TI  - Magnitude and variability of gait characteristics when walking on an irregular
      surface at different speeds.
AB  - Different modes of perturbations have been used to understand how individuals
      negotiate irregular surfaces, with a general notion that increased locomotion
      variability induces a positive training stimulus. Individuals tend to walk slower
      when initially exposed to such locomotion tasks, potentially influencing the
      magnitude and variability of biomechanical parameters. This study investigated
      theeffects of gait speed on lower extremity biomechanics when walking on an
      irregular (IS) and regular surface (RS). Twenty physically active males walked on
      a RS and IS at three different speeds (4 km/h, 5 km/h, 6 km/h). Lower extremity
      kinematics (300 Hz) and surface electromyography (3000 Hz) were recorded during
      the first 90 s of gait. Two-factor repeated measures ANOVA was used to determine
      surface and speed effects (p < 0.05). Gait speed influences walking biomechanics
      (kinematic and muscle activity parameters) the same irrespective of surface
      condition. As walking speed increased, sagittal shoe-surface angle, maximum ankle
      inversion, ankle abduction, knee and hip flexion increased during stance phase
      when walking on the IS and RS (p < 0.05). Increasing walking speed caused
      increased muscle activity of the tibialis anterior, peroneus longus,
      gastrocnemius medialis, vastus medialis and biceps femoris (p < 0.05) on the IS
      and RS during the gait cycle. Increased gait, kinematic and muscle activity
      variability was reported at lower walking speed on both the IS and RS. Further,
      irrespective of gait speed, walking on an IS triggers postural adjustments,
      higher muscle activity and increased gait variability compared to RS walking. Our
      findings suggest the benefits of training on the irregular surface may be further
      enhanced at slower gait speeds.

PMID- 29653341
TI  - Cotard syndrome in Tumefactive Multiple Sclerosis- A case report.

PMID- 29653342
TI  - School refusal in adolescents with systemic lupus erythematosus (SLE): A case
      series.

PMID- 29653343
TI  - Pulsus alternans induced by spinal anesthesia.

PMID- 29653344
TI  - A randomized controlled trial of comprehensive early intervention care in
      patients with first-episode psychosis in Japan: 1.5-year outcomes from the J-CAP
      study.
AB  - The first episode of psychosis represents a critical period wherein comprehensive
      early intervention in psychosis (EIP) may alter the course of illness. However,
      evidence from randomized controlled trials that have examined the impact of
      comprehensive EIP care on clinical and functional recovery assessed by
      independent blinded raters is limited. The objective of this study was to conduct
      a single-blinded multicenter trial comparing comprehensive EIP care and standard
      care in young patients with first-episode psychosis (FEP) in Japan (J-CAP Study).
      A total of 77 participants with FEP (aged 15-35 years) were randomized to receive
      standard care or specialized comprehensive EIP care and were followed up for 1.5
      years (trial no.: UMIN000005092). Function (measured with the Global Assessment
      of Functioning) and clinical remission (defined by internationally standardized
      criteria proposed by the Remission in Schizophrenia Working Group) were evaluated
      by independent raters who were blinded to group assignment. Dropout rate and
      other secondary outcomes were also examined. The specialized EIP care group had a
      higher clinical remission rate (odds ratio, 6.3; 95% confidence interval, 1.0
      37.9) and lower treatment dropout rate (odds ratio, 0.038; 95% confidence
      interval, 0.002-0.923) than the standard care group, even after adjusting for
      baseline characteristics. Functional improvement in the specialized EIP care
      group was slightly higher than that in the standard care group, but this
      difference was not statistically significant (p = 0.195). From the results, we
      conclude that comprehensive EIP care may provide advantages over standard care in
      patients with FEP.

PMID- 29653345
TI  - Isomerization of astilbin and its application for preparation of the four
      stereoisomers from Rhizoma Smilacis Glabrae.
AB  - Astilbin is the most predominant flavonoid in Rhizoma Smilacis Glabrae (RSG) with
      many bioactivities. The interconversion of the astilbin and its three
      stereoisomers was found with incubation of RSG extract at different temperatures,
      and the equilibrium ratios were calculated. Under certain conditions, neoastilbin
      would replace astilbin and become the predominant flavonoid in RSG extract. The
      effects of ascorbic acid, sucrose, sodium benzoate, beta-cyclodextrin (beta-CD)
      and common metal ions on the isomerization and decomposition of astilbin were
      studied. Ascorbic acid showed the best protective effect on the decomposition of
      astilbin and its isomers, which may be attributed to its reducing and radical
      scavenging ability. Besides, ascorbic acid also accelerated the isomerization of
      astilbin. beta-CD suppressed both isomerization and decomposition of astilbin
      through complexation between them. Most metal ions had inhibition effects on the
      isomerization of astilbin. Al3+ could almost completely inhibit the
      isomerization. The presence of Fe3+ caused the rapid decomposition of astilbin,
      and Cu2+ also showed weak effects. Based on the isomerization study, a novel and
      simple method for preparative separation of astilbin and neoastilbin from RSG
      sample was developed. Astilbin and neoastilbin with purity of 93% and yield of
      0.86% and 0.48% were obtained, respectively, which represent 46.8% of total
      flavonoids in RSG sample. By controlling the isomerization conditions, astilbin
      and neoastilbin could be used as the initial reactants to produce neoisoastilbin
      and isoastilbin, respectively.

PMID- 29653346
TI  - Simple and sensitive LC-MS/MS method for simultaneous determination of crizotinib
      and its major oxidative metabolite in human plasma: Application to a clinical
      pharmacokinetic study.
AB  - In this study, a fast, simple and sensitive liquid chromatography-mass
      spectrometry method was developed for simultaneous determination of crizotinib
      and its major oxidative metabolite crizotinib-lactam in human plasma. The plasma
      samples were deproteinated by using acetonitrile containing 0.1% formic acid as
      precipitant whereas the chromatographic separation was obtained on a C18 column
      with 0.1% formic acid aqueous and acetonitrile/methanol (v:v, 1:1) as mobile
      phase. The mass detector was operated in positive selected reaction monitoring
      mode. Precursor-to-product transitions were optimized to be m/z 450.1/260.1, m/z
      464.1/98.1, and m/z 326.1/291.1 for crizotinib, crizotinib-lactam and midazolam
      (internal standard), respectively. The established method was validated in
      accordance with guidance issued by Food and Drug Administration. The assay showed
      good linearity over the concentration ranges of 0.1-1000 ng/mL for crizotinib and
      0.1-400 ng/mL for crizotinib-lactam, with correlation coefficients more than
      0.999 (r > 0.999). The extraction recovery was more than 87.12%. No significant
      matrix effect and carryover were observed. The precision (RSD, %) was less than
      8.27%, whereas accuracy (RE, %) was within the range of -4.56 to 7.08%. The
      validated method has been successfully applied to the clinical pharmacokinetic
      study of crizotinib and crizotinib-lactam in human plasma after oral
      administration of crizotinib at a single dose of 250 mg. The results revealed
      that crizotinib was rapidly metabolized into its metabolite crizotinib-lactam and
      the in vivo exposure of crizotinib-lactam was 38.50% of that of crizotinib.

PMID- 29653347
TI  - Development and validation of a bioassay to evaluate binding of adalimumab to
      cell membrane-anchored TNFalpha using flow cytometry detection.
AB  - Physicochemical and structural properties of proteins used as active
      pharmaceutical ingredients of biopharmaceuticals are determinant to carry out
      their biological activity. In this regard, the assays intended to evaluate
      functionality of biopharmaceuticals provide confirmatory evidence that they
      contain the appropriate physicochemical properties and structural conformation.
      The validation of the methodologies used for the assessment of critical quality
      attributes of biopharmaceuticals is a key requirement for manufacturing under GMP
      environments. Herein we present the development and validation of a flow
      cytometry-based methodology for the evaluation of adalimumab's affinity towards
      membrane-bound TNFalpha (mTNFalpha) on recombinant CHO cells. This in vitro
      methodology measures the interaction between an in-solution antibody and its
      target molecule onto the cell surface through a fluorescent signal. The
      characteristics evaluated during the validation exercise showed that this
      methodology is suitable for its intended purpose. The assay demonstrated to be
      accurate (r2 = 0.92, slope = 1.20), precise (%CV <= 18.31) and specific (curve
      fitting, r2 = 0.986-0.997) to evaluate binding of adalimumab to mTNFalpha. The
      results obtained here provide evidence that detection by flow cytometry is a
      viable alternative for bioassays used in the pharmaceutical industry. In
      addition, this methodology could be standardized for the evaluation of other
      biomolecules acting through the same mechanism of action.

PMID- 29653348
TI  - Increased oxidative stress in the mitochondria isolated from lymphocytes of
      bipolar disorder patients during depressive episodes.
AB  - The present study aims to investigate the oxidative stress parameters in isolated
      mitochondria, as well as looking at mitochondrial complex activity in patients
      with Bipolar Disorder (BD) during depressive or euthymic episodes. This study
      evaluated the levels of mitochondrial complex (I, II, II-III and IV) activity in
      lymphocytes from BD patients. We evaluated the following oxidative stress
      parameters: superoxide, thiobarbituric acid reactive species (TBARS) and carbonyl
      levels in submitochondrial particles of lymphocytes from bipolar patients. 51
      bipolar patients were recruited into this study: 34 in the euthymic phase, and 17
      in the depressive phase. Our results indicated that the depressive phase could
      increase the levels of mitochondrial superoxide, carbonyl and TBARS, and
      superoxide dismutase, and could decrease the levels of mitochondrial complex II
      activity in the lymphocytes of bipolar patients. It was also observed that there
      was a negative correlation between the Hamilton Depression Rating Scale (HDRS)
      and complex II activity in the lymphocytes of depressive bipolar patients. In
      addition, there was a positive correlation between HDRS and superoxide,
      superoxide dismutase, TBARS and carbonyl. Additionally, there was a negative
      correlation between complex II activity and oxidative stress parameters. In
      conclusion, our results suggest that mitochondrial oxidative stress and
      mitochondrial complex II dysfunction play important roles in the depressive phase
      of BD.

PMID- 29653349
TI  - The role of lifetime anxiety history in the course of bipolar spectrum disorders.
AB  - Individuals with bipolar spectrum disorder (BSD) frequently meet criteria for
      comorbid anxiety disorders, and anxiety may be an important factor in the
      etiology and course of BSDs. The current study examined the association of
      lifetime anxiety disorders with prospective manic/hypomanic versus major
      depressive episodes. Participants were 244 young adults (aged 17-26) with milder
      forms of BSDs (i.e., bipolar-II, cyclothymia, BD-NOS). First, bivariate analyses
      assessed differences in baseline clinical characteristics between participants
      with and without DSM-IV anxiety diagnoses. Second, negative binomial regression
      analyses tested whether lifetime anxiety predicted number of manic/hypomanic or
      major depressive episodes developed during the study. Third, survival analyses
      evaluated whether lifetime anxiety predicted time to onset of manic/hypomanic and
      major depressive episodes. Results indicated that anxiety history was associated
      with greater illness severity at baseline. Over follow-up, anxiety history
      predicted fewer manic/hypomanic episodes, but did not predict number of major
      depressive episodes. Anxiety history also was associated with longer time to
      onset of manic/hypomanic episodes, but shorter time to onset of depressive
      episodes. Findings corroborate past studies implicating anxiety disorders as
      salient influences on the course of BSDs. Moreover, results extend prior research
      by indicating that anxiety disorders may be linked with reduced manic/hypomanic
      phases of illness.

PMID- 29653350
TI  - Relevance of treated cocaine users' retrospective memory of first cocaine use.
AB  - Little is known regarding between-subject variability in the subjective effects
      of first cocaine use. This study retrospectively assesses the subjective effects
      of first cocaine use in 160 current treatment-seeking cocaine use disorder
      patients. Subjective effects of first cocaine use were evaluated with an ad-hoc
      questionnaire used for cannabis effects. A principal component analysis (PCA) was
      performed, with resulting factors correlated with clinical variables (alpha =
      0.05). Four factors emerged in the PCA, namely Anxiety (accounting for 21.5% of
      questionnaire variance), Disinhibition (17.3%), Tachypsychia (16%) and Calmness
      (13%). Male gender was associated with Disinhibition and Tachypsychia. Cocaine
      severity factors were associated with Disinhibition, Tachypsychia and Calmness.
      Opiate, sedative and poppers uses were associated with Anxiety, Tachypsychia and
      Calmness. The retrospective assessment of the subjective effects of first cocaine
      use shows significant variability. The different dimensions of subjective first
      effects are influenced by age, gender and previous substance use history, as well
      as characteristics of first cocaine use and cocaine-related outcomes.

PMID- 29653351
TI  - Early non-invasive detection of breast cancer using exhaled breath and urine
      analysis.
AB  - The main focus of this pilot study is to develop a statistical approach that is
      suitable to model data obtained by different detection methods. The methods used
      in this study examine the possibility to detect early breast cancer (BC) by
      exhaled breath and urine samples analysis. Exhaled breath samples were collected
      from 48 breast cancer patients and 45 healthy women that served as a control
      group. Urine samples were collected from 37 patients who were diagnosed with
      breast cancer based on physical or mammography tests prior to any surgery, and
      from 36 healthy women. Two commercial electronic noses (ENs) were used for the
      exhaled breath analysis. Urine samples were analyzed using Gas-Chromatography
      Mass-Spectrometry (GC-MS). Statistical analysis of results is based on an
      artificial neural network (ANN) obtained following feature extraction and feature
      selection processes. The model obtained allows classification of breast cancer
      patients with an accuracy of 95.2% +/- 7.7% using data of one EN, and an accuracy
      of 85% for the other EN and for urine samples. The developed statistical analysis
      method enables accurate classification of patients as healthy or with BC based on
      simple non-invasive exhaled breath and a urine sample analysis. This study
      demonstrates that available commercial ENs can be used, provided that the data
      analysis is carried out using an appropriate scheme.

PMID- 29653352
TI  - Online molecular image repository and analysis system: A multicenter
      collaborative open-source infrastructure for molecular imaging research and
      application.
AB  - Molecular imaging serves as an important tool for researchers and clinicians to
      visualize and investigate complex biochemical phenomena using specialized
      instruments; these instruments are either used individually or in combination
      with targeted imaging agents to obtain images related to specific diseases with
      high sensitivity, specificity, and signal-to-noise ratios. However, molecular
      imaging, which is a multidisciplinary research field, faces several challenges,
      including the integration of imaging informatics with bioinformatics and medical
      informatics, requirement of reliable and robust image analysis algorithms,
      effective quality control of imaging facilities, and those related to
      individualized disease mapping, data sharing, software architecture, and
      knowledge management. As a cost-effective and open-source approach to address
      these challenges related to molecular imaging, we develop a flexible,
      transparent, and secure infrastructure, named MIRA, which stands for Molecular
      Imaging Repository and Analysis, primarily using the Python programming language,
      and a MySQL relational database system deployed on a Linux server. MIRA is
      designed with a centralized image archiving infrastructure and information
      database so that a multicenter collaborative informatics platform can be built.
      The capability of dealing with metadata, image file format normalization, and
      storing and viewing different types of documents and multimedia files make MIRA
      considerably flexible. With features like logging, auditing, commenting, sharing,
      and searching, MIRA is useful as an Electronic Laboratory Notebook for effective
      knowledge management. In addition, the centralized approach for MIRA facilitates
      on-the-fly access to all its features remotely through any web browser.
      Furthermore, the open-source approach provides the opportunity for sustainable
      continued development. MIRA offers an infrastructure that can be used as cross
      boundary collaborative MI research platform for the rapid achievement in cancer
      diagnosis and therapeutics.

PMID- 29653353
TI  - A statistical shape model of the left ventricle from real-time 3D
      echocardiography and its application to myocardial segmentation of cardiac
      magnetic resonance images.
AB  - OBJECT: We present in this paper the application of a statistical shape model of
      the left ventricle (LV) built from transthoracic real time 3D echocardiography
      (3DE) to segment the LV endocardium and epicardium in cardiac magnetic resonance
      (CMR) images. MATERIAL AND METHODS: The LV model was built from a training
      database constituted by over 9000 surfaces obtained from retrospectively selected
      3DE examination of 435 patients with various pathologies. Three-dimensional
      segmentation of the endocardium and the epicardium was obtained by processing CMR
      images acquired in 30 patients with a dedicated active shape modelling (ASM)
      algorithm using the proposed LV model. RESULTS: The segmentation results obtained
      with the proposed method were compared with those obtained by the manual
      reference technique; similarity was proven by computing: i) point to surface
      distance (<2 mm), ii) Dice similarity coefficient (>89%), iii) Hausdorff distance
      (~5 mm). This was furthermore confirmed by equivalence testing, linear regression
      and Bland Altman analysis applied on derived clinical parameters, such as LV
      volumes and mass. CONCLUSIONS: This study showed the potential usefulness of the
      proposed inter-modal ASM approach featuring a 3DE-based LV model for the 3D
      segmentation of the LV myocardium in CMR images.

PMID- 29653354
TI  - A self-tuned graph-based framework for localization and grading prostate cancer
      lesions: An initial evaluation based on multiparametric magnetic resonance
      imaging.
AB  - Multiparametric magnetic resonance imaging (mpMRI) has been established as the
      state-of-the-art examination for the detection and localization of prostate
      cancer lesions. Prostate Imaging-Reporting and Data System (PI-RADS) has been
      established as a scheme to standardize the reporting of mpMRI findings. Although
      lesion delineation and PI-RADS ratings could be performed manually, human
      delineation and ratings are subjective and time-consuming. In this article, we
      developed and validated a self-tuned graph-based model for PI-RADS rating
      prediction. 34 features were obtained at the pixel level from T2-weighted (T2W),
      apparent diffusion coefficient (ADC) and dynamic contrast enhanced (DCE) images,
      from which PI-RADS scores were predicted. Two major innovations were involved in
      this self-tuned graph-based model. First, graph-based approaches are sensitive to
      the choice of the edge weight. The proposed model tuned the edge weights
      automatically based on the structure of the data, thereby obviating empirical
      edge weight selection. Second, the feature weights were tuned automatically to
      give heavier weights to features important for PI-RADS rating estimation. The
      proposed framework was evaluated for its lesion localization performance in mpMRI
      datasets of 12 patients. In the evaluation, the PI-RADS score distribution map
      generated by the algorithm and from the observers' ratings were binarized by
      thresholds of 3 and 4. The sensitivity, specificity and accuracy obtained in
      these two threshold settings ranged from 65 to 77%, 86 to 93% and 85 to 88%
      respectively, which are comparable to results obtained in previous studies in
      which non-clinical T2 maps were available. The proposed algorithm took 10s to
      estimate the PI-RADS score distribution in an axial image. The efficiency
      achievable suggests that this technique can be developed into a prostate MR
      analysis system suitable for clinical use after a thorough validation involving
      more patients.

PMID- 29653355
TI  - Monte Carlo method for gamma spectrometry based on GEANT4 toolkit: Efficiency
      calibration of BE6530 detector.
AB  - The combination of gamma-ray spectrometry, the development of related Monte Carlo
      method and the GEANT4 (GEometry ANd Tracking) toolkit have been developed for
      gamma spectrometry simulation. The main objective was to validate simulation
      models of broad energy germanium (BEGe) detector geometry built in our laboratory
      (BE6530 model). Monte Carlo simulation of the geometry of BE6530 detector for
      efficiency calibration was carried out with GEANT4 toolkit. The simulated
      efficiencies curves using MC were compared with experimental results. Measurement
      uncertainties for both simulation and experimental estimations of the efficiency
      were assessed in order to see whether the consequences of the realistic
      measurement fall inside adequate cut-off points. The validation of the simulation
      was carried out by experimentally estimating the activity concentration in a
      reference sample and the comparison showed good correlation between experimental
      and simulation. Therefore, from the outcomes of this study, it can be concluded
      that Monte-Carlo simulation is a helpful, reasonable option that additionally
      gives more prominent adaptability, greater flexibility, precision and accuracy,
      and gained time when determining the detector response and efficiency in routine
      of environmental radioactivity monitoring.

PMID- 29653356
TI  - Interaction of toxic chemicals with microplastics: A critical review.
AB  - Occurrence of microplastics (MPs) in the environment has attracted great
      attention as it has become a global concern. This review aims to systematically
      demonstrate the role of marine microplastic as a novel medium for environmental
      partitioning of chemicals in the ocean, which can cause toxic effects in the
      ecological environment. This review assimilated and analyzed available data
      published between 1972 and 2017 on the interaction between MPs and selected
      chemicals. Firstly, the review analyzes the occurrence of chemicals in MPs and
      outlines their distribution patterns. Then possible mechanisms of the interaction
      between MPs and organic chemicals and potential controlling factors were
      critically studied. Finally, the hazards of MPs and affiliated organic chemicals
      to marine organisms were shortly summarized.

PMID- 29653357
TI  - Controlling bromate formation in the Co(II)/peroxymonosulfate process by ammonia,
      chlorine-ammonia and ammonia-chlorine pretreatment strategies.
AB  - The Co(II)/peroxymonosulfate (Co(II)/PMS) process, producing sulfate radicals
      (SO4*-), effectively removes organic pollutants in water, while producing a
      significant amount of bromate (BrO3-) in the presence of bromide (Br-). This
      paper investigates the ammonia (NH3) addition, chlorine-ammonia (Cl2-NH3) and
      ammonia-chlorine (NH3-Cl2) pretreatment strategies in controlling BrO3- formation
      in 20 min in the Co(II)/PMS process at pH 4.0. The addition of NH3 retarded the
      BrO3- formation, but only at a reduction level of about 9.5% for NH3
      concentration of 50 MUM, and was mainly attributed to the protonation of NH3 at
      pH 4 (99.99% as NH4+, did not react with HOBr). Both the Cl2-NH3 and NH3-Cl2
      pretreatment strategies at HOCl and NH3 dosages of 15 and 50 MUM, respectively,
      reduced 95% or more of the overall BrO3- formation and retarded the BrO3-
      formation, with the NH3-Cl2 pretreatment strategy outperforming Cl2-NH3. The
      reduction of the BrO3- formation was mainly attributed to the formation of
      monochloramine (NH2Cl) in both pretreatment strategies. NH2Cl effectively
      outcompetes SO4*- to react with HOBr and forms NHBrCl, with the apparent reaction
      rate constant between NH2Cl and HOBr more than 100 times faster than that between
      SO4*- and HOBr. However, the oxidation/degradation of NHBrCl in the Co(II)/PMS
      process reforms HOBr, and, although less in quantity, is oxidized to BrO3- at
      higher Co(II) and Br- concentrations. Thus, the NH3-Cl2 and Cl2-NH3 pretreatment
      strategies inhibit the BrO3- formation more significantly at lower Co(II) and Br-
      concentrations. In all cases, the generation of SO4*- in 20 min was not affected
      by the implementation of the three BrO3- pretreatment strategies.

PMID- 29653358
TI  - Anaerobic treatment of N, N-dimethylformamide-containing wastewater by co
      culturing two sources of inoculum.
AB  - The complete methanogenic degradation of N, N-dimethylformamide (DMF) was
      achieved in this study. Initially, DMF was found to be feebly degradable by a lab
      scale submerged anaerobic membrane bioreactor (SAnMBR) using normal anaerobic
      digestion sludge (ADS) even after 120-day's culturing. However, aerobic DMF
      degrading activated sludge (AS) was rapidly cultivated in a continuous aeration
      reactor (CAR). A specially designed anaerobic co-cultured sludge (ACS) made by
      artificially mixing AS with ADS was successfully domesticated by a long term
      repeated batch experiment. The results demonstrated that ACS could effectively
      degrade over 5000 mg L-1 DMF for methane recovery. The metabolic pathway and
      stoichiometric equation of DMF methanogenic degradation were also revealed and
      verified in detail. It was confirmed that under the anaerobic condition, with the
      help of enzyme, DMF converts into dimethylamine and formic acid, and the
      intermediates are effectively fermented through methylotrophic/hydrogenotrophic
      methanogenesis. Analysis of the microbial community suggested that some
      facultatively anaerobic bacteria played the key roles in methanogenic degradation
      due to their DMF-hydrolyzing ability. By co-culturing two sources of inoculum
      under the anaerobic condition, the symbiosis of facultatively anaerobic DMF
      hydrolyzing bacteria and methylotrophic/hydrogenotrophic methanogens makes
      methanogenic degradation of DMF available. This study also provides a novel
      sludge cultivation method for anaerobic treatment of degradation-resistant
      organics.

PMID- 29653359
TI  - The role of the gut microbiota in the pathology and prevention of liver disease.
AB  - Several microorganisms belonging to the intestinal microbiota act in an ecosystem
      responsible for maintaining the homeostasis and vital functions of human beings.
      From birth to old age the diversity of the intestinal microbiota may change due
      to environmental factors such as nutrition, immunity, diseases or the use of
      antibiotics leading to dysbiosis. Improvement in microbiota diversity can be
      achieved by modifying related risk factors through changes in lifestyle and a
      healthy diet. Besides, the addition of probiotics, prebiotics or the combination
      of both (symbiotics), can result in the improvement of the intestinal
      permeability, inflammatory pathways and the immune system. Also, the use of
      probiotics prevents harmful bacteria and their derived products (e.g.,
      bacteriocins, endotoxins, hydrogen sulfide, etc.) to leak through the intestinal
      wall to the circulation that results in the activation of signaling pathways that
      may be implicated in liver disease. The liver receives a constant flow of noxious
      entities that promote inflammation and oxidative stress. The use of probiotics
      with clinical evidence in liver disease, represent a novel therapeutic
      alternative, inducing positive changes in the balance of the intestinal
      microbiota which lead to improvement in liver function tests (AST and ALT),
      decreasing tumor necrosis factor-alpha (TNF-alpha), andblood cholesterol, among
      other risk factors. In this review, we discuss the main elements that play a
      leading role in the development of steatosis as well as the benefits of using
      probiotics and the impact in the quality of life of patients that develop
      cirrhosis.

PMID- 29653360
TI  - Involvement of the NO/sGC/cGMP/K+ channels pathway in vascular relaxation evoked
      by two non-quinazoline alpha1-adrenoceptor antagonists.
AB  - The aim of this study was to explore the alpha1-adrenoceptor-independent
      mechanisms involved in the vasorelaxant properties of two non-quinazoline alpha1
      adrenoceptors antagonists (MH-76 and MH-79). Endothelium intact and endothelium
      denuded rat aorta was contracted with 1 MUM phenylephrine to plateau, and the
      vasodilatory effect of MH-76 and MH-79 was examined in the absence or presence of
      inhibitors of the different signal transduction pathways. cGMP concetration was
      measured in rat aorta (enzyme immunoassay kit). In human aortic endothelial cells
      (HAEC) NO production was examined using a DAF-FM DA fluorescent indicator,
      whereas in human aortic smooth muscle cells the influence of the title compounds
      on K+ efflux was evaluated. The vasorelaxant effect of MH-76 and MH-79 was
      attenuated by endothelium removal, Nomega-Nitro-l-arginine methyl ester (L-NAME)
      and 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) pretreatment to the level
      characteristic for alpha1-adrenoreceptor blocking activity. In addition, the MH
      76 and MH-79 induced relaxation was reduced by K+ channels blockers. In
      endothelium intact rat aorta, MH-76 and MH-79 caused an increase in cGMP level,
      whereas in HAEC they increased NO generation. In contrast, the reference,
      quinazoline based alpha1-antagonist prazosin, did not influence NO production.
      Our findings suggest that the mechanisms underlying the vasodilatory properties
      of non-quinazoline based alpha1-adrenoceptors antagonists MH-76 and MH-79 involve
      not only alpha1-adrenoceptor blocking activity but also the activation of the
      endothelial NO-cGMP signalling pathway and the subsequent opening of K+ channels.
      Our studies show that such double mechanism of action is superior to pure alpha1
      adrenoceptor blockade, and may be considered as a promising alternative for the
      prevention and treatment of cardiovascular diseases.

PMID- 29653361
TI  - LncRNA ASAP1-IT1 positively modulates the development of cholangiocarcinoma via
      hedgehog signaling pathway.
AB  - Over the past decades, lncRNAs have attracted more and more attentions of
      researchers. It has been verified that lncRNAs can modulate multiple biological
      behaviors in various human cancers. LncRNA ASAP1-IT1 has been certified to be a
      tumor facilitator in several malignant tumors. This study aims to investigate the
      effects of dysregulated ASAP1-IT1 on biological processes of Cholangiocarcinoma.
      The high expression level of ASAP1-IT1 was tested in Cholangiocarcinoma tissues
      and cells with qRT-PCR. Upregulation of ASAP1-IT predicted the unfavorable
      prognosis for Cholangiocarcinoma patients. Next, ASAP1-IT1 was knocked down in
      cancerous cells for loss-of function assay. MTT, colony formation and transwell
      and western bot assays were performed to demonstrate the specific impacts of
      ASAP1-IT1 on proliferation, migration and EMT progression of Cholangiocarcinoma.
      Cells. As a results, the Cholangiocarcinoma progression was inhibited. Hedgehog
      signaling pathway has been discovered to be a treatment target in
      Cholangiocarcinoma. In this study, the interaction between ASAP1-IT1 and hedgehog
      pathway was specifically investigated. Smo and Gli1, two hedgehog-related
      proteins were examined in Cholangiocarcinoma cells. The results of qRT-PCR and
      western blot assay suggested that ASAP1-IT1 could positively modulate Smo and
      Gli1 in Cholangiocarcinoma. Finally, rescue assays were carried out to prove that
      ASAP1-IT1 could improve Cholangiocarcinoma progression and development via
      hedgehog signaling pathway.

PMID- 29653362
TI  - The long noncoding RNA ZFAS1 facilitates bladder cancer tumorigenesis by sponging
      miR-329.
AB  - The incidence and mortality rate of bladder cancer have dramatically expanded, so
      it's urgent to discover new biomarker and therapeutic target for bladder cancer.
      Recently, lncRNA has been identified as oncogene or tumor suppressor to regulate
      the tumorigenesis. LncRNA ZFAS1 has been confirmed as oncogene in various tumors.
      However, the expression, function, and underlying mechanism of ZFAS1 in bladder
      carcinogenesis have yet to be totally clarified. In the current study, our data
      demonstrated that ZFAS1 expression was significantly upregulated in bladder
      cancer tissues and cell lines. Furthermore, Kaplan-Meier analysis revealed that
      high ZFAS1 expression was significantly associated with unfavorable progression
      free survival (PFS) (P = 0.0034 < 0.01) and overall survival (OS) (P = 0.0041 <
      0.01) of bladder cancer patients. Moreover, silencing of ZFAS1 expression could
      markedly suppress bladder cancer cells proliferation and colony formation, arrest
      cell cycle, promote cell apoptosis and inhibit cell migration in vitro. In
      addition, bioinformatics analysis, luciferase reporter assay, and pull down assay
      revealed that ZFAS1 straightly interacted with miR-329. Lastly, rescue
      experiments confirmed that miR-329 inhibitor reversed the tumor suppressing roles
      of ZFAS1 knockdown on bladder cancer cells. Collectively, our results illuminated
      that ZFAS1 could serve as an oncogene in the tumorigenesis of bladder cancer, and
      discovered the functional regulatory network of ZFAS1 sponging miR-329.

PMID- 29653363
TI  - Trapidil improves hemodynamic, echocardiographic and redox state parameters of
      right ventricle in monocrotaline-induced pulmonary arterial hypertension model.
AB  - BACKGROUND: Pulmonary arterial hypertension is a disease characterized by
      increased pulmonary vascular resistance and redox imbalance, leading to failure
      of right ventricle. Trapidil has been described to improve the redox balance and
      cardiac conditions. HYPOTHESIS: Trapidil can improve the redox balance and
      contribute to functional improvements of the RV in PAH. METHODS AND RESULTS:
      Male, 5week-old Wistar rats were divided into four groups: Control, Control +
      Trapidil, Monocrotaline and Monocrotaline + Trapidil. PAH was induced by an
      intraperitoneal injection of monocrotaline 60 mg/kg at day 0. Treatment started
      at day 7 (5 or 8 mg/kg/day) until day 14, when animals were euthanized after
      echocardiography and catheterism. Right ventricular systolic pressure and
      pressure/time derivatives were increased in monocrotaline animals. The increased
      right ventricular diameters in monocrotaline groups were reduced with trapidil.
      Monocrotaline groups showed higher lipid peroxidation and glutathione peroxidase
      activity. Trapidil reduced NADPH oxidases activities and increased the reduced
      glutathiones/total glutathiones ratio. Protein expression of phospholamban in RV
      was diminished in monocrotaline groups, whereas expression of RyR and SERCA was
      enhanced in the groups treated with trapidil. CONCLUSION: Our data suggest that
      trapidil induces an improvement in RV remodeling in PAH model, mitigating the
      progression of the disease.

PMID- 29653364
TI  - MicroRNA-20a protects human aortic endothelial cells from Ox-LDL-induced
      inflammation through targeting TLR4 and TXNIP signaling.
AB  - MiR-20a has been previously reported to participate in the development of various
      human diseases. However, the role of miR-20a in the pathology of atherosclerosis
      remains elusive. The present study aimed to reveal the relationship between miR
      20a expression and atherosclerosis using in vitro cell model. The expression
      level of miR-20a was detected in human aortic endothelial cells (HAECs) under Ox
      LDL exposure. Meanwhile, the regulatory effects of miR-20a on predicted targets
      (TLR4 and TXNIP) were also determined. Moreover, the levels of key proteins and
      inflammatory mediators in TLR4 and NLRP3 signaling were detected to further
      confirm the regulatory effects of miR-20a. We found that miR-20a expression was
      repressed under Ox-LDL condition, and both TLR4 and TXNIP acted as regulatory
      targets of miR-20a. Overexpressed miR-20a reduced ROS generation under Ox-LDL
      treatment, and this effect was restored by forced expression of TLR4. Moreover,
      key molecules (including MyD88, TRIF, phosphorylated NF-kappaB (p65), NLRP3, ASC,
      cleaved caspase-1, ICAM-1 and IL-1beta) in TLR4 and NLRP3 signaling were
      significantly repressed under miR-20a overexpression. In conclusion, miR-20a
      could negatively regulate TLR4 and NLRP3 signaling to protect HAECs from
      inflammatory injuries, which provides a new insight into the inhibition of
      atherosclerotic development.

PMID- 29653365
TI  - Beneficial health effects of lupenone triterpene: A review.
AB  - There are a large number of new structure compounds with good pharmacological
      activity in the natural plants, can be applied to the treatment of human
      diseases. Finding active ingredients from the plants is one of the important ways
      to develop new drugs. Triterpenes are widespread in plants, and lupenone belongs
      to lupane type triterpenoids. Lupenone is very common natural ingredient
      distributed in multi-family plants including Asteraceae, Balanophoraceae,
      Cactaceae, Iridaceae, Musaceae, Urticaceae, Leguminosae, Bombacaceae, etc., but
      its distribution has no regular. The consumption of lupenone in vegetarian diet
      is high in human life. Pharmacological screening of lupenone revealed various
      pharmacological activities including anti-inflammatory, anti-virus, anti
      diabetes, anti-cancer, improving Chagas disease without major toxicity. Based on
      these important pharmacological activities, this review provides detailed account
      of pre-clinical studies conducted to determine the utility of lupenone as a
      therapeutic and chemopreventive agent for the treatment of various diseases.

PMID- 29653366
TI  - Bufalin inhibits glioblastoma growth by promoting proteasomal degradation of the
      Na+/K+-ATPase alpha1 subunit.
AB  - Chansu is a traditional Chinese medicine that is generally recognized as a
      specific inhibitor of Na+/K+-ATPase. Bufalin, an active component of Chansu, is
      an endogenous steroid hormone with great potential as a cancer treatment.
      However, the mechanism by which it exerts its antitumor activity requires further
      research. Currently, the alpha1 subunit of Na+/K+-ATPase (ATP1A1) is known to
      exert important roles in tumorigenesis, and the precise mechanisms underlying the
      effect of Bufalin on the Na+/K+-ATPase alpha1 subunit was therefore investigated
      in this study to determine its role in glioblastoma treatments. The effect of
      ATP1A1 on the sensitivity of glioblastoma cells to Bufalin was investigated using
      MTT assays, RT-PCR and siRNA. Western blot was also used to explore the important
      roles of the ubiquitin-proteasome pathway in the Bufalin-mediated inhibition of
      ATP1A1. Xenografted mice were used to examine the anti-tumor activity of Bufalin
      in vivo. LC-MS/MS analysis was performed to determine the ability of Bufalin to
      traverse the blood-brain barrier (BBB). The results indicated that Bufalin
      inhibited the expression of ATP1A1 in glioblastoma by promoting the activation of
      proteasomes and the subsequent protein degradation of ATP1A1, while Bufalin had
      no effect on ATP1A1 protein synthesis. Bufalin also inhibited the expression of
      ATP1A1 in xenografted mice and significantly suppressed tumor growth. These data
      should contribute to future basic and clinical investigations of Bufalin. In
      conclusion, Bufalin significantly inhibited the expression of ATP1A1 in
      glioblastoma cells by activating the ubiquitin-proteasome signaling pathway.
      Bufalin may therefore have the potential to be an effective anti-glioma drug for
      human glioblastoma in the future.

PMID- 29653367
TI  - Upregulation of lncRNA PlncRNA-1 indicates the poor prognosis and promotes glioma
      progression by activation of Notch signal pathway.
AB  - Prostate cancer-up-regulated long noncoding RNA 1(PlncRNA-1) has been
      demonstrated to be increased in several cancers, which plays an oncogenic role in
      the development of cancer. However, the exact functions and molecular mechanism
      of PlncRNA-1 in the tumorigenesis of glioma has not been studied. In present
      work, we firstly identified that PlncRNA-1 expression levels were prominently
      augmented in glioma patient tissues and glioma cell lines compared with adjacent
      noncancerous tissue and normal cells, respectively. Moreover, Kaplan-Meier
      survival analysis indicated that glioma patients with high PlncRNA-1 expression
      had shorter overall survival (OS) and progression-free survival (PFS) than those
      with low PlncRNA-1 expression. Furthermore, loss-of-function assay showed that
      PlncRNA-1 knockdown dramatically reduced cell proliferation, colony formation,
      and promoted apoptosis of glioma cell lines. In addition, overexpression of
      PlncRNA-1 promoted cell proliferation, stimulated cell colony formation, and
      inhibited cell apoptosis in NHA cells. Mechanically, our results showed that
      PlncRNA-1 significantly promoted activation of the Notch signal pathway through
      regulation of Notch-1, Jag-1, and Hes-1 expression. Collectively, our results
      implied that lncRNA PlncRNA-1 may exert tumor-promoting role in the development
      and progression of glioma through modulation of Notch signal pathway, providing a
      candidate therapeutic target for patients with glioma.

PMID- 29653368
TI  - Synthesis of F127/PAA hydrogels for removal of heavy metal ions from organic
      wastewater.
AB  - Organic matters in wastewater dramatically impaired the removal capability of
      adsorbents to heavy metal ions, thus greatly limited their applications for real
      systems. Here we fabricated the F127/PAA hydrogels that could effectively remove
      Cu2+ and Hg2+ from organic wastewater due to their anti-fouling properties
      against organic matters. The F127/PAA hydrogels performed high swelling ratio and
      mechanical stress, showing maximum adsorption capacities of Cu2+ and Hg2+ at
      283.4 and 222.1 mg/g, respectively. For the BSA containing water, the removal
      ratio of Cu2+ and Hg2+ by F127/PAA hydrogels could reach to 94.0% and 70.2%,
      respectively. For the humic acid containing water, the corresponding data were
      89.5% and 72.1%. Besides, five cyclic adsorption-desorptions in humic acid
      solution and simulated cosmetic wastewater only slightly decreased the removal
      efficiencies of F127/PAA hydrogels to Cu2+ and Hg2+. Our results suggested the
      potential application of the F127/PAA hydrogels in treatment of real organic
      wastewater.

PMID- 29653369
TI  - Biocompatible Fe3+-TA coordination complex with high photothermal conversion
      efficiency for ablation of cancer cells.
AB  - Near-infrared (NIR) light absorbing nanomaterials, which can convert light to
      heat energy, have great prospects in biomedical applications. In the current
      work, Fe3+-TA (Tannic Acid) coordination complex formed by simple mixing of
      tannic acid and FeCl3 solutions was explored as a novel photothermal agent. Due
      to the strong absorbance in the near-infrared region induced by the coordination
      effect between TA molecule and Fe3+ ion, the as-prepared Fe3+-TA complex
      exhibited excellent photothermal performance with high photothermal conversion
      efficiency of 77.3% and high photothermal stability. Upon the exposure to Fe3+-TA
      aqueous dispersions with a concentration of 0.125 mg/mL, the cell mortality of
      HeLa cells was more than 85% after being irradiated for 10 min under NIR light
      (808 nm, 6 W cm-2). Besides, the Fe3+-TA complex exhibited ultralow cytotoxicity
      since only biocompatible tannic acid and iron ions were used as raw materials.
      Therefore, the merits of simple and convenient fabrication method, high
      photothermal conversion efficiency and excellent biocompatibility endow the high
      potential of Fe3+-TA complex as a photothermal agent for biomedical applications.

PMID- 29653370
TI  - Fabrication of blue-fluorescent nanodiamonds modified with alkyl isocyanate for
      cellular bioimaging.
AB  - This paper describes the fabrication of water-dispersible nanodiamond (ND)
      clusters with blue fluorescence for cellular bioimaging. Poly(ethylene glycol)
      carboxyl methyl acid (mPEG-COOH) and alkyl isocyanates with different chain
      lengths were conjugated onto the surface of the ND clusters for water
      dispersibility and fluorescence via carbodiimide chemistry. The relative
      fluorescence intensity was increased with the increases in the chain length of
      alkyl isocyanate and also their conjugated concentration. The ND clusters
      (average size of 37.6 nm and zeta potential of 26.6 mV) with mPEG-COOH and
      octadecyl isocyanate (ODI) emitted relatively higher blue fluorescence intensity
      under excitation at 350 nm as well as favorable water dispersibility. After
      cellular uptake of the ND clusters, blue fluorescence inside the cells was
      confirmed by confocal laser scanning microscopy. The ND clusters conjugated with
      mPEG-COOH and ODI can potentially be used for cellular bioimaging.

PMID- 29653371
TI  - Foreword: Special issue in honor of Alexander J. (Lex) Vega.

PMID- 29653372
TI  - Letter to the Editor: History and clinical implications of PAPP-A2 in human
      growth: When reflecting on idiopathic short stature leads to a specific and new
      diagnosis: Understanding the concept of "low IGF-I availability".
AB  - As a result of our publication of the first patients with short stature due to a
      mutation in the gene for PAPP-A2 the question, "Why did you continue to study
      these patients when they were not more than 2 SDS below normal?" has been
      proposed surprisingly frequently. We would like to communicate our opinions on
      why these patients were studied and share the experience on how this process took
      place. In addition, the choice of treatment is also discussed. We believe that
      this discovery process is a good example of good clinical practice and
      international collaboration.

PMID- 29653373
TI  - Combined effect of salt and drought on boron toxicity in Puccinellia tenuiflora.
AB  - Boron toxicity is a worldwide problem, usually accompanied by salt (NaCl) and
      drought. The combined stresses may induce complex toxicity to the plant. The aim
      of the present study was to investigate how the combined stresses of salt and
      drought affect B toxicity in plants. Puccinellia tenuiflora seedlings were
      planted in vermiculite. A three (B) * three (salt) * three (drought) factorial
      experiment (for a total of 27 treatments) was conducted. After a 30-day
      cultivation, plants were harvested to determine dry weight and the concentrations
      of B, Na+, K+, Ca2+, and Mg2+. Plant growth was inhibited by B toxicity, which
      was alleviated by salt and drought. B stress enhanced B uptake and transport of
      the plant, which was inhibited by salt and drought. B stress had a little effect
      on K+ and Na+ concentration and caused Ca2+ and Mg2+ accumulation in the plant.
      Salt addition increased Na+ concentration and inhibited Ca2+ and Mg2+
      accumulation. Drought addition inhibited Na+ accumulation and enhanced Ca2+ and
      Mg2+ accumulation. The combined stresses of salt and drought had a greater
      alleviation on the inhibition of dry weight caused by B than individual salt and
      drought. Besides, the combined stresses of salt and drought also enhanced B
      uptake and inhibited B transport. The results indicate that salt, drought, and
      the combined stresses of salt and drought all can alleviate B toxicity in P.
      tenuiflora, the main mechanism of which is the restriction of B and Na+ uptake
      caused by salt and drought. The combined stresses of salt and drought have a
      greater effect on B toxicity than individual salt and drought.

PMID- 29653374
TI  - The central role of hydrogen sulfide in plant responses to toxic metal stress.
AB  - With the increase of industrial wastes, sewage irrigation, chemical fertilizers
      and pesticides, metal contamination is increasingly serious. How to reduce the
      environmental risk has become a compelling problem in cultivated land. As a
      gaseous signal molecule, hydrogen sulfide (H2S) is involved in multiple plant
      responses to toxic metal stress. Metal stress rapidly triggers endogenous H2S
      production and exogenous H2S alleviates metal toxicity in plants. To elucidate
      the role of H2S in metal tolerance, the physiological and molecular mechanisms of
      H2S in alleviating metal toxicity is necessary to be reviewed. Here, the latest
      progress on endogenous H2S metabolism and the role of H2S in plant responses to
      toxic metal stress were summarized and discussed. The mechanisms of exogenous H2S
      in alleviating metal toxicity is proposed.

PMID- 29653375
TI  - Feeling fat in eating disorders: Testing the unique relationships between feeling
      fat and measures of disordered eating in anorexia nervosa and bulimia nervosa.
AB  - Although widely discussed in theories of eating disorders, the experience of
      "feeling fat" in this population has received little research attention. This
      study tested the unique relationships between feeling fat and measures of
      problematic eating behaviours and attitudes. Data were analysed from individuals
      with anorexia nervosa (AN; n = 123) and bulimia nervosa (BN; n = 51).
      Correlations revealed considerable unshared variance between feeling fat and
      shape and weight over-evaluation and depressive symptoms. Moreover, when over
      evaluation and depressive symptoms were controlled, feeling fat predicted unique
      variance in restraint and eating concerns. Findings offer some support for the
      idea that feeling fat is a distinct and important component of body image
      concerns in eating disorders. Further research that develops a standardized
      measure of feeling fat is required. Further research that examines whether
      feeling fat is an important treatment mechanism is also needed.

PMID- 29653376
TI  - Cue discriminability predicts instrumental conditioning.
AB  - Charting mental acts that succeed or fail under unconscious instances of
      cognition informs debates on the nature and potential functions of consciousness.
      A prominent method to exclude conscious contributions to cognition is to render
      visual stimuli unconscious by short and pattern-masked presentations. Here, we
      explore a combination of visual masking and pixel noise added to visual stimuli
      as a method to adapt discriminability in a fine-grained fashion to subject- and
      stimulus-specific estimates of perceptual thresholds. Estimates of the amount of
      pixel noise corresponding to perceptual thresholds are achieved by psychometric
      adaptive algorithms in an identification task. Afterwards, the feasibility of
      instrumental conditioning is tested at four levels of cue discriminability
      relative to previously acquired estimates of perceptual thresholds. In contrast
      to previous reports (Pessiglione et al., 2008), no evidence for the feasibility
      of instrumental condition was gathered when contributions of conscious cognition
      were excluded.

PMID- 29653377
TI  - Audio-visual sensory deprivation degrades visuo-tactile peri-personal space.
AB  - Self-perception is scaffolded upon the integration of multisensory cues on the
      body, the space surrounding the body (i.e., the peri-personal space; PPS), and
      from within the body. We asked whether reducing information available from
      external space would change: PPS, interoceptive accuracy, and self-experience.
      Twenty participants were exposed to 15 min of audio-visual deprivation and
      performed: (i) a visuo-tactile interaction task measuring their PPS; (ii) a
      heartbeat perception task measuring interoceptive accuracy; and (iii) a series of
      questionnaires related to self-perception and mental illness. These tasks were
      carried out in two conditions: while exposed to a standard sensory environment
      and under a condition of audio-visual deprivation. Results suggest that while PPS
      becomes ill defined after audio-visual deprivation, interoceptive accuracy is
      unaltered at a group-level, with some participants improving and some worsening
      in interoceptive accuracy. Interestingly, correlational individual differences
      analyses revealed that changes in PPS after audio-visual deprivation were related
      to interoceptive accuracy and self-reports of "unusual experiences" on an
      individual subject basis. Taken together, the findings argue for a relationship
      between the malleability of PPS, interoceptive accuracy, and an inclination
      toward aberrant ideation often associated with mental illness.

PMID- 29653378
TI  - Possible origins of consciousness in simple control over "involuntary"
      neuroimmunological action.
AB  - The origin(s) and purpose(s) of consciousness continue to be fervently debated by
      neuroscientists. A recent unconventional hypothesis put forth by Morsella et al.
      suggests the primary function of consciousness is the integration, selection, and
      execution of advantageous lower-level voluntary skeletal muscle behavior on
      surrounding external environments. However, at main issue is whether more
      precise, adaptable voluntary skeletal motor action, and therefore the
      corresponding workings of consciousness, first emerged and evolved in animals to
      exert control over external environments or internal ones regulated by less
      flexible autonomic function. Using the example of voluntary immunomodulation, one
      can identify the strengths and weaknesses of either rationale. For instance,
      highly trained meditative techniques for immunomodulation more-or-less conform to
      Morsella et al.'s assumptions on higher-level indirect conscious control of
      autonomic function. Whereas, untrained skeletal motor resolution of infection
      related approach-avoidance conflicts support conclusions contrary to those of
      Morsella et al. In such cases, primitive voluntary changes in host respiration
      rate and volume may selectively facilitate/inhibit acute autonomic
      psychophysiological stress responses to pathogen insult. This and other types of
      scenarios predictably give evolutionary and ecological rise to self-awareness of
      (visceral) internal states as well as to voluntary regulation of internal state
      action conflicts.

PMID- 29653379
TI  - Enhanced erythrocyte antioxidant status following an 8-week aerobic exercise
      training program in heavy drinkers.
AB  - Alcohol-induced oxidative stress is involved in the development and progression
      of various pathological conditions and diseases. On the other hand, exercise
      training has been shown to improve redox status, thus attenuating oxidative
      stress-associated disease processes. The purpose of the present study was to
      evaluate the effect of an exercise training program that has been previously
      reported to decrease alcohol consumption on blood redox status in heavy drinkers.
      In a non-randomized within-subject design, 11 sedentary, heavily drinking men
      (age: 30.3 +/- 3.5 years; BMI: 28.4 +/- 0.86 kg/m2) participated first in a
      control condition for 4 weeks, and then in an intervention where they completed
      an 8-week supervised aerobic training program of moderate intensity (50-60% of
      the heart rate reserve). Blood samples were collected in the control condition
      (pre-, post-control) as well as before, during (week 4 of the training program),
      and after intervention (week 8 of the training program). Samples were analyzed
      for total antioxidant capacity (TAC), thiobarbituric acid reactive substances
      (TBARS), protein carbonyls (PC), uric acid (UA), bilirubin, reduced glutathione
      (GSH), and catalase activity. No significant change in indices of redox status in
      the pre- and post-control was observed. Catalase activity increased (p < 0.05)
      after 8 weeks of intervention compared to week 4. GSH increased (p < 0.05) after
      8 weeks of intervention compared to the control condition and to week 4 of
      intervention. TAC, UA, bilirubin, TBARS, and PC did not significantly change at
      any time point. Moreover, concentrations of GSH, TBARS, and catalase activity
      negatively correlated with alcohol consumption. In conclusion, an 8-week aerobic
      training program enhanced erythrocyte antioxidant status in heavy drinkers,
      indicating that aerobic training may attenuate pathological processes caused by
      alcohol-induced oxidative stress.

PMID- 29653380
TI  - Fibroblast populated collagen lattices exhibit opposite biophysical conditions by
      fibrin or hyaluronic acid supplementation.
AB  - Fibrin and hyaluronic acid are important components of the provisional wound
      matrix. Through interactions with fibroblasts, they provide biophysical cues that
      regulate the viscoelastic properties of the extracellular matrix. To understand
      the roles of fibrin and hyaluronic acid in a collagenous environment, we used
      fibroblast populated collagen lattices (collagen, collagen-fibrin, and collagen
      hyaluronic acid). Compared with collagen and collagen-hyaluronic acid cultures,
      collagen-fibrin cultures showed less contraction, which is correlated with
      increased elastic (G') and complex (|G*|) moduli, and reduced proportions of
      dendritic fibroblasts, despite increased alphav integrin expression. Stiffness
      decreased during culture in collagen-fibrin environment, meanwhile phase shift
      (delta) values increased, clearly associated with the rise in fibrinolytic and
      gelatinolytic activities. These processes changed the viscoelastic properties of
      the system toward G' and |G*| values observed on day 5 in collagen cultures.
      Although less collagen turnover was observed in collagen-fibrin cultures than in
      collagen and collagen-hyaluronic acid cultures, collagen neosynthesis was
      apparently insufficient to contribute to the overall viscoelastic properties of
      the system. Collagen-hyaluronic acid cultures showed very limited changes during
      time. Firstly, they exhibited the highest delta values, suggesting an increase in
      the viscous behavior due to the hygroscopic properties of hyaluronic acid. These
      results showed that fibrin and hyaluronic acid not only affect differently the
      viscoelastic properties of the culture, they can tune fibroblastic activity by
      regulating cell attachment and extracellular matrix remodeling.

PMID- 29653381
TI  - Swelling of fiber-reinforced soft tissues is affected by fiber orientation, fiber
      stiffness, and lamella structure.
AB  - Native and engineered fiber-reinforced tissues are composites comprised of stiff
      collagen fibers embedded within an extrafibrillar matrix that is capable of
      swelling by absorbing water molecules. Tissue swelling is important for
      understanding stress distributions between collagen fibers and extrafibrillar
      matrix, as well as for understanding mechanisms of tissue failure. The swelling
      behavior of fiber-reinforced tissues in the musculoskeletal system has been
      largely attributed to the glycosaminoglycan content. Recent work demonstrated
      anisotropy in the swelling response of the annulus fibrosus in the intervertebral
      disc. It is well known that collagen fiber orientation affects elastic behavior,
      but the effect of collagen fiber network on tissue swelling behavior is not well
      understood. In this study, we developed three series of models to evaluate the
      effect of collagen fiber orientation, fiber network architecture (i.e., single or
      multi-fiber families within a layer), and fiber stiffness on bulk tissue
      swelling, which was simulated by describing the extrafibrillar matrix as a
      triphasic material, as proposed by Lai et al. Model results were within one
      standard deviation of reported mean values for changes in tissue volume, width,
      and thickness under free swelling conditions. The predicted swelling response of
      single-fiber family structures was highly dependent on fiber orientation and the
      number of lamellae in the bulk tissue. Moreover, matrix swelling resulted in
      tissue to twist, which reduced fiber deformations, demonstrating a balance
      between fiber deformation and matrix swelling. Large changes in fiber stiffness
      (20 * increase) had a relatively small effect on tissue swelling (~ 2% decrease
      in swelling). In conclusion, fiber angle, fiber architecture (defined as single-
      versus multiple fiber families in a layer), and the number of layers in a single
      fiber family structure directly affected tissue swelling behavior, including
      fiber stretch, fiber reorientation, and tissue deformation. These findings
      support the need to develop computational models that closely mimic the native
      architecture in order to understand mechanisms of stress distributions and tissue
      failure.

PMID- 29653382
TI  - Acute exposure of white-tailed deer cortical bone to Staphylococcus aureus did
      not result in reduced bone stiffness.
AB  - Staphylococcus aureus (S. aureus) is the main source of osteomyelitis in adults.
      The end-result of untreated osteomyelitis is bone necrosis and distraction of
      bone structure. While bone tissue can heal and remodel its structure to
      ameliorate its mechanical properties, so far no study has tested the mechanical
      properties of cortical bone tissue exposed to S. aureus. With the increase usage
      of bone banks as a source of bone graft supply, it is important to screen for any
      possible pathology that may affect the bone graft success to function normally in
      the receiving patient. This study tested the effect of acute exposure to S.
      aureus on cortical bone stiffness. We have postulated that the incubation of
      cortical bone with S. aureus for 48 h will result in a significant decrease in
      bone stiffness. Sixty-five bone cubes (2 * 2 * 2 mm) were prepared from the
      cranial and caudal aspects of four white-tailed deer mid-diaphysis humeri. First,
      all bone samples were tested to determine their stiffness in the three principle
      orientations (axial, radial and transverse). Next, bone samples were incubated
      for 48 h with S. aureus (32 cubes, experimental group) or with sterile distilled
      water (33 cubes, control group). Finally, all cubes were mechanically tested
      again and each stiffness value was compared to the original value obtained from
      the same cube. Our results revealed that overall, acute exposure to S. aureus did
      not significantly decrease bone stiffness and thus our working hypothesis could
      not be supported. Therefore, our findings support the current tissue collection
      screening methods employed by bone-graft banks.

PMID- 29653383
TI  - Characterizing fretting damage in different test media for cardiovascular device
      durability testing.
AB  - In vitro durability tests of cardiovascular devices are often used to evaluate
      the potential for fretting damage during clinical use. Evaluation of fretting
      damage is important because severe fretting can concentrate stress and lead to
      the loss of structural integrity. Most international standards call for the use
      of phosphate buffered saline (PBS) for such tests although there has been little
      evidence to date that the use of PBS is appropriate in terms of predicting the
      amount of fretting damage that would occur in vivo. In order to determine an
      appropriate test media for in vitro durability tests where fretting damage is
      being evaluated, we utilized an in vitro test that is relevant to cardiovascular
      devices both in terms of dimensions and materials (nitinol, cobalt-chromium, and
      stainless steel) to characterize fretting damage in PBS, deionized water (DIW),
      and heparinized porcine blood. Overall, tests conducted in blood were found to
      have increased levels of fretting damage over tests in DIW or PBS, although the
      magnitude of this difference was smaller than the variability for each test
      media. Tests conducted in DIW and PBS led to mostly similar amounts of fretting
      damage with the exception of one material combination where DIW had greatly
      reduced damage compared to PBS and blood. Differences in fretting damage among
      materials were also observed with nitinol having less fretting damage than
      stainless steel or cobalt-chromium. In general, evaluating fretting damage in PBS
      or DIW may be appropriate although caution should be used when selecting test
      media and interpreting results given some of the differences observed across
      different materials.

PMID- 29653384
TI  - Acute toxicity and associated mechanisms of four strobilurins in algae.
AB  - Strobilurins have been reported highly toxic to non-target aquatic organisms but
      few illustrated how they cause toxic effects on algae. This study investigated
      the acute toxicity of Kresoxim-methy (KRE), Pyraclostrobin (PYR), Trifloxystrobin
      (TRI) and Picoxystrobin (PIC) on two algae and their toxicity mechanisms. Four
      strobilurins showed lower toxic effects on Chlorella pyrenoidsa but higher on
      Chlorella vulgaris. bc1 complex activities in C. vulgaris were significantly
      inhibited by all strobilurins, suggesting bc 1 complex might be the target of
      strobilurin toxicity in algae. Moreover, SOD, CAT and POD activities were
      significantly up-regulated by all doses of KRE, PYR and PIC. In contrast, low
      concentrations of TRI stimulated SOD and POD activities but highest concentration
      significantly inhibited those activities. Comet assays showed damaged DNA in C.
      vulgaris by four strobulirins, suggesting their potential genotoxic threats to
      algae. The results illustrated acute toxicity by strobulirins on algae and their
      possible toxicity mechanisms.

PMID- 29653385
TI  - Histological and ultrastructural alterations of the Italian newt (Lissotriton
      italicus) skin after exposure to ecologically relevant concentrations of
      nonylphenol ethoxylates.
AB  - Nonylphenol ethoxylates (NPEs) are well known endocrine disruptors. Widespread
      environmental contamination from NPEs is an issue of great concern. Despite
      amphibians are often exposed to such contaminants, very little attention has been
      dedicated to this vertebrate group. No information is available on the effects of
      NPEs onto the amphibian skin and only few reports have been conducted on fish.
      Here, histological and ultrastructural modifications of the skin have been
      evaluated in the Italian newt Lissotriton italicus. After a short-term exposure
      to two ecologically relevant concentrations of NP, severe pathological
      alterations, both dose and time-dependent, have been observed. The main effects
      were an increased mucous secretion, the dilation of the endomembrane, the
      wrinkling of the epidermal surface, the appearance of tubercles, the increased
      cellular turnover, continuous shedding processes. Some of the described skin
      alterations can easily interfere with physiological functions, such as
      osmoregulation and body protection, with detrimental consequences for the
      amphibian populations.

PMID- 29653386
TI  - Synergistic effects of resveratrol and melatonin on in vitro maturation of
      porcine oocytes and subsequent embryo development.
AB  - Resveratrol and melatonin are known for their antioxidant properties and have
      various biological activities. The fact that they exhibit possible synergistic
      effects in phytomedicine researches suggests the use of a combination of these
      agents to promote porcine in vitro maturation (IVM) of oocytes. Therefore, we
      investigated the effects of resveratrol and/or melatonin on this process; cumulus
      oocyte complexes underwent IVM culture with four different conditions (control,
      resveratrol, melatonin or their combination). Cumulus expansion, oocyte nuclear
      maturation and subsequent embryo development after parthenogenetic activation
      (PA) and somatic cell nuclear transfer (SCNT) were evaluated. In experiment 1,
      all treatment groups significantly increased the proportion of complete cumulus
      expansion (degree 4) compared to the control, showing no difference among the
      treatment groups (P = 0.30). In experiment 2, oocytes matured with resveratrol
      and the combination had significantly higher metaphase-II (MII) rates than the
      control and melatonin groups, showing the highest (P < 0.05) MII rates in the
      combination group. In experiment 3, all treatment groups significantly increased
      blastocyst formation rates and total blastocyst cell numbers after PA compared to
      the control, but especially the combination showed the highest (P < 0.05) total
      cell numbers. In experiment 4, we selected the combination as the optimal
      condition and used this IVM system prior to SCNT. The combination treatment
      showed a significant (P < 0.05) increase in blastocyst formation rate and total
      cell numbers after SCNT. In conclusion, our results suggest that the combination
      of resveratrol and melatonin supported a synergistic increase in oocyte nuclear
      maturation and total cell numbers of PA blastocysts and improved the development
      of SCNT embryos.

PMID- 29653387
TI  - Bovine uterus-derived exosomes improve developmental competence of somatic cell
      nuclear transfer embryos.
AB  - Exosomes widely exist in various tissues and body fluids, including blood, tissue
      fluid, and urine. In the present study, exosomes were first isolated from the
      early luteal phase uterus and confirmed through morphological examination,
      immunofluorescence (IF) staining of special membrane antigen, and Western blot.
      The effects of exosomes on the developmental competence of somatic cell nuclear
      transfer (SCNT) embryos were investigated. Transmission electron microscopy
      results showed that the isolated exsomes were spherical particles with a 50 nm
      150 nm diameter. Immunostaining showed that the surface of these isolated
      particles were CD9 positive, which was confirmed using Western blot.
      Supplementing SCNT embryos with these isolated exsomes on day 4 of culture
      significantly increased the blastocyst formation rate (31% vs. 34%, 40.3%, and
      34.3%) and hatching rate (30.3% vs. 33.3%, 40.7%, and 35%) in comparison with the
      non-supplementation (control), and day 3 and day 5 supplementation groups.
      Blastocysts from the exsome supplementation groups showed higher inner cell
      mass/trophectoderm cell ratio (48% vs 37.9%) and lower apoptosis index (2.1% vs
      6.5%) than the control group. The gene expression analysis of the blastocysts
      also showed that the exsomes supplementation significantly enhanced the
      expression levels of IFNT and acrogranin and decreased the expression levels of
      HSP70, BAX and BIP. In conclusion, the present study indicated that the early
      luteal phase uterus secretes exosomes, which might play important roles in the
      development of SCNT embryos.

PMID- 29653388
TI  - Synchronization treatments previous to natural breeding anticipate and improve
      the pregnancy rate of postpartum primiparous beef cows.
AB  - Timed AI has become a potential tool to bypass postpartum acyclicity, yet only a
      small percentage of the world bovine herd is inseminated. Most females are still
      subjected to bull mating; therefore, the frequent occurrence of postpartum
      anestrus may compromise their reproductive efficiency. Thus, the aim of this
      study was to develop an approach that allows the early conception of postpartum
      primiparous beef cows that are exposed to natural breeding (NB). For this
      purpose, 350 primiparous Nelore cows 35-65 d postpartum were allocated into three
      groups: Control (no hormonal treatment), TNB (hormonal protocol for timed-NB
      without equine chorionic gonadotropin; eCG) and TNB + eCG (hormonal protocol for
      TNB with eCG) groups. The protocol for TNB consisted of the insertion of a 1-g
      progesterone device and the intramuscular (IM) administration of 2 mg estradiol
      benzoate on D-9 (nine days before bull exposure), followed by device removal and
      the administration of 1 mg estradiol cypionate IM on D0. An additional 300 IU of
      eCG was given only to TNB + eCG cows. All cows were exposed to bull mating from
      D0 to D105. Pregnancy was checked by ultrasonography every 50 d, gestational age
      was estimated, and the number of new gestations every 21-d cycle (P21, P42, P63,
      P84 and P105) was predicted. Control cows had lower pregnancy at P21 (5.7%c,
      7/123) than TNB (30.4%b, 35/115) and TNB + eCG (51.8%a, 58/112; P = 0.001) cows.
      Pregnancy rate increased across P42, P63 and P84 (P = 0.001) but remained higher
      for TNB + eCG cows. Regarding time to conception, the TNB + eCG cows achieved a
      greater than 50% pregnancy rate within the first days after bull exposure, while
      the TNB and Control cows took more than 40 d and 90 d to achieve 50% pregnancy
      rates, respectively. At the end of the breeding season (BS), TNB + eCG cows had a
      21% higher pregnancy rate than the Control cows and a 16% higher rate than the
      TNB cows. The probability of conceiving increased 1.5-fold for cows treated with
      TNB (P = 0.0079) and 2.2-fold for cows additionally treated with eCG (P <
      0.0001). The average interval between the onset of the BS and conception was
      reduced (P < 0.0001) for the TNB + eCG cows (26.5 +/- 3.8c) compared to the TNB
      (35.7 +/- 4.1b) and Control (64.7 +/- 3.9a days) cows. Thus, the use of TNB,
      especially when associated with eCG, efficiently improved the early conception of
      postpartum primiparous beef cows after exposure to NB. The increased number of
      cows conceiving early in the BS is crucial to improve reproductive efficiency by
      reducing the interval between parturitions and improving the number of pregnant
      cows at the end of BS, thus resulting in greater farm income.

PMID- 29653389
TI  - How does the microbial load affect the quality of equine cool-stored semen?
AB  - Contaminating bacteria present in stallion ejaculates may compromise sperm
      quality during storage. Different procedures have been used to reduce the load of
      microorganisms in semen and avoid bacterial growth during storage. The aims of
      this study were: 1) to evaluate different techniques to eliminate bacteria in
      semen 2) to study the relationship between total microflora load (TML) and ROS
      production; and 3) to determine if TML affects the functionality of cool-stored
      sperm. Ejaculates from 11 stallions were split and processed in 3 ways: A.
      extended semen; B. conventional centrifuged semen, and C. Single layer
      centrifugation through Androcoll-E (SLC). All samples were preserved in INRA 96
      at 5  degrees C for 72 h. Aliquots from native semen and from different
      treatments were taken for bacteriological analysis at T0, T24, T48 and T72h of
      storage and Total microbial load (TML: CFU (colony-forming units/ml) was
      calculated. The ROS production (dichlorodihydrofluorescein diacetate for H2O2,
      dihydroethidium for superoxide anion and CellROX deep red for total ROS),
      viability (YO-PRO-1-Ethidium) and lipid peroxidation (BODIPY-C11) were assessed
      by flow cytometry, and motility by CASA. The bacteria isolated were
      Corynebacterium spp, Arcanobacterium spp, Bacillus spp, Dermobacter,
      Staphylococcus spp, Streptococcus spp, Penicilium spp. TML of semen showed
      correlations with live sperm (r: -0.771), dead sperm (r: 0.580), H2O2 production
      (r: 0.740), and total ROS production (CellROX (+)) (r: -0.607), Total motility
      (r: 0.587), Progressive motility (r: -0.566), VCL (r: -0.664), VSL (r: -0,569),
      VAP (r: -0.534) (p <= 0.05). SLC removed 99.34% of the microbial load, which was
      assicated with a significanlty reduced H2O2 production (p <= 0.05). However, only
      samples treated with Androcoll-E had a higher total ROS production (CellROX +) (p
      <= 0.05). These results suggest that CellROX stain probably identifies superoxide
      production rather than H2O2 and this higher superoxide production may reflect an
      intense sperm functionality. The bacterial load increased the production of H2O2
      in cool-stored semen which was associated with lower tolerance to refrigeration.
      SLC was the sperm processing technique that was most efficient at removing
      bacteria, reducing H2O2 production and selecting the most functional sperm.

PMID- 29653390
TI  - Fondaparinux versus nadroparin for thromboprophylaxis following minimally
      invasive esophagectomy: A randomized controlled trial.
AB  - BACKGROUND: The methodology of thromboprophylaxis post minimally invasive
      esophagectomy (MIE) is unclear. Thus, we compared the efficacy and safety of
      fondaparinux and nadroparin on the prophylaxis of venous thromboembolism (VTE)
      after MIE. MATERIALS AND METHODS: We conducted a randomized, double-blind,
      treatment-controlled study. Consecutive patients undergoing MIE randomly received
      a single dose of either nadroparin 2850 AxaIU (Group H) or fondaparinux 2.5 mg
      (Group F) daily. We used ultrasonography to identify deep vein thrombosis (DVT)
      on postoperative day 7. The coagulation status was examined using
      thromboelastography (TEG) prior to and at 0, 24, 48, and 72 h after the
      operation. Bleeding events were recorded during anticoagulation therapy and
      analysis was performed on an intention-to-treat basis. RESULTS: We randomly
      assigned the patients to Group H (n = 57) or Group F (n = 59). Symptomatic or
      asymptomatic DVT was identified in seven patients in Group H and one patient in
      Group F (12.28% vs. 1.69%, p = 0.031). Pulmonary embolism developed in one
      patient in Group H, and the VTE incidence was significantly lower in Group F than
      Group H (1.69% vs. 14.04%, RR: 0.121, 95% CI: 0.016-0.935, p = 0.016). TEG
      analysis showed a more inhibited coagulation profile of Group F compared with
      Group H reflected by the significantly prolonged R time at 48 h and 72 h after
      operation (6.8 +/- 2.2 min vs. 8.4 +/- 2.7 min, p = 0.005; 7.1 +/- 1.6 min vs.
      9.2 +/- 3.7 min, p = 0.002). Bleeding events were not recorded in either group.
      CONCLUSIONS: Fondaparinux could provide similar efficacy and safety in
      postoperative thromboprophylaxis following MIE compared with nadroparin.

PMID- 29653391
TI  - Sources of particulate matter in China: Insights from source apportionment
      studies published in 1987-2017.
AB  - Particulate matter (PM) in the atmosphere has adverse effects on human health,
      ecosystems, and visibility. It also plays an important role in meteorology and
      climate change. A good understanding of its sources is essential for effective
      emission controls to reduce PM and to protect public health. In this study, a
      total of 239 PM source apportionment studies in China published during 1987-2017
      were reviewed. The documents studied include peer-reviewed papers in
      international and Chinese journals, as well as degree dissertations. The methods
      applied in these studies were summarized and the main sources in various regions
      of China were identified. The trends of source contributions at two major cities
      with abundant studies over long-time periods were analyzed. The most frequently
      used methods for PM source apportionment in China are receptor models, including
      chemical mass balance (CMB), positive matrix factorization (PMF), and principle
      component analysis (PCA). Dust, fossil fuel combustion, transportation, biomass
      burning, industrial emission, secondary inorganic aerosol (SIA) and secondary
      organic aerosol (SOA) are the main source categories of fine PM identified in
      China. Even though the sources of PM vary among seven different geographical
      areas of China, SIA, industrial, and dust emissions are generally found to be the
      top three source categories in 2007-2016. A number of studies investigated the
      sources of SIA and SOA in China using air quality models and indicated that
      fossil fuel combustion and industrial emissions were the most important sources
      of SIA (total contributing 63.5%-88.1% of SO42-, and 47.3%-70% NO3-), and
      agriculture emissions were the dominant source of NH4+ (contributing 53.9%-90%).
      Biogenic emissions were the most important source of SOA in China in summer,
      while residential and industrial emissions were important in winter. Long-term
      changes of PM sources at two megacities of Beijing and Nanjing indicated that the
      contributions of fossil fuel and industrial sources have been declining after
      stricter emission controls in recent years. In general, dust and industrial
      contributions decreased and transportation contributions increased after 2000.
      PM2.5 emissions are predicted to decline in most regions during 2005-2030, even
      though the energy consumptions except biomass burning are predicted to continue
      to increase. Industrial, residential, and biomass burning sources will become
      more important in the future in the businuess-as-usual senarios. This review
      provides valuable information about main sources of PM and their trends in China.
      A few recommendations are suggested to further improve our understanding the
      sources and to develop effective PM control strategies in various regions of
      China.

PMID- 29653392
TI  - Electrolyzed water and mild-thermal processing of Atlantic salmon (Salmo salar):
      Reduction of Listeria monocytogenes and changes in protein structure.
AB  - This study investigated the effect of different electrolyzed water (EO)
      solutions, including acidic electrolyzed water (AEW) and neutral electrolyzed
      water (NEW), alone and in combination with mild thermal processing (50, 55, 60,
      65  degrees C) at different exposure times (2, 6, 10 min) on the reduction of
      Listeria monocytogenes on Atlantic salmon fillets. The effects of the EO water
      solutions on cell wall structures of L. monocytogenes and on the secondary
      structure of salmon protein were studied using Fourier Transform Infra-Red (FTIR)
      spectroscopy. Temperature and time significantly influenced the efficacy of the
      AEW and NEW. NEW has stronger antimicrobial properties as compared to AEW. The
      highest bacterial reduction was observed at 65  degrees C after 10 min for salmon
      treated with NEW, with a 5.6 log10 CFU/g reduction. Spectral features show that
      the secondary protein structures in salmon muscle treated with NEW were less
      affected than tissue treated with AEW as shown in a PCA model. In addition, the
      FTIR spectra for L. monocytogenes showed that the NEW and AEW affected cell wall
      properties differently; this might be due to the form of available chlorine in
      NEW and AEW and to AEW having a lower pH. In general, NEW showed better
      antimicrobial properties, particularly when combined with mild thermal processing
      than AEW and also caused less alteration in protein structure. The findings of
      this study may be used to improve the quality and safety of cured and smoked
      ready-to-eat fish products.

PMID- 29653393
TI  - Antifungal activity and action mechanisms of yeasts isolates from citrus against
      Penicillium italicum.
AB  - Penicillium italicum (Blue mold) is a major postharvest disease of citrus. An
      alternative to controlling the disease is through the use of yeasts. The purpose
      of the present study was to screen effective yeast antagonists against P.
      italicum, isolated from soil, leaves, flowers, and citrus fruits, to assess the
      action mechanisms of the yeast isolates that were demonstrated to be effective
      for biocontrol, and to identify the most effective yeast isolates for the
      biocontrol of blue mold. The in vitro assays showed that six yeast strains
      inhibited up to 90% of the pathogen's mycelial growth. In vivo assays, evaluating
      the incidence of blue mold on sweet oranges, the strains ACBL-04, ACBL-05, ACBL
      10 and ACBL-11 were effective, demonstrating the potential for the blue mold
      control when preventively applied, whereas the ACBL-08 strain showed a high
      potential to preventive and curative applications. Additional studies on the
      modes of action of these yeast strains showed that most of the evaluated yeast
      strains did not produce antifungal substances, in sufficient quantities to
      inhibit the pathogen growth. Competition for nutrients was not a biocontrol
      strategy used by the yeast strains. The 'killer' activity might be the main
      action mechanism involved in P. italicum biocontrol. This study indicated that
      the multiple modes of action against the pathogen presented by yeasts may explain
      why these strains provided P. italicum control under in vitro and in vivo
      conditions. However, further studies in future might be able to elucidate the
      'killer' activity and its interaction with pathogen cells and the bioproduct
      production using Candida stellimalicola strains for control postharvest diseases.

PMID- 29653394
TI  - Generation of Duchenne muscular dystrophy patient-specific induced pluripotent
      stem cell line lacking exons 45-50 of the dystrophin gene (IITi001-A).
AB  - Duchenne muscular dystrophy (DMD) is an X-linked progressive muscle degenerative
      disease caused by mutations in the dystrophin gene. We generated induced
      pluripotent stem cells (iPSCs) from a 13-year-old male patient carrying a
      deletion mutation of exons 45-50; iPSCs were subsequently differentiated into
      cardiomyocytes. iPSCs exhibit expression of the pluripotent markers (SOX2, NANOG,
      OCT4), differentiation capacity into the three germ layers, normal karyotype,
      genetic identity to the skin biopsy dermal fibroblasts and the patient-specific
      dystrophin mutation.

PMID- 29653395
TI  - Learning physical parameters from dynamic scenes.
AB  - Humans acquire their most basic physical concepts early in development, and
      continue to enrich and expand their intuitive physics throughout life as they are
      exposed to more and varied dynamical environments. We introduce a hierarchical
      Bayesian framework to explain how people can learn physical parameters at
      multiple levels. In contrast to previous Bayesian models of theory acquisition
      (Tenenbaum, Kemp, Griffiths, & Goodman, 2011), we work with more expressive
      probabilistic program representations suitable for learning the forces and
      properties that govern how objects interact in dynamic scenes unfolding over
      time. We compare our model to human learners on a challenging task of estimating
      multiple physical parameters in novel microworlds given short movies. This task
      requires people to reason simultaneously about multiple interacting physical laws
      and properties. People are generally able to learn in this setting and are
      consistent in their judgments. Yet they also make systematic errors indicative of
      the approximations people might make in solving this computationally demanding
      problem with limited computational resources. We propose two approximations that
      complement the top-down Bayesian approach. One approximation model relies on a
      more bottom-up feature-based inference scheme. The second approximation combines
      the strengths of the bottom-up and top-down approaches, by taking the feature
      based inference as its point of departure for a search in physical-parameter
      space.

PMID- 29653397
TI  - When some triggers a scalar inference out of the blue. An electrophysiological
      study of a Stroop-like conflict elicited by single words.
AB  - Some studies in experimental pragmatics have concluded that scalar inferences
      (e.g., 'some X are Y' implicates 'not all X are Y') are context-dependent
      pragmatic computations delayed relative to semantic computations. However, it
      remains unclear whether strong contextual support is necessary to trigger such
      inferences. Here we tested if the scalar inference 'not all' triggered by some
      can be evoked in a maximally neutral context. We investigated event-related
      potential (ERP) amplitude modulations elicited by Stroop-like conflicts in
      participants instructed to indicate whether strings of letters were printed with
      all their letters in upper case or otherwise. In a randomized stream of non-words
      and distractor words, the words all, some and case were either presented in
      capitals or they featured at least one lower case letter. As expected, we found a
      significant conflict-related N450 modulation when comparing e.g., 'aLl' with
      'ALL'. Surprisingly, despite the fact that most responses from the same
      participants in a sentence-picture verification task were literal, we also found
      a similar modulation when comparing 'SOME' with e.g., 'SoMe', even though SOME
      could only elicit such a Stroop conflict when construed pragmatically. No such
      modulation was found for e.g., 'CasE' vs. 'CASE' (neutral contrast). These
      results suggest that some can appear incongruent with the concept of 'all' even
      when contextual support is minimal. Furthermore, there was no significant
      correlation between N450 effect magnitude ('SOME' minus e.g., 'sOMe') and
      pragmatic response rate recorded in the sentence-picture verification task.
      Overall, this study shows for the first time that the pragmatic meaning of some
      can be accessed in a maximally neutral context, and thus, that the scalar
      inference 'not all' triggered by some should be construed as context-sensitive
      rather than context-dependent, that is, more or less salient and relevant
      depending on the context rather than entirely contingent upon it.

PMID- 29653396
TI  - Gut microbiota recovery and immune response in ampicillin-treated mice.
AB  - Ampicillin is applied in rodents to induce a temporarily depleted microbiota. To
      elucidate whether bacteria are just temporarily suppressed or fully eliminated,
      and how this affects the re-colonisation process, we compared the microbiota and
      immune system in conventionally housed untreated mice with newly weaned
      ampicillin treated mice subsequently housed in either a microbe containing
      environment or in an isolator with only host associated suppressed bacteria to
      recolonize the gut. Two weeks ampicillin treatment induced a seemingly germ-free
      state with no bacterial DNA to reveal. Four weeks after treatment caeca were
      still significantly enlarged in both treated groups, but bacteria re-appeared
      even in isolator housed mice. While some suppressed bacteria were able to recover
      and even dominate the community, the abundances and composition were far from the
      untreated mice and differed between isolator and conventional housing. The
      treatment reduced the innate cytokine expressions at least for three weeks after
      treatment, and had a non-lasting reducing impact on the regulatory T cells, and a
      more lasting impact on the natural killer T cells. We conclude that temporary
      ampicillin treatment suppresses the majority but does not eliminate all the gut
      microbiota members. The re-colonisation process is as such influenced by both
      suppressed host associated bacteria and by environmental bacteria. Treated mice
      do not re-obtain a complex gut microbiota comparable to untreated mice, and the
      immune response and gut morphology reflect this. This is a concern when comparing
      host parameters sensitive to microbial regulation after an antibiotic-induced
      temporarily "germ-free" state.

PMID- 29653398
TI  - Growth of symbolic number knowledge accelerates after children understand
      cardinality.
AB  - Children who achieve an early understanding of the cardinal value of number words
      (cardinal knowledge) have a superior understanding of the relations among
      numerals at school entry, controlling other factors (e.g., intelligence). We
      tested the hypothesis that this pattern emerges because an understanding of
      cardinal value jump starts children's learning of the relations among numerals.
      Across two years of preschool, the cardinal knowledge of 179 children (85 boys)
      was assessed four times, as was their understanding of the relative quantity of
      Arabic numerals and competence at discriminating nonsymbolic quantities. Children
      were more accurate on nonsymbolic than numeral comparisons before they understood
      cardinality, but showed more rapid growth for numeral than nonsymbolic
      comparisons once they understood cardinality. Moreover, and with the possible
      exception of very small numerals (<5), before they understood cardinality
      children were no better than chance in their numeral comparisons, but greatly
      exceeded chance once they understood cardinality. These patterns were independent
      of the age at which children became cardinal principle knowers and independent of
      intelligence, executive function, and preliteracy skills. More broadly, the
      results provide a developmental bridge between cardinal knowledge and school
      entry number knowledge.

PMID- 29653399
TI  - Contribution to the development of low frequency terahertz coherent Raman micro
      spectroscopy and microscopy.
AB  - We report the construction and characterization of a coherent Raman tabletop
      system utilizing a novel astigmatic optical focusing geometry, a broadband
      nanosecond optical parametric oscillator and volumetric Bragg filters assisting
      3CBCRS measuring system for the first time. In order to illustrate the
      versatility of the measurements and reveal the molecular information obtainable,
      two well-characterized chemicals were selected. Polarization sensitive epi
      detected 3CBCRS spectra of liquid CCl4 and calcite crystal were recorded and
      analyzed. An unexpected polarization dependence of the signals of the lowest
      frequency modes of CCl4 was observed. The 1122 third order susceptibility
      component was phase flipped. The non-resonant susceptibility normalized 1122
      component was found to be larger than the 1111 component for the lowest
      vibrational modes. This anomalous comportment was attributable to the anisotropy
      Raman tensor invariant in the third order nonlinear susceptibility tensor.

PMID- 29653400
TI  - Polychlorinated biphenyls and chlorinated paraffins in home-produced eggs from an
      e-waste polluted area in South China: Occurrence and human dietary exposure.
AB  - The levels of polychlorinated biphenyls (PCBs) and short/median-chain chlorinated
      paraffins (S/MCCPs) in 68 home-produced eggs collected in 2013 and 2016 from an
      electronic-waste (e-waste) site in South China were measured and the human
      dietary exposure to these two classes of contaminants via egg consumption was
      calculated. The levels of PCBs, SCCPs, and MCCPs varied from 236 to 8870 ng/g
      lipid weight (lw), 477 to 111,000 ng/g lw, and 125 to 91,100 ng/g lw,
      respectively. There are no significant differences in the levels of PCBs, SCCPs,
      and MCCPs between 2013 and 2016 (p > 0.05). The congener profiles of PCBs and
      MCCPs were similar to each other between 2013 and 2016; however, the homologue
      profiles of SCCPs were different. The Toxic Equivalent Quantities (TEQs) of ?DL
      PCBs and the levels of ?ICES-6 PCBs strongly exceeded the limits set by EU
      Regulation 1259/2011 (2.5 pg World Health Organization-TEQ2005 g-1 lw for DL
      ?PCBs and 40 ng/ g lw for ?ICES-6 PCBs). The estimated daily intakes (EDI) of
      PCBs, SCCPs, and MCCPs by adults and children ranged between 5.57 and 1100, 11.8
      and 11,900, and 3.62 and 11,400 ng/kg bw/d, respectively. PCBs pose serious
      health risks for local residents, especially for children, due to the high ratios
      of EDI (68% in 2013 and 70% in 2016 for adults and 100% for children) in excess
      of the exposure limits.

PMID- 29653401
TI  - Antibiotics and antibiotic resistance genes in global lakes: A review and meta
      analysis.
AB  - Lakes are an important source of freshwater, containing nearly 90% of the liquid
      surface fresh water worldwide. Long retention times in lakes mean pollutants from
      discharges slowly circulate around the lakes and may lead to high ecological risk
      for ecosystem and human health. In recent decades, antibiotics and antibiotic
      resistance genes (ARGs) have been regarded as emerging pollutants. The occurrence
      and distribution of antibiotics and ARGs in global freshwater lakes are
      summarized to show the pollution level of antibiotics and ARGs and to identify
      some of the potential risks to ecosystem and human health. Fifty-seven
      antibiotics were reported at least once in the studied lakes. Our meta-analysis
      shows that sulfamethoxazole, sulfamerazine, sulfameter, tetracycline,
      oxytetracycline, erythromycin, and roxithromycin were found at high
      concentrations in both lake water and lake sediment. There is no significant
      difference in the concentration of sulfonamides in lake water from China and that
      from other countries worldwide; however, there was a significant difference in
      quinolones. Erythromycin had the lowest predicted hazardous concentration for 5%
      of the species (HC5) and the highest ecological risk in lakes. There was no
      significant difference in the concentration of sulfonamide resistance genes (sul1
      and sul2) in lake water and river water. There is surprisingly limited research
      on the role of aquatic biota in propagation of ARGs in freshwater lakes. As an
      environment that is susceptible to cumulative build-up of pollutants, lakes
      provide an important environment to study the fate of antibiotics and transport
      of ARGs with a broad range of niches including bacterial community, aquatic
      plants and animals.

PMID- 29653402
TI  - Long-term exposure to airborne particulate matter and NO2 and prevalent and
      incident metabolic syndrome - Results from the Heinz Nixdorf Recall Study.
AB  - INTRODUCTION: Recently, epidemiological studies have found a link between air
      pollution (AP) and individual components of the metabolic syndrome (MetS), a
      condition predisposing to cardiometabolic diseases. However, very few studies
      have explored a possible association between air pollution and MetS. OBJECTIVE:
      We analyzed the effects of long-term exposure to airborne particulate matter and
      NO2 on prevalence and incidence of MetS. METHODS: We used data of the population
      based prospective Heinz Nixdorf Recall study (baseline 2000-2003) to investigate
      the association(s) between AP exposure and MetS prevalence at baseline (n = 4457)
      and MetS incidence at first follow-up visit (n = 3074; average follow-up: 5.1
      years). Mean annual exposure to size-fractioned particulate matter (PM10, PM2.5,
      PMcoarse, and PM2.5abs) and nitrogen dioxide (NO2) was assessed using a land use
      regression model. MetS was defined as central obesity plus two out of four
      additional risk factors (i.e., elevated triglycerides, reduced high-density
      lipoprotein cholesterol, elevated blood pressure or elevated plasma glucose). We
      estimated odds ratios (ORs) of MetS prevalence and incidence per interquartile
      range (IQR) of exposure, adjusting for demographic and lifestyle variables.
      RESULTS: We observed a MetS prevalence of 20.7% (n = 922) and an incidence of
      9.7% (n = 299). NO2 was positively associated with MetS prevalence, with an OR
      increase per IQR of 1.12 (95%-CI 1.02-1.24, IQR = 6.1 MUg/m3). PM10 and PM2.5
      were both borderline positively associated with MetS incidence, with ORs of 1.14
      (95%-CI 0.99-1.32, IQR = 2.1 MUg/m3) and 1.19 (95%-CI 0.98-1.44, IQR = 1.5
      MUg/m3) per IQR, respectively. CONCLUSION: In summary, we found a weak positive
      association between air pollution and MetS. The strongest and most consistent
      effects were observed between NO2 and prevalent MetS.

PMID- 29653403
TI  - Concurrent phone texting alters crossing behavior and induces gait imbalance
      during obstacle crossing.
AB  - Texting during walking has become a very common daily activity and could alter
      gait performance, especially during locomotion when additional visual attention
      is demanded, such as obstacle crossing. The purpose of this study was to examine
      biomechanical changes in obstructed gait characteristics while engaging in a
      phone texting activity. Gait analyses were performed on ten young healthy adults
      under the following two tasks: 1) walking and crossing an obstacle set at a 10%
      of the subject's height and 2) walking and crossing an obstacle while responding
      to a text message. Whole body motion data were collected with a 10-camera motion
      capture system. Our data demonstrated that a conservative gait pattern was
      adopted while performing texting when approaching and crossing over the obstacle,
      which was indicated by slower walking speeds and greater toe-obstacle clearances.
      This gait pattern was, however, accompanied by a greater body sway in the frontal
      plane during crossing, which could be an indication of perturbed gait balance
      control. Increased visual-attentional demand from a concurrent phone texting
      could negatively impact young pedestrians' safety during obstacle crossing.

PMID- 29653404
TI  - Static postural control among school-aged youth with Down syndrome: A systematic
      review.
AB  - BACKGROUND: Youth with Down syndrome are characterized by motor delays when
      compared to typically developing (TD) youth, which may be explained by a lower
      postural control or reduced postural tone. OBJECTIVE: In the present article, we
      summarize research comparing the static postural control, assessed by
      posturography, between youth with Down syndrome and TD youth. METHODS: A
      systematic literature search was performed in 10 databases and seven studies,
      published between 2001 and 2017, met our inclusion criteria. RESULTS: Based on
      the present reviewed findings, it is impossible to conclude that children with
      Down syndrome present significantly lower static postural control compared to TD
      children. In contrast, findings showed that adolescents with Down syndrome tended
      to present significantly lower static postural control compared to TD adolescents
      when visual and plantar cutaneous inputs were disturbed separately or
      simultaneously. CONCLUSION: The present findings should be interpreted with
      caution given the limitations of the small number of reviewed studies. Therefore,
      the static postural control among youth with Down syndrome should be further
      investigated in future rigorous studies examining the contribution of a range of
      sensory information.

PMID- 29653405
TI  - Modeling margin of stability with feet in place following a postural
      perturbation: Effect of altered anthropometric models for estimated extrapolated
      centre of mass.
AB  - BACKGROUND: Maintaining the centre of mass (CoM) of the body within the base of
      support is a critical component of upright balance; the ability to accurately
      quantify balance recovery mechanisms is critical for many research teams.
      RESEARCH QUESTION: The purpose of this study was to investigate how exclusion of
      specific body segments in an anthropometric CoM model influenced a dynamic
      measure of postural stability, the margin of stability (MoS), following a support
      surface perturbation. METHODS: Healthy young adults (n = 10) were instrumented
      with kinematic markers and a safety harness. Sixteen support-surface
      translations, scaled to ensure responses did not involve a change in base of
      support, were then issued (backwards, forwards, left, or right). Whole-body CoM
      was estimated using four variations of a 13-segment anthropometric model: i) the
      full-model (WFM), and three simplified models, ii) excluding upper limbs (NAr);
      iii) excluding upper and lower limbs (HTP); iv) pelvis CoM (CoMp). The CoM
      calculated for each variant was then used to estimate extrapolated CoM (xCoM)
      position and the resulting MoS within the plane of postural disturbance. RESULTS:
      Comparisons of simplified models to the full model revealed significant
      differences (p < 0.05) in MoS for all models in each perturbation condition;
      however, the largest differences were following sagittal plane based
      perturbations. Poor estimates of WFM MoS were most evident for HTP and CoMp
      models; these were associated with the greatest values of RMS/maximum error,
      poorest correlations, etc. The simplified models provided low-error approximates
      for frontal plane perturbations. SIGNIFICANCE: Findings suggest that simplified
      calculations of CoM can be used by researchers without reducing MoS measurement
      accuracy; however, the degree of simplification should be context-dependent. For
      example, CoMp models may be appropriate for questions pertaining to frontal plane
      MoS; sagittal plane MoS necessitates inclusion of lower limb and HTP segments to
      prevent underestimation of postural stability.

PMID- 29653406
TI  - Introducing the risk aggregation problem to aquifers exposed to impacts of
      anthropogenic and geogenic origins on a modular basis using 'risk cells'.
AB  - Proof-of-concept is presented in this paper to a methodology formulated for
      indexing risks to groundwater aquifers exposed to impacts of diffuse
      contaminations from anthropogenic and geogenic origins. The methodology is for
      mapping/indexing, which refers to relative values but not their absolute values.
      The innovations include: (i) making use of the Origins-Source-Pathways-Receptors
      Consequences (OSPRC) framework; and (ii) dividing a study area into modular Risk
      (OSPRC) Cells to capture their idiosyncrasies with different origins. Field
      measurements are often sparse and comprise pollutants and water table, which are
      often costly; whereas supplementary data are general-purpose data, which are
      widely available. Risk mapping for each OSPRC cell is processed by dividing a
      study area into pixels and for each pixel, the risk from both anthropogenic and
      geogenic origins are indexed by using algorithms related to: (i) Vulnerability
      Indices (VI), which identify the potential for risk exposures at each pixel; and
      (ii) velocity gradient, which expresses the potency to risk exposures across the
      risk cell. The paper uses DRASTIC for anthropogenic VI but introduces a new
      framework for geogenic VI. The methodology has a generic architecture and is
      flexible to modularise risks involving any idiosyncrasies in a generic way in any
      site exposed to environmental pollution risks. Its application to a real study
      area provides evidence for the proof-of-concept for the methodology by a set of
      results that are fit-for-purpose and provides an insight into the study area
      together with the identification of its hotspots.

PMID- 29653407
TI  - A new Alzheimer's disease cell model using B cells to induce beta amyloid plaque
      formation and increase TNF alpha expression.
AB  - Different cell models have been developed for the study of Alzheimer's disease
      (AD) pathways. The neuronal dysfunction and cell death mechanisms that are
      commonly found in this disease are due to the production of high levels of
      cytokines and the formation of amyloid plaques. In the cell model introduced in
      the present study, the production of these two important factors is induced by
      using B cells from an AD patient. The B cells of an Alzheimer's patient and a
      normal control were immortalized by using EBV (Epstein-Barr virus) to produce a
      lymphoblastoid cell line (LCL). The amount of TNF alpha cytokine was evaluated at
      the RNA and protein levels by RT-PCR and ELISA, respectively. The AD LCL was
      cultured with SKNMC cells with and without treatment of TNF alpha siRNA. Amyloid
      plaque formation was monitored by Congo-red staining and microscopy. The amount
      of TNF alpha cytokine was significantly increased in the AD LCL compared to the
      normal LCL. The AD LCL induced the formation of amyloid plaques in SKNMC cells.
      The AD LCL treated with TNF alpha siRNA and co-cultured with SKNMC cells
      decreased the size and number of amyloid plaques in SKNMC cells. This cellular
      model is an appropriate model for studying Alzheimer's disease and the mechanisms
      related to it, as well as for research on cytokine inhibitors, especially TNF
      alpha inhibitors.

PMID- 29653408
TI  - A new flavonoid from Stellera chamaejasme L., stechamone, alleviated 2,4
      dinitrochlorobenzene-induced atopic dermatitis-like skin lesions in a murine
      model.
AB  - Stellera chamaejasme L. (family Thymelaeaceae), also known as 'Langdu', has been
      traditionally used to treat of skin-related diseases, such as, psoriasis and skin
      ulcers. The aim of this study was to identify the biologically active component
      of S. chamaejasme and evaluate its preventive effects on IL-4 and mast cell
      degranulation in RBL-2H3 cells and on the development of atopic dermatitis (AD)
      in 2,4-dinitrochlorobenzene (DNCB)-treated SKH-1 hairless mice. A novel
      flavonoid, genkwanin 5-O-xylosyl(1 -> 2)glucoside (named stechamone), and three
      known compounds (umbelliferone, luteolin, and luteolin-7-O-glucoside) were
      isolated from the aerial parts of S. chamaejasme using chromatographic methods.
      Of these four compounds, stechamone most potently inhibited IL-4 production and
      mast cell degranulation in RBL-2H3 cells. Topical application of 0.5% stechamone
      improved atopic skin symptoms, including, erythema (redness), pruritus (itching),
      exudation (weeping), excoriation (peeling), and lichenification (skin thickening)
      in DNCB-treated AD mice by accelerating skin barrier recovery function and
      suppressing inflammatory cell infiltration. In addition, stechamone attenuated
      DNCB-induced increases in IL-4 (an inflammatory TH2 cytokine) expression and in
      serum IgE levels in our murine model of AD. DNCB induced AD-like skin lesions,
      but treatment with stechamone exhibited strong anti-atopic activity by regulating
      skin barrier function and reducing inflammatory responses. The results obtained
      suggest stechamone is a potential anti-atopic agent and treatment for skin
      inflammatory diseases.

PMID- 29653409
TI  - Relationship between blood parameters and Clonorchis sinensis infection: A
      retrospective single center study.
AB  - Our study aims to retrospectively investigate neutrophil-to-lymphocyte ratio
      (NLR), platelet-to-lymphocyte ratio (PLR) and eosinophil-to-lymphocyte ratio
      (ELR) in patients infected with Clonorchis sinensis. This study analyzes a total
      of 151 patients with C. sinensis infections and 53 healthy control patients from
      our hospital. We found close relationships between the three candidate markers
      and the stages of C. sinensis infection-related biliary obstruction. The NLRs,
      PLRs and ELRs of patients with C. sinensis infections were significantly higher
      than those of healthy individuals; of those, ELRs showed the most superior
      diagnostic accuracy (sensitivity = 62.9%, specificity = 92.5%). Further, we
      constituted a logistic regression prediction model; applying two variables (age
      and NLR) with a sensitivity of 88.89% and a specificity of 83.78% in
      differentiating C. sinensis-related cholelithiasis from C. sinensis-untreated
      patients. Cancer antigen 19-9 (CA19-9) is a commonly used marker in the diagnosis
      of cholangiocarcinoma. Significant correlation was observed between NLR and CA19
      9 in patients with C. sinensis-related cholangiocarcinoma (r = 0.590, P = 0.000).
      In the receiver operating characteristic analysis for separating C. sinensis
      related cholelithiasis and cholangiocarcinoma, the cutoff value of PLR was 145.14
      with a sensitivity of 65.62% and a specificity of 68.89%; the sensitivity of CA19
      9 was 75.00% with a specificity of 77.78%. PLR showed acceptable efficiency to
      separate C. sinensis-related cholelithiasis from cholangiocarcinoma. In
      conclusion, all of the candidate markers (PLRs, NLRs and ELRs) may act as the
      valuable supplement in detecting C. sinensis infections and diseases.

PMID- 29653410
TI  - Rescue of iCIKs transfer from PD-1/PD-L1 immune inhibition in patients with
      resectable tongue squamous cell carcinoma (TSCC).
AB  - OBJECTIVES: The purpose of this study is to evaluate the therapeutic efficacy and
      the role of PD-1/PD-L1 pathway in tongue squamous cell carcinoma (TSCC) patients
      treated with radical operation combined with chemotherapy and improving cytokine
      induced killer cells (iCIKs) transfer. METHODS: Thirteen patients who received
      radical resection and chemotherapy were enrolled in this study. PD-1/PD-L1
      expression was evaluated in TSCC patients. ICIKs were cultured from patient
      derived peripheral blood mononuclear cells (PBMCs) in vitro. The immunological
      differences underlying iCIKs transfer were investigated through phenotype,
      cytokine secretion and PD-1/PD-L1 inhibition analysis. RESULTS: The serum PD-L1
      levels were elevated in the TSCC patients. PD-L1 was detected on both human TSCC
      cells and tumour tissue sections. PD-1 expression was much higher on the PBMCs of
      TSCC patients than on in vitro cultured iCIKs. Interruption of PD-1/PD-L1
      interaction enhanced the cytotoxicity of iCIKs in vitro. CD3 + CD8+ T cell
      proportion and cytokine IL-6 secretion decreased after chemotherapy. The infusion
      of iCIKs effectively reversed the immunosuppression through the upregulation of
      the CD3 + CD8+ T cell proportion and Th cell cytokine secretion (IFN-gamma, TNF
      alpha, IL-4 and IL-6). Twelve responders are currently alive (95.7+ months),
      another patient 83 months. CONCLUSION: Our findings indicated that the PD-1/PD-L1
      interaction contributes to the immunosuppression in TSCC patients. ICIKs transfer
      is an effective therapy to reverse the immunosuppression caused by surgical
      procedures and chemotherapy and improve immune system function.

PMID- 29653412
TI  - Sensorimotor gating deficits and effects of antipsychotics on the hyperactivity
      in VGF-overexpressing mice.
AB  - BACKGROUND: VGF nerve growth factor inducible (VGF) is a neuropeptide which is
      expressed in neuronal cells and endocrine cells. VGF is induced by several
      neurotrophic factors. The expression level of VGF in patients with schizophrenia
      is increased in cerebrospinal fluid (CSF) and prefrontal cortex. In our previous
      study, we generated mice in which the expression level of VGF in the brain was
      increased. VGF-overexpressing mice exhibited abnormal behaviors including
      hyperactivity. However, it remains unknown whether VGF-overexpressing mice
      exhibit the endophenotype of schizophrenia and whether abnormal behaviors in
      these mice can be improved by antipsychotics. METHODS: In the present study, we
      investigated schizophrenia-like behaviors and the responsiveness to
      antipsychotics in transgenic mice. RESULTS: VGF-overexpressing mice (1) exhibited
      prepulse inhibition (PPI) impairment, (2) showed normalized hyperactivity
      following antipsychotic drug treatment, and (3) showed abnormal responsiveness to
      haloperidol. CONCLUSION: Upregulation of VGF may be implicated in the
      pathophysiology of schizophrenia and abnormalities of dopaminergic signaling.

PMID- 29653411
TI  - Autophagy inhibition attenuates hyperoxaluria-induced renal tubular oxidative
      injury and calcium oxalate crystal depositions in the rat kidney.
AB  - Hyperoxaluria-induced oxidative injury of renal tubular epithelial cell is a
      casual and essential factor in kidney calcium oxalate (CaOx) stone formation.
      Autophagy has been shown to be critical for the regulation of oxidative stress
      induced renal tubular injury; however, little is known about its role in kidney
      CaOx stone formation. In the present study, we found that the autophagy
      antagonist chloroquine could significantly attenuate oxalate-induced autophagy
      activation, oxidative injury and mitochondrial damage of renal tubular cells in
      vitro and in vivo, as well as hyperoxaluria-induced CaOx crystals depositions in
      rat kidney, whereas the autophagy agonist rapamycin exerted contrasting effects.
      In addition, oxalate-induced p38 phosphorylation was significantly attenuated by
      chloroquine pretreatment but was markedly enhanced by rapamycin pretreatment,
      whereas the protective effect of chloroquine on rat renal tubular cell oxidative
      injury was partly reversed by a p38 protein kinase activator anisomycin.
      Furthermore, the knockdown of Beclin1 represented similar effects to chloroquine
      on oxalate-induced cell oxidative injury and p38 phosphorylation in vitro. Taken
      together, our results revealed that autophagy inhibition could attenuate oxalate
      induced oxidative injury of renal tubular cell and CaOx crystal depositions in
      the rat kidney via, at least in part, inhibiting the activation of p38 signaling
      pathway, thus representing a novel role of autophagy in the regulation of oxalate
      induced renal oxidative injury and CaOx crystal depositions for the first time.

PMID- 29653413
TI  - Influence of propafenone on the anticonvulsant activity of various novel
      antiepileptic drugs in the mouse maximal electroshock model.
AB  - BACKGROUND: The main mechanism of action of propafenone (antiarrhythmic drug)
      involves the inhibition of the fast inward sodium current during phase 0 of the
      action potential. Sodium channel-blocking activity is also characteristic for
      some antiepileptic drugs. Therefore, it could be assumed that propafenone may
      also affect seizures. In the present study, we evaluated the effect of
      propafenone on the protective effect of oxcarbazepine, lamotrigine, topiramate
      and pregabalin against the maximal electroshock-induced seizures in mice.
      METHODS: Anticonvulsant activity of propafenone was assessed with the maximal
      electroshock seizure threshold (MEST) test. Influence of propafenone on the
      anticonvulsant activity of antiepileptic drugs was estimated in the mouse maximal
      electroshock model (MES). Drug-related adverse effects were determined in the
      chimney test (motor coordination) and passive-avoidance task (long-term memory).
      Brain concentrations of antiepileptics were assessed by fluorescence polarization
      immunoassay. RESULTS: Propafenone at doses 60-90mg/kg significantly increased the
      threshold of seizures, in turn at doses 5-50mg/kg did not affect this parameter.
      Administration of propafenone at the subthreshold dose of 50mg/kg increased
      antielectroshock activity of oxcarbazepine, topiramate and pregabalin, but not
      that of lamotrigine. As regards adverse effects, propafenone alone and in
      combination with antiepileptic drugs did not significantly impair motor
      coordination or long-term memory in mice. Propafenone (50mg/kg) significantly
      increased the brain level of pregabalin. Brain concentrations of topiramate and
      oxcarbazepine were not affected. CONCLUSION: Our findings show that propafenone
      has own anticonvulsant action and enhances efficacy of oxcarbazepine, topiramate
      and pregabalin, but not that of lamotrigine, at least in experimental condition.

PMID- 29653414
TI  - New insights on the modulatory roles of metformin or alpha-lipoic acid versus
      their combination in dextran sulfate sodium-induced chronic colitis in rats.
AB  - BACKGROUND: Dextran sulfate sodium (DSS)-induced colitis is the most widely used
      model that resembles ulcerative colitis (UC) in human with challenging chronic
      mechanistic oxidative stress-inflammatory/immunological cascades. In models of
      acute colitis, reduction of oxidative stress and inflammatory burdens beside
      manipulation of many transcriptional factors were achieved by metformin or alpha
      lipoic acid (alpha-LA). Currently, in vivo DSS-induced chronic colitis was
      conducted and the possible therapeutic roles of metformin and/or alpha-LA were
      explored. METHODS: Chronic UC was induced by adding 5% DSS orally in drinking
      water for 7days followed by 3% DSS in drinking water for 14days in adult male
      albino Wistar rats. Intraperitoneal administration of alpha-LA (25mg/kg,
      twice/day) and/or metformin (100mg/kg/day) were set at day 7 of DSS
      administration and continued for 14days. Body weights, survival rates, disease
      activity index (DAI), colonic oxidative stress markers, tumor necrosis factor
      (TNF)-alpha levels, colonic nuclear factor-kappa-B (NF-kappaB)
      immunohistochemical expression, and the colonic histopathological changes were
      observed. RESULTS: Metformin or/and alpha-LA attenuated the severity of the DSS
      induced colitis through improving the reductions in body weights, the DAI, the
      colonic oxidative stress markers, TNF-alpha, and NF-kappaB levels, and the
      morphological mucosal damage scores. Significant synergetic therapeutic effects
      were observed with combined therapeutic regimens. CONCLUSION: Therapeutically,
      metformin and alpha-LA could be administered in chronic colitis. The combination
      of currently used pharmaceutics with natural and synthetic potent antioxidant
      compounds will become a therapeutic strategy of choice for UC to improve the
      quality of life if sufficient clinical trials are available.

PMID- 29653415
TI  - Carotid arteritis causing amaurosis fugax and ischaemic cerebrovascular events in
      neurosarcoidosis.
AB  - OBJECTIVE: To present and review the vascular consequences of arteritis in
      neurosarcoidosis. PATIENT AND METHODS: neurosarcoidosis is typically an
      inflammatory disorder of the meninges surrounding the brain and spinal cord.
      Although inflammation of small and medium sized vessels is seen pathologically
      and vasculitis is occasionally described, a large intracerebral arteritis has not
      previously been reported. A few case reports exist, however, which describe the
      vascular consequences of large vessel compromise in the disorder. We review the
      literature and present a new case with novel MRI features which imply carotid
      arteritis. RESULTS: The case presented with a disorder of the carotid artery on
      one side leading to a series of TIAs. Inflammation of the wall of the carotid
      artery was seen adjacent to a granulomatous leptomeningitis. The disorder
      responded to immunosuppressive therapy without recurrence. CONCLUSIONS: The
      imaging features suggest a granulomatous infiltration of the carotid artery wall
      leading to arteritis followed by disorganisation of the internal elastic lamina
      and fibrosis. The data provide further insight into the pathogenesis of
      neurological impairments in neurosarcoidosis. The MRI features of carotid
      arteritis in neurosarcoidosis have not previously been demonstrated.

PMID- 29653416
TI  - The structure of the Patient Health Questionnaire-9 in pregnant women in Spain.
AB  - OBJECTIVE: To evaluate psychometric properties and the factor structure of the
      Spanish version of the Patient Health Questionnaire (PHQ-9) in pregnant women
      received care in an urban public hospital in Spain. RESEARCH DESIGN/SETTING: In a
      cross-sectional study, the reliability and factor structure were examined.
      Exploratory and confirmatory factor analyses were conducted to examine the latent
      structure of the PHQ-9 with a pregnant Spanish-speaking sample (n = 445)
      recruited during the first trimester in an obstetrics clinic in Madrid.
      MEASUREMENTS AND FINDINGS: The Spanish version of PHQ-9 had moderate internal
      consistency (alpha = 0.81). Exploratory factor analysis revealed a two-factor
      (cognitive-affective, somatic) and three-factor (cognitive-affective, somatic,
      pregnancy-related) structure of the PHQ-9, whereas confirmatory factor analyses
      support a three-factor model (cognitive-affective, somatic, pregnancy-related) as
      the best fit to the data. KEY CONCLUSIONS: The Spanish version of PHQ-9 is
      reliable and can be used to screen for depression during pregnancy. A three
      factor model structure is adequate to evaluate the components and symptoms of
      depression for Spanish pregnant women. IMPLICATION FOR PRACTICE: Midwives can
      screen for depression during the PHQ-9 and can tailor interventions to minimize
      the adverse effects on mothers and infants, before and after birth.

PMID- 29653417
TI  - Factors associated with Chinese nulliparous women's choices of mode of delivery:
      A longitudinal study.
AB  - BACKGROUND: Caesarean section rates have risen beyond the WHO recommended level
      in many countries worldwide. An emerging epidemic in caesareans has appeared in
      China over the past two decades, mainly driven by non-medical factors. China's
      one-child policy was previously seen as a potential factor for contributing to
      women's high caesarean section rates. The Chinese government has officially
      announced a two-child policy in recent years, causing numerous families to
      reshape their fertility intentions and birth preferences. There have been few
      studies focusing on women's expected and actual delivery mode and the associated
      factors affecting their choices of mode of delivery. OBJECTIVE: To investigate
      nulliparous women's expected and actual mode of delivery, and the related factors
      associated with delivery mode in the context of China's two-child policy. DESIGN,
      SETTINGS, AND PARTICIPANTS: This longitudinal study approached 1368 pregnant
      women who attended the antenatal clinic regularly at a tertiary specialized
      women's hospital in Shanghai, China. Among the 1368 women, 1211 agreed to
      participate and were investigated at admission of this study. METHODS: Data were
      collected via questionnaires using Birth Attitude Questionnaire (BAQ), Subjective
      Norm Questionnaire (SNQ), and Childbirth Self-Efficacy Scale (CSES). Descriptive
      statistics and logistic regression analyses were used. RESULTS: Of 1211
      participants, the number of women expecting a vaginal delivery at three pregnancy
      stages accounted for 74%, 78%, and 83%, respectively. Finally 48% (520/1084)
      ended up having a caesarean delivery. Caesarean section for lack of medical
      indications accounted for 57% (297/520). Among women who met the requirements of
      two-child policy, 39% planned to have a second child. In logistic regression
      analyses, participants with stronger expectations of caesarean deliveries during
      late pregnancy (aOR, 35.18; 95% CI, 12.66-97.74), having higher scores of birth
      attitude toward CS (aOR, 1.13; 95% CI, 1.06-1.20), and with lower scores of
      intrapartum childbirth self-efficacy (aOR, 0.85; 95% CI, 0.77-0.92) had
      significantly higher odds of having an actual caesarean delivery. CONCLUSIONS:
      During the initial period of China's two-child policy, the majority of women
      value vaginal delivery whereas high caesarean section rate still becomes a great
      concern in current China. Individual preferences, birth attitude, and childbirth
      self-efficacy are altogether associated with women's different choices of mode of
      delivery.

PMID- 29653418
TI  - Simple and label-free pathogen enrichment via homobifunctional imidoesters using
      a microfluidic (SLIM) system for ultrasensitive pathogen detection in various
      clinical specimens.
AB  - Diseases caused by pathogenic microorganisms including bacteria and viruses can
      cause serious medical issues including death and result in huge economic losses.
      Despite the myriad of recent advances in the rapid and accurate detection of
      pathogens, large volume clinical samples with a low concentration of pathogens
      continue to present challenges for diagnosis and surveillance. We here report a
      simple and label-free approach via homobifunctional imidoesters (HIs) with a
      microfluidic platform (SLIM) to efficiently enrich and extract pathogens at low
      concentrations from clinical samples. The SLIM system consists of an assembled
      double microfluidic chip for streamlining large volume processing and HIs for
      capturing pathogens and isolating nucleic acids by both electrostatic and
      covalent interaction without a chaotropic detergent or bulky instruments. The
      SLIM system significantly increases the enrichment and extraction rate of
      pathogens (up to 80% at 10 CFU (colony forming unit) in a 1 mL volume within 50
      min). We demonstrated its clinical utility in large sample volumes from 46
      clinical specimens including environmental swabs, saliva, and blood plasma. The
      SLIM system showed higher sensitivity with these samples and could detect
      pathogens that were below the threshold of detection with other methods. Finally,
      by combining our SLIM approach with an isothermal optical sensor, pathogens could
      be detected at a very high sensitivity in blood plasma samples within 80 min via
      enrichment, extraction and detection steps. Our SLIM system thus provides a
      simple, reliable, cost-effective and ultrasensitive pathogen diagnosis platform
      for use with large volume clinical samples and would thus have significant
      utility for various infectious diseases.

PMID- 29653419
TI  - A sensitive signal-on photoelectrochemical sensor for tetracycline determination
      using visible-light-driven flower-like CN/BiOBr composites.
AB  - As a broad-spectrum antibiotic, tetracycline (TC) is widely used in agricultural
      purposes and human therapy. More attention is paid to TC as a serious threat to
      human health, including the fast spreading of antibiotic resistance gene and the
      serious toxicity to aquatic organisms. Therefore, the timely and accurate
      determination of TC residues is an urgent task to protect the safety of human.
      Herein, an effective and facile photoelectrochemical sensor platform based on
      carbon nitride/bismuth oxyhalide (CN/BiOBr) composites can be constructed for
      monitoring TC. The flower-like CN/BiOBr composites are prepared via a simple one
      pot ethylene glycol-assisted solvothermal process with the addition of ionic
      liquid 1-hexadecyl-3-methylimidazolium bromide ([C16mim]Br). In view of matched
      energy band positions of CN and BiOBr, the addition of CN can reduce the
      recombination of photogenerated electron-hole pairs and improve the efficiency of
      visible light utilization, leading to enhancing photoelectrochemical response of
      BiOBr. Under light excitation, the photocurrent of CN/BiOBr composites is
      drastically improved, which is 6 times as much as that of pure BiOBr. Considering
      the superior photoelectrochemical performance, a photoelectrochemical sensor for
      monitoring TC has been developed, displaying linearly enhanced photocurrent with
      increasing the TC concentration. Two linear relationships received are from 8.0
      to 4.0 * 102 ng mL-1, and 4.0 * 102 to 5.2 * 103 ng mL-1, respectively. The
      detection limit is 3.8 ng mL-1. The photoelectrochemical sensor exhibits a series
      of benefits including excellent stability, a wide linear range, a low detection
      limit and good anti-interference ability. Therefore, this work may offer great
      promises in providing a universal and efficient photoelectrochemical sensor for
      the tetracycline detection, and pave the way of constructing more materials used
      in photoelectrochemical detection field.

PMID- 29653421
TI  - Functionalizing bottom ash from biomass power plant for removing methylene blue
      from aqueous solution.
AB  - In order to seek a possible path for utilization bottom ash, the solid waste from
      biomass incineration for power generation, its basic characteristics were
      investigated, and removing methylene blue (MB) from aqueous solution was
      attempted as well. Results indicated bottom ash dominantly contained Si and Ca
      related minerals with >35 mineral elements, meanwhile, it was typically
      characterized by alkalinity (pH of 9.5) and low specific surface area (14.5m2/g).
      As the only bottom ash was employed for removing MB, removal efficiency was lower
      than 44%, however, it was greatly improved to 100% as hydrogen peroxide was
      supplemented (final concentration of 4.0%). Based on the elucidated mechanisms,
      Fenton-like reaction was triggered by bottom ash, which was dominantly
      responsible for removing MB, rather than the adsorption by bottom ash. Besides,
      increasing reaction temperature and duration dramatically promoted MB removal by
      bottom ash with the aid of hydrogen peroxide (HBA). A great promotion on MB
      removal from 92.3mg/g to 143.9mg/g was achieved as pH was adjusted from 2.0 to
      5.0, indicating MB removal was pH-dependent. The maximum removal of 260.9mg/g was
      achieved by HBA at a relatively high initial MB concentration of 2000.0mg/L,
      suggesting a great potential in treating dye wastewater by functionalizing bottom
      ash with the aid of hydrogen peroxide. Moreover, the released heavy metals and
      derived by-products from MB removal were acceptable in consideration of their
      potential environmental risks. Thus, the current work offers a new path to
      valorize the solid waste in biomass electricity generation plant.

PMID- 29653420
TI  - One-by-one imprinting in two eccentric layers of hollow core-shells: Sequential
      electroanalysis of anti-HIV drugs.
AB  - Double layered one-by-one imprinted hollow core-shells@ pencil graphite electrode
      was fabricated for sequential sensing of anti-HIV drugs. For this, two eccentric
      layers were developed on the surface of vinylated silica nanospheres to obtain
      double layered one-by-one imprinted solid core-shells. This yielded hollow core
      shells on treatment with hydrofluoric acid. The modified hollow core-shells
      (single layered dual imprinted) evolved competitive diffusion of probe/analyte
      molecules. However, the corresponding double layered one-by-one imprinted hollow
      core-shells (outer layer imprinted with Zidovudine, and inner layer with
      Lamivudine) were found relatively better owing to their bilateral diffusions into
      molecular cavities, without any competition. The entire work is based on
      differential pulse anodic stripping voltammetry at double layered one-by-one
      imprinted hollow core-shells. This resulted in indirect detection of electro
      inactive targets with limits of detection as low as 0.91 and 0.12 (aqueous
      sample), 0.94 and 0.13 (blood serum), and 0.99 and 0.20 ng mL-1 (pharmaceutics)
      for lamivudine and zidovudine, respectively in anti-HIV drug combination.

PMID- 29653422
TI  - High-throughput sequencing reveals microbial communities in drinking water
      treatment sludge from six geographically distributed plants, including
      potentially toxic cyanobacteria and pathogens.
AB  - The microbial community structures of drinking water treatment sludge (DWTS)
      generated for raw water (RW) from different locations and with different source
      types - including river water, lake water and reservoir water -were investigated
      using high-throughput sequencing. Because the unit operations in the six DWTPs
      were similar, community composition in fresh sludge may be determined by
      microbial community in the corresponding RW. Although Proteobacteria,
      Cyanobacteria, Bacteroidetes, Firmicutes, Verrucomicrobia, and Planctomycetes
      were the dominant phyla among the six DWTS samples, no single phylum exhibited
      similar abundance across all the samples, owing to differences in total
      phosphorus, chemical oxygen demand, Al, Fe, and chloride in RW. Three genera of
      potentially toxic cyanobacteria (Planktothrix, Microcystis and
      Cylindrospermopsis), and four potential pathogens (Escherichia coli, Bacteroides
      ovatus, Prevotella copri and Rickettsia) were found in sludge samples. Because
      proliferation of potentially toxic cyanobacteria and Rickettsia in RW was mainly
      affected by nutrients, while growth of Escherichia coli, Bacteroides ovatus and
      Prevotella copri in RW may be influenced by Fe, control of nutrients and Fe in RW
      is essential to decrease toxic cyanobacteria and pathogens in DWTS.

PMID- 29653423
TI  - Combined effects of physical environmental conditions and anthropogenic
      alterations are associated with macrophyte habitat fragmentation in rivers -
      Study of the Danube in Serbia.
AB  - We hypothesize that the physical features of river habitats and anthropogenic
      hydromorphological alterations influence macrophyte communities and lead to
      habitat fragmentation. Sampling included 1081 contiguous survey units positioned
      in the main channel and side arms along 588km of the Danube River, along its
      middle course. To identify habitat fragments, Multivariate Regression Tree
      analysis (MRT) was applied on macrophyte and environmental data. Indicator
      species analyses were combined with MRT. To identify habitat fragments on a scale
      larger than final MRT groups, we set thresholds for an MRT complexity parameter.
      We identified 20 fine, 7 medium, and 3 large scale habitat fragments. Damming was
      the main fragmentation agent. Macrophyte communities show continuous variation at
      all scales of habitat fragmentation. High species diversity indicates major
      anthropogenic alteration of the river's hydrology and decline of the natural
      riparian zone. Future studies of the macrophyte communities, and their habitat
      fragmentation must include more factors (e.g. nutrient status, physicochemical
      quality of the water, etc.), as well as assessment of the importance of
      tributaries.

PMID- 29653424
TI  - Methane in groundwater from a leaking gas well, Piceance Basin, Colorado, USA.
AB  - Site-specific and regional analysis of time-series hydrologic and geochemical
      data collected from 15 monitoring wells in the Piceance Basin indicated that a
      leaking gas well contaminated shallow groundwater with thermogenic methane. The
      gas well was drilled in 1956 and plugged and abandoned in 1990. Chemical and
      isotopic data showed the thermogenic methane was not from mixing of gas-rich
      formation water with shallow groundwater or natural migration of a free-gas
      phase. Water-level and methane-isotopic data, and video logs from a deep
      monitoring well, indicated that a shale confining layer ~125m below the zone of
      contamination was an effective barrier to upward migration of water and gas. The
      gas well, located 27m from the contaminated monitoring well, had ~1000m of
      uncemented annular space behind production casing that was the likely pathway
      through which deep gas migrated into the shallow aquifer. Measurements of soil
      gas near the gas well showed no evidence of methane emissions from the soil to
      the atmosphere even though methane concentrations in shallow groundwater (16 to
      20mg/L) were above air-saturation levels. Methane degassing from the water table
      was likely oxidized in the relatively thick unsaturated zone (~18m), thus
      rendering the leak undetectable at land surface. Drilling and plugging records
      for oil and gas wells in Colorado and proxies for depth to groundwater indicated
      thousands of oil and gas wells were drilled and plugged in the same timeframe as
      the implicated gas well, and the majority of those wells were in areas with
      relatively large depths to groundwater. This study represents one of the few
      detailed subsurface investigations of methane leakage from a plugged and
      abandoned gas well. As such, it could provide a useful template for prioritizing
      and assessing potentially leaking wells, particularly in cases where the leakage
      does not manifest itself at land surface.

PMID- 29653425
TI  - Microplastics and polycyclic aromatic hydrocarbons (PAHs) in Xiamen coastal
      areas: Implications for anthropogenic impacts.
AB  - Microplastics and polycyclic aromatic hydrocarbons (PAHs) were investigated to
      study the influence of human activities and to find their possible relationship
      on the coastal environments, where the coastal areas around Xiamen are undergoing
      intensive processes of industrialization and urbanization in the southeast China.
      The abundance of microplastics in Xiamen coastal areas was 103 to
      2017particles/m3 in surface seawater and 76 to 333 particles/kg in sediments.
      Concentrations of dissolved PAHs varied from 18.1 to 248ng/L in surface seawater.
      The abundances of microplastics from the Western Harbor in surface seawater and
      sediments were higher than those from other areas. Foams were dominated in
      surface seawater samples, however, no foams were found in sediments samples. The
      microscope selection and FTIR analysis suggested that polyethylene (PE) and
      polypropylene (PP) were dominant microplastics. The cluster analysis results
      demonstrated that fibers and granules had the similar sources, and films had
      considerably correlation with all types of PAHs (3 or 4-ring PAHs and alkylated
      PAHs). Plastic film mulch from agriculture practice might be a potential source
      of microplastics in study areas. Results of our study support that river runoff,
      watershed area, population and urbanization rate influence the distribution of
      microplastics in estuarine surface water, and the prevalence of microplastic
      pollution calls for monitoring microplastics at a national scale.

PMID- 29653426
TI  - Evaluation of maximum potential gene flow from herbicide resistant Brassica napus
      to its male sterile relatives under open and wind pollination conditions.
AB  - Pollen-mediated gene flow (PMGF) from genetically modified (GM) Brassica napus to
      its wild relatives by wind and insects is a major ecological concern in
      agricultural ecosystems. This study conducted is to estimate maximum potential
      gene flow and differentiate between wind- and bee-mediated gene flows from
      herbicide resistant (HR) B. napus to its closely-related male sterile (MS)
      relatives, B. napus, B. juncea and Raphanus sativus. Various markers, including
      pods formation in MS plants, herbicide resistance, and SSR markers, were used to
      identify the hybrids. Our results revealed the following: 1) maximum potential
      gene flow (a maximum % of the progeny of pollen recipient confirmed hybrid) to MS
      B. napus ranged from 32.48 to 0.30% and from 14.69 to 0.26% at 2-128 m from HR B.
      napus under open and wind pollination conditions, respectively, and to MS B.
      juncea ranged from 21.95 to 0.24% and from 6.16 to 0.16%, respectively; 2)
      estimates of honeybee-mediated gene flow decreased with increasing distance from
      HR B. napus and ranged from 17.78 to 0.03% at 2-128 m for MS B. napus and from
      15.33 to 0.08% for MS B. juncea; 3) a small-scale donor plots would strongly
      favour insect over wind pollination; 4) no gene flow occurred from HR B. napus to
      MS R. sativus. Our approach and findings are helpful in understanding the
      relative contribution of wind and bees to gene flow and useful for estimating
      maximum potential gene flow and managing environmental risks associated with gene
      flow.

PMID- 29653427
TI  - Potential of Portuguese vine shoot wastes as natural resources of bioactive
      compounds.
AB  - Since annually a high amount of wastes is produced in vine pruning, the aim of
      this study was to evaluate the potential of vine shoots from two Portuguese grape
      varieties (Touriga Nacional - TN and Tinta Roriz - TR) to be used as a natural
      source of phenolic compounds. To reach this goal, three techniques were explored,
      namely microwave-assisted extraction (MAE), subcritical water extraction (SWE)
      and conventional extraction (CE). The phenolic composition of the extracts,
      antioxidant and biological activities were evaluated by spectrophotometry and
      chromatography. MAE and SWE produced the highest concentrated extracts. TR vine
      shoot variety had the highest antioxidant activity and total phenolic (32.1+/
      0.9mggallicacidequivalents/g dry sample), as well as flavonoid content (18.7+/
      1.2mgepicatechinequivalents/g dry sample). For the first time, the biological
      activity of the vine shoot extracts was tested. Results demonstrated that all of
      them had antimicrobial potential against different bacteria and yeasts, and the
      ability of inhibiting alpha-amylase and acetylcholinesterase enzymes, with MAE TR
      extracts being the most efficient. HPLC analysis enabled the identification of
      different phenolic compounds, with gallic acid, catechin, myricetin and
      kaempferol-3-O-rutinoside being the main contributors to the phenolic
      composition. Portuguese vine shoot wastes could serve as easily accessible source
      of natural antioxidants for the food or pharmaceutical industries.

PMID- 29653428
TI  - The threshold of influent ammonium concentration for nitrate over-accumulation in
      a one-stage deammonification system with granular sludge without aeration.
AB  - Low-strength ammonium is still a challenge for the mainstream deammonification
      because of nitrate over-accumulation. In this study, the threshold of influent
      ammonium concentration of one-stage deammonification system with granular sludge
      was investigated, by stepwise decreasing influent ammonium from high
      concentrations (280mg/L to 140mg/L) to the low concentration (70mg/L) in 108d at
      32 degrees C without aeration. Results showed that, under 70mg/L NH4+-N, DeltaNO3
      -N/DeltaNH4+-N ratio increased to 0.2, deviated from the theoretical value of
      0.11, with ammonium and TN removal efficiencies of 91% and 71%, respectively.
      However, under both high ammonium concentrations (280mg/L and 140mg/L), nitrate
      production stabilized at only 13%. Chloroflexi, Planctomycetes and Proteobacteria
      contributed >70% of the communities under all three ammonium concentrations. As
      influent ammonium decreasing, the relative abundances of bacteria for anammox,
      aerobic oxidizing and denitrifying decreased, while NOB (nitrite oxidizing
      bacteria) abundance increased greatly. So 70mg/L was the threshold of influent
      ammonium concentration for stable deammonification without organic influent. It
      was the decrease of functional bacteria and overgrowth of NOB that worsen the
      deammonification performance under low-strength ammonium.

PMID- 29653429
TI  - GIS-based groundwater potential analysis using novel ensemble weights-of-evidence
      with logistic regression and functional tree models.
AB  - The aim of the current study was to produce groundwater spring potential maps
      using novel ensemble weights-of-evidence (WoE) with logistic regression (LR) and
      functional tree (FT) models. First, a total of 66 springs were identified by
      field surveys, out of which 70% of the spring locations were used for training
      the models and 30% of the spring locations were employed for the validation
      process. Second, a total of 14 affecting factors including aspect, altitude,
      slope, plan curvature, profile curvature, stream power index (SPI), topographic
      wetness index (TWI), sediment transport index (STI), lithology, normalized
      difference vegetation index (NDVI), land use, soil, distance to roads, and
      distance to streams was used to analyze the spatial relationship between these
      affecting factors and spring occurrences. Multicollinearity analysis and feature
      selection of the correlation attribute evaluation (CAE) method were employed to
      optimize the affecting factors. Subsequently, the novel ensembles of the WoE, LR,
      and FT models were constructed using the training dataset. Finally, the receiver
      operating characteristic (ROC) curves, standard error, confidence interval (CI)
      at 95%, and significance level P were employed to validate and compare the
      performance of three models. Overall, all three models performed well for
      groundwater spring potential evaluation. The prediction capability of the FT
      model, with the highest AUC values, the smallest standard errors, the narrowest
      CIs, and the smallest P values for the training and validation datasets, is
      better compared to those of other models. The groundwater spring potential maps
      can be adopted for the management of water resources and land use by planners and
      engineers.

PMID- 29653430
TI  - Photo-oxygenation for nitritation and the effect of dissolved oxygen
      concentrations on anaerobic ammonium oxidation.
AB  - Removal of nitrogen from wastewater without using electricity consuming aerators
      was previously observed in photo-bioreactors with a mixed algal-bacterial
      biomass. Algammox is the particular process based on algae, ammonium oxidizing
      organisms and anammox bacteria. In this research the activity of anammox bacteria
      in such an oxygen-producing environment was tested, as well as the effect of
      short-duration increase in dissolved oxygen (DO) to values potentially inhibiting
      anammox activity. Sequencing batch photo-bioreactors were fed with settled
      domestic wastewater enriched with ammonium (200mgNH4+-N/L) and exposed to light
      within the photosynthetic active range with intensity of about 500MUmol/m2.s.
      Each cycle consisted of 12h illumination and 12h darkness. A well-settling
      biomass (10days solids retention time) developed that carried out nitritation,
      nitrification and anammox. Ammonium removal rate during the light period was
      4.5mgN-NH4+/L.h, equal to 858mgN-NH4+/m2.h or 477mgN-NH4+/(mol photons). When the
      reactors were aerated for 3h to temporarily increase the DO, anammox was
      inhibited at bulk DO values larger than 0.4-1.0mg/L. For almost oxygen saturated
      conditions, recovery time was about 9days. Algammox photo-bioreactors are
      therefore able to overcome short periods of oxygen stress, provided they occur
      only occasionally.

PMID- 29653431
TI  - Inhibition of NAMPT sensitizes MOLT4 leukemia cells for etoposide treatment
      through the SIRT2-p53 pathway.
AB  - NAMPT (Nicotinamide phosphoribosyltransferase) catalyses the rate-limiting step
      in the NAD biosynthesis from nicotinamide and thereby regulates the activity of
      NAD-dependent enzymes. Cancer cells are highly dependent on NAD for energy and
      DNA repair processes and are assumed to be more susceptible to an inhibition of
      NAD synthesis than non-transformed cells. We aimed to investigate whether or not
      inhibition of NAMPT with its specific inhibitor FK866 can sensitize leukemia
      cells for chemotherapeutic agents. NAMPT protein abundance, enzymatic activity
      and NAD concentrations were significantly higher in Jurkat and Molt-4 leukemia
      cell lines compared to normal peripheral blood mononuclear cells. Combination of
      etoposide and FK866 caused increased cell death in leukemia cell lines compared
      to etoposide alone. Etoposide decreased protein abundance of NAD-dependent
      deacetylases SIRTUIN1. After combining etoposide and FK866 treatment SIRTUIN2 was
      further decreased and accumulation and acetylation of the downstream target p53
      was further enhanced in MOLT4 cells. Concomitantly, protein abundance of p21 and
      cleaved BAX was increased. Targeting NAMPT could be a novel therapeutic strategy
      to enhance the efficacy of chemotherapeutic agents such as etoposide against
      leukemia.

PMID- 29653432
TI  - In-vitro evaluation and in-silico studies applied on newly synthesized amide
      derivatives of N-phthaloylglycine as Butyrylcholinesterase (BChE) inhibitors.
AB  - Amide derivatives of N-phthaloylglycine were synthesized under Schotten Baumann
      reaction condition. The structures of synthesized compounds (4a-d) were
      characterized by using FTIR, 1HNMR and EI-MS. The compounds were evaluated for
      their in-vitro Butyrylcholinesterase inhibition and all of them exhibited good
      activity against this enzyme. Compound 4a (IC50 = 6.5 +/- 0.1) was found to be
      most potent compared with the reference compound Galantamine (IC50 = 6.6 +/-
      0.00038) and the other compounds (4b,4c,4d) were also possess that activity and
      hence can be employed for the discovery of lead compounds against Alzheimer's
      disease. The depth analysis of the binding mechanism of these newly synthesized
      compounds inside the binding gorge of BChE, an in silico technique, molecular
      docking was performed. All the compounds were found to be well accommodated
      within the binding pocket of BChE. Compounds 4a, 4b and 4c showed hydrogen
      bonding interaction with binding site residue TYR332. Moreover, hydrophobic and
      pi-pi interaction assisted the compounds to attain their enzyme inhibitory
      activity. These theoretical studies showed significant correlation with
      experimental results.

PMID- 29653433
TI  - Mindfulness as a mediator of the association between adverse childhood
      experiences and alcohol use and consequences.
AB  - One-third of college students report past-year heavy episodic drinking, making
      college student alcohol use an important area for continued research. Research
      has consistently linked early experiences of adversity to problematic substance
      use in adolescence and adulthood. Given the negative health consequences
      associated with heavy episodic drinking, it is imperative to identify mechanisms
      that contribute to this relation. Low levels of mindfulness have been linked to
      early adversity as well as impulsivity and alcohol use, therefore, the current
      study aims to examine the mediating role of mindfulness in the relation between
      early adversity and current alcohol use and consequences. Undergraduate students
      (N = 385) at a Midwestern university completed an online questionnaire assessing
      experiences of childhood adversity, trait mindfulness, and current alcohol use
      and related consequences. Results indicated that increased adverse experiences
      and lower levels of mindfulness predicted both increased alcohol consumption and
      consequences (ps < 0.025), with mindfulness mediating the relationships.
      Mindfulness is a predictor of alcohol outcomes and appears to mediate the
      relation between early adversity and alcohol use and consequences. Findings
      suggest that students with a history of adversity are more likely to exhibit
      lower levels of mindfulness, which may lead to an increase in alcohol consumption
      and consequences in early adulthood. Targeted alcohol intervention efforts that
      incorporate mindfulness skills may be particularly beneficial for those who have
      experienced early adversity.

PMID- 29653434
TI  - Elevated CO2 induces alteration in lignin accumulation in celery (Apium
      graveolens L.).
AB  - Carbon dioxide (CO2) is an important regulator of plant growth and development,
      and its proportion in the atmosphere continues to rise now. Lignin is one of the
      major secondary products in plants with vital biological functions. However, the
      relationship between CO2 level and xylogenesis in celery is still unknown. In
      order to investigate the effects of increasing CO2 concentration on lignin
      accumulation in celery, 'Jinnanshiqin' were exposed to two CO2 applications, 400
      (e0) and 1000 MUmol mol-1 (e1), respectively. Plant morphology and lignin
      distribution in celery plants treated with elevated CO2 did not change
      significantly. There was an upward trend on lignin content in celery leaves, and
      the transcript abundance of 12 genes involved in lignin metabolism has altered in
      response to elevated CO2. The effects of high level of CO2 on different tissues
      were different. Our works confirmed that CO2 may play an important role in lignin
      accumulation in celery leaves. The current study will offer new evidence to
      understand the regulation mechanism of lignin biosynthesis under elevated CO2 and
      provide a reference to improve celery quality by adjusting the growth
      environment.

PMID- 29653435
TI  - Functional characterization of the gene promoter for an Elaeis guineensis
      phosphate starvation-inducible, high affinity phosphate transporter in both
      homologous and heterologous model systems.
AB  - Oil palm is grown in tropical soils with low bioavailability of Pi. A cDNA clone
      specifically expressed under phosphate-starvation condition in oil palm roots was
      identified as a high-affinity phosphate transporter (EgPHT1). The deduced amino
      acid sequence has 6 transmembrane domains each at the N- and C-termini separated
      by a hydrophilic linker. Comparison of promoter motifs within 1500 bp upstream of
      ATG of 10 promoters from high- and low-affinity phosphate transporter from both
      dicots and monocots including EgPHT1 was performed. The EgPHT1 promoter was fused
      to beta-glucuronidase (GUS) reporter gene and its activity was analysed by
      histochemical and fluorometric GUS assays in transiently transformed oil palm
      tissues and T3 homozygous transgenic Arabidopsis plants. In response to Pi
      starvation, no GUS activity was detected in oil palm leaves, but a strong
      inducible activity was observed in the roots (1.4 times higher than the CaMV35S
      promoter). GUS was specifically expressed in transgenic Arabidopsis roots under
      Pi deficiency and starvation of the other macronutrients (N and K) did not induce
      GUS activity. Eight motifs including ABRERATCAL (abscisic-acid responsive),
      RHERPATEXPA7 (root hair-specific), SURECOREATSULTR11 (sulfur-deficiency
      response), LTRECOREATCOR15 (temperature-stress response), MYB2CONSENSUSAT and
      ACGTATERD1 (water-stress response) as well as two novel motifs, 3 (TAAAAAAA) and
      26 (TTTTATGT) identified through pattern discovery, occur at significantly higher
      frequency (p < 0.05) in the high-than the low-affinity phosphate transporter
      promoters. The Pi deficiency-responsive elements in EgPHT1 includes the P1BS, W
      box, E-box and the G-box. Thus, EgPHT1 is important for improving Pi uptake in
      oil palm with potential for engineering efficient Pi acquisition.

PMID- 29653436
TI  - A chloroplast-targeted cabbage DEAD-box RNA helicase BrRH22 confers abiotic
      stress tolerance to transgenic Arabidopsis plants by affecting translation of
      chloroplast transcripts.
AB  - Although the roles of many DEAD-box RNA helicases (RHs) have been determined in
      the nucleus as well as in cytoplasm during stress responses, the importance of
      chloroplast-targeted DEAD-box RHs in stress response remains largely unknown. In
      this study, we determined the function of BrRH22, a chloroplast-targeted DEAD-box
      RH in cabbage (Brassica rapa), in abiotic stress responses. The expression of
      BrRH22 was markedly increased by drought, heat, salt, or cold stress and by ABA
      treatment, but was largely decreased by UV stress. Expression of BrRH22 in
      Arabidopsis enhanced germination and plantlet growth under high salinity or
      drought stress. BrRH22-expressing plants displayed a higher cotyledon greening
      and better plantlet growth upon ABA treatment due to decreases in the levels of
      ABI3, ABI4, and ABI5. Further, BrRH22 affected translation of several chloroplast
      transcripts under stress. Notably, BrRH22 had RNA chaperone function. These
      results altogether suggest that chloroplast-transported BrRH22 contributes
      positively to the response of transgenic Arabidopsis to abiotic stress by
      affecting translation of chloroplast genes via its RNA chaperone activity.

PMID- 29653438
TI  - The effect of a cricket fielding session on glenohumeral range of motion and
      active joint position sense.
AB  - OBJECTIVE: To assess the effects of a cricket fielding session, at an identified
      throwing injury risk workload, on shoulder joint position sense (JPS) and active
      range of motion (AROM) in cricketers. DESIGN: Repeated measures observational
      study. SETTING: Indoor cricket centre. PARTICIPANTS: Nineteen, asymptomatic
      University cricketers. MAIN OUTCOME: AROM was assessed supine at 90 degrees 
      abduction and from this 10% off end range IR and ER was used as the position
      matching angle to assess JPS. JPS error scores as well as AROM were assessed pre
      and post a cricket fielding session consisting of 40 throws. RESULTS: Following
      the cricket fielding session, no alteration in JPS in ER (p = 0.91) or IR (p =
      0.27) was observed. There was however a significant decrease in IR (-3.9 degrees
      ) following the fielding drill (p = 0.007) while no significant change was
      observed in ER or total motion. CONCLUSION: Active IR ROM is significantly
      decreased immediately following a cricket fielding drill, while no alterations in
      JPS were observed. High levels of eccentric stress have been reported in the
      external rotators after throwing which may contribute to the acute
      musculotendinous adaptations observed. Changes in IR may be a contributing factor
      to workload-acquired shoulder throwing injuries.

PMID- 29653437
TI  - Early infectious exposures are not associated with increased risk of pediatric
      onset multiple sclerosis.
AB  - OBJECTIVE: We sought to determine if early infectious exposures such as daycare,
      early use of antibiotics, vaccinations and other germ exposures including
      pacifier use and playing on grass are associated with multiple sclerosis (MS)
      risk in children. METHODS: This was a case-control study of children with MS or
      clinically isolated syndrome (CIS) and healthy controls enrolled at sixteen
      clinics participating in the US Network of Pediatric MS Centers. Parents
      completed a comprehensive environmental questionnaire that captured early
      infectious exposures, habits, and illnesses in the first five years of life. A
      panel of at least two pediatric MS specialists confirmed diagnosis of
      participants. Association of early infectious variables with diagnosis was
      assessed via multivariable logistic regression analyses, adjusting for age, sex,
      race, ethnicity, US birth region, and socioeconomic status (SES). RESULTS:
      Questionnaire responses for 326 eligible cases (mean age 14.9, 63.5% girls) and
      506 healthy pediatric subjects (mean age 14.4, 56.9% girls) were included in
      analyses. History of flu with high fever before age five (p = 0.01), playing
      outside in grass and use of special products to treat head lice or scabies (p =
      0.04) were associated with increased risk of MS in unadjusted analyses. In the
      multivariable model adjusted for age, sex, race, ethnicity, and mother's highest
      educational attainment, these results were not statistically significant.
      Notably, antibiotic use (p = 0.22) and regular daycare attendance before age 6 (p
      = 0.09) were not associated with odds of developing MS. CONCLUSION: Early
      infectious factors investigated in this study were not associated with MS risk.

PMID- 29653439
TI  - Medical cannabis: An oxymoron? Physicians' perceptions of medical cannabis.
AB  - BACKGROUND: Medical cannabis policies are changing in many places around the
      world, and physicians play a major role in the implementation of these policies.
      The aim of this study was to gain a deeper understanding of physicians' views on
      medical cannabis and its possible integration into their clinic, as well as to
      identify potential underlying factors that influence these perceptions. METHODS:
      Qualitative narrative analysis of in-depth interviews with twenty-four Israeli
      physicians from three specialties (pain medicine, oncology and family medicine).
      FINDINGS: Physicians disclosed contrasting narratives of cannabis, presenting it
      as both a medicine and a non-medicine. These divergent positions co-existed and
      were intertwined in physicians' accounts. When presenting cannabis as a non
      medicine, physicians drew on conventional medicine and prohibition as narrative
      environments. They emphasized the incongruence of cannabis with standards of
      biomedicine and presented cannabis as an addictive drug of abuse. In contrast,
      physicians drew upon unconventional medicine and palliative care as narrative
      environments while presenting cannabis as a medicine. In this narrative,
      physicians emphasized positive hands-on experiences with cannabis, and pointed to
      the limits of conventional medicine. CONCLUSION: Physicians did not have a
      consolidated perspective as to whether cannabis is a medicine or not, but rather
      struggled with this question. The dualistic narratives of cannabis reflect the
      lack of a dominant narrative environment that supports the integration of
      cannabis into medical practice. This may in turn indicate barriers to the
      implementation of medical cannabis policies. An awareness of physicians' views
      and the different levels of their willingness to implement medical cannabis
      policies is essential for policy developments in this evolving field.

PMID- 29653440
TI  - Long-Term Outcome after Dynamic Graciloplasty for Treatment of Persistent Fecal
      Incontinence in Patients with Anorectal Malformations.
AB  - PURPOSE:  Dynamic graciloplasty (DGP) has been used to treat severe fecal
      incontinence since the 1980s. Previous studies have shown an inferior outcome in
      patients with anorectal malformations (ARMs). Our experience has been that DGP
      has been appreciated by ARM -patients. The objective of the study was to evaluate
      the long-term outcome of DGP in our patients with ARM compared with patients with
      other underlying conditions. MATERIALS AND METHODS:  Twenty-three patients
      operated with DGP at our institution from 1996 to 2010 were sent validated bowel
      function and quality of life questionnaires. Eighteen of 23 responded. Seven had
      ARM and 11 had other etiologies of fecal incontinence. The mean follow-up time
      was 11.6 years (range, 5-17). RESULTS:  Four of 7 of the patients with ARM and 8
      of 11 of patients with other etiologies used their implants at follow-up. The
      Miller incontinence score was slightly higher for patients with ARMs, but they
      had less constipation and higher Fecal Incontinence Quality of Life (FIQL)- and
      36-Item Short Form Health Survey (SF-36) scores. None of the differences were
      statistically significant. CONCLUSION:  This study cannot confirm earlier reports
      in which DGP has an inferior outcome in patients with ARM. We therefore believe
      that the procedure should remain a treatment option for selected patients.

PMID- 29653441
TI  - The Impact of Groin Surgery during Childhood on the Incidence of Inguinal Hernia
      Repair and Its Postoperative Complications in Adult Life.
AB  - BACKGROUND:  Pediatric inguinal hernia, hydrocele, and cryptorchidism are common
      congenital anomalies affecting children, and require surgical intervention in
      some cases. The association between surgical treatment of these conditions and
      acquired inguinal hernia later in life is poorly understood. The aim of this
      cohort study was to examine the effect of groin surgery during childhood on the
      incidence and surgical outcome of inguinal hernia repair in adult life. MATERIALS
      AND METHODS:  Data from the Swedish Inpatient Register and the Swedish Hernia
      Register were cross-linked using the patient personal identity numbers. The
      incidence of inguinal hernia repair in patients 15 years or older in the study
      cohort, as well as postoperative complication rates, were compared with the
      expected incidence and complication rates extrapolated from the general Swedish
      population in 2014, stratifying for age and gender. RESULTS:  Note that 68,238
      children aged 0 to 14 years were found to have undergone groin surgery between
      1964 and 1998. The median follow-up time after an operation in the groin was 30.8
      years (21.0-50.0). Of those, 1,118 were found to have undergone inguinal hernia
      repair as adults (> 15 years old) between 1992 and 2013. The incidence of
      inguinal hernia repair in the cohort was significantly higher than that expected
      (1.43 [1.33-1.53]), both for men (1.32 [1.25-1.41]) and women (4.30 [3.28-5.55]).
      The incidence was also increased in the subgroup of patients that had undergone
      more than one procedure during childhood. No significant impact on postoperative
      complication rate, reoperation rate, or operation time was identified.
      CONCLUSION:  Individuals undergoing surgery in the groin during childhood are at
      increased risk for acquired inguinal hernia surgery later in life. Inguinal
      surgery during childhood did not affect the outcome of hernia repair in adult
      age.

PMID- 29653442
TI  - Examination under Anesthesia in Patients with Recurrent Patellar Dislocation:
      Prognostic Study.
AB  - Surgical management of patellar instability is a matter of wide debate. While
      some authors believe that isolated medial patellofemoral ligament (MPFL)
      reconstruction is sufficient, others advocate procedures to treat the underlying
      pathology, namely, patella alta and trochlear dysplasia. Radiological studies
      have been traditionally used as a determinant of these pathologies and to
      determine the need for an additional procedure. The value of examination under
      anesthesia (EUA) in formulating a treatment plan remains unknown. Our aim is to
      assess the prognostic value of EUA in assessing patients presenting for surgical
      treatment of recurrent patellar dislocations. We retrospectively reviewed the
      outcome after surgical treatment of 23 patients who had undergone isolated MPFL
      reconstruction for recurrent patella dislocation by a single surgeon in our
      tertiary center. All data were completed at the time of index surgery. Primary
      outcome was recurrent instability requiring revision surgery. The mean age of the
      23 patients undergoing MPFL reconstruction was 17.4 years of age. The median
      trochlea tuberosity-trochlear groove (TT-TG) distance was 15 mm with a median
      Caton-Deschamps ratio of 1.3. Of the 23 patients who underwent MPFL
      reconstruction, 9 failed (39%). Median time to failure was 10.5 months. All
      patients who failed MPFL reconstruction had a dislocating patella on EUA at >30
      degrees of flexion. Radiological assessment of the knee to assess its morphology
      is essential for preoperative surgical planning for patients with recurrent
      patellar instability. Cutoff values to determine the need for surgical procedures
      require a consistent method of imaging and are prone to flaws in measurement.
      However, we demonstrated that EUA provides valuable additional information toward
      an appropriate surgical approach.Based on our small cohort, we suggest that
      patients in whom patella remains dislocated past 30 degrees of knee flexion on
      EUA are unlikely to benefit from isolated MPFL reconstruction.

PMID- 29653443
TI  - The Role of Clinical Examination in Predicting Relevant MRI Findings in Acute
      Knee Injuries: A Retrospective Study.
AB  - The objective of this study was to delineate the usefulness of clinical
      examination and magnetic resonance imaging (MRI) in acute knee injuries. We aim
      to establish whether the time period post acute knee injury is related to the
      diagnostic accuracy of clinical examination and to investigate the strength of
      specific clinical examination findings in predicting a clinically relevant MRI
      abnormality. Seventy patients were referred to fracture clinic with an acute knee
      injury who subsequently went on to be investigated with MRI over 12 months. These
      patients were retrospectively analyzed looking at the time period they were
      reviewed, the components that were assessed at physical examination, and the
      results of their eventual MRI scan looking for any correlation. A greater
      proportion of patients who were examined at 2 weeks had relevant positive
      findings on MRI scan, p = 0.03. Range of movement and lateral joint line
      tenderness were not associated with a positive MRI scan at any period after
      injury. The presence of a moderate to large effusion was not associated with an
      MRI abnormality if the examination was within 2 weeks of injury but was if
      present 2 weeks after injury, p = 0.0001. Range of movement should not form part
      of the decision making on whether an injury should be investigated with MRI.
      Joint effusion in isolation within 2 weeks after injury should not be an
      indication for MRI but a repeat clinical examination in 2 weeks, where if still
      present, should be investigated with MRI.

PMID- 29653444
TI  - Effect of the Distal Femoral Joint Line on Ligament Tensions in Flexion with
      Cruciate-Retaining Total Knee Prostheses.
AB  - Proper ligament tension in knee flexion within cruciate-retaining (CR) total knee
      arthroplasty has long been associated with clinical success; however, traditional
      balancing principles have assumed that the distal femoral joint line (DFJL)
      affects only extension. The purpose of this study was to determine the effect
      DFJL may have on ligament strains and tibiofemoral kinematics of CR knee designs
      in flexion. A computational analysis was performed using a musculoskeletal
      modeling system for two different knee implants, the high-flex CR (HFCR) and
      guided-motion CR (GMCR). Tibiofemoral kinematics and ligament strain were
      measured at 90-degree knee flexion while the implants' DFJL was incrementally
      shifted proximally. Femoral implant position and kinematics were used to
      determine the femur's anteroposterior position relative to the tibia. The change
      in the femoral medial condyle position relative to the tibia was 0.33 mm and 0.53
      mm more anterior per each 1-mm elevation of the DFJL for HFCR and GMCR,
      respectively. The change in the lateral condyle position was 0.20 mm more
      anterior and 0.06 mm more posterior for HFCR and GMCR, respectively. The strain
      in the lateral and medial collateral ligaments changed minimally with elevation
      of the DFJL. In both implants, strain increased in the anterior lateral and
      posterior medial bundles of the posterior collateral ligament with elevation of
      the DFJL, whereas strain decreased in the iliotibial band and iliotibial patellar
      band. Our findings suggest that DFJL affects ligament tension at 90-degree knee
      flexion and therefore flexion balance for CR implants. Elevating the DFJL to
      address tight extension space in a CR knee while flexion space is well balanced
      could result in increased flexion tension especially when the flexion-extension
      mismatch is large. To achieve balanced flexion and extension, the amount of DFJL
      elevation may need to be reduced.

PMID- 29653445
TI  - Revision Anterior Cruciate Ligament Reconstruction Outcomes at a Minimum of 5
      Year Follow-Up: A Systematic Review.
AB  - Revision anterior cruciate ligament (ACL) reconstruction typically has worse
      outcomes than primary reconstructions. Minimal long-term data exist regarding 5
      year results. We chose to perform a systematic review to evaluate midterm (5
      year) revision ACL reconstruction outcomes (patient-reported outcomes,
      reoperation, stability, arthritis) in comparison to primary ACL reconstructions
      at similar time points. Embase, Cochrane, and PubMed databases were queried, and
      four studies met the inclusion criteria. Two authors reviewed and performed data
      extraction. All were level 4 studies. Review of the studies demonstrated that
      results at 5 years are consistently worse than those noted in primary
      reconstructions for objective and patient-reported outcomes. Revision ACL
      reconstruction outcomes remain worse than primary reconstructions at midterm 5
      year follow-up. The level of evidence is 4.

PMID- 29653446
TI  - Successful closure of a gastropulmonary fistula after esophagectomy using the
      Apollo Overstitch and endoscopic vacuum therapy.

PMID- 29653447
TI  - Rendezvous biliary recanalization with combined percutaneous transhepatic
      cholangioscopy and double-balloon endoscopy.

PMID- 29653448
TI  - Closure of a mucosal defect with clips and rubber band: a technical trick to
      improve edge apposition in large mucosal defects.

PMID- 29653449
TI  - Reintervention for stent occlusion after endoscopic ultrasound-guided
      hepaticogastrostomy with novel use of a precut needle-knife.

PMID- 29653450
TI  - The efficacy and feasibility of the beforehand-endoloop technique for colorectal
      endoscopic submucosal dissection.

PMID- 29653451
TI  - Fluoroscopy-guided peroral endoscopic myotomy for sigmoid-type achalasia.

PMID- 29653452
TI  - The Impact of Hypoxemia on the Development of Retinopathy of Prematurity in
      Infants Less Than 29 Weeks of Gestation.
AB  - OBJECTIVE:  To study the impact of cumulative exposure to hypoxemia on the
      development of retinopathy of prematurity (ROP) in preterm infants less than 29
      weeks' gestation. STUDY DESIGN:  This is a retrospective analysis of the effect
      of cumulative exposure to hypoxemia during the first 10 weeks of life in preterm
      infants <29 weeks' gestation. Cumulative time spent at various levels of oxygen
      saturation was calculated by converting the daily percentage of time to minutes
      per day. Cumulative exposure to hypoxemia (cT<80 or oxygen saturation <80%) was
      calculated weekly and compared between outcomes. The primary outcome was the
      development of ROP requiring treatment. RESULTS:  Cumulative hypoxemia exposure
      was significantly associated with ROP requiring treatment. When adjusted for
      other neonatal morbidities, only gestation was consistently associated with ROP
      requiring treatment. CONCLUSION:  Cumulative exposure to hypoxemia in the first
      few weeks was not associated with ROP or treatment of ROP after adjustment for
      confounders.

PMID- 29653453
TI  - [Oral Health-Related Quality of Life in Rare Diseases with Oral Manifestations].
AB  - OBJECTIVES: In 2013 the German Ministry of Health initiated a "National Plan of
      Action for People with Rare Diseases" (NAMSE), in order to improve medical
      treatment for people with rare diseases. The aim of NAMSE is to set up
      appropriate medical care for those affected, as well as to obtain information on
      the current state of care for these patients. The aim of this study was to obtain
      information on the oral health-related quality of life (OHRQoL) of people with
      rare diseases with oral involvement. METHODS: In the context of the NAMSE plan,
      special consultation times were introduced for people with rare diseases with
      oral involvement. Using the standardized OHIP 14 questionnaire, specific
      information was acquired on OHRQoL, as was as general information on the disease
      in question. RESULTS: During consultation hours, 50 people were treated who, on
      average, travelled 143 km each way. On average, patients had to wait 5 years
      before the final diagnosis of their rare disease was reached. The mean OHIP 14
      overall score achieved was 26.4. DISCUSSION: The long distances travelled show
      the effort involved for patients, especially for those who come for a series of
      sessions. This has led to a call for a nationwide system of special consultation
      sessions for rare diseases with oral involvement - something NAMSE has also
      called for. There seems to be a markedly worse OHRQoL among all our patients.
      Overall, rare diseases with oral involvement appear to benefit more from an
      earlier diagnosis of the disease than do rare diseases without any oral
      involvement.

PMID- 29653454
TI  - How Does Autologous Breast Reconstruction Impact Downtime?
AB  - BACKGROUND:  Although autologous breast reconstruction is technically quite
      demanding, it offers the best outcomes in terms of durable results, patient
      perceptions, and postoperative pain. Many studies have focused on clinical
      outcomes and technical aspects of such procedures, but few have addressed the
      impact of various flaps on patient recovery times. This particular investigation
      entailed an assessment of commonly used flaps, examining the periods of time
      required to resume daily activities. METHODS:  Multiple choice questionnaires
      were administered to 121 patients after recovery from autologous reconstruction
      to determine the times required in returning to specific physical activities. To
      analyze results, the analysis of variance F-test was applied, and odds ratios
      (ORs) were determined. RESULTS:  Among the activities surveyed, recovery time was
      not always a function of free-flap surgery. Additional treatments and
      psychological effects also contributed. Adjuvant chemotherapy increased average
      downtime by 2 weeks, and postoperative irradiation prolonged recovery as much as
      4 weeks. Patient downtime was unrelated to flap type, ranging from 2.9 to 21.3
      weeks for various activities in question. Deep inferior epigastric perforator
      (DIEP) flaps yielded the highest OR and transverse upper gracilis (TUG) flaps the
      lowest. CONCLUSION:  Compared with superior gluteal artery perforator and TUG
      flaps, the DIEP flap was confirmed as the gold standard in autologous breast
      reconstruction, conferring the shortest recovery times. All adjuvant therapies
      served to prolong patient recovery as well. Surgical issues, patient lifestyles,
      and donor-site availability are other important aspects of flap selection.

PMID- 29653455
TI  - Identification, Isolation and Determination of Biomarkers for Quality Control of
      Bush Tea (Athrixia phyllicoides).
AB  - Athrixia phylicoides, known as "bush tea", grows abundantly in South Africa. An
      infusion of the leaves is used as a beverage and to treat a multitude of health
      conditions. The aim of this study was to investigate the chemical variation
      within A. phylicoides and to identify characteristic compounds for quality
      control. Samples from 12 locations in South Africa were analysed using ultra
      performance liquid chromatography. Hierarchical cluster analysis of the aligned
      ultra-performance liquid chromatography-time-of-flight mass spectrometry data
      indicated two groups on the resulting dendrogram, representing 48 samples. Five
      marker compounds, identified through visual inspection and the construction of a
      discriminant analysis model, were evident on the ultra-performance liquid
      chromatography-MS profiles. Four of these compounds were isolated and identified,
      three as hydroxy methoxyflavones and the fourth as a coumarate, using nuclear
      magnetic resonance spectroscopy. An ultra-performance liquid chromatography
      photodiode array method was developed and validated for the determination of the
      marker compounds using the isolates as standards. The limits of detection for the
      four compounds ranged from 0.92 - 2.50 ug/mL. Their recoveries at three
      concentration levels (1.00, 10.0, and 100 ug/mL) were between 97.0 and 101%,
      while acceptable intra- and inter-day precision was obtained as reflected by
      percentage relative standard deviation values below 2.24%. The concentrations of
      all the marker compounds were found to be higher in samples corresponding to
      Group 1 of the dendrogram than in those from Group 2. This may be attributable to
      differences in altitude, climate, and some edaphic factors. Identification of
      these marker compounds will make a valuable contribution towards the quality
      control and sustainable commercialisation of bush tea.

PMID- 29653456
TI  - Hesperidin Prevents High Glucose-Induced Damage of Retinal Pigment Epithelial
      Cells.
AB  - The present study aimed to determine whether hesperidin, a plant-based active
      flavanone found in citrus fruits, can prevent high glucose-induced retinal
      pigment epithelial (RPE) cell impairment. Cultured human RPE cells (ARPE-19) were
      exposed to a normal glucose concentration (5.5 mM) for 4 d and then soaked in
      either normal (5.5 mM) or high (33.3 mM) concentrations of D-glucose with or
      without different concentrations of hesperidin (10, 20, or 40 uM) for another 48
      h. The survival rates of the cells were measured using a 3-(4,5-dimethyl thiazol
      2-yl)-2,5-diphenyl tetrazolium bromide reduction assay. With the help of a
      fluorescent probe, the intracellular production of reactive oxygen species (ROS)
      was evaluated. Colorimetric assay kits were used to assess the antioxidant enzyme
      activities, and western blotting was used to measure the expression of apoptosis
      related protein. Hesperidin was effective in inhibiting high glucose-induced ROS
      production, preventing loss of cell viability, and promoting the endogenous
      antioxidant defense components, including glutathione peroxidase, superoxide
      dismutase, catalase, and glutathione, in a concentration-dependent manner.
      Furthermore, high glucose triggered cell apoptosis via the upregulation of
      caspase-9/3, enhancement of cytochrome c release into the cytosol, and subsequent
      interruption of the Bax/Bcl-2 balance. These detrimental effects were ameliorated
      by hesperidin in a concentration-dependent manner. We conclude that through the
      scavenging of ROS and modulation of the mitochondria-mediated apoptotic pathway,
      hesperidin may protect RPE cells from high glucose-induced injury and thus may be
      a candidate in preventing the visual impairment caused by diabetic retinopathy.

PMID- 29653457
TI  - Difficulties in Differentiating Natural from Synthetic Alkaloids by Isotope Ratio
      Monitoring using 13C Nuclear Magnetic Resonance Spectrometry.
AB  - Within the food and pharmaceutical industries, there is an increasing legislative
      requirement for the accurate labeling of the product's origin. A key feature of
      this is to indicate whether the product is of natural or synthetic origin. With
      reference to this context, we have investigated three alkaloids commonly
      exploited for human use: nicotine, atropine, and caffeine. We have measured by
      13C nuclear magnetic resonance spectrometry the position-specific distribution of
      13C at natural abundance within several samples of each of these target
      molecules. This technique is well suited to distinguishing between origins, as
      the distribution of the 13C isotope reflects the primary source of the carbon
      atoms and the process by which the molecule was (bio)synthesized. Our findings
      indicate that labeling can be misleading, especially in relation to a supplied
      compound being labeled as "synthetic" even though its 13C profile indicates a
      natural origin.

PMID- 29653458
TI  - [Assessment of Couples' Communication in Patients with Advanced Cancer:
      Validation of a German Version of the Couple Communication Scale (CCS)].
AB  - BACKGROUND: There are only a few valid instruments measuring couples'
      communication in patients with cancer for German speaking countries. The Couple
      Communication Scale (CCS) represents an established instrument to assess couples'
      communication. However, there is no evidence regarding the psychometric
      properties of the German version of the CCS until now and the assumed one factor
      structure of the CCS was not verified for patients with advanced cancer yet.
      METHOD: The CCS was validated as a part of the study "Managing cancer and living
      meaningfully" (CALM) on N=136 patients with advanced cancer (>=18 years, UICC
      state III/IV). The psychometric properties of the scale were calculated (factor
      reliability, item reliability, average variance extracted [DEV]) and a
      confirmatory factor analysis was conducted (Maximum Likelihood Estimation). The
      concurrent validity was tested against symptoms of anxiety (GAD-7), depression
      (BDI-II) and attachment insecurity (ECR-M16). RESULTS: In the confirmatory factor
      analysis, the one factor structure showed a low, but acceptable model fit and
      explained on average 49% of every item's variance (DEV). The CCS has an excellent
      internal consistency (Cronbachs alpha=0,91) and was negatively associated with
      attachment insecurity (ECR-M16: anxiety: r=- 0,55, p<0,01; avoidance: r=- 0,42,
      p<0,01) as well as with anxiety (GAD-7: r=- 0,20, p<0,05) and depression (BDI-II:
      r=- 0,27, p<0,01). CONCLUSION: The CCS is a reliable and valid instrument
      measuring couples' communication in patients with advanced cancer.

PMID- 29653459
TI  - [Cultural Influence on Attitude towards Psychotherapy - A Comparison of
      Individuals of Turkish Origin with Individuals without Migration Background].
AB  - AIM: The present study compares the attitude towards psychotherapy of persons
      living in Germany with or without Turkish background. In this context, gender
      related, disorder-specific and sociodemographic differences in openness towards
      psychotherapy are taken into account. METHODS: Individuals of Turkish origin
      (n=129) and individuals without migration background (n=129) were interviewed
      with the Questionnaire on Attitudes towards Psychotherapeutic Treatment, the
      Social Support Questionnaire, a short version of the Symptom-Checklist with the
      subscales anxiety, depression and somatization, and a sociodemographic
      questionnaire. RESULTS: The attitude towards psychotherapy is less positive in
      Turkish migrants than in people without migration background. Females, depressive
      individuals, persons with high social support, with children and a high level of
      education are more open towards psychotherapy. DISCUSSION: The attitude towards
      psychotherapy is influenced by gender, socio-demographic and disorder-specific
      factors and in particular by cultural factors. CONCLUSION: These results
      elucidate the need for better information about psychotherapy and the development
      of intercultural consulting services for migrants in Germany.

PMID- 29653460
TI  - [Doctor-Patient Communication Training in Simulated Situations: Emotions and
      Perceptions of Simulated Patients during Patient-Centered Conversations].
AB  - INTRODUCTION: The use of simulated patients (SPs) for doctor-patient
      communication training has been established in medical curricula as an important
      didactic method. The study addresses the question, if patients' emotions and
      perceptions are represented adequately in patient-centered communication.
      MATERIALS AND METHODS: 22 of 37 SPs of the Medical University of Vienna (12
      women, 10 men) were asked openly about their feelings after having acted as an SP
      in a semi-structured interview, which employed the Critical Incident Technique.
      The interviews were recorded, transcribed, separated into situational analysis
      units und analyzed deductively; we used the evidence based qualities of patient
      centered communication and the "Nationaler Kompetenzbasierter Lernzielkatalog
      Medizin" as a guideline. RESULTS: Out of 192 analysis units, 67 were evaluated as
      positive and 125 as negative. The SPs reported positive feelings, such as
      perceiving "stability and trust in relationships" (22%), perception of congruence
      (15%), acceptance (27%) and empathy (36%). As to negative feelings, SPs reported
      "perceiving instability" (18%), "incongruence" (11%), "lack of acceptance" (40%)
      and "lack of empathy" (30%). Additionally, 50% of SPs were positively affected
      when observing students' learning success. DISCUSSION: When SPs perceived patient
      centered communication, they reported positive emotions. A lack of patient
      centeredness, on the contrary, provoked negative emotions. An empathic attitude,
      as well as a "lack of acceptance" with contrary effects had the strongest
      influence on the SPs' mental state. The reaction of SPs to patient centeredness
      is sufficiently authentic to reach learning objectives, however it is also
      affected by reactions of SPs to the learning success of students, which is
      irrelevant for the real-life doctor-patient interaction. CONCLUSION: SP reactions
      are affected by students' attitudes. Students should therefore be prepared well
      before interacting with SPs in a roleplay setting. While SPs' behavior is
      authentic in patient-centered communication in general, SPs should be trained to
      hide their positive emotions concerning students' learning success during
      roleplay.

PMID- 29653461
TI  - [Users' Experiences with Psychosocial Counselling Services in a Community Mental
      Health Centre].
AB  - OBJECTIVE: Analysis of users experiences with a low-threshold psychosocial
      counselling and case management service across separate sectors (e. g.,
      outpatient, inpatient) and legal provisions (e. g., V and XII Books of Social
      Code). METHODS: Nine semi-structured interviews were conducted and analysed using
      content analysis. RESULTS: Several aspects of the users' experiences with
      counselling services have contributed towards their satisfaction with the
      service. The importance of short waiting times and the on-call telephone service
      as well as sufficient time taken for consultations, the availability of outreach
      counselling and the quality of the relationship with the counsellor were all
      highlighted. Potential for improvement was seen in the visibility of the service
      in the community. CONCLUSION: The investigated counselling and case management
      service can help to provide a low-threshold crisis intervention and could place
      users in more custom-fit community integration services.

PMID- 29653462
TI  - Docosahexaenoic acid reversed atherosclerotic changes in human endothelial cells
      induced by palmitic acid in vitro.
AB  - : Abnormal activity of atherosclerotic endothelial cells paving luminal surface
      of blood vessels has been described in many diseases. It has been reported that
      natural polyunsaturated fatty acids such as docosahexaenoic acid exert
      therapeutic effects in atherosclerotic condition. Human umbilical vein
      endothelial cells were treated with 1mM palmitic acid for 48 hours and exposed to
      40MUM docosahexaenoic acid for the next 24 hours. Real-time polymerase chain
      reaction analysis was used to measure the expression of PTX3, iNOS, and eNOS. The
      level of nitric oxide was detected by Griess reagent. The transcription level of
      genes participating in coagulation and blood pressure was studied by polymerase
      chain reaction array. Docosahexaenoic acid improved the survival rate by reducing
      apoptosis rate (P < .05). Compared with that of the group given palmitic acid,
      attenuation of proinflammatory status was indicated by reduced interleukin-6 (P <
      .05) and prostaglandin E2 levels. All genes PTX3, iNOS, and eNOS were down
      regulated after being exposed to docosahexaenoic acid. Nitric oxide contents were
      not changed in cells exposed to docosahexaenoic acid. Polymerase chain reaction
      array confirmed the reduction of LPA, PDGFbeta, ITGA2, SERPINE1, and FGA after
      exposure to docosahexaenoic acid for 24 hours (P < .05). Docosahexaenoic acid had
      potential to blunt atherosclerotic changes in the modulation of genes controlling
      blood coagulation, pressure, and platelet function. SIGNIFICANCE OF THE STUDY:
      The current experiment showed that docosahexaenoic acid could reverse
      atherosclerotic changes in human endothelial cells induced by palmitic acid. The
      increased levels of interleukin-6 and prostaglandin E2 in atherosclerotic cells
      were returned to near-to-normal status. Gene expression analysis showed a reduced
      activity of genes participating in atherosclerotic endothelial cells treated by
      docosahexaenoic acid. The expression of genes related to cell clotting activity
      was also similar to that of normal cells.

PMID- 29653463
TI  - Estimation of glycaemic control in the past month using ratio of glycated albumin
      to HbA1c.
AB  - AIMS: To evaluate comprehensively the use of the glycated albumin to HbA1c ratio
      for estimation of glycaemic control in the previous month. METHODS: A total of
      306 children with Type 1 diabetes mellitus underwent >=10 simultaneous
      measurements of glycated albumin and HbA1c . Correlation and concordance rates
      were examined between HbA1c measurements taken 1 month apart (DeltaHbA1c ) and
      glycated albumin/HbA1c ratio fluctuations were calculated as Z-scores from the
      cohort value at enrolment of this study cohort (method A) or the percent
      difference from the individual mean over time (method B). RESULTS: Fluctuations
      in glycated albumin/HbA1c ratio (using both methods) were weakly but
      significantly correlated with DeltaHbA1c , whereas concordance rates were
      significant for glycaemic deterioration but not for glycaemic improvement.
      Concordance rates were higher using method B than method A. CONCLUSIONS: The
      glycated albumin/HbA1c ratio was able to estimate glycaemic deterioration in the
      previous month, while estimation of glycaemic improvement in the preceding month
      was limited. Because method B provided a better estimate of recent glycaemic
      control than method A, the individual mean of several measurements of the
      glycated albumin/HbA1c ratio over time may also identify individuals with high or
      low haemoglobin glycation phenotypes in a given population, such as Japanese
      children with Type 1 diabetes, thereby allowing more effective diabetes
      management.

PMID- 29653466
TI  - Diabetes research in primary care: fiction, reality or essential?

PMID- 29653464
TI  - MicroRNA-130b targets PTEN to induce resistance to cisplatin in lung cancer cells
      by activating Wnt/beta-catenin pathway.
AB  - More and more studies indicate the relevance of miRNAs in inducing certain drug
      resistance. Our study aimed to investigate whether microRNA-130b-3p (miR-130b)
      mediates the chemoresistance as well as proliferation of lung cancer (LC) cells.
      MTS assay and apoptosis analysis were conducted to determine cell proliferation
      and apoptosis, respectively. Binding sites were identified using a luciferase
      reporter system, whereas mRNA and protein expression of target genes was
      determined by RT-PCR and immunoblot, respectively. Mouse xenograft model was used
      to evaluate the role of miR-130b in cisplatin resistance in vivo. The rising
      level of miR-130b in cisplatin resistance LC cell lines (A549/CR and H446/CR)
      versus its parental cell lines, indicated its crucial relevance for LC biology.
      We identified PTEN as miR-130b's major target and inversely correlated with miR
      130b expression in LC. Moreover, excessive miR-130b expression promoted drug
      resistance and proliferation, decreased apoptosis of A549 cells. Suppression of
      miR-130b enhanced drug cytotoxicity and reduced proliferation of A549/CR cells
      both internally and externally. Particularly, miR-130b mediated Wnt/beta-catenin
      signalling pathway activities, chemoresistance and proliferation in LC cell,
      which was partially blocked following knockdown of PTEN. These findings suggest
      that miR-130b targets PTEN to mediate chemoresistance, proliferation, and
      apoptosis via Wnt/beta-catenin pathway. The rising level of miR-130b in cisplatin
      resistance LC cell lines (A549/CR and H446/CR) versus its parental cell lines,
      indicated its crucial relevance for LC biology. Moreover, excessive miR-130b
      expression promoted drug resistance and proliferation, decreased apoptosis of
      A549 cells. These findings suggest that miR-130b targets PTEN to mediate
      chemoresistance, proliferation, and apoptosis via Wnt/beta-catenin pathway.

PMID- 29653465
TI  - Steric/pi-Electronic Insulation of the carbo-Benzene Ring: Dramatic Effects of
      tert-Butyl versus Phenyl Crowns on Geometric, Chromophoric, Redox, and Magnetic
      Properties.
AB  - Hexa-tert-butyl-carbo-benzene (C18 tBu6 ) and three phenylated counterparts (C18
      tBum Ph6-m ; m=4, 2) have been synthesized. The peralkylated version (m=6)
      provides experimental access to intrinsic features of the insulated C18 core
      independently from the influence of pi-conjugated substituent. Over the series,
      structural, spectroscopic, and electrochemical properties are compared with those
      of the hexaphenylated reference (m=0). Anchoring tBu substituents at the C18
      macrocycle is shown to enhance stability and solubility, and to dramatically
      modify UV/Vis absorption and redox properties. Whereas all carbo-benzenes
      reported previously were obtained as dark-reddish/greenish solids, crystals and
      solutions of C18 tBu6 happen to be yellow (lambdamax =379 vs. 472 nm for C18 Ph6
      ). In comparison to C18 Ph6 , the reduction of C18 tBu6 remains reversible, but
      occurs at twice as high an absolute potential (E1/2 =-1.36 vs. -0.72 V).
      Systematic XRD analyses and DFT calculations show that the C18 ring symmetry is
      the nearest to D6h for m=6, which indicates a maximum geometric aromaticity.
      According to calculated nucleus-independent chemical shifts (NICS), the
      macrocyclic magnetic aromaticity is also maximum for C18 tBu6 : NICS(0)=-17.2 ppm
      versus (-18.0+/-0.1) ppm for the theoretical references C18 H6 and C18 F6 , and 
      13.5 ppm for C18 Ph6 . Accurate correlations of NICS(0) with experimentally
      recorded or calculated maximum UV/Vis absorption wavelengths, lambdamax , and
      chemical hardness, eta=ELUMO -EHOMO , are evidenced.

PMID- 29653467
TI  - Biomarkers, omics, and the curve.

PMID- 29653468
TI  - Use of fixed ratios in mixture studies, in vitro evidence of issues.

PMID- 29653469
TI  - Professionalism in integrated environmental assessment and management.

PMID- 29653470
TI  - Differences in vitellogenin production between laboratory-raised and wild fathead
      minnows: Potential consequences for understanding estrogenic exposure in wild
      populations.

PMID- 29653472
TI  - Learned Discourses: Timely Scientific Opinions.

PMID- 29653471
TI  - In a Nutshell.

PMID- 29653473
TI  - Characterization of Carbapenemase-Producing Enterobacteriaceae from Patients in
      Amman, Jordan.
AB  - We sought to detect and determine the genetic diversity of carbapenemase
      producing Enterobacteriaceae (CPE) isolated from clinical specimens in Amman,
      Jordan. From five hospitals, a total of 2,759 isolates had antimicrobial
      susceptibilities determined via Vitek II, of which 28 (1%) were carbapenem
      resistant. Species identifications were determined via matrix-assisted laser
      desorption ionization time-of-flight mass spectrometry and carbapenemase gene
      detection via real-time PCR indicated that 23 (82.1%) isolates were Klebsiella
      pneumoniae (OXA-48-like, n = 7; NDM, n = 14; OXA-48-like and NDM, n = 2), four
      (14.2%) were Enterobacter cloacae complex (NDM, n = 3 and VIM, n = 1), and one
      (3.5%) was Escherichia coli (NDM). Sequencing of carbapenemase gene amplicons
      from a subset of isolates identified blaNDM-1, blaOXA-48, and blaVIM-4 alleles.
      Strain typing detected seven different K. pneumoniae variable number tandem
      repeat types, consistent with mostly sporadic occurrences along with limited
      clonal spread. E. cloacae complex isolates were diverse by pulsed-field gel
      electrophoresis, with a maximum relatedness of 70%. Plasmid restriction fragment
      length polymorphism (pRFLP) revealed four distinct profiles associated with NDM
      encoding plasmids that were positive for replicons of the FII(K)/FIB or FIB
      incompatibility (Inc) groups via PCR-based replicon typing. OXA-48-encoding
      IncL/M plasmids differed by two pRFLP bands. The results show diverse CPE produce
      OXA-48 and NDM-1 enzymes in Jordan and that the carbapenemase genes are
      distributed on diverse plasmids in Jordanian hospitals, with some limited
      evidence for related clusters occurring, emphasizing the need for strict
      infection control measures.

PMID- 29653474
TI  - Antimicrobial Susceptibility Patterns of Brachyspira Species Isolated in Taiwan.
AB  - Some members of the Brachyspira genus cause diseases such as swine dysentery (SD)
      and porcine intestinal (or colonic) spirochetosis. Severe economic losses are
      caused by decreased feed intake and increased feed conversion ratio, as well as
      costs associated with treatment and death. A loss of clinical efficacy of some
      antimicrobial agents authorized for treating SD has been observed in many
      countries. The aim of this study was to analyze the antimicrobial susceptibility
      of Brachyspira isolated from Taiwan and to investigate the mechanism of decreased
      susceptibility to macrolides. A total of 55 Brachyspira isolates obtained from
      the grower-finisher period were evaluated in this study. These isolates included
      B. hyodysenteriae (n = 37), B. murdochii (n = 11), B. pilosicoli (n = 5), B.
      intermedia (n = 1), and B. innocens (n = 1). Antimicrobial susceptibility testing
      was performed to examine 12 selected antimicrobial agents. The results showed
      that the 50% and 90% minimum inhibitory concentration (MIC) values of the tested
      macrolides were all >256 MUg/ml. The MIC50 of lincomycin, tiamulin, carbadox,
      olaquindox, ampicillin, amoxicillin, doxycycline, oxytetracycline, and gentamicin
      were 32, 1, <=0.125, <=0.125, 0.5, 0.25, 2, 2, and 2 MUg/ml. The genetic basis of
      the decreased susceptibility to tylosin and lincomycin in Brachyspira spp. was
      investigated and the results showed a possible connection to the mutations at
      position A2058 and G2032 of the 23S rRNA gene. These findings demonstrated that,
      in Taiwan, there may be a decrease in susceptibility of Brachyspira spp. to
      antimicrobials commonly used for the treatment of SD.

PMID- 29653475
TI  - Plasmid-Mediated Quinolone Resistance in Gram-Negative Pathogens Isolated from
      Cancer Patients in Egypt.
AB  - Fluoroquinolones (FQs) are the drugs of choice for prophylaxis of bacterial
      infections in immunocompromised cancer patients. This study aimed to investigate
      FQ resistance and the prevalence of plasmid-mediated quinolone resistance (PMQR)
      determinants in 239 Gram-negative isolates collected at a tertiary care cancer
      hospital in Cairo, Egypt. Disc diffusion and broth microdilution tests showed
      that 70.7% of the isolates were nonsusceptible to ciprofloxacin (MIC50 = 64
      MUg/ml). Polymerase chain reaction (PCR) revealed that 53.6% of the isolates
      carried at least one PMQR determinant, of which 23.4% were susceptible to
      ciprofloxacin. The most prevalent gene, aac(6')-Ib-cr, was identified in 36.8% of
      the isolates, while qnr genes were harbored by 31.0% (qnrS, 24.3%; qnrB, 7.1%,
      and qnrA, 0.4%). The oqxAB genes were only detected in Klebsiella sp. isolates
      (92.5%). PMQR determinants were more likely detectable among isolates recovered
      from pediatric patients than adults (59.3% vs. 43.8%) and were significantly
      associated with ceftriaxone and gentamicin resistance. A combined genetic
      analysis using random amplified polymorphic DNA-PCR and enterobacterial
      repetitive intergenic consensus-PCR showed that most of the qnr-positive isolates
      were not clonal. Findings of the current study raised concerns about the efficacy
      of prophylactic use of FQs in cancer patients in our region. It also demonstrates
      the possible role of PMQR-positive ciprofloxacin-susceptible isolates in the
      dissemination of resistance to other antimicrobial agents and the urgent need to
      reconsider the existing FQ breakpoints defined by the Clinical and Laboratory
      Standards Institute.

PMID- 29653476
TI  - Evaluation of Different Screening Methodologies for the Detection of Methicillin
      Resistant Staphylococcus aureus from Environmental Surfaces: Swabs, Gauzes, and
      Polywipes.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) can survive for long periods
      on inanimate objects, and therefore, environmental surfaces constitute an
      important reservoir for dissemination. However, there is no standardized method
      for the detection of MRSA from environmental surfaces. The aim of the present
      study was to evaluate different screening methods to detect environmental MRSA
      contamination. A total of 294 samples were obtained from inanimate surfaces at a
      hospital in Luanda, Angola, and a hospital in Sao Tome and Principe, by three
      different methodologies: (1) sterile swabs moistened in saline solution, (2)
      sterile cotton gauzes moistened in tryptic soy broth, and (3) commercial
      premoistened sterile sponges (polywipes). After a broth enrichment step, all
      samples were plated onto tryptic soy agar and chromogenic selective media for S.
      aureus and for MRSA. The S. aureus isolates were characterized by pulsed-field
      gel electrophoresis, spa typing, multilocus sequence typing, and SCCmec typing.
      Comparing the three screening methods, gauzes were the most effective (16 S.
      aureus out of 98 samples; 16.3%), followed by polywipes (4/98; 4.1%) and swabs
      (3/98; 3.1%). Moistened gauzes were the most sensitive method (p < 0.00001),
      while screening with swabs was the least efficient (p = 0.00002). The majority of
      the MRSA isolates (75%) belonged to the main clonal types previously found among
      patients and healthcare workers in the same hospitals: ST5-IVa (n = 7; 44%) and
      ST88-IVa (n = 5; 31%). The finding of MRSA on environmental surfaces is dependent
      on the screening methodology. Moistened gauzes followed by a broth enrichment
      step proved to be the most sensitive methodology compared to polywipes and swabs.

PMID- 29653477
TI  - Porin Deficiency in Carbapenem-Resistant Enterobacter aerogenes Strains.
AB  - PURPOSE: The more frequent reports of carbapenem-resistant Enterobacteriaceae
      have raised the alarm for public health. Apart from the production of
      carbapenemases, deficiency (decreased or loss of expression) of outer membrane
      proteins (OMPs) has been proposed as a potentially important mechanism of
      carbapenem resistance. The aim of the present study was to evaluate the
      contribution of the major OMPs to carbapenem resistance in Enterobacter aerogenes
      (CREA) isolates and also investigate the role of small RNAs (sRNAs) in inducing
      porin-associated permeability defects. MATERIALS AND METHODS: The differential
      expression of OMPs was analyzed in four clinical CREA isolates. omp35 and omp36
      genes were further investigated by whole-genome sequencing, induction of
      meropenem resistance, sRNA overexpression, OMP complementation assays, and
      reverse transcription-quantitative PCR. RESULTS: All four isolates examined were
      deficient in omp35 and omp36. Functional restoration of these two genes confirmed
      their contribution to carbapenem resistance. The meropenem induction assay
      further revealed that porin deficiency plays a role in carbapenem resistance
      under antibiotic selection pressure. Single-point mutations in omp36 leading to
      premature stop codons were detected in two of the isolates. Elevated expression
      levels of the sRNAs micF and micC were detected in the other two porin-deficient
      isolates, which were predicted to be potential porin regulators from whole-genome
      sequencing. Overexpression of micF and micC downregulated the expression of Omp35
      and Omp36, respectively. CONCLUSIONS: Porin deficiency plays an important role in
      carbapenem resistance among clinical E. aerogenes isolates under regulation of
      the sRNAs micC and micF. Furthermore, overexpression of micC and micF had a minor
      to no impact on carbapenem minimum inhibitory concentrations, and thus, the
      regulatory mechanism is likely to be complex.

PMID- 29653478
TI  - Mupirocin at Subinhibitory Concentrations Induces Biofilm Formation in
      Staphylococcus aureus.
AB  - OBJECTIVES: Mupirocin is a useful antibiotic against superficial skin infections.
      We compared the impact of mupirocin with a cephalosporin, a fluoroquinolone, an
      aminoglycoside, and a macrolide on planktonic cell growth and biofilm formation
      of methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant
      S. aureus (MRSA). MATERIALS AND METHODS: Minimum inhibitory concentration (MIC)
      of mupirocin was determined against S. aureus strains used in this study. Biofilm
      formation of S. aureus strains exposed to mupirocin was quantified by crystal
      violet staining assay. Moreover, biofilm structure and viability of the biofilm
      cells were visualized by Live/Dead staining assay. Biofilm-related gene
      expression was investigated by quantitative real-time PCR. RESULTS: MRSA USA300
      clone was resistant to mupirocin with MIC of 1,024 mg/L, while MRSA ATCC-43300
      and MSSA ATCC-29213 were susceptible with MICs of 0.03 mg/L. Planktonic cell
      growth of the S. aureus strains was inhibited by mupirocin in a dose-dependent
      manner. However, some of the low concentrations of mupirocin less than the MICs
      promoted biofilm formation. Confocal laser scanning microscopy of the biofilm
      structures and cell viabilities showed established biofilms of slightly higher
      cell density in the mupirocin treated groups, especially in the MRSA USA300
      clone. Gene expression of RNAIII in planktonic cells and biofilms of MRSA USA300
      clone showed the highest upregulation after initial exposure to sub-MIC of
      mupirocin followed by downregulation, whereas the other antibiotics showed
      various fluctuations. CONCLUSION: The results showed that subinhibitory
      concentrations of mupirocin promoted biofilm formation of S. aureus, in
      particular the MRSA USA300 clone.

PMID- 29653480
TI  - Changes in Macrolide Resistance Among Group A Streptococci in Serbia and Clonal
      Evolution of Resistant Isolates.
AB  - In Serbia, the frequency of macrolide-resistant group A streptococci (MRGASs)
      increased significantly from 2006 to 2009. MRGAS analysis in 2008 revealed the
      presence of three major clonal lineages: emm75/mefA, emm12/mefA, and emm77/ermTR.
      The aim of the present study was to determine the prevalence of macrolide
      resistance and to evaluate variations in the clonal composition of MRGASs. The
      study included 1,040 pharyngeal group A streptococci collected throughout Serbia,
      which were tested for antimicrobial susceptibility. MRGAS isolates were further
      characterized by the presence of resistance determinants, emm typing, and pulsed
      field gel electrophoresis analysis. The prevalence of macrolide resistance was
      9.6%, showing a slight decrease compared with the rate of 12.5% (2008).
      Tetracycline resistance was present in 6% of isolates, while norfloxacin
      nonsusceptibility detected for the first time in Serbia was 9.8%. The M phenotype
      dominated (84%), followed by the constitutive macrolides, lincosamides, and
      streptogramin B phenotype (12%). Five emm types were detected: emm75, emm12,
      emm1, emm28, and emm89. The emm75/mefA (62%), emm12/mefA (14%), and
      emm12/ermB/tetM (6%) were predominant clones and were found in both the present
      and the previous study periods at different frequencies. The major change was the
      loss of emm77/ermTR/tetO, which contributed to 15% of MRGASs in 2008.

PMID- 29653479
TI  - Antimicrobial Susceptibility and Enterotoxin-Encoding Genes in Staphylococcus
      spp. Recovered from Kitchen Equipment from a University Hospital in Rio de
      Janeiro, Brazil.
AB  - This study was conducted to determine the occurrence of antimicrobial resistance
      and enterotoxin-encoding genes (EEGs) in Staphylococcus spp. recovered from
      equipment used to prepare hospital meals, in a university hospital in Rio de
      Janeiro, Brazil. Sixty samples were collected from semi-industrial equipment (one
      blender and one mixer) in the hospital's kitchen. Resistance genes and SCCmec
      types were detected by PCR. From the 40 isolates of Staphylococcus spp.
      identified, 8 were Staphylococcus aureus. Thirty-two (80%) Staphylococcus spp.
      isolates were resistant to at least one antimicrobial agent. Resistance genetic
      determinants were detected: erm gene (Staphylococcus epidermidis [n = 2];
      Staphylococcus hominis [n = 1]), mecA gene (S. epidermidis [n = 2]), and aa(6')
      aph(2'') gene (Staphylococcus caprae [n = 1], S. epidermidis [n = 2], S. hominis
      [n = 1], Staphylococcus pausteri [n = 1], Staphylococcus simulans [n = 1], and
      Staphylococcus warneri [n = 1]). The presence of at least one EEG in 83% (n = 33)
      of the isolates was identified. Two strains of S. epidermidis were methicillin
      resistant S. epidermidis (MRSE) and harboring SCCmec type IV. Staphylococcus spp.
      contaminated some hospital kitchen's equipment, indicating that hygiene
      procedures should be improved. Results also indicate that meals can be a vehicle
      to disseminate multiresistant Staphylococcus spp., including MRSE, and
      Staphylococcus with EEGs.

PMID- 29653481
TI  - ISAba1 Regulated OXA-23 Carbapenem Resistance in Acinetobacter baumannii Strains
      in Durban, South Africa.
AB  - AIM: This study investigated the molecular mechanisms of resistance to
      carbapenems and cephalosporins in 24 consecutive, multidrug-resistant
      Acinetobacter baumannii (MDRAB) isolates collected between January and April 2015
      by a private sector laboratory in Durban, South Africa. RESULTS: All isolates
      were resistant to all carbapenems tested. blaOXA-23 and blaOXA-51 genes were
      found in 23 isolates, while blaOXA-24, blaOXA-48, and blaOXA-58 were absent in
      all isolates. The most prevalent extended-spectrum beta-lactamase was TEM-116
      (92%). blaADC was present in 83.3% of isolates, of which two were new variants
      with three and five amino acid differences compared to Acinetobacter-derived
      cephalosporinase (ADC)-1, the first at positions 64E -> K, 341N -> T, and 342R ->
      G and the second at positions 24G -> D, 167S -> P, 283R -> F, 341N -> T, and 342R
      -> G, respectively. All isolates were negative for blaPER, blaCMY, blaGES,
      blaKPC, blaCTX-M, and blaSHV. Metallo-beta-lactamase IMP and VIM were absent in
      all isolates, and NDM-1 was present in 1 isolate. ISAba1 was located upstream
      blaOXA-23 in all isolates and upstream blaADC (30, 78, 79, 87 and the ADC
      variants) in 54.2% of the ADC-carrying isolates. None of the isolates had ISAba1
      inserted upstream blaOXA-51 gene. Four isolates were clonally related and showed
      two clusters (A and B), while 20 isolates remained unclustered. There was no
      direct relationship between the clusters and the hospitals they were isolated
      from. CONCLUSIONS: This study reports the first NDM-1-producing carbapenem
      resistant Acinetobacter baumannii isolate in South Africa and highlights the
      presence of OXA-23, the known ADCs (ADC-30, ADC-78, ADC-79, and ADC-87), and two
      new ADC variants associated with ISAba1 from the private health sector in Durban,
      South Africa. The complexity and diversity of MDRAB severely limit treatment
      options.

PMID- 29653482
TI  - The First Report of Phenotypic and Molecular Characterization of Extended
      Spectrum Beta-Lactamase-Producing Uropathogens in Sikkim and Darjeeling Hills of
      India.
AB  - Extended-spectrum beta-lactamase (ESBL)-producing bacteria are a global health
      threat both in hospital and in community settings. The emergence of these
      organisms poses major difficulty in treating infections. This study was carried
      out to assess major ESBL-producing uropathogens in female patients of Sikkim and
      Darjeeling by phenotypic and genotypic methods. Out of 1,516 urine samples, 454
      uropathogens were isolated with a prevalence rate of 29.94%. Among them,
      Escherichia coli (74.3%) was the predominant type followed by Klebsiella
      pneumoniae (20.1%), Pseudomonas aeruginosa (2.4%), and Proteus mirabilis (1.98%).
      Four different ESBL genes were detected in 63 isolates, which included CTX-M (n =
      32), CTX-M+OXA-2 (n = 15), CTX-M-15+OXA-2+TEM (n = 6), OXA-2 (n = 5), TEM+CTX-M
      15 (n = 2), TEM+OXA-2+SHV-76 (n = 2), and TEM (n = 1). All ESBL genes (bla genes)
      were found on a plasmid, which was mostly of HI1, I1, FIA+FIB, FIA, and Y types
      and was horizontally transferable. Among all ESBL genes, blaCTX-M-I5 group was
      the most prevalent. The study of urinary tract infection (UTI) caused by ESBL
      producing bacteria needs to be studied in other high-altitude parts of India to
      understand the actual burden of UTI in the female.

PMID- 29653486
TI  - PDGFR-beta inhibitor slows tumor growth but increases metastasis in combined
      radiotherapy and Endostar therapy.
AB  - BACKGROUND: Pericytes are pivotal mural cells of blood vessels and play an
      essential role in coordinating the function of endothelial cells. Previous
      studies demonstrated that Endostar, a novel endostatin targeting endothelial
      cells, can enhance the effect of radiotherapy (RT). The present study addressed
      whether inhibiting pericytes could potentially improve the efficacy of combined
      RT and Endostar therapy. METHODS: Platelet-derived growth factor beta-receptor
      inhibitor (CP673451) was chosen to inhibit pericytes and RT (12 Gy) was
      delivered. Lewis lung carcinoma-bearing C57BL/6 mice were randomized into 3
      groups: RT, RT + Endo, and RT + Endo + CP673451. Subsequently, tumor microvessel
      density (MVD), pericyte coverage, tumor hypoxia, and lung metastasis were
      monitored at different time points following different therapies. RESULTS:
      Compared to the other two groups, RT + Endo + CP673451 treatment markedly
      inhibited tumor growth with no improvement in the overall survival. Further
      analyses clarified that in comparison to RT alone, RT + Endo significantly
      reduced the tumor MVD, with a greater decrease noted in the RT + Endo + CP673451
      group. However, additional CP673451 accentuated tumor hypoxia and enhanced the
      pulmonary metastasis in the combined RT and Endostar treatment. CONCLUSIONS:
      Tumor growth can be further suppressed by pericyte inhibitor; however, metastases
      are potentially enhanced. More in-depth studies are warranted to confirm the
      potential benefits and risks of anti-pericyte therapy.

PMID- 29653487
TI  - Solute carrier family 34 member 2 overexpression contributes to tumor growth and
      poor patient survival in colorectal cancer.
AB  - Solute carrier family 34 member 2 (SLC34A2) is a well-known sodium-dependent
      phosphate transporter that has recently been linked to cancer development.
      However, its specific oncogenic role remains controversial in numerous human
      malignancies, and is currently unknown in colorectal cancer (CRC). Therefore, in
      this study we firstly used Oncomine database to determine its expression in
      cancer tissues and found it is overexpressed in thyroid, ovarian and renal
      cancer, while it is opposite in lung, breast and pancreas cancer. Using qRT-PCR
      and western blot, we then demonstrated its overexpression in CRC tissues as
      compared with adjacent normal tissues (n = 20). In a retrospective cohort
      enrolling 190 CRC patients, we proved its expression was significantly correlated
      with N stage. Furthermore, high SLC34A2 expression is associated with higher
      postoperative metastasis rate and serves as an independent adverse factor
      affecting patient prognosis. In subgroup analysis, SLC34A2 expression could
      stratify the patient prognosis in stage II and III CRC, but failed in stage IV
      CRC. In cellular assays in vitro, knockdown of SLC34A2 dramatically inhibited the
      proliferation and colony formation, induced the apoptosis and arrests the cell
      cycle progression of HCT-116 CRC cells. In cellular assays in vivo, knockdown of
      SLC34A2 significantly inhibited the growth of xenografts, decreasing Ki-67 and
      proliferating cell nuclear antigen (PCNA) expression and increasing apoptosis
      rate. Taken together, our study indicates SLC34A2 plays a crucial promoting role
      in CRC development and therefore has great potential to be further developed as a
      reliable biomarker for CRC diagnosis and treatment.

PMID- 29653488
TI  - Teroxirone suppresses growth and motility of human hepatocellular carcinoma
      cells.
AB  - AIMS: The prevalent human hepatocellular carcinoma (HCC) is a leading cause of
      global cancer-related mortality. The small molecular weight triepoxide
      derivative, 1,3,5-triazine-2,4,6(1H,3H,5H)-tri-one-1,3,5-tri-(oxiranylmethyl)
      (teroxirone), has been proved effective against the proliferation of lung cancer
      cells. The purpose is to further examine if teroxirone regulate growth and
      metastatic potential of HCC cells with aims at disclosing more of the reaction
      mechanisms. MAIN METHODS: Measurements of cell viability and flow cytometry were
      conducted to test sensitivities of teroxirone against HCC cells. The signaling
      pathway leading to apoptotic death was unraveled by Western blotting analysis.
      The metastatic progression was evaluated by cell-based phenotype assay that
      included migration, invasion, gelatin zymography and wound assay. The in vivo
      drug efficiency was done in immune-deficient mice with the established xenograft
      tumors. KEY FINDINGS: Teroxirone inhibited growth of HCC cells, but not hepatic
      cells. The drug induced apoptosis in HCC cells bearing mutant p53. Pretreatment
      of caspase-3 inhibitor restored cell viabilities by suppressing extrinsic pathway
      mediated cell death. More experiments suggested that sub-apoptotic concentrations
      of teroxirone mitigated migration, invasion and wound healing of HCC cells. The
      drug reduced growth of the xenograft tumors as established in animal models by
      activating apoptotic death. SIGNIFICANCE: The findings asserted that teroxirone
      is an eligible addition to the existing options as an anticancer agent to
      eliminate HCC.

PMID- 29653489
TI  - Sarcodonin G Derivatives Exhibit Distinctive Effects on Neurite Outgrowth by
      Modulating NGF Signaling in PC12 Cells.
AB  - Sarcodonin G, one of the cyathane diterpenoids isolated from the mushroom
      Sarcodon scabrosus, possesses pronounced neurotrophic activity but ambiguous
      mechanical understanding. In this work, sarcodonin G was chosen as a lead
      compound to prepare a series of 19- O-benzoyl derivatives by semisynthesis and
      their neuritogenic activities were evaluated. 6 and 15 (10 MUM) were investigated
      with opposite effects in PC12 cells. 6 exhibited a superior activity to
      sarcodonin G by promoting NGF-induced neurite outgrowth, while 15 showed an
      inhibitory effect. Supportingly, 6 and 15 (20 MUM) significantly induced and
      suppressed neurite extension in primary cultured rat cortical neurons,
      respectively. In mechanism, the two derivatives were revealed to influence NGF
      induced neurite outgrowth in PC12 cells through the regulation of PKC-dependent
      and -independent ERK/CREB signaling as well as the upstream TrkA receptor
      phosphorylation. Furthermore, a possible pattern of interaction among NGF, 6/15
      and TrkA was presented using molecular simulations. It revealed that 6/15 may
      contribute to the stabilization of the NGF-TrkAd5 complex by establishing several
      hydrophobic and hydrogen-bond interactions with NGF and TrkA, respectively. Taken
      together, 6 and 15 modulate PKC-dependent and -independent ERK/CREB signaling
      pathways possibly by influencing the binding affinity of NGF to the receptor
      TrkA, and finally regulate neurite outgrowth in PC12 cells.

PMID- 29653490
TI  - Safety Assessment of Bacillus thuringiensis Insecticidal Proteins Cry1C and Cry2A
      with a Zebrafish Embryotoxicity Test.
AB  - As a result of the large-scale planting of transgenic Bacillus thuringiensis (Bt)
      crops, fish would be exposed to freely soluble Bt insecticidal protein(s) that
      are released from Bt crop tissues into adjacent bodies of water or by way of
      direct feeding on deposited plant material. To assess the safety of two Bt
      proteins Cry1C and Cry2A to fish, we used zebrafish as a representative species
      and exposed their embryos to 0.1, 1, and 10 mg/L of the two Cry proteins until
      132 h post-fertilization and then several developmental, biochemical, and
      molecular parameters were evaluated. Chlorpyrifos (CPF), a known toxicant to
      aquatic organisms, was used as a positive control. Although CPF exposure resulted
      in significant developmental, biochemical, and molecular changes in the zebrafish
      embryos, there were almost no significant differences after Cry1C or Cry2A
      exposure. Thus, we conclude that zebrafish embryos are not sensitive to Cry1C and
      Cry2A insecticidal proteins at test concentrations.

PMID- 29653491
TI  - Highlights of the Structure-Activity Relationships of Benzimidazole Linked
      Pyrrolidines Leading to the Discovery of the Hepatitis C Virus NS5A Inhibitor
      Pibrentasvir (ABT-530).
AB  - Curative interferon and ribavirin sparing treatments for hepatitis C virus (HCV)
      infected patients require a combination of mechanistically orthogonal direct
      acting antivirals. A shared component of these treatments is usually an HCV NS5A
      inhibitor. First generation FDA approved treatments, including the component NS5A
      inhibitors, do not exhibit equivalent efficacy against HCV virus genotypes 1-6.
      In particular, these first generation NS5A inhibitors tend to select for viral
      drug resistance. Ombitasvir is a first generation HCV NS5A inhibitor included as
      a key component of Viekira Pak for the treatment of patients with HCV genotype 1
      infection. Since the launch of next generation HCV treatments, functional cure
      for genotype 1-6 HCV infections has been achieved, as well as shortened treatment
      duration across a wider spectrum of genotypes. In this paper, we show how we have
      modified the anchor, linker, and end-cap architecture of our NS5A inhibitor
      design template to discover a next generation NS5A inhibitor pibrentasvir (ABT
      530), which exhibits potent inhibition of the replication of wild-type genotype 1
      6 HCV replicons, as well as improved activity against replicon variants
      demonstrating resistance against first generation NS5A inhibitors.

PMID- 29653492
TI  - Visual Arts Education improves self-esteem for persons with dementia and reduces
      caregiver burden: A randomized controlled trial.
AB  - A Visual Arts Education program was tested among 26 pairs of persons with
      dementia and their caregivers. Pairs were randomized to Visual Arts Education or
      control groups, and each group met once per week for two months (8 weeks) to
      participate in activities with a trained arts instructor. Groups were assessed at
      baseline, two months, and six months. The Visual Arts Education group received
      instruction and produced a different type of artistic work each week. The
      pedagogical strategy was designed so that each activity was increasingly novel,
      challenging, and complex. The control group viewed slide shows, participated in
      discussions about art, and made paintings. At the six-month follow-up,
      significant improvements in caregiver burden and self-esteem for the persons with
      dementia were found in the Visual Arts Education group. The Visual Arts Education
      pedagogical approach shows the potential for effectiveness for improving quality
      of life for persons with dementia and their caregivers.

PMID- 29653493
TI  - Intrarenal delivery of bFGF-loaded liposome under guiding of ultrasound-targeted
      microbubble destruction prevent diabetic nephropathy through inhibition of
      inflammation.
AB  - Basic fibroblast growth factor (bFGF) has shown great therapeutic effects for
      diabetic nephropathy (DN). However, its clinical applications are limited due to
      its short half-life, low stability and poor penetration. Herein, a bFGF-loaded
      liposome (bFGF-lip) was constructed and combined with ultrasound-targeted
      microbubble destruction (UTMD) to overcome these drawbacks. bFGF-lip exhibited
      spherical morphology with a diameter of 171.1 +/- 14.2 nm and a negative zeta
      potential of -5.15 +/- 2.08 mV, exhibiting a sustained-release profile of bFGF.
      DN rat models were successfully induced by streptozotocin. After treatment with
      bFGF-lip + UTMD, the concentration of bFGF in kidney of DN rats was significantly
      enhanced in comparison with free bFGF treatment. Additionally, the morphology and
      the function of the kidneys were obviously recovered after bFGF-lip + UTMD
      treatment as shown by ultrasonography and histological analyse. The molecular
      mechanism was associated with the inhibition of renal inflammation. After
      treatment with bFGF-lip + UTMD, the activation of NF-kappaB was obviously reduced
      in the renal tissues, and downstream inflammatory mediators including TGF-beta1,
      MCP-1, IL-6 and IL-1beta were also down regulated. In addition, inflammation
      induced cellular apoptosis of renal tubular cells was also significantly
      inhibited by detecting Bax, caspase-3 and Bcl-2. Therefore, bFGF-lip in
      combination with UTMD might be a potential strategy to reverse the progression of
      early DN.

PMID- 29653494
TI  - Renal nerve stimulation identifies aorticorenal innervation and prevents
      inadvertent ablation of vagal nerves during renal denervation.
AB  - PURPOSE: Recently we reported the use of renal nerve stimulation (RNS) during
      renal denervation (RDN) procedures. RNS induced changes in blood pressure (BP)
      and heart rate are not fully delineated yet. We hypothesized that electrical
      stimulation of the sympathetic nerve tissue in the renal artery would lead to an
      increase in BP and vagal stimulation would cause a decrease in BP. We report the
      different patterns of BP and heart rate responses elicited by RNS prior to RDN.
      METHODS: 35 patients with drug-resistant hypertension were included. RNS was
      performed under general anesthesia at four sites in the right and left renal
      arteries, both before and immediately after RDN. RNS-induced BP and heart rate
      changes were monitored. RESULTS: A total of 289 RNS sites in 35 patients were
      analyzed. An increase in systolic BP of >10 mmHg was regarded as a positive BP
      response to RNS. This pattern of response was observed in 180 sites (62%). 86 RNS
      sites (30%) showed an indifferent response with BP changes <=10 mmHg. At 13 sites
      (4.5%) RNS elicited a decrease in BP up to -8 mmHg. However, 10 RNS sites (3.5%)
      showed a pronounced vagal response with hypotension and sinus cycle lengths
      ranging between 4224-10272 milliseconds. These sites were distributed among two
      patients. CONCLUSION: RNS identified sympathetic and parasympathetic nerve tissue
      in the renal arteries. RNS can be potentially used to map nerve bundles and guide
      selective ablation of sympathetic nerve fibers and prevent inadvertent ablation
      of parasympathetic nerve tissue during RDN.

PMID- 29653495
TI  - Effects of high hydrostatic pressure on the overall quality of Pera-Rio orange
      juice during shelf life.
AB  - The effect of high hydrostatic pressure on antioxidant activity, total phenolic
      compounds, physicochemical characteristics, color, pectin methylesterase
      activity, and microbiological count were evaluated during the shelf life of Pera
      Rio orange juice. Pressurized (520 MPa, 60 C, for 360 s), non-processed and
      pasteurized (95 C/30 s) orange juice were compared at zero time of storage.
      Pressurized and pasteurized juices were studied during a refrigerated 90-day
      shelf life. Pressurization did not cause expressive change in physicochemical
      characteristics of Pera-Rio orange juice along shelf life, but significantly
      reduced pectin methylesterase residual activity to 13% and microbiological counts
      below detection levels up to 68 days of storage, with small counts (30.0 * 10
      CFU/mL mesophilic aerobic bacteria and 20.7 * 10 CFU/mL yeast and mold) at 90
      days, capable of ensuring the juice's stability along shelf life. Lightness ( L*)
      and b* values were significantly reduced by high hydrostatic pressure during
      shelf life, while a* values were significantly higher. Ascorbic acid decreased
      around 80% during shelf life. Antioxidant activity remained stable after
      processing and during storage.

PMID- 29653496
TI  - Pigs are useful for the molecular study of bone inflammation and regeneration in
      humans.
AB  - Pigs are used with increased frequency to model different kinds of orthopedic
      surgical conditions. In order to show the full potential of porcine models in
      orthopedic research, it is therefore required to examine the expression of bone
      regulatory genes in pigs affected by orthopedic surgery and compare it to the
      expression in humans and mice as mice, are one of the most applied animal species
      in orthopedics today. In the present study, the local molecular response to
      drilling of a tibial implant cavity, and the subsequent insertion of a steel
      implant was examined in a porcine model. Pigs were euthanized five days after
      drilling of the bone. The molecular response of 73 different genes was analyzed
      using a high-throughput quantitative polymerase chain reaction platform and
      compared to histopathology. Histologically, it was found that bone remodeling was
      initiated on day 5 after surgery and was associated with upregulation of several
      genes involved in bone degradation and formation ( CTSK, ACP5, IBSP, RANK, RANKL
      and COL1A1). Interleukin-6 and several acute-phase proteins (C3, SAA and ITIH4)
      were significantly upregulated, indicating their importance in the initial
      process of healing and osseointegration. All tested bone morphogenic proteins
      (BMP2, -4 and -7) including their inhibitor noggin were also significantly
      upregulated. Surprisingly, vascular endothelial growth factor A was not found to
      be regulated five days after surgery while several other vascular growth factors
      (ANGPT1, ANGPT2 and PTN) were upregulated. The pig was found to be a useful model
      for elucidation of bone regulatory genes in humans.

PMID- 29653497
TI  - Systematic review of surgical training on reperfused human cadavers.
AB  - BACKGROUND: The role of reperfused human cadavers in surgical training has not
      been established. METHODS: Reports describing reperfused human cadaver models in
      terms of simulated surgeries, the use of tools to assess technical competency and
      skills transfer to patients, cadaver status and reperfusion techniques were
      included. RESULTS: Thirty-five reports were included. Most participants practised
      vascular (n = 27), flap (n = 6) and trauma (n = 4) procedures. Training
      progression was evaluated objectively in only two studies. In two publications,
      flap techniques were practised on cadavers and repeated successfully in patients.
      Eighteen studies employed whole bodies. Fresh and embalmed cadavers were both
      used in 17 publications. Most embalmed cadavers were formalin-fixed (n = 10),
      resulting in stiffness. Few trainings were offered on soft Thiel-embalmed
      cadavers (n = 5). Only arteries were reperfused in 20 studies, while in 13
      publications, the arteries and veins were filled. Arteries and/or veins were
      mostly pressurized (n = 21) and arterial flow was generated in 14 studies.
      CONCLUSIONS: Various reperfused human cadaver models exist, enabling practise of
      mainly vascular procedures. Preservation method determines the level of
      simulation fidelity. Thorough evaluation of these models as surgical training
      tools and transfer effectiveness is still lacking.

PMID- 29653498
TI  - Neurotensin-loaded PLGA/CNC composite nanofiber membranes accelerate diabetic
      wound healing.
AB  - Diabetic foot ulcers (DFUs) are a threat to human health and can lead to
      amputation and even death. Recently neurotensin (NT), an inflammatory modulator
      in wound healing, was found to be beneficial for diabetic wound healing. As we
      demonstrated previously, polylactide-polyglycolide (PLGA) and cellulose
      nanocrystals (CNCs) (PLGA/CNC) nanofiber membranes show good cytocompatibility
      and facilitate fibroblast adhesion, spreading and proliferation. PLGA/CNC
      nanofiber membranes are novel materials that have not been used previously as NT
      carriers in diabetic wounds. This study aims to explore the therapeutic efficacy
      and possible mechanisms of NT-loaded PLGA/CNC nanofiber membranes in full
      thickness skin wounds in spontaneously diabetic mice. The results showed that NT
      could be sustained released from NT-loaded PLGA/CNC composite nanofiber membranes
      for 2 weeks. NT-loaded PLGA/CNC composite nanofiber membranes induced more rapid
      healing than other control groups. After NT exposure, the histological scores of
      the epidermal and dermal regeneration and the ratios of the fibrotic area to the
      whole area were increased. NT-loaded PLGA/CNC composite nanofiber membranes also
      decreased the expressions of the inflammatory cytokines IL-1beta and IL-6. These
      results suggest that NT-loaded PLGA/CNC composite nanofiber membranes for
      sustained delivery of NT should effectively promote tissue regeneration for the
      treatment of DFUs.

PMID- 29653499
TI  - Urinary cytokines and mRNA expression as biomarkers of disease activity in lupus
      nephritis.
AB  - Introduction Renal involvement is one of the most serious manifestations of
      systemic lupus erythematosus, but non-invasive assessment of inflammatory
      response in kidneys is challenging. In this study we aimed to validate markers of
      active lupus nephritis (LN) using urine immune profiling. Methods Urine and serum
      cytokines (17-plex array) and urine mRNA expression (~40 immune and glomerular
      injury genes) were measured in LN patients with active disease ( n = 17) during
      remission ( n = 16) and in healthy subjects ( n = 18). Results Urine and serum
      levels of CCL2, CCL5 and CXCL10 were elevated in active LN as compared with
      disease remission (best discrimination for urine CXCL10 and CCL2) and correlated
      with LN activity. In the active disease, urinary cell transcriptome showed marked
      upregulation of proinflammatory cytokines (e.g. TNF, CCL2, CCL5, CXCL10), and
      type-1 immunity-related genes (e.g. CD3G, CD4, TBX21, IFNG). An active pattern of
      gene expression was also observed in four patients in remission, who had
      moderately increased urinary leucocyte count. Two patients from this group
      developed renal exacerbation during the following 3 months. Markers of type-17
      immune axis (e.g. IL-17A) were not significantly increased in active LN.
      Conclusions Active LN patients were characterized by marked increase of
      proinflammatory mediators in the urine. Urine cytokines (CCL2 and CXCL10) and
      type-1 T-cell-related gene markers in the urine sediment had similar diagnostic
      performance in detection of active LN.

PMID- 29653500
TI  - Suspended polyhydroxyalkanoate microspheres as 3D carriers for mammalian cell
      growth.
AB  - Different forms of biopolyester PHBVHHx microspheres were prepared so as to
      compare the mammalian cell behaviors in suspension cultivation system. Based on a
      microbial terpolyester PHBVHHx consisting of 3-hydroxybutyrate (HB), 3
      hydroxyvalerate (HV), and 3-hydroxyhexanoate (HHx), solid microspheres (SMSs),
      hollow microspheres (HMSs), and porous microspheres (PMS) were successfully
      prepared by a modified solvent evaporation method involving gas-in-oil-in-water
      (G1/O/W2) double emulsion, water-in-oil-in-water (W1/O/W2) double emulsion and
      oil-in-water (O/W) single emulsion, respectively. Generally, PMSs have diameters
      ranging from 330 to 400 MUm with pore sizes of 10 to 60 MUm. The pores inside the
      PMSs were found well interconnected compared with PHBVHHx prepared by the
      traditional solvent evaporation method, resulting in the highest water uptake
      ratio. When inoculated with human osteoblast-like cells lasting 6 days, PMS
      showed much better cell attachment and proliferation compared with other less
      porous microspheres due to its large inner space as a 3 D carrier. Cell migration
      towards surface and other interconnected inner pores was clearly observable. Dead
      or apoptotic cells were found more common among less porous SMSs or HMSs compared
      with highly porous PMSs. It is therefore concluded that porous PHBVHHx
      microspheres with larger surface open pores and interconnected inner pores can
      serve as a carrier or scaffold supporting more and better cell growth for either
      injectable purposes or simply supporting cell growth.

PMID- 29653501
TI  - Hepatic alveolar echinococcosis.

PMID- 29653502
TI  - Treatment with troxerutin protects against cisplatin-induced kidney injury in
      mice.
AB  - BACKGROUND: Cisplatin (CP) is a synthetic and anticancer drug, and one of the
      major side effects of CP is nephrotoxicity. This study was done to evaluate the
      renoprotective effects of troxerutin (Tro) in nephrotoxicity induced by CP in
      male mice. METHODS: In this experimental study, 28 male mice were divided
      randomly into four groups. Mice were treated with CP (20 mg/kg, i.p.) then Tro
      (75 and 150 mg/kg/day, po) was administered for three consecutive days. Blood
      samples were collected to determine serum creatinine (Cr) and blood urea nitrogen
      (BUN) levels. The kidney tissues were used for histological examination and
      biochemical assays. Malondialdehyde (MDA) level, superoxide dismutase (SOD) and
      glutathione peroxidase (GPx) activity were assessed in renal tissue. RESULTS:
      Results showed a significant increase in the Cr, BUN and MDA levels and a
      significant decrease in the renal SOD and GPx activity by CP administration.
      Treatment with Tro for three consecutive days attenuated these changes. Also, the
      renoprotective effect of the Tro was confirmed by the histological examination of
      the kidneys. CONCLUSIONS: Our results demonstrated that Tro has protective
      effects against CP-induced nephrotoxicity through improving the biochemical
      indices and the oxidative stress parameters.

PMID- 29653503
TI  - Systematic review of participants' attitudes towards data sharing: a thematic
      synthesis.
AB  - Objectives Data sharing is well established in biological research, but evidence
      on sharing of clinical trial or public health research study data remains
      limited, in particular studies of research participants' perspectives of data
      sharing. This study systematically reviewed international evidence of research
      participants' attitudes towards the sharing of data for secondary research use.
      Methods Systematic search of seven databases, and author-, citation- and
      bibliography-follow up to identify studies examining research participants'
      attitudes towards data sharing. Studies were thematically analysed using NVivo
      v10 to identify recurring themes. Results Nine studies were eligible for
      inclusion. Thematic analysis identified four key themes: (1) benefits of data
      sharing, including benefit to participants or immediate community, benefits to
      the public and benefits to science or research; (2) fears and harms, such as fear
      of exploitation, stigmatization or repercussions, alongside concerns about
      confidentiality and misuse of data; (3) data sharing processes, in particular the
      role of consent in the process; and (4) the relationship between participants and
      research such as trust in different types of research or organization and the
      relationship with the original research team. Conclusions The available
      literature on attitudes towards sharing data from clinical trials or public
      health interventions remains scant. This study has identified four themes
      regarding research participants' attitudes and preferences, which should be
      considered by policy makers, and explored with further research.

PMID- 29653504
TI  - How embedded is public involvement in mainstream health research in England a
      decade after policy implementation? A realist evaluation.
AB  - Objectives To explore how embedded patient and public involvement is within
      mainstream health research following two decades of policy-driven work to
      underpin health research with patient and public involvement in England. Methods
      Realist evaluation using Normalization Process Theory as a programme theory to
      understand what enabled patient and public involvement to be embedded as normal
      practice. Data were collected through a national scoping and survey, and
      qualitative methods to track patient and public involvement processes and impact
      over time within 22 nationally funded research projects. Results In research
      studies that were able to create reciprocal working relationships and to embed
      patient and public involvement this was contingent on: the purpose of patient and
      public involvement being clear; public contributors reflecting research end
      beneficiaries; researchers understanding the value of patient and public
      involvement; patient and public involvement opportunities being provided
      throughout the research and ongoing evaluation of patient and public involvement.
      Key contested areas included: whether to measure patient and public involvement
      impact; seeking public contributors to maintain a balance between being research
      aware and an outsider standpoint seen as 'authentically' lay; scaling-up patient
      and public involvement embedded within a research infrastructure rather than risk
      token presence and whether patient and public involvement can have a place within
      basic science. Conclusions While patient and public involvement can be well
      integrated within all types of research, policy makers should take account of
      tensions that must be navigated in balancing moral and methodological
      imperatives.

PMID- 29653505
TI  - Non-tuberculous Mycobacterium species causing mycobacteriosis in farmed aquatic
      animals of South Africa.
AB  - BACKGROUND: Mycobacteriosis caused by non-tuberculous mycobacteria (NTM), is
      among the most chronic diseases of aquatic animals. In addition, fish
      mycobacteriosis has substantial economic consequences especially in the
      aquaculture and fisheries industry as infections may significantly decrease
      production and trade. Some fish NTM pathogens are highly virulent and zoonotic;
      as such, infection of aquaria with these pathogens is a public health concern. In
      this study, we report isolation of nine different NTM species from sixteen
      aquatic animals including different fish species, frogs and a crocodile. Given
      the clinical significance of Mycobacterium marinum and its close relation to
      Mycobacterium tuberculosis, as well as the significance of ESAT 6 and CFP-10
      secretion in mycobacterial virulence, we analysed the esxA and esxB nucleotide
      sequences of M. marinum isolates identified in this study as well as other
      mycobacteria in the public databases. RESULTS: Mycobacterium shimoidei,
      Mycobacterium marinum, Mycobacterium chelonae, Mycobacterium septicum /M.
      peregrinum and Mycobacterium porcinum were isolated from gold fish, Guppy, exotic
      fish species in South Africa, koi and undefined fish, Knysna seahorse, as well
      Natal ghost frogs respectively, presenting tuberculosis like granuloma. Other NTM
      species were isolated from the studied aquatic animals without any visible
      lesions, and these include Mycobacterium sp. N845 T, Mycobacterium fortuitum, a
      member of the Mycobacterium avium complex, and Mycobacterium szulgai.
      Phylogenetic analysis of mycobacteria, based on esxA and esxB genes, separated
      slow growing from rapidly growing mycobacteria as well as pathogenic from non
      pathogenic mycobacteria in some cases. CONCLUSIONS: Isolation of the different
      NTM species from samples presenting granuloma suggests the significance of these
      NTM species in causing mycobacteriosis in these aquatic animals. The study also
      revealed the potential of esxA and esxB sequences as markers for phylogenetic
      classification of mycobacteria. Observations regarding use of esxA and esxB
      sequences for prediction of potential pathogenicity of mycobacteria warrants
      further investigation of these two genes in a study employing NTM species with
      well-defined pathogenicity.

PMID- 29653506
TI  - The effect of the H-1 scaling factors tau and omega on the structure of H in the
      single-step procedure.
AB  - BACKGROUND: The single-step covariance matrix H combines the pedigree-based
      relationship matrix [Formula: see text] with the more accurate information on
      realized relatedness of genotyped individuals represented by the genomic
      relationship matrix [Formula: see text]. In particular, to improve convergence
      behavior of iterative approaches and to reduce inflation, two weights [Formula:
      see text] and [Formula: see text] have been introduced in the definition of
      [Formula: see text], which blend the inverse of a part of [Formula: see text]
      with the inverse of [Formula: see text]. Since the definition of this blending is
      based on the equation describing [Formula: see text], its impact on the structure
      of [Formula: see text] is not obvious. In a joint discussion, we considered the
      question of the shape of [Formula: see text] for non-trivial [Formula: see text]
      and [Formula: see text]. RESULTS: Here, we present the general matrix [Formula:
      see text] as a function of these parameters and discuss its structure and
      properties. Moreover, we screen for optimal values of [Formula: see text] and
      [Formula: see text] with respect to predictive ability, inflation and iterations
      up to convergence on a well investigated, publicly available wheat data set.
      CONCLUSION: Our results may help the reader to develop a better understanding for
      the effects of changes of [Formula: see text] and [Formula: see text] on the
      covariance model. In particular, we give theoretical arguments that as a general
      tendency, inflation will be reduced by increasing [Formula: see text] or by
      decreasing [Formula: see text].

PMID- 29653507
TI  - No one size fits all-the development of a theory-driven intervention to increase
      in-hospital mobility: the "WALK-FOR" study.
AB  - BACKGROUND: There is growing evidence that mobility interventions can increase in
      hospital mobility and prevent hospitalization-associated functional decline among
      older adults. However, implementing such interventions is challenging, mainly due
      to site-specific constraints and limited resources. The Systems Engineering
      Initiative for Patient Safety (SEIPS 2.0) model has the potential to guide a
      sustainable, site-tailored mobility intervention. Thus, the aim of the current
      study is to demonstrate an adaptation process guided by the SEIPS 2.0 model to
      articulate site-specific, culturally based interventions to improve in-hospital
      mobility among older adults. METHODS: Six consecutive phases addressed each of
      the model's elements in the research setting. Phase-1 aimed to determine a
      measurable outcome: steps/d, measured with accelerometers, associated with
      functional decline. Phase-2 included interviews with key persons in leadership
      positions in the hospital to explore organizational factors affecting in-hospital
      mobility. Phases-3 and 4 aimed to identify attitudes, knowledge, barriers, and
      current behaviors of medical staff (n = 116) and patients (n = 203) related to
      patient mobility. Phase-5 included four focus-groups with unit staff aimed at
      developing an action plan while adapting existing intervention strategies to site
      needs. Phase-6 relied on a steering committee that developed intervention
      adaptation and implementation plans. RESULTS: Nine hundred steps/d was defined as
      the intervention outcome. 40% of patients walked fewer than 900 steps/d
      regardless of capability. Assessing or promoting mobility did not exist as a
      separate task and thus was routinely overlooked. Several barriers to patients'
      mobility were identified, specifically limited knowledge of practical aspects of
      mobility. Consequently, staff adopted practical steps to address them. Nurses
      were designated to assess mobility, and nursing assistants to support mobility.
      Mobility was defined as a quality indicator to be documented in electronic
      medical records and closely supervised by hospital and unit management.
      Preliminary analyses of the "Walk FOR" protocol demonstrates its' ability to
      reduce barriers, to re-shape staff attitudes and knowledge, and to increase in
      hospital mobility of older adults. CONCLUSIONS: The SEIPS-2.0 model can serve as
      a useful guide for implementing a site-tailored comprehensive mobility
      intervention. This process, which relies on local resources, may promise
      sustainable practice change that may support early effective rehabilitation and
      recovery.

PMID- 29653508
TI  - Dynamic transcriptome landscape of Asian domestic honeybee (Apis cerana)
      embryonic development revealed by high-quality RNA sequencing.
AB  - BACKGROUND: Honeybee development consists of four stages: embryo, larva, pupa and
      adult. Embryogenesis, a key process of cell division and differentiation, takes 3
      days in honeybees. However, the embryonic transcriptome and the dynamic
      regulation of embryonic transcription are still largely uncharacterized in
      honeybees, especially in the Asian honeybee (Apis cerana). Here, we employed high
      quality RNA-seq to explore the transcriptome of Asian honeybee embryos at three
      ages, approximately 24, 48 and 72 h (referred to as Day1, Day2 and Day3,
      respectively). RESULTS: Nine embryo samples, three from each age, were collected
      for RNA-seq. According to the staging scheme of honeybee embryos and the
      morphological features we observed, our Day1, Day2 and Day3 embryos likely
      corresponded to the late stage four, stage eight and stage ten development
      stages, respectively. Hierarchical clustering and principal component analysis
      showed that same-age samples were grouped together, and the Day2 samples had a
      closer relationship with the Day3 samples than the Day1 samples. Finally, a total
      of 18,284 genes harboring 55,646 transcripts were detected in the A. cerana
      embryos, of which 44.5% consisted of the core transcriptome shared by all three
      ages of embryos. A total of 4088 upregulated and 3046 downregulated genes were
      identified among the three embryo ages, of which 2010, 3177 and 1528 genes were
      upregulated and 2088, 2294 and 303 genes were downregulated from Day1 to Day2,
      from Day1 to Day3 and from Day2 to Day3, respectively. The downregulated genes
      were mostly involved in cellular, biosynthetic and metabolic processes, gene
      expression and protein localization, and macromolecule modification; the
      upregulated genes mainly participated in cell development and differentiation,
      tissue, organ and system development, and morphogenesis. Interestingly, several
      biological processes related to the response to and detection of light stimuli
      were enriched in the first-day A. cerana embryogenesis but not in the Apis
      mellifera embryogenesis, which was valuable for further investigations.
      CONCLUSIONS: Our transcriptomic data substantially expand the number of known
      transcribed elements in the A. cerana genome and provide a high-quality view of
      the transcriptome dynamics of A. cerana embryonic development.

PMID- 29653509
TI  - Population sensitivity of acute flaccid paralysis and environmental surveillance
      for serotype 1 poliovirus in Pakistan: an observational study.
AB  - BACKGROUND: To support poliomyelitis eradication in Pakistan, environmental
      surveillance (ES) of wastewater has been expanded alongside surveillance for
      acute flaccid paralysis (AFP). ES is a relatively new method of surveillance, and
      the population sensitivity of detecting poliovirus within endemic settings
      requires estimation. METHODS: Data for wild serotype 1 poliovirus from AFP and ES
      from January 2011 to September 2015 from 14 districts in Pakistan were analysed
      using a multi-state model framework. This framework was used to estimate the
      sensitivity of poliovirus detection from each surveillance source and parameters
      such as the duration of infection within a community. RESULTS: The location and
      timing of poliomyelitis cases showed spatial and temporal variability. The
      sensitivity of AFP surveillance to detect serotype 1 poliovirus infection in a
      district and its neighbours per month was on average 30.0% (95% CI 24.8-35.8) and
      increased with the incidence of poliomyelitis cases. The average population
      sensitivity of a single environmental sample was 59.4% (95% CI 55.4-63.0), with
      significant variation in site-specific estimates (median varied from 33.3-79.2%).
      The combined population sensitivity of environmental and AFP surveillance in a
      given month was on average 98.1% (95% CI 97.2-98.7), assuming four samples per
      month for each site. CONCLUSIONS: ES can be a highly sensitive supplement to AFP
      surveillance in areas with converging sewage systems. As ES for poliovirus is
      expanded, it will be important to identify factors associated with variation in
      site sensitivity, leading to improved site selection and surveillance system
      performance.

PMID- 29653510
TI  - Factors affecting adherence to antiretroviral therapy among pregnant women in the
      Eastern Cape, South Africa.
AB  - BACKGROUND: Context-specific factors influence adherence to antiretroviral
      therapy (ART) among pregnant women living with HIV. Gaps exist in the
      understanding of the reasons for the variable outcomes of the prevention of
      mother-to-child transmission (PMTCT) programme at the health facility level in
      South Africa. This study examined adherence levels and reasons for non-adherence
      during pregnancy in a cohort of parturient women enrolled in the PMTCT programme
      in the Eastern Cape, South Africa. METHODS: This was a mixed-methods study
      involving 1709 parturient women in the Eastern Cape, South Africa. We conducted a
      multi-centre retrospective analysis of the mother-infant pair in the PMTCT
      electronic database in 2016. Semi-structured interviews of purposively selected
      parturient women with self-reported poor adherence (n = 177) were conducted to
      gain understanding of the main barriers to adherence. Binary logistic regression
      was used to determine the independent predictors of ART non-adherence. RESULTS: A
      high proportion (69.0%) of women reported perfect adherence. In the logistic
      regression analysis, after adjusting for confounding factors, marital status,
      cigarette smoking, alcohol use and non-disclosure to a family member were the
      independent predictors of non-adherence. Analysis of the qualitative data
      revealed that drug-related side-effects, being away from home, forgetfulness, non
      disclosure, stigma and work-related demand were among the main reasons for non
      adherence to ART. CONCLUSIONS: Non-adherence to the antiretroviral therapy among
      pregnant women in this setting is associated with lifestyle behaviours, HIV
      related stigma and ART side-effects. In order to eliminate mother-to-child
      transmission of HIV, clinicians need to screen for these factors at every
      antenatal clinic visit.

PMID- 29653511
TI  - Increased circulating chemerin in patients with advanced carotid stenosis.
AB  - BACKGROUND: Chemerin is an adipokine which plays a crucial role in
      atherosclerosis. Here, we examined whether circulating chemerin is enhanced in
      patients with advanced carotid stenosis. METHODS: Chemerin was quantified in 178
      patients prior to carotid end arterectomy (CEA) and in age- and gender-matched
      controls (n = 163). Chemerin levels were related to anthropometric, clinical and
      metabolic characteristics of the patients. RESULTS: Chemerin levels were higher
      in patients compared to controls (p <  0.001). Chemerin correlated to parameters
      associated with inflammation such as C-reactive protein (CRP, p <  0.001),
      leukocyte blood count (p <  0.001) and circulating TNF-alpha (p = 0.004) in the
      patients. Chemerin levels did not differ between asymptomatic (n = 93) and
      symptomatic patients who experienced an ischemic event within 6 months prior to
      CEA (n = 85). However, in the case of high-grade carotid stenosis (>= 90%),
      chemerin levels were higher in symptomatic (n = 44) compared to asymptomatic
      patients (n = 41, p = 0.014). Chemerin was increased in patients with (n = 50)
      compared to patients without (n = 128) coronary artery disease (CAD, p = 0.002).
      A high level of chemerin increases the risk for CAD in patients (p = 0.0013).
      CONCLUSIONS: Circulating chemerin is increased and correlates to inflammatory
      parameters in patients with advanced carotid stenosis.

PMID- 29653512
TI  - Transcriptome-wide identification of optimal reference genes for expression
      analysis of Pyropia yezoensis responses to abiotic stress.
AB  - BACKGROUND: Pyropia yezoensis, a marine red alga, is an ideal research model for
      studying the mechanisms of abiotic stress tolerance in intertidal seaweed. Real
      time quantitative polymerase chain reaction (RT-qPCR) is the most commonly used
      method to analyze gene expression levels. To accurately quantify gene expression,
      selection and validation of stable reference genes is required. RESULTS: We used
      transcriptome profiling data from different abiotic stress treatments to identify
      six genes with relatively stable expression levels: MAP, ATPase, CGS1, PPK, DPE2,
      and FHP. These six genes and three conventional reference genes, UBC, EF1-alpha,
      and eif4A, were chosen as candidates for optimal reference gene selection. Five
      common statistical approaches (geNorm, DeltaCt method, NormFinder, BestKeeper,
      and ReFinder) were used to identify the stability of each reference gene. Our
      results show that: MAP, UBC, and FHP are stably expressed in all analyzed
      conditions; CGS1 and UBC are stably expressed under conditions of dehydration
      stress; and MAP, UBC, and CGS1 are stably expressed under conditions of
      temperature stress. CONCLUSION: We have identified appropriate reference genes
      for RT-qPCR in P. yezoensis under different abiotic stress conditions which will
      facilitate studies of gene expression under these conditions.

PMID- 29653513
TI  - Serum BTP concentrations are not affected by hepatic dysfunction.
AB  - BACKGROUND: Beta Trace Protein (BTP) is a promising marker of glomerular
      filtration rate (GFR). Equations to estimate GFR using BTP have been proposed.
      Very little is known about BTP's production and metabolism. It has been
      hypothesized that the liver metabolizes certain BTP isoforms. As such, hepatic
      dysfunction may influence serum levels independently of GFR. This would impact on
      the accuracy and precision of GFR estimates using BTP. The purpose of this study
      was to assess the impact of cirrhosis on serum BTP concentrations. METHODS: BTP,
      cystatin C (cysC) and creatinine (Cr) were measured in 99 cirrhotic subjects and
      in matched controls. BTP/cysC and Cr/cysC ratios were compared between cases and
      controls. This was repeated after stratification by Child Pugh category.
      Comparisons of ratios between Child Pugh category A and combined B and C case
      subjects were also performed. RESULTS: There were no differences in BTP/cysC
      ratios between cases and controls for the entire cohort (0.80 vs 0.79) or for any
      of the Child Pugh categories (p > 0.10). There were significant differences
      between cases (1.09) and controls (0.73) for the BTP/Cr ratios (p < 0.001). The
      BTP/Cr ratio was higher in those with more advanced cirrhosis as compared to
      those with less severe cirrhosis (1.20 vs 1.03, p < 0.01). There were no
      differences in BTP/cysC ratios between those with less severe and more advanced
      cirrhosis (p = 0.25). CONCLUSIONS: This study suggests that hepatic dysfunction
      does not influence serum BTP levels and argues against a significant role for the
      liver in BTP metabolism. Confirmation in a larger group of patients with advanced
      cirrhosis is required.

PMID- 29653514
TI  - Genetic evidence suggests that GIS functions downstream of TCL1 to regulate
      trichome formation in Arabidopsis.
AB  - BACKGROUND: Trichome formation in Arabidopsis is regulated by a MBW complex
      formed by MYB, bHLH and WD40 transcriptional factors, which can activate GLABRA2
      (GL2) and the R3 MYB transcription factor genes. GL2 promotes trichome formation,
      whereas R3 MYBs are able to block the formation of the MBW complex. It has been
      reported that the C2H2 transcription factor GIS (GLABROUS INFLORESCENCE STEMS)
      functions upstream of the MBW activator complex to regulate trichome formation,
      and that the expression of TCL1 is not regulated by the MBW complex. However, gis
      and the R3 MYB gene mutant tcl1 (trichomeless 1) have opposite inflorescence
      trichome phenotypes, but their relationship in regulating trichome formation
      remained unknown. RESULTS: By generating and characterization of the gis tcl1
      double mutant, we found that trichome formation in the gis tcl1double and the
      tcl1 single mutants were largely indistinguishable, but the trichome formation in
      the 35S:TCL1/gis transgenic plant was similar to that in the gis mutant. By using
      quantitative RT-PCR analysis, we showed that expression level of GIS was
      increased in the triple mutant tcl1 try cpc, but the expression level of TCL1 was
      not affected in the gis mutant. On the other hand, trichome morphology in both
      gis tcl1 and 35S:TCL1/gis plants was similar to that in the gis mutant.
      CONCLUSIONS: In summary, our results indicate that GIS may work downstream of
      TCL1 to regulate trichome formation, and GIS has a dominant role in controlling
      trichome morphology.

PMID- 29653515
TI  - Relationship between muscle strength and fall episodes among the elderly: the
      Yilan study, Taiwan.
AB  - BACKGROUND: Fall episodes are not unusual among community residents, especially
      the elderly, and lower muscle strength is an important issue to address in order
      to prevent falls. METHODS: A community health survey was conducted in a suburban
      area of Taiwan, and 1067 older adults were selected for enrollment in the present
      study. All the enrolled subjects had been visited at their homes; the subjects'
      strength of both hands and muscle mass of both legs were measured and well
      established questionnaires were finished by certificated paramedic staffs.
      RESULTS: The incidence of fall episodes in the previous 1 year in the Yilan
      elderly population was 15.1%, and the female predominance was significant. A
      significantly higher prevalence of cataracts was found in group who experienced a
      fall in the past year (64% vs. 54.9% in the non-fall group). Mild or more severe
      dementia was much more prevalent in the group who experienced a recent fall
      (33.8% vs. 25.7% in the non-fall group). The strength of both hands tested as the
      physical function was 17.6 +/- 8.0 kg in the recent fall group, significantly
      weaker than that in the non-fall group (20.7 +/- 8.7 kg). Multivariate regression
      analysis revealed a greater weekly exercise duration and greater strength of both
      hands reduced the occurrence of falls among the whole and the female population.
      The standardized effect sizes of hand grip strength between both groups, not
      trivial, were 0.29 and 0.37 for the total population and the female subpopulation
      respectively. CONCLUSIONS: Less weekly exercise duration and weaker muscle
      strength were f ound to be independent risk factors of fall episode(s) in an
      elderly Taiwanese population, especially in the female sub-population. Muscle
      strength, measured by average of both hands grip strength, was the most
      significantly factor of one-year fall episode(s) accessed retrospectively.

PMID- 29653516
TI  - A rare case of skin blistering and esophageal stenosis in the course of
      epidermolysis bullosa - case report and literature review.
AB  - BACKGROUND: Epidermolysis bullosa (EB) constitutes a heterogenous group of rare
      multisystem genetically transmitted disorders comprising several blistering muco
      cutaneous diseases with a monogenic basis and either autosomal dominant or
      autosomal recessive mode of inheritance. EB manifestation is not only limited to
      the skin. Systemic signs might involve the nose, ear, eye, genitourinary tract
      and upper gastrointestinal tract. The presence of particular symptoms is directly
      determined by a type of altered skin protein. Gastrointestinal manifestation of
      EB is most commonly reflected by esophageal stenosis due to recurrent esophageal
      blistering, followed by consequent scarring. CASE PRESENTATION: Here we present a
      case of a man with dystrophic EB and dysphagia, skin blistering, joints
      contractures and missing nails. To our knowledge, the presented man is the oldest
      one diagnosed with EB living in Poland. CONCLUSIONS: Management of an esophageal
      stricture in such circumstances is based on endoscopic dilatation. However, in
      most severe cases, placement of a gastrostomy tube is required. Despite great
      advances in medicine, a targeted therapy in the course of EB has not been
      established yet.

PMID- 29653517
TI  - Advances in anesthesia technology are improving patient care, but many challenges
      remain.
AB  - Although significant advances in clinical monitoring technology and clinical
      practice development have taken place in the last several decades, in this
      editorial we argue that much more still needs to be done. We begin by identifying
      many of the improvements in perioperative technology that have become available
      in recent years; these include electroencephalographic depth of anesthesia
      monitoring, bedside ultrasonography, advanced neuromuscular transmission
      monitoring systems, and other developments. We then discuss some of the
      perioperative technical challenges that remain to be satisfactorily addressed,
      such as products that incorporate poor software design or offer a confusing user
      interface. Finally we suggest that the journal support initiatives to help remedy
      this problem by publishing reports on the evaluation of medical equipment as a
      means to restore the link between clinical research and clinical end-users.

PMID- 29653518
TI  - Genexpi: a toolset for identifying regulons and validating gene regulatory
      networks using time-course expression data.
AB  - BACKGROUND: Identifying regulons of sigma factors is a vital subtask of gene
      network inference. Integrating multiple sources of data is essential for correct
      identification of regulons and complete gene regulatory networks. Time series of
      expression data measured with microarrays or RNA-seq combined with static binding
      experiments (e.g., ChIP-seq) or literature mining may be used for inference of
      sigma factor regulatory networks. RESULTS: We introduce Genexpi: a tool to
      identify sigma factors by combining candidates obtained from ChIP experiments or
      literature mining with time-course gene expression data. While Genexpi can be
      used to infer other types of regulatory interactions, it was designed and
      validated on real biological data from bacterial regulons. In this paper, we put
      primary focus on CyGenexpi: a plugin integrating Genexpi with the Cytoscape
      software for ease of use. As a part of this effort, a plugin for handling time
      series data in Cytoscape called CyDataseries has been developed and made
      available. Genexpi is also available as a standalone command line tool and an R
      package. CONCLUSIONS: Genexpi is a useful part of gene network inference toolbox.
      It provides meaningful information about the composition of regulons and delivers
      biologically interpretable results.

PMID- 29653519
TI  - RS3PE syndrome developing during the course of probable toxic shock syndrome: a
      case report.
AB  - BACKGROUND: Remitting seronegative symmetrical synovitis with pitting edema
      (RS3PE) is a rare syndrome characterized by "remitting," "seronegative" (namely
      rheumatoid factor-negative), and "symmetrical" synovitis with pitting edema on
      the dorsum of the hands and feet. Recently, there have been reports that serum
      vascular endothelial growth factor (VEGF) is elevated in this condition. CASE
      PRESENTATION: An 85-year-old man visited our department with a rash that had
      appeared 2 days earlier and a fever that had developed on the day of his visit.
      Based on clinical findings of fever, erythema exudativum multiforme, transitory
      hypotension, conjunctiva hyperemia, elevated creatine kinase, and desquamation,
      we suspected toxic shock syndrome (TSS). Therefore, we started treatment with
      vancomycin (1 g/day) and clindamycin (600 mg/day), after which his fever rapidly
      remitted. However, pitting edema on the dorsum of his hands and feet appeared on
      day 7, and the patient also had painful wrist and ankle joints. Additional tests
      were negative for rheumatoid factor, and anti-cyclic citrullinated protein
      antibodies were < 0.2 U/mL. Further, serum matrix metalloproteinase-3 (199.6
      ng/mL; reference value <=123.8 ng/mL) and serum VEGF (191 pg/mL; reference value
      <=38.3 pg/mL) levels were elevated, and human leukocyte antigen-A2 was detected.
      The patient was thus diagnosed with RS3PE syndrome, for which he satisfied all
      four diagnostic criteria: 1) pitting edema in the limbs, 2) acute onset, 3) age
      >= 50 years, and 4) rheumatoid factor negativity. He was treated with oral
      prednisolone, resulting in the normalization of his serum VEGF level to 34.5
      pg/mL 1 month after starting treatment. It is currently 1 year since disease
      onset, and although the patient has stopped taking prednisolone, there has been
      no recurrence of RS3PE syndrome. CONCLUSIONS: To the best of our knowledge, this
      is the first reported case of a patient developing RS3PE syndrome during the
      clinical course of TSS. We propose that the onset mechanism involved an increase
      in blood VEGF due to TSS, which induced RS3PE syndrome. As serum VEGF becomes
      elevated with both severe infections associated with shock and RS3PE syndrome,
      awareness that these conditions can occur concurrently is essential.

PMID- 29653520
TI  - A modified sequence capture approach allowing standard and methylation analyses
      of the same enriched genomic DNA sample.
AB  - BACKGROUND: Bread wheat has a large complex genome that makes whole genome
      resequencing costly. Therefore, genome complexity reduction techniques such as
      sequence capture make re-sequencing cost effective. With a high-quality draft
      wheat genome now available it is possible to design capture probe sets and to use
      them to accurately genotype and anchor SNPs to the genome. Furthermore, in
      addition to genetic variation, epigenetic variation provides a source of natural
      variation contributing to changes in gene expression and phenotype that can be
      profiled at the base pair level using sequence capture coupled with bisulphite
      treatment. Here, we present a new 12 Mbp wheat capture probe set, that allows
      both the profiling of genotype and methylation from the same DNA sample.
      Furthermore, we present a method, based on Agilent SureSelect Methyl-Seq, that
      will use a single capture assay as a starting point to allow both DNA sequencing
      and methyl-seq. RESULTS: Our method uses a single capture assay that is
      sequentially split and used for both DNA sequencing and methyl-seq. The resultant
      genotype and epi-type data is highly comparable in terms of coverage and
      SNP/methylation site identification to that generated from separate captures for
      DNA sequencing and methyl-seq. Furthermore, by defining SNP frequencies in a
      diverse landrace from the Watkins collection we highlight the importance of
      having genotype data to prevent false positive methylation calls. Finally, we
      present the design of a new 12 Mbp wheat capture and demonstrate its successful
      application to re-sequence wheat. CONCLUSIONS: We present a cost-effective method
      for performing both DNA sequencing and methyl-seq from a single capture reaction
      thus reducing reagent costs, sample preparation time and DNA requirements for
      these complementary analyses.

PMID- 29653521
TI  - Risk factors for hepatitis E virus seropositivity in Dutch blood donors.
AB  - BACKGROUND: A marked increase of hepatitis E cases has recently been observed in
      the Netherlands. Causes of the (re-)emergence of hepatitis E virus (HEV) and
      exact sources and routes of transmission of HEV infection are currently unknown.
      We aimed to identify risk factors for HEV seropositivity. METHODS: Using the
      Wantai EIA, 2100 plasma samples of blood donors from all over the Netherlands
      aged 18-70 years were tested for anti-HEV IgG antibodies. A questionnaire on
      socio-demographic characteristics, health, and potential risk factors for HEV
      exposure was sent to these participants. RESULTS: The overall IgG-seroprevalence
      was 31% (648/2100) and increased with age. Several food products were
      independently associated with IgG-seropositivity in a multivariate analysis
      adjusting for age and gender among 1562 participants who completed the
      questionnaire: traditional Dutch dry raw sausages called "cervelaat", "fijnkost",
      "salami" and "salametti" which are generally made from raw pork and beef (aOR
      1.5; 95%CI 1.2-1.9), frequent consumption of bovine steak (aOR 1.3; 95%CI 1.0
      1.7), and frequent consumption of smoked beef (aOR 1.3 95%CI 1.0-1.7). Although
      not frequently reported, contact with contaminated water was also a risk factor
      for seropositivity (aOR 2.5; 95%CI 1.5-4.4). Lower seroprevalence was associated
      with eating raspberries, going out for dinner, and contact with wild animals and
      dogs. CONCLUSION: Several pork food products, mainly dry raw sausages, and
      contact with contaminated water were associated with past HEV infection in the
      Netherlands. Further investigation is needed into the prevalence and infectivity
      of HEV in these risk factor food products, as well as investigation of the
      production methods and possible origin of HEV-contamination within these
      sausages, e.g. very small amounts of pork liver, pig-derived blood products as
      food additive, or the pork muscle tissue.

PMID- 29653522
TI  - Correction to: A pattern learning-based method for temporal expression extraction
      and normalization from multi-lingual heterogeneous clinical texts.
AB  - After publication of the original article [1] it was noted that the captions
      relating to Figs. 2 and 3 had been interchanged.

PMID- 29653523
TI  - A video-based transdiagnostic REBT universal prevention program for internalizing
      problems in adolescents: study protocol of a cluster randomized controlled trial.
AB  - BACKGROUND: Internalizing problems are the most prevalent mental health problems
      in adolescents. Transdiagnostic programs are promising manners to treat multiple
      problems within the same protocol, however, there is limited research regarding
      the efficacy of such programs delivered as universal prevention programs in
      school settings. Therefore, the present study aims to investigate the efficacy of
      a video-based transdiagnostic rational emotive behavioral therapy (REBT)
      universal prevention program, for internalizing problems. The second objective of
      the present paper will be to investigate the subsequent mechanisms of change,
      namely maladaptive cognitions. METHODS: A two-arm parallel randomized controlled
      trial will be conducted, with two groups: a video-based transdiagnostic REBT
      universal prevention program and a wait list control. Power analysis indicated
      that the study will involve 338 participants. Adolescents with ages between 12
      and 17 years old, from several middle schools and high schools, will be invited
      to participate. Assessments will be conducted at four time points: baseline (T1),
      post-intervention (T2), 3 months follow-up (T3) and 12 months follow-up (T4).
      Intent-to-treat analysis will be used in order to investigate significant
      differences between the two groups in both primary and secondary outcomes.
      DISCUSSION: This is the first randomized controlled trial that aims to
      investigate the efficacy and mechanisms of change of a video-based
      transdiagnostic REBT universal prevention program, delivered in a school context.
      The present study has important implications for developing efficient prevention
      programs, interactive, that will aim to target within the same protocol both
      anxiety and depressive symptoms. TRIAL REGISTRATION: ClinicalTrials.gov:
      NCT02756507 . Registered on 25 April 2016.

PMID- 29653524
TI  - Smokers' unprompted comments on cigarette additives during conversations about
      the genetic basis for nicotine addiction: a focus group study.
AB  - BACKGROUND: Research designed to elicit smokers' cognitive and affective
      reactions to information about chemicals that tobacco companies add to cigarettes
      ("additives") found that knowledge is limited. However, little is known about
      smokers' unprompted thoughts and feelings about additives. Such information could
      be used to shape future communication efforts. We explored the content and
      possible functions of spontaneous statements about cigarette additives made by
      smokers during a study examining reactions to learning about the genetic link to
      nicotine addiction. METHODS: Adult smokers (N = 84) were recruited from a medium
      sized Midwestern city. Focus groups (N = 13) were conducted between April
      September 2012. Data were analyzed by 2 coders using thematic analysis. RESULTS:
      Comments about cigarette additives arose without prompting by the focus group
      moderator. Three main themes were identified: (1) discussing additives helped
      participants navigate the conceptual link between smoking and genetics, (2)
      additives were discussed as an alternative mechanism for addiction to cigarettes,
      and (3) additives provided an alternative mechanism by which cigarette smoking
      exacerbates physical harm. Notably, discussion of additives contained a pervasive
      tone of mistrust illustrated by words like "they" and "them," by statements of
      uncertainty such as "you don't know what they're putting into cigarettes," and by
      negative affective verbalizations such as "nasty" and "disgusting". CONCLUSIONS:
      Participants had distinct beliefs about cigarette additives, each of which seemed
      to serve a purpose. Although mistrust may complicate communication about the
      health risks of tobacco use, health communication experts could use smokers'
      existing beliefs and feelings to better design more effective anti-smoking
      messages.

PMID- 29653525
TI  - Understanding the risk and protective factors associated with obesity amongst
      Libyan adults - a qualitative study.
AB  - BACKGROUND: There are a range of multifaceted behavioural and societal factors
      that combine to contribute to the causes of obesity. However, it is not yet known
      how particularly countries' cultural norms are contributing to the global obesity
      epidemic. Despite obesity reaching epidemic proportions in Libya, since the
      discovery of oil in 1959, there is a lack of information about obesity in Libyan
      adults. This study sought to explore the views of key informants about the risk
      and protective factors associated with obesity among Libyan men and women.
      METHODS: A series of qualitative semi-structured interviews were conducted with
      Libyan healthcare professionals and community leaders. RESULTS: Eleven main
      themes (risk and protective factors) were identified, specifically: socio
      demographic and biological factors, socioeconomic status, unhealthy eating
      behaviours, knowledge about obesity, social-cultural influences, Libya's
      healthcare facilities, physical activity and the effect of the neighbourhood
      environment, sedentary behaviour, Libyan food-subsidy policy, and suggestions for
      preventing and controlling obesity. CONCLUSIONS: Key recommendations are that an
      electronic health information system needs to be implemented and awareness about
      obesity and its causes and consequences needs to be raised among the public in
      order to dispel the many myths and misconceptions held by Libyans about obesity.
      The current political instability within Libya is contributing to a less-active
      lifestyle for the population due to security concerns and the impact of curfews.
      Our findings have implications for Libyan health policy and highlight the urgent
      need for action towards mitigating against the obesity epidemic in Libya.

PMID- 29653526
TI  - Clostridium difficile stool shedding in infants hospitalized in two neonatal
      intensive care units is lower than previous point prevalence estimates using
      molecular diagnostic methods.
AB  - BACKGROUND: The point prevalence of Clostridium difficile stool shedding in
      hospitalized infants from two neonatal intensive care units (NICUs) was examined
      utilizing standard clinical testing compared with duplex PCR to identify
      toxigenic and non-toxigenic C. difficile strains. METHODS: All infants from the
      two NICUs affiliated with a single academic medical center were eligible for
      inclusion. Stool collection was blinded to patient characteristics and occurred
      during a one week period at each NICU and repeated with a second weeklong
      collection 6 months later to increase sample size. Stools were tested for C.
      difficile using EIA (GDH/toxin A/B) with samples testing +/+ or +/- subsequently
      evaluated by Loop-Mediated Isothermal Amplification (LAMP) and by duplex PCR
      amplification of tcdB and tpi (housekeeping) genes. Cytotoxicity assays were
      performed on all samples positive for C. difficile by any modality. RESULTS:
      Eighty-four stools were collected from unique infants for evaluation. EIA results
      showed 6+/+ [7.1%], 7 +/- [8.3%], and 71 -/- [84.5%] samples. All 6 EIA +/+ were
      confirmed as toxigenic C. difficile by LAMP; 6/7 EIA +/- were negative by LAMP
      with one identified as invalid. Duplex PCR concurred with LAMP in all 6 stools
      positive for toxigenic C. difficile. PCR identified 2 EIA -/- stools positive for
      tpi, indicating shedding of non-toxigenic C. difficile. Cytotoxicity assay was
      positive in 4/6 duplex PCR positive samples and negative for all stools that were
      EIA +/- but negative by molecular testing. CONCLUSIONS: C. difficile blinded
      point prevalence in infants from two NICUs was 7.1% by molecular methods; and
      lower than expected based on historical incidence estimates. In house duplex PCR
      had excellent concordance with clinically available LAMP and EIA tests, and added
      detection of non-toxigenic C. difficile strain shedding. Evolving NICU care
      practices may be influencing the composition of infant gut microbiota and
      reducing the point prevalence of C. difficile shedding in NICU patient stools.

PMID- 29653527
TI  - Preventing tobacco in vocational high schools: study protocol for a randomized
      controlled trial of P2P, a peer to peer and theory planned behavior-based
      program.
AB  - BACKGROUND: In France, the issue of youth smoking remains a major challenge for
      public health. School failure, socio-economic and socio-cultural backgrounds
      influence the initiation and maintenance of smoking behavior in adolescents.
      Vocational students are at particularly high risk of using psychoactive
      substances, including tobacco. One of the most important factors is the
      environment, whether family, friends or peers. Therefore, peer education has a
      positive potential to change smoking behavior of adolescents. It has also been
      demonstrated that the Theory of Planned Behavior (TPB) has yielded the best
      prediction of intentions and behavior, in several health domains, including on
      tobacco. However, it is usually confined to the measurement of processes by which
      interventions change behavior, rather than to the development of these
      interventions. The objective of this paper is to describe the protocol for a
      randomized controlled trial of a peer intervention based on the TPB on a highly
      exposed young population. METHODS/DESIGNS: This is a cluster randomized
      controlled trial comparing an intervention group to a control group, randomized
      into clusters (professional schools and classes) and stratified in three
      departments (Herault, Aude and Gard) in the Languedoc-Roussillon region. The
      primary issue is the prevalence of daily smoking at 24 months, defined by a daily
      tobacco use of at least 1 cigarette, validated by CO levels in exhaled air. The
      primary hypothesis is that intervention will lead to decrease the daily smoking
      prevalence of 10% between the intervention group and the control group during a 2
      year follow-up. DISCUSSION: The results from this trial will provide evidence on
      the effectiveness of an innovative peer-to-peer intervention based on the TPB.
      TRIAL REGISTRATION: ISRCTN: 37336035 , Retrospectively registered 11/12/2015.

PMID- 29653528
TI  - Physical activity, sedentary time and sleep duration: associations with body
      composition in 10-12-year-old Estonian schoolchildren.
AB  - BACKGROUND: Physical activity, sedentary time, and sleep duration have been
      associated with body composition among children. The purpose of the present study
      was to assess the associations of objectively determined daily physical activity,
      sedentary time, sleep duration and body composition indices in 10-12-year-old
      children. METHODS: Two hundred and eleven schoolchildren (96 boys and 115 girls)
      aged 10.9 +/- 0.7 years participated in this study. Objective physical activity
      intensity and sedentary levels were measured for seven days by accelerometry.
      Sleep duration was self-reported. Percentage of body fat, waist-to-height ratio
      and fat free mass were calculated from measured anthropometric parameters.
      Multiple linear regression models were used to examine the associations between
      sleep duration, moderate-to-vigorous physical activity (MVPA), vigorous physical
      activity (VPA) level and body composition indices. RESULTS: Boys exceeded girls
      (p < 0.05) in time spent in MVPA and VPA levels. Only 4.3% of the children met
      the current daily recommendation of at least 60 min MVPA per day. Sleep duration,
      MVPA and VPA had a negative association with percentage of body fat and waist-to
      height ratio. Vigorous physical activity had a positive association with fat-free
      mass. Sedentary time had a positive association with percentage of body fat and
      negative association with fat-free mass. CONCLUSIONS: The present study suggests
      that both sleep duration and MVPA are associated with body composition
      parameters. Higher levels of MVPA are associated with lower percentage of body
      fat and waist-to-height ratio regardless of sleep duration. Sedentary time is
      associated with higher values of percentage of body fat and lower fat-free mass
      independently of sleep duration.

PMID- 29653529
TI  - Scale-out of a community-based behavioral intervention for childhood obesity:
      pilot implementation evaluation.
AB  - BACKGROUND: Expanding the use of evidence-based behavioral interventions in
      community settings has met with limited success in various health outcomes as
      fidelity and dose of clinical interventions are often diluted when translated to
      communities. We conducted a pilot implementation study to examine adoption of the
      rigorously evaluated Healthier Families Program by Parks and Recreation centers
      in 3 cities across the country (MI, GA, NV) with diverse socio-cultural
      environments. METHODS: Using the RE-AIM framework, we evaluated the program both
      quantitatively (pre/post surveys of health behavior change; attendance &
      fidelity) and qualitatively (interviews with Parks and Recreation staff and
      participants following the program). RESULTS: The 3 partner sites recruited a
      total of 26 parent-child pairs. REACH: Among the 24 participants who completed
      pre/post surveys, 62.5% were 25-34 years old, and average child age was 3.6 (SD
      0.7) years. The distribution of self-reported race/ethnicity was 54% non-Hispanic
      White, 38% non-Hispanic Black, and 8% Latino. EFFECTIVENESS: Qualitative
      interviews with participants demonstrated increased use of the built environment
      for physical activity and continued use of key strategies for health behavior
      change. ADOPTION: Three of five (60%) collaborating sites proceeded with
      implementation of the program. IMPLEMENTATION: The average attendance for the 12
      week program was 7.6 (SD 3.9) sessions, with 71% attending > 50% of sessions.
      Average fidelity for the 12 weekly sessions was 25.2 (SD 1.2; possible range 9
      27). MAINTENANCE: All 3 partner sites continued offering the program after grant
      funding was complete. CONCLUSIONS: This pilot is among the first attempts to
      scale-out an evidence-based childhood obesity intervention in community Parks and
      Recreation centers. While this pilot was not intended to confirm the efficacy of
      the original trial on Body Mass Index (BMI) reduction, the effective and
      sustained behavior change among a geographically and ethnically diverse
      population with high attendance and fidelity demonstrates an effective approach
      on which to base future large-scale implementation efforts to reduce childhood
      obesity in community settings.

PMID- 29653530
TI  - Predictors of physicians' stress related to information systems: a nine-year
      follow-up survey study.
AB  - BACKGROUND: Among the important stress factors for physicians nowadays are poorly
      functioning, time consuming and inadequate information systems. The present study
      examined the predictors of physicians' stress related to information systems
      (SRIS) among Finnish physicians. The examined predictors were cognitive workload,
      staffing problems, time pressure, problems in teamwork and job satisfaction,
      adjusted for baseline levels of SRIS, age, gender and employment sector. METHODS:
      The study has a follow-up design with two survey data collection waves, one in
      2006 and one in 2015, based on a random sample of Finnish physicians was used.
      The present study used a sample that included 1109 physicians (61.9% women; mean
      age in 2015 was 54.5; range 34-72) who provided data on the SRIS in both waves.
      The effects of a) predictor variable levels in 2006 on SRIS in 2015 and b) the
      change in the predictor variables from 2006 to 2015 on SRIS in 2015 were analysed
      with linear regression analyses. RESULTS: Regression analyses showed that the
      higher level of cognitive workload in 2006 significantly predicted higher level
      of SRIS in 2015 (beta = 0.08). The reciprocity of this association was tested
      with cross-lagged structural equation model analyses which showed that the
      direction of the association was from cognitive workload to SRIS, not from SRIS
      to cognitive workload. Moreover, increases in time pressure (beta = 0.16) and
      problems in teamwork (beta = 0.10) were associated with higher levels of SRIS in
      2015, whereas job satisfaction increase was associated with lower SRIS (beta = -
      0.06). CONCLUSIONS: According to our results, physicians' cognitive workload may
      have long-lasting negative ramifications in regard to how stressful physicians
      experience their health information systems to be. Thus, organisations should pay
      attention to physicians workload if they wish physicians to master all the
      systems they need to use. It is also important to provide physicians with enough
      time and collegial support in their system-related problems, and in learning new
      systems and system updates.

PMID- 29653531
TI  - Improving social accountability processes in the health sector in sub-Saharan
      Africa: a systematic review.
AB  - BACKGROUND: Social accountability is a participatory process in which citizens
      are engaged to hold politicians, policy makers and public officials accountable
      for the services that they provide. In the Fifteenth Ordinary Session of the
      Assembly of the African Union, African leaders recognized the need for strong,
      decentralized health programs with linkages to civil society and private sector
      entities, full community participation in program design and implementation, and
      adaptive approaches to local political, socio-cultural and administrative
      environments. Despite the increasing use of social accountability, there is
      limited evidence on how it has been used in the health sector. The objective of
      this systematic review was to identify the conditions that facilitate effective
      social accountability in sub-Saharan Africa. METHODS: Electronic databases
      (MEDLINE, PsycINFO, Sociological Abstracts, Social Sciences Abstracts) were
      searched for relevant articles published between 2000 and August 2017. Studies
      were eligible for inclusion if they were peer-reviewed English language
      publications describing a social accountability intervention in sub-Saharan
      Africa. Qualitative and quantitative study designs were eligible. RESULTS:
      Fourteen relevant studies were included in the review. The findings indicate that
      effective social accountability interventions involve leveraging partnerships and
      building coalitions; being context-appropriate; integrating data and information
      collection and analysis; clearly defined roles, standards, and responsibilities
      of leaders; and meaningful citizen engagement. Health system barriers,
      corruption, fear of reprisal, and limited funding appear to be major challenges
      to effective social accountability interventions. CONCLUSION: Although global
      accountability standards play an important guiding role, the successful
      implementation of global health initiatives depend on national contexts.

PMID- 29653533
TI  - Comparing private and public transport access to diabetic health services across
      inner, middle, and outer suburbs of Melbourne, Australia.
AB  - BACKGROUND: Melbourne, Australia is experiencing rapid population growth, with
      much of this occurring in metropolitan outer suburban areas, also known as urban
      growth areas. Currently little is known about differences in travel times when
      using private and public transport to access primary and secondary services
      across Melbourne's urban growth areas. Plan Melbourne Refresh, a recent strategic
      land use document has called for a 20 min city, which is where essential services
      including primary health care, can be accessed within a 20 min journey. Type 2
      diabetes mellitus (T2DM) is a major chronic condition in Australia, with some of
      Melbourne's growth areas having some of the highest prevalence across Australia.
      This study explores travel times to diabetic health care services for populations
      residing in inner, middle and outer suburbs of metropolitan Melbourne. METHOD:
      Geographic information systems (GIS) software were used to map the location of
      selected diabetic primary and secondary health care service providers across
      metropolitan inner, middle, outer established, outer urban growth and outer
      fringe areas of Melbourne. An origin-destination matrix was used to estimate
      travel distances from point of origin (using a total of approximately 50,000
      synthetic residential addresses) to the closest type of each diabetic health care
      service provider (destinations) across Melbourne. ArcGIS was used to estimate
      travel times for private transport and public transport; comparisons were made by
      area. RESULTS: Our study indicated increased travel times to diabetic health
      services for people living in Melbourne's outer growth and outer fringe areas
      compared with the rest of Melbourne (inner, middle and outer established).
      Compared with those living in inner city areas, the median time spent travelling
      to diabetic services was between 2.46 and 23.24 min (private motor vehicle) and
      12.01 and 43.15 min (public transport) longer for those living in outer suburban
      areas. Irrespective of travel mode used, results indicate that those living in
      inner and middle suburbs of Melbourne have shorter travel times to access
      diabetic health services, compared with those living in outer areas of Melbourne.
      Private motor vehicle travel times were approximately 4 to 5 times faster than
      public transport modes to access diabetic health services in all areas.
      CONCLUSION: Those living in new urban growth communities spend considerably more
      time travelling to access diabetic health services - particularly specialists -
      than those living in established areas across Melbourne.

PMID- 29653532
TI  - An internet-based intervention for people with psychosis (EviBaS): study protocol
      for a randomized controlled trial.
AB  - BACKGROUND: Evidence shows that internet-based self-help interventions are
      effective in reducing symptoms for a wide range of mental disorders. To date,
      online interventions treating psychotic disorders have been scarce, even though
      psychosis is among the most burdensome disorders worldwide. Furthermore, the
      implementation of cognitive-behavioral therapy (CBT) for psychosis in routine
      health care is challenging. Internet-based interventions could narrow this
      treatment gap. Thus, a comprehensive CBT-based online self-help intervention for
      people with psychosis has been developed. The aim of this study is the evaluation
      of the feasibility and efficacy of the intervention compared with a waiting list
      control group. METHODS: The intervention includes modules on delusion, voice
      hearing, social competence, mindfulness, and seven other domains. Participants
      are guided through the program by a personal moderator. Usage can be amended by
      an optional smartphone app. In this randomized controlled trial, participants are
      allocated to a waiting list or an intervention of eight weeks. Change in positive
      psychotic symptoms of both groups will be compared (primary outcome) and
      predictors of treatment effects will be assessed. DISCUSSION: To our knowledge,
      this project is one of the first large-scale investigations of an internet-based
      intervention for people with psychosis. It may thus be a further step to broaden
      treatment options for people suffering from this disorder. TRIAL REGISTRATION:
      NCT02974400 (clinicaltrials.gov), date of registration: November 28th 2016.

PMID- 29653534
TI  - A phylogenomic framework and timescale for comparative studies of tunicates.
AB  - BACKGROUND: Tunicates are the closest relatives of vertebrates and are widely
      used as models to study the evolutionary developmental biology of chordates.
      Their phylogeny, however, remains poorly understood, and to date, only the 18S
      rRNA nuclear gene and mitogenomes have been used to delineate the major groups of
      tunicates. To resolve their evolutionary relationships and provide a first
      estimate of their divergence times, we used a transcriptomic approach to build a
      phylogenomic dataset including all major tunicate lineages, consisting of 258
      evolutionarily conserved orthologous genes from representative species. RESULTS:
      Phylogenetic analyses using site-heterogeneous CAT mixture models of amino acid
      sequence evolution resulted in a strongly supported tree topology resolving the
      relationships among four major tunicate clades: (1) Appendicularia, (2) Thaliacea
      + Phlebobranchia + Aplousobranchia, (3) Molgulidae, and (4) Styelidae + Pyuridae.
      Notably, the morphologically derived Thaliacea are confirmed as the sister group
      of the clade uniting Phlebobranchia + Aplousobranchia within which the precise
      position of the model ascidian genus Ciona remains uncertain. Relaxed molecular
      clock analyses accommodating the accelerated evolutionary rate of tunicates
      reveal ancient diversification (~ 450-350 million years ago) among the major
      groups and allow one to compare their evolutionary age with respect to the major
      vertebrate model lineages. CONCLUSIONS: Our study represents the most
      comprehensive phylogenomic dataset for the main tunicate lineages. It offers a
      reference phylogenetic framework and first tentative timescale for tunicates,
      allowing a direct comparison with vertebrate model species in comparative
      genomics and evolutionary developmental biology studies.

PMID- 29653535
TI  - Efficacy of shared decision-making on treatment adherence of patients with
      bipolar disorder: a cluster randomized trial (ShareD-BD).
AB  - BACKGROUND: Shared decision-making (SDM) is a model of interaction between
      doctors and patients in which both actors contribute to the medical decision
      making process. SDM has raised great interest in mental healthcare over the last
      decade, as it is considered a fundamental part of patient-centered care. However,
      there is no research evaluating the efficacy of SDM compared to usual care (CAU),
      as it relates to quality of care and more specifically treatment adherence, in
      bipolar disorder (BD). METHODS/DESIGN: This is a 12-month multi-centre, cluster
      randomized controlled trial comparing the efficacy of SDM to CAU. Adult BD
      patients (n = 300) will be eligible after stabilization for at least 4 weeks
      following an acute mood episode. The intervention will consist of applying the
      standardized SDM process as developed by the Ottawa Hospital Research Institute
      in order to choose the maintenance treatment of BD. A multidisciplinary team
      developed a decision aid "choose my long-term treatment with my doctor" for BD
      patients to clarify possible therapeutic options. Primary outcome will assess the
      patient's level of adherence (based on hetero-evaluation) of ongoing treatment at
      12 months. Secondary outcomes will assess the difference between the 2 groups of
      patients in terms of adherence to maintenance drug therapy based on other
      measures (self-assessment scale and plasma levels of mood stabilizers).
      Additionally, other dimensions will be assessed: decisional conflict,
      satisfaction with care and involvement in decision making, beliefs about
      treatment, therapeutic relationship, knowledge about information for medical
      decision and clinical outcomes (depression, mania, functioning and quality of
      life). The primary endpoint will be analysed without adjustment by comparison of
      adherence scores between the two groups using Student t-tests or Mann-Whitney
      tests according to the variable distribution. A set of secondary analyses will be
      adjusted for covariates of clinical interest using generalized linear mixed
      regression models. DISCUSSION: This will be the first study evaluating the effect
      of an SDM intervention on patient adherence in BD. This is also an innovative
      protocol because it proposes the development of an evidence-based tool that
      should help patients and clinicians to initiate discussions regarding the use of
      BD treatment. TRIAL REGISTRATION: The study has been registered with
      ClinicalTrials.gov as NCT03245593 .

PMID- 29653536
TI  - Acceptability of HIV self-sampling kits (TINY vial) among people of black African
      ethnicity in the UK: a qualitative study.
AB  - BACKGROUND: Increasing routine HIV testing among key populations is a public
      health imperative, so improving access to acceptable testing options for those in
      need is a priority. Despite increasing targeted distribution and uptake of HIV
      self-sampling kits (SSKs) among men who have sex with men in the UK, little is
      known about why targeted SSK interventions for black African users are not as
      wide-spread or well-used. This paper addresses this key gap, offering insight
      into why some groups may be less likely than others to adopt certain types of SSK
      interventions in particular contexts. These data were collected during the
      development phase of a larger study to explore the feasibility and acceptability
      of targeted distribution of SSKs to black African people. METHODS: We undertook 6
      focus groups with members of the public who self-identified as black African (n =
      48), 6 groups with specialists providing HIV and social services to black African
      people (n = 53), and interviews with HIV specialist consultants and policy-makers
      (n = 9). Framework analysis was undertaken, using inductive and deductive
      analysis to develop and check themes. RESULTS: We found three valuable components
      of targeted SSK interventions for this population: the use of settings and
      technologies that increase choice and autonomy; targeted offers of HIV testing
      that preserve privacy and do not exacerbate HIV stigma; and ensuring that the
      specific kit being used (in this case, the TINY vial) is perceived as simple and
      reliable. CONCLUSIONS: This unique and rigorous research offers insights into
      participants' views on SSK interventions, offering key considerations when
      targeting this population.. Given the plethora of HIV testing options, our work
      demonstrates that those commissioning and delivering SSK interventions will need
      to clarify (for users and providers) how each kit type and intervention design
      adds value. Most significantly, these findings demonstrate that without a strong
      locus of control over their own circumstances and personal information, black
      African people are less likely to feel that they can pursue an HIV test that is
      safe and secure. Thus, where profound social inequalities persist, so will
      inequalities in HIV testing uptake - by any means.

PMID- 29653537
TI  - Achieving successful community engagement: a rapid realist review.
AB  - BACKGROUND: Community engagement is increasingly seen as crucial to achieving
      high quality, efficient and collaborative care. However, organisations are still
      searching for the best and most effective ways to engage citizens in the shaping
      of health and care services. This review highlights the barriers and enablers for
      engaging communities in the planning, designing, governing, and/or delivering of
      health and care services on the macro or meso level. It provides policymakers and
      professionals with evidence-based guiding principles to implement their own
      effective community engagement (CE) strategies. METHODS: A Rapid Realist Review
      was conducted to investigate how interventions interact with contexts and
      mechanisms to influence the effectiveness of CE. A local reference panel,
      consisting of health and care professionals and experts, assisted in the
      development of the research questions and search strategy. The panel's input
      helped to refine the review's findings. A systematic search of the peer-reviewed
      literature was conducted. RESULTS: Eight action-oriented guiding principles were
      identified: Ensure staff provide supportive and facilitative leadership to
      citizens based on transparency; foster a safe and trusting environment enabling
      citizens to provide input; ensure citizens' early involvement; share decision
      making and governance control with citizens; acknowledge and address citizens'
      experiences of power imbalances between citizens and professionals; invest in
      citizens who feel they lack the skills and confidence to engage; create quick and
      tangible wins; take into account both citizens' and organisations' motivations.
      CONCLUSIONS: An especially important thread throughout the CE literature is the
      influence of power imbalances and organisations' willingness, or not, to address
      such imbalances. The literature suggests that 'meaningful participation' of
      citizens can only be achieved if organisational processes are adapted to ensure
      that they are inclusive, accessible and supportive of citizens.

PMID- 29653538
TI  - Route, early or energy? ... Protein improves protein balance in critically ill
      patients.

PMID- 29653539
TI  - The phospholipase DDHD1 as a new target in colorectal cancer therapy.
AB  - BACKGROUND: Our previous study demonstrates that Citrus-limon derived
      nanovesicles are able to decrease colon cancer cell viability, and that this
      effect is associated with the downregulation of the intracellular phospholipase
      DDHD domain-containing protein 1 (DDHD1). While few studies are currently
      available on the contribution of DDHD1 in neurological disorders, there is no
      information on its role in cancer. This study investigates the role of DDHD1 in
      colon cancer. METHODS: DDHD1 siRNAs and an overexpression vector were transfected
      into colorectal cancer and normal cells to downregulate or upregulate DDHD1
      expression. In vitro and in vivo assays were performed to investigate the
      functional role of DDHD1 in colorectal cancer cell growth. Quantitative
      proteomics using SWATH-MS was performed to determinate the molecular effects
      induced by DDHD1 silencing in colorectal cancer cells. RESULTS: The results
      indicate that DDHD1 supports colon cancer cell proliferation and survival, since
      its downregulation reduces in vitro colon cancer cell viability and increases
      apoptosis rate, without affecting normal cells. On the contrary, in vivo studies
      demonstrate that the xenograft tumors, derived from DDHD1-overexpressing cells,
      have a higher proliferation rate compared to control animals. Additionally, we
      found that functional categories, significantly affected by DDHD1 silencing, were
      specifically related to cancer phenotype and for the first time associated to
      DDHD1 activity. CONCLUSIONS: In conclusion, this study provides the first
      evidence confirming the role of DDHD1 in cancer, providing a possibility to
      define a new target to design more effective therapies for colon cancer patients.

PMID- 29653540
TI  - Clinical manifestation and arthroscopic treatment of symptomatic posterior
      cruciate ligament cyst.
AB  - BACKGROUND: Ganglion cyst of cruciate ligaments is a rare lesion; the prevalence
      is 0.3-0.8%. The purpose of this study was to present clinical features of
      symptomatic posterior cruciate ligament (PCL) cyst, introduce the arthroscopic
      excision technique, and evaluate the clinical outcome. METHODS: A series of 11
      patients with symptomatic PCL cyst from November 2012 to December 2014 were
      involved in this retrospective study. Detailed medical history collecting and
      physical examination were conducted. Magnetic resonance imaging (MRI) scan was
      used to confirm the diagnosis. Arthroscopic resection was performed, and the
      sample of the cyst was taken for pathologic examination. The follow-up averaged
      30.7 months. International Knee Documentation Committee (IKDC) score, the range
      of motion (ROM), and MRI evaluations were obtained pre- and postoperatively to
      assess the surgical outcome. SPSS software was used for statistics analysis.
      RESULTS: Eight males and 3 females with 6 left knees and 5 right knees were
      enrolled, the mean age was 34.4 years, and the duration of symptom was 19.0
      months. All cases had a definite history of knee trauma or injury. The most
      common symptom was knee pain at flexion or in flexion-associated activities. MRI
      revealed the location and size of the cyst in each case. Pathologic examination
      showed the cyst wall was composed of dense fibroconnective tissue and widespread
      thick bundles of collagen, which is similar to the structure of ganglion cyst. At
      the final follow-up, MRI evaluation showed no cyst recurrence. The preoperative
      ROM and IKDC score were 2.3 degrees  to 108.6 degrees  and 40.5 +/- 11.3,
      respectively, compared with the postoperative ROM and IKDC score which were 0
      degrees  to 134.1 degrees  and 85.5 +/- 4.8 (p < 0.05) separately. CONCLUSIONS:
      We conclude that the etiology of symptomatic PCL cyst is most likely associated
      with trauma, pain on flexion is a typical manifestation of symptomatic PCL cyst,
      MRI evaluation is an ideal examination for the diagnosis, and arthroscopic
      resection of symptomatic PCL cysts has a good outcome with no recurrence.

PMID- 29653541
TI  - Cosmetic outcome as rated by patients, doctors, nurses and BCCT.core software
      assessed over 5 years in a subset of patients in the TARGIT-A Trial.
AB  - BACKGROUND: The purpose of this research was to assess agreement between four
      rating systems of cosmetic outcome measured in a subset of patients with early
      breast cancer participating in the randomised TARGIT-A trial. TARGIT-A compared
      risk-adapted single-dose intra-operative radiotherapy (TARGIT-IORT) to whole
      breast external beam radiotherapy (EBRT). METHODS: Patients, their Radiation
      Oncologist and Research Nurse completed a subjective cosmetic assessment
      questionnaire before radiotherapy and annually thereafter for five years.
      Objective data previously calculated by the validated BCCT.core software which
      utilizes digital photographs to score symmetry, colour and scar was also used.
      Agreement was assessed by the Kappa statistic and longitudinal changes were
      assessed by generalized estimating equations. RESULTS: Overall, an Excellent-Good
      (EG) cosmetic result was scored more often than a Fair-Poor (FP) result for both
      treatment groups across all time points, with patients who received TARGIT-IORT
      scoring EG more often than those who received EBRT however this was statistically
      significant at Year 5 only. There was modest agreement between the four rating
      systems with the highest Kappa score being moderate agreement which was between
      nurse and doctor scores at Year 1 with Kappa = 0.46 (p < 0.001), 95% CI (0.24,
      0.68). CONCLUSION: Despite similar overall findings between treatment groups and
      rating systems, the inter-rater agreement was only modest. This suggests that the
      four rating systems utilized may not necessarily be used interchangeably and it
      is arguable that for an outcome such as cosmetic appearance, the patient's point
      of view is the most important. TRIAL REGISTRATION: TARGIT-A ISRCTN34086741 ,
      Registered 21 July 2004, retrospectively registered.

PMID- 29653542
TI  - Decreased outlet angle of the superior cerebellar artery as indicator for
      dolichoectasia in late onset Pompe disease.
AB  - BACKGROUND: Lysosomal alpha-glucosidase deficiency (Pompe disease) not only leads
      to glycogen accumulation in skeletal muscle, but also in the cerebral arteries.
      Dolichoectasia of the basilar artery (BA) has been frequently reported. Therefore
      progression of BA dolichoectasia in late onset Pompe patients (LOPD) was studied.
      METHODS: BA length, diameter and volume, and cerebral lesions were analysed by
      MRI/TOF-MR angiography or CT/CT angiography in 20 LOPD patients and 40 controls
      matching in age, sex- and cardiovascular risk factors. The height of BA
      bifurcation was assessed semi-quantitatively using the Smoker's criteria and
      quantitatively by measuring the outlet angle of the superior cerebellar artery
      (SUCA). Nine patients were followed over 5 years. RESULTS: The height of the BA
      bifurcation was abnormal in 12/20 (60%) LOPD patients and in 12/40 (30%) matched
      controls. The SUCA outlet angle was reduced in LOPD patients compared to controls
      (127 +/- 33 degrees  vs. 156 +/- 32 degrees , p = 0.0024). The diameter, length
      and volume of the BA were significantly increased in LOPD patients compared to
      controls. 12/20 (60%) LOPD patients and 27/40 (68%) controls presented white
      matter lesions. During 5 years 2/9 LOPD patients developed an abnormal height of
      BA bifurcation according to the Smoker's criteria and in all patients the SUCA
      outlet angle decreased (138 +/- 34 degrees  vs. 128 +/- 32 degrees , p = 0.019).
      One patient with prominent basilar dolichoectasia experienced a thalamic
      hemorrhage. CONCLUSION: Pompe disease is associated with BA dilation, elongation
      and elevated bifurcation height of the BA which might result in cerebrovascular
      complications. The SUCA outlet angle seems to be useful for monitoring the
      progression of BA dolichoectasia.

PMID- 29653543
TI  - The effect of sugar and processed food imports on the prevalence of overweight
      and obesity in 172 countries.
AB  - BACKGROUND: Studies find that economic, political, and social globalization - as
      well as trade liberalization specifically - influence the prevalence of
      overweight and obesity in countries through increasing the availability and
      affordability of unhealthful food. However, what are the mechanisms that connect
      globalization, trade liberalization, and rising average body mass index (BMI)? We
      suggest that the various sub-components of globalization interact, leading
      individuals in countries that experience higher levels of globalization to
      prefer, import, and consume more imported sugar and processed food products than
      individuals in countries that experience lower levels of globalization. METHOD:
      This study codes the amount of sugar and processed food imports in 172 countries
      from 1995 to 2010 using the United Nations Comtrade dataset. We employ country
      specific fixed effects (FE) models, with robust standard errors, to examine the
      relationship between sugar and processed foods imports, globalization, and
      average BMI. To highlight further the relationship between the sugar and
      processed food import and average BMI, we employ a synthetic control method to
      calculate a counterfactual average BMI in Fiji. CONCLUSION: We find that sugar
      and processed food imports are part of the explanation to increasing average BMI
      in countries; after controlling for globalization and general imports and
      exports, sugar and processed food imports have a statistically and substantively
      significant effect in increasing average BMI. In the case of Fiji, the increased
      prevalence of obesity is associated with trade agreements and increased imports
      of sugar and processed food. The counterfactual estimates suggest that sugar and
      processed food imports are associated with a 0.5 increase in average BMI in Fiji.

PMID- 29653544
TI  - Bone marrow suppression as a complication of total skin helical tomotherapy in
      the treatment of mycosis fungoides.
AB  - BACKGROUND: Total skin electron beam therapy (TSEBT) is an effective treatment in
      mycosis fungoides. Total skin helical tomotherapy (TSHT) may be an alternative to
      TSEBT and may offer several dosimetric and treatment advantages. There are
      currently very few published treatment results using TSHT in place of TSEBT for
      treatment of mycosis fungoides. CASE PRESENTATION: Two patients with mycosis
      fungoides were treated at our institution using TSHT. The first patient was a 69
      year-old Caucasian female with stage IVA2 (T2 N3 M0 B2) disease who was treated
      to a dose of 12 Gy in 8 fractions, with a bone marrow mean dose of 1.66 Gy and
      V10 = 0.41%. Two weeks after ending treatment the patient developed
      myelosuppression including grade 4 thrombocytopenia and required blood and
      platelet transfusions. The second patient was a 29-year-old Caucasian female with
      stage I (T2 N0 M0 B0) disease. This patient previously had been treated for
      mycosis fungoides using helical tomotherapy (HT) at a dose of 20 Gy to a
      localized region and experienced mild thrombocytopenia at that time. The patient
      then underwent retreatment 17 months later with TSHT to a dose of 12 Gy in 6
      fractions with a mean bone marrow dose of 2.3 Gy and V10 = 4.28%. This patient
      once again experienced myelosuppression that included grade 4 thrombocytopenia.
      She also required blood and platelet transfusions. CONCLUSIONS: Both patients
      treated with TSHT experienced severe bone marrow suppression including grade 4
      thrombocytopenia. This was more severe than expected considering the relatively
      low overall prescription dose and despite a planning constraint placed on the
      bone marrow of a mean dose of < 2 Gy. These outcomes suggest that patients
      treated using TSHT should be closely monitored for myelosuppression and caution
      used even when treating to a dose of 12 Gy.

PMID- 29653545
TI  - Effectiveness of school dental screening on dental visits and untreated caries
      among primary schoolchildren: study protocol for a cluster randomised controlled
      trial.
AB  - BACKGROUND: Dental caries is one of the most common diseases affecting children
      in Saudi Arabia despite the availability of free dental services. School-based
      dental screening could be a potential intervention that impacts uptake of dental
      services, and subsequently, dental caries' levels. The purpose of this study is
      to evaluate the effectiveness of two alternative approaches for school-based
      dental screening in promoting dental attendance and reducing untreated dental
      caries among primary schoolchildren. METHODS: This is a cluster randomised
      controlled trial comparing referral of screened-positive children to a specific
      treatment facility (King Saud University Dental College) against conventional
      referral (information letter advising parents to take their child to a dentist).
      A thousand and ten children in 16 schools in Riyadh, Saudi Arabia, will be
      recruited for the trial. Schools (clusters) will be randomly selected and
      allocated to either group. Clinical assessment for dental caries will be
      conducted at baseline and after 12 months by dentists using the World Health
      Organisation (WHO) criteria. Data on sociodemographic, behavioural factors and
      children's dental visits will be collected through structured questionnaires at
      baseline and follow-up. The primary outcome is the change in number of teeth with
      untreated dental caries 12 months after referral. Secondary outcomes are the
      changes in the proportions of children having untreated caries and of those who
      visited the dentist over the trial period. DISCUSSION: This project should
      provide high level of evidence on the clinical benefits of school dental
      screening. The findings should potentially inform policies related to the
      continuation/implementation of school-based dental screening in Saudi Arabia.
      TRIAL REGISTRATION: ClinicalTrials.gov , ID: NCT03345680 . Registered on 17
      November 2017.

PMID- 29653546
TI  - Diagnostic accuracy of blood sucrose as a screening test for equine gastric ulcer
      syndrome (EGUS) in weanling foals.
AB  - BACKGROUND: Equine gastric ulcer syndrome is an important cause of morbidity in
      weanling foals. Many foals are asymptomatic, and the development of an
      inexpensive screening test to ensure an early diagnosis is desirable. The
      objective of this study was to determine the diagnostic accuracy of blood sucrose
      for diagnosis of EGUS in weanling foals. RESULTS: 45 foals were studied 7 days
      before and 14 days after weaning. The diagnostic accuracy of blood sucrose for
      diagnosis of gastric lesions (GL); glandular lesions (GDL); squamous lesions
      (SQL) and clinically significant gastric lesions (CSL) at 45 and 90 min after
      administration of 1 g/kg of sucrose via nasogastric intubation was assessed using
      ROC curves and calculating the AUC. For each lesion type, sucrose concentration
      in blood was compared to gastroscopy; and sensitivities (Se) and specificities
      (Sp) were calculated across a range of sucrose concentrations. Cut-off values
      were selected manually to optimize Se. Because of concerns over the validity of
      the gold standard, additional Se, Sp, and lesion prevalence data were
      subsequently estimated and compared using Bayesian latent class analysis. Using
      the frequentist approach, the prevalence of GL; GDL; SQL and CSL before weaning
      was 21; 9; 7 and 8% respectively; and increased to 98; 59; 97 and 82%
      respectively after weaning. At the selected cut-off, Se ranged from 84 to 95% and
      Sp ranged from 47 to 71%, depending upon the lesion type and time of sampling. In
      comparison, estimates of Se and Sp were consistently higher when using a Bayesian
      approach, with Se ranging from 81 to 97%; and Sp ranging from 77 to 97%,
      depending upon the lesion type and time of sampling. CONCLUSIONS: Blood sucrose
      is a sensitive test for detecting EGUS in weanling foals. Due to its poor
      specificity, it is not expected that the sucrose blood test will replace
      gastroscopy, however it may represent a clinically useful screening test to
      identify foals that may benefit from gastroscopy. Bayesian latent class analysis
      represents an alternative method to evaluate the diagnostic accuracy of the blood
      sucrose test in an attempt to avoid bias associated with the assumption that
      gastroscopy is a perfect test.

PMID- 29653547
TI  - Wicked problems and a 'wicked' solution.
AB  - BACKGROUND: 'Wicked' is the term used to describe some of the most challenging
      and complex issues of our time, many of which threaten human health. Climate
      change, biodiversity loss, persisting poverty, the advancing obesity epidemic,
      and food insecurity are all examples of such wicked problems. However there is a
      strong body of evidence describing the solutions for addressing many of these
      problems. Given that much is known about how many of these problems could be
      addressed - and given the risks of not acting - what will it take to create the
      'tipping point' needed for effective action? MAIN BODY: A recent (2015) court
      ruling in The Hague held that the Dutch government's stance on climate change was
      illegal, ordering them to cut greenhouse gas emissions by at least 25% within 5
      years (by 2020), relative to 1990 levels. The case was filed on behalf of 886
      Dutch citizens, suing the government for violating human rights and climate
      changes treaties by failing to take adequate action to prevent the harmful
      impacts of climate change. This judicial ruling has the potential to provide a
      way forward, inspiring other civil movements and creating a template from which
      to address other wicked problems. CONCLUSION: This judicial strategy to address
      the need to lower greenhouse gas emissions in the Netherlands is not a magic
      bullet, and requires a particular legal and institutional setting. However it has
      the potential to be a game-changer - providing an example of a strategy for
      achieving domestic regulatory change that is likely to be replicable in some
      countries elsewhere, and providing an example of a particularly 'wicked' (in the
      positive, street-slang sense of the word) strategy to address seemingly
      intractable and wicked problems.

PMID- 29653549
TI  - Response to "in regard to "Tran A, Zhang J, Woods K, Yu V, Nguyen D, Gustafson G,
      Rosen L, Sheng K. Treatment planning comparison of IMPT, VMAT and 4pi
      radiotherapy for prostate cases"".
AB  - In regard to our recently published paper entitled "Treatment planning comparison
      of IMPT, VMAT and 4pi radiotherapy for prostate cases", a question was raised
      whether "4pi" was used appropriately to describe the non-coplanar planning and
      delivery space. In this letter, the term use is explained from both theoretical
      and practical perspectives. It is concluded that the self-explanatory term
      provides a flexible description of non-coplanar radiotherapy with beam
      orientation optimization. Confusions with this term can be avoided by
      understanding the evolving and machine/patient specific nature of 4pi planning.

PMID- 29653550
TI  - Mecasin treatment in patients with amyotrophic lateral sclerosis: study protocol
      for a randomized controlled trial.
AB  - BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative
      disease that causes paralysis of limb, swallowing, and breathing muscles.
      Riluzole, the Food and Drug Administration-approved drug for ALS, provides
      minimal benefit, prolonging patient life by only 2-3 months. Previous studies
      have found a neuro-protective and anti-neuroinflammatory effect of Mecasin, with
      retrospective studies providing suggestive evidence for a beneficial effect of
      Mecasin. The aim of this study was to develop a protocol to determine the proper
      dosage of Mecasin. METHODS: This is a phase II-A, multi-center, randomized study
      with three arms. Thirty-six patients with ALS will be randomly assigned to one of
      three groups, each receiving the standard treatment with 100 mg of riluzole in
      addition to one of 1.6 g of Mecasin, 2.4 g of Mecasin, or a placebo. The Primary
      outcome is the Korean version of the Amyotrophic Lateral Sclerosis Functional
      Rating Scale-Revised result after 12 weeks of treatment. Secondary outcomes
      include results of the Short Form Health Survey-8, Medical Research Council
      Scale, Visual Analogue Scale for Pain, Hamilton Rating Scale for Depression,
      Fatigue Severity Scale, Patient Global Impression of Change, pulmonary function
      test, forced expiratory volume in 1 s and its ratio to forced vital capacity,
      creatine kinase, and body weight. The frequencies of total adverse events and
      serious adverse events will be described and documented. The trial protocol has
      been approved by the Institutional Review Board of the Wonkwang University
      Gwangju and Sanbon Hospital (2016-5-4 and 2016-34-01, respectively). An
      Investigational New Drug status (30731) was granted by the Korea Food and Drug
      Administration. DISCUSSION: This trial will aim to identify the optimal dosage of
      Mecasin. Additionally, it will test the efficacy and safety of Mecasin in
      conjunction with standard treatment, riluzole, for alleviating the functional
      decline in patients with ALS. TRIAL REGISTRATION: Korean National Clinical Trial
      Registry CRIS; KCT0001984 . Registered on 28 July 2016.

PMID- 29653551
TI  - Open pelvic fracture: the killing fracture?
AB  - BACKGROUND: Open pelvic fractures are rare but represent a serious clinical
      problem with high mortality rates. The purpose of this study was to evaluate the
      outcomes of open pelvic fractures in our clinic and to compare the results from
      our patient group with those of closed fractures and with the literature from the
      past decade. METHODS: Data of patients older than 16 years of age who were
      admitted to our hospital with a pelvic fracture between January 1, 2004, and
      December 31, 2014, were analyzed. The collected data were patient demographics,
      mechanism of injury, RTS, ISS, transfusion requirement during the first 24 h,
      Gustilo-Anderson and Faringer classification, number and type of interventions
      complications, mortality, and length of stay. RESULTS: Twenty-four of 492
      patients (5% of all pelvic fracture patients) had an open fracture. Their mean
      age was 36 years, the mean ISS was 31, and the mean number of transfused packed
      red blood cells was 5.5. These numbers were all significantly higher than in the
      patients with a closed fracture, although they were comparable to other studies
      with open fractures. The mortality was 4% in the open group versus 14% in the
      closed group (p = 0.23). The reported mortality in the literature ranges between
      4 and 45%. CONCLUSION: Open pelvic fractures are relatively rare but are a cause
      of significant morbidity. In this series, we treated patients with open pelvic
      fractures successfully, with a survival rate of 96%. There was no significant
      difference in survival rate between open and closed pelvic fractures. Compared
      with other studies, the mortality in our study was relatively low.

PMID- 29653548
TI  - Linking neuronal lineage and wiring specificity.
AB  - Brain function requires precise neural circuit assembly during development.
      Establishing a functional circuit involves multiple coordinated steps ranging
      from neural cell fate specification to proper matching between pre- and post
      synaptic partners. How neuronal lineage and birth timing influence wiring
      specificity remains an open question. Recent findings suggest that the
      relationships between lineage, birth timing, and wiring specificity vary in
      different neuronal circuits. In this review, we summarize our current
      understanding of the cellular, molecular, and developmental mechanisms linking
      neuronal lineage and birth timing to wiring specificity in a few specific systems
      in Drosophila and mice, and review different methods employed to explore these
      mechanisms.

PMID- 29653552
TI  - Independent prognostic genes and mechanism investigation for colon cancer.
AB  - PROPOSE: We aimed to explore the potential molecular mechanism and independent
      prognostic genes for colon cancer (CC). METHODS: Microarray datasets GSE17536 and
      GSE39582 were downloaded from Gene Expression Omnibus. Meanwhile, the whole CC
      related dataset were downloaded from The Cancer Genome Atlas (TCGA) database.
      Differentially expressed mRNA (DEMs) were identified between cancer tissue
      samples and para-carcinoma tissue samples in TCGA dataset, followed by the KEGG
      pathway and GO function analyses. Furthermore, the clinical prognostic analysis
      including overall survival (OS) and disease-free survival (DFS) were performed in
      all three datasets. RESULTS: A total of 633 up- and 321 down-regulated mRNAs were
      revealed in TCGA dataset. The up-regulated mRNAs were mainly assembled in
      functions including extracellular matrix and pathways including Wnt signaling.
      The down-regulated mRNAs were mainly assembled in functions like Digestion and
      pathways like Drug metabolism. Furthermore, up-regulation of UL16-binding protein
      2 (ULBP2) was associated with OS in CC patients. A total of 12 DEMs including
      Surfactant Associated 2 (SFTA2) were potential DFS prognostic genes in CC
      patients. Meanwhile, the GRP and Transmembrane Protein 37 (TMEM37) were two
      outstanding independent DFS prognostic genes in CC. CONCLUSIONS: ULBP2 might be a
      potential novel OS prognostic biomarker in CC, while GRP and TMEM37 could be
      served as the independent DFS prognostic genes in CC. Furthermore, functions
      including extracellular matrix and digestion, as well as pathways including Wnt
      signaling and drug metabolism might play important roles in the process of CC.

PMID- 29653553
TI  - Promoting and sustaining a historical and global effort to prevent sepsis: the
      2018 World Health Organization SAVE LIVES: Clean Your Hands campaign.
AB  - Sepsis is estimated to affect more than 30 million patients with potentially five
      million deaths every year worldwide. Prevention of sepsis, as well as early
      recognition, diagnosis and treatment, can't be overlooked to mitigate this global
      public health threat. World Health Organization (WHO) promotes hand hygiene in
      health care through its annual global campaign, SAVE LIVES: Clean Your Hands
      campaign on 5 May every year. The 2018 campaign targets sepsis with the overall
      theme "It's in your hands; prevent sepsis in health care".

PMID- 29653554
TI  - Does full sternotomy have more significant impact than the cardiopulmonary bypass
      time in patients of mitral valve surgery?
AB  - BACKGROUND: Over the past decade, minimally invasive mitral valve surgery (MIMVS)
      has grown in popularity. Less invasive approaches to mitral valve surgery are
      increasingly used for improved cosmesis. We sought to compare these minimally
      invasive approaches fairly with conventional full sternotomy approaches by using
      propensity-matching methods. METHODS: From January 2011 to January 2017, a total
      of 1120 isolated mitral valve operations were performed at our institution. Data
      were retrospectively collected on all patients, and a logistic regression model
      was created to predict selection to a minimally invasive versus conventional
      sternotomy approach. Propensity scores were then generated based on the
      regression model and matched pairs created using 1:1 nearest neighbor matching.
      There were 165 matched pairs in the analysis (sternotomy, n = 165;MIMVS, n =
      165). Clinical outcomes included bypass and cross-clamp time, length of
      hospitalization, morbidity, and mortality. Patient details and follow-up outcomes
      were compared using multivariate, and Kaplan-Meier analyses. RESULTS: The
      minimally invasive approach led to slightly longer cardiopulmonary bypass time
      (99 +/- 25 vs 88 +/- 17 min, p <0.001), and cross-clamp time (65 +/- 13 vs 49 +/-
      11 min, p<0.001). Overall, no significant differences existed among major in
      hospital complications between groups. There were no differences between the
      matched groups in 30-day mortality (1.2% vs 0.6%, p >0.05). However, Chest tube
      drainage was lower at 6 and 24 h after a minimally invasive approach (30 +/- 5
      mL) and 120 +/- 20 mL than after conventional sternotomy 175 +/- 50 mL and 400 +/
      150 mL at these times (p < 0.001). Transfusion was less frequent after minimally
      invasive surgery than after conventional surgery (15.7% vs 40.6%, p < 0.001).
      Patients undergoing minimally invasive surgery spent less time on ventilation
      support (6.2 +/- 1.1 h vs 10.4 +/- 2.7, p < 0.001). The multivariable regression
      analysis showed the full sternotomy was an independent risk factor for the
      propensity-adjusted likelihood of postoperative transfusion, re-exploration for
      bleeding, and postoperative ventilation support (p < 0.05). But the duration of
      cardiopulmonary bypass time was not an independent risk factor. The mean duration
      of survival follow-up was 4.4 +/- 1.2 years. However, comparison of survival
      curves between the two groups revealed no significant difference (P = 0.203).
      With regard to freedom from valve-related morbidity, there was no significant
      difference between groups (P = 0 .574). CONCLUSION: Within that portion of the
      spectrum of mitral valve surgery in which propensity matching was possible,
      minimally invasive mitral valve surgery has cosmetic, blood product use, and
      respiratory advantages over conventional surgery, and no apparent detriments.
      However, minimally invasive mitral valve surgery required a slightly longer
      cardiopulmonary bypass time and cross-clamp time. Minimally invasive mitral valve
      surgery represents a safe and effective surgical technique that we believe should
      be used more routinely in the surgical management of mitral valve disease. MIMVS
      provides equally durable midterm results as the standard sternotomy approach.

PMID- 29653555
TI  - Feasibility of an online mindfulness-based program for patients with melanoma:
      study protocol for a randomised controlled trial.
AB  - BACKGROUND: People with a melanoma diagnosis are at risk of recurrence,
      developing a new primary or experiencing disease progression. Previous studies
      have suggested that fear of a cancer recurrence is clinically relevant in this
      group of patients and, if not addressed, can lead to distress. Mindfulness-based
      interventions have been shown to alleviate symptoms of anxiety and depression
      among various groups of cancer patients. Online mindfulness-based interventions
      have the potential to reach people unable to attend face-to-face interventions
      due to limitations such as cancer-related illness, transportation or time
      constraints. This study aims to (1) examine whether individuals with a melanoma
      diagnosis are willing to participate and adhere to a 6-week online mindfulness
      based intervention and (2) explore potential benefits of the program on fear of
      cancer recurrence, worries, rumination, perceived stress and trait mindfulness to
      inform the design of a clinical trial. METHODS/DESIGN: This is a single-site
      randomised controlled trial of a feasibility study. Seventy-five participants
      with stage 2c or 3 melanoma will be recruited from a melanoma outpatient clinic
      and randomised (2:1) either to an online mindfulness-based program (intervention)
      or to usual care (control). The intervention is a 6-week program specifically
      developed for this study. It consists of videos describing the concept of
      mindfulness, short daily guided meditation practices (5-10 min), automated
      meditation reminders and instructions for applying mindfulness in daily life to
      enhance wellbeing. All participants will complete questionnaires at baseline and
      at 6-week post-randomisation. Participants in the control group will be given
      access to the online program at the end of the study. Primary outcomes are
      overall recruitment; retention; extent of questionnaire completion; and usability
      and acceptability of, and adherence to, the program. The secondary outcomes are
      fear of cancer recurrence, worries, rumination, perceived stress and trait
      mindfulness measured using validated instruments. DISCUSSION: This feasibility
      study will evaluate participants' satisfaction with the program and identify
      barriers to recruitment and adherence. The recruitment and data collection
      process will highlight methodological aspects to address in the planning of a
      larger scale study assessing the impact of an online mindfulness-based
      intervention on fear of cancer recurrence and wellbeing. TRIAL REGISTRATION:
      Australian New Zealand Clinical Trials Registry, ACTRN12617000081314 . Registered
      on 16 January 2017.

PMID- 29653557
TI  - Impact of Myeloproliferative neoplasms on patients' employment status and work
      productivity in the United States: results from the living with MPNs survey.
AB  - BACKGROUND: Patients with the myeloproliferative neoplasms (MPNs) myelofibrosis
      (MF), polycythemia vera (PV), and essential thrombocythemia (ET) are at increased
      risk for thrombotic and cardiovascular events and experience a variety of
      burdensome symptoms. However, there is a paucity of data in the biomedical
      literature about how MPNs impact productivity in the workplace. This analysis of
      the Living with MPNs survey was conducted to evaluate the impact of MPNs on
      employment, career potential, and work productivity. METHODS: This cross
      sectional online survey included respondents aged 18-70 years living in the
      United States with a diagnosis of MF, PV, or ET. The survey consisted of ~ 100
      questions related to MPN diagnosis, disease-related medical history, MPN-related
      symptoms and functional status, changes in employment and work productivity, and
      impact on daily activities since diagnosis. The MPN Symptom Assessment Form Total
      Symptom Score (MPN-SAF TSS) was used to assess symptom burden. The Work
      Productivity and Activity Impairment Specific Health Problem questionnaire (WPAI
      SHP) was used to assess the effects of MPNs on work productivity and activity (7
      day recall) among currently employed respondents. Correlations between MPN-SAF
      TSS and WPAI-SHP scores were calculated using Spearman's coefficients. RESULTS:
      Of 904 respondents, 592 were employed (MF, n = 174; PV, n = 248; ET, n = 170) at
      the time of their MPN diagnosis. Approximately half (50.5%) of the 592 employed
      survey respondents reported >=1 change in employment status because of their
      diagnosis, most commonly "left a job" (30.2%) "went on medical disability leave"
      (24.8%), and "had reductions in work hours for at least 3 months" (21.8%). Among
      respondents who remained employed at the time of survey participation (n = 398),
      mean WPAI-SHP scores were as follows: absenteeism, 6.9%; presenteeism, 27.4%;
      overall work impairment, 31.1%; and activity impairment, 32.8%. WPAI-SHP scores
      positively correlated with MPN-SAF TSS (correlation coefficients, 0.37-0.70; P <
      0.001). CONCLUSIONS: Half of the employed respondents had an employment status
      change (eg, leaving a job, medical disability leave, early retirement) because of
      their disease since the diagnosis. Currently employed respondents reported
      meaningful impairments in work productivity and activities of daily living that
      were attributable to their MPNs, and the degree of impairments highlighted the
      severity of symptom burden.

PMID- 29653556
TI  - Non-endometrioid and high-grade endometrioid endometrial cancers show DNA
      fragmentation factor 40 (DFF40) and B-cell lymphoma 2 protein (BCL2)
      underexpression, which predicts disease-free and overall survival, but not DNA
      fragmentation factor 45 (DFF45) underexpression.
AB  - BACKGROUND: The expression of DNA fragmentation factor 45 (DFF45) and B-cell
      lymphoma 2 (BCL2) in glands of the normal human endometrium is related to phases
      of the menstrual cycle and decreases after menopause, whereas the expression of
      DNA fragmentation factor 40 (DFF40) is stable. Moreover, DF45, BCL2 and DFF40
      underexpression has been reported in numerous malignancies, including uterine
      leiomyosarcomas. In this study, we aimed to investigate DFF45, BCL2 and DFF40
      expression in endometrioid and non-endometrioid types of endometrial cancers
      (ECs). We also evaluated the correlations between DFF45, BCL2 and DFF40
      expression levels and clinicopathological parameters and determined the value of
      these three proteins as prognostic markers of disease-free survival (DFS) and
      overall survival (OS). METHODS: Immunohistochemistry was performed to evaluate
      DFF45, BCL2 and DFF40 expression in 342 cases of ECs. Student's t-test, the Mann
      Whitney U-test, and the chi-squared test were used for the statistical analyses
      as appropriate. The Cox-Mantel test, Cox's proportional hazard model, and
      relative risk analyses were used to evaluate associations between DFF40, DFF45,
      and BCL2 expression and clinicopathological characteristics. RESULTS: DFF40 and
      BCL2, but not DFF45, were significantly underexpressed in non-endometrioid and
      high-grade endometrioid ECs compared with low- and moderate-grade endometrioid
      ECs. Women with DFF40- and BCL2-negative tumors had higher risks of disease
      recurrence, lymph node involvement, lympho-vascular space infiltration, and deep
      myometrial invasion compared with women with DFF40- and BCL2-positive tumors.
      Additionally, women with DFF40- and BCL2-negative tumors had significantly lower
      OS and DFS than women with DFF40- and BCL2-positive tumors. A multivariable
      analysis of the model, including the clinicopathological characteristics and
      immunohistochemical results, showed that negative BCL2 expression, lymph node
      involvement, and high-stage and high-grade disease were independent predictors of
      OS, whereas negative BCL2 expression, lymph node involvement, and high-stage
      disease were independent predictors of DFS. CONCLUSIONS: Compared with low- and
      moderate-grade endometrioid ECs, non-endometrioid and high-grade endometrioid ECs
      showed significant DFF40 and BCL2 underexpression. The absence of DFF40 and BCL2
      expression negatively affects DFS and OS. Further prospective studies are
      warranted to assess the potential utility of DFF40 and BCL2 as targets in the
      diagnosis or treatment of ECs.

PMID- 29653558
TI  - Acute hydrops with a 180-degree massive edematous cavern demonstrated by three
      dimensional view of anterior segment optical coherence tomography in a patient
      with pellucid marginal corneal degeneration, a case report.
AB  - BACKGROUND: Pellucid marginal corneal degeneration is a non-inflammatory disorder
      complicated by severe inferior corneal thinning. The central portion of the
      cornea, consequently, appears to protrude outwards, decreasing vision by means of
      an irregular stigmatism. Additionally, acute hydrops can occur in case of
      Descemet's membrane rupture. CASE PRESENTATION: A 41-year-old Japanese woman
      presenting with severe visual loss in the left eye was examined and observed to
      have had full thickness corneal perforation as well as a Descemet membrane
      rupture with massive edema in the corneal stroma. Anterior segment optical
      coherence tomography-based corneal topography revealed a distorted crab claw sign
      indicating pellucid marginal corneal degeneration. The Descemet membrane rupture
      allowed acute hydrops to occur which was especially noteworthy given the scale of
      edema present within the stroma, rotating 180 degrees along the limbus, causing a
      smiley-face like lesion. We visualized it via a gonioscopic three-dimensional
      optical coherence tomography to build a three-dimensional video. Patient history
      revealed a previous acute hydrops in the right eye as well, which was ultimately
      treated with anterior lamellar keratoplasty, suggesting the pellucid marginal
      corneal degeneration had a classic bilateral involvement, which was also
      characterized with bilateral acute hydrops. CONCLUSION: This appears to be a very
      rare and interesting presentation of bilateral pellucid marginal degeneration,
      wherein not only acute hydrops formed bilaterally, but the cavity within the
      cornea stroma was exceptionally large with an unusual shape. Using the
      gonioscopic three-dimensional optical coherence tomography imaging, we were able
      to easily visualize the massive intrastromal cavern, and appropriately planned
      the crescent-shaped anterior lamellar keratoplasty. The 3d video constructed
      using this data is particularly elucidative compared to 2d images. As such, we
      recommend utilizing 3d imaging in cases where more conventional topography is not
      as explanatory with respect to precise nature of deformation.

PMID- 29653559
TI  - Serum microRNA signatures and metabolomics have high diagnostic value in gastric
      cancer.
AB  - BACKGROUND: Many novel diagnostic biomarkers have been developed for gastric
      cancer (GC) recently. We chose two methods with high diagnostic value, the
      detection of serum microRNAs and metabolomics based on gas chromatography/mass
      spectrometry (GC/MS), and aimed to establish appropriate models. METHODS: We
      reviewed the diagnostic accuracies of all microRNAs identified by previous
      diagnostic tests. Then appropriate microRNAs and their combinations were
      validated the diagnostic value. We included 80 patients with GC and 82 healthy
      controls (HCs) and detected the expression of the microRNAs. GC/MS analysis was
      conducted, and we used three multivariate statistical analyses to establish
      diagnostic models. The concentrations of carcinoembryonic antigen (CEA) and
      carbohydrate antigen 19-9 (CA19-9) were detected for comparison with the novel
      models. RESULTS: Sixty-seven published studies and 70 microRNAs were finally
      included in the systematic review. MiR-18a, miR-19a, miR-21, miR-92a, miR-199a
      and miR-421 were chosen to further validate their diagnostic efficiencies. Five
      of those microRNAs in GC patients had significantly different expression. The
      combination of miR-19a and miR-92a had the highest area under the curve (AUC) at
      0.850 with a sensitivity of 91.3% and a specificity of 61.0%. The GC/MS analysis
      performed an excellent diagnostic value and the AUC reached 1.0. CONCLUSION:
      There is a good potential for microRNAs and GC/MS analysis as new diagnostic
      methods in view of their high diagnostic value compared with traditional
      biomarkers.

PMID- 29653560
TI  - ZBP-89 and Sp1 contribute to Bak expression in hepatocellular carcinoma cells.
AB  - BACKGROUND: Kruppel family member zinc binding protein 89 (ZBP-89), also known as
      ZNF148, regulates Bak expression via binding to GC-rich promoter domain. It is
      not clear if other GC-rich binding factors, such as Sp family members, can
      interact with ZBPp-89 on Bak expression. This study aims to elucidate the
      mechanism of Bak expression regulation by ZBP-89 and Sp proteins, based on in
      vitro experiment and The Cancer Genome Atlas (TCGA) hepatocellular carcinoma
      (HCC) data cohort. METHODS: We downloaded TCGA hepatocellular carcinoma (HCC)
      cohort data to analysis the association of Bak transcription level with ZBP-89
      and Sp proteins transcription level. HCC cell lines and liver immortal non-tumour
      cell lines were used for mechanism study, including western blotting analysis,
      expression vector mediated gene expression and siRNA interference. RESULTS:
      Results showed that cancer tissues have higher Bak transcription level compared
      with adjacent non-cancer tissues. Bak transcription level was correlated with Sp1
      and Sp3 expression level, while no correlation was found in ZBP-89 and Bak,
      neither Sp2 nor Sp4. Mithramycin A (MMA) induced Bak expression in a dose
      dependent manner. Western blotting results showed Sp1 overexpression increased
      Bak expression both in liver immortal non-tumour cells and HCC cells.
      Interference Sp1 expression could inhibit Bak expression alone. ZBP-89 siRNA
      suppressed Bak expression even in the presence of MMA treatment and S1
      overexpression. Additionally, Bak and Sp1 level were associated with HCC patient
      survival. CONCLUSIONS: Bak expression required ZBP-89 and Sp1 cooperative
      regulation simultaneously.

PMID- 29653561
TI  - Micro-RNA-186-5p inhibition attenuates proliferation, anchorage independent
      growth and invasion in metastatic prostate cancer cells.
AB  - BACKGROUND: Dysregulation of microRNA (miRNA) expression is associated with
      hallmarks of aggressive tumor phenotypes, e.g., enhanced cell growth,
      proliferation, invasion, and anchorage independent growth in prostate cancer
      (PCa). METHODS: Serum-based miRNA profiling involved 15 men diagnosed with non
      metastatic (stage I, III) and metastatic (stage IV) PCa and five age-matched
      disease-free men using miRNA arrays with select targets confirmed by quantitative
      real-time PCR (qRT-PCR). The effect of miR-186-5p inhibition or ectopic
      expression on cellular behavior of PCa cells (i.e., PC-3, MDA-PCa-2b, and LNCaP)
      involved the use bromodeoxyuridine (BrdU) incorporation, invasion, and colony
      formation assays. Assessment of the impact of miR-186-5p inhibition or
      overexpression on selected targets entailed microarray analysis, qRT-PCR, and/or
      western blots. Statistical evaluation used the modified t-test and ANOVA
      analysis. RESULTS: MiR-186-5p was upregulated in serum from PCa patients and
      metastatic PCa cell lines (i.e., PC-3, MDA-PCa-2b, LNCaP) compared to serum from
      disease-free individuals or a normal prostate epithelial cell line (RWPE1),
      respectively. Inhibition of miR-186-5p reduced cell proliferation, invasion, and
      anchorage-independent growth of PC-3 and/or MDA-PCa-2b PCa cells. AKAP12, a tumor
      suppressor target of miR-186-5p, was upregulated in PC-3 and MDA-PCa-2b cells
      transfected with a miR-186-5p inhibitor. Conversely, ectopic miR-186-5p
      expression in HEK 293 T cells decreased AKAP12 expression by 30%. Both pAKT and
      beta-catenin levels were down-regulated in miR-186-5p inhibited PCa cells.
      CONCLUSIONS: Our findings suggest miR-186-5p plays an oncogenic role in PCa.
      Inhibition of miR-186-5p reduced PCa cell proliferation and invasion as well as
      increased AKAP12 expression. Future studies should explore whether miR-186-5p may
      serve as a candidate prognostic indicator and a therapeutic target for the
      treatment of aggressive prostate cancer.

PMID- 29653562
TI  - Stereotactic body radiation therapy using a respiratory-gated volumetric
      modulated arc therapy technique for small hepatocellular carcinoma.
AB  - BACKGROUND: Volumetric-modulated arc therapy (VMAT) is a highly sophisticated
      linear accelerator-based treatment method, and allows dose rate-changing
      intensity modulation with gantry rotation. We report our clinical experiences
      with stereotactic body radiation therapy (SBRT) using a respiratory-gated VMAT
      technique for patients with hepatocellular carcinoma (HCC) when established
      curative treatments cannot be applied. METHODS: A total of 119 patients (139
      lesions) with HCC who were treated with SBRT were registered between March 2012
      and July 2013 at our institution. A dose of 10-15 Gy per fraction was applied
      over 3-4 consecutive days, resulting in a total dose of 30-60 Gy. RESULTS: The
      median follow-up period was 25.8 months (range, 3.2-36.8 months). The overall 3
      year survival rate was 83.8%. The local control rate at 3 years was 97.0% in all
      treated lesions. Multivariate analysis revealed that the Child-Pugh class before
      SBRT had significant effects on overall survival (Child-Pugh A: hazard ratio =
      0.463; 95% CI, 0.262-0.817; p = 0.008). CONCLUSIONS: SBRT using a respiratory
      gated VMAT technique was an excellent ablative treatment modality for patients
      with HCC. SBRT is a good alternative treatment for patients with small HCCs that
      are unsuitable for surgical resection or local ablative therapy.

PMID- 29653563
TI  - A rabbit model of corneal Ectasia generated by treatment with collagenase type
      II.
AB  - BACKGROUND: To investigate use of collagenase type II for generating a rabbit
      model of corneal ectasia. METHODS: Ten New Zealand white rabbits were used with
      right eyes treated as the experimental group and left eyes treated as the control
      group. After epithelial debridement, a collagenase type II solution (200 MUL of 5
      mg/mL) was applied in the experimental group at room temperature (24  degrees C)
      for 30 min, and a 200 MUL solution without collagenase was applied in the control
      group. Slit-lamp microscopy, the mean keratometry (Km), and central cornea
      thickness (CCT) were examined before and after the procedure. Corneas were
      obtained on day 14 for biomechanical evaluation. RESULTS: No obvious inflammatory
      reaction was observed in all eyes after the procedure. A statistically
      significant increase in Km (1.54 +/- 1.29D vs - 0.82 +/- 0.44D at day7 and 0.89
      +/- 0.89D vs - 2.11 +/- 1.02D at day14) and a statistically significant decrease
      in CCT (- 23.10 +/- 12.17 MUm vs 6.20 +/- 16.51 MUm at day7 and - 16.10 +/- 10.46
      MUm vs 11.60 +/- 0.88 MUm at day14) were observed in the experimental group
      compared with the control group. The mean stresses and elastic modulus at 5%,
      10%, 15%, and 20% deformities in the experimental group decreased and the
      differences in elastic modulus between the two groups were statistically
      significant at 10% and 15% deformities. CONCLUSIONS: Collagenase type II
      treatment results in mimic KC with increased corneal keratometry and corneal
      thinning and a lower elastic modulus. An animal model for corneal ectasia can be
      generated by treatment with collagenase type II.

PMID- 29653564
TI  - Prognostic value of serum CYFRA 21-1 1 in patients with anal canal squamous cell
      carcinoma treated with radio(chemo)therapy.
AB  - BACKGROUND: We aimed to assess the prognostic value of CYFRA 21-1 in a series of
      patients with anal canal squamous cell carcinoma treated by radiation-based
      therapy. METHODS: All patients with anal cancer referred between September 2005
      and July 2013 were considered. Patients with diagnosis of anal squamous cell
      carcinoma and in whom pre- and post-treatment serum CYFRA 21-1 levels were
      available were included. Serum CYFRA 21-1 levels at initial workup and after
      therapy were collected. Survival rates were estimated using the Kaplan-Meier
      method. Cox regression analysis was used to evaluate prognostic variables for
      prediction of outcomes. RESULTS: Eighty-two patients were included. Median follow
      up was 60 months (range: 8-128). Pre-treatment serum CYFRA 21-1 levels were
      significantly correlated with tumour stage (p < 0.001). Normal post-treatment
      serum CYFRA 21-1 level was significantly correlated with tumour complete response
      (p = 0.004). Elevated post-treatment serum CYFRA 21-1 level was significantly
      associated with poorer progression-free survival (p = 0.02) and overall survival
      (p = 0.003). T stage and post-treatment serum CYFRA 21-1 were independent
      prognostic factors for overall survival (p = 0.04 and 0.03, respectively).
      CONCLUSIONS: Serum CYFRA 21-1 appears to be a useful marker for the monitoring of
      anal squamous cell carcinoma patients. Elevated post-treatment value appears to
      be correlated with treatment failure.

PMID- 29653565
TI  - Identification of H2O2 induced oxidative stress associated microRNAs in HLE-B3
      cells and their clinical relevance to the progression of age-related nuclear
      cataract.
AB  - BACKGROUND: This study is aimed to screen out the microRNAs (miRNAs) associated
      with H2O2 induced oxidative stress in human lens epithelial B3 (HLE-B3) cell
      lines and investigate their relations with the progression of age-related nuclear
      cataract. METHODS: H2O2 was used to induce oxidative stress in HLE-B3 cells. A
      genome-wide expression profiling of miRNAs in HLE-B3 cells was performed to
      select the differentially expressed miRNAs before and after H2O2 treatment. The
      selected miRNAs were validated by RT-PCR and fluorescence in situ hybridization
      (FISH). Clinical specimens were divided into three groups according to the Lens
      Opacities Classification System III (LOCSIII) and the expression levels of the
      selected miRNAs were tested by RT-PCR in the three groups. Bioinformatics
      analyses were applied to predict the target genes of the miRNA hits and construct
      the miRNA regulatory network. The expression level of MAPK14 was analyzed by
      Western blot. RESULTS: The H2O2 induced oxidative stress model of HLE-B3 cells
      was established. Nineteen upregulated and 30 downregulated miRNAs were identified
      as differentially expressed miRNAs. Seven of the total 49 were validated in the
      cell model. RT-PCR of the clinical samples showed that the expression levels of
      miR-34a-5p, miR-630 and miR-335-3p were closely related with the severity of
      nuclear opacity. The images taken from FISH confirmed the results of RT-PCR.
      There were 172 target genes of the three miRNAs clustered in the category of
      response to stress. The regulatory network demonstrated that 23 target genes were
      co-regulated by multiple miRNAs. MAPK14 was the target gene of three miRNAs and
      the result were verified by Western blot. CONCLUSION: Up-regulation of miR-34a-5p
      and miR-630 and down-regulation of miR-335-3p are related with the progression of
      age-related nuclear cataract and the underlying mechanism awaits further
      functional research to reveal.

PMID- 29653566
TI  - The association between minor recurrent aphthous stomatitis (RAS), children's
      poor oral condition, and underlying negative psychosocial habits and attitudes
      towards oral hygiene.
AB  - BACKGROUND: Minor Recurrent Aphthous Stomatitis (RAS) represents a disease which
      is very difficult to prevent. This case-control study focused on possible
      associations between minor Recurrent Aphthous Stomatitis in children, their oral
      health, and underlying behavioral indexes of children's attitudes and habits
      pertaining to (home) oral hygiene, with the further goal of enabling the dentist
      to prevent these specific kind of lesions, both from a clinical and a broader
      psychosocial perspective. METHODS: Four hundred one school-children (5-10 years
      old) in Milan (Italy) were submitted to an intra-oral examination, and
      interviewed with the aid of a brief psychosocial questionnaire. RESULTS: At the
      clinical level, statistically significant associations were observed between the
      presence of decayed teeth and minor Recurrent Aphthous Stomatitis (Odds Ratio:
      3.15; 95% CI: lower limit 1.06; upper limit: 9.36; Z-test: 2.07, p = 0.039; Chi
      square = 4.71, p = 0.030), and between the Decayed Missing or Filled Teeth (DMFT)
      index and minor aphthous stomatitis (Odds Ratio: 3.30; 95% CI: lower limit 1.13;
      upper limit: 9.67; Z-test = 2.18, p = 0.029; Chi-square = 5.27; p = 0.022), both
      results pointing to a significant increase-by circa 3 times-in the risk of
      developing minor Recurrent Aphthous Stomatitis in children exposed to the two
      above-identified factors (i.e., the presence of decayed teeth and a clearly
      compromised oral condition, as signaled by the DMFT index), if compared with the
      risk run by their non-exposed counterparts. At the psychosocial level of
      analysis, statistically significant associations were observed (1) between
      children's practice of spontaneously brushing teeth when not at home and a
      comparatively lower (i.e. better) Decayed Missing or Filled Teeth index (Chi
      square: 8.95; p = 0.011), and (2) between receiving parental aid (e.g., proper
      brushing instructions) while practicing home oral hygiene and a significantly
      reduced presence of decayed teeth (Chi-square = 5.40; p = .067; Spearman's Rho, p
      = .038). Further, significant associations were also observed between children's
      reported severity of dental pain and both (a) the presence of decayed teeth (Chi
      square = 10.80; p = 0.011), and (b) children's (poor) oral health condition as
      expressed by the Decayed Missing or Filled Teeth index (Chi-square = 6.29; p =
      0.043). Interestingly, specific lifestyles and social status, showed no
      systematic association to other clinical or psychological/psychosocial indices.
      CONCLUSIONS: These systematic relations suggest that, in the presence of
      Recurrent Aphthous Stomatitis in pediatric patients, the dentist should carefully
      monitor children for potential carious lesions, implement protocols of prevention
      to control Recurrent Aphthous Stomatitis disease in children affected by caries,
      and also be particularly aware of the right or wrong habits children may acquire
      in the course of continued social exchange with their caregivers and peers.

PMID- 29653567
TI  - Population-level distribution and putative immunogenicity of cancer neoepitopes.
AB  - BACKGROUND: Tumor neoantigens are drivers of cancer immunotherapy response;
      however, current prediction tools produce many candidates requiring further
      prioritization. Additional filtration criteria and population-level understanding
      may assist with prioritization. Herein, we show neoepitope immunogenicity is
      related to measures of peptide novelty and report population-level behavior of
      these and other metrics. METHODS: We propose four peptide novelty metrics to
      refine predicted neoantigenicity: tumor vs. paired normal peptide binding
      affinity difference, tumor vs. paired normal peptide sequence similarity, tumor
      vs. closest human peptide sequence similarity, and tumor vs. closest microbial
      peptide sequence similarity. We apply these metrics to neoepitopes predicted from
      somatic missense mutations in The Cancer Genome Atlas (TCGA) and a cohort of
      melanoma patients, and to a group of peptides with neoepitope-specific immune
      response data using an extension of pVAC-Seq (Hundal et al., pVAC-Seq: a genome
      guided in silico approach to identifying tumor neoantigens. Genome Med 8:11,
      2016). RESULTS: We show neoepitope burden varies across TCGA diseases and HLA
      alleles, with surprisingly low repetition of neoepitope sequences across patients
      or neoepitope preferences among sets of HLA alleles. Only 20.3% of predicted
      neoepitopes across TCGA patients displayed novel binding change based on our
      binding affinity difference criteria. Similarity of amino acid sequence was
      typically high between paired tumor-normal epitopes, but in 24.6% of cases,
      neoepitopes were more similar to other human peptides, or bacterial (56.8% of
      cases) or viral peptides (15.5% of cases), than their paired normal counterparts.
      Applied to peptides with neoepitope-specific immune response, a linear model
      incorporating neoepitope binding affinity, protein sequence similarity between
      neoepitopes and their closest viral peptides, and paired binding affinity
      difference was able to predict immunogenicity (AUROC = 0.66). CONCLUSIONS: Our
      proposed prioritization criteria emphasize neoepitope novelty and refine patient
      neoepitope predictions for focus on biologically meaningful candidate
      neoantigens. We have demonstrated that neoepitopes should be considered not only
      with respect to their paired normal epitope, but to the entire human proteome,
      and bacterial and viral peptides, with potential implications for neoepitope
      immunogenicity and personalized vaccines for cancer treatment. We conclude that
      putative neoantigens are highly variable across individuals as a function of
      cancer genetics and personalized HLA repertoire, while the overall behavior of
      filtration criteria reflects predictable patterns.

PMID- 29653568
TI  - Prevalence and intensity of catastrophic health care expenditures in Iran from
      2008 to 2015: a study on Iranian household income and expenditure survey.
AB  - BACKGROUND: Households exposure to catastrophic health expenditure is a valuable
      measure to monitor financial protection in health sector payments. The present
      study had two aims: first, to estimate the prevalence and intensity of
      catastrophic health expenditures (CHE) in Iran. Second, to investigate main
      factors that influence the probability of CHE. METHODS: CHE is defined as an
      occasion in which a household's out-of-pocket (OOP) spending exceeds 40% of the
      total income that remains after subtraction of living expenses. This study used
      the data from eight national repeated cross-sectional surveys on households'
      income and expenditure. The proportion of households facing CHE, as a prevalence
      measure, was estimated for rural and urban areas. The intensity of CHE was also
      calculated using overshoot and mean positive overshoot (MPO) measures. The
      factors affecting the CHE were also analyzed using logistic random effects
      regression model. We also used ArcMap 10.1 to display visually disparities across
      the country. RESULTS: An increasing number of Iranians has been subject to
      catastrophic health care costs over the study period in both rural and urban
      areas (CHE = 2.57% in 2008 and 3.25% in 2015). In the same period, the overshoot
      of CHE and the mean positive overshoot ranged from 0.26% to 0.65% and from 12.26%
      to 20.86%, respectively. The average absolute monetary value of OOP spending per
      month has been low in rural areas over the years, but the prevalence of CHE has
      been higher than urban areas. Generally put, rural settlement, higher income,
      receiving inpatient and outpatient services, and existence of elderly people in
      the household led to increase in CHE prevalence (p < 0.05). Interestingly,
      provinces with more limited geographical and cultural accessibility had the
      lowest CHE. CONCLUSIONS: According to the findings, Iran's healthcare system has
      failed to realize the aim of five-year national development plan regarding CHE
      prevalence (1% CHE prevalence according to the plan). Therefore, revision of
      financial health care protection policies focusing on pre-payments seems
      mandatory. For instance, these policies should extend the interventions that
      target low-income populations particularly in rural areas, provide more coverage
      for catastrophic medical services in basic benefit packages, and develop
      supplementary health insurance.

PMID- 29653569
TI  - ACUDIN - ACUpuncture and laser acupuncture for treatment of DIabetic peripheral
      Neuropathy: a randomized, placebo-controlled, partially double-blinded trial.
AB  - BACKGROUND: Diabetic peripheral neuropathy (DPN) is the most common complication
      of diabetes mellitus with significant clinical sequelae that can affect a
      patient's quality of life. Metabolic and microvascular factors are responsible
      for nerve damage, causing loss of nerve function, numbness, painful sensory
      symptoms, and muscle weakness. Therapy is limited to anti-convulsant or anti
      depressant drugs for neuropathic pain and paresthesia. However, reduced
      sensation, balance and gait problems are insufficiently covered by this
      treatment. Previous data suggests that acupuncture, which has been in use in
      Traditional Chinese Medicine for many years, may potentially complement the
      treatment options for peripheral neuropathy. Nevertheless, more objective data on
      clinical outcome is necessary to generally recommend acupuncture to the public.
      METHODS: We developed a study design for a prospective, randomized (RCT), placebo
      controlled, partially double-blinded trial for investigating the effect of
      acupuncture on DPN as determined by nerve conduction studies (NCS) with the sural
      sensory nerve action potential amplitude as the primary outcome. The sural
      sensory nerve conduction velocity, tibial motor nerve action potential amplitude,
      tibial motor nerve conduction velocity, the neuropathy deficit score, neuropathy
      symptom score, and numeric rating scale questionnaires are defined as secondary
      outcomes. One hundred and eighty patients with type 2 diabetes mellitus will be
      randomized into three groups (needle acupuncture, verum laser acupuncture, and
      placebo laser acupuncture). We hypothesize that needle and laser acupuncture have
      beneficial effects on electrophysiological parameters and clinical and subjective
      symptoms in relation to DPN in comparison with placebo. DISCUSSION: The ACUDIN
      trial aims at investigating whether classical needle acupuncture and/or laser
      acupuncture are efficacious in the treatment of DPN. For the purpose of an
      objective parameter, NCS were chosen as outcome measures. Acupuncture treatment
      may potentially improve patients' quality of life and reduce the socio-economic
      burden caused by DPN. TRIAL REGISTRATION: German Clinical Trial Register (DRKS),
      No. DRKS00008562 , trial search portal of the WHO (
      http://apps.who.int/trialsearch/ ).

PMID- 29653570
TI  - Susceptibility to short-term ozone exposure and cardiovascular and respiratory
      mortality by previous hospitalizations.
AB  - BACKGROUND: Ozone (O3) has been associated with cardiorespiratory mortality
      although few studies have explored susceptible populations based on prior
      disease. We aimed to investigate the role of previous hospitalization on the
      association between short-term exposure to O3 and cardiovascular (CV) and
      respiratory mortality. METHODS: We performed time series analyses using
      generalized additive models and case-crossover on 136,624 CV and 23,281
      respiratory deaths in Stockholm County (1990-2010). Deaths were linked to
      hospital admissions data. We constructed 2-day and 7-day averages using daily 8-h
      maximum for O3 and hourly values for PM2.5, PM10, NO2, and NOx from a fixed
      monitor. RESULTS: We observed a 0.7% (95% CI: 0.1%, 1.3%) and 2.7% (95% CI: 0.8%,
      4.6%) higher risk of CV and respiratory death per 10 MUg/m3 higher 2-day and 7
      day average O3 respectively. Individuals previously hospitalized for myocardial
      infarction demonstrated 1.8% (95% CI: 0.4%, 3.4%) higher risk of CV death per 10
      MUg/m3 higher 2-day average O3 and similar associations were observed in
      individuals with no previous hospitalization for any cause. Individuals with
      previous hospitalizations did not show susceptibility towards O3-related risk of
      respiratory mortality. We observed no associations for other pollutants.
      CONCLUSION: Short-term ozone exposure is associated with CV and respiratory
      mortality and our results may suggest higher susceptibility to CV mortality
      following O3 exposure in individuals previously hospitalized for myocardial
      infarction. Higher risks were also observed in individuals with cardiovascular
      death as their first presentation of disease.

PMID- 29653571
TI  - Why ethnicity and gender matters for fertility intention among married young
      people: a baseline evaluation from a gender transformative intervention in rural
      India.
AB  - BACKGROUND: Social inequities in early child bearing persist among young married
      people, especially among tribal populations in India. Rural women belonging to
      tribal groups and those coming from poor households are more likely to give birth
      before age 18. This paper explores the connection between ethnicity, gender and
      early fertility intention among young married people in rural India. METHODS: The
      data is drawn from a cross sectional baseline evaluation of an intervention
      programme in rural India. A sample of 273 married young people was taken.
      Respondents were selected using systematic random sampling. Logistic Regression
      was used to assess the effect of being a tribal on early fertility intention and
      also to determine if covariates associated with early fertility intention
      differed by tribal status. Qualitative data was analysed using deductive content
      analysis approach. RESULTS: Bivariate and logistic regression results indicated
      that young married people from tribal communities had higher odds of planning a
      child within one year of marriage than non-tribals (OR = 1.47, p-value-0.079).
      Findings further suggest that early fertility intention among tribals is driven
      by gender factors and higher education and among non-tribals, higher education
      and awareness on contraception are key predictors. Among tribals, the odds of
      planning a child within one year of marriage was strongly associated with
      inequitable gender norms (OR = 1.94, p-value-0.002). Higher education showed
      significant positive association with non-tribals (OR = 0.19, p-value-0.014) and
      positive association with tribals (OR = 0.56, p-value-0.416). Qualitative
      investigation confirms that fertility desires of young married people are
      strongly influenced by gender norms especially among tribal populations.
      CONCLUSION: Early child bearing was underpinned by complex ethnic factors and
      gender norms. Preference for early child bearing was seen most among tribal
      communities. Gender attitudes were a cause of concern especially among tribal
      groups. These results suggest that efforts to improve early child birth will
      require changing gender norms related to fertility among tribals as well as
      social equity issues including higher education among non-tribals and tribals.

PMID- 29653572
TI  - Impact of parents' need for care on middle-aged women's lifestyle and
      psychological distress: evidence from a nationwide longitudinal survey in Japan.
AB  - BACKGROUND: Many studies have separately addressed the associations of informal
      caregiving with coresidence, a caregiver's work status, and health conditions,
      but not jointly. We examined how their parents' need for care affects middle-aged
      women's lifestyle and psychological distress, considering the potential
      simultaneity of decisions on caregiving and living adjustments. METHODS: We used
      22,305 observations of 7037 female participants (aged 54-67 years) from a
      nationwide longitudinal survey in Japan conducted during 2009 and 2013. We
      considered the occurrence of parents' need for care (OPNC) as an external event
      and estimated regression models to explain how it affected the probabilities of
      the participants becoming caregivers, coresiding with parents, and working
      outside the home. We further conducted the mediation analysis to examine how the
      impact of OPNC on participants' psychological distress measured by Kessler 6 (K6)
      scores was mediated by caregiving and living adjustments. RESULTS: OPNC made
      30.9% and 30.3% of middle-aged women begin informal caregiving for parents and
      parents-in-law, respectively, whereas the impact on residential arrangement with
      parents or work status was non-significant or rather limited. OPNC raised middle
      aged women' K6 scores (range: 0-24) by 0.368 (SE: 0.061) and 0.465 (SE: 0.073)
      for parents and parents-in-law, respectively, and informal caregiving mediated
      those impacts by 37.7% (95% CI: 15.6-68.2%) and 44.0% (95% CI: 22.2-75.4%),
      respectively. By contrast, the mediating effect of residential arrangement with
      parents or work status was non-significant. CONCLUSIONS: Results underscore the
      fact that OPNC tends to promote middle-aged women to begin informal caregiving
      and worsen their psychological distress.

PMID- 29653573
TI  - A systematic review of non-antibiotic measures for the prevention of urinary
      tract infections in pregnancy.
AB  - BACKGROUND: Urinary tract infections (UTIs) are common in pregnancy and account
      for the highest proportion of primary care antibiotic prescriptions issued to
      pregnant women in the UK. It is well known that antibiotic use is associated with
      increased antimicrobial resistance and therefore measures to minimise antibiotic
      use for UTI prevention have been studied. The efficacy and safety of these
      measures in pregnancy have not been addressed and therefore the aim of this study
      was to systematically review the literature to identify and evaluate potential
      measures to prevent UTIs in pregnant women. METHODS: Ten databases (EMBASE, AMED,
      BNI, CINAHL, Medline, PubMed, PsycINFO, Cochrane Trials, Scopus and Science
      Direct) were systematically searched in July 2017 for studies reporting non
      antibiotic measures to prevent UTIs in pregnancy. The terms ("urinary tract
      infection" or UTI or bacteriuria or cystitis) AND (prevention) AND (pregnan*)
      were used. The quality of the publications was appraised using the Critical
      Appraisal Skills Programme (CASP) checklists for cohort study, case-control study
      and randomised controlled trial. The results were synthesised using a textual
      narrative approach. RESULTS: Search results yielded 3276 publications and after
      reviewing titles and removing duplicates, 57 full text articles were assessed for
      eligibility and eight were included in the review. Five different approaches
      (hygiene measures, cranberry juice, immunisation, ascorbic acid and Canephron(r)
      N) have been identified, all of which are reported to be safe in pregnancy.
      CONCLUSION: The quality of the evidence varied considerably and only hygiene
      measures were supported by evidence to be recommended in practice. Future work
      needs to concentrate on strengthening the evidence base through improved design
      and reporting of studies with a focus on immunisation, ascorbic acid and
      Canephron(r) N.

PMID- 29653574
TI  - Primary sarcomatoid urothelial carcinoma of the ureter: a case report and review
      of the literature.
AB  - BACKGROUND: Sarcomatoid urothelial carcinoma is a very dangerous malignant tumour
      derived from the epithelium. Primary sarcomatoid carcinoma of the ureter is
      extremely rare in clinical practice. The prognosis of this kind of disease is
      really poor, and there is still not a diagnosis standard in the world. CASE
      PRESENTATION: An 82-year-old female patient who had intermittent waist pain
      without any other symptoms, had diagnosed as urothelial cancer on computerised
      tomography urography. Considering the patient's age and quality of life, we made
      a preserving kidneys resection of the local tumour. The tumour was composed of
      sarcomatous and carcinomatous elements, and immunohistochemical examination
      showed that tumour cells were positive for cytokeratin, epithelial membrane
      antigen, vimentin, and GATA3 markers. There were no complications after 1-hour
      surgery. After 3 months, there was no signs of recurrence and metastasis.
      CONCLUSION: This case was a patient with sacomatoid urothelial carcinoma. Through
      a transurethral resection with laser, the patient recovered well, and there was
      no sign of any recurrence of the tumour after 3 months. With the development of
      technology and science, more and more cancerous patients' living quality and
      survival rate were improved. Maybe it is essential for urologists and scientists
      to entirely understand the characteristics of the sarcomatoid urothelial
      carcinoma and make a better clinical guideline.

PMID- 29653575
TI  - Enhanced stability of a chimeric hepatitis B core antigen virus-like-particle
      (HBcAg-VLP) by a C-terminal linker-hexahistidine-peptide.
AB  - BACKGROUND: Virus-like-particles (VLPs) are attractive nanoparticulate scaffolds
      for broad applications in material/biological sciences and medicine. Prior their
      functionalization, specific adaptations have to be carried out. These adjustments
      frequently lead to disordered particles, but the particle integrity is an
      essential factor for the VLP suitability. Therefore, major requirements for
      particle stabilization exist. The objective of this study was to evaluate novel
      stabilizing elements for functionalized chimeric hepatitis B virus core antigen
      virus-like particles (HBcAg-VLP), with beneficial characteristics for vaccine
      development, imaging or delivery. RESULTS: The effects of a carboxy-terminal
      polyhistidine-peptide and an intradimer disulfide-bridge on the stability of
      preclinically approved chimeric HBcAg-VLPs were assessed. We purified recombinant
      chimeric HBcAg-VLPs bearing different modified C-termini and compared their
      physical and chemical particle stability by quantitative protein-biochemical and
      biophysical techniques. We observed lower chemical resistance of T = 3- compared
      to T = 4-VLP (triangulation number) capsids and profound impairment of
      accessibility of hexahistidine-peptides in assembled VLPs. Histidines attached to
      the C-terminus were associated with superior mechanical and/or chemical particle
      stability depending on the number of histidine moieties. A molecular modeling
      approach based on cryo-electron microscopy and biolayer interferometry revealed
      the underlying structural mechanism for the strengthening of the integrity of
      VLPs. Interactions triggering capsid stabilization occur on a highly conserved
      residue on the basis of HBcAg-monomers as well as on hexahistidine-peptides of
      adjacent monomers. This new stabilization mechanism appears to mimic an
      evolutionary conserved stabilization concept for hepadnavirus core proteins.
      CONCLUSIONS: These findings establish the genetically simply transferable C
      terminal polyhistidine-peptide as a general stabilizing element for chimeric
      HBcAg-VLPs to increase their suitability.

PMID- 29653576
TI  - Meningeal carcinomatosis: three case-reports.
AB  - BACKGROUND: Meningeal carcinomatosis (MC) is characterized by diffuse
      infiltration of tumor cells in meninges. There is no tumor mass in the brain and
      parenchyma of the spinal cord. MC is divided into primary and metastatic types.
      MC cases were previously diagnosed postoperatively or at autopsy. Recent advances
      in spinal abbreviation cytology and imaging have led to increase in number of
      reported cases. In this study, we discuss the manifestations of MC patients based
      on magnetic resonance imaging (MRI) findings, as well as the correlation between
      the manifestations and pathology. CASE PRESENTATION: MC was confirmed in all
      three cases by lumbar puncture and gadopentetate dimeglumine-enhanced magnetic
      resonance imaging. Due to different primary diseases, the patients had specific
      imaging manifestations. CONCLUSION: Enhanced MRI examination is extremely
      sensitive for detecting abnormalities in meninges, which plays a very important
      role in the diagnosis of MC. Since meninges of some MC patients cannot be
      enhanced, the enhanced MRI examination cannot be replaced by conventional
      cerebrospinal abbreviation examination. Attribute to the diversity of MR contrast
      agents, which could provide higher lesion conspicuity and enhances lesion
      detection, there may be some more choices to improve the detection rate of MC
      patients and prolong their survival lifetime.

PMID- 29653578
TI  - Electronic cigarette use in Greece: an analysis of a representative population
      sample in Attica prefecture.
AB  - BACKGROUND: The purpose was to assess prevalence and correlates of electronic
      cigarette (e-cigarette) use in Greece in 2017. METHODS: A cross-sectional survey
      of a representative sample of 4058 adults living in Attica prefecture (35% of the
      Greek adult population) was performed in May 2017 through telephone interviews.
      Prevalence and frequency of e-cigarette use were assessed according to the
      smoking status, and logistic regression analysis was performed to identify
      correlates of use. RESULTS: Current smoking was reported by 32.6% of
      participants. Ever e-cigarette use was reported by 54.1% (51.4-56.8%) of current
      smokers, 24.1% (21.7-26.5%) of former smokers and 6.5% (5.3-7.7%) of never
      smokers. Past experimentation was the most prevalent pattern of e-cigarette use
      among ever users (P < 0.001). Almost 80% of ever and 90% of current e-cigarette
      users were using nicotine. Extrapolated to the whole Attica population (3.1
      million), there were 1 million current smokers, 848,000 ever e-cigarette users
      and 155,000 current e-cigarette users. The majority of current e-cigarette users
      (62.2%) were former smokers. Only 0.2% of never smokers were current e-cigarette
      users. One out of 20 participants considered e-cigarettes a lot less harmful than
      smoking. Being current or former smoker were the strongest correlates current e
      cigarette use (OR 30.82, 95%CI 10. 21-69.33 and OR 69.33, 95%CI 23.12-207.90
      respectively). CONCLUSIONS: E-cigarette use in Greece is largely confined to
      current or former smokers, while current use and nicotine use by never smokers is
      extremely rare. The majority of current e-cigarette users were former smokers.
      Most participants overestimate the harmfulness of e-cigarettes relative to
      smoking.

PMID- 29653577
TI  - Nanotechnology based approaches for detection and delivery of microRNA in
      healthcare and crop protection.
AB  - Nanobiotechnology has the potential to revolutionize diverse sectors including
      medicine, agriculture, food, textile and pharmaceuticals. Disease diagnostics,
      therapeutics and crop protection strategies are fast emerging using nanomaterials
      preferably nanobiomaterials. It has potential for development of novel
      nanobiomolecules which offer several advantages over conventional treatment
      methods. RNA nanoparticles with many unique features are promising candidates in
      disease treatment. The miRNAs are involved in many biochemical and developmental
      pathways and their regulation in plants and animals. These appear to be a
      powerful tool for controlling various pathological diseases in human, plants and
      animals, however there are challenges associated with miRNA based nanotechnology.
      Several advancements made in the field of miRNA therapeutics make it an
      attractive approach, but a lot more has to be explored in nanotechnology assisted
      miRNA therapy. The miRNA based technologies can be employed for detection and
      combating crop diseases as well. Despite these potential advantages,
      nanobiotechnology applications in the agricultural sector are still in its
      infancy and have not yet made its mark in comparison with healthcare sector. The
      review provides a platform to discuss nature, role and use of miRNAs in
      nanobiotechnology applications.

PMID- 29653580
TI  - The effect of a portion size intervention on French fries consumption, plate
      waste, satiety and compensatory caloric intake: an on-campus restaurant
      experiment.
AB  - BACKGROUND: One of the driving factors of dietary overconsumption throughout the
      last decennia is the increase of food portion sizes. Larger portions induce
      higher daily energy intake, so reducing portion size may reduce intake of excess
      calories. However, real-life studies about the effects of portion size reduction
      are lacking. Therefore, this study examined the effect of a French fries portion
      size reduction on French fries consumption, French fries plate waste, satiety and
      caloric intake during the subsequent afternoon among university students and
      employees in a Belgian on-campus restaurant setting. Moreover, this study
      evaluated consumers' perception about the portion size reduction. METHODS: The
      study took place over a two-time (i.e. baseline and intervention week) 4-day
      period (Tuesday-Friday) in the on-campus restaurant where +/-1200 meals are
      served every day. French fries' portions were reduced by 20% by replacing the
      usual porcelain bowl served during the baseline week (+/-200 g) with smaller
      volume paper bags during the intervention week (+/-159 g) in a pre-post real-life
      experiment. French fries consumption and plate waste were measured in 2056
      consumers at baseline and 2175 consumers at intervention. Additionally,
      interviews were conducted directly after lunch and again between 4 and 6 p.m. on
      the same day to assess satiety and caloric intake at pre and post in a small
      subsample of both French fries consumers (n = 19) and non-French fries consumers
      (n = 14). Post-intervention, the same subsample was interviewed about their
      perception of the portion size reduction (n = 28). RESULTS: Total French fries
      intake decreased by 9.1%, and total plate waste decreased by 66.4%. No
      differences were found in satiety or caloric intake between baseline and
      intervention week among the French fries' consumers. The majority (n = 24, 86%)
      of French fries consumers noticed the reduction in portion size during the
      intervention. Although most participants (n = 19, 68%) perceived the reduced
      portion size as sufficient, only a minority of participants (n = 9, 32%)
      indicated post-intervention that they would agree with a permanent
      implementation. CONCLUSIONS: Reducing portion size may lead to reduced caloric
      intake, without changing perceived levels of satiety.

PMID- 29653579
TI  - Delivery of siRNA in vitro and in vivo using PEI-capped porous silicon
      nanoparticles to silence MRP1 and inhibit proliferation in glioblastoma.
AB  - BACKGROUND: Multidrug resistance-associated protein 1 (MRP1) overexpression plays
      a major role in chemoresistance in glioblastoma multiforme (GBM) contributing to
      its notorious deadly nature. Although MRP1-siRNA transfection to GBM in vitro has
      been shown to sensitise the cells to drug, MRP1 silencing in vivo and the
      phenotypic influence on the tumour and normal tissues upon MRP1 down-regulation
      have not been established. Here, porous silicon nanoparticles (pSiNPs) that
      enable high-capacity loading and delivery of siRNA are applied in vitro and in
      vivo. RESULT: We established pSiNPs with polyethyleneimine (PEI) capping that
      enables high-capacity loading of siRNA (92 ug of siRNA/mg PEI-pSiNPs), and
      optimised release profile (70% released between 24 and 48 h). These pSiNPs are
      biocompatible, and demonstrate cellular uptake and effective knockdown of MRP1
      expression in GBM by 30%. Also, siRNA delivery was found to significantly reduce
      GBM proliferation as an associated effect. This effect is likely mediated by the
      attenuation of MRP1 transmembrane transport, followed by cell cycle arrest. MRP1
      silencing in GBM tumour using MRP1-siRNA loaded pSiNPs was demonstrated in mice
      (82% reduction at the protein level 48 h post-injection), and it also produced
      antiproliferative effect in GBM by reducing the population of proliferative
      cells. These results indicate that in vitro observations are translatable in
      vivo. No histopathological signs of acute damage were observed in other MRP1
      expressing organs despite collateral downregulations. CONCLUSIONS: This study
      proposes the potential of efficient MRP1-siRNA delivery by using PEI-capped
      pSiNPs in achieving a dual therapeutic role of directly attenuating the growth of
      GBM while sensitising residual tumour cells to the effects of chemotherapy post
      resection.

PMID- 29653581
TI  - Where we should focus? Myths and misconceptions of long acting contraceptives in
      southern nations, nationalities and People's region, Ethiopia: qualitative study.
AB  - BACKGROUND: Despite its wider benefits and access made at community level,
      contraceptive methods are one of underutilized services in study area and it is
      believed to be influenced by misconceptions and socio cultural values. This study
      was designed to explore women's perceptions, myths and misconception to inform
      program implementers. METHODS: Study was conducted in Southern Nations,
      Nationalities and People's Region, Ethiopia in 2015. Five focus group discussions
      with 50 women of reproductive age and 10 key informant interviews with providers
      and program officers were done. The discussions and interviews were tape
      recorded, transcribed verbatim and analyzed manually using framework analysis
      with deductive and descriptive approaches. RESULTS: Improving community awareness
      about contraceptives and benefits of contraceptive utilization were acknowledged
      by majority of participants. Long acting methods were less preferred due to
      perceived side effects, myths and misconceptions and desire to have more
      children. Additionally, socio-economic status and partner influence were listed
      as reason for non-use. Poor provider-client interaction on available methods was
      also reported as system related gap. CONCLUSION: Program implementers need to
      address fears, myths and misconceptions. Quality of family planning counselling
      should be monitored.

PMID- 29653582
TI  - MBL2 gene polymorphism rs1800450 and rheumatic fever with and without rheumatic
      heart disease: an Egyptian pilot study.
AB  - BACKGROUND: Rheumatic fever (RF) is the result of an autoimmune response to
      pharyngitis caused by infection with Streptococcus pyogenes. RF is most prevalent
      in Africa and the Middle East. Rheumatic heart disease (RHD) is the most serious
      complication of RF. Mannose-binding lectin 2 gene (MBL2) has been reported to be
      correlated with different cardiac conditions. In Egyptian patients as a new
      studied ethnic population, it is the first time to evaluate the association
      between MBL2 gene polymorphism rs1800450 and RF with and without RHD. METHODS:
      One hundred and sixty RF patients (80 with RHD and 80 without RHD) and eighty
      healthy ethnically matched controls were studied. MBL2 (rs1800450) was genotyped
      by real-time PCR using TaqMan(r) allele discrimination assay. The MBL level was
      measured by ELISA. Westergren erythrocytes sedimentation rate (ESR), anti
      streptolysin O titer (ASOT), C-reactive protein (CRP) and complements (C3 and C4)
      were determined. RESULTS: The AA genotype with high production of MBL was
      associated with increased risk of RHD more than the B allele carrying subjects.
      However, MBL2 genotype related to the low production of MBL was more frequently
      observed in those patients without RHD. CONCLUSIONS: Our results suggested the
      involvement of MBL2 (rs1800450) polymorphism and its protein in RHD pathogenesis.
      Also, it might be a promising future strategy to utilize this polymorphism to
      help differentiate patients with RHD from those without RHD.

PMID- 29653583
TI  - New additions to the cancer precision medicine toolkit.
AB  - New computational and database-driven tools are emerging to aid in the
      interpretation of cancer genomic data as its use becomes more common in clinical
      evidence-based cancer medicine. Two such open source tools, published recently in
      Genome Medicine, provide important advances to address the clinical cancer
      genomics data interpretation bottleneck.

PMID- 29653585
TI  - Most-enhancing tumor volume by MRI radiomics predicts recurrence-free survival
      "early on" in neoadjuvant treatment of breast cancer.
AB  - BACKGROUND: The hypothesis of this study was that MRI-based radiomics has the
      ability to predict recurrence-free survival "early on" in breast cancer
      neoadjuvant chemotherapy. METHODS: A subset, based on availability, of the ACRIN
      6657 dynamic contrast-enhanced MR images was used in which we analyzed images of
      all women imaged at pre-treatment baseline (141 women: 40 with a recurrence, 101
      without) and all those imaged after completion of the first cycle of
      chemotherapy, i.e., at early treatment (143 women: 37 with a recurrence vs. 105
      without). Our method was completely automated apart from manual localization of
      the approximate tumor center. The most enhancing tumor volume (METV) was
      automatically calculated for the pre-treatment and early treatment exams.
      Performance of METV in the task of predicting a recurrence was evaluated using
      ROC analysis. The association of recurrence-free survival with METV was assessed
      using a Cox regression model controlling for patient age, race, and hormone
      receptor status and evaluated by C-statistics. Kaplan-Meier analysis was used to
      estimate survival functions. RESULTS: The C-statistics for the association of
      METV with recurrence-free survival were 0.69 with 95% confidence interval of
      [0.58; 0.80] at pre-treatment and 0.72 [0.60; 0.84] at early treatment. The
      hazard ratios calculated from Kaplan-Meier curves were 2.28 [1.08; 4.61], 3.43
      [1.83; 6.75], and 4.81 [2.16; 10.72] for the lowest quartile, median quartile,
      and upper quartile cut-points for METV at early treatment, respectively.
      CONCLUSION: The performance of the automatically-calculated METV rivaled that of
      a semi-manual model described for the ACRIN 6657 study (published C-statistic
      0.72 [0.60; 0.84]), which involved the same dataset but required semi-manual
      delineation of the functional tumor volume (FTV) and knowledge of the pre
      surgical residual cancer burden.

PMID- 29653584
TI  - Exposure to the gut microbiota drives distinct methylome and transcriptome
      changes in intestinal epithelial cells during postnatal development.
AB  - BACKGROUND: The interplay of epigenetic processes and the intestinal microbiota
      may play an important role in intestinal development and homeostasis. Previous
      studies have established that the microbiota regulates a large proportion of the
      intestinal epithelial transcriptome in the adult host, but microbial effects on
      DNA methylation and gene expression during early postnatal development are still
      poorly understood. Here, we sought to investigate the microbial effects on DNA
      methylation and the transcriptome of intestinal epithelial cells (IECs) during
      postnatal development. METHODS: We collected IECs from the small intestine of
      each of five 1-, 4- and 12 to 16-week-old mice representing the infant, juvenile,
      and adult states, raised either in the presence or absence of a microbiota. The
      DNA methylation profile was determined using reduced representation bisulfite
      sequencing (RRBS) and the epithelial transcriptome by RNA sequencing using paired
      samples from each individual mouse to analyze the link between microbiota, gene
      expression, and DNA methylation. RESULTS: We found that microbiota-dependent and 
      independent processes act together to shape the postnatal development of the
      transcriptome and DNA methylation signatures of IECs. The bacterial effect on the
      transcriptome increased over time, whereas most microbiota-dependent DNA
      methylation differences were detected already early after birth. Microbiota
      responsive transcripts could be attributed to stage-specific cellular programs
      during postnatal development and regulated gene sets involved primarily immune
      pathways and metabolic processes. Integrated analysis of the methylome and
      transcriptome data identified 126 genomic loci at which coupled differential DNA
      methylation and RNA transcription were associated with the presence of intestinal
      microbiota. We validated a subset of differentially expressed and methylated
      genes in an independent mouse cohort, indicating the existence of microbiota
      dependent "functional" methylation sites which may impact on long-term gene
      expression signatures in IECs. CONCLUSIONS: Our study represents the first genome
      wide analysis of microbiota-mediated effects on maturation of DNA methylation
      signatures and the transcriptional program of IECs after birth. It indicates that
      the gut microbiota dynamically modulates large portions of the epithelial
      transcriptome during postnatal development, but targets only a subset of
      microbially responsive genes through their DNA methylation status.

PMID- 29653586
TI  - Sub-chronic toxicopathological study of lantadenes of Lantana camara weed in
      Guinea pigs.
AB  - BACKGROUND: In the field conditions, animals regularly consume small quantities
      of lantana leaves either while grazing or due to mixing with regular fodder. The
      hypothesis of this study was that consumption of lantana toxins over a long
      period of time leads to progression of sub-clinical disease. Toxicopathological
      effects of sub-chronic (90 days) administration of lantadenes of L. camara were
      investigated in guinea pigs. For this, a total of 40 animals were divided into 5
      groups whereby groups I, II, III and IV were orally administered lantadenes,
      daily at the dose of 24, 18, 12, and 6 mg/kg bw, respectively while group V was
      control. The animals were evaluated by weekly body weight changes, haematology,
      serum liver and kidney markers, tissue oxidative markers and histopathology.
      RESULTS: The results of significant decrease in weekly body weights, haematology,
      liver and kidney marker enzymes (alanine aminotransaminase, aspartate
      aminotransaminase, acid phosphatase and creatinine), oxidation stress markers
      (lipid peroxidation, reduced glutathione, superoxide dismutase and catalase) in
      liver and kidneys, histopathology, and confirmation of fibrous collagenous tissue
      proliferation by Masson's Trichome stain showed that lantadenes led to a dose
      dependent toxicity in decreasing order with the highest dose (24 mg/kg bw)
      producing maximum lesions and the lowest dose (6 mg/kg bw) producing minimum
      alterations. CONCLUSIONS: The study revealed that lantadenes which are considered
      to be classical hepatotoxicants in acute toxicity produced pronounced
      nephrotoxicity during sub-chronic exposure. Further studies are needed to
      quantify the levels of lantadenes in blood or serum of animals exposed to lantana
      in field conditions which would help to assess the extent of damage to the vital
      organs.

PMID- 29653587
TI  - Three-dimensional printed PLA scaffold and human gingival stem cell-derived
      extracellular vesicles: a new tool for bone defect repair.
AB  - BACKGROUND: The role of bone tissue engineering in the field of regenerative
      medicine has been a main research topic over the past few years. There has been
      much interest in the use of three-dimensional (3D) engineered scaffolds (PLA)
      complexed with human gingival mesenchymal stem cells (hGMSCs) as a new
      therapeutic strategy to improve bone tissue regeneration. These devices can mimic
      a more favorable endogenous microenvironment for cells in vivo by providing 3D
      substrates which are able to support cell survival, proliferation and
      differentiation. The present study evaluated the in vitro and in vivo capability
      of bone defect regeneration of 3D PLA, hGMSCs, extracellular vesicles (EVs), or
      polyethyleneimine (PEI)-engineered EVs (PEI-EVs) in the following experimental
      groups: 3D-PLA, 3D-PLA + hGMSCs, 3D-PLA + EVs, 3D-PLA + EVs + hGMSCs, 3D-PLA +
      PEI-EVs, 3D-PLA + PEI-EVs + hGMSCs. METHODS: The structural parameters of the
      scaffold were evaluated using both scanning electron microscopy and
      nondestructive microcomputed tomography. Nanotopographic surface features were
      investigated by means of atomic force microscopy. Scaffolds showed a
      statistically significant mass loss along the 112-day evaluation. RESULTS: Our in
      vitro results revealed that both 3D-PLA + EVs + hGMSCs and 3D-PLA + PEI-EVs +
      hGMSCs showed no cytotoxicity. However, 3D-PLA + PEI-EVs + hGMSCs exhibited
      greater osteogenic inductivity as revealed by morphological evaluation and
      transcriptomic analysis performed by next-generation sequencing (NGS). In
      addition, in vivo results showed that 3D-PLA + PEI-EVs + hGMSCs and 3D-PLA + PEI
      EVs scaffolds implanted in rats subjected to cortical calvaria bone tissue damage
      were able to improve bone healing by showing better osteogenic properties. These
      results were supported also by computed tomography evaluation that revealed the
      repair of bone calvaria damage. CONCLUSION: The re-establishing of the integrity
      of the bone lesions could be a promising strategy in the treatment of accidental
      or surgery trauma, especially for cranial bones.

PMID- 29653588
TI  - The emerging role of fibrocytes in ocular disorders.
AB  - The fibrocyte, which was first described in 1994, is a type of circulating
      mesenchymal progenitor cell in the peripheral blood. Fibrocytes play important
      roles in chronic inflammation, wound healing, tissue remodeling, and fibrosis.
      Emerging evidence indicates that fibrocytes are involved in a wide variety of
      ocular disorders associated with inflammation and fibrosis. In this review, we
      summarize recent advances regarding the general characteristic profile of
      fibrocytes, molecular mechanisms underlying the fibrocyte recruitment to target
      tissues, their differentiation into fibroblasts, and the potential role of
      fibrocytes in ocular disease. Given the critical role of fibrocytes in ocular
      disorders, fibrocytes may serve as a promising pharmaceutical target in the
      development of novel therapeutic strategies to treat ocular inflammation and
      fibrosis.

PMID- 29653589
TI  - Histone H3K9 and H4 Acetylations and Transcription Facilitate the Initial CENP
      AHCP-3 Deposition and De Novo Centromere Establishment in Caenorhabditis elegans
      Artificial Chromosomes.
AB  - BACKGROUND: The centromere is the specialized chromatin region that directs
      chromosome segregation. The kinetochore assembles on the centromere, attaching
      chromosomes to microtubules in mitosis. The centromere position is usually
      maintained through cell cycles and generations. However, new centromeres, known
      as neocentromeres, can occasionally form on ectopic regions when the original
      centromere is inactivated or lost due to chromosomal rearrangements. Centromere
      repositioning can occur during evolution. Moreover, de novo centromeres can form
      on exogenously transformed DNA in human cells at a low frequency, which then
      segregates faithfully as human artificial chromosomes (HACs). How centromeres are
      maintained, inactivated and activated is unclear. A conserved histone H3 variant,
      CENP-A, epigenetically marks functional centromeres, interspersing with H3.
      Several histone modifications enriched at centromeres are required for centromere
      function, but their role in new centromere formation is less clear. Studying the
      mechanism of new centromere formation has been challenging because these events
      are difficult to detect immediately, requiring weeks for HAC selection. RESULTS:
      DNA injected into the Caenorhabditis elegans gonad can concatemerize to form
      artificial chromosomes (ACs) in embryos, which first undergo passive inheritance,
      but soon autonomously segregate within a few cell cycles, more rapidly and
      frequently than HACs. Using this in vivo model, we injected LacO repeats DNA,
      visualized ACs by expressing GFP::LacI, and monitored equal AC segregation in
      real time, which represents functional centromere formation. Histone H3K9 and H4
      acetylations are enriched on new ACs when compared to endogenous chromosomes. By
      fusing histone deacetylase HDA-1 to GFP::LacI, we tethered HDA-1 to ACs
      specifically, reducing AC histone acetylations, reducing AC equal segregation
      frequency, and reducing initial kinetochroe protein CENP-AHCP-3 and NDC-80
      deposition, indicating that histone acetylations facilitate efficient centromere
      establishment. Similarly, inhibition of RNA polymerase II-mediated transcription
      also delays initial CENP-AHCP-3 loading. CONCLUSIONS: Acetylated histones on
      chromatin and transcription can create an open chromatin environment, enhancing
      nucleosome disassembly and assembly, and potentially contribute to centromere
      establishment. Alternatively, acetylation of soluble H4 may stimulate the initial
      deposition of CENP-AHCP-3-H4 nucleosomes. Our findings shed light on the
      mechanism of de novo centromere activation.

PMID- 29653591
TI  - Is heavy eccentric calf training superior to wait-and-see, sham rehabilitation,
      traditional physiotherapy and other exercise interventions for pain and function
      in mid-portion Achilles tendinopathy?
AB  - BACKGROUND: Mid-portion Achilles tendinopathy (AT) is prevalent amongst athletic
      and non-athletic populations with pain, stiffness and impaired function typically
      reported. While different management options exist, loading protocols remain the
      best available intervention and have been shown to be effective in the management
      of AT. Trials investigating loading in AT have used a variety of different
      protocols, and recent narrative reviews suggest that no protocol is superior to
      another when comparing outcomes in pain and function. However, there has been no
      systematic review or meta-analysis completed to determine this. Furthermore, the
      narrative review did not consider wait-and-see or sham interventions, thus a
      systematic review and met-analysis which includes wait-and-see or sham
      interventions is warranted. METHODS: A systematic review and meta-analyses will
      be conducted as per the PRISMA guidelines. The databases PUBMED, CINAHL (Ovid)
      and CINAHL (EBSCO) will be searched for articles published from inception to 31
      December 2017. Our search focuses on studies examining the improvement of pain
      and function when completing a loading program for mid-portion AT. Only
      randomised/ quasi-randomised trials will be included while case reports and case
      series will be excluded. The primary outcome assessing pain and function will be
      the Victorian Institute Sports Assessment - Achilles (VISA-A). Two reviewers will
      screen articles, extract data and assess the risk of bias independently with a
      third reviewer resolving any disagreements between the two reviewers. A meta
      analysis will then be performed on the data (if appropriate) to determine if the
      traditional heavy load calf training protocol described by Alfredson is superior
      to wait-and-see, sham intervention, traditional physiotherapy, and other forms of
      exercise rehabilitation. DISCUSSION: This systematic review and meta-analysis
      will allow us to investigate if there are difference in pain and function when
      comparing wait-and-see, sham interventions, traditional physiotherapy and
      different exercise interventions to the traditional heavy eccentric calf training
      protocol for mid-portion Achilles tendon pain. SYSTEMATIC REVIEW REGISTRATION:
      PROSPERO registration number CRD42018084493 .

PMID- 29653590
TI  - Stem cell-derived mitochondria transplantation: a novel strategy and the
      challenges for the treatment of tissue injury.
AB  - Damage of mitochondria in the initial period of tissue injury aggravates the
      severity of injury. Restoration of mitochondria dysfunction and mitochondrial
      based therapeutics represent a potentially effective therapeutic strategy.
      Recently, mitochondrial transfer from stem cells has been demonstrated to play a
      significant role in rescuing injured tissues. The possible mechanisms of
      mitochondria released from stem cells, the pathways of mitochondria transfer
      between the donor stem cells and recipient cells, and the internalization of
      mitochondria into recipient cells are discussed. Moreover, a novel strategy for
      tissue injury based on the concept of stem cell-derived mitochondrial
      transplantation is pointed out, and the advantages and challenges are summarized.

PMID- 29653593
TI  - Wash-resistance of pirimiphos-methyl insecticide treatments of window screens and
      eave baffles for killing indoor-feeding malaria vector mosquitoes: an
      experimental hut trial, South East of Zambia.
AB  - BACKGROUND: The effectiveness of long-lasting insecticidal-treated nets (LLINs)
      and indoor residual spraying (IRS) for malaria control is threatened by
      resistance to commonly used pyrethroid insecticides. Rotations, mosaics,
      combinations, or mixtures of insecticides from different complementary classes
      are recommended by the World Health Organization (WHO) for mitigating against
      resistance, but many of the alternatives to pyrethroids are prohibitively
      expensive to apply in large national IRS campaigns. Recent evaluations of window
      screens and eave baffles (WSEBs) treated with pirimiphos-methyl (PM), to
      selectively target insecticides inside houses, demonstrated malaria vector
      mortality rates equivalent or superior to IRS. However, the durability of
      efficacy when co-applied with polyacrylate-binding agents (BA) remains to be
      established. This study evaluated whether WSEBs, co-treated with PM and BA have
      comparable wash resistance to LLINs and might therefore remain insecticidal for
      years rather than months. METHODS: WHO-recommended wire ball assays of
      insecticidal efficacy were applied to polyester netting treated with or without
      BA plus 1 or 2 g/sq m PM. They were then tested for insecticidal efficacy using
      fully susceptible insectary-reared Anopheles gambiae mosquitoes, following 0, 5,
      10, 15, then 20 washes as per WHO-recommended protocols for accelerated ageing of
      LLINs. This was followed by a small-scale field trial in experimental huts to
      measure malaria vector mortality achieved by polyester netting WSEBs treated with
      BA and 2 g/sq m PM after 0, 10 and then 20 standardized washes, alongside
      recently applied IRS using PM. RESULTS: Co-treatment with BA and either dosage of
      PM remained insecticidal over 20 washes in the laboratory. In experimental huts,
      WSEBs treated with PM plus BA consistently killed similar proportions of
      Anopheles arabiensis mosquitoes to PM-IRS (both consistently >= 94%), even after
      20 washes. CONCLUSION: Co-treating WSEBs with both PM and BA results in wash
      resistant insecticidal activity comparable with LLINs. Insecticide treatments for
      WSEBs may potentially last for years rather than months, therefore, reducing
      insecticide consumption by an order of magnitude relative to IRS. However,
      durability of WSEBs will still have to be assessed in real houses under
      representative field conditions of exposure to wear and tear, sunlight and rain.

PMID- 29653592
TI  - Amiodarone-induced reversible and irreversible hepatotoxicity: two case reports.
AB  - BACKGROUND: Amiodarone is a highly effective treatment for supraventricular and
      ventricular tachyarrhythmia; however, it could be associated with several serious
      adverse effects, including liver injury. CASE PRESENTATION: We report the
      clinical and histological features of two contrasting Japanese patients with
      amiodarone-induced reversible and irreversible hepatotoxicity. One patient with
      amiodarone-induced irreversible hepatotoxicity showed liver cirrhosis during
      treatment with amiodarone and died of hepatic failure; the other patient, who had
      reversible hepatotoxicity, showed a reversible course of liver function and
      imaging after discontinuation of amiodarone. CONCLUSIONS: We emphasize the
      importance of close monitoring of liver enzymes and evaluation of liver computed
      tomographic imaging as well as liver biopsy during treatment with amiodarone, and
      discontinuation should be considered when amiodarone-induced hepatotoxicity is
      suspected.

PMID- 29653594
TI  - Bronze Age meat industry: ancient mitochondrial DNA analyses of pig bones from
      the prehistoric salt mines of Hallstatt (Austria).
AB  - OBJECTIVE: In the Bronze Age Hallstatt metropolis ('Salzkammergut' region, Upper
      Austria), salt richness enabled the preservation of pork meat to sustain people's
      livelihood suggesting an organized meat production industry on a yearly basis of
      hundreds of pigs. To pattern the geographic and temporal framework of the early
      management of pig populations in the surrounding areas of Hallstatt, we want to
      gain insights into the phylogeographic network based on DNA sequence variation
      among modern pigs, wild boars and prehistoric (likely) domestic pigs. RESULTS: In
      this pilot study, we successfully adapted ancient DNA extraction and sequencing
      approaches for the analysis of mitochondrial DNA sequence variation in ten
      prehistoric porcine teeth specimens. Minimum-spanning network analyses revealed
      unique mitochondrial control region DNA haplotypes ranging within the variation
      of modern domestic pig and wild boar lineages and even shared haplotypes between
      prehistoric and modern domestic pigs and wild boars were observed.

PMID- 29653595
TI  - Public attitudes in Japan toward participation in whole genome sequencing
      studies.
AB  - BACKGROUND: Recent innovations in gene analysis technology have allowed for rapid
      and inexpensive sequencing of entire genomes. Thus, both conducting a study using
      whole genome sequencing (WGS) in a large population and the clinical application
      of research findings from such studies are currently feasible. However, to
      promote WGS studies, understanding and voluntary participation by the general
      public is needed. Therefore, it is essential to investigate the general public's
      attitude toward and understanding of WGS studies. The primary goal of our
      research is to investigate these issues and to discover how they relate to
      research participation in WGS studies. METHODS: A survey of awareness regarding
      WGS and studies using WGS was conducted with a sample of 2000 or more
      participants using a self-administered questionnaire posted on the Internet
      between February 20 and 21, 2015. Prior to the survey, we briefly explained WGS
      and WGS study-related issues to the respondents in order to provide them with the
      minimum knowledge required to answer the questionnaire. We then conducted an
      analysis, including cross-classification. RESULTS: For the question regarding
      interest in WGS, 46.6% of participants responded "Yes." 70.7% of all respondents
      said that they were interested in some kinds of findings that could be obtained
      from WGS studies. Regarding participation in WGS studies, 29.0% were interested
      in participating. The demographic factors significantly related to attitudes
      toward research participation were age, level of education, and employment
      status. The results also suggest that concerns about WGS have a positive effect
      on people's willingness to participate. Furthermore, it was shown that for people
      who were not interested in their gene-related information, concerns about WGS
      negatively impacted their willingness to participate. However, for people who
      were interested in their gene-related information, their concerns might not have
      impacted their willingness to participate. DISCUSSION AND CONCLUSIONS: This
      research has shown several key factors that affect the willingness of the general
      public for the participation to the WGS studies. One of the unexpected findings
      is that concerns toward WGS studies generally have positive effect on the
      peoples' attitude. It will be interesting to further investigate into the various
      types of concerns that people in different groups have about WGS.

PMID- 29653596
TI  - A meta-analysis of public microarray data identifies biological regulatory
      networks in Parkinson's disease.
AB  - BACKGROUND: Parkinson's disease (PD) is a long-term degenerative disease that is
      caused by environmental and genetic factors. The networks of genes and their
      regulators that control the progression and development of PD require further
      elucidation. METHODS: We examine common differentially expressed genes (DEGs)
      from several PD blood and substantia nigra (SN) microarray datasets by meta
      analysis. Further we screen the PD-specific genes from common DEGs using GCBI.
      Next, we used a series of bioinformatics software to analyze the miRNAs, lncRNAs
      and SNPs associated with the common PD-specific genes, and then identify the mTF
      miRNA-gene-gTF network. RESULT: Our results identified 36 common DEGs in PD blood
      studies and 17 common DEGs in PD SN studies, and five of the genes were
      previously known to be associated with PD. Further study of the regulatory miRNAs
      associated with the common PD-specific genes revealed 14 PD-specific miRNAs in
      our study. Analysis of the mTF-miRNA-gene-gTF network about PD-specific genes
      revealed two feed-forward loops: one involving the SPRK2 gene, hsa-miR-19a-3p and
      SPI1, and the second involving the SPRK2 gene, hsa-miR-17-3p and SPI. The long
      non-coding RNA (lncRNA)-mediated regulatory network identified lncRNAs associated
      with PD-specific genes and PD-specific miRNAs. Moreover, single nucleotide
      polymorphism (SNP) analysis of the PD-specific genes identified two significant
      SNPs, and SNP analysis of the neurodegenerative disease-specific genes identified
      seven significant SNPs. Most of these SNPs are present in the 3'-untranslated
      region of genes and are controlled by several miRNAs. CONCLUSION: Our study
      identified a total of 53 common DEGs in PD patients compared with healthy
      controls in blood and brain datasets and five of these genes were previously
      linked with PD. Regulatory network analysis identified PD-specific miRNAs,
      associated long non-coding RNA and feed-forward loops, which contribute to our
      understanding of the mechanisms underlying PD. The SNPs identified in our study
      can determine whether a genetic variant is associated with PD. Overall, these
      findings will help guide our study of the complex molecular mechanism of PD.

PMID- 29653597
TI  - Phosphorylated TDP-43 (pTDP-43) aggregates in the axial skeletal muscle of
      patients with sporadic and familial amyotrophic lateral sclerosis.
AB  - Muscle atrophy with weakness is a core feature of amyotrophic lateral sclerosis
      (ALS) that has long been attributed to motor neuron loss alone. However, several
      studies in ALS patients, and more so in animal models, have challenged this
      assumption with the latter providing direct evidence that muscle can play an
      active role in the disease. Here, we examined the possible role of cell
      autonomous pathology in 148 skeletal muscle samples from 57 ALS patients,
      identifying phosphorylated TAR DNA-binding protein (pTDP-43) inclusions in the
      muscle fibers of 19 patients (33.3%) and 24 tissue samples (16.2% of specimens).
      A muscle group-specific difference was identified with pTDP-43 pathology being
      significantly more common in axial (paraspinous, diaphragm) than appendicular
      muscles (P = 0.0087). This pathology was not significantly associated with
      pertinent clinical, genetic (c9ALS) or nervous system pathologic data, suggesting
      it is not limited to any particular subgroup of ALS patients. Among 25 non-ALS
      muscle samples, pTDP-43 inclusions were seen only in the autophagy-related
      disorder inclusion body myositis (IBM) (n = 4), where they were more diffuse than
      in positive ALS samples (P = 0.007). As in IBM samples, pTDP-43 aggregates in ALS
      were p62/ sequestosome-1-positive, potentially indicating induction of autophagy.
      Phospho-TDP-43-positive ALS and IBM samples also showed significant up-regulation
      of TARDBP and SQSTM1 expression. These findings implicate axial skeletal muscle
      as an additional site of pTDP-43 pathology in some ALS patients, including
      sporadic and familial cases, which is deserving of further investigation.

PMID- 29653598
TI  - Economic impact of bovine cysticercosis and taeniosis caused by Taenia saginata
      in Belgium.
AB  - BACKGROUND: Bovine cysticercosis (BCC) (due to Taenia saginata) is often claimed
      to cause considerable economic losses to the livestock industry, particularly in
      beef cattle, but recent studies estimating the economic impact are lacking. The
      current study aimed to quantify the annual economic impact of BCC in Belgium from
      2012 to 2016, by gathering data from diverse sources in the meat and human health
      sectors. RESULTS: In Belgium, on average, 15 carcasses with generalised
      infections and 1168 carcasses with localised ones are detected upon meat
      inspection each year. The highest proportion of the total economic losses due to
      bovine cysticercosis were borne by the cattle owners with an average economic
      cost of ?3,408,455/year: ?2,954,061/year due to BCC insurance, ?453,024/year due
      to value losses of beef of uninsured carcasses (i.e. freezing process) and
      ?1370/year due to destruction costs of uninsured carcasses with generalised
      infections. The slaughterhouses suffered an economic impact of ?210,806/year.
      They were responsible for inspection costs related to meat inspection in general,
      administration, processing and deboning of infected carcasses (?597,856/year),
      value losses (?34,848/year) and destruction costs (?105/year) of carcasses
      insured by the slaughterhouses (unofficial insurance) (5% of slaughtered
      animals). On the other hand, the slaughterhouses gained a total of ?422,004/year
      due to unofficial insurance fees. Thirty percent of all slaughtered animals were
      officially insured against BCC and the insurance company generated an income of
      ?2,322,337/year. The economic impact related to taeniosis (10,991 patients
      annually) amounted to a maximum of ?795,858/year. CONCLUSION: BCC and taeniosis
      due to T. saginata have a large economic impact in Belgium, mainly due to the
      insurance costs for BCC. These results indicate the need for reducing the number
      of BCC and taeniosis cases to avoid the costs and losses related to this
      parasite.

PMID- 29653599
TI  - Effects of antibiotic treatment on the fecundity of Rhipicephalus
      haemaphysaloides ticks.
AB  - BACKGROUND: Endosymbiotic bacteria inhabit a variety of arthropods including
      ticks and may have multiple effects on the host's survival, reproduction or
      pathogen acquisition and transmission. Rhipicephalus haemaphysaloides is one of
      the most widely distributed tick species in China. The symbiotic bacteria
      composition and their impacts to R. haemaphysaloides ticks have not been studied.
      The present study investigated the composition of microbial community in R.
      haemaphysaloides ticks and then assessed the effects of endosymbionts on the
      host's fecundity by antibiotic treatment experiments. METHODS: The microbial
      population of female and male R. haemaphysaloides ticks was analyzed using
      Illumina Miseq sequencing of 16S rRNA gene. Thirty engorged female ticks were
      then randomly divided into five groups and injected with ampicillin,
      ciprofloxacin, kanamycin, tetracycline, or phosphate-buffered solution (PBS),
      respectively. Effects of antibiotic treatments on maternal oviposition, egg
      hatching and density of endosymbionts were evaluated. RESULTS: Illumina Miseq
      sequencing showed that Coxiella and Rickettsia were the predominant bacterial
      genera inhabiting R. haemaphysaloides ticks. Antibiotic treatment experiments
      found that kanamycin reduced the density of Coxiella-like endosymbiont (Coxiella
      LE hereafter) in eggs, ciprofloxacin reduced the density of Rickettsia-like
      endosymbiont (Rickettsia-LE), and tetracycline had effect on both endosymbionts,
      while ampicillin affected neither. Meanwhile hatching rates of eggs were observed
      to decrease greatly in the kanamycin or tetracycline-treated group but maintained
      in the ampicillin or ciprofloxacin-treated group. Furthermore, the reduced
      hatching rates were found to be associated with density of Coxiella-LE in eggs.
      CONCLUSIONS: The findings indicate that Coxiella-LE is essential for the
      reproduction of R. haemaphysaloides ticks, and that kanamycin can be used to
      study the role of Coxiella-LE on ticks.

PMID- 29653601
TI  - Erratum to "Neurotrophins and specific receptors in the oviduct tracts of
      Japanese quail (Coturnix coturnix japonica)" [AANAT 210C (2017) 112-120].

PMID- 29653600
TI  - First record of the nematode Libyostrongylus dentatus Hoberg, Lloyd & Omar, 1995
      (Trichostrongylidae) in ostriches (Struthio camelus Linnaeus, 1758)
      (Struthionidae) outside the Americas.
AB  - BACKGROUND: Libyostrongylus douglassii, Libyostrongylus dentatus and
      Libyostrongylus magnus are nematodes that infect ostriches. The first species has
      been identified in ostriches from Africa, Europe, Americas and Oceania. Although
      the natural range of ostriches is Africa, L. dentatus was first described in
      birds from the USA and later identified in Brazil, where co-infections with L.
      douglassii have been commonly reported. Libyostrongylus magnus is known from the
      original description only. There are a few reports on infections with L.
      douglassii in ostriches from Africa and all farmed birds examined are from the
      southern region of the continent. The aim of this report was to verify
      Libyostrongylus spp. infections in wild ostriches from Ethiopia. Fecal samples
      from ostriches, Struthio molybdophanes, were collected and submitted to
      coproculture. Infective larvae were identified to the species level based on
      general morphology and morphometry. In addition, phylogenetic analysis of the
      first and second internal transcribed spacer (ITS1 and ITS2) of the nuclear
      ribosomal DNA was performed. RESULTS: Infective larvae from Ethiopian ostriches
      had the morphological characteristics of L. dentatus. Confidence interval
      estimate for sheath tail length from Ethiopian Libyostrongylus sp. isolates
      overlapped one for Brazilian L. dentatus. Neighbor-joining and Maximum Likelihood
      phylogenetic trees based on sequences of the ITS1 and ITS2 regions revealed that
      the Ethiopian samples belong to the L. dentatus species clade. Monospecific
      infections with L. dentatus were confirmed in Ethiopian wild ostriches, opposed
      to the co-infections typically found in the Americas. CONCLUSIONS: To our
      knowledge, this is the first record of L. dentatus from African ostriches, the
      region from which this parasite originated.

PMID- 29653602
TI  - Reply to: A protocolized approach to veno-arterial extracorporeal membrane
      oxygenation for massive pulmonary embolism.

PMID- 29653603
TI  - Guidelines for post-resuscitation care should include management of acute kidney
      injury and use of renal replacement therapy.

PMID- 29653604
TI  - Reply to: Guidelines for post-resuscitation care should include management of
      acute kidney injury and use of renal replacement therapy.

PMID- 29653605
TI  - Future prospects and challenges for Alzheimer's disease drug development in the
      era of the NIA-AA Research Framework.

PMID- 29653608
TI  - NIA commentary on the NIA-AA Research Framework: Towards a biological definition
      of Alzheimer's disease.

PMID- 29653607
TI  - The National Institute on Aging and the Alzheimer's Association Research
      Framework for Alzheimer's disease: Perspectives from the Research Roundtable.
AB  - The Alzheimer's Association's Research Roundtable met in November 2017 to explore
      the new National Institute on Aging and the Alzheimer's Association Research
      Framework for Alzheimer's disease. The meeting allowed experts in the field from
      academia, industry, and government to provide perspectives on the new National
      Institute on Aging and the Alzheimer's Association Research Framework. This
      review will summarize the "A, T, N System" (Amyloid, Tau, and Neurodegeneration)
      using biomarkers and how this may be applied to clinical research and drug
      development. In addition, challenges and barriers to the potential adoption of
      this new framework will be discussed. Finally, future directions for research
      will be proposed.

PMID- 29653610
TI  - Abnormal white matter: Expanding the GLUT1-D phenotype.

PMID- 29653609
TI  - Further expansion of the genetic GABA-A-opathies.

PMID- 29653611
TI  - #VaccinesWork... don't they?

PMID- 29653612
TI  - The fog of development: evaluating the Millennium Villages Project.

PMID- 29653606
TI  - NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease.
AB  - In 2011, the National Institute on Aging and Alzheimer's Association created
      separate diagnostic recommendations for the preclinical, mild cognitive
      impairment, and dementia stages of Alzheimer's disease. Scientific progress in
      the interim led to an initiative by the National Institute on Aging and
      Alzheimer's Association to update and unify the 2011 guidelines. This unifying
      update is labeled a "research framework" because its intended use is for
      observational and interventional research, not routine clinical care. In the
      National Institute on Aging and Alzheimer's Association Research Framework,
      Alzheimer's disease (AD) is defined by its underlying pathologic processes that
      can be documented by postmortem examination or in vivo by biomarkers. The
      diagnosis is not based on the clinical consequences of the disease (i.e.,
      symptoms/signs) in this research framework, which shifts the definition of AD in
      living people from a syndromal to a biological construct. The research framework
      focuses on the diagnosis of AD with biomarkers in living persons. Biomarkers are
      grouped into those of beta amyloid deposition, pathologic tau, and
      neurodegeneration [AT(N)]. This ATN classification system groups different
      biomarkers (imaging and biofluids) by the pathologic process each measures. The
      AT(N) system is flexible in that new biomarkers can be added to the three
      existing AT(N) groups, and new biomarker groups beyond AT(N) can be added when
      they become available. We focus on AD as a continuum, and cognitive staging may
      be accomplished using continuous measures. However, we also outline two different
      categorical cognitive schemes for staging the severity of cognitive impairment: a
      scheme using three traditional syndromal categories and a six-stage numeric
      scheme. It is important to stress that this framework seeks to create a common
      language with which investigators can generate and test hypotheses about the
      interactions among different pathologic processes (denoted by biomarkers) and
      cognitive symptoms. We appreciate the concern that this biomarker-based research
      framework has the potential to be misused. Therefore, we emphasize, first, it is
      premature and inappropriate to use this research framework in general medical
      practice. Second, this research framework should not be used to restrict
      alternative approaches to hypothesis testing that do not use biomarkers. There
      will be situations where biomarkers are not available or requiring them would be
      counterproductive to the specific research goals (discussed in more detail later
      in the document). Thus, biomarker-based research should not be considered a
      template for all research into age-related cognitive impairment and dementia;
      rather, it should be applied when it is fit for the purpose of the specific
      research goals of a study. Importantly, this framework should be examined in
      diverse populations. Although it is possible that beta-amyloid plaques and
      neurofibrillary tau deposits are not causal in AD pathogenesis, it is these
      abnormal protein deposits that define AD as a unique neurodegenerative disease
      among different disorders that can lead to dementia. We envision that defining AD
      as a biological construct will enable a more accurate characterization and
      understanding of the sequence of events that lead to cognitive impairment that is
      associated with AD, as well as the multifactorial etiology of dementia. This
      approach also will enable a more precise approach to interventional trials where
      specific pathways can be targeted in the disease process and in the appropriate
      people.

PMID- 29653613
TI  - Lessons from the Millennium Villages Project: a personal perspective.

PMID- 29653614
TI  - Inequalities in child mortality: real data or modelled estimates?

PMID- 29653615
TI  - Reducing the risk of postoperative trichiasis: lessons from a clinical trial.

PMID- 29653616
TI  - Humanitarian disaster for Rohingya refugees: impending natural hazards and
      worsening public health crises.

PMID- 29653617
TI  - A new era for community health in countries of low and middle income?

PMID- 29653618
TI  - Community health and equity of outcomes: the Partners In Health experience.

PMID- 29653619
TI  - Can Zika virus antibodies cross-protect against dengue virus?

PMID- 29653620
TI  - Can Zika virus antibodies cross-protect against dengue virus? - Authors' reply.

PMID- 29653621
TI  - Observations from indigenous languages in Northern Territory, Australia.

PMID- 29653623
TI  - Correction to Lancet Glob Health 2018; 6: e447-59.

PMID- 29653622
TI  - Authorship trends in The Lancet Global Health: only the tip of the iceberg?

PMID- 29653624
TI  - Correction to Lancet Glob Health 2017; 5: e501-11.

PMID- 29653625
TI  - The Millennium Villages Project: a retrospective, observational, endline
      evaluation.
AB  - BACKGROUND: The Millennium Villages Project (MVP) was a 10 year, multisector,
      rural development project, initiated in 2005, operating across ten sites in ten
      sub-Saharan African countries to achieve the Millennium Development Goals (MDGs).
      In this study, we aimed to estimate the project's impact, target attainment, and
      on-site spending. METHODS: In this endline evaluation of the MVP, we
      retrospectively selected comparison villages that best matched the project
      villages on possible confounding variables. Cross-sectional survey data on 40
      outcomes of interest were collected from both the project and the comparison
      villages in 2015. Using these data, as well as on-site spending data collected
      during the project, we estimated project impacts as differences in outcomes
      between the project and comparison villages; target attainment as differences
      between project outcomes and prespecified targets; and on-site spending as
      expenditures reported by communities, donors, governments, and the project.
      Spending data were not collected in the comparison villages. FINDINGS: Averaged
      across the ten project sites, we found that impact estimates for 30 of 40
      outcomes were significant (95% uncertainty intervals [UIs] for these outcomes
      excluded zero) and favoured the project villages. In particular, substantial
      effects were seen in agriculture and health, in which some outcomes were roughly
      one SD better in the project villages than in the comparison villages. The
      project was estimated to have no significant impact on the consumption-based
      measures of poverty, but a significant favourable impact on an index of asset
      ownership. Impacts on nutrition and education outcomes were often inconclusive
      (95% UIs included zero). Averaging across outcomes within categories, the project
      had significant favourable impacts on agriculture, nutrition, education, child
      health, maternal health, HIV and malaria, and water and sanitation. A third of
      the targets were met in the project sites. Total on-site spending decreased from
      US$132 per person in the first half of the project (of which $66 was from the
      MVP) to $109 per person in the second half of the project (of which $25 was from
      the MVP). INTERPRETATION: The MVP had favourable impacts on outcomes in all MDG
      areas, consistent with an integrated rural development approach. The greatest
      effects were in agriculture and health, suggesting support for the project's
      emphasis on agriculture and health systems strengthening. The project
      conclusively met one third of its targets. FUNDING: The Open Society Foundations,
      the Islamic Development Bank, and the governments of Japan, South Korea, Mali,
      Senegal, and Uganda.

PMID- 29653626
TI  - Effective interventions for unintentional injuries: a systematic review and
      mortality impact assessment among the poorest billion.
AB  - BACKGROUND: Between 1990 and 2015, the global injury mortality declined, but in
      countries where the poorest billion live, injuries are becoming an increasingly
      prevalent cause of death. The vulnerability of this population requires immediate
      attention from policy makers to implement effective interventions that lessen the
      burden of injuries in these countries. Our aim was two-fold; first, to review all
      the evidence on effective interventions for the five main types of unintentional
      injury; and second, to estimate the potential number of lives saved by effective
      injury interventions among the poorest billion. METHODS: For our systematic
      review we used references in the Disability Control Priorities third edition, and
      searched PubMed and the Cochrane database for papers published until Sept 10,
      2016, using a comprehensive search strategy to find interventions for the five
      major causes of unintentional injuries: road traffic crashes, falls, drowning,
      burns, and poisoning. Studies were included if they presented evidence with
      significant effects sizes for any outcome; no inclusions or exclusions made on
      the basis of where the study was carried out (ie, low-income, middle-income, or
      high-income country). Then we used data from the Global Burden of Disease 2015
      study and a Monte Carlo simulation technique to estimate the potential annual
      attributable number of lives saved among the poorest billion by these evidence
      based injury interventions. We estimated results for 84 countries where the
      poorest billion live. FINDINGS: From the 513 papers identified, 47 were eligible
      for inclusion. We identified 11 interventions that had an effect on injury
      mortality. For road traffic deaths, the most successful interventions in
      preventing deaths are speed enforcement (>80 000 lives saved per year) and drink
      driving enforcement (>60 000 lives saved per year). Interventions potentially
      most effective in preventing deaths from drowning are formal swimming lessons for
      children younger than 14 years (>25 000 lives saved per year) and the use of
      creches to supervise younger children (younger than 5 years; >10 000 lives saved
      per year). We did not find sufficient evidence on interventions for other causes
      of unintentional injuries (poisoning, burns, and falls) to run similar
      simulations. INTERPRETATION: Based on the little available evidence, key
      interventions have been identified to prevent lives lost from unintentional
      injuries among the poorest billion. This Article provides guidance to national
      authorities on evidence-based priority interventions that can reduce the burden
      of injuries among the most vulnerable members of the population. We also identify
      an important gap in knowledge on the effectiveness and the mortality impacts of
      injury interventions. FUNDING: Partly supported by the Fogarty International
      Center of the US National Institutes of Health (Chronic Consequences of Trauma,
      Injuries, Disability Across the Lifespan: Uganda; #D43TW009284).

PMID- 29653627
TI  - National and regional under-5 mortality rate by economic status for low-income
      and middle-income countries: a systematic assessment.
AB  - BACKGROUND: The progress to achieve the fourth Millennium Development Goal in
      reducing mortality rate in children younger than 5 years since 1990 has been
      remarkable. However, work remains to be done in the Sustainable Development Goal
      era. Estimates of under-5 mortality rates at the national level can hide
      disparities within countries. We assessed disparities in under-5 mortality rates
      by household economic status in low-income and middle-income countries (LMICs).
      METHOD: We estimated country-year-specific under-5 mortality rates by wealth
      quintile on the basis of household wealth indices for 137 LMICs from 1990 to
      2016, using a Bayesian statistical model. We estimated the association between
      quintile-specific and national-level under-5 mortality rates. We assessed the
      levels and trends of absolute and relative disparity in under-5 mortality rate
      between the poorest and richest quintiles, and among all quintiles. FINDINGS: In
      2016, for all LMICs (excluding China), the aggregated under-5 mortality rate was
      64.6 (90% uncertainty interval [UI] 61.1-70.1) deaths per 1000 livebirths in the
      poorest households (first quintile), 31.3 (29.5-34.2) deaths per 1000 livebirths
      in the richest households (fifth quintile), and in between those outcomes for the
      middle quintiles. Between 1990 and 2016, the largest absolute decline in under-5
      mortality rate occurred in the two poorest quintiles: 77.6 (90% UI 71.2-82.6)
      deaths per 1000 livebirths in the poorest quintile and 77.9 (72.0-82.2) deaths
      per 1000 livebirths in the second poorest quintile. The difference in under-5
      mortality rate between the poorest and richest quintiles decreased significantly
      by 38.8 (90% UI 32.9-43.8) deaths per 1000 livebirths between 1990 and 2016. The
      poorest to richest under-5 mortality rate ratio, however, remained similar (2.03
      [90% UI 1.94-2.11] in 1990, 1.99 [1.91-2.08] in 2000, and 2.06 [1.92-2.20] in
      2016). During 1990-2016, around half of the total under-5 deaths occurred in the
      poorest two quintiles (48.5% in 1990 and 2000, 49.5% in 2016) and less than a
      third were in the richest two quintiles (30.4% in 1990, 30.5% in 2000, 29.9% in
      2016). For all regions, differences in the under-5 mortality rate between the
      first and fifth quintiles decreased significantly, ranging from 20.6 (90% UI 15.9
      25.1) deaths per 1000 livebirths in eastern Europe and central Asia to 59.5 (48.5
      70.4) deaths per 1000 livebirths in south Asia. In 2016, the ratios of under-5
      mortality rate in the first quintile to under-5 mortality rate in the fifth
      quintile were significantly above 2.00 in two regions, with 2.49 (90% UI 2.15
      2.87) in east Asia and Pacific (excluding China) and 2.41 (2.05-2.80) in south
      Asia. Eastern and southern Africa had the smallest ratio in 2016 at 1.62 (90% UI
      1.48-1.76). Our model suggested that the expected ratio of under-5 mortality rate
      in the first quintile to under-5 mortality rate in the fifth quintile increases
      as national-level under-5 mortality rate decreases. INTERPRETATION: For all LMICs
      (excluding China) combined, the absolute disparities in under-5 mortality rate
      between the poorest and richest households have narrowed significantly since
      1990, whereas the relative differences have remained stable. To further narrow
      the rich-and-poor gap in under-5 mortality rate on the relative scale, targeted
      interventions that focus on the poorest populations are needed. FUNDING: National
      University of Singapore, UN Children's Fund, United States Agency for
      International Development, and the Bill & Melinda Gates Foundation.

PMID- 29653628
TI  - Changing cancer survival in China during 2003-15: a pooled analysis of 17
      population-based cancer registries.
AB  - BACKGROUND: From 2003 to 2005, standardised 5-year cancer survival in China was
      much lower than in developed countries and varied substantially by geographical
      area. Monitoring population-level cancer survival is crucial to the understanding
      of the overall effectiveness of cancer care. We therefore aimed to investigate
      survival statistics for people with cancer in China between 2003 and 2015.
      METHODS: We used population-based data from 17 cancer registries in China. Data
      for the study population was submitted by the end of July 31, 2016, with follow
      up data on vital status obtained on Dec 31, 2015. We used anonymised, individual
      cancer registration records of patients (aged 0-99 years) diagnosed with primary,
      invasive cancers from 2003 to 2013. Patients eligible for inclusion had data for
      demographic characteristics, date of diagnosis, anatomical site, morphology,
      behaviour code, vital status, and last date of contact. We analysed 5-year
      relative survival by sex, age, and geographical area, for all cancers combined
      and 26 different cancer types, between 2003 and 2015. We stratified survival
      estimates by calendar period (2003-05, 2006-08, 2009-11, and 2012-15). FINDINGS:
      There were 678 842 records of patients with invasive cancer who were diagnosed
      between 2003 and 2013. Of these records, 659 732 (97.2%) were eligible for
      inclusion in the final analyses. From 2003-05 to 2012-15, age-standardised 5-year
      relative survival increased substantially for all cancers combined, for both male
      and female patients, from 30.9% (95% CI 30.6-31.2) to 40.5% (40.3-40.7). Age
      standardised 5-year relative survival also increased for most cancer types,
      including cancers of the uterus (average change per calendar period 5.5% [95% CI
      2.5-8.5]), thyroid (5.4% [3.2-7.6]), cervix (4.5% [2.9-6.2]), and bone (3.2% [2.1
      4.4]). In 2012-15, age-standardised 5-year survival for all patients with cancer
      was higher in urban areas (46.7%, 95% CI 46.5-47.0) than in rural areas (33.6%,
      33.3-33.9), except for patients with oesophageal or cervical cancer; but
      improvements in survival were greater for patients residing in rural areas than
      in urban areas. Relative survival decreased with increasing age. The increasing
      trends in survival were consistent with the upward trends of medical expenditure
      of the country during the period studied. INTERPRETATION: There was a marked
      overall increase in cancer survival from 2003 to 2015 in the population covered
      by these cancer registries in China, possibly reflecting advances in the quality
      of cancer care in these areas. The survival gap between urban and rural areas
      narrowed over time, although geographical differences in cancer survival
      remained. Insight into these trends will help prioritise areas that need
      increased cancer care. FUNDING: National Key R&D Program of China, PUMC Youth
      Fund and the Fundamental Research Funds for the Central Universities, and Major
      State Basic Innovation Program of the Chinese Academy of Medical Sciences.

PMID- 29653630
TI  - A "shocking" new code status.

PMID- 29653629
TI  - Oral doxycycline for the prevention of postoperative trachomatous trichiasis in
      Ethiopia: a randomised, double-blind, placebo-controlled trial.
AB  - BACKGROUND: Trachomatous trichiasis is treated surgically to prevent sight loss.
      Unfavourable surgical outcomes remain a major challenge. We investigated the
      hypothesis that doxycycline might reduce the risk of postoperative trichiasis
      following surgery in patients with trachomatous trichiasis through anti-matrix
      metalloproteinase and anti-inflammatory activity. METHODS: In this randomised,
      double-blind, placebo-controlled trial, adults (aged >18 years) with upper lid
      trachomatous trichiasis in association with tarsal conjunctive scarring were
      recruited through community-based screening and surgical outreach campaigns in
      Ethiopia. Individuals who had previously had eyelid surgery were excluded.
      Participants were randomly assigned (1:1), with random block sizes of four or
      six, to receive oral doxycycline (100 mg once a day) or placebo for 28 days
      immediately after trichiasis surgery. Randomisation was stratified by surgeon.
      Patients, investigators, surgeons, and all other study team members were masked
      to study group allocation and treatment. Participants were examined at 10 days,
      and 1, 6, and 12 months after surgery. The primary outcome was the cumulative
      proportion of individuals who developed postoperative trichiasis by 12 months.
      Primary analyses were done in all participants who attended at least one of the
      four follow-up assessments. Safety analyses were done in all participants who
      attended either the 10 day or 1 month follow-up assessments. This trial is
      registered with the Pan African Clinical Trials Registry, number
      PACTR201512001370307. FINDINGS: Between Dec 21, 2015, and April 6, 2016, 1000
      patients with trichiasis were enrolled and randomly assigned to treatment (499
      patients to doxycycline, 501 patients to placebo). All but one participant
      attended at least one follow-up assessment. Thus, 999 participants were assessed
      for the primary outcome: 498 in the doxycycline group and 501 in the placebo
      group. By month 12, 58 (12%) of 498 patients in the doxycycline group and 62
      (12%) of 501 patients in the placebo group had developed postoperative trichiasis
      (adjusted odds ratio 0.91, 95% CI 0.61 to 1.34, p=0.63), with a risk difference
      of -0.5% (-4.5% to 3.5%). Significantly more patients in the doxycycline group
      had an adverse event than in the placebo group (18 [4%] of 498 vs six [1%] of
      501; odds ratio 3.09, 95% CI 1.21-7.84; p=0.02). The most frequent adverse events
      in the doxycycline group were gastritis symptoms (n=9), constipation (n=4), and
      diarrhoea (n=4). INTERPRETATION: Doxycycline did not reduce the risk of
      postoperative trichiasis and is therefore not indicated for the improvement of
      outcomes following trachomatous trichiasis surgery. Surgical programmes should
      continue to make efforts to strengthen surgical training and supervision to
      improve outcomes. FUNDING: The Wellcome Trust.

PMID- 29653632
TI  - Outcomes of hospitalization in adults with Fontan palliation: The Mayo Clinic
      experience.
AB  - : The outcomes of hospitalization in the Fontan population have not been
      specifically studied. The purpose of this study was to describe outcomes of
      hospitalization (frequency and indications for hospitalization, and in-hospital
      mortality) in this population and to determine how these outcomes differ from
      those of other adults with congenital heart disease (CHD). METHODS: This was a
      retrospective study of adult Fontan patients hospitalized at Mayo Clinic
      Rochester in 1990-2015. We selected age- and gender-matched control group of
      patients with repaired CHD and biventricular circulation hospitalized within the
      study period. RESULTS: A total of 367 Fontan patients (age 31+/-7 years and 259
      [71%] with atriopulmonary Fontan) had 853 hospital admissions in 4 years (58
      hospitalizations per 100 patient-years). The most common indications were
      arrhythmia (n=188, 22%), heart failure (n=169, 20%), and cardiac surgery (n=133,
      16%). Overall in-hospital mortality was 4% (n=38), and the highest in-hospital
      mortality occurred in patients hospitalized for cardiac surgery (n=15, 11%) and
      heart failure (n=13, 8%). In comparison to the repaired CHD and biventricular
      circulation group, the Fontan group had more frequent hospitalizations (22 vs 58
      per 100 patient-years, P<.001) and higher overall in-hospital mortality (1% vs
      5%, P<.001), mortality after cardiac surgery (2% vs 11%, P=.01), and mortality
      for heart failure-related hospitalizations (2% vs 8%, P=.04). CONCLUSIONS: Adults
      with Fontan palliation had more frequent hospitalization and in-hospital
      mortality compared to the rest of the CHD population. Arrhythmia and heart
      failure were the most common indications for hospitalization. Perhaps optimal
      management of heart failure and arrhythmia may improve outcomes in this
      population.

PMID- 29653631
TI  - Impact of hormone therapy on Medicare spending in the Women's Health Initiative
      randomized clinical trials.
AB  - BACKGROUND: Randomized trials can compare economic as well as clinical outcomes,
      but economic data are difficult to collect. Linking clinical trial data with
      Medicare claims could provide novel information on health care utilization and
      cost. METHODS: We linked data from Medicare claims of women >=65 years old who
      had Medicare fee-for-service coverage with their clinical data from the Women's
      Health Initiative trials of conjugated equine estrogens plus medroxyprogesterone
      acetate (CEE+MPA) versus placebo and of CEE-alone versus placebo. The primary
      outcome was total Medicare spending during the intervention phase of the trial,
      and the secondary outcomes were spending on diseases hypothesized a priori to be
      sensitive to the effects of hormone therapy. RESULTS: In the CEE+MPA trial, 4,557
      participants >=65 years old were included. Women randomly assigned to CEE+MPA had
      4% higher mean Medicare spending overall ($45,690 vs $43,920, P = .08) but 0.5%
      lower spending for hormone-sensitive diseases ($3,526 vs $3,547, P = .07), with
      73% higher spending for coronary heart disease (P = .045) and 122% higher
      spending for pulmonary embolism (P = .026). In the CEE-alone trial, 3,107
      participants were included. Total spending among women randomly assigned to CEE
      was 3.3% higher ($75,411 vs $72,997, P = .16), and 1.7% higher spending for
      hormone-sensitive diseases ($5,213 vs $5,127, P = .57), but with 39% lower
      spending for hip fracture (p<0.03). CONCLUSIONS: Menopausal hormone therapy
      increased spending for some diseases, but decreased spending for others. These
      offsetting effects led to modest (3%-4%), nonsignificant increases in overall
      spending among women aged 65 years and older.

PMID- 29653633
TI  - Permanent pacemaker use among patients with heart failure and preserved ejection
      fraction: Findings from the Acute Decompensated Heart Failure National Registry
      (ADHERE) National Registry.
AB  - BACKGROUND: Heart failure with preserved ejection fraction may be associated with
      chronotropic incompetence, but little is known about the incidence and prevalence
      of permanent pacemaker use in this population or factors associated with its use.
      METHODS: We analyzed patients with heart failure with preserved ejection fraction
      (ie, left ventricular ejection fraction greater than 40%) from the ADHERE
      registry (2001-2006) linked with Medicare claims. We described the use of both
      prevalent and incident permanent pacemakers in heart failure with preserved
      ejection fraction and determined factors associated with pacemaker use with
      logistic regression models. RESULTS: Among 13,881 patients with heart failure
      with preserved ejection fraction, 3136 (22.6%) had a permanent pacemaker, and of
      these patients, 636 had a permanent pacemaker implanted during hospitalization.
      Permanent pacemaker use was more common among older patients (81 vs 79 years; P <
      .001), men (38% vs 34%; P < .001), patients with atrial fibrillation (58% vs 36%;
      P < .001), and patients with wider QRS duration (140 ms vs 94 ms; P < .001).
      Rates of digoxin, aldosterone antagonist, and loop diuretic use were slightly
      higher in patients with a permanent pacemaker compared with patients with no
      permanent pacemaker. Factors associated with both prevalent and incident
      pacemaker use included age, fast or slow heart rate, atrial fibrillation, and
      lower body mass index. CONCLUSIONS: Use of permanent pacemakers is relatively
      common among patients with heart failure with preserved ejection fraction.

PMID- 29653634
TI  - Rationale and design of the Statins Evaluation in Coronary procedUres and
      REvascularization: The SECURE-PCI Trial.
AB  - BACKGROUND: Previous evidence suggests that acute treatment with statins reduce
      atherosclerotic complications, including periprocedural myocardial infarction,
      but currently, there are no large, adequately powered studies to define the
      effects of early, high-dose statins in patients with acute coronary syndrome
      (ACS) and planned invasive management. OBJECTIVES: The main goal of Statins
      Evaluation in Coronary procedUres and REvascularization (SECURE-PCI) Trial is to
      determine whether the early use of a loading dose of 80 mg of atorvastatin before
      an intended percutaneous coronary intervention followed by an additional dose of
      80 mg 24 hours after the procedure will be able to reduce the rates of major
      cardiovascular events at 30 days in patients with an ACS. DESIGN: The SECURE-PCI
      study is a pragmatic, multicenter, double-blind, placebo-controlled randomized
      trial planned to enroll around 4,200 patients in 58 different sites in Brazil.
      The primary outcome is the rate of major cardiovascular events at 30 days defined
      as a composite of all-cause mortality, nonfatal acute myocardial infarction,
      nonfatal stroke, and coronary revascularization. SUMMARY: The SECURE PCI is a
      large randomized trial testing a strategy of early, high-dose statin in patients
      with ACS and will provide important information about the acute treatment of this
      patient population.

PMID- 29653635
TI  - ASCEND: A Study of Cardiovascular Events iN Diabetes: Characteristics of a
      randomized trial of aspirin and of omega-3 fatty acid supplementation in 15,480
      people with diabetes.
AB  - OBJECTIVES: The use of aspirin for the secondary prevention of cardiovascular
      disease (CVD) is firmly established, and the proportional reductions in heart
      attacks and strokes appear to be similar in people with and without diabetes.
      Uncertainty remains about the role of antiplatelet treatments for primary
      prevention of CVD, and guidelines vary in their recommendations. It has also been
      hypothesized that long-term aspirin can prevent gastro-intestinal and other
      cancers. Observational studies suggest associations between higher intakes of
      omega-3 fatty acids (FA) and lower rates of CVD, but there is no large-scale
      randomized evidence to support using prophylactic omega-3 FA supplementation in
      primary prevention. ASCEND is a randomized trial assessing whether 100 mg daily
      aspirin safely prevents CVD and cancer in patients with diabetes without known
      arterial disease. It is also assessing whether supplementation with 1 g omega-3
      FA daily prevents CVD. This paper describes the methods and baseline
      characteristics of the randomized participants. METHODS AND RESULTS: Between 2005
      and 2011, using mail-based methods, 15,480 people with diabetes were randomized
      to aspirin versus placebo and, in a factorial design, to omega-3 FA
      supplementation versus placebo. Blood and urine samples were collected to allow
      baseline stratification by biochemical prognostic variables (e.g. HbA1c, blood
      lipids). Follow-up is for a median of at least 7 years. CONCLUSIONS:
      Demonstrating that prophylactic aspirin safely reduces the risk of CVD or cancer
      in the primary prevention setting, or that omega-3 FA supplementation prevents
      CVD, would be relevant to hundreds of millions of people worldwide who are
      currently not receiving such therapies. The results of ASCEND will be reported in
      2018.

PMID- 29653636
TI  - Rationale and design of the comParIson Of sacubitril/valsartaN versus Enalapril
      on Effect on nt-pRo-bnp in patients stabilized from an acute Heart Failure
      episode (PIONEER-HF) trial.
AB  - OBJECTIVE: The objective is to assess the safety, tolerability, and efficacy of
      sacubitril/valsartan compared with enalapril in patients with heart failure (HF)
      with a reduced ejection fraction (EF) stabilized during hospitalization for acute
      decompensated HF. BACKGROUND: Sacubitril/valsartan, a first-in-class angiotensin
      receptor-neprilysin inhibitor, improves survival among ambulatory HF patients
      with a reduced EF. However, there is very limited experience with the in-hospital
      initiation of sacubitril/valsartan in patients who have been stabilized following
      hospitalization for acute decompensated HF. METHODS: PIONEER-HF is a 12-week,
      prospective, multicenter, double-blind, randomized controlled trial enrolling a
      planned 882 patients at more than 100 participating sites in the United States.
      Medically stable patients >18 years of age with an EF <40% and an amino terminal
      pro b-type natriuretic peptide >1600 pg/mL or b-type natriuretic peptide >400
      pg/mL are eligible for participation no earlier than 24 hours and up to 10 days
      from initial presentation while still hospitalized. Patients are randomly
      assigned 1:1 to in-hospital initiation of sacubitril/valsartan titrated to 97/103
      mg by mouth twice daily versus enalapril titrated to 10 mg by mouth twice daily
      for 8 weeks. All patients receive open-label treatment with sacubitril/valsartan
      for the remaining 4 weeks of the study. The primary efficacy end point is the
      time-averaged proportional change in amino terminal-pro b-type natriuretic
      peptide from baseline through weeks 4 and 8. Secondary and exploratory end points
      include serum and urinary biomarkers as well as clinical outcomes. Safety end
      points include the incidence of angioedema, hypotension, renal insufficiency, and
      hyperkalemia. CONCLUSION: The PIONEER-HF trial will inform clinical practice by
      providing evidence on the safety, tolerability, and efficacy of in-hospital
      initiation of sacubitril/valsartan among patients who have been stabilized
      following an admission for acute decompensated HF with a reduced EF.

PMID- 29653639
TI  - Changes in renal function in patients with atrial fibrillation: Efficacy and
      safety of the non-vitamin K antagonist oral anticoagulants.

PMID- 29653638
TI  - Government continues to have an important role in promoting cardiovascular
      health.

PMID- 29653637
TI  - Genome-wide and candidate gene approaches of clopidogrel efficacy using
      pharmacodynamic and clinical end points-Rationale and design of the International
      Clopidogrel Pharmacogenomics Consortium (ICPC).
AB  - RATIONALE: The P2Y12 receptor inhibitor clopidogrel is widely used in patients
      with acute coronary syndrome, percutaneous coronary intervention, or ischemic
      stroke. Platelet inhibition by clopidogrel shows wide interpatient variability,
      and high on-treatment platelet reactivity is a risk factor for atherothrombotic
      events, particularly in high-risk populations. CYP2C19 polymorphism plays an
      important role in this variability, but heritability estimates suggest that
      additional genetic variants remain unidentified. The aim of the International
      Clopidogrel Pharmacogenomics Consortium (ICPC) is to identify genetic
      determinants of clopidogrel pharmacodynamics and clinical response. STUDY DESIGN:
      Based on the data published on www.clinicaltrials.gov, clopidogrel intervention
      studies containing genetic and platelet function data were identified for
      participation. Lead investigators were invited to share DNA samples, platelet
      function test results, patient characteristics, and cardiovascular outcomes to
      perform candidate gene and genome-wide studies. RESULTS: In total, 17 study sites
      from 13 countries participate in the ICPC, contributing individual patient data
      from 8,829 patients. Available adenosine diphosphate-stimulated platelet function
      tests included vasodilator-stimulated phosphoprotein assay, light transmittance
      aggregometry, and the VerifyNow P2Y12 assay. A proof-of-principle analysis based
      on genotype data provided by each group showed a strong and consistent
      association between CYP2C19*2 and platelet reactivity (P value=5.1 * 10-40).
      CONCLUSION: The ICPC aims to identify new loci influencing clopidogrel efficacy
      by using state-of-the-art genetic approaches in a large cohort of clopidogrel
      treated patients to better understand the genetic basis of on-treatment response
      variability.

PMID- 29653640
TI  - Efficacy and safety of dabigatran compared with warfarin in patients with atrial
      fibrillation in relation to renal function over time-A RE-LY trial analysis.

PMID- 29653641
TI  - Health promotion: A step beyond prevention in cardiology.

PMID- 29653642
TI  - Improving patient risk communication: Translating cardiovascular risk into
      standardized risk percentiles.
AB  - BACKGROUND: Current cholesterol guidelines recommend using 10-year risk of
      atherosclerotic cardiovascular disease (ASCVD) to guide informed decisions
      regarding statin therapy, yet patients may have difficulty conceptualizing
      absolute risk estimates. Peer comparisons may provide an improved tool for
      patient risk comprehension. METHODS: Using data from the 2009-2014 National
      Health and Nutrition Examination Survey (NHANES), we estimated standardized risk
      percentiles for various age-, sex-, and race-specific subgroups based on their 10
      year ASCVD risks using the Pooled Cohort Equations. RESULTS: We examined 9160
      adults in NHANES who were free of cardiovascular disease and had complete
      clinical data. Among specific age, sex, and race groups, we estimated the
      distribution of 10-year risk, calculating the 10-year risk corresponding to each
      percentile in order to generate standardized cardiovascular risk percentiles.
      Estimated 10-year ASCVD absolute risk varied markedly by age, sex, and race
      subgroups. A 10-year risk of 7.0% would put a 55 year-old black male in the 20th
      percentile relative to his peers (ie, at lower risk than 80% of his peers),
      whereas a 10-year risk of 7.0% would put a 55 year-old white female in the 95th
      percentile (i.e., only 5% of her peers would have higher risk). Standardized
      cardiovascular risk percentiles by age, race, and sex are available online at
      populationrelativerisk.dcri.org. CONCLUSION: Cardiovascular risk varies
      substantially by age, sex, and race. These data allow for 10-year absolute risks
      of ASCVD to be translated into a standardized cardiovascular risk percentile,
      providing patients with information that is easy to understanding regarding how
      their personal risk of cardiovascular disease compares with their age-, sex-, and
      race-matched peers.

PMID- 29653643
TI  - Factors of health in the protection against death and cardiovascular disease
      among adults with subclinical atherosclerosis.
AB  - BACKGROUND: Although cardiovascular disease (CVD) prevention traditionally
      emphasizes risk factor control, recent evidence also supports the promotion of
      "health factors" associated with cardiovascular wellness. However, whether such
      health factors exist among adults with advanced subclinical atherosclerosis is
      unknown. We aimed to study the association between health factors and events
      among persons with elevated coronary artery calcium (CAC). METHODS: Self-reported
      health-factors studied included nonsmoking, physical activity, Mediterranean
      style diet, sleep quality, emotional support, low stress burden, and absence of
      depression. Measured health-factors included optimal weight, blood pressure,
      lipids, and glucose. Multivariable-adjusted Cox models examined the association
      between health factors and incident CVD or mortality, independent of risk factor
      treatment. Accelerated failure time models assessed whether health factors were
      associated with relative time delays in disease onset. RESULTS: Among 1,601 Multi
      Ethnic Study of Atherosclerosis participants with CAC >100 without baseline
      clinical atherosclerotic CVD, mean age was 69 (+/-9) years, 64% were male, and
      median CAC score was 332 Agatston units. Over 12 years of follow-up, nonsmoking,
      high-density lipoprotein cholesterol levels >40 mg/dL for men and >50 mg/dL for
      women, and low stress burden were inversely associated with ASCVD (hazard ratios
      ranging from 0.58 to 0.71, all P<.05). Nonsmoking, glucose levels <100 mg/dL,
      regular physical activity, and low stress burden were inversely associated with
      mortality (hazard ratios ranging from 0.40 to 0.77, all P<.05). Each of these
      factors was also associated with delays in onset of clinical disease, as was
      absence of depression. CONCLUSIONS: Adults with elevated CAC appear to have
      healthy lifestyle options to lower risk and delay onset of CVD, over and above
      standard preventive therapies.

PMID- 29653645
TI  - Preoperative factors associated with worsening in health-related quality of life
      following coronary artery bypass grafting in the Randomized On/Off Bypass (ROOBY)
      trial.
AB  - : For advanced coronary disease, coronary artery bypass graft (CABG) surgery
      generally improves patients' symptoms and long-term survival. Unfortunately, some
      patients experience worse health-related quality of life (HRQL) after CABG. The
      objective of this study is to report the frequency and risk factors associated
      with 1-year post-CABG HRQL deterioration. METHODS: From 2002 to 2007, 2203
      "Randomized On/Off Bypass" (ROOBY) trial patients randomly received either off
      pump or on-pump CABG at 18 VA medical centers. Subjects completed both baseline
      and 1-year Seattle Angina Questionnaire (SAQ) and the Veterans Rand 36 (VR-36)
      questionnaires to assess HRQL. Using previously published criteria, the rates of
      clinically significant changes were determined for the SAQ [angina frequency
      (AF), physical limitation (PL), and quality of life (QoL)] and VR36 [mental
      component score (MCS) and physical component score (PCS)] subscales. Multivariate
      regression models were then used to identify pre-CABG patient characteristics
      associated with worsened 1-year HRQL status for each subscale. RESULTS: Over 80%
      of patients had an improvement or no change in SAQ and VR-36 subscale scores 1
      year after CABG. The HRQL scale-specific deterioration rates were 4.5% SAQ-AF,
      16.8% SAQ-PL, 4.9% SAQ-QoL, 19.4% VR36-MCS, and 13.5% VR36-PCS. Predictors of 1
      year HRQL deterioration were diabetes and smoking for the SAQ-AF; diabetes,
      chronic obstructive pulmonary disease (COPD), and peripheral vascular disease
      (PVD) for SAQ-PL; COPD and depression for the SAQ-QoL; diabetes for VR36-PCS, and
      history of stroke and depression for VR36-MCS. The baseline score was an
      independent predictor for worsening in all the subscales studied. CONCLUSIONS:
      Among VA patients, less than 20% experienced worse HRQL 1 year after CABG. For
      patients with low symptom burden at baseline, diabetes, smoking, depression, PVD,
      COPD, and a prior stroke, clinicians should be more cautious in pre-CABG
      counseling as to their anticipated HRQL improvements.

PMID- 29653644
TI  - Bioresorbable Polymer-Coated Orsiro Versus Durable Polymer-Coated Resolute Onyx
      Stents (BIONYX): Rationale and design of the randomized TWENTE IV multicenter
      trial.
AB  - AIM: The aim was to compare in a noninferiority trial the efficacy and safety of
      2 contemporary drug-eluting stents (DESs): a novel, durable polymer-coated stent
      versus an established bioabsorbable polymer-coated stent. METHODS AND RESULTS:
      The BIONYX trial (ClinicalTrials.gov-no.NCT02508714) is an investigator
      initiated, prospective, randomized, patient- and assessor-blinded, international,
      multicenter study in all-comer patients with all types of clinical syndromes and
      lesions who require percutaneous coronary interventions with DES. Patients at 7
      study sites in the Netherlands, Belgium, and Israel were randomly assigned (1:1,
      stratified for gender and diabetes mellitus) to treatment with the novel,
      zotarolimus-eluting, durable polymer-coated Resolute Onyx stent that has a
      radiopaque, thin-strut, CoreWire stent platform versus the sirolimus-eluting,
      bioresorbable polymer-coated Orsiro stent (reference device) that has a very thin
      strut, cobalt-chromium stent backbone. The primary end point is the 1-year
      incidence of the composite clinical end point target vessel failure consisting of
      cardiac death, target vessel-related myocardial infarction, or clinically
      indicated target vessel revascularization. A power calculation, assuming a target
      vessel failure rate of 6.0% (noninferiority margin 2.5%), revealed that 2,470
      study patients would give the study 80% power (alpha level 5%), allowing for up
      to 3% loss to follow-up. The first patient was enrolled on October 7, 2015; on
      December 23, 2016, the last patient entered the study. CONCLUSIONS: BIONYX is a
      large-scale, prospective, randomized, international, multicenter trial comparing
      a novel DES with durable coating versus a reference DES with biodegradable
      coating in all-comers. The study is the first randomized assessment of the
      Resolute Onyx stent, which is an often-used DES outside the United States.

PMID- 29653646
TI  - Changes in glomerular filtration rate and outcomes in patients with atrial
      fibrillation.
AB  - BACKGROUND: Patients with kidney disease are more likely to develop atrial
      fibrillation (AF) than individuals with normal renal function, and more likely to
      suffer ischemic stroke (IS)/thromboembolism (TE). We investigated the
      relationship of kidney function evolution to IS/TE, mortality and bleeding in AF
      patients. METHODS: In a cohort of 8962 AF patients, 2653 had serum creatinine
      data, with 10894 patient-years of follow-up. Patients were stratified into
      quartiles of estimated glomerular filtration rate (eGFR) evolution (in mL/min per
      1.73 m2/year). RESULTS: Rates of events (IS/TE, bleeding, mortality) increased
      with worsening eGFR by quartiles. The risk of events was particularly increased
      when patients in the 4th quartile were compared to others. Renal impairment per
      se was not an independent predictor of IS/TE but was an independent predictor of
      bleeding, whilst eGFR worsening was an independent predictor both for IS/TE
      (Hazard Ratio [HR] 1.573, 95%CI 1.160-2.134 for patients in the last quartile)
      and for bleeding events (HR 1.543, 95%CI 1.157-2.004). Worsening eGFR did not
      improve the predictive ability of the CHA2DS2VASc and HAS-BLED scores for
      identifying a higher risk of IS/TE or bleeding events, respectively. When the
      benefit of IS reduction was balanced against the increased risk of bleeding
      events, the net clinical benefit was positive in favor of OAC use (vs non-use) in
      patients with worsening eGFR. CONCLUSIONS: Rates of IS/TE, mortality and bleeding
      increased with worsening eGFR >4.81 mL/min per 1.73 m2. Worsening eGFR was an
      independent predictor of IS/TE and of bleeding, and a better predictor of IS/TE
      than renal impairment in AF.

PMID- 29653648
TI  - Temporal changes in radial access use, associates and outcomes in patients
      undergoing PCI using rotational atherectomy between 2007 and 2014: results from
      the British Cardiovascular Intervention Society national database.
AB  - AIMS: Access site choice for cases requiring rotational atherectomy (PCI-ROTA) is
      poorly defined. Using the British Cardiovascular Intervention Society PCI
      database, temporal changes and contemporary associates/outcomes of access site
      choice for PCI-ROTA were studied. METHODS AND RESULTS: Data were analysed from
      11,444 PCI-ROTA procedures performed in England and Wales between 2007 and 2014.
      Multivariate logistic regression was used to identify predictors of access site
      choice and its association with outcomes. RESULTS: For PCI-ROTA, radial access
      increased from 19.6% in 2007 to 58.6% in 2014. Adoption of radial access was
      slower in females, those with prior CABG, and in patients with chronic occlusive
      (CTO) or left main disease. In 2013/14, the strongest predictors of femoral
      artery use were age (OR 1.02, [1.005-1.036], P = .008), CTO intervention (OR
      1.95, [1.209-3.314], P = .006), and history of previous CABG (OR 1.68, [1.124
      2.515], P = .010). Radial access was associated with reductions in overall length
      of stay, and increased rates of same-day discharge. Procedural success rates were
      similar although femoral access use was associated with increased access site
      complications (2.4 vs. 0.1%, P < .001). After adjustment for baseline
      differences, arterial complications (OR 15.6, P < .001), transfusion (OR 12.5, P
      = .023) and major bleeding OR 6.0, P < .001) remained more common with FA use.
      Adjusted mortality and MACE rates were similar in both groups. CONCLUSIONS: In
      contemporary practice, radial access for PCI-ROTA results in similar procedural
      success when compared to femoral access but is associated with shorter length of
      stay, and lower rates of vascular complication, major bleeding and transfusion.

PMID- 29653649
TI  - Two-year follow-up of patients treated with dabigatran for stroke prevention in
      atrial fibrillation: Global Registry on Long-Term Antithrombotic Treatment in
      Patients with Atrial Fibrillation (GLORIA-AF) registry.
AB  - BACKGROUND AND PURPOSE: GLORIA-AF is a large, global, prospective registry
      program of newly diagnosed atrial fibrillation (AF) patients with >=1 stroke risk
      factors. We describe the effectiveness and safety of dabigatran etexilate over 2
      years from routine clinical practice in nearly 3000 patients from GLORIA-AF who
      are newly diagnosed with non-valvular AF and at risk of stroke. METHODS:
      Consecutive enrollment into phase II of GLORIA-AF was initiated following
      approval of dabigatran for stroke prevention in non-valvular AF. Within this
      Phase II, 2937 dabigatran patients completed 2-year follow-up by May 2016 and
      were eligible for analysis. Patients who took at least 1 dose of dabigatran
      (n=2932) were used to estimate incidence rates. RESULTS: Overall incidence rates
      per 100 person-years of 0.63 (95% confidence interval [CI], 0.42-0.92) for
      stroke, 1.12 (0.83-1.49) for major bleeding, 0.47 (0.29-0.72) for myocardial
      infarction, and 2.69 (2.22-3.23) for all-cause death were observed. For patients
      taking 150 mg dabigatran twice daily (BID), corresponding rates (95% CI) were
      0.56 (0.30-0.94), 1.00 (0.64-1.47), 0.48 (0.25-0.83), and 2.07 (1.55-2.72),
      respectively. For patients taking 110 mg dabigatran BID, event rates (95% CI)
      were 0.67 (0.33-1.20), 1.16 (0.70-1.80), 0.43 (0.17-0.88), and 3.16 (2.36-4.15).
      CONCLUSIONS: These global data confirm the sustained safety and effectiveness of
      dabigatran over 2 years of follow-up, consistent with the results from clinical
      trials as well as contemporary real-world studies. WHAT IS KNOWN: * Non-vitamin K
      antagonist (VKA) anticoagulants (NOACs) are the preferred therapy for prevention
      of ischemic stroke based on phase 3 trials, but there is insufficient information
      on their efficacy and safety in daily practice, based on prospectively collected
      data. WHAT IS NEW: * This study shows that in non-valvular AF patient population,
      with up to 2 years of follow-up, the use of dabigatran led to a low incidence of
      ischemic stroke, major bleeding, and myocardial infarction in routine clinical
      care, confirming the sustained safety and effectiveness of dabigatran in clinical
      practice over 2 years of follow-up.

PMID- 29653650
TI  - Comparison of adverse event and device problem rates for transcatheter aortic
      valve replacement and Mitraclip procedures as reported by the Transcatheter Valve
      Therapy Registry and the Food and Drug Administration postmarket surveillance
      data.
AB  - BACKGROUND: Although outcomes data on transcatheter aortic valve replacement
      (TAVR) and transcatheter mitral valve repair (Mitraclip) are available via the
      Transcatheter Valve Therapy (TVT) registry, dissemination of TVT data is often
      delayed. The Food and Drug Administration's Manufacturer and User Facility Device
      Experience (MAUDE) system collects postmarket outcomes data in public medical
      device reports. We used natural language processing to compare the event rates
      for TAVR and Mitraclip in the TVT registry and from MAUDE data. METHODS: We
      identified all medical device reports related to TAVR and Mitraclip from December
      2011 through December 2014. Our primary objective was to demonstrate that event
      rates in TVT and MAUDE were not significantly different. We also compared TVT
      event rates for TAVRs performed in 2014 to MAUDE-derived event rates for the
      Sapien XT and CoreValve devices, both Food and Drug Administration-approved in
      2014. RESULTS: Regression analysis demonstrated close correlation between TVT and
      MAUDE rates for both TAVR and Mitraclip, with R2 values of 0.86 and 0.77,
      respectively. The rates for all events except bleeding were not statistically
      significantly different. We demonstrated similar increased rates of permanent
      pacemaker implantation in the 2014 TVT and MAUDE data sets consistent with
      approval of the CoreValve. CONCLUSIONS: We demonstrated that natural language
      processing technology sorted through raw MAUDE data, allowing identification of
      the most common events associated with TAVR and Mitraclip procedures, and that
      MAUDE-derived event rates were not statistically significantly different from TVT
      event rates. This technology has important public health implications because it
      improves postmarket surveillance of implantable devices and permits rapid and
      early dissemination of vital information.

PMID- 29653651
TI  - Ultrahigh-resolution ultrasound characterization of access site trauma and
      intimal hyperplasia following use of a 7F sheathless guide versus 6F sheath/guide
      combination for transradial artery PCI: Results of the PRAGMATIC trial.
AB  - : There exist limited data on the relative degree of acute injury and late
      healing of the radial artery after transradial artery (TRA) percutaneous coronary
      intervention (PCI) with a 7F sheathless guide catheter compared with a 6F
      sheath/guide combination. We used ultrahigh-resolution (55 MHz) vascular
      ultrasound to compare intimal-medial thickening (IMT) and early and late radial
      artery (RA) injury resulting from a sheathless 7F guide catheter versus a 6F
      sheath/guide combination for TRA-PCI. METHODS: Forty-one consecutive consenting
      patients undergoing elective nonemergent TRA-PCI at a single institution from
      June 2016 to December 2016 were included. Patients were randomized (stratified by
      sex) to undergo TRA-PCI using a 7F sheathless guide catheter versus a 6F
      sheath/6F guide combination. Ultrahigh-resolution vascular ultrasound (55MHz) of
      the RA access site was performed at 24hours and 90days post-TRA-PCI. The primary
      outcome of the study was a noninferiority comparison of radial artery IMT
      thickness at 90days. PCI success rates, fluoroscopy times, number of guides used,
      and crossover rates to a femoral approach were also compared. RESULTS: Baseline
      characteristics were similar between groups. Radial arterial IMT (mm) was similar
      between the 7F sheathless and 6F sheath/guide groups at 24hours (0.27 vs 0.29,
      respectively; P=.43) and at 90days (0.35 vs 0.34, respectively; P=.96). The P
      value for the noninferiority testing of a 0.07-mm limit was .002. Limited access
      site intimal tears were relatively common in both groups at 24hours (4 vs 5,
      P=.53) but often healed by 90days. Radial artery occlusion was infrequent at
      90days (2 vs 1, P=.10), and no frank dissections were noted. PCI success rates
      (100% vs 95%, P=.59), fluoroscopy times (16 vs 12minutes, P=.17), number of
      guides used (1.1 vs 1.2, P=.48), and femoral crossover rates (0% vs 0%) were
      similar between the 2 respective groups. CONCLUSIONS: A 7F sheathless approach to
      TRA-PCI results in no more IMT and early or late RA trauma than a standard 6F
      sheath/guide combination, rendering the 7F sheathless technique an attractive
      option for complex TRA-PCI.

PMID- 29653647
TI  - Prognostic value of viral eradication for major adverse cardiovascular events in
      hepatitis C cirrhotic patients.
AB  - BACKGROUND: The objective was to examine the role of a sustained virological
      response (SVR) on major adverse cardiovascular events (MACEs) in patients with
      compensated hepatitis C virus (HCV) cirrhosis. METHODS: Patients with the
      following criteria were enrolled in 35 French centers: (1) biopsy-proven HCV
      cirrhosis; (2) Child-Pugh A; (3) positive viremia; and (4) no prior liver
      complication, and then prospectively followed. All patients received HCV
      treatment after inclusion. MACEs included stroke, myocardial infarction, ischemic
      heart disease, heart failure, peripheral arterial disease, cardiac arrest, and
      cardiovascular death. SVR, defined as negative viremia 12 weeks posttreatment,
      was considered as a time-dependent covariate, and its effect on MACE occurrence
      was assessed. The median follow up was 57.5 months, ending in December 2015.
      RESULTS: Sixty-two of 878 (7.1%) patients presented a total of 79 MACEs. The main
      predictive baseline factors of MACEs were Asian ethnic origin, history of MACEs,
      arterial hypertension, diabetes mellitus, current smoking, low serum albumin
      level, high total bilirubin level, and low platelet count. In multivariate
      analysis, SVR was associated with a decreased risk of MACEs (hazard ratio=0.35,
      95% CI 0.09-0.97, P=.044), whereas Asian ethnic origin, arterial hypertension,
      smoking, and low serum albumin level remained predictive of MACE occurrence. The
      5-year survival rate was 60.1% versus 87.5% in patients who did versus those who
      did not present a MACE (P<.001). CONCLUSIONS: In patients with compensated HCV
      related cirrhosis, Asian ethnic origin, arterial hypertension, smoking, and low
      serum albumin are independent predictive factors of cardiovascular events,
      whereas an SVR is associated with a decreased rate of cardiovascular events.

PMID- 29653652
TI  - Symptomatic event reduction with extended-duration betrixaban in acute medically
      ill hospitalized patients.
AB  - BACKGROUND: Approximately 15%-30% of patients in trials of medical
      thromboprophylaxis will have missing compression ultrasound (CUS) data. The goal
      of the present analysis was to perform analyses to minimize missing data.
      METHODS: The APEX trial randomized 7,513 acutely medically ill hospitalized
      patients to thromboprophylaxis with either betrixaban for 35-42 days or
      enoxaparin for 6-14 days. A modified intent-to-treat (mITT) analysis was
      performed and included all subjects administered study drug, irrespective of CUS
      performance, and an analysis of symptomatic events which do not require
      performance of a CUS (symptomatic deep vein thrombosis, nonfatal pulmonary
      embolism, and venous thromboembolism (VTE)-related mortality). RESULTS: In the
      mITT population, betrixaban significantly reduced the primary end point (which
      included both symptomatic and CUS events) (165 [4.4%] vs 223 [6.0%]; relative
      risk = 0.75; 95% CI 0.61-0.91; P = .003; absolute risk reduction [ARR] = 1.6%;
      number needed to treat [NNT] = 63). Betrixaban also reduced symptomatic VTE
      through day 42 (35 [1.28%] vs 54 [1.88%], hazard ratio [HR] = 0.65; 95% CI 0.42
      0.99; P = .044; ARR = 0.6%; NNT=167) as well as through day 77 (37 [1.02%] vs 67
      [1.89%]; HR= 0.55; 95% CI 0.37-0.83; P = .003; ARR = 0.87%; NNT=115) as well as
      the individual end point of nonfatal pulmonary embolism (9 [0.25%] vs 20 [0.55%];
      HR= 0.45; 95% CI 0.21-0.99; P = .041; ARR = 0.30%; NNT=334). On an "as-treated"
      basis, 80 mg of betrixaban reduced VTE-related mortality through day 77 (10
      [0.34%] vs. 22 [0.79%]; HR=0.46; 95% CI 0.22-0.96; P = .035; ARR = 0.45%;
      NNT=223). CONCLUSION: In an mITT analysis of all patients administered study
      drug, extended-duration betrixaban reduced the primary end point as well as
      symptomatic events. In an as-treated analysis, 80 mg of betrixaban reduced VTE
      related death.

PMID- 29653653
TI  - Left ventricular ejection fraction reassessment post-myocardial infarction:
      Current clinical practice and determinants of adverse remodeling.
AB  - BACKGROUND: Left ventricular (LV) dysfunction may be sustained or aggravated
      during the convalescent months following an acute myocardial infarction (MI) and
      is difficult to predict. We sought to determine current practice patterns of LV
      ejection fraction (LVEF) reassessment during the months following MI and evaluate
      the predictors and clinical significance of LVEF change in a prospective post-MI
      patient cohort. METHODS: Patients with an acute MI between June 2010 and August
      2014 were identified using the Alberta Provincial Project for Outcome Assessment
      in Coronary Heart Disease registry. Patients with initial LV dysfunction (LVEF
      <40% with first MI or <45% with multiple MI events) underwent a protocol-driven
      repeat LVEF assessment in follow-up if routine LVEF reassessment was not
      performed. RESULTS: Of 5,964 MI patients, follow-up LVEF assessments were
      attained for 442 of the 695 patients who had significant LV dysfunction. A
      sizable proportion (25%) had either no increase or a decline in LVEF. Adverse
      remodeling was associated with an anterior MI location, a greater peak serum
      troponin T, and a higher baseline LVEF at time of MI. Adverse LV remodeling
      conferred a 3-fold risk of death (hazard ratio 3.0, 95% CI 1.6-5.7, P=.001)
      adjusted for baseline LVEF, anterior MI location, and medication use.
      CONCLUSIONS: Current practice of LVEF reassessment during the convalescent months
      post-MI is suboptimal despite a sizeable proportion of patients that undergo
      adverse LV remodeling. Targeting processes affecting low rates of LVEF
      reassessment may reduce missed care opportunities and ensure that patients
      consistently receive appropriate evidence-based and guideline-recommended care.

PMID- 29653654
TI  - Hospital evaluation of health literacy and associated outcomes in patients after
      acute myocardial infarction.
AB  - BACKGROUND: Low health literacy is common in the United States and may affect
      outcomes after myocardial infarction (MI). How often hospitals screen for low
      health literacy is unknown. METHODS: We surveyed 122 hospitals in the TRANSLATE
      ACS study and divided them into those that reported routinely (>75% of patients),
      selectively (1%-75%), or never (0%) screening MI patients for low health literacy
      prior to discharge. We performed logistic regression with random intercepts to
      compare 6-week and 6-month patient-reported medication adherence and
      multivariable Cox regression to compare 1-year major adverse cardiovascular
      events and all-cause readmission risks between hospital groups. RESULTS: Overall,
      25 (20.5%), 47 (38.5%), and 50 (41.0%) hospitals reported routinely, selectively,
      or never screening patients for low health literacy, respectively. Patients
      discharged from hospitals that routinely screened were more likely to report 6
      week medication adherence [routinely: adjusted odds ratio (OR) 1.26, 95% CI 1.01
      1.57; selectively: adjusted OR 1.19, 95% CI 1.00-1.43, both referenced to those
      discharged from hospitals that never screened]. Compared with hospitals that
      never screened health literacy, 1-year major adverse cardiovascular events were
      similar for hospitals that reported routinely screening (adjusted HR 0.92, 95% CI
      0.75-1.14) or selectively screening (adjusted HR 1.01, 95% CI 0.84-1.21).
      Hospitals that reported selectively screening health literacy were associated
      with a lower adjusted risk of 1-year all-cause readmission (adjusted HR 0.89, 95%
      CI 0.79-1.00, P=.041). CONCLUSION: Only a minority of US hospitals routinely
      screen MI patients for low health literacy. Hospital screening was associated
      with higher medication adherence and lower readmission risk. Further
      investigation is needed to understand how inpatient screening can be implemented
      to improve longitudinal post-MI care.

PMID- 29653655
TI  - Straight deep hypothermic circulatory arrest: Should we definitively give up or
      should we keep on?

PMID- 29653656
TI  - Data support continued role for straight deep hypothermic circulatory arrest.

PMID- 29653657
TI  - Clampless facilitated anastomosis with HEARSTRING to reduce cerebral damage
      during off-pump coronary bypass grafting. Don't forget it: Easy to use!

PMID- 29653658
TI  - Use of clampless facilitating devices in patients with low-grade aortic disease:
      is the cost justified by the theoretic risk reduction?

PMID- 29653659
TI  - A tug on the heartstrings.

PMID- 29653660
TI  - Readmission rates: Haven't I seen you somewhere before?

PMID- 29653661
TI  - Pulmonem et pectus.

PMID- 29653662
TI  - Is parameter T staging influenced by tumor behavior?

PMID- 29653663
TI  - New era defining a novel clinical T staging in non-small cell lung cancer.

PMID- 29653664
TI  - We are on the slope together.

PMID- 29653665
TI  - Intraoperative extracorporeal membrane oxygenation and the possibility of
      postoperative prolongation improve survival in bilateral lung transplantation.
AB  - OBJECTIVES: The value of intraoperative extracorporeal membrane oxygenation
      (ECMO) in lung transplantation remains controversial. In our department, ECMO has
      been used routinely for intraoperatively unstable patients for more than 15
      years. Recently, we have extended its indication to a preemptive application in
      almost all cases. In addition, we prolong ECMO into the early postoperative
      period whenever graft function does not meet certain quality criteria or in
      patients with primary pulmonary hypertension. The objective of this study was to
      review the results of this strategy. METHODS: All standard bilateral lung
      transplantations performed between January 2010 and June 2016 were included in
      this single-center, retrospective analysis. Patients were divided into 3 groups:
      group I-no ECMO (n = 116), group II-intraoperative ECMO (n = 343), and group III
      intraoperative and prolonged postoperative ECMO (n = 123). The impact of
      different ECMO strategies on primary graft function, short-term outcomes, and
      patient survival were analyzed. RESULTS: The use of intraoperative ECMO was
      associated with improved 1-, 3-, and 5-year survival compared with non-ECMO
      patients (91% vs 82%, 85% vs 76%, and 80% vs 74%; log-rank P = .041). This effect
      was still evident after propensity score matching of both cohorts. Despite the
      high number of complex patients in group III, outcome was excellent with higher
      survival rates than in the non-ECMO group at all time points. CONCLUSIONS:
      Intraoperative ECMO results in superior survival when compared with
      transplantation without any extracorporeal support. The concept of prophylactic
      postoperative ECMO prolongation is associated with excellent outcomes in
      recipients with pulmonary hypertension and in patients with questionable graft
      function at the end of implantation.

PMID- 29653666
TI  - Cysticercosis-rare but important.

PMID- 29653667
TI  - A review on wetting and water condensation - Perspectives for CO2 condensation.
AB  - Liquefaction of vapor is a necessary, but energy intensive step in several
      important process industries. This review identifies possible materials and
      surface structures for promoting dropwise condensation, known to increase
      efficiency of condensation heat transfer. Research on superhydrophobic and
      superomniphobic surfaces promoting dropwise condensation constitutes the basis of
      the review. In extension of this, knowledge is extrapolated to condensation of
      CO2. Global emissions of CO2 need to be minimized in order to reduce global
      warming, and liquefaction of CO2 is a necessary step in some carbon capture,
      transport and storage (CCS) technologies. The review is divided into three main
      parts: 1) An overview of recent research on superhydrophobicity and promotion of
      dropwise condensation of water, 2) An overview of recent research on
      superomniphobicity and dropwise condensation of low surface tension substances,
      and 3) Suggested materials and surface structures for dropwise CO2 condensation
      based on the two first parts.

PMID- 29653668
TI  - Almost one-half of cracked posterior teeth were symptomatic, and pain to cold was
      the most common finding.

PMID- 29653669
TI  - Hall technique probably has higher success rates than a nonrestorative treatment
      or conventional restorations in primary molars with carious lesions.

PMID- 29653670
TI  - Benefits of implementing pain-related disability and psychological assessment in
      dental practice for patients with temporomandibular pain and other oral health
      conditions.
AB  - BACKGROUND: Evidence in the field of dentistry has demonstrated the importance of
      pain-related disability and psychological assessment in the development of
      chronic symptoms. The Diagnostic Criteria for Temporomandibular Disorders offer a
      brief assessment for the diagnostic process in patients with orofacial pain (Axis
      II). The authors describe relevant outcomes that may guide general oral health
      care practitioners toward tailored treatment decisions and improved treatment
      outcomes and provide recommendations for the primary care setting. METHODS: The
      authors conducted a review of the literature to provide an overview of knowledge
      about Axis II assessment relevant for the general oral health care practitioner.
      RESULTS: The authors propose 3 domains of the Axis II assessment to be used in
      general oral health care: pain location (pain drawing), pain intensity and
      related disability (Graded Chronic Pain Scale [GCPS]), and psychological distress
      (Patient Health Questionnaire-4 [PHQ-4]). In the case of localized pain, low GCPS
      scores (0-II), and low PHQ-4 scores (0-5), patients preferably receive treatment
      in primary care. In the case of widespread pain, high GCPS scores (III-IV), and
      high PHQ-4 scores (6-12), the authors recommend referral to a multidisciplinary
      team, especially for patients with temporomandibular disorder (TMD) pain.
      CONCLUSIONS: The authors recommend psychological assessment at first intake of a
      new adult patient or for patients with persistent TMD pain. The authors recommend
      the pain-related disability screening tools for all TMD pain symptoms and for
      dental pain symptoms that persist beyond the normal healing period. PRACTICAL
      IMPLICATIONS: A brief psychological and pain-related disability assessment for
      patients in primary care may help the general oral health care practitioner make
      tailored treatment decisions.

PMID- 29653672
TI  - Antibiotic oral pack was effective in reducing the rate of oronasal fistula in
      patients undergoing cleft palatoplasty.

PMID- 29653671
TI  - Membrane exposure may decrease the benefits of guided bone regeneration on bone
      levels in the short term.

PMID- 29653673
TI  - [Deep alkali burns: Evaluation of a two-step surgical strategy].
AB  - INTRODUCTION: Chemical burns are rare but often lead to deep cutaneous lesions.
      Alkali agents have a deep and long lasting penetrating power, causing burns that
      evolve over several days. The local treatment for these patients is excision of
      the wound and split thickness skin graft. Early excision and immediate skin
      grafting of alkali burns are more likely to be complicated by graft failure and
      delayed wound healing. We propose a two-step method that delays skin grafting
      until two-three days after burn wound excision. RESULTS: Our population included
      25 controls and 16 cases. Men were predominant with a mean age of 41.9 years. In
      78% of cases, burns were located on the lower limbs. The mean delay between the
      burn and excision was 16.5 days. In cases, the skin graft was performed at a mean
      of 11.3 days after the initial excision. We did not unveil any significant
      difference between both groups for the total skin surface affected, topography of
      the burns and the causal agent. Wound healing was significantly shorter in cases
      vs controls (37.5 days vs 50.3 days; P<0.025). Furthermore, we observed a
      decreased number of graft failures in cases vs controls (13.3% vs 46.7%;
      P=0.059). CONCLUSION: Our study shows the relevance of a two-step surgical
      strategy in patients with alkali chemical burns. Early excision followed by
      interval skin grafting is associated with quicker wound healing and decreased
      rate of graft failure.

PMID- 29653674
TI  - Driving behaviour while self-regulating mobile phone interactions: A human
      machine system approach.
AB  - Mobile phone distracted driving is a recurrent issue in road safety worldwide.
      Recent research on driving behaviour of distracted drivers suggests that in
      certain circumstances drivers seem to assume safer behaviours while using a
      mobile phone. Despite a high volume of research on this topic, self-regulation by
      mobile phone distracted drivers is not well understood as many driving simulator
      experiments are designed to impose an equal level of distraction to participants
      being tested for their driving performance. The aim of this research was to
      investigate the relationship between self-regulatory secondary task performance
      and driving. By a driving simulator experiment in which participants were allowed
      to perform their secondary tasks whenever they feel appropriate, the driving
      performance of 35 drivers aged 18-29 years was observed under three phone
      conditions including non-distraction (no phone use), hands-free interactions and
      visual-manual interactions in the CARRS-Q advanced driving simulator. Drivers'
      longitudinal and lateral vehicle control observed across various road traffic
      conditions were then modelled by Generalized Estimation Equations (GEE) with
      exchangeable correlation structure accounting for heterogeneity resulting from
      multiple observations from the same driver. Results show that the extent of
      engagement in the secondary task influence both longitudinal and lateral control
      of vehicles. Drivers who engaged in a large number of hands-free interactions are
      found to select lower driving speed. In contrast, longer visual-manual
      interactions are found to result in higher driving speed among drivers self
      regulating their secondary task. Among the road traffic conditions, drivers
      distracted by their self-regulated secondary tasks are found to select lower
      speeds along the s-curve compared to straight and motorway segments. In summary,
      the applied human-machine system approach suggests that road traffic demands play
      a vital role in both secondary task management and driving performance.

PMID- 29653675
TI  - Dangerous intersections? A review of studies of fatigue and distraction in the
      automated vehicle.
AB  - The impacts of fatigue on the vehicle driver may change with technological
      advancements including automation and the increasing prevalence of potentially
      distracting in-car systems. This article reviews the authors' simulation studies
      of how fatigue, automation, and distraction may intersect as threats to safety.
      Distinguishing between states of active and passive fatigue supports
      understanding of fatigue and the development of countermeasures. Active fatigue
      is a stress-like state driven by overload of cognitive capabilities. Passive
      fatigue is produced by underload and monotony, and is associated with loss of
      task engagement and alertness. Our studies show that automated driving reliably
      elicits subjective symptoms of passive fatigue and also loss of alertness that
      persists following manual takeover. Passive fatigue also impairs attention and
      automation use in operators of Remotely Piloted Vehicles (RPVs). Use of in
      vehicle media has been proposed as a countermeasure to fatigue, but such media
      may also be distracting. Studies tested whether various forms of phone-based
      media interacted with automation-induced fatigue, but effects were complex and
      dependent on task configuration. Selection of fatigue countermeasures should be
      guided by an understanding of the form of fatigue confronting the operator.
      System design, regulation of level of automation, managing distraction, and
      selection of fatigue-resilient personnel are all possible interventions for
      passive fatigue, but careful evaluation of interventions is necessary prior to
      deployment.

PMID- 29653676
TI  - Financial and recovery worry one year after traumatic injury: A prognostic,
      registry-based cohort study.
AB  - BACKGROUND: Levels of stress post-injury, especially after compensable injury,
      are known to be associated with worse long-term recovery. It is therefore
      important to identify how, and in whom, worry and stress manifest post-injury.
      This study aimed to identify demographic, injury, and compensation factors
      associated with worry about financial and recovery outcomes 12 months after
      traumatic injury. METHODS: Participants (n = 433) were recruited from the
      Victorian Orthopaedic Trauma Outcomes Registry and Victorian State Trauma
      Registry after admission to a major trauma hospital in Melbourne, Australia.
      Participants completed questionnaires about pain, compensation experience and
      psychological wellbeing as part of a registry-based observational study. RESULTS:
      Linear regressions showed that demographic and injury factors accounted for 11%
      and 13% of variance in financial and recovery worry, respectively. Specifically,
      lower education, discharge to inpatient rehabilitation, attributing fault to
      another and having a compensation claim predicted financial worry. Worry about
      recovery was only predicted by longer hospital stay and attributing fault to
      another. In all participants, financial and recovery worry were associated with
      worse pain (severity, interference, catastrophizing, kinesiophobia, self
      efficacy), physical (disability, functioning) and psychological (anxiety,
      depression, PTSD, perceived injustice) outcomes 12 months post-injury. In
      participants who had transport (n = 135) or work (n = 22) injury compensation
      claims, both financial and recovery worry were associated with sustaining
      permanent impairments, and reporting negative compensation system experience 12
      months post-injury. Financial worry 12 months post-injury was associated with not
      returning to work by 3-6 months post-injury, whereas recovery worry was
      associated with attributing fault to another, and higher healthcare use at 6-12
      months post-injury. CONCLUSIONS: These findings highlight the important
      contribution of factors other than injury severity, to worry about finances and
      recovery post-injury. Having a compensation claim, failure to return to work and
      experiencing pain and psychological symptoms also contribute to elevated worry.
      As these factors explained less than half of the variance in worry, however,
      other factors not measured in this study must play a role. As worry may increase
      the risk of developing secondary mental health conditions, timely access to
      financial, rehabilitation and psychological supports should be provided to people
      who are not coping after injury.

PMID- 29653677
TI  - Longevity, Metabolic Disease, and Community Health.
AB  - In the United States, the average lifespan has increased despite the dramatic
      increase in obesity, diabetes, and other conditions that worsen during aging. As
      the longevity of US population increases, it is critical to understand the
      factors that impact aging populations especially as age-related disease and
      declining health becomes more prevalent. Diabetes related to obesity has become
      much more prevalent throughout the United States and globally. Further, the
      prevalence of age-related health problems accelerate in lower income communities
      with less access to health care. All these factors become critical as individuals
      age. Furthermore, in communities with less availability to health care, diagnosis
      may be delayed and treatments are initiated at a much later stage in disease. As
      such, the costs of medical care skyrocket leading to higher costs both to the
      community and to taxpayers. This chapter reviews some key health problems and
      issues in community health and healthy aging, recognizing the importance of
      organizations and programs that provide education and support to the aging
      population. Finally, cultural differences in approaches to healthy aging provide
      important insights and lessons for optimizing quality of life during aging.

PMID- 29653678
TI  - A Comparative Approach to Metabolic Aspects of Aging: Conserved Mechanisms and
      Effects of Calorie Restriction and Environment.
AB  - Metabolic systems and the function of these systems are complex, involving
      biochemical pathways, endocrine, neuroendocrine systems, and physiological
      systems and interact with environmental conditions. Studies in animal models have
      been invaluable in gaining an understanding of the mechanisms involved in
      metabolic endocrine changes during normal aging and with conditions, such as
      diabetes and obesity. Together, these studies have revealed some conserved
      mechanisms and identified specific biomarkers of aging related to metabolic
      changes. Further, characterization of these mechanisms provides an opportunity to
      develop interventions and treatments for both humans and other vertebrates. This
      chapter will provide an overview of age-related changes in metabolism from
      studies in human populations and the perspective of information gained from
      comparative animal models. Detailed molecular mechanisms and endocrine pathways
      have already been discussed in other chapters of this volume. Finally, calorie
      restriction (CR) has shown consistent benefit to age-related disease incidence
      with effects that has been consistent across animal models These studies on the
      effects of CR enable further discernment of disease versus healthy aging
      processes.

PMID- 29653679
TI  - Metabolic Aspects of Aging.
AB  - Metabolic interventions involving undernutrition but not malnutrition (e.g.,
      caloric restriction, CR) are effective strategies for improving both health and
      longevity in species ranging from lower organisms to nonhuman primates. Initial
      human trials to test the effects of sustained, reduced energy intake have yielded
      promising health benefits. Through intense research efforts in understanding the
      molecular mechanisms of CR, three cellular pathways have now been identified
      although the precise details remain unknown. More recently, circadian regulation
      has been recognized as a novel mediator for CR effects in mice. Harnessing the
      molecular insights into CR, novel nutritional interventions and pharmacological
      application of CR mimetics have been tested showing great promise in
      simultaneously improving metabolic function and providing overall health
      benefits. Additional research is needed to identify efficacious therapeutics that
      can be safely and practically translated to human studies in promoting
      healthspan.

PMID- 29653680
TI  - Obesity, Metabolism, and Aging: A Multiscalar Approach.
AB  - Obesity contributes to the aging process through the alteration of metabolic
      pathways evidenced biochemically in the relationship between caloric restriction
      and longevity. Humans have entered into an era of metabolism and aging entirely
      unprecedented in their evolution, with a diet that, for many, contains a majority
      of calories as sugar and yields an expected lifespan of over 80years in
      industrialized nations. Deeply embedded in the complex issue of obesity are
      questions of behavior, causality versus correlation, and appropriate models. For
      example, are primates a better reference than mice for studying metabolic
      connections between obesity and aging? We consider those issues from the
      standpoint of life-history theory, especially implications of the interplay of
      refined sugar and socioeconomic disparities for the future of human health.

PMID- 29653681
TI  - The Intersection of Curandismo and Western Medicine and Their Epidemiological
      Impact for Aging Mexican Americans.
AB  - : The rising costs of health care in the United States continue to stimulate
      interest in alternative health care options among Americans. Western medicine is
      also beginning to pay more attention to these alternative practices and their
      utility for successful treatment of illness. Alternative health care practices
      have always been used by Hispanics whose mortality and morbidity profiles have
      stimulated interest from researchers. Though Hispanics occupy some of the lowest
      socioeconomic positions in the United States, they have higher life expectancy
      rates and comparable rates of morbidity for many health conditions relative to
      other racial/ethnic groups. This has been referred to as the "Hispanic health
      advantage" and the "Hispanic health paradox" [Turra CM, Elo IT. The impact of
      salmon bias on hispanic mortality advantage: new evidence from social security
      data. Popul Res Policy Rev. 2008;27:515. Franzini L, Fernandez-Esquer ME.
      Socioeconomic, cultural, and personal influences on health outcomes in low income
      Mexican-origin individuals in Texas. Soc Sci Med. 2004;59(8):1629-1646. George M.
      The Mexican-American health paradox: the collective influence of sociocultural
      factors on Hispanic health outcomes. DISCUSSIONS: 2013;9(2):2-3. Gallo LC, Penedo
      FJ, Espinosa de los Monteros K, Argueles W. Resiliency in the face of
      disadvantage: do hispanic cultural characteristics protect health outcomes. J
      Pers. 2009;77(6):1707-1746. Turra CM, Goldman N. Socioeconomic differences in
      mortality among U.S. adults: insights into the Hispanic paradox. J Gerontol.
      2007;62(3):184-192]. Even when controlling for socioeconomic status and
      education, life expectancy for Hispanics is greater than that of whites (CDIC,
      2015). Debate about the causes of this paradox continues and some data indicates
      that the paradox is specific to older Hispanics (i.e., middle and older ages).
      Among Hispanic ethnic groups, this "paradox" has been most salient for Mexican
      Americans, therefore, this chapter focuses on Mexican Americans and the
      intersections of traditional health care practices among Mexican Americans
      (curandismo) with the practice of Western medicine to explore how they combine
      and conflict to impact aging Hispanics in three health areas: diabetes,
      menopause, and dementia.

PMID- 29653682
TI  - The Necessity of Active Muscle Metabolism for Healthy Aging: Muscular Activity
      Throughout the Entire Day.
AB  - There is more need for "a movement-movement" than ever before. The percentage of
      seniors in our population is rising exponentially. Sedentary lifestyles
      throughout the lifespan have become the norm, including inactive youth and a
      sedentary workforce. Preventable chronic diseases caused by sedentary living have
      both lowered the quality of life for those directly affected or their families,
      and have created an unsustainable economic dilemma. In this article, we explain
      that whether it is a sedentary student, worker, or retiree, the most neglected
      but essential facts are as follows. By far, the most potent and rapid way to
      raise the rate of healthy metabolic and cardiovascular processes is through the
      immediate benefits of muscle contractions. Working muscle demands more energy and
      fuel than any other tissue in the body, but during inactivity the metabolic rate
      of muscle is relatively low. Depending on the type of contraction, muscle type,
      and other factors, the local fuel requirements within the working muscle can help
      to manage metabolic risks through a variety of processes, such as blood glucose
      utilization, uptake of unhealthy blood triglycerides, and increased blood flow.
      Given the large amount of time that people spend inactive each day, there is an
      enormous opportunity to raise the bar in optimizing health throughout the entire
      lifespan. Developed correctly, safe and low effort muscular activity can be
      performed for relatively long periods of time each day by the elderly and all
      segments of the population to optimize health and well being during aging.

PMID- 29653683
TI  - Dwarf Mice and Aging.
AB  - Dwarf mice have been studied for many decades, however, the focus of these
      studies shifted in 1996 when it was shown by Brown-Borg and her coworkers that
      Ames dwarf (Prop1df) mice are exceptionally long-lived. Since then, Snell dwarf
      (Pit1dw) and growth hormone receptor knockout (GHR-KO, a.k.a. Laron dwarf) mice
      were also shown to be exceptionally long-lived, presumably due to their growth
      hormone (GH)-deficiency or -resistance, respectively. What is of equal importance
      in these dwarf mice is their extended health span, that is, these animals have a
      longer period of life lived free of frailty and age-related diseases. This review
      article focuses on recent studies conducted in these dwarf mice, which concerned
      brown and white adipose tissue biology, microRNA (miRNA) profiling, as well as
      early-life dietary and hormonal interventions. Results of these studies identify
      novel mechanisms linking reduced GH action with extensions of both life span and
      health span.

PMID- 29653685
TI  - Corrigendum to "Hygroscopic behavior of water-soluble matter in marine aerosols
      over the East China Sea" [Sci. Total Environ. 578 (2017) 307-316].

PMID- 29653684
TI  - Cellular Metabolism and Aging.
AB  - Metabolic changes are hallmarks of aging and genetic and pharmacologic
      alterations of relevant pathways can extend life span. In this review, we will
      outline how cellular biochemistry and energy homeostasis change during aging. We
      will highlight protein quality control, mitochondria, epigenetics, nutrient
      sensing pathways, as well as the interplay between these systems with respect to
      their impact on cellular health.

PMID- 29653686
TI  - Pegvaliase for the treatment of phenylketonuria: Results of a long-term phase 3
      clinical trial program (PRISM).
AB  - BACKGROUND: Phenylketonuria (PKU) is caused by phenylalanine hydroxylase (PAH)
      deficiency that results in phenylalanine (Phe) accumulation. Pegvaliase,
      PEGylated recombinant Anabaena variabilis phenylalanine ammonia lyase (PAL),
      converts Phe to trans-cinnamic acid and ammonia, and is a potential enzyme
      substitution therapy to lower blood Phe in adults with PKU. METHODS: Two Phase 3
      studies, PRISM-1 and PRISM-2, evaluated the efficacy and safety of pegvaliase
      treatment using an induction, titration, and maintenance dosing regimen in adults
      with PKU. In PRISM-1, pegvaliase-naive participants with blood Phe >600 MUmol/L
      were randomized 1:1 to a maintenance dose of 20 mg/day or 40 mg/day of
      pegvaliase. Participants in PRISM-1 continued pegvaliase treatment in PRISM-2, a
      4-part clinical trial that includes an ongoing, open-label, long-term extension
      study of pegvaliase doses of 5 mg/day to 60 mg/day. RESULTS: Of 261 participants
      who received pegvaliase treatment, 72.0% and 32.6% reached >=12 months and >= 24
      months of study treatment, respectively, and 65% are still actively receiving
      treatment. Mean (SD) blood Phe was 1232.7 (386.4) MUmol/L at baseline, 564.5
      (531.2) MUmol/L at 12 months, and 311.4 (427) MUmol/L at 24 months, a decrease
      from baseline of 51.1% and 68.7%, respectively. Within 24 months, 68.4% of
      participants achieved blood Phe <=600 MUmol/L, 60.7% of participants achieved
      blood Phe <=360 MUmol/L, below the upper limit recommended in the American
      College of Medical Genetics and Genomics PKU management guidelines, and 51.2%
      achieved blood Phe <=120 MUmol/L, below the upper limit of normal in the
      unaffected population. Improvements in neuropsychiatric outcomes were associated
      with reductions in blood Phe and were sustained with long-term pegvaliase
      treatment. Adverse events (AEs) were more frequent in the first 6 months of
      exposure (early treatment phase) than after 6 months of exposure (late treatment
      phase); 99% of AEs were mild or moderate in severity and 96% resolved without
      dose interruption or reduction. The most common AEs were arthralgia (70.5%),
      injection-site reaction (62.1%), injection-site erythema (47.9%), and headache
      (47.1%). Acute systemic hypersensitivity events consistent with clinical National
      Institute of Allergy and Infectious Diseases and the Food Allergy and Anaphylaxis
      Network anaphylaxis criteria were observed in 12 participants (17 events); of
      these, 6 participants remained on treatment. Acute systemic hypersensitivity
      events including potential events of anaphylaxis were not associated with
      immunoglobulin E, and all events resolved without sequelae. CONCLUSION: Results
      from the PRISM Phase 3 program support the efficacy of pegvaliase for the
      treatment of adults with PKU, with a manageable safety profile in most
      participants. The PRISM-2 extension study will continue to assess the long-term
      effects of pegvaliase treatment.

PMID- 29653687
TI  - Implementation of a quality improvement project for universal genetic testing in
      women with ovarian cancer.
AB  - OBJECTIVE: The National Comprehensive Cancer Network recommends all women with
      ovarian cancer be offered genetic testing. Despite a decade of endorsement, many
      oncology practitioners have yet to make this a part of routine practice. Referral
      to genetic counseling and completion of genetic testing among patients at
      substantial risk of germline mutations are significantly lacking, adversely
      affecting patient care and squandering an opportunity to maximize cancer
      prevention efforts. This project determined the impact and feasibility of
      implementing a basic model for universal referral to genetic counseling and
      completion of genetic testing in women with a diagnosis of ovarian cancer in an
      academic gynecology oncology practice with access to electronic health records
      (EHRs). METHODS: Patients diagnosed with ovarian cancer from January 2008 to
      November 2013 were retrospectively reviewed to determine the baseline referral
      rate for genetic counseling and testing completion in our practice.
      Implementation of a process change model combining provider training, patient
      education, enhanced electronic health record documentation and improved patient
      appointment scheduling strategies were implemented. We then prospectively
      collected data on all newly diagnosed ovarian cancer patients that had not
      already undergone genetic testing presenting from December 1, 2013 to November
      30, 2016. RESULTS: Genetic referral rates, genetic counseling and testing
      completion rates were markedly improved. Pre-implementation our genetic testing
      rate was 27% and post implementation our testing rate was 82% (p-value<=0.001).
      CONCLUSIONS: Low cost interventions that target education of both providers and
      patients regarding the importance of genetic testing along with utilization of
      the EHR and streamlined patient appointment services can significantly increase
      rates of genetic testing completion.

PMID- 29653688
TI  - Evaluation and suggestions for improving the FIGO 2000 staging criteria for
      gestational trophoblastic neoplasia: A ten-year review of 1420 patients.
AB  - BACKGROUND: To re-evaluate the efficacy of the prognostic factors currently
      employed in the treatment of malignant gestational trophoblastic neoplasia.
      METHODS: Clinical data from the Gestational Trophoblastic Disease (GTD) Center at
      Peking Union Medical Hospital (PUMCH) collected between January 2002 and December
      2013 were retrospectively analyzed. Univariate and multivariate analyses of
      prognostic factors were performed using the Cox proportional hazards model. A new
      hazard ratio (HR)-based prognostic scoring scale was established and compared
      with the original scoring system. RESULTS: In total, 1420 cases were included in
      the study (median follow-up=40months, overall complete remission (CR) rate=95.8%,
      relapse rate=7.1%, mortality rate=5.5%, median disease-free survival
      (DFS)=36months). Low-risk (0-6 points) and high-risk (>=6 points) patients
      exhibited CR rates of 99.8% (915/917) and 88.5% (445/503) and mortality rates of
      0.3% and 15.1% (P<0.001), respectively. Univariate and multivariate analyses
      showed that age, pretreatment serum levels of human chorionic gonadotropin beta
      subunit (beta-hCG) and maximum tumor diameter were not independent prognostic
      risk factors. Antecedent pregnancy, the interval from the index pregnancy, the
      number of metastases and a history of failed chemotherapy treatments were
      independent prognostic risk factors. By modifying the scoring system based on the
      variables identified in a Cox analysis, we significantly increased the area under
      the receiver operating characteristics (ROC) curve. CONCLUSION: Though effective,
      the accuracy of the International Federation of Gynecology and Obstetrics (FIGO)
      2000 Trophoblastic Neoplasia Staging System requires improvement. Irrelevant
      prognostic factors should be removed, and the weights of other factors should be
      adjusted appropriately.

PMID- 29653689
TI  - LPS enhances platelets aggregation via TLR4, which is related to mitochondria
      damage caused by intracellular ROS, but not extracellular ROS.
AB  - Platelet is an important cell contributing to hemostasis and immunity. Bacterial
      lipopolysaccharide (LPS), mainly functioning by stimulating toll-like receptor 4
      (TLR4), mediates platelet activation and sepsis. However, the inter-relationship
      between these players in sepsis remains unknown. We found that the aggregation of
      platelets was enhanced in complete blood of sepsis patients than that of healthy
      donors. PRP isolated from complete blood of healthy donors was used in the
      following study to filter out the interference of irrelevant cells. The results
      shown that the maximum aggregation rate (MAR) was significantly higher in LPS
      challenged PRP model than that of controls, and administration of the specific
      TLR4 inhibitor, TAK242, reduced the MAR in this model. LPS promoted P-selectin
      expression and intracellular ROS production, and both TAK242 and N-acetyl-L
      cysteine (NAC) could depressed the LPS-induced increase of P-selectin and
      intracellular ROS. H2O2 administration increased P-selectin expression partially
      but had little effect on intracellular ROS, thought it increased mitochondrial
      damage. In vivo, LPS increased both intracellular ROS and CD62P comparing with
      that of controls, effects that were prevented by TAK242. Furthermore, platelet
      aggregation through LPS-TLR4 pathway was involved in AKT, PKC and p38
      phosphorylation but not cGMP/cAMP pathway. In conclusion, this study shows that
      intracellular ROS, not extracellular ROS such as H2O2, plays a crucial role in
      facilitating platelet aggregation via LPS/TLR4 pathway, and this process was
      involved in AKT, PKC and p38 phosphorylation but not cGMP/cAMP pathway. The
      results would helpful for understanding the role of intracellular ROS and LPS
      TLR4 pathway in platelet aggregation.

PMID- 29653690
TI  - Protective efficacy of a plasmid DNA vaccine against transgene-specific tumors by
      Th1 cellular immune responses after intradermal injection.
AB  - With DNA vaccines, it is important to monitor the movement of transfectants and
      to overcome immune deviations. We used a pCMV-LacZ plasmid (expressing beta
      galactosidase) and a pcDNA-hNIS plasmid (expressing the human sodium/iodide
      symporter [hNIS] gene) as non-secreted visual-imaging markers. Transfectants
      carrying the hNIS or LacZ gene migrated to peripheral lymphoid tissues. hNIS
      expressing cells were observed specifically in the LNs and spleen. Anti-beta
      galactosidase was detected in LacZ DNA immunized mice after boosting twice,
      suggestive of Th2 humoral immune responses. Antibody isotyping defined the
      humoral immune response. A dominant IgG2a type occurred in hNIS-immunized mice in
      ELISAs. IgG2a/IgG1 ratios increased after hNIS DNA vaccination. High levels of
      INF-gamma-secreting cells were identified in ELISpot and increased IFN-gamma
      levels were found in cytokine ELISAs. Tumor growth decreased in hNIS DNA
      immunized mice. In conclusion, humoral immune responses switched to the Th1
      cellular immune response, even though we administered plasmid DNA by intra dermal
      injection.

PMID- 29653691
TI  - [Epicapsular stars].

PMID- 29653692
TI  - Model-based analyses of the cesium dynamics in the small mesotrophic reservoir,
      Pond 4. I. Estimating the inventories of and the fluxes among the pond's major
      biotic components.
AB  - A model of cesium (Cs) dynamics among the principal biotic and abiotic components
      of an 11.4-ha impoundment is described. The model is derived from analyses of
      field measurements of Cs-133 concentrations in pond components for 500 days
      following the addition of 4 kg of stable Cs-133 to the system. This study differs
      from similar experiments in which radionuclides, or their stable analogs have
      been added to small ponds in that the biomasses of key pond components were also
      obtained. The Cs-133 concentrations and biomasses were used to compute the
      dynamics of Cs-133 inventories and fluxes among the pond components. The model
      permits interesting comparisons of Cs-133 transport and fate over time among the
      pond's abiotic components, primary producers, and two-orders of consumers. The
      importance of the submerged macrophyte and periphyton community in controlling
      the transport and fate of the added Cs-133 is quantified. Macrophytes intercepted
      much of the Cs-133 and slowed its ultimate sequestration by the sediments. The
      macrophytes' rapid absorption and slow release of Cs-133 prolonged the
      availability of the element to other pond biota. These data are being used within
      a subsequent paper to further develop the model into one in which the Cs-133
      kinetics are described by transfer coefficients so that effects of changing
      environmental variables and remediation options can be explored.

PMID- 29653693
TI  - Four years follow up of ACY1 deficient patient and pedigree study.
AB  - Aminoacylase 1 deficiency (ACY1D) is a rare inborn error of metabolism
      characterized by increased urinary excretion of N-acetylated amino acids.
      Clinical phenotypes of 15 known patients with ACY1 deficiency have been described
      up to now. Findings are greatly variable, ranging from normality to relevant
      neurological and psychiatric impairments, but clinical follow up has been rarely
      reported. To partially fill this gap, we present a detailed clinical description
      and the outcome four years post-diagnosis of a patient already described, with
      mild intellectual disability, language delay, autistic traits and compound
      heterozygous mutations in ACY1.

PMID- 29653694
TI  - Trophic transfer of microplastics and mixed contaminants in the marine food web
      and implications for human health.
AB  - Plastic litter has become one of the most serious threats to the marine
      environment. Over 690 marine species have been impacted by plastic debris with
      small plastic particles being observed in the digestive tract of organisms from
      different trophic levels. The physical and chemical properties of microplastics
      facilitate the sorption of contaminants to the particle surface, serving as a
      vector of contaminants to organisms following ingestion. Bioaccumulation factors
      for higher trophic organisms and impacts on wider marine food webs remain
      unknown. The main objectives of this review were to discuss the factors
      influencing microplastic ingestion; describe the biological impacts of associated
      chemical contaminants; highlight evidence for the trophic transfer of
      microplastics and contaminants within marine food webs and outline the future
      research priorities to address potential human health concerns. Controlled
      laboratory studies looking at the effects of microplastics and contaminants on
      model organisms employ nominal concentrations and consequently have little
      relevance to the real environment. Few studies have attempted to track the fate
      of microplastics and mixed contaminants through a complex marine food web using
      environmentally relevant concentrations to identify the real level of risk. To
      our knowledge, there has been no attempt to understand the transfer of
      microplastics and associated contaminants from seafood to humans and the
      implications for human health. Research is needed to determine bioaccumulation
      factors for popular seafood items in order to identify the potential impacts on
      human health.

PMID- 29653695
TI  - Membrane-attached mammalian cytochromes P450: An overview of the membrane's
      effects on structure, drug binding, and interactions with redox partners.
AB  - Mammalian cytochromes P450 are an important class of enzymes involved in the
      biotransformation of many endo- and exogenous compounds. Cytochrome P450 isoforms
      are attached to the membrane of the endoplasmic reticulum or mitochondria, and
      their catalytic domains move along the membrane surface while being partially
      immersed in the membrane environment. Their active sites are connected to both
      the membrane and cytosolic environments via a complex network of access channels.
      Consequently, they can accept substrates from both environments. The membrane
      also supports the interactions of cytochromes P450 with their redox partners. In
      this review, we provide an overview of current knowledge of the structure,
      flexibility, and interactions with substrates and redox partners of cytochrome
      P450 on membranes, amalgamating information derived from both experiments and
      simulations.

PMID- 29653696
TI  - Manganese Increases the Sensitivity of the cGAS-STING Pathway for Double-Stranded
      DNA and Is Required for the Host Defense against DNA Viruses.
AB  - Manganese (Mn) is essential for many physiological processes, but its functions
      in innate immunity remain undefined. Here, we found that Mn2+ was required for
      the host defense against DNA viruses by increasing the sensitivity of the DNA
      sensor cGAS and its downstream adaptor protein STING. Mn2+ was released from
      membrane-enclosed organelles upon viral infection and accumulated in the cytosol
      where it bound directly to cGAS. Mn2+ enhanced the sensitivity of cGAS to double
      stranded DNA (dsDNA) and its enzymatic activity, enabling cGAS to produce
      secondary messenger cGAMP in the presence of low concentrations of dsDNA that
      would otherwise be non-stimulatory. Mn2+ also enhanced STING activity by
      augmenting cGAMP-STING binding affinity. Mn-deficient mice showed diminished
      cytokine production and were more vulnerable to DNA viruses, and Mn-deficient
      STING-deficient mice showed no increased susceptibility. These findings indicate
      that Mn is critically involved and required for the host defense against DNA
      viruses.

PMID- 29653697
TI  - An Interleukin-25-Mediated Autoregulatory Circuit in Keratinocytes Plays a
      Pivotal Role in Psoriatic Skin Inflammation.
AB  - Psoriasis is a chronic autoinflammatory skin disease. Although interleukin-17,
      derived from lymphocytes, has been shown to be critical in psoriasis, the
      initiation and maintenance of chronic skin inflammation has not been well
      understood. IL-25 (also called IL-17E), another IL-17 family cytokine, is well
      known to regulate allergic responses and type 2 immunity. Here we have shown that
      IL-25, also highly expressed in the lesional skin of psoriasis patients, was
      regulated by IL-17 in murine skin of a imiquimod (IMQ)-induced psoriasis model.
      IL-25 injection induced skin inflammation, whereas germline or keratinocyte
      specific deletion of IL-25 caused resistance to IMQ-induced psoriasis. Via IL
      17RB expression in keratinocytes, IL-25 stimulated the proliferation of
      keratinocytes and induced the production of inflammatory cytokines and
      chemokines, via activation of the STAT3 transcription factor. Thus, our data
      demonstrate that an IL-17-induced autoregulatory circuit in keratinocytes is
      mediated by IL-25 and suggest that this circuit could be targeted in the
      treatment of psoriasis patients.

PMID- 29653699
TI  - Sporadic acute benign calf myositis: Systematic literature review.
AB  - Acute benign calf myositis is a rare infection-associated syndrome presenting
      with calf pain that occurs in epidemics or sporadically. Epidemic cases are
      usually associated with influenza virus type B. Sporadic cases, however, might be
      associated with a large number of microorganisms. Furthermore, during an outbreak
      there is a great alertness that promotes earlier diagnosis. In contrast, there is
      likely a lower awareness regarding the sporadic form, compromising early and
      correct diagnosis. In order to characterize the sporadic form of acute calf
      myositis and increase the knowledge of this condition, we systematically reviewed
      the literature reporting sporadic cases. We identified 72 reports, including 451
      patients, 325 males and 126 females. Sporadic acute benign calf myositis affected
      subjects <=18 years of age (N = 450; 99%), who followed a prodromal flu-like
      illness (N = 411; 91%), presented with pain and tenderness affecting only the
      calves for <=11/2 weeks (N = 441; 99%) and was never complicated by kidney
      involvement. The creatine kinase ratio was >=10 in 310 (70%) out of 444 cases.
      Microbiological studies identified an infectious trigger in 181 cases, mostly
      influenza virus (type B more frequently than type A), Dengue, Ebstein-Barr or
      Parainfluenza virus and Mycoplasma pneumoniae. Sporadic acute benign calf
      myositis is a self-limited condition that can usually be diagnosed on a clinical
      basis. Unlike the epidemic form, many cases are due to microorganisms other than
      influenza virus B or A.

PMID- 29653698
TI  - Progression from latent infection to active disease in dynamic tuberculosis
      transmission models: a systematic review of the validity of modelling
      assumptions.
AB  - Mathematical modelling is commonly used to evaluate infectious disease control
      policy and is influential in shaping policy and budgets. Mathematical models
      necessarily make assumptions about disease natural history and, if these
      assumptions are not valid, the results of these studies can be biased. We did a
      systematic review of published tuberculosis transmission models to assess the
      validity of assumptions about progression to active disease after initial
      infection (PROSPERO ID CRD42016030009). We searched PubMed, Web of Science,
      Embase, Biosis, and Cochrane Library, and included studies from the earliest
      available date (Jan 1, 1962) to Aug 31, 2017. We identified 312 studies that met
      inclusion criteria. Predicted tuberculosis incidence varied widely across studies
      for each risk factor investigated. For population groups with no individual risk
      factors, annual incidence varied by several orders of magnitude, and 20-year
      cumulative incidence ranged from close to 0% to 100%. A substantial proportion of
      modelled results were inconsistent with empirical evidence: for 10-year
      cumulative incidence, 40% of modelled results were more than double or less than
      half the empirical estimates. These results demonstrate substantial disagreement
      between modelling studies on a central feature of tuberculosis natural history.
      Greater attention to reproducing known features of epidemiology would strengthen
      future tuberculosis modelling studies, and readers of modelling studies are
      recommended to assess how well those studies demonstrate their validity.

PMID- 29653700
TI  - Introduction: Continuing story of premature progesterone elevation.
AB  - Since the late 1980s premature progesterone elevation has repeatedly caught the
      attention of investigators, not only for its importance, but also because studies
      have shown differing results and conclusions, constituting an unexplainable
      sequence of doubts and uncertainties. This issue's Views and Reviews section
      seeks to present a sequence of short and complementary papers summarizing the
      whole story and updating the reader on the current information and perspectives
      on premature progesterone elevation.

PMID- 29653701
TI  - Premature progesterone elevation in controlled ovarian stimulation: to make a
      long story short.
AB  - Over the past decades many of us have contributed to the controversy surrounding
      the origins and consequences of premature progesterone elevation during
      controlled ovarian stimulation. In this article, we attempt to retrace the
      progression of information on this complex subject which required reviewing a
      number of publications that often contradicted one another. The definition of
      premature progesterone elevation, the pathophysiological mechanisms underlying
      the high peripheral progesterone levels, and the debated consequences of this
      event on in vitro fertilixation-embryo transfer outcome will be addressed from a
      historical perspective.

PMID- 29653702
TI  - Endocrine mechanisms and assay issues in premature progesterone elevation in
      assisted reproductive technology.
AB  - Progesterone elevation occurring in the late phases of controlled ovarian
      stimulation (COS) has been reported for over 25 years. Yet doubts remain
      regarding the mechanisms at play in this phenomenon and its net consequences on
      assisted reproductive technology outcome, which is known to occur in poor and
      good assisted reproductive technology responders. The pathophysiology of end-COS
      progesterone elevation encountered in gonadotropin-suppressed cycles is different
      from that prevailing at the time of, and just after, ovulation. The different
      divergence in practical consequences of end-COS progesterone elevation led to
      review the progesterone assays developed for measuring progesterone in the luteal
      phase of the menstrual cycle, but commonly used for measuring all forms of
      progesterone elevation.

PMID- 29653703
TI  - Premature progesterone elevation: targets and rescue strategies.
AB  - Progesterone elevation during the late follicular phase of ovarian stimulation
      for in vitro fertilization negatively impacts the assisted reproductive
      technology-outcome. The evidence available supports an advanced endometrial
      maturation and a direct negative effect on its receptivity. On the other hand,
      some retrospective analysis suggests an impairment of oocyte and embryo quality.
      Recent publications confirm that enhanced follicle-stimulating hormone
      stimulation towards the end of the follicular phase of ovarian stimulation is the
      main course of progesterone elevation. A key element in preventing this event is
      the individualization of ovarian stimulation according to the patient's ovarian
      reserve and the adaption of the stimulation dosage during late follicular phase
      according to the patient's response. Additional measures as corticosteroid
      administration, avoidance of prolonged stimulation and cycle segmentation with
      freeze-all-policy can be discussed.

PMID- 29653704
TI  - Time-lapse imaging.

PMID- 29653705
TI  - Time-lapse imaging: clearly useful to both laboratory personnel and patient
      outcomes versus just because we can doesn't mean we should.

PMID- 29653706
TI  - Medicine and architecture: a blueprint.

PMID- 29653707
TI  - Next generation sequencing for preimplantation genetic testing for aneuploidy:
      friend or foe?

PMID- 29653708
TI  - Leveraging real-world data to move toward more personalized fertility treatment.

PMID- 29653709
TI  - Arcuate uterus: a legitimate pathological entity?

PMID- 29653710
TI  - When is recombinant luteinizing hormone supplementation beneficial during ovarian
      stimulation?

PMID- 29653711
TI  - To invade, or to observe, that is the question.

PMID- 29653712
TI  - Is insurance coverage for in vitro fertilization a good thing?

PMID- 29653713
TI  - Assessing new technology: what is best for the patient, the surgeon, and the
      healthcare system.

PMID- 29653714
TI  - Ovulation induction with pulsatile gonadotropin releasing hormone: missing in
      action.

PMID- 29653715
TI  - Androgens and endometrium: new lessons from the corpus luteum via the adrenal
      cortex?

PMID- 29653716
TI  - Optimizing fertility preservation with microscopic onco-testicular sperm
      extraction.

PMID- 29653717
TI  - Recombinant luteinizing hormone supplementation in assisted reproductive
      technology: a systematic review.
AB  - OBJECTIVE: To assess the role of recombinant human LH (r-hLH) supplementation in
      ovarian stimulation for ART in specific subgroups of patients. DESIGN: Systematic
      review. SETTING: Centers for reproductive care. PATIENT(S): Six populations were
      investigated: 1) women with a hyporesponse to recombinant human FSH (r-hFSH)
      monotherapy; 2) women at an advanced reproductive age; 3) women cotreated with
      the use of a GnRH antagonist; 4) women with profoundly suppressed LH levels after
      the administration of GnRH agonists; 5) normoresponder women to prevent ovarian
      hyperstimulation syndrome; and 6) women with a "poor response" to ovarian
      stimulation, including those who met the European Society for Human Reproduction
      and Embryology Bologna criteria. INTERVENTION(S): Systematic review. MAIN OUTCOME
      MEASURE(S): Implantation rate, number of oocytes retrieved, live birth rate,
      ongoing pregnancy rate, fertilization rate, and number of metaphase II oocytes.
      RESULT(S): Recombinant hLH supplementation appears to be beneficial in two
      subgroups of patients: 1) women with adequate prestimulation ovarian reserve
      parameters and an unexpected hyporesponse to r-hFSH monotherapy; and 2) women 36
      39 years of age. Indeed, there is no evidence that r-hLH is beneficial in young
      (<35 y) normoresponders cotreated with the use of a GnRH antagonist. The use of r
      hLH supplementation in women with suppressed endogenous LH levels caused by GnRH
      analogues and in poor responders remains controversial, whereas the use of r-hLH
      supplementation to prevent the development of ovarian hyperstimulation syndrome
      warrants further investigation. CONCLUSION(S): Recombinant hLH can be proposed
      for hyporesponders and women 36-39 years of age.

PMID- 29653718
TI  - Reintervention risk and quality of life outcomes after uterine-sparing
      interventions for fibroids: a systematic review and meta-analysis.
AB  - OBJECTIVES: To compare uterine-sparing treatment options for fibroids in terms of
      reintervention risk and quality of life. DESIGN: Systematic review and meta
      analysis according to PRISMA guidelines. SETTING: Not applicable. PATIENT(S):
      Women with uterine fibroids undergoing a uterine-sparing intervention.
      INTERVENTIONS(S): Not applicable. MAIN OUTCOME MEASURE(S): 1) Reintervention risk
      after uterine-sparing treatment for fibroids after 12, 36, and 60 months; and 2)
      quality of life outcomes, based on validated questionnaires. Two separate
      analyses were performed for the procedures that used an abdominal approach
      (myomectomy, uterine artery embolization [UAE], artery ligation, high-intensity
      focused ultrasound [HIFU], laparoscopic radiofrequency ablation [RFA]) and for
      the procedures managing intracavitary fibroids (hysteroscopic approach, including
      hysteroscopic myomectomy and hysteroscopic RFA). RESULT(S): There were 85
      articles included for analysis, representing 17,789 women. Stratified by
      treatment options, reintervention risk after 60 months was 12.2% (95% confidence
      interval [CI] 5.2%-21.2%) for myomectomy, 14.4% (95% CI 9.8%-19.6%) for UAE,
      53.9% (95% CI 47.2%-60.4%) for HIFU, and 7% (95% CI 4.8%-9.5%) for hysteroscopy.
      For the other treatment options, no studies were available at 60 months. For
      quality of life outcomes, symptoms improved after treatment for all options. The
      HIFU procedure had the least favorable outcomes. CONCLUSION(S): Despite the
      substantial heterogeneity of the study population, this meta-analysis provides
      valuable information on relative treatment efficacy of various uterine-sparing
      interventions for fibroids, which is relevant when counseling patients in daily
      practice. Furthermore, this study demonstrates that long-term data, particularly
      for the newest uterine-sparing interventions, are urgently needed.

PMID- 29653719
TI  - Using microscope for onco-testicular sperm extraction for bilateral testis
      tumors.
AB  - OBJECTIVE: To demonstrate a step-by-step approach to the use of the operating
      microscope for onco-testicular sperm extraction. DESIGN: Video presentation.
      SETTING: University hospital. PATIENT(S): A 34-year-old man (status post right
      orchiectomy at another institution for pT3 pure seminoma with negative
      preoperative tumor markers) was referred for contralateral orchiectomy for
      multifocal left testis mass and fertility preservation. A postoperative semen
      analysis for attempted cryopreservation of ejaculated semen identified
      azoospermia. INTERVENTION(S): Left radical orchiectomy, left microsurgical onco
      testicular sperm extraction (TESE). MAIN OUTCOME MEASURE(S): Intraoperative
      technique with commentary highlighting tips for successful fertility preservation
      via microsurgical onco-TESE. Discussion of alternatives. RESULT(S): This video
      provides a step-by-step guide to microsurgical onco-TESE coordinated with radical
      orchiectomy for testis cancer as a means of fertility preservation in an
      azoospermic patient. Preoperative imaging with scrotal ultrasound can serve as a
      useful guide for targeting microdissection to areas of normal testicular
      parenchyma for extraction of seminiferous tubules likely to host normal
      spermatogenesis. This patient had successful recovery and cryopreservation of
      abundant testicular sperm following targeted ex-vivo testicular microdissection.
      CONCLUSION(S): Microsurgical onco-TESE may be offered to azoospermic patients
      when undergoing orchiectomy for testis cancer. Use of preoperative imaging and
      the surgical microscope guide surgical dissection and optimize sperm recovery.

PMID- 29653720
TI  - The ethical and deontological charter of the French faculties of medicine and
      odontology.

PMID- 29653721
TI  - One last Who am I!

PMID- 29653722
TI  - War, Climate Change, and Migration.

PMID- 29653723
TI  - Characterization of the duodenal bacterial microbiota in patients with pancreatic
      head cancer vs. healthy controls.
AB  - An increasing number of reports have demonstrated that there is an association
      between the presence of pathogenic microorganisms and pancreatic cancer. However,
      the role of the duodenal microbiota in pancreatic carcinogenesis remains unknown.
      In this study, duodenal mucosal microbiota was analyzed in 14 patients with
      pancreatic head cancer and 14 healthy controls using 16S rRNA gene pyrosequencing
      methods. Plasma endotoxin activity and the concentrations of the proinflammatory
      cytokine IL-6 and C-reactive protein (CRP) were measured in blood samples. The
      urea breath test was used to detect Helicobacter pylori infections. Endoscopic
      duodenal mucosal biopsies were evaluated by histological examinations.
      Statistical comparisons of inflammatory factors revealed significantly higher
      levels of CRP and IL-6 in the pancreatic cancer group as compared to healthy
      controls. Patients with pancreatic cancer also had a higher incidence of H.
      pylori infections and showed mucosal changes, including villous abnormalities and
      diffuse inflammatory cell infiltration in the lamina propria. The sequences
      analysis showed that based on linear discriminant analysis effect size (LEfSe)
      analysis at the genus level, Acinetobacter, Aquabacterium, Oceanobacillus,
      Rahnella, Massilia, Delftia, Deinococcus, and Sphingobium were more abundant in
      the duodenal mucosa of pancreatic cancer patients, whereas the duodenal
      microbiotas of healthy controls were enriched with Porphyromonas, Paenibacillus,
      Enhydrobacter, Escherichia, Shigella, and Pseudomonas. These results reveal a
      picture of duodenal microbiota in pancreatic head cancer patients that could be
      useful in future trials investigating the role of gut microbiota in pancreatic
      cancer.

PMID- 29653724
TI  - The effect of DLC-coating deposition method on the reliability and mechanical
      properties of abutment's screws.
AB  - OBJECTIVE: To characterize the mechanical properties of different coating methods
      of DLC (diamond-like carbon) onto dental implant abutment screws, and their
      effect on the probability of survival (reliability). METHODS: Seventy-five
      abutment screws were allocated into three groups according to the coating method:
      control (no coating); UMS - DLC applied through unbalanced magnetron sputtering;
      RFPA-DLC applied through radio frequency plasma-activated (n=25/group). Twelve
      screws (n=4) were used to determine the hardness and Young's modulus (YM). A 3D
      finite element model composed of titanium substrate, DLC-layer and a counterpart
      were constructed. The deformation (MUm) and shear stress (MPa) were calculated.
      The remaining screws of each group were torqued into external hexagon abutments
      and subjected to step-stress accelerated life-testing (SSALT) (n=21/group). The
      probability Weibull curves and reliability (probability survival) were calculated
      considering the mission of 100, 150 and 200N at 50,000 and 100,000 cycles.
      RESULTS: DLC-coated experimental groups evidenced higher hardness than control
      (p<0.05). In silico analysis depicted that the higher the surface Young's
      modulus, the higher the shear stress. Control and RFPA showed beta<1, indicating
      that failures were attributed to materials strength; UMS showed beta>1 indicating
      that fatigue contributed to failure. High reliability was depicted at a mission
      of 100N. At 200N a significant decrease in reliability was detected for all
      groups (ranging from 39% to 66%). No significant difference was observed among
      groups regardless of mission. Screw fracture was the chief failure mode.
      SIGNIFICANCE: DLC-coating have been used to improve titanium's mechanical
      properties and increase the reliability of dental implant-supported restorations.

PMID- 29653725
TI  - Numerical fatigue analysis of premolars restored by CAD/CAM ceramic crowns.
AB  - OBJECTIVES: The purpose of this study was to estimate the fatigue life of
      premolars restored with two dental ceramics, lithium disilicate (LD) and polymer
      infiltrated ceramic (PIC) using the numerical method and compare it with the
      published in vitro data. METHODS: A premolar restored with full-coverage crown
      was digitized. The volumetric shape of tooth tissues and crowns were created in
      Mimics(r). They were transferred to IA-FEMesh for mesh generation and the model
      was analyzed with Abaqus. By combining the stress distribution results with
      fatigue stress-life (S-N) approach, the lifetime of restored premolars was
      predicted. RESULTS: The predicted lifetime was 1,231,318 cycles for LD with
      fatigue load of 1400N, while the one for PIC was 475,063 cycles with the load of
      870N. The peak value of maximum principal stress occurred at the contact area
      (LD: 172MPa and PIC: 96MPa) and central fossa (LD: 100MPa and PIC: 64MPa) for
      both ceramics which were the most seen failure areas in the experiment. In the
      adhesive layer, the maximum shear stress was observed at the shoulder area (LD:
      53.6MPa and PIC: 29MPa). SIGNIFICANCE: The fatigue life and failure modes of all
      ceramic crown determined by the numerical method seem to correlate well with the
      previous experimental study.

PMID- 29653726
TI  - Fabrication and characterisation of a novel biomimetic anisotropic
      ceramic/polymer-infiltrated composite material.
AB  - OBJECTIVE: To fabricate and characterise a novel biomimetic composite material
      consisting of aligned porous ceramic preforms infiltrated with polymer. METHOD:
      Freeze-casting was used to fabricate and control the microstructure and porosity
      of ceramic preforms, which were subsequently infiltrated with 40-50% by volume
      UDMA-TEGDMA polymer. The composite materials were then subjected to
      characterisation, namely density, compression, three-point bend, hardness and
      fracture toughness testing. Samples were also subjected to scanning electron
      microscopy and computerised tomography (Micro-CT). RESULTS: Three-dimensional
      aligned honeycomb-like ceramic structures were produced and full interpenetration
      of the polymer phase was observed using micro-CT. Depending on the volume
      fraction of the ceramic preform, the density of the final composite ranged from
      2.92 to 3.36g/cm3, compressive strength ranged from 206.26 to 253.97MPa, flexural
      strength from 97.73 to 145.65MPa, hardness ranged from 1.46 to 1.62GPa, and
      fracture toughness from 3.91 to 4.86MPam1/2. SIGNIFICANCE: Freeze-casting
      provides a novel method to engineer composite materials with a unique aligned
      honeycomb-like interpenetrating structure, consisting of two continuous phases,
      inorganic and organic. There was a correlation between the ceramic fraction and
      the subsequent, density, strength, hardness and fracture toughness of the
      composite material.

PMID- 29653727
TI  - Department of Error.

PMID- 29653728
TI  - Prenatal diagnosis of trisomy 18 rescue resulting in mosaic of two different
      diploid cell lines in a hydropic fetus.

PMID- 29653729
TI  - Circulation of influenza in backyard productive systems in central Chile and
      evidence of spillover from wild birds.
AB  - Backyard productive systems (BPS) are recognized as the most common form of
      animal production in the world. However, BPS frequently exhibit inherent
      biosecurity deficiencies, and could play a major role in the epidemiology of
      animal diseases and zoonoses. The aim of this study was to determine if influenza
      A viruses (IAV) were prevalent in backyard poultry and swine BPS in central
      Chile. Through active surveillance in Valparaiso and Metropolitan regions from
      2012 - 2014, we found that influenza virus positivity by real-time RT-PCR (qRT
      PCR) ranged from 0% during winter 2012-45.8% during fall 2014 at the farm level.
      We also obtained an H12 hemagglutinin (HA) sequence of wild bird origin from a
      domestic Muscovy duck (Cairina moschata), indicating spillover from wild birds
      into backyard poultry populations. Furthermore, a one-year sampling effort in 113
      BPS in the Libertador Bernardo O'Higgins (LGB OHiggins) region showed that 12.6%
      of poultry and 2.4% of swine were positive for IAV by enzyme-linked immunosorbent
      assay (ELISA), indicative of previous exposure of farm animals to IAV. This study
      highlights the need for improved IAV surveillance in backyard populations given
      the close interaction between domestic animals, wild birds and people in these
      farms, particularly in an understudied region, like South America.

PMID- 29653730
TI  - Beliefs, intentions, and beyond: A qualitative study on the adoption of
      sustainable gastrointestinal nematode control practices in Flanders' dairy
      industry.
AB  - Emerging anthelmintic resistance emphasizes the need for sustainable control
      approaches against gastrointestinal nematode (GIN) infections in cattle. The
      uptake of diagnostic methods for sustainable control could enable more informed
      treatments and reduce excessive anthelmintic use. Unfortunately, the adoption of
      such methods remains relatively poor. A better understanding of farmers'
      motivations and behaviour would help to develop applicable advises and
      communication strategies for sustainable worm control strategies. A previous
      study created a general model for adoption intention of GIN diagnostics on dairy
      farms and measured the most important factors driving this intention (Vande Velde
      et al., 2015). The current research aimed to dig deeper into this model for the
      beliefs underlying these factors, and to identify additional factors impelling
      this specific behaviour. Data were collected through 22 semi-structured
      interviews with dairy farmers. Using analytic induction analysis, data were moved
      between deduction and induction. Results show that the adoption process of
      diagnostic methods for GIN occurs through three different phases: adoption
      intention, actual adoption and maintenance. Low infection awareness and low
      priority ('top of mind') of the disease are important barriers for adopting
      sustainable GIN control. Secondly, farmer behaviour is guided by two important
      social norms: the opinion of their veterinarian and their fellow farmers.
      However, farmers hold an incongruent relationship with both norms throughout
      different stages of behaviour: they do not value other farmers' opinions as a
      positive reference (intention phase), but follow and mimic their behaviour as a
      group (action phase). The veterinarian is seen as the most important positive
      reference, but also the responsible actor for GIN control. As such, the farmers
      do not hold themselves responsible for implementing sustainable control
      strategies. Thirdly, different types of motivations influence different sorts of
      behaviours. Sustainable behaviour such as use of diagnostics will be influenced
      by moral motives, while management behaviour such as treatment is raised by more
      economic motives. Finally, not only performing, but also maintaining behaviour is
      important to fully address the adoption of sustainable control. As such, to
      maintain the adoption on farm, planning could be an important contribution. These
      insights can be used by animal health organizations and industry by exploiting
      motivations, social norms and planning to encourage the uptake of diagnostic
      approaches in GIN control.

PMID- 29653731
TI  - Detection of influenza A virus from agricultural fair environment: Air and
      surfaces.
AB  - Agricultural fairs facilitate an environment conducive to the spread of influenza
      A virus with large numbers of pigs from various different locales comingling for
      several days (5-8 days). Fairs are also associated with zoonotic transmission of
      influenza A virus as humans have unrestricted contact with potentially infected
      swine throughout the fair's duration. Since 2005, the Centers for Disease Control
      and Prevention has reported 468 cases of variant influenza A virus, with most
      cases having had exposure to swine at agricultural fairs. Many mechanisms have
      been proposed as potential direct and indirect routes of transmission that may be
      enhancing intra- and inter-species transmission of influenza A virus at fairs.
      This study examines airborne respiratory droplets and portable animal-care items
      as potential routes of transmission that may be contributing to enhanced viral
      spread throughout the swine barn and the resulting variant cases of influenza A.
      Air samples were taken from inside swine barns at 25 fairs between the years 2013
      and 2014. Influenza A virus was detected molecularly in 11 of 59 (18.6%) air
      samples, representing 4 of the 25 fairs. Viable H1N1 virus, matching virus
      recovered from swine at the fair, was recovered from the air at one fair in 2013.
      During the summer of 2016, 75 of 400 (18.8%) surface samples tested positive for
      molecular presence of influenza A virus and represented 10 of 20 fairs. Seven
      viral isolates collected from four fairs were recovered from the surfaces. Whole
      genome sequences of the viruses recovered from the surfaces are >99% identical to
      the viruses recovered from individual pigs at each respective fair. The detection
      and recovery of influenza A virus from both the air and surfaces found within the
      swine barn at agricultural fairs provide evidence for potential viral
      transmission through these routes, which may contribute to both intra- and inter
      species transmission, threatening public health. These findings reinforce the
      need for new and improved mitigation strategies at agricultural fairs in order to
      reduce the risk to animal and public health.

PMID- 29653732
TI  - A longitudinal study of faecal shedding of Yersinia enterocolitica and Yersinia
      pseudotuberculosis by Merino lambs in south-eastern Australia.
AB  - A prospective longitudinal study was conducted to investigate potential risk
      factors for faecal shedding of Yersinia enterocolitica and Y. pseudotuberculosis
      by Merino lambs in four flocks in south-eastern Australia. The primary aims of
      the study were to determine the seasonal patterns of shedding of pathogenic Y.
      enterocolitica and Y. pseudotuberculosis, and to evaluate putative risk factors
      for faecal shedding of these organisms, including worm egg count, live-weight and
      growth rate. The risk of shedding varied markedly between Yersinia spp., farms,
      seasons and years. Shedding of Y. pseudotuberculosis occurred predominately in
      winter, whereas Y. enterocolitica was commonly isolated from faeces throughout
      the year. Moderate to high prevalences of shedding of each organism occurred in
      the absence of outbreaks of yersiniosis. In general, for shedding of Y.
      pseudotuberculosis, animals with moderate or high worm egg counts were at
      increased risk of shedding compared with animals with low worm egg counts. Sheep
      with higher average daily weight gains were at decreased risk of shedding Y.
      enterocolitica but at increased risk of shedding Y. pseudotuberculosis. Live
      weight was not significantly associated with risk of shedding either species.
      This study highlighted that exposure to determinants of shedding Y.
      enterocolitica and Y. pseudotuberculosis differ between farms and over time
      within farms. Shedding is likely influenced by environmental, animal and
      management factors. Our results indicate that different or additional risk
      factors are required for yersiniosis over those that cause faecal shedding of
      Yersinia spp., because moderate to high prevalences of shedding were not always
      associated with outbreaks of clinical disease.

PMID- 29653733
TI  - The prevalence of PCV2 viremia in newborn piglets on four endemically infected
      Dutch sow farms is very low.
AB  - Porcine circovirus type 2 (PCV2) systemic disease is currently considered one of
      the most relevant infectious diseases in swine industry worldwide from an
      economical point of view. Although piglets generally become diseased between 8
      and 16 weeks of age, they can be infected much earlier, even already in utero.
      However, data on the prevalence of PCV2 infection in newborn piglets are very
      variable (lower than 40 up to 82%) and most of the studies have been performed in
      US. In European pig farms, using group-housing systems for gestating sows, a
      different herd PCV2 infection and immunological status may be expected and was
      recently reported in Germany. If that is the current scenario in most European
      farms, strategies to prevent horizontal transmission become essential for the
      control of the infection. The aim of our study was to determine the PCV2
      prevalence in newborn piglets on 4 endemically infected farms in the Netherlands
      under European conditions. Eleven sows and 8 piglets per litter from 4 farms
      selected by their assumed PCV2 endemic infection status were sampled. Plasma from
      piglets was analysed with a PCV2 qPCR and serum from the sows was analysed with a
      commercial circovirus IgG ELSIA, circovirus IgM ELISA and PCV2 qPCR. In none of
      the samples from the piglets PCV2 was detected by the qPCR. None of the samples
      from the sows tested positive in the qPCR and circovirus IgM ELISA. The true- and
      apparent prevalence of IgG at herd and sow level were 0.75 and 0.81 and, 0.30 and
      0.32, respectively, and no statistically significant association with sow parity
      was observed. These results reveal a very low prevalence of PCV2 in newborn
      piglets on endemically infected farms in The Netherlands, opening the opportunity
      of re-evaluation of the control measures applied in these farms.

PMID- 29653734
TI  - Using multi-criteria risk ranking methodology to select case studies for a
      generic risk assessment framework for exotic disease incursion and spread through
      Europe.
AB  - We present a novel approach of using the multi-criteria pathogen prioritisation
      methodology as a basis for selecting the most appropriate case studies for a
      generic risk assessment framework. The approach uses selective criteria to rank
      exotic animal health pathogens according to the likelihood of introduction and
      the impact of an outbreak if it occurred in the European Union (EU). Pathogens
      were evaluated based on their impact on production at the EU level and
      international trade. A subsequent analysis included criteria of relevance to
      quantitative risk assessment case study selection, such as the availability of
      data for parameterisation, the need for further research and the desire for the
      case studies to cover different routes of transmission. The framework
      demonstrated is flexible with the ability to adjust both the criteria and their
      weightings to the user's requirements. A web based tool has been developed using
      the RStudio shiny apps software, to facilitate this.

PMID- 29653735
TI  - Development of a risk assessment tool for improving biosecurity on pig farms.
AB  - In the present study a risk assessment tool was developed for improving
      biosecurity on pig farms as part of a voluntary program for PRRS control on farms
      located in NE Spain. The arrival of the PRRS virus through different routes was
      estimated based on their likelihood of harbouring the virus and the estimation of
      a score for the probability of introduction. For each possible route of
      introduction or spread within the herds, single or combined biosecurity measures
      aimed at reducing the probability of PRRS virus transmission were selected.
      Results showed that the scores for the probability of introduction and spreading
      were related to a highly variable application of biosecurity measures. The tool
      developed in the present study may be suitable for identifying where efforts
      should be focused in biosecurity actions forming part of disease control
      programs.

PMID- 29653736
TI  - A time-series approach for clustering farms based on slaughterhouse health
      aberration data.
AB  - A large amount of data is collected routinely in meat inspection in pig
      slaughterhouses. A time series clustering approach is presented and applied that
      groups farms based on similar statistical characteristics of meat inspection data
      over time. A three step characteristic-based clustering approach was used from
      the idea that the data contain more info than the incidence figures. A stratified
      subset containing 511,645 pigs was derived as a study set from 3.5 years of meat
      inspection data. The monthly averages of incidence of pleuritis and of pneumonia
      of 44 Dutch farms (delivering 5149 batches to 2 pig slaughterhouses) were
      subjected to 1) derivation of farm level data characteristics 2) factor analysis
      and 3) clustering into groups of farms. The characteristic-based clustering was
      able to cluster farms for both lung aberrations. Three groups of data
      characteristics were informative, describing incidence, time pattern and degree
      of autocorrelation. The consistency of clustering similar farms was confirmed by
      repetition of the analysis in a larger dataset. The robustness of the clustering
      was tested on a substantially extended dataset. This confirmed the earlier
      results, three data distribution aspects make up the majority of distinction
      between groups of farms and in these groups (clusters) the majority of the farms
      was allocated comparable to the earlier allocation (75% and 62% for pleuritis and
      pneumonia, respectively). The difference between pleuritis and pneumonia in their
      seasonal dependency was confirmed, supporting the biological relevance of the
      clustering. Comparison of the identified clusters of statistically comparable
      farms can be used to detect farm level risk factors causing the health
      aberrations beyond comparison on disease incidence and trend alone.

PMID- 29653737
TI  - Random and systematic sampling error when hooking fish to monitor skin fluke
      (Benedenia seriolae) and gill fluke (Zeuxapta seriolae) burden in Australian
      farmed yellowtail kingfish (Seriola lalandi).
AB  - The Australian farmed yellowtail kingfish (Seriola lalandi, YTK) industry monitor
      skin fluke (Benedenia seriolae) and gill fluke (Zeuxapta seriolae) burden by
      pooling the fluke count of 10 hooked YTK. The random and systematic error of this
      sampling strategy was evaluated to assess potential impact on treatment
      decisions. Fluke abundance (fluke count per fish) in a study cage (estimated
      30,502 fish) was assessed five times using the current sampling protocol and its
      repeatability was estimated the repeatability coefficient (CR) and the
      coefficient of variation (CV). Individual body weight, fork length, fluke
      abundance, prevalence, intensity (fluke count per infested fish) and density
      (fluke count per Kg of fish) were compared between 100 hooked and 100 seined YTK
      (assumed representative of the entire population) to estimate potential selection
      bias. Depending on the fluke species and age category, CR (expected difference in
      parasite count between 2 sampling iterations) ranged from 0.78 to 114 flukes per
      fish. Capturing YTK by hooking increased the selection of fish of a weight and
      length in the lowest 5th percentile of the cage (RR = 5.75, 95% CI: 2.06-16.03, P
      value = 0.0001). These lower end YTK had on average an extra 31 juveniles and 6
      adults Z. seriolae per Kg of fish and an extra 3 juvenile and 0.4 adult B.
      seriolae per Kg of fish, compared to the rest of the cage population (P-value <
      0.05). Hooking YTK on the edge of the study cage biases sampling towards the
      smallest and most heavily infested fish in the population, resulting in poor
      repeatability (more variability amongst sampled fish) and an overestimation of
      parasite burden in the population. In this particular commercial situation these
      finding supported that health management program, where the finding of an
      underestimation of parasite burden could provide a production impact on the study
      population. In instances where fish populations and parasite burdens are more
      homogenous, sampling error may be less severe. Sampling error when capturing fish
      from sea cage is difficult to predict. The amplitude and direction of this error
      should be investigated for a given cultured fish species across a range of
      parasite burden and fish profile scenarios.

PMID- 29653738
TI  - Meta-analysis of the efficacy of Leptospira serovar Hardjo vaccines to prevent
      urinary shedding in cattle.
AB  - Leptospirosis is a zoonosis often associated with occupational exposure from
      livestock that can be prevented by animal vaccination. Several trials have
      assessed vaccine efficacy in livestock but there have been no attempts to
      evaluate these trials jointly. This systematic review and meta-analysis aimed to
      estimate vaccine efficacy to prevent urinary shedding of Leptospira serovar
      Hardjo (Hardjo) in cattle. Three databases were used to search for relevant
      papers published from 1980 to 2015 evaluating commercial vaccines to prevent
      urinary shedding of leptospires after artificial conjunctival or natural
      challenge. A total of 1237 articles were initially identified. Eight articles
      containing information from nine trials that assessed vaccine efficacy to prevent
      Hardjo urinary shedding, as per bacteriological culture, were included in the
      meta-analysis. Fixed effects Mantel-Haenszel (MH) and a Bayesian random effects
      meta-analyses were used to estimate the efficacy of vaccination to prevent Hardjo
      shedding in urine. Vaccine efficacy against Hardjo challenge was 88.7% (95% CI
      81.0%-93.2%) in the MH meta-analysis and 89.9% (95% probability interval 80.6%
      94.9%) in the Bayesian random effects meta-analysis. There was no evidence of
      heterogeneity of study results (p = 0.17). The estimated vaccine efficacy to
      prevent urinary shedding of Hardjo in cattle may be sufficient to reduce disease
      incidence in animals and exposure risk of people working in close contact with
      cattle.

PMID- 29653739
TI  - Risk factors for cutaneous myiasis (blowfly strike) in pet rabbits in Great
      Britain based on text-mining veterinary electronic health records.
AB  - Blowfly strike is a devastating and often rapidly fatal disease in rabbits. In
      Great Britain (GB), Lucilia sericata is the primary causative species. Despite
      its severity, there has been minimal investigatory work into the disease in
      rabbits. Here we used text mining to screen electronic health records (EHRs) from
      a large sentinel network of 389 veterinary practices in GB between March 2014 and
      April 2017 for confirmed cases of blowfly strike in rabbits. Blowfly strike was
      identified in 243 of 42,226 rabbit consultations (0.6%), affecting 205 individual
      rabbits. The anatomical site of recorded blowfly strike lesions was
      overwhelmingly the perineal area (n = 109, 52.4%). Less commonly lesions were
      observed affecting other areas of the body (n = 9, 4.3%) and head (n = 8, 3.8%);
      in 83 consultations (39.9%), the affected area was not specified. Of the rabbits
      presenting with blowfly strike, 44.7% were recorded as being euthanized or died.
      A case control study was used to identify risk factors for blowfly strike in this
      population. Whilst sex and neuter status in isolation were not significantly
      associated with blowfly strike, entire female rabbits showed a 3.3 times greater
      odds of being a case than neutered female rabbits. Rabbits five years of age and
      over were more than 3.8 times likely to present for blowfly strike. For every 1 
      degrees C rise in environmental temperature between 4.67  degrees C and 17.68 
      degrees C, there was a 33% increase risk of blowfly strike, with cases peaking in
      July or August. Overall blowfly strike cases started earlier and peaked higher in
      the south of Great Britain. The most northerly latitude studied was at lower risk
      of blowfly strike than the most southerly (OR = 0.50, p < 0.001). There appeared
      to be no significant relationship between blowfly strike in rabbits and either
      the sheep density or rural and urban land coverage types. The results presented
      here can be used for targeted health messaging to reduce the impact of this
      deadly disease for rabbits. We propose that real-time temporal and spatial
      surveillance of the rabbit disease may also help inform sheep control, where the
      seasonal profile is very similar, and where routine surveillance data is also not
      available. Our results highlight the value of sentinel databases based on EHRs
      for research and surveillance.

PMID- 29653740
TI  - Is syndromic data from rural poultry farmers a viable poultry disease reporting
      tool and means of identifying likely farmer responses to poultry disease
      incursion?
AB  - Syndromic surveillance is a well described tool used in developed countries for
      alerting authorities to livestock disease incursions. However, little work has
      been done to evaluate whether this could be a viable tool in countries where
      disease reporting infrastructure and resources is poor. Consequently, a syndrome
      based questionnaire study in Eastern Zambia was designed to gather data on
      previous encounters farmers had with poultry diseases, as well as control
      measures they use to mitigate them. Descriptive statistics and logistic
      regression were used to analyse the data. Farmers reported an overall annual
      disease incidence in rural poultry for eastern Zambia of 31% (90% CI 29-32%).
      Occurrence of poultry disease in the last 12 months was associated with use of
      middlemen to purchase poultry products (p = 0.05, OR = 7.87), poultry products
      sold or given away from the farm (p = 0.01, OR = 1.92), farmers experiencing a
      period with more trade of poultry and its products (p = 0.04, OR = 1.70),
      presence of wild birds near the farm or village (p = 0.00, OR = 2.47) and poultry
      diseases being reported from neighbouring farms or villages (p = 0.00, OR =
      3.12). The study also tentatively identified three poultry diseases (Newcastle
      Disease, Gumboro Disease and Fowl Pox) from the thirty-four disease syndromes
      provided by farmers. Farmers reported an incidence of 27% for Newcastle Disease
      in 2014. When compared with the state veterinary services data which reported
      Newcastle Disease incidence at 9% in 2014, it seems syndromic data obtained from
      farmers may be more sensitive in identifying disease incursion. Thirty-six
      remedies and strategies farmers use to treat and control these diseases were
      revealed. The main control strategy for identified diseases was vaccination and
      the main treatment was unspecified herbs, which warrants further investigation
      and presents an opportunity for further research in ethno-veterinary medicine.
      More still, this study identified chilli, Aloe Vera, garlic onion, moringa, and
      ash as traditional remedies that are commonly being used in Eastern Zambia, and
      which are also used to treat poultry diseases in Zimbabwe and Botswana. Only
      fourteen remedies described are conventionally accepted by veterinarians as
      remedies and disease control measures for poultry diseases. This study shows that
      syndromic data obtained from farmers is a useful disease reporting tool and could
      be used as an effective means of alerting authorities to disease incursion. In
      addition, it shows that these data may give a more accurate estimate of incidence
      for certain diseases than current surveillance methods and could be useful in
      assessing significant risk factors associated with disease occurrence.

PMID- 29653741
TI  - EASL Clinical Practice Guidelines for the management of patients with
      decompensated cirrhosis.

PMID- 29653742
TI  - Neurocognitive correlates of medication-induced addictive behaviours in
      Parkinson's disease: A systematic review.
AB  - Dopaminergic medication can induce severe addictive behaviours (e.g.,
      pathological gambling) in susceptible Parkinson's disease (PD) patients. It is
      still unknown which particular neurocognitive processes become exacerbated or
      dysfunctional in PD patients with addictive behaviours. We sought to
      systematically review the relevant literature to identity potential
      neurocognitive correlates of medication-induced addictive behaviours in PD. We
      framed our review around neurocognitive processes central to four dominant
      accounts of substance addiction: 'aberrant learning', 'incentive sensitization',
      'impulsivity to compulsivity' and 'impaired response inhibition and salience
      attribution'. Searches of the PubMed and Scopus databases were completed on June
      23, 2017. To be included, studies were required to involve: (a) medicated PD
      patients, without a history of deep brain stimulation, with and without addictive
      behaviours; (b) a reward-related or decision-making task; and (c) statistical
      comparison of addictive and non-addictive groups' 'on' medication performance on
      the task(s). Studies were summarised qualitatively with statistically significant
      (p<.05) group differences and effect sizes (Cohen's d) highlighted. 35 studies
      were included. Findings showed that the extant literature is highly
      heterogeneous. The domains of reward and punishment learning, reflection
      impulsivity and disadvantageous decision-making exemplify this. More homogeneity
      exists in domains in which (a) neurocognitive dysfunction is not apparent (motor
      control, cognitive/attentional flexibility and cognitive control) or (b) typical
      neurocognitive processes appear exacerbated by medication (reward motivation and
      choice impulsivity). Future large-scale neurocognitive studies are still required
      to develop our scientific understanding of addictive behaviours in PD and aid
      their clinical treatment and prediction.

PMID- 29653743
TI  - Functional connectivity of the ventral tegmental area and avolition in subjects
      with schizophrenia: a resting state functional MRI study.
AB  - Avolition, a deficit in goal-directed behavior, is a key aspect of negative
      symptoms. It is highly prevalent in schizophrenia and is associated to poor
      functional outcome and to measures of real life motivation, indicating that
      central to the concept is the lack of interest and motivation. In this study we
      tested the hypothesis that avolition is related to altered connectivity within
      dopaminergic cortico-striatal circuits involved in motivation processes. Since
      dopamine input to these circuits derives mostly from the ventro-tegmental area
      (VTA), we investigated the relationships between the resting-state functional
      connectivity (RS-FC) of the VTA and avolition in twenty-six subjects with
      schizophrenia (SCZ), treated with second-generation antipsychotics only, compared
      to twenty-two healthy controls (HC). SCZ, in comparison to HC, showed
      significantly reduced RS-FC of the VTA with bilateral ventro-lateral prefrontal
      cortex (VLPFC), bilateral insular cortex (IC) and right (R) lateral occipital
      complex (LOC) and increased RS-FC of the VTA with bilateral dorso-lateral
      prefrontal cortex (DLPFC). Significant negative correlations were found between
      avolition and RS-FC of the VTA with the bilateral IC, R VLPFC and R LOC.
      According to our findings, avolition is linked to a disconnectivity of the VTA
      from several key cortical regions involved in the integration of value
      information with action selection. These findings are in line with translational
      animal models of "auto-activation apathy".

PMID- 29653744
TI  - Low expression of B-Cell-Associated protein 31 is associated with unfavorable
      prognosis in human colorectal cancer.
AB  - : Colorectal cancer (CRC) is one of the most common cancers worldwide. B cell
      associated protein 31 (BAP31) was shown to participate in the apoptosis, and to
      be an immunotherapy target and a, prognostic factor for cancer, but its role in
      CRC has not been elucidated. In this study, we examined the expression of BAP31
      in CRC to evaluate its prognostic values. We investigated the BAP31 expression
      level in 142 tissues (108 CRC and 17 paired human adjacent normal mucosa, and 17
      liver metastatic CRC tissues) from 108 patients, using tissue microarray-based
      immunohistochemistry. We further investigated the association between BAP31
      expression and overall survival (OS) and disease-free survival (DFS) in 77 CRC
      patients using Kaplan-Meier analysis. Univariate and multivariate Cox regression
      analyses were applied to evaluate the potential prognostic value of BAP31 in CRC
      patients. BAP31 expression level was significantly increased in CRC tissues (p =
      0.0014) and liver metastatic CRC tissues (p < 0.0001) compared with corresponding
      adjacent normal mucosa. BAP31 expression was also significantly increased in
      liver metastatic CRC tissues compared with corresponding primary CRC tissues (p =
      0.0116). Kaplan-Meier analyses showed that CRC patients with low BAP31 expression
      had significantly lower survival rate (p = 0.001) and lower disease-free survival
      rate (P = 0.009). Furthermore, multivariate Cox analysis showed that BAP31 was an
      independent prognostic factor for OS (hazard ratio = 0.410, 95% confidence
      interval = 0.195-0.862, p = 0.019). CONCLUSIONS: Our study demonstrated that
      BAP31 is a potential prognostic marker for CRC patients after surgery.

PMID- 29653745
TI  - Loss of PTEN in high grade advanced stage triple negative breast ductal cancers
      in African American women.
AB  - INTRODUCTION: PTEN is a tumor suppressor gene that inhibits cell proliferation by
      inhibiting the phosphoinositide 3-kinase (PI3 K) signaling pathway. The
      significance of PTEN mutations resulting in variable PTEN expression and their
      impact on prognosis of breast cancer is not well established. The objective of
      our study was to correlate the immunohistochemical expression of PTEN in the four
      major subtypes of breast carcinoma (Luminal A, Luminal B, HER2 positive, and
      Triple Negative) in a population of 202 African-American (AA) females with other
      clinicopathological factors. MATERIALS AND METHODS: Tissue microarrays (TMAs)
      were constructed from FFPE tumor blocks from primary ductal breast carcinomas in
      202 African-American females. Five micrometer sections were stained with a mouse
      monoclonal antibody against PTEN. The sections were evaluated for the intensity
      of cytoplasmic and nuclear reactivity. Bivariate analysis was done via chi2
      analysis and survivability data was calculated via the generation of Kaplan-Meier
      curves (SPSS v19). RESULTS: Loss of PTEN expression was associated with ER
      negative (p = 0.021), PR negative (p = 0.024) and triple negative (p = 0.0024)
      breast ductal cancers. It was marginally associated with distant metastasis (p =
      0.074). There was no association between PTEN loss and recurrence-free survival
      or overall survival. CONCLUSION: In our study, a statistically significant
      association between PTEN loss and the triple negative breast cancers (TNBC) was
      found in AA women. PTEN inhibits PI3 K resulting in decreased activation of
      downstream effector, mammalian target of rapamycin (mTOR). Loss of PTEN results
      in cell proliferation through activation of mTOR. Targeted therapy with mTOR
      inhibitors might be useful in the treatment of TNBC.

PMID- 29653746
TI  - SRT1720, a potential sensitizer for radiotherapy and cytotoxicity effects of NVB
      BEZ235 in metastatic breast cancer cells.
AB  - BACKGROUND: Chemo-radio therapy (CRT) resistance is a main barrier in treating
      the triple negative breast cancer (TNBC). The success of conventional treatment
      may be ameliorated by elevating the responsiveness of the cancer cells to CRT.
      NVP-BEZ235 as a PI3K/AKT/mTOR dual inhibitor has been shown promising results in
      treating breast cancer cells. However, potential radiation-sensitizing effect of
      NVP-BEZ235 in TNBC remained unclear. In addition, SIRT-1 activation state and
      environmental cytokine were identified as being responsible for cancer cells
      responses to CRT. Herein, we investigate the role of interleukin 6 (IL-6) as a
      tumor environmental cytokine and SIRT1 in the effectiveness of NVP-BEZ235 plus
      radiotherapy. MATERIAL AND METHODS: TNBC cells were pre-treated with/without IL-6
      and were exposed to single and combination of SRT1720 (SIRT1 activator)/EX-527
      (SIRT1 inhibitor) and/or NVP-BEZ235 and/or gamma radiation. The effect of our
      treatments on cellular growth was determined by MTT and the cellular death and
      CSCs percentage were determined by Flow cytometry. Senescence detection kit was
      used to assay the effect of our treatments on cellular senescence induction.
      RESULTS: Activation of SIRT1 via SRT1720 increased the efficacy of CRT in TNBC
      cells, especially when IL-6 exists in tumor microenvironment. Additionally, IL-6
      pre-treatment followed by exposure to SRT1720 and NVP-BEZ235 significantly
      increased sensitivity of the cancer stem cells to radiation (p < 0.05).
      CONCLUSION: Our result shows that combination of NVP-BEZ235 and SRT1720 may
      effectively improve late stage breast cancer cells therapeutics approach.
      Activation of SIRT1 and STAT3 in resistance breast cancer cells improves the in
      vitro therapeutic efficacy of CRT.

PMID- 29653747
TI  - MiR-449a suppresses cell migration and invasion by targeting PLAGL2 in breast
      cancer.
AB  - BACKGROUND: Breast cancer is one of the most common malignancies worldwide.
      However, the detailed molecular mechanisms underlying breast cancer metastasis
      are still incompletely clear. MicroRNAs (miRNAs) play a crucial role in cancer
      metastasis. In this study, we aimed to analyze the expression and function of miR
      449a in breast cancer. MATERIAL AND METHODS: A total of 15 human primary breast
      cancer tissues and adjacent non-cancerous tissues (10 pairs) were obtained. MiR
      449a was examined in tumor tissues and adjacent nontumorous tissues of breast
      cancer patients and cell lines by real-time PCR. The protein expression levels
      were analyzed by western blot and immunohistochemistry staining. Luciferase
      reporter assays was used to validate the target of miR-449a. The effect of miR
      449a on breast cancer cell migration and invasion were studied in vitro and in
      vivo. RESULTS: The expression levels of miR-449a were significantly decreased in
      breast cancer tissues and cell lines. Overexpression of miR-449a suppressed
      breast cancer cell proliferation, clone formation, migration, invasion and
      metastasis in vitro and in vivo. Pleomorphic adenoma gene like-2 (PLAGL2) was
      identified as a major target of miR-449a. Both overexpression of miR-449a
      inhibited the expression of PLAGL2 significantly and the knockdown of PLAGL2
      expression inhibited the breast cancer cell proliferation and metastasis.
      CONCLUSION: We demonstrate the miR-449a tumor suppressor role in breast cancer
      cell migration and invasion via targeting PLAGL2. These findings suggesting that
      miR-449a/PLAGL2 could serve as a therapeutic strategy for targeting breast
      cancer.

PMID- 29653748
TI  - Cervical Spine Fractures in Patients Undergoing Palliative Radiotherapy to the
      Cervical Spine: Implications for Practice.

PMID- 29653749
TI  - Women's Free-text Comments on their Quality of Life: An Exploratory Analysis from
      the UK Standardisation of Breast Radiotherapy (START) Trials for Early Breast
      Cancer.
AB  - AIMS: Exploratory analysis of patients' unsolicited written comments in the first
      2 years of the Standardisation of Breast Radiotherapy (START) trial quality of
      life study highlighted a potential effect of non-treatment-related problems on
      the ratings and interpretation of patient self-reported questionnaires. At 5
      years of follow-up all eligible subjects were invited to write comments to
      further explore these findings. MATERIALS AND METHODS: Using inductive
      qualitative methods informed by the exploratory analysis, comments were allocated
      to relevant themes. Key patient-reported outcome measures (PROMs), clinical and
      demographic factors were collated for patients who did and did not comment at 5
      years and comparisons between the groups explored. RESULTS: Of 2208 women
      completing baseline PROMs, 482 proffered comments from 0 to 24 months, forming
      nine distinct themes, including chronic conditions, life events and psychosocial
      concerns. At 5 years, 1041/1727 (60.3%) women contributed comments, of whom 500
      randomly selected participants formed the sample for analysis. Findings revealed
      comorbidity, impaired physical functioning and psychosocial problems as key
      themes, with prevalent adverse effects from local and systemic treatments. Eight
      new themes emerged at 5 years, including ageing, concerns about future cancer and
      positive aspects of care. Women commenting were better educated, slightly older
      and more likely to have had chemotherapy compared with non-commenters. They had
      significantly worse PROM scores for global health and key quality of life domains
      relevant to the difficulties they revealed. CONCLUSIONS: Difficult personal
      circumstances and other health concerns affected many women's PROM ratings at 5
      years of follow-up, in addition to ongoing cancer treatment effects. Greater
      attention to multiple sources of distress and adversity could facilitate
      personalised care and aid interpretation of PROMs.

PMID- 29653750
TI  - Induced pluripotent stem cells with NOTCH1 gene mutation show impaired
      differentiation into smooth muscle and endothelial cells: Implications for
      bicuspid aortic valve-related aortopathy.
AB  - OBJECTIVE: The NOTCH1 gene mutation has been identified in bicuspid aortic valve
      patients. We developed an in vitro model with human induced pluripotent stem
      cells (iPSCs) to evaluate the role of NOTCH1 in smooth muscle and endothelial
      cell (EC) differentiation. METHODS: The iPSCs were derived from a patient with a
      normal tricuspid aortic valve and aorta. The NOTCH1 gene was targeted in iPSCs
      with the Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR
      associated protein 9 nuclease (Cas9) system. The NOTCH1-/- (NOTCH1 homozygous
      knockout) and isogenic control iPSCs (wild type) were differentiated into neural
      crest stem cells (NCSCs) and into cardiovascular progenitor cells (CVPCs). The
      NCSCs were differentiated into smooth muscle cells (SMCs). The CVPCs were
      differentiated into ECs. The differentiations of SMCs and ECs were compared
      between NOTCH1-/- and wild type cells. RESULTS: The expression of NCSC markers
      (SRY-related HMG-box 10 and transcription factor AP-2 alpha) was significantly
      lower in NOTCH1-/-NCSCs than in wild type NCSCs. The SMCs derived from NOTCH1-/-
      NCSCs showed immature morphology with smaller size and decreased expression of
      all SMC-specific contractile proteins. In NOTCH1-/-CVPCs, the expression of ISL1,
      NKX2.5, and MYOCD was significantly lower than that in isogenic control CVPCs,
      indicating impaired differentiation from iPSCs to CVPCs. The NOTCH1-/-ECs derived
      from CVPCs showed significantly lower expression of cluster of differentiation
      105 and cluster of differentiation 31 mRNA and protein, indicating a defective
      differentiation process. CONCLUSIONS: NOTCH1 is critical in SMC and EC
      differentiation of iPSCs through NCSCs and CVPCs, respectively. NOTCH1 gene
      mutations might potentially contribute to the development of thoracic aortic
      aneurysms by affecting SMC differentiation in some patients with bicuspid aortic
      valve.

PMID- 29653751
TI  - Esophageal injury: Tissue is always the issue.

PMID- 29653752
TI  - Frailty as a risk predictor in cardiac surgery: Beyond the eyeball test.

PMID- 29653753
TI  - Goldilocks meets heparin dosing-enough but not too much.

PMID- 29653754
TI  - Finding a needle in a haystack of needles: The difficulty of defining a
      consistently meaningful cytokine signature.

PMID- 29653755
TI  - Prophylactic tricuspid repair: The battle is lost, but the war is not over.

PMID- 29653756
TI  - The London sign (patterned bruising of blunt abdominal trauma).
AB  - Patterned bruising of abdominal wall in blunt trauma is called London sign. It
      indicates that the impacting force is sharp and severe enough to cause visceral
      injury. Despite its practical significance this sign is seldom described in
      textbooks and there are no journal articles about it. This communication is
      intended to draw the attention of pediatric surgeons to this useful clinical
      sign.

PMID- 29653757
TI  - No-fistula vs. fistula type anorectal malformation: Outcome comparative study.
AB  - INTRODUCTION: Anorectal malformation (ARM) is a congenital defect that exists in
      varying presentations and no-fistula type (NFT) ARM is a rare high-type category.
      We aim to report our experience with management of this anomaly and its outcome,
      compared to the more common fistula-type (FT) ARM. METHODS: A retrospective
      review of medical records of patients diagnosed with high ARM and 3years and
      older, for the period between September 2000 and January 2015 was conducted.
      Demographic, anatomic, and outcome data were obtained for each group and
      compared. Quality of life data were collected using the Krickenbeck
      classification and assessed as documented at clinic visits as well as phone
      interviews. RESULTS: There were 100 patients managed for ARM during that period
      and were 3years or older. Sixteen of them were NFT (16%). For comparison purposes
      each NFT patient was matched with 3 FT patients. We have analyzed data on 44
      patients with FT (44 males), and 16 with NFT (12 males and 4 females). The
      occurrence of Down syndrome in NFT patients was 56.2% compared to 0% in the FT
      patients (p=<0.0001). Quality of Life data showed no significant differences
      between the two groups with p-values of 0.39, 1.0, and 1.0 for Voluntary Bowel
      Movement, Soiling, and Constipation respectively. CONCLUSION: NFT ARM represents
      a significant number at our population (16%). There is a strong association
      between NFT ARM and Down syndrome. NFT ARM has similar outcomes compared to the
      FT ARM. TYPE OF STUDY: Clinical research paper. LEVEL OF EVIDENCE: Level III.

PMID- 29653758
TI  - The "perfect" reader study.
AB  - A reader study, i.e. a diagnostic accuracy study aiming to assess clinical
      performance of one technology versus another, on the basis of image
      interpretation by a group of human readers, requires an accurate design, with the
      precise definition of each element concurring to the study itself. In this paper,
      the main issues to take into consideration when designing reader studies are
      described, and the characteristics of a number of indices of diagnostic accuracy
      are summarized. Special care is given to the description of the multiple sources
      of bias, which should be controlled in order to assure study soundness and allow
      consistent conclusions. Although a "perfect" reader study does not exist, because
      bias cannot be completely eliminated, a good study would be designed to minimize
      the bias effects, and possible unavoidable bias should be described in study
      reporting and used to provide a correct interpretation of results.

PMID- 29653759
TI  - Drinking water treatment sludge as an effective additive for biogas production
      from food waste; kinetic evaluation and biomethane potential test.
AB  - The effect of drinking water treatment sludge (DWTS) as a mixture additive, on
      biogas and methane production from food waste was studied. Mesophilic anaerobic
      digestion of food waste with 5 concentrations of DWTS (0, 2, 6, 12, and 18 ppm)
      was carried out. It was found that DWTS can significantly enhance biogas and
      methane yield. The highest biogas (671 Nml/g VS) as well as methane yield (522
      Nml/g VS) was observed when 6 mg/kg DWTS was added. This is equal to 65 and 58
      percent increase in comparison with the control digester. The calculated lag time
      for methane was found to be in between 3.3 and 4.7 days. The DWTS also reduced
      the lag phase and retention time. The biogas experimental data was fitted with
      the modified Gompertz and the first-order kinetic models with R2 higher than
      0.994 and 0.949, respectively. The ratio of the experimental biogas production to
      the theoretical biogas production (E) for control sample was 0.53 while for other
      samples containing additive were higher than 0.78.

PMID- 29653761
TI  - Lipoprotein(a) levels are doubled in left-handed patients with diabetes.

PMID- 29653760
TI  - A Novel Amino Lipid Series for mRNA Delivery: Improved Endosomal Escape and
      Sustained Pharmacology and Safety in Non-human Primates.
AB  - The success of mRNA-based therapies depends on the availability of a safe and
      efficient delivery vehicle. Lipid nanoparticles have been identified as a viable
      option. However, there are concerns whether an acceptable tolerability profile
      for chronic dosing can be achieved. The efficiency and tolerability of lipid
      nanoparticles has been attributed to the amino lipid. Therefore, we developed a
      new series of amino lipids that address this concern. Clear structure-activity
      relationships were developed that resulted in a new amino lipid that affords
      efficient mRNA delivery in rodent and primate models with optimal
      pharmacokinetics. A 1-month toxicology evaluation in rat and non-human primate
      demonstrated no adverse events with the new lipid nanoparticle system.
      Mechanistic studies demonstrate that the improved efficiency can be attributed to
      increased endosomal escape. This effort has resulted in the first example of the
      ability to safely repeat dose mRNA-containing lipid nanoparticles in non-human
      primate at therapeutically relevant levels.

PMID- 29653762
TI  - Concerns regarding 'off-target' activity of genome editing endonucleases.
AB  - Genome editing (GE) tools ensure targeted mutagenesis and sequence-specific
      modification in plants using a wide resource of customized endonucleases; namely,
      zinc-finger nucleases (ZFNs), and transcription activator-like effector nucleases
      (TALENs), and the CRISPR (clustered regularly interspaced short palindromic
      repeats)/Cas (CRISPR-associated protein) system. Among these, in recent times
      CRISPR/Cas9 has been widely used in functional genomics and plant genetic
      modification. A significant concern in the application of GE tools is the
      occurrence of 'off-target' activity and induced mutations, which may impede
      functional analysis and gene activity studies. Moreover, the 'off-target'
      activity results in either not reported or unknown, difficult to detect, produce
      non-quantifiable cellular signaling and physiological effects. In the past few
      years, several experimental methods have been developed to identify undesired
      mutations and to curtail 'off-target' cleavage. Improvement in target specificity
      and minimizing 'off-target' activity will offer better applications of GE
      technology in plant biology and crop improvement.

PMID- 29653763
TI  - The significance of levels of organization for scientific research: A heuristic
      approach.
AB  - The concept of 'levels of organization' has come under fire recently as being
      useless for scientific and philosophical purposes. In this paper, we show that
      'levels' is actually a remarkably resilient and constructive conceptual tool that
      can be, and in fact is, used for a variety of purposes. To this effect, we
      articulate an account of the importance of the levels concept seen in light of
      its status as a major organizing concept of biology. We argue that the usefulness
      of 'levels' is best seen in the heuristic contributions the concept makes to
      treating and structuring scientific problems. We illustrate this with two
      examples from biological research.

PMID- 29653765
TI  - Necessity for additional sensitivity analysis and the clinical implications of
      risk identification with nonventilator hospital-acquired pneumonia.

PMID- 29653764
TI  - Radiation dose reduction by adjusting bolus tracking parameters in a 320-detector
      row scanner.
AB  - BACKGROUND: The importance of bolus tracking (BT) regarding total effective
      radiation dose (ERD) in the era of advanced coronary computed tomography
      angiography (CTA) has been ignored. We aimed to investigate whether adjusting BT
      parameters reduces ERD. METHODS: Adults consecutively referred to CTA (n = 289)
      in a 320 detector-row scanner were distributed into four BT protocols according
      to delay time and time between intermittent scans, as follows: A (n = 70, delay
      10s, intermittent scans 1s); B (n = 79, delay 10s, intermittent scans 2s); C (n =
      68, delay 15s, intermittent scans 1s); and D (n = 72, delay 15s, intermittent
      scans 2s). Image quality was assessed. RESULTS: The overall ERD in BT and AP were
      0.32 +/- 0.14 mSv and 6.06 +/- 0.66 mSv, respectively. ERD in BT was different
      among protocols (A:0.44 +/- 0.14 mSv; B:0.32 +/- 0.10 mSv; C:0.28 +/- 0.14 mSv;
      D:0.23 +/- 0.09 mSv; p < 0.001), with no loss in image quality. Adjusted for
      potential confounders (heart rate, tube current and acquisition window), protocol
      D provided the highest reduction in total ERD (beta = -0.33, p = 0.004).
      CONCLUSION: Delaying initiation of BT images (and acquiring them less frequently)
      reduces radiation dose and does not impair image quality.

PMID- 29653766
TI  - [Correlation between pneumoperitoneum and surgical findings and morbidity and
      mortality in newborns with necrotising enterocolitis].
AB  - INTRODUCTION: Surgical intervention in necrotising enterocolitis (NEC) is correct
      when there is intestinal gangrene. This is evident when gangrene produces
      perforation and pneumoperitoneum, with this being the only universally accepted
      radiological indication for the surgical intervention of NEC. OBJECTIVE: To
      perform an analysis on patients with surgically managed NEC, including
      determining how the decision to intervene is reached, the outcomes, and if
      patients with perforation had a pneumoperitoneum. METHODS: Retrospective review
      of neonates with surgical NEC over a period of 10years (2006-2015). An analysis
      was made of pre-surgical x-ray findings, which were compared with surgical ones,
      in addition to the morbidity and mortality, depending on the presence (N+) or
      absence (N-) of pneumoperitoneum. An evaluation was also made of the
      interobserver concordance with a paediatric radiologist blinded to the clinical
      reason using the kappa agreement index. RESULTS: A total of 53 neonates were
      included in the study. Surgical treatment was indicated after observing
      pneumoperitoneum in 36%. In the remaining neonates, the surgical decision was
      made after noting a clinical and metabolic deterioration with classical x-ray
      findings. Intestinal perforation was observed in 39% of the N- neonates. There
      were no statistical differences between either group on analysing the excised
      intestinal length, days of intubation, starting of enteral nutrition, and the
      mortality rate. Comparisons in terms of duration of symptoms and total hospital
      stay were statistically significant (7 vs. 2 days, P=.008; 127 vs. 79 days,
      P=.003, respectively), with both being more favourable in the N+ group. These
      differences remained when the groups were adjusted by birthweight. CONCLUSIONS:
      Surgical indication has to be done on an ensemble of clinical and radiological
      evidence, as 39% of the neonates in the N- groups were perforated. In our study,
      the presence of a pneumoperitoneum did not correlate with a worse prognosis.

PMID- 29653767
TI  - Response from Dr. Long et al.

PMID- 29653768
TI  - Clinical innovation in stroke: getting the simple things right.

PMID- 29653770
TI  - A Comparative Study of Carvedilol Versus Metoprolol Initiation and 1-Year
      Mortality Among Individuals Receiving Maintenance Hemodialysis.
AB  - BACKGROUND: Carvedilol and metoprolol are the beta-blockers most commonly
      prescribed to US hemodialysis patients, accounting for ~80% of beta-blocker
      prescriptions. Despite well-established pharmacologic and pharmacokinetic
      differences between the 2 medications, little is known about their relative
      safety and efficacy in the hemodialysis population. STUDY DESIGN: A retrospective
      cohort study using a new-user design. SETTING & PARTICIPANTS: Medicare-enrolled
      hemodialysis patients treated at a large US dialysis organization who initiated
      carvedilol or metoprolol therapy from January 1, 2007, through December 30, 2012.
      PREDICTOR: Carvedilol versus metoprolol initiation. OUTCOMES: All-cause
      mortality, cardiovascular mortality, and intradialytic hypotension (systolic
      blood pressure decrease >= 20mmHg during hemodialysis plus intradialytic saline
      solution administration) during a 1-year follow-up period. MEASUREMENTS: Survival
      models were used to estimate HRs and 95% CIs in mortality analyses. Poisson
      regression was used to estimate incidence rate ratios (IRRs) and 95% CIs in
      intradialytic hypotension analyses. Inverse probability of treatment weighting
      was used to adjust for several demographic, clinical, laboratory, and dialysis
      treatment covariates in all analyses. RESULTS: 27,064 individuals receiving
      maintenance hemodialysis were included: 9,558 (35.3%) carvedilol initiators and
      17,506 (64.7%) metoprolol initiators. Carvedilol (vs metoprolol) initiation was
      associated with greater all-cause (adjusted HR, 1.08; 95% CI, 1.02-1.16) and
      cardiovascular mortality (adjusted HR, 1.18; 95% CI, 1.08-1.29). In subgroup
      analyses, similar associations were observed among patients with hypertension,
      atrial fibrillation, heart failure, and a recent myocardial infarction, the main
      cardiovascular indications for beta-blocker therapy. During follow-up, carvedilol
      (vs metoprolol) initiators had a higher rate of intradialytic hypotension
      (adjusted IRR, 1.10; 95% CI, 1.09-1.11). LIMITATIONS: Residual confounding may
      exist. CONCLUSIONS: Relative to metoprolol initiation, carvedilol initiation was
      associated with higher 1-year all-cause and cardiovascular mortality. One
      potential mechanism for these findings may be the increased occurrence of
      intradialytic hypotension after carvedilol (vs metoprolol) initiation.

PMID- 29653771
TI  - Ensuring safe and optimal medication use in older community residents:
      Collaboration between a nurse and a pharmacist.
AB  - The purpose of this retrospective review is to describe 1) a nurse-pharmacist
      collaboration within a home based nurse-occupational therapist-handyman program
      called CAPABLE and 2) potential medication problems and 3) information
      communicated to participants and prescribers about those problems. A chart review
      was performed for each participant that one CAPABLE nurse referred to the
      pharmacists. We identified recommendations provided by pharmacists, synthesized
      common questions posed to the pharmacists' and developed exemplar cases of
      participant encounters. Fifty-nine participants were reviewed. The median number
      of total medications was 11 (IQR 9-14.5). Participants were most commonly taking
      antihypertensives (93%), statins (66%), and supplements/vitamins (61%).
      Pharmacists provided 83 unique recommendations for the 59 participants. The
      recommendations from the pharmacist were communicated for 49 of the 59
      participants (83%), by the nurse. The nurse-pharmacist collaboration identified
      medication-related problems and solutions aimed at improving the quality of life
      for home-dwelling seniors with functional limitations.

PMID- 29653772
TI  - Correlates and influences of taking an afternoon nap on nocturnal sleep in
      Chinese elderly: A qualitative study.
AB  - Taking afternoon naps is common among elderly people, but the information about
      napping from qualitative viewpoints is limited. This study aimed to describe
      napping experience from the perspectives of Chinese elderly, specifically on nap
      taking correlates and its influences on nocturnal sleep. Data were gathered via
      individual in-depth interviews with 50 Chinese elderly in Taiwan. The majority of
      the nappers napped for 1-2 hours between 12 PM and 1 PM. Nap promoting factors
      included "belief in afternoon nap taking benefits," "nothing to do," "low energy
      level," "compensation -for disturbed sleep" and "extreme weather." Nap taking (>1
      hr.) was found to be associated with delay of the onset of sleep, reduction of
      sleep duration, and light sleep. Short afternoon napping (<1 hour) is recommended
      for the elderly. Future research should determine the direction of the causative
      association between afternoon nap-taking and nocturnal sleep.

PMID- 29653769
TI  - Estimating Time to ESRD in Children With CKD.
AB  - RATIONALE & OBJECTIVE: The KDIGO (Kidney Disease: Improving Global Outcomes)
      guideline for chronic kidney disease (CKD) presented an international
      classification system that ranks patients' risk for CKD progression. Few data for
      children informed guideline development. STUDY DESIGN: Observational cohort
      study. SETTINGS & PARTICIPANTS: Children aged 1 to 18 years enrolled in the North
      American Chronic Kidney Disease in Children (CKiD) cohort study and the European
      Effect of Strict Blood Pressure Control and ACE Inhibition on the Progression of
      CRF in Pediatric Patients (ESCAPE) trial. PREDICTOR: Level of estimated
      glomerular filtration rate (eGFR) and proteinuria (urine protein-creatinine ratio
      [UPCR]) at study entry. OUTCOME: A composite event of renal replacement therapy,
      50% reduction in eGFR, or eGFR<15mL/min/1.73m2. eGFR was estimated using the CKiD
      derived "bedside" equation. ANALYTICAL APPROACH: Accelerated failure time models
      of the composite outcome using a conventional generalized gamma distribution.
      Likelihood ratio statistics of nested models were used to amalgamate levels of
      similar risk. RESULTS: Among 1,232 children, median age was 12 (IQR, 8-15) years,
      median eGFR was 47 (IQR, 33-62) mL/min/1.73m2, 60% were males, and 13% had
      UPCRs>2.0mg/mg at study entry. 6 ordered stages with varying combinations of eGFR
      categories (60-89, 45-59, 30-44, and 15-29mL/min/1.73m2) and UPCR categories
      (<0.5, 0.5-2.0, and >2.0mg/mg) described the risk continuum. Median times to
      event ranged from longer than 10 years for eGFRs of 45 to 90mL/min/1.73m2 and
      UPCRs<0.5mg/mg to 0.8 years for eGFRs of 15 to 30mL/min/1.73m2 and UPCRs>2mg/mg.
      Children with glomerular disease were estimated to have a 43% shorter time to
      event than children with nonglomerular disease. Cross-validation demonstrated
      risk patterns that were consistent across the 10 subsample validation models.
      LIMITATIONS: Observational study, used cross-validation rather than external
      validation. CONCLUSIONS: CKD staged by level of eGFR and proteinuria
      characterizes the timeline of progression and can guide management strategies in
      children.

PMID- 29653773
TI  - Can Biannual Ultrasound Surveillance Detect Smaller Second Cancers or Detect
      Cancers Earlier in Patients with Breast Cancer History?
AB  - The aim of the work described here was to evaluate whether surveillance with
      biannual ultrasound (US) plus annual mammography (biannual group) for women with
      a history of breast cancer surgery results in earlier detection or in the
      detection of smaller second cancers than annual US plus mammography (annual
      group). Additionally, we compared the prevalence of distant metastases or
      palpable second cancers between the biannual and annual groups. The institutional
      review board of our institution approved this retrospective study, and patient
      consent was waived. Between January 2011 and December 2012, we retrospectively
      reviewed the clinical and imaging follow-up of 3023 patients with mammographic
      and US surveillance after breast cancer surgery to assess second cancers detected
      by local surveillance (locoregional recurrence, contralateral breast cancer or
      distant metastasis). The biannual and annual groups were divided with respect to
      the mean surveillance interval and compared with respect to clinicopathologic
      findings. Multivariable logistic regression with propensity score methods was
      used to examine the effect of the type of surveillance on outcomes. As for the
      size of the second cancer, no difference was seen between the biannual and annual
      groups (12.8 +/- 6.6 mm vs. 14.1 +/- 7.1 mm, p = 0.461); neither was there a
      significant difference between the groups in the presence of symptoms at the time
      of diagnosis of the second cancer (17.0% [8/47] vs. 10% [2/20], p = 0.711).
      Regardless of detection by local surveillance, the prevalence of distant
      metastases did not differ between the two groups (1.1% [27/2370] vs. 1.0%
      [7/653], p = 0.88) on univariate or multivariate analysis. The results of our
      retrospective study indicate that second cancers detected by biannual US
      surveillance in patients with a history of breast cancer surgery are not smaller
      and do not occur earlier than those detected by annual US surveillance. However,
      a randomized controlled study is required to verify these results before they can
      be generalized to clinical practice.

PMID- 29653774
TI  - Pre-Operative Planning Using Real-Time Virtual Sonography, an MRI/Ultrasound
      Image Fusion Technique, for Breast-Conserving Surgery in Patients with Non-Mass
      Enhancement on Breast MRI: A Preliminary Study.
AB  - The purpose of this retrospective study was to evaluate the effect of pre
      operative planning using real-time virtual sonography (RVS), a magnetic resonance
      imaging (MRI)/ultrasound (US) image fusion technique on breast-conserving surgery
      (BCS) in patients with non-mass enhancement (NME) on breast MRI. Between 2011 and
      2015, we enrolled 12 consecutive patients who had lesions with NME that exceeded
      the US hypo-echoic area, in which it was particularly difficult to evaluate the
      tumor margin. During pre-operative planning before breast-conserving surgery, RVS
      was used to delineate the enhancing area on the breast surface after additional
      supine breast MRI was performed. We analyzed both the surgical margin positivity
      rate and the re-operation rate. All NME lesions corresponded to the index cancer.
      In all patients, the diameter of the NME lesion was greater than that of the hypo
      echoic lesion. The median diameters of the NME and hypo-echoic lesions were 24 mm
      (range: 12-39 mm) and 8.0 mm (range: 4.9-18 mm), respectively (p = 0.0002). After
      RVS-derived skin marking was performed on the surface of the affected breast,
      lumpectomy and quadrantectomy were conducted in 7 and 5 patients, respectively.
      The surgical margins were negative in 10 (83%) patients. Two patients with
      positive margins were found to have ductal carcinoma in situ in 1 duct each, 2.4
      and 3.2 mm from the resection margin, respectively. None of the patients required
      additional resection. Although further prospective studies are required, the
      findings of our preliminary study suggest that it is very well possible that the
      use of RVS-derived skin marking during pre-operative planning for BCS in patients
      with NME would have resulted in surgical outcomes similar to or better than those
      obtained without the use of such marking.

PMID- 29653775
TI  - Evidence and Indications for Percutaneous Closure of the Left Atrial Appendage.

PMID- 29653776
TI  - Reversibility of Alcohol Dilated Cardiomyopathy.

PMID- 29653777
TI  - New-onset or Pre-existing Atrial Fibrillation in Acute Coronary Syndromes: Two
      Distinct Phenomena With a Similar Prognosis.
AB  - INTRODUCTION AND OBJECTIVES: The management and risk stratification of patients
      with atrial fibrillation (AF) and acute coronary syndromes constitute a
      challenge. We aimed to evaluate the prognostic impact of AF whether present at
      admission or occurring during hospitalization for acute coronary syndromes, as
      well as trends in treatments and outcome. METHODS: Data derived from 35 958
      patients enrolled between 2004 and 2015 in the AMIS Plus registry were
      retrospectively analyzed. RESULTS: Pre-existing AF (pre-AF) was present in 1644
      (4.7%) while new-onset AF (new-AF) was evident in 309 (0.8%). Presentation with
      ST-segment elevation myocardial infarction and need for hemodynamic support was
      frequent in patients with AF, especially in those with new onset of the
      arrhythmia. A change of the medical and interventional approaches was observed
      with a progressive increase in oral anticoagulation prescription and referral for
      angiography and percutaneous coronary interventions in pre-AF patients. Despite
      different baseline risk profile and clinical presentations, both AF groups showed
      high in-hospital and 1-year mortality (in-hospital new-AF vs pre-AF [OR, 0.79;
      95%CI, 0.53-1.17; P = .246]; 1-year mortality new-AF vs pre-AF [OR, 0.72; 95%CI,
      0.31-1.67; P = .448]) Pre-AF but not new-AF independently predicted in-hospital
      mortality. While mortality declined over the study period for patients with pre
      AF, it remained stable among new-AF patients. CONCLUSIONS: While pre-AF is
      independently associated with in-hospital mortality, new-AF may reflect a worse
      hemodynamic impact of the acute coronary syndromes, with the latter ultimately
      driving the prognosis.

PMID- 29653778
TI  - Immobilization of a phosphonium ionic liquid on a silica monolith for hydrophilic
      interaction chromatography.
AB  - A methodology for preparing phosphonium-based ionic liquid modified silica-based
      monolithic capillary columns is presented. The silica monolithic columns with
      dimensions of 150 * 0.1 mm were modified by a phosphonium-based ionic liquid
      (trioctyl(3/4-vinylbenzyl)phosphonium chloride) via 3-(trimethoxysilyl)propyl
      methacrylate. The prepared columns were evaluated under hydrophilic interaction
      liquid chromatography separation conditions, employing a sample mixture
      containing purine and pyrimidine bases and nucleosides. Detection was made by UV.
      The high efficiency of the original silica monolith was preserved even after
      modification, and it reached values in the range of 98,000-174,000 theoretical
      plates/m. The effects of the concentration of acetonitrile in the mobile phase,
      the presence of additives in the mobile phase, such as, acetic acid or ammonium
      acetate, and the pH of the mobile phase on the separation of some selected
      analytes were investigated. The prepared columns showed different separation
      selectivity compared to silica, phenyl and sulfobetaine stationary phases.

PMID- 29653779
TI  - Melamine sponge decorated with copper sheets as a material with outstanding
      properties for microextraction of sulfonamides prior to their determination by
      high-performance liquid chromatography.
AB  - In this study, the modification/loading of melamine sponge with metallic copper
      sheets (CuMeS) is discussed. The CuMeS is prepared in a fast, singe-step
      procedure, where concurrent production of copper oxides is avoided. The as
      prepared CuMeS is utilized to develop a sensitive and selective sample
      preparation procedure to extract sulfonamides (SAs) from milk and water samples.
      The surface of the resulting CuMeS, after drying is rendered hydrophobic enabling
      hydrophobic interactions. To the best of our knowledge, this is the first time
      that the benefits of the high affinity of copper for SAs are reaped for
      analytical purposes. Due to the high selectivity, the proposed CuMeS-based
      procedure acts both as extraction and clean-up for the quantitative determination
      of SAs. The analytical method developed herein, which is based on the extractive
      potential of CuMeS, has the merits of wide linearity (including concentrations
      above and below the maximum residue limit of SAs), low limits of quantification
      (0.025-0.057MUgL-1 for lake water and 0.23-1.05MUgL-1 for milk samples), high
      enrichment factors and highly satisfactory recoveries and repeatability. The
      analytical method is validated according to the Commission Decision 657/2002/EC.
      Owing to the low cost of CuMeS and the straightforward procedure followed the
      proposed method can be applied to routine analysis of SAs.

PMID- 29653780
TI  - Implementation of multicriteria decision analysis in design of experiment for
      dispersive liquid-liquid microextraction optimization for chlorophenols
      determination.
AB  - A novel and efficient approach to optimization of extraction step prior the
      chromatographic determination of nine chlorinated phenols is described. It is
      based on the combination of design of experiments and multicriteria decision
      analysis. Such an approach is used to optimize dispersive liquid-liquid
      microextraction procedure for the determination of 9 chlorophenols in water
      samples. Three parameters are optimized - sample volume, volume of disperser
      solvent and extraction solvent. Combination of the technique for order of
      preference by similarity to ideal solution with central composite design allows
      to perform multi-analyte procedure optimization. It gives information about the
      efficiency of the system for every experimental plan point in terms of closeness
      to ideal solution. The optimal conditions for extraction of chlorophenols are 76
      MUL of extraction solvent, 0.6 mL of dispersive solvent and 6.7 mL of water
      sample. The presented approach has the potential to be applied in variety of
      optimization systems.

PMID- 29653782
TI  - Epicuticular wax on leaf cuticles does not establish the transpiration barrier,
      which is essentially formed by intracuticular wax.
AB  - It is well established that waxes built up the barrier properties of cuticles,
      since their extraction in organic solvent e.g. chloroform increases diffusion of
      water and organic compounds by 1-2 orders of magnitude. Leaf surface waxes can be
      divided in epicuticular (on the surface of the cuticular membrane) and
      intracuticular (embedded in the cutin polymer) waxes. Until today there are only
      limited investigations dealing with the question to what extent epi- or
      intracuticular waxes contribute to the formation of the transpiration barrier.
      For Prunus laurocerasus previous studies have shown that epicuticular waxes do
      not contribute to the formation of the transpiration barrier. This approach
      successfully established for P. laurocerasus was applied to further species in
      order to check whether this finding also applies to a broader spectrum of
      species. Epicuticular wax was mechanically removed using collodion from the
      surface of either isolated cuticular membranes or intact leaf discs of ten
      further plant species differing in total wax amounts, wax compositions and
      transport properties. Scanning electron microscopy, which was performed to
      independently verify the successful removal of the surface waxes, indicated that
      two consecutive treatments with collodion were sufficient for a complete removal
      of epicuticular wax. The treated surfaces appeared smooth after removal. The
      total wax amounts removed with the two collodion treatments and the residual
      amount of waxes after collodion treatment were quantified by gas chromatography
      and mass spectrometry. This showed that epicuticular waxes essentially consisted
      of long-chain aliphatic molecules (e.g. alkanes, primary alcohols, fatty acids),
      whereas intracuticular wax was composed of both, triterpenoids and long-chain
      aliphatic molecules. Cuticular transpiration using combined replicates was
      measured before and after removal of surface wax. Results clearly indicated that
      two consecutive collodion treatments, or the corresponding solvent treatments
      (diethyl ether:ethanol) serving as control, did not increase cuticular
      transpiration of the ten further leaf species investigated. Our results lead to
      the conclusion that epicuticular wax does not contribute to the formation of the
      transpiration barrier of leaves.

PMID- 29653781
TI  - Neoadjuvant systemic treatment for breast cancer in Italy: The Italian Society of
      Surgical Oncology (SICO) Breast Oncoteam survey.
AB  - The Italian Society of Surgical Oncology (SICO) Breast Oncoteam developed a
      survey to explore the state of the art of neoadjuvant treatment for breast cancer
      in Italy, specifically focusing on cases treated during the two-year period 2014
      2015. A questionnaire was sent to Italian Breast Units with a minimum of 150 new
      breast cancer cases treated/year according to the Senonetwork directory and to
      the SICO Breast Oncoteam Breast Unit network. A total of 23/107 Breast Units
      submitted the survey, reporting a total amount of 20156 cases of breast carcinoma
      (17241 invasive, 2915 in situ) treated in the biennium, corresponding
      approximately to 20% of newly diagnosed breast cancers in Italy. In the United
      States, medical treatment before surgery for breast cancer is indicated in about
      22.7% of newly diagnosed cases according to the National Cancer Database, while a
      German study reported approximately 20% of cases treated with neoadjuvant
      therapy. In our survey, a total of 1673/17241 cases (9.7%) were treated with
      neoadjuvant therapy, ranging from 2.9% to 23.6% according to different centres,
      showing heterogeneity in neoadjuvant treatment indications, even in
      multidisciplinary breast units. Better resources should be engaged to achieve a
      standardised quality indicator for neoadjuvant treatment, and this indicator
      could be included among the European Society of Breast Cancer Specialists
      (EUSOMA) quality indicators. In the near future, we plan to develop a second
      survey to better test improvements in the employment of neoadjuvant therapy after
      the expiry of the 2016 European Parliament deadline and after the 2017 St. Gallen
      Conference recommendations.

PMID- 29653783
TI  - In Reply to Drs Sikri and Bhattachar.

PMID- 29653785
TI  - Icatibant for the treatment of orolingual angioedema following the administration
      of tissue plasminogen activator.

PMID- 29653784
TI  - Adenoid cystic carcinoma of head and neck: A retrospective clinical analysis of a
      single institution.

PMID- 29653786
TI  - Compression with a pocket-sized ultrasound device to diagnose proximal deep vein
      thrombosis.
AB  - INTRODUCTION: Compression ultrasonography (CUS) is a validated technique for the
      diagnosis of deep venous thrombosis (DVT), but has never been studied with pocket
      sized ultrasound device (PUD). The main objective of this study was to assess the
      diagnostic performance of CUS made by emergency physicians (EPs) using a PUD.
      MATERIALS: This was a prospective, diagnostic test assessment, single-center
      study. Patients underwent VCU performed by a trained EP with PUD (CUS-PUD) for
      searching proximal DVT (PDVT) and were then seen by an expert vascular physician
      who blindly performed a duplex venous ultrasound, which was the criterion
      standard. CUS-PUD's diagnostic performance was evaluated by sensitivity (Se),
      specificity (Sp), and positive and negative predictive values (PPV and NPV).
      RESULTS: The sample included 57 patients of whom 56 were analyzed. Eleven (20%)
      PDVT were diagnosed with CUS-PUD: 7 (64%) femoral and 4 (36%) popliteal. The CUS
      PUD's Se was 100% [72%; 100%], Sp 100% [92%; 100%]. The PPV was 100% [74%; 100%],
      and the NPV was 100% [90%; 100%]. CONCLUSION: CUS-PUD performed with a pocket
      sized ultrasound appears to be feasible in emergency practice for the diagnosis
      of proximal DVT. A study with a larger sample size will have to describe the
      accuracy.

PMID- 29653787
TI  - The early chain of care in bacteraemia patients: Early suspicion, treatment and
      survival in prehospital emergency care.
AB  - INTRODUCTION: Bacteraemia is a first stage for patients risking conditions such
      as septic shock. The primary aim of this study is to describe factors in the
      early chain of care in bacteraemia, factors associated with increased chance of
      survival during the subsequent 28days after admission to hospital. Furthermore,
      the long-term outcome was assessed. METHODS: This study has a quantitative design
      based on data from Emergency Medical Services (EMS) and hospital records.
      RESULTS: In all, 961 patients were included in the study. Of these patients,
      13.5% died during the first 28days. The EMS was more frequently used by non
      survivors. Among patients who used the EMS, the suspicion of sepsis already on
      scene was more frequent in survivors. Similarly, EMS personnel noted the ESS code
      "fever, infection" more frequently for survivors upon arriving on scene. The
      delay time from call to the EMS and admission to hospital until start of
      antibiotics was similar in survivors and non-survivors. The five-year mortality
      rate was 50.8%. Five-year mortality was 62.6% among those who used the EMS and
      29.5% among those who did not (p<0.0001). CONCLUSION: This study shows that among
      patients with bacteraemia who used the EMS, an early suspicion of sepsis or
      fever/infection was associated with improved early survival whereas the delay
      time from call to the EMS and admission to hospital until start of treatment with
      antibiotics was not. 50.8% of all patients were dead after five years.

PMID- 29653789
TI  - Comparative analysis of incapacitated versus forcible sexual assault in a
      community-based population.

PMID- 29653788
TI  - Shift in U.S. payer responsibility for the acute care of violent injuries after
      the Affordable Care Act: Implications for prevention.
AB  - BACKGROUND: Investment in violence prevention programs is hampered by lack of
      clearly identifiable stakeholders with a financial stake in prevention. We
      determined the total annual charges for the acute care of injuries from
      interpersonal violence and the shift in financial responsibility for these
      charges after the Medicaid expansion from the Affordable Care Act in 2014.
      METHODS: We analyzed all emergency department (ED) visits from 2009 to 2014 with
      diagnosis codes for violent injury in the Nationwide Emergency Department Sample
      (NEDS). We used sample weights to estimate total charges with adjusted
      generalized linear models to estimate charges for the 15% of ED visits with
      missing charge data. We then calculated the share attributable by payer and
      determined the difference in proportion by payer from 2013 to 2014. RESULTS:
      Between 2009 and 2013, the uninsured accounted for 28.2-31.3% of annual charges
      for the acute care of violent injury, while Medicaid was responsible for a
      similar amount (29.0-31.0%). In 2014, there were $10.7 billion in total charges
      for violent injury. Medicaid assumed the greatest share, 39.8% (95% CI: 38.0
      41.5%, $3.5-5.1 billion), while the uninsured accounted for 23.6% (95% CI: 22.2
      24.9%, $2.0-3.0 billion), and Medicare accounted for 7.8% (95% CI: 7.7-8.0%, $0.7
      1.0 billion). CONCLUSION: After Medicaid expansion, taxpayers are now accountable
      for nearly half of the $10.7 billion in annual charges for the acute care of
      violent injury in the U.S. These findings highlight the benefit to state Medicaid
      programs of preventing interpersonal violence.

PMID- 29653790
TI  - Association of fentanyl use in rapid sequence intubation with post-intubation
      hypotension.
AB  - BACKGROUND: The anesthesia literature has reported that pre-intubation fentanyl
      use is associated with post-intubation hypotension which is a risk factor of poor
      post-emergency department (ED) prognosis. However, little is known about the
      relations between fentanyl use for intubation and post-intubation hypotension in
      the ED. We aimed to determine whether pretreatment with fentanyl was associated
      with a higher risk of post-intubation hypotension in the ED. METHODS: We
      conducted a secondary analysis of data of ED airway management collected from a
      multicenter prospective study of 14 Japanese EDs from February 2012 through
      November 2016. We included all adult non-cardiac-arrest patients who underwent
      rapid sequence intubation for medical indication. Patients were divided into
      fentanyl and non-fentanyl groups. The primary outcome was post-intubation
      hypotension (systolic blood pressure <=90mmHg) in the ED. RESULTS: Of 1263
      eligible patients, 466 (37%) patients underwent pretreatment with fentanyl. The
      fentanyl group had a higher risk of post-intubation hypotension (17% vs. 6%;
      unadjusted OR, 1.73; 95%CI, 1.01-2.97; P=0.048) compared to the non-fentanyl
      group. In the multivariable analysis adjusting for age, sex, weight, principal
      indication, sedatives, intubator's specialty, number of intubation attempts, and
      patient clustering within EDs, the fentanyl group had a higher risk of post
      intubation hypotension (adjusted OR, 1.87; 95%CI, 1.05-3.34; P=0.03) compared to
      the non-fentanyl group. In the sensitivity analysis using propensity score
      matching, this association remained significant (OR, 3.17; 95%CI, 1.96-5.14;
      P<0.01). CONCLUSION: In this prospective multicenter study of ED airway
      management, pretreatment with fentanyl in rapid sequence intubation was
      associated with higher risks of post-intubation hypotension.

PMID- 29653791
TI  - Minimal Clinically Important Difference and Substantial Clinical Benefit After
      Revision Hip Arthroscopy.
AB  - PURPOSE: To define minimal clinically important difference (MCID) and substantial
      clinical benefit (SCB) in revision hip arthroscopy. METHODS: The modified Harris
      Hip Score (mHHS), the Hip Outcome Score (HOS), and the international Hip Outcome
      Tool (iHOT-33) were administered to revision hip arthroscopy patients. At 1 year
      postoperatively, patients graded their hip function based on anchor responses.
      SCB was defined as both a net change and an absolute value. Receiver operating
      characteristic analysis with area under the curve was used to confirm
      psychometric values. A distribution-based method was used for MCID. RESULTS:
      Forty-nine patients were included with a mean age of 29.7 (+/-8.6) years. The
      most common indication for revision hip arthroscopy was residual femoroacetabular
      impingement (FAI; N = 34; 69.4%) followed by capsular management (N = 8; 16.3%).
      At 1-year follow-up, 34 patients reported feeling improved. Outcome score change
      corresponding to MCID and SCB net change for the mHHS, HOS Activities of Daily
      Living (ADL), HOS Sports, and iHOT-33 was 7.9/23.1, 7.9/16.2, 13.1/25.0, and
      12.8/25.5, respectively. A higher proportion of patients with residual FAI
      achieved MCID compared with patients with other diagnoses. On the preoperative
      HOS ADL, HOS Sports, and iHOT-33, patients scoring below 67.7 (0.78), 55.6
      (0.81), and 35.7 (0.73) were significantly more likely to achieve SCB
      postoperatively. Thirty-four patients (73.9%) were classified as receiving
      physical function improvement, and on the HOS Sports, MCID was achieved by 65%
      whereas 43% met the SCB criteria. CONCLUSIONS: MCID values ranged from 7.9 on the
      mHHS and the HOS ADL to 13.1 on the HOS Sports. SCB net change ranged from 16.2
      on the HOS ADL to 25.2 on the iHOT-33, whereas absolute SCB ranged from 82.4 on
      the iHOT-33 to 84.7 on the mHHS. Residual FAI and capsular management were the
      most common indications for revision surgery with patients who underwent surgery
      for the former found to be most likely to achieve clinically significant
      improvement. LEVEL OF EVIDENCE: Level IV, case series.

PMID- 29653792
TI  - Arthroscopic Treatment of Iliopsoas Snapping in Patients With Radiographic
      Acetabular Dysplasia Using Iliopsoas Fractional Lengthening and Capsular
      Plication.
AB  - PURPOSE: The purpose of this study was to evaluate the greater than 2-year
      patient-reported outcomes (PROs) and patient satisfaction of patients who were
      treated with hip arthroscopy for snapping iliopsoas tendons that were painful
      with concomitant acetabular dysplasia and who underwent iliopsoas lengthening for
      symptomatic iliopsoas tendon snapping with concomitant capsular plication and
      treatment of hip impingement. Secondary measures included observation of the
      change in the Tonnis grade at greater than 2 years' follow-up. METHODS: Between
      July 2009 and December 2011, data on patients with a lateral center-edge angle
      (LCEA) of less than 25 degrees  (range, 19 degrees -24 degrees ) who underwent
      hip arthroscopy with central-compartment iliopsoas fractional lengthening and
      capsular plication were prospectively collected and retrospectively reviewed.
      Interportal capsular repair was performed using between 2 and 5 simple sutures.
      Patients also underwent procedures to treat hip impingement pathology. All
      patients had preoperative and minimum 2-year postoperative PRO measures: modified
      Harris Hip Score, Hip Outcome Score-Activities of Daily Living subscale, Hip
      Outcome Score-Sports-Specific subscale, and Non-arthritic Hip Score. The visual
      analog scale score and patient satisfaction with surgery (from 0 to 10) were also
      collected. Radiographs were analyzed preoperatively and at latest follow-up to
      assess progression of the Tonnis grade. RESULTS: We analyzed 32 patients who met
      the inclusion criteria (30 female and 2 male patients; mean age, 25 years). The
      mean LCEA and anterior center-edge angle were 21.6 degrees  and 25.5 degrees ,
      respectively. Four patients required revision arthroscopy for labral retears.
      Among the 28 patients who did not undergo revision surgery, the modified Harris
      Hip Score, Hip Outcome Score-Activities of Daily Living subscale, Hip Outcome
      Score-Sports-Specific subscale, and Non-arthritic Hip Score improved from 68.7 to
      83.5, from 64.9 to 86.6, from 71.6 to 86.7, and from 52.6 to 75.8, respectively
      (P < .001). The visual analog scale score improved from 5.6 preoperatively to 1.9
      at latest follow-up (P < .001). The mean patient satisfaction rating was 8.0.
      There was no radiographic progression of the Tonnis grade at final follow-up.
      CONCLUSIONS: This study showed that patients with an LCEA of less than 25 degrees
      and associated painful iliopsoas snapping can be treated by addressing
      concomitant pathology and performing central-compartment fractional lengthening
      of the iliopsoas tendon with concomitant capsular plication and have high
      satisfaction, improvement in PROs, and improved pain scores, without significant
      progression of osteoarthritis. LEVEL OF EVIDENCE: Level IV, case series.

PMID- 29653793
TI  - Medical Malpractice Litigation Following Arthroscopic Surgery.
AB  - PURPOSE: Our study aims to analyze a variety of factors involving malpractice
      lawsuits following arthroscopy, focusing on reasons for lawsuit and establishing
      predictors for the outcome of the lawsuit. METHODS: Two legal databases,
      VerdictSearch and Westlaw, were queried for arthroscopic cases in adult patients.
      For all included cases, clinical and demographic data were recorded. The effects
      of plaintiff demographics, joint involved, lawsuit allegation, case ruling, and
      size of indemnity payments were assessed. RESULTS: Of the 240 included cases, 62
      (26%) resulted in plaintiff verdict, 160 (67%) resulted in defense verdict, and
      18 (8%) were settled without trial. Plaintiff demographics (age and sex) had no
      effect on the case ruling. There was no statistical difference between indemnity
      awards for plaintiff verdicts ($1,013,494) and settled cases ($848,331; P = .13).
      Patient death was noted in 20 cases (8.3%); a significantly higher proportion of
      these cases were settled versus went to trial (P = .0022), including 19 patients
      (95%) who had knee arthroscopy and 16 deaths (80%) resulting from a pulmonary
      embolus. Plaintiff verdict or settlement were seen significantly more frequently
      for vascular complications and wrong-sided surgery. Alternatively, defense
      verdicts followed lawsuits alleging surgeon technical error. Wrong-sided surgery,
      retained instruments, deep venous thrombosis, and postoperative infections were
      seen at a significantly higher proportion after knee arthroscopy than after
      arthroscopy of other joints. Similarly, neurological injury was significantly
      associated with elbow and hip arthroscopy, while allegations of technical error
      by the surgeon and block-related complications were associated with shoulder
      arthroscopy. CONCLUSIONS: Plaintiff verdict or settlement were seen for vascular
      complications and wrong-sided surgery, while defense verdicts followed lawsuits
      alleging surgeon technical error and block-related complications. We also
      identified types of allegations that were associated with arthroscopy of
      different joints. All but one case of patient death (20 cases) were noted to
      involve knee arthroscopy, and an overwhelming majority resulted due to a
      pulmonary embolism. This information helps the arthroscopic surgeon better
      counsel patients and employ strategies to mitigate preventable complications.
      LEVEL OF EVIDENCE: Level IV, case series.

PMID- 29653794
TI  - Treatment for Symptomatic SLAP Tears in Middle-Aged Patients Comparing Repair,
      Biceps Tenodesis, and Nonoperative Approaches: A Cost-Effectiveness Analysis.
AB  - PURPOSE: To evaluate the cost-effectiveness of nonoperative management, primary
      SLAP repair, and primary biceps tenodesis for the treatment of symptomatic
      isolated type II SLAP tear. METHODS: A microsimulation Markov model was
      constructed to compare 3 strategies for middle-aged patients with symptomatic
      type II SLAP tears: SLAP repair, biceps tenodesis, or nonoperative management. A
      failed 6-month trial of nonoperative treatment was assumed. The principal outcome
      measure was the incremental cost-effectiveness ratio in 2017 U.S. dollars using a
      societal perspective over a 10-year time horizon. Treatment effectiveness was
      expressed in quality-adjusted life-years (QALY). Model results were compared with
      estimates from the published literature and were subjected to sensitivity
      analyses to evaluate robustness. RESULTS: Primary biceps tenodesis compared with
      SLAP repair conferred an increased effectiveness of 0.06 QALY with cost savings
      of $1,766. Compared with nonoperative treatment, both biceps tenodesis and SLAP
      repair were cost-effective (incremental cost-effectiveness ratio values of
      $3,344/QALY gained and $4,289/QALY gained, respectively). Sensitivity analysis
      showed that biceps tenodesis was the preferred strategy in most simulations
      (52%); however, for SLAP repair to become cost-effective over biceps tenodesis,
      its probability of failure would have to be lower than 2.7% or the cost of biceps
      tenodesis would have to be higher than $14,644. CONCLUSIONS: When compared with
      primary SLAP repair and nonoperative treatment, primary biceps tenodesis is the
      most cost-effective treatment strategy for type II SLAP tears in middle-aged
      patients. Primary biceps tenodesis offers increased effectiveness when compared
      with both primary SLAP repair and nonoperative treatment and lower costs than
      primary SLAP repair. LEVEL OF EVIDENCE: Level III, economic decision analysis.

PMID- 29653795
TI  - Arthroscopic Cartilage Lesion Preparation in the Human Cadaveric Knee Using a
      Curette Technique Demonstrates Clinically Relevant Histologic Variation.
AB  - PURPOSE: To examine the quality of arthroscopic cartilage debridement using a
      curette technique by comparing regional and morphologic variations within
      cartilage lesions prepared in human cadaveric knee specimens for the purpose of
      cartilage repair procedures. A secondary aim was to compare the histologic
      properties of cartilage lesions prepared by surgeons of varying experience.
      METHODS: Standardized cartilage lesions (8 mm * 15 mm), located to the
      medial/lateral condyle and medial/lateral trochlea were created within 12 human
      cadaver knees by 40 orthopaedic surgeons. Participants were instructed to create
      full-thickness cartilage defects within the marked area, shouldered by uninjured
      vertical walls of cartilage, and to remove the calcified cartilage layer, without
      violating the subchondral plate. Histologic specimens were prepared to examine
      the verticality of surrounding cartilage walls at the front and rear aspects of
      the lesions, and to characterize the properties of the surrounding cartilage, the
      cartilage wall profile, the debrided lesion depth, bone sinusoid access, and the
      bone surface profile. Comparative analysis of cartilage wall verticality measured
      as deviation from perpendicular was performed, and Spearman's rank correlation
      analysis was used to examine associations between debrided wall verticality and
      surgeon experience. RESULTS: Mean cartilage wall verticality relative to the base
      of the lesion was superior at the rear aspect of the lesion compared to the front
      aspect (12.9 degrees  vs 29.2 degrees , P < .001). Variability was identified in
      the morphology of the surrounding cartilage (P < .001), cartilage wall profile (P
      = .016), debrided lesion depth (P = .028), bone surface profile (P = .040), and
      bone sinusoid access (P = .009), with sinusoid access identified in 42% of cases.
      There was no significant association of cartilage lesion wall verticality and
      surgeon years in practice (rs = 0.161, P = .065) or arthroscopic caseload (rs = 
      0.071, P = .419). CONCLUSIONS: Arthroscopic cartilage lesion preparation using
      standard curette technique in a human cadaveric knee model results in inferior
      perpendicularity of the surrounding cartilage walls at the front aspect of the
      defect, compared to the rear aspect. This technique has shown significant
      variability in the depth of debridement, with debridement depths identified as
      either too superficial or too deep to the calcified cartilage layer in more than
      60% of cases in this study. Surgeon experience does not appear to impact the
      morphologic properties of cartilage lesions prepared arthroscopically using ring
      curettes. CLINICAL RELEVANCE: To optimize restoration of hyaline-like cartilage
      tissue, careful attention to prepared cartilage lesion morphology is advised when
      arthroscopically performing cartilage repair, given the tendency for standard
      curette technique to create inferior verticality of cartilage walls at the front
      of the lesion, and the variable depth of debridement achieved.

PMID- 29653796
TI  - Anatomic Tunnel Placement Is Not Feasible by Transclavicular-Transcoracoid
      Drilling Technique for Coracoclavicular Reconstruction: A Cadaveric Study.
AB  - PURPOSE: To evaluate the feasibility of anatomic tunnel placement by a
      transclavicular-transcoracoid drilling technique and with reference to the
      coracoclavicular ligaments' insertional anatomy and their orientations. METHODS:
      We used 12 fresh-frozen human cadaveric shoulders (6 matched pairs; mean age, 70
      years; age range, 51-82 years) to simulate intraoperative tunnel placement with
      the transclavicular-transcoracoid drilling technique. After both the conoid and
      trapezoid ligaments were identified, two 2.5-mm guide pins were inserted from the
      clavicle to the coracoid, passing the centers of the clavicular and coracoid
      insertions of the conoid and the trapezoid ligaments, in a collinear fashion to
      the orientation of both ligaments. The entry point of the drill at the clavicle
      and the exit point at the coracoid undersurface, as well as the tunnel
      orientations, were measured. Complications due to the procedure, including a
      breach of the bone cortex of the clavicle and/or coracoid process, were recorded.
      RESULTS: The transclavicular-transcoracoid drilling technique for anatomic conoid
      ligament tunnel placement resulted in a medial cortical breach at the coracoid
      process in 6 of 12 shoulders. In the remaining 6 shoulders without a breach, the
      distance of the exit point from the medial cortex of the inferior coracoid
      process was only 3.6 +/- 4.3 mm. For anatomic trapezoid ligament tunnel
      placement, no medial cortex breaching at the coracoid process occurred. However,
      the distance of the exit point was 3.1 +/- 4.2 mm, indicating an eccentric
      location to the medial cortex of the coracoid process, similar to the conoid
      ligament. CONCLUSIONS: This cadaveric study showed that anatomic tunnel placement
      by the transclavicular-transcoracoid drilling technique would not be feasible
      without breaching or almost breaching the medial cortex of the coracoid process.
      CLINICAL RELEVANCE: The transclavicular-transcoracoid drilling technique for CC
      ligament reconstruction may not reproduce the anatomy of the CC ligaments but may
      place the coracoid process at high risk of fracture during tunnel placement.

PMID- 29653797
TI  - Association Between Ethnicity and Postoperative Hyperglycemia in a Southeast
      Asian Population Undergoing Cardiac Surgery.
AB  - OBJECTIVE: Postoperative hyperglycemia is a known risk factor for adverse
      outcomes following cardiac surgery. Therefore, the authors investigated the
      association between ethnicity and postoperative hyperglycemia in a Southeast
      Asian multiethnic population undergoing cardiac surgery. DESIGN: Perioperative
      data were analyzed prospectively. SETTING: Perioperative data were obtained from
      2008 to 2010 at the 2 main heart centers in Singapore. PARTICIPANTS: Data from
      911 adult patients were collected. INTERVENTIONS: All patients underwent elective
      cardiac surgery. MEASUREMENTS AND MAIN RESULTS: Perioperative variables, genetic
      associations, and outcomes of hyperglycemic versus normoglycemic patients were
      compared. Of the 911 patients analyzed, 47.7% (n = 435) were diabetic and 77.7%
      (n = 708) had postoperative hyperglycemia. Patients with postoperative
      hyperglycemia after cardiac surgery were more likely to have diabetes; be female,
      older, and more obese; and have hypertension and renal impairment. Patients of
      Indian ethnicity had a significantly higher incidence of postoperative
      hyperglycemia (86.7%, p = 0.043), as compared to Malays (79.1%) and Chinese
      (75.9%). Ethnicity was identified as an independent risk factor for postoperative
      hyperglycemia, with Indians having a significantly higher risk than Chinese (OR
      2.115, p = 0.015). Although Indian ethnicity was associated with the presence of
      angiotensin-converting enzyme D allele (65.7%, p = 0.044), no genetic
      associations with postoperative hyperglycemia were identified. Postoperative
      hyperglycemia also was associated significantly with poorer outcomes of longer
      high-dependency unit stay and new-onset cardiac arrhythmias. CONCLUSION: The
      authors' findings demonstrated Indian ethnicity as an independent risk factor of
      postoperative hyperglycemia, likely due to insulin resistance and exaggerated
      hyperglycemic stress response, emphasizing the need for ethnic-based data unique
      to each population group.

PMID- 29653798
TI  - Identification of Leishmania (Viannia) species and clinical isolates of
      Leishmania (Leishmania) amazonensis from Brazil using PCR-RFLP of the heat-shock
      protein 70 gene reveals some unexpected observations.
AB  - Hsp70 is a cytoplasmic heat-shock protein, encoded by a multicopy tandemly
      repeated gene that has recently been gaining popularity as a valuable marker for
      typing Leishmania species. In this study, we used a previously described hsp70
      PCR-RFLP method for identifying Brazilian Leishmania isolates. We identified two
      distinct L. (L.) amazonensis hsp70 alleles that resulted in two different RFLP
      patterns. Also, we found RFLP polymorphisms amongst L. (Viannia) naiffi strains.
      The profiles of both L. (V.) shawi and L. (V.) lindenbergi were very similar to
      those of other L. (Viannia) species. The observations described herein reflect
      the polymorphism found within species of Leishmania and indicate that results
      from this hsp70 PCR-RFLP method should be used with caution when typing isolates
      from clinical cases of leishmaniasis and Leishmania species from Brazil.

PMID- 29653799
TI  - Factors associated with pregnancy intention among women who have experienced a
      short birth interval: findings from the 2009 to 2011 Mississippi and 2009
      Tennessee Pregnancy Risk Assessment Monitoring System.
AB  - PURPOSE: One-third of all pregnancies in the United States are conceived within
      18 months of a prior live birth. Preventing unintended pregnancies may help to
      decrease the prevalence of pregnancies with these short interpregnancy intervals.
      However, data on factors associated with pregnancy intention among women who have
      had short birth intervals are sparse. Pregnancy Risk Assessment Monitoring System
      data were used to further evaluate these associations. METHODS: Because only
      Mississippi and Tennessee Pregnancy Risk Assessment Monitoring System include a
      survey question about birth interval length, this analysis was limited to women
      from those states who recently had a short birth interval (n = 384). Pregnancy
      intention and demographic, lifestyle, and reproductive data were obtained from
      surveys and birth certificates. Logistic regression was used to obtain odds
      ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Nearly 76% of women
      with short birth intervals reported their pregnancy as unintended. Women who were
      non-Hispanic black or consumed alcohol during pregnancy had statistically
      significant increased odds of reporting the pregnancy with a short birth interval
      as being unintended (OR = 3.98; 95% CI: 1.73-9.16 and OR = 10.56; 95% CI: 1.80
      61.83, respectively). CONCLUSIONS: Although all women should be counseled on
      postpartum contraceptive use, findings suggest that important subpopulations of
      women may benefit from more targeted counseling during prenatal care visits and
      the immediate postpartum hospital stay regarding the importance of using
      contraception to not only better space pregnancies but also prevent unintended
      pregnancies.

PMID- 29653800
TI  - Use of supplemental oxygen in patients with pulmonary arterial hypertension in
      REVEAL.
AB  - BACKGROUND: Supplemental low-flow oxygen is recommended by treatment guidelines
      as supportive therapy for patients with pulmonary arterial hypertension (PAH),
      based largely on expert opinion. Reduced diffusing capacity of lung carbon
      monoxide (DLCO) is associated with increased mortality in PAH. Reduced DLCO is
      also associated with relative hypoxemia, making the effects of supplemental
      oxygen use of particular interest in this sub-population. METHODS: Patients in
      the Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL), a 5
      year observational study of Group 1 PAH, were categorized by presence or absence
      of supplemental oxygen use and by degree of DLCO reduction. Kaplan-Meier survival
      estimates were calculated by group. RESULTS: Of 3,046 patients, 57% used
      supplemental oxygen and 43% did not. Supplemental oxygen users had worse
      prognostic factors and more PAH-specific medication use. Of the 424 patients with
      severe DLCO reduction (<40% of predicted), 76% used oxygen and 24% did not.
      Patients with severe DLCO reduction who used supplemental oxygen had a
      significantly lower risk of all-cause mortality than those who did not (hazard
      ratio 0.56; 95% confidence interval 0.39 to 0.83; p = 0.0033). This was true for
      newly diagnosed and previously diagnosed patients. There was no relationship
      between oxygen use and outcomes in patients with no, mild, or moderate DLCO
      reduction. CONCLUSIONS: In this observational study, the risk of death was
      significantly lower for patients with severe DLCO reduction who received
      supplemental oxygen compared with those who did not. A randomized trial is
      warranted to further investigate the relationship between supplemental oxygen use
      and outcomes in PAH.

PMID- 29653801
TI  - Impact of MaxZeroTM needle-free connector on the incidence of central venous
      catheter-related infections in surgical intensive care unit.
AB  - BACKGROUND: Central venous catheter-related infections (CRIs) are a complication
      of central venous catheters in intensive care unit (ICU). Some needle-free
      connectors have been designed to decrease CRI, but there is a lack of data
      concerning their impact on infection. OBJECTIVES: The objective was to explore
      the impact of MaxZeroTM connectors (BD; Franklin Lakes, US) on CRI in ICU.
      METHODS: Observational, pre-post design study (2011-2013 and 2014-2016) conducted
      in the surgical ICU of a tertiary care hospital (18 beds). Patients with a
      central venous catheter and a length of stay >=48 h were included. The connectors
      replaced all disposable caps used on infusion stopcocks and ramps. The primary
      parameter was to compare the incidence of CRI between the "before" period and the
      "after" period. RESULTS: A total of 1633 patients were included (789 "before" and
      844 "after"). There was no difference between groups concerning the global
      duration of catheterisation (12.5 +/- 11.5 days vs. 12.1 +/- 10.9 days). There
      were 61 CRIs before and 28 CRIs after the introduction of connectors; the
      incidence of CRI in the "before" group was 20.33 CRI/year (6.18 CRI per 1000
      catheter-days) vs. 9.33 CRI/year (2.73 CRI per 1000 catheter-days) in the "after"
      group (incidence rate ratio = 0.44; 95% confidence interval = 0.28-0.68, p <
      0.001). However, after a global analysis of the 6-year period, when adjusting for
      seasonal effect and pre-existing linear trend, the effect was no longer
      significant (adjusted incidence rate ratio = 0.57; 95% confidence interval = 0.24
      1.35, p = 0.20). CONCLUSIONS: Our results do not allow us to conclude to a
      potential beneficial effect of MaxZeroTM on CRI but are compatible with its
      prolonged and safe use in ICU. Only future prospective works will be able to
      confirm the value of these connectors for CRI prevention.

PMID- 29653802
TI  - The Impacts of Peptic Ulcer on Stroke Recurrence.
AB  - BACKGROUND: Peptic ulcer has been associated with an increased risk of stroke.
      This study aimed to evaluate the impacts of peptic ulcer on stroke recurrence and
      mortality. SUBJECTS AND METHODS: Patients with first-ever ischemic stroke were
      retrospectively confirmed with or without a history of peptic ulcer. The primary
      end point was defined as fatal and nonfatal stroke recurrence. Risks of 1-year
      fatal and nonfatal stroke recurrence were analyzed with the Kaplan-Meier method.
      Predictors of fatal and nonfatal stroke recurrence were evaluated with the Cox
      proportional hazards model. RESULTS: Among the 2577 enrolled patients with
      ischemic stroke, 129 (5.0%) had a history of peptic ulcer. The fatal and nonfatal
      stroke recurrence within 1 year of the index stroke was higher in patients with
      peptic ulcer than in patients without peptic ulcer (12.4% versus 7.2%, P = .030).
      Cox proportional hazards model detected that age (hazard ratio [HR] = 1.018, 95%
      confidence interval [CI] 1.005-1.031, P = .008), hypertension (HR = 1.397, 95% CI
      1.017-1.918, P = .039), and history of peptic ulcer (HR = 1.853, 95% CI 1.111
      3.091, P = .018) were associated with stroke recurrence. CONCLUSIONS: Ischemic
      stroke patients with peptic ulcer may have an increased risk of stroke
      recurrence. The results emphasize the importance of appropriate prevention and
      management of peptic ulcer for secondary stroke prevention.

PMID- 29653803
TI  - Unique Angiographic Appearances of Moyamoya Disease Detected with 3-Dimensional
      Rotational Digital Subtraction Angiography Imaging Showing the Hemodynamic
      Status.
AB  - BACKGROUND: The aim of this study was to identify the unique morphological
      arterial features in patients with moyamoya disease on 3-dimensional rotational
      digital subtraction angiography. MATERIALS AND METHODS: One hundred seven
      hemispheres of 58 consecutive patients with moyamoya disease that were analyzed
      with fused 3-dimensional images of internal carotid angiograms and vertebral
      angiograms that were marked with different colors were reviewed. Angiographic
      findings in the posterior watershed area were classified, and the utility of the
      classification was analyzed by comparing it with clinical presentations and
      quantitative hemodynamic parameters obtained with positron emission tomography.
      RESULTS: Two unique angiographic appearances were identified. A vacant vessel
      appearance (no arterial inflow despite absence of cortical infarction) was
      observed mostly in transient ischemic attack hemispheres. In hemispheres with a
      vacant vessel appearance, cerebral blood flow was decreased, cerebral blood
      volume was increased, and mean transit time was prolonged significantly (P =
      .00017, P = .0061, and P = .00026, respectively). A cocktail vessel appearance
      (mixture of carotid and vertebral arterial flow) was most commonly observed in
      asymptomatic cases, as well as in ischemic hemispheres. Cerebral blood volume
      increased and mean transit time was prolonged significantly (P = .036 and P =
      .014, respectively) in hemispheres with a cocktail vessel appearance. The trend
      of progression in hemodynamic severity in the order of normal appearance,
      cocktail vessel appearance, and vacant vessel appearance in the watershed area
      was statistically significant. CONCLUSION: Fused 3-dimensional digital
      subtraction angiography demonstrated unique angiographic features in the
      watershed area, and this represented the degree of cerebral hemodynamic
      impairment in moyamoya disease.

PMID- 29653804
TI  - Urgent Detection of Acute Type A Aortic Dissection in Hyperacute Ischemic Stroke
      or Transient Ischemic Attack.
AB  - BACKGROUND AND PURPOSE: Urgent diagnosis of acute Stanford type A aortic
      dissection (AAD) in patients with acute ischemic stroke (AIS) or transient
      ischemic attack (TIA) is sometimes challenging. We assessed predictive values for
      markers of AAD in patients with AIS or TIA. METHODS: Consecutive patients with
      AIS or TIA with AAD who presented to our emergency room within 4.5 hours of
      symptom onset between 2007 and 2014 were compared with patients without AAD seen
      between 2012 and 2014. RESULTS: Data were obtained for 24 patients with AIS or
      TIA with AAD (15 women; mean age, 75 +/- 12 years) and 812 patients without AAD
      (305 women; mean age, 73 +/- 12 years). Compared with patients without AAD,
      patients with AAD displayed significantly higher systolic blood pressure (SBP)
      laterality (30 +/- 20 mm Hg versus 12 +/- 11 mm Hg), initial D-dimer
      concentration (median 38.1 ug/mL versus 1.3 ug/mL), and mediastinal width-to
      chest width (M/C) ratio on x-ray (.35 +/- .05 versus .29 +/- .05), and more
      frequently showed common carotid artery (CCA) dissection on carotid
      ultrasonography (84% versus 1%) and pericardial effusion on echocardiography (43%
      versus 0%). Sensitivity and specificity to identify AAD were 80% and 75% for SBP
      laterality 17 mm Hg or greater; 100% and 86% for D-dimer concentration 4.1 ug/mL
      or greater; 75% and 76% for M/C ratio .32 or greater; 84% and 99% for CCA
      dissection; and 43% and 100% for pericardial effusion, respectively. CONCLUSIONS:
      High D-dimer level may provide the most reliable screening test for AAD in
      patients with AIS or TIA. CCA dissection on ultrasonography appears to represent
      the most disease-specific finding and shows acceptable sensitivity.

PMID- 29653806
TI  - Fake medicines: fighting on all fronts.

PMID- 29653805
TI  - Intravenous Thrombolysis for Stroke Patients with G6PD Deficiency.
AB  - BACKGROUND AND PURPOSE: No reports regarding the safety of thrombolysis in acute
      stroke patients with a G6PD deficiency have been published to date. Here we aimed
      to evaluate the safety of intravenous thrombolysis for G6PD-deficient stroke
      patients. METHODS: We enrolled each patient with acute ischemic stroke who
      arrived in our stroke unit within the therapeutic window and received systemic
      thrombolysis using recombinant tissue plasminogen activator (rt-PA), between
      January 2015 and March 2016. The primary clinical outcome was measured 3 months
      after treatment, and defined as a "good" outcome by a modified Rankin Scale (mRS)
      score of 0-2. Major safety outcomes were incidences of intracranial hemorrhage
      (ICH) or mortality at 90 days. RESULTS: A total of 96 individuals were analyzed,
      of which 20 patients were G6PD deficient. The rates of ICH after rt-PA treatment
      were 12% the in G6PD-deficient group versus 15% in G6PD non-deficient group, and
      the incidences of symptomatic intracranial hemorrhage were also similar between
      the G6PD-deficient and non-deficient cohorts. No hemolysis crisis occurred, and
      no significant difference in mortality rate was found between the 2 groups. The
      overall rate of a good outcome at 3 months after stroke in the whole cohort was
      60%, whereas 50% of patients achieved an excellent outcome (mRS 0-1) in the G6PD
      deficient cohort, and 42% in the G6PD non-deficient group. CONCLUSIONS:
      Thrombolytic therapy for patients with G6PD deficiency seems to pose a similar
      risk of ICH and clinical outcome to those with G6PD non-deficiency.

PMID- 29653807
TI  - HEROs: Design of a Mixed-Methods Formative Research Phase for an Ecocultural
      Intervention to Promote Healthy Eating and Activity Behaviors in Rural Families
      With Preschoolers.
AB  - OBJECTIVE: To describe the mixed-methods formative research phase in the
      development of the Healthy Environments Study (HEROs), a technology-based,
      interactive family intervention to promote healthy eating and activity behaviors
      for young children in the home environment. DESIGN: A mixed-method iterative
      approach, using ecocultural theory as a framework, will guide the development of
      both quantitative and qualitative formative research assessments. SETTING: Rural
      eastern Colorado. PARTICIPANTS: Low-income families (n = 200) with preschool-aged
      children enrolled at 6 Head Start/preschool centers. MAIN OUTCOME MEASURES:
      Quantitative and qualitative methodologies will garner insights into 4 key topic
      areas: (1) food behaviors and environments (Remote Food Photography Method,
      parent focus group, and survey), (2) physical activity behaviors and environments
      (parent interview and survey), (3) mobile device use (parent survey and
      interview), and (4) daily life (ecocultural family interview and teacher/staff
      group discussions). ANALYSIS: Results will be interpreted in combination to allow
      for a holistic understanding of participant behaviors, beliefs, attitudes and
      values related to each of the 4 topic areas. Collectively, outcomes will provide
      a comprehensive picture of preschoolers' daily life and inform intervention
      design and strategies to enhance preschoolers' eating and activity behaviors in
      the home environment.

PMID- 29653808
TI  - The AO international fellowship: South American perspective of a career changing
      experience.

PMID- 29653809
TI  - Process Evaluation of an Intervention for the Management of Neuropsychiatric
      Symptoms in Young-Onset Dementia.
AB  - OBJECTIVES: A process evaluation was performed for an intervention aimed at
      improvement of the management of neuropsychiatric symptoms in young-onset
      dementia. Data about sample quality and intervention quality was evaluated to
      better understand internal and external validity. In addition, data about the
      implementation strategy and factors affecting implementation were evaluated to
      improve further implementation of the intervention. DESIGN: A model proposed by
      Leontjevas and colleagues consisting of first-order (validity) and second-order
      (implementation) data was used. SETTING AND PARTICIPANTS: Care units delivering
      specialized treatment and support for residents with young-onset dementia.
      MEASURES: A description of the recruitment, randomization procedure, and
      intervention reach was carried out to determine sample quality. To determine
      intervention quality, data on satisfaction, relevance, feasibility, and fidelity
      were collected through a questionnaire and reports logged on the server of the
      web-based intervention. A description of the implementation strategy was
      provided. Barriers and facilitators for implementation were collected by a
      questionnaire and analyzed by deductive content analysis. RESULTS: Care units
      varied in size and were recruited from different geographical regions in the
      Netherlands. The informed consent rate of the residents was 87.7%. The majority
      of the nursing home staff were satisfied with the intervention. However, parts of
      the intervention were perceived as less relevant for their own organization. The
      feasibility of the intervention was considered low. The fidelity differed between
      care units. The implementation strategy did not overcome all barriers. Factors
      affecting implementation covered 3 themes: organizational aspects, culture of the
      organization, and aspects of the intervention. CONCLUSIONS: In general, our
      results showed sufficient internal and external validity, warranting further
      effect analyses. Adaptations to specific steps of the care program should be
      considered to increase feasibility and sustainability. In addition, integration
      of the care program into the electronic health records is expected to further
      improve implementation.

PMID- 29653811
TI  - Correction to Lancet Diabetes Endocrinol 2018; 6: 809-20.

PMID- 29653810
TI  - Urban-Rural Differences in Skilled Nursing Facility Rehospitalization Rates.
AB  - OBJECTIVES: To examine the association of rurality with skilled nursing facility
      (SNF) all-cause 30-day risk-adjusted rehospitalization rates. DESIGN: Cross
      sectional study combining Center for Medicare and Medicaid Services Nursing Home
      Compare (CMS-NHC) website for 30-day risk-adjusted rehospitalization rates for
      2014-2015 with SNF organizational and community variables. PARTICIPANTS: 12,261
      non-hospital based skilled nursing facilities in the US. MEASUREMENTS: We
      estimated a multiple linear regression model of percentage all-cause unplanned
      risk-adjusted rehospitalization rate within 30 days after a hospital discharge
      and admission to the SNF averaged over the third and fourth quarters of 2014 and
      the first and second quarters of 2015. The model uses robust standard errors.
      RESULTS: After controlling for community- and SNF-level resources, the risk
      adjusted rehospitalization rates for SNFs are lowest in rural areas and large
      rural towns followed by SNFs in suburban and then urban areas. CONCLUSION: The
      rural culture that includes a strong sense of connectedness among residents may
      contribute to lower SNF rehospitalization rates. Our results suggest that rural
      SNFs may avoid future reimbursement penalties and decreased admissions from
      patients discharged from hospitals because of their lower rehospitalizaton rates.
      However, because this is the first study to address this topic, additional
      research is needed.

PMID- 29653812
TI  - Vitamin D supplementation and lipoprotein metabolism: A randomized controlled
      trial.
AB  - BACKGROUND: Vitamin D deficiency is associated with an unfavorable lipid profile,
      but whether and how vitamin D supplementation affects lipid metabolism is
      unclear. OBJECTIVE: To examine the effects of vitamin D supplementation on lipid
      and lipoprotein parameters. METHODS: This is a post hoc analysis of the single
      center, double-blind, randomized, placebo-controlled Styrian Vitamin D
      Hypertension Trial (2011-2014). Two hundred individuals with arterial
      hypertension and 25-hydroxyvitamin D concentrations of <75 nmol/L were randomized
      to 2800 IU of vitamin D daily or placebo for 8 weeks. RESULTS: One hundred sixty
      three participants (62.2 [53.1-68.4] years of age; 46% women) had available lipid
      data and were included in this analysis. Vitamin D supplementation significantly
      increased total cholesterol, triglycerides, very-low-density lipoprotein (VLDL)
      triglycerides, low-density lipoprotein (LDL) triglycerides, high-density
      lipoprotein (HDL) triglycerides, apolipoprotein B (ApoB), LDL-ApoB, ApoCII,
      ApoCIII, phospholipids, and ApoE (P < .05 for all). Except for ApoCII and ApoCIII
      and HDL-triglycerides, all other treatment effects remained statistically
      significant after adjustment for multiple testing with the Benjamini and Hochberg
      false discovery rate method. There was a nonsignificant increase in LDL
      cholesterol. Furthermore, no significant effects were seen on free fatty acids,
      lipoprotein (a), ApoAI, ApoAII, VLDL cholesterol, VLDL-ApoB, HDL cholesterol, LDL
      diameter, and VLDL diameter. CONCLUSIONS: The effects of vitamin D on lipid
      metabolism are potentially unfavorable. They require further investigation in
      view of the wide use of vitamin D testing and treatment.

PMID- 29653813
TI  - Predictors of Long-Term Response With Pazopanib in Patients With Advanced Renal
      Cell Carcinoma.
AB  - BACKGROUND: Pazopanib is among the current standards of care for first-line
      treatment of patients with unresectable advanced renal-cell carcinoma (aRCC) or
      metastatic renal-cell carcinoma. This real-world study aimed to characterize
      those with long-term response to pazopanib in the treatment of aRCC in a
      community oncology setting, and to identify predictors of long-term response.
      PATIENTS AND METHODS: aRCC patients treated with first-line pazopanib were
      classified as having long-term or non-long-term response (progression-free
      survival [PFS] of >= 18 or < 18 months, respectively). Baseline patient
      demographics and clinical characteristics were evaluated and compared between the
      2 groups. Differences in PFS and overall survival were also evaluated. RESULTS: A
      total of 153 eligible patients were identified, of which 33 (21.6%) and 120
      (78.4%) patients were identified as having disease with long-term and non-long
      term response, respectively. The median PFS for those with long-term response was
      27.2 months (95% confidence interval [CI], 23.0-35.2) versus 6.9 months (95% CI,
      5.0-8.6) for those with non-long-term response. Median overall survival was not
      reached (NR) for those with long-term response (95% CI, NR to 39.1) compared to
      15.3 months (95% CI, 12.3-21.6) for those with non-long-term response. Baseline
      Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 (vs. ECOG PS
      of 1 and >= 2) and history of nephrectomy were identified as significant
      predictors of long-term response to pazopanib. CONCLUSION: In aRCC patients
      treated with first-line pazopanib, 22% had a long-term response. Significant
      predictors of long-term response included an ECOG PS of 0 and a history of
      nephrectomy.

PMID- 29653814
TI  - Predictors of Cancer-specific Survival After Disease Recurrence in Patients With
      Renal Cell Carcinoma: The Effect of Time to Recurrence.
AB  - INTRODUCTION: A few studies addressed predictive factors of cancer-specific
      mortality (CSM) in patients with recurrent renal cell carcinoma (RCC) following
      surgery. Time to recurrence (TTR) is an important predictor of CSM in various
      types of cancers. The aim of our study was to describe the course of RCC
      following disease recurrence and to identify prognostic factors that influence
      CSM with a special focus on TTR. MATERIALS AND METHODS: Retrospective analysis of
      331 patients who experienced disease recurrence after radical nephrectomy (n =
      307) or partial nephrectomy (n = 24) with curative intent. A Cox proportional
      hazards regression model addressed the association between various
      clinicopathologic features and CSM after disease recurrence. TTR was defined as
      time from surgery to occurrence of disease recurrence. RESULTS: Of the 331
      patients, 232 (70%) were male, and 99 (30%) were female. The median age at
      surgery was 62 years (interquartile range, 53-69 years). Median time from
      nephrectomy to disease recurrence was 1.2 years (interquartile range, 0.5-3.3
      years). Of the recurrences, 63 (19%) were local, and 268 (81%) were distant.
      Shorter time to recurrence (P = .0008), female gender (P = .035), and distant
      versus local recurrence location (P < .0001) were found to be independently
      associated with CSM following disease recurrence. CONCLUSIONS: In patients
      experiencing disease recurrence after nephrectomy for presumably localized RCC,
      shorter TTR, female gender, and distant recurrence were found to be associated
      with worse CSM. The inclusion of these factors into risk-stratification tools may
      help patient counseling and decision-making regarding type and regimen of salvage
      treatment.

PMID- 29653816
TI  - An ulcer on the ventral tip of tongue.

PMID- 29653815
TI  - Matrix-associated chondrocyte transplantation for reconstruction of articulating
      surfaces in the temporomandibular joint: a pilot study covering medium- and long
      term outcomes of 6 patients.
AB  - OBJECTIVE: Matrix-associated chondrocyte transplantation is routinely used in
      joints of the extremities but not in the temporomandibular joint (TMJ). STUDY
      DESIGN: We report the first case series in 7 patients of a tissue engineering
      approach to regenerate severely degraded articulating surfaces in the TMJ by
      simultaneously completely resurfacing both the mandibular condyle and the
      articular eminence/glenoid fossa with a commercially available collagen sponge
      seeded with autologous cells stabilized within a fibrin matrix. To facilitate
      healing, we temporarily employed a silicone membrane to protect the engineered
      tissues. The indications for surgery were posttraumatic fibro-osseous ankylosis,
      ankylosing osteoarthritis, or late-stage osteoarthritis. RESULTS: Six of the
      patients were recalled for follow-up after 3 years 6 months to 12 years 1 month.
      The maximum incisal opening was 18.2 +/- 9.2 mm (range, 9-33 mm) before and 31.2
      +/- 13.6 mm (range, 12-47 mm) at the latest follow-up. Histologic specimens taken
      at 4 months showed beginning differentiation of fibrocytes into chondrocytes,
      whereas at 3 and 11 years, mature hyaline cartilage-not typical for the TMJ-was
      present. CONCLUSIONS: We conclude that the reconstruction of TMJ surfaces by
      matrix-associated chondrocyte transplantation may become a routine method for
      cartilage regeneration in the TMJ in the future.

PMID- 29653817
TI  - [Radiation therapy in patients with inflammatory bowel disease. A review].
AB  - Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative
      colitis, are multifactorial diseases characterized by a chronic intestinal
      inflammation. Abdominal and pelvic irradiation can result in acute or chronic
      digestive toxicity. A few old studies on small population samples have suggested
      an increase of gastro-intestinal toxicities in patients with IBD in case of
      irradiation. Nevertheless, the physiopathology is unknown. More recent studies,
      including new irradiation techniques, have shown less toxicity events in these
      patients with IBD. There are no recommendations for irradiation in patients with
      IBD. This review aims to report recent data on this topic and discuss them
      regarding radiation parameters.

PMID- 29653818
TI  - Corrigendum to "The enhancement and inhibition of mercury reduction by natural
      organic matter in the presence of Shewanella oneidensis MR-1" [Chemosphere 194,
      (March 2018) 515-522].

PMID- 29653819
TI  - Update on International Cooperative Groups Studies in Thoracic Malignancies: The
      Emergence of Immunotherapy.
AB  - Cancer cooperative groups have historically played a critical role in the
      advancement of non-small-cell lung cancer therapy. Representatives from
      cooperative groups worldwide convene at the International Lung Cancer Congress
      annually. The International Lung Cancer Congress had its 17th anniversary in the
      summer of 2016. The present review highlights the thoracic malignancy studies
      discussed by presenters. The included studies are merely a sample of the trials
      of thoracic malignancies ongoing globally.

PMID- 29653820
TI  - Afatinib as First-line Treatment of Older Patients With EGFR Mutation-Positive
      Non-Small-Cell Lung Cancer: Subgroup Analyses of the LUX-Lung 3, LUX-Lung 6, and
      LUX-Lung 7 Trials.
AB  - BACKGROUND: Afatinib is approved in the US, Europe, and several other regions for
      first-line treatment for epidermal growth factor receptor mutation-positive
      (EGFRm+) non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Treatment
      naive patients with advanced EGFRm+ NSCLC were randomized to afatinib (40 mg/d)
      versus cisplatin/pemetrexed (LUX-Lung 3 [LL3]) or cisplatin/gemcitabine (LUX-Lung
      6 [LL6]), or versus gefitinib (250 mg/d; LUX-Lung 7 [LL7]). We report subgroup
      analyses according to age, including 65 years or older versus younger than 65
      years (preplanned; LL3/LL6) and additional cutoffs up to 75 years and older
      (exploratory; LL7). Progression-free survival (PFS), overall survival (OS), and
      adverse events (AEs) were evaluated. RESULTS: Among the 134 of 345 (39%) and 86
      of 364 (24%) patients aged 65 years and older in LL3 and LL6, median PFS was
      improved with afatinib versus chemotherapy (LL3: hazard ratio [HR], 0.64 [95%
      confidence interval (CI), 0.39-1.03]; LL6: HR, 0.16 [95% CI, 0.07-0.39]).
      Afatinib significantly improved OS versus chemotherapy in elderly patients with
      Del19+ NSCLC in LL3 (HR, 0.39 [95% CI, 0.19-0.80]). Among the 40 of 319 patients
      (13%) aged 75 years or older in LL7, median PFS (HR, 0.69 [95% CI, 0.33-1.44])
      favored afatinib, consistent with the overall population. Afatinib-associated AEs
      in older patients were consistent with the overall populations. CONCLUSIONS:
      Subgroup analyses of the LL3, LL6, and LL7 trials show that afatinib is an
      effective and tolerable treatment for patients with EGFRm+ NSCLC, independent of
      age.

PMID- 29653821
TI  - Physician-Assisted Death Psychiatric Assessment: A Standardized Protocol to
      Conform to the California End of Life Option Act.
AB  - BACKGROUND: The California End of Life Option Act (EOLOA), which legalized
      physician-assisted death (PAD), became effective in 2016. The EOLOA does not
      require a mental health consultation in all cases nor does it state the standards
      for the mental health assessment. University of California, San Francisco Medical
      Center (UCSFMC) policy makers decided to require a mental health assessment of
      all patients seeking PAD under the EOLOA. OBJECTIVES: The Department of
      Psychiatry was tasked with developing a standard protocol for the mental health
      assessment of patients seeking PAD. METHODS: Members of the consultation-liaison
      (C-L) service developed a document to guide members in completing the mental
      health evaluations for patients requesting PAD. RESULTS: A committee at UCSFMC
      developed a clinical protocol informed by the law with an additional local
      expectation of an evaluation by a psychiatrist or clinical psychologist. The C-L
      psychiatry group at UCSF developed a standard protocol for the psychiatric
      assessment for use by clinicians performing these assessments. Attention to the
      cognitive, mood, and decisional capacity status pertinent to choosing PAD is
      required under the clinical guidance document. Case vignettes of 6 patients
      evaluated for PAD are presented. CONCLUSIONS: The local adoption of the
      California EOLOA by UCSFMC requires a mental health assessment of all patients
      requesting EOL services at UCSF. The clinical guideline for these assessments was
      locally developed, informed by the literature on EOL in other jurisdictions where
      it has already been available.

PMID- 29653822
TI  - Robust Frankia phylogeny, species delineation and intraspecies diversity based on
      Multi-Locus Sequence Analysis (MLSA) and Single-Locus Strain Typing (SLST)
      adapted to a large sample size.
AB  - Diazotrophic Actinobacteria of the genus Frankia represent a challenge to
      classical bacterial taxonomy as they include many unculturable strains. As a
      consequence, we still have a poor understanding of their diversity, evolution and
      biogeography. In this study, a Multi-Locus Sequence Analysis (MLSA) using atpD,
      dnaA, ftsZ, pgk, and rpoB loci was done on a large set of cultured and uncultured
      strains, compared to 16S rRNA and correlated to Average Nucleotide Identity (ANI)
      from available Frankia genomes. MLSA provided a robust resolution of Frankia
      genus phylogeny and clarified the status of unresolved species and complex of
      species. The robustness of single-gene topologies and their congruence with the
      MLSA tree were tested. Lateral Gene Transfers (LGT) were few and scattered,
      suggesting they had no impact on the concatenate topology. The pgk marker -
      providing the longest sequence, highest mean genetic divergence and least
      occurrence of LGT - was used to survey an unequalled number of Alnus-infective
      Frankia - mainly uncultured strains from a broad range of host-species and
      geographic origins. This marker allowed reliable Single-Locus Strain Typing
      (SLST) below the species level, revealed an undiscovered taxonomical diversity,
      and highlighted the effect of cultivation, sporulation phenotype and host plant
      species on symbiont richness, diversity and phylogeny.

PMID- 29653823
TI  - "Society of Hematologic Oncology (SOHO) State of the Art Updates and Next
      Questions"-Treatment of ALL.
AB  - The outcome of adult acute lymphoblastic leukemia (ALL) has substantially
      improved by adopting pediatric-inspired regimens, and approximately half of the
      patients are nowadays cured. The evaluation of minimal residual disease currently
      represents the most important prognostic indicator, which drives treatment
      algorithms, which include allogeneic stem cell transplantation (allo-SCT)
      allocation. Indeed, for high-risk patients, allo-SCT should be pursued as soon as
      possible, whereas in standard-risk patients this procedure should be avoided also
      in light of related toxicity and because there are no significant benefits.
      Furthermore, better characterization of the molecular genetic events can drive
      therapeutic decisions: a historical example in this respect is represented by the
      use of tyrosine kinase inhibitors (TKIs) in Philadelphia chromosome-positive ALL;
      in the upcoming future, TKIs might be used also in other subgroups, such as
      breakpoint cluster region/Abelson 1-like cases and others with deregulated
      tyrosine kinases. Finally, the greatest progress is currently achieved with new
      immunotherapies targeting frequently expressed surface antigens in ALL. It is
      also a new chance for elderly ALL patients, so far spared from intensive
      chemotherapy and allo-SCT. These targeted therapies will substantially change
      this treatment algorithm and the great challenge is to find optimal sequence of
      the extended therapy options in an individual patient.

PMID- 29653824
TI  - Health and safety management system to improve the self-protection plans in
      intensive care units.

PMID- 29653825
TI  - Re: Association between fish consumption, dietary omega-3 fatty acids and
      persistent organic pollutants intake, and type 2 diabetes in 18 First Nations in
      Ontario, Canada.

PMID- 29653826
TI  - The surgery and repeat aspiration outcomes of the atypia of undetermined
      significance/follicular lesion of undetermined significance category in The
      Bethesda System for Reporting Thyroid Cytopathology.
AB  - BACKGROUND/OBJECTIVE: The atypia of undetermined significance/follicular lesion
      of undetermined significance (AUS/FLUS) category is one of six diagnostic
      categories of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC).
      In this study, we report the diagnostic distribution of thyroid fine needle
      aspiration (FNA) cytology and analyze the outcome of AUS/FLUS cases. METHODS: A
      total of 29,937 thyroid FNA results, reported between April 2012 and December
      2016, were retrieved from the database of a medical center. We reviewed the
      electronic medical records and analyzed the management of these patients.
      RESULTS: Overall frequency of AUS/FLUS is 3.1% in our laboratory, which is at the
      lower limit of the recommended range. Of these, 891 reports of AUS/FLUS from 770
      patients were identified. Out of the 770 patients, 367 had surgical intervention.
      In these 367 patients, final surgical pathology yielded 204 (55.6%) malignancies,
      12 indeterminateness (3.3%), and 151 (41.1%) benignity. Among these surgical
      patients, 113 (30.8%) had received a repeat FNA of the thyroid before thyroid
      resection. The difference between the malignancy rates among patients who
      directly received surgery after the first AUS/FLUS diagnosis (132 of 254, 52.0%)
      and patients having a repeat FNA before surgery (72 of 113, 63.7%) was not
      statistically significant. CONCLUSION: Our results are in agreement with AUS/FLUS
      diagnoses in less than 7% of specimens, and confirm that it is appropriate to
      perform either a repeat thyroid FNA or thyroid lobectomy, with the clinical
      decision being subject to the standardized management protocols of the second
      edition of TBSRTC in the AUS/FLUS category.

PMID- 29653827
TI  - Dwarf chickens with low monocytes/macrophages phagocytic activity show low
      antibody titers but greater performance.
AB  - Monocytes/macrophages phagocytosis has key roles in inflammatory responses.
      However, systematic research on the effects of monocytes/macrophages phagocytosis
      on production and reproductive performance in dwarf chickens is lacking. In this
      study, we developed the HCT-8-MTT method to detect monocytes/macrophages
      phagocytosis product (PP) which was accuracy, flexible, and saving time. Based on
      PP in 990 dwarf chickens (890 hens and 100 cocks), chickens were divided into
      high phagocytosis product group (HPPG) and low phagocytosis product group (LPPG).
      In production performance, chickens in LPPG have higher laying rate at 24 wk and
      71 wk and higher average egg weight at 23 wk and 24 wk than in HPPG (P < 0.05).
      The levels of follicle-stimulating hormone and luteinizing hormone were higher in
      LPPG than in HPPG at 58 wk (P < 0.01). In the reproductive performance, the
      fertilization rate in LPPG was higher than that in HPPG at 45 wk, 49 wk, and 53
      wk (P < 0.05). Chickens in LPPG have higher hatchability than HPPG at 45 wk and
      49 wk (P < 0.05). In LPPG, the mRNA expression levels of follicle-stimulating
      hormone receptor and CD9 in the follicle were higher than HPPG (P < 0.05). In the
      immune response, chickens with higher PP levels showed higher antibody titers for
      the avian influenza virus H9 inactivated vaccine (P < 0.01). Therefore,
      monocytes/macrophages PP was positively associated with antibody titers and
      negatively related to production and reproductive performance, and these findings
      have practical applications for the optimization of production in the poultry
      industry.

PMID- 29653828
TI  - Ostrich specific semen diluent and sperm motility characteristics during in vitro
      storage.
AB  - The dilution of semen is a very important initial process for semen processing
      and evaluation, storage and preservation in vitro and efficient artificial
      insemination. The aim of the study was to evaluate the effect of two synthetic
      diluents (OS1 and OS2) on ostrich sperm motility parameters during in vitro
      storage. Formulation of OS1 was based on macro minerals (Na, K, P, Ca, Mg) and
      OS2 on the further addition of micro minerals (Se and Zn), based on mineral
      concentration determined in the ostrich seminal plasma (SP). Sperm motility was
      evaluated at different processing stages (neat, after dilution, during storage
      and after storage) by measuring several sperm motility variables using the Sperm
      Class Analyzer(r) (SCA). Processing (dilution, cooling and storage) of semen for
      in vitro storage purposes decreased the values for all sperm motility variables
      measured. The percentage motile (MOT) and progressive motile (PMOT) sperm
      decreased 20% to 30% during 24 h of storage, independent of diluent type. Quality
      of sperm swim (LIN, STR and WOB), however, was sustained during the longer
      storage periods (48 h) with the OS2 diluent modified with Se and Zn additions.
      Quality of sperm swim with use of OS1 was 6% to 8% less for the LIN, STR, and WOB
      variables. Male fitted as a fixed effect accounted for >60% of the variation for
      certain sperm motility variables (PMOT, MOT, VCL, VSL, VAP and ALH) evaluated at
      different processing stages. Semen from specific males had sustained sperm
      motility characteristics to a greater extent than that of other males during the
      24-h storage period.

PMID- 29653829
TI  - Mineral profiling of ostrich (Struthio camelus) seminal plasma and its
      relationship with semen traits and collection day.
AB  - Successful assisted reproduction techniques, with specific focus on in vitro
      semen storage for artificial insemination, are dependent on certain key elements
      which includes the biochemical profiling of semen. The objective of this study
      was to complete an ostrich seminal plasma (SP) evaluation by inductively coupled
      plasma mass spectrometry (ICP-MS) among seven males at different daily intervals
      (day 1, 3, 7, 11, 15, 19, 21, 23, 25, 26, 27, 28) for a period of 28 days during
      spring (August to September) for mineral profiling. The effect of collection day
      and male on sperm concentration, semen volume and seminal plasma volume, was
      explored as well as the relationships amongst these specific sperm traits and SP
      minerals. Variation amongst SP mineral concentrations, accounted for by the fixed
      effects of sperm concentration, semen volume, seminal plasma volume, collection
      day and male, ranged from 18% to 77%. Male had the largest effect on variation in
      SP minerals, namely: phosphorus (P), potassium (K), calcium (Ca), sodium (Na),
      boron (B), iron (Fe), cobalt (Co), nickel (Ni), copper (Cu), molybdenum (Mo),
      barium (Ba), arsenic (As) and selenium (Se). Sperm concentration instigated
      fluctuations of P, magnesium (Mg), B, zinc (Zn), Fe, aluminium (Al), Se,
      manganese (Mn) and lead (Pb). Semen volume had an effect on Na, K, B, Pb and Ba
      while seminal plasma volume only influenced variation in Na. There were
      fluctuations among collection days of specific micro minerals, Ni and Mo, with
      initial Ni concentrations being relatively greater and Mo at lesser
      concentrations. Semen volume, seminal plasma volume and sperm concentration
      varied amongst males. Sperm concentrations during the initial collection days, 1
      and 3, were less than that for days 7 to 28. Significant variation of SP minerals
      and sperm characteristics among ejaculates and males suggest an association of
      these specific elements with sperm function and are, therefore, considered to be
      of potential importance to success of assisted reproduction technology for the
      ostrich. The relationship amongst sperm concentration and collection day confirms
      the need to conduct an initial period of collection to stabilise a greater sperm
      concentration to optimise sperm numbers for artificial insemination purposes.

PMID- 29653830
TI  - Jean-Martin Charcot and Parkinson's disease: Teaching and teaching materials.
AB  - James Parkinson's 1817 seminal article was not well known in France until 1861,
      when Jean-Martin Charcot and his friend, Alfred Vulpian, published a detailed
      description in French of paralysis agitans. Their article provided clinical
      information to help French physicians make an accurate diagnosis by considering
      gait, shaking and rigidity as well as masked facies. As Charcot always had a
      strong desire to teach, this article describes his lessons on Parkinson's disease
      from 1868 to 1888, and also examines the teaching approach he used to pass on his
      latest findings to his students and colleagues. Charcot also used his role as
      thesis advisor to disseminate Parkinson's work, and seven of the theses he
      oversaw, which until now have been overlooked, reveal another facet of his
      teacher-student relationship. These dissertations provided Charcot with an
      opportunity to highlight what he had already identified concerning what is today
      referred to as 'Parkinson-plus syndromes'. Finally, this report concludes with an
      historical survey of the teaching materials that Paul Richer and Albert Londe
      developed for the Master at La Salpetriere to provide him with visual
      documentation.

PMID- 29653831
TI  - Does the Movement Assessment Battery for Children-2 at 3 years of age predict
      developmental coordination disorder at 4.5 years of age in children born very
      preterm?
AB  - BACKGROUND: Very preterm children (VPT) are at high risk for developmental
      coordination disorder (DCD). The Movement Assessment Battery for Children-2 (MABC
      2) Test is commonly used to identify children with DCD, but little is known about
      the predictive validity of this assessment in this population. AIMS: The aims of
      this study were to determine if MABC-2 scores at 3 years can predict DCD at 4.5
      years and if DCD can be reliably identified in VPT children at 3 years. METHODS
      AND PROCEDURES: In a retrospective sample of 165 VPT children, logistic
      regression was used to determine if the MABC-2 score at 3 years is predictive of
      DCD at 4.5 years. Cross-tabulations were used to determine the relationship
      between scores at 3 years and DCD at 4.5 years. OUTCOMES AND RESULTS: MABC-2
      scores at age 3 were a significant predictor (OR = 0.82, p = 0.001) of DCD
      diagnosis at 4.5 years. The MABC-2 has excellent sensitivity (90%), moderate
      specificity (69%), small to moderate positive predictive value (38%) and high
      negative predictive value (97%). CONCLUSIONS AND IMPLICATIONS: The MABC-2 is
      highly sensitive in identifying VPT children with DCD, but also has many false
      positives. MABC-2 scores can reliably predict VPT children who are not at risk of
      DCD.

PMID- 29653832
TI  - Screening of ligands for redox-active europium using magnetic resonance imaging.
AB  - We report a screening procedure to predict ligand coordination to EuII and EuIII
      using magnetic resonance imaging in which bright images indicate complexation and
      dark images indicate no complexation. Here, paramagnetic GdIII is used as a
      surrogate for EuIII in the screening procedure to enable detection with magnetic
      resonance imaging. The screening procedure was tested using a set of eight
      ligands with known coordination to EuII and EuIII, and results were found to be
      consistent with expected binding. Validation of the screening procedure with
      known coordination chemistry enables use with new ligands in the future.

PMID- 29653833
TI  - Validation by Cardiac Catheterization of Noninvasive Estimation of Time Constant
      of Left Ventricular Pressure Decline as an Index of Relaxation by Speckle
      Tracking Echocardiography.
AB  - There has been no established echocardiographic parameter to accurately assess
      left ventricular (LV) relaxation. Impaired LV relaxation assessed by the time
      constant of LV pressure decline (Tau) is one of the major components of diastolic
      dysfunction. We sought to noninvasively estimate Tau (eTau) by speckle tracking
      echocardiography (STE) and to validate the eTau against Tau by catheterization.
      Tau was reported to be calculated using the isovolumic relaxation time (IVRT), LV
      end-systolic pressure, and left atrial (LA) pressure. We reported that pulmonary
      capillary wedge pressure (ePCWP) can be noninvasively and accurately estimated as
      10.8 - 12.4 * Log (LA active emptying function/minimum LA volume index).
      Therefore, the eTau by STE is noninvasively calculated using the formula: eTau =
      IVRT / (ln 0.9 * systolic blood pressure-ln ePCWP). Echocardiographic parameters
      were measured just before catheterization in 110 patients with cardiac disease
      (age 72 +/- 8). There was a good correlation between the eTau and Tau by
      catheterization (r = 0.69, p <0.001), whereas IVRT and the e' had a poor
      correlation with Tau (r = 0.33 and -0.33, respectively). The sensitivity and
      specificity of the eTau to predict prolonged Tau (>48 ms) was 77% and 91%,
      respectively, with area under curve of 0.87 using an optimal cutoff of 48 ms.
      Bland-Altman analysis revealed a good agreement between the eTau and Tau. In
      conclusion, this study demonstrated that the eTau by our noninvasive method has a
      good correlation with Tau obtained by cardiac catheterization. LV relaxation may
      be noninvasively and accurately estimated by STE.

PMID- 29653834
TI  - Intracellular Receptor Modulation: Novel Approach to Target GPCRs.
AB  - Recent crystal structures of multiple G protein-coupled receptors (GPCRs) have
      revealed a highly conserved intracellular pocket that can be used to modulate
      these receptors from the inside. This novel intracellular site partially overlaps
      with the G protein and beta-arrestin binding site, providing a new manner of
      pharmacological intervention. Here we provide an update of the architecture and
      function of the intracellular region of GPCRs, until now portrayed as the
      signaling domain. We review the available evidence on the presence of
      intracellular binding sites among chemokine receptors and other class A GPCRs, as
      well as different strategies to target it, including small molecules, pepducins,
      and nanobodies. Finally, the potential advantages of intracellular (allosteric)
      ligands over orthosteric ligands are also discussed.

PMID- 29653835
TI  - Positron Emission Tomography Studies of the Glial Cell Marker Translocator
      Protein in Patients With Psychosis: A Meta-analysis Using Individual Participant
      Data.
AB  - BACKGROUND: Accumulating evidence suggests that the immune system may be an
      important target for new treatment approaches in schizophrenia. Positron emission
      tomography and radioligands binding to the translocator protein (TSPO), which is
      expressed in glial cells in the brain including immune cells, represents a
      potential method for patient stratification and treatment monitoring. This study
      examined whether patients with first-episode psychosis and schizophrenia had
      altered TSPO levels compared with healthy control subjects. METHODS: PubMed was
      searched for studies comparing patients with psychosis with healthy control
      subjects using second-generation TSPO radioligands. The outcome measure was total
      distribution volume (VT), an index of TSPO levels, in frontal cortex, temporal
      cortex, and hippocampus. Bayes factors (BFs) were applied to examine the relative
      support for higher, lower, or no difference in patients' TSPO levels compared
      with healthy control subjects. RESULTS: Five studies, with 75 participants with
      first-episode psychosis or schizophrenia and 77 healthy control subjects, were
      included. BFs showed strong support for lower VT in patients relative to no
      difference (all BFs > 32), or relative to higher VT (all BFs > 422), in all brain
      regions. From the posterior distributions, mean patient-control differences in
      standardized VT values were -0.48 for frontal cortex (95% credible interval
      [CredInt] = -0.88 to 0.09), -0.47 for temporal cortex (CredInt = -0.87 to -0.07),
      and -0.63 for hippocampus (CredInt = -1.00 to -0.25). CONCLUSIONS: The lower
      levels of TSPO observed in patients may correspond to altered function or lower
      density of brain immune cells. Future studies should focus on investigating the
      underlying biological mechanisms and their relevance for treatment.

PMID- 29653836
TI  - Port Baseline Biological Surveys and seaweed bioinvasions in port areas: What's
      the matter in the Adriatic Sea?
AB  - One of the objectives of the BALMAS project was to conduct Port Baseline
      Biological Surveys of native and non-indigenous benthic flora in 12 Adriatic
      ports. Samples of macroalgae growing on vertical artificial substrates were
      collected in spring and autumn 2014 and/or 2015. A total number of 248 taxa, 152
      Rhodophyta, 62 Chlorophyta, and 34 Ochrophyta, were identified. Of these, 13 were
      non-indigenous seaweeds, mainly filamentous macroalgae, that were probably
      introduced through hull fouling. Some of these taxa had already been described in
      the study areas, others were recorded for the first time, a few were no longer
      detected at sites where they had previously been recorded (e.g. Sargassum
      muticum). Some other NISS reported for the Adriatic Sea, were not collected at
      any sampling site (i.e. Caulerpa cylindracea, Codium fragile). Possible reasons
      for the absence of these species are discussed.

PMID- 29653837
TI  - The Relation between alpha-Helical Conformation and Amyloidogenicity.
AB  - Amyloid fibrils are stable aggregates of misfolded proteins and polypeptides that
      are insoluble and resistant to protease activity. Abnormal formation of amyloid
      fibrils in vivo may lead to neurodegenerative disorders and other systemic
      amyloidosis, such as Alzheimer's, Parkinson's, and atherosclerosis. Because of
      their clinical importance, amyloids are under intense scientific research. It is
      believed that short polypeptide segments within proteins are responsible for the
      transformation of correctly folded proteins into parts of larger amyloid fibrils
      and that this transition is modulated by environmental factors, such as pH, salt
      concentration, interaction with the cell membrane, and interaction with metal
      ions. Most studies on amyloids focus on the amyloidogenic sequences. The focus of
      this study is on the structure of the amyloidogenic alpha-helical segments
      because the alpha-helical secondary structure has been recognized to be a key
      player in different stages of the amyloidogenesis process. We have previously
      shown that the alpha-helical conformation may be expressed by two parameters
      (theta and rho) that form orthogonal coordinates based on the Ramachandran
      dihedrals (phi and psi) and provide an illuminating interpretation of the alpha
      helical conformation. By performing statistical analysis on alpha-helical
      conformations found in the Protein Data Bank, an apparent relation between alpha
      helical conformation, as expressed by theta and rho, and amyloidogenicity is
      revealed. Remarkably, random amino acid sequences, whose helical structures were
      obtained from the most probable dihedral angles, revealed the same dependency of
      amyloidogenicity, suggesting the importance of alpha-helical structure as opposed
      to sequence.

PMID- 29653839
TI  - Significance of Anti-Myosin Antibody Formation in Patients With Myocardial
      Infarction: A Prospective Observational Study.
AB  - BACKGROUND: Anti-myosin antibodies (AMAs) are often formed in response to
      myocardial infarction (MI) and have been implicated in maladaptive cardiac
      remodelling. We aimed to: (1) compare AMA formation in patients with Non-ST
      Elevation MI (NSTEMI) and ST-Elevation MI (STEMI); (2) evaluate factors
      predicting autoantibody formation; and, (3) explore their functional
      significance. METHODS: Immunoglobulin M (IgM) and Immunoglobulin G (IgG) AMA
      titres were determined in serum samples collected at admission, 3 and 6 months
      post MI. The relationship between demographic and clinical data, and antibody
      formation, was investigated to determine factors predicting antibody formation
      and functional significance. RESULTS: Forty-three patients were consecutively
      recruited; 74.4% were positive for IgM at admission, compared with 23.3% for IgG.
      Mean IgG levels increased by 1.24% (+/-0.28) at 3 months, and 13.55% (+/-0.13) at
      6 months post MI. Mean antibody levels were significantly higher in the NSTEMI
      cohort at both follow-up time points for IgG (p<0.001, p<0.0001), but not IgM
      (p=0.910, p=0.066). A moderately positive correlation between infarct size and
      increase in mean IgM concentration was observed at 3 months (r(98)=0.455;
      p=0.015). Anti-myosin antibody formation was not associated with an unfavourable
      outcome at follow-up. CONCLUSIONS: Anti-myosin antibodies are formed in a
      significant proportion of patients following MI, particularly among those with
      NSTEMI. While IgM levels fall after infarction, IgG levels increase and persist
      beyond 6 months of follow-up. This raises the possibility that they may
      contribute to long-term myocardial damage and dysfunction. Future research should
      focus on the specific epitopes that are targeted by these antibodies, and their
      functional significance. This may result in the emergence of novel therapies to
      attenuate cardiac dysfunction in MI patients.

PMID- 29653838
TI  - A Multicolor Split-Fluorescent Protein Approach to Visualize Listeria Protein
      Secretion in Infection.
AB  - Listeria monocytogenes is an intracellular food-borne pathogen that has evolved
      to enter mammalian host cells, survive within them, spread from cell to cell, and
      disseminate throughout the body. A series of secreted virulence proteins from
      Listeria are responsible for manipulation of host-cell defense mechanisms and
      adaptation to the intracellular lifestyle. Identifying when and where these
      virulence proteins are located in live cells over the course of Listeria
      infection can provide valuable information on the roles these proteins play in
      defining the host-pathogen interface. These dynamics and protein levels may vary
      from cell to cell, as bacterial infection is a heterogeneous process both
      temporally and spatially. No assay to visualize virulence proteins over time in
      infection with Listeria or other Gram-positive bacteria has been developed.
      Therefore, we adapted a live, long-term tagging system to visualize a model
      Listeria protein by fluorescence microscopy on a single-cell level in infection.
      This system leverages split-fluorescent proteins, in which the last strand of a
      fluorescent protein (a 16-amino-acid peptide) is genetically fused to the
      virulence protein of interest. The remainder of the fluorescent protein is
      produced in the mammalian host cell. Both individual components are
      nonfluorescent and will bind together and reconstitute fluorescence upon
      virulence-protein secretion into the host cell. We demonstrate accumulation and
      distribution within the host cell of the model virulence protein InlC in
      infection over time. A modular expression platform for InlC visualization was
      developed. We visualized InlC by tagging it with red and green split-fluorescent
      proteins and compared usage of a strong constitutive promoter versus the
      endogenous promoter for InlC production. This split-fluorescent protein approach
      is versatile and may be used to investigate other Listeria virulence proteins for
      unique mechanistic insights in infection progression.

PMID- 29653840
TI  - Entrustable Professional Activities (EPAs) for Simulation Leaders: The Time Has
      Come.

PMID- 29653841
TI  - Medical Students Teaching Medical Students Surgical Skills: The Benefits of Peer
      Assisted Learning.
AB  - OBJECTIVE: Teaching surgical skills is a labor intensive process, requiring a
      high tutor to student ratio for optimal success, and teaching for undergraduate
      students by consultant surgeons is not always feasible. A surgical skills course
      was developed, with the aim of assessing the effectiveness of undergraduate
      surgical peer-assisted learning. DESIGN: Five surgical skills courses were
      conducted looking at eight domains in surgery, led by foundation year doctors and
      senior medical students, with a tutor to student ratio of 1:4. Precourse and
      postcourse questionnaires (Likert scales 0-10) were completed. Mean scores were
      compared precourse and postcourse. SETTING: Surgical skills courses took place
      within clinical skills rooms in the Queen Elizabeth Hospital Birmingham (UK).
      PARTICIPANTS: Seventy students (59 medical, 2 dental, and 9 physician associate
      students) from a range of academic institutions across the UK completed the
      course. RESULTS: There was an overall increase in mean scores across all eight
      domains. Mean improvement score precourse and postcourse in WHO surgical safety
      checklist (+3.94), scrubbing (+2.99), gowning/gloving (+3.34), knot tying
      (+5.53), interrupted sutures (+5.89), continuous sutures (+6.53), vertical
      mattress sutures (+6.46), and local anesthesia (+3.73). CONCLUSIONS: Peer
      assisted learning is an effective and feasible method for teaching surgical
      skills in a controlled environment, subsequently improving confidence among
      healthcare undergraduates. Such teaching may provide the basis for feasibly mass
      producing surgical skills courses for healthcare students.

PMID- 29653842
TI  - Hearing loss in older adults - From epidemiological insights to national
      initiatives.
AB  - The broader implications of hearing loss for the health and functioning of older
      adults have begun to be demonstrated in epidemiologic studies. These research
      findings on the association between hearing loss and poorer health outcomes have
      formed the foundation for national initiatives on hearing loss and public health.
      These national initiatives range from the Aging and Cognitive Health Evaluation
      in Elders (ACHIEVE) clinical trial to the recent passage of the bipartisan Over
      The-Counter Hearing Aid Act. Utilizing population health research methodologies
      to study hearing loss can provide the foundation for initiating top-down
      approaches to increase the adoption and accessibility of hearing care for older
      Americans with hearing loss.

PMID- 29653844
TI  - Alfonso de la Pena Pineda and the Urology exchange by correspondence.
AB  - INTRODUCTION: In 1943, the brothers Alfonso and Emilio de la Pena Pineda proposed
      creating a communication system by correspondence as in North America, an idea
      welcomed by Spanish urologists, a system that was named the Urology Exchange by
      Correspondence. MATERIAL AND METHODS: A thorough reading and detailed analysis
      was conducted of content from 1944 to 1953, with an average of 3 pages of folio
      size of each copy. RESULT: A total of 105 issues containing 234 urological
      presentations were sent, signed by 67 Spanish urologists, 2 Portuguese urologists
      and 1 general surgeon. Thirty-nine of these presentations were translations of a
      similar U.S. publication. The subject matter corresponded to curious or rare
      personal cases, concerning conditions or problems of the most common urological
      diseases in that era, of which only 20 of those articles stand out. In general,
      the content is of little use and interest, which prompted the gradual decline in
      the collaboration until it disappeared. CONCLUSION: The proposal was answered
      mostly by those who had a professional relationship with the chair of Urology of
      the Faculty of Medicine of Madrid directed by Alfonso de la Pena. The subject
      matter of the personal case studies, most of which lacked importance, lead to the
      gradual decline in the contribution of presentations until its eventual end. Only
      a few articles stand out. The study's major value consists of collecting and
      analysing the content of what is highly likely the only complete collection in
      existence, given that it was not edited for printing and was distributed only as
      correspondence and cannot therefore be found in public libraries.

PMID- 29653843
TI  - Neer Award 2018: Platelet-derived growth factor receptor alpha co-expression
      typifies a subset of platelet-derived growth factor receptor beta-positive
      progenitor cells that contribute to fatty degeneration and fibrosis of the murine
      rotator cuff.
AB  - BACKGROUND AND HYPOTHESIS: After massive tears, rotator cuff muscle often
      undergoes atrophy, fibrosis, and fatty degeneration. These changes can lead to
      high surgical failure rates and poor patient outcomes. The identity of the
      progenitor cells involved in these processes has not been fully elucidated.
      Platelet-derived growth factor receptor beta (PDGFRbeta) and platelet-derived
      growth factor receptor alpha (PDGFRalpha) have previously been recognized as
      markers of cells involved in muscle fibroadipogenesis. We hypothesized that
      PDGFRalpha expression identifies a fibroadipogenic subset of PDGFRbeta+
      progenitor cells that contribute to fibroadipogenesis of the rotator cuff.
      METHODS: We created massive rotator cuff tears in a transgenic strain of mice
      that allows PDGFRbeta+ cells to be tracked via green fluorescent protein (GFP)
      fluorescence. We then harvested rotator cuff muscle tissues at multiple time
      points postoperatively and analyzed them for the presence and localization of
      GFP+ PDGFRbeta+ PDGFRalpha+ cells. We cultured, induced, and treated these cells
      with the molecular inhibitor CWHM-12 to assess fibrosis inhibition. RESULTS: GFP+
      PDGFRbeta+ PDGFRalpha+ cells were present in rotator cuff muscle tissue and,
      after massive tears, localized to fibrotic and adipogenic tissues. The frequency
      of PDGFRbeta+ PDGFRalpha+ cells increased at 5 days after massive cuff tears and
      decreased to basal levels within 2 weeks. PDGFRbeta+ PDGFRalpha+ cells were
      highly adipogenic and significantly more fibrogenic than PDGFRbeta+ PDGFRalpha-
      cells in vitro and localized to adipogenic and fibrotic tissues in vivo.
      Treatment with CWHM-12 significantly decreased fibrogenesis from PDGFRbeta+
      PDGFRalpha+ cells. CONCLUSION: PDGFRbeta+ PDGFRalpha+ cells directly contribute
      to fibrosis and fatty degeneration after massive rotator cuff tears in the mouse
      model. In addition, CWHM-12 treatment inhibits fibrogenesis from PDGFRbeta+
      PDGFRalpha+ cells in vitro. Clinically, perioperative PDGFRbeta+ PDGFRalpha+ cell
      inhibition may limit rotator cuff tissue degeneration and, ultimately, improve
      surgical outcomes for massive rotator cuff tears.

PMID- 29653845
TI  - Inhibition of caspase-1 prolongs survival of mice infected with rabies virus.
AB  - Rabies virus infects almost all mammals resulting in lethal disease. To date
      there is no treatment available for symptomatic rabies and there is an urgent
      need to develop treatment strategies that would prolong survival, thereby
      providing a window of opportunity for the host to mount a protective immune
      response. We hypothesized that both virus and excessive immune response
      contribute to disease and that interfering with both is necessary to prevent
      lethal disease. Here, we have inhibited the pro-inflammatory response associated
      with pyroptosis and showed that inhibition of CASP-1 had a beneficial effect on
      survival time. Our results confirm that some inflammatory responses may be
      involved in the pathogenesis of severe disease and the results suggest that
      effective intervention includes inhibition of virus and host response.

PMID- 29653846
TI  - "When you are injected, the baby is protected:" Assessing the acceptability of a
      maternal Tdap vaccine based on mothers' knowledge, attitudes, and beliefs of
      pertussis and vaccinations in Lusaka, Zambia.
AB  - INTRODUCTION: Severe and fatal pertussis infections are concentrated among
      infants who are too young to be protected through routine vaccinations. Maternal
      Tdap (mTdap), which is now the standard of care in the US and UK, is considered
      to be the most effective way to address this gap in preventative care. Little is
      known about how pregnant women in low-resource settings might view mTdap. To
      inform strategies for mTdap implementation in these contexts, public health
      researchers sought to understand knowledge, attitudes, and beliefs toward
      pertussis and maternal vaccines and assess the barriers to vaccine acceptance.
      METHODS: We conducted focus group discussions (FGDs) among mothers who
      participated in a longitudinal birth cohort study at the Chawama primary health
      center in Lusaka, Zambia. Since SAMIPS was not a clinical trial, but instead an
      observational cohort study, registration on clinicaltrials.gov was not required.
      Trained interviewers conducted the FGDs in January 2016 using a semi-structured
      interview guide, exploring participants' knowledge, attitudes and beliefs toward
      pertussis and vaccines. We analyzed the transcripts using Nvivo v.11 software.
      RESULTS: Fifty mothers participated across 7 FGDs. Mothers had limited knowledge
      of pertussis and vaccines, yet expressed generally positive views of vaccinating
      themselves and their children. Participants conveyed very little vaccine
      hesitancy around maternal vaccinations, and discussed how they could protect
      their children's health. Mothers also highlighted barriers and facilitators to
      vaccine uptake, which included partner involvement, feelings of maternal
      authority over healthcare decision-making, and community rumors about Western
      medicine. CONCLUSION: Mothers viewed vaccinations as an important method to keep
      their children healthy, despite cultural myths and misconceptions about pertussis
      and vaccines. FGD results suggest that vaccine acceptability is high in Zambia,
      which is a critical factor to vaccine uptake. A strategy addressing myths and
      misconceptions should be prioritized if and when mTdap is introduced across low
      resource settings.

PMID- 29653848
TI  - Inactivated infectious bronchitis virus vaccine encapsulated in chitosan
      nanoparticles induces mucosal immune responses and effective protection against
      challenge.
AB  - Avian infectious bronchitis virus (IBV) is one of the most important viral
      diseases of poultry. The mucosa of upper respiratory tract, specially the
      trachea, is the primary replication site for this virus. However, conventional
      inactivate IBV vaccines usually elicit reduced mucosal immune responses and local
      protection. Thus, an inactivated IBV vaccine containing BR-I genotype strain
      encapsulated in chitosan nanoparticles (IBV-CS) was produced by ionic gelation
      method to be administered by oculo-nasal route to chickens. IBV-CS vaccine
      administered alone resulted in markedly mucosal immune responses, characterized
      by high levels of anti-IBV IgA isotype antibodies and IFNgamma gene expression at
      1dpi. The association of live attenuated Massachusetts IBV and IBV-CS vaccine
      also induced strong mucosal immune responses, though a switch from IgA isotype to
      IgG was observed, and IFNgamma gene expression peak was late (at 5 dpi). Efficacy
      of IBV-CS was evaluated by tracheal ciliostasis analysis, histopathology
      examination, and viral load determination in the trachea and kidney. The results
      indicated that IBV-CS vaccine administered alone or associated with a live
      attenuated heterologous vaccine induced both humoral and cell-mediated immune
      responses at the primary site of viral replication, and provided an effective
      protection against IBV infection at local (trachea) and systemic (kidney) sites.

PMID- 29653847
TI  - Local thermal reaction after influenza vaccination: Quantification by infrared
      imaging and biometric considerations.
AB  - BACKGROUND: Extensive clinical investigations are mandatory to evaluate the
      safety and reactogenicity of vaccines. The recording of common adverse events
      like injection site soreness or general discomfort derives from individual
      subjective perceptions. Thermal imaging at the injection site possibly provides a
      non-subjective and a non-invasive approach to supplement this evaluation.
      RESULTS: A protocol for quantified injection-site infrared imaging included 86
      participants during a flu vaccine campaign, 40% of whom had a thermal reaction of
      1  degrees C; 25-30% had no thermal response. There was little subjective pain
      reporting and no clinical correlations were observed except with post-vaccination
      erythema. Higher responses were linked with advanced age and multiple previous
      vaccinations. CONCLUSION: Evan if influenza vaccine was only moderately
      reactogenic, a thermal response was detectable in about 70% of vaccinees, though
      no relationship to reactogenicity was seen. Infrared imaging might however be a
      prospective tool for individual studies of vaccine-induced vascular responses.

PMID- 29653849
TI  - Direct-to-adolescent text messaging for vaccine reminders: What will parents
      permit?
AB  - BACKGROUND: Direct-to-adolescent text messaging may be a consideration for
      vaccine reminders, including human papilloma virus (HPV), but no studies have
      explored the minimum age at which parents would allow adolescents to receive a
      text message. METHODS: We distributed a survey to parents of 10-17 year olds
      during any office visit in two practice based research networks in South Carolina
      and Oklahoma. We asked about parental preference for receiving vaccine reminders
      for their adolescent, whether they would allow the healthcare provider to
      directly message their adolescent, and if so, what would be the acceptable
      minimum age. RESULTS: In 546 surveys from 11 practices, parents of females were
      more supportive of direct-to-teen text message reminders than were parents of
      males, (75% v. 60%, p < .001). The median age at which parents would allow direct
      text messages from physicians' offices was 14 in females compared to 15 in males,
      p = .049. We found a correlation between the child's age and the youngest age at
      which parents would allow a direct text message. Of the parents who permitted a
      text message directly to their adolescent, most reported an allowable age higher
      than their adolescent's current age until the age of 15. CONCLUSION: Our study
      suggests that direct-to-adolescent text messaging would be allowed by parents for
      older adolescents. This supports an intervention aimed at older adolescents, such
      as for receipt of MCV4 dose #2, delayed HPV vaccine series completion and annual
      influenza vaccination.

PMID- 29653850
TI  - Mumps disease in Beijing in the era of two-dose vaccination policy, 2005-2016.
AB  - BACKGROUND: Since the introduction of mumps-containing vaccines (MuCV) in 1995 in
      Beijing, two-dose MuCV vaccination policy has been used, with the 1st and 2nd
      doses given at 18 months and 6 years of age, respectively. METHODS: Mumps
      epidemiology during 2005-2016 was described using surveillance data. Vaccine
      effectiveness (VE) of MuCV against disease was estimated for cases born during
      2002-2009 and reported in 2016. VE against complications was estimated for all
      cases. MuCV coverage was estimated for children born during 1999-2015 using data
      from Beijing Immunization Information System. RESULTS: Overall mumps incidence
      decreased from 30.38/100,000 persons in 2005 to 10.26/100,000 persons in 2016.
      Incidence declines in children aged <15 years. No significant incidence change
      occurred in adults aged >=20 years. Incidence in persons aged 15-19 years
      increased by 132.73% in 2012 when compared with in 2005. Rates of
      meningitis/encephalitis, orchitis, and other complications among cases decreased
      during 2005-2016. The majority (97%) of outbreaks occurred in schools. Total
      number of outbreaks and average outbreak size decreased during 2005-2016. Among
      outbreak-related cases, 69.54%, 29.67% and 0.79% had received 0 dose, 1dose and 2
      doses of MuCV, respectively. Coverage of the 1st MuCV dose at 2-5 years of age
      increased by 42.75% during 2005-2016. Coverage of the 2nd MuCV dose at 6-14 years
      of age increased by 12.87% during 2013-2016. Overall VE estimates of MuCV against
      mumps disease were 74.51% (95% CI: 65.57-81.34%) for 1 dose and 83.16% (95% CI:
      78.60-86.31%) for 2 doses. Both VE estimates increased by birth cohorts. VE
      estimate against complications for 2-dose MuCV was higher than for 1 dose.
      CONCLUSIONS: Increasing MuCV coverage achieved declining mumps incidence and
      complication rate. Current epidemiology supported 2-dose MuCV vaccination policy.
      The incidence rise in persons aged 15-19 years in 2012 and waning immunity for
      the 2nd MuCV dose merited close follow-up.

PMID- 29653851
TI  - [Iso Kikuchi syndrome: Congenital onychodysplasia of the index fingers, or COIF
      syndrome].

PMID- 29653852
TI  - [Cutaneous localization of Rosai-Dorfman Disease].

PMID- 29653853
TI  - [Alopecia areata under ipilimumab].

PMID- 29653854
TI  - Esophagectomy in patients with liver cirrhosis: a systematic review and Bayesian
      meta-analysis.
AB  - INTRODUCTION: Patients with esophageal carcinoma and concomitant liver cirrhosis
      carry a high operative risk and may be denied esophagectomy. We performed a
      systematic review of the literature and meta-analysis to investigate
      postoperative outcomes in these patients. METHODS: Studies reporting outcomes
      after esophagectomy in patients with liver cirrhosis were searched in Medline,
      Embase, Cochrane Library, ISI Web of Science, and Scopus until June 2017,
      matching the terms "liver cirrhosis", "esophageal neoplasm" and/or "esophageal
      surgery". Extracted data included study characteristics, demographic and clinical
      patient characteristics, type of surgical procedure, and postoperative outcomes.
      A systematic review and Bayesian meta-analysis were performed. RESULTS: Five
      observational, retrospective and single-arm studies with a total of 157 patients
      were included. The main cause of death was liver failure followed by
      pneumonia/sepsis and anastomotic leak. Ascites and pleural effusion were the most
      frequent postoperative complications (pooled rates 36% and 34%, respectively).
      The pooled morbidity rate was 74% (95% HPD=46-81%) while the pooled mortality was
      18% (95% HPD=17-27%). Study heterogeneity (tau2) was low, ranging from 0.046 to
      0.080. An incidental diagnosis of liver cirrhosis was reported in 15.6% of
      patients in one series. Five-year survival was similar between cirrhotic and non
      cirrhotic patients but was statistically significantly higher in patients with
      MELD score<10. CONCLUSIONS: Sound scientific evidence with regard to efficacy and
      outcomes of esophagectomy in patients with concomitant liver cirrhosis is
      lacking. There is a need to properly select these frail patients to reduce
      postoperative morbidity and mortality rates.

PMID- 29653855
TI  - Determination of Ra-226, Ra-228 and K-40 specific activities in samples of
      mineral fertilizers marketed in the city of Rio de Janeiro, Brazil.
AB  - Fertilizer samples were collected in the city of Rio de Janeiro and were analyzed
      using HPGe detector. The specific activities of Ra-226 ranged from 1.48 Bq/kg to
      597 Bq/kg, of Ra-228 from 2.66 Bq/kg to 832 Bq/kg and of K-40 from 16 Bq/kg to
      13941 Bq/kg. The risk to human health was found to be negligible.

PMID- 29653856
TI  - OSL properties of KMgF3:Tm3+ for dosimetric applications as OSL dosimeter.
AB  - The optically stimulated luminescence (OSL) properties of undoped and Tm3+-doped
      KMgF3 fluoroperovskite have been investigated for the first time. KMgF3 compounds
      were synthesized by solid state reaction method and two different procedures were
      employed to improve the contact among the reagents, namely, the compressed powder
      was put either in an alumina crucible or in a platinum foil. The maximum OSL
      emission was found in samples prepared in an alumina crucible and doped with 0.5%
      mol of thulium. The radioluminescence (RL) spectrum shows two emission peaks at
      455 and 360 nm, which can be ascribed to the 1D2-3F4 and 1D2-3H6 transitions of
      Tm3+ cations. The OSL dosimetric properties of the most promising composition,
      namely, KMgF3:Tm3+ (0.5% mol), have also been determined and analyzed. This
      compound exhibits good linearity in the dose range from 0.1 up to 100 Gy and
      satisfactory repeatability with a percentage standard deviation of 2.4%.
      Therefore, an OSL fading of approximately 75% in the first 36 h of storage is
      observed and then, the response remains almost constant. These characteristics,
      together with a minimum detectable dose of 0.04 Gy and the rapid erasing of the
      OSL signal after 100 s of stimulation, which makes feasible to bleach completely
      the residual OSL in order to restore the sample between dose measurements,
      suggest the potential of this perovskite as OSL dosimeter.

PMID- 29653857
TI  - A Randomized Phase II Study of FOLFOX6/Bevacizumab With or Without Pelareorep in
      Patients With Metastatic Colorectal Cancer: IND.210, a Canadian Cancer Trials
      Group Trial.
AB  - BACKGROUND: Oncolytic reovirus pelareorep might preferentially infect and destroy
      rat sarcoma (RAS)-activated cells, and has preclinical and early clinical
      activity against colorectal cancer (CRC). PATIENTS AND METHODS: After a 6-patient
      safety run-in, 103 patients with metastatic CRC were randomly assigned to
      standard first-line leucovorin/5-FU/oxaliplatin (FOLFOX6)/bevacizumab
      (FOLFOX/BEV) every 2 weeks with (n = 51) or without (n = 52) pelareorep 3 * 1010
      tissue culture infective dose 50 on days 1 to 5 (cycles 1, 2, 4, and alternate
      cycles thereafter). The primary end point was progression-free survival (PFS).
      Secondary end points included overall survival (OS), objective response rate
      (ORR), quality of life, and correlative analyses. RESULTS: At 13 months' median
      follow-up, PFS was inferior in the pelareorep arm (median 7 vs. 9 months; hazard
      ratio [HR], 1.59 [80% confidence interval (CI), 1.18-2.15]; P = .046). There was
      no statistical difference in OS (median, 19.2 vs. 20.1 months; HR, 1.22; P =
      .38). An increased ORR was observed with pelareorep (adjusted odds ratio, 2.52
      [80% CI, 1.44-4.41]; P = .03), but with a shorter median duration of response (5
      vs. 9 months; P = .028). Pelareorep patients experienced more hypertension and
      proteinuria, and were more likely to omit bevacizumab before progression. A trend
      to lower dose intensity and shorter oxaliplatin and bevacizumab treatment
      duration was observed with pelareorep. CONCLUSION: Combination pelareorep with
      FOLFOX/BEV was tolerable with an increased ORR, but PFS was inferior. Subgroup
      analysis of baseline variables including Kirsten rat sarcoma oncogene did not
      identify subgroups with PFS benefit. Decreased treatment intensity with standard
      agents likely contributed to the lack of benefit with pelareorep. Future studies
      might consider alternate pelareorep/chemotherapy strategies or combination
      therapy with novel agents.

PMID- 29653859
TI  - Chemodenervation for the Treatment of Facial Dystonia: A Report by the American
      Academy of Ophthalmology.
AB  - PURPOSE: To review the medical literature on the outcomes and complications of
      various Food and Drug Administration-approved botulinum toxins for benign
      essential blepharospasm (BEB) and hemifacial spasm (HFS). METHODS: Literature
      searches were last conducted in February 2017 in PubMed for articles published in
      English and in the Cochrane Library database without language limitations;
      studies published before 2000 were excluded. The combined searches yielded 127
      citations. Of these, 13 articles were deemed appropriate for inclusion in this
      assessment, and the panel methodologist assigned ratings to them according to the
      level of evidence. RESULTS: A combined total of 1523 patients (1143 with BEB and
      380 with HFS) were included in the 13 studies. Five studies provided level I
      evidence, 2 studies provided level II evidence, and 6 studies provided level III
      evidence. Pretarsal injections were more efficacious than preseptal injections
      (96% vs. 86%, respectively). Pretarsal injections also resulted in a higher
      response rate on clinical scales (P < 0.05) and a longer duration of maximum
      response for both HFS and BEB. Patients with HFS require lower overall doses of
      onabotulinumtoxinA than patients with BEB for a similar duration of effect.
      Adverse events were dose related, and they occurred more frequently in patients
      who were given more units. CONCLUSIONS: Level I evidence supports the efficacy of
      Botox (Allergan Corp., Irvine, CA), Meditoxin, and Xeomin (Merz Pharmaceuticals,
      Frankfurt am Main, Germany) for the treatment of BEB. Meditoxin and Botox have
      equivalent effectiveness and incidence of adverse events for BEB and HFS. Dysport
      (Ipsen Biopharmaceuticals, Inc, Paris, France) seems to have efficacy similar to
      Botox and Meditoxin for BEB and HFS, but any definitive conclusions from the 2
      level II studies in this review are limited by differences in the methodologies
      used. Higher doses of Botox and Dysport result in more adverse events. Repeated
      treatments using Botox seem to maintain efficacy for treatment of facial
      dystonias over a follow-up period of at least 10 years, based on level III
      evidence.

PMID- 29653858
TI  - Phase II Randomized, Double-Masked, Vehicle-Controlled Trial of Recombinant Human
      Nerve Growth Factor for Neurotrophic Keratitis.
AB  - PURPOSE: To evaluate the safety and efficacy of topical recombinant human nerve
      growth factor (rhNGF) for treating moderate-to-severe neurotrophic keratitis
      (NK), a rare degenerative corneal disease resulting from impaired corneal
      innervation. DESIGN: Phase II multicenter, randomized, double-masked, vehicle
      controlled trial. PARTICIPANTS: Patients with stage 2 (moderate) or stage 3
      (severe) NK in 1 eye. METHODS: The REPARO phase II study assessed safety and
      efficacy in 156 patients randomized 1:1:1 to rhNGF 10 MUg/ml, 20 MUg/ml, or
      vehicle. Treatment was administered 6 drops per day for 8 weeks. Patients then
      entered a 48- or 56-week follow-up period. Safety was assessed in all patients
      who received study treatment, whereas efficacy was by intention to treat. MAIN
      OUTCOME MEASURES: Corneal healing (defined as <0.5-mm maximum diameter of
      fluorescein staining in the lesion area) was assessed by masked central readers
      at week 4 (primary efficacy end point) and week 8 (key secondary end point) of
      controlled treatment. Corneal healing was reassessed post hoc by masked central
      readers using a more conservative measure (0-mm staining in the lesion area and
      no other persistent staining). RESULTS: At week 4 (primary end point), 19.6% of
      vehicle-treated patients achieved corneal healing (<0.5-mm lesion staining)
      versus 54.9% receiving rhNGF 10 MUg/ml (+35.3%; 97.06% confidence interval [CI],
      15.88-54.71; P < 0.001) and 58.0% receiving rhNGF 20 MUg/ml (+38.4%; 97.06% CI,
      18.96-57.83; P < 0.001). At week 8 (key secondary end point), 43.1% of vehicle
      treated patients achieved less than 0.5-mm lesion staining versus 74.5% receiving
      rhNGF 10 MUg/ml (+31.4%; 97.06% CI, 11.25-51.49; P = 0.001) and 74.0% receiving
      rhNGF 20 MUg/ml (+30.9%; 97.06% CI, 10.60-51.13; P = 0.002). Post hoc analysis of
      corneal healing by the more conservative measure (0-mm lesion staining and no
      other persistent staining) maintained statistically significant differences
      between rhNGF and vehicle at weeks 4 and 8. More than 96% of patients who healed
      after controlled rhNGF treatment remained recurrence free during follow-up.
      Treatment with rhNGF was well tolerated; adverse effects were mostly local, mild,
      and transient. CONCLUSIONS: Topical rhNGF is safe and more effective than vehicle
      in promoting healing of moderate-to-severe NK.

PMID- 29653860
TI  - A Deep Learning Algorithm for Prediction of Age-Related Eye Disease Study
      Severity Scale for Age-Related Macular Degeneration from Color Fundus
      Photography.
AB  - PURPOSE: Age-related macular degeneration (AMD) is a common threat to vision.
      While classification of disease stages is critical to understanding disease risk
      and progression, several systems based on color fundus photographs are known.
      Most of these require in-depth and time-consuming analysis of fundus images.
      Herein, we present an automated computer-based classification algorithm. DESIGN:
      Algorithm development for AMD classification based on a large collection of color
      fundus images. Validation is performed on a cross-sectional, population-based
      study. PARTICIPANTS: We included 120 656 manually graded color fundus images from
      3654 Age-Related Eye Disease Study (AREDS) participants. AREDS participants were
      >55 years of age, and non-AMD sight-threatening diseases were excluded at
      recruitment. In addition, performance of our algorithm was evaluated in 5555
      fundus images from the population-based Kooperative Gesundheitsforschung in der
      Region Augsburg (KORA; Cooperative Health Research in the Region of Augsburg)
      study. METHODS: We defined 13 classes (9 AREDS steps, 3 late AMD stages, and 1
      for ungradable images) and trained several convolution deep learning
      architectures. An ensemble of network architectures improved prediction accuracy.
      An independent dataset was used to evaluate the performance of our algorithm in a
      population-based study. MAIN OUTCOME MEASURES: kappa Statistics and accuracy to
      evaluate the concordance between predicted and expert human grader
      classification. RESULTS: A network ensemble of 6 different neural net
      architectures predicted the 13 classes in the AREDS test set with a quadratic
      weighted kappa of 92% (95% confidence interval, 89%-92%) and an overall accuracy
      of 63.3%. In the independent KORA dataset, images wrongly classified as AMD were
      mainly the result of a macular reflex observed in young individuals. By
      restricting the KORA analysis to individuals >55 years of age and prior exclusion
      of other retinopathies, the weighted and unweighted kappa increased to 50% and
      63%, respectively. Importantly, the algorithm detected 84.2% of all fundus images
      with definite signs of early or late AMD. Overall, 94.3% of healthy fundus images
      were classified correctly. CONCLUSIONS: Our deep learning algoritm revealed a
      weighted kappa outperforming human graders in the AREDS study and is suitable to
      classify AMD fundus images in other datasets using individuals >55 years of age.

PMID- 29653861
TI  - Phase I Trial of Recombinant Human Nerve Growth Factor for Neurotrophic
      Keratitis.

PMID- 29653862
TI  - Influence of low FODMAP and gluten-free diets on disease activity and intestinal
      microbiota in patients with non-celiac gluten sensitivity.
AB  - BACKGROUND & AIMS: Non-celiac gluten sensitivity (NCGS) is characterized by
      intestinal and extra-intestinal symptoms triggered by ingestion of gluten.
      However, non-gluten triggers have recently been implicated, and a FODMAP
      (fermentable oligo-, di-, monosaccharides and polyols)-reduced diet can partially
      improve symptoms in NCGS. Our aim was to analyze the effect of a low FODMAP
      versus a gluten-free diet (GFD) on clinical symptoms, psychological well-being,
      intestinal inflammation and integrity, and stool microbiota. METHODS: Nineteen
      patients with NCGS and ten healthy controls consumed a gluten-containing standard
      diet before starting a two-week low FODMAP diet; after a five day transition
      period, participants ingested a GFD for another two weeks. The primary outcome
      measure was the improvement of clinical symptoms in NCGS patients under the
      different diets. Secondary outcomes were the determination of dietary effects on
      intestinal inflammation, psychological well-being, and differences in stool
      microbiota between NCGS patients and controls. RESULTS: The low FODMAP diet and
      especially the GFD led to a significant improvement of clinical and psychological
      symptoms in NCGS. A clear reduction in duodenal intraepithelial lymphocytes and
      mucin-producing Goblet cells was found after the GFD in these patients.
      Significant microbial differences between NCGS patients and controls were noticed
      in stool samples at every time point. Both diets caused microbial shifts in all
      participants, with a greater variability on genus level and metabolisms groups in
      NCGS patients. CONCLUSIONS: Our findings suggest a multifactorial etiology of
      NCGS, due to a functional effect caused by FODMAPs, combined with a mild gluten
      triggered immune reaction, and a microbiota dysbalance. CLINICALTRIAL. GOV ID:
      NCT03268720.

PMID- 29653863
TI  - Associations of body adiposity index, waist circumference, and body mass index in
      young adults.
AB  - BACKGROUND & AIMS: The Body Adiposity Index (BAI) is an anthropometric measure
      developed to estimate body composition in field settings. Although this novel
      measure has been validated against clinical measures of adiposity (%Fat), the
      relative accuracy of other anthropometric measures, such as Body Mass Index
      (BMI), and waist circumference (WC), have not been assessed in comparison to the
      BAI using a 4-compartment (4C) model. PURPOSE: The primary aim of this study was
      to examine the association between BMI, WC, BAI, and %Fat in young adults, and
      determine the relative accuracy of each anthropometric measure when predicting
      %Fat. METHODS: BMI, WC, and BAI were assessed in a sample of young adults (n =
      188, 48.4% female, 21.8 +/- 4.8 years). %Fat assessed using the 4C model was
      derived from underwater weighing for body density, dual-energy X-ray
      absorptiometry for bone mineral content, and bioimpedance spectroscopy for total
      body water. Bivariate associations were assessed using Pearson's r, with the
      relative accuracy of each measure assessed using multivariate linear regression
      and compared using Akaike's information criterion, R2 and DeltaR2 statistics.
      RESULTS: BMI, WC, and BAI were associated with %Fat (r = 0.192, 0.194, and 0.668,
      respectively, all p < .01). WC and BAI collectively explained 46.3% of the
      variation in %Fat, and removing BAI significantly reduced model fit (p < .001).
      When stratified by sex, BAI provided greater accuracy when predicting %Fat beyond
      WC in men (DeltaR2 = 2.6%, p = .022), but not women (DeltaR2 = 2.1%, p = .078).
      CONCLUSION: WC and BAI are more strongly associated with %Fat as measured by the
      4C model than BMI in young adults.

PMID- 29653864
TI  - Opinions and practices of healthcare professionals on assessment of disease
      associated malnutrition in children: Results from an international survey.
AB  - BACKGROUND & AIMS: Lack of consensus on clinical indicators for the assessment of
      pediatric disease associated malnutrition (DAM) may explain its under-recognition
      in clinical practice. This study surveyed the opinions of health professionals
      (HP) on clinical indicators of DAM and barriers impeding routine nutritional
      screening in children. METHODS: Web-based questionnaire survey (April 2013-August
      2015) in Australia, Belgium, Israel, Spain, The Netherlands, Turkey and UK.
      RESULTS: There were 937 questionnaires returned via local professional
      associations, of which 693 respondents fulfilled the inclusion criteria and were
      included in the final analysis; 315 pediatric gastroenterologists and 378
      pediatric dieticians. The most important clinical indicators of DAM were ongoing
      weight loss (80.4%), increased energy/nutrient losses (73.0%), suboptimal
      energy/macronutrient intake (68.6%), a high nutritional risk condition (67.2%)
      and increased energy/nutrient requirements (66.2%). These findings were
      consistent across countries and professions. The most common approach to screen
      for DAM was assessment of weight changes (85%), followed by the usage of growth
      charts (77-80%). Common perceived barriers for routine nutritional
      screening/assessment were low staff awareness (47.5%), no local policy or
      guidelines (33.4%) and lack of time to screen (33.4%). CONCLUSIONS: HP who
      routinely assess and treat children with DAM identified ongoing weight loss,
      increased losses, increased requirements, low intake and high nutritional risk
      conditions as the most important clinical indicators of DAM. These clinical
      indicators should now serve as a basis to form clinical-based criteria for the
      identification of DAM in routine clinical practice. Low awareness, lack of
      guidelines or local policy and lack of resources were the most important barriers
      of routine screening.

PMID- 29653865
TI  - Vaccination status and needs of asylum-seeking children in Denmark: a
      retrospective data analysis.
AB  - OBJECTIVES: Asylum seekers to Europe may come from war-torn countries where
      health systems have broken down, and there is evidence that asylum-seeking
      children have low coverage of childhood vaccinations, as well as uptake of
      immunisations in host countries. Such gaps in immunisation have important
      implications for effective national vaccination programmes. How we approach
      vaccination in children and adults entering Western Europe, where as a group they
      face barriers to health services and screening, is a growing debate; however,
      there are limited data on the vaccination status of these hard-to-reach
      communities, and robust evidence is needed to inform immunisation strategies. The
      aim of this study was to explore the vaccination status and needs of asylum
      seeking children and adolescents in Denmark. STUDY DESIGN: We conducted a
      retrospective data analysis of anonymised patient records for asylum-seeking
      children and adolescents extracted from the Danish Red Cross database. METHODS:
      We retrospectively searched the Danish Red Cross database for children and
      adolescents (aged 3 months-17 years) with active asylum applications in Denmark
      as of October 28, 2015. Data were extracted for demographic characteristics,
      vaccination status and vaccinations needed by asylum-seeking children presenting
      to Red Cross asylum centres for routine statutory health screening. RESULTS: We
      explored the vaccination status and needs of 2126 asylum-seeking children and
      adolescents. About 64% of the study population were male and 36% were female.
      Eight nationalities were represented, where 33% of the total of children and
      adolescents were not immunised in accordance with Danish national guidelines,
      while 7% were considered partly vaccinated, and 60% were considered adequately
      vaccinated. Afghan (57% not vaccinated/unknown) and Eritrean (54% not
      vaccinated/unknown) children were the least likely to be vaccinated of all
      nationalities represented, as were boys (37% not vaccinated/unknown) compared
      with girls (27% not vaccinated/unknown) and children and adolescents aged between
      12 and 17 years (48% not vaccinated/unknown) compared with 6- to 11-year olds
      (26%) and 0- to 5-year olds (22%). The health screenings resulted in 1328
      vaccinations. The most commonly needed vaccines were diphtheria, tetanus,
      pertussis, polio and Haemophilus influenzae type b, (DTaP/IPV/Hib) which
      comprised 49% of the vaccines distributed, followed by the pneumococcal vaccine
      (Prevnar) (28%) and measles, mumps and rubella (MMR) vaccine (23%). CONCLUSIONS:
      The finding that nearly one-third of asylum-seeking children and adolescents in
      Denmark were in need of further vaccinations highlights the gaps in immunisation
      coverage in these populations. These results point to the need to improve access
      to health services and promote national vaccine programmes targeted at these
      communities to facilitate vaccination uptake and increase immunisation coverage
      to reduce the risk of preventable infectious diseases among asylum-seeking
      children.

PMID- 29653866
TI  - Structural violence and marginalisation. The sexual and reproductive health
      experiences of separated young people on the move. A rapid review with relevance
      to the European humanitarian crisis.
AB  - OBJECTIVE: To explore the main sexual and reproductive health (SRH) issues for
      separated young migrants. STUDY DESIGN: We conducted a rapid review. METHODS: The
      search for articles published between 2000 and June 2017 including peer-reviewed
      and 'grey' published literature from a range of databases including MEDLINE,
      AMED, Embase, ASSIA, Scopus, Web of Science and websites of international
      organisations (Missing Children Alliance, United Nations Population Fund (UNFPA),
      World Health Organization (WHO), United Nations Human Rights Council (UNHRC),
      Human Rights Watch, United Nations Children's Fund (UNICEF) and FBX Centre for
      Health and Human Rights) took place over 4 months. Themes emerging from the
      included studies and articles were synthesised. RESULTS: We found 44 articles
      from a range of countries of which 64% were peer-reviewed and 36% were from
      'grey' literature. Structural violence and marginalisation were the key
      analytical themes that emerged and included young people's vulnerability to
      violence, unmet knowledge and service needs, barriers and stigma and poor SRH
      outcomes. CONCLUSIONS: This is the first known review to summarise the key SRH
      issues for separated young migrants. As Europe hosts the greatest number of
      separated young people in recent history, their unique SRH concerns risk being
      overlooked. Public health practitioners and policy makers are encouraged to
      challenge the gaps that exist in their services.

PMID- 29653867
TI  - Migration and its influence on the knowledge and usage of birth control methods
      among Afghan women who stay behind.
AB  - OBJECTIVE: The objective of this article is to investigate the link between
      migration and knowledge and use of birth control methods among female household
      members (of migrants) who stay behind in Afghanistan. Migrants can remit birth
      control information received in the destination country to non-migrants staying
      in the origin country, who may as a consequence adjust their health behaviour
      accordingly. The consequences of this interaction for knowledge and use are what
      we aim to test. STUDY DESIGN: Population-based secondary analysis of cross
      sectional data. METHODS: This study used cross-sectional data from the Afghan
      Mortality Survey (2010). Using ordinary least squares regression and propensity
      score matching, this research studies to what extent having a migrant in the
      household influences the knowledge and use of birth control among non-migrant
      Afghan women. Women who stay behind are defined in this research as those with a
      migrant household member who moved between 2005 and 2010. RESULTS: Results
      indicated that non-Pashtun women with a migrant household member showed greater
      knowledge of contraceptive methods using injectables, birth control pill and
      lactational amenorrhea method compared to those women without a migrant household
      member. Less knowledge of male sterilisation and emergency contraception is
      observed for all women (both Pashtun and non-Pashtun) with a migrant in their
      household on male sterilisation and emergency contraception compared to the women
      without a migrant in the household. In addition, we show that Pashtun women with
      a migrant in the household had lower levels of overall knowledge and were less
      likely to use birth control methods than women without a migrant household
      member. CONCLUSION: In Afghanistan, given the proximity, religious similarity and
      sociocultural customs mainly men migrate either to Pakistan or Iran. The findings
      suggest that migrants in different destination countries transfer different
      information (or fail to successfully transfer information) about birth control
      methods to members of their transnational networks, compounding disparities in
      knowledge and use of birth control methods among women staying in the origin
      country. Migrants have the potential to be health-related development agents, but
      the health information migrants receive while abroad and remit back to their home
      countries varies by destination country context.

PMID- 29653868
TI  - Clinicopathological investigation of odontogenic fibroma in tuberous sclerosis
      complex.
AB  - Tuberous sclerosis complex (TSC) is an autosomal dominant inherited disease
      characterized by systemic hamartoma and diverse systemic features. TSC1 and TSC2
      are the causative genes, and mental retardation, epileptic seizures, and facial
      angiofibroma develop in many patients with the disease. The case of a patient
      with TSC who developed a central odontogenic fibroma of the mandible is reported
      here. The patient was a 21-year-old woman who was referred with a swelling of the
      labial gingiva in the region of the right lower lateral incisor and canine.
      Dental radiography revealed a multilocular radiolucent region with a clear
      boundary. The right lower lateral incisor and canine were continuous with the
      lesion and thus were excised en bloc. The lesion was encapsulated and easily
      dissected. The diagnosis on immunohistological staining was odontogenic fibroma
      without an epithelial component. TSC1/2 gene mutation causes abnormal activation
      of mammalian target of rapamycin (mTOR) downstream of the PI3K-AKT pathway. The
      odontogenic fibroma in this patient was positive for mTOR, suggesting that the
      development of the odontogenic fibroma was the result of abnormal activation of
      mTOR, as in angiofibroma. The clinical course of this patient is presented and
      the developmental mechanism of central odontogenic fibroma is discussed.

PMID- 29653869
TI  - Assessing an oral surgery specific protocol for patients on direct oral
      anticoagulants: a retrospective controlled cohort study.
AB  - Chronic therapy with the new direct oral anticoagulants (DOACs) poses new
      challenges for dental practitioners assessing the risk versus benefit of
      cessation versus non-cessation of anticoagulant therapy for dentoalveolar
      procedures. A retrospective controlled cohort study was designed to evaluate a
      non-cessation protocol for patients taking DOACs in the setting of dental
      extractions. A records review covering the period 1 January 2016 to 31 December
      2016 identified 43 patients on DOAC therapy; 53 dentoalveolar procedures were
      performed under local anaesthesia, of which 15 included varying degrees of peri
      procedural cessation. A control group of 50 patients on uninterrupted warfarin
      therapy undergoing 59 dentoalveolar procedures was identified. The incidence,
      severity, and timing of bleeding events were recorded for each group. Four
      (10.5%) minor bleeding events were recorded in the non-cessation DOAC group and
      nine (15.3%) minor bleeding events in the warfarin group. No bleeding events were
      recorded in the DOAC cessation group. Comparison of the incidence of bleeding
      events between the non-cessation DOAC group and the warfarin group showed no
      statistically significant difference (odds ratio 0.65, P=0.56). Within the
      limitations of this study, dental extractions in the context of continuing DOAC
      therapy can be performed safely provided extra local haemostatic measures are
      applied.

PMID- 29653870
TI  - Palatal orthodontic miniscrew insertion using a CAD-CAM surgical guide:
      description of a technique.
AB  - The aim of this report was to describe a new computer-guided technique for a
      controlled site preparation and palatal orthodontic miniscrew insertion using a
      dedicated software. A surgical guide was designed after planning the appropriate
      insertion sites on three-dimensional images created by the fusion of cone-beam
      computed tomography (CBCT) and digital dental model images. Pre- and
      postoperative CBCT images were compared and the angular, coronal, and apical
      deviations between the planned and the placed miniscrews were calculated. The
      mean coronal and apical deviations were 1.38mm (range: 3.48-0.15mm; standard
      deviation (SD): 0.65) and 1.73mm (range: 5.41-0.10mm; SD: 1.03), respectively,
      while the mean angular deviation was 4.60 degrees  (range: 15.23-0.54 degrees ;
      SD: 2.54). The present surgical guide allows a controlled and accurate palatal
      miniscrew placement in three dimensions.

PMID- 29653872
TI  - Facile synthesis of semi-library of low charge density cationic polyesters from
      poly(alkylene maleate)s for efficient local gene delivery.
AB  - Cationic polymers are one of the main non-viral vectors for gene therapy, but
      their applications are hindered by the toxicity and inefficient transfection,
      particularly in the presence of serum or other biological fluids. While rational
      design based on the current understanding of gene delivery process has produced
      various cationic polymers with improved overall transfection, high-throughput
      parallel synthesis of libraries of cationic polymers seems a more effective
      strategy to screen out efficacious polymers. Herein, we demonstrate a novel
      platform for parallel synthesis of low cationic charge-density polyesters for
      efficient gene delivery. Unsaturated polyester poly(alkylene maleate) (PAM)
      readily underwent Michael-addition reactions with various mercaptamines to
      produce polyester backbones with pendant amine groups, poly(alkylene maleate
      mercaptamine)s (PAMAs). Variations of the alkylenes in the backbone and the
      mercaptamines on the side chain produced PAMAs with tunable hydrophobicity and
      DNA-condensation ability, the key parameters dominating transfection efficiency
      of the resulting polymer/DNA complexes (polyplexes). A semi-library of such PAMAs
      was exampled from 7 alkylenes and 18 mercaptamines, from which a lead PAMA, G-1,
      synthesized from poly(1,4-phenylene bis(methylene) maleate) and N,N
      dimethylcysteamine, showed remarkable transfection efficiency even in the
      presence of serum, owing to its efficient lysosome-circumventing cellular uptake.
      Furthermore, G-1 polyplexes efficiently delivered the suicide gene pTRAIL to
      intraperitoneal tumors and elicited effective anticancer activity.

PMID- 29653871
TI  - Photopolymerized dynamic hydrogels with tunable viscoelastic properties through
      thioester exchange.
AB  - The extracellular matrix (ECM) constitutes a viscoelastic environment for cells.
      A growing body of evidence suggests that the behavior of cells cultured in
      naturally-derived or synthetic ECM mimics is influenced by the viscoelastic
      properties of these substrates. Adaptable crosslinking strategies provide a means
      to capture the viscoelasticity found in native soft tissues. In this work, we
      present a covalent adaptable hydrogel based on thioester exchange as a
      biomaterial for the in vitro culture of human mesenchymal stem cells. Through
      control of pH, gel stoichiometry, and crosslinker structure, viscoelastic
      properties in these crosslinked networks can be modulated across several orders
      of magnitude. We also propose a strategy to alter these properties in existing
      networks by the photo-uncaging of the catalyst 4-mercaptophenylacetic acid.
      Mesenchymal stem cells encapsulated in thioester hydrogels are able to elongate
      in 3D and display increased proliferation relative to those in static networks.

PMID- 29653873
TI  - Long-term risk of dementia among people with traumatic brain injury in Denmark: a
      population-based observational cohort study.
AB  - BACKGROUND: Traumatic brain injury (TBI) has been associated with increased risk
      of dementia; however, large-scale studies with long follow-up have been scarce.
      We investigated the association between TBI, including severity and number of
      TBIs, and the subsequent long-term risk of dementia. METHODS: We did a nationwide
      population-based observational cohort study in Denmark using information on
      citizens from national registries. We used the Danish Civil Registration System
      to establish a population-based cohort consisting of all people born in Denmark
      who were living in the country on Jan 1, 1995, and who were at least 50 years old
      at some point during follow-up (between 1999 and 2013). We obtained information
      on TBIs from the Danish National Patient Register (NPR), and obtained information
      on dementia by combining data recorded in the NPR, the Danish Psychiatric Central
      Register, and the Danish National Prescription Registry (DNPR). The long-term
      risk of dementia after TBI was established using survival analysis. We used three
      prespecified models for each of the three analyses: different time periods since
      the TBI, multiple TBIs, and sex. The first model adjusted for sociodemographic
      factors, the second model added medical and neurological comorbidities, and the
      third added psychiatric comorbidities. FINDINGS: We used data from a cohort of 2
      794 852 people for a total of 27 632 020 person-years (mean 9.89 years per
      patient) at risk of dementia. 132 093 individuals (4.7%) had at least one TBI
      during 1977-2013, and 126 734 (4.5%) had incident dementia during 1999-2013. The
      fully adjusted risk of all-cause dementia in people with a history of TBI was
      higher (hazard ratio [HR] 1.24, 95% CI 1.21-1.27) than in those without a history
      of TBI, as was the specific risk of Alzheimer's disease (1.16, 1.12-1.22). The
      risk of dementia was highest in the first 6 months after TBI (HR 4.06, 3.79-4.34)
      and also increased with increasing number of events (1.22, 1.19-1.25 with one TBI
      to 2.83, 2.14-3.75 with five or more TBIs). Furthermore, TBI was associated with
      a higher risk of dementia (1.29, 1.26-1.33) in people with TBI than in
      individuals with a non-TBI fracture not involving the skull or spine. The younger
      a person was when sustaining a TBI, the higher the HRs for dementia when
      stratified by time since TBI. INTERPRETATION: TBI was associated with an
      increased risk of dementia both compared with people without a history of TBI and
      with people with non-TBI trauma. Greater efforts to prevent TBI and identify
      strategies to ameliorate the risk and impact of subsequent dementia are needed.
      FUNDING: Lundbeck Foundation.

PMID- 29653874
TI  - Traumatic brain injury and dementia.

PMID- 29653875
TI  - Toward precision manufacturing of immunogene T-cell therapies.
AB  - Cancer can be effectively targeted using a patient's own T cells equipped with
      synthetic receptors, including chimeric antigen receptors (CARs) that redirect
      and reprogram these lymphocytes to mediate tumor rejection. Over the past two
      decades, several strategies to manufacture genetically engineered T cells have
      been proposed, with the goal of generating optimally functional cellular products
      for adoptive transfer. Based on this work, protocols for manufacturing clinical
      grade CAR T cells have been established, but these complex methods have been used
      to treat only a few hundred individuals. As CAR T-cell therapy progresses into
      later-phase clinical trials and becomes an option for more patients, a major
      consideration for academic institutions and industry is developing robust
      manufacturing processes that will permit scaling-out production of immunogene T
      cell therapies in a reproducible and efficient manner. In this review, we will
      discuss the steps involved in cell processing, the major obstacles surrounding T
      cell manufacturing platforms and the approaches for improving cellular product
      potency. Finally, we will address the challenges of expanding CAR T-cell therapy
      to a global patient population.

PMID- 29653876
TI  - Artificial intelligence in clinical imaging: An introduction.

PMID- 29653877
TI  - Anaphylaxis in late pregnancy: plasma concentrations of histamine, tryptase and
      IgE in the neonate.

PMID- 29653878
TI  - Argon laser peripheral iridoplasty and anterior segment optical coherence
      tomography in the management of acute angle closure in the 21st century.

PMID- 29653879
TI  - [Acquired hemophilia A associated with chronic myelomonocytic leukemia
      successfully treated by rituximab and azacitidine].
AB  - INTRODUCTION: Acquired hemophilia A is a factor VIII deficiency related to anti
      factor VIII immunoglobulins. We are reporting the case of a patient with acquired
      hemophilia A related to chronic myelomonocytic leukemia. CASE REPORT: A 74-years
      old woman had a spontaneous calf hematoma with compression syndrome. Coagulation
      tests revealed an extended partial thromboplastin time and a factor VIII
      deficiency with circulating factor VIII antibodies. Chronic myelomonocytic
      leukemia was diagnosed in the same time. Initial management included hemostatic
      transfusion and steroids and was completed rituximab and azacitidine. Evolution
      was favorable. CONCLUSION: We report a case of acquired hemophilia A complicating
      a chronic myelomonocytic leukemia. Management with steroids, rituximab and
      azacitidine was successful. Useful of rituximab during acquired hemophilia is
      proposed.

PMID- 29653881
TI  - Battlefield to Bedside: Bringing Precision Medicine to Surgical Care.

PMID- 29653880
TI  - Gastric parietal cell and thyroid autoantibodies in Behcet's disease patients
      with or without atrophic glossitis.
AB  - BACKGROUND/PURPOSE: Behcet's disease (BD) patients should have recurrent aphthous
      stomatitis (RAS) but they may or may not have atrophic glossitis (AG). This study
      mainly assessed the frequencies of serum gastric parietal cell antibody (GPCA),
      thyroglobulin antibody (TGA), and thyroid microsomal antibody (TMA) positivities
      in 30 AG-positive RAS/BD (AG+RAS/BD) and 33 AG-negative RAS/BD (AG?RAS/BD)
      patients. METHODS: The frequencies of serum GPCA, TGA, and TMA positivities in 30
      AG+RAS/BD patients, 33 AG?RAS/BD patients, and 126 healthy control subjects were
      calculated and compared. RESULTS: We found that 20.0%, 30.0%, and 26.7% of 30
      AG+RAS/BD patients, 9.1%, 12.1%, and 15.2% of 33 AG?RAS/BD patients, and 1.6%,
      2.4%, and 2.4% of 126 healthy control subject had the presence of GPCA, TGA, and
      TMA in their sera, respectively. The 30 AG+RAS/BD patients had significantly
      higher frequencies of serum GPCA, TGA, and TMA positivities than healthy control
      subjects (all P-values < 0.001). The 33 AG?RAS/BD patients had a higher frequency
      of serum TGA positivity (P = 0.051, marginal significance) and a significantly
      higher frequency of serum TMA positivity (P = 0.011) than healthy control
      subjects. Although the 30 AG+RAS/BD patients had higher frequencies of serum
      GPCA, TGA, and TMA positivities than the 33 AG?RAS/BD patients, the differences
      were not significant. CONCLUSION: AG+RAS/BD patients do have significantly higher
      frequencies of serum GPCA, TGA, and TMA positivities than healthy control
      subjects. This finding indicates that the concomitant presence of AG may result
      in significantly elevated frequencies of serum GPCA, TGA, and TMA positivities in
      BD patients.

PMID- 29653882
TI  - Physical and chemical properties of pyrolyzed biosolids for utilization in sand
      based turfgrass rootzones.
AB  - Biosolids are several forms of treated sewage sludge that are intended for use as
      soil conditioners for horticultural, agricultural and industrial crops. The
      objectives of this research were to determine the chemical and physical
      properties of biosolids pyrolyzed at several different temperatures, and their
      effect on perennial ryegrass seed germination and growth. Biosolids were
      thermally treated in an oxygen-free (nitrogen atmosphere) retort oven at 300,
      400, 500, 700 and 900  degrees C. As pyrolysis temperatures increased, bulk
      densities, total surface areas, micropore surface areas, % minerals and pH values
      of the pyrolyzed biosolids increased, while carbon percentage decreased compared
      to untreated biosolids. Fourier-transform infrared spectroscopy analysis showed
      decreased surface functionality as pyrolysis temperature increased. Perennial
      ryegrass (Lolium perenne L. 'Nui') plants were grown in mixtures of 10% (v/v)
      biosolids or 10% (v/v) of the various pyrolyzed biosolids and 90% coarse sand.
      Ryegrass plants grown in the biosolids and the 300  degrees C pyrolyzed biosolids
      mixture had the greatest shoot heights of any of the treatments after 4 weeks of
      growth. These results indicate that pyrolyzing biosolids at 300  degrees C would
      produce material with excellent potential as a long-term peat replacement for
      water and nutrient retention in sand-based rootzones.

PMID- 29653883
TI  - Characterization of herb residue and high ash-containing paper sludge blends from
      fixed bed pyrolysis.
AB  - High ash-containing paper sludge which is rich in various metal oxides is
      employed in herb residue pyrolysis to enhance the yield of fuel gas and reduce
      tar yield in a drop tube fixed bed reactor. Effects of heat treatment temperature
      and blending ratio of paper sludge on the yields and composition of pyrolysis
      products (gas, tar and char) were investigated. Results indicate that paper
      sludge shows a significantly catalytic effect during the pyrolysis processes of
      herb residue, accelerating the pyrolysis reactions. The catalytic effect resulted
      in an increase in gas yield but a decrease in tar yield. The catalytic effect
      degree is affected by the paper sludge proportions, and the strongest catalytic
      effect of paper sludge is noted at its blending ratio of 50%. At temperature
      lower than 900  degrees C, the catalytic effect of paper sludge in the pyrolysis
      of herb residue promotes the formation of H2 and CO2, inhibits the formation of
      CH4, but shows slight influence on the formations of CO, while the formation of
      the four gas components was all promoted at 900  degrees C. SEM results of
      residue char show that ash particles from paper sludge adhere to the surface of
      the herb residue char after pyrolysis, which may promote the pyrolysis process of
      herb residue for more gas releasing. FT-IR results indicate that most functional
      groups disappear after pyrolysis. The addition of paper sludge promotes
      deoxidisation and aromatization reactions of hetero atoms tars, forming heavier
      polycyclic aromatic hydrocarbons and leading to tar yield decrease.

PMID- 29653884
TI  - Re: Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer.

PMID- 29653885
TI  - Who Should Be Investigated for Haematuria? Results of a Contemporary Prospective
      Observational Study of 3556 Patients.
AB  - : There remains a lack of consensus among guideline relating to which patients
      require investigation for haematuria. We determined the incidence of urinary
      tract cancer in a prospective observational study of 3556 patients referred for
      investigation of haematuria across 40 hospitals between March 2016 and June 2017
      (DETECT 1; ClinicalTrials.gov: NCT02676180) and the appropriateness of age at
      presentation in cases with visible (VH) and nonvisible (NVH) haematuria. The
      overall incidence of urinary tract cancer was 10.0% (bladder cancer 8.0%, renal
      parenchymal cancer 1.0%, upper tract transitional cell carcinoma 0.7%, and
      prostate cancer 0.3%). Patients with VH were more likely to have a diagnosis of
      urinary tract cancer compared with NVH patients (13.8% vs 3.1%). Older patients,
      male gender, and smoking history were independently associated with urinary tract
      cancer diagnosis. Of bladder cancers diagnosed following NVH, 59.4% were high
      risk cancers, with 31.3% being muscle invasive. The incidence of cancer in VH
      patients <45 yr of age was 3.5% (n=7) and 1.0% (n=4) in NVH patients <60 yr old.
      Our results suggest that patients with VH should be investigated regardless of
      age. Although the risk of urinary tract cancer in NVH patients is low, clinically
      significant cancers are detected below the age threshold for referral for
      investigation. PATIENT SUMMARY: This study highlights the requirement to
      investigate all patients with visible blood in the urine and an age threshold of
      >=60 yr, as recommended in some guidelines, as the investigation of nonvisible
      blood in the urine will miss a significant number of urinary tract cancers.
      Patient preference is important, and evidence that patients are willing to submit
      to investigation should be considered in reaching a consensus recommendation for
      the investigation of haematuria. International consensus to guide that patients
      will benefit from investigation should be developed.

PMID- 29653886
TI  - Improving the Cost Efficiency of PD-1/PD-L1 Inhibitors for Advanced Urothelial
      Carcinoma: A Major Role for Precision Medicine?

PMID- 29653887
TI  - Therapeutic hypothermia and pressure ulcer risk in critically ill intensive care
      patients: A retrospective study.
AB  - OBJECTIVE: To examine the role of therapeutic hypothermia in pressure ulcer
      development in critically ill patients. RESEARCH METHODOLOGY: Retrospective study
      in a mixed intensive care unit over 2010-2013. The incidences of pressure ulcers
      among patients treated with therapeutic hypothermia (n = 148) and the non
      hypothermia patient population (n = 6197) were compared. RESULTS: Patients
      treated with hypothermia developed more pressure ulcers (25.0%) than the non
      hypothermia group 6.3% (p < 0.001). More patients in the hypothermia group were
      rated as the high pressure ulcer risk group, as defined by the modified
      Jackson/Cubbin (mJ/C) risk score <=29 than the rest of the patients. Among the
      therapeutic hypothermia patients more pressure ulcers tended to emerge in the
      lower risk group (mJ/C score >=30) (p = 0.056). Intensive care mortality was
      higher in the hypothermia (24.3%) than the non-hypothermia group (9.3%, p <
      0.0001). CONCLUSION: Patients treated with therapeutic hypothermia should be
      considered at high risk for pressure ulcer development and should be managed
      accordingly. The hypothermia may not as such increase the risk for pressure
      ulcers, but combined with the severity of the underlying illness, may be more
      likely. The pressure ulcer risk in this patient group cannot be reliably assessed
      by the Jackson/Cubbin risk scale.

PMID- 29653888
TI  - Factors associated with unplanned extubation in the Intensive Care Unit for adult
      patients: A systematic review and meta-analysis.
AB  - OBJECTIVES: To explore factors associated with unplanned extubation in Intensive
      Care Unit for adult patients. RESEARCH METHODOLOGY: A systematic review and meta
      analysis were performed of studies identified through Pubmed, CINAHL, Cochrane
      Library, PsycINFO and Web of Science published from initiation to September 2017.
      Only articles in English were included. The Newcastle-Ottawa Scale was used to
      evaluate the quality of the included articles. RESULTS: Ten eligible studies were
      identified, encompassing a total of 2092 patients (457 in the unplanned
      extubation group; 1635 in the control group). The subsequent meta-analysis
      identified significant risk factors for unplanned extubation are male [odds ratio
      (OR) 1.54, 95% CI 1.12-2.12; P = 0.008], confusion [OR 0.10, 95% CI 0.05-0.17; P
      < 0.00001], physical restraint [OR 3.10, 95% CI 2.21-4.34; P < 0.00001], higher
      GCS scores [mean difference (MD) 1.06, 95% CI 0.59-1.52; P < 0.00001] and lower
      APACHE II scores [MD -2.26, 95% CI -3.35- -1.16; P < 0.0001]. Renal disease is a
      protective factor for unplanned extubation [OR 0.32, 95% CI 0.15-0.70; P =
      0.004]. CONCLUSION: Patients were male, confused, having physical restraint, with
      higher GCS and lower APACHE II scores are significant risk factors for unplanned
      extubation in Intensive Care Unit adult patients.

PMID- 29653889
TI  - Novel technique for fabrication of pneumatic ocular prosthesis.

PMID- 29653890
TI  - Summary of grip strength measurements obtained in the 2011-2012 and 2013-2014
      National Health and Nutrition Examination Surveys.
AB  - STUDY DESIGN: Cross-sectional and descriptive study. INTRODUCTION: Supported by
      the Centers for Disease Control and Prevention, the National Health and Nutrition
      Examination Survey (NHANES) began collecting grip strength data from nationally
      representative samples in 2011. PURPOSE OF THE STUDY: To examine the stability of
      the grip strength values across 2 data release cycles and provide updated US
      population-based grip strength values for 6 to 80 year olds. METHODS: Handgrip
      data from 13,676 participants aged 6-80 years were extracted from the NHANES 2011
      2014 database. The muscle strength/grip test component measured the isometric
      grip strength using a Takei digital handgrip dynamometer (Takei Scientific
      Instruments, Shinagawa-Ku, Tokyo). Grip strength values (best of 3 trials for
      each hand) were summarized by gender, dominant side, and age group. Grip data
      from 2 data release cycles (2011-2012 vs 2013-2014) were compared. RESULTS:
      Differences between 2 data release cycles were negligible. Hence, we summarize
      grip strength values across the entire 2011-2014 period. The mean grip strength
      ranged from 50.3 kg for the dominant hand of 30- to 34-year-old men to 10.0 kg
      for the nondominant hand of 6-year-old girls. DISCUSSION: The summary data we
      present provide relatively current reference values to which tested individuals
      can be compared. However, clinicians and/or researchers should be aware that the
      instrumentation and procedures may influence the values. CONCLUSIONS: Results
      supported the stability of the NHANES grip strength values across data release
      cycles.

PMID- 29653891
TI  - Brain functional connectivity of meaning attribution in patients with psychosis:
      Preliminary electroencephalographic observations.

PMID- 29653892
TI  - Comprehensive pathway analyses of schizophrenia risk loci point to dysfunctional
      postsynaptic signaling.
AB  - Large-scale genome-wide association studies (GWAS) have implicated many low
      penetrance loci in schizophrenia. However, its pathological mechanisms are poorly
      understood, which in turn hampers the development of novel pharmacological
      treatments. Pathway and gene set analyses carry the potential to generate
      hypotheses about disease mechanisms and have provided biological context to
      genome-wide data of schizophrenia. We aimed to examine which biological processes
      are likely candidates to underlie schizophrenia by integrating novel and powerful
      pathway analysis tools using data from the largest Psychiatric Genomics
      Consortium schizophrenia GWAS (N=79,845) and the most recent 2018 schizophrenia
      GWAS (N=105,318). By applying a primary unbiased analysis (Multi-marker Analysis
      of GenoMic Annotation; MAGMA) to weigh the role of biological processes from the
      Molecular Signatures Database (MSigDB), we identified enrichment of common
      variants in synaptic plasticity and neuron differentiation gene sets. We
      supported these findings using MAGMA, Meta-Analysis Gene-set Enrichment of
      variaNT Associations (MAGENTA) and Interval Enrichment Analysis (INRICH) on
      detailed synaptic signaling pathways from the Kyoto Encyclopedia of Genes and
      Genomes (KEGG) and found enrichment in mainly the dopaminergic and cholinergic
      synapses. Moreover, shared genes involved in these neurotransmitter systems had a
      large contribution to the observed enrichment, protein products of top genes in
      these pathways showed more direct and indirect interactions than expected by
      chance, and expression profiles of these genes were largely similar among brain
      tissues. In conclusion, we provide strong and consistent genetics and protein
      interaction informed evidence for the role of postsynaptic signaling processes in
      schizophrenia, opening avenues for future translational and psychopharmacological
      studies.

PMID- 29653893
TI  - Interaction between childhood adversity and functional polymorphisms in the
      dopamine pathway on first-episode psychosis.
AB  - BACKGROUND: There is consistent evidence of a cumulative relationship between
      childhood adversity and psychosis, with number of adversities experienced
      increasing the probability of psychosis onset. It is possible that genetic
      factors moderate the association between childhood adversity and psychosis,
      potentially by influencing how an individual reacts biologically and/or
      psychologically following exposure to adversity, in such a way as to set them off
      on the path to psychosis. However, identifying the specific genetic variants
      involved and how they interact with childhood adversity remains challenging. We
      examined whether the association between cumulative exposure to childhood
      adversity and development of psychotic disorder was moderated by the COMT
      Val158Met, AKT1 rs2494732 or DRD2 rs1076560 polymorphisms, known to affect
      dopamine levels. METHODS: Participants were 285 first-presentation psychosis
      cases and 256 geographically-matched controls drawn from the Genetics and
      Psychosis (GAP) study. Childhood adversity was assessed using the Childhood
      Experience of Care and Abuse Questionnaire (CECA.Q) and blood- and cheek-derived
      genotype data were collected. RESULTS: Our findings revealed no main effect of
      COMT Val158Met, AKT1 rs2494732 and DRD2 rs1076560 polymorphisms on psychosis case
      status or reports of childhood adversity. Individuals reporting a history of
      multiple adversities were more likely to be psychosis patients than controls,
      regardless of their genetic risk. There was no evidence of candidate genotype by
      childhood adversity interactions in relation to psychosis onset. CONCLUSION:
      These findings did not provide evidence of a possible role of COMT Val158Met,
      AKT1 rs2494732 or DRD2 rs1076560 genotypes in modifying the association between
      childhood adversity and onset of psychosis.

PMID- 29653894
TI  - MK-8325: A silyl proline-containing NS5A inhibitor with pan-genotype activity for
      treatment of HCV.
AB  - HCV NS5A inhibitors have shown impressive in vitro potency profiles in HCV
      replicon assays thus making them attractive components for inclusion in an all
      oral fixed dose combination regimen. Herein, we describe the discovery and
      characterization of silyl proline-containing HCV NS5A inhibitor MK-8325 with good
      pan-genotype activity and acceptable pharmacokinetic properties.

PMID- 29653895
TI  - An orally available, brain-penetrant CAMKK2 inhibitor reduces food intake in
      rodent model.
AB  - Hypothalamic CAMKK2 represents a potential mechanism for chemically affecting
      satiety and promoting weight loss in clinically obese patients. Single-digit
      nanomolar inhibitors of CAMKK2 were identified in three related ATP-competitive
      series. Limited optimization of kinase selectivity, solubility, and
      pharmacokinetic properties were undertaken on all three series, as SAR was often
      transferrable. Ultimately, a 2,4-diaryl 7-azaindole was optimized to afford a
      tool molecule that potently inhibits AMPK phosphorylation in a hypothalamus
      derived cell line, is orally bioavailable, and crosses the blood-brain barrier.
      When dosed orally in rodents, compound 4 t limited ghrelin-induced food intake.

PMID- 29653896
TI  - Insights from population health science to inform research on firearms.

PMID- 29653897
TI  - Tissue expansion in cranioplasty - a collaborative approach for all involved for
      improved outcomes.

PMID- 29653898
TI  - Denervation leads to volume regression in breast cancer.
AB  - The nervous system plays a key role in controlling the dynamic functions of
      multicellular complex organisms. Although peripheral nerves are supposed to play
      a pivotal role in tumor growth and dissemination, little experimental evidence
      exists to date. We assessed the effect of denervation on breast cancer growth by
      magnetic resonance imaging (MRI) in rats. Human breast cancer cells were
      implanted into adipofascial flaps with intact or surgically excised supplying
      nerve. Tumor volumes were measured 2 and 8 weeks after implantation by in vivo
      MRI. Results were validated by histology. Postoperative tumor volumes at 2 and 8
      weeks were reduced by 76% (95% CI: 22-93%) in the denervated groups. Tumor area
      as determined histologically was reduced by 70% (95% CI: 60-78%). Thus,
      peripheral denervation may be an effective surgical approach for the palliative
      treatment of locally progressing or uncontrollable breast cancer.

PMID- 29653899
TI  - Matrix Gla protein negatively regulates calcification of human aortic valve
      interstitial cells isolated from calcified aortic valves.
AB  - Calcified aortic valve stenosis (CAS) is a common heart valve disease in elderly
      people, and is mostly accompanied by ectopic valve calcification. We recently
      demonstrated that tumor necrosis factor-alpha (TNF-alpha) induces calcification
      of human aortic valve interstitial cells (HAVICs) obtained from CAS patients. In
      this study, we investigated the role of matrix Gla protein (MGP), a known
      calcification inhibitor that antagonizes bone morphogenetic protein 2 (BMP2) in
      TNF-alpha-induced calcification of HAVICs. HAVICs isolated from aortic valves
      were cultured, and calcification was significantly induced with 30 ng/mL TNF
      alpha. Gene expression of the calcigenic marker, BMP2, was significantly
      increased in response to TNF-alpha, while the gene and protein expression of MGP
      was strongly decreased. To confirm the role of MGP, MGP-knockdown HAVICs and
      HAVICs overexpressing MGP were generated. In HAVICs, in which MGP expression was
      inhibited by small interfering RNA, calcification and BMP2 gene expression were
      induced following long-term culture for 32 days in the absence of TNF-alpha. In
      contrast, HAVICs overexpressing MGP had significantly decreased TNF-alpha-induced
      calcification. These results suggest that MGP acts as a negative regulator of
      HAVIC calcification, and as such, may be helpful in the development of new
      therapies for ectopic calcification of the aortic valve.

PMID- 29653900
TI  - Use of in-home stationary cycling equipment among parents in a family-based
      randomized trial intervention.
AB  - OBJECTIVES: The purpose of this study was to examine the use of home exercise
      equipment in the form of exergame cycling compared to a stationary recumbent
      bicycle ergometer in front of TV in the home over 3 months among parents of an
      intervention with their inactive children. The primary outcome was bike use
      (total weekly duration). Predictors of bike use in the form of theory of planned
      behavior and self-determination theory were also examined. DESIGN: Randomized
      controlled trial. METHOD: Sixty eight parents of children aged 10-14 were
      randomized to either the exergame condition (n=36) or the standard bike condition
      (n=32). Weekly bike use was recorded in a log-book. RESULTS: The exergame bike
      and a standard bike in front of a TV had similar use across three months (p=.13,
      etap2=.02), which declined over time (p<.01, etap2=.14). Parents who were active
      at baseline and had the intention to use the bikes were more likely to use the
      bikes (p<.05). Furthermore, those who reported higher perceived control,
      intrinsic motivation, and affective attitude were more likely to use the bikes
      (p<.05). CONCLUSIONS: The findings suggested that irrespective of modality, use
      of exercise equipment declined considerably for parents over three-months.
      Parents may also benefit from family physical activity interventions, but it
      depends on their physical activity status, how much they would enjoy using the
      equipment, and their overall perceived control over being physically active.
      TRIAL REGISTRATION: clinicaltrials.gov #NCT01373762. Registered 1 June 2011.

PMID- 29653901
TI  - Hospital and Institutionalisation Care Costs after Limb and Visceral Ischaemia
      Benchmarked Against Stroke: Long-Term Results of a Population Based Cohort Study.
AB  - OBJECTIVE/BACKGROUND: There are few published data on the acute care or long-term
      costs after acute/critical limb or visceral ischaemia (ACLVI) events. Using data
      from patients with acute events in a population based incidence study (Oxford
      Vascular Study), the present study aimed to determine the long-term costs after
      an ACLVI event. METHODS: All patients with first ever incident ACLVI from 2002 to
      2012 were included. Analysis was based on follow up until January 2017, with all
      patients having full 5 year follow up. Multivariate regressions were used to
      assess baseline and subsequent predictors of total 5 year hospital care costs.
      Overall costs after an ACLVI event were benchmarked against those after stroke in
      the same population, during the same period. RESULTS: Among 351 patients with an
      ACLVI event, mean 5 year total care costs were ?35,211 (SD 50,500), of which
      ?6443 (18%) were due to long-term institutionalisation. Costs differed by type of
      event (acute visceral ischaemia ?16,476; acute limb ischaemia ?24,437; critical
      limb ischaemia ?46,281; p < 0.001). Results of the multivariate analyses showed
      that patients with diabetes and those undergoing above knee amputations incurred
      additional costs of ?11,804 (p = 0.014) and ?25,692 (p < 0.001), respectively.
      Five year hospital care costs after an ACLVI event were significantly higher than
      after stroke (?28,768 vs. ?22,623; p = 0.004), but similar after including long
      term costs of institutionalisation (?35,211 vs. ?35,391; p = 0.957). CONCLUSION:
      Long-term care costs after an ACLVI event are considerable, especially after
      critical limb ischaemia. Hospital care costs were significantly higher than for
      stroke over the long term, and were similar after inclusion of costs of
      institutionalisation.

PMID- 29653902
TI  - Diabetes mellitus, blood glucose and the risk of atrial fibrillation: A
      systematic review and meta-analysis of cohort studies.
AB  - BACKGROUND: Diabetes and elevated blood glucose have been associated with
      increased risk of atrial fibrillation in a number of epidemiological studies,
      however, the findings have not been entirely consistent. We conducted a
      systematic review and meta-analysis to clarify the association. MATERIAL AND
      METHODS: We searched the PubMed and Embase databases for studies of diabetes and
      blood glucose and atrial fibrillation up to July 18th 2017. Cohort studies were
      included if they reported relative risk (RR) estimates and 95% confidence
      intervals (CIs) of atrial fibrillation associated with a diabetes diagnosis,
      prediabetes or blood glucose. Summary RRs were estimated using a random effects
      model. RESULTS: Thirty four studies were included in the meta-analysis of
      diabetes, pre-diabetes or blood glucose and atrial fibrillation. Thirty two
      cohort studies (464,229 cases, >10,244,043 participants) were included in the
      analysis of diabetes mellitus and atrial fibrillation. The summary RR for
      patients with diabetes mellitus versus patients without diabetes was 1.30 (95%
      CIs: 1.03-1.66), however, there was extreme heterogeneity, I2 = 99.9%) and
      evidence of publication bias with Begg's test, p < 0.0001. After excluding a very
      large and outlying study the summary RR was 1.28 (95% CI: 1.22-1.35, I2 = 90%, n
      = 31, 249,772 cases, 10,244,043 participants). The heterogeneity was mainly due
      to differences in the size of the association between studies and the results
      persisted in a number of subgroup and sensitivity analyses. The summary RR was
      1.20 (95% CI: 1.03-1.39, I2 = 30%, n = 4, 2392 cases, 58,547 participants) for
      the association between prediabetes and atrial fibrillation. The summary RR was
      1.11 (95% CI: 1.04-1.18, I2 = 61%, n = 4) per 20 mg/dl increase of blood glucose
      in relation to atrial fibrillation (3385 cases, 247,447 participants) and there
      was no evidence of nonlinearity, pnonlinearity = 0.34. CONCLUSIONS: This meta
      analysis suggest that prediabetes and diabetes increase the risk of atrial
      fibrillation by 20% and 28%, respectively, and there is a dose-response
      relationship between increasing blood glucose and atrial fibrillation. Any
      further studies should clarify whether the association between diabetes and blood
      glucose and atrial fibrillation is independent of adiposity.

PMID- 29653903
TI  - Can RR intervals editing and selection techniques interfere with the analysis of
      heart rate variability?
AB  - BACKGROUND: Oscillation between successive sinus beats or RR intervals, termed
      heart rate variability, is an important marker of autonomic function of the
      heart. However, its analysis may be influenced by the database recorded based on
      the occurrence of interference. OBJECTIVE: To evaluate if the techniques of
      identification and editing of artifacts, as well as the selection methods of RR
      intervals, can interfere with heart rate variability analysis. METHODS: The RR
      intervals of 56 subjects (30 aortic stenosis patients, 14 physically active
      individuals, 12 amateur athletes) were recorded for 10min using a heart rate
      monitor. Values with differences greater than 20%, higher than three standard
      deviations or outside of the normal curve (95% confidence interval) were
      considered artifacts. These points were corrected through data replacement,
      adjacent, linear and polynomial interpolation, or excluded. Then, the 256 highest
      stability points and the last 5min of recordings were chosen. The software
      programs, Kubios HRV and GraphPAD, were used to calculate and to analyze the
      indices of heart rate variability, respectively. RESULTS: Strong agreement was
      observed among the identification algorithms; there was no difference between the
      correction techniques (p=0.95); and the selection methods exhibited different
      sections (p<0.01) with a direct influence on approximated entropy (p<0.05).
      CONCLUSION: With short-term recordings, selection methods may interfere with the
      non-linear heart rate variability analysis. The confidence interval, the
      replacement by the average of previous data and the selection of 256 of the
      highest stability points of the signal seem to be the most adequate procedures to
      treat the data with prior to analysis.

PMID- 29653906
TI  - Vocal Fold Motion Impairment.
AB  - Vocal fold motion abnormalities in children are the second most common form of
      laryngeal pathology seen in children, and often present in the first 24 months of
      life. A thorough evaluation of the aerodigestive tract will include an
      examination of the vocal folds, and a proper diagnosis is essential in order to
      decipher the etiology of swallowing, voicing and breathing abnormalities. This
      article reviews the workup, management options and clinical outcomes of
      unilateral and bilateral vocal fold motion impairment in the pediatric
      population.

PMID- 29653904
TI  - Hippocampal Network Modularity Is Associated With Relational Memory Dysfunction
      in Schizophrenia.
AB  - BACKGROUND: Functional dysconnectivity has been proposed as a major
      pathophysiological mechanism for cognitive dysfunction in schizophrenia. The
      hippocampus is a focal point of dysconnectivity in schizophrenia, with decreased
      hippocampal functional connectivity contributing to the marked memory deficits
      observed in patients. Normal memory function relies on the interaction of complex
      corticohippocampal networks. However, only recent technological advances have
      enabled the large-scale exploration of functional networks with accuracy and
      precision. METHODS: We investigated the modularity of hippocampal resting-state
      functional networks in a sample of 45 patients with schizophrenia spectrum
      disorders and 38 healthy control subjects. Modularity was calculated for two
      distinct functional networks: a core hippocampal-medial temporal lobe cortex
      network and an extended hippocampal-cortical network. As hippocampal function
      differs along its longitudinal axis, follow-up analyses examined anterior and
      posterior networks separately. To explore effects of resting network function on
      behavior, we tested associations between modularity and relational memory
      ability. Age, sex, handedness, and parental education were similar between
      groups. RESULTS: Network modularity was lower in schizophrenia patients,
      especially in the posterior hippocampal network. Schizophrenia patients also
      showed markedly lower relational memory ability compared with control subjects.
      We found a distinct brain-behavior relationship in schizophrenia that differed
      from control subjects by network and anterior/posterior division-while relational
      memory in control subjects was associated with anterior hippocampal-cortical
      modularity, schizophrenia patients showed an association with posterior
      hippocampal-medial temporal lobe cortex network modularity. CONCLUSIONS: Our
      findings support a model of abnormal resting-state corticohippocampal network
      coherence in schizophrenia, which may contribute to relational memory deficits.

PMID- 29653905
TI  - Identification of Lyme borreliae proteins promoting vertebrate host blood
      specific spirochete survival in Ixodes scapularis nymphs using artificial feeding
      chambers.
AB  - Lyme borreliosis, the most common vector-borne illness in Europe and the United
      States, is caused by spirochetes of the Borrelia burgdorferi sensu lato complex
      and transmitted by Ixodes ticks. In humans, the spirochetes disseminate from the
      tick bite site to multiple tissues, leading to serious clinical manifestations.
      The ability of spirochetes to survive in ticks during blood feeding is thought to
      be essential for Lyme borreliae to be transmitted to different vertebrate hosts.
      This ability is partly attributed to several B. burgdorferi proteins, including
      BBA52 and Lp6.6, which promote spirochete survival in nymphal ticks feeding on
      mice. One of the strategies to identify such proteins without using live animals
      is to feed B. burgdorferi-infected ticks on blood via artificial feeding
      chambers. In previous studies, ticks were only fed on bovine blood in the feeding
      chambers. In this study, we used this chamber model and showed that I. scapularis
      ticks will not only acquire bovine blood but human and quail blood as well. The
      latter two are the incidental host and an avian host of Lyme borreliae,
      respectively. We also investigated the roles that BBA52 and Lp6.6 play in
      promoting spirochete survival in nymphal ticks fed on human or quail blood. After
      feeding on human blood, spirochete burdens in ticks infected with an lp6.6
      deficient B. burgdorferi were significantly reduced, while bba52-deficient
      spirochete burdens in ticks remained unchanged, similar to the wild-type strain.
      No strain showed a change in spirochete burdens in ticks fed on quail blood.
      These results indicate that Lp6.6 plays a role for B. burgdorferi in nymphs fed
      on human but not quail blood. Such information also demonstrates that the
      artificial feeding chamber is a powerful tool to identify B. burgdorferi proteins
      that promote vertebrate host blood-specific spirochete survival in I. scapularis
      ticks.

PMID- 29653907
TI  - Phenotype variability and allelic heterogeneity in KMT2B-Associated disease.
AB  - BACKGROUND: Mutations in Lysine-Specific Histone Methyltransferase 2B gene
      (KMT2B) have been reported to be associated with complex early-onset dystonia.
      Almost all reported KMT2B mutations occurred de novo in the paternal germline or
      in the early development of the patient. We describe clinico-genetic features on
      four Japanese patients with novel de novo mutations and demonstrate the
      phenotypic spectrum of KMT2B mutations. METHODS: We performed genetic studies,
      including trio-based whole exome sequencing (WES), in a cohort of Japanese
      patients with a seemingly sporadic early-onset generalized combined dystonia.
      Potential effects by the identified nucleotide variations were evaluated
      biologically. Genotype-phenotype correlations were also investigated. RESULTS:
      Four patients had de novo heterozygous mutations in KMT2B, c.309delG, c.1656dupC,
      c.3325_3326insC, and c.5636delG. Biological analysis of KMT2B mRNA levels showed
      a reduced expression of mutant transcript frame. All patients presented with
      motor milestone delay, microcephaly, mild psychomotor impairment, childhood-onset
      generalized dystonia and superimposed choreoathetosis or myoclonus. One patient
      cannot stand due to axial hypotonia associated with cerebellar dysfunction. Three
      patients had bilateral globus pallidal deep brain stimulation (DBS) with
      excellent or partial response. CONCLUSIONS: We further demonstrate the allelic
      heterogeneity and phenotypic variations of KMT2B-associated disease.
      Haploinsufficiency is one of molecular pathomechanisms underlying the disease.
      Cardinal clinical features include combined dystonia accompanying mild
      psychomotor disability. Cerebellum would be affected in KMT2B-associated disease.

PMID- 29653908
TI  - Improving neurophysiological biomarkers for functional myoclonic movements.
AB  - INTRODUCTION: Differentiating between functional jerks (FJ) and organic myoclonus
      can be challenging. At present, the only advanced diagnostic biomarker to support
      FJ is the Bereitschaftspotential (BP). However, its sensitivity is limited and
      its evaluation subjective. Recently, event related desynchronisation in the broad
      beta range (13-45 Hz) prior to functional generalised axial (propriospinal)
      myoclonus was reported as a possible complementary diagnostic marker for FJ. Here
      we study the value of ERD together with a quantified BP in clinical practice.
      METHODS: Twenty-nine patients with FJ and 16 patients with cortical myoclonus
      (CM) were included. Jerk-locked back-averaging for determination of the
      'classical' and quantified BP, and time-frequency decomposition for the event
      related desynchronisation (ERD) were performed. Diagnostic gain, sensitivity and
      specificity were obtained for individual and combined techniques. RESULTS: We
      detected a classical BP in 14/29, a quantitative BP in 15/29 and an ERD in 18/29
      patients. At group level we demonstrate that ERD in the broad beta band preceding
      a jerk has significantly higher amplitude in FJ compared to CM (respectively 
      0.14 +/- 0.13 and +0.04 +/- 0.09 (p < 0.001)). Adding ERD to the classical BP
      achieved an additional diagnostic gain of 53%. Furthermore, when combining ERD
      with quantified and classical BP, an additional diagnostic gain of 71% was
      achieved without loss of specificity. CONCLUSION: Based on the current findings
      we propose to the use of combined beta ERD assessment and quantitative BP
      analyses in patients with a clinical suspicion for all types of FJ with a
      negative classical BP.

PMID- 29653909
TI  - Comprehensive identification of delusions and olfactory, tactile, gustatory, and
      minor hallucinations in Parkinson's disease psychosis.
AB  - INTRODUCTION: Psychotic symptoms are underdiagnosed in Parkinson's disease (PD),
      and there is a need for a comprehensive PD psychosis rating scale. METHODS: Cross
      sectional analysis of 199 consecutive PD outpatients. After a routine clinical
      visit that included the Unified Parkinson's Disease Rating Scale (UPDRS) and Non
      Motor Symptoms Questionnaire (NMS-Quest), subjects completed the enhanced Scale
      for the Assessment of Positive Symptoms in PD (eSAPS-PD), a structured clinical
      interview that included the standard SAPS-PD with additional prompts for
      delusions and olfactory, gustatory, and minor hallucinations. Based on the
      combined results of these assessments, subjects were categorized as having major
      psychotic symptoms (hallucinations or delusions; PDP-major), isolated minor
      psychotic symptoms (passage hallucinations, presence hallucinations, or
      illusions; PDP-minor), or no psychotic symptoms (PD-controls). RESULTS: We
      identified 58 subjects (29%) with psychotic symptoms, including 28 (14%) with
      major psychotic symptoms and 30 (15%) with isolated minor psychotic symptoms.
      Hallucinations were present in 56 subjects (28%); most commonly visual (24%, of
      which 21% were minor only), followed by olfactory (6%), tactile (4%), auditory
      (2%), and gustatory (1%). The eSAPS-PD detected psychotic symptoms in more
      subjects (n = 55, 28%) than all other assessments combined (clinical visit, UPDRS
      part 1, and NMS-Quest) (n = 22, 11%). Compared with PD-controls, PDP-minor
      subjects had a higher burden of other non-motor symptoms on the Non-Motor
      Symptoms Scale (37 [27-51] vs. 18 [9-36], p < 0.001) and lower quality of life
      scores on the PD Quality of Life Questionnaire (138 [125-151] vs. 149 [137-165],
      p = 0.01). CONCLUSION: The eSAPS-PD can markedly improve detection of psychotic
      symptoms in PD.

PMID- 29653910
TI  - Deep Brain Stimulation associated gliosis: A post-mortem study.
AB  - BACKGROUND: DBS is a well-established therapy for patients with PD and is an
      emerging therapy for other neuropsychiatric disorders. Despite the rise in DBS
      usage, relatively little is known about the tissue and cellular responses to DBS.
      PURPOSE: To examine post-mortem effects of DBS leads by objectively quantifying
      gliosis around the distal DBS lead tip. METHODS: The UF DBS Brain Bank repository
      currently has 64 brains, of which 18 cases met criteria for this study. RESULTS:
      The average patient age was 54.88 +/- 13.43 years (mean +/- SD), male:female
      ratio was 3:1, average disease duration was 20.70 +/- 6.36 years and average DBS
      duration was 7.26 +/- 6.36 years. Microscopic evaluation revealed tissue reaction
      and astrocytic responses to the lead. Significant fibrosis was seen in n = 2
      brains and prominent microglial response in n = 1. Mean gliotic collar measured
      from H&E and GFAP staining was 122.5 MUm and 162.5 MUm, respectively. Mean
      gliotic thickness at the DBS electrode lead tip was 119.13 +/- 64.29 MUm for
      patients receiving DBS for 0-5 years, 127.85 +/- 94.34 MUm for 5-10 years and
      111.73 +/- 114.18 MUm for patients with DBS >10 years. Kruskal-Wallis one-way
      analysis of variance (ANOVA) revealed no statistically significant differences
      between DBS duration and amount of gliosis. CONCLUSIONS: This study revealed that
      approximately three out of four post-mortem DBS cases exhibited pathological
      evidence of a glial collar or scar present at the ventral DBS lead tip. The
      amount of gliosis was not significantly associated with duration of DBS. Future
      studies should include serial sectioning across all DBS contacts with correlation
      to the volume of tissue activation and to the clinical outcome.

PMID- 29653911
TI  - Criteria for diagnosis and postoperative control of acromegaly, and screening and
      management of its comorbidities: Expert consensus.
AB  - Acromegaly is a rare disease with many comorbidities that impair quality of life
      and limit survival. There are discrepancies in various clinical guidelines
      regarding diagnosis and postoperative control criteria, as well as screening and
      optimal management of comorbidities. This expert consensus was aimed at
      establishing specific recommendations for the Spanish healthcare system. The
      existing recommendations, the scientific evidence on which they are based, and
      the main controversies are reviewed. Unfortunately, the low prevalence and high
      clinical variability of acromegaly do not provide strong scientific evidences. To
      mitigate this disadvantage, a modified Delphi questionnaire, combining the best
      available scientific evidence with the collective judgment of experts, was used.
      The questionnaire, generated after a face-to-face debate, was completed by 17
      Spanish endocrinologists expert in acromegaly. A high degree of consensus was
      reached (79.3%), as 65 of the total 82 statements raised were accepted. Some
      criteria for diagnosis and postoperative control were identified by this
      procedure. Regarding comorbidities, recommendations have been established or
      suggested for screening and management of oncological, cardiovascular,
      respiratory (sleep apnea), metabolic (dyslipidemia and diabetes),
      musculoskeletal, and hypopituitarism-related disorders. Consensus recommendations
      may facilitate and homogenize clinical care to patients with acromegaly in the
      Spanish health system.

PMID- 29653912
TI  - Complete heterotopic pancreas.

PMID- 29653913
TI  - Penile Prosthesis Implantation in Patients With Peyronie's Disease: Results of
      the PROPPER Study Demonstrates a Decrease in Patient-Reported Depression.
AB  - BACKGROUND: Although there is a strong correlation between erectile dysfunction
      and Peyronie's disease (PD), there are limited data on the efficacy and
      satisfaction of inflatable penile prosthesis (IPP) placement in this population.
      AIM: To assess the efficacy and overall satisfaction of IPP placement in men with
      erectile dysfunction and concomitant PD using the Prospective Registry of
      Outcomes with Penile Prosthesis for Erectile Restoration (PROPPER). METHODS: Data
      from the PROPPER study were examined to determine patient baseline
      characteristics and primary and secondary etiologies before IPP treatment and
      included type and size of implant received, presence of corporal fibrosis, and
      operative time. Men completed 5 validated questionnaires at baseline and annually
      out to 5 years. OUTCOMES: IPP placement was performed in 250 patients with PD
      with comparable surgical times and outcomes as in patients without PD. RESULTS:
      1,180 men underwent IPP insertion at 11 sites; of these, 250 (21.2%) were
      diagnosed with PD. This is an ongoing study; 1- and 2-year data are available for
      177 (70.8%) and 130 (52.0%) patients, respectively. Intraoperatively, 51.2%
      patients with PD had corporal fibrosis, with an average operative time of 52.8
      minutes. At baseline, 19.3% of men (36 of 187) with PD reported being depressed,
      with a decrease to 10.5% (6 of 57; P = .02) and 10.9% (5 of 46; P = .07) at 1-
      and 2-year follow-ups, respectively. More than 80% of patients with PD were
      satisfied or very satisfied at 1- and 2-year follow-ups. In addition, more than
      88% of patients with PD were using their device at the 1- and 2-year follow-up
      visits. CLINICAL IMPLICATIONS: Patients with concomitant PD and erectile
      dysfunction can safely and effectively have an IPP placed with similar outcomes
      as patients without PD. STRENGTHS AND LIMITATIONS: The 1st limitation was that
      all participating prosthetic urologists were high-volume implanters and these
      results might not be representative of those of general urologists. A 2nd
      limitation was that none of the patients were randomized. A 3rd limitation was
      that although most study points were mandatory, some of the data collection,
      including depression data, was optional, with not all sites participating. A 4th
      limitation was that depression data were self-reported. CONCLUSION: IPP can be
      inserted in patients with PD with acceptable patient satisfaction and usage and
      depressive symptoms appear to lessen in patients with PD after IPP placement.
      Khera M, Bella A, Karpman E, et al. Penile Prosthesis Implantation in Patients
      With Peyronie's Disease: Results of the PROPPER Study Demonstrates a Decrease in
      Patient-Reported Depression. J Sex Med 2018;15:786-788.

PMID- 29653914
TI  - Culture and Sexuality: Cognitive-Emotional Determinants of Sexual Dissatisfaction
      Among Iranian and New Zealand Women.
AB  - BACKGROUND: Several studies have demonstrated that culture plays a fundamental
      role in individuals' beliefs, attitudes, and values toward sexuality, and
      influences their ability to enjoy sex. It follows that culture may influence
      sexual satisfaction or dissatisfaction. AIM: To examine and compare cognitive
      emotional variables related to women's sexual dissatisfaction in Iran and New
      Zealand. METHODS: In total, 196 Iranian women and 207 New Zealand women
      participated in the study, answering questionnaires evaluating dysfunctional
      sexual beliefs, automatic thoughts, emotional and sexual response during sexual
      activity, as well as sexual satisfaction. OUTCOMES: Sexual beliefs were measured
      by the Sexual Dysfunctional Beliefs Questionnaire, thoughts and emotional
      responses were measured by the Sexual Modes Questionnaire, and sexual
      satisfaction was measured by the Sexual Satisfaction Index. RESULTS: Findings
      indicated that in both Iranian and New Zealand women, failure and disengagement
      thoughts, lack of erotic thoughts, and emotions of fear during sexual activity
      were significant predictors of sexual dissatisfaction. Besides these common
      predictors, results also indicated that sexual conservatism and women's sexual
      passivity beliefs, sexual abuse thoughts, and fear during sexual activity were
      significant predictors of sexual dissatisfaction in Iranian women. Beliefs of
      sexual desire and pleasure as a sin; age-related beliefs; and emotions such as
      sadness, disillusion, and hurt were significant predictors of sexual
      dissatisfaction in New Zealand women. CLINICAL TRANSLATION: The present findings
      could facilitate a better understanding of cultural differences in the roles
      played by dysfunctional sexual beliefs, negative automatic thoughts, and negative
      emotions during sexual activity, and the value of these beliefs, thoughts, and
      emotions in predicting sexual dissatisfaction. CONCLUSIONS: The strength of this
      study is in providing an examination of the role of culturally bound beliefs in
      predicting sexual dissatisfaction in women from different cultural backgrounds.
      Limitations include the lack of evaluation of psychological and interpersonal
      variables that may impact on women's sexual dissatisfaction. These findings
      suggest that there may be a role of culture in shaping beliefs, attitudes, and
      values toward sexuality; and provide evidence for the effect of cognitive
      emotional variables in predicting women's sexual dissatisfaction. Abdolmanafi A,
      Nobre P, Winter S, et al. Culture and Sexuality: Cognitive-Emotional Determinants
      of Sexual Dissatisfaction Among Iranian and New Zealand Women. J Sex Med
      2018;15:687-697.

PMID- 29653916
TI  - Nutritional support to reduce mortality in patients with HIV?

PMID- 29653917
TI  - Privacy-Preserving Patient Similarity Learning in a Federated Environment:
      Development and Analysis.
AB  - BACKGROUND: There is an urgent need for the development of global analytic
      frameworks that can perform analyses in a privacy-preserving federated
      environment across multiple institutions without privacy leakage. A few studies
      on the topic of federated medical analysis have been conducted recently with the
      focus on several algorithms. However, none of them have solved similar patient
      matching, which is useful for applications such as cohort construction for cross
      institution observational studies, disease surveillance, and clinical trials
      recruitment. OBJECTIVE: The aim of this study was to present a privacy-preserving
      platform in a federated setting for patient similarity learning across
      institutions. Without sharing patient-level information, our model can find
      similar patients from one hospital to another. METHODS: We proposed a federated
      patient hashing framework and developed a novel algorithm to learn context
      specific hash codes to represent patients across institutions. The similarities
      between patients can be efficiently computed using the resulting hash codes of
      corresponding patients. To avoid security attack from reverse engineering on the
      model, we applied homomorphic encryption to patient similarity search in a
      federated setting. RESULTS: We used sequential medical events extracted from the
      Multiparameter Intelligent Monitoring in Intensive Care-III database to evaluate
      the proposed algorithm in predicting the incidence of five diseases
      independently. Our algorithm achieved averaged area under the curves of 0.9154
      and 0.8012 with balanced and imbalanced data, respectively, in kappa-nearest
      neighbor with kappa=3. We also confirmed privacy preservation in similarity
      search by using homomorphic encryption. CONCLUSIONS: The proposed algorithm can
      help search similar patients across institutions effectively to support federated
      data analysis in a privacy-preserving manner.

PMID- 29653919
TI  - Social Interaction Needs and Entertainment Approaches to Pregnancy Well-Being in
      mHealth Technology Design for Low-Income Transmigrant Women: Qualitative Codesign
      Study.
AB  - BACKGROUND: Low-income Caribbean transmigrant women face unique health challenges
      during pregnancy that set forth multidimensional implications for the design of
      mobile health (mHealth). Acknowledgment of the unique health needs of low-income
      Caribbean immigrant women in the United States and what that entails regarding
      technology design remains rarely examined in the literature of mHealth
      technologies. OBJECTIVE: The goal of this study was to reveal the needs and gaps
      in mHealth interventions for pregnant immigrant women not yet realized in this
      field. These understandings reveal design opportunities for mHealth. METHODS: The
      use of the qualitative participatory action research approach of codesign
      workshops in this study resulted in design solutions by the participants after
      reflecting on their earlier focus group discussions. The highlights are not the
      resulting designs per se but rather the inferences derived from the researcher
      reflecting on these designs. RESULTS: The designs exposed two themes relevant to
      this paper. First, the participants desired the inclusion and rebuilding of
      social and organizational relationships in mHealth. The resulting designs
      formulate an understanding of the women's health-related social support needs and
      how technology can facilitate them. Second, the participants wanted entertainment
      with an element of social participation incorporated in mHealth pregnancy
      management interventions. This brings attention to the role entertainment can add
      to the impact mHealth can deliver for pregnancy well-being. CONCLUSIONS: The
      study concluded with an examination of social and entertainment design
      implications that reveal pregnant immigrant women's virtual health-related
      sharing habits, choice of sharing interaction scenarios during pregnancy (eg,
      local, long distance, one-way, two-way, and many-many), and choice of sharing
      media (eg, text, voice, and video). Additionally, the study revealed exclusions
      to social sharing capabilities in health technologies for these women.

PMID- 29653918
TI  - Use of Smartphones for Early Detection of Melanoma: Systematic Review.
AB  - BACKGROUND: The early diagnosis of melanoma is associated with decreased
      mortality. The smartphone, with its apps and the possibility of sending
      photographs to a dermatologist, could improve the early diagnosis of melanoma.
      OBJECTIVE: The aim of our review was to report the evidence on (1) the diagnostic
      performance of automated smartphone apps and store-and-forward teledermatology
      via a smartphone in the early detection of melanoma, (2) the impact on the
      patient's medical-care course, and (3) the feasibility criteria (focusing on the
      modalities of picture taking, transfer of data, and time to get a reply).
      METHODS: We conducted a systematic search of PubMed for the period from January
      1, 2007 (launch of the first smartphone) to November 1, 2017. RESULTS: The
      results of the 25 studies included 13 concentrated on store-and-forward
      teledermatology, and 12 analyzed automated smartphone apps. Store-and-forward
      teledermatology opens several new perspectives, such as it accelerates the care
      course (less than 10 days vs 80 days), and the related procedures were assessed
      in primary care populations. However, the concordance between the conclusion of a
      teledermatologist and the conclusion of a dermatologist who conducts a face-to
      face examination depended on the study (the kappa coefficient range was .20 to
      .84, median kappa=.60). The use of a dermoscope may improve the concordance (the
      kappa coefficient range was .29 to .87, median kappa=.74). Regarding automated
      smartphone apps, the major concerns are the lack of assessment in clinical
      practice conditions, the lack of assessment in primary care populations, and
      their low sensitivity, ranging from 7% to 87% (median 69%). In this literature
      review, up to 20% of the photographs transmitted were of insufficient quality.
      The modalities of picture taking and encryption of the data were only partially
      reported. CONCLUSIONS: The use of store-and-forward teledermatology could improve
      access to a dermatology consultation by optimizing the care course. Our review
      confirmed the absence of evidence of the safety and efficacy of automated
      smartphone medical apps. Further research is required to determine quality
      criteria, as there was major variability among the studies.

PMID- 29653915
TI  - Effect of ready-to-use supplementary food on mortality in severely
      immunocompromised HIV-infected individuals in Africa initiating antiretroviral
      therapy (REALITY): an open-label, parallel-group, randomised controlled trial.
AB  - BACKGROUND: In sub-Saharan Africa, severely immunocompromised HIV-infected
      individuals have a high risk of mortality during the first few months after
      starting antiretroviral therapy (ART). We hypothesise that universally providing
      ready-to-use supplementary food (RUSF) would increase early weight gain, thereby
      reducing early mortality compared with current guidelines recommending ready-to
      use therapeutic food (RUTF) for severely malnourished individuals only. METHODS:
      We did a 2 * 2 * 2 factorial, open-label, parallel-group trial at inpatient and
      outpatient facilities in eight urban or periurban regional hospitals in Kenya,
      Malawi, Uganda, and Zimbabwe. Eligible participants were ART-naive adults and
      children aged at least 5 years with confirmed HIV infection and a CD4 cell count
      of fewer than 100 cells per MUL, who were initiating ART at the facilities. We
      randomly assigned participants (1:1) to initiate ART either with (RUSF) or
      without (no-RUSF) 12 weeks' of peanut-based RUSF containing 1000 kcal per day and
      micronutrients, given as two 92 g packets per day for adults and one packet (500
      kcal per day) for children aged 5-12 years, regardless of nutritional status. In
      both groups, individuals received supplementation with RUTF only when severely
      malnourished (ie, body-mass index [BMI] <16-18 kg/m2 or BMI-for-age Z scores <-3
      for children). We did the randomisation with computer-generated, sequentially
      numbered tables with different block sizes incorporated within an online
      database. Randomisation was stratified by centre, age, and two other factorial
      randomisations, to 12 week adjunctive raltegravir and enhanced anti-infection
      prophylaxis (reported elsewhere). Clinic visits were scheduled at weeks 2, 4, 8,
      12, 18, 24, 36, and 48, and included nurse assessment of vital status and
      symptoms and dispensing of all medication including ART and RUSF. The primary
      outcome was mortality at week 24, analysed by intention to treat. Secondary
      outcomes included absolute changes in weight, BMI, and mid-upper-arm
      circumference (MUAC). Safety was analysed in all randomly assigned participants.
      Follow-up was 48 weeks. This trial is registered with ClinicalTrials.gov
      (NCT01825031) and the ISRCTN registry (43622374). FINDINGS: Between June 18,
      2013, and April 10, 2015, we randomly assigned 1805 participants to treatment:
      897 to RUSF and 908 to no-RUSF. 56 (3%) were lost-to-follow-up. 96 (10.9%, 95% CI
      9.0-13.1) participants allocated to RUSF and 92 (10.3%, 8.5-12.5) to no-RUSF died
      within 24 weeks (hazard ratio 1.05, 95% CI 0.79-1.40; log-rank p=0.75), with no
      evidence of interaction with the other randomisations (both p>0.7). Through 48
      weeks, adults and adolescents aged 13 years and older in the RUSF group had
      significantly greater gains in weight, BMI, and MUAC than the no-RUSF group
      (p=0.004, 0.004, and 0.03, respectively). The most common type of serious adverse
      event was specific infections, occurring in 90 (10%) of 897 participants assigned
      RUSF and 87 (10%) of 908 assigned no-RUSF. By week 48, 205 participants had
      serious adverse events in both groups (p=0.81), and 181 had grade 4 adverse
      events in the RUSF group compared with 172 in the non-RUSF group (p=0.45).
      INTERPRETATION: In severely immunocompromised HIV-infected individuals, providing
      RUSF universally at ART initiation, compared with providing RUTF to severely
      malnourished individuals only, improved short-term weight gain but not mortality.
      A change in policy to provide nutritional supplementation to all severely
      immunocompromised HIV-infected individuals starting ART is therefore not
      warranted at present. FUNDING: Joint Global Health Trials Scheme (UK Medical
      Research Council, UK Department for International Development, and Wellcome
      Trust).

PMID- 29653920
TI  - Development of a Web-based Family Intervention for BRCA Carriers and Their
      Biological Relatives: Acceptability, Feasibility, and Usability Study.
AB  - BACKGROUND: Carriers of breast cancer gene (BRCA) mutations are asked to
      communicate genetic test results to their biological relatives to increase
      awareness of cancer risk and promote use of genetic services. This process is
      highly variable from family to family. Interventions that support communication
      of genetic test results, coping, and offer decision support in families harboring
      a pathogenic variant may contribute to effective management of hereditary cancer.
      OBJECTIVE: The aim of this paper was to describe the development of the Family
      Gene Toolkit, a Web-based intervention targeting BRCA carriers and untested blood
      relatives, designed to enhance coping, family communication, and decision making.
      METHODS: We present findings from focus groups regarding intervention
      acceptability and participant satisfaction and from a pre-post pilot study with
      random allocation to a wait-listed control group regarding intervention
      feasibility and usability. RESULTS: The Family Gene Toolkit was developed by a
      multidisciplinary team as a psycho-educational and skills-building intervention.
      It includes two live webinar sessions and a follow-up phone call guided by a
      certified genetic counselor and a master's prepared oncology nurse. Each live
      webinar includes two modules (total four modules) presenting information about
      BRCA mutations, a decision aid for genetic testing, and two skill-building
      modules for effective coping and family communication. Participants in focus
      groups (n=11) were highly satisfied with the intervention, reporting it to be
      useful and describing clearly the important issues. From the 12 dyads recruited
      in the pre-post pilot study (response rate 12/52, 23%), completion rate was 71%
      (10/14) for intervention and 40% (4/10) for wait-listed control groups.
      CONCLUSIONS: Acceptability and satisfaction with the Family Gene Toolkit is high.
      On the basis of the findings from usability and feasibility testing,
      modifications on timing, delivery mode, and recruitment methods have been
      implemented. TRIAL REGISTRATION: ClinicalTrials.gov NCT02154633;
      https://clinicaltrials.gov/ct2/show/NCT02154633 (Archived by WebCite at
      http://www.webcitation.org/6yYNvLPjv).

PMID- 29653921
TI  - Comparing a Mobile Decision Support System Versus the Use of Printed Materials
      for the Implementation of an Evidence-Based Recommendation: Protocol for a
      Qualitative Evaluation.
AB  - BACKGROUND: The distribution of printed materials is the most frequently used
      strategy to disseminate and implement clinical practice guidelines, although
      several studies have shown that the effectiveness of this approach is modest at
      best. Nevertheless, there is insufficient evidence to support the use of other
      strategies. Recent research has shown that the use of computerized decision
      support presents a promising approach to address some aspects of this problem.
      OBJECTIVE: The aim of this study is to provide qualitative evidence on the
      potential effect of mobile decision support systems to facilitate the
      implementation of evidence-based recommendations included in clinical practice
      guidelines. METHODS: We will conduct a qualitative study with two arms to compare
      the experience of primary care physicians while they try to implement an evidence
      based recommendation in their clinical practice. In the first arm, we will
      provide participants with a printout of the guideline article containing the
      recommendation, while in the second arm, we will provide participants with a
      mobile app developed after formalizing the recommendation text into a clinical
      algorithm. Data will be collected using semistructured and open interviews to
      explore aspects of behavioral change and technology acceptance involved in the
      implementation process. The analysis will be comprised of two phases. During the
      first phase, we will conduct a template analysis to identify barriers and
      facilitators in each scenario. Then, during the second phase, we will contrast
      the findings from each arm to propose hypotheses about the potential impact of
      the system. RESULTS: We have formalized the narrative in the recommendation into
      a clinical algorithm and have developed a mobile app. Data collection is expected
      to occur during 2018, with the first phase of analysis running in parallel. The
      second phase is scheduled to conclude in July 2019. CONCLUSIONS: Our study will
      further the understanding of the role of mobile decision support systems in the
      implementation of clinical practice guidelines. Furthermore, we will provide
      qualitative evidence to aid decisions made by low- and middle-income countries'
      ministries of health about investments in these technologies.

PMID- 29653922
TI  - Agile Acceptance Test-Driven Development of Clinical Decision Support Advisories:
      Feasibility of Using Open Source Software.
AB  - BACKGROUND: Moving to electronic health records (EHRs) confers substantial
      benefits but risks unintended consequences. Modern EHRs consist of complex
      software code with extensive local configurability options, which can introduce
      defects. Defects in clinical decision support (CDS) tools are surprisingly
      common. Feasible approaches to prevent and detect defects in EHR configuration,
      including CDS tools, are needed. In complex software systems, use of test-driven
      development and automated regression testing promotes reliability. Test-driven
      development encourages modular, testable design and expanding regression test
      coverage. Automated regression test suites improve software quality, providing a
      "safety net" for future software modifications. Each automated acceptance test
      serves multiple purposes, as requirements (prior to build), acceptance testing
      (on completion of build), regression testing (once live), and "living" design
      documentation. Rapid-cycle development or "agile" methods are being successfully
      applied to CDS development. The agile practice of automated test-driven
      development is not widely adopted, perhaps because most EHR software code is
      vendor-developed. However, key CDS advisory configuration design decisions and
      rules stored in the EHR may prove amenable to automated testing as "executable
      requirements." OBJECTIVE: We aimed to establish feasibility of acceptance test
      driven development of clinical decision support advisories in a commonly used
      EHR, using an open source automated acceptance testing framework (FitNesse).
      METHODS: Acceptance tests were initially constructed as spreadsheet tables to
      facilitate clinical review. Each table specified one aspect of the CDS advisory's
      expected behavior. Table contents were then imported into a test suite in
      FitNesse, which queried the EHR database to automate testing. Tests and
      corresponding CDS configuration were migrated together from the development
      environment to production, with tests becoming part of the production regression
      test suite. RESULTS: We used test-driven development to construct a new CDS tool
      advising Emergency Department nurses to perform a swallowing assessment prior to
      administering oral medication to a patient with suspected stroke. Test tables
      specified desired behavior for (1) applicable clinical settings, (2) triggering
      action, (3) rule logic, (4) user interface, and (5) system actions in response to
      user input. Automated test suite results for the "executable requirements" are
      shown prior to building the CDS alert, during build, and after successful build.
      CONCLUSIONS: Automated acceptance test-driven development and continuous
      regression testing of CDS configuration in a commercial EHR proves feasible with
      open source software. Automated test-driven development offers one potential
      contribution to achieving high-reliability EHR configuration. Vetting acceptance
      tests with clinicians elicits their input on crucial configuration details early
      during initial CDS design and iteratively during rapid-cycle optimization.

PMID- 29653925
TI  - What is the cost of palliative care in the UK? A systematic review.
AB  - OBJECTIVES: Little is known about the cost of a palliative care approach in the
      UK, and there is an absence of robust activity and unit cost data. The aim of
      this study was to review evidence on the costs of specialist and generalist
      palliative care in the UK, and to explore different approaches used for capturing
      activity and unit cost data. METHODS: A systematic review with narrative
      synthesis. Four electronic databases were searched for empirical literature on
      the costs of a palliative care approach in the UK, and a narrative method was
      used to synthesise the data. RESULTS: Ten papers met our inclusion criteria. The
      studies displayed significant variation in their estimates of the cost of
      palliative care, therefore it was not possible to present an accurate aggregate
      cost of palliative care in the UK. The majority of studies explored costs from a
      National Health Service perspective and only two studies included informal care
      costs. Approaches to estimating activity and costs varied. Particular challenges
      were noted with capturing activity and cost data for hospice and informal care.
      CONCLUSION: The data are limited, and the heterogeneity is such that it is not
      possible to provide an aggregate cost of palliative care in the UK. It is notable
      that the costs of hospice care and informal care are often neglected in economic
      studies. Further work is needed to address methodological and practical
      challenges in order to gain a more complete understanding of the costs of
      palliative care.

PMID- 29653924
TI  - Mitotic Exit Dysfunction through the Deregulation of APC/C Characterizes
      Cisplatin-Resistant State in Epithelial Ovarian Cancer.
AB  - Purpose: Acquired resistance to cisplatin is a major barrier to success in
      treatment of various cancers, and understanding mitotic mechanisms unique to
      cisplatin-resistant cancer cells can provide the basis for developing novel
      mitotic targeted therapies aimed at eradicating these cells.Experimental Design:
      Using cisplatin-resistant models derived from primary patient epithelial ovarian
      cancer (EOC) cells, we have explored the status of mitotic exit mechanisms in
      cisplatin-resistant cells.Results: We have uncovered an unexpected role of long
      term cisplatin treatment in inducing mitotic exit vulnerability characterized by
      increased spindle checkpoint activity and functional dependency on Polo-like
      kinase 1 (PLK1) for mitotic exit in the presence of anaphase promoting
      complex/cyclosome (APC/C) dysfunction in a cisplatin-resistant state.
      Accordingly, PLK1 inhibition decreased the survival of cisplatin-resistant cells
      in vitro and in vivo and exacerbated spindle checkpoint response in these cells.
      APC/CCDC20 inhibition increased sensitivity to pharmacologic PLK1 inhibition,
      further confirming the existence of APC/C dysfunction in cisplatin-resistant
      cells. In addition, we uncovered that resistance to volasertib, PLK1 inhibitor,
      is due to maintenance of cells with low PLK1 expression. Accordingly, stable PLK1
      downregulation in cisplatin-resistant cells induced tolerance to
      volasertib.Conclusions: We provide the first evidence of APC/C dysfunction in
      cisplatin-resistant state, suggesting that understanding APC/C functions in
      cisplatin-resistant state could provide a basis for developing novel mitotic exit
      based therapies to eradicate cisplatin-resistant cancer cells. Our results also
      show that PLK1 downregulation could underlie emergence of resistance to PLK1
      targeted therapies in cancers. Clin Cancer Res; 24(18); 4588-601. (c)2018 AACR.

PMID- 29653928
TI  - Response to: Can ultrasound of the major salivary glands assess histopathological
      changes induced by treatment with rituximab in primary Sjogren's syndrome?

PMID- 29653926
TI  - Inhibiting Fibronectin Attenuates Fibrosis and Improves Cardiac Function in a
      Model of Heart Failure.
AB  - BACKGROUND: Fibronectin (FN) polymerization is necessary for collagen matrix
      deposition and is a key contributor to increased abundance of cardiac
      myofibroblasts (MFs) after cardiac injury. We hypothesized that interfering with
      FN polymerization or its genetic ablation in fibroblasts would attenuate MF and
      fibrosis and improve cardiac function after ischemia/reperfusion (I/R) injury.
      METHODS: Mouse and human MFs were used to assess the impact of the FN
      polymerization inhibitor (pUR4) in attenuating pathological cellular features
      such as proliferation, migration, extracellular matrix deposition, and associated
      mechanisms. To evaluate the therapeutic potential of inhibiting FN polymerization
      in vivo, wild-type mice received daily intraperitoneal injections of either pUR4
      or control peptide (III-11C) immediately after cardiac surgery for 7 consecutive
      days. Mice were analyzed 7 days after I/R to assess MF markers and inflammatory
      cell infiltration or 4 weeks after I/R to evaluate long-term effects of FN
      inhibition on cardiac function and fibrosis. Furthermore, inducible, fibroblast
      restricted, FN gene-ablated (Tcf21MerCreMer; Fnflox) mice were used to evaluate
      cell specificity of FN expression and polymerization in the heart. RESULTS: pUR4
      administration on activated MFs reduced FN and collagen deposition into the
      extracellular matrix and attenuated cell proliferation, likely mediated through
      decreased c-myc signaling. pUR4 also ameliorated fibroblast migration accompanied
      by increased beta1 integrin internalization and reduced levels of phosphorylated
      focal adhesion kinase protein. In vivo, daily administration of pUR4 for 7 days
      after I/R significantly reduced MF markers and neutrophil infiltration. This
      treatment regimen also significantly attenuated myocardial dysfunction,
      pathological cardiac remodeling, and fibrosis up to 4 weeks after I/R. Last,
      inducible ablation of FN in fibroblasts after I/R resulted in significant
      functional cardioprotection with reduced hypertrophy and fibrosis. The addition
      of pUR4 to the FN-ablated mice did not confer further cardioprotection,
      suggesting that the salutary effects of inhibiting FN polymerization may be
      mediated largely through effects on FN secreted from the cardiac fibroblast
      lineage. CONCLUSIONS: Inhibiting FN polymerization or cardiac fibroblast gene
      expression attenuates pathological properties of MFs in vitro and ameliorates
      adverse cardiac remodeling and fibrosis in an in vivo model of heart failure.
      Interfering with FN polymerization may be a new therapeutic strategy for treating
      cardiac fibrosis and heart failure.

PMID- 29653927
TI  - Racial/ethnic variation and risk factors for allopurinol-associated severe
      cutaneous adverse reactions: a cohort study.
AB  - OBJECTIVES: To examine associations of race/ethnicity and purported risk factors
      with hospitalised allopurinol-associated severe cutaneous adverse reactions
      (AASCARs). METHODS: We used US Medicaid data to identify incident allopurinol
      users between 1999 and 2012. We examined the risk of hospitalised AASCARs
      according to race/ethnicity and purported key risk factors and calculated
      relative risks (RR). RESULTS: Among 400 401 allopurinol initiators, we documented
      203 hospitalised AASCAR cases (1 in 1972 initiators). The average AASCAR
      hospitalisation was 9.6 days and 43 individuals (21%) died. The multivariable
      adjusted RRs for AASCARs among blacks, Asians and Native Hawaiians/Pacific
      Islanders compared with whites or Hispanics were 3.00 (95% CI 2.18 to 4.14), 3.03
      (95% CI 1.72 to 5.34) and 6.68 (95% CI 4.37 to 10.22), respectively. Female sex,
      older age (>=60 years), chronic kidney disease and initial allopurinol dose (>100
      mg/day) were independently associated with a 2.5-fold, 1.7-fold, 2.3-fold and 1.9
      fold higher risk of AASCAR, respectively. In our combined demographic analysis,
      older women (>=60 years) of a high-risk race/ethnicity (blacks, Asians or Native
      Hawaiians/Pacific Islanders) had over a 12-fold higher risk of hospitalised
      AASCARs than younger men of a low-risk race/ethnicity (whites or Hispanics)
      (multivariable-adjusted RR, 12.25; 95% CI 6.46 to 23.25). CONCLUSIONS: This
      racially diverse (yet mostly white) cohort study indicates that the risk of
      hospitalised AASCAR is rare overall, although blacks, Asians and Native
      Hawaiians/Pacific-Islanders have a substantially higher risk of hospitalised
      AASCARs, particularly among older women. These data also support the practice of
      initiating allopurinol at a low dose (eg, <=100 mg/day).

PMID- 29653929
TI  - Imaging Insights on the Aorta in Aging.
AB  - The aorta has 2 main functions, conduit and cushion, and is designed to transmit
      blood to the periphery and buffer pulsatile stress from ventricular contraction.
      In the interaction between the structural and functional changes of the aorta,
      aging and disease processes impact on aortic material properties and
      hemodynamics. For a comprehensive assessment of changes in aortic structure and
      function associated with aging and disease, noninvasive cardiovascular imaging
      techniques, especially magnetic resonance imaging, have recently been developed.
      Magnetic resonance imaging allows for direct and accurate measurement of
      different aortic characteristics including structural measures such as aortic
      area or volume, aortic length, curvature, and aortic wall thickness and
      functional measures such as aortic strain, distensibility, and pulse wave
      velocity. Excellent reproducibility of magnetic resonance imaging methods allows
      us to assess the response of the whole aorta to both pharmacological and
      nonpharmacological therapies. Aortic flow and functional assessment could be
      added to clinical routine cardiac magnetic resonance as a comprehensive imaging
      modality primarily performed for the noninvasive evaluation of left ventricular
      function, left ventricular load, and vascular/ventricular coupling. New
      techniques such as 4-dimensional flow could provide and further elucidate the
      combined age-related effects of altered aortic geometry and function. This
      following review will describe the pathophysiological aspects of the aorta and
      the ability, value, and prospects of cardiovascular imaging, especially magnetic
      resonance imaging, to study age-related changes in aortic structure and function
      and assess the relationship between these alterations and cardiovascular disease.

PMID- 29653931
TI  - The Future of Circulation: Cardiovascular Imaging: Expanding Our Reach and
      Enhancing Our Value.

PMID- 29653933
TI  - In Reply.

PMID- 29653930
TI  - Cardiac Rotational Mechanics As a Predictor of Myocardial Recovery in Heart
      Failure Patients Undergoing Chronic Mechanical Circulatory Support: A Pilot
      Study.
AB  - BACKGROUND: Impaired qualitative and quantitative left ventricular (LV)
      rotational mechanics predict cardiac remodeling progression and prognosis after
      myocardial infarction. We investigated whether cardiac rotational mechanics can
      predict cardiac recovery in chronic advanced cardiomyopathy patients. METHODS AND
      RESULTS: Sixty-three patients with advanced and chronic dilated cardiomyopathy
      undergoing implantation of LV assist device (LVAD) were prospectively
      investigated using speckle tracking echocardiography. Acute heart failure
      patients were prospectively excluded. We evaluated LV rotational mechanics
      (apical and basal LV twist, LV torsion) and deformational mechanics
      (circumferential and longitudinal strain) before LVAD implantation. Cardiac
      recovery post-LVAD implantation was defined as (1) final resulting LV ejection
      fraction >=40%, (2) relative LV ejection fraction increase >=50%, (iii) relative
      LV end-systolic volume decrease >=50% (all 3 required). Twelve patients fulfilled
      the criteria for cardiac recovery (Rec Group). The Rec Group had significantly
      less impaired pre-LVAD peak LV torsion compared with the Non-Rec Group. Notably,
      both groups had similarly reduced pre-LVAD LV ejection fraction. By receiver
      operating characteristic curve analysis, pre-LVAD peak LV torsion of 0.35
      degrees/cm had a 92% sensitivity and a 73% specificity in predicting cardiac
      recovery. Peak LV torsion before LVAD implantation was found to be an independent
      predictor of cardiac recovery after LVAD implantation (odds ratio, 0.65 per 0.1
      degrees/cm [0.49-0.87]; P=0.014). CONCLUSIONS: LV rotational mechanics seem to be
      useful in selecting patients prone to cardiac recovery after mechanical unloading
      induced by LVADs. Future studies should investigate the utility of these markers
      in predicting durable cardiac recovery after the explantation of the cardiac
      assist device.

PMID- 29653934
TI  - Fingerprint Drug Analysis: Overcoming Pitfalls and Heading Toward the Future?

PMID- 29653935
TI  - High-Sensitivity Cardiac Troponin T: Association of Creatine Kinase Catalytic
      Activity With the 99th Percentile.

PMID- 29653936
TI  - Atmospheric Pressure Chemical Ionization Is a Suboptimal Ionization Source for
      Steroids.

PMID- 29653937
TI  - Unusual case of suspected recurrent scarlet fever in a UK serviceman.
AB  - The UK prevalence of scarlet fever, a Group A streptococcal infection, is
      increasing. We present an unusual case of suspected recurrent scarlet fever in a
      member of the UK Armed Forces. Treatments, occupational implication and public
      health measures to mitigate the risk of disease spread.

PMID- 29653938
TI  - Lessons identified from the 2017 Manchester and London terrorism incidents. Part
      1: introduction and the prehospital phase.
AB  - This is the first article in a three-part series detailing the lessons identified
      during the NHS England clinical debrief meetings which followed the response to
      the 2017 Manchester and London terrorist incidents. It covers the prehospital
      phase including the overall key learning points, timeline information, scene
      challenges, resource utilisation, triage, distribution and helicopter emergency
      medical service feedback.

PMID- 29653939
TI  - Adherence to reporting guidelines and clinical trial registration policies in
      oncology journals: a cross-sectional review.
AB  - Reporting guidelines (RG) aim to improve research transparency and ensure high
      quality study reporting. Similarly, clinical trial registration policies aim to
      reduce bias in results reporting by ensuring prospective registration of all
      trial outcomes. Failure to adhere to quality standards documented in RGs may
      result in low-quality and irreproducible research. Herein, we investigate the
      adherence to common RGs and trial registration policies in 21 oncology journals.
      We surveyed the Instructions for Authors page for each of the included oncology
      journals for adherence to common reporting guidelines and trial registration
      policies. We corresponded with editors to determine accepted study types and
      cross-referenced this information with a journal's RGs and trial registration
      policies to calculate the per cent of journals that adhere to a specific
      guideline or policy. 76.2% (16/21) of oncology journals surveyed adhere to
      Consolidated Standards of Reporting Trials guidelines for clinical trials while
      only 33.3% (7/21) adhere to Strengthening the Reporting of Observational Studies
      in Epidemiology for observational studies. Similarly, 76.2% (16/21) of oncology
      journals adhere to clinical trial registration policies. We further demonstrate
      that journal adherence to RGs positively affects author reporting, despite
      adherence to trial registration policies showing no such benefit. Our results
      show that oncology journals adhere to RGs and trial registration policies at a
      higher rate than other specialties, but nonetheless show room for improvement. We
      conclude that oncology journal adherence to RGs and trial registration policies
      is encouraging, but nonetheless suboptimal. We recommend the adoption of RGs and
      trial registration policies by all oncology journals.

PMID- 29653940
TI  - The Atypical Rho GTPase CHW-1 Works with SAX-3/Robo To Mediate Axon Guidance in
      Caenorhabditis elegans.
AB  - During development, neuronal cells extend an axon toward their target destination
      in response to a cue to form a properly functioning nervous system. Rho proteins,
      Ras-related small GTPases that regulate cytoskeletal organization and dynamics,
      cell adhesion, and motility, are known to regulate axon guidance. Despite
      extensive knowledge about canonical Rho proteins (RhoA/Rac1/Cdc42), little is
      known about the Caenorhabditis elegans (C. elegans) atypical Cdc42-like family
      members CHW-1 and CRP-1 in regards to axon pathfinding and neuronal migration.
      chw-1(Chp/Wrch) encodes a protein that resembles human Chp (Wrch-2/RhoV) and Wrch
      1 (RhoU), and crp-1 encodes for a protein that resembles TC10 and TCL. Here, we
      show that chw-1 works redundantly with crp-1 and cdc-42 in axon guidance.
      Furthermore, proper levels of chw-1 expression and activity are required for
      proper axon guidance. When examining CHW-1 GTPase mutants, we found that the
      native CHW-1 protein is likely partially activated, and mutations at a conserved
      residue (position 12 using Ras numbering, position 18 in CHW-1) alter axon
      guidance and neural migration. Additionally, we showed that chw-1 genetically
      interacts with the guidance receptor sax-3 in PDE neurons. Finally, in VD/DD
      motor neurons, chw-1 works downstream of sax-3 to control axon guidance. In
      summary, this is the first study implicating the atypical Rho GTPases chw-1 and
      crp-1 in axon guidance. Furthermore, this is the first evidence of genetic
      interaction between chw-1 and the guidance receptor sax-3 These data suggest that
      chw-1 is likely acting downstream and/or in parallel to sax-3 in axon guidance.

PMID- 29653942
TI  - Resistance to Antibody-Drug Conjugates.
AB  - Antibody-drug conjugates (ADC) are multicomponent molecules constituted by an
      antibody covalently linked to a potent cytotoxic agent. ADCs combine high target
      specificity provided by the antibody together with strong antitumoral properties
      provided by the attached cytotoxic agent. At present, four ADCs have been
      approved and over 60 are being explored in clinical trials. Despite their
      effectiveness, resistance to these drugs unfortunately occurs. Efforts to
      understand the bases underlying such resistance are being carried out with the
      final purpose of counteracting them. In this review, we report described
      mechanisms of resistance to ADCs used in the clinic along with other potential
      ones that may contribute to resistance acquisition. We also discuss strategies to
      overcome resistance to ADCs. Cancer Res; 78(9); 2159-65. (c)2018 AACR.

PMID- 29653943
TI  - Sirtuin-1 (SIRT1) stimulates growth-plate chondrogenesis by attenuating the PERK
      eIF-2alpha-CHOP pathway in the unfolded protein response.
AB  - The NAD+-dependent deacetylase sirtuin-1 (SIRT1) has emerged as an important
      regulator of chondrogenesis and cartilage homeostasis, processes that are
      important for physiological skeletal growth and that are dysregulated in
      osteoarthritis. However, the functional role and underlying mechanism by which
      SIRT1 regulates chondrogenesis remain unclear. Using cultured rat metatarsal
      bones and chondrocytes isolated from rat metatarsal rudiments, here we studied
      the effects of the SIRT1 inhibitor EX527 or of SIRT1 siRNA on chondrocyte
      proliferation, hypertrophy, and apoptosis. We show that EX527 or SIRT1 siRNA
      inhibits chondrocyte proliferation and hypertrophy and induces apoptosis. We also
      observed that SIRT1 inhibition mainly induces the PERK-eIF-2alpha-CHOP axis of
      the endoplasmic reticulum (ER) stress response in growth-plate chondrocytes. Of
      note, EX527- or SIRT1 siRNA-mediated inhibition of metatarsal growth and growth
      plate chondrogenesis were partly neutralized by phenylbutyric acid, a chemical
      chaperone that attenuates ER stress. Moreover, EX527-mediated impairment of
      chondrocyte function (i.e. of chondrocyte proliferation, hypertrophy, and
      apoptosis) was partly reversed in CHOP-/- cells. We also present evidence that
      SIRT1 physically interacts with and deacetylates PERK. Collectively, our findings
      indicate that SIRT1 deacetylates PERK and attenuates the PERK-eIF-2alpha-CHOP
      axis of the unfolded protein response pathway and thereby promotes growth-plate
      chondrogenesis and longitudinal bone growth.

PMID- 29653944
TI  - Selective inhibition of intestinal guanosine 3',5'-cyclic monophosphate signaling
      by small-molecule protein kinase inhibitors.
AB  - The guanosine 3',5'-cyclic monophosphate (cGMP)-dependent protein kinase II
      (cGKII) serine/threonine kinase relays signaling through guanylyl cyclase C (GCC)
      to control intestinal fluid homeostasis. Here, we report the discovery of small
      molecule inhibitors of cGKII. These inhibitors were imidazole-aminopyrimidines,
      which blocked recombinant human cGKII at submicromolar concentrations but
      exhibited comparatively little activity toward the phylogenetically related
      protein kinases cGKI and cAMP-dependent protein kinase (PKA). Whereas
      aminopyrimidyl motifs are common in protein kinase inhibitors, molecular modeling
      of these imidazole-aminopyrimidines in the ATP-binding pocket of cGKII indicated
      an unconventional binding mode that directs their amine substituent into a narrow
      pocket delineated by hydrophobic residues of the hinge and the alphaC-helix.
      Crucially, this set of residues included the Leu-530 gatekeeper, which is not
      conserved in cGKI and PKA. In intestinal organoids, these compounds blocked cGKII
      dependent phosphorylation of the vasodilator-stimulated phosphoprotein (VASP). In
      mouse small intestinal tissue, cGKII inhibition significantly attenuated the
      anion secretory response provoked by the GCC-activating bacterial heat-stable
      toxin (STa), a frequent cause of infectious secretory diarrhea. In contrast, both
      PKA-dependent VASP phosphorylation and intestinal anion secretion were unaffected
      by treatment with these compounds, whereas experiments with T84 cells indicated
      that they weakly inhibit the activity of cAMP-hydrolyzing phosphodiesterases. As
      these protein kinase inhibitors are the first to display selective inhibition of
      cGKII, they may expedite research on cGMP signaling and may aid future
      development of therapeutics for managing diarrheal disease and other pathogenic
      syndromes that involve cGKII.

PMID- 29653941
TI  - Guidelines for the investigation of chronic diarrhoea in adults: British Society
      of Gastroenterology, 3rd edition.
AB  - Chronic diarrhoea is a common problem, hence clear guidance on investigations is
      required. This is an updated guideline from 2003 for the investigations of
      chronic diarrhoea commissioned by the Clinical Services and Standards Committee
      of the British Society of Gastroenterology (BSG). This document has undergone
      significant revision in content through input by 13 members of the Guideline
      Development Group (GDG) representing various institutions. The GRADE system was
      used to appraise the quality of evidence and grading of recommendations.

PMID- 29653945
TI  - Cullin-3-RING ubiquitin ligase activity is required for striated muscle function
      in mice.
AB  - Control of protein homeostasis is an essential cellular process that, when
      perturbed, can result in the deregulation or toxic accumulation of proteins.
      Owing to constant mechanical stress, striated muscle proteins are particularly
      prone to wear and tear and require several protein quality-control mechanisms to
      coordinate protein turnover and removal of damaged proteins. Kelch-like proteins,
      substrate adapters for the Cullin-3 (Cul3)-RING ligase (CRL3) complex, are
      emerging as critical regulators of striated muscle development and function,
      highlighting the importance of Cul3-mediated proteostasis in muscle function. To
      explore the role of Cul3-mediated proteostasis in striated muscle, here we
      deleted Cul3 specifically in either skeletal muscle (SkM-Cul3 KO) or
      cardiomyocytes (CM-Cul3 KO) of mice. The loss of Cul3 caused neonatal lethality
      and dramatic alterations in the proteome, which were unique to each striated
      muscle type. Many of the proteins whose expression was significantly changed in
      the SkM-Cul3 KO were components of the extracellular matrix and sarcomere,
      whereas proteins altered in the CM-Cul3 KO were involved in metabolism. These
      findings highlight the requirement for striated muscle-specific CRL3 activity and
      indicate how the CRL3 complex can control different nodes of protein interaction
      networks in different types of striated muscle. Further identification of Cul3
      substrates, and how these substrates are targeted, may reveal therapeutic targets
      and treatment regimens for striated muscle diseases.

PMID- 29653947
TI  - "Recent lessons learned in the management of acute exacerbation of idiopathic
      pulmonary fibrosis." Yasuhiro Kondoh, Vincent Cottin and Kevin K. Brown. Eur
      Respir Rev 2017; 26: 170050.

PMID- 29653946
TI  - A European regulatory perspective on cystic fibrosis: current treatments, trends
      in drug development and translational challenges for CFTR modulators.
AB  - In this article we analyse the current authorised treatments and trends in early
      drug development for cystic fibrosis (CF) in the European Union for the time
      period 2000-2016. The analysis indicates a significant improvement in the
      innovation and development of new potential medicines for CF, shifting from
      products that act on the symptoms of the disease towards new therapies targeting
      the cause of CF. However, within these new innovative medicines, results for CF
      transmembrane conductance regulator (CFTR) modulators indicate that one major
      challenge for turning a CF concept product into an actual medicine for the
      benefit of patients resides in the fact that, although pre-clinical models have
      shown good predictability for certain mutations, a good correlation to clinical
      end-points or biomarkers (e.g. forced expiratory volume in 1 s and sweat
      chloride) for all mutations has not yet been achieved. In this respect, the use
      of alternative end-points and innovative nonclinical models could be helpful for
      the understanding of those translational discrepancies. Collaborative endeavours
      to promote further research and development in these areas as well as early
      dialogue with the regulatory bodies available at the European competent
      authorities are recommended.

PMID- 29653948
TI  - Precision medicine and personalising therapy in pulmonary hypertension: seeing
      the light from the dawn of a new era.
AB  - Pulmonary hypertension (PH) and pulmonary arterial hypertension (PAH) include
      different cardiopulmonary disorders in which the interaction of multiple genes
      with environmental and behavioural factors modulates the onset and the
      progression of these severe conditions. Although the development of therapeutic
      agents that modulate abnormalities in three major pathobiological pathways for
      PAH has revolutionised our approach to the treatment of PAH, the long-term
      survival rate remains unsatisfactory. Accumulating evidence has underlined that
      clinical outcomes and responses to therapy in PAH are modified by multiple
      factors, including genetic variations, which will be different for each
      individual. Since precision medicine, also known as stratified medicine or
      personalised medicine, aims to better target intervention to the individual while
      maximising benefit and minimising harm, it has significant potential advantages.
      This article aims to assemble and discuss the different initiatives that are
      currently underway in the PH/PAH fields together with the opportunities and
      prospects for their use in the near future.

PMID- 29653949
TI  - How should we monitor patients with acute respiratory failure treated with
      noninvasive ventilation?
AB  - Noninvasive ventilation (NIV) is currently one of the most commonly used support
      methods in hypoxaemic and hypercapnic acute respiratory failure (ARF). With
      advancing technology and increasing experience, not only are indications for NIV
      getting broader, but more severe patients are treated with NIV. Depending on
      disease type and clinical status, NIV can be applied both in the general ward and
      in high-dependency/intensive care unit settings with different environmental
      opportunities. However, it is important to remember that patients with ARF are
      always very fragile with possible high mortality risk. The delay in recognition
      of unresponsiveness to NIV, progression of respiratory failure or new-onset
      complications may result in devastating and fatal outcomes. Therefore, it is
      crucial to understand that timely action taken according to monitoring variables
      is one of the key elements for NIV success. The purpose of this review is to
      outline basic and advanced monitoring techniques for NIV during an ARF episode.

PMID- 29653950
TI  - Personalised medicine in interstitial lung diseases: Number 6 in the Series
      "Personalised medicine in respiratory diseases" Edited by Renaud Louis and
      Nicolas Roche.
AB  - Interstitial lung diseases in general, and idiopathic pulmonary fibrosis in
      particular, are complex disorders with multiple pathogenetic pathways, various
      disease behaviour profiles and different responses to treatment, all facets that
      make personalised medicine a highly attractive concept. Personalised medicine is
      aimed at describing distinct disease subsets taking into account individual
      lifestyle, environmental exposures, genetic profiles and molecular pathways. The
      cornerstone of personalised medicine is the identification of biomarkers that can
      be used to inform diagnosis, prognosis and treatment stratification. At present,
      no data exist validating a personalised approach in individual diseases. However,
      the importance of the goal amply justifies the characterisation of genotype and
      pathway signatures with a view to refining prognostic evaluation and trial
      design, with the ultimate aim of selecting treatments according to profiles in
      individual patients.

PMID- 29653951
TI  - SLAM-seq Identifies Direct Transcriptional Targets of BRD4 and MYC.
AB  - BRD4 activates RNA Pol2-dependent transcription, whereas MYC activates a confined
      set of target genes.

PMID- 29653952
TI  - Larotrectinib Has Antitumor Activity in TRK+ Pediatric Solid Tumors.
AB  - Larotrectinib achieved a 93% response rate in pediatric patients with TRK fusion
      positive tumors.

PMID- 29653953
TI  - The IL15 Superagonist ALT-803 plus Nivolumab Has Antitumor Activity.
AB  - Nivolumab in combination with ALT-803 is tolerable and achieves responses in
      patients with NSCLC.

PMID- 29653954
TI  - Glioblastoma Stem Cell-Tumor Cell Cross-talk Drives Gliomagenesis.
AB  - Reciprocal paracrine signaling between GBM stem cells and GBM cells promotes
      tumor growth.

PMID- 29653956
TI  - Burden of Proof for Tolvaptan in ADPKD: Did REPRISE Provide the Answer?

PMID- 29653957
TI  - Management of the Incidental Kidney Mass in the Nephrology Clinic.

PMID- 29653958
TI  - Treatment of Depression in CKD Patients with an SSRI: Why Things Don't Always
      Turn Out as You Expect.

PMID- 29653955
TI  - Mechanisms of Oncogene-Induced Replication Stress: Jigsaw Falling into Place.
AB  - Oncogene activation disturbs cellular processes and accommodates a complex
      landscape of changes in the genome that contribute to genomic instability, which
      accelerates mutation rates and promotes tumorigenesis. Part of this cellular
      turmoil involves deregulation of physiologic DNA replication, widely described as
      replication stress. Oncogene-induced replication stress is an early driver of
      genomic instability and is attributed to a plethora of factors, most notably
      aberrant origin firing, replication-transcription collisions, reactive oxygen
      species, and defective nucleotide metabolism.Significance: Replication stress is
      a fundamental step and an early driver of tumorigenesis and has been associated
      with many activated oncogenes. Deciphering the mechanisms that contribute to the
      replication stress response may provide new avenues for targeted cancer
      treatment. In this review, we discuss the latest findings on the DNA replication
      stress response and examine the various mechanisms through which activated
      oncogenes induce replication stress. Cancer Discov; 8(5); 537-55. (c)2018 AACR.

PMID- 29653960
TI  - Hepatobiliary Disposition of Atovaquone: A Case of Mechanistically Unusual
      Biliary Clearance.
AB  - Atovaquone, an antiprotozoal and antipneumocystic agent, is predominantly cleared
      by biliary excretion of unchanged parent drug. Atovaquone is >=10,000-fold
      concentrated in human bile relative to unbound plasma. Even after correcting for
      apparent nonspecific binding and incomplete solubility in bile, atovaquone is
      still concentrated >=100-fold in bile, consistent with active biliary excretion.
      Mechanisms of atovaquone hepatobiliary disposition were studied using a
      multiexperimental in vitro and in vivo approach. Atovaquone uptake was not
      elevated in HEK293 cells singly overexpressing OATP1B1, OATP1B3, OATP2B1, OCT1,
      NTCP, or OAT2. Hepatocyte uptake of atovaquone was not impaired by OATP and OCT
      inhibitor cocktail (rifamycin and imipramine). Atovaquone liver-to-blood ratio at
      distributional equilibrium was not reduced in Oatp1a/1b and Oct1/2 knockout mice.
      Atovaquone exhibited efflux ratios of approximately unity in P-gp and BCRP
      overexpressing MDCK cell monolayers and did not display enhanced uptake in MRP2
      vesicles. Biliary and canalicular clearance were not decreased in P-gp, Bcrp,
      Mrp2, and Bsep knockout rats. In the present study, we rule out the involvement
      of major known basolateral uptake and bile canalicular efflux transporters in the
      hepatic uptake and biliary excretion of atovaquone. This is the first known
      example of a drug cleared by biliary excretion in humans, with extensive biliary
      concentration, which is not transported by the mechanisms investigated herein.

PMID- 29653959
TI  - Remote Atmospheric Pressure Infrared Matrix-Assisted Laser Desorption-Ionization
      Mass Spectrometry (Remote IR-MALDI MS) of Proteins.
AB  - Remote Infrared Matrix-Assisted Laser Desorption/Ionization (Remote IR-MALDI)
      system using tissue endogenous water as matrix was shown to enable in vivo real
      time mass spectrometry analysis with minimal invasiveness. Initially the system
      was used to detect metabolites and lipids. Here, we demonstrate its capability to
      detect and analyze peptides and proteins. Very interestingly, the corresponding
      mass spectra show ESI-like charge state distribution, opening many applications
      for structural elucidation to be performed in real-time by Top-Down strategy. The
      charge states show no dependence toward laser wavelength or length of the
      transfer tube. Indeed, remote analysis can be performed 5 m away from the mass
      spectrometer without modification of spectra. On the contrary, addition of
      glycerol to water shift the charge state distributions toward even higher charge
      states. The desorption/ionization process is very soft, allowing to maintain
      protein conformation as in ESI. Observation of proteins and similar spectral
      features on tissue, when protein standards are deposited on raw tissue pieces,
      could potentially open the way to their direct analysis from biological samples.
      This also brings interesting features that could contribute to the understanding
      of IR MALDI ionization mechanism.

PMID- 29653961
TI  - Analysis of the Indacaterol-Regulated Transcriptome in Human Airway Epithelial
      Cells Implicates Gene Expression Changes in the Adverse and Therapeutic Effects
      of beta2-Adrenoceptor Agonists.
AB  - The contribution of gene expression changes to the adverse and therapeutic
      effects of beta2-adrenoceptor agonists in asthma was investigated using human
      airway epithelial cells as a therapeutically relevant target. Operational model
      fitting established that the long-acting beta2-adrenoceptor agonists (LABA)
      indacaterol, salmeterol, formoterol, and picumeterol were full agonists on BEAS
      2B cells transfected with a cAMP-response element reporter but differed in
      efficacy (indacaterol >= formoterol > salmeterol >= picumeterol). The
      transcriptomic signature of indacaterol in BEAS-2B cells identified 180, 368,
      252, and 10 genes that were differentially expressed (>1.5- to <0.67-fold) after
      1-, 2-, 6-, and 18-hour of exposure, respectively. Many upregulated genes (e.g.,
      AREG, BDNF, CCL20, CXCL2, EDN1, IL6, IL15, IL20) encode proteins with
      proinflammatory activity and are annotated by several, enriched gene ontology
      (GO) terms, including cellular response to interleukin-1, cytokine activity, and
      positive regulation of neutrophil chemotaxis The general enriched GO term
      extracellular space was also associated with indacaterol-induced genes, and many
      of those, including CRISPLD2, DMBT1, GAS1, and SOCS3, have putative anti
      inflammatory, antibacterial, and/or antiviral activity. Numerous indacaterol
      regulated genes were also induced or repressed in BEAS-2B cells and human primary
      bronchial epithelial cells by the low efficacy LABA salmeterol, indicating that
      this genomic effect was neither unique to indacaterol nor restricted to the BEAS
      2B airway epithelial cell line. Collectively, these data suggest that the
      consequences of inhaling a beta2-adrenoceptor agonist may be complex and involve
      widespread changes in gene expression. We propose that this genomic effect
      represents a generally unappreciated mechanism that may contribute to the adverse
      and therapeutic actions of beta2-adrenoceptor agonists in asthma.

PMID- 29653962
TI  - FF-10502, an Antimetabolite with Novel Activity on Dormant Cells, Is Superior to
      Gemcitabine for Targeting Pancreatic Cancer Cells.
AB  - In this paper, we report that 1-(2-deoxy-2-fluoro-4-thio-beta-d-arabinofuranosyl)
      cytosine (FF-10502), a pyrimidine nucleoside antimetabolite with a chemical
      structure similar to gemcitabine, shows beneficial anticancer activity via a
      novel mechanism of action on dormant cells. The growth inhibition of pancreatic
      cancer cell lines by FF-10502 (IC50, 60-330 nM) was moderately weaker than that
      by gemcitabine in vitro. In contrast, an in vivo orthotopic implantation model in
      mice with established human pancreatic cancer cell line, SUIT-2, revealed no
      mortality with FF-10502 intravenous treatment, which was related to regression of
      implanted tumor and little metastasis, whereas 75% of the mice treated with
      gemcitabine died by day 128. Two in vivo patient-derived xenograft models with
      gemcitabine-resistant pancreatic cancer cells also demonstrated complete tumor
      growth suppression with FF-10502, but only partial inhibition with gemcitabine.
      We also investigated the mechanism of action of FF-10502 by using dormant cancer
      cells, which are reportedly involved in the development of resistance to
      chemotherapy. In vitro serum starvation-induced dormant SUIT-2 cells developed
      resistance to gemcitabine even in combination with DNA damage inducers (DDIs;
      H2O2, cisplatin, and temozolomide). Interestingly, FF-10502 in combination with
      DDIs significantly induced concentration-dependent cell death in accordance with
      enhanced DNA damage. FF-10502 was far more potent than gemcitabine in inhibiting
      DNA polymerase beta, which may explain the difference in dormant cell injury,
      although further investigations for direct evidences are necessary. In
      conclusion, our study demonstrated the beneficial antitumor effects of FF-10502
      in clinically relevant in vivo models, and suggests the importance of preventing
      DNA repair unlike gemcitabine.

PMID- 29653963
TI  - NOX4 Deletion in Male Mice Exacerbates the Effect of Ethanol on Trabecular Bone
      and Osteoblastogenesis.
AB  - Chronic alcohol consumption increases bone resorption and decreases bone
      formation. A major component of ethanol (EtOH) pathology in bone is the
      generation of excess reactive oxygen species (ROS). The ROS-generating NADPH
      oxidase-4 (NOX4) is proposed to drive much of the EtOH-induced suppression of
      bone formation. Here, 13-week-old male wild-type (WT) and NOX4-/- mice were pair
      fed (PF) a high-fat (35%), Lieber-DeCarli liquid diet with or without EtOH at 30%
      of their total calories for 12 weeks. Micro-computed tomography analysis
      demonstrated significant decreases in trabecular bone volume/total volume (BV/TV)
      percentage and cortical thickness in WT, EtOH-fed mice compared with PF controls.
      EtOH-fed NOX4-/- mice also displayed decreased trabecular BV/TV and trabecular
      number compared with PF (P < 0.05). However, NOX4-/- mice were protected against
      EtOH-induced decreases in cortical thickness (P < 0.05) and decreases in
      collagen1 and osteocalcin mRNA expression in cortical bone (P < 0.05). In WT and
      NOX4-/- vertebral bone, EtOH suppressed expression of Wnt signaling components
      that promote osteoblast maturation. A role for NOX4 in EtOH inhibition of
      osteoblast differentiation was further demonstrated by protection against EtOH
      inhibition of osteoblastogenesis in ex vivo bone marrow cultures from NOX4-/-,
      but not p47phox-/- mice lacking active NADPH oxidase-2. However, bone marrow
      cultures from NOX4-/- mice formed fewer osteoblastic colonies compared with WT
      cultures (P < 0.05), suggesting a role for NOX4 in the maintenance of mesenchymal
      progenitor cell populations. These data suggest that NOX4 deletion is partially
      protective against EtOH effects on osteoblast differentiation, but may predispose
      bone to osteogenic impairments.

PMID- 29653964
TI  - TRRAP is essential for regulating the accumulation of mutant and wild-type p53 in
      lymphoma.
AB  - Tumors accumulate high levels of mutant p53 (mutp53), which contributes to mutp53
      gain-of-function properties. The mechanisms that underlie such excessive
      accumulation are not fully understood. To discover regulators of mutp53 protein
      accumulation, we performed a large-scale RNA interference screen in a Burkitt
      lymphoma cell line model. We identified transformation/transcription domain
      associated protein (TRRAP), a constituent of several histone acetyltransferase
      complexes, as a critical positive regulator of both mutp53 and wild-type p53
      levels. TRRAP silencing attenuated p53 accumulation in lymphoma and colon cancer
      models, whereas TRRAP overexpression increased mutp53 levels, suggesting a role
      for TRRAP across cancer entities and p53 mutations. Through clustered regularly
      interspaced short palindromic repeats (CRISPR)-Cas9 screening, we identified a
      109-amino-acid region in the N-terminal HEAT repeat region of TRRAP that was
      crucial for mutp53 stabilization and cell proliferation. Mass spectrometric
      analysis of the mutp53 interactome indicated that TRRAP silencing caused
      degradation of mutp53 via the MDM2-proteasome axis. This suggests that TRRAP is
      vital for maintaining mutp53 levels by shielding it against the natural p53
      degradation machinery. To identify drugs that alleviated p53 accumulation
      similarly to TRRAP silencing, we performed a small-molecule drug screen and found
      that inhibition of histone deacetylases (HDACs), specifically HDAC1/2/3,
      decreased p53 levels to a comparable extent. In summary, here we identify TRRAP
      as a key regulator of p53 levels and link acetylation-modifying complexes to p53
      protein stability. Our findings may provide clues for therapeutic targeting of
      mutp53 in lymphoma and other cancers.

PMID- 29653965
TI  - Patients with CD3G mutations reveal a role for human CD3gamma in Treg diversity
      and suppressive function.
AB  - Integrity of the T-cell receptor/CD3 complex is crucial for positive and negative
      selection of T cells in the thymus and for effector and regulatory functions of
      peripheral T lymphocytes. In humans, CD3D, CD3E, and CD3Z gene defects are a
      cause of severe immune deficiency and present early in life with increased
      susceptibility to infections. By contrast, CD3G mutations lead to milder
      phenotypes, mainly characterized by autoimmunity. However, the role of CD3gamma
      in establishing and maintaining immune tolerance has not been elucidated. In this
      manuscript, we aimed to investigate abnormalities of T-cell repertoire and
      function in patients with genetic defects in CD3G associated with autoimmunity.
      High throughput sequencing was used to study composition and diversity of the T
      cell receptor beta (TRB) repertoire in regulatory T cells (Tregs), conventional
      CD4+ (Tconv), and CD8+ T cells from 6 patients with CD3G mutations and healthy
      controls. Treg function was assessed by studying its ability to suppress
      proliferation of Tconv cells. Treg cells of patients with CD3G defects had
      reduced diversity, increased clonality, and reduced suppressive function. The TRB
      repertoire of Tconv cells from patients with CD3G deficiency was enriched for
      hydrophobic amino acids at positions 6 and 7 of the CDR3, a biomarker of self
      reactivity. These data demonstrate that the T-cell repertoire of patients with
      CD3G mutations is characterized by a molecular signature that may contribute to
      the increased rate of autoimmunity associated with this condition.

PMID- 29653966
TI  - The impact of a changing atmosphere on chloroplast function, photosynthesis,
      yield, and food security.
AB  - A convergence of global factors is adding to the difficulties of securing a
      sustainable supply of food and feed to support the increasing global population.
      The positive impact of the rise in atmospheric CO2 on photosynthesis is more than
      offset by the increase in average global temperatures accompanying the change in
      atmospheric composition. This article provides a brief overview of how these
      adverse events affect some of the critical molecular processes of the chloroplast
      and by extension how this impacts the yields of the major crops. Although the
      tools are available to introduce genetic elements in most crops that will
      mitigate these adverse factors, the time needed to validate and optimize these
      traits can be extensive. There is a major concern that at the current rate of
      change to atmospheric composition and the accompanying rise in temperature the
      benefits of these traits may be rendered less effective soon after their
      introduction.

PMID- 29653967
TI  - Increasing metabolic potential: C-fixation.
AB  - Due to the growing world population, crop yields must increase to meet the rising
      demand. Crop plants also require adaptation to optimize performance in the
      changing environments caused by climate change. Improving photosynthetic carbon
      fixation is a promising, albeit technically challenging, strategy whose potential
      has only just begun to be considered in breeding programmes. Ribulose-1,5
      bisphosphate carboxylase/oxygenase (Rubisco), a fundamental enzyme of carbon
      fixation, is extremely inefficient and many strategies to improve photosynthesis
      focus on overcoming the limitations of this enzyme, either by improving Rubisco
      activity and regulation or by improving the supply of substrates. Although
      progress is being made, the need to tailor solutions for each crop and their
      respective environments has been highlighted. Even so, continuing research will
      be required to achieve these objectives and to grow crops more sustainably in the
      future.

PMID- 29653968
TI  - Developmental Timing Is Everything: TZP and Phytochrome Signaling.

PMID- 29653969
TI  - So Inclined: Phosphate Status and Leaf Angle in Rice.

PMID- 29653970
TI  - Mesenchymal stromal cells: a novel therapy for the treatment of chronic
      obstructive pulmonary disease?
AB  - COPD is characterised by tissue destruction and inflammation. Given the lack of
      curative treatments and the progressive nature of the disease, new treatments for
      COPD are highly relevant. In vitro cell culture and animal studies have
      demonstrated that mesenchymal stromal cells (MSCs) have the capacity to modify
      immune responses and to enhance tissue repair. These properties of MSCs provided
      a rationale to investigate their potential for treatment of a variety of
      diseases, including COPD. Preclinical models support the hypothesis that MSCs may
      have clinical efficacy in COPD. However, although clinical trials have
      demonstrated the safety of MSC treatment, thus far they have not provided
      evidence for MSC efficacy in the treatment of COPD. In this review, we discuss
      the rationale for MSC-based cell therapy in COPD, the main findings from in vitro
      and in vivo preclinical COPD model studies, clinical trials in patients with COPD
      and directions for further research.

PMID- 29653971
TI  - Safety, Pharmacokinetics, and Dosimetry of a Long-Acting Radiolabeled
      Somatostatin Analog 177Lu-DOTA-EB-TATE in Patients with Advanced Metastatic
      Neuroendocrine Tumors.
AB  - Radiolabeled somatostatin analog therapy has become an established treatment
      method for patients with well to moderately differentiated unresectable or
      metastatic neuroendocrine tumors (NETs). The most frequently used somatostatin
      analogs in clinical practice are octreotide and octreotate. However, both
      peptides showed suboptimal retention within tumors. The aim of this first-in
      humans study is to explore the safety and dosimetry of a long-acting radiolabeled
      somatostatin analog, 177Lu-1, 4, 7, 10-tetra-azacyclododecane-1, 4, 7, 10
      tetraacetic acid-Evans blue-octreotate (177Lu-DOTA-EB-TATE). Methods: Eight
      patients (6 men and 2 women; age range, 27-61 y) with advanced metastatic NETs
      were recruited. Five patients received a single dose, 0.35-0.70 GBq (9.5-18.9
      mCi), of 177Lu-DOTA-EB-TATE and underwent serial whole-body planar and SPECT/CT
      scans at 2, 24, 72, 120, and 168 h after injection. The other 3 patients received
      intravenous injection of 0.28-0.41 GBq (7.5-11.1 mCi) of 177Lu-DOTATATE for the
      same imaging acquisition procedures at 1, 3, 4, 24, and 72 h after injection. The
      dosimetry was calculated using the OLINDA/EXM 1.1 software. Results:
      Administration of 177Lu-DOTA-EB-TATE was well tolerated, with no adverse symptoms
      being noticed or reported in any of the patients. Compared with 177Lu-DOTATATE,
      177Lu-DOTA-EB-TATE showed extended circulation in the blood and achieved a 7.9
      fold increase of tumor dose delivery. The total-body effective doses were 0.205
      +/- 0.161 mSv/MBq for 177Lu-DOTA-EB-TATE and 0.174 +/- 0.072 mSv/MBq for 177Lu
      DOTATATE. Significant dose delivery increases to the kidneys and bone marrow were
      also observed in patients receiving 177Lu-DOTA-EB-TATE compared with those
      receiving 177Lu-DOTATATE (3.2 and 18.2-fold, respectively). Conclusion: By
      introducing an albumin-binding moiety, 177Lu-DOTA-EB-TATE showed remarkably
      higher uptake and retention in NETs as well as significantly increased
      accumulation in the kidneys and red marrow. It has great potential to be used in
      peptide receptor radionuclide therapy for NETs with lower dose and less frequency
      of administration.

PMID- 29653972
TI  - 18F-FDG PET/CT in Autosomal Dominant Polycystic Kidney Disease Patients with
      Suspected Cyst Infection.
AB  - The objective of this study was to determine the value of 18F-FDG PET/CT for
      diagnosing renal or hepatic cyst infection in patients with autosomal dominant
      polycystic kidney disease (ADPKD). Methods: This retrospective, single-center
      study included all patients who had ADPKD and underwent 18F-FDG PET/CT because of
      suspected cyst infection between 2010 and 2017. Results: Thirty 18F-FDG PET/CT
      scans of 30 individual patients were included; 19 of them had positive results
      for cyst infection. According to a previously established clinical and
      biochemical reference standard, 18F-FDG PET/CT achieved a sensitivity of 88.9%, a
      specificity of 75.0%, a positive predictive value of 84.2%, and a negative
      predictive value of 81.8% for the diagnosis of cyst infection. In 5 cases, 18F
      FDG PET/CT suggested that the symptoms could be explained by a different
      pathologic process, including pneumonia (n = 1), generalized peritonitis (n = 1),
      pancreatitis (n = 1), colitis (n = 1), and cholangitis (n = 1). The total
      duration of the hospital stay and the duration between the 18F-FDG PET/CT scan
      and hospital discharge for patients with 18F-FDG PET/CT scan results that were
      positive for cyst infection were significantly longer than those for patients
      with negative scan results (P = 0.005 and P = 0.009, respectively). Creatinine
      levels were significantly higher in patients with 18F-FDG PET/CT scan results
      that were positive for cyst infection than in patients with negative scan results
      (P = 0.015). Other comparisons of clinical parameters (age, sex, presence of
      fever [>38.5 degrees C] for more than 3 d, abdominal pain, history of solid-organ
      transplantation and nephrectomy, and immune status), laboratory values (C
      reactive protein level, leukocyte count, and estimated glomerular filtration
      rate), and microbiologic test results (blood and urine cultures) were not
      significantly different (P = 0.13-1.00) in patients with positive and negative
      18F-FDG PET/CT scan results. Conclusion: 18F-FDG PET/CT is a useful imaging
      modality for the evaluation of patients with ADPKD and suspected cyst infection.

PMID- 29653973
TI  - Radioiodinated Small-Molecule Tyrosine Kinase Inhibitor for HER2-Selective SPECT
      Imaging.
AB  - One of the most clinically relevant molecular aberrations in breast cancer is
      overexpression of human epidermal growth factor receptor type 2 (HER2). We aimed
      to develop a radiolabeled tyrosine kinase inhibitor for HER2-targeted breast
      cancer imaging. In this study, a radioiodinated analog (125/131I-IBA-CP) of the
      HER2-selective inhibitor CP724,714 was prepared and evaluated in HER2-positive or
      -negative subcutaneous human breast cancer xenografts. Methods: The CP724,714
      analog IBA-CP was synthesized and assayed for its inhibitory activities against
      HER2 and 6 other tyrosine kinases. 125/131I-IBA-CP was prepared using a copper
      mediated radioiodination method with enhanced labeling yield and molar activity.
      In vitro biologic activity, including specific and nonspecific binding of 131I
      IBA-CP to its HER2 kinase target, was assessed in different cell lines. In vivo
      small-animal 125I-IBA-CP SPECT imaging and biodistribution studies were conducted
      on mice bearing HER2-positive, HER2-negative, or epidermal growth factor receptor
      (EGFR)-positive tumors. Nonradioactive IBA-CP and the EGFR inhibitor erlotinib
      were used as blocking agents to investigate the binding specificity and
      selectivity of 125/131I-IBA-CP toward HER2 in vitro and in vivo. Additionally,
      125/131I-ICP was prepared by direct radioiodination of CP724,714 for comparison
      with 125/131I-IBA-CP. Results: IBA-CP displayed superior in vitro inhibitory
      activity (half-maximal inhibitory concentration, 16 nM) and selectivity for HER2
      over 6 other cancer-related tyrosine kinases. 125/131I-IBA-CP was prepared in a
      typical radiochemical yield of about 65% (decay-corrected), radiochemical purity
      of more than 98%, and molar activity of 42 GBq/MUmol at the end of synthesis.
      SPECT imaging revealed significantly higher uptake of 125I-IBA-CP than of 125I
      ICP in the HER2-positive MDA-MB-453 tumors. Uptake in the HER2-negative MCF-7
      tumors was much lower. Binding of 125I-IBA-CP in the MDA-MB-453 tumors was
      blocked by coinjection with an excess amount of IBA-CP, but not by erlotinib.
      Conclusion: The radiolabeled HER2-selective inhibitor 125/131I-IBA-CP is a
      promising probe for in vivo detection of HER2-positive tumors.

PMID- 29653974
TI  - Development of a Dedicated Rebinner with Rigid Motion Correction for the mMR
      PET/MR Scanner, and Validation in a Large Cohort of 11C-PIB Scans.
AB  - Head motion occurring during brain PET studies leads to image blurring and to
      bias in measured local quantities. The objective of this work was to implement a
      correction method for PET data acquired with the mMR synchronous PET/MR scanner.
      Methods: A list-mode-based motion-correction approach has been designed. The
      developed rebinner chronologically reads the recorded events from the Siemens
      list-mode file, applies the estimated geometric transformations, and frames the
      detected counts into sinograms. The rigid-body motion parameters were estimated
      from an initial dynamic reconstruction of the PET data. We then optimized the
      correction for 11C-Pittsburgh compound B (11C-PIB) scans using simulated and
      actual data with well-controlled motion. Results: An efficient list-mode-based
      motion correction approach has been implemented, fully optimized, and validated
      using simulated and actual PET data. The average spatial resolution loss induced
      by inaccuracies in motion parameter estimates and by the rebinning process was
      estimated to correspond to a 1-mm increase in full width at half maximum with
      motion parameters estimated directly from the PET data with a temporal frequency
      of 20 s. The results show that the rebinner can be safely applied to the 11C-PIB
      scans, allowing almost complete removal of motion-induced artifacts. The
      application of the correction method to a large cohort of 11C-PIB scans led to
      the following observations: first, that more than 21% of the scans were affected
      by motion greater than 10 mm (39% for subjects with Mini-Mental State Examination
      scores below 20), and second, that the correction led to quantitative changes in
      Alzheimer-specific cortical regions of up to 30%. Conclusion: The rebinner allows
      accurate motion correction at a cost of minimal resolution reduction. Application
      of the correction to a large cohort of 11C-PIB scans confirmed the necessity of
      systematically correcting for motion to obtain quantitative results.

PMID- 29653975
TI  - Predictive Factors of Response and Overall Survival in Patients with Castration
      Resistant Metastatic Prostate Cancer Undergoing 177Lu-PSMA Therapy.

PMID- 29653976
TI  - Reply: 6"-18F-Fluoromaltotriose PET Evaluation in Escherichia Coli-Induced
      Myositis: Is There Uptake Saturation in Control?

PMID- 29653977
TI  - Radioactive Iodine Therapy for Differentiated Thyroid Cancer: Lessons from
      Confronting Controversial Literature on Risks for Secondary Malignancy.

PMID- 29653978
TI  - Potential Impact of 68Ga-PSMA-11 PET/CT on the Planning of Definitive Radiation
      Therapy for Prostate Cancer.
AB  - Standard-of-care imaging for initial staging of prostate cancer (PCa)
      underestimates disease burden. Prostate-specific membrane antigen (PSMA) PET/CT
      detects PCa metastasis with superior accuracy, having a potential impact on the
      planning of definitive radiation therapy (RT) for nonmetastatic PCa. Our
      objectives were to determine how often definitive RT planning based on standard
      target volumes covers 68Ga-PSMA-11 PET/CT-defined disease and to assess the
      potential impact of 68Ga-PSMA-11 PET/CT on definitive RT planning. Methods: This
      was a post hoc analysis of an intention-to-treat population of 73 patients with
      localized PCa without prior local therapy who underwent 68Ga-PSMA PET/CT for
      initial staging as part of an investigational new drug trial. Eleven of the 73
      were intermediate-risk (15%), 33 were high-risk (45%), 22 were very-high-risk
      (30%), and 7 were N1 (9.5%). Clinical target volumes (CTVs), which included the
      prostate, seminal vesicles, and (in accord with the Radiation Therapy Oncology
      Group consensus guidelines) pelvic lymph nodes (LNs), were contoured on the CT
      portion of the PET/CT images by a radiation oncologist masked to the PET
      findings. 68Ga-PSMA-11 PET/CT images were analyzed by a nuclear medicine
      physician. 68Ga-PSMA-11-positive lesions not covered by planning volumes based on
      the CTVs were considered to have a major potential impact on treatment planning.
      Results: All patients had one or more 68Ga-PSMA-11-positive primary prostate
      lesions. Twenty-five (34%) and 7 (9.5%) of the 73 patients had 68Ga-PSMA-11
      positive pelvic LN and distant metastases, respectively. The sites of LN
      metastases in decreasing order of frequency were external iliac (20.5%), common
      iliac (13.5%), internal iliac (12.5%) obturator (12.5%), perirectal (4%),
      abdominal (4%), upper diaphragm (4%), and presacral (1.5%). The median size of
      the LN lesions was 6 mm (range, 4-24 mm). RT planning based on the CTVs covered
      69 (94.5%) of the 73 primary lesions and 20 (80%) of the 25 pelvic LN lesions, on
      a per-patient analysis. Conclusion: 68Ga-PSMA-11 PET/CT had a major impact on
      intended definitive RT planning for PCa in 12 (16.5%) of the 73 patients whose RT
      fields covered the prostate, seminal vesicles, and pelvic LNs and in 25 (37%) of
      the 66 patients whose RT fields covered the prostate and seminal vesicles but not
      the pelvic LNs.

PMID- 29653979
TI  - 18F-FDG PET Response of Skeletal (Bone Marrow and Bone) Involvement After
      Induction Chemotherapy in Pediatric Hodgkin Lymphoma: Are Specific Response
      Criteria Required?
AB  - To determine whether the current 18F-FDG PET response criterion for skeletal
      involvement in Hodgkin lymphoma (HL) is suitable, we performed a systematic
      evaluation of the different types of skeletal involvement and their response on
      PET after 2 cycles of chemotherapy (PET-2). A secondary objective was to observe
      the influence of the initial uptake intensity (measured as qPET) and initial
      metabolic tumor volume (MTV) of skeletal lesions on the PET-2 response. Methods:
      The initial PET scans of 1,068 pediatric HL patients from the EuroNet-PHL-C1
      trial were evaluated for skeletal involvement by central review. Three types of
      skeletal lesions were distinguished: PET-only lesions (those detected on PET
      only), bone marrow (BM) lesions (as confirmed by MRI or BM biopsy), and bone
      lesions. qPET and MTV were calculated for each skeletal lesion. All PET-2 scans
      were assessed for residual tumor activity. The rates of complete metabolic
      response for skeletal and nodal involvement on PET-2 were compared. Results: Of
      the 1,068 patients, 139 (13%) showed skeletal involvement (44 PET-only, 32 BM,
      and 63 bone). Of the 139 patients with skeletal involvement, 101 (73%) became PET
      2-negative in the skeleton and 94 (68%) became PET-2-negative in the lymph nodes.
      The highest number of PET-2-negative scans in the skeleton was 42 (95%) in the 44
      PET-only patients, followed by 22 skeletal lesions (69%) in the 32 BM patients
      and 37 (59%) in the 63 bone patients. Lesions that became PET-2-negative showed a
      lower initial median qPET (2.74) and MTV (2 cm3) than lesions that remained PET-2
      positive (3.84 and 7 cm3, respectively). Conclusion: In this study with pediatric
      HL patients, the complete response rate for skeletal involvement on PET-2 was
      similar to that for nodal involvement. Bone flare seemed to be irrelevant.
      Overall, the current skeletal PET response criterion-comparison with the local
      skeletal background-is well suited. The initial qPET and MTV of skeletal lesions
      were predictive of the PET-2 result. Higher values for both parameters were
      associated with a worse PET-2 response.

PMID- 29653980
TI  - Controversial Issues in Thyroid Cancer Management.
AB  - The lack of prospective randomized clinical trials for most management topics in
      differentiated thyroid cancer forces us to make management recommendations based
      on retrospective observational data, which are often incomplete, subject to
      selection bias, and conflicting. Therefore, it is not surprising that many
      aspects of thyroid cancer management remain controversial and not well defined.
      This review will examine the controversies surrounding 3 important topics in
      thyroid cancer management: the option of thyroid lobectomy as initial therapy,
      the use of preoperative neck imaging to optimize the completeness of the initial
      surgery, and the selective use of radioactive iodine for remnant ablation,
      adjuvant treatment, or treatment for known persistent or recurrent disease. As
      thyroid cancer management moves toward a much more risk-adapted approach to
      personalized recommendations, clinicians and patients must balance the risks and
      benefits of the potential options to arrive at a plan that is optimized regarding
      both patient preferences/values and the philosophy/experience of the local
      disease management team.

PMID- 29653982
TI  - Introduction of Genetically Modified CD3zeta Improves Proliferation and
      Persistence of Antigen-Specific CTLs.
AB  - The clinical efficacy of T-cell therapies based on T cells transduced with genes
      encoding tumor-specific T-cell receptors (TCR-T) is related to the in vivo
      persistence of the T cells. To improve persistence without modifying TCR
      affinity, we instead modified intracellular signaling, using artificial T cell
      activating adapter molecules (ATAM), generated by inserting the intracellular
      domain (ICD) of activating T-cell signaling moieties into CD3zeta. ATAMs with the
      ICD of either CD28 or 4-1BB were generated, assembled into the TCR complex as a
      part of CD3zeta, and enhanced downstream signaling from the supramolecular
      activation cluster. ATAMs were retrovirally introduced into human CMV-specific or
      NY-ESO-1-specific TCR-transduced CD8+ T lymphocytes, and downstream functionality
      was then examined. ATAM-transduced NY-ESO-1 TCR-T cells were also investigated
      using the U266-xenograft mouse model. ATAMs were successfully transduced and
      localized to the cell membrane. ATAM-transduced CMV-specific T cells retained
      their cytotoxic activity and cytokine production against peptide-pulsed target
      cells without altering antigen-specificity and showed resistance to activation
      induced cell death. Upon both single and repeated stimulation, CD3zeta/4-1BB
      transduced T cells had superior proliferation to the CD3zeta-transduced T cells
      in both the CMV-specific and the NY-ESO-1 TCR-T models and significantly improved
      antitumor activity compared with untransduced T cells both in vitro and in a
      mouse xenograft model. ATAM-transduced TCR-T cells demonstrated improved
      proliferation and persistence in vitro and in vivo This strategy to control the
      intracellular signaling of TCR-T cells by ATAM transduction in combination with
      various tumor-specific TCRs may improve the efficacy of TCR-T therapy. Cancer
      Immunol Res; 6(6); 733-44. (c)2018 AACR.

PMID- 29653981
TI  - IL17A Regulates Tumor Latency and Metastasis in Lung Adeno and Squamous SQ.2b and
      AD.1 Cancer.
AB  - Somatic mutations can promote malignant transformation of airway epithelial cells
      and induce inflammatory responses directed against resultant tumors. Tumor
      infiltrating T lymphocytes (TIL) in early-stage non-small cell lung cancer
      (NSCLC) secrete distinct proinflammatory cytokines, but the contribution of these
      TILs to tumor development and metastasis remains unknown. We show here that TILs
      in early-stage NSCLC are biased toward IL17A expression (Th17) when compared with
      adjacent tumor-free tissue, whereas Th17 cells are decreased in tumor
      infiltrating locoregional lymph nodes in advanced NSCLC. Mice in which Pten and
      Smad4 (Pts4d/d ) are deleted from airway epithelial cells develop spontaneous
      tumors, that share genetic signatures with squamous- (SQ.2b), and adeno- (AD.1)
      subtypes of human NSCLC. Pts4d/d mice globally lacking in IL17a (Pts4d/dIl17a-/-
      ) showed decreased tumor latency and increased metastasis. Th17 cells were
      required for recruitment of CD103+ dendritic cells, and adoptive transfer of
      IL17a-sufficient CD4+ T cells reversed early tumor development and metastasis in
      Pts4d/dIl17a-/- mice. Together, these findings support a key role for Th17 cells
      in TILs associated with the Pts4d/d model of NSCLC and suggest therapeutic and
      biomarker strategies for human SQ2b and AD1 lung cancer. Cancer Immunol Res;
      6(6); 645-57. (c)2018 AACR.

PMID- 29653983
TI  - Caspase-1 from Human Myeloid-Derived Suppressor Cells Can Promote T Cell
      Independent Tumor Proliferation.
AB  - Immunosuppressive myeloid-derived suppressive cells (MDSCs) are characterized by
      their phenotypic and functional heterogeneity. To better define their T cell
      independent functions within the tumor, sorted monocytic CD14+CD11b+HLA-DRlow/-
      MDSCs (mMDSC) from squamous cell carcinoma patients showed upregulated caspase-1
      activity, which was associated with increased IL1beta and IL18 expression. In
      vitro studies demonstrated that mMDSCs promoted caspase-1-dependent proliferation
      of multiple squamous carcinoma cell lines in both human and murine systems. In
      vivo, growth rates of B16, MOC1, and Panc02 were significantly blunted in
      chimeric mice adoptively transferred with caspase-1 null bone marrow cells under
      T cell-depleted conditions. Adoptive transfer of wild-type Gr-1+CD11b+ MDSCs from
      tumor-bearing mice reversed this antitumor response, whereas caspase-1 inhibiting
      thalidomide-treated MDSCs phenocopied the antitumor response found in caspase-1
      null mice. We further hypothesized that MDSC caspase-1 activity could promote
      tumor-intrinsic MyD88-dependent carcinogenesis. In mice with wild-type caspase-1,
      MyD88-silenced tumors displayed reduced growth rate, but in chimeric mice with
      caspase-1 null bone marrow cells, MyD88-silenced tumors did not display
      differential tumor growth rate. When we queried the TCGA database, we found that
      caspase-1 expression is correlated with overall survival in squamous cell
      carcinoma patients. Taken together, our findings demonstrated that caspase-1 in
      MDSCs is a direct T cell-independent mediator of tumor proliferation. Cancer
      Immunol Res; 6(5); 566-77. (c)2018 AACR.

PMID- 29653984
TI  - "Sinking into a coma" from spontaneous intracranial hypotension.

PMID- 29653985
TI  - Functional movement disorders arising after successful deep brain stimulation.

PMID- 29653986
TI  - Coma: A serious complication of spontaneous intracranial hypotension.
AB  - OBJECTIVE: To review our experience with patients with spontaneous intracranial
      hypotension (SIH) and coma because, although disorders of consciousness may
      complicate SIH, no comprehensive study of such patients has been reported.
      METHODS: Using a prospectively maintained registry, we identified all patients
      with SIH in whom coma developed. Patients or their caregivers/families were
      contacted for follow-up. Patients were compared to a cohort of patients with SIH
      without coma. RESULTS: The mean age of the 12 men and 3 women with SIH was 56.2
      years (range 34-72 years) at the time of onset of coma. In one-third of patients,
      coma developed after craniotomy for subdural hematomas or for an unrelated
      intracranial pathology. Imaging showed brain sagging, including bilateral
      temporal lobe herniation, in all 15 patients and brainstem edema in 8 patients
      (53%). Overall, coma was reversible in 7 of 15 patients treated with epidural
      blood patches, in 2 of 4 treated with percutaneous glue injections, and in 6 of 6
      treated surgically. Only 1 patient had residual neurologic deficit related to
      coma (Glasgow Outcome Scale score 4 [moderate disability]). Compared to patients
      with SIH without coma (n = 568), those with coma were older, more often were
      male, and more often underwent surgery. CONCLUSIONS: Coma in SIH is rare,
      reversible, and invariably associated with brain sagging. Coma due to SIH may be
      refractory to the usual percutaneous procedures, and surgical closure of the CSF
      leak may be required to regain consciousness.

PMID- 29653988
TI  - Glial fibrillary acid protein: Functions and involvement in disease.

PMID- 29653987
TI  - Prevalence of preclinical Alzheimer disease: Comparison of current classification
      systems.
AB  - OBJECTIVE: To determine the prevalence of preclinical Alzheimer disease (AD)
      according to current classification systems by examining CSF from a
      representative general population sample of 70-year-olds from Gothenburg, Sweden.
      METHOD: The sample was derived from the population-based H70 Gothenburg Birth
      Cohort Studies in Gothenburg, Sweden. The participants (n = 322, age 70 years)
      underwent comprehensive neuropsychiatric, cognitive, and somatic examinations.
      CSF levels of beta-amyloid (Abeta)42, Abeta40, total tau, and phosphorylated tau
      were measured. Preclinical AD was classified according to criteria of the A/T/N
      system, Dubois 2016, National Institute on Aging-Alzheimer's Association (NIA-AA)
      criteria, and International Working Group-2 (IWG-2) criteria. Individuals with
      Clinical Dementia Rating score >0 were excluded, leaving 259 cognitively
      unimpaired individuals. RESULTS: The prevalence of amyloid pathology was 22.8%,
      of total tau pathology was 33.2%, and of phosphorylated tau pathology was 6.9%.
      With the A/T/N system, the prevalence of A+/T-/N- was 13.1%, A+/T-/N+ was 7.3%,
      A+/T+/N+ was 2.3%, A-/T-/N+ was 18.9%, and A-/T+/N+ was 4.6%. When the Dubois
      criteria were applied, the prevalence of asymptomatic at risk for AD was 36.7%
      and of preclinical AD was 9.7%. With the NIA-AA criteria, the prevalence of stage
      1 was 13.1% and stage 2 was 9.7%. With the IWG-2 criteria, the prevalence of
      asymptomatic at risk for AD was 9.7%. The APOE epsilon4 allele was associated
      with several of the categories. Men more often had total tau pathology, A+/T-/N+,
      preclinical AD according to Dubois 2016, asymptomatic at risk for AD according to
      the IWG-2 criteria, and NIA-AA stage 2. CONCLUSION: The prevalence of pathologic
      AD markers was very common (46%) in a representative population sample of 70-year
      olds. The clinical implications of these findings need to be scrutinized further
      in longitudinal studies.

PMID- 29653989
TI  - A pilot educational intervention for headache and concussion: The headache and
      arts program.
AB  - OBJECTIVE: Using a science, technology, engineering, arts, and mathematics
      (STEAM) curriculum, we developed, piloted, and tested the Headache and Arts
      Program. This program seeks to increase knowledge and awareness of migraine and
      concussion among high school students through a visual arts-based curriculum.
      METHODS: We developed a 2-week Headache and Arts Program with lesson plans and
      art assignments for high school visual arts classes and an age-appropriate
      assessment to assess students' knowledge of migraine and concussion. We assessed
      students' knowledge through (1) the creation of artwork that depicted the
      experience of a migraine or concussion, (2) the conception and implementation of
      methods to transfer knowledge gained through the program, and (3) preassessment
      and postassessment results. The assessment was distributed to all students prior
      to the Headache and Arts Program. In a smaller sample, we distributed the
      assessment 3 months after the program to assess longitudinal effects. Descriptive
      analyses and p values were calculated using SPSS V.24 and Microsoft Excel.
      RESULTS: Forty-eight students participated in the research program. Students
      created artwork that integrated STEAM knowledge learned through the program and
      applied creative methods to teach others about migraine and concussion. At
      baseline, students' total scores averaged 67.6% correct. Total scores for the
      longitudinal preassessment, immediate postassessment, and delayed 3-month
      postassessment averaged 69.4%, 72.8%, and 80.0% correct, respectively.
      CONCLUSION: The use of a visual arts-based curriculum may be effective for
      migraine and concussion education among high school students.

PMID- 29653990
TI  - Neurofilament light and tau as blood biomarkers for sports-related concussion.
AB  - OBJECTIVE: To compare neurofilament light (NfL) and tau as blood-based biomarkers
      for acute sports-related concussion (SRC) and determine whether their
      concentrations at different time points after the injury are associated with
      prolonged time to return to play (RTP). METHODS: A total of 288 professional
      hockey players were followed longitudinally from September 1, 2012, to April 30,
      2015. Data collection and biomarker analyses were conducted between 2015 and
      2017. Associations were tested between blood concentrations of NfL and tau, and
      RTP time. Serum concentrations of S100B and neuron-specific enolase (NSE) were
      also measured for comparison. RESULTS: Of 288 players, 105 sustained an SRC. Of
      these, 87 underwent blood sampling 1, 12, 36, and 144 hours after SRC and at the
      RTP time point. Serum NfL concentrations 1, 12, 36, and 144 hours after SRC were
      related to prolonged RTP time, and could separate players with RTP >10 days from
      those with RTP <=10 days (area under the receiver operating characteristic curve
      [AUROC] 0.82). Also, serum NfL 144 hours after SRC discriminated players who
      resigned from the game due to persistent postconcussion symptoms (PCS) from those
      who returned to play (AUROC 0.89). Plasma tau 1 hour after SRC was related to RTP
      but less strongly than NfL, while S100B and NSE showed no such associations.
      CONCLUSION: Serum NfL outperformed tau, S100B, and NSE as a biomarker for SRC.
      From a clinical standpoint, serum NfL may be useful to identify individuals at
      risk of prolonged PCS, and may aid in biomarker-informed decisions with regard to
      when RTP should be considered.

PMID- 29653991
TI  - Mediterranean diet and 3-year Alzheimer brain biomarker changes in middle-aged
      adults.
AB  - OBJECTIVE: To examine in a 3-year brain imaging study the effects of higher vs
      lower adherence to a Mediterranean-style diet (MeDi) on Alzheimer disease (AD)
      biomarker changes (brain beta-amyloid load via 11C-Pittsburgh compound B [PiB]
      PET and neurodegeneration via 18F-fluorodeoxyglucose [FDG] PET and structural
      MRI) in midlife. METHODS: Seventy 30- to 60-year-old cognitively normal
      participants with clinical, neuropsychological, and dietary examinations and
      imaging biomarkers at least 2 years apart were examined. These included 34
      participants with higher (MeDi+) and 36 with lower (MeDi-) MeDi adherence.
      Statistical parametric mapping and volumes of interest were used to compare AD
      biomarkers between groups at cross section and longitudinally. RESULTS: MeDi
      groups were comparable for clinical and neuropsychological measures. At baseline,
      compared to the MeDi+ group, the MeDi- group showed reduced FDG-PET glucose
      metabolism (CMRglc) and higher PiB-PET deposition in AD-affected regions (p <
      0.001). Longitudinally, the MeDi--group showed CMRglc declines and PiB increases
      in these regions, which were greater than those in the MeDi+ group (pinteraction
      < 0.001). No effects were observed on MRI. Higher MeDi adherence was estimated to
      provide 1.5 to 3.5 years of protection against AD. CONCLUSION: Lower MeDi
      adherence was associated with progressive AD biomarker abnormalities in middle
      aged adults. These data support further investigation of dietary interventions
      for protection against brain aging and AD.

PMID- 29653992
TI  - A multicenter examination and strategic revisions of the Yale Global Tic Severity
      Scale.
AB  - OBJECTIVE: To examine the internal consistency and distribution of the Yale
      Global Tic Severity Scale (YGTSS) scores to inform modification of the measure.
      METHODS: This cross-sectional study included 617 participants with a tic disorder
      (516 children and 101 adults), who completed an age-appropriate diagnostic
      interview and the YGTSS to evaluate tic symptom severity. The distributions of
      scores on YGTSS dimensions were evaluated for normality and skewness. For
      dimensions that were skewed across motor and phonic tics, a modified Delphi
      consensus process was used to revise selected anchor points. RESULTS: Children
      and adults had similar clinical characteristics, including tic symptom severity.
      All participants were examined together. Strong internal consistency was
      identified for the YGTSS Motor Tic score (alpha = 0.80), YGTSS Phonic Tic score
      (alpha = 0.87), and YGTSS Total Tic score (alpha = 0.82). The YGTSS Total Tic and
      Impairment scores exhibited relatively normal distributions. Several subscales
      and individual item scales departed from a normal distribution. Higher scores
      were more often used on the Motor Tic Number, Frequency, and Intensity dimensions
      and the Phonic Tic Frequency dimension. By contrast, lower scores were more often
      used on Motor Tic Complexity and Interference, and Phonic Tic Number, Intensity,
      Complexity, and Interference. CONCLUSIONS: The YGTSS exhibits good internal
      consistency across children and adults. The parallel findings across Motor and
      Phonic Frequency, Complexity, and Interference dimensions prompted minor
      revisions to the anchor point description to promote use of the full range of
      scores in each dimension. Specific minor revisions to the YGTSS Phonic Tic
      Symptom Checklist were also proposed.

PMID- 29653993
TI  - Synthetic control methodology as a tool for evaluating population-level health
      interventions.
AB  - BACKGROUND: Many public health interventions cannot be evaluated using randomised
      controlled trials so they rely on the assessment of observational data.
      Techniques for evaluating public health interventions using observational data
      include interrupted time series analysis, panel data regression-based approaches,
      regression discontinuity and instrumental variable approaches. The inclusion of a
      counterfactual improves causal inference for approaches based on time series
      analysis, but the selection of a suitable counterfactual or control area can be
      problematic. The synthetic control method builds a counterfactual using a
      weighted combination of potential control units. METHODS: We explain the
      synthetic control method, summarise its use in health research to date, set out
      its advantages, assumptions and limitations and describe its implementation
      through a case study of life expectancy following German reunification. RESULTS:
      Advantages of the synthetic control method are that it offers an approach
      suitable when there is a small number of treated units and control units and it
      does not rely on parallel preimplementation trends like difference in difference
      methods. The credibility of the result relies on achieving a good
      preimplementation fit for the outcome of interest between treated unit and
      synthetic control. If a good preimplementation fit is established over an
      extended period of time, a discrepancy in the outcome variable following the
      intervention can be interpreted as an intervention effect. It is critical that
      the synthetic control is built from a pool of potential controls that are similar
      to the treated unit. There is currently no consensus on what constitutes a 'good
      fit' or how to judge similarity. Traditional statistical inference is not
      appropriate with this approach, although alternatives are available. From our
      review, we noted that the synthetic control method has been underused in public
      health. CONCLUSIONS: Synthetic control methods are a valuable addition to the
      range of approaches for evaluating public health interventions when randomisation
      is impractical. They deserve to be more widely applied, ideally in combination
      with other methods so that the dependence of findings on particular assumptions
      can be assessed.

PMID- 29653994
TI  - Ideal cardiovascular health metrics and its association with 20-year
      cardiovascular morbidity and mortality in a Chinese population.
AB  - BACKGROUND: The American Heart Association (AHA) developed a simplified
      assessment tool based on seven ideal cardiovascular health (CVH) metrics, but the
      relationship between the AHA defined ideal CVH metrics and cardiovascular risk in
      Chinese population has not been well estimated. METHODS: The baseline survey were
      conducted among 938 Chinese men and women from four urban and rural population
      samples in China, aged 35-59 years in 1983-1984. The cohort was followed up for
      multiple cardiovascular endpoints up to 2005. Cox proportional hazard models were
      used to test the associations accounting for multiple covariates. Outcomes were
      collected in 1987-2005 and data analysed in 2017. RESULTS: During a median of
      20.3 years follow-up, 68 non-fatal CVD events and 139 deaths (29 CVD deaths)
      occurred. The multivariable adjusted HRs and 95% CIs for all CVD in the groups
      with three and 4-7 ideal CVH metrics were 0.59 (95% CI 0.33 to 1.04) and 0.24
      (95% CI 0.12 to 0.47), when the group with 0-2 ideal CVH metrics as the
      reference. Results also showed that participants with 4-7 ideal CVH metrics had a
      54% (95% CI 24% to 72%) lower risk of all-cause mortality in comparison with
      those with 0-2 ideal metrics. CONCLUSIONS: The number of ideal CVH metrics was
      inversely associated with the risk of cardiovascular morbidity and mortality in
      this Chinese general population.

PMID- 29653995
TI  - Light sheet imaging comes of age.
AB  - Light-sheet fluorescence microscopy methods that minimize photodamage are
      increasingly penetrant in biomedical research and currently comprise three
      distinct platforms. In this issue, Fadero et al. (2018. J. Cell Biol.
      https://doi.org/10.1083/jcb.201710087) describe a fourth approach termed "LITE
      microscopy," which is useful for extended imaging of specimens from cells to
      organisms.

PMID- 29653996
TI  - DNA replication licensing in stem cells: Gatekeeping the commitment to
      proliferation.
AB  - Carroll et al. (2018. J. Cell Biol. https://doi.org/10.1083/jcb.201708023)
      developed a method to assess DNA replication licensing in tissues. They show that
      intestinal stem cells within wild-type crypts, but not in crypts with cancer
      causing mutations, are largely unlicensed, suggesting that licensing may
      represent a rate-limiting step in the commitment to proliferation.

PMID- 29653997
TI  - Hsp40/70/110 chaperones adapt nuclear protein quality control to serve cytosolic
      clients.
AB  - Misfolded cytosolic proteins are degraded by the ubiquitin proteasome system
      through quality control (QC) pathways defined by E3 ubiquitin ligases and
      associated chaperones. Although they work together as a comprehensive system to
      monitor cytosolic protein folding, their respective contributions remain unclear.
      To bridge existing gaps, the pathways mediated by the San1 and Ubr1 E3 ligases
      were studied coordinately. We show that pathways share the same complement of
      chaperones needed for substrate trafficking, ubiquitination, and degradation. The
      significance became clear when Ubr1, like San1, was localized primarily to the
      nucleus. Appending nuclear localization signals to cytosolic substrates revealed
      that Ydj1 and Sse1 are needed for substrate nuclear import, whereas Ssa1/Ssa2 is
      needed both outside and inside the nucleus. Sis1 is required to process all
      substrates inside the nucleus, but its role in trafficking is substrate specific.
      Together, these data show that using chaperones to traffic misfolded cytosolic
      proteins into the nucleus extends the nuclear protein QC pathway to include
      cytosolic clients.

PMID- 29653998
TI  - Association Between Early Outpatient Visits and Readmissions After Ischemic
      Stroke.
AB  - BACKGROUND: Reducing hospital readmission is an important goal to optimize
      poststroke care and reduce costs. Early outpatient follow-up may represent one
      important strategy to reduce readmissions. We examined the association between
      time to first outpatient contact and readmission to inform postdischarge
      transitions. METHODS AND RESULTS: We performed a retrospective cohort study of
      all Medicare fee-for-service patients discharged home after an acute ischemic
      stroke in 2012 identified by the InternationalClassification of Diseases, Ninth
      Revision, Clinical Modification codes. Our primary predictor variable was whether
      patients had a primary care or neurology visit within 30 days of discharge. Our
      primary outcome variable was all-cause 30-day hospital readmission. We used
      separate multivariable Cox models with primary care and neurology visits
      specified as time-dependent covariates, adjusted for numerous patient- and
      systems-level factors. The cohort included 78 345 patients. Sixty-one percent and
      16% of patients, respectively, had a primary care and neurology visit within 30
      days of discharge. Visits occurred a median (interquartile range) 7 (4-13) and 15
      (5-22) days after discharge for primary care and neurology, respectively. Thirty
      day readmission occurred in 9.4% of patients. Readmissions occurred a median 14
      (interquartile range, 7-21) days after discharge. Patients who had a primary care
      visit within 30 days of discharge had a slightly lower adjusted hazard of
      readmission than those who did not (hazard ratio, 0.98; 95% confidence interval,
      0.97-0.98). The association was nearly identical for 30-day neurology visits
      (hazard ratio, 0.98; 95% confidence interval, 0.97-0.98). CONCLUSIONS: Thirty-day
      outpatient follow-up was associated with a small reduction in hospital
      readmission among elderly patients with stroke discharged home. Further work
      should assess how outpatient care may be improved to further reduce readmissions.

PMID- 29653999
TI  - Clinical Events After Discontinuation of beta-Blockers in Patients Without Heart
      Failure Optimally Treated After Acute Myocardial Infarction: A Cohort Study on
      the French Healthcare Databases.
AB  - BACKGROUND: beta-blockers have been among the first medications shown to improve
      outcomes after acute myocardial infarction (AMI). With the advent of reperfusion
      therapy and other secondary-prevention medications, their role has become
      uncertain, and large-scale experience after AMI in the contemporary era is
      lacking. In particular, the effect of stopping beta-blockers in patients
      initially treated after AMI is unknown. METHODS AND RESULTS: Using the French
      healthcare databases, 73 450 patients (<80 years of age), admitted for AMI in
      2007 to 2012, without acute coronary syndrome (ACS) in the previous 2 years and
      no evidence of heart failure, having received optimal treatment with myocardial
      revascularization and all recommended medications in the 4 months after index
      admission, and not having discontinued beta-blockers before 1 year, were followed
      for 3.8 years on average. beta-Blocker discontinuation was defined as 4
      consecutive months without exposure. If beta-blocker treatment was resumed later
      on, follow-up was stopped. Both the risk of the composite outcome of death or
      admission for ACS and the risk of all-cause mortality were assessed in relation
      with beta-blocker discontinuation during follow-up. Adjusted hazard ratios were
      estimated using marginal structural models accounting for time-varying
      confounders affected by previous exposure. A similar analysis was performed with
      statins. Of 204 592 patient-years, 12 002 (5.9%) corresponded to discontinued
      beta-blocker treatment. For beta-blocker discontinuation, the adjusted hazard
      ratio for death or ACS was 1.17 (95% confidence interval, 1.01-1.35); for all
      cause death, the adjusted hazard ratio was 1.13 (95% confidence interval, 0.94
      1.36). In contrast, for statin discontinuation, the adjusted hazard ratios for
      death or ACS and for all-cause death were 2.31 (95% confidence interval, 2.01
      2.65) and 2.57 (95% confidence interval, 2.19-3.02), respectively. CONCLUSIONS:
      In routine care of patients without heart failure, revascularized and optimally
      treated after AMI, discontinuation of beta-blockers beyond 1 year after AMI was
      associated with an increased risk of death or readmission for ACS, while
      statistical significance was not reached for the association with all-cause
      mortality. A contemporary randomized clinical trial is needed to precise the role
      of beta-blockers in the long-term treatment after AMI.

PMID- 29654000
TI  - Value-Based ST-Segment-Elevation Myocardial Infarction Care Using Risk-Guided
      Triage and Early Discharge.
AB  - BACKGROUND: Prior studies suggest that low-risk ST-segment-elevation myocardial
      infarction (STEMI) patients undergoing primary percutaneous coronary intervention
      can be considered for early discharge. We describe the implementation of an STEMI
      risk score to decrease cost while maintaining optimal patient outcomes. METHODS
      AND RESULTS: We determined the impact of risk-guided STEMI care on healthcare
      value through the retrospective application of the Zwolle Risk Score to 967
      patients receiving primary percutaneous coronary intervention between 2009 and
      2011. Of these patients, 540 (56%) were categorized as low risk, indicating they
      may be safely triaged directly to a telemetry unit rather than the intensive care
      unit and targeted for early discharge. We subsequently developed and implemented
      a modified Zwolle Risk Calculator into the electronic medical record to support
      application of the fast-track protocol for low-risk STEMI patients. Among 549
      prospective patients with STEMI, 62% were low risk, and the fast-track protocol
      was followed in 75% of cases. Prospective results confirmed lower rates of
      complications (low risk 8.3% versus high risk 38.7%; P<0.001) and in-hospital
      mortality (low risk 0.4% versus High risk 12.5%; P<0.001) in the low-risk cohort.
      Low-risk patients had a shorter median length of stay (median and [25th, 75th
      percentiles]: low risk 2 [2, 3] versus high risk: 3 [2, 6]; P<0.001) and lower
      overall costs (low risk $6720 [$5280-$9030] versus high risk $11 783 [$7953-$25
      359]; P<0.001). Low-risk patients treated on-protocol had shorter median length
      of stay (on-protocol 2 [1, 2] versus off-protocol 2 [2, 3]; P<0.001) and hospital
      costs (on-protocol $6090 [$4730, $7356] versus off-protocol $11 783 [$7953, $25
      359]; P<0.001) than those treated off-protocol. On-protocol low-risk patients in
      the prospective cohort also had lower costs and shorter length of stay than low
      risk patients in the retrospective cohort (P<0.001 for both). CONCLUSIONS: In our
      study, risk-guided triage and discharge after primary percutaneous coronary
      intervention for STEMI improved healthcare value by reducing costs of care
      without compromising quality of care or patient outcomes.

PMID- 29654001
TI  - Overtreatment or Undertreatment of Carotid Disease: A Transatlantic Comparison of
      Carotid Endarterectomy Patient Cohorts.

PMID- 29654002
TI  - Stopping beta-Blockers After Myocardial Infarction: Not So Fast!

PMID- 29654003
TI  - Is the weekend effect really ubiquitous? A retrospective clinical cohort analysis
      of 30-day mortality by day of week and time of day using linked population data
      from New South Wales, Australia.
AB  - OBJECTIVE: To examine the associations between day of week and time of admission
      and 30-day mortality for six clinical conditions: ischaemic and haemorrhagic
      stroke, acute myocardial infarction, pneumonia, chronic obstructive pulmonary
      disease and congestive heart failure. DESIGN: Retrospective population-based
      cohort analyses. Hospitalisation records were linked to emergency department and
      deaths data. Random-effect logistic regression models were used, adjusting for
      casemix and taking into account clustering within hospitals. SETTING: All
      hospitals in New South Wales, Australia, from July 2009 to June 2012.
      PARTICIPANTS: Patients admitted to hospital with a primary diagnosis for one of
      the six clinical conditions examined. OUTCOME MEASURES: Adjusted ORs for all
      cause mortality within 30 days of admission, by day of week and time of day.
      RESULTS: A total of 148 722 patients were included in the study, with 17 721
      deaths within 30 days of admission. Day of week of admission was not associated
      with significantly higher likelihood of death for five of the six conditions
      after adjusting for casemix. There was significant variation in mortality for
      chronic obstructive pulmonary disease by day of week; however, this was not
      consistent with a strict weekend effect (Thursday: OR 1.29, 95% CI 1.12 to 1.48;
      Friday: OR 1.25, 95% CI 1.08 to 1.44; Saturday: OR 1.18, 95% CI 1.02 to 1.37;
      Sunday OR 1.05, 95% CI 0.90 to 1.22; compared with Monday). There was evidence
      for a night effect for patients admitted for stroke (ischaemic: OR 1.30, 95% CI
      1.17 to 1.45; haemorrhagic: OR 1.58, 95% CI 1.40 to 1.78). CONCLUSIONS: Mortality
      outcomes for these conditions, adjusted for casemix, do not vary in accordance
      with the weekend effect hypothesis. Our findings support a growing body of
      evidence that questions the ubiquity of the weekend effect.

PMID- 29654004
TI  - What is the quality of the maternal near-miss case reviews in WHO European
      Region? Cross-sectional study in Armenia, Georgia, Latvia, Republic of Moldova
      and Uzbekistan.
AB  - OBJECTIVES: The maternal near-miss case review (NMCR) cycle is a type of clinical
      audit aiming at improving quality of maternal healthcare by discussing near-miss
      cases. In several countries this approach has been introduced and supported by
      WHO and partners since 2004, but information on the quality of its implementation
      is missing. This study aimed at evaluating the quality of the NMCR implementation
      in selected countries within WHO European Region. DESIGN: Cross-sectional study.
      SETTINGS: Twenty-three maternity units in Armenia, Georgia, Latvia, Moldova and
      Uzbekistan. ASSESSMENT TOOLS: A predefined checklist including 50 items,
      according to WHO methodology. Quality in the NMCR implementation was defined by
      summary scores ranging from 0 (totally inappropriate) to 3 (appropriate).
      RESULTS: Quality of the NMCR implementation was heterogeneous among different
      countries, and within the same country. Overall, the first part of the audit
      cycle (from case identification to case analysis) was fairly well performed (mean
      score 2.00, 95% CI 1.94 to 2.06), with the exception of the 'inclusion of users'
      views' (mean score 0.66, 95% CI 0.11 to 1.22), while the second part (developing
      recommendations, implementing them and ensuring quality) was poorly performed
      (mean score 0.66, 95% CI 0.11 to 1.22). Each country had at least one champion
      facility, where quality of the NMCR cycle was acceptable. Quality of the
      implementation was not associated with its duration. Gaps in implementation were
      of technical, organisational and attitudinal nature. CONCLUSIONS: Ensuring
      quality in the NMCR may be difficult but achievable. The high heterogeneity in
      results within the same country suggests that quality of the NMCR implementation
      depends, to a large extent, from hospital factors, including staff's commitment,
      managerial support and local coordination. Efforts should be put in preventing
      and mitigating common barriers that hamper successful NMCR implementation.

PMID- 29654005
TI  - Is ambient air pollution associated with onset of sudden infant death syndrome: a
      case-crossover study in the UK.
AB  - OBJECTIVES: Air pollution has been associated with increased mortality and
      morbidity in several studies with indications that its effect could be more
      severe in children. This study examined the relationship between short-term
      variations in criteria air pollutants and occurrence of sudden infant death
      syndrome (SIDS). DESIGN: We used a case-crossover study design which is widely
      applied in air pollution studies and particularly useful for estimating the risk
      of a rare acute outcome associated with short-term exposure. SETTING: The study
      used data from the West Midlands region in the UK. PARTICIPANTS: We obtained
      daily time series data on SIDS mortality (ICD-9: 798.0 or ICD-10: R95) for the
      period 1996-2006 with a total of 211 SIDS events. PRIMARY OUTCOME MEASURES: Daily
      counts of SIDS events. RESULTS: For an IQR increase in previous day pollutant
      concentration, the percentage increases (95% CI) in SIDS were 16 (6 to 27) for
      PM10, 1 (-7 to 10) for SO2, 5 (-4 to 14) for CO, -17 (-27 to -6) for O3, 16 (2 to
      31) for NO2 and 2 (-3 to 8) for NO after controlling for average temperature and
      national holidays. PM10 and NO2 showed relatively consistent association which
      persisted across different lag structures and after adjusting for copollutants.
      CONCLUSIONS: The results indicated ambient air pollutants, particularly PM10 and
      NO2, may show an association with increased SIDS mortality. Thus, future studies
      are recommended to understand possible mechanistic explanations on the role of
      air pollution on SIDS incidence and the ways in which we might reduce pollution
      exposure among infants.

PMID- 29654006
TI  - Does bone mineral density improve the predictive accuracy of fracture risk
      assessment? A prospective cohort study in Northern Denmark.
AB  - OBJECTIVE: To evaluate the added predictive accuracy of bone mineral density
      (BMD) to fracture risk assessment. DESIGN: Prospective cohort study using data
      between 01 January 2010 and 31 December 2012. SETTING: North Denmark Osteoporosis
      Clinic of referred patients presenting with at least one fracture risk factor to
      the referring doctor. PARTICIPANTS: Patients aged 40-90 years; had BMD T-score
      recorded at the hip and not taking osteoporotic preventing drugs for more than 1
      year prior to baseline. MAIN OUTCOME MEASURES: Incident diagnoses of osteoporotic
      fractures (hip, spine, forearm, humerus and pelvis) were identified using the
      National Patient Registry of Denmark during 01 January 2012-01 January 2014. Cox
      regression was used to develop a fracture model based on predictors in the
      Fracture Risk Assessment Tool (FRAX(r)), with and without, binary and continuous
      BMD. Change in Harrell's C-Index and Reclassification tables were used to
      describe the added statistical value of BMD. RESULTS: Adjusting for predictors
      included in FRAX(r), patients with osteoporosis (T-score <=-2.5) had 75% higher
      hazard of a fracture compared with patients with higher BMD (HR: 1.75 (95% CI
      1.28 to 2.38)). Forty per cent lower hazard was found per unit increase in
      continuous BMD T-score (HR: 0.60 (95% CI 0.52 to 0.69)).Accuracy improved
      marginally, and Harrell's C-Index increased by 1.2% when adding continuous BMD
      (0.76 to 0.77). Reclassification tables showed continuous BMD shifted 529
      patients into different risk categories; 292 of these were reclassified correctly
      (57%; 95% CI 55% to 64%). Adding binary BMD however no improvement: Harrell's C
      Index decreased by 0.6%. CONCLUSIONS: Continuous BMD marginally improves fracture
      risk assessment. Importantly, this was only found when using continuous BMD
      measurement for osteoporosis. It is suggested that future focus should be on
      evaluation of this risk factor using routinely collected data and on the
      development of more clinically relevant methodology to assess the added value of
      a new risk factor.

PMID- 29654007
TI  - Pleasure and practice: a qualitative study of the individual and social
      underpinnings of shisha use in cafes among youth in the UK.
AB  - OBJECTIVES: To explore (1) the social function of shisha cafes for young people
      living in the UK and (2) other alternative activities (existing or potential)
      that do not involve tobacco smoking. METHODS: We conducted qualitative interviews
      with young adults (age 18-30) in Leeds, UK. Snowballing sampling was used in
      selecting the participants. Interviews were audio-recorded and explored the
      perspectives and experiences of young people in as well as potential alternative
      activities. Data were transcribed and analysed thematically. RESULTS: Shisha use
      plays a central role in social interactions. Youth described using shisha because
      of emotional and sensory pleasure. Shisha use was implicitly endorsed by
      respected professionals, such as doctors and university lecturers, who were seen
      smoking it. Most, but not all, shisha smokers acknowledged that shisha use is
      harmful. Suggestions for reducing shisha use included use of non- tobacco
      alternatives, legislation to reduce access and alternative means for socialising,
      such as sports. CONCLUSION: For young people in the UK, the known health dangers
      of shisha are outweighed by its social benefits and shisha is perceived as
      acceptable. Interventions to reverse the increase in shisha cafes should focus on
      both individual smoker as well as the community, without sacrificing the
      importance of social interactions.

PMID- 29654008
TI  - Cardiac implant registries 2006-2016: a systematic review and summary of global
      experiences.
AB  - OBJECTIVES: The importance of Cardiac Implant Registry (CIR) for ensuring a long
      term follow-up in postmarket surveillance has been recognised and approved, but
      there is lack of consensus standards on how to establish a CIR. The aim of this
      study is to investigate the structure and key elements of CIRs in the past decade
      (2006-2016) and to provide recommendations on 'best practice' approaches.
      SETTINGS AND PARTICIPANTS: A systematic search on CIR was employed in line with
      the Preferred Reporting Items for Systematic Reviews and Meta-Analyses
      guidelines. The following databases were searched: the PubMed (Medline),
      ScienceDirect and the Scopus database, EMBASE. After identifying the existing
      CIRs, an aggregative approach will be used to explore key elements emerging in
      the identified registries. RESULTS: The following 82 registries were identified:
      18 implantable cardioverterdefibrillator (ICD) registries, 7 cardiac
      resynchronisation therapy (CRT) registries, 5 pacemaker registries and 6
      cardiovascular implantable electronic device registries which combined ICD,
      pacemaker and CRT implantation data; as well as 22 coronary stent registries and
      24 transcatheteraortic heart valve implantation registries. While 71 national or
      local registries are from a single country, 44 are from European countries and 9
      are located in USA. The following criteria have been summarised from the
      identified registries, including: registry working group, ethic issues,
      transparency, research objective, inclusion criteria, compulsory participation,
      endpoint, sample size, data collection basement, data collection methods, data
      entry, data validation and statistical analysis. CONCLUSIONS: Registries provide
      a 'real-world' picture for patients, physicians, manufacturers, payers, decision
      makers and other stakeholders. CIRs are important for regulatory decisions
      concerning the safety and therefore approval issues of the medical device; for
      payers CIRs provide evidence on the medical device benefit and drive the decision
      whether the product should be reimbursed or not; for hospitals CIRs' data are
      important for sound procurement decisions, and CIRs also help patients and their
      physicians to joint decision-making which of the products is the most
      appropriate.

PMID- 29654009
TI  - Informational value of percent body fat with body mass index for the risk of
      abnormal blood glucose: a nationally representative cross-sectional study.
AB  - OBJECTIVE: To examine the value of percent body fat (%BF) with body mass index
      (BMI) to assess the risk of abnormal blood glucose (ABG) among US adults who are
      normal weight or overweight. We hypothesised that normal-weight population with
      higher %BF is more likely to have ABG. DESIGN: A cross-sectional study. SETTING:
      National Health and Nutrition Examination Survey, 1999-2006, conducted by the
      National Center for Health Statistics of the Centers for Disease Control and
      Prevention. PARTICIPANTS: Participants were US adults aged 40 and older who have
      never been diagnosed with type 2 diabetes by a doctor (unweighted n=6335,
      weighted n=65 705 694). The study population was classified into four groups: (1)
      normal weight with normal %BF, (2) normal weight with high %BF, (3) overweight
      with normal %BF and (4) overweight with high %BF. MAIN OUTCOME MEASURES: ORs for
      ABG including pre-diabetes and undiagnosed diabetes (HbA1c >=5.7%, >=39
      mmol/mol). RESULTS: 64% of population with normal BMI classification had a high
      %BF. Prevalence of ABG in normal-weight group with high %BF (13.5%) is
      significantly higher than the overweight group with low %BF (10.5%, P<0.001). In
      an unadjusted model, the OR of ABG was significantly greater in adults at normal
      BMI with high %BF compared with individuals at normal weight with low %BF. In an
      adjusted model controlling for age, sex, race/ethnicity, first-degree-relative
      diabetes, vigorous-intensity activities and muscle strengthening activities,
      risks of ABG were greater in population with normal weight and high %BF (OR 1.55,
      95% CI 1.01 to 2.38) and with overweight and low %BF (OR 1.17, 95% CI 0.69 to
      1.98, P<0.05). CONCLUSIONS: Integrating BMI with %BF can improve in
      classification to direct screening and prevention efforts to a group currently
      considered healthy and avoid penalties and stigmatisation of other groups that
      are classified as high risk of ABG.

PMID- 29654010
TI  - Association between human leucocyte antigen-DO polymorphisms and
      interferon/ribavirin treatment response in hepatitis C virus type 1 infection in
      Chinese population: a prospective study.
AB  - OBJECTIVE: The human leucocyte antigen-DO (HLA-DO) gene located in the HLA non
      classical class-II region may play a role in treatment response to hepatitis C
      virus (HCV). This study was conducted to explore the role of single nucleotide
      polymorphisms (SNPs) in HLA-DO in responding to HCV therapy. SETTING: All
      patients were recruited between January 2011 and September 2016 from the Jurong
      People's Hospital, Jiangsu Province, China. PARTICIPANTS: A total of 346 chronic
      hepatitis C (CHC) patients who finished the 48-week pegylated interferon-alpha
      and ribavirin (PEG IFN-alpha/RBV) treatment were enrolled in this study. All
      patients were former remunerated blood donors. The inclusion criteria for
      patients were as follows: (1) treatment-naive and treated with PEG IFN-alpha/RBV,
      (2) HCV RNA was present in serum for over 6 months before treatment, (3) negative
      for hepatitis B (HBV) or HIV infection and (4) lacked any other hepatic
      diseases.All participants in this study were Chinese Han population and infected
      with HCV genotype 1b and treated with subcutaneous PEG IFN-alpha at a dose of 180
      ug once a week with the addition of 800-1000 mg/d RBV according to weight orally
      for 48 weeks. RESULTS: The SNPs HLA-DOA rs1044429 and HLA-DOB rs2284191 and
      rs2856997 of 18 SNPs were correlated with HCV treatment response in the Chinese
      Han population. The dominant model indicated that patients carrying favourable
      genotypes at rs1044429 AA and rs2284191 AA were more likely to achieve sustained
      virological response (SVR) (OR 1.99, 95% CI 1.25 to 3.19; OR 2.71, 95% CI 1.58 to
      4.63, respectively), while patients carrying unfavourable genotypes at rs2856997
      GG were less likely to achieve SVR (OR 0.48, 95% CI 0.29 to 0.78). CONCLUSION:
      Genetic variations at rs1044429, rs2284191 and rs2856997 were independent
      predictors of HCV treatment response in the Chinese Han population.

PMID- 29654011
TI  - Development and validation of the Multimorbidity Treatment Burden Questionnaire
      (MTBQ).
AB  - OBJECTIVE: To develop and validate a new scale to assess treatment burden (the
      effort of looking after one's health) for patients with multimorbidity. DESIGN:
      Mixed-methods. SETTING: UK primary care. PARTICIPANTS: Content of the
      Multimorbidity Treatment Burden Questionnaire (MTBQ) was based on a literature
      review and views from a patient and public involvement group. Face validity was
      assessed through cognitive interviews. The scale was piloted and the final
      version was tested in 1546 adults with multimorbidity (mean age 71 years) who
      took part in the 3D Study, a cluster randomised controlled trial. For each
      question, we examined the proportion of missing data and the distribution of
      responses. Factor analysis, Cronbach's alpha, Spearman's rank correlations and
      longitudinal regression assessed dimensional structure, internal consistency
      reliability, construct validity and responsiveness, respectively. We assessed
      interpretability by grouping the global MTBQ scores into zero and tertiles (>0)
      and comparing participant characteristics across these categories. RESULTS:
      Cognitive interviews found good acceptability and content validity. Factor
      analysis supported a one-factor solution. Cronbach's alpha was 0.83, indicating
      internal consistency reliability. The MTBQ score had a positive association with
      a comparator treatment burden scale (rs 0.58, P<0.0001) and with self-reported
      disease burden (rs 0.43, P<0.0001), and a negative association with quality of
      life (rs-0.36, P<0.0001) and self-rated health (rs-0.36, P<0.0001). Female
      participants, younger participants and participants with mental health conditions
      were more likely to have high treatment burden scores. Changes in MTBQ score over
      9-month follow-up were associated, as expected, with changes in measures of
      quality of life (EuroQol five dimensions, five level questionnaire) and patient
      centred care (Patient Assessment of Chronic Illness Care). CONCLUSION: The MTBQ
      is a 10-item measure of treatment burden for patients with multimorbidity that
      has demonstrated good content validity, construct validity, reliability and
      responsiveness. It is a useful research tool for assessing the impact of
      interventions on treatment burden. TRIAL REGISTRATION NUMBER: ISRCTN06180958.

PMID- 29654012
TI  - Patient preferences for nutritional supplementation to improve fracture healing:
      a discrete choice experiment.
AB  - OBJECTIVE: Vitamin D is often prescribed as an adjuvant therapy to aid fracture
      healing due to its biological role in bone health. However, the optimal
      frequency, dosage and duration of vitamin D supplementation for non-osteoporotic
      fracture healing has not been established. The objective of this study was to
      determine patient preferences for fracture healing relative to hypothetical
      vitamin D supplementation dosing options. DESIGN: Discrete choice experiment.
      SETTING: Level 1 trauma centre in Baltimore, Maryland, USA. PARTICIPANTS: 199
      adult (18-60 years) patients with a fracture. PRIMARY OUTCOME MEASURES: Parameter
      estimates of utility for fracture healing relative to dosing regimens were
      analysed using hierarchical Bayesian modelling. RESULTS: A reduced risk of
      reoperation (34.3%) and reduced healing time (24.4%) were the attributes of
      greatest relative importance. The highest mean utility estimates were for a one
      time supplementation dose (beta=0.71, 95% CI 0.41 to 1.00) followed by a reduced
      risk of reoperation (beta=0.41 per absolute % reduction, 95% CI 0.0.36 to 0.46).
      Supplementation for 24 weeks in duration (beta=-0.83, 95% CI -1.00 to -0.67) and
      a daily supplement (beta=-0.29, 95% CI -0.47 to -0.11) had the lowest mean
      utilities. The 'no supplement' option had a large negative value suggesting
      supplementation was generally desirable in this sample population. Among other
      possible clinical scenarios, patients expected a 2% reduction in the absolute
      risk of reoperation or a 3.1-week reduction in healing time from the baseline to
      accept a treatment regimen requiring two separate doses of supplementation, two
      blood tests and a cost of $20 within 3 months of injury. CONCLUSIONS: Patients
      with orthopaedic trauma demonstrated strong willingness to take a vitamin D
      supplement that would decrease risk of reoperation and reduce healing time.
      Furthermore, these findings specify the required decrease in reoperation risk and
      reduction in healing time patients would expect to adhere to possible vitamin D
      dosing regimens.

PMID- 29654013
TI  - Comparison of three common nutritional screening tools with the new European
      Society for Clinical Nutrition and Metabolism (ESPEN) criteria for malnutrition
      among patients with geriatric gastrointestinal cancer: a prospective study in
      China.
AB  - OBJECTIVE: The aim of this study was to evaluate and compare three common
      nutritional screening tools with the new European Society for Clinical Nutrition
      and Metabolism (ESPEN) diagnostic criteria for malnutrition among elderly
      patients with gastrointestinal cancer. RESEARCH METHODSANDPROCEDURES: Nutritional
      screening tools, including the Nutritional Risk Screening 2002 (NRS 2002), the
      Malnutrition Universal Screening Tool (MUST) and the Short Form of Mini
      Nutritional Assessment (MNA-SF), were applied to 255 patients with
      gastrointestinal cancer. We compared the diagnostic values of these tools for
      malnutrition, using the new ESPEN diagnostic criteria for malnutrition as the
      'gold standards'. RESULTS: According to the new ESPEN diagnostic criteria for
      malnutrition, 20% of the patients were diagnosed as malnourished. With the use of
      NRS 2002, 52.2% of the patients were found to be at high risk of malnutrition;
      with the use of MUST, 37.6% of the patients were found to be at moderate/high
      risk of malnutrition; and according to MNA-SF, 47.8% of the patients were found
      to be at nutritional risk. MUST was best correlated with the ESPEN diagnostic
      criteria (K=0.530, p<0.001) compared with NRS 2002 (K=0.312, p<0.001) and MNA-SF
      (K=0.380, p<0.001). The receiver operating characteristic curve of MUST had the
      highest area under the curve (AUC) compared with NRS 2002 and MNA-SF.
      CONCLUSIONS: Among the tools, MUST was found to perform the best in
      identifyingmalnourished elderly patients with gastrointestinal cancer
      distinguished by the new ESPEN diagnostic criteria for malnutrition.
      Nevertheless, further studies are needed to verify our findings. TRIAL
      REGISTRATION NUMBER: ChiCTR-RRC-16009831; Pre-results.

PMID- 29654014
TI  - Regional South Australia Health (RESONATE) survey: study protocol.
AB  - INTRODUCTION: Access to quality healthcare services is considered a moral right.
      However, for people living in regional locations, timely access to the services
      that they need may not always be possible because of structural and attitudinal
      barriers. This suggests that people living in regional areas may have unmet
      healthcare needs. The aim of this research will be to examine the healthcare
      needs, expectations and experiences of regional South Australians. METHODS AND
      ANALYSIS: The Regional South Australia Health (RESONATE) survey is a cross
      sectional study of adult health consumers living in any private or non-private
      dwelling, in any regional, rural, remote or very remote area of South Australia
      and with an understanding of written English. Data will be collected using a 45
      item, multidimensional, self-administered instrument, designed to measure
      healthcare need, barriers to healthcare access and health service utilisation,
      attitudes, experiences and satisfaction. The instrument has demonstrated
      acceptable psychometric properties, including good content validity and internal
      reliability, good test-retest reliability and a high level of acceptability. The
      survey will be administered online and in hard-copy, with at least 1832 survey
      participants to be recruited over a 12-month period, using a comprehensive,
      multimodal recruitment campaign. ETHICS AND DISSEMINATION: The study has been
      reviewed and approved by the Human Research Ethics Committee of the University of
      South Australia. The results will be actively disseminated through peer-reviewed
      journals, conference presentations, social media, broadcast media, print media,
      the internet and various community/stakeholder engagement activities.

PMID- 29654015
TI  - Can microstructural MRI detect subclinical tissue injury in subjects with
      asymptomatic cervical spinal cord compression? A prospective cohort study.
AB  - OBJECTIVES: Degenerative cervical myelopathy (DCM) involves extrinsic spinal cord
      compression causing tissue injury and neurological dysfunction. Asymptomatic
      spinal cord compression (ASCC) is more common, but its significance is poorly
      defined. This study investigates if: (1) ASCC can be automatically diagnosed
      using spinal cord shape analysis; (2) multiparametric quantitative MRI can detect
      similar spinal cord tissue injury as previously observed in DCM. DESIGN:
      Prospective observational longitudinal cohort study. SETTING: Single centre,
      tertiary care and research institution. PARTICIPANTS: 40 neurologically intact
      subjects (19 female, 21 male) divided into groups with and without ASCC.
      INTERVENTIONS: None. OUTCOME MEASURES: Clinical assessments: modified Japanese
      Orthopaedic Association score and physical examination. 3T MRI assessments:
      automated morphometric analysis compared with consensus ratings of spinal cord
      compression, and measures of tissue injury: cross-sectional area, diffusion
      fractional anisotropy, magnetisation transfer ratio and T2*-weighted imaging
      white to grey matter signal intensity ratio (T2*WI WM/GM) extracted from rostral
      (C1-3), caudal (C6-7) and maximally compressed levels. RESULTS: ASCC was present
      in 20/40 subjects. Diagnosis with automated shape analysis showed area under the
      curve >97%. Five MRI metrics showed differences suggestive of tissue injury in
      ASCC compared with uncompressed subjects (p<0.05), while a composite of all 10
      measures (average of z scores) showed highly significant differences (p=0.002).
      At follow-up (median 21 months), two ASCC subjects developed DCM. CONCLUSIONS:
      ASCC appears to be common and can be accurately and objectively diagnosed with
      automated morphometric analysis. Quantitative MRI appears to detect subclinical
      tissue injury in ASCC prior to the onset of neurological symptoms and signs.
      These findings require further validation, but offer the intriguing possibility
      of presymptomatic diagnosis and treatment of DCM and other spinal pathologies.

PMID- 29654016
TI  - Association between physical activity and health-related quality of life in
      elderly individuals with pre-diabetes in rural Hunan Province, China: a cross
      sectional study.
AB  - OBJECTIVES: There are few data on the relationship between health-related quality
      of life (HRQoL) and physical activity among elderly individuals with pre
      diabetes. This study aimed to determine if differences existed in HRQoL between
      individuals with pre-diabetes who were physically active compared with those who
      were physically inactive in rural China. DESIGN, SETTING AND PARTICIPANTS: A
      cross-sectional survey was conducted among the elderly (?60 years) in rural
      communities in Yiyang City of China. Multistage cluster random sampling was
      carried out to select 42 areas, and interviews were conducted among 434 elderly
      individuals with pre-diabetes. Pre-diabetes was screened using an oral glucose
      tolerance test. MAIN OUTCOME MEASURES: The Medical Outcomes Study 36-Item Short
      Form Health Survey questionnaire was used to measure HRQoL. Physical activity was
      assessed using the International Physical Activity Questionnaire. Multivariate
      analysis of covariance (MANCOVA) was used to test for differences in HRQoL
      between the physically active group and the inactive group. RESULTS: A total of
      434 individuals with pre-diabetes were included in this study. The physical
      component summary (PCS) score of HRQoL was 42.1+/-10.2 and the mental component
      summary score was 46.4+/-8.9. A median total physical activity of 524 metabolic
      equivalent-min/week was reported. A significant MANCOVA model (Wilks'
      lambda=0.962, F(2,423)=8.44, P<0.001) indicated that elderly individuals with pre
      diabetes who were physically active reported higher PCS scores (Mdiff=5.2,
      P<0.001, effective size=0.47) compared with those physically inactive after
      adjusting for the following covariates: age, gender, marital status, education,
      smoking, chronic disease, body mass index and waist:hip ratio. CONCLUSIONS: The
      HRQoL of elderly individuals with pre-diabetes is poor in rural China. These
      findings demonstrated that elderly individuals with pre-diabetes who were
      physically active had higher PCS scores than those who were physically inactive.
      Furthermore, these results support the rationale for developing a physical
      activity intervention for HRQoL of individuals with pre-diabetes. TRIAL
      REGISTRATION NUMBER: ChiCTR-IOR-15007033; Results.

PMID- 29654017
TI  - Assessing prevalence of missed laboratory-confirmed sexually transmitted
      infections among women in Kingston, Jamaica: results from a secondary analysis of
      the Sino-Implant clinical trial.
AB  - OBJECTIVES: To assess potentially missed sexually transmitted infections (STIs),
      we compared clinically diagnosed STIs to laboratory-confirmed diagnoses of
      gonorrhoea (GC), chlamydia (CT) and trichomonas (Tvag). DESIGN: Secondary
      analysis of a randomised controlled trial. SETTING: We used data and specimens
      previously collected for the Sino-Implant Study in Kingston, Jamaica.
      PARTICIPANTS: The Sino-Implant Study randomised 414 women to receive a
      levonorgestrel implant at either baseline or 3 months post-enrolment to evaluate
      unprotected sex after implant initiation. This analysis used 254 available
      vaginal swab samples. OUTCOME MEASURES: Clinically diagnosed STIs were determined
      from medical records by assessing clinical impressions and prescriptions.
      Laboratory-confirmed STIs included GC, CT and Tvag tested by Aptima Combo 2 for
      CT/GC and Aptima Tvag assays (Hologic, San Diego, California, USA). Log-binomial
      regression models fit with generalised estimating equations were used to estimate
      associations of clinically diagnosed STIs with laboratory-confirmed diagnoses and
      demographic and behavioural characteristics. RESULTS: Overall, 195 (76.8%) women
      had laboratory-confirmed STI (CT, GC or Tvag) while only 65 (25.6%) women had
      clinically diagnosed cervicitis and/or vaginitis during the study period.
      Clinical diagnosis missed 79.7% of laboratory-confirmed STIs: 85% of GC
      (n=17/20), 78.8% of CT (n=141/179) and 80.0% of Tvag (n=180/225). Hormonal
      contraceptive use in the month prior to the study visit was significantly
      associated with clinical diagnosis at any time point (prevalence ratio (PR):
      1.65, 95% CI 1.07 to 2.54). As age increased, clinically missed infections
      significantly decreased (PR: 0.98 per year increase, 95% CI 0.97 to 1.00).
      CONCLUSIONS: The prevalence of laboratory-confirmed STIs was much higher than
      what was captured by clinical diagnosis. GC, CT and Tvag were not accurately
      detected without lab confirmation. Missed diagnoses decreased with older age.
      Increased laboratory capacity and refinement of the syndromic approach are needed
      to protect the health of sexually active Jamaican women. TRIAL REGISTRATION
      NUMBER: NCT01684358.

PMID- 29654018
TI  - Reducing early infant mortality in India: results of a prospective cohort of
      pregnant women using emergency medical services.
AB  - OBJECTIVES: To describe the demographic characteristics and clinical outcomes of
      neonates born within 7 days of public ambulance transport to hospitals across
      five states in India. DESIGN: Prospective observational study. SETTING: Five
      Indian states using a centralised emergency medical services (EMS) agency that
      transported 3.1 million pregnant women in 2014. PARTICIPANTS: Over 6 weeks in
      2014, this study followed a convenience sample of 1431 neonates born to women
      using a public-private ambulance service for a 'pregnancy-related' problem.
      Initial calls were deemed 'pregnancy related' if categorised by EMS dispatchers
      as 'pregnancy', 'childbirth', 'miscarriage' or 'labour pains'. Interfacility
      transfers, patients absent on ambulance arrival, refusal of care and neonates
      born to women beyond 7 days of using the service were excluded. MAIN OUTCOME
      MEASURES: death at 2, 7 and 42 days after delivery. RESULTS: Among 1684 women,
      1411 gave birth to 1431 newborns within 7 days of initial ambulance transport.
      Median maternal age at delivery was 23 years (IQR 21-25). Most mothers were from
      rural/tribal areas (92.5%) and lower social (79.9%) and economic status (69.9%).
      Follow-up rates at 2, 7 and 42 days were 99.8%, 99.3% and 94.1%, respectively.
      Cumulative mortality rates at 2, 7 and 42 days follow-up were 43, 53 and 62 per
      1000 births, respectively. The perinatal mortality rate (PMR) was 53 per 1000.
      Preterm birth (OR 2.89, 95% CI 1.67 to 5.00), twin deliveries (OR 2.80, 95% CI
      1.10 to 7.15) and caesarean section (OR 2.21, 95% CI 1.15 to 4.23) were the
      strongest predictors of mortality. CONCLUSIONS: The perinatal mortality rate
      associated with this cohort of patients with high-acuity conditions of pregnancy
      was nearly two times the most recent rate for India as a whole (28 per 1000
      births). EMS data have the potential to provide more robust estimates of PMR,
      reduce inequities in timely access to healthcare and increase facility-based care
      through service of marginalised populations.

PMID- 29654019
TI  - Effectiveness and cost-effectiveness of fining non-attendance at public
      hospitals: a randomised controlled trial from Danish outpatient clinics.
AB  - OBJECTIVES: Fines have been proposed as means for reducing non-attendance in
      healthcare. The empirical evidence of the effect of fines is however limited. The
      objective of this study is to investigate the effectiveness and cost
      effectiveness of fining non-attendance at outpatient clinics. DESIGN,
      PARTICIPANTS AND SETTING: 1:1 randomised controlled trial of appointments for an
      outpatient clinic, posted to Danish addresses, between 1 May 2015 and 30 November
      2015. Only first appointment for users was included. Healthcare professionals and
      investigators were masked. INTERVENTION: A fine of DKK250 (?34) was issued for
      non-attendance. Users were informed about the fine in case of non-attendance by
      the appointment letter, and were able to reschedule or cancel until the
      appointment. A central administration office administered the fine system. MAIN
      OUTCOME MEASURES: The main outcome measures were non-attendance of non-cancelled
      appointments, fine policy administration costs, net of productivity consequences
      and probability of fining non-attendance being cost-effective over no fining for
      a range of hypothetical values of reduced non-attendance. RESULTS: All of the
      6746 appointments included were analysed. Of the 3333 appointments randomised to
      the fine policy, 130 (5%) of non-cancelled appointments were unattended, and of
      the 3413 appointments randomised to no-fine policy, 131 (5%) were unattended. The
      cost per appointment of non-attendance was estimated at DKK 56 (SE 5) in the fine
      group and DKK47 (SE 4) in the no-fine group, leading to a non-statistically
      significant difference of DKK10 (95% CI -9 to 22) per appointment attributable to
      the fine policy. The probability of cost-effectiveness remained around 50%,
      irrespective of increased values of reduced non-attendance or various alternative
      assumptions used for sensitivity analyses. CONCLUSIONS: At a baseline level of
      around 5%, fining non-attendance does not seem to further reduce non-attendance.
      Future studies should focus on other means for reduction of non-attendance such
      as nudging or negative reinforcement. TRIAL REGISTRATION NUMBER: ISRCTN61925912.

PMID- 29654020
TI  - Gender inequalities in the association between area deprivation and perceived
      social support: a cross-sectional multilevel analysis at the municipality level
      in Germany.
AB  - OBJECTIVES: To investigate the association between area deprivation at
      municipality level with low perceived social support, independent of individual
      socioeconomic position and demographic characteristics. To assess whether there
      are gender inequalities in this association. DESIGN: Cross-sectional multilevel
      analysis of survey data. SETTING: Germany. PARTICIPANTS: 3350 men and 3665 women
      living in 167 municipalities throughout Germany participating in the 'German
      Health Interview and Examination Survey for Adults' (DEGS1 2008-2011) as part of
      the national health monitoring. OUTCOME: Perceived social support as measured by
      Oslo-3 Social Support Scale. RESULTS: Prevalence of low perceived social support
      was 11.4% in men and 11.1% in women. Low social support was associated in men and
      women with sociodemographic characteristics that indicate more disadvantaged
      living situations. Taking these individual-level characteristics into account,
      municipal-level deprivation was independently associated with low perceived
      social support in men (OR for the most deprived quintile: 1.80 (95% CI 1.14 to
      2.84)), but not in women (OR 1.22 (95% CI 0.78 to 1.90)). CONCLUSION: The results
      of our multilevel analysis suggest that there are gender inequalities in the
      association of municipal-level deprivation with the prevalence of low perceived
      social support in Germany independent of individual socioeconomic position.
      Community health interventions aiming at promotion of social support among
      residents might profit from a further understanding of the observed gender
      differences.

PMID- 29654021
TI  - Awareness of diabetic retinopathy and its association with attendance for
      systematic screening at the public primary care setting: a cross-sectional study
      in Hong Kong.
AB  - OBJECTIVE: To assess the association between awareness of diabetic retinopathy
      (DR) and actual attendance for DR screening. DESIGN: Cross-sectional study.
      SETTING: Two public general outpatient clinics. PARTICIPANTS: The subjects were
      people with diabetes mellitus (DM) who participated in a randomised controlled
      trial, set up in 2008, to test the impact of a copayment on attendance for DR
      screening. PRIMARY AND SECONDARY OUTCOME MEASURES: The subjects' awareness of DR
      was evaluated using a structured questionnaire conducted via a telephone
      interview. The attendance for screening was from the actual attendance data.
      Association between awareness and attendance for screening was determined using
      multivariate logistic regression model and was reported as ORs. RESULTS: A total
      of 2593 participants completed the questionnaire. A total of 42.9% (1113/2593)
      said they would worry if they had any vision loss and 79.6% (2063/2593) knew that
      DM could cause blindness. Only 17.5% (453/2593) knew that treatment was available
      for DR and 11.5% (297/2593) knew that early DR could be asymptomatic. The
      importance of having a regular eye examination was acknowledged by 75.7%
      (1964/2593), but 34% (881/2593) did not know how frequently their eyes should be
      examined. Worry about vision loss (OR=1.72, P<0.001), awareness of the importance
      of regular eye examination (OR=1.83, P=0.002) and awareness of the frequency of
      eye examinations ('every year' (OR=2.64, P<0.001) or 'every 6 months' (OR=3.27,
      P<0.001)) were the most significant factors associated with attendance.
      CONCLUSIONS: Deficits in knowledge of DR and screening were found among subjects
      with DM, and three awareness factors were associated with attendance for
      screening. These factors could be targeted for future interventions.

PMID- 29654022
TI  - Gender disparities in high-quality dermatology research: a descriptive
      bibliometric study on scientific authorships.
AB  - OBJECTIVE: The present study aims to elucidate the state of gender equality in
      high-quality dermatological research by analysing the representation of female
      authorships from January 2008 to May 2017. DESIGN: Retrospective, descriptive
      study. SETTING: 113 189 male and female authorships from 23 373 research articles
      published in 23 dermatological Q1 journals were analysed with the aid of the
      Gendermetrics Platform. RESULTS: 43.0% of all authorships and 50.2% of the
      firstauthorships, 43.7% of the coauthorships and 33.1% of the last authorships
      are held by women. The corresponding female-to-male ORs are 1.41 (95% CI 1.37 to
      1.45) for first authorships, 1.07 (95% CI 1.04 to 1.10) for coauthorships and
      0.60 (95% CI 0.58 to 0.62) for last authorships. The annual growth rates are
      1.74% overall and 1.45% for first authorships, 1.53% for coauthorships and 2.97%
      for last authorships. Women are slightly under-represented at prestigious
      authorships compared with men (Prestige Index=-0.11). The under-representation
      remains stable in highly competitive articles attracting the highest citation
      rates, namely, articles with many authors and articles that were published in
      highest-impact journals. Multiauthor articles with male key authors are only
      slightly more frequently cited than those with female key authors. Women publish
      slightly fewer papers compared with men (47.2% women hold 43.0% of the
      authorships). At the level of individual journals, there is a high degree of
      uniformity in gender-specific authorship odds. By contrast, distinct differences
      at country level were revealed. The prognosis for the next decades forecasts a
      consecutive harmonisation of authorship odds between the two genders.
      CONCLUSIONS: In high-quality dermatological research, the integration of female
      scholars is advanced as compared with other medical disciplines. A gender gap
      consists mainly in the form of a career dichotomy, with many female early career
      researchers and few women in academic leadership positions. However, this gender
      gap has been narrowed in the last decade and will likely be further reduced in
      the future.

PMID- 29654023
TI  - OPTIMAL and ENSURE trials-based combined cost-effectiveness analysis of erlotinib
      versus chemotherapy for the first-line treatment of Asian patients with non
      squamous non-small-cell lung cancer.
AB  - OBJECTIVES: Erlotinib, the first generation of epidermoid growth factor receptor
      tyrosine kinase inhibitor (EGFR-TKI), has been recommended as an essential
      treatment in patients with non-small-cell lung cancer (NSCLC) with EGFR mutation.
      Although it has improved progression-free survival (PFS), overall survival (OS)
      was limited and erlotinib can be expensive. This cost-effectiveness analysis
      compares erlotinib monotherapy with gemcitabine-included doublet chemotherapy.
      SETTING: First-line treatment of Asian patients with NSCLC with EGFR mutation.
      METHODS: A Markov model was created based on the results of the ENSURE
      (NCT01342965) and OPTIMAL (CTONG-0802) trials which evaluated erlotinib and
      chemotherapy. The model simulates cancer progression and all causes of death. All
      medical costs were calculated from the perspective of the Chinese healthcare
      system. MAIN OUTCOME MEASURES: The primary outcomes are costs, quality-adjusted
      life years (QALYs) and incremental cost-effectiveness ratios (ICERs). RESULTS:
      The combined PFS was 11.81 months and 5.1 months for erlotinib and chemotherapy,
      respectively, while the OS was reversed at 24.68 months for erlotinib and 26.16
      months for chemotherapy. The chemotherapy arm gained 0.13 QALYs compared with
      erlotinib monotherapy (1.17 QALYs vs 1.04 QALYs), while erlotinib had lower costs
      ($55 230 vs $77 669), resulting in an ICER of $174 808 per QALY for the
      chemotherapy arm, which exceeds three times the Chinese GDP per capita. The most
      influential factors were the health utility of PFS, the cost of erlotinib and the
      health utility of progressed disease. CONCLUSION: Erlotinib monotherapy may be
      acceptable as a cost-effective first-line treatment for NSCLC compared with
      gemcitabine-based chemotherapy. The results were robust to changes in
      assumptions. TRIAL REGISTRATION NUMBER: NCT01342965 and CTONG-0802.

PMID- 29654024
TI  - Effect of maternal age on facility-based delivery: analysis of first-order births
      in 34 countries of sub-Saharan Africa using demographic and health survey data.
AB  - OBJECTIVES: Increasing access to skilled birth attendance, usually via childbirth
      in health facilities, is a key intervention to reduce maternal and perinatal
      mortality and morbidity. Yet, in some countries of sub-Saharan Africa, the uptake
      is <50%. Age and parity are determinants of facility-based delivery, but are
      strongly correlated in high fertility settings. This analysis assessed the
      independent effect of age on facility-based delivery by restricting to first
      order births. It was hypothesised that older first-time mothers in this setting
      might have lower uptake of facility-based deliveries than women in the most
      common age groups for first birth. SETTING: The most recent Demographic and
      Health Surveys from 34 sub-Saharan African countries were used to assess women's
      delivery locations. PARTICIPANTS: 72 772 women having their first birth in the 5
      years preceding the surveys were included in the analysis. PRIMARY AND SECONDARY
      OUTCOME MEASURES: Proportions and 95% CIs of facility-based deliveries were
      estimated overall and by country. Multivariable logistic regression was used to
      calculate the odds of facility-based delivery for different maternal age groups
      (15-19, 20-24 and >=25 years) for a pooled sample of all countries. RESULTS:
      59.9% of women had a facility-based delivery for their first birth (95% CI 58.6
      to 61.2), ranging from 19.4% in Chad to 96.6% in Rwanda. Compared with women aged
      15-19 years, the adjusted odds of having a facility-based delivery for those aged
      20-24 was 1.4 (95% CI 1.3 to 1.5, p<0.001) and for those aged >=25, 1.9 (95% CI
      1.6 to 2.2, p<0.001). CONCLUSIONS: Older age at first birth was independently
      associated with significantly higher odds of facility-based delivery. This went
      against the hypothesis. Further mixed-method research is needed to explore how
      increased age improves uptake of facility-based delivery. Promoting facility
      based delivery, while ensuring quality of care, should be prioritised to improve
      birth outcomes in sub-Saharan Africa.

PMID- 29654025
TI  - Cancer-related information needs and treatment decision-making experiences of
      people with dementia in England: a multiple perspective qualitative study.
AB  - OBJECTIVES: Little is known about the cancer experience and support needs of
      people with dementia. In particular, no evidence currently exists to demonstrate
      the likely complex decision-making processes for this patient group and the
      oncology healthcare professionals (HCP) involved in their care. The aim of this
      study was to explore the cancer-related information needs and decision-making
      experiences of patients with cancer and comorbid dementia, their informal
      caregivers and oncology HCPs. DESIGN: Cross-sectional qualitative study.
      Semistructured interviews were conducted face to face with participants.
      Interviews were audio recorded and transcribed prior to thematic analysis.
      SETTING: Patients with a diagnosis of cancer and dementia, their informal
      caregivers and oncology HCPs involved in their care, all recruited from a
      regional treatment cancer centre. PARTICIPANTS: Purposeful sample of 10 patients
      with a diagnosis of cancer-dementia, informal caregivers (n=9) and oncology HCPs
      (n=12). RESULTS: Four themes were identified: (1) leading to the initial
      consultation-HCPs require more detailed information on the functional impact of
      dementia and how it may influence cancer treatment options prior to meeting the
      patient; (2) communicating clinically relevant information-informal caregivers
      are relied on to provide patient information, advocate for the patient and
      support decision-making; (3) adjustments to cancer care-patients with dementia
      get through treatment with the help of their family and (4) following completion
      of cancer treatment-there are continuing information needs. Oncology HCPs
      discussed their need to consult specialists in dementia care to support treatment
      decision-making. CONCLUSIONS: Although patients with cancer-dementia are involved
      in their treatment decision-making, informal caregivers are generally crucial in
      supporting this process. Individual patient needs and circumstances related to
      their cancer must be considered in the context of dementia prognosis highlighting
      complexities of decision-making in this population. Oncology teams should strive
      to involve healthcare staff with dementia expertise as early as possible in the
      cancer pathway.

PMID- 29654028
TI  - Digital Support Platform: a qualitative research study investigating the
      feasibility of an internet-based, postdiagnostic support platform for families
      living with dementia.
AB  - OBJECTIVES: To establish the feasibility of the Digital Support Platform (DSP),
      an internet-based, postdiagnostic tool designed for families living with a
      diagnosis of dementia. DESIGN: Qualitative methods using normalisation process
      theory as an analysis framework for semistructured interview transcriptions.
      SETTING: A community care setting in the South-East Scotland. PARTICIPANTS: We
      interviewed 10 dyads of people with Alzheimer's, vascular or mixed dementia
      (PWD), and their family carers, who had been given and had used the DSP for at
      least 2 months. RESULTS: Our analysis revealed that the DSP was predominantly
      understood and used by the carers rather than PWD, and was used alongside tools
      and methods they already used to care for their relative. The DSP was interpreted
      as a tool that may be of benefit to those experiencing later stages of dementia
      or with physical care needs. Carers stated that the DSP may be of benefit in the
      future, reflecting a disinclination to prepare for or anticipate for future
      needs, rather than focus on those needs present at the time of distribution. PWD
      spoke positively about an interest in learning to use technology more effectively
      and enjoyed having their own tablet devices. CONCLUSIONS: The DSP was not wholly
      appropriate for families living with dementia in its early stages. The views of
      carers confirmed that postdiagnostic support was valued, but emphasised the
      importance of tailoring this support to the exact needs and current arrangements
      of families. There may be a benefit to introducing, encouraging, providing and
      teaching internet-enabled technology to those PWD who do not currently have
      access. Training should be provided when introducing new technology to PWD.

PMID- 29654026
TI  - Cost of hospitalised patients due to complicated urinary tract infections: a
      retrospective observational study in countries with high prevalence of multidrug
      resistant Gram-negative bacteria: the COMBACTE-MAGNET, RESCUING study.
AB  - OBJECTIVE: Complicated urinary tract infections (cUTIs) impose a high burden on
      healthcare systems and are a frequent cause of hospitalisation. The aims of this
      paper are to estimate the cost per episode of patients hospitalised due to cUTI
      and to explore the factors associated with cUTI-related healthcare costs in eight
      countries with high prevalence of multidrug resistance (MDR). DESIGN: This is a
      multinational observational, retrospective study. The mean cost per episode was
      computed by multiplying the volume of healthcare use for each patient by the unit
      cost of each item of care and summing across all components. Costs were measured
      from the hospital perspective. Patient-level regression analyses were used to
      identify the factors explaining variation in cUTI-related costs. SETTING: The
      study was conducted in 20 hospitals in eight countries with high prevalence of
      multidrug resistant Gram-negative bacteria (Bulgaria, Greece, Hungary, Israel,
      Italy, Romania, Spain and Turkey). PARTICIPANTS: Data were obtained from 644
      episodes of patients hospitalised due to cUTI. RESULTS: The mean cost per case
      was ?5700, with considerable variation between countries (largest value ?7740 in
      Turkey; lowest value ?4028 in Israel), mainly due to differences in length of
      hospital stay. Factors associated with higher costs per patient were: type of
      admission, infection source, infection severity, the Charlson comorbidity index
      and presence of MDR. CONCLUSIONS: The mean cost per hospitalised case of cUTI was
      substantial and varied significantly between countries. A better knowledge of the
      reasons for variations in length of stays could facilitate a better standardised
      quality of care for patients with cUTI and allow a more efficient allocation of
      healthcare resources. Urgent admissions, infections due to an indwelling urinary
      catheterisation, resulting in septic shock or severe sepsis, in patients with
      comorbidities and presenting MDR were related to a higher cost.

PMID- 29654027
TI  - Comparison of intravenous versus combined oral and intravenous antimicrobial
      prophylaxis (COMBINE) for the prevention of surgical site infection in elective
      colorectal surgery: study protocol for a multicentre, double-blind, randomised
      controlled clinical trial.
AB  - INTRODUCTION: Surgical site infections (SSIs) account for 30% of all healthcare
      associated infections, with reported rates ranging from 8% and 30% after
      colorectal surgery and are associated with increased morbidity and mortality
      rates, length of hospital stay and costs in healthcare. Administration of
      systemic antimicrobial prophylaxis before surgery is recommended to reduce the
      risk of SSI, but the optimal regimen remains unclear. We aim to evaluate whether
      a combined oral and intravenous antimicrobial prophylaxis could be more effective
      to reduce the incidence of SSI after colorectal surgery, as compared with the
      standard practice of intravenous antimicrobial prophylaxis alone. METHODS AND
      ANALYSIS: Comparison of intravenous versus combined oral and intravenous
      antimicrobial prophylaxis (COMBINE) trial is a randomised, placebo-controlled,
      parallel, double-blind, multicentre study of 960 patients undergoing elective
      colorectal surgery. Patients will be randomly allocated in a 1:1 ratio to receive
      either combined oral and intravenous antimicrobial prophylaxis or intravenous
      antibiotic prophylaxis alone, stratified by centre, the surgical procedure
      (laparoscopic or open surgery) and according to the surgical skin antisepsis
      (chlorexidine-alcohol or povidione-iodine alcoholic solution). The primary
      endpoint is the rate of SSI by day 30 following surgery, with SSI defined by the
      criteria developed by the Centers for Disease Control and Prevention. Data will
      be analysed on the intention-to-treat principle and a per-protocol basis. ETHICS
      AND DISSEMINATION: COMBINE trial has been approved by an independent ethics
      committee for all study centres. Participant recruitment began in May 2016.
      Results will be published in international peer-reviewed medical journals. TRIAL
      REGISTRATION NUMBER: EudraCT 2015-002559-84; NCT02618720.

PMID- 29654029
TI  - Dementia in UK South Asians: a scoping review of the literature.
AB  - OBJECTIVE: Over 850 000 people live with dementia in the UK. A proportion of
      these people are South Asians, who make up over 5% of the total UK population.
      Little is known about the prevalence, experience and treatment of dementia in the
      UK South Asian population. The aim of this scoping review is to identify dementia
      studies conducted in the UK South Asian population to highlight gaps in the
      literature which need to be addressed in future research. METHOD: Databases were
      systematically searched using a comprehensive search strategy to identify
      studies. A methodological framework for conducting scoping reviews was followed.
      An extraction form was developed to chart data and collate study characteristics
      and findings. Studies were then grouped into six categories: prevalence and
      characteristics; diagnosis validation and screening; knowledge, understanding and
      attitudes; help-seeking; experience of dementia; service organisation and
      delivery. RESULTS: A total of 6483 studies were identified, 27 studies were
      eligible for inclusion in the scoping review. We found that studies of
      prevalence, diagnosis and service organisation and delivery in UK South Asians
      are limited. We did not find any clinical trials of culturally appropriate
      interventions for South Asians with dementia in the UK. The existing evidence
      comes from small-scale service evaluations and case studies. CONCLUSIONS: This is
      the first scoping review of the literature to identify priority areas for
      research to improve care for UK South Asians with dementia. Future research
      should first focus on developing and validating culturally appropriate diagnostic
      tools for the UK South Asians and then conducting high-quality epidemiological
      studies in order to accurately identify the prevalence of dementia in this group.
      The cultural adaptation of interventions for dementia and testing in randomised
      controlled trials is also vital to ensure that there are appropriate treatments
      available for the UK South Asians to access.

PMID- 29654030
TI  - A protocol for a Canadian prospective observational study of decision-making on
      active surveillance or surgery for low-risk papillary thyroid cancer.
AB  - INTRODUCTION: Low-risk papillary thyroid cancer (PTC) is increasingly being
      diagnosed throughout the world; yet the mortality risk is low compared with other
      malignancies. Traditional management includes thyroid surgery, sometimes followed
      by radioactive iodine and thyroid hormone treatment. Active surveillance (AS) has
      been proposed as a means to reduce overtreatment of PTC. AS involves close
      disease follow-up, with the intention to intervene if the disease progresses, or
      on patient request. METHODS AND ANALYSIS: This is a multiphase prospective
      observational study. In the first phase of this study, consenting eligible adults
      with low-risk PTC, that is, <2 cm in maximal diameter, confined to the thyroid
      and not immediately adjacent to critical structures in the neck, are provided
      verbal and written information about PTC disease prognosis following surgery or
      AS. Questionnaires are administered at baseline and after the disease management
      decision on AS or surgery is finalised. Patients may choose either option
      (surgery or AS), and the primary outcome is the frequency with which either
      disease management option is chosen. Secondary outcomes include: rationale for
      the decision, role of the patient in decision-making and decision satisfaction.
      In the second phase of the study, consenting eligible adult patients who
      completed the first study phase may enrol in respective AS or surgery group
      follow-up studies. The following outcomes are examined 1 year after enrolment in
      the follow-up phase: decision regret about disease management choice (primary
      outcome), psychological distress, disease-specific quality of life, fear of
      disease progression, body image satisfaction, disease progression, crossover to
      surgery in the AS group, new chronic thyroid hormone use and healthcare resource
      utilisation. ETHICS AND DISSEMINATION: The University Health Network Research
      Ethics Board approved this study (ID 15-8942). The results will be published in
      an open access journal. TRIAL REGISTRATION NUMBER: NCT03271892; Pre-results.

PMID- 29654031
TI  - Hip fracture incidence and mortality in chronic kidney disease: the GLOMMS-II
      record linkage cohort study.
AB  - BACKGROUND: Individuals on renal replacement therapy (RRT) have increased
      fracture risk, but risk in less advanced chronic kidney disease (CKD) is unclear.
      OBJECTIVE: To investigate CKD associations with hip fracture incidence and
      mortality. DESIGN: Record linkage cohort study Grampian Laboratory Outcomes
      Mortality and Morbidity Study II. SETTING: Single health region in Scotland.
      PARTICIPANTS: All individuals (>=15 years) with sustained CKD stages 3-5 and
      those on RRT, and a 20% random sample of those with normal renal function, in the
      resident population in 2003. OUTCOME MEASURES: Outcomes were (1) incident hip
      fracture measured with (A) admissions or (B) deaths, with at least 5.5 years
      follow-up and (2) post-hip fracture mortality. Unadjusted and adjusted, incident
      rate ratios (IRRs) and mortality rate ratios were calculated using Poisson
      regression. RESULTS: Of 39 630 individuals identified in 2003 (41% males, mean
      age 63.3 years), 19 537 had CKD stages 3-5, 345 were on RRT and 19 748 had normal
      estimated glomerular filtration rate (eGFR). Hip fracture incidence, measured by
      admissions, was increased in CKD stages 3-5 (compared with normal eGFR), both
      overall (adjusted IRR 1.49 (95% CI 1.24 to 1.79)) and for individual CKD stages
      3a, 3b and 4. Hip fracture incidence, measured using deaths, was increased in
      those with CKD stages 3b and 4. Post-hip fracture mortality was only increased in
      CKD stage 4. There was only a small number of individuals and events for CKD
      stage 5, resulting in insufficient statistical power. CONCLUSION: Hip fracture
      incidence was higher in CKD stages 3-5 compared with normal eGFR. Post-hip
      fracture mortality was only increased in CKD stage 4. Reducing hip fracture
      incidence in CKD through regular fall and fracture risk review should reduce
      overall deaths after hip fracture in the population.

PMID- 29654032
TI  - Scaling the Peaks Research Protocol: understanding the barriers and drivers to
      providing and using dementia-friendly community services in rural areas-a mixed
      methods study.
AB  - INTRODUCTION: Scaling the Peaks is a cross-disciplinary research study that draws
      on medical ethnography, human geography and Geospatial Information Science (GIS)
      to address the issues surrounding the design and delivery of dementia-friendly
      services in rural communities. The research question seeks to understand the
      barriers and drivers to the development of relevant, robust, reliable and
      accessible services that make a difference among older rural families affected by
      dementia. METHODS AND ANALYSIS: This mixed methods study recruits both families
      affected by dementia who reside within the Peak District National Park,
      Derbyshire, and their service providers. The study explores the expectations and
      experiences of rural dementia by adopting a three-part approach 1 : longitudinal
      ethnographic enquiry with up to 32 families affected by dementia (aged 70 years
      plus) who identify themselves as rural residents 2 ; ethnographic semistructured
      interviews and systematic observations of a range of statutory, third sector,
      private and local community initiatives that seek to support older people living
      with dementia 3 ; and geospatial visual mapping of the qualitative and
      quantitative data. The ethnographic data will be used to explore the ideas of
      belonging in a community, perceptions of place and identity to determine the
      factors that influence everyday decisions about living well with dementia and,
      for the providers, working in a rural community. The geospatial component of the
      study seeks to incorporate quantitative and qualitative data, such as types,
      locations and allocation of services to produce an interactive web-based map for
      local communities to determine the future design and delivery of services when
      considering dementia-friendly services. ETHICS AND DISSEMINATION: The study is
      approved by the Leeds and Humberside Health Research Authority 16/YH/0163. The
      study is also approved by other participating organisations as required by their
      own governance procedures. The study includes people with dementia and as such
      adheres to the ethical considerations when including people with dementia. A
      publicly available interactive visual map of the findings will be produced in
      relation to current services related to location and, by default, identify gaps
      in provision. Formal reports and dissemination activities will be undertaken in
      collaboration with the study advisory group members. STUDY PROGRESS: The
      recruitment began in September 2016. The data analysis commenced June 2017, using
      59 provider interviews and 27 family participants. Data collection will be
      completed June 2018. NOTE ON TERMINOLOGY: Please note that the term 'families
      affected by dementia' is the preferred term of usage by the family members of the
      Scaling the Peaks Study Advisory Group. The group wish to emphasise that they
      consider this term to be more representative of their lives than the term living
      with dementia. TRIAL REGISTRATION NUMBER: NIHR IRAS 188103; Pre-results.

PMID- 29654033
TI  - A UK clinical audit addressing the quality of prescribing of sodium valproate for
      bipolar disorder in women of childbearing age.
AB  - OBJECTIVES: To review prescribing practice concerning valproate, an established
      human teratogen, for the management of bipolar disorder in women of childbearing
      age. DESIGN: The Prescribing Observatory for Mental Health conducted a baseline
      clinical audit in the UK, as part of a quality improvement programme.
      PARTICIPANTS: Six hundred and forty-eight clinical teams from 55 mental health
      Trusts submitted retrospective treatment data relating to patients with a
      diagnosis of bipolar disorder. RESULTS: Of the audit sample of 6705 patients,
      3854 were 50 years of age or younger. Valproate was prescribed for 24% of women
      and 43% men in this age group, and the mean dose of valproate was lower in women
      (1196 mg) than in men (1391 mg). For only half of such women was there documented
      evidence that information had been provided on the risks for the unborn child and
      the need for adequate contraception. Valproate was more often used in men to
      treat mania and aggression, while the most common treatment targets in women were
      hypomania and relapse prevention. CONCLUSIONS: Despite explicit recommendations
      in national treatment guidelines and published safety alerts and warnings
      regarding the use of valproate in women of childbearing age, current prescribing
      of this medication to such women in the context of the treatment of bipolar
      disorder falls short of best practice, particularly with regard to provision of
      information regarding the risks associated with exposure to valproate during
      pregnancy. While women younger than 50 years of age were less likely to be
      prescribed valproate than men in the same age group, and at a lower dosage, it is
      unclear to what extent this reflects clinicians' concerns about teratogenicity or
      is driven by perceptions of the indication for valproate, and the dosage
      required, for the treatment of different phases of the disorder in men and women.

PMID- 29654034
TI  - Enablers and barriers to improving worksite canteen nutrition in Pudong, China: a
      mixed-methods formative research study.
AB  - OBJECTIVE: To identify individual-level and organisation-level enablers and
      barriers to the provision and consumption of healthier foods at worksite canteens
      in China and to develop a theoretical framework and evidence-based, specific,
      practical intervention strategies. DESIGN: Mixed-methods formative research, with
      in-depth interviews, focus group discussions and quantitative questionnaires.
      SETTING: Two community health centres (CHCs) in Pudong, Shanghai, China.
      PARTICIPANTS: In-depth interviews with three CHC administrators and three canteen
      managers and staff. Six focus groups with a total of 19 male and 36 female
      employees, aged 25-67 years. RESULTS: Three subthemes were identified as
      important for influencing individual food choice: the cultural perception of
      'eating well', the need to balance taste preferences and nutrition, and the
      emphasis on food safety in healthfulness. At the organisation level, two related
      subthemes emerged: the balance of canteen budget and food safety with the variety
      and quality of offerings, and the interplay between key stakeholders. Key
      barriers included cost, poor communication between employees and management,
      individuals' emphasis on taste over healthfulness, variation in individual
      preferences and discordance between perceived and actual weight status,
      particularly among men. Key enablers included strong, positive food culture in
      China and trust in canteen food. An ecological framework to describe determinants
      of worksite food environment in Shanghai was developed and intervention
      strategies were mapped onto this framework. CONCLUSIONS: A balancing act occurs
      at multiple levels and ultimately determines the worksite food environment and
      employee food choice at CHCs in Shanghai of China. There is a need to implement
      these findings and evaluate their impact on diet and health.

PMID- 29654035
TI  - Associations between blood cadmium levels and cognitive function in a cross
      sectional study of US adults aged 60 years or older.
AB  - OBJECTIVES: The relationship between cadmium exposure and cognition has been well
      studied in children. However, the association between environmental cadmium
      exposure and cognitive function has not been researched extensively in older
      adults. Our goal was to evaluate the association between cognitive function and
      blood cadmium levels in US adults aged 60 years or older. DESIGN: A cross
      sectional study. SETTING: The US National Health and Nutrition Examination Survey
      (NHANES). PARTICIPANTS: A total of 2068 adults aged 60 years or older who
      completed four cognitive assessment tests and blood cadmium detection in two
      waves of NHANES (2011-2014). MAIN OUTCOME MEASURES: Cognitive assessment was
      conducted by household interview or at a Mobile Examination Center (MEC) using
      the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word List
      Learning Test, the CERAD Word List Recall Test, the Animal Fluency Test and the
      Digit Symbol Substitution Test (DSST). We created a composite cognitive z-score
      to represent global cognitive function. RESULTS: The median blood cadmium
      concentration in the study participants was 0.35 ug/L, and the IQR was 0.24-0.56
      ug/L. In linear regression analyses, adjusting for demographics, behaviour and
      medical history, blood cadmium as a continuous variable was inversely associated
      with the composite z-score (MUg/L, beta=-0.11, 95% CI -0.20 to -0.03). Similarly,
      there was a significant association between quartiles of blood cadmium and
      composite z-score, with somewhat lower scores in the upper quartile of exposure
      (blood cadmium >=0.63 ug/L) compared with those in the lower quartile of exposure
      (blood cadmium <0.25 ug/L) (MUg/L, beta=-0.14, 95% CI -0.25 to -0.03), and there
      was a trend by quartiles of blood cadmium (P<0.0001). CONCLUSIONS: Our findings
      suggest that increased blood cadmium is associated with worse cognitive function
      in adults aged 60 years or older in the USA.

PMID- 29654036
TI  - Improving antibiotic prescribing by general practitioners: a protocol for a
      systematic review of interventions involving pharmacists.
AB  - INTRODUCTION: Effective antibiotic options in general practice for patients with
      infections are declining significantly due to antibiotic over-prescribing and
      emerging antibiotic resistance. To better improve antibiotic prescribing by
      general practitioner (GP), pharmacist-GP collaborations have been promoted under
      antibiotic stewardship programmes. However, there is insufficient information
      about whether and how pharmacists help GPs to more appropriately prescribe
      antibiotics. This systematic review aims to determine whether pharmacist-led or
      pharmacist-involved interventions are effective at improving antibiotic
      prescribing by GPs. METHODS AND ANALYSIS: A systematic review of English language
      randomised controlled trials (RCTs), cluster RCTs, controlled before-and-after
      studies and interrupted time series studies cited in MEDLINE, EMBASE, EMCARE,
      CINAHL Plus, PubMed, PsycINFO, Cochrane Central Register of Controlled Trials and
      Web of Science databases will be conducted. Studies will be included if a
      pharmacist is involved as the intervention provider and GPs are the intervention
      recipients in general practice setting. Data extraction and management will be
      conducted using Effective Practice and Organisation of Care data abstraction
      tools and a template for intervention description and replication. The Cochrane
      and ROBINS-I risk of bias assessment tools will be used to assess the
      methodological quality of studies. Primary outcome measures include changes
      (overall, broad spectrum and guidelines concordance) of GP-prescribed
      antibiotics. Secondary outcomes include quality of antibiotic prescribing,
      delayed antibiotic use, acceptability and feasibility of interventions. Meta
      analysis for combined effect and forest plots, chi2 test and I2 statistics for
      detailed heterogeneity and sensitivity analysis will be performed if data permit.
      Grading of Recommendations Assessment, Development and Evaluation and Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidance will
      be used to report findings. ETHICS AND DISSEMINATION: No ethics approval is
      required as no primary, personal or confidential data are being collected in this
      study. The findings will be disseminated to national and international scientific
      sessions and published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER:
      CRD42017078478.

PMID- 29654037
TI  - Current practice of usual clinic blood pressure measurement in people with and
      without diabetes: a survey and prospective 'mystery shopper' study in UK primary
      care.
AB  - OBJECTIVES: Hypertension trials and epidemiological studies use multiple clinic
      blood pressure (BP) measurements at each visit. Repeat measurement is also
      recommended in international guidance; however, little is known about how BP is
      measured routinely. This is important for individual patient management and
      because routinely recorded readings form part of research databases. We aimed to
      determine the current practice of BP measurement during routine general practice
      appointments. DESIGN: (1) An online cross-sectional survey and (2) a prospective
      'mystery shopper' study where patients agreed to report how BP was measured
      during their next appointment. SETTING: Primary care. PARTICIPANTS: Patient
      charity/involvement group members completing an online survey between July 2015
      and January 2016. 334 participants completed the prospective study (51.5% male,
      mean age=59.3 years) of which 279 (83.5%) had diabetes. PRIMARY OUTCOME:
      Proportion of patients having BP measured according to guidelines. RESULTS: 217
      participants with (183) and without diabetes (34) had their BP measured at their
      last appointment. BP was measured in line with UK guidance in 63.7% and 60.0% of
      participants with and without diabetes, respectively. Initial pressures were
      significantly higher in those who had their BP measured more than once compared
      with only once (p=0.016/0.089 systolic and p<0.001/p=0.022 diastolic, in patients
      with/without diabetes, respectively). CONCLUSIONS: Current practice of routine BP
      measurement in UK primary care is often concordant with guidelines for repeat
      measurement. Further studies are required to confirm findings in broader
      populations, to confirm when a third repeat reading is obtained routinely and to
      assess adherence to other aspects of BP measurement guidance.

PMID- 29654038
TI  - Efficacy of nurse-led and general practitioner-led comprehensive geriatric
      assessment in primary care: protocol of a pragmatic three-arm cluster randomised
      controlled trial (CEpiA study).
AB  - INTRODUCTION: Older patients raise therapeutic challenges, because they
      constitute a heterogeneous population with multimorbidity. To appraise this
      complexity, geriatricians have developed a multidimensional comprehensive
      geriatric assessment (CGA), which may be difficult to apply in primary care
      settings. Our primary objective was to compare the effect on morbimortality of
      usual care compared with two complex interventions combining educational seminars
      about CGA: a dedicated geriatric hotline for general practitioners (GPs) and CGA
      by trained nurses or GPs. METHODS AND ANALYSIS: The Clinical Epidemiology and
      Ageing study is an open-label, pragmatic, multicentre, three-arm, cluster
      randomised controlled trial comparing two intervention groups and one control
      group. Patients must be 70 years or older with a long-term illness or with
      unscheduled hospitalisation in the past 3 months (750 patients planned). This
      study involves volunteering GPs practising in French primary care centres, with
      randomisation at the practice level. The multifaceted interventions for
      interventional arms comprise an educational interactive multiprofessional seminar
      for GPs and nurses, a geriatric hotline dedicated to GPs in case of difficulties
      and the performance of a CGA updated to primary care. The CGA is systematically
      performed by a nurse in arm 1 but is GP-led on a case-by-case basis in arm 2. The
      primary endpoint is a composite criterion comprising overall death, unscheduled
      hospitalisations, emergency admissions and institutionalisation within 12 months
      after inclusion. Intention-to-treat analysis will be performed using mixed
      effects logistic regression models, with adjustment for potential confounders.
      ETHICS AND DISSEMINATION: The protocol was approved by an appropriate ethics
      committee (CPP Ile-de-France IV, Paris, France, approval April 2015;15 664). This
      study is conducted according to principles of good clinical practice in the
      context of current care and will provide useful knowledge on the clinical
      benefits achievable by CGA in primary care. TRIAL REGISTRATION NUMBER:
      NCT02664454; Pre-results.

PMID- 29654039
TI  - Randomised controlled feasibility trial of standard wound management versus
      negative-pressure wound therapy in the treatment of adult patients having
      surgical incisions for hip fractures.
AB  - INTRODUCTION: Deep wound infection is a catastrophic complication after hip
      fracture surgery. However, current understanding of infection rates in this
      population is limited. Many technologies such as incisional negative-pressure
      wound therapy (NPWT) show promise in reducing the rate of infection. This trial
      is a feasibility study looking to establish a value estimated with a greater
      precision of the rate of deep infection after hip fracture treatment in patients
      treated with NPWT versus standard dressing following hip fracture surgery.
      METHODS AND ANALYSIS: A randomised controlled trial of 464 patients will be run
      across multiple centres. It is embedded in the World Hip Trauma Evaluation cohort
      study. Any patient over the age of 65 years having surgery for hip fracture is
      eligible unless they are being treated with percutaneous screw fixation. A web
      based randomisation sequence will stratify patients by centre. Patients will be
      allocated to either NPWT or standard care on a 1:1 basis. The primary outcome
      measure is the Centre for Disease Control definition of deep infection at 30
      days. Follow-up at 4 months will also assess deep infection and the core outcome
      dataset for hip fractures. This includes health-related quality of life (EQ-5D
      5L), mobility, mortality and late complications such as further surgery. The
      primary analysis will be intention to treat. ETHICS AND DISSEMINATION: Oxford C
      Research Ethics Committee granted ethical approval on 28/04/2017, 17/SC/0207. The
      results of this study will be reported in a peer-reviewed publication and inform
      the design of a future full-scale trial. TRIAL REGISTRATION NUMBER:
      ISRCTN55305726.

PMID- 29654041
TI  - Is there an association between nurse, clinical teacher and peer feedback for
      trainee doctors' medical specialty choice? An observational study in Taiwan.
AB  - OBJECTIVES: This study explored whether there is an association between medical
      trainees' future specialty choices and the 360-degree feedback they receive. We
      hypothesised that the higher the scores that teachers, trainees and/or nurses
      give to postgraduate year 1s (PGY1s) in any given specialty, the more likely that
      they will choose that specialty for their residency. SETTING: The study was
      conducted in a large regional teaching hospital in Taiwan. PARTICIPANTS: The
      participants of this study were n=66 PGY1s who had completed their medical
      studies domestically or internationally and had received their PGY1 training in a
      single teaching hospital in southern Taiwan. Data from 990 assessments were
      included. PRIMARY AND SECONDARY OUTCOME MEASURES: Logistic regression analyses
      for teachers', nursing staff and peers' authentic assessments of trainees were
      undertaken for (1) desired specialty, (2) applied specialty, (3) enrolled
      specialty, (4) consistency between desired and applied specialties, (5)
      consistency between applied and enrolled specialties and (6) consistency between
      desired and enrolled specialties. Alpha was set at p<0.05. RESULTS: Nursing staff
      scores were significantly associated with all six dependent variables.
      Furthermore, teachers' scores were significantly associated with trainees'
      desired specialty and the consistency between desired and enrolled specialty.
      Peers' scores were not significantly associated with any dependent variable.
      CONCLUSIONS: Trainees' specialty choices are associated with scores given by
      nursing staff and clinical teachers. We suggest that qualitative research methods
      should further explore this association to ascertain whether PGY1s are
      consciously influenced by these scores and if so, in what way.

PMID- 29654040
TI  - The role of psychological factors in the perpetuation of pain intensity and
      disability in people with chronic shoulder pain: a systematic review.
AB  - INTRODUCTION: Chronic shoulder pain is a very complex syndrome, and the
      mechanisms involved in its perpetuation remain unclear. Psychological factors
      appear to play a role in the perpetuation of symptoms in people with shoulder
      chronicity. The purpose of this systematic review is to examine the role of
      psychological factors in the perpetuation of symptoms (pain intensity and
      disability) in people with chronic shoulder pain. METHODS AND ANALYSIS: A
      systematic search was performed on PubMed, AMED, CINAHL, PubPsych and EMBASE from
      inception to July 2017. Longitudinal studies with quantitative designs analysing
      the role of psychological factors on pain intensity, disability or both were
      included. The methodological quality of the included studies was evaluated with
      an adapted version of the Newcastle Ottawa Scale. The level of evidence per
      outcome was examined using the Grading of Recommendations Assessment, Development
      and Evaluation approach. RESULTS: A total of 27 articles were included with a
      sample of 11 176 people with chronic shoulder pain. The risk of bias ranges from
      7/21 to 13/21 across the studies. The quality of the evidence was very low. High
      levels of self-efficacy, resilience and expectations of recovery were
      significantly associated with low levels of pain intensity and disability.
      Inversely, high levels of emotional distress, depressive symptoms, anxiety,
      preoperative concerns, fear-avoidance beliefs, somatisation and pain
      catastrophising were significantly associated with high levels of pain intensity
      and disability. DISCUSSION: Our results suggest that psychological factors may
      influence the perpetuation of pain intensity and disability, with very low
      evidence. A meta-analysis was not carried out due to the heterogeneity of the
      included studies so results should be interpreted with caution. PROSPERO TRIAL
      REGISTRATION NUMBER: CRD42016036366.

PMID- 29654042
TI  - Influence of the Scandinavian climate pattern on the UK asthma mortality: a time
      series and geospatial study.
AB  - OBJECTIVE: It is well known that climate variability and trends have an impact on
      human morbidity and mortality, especially during the winter. However, there are
      only a handful of studies that have undertaken quantitative investigations into
      this impact. We evaluate the association between the UK winter asthma mortality
      data to a well-established feature of the climate system, the Scandinavian (SCA)
      pattern. METHODS: Time series analysis of monthly asthma mortality through the
      period of January 2001 to December 2015 was conducted, where the data were
      acquired from the UK's Office for National Statistics. The correlations between
      indices of important modes of climate variability impacting the UK such as the
      North Atlantic Oscillation as well as the SCA and the asthma mortality time
      series were computed. A grid point correlation analysis was also conducted with
      the asthma data with sea level pressure, surface wind and temperature data
      acquired from the European Centre for Medium-Range Weather Forecasts. RESULTS: We
      find that sea level pressure and temperature fluctuations associated with the SCA
      explain ~20% (>95% CL) of variance in the UK asthma mortality through a period of
      2001-2015. Furthermore, the highest winter peak in asthma mortality occurred in
      the year 2015, during which there were strong northwesterly winds over the UK
      that were the result of a sea level pressure pattern similar to that associated
      with the SCA. CONCLUSIONS: Our study emphasises the importance of incorporating
      large-scale geospatial analyses into future research of understanding diseases
      and its environmental impact on human health.

PMID- 29654043
TI  - Pregnancy outcomes among Chinese women with and without systemic lupus
      erythematosus: a retrospective cohort study.
AB  - OBJECTIVE: To completely and quantifiably determine the effect of systemic lupus
      erythematosus (SLE) on pregnancy outcomes in a Chinese cohort. DESIGN: A
      retrospective cohort study. SETTING: Data were collected at a tertiary medical
      centre located in Shanghai, China, from September 2011 to May 2017. PARTICIPANTS:
      We assigned 338 pregnant women with SLE to the study cohort and 1014 randomly
      selected pregnant women without SLE (three for every woman with SLE) to a
      comparison cohort. The relevant medical records of all pregnant women were
      retrospectively reviewed. Cases of multiple pregnancy and cases in which an
      artificial abortion was performed for personal reasons were excluded. PRIMARY AND
      SECONDARY OUTCOME MEASURES: Maternal and fetal outcomes were primary outcomes,
      and management of antenatal care was the secondary outcome. RESULTS: The risks of
      pregnancy-induced hypertension (OR 2.68, 95% CI 1.75 to 4.09), pre-eclampsia (OR
      3.13, 95% CI 1.95 to 5.03) and premature rupture of membranes (OR 2.53, 95% CI
      1.46 to 4.40) were significantly different between women with and without SLE.
      Gestational diabetes was negatively associated with SLE in pregnant women (OR
      0.49, 95% CI 0.28 to 0.85). Pregnant women with SLE displayed significantly
      higher rates of fetal loss (OR 10.23, 95% CI 5.08 to 20.59), including
      spontaneous abortion (OR 4.42, 95% CI 1.52 to 12.80), therapeutic abortion (OR
      16.57, 95% CI 5.80 to 47.35) and stillbirth (OR 13.25, 95% CI 1.49 to 118.11),
      and a higher risk of preterm birth (OR 3.15, 95% CI 2.21 to 4.50), intrauterine
      growth restriction (OR 2.20, 95% CI 1.35 to 3.58), a child who was small for the
      gestational age (OR 1.86, 95% CI 1.11 to 3.13), a caesarean section (OR 4.73, 95%
      CI 3.30 to 6.80) or a neonatal intensive care unit admission (OR 3.48, 95% CI
      2.21 to 5.48) than women in the non-SLE population after adjusting for
      confounding factors. CONCLUSIONS: In this study, SLE significantly increased the
      risk of adverse pregnancy outcomes. Therefore, a preconception assessment and
      close antenatal monitoring by both rheumatologists and obstetricians should be
      performed in pregnant women with SLE.

PMID- 29654044
TI  - Association between depressive symptoms and objectively measured daily step count
      in individuals at high risk of cardiovascular disease in South London, UK: a
      cross-sectional study.
AB  - OBJECTIVES: Depressive symptoms are common but rarely considered a risk factor
      for unhealthy lifestyles associated with cardiovascular disease (CVD). This study
      investigates whether depressive symptoms are associated with reduced physical
      activity (PA) in individuals at high risk of developing CVD. DESIGN: Secondary
      analysis of the cross-sectional baseline data from a randomised controlled trial
      of an intensive lifestyle intervention. SETTING: 135 primary care practices in
      South London, UK. PARTICIPANTS: 1742 adults, 49-74 years, 86% male at high
      (>=20%) risk of developing CVD in the next 10 years as defined via QRISK2 score.
      OUTCOME MEASURES: The main explanatory variable was depressive symptoms measured
      via the Patient Health Questionnaire-9 (PHQ-9). The main outcome was daily step
      count measured with an accelerometer (ActiGraph GT3X) stratified by weekdays and
      weekend days. RESULTS: The median daily step count of the total sample was 6151
      (IQR 3510) with significant differences (P<0.001) in mean daily step count
      between participants with low (PHQ-9 score: 0-4), mild (PHQ-9 score: 5-9) and
      moderate to severe depressive symptoms (PHQ-9 score: >=10). Controlling for age,
      gender, ethnicity, education level, body mass index (BMI), smoking, consumption
      of alcohol, day of the week and season, individuals with mild depressive symptoms
      and those with moderate to severe depressive symptoms walked 13.3% (95% CI 18.8%
      to 7.9%) and 15.6% (95% CI 23.7% to 6.5%) less than non-depressed individuals,
      respectively. Furthermore, male gender, white ethnicity, higher education level,
      lower BMI, non-smoking, moderate alcohol intake, weekdays and summer season were
      independently associated with higher step count. CONCLUSIONS: People at high risk
      of CVD with depressive symptoms have lower levels of PA. TRIAL REGISTRATION:
      ISRCTN84864870; Pre-results.

PMID- 29654045
TI  - Study protocol for a randomised controlled trial examining the association
      between physical activity and sleep quality in children with autism spectrum
      disorder based on the melatonin-mediated mechanism model.
AB  - INTRODUCTION: Sleep disturbance is commonly observed in children with autism
      spectrum disorders (ASD). Disturbed sleep may exacerbate the core symptoms of
      ASD. Behavioural interventions and supplemental melatonin medication are
      traditionally used to improve sleep quality, but poor sustainability of
      behavioural intervention effects and use of other medications that metabolise
      melatonin may degrade the effectiveness of these interventions. However, several
      studies have suggested that physical activity may provide an effective
      intervention for treating sleep disturbance in typically developing children.
      Thus, we designed a study to examine whether such an intervention is also
      effective in children with ASD. We present a protocol (4 December 2017) for a
      jogging intervention with a parallel and two-group randomised controlled trial
      design using objective actigraphic assessment and 6-sulfatoxymelatonin
      measurement to determine whether a 12-week physical activity intervention elicits
      changes in sleep quality or melatonin levels. METHODS AND ANALYSIS: All eligible
      participants will be randomly allocated to either a jogging intervention group or
      a control group receiving standard care. Changes in sleep quality will be
      monitored through actigraphic assessment and parental sleep logs. All
      participants will also be instructed to collect a 24-hour urine sample. 6
      sulfatoxymelatonin, a creatinine-adjusted morning urinary melatonin
      representative of the participant's melatonin levels, will be measured from the
      sample. All assessments will be carried out before the intervention (T1),
      immediately after the 12-week intervention or regular treatment (T2), 6 weeks
      after the intervention (T3) and 12 weeks after the intervention (T4) to examine
      the sustainability of the intervention effects. The first enrolment began in
      February 2018. ETHICS AND DISSEMINATION: Ethical approval was obtained through
      the Human Research Ethics Committee, Education University of Hong Kong. The
      results of this trial will be submitted for publication in peer-reviewed
      journals. TRIAL REGISTRATION NUMBER: NCT03348982.

PMID- 29654046
TI  - Children and Young People-Mental Health Safety Assessment Tool (CYP-MH SAT)
      study: Protocol for the development and psychometric evaluation of an assessment
      tool to identify immediate risk of self-harm and suicide in children and young
      people (10-19 years) in acute paediatric hospital settings.
AB  - INTRODUCTION: Currently, no standardised, evidence-based assessment tool for
      assessing immediate self-harm and suicide in acute paediatric inpatient settings
      exists. AIM: The aim of this study is to develop and test the psychometric
      properties of an assessment tool that identifies immediate risk of self-harm and
      suicide in children and young people (10-19 years) in acute paediatric hospital
      settings. METHODS AND ANALYSIS: Development phase: This phase involved a scoping
      review of the literature to identify and extract items from previously published
      suicide and self-harm risk assessment scales. Using a modified electronic Delphi
      approach, these items will then be rated according to their relevance for
      assessment of immediate suicide or self-harm risk by expert professionals.
      Inclusion of items will be determined by 65%-70% consensus between raters.
      Subsequently, a panel of expert members will convene to determine the face
      validity, appropriate phrasing, item order and response format for the finalised
      items.Psychometric testing phase: The finalised items will be tested for validity
      and reliability through a multicentre, psychometric evaluation. Psychometric
      testing will be undertaken to determine the following: internal consistency,
      inter-rater reliability, convergent, divergent validity and concurrent validity.
      ETHICS AND DISSEMINATION: Ethical approval was provided by the National Health
      Service East Midlands-Derby Research Ethics Committee (17/EM/0347) and full
      governance clearance received by the Health Research Authority and local
      participating sites. Findings from this study will be disseminated to
      professionals and the public via peer-reviewed journal publications, popular
      social media and conference presentations.

PMID- 29654047
TI  - Binge drinking and associated factors among school students: a cross-sectional
      study in Zhejiang Province, China.
AB  - OBJECTIVE: To investigate the prevalence and correlating factors of binge
      drinking among middle and high school students in Zhejiang Province, China.
      METHODS: We performed a cross-sectional study using data from a school-based
      survey. A total of 23 543 (response rate=97.5%) eligible adolescents from 442
      different schools (including middle schools, academic high schools and vocational
      high schools) were asked to fill in an anonymous self-administered behaviour
      questionnaire between April and May 2017. Multivariable logistic regression
      models were used to examine the associations of sociodemographic and behavioural
      factors with binge drinking. RESULTS: The mean (SD) age of participants was 15.6
      (1.7) years and 51.3% were boys. The proportions of students from middle schools,
      academic high schools and vocational high schools were 51.9%, 27.5% and 20.6%,
      respectively. In total, 22.8% (95% CI 21.6 to 23.9) of students reported drinking
      alcohol in the past 30 days and 9.2% (95% CI 8.5 to 10.0) of students reported
      binge drinking (defined as drinking four or more alcoholic drinks in 1-2 hours
      period among girls and five or more alcoholic drinks among boys) during the past
      month. The prevalence of binge drinking was highest among vocational high school
      students (17.9% vs 6.3% and 7.7% among middle school and academic high school
      students, respectively). Older age, studying at high school, poor academic
      performance, higher levels of physical activity, excessive screen-time,
      loneliness, insomnia, previous suicide attempt, cigarette smoking, fighting,
      being bullied and sexual experience were found to be positively associated with
      adolescent binge drinking. CONCLUSIONS: Binge drinking is common among middle and
      high school students in Zhejiang, China. Efforts to prevent binge drinking may
      need to address a cluster of sociodemographic and behavioural factors. Our
      findings provide information to enable healthcare providers to identify students
      at high-risk of binge drinking and to inform planning of intervention measures
      for at-risk students.

PMID- 29654048
TI  - The validity of the Rx-Risk Comorbidity Index using medicines mapped to the
      Anatomical Therapeutic Chemical (ATC) Classification System.
AB  - OBJECTIVES: To provide a map of Anatomical Therapeutic Chemical (ATC)
      Classification System codes to individual Rx-Risk comorbidities and to validate
      the Rx-Risk Comorbidity Index. DESIGN: The 46 comorbidities in the Rx-Risk Index
      were mapped to dispensing's indicative of each condition using ATC codes.
      Prescription dispensing claims in 2014 were used to calculate the Rx-Risk. A
      baseline logistic regression model was fitted using age and gender as covariates.
      Rx-Risk was added to the base model as an (1) unweighted score, (2) weighted
      score and as (3) individual comorbidity categories indicating the presence or
      absence of each condition. The Akaike information criterion and c-statistic were
      used to compare the models. SETTING: Models were developed in the Australian
      Government Department of Veterans' Affairs health claims data, and external
      validation was undertaken in a 10% sample of the Australian Pharmaceutical
      Benefits Scheme Data. PARTICIPANTS: Subjects aged 65 years or older. OUTCOME
      MEASURES: Death within 1 year (eg, 2015). RESULTS: Compared with the base model
      (c-statistic 0.738, 95% CI 0.734 to 0.742), including Rx-Risk improved prediction
      of mortality; unweighted score 0.751, 95% CI 0.747 to 0.754, weighted score
      0.786, 95% CI 0.782 to 0.789 and individual comorbidities 0.791, 95% CI 0.788 to
      0.795. External validation confirmed the utility of the weighted index (c
      statistic=0.833). CONCLUSIONS: The updated Rx-Risk Comorbidity Score was
      predictive of 1-year mortality and may be useful in practice to adjust for
      confounding in observational studies using medication claims data.

PMID- 29654050
TI  - Enhancing the quality and safety of care through training generalist doctors: a
      longitudinal, mixed-methods study of a UK broad-based training programme.
AB  - OBJECTIVE: Changing patient demographics make it ever more challenging to
      maintain the quality and safety of care. One approach to addressing this is the
      development of training for generalist doctors who can take a more holistic
      approach to care. The purpose of the work we report here is to consider whether a
      broad-based training programme prepares doctors for a changing health service.
      SETTING AND PARTICIPANTS: We adopted a longitudinal, mixed-methods approach,
      collecting questionnaire data from trainees on the broad-based training (BBT)
      programme in England (baseline n=62) and comparator trainees in the same regions
      (baseline n=90). We held 15 focus groups with BBT trainees and one-to-one
      telephone interviews with trainees post-BBT (n=21) and their Educational
      Supervisors (n=9). RESULTS: From questionnaire data, compared with comparator
      groups, BBT trainees were significantly more confident that their training would
      result in: wider perspectives, understanding specialty complementarity, ability
      to apply learning across specialties, manage complex patients and provide patient
      focused care. Data from interviews and focus groups provided evidence of positive
      consequences for patient care from BBT trainees' ability to apply knowledge from
      other specialties. Specifically, insights from BBT enabled trainees to tailor
      referrals and consider patients' psychological as well as physical needs, thus
      adopting a more holistic approach to care. Unintended consequences were revealed
      in focus groups where BBT trainees expressed feelings of isolation. However, when
      we explored this sentiment on questionnaire surveys, we found that at least as
      many in the comparator groups sometimes felt isolated. CONCLUSIONS: Practitioners
      with an understanding of care across specialty boundaries can enhance patient
      care and reduce risks from poor inter-specialty communication. Internationally,
      there is growing recognition of the place of generalism in medical practice and
      the need to take a more person-centred approach. Broad-based approaches to
      training support the development of generalist doctors, which is well-suited to a
      changing health service.

PMID- 29654051
TI  - Sensitivity of fasting glucose for gestational diabetes mellitus screening in
      Mexican adolescents based on International Association of Diabetes and Pregnancy
      Study Groups criteria: a diagnostic accuracy study based on retrospective data
      analysis.
AB  - OBJECTIVE: To evaluate fasting plasma glucose (FPG) as a screening test for
      gestational diabetes mellitus (GDM) among Mexican adolescents using International
      Association of Diabetes and Pregnancy Study Groups criteria. DESIGN:
      Retrospective cohort study. SETTING: Level-three medical institution in Mexico
      City. PARTICIPANTS: The study population comprised 1061 adolescent women aged 12
      19 years with singleton pregnancies, who underwent a 75 g oral glucose tolerance
      test (OGTT) between 11 and 35 weeks of gestation. PRIMARY AND SECONDARY OUTCOME
      MEASURES: The sensitivity (Sn), specificity (Sp), positive and negative
      predictive values (PPV and NPV, respectively), and positive and negative
      likelihood ratios LR (+) and LR (-), respectively) with 95% CIs for selected FPG
      cut-off values were compared. Secondary measures were perinatal outcomes in women
      with and without GDM. RESULTS: GDM was present in 71 women (6.7%, 95% CI 5.3% to
      8.4%). The performances of FPG at thresholds of >=80 (4.5 mmol/L), 85 (4.7
      mmol/L) and 90 mg/dL (5.0 mmol/L) were as follow (95% CI): Sn: 97% (89% to 99%),
      94% (86% to 97%) and 91% (82% to 95%); Sp: 50% (47% to 53%), 79% (76% to 81%) and
      97% (95% to 97%); PPV: 12% (9% to 15%), 23% (18% to 28%) and 64% (54% to 73%);
      NPV: 99% (98.5% to 99.9%) for all three cut-offs; LR (+): 1.9 (1.8 to 2.1), 4.3
      (3.8 to 5.0) and 26.7 (18.8 to 37.1) and LR (-): 0.06 (0.02 to 0.23), 0.07 (0.03
      to 0.19) and 0.09 (0.04 to 0.19), respectively. No significant differences in
      perinatal outcomes were found between adolescents with and without GDM.
      CONCLUSIONS: An FPG cut-off of >=90 mg/dL (5.0 mmol/L) is ideal for GDM screening
      in Mexican adolescent women. An FPG threshold of 90 mg/dL would miss 6 (8.5%)
      women with GDM, pick up 34 (3.4%) women without GDM and avoid 962 (90.7%) OGTTs.

PMID- 29654052
TI  - 'Re-engage' pilot study protocol: a nurse-led eHealth intervention to re-engage,
      educate and empower childhood cancer survivors.
AB  - INTRODUCTION: Many childhood cancer survivors are disengaged from cancer-related
      follow-up care despite being at high risk of treatment-related late effects.
      Innovative models of long-term follow-up (LTFU) care to manage ongoing treatment
      related complications are needed. 'Re-engage' is a nurse-led eHealth intervention
      designed to improve survivors' health-related self-efficacy, targeted at
      survivors disengaged from follow-up. Re-engage aims to overcome survivor- and
      parent-reported barriers to care and ensure survivors receive the care most
      appropriate to their risk level. METHODS AND ANALYSIS: This study will recruit 30
      Australian childhood cancer survivors who are not receiving any cancer-related
      care. Participation involves two online/telephone consultations with a
      survivorship nurse for medical assessment, a case review, risk stratification and
      creation of a care plan by a multidisciplinary team of specialists. We will
      assess the feasibility of implementing 'Re-engage' and its acceptability to
      participants and health professionals involved. The primary outcome will be
      survivors' health-related self-efficacy, measured at baseline and 1 and 6 months
      postintervention. Secondary outcomes will include the effect of 'Re-engage' on
      survivors' health behaviours and beliefs, engagement in healthcare, information
      needs and emotional well-being. We will also document the cost per patient to
      deliver 'Re-engage'. If Re-engage is acceptable, feasible and demonstrates early
      efficacy, it may have the potential to empower survivors in coordinating their
      complex care, improving survivors' long-term engagement and satisfaction with
      care. Ideally, it will be implemented into clinical practice to recall survivors
      lost to follow-up and reduce the ongoing burden of treatment for childhood
      cancer. ETHICS AND DISSEMINATION: The study protocol has been approved by the
      South Eastern Sydney Local Health District Human Research Ethics Committee
      (reference number: 16/366). The results will be disseminated in peer-reviewed
      journals and at scientific conferences. A lay summary will be published on the
      Behavioural Sciences Unit website. TRIAL REGISTRATION NUMBER:
      ACTRN12618000194268.

PMID- 29654053
TI  - Comparative effectiveness of treatments to prevent dental caries given to rural
      children in school-based settings: protocol for a cluster randomised controlled
      trial.
AB  - INTRODUCTION: Dental caries is the most prevalent childhood disease in the world
      and can lead to infection, pain and reduced quality of life. Multiple prevention
      agents are available to arrest and prevent dental caries; however, little is
      known of the comparative effectiveness of combined treatments when applied in
      pragmatic settings. The aim of the presented study is to compare the benefit of
      silver diamine fluoride and fluoride varnish versus fluoride varnish and glass
      ionomer therapeutic sealants in the arrest and prevention of dental caries.
      METHODS AND ANALYSIS: A longitudinal, pragmatic, cluster randomised, single
      blind, non-inferiority trial will be conducted in low-income rural children
      enrolled in public elementary schools in New Hampshire, USA, from 2018 to 2023.
      The primary objective is to compare the non-inferiority of alternative agents in
      the arrest and prevention of dental caries. The secondary objective is to compare
      cost-effectiveness of both interventions. Caries arrest will be evaluated after 2
      years, and caries prevention will be assessed at the completion of the study.
      Data analysis will follow intent to treat, and statistical analyses will be
      conducted using a significance level of 0.05. ETHICS AND DISSEMINATION: The
      standard of care for dental caries is office-based surgery, which presents
      multiple barriers to care including cost, fear and geographic isolation. The
      common intervention used in school-based caries prevention is dental sealants.
      The simplicity and affordability of silver diamine fluoride may be a viable
      alternative for the prevention of dental caries in high-risk children. Results
      can be used to inform policy for best practices in school-based oral healthcare.
      TRIAL REGISTRATION: NCT03448107. Pre-results.

PMID- 29654049
TI  - Study protocol to assess the effectiveness and safety of a flexible family
      visitation model for delirium prevention in adult intensive care units: a cluster
      randomised, crossover trial (The ICU Visits Study).
AB  - INTRODUCTION: Flexible intensive care unit (ICU) visiting hours have been
      proposed as a means to improve patient-centred and family-centred care. However,
      randomised trials evaluating the effects of flexible family visitation models
      (FFVMs) are scarce. This study aims to compare the effectiveness and safety of an
      FFVM versus a restrictive family visitation model (RFVM) on delirium prevention
      among ICU patients, as well as to analyse its potential effects on family members
      and ICU professionals. METHODS AND ANALYSIS: A cluster-randomised crossover trial
      involving adult ICU patients, family members and ICU professionals will be
      conducted. Forty medical-surgical Brazilian ICUs with RFVMs (<4.5 hours/day) will
      be randomly assigned to either an RFVM (visits according to local policies) or an
      FFVM (visitation during 12 consecutive hours per day) group at a 1:1 ratio. After
      enrolment and follow-up of 25 patients, each ICU will be switched over to the
      other visitation model, until 25 more patients per site are enrolled and
      followed. The primary outcome will be the cumulative incidence of delirium among
      ICU patients, measured twice a day using the Confusion Assessment Method for the
      ICU. Secondary outcome measures will include daily hazard of delirium, ventilator
      free days, any ICU-acquired infections, ICU length of stay and hospital mortality
      among the patients; symptoms of anxiety and depression and satisfaction among the
      family members; and prevalence of burnout symptoms among the ICU professionals.
      Tertiary outcomes will include need for antipsychotic agents and/or mechanical
      restraints, coma-free days, unplanned loss of invasive devices and ICU-acquired
      pneumonia, urinary tract infection or bloodstream infection among the patients;
      self-perception of involvement in patient care among the family members; and
      satisfaction among the ICU professionals. ETHICS AND DISSEMINATION: The study
      protocol has been approved by the research ethics committee of all participant
      institutions. We aim to disseminate the findings through conferences and peer
      reviewed journals. TRIAL REGISTRATION: NCT02932358.

PMID- 29654054
TI  - Correction: Role of the family doctor in the management of adults with obesity: a
      scoping review.

PMID- 29654055
TI  - Correction: Fetal alcohol spectrum disorder and youth justice: a prevalence study
      among young people sentenced to detention in Western Australia.

PMID- 29654056
TI  - Divided views rule implementation of integrated care.

PMID- 29654057
TI  - Platelets expressing IgG receptor FcgammaRIIA/CD32A determine the severity of
      experimental anaphylaxis.
AB  - Platelets are key regulators of vascular integrity; however, their role in
      anaphylaxis, a life-threatening systemic allergic reaction characterized by the
      loss of vascular integrity and vascular leakage, remains unknown. Anaphylaxis is
      a consequence of inappropriate cellular responses triggered by antibodies to
      generally harmless antigens, resulting in a massive mediator release and rapidly
      occurring organ dysfunction. Human platelets express receptors for immunoglobulin
      G (IgG) antibodies and can release potent mediators, yet their contribution to
      anaphylaxis has not been previously addressed in mouse models, probably because
      mice do not express IgG receptors on platelets. We investigated the contribution
      of platelets to IgG-dependent anaphylaxis in human IgG receptor-expressing mouse
      models and a cohort of patients suffering from drug-induced anaphylaxis. Platelet
      counts dropped immediately and markedly upon anaphylaxis induction only when they
      expressed the human IgG receptor FcgammaRIIA/CD32A. Platelet depletion attenuated
      anaphylaxis, whereas thrombocythemia substantially worsened its severity.
      FcgammaRIIA-expressing platelets were directly activated by IgG immune complexes
      in vivo and were sufficient to restore susceptibility to anaphylaxis in resistant
      mice. Serotonin released by activated platelets contributed to anaphylaxis
      severity. Data from a cohort of patients suffering from drug-induced anaphylaxis
      indicated that platelet activation was associated with anaphylaxis severity and
      was accompanied by a reduction in circulating platelet numbers. Our findings
      identify platelets as critical players in IgG-dependent anaphylaxis and provide a
      rationale for the design of platelet-targeting strategies to attenuate the
      severity of anaphylactic reactions.

PMID- 29654058
TI  - Intramuscular tendon injury is not associated with an increased hamstring
      reinjury rate within 12 months after return to play.
AB  - BACKGROUND: Acute hamstring injury that includes intramuscular tendon injury has
      been suggested to be associated with increased reinjury risk. These observations
      were based on a relatively small number of retrospectively analysed cases.
      OBJECTIVE: To determine whether intramuscular tendon injury is associated with
      higher reinjury rates in acute hamstring injury. METHODS: MRIs of 165 athletes
      with an acute hamstring injury were obtained within 5 days of injury. Treatment
      consisted of a standardised criteria-based rehabilitation programme. Standardised
      MRI parameters and intramuscular tendon injury, the latter subdivided into tendon
      disruption and waviness, were scored. We prospectively recorded reinjuries,
      defined as acute onset of posterior thigh pain in the same leg within 12 months
      after return to play. RESULTS: Participants were predominantly football players
      (72%). Sixty-four of 165 (39%) participants had an index injury with
      intramuscular hamstring tendon disruption, and waviness was present in 37 (22%).
      In total, there were 32 (19%) reinjuries. There was no significant difference
      (HR: 1.05, 95% CI 0.52 to 2.12, P=0.898) in reinjury rate between index injuries
      with intramuscular tendon disruption (n=13, 20%) and without tendon disruption
      (n=19, 20%). There was no significant difference in reinjury rate (X2(1)=0.031,
      P=0.861) between index injuries with presence of waviness (n=7, 19%) and without
      presence of waviness (n=25, 20%). CONCLUSION: In athletes with an acute hamstring
      injury, intramuscular tendon injury was not associated with an increased reinjury
      rate within 12 months after return to play.

PMID- 29654059
TI  - Transcriptional coactivator PGC-1alpha contains a novel CBP80-binding motif that
      orchestrates efficient target gene expression.
AB  - Although peroxisome proliferator-activated receptor-gamma (PPARgamma) coactivator
      1alpha (PGC-1alpha) is a well-established transcriptional coactivator for the
      metabolic adaptation of mammalian cells to diverse physiological stresses, the
      molecular mechanism by which it functions is incompletely understood. Here we
      used in vitro binding assays, X-ray crystallography, and immunoprecipitations of
      mouse myoblast cell lysates to define a previously unknown cap-binding protein 80
      (CBP80)-binding motif (CBM) in the C terminus of PGC-1alpha. We show that the
      CBM, which consists of a nine-amino-acid alpha helix, is critical for the
      association of PGC-1alpha with CBP80 at the 5' cap of target transcripts. Results
      from RNA sequencing demonstrate that the PGC-1alpha CBM promotes RNA synthesis
      from promyogenic genes. Our findings reveal a new conduit between DNA-associated
      and RNA-associated proteins that functions in a cap-binding protein surveillance
      mechanism, without which efficient differentiation of myoblasts to myotubes fails
      to occur.

PMID- 29654061
TI  - 100 years of STIs in the UK: a review of national surveillance data.
AB  - OBJECTIVES: The 1916 Royal Commission on Venereal Diseases was established in
      response to epidemics of syphilis and gonorrhoea in the UK. In the 100 years
      since the Venereal Diseases Act (1917), the UK has experienced substantial
      scientific, economic and demographic changes. We describe historical and recent
      trends in STIs in the UK. METHODS: We analysed surveillance data derived from STI
      clinics' statistical returns from 1917 to 2016. RESULTS: Since 1918, gonorrhoea
      and syphilis diagnoses have fluctuated, reflecting social, economic and
      technological trends. Following spikes after World Wars I and II, rates declined
      before re-emerging during the 1960s. At that time, syphilis was more common in
      men, suggestive of transmission within the men who have sex with men (MSM)
      population. Behaviour change following the emergence of HIV/AIDS in the 1980s is
      thought to have facilitated a precipitous decline in diagnoses of both STIs in
      the mid-1980s. Since the early 2000s, gonorrhoea and syphilis have re-emerged as
      major public health concerns due to increased transmission among MSM and the
      spread of antimicrobial-resistant gonorrhoea. Chlamydia and genital warts are now
      the most commonly diagnosed STIs in the UK and have been the focus of public
      health interventions, including the national human papillomavirus vaccination
      programme, which has led to substantial declines in genital warts in young
      people, and the National Chlamydia Screening Programme in England. Since the
      1980s, MSM, black ethnic minorities and young people have experienced the highest
      STI rates. CONCLUSION: Although diagnoses have fluctuated over the last century,
      STIs continue to be an important public health concern, often affecting more
      marginalised groups in society. Prevention must remain a public health priority
      and, as we enter a new era of sexual healthcare provision including online
      services, priority must be placed on maintaining prompt access for those at
      greatest risk of STIs.

PMID- 29654060
TI  - RNAi drives nonreciprocal translocations at eroding chromosome ends to establish
      telomere-free linear chromosomes.
AB  - The identification of telomerase-negative HAATI (heterochromatin amplification
      mediated and telomerase-independent) cells, in which telomeres are superseded by
      nontelomeric heterochromatin tracts, challenged the idea that canonical telomeres
      are essential for chromosome linearity and raised crucial questions as to how
      such tracts translocate to eroding chromosome ends and confer end protection.
      Here we show that HAATI arises when telomere loss triggers a newly recognized
      illegitimate translocation pathway that requires RNAi factors. While RNAi is
      necessary for the translocation events that mobilize ribosomal DNA (rDNA) tracts
      to all chromosome ends (forming "HAATIrDNA" chromosomes), it is dispensable for
      HAATIrDNA maintenance. Surprisingly, Dicer (Dcr1) plays a separate, RNAi
      independent role in preventing formation of the rare HAATI subtype in which a
      different repetitive element (the subtelomeric element) replaces telomeres. Using
      genetics and fusions between shelterin components and rDNA-binding proteins, we
      mapped the mechanism by which rDNA loci engage crucial end protection factors
      despite the absence of telomere repeats-and secure end protection. Sequence
      analysis of HAATIrDNA genomes allowed us to propose RNA and DNA polymerase
      template-switching models for the mechanism of RNAi-triggered rDNA
      translocations. Collectively, our results reveal unforeseen roles for noncoding
      RNAs (ncRNAs) in assembling a telomere-free chromosome end protection device.

PMID- 29654062
TI  - Efficient Gene Silencing in Brain Tumors with Hydrophobically Modified siRNAs.
AB  - Glioblastoma (GBM) is the most common and lethal form of primary brain tumor with
      dismal median and 2-year survivals of 14.5 months and 18%, respectively. The
      paucity of new therapeutic agents stems from the complex biology of a highly
      adaptable tumor that uses multiple survival and proliferation mechanisms to
      circumvent current treatment approaches. Here, we investigated the potency of a
      new generation of siRNAs to silence gene expression in orthotopic brain tumors
      generated by transplantation of human glioma stem-like cells in athymic nude
      mice. We demonstrate that cholesterol-conjugated, nuclease-resistant siRNAs (Chol
      hsiRNAs) decrease mRNA and silence luciferase expression by 90% in vitro in GBM
      neurospheres. Furthermore, Chol-hsiRNAs distribute broadly in brain tumors after
      a single intratumoral injection, achieving sustained and potent (>45% mRNA and
      >90% protein) tumor-specific gene silencing. This readily available platform is
      sequence-independent and can be adapted to target one or more candidate GBM
      driver genes, providing a straightforward means of modulating GBM biology in
      vivoMol Cancer Ther; 17(6); 1251-8. (c)2018 AACR.

PMID- 29654063
TI  - A Short BRCA2-Derived Cell-Penetrating Peptide Targets RAD51 Function and Confers
      Hypersensitivity toward PARP Inhibition.
AB  - Under conditions of genotoxic stress, cancer cells strongly rely on efficient DNA
      repair to survive and proliferate. The human BRCA2 tumor suppressor protein is
      indispensable for the repair of DNA double-strand breaks by homologous
      recombination (HR) by virtue of its ability to promote RAD51 loading onto single
      stranded DNA. Therefore, blocking the interaction between BRCA2 and RAD51 could
      significantly improve the efficacy of conventional anticancer therapies. However,
      targeting protein-protein interaction (PPI) interfaces has proven challenging
      because flat and large PPI surfaces generally do not support binding of small
      molecule inhibitors. In contrast, peptides are more potent for targeting PPIs but
      are otherwise difficult to deliver into cells. Here, we report that a synthetic
      16-mer peptide derived from the BRC4 repeat motif of BRCA2 is capable of blocking
      RAD51 binding to BRCA2. Efficient noncytotoxic cellular uptake of a nona-arginine
      (R9)-conjugated version of the BRC4 peptide interferes with DNA damage-induced
      RAD51 foci formation and HR. Moreover, transduction of the BRC4 peptide impairs
      replication fork-protective function of BRCA2 and triggers MRE11-dependent
      degradation of nascent DNA in response to DNA replication stress. Finally, the
      BRC4 cell-penetrating peptide (CPP) confers selective hypersensitivity to PARP
      inhibition in cancer cells but spares noncancerous cells. Taken together, our
      data highlight an innovative approach to develop novel peptide-based DNA repair
      inhibitors and establish BRCA2-derived CPPs as promising anticancer agents. Mol
      Cancer Ther; 17(7); 1392-404. (c)2018 AACR.

PMID- 29654065
TI  - Induced Telomere Damage to Treat Telomerase Expressing Therapy-Resistant
      Pediatric Brain Tumors.
AB  - Brain tumors remain the leading cause of cancer-related deaths in children and
      often are associated with long-term sequelae among survivors of current
      therapies. Hence, there is an urgent need to identify actionable targets and to
      develop more effective therapies. Telomerase and telomeres play important roles
      in cancer, representing attractive therapeutic targets to treat children with
      poor-prognosis brain tumors such as diffuse intrinsic pontine glioma (DIPG), high
      grade glioma (HGG), and high-risk medulloblastoma. We have previously shown that
      DIPG, HGG, and medulloblastoma frequently express telomerase activity. Here, we
      show that the telomerase-dependent incorporation of 6-thio-2'deoxyguanosine (6
      thio-dG), a telomerase substrate precursor analogue, into telomeres leads to
      telomere dysfunction-induced foci (TIF) along with extensive genomic DNA damage,
      cell growth inhibition, and cell death of primary stem-like cells derived from
      patients with DIPG, HGG, and medulloblastoma. Importantly, the effect of 6-thio
      dG is persistent even after drug withdrawal. Treatment with 6-thio-dG elicits a
      sequential activation of ATR and ATM pathways and induces G2-M arrest. In vivo
      treatment of mice bearing medulloblastoma xenografts with 6-thio-dG delays tumor
      growth and increases in-tumor TIFs and apoptosis. Furthermore, 6-thio-dG crosses
      the blood-brain barrier and specifically targets tumor cells in an orthotopic
      mouse model of DIPG. Together, our findings suggest that 6-thio-dG is a promising
      novel approach to treat therapy-resistant telomerase-positive pediatric brain
      tumors. Mol Cancer Ther; 17(7); 1504-14. (c)2018 AACR.

PMID- 29654064
TI  - Antibody-Dependent Cellular Phagocytosis by Macrophages is a Novel Mechanism of
      Action of Elotuzumab.
AB  - Elotuzumab, a recently approved antibody for the treatment of multiple myeloma,
      has been shown to stimulate Fcgamma receptor (FcgammaR)-mediated antibody
      dependent cellular cytotoxicity by natural killer (NK) cells toward myeloma
      cells. The modulatory effects of elotuzumab on other effector cells in the tumor
      microenvironment, however, has not been fully explored. Antibody-dependent
      cellular phagocytosis (ADCP) is a mechanism by which macrophages contribute to
      antitumor potency of monoclonal antibodies. Herein, we studied the NK cell
      independent effect of elotuzumab on tumor-associated macrophages using a
      xenograft tumor model deficient in NK and adaptive immune cells. We demonstrate
      significant antitumor efficacy of single-agent elotuzumab in immunocompromised
      xenograft models of multiple myeloma, which is in part mediated by Fc-FcgammaR
      interaction of elotuzumab with macrophages. Elotuzumab is shown in this study to
      induce phenotypic activation of macrophages in vivo and mediates ADCP of myeloma
      cells though a FcgammaR-dependent manner in vitro Together, these findings
      propose a novel immune-mediated mechanism by which elotuzumab exerts anti-myeloma
      activity and helps to provide rationale for combination therapies that can
      enhance macrophage activity. Mol Cancer Ther; 17(7); 1454-63. (c)2018 AACR.

PMID- 29654066
TI  - Photodynamic Therapy Using Indocyanine Green Loaded on Super Carbonate Apatite as
      Minimally Invasive Cancer Treatment.
AB  - Minimally invasive treatment is getting more and more important in an aging
      society. The purpose of this study was to explore the possibility of ICG loaded
      on super carbonate apatite (sCA) nanoparticles as a novel photodynamic therapy
      (PDT) against cancers. Using colon cancer cells, ICG uptake and anti-tumor
      effects were examined between the treatments of ICG and sCA-ICG. Reactive oxygen
      species (ROS) production and temperature rise were also evaluated to explore the
      underlying mechanism. Atomic force microscopy revealed that the size of sCA-ICG
      ranged from 10 to 20 nm. In aqueous solution with 0.5% albumin, the temperature
      increase after laser irradiation was 27.1 degrees C and 23.1 degrees C in sCA-ICG
      and ICG, respectively (control DW: 5.7 degrees C). A significant increase in ROS
      generation was noted in cell cultures treated with sCA-ICG plus irradiation
      compared with those treated with ICG plus irradiation (P < 0.01). Uptake of ICG
      in the tumor cells significantly increased in sCA-ICG compared with ICG in vitro
      and in vivo The fluorescence signals of ICG in the tumor, liver, and kidney faded
      away in both treatments by 24 hours. Finally, the HT29 tumors treated with sCA
      ICG followed by irradiation exhibited drastic tumor growth retardation (P <
      0.01), whereas irradiation of tumors after injection of ICG did not inhibit tumor
      growth. This study shows that sCA is a useful vehicle for ICG-based PDT. Quick
      withdrawal of ICG from normal organs is unique to sCA-ICG and contrasts with the
      other nanoparticles remaining in normal organs for a long time. Mol Cancer Ther;
      17(7); 1613-22. (c)2018 AACR.

PMID- 29654067
TI  - Clinical Next-Generation Sequencing for Precision Oncology in Rare Cancers.
AB  - The European Society for Medical Oncology defines rare cancers as 5 or fewer
      cases per 100,000 persons per year. For many rare cancers, no standard of care
      exists, and treatment is often extrapolated. Identifying potentially targetable
      genomic alterations in rare tumors is a rational approach to improving treatment
      options. We sought to catalog these mutations in rare tumors and to assess their
      clinical utility.For this retrospective analysis, we selected rare tumor patients
      from a dataset of patients who underwent clinical tumor genomic profiling.
      Sarcomas were excluded. To index potentially actionable alterations, patients'
      reports were reviewed for mutations in cancer-associated genes and pathways.
      Respective clinical records were abstracted to appraise the benefit of using a
      targeted therapy approach. Actionable alterations were defined as targeted by a
      drug available on-label, off-label, or in clinical trials.The 95 patients
      analyzed had 40 different tumor subtypes, most common being adenoid cystic (13%),
      cholangiocarcinoma (7%), and metaplastic breast (6%). At least one genomic
      alteration was identified in 87 patients (92%). The most common identifiable
      mutations were in TP53 (23%), KRAS (10%), PIK3CA (9%), CDKN2A/B (8%), BRAF (7%),
      MLL (7%), and ARID1A (6%). Thirty-six patients (38%) with 21 different tumors had
      at least one potentially actionable alteration. Thirteen patients received
      targeted therapy. Of these, 4 had a partial response, 6 had stable disease, and 3
      had progressive disease as the best response.The addition of genomic profiling to
      management of rare cancers adds a potential line of therapy for cancers that have
      little or no standard of care. In our analysis, tumors with a BRAF alteration
      responded well to BRAF inhibitors. Mol Cancer Ther; 17(7); 1595-601. (c)2018
      AACR.

PMID- 29654069
TI  - Mechanistic Investigations of Diarrhea Toxicity Induced by Anti-HER2/3
      Combination Therapy.
AB  - Combination of targeted therapies is expected to provide superior efficacy in the
      treatment of cancer either by enhanced antitumor activity or by preventing or
      delaying the development of resistance. Common challenges in developing
      combination therapies include the potential of additive and aggravated toxicities
      associated with pharmacologically related adverse effects. We have recently
      reported that combination of anti-HER2 and anti-HER3 antibodies, pertuzumab and
      lumretuzumab, along with paclitaxel chemotherapy in metastatic breast cancer,
      resulted in a high incidence of diarrhea that ultimately limited further clinical
      development of this combination. Here, we further dissected the diarrhea profile
      of the various patient dose cohorts and carried out in vitro investigations in
      human colon cell lines and explants to decipher the contribution and the
      mechanism of anti-HER2/3 therapeutic antibodies to intestinal epithelium
      malfunction. Our clinical investigations in patients revealed that while dose
      reduction of lumretuzumab, omission of pertuzumab loading dose, and introduction
      of a prophylactic antidiarrheal treatment reduced most severe adverse events,
      patients still suffered from persistent diarrhea during the treatment. Our in
      vitro investigations showed that pertuzumab and lumretuzumab combination
      treatment resulted in upregulation of chloride channel activity without
      indication of intestinal barrier disruption. Overall, our findings provide a
      mechanistic rationale to explore alternative of conventional antigut motility
      using medication targeting chloride channel activity to mitigate diarrhea of HER
      combination therapies. Mol Cancer Ther; 17(7); 1464-74. (c)2018 AACR.

PMID- 29654068
TI  - RAS-MAPK Reactivation Facilitates Acquired Resistance in FGFR1-Amplified Lung
      Cancer and Underlies a Rationale for Upfront FGFR-MEK Blockade.
AB  - The FGFR kinases are promising therapeutic targets in multiple cancer types,
      including lung and head and neck squamous cell carcinoma, cholangiocarcinoma, and
      bladder cancer. Although several FGFR kinase inhibitors have entered clinical
      trials, single-agent clinical efficacy has been modest and resistance invariably
      occurs. We therefore conducted a genome-wide functional screen to characterize
      mechanisms of resistance to FGFR inhibition in a FGFR1-dependent lung cancer
      cellular model. Our screen identified known resistance drivers, such as MET, and
      additional novel resistance mediators including members of the neurotrophin
      receptor pathway (NTRK), the TAM family of tyrosine kinases (TYRO3, MERTK, AXL),
      and MAPK pathway, which were further validated in additional FGFR-dependent
      models. In an orthogonal approach, we generated a large panel of resistant clones
      by chronic exposure to FGFR inhibitors in FGFR1- and FGFR3-dependent cellular
      models and characterized gene expression profiles employing the L1000 platform.
      Notably, resistant clones had enrichment for NTRK and MAPK signaling pathways.
      Novel mediators of resistance to FGFR inhibition were found to compensate for
      FGFR loss in part through reactivation of MAPK pathway. Intriguingly,
      coinhibition of FGFR and specific receptor tyrosine kinases identified in our
      screen was not sufficient to suppress ERK activity or to prevent resistance to
      FGFR inhibition, suggesting a redundant reactivation of RAS-MAPK pathway. Dual
      blockade of FGFR and MEK, however, proved to be a more powerful approach in
      preventing resistance across diverse FGFR dependencies and may represent a
      therapeutic opportunity to achieve durable responses to FGFR inhibition in FGFR
      dependent cancers. Mol Cancer Ther; 17(7); 1526-39. (c)2018 AACR.

PMID- 29654071
TI  - Evolution of an allosteric "off switch" in apoptotic caspases.
AB  - Caspase-3 is well known as the "executioner" whose activation commits the cell to
      an apoptotic fate, but low levels of caspase-3 activity also play key roles in
      development. A new study explains how cells can balance these functions, using
      biophysical, structural, and computational approaches to demonstrate the
      mechanism by which phosphorylation of conserved sites on a distal surface loop
      reduces or abolishes catalytic activity. These results provide new insights into
      allosteric regulation mechanisms and offer new opportunities for development of
      caspase-3 modulators.

PMID- 29654070
TI  - A novel k-mer set memory (KSM) motif representation improves regulatory variant
      prediction.
AB  - The representation and discovery of transcription factor (TF) sequence binding
      specificities is critical for understanding gene regulatory networks and
      interpreting the impact of disease-associated noncoding genetic variants. We
      present a novel TF binding motif representation, the k-mer set memory (KSM),
      which consists of a set of aligned k-mers that are overrepresented at TF binding
      sites, and a new method called KMAC for de novo discovery of KSMs. We find that
      KSMs more accurately predict in vivo binding sites than position weight matrix
      (PWM) models and other more complex motif models across a large set of ChIP-seq
      experiments. Furthermore, KSMs outperform PWMs and more complex motif models in
      predicting in vitro binding sites. KMAC also identifies correct motifs in more
      experiments than five state-of-the-art motif discovery methods. In addition, KSM
      derived features outperform both PWM and deep learning model derived sequence
      features in predicting differential regulatory activities of expression
      quantitative trait loci (eQTL) alleles. Finally, we have applied KMAC to 1600
      ENCODE TF ChIP-seq data sets and created a public resource of KSM and PWM motifs.
      We expect that the KSM representation and KMAC method will be valuable in
      characterizing TF binding specificities and in interpreting the effects of
      noncoding genetic variations.

PMID- 29654072
TI  - Sex steroid hormones as neuroprotective elements in ischemia models.
AB  - Among sex steroid hormones, progesterone and estradiol have a wide diversity of
      physiological activities that target the nervous system. Not only are they
      carried by the blood stream, but also they are locally synthesized in the brain
      and for this reason, estradiol and progesterone are considered 'neurosteroids'.
      The physiological actions of both hormones range from brain development and
      neurotransmission to aging, illustrating the importance of a deep understanding
      of their mechanisms of action. In this review, we summarize key roles that
      estradiol and progesterone play in the brain. As numerous reports have confirmed
      a substantial neuroprotective role for estradiol in models of neurodegenerative
      disease, we focus this review on traumatic brain injury and stroke models. We
      describe updated data from receptor and signaling events triggered by both
      hormones, with an emphasis on the mechanisms that have been reported as 'rapid'
      or 'cytoplasmic actions'. Data showing the therapeutic effects of the hormones,
      used alone or in combination, are also summarized, with a focus on rodent models
      of middle cerebral artery occlusion (MCAO). Finally, we draw attention to
      evidence that neuroprotection by both hormones might be due to a combination of
      'cytoplasmic' and 'nuclear' signaling.

PMID- 29654073
TI  - Next on your 'to do' list Mr Gove ....

PMID- 29654074
TI  - Recruitment crisis demands a solution NOW!

PMID- 29654075
TI  - New licensing regulations are an opportunity to combat harmful breeding in dogs,
      say vets.

PMID- 29654076
TI  - Vets must report suspicions of illegal imports.

PMID- 29654077
TI  - Campaign to tackle puppy trade in Scotland.

PMID- 29654079
TI  - Call for evidence on live exports launched.

PMID- 29654080
TI  - Celebrating veterinary achievements.

PMID- 29654083
TI  - Staphylococcal pyoderma: challenges and therapeutic considerations.

PMID- 29654085
TI  - Large corporate acquisitions and the shortage of vets.

PMID- 29654086
TI  - Good vets are voting with their feet.

PMID- 29654087
TI  - Are we asking enough questions?

PMID- 29654088
TI  - Correction: Practical guide to small animal theatre practice.

PMID- 29654090
TI  - Re-emergence of canine distemper in wildlife in Belgium.

PMID- 29654091
TI  - Caring for a dog with osteoarthritis.
AB  - An owner describes how life changed when her dog was diagnosed with
      osteoarthritis.

PMID- 29654094
TI  - Exercise testing in patients with asymptomatic moderate or severe aortic
      stenosis.
AB  - OBJECTIVE: To assess the safety and tolerability of treadmill exercise testing
      and the association of revealed symptoms with outcome in apparently asymptomatic
      patients with moderate to severe aortic stenosis (AS). METHODS: A retrospective
      cohort study of 316 patients (age 65+/-12 years, 67% men) with moderate and
      severe AS who underwent echocardiography and modified Bruce exercise treadmill
      tests (ETTs) at a specialist valve clinic. The outcome measures were aortic valve
      replacement (AVR), all-cause mortality or a composite of AVR and all-cause
      mortality. RESULTS: At baseline, there were 210 (66%) patients with moderate and
      106 (34%) with severe AS. There were 264 (83%) events. 234 (74%) patients reached
      an indication for AVR, 145 (69%) with moderate and 88 (83%) with severe AS
      (p<0.05). Of the 30 (9%) deaths recoded during follow-up, 20 (67%) were
      cardiovascular related. In total, 797 exercise tests (mean 2.5+/-2.1 per patient)
      were performed. No serious adverse events were observed. The prevalence of
      revealed symptoms at baseline ETT was 29% (n=91) and was significantly higher in
      severe AS compared with moderate AS (38%vs23%, p=0.008). Symptoms were revealed
      in 18%-59% of patients during serial ETT conducted over a follow-up period of
      34.9 (SD 35.1) months. The event-free survival at 24 months with revealed
      symptoms was 46%+/-4% and without revealed symptoms was 70%+/-4%. CONCLUSIONS:
      ETT in patients with moderate or severe AS is safe and tolerable. Serial exercise
      testing is useful to reveal symptoms not volunteered on the history and adds
      incremental prognostic information to baseline testing.

PMID- 29654095
TI  - Cardiac rehabilitation and physical activity: systematic review and meta
      analysis.
AB  - OBJECTIVE: To undertake a systematic review and meta-analysis to assess the
      impact of cardiac rehabilitation (CR) on physical activity (PA) levels of
      patients with heart disease and the methodological quality of these studies.
      METHODS: Databases (MEDLINE, EMBASE, CENTRAL, CINAHL, PsychINFO and SportDiscus)
      were searched without language restriction from inception to January 2017 for
      randomised controlled trials (RCTs) comparing CR to usual care control in adults
      with heart failure (HF) or coronary heart disease (CHD) and measuring PA
      subjectively or objectively. The direction of PA difference between CR and
      control was summarised using vote counting (ie, counting the positive, negative
      and non-significant results) and meta-analysis. RESULTS: Forty RCTs, (6480
      patients: 5825 CHD, 655 HF) were included with 26% (38/145) PA results showing a
      statistically significant improvement in PA levels with CR compared with control.
      This pattern of results appeared consistent regardless of type of CR intervention
      (comprehensive vs exercise-only) or PA measurement (objective vs subjective).
      Meta-analysis showed PA increases in the metrics of steps/day (1423, 95% CI
      757.07 to 2089.43, p<0.0001) and proportion of patients categorised as physically
      active (relative risk 1.55, 95% CI 1.19 to 2.02, p=0.001). The included trials
      were at high risk of bias, and the quality of the PA assessment and reporting was
      relatively poor. CONCLUSION: Overall, there is moderate evidence of an increase
      in PA with CR participation compared with control. High-quality trials are
      required, with robust PA measurement and data analysis methods, to assess if CR
      definitely leads to important improvements in PA.

PMID- 29654096
TI  - Cost-effectiveness of cardiac rehabilitation: a systematic review.
AB  - Patients may be offered cardiac rehabilitation (CR), a supervised programme often
      including exercises, education and psychological care, following a cardiac event,
      with the aim of reducing morbidity and mortality. Cost-constrained healthcare
      systems require information about the best use of budget and resources to
      maximise patient benefit. We aimed to systematically review and critically
      appraise economic studies of CR and its components. In January 2016, validated
      electronic searches of the National Health Service Economic Evaluation Database
      (NHS EED), Health Technology Assessment, PsycINFO, MEDLINE and Embase databases
      were run to identify full economic evaluations published since 2001. Two levels
      of screening were used and explicit inclusion criteria were applied. Prespecified
      data extraction and critical appraisal were performed using the NHS EED handbook
      and Drummond checklist. The majority of studies concluded that CR was cost
      effective versus no CR (incremental cost-effectiveness ratios (ICERs) ranged from
      $1065 to $71 755 per quality-adjusted life-year (QALY)). Evidence for specific
      interventions within CR was varied; psychological intervention ranged from
      dominant (cost saving and more effective) to $226 128 per QALY, telehealth ranged
      from dominant to $588 734 per QALY and while exercise was cost-effective across
      all relevant studies, results were subject to uncertainty. Key drivers of cost
      effectiveness were risk of subsequent events and hospitalisation, hospitalisation
      and intervention costs, and utilities. This systematic review of studies
      evaluates the cost-effectiveness of CR in the modern era, providing a fresh
      evidence base for policy-makers. Evidence suggests that CR is cost-effective,
      especially with exercise as a component. However, research is needed to determine
      the most cost-effective design of CR.

PMID- 29654097
TI  - 56-year-old lady with transaortic gradient.
AB  - CLINICAL INTRODUCTION: A 56-year-old lady with a background of hypertension was
      admitted to our institution with acute pulmonary oedema. She reported gradual and
      increasingly severe dyspnoea on exertion over the preceding 12 months and, prior
      to presentation, her exercise tolerance was restricted to one flight of stairs.
      On transthoracic echocardiography during the index admission, left ventricular
      size and systolic function were normal, and peak and mean transaortic gradients
      were 67 mm Hg and 33 mm Hg, respectively, with a peak velocity of 3.9 m/s. No
      aortic incompetence or other significant valvular abnormality was noted. A
      transoesophageal echocardiogram was performed. Figure 1 depicts the mid
      oesophageal parasternal long-axis view. What is the explanation behind the
      significant transaortic gradient?heartjnl;104/12/1036/F1F1F1Figure
      1Transoesophageal echocardiogram, mid-oesophageal long-axis view at 135 degrees.
      QUESTION: What is the explanation behind the significant transaortic
      gradient?Ventricular septal defect Supravalvular aortic stenosisAortic valvular
      stenosisSubaortic membraneHypertrophic obstructive cardiomyopathy.

PMID- 29654099
TI  - Liver Failure in Advanced Adult-onset Polycystic Kidney Disease.
AB  - Polycystic liver disease is the most common extrarenal manifestation of autosomal
      dominant polycystic kidney disease (ADPKD). Hepatic cysts are typically
      incidental findings, with occasional complications including cyst haemorrhage,
      infection and rupture. In contrast to the typically benign course of polycystic
      liver disease, we present a rare case of fatal decompensated liver failure in a
      patient with ADPKD. This is a case of a 58-year-old man with end-stage renal
      disease on haemodialysis presenting with new-onset ascites and decompensated
      liver failure following bilateral nephrectomy. Cirrhosis in ADPKD is a late
      manifestation of the disease, but it should be considered in the perioperative
      risk of patients with ADPKD.

PMID- 29654100
TI  - Malignant rhabdoid tumour of the neck in a neonate.
AB  - Fetal neck masses are rare, and present a challenge antenatally, during delivery
      and in making a diagnosis. In this report, we detail the presentation of a
      neonate with a neck mass diagnosed in the third trimester. The baby was delivered
      by ex utero intrapartum therapy (EXIT). Investigations sent included an MRI with
      limited CT cuts, and a biopsy, which lead to the diagnosis of a malignant
      rhabdoid tumour. This is rare and the overall survival is low.

PMID- 29654098
TI  - Functional Assays to Screen and Dissect Genomic Hits: Doubling Down on the
      National Investment in Genomic Research.
AB  - The National Institutes of Health have made substantial investments in genomic
      studies and technologies to identify DNA sequence variants associated with human
      disease phenotypes. The National Heart, Lung, and Blood Institute has been at the
      forefront of these commitments to ascertain genetic variation associated with
      heart, lung, blood, and sleep diseases and related clinical traits. Genome-wide
      association studies, exome- and genome-sequencing studies, and exome-genotyping
      studies of the National Heart, Lung, and Blood Institute-funded epidemiological
      and clinical case-control studies are identifying large numbers of genetic
      variants associated with heart, lung, blood, and sleep phenotypes. However,
      investigators face challenges in identification of genomic variants that are
      functionally disruptive among the myriad of computationally implicated variants.
      Studies to define mechanisms of genetic disruption encoded by computationally
      identified genomic variants require reproducible, adaptable, and inexpensive
      methods to screen candidate variant and gene function. High-throughput strategies
      will permit a tiered variant discovery and genetic mechanism approach that begins
      with rapid functional screening of a large number of computationally implicated
      variants and genes for discovery of those that merit mechanistic investigation.
      As such, improved variant-to-gene and gene-to-function screens-and adequate
      support for such studies-are critical to accelerating the translation of genomic
      findings. In this White Paper, we outline the variety of novel technologies,
      assays, and model systems that are making such screens faster, cheaper, and more
      accurate, referencing published work and ongoing work supported by the National
      Heart, Lung, and Blood Institute's R21/R33 Functional Assays to Screen Genomic
      Hits program. We discuss priorities that can accelerate the impressive but
      incomplete progress represented by big data genomic research.

PMID- 29654101
TI  - Anti-TNF therapy-induced lupus erythematosus-like syndrome in a patient treated
      with adalimumab for cutaneous psoriasis.
AB  - A 44-year-old woman with cutaneous psoriasis and no history of joint involvement
      recently treated with adalimumab was admitted to the inpatient Internal Medicine
      service for uncontrolled, severe joint pain so debilitating that it limited her
      activities of daily living and prevented her from working as a medical
      technologist. She had stopped taking adalimumab 3 weeks prior to presentation
      after receiving approximately 2.5 months of therapy for cutaneous psoriasis
      unresponsive to trials of topical steroids and methotrexate. Antinuclear antibody
      and anti-double-stranded DNA antibodies were positive at high titres. She
      received a course of oral corticosteroids with improvement in her symptoms.

PMID- 29654102
TI  - Orbital cystic schwannoma masquerading as hydatid cyst.
AB  - Gradually increasing abaxial proptosis in a middle-aged female patient revealed a
      large well-defined cystic lesion behind the globe extending till the orbital
      apex. B scan ultrasound and CT findings were favouring a diagnosis of orbital
      hydatid cyst. Thus as a diagnostic/curative surgical protocol, the cystic lesion
      was removed in total. However, intraoperative gross specimen examination was not
      classical of hydatid cyst, thus a further histopathological evaluation was
      carried out, which confirmed the diagnosis of orbital schwannoma with extensive
      cystic degeneration. Postoperatively the clinical course was uneventful at the
      end of 1 year.

PMID- 29654103
TI  - Embryonal rhabdomyosarcoma of urinary bladder in an adult patient: an unusual
      manifestation.
AB  - An adult man presented with off and on painless haematuria, which was diagnosed
      as bladder mass on contrast-enhanced CT. He underwent transurethral resection of
      bladder tumour with complete resection. A diagnosis of embryonal rhabdomyosarcoma
      was made following histopathology and immunohistochemistry report. The patient
      was planned for radical cystectomy but was found to have large recurrent
      infiltrating bladder mass with liver and bone metastasis. Hence, the plan for
      radical cystectomy was deferred and the patient was counselled regarding
      chemotherapy (vincristine, cisplatin and doxorubicin regime). The patient
      tolerated the first cycle of chemotherapy, but his condition deteriorated prior
      to the second cycle and the patient expired.

PMID- 29654104
TI  - Ruptured choledochal cyst during early pregnancy with successful fetomaternal
      outcome.
AB  - Choledochal cyst is a rare congenital malformation which is usually found in
      young children and adolescents but can rarely present in the adult age group. It
      can present with several complications like cholangitis, pancreatitis, biliary
      cirrhosis, portal hypertension, liver abscess, malignancy and rarely spontaneous
      rupture (in 2% of cases) causing biliary peritonitis. A case of spontaneous
      rupture of choledochal cyst during second trimester of pregnancy is reported
      where the patient was managed by minimal surgery, peritoneal washout, placement
      of T-tube and planned for definitive treatment in the postpartum period. The
      pregnancy continued till 35 weeks with favourable fetomaternal outcome.

PMID- 29654105
TI  - Acute acalculous cholecystitis of an intrahepatic gallbladder causing Mirizzi's
      syndrome.
AB  - We present the case of a young female with symptoms of biliary colic and a
      biochemical profile consistent with biliary obstruction. Imaging was suspicious
      for Mirizzi's syndrome. Intraoperatively, the patient was found to have a
      complete intrahepatic gallbladder causing common hepatic duct compression with
      final pathology confirming acute cholecystitis. We review the embryological
      development of the gallbladder as well as clinical presentation of Mirizzi's
      syndrome. Special consideration for clinical workup and surgical management is
      discussed.

PMID- 29654106
TI  - Meningitis due to scrub typhus: the importance of a differential diagnosis in an
      endemic area.
AB  - A patient with fever and neck stiffness was treated as partially treated
      bacterial meningitis based on history, examination and cerebrospinal fluid
      analysis. After initial improvement with ceftriaxone, vancomycin and
      dexamethasone, symptoms recurred. Fever resolved promptly after treatment was
      started with doxycycline, when scrub typhus immunoglobulin M test came positive.
      Meningitis is a well-known complication of scrub typhus. However, scrub typhus is
      seldom considered in the differential diagnosis of meningitis in the Indian
      subcontinent. Early diagnosis and prompt institution of doxycycline therapy may
      lead to early cure of scrub typhus even when features of meningitis supervene.
      However, ceftriaxone which is commonly used to treat bacterial meningitis is
      suboptimal in the treatmenwgt36t of scrub typhus.

PMID- 29654107
TI  - Infertility: an out-of-the-box cause of postmenopausal endometrial thickening.

PMID- 29654108
TI  - Misguided urinary catheter: an uncommon complication of a common solution.

PMID- 29654109
TI  - Nucleic acid-induced potentiation of matrix metalloproteinase-9 enzymatic
      activity.
AB  - Matrix metalloproteinases (MMPs) play varied roles in normal biology and diseases
      where, depending on the context, both inhibition and enhancement of the enzymatic
      activity may be beneficial. However, there are very few reports of positive
      modulators of MMP activity. We report that polynucleotides, including single
      stranded DNA, RNA, and even double-stranded DNA, bind to and enhance the
      enzymatic activity of MMP9. This enhancement of MMP9 catalytic activity is not
      shared by biologically active polycationic molecules suggesting nonspecific
      charge screening as an unlikely mechanism. Deletion construct and MMP1, 2, and 3
      studies suggest that the type-II fibronectin repeat domains of the enzyme appear
      to play a role in mediating the nucleotide potentiation of MMP9 activity. Single
      stranded DNA enhances nerve growth factor-induced MMP9-dependent neurite
      extension in pheochromocytoma 12 cells providing evidence for potential
      biological significance of the nucleotide-mediated allosteric enhancement of the
      catalytic activity.

PMID- 29654110
TI  - Deregulation of LIMD1-VHL-HIF-1alpha-VEGF pathway is associated with different
      stages of cervical cancer.
AB  - To understand the mechanism of cellular stress in basal-parabasal layers of
      normal cervical epithelium and during different stages of cervical carcinoma, we
      analyzed the alterations (expression/methylation/copy number variation/mutation)
      of HIF-1alpha and its associated genes LIMD1, VHL and VEGF in disease-free normal
      cervix (n = 9), adjacent normal cervix of tumors (n = 70), cervical
      intraepithelial neoplasia (CIN; n = 32), cancer of uterine cervix (CACX; n = 174)
      samples and two CACX cell lines. In basal-parabasal layers of normal cervical
      epithelium, LIMD1 showed high protein expression, while low protein expression of
      VHL was concordant with high expression of HIF-1alpha and VEGF irrespective of
      HPV-16 (human papillomavirus 16) infection. This was in concordance with the low
      promoter methylation of LIMD1 and high in VHL in the basal-parabasal layers of
      normal cervix. LIMD1 expression was significantly reduced while VHL expression
      was unchanged during different stages of cervical carcinoma. This was in
      concordance with their frequent methylation during different stages of this
      tumor. In different stages of cervical carcinoma, the expression pattern of HIF
      1alpha and VEGF was high as seen in basal-parabasal layers and inversely
      correlated with the expression of LIMD1 and VHL. This was validated by
      demethylation experiments using 5-aza-2'-deoxycytidine in CACX cell lines.
      Additional deletion of LIMD1 and VHL in CIN/CACX provided an additional growth
      advantage during cervical carcinogenesis through reduced expression of genes and
      associated with poor prognosis of patients. Our data showed that overexpression
      of HIF-1alpha and its target gene VEGF in the basal-parabasal layers of normal
      cervix was due to frequent inactivation of VHL by its promoter methylation. This
      profile was maintained during different stages of cervical carcinoma with
      additional methylation/deletion of VHL and LIMD1.

PMID- 29654111
TI  - High prevalence of electrocardiac abnormalities in anti-CASPR2 antibody
      associated disease.

PMID- 29654112
TI  - Long-term effect of low frequency stimulation of STN on dysphagia, freezing of
      gait and other motor symptoms in PD.
AB  - OBJECTIVE: To evaluate the long-term effect of 60 Hz stimulation of the
      subthalamic nucleus (STN) on dysphagia, freezing of gait (FOG) and other motor
      symptoms in patients with Parkinson's disease (PD) who have FOG at the usual 130
      Hz stimulation. METHODS: This is a prospective, sequence randomised, crossover,
      double-blind study. PD patients with medication refractory FOG at 130 Hz
      stimulation of the STN were randomised to the sequences of 130 Hz, 60 Hz or deep
      brain stimulation off to assess swallowing function (videofluoroscopic evaluation
      and swallowing questionnaire), FOG severity (stand-walk-sit test and FOG
      questionnaire) and motor function (Unified PD Rating Scale, Part III motor
      examination (UPDRS-III)) at initial visit (V1) and follow-up visit (V2, after
      being on 60 Hz stimulation for an average of 14.5 months), in their usual
      medications on state. The frequency of aspiration events, perceived swallowing
      difficulty and FOG severity at 60 Hz compared with 130 Hz stimulation at V2, and
      their corresponding changes at V2 compared with V1 at 60 Hz were set as primary
      outcomes, with similar comparisons in UPDRS-III and its subscores as secondary
      outcomes. RESULTS: All 11 enrolled participants completed V1 and 10 completed V2.
      We found the benefits of 60 Hz stimulation compared with 130 Hz in reducing
      aspiration frequency, perceived swallowing difficulty, FOG severity, bradykinesia
      and overall axial and motor symptoms at V1 and persistent benefits on all of them
      except dysphagia at V2, with overall decreasing efficacy when comparing V2 to V1.
      CONCLUSIONS: The 60 Hz stimulation, when compared with 130 Hz, has long-term
      benefits on reducing FOG, bradykinesia and overall axial and motor symptoms
      except dysphagia, although the overall benefits decrease with long-term use.
      CLINICAL TRIAL REGISTRATION: NCT02549859; Pre-results.

PMID- 29654113
TI  - Effect of phacoemulsification on facility of outflow.
AB  - PURPOSE: Phacoemulsification has been shown to reduce intraocular pressure (IOP).
      The mechanism of action is thought to be via increased trabecular outflow
      facility. However, studies on the relationship between phacoemulsification and
      outflow facility have been inconsistent. This study intended to examine the
      change in electronic Schiotz tonographic outflow facility (TOF) and IOP
      measurements following phacoemulsification. METHODS: Patients who were due to
      undergo a standard clear corneal incision phacoemulsification with intraocular
      lens (IOL) implantation, at St Thomas' Hospital, were invited to participate in
      this study. IOP was measured using Goldmann's applanation tonometer, and TOF was
      measured by electronic Schiotz tonography at baseline and at 3, 6 and 12 months
      postoperatively. RESULTS: Forty-one patients were recruited. Tonography data for
      27 patients were reliable and available at all time points. Eleven cases had
      primary open angle glaucoma and cataract, while 16 patients had cataract only.
      Mean IOP reduced at every time point postoperatively significantly compared with
      baseline. TOF improved significantly after cataract extraction at all time points
      (baseline of 0.14+/-0.06 vs 0.18+/-0.09 at 3 months, P=0.02 and 0.20+/-0.09 at 6
      months, P=0.003, 0.17+/-0.07 uL/min mmHg at 12 months, P=0.04). Five
      contralateral eyes of patients with cataracts only who did not have any
      intraocular surgery during the follow-up period were used as comparison. Their
      IOP and TOF did not change significantly at any postoperative visits. CONCLUSION:
      This is the first study using electronic Schiotz tonography with documented
      anterior chamber depth and gonioscopy after modern cataract surgery (CS) with
      phacoemulsification and IOL implantation. We demonstrated that
      phacoemulsification increases TOF and this fully accounts for the IOP reduction
      following CS. ISTCRN REGISTRATION NUMBER: ISRCTN04247738.

PMID- 29654114
TI  - Multimodal imaging approach to monitor browning of adipose tissue in vivo.
AB  - The discovery that white adipocytes can undergo a browning process to become
      metabolically active beige cells has attracted significant interest in the fight
      against obesity. However, the study of adipose browning has been impeded by a
      lack of imaging tools that allow longitudinal and noninvasive monitoring of this
      process in vivo. Here, we report a preclinical imaging approach to detect
      development of beige adipocytes during adrenergic stimulation. In this approach,
      we expressed near-infrared fluorescent protein, iRFP720, driven under an
      uncoupling protein-1 (Ucp1) promoter in mice by viral transduction, and used
      multispectral optoacoustic imaging technology with ultrasound tomography (MSOT
      US) to assess adipose beiging during adrenergic stimulation. We observed
      increased photoacoustic signal at 720 nm, coupled with attenuated lipid signals
      in stimulated animals. As a proof of concept, we validated our approach against
      hybrid positron emission tomography combined with magnetic resonance (PET/MR)
      imaging modality, and quantified the extent of adipose browning by MRI-guided
      segmentation of 2-deoxy-2-18F-fluoro-d-glucose uptake signals. The browning
      extent detected by MSOT-US and PET/MR are well correlated with Ucp1 induction.
      Taken together, these systems offer great opportunities for preclinical screening
      aimed at identifying compounds that promote adipose browning and translation of
      these discoveries into clinical studies of humans.

PMID- 29654115
TI  - Nonmuscle myosin IIA is involved in recruitment of apical junction components
      through activation of alpha-catenin.
AB  - MDCK dog kidney epithelial cells express two isoforms of nonmuscle myosin heavy
      chain II, IIA and IIB. Using the CRISPR/Cas9 system, we established cells in
      which the IIA gene was ablated. These cells were then transfected with a vector
      that expresses GFP-IIA chimeric molecule under the control of a tetracycline
      responsible element. In the absence of Dox (doxycyclin), when GFP-IIA is
      expressed (GFP-IIA+), the cells exhibit epithelial cell morphology, but in the
      presence of Dox, when expression of GFP-IIA is repressed (GFP-IIA-), the cells
      lose epithelial morphology and strong cell-cell adhesion. Consistent with these
      observations, GFP-IIA- cells failed to assemble junction components such as E
      cadherin, desmoplakin, and occludin at cell-cell contact sites. Therefore, IIA is
      required for assembly of junction complexes. MDCK cells with an ablation of the
      alpha-catenin gene also exhibited the same phenotype. However, when in GFP-IIA-
      cells expressed alpha-catenin lacking the inhibitory region or E-cadherin/alpha
      catenin chimeras, the cells acquired the ability to establish the junction
      complex. These experiments reveal that IIA acts as an activator of alpha-catenin
      in junction assembly.

PMID- 29654117
TI  - Correction: 'Microbes in sport' -The potential role of the gut microbiota in
      athlete health and performance.

PMID- 29654119
TI  - The OCT-ORION Study: A Randomized Optical Coherence Tomography Study Comparing
      Resolute Integrity to Biomatrix Drug-Eluting Stent on the Degree of Early Stent
      Healing and Late Lumen Loss.
AB  - BACKGROUND: Durable polymers used in drug-eluting stents are considered a
      potential cause of hypersensitivity inflammatory response adversely affecting
      stent healing. Using a sequential follow-up with optical coherence tomography, we
      compared the differences in healing profiles of 2 drug-eluting stents with a
      biodegradable or durable polymer. METHODS AND RESULTS: Sixty patients with
      multivessel disease were prospectively enrolled to receive both study stents,
      which were randomly assigned to 2 individual vessels, a Resolute Integrity
      zotarolimus-eluting stent with a durable BioLinx polymer and a BioMatrix NeoFlex
      Biolimus A9-eluting stent with a biodegradable polylactic acid polymer. Optical
      coherence tomography was performed at baseline, then in 5 randomly assigned
      monthly groups at 2 to 6 months, and at 9 months in all patients. The primary end
      point was the difference in optical coherence tomography strut coverage at 9
      months. Key secondary end points included angiographic late lumen loss and
      composite major adverse cardiac events (cardiac death, myocardial infarction,
      target lesion revascularization, and definite or probable stent thrombosis) at 9
      months. Resolute Integrity zotarolimus-eluting stent showed significantly better
      strut coverage than BioMatrix NeoFlex Biolimus A9-eluting stent at 2 to 6 months
      (P<0.001) and less variance of percent coverage at 9 months, 99.7% (interquartile
      range, 99.1-100) versus 99.6% (interquartile range, 96.8-99.9; difference, 0.10;
      95% confidence interval, 0.00-1.05; P<0.001). No significant difference was
      observed in major adverse cardiac events or angiographic end points. CONCLUSIONS:
      Despite having a durable polymer, Resolute Integrity zotarolimus-eluting stent
      exhibited better strut coverage than BioMatrix NeoFlex Biolimus A9-eluting stent
      having a biodegradable polymer; both showed similar antiproliferative efficacy.
      This novel, longitudinal, sequential optical coherence tomography protocol using
      each patient as own control could achieve conclusive results in small sample
      size. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique
      identifier: NCT01742507.

PMID- 29654116
TI  - Robust interaction of IFT70 with IFT52-IFT88 in the IFT-B complex is required for
      ciliogenesis.
AB  - In the intraflagellar transport (IFT) machinery, the IFT-B and IFT-A complexes
      mediate anterograde and retrograde ciliary protein trafficking, respectively.
      Among the 16 subunits of the IFT-B complex, several subunits are essential for
      ciliogenesis, whereas others, which are associated peripherally with the complex,
      are dispensable for ciliogenesis but play a role in protein trafficking. IFT22
      knockout (KO) cells established in this study demonstrated no defects in
      ciliogenesis or ciliary protein trafficking. In stark contrast, IFT70A and IFT70B
      double-knockout cells did not form cilia, even though IFT70 is associated
      peripherally with the IFT-B complex via the IFT52-IFT88 dimer, and other IFT-B
      subunits assembled at the ciliary base in the absence of IFT70. Exogenous
      expression of either IFT70A or IFT70B restored the ciliogenesis defect of IFT70
      KO cells, indicating their redundant roles. IFT70 has 15 consecutive
      tetratricopeptide repeats (TPRs) followed by a short helix (alpha36). Deletion of
      the first TPR or alpha36 of IFT70A greatly reduced its ability to interact with
      the IFT52-IFT88 dimer. Exogenous expression of any of the IFT70A deletion mutants
      in IFT70-KO cells could not restore ciliogenesis. These results show that IFT70
      plays an essential role in ciliogenesis, although it is dispensable for assembly
      of the residual IFT-B subunits.

PMID- 29654120
TI  - Interventional Cardiology: The In and the Out.

PMID- 29654121
TI  - On the popularity of the USB flash drive-shaped electronic cigarette Juul.

PMID- 29654122
TI  - Cigarette pack messages about toxic chemicals: a randomised clinical trial.
AB  - BACKGROUND: The USA can require tobacco companies to disclose information about
      harmful and potentially harmful chemicals in cigarette smoke, but the impact of
      these messages is uncertain. We sought to assess the effect of placing messages
      about toxic chemicals on smokers' cigarette packs. METHODS: Participants were 719
      adult cigarette smokers from California, USA, recruited from September 2016
      through March 2017. We randomly assigned smokers to receive either factual
      messages about chemicals in cigarette smoke and their health harms (intervention)
      or messages about not littering cigarette butts (control) on the side of their
      cigarette packs for 3 weeks. The primary trial outcome was intention to quit
      smoking. RESULTS: In intent-to-treat analyses, smokers whose packs had chemical
      messages did not have higher intentions to quit smoking at the end of the trial
      than those whose packs had control messages (P=0.56). Compared with control
      messages, chemical messages led to higher awareness of the chemicals (28% vs 15%,
      P<0.001) and health harms (60% vs 52%, P=0.02) featured in the messages. In
      addition, chemical messages led to greater negative affect, thinking about the
      chemicals in cigarettes and the harms of smoking, conversations about the
      messages and forgoing a cigarette (all P<0.05). DISCUSSION: Chemical messages on
      cigarette packs did not lead to higher intentions to quit among smokers in our
      trial. However, chemical messages informed smokers of chemicals in cigarettes and
      harms of smoking, which directly supports their implementation and would be
      critical to defending the messages against cigarette company legal challenges.
      TRIAL REGISTRATION NUMBER: NCT02785484.

PMID- 29654123
TI  - Who is the target? Package health warnings and the role of market segmentation.

PMID- 29654125
TI  - Electrical Substrates Driving Response to Cardiac Resynchronization Therapy: A
      Combined Clinical-Computational Evaluation.
AB  - BACKGROUND: The predictive value of interventricular versus intraventricular
      dyssynchrony for response to cardiac resynchronization therapy (CRT) remains
      unclear. We investigated the relative importance of both ventricular electrical
      substrate components for left ventricular (LV) hemodynamic function. METHODS AND
      RESULTS: First, we used the cardiovascular computational model CircAdapt to
      characterize the isolated effect of intrinsic interventricular and
      intraventricular activation on CRT response (DeltaLVdP/dtmax). Simulated
      DeltaLVdP/dtmax (range: 1.3%-26.5%) increased considerably with increasing
      interventricular dyssynchrony. In contrast, the isolated effect of
      intraventricular dyssynchrony in either the LV or right ventricle was limited
      (DeltaLVdP/dtmax range: 12.3%-18.3% and 14.1%-15.7%, respectively). Effects of
      activation during biventricular pacing on DeltaLVdP/dtmax were small. Second,
      electrocardiographic imaging-derived activation characteristics of 51 CRT
      candidates were used to personalize ventricular activation in CircAdapt. The
      individualized models were subsequently used to assess the accuracy of
      DeltaLVdP/dtmax prediction based on the electrical data. The model-predicted
      DeltaLVdP/dtmax was close to the actual value in patients with left bundle branch
      block (measured-simulated: 2.7+/-9.0%) when only intrinsic interventricular
      dyssynchrony was personalized. Among patients without left bundle branch block,
      DeltaLVdP/dtmax was systematically overpredicted by CircAdapt (measured
      simulated: 9.2+/-7.1%). Adding intraventricular activation to the model did not
      improve the accuracy of the response prediction. CONCLUSIONS: Computer
      simulations revealed that intrinsic interventricular dyssynchrony is the dominant
      component of the electrical substrate driving the response to CRT. Intrinsic
      intraventricular dyssynchrony and any dyssynchrony during biventricular pacing
      play a minor role in this respect. This may facilitate patient-specific modeling
      for prediction of CRT response. CLINICAL TRIAL REGISTRATION: URL:
      https://www.clinicaltrials.gov. Unique identifier: NCT01270646.

PMID- 29654124
TI  - Genomic Instability Promoted by Overexpression of Mismatch Repair Factors in
      Yeast: A Model for Understanding Cancer Progression.
AB  - Mismatch repair (MMR) proteins act in spellchecker roles to excise
      misincorporation errors that occur during DNA replication. Curiously, large-scale
      analyses of a variety of cancers showed that increased expression of MMR proteins
      often correlated with tumor aggressiveness, metastasis, and early recurrence. To
      better understand these observations, we used The Cancer Genome Atlas and Gene
      Expression across Normal and Tumor tissue databases to analyze MMR protein
      expression in cancers. We found that the MMR genes MSH2 and MSH6 are
      overexpressed more frequently than MSH3, and that MSH2 and MSH6 are often
      cooverexpressed as a result of copy number amplifications of these genes. These
      observations encouraged us to test the effects of upregulating MMR protein levels
      in baker's yeast, where we can sensitively monitor genome instability phenotypes
      associated with cancer initiation and progression. Msh6 overexpression (two- to
      fourfold) almost completely disrupted mechanisms that prevent recombination
      between divergent DNA sequences by interacting with the DNA polymerase
      processivity clamp PCNA and by sequestering the Sgs1 helicase. Importantly,
      cooverexpression of Msh2 and Msh6 (~eightfold) conferred, in a PCNA interaction
      dependent manner, several genome instability phenotypes including increased
      mutation rate, increased sensitivity to the DNA replication inhibitor HU and the
      DNA-damaging agents MMS and 4-nitroquinoline N-oxide, and elevated loss-of
      heterozygosity. Msh2 and Msh6 cooverexpression also altered the cell cycle
      distribution of exponentially growing cells, resulting in an increased fraction
      of unbudded cells, consistent with a larger percentage of cells in G1. These
      novel observations suggested that overexpression of MSH factors affected the
      integrity of the DNA replication fork, causing genome instability phenotypes that
      could be important for promoting cancer progression.

PMID- 29654126
TI  - Oxidized CaMKII (Ca2+/Calmodulin-Dependent Protein Kinase II) Is Essential for
      Ventricular Arrhythmia in a Mouse Model of Duchenne Muscular Dystrophy.
AB  - BACKGROUND: Duchenne muscular dystrophy patients are prone to ventricular
      arrhythmias, which may be caused by abnormal calcium (Ca2+) homeostasis and
      elevated reactive oxygen species. CaMKII (Ca2+/calmodulin-dependent protein
      kinase II) is vital for normal Ca2+ homeostasis, but excessive CaMKII activity
      contributes to abnormal Ca2+ homeostasis and arrhythmias in cardiomyocytes.
      Reactive oxygen species induce CaMKII to become autonomously active. We
      hypothesized that genetic inhibition of CaMKII oxidation (ox-CaMKII) in a mouse
      model of Duchenne muscular dystrophy can alleviate abnormal Ca2+ homeostasis,
      thus, preventing ventricular arrhythmia. The objective of this study was to test
      if selective loss of ox-CaMKII affects ventricular arrhythmias in the mdx mouse
      model of Duchenne muscular dystrophy. METHODS AND RESULTS: 5-(6)-Chloromethyl-2,7
      dichlorodihydrofluorescein diacetate staining revealed increased reactive oxygen
      species production in ventricular myocytes isolated from mdx mice, which
      coincides with elevated ventricular ox-CaMKII demonstrated by Western blotting.
      Genetic inhibition of ox-CaMKII by knockin replacement of the regulatory domain
      methionines with valines (MM-VV [CaMKII M281/282V]) prevented ventricular
      tachycardia in mdx mice. Confocal calcium imaging of ventricular myocytes
      isolated from mdx:MM-VV mice revealed normalization of intracellular Ca2+ release
      events compared with cardiomyocytes from mdx mice. Abnormal action potentials
      assessed by optical mapping in mdx mice were also alleviated by genetic
      inhibition of ox-CaMKII. Knockout of the NADPH oxidase regulatory subunit p47
      phox normalized elevated ox-CaMKII, repaired intracellular Ca2+ homeostasis, and
      rescued inducible ventricular arrhythmias in mdx mice. CONCLUSIONS: Inhibition of
      reactive oxygen species or ox-CaMKII protects against proarrhythmic intracellular
      Ca2+ handling and prevents ventricular arrhythmia in a mouse model of Duchenne
      muscular dystrophy.

PMID- 29654127
TI  - Health Care Costs After Cardiac Arrest in the United States.
AB  - BACKGROUND: This study was designed to estimate the costs of index
      hospitalizations after cardiac arrest in the United States. METHODS AND RESULTS:
      We used the US Nationwide Inpatient Sample (2003-2012) to identify patients with
      cardiac arrest. Log transformation of inflation-adjusted cost was determined for
      care to patient outcomes. Overall, an estimated 1 387 396 patients were
      hospitalized after cardiac arrest. The mean age of the cohort was 66 years, 45%
      were women, and the majority were white. Inpatient procedures included coronary
      angiography (15%), percutaneous coronary intervention (7%), intra-aortic balloon
      pump (4.4%), therapeutic hypothermia (1.1%), and mechanical circulatory support
      (0.1%). The rates of therapeutic hypothermia increased from zero in 2003 to 2.7%
      in 2012 (P<0.001). Both hospital charges and inflation-adjusted cost increased
      linearly over time. In a multivariate analysis, predictors of inflation-adjusted
      cost included large hospital size, urban teaching hospital, and length of stay.
      Among comorbidities, atrial fibrillation or fluid and electrolytes imbalance was
      most associated with cost. Among selected interventions, the cost was
      significantly increased with automatic implantable cardioverter defibrillators
      (odds ratio, 1.83; P<0.001), intra-aortic balloon pump (odds ratio, 1.50;
      P<0.001), hypothermia (odds ratio, 1.28; P<0.001), and extracorporeal membrane
      oxygenation (odds ratio, 2.38; P<0.001). CONCLUSIONS: In the period between 2003
      and 2012, postcardiac arrest hospitalizations resulted in a steady rise in
      associated health care cost, likely related to increased length of stay, medical
      procedures, and systems of care. Although targeted cost containment for
      postarrest interventions may reduce the finance burden, there is an increasing
      need for funding research into prediction and prevention of cardiac arrest, which
      offers greater societal benefit.

PMID- 29654128
TI  - New Substrate-Guided Method of Predicting Slow Conducting Isthmuses of
      Ventricular Tachycardia: Preliminary Analysis to the Combined Use of Voltage
      Limit Adjustment and Fast-Fourier Transform Analysis.
AB  - BACKGROUND: Several conducting channels of ventricular tachycardia (VT) can be
      identified using voltage limit adjustment (VLA) of substrate mapping. However,
      the sensitivity or specificity to predict a VT isthmus is not high by using VLA
      alone. This study aimed to evaluate the efficacy of the combined use of VLA and
      fast-Fourier transform analysis to predict VT isthmuses. METHODS AND RESULTS: VLA
      and fast-Fourier transform analyses of local ventricular bipolar electrograms
      during sinus rhythm were performed in 9 postinfarction patients who underwent
      catheter ablation for a total of 13 monomorphic VTs. Relatively higher voltage
      areas on an electroanatomical map were defined as high voltage channels (HVCs),
      and relatively higher fast-Fourier transform areas were defined as high-frequency
      channels (HFCs). HVCs were classified into full or partial HVCs (the entire or
      >30% of HVC can be detectable, respectively). Twelve full HVCs were identified in
      7 of 9 patients. HFCs were located on 7 of 12 full HVCs. Five VT isthmuses (71%)
      were included in the 7 full HVC+/HFC+ sites, whereas no VT isthmus was found in
      the 5 full HVC+/HFC- sites. HFCs were identical to 9 of 16 partial HVCs. Eight VT
      isthmuses (89%) were included in the 9 partial HVC+/HFC+ sites, whereas no VT
      isthmus was found in the 7 partial HVC+/HFC- sites. All HVC+/HFC+ sites predicted
      VT isthmus with a sensitivity of 100% and a specificity of 80%. CONCLUSIONS:
      Combined use of VLA and fast-Fourier transform analysis may be a useful method to
      detect VT isthmuses.

PMID- 29654129
TI  - Recurrent Atrial Fibrillation After Initial Long-Term Ablation Success:
      Electrophysiological Findings and Outcomes of Repeat Ablation Procedures.
AB  - BACKGROUND: Atrial fibrillation recurrence after initial long-term success of
      catheter ablation has been described, yet not well studied. We assessed the
      electrophysiological findings and outcomes of repeat ablation procedures in this
      setting. METHODS AND RESULTS: Between 2000 and 2015, 10 378 patients underwent
      atrial fibrillation ablation and were enrolled in a prospectively maintained data
      registry. From this registry, we included all 137 consecutive patients who had
      initial long-term success, defined as freedom from recurrent arrhythmia for >36
      months off antiarrhythmics, then underwent repeat ablation for recurrent atrial
      fibrillation. The median arrhythmia-free period that defined long-term success
      was 52 months (41-68 months). In redo ablations, reconnection along at least one
      of the pulmonary veins (PVs) was found in 111 (81%) patients. Reconnection along
      a left superior, left inferior, right superior, and right inferior PV was found
      in 64%, 62%, 50%, and 54% of patients, respectively, and were reisolated.
      Additional non-PV ablations were performed in 127 (92.7%) patients: posterior
      wall (46%), septal to right PVs (49%), superior vena cava (35%), roof lines
      (52%), and cavotricuspid isthmus (33%). After a median follow-up of 17 months (5
      36.9 months), 103 patients (75%) were arrhythmia free (79 off antiarrhythmics, 24
      on antiarrhythmics). CONCLUSIONS: PV reconnection is the most common
      electrophysiological finding in patients with atrial fibrillation recurrence
      after long-term success, but with lower rates than what had been reported for
      early recurrences. In our experience, repeat ablations in this setting involve
      complex ablation approaches to reisolate the PVs and modify the atrial substrate
      and are associated with good success rates.

PMID- 29654130
TI  - Left Ventricular Isovolumetric Relaxation Time Is Prolonged in Fetal Long-QT
      Syndrome.
AB  - BACKGROUND: Long-QT syndrome (LQTS), an inherited cardiac repolarization
      disorder, is an important cause of fetal and neonatal mortality. Detecting LQTS
      prenatally is challenging. A fetal heart rate (FHR) less than third percentile
      for gestational age is specific for LQTS, but the sensitivity is only ~50%. Left
      ventricular isovolumetric relaxation time (LVIRT) was evaluated as a potential
      diagnostic marker for fetal LQTS. METHODS AND RESULTS: LV isovolumetric
      contraction time, LV ejection time, LVIRT, cycle length, and FHR were measured
      using pulsed Doppler waveforms in fetuses. Time intervals were expressed as
      percentages of cycle length, and the LV myocardial performance index was
      calculated. Single measurements were stratified by gestational age and compared
      between LQTS fetuses and controls. Receiver-operator curves were performed for
      FHR and normalized LVIRT (N-LVIRT). A linear mixed-effect model including
      multiple measurements was used to analyze trends in FHR, N-LVIRT, and LV
      myocardial performance index. There were 33 LQTS fetuses and 469 controls
      included. In LQTS fetuses, the LVIRT was prolonged in all gestational age groups
      (P<0.001), as was the N-LVIRT. The best cutoff to diagnose LQTS was N-LVIRT
      >=11.3 at <=20 weeks (92% sensitivity, 70% specificity). Simultaneous analysis of
      N-LVIRT and FHR improved the sensitivity and specificity for LQTS (area under the
      curve=0.96; 95% confidence interval, 0.82-1.00 at 21-30 weeks). N-LVIRT, LV
      myocardial performance index, and FHR trends differed significantly between LQTS
      fetuses and controls through gestation. CONCLUSIONS: The LVIRT is prolonged in
      LQTS fetuses. Findings of a prolonged N-LVIRT and sinus bradycardia can improve
      the prenatal detection of fetal LQTS.

PMID- 29654131
TI  - Lesion Index-Guided Ablation Facilitates Continuous, Transmural, and Durable
      Lesions in a Porcine Recovery Model.
AB  - BACKGROUND: The Lesion Index (LSI) is a proprietary algorithm from Abbott Medical
      combining contact force, radiofrequency application duration, and radiofrequency
      current. It can be displayed during ablation with the TactiCath contact force
      catheter. The LSI Index was designed to provide real-time lesion formation
      feedback and is hypothesized to estimate the lesion diameter. METHODS AND
      RESULTS: Before ablation, animals underwent cardiac computed tomography to assess
      atrial tissue thickness. Ablation lines (n=2-3 per animal) were created in the
      right atrium of 7 Gottingen mini pigs with point lesions (25 W). Within each line
      of ablation, the catheter tip was moved a prescribed distance (D/mm) according to
      1 of 3 strategies: D=LSI+0 mm; D=LSI+2 mm; or D=LSI+4 mm. Two weeks after
      ablation, serial sections of targeted atrial tissue were examined histologically
      to identify gaps in transmural ablation. LSI-guided lines had a lower incidence
      of histological gaps (4 gaps in 69 catheter moves, 5.8%) than LSI+2 mm lines (7
      gaps in 33 catheter moves, 21.2%) and LSI+4 mm lines (15 gaps in 23 catheter
      moves, 65.2%, P<0.05 versus D=LSI). DeltaLSI was calculated retrospectively as
      the distance between 2 adjacent lesions above the mean LSI of the 2 lesions.
      DeltaLSI values of <=1.5 were associated with no gaps in transmural ablation.
      CONCLUSIONS: In this model of chronic atrial ablation, delivery of uninterrupted
      transmural linear lesions may be facilitated by using LSI to guide catheter
      movement. When DeltaLSI between adjacent lesions is <=1.5 mm, no gaps in atrial
      linear lesions should be expected.

PMID- 29654132
TI  - Mortality and Sudden Cardiac Death Risk Stratification Using the Noninvasive
      Combination of Wide QRS Duration and Late Gadolinium Enhancement in Idiopathic
      Dilated Cardiomyopathy.
AB  - BACKGROUND: The aim of this study was to investigate whether the combination of
      QRS duration >=120 ms (wide QRS duration [wQRS]) and late gadolinium enhancement
      (LGE) is a precise prognostic indicator for dilated cardiomyopathy. METHODS AND
      RESULTS: We investigated the association between the combination of LGE plus wQRS
      and the primary end point (all-cause death) and a composite of sudden cardiac
      death (SCD) or aborted SCD in 531 patients with dilated cardiomyopathy. We also
      analyzed the association between the combination of LGE and wQRS and these end
      points among patients with a class I indication for implantable cardioverter
      defibrillator implantation. We divided study patients into 3 groups according to
      LGE status and QRS duration: 2 negative indices (LGE negative and narrow QRS), 1
      positive index (LGE positive or wQRS), or 2 positive indices (LGE positive and
      wQRS), and followed them for 3.8 years. Multivariable Cox regression analysis
      identified 2 positive indices as a significant predictor of all-cause death
      (hazard ratio, 4.29 [1.19-15.47]; P=0.026). Among 317 patients with a class I
      indication for implantable cardioverter defibrillator, the 5-year event rate of
      SCD or aborted SCD was the lowest in the 2 negative indices group (1.4%). With
      propensity score-matching cohorts, the 2 negative indices group had a
      significantly lower event rate of SCD or aborted SCD than the other 2 groups
      (hazard ratio, 0.12 [0.01-0.97]; P=0.046). CONCLUSIONS: The combination of LGE
      and wQRS provides additional prognostic stratification compared with LGE status
      alone and might improve the appropriate use of implantable cardioverter
      defibrillator therapy in patients with dilated cardiomyopathy.

PMID- 29654133
TI  - Understanding Mechanisms of Cardiac Resynchronization Therapy Response to Improve
      Patient Selection and Outcomes.

PMID- 29654134
TI  - Letter by Penela et al Regarding Article, "Standard Ablation Versus Magnetic
      Resonance Imaging-Guided Ablation in the Treatment of Ventricular Tachycardia".

PMID- 29654135
TI  - Creation of Continuous and Transmural Radiofrequency Lesions.

PMID- 29654136
TI  - Recurrence Post-Atrial Fibrillation Ablation: Think Outside the Pulmonary Veins.

PMID- 29654137
TI  - Fast and the Furious: Electrogram Drift: Dynamic Analysis of Acquired
      Electrograms to Optimize Discrimination of Ventricular Tachycardia Substrate.

PMID- 29654138
TI  - Response by Zghaib et al to Letter Regarding Article, "Standard Ablation Versus
      Magnetic Resonance Imaging-Guided Ablation in the Treatment of Ventricular
      Tachycardia".

PMID- 29654139
TI  - Implementation and evaluation of a pharmacist-led electronic visit program for
      diabetes and anticoagulation care in a patient-centered medical home.
AB  - PURPOSE: Results of a study evaluating quality-of-care, financial, and patient
      satisfaction outcomes of pharmacist-conducted telehealth visits for diabetes
      management and warfarin monitoring are reported. METHODS: A retrospective pre
      post study was conducted to determine the impact of an electronic visit (e-visit)
      program targeting 2 groups of outpatients: adults with uncontrolled diabetes and
      warfarin-treated adults performing patient self-testing (PST) for monitoring of
      International Normalized Ratio (INR) values. RESULTS: A total of 36 patients
      participated in the e-visit program during the 2-year study period. Among
      warfarin-treated patients, the percentage of INR values in the desired range
      increased relative to preenrollment values (from 62.5% to 72.7%, p = 0.07), and
      the frequency of extreme INR values (values of <1.5 or >5.0) decreased (from 4.8%
      to 0.01%, p = 0.01); the margin per patient was $300 during the first year and
      $191 annually thereafter. In the diabetes group, a decrease from baseline in
      glycosylated hemoglobin values of 3.4 percentage points was observed at 5.7
      months after enrollment (p < 0.001), with significant improvements in frequencies
      of statin use, aspirin use, and blood pressure control; the margin was $100 per
      patient. The overall median patient satisfaction survey score was 39 of 40.
      CONCLUSION: An online e-visit model for warfarin monitoring was an efficient,
      safe, and cost-effective method for implementing PST. Pharmacist-led management
      of diabetes through e-visits, often in combination with in-person visits,
      generated revenue while significantly improving clinical outcomes.

PMID- 29654140
TI  - Optimization of clinical pharmacy specialists at Veterans Affairs facilities.

PMID- 29654141
TI  - Advancement of clinical pharmacy practice through intervention capture.
AB  - PURPOSE: The methods and processes utilized to deploy the Pharmacists Achieve
      Results with Medications Documentation (PhARMD) Project intervention template
      across the largest integrated healthcare system in the United States are
      described. SUMMARY: The PhARMD Project team at the Department of Veterans Affairs
      (VA) designed, developed, and deployed a standardized template within VA's
      electronic health record (EHR) that allows the clinical pharmacy specialist (CPS)
      to efficiently document select interventions made during patient care encounters
      that specifically contribute to the overall care provided and patient outcomes.
      The template is completed by the CPSs as part of progress note documentation
      within the EHR. Using point-and-click functionality, a CPS selects the check
      boxes corresponding to specific interventions made during that patient care
      encounter. This improves workflow and negates the need to document interventions
      in a separate software system, streamlining documentation. The implementation and
      use of the PhARMD template at each VA facility are voluntary. From October 1,
      2016, to September 30, 2017, 4,728 CPSs documented 3,805,323 interventions during
      2,384,771 patient care encounters. These interventions were documented across
      592,126 unique patients, with a mean of 6.4 interventions per patient during this
      period. Most interventions (95%) were performed by CPSs functioning as advanced
      practice providers and with autonomous prescriptive authority authorized under
      their scope of practice. CONCLUSION: The PhARMD template demonstrated that the
      capture of clinical pharmacy interventions and outcomes can be achieved across a
      large integrated healthcare system by thousands of CPSs in numerous practice
      settings.

PMID- 29654142
TI  - Neonatal Hypoglycemia Following Diet-Controlled and Insulin-Treated Gestational
      Diabetes Mellitus.
AB  - OBJECTIVE: To assess the risk of neonatal hypoglycemia following diet-controlled
      and insulin-treated gestational diabetes mellitus (GDM) and how it relates to
      birth weight. RESEARCH DESIGN AND METHODS: Prospective cohort study included term
      neonates born after GDM from January 2013 through December 2015 at the University
      Medical Center Utrecht (Utrecht, the Netherlands). Routine screening of neonatal
      blood glucose levels was performed at 1, 3, 6, 12, and 24 h after birth. Main
      outcome measures were neonatal hypoglycemia defined as blood glucose <=36 mg/dL
      (severe) and <=47 mg/dL (mild). RESULTS: A total of 506 neonates were included,
      born after pregnancies complicated by GDM treated either with insulin (22.5%) or
      without insulin (77.5%). The incidence of mild and severe hypoglycemia was
      similar in the insulin-treated and diet-controlled groups (33 vs. 35%, P = 0.66;
      and 20 vs. 21%, P = 0.79). A birth weight >90th centile was seen in 17.2% of all
      infants. Although children with a birth weight >90th centile had the highest risk
      for hypoglycemia, the vast majority of hypoglycemia (78.6%) was detected in those
      with a birth weight <90th centile. Over 95% of all hypoglycemia occurred within
      12 h after birth. CONCLUSIONS: Routine screening for neonatal hypoglycemia
      following pregnancies complicated by GDM reveals high incidence of both mild and
      severe hypoglycemia for both diet-controlled and insulin-treated GDM and across
      the full range of birth weight centiles. We propose routine blood glucose
      screening for neonatal hypoglycemia within the first 12 h of life in all neonates
      after GDM, irrespective of maternal insulin use or birth weight.

PMID- 29654143
TI  - Reply to Mortensen et al.: The zymogen form of complement component C1.

PMID- 29654144
TI  - Models of the complement C1 complex.

PMID- 29654145
TI  - Endoplasmic reticulum stress activates SRC, relocating chaperones to the cell
      surface where GRP78/CD109 blocks TGF-beta signaling.
AB  - The discovery that endoplasmic reticulum (ER) luminal chaperones such as
      GRP78/BiP can escape to the cell surface upon ER stress where they regulate cell
      signaling, proliferation, apoptosis, and immunity represents a paradigm shift.
      Toward deciphering the mechanisms, we report here that, upon ER stress, IRE1alpha
      binds to and triggers tyrosine kinase SRC activation, leading to ASAP1
      phosphorylation and Golgi accumulation of ASAP1 and Arf1-GTP, resulting in KDEL
      receptor dispersion from the Golgi and suppression of retrograde transport. At
      the cell surface, GRP78 binds to and acts in concert with a
      glycosylphosphatidylinositol-anchored protein, CD109, in blocking TGF-beta
      signaling by promoting the routing of the TGF-beta receptor to the caveolae,
      thereby disrupting its binding to and activation of Smad2. Collectively, we
      uncover a SRC-mediated signaling cascade that leads to the relocalization of ER
      chaperones to the cell surface and a mechanism whereby GRP78 counteracts the
      tumor-suppressor effect of TGF-beta.

PMID- 29654146
TI  - Role of PD-1 during effector CD8 T cell differentiation.
AB  - PD-1 (programmed cell death-1) is the central inhibitory receptor regulating CD8
      T cell exhaustion during chronic viral infection and cancer. Interestingly, PD-1
      is also expressed transiently by activated CD8 T cells during acute viral
      infection, but the role of PD-1 in modulating T cell effector differentiation and
      function is not well defined. To address this question, we examined the
      expression kinetics and role of PD-1 during acute lymphocytic choriomeningitis
      virus (LCMV) infection of mice. PD-1 was rapidly up-regulated in vivo upon
      activation of naive virus-specific CD8 T cells within 24 h after LCMV infection
      and in less than 4 h after peptide injection, well before any cell division had
      occurred. This rapid PD-1 expression by CD8 T cells was driven predominantly by
      antigen receptor signaling since infection with a LCMV strain with a mutation in
      the CD8 T cell epitope did not result in the increase of PD-1 on antigen-specific
      CD8 T cells. Blockade of the PD-1 pathway using anti-PD-L1 or anti-PD-1
      antibodies during the early phase of acute LCMV infection increased mTOR
      signaling and granzyme B expression in virus-specific CD8 T cells and resulted in
      faster clearance of the infection. These results show that PD-1 plays an
      inhibitory role during the naive-to-effector CD8 T cell transition and that the
      PD-1 pathway can also be modulated at this stage of T cell differentiation. These
      findings have implications for developing therapeutic vaccination strategies in
      combination with PD-1 blockade.

PMID- 29654147
TI  - Ligand metathesis as rational strategy for the synthesis of cubane-type
      heteroleptic iron-sulfur clusters relevant to the FeMo cofactor.
AB  - Molybdenum-dependent nitrogenases catalyze the transformation of dinitrogen into
      ammonia under ambient conditions. The active site (FeMo cofactor) is the
      structurally and electronically complex weak-field metal cluster [MoFe7S9C] built
      of Fe4S3 and MoFe3S3C portions connected by three sulfur bridges and containing
      an interstitial carbon atom centered in an Fe6 trigonal prism. Chemical synthesis
      of this cluster is a major challenge in biomimetic inorganic chemistry. One
      synthetic approach of core ligand metathesis has been developed based on the
      design and synthesis of unprecedented incomplete ([(Tp*)WFe2S3Q3]-) and complete
      ([(Tp*)WFe3S3Q4]2-) cubane-type clusters containing bridging halide (Q = halide).
      These clusters are achieved by template-assisted assembly in the presence of
      sodium benzophenone ketyl reductant; products are controlled by reaction
      stoichiometry. Incomplete cubane clusters are subject to a variety of metathesis
      reactions resulting in substitution of a MU2-bridging ligand with other bridges
      such as N3-, MeO-, and EtS- Reactions of complete cubanes with Me3SiN3 and S8
      undergo a redox metathesis process and lead to core ligand displacement and
      formation of [(Tp*)WFe3S3(MU3-Q)Cl3]- (Q = Me3SiN2-, S2-). This work affords
      entry to a wide variety of heteroleptic clusters derivable from incomplete and
      complete cubanes; examples are provided. Among these is the cluster
      [(Tp*)WFe3S3(MU3-NSiMe3)Cl3]-, one of the very few instances of a synthetic Fe-S
      cluster containing a light atom (C, N, O) in the core, which constitutes a close
      mimic of the [MoFe3S3C] fragment in FeMo cofactor. Superposition of them and
      comparison of metric information disclose a clear structural relationship [Tp* =
      tris(3,5-dimethyl-1-pyrazolyl)hydroborate(1-)].

PMID- 29654150
TI  - Cancer Research: Embracing the Complexity of Cancer and Emergence of Truth.

PMID- 29654148
TI  - DRUG-NEM: Optimizing drug combinations using single-cell perturbation response to
      account for intratumoral heterogeneity.
AB  - An individual malignant tumor is composed of a heterogeneous collection of single
      cells with distinct molecular and phenotypic features, a phenomenon termed
      intratumoral heterogeneity. Intratumoral heterogeneity poses challenges for
      cancer treatment, motivating the need for combination therapies. Single-cell
      technologies are now available to guide effective drug combinations by accounting
      for intratumoral heterogeneity through the analysis of the signaling
      perturbations of an individual tumor sample screened by a drug panel. In
      particular, Mass Cytometry Time-of-Flight (CyTOF) is a high-throughput single
      cell technology that enables the simultaneous measurements of multiple ([Formula:
      see text]40) intracellular and surface markers at the level of single cells for
      hundreds of thousands of cells in a sample. We developed a computational
      framework, entitled Drug Nested Effects Models (DRUG-NEM), to analyze CyTOF
      single-drug perturbation data for the purpose of individualizing drug
      combinations. DRUG-NEM optimizes drug combinations by choosing the minimum number
      of drugs that produce the maximal desired intracellular effects based on nested
      effects modeling. We demonstrate the performance of DRUG-NEM using single-cell
      drug perturbation data from tumor cell lines and primary leukemia samples.

PMID- 29654152
TI  - The Plausibility of the Obesity Paradox in Cancer-Response-Reply to Point.

PMID- 29654151
TI  - The Plausibility of Obesity Paradox in Cancer-Point.
AB  - In contrast to the convincing evidence that obesity (measured by body mass index,
      BMI) increases the risk of many different types of cancer, there is an ambiguity
      in the role of obesity in survival among cancer patients. Some studies suggested
      that higher BMI decreased mortality risk in cancer patients, a phenomenon called
      the obesity paradox. The spurious positive association between BMI and cancer
      survival is likely to be explained by several methodologic limitations including
      confounding, reverse causation, and collider stratification bias. Also, the
      inadequacy of BMI as a measure of body fatness in cancer patients commonly
      experiencing changes in body weight and body composition may have resulted in the
      paradox. Other factors contributing to the divergent results in literature are
      significant heterogeneity in study design and method (e.g., study population,
      follow-up length); time of BMI assessment (pre-, peri-, or post-diagnosis); and
      lack of consideration for variability in the strength and directions of
      associations by age, sex, race/ethnicity, and cancer subtype. Robust but
      practical methods to accurately assess body fatness and body compositions and
      weight trajectories in cancer survivors are needed to advance this emerging field
      and to develop weight guidelines to improve both the length and the quality of
      cancer survival. Cancer Res; 78(8); 1898-903. (c)2018 AACR.

PMID- 29654154
TI  - Evidence for an Overweight Paradox in Cancer: Insights from Body Composition
      Reply to Counterpoint.

PMID- 29654153
TI  - The Importance of Body Composition in Explaining the Overweight Paradox in Cancer
      Counterpoint.
AB  - Despite a greater risk of cancer associated with higher BMI, overweight (BMI 25
      <30 kg/m2) and class I obese (BMI 30-<35 kg/m2) patients often have a
      paradoxically lower risk of overall mortality after a cancer diagnosis, a
      phenomenon called the "obesity paradox." Only when patients exceed a BMI >=35
      kg/m2 are elevations in mortality risk consistently noted. This paradox has been
      dismissed as the result of methodologic bias, which we will describe and debate
      here. However, even if such bias influences associations, there is growing
      evidence that body composition may in part explain the paradox. This phenomenon
      may more accurately be described as a BMI paradox. That is, BMI is a poor proxy
      for adiposity and does not distinguish muscle from adipose tissue, nor describe
      adipose tissue distribution. Low muscle mass is associated with higher risk of
      recurrence, overall and cancer-specific mortality, surgical complications, and
      treatment-related toxicities. Patients with who are overweight or obese have on
      average higher levels of muscle than their normal-weight counterparts. Also,
      there is some evidence that patients with moderate levels of subcutaneous adipose
      tissue may have lower mortality. More research utilizing body composition is
      needed to clarify the effects of adiposity on cancer mortality. Cancer Res;
      78(8); 1906-12. (c)2018 AACR.

PMID- 29654155
TI  - ME1 Regulates NADPH Homeostasis to Promote Gastric Cancer Growth and Metastasis.
AB  - Genomic alterations of tumor suppressorsoften encompass collateral protein-coding
      genes that create therapeutic vulnerability to further inhibition of their
      paralogs. Here, we report that malic enzyme 2 (ME2) is frequently hemizygously
      codeleted with SMAD4 in gastric cancer. Its isoenzyme ME1 was upregulated to
      replenish the intracellular reducing equivalent NADPH and to maintain redox
      homeostasis. Knockdown of ME1 significantly depleted NADPH, induced high levels
      of reactive oxygen species (ROS), and ultimately cell apoptosis under oxidative
      stress conditions, such as glucose starvation and anoikis, in ME2-underexpressed
      cells. Moreover, ME1 promoted tumor growth, lung metastasis, and peritoneal
      dissemination of gastric cancer in vivo Intratumoral injection of ME1 siRNA
      significantly suppressed tumor growth in cell lines and patient-derived xenograft
      based models. Mechanistically, ME1 was transcriptionally upregulated by ROS in an
      ETV4-dependent manner. Overexpression of ME1 was associated with shorter overall
      and disease-free survival in gastric cancer. Altogether, our results shed light
      on crucial roles of ME1-mediated production of NADPH in gastric cancer growth and
      metastasis.Significance: These findings reveal the role of malic enzyme in growth
      and metastasis.Graphical Abstract:
      http://cancerres.aacrjournals.org/content/canres/78/8/1972/F1.large.jpg Cancer
      Res; 78(8); 1972-85. (c)2018 AACR.

PMID- 29654156
TI  - Immunohistochemical Expression of Cortactin and Focal Adhesion Kinase Predicts
      Recurrence Risk and Laryngeal Cancer Risk Beyond Histologic Grading.
AB  - Background: Cortactin (CTTN) and the focal adhesion kinase (FAK) are two major
      candidate genes to, respectively, drive 11q13- and 8q24-associated aggressive
      behavior in various cancers. Recent evidence uncovered their clinical relevance
      in early stages of tumorigenesis as promising biomarkers for cancer risk
      assessment.Methods: Using a multicenter validation study, CTTN and FAK expression
      was evaluated by immunohistochemistry (IHC) in a cohort of 109 patients with
      laryngeal precancerous lesions, and correlated with clinicopathologic parameters
      and laryngeal cancer risk. The pathophysiologic role of CTTN and FAK was further
      investigated using functional studies in cellular models.Results: Positive CTTN
      and FAK expression (scores 2 and 3) was detected in 49 (41%) and 35 (32%)
      laryngeal dysplasias, respectively. Univariate Cox analysis showed that CTTN and
      FAK expression but not histologic grading was significantly associated with both
      recurrence risk and laryngeal cancer risk. Patients carrying strong CTTN- or FAK
      expressing lesions (score 3) experienced the highest laryngeal cancer incidence
      (log-rank P < 0.001). In multivariate stepwise analysis, FAK expression [HR =
      13.91; 95% CI, 4.82-40.15; P < 0.001] and alcohol consumption (HR = 2.22; 95%
      confidence interval, 1.17-4.20; P = 0.014) were significant independent
      predictors of laryngeal cancer development. Targeting FAK by either RNAi or
      pharmacologic inhibitors effectively blocked cell growth, colony formation, and
      invasion into 3D collagen matrices.Conclusions: CTTN and FAK emerge as powerful
      predictors of laryngeal cancer risk and recurrence risk beyond histologic
      grading.Impact: Our work supports the applicability of IHC CTTN and FAK as
      complementary markers for risk stratification in patients with laryngeal
      precancerous lesions. Cancer Epidemiol Biomarkers Prev; 27(7); 805-13. (c)2018
      AACR.

PMID- 29654157
TI  - Reducing Variations in Neonatal Outcomes: Look at Practices, Systems, and the
      Patient.

PMID- 29654158
TI  - Variability of Very Low Birth Weight Infant Outcome and Practice in Swiss and US
      Neonatal Units.
AB  - OBJECTIVES: Outcomes of very preterm infants vary considerably between health
      care facilities. Our objective was to compare outcome and practices between the
      Swiss Neonatal Network (SNN) and US members of the Vermont Oxford Network (US
      VON). METHODS: Retrospective observational study including all live-born infants
      with a birth weight between 501 and 1500 g as registered by SNN and US-VON
      between 2012 and 2014. We performed multivariable and propensity score-matched
      analyses of neonatal outcome by adjusting for case-mix, race, prenatal care, and
      unit-level factors, and compared indirectly standardized practices. RESULTS: A
      total of 123 689 infants were born alive in 696 US-VON units and 2209 infants
      were born alive in 13 SNN units. Adjusted risk ratios (aRRs) for the composite
      "death or major morbidity" (aRR: 0.56, 95% confidence interval: 0.51-0.62) and
      all other outcomes were either comparable or lower in SNN except for mortality,
      for which aRR was higher (aRR: 1.28, 95% confidence interval: 1.09-1.50).
      Propensity score matching and restricting the analysis to infants for which we
      expect no survival bias, because both networks routinely initiate intensive care
      at birth, revealed comparable aRR. Variations in observed practices between SNN
      and US-VON were large. CONCLUSIONS: The SNN units had a significantly lower risk
      ratio for death or major morbidity. Despite higher mortality, this difference is
      independent of survival bias. The higher delivery room mortality reflects the SNN
      practice to favor primary nonintervention for infants born <24 completed
      gestational weeks. We propose further research into which practice differences
      have the strongest beneficial impact.

PMID- 29654160
TI  - Axonal mRNA transport and translation at a glance.
AB  - Localization and translation of mRNAs within different subcellular domains
      provides an important mechanism to spatially and temporally introduce new
      proteins in polarized cells. Neurons make use of this localized protein synthesis
      during initial growth, regeneration and functional maintenance of their axons.
      Although the first evidence for protein synthesis in axons dates back to 1960s,
      improved methodologies, including the ability to isolate axons to purity, highly
      sensitive RNA detection methods and imaging approaches, have shed new light on
      the complexity of the transcriptome of the axon and how it is regulated.
      Moreover, these efforts are now uncovering new roles for locally synthesized
      proteins in neurological diseases and injury responses. In this Cell Science at a
      Glance article and the accompanying poster, we provide an overview of how axonal
      mRNA transport and translation are regulated, and discuss their emerging links to
      neurological disorders and neural repair.

PMID- 29654161
TI  - The filamin-B-refilin axis - spatiotemporal regulators of the actin-cytoskeleton
      in development and disease.
AB  - During development, cycles of spatiotemporal remodeling of higher-order networks
      of actin filaments contribute to control cell fate specification and
      differentiation. Programs for controlling these dynamics are hard-wired into
      actin-regulatory proteins. The filamin family of actin-binding proteins exert
      crucial mechanotransduction and signaling functions in tissue morphogenesis.
      Filamin-B (FLNB) is a key player in chondrocyte progenitor differentiation for
      endochondral ossification. Biallelic loss-of-function mutations or gain-of
      function mutations in FLNB cause two groups of skeletal disorders that can be
      attributed to either the loss of repressive function on TGF-beta signaling or a
      disruption in mechanosensory properties, respectively. In this Review, we
      highlight a unique family of vertebrate-specific short-lived filamin-binding
      proteins, the refilins (refilin-A and refilin-B), that modulate filamin-dependent
      actin crosslinking properties. Refilins are downstream TGF-beta effectors in
      epithelial cells. Double knockout of both refilin-A and refilin-B in mice results
      in precocious ossification of some axial skeletal elements, leading to
      malformations that are similar to those seen in FLNB-deficient mice. Based on
      these findings, we present a model summarizing the role of refilins in regulating
      the mechanosensory functions of FLNB during skeletal development. We also discuss
      the possible contribution of refilins to FLNB-related skeletal pathologies that
      are associated with gain-of-function mutations.

PMID- 29654162
TI  - Association between PXR polymorphisms and cancer risk: a systematic review and
      meta-analysis.
AB  - Current studies have explored the correlation between the single nucleotide
      polymorphisms (SNPs) of pregnane X receptor (PXR) and cancer risk. However, the
      findings were conflicting. Hence, we performed a comprehensive review and meta
      analysis for these researches to determine the effect of PXR polymorphisms on the
      risk of cancer. Eligible publications were collected based on a series of
      rigorous inclusion and exclusion criteria. In consequence, a total of eight case
      control studies (from seven citations) covering 11143 cases and 12170 controls
      were involved in a meta-analysis of ten prevalent PXR SNPs (rs10504191 G/A,
      rs3814058 C/T, rs6785049 A/G, rs1464603 A/G, rs1523127 A/C, rs2276706 G/A,
      rs2276707 C/T, rs3732360 C/T, rs3814055 C/T, rs3814057 A/C). The correlations
      between PXR SNPs and cancer risk were estimated by odds ratios (ORs) with their
      95% confidence intervals (95%CIs). The findings demonstrated that rs3814058
      polymorphism (CT compared with CC: pooled OR = 1.280, P=6.36E-05; TT compared
      with CC: pooled OR = 1.663, P=2.40E-04; dominant model: pooled OR = 1.382,
      P=2.58E-08; recessive model: pooled OR = 1.422, P=0.002; T compared with C:
      pooled OR = 1.292, P=6.35E-05) and rs3814057 polymorphism (AC compared with AA:
      pooled OR = 1.170, P=0.036; dominant model: pooled OR = 1.162, P=0.037) were
      associated with the risk of overall cancer. In stratified analyses, rs3814058
      polymorphism was revealed to increase the cancer risk in lung cancer subgroup. In
      summary, this meta-analysis indicates that the rs3814057 and rs3814058
      polymorphisms of PXR gene play crucial roles in the pathogenesis of cancer and
      may be novel biomarkers for cancer-forewarning in overall population or in some
      particular subgroups.

PMID- 29654163
TI  - Association of FcepsilonRIbeta polymorphisms with risk of asthma and allergic
      rhinitis: evidence based on 29 case-control studies.
AB  - PURPOSE: Accumulating evidence has shown that allergic diseases are caused by a
      complex interaction of genetic and environmental factors, some single nucleotide
      polymorphisms (SNPs) existing in high-affinity IgE receptor beta chain
      (FcepsilonRIbeta) are potential risk factors for allergic diseases. However, the
      results have been inconsistent and inconclusive due to the limited statistical
      power in individual study. Thus, we conducted a meta-analysis to systematically
      evaluate the association between FcepsilonRIbeta SNPs and allergic diseases risk.
      METHODS: Eligible studies were collected from PubMed, Embase, Web of Science,
      Chinese National Knowledge Infrastructure, and WanFang databases. Pooled odd
      ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were calculated
      to assess the strength of the relationships between five polymorphisms (E237G, 
      109 C/T, RsaI_in2, RsaI_ex7, and I181L) and the risk of allergic diseases by
      using five genetic models. In addition, the stability of our analysis was
      evaluated by publication bias, sensitivity, and heterogeneity analysis. RESULTS:
      Overall, a total of 29 case-control studies were included in this meta-analysis.
      We found that E237G (B vs. A: OR = 1.28, 95% CI = 1.06-1.53, P<0.001, I2 = 63.1%)
      and -109 C/T (BB vs. AA + AB: OR = 1.58, 95%CI = 1.26-1.98, P<0.001, I2 = 66.4%)
      were risk factors for allergic diseases. CONCLUSION: Our meta-analysis suggests
      that polymorphisms in FcepsilonRIbeta may be associated with the development of
      allergic diseases.

PMID- 29654164
TI  - Association of miRNA biosynthesis genes DROSHA and DGCR8 polymorphisms with
      cancer susceptibility: a systematic review and meta-analysis.
AB  - Single nucleotide polymorphisms (SNPs) in miRNA biosynthesis genes DROSHA and
      DGCR8 were indicated to be correlated with cancer risk. We comprehensively
      reviewed and analyzed the effect of DROSHA and DGCR8 polymorphisms on cancer
      risk. Eligible articles were selected according to a series of inclusion and
      exclusion criteria. Consequently, ten case-control studies (from nine citations)
      with 4265 cancer cases and 4349 controls were involved in a meta-analysis of
      seven most prevalent SNPs (rs10719 T/C, rs6877842 G/C, rs2291109 A/T, rs642321
      C/T, rs3757 G/A, rs417309 G/A, rs1640299 T/G). Our findings demonstrated that the
      rs417309 SNP in DGCR8 was significantly associated with an elevated risk of
      overall cancer in every genetic model. In stratified analysis, correlations of
      DROSHA rs10719 and rs6877842 SNPs were observed in Asian and laryngeal cancer
      subgroups, respectively. Moreover, associations of the rs417309 SNP could also be
      found in numerous subgroups including: Asian and Caucasian population subgroups;
      laryngeal and breast cancer subgroups; population-based (PB) and hospital-based
      (HB) subgroups. In conclusion, the DROSHA rs10719, rs6877842 SNPs, and DGCR8
      rs417309 SNP play pivotal roles in cancerogenesis and may be potential biomarkers
      for cancer-forewarning.

PMID- 29654159
TI  - Amyloid assembly and disassembly.
AB  - Amyloid fibrils are protein homopolymers that adopt diverse cross-beta
      conformations. Some amyloid fibrils are associated with the pathogenesis of
      devastating neurodegenerative disorders, including Alzheimer's disease and
      Parkinson's disease. Conversely, functional amyloids play beneficial roles in
      melanosome biogenesis, long-term memory formation and release of peptide
      hormones. Here, we showcase advances in our understanding of amyloid assembly and
      structure, and how distinct amyloid strains formed by the same protein can cause
      distinct neurodegenerative diseases. We discuss how mutant steric zippers promote
      deleterious amyloidogenesis and aberrant liquid-to-gel phase transitions. We also
      highlight effective strategies to combat amyloidogenesis and related toxicity,
      including: (1) small-molecule drugs (e.g. tafamidis) to inhibit amyloid formation
      or (2) stimulate amyloid degradation by the proteasome and autophagy, and (3)
      protein disaggregases that disassemble toxic amyloid and soluble oligomers. We
      anticipate that these advances will inspire therapeutics for several fatal
      neurodegenerative diseases.

PMID- 29654165
TI  - Knockdown of the oncogene lncRNA NEAT1 restores the availability of miR-34c and
      improves the sensitivity to cisplatin in osteosarcoma.
AB  - Aberrant expressions of long non-coding RNAs (lncRNAs) are the culprits of
      carcinogenesis via regulating the tumor suppressor or oncogene. LncRNA nuclear
      enriched abundant transcript 1 (NEAT1) has been identified to be an oncogene to
      promote tumor growth and metastasis of many cancers. However, the clinical
      significance and function of NEAT1 in osteosarcoma (OS) remain to be discovered.
      We here collected OS tissues (n=40) and adjacent non-tumor tissues (n=20) to
      determine the expression of NEAT1 and its clinical significance. NEAT1 was
      overexpressed in OS tissues, which positively correlated with tumor size,
      Enneking stage, and distant metastasis of OS patients. The elevated level of
      NEAT1 was confirmed in OS cell lines including MG63 and HOS in vitro Knockdown of
      NEAT1 by two siRNAs induced impaired cell vitalities, promoted the apoptosis, and
      G0/G1 arrest in two cell lines, which was associated with inhibited anti
      apoptosis signals BCL-2 pathway and cell cycle-related cyclin D1 (CCND1) signals.
      Moreover, the tumor suppressor miR-34c was negatively regulated and inhibited by
      NEAT1 in OS. Suppression of miR-34c could up-regulate the expressions of its
      target genes BCL-2 and CCND1 to antagonize the effects of NEAT1 knockdown.
      Furthermore, overexpressed NEAT1 reduced the sensitivity of cisplatin (DDP) and
      inhibited DDP-induced apoptosis and cell cycle arrest via miR-34c The results in
      vivo also confirmed that knockdown of NEAT1 sensitized the OS cells to DPP
      induced tumor regression, delayed the tumor growth with reduced levels of Ki-67,
      BCL-2, and cyclin D1 signals, suggesting that NEAT1 is an oncogene and
      chemotherapy resistant factor in OS.

PMID- 29654166
TI  - Pharmacological activation of AMPK and glucose uptake in cultured human skeletal
      muscle cells from patients with ME/CFS.
AB  - Skeletal muscle fatigue and post-exertional malaise are key symptoms of myalgic
      encephalomyelitis (ME)/chronic fatigue syndrome (ME/CFS). We have previously
      shown that AMP-activated protein kinase (AMPK) activation and glucose uptake are
      impaired in primary human skeletal muscle cell cultures derived from patients
      with ME/CFS in response to electrical pulse stimulation (EPS), a method which
      induces contraction of muscle cells in vitro The aim of the present study was to
      assess if AMPK could be activated pharmacologically in ME/CFS. Primary skeletal
      muscle cell cultures from patients with ME/CFS and healthy controls were treated
      with either metformin or compound 991. AMPK activation was assessed by Western
      blot and glucose uptake measured. Both metformin and 991 treatment significantly
      increased AMPK activation and glucose uptake in muscle cell cultures from both
      controls and ME/CFS. Cellular ATP content was unaffected by treatment although
      ATP content was significantly decreased in ME/CFS compared with controls.
      Pharmacological activation of AMPK can improve glucose uptake in muscle cell
      cultures from patients with ME/CFS. This suggests that the failure of EPS to
      activate AMPK in these muscle cultures is due to a defect proximal to AMPK.
      Further work is required to delineate the defect and determine whether
      pharmacological activation of AMPK improves muscle function in patients with
      ME/CFS.

PMID- 29654167
TI  - MiR-150-3p targets SP1 and suppresses the growth of glioma cells.
AB  - Glioma has been considered as one of the most prevalent and common malignancy of
      the nervous system; however, the underlying mechanisms that are responsible for
      the occurrence and development of glioma still remain largely unknown. Amounting
      evidence highlights the critical regulatory function of miRNAs in carcinogenesis.
      Here, we showed that the expression of miR-150-3p was significantly decreased in
      glioma tissues and cell lines. Suppressed expression of miR-150-3p was associated
      with the lymph node metastasis of the glioma patients. Overexpression of miR-150
      3p significantly inhibited the proliferation of glioma cells. Molecular study
      uncovered that the transcription factor specificity protein 1 (SP1) was
      identified as one of the targets of miR-150-3p Highly expressed miR-150-3p in
      glioma cells significantly decreased both the mRNA and protein levels of SP1.
      Consistently, the abundance of phosphatase and tension homolog deleted on
      chromosome ten (PTEN), a negative downstream target of SP1, was increased with
      the ectopic miR-150-3p Collectively, these results suggested that miR-150-3p
      suppressed the growth of glioma cells partially via regulating SP1 and possibly
      PTEN.

PMID- 29654168
TI  - Platelets in preeclamptic pregnancies fail to exhibit the decrease in
      mitochondrial oxygen consumption rate seen in normal pregnancies.
AB  - Cellular oxygen consumption and lactate production rates have been measured in
      both placental and myometrial cells to study obstetrics-related disease states
      such as preeclampsia. Platelet metabolic alterations indicate systemic
      bioenergetic changes that can be useful as disease biomarkers. We tested the
      hypothesis that platelet mitochondria display functional alterations in
      preeclampsia. Platelets were harvested from women in the third trimester of
      either a healthy, non-preeclamptic or preeclamptic pregnancy, and from healthy,
      non-pregnant women. Using Seahorse respirometry, we analyzed platelets for oxygen
      consumption (OCR) and extracellular acidification (ECAR) rates, indicators of
      mitochondrial electron transport and glucose metabolism, respectively. There was
      a 37% decrease in the maximal respiratory capacity measured in platelets from
      healthy, non-preeclamptic compared with preeclamptic pregnancy (P<0.01); this
      relationship held true for other measurements of OCR, including basal
      respiration; ATP-linked respiration; respiratory control ratio (RCR); and spare
      respiratory capacity. RCR, a measure of mitochondrial efficiency, was
      significantly lower in healthy pregnant compared with non-pregnant women. In
      contrast with increased OCR, basal ECAR was significantly reduced in platelets
      from preeclamptic pregnancies compared with either normal pregnancies (-25%;
      P<0.05) or non-pregnant women (-22%; P<0.01). Secondary analysis of OCR revealed
      reduced basal and maximal platelet respiration in normal pregnancy prior to 34
      weeks' estimated gestational age (EGA) compared with the non-pregnant state;
      these differences disappeared after 34 weeks. Taken together, findings suggest
      that in preeclampsia, there exists either a loss or early (before the third
      trimester) reversal of a normal biologic mechanism of platelet mitochondrial
      respiratory reduction associated with normal pregnancy.

PMID- 29654169
TI  - LncRNA AFAP1-AS1 is a prognostic biomarker and serves as oncogenic role in
      retinoblastoma.
AB  - The actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1) has been
      found to serve as an oncogenic long noncoding RNA (lncRNA) in most types of human
      cancer. The role of AFAP1-AS1 in retinoblastoma remains unknown. The purpose of
      the present study is to explore the clinical significance and biological function
      of AFAP1-AS1 in retinoblastoma. Levels of AFAP1-AS1 expression were measured in
      retinoblastoma tissues and cell lines. Loss-of-function study was performed to
      observe the effects of AFAP1-AS1 on retinoblastoma cell proliferation, cell
      cycle, migration, and invasion. In our results, AFAP1-AS1 expression was elevated
      in retinoblastoma tissues and cell lines, and associated with tumor size,
      choroidal invasion, and optic nerve invasion. Moreover, high expression of AFAP1
      AS1 was an independent unfavorable prognostic factor in retinoblastoma patients.
      The experiment in vitro suggested down-regulation of AFAP1-AS1 inhibited
      retinoblastoma cell proliferation, migration and invasion, and blocked cell
      cycle. In conclusion, AFAP1-AS1 functions as an oncogenic lncRNA in
      retinoblastoma.

PMID- 29654170
TI  - Association of the independent polymorphisms in CDKN2A with susceptibility of
      acute lymphoblastic leukemia.
AB  - Acute lymphoblastic leukemia (ALL) is the most common cancer in children, and
      alterations in CDKN2A were considered to play an important role on
      leukemogenesis. Two single nucleotide polymorphisms (SNPs) at CDKN2A locus were
      identified to impact on ALL susceptibility via genome wide association studies,
      and followed by multiple subsequent replication studies at the specific hits.
      Here, we conducted a systematic review and meta-analysis to re-evaluate the
      association of both SNPs (rs3731217 and rs3731249) with ALL susceptibility by
      gathering the data from 24 independent studies, totally containing 7922
      cases/21503 controls for rs3731217 and 6295 cases/24191 controls for rs3731249.
      Both SNPs were significantly associated with ALL risk (odds ratio [OR] = 0.72 and
      2.26 respectively), however, exhibit race-specific pattern. In summary, our meta
      analysis indicated that two SNPs at CDKN2A locus are associated with ALL
      susceptibility independently mainly in Caucasians. Future large-scale studies are
      required to validate the associations in other ethnicities.

PMID- 29654171
TI  - Meta-analysis of trimetazidine treatment for cardiomyopathy.
AB  - To explore the effect of trimetazidine (TMZ) in cardiomyopathy treatment.
      Literatures, related with TMZ treatment for cardiomyopathy, were retrieved
      between 1990 and February 2018 in the Pubmed, Embase, and Cochrane Library
      systems. Cardiopulmonary exercise testing [resting heart rate (RHR), peak heart
      rate (PHR), peak systolic blood pressure (PSBP), and resting systolic blood
      pressure (RSBP)] and echocardiographic results [left ventricular ejection
      fraction (LVEF), left ventricular end-systolic volume (LVESV), left ventricular
      end-diastolic volume (LVEDV), systolic wall thickening score index (SWTSI), left
      ventricular end-systolic diameter (LVESD), and left ventricular end-diastolic
      diameter (LVEDD)] were merged to detect the publication bias. Total 898 patients
      with cardiomyopathy were divided into two groups: TMZ-treated group (n=456) and
      control group (n=442). There was no difference in the improvement of
      cardiomyopathy between the TMZ and control group. No publication bias was shown
      for PHR (t= 0.9791, P=0.5067). There were significant differences in LVEF, LVESV,
      SWTSI, LVESD, and LVEDD between the TMZ group and the control group. TMZ
      treatment significantly increased the level of LVEF (95% confidence interval
      (CI): 5.46-7.84, P<0.001), and reduced the level of LVESV (95% CI: -18.73 to 
      7.77, P<0.001), SWTSI (95% CI: -0.47 to -0.15, Z = -3.85, P=0.001), LVESD (95%
      CI: -1.09 to -0.08, P<0.001), and LVEDD (95% CI: -0.55 to -0.26, P=0.023). There
      was no publication bias except for LVEDV (t = 2.5456, P=0.0438). TMZ is effective
      for cardiomyopathy treatment and worth to popularize in clinic.

PMID- 29654172
TI  - Genetic susceptibility of five tagSNPs in the endothelin-1 (EDN1) gene to
      coronary artery disease in a Chinese Han population.
AB  - Endothelin-1 (ET-1) plays important roles in endothelial dysfunction, vascular
      physiology, inflammation, and atherosclerosis. Nonetheless, the role of ET-1
      (EDN1) gene variants on coronary artery disease (CAD) risk remains poorly
      understood. The aim of the present study was to evaluate the role of EDN1 gene
      polymorphisms on individual susceptibility to CAD. We genotyped five tagSNPs
      (single-nucleotide polymorphisms) (rs6458155, rs4145451, rs9369217, rs3087459,
      and rs2070699) within EDN1 gene in 525 CAD patients and 675 control subjects. In
      a multivariate logistic regression analysis, we detected an association of
      rs6458155 in EDN1 gene with the CAD risk; compared with the TT homozygotes, the
      CT heterozygotes (odds ratio (OR) = 1.53, 95% confidence interval (CI) = 1.02
      2.29, P=0.040) and the CC homozygotes (OR = 1.55, 95% CI = 1.01-2.36, P=0.043)
      were statistically significantly associated with the increased risk for CAD. A
      similar trend of the association was found in dominant model (OR = 1.53, 95% CI =
      1.05-2.25, P=0.029). Consistently, the haplotype rs6458155C-rs4145451C containing
      rs6458155 C allele exhibited the increased CAD risk (OR = 1.22, 95% CI = 1.03
      1.43, and P=0.018). In addition, CT genotype of rs6458155 conferred the increased
      plasma ET-1 levels compared with TT genotype (P<0.05). No association of the
      other four tagSNPs in EDN1 gene with CAD risk was observed. In conclusion, our
      study provides the first evidence that EDN1 tagSNP rs6458155 is associated with
      CAD risk in the Chinese Han population, which is probably due to the influence of
      the circulating ET-1 levels.

PMID- 29654173
TI  - Evidence that the metabolite repair enzyme NAD(P)HX epimerase has a moonlighting
      function.
AB  - NAD(P)H-hydrate epimerase (EC 5.1.99.6) is known to help repair NAD(P)H hydrates
      (NAD(P)HX), which are damage products existing as R and S epimers. The S epimer
      is reconverted to NAD(P)H by a dehydratase; the epimerase facilitates epimer
      interconversion. Epimerase deficiency in humans causes a lethal disorder
      attributed to NADHX accumulation. However, bioinformatic evidence suggest caution
      about this attribution by predicting that the epimerase has a second function
      connected to vitamin B6 (pyridoxal 5'-phosphate and related compounds).
      Specifically, (i) the epimerase is fused to a B6 salvage enzyme in plants, (ii)
      epimerase genes cluster on the chromosome with B6-related genes in bacteria, and
      (iii) epimerase and B6-related genes are coexpressed in yeast and Arabidopsis The
      predicted second function was explored in Escherichia coli, whose epimerase and
      dehydratase are fused and encoded by yjeF The putative NAD(P)HX epimerase active
      site has a conserved lysine residue (K192 in E. coli YjeF). Changing this residue
      to alanine cut in vitro epimerase activity by >=95% but did not affect
      dehydratase activity. Mutant cells carrying the K192A mutation had essentially
      normal NAD(P)HX dehydratase activity and NAD(P)HX levels, showing that the
      mutation had little impact on NAD(P)HX repair in vivo However, these cells showed
      metabolome changes, particularly in amino acids, which exceeded those in cells
      lacking the entire yjeF gene. The K192A mutant cells also had reduced levels of
      'free' (i.e. weakly bound or unbound) pyridoxal 5'-phosphate. These results
      provide circumstantial evidence that the epimerase has a metabolic function
      beyond NAD(P)HX repair and that this function involves vitamin B6.

PMID- 29654174
TI  - Cezomycin Is Activated by CalC to Its Ester Form for Further Biosynthesis Steps
      in the Production of Calcimycin in Streptomyces chartreusis NRRL 3882.
AB  - Calcimycin, N-demethyl calcimycin, and cezomycin are polyether divalent cation
      ionophore secondary metabolites produced by Streptomyces chartreusis A thorough
      understanding of the organization of their encoding genes, biosynthetic
      pathway(s), and cation specificities is vitally important for their efficient
      future production and therapeutic use. So far, this has been lacking, as has
      information concerning any biosynthetic relationships that may exist between
      calcimycin and cezomycin. In this study, we observed that when a Cal- (calB1
      mutant) derivative of a calcimycin-producing strain of S. chartreusis (NRRL 3882)
      was grown on cezomycin, calcimycin production was restored. This suggested that
      calcimycin synthesis may have resulted from postsynthetic modification of
      cezomycin rather than from a de novo process through a novel and independent
      biosynthetic mechanism. Systematic screening of a number of Cal-S. chartreusis
      mutants lacking the ability to convert cezomycin to calcimycin allowed the
      identification of a gene, provisionally named calC, which was involved in the
      conversion step. Molecular cloning and heterologous expression of the CalC
      protein along with its purification to homogeneity and negative-staining electron
      microscopy allowed the determination of its apparent molecular weight, oligomeric
      forms in solution, and activity. These experiments allowed us to confirm that the
      protein possessed ATP pyrophosphatase activity and was capable of ligating
      coenzyme A (CoA) with cezomycin but not 3-hydroxyanthranilic acid. The CalC
      protein's apparent Km and kcat for cezomycin were observed to be 190 MUM and 3.98
      min-1, respectively, and it possessed the oligomeric form in solution. Our
      results unequivocally show that cezomycin is postsynthetically modified to
      calcimycin by the CalC protein through its activation of cezomycin to a CoA ester
      form.IMPORTANCE Calcimycin is a secondary metabolite divalent cation-ionophore
      that has been studied in the context of human health. However, detail is lacking
      with respect to both calcimycin's biosynthesis and its biochemical/biophysical
      properties as well as information regarding its, and its analogues', divalent
      cation binding specificities and other activities. Such knowledge would be useful
      in understanding how calcimycin and related compounds may be effective in
      modifying the calcium channel ion flux and might be useful in influencing the
      homeostasis of magnesium and manganese ions for the cure or control of human and
      bacterial infectious diseases. The results presented here unequivocally show that
      CalC protein is essential for the production of calcimycin, which is essentially
      a derivative of cezomycin, and allow us to propose a biosynthetic mechanism for
      calcimycin's production.

PMID- 29654175
TI  - Recycling of Overactivated Acyls by a Type II Thioesterase during Calcimycin
      Biosynthesis in Streptomyces chartreusis NRRL 3882.
AB  - Type II thioesterases typically function as editing enzymes, removing acyl groups
      that have been misconjugated to acyl carrier proteins during polyketide secondary
      metabolite biosynthesis as a consequence of biosynthetic errors. Streptomyces
      chartreusis NRRL 3882 produces the pyrrole polyether ionophoric antibiotic, and
      we have identified the presence of a putative type II thioesterase-like sequence,
      calG, within the biosynthetic gene cluster involved in the antibiotic's
      synthesis. However, targeted gene mutagenesis experiments in which calG was
      inactivated in the organism did not lead to a decrease in calcimycin production
      but rather reduced the strain's production of its biosynthetic precursor,
      cezomycin. Results from in vitro activity assays of purified, recombinant CalG
      protein indicated that it was involved in the hydrolysis of cezomycin coenzyme A
      (cezomycin-CoA), as well as other acyl CoAs, but was not active toward 3-S-N
      acetylcysteamine (SNAC; the mimic of the polyketide chain-releasing precursor).
      Further investigation of the enzyme's activity showed that it possessed a
      cezomycin-CoA hydrolysis Km of 0.67 mM and a kcat of 17.77 min-1 and was
      significantly inhibited by the presence of Mn2+ and Fe2+ divalent cations.
      Interestingly, when S. chartreusis NRRL 3882 was cultured in the presence of
      inorganic nitrite, NaNO2, it was observed that the production of calcimycin
      rather than cezomycin was promoted. Also, supplementation of S. chartreusis NRRL
      3882 growth medium with the divalent cations Ca2+, Mg2+, Mn2+, and Fe2+ had a
      similar effect. Taken together, these observations suggest that CalG is not
      responsible for megasynthase polyketide precursor chain release during the
      synthesis of calcimycin or for retaining the catalytic efficiency of the
      megasynthase enzyme complex as is supposed to be the function for type II
      thioesterases. Rather, our results suggest that CalG is a dedicated thioesterase
      that prevents the accumulation of cezomycin-CoA when intracellular nitrogen is
      limited, an apparently new and previously unreported function of type II
      thioesterases.IMPORTANCE Type II thioesterases (TEIIs) are generally regarded as
      being responsible for removing aberrant acyl groups that block polyketide
      production, thereby maintaining the efficiency of the megasynthase involved in
      this class of secondary metabolites' biosynthesis. Specifically, this class of
      enzyme is believed to be involved in editing misprimed precursors, controlling
      initial units, providing key intermediates, and releasing final synthetic
      products in the biosynthesis of this class of secondary metabolites. Our results
      indicate that the putative TEII CalG present in the calcimycin (A23187)-producing
      organism Streptomyces chartreusis NRRL 3882 is not important either for the
      retention of catalytic efficiency of, or for the release of the product compound
      from, the megasynthase involved in calcimycin biosynthesis. Rather, the enzyme is
      involved in regulating/controlling the pool size of the calcimycin biosynthetic
      precursor, cezomycin, by hydrolysis of its CoA derivative. This novel function of
      CalG suggests a possible additional activity for enzymes belonging to the TEII
      protein family and promotes better understanding of the overall biosynthetic
      mechanisms involved in the production of this class of secondary metabolites.

PMID- 29654176
TI  - Shewanella oneidensis MR-1 Utilizes both Sodium- and Proton-Pumping NADH
      Dehydrogenases during Aerobic Growth.
AB  - Shewanella oneidensis MR-1 is a metal-reducing bacterium with the ability to
      utilize many different terminal electron acceptors, including oxygen and solid
      metal oxides. Both metal oxide reduction and aerobic respiration have been
      studied extensively in this organism. However, electron transport chain processes
      upstream of the terminal oxidoreductases have been relatively understudied in
      this organism, especially electron transfer from NADH to respiratory quinones.
      Genome annotation indicates that S. oneidensis MR-1 encodes four NADH
      dehydrogenases, a proton-translocating dehydrogenase (Nuo), two sodium ion
      translocating dehydrogenases (Nqr1 and Nqr2), and an "uncoupling" dehydrogenase
      (Ndh), but none of these complexes have been studied. Therefore, we conducted a
      study specifically focused on the effects of individual NADH dehydrogenase
      knockouts in S. oneidensis MR-1. We observed that two of the single-mutant
      strains, the DeltanuoN and DeltanqrF1 mutants, exhibited significant growth
      defects compared with the wild type. However, the defects were minor and only
      apparent under certain growth conditions. Further testing of the DeltanuoN
      DeltanqrF1 double-mutant strain yielded no growth in minimal medium under oxic
      conditions, indicating that Nuo and Nqr1 have overlapping functions, but at least
      one is necessary for aerobic growth. Coutilization of proton- and sodium ion
      dependent energetics has important implications for the growth of this organism
      in environments with varied pH and salinity, including microbial electrochemical
      systems.IMPORTANCE Bacteria utilize a wide variety of metabolic pathways that
      allow them to take advantage of different energy sources, and to do so with
      varied efficiency. The efficiency of a metabolic process determines the growth
      yield of an organism, or the amount of biomass it produces per amount of
      substrate consumed. This parameter has important implications in biotechnology
      and wastewater treatment, where low growth yields are often preferred to minimize
      the production of microbial biomass. In this study, we investigated respiratory
      pathways containing NADH dehydrogenases with varied efficiency (i.e., the number
      of ions translocated per NADH oxidized) in the metal-reducing bacterium
      Shewanella oneidensis MR-1. We observed that two different respiratory pathways
      are used concurrently, and at least one pathway must be functional for growth
      under oxic conditions.

PMID- 29654177
TI  - Distinct Nitrite and Nitric Oxide Physiologies in Escherichia coli and Shewanella
      oneidensis.
AB  - Nitrite has been used as a bacteriostatic agent for centuries in food
      preservation. It is widely accepted that this biologically inert molecule
      functions indirectly, serving as a stable reservoir of bioactive nitric oxide
      (NO) and other reactive nitrogen species to impact physiology. As a result, to
      date, we know surprisingly little about in vivo targets of nitrite. Here, we
      carry out comparative analyses of nitrite and NO physiology in Escherichia coli
      and in Shewanella oneidensis, a Gram-negative environmental bacterium renowned
      for respiratory versatility. These two bacteria differ from each other in many
      aspects of nitrite and NO physiology, including NO generation, NO degradation,
      and unexpectedly, their contrary susceptibility to nitrite and NO. In cell
      extracts of both bacteria, most of the NO targets are also susceptible to
      nitrite, and vice versa. However, with respect to growth inhibition caused by NO,
      the targets are impacted distinctly; NO targets are responsible for the
      inhibition of growth of E. coli but not of S. oneidensis More surprisingly, all
      proteins identified to be implicated in NO tolerance in other bacteria appear to
      play a dispensable role in protecting S. oneidensis against NO. These data
      suggest that S. oneidensis is equipped with a robust but yet unknown NO
      protecting system. In the case of nitrite, it is clear that the target of
      physiological significance in both bacteria is cytochrome heme-copper
      oxidase.IMPORTANCE Nitrite is toxic to living organisms at high levels, but such
      antibacterial effects of nitrite are attributable to the formation of nitric
      oxide (NO), a highly reactive radical gas molecule. Here, we report that
      Shewanella oneidensis is highly resistant to NO but sensitive to nitrite compared
      to Escherichia coli by approximately 4-fold. In both bacteria, nitrite inhibits
      bacterial growth by targeting cytochrome heme-copper oxidase. In contrast, the
      targets of NO are diverse. Although these targets are similar in E. coli and S.
      oneidensis, they are responsible for growth inhibition caused by NO in the former
      but not in the latter. Overall, the presented data, along with the previous data,
      solidify a proposal that the in vivo targets of NO and nitrite in bacteria are
      largely different.

PMID- 29654178
TI  - Biosynthesis of Tropolones in Streptomyces spp: Interweaving Biosynthesis and
      Degradation of Phenylacetic Acid and Hydroxylations on Tropone Ring.
AB  - Tropolonoids are important natural products that contain a unique seven-membered
      aromatic tropolone core and exhibit remarkable biological activities. 3,7
      Dihydroxytropolone (DHT) isolated from Streptomyces species is a multiply
      hydroxylated tropolone exhibiting antimicrobial, anticancer, and antiviral
      activities. Herein, we determined the DHT biosynthetic pathway by heterologous
      expression, gene deletion, and bioconversion. Nine trl genes and some of the
      aerobic phenylacetic acid degradation pathway genes (paa) located outside of the
      trl biosynthetic gene cluster are required for the heterologous production of
      DHT. The trlA gene encodes a single-domain protein homologous to the C-terminal
      enoyl-CoA hydratase domain of PaaZ. TrlA truncates the phenylacetic acid
      catabolic pathway and redirects it towards the formation of heptacyclic
      intermediates. TrlB is a 3-deoxy-D-arabino-heptulosonic acid-7-phosphate (DAHP)
      synthase homolog. TrlH is an unusual bifunctional protein bearing an N-terminal
      prephenate dehydratase domain and a C-terminal chorismate mutase domain. TrlB and
      TrlH enhanced de novo biosynthesis of phenylpyruvate, thereby providing abundant
      precursor for the prolific production of DHT in Streptomyces Six seven-membered
      carbocyclic compounds were identified from the gene deletion mutants of trlC,
      trlD, trlE, and trlF Four of these chemicals, including 1,4,6-cycloheptatriene-1
      carboxylic acid, tropone, tropolone and 7-hydroxytropolone, were verified as key
      biosynthetic intermediates. TrlF is required for the conversion of 1,4,6
      cycloheptatriene-1-carboxylic acid into tropone. Monooxygenases TrlE and TrlCD
      catalyze the regioselective hydroxylations of tropone to afford DHT. This study
      reveals a natural association of anabolism of chorismate and phenylpyruvate,
      catabolism of phenylacetic acid, and biosynthesis of tropolones in Streptomyces
      spp.IMPORTANCETropolonoids are promising drug lead compounds because of their
      versatile bioactivities attributed to their highly oxidized seven-membered
      aromatic ring scaffolds. Our study here provides a clear insight into the
      biosynthesis of 3,7-dihydroxytropolone (DHT) through the identification of key
      genes responsible for the formation and modification of the seven-membered
      aromatic core. We also reveal the intrinsic mechanism of elevated production of
      DHT and related tropolonoids in Streptomyces spp. The study on DHT biosynthesis
      in Streptomyces exhibits a good example of antibiotic production in which both
      anabolic and catabolic pathways of primary metabolism are interwoven into the
      biosynthesis of secondary metabolites. Furthermore, our study sets the stage for
      metabolic engineering of tropolonoid natural products biosynthetic pathway and
      provides alternative synthetic biology tools for engineering novel tropolonoids.

PMID- 29654179
TI  - Uniform and Pitting Corrosion of Carbon Steel by Shewanella oneidensis MR-1 under
      Nitrate-Reducing Conditions.
AB  - Despite observations of steel corrosion in nitrate-reducing environments,
      processes of nitrate-dependent microbially influenced corrosion (MIC) remain
      poorly understood and difficult to identify. We evaluated carbon steel corrosion
      by Shewanella oneidensis MR-1 under nitrate-reducing conditions using a split
      chamber/zero-resistance ammetry (ZRA) technique. This approach entails the
      deployment of two metal (carbon steel 1018 in this case) electrodes into separate
      chambers of an electrochemical split-chamber unit, where the microbiology or
      chemistry of the chambers can be manipulated. This approach mimics the conditions
      of heterogeneous metal coverage that can lead to uniform and pitting corrosion.
      The current between working electrode 1 (WE1) and WE2 can be used to determine
      rates, mechanisms, and, we now show, extents of corrosion. When S. oneidensis was
      incubated in the WE1 chamber with lactate under nitrate-reducing conditions,
      nitrite transiently accumulated, and electron transfer from WE2 to WE1 occurred
      as long as nitrite was present. Nitrite in the WE1 chamber (without S.
      oneidensis) induced electron transfer in the same direction, indicating that
      nitrite cathodically protected WE1 and accelerated the corrosion of WE2. When S.
      oneidensis was incubated in the WE1 chamber without an electron donor, nitrate
      reduction proceeded, and electron transfer from WE2 to WE1 also occurred,
      indicating that the microorganism could use the carbon steel electrode as an
      electron donor for nitrate reduction. Our results indicate that under nitrate
      reducing conditions, uniform and pitting carbon steel corrosion can occur due to
      nitrite accumulation and the use of steel-Fe(0) as an electron donor, but
      conditions of sustained nitrite accumulation can lead to more-aggressive
      corrosive conditions.IMPORTANCE Microbially influenced corrosion (MIC) causes
      damage to metals and metal alloys that is estimated to cost over $100
      million/year in the United States for prevention, mitigation, and repair. While
      MIC occurs in a variety of settings and by a variety of organisms, the mechanisms
      by which microorganisms cause this damage remain unclear. Steel pipe and
      equipment may be exposed to nitrate, especially in oil and gas production, where
      this compound is used for corrosion and "souring" control. In this paper, we show
      uniform and pitting MIC under nitrate-reducing conditions and that a major
      mechanism by which it occurs is via the heterogeneous cathodic protection of
      metal surfaces by nitrite as well as by the microbial oxidation of steel-Fe(0).

PMID- 29654180
TI  - Carrot Juice Fermentations as Man-Made Microbial Ecosystems Dominated by Lactic
      Acid Bacteria.
AB  - Spontaneous vegetable fermentations, with their rich flavors and postulated
      health benefits, are regaining popularity. However, their microbiology is still
      poorly understood, therefore raising concerns about food safety. In addition,
      such spontaneous fermentations form interesting cases of man-made microbial
      ecosystems. Here, samples from 38 carrot juice fermentations were collected
      through a citizen science initiative, in addition to three laboratory
      fermentations. Culturing showed that Enterobacteriaceae were outcompeted by
      lactic acid bacteria (LAB) between 3 and 13 days of fermentation. Metabolite
      target analysis showed that lactic acid and mannitol were highly produced, as
      well as the biogenic amine cadaverine. High-throughput 16S rRNA gene sequencing
      revealed that mainly species of Leuconostoc and Lactobacillus (as identified by 8
      and 20 amplicon sequence variants [ASVs], respectively) mediated the
      fermentations in subsequent order. The analyses at the DNA level still detected a
      high number of Enterobacteriaceae, but their relative abundance was low when RNA
      based sequencing was performed to detect presumptive metabolically active
      bacterial cells. In addition, this method greatly reduced host read
      contamination. Phylogenetic placement indicated a high LAB diversity, with ASVs
      from nine different phylogenetic groups of the Lactobacillus genus complex.
      However, fermentation experiments with isolates showed that only strains
      belonging to the most prevalent phylogenetic groups preserved the fermentation
      dynamics. The carrot juice fermentation thus forms a robust man-made microbial
      ecosystem suitable for studies on LAB diversity and niche specificity.IMPORTANCE
      The usage of fermented food products by professional chefs is steadily growing
      worldwide. Meanwhile, this interest has also increased at the household level.
      However, many of these artisanal food products remain understudied. Here, an
      extensive microbial analysis was performed of spontaneous fermented carrot juices
      which are used as nonalcoholic alternatives for wine in a Belgian Michelin star
      restaurant. Samples were collected through an active citizen science approach
      with 38 participants, in addition to three laboratory fermentations.
      Identification of the main microbial players revealed that mainly species of
      Leuconostoc and Lactobacillus mediated the fermentations in subsequent order. In
      addition, a high diversity of lactic acid bacteria was found; however,
      fermentation experiments with isolates showed that only strains belonging to the
      most prevalent lactic acid bacteria preserved the fermentation dynamics. Finally,
      this study showed that the usage of RNA-based 16S rRNA amplicon sequencing
      greatly reduces host read contamination.

PMID- 29654181
TI  - Genomic and Transcriptomic Insights into How Bacteria Withstand High
      Concentrations of Benzalkonium Chloride Biocides.
AB  - Benzalkonium chlorides (BAC) are commonly used biocides in broad-spectrum
      disinfectant solutions. How microorganisms cope with BAC exposure remains poorly
      understood, despite its importance for disinfection and disinfectant-induced
      antibiotic resistance. To provide insights into these issues, we exposed two
      isolates of an opportunistic pathogen, Pseudomonas aeruginosa, to increasing
      concentrations of BAC. One isolate was preadapted to BAC, as it originated from a
      bioreactor fed with subinhibitory concentrations of BAC for 3 years, while the
      other originated from a bioreactor that received no BAC. Replicated populations
      of both isolates were able to survive high concentrations of BAC, up to 1,200 and
      1,600 mg/liter for the non- and preadapted strains, respectively, exceeding
      typical application doses. Transcriptome sequencing (RNA-seq) analysis revealed
      upregulation of efflux pump genes and decreased expression of porins related to
      BAC transport as well as reduced growth rate. Increased expression of spermidine
      (a polycation) synthase genes and mutations in the pmrB (polymyxin resistance)
      gene, which cause a reduction in membrane negative charge, suggested that a major
      adaptation to exposure to the cationic surfactant BAC was to actively stabilize
      cell surface charge. Collectively, these results revealed that P. aeruginosa
      adapts to BAC exposure by a combination of mechanisms and provided genetic
      markers to monitor BAC-resistant organisms that may have applications in the
      practice of disinfection.IMPORTANCE BAC are widely used as biocides in
      disinfectant solutions, food-processing lines, domestic households, and health
      care facilities. Due to their wide use and mode of action, there has been rising
      concern that BAC may promote antibiotic resistance. Consistent with this idea, at
      least 40 outbreaks have been attributed to infection by disinfectant- and
      antibiotic-resistant pathogens such as P. aeruginosa However, the underlying
      molecular mechanisms that bacteria use to deal with BAC exposure remain poorly
      elucidated. Elucidating these mechanisms may be important for monitoring and
      limiting the spread of disinfectant-resistant pathogens. Using an integrated
      approach that combined genomics and transcriptomics with physiological
      characterization of BAC-adapted isolates, this study provided a comprehensive
      understanding of the BAC resistance mechanisms in P. aeruginosa Our findings also
      revealed potential genetic markers to detect and monitor the abundance of BAC
      resistant pathogens across clinical or environmental settings. This work
      contributes new knowledge about high concentrations of benzalkonium chlorides
      disinfectants-resistance mechanisms at the whole-cell genomic and transcriptomic
      level.

PMID- 29654182
TI  - Cadmium Exposure-Sedum alfredii Planting Interactions Shape the Bacterial
      Community in the Hyperaccumulator Plant Rhizosphere.
AB  - Rhizospheric bacteria play important roles in plant tolerance and activation of
      heavy metals. Understanding the bacterial rhizobiome of hyperaccumulators may
      contribute to the development of optimized phytoextraction for metal-polluted
      soils. We used 16S rRNA gene amplicon sequencing to investigate the rhizospheric
      bacterial communities of the cadmium (Cd) hyperaccumulating ecotype (HE) Sedum
      alfredii in comparison to its nonhyperaccumulating ecotype (NHE). Both planting
      of two ecotypes of S. alfredii and elevated Cd levels significantly decreased
      bacterial alpha-diversity and altered bacterial community structure in soils. The
      HE rhizosphere harbored a unique bacterial community differing from those in its
      bulk soil and NHE counterparts. Several key taxa from Actinobacteria,
      Bacteroidetes, and TM7 were especially abundant in HE rhizospheres under high Cd
      stress. The actinobacterial genus Streptomyces was responsible for the majority
      of the divergence of bacterial community composition between the HE rhizosphere
      and other soil samples. In the HE rhizosphere, the abundance of Streptomyces was
      3.31- to 16.45-fold higher than that in other samples under high Cd stress. These
      results suggested that both the presence of the hyperaccumulator S. alfredii and
      Cd exposure select for a specialized rhizosphere bacterial community during
      phytoextraction of Cd-contaminated soils and that key taxa, such as the species
      affiliated with the genus Streptomyces, may play an important role in metal
      hyperaccumulation.IMPORTANCESedum alfredii is a well-known Cd hyperaccumulator
      native to China. Its potential for extracting Cd relies not only on its powerful
      uptake, translocation, and tolerance for Cd but also on processes underground
      (especially rhizosphere microbes) that facilitate root uptake and tolerance of
      the metal. In this study, a high-throughput sequencing approach was applied to
      gain insight into the soil-plant-microbe interactions that may influence Cd
      accumulation in the hyperaccumulator S. alfredii Here, we report the
      investigation of rhizosphere bacterial communities of S. alfredii in
      phytoremediation of different levels of Cd contamination in soils. Moreover, some
      key taxa in its rhizosphere identified in the study, such as the species
      affiliated with genus Streptomyces, may shed new light on the involvement of
      bacteria in phytoextraction of contaminated soils and provide new materials for
      phytoremediation optimization.

PMID- 29654183
TI  - Optimizing Recombinant Protein Production in the Escherichia coli Periplasm
      Alleviates Stress.
AB  - In Escherichia coli, many recombinant proteins are produced in the periplasm. To
      direct these proteins to this compartment, they are equipped with an N-terminal
      signal sequence so that they can traverse the cytoplasmic membrane via the
      protein-conducting Sec translocon. Recently, using the single-chain variable
      antibody fragment BL1, we have shown that harmonizing the target gene expression
      intensity with the Sec translocon capacity can be used to improve the production
      yields of a recombinant protein in the periplasm. Here, we have studied the
      consequences of improving the production of BL1 in the periplasm by using a
      proteomics approach. When the target gene expression intensity is not harmonized
      with the Sec translocon capacity, the impaired translocation of secretory
      proteins, protein misfolding/aggregation in the cytoplasm, and an inefficient
      energy metabolism result in poor growth and low protein production yields. The
      harmonization of the target gene expression intensity with the Sec translocon
      capacity results in normal growth, enhanced protein production yields, and,
      surprisingly, a composition of the proteome that is-besides the produced target
      the same as that of cells with an empty expression vector. Thus, the single-chain
      variable antibody fragment BL1 can be efficiently produced in the periplasm
      without causing any notable detrimental effects to the production host. Finally,
      we show that under the optimized conditions, a small fraction of the target
      protein is released into the extracellular milieu via outer membrane vesicles. We
      envisage that our observations can be used to design strategies to further
      improve the production of secretory recombinant proteins in E. coliIMPORTANCE The
      bacterium Escherichia coli is widely used to produce recombinant proteins.
      Usually, trial-and-error-based screening approaches are used to identify
      conditions that lead to high recombinant protein production yields. Here, for the
      production of an antibody fragment in the periplasm of E. coli, we show that an
      optimization of its production is accompanied by the alleviation of stress. This
      indicates that the monitoring of stress responses could be used to facilitate
      enhanced recombinant protein production yields.

PMID- 29654184
TI  - Changes in the Rumen Epithelial Microbiota of Cattle and Host Gene Expression in
      Response to Alterations in Dietary Carbohydrate Composition.
AB  - The inclusion of high-quality hay (HQH), in place of concentrates, shifts dietary
      carbohydrate intake, and the extent to which these shifts effect epimural
      microbiota and epithelial gene expression of the rumen has not yet been
      evaluated. Eight ruminally cannulated nonlactating Holstein cows were used in a
      replicated 4 by 4 Latin square design with four dietary treatments containing
      HQH, with either 0% concentrate/100% HQH (100HQH), 25% concentrate/75% HQH
      (75HQH), or 40% concentrate/60% HQH (60HQH). The fourth group (control [CON]) was
      fed 60% normal fiber-rich hay and 40% concentrate. The data showed that measures
      of diversity for the rumen epimural population, specifically the Shannon (P =
      0.004) and Simpson (P = 0.003) indices, decreased with increasing levels of HQH
      in the diet. The feeding of HQH shifted the epimural population from
      predominantly Firmicutes to Proteobacteria Phylogenetic analysis revealed that
      HQH feeding markedly shifted the abundance of Campylobacter spp. from 7.8 up to
      33.5% (P < 0.001), with greater ingestion of protein (r = 0.63) and sugars (r =
      0.65) in HQH diet being responsible for this shift. The expression of genes
      targeting intracellular pH regulation, barrier function, and nutrient uptake of
      rumen epithelium remained stable regardless of the carbohydrate source. In
      conclusion, the data suggest strong alterations of the ruminal epimural
      microbiota in response to changes in the nutritive patterns of the diet. Further
      research is warranted to evaluate the long-term effects of these significant
      microbial changes on rumen health and food safety aspects in cattle at a
      transcriptional level.IMPORTANCE Feeding of forages versus starchy concentrates
      is a highly debated topic. Hay is believed to be healthier and more ecological
      sustainable for cattle than are concentrates, although the effects of feeding hay
      with enhanced sugar and protein content on epimural microbiota and host gene
      expression have not yet been evaluated. This research provides a report of the
      role of feeding hay with increased sugar and protein content in place of starchy
      concentrates in altering epimural microbiota and in generating a host response.
      Our research shows that the addition of high-quality hay to dairy rations shifted
      nutrient intake, resulting in strong alterations in the epimural microbiota in
      cattle. This work provides a background for further long-term research regarding
      the effects of feeding practices on the host-microbiome interaction and its role
      in rumen health and food safety in cattle.

PMID- 29654185
TI  - Redefinition and Unification of the SXT/R391 Family of Integrative and
      Conjugative Elements.
AB  - Integrative and conjugative elements (ICEs) of the SXT/R391 family are key
      drivers of the spread of antibiotic resistance in Vibrio cholerae, the infectious
      agent of cholera, and other pathogenic bacteria. The SXT/R391 family of ICEs was
      defined based on the conservation of a core set of 52 genes and site-specific
      integration into the 5' end of the chromosomal gene prfC Hence, the integrase
      gene int has been intensively used as a marker to detect SXT/R391 ICEs in
      clinical isolates. ICEs sharing most core genes but differing by their
      integration site and integrase gene have been recently reported and excluded from
      the SXT/R391 family. Here we explored the prevalence and diversity of atypical
      ICEs in GenBank databases and their relationship with typical SXT/R391 ICEs. We
      found atypical ICEs in V. cholerae isolates that predate the emergence and
      expansion of typical SXT/R391 ICEs in the mid-1980s in seventh-pandemic toxigenic
      V. cholerae strains O1 and O139. Our analyses revealed that while atypical ICEs
      are not associated with antibiotic resistance genes, they often carry cation
      efflux pumps, suggesting heavy metal resistance. Atypical ICEs constitute a
      polyphyletic group likely because of occasional recombination events with typical
      ICEs. Furthermore, we show that the alternative integration and excision genes of
      atypical ICEs remain under the control of SetCD, the main activator of the
      conjugative functions of SXT/R391 ICEs. Together, these observations indicate
      that substitution of the integration/excision module and change of specificity of
      integration do not preclude atypical ICEs from inclusion into the SXT/R391
      family.IMPORTANCEVibrio cholerae is the causative agent of cholera, an acute
      intestinal infection that remains to this day a world public health threat.
      Integrative and conjugative elements (ICEs) of the SXT/R391 family have played a
      major role in spreading antimicrobial resistance in seventh-pandemic V. cholerae
      but also in several species of Enterobacteriaceae Most epidemiological surveys
      use the integrase gene as a marker to screen for SXT/R391 ICEs in clinical or
      environmental strains. With the recent reports of closely related elements that
      carry an alternative integrase gene, it became urgent to investigate whether ICEs
      that have been left out of the family are a liability for the accuracy of such
      screenings. In this study, based on comparative genomics, we broaden the SXT/R391
      family of ICEs to include atypical ICEs that are often associated with heavy
      metal resistance.

PMID- 29654186
TI  - A Standard Method to Inactivate Bacillus anthracis Spores to Sterility Using
      gamma-Irradiation.
AB  - In 2015, a laboratory of the United States Department of Defense (DoD)
      inadvertently shipped preparations of gamma-irradiated spores of Bacillus
      anthracis that contained live spores. In response, a systematic, evidence-based
      method for preparing, concentrating, irradiating, and verifying inactivation of
      spore materials was developed. We demonstrate consistency of spore preparations
      across multiple biological replicates and show that two different DoD
      institutions arrive independently at comparable dose-inactivation curves for a
      monodisperse suspension of B. anthracis spores containing 3 * 1010 colony forming
      units (CFU). Spore preparations from three different institutions in three strain
      backgrounds yielded similar decimal-reduction (D10) values and irradiation doses
      required to assure sterility (DSAL) to the point at which the probability of
      detecting a viable spore is 10-6 Furthermore, spores of a genetically-tagged
      strain of B. anthracis Sterne were used to show that high densities of dead
      spores suppress the recovery of viable spores. Together, we present an integrated
      method for preparing, irradiating, and verifying the inactivation of spores of B.
      anthracis for use as standard reagents for testing and evaluating detection and
      diagnostic devices and techniques.Importance: The inadvertent shipment by a U.S.
      Department of Defense (DoD) laboratory of live Bacillus anthracis (anthrax)
      spores to U.S. and international destinations revealed the need to standardize
      inactivation methods for materials derived from Biological Select Agents and
      Toxins (BSAT) and for the development of evidence-based methods to prevent the
      recurrence of such an event. Following a retrospective analysis of the procedures
      previously employed to generate inactivated B. anthracis spores, a study was
      commissioned by the DoD to provide the data required to support the production of
      inactivated spores for the biodefense community. The results of this work are
      presented in this publication, which details the method by which spores can be
      prepared, irradiated and tested such that the chance of finding residual living
      spores in any given preparation is 1/1,000,000. These irradiated spores are used
      to test equipment and methods for detection of agents of biological warfare and
      bioterrorism.

PMID- 29654188
TI  - Mirror Neuron Populations Represent Sequences of Behavioral Epochs During Both
      Execution and Observation.
AB  - Mirror neurons (MNs) have the distinguishing characteristic of modulating during
      both execution and observation of an action. Although most studies of MNs have
      focused on various features of the observed movement, MNs also may monitor the
      behavioral circumstances in which the movement is embedded, including time
      periods preceding and following the observed movement. Here, we recorded multiple
      MNs simultaneously from implanted electrode arrays as two male monkeys executed
      and observed a reach, grasp, and manipulate task involving different target
      objects. MNs were recorded from premotor cortex (PM-MNs) and primary motor cortex
      (M1-MNs). During execution trials, hidden Markov models (HMMs) applied to the
      activity of either PM-MN or M1-MN populations most often detected sequences of
      four hidden states, which we named according to the behavioral epoch during which
      each state began: initial, reaction, movement, and final. The hidden states of MN
      populations thus reflected not only the movement, but also three behavioral
      epochs during which no movement occurred. HMMs trained on execution trials could
      decode similar sequences of hidden states in observation trials, with complete
      hidden state sequences decoded more frequently from PM-MN populations than from
      M1-MN populations. Moreover, population trajectories projected in a 2D plane
      defined by execution trials were preserved in observation trials more for PM-MN
      than for M1-MN populations. These results suggest that MN populations represent
      entire behavioral sequences, including both movement and non-movement. PM-MN
      populations showed greater similarity than M1-MN populations in their
      representation of behavioral sequences during execution versus
      observation.SIGNIFICANCE STATEMENT Mirror neurons (MNs) are thought to provide a
      neural mechanism for understanding the actions of others. However, for an action
      to be understood, both the movement per se and the non-movement context before
      and after the movement need to be represented. We found that simultaneously
      recorded MN populations encoded sequential hidden neural states corresponding
      approximately to sequential behavioral epochs of a reach, grasp, and manipulate
      task. During observation trials, hidden state sequences were similar to those
      identified in execution trials. Hidden state similarity was stronger for MN
      populations in premotor cortex than for those in primary motor cortex.
      Execution/observation similarity of hidden state sequences may contribute to
      understanding the actions of others without actually performing the action
      oneself.

PMID- 29654189
TI  - Restoring Tip60 HAT/HDAC2 Balance in the Neurodegenerative Brain Relieves
      Epigenetic Transcriptional Repression and Reinstates Cognition.
AB  - Cognitive decline is a debilitating hallmark during preclinical stages of
      Alzheimer's disease (AD), yet the causes remain unclear. Because histone
      acetylation homeostasis is critical for mediating epigenetic gene control
      throughout neuronal development, we postulated that its misregulation contributes
      to cognitive impairment preceding AD pathology. Here, we show that disruption of
      Tip60 histone acetlytransferase (HAT)/histone deacetylase 2 (HDAC2) homeostasis
      occurs early in the brain of an AD-associated amyloid precursor protein (APP)
      Drosophila model and triggers epigenetic repression of neuroplasticity genes well
      before Abeta plaques form in male and female larvae. Repressed genes display
      enhanced HDAC2 binding and reduced Tip60 and histone acetylation enrichment.
      Increasing Tip60 in the AD-associated APP brain restores Tip60 HAT/HDAC2 balance
      by decreasing HDAC2 levels, reverses neuroepigenetic alterations to activate
      synaptic plasticity genes, and reinstates brain morphology and cognition. Such
      Drosophila neuroplasticity gene epigenetic signatures are conserved in male and
      female mouse hippocampus and their expression and Tip60 function is compromised
      in hippocampus from AD patients. We suggest that Tip60 HAT/HDAC2-mediated
      epigenetic gene disruption is a critical initial step in AD that is reversed by
      restoring Tip60 in the brain.SIGNIFICANCE STATEMENT Mild cognitive impairment is
      a debilitating hallmark during preclinical stages of Alzheimer's disease (AD),
      yet its causes remain unclear. Although recent findings support elevated histone
      deacetylase 2 (HDAC2) as a cause for epigenetic repression of synaptic genes that
      contribute to cognitive deficits, whether alterations in histone
      acetlytransferase (HAT) levels that counterbalance HDAC2 repressor action occur
      and the identity of these HATs remain unknown. We demonstrate that disruption of
      Tip60 HAT/HDAC2 homeostasis occurs early in the AD Drosophila brain and triggers
      epigenetic repression of neuroplasticity genes before Abeta plaques form.
      Increasing Tip60 in the AD brain restores Tip60 HAT/HDAC2 balance, reverses
      neuroepigenetic alterations to activate synaptic genes, and reinstates brain
      morphology and cognition. Our data suggest that disruption of the Tip60 HAT/HDAC2
      balance is a critical initial step in AD.

PMID- 29654190
TI  - Control of Excitation/Inhibition Balance in a Hippocampal Circuit by Calcium
      Sensor Protein Regulation of Presynaptic Calcium Channels.
AB  - Activity-dependent regulation controls the balance of synaptic excitation to
      inhibition in neural circuits, and disruption of this regulation impairs learning
      and memory and causes many neurological disorders. The molecular mechanisms
      underlying short-term synaptic plasticity are incompletely understood, and their
      role in inhibitory synapses remains uncertain. Here we show that regulation of
      voltage-gated calcium (Ca2+) channel type 2.1 (CaV2.1) by neuronal Ca2+ sensor
      (CaS) proteins controls synaptic plasticity and excitation/inhibition balance in
      a hippocampal circuit. Prevention of CaS protein regulation by introducing the IM
      AA mutation in CaV2.1 channels in male and female mice impairs short-term
      synaptic facilitation at excitatory synapses of CA3 pyramidal neurons onto
      parvalbumin (PV)-expressing basket cells. In sharp contrast, the IM-AA mutation
      abolishes rapid synaptic depression in the inhibitory synapses of PV basket cells
      onto CA1 pyramidal neurons. These results show that CaS protein regulation of
      facilitation and inactivation of CaV2.1 channels controls the direction of short
      term plasticity at these two synapses. Deletion of the CaS protein
      CaBP1/caldendrin also blocks rapid depression at PV-CA1 synapses, implicating its
      upregulation of inactivation of CaV2.1 channels in control of short-term synaptic
      plasticity at this inhibitory synapse. Studies of local-circuit function revealed
      reduced inhibition of CA1 pyramidal neurons by the disynaptic pathway from CA3
      pyramidal cells via PV basket cells and greatly increased excitation/inhibition
      ratio of the direct excitatory input versus indirect inhibitory input from CA3
      pyramidal neurons to CA1 pyramidal neurons. This striking defect in local-circuit
      function may contribute to the dramatic impairment of spatial learning and memory
      in IM-AA mice.SIGNIFICANCE STATEMENT Many forms of short-term synaptic plasticity
      in neuronal circuits rely on regulation of presynaptic voltage-gated Ca2+ (CaV)
      channels. Regulation of CaV2.1 channels by neuronal calcium sensor (CaS) proteins
      controls short-term synaptic plasticity. Here we demonstrate a direct link
      between regulation of CaV2.1 channels and short-term synaptic plasticity in
      native hippocampal excitatory and inhibitory synapses. We also identify
      CaBP1/caldendrin as the calcium sensor interacting with CaV2.1 channels to
      mediate rapid synaptic depression in the inhibitory hippocampal synapses of
      parvalbumin-expressing basket cells to CA1 pyramidal cells. Disruption of this
      regulation causes altered short-term plasticity and impaired balance of
      hippocampal excitatory to inhibitory circuits.

PMID- 29654191
TI  - Predictors of Mortality and Symptomatic Outcome of Patients With Low-Flow Severe
      Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement.
AB  - BACKGROUND: Impaired left ventricular (LV) ejection fraction is a common finding
      in patients with aortic stenosis and serves as a predictor of morbidity and
      mortality after transcatheter aortic valve replacement. However, conflicting data
      on the most accurate measure for LV function exist. We wanted to examine the
      impact of LV ejection fraction, mean pressure gradient, and stroke volume index
      on the outcome of patients treated by transcatheter aortic valve replacement.
      METHODS AND RESULTS: Patients treated by transcatheter aortic valve replacement
      were primarily separated into normal flow (NF; stroke volume index >35 mL/m2) and
      low flow (LF; stroke volume index <=35 mL/m2). Afterwards, patients were divided
      into 5 groups: "NF-high gradient," "NF-low gradient" (NF-LG), "LF-high gradient,"
      "paradoxical LF-LG," and "classic LF-LG." The 3-year mortality was the primary
      end point. Of 1600 patients, 789 (49.3%) were diagnosed as having LF, which was
      characterized by a higher 30-day (P=0.041) and 3-year (P<0.001) mortality. LF was
      an independent predictor of all-cause (hazard ratio, 1.29; 95% confidence
      interval, 1.03-1.62; P=0.03) and cardiovascular (hazard ratio, 1.37; 95%
      confidence interval, 1.06-1.77; P=0.016) mortality. Neither mean pressure
      gradient nor LV ejection fraction was an independent predictor of mortality.
      Patients with paradoxical LF-LG (35.0%), classic LF-LG (35.1%) and LF-high
      gradient (38.1%) had higher all-cause mortality at 3 years compared with NF-high
      gradient (24.8%) and NF-LG (27.9%) (P=0.001). However, surviving patients showed
      a similar improvement in symptoms regardless of aortic stenosis entity.
      CONCLUSIONS: LF is a common finding within the aortic stenosis population and, in
      contrast to LV ejection fraction or mean pressure gradient, an independent
      predictor of all-cause and cardiovascular mortality. Despite increased long-term
      mortality, high procedural success and excellent functional improvement support
      transcatheter aortic valve replacement in patients with LF severe aortic
      stenosis.

PMID- 29654192
TI  - Social Network Trajectories in Myocardial Infarction Versus Ischemic Stroke.
AB  - BACKGROUND: Changes in social networks are rarely examined before and after
      various diseases because of insufficient data. CHS (The Cardiovascular Health
      Study) offers an opportunity to compare social network trajectories surrounding
      well-adjudicated myocardial infarction (MI) or stroke events. We tested the
      hypothesis that social networks will be stable after MI and decrease after
      stroke. METHODS AND RESULTS: We examined trajectories of the Lubben Social
      Network Scale score (LSNS, range 0-50) before and after vascular events over 11
      years. The LSNS assesses engagement in family networks, friends' networks, and
      social supports. We used a linear mixed model with repeated measures and fixed
      effects to compare the change in social network score before and after events in
      395 people with MI and 382 with ischemic stroke. Over a mean of 12.4 years of
      follow-up for MI and 11.1 years for stroke, we examined an average of 4 social
      network scores for each participant. We controlled for sociodemographics,
      baseline cognitive function, and comorbidities. The participants' mean age was
      73.5, 51% were women, and 88% were non-Hispanic white. After MI, the social
      network trajectory remained stable compared with the baseline trajectory (-0.06
      points per year, adjusted P=0.2356). After stroke, the social network trajectory
      declined compared with the baseline trajectory (-0.14 points per year, adjusted
      P=0.0364). CONCLUSIONS: Social networks remained stable after MI and declined
      after stroke. This small and persistent decline after adjustment for potential
      confounders is notable because it deviates from stable network trajectories found
      in CHS participants and is specific to stroke.

PMID- 29654193
TI  - Hypertriglyceridemic Waist: A Simple Marker of High-Risk Atherosclerosis Features
      Associated With Excess Visceral Adiposity/Ectopic Fat.
AB  - BACKGROUND: Subclinical atherosclerosis identification remains challenging;
      abdominal visceral adiposity may improve risk stratification beyond traditional
      cardiovascular risk factors. Hypertriglyceridemic waist, a visceral adiposity
      marker combining elevated triglycerides (>=2 mmol/L) and waist circumference
      (>=90 cm), has been related to carotid atherosclerosis, although associations
      with high-risk features, including lipid-rich necrotic core (LRNC), remain
      unknown. We tested the hypothesis that hypertriglyceridemic waist is an
      independent marker of high-risk atherosclerosis features. METHODS AND RESULTS: In
      this cross-sectional study including 467 white men (mean age, 45.9+/-14.8 years;
      range 19.4-77.6 years), carotid atherosclerosis characteristics were examined by
      magnetic resonance imaging and associations with hypertriglyceridemic waist and
      benefits beyond Framingham Risk Score (FRS) and Pathobiological Determinants of
      Atherosclerosis in Youth (PDAY) were determined. Subclinical carotid
      atherosclerosis was present in 61.9% of participants, whereas 50.1% had LRNC.
      Hypertriglyceridemic waist was associated with carotid maximum wall thickness
      (P=0.014), wall volume (P=0.025), normalized wall index (P=0.004), and Carotid
      Atherosclerosis Score (derived from wall thickness and LRNC; P=0.049).
      Hypertriglyceridemic waist was associated with carotid LRNC volume beyond FRS
      (P=0.037) or PDAY (P=0.015), contrary to waist circumference alone (both P>0.05).
      Although 69.7% and 62.0% of participants with carotid atherosclerosis and/or LRNC
      were not high-risk by FRS or PDAY, respectively, hypertriglyceridemic waist
      correctly reclassified 9.7% and 4.5% of them, respectively. Combining
      hypertriglyceridemic waist with FRS (net reclassification improvement=0.17;
      P<0.001) or PDAY (net reclassification improvement=0.05; P=0.003) was superior to
      each score alone in identifying individuals with carotid atherosclerosis and/or
      LRNC. CONCLUSIONS: Hypertriglyceridemic waist is an independent marker of carotid
      high-risk atherosclerosis features in men, improving on FRS and PDAY risk score.

PMID- 29654194
TI  - Specific Pharmacological Profile of A2A Adenosine Receptor Predicts Reduced
      Fractional Flow Reserve in Patients With Suspected Coronary Artery Disease.
AB  - BACKGROUND: The rapid and reliable exclusion of myocardial revascularization is a
      major unmet clinical need in patients with suspected coronary artery disease
      (CAD) and non-contributive electrocardiography and troponin. Non-invasive tests
      have high rates of false positives and negatives, and there is no biomarker to
      assess myocardial ischemia. The presence of spare adenosine A2A receptors (A2AR)
      characterized by a high dissociation constant/half maximal effective
      concentration (KD/EC50) ratio-expressed on peripheral blood mononuclear cells
      (PBMC) has been associated with ischemia during exercise stress testing in
      patients with CAD. In this work, we investigated the diagnostic accuracy of spare
      A2AR versus fractional flow reserve (FFR) in patients with suspected CAD. METHODS
      AND RESULTS: Sixty patients with suspected CAD, but non-contributive
      electrocardiography and troponin, were consecutively enrolled in this prospective
      study. The binding (KD), functional response (cyclic adenosine monophosphate
      [cAMP] production; EC50) on PBMC A2AR were compared with FFR results. Patients
      were divided into 3 groups: 17 (group 1) with normal coronary angiography (n=13)
      or stenosis <20% (n=4); 21 with CAD and non-significant FFR (group 2); and 22
      with CAD and significant FFR (group 3). Median KD/EC50 was 6-fold higher in group
      3 (4.20; interquartile range: 2.81-5.00) than group 2 (0.66; interquartile range:
      0.47-1.25) and 7-fold higher than group 1 (0.60; interquartile range: 0.30-0.66).
      CONCLUSIONS: In patients with suspected CAD and non-contributive
      electrocardiography and troponin, the absence of spare A2AR on PBMC may help to
      rule out myocardial ischemia. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT03218007.

PMID- 29654195
TI  - Extravascular Blood Augments Myogenic Constriction of Cerebral Arterioles:
      Implications for Hemorrhage-Induced Vasospasm.
AB  - BACKGROUND: Subarachnoid hemorrhage is a serious clinical condition that impairs
      local cerebral blood flow perfusion and consequently initiates neuronal
      dysfunction. Pressure-sensitive myogenic vasomotor regulation is an important
      mechanism involved in the regulation of cerebral blood flow. We hypothesized that
      extravascular hemolyzed blood enhances arteriolar myogenic constriction, which in
      vivo may contribute to the reduction of local cerebral blood flow after
      subarachnoid hemorrhage. METHODS AND RESULTS: Arterioles isolated from the middle
      cerebral artery (MCA arterioles) of mice were cannulated in a perfusion chamber.
      Arteriolar diameters in response to step increases in intraluminal pressure (20
      120 mm Hg) were measured in various experimental conditions. In response to
      increases in intraluminal pressure, all MCA arterioles exhibited myogenic
      vasoconstrictions. Compared with controls, the pressure-induced constriction was
      significantly enhanced in arterioles (in vitro) exposed to extravascular
      hemolyzed blood or different concentrations of extracellular erythrocyte lysate
      (1%, 10%, and 20%) for different exposure durations (1-6 hours). The magnitude of
      enhancement was proportional to the lysate concentration and exposure duration.
      In in vivo experiments, 10 MUL of autologous blood lysate were injected into the
      mouse subarachnoid space on the surface of the left MCA. Two hours later, MCA
      arterioles were isolated and left MCA arterioles displayed enhanced myogenic
      responses compared with the right MCA. The enhanced myogenic response was
      prevented by scavenge of superoxide in both in vitro and in vivo experiments.
      CONCLUSIONS: Extravascular hemolyzed blood, perhaps by promoting vascular
      production of superoxide, augments myogenic constriction of cerebral arterioles,
      which plays a crucial role in the subarachnoid hemorrhage-induced cerebral
      ischemia.

PMID- 29654196
TI  - Effectiveness and Safety of Apixaban, Dabigatran, and Rivaroxaban Versus Warfarin
      in Frail Patients With Nonvalvular Atrial Fibrillation.
AB  - BACKGROUND: Frailty predicts poorer outcomes and decreased anticoagulation use in
      patients with nonvalvular atrial fibrillation. We sought to assess the
      effectiveness and safety of apixaban, dabigatran and rivaroxaban versus warfarin
      in frail nonvalvular atrial fibrillation patients. METHODS AND RESULTS: Using US
      MarketScan claims data from November 2011 to December 2016, we identified frail
      oral anticoagulant-naive nonvalvular atrial fibrillation patients with >=12
      months of continuous insurance coverage before oral anticoagulant initiation.
      Frailty status was determined using the Johns Hopkins Claims-based Frailty
      Indicator score (>=0.20 indicating frailty). Users of apixaban, dabigatran, or
      rivaroxaban were separately 1:1 matched to warfarin users via propensity-scores,
      with residual absolute standardized differences <0.1 being achieved for all
      covariates after matching. Patients were followed for up to 2 years or until an
      event, insurance disenrollment or end of follow-up. Rates of stroke or systemic
      embolism and major bleeding were compared using Cox regression and reported as
      hazard ratios (HRs) and 95% confidence intervals (CIs). In total, 2700, 2784, and
      5270 patients were included in the apixaban, dabigatran, and rivaroxaban 1:1
      matched analyses to warfarin. At 2 years, neither apixaban nor dabigatran were
      associated with differences in the hazard of stroke or systemic embolism
      (HR=0.78; 95% CI=0.46-1.35 and HR=0.94; 0.60-1.45) or major bleeding (HR=0.72;
      95% CI=0.49-1.06 and HR=0.87; 95% CI=0.63-1.19) versus warfarin. Rivaroxaban was
      associated with reduced stroke or systemic embolism at 2 years (HR=0.68; 95%
      CI=0.49-0.95) without significantly altering major bleeding risk (HR=1.07; 95%
      CI=0.81-1.32). CONCLUSIONS: Our study found rivaroxaban but not apixaban or
      dabigatran to be associated with reduced SSE versus warfarin in frail nonvalvular
      atrial fibrillation patients. No direct-acting oral anticoagulants demonstrated a
      significant difference in major bleeding versus warfarin.

PMID- 29654197
TI  - Serum Magnesium Levels and Outcomes in Patients With Acute Spontaneous
      Intracerebral Hemorrhage.
AB  - BACKGROUND: Magnesium (Mg) has potential hemostatic properties. We sought to
      investigate the potential association of serum Mg levels (at baseline and at 48
      hours) with outcomes in patients with acute spontaneous intracerebral hemorrhage
      (ICH). METHODS AND RESULTS: We reviewed data on all patients with spontaneous ICH
      with available Mg levels at baseline, over a 5-year period. Clinical and
      radiological outcome measures included initial hematoma volume, admission
      National Institutes of Health Stroke Scale and ICH scores, in-hospital mortality,
      favorable functional outcome (modified Rankin Scale scores, 0-1), and functional
      independence (modified Rankin Scale scores, 0-2) at discharge. Our study
      population consisted of 299 patients with ICH (mean age, 61+/-13 years; mean
      admission serum Mg, 1.8+/-0.3 mg/dL). Increasing admission Mg levels strongly
      correlated with lower admission National Institutes of Health Stroke Scale score
      (Spearman's r, -0.141; P=0.015), lower ICH score (Spearman's r, -0.153; P=0.009),
      and lower initial hematoma volume (Spearman's r, -0.153; P=0.012). Higher
      admission Mg levels were documented in patients with favorable functional outcome
      (1.9+/-0.3 versus 1.8+/-0.3 mg/dL; P=0.025) and functional independence (1.9+/
      0.3 versus 1.8+/-0.3 mg/dL; P=0.022) at discharge. No association between serum
      Mg levels at 48 hours and any of the outcome variables was detected. In multiple
      linear regression analyses, a 0.1-mg/dL increase in admission serum Mg was
      independently and negatively associated with the cubed root of hematoma volume at
      admission (regression coefficient, -0.020; 95% confidence interval, -0.040 to 
      0.000; P=0.049) and admission ICH score (regression coefficient, -0.053; 95%
      confidence interval, -0.102 to -0.005; P=0.032). CONCLUSIONS: Higher admission Mg
      levels were independently related to lower admission hematoma volume and lower
      admission ICH score in patients with acute spontaneous ICH.

PMID- 29654198
TI  - Examining the Use of a Social Media Campaign to Increase Engagement for the
      American Heart Association 2017 Resuscitation Science Symposium.
AB  - BACKGROUND: The Resuscitation Science Symposium (ReSS) is the dedicated
      international forum for resuscitation science at the American Heart Association's
      Scientific Sessions. In an attempt to increase curated content and social media
      presence during ReSS 2017, the Journal of the American Heart Association (JAHA)
      coordinated an inaugural social media campaign. METHODS AND RESULTS: Before ReSS,
      8 resuscitation science professionals were recruited from a convenience sample of
      attendees at ReSS 2017. Each blogger was assigned to either a morning or an
      afternoon session, responsible for "live tweeting" with the associated hashtags
      #ReSS17 and #AHA17. Twitter analytics from the 8 bloggers were collected from
      November 10 to 13, 2017. The primary outcome was Twitter impressions. Secondary
      outcomes included Twitter engagement and Twitter engagement rate. In total, 8
      bloggers (63% male) generated 591 tweets that garnered 261 050 impressions, 8013
      engagements, 928 retweets, 1653 likes, 292 hashtag clicks, and a median
      engagement rate of 2.4%. Total engagement, likes, and hashtag clicks were highest
      on day 2; total impressions were highest on day 3, and retweets were highest on
      day 4. Total impressions were highly correlated with the total number of tweets
      (r=0.87; P=0.005) and baseline number of Twitter followers for each blogger
      (r=0.78; P=0.02). CONCLUSION: In this inaugural social media campaign for the
      2017 American Heart Association ReSS, the degree of online engagement with this
      content by end users was quite good when evaluated by social media standards.
      Benchmarks for end-user interactions in the scientific community are undefined
      and will require further study.

PMID- 29654199
TI  - Estrogen Deficiency Promotes Cerebral Aneurysm Rupture by Upregulation of Th17
      Cells and Interleukin-17A Which Downregulates E-Cadherin.
AB  - BACKGROUND: Estrogen deficiency is associated with the development of cerebral
      aneurysms; however, the mechanism remains unknown. We explored the pathway of
      cerebral aneurysm development by investigating the potential link between
      estrogen deficiency and inflammatory factors. METHODS AND RESULTS: First, we
      established the role of interleukin-17 (IL-17)A. We performed a cytokine screen
      demonstrating that IL-17A is significantly expressed in mouse and human aneurysms
      (P=0.03). Likewise, IL-17A inhibition was shown to prevent aneurysm formation by
      42% (P=0.02) and rupture by 34% (P<0.05). Second, we found that estrogen
      deficiency upregulates T helper 17 cells and IL-17A and promotes aneurysm
      rupture. Estrogen-deficient mice had more ruptures than control mice (47% versus
      7%; P=0.04). Estradiol supplementation or IL-17A inhibition decreased the number
      of ruptures in estrogen-deficient mice (estradiol 6% versus 37%; P=0.04; IL-17A
      inhibition 18% versus 47%; P=0.018). Third, we found that IL-17A-blockade
      protects against aneurysm formation and rupture by increased E-cadherin
      expression. IL-17-inhibited mice had increased E-cadherin expression (P=0.003). E
      cadherin inhibition reversed the protective effect of IL-17A inhibition and
      increased the rate of aneurysm formation (65% versus 28%; P=0.04) and rupture
      (12% versus 0%; P=0.22). However, E-cadherin inhibition alone does not
      significantly increase aneurysm formation in normal mice or in estrogen-deficient
      mice. In cell migration assays, E-cadherin inhibition promoted macrophage
      infiltration across endothelial cells (P<0.05), which may be the mechanism for
      the estrogen deficiency/IL-17/E-cadherin aneurysm pathway. CONCLUSIONS: Our data
      suggest that estrogen deficiency promotes cerebral aneurysm rupture by
      upregulating IL-17A, which downregulates E-cadherin, encouraging macrophage
      infiltration in the aneurysm vessel wall.

PMID- 29654200
TI  - Transcatheter Aortic Valve Replacement in Low-Flow Aortic Stenosis: Treat the
      Flow or Treat the Patient?

PMID- 29654201
TI  - Frequency of Care and Mortality Following an Incident Diagnosis of Peripheral
      Artery Disease in the Inpatient or Outpatient Setting: The ARIC (Atherosclerosis
      Risk in Communities) Study.
AB  - BACKGROUND: Available health services data for individuals with peripheral artery
      disease (PAD) are often from studies of those eligible for or undergoing
      intervention. Knowledge of the frequency of care and mortality following an
      initial PAD diagnosis by setting (outpatient versus inpatient) is limited and
      represents an opportunity to provide new benchmark information. METHODS AND
      RESULTS: The purpose of this study was to characterize the frequency of care and
      mortality following an incident PAD diagnosis in the outpatient or inpatient
      setting using data from the ARIC (Atherosclerosis Risk in Communities) study
      cohort linked with Centers for Medicare and Medicaid Services fee-for-service
      claims data (2002-2012). Direct standardization was used to estimate age
      standardized rates of encounters and mortality. PAD was defined by billing code
      in any claim position. We observed 1086 incident PAD cases (873 outpatient, 213
      inpatient). At 1 year after diagnosis, participants diagnosed in the outpatient
      setting had 2.15 (95% confidence interval [CI], 2.10-2.21) PAD-related outpatient
      encounters per person-year, and 6.4% (95% CI, 4.8-8.1) had a PAD-related
      hospitalization. Conversely, participants diagnosed in the inpatient setting had
      1.02 (95% CI, 0.94-1.10) PAD-related outpatient encounters per person-year, and
      14.2% (95% CI, 9.3-18.7) had a PAD-related rehospitalization. One-year mortality
      was 7.1% (95% CI, 5.4-8.7) and 16.0% (95% CI, 11.0-21.1) among those diagnosed in
      outpatient and inpatient settings, respectively. CONCLUSIONS: This study provides
      important data estimating frequency of care and mortality by the setting of
      initial PAD diagnosis. Individuals with PAD are frequent users of health care,
      and those diagnosed in the inpatient setting have high rates of rehospitalization
      and mortality.

PMID- 29654202
TI  - Ideal Cardiovascular Health and Adiposity: Implications in Youth.
AB  - BACKGROUND: The American Heart Association set 2020 Strategic Impact Goals that
      defined cardiovascular risk factors to be included in the concept of ideal
      cardiovascular health (ICH). The prevalence of ICH among differing levels of
      adiposity in youth, especially severe obesity, is uncertain. METHODS AND RESULTS:
      The cross-sectional study measured ICH metrics in 300 children and adolescents
      stratified by adiposity: normal weight, overweight/obese, and severely obese. ICH
      incorporates 7 behavioral and health metrics, and was characterized as poor,
      intermediate, or ideal. Individual ICH metrics were transformed into standardized
      sample z-scores; a summary ICH sample z-score was also calculated. Multivariable
      linear regression models were used to estimate differences in ICH sample z-scores
      by adiposity status. Of the 300 participants, 113 were classified as having
      normal weight, 87 as having overweight/obesity, and 100 as having severe obesity
      (mean age 12.8 years, SD 2.7; 48% female). No participants met the criteria for
      ICH; 80% of those classified as having normal weight, 81% of those with
      overweight/obesity, and all of those with severe obesity were in poor
      cardiovascular health. After multivariable adjustment, those with
      overweight/obesity (sample z-score: -1.35; 95% confidence interval, -2.3, -1.1)
      and severe obesity (sample z-score: -1.45; 95% confidence interval, -2.9, -0.92)
      had lower overall ICH sample z-scores compared with participants with normal
      weight. Results were similar for individual ICH metrics. CONCLUSIONS: Poor
      cardiovascular health was highly prevalent in youth; ICH sample z-scores
      increased across levels of adiposity. Youth with obesity, particularly those with
      severe obesity, remain a rich target for primary prevention efforts. CLINICAL
      TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier:
      NCT01508598.

PMID- 29654203
TI  - Mineralocorticoid Receptor Antagonism in Patients With Atrial Fibrillation:
      Findings From the ORBIT-AF (Outcomes Registry for Better Informed Treatment of
      Atrial Fibrillation) Registry.
AB  - BACKGROUND: Mineralocorticoid receptor antagonist (MRA) therapy may be beneficial
      to patients with atrial fibrillation (AF), but little is known about their use in
      patients with AF and subsequent outcomes. METHODS AND RESULTS: In order to better
      understand MRA use and subsequent outcomes, we performed a retrospective cohort
      study of the contemporary ORBIT-AF (Outcomes Registry for Better Informed
      Treatment of Atrial Fibrillation) registry. AF progression and cardiovascular
      outcomes were compared using propensity-matched Cox proportional hazards modeling
      according to MRA use at baseline and new MRA use at follow-up versus patients
      with no MRA use. Among 7012 patients with nonpermanent AF, 320 patients were
      taking MRA at enrollment, and 416 patients initiated MRA use during follow-up.
      The mean patient age was 72.5 years, 56.3% were men, and 70.4% had paroxysmal AF.
      Among all patients taking MRAs, 434 (59.0%) had heart failure, 655 (89.0%) had
      hypertension, and 380 (51.6%) had both. After adjustment, new MRA use was not
      associated with reduced AF progression (hazard ratio, 1.18; 95% confidence
      interval, 0.88-1.58; P=0.27) but showed a trend towards lower risk of stroke,
      transient ischemic attack, or systemic embolism (hazard ratio, 0.17; 95%
      confidence interval, 0.02-1.23; P=0.08). Results were similar for a comparison of
      new MRA users and baseline MRA users compared with nonusers. CONCLUSIONS: In
      community-based outpatients with AF, the majority of MRA use was for heart
      failure and hypertension. MRA use also trended towards lower adjusted stroke
      risk. Future studies should test the hypothesis that MRA use may decrease the
      risk of stroke in patients with AF.

PMID- 29654204
TI  - Incidence, Predictors, and Clinical Impact of Early Prasugrel Cessation in
      Patients With ST-Elevation Myocardial Infarction.
AB  - BACKGROUND: Early withdrawal of recommended antiplatelet treatment with
      clopidogrel adversely affects prognosis following percutaneous coronary
      interventions. Optimal antiplatelet treatment is essential following ST-segment
      elevation myocardial infarction (STEMI) given the increased risk of thrombotic
      complications. This study assessed the frequency, predictors, and clinical impact
      of early prasugrel cessation in patients with STEMI undergoing primary
      percutaneous coronary interventions. METHODS AND RESULTS: We pooled patients with
      STEMI discharged on prasugrel in 2 prospective registries (Bern PCI Registry
      [NCT02241291] and SPUM-ACS (Inflammation and Acute Coronary Syndromes)
      [NCT01000701]) and 1 STEMI trial (COMFORTABLE-AMI (Comparison of Biomatrix Versus
      Gazelle in ST-Elevation Myocardial Infarction) [NCT00962416]). Prasugrel
      treatment status at 1 year was categorized as no cessation; crossover to another
      P2Y12-inhibitor; physician-recommended discontinuation; and disruption because of
      bleeding, side effects, or patient noncompliance. In time-dependent analyses, we
      assessed the impact of prasugrel cessation on the primary end point, a composite
      of cardiac death, myocardial infarction, and stroke. Of all 1830 included
      patients (17% women, mean age 59 years), 83% were treated with new-generation
      drug-eluting stents. At 1 year, any prasugrel cessation had occurred in 13.8% of
      patients including crossover (7.2%), discontinuation (3.7%), and disruption
      (2.9%). Independent predictors of any prasugrel cessation included female sex,
      age, and history of cerebrovascular event. The primary end point occurred in 5.2%
      of patients and was more frequent following disruption (hazard ratio 3.04, 95%
      confidence interval,1.34-6.91; P=0.008), without significant impact of crossover
      or discontinuation. Consistent findings were observed for all-cause death,
      myocardial infarction, and stent thrombosis following prasugrel disruption.
      CONCLUSIONS: In this contemporary study of patients with STEMI, early prasugrel
      cessation was not uncommon and primarily involved change to another P2Y12
      inhibitor. Disruption was the only type of early prasugrel cessation associated
      with statistically significant excess in ischemic risk within 1 year following
      primary percutaneous coronary interventions.

PMID- 29654205
TI  - Acute Kidney Injury in Diabetic Patients With Acute Myocardial Infarction: Role
      of Acute and Chronic Glycemia.
AB  - BACKGROUND: In acute myocardial infarction, acute hyperglycemia is a predictor of
      acute kidney injury (AKI), particularly in patients without diabetes mellitus.
      This emphasizes the importance of an acute glycemic rise rather than glycemia
      level at admission. We investigated whether, in diabetic patients with acute
      myocardial infarction, the combined evaluation of acute and chronic glycemic
      levels may have better prognostic value for AKI than admission glycemia. METHODS
      AND RESULTS: At admission, we prospectively measured glycemia and estimated
      average chronic glucose levels (mg/dL) using glycosylated hemoglobin (HbA1c),
      according to the following formula: 28.7*HbA1c (%)-46.7. We evaluated the
      association with AKI of the acute/chronic glycemic ratio and of the difference
      between acute and chronic glycemia (DeltaA-C). We enrolled 474 diabetic patients
      with acute myocardial infarction. Of them, 77 (16%) experienced AKI. The
      incidence of AKI increased in parallel with the acute/chronic glycemic ratio
      (12%, 14%, 22%; P=0.02 for trend) and DeltaA-C (13%, 13%, 23%; P=0.01) but not
      with admission glycemic tertiles (P=0.22). At receiver operating characteristic
      analysis, the acute/chronic glycemic ratio (area under the curve: 0.62 [95%
      confidence interval, 0.55-0.69]; P=0.001) and DeltaA-C (area under the curve:
      0.62 [95% confidence interval, 0.54-0.69]; P=0.002) accurately predicted AKI,
      without difference in the area under the curve between them (P=0.53). At
      reclassification analysis, the addition of the acute/chronic glycemic ratio and
      DeltaA-C to acute glycemia allowed proper AKI risk prediction in 16% of patients.
      CONCLUSIONS: In diabetic patients with acute myocardial infarction, AKI is better
      predicted by the combined evaluation of acute and chronic glycemic values than by
      assessment of admission glycemia alone.

PMID- 29654206
TI  - Staged Percutaneous Intervention for Concurrent Chronic Total Occlusions in
      Patients With ST-Segment-Elevation Myocardial Infarction: A Systematic Review and
      Meta-Analysis.
AB  - BACKGROUND: Studies have shown that chronic total occlusion (CTO) in a noninfarct
      related artery in patients with ST-segment-elevation myocardial infarction is
      linked to increased mortality. It remains unclear whether staged
      revascularization of a noninfarct-related artery CTO in patients with ST-segment
      elevation myocardial infarction translates to improved outcomes. We performed a
      meta-analysis to compare outcomes between patients presenting with ST-segment
      elevation myocardial infarction with concurrent CTO who underwent percutaneous
      coronary intervention of noninfarct-related artery CTO versus those who did not.
      METHOD AND RESULTS: We conducted an electronic database search of all published
      data. The primary end point was major adverse cardiovascular events. Secondary
      end points were all-cause mortality, cardiovascular mortality, myocardial
      infarction, repeat revascularization with either percutaneous coronary
      intervention or coronary artery bypass grafting, stroke, and heart failure
      readmission. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed.
      Random effects model was used and heterogeneity was considered if I2 >25. Six
      studies (n=1253 patients) were included in the analysis. There was a significant
      difference in major adverse cardiovascular events (OR, 0.54; 95% CI, 0.32-0.91),
      cardiovascular mortality (OR, 0.43; 95% CI, 0.20-0.95), and heart failure
      readmissions (OR, 0.57; 95% CI, 0.36-0.89), favoring the patients in the CTO
      percutaneous coronary intervention group. No significant differences were
      observed between the 2 groups for all-cause mortality (OR, 0.47; 95% CI, 0.22
      1.00), myocardial infarction (OR, 0.78; 95% CI, 0.41-1.46), repeat
      revascularization (OR, 1.13; 95% CI, 0.56-2.27), and stroke (OR, 0.51; 95% CI,
      0.20-1.33). CONCLUSIONS: In this meta-analysis, CTO percutaneous coronary
      intervention of the noninfarct-related artery in patients presenting with ST
      segment-elevation myocardial infarction was associated with a significant
      reduction in major adverse cardiovascular events, cardiovascular mortality, and
      heart failure readmissions.

PMID- 29654207
TI  - Evaluation of Acute Kidney Injury and Mortality After Intensive Blood Pressure
      Control in Patients With Intracerebral Hemorrhage.
AB  - BACKGROUND: We sought to assess the risk of acute kidney injury (AKI) and
      mortality associated with intensive systolic blood pressure reduction in acute
      intracerebral hemorrhage. METHODS AND RESULTS: Patients with acute intracerebral
      hemorrhage had spontaneous cause and symptom onset within 24 hours. We excluded
      patients with structural causes, coagulopathy, thrombocytopenia, and preexisting
      end-stage renal disease. We defined AKI using the Acute Kidney Injury Network
      criteria. Chronic kidney disease status was included in risk stratification and
      was defined by Kidney Disease Outcomes Quality Initiative staging. Maximum
      systolic blood pressure reduction was defined over a 12-hour period and
      dichotomized using receiver operating characteristic curve analysis. Descriptive
      statistics were done using independent sample t tests, chi2 tests, and Mann
      Whitney U tests, whereas multivariable logistic regression analysis was used to
      evaluate for predictors for AKI and mortality. A total of 448 patients with
      intracerebral hemorrhage met inclusion criteria. Maximum systolic blood pressure
      reduction was dichotomized to 90 mm Hg and found to increase the risk of AKI in
      patients with normal renal function (odds ratio, 2.1; 95% confidence interval,
      1.19-3.62; P=0.010) and chronic kidney disease (odds ratio, 3.91; 95% confidence
      interval, 1.26-12.15; P=0.019). The risk of AKI was not significantly different
      in normal renal function versus chronic kidney disease groups when adjusted for
      demographics, presentation characteristics, and medications associated with AKI.
      AKI positively predicted mortality for patients with normal renal function (odds
      ratio, 2.41; 95% confidence interval, 1.11-5.22; P=0.026) but not for patients
      with chronic kidney disease (odds ratio, 3.13; 95% confidence interval, 0.65
      15.01; P=0.154). CONCLUSIONS: These results indicate that intensive systolic
      blood pressure reduction with a threshold >90 mm Hg in patients with acute
      intracerebral hemorrhage may be an independent predictor for AKI.

PMID- 29654209
TI  - Crucial Role of Linear Ubiquitin Chain Assembly Complex-Mediated Inhibition of
      Programmed Cell Death in TLR4-Mediated B Cell Responses and B1b Cell Development.
AB  - Linear ubiquitin chain assembly complex (LUBAC)-mediated linear polyubiquitin
      plays crucial roles in thymus-dependent and -independent type II Ab responses and
      B1 cell development. In this study, we analyzed the role of LUBAC in TLR-mediated
      B cell responses. A mouse strain in which LUBAC activity was ablated specifically
      in B cells (B-HOIPDeltalinear mice) showed defective Ab responses to a type I
      thymus-independent Ag, NP-LPS. B cells from B-HOIPDeltalinear mice
      (HOIPDeltalinear B cells) underwent massive cell death in response to stimulation
      of TLR4, but not TLR9. TLR4 stimulation induced caspase-8 activation in
      HOIPDeltalinear B cells; this phenomenon, as well as TLR4-induced cell death, was
      suppressed by ablation of TRIF, a signal inducer specific for TLR4. In addition,
      LPS-induced survival, proliferation, and differentiation into Ab-producing cells
      of HOIPDeltalinear B cells were substantially restored by inhibition of caspases
      together with RIP3 deletion, but not by RIP3 deletion alone, suggesting that LPS
      stimulation kills HOIPDeltalinear B cells by apoptosis elicited via the TRIF
      pathway. Further examination of the roles of cell death pathways in B
      HOIPDeltalinear mice revealed that deletion of RIP3 increased the number of B1
      cells, particularly B1b cells, in B-HOIPDeltalinear mice, indicating that B1b
      cell homeostasis is controlled via LUBAC-mediated suppression of necroptosis.
      Taken together, the data show that LUBAC regulates TLR4-mediated B cell responses
      and B1b cell development and/or maintenance by inhibiting programmed cell death.

PMID- 29654208
TI  - A Nonpyroptotic IFN-gamma-Triggered Cell Death Mechanism in Nonphagocytic Cells
      Promotes Salmonella Clearance In Vivo.
AB  - The cytokine IFN-gamma has well-established antibacterial properties against the
      bacterium Salmonella enterica in phagocytes, but less is known about the effects
      of IFN-gamma on Salmonella-infected nonphagocytic cells, such as intestinal
      epithelial cells (IECs) and fibroblasts. In this article, we show that exposing
      human and murine IECs and fibroblasts to IFN-gamma following infection with
      Salmonella triggers a novel form of cell death that is neither pyroptosis nor any
      of the major known forms of programmed cell death. Cell death required IFN-gamma
      signaling via STAT1-IRF1-mediated induction of guanylate binding proteins and the
      presence of live Salmonella in the cytosol. In vivo, ablating IFN-gamma signaling
      selectively in murine IECs led to higher bacterial burden in colon contents and
      increased inflammation in the intestine of infected mice. Together, these results
      demonstrate that IFN-gamma signaling triggers release of Salmonella from the
      Salmonella-containing vacuole into the cytosol of infected nonphagocytic cells,
      resulting in a form of nonpyroptotic cell death that prevents bacterial spread in
      the gut.

PMID- 29654210
TI  - c-Myb Coordinates Survival and the Expression of Genes That Are Critical for the
      Pre-BCR Checkpoint.
AB  - The c-Myb transcription factor is required for adult hematopoiesis, yet little is
      known about c-Myb function during lineage-specific differentiation due to the
      embryonic lethality of Myb-null mutations. We previously used tissue-specific
      inactivation of the murine Myb locus to demonstrate that c-Myb is required for
      differentiation to the pro-B cell stage, survival during the pro-B cell stage,
      and the pro-B to pre-B cell transition during B lymphopoiesis. However, few
      downstream mediators of c-Myb-regulated function have been identified. We
      demonstrate that c-Myb regulates the intrinsic survival of CD19+ pro-B cells in
      the absence of IL-7 by repressing expression of the proapoptotic proteins Bmf and
      Bim and that levels of Bmf and Bim mRNA are further repressed by IL-7 signaling
      in pro-B cells. c-Myb regulates two crucial components of the IL-7 signaling
      pathway: the IL-7Ralpha-chain and the negative regulator SOCS3 in CD19+ pro-B
      cells. Bypassing IL-7R signaling through constitutive activation of Stat5b
      largely rescues survival of c-Myb-deficient pro-B cells, whereas constitutively
      active Akt is much less effective. However, rescue of pro-B cell survival is not
      sufficient to rescue proliferation of pro-B cells or the pro-B to small pre-B
      cell transition, and we further demonstrate that c-Myb-deficient large pre-B
      cells are hypoproliferative. Analysis of genes crucial for the pre-BCR checkpoint
      demonstrates that, in addition to IL-7Ralpha, the genes encoding lambda5, cyclin
      D3, and CXCR4 are downregulated in the absence of c-Myb, and lambda5 is a direct
      c-Myb target. Thus, c-Myb coordinates survival with the expression of genes that
      are required during the pre-BCR checkpoint.

PMID- 29654211
TI  - Efficacy and Mechanism of Antitumor Activity of an Antibody Targeting Transferrin
      Receptor 1 in Mouse Models of Human Multiple Myeloma.
AB  - The transferrin receptor 1 (TfR1) is an attractive target for Ab-mediated cancer
      therapy. We previously developed a mouse/human chimeric IgG3 Ab (ch128.1)
      targeting human TfR1, which exhibits direct in vitro cytotoxicity against certain
      human malignant B cells through TfR1 degradation and iron deprivation. ch128.1
      also demonstrates exceptional antitumor activity against the B cell malignancy
      multiple myeloma (MM) in xenograft models of SCID-Beige mice bearing either
      disseminated ARH-77 or KMS-11 cells in an early disease setting. Interestingly,
      this activity is observed even against KMS-11 cells, which show no sensitivity to
      the direct cytotoxic activity of ch128.1 in vitro. To understand the
      contributions of the Fc fragment, we generated a ch128.1 mutant with impaired
      binding to FcgammaRs and to the complement component C1q, which retains binding
      to the neonatal Fc receptor. We now report that this mutant Ab does not show
      antitumor activity in these two MM models, indicating a crucial role of the Fc
      fragment in the antitumor activity of ch128.1, which can be attributed to
      effector functions (Ab-dependent cell-mediated cytotoxicity, Ab-dependent cell
      mediated phagocytosis, and/or complement-dependent cytotoxicity). Interestingly,
      in the KMS-11 model, complement depletion does not affect protection, whereas
      macrophage depletion does. Consistent with this observation, we found that
      ch128.1 induces Ab-dependent cell-mediated cytotoxicity and Ab-dependent cell
      mediated phagocytosis against KMS-11 cells in the presence of murine bone marrow
      derived macrophages. Finally, we found that ch128.1 therapy effectively increases
      survival in a late MM disease setting. Our results suggest that macrophages play
      a major role in ch128.1-mediated antitumor protection in our models and that
      ch128.1 can be effective against human B cell malignancies such as MM.

PMID- 29654212
TI  - Modifying Enzymes Are Elicited by ER Stress, Generating Epitopes That Are
      Selectively Recognized by CD4+ T Cells in Patients With Type 1 Diabetes.
AB  - In spite of tolerance mechanisms, some individuals develop T-cell-mediated
      autoimmunity. Posttranslational modifications that increase the affinity of
      epitope presentation and/or recognition represent one means through which self
      tolerance mechanisms can be circumvented. We investigated T-cell recognition of
      peptides that correspond to modified beta-cell antigens in subjects with type 1
      diabetes. Modified peptides elicited enhanced proliferation by autoreactive T
      cell clones. Endoplasmic reticulum (ER) stress in insulinoma cells increased
      cytosolic calcium and the activity of tissue transglutaminase 2 (tTG2).
      Furthermore, stressed human islets and insulinomas elicited effector responses
      from T cells specific for modified peptides, suggesting that ER stress-derived
      tTG2 activity generated deamidated neoepitopes that autoreactive T cells
      recognized. Patients with type 1 diabetes had large numbers of T cells specific
      for these epitopes in their peripheral blood. T cells with these specificities
      were also isolated from the pancreatic draining lymph nodes of cadaveric donors
      with established diabetes. Together, these results suggest that self-antigens are
      enzymatically modified in beta-cells during ER stress, giving rise to modified
      epitopes that could serve to initiate autoimmunity or to further broaden the
      antigenic repertoire, activating potentially pathogenic CD4+ T cells that may not
      be effectively eliminated by negative selection.

PMID- 29654213
TI  - Zinc Inhibits Phosphate-Induced Vascular Calcification through TNFAIP3-Mediated
      Suppression of NF-kappaB.
AB  - Background The high cardiovascular morbidity and mortality of patients with CKD
      may result in large part from medial vascular calcification, a process promoted
      by hyperphosphatemia and involving osteo-/chondrogenic transdifferentiation of
      vascular smooth muscle cells (VSMCs). Reduced serum zinc levels have frequently
      been observed in patients with CKD, but the functional relevance of this remains
      unclear.Methods We performed experiments in primary human aortic VSMCs; klotho
      hypomorphic (kl/kl), subtotal nephrectomy, and cholecalciferol-overload mouse
      calcification models; and serum samples from patients with CKD.Results In
      cultured VSMCs, treatment with zinc sulfate (ZnSO4) blunted phosphate-induced
      calcification, osteo-/chondrogenic signaling, and NF-kappaB activation. ZnSO4
      increased the abundance of zinc-finger protein TNF-alpha-induced protein 3
      (TNFAIP3, also known as A20), a suppressor of the NF-kappaB pathway, by zinc
      sensing receptor ZnR/GPR39-dependent upregulation of TNFAIP3 gene expression.
      Silencing of TNFAIP3 in VSMCs blunted the anticalcific effects of ZnSO4 under
      high phosphate conditions. kl/kl mice showed reduced plasma zinc levels, and
      ZnSO4 supplementation strongly blunted vascular calcification and aortic
      osteoinduction and upregulated aortic Tnfaip3 expression. ZnSO4 ameliorated
      vascular calcification in mice with chronic renal failure and mice with
      cholecalciferol overload. In patients with CKD, serum zinc concentrations
      inversely correlated with serum calcification propensity. Finally, ZnSO4
      ameliorated the osteoinductive effects of uremic serum in VSMCs.Conclusions Zinc
      supplementation ameliorates phosphate-induced osteo-/chondrogenic
      transdifferentiation of VSMCs and vascular calcification through an active
      cellular mechanism resulting from GPR39-dependent induction of TNFAIP3 and
      subsequent suppression of the NF-kappaB pathway. Zinc supplementation may be a
      simple treatment to reduce the burden of vascular calcification in CKD.

PMID- 29654214
TI  - Four-Dimensional Imaging of T Cells in Kidney Transplant Rejection.
AB  - Kidney transplantation is the treatment of choice for ESRD but is complicated by
      the response of the recipient's immune system to nonself histocompatibility
      antigens on the graft, resulting in rejection. Multiphoton intravital microscopy,
      referred to as four-dimensional imaging because it records dynamic events in
      three-dimensional tissue volumes, has emerged as a powerful tool to study
      immunologic processes in living animals. Here, we will review advances in
      understanding the complex mechanisms of T cell-mediated rejection made possible
      by four-dimensional imaging of mouse renal allografts. We will summarize recent
      data showing that activated (effector) T cell migration to the graft is driven by
      cognate antigen presented by dendritic cells that surround and penetrate
      peritubular capillaries, and that T cell-dendritic cell interactions persist in
      the graft over time, maintaining the immune response in the tissue.

PMID- 29654215
TI  - NPHP1 (Nephrocystin-1) Gene Deletions Cause Adult-Onset ESRD.
AB  - Background Nephronophthisis (NPH) is the most prevalent genetic cause for ESRD in
      children. However, little is known about the prevalence of NPH in adult-onset
      ESRD. Homozygous full gene deletions of the NPHP1 gene encoding nephrocystin-1
      are a prominent cause of NPH. We determined the prevalence of NPH in adults by
      assessing homozygous NPHP1 full gene deletions in adult-onset ESRD.Methods Adult
      renal transplant recipients from five cohorts of the International Genetics and
      Translational Research in Transplantation Network (iGeneTRAiN) underwent single
      nucleotide polymorphism genotyping. After quality control, we determined
      autosomal copy number variants (such as deletions) on the basis of median log2
      ratios and B-allele frequency patterns. The findings were independently validated
      in one cohort. Patients were included in the analysis if they had adult-onset
      ESRD, defined as start of RRT at >=18 years old.Results We included 5606 patients
      with adult-onset ESRD; 26 (0.5%) showed homozygous NPHP1 deletions. No donor
      controls showed homozygosity for this deletion. Median age at ESRD onset was 30
      (range, 18-61) years old for patients with NPH, with 54% of patients age >=30
      years old. Notably, only three (12%) patients were phenotypically classified as
      having NPH, whereas most patients were defined as having CKD with unknown
      etiology (n=11; 42%).Conclusions Considering that other mutation types in NPHP1
      or mutations in other NPH-causing genes were not analyzed, NPH is a relatively
      frequent monogenic cause of adult-onset ESRD. Because 88% of patients had not
      been clinically diagnosed with NPH, wider application of genetic testing in adult
      onset ESRD may be warranted.

PMID- 29654218
TI  - p53: emerging roles in stem cells, development and beyond.
AB  - Most human cancers harbor mutations in the gene encoding p53. As a result,
      research on p53 in the past few decades has focused primarily on its role as a
      tumor suppressor. One consequence of this focus is that the functions of p53 in
      development have largely been ignored. However, recent advances, such as the
      genomic profiling of embryonic stem cells, have uncovered the significance and
      mechanisms of p53 functions in mammalian cell differentiation and development. As
      we review here, these recent findings reveal roles that complement the well
      established roles for p53 in tumor suppression.

PMID- 29654219
TI  - An interview with Christiana Ruhrberg.
AB  - Christiana Ruhrberg is Professor of Neuronal and Vascular Biology at the UCL
      Institute of Ophthalmology in London. Her lab investigates the relationship
      between nerve and blood vessel development in the central nervous system. In
      2018, she was awarded the British Society for Developmental Biology's Cheryll
      Tickle Medal, which recognises outstanding achievements of mid-career female
      scientists in the field. In advance of her medal lecture at the society's spring
      meeting, we met Christiana to find out what the award means to her, how she
      settled on neurovascular development after many changes in direction early in her
      career and her thoughts on what makes a good scientific mentor.

PMID- 29654220
TI  - Cysteine Scanning Mutagenesis of TM4b-4c Loop of Glutamate Transporter EAAT1
      Reveals Three Conformationally Sensitive Residues.
AB  - Glutamatergic synaptic transmitters are cleared from the synaptic cleft through
      excitatory amino acid transporters (EAATs) that are responsible for recycling
      glutamate and transporting it into neurons and glial cells. To probe the
      structural role of the TM4b-4c loop of EAAT1 (Rattus norvegicus), each of the 57
      amino acid residues was mutated to cysteine. Thirteen of the single mutants have
      very low transport activity. Aqueous accessibility of the introduced cysteines
      from the remaining mutants was then explored by membrane-permeant and membrane
      impermeant sulfhydryl reagents in different conditions. F190C, V238C, and A243C
      were affected by MTSET, whereas Q189C, F190C, V238C, A243C, and L244C were
      sensitive to MTSEA. Q189C and L244C transport activity was diminished in the
      presence of potassium, which is expected to favor the inward-facing conformation
      of the transporter. Inversely, L244C was protected by glutamate. The modification
      of A243C by MTSEA was enhanced by either potassium and glutamate or dl-threo-beta
      benzyloxyaspartate. From these results, we suggest that residues F190C, V238C,
      and A243C may be located near the extracellular surface, and the TM4b-4c loop
      forms multiple reentrant membrane loops on the cell surface. Alternatively,
      F190C, V238C, and A243C may function in the transport pathway, which is exposed
      to MTSET. In addition, Q189C, A243C, and L244C are conformationally sensitive and
      may play a role in the transport cycle.

PMID- 29654216
TI  - Glycine Amidinotransferase (GATM), Renal Fanconi Syndrome, and Kidney Failure.
AB  - Background For many patients with kidney failure, the cause and underlying defect
      remain unknown. Here, we describe a novel mechanism of a genetic order
      characterized by renal Fanconi syndrome and kidney failure.Methods We clinically
      and genetically characterized members of five families with autosomal dominant
      renal Fanconi syndrome and kidney failure. We performed genome-wide linkage
      analysis, sequencing, and expression studies in kidney biopsy specimens and renal
      cells along with knockout mouse studies and evaluations of mitochondrial
      morphology and function. Structural studies examined the effects of recognized
      mutations.Results The renal disease in these patients resulted from monoallelic
      mutations in the gene encoding glycine amidinotransferase (GATM), a renal
      proximal tubular enzyme in the creatine biosynthetic pathway that is otherwise
      associated with a recessive disorder of creatine deficiency. In silico analysis
      showed that the particular GATM mutations, identified in 28 members of the five
      families, create an additional interaction interface within the GATM protein and
      likely cause the linear aggregation of GATM observed in patient biopsy specimens
      and cultured proximal tubule cells. GATM aggregates-containing mitochondria were
      elongated and associated with increased ROS production, activation of the NLRP3
      inflammasome, enhanced expression of the profibrotic cytokine IL-18, and
      increased cell death.Conclusions In this novel genetic disorder, fully penetrant
      heterozygous missense mutations in GATM trigger intramitochondrial fibrillary
      deposition of GATM and lead to elongated and abnormal mitochondria. We speculate
      that this renal proximal tubular mitochondrial pathology initiates a response
      from the inflammasome, with subsequent development of kidney fibrosis.

PMID- 29654221
TI  - Correction for Anthony et al., "Cooperation between Strain-Specific and Broadly
      Neutralizing Responses Limited Viral Escape and Prolonged the Exposure of the
      Broadly Neutralizing Epitope".

PMID- 29654217
TI  - The role of mitochondria in stem cell fate and aging.
AB  - The importance of mitochondria in energy metabolism, signal transduction and
      aging in post-mitotic tissues has been well established. Recently, the crucial
      role of mitochondrial-linked signaling in stem cell function has come to light
      and the importance of mitochondria in mediating stem cell activity is becoming
      increasingly recognized. Despite the fact that many stem cells exhibit low
      mitochondrial content and a reliance on mitochondrial-independent glycolytic
      metabolism for energy, accumulating evidence has implicated the importance of
      mitochondrial function in stem cell activation, fate decisions and defense
      against senescence. In this Review, we discuss the recent advances that link
      mitochondrial metabolism, homeostasis, stress responses, and dynamics to stem
      cell function, particularly in the context of disease and aging. This Review will
      also highlight some recent progress in mitochondrial therapeutics that may
      present attractive strategies for improving stem cell function as a basis for
      regenerative medicine and healthy aging.

PMID- 29654222
TI  - Correction for Chaumorcel et al., "The Human Cytomegalovirus Protein TRS1
      Inhibits Autophagy via Its Interaction with Beclin 1".

PMID- 29654223
TI  - Why be an optimist if you treat stroke?

PMID- 29654224
TI  - Correction: Vascular geometry of the extracranial carotid arteries: an analysis
      of length, diameter, and tortuosity.

PMID- 29654225
TI  - Correction: Optimizing endovascular stroke treatment: removing the microcatheter
      before clot retrieval with stent-retrievers increases aspiration flow.

PMID- 29654226
TI  - Metformin Enhances the Effect of Regorafenib and Inhibits Recurrence and
      Metastasis of Hepatic Carcinoma After Liver Resection via Regulating Expression
      of Hypoxia Inducible Factors 2alpha (HIF-2alpha) and 30 kDa HIV Tat-Interacting
      Protein (TIP30).
AB  - BACKGROUND Regorafenib (RGF) is the drug of choice for treating hepatic carcinoma
      (HCC), but the drug has drawbacks due to resistance and associated adverse
      effects. Thus, it becomes crucial to understand the causal 'map' of the
      resistance conferred by RGF, so that its clinical potency can be amplified,
      resulting in enhanced efficacy with reduced adverse effects. Metformin (MTF) has
      been reported to target NLK (Nemo-like kinase) to inhibit non-small lung cancer
      cells. Based on the literature, the present investigation was carried out to
      reveal the effect of RGF and MTF, with an expectation that MTF can synergize
      therapeutic potential as well reduce chances of resistance. MATERIAL AND METHODS
      Protein expression of hypoxia inducible factors (HIF)-2alpha, 30 kDa HIV Tat
      interacting protein (TIP30), E-cadherin, N-cadherin, and pAMPK were assessed by
      Western blot analysis. RGF and MTF were exposed to MHCC97H cell and proliferation
      was quantified by assay of cell viability. Gene silencing and chromatin
      immunoprecipitation assay were done to reveal the relationship between TIP30 and
      HIF-2alpha. The impact of RGF and MTF together on postoperative recurrence and
      lung metastasis of hepatocellular carcinoma was investigated using tumor
      engrafted mice after administration of MTF and RGF once daily for 35 days.
      Immunohistochemistry was used to reveal CD31, Ki67, and TUNEL. RESULTS The
      results suggested MTF-RGF combination lowered expression of HIF-2alpha gene
      silencing and suggested increased TIP30 after reduction of HIF-2alpha. The
      chromatin immunoprecipitation study indicated that under hypoxia, HIF-2alpha
      could bind with TIP30 promoter. Cell number quantification (CCK8), viable cell
      count, and apoptosis data (using Annexin V-FITC) indicated co-administration of
      RGF and MTF reduced cell proliferation, encouraging cell apoptosis, and reduced
      epithelial-mesenchymal transition course. Thus, in orthotopic mice, the RGF-MTF
      combination exhibited substantial reduction of HCC in lung metastasis and
      postoperative relapse. CONCLUSIONS MTF can enhance the potential of RGF and
      inhibit the recurrence and metastasis of HCC after postoperative liver section by
      regulating the levels of TIP30 and HIF-2alpha.

PMID- 29654227
TI  - An Unusual Manifestation of Calcineurin Inhibitor-Induced Pain Syndrome in Kidney
      Transplantation: A Case Report and Literature Review.
AB  - BACKGROUND Calcineurin inhibitors (CNI) are the mainstay immunosuppressive drugs
      for kidney transplantation. Although they provide excellent allograft and patient
      outcomes, adverse effects are frequently encountered. Calcineurin inhibitor
      induced pain syndrome (CIPS) is a rare adverse effect of CNI. Previous case
      reports with CIPS diagnosis involved incapacitating pain in the lower
      extremities. CASE REPORT In this article, we report the first case of CIPS with
      severe back pain as the presenting symptom, which was correlated with a high
      tacrolimus trough concentration due to a drug interaction with clotrimazole
      troche. Magnetic resonance imaging (MRI) of the spine showed bone marrow edema,
      which is consistent with previous case reports. The patient's symptoms resolved
      within 3 weeks of the onset of pain. Treatments were symptomatic care and
      lowering the tacrolimus trough concentration. Pain was improved significantly
      with pregabalin but not with nifedipine. CONCLUSIONS We reviewed the literature
      of kidney transplant cohorts with CIPS to ascertain prevalence, pain
      characteristics, and treatment outcomes. Apart from our case, all patients
      experienced lower extremities pain and were pain-free during the follow-up
      period, without any residual abnormalities. CIPS is a benign but adverse effect
      of CNI. Counselling patients about the disease's natural history and supportive
      care remain the best treatment.

PMID- 29654228
TI  - Interactions and scattering of quantum vortices in a polariton fluid.
AB  - Quantum vortices, the quantized version of classical vortices, play a prominent
      role in superfluid and superconductor phase transitions. However, their
      exploration at a particle level in open quantum systems has gained considerable
      attention only recently. Here we study vortex pair interactions in a resonant
      polariton fluid created in a solid-state microcavity. By tracking the vortices on
      picosecond time scales, we reveal the role of nonlinearity, as well as of density
      and phase gradients, in driving their rotational dynamics. Such effects are also
      responsible for the split of composite spin-vortex molecules into elementary half
      vortices, when seeding opposite vorticity between the two spinorial components.
      Remarkably, we also observe that vortices placed in close proximity experience a
      pull-push scenario leading to unusual scattering-like events that can be
      described by a tunable effective potential. Understanding vortex interactions can
      be useful in quantum hydrodynamics and in the development of vortex-based
      lattices, gyroscopes, and logic devices.

PMID- 29654230
TI  - Synthesis of a molecularly defined single-active site heterogeneous catalyst for
      selective oxidation of N-heterocycles.
AB  - Generally, a homogeneous catalyst exhibits good activity and defined active sites
      but it is difficult to recycle. Meanwhile, a heterogeneous catalyst can easily be
      reused but its active site is difficult to reveal. It is interesting to bridge
      the gap between homogeneous and heterogeneous catalysis via controllable
      construction of a heterogeneous catalyst containing defined active sites. Here,
      we report that a molecularly defined, single-active site heterogeneous catalyst
      has been designed and prepared via the oxidative polymerization of maleimide
      derivatives. These polymaleimide derivatives can be active catalysts for the
      selective oxidation of heterocyclic compounds to quinoline and indole via the
      recycling of -C=O and -C-OH groups, which was confirmed by tracing the reaction
      with GC-MS using maleimide as the catalyst and by FT-IR analysis with
      polymaleimide as the catalyst. These results might promote the development of
      heterogeneous catalysts with molecularly defined single active sites exhibiting a
      comparable activity to homogeneous catalysts.

PMID- 29654229
TI  - Somatic genome editing with the RCAS-TVA-CRISPR-Cas9 system for precision tumor
      modeling.
AB  - To accurately recapitulate the heterogeneity of human diseases, animal models
      require to recreate multiple complex genetic alterations. Here, we combine the
      RCAS-TVA system with the CRISPR-Cas9 genome editing tools for precise modeling of
      human tumors. We show that somatic deletion in neural stem cells of a variety of
      known tumor suppressor genes (Trp53, Cdkn2a, and Pten) leads to high-grade glioma
      formation. Moreover, by simultaneous delivery of pairs of guide RNAs we generate
      different gene fusions with oncogenic potential, either by chromosomal deletion
      (Bcan-Ntrk1) or by chromosomal translocation (Myb-Qk). Lastly, using homology
      directed-repair, we also produce tumors carrying the homologous mutation to human
      BRAF V600E, frequently identified in a variety of tumors, including different
      types of gliomas. In summary, we have developed an extremely versatile mouse
      model for in vivo somatic genome editing, that will elicit the generation of more
      accurate cancer models particularly appropriate for pre-clinical testing.

PMID- 29654231
TI  - Nonzero Berry phase in quantum oscillations from giant Rashba-type spin splitting
      in LaTiO3/SrTiO3 heterostructures.
AB  - The manipulation of the spin degrees of freedom in a solid has been of
      fundamental and technological interest recently for developing high-speed, low
      power computational devices. There has been much work focused on developing
      highly spin-polarized materials and understanding their behavior when
      incorporated into so-called spintronic devices. These devices usually require
      spin splitting with magnetic fields. However, there is another promising strategy
      to achieve spin splitting using spatial symmetry breaking without the use of a
      magnetic field, known as Rashba-type splitting. Here we report evidence for a
      giant Rashba-type splitting at the interface of LaTiO3 and SrTiO3. Analysis of
      the magnetotransport reveals anisotropic magnetoresistance, weak anti
      localization and quantum oscillation behavior consistent with a large Rashba-type
      splitting. It is surprising to find a large Rashba-type splitting in 3d
      transition metal oxide-based systems such as the LaTiO3/SrTiO3 interface, but it
      is promising for the development of a new kind of oxide-based spintronics.

PMID- 29654232
TI  - Directed evolution of broadly crossreactive chemokine-blocking antibodies
      efficacious in arthritis.
AB  - Chemokine receptors typically have multiple ligands. Consequently, treatment with
      a blocking antibody against a single chemokine is expected to be insufficient for
      efficacy. Here we show single-chain antibodies can be engineered for broad
      crossreactivity toward multiple human and mouse proinflammatory ELR+ CXC
      chemokines. The engineered molecules recognize functional epitopes of ELR+ CXC
      chemokines and inhibit neutrophil activation ex vivo. Furthermore, an albumin
      fusion of the most crossreactive single-chain antibody prevents and reverses
      inflammation in the K/BxN mouse model of arthritis. Thus, we report an approach
      for the molecular evolution and selection of broadly crossreactive antibodies
      towards a family of structurally related, yet sequence-diverse protein targets,
      with general implications for the development of novel therapeutics.

PMID- 29654233
TI  - Simultaneous complementary photoswitching of hemithioindigo tweezers for dynamic
      guest relocalization.
AB  - Remote control of complex molecular behavior and function is one key problem in
      modern chemistry. Using light signaling for this purpose has many advantages,
      however the integration of different photo processes into a wholesome yet complex
      system is highly challenging. Here we report an alternative approach to increase
      complexity of light control-simultaneous complementary photoswitching-in which
      spectral overlap is used as an advantage to drastically reduce the signaling
      needed for controlling multipart supramolecular assemblies. Two photoswitchable
      molecular tweezers respond to the same light signals with opposite changes in
      their binding affinities. In this way the configuration of two host tweezers and
      ultimately the dynamic relocation of a guest molecule can be trigged by only one
      signal reversibly in the same solution. This approach should provide a powerful
      tool for the construction of sophisticated, integrated, and multi-responsive
      smart molecular systems in any application driven field of chemistry.

PMID- 29654235
TI  - Metabolomics and pathway analyses to characterize metabolic alterations in
      pregnant dairy cows on D 17 and D 45 after AI.
AB  - Nutrient flow to the embryo and placenta is crucial for proper development and
      growth during pregnancy. In this study, a metabonomic analysis was undertaken to
      better understand global changes in pregnant dairy cows on D 17 and D 45 after
      timed artificial insemination (AI). Metabolic changes in the blood plasma of
      pregnant dairy cows were investigated using HPLC-MS and a multivariate
      statistical analysis. Changes in metabolic networks were established using the
      MetPA method. Alterations in six metabolic pathways were found on D 17 and D 45,
      including variations in the level of alpha-linolenic acid metabolism,
      glycerophospholipid metabolism, pentose and glucuronate interconversions,
      glycerolipid metabolism, folate biosynthesis, and tyrosine metabolism. In
      addition to these pathways, 9 metabolic pathways were markedly altered on D 45.
      These pathways included changes in the one-carbon pool caused by folate;
      phenylalanine, tyrosine and tryptophan biosynthesis; thiamine metabolism;
      pantothenate and CoA biosynthesis; purine metabolism; inositol phosphate
      metabolism; amino sugar and nucleotide sugar metabolism; pentose phosphate; and
      the TCA pathway. The combination of metabonomics and network methods used in this
      study generated rich biochemical insight into possible biological modules related
      to early pregnancy in dairy cows.

PMID- 29654234
TI  - Anchoring zero valence single atoms of nickel and iron on graphdiyne for hydrogen
      evolution.
AB  - Electrocatalysis by atomic catalysts is a major focus of chemical and energy
      conversion effort. Although transition-metal-based bulk electrocatalysts for
      electrochemical application on energy conversion processes have been reported
      frequently, anchoring the stable transition-metal atoms (e.g. nickel and iron)
      still remains a practical challenge. Here we report a strategy for fabrication of
      ACs comprising only isolated nickel/iron atoms anchored on graphdiyne. Our
      findings identify the very narrow size distributions of both nickel (1.23 A) and
      iron (1.02 A), typical sizes of single-atom nickel and iron. The precision of
      this method motivates us to develop a general approach in the field of single
      atom transition-metal catalysis. Such atomic catalysts have high catalytic
      activity and stability for hydrogen evolution reactions.

PMID- 29654236
TI  - Spinal cord gray matter segmentation using deep dilated convolutions.
AB  - Gray matter (GM) tissue changes have been associated with a wide range of
      neurological disorders and were recently found relevant as a biomarker for
      disability in amyotrophic lateral sclerosis. The ability to automatically segment
      the GM is, therefore, an important task for modern studies of the spinal cord. In
      this work, we devise a modern, simple and end-to-end fully-automated human spinal
      cord gray matter segmentation method using Deep Learning, that works both on in
      vivo and ex vivo MRI acquisitions. We evaluate our method against six
      independently developed methods on a GM segmentation challenge. We report state
      of-the-art results in 8 out of 10 evaluation metrics as well as major network
      parameter reduction when compared to the traditional medical imaging
      architectures such as U-Nets.

PMID- 29654237
TI  - Proteomic analysis at the sites of clinical infection with invasive Streptococcus
      pyogenes.
AB  - Invasive Streptococcus pyogenes infections are rare, with often-unexplained
      severity. Prompt diagnosis is desirable, as deaths can occur rapidly following
      onset and there is an increased, but preventable, risk to contacts. Here,
      proteomic analyses of clinical samples from invasive human S. pyogenes infections
      were undertaken to determine if novel diagnostic targets could be detected, and
      to augment our understanding of disease pathogenesis. Fluid samples from 17
      patients with confirmed invasive S. pyogenes infection (empyema, septic
      arthritis, necrotising fasciitis) were analysed by proteomics for streptococcal
      and human proteins; 16/17 samples had detectable S. pyogenes DNA. Nineteen unique
      S. pyogenes proteins were identified in just 6/17 samples, and 15 of these were
      found in a single pleural fluid sample including streptococcal inhibitor of
      complement, trigger factor, and phosphoglycerate kinase. In contrast, 469 human
      proteins were detected in patient fluids, 177 (38%) of which could be identified
      as neutrophil proteins, including alpha enolase and lactotransferrin which,
      together, were found in all 17 samples. Our data suggest that streptococcal
      proteins are difficult to detect in infected fluid samples. A vast array of human
      proteins associated with leukocyte activity are, however, present in samples that
      deserve further evaluation as potential biomarkers of infection.

PMID- 29654238
TI  - Transverse dielectrophoretic-based DNA nanoscale confinement.
AB  - Confinement of single molecules within nanoscale environments is crucial in a
      range of fields, including biomedicine, genomics, and biophysics. Here, we
      present a method that can concentrate, confine, and linearly stretch DNA
      molecules within a single optical field of view using dielectrophoretic (DEP)
      force. The method can convert an open surface into one confining DNA molecules
      without a requirement for bonding, hydrodynamic or mechanical components. We use
      a transverse DEP field between a top coverslip and a bottom substrate, both of
      which are coated with a transparent conductive material. Both layers are attached
      using double-sided tape, defining the chamber. The nanofeatures lie at the
      "floor" and do not require any bonding. With the application of an alternating
      (AC) electric field (2 Vp-p) between the top and bottom electrodes, a DEP field
      gradient is established and used to concentrate, confine and linearly extend DNA
      in nanogrooves as small as 100-nm in width. We also demonstrate reversible
      loading/unloading of DNA molecules into nanogrooves and nanopits by switching
      frequency (between 10 kHz to 100 kHz). The technology presented in this paper
      provides a new method for single-molecule trapping and analysis.

PMID- 29654239
TI  - Carboxythiazole is a key microbial nutrient currency and critical component of
      thiamin biosynthesis.
AB  - Almost all cells require thiamin, vitamin B1 (B1), which is synthesized via the
      coupling of thiazole and pyrimidine precursors. Here we demonstrate that 5-(2
      hydroxyethyl)-4-methyl-1,3-thiazole-2-carboxylic acid (cHET) is a useful in vivo
      B1 precursor for representatives of ubiquitous marine picoeukaryotic
      phytoplankton and Escherichia coli - drawing attention to cHET as a valuable
      exogenous micronutrient for microorganisms with ecological, industrial, and
      biomedical value. Comparative utilization experiments with the terrestrial plant
      Arabidopsis thaliana revealed that it can also use exogenous cHET, but notably,
      picoeukaryotic marine phytoplankton and E. coli were adapted to grow on low
      (picomolar) concentrations of exogenous cHET. Our results call for the
      modification of the conventional B1 biosynthesis model to incorporate cHET as a
      key precursor for B1 biosynthesis in two domains of life, and for consideration
      of cHET as a microbial micronutrient currency modulating marine primary
      productivity and community interactions in human gut-hosted microbiomes.

PMID- 29654240
TI  - Electrically Enhanced Self-Thermophoresis of Laser-Heated Janus Particles under a
      Rotating Electric Field.
AB  - The motion of a laser-heated Janus particle is experimentally measured under a
      rotating electric field. Directionally circular motions of the Janus particle
      following or countering the direction of the rotating electric field are observed
      in the low-frequency region (from 1 to 6 kHz) depending on the direction of
      electrorotation. In the higher frequency region (>10 kHz), only pure
      electrorotation and electrothermal flow are observed. By measuring the dependence
      of the frequency, voltage, and laser heating power, we propose that the
      tangential component of circular motion is caused by electric field enhanced self
      thermophoresis, which is proportional to the laser heating power and the electric
      field. This result indicates that thermophoresis could be modified by the induced
      zeta potential of the Janus particle tuned by the applied electric fields. By
      this mechanism, the intrinsic thermophoresis can be enhanced several times at a
      relatively low applied voltage (~3 Volt). Electrically tunable thermophoresis of
      a particle may bring new insights to thermophoresis phenomenon and also open a
      new direction for tunable active materials.

PMID- 29654241
TI  - Spin-dependent magneto-thermopower of narrow-gap lead chalcogenide quantum wells.
AB  - A semi-classical analysis of magneto-thermopower behaviour, namely, the Seebeck
      and Nernst effect (NE) in quantum wells of IV-VI lead salts with significant
      extrinsic Rashba spin-orbit coupling (RSOC) is performed in this report. In
      addition to the spin-dependent Seebeck effect that has been observed before, we
      also theoretically predict a similar spin-delineated behavior for its magneto
      thermal analog, the spin-dependent NE. The choice of lead salts follows from a
      two-fold advantage they offer, in part, to their superior thermoelectric
      properties, especially PbTe, while their low band gaps and high spin-orbit
      coupling make them ideal candidates to study RSOC governed effects in
      nanostructures. The calculations show a larger longitudinal magneto-thermopower
      for the spin-up electrons while the transverse components are nearly identical.
      In contrast, for a magnetic field free case, the related power factor
      calculations reveal a significantly higher contribution from the spin-down
      ensemble and suffer a reduction with an increase in the electron density. We also
      discuss qualitatively the limitations of the semi-classical approach for the
      extreme case of a high magnetic field and allude to the observed thermopower
      behaviour when the quantum Hall regime is operational. Finally, techniques to
      modulate the thermopower are briefly outlined.

PMID- 29654242
TI  - Water-stress induced downsizing of light-harvesting antenna complex protects
      developing rice seedlings from photo-oxidative damage.
AB  - The impact of water-stress on chloroplast development was studied by applying
      polyethylene glycol 6000 to the roots of 5-day-old etiolated rice (Oryza sativa)
      seedlings that were subsequently illuminated up to 72 h. Chloroplast development
      in drought environment led to down-regulation of light-harvesting Chl-proteins.
      Photosynthetic proteins of Photosystem II (PSII) and oxygen evolving complex
      i.e., Cytb559, OEC16, OEC23 and OEC33 as well as those of PSI such as PSI-III,
      PSI-V, and PSI-VI, decreased in abundance. Consequently, due to reduced light
      absorption by antennae, the electron transport rates of PSII and PSI decreased by
      55% and 25% respectively. Further, seedling development in stress condition led
      to a decline in the ratio of variable (Fv) to maximum (Fm) Chl a fluorescence, as
      well in the quantum yield of PSII photochemistry. Addition of Mg2+ to the
      thylakoid membranes suggested that Mg2+-induced grana stacking was not affected
      by water deficit. Proteomic analysis revealed the down-regulation of proteins
      involved in electron transport and in carbon reduction reactions, and up
      regulation of antioxidative enzymes. Our results demonstrate that developing
      seedlings under water deficit could downsize their light-harvesting capacity and
      components of photosynthetic apparatus to prevent photo-oxidative stress, excess
      ROS generation and membrane lipid peroxidation.

PMID- 29654243
TI  - Annealing induced atomic rearrangements on (Ga,In) (N,As) probed by hard X-ray
      photoelectron spectroscopy and X-ray absorption fine structure.
AB  - We study the effects of annealing on (Ga0.64,In0.36) (N0.045,As0.955) using hard
      X-ray photoelectron spectroscopy and X-ray absorption fine structure
      measurements. We observed surface oxidation and termination of the N-As bond
      defects caused by the annealing process. Specifically, we observed a
      characteristic chemical shift towards lower binding energies in the photoelectron
      spectra related to In. This phenomenon appears to be caused by the atomic
      arrangement, which produces increased In-N bond configurations within the matrix,
      as indicated by the X-ray absorption fine structure measurements. The reduction
      in the binding energies of group-III In, which occurs concomitantly with the
      atomic rearrangements of the matrix, causes the differences in the electronic
      properties of the system before and after annealing.

PMID- 29654245
TI  - Publisher Correction: Virtual Genome Walking across the 32 Gb Ambystoma mexicanum
      genome; assembling gene models and intronic sequence.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 29654244
TI  - Pretreatment rate of decay in forced vital capacity predicts long-term response
      to pirfenidone in patients with idiopathic pulmonary fibrosis.
AB  - Pirfenidone reduces functional decline in patients with Idiopathic Pulmonary
      Fibrosis (IPF). However, response to treatment is highly heterogeneous. We sought
      to evaluate whether response to pirfenidone is influenced by the pretreatment
      rate of forced vital capacity (FVC) decline. Fifty-six IPF patients were
      categorized as rapid (RP) or slow progressors (SP) based on whether their FVC
      decline in the year preceding pirfenidone treatment was > or <= 10% predicted.
      Following pirfenidone treatment patients were followed-up every 6 months and up
      to 24 months. In the entire population, pirfenidone reduced significantly FVC
      decline from 231 to 49 ml/year at 6 months (T6) (p = 0.003) and this effect was
      maintained at the 12-, 18- and 24-month time points (p value for trend n.s.). In
      RP, the reduction of FVC decline was evident at 6 months (36 vs 706 ml/year
      pretreatment; p = 0.002) and maintained, though to a lesser degree, at 12 (106
      ml/year), 18 (176 ml/year) and 24 months (162 ml/year; p value for trend n.s).
      Among SP, the reduction in FVC decline was not significant at any of the time
      points analyzed. In conclusion, pirfenidone reduces FVC decline in IPF patients.
      However, its beneficial effect is more pronounced in patients with rapidly
      progressive disease.

PMID- 29654246
TI  - Hippophae rhamnoides as novel phytogenic feed additive for broiler chickens at
      high altitude cold desert.
AB  - Extremes of climate and hypobaric hypoxia cause poor growth performance in
      broiler chickens at high altitude. The present study examined the potential of
      Hippophae rhamnoides extract as phytogenic feed additive for broilers reared at
      3500 m above mean sea level (MSL). Higher content of phytomolecules were recorded
      during characterization of the extract. Immunomodulatory activity of extract was
      observed in chicken lymphocytes through in-vitro studies. Thereafter, for in vivo
      study, 105 day old Rhode Island Red (RIR) Cross-bred chicks were randomly
      distributed in to control and treatments T1, T2, T3, T4, T5, and T6 which were
      supplemented with H. rhamnoides aqueous extract along with basal diet, at level
      of 100, 150, 200, 300, 400, and 800 mg/kg body weight of chicken, respectively.
      Among the experimental groups, birds in the T3 group represent the highest body
      weight. Furthermore, treatment group birds had shown better physio-biochemical
      indices as compared to control group birds. Interestingly, lower mortality rate
      due to ascites and coccidiosis was recorded in treatment groups and therefore,
      higher net return was observed. Hence, present investigation demonstrated the
      beneficial effect of H. rhamnoides extract (@200 mg/kg) at high altitude and
      therefore, may be used in formulation of feed additive for poultry ration.

PMID- 29654247
TI  - The revving up of CARs.

PMID- 29654248
TI  - Detection and characterisation of coronaviruses in migratory and non-migratory
      Australian wild birds.
AB  - We evaluated the presence of coronaviruses by PCR in 918 Australian wild bird
      samples collected during 2016-17. Coronaviruses were detected in 141 samples
      (15.3%) from species of ducks, shorebirds and herons and from multiple sampling
      locations. Sequencing of selected positive samples found mainly
      gammacoronaviruses, but also some deltacoronaviruses. The detection rate of
      coronaviruses was improved by using multiple PCR assays, as no single assay could
      detect all coronavirus positive samples. Sequencing of the relatively conserved
      Orf1 PCR amplicons found that Australian duck gammacoronaviruses were similar to
      duck gammacoronaviruses around the world. Some sequenced shorebird
      gammacoronaviruses belonged to Charadriiformes lineages, but others were more
      closely related to duck gammacoronaviruses. Australian duck and heron
      deltacoronaviruses belonged to lineages with other duck and heron
      deltacoronaviruses, but were almost 20% different in nucleotide sequence to other
      deltacoronavirus sequences available. Deltacoronavirus sequences from shorebirds
      formed a lineage with a deltacoronavirus from a ruddy turnstone detected in the
      United States. Given that Australian duck gammacoronaviruses are highly similar
      to those found in other regions, and Australian ducks rarely come into contact
      with migratory Palearctic duck species, we hypothesise that migratory shorebirds
      are the important vector for moving wild bird coronaviruses into and out of
      Australia.

PMID- 29654249
TI  - Treatment of adolescent obesity.
AB  - The increased prevalence of adolescent obesity and associated short-term and long
      term complications emphasize the need for effective treatment. In this Review, we
      aim to describe the evidence for, and elements of, behaviour management and
      adjunctive therapies and highlight the opportunities and challenges presented by
      obesity management in adolescence. The broad principles of treatment include
      management of obesity-associated complications; a developmentally appropriate
      approach; long-term behaviour modification (dietary change, increased physical
      activity, decreased sedentary behaviours and improved sleep patterns); long-term
      weight maintenance strategies; and consideration of the use of pharmacotherapy,
      more intensive dietary therapies and bariatric surgery. Bariatric surgery should
      be considered in those with severe obesity and be undertaken by skilled bariatric
      surgeons affiliated with teams experienced in the medical and psychosocial
      management of adolescents. Adolescent obesity management strategies are more
      reliant on active participation than those for childhood obesity and should
      recognize the emerging autonomy of the patient. The challenges in adolescent
      obesity relate primarily to the often competing demands of developing autonomy
      and not yet having attained neurocognitive maturity.

PMID- 29654250
TI  - Cystoid edema, neovascularization and inflammatory processes in the murine Norrin
      deficient retina.
AB  - Mutations in the Norrin (NDP) gene cause severe developmental blood vessel
      defects in the retina leading to congenital blindness. In the retina of Ndph
      knockout mice only the superficial capillary network develops. Here, a detailed
      characterization of this mouse model at late stages of the disease using in vivo
      retinal imaging revealed cystoid structures that closely resemble the ovoid cysts
      in the inner nuclear layer of the human retina with cystoid macular edema (CME).
      In human CME an involvement of Muller glia cells is hypothesized. In Ndph
      knockout retinae we could demonstrate that activated Muller cells were located
      around and within these cystoid spaces. In addition, we observed extensive
      activation of retinal microglia and development of neovascularization.
      Furthermore, ex vivo analyses detected extravasation of monocytic cells
      suggesting a breakdown of the blood retina barrier. Thus, we could demonstrate
      that also in the developmental retinal vascular pathology present in the Ndph
      knockout mouse inflammatory processes are active and may contribute to further
      retinal degeneration. This observation delivers a new perspective for curative
      treatments of retinal vasculopathies. Modulation of inflammatory responses might
      reduce the symptoms and improve visual acuity in these diseases.

PMID- 29654251
TI  - Deciphering the mechanism of action of 089, a compound impairing the fungal cell
      cycle.
AB  - Fungal infections represent an increasingly relevant clinical problem, primarily
      because of the increased survival of severely immune-compromised patients.
      Despite the availability of active and selective drugs and of well-established
      prophylaxis, classical antifungals are often ineffective as resistance is
      frequently observed. The quest for anti-fungal drugs with novel mechanisms of
      action is thus important. Here we show that a new compound, 089, acts by
      arresting fungal cells in the G2 phase of the cell cycle through targeting of
      SWE1, a mechanism of action unexploited by current anti-fungal drugs. The cell
      cycle impairment also induces a modification of fungal cell morphology which
      makes fungal cells recognizable by immune cells. This new class of molecules
      holds promise to be a valuable source of novel antifungals, allowing the
      clearance of pathogenic fungi by both direct killing of the fungus and enhancing
      the recognition of the pathogen by the host immune system.

PMID- 29654252
TI  - Low serum levels of vitamin D are associated with anxiety in children and
      adolescents with dialysis.
AB  - Anxiety is a frequent and serious complication of children and adolescents
      receiving dialysis. Low serum vitamin D levels have been associated with anxiety
      in non-pediatric patients. This study sought to examine the possible association
      between serum vitamin D levels and the presence of anxiety in children and
      adolescents with dialysis in China. A total of 156 pediatric patients who were on
      hemodialysis or peritoneal dialysis and 100 healthy controls were included in the
      current study. Serum 25-hydroxyvitamin D [25(OH)D] levels were measured by using
      a competitive protein-binding assay. Anxiety was assessed by using the Chinese
      version of the Screen for Child Anxiety Related Emotional Disorders (SCARED, = 25
      as cutoff). Among 156 patients, 110 had a current anxiety (70.5%) and 46 did not
      (29.5%). Serum levels of 25(OH)D were significantly lower in patients with
      anxiety than in normal controls (19.4 +/- 10.3 vs. 38.6 +/- 15.5 ng/ml, P <
      0.001). Serum 25(OH)D levels (<=15.0 ng/ml) were independently associated with
      the existent of anxiety in children and adolescents receiving dialysis (OR 4.650,
      95% CI 1.663-13.001, P = 0.003). Our research demonstrates that low serum levels
      of vitamin D are independently associated with anxiety among children and
      adolescents on dialysis, which needs to be confirmed in future experimental and
      clinical studies.

PMID- 29654253
TI  - Morphological characterization of NG2 glia and their association with neuroglial
      cells in the 3-nitropropionic acid-lesioned striatum of rat.
AB  - Our aim was to examine the spatiotemporal profiles and phenotypic characteristics
      of neuron-glia antigen 2 (NG2) glia and their associations with neuroglial cells
      in striatal lesions due to the mitochondrial toxin 3-nitropropionic acid (3-NP).
      In control striatum, weak NG2 immunoreactivity was restricted to resting NG2 glia
      with thin processes, but prominent NG2 expression was noted on activated
      microglia/macrophages, and reactive NG2 glia in the lesion core after 3-NP
      injection. Activation of NG2 glia, including enhanced proliferation and
      morphological changes, had a close spatiotemporal relationship with infiltration
      of activated microglia into the lesion core. Thick and highly branched processes
      of reactive NG2 glia formed a cellular network in the astrocyte-free lesion core
      and primarily surrounded developing cavities 2-4 weeks post-lesion. NG2 glia
      became associated with astrocytes in the lesion core and the border of cavities
      over the chronic interval of 4-8 weeks. Immunoelectron microscopy indicated that
      reactive NG2 glia had large euchromatic nuclei with prominent nucleoli and thick
      and branched processes that ramified distally. Thus, our data provide detailed
      information regarding the morphologies of NG2 glia in the lesion core, and
      support the link between transformation of NG2 glia to the reactive form and
      microglial activation/recruitment in response to brain insults.

PMID- 29654254
TI  - Spoof Surface Plasmon Polaritons Power Divider with large Isolation.
AB  - Periodic corrugated metal structure is designed to support and propagate spoof
      surface plasmon polaritons (SSPPs) wave in the microwave frequencies. In this
      paper, firstly a plasmonic waveguide consisting of oval-ring shaped cells is
      proposed with the performance of high transmission efficiency in a wide frequency
      range. The coplanar waveguides (CPWs) with 50 Omega impedance are adopted to feed
      the energies or extract signals at both ends of the plasmonic waveguide. Then a
      well-isolated power divider is constructed based on the SSPPs waveguides aiming
      to equally split the energy of the SSPPs wave into two equal parts. The stepped
      impedances are co-designed with the three input/output ports of the power divider
      to achieve the impedance-matching between the SSPPs waveguides and the coplanar
      waveguides. Besides, a single resistor is placed in the middle of two symmetrical
      half oval-rings to realize the isolation between the two output ports over the
      spectrum of 4.5-7.5 GHz. Finally, both plasmonic waveguide and the power divider
      are fabricated and tested to verify the predicted characteristics.

PMID- 29654255
TI  - Reflection from a free carrier front via an intraband indirect photonic
      transition.
AB  - The reflection of light from moving boundaries is of interest both fundamentally
      and for applications in frequency conversion, but typically requires high pump
      power. By using a dispersion-engineered silicon photonic crystal waveguide, we
      are able to achieve a propagating free carrier front with only a moderate on-chip
      peak power of 6 W in a 6 ps-long pump pulse. We employ an intraband indirect
      photonic transition of a co-propagating probe, whereby the probe practically
      escapes from the front in the forward direction. This forward reflection has up
      to 35% efficiency and it is accompanied by a strong frequency upshift, which
      significantly exceeds that expected from the refractive index change and which is
      a function of group velocity, waveguide dispersion and pump power. Pump, probe
      and shifted probe all are around 1.5 um wavelength which opens new possibilities
      for "on-chip" frequency manipulation and all-optical switching in optical
      telecommunications.

PMID- 29654256
TI  - Influence of urban and transport planning and the city environment on
      cardiovascular disease.
AB  - This Review describes the relationship between urban and transport planning and
      the city environment, the main cardiovascular risk factors (including physical
      activity, hypertension, and obesity), and cardiovascular disease and mortality.
      Good evidence exists for a relationship between built environment measures (such
      as mixed land use, connectivity and walkability, and physical activity),
      environmental exposures (such as green space, air pollution, and noise), and
      cardiovascular disease and mortality. Some good evidence exists for a link
      between transport mode and cardiovascular disease, but evidence is inconsistent
      for an association between built environment measures and weight status, and
      between green space and either weight status or physical activity. Further
      research is needed into the influence of built environment measures on
      cardiovascular disease and mortality. Urban and transport planning has an
      important effect on cardiovascular health and its risk factors. Cardiovascular
      disease and mortality could be reduced by better urban and transport planning
      that promotes physical activity; reduces levels of air pollution, noise, and heat
      island effects; and increases green space.

PMID- 29654257
TI  - Revascularization in stable coronary disease: evidence and uncertainties.
AB  - Although revascularization has been one of the primary treatment options for
      obstructive coronary artery disease (CAD) for about 50 years, the evidence base
      for its use is most robust in the area of acute coronary disease. By contrast,
      evidence - particularly from clinical trials - supporting the use of
      revascularization to improve clinical outcomes in stable CAD is in some important
      respects outdated in that it reflects therapies that predate both contemporary
      standards for optimal medical therapy and current revascularization techniques
      and technologies. Despite such limitations, these clinical trials still provide
      the foundation for many of the current guideline-based indications for coronary
      revascularization in patients with stable CAD. In this Review, we discuss the
      major factors underlying the clinical decision to perform revascularization in
      patients with stable CAD and examine the use and limitations of existing evidence
      on the choice for, and preferred methods of, revascularization, namely, CABG
      surgery versus percutaneous coronary intervention.

PMID- 29654258
TI  - Increasing salinity drastically reduces hatching success of crustaceans from
      depression wetlands of the semi-arid Eastern Cape Karoo region, South Africa.
AB  - Salinity is an important factor affecting freshwater aquatic species distribution
      and diversity. The semi-arid Eastern Cape Karoo region of South Africa has been
      earmarked for shale gas development through hydraulic fracturing. The process
      uses large amounts of water and produces briny wastewater. When not managed
      properly, these wastewaters may lead to salinisation of surface freshwater bodies
      in the region. Therefore, the effect of salinity on the hatching success of
      crustacean resting eggs was examined using sediments from four depression
      wetlands found in the region. The sediments were exposed for 28 days to salinity
      levels of 0.5 g L-1, 2.5 g L-1, 5 g L-1 and 10 g L-1. Control aquaria in which no
      salt was added were also set up. There was a significant decrease in the emerged
      taxa richness and abundances at salinities of 2.5 g L-1 and above. Anostraca,
      Notostraca and Spinicaudata hatchlings were abundant at salinities of 0.5 g L-1
      and below, while Copepoda, Daphniidae (Cladocera) and Ostracoda were observed in
      the highest salinity, but their densities were still lower with increased
      salinities. Given the importance of large branchiopods in the trophic balance of
      depression wetlands, their loss may alter the ecological balance and function of
      these ecosystems.

PMID- 29654259
TI  - mGlu1 and mGlu5 modulate distinct excitatory inputs to the nucleus accumbens
      shell.
AB  - Glutamatergic transmission in the nucleus accumbens shell (NAcSh) is a substrate
      for reward learning and motivation. Metabotropic glutamate (mGlu) receptors
      regulate NAcSh synaptic strength by inducing long-term depression (LTD). Inputs
      from prefrontal cortex (PFC) and medio-dorsal thalamus (MDT) drive opposing
      motivated behaviors yet mGlu receptor regulation of these synapses is unexplored.
      We examined Group I mGlu receptor regulation of PFC and MDT glutamatergic
      synapses onto specific populations of NAc medium spiny neurons (MSNs) using
      D1tdTom BAC transgenic mice and optogenetics. Synaptically evoked long-term
      depression (LTD) at MDT-NAcSh synapses required mGlu5 but not mGlu1 and was
      specific for D1(+) MSNs, whereas PFC LTD was expressed at both D1(+) and D1(-)
      MSNs and required mGlu1 but not mGlu5. Two weeks after five daily non-contingent
      cocaine exposures (15 mg/kg), LTD was attenuated at MDT-D1(+) synapses but was
      rescued by the mGlu5-positive allosteric modulator (PAM) VU0409551. These results
      highlight unique plasticity mechanisms regulating specific NAcSh synapses.

PMID- 29654260
TI  - Medial septum differentially regulates dopamine neuron activity in the rat
      ventral tegmental area and substantia nigra via distinct pathways.
AB  - The medial septum (MS) impacts hippocampal activity and the hippocampus, in turn,
      regulates midbrain dopamine (DA) neuron activity. However, it remains to be
      determined how MS activation impacts midbrain DA activity. This question was
      addressed by infusing NMDA (0.75 ug/0.2 uL) into the medial septum of
      anesthetized male Sprague-Dawley rats and recording dopamine neuron activity in
      the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc). MS
      activation increased (71%) the number of spontaneously active DA neurons in the
      VTA, and decreased (40%) the number of active DA neurons in the SNc. Effects in
      both the VTA and SNc required the ventral subiculum, but were differentially
      dependent on cholinergic and GABAergic mechanisms within the vSub and rostral and
      caudal subregions of the ventral pallidum, respectively. MS activation also
      decreased amphetamine-induced locomotor behavior, which was dependent on
      GABAergic inputs to the hippocampus. These findings demonstrate that the MS
      differentially regulates meso-striatal DA transmission via distinct pathways.

PMID- 29654261
TI  - A fast and cost-effective method for apolipoprotein E isotyping as an alternative
      to APOE genotyping for patient screening and stratification.
AB  - Apolipoprotein E (apoE) is a 34 kDa glycoprotein involved in lipid metabolism.
      The human APOE gene encodes for three different apoE protein isoforms: E2, E3 and
      E4. The interest in apoE isoforms is high for epidemiological research, patient
      stratification and identification of those at increased risk for clinical trials
      and prevention. The isoform apoE4 is associated with increased risk for coronary
      heart and Alzheimer's diseases. This paper describes a method for specifically
      detecting the apoE4 isoform from biological fluids by taking advantage of the
      capacity of apoE to bind "specifically" to polystyrene surfaces as capture and a
      specific anti-apoE4 monoclonal antibody as reporter. Our results indicate that
      the apoE-polystyrene binding interaction is highly stable, resistant to
      detergents and acid and basic washes. The methodology here described is accurate,
      easily implementable, fast and cost-effective. Although at present, our technique
      is unable to discriminate homozygous APOE epsilon4/epsilon4 from APOE
      epsilon3/epsilon4 and epsilon2/epsilon4 heterozygous, it opens new avenues for
      the development of inexpensive, yet effective, tests for the detection of apoE4
      for patients' stratification. Preliminary results indicated that this methodology
      is also adaptable into turbidimetric platforms, which make it a good candidate
      for clinical implementation through its translation to the clinical analysis
      routine.

PMID- 29654262
TI  - Continuous-variable protocol for oblivious transfer in the noisy-storage model.
AB  - Cryptographic protocols are the backbone of our information society. This
      includes two-party protocols which offer protection against distrustful players.
      Such protocols can be built from a basic primitive called oblivious transfer. We
      present and experimentally demonstrate here a quantum protocol for oblivious
      transfer for optical continuous-variable systems, and prove its security in the
      noisy-storage model. This model allows us to establish security by sending more
      quantum signals than an attacker can reliably store during the protocol. The
      security proof is based on uncertainty relations which we derive for continuous
      variable systems, that differ from the ones used in quantum key distribution. We
      experimentally demonstrate in a proof-of-principle experiment the proposed
      oblivious transfer protocol for various channel losses by using entangled two
      mode squeezed states measured with balanced homodyne detection. Our work enables
      the implementation of arbitrary two-party quantum cryptographic protocols with
      continuous-variable communication systems.

PMID- 29654264
TI  - Treatment approaches and outcomes in plasmacytomas: analysis using a national
      dataset.
AB  - Solitary plasmacytomas are uncommon plasma cell disorders, which may present as a
      single bone lesion (P-bone) or extramedullary plasmacytoma (P-EM). There is a
      paucity of large studies analyzing prognostic factors and outcomes of
      plasmacytomas. While the treatment of choice is radiation therapy (RT), there is
      a lack of data evaluating optimal RT dose. In this study, we sought to answer
      these questions by utilizing the National Cancer Database plasmacytoma data from
      2000 to 2011. A total of 5056 patients were included in the study (median age 62
      years; range 52-72). To obtain a pure plasmacytoma cohort, potential multiple
      myeloma patients were excluded from the study (bone marrow involvement, systemic
      chemotherapy use). P-bone constituted 70% of the patients. The median overall
      survival (OS) of P-EM was significantly longer than P-bone (132 vs. 85 months),
      and for soft/connective tissue it was worse than remainder of P-EM (82 vs. 148
      months). On multivariable analysis, factors associated with worse OS included
      older age (>=65), presence of P-bone, and treatment with a radiation dose <40 Gy.

PMID- 29654263
TI  - Hedgehog pathway mutations drive oncogenic transformation in high-risk T-cell
      acute lymphoblastic leukemia.
AB  - The role of Hedgehog signaling in normal and malignant T-cell development is
      controversial. Recently, Hedgehog pathway mutations have been described in T-ALL,
      but whether mutational activation of Hedgehog signaling drives T-cell
      transformation is unknown, hindering the rationale for therapeutic intervention.
      Here, we show that Hedgehog pathway mutations predict chemotherapy resistance in
      human T-ALL, and drive oncogenic transformation in a zebrafish model of the
      disease. We found Hedgehog pathway mutations in 16% of 109 childhood T-ALL cases,
      most commonly affecting its negative regulator PTCH1. Hedgehog mutations were
      associated with resistance to induction chemotherapy (P = 0.009). Transduction of
      wild-type PTCH1 into PTCH1-mutant T-ALL cells induced apoptosis (P = 0.005), a
      phenotype that was reversed by downstream Hedgehog pathway activation (P =
      0.007). Transduction of most mutant PTCH1, SUFU, and GLI alleles into mammalian
      cells induced aberrant regulation of Hedgehog signaling, indicating that these
      mutations are pathogenic. Using a CRISPR/Cas9 system for lineage-restricted gene
      disruption in transgenic zebrafish, we found that ptch1 mutations accelerated the
      onset of notch1-induced T-ALL (P = 0.0001), and pharmacologic Hedgehog pathway
      inhibition had therapeutic activity. Thus, Hedgehog-activating mutations are
      driver oncogenic alterations in high-risk T-ALL, providing a molecular rationale
      for targeted therapy in this disease.

PMID- 29654265
TI  - RET-mediated autophagy suppression as targetable co-dependence in acute myeloid
      leukemia.
AB  - Many cases of AML are associated with mutational activation of receptor tyrosine
      kinases (RTKs) such as FLT3. However, RTK inhibitors have limited clinical
      efficacy as single agents, indicating that AML is driven by concomitant
      activation of different signaling molecules. We used a functional genomic
      approach to identify RET, encoding an RTK, as an essential gene in multiple
      subtypes of AML, and observed that AML cells show activation of RET signaling via
      ARTN/GFRA3 and NRTN/GFRA2 ligand/co-receptor complexes. Interrogation of
      downstream pathways identified mTORC1-mediated suppression of autophagy and
      subsequent stabilization of leukemogenic drivers such as mutant FLT3 as important
      RET effectors. Accordingly, genetic or pharmacologic RET inhibition impaired the
      growth of FLT3-dependent AML cell lines and was accompanied by upregulation of
      autophagy and FLT3 depletion. RET dependence was also evident in mouse models of
      AML and primary AML patient samples, and transcriptome and immunohistochemistry
      analyses identified elevated RET mRNA levels and co-expression of RET and FLT3
      proteins in a substantial proportion of AML patients. Our results indicate that
      RET-mTORC1 signaling promotes AML through autophagy suppression, suggesting that
      targeting RET or, more broadly, depletion of leukemogenic drivers via autophagy
      induction provides a therapeutic opportunity in a relevant subset of AML
      patients.

PMID- 29654266
TI  - Clinical use of lentiviral vectors.
AB  - Viral vectors provide an efficient means for modification of eukaryotic cells,
      and their use is now commonplace in academic laboratories and industry for both
      research and clinical gene therapy applications. Lentiviral vectors, derived from
      the human immunodeficiency virus, have been extensively investigated and
      optimized over the past two decades. Third-generation, self-inactivating
      lentiviral vectors have recently been used in multiple clinical trials to
      introduce genes into hematopoietic stem cells to correct primary
      immunodeficiencies and hemoglobinopathies. These vectors have also been used to
      introduce genes into mature T cells to generate immunity to cancer through the
      delivery of chimeric antigen receptors (CARs) or cloned T-cell receptors. CAR T
      cell therapies engineered using lentiviral vectors have demonstrated noteworthy
      clinical success in patients with B-cell malignancies leading to regulatory
      approval of the first genetically engineered cellular therapy using lentiviral
      vectors. In this review, we discuss several aspects of lentiviral vectors that
      will be of interest to clinicians, including an overview of lentiviral vector
      development, the current uses of viral vectors as therapy for primary
      immunodeficiencies and cancers, large-scale manufacturing of lentiviral vectors,
      and long-term follow-up of patients treated with gene therapy products.

PMID- 29654268
TI  - Revisiting thrombocytopenia in acute promyelocytic leukemia.

PMID- 29654267
TI  - GIPSS: genetically inspired prognostic scoring system for primary myelofibrosis.
AB  - International collaborations over the years have produced a series of prognostic
      models for primary myelofibrosis (PMF), including the recently unveiled mutation
      enhanced international prognostic scoring systems for transplant-age patients
      (MIPSS70 and MIPSS70-plus). In the current study, we considered the feasibility
      of a genetically inspired prognostic scoring system (GIPSS) that is exclusively
      based on genetic markers. Among 641 cytogenetically annotated patients with PMF
      and informative for previously recognized adverse mutations, multivariable
      analysis identified "VHR" karyotype, "unfavorable" karyotype, absence of type
      1/like CALR mutation and presence of ASXL1, SRSF2, or U2AF1Q157 mutation, as
      inter-independent predictors of inferior survival; the respective HRs (95% CI)
      were 3.1 (2.1-4.3), 2.1 (1.6-2.7), 2.1 (1.6-2.9), 1.8 (1.5-2.3), 2.4 (1.9-3.2),
      and 2.4 (1.7-3.3). Based on HR-weighted risk points, a four-tiered GIPSS model
      was devised: low (zero points; n = 58), intermediate-1 (1 point; n = 260),
      intermediate-2 (2 points; n = 192), and high (>=3 points; n = 131); the
      respective median (5-year) survivals were 26.4 (94%), 8.0 (73%), 4.2 (40%), and 2
      (14%) years; the model was internally validated by bootstrapping and its
      predictive accuracy was shown to be comparable to that of MIPSS70-plus. GIPPS
      offers a low-complexity prognostic tool for PMF that is solely dependent on
      genetic risk factors and, thus, forward-looking in its essence.

PMID- 29654269
TI  - Kinase domain activation through gene rearrangement in multiple myeloma.
AB  - Chromosomal rearrangements that result in oncogenic kinase activation are present
      in many solid and hematological malignancies, but none have been reported in
      multiple myeloma (MM). Here we analyzed 1421 samples from 958 myeloma patients
      using a targeted assay and detected fusion genes in 1.5% of patients. These
      fusion genes were in-frame and the majority of them contained kinase domains from
      either receptor tyrosine kinases (ALK, ROS1, NTRK3, and FGFR1) or cytoplasmic
      kinases (BRAF, MAP3K14, and MAPK14), which would result in the activation of
      MEK/ERK, NF-kappaB, or inflammatory signaling pathways. Fusion genes were present
      in smoldering MM, newly diagnosed MM, and relapse patient samples indicating they
      are not solely late events. Most fusion genes were subclonal in nature, but one
      EML4-ALK fusion was clonal indicating it is a driver of disease pathogenesis.
      Samples with fusions of receptor tyrosine kinases were not found in conjunction
      with clonal Ras/Raf mutations indicating a parallel mechanism of MEK/ERK pathway
      activation. Fusion genes involving MAP3K14 (NIK), which regulates the NF-kappaB
      pathway, were detected as were t(14;17) rearrangements involving NIK in 2% of MM
      samples. Activation of kinases in myeloma through rearrangements presents an
      opportunity to use treatments existing in other cancers.

PMID- 29654270
TI  - Patients with low OCT-1 activity and high ABCB1 fold rise have poor long-term
      outcomes in response to tyrosine kinase inhibitor therapy.

PMID- 29654272
TI  - Identification of novel lncRNAs regulated by the TAL1 complex in T-cell acute
      lymphoblastic leukemia.
AB  - TAL1/SCL is one of the most prevalent oncogenes in T-cell acute lymphoblastic
      leukemia (T-ALL). TAL1 and its regulatory partners (GATA3, RUNX1, and MYB)
      positively regulate each other and coordinately regulate the expression of their
      downstream target genes in T-ALL cells. However, long non-coding RNAs (lncRNAs)
      regulated by these factors are largely unknown. Here we established a
      bioinformatics pipeline and analyzed RNA-seq datasets with deep coverage to
      identify lncRNAs regulated by TAL1 in T-ALL cells. Our analysis predicted 57
      putative lncRNAs that are activated by TAL1. Many of these transcripts were
      regulated by GATA3, RUNX1, and MYB in a coordinated manner. We identified two
      novel transcripts that were activated in multiple T-ALL cell samples but were
      downregulated in normal thymocytes. One transcript near the ARID5B gene locus was
      specifically expressed in TAL1-positive T-ALL cases. The other transcript located
      between the FAM49A and MYCN gene locus was also expressed in normal hematopoietic
      stem cells and T-cell progenitor cells. In addition, we identified a subset of
      lncRNAs that were negatively regulated by TAL1 and positively regulated by E
      proteins in T-ALL cells. This included a known lncRNA (lnc-OAZ3-2:7) located near
      the RORC gene, which was expressed in normal thymocytes but repressed in TAL1
      positive T-ALL cells.

PMID- 29654271
TI  - Whole-genome sequencing of multiple myeloma reveals oncogenic pathways are
      targeted somatically through multiple mechanisms.
AB  - Multiple myeloma (MM) is a biologically heterogeneous malignancy, however, the
      mechanisms underlying this complexity are incompletely understood. We report an
      analysis of the whole-genome sequencing of 765 MM patients from CoMMpass. By
      employing promoter capture Hi-C in naive B-cells, we identify cis-regulatory
      elements (CREs) that represent a highly enriched subset of the non-coding genome
      in which to search for driver mutations. We identify regulatory regions whose
      mutation significantly alters the expression of genes as candidate non-coding
      drivers, including copy number variation (CNV) at CREs of MYC and single
      nucleotide variants (SNVs) in a PAX5 enhancer. To better inform the interplay
      between non-coding driver mutations with other driver mechanisms, and their
      respective roles in oncogenic pathways, we extended our analysis identifying
      coding drivers in 40 genes, including 11 novel candidates. We demonstrate the
      same pathways can be targeted by coding and non-coding mutations; exemplified by
      IRF4 and PRDM1, along with BCL6 and PAX5, genes that are central to plasma cell
      differentiation. This study reveals new insights into the complex genetic
      alterations driving MM development and an enhanced understanding of oncogenic
      pathways.

PMID- 29654273
TI  - YAP and TAZ are dispensable for physiological and malignant haematopoiesis.

PMID- 29654274
TI  - Lenalidomide enhances MOR202-dependent macrophage-mediated effector functions via
      the vitamin D pathway.
AB  - Macrophages are key mediators of the therapeutic effects exerted by monoclonal
      antibodies, such as the anti-CD38 antibody MOR202, currently introduced in
      multiple myeloma (MM) therapy. Therefore, it is important to understand how
      antibody-mediated effector functions of myeloma-associated macrophages (MAMs) are
      regulated. Here, we focused on the effects of vitamin D, a known regulator of
      macrophage effector functions. Consequently, it was the aim of this study to
      assess whether modulation of the vitamin D pathway alters the tumoricidal
      activity of MAMs. Here, we demonstrate that MAMs display a defective vitamin D
      pathway with reduced expression level of CYP27B1 and limited tumoricidal activity
      which can be restored by the IMiD lenalidomide in vitro. Furthermore, our data
      indicate that the vitamin D pathway of MAMs from MM patients does recover during
      an IMiD-containing therapy shown by an improved MOR202-mediated cytotoxic
      activity of these MAMs against primary MM cells ex vivo. Here, the ex vivo
      cytotoxic activity could be further enhanced by vitamin D supplementation. These
      data suggest that vitamin D holds a key role for the effector functions of MAMs
      and that vitamin D supplementation in IMiD combination trials could further
      increase the therapeutic efficacy of anti-CD38 antibodies such as MOR202, which
      remains to be investigated in clinical studies.

PMID- 29654275
TI  - Role of the Interplay Between the Internal and External Conditions in Invasive
      Behavior of Tumors.
AB  - Tumor growth, which plays a central role in cancer evolution, depends on both the
      internal features of the cells, such as their ability for unlimited duplication,
      and the external conditions, e.g., supply of nutrients, as well as the dynamic
      interactions between the two. A stem cell theory of cancer has recently been
      developed that suggests the existence of a subpopulation of self-renewing tumor
      cells to be responsible for tumorigenesis, and is able to initiate metastatic
      spreading. The question of abundance of the cancer stem cells (CSCs) and its
      relation to tumor malignancy has, however, remained an unsolved problem and has
      been a subject of recent debates. In this paper we propose a novel model beyond
      the standard stochastic models of tumor development, in order to explore the
      effect of the density of the CSCs and oxygen on the tumor's invasive behavior.
      The model identifies natural selection as the underlying process for complex
      morphology of tumors, which has been observed experimentally, and indicates that
      their invasive behavior depends on both the number of the CSCs and the oxygen
      density in the microenvironment. The interplay between the external and internal
      conditions may pave the way for a new cancer therapy.

PMID- 29654276
TI  - Community Detection in Complex Networks via Clique Conductance.
AB  - Network science plays a central role in understanding and modeling complex
      systems in many areas including physics, sociology, biology, computer science,
      economics, politics, and neuroscience. One of the most important features of
      networks is community structure, i.e., clustering of nodes that are locally
      densely interconnected. Communities reveal the hierarchical organization of
      nodes, and detecting communities is of great importance in the study of complex
      systems. Most existing community-detection methods consider low-order connection
      patterns at the level of individual links. But high-order connection patterns, at
      the level of small subnetworks, are generally not considered. In this paper, we
      develop a novel community-detection method based on cliques, i.e., local complete
      subnetworks. The proposed method overcomes the deficiencies of previous similar
      community-detection methods by considering the mathematical properties of
      cliques. We apply the proposed method to computer-generated graphs and real-world
      network datasets. When applied to networks with known community structure, the
      proposed method detects the structure with high fidelity and sensitivity. When
      applied to networks with no a priori information regarding community structure,
      the proposed method yields insightful results revealing the organization of these
      complex networks. We also show that the proposed method is guaranteed to detect
      near-optimal clusters in the bipartition case.

PMID- 29654277
TI  - Contribution of DA Signaling to Appetitive Odor Perception in a Drosophila Model.
AB  - Understanding cognitive processes that translate chemically diverse olfactory
      stimuli to specific appetitive drives remains challenging. We have shown that
      food-related odors arouse impulsive-like feeding of food media that are palatable
      and readily accessible in well-nourished Drosophila larvae. Here we provide
      evidence that two assemblies of four dopamine (DA) neurons, one per brain
      hemisphere, contribute to perceptual processing of the qualitative and
      quantitative attributes of food scents. These DA neurons receive neural
      representations of chemically diverse food-related odors, and their combined
      neuronal activities become increasingly important as the chemical complexity of
      an appetizing odor stimulus increases. Furthermore, in each assembly of DA
      neurons, integrated odor signals are transformed to one-dimensional DA outputs
      that have no intrinsic reward values. Finally, a genetic analysis has revealed a
      D1-type DA receptor (Dop1R1)-gated mechanism in neuropeptide Y-like neurons that
      assigns appetitive significance to selected DA outputs. Our findings suggest that
      fly larvae provide a useful platform for elucidation of molecular and circuit
      mechanisms underlying cognitive processing of olfactory and possibly other
      sensory cues.

PMID- 29654278
TI  - Identification of somatic mutations in monozygotic twins discordant for
      psychiatric disorders.
AB  - Monozygotic twins are assumed to have identical genomes. Based on this
      assumption, phenotypic discordance in monozygotic twins has been previously
      attributed to environmental factors. However, recent genomic studies have
      identified characteristic somatic mutations in monozygotic twins discordant for
      Darier disease, Van der Woude syndrome, and Dravet syndrome. Here, we explored
      somatic mutations in four pairs of monozygotic twins discordant for schizophrenia
      or delusional disorder. We analyzed whole exome sequence data obtained from blood
      samples and identified seven somatic mutations in one twin pair discordant for
      delusional disorder. All seven of these mutations were validated by independent
      amplicon sequencing, and five of them were further validated by pyrosequencing.
      One somatic mutation in the patient with delusional disorder showed a missense
      variant in ABCC9 with an allele fraction of 7.32%. Although an association
      between the somatic mutations and phenotypic discordance could not be established
      conclusively in this study, our results suggest that somatic mutations in
      monozygotic twins may contribute to the development of psychiatric disorders, and
      can serve as high-priority candidates for genetic studies.

PMID- 29654279
TI  - Horizontal antimicrobial resistance transfer drives epidemics of multiple
      Shigella species.
AB  - Horizontal gene transfer has played a role in developing the global public health
      crisis of antimicrobial resistance (AMR). However, the dynamics of AMR transfer
      through bacterial populations and its direct impact on human disease is poorly
      elucidated. Here, we study parallel epidemic emergences of multiple Shigella
      species, a priority AMR organism, in men who have sex with men to gain insight
      into AMR emergence and spread. Using genomic epidemiology, we show that repeated
      horizontal transfer of a single AMR plasmid among Shigella enhanced existing and
      facilitated new epidemics. These epidemic patterns contrasted with slighter,
      slower increases in disease caused by organisms with vertically inherited
      (chromosomally encoded) AMR. This demonstrates that horizontal transfer of AMR
      directly affects epidemiological outcomes of globally important AMR pathogens and
      highlights the need for integration of genomic analyses into all areas of AMR
      research, surveillance and management.

PMID- 29654280
TI  - Sign epistasis caused by hierarchy within signalling cascades.
AB  - Sign epistasis is a central evolutionary constraint, but its causal factors
      remain difficult to predict. Here we use the notion of parameterised optima to
      explain epistasis within a signalling cascade, and test these predictions in
      Escherichia coli. We show that sign epistasis arises from the benefit of tuning
      phenotypic parameters of cascade genes with respect to each other, rather than
      from their complex and incompletely known genetic bases. Specifically, sign
      epistasis requires only that the optimal phenotypic parameters of one gene depend
      on the phenotypic parameters of another, independent of other details, such as
      activating or repressing nature, position within the cascade, intra-genic
      pleiotropy or genotype. Mutational effects change sign more readily in downstream
      genes, indicating that optimising downstream genes is more constrained. The
      findings show that sign epistasis results from the inherent upstream-downstream
      hierarchy between signalling cascade genes, and can be addressed without
      exhaustive genotypic mapping.

PMID- 29654281
TI  - Co-exposure to benzo[a]pyrene and ethanol induces a pathological progression of
      liver steatosis in vitro and in vivo.
AB  - Hepatic steatosis (i.e. lipid accumulation) and steatohepatitis have been related
      to diverse etiologic factors, including alcohol, obesity, environmental
      pollutants. However, no study has so far analyzed how these different factors
      might interplay regarding the progression of liver diseases. The impact of the co
      exposure to the environmental carcinogen benzo[a]pyrene (B[a]P) and the lifestyle
      related hepatotoxicant ethanol, was thus tested on in vitro models of steatosis
      (human HepaRG cell line; hybrid human/rat WIF-B9 cell line), and on an in vivo
      model (obese zebrafish larvae). Steatosis was induced prior to chronic treatments
      (14, 5 or 7 days for HepaRG, WIF-B9 or zebrafish, respectively). Toxicity and
      inflammation were analyzed in all models; the impact of steatosis and ethanol
      towards B[a]P metabolism was studied in HepaRG cells. Cytotoxicity and expression
      of inflammation markers upon co-exposure were increased in all steatotic models,
      compared to non steatotic counterparts. A change of B[a]P metabolism with a
      decrease in detoxification was detected in HepaRG cells under these conditions. A
      prior steatosis therefore enhanced the toxicity of B[a]P/ethanol co-exposure in
      vitro and in vivo; such a co-exposure might favor the appearance of a
      steatohepatitis-like state, with the development of inflammation. These
      deleterious effects could be partly explained by B[a]P metabolism alterations.

PMID- 29654282
TI  - Traction table versus double reverse traction repositor in the treatment of
      femoral shaft fractures.
AB  - A novel reduction technique of intramedullary nailing (IMN) for femoral shaft
      fractures was introduced, and in this study, its therapeutic effect was compared
      with patients treated with the traditional traction table. From November 2012 to
      August 2015, the patients with femoral shaft fractures fixed with anterograde IMN
      were reviewed. Seventy-four patients treated with the traction table and forty
      eight patients treated with the double reverse traction repositor (DRTR) met the
      inclusion criteria of this study. The surgical time, blood loss, open reduction
      rate and complications were reviewed in this study. The fracture healing was
      assessed by the radiographs conducted at each follow-up. The functional outcome
      (hip and knee flexion, Harris Hip Score, and Lysholm knee score) was evaluated at
      the final follow-up. Average surgical time, blood loss, hip and knee flexion, and
      Harris Hip Score showed no difference (P > 0.05) between the two groups. However,
      the DRTR was superior to the traction table in fracture healing, Lysholm knee
      score, open reduction and complications rate (P < 0.05). Thus, we concluded that
      minimally invasive treatment of femoral shaft fractures could be obtained with
      the DRTR.

PMID- 29654283
TI  - Dynamic transcriptomic analysis of Ischemic Injury in a Porcine Pre-Clinical
      Model mimicking Donors Deceased after Circulatory Death.
AB  - Due to organ shortage, clinicians are prone to consider alternative type of organ
      donors among them donors deceased after circulatory death (DCD). However,
      especially using these organs which are more prone to graft dysfunction, there is
      a need to better understand mechanistic events ocuring during ischemia phase and
      leading to ischemia/reperfusion injuries (IRI). The aim of this study is to
      provide a dynamic transcriptomic analysis of preclinical porcine model kidneys
      subjected to ischemic stress mimicking DCD donor. We compared cortex and
      corticomedullary junction (CMJ) tissues from porcine kidneys submitted to 60 min
      warm ischemia (WI) followed by 0, 6 or 24 hours of cold storage in University of
      Wisconsin solution versus control non-ischemic kidneys (n = 5 per group). 29
      cortex genes and 113 CMJ genes were significantly up or down-regulated after WI
      versus healthy kidneys, and up to 400 genes were regulated after WI followed by 6
      or 24 hours of cold storage (p < 0.05). Functionnal enrichment analysis (home
      selected gene kinetic classification, Gene-ontology-biological processes and Gene
      ontology-molecular-function) revealed relevant genes implication during WI and
      cold storage. We uncovered targets which we will further validate as biomarkers
      and new therapeutic targets to optimize graft kidney quality before
      transplantation and improve whole transplantation outcome.

PMID- 29654285
TI  - Cell-free prediction of protein expression costs for growing cells.
AB  - Translating heterologous proteins places significant burden on host cells,
      consuming expression resources leading to slower cell growth and productivity.
      Yet predicting the cost of protein production for any given gene is a major
      challenge, as multiple processes and factors combine to determine translation
      efficiency. To enable prediction of the cost of gene expression in bacteria, we
      describe here a standard cell-free lysate assay that provides a relative measure
      of resource consumption when a protein coding sequence is expressed. These lysate
      measurements can then be used with a computational model of translation to
      predict the in vivo burden placed on growing E. coli cells for a variety of
      proteins of different functions and lengths. Using this approach, we can predict
      the burden of expressing multigene operons of different designs and differentiate
      between the fraction of burden related to gene expression compared to action of a
      metabolic pathway.

PMID- 29654286
TI  - Automatic gain control of neural coupling during cooperative hand movements.
AB  - Cooperative hand movements (e.g. opening a bottle) are controlled by a task
      specific neural coupling, reflected in EMG reflex responses contralateral to the
      stimulation site. In this study the contralateral reflex responses in forearm
      extensor muscles to ipsilateral ulnar nerve stimulation was analyzed at various
      resistance and velocities of cooperative hand movements. The size of
      contralateral reflex responses was closely related to the level of forearm muscle
      activation required to accomplish the various cooperative hand movement tasks.
      This indicates an automatic gain control of neural coupling that allows a rapid
      matching of corrective forces exerted at both sides of an object with the goal
      'two hands one action'.

PMID- 29654284
TI  - Activation of hypoxia-inducible factor 1 attenuates periapical inflammation and
      bone loss.
AB  - Hypoxia (low oxygen level) is an important feature during infections and affects
      the host defence mechanisms. The host has evolved specific responses to address
      hypoxia, which are strongly dependent on the activation of hypoxia-inducible
      factor 1 (HIF-1). Hypoxia interferes degradation of HIF-1 alpha subunit (HIF
      1alpha), leading to stabilisation of HIF-1alpha, heterodimerization with HIF-1
      beta subunit (HIF-1beta) and subsequent activation of HIF-1 pathway. Apical
      periodontitis (periapical lesion) is a consequence of endodontic infection and
      ultimately results in destruction of tooth-supporting tissue, including alveolar
      bone. Thus far, the role of HIF-1 in periapical lesions has not been
      systematically examined. In the present study, we determined the role of HIF-1 in
      a well-characterised mouse periapical lesion model using two HIF-1alpha
      activating strategies, dimethyloxalylglycine (DMOG) and adenovirus-induced
      constitutively active HIF-1alpha (CA-HIF1A). Both DMOG and CA-HIF1A attenuated
      periapical inflammation and tissue destruction. The attenuation in vivo was
      associated with downregulation of nuclear factor-kappaappa B (NF-kappaB) and
      osteoclastic gene expressions. These two agents also suppressed NF-kappaB
      activation and subsequent production of proinflammatory cytokines by macrophages.
      Furthermore, activation of HIF-1alpha by DMOG specifically suppressed
      lipopolysaccharide-stimulated macrophage differentiation into M1 cells,
      increasing the ratio of M2 macrophages against M1 cells. Taken together, our data
      indicated that activation of HIF-1 plays a protective role in the development of
      apical periodontitis via downregulation of NF-kappaB, proinflammatory cytokines,
      M1 macrophages and osteoclastogenesis.

PMID- 29654287
TI  - Effects of noise on the internal resonance of a nonlinear oscillator.
AB  - We numerically analyze the response to noise of a system formed by two coupled
      mechanical oscillators, one of them having Duffing and van der Pol
      nonlinearities, and being excited by a self-sustaining force proportional to its
      own velocity. This system models the internal resonance of two oscillation modes
      in a vibrating solid beam clamped at both ends. In applications to nano- and
      micromechanical devices, clamped-clamped beams are subjected to relatively large
      thermal and electronic noise, so that characterizing the fluctuations induced by
      these effects is an issue of both scientific and technological interest. We pay
      particular attention to the action of stochastic forces on the stability of
      internal-resonance motion, showing that resonant oscillations become more robust
      than other forms of periodic motion as the quality factor of the resonant mode
      increases. The dependence on other model parameters -in particular, on the
      coupling strength between the two oscillators- is also assessed.

PMID- 29654288
TI  - Cytotect(r)CP as salvage therapy in patients with CMV infection following
      allogeneic hematopoietic cell transplantation: a multicenter retrospective study.
AB  - Cytomegalovirus is one of the main contributing factors to high mortality rates
      in patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT).
      The main factors of treatment failure are both drug resistance and intolerance.
      In some cases, Cytotect(r)CP CMV-hyperimmune globulin is used as salvage therapy.
      This study aims to investigate the safety and efficacy of Cytotect(r)CP as a
      salvage therapy in patients with CMV infection after allo-HCT. Twenty-three
      consecutive patients received Cytotect(r)CP for CMV infection after prior CMV
      therapy. At the time of Cytotect(r)CP introduction, 17 patients (74%) had
      developed acute GVHD and 15 patients (64%) were receiving steroid treatment;
      Cytotect(r)CP was used as monotherapy (n = 7) and in combination (n = 16).
      Overall, response was observed in 18 patients (78%) with a median time of 15 days
      (range: 3-51). Of the 18 responders, 4 experienced CMV reactivation, while 5
      responders died within 100 days of beginning treatment. Of these 5 deaths, 4 were
      due to causes unrelated to CMV. Estimated 100-day OS from the introduction of
      Cytotect(r)CP was 69.6%. No statistically significant difference was observed in
      100-day OS between responders and non-responders (73.7% vs 50.0%, p = 0.258).
      Cytotect(r)CP as salvage therapy is effective and well-tolerated. Given its
      safety profile, early treatment use should be considered.

PMID- 29654289
TI  - Hematopoietic cell transplantation comorbidity index and risk of developing
      invasive fungal infections after allografting.
AB  - We evaluated the potential correlation of the hematopoietic cell transplantation
      comorbidity index (HCT-CI) with the risk of developing post-transplant invasive
      fungal infections (IFIs). Between January 2009 and March 2015, 312 consecutive
      patients who received a first allograft entered the study. Low/intermediate HCT
      CI risk score (0-2) was observed in 172/312 (55%), whereas high HCT-CI score
      (>=3) was seen in 140/312 (45%). Overall, 51/312 (16%) patients experienced IFI,
      defined as possible in 19 (6%), probable in 27 (9%), and proven in 5 (2%).
      Cumulative incidence of probable-proven IFI at 1 year was 8.5% with a significant
      higher incidence in patients with high HCT-CI (12%) vs. those with low
      intermediate HCT-CI (5%; p = 0.006). There was a strong trend for a higher
      incidence of baseline severe pulmonary comorbidity in patients who developed
      probable-proven IFI (p = 0.051). One-year cumulative incidence of non-relapse
      mortality was higher in patients with IFI vs. those without, 49 and 16% (p <
      0.001). By multivariate analysis, disease status at transplant and high HCT-CI,
      when combined with acute GVHD, were independently associated with the risk of
      post-transplant IFI. This study shows that a high HCT-CI predicts the risk of
      developing IFI and may indicate the need of mold-active antifungal prophylaxis in
      high-risk patients.

PMID- 29654290
TI  - Function of alanine racemase in the physiological activity and cariogenicity of
      Streptococcus mutans.
AB  - The enzyme alanine racemase (Alr) has been a new target for the development of
      antibacterial drugs based on the involvement of D-Ala in bacterial cell wall
      biosynthesis. Our previous study noted that Alr is essential for the growth and
      interspecies competitiveness of S. mutans, the major causative organism of dental
      caries. However, physiological activity and cariogenicity of S. mutans affected
      by Alr remains unknown. The current study examined the biofilm biomass, biofilm
      structure, extracellular polysaccharide (EPS) synthesis, glucosyltransferase
      (gtf) gene expression, acid production and acid tolerance in the alr-mutant
      strain. We found that biofilm formation, biofilm structure, and EPS synthesis was
      in a D-Ala dose-dependent manner. Biofilm structure was loose in alr-mutant group
      and the ratio of EPS/bacteria was also elevated. Additionally, the expression
      levels of multiple gtfs were up-regulated, and acid tolerance was decreased. We
      also established in vivo models of dental caries and found that the incidence and
      severity of the caries were decreased in the alr-mutant group in comparison to
      the parental S. mutans group. Our in vivo and in vitro experiments demonstrate
      that Alr is essential for the cariogenicity of S. mutans and that Alr might be a
      potential target for the prevention and treatment of caries.

PMID- 29654291
TI  - Muscle synergies are consistent across level and uphill treadmill running.
AB  - This study aimed to identify muscle synergies of the lower limb during treadmill
      running on level and inclined ground. Eight subjects ran on a treadmill at three
      speeds (2.5, 3.3, and 4.1 m/s) and two grades (level and 10% grade). Surface
      electromyographic (EMG) signals were recorded from 10 muscles of the lower limb,
      including deeper muscles such as vastus intermedius, adductor magnus, and
      adductor longus. Muscle synergies were extracted applying a non-negative matrix
      factorization algorithm, and relative co-activations across muscles and the
      temporal recruitment pattern were identified by muscle synergy vector and synergy
      activation coefficient, respectively. The scalar product between pairs of synergy
      vectors and synergy activation coefficients during level and uphill running
      conditions were analyzed as a similarity index, with values above 0.8 recognized
      as similar. Approximately 4 muscle synergies controlled the majority of
      variability in 10 EMGs during running, and were common between level and uphill
      conditions. At each running speed, inter-condition similarity was observed in
      synergy vector (r > 0.83) and synergy activation coefficients (r > 0.84) at each
      type of synergy. These results suggest that types of synergy are consistent
      between level and uphill running.

PMID- 29654292
TI  - Photoreceptor-induced RPE phagolysosomal maturation defects in Stargardt-like
      Maculopathy (STGD3).
AB  - For many neurodegenerative disorders, expression of a pathological protein by one
      cell type impedes function of other cell types, which in turn contributes to the
      death of the first cell type. In transgenic mice modelling Stargardt-like (STGD3)
      maculopathy, human mutant ELOVL4 expression by photoreceptors is associated with
      defects in the underlying retinal pigment epithelium (RPE). To examine how
      photoreceptors exert cytotoxic effects on RPE cells, transgenic ELOVL4 (TG1-2
      line; TG) and wild-type (WT) littermates were studied one month prior
      (preclinical stage) to onset of photoreceptor loss (two months). TG photoreceptor
      outer segments presented to human RPE cells are recognized and internalized into
      phagosomes, but their digestion is delayed. Live RPE cell imaging pinpoints
      decreased numbers of acidified phagolysomes. In vivo, master regulator of
      lysosomal genes, transcription factor EB (TFEB), and key lysosomal enzyme
      Cathepsin D are both unaffected. Oxidative stress, as ruled out with high
      resolution respirometry, does not play a role at such an early stage.
      Upregulation of CRYBA1/A3 and phagocytic cells (microglia/macrophages) interposed
      between RPE and photoreceptors support adaptive responses to processing delays.
      Impaired phagolysosomal maturation is observed in RPE of mice expressing human
      mutant ELOVL4 in their photoreceptors prior to photoreceptor death and associated
      vision loss.

PMID- 29654293
TI  - How to curb production of chemical weapons.

PMID- 29654294
TI  - hTERT gene knockdown enhances response to radio- and chemotherapy in head and
      neck cancer cell lines through a DNA damage pathway modification.
AB  - The aim of the study was to analyze the effect of hTERT gene knockdown in HNSCC
      cells by using novel in vitro models of head and neck cancer (HNSCC), as well as
      improving its personalized therapy. To obtain the most efficient knockdown siRNA,
      shRNA-bearing lentiviral vectors were used. The efficiency of hTERT silencing was
      verified with qPCR, Western blot, and immunofluorescence staining. Subsequently,
      the type of cell death and DNA repair mechanism induction after hTERT knockdown
      was assessed with the same methods, followed by flow cytometry. The effect of a
      combined treatment with hTERT gene knockdown on Double-Strand Breaks levels was
      also evaluated by flow cytometry. Results showed that the designed siRNAs and
      shRNAs were effective in hTERT knockdown in HNSCC cells. Depending on a cell
      line, hTERT knockdown led to a cell cycle arrest either in phase G1 or phase
      S/G2. Induction of apoptosis after hTERT downregulation with siRNA was observed.
      Additionally, hTERT targeting with lentiviruses, followed by cytostatics
      administration, led to induction of apoptosis. Interestingly, an increase in
      Double-Strand Breaks accompanied by activation of the main DNA repair mechanism,
      NER, was also observed. Altogether, we conclude that hTERT knockdown
      significantly contributes to the efficacy of HNSCC treatment.

PMID- 29654295
TI  - Antihypertensive effect of etamicastat in dopamine D2 receptor-deficient mice.
AB  - Abnormalities of the D2R gene (DRD2) play a role in the pathogenesis of human
      essential hypertension; variants of the DRD2 have been reported to be associated
      with hypertension. Disruption of Drd2 (D2-/-) in mice increases blood pressure.
      The hypertension of D2-/- mice has been related, in part, to increased
      sympathetic activity, renal oxidative stress, and renal endothelin B receptor
      (ETBR) expression. We tested in D2-/- mice the effect of etamicastat, a
      reversible peripheral inhibitor of dopamine-beta-hydroxylase that reduces the
      biosynthesis of norepinephrine from dopamine and decreases sympathetic nerve
      activity. Blood pressure was measured in anesthetized D2-/- mice treated with
      etamicastat by gavage, (10 mg/kg), conscious D2-/- mice, and D2+/+ littermates,
      and mice with the D2R selectively silenced in the kidney, treated with
      etamicastat in the drinking water (10 mg/kg per day). Tissue and urinary
      catecholamines and renal expression of selected G protein-coupled receptors,
      enzymes related to the production of reactive oxygen species, and sodium
      transporters were also measured. Etamicastat decreased blood pressure both in
      anesthetized and conscious D2-/- mice and mice with renal-selective silencing of
      D2R to levels similar or close to those measured in D2+/+ littermates.
      Etamicastat decreased cardiac and renal norepinephrine and increased cardiac and
      urinary dopamine levels in D2-/- mice. It also normalized the increased renal
      protein expressions of ETBR, NADPH oxidase isoenzymes, and urinary 8-isoprostane,
      as well as renal NHE3 and NCC, and increased the renal expression of D1R but not
      D5R in D2-/- mice. In conclusion, etamicastat is effective in normalizing the
      increased blood pressure and some of the abnormal renal biochemical alterations
      of D2-/- mice.

PMID- 29654296
TI  - Burden of high blood pressure as a contributing factor to stroke in the Japanese
      community-based diabetic population.
AB  - Diabetes mellitus is characterized by alterations in blood glucose (BG)
      metabolism, and glycated hemoglobin (HbA1c) has been widely used as a marker of
      the BG concentration. Diabetes often coexists with high blood pressure (BP). High
      BP and hyperglycemia are well-known risk factors of stroke. We examined the
      extent to which the increased risk of stroke in diabetic individuals is
      attributable to BP and BG using prospectively collected data from the Japanese
      general population. During an average 8.3 +/- 2.2 years of follow-up, out 1606
      diabetic individuals aged >=40 years who were free of cardiovascular disease, 119
      participants (7.4%) developed stroke. In multivariable analysis, a significant
      difference in the risk of incident stroke was noted among the BP categories,
      including normotension (BP1), prehypertension (BP2), and hypertension (BP3; P for
      trend = 0.001). By contrast, no difference was noted among the BG categories,
      including HbA1c levels <7.0% (HB1), 7.0-7.9% (HB2), and >=8.0% (HB3; P for trend
      = 0.430). Compared with the category that included both BP1 and HB1, the
      population-attributable fraction (PAF) for stroke incidence was 52.0% from the
      BP2 and BP3 categories and 24.1% from the HB2 and HB3 categories, and the
      increased incidence from the HB2 and HB3 categories was mostly caused from
      coexistent BP2 and BP3 categories. In conclusion, in the Japanese community-based
      diabetic population, concomitant BP elevation largely contributes to the
      increased incidence of stroke and links BG elevation, as indicated by HbA1c, to
      the increased risk of stroke.

PMID- 29654297
TI  - CKD in diabetes: diabetic kidney disease versus nondiabetic kidney disease.
AB  - The increasing global prevalence of type 2 diabetes mellitus (T2DM) and chronic
      kidney disease (CKD) has prompted research efforts to tackle the growing epidemic
      of diabetic kidney disease (DKD; also known as diabetic nephropathy). The limited
      success of much of this research might in part be due to the fact that not all
      patients diagnosed with DKD have renal dysfunction as a consequence of their
      diabetes mellitus. Patients who present with CKD and diabetes mellitus (type 1 or
      type 2) can have true DKD (wherein CKD is a direct consequence of their diabetes
      status), nondiabetic kidney disease (NDKD) coincident with diabetes mellitus, or
      a combination of both DKD and NDKD. Preclinical studies using models that more
      accurately mimic these three entities might improve the ability of animal models
      to predict clinical trial outcomes. Moreover, improved insights into the
      pathomechanisms that are shared by these entities - including sodium-glucose
      cotransporter 2 (SGLT2) and renin-angiotensin system-driven glomerular
      hyperfiltration and tubular hyper-reabsorption - as well as those that are unique
      to individual entities might lead to the identification of new treatment targets.
      Acknowledging that the clinical entity of CKD plus diabetes mellitus encompasses
      NDKD as well as DKD could help solve some of the urgent unmet medical needs of
      patients affected by these conditions.

PMID- 29654298
TI  - Abnormal saline and the history of intravenous fluids.

PMID- 29654299
TI  - Incorporation of bridged nucleic acids into CRISPR RNAs improves Cas9
      endonuclease specificity.
AB  - Off-target DNA cleavage is a paramount concern when applying CRISPR-Cas9 gene
      editing technology to functional genetics and human therapeutic applications.
      Here, we show that incorporation of next-generation bridged nucleic acids (2',4'
      BNANC[N-Me]) as well as locked nucleic acids (LNA) at specific locations in
      CRISPR-RNAs (crRNAs) broadly reduces off-target DNA cleavage by Cas9 in vitro and
      in cells by several orders of magnitude. Using single-molecule FRET experiments
      we show that BNANC incorporation slows Cas9 kinetics and improves specificity by
      inducing a highly dynamic crRNA-DNA duplex for off-target sequences, which
      shortens dwell time in the cleavage-competent, "zipped" conformation. In addition
      to describing a robust technique for improving the precision of CRISPR/Cas9-based
      gene editing, this study illuminates an application of synthetic nucleic acids.

PMID- 29654300
TI  - Fossil black smoker yields oxygen isotopic composition of Neoproterozoic
      seawater.
AB  - The evolution of the seawater oxygen isotopic composition (delta18O) through
      geological time remains controversial. Yet, the past delta18Oseawater is key to
      assess past seawater temperatures, providing insights into past climate change
      and life evolution. Here we provide a new and unprecedentedly precise delta18O
      value of -1.33 +/- 0.980/00 for the Neoproterozoic bottom seawater supporting a
      constant oxygen isotope composition through time. We demonstrate that the Ait
      Ahmane ultramafic unit of the ca. 760 Ma Bou Azzer ophiolite (Morocco) host a
      fossil black smoker-type hydrothermal system. In this system we analyzed an
      untapped archive for the ocean oxygen isotopic composition consisting in pure
      magnetite veins directly precipitated from a Neoproterozoic seawater-derived
      fluid. Our results suggest that, while delta18Oseawater and submarine
      hydrothermal processes were likely similar to present day, Neoproterozoic oceans
      were 15-30  degrees C warmer on the eve of the Sturtian glaciation and the major
      life diversification that followed.

PMID- 29654301
TI  - Accessing valley degree of freedom in bulk Tin(II) sulfide at room temperature.
AB  - The field of valleytronics has promised greater control of electronic and
      spintronic systems with an additional valley degree of freedom. However,
      conventional and two-dimensional valleytronic systems pose practical challenges
      in the utilization of this valley degree of freedom. Here we show experimental
      evidences of the valley effect in a bulk, ambient, and bias-free model system of
      Tin(II) sulfide. We elucidate the direct access and identification of different
      sets of valleys, based primarily on the selectivity in absorption and emission of
      linearly polarized light by optical reflection/transmission and photoluminescence
      measurements, and demonstrate strong optical dichroic anisotropy of up to 600%
      and nominal polarization degrees of up to 96% for the two valleys with band-gap
      values 1.28 and 1.48 eV, respectively; the ease of valley selection further
      manifested in their non-degenerate nature. Such discovery enables a new platform
      for better access and control of valley polarization.

PMID- 29654302
TI  - Orientation-dependent Dxz4 contacts shape the 3D structure of the inactive X
      chromosome.
AB  - The mammalian inactive X chromosome (Xi) condenses into a bipartite structure
      with two superdomains of frequent long-range contacts, separated by a hinge
      region. Using Hi-C in edited mouse cells with allelic deletions or inversions
      within the hinge, here we show that the conserved Dxz4 locus is necessary to
      maintain this bipartite structure. Dxz4 orientation controls the distribution of
      contacts on the Xi, as shown by a massive reversal in long-range contacts after
      Dxz4 inversion. Despite an increase in CTCF binding and chromatin accessibility
      on the Xi in Dxz4-edited cells, only minor changes in TAD structure and gene
      expression were detected, in accordance with multiple epigenetic mechanisms
      ensuring X silencing. We propose that Dxz4 represents a structural platform for
      frequent long-range contacts with multiple loci in a direction dictated by the
      orientation of its bank of CTCF motifs, which may work as a ratchet to form the
      distinctive bipartite structure of the condensed Xi.

PMID- 29654303
TI  - Hedgehog Interacting Protein Promotes Fibrosis and Apoptosis in Glomerular
      Endothelial Cells in Murine Diabetes.
AB  - We investigated whether renal hedgehog interacting protein (Hhip) expression
      contributes to the progression of diabetic nephropathy (DN) and studied its
      related mechanism(s) in vivo and in vitro. Here, we show that Hhip expression is
      highly elevated in glomerular endothelial cells of adult type 1 diabetic (T1D)
      Akita and T2D db/db mouse kidneys as compared to non-diabetic control
      littermates. Hyperglycemia enhances reactive oxygen species (ROS) generation via
      NADPH oxidase 4 (Nox4) activation and stimulates renal Hhip gene expression, and
      that elevated renal Hhip gene expression subsequently activates the TGFbeta1-
      Smad2/3 cascade and promotes endothelial to mesenchymal transition associated
      with endothelial cell fibrosis/apoptosis in vivo and in vitro. Furthermore,
      kidneys of low-dose streptozotocin-induced diabetic heterozygous Hhip deficient
      (Hhip+/-) mice displayed a normal albumin/creatinine ratio with fewer features of
      DN (glomerulosclerosis/fibrosis and podocyte apoptosis/loss) and less evidence of
      renal compensation (glomerular hypertrophy and hyperfiltration) as compared to
      diabetic wild type controls (Hhip+/+). Thus, our studies demonstrated that renal
      Hhip expression is associated with nephropathy development in diabetes and that
      hyperglycemia-induced renal Hhip expression may mediate glomerular endothelial
      fibrosis and apoptosis in diabetes, a novel finding.

PMID- 29654305
TI  - Publisher Correction: Feed gas effect on plasma inactivation mechanism of
      Salmonella Typhimurium in onion and quality assessment of the treated sample.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 29654304
TI  - Defective immuno- and thymoproteasome assembly causes severe immunodeficiency.
AB  - By N-ethyl-N-nitrosourea (ENU) mutagenesis, we generated the mutant mouse line
      TUB6 that is characterised by severe combined immunodeficiency (SCID) and
      systemic sterile autoinflammation in homozygotes, and a selective T cell defect
      in heterozygotes. The causative missense point mutation results in the single
      amino acid exchange G170W in multicatalytic endopeptidase complex subunit-1 (MECL
      1), the beta2i-subunit of the immuno- and thymoproteasome. Yeast mutagenesis and
      crystallographic data suggest that the severe TUB6-phenotype compared to the MECL
      1 knockout mouse is caused by structural changes in the C-terminal appendage of
      beta2i that prevent the biogenesis of immuno- and thymoproteasomes. Proteasomes
      are essential for cell survival, and defective proteasome assembly causes
      selective death of cells expressing the mutant MECL-1, leading to the severe
      immunological phenotype. In contrast to the immunosubunits beta1i (LMP2) and
      beta5i (LMP7), mutations in the gene encoding MECL-1 have not yet been assigned
      to human disorders. The TUB6 mutant mouse line exemplifies the involvement of
      MECL-1 in immunopathogenesis and provides the first mouse model for primary
      immuno- and thymoproteasome-associated immunodeficiency that may also be relevant
      in humans.

PMID- 29654306
TI  - Proinflammatory cytokines and response to molds in mononuclear cells of patients
      with Meniere disease.
AB  - Epidemiological studies have found a higher prevalence of allergic symptoms and
      positive prick tests in patients with Meniere's disease (MD); however the effect
      of allergenic extracts in MD has not been established. Thus, this study aims to
      determine the effect of Aspergillus and Penicillium stimulation in cytokine
      release and gene expression profile in MD. Patients with MD showed higher basal
      levels of IL-1beta, IL-1RA, IL-6 and TNF-alpha when compared to healthy controls.
      We observed that IL-1beta levels had a bimodal distribution suggesting two
      different subgroups of patients, with low and high basal levels of cytokines.
      Gene expression profile in peripheral blood mononuclear cells (PBMC) showed
      significant differences in patients with high and low basal levels of IL-1beta.
      We found that both mold extracts triggered a significant release of TNF-alpha in
      MD patients, which were not found in controls. Moreover, after mold stimulation,
      MD patients showed a different gene expression profile in PBMC, according to the
      basal levels of IL-1beta. The results indicate that a subset of MD patients have
      higher basal levels of proinflammatory cytokines and the exposure to Aspergillus
      and Penicillium extracts may trigger additional TNF-alpha release and contribute
      to exacerbate inflammation.

PMID- 29654307
TI  - Highly extended filaments in aqueous gold nano-particle colloidals.
AB  - A new regime of filamentation has been discovered in aqueous gold nanoparticle
      colloidals (AGNC). Different from filamentation in liquids, in this regime, by
      doping water with gold nanoparticles, there is no observable multiple small-scale
      filaments, but instead a spatially continuous plasma channel is formed. The
      length of the filament is more than ten times as compared with that in water.
      Filamentation in AGNC is characterized by a colorful light channel, with
      generated supercontinuum ranging from 400 nm to 650 nm which is scattered along a
      cyan-orange path.

PMID- 29654308
TI  - Safety of Low-calcium Dialysate and its Effects on Coronary Artery Calcification
      in Patients Undergoing Maintenance Hemodialysis.
AB  - To determine the safety of low-calcium-dialysate in patients undergoing
      maintenance hemodialysis (MHD) and its effects on coronary artery calcification
      (CAC) and analyze clinical risk factors for CAC. A total of 174 MHD patients were
      recruited and randomly divided into two groups: high-calcium dialysate (HCD, 1.5
      mmol/L Ca2+) and low-calcium dialysate (LCD, 1.25 mmol/L Ca2+). Changes in CAC
      score (CACS) and cardiac function were evaluated using spiral computed tomography
      and echocardiography, respectively. Clinical and laboratory parameters were
      measured. Intra-dialysis adverse reactions were recorded and compared between the
      two groups. CACS was significantly lower in the LCD group than in the HCD group
      by the end of the study. Cardiac E/Amax was significantly higher in the LCD group
      than in the HCD group by the end of the study. There was no significant
      difference in the frequency of any intra-dialysis adverse reactions between the
      two groups during the study. LCD is helpful in maintaining cardiac diastolic
      function and postponing CAC progression. LCD does not increase intra-dialysis
      adverse reactions. Age may be the most important factor impacting CAC in MHD
      patients.

PMID- 29654309
TI  - Spatial fishing restrictions benefit demersal stocks in the northeastern
      Mediterranean Sea.
AB  - The multi-level benefits that marine organisms gain when protected from fishing
      are well acknowledged. Here, we investigated the effects of a 40-year trawling
      ban on the status of targeted and non-targeted marine species within a major
      fishing ground in the northeastern Mediterranean Sea (Thermaikos Gulf, Aegean
      Sea). Biomass and somatic length of fish and invertebrates (six commercial and
      three non-commercial demersal species) were measured in three areas of varying
      fishing pressure, depending on the temporal and spatial operational regimes of
      fishing vessels. The positive effects of fishing restrictions on the studied
      demersal stocks were clearly revealed, as the commercial fish species exhibited
      higher biomass in the intermediate and low pressure areas, as well as increasing
      maximum and mean total length (and other length indicators) with decreasing
      fishing effort. The mean total length of non-commercial species generally did not
      differ among areas, except for species caught and discarded at high rates. The
      present study shows that fishing does alter the population structure and biomass
      of commercial demersal species, and that fishing restrictions greatly contribute
      to improving the status of demersal populations within the restricted areas by
      providing a refuge for large individuals and their important contribution to the
      gene pool.

PMID- 29654310
TI  - APOBEC3-mediated restriction of RNA virus replication.
AB  - APOBEC3 family members are cytidine deaminases with roles in intrinsic responses
      to infection by retroviruses and retrotransposons, and in the control of other
      DNA viruses, such as herpesviruses, parvoviruses and hepatitis B virus. Although
      effects of APOBEC3 members on viral DNA have been demonstrated, it is not known
      whether they edit RNA genomes through cytidine deamination. Here, we investigated
      APOBEC3-mediated restriction of Coronaviridae. In experiments in vitro, three
      human APOBEC3 proteins (A3C, A3F and A3H) inhibited HCoV-NL63 infection and
      limited production of progeny virus, but did not cause hypermutation of the
      coronaviral genome. APOBEC3-mediated restriction was partially dependent on
      enzyme activity, and was reduced by the use of enzymatically inactive APOBEC3.
      Moreover, APOBEC3 proteins bound to the coronaviral nucleoprotein, and this
      interaction also affected viral replication. Although the precise molecular
      mechanism of deaminase-dependent inhibition of coronavirus replication remains
      elusive, our results further our understanding of APOBEC-mediated restriction of
      RNA virus infections.

PMID- 29654313
TI  - Publisher Correction: Inflammation induces two types of inflammatory dendritic
      cells in inflamed lymph nodes.
AB  - The original version of this article unfortunately contained an error in the
      author name Dongchan Yang, which was incorrectly given as Dongchan Yang Sung.

PMID- 29654312
TI  - Decoding the influence of anticipatory states on visual perception in the
      presence of temporal distractors.
AB  - Anticipatory states help prioritise relevant perceptual targets over competing
      distractor stimuli and amplify early brain responses to these targets. Here we
      combine electroencephalography recordings in humans with multivariate stimulus
      decoding to address whether anticipation also increases the amount of target
      identity information contained in these responses, and to ask how targets are
      prioritised over distractors when these compete in time. We show that
      anticipatory cues not only boost visual target representations, but also delay
      the interference on these target representations caused by temporally adjacent
      distractor stimuli-possibly marking a protective window reserved for high
      fidelity target processing. Enhanced target decoding and distractor resistance
      are further predicted by the attenuation of posterior 8-14 Hz alpha oscillations.
      These findings thus reveal multiple mechanisms by which anticipatory states help
      prioritise targets from temporally competing distractors, and they highlight the
      potential of non-invasive multivariate electrophysiology to track cognitive
      influences on perception in temporally crowded contexts.

PMID- 29654311
TI  - A TAD boundary is preserved upon deletion of the CTCF-rich Firre locus.
AB  - The binding of the transcriptional regulator CTCF to the genome has been
      implicated in the formation of topologically associated domains (TADs). However,
      the general mechanisms of folding the genome into TADs are not fully understood.
      Here we test the effects of deleting a CTCF-rich locus on TAD boundary formation.
      Using genome-wide chromosome conformation capture (Hi-C), we focus on one TAD
      boundary on chromosome X harboring ~ 15 CTCF binding sites and located at the
      long non-coding RNA (lncRNA) locus Firre. Specifically, this TAD boundary is
      invariant across evolution, tissues, and temporal dynamics of X-chromosome
      inactivation. We demonstrate that neither the deletion of this locus nor the
      ectopic insertion of Firre cDNA or its ectopic expression are sufficient to alter
      TADs in a sex-specific or allele-specific manner. In contrast, Firre's deletion
      disrupts the chromatin super-loop formation of the inactive X-chromosome.
      Collectively, our findings suggest that apart from CTCF binding, additional
      mechanisms may play roles in establishing TAD boundary formation.

PMID- 29654314
TI  - Comparative biogeography of the gut microbiome between Jinhua and Landrace pigs.
AB  - The intestinal microbiome is critically important in shaping a variety of host
      physiological responses. However, it remains elusive on how gut microbiota
      impacts overall growth and more specifically, adipogenesis. Using the pig as an
      animal model, we compared the differences in bacterial community structure
      throughout the intestinal tract in two breeds (Landrace and Jinhua) of pigs with
      distinct phenotypes. The Landrace is a commercial purebred and the Jinhua is a
      Chinese indigenous, slow-growing breed with high propensity for fat deposition.
      Using 16S rRNA gene sequencing, we revealed that the bacterial communities are
      more diverse in the duodenum, jejunum, and cecum of Jinhua pigs than in those of
      Landrace pigs, whereas the ileal and colonic microbiota show a similar complexity
      between the two breeds. Furthermore, a number of bacterial taxa differentially
      exist in Jinhua and Landrace pigs throughout the entire intestinal tract, with
      the jejunal and ileal microbiome showing the greatest contrast. Functional
      prediction of the bacterial community suggested increased fatty acid biosynthesis
      in Jinghua pigs, which could partially explain their adiposity phenotype. Further
      studies are warranted to experimentally verify the relative contribution of each
      enriched bacterial species and their effect on adipogenesis and animal growth.

PMID- 29654315
TI  - Real-time magnetic actuation of DNA nanodevices via modular integration with
      stiff micro-levers.
AB  - DNA nanotechnology has enabled complex nanodevices, but the ability to directly
      manipulate systems with fast response times remains a key challenge. Current
      methods of actuation are relatively slow and only direct devices into one or two
      target configurations. Here we report an approach to control DNA origami
      assemblies via externally applied magnetic fields using a low-cost platform that
      enables actuation into many distinct configurations with sub-second response
      times. The nanodevices in these assemblies are manipulated via mechanically stiff
      micron-scale lever arms, which rigidly couple movement of a micron size magnetic
      bead to reconfiguration of the nanodevice while also enabling direct
      visualization of the conformation. We demonstrate control of three assemblies-a
      rod, rotor, and hinge-at frequencies up to several Hz and the ability to actuate
      into many conformations. This level of spatiotemporal control over DNA devices
      can serve as a foundation for real-time manipulation of molecular and atomic
      systems.

PMID- 29654316
TI  - Immune-cognitive system connectivity reduces bumblebee foraging success in
      complex multisensory floral environments.
AB  - Bumblebees are declining at alarming rate worldwide, posing a significant threat
      to the function and diversity of temperate ecosystems. These declines have been
      attributed, in part, to the direct effect of specific pathogens on bumblebee
      survival. However, pathogens may also have a negative impact on host populations
      indirectly through immune-induced cognitive deficits in infected individuals. To
      gain greater insight into mechanisms and potential conservation implications of
      such 'immune-brain crosstalk' in bumblebees, we non-pathogenetically activated
      humoral and cellular immune pathways in individuals and then tested for long-term
      reductions in cognitive performance and foraging proficiency. We show that
      chronic activation of humoral, but not a cellular, immune pathways and effectors
      in foragers significantly reduces their ability to flexibly and efficiently
      harvest resources in multi-sensory floral environments for at least 7 days post
      treatment. Humoral defense responses thus have the potential to confer
      significant foraging costs to bumblebee foragers over timeframes that would
      negatively impact colony growth and reproductive output under natural conditions.
      Our findings indicate that fitness effects of immune-brain crosstalk should be
      considered before attributing wild bumblebee decline to a particular pathogen
      species.

PMID- 29654317
TI  - On the use of Parylene C polymer as substrate for peripheral nerve electrodes.
AB  - Parylene C is a highly flexible polymer used in several biomedical implants.
      Since previous studies have reported valuable biocompatible and manufacturing
      characteristics for brain and intraneural implants, we tested its suitability as
      a substrate for peripheral nerve electrodes. We evaluated 1-year-aged in vitro
      samples, where no chemical differences were observed and only a slight deviation
      on Young's modulus was found. The foreign body reaction (FBR) to longitudinal
      Parylene C devices implanted in the rat sciatic nerve for 8 months was
      characterized. After 2 weeks, a capsule was formed around the device, which
      continued increasing up to 16 and 32 weeks. Histological analyses revealed two
      cell types implicated in the FBR: macrophages, in contact with the device, and
      fibroblasts, localized in the outermost zone after 8 weeks. Molecular analysis of
      implanted nerves comparing Parylene C and polyimide devices revealed a peak of
      inflammatory cytokines after 1 day of implant, returning to low levels
      thereafter. Only an increase of CCL2 and CCL3 was found at chronic time-points
      for both materials. Although no molecular differences in the FBR to both polymers
      were found, the thick tissue capsule formed around Parylene C puts some concern
      on its use as a scaffold for intraneural electrodes.

PMID- 29654318
TI  - Inhibition of the NLRP3-inflammasome as a potential approach for neuroprotection
      after stroke.
AB  - Activation of the NOD-like receptor protein (NLRP3)-inflammasome has been
      postulated to mediate inflammatory responses to brain damage during
      ischemic/reperfusion (I/R) injury. We therefore hypothesized that MCC950, a
      selective NLRP3-inflammasome inhibitor provides protection in mouse model of
      transient middle cerebral artery occlusion (tMCAO). Focal cerebral ischemia was
      induced by 60 min tMCAO followed by intraperitoneal administration of MCC950 (50
      mg/kg) or saline at 1 h and 3 h post-occlusion. After 24 h of I/R, mice were
      tested for neurological outcome and were sacrificed for the analysis of infarct
      size and estimating NLRP3-inflammasome and apoptotic markers as well.
      Spectrophotometric method was used to determine hemoglobin (Hb) content as a
      marker of intracerebral hemorrhage. MCC950-treated mice showed a substantial
      reduction in infarction, edema and Hb content compared to saline controls in
      parallel with improved neurological deficits. MCC950 reduced expression of NLRP3
      inflammasome cleavage products Caspase-1 and interlukin-1beta (IL-1beta) in
      penumbral region. These protective effects of MCC950 were associated with
      decreased TNF-alpha levels as well as poly (ADP-ribose) polymerase (PARP) and
      Caspase-3 cleavage and paralleled less phosphrylated NFkappaBp65 and IkappaBalpha
      levels. Taken together, these data indicate that inhibition of NLRP3-inflammasome
      with MCC950 has therapeutic potential in ischemic stroke models. Further
      investigations into the therapeutic efficacy and protocols are needed to confirm
      whether MCC950 treatment could be a promising candidate for clinical trials.

PMID- 29654320
TI  - The challenges facing synthetic biology in eukaryotes.

PMID- 29654319
TI  - Rapid increase in atmospheric iodine levels in the North Atlantic since the mid
      20th century.
AB  - Atmospheric iodine causes tropospheric ozone depletion and aerosol formation,
      both of which have significant climate impacts, and is an essential dietary
      element for humans. However, the evolution of atmospheric iodine levels at
      decadal and centennial scales is unknown. Here, we report iodine concentrations
      in the RECAP ice-core (coastal East Greenland) to investigate how atmospheric
      iodine levels in the North Atlantic have evolved over the past 260 years (1750
      2011), this being the longest record of atmospheric iodine in the Northern
      Hemisphere. The levels of iodine tripled from 1950 to 2010. Our results suggest
      that this increase is driven by anthropogenic ozone pollution and enhanced sub
      ice phytoplankton production associated with the recent thinning of Arctic sea
      ice. Increasing atmospheric iodine has accelerated ozone loss and has
      considerably enhanced iodine transport and deposition to the Northern Hemisphere
      continents. Future climate and anthropogenic forcing may continue to amplify
      oceanic iodine emissions with potentially significant health and environmental
      impacts at global scale.

PMID- 29654321
TI  - Publisher Correction: Chimeric peptide EP45 as a dual agonist at GLP-1 and NPY2R
      receptors.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 29654322
TI  - CD4 T cell autophagy is integral to memory maintenance.
AB  - Studies of mice deficient for autophagy in T cells since thymic development,
      concluded that autophagy is integral to mature T cell homeostasis. Basal survival
      and functional impairments in vivo, limited the use of these models to delineate
      the role of autophagy during the immune response. We generated Atg5 f/f distal
      Lck (dLck)-cre mice, with deletion of autophagy only at a mature stage. In this
      model, autophagy deficiency impacts CD8+ T cell survival but has no influence on
      CD4+ T cell number and short-term activation. Moreover, autophagy in T cells is
      dispensable during early humoral response but critical for long-term antibody
      production. Autophagy in CD4+ T cells is required to transfer humoral memory as
      shown by injection of antigen-experienced cells in naive mice. We also observed a
      selection of autophagy-competent cells in the CD4+ T cell memory compartment. We
      performed in vitro differentiation of memory CD4+ T cells, to better characterize
      autophagy-deficient memory cells. We identified mitochondrial and lipid load
      defects in differentiated memory CD4+ T cells, together with a compromised
      survival, without any collapse of energy production. We then propose that memory
      CD4+ T cells rely on autophagy for their survival to regulate toxic effects of
      mitochondrial activity and lipid overload.

PMID- 29654323
TI  - Gold nanocrystal-mediated sliding of doublet DNA origami filaments.
AB  - Sliding is one of the fundamental mechanical movements in machinery. In
      macroscopic systems, double-rack pinion machines employ gears to slide two linear
      tracks along opposite directions. In microscopic systems, kinesin-5 proteins
      crosslink and slide apart antiparallel microtubules, promoting spindle bipolarity
      and elongation during mitosis. Here we demonstrate an artificial nanoscopic
      analog, in which gold nanocrystals can mediate coordinated sliding of two
      antiparallel DNA origami filaments powered by DNA fuels. Stepwise and reversible
      sliding along opposite directions is in situ monitored and confirmed using
      fluorescence spectroscopy. A theoretical model including different energy
      transfer mechanisms is developed to understand the observed fluorescence
      dynamics. We further show that such sliding can also take place in the presence
      of multiple DNA sidelocks that are introduced to inhibit the relative movements.
      Our work enriches the toolbox of DNA-based nanomachinery, taking one step further
      toward the vision of molecular nanofactories.

PMID- 29654324
TI  - Integrated dual-tomography for refractive index analysis of free-floating single
      living cell with isotropic superresolution.
AB  - Digital holographic microtomography is a promising technique for three
      dimensional (3D) measurement of the refractive index (RI) profiles of biological
      specimens. Measurement of the RI distribution of a free-floating single living
      cell with an isotropic superresolution had not previously been accomplished. To
      the best of our knowledge, this is the first study focusing on the development of
      an integrated dual-tomographic (IDT) imaging system for RI measurement of an
      unlabelled free-floating single living cell with an isotropic superresolution by
      combining the spatial frequencies of full-angle specimen rotation with those of
      beam rotation. A novel 'UFO' (unidentified flying object) like shaped coherent
      transfer function is obtained. The IDT imaging system does not require any
      complex image-processing algorithm for 3D reconstruction. The working principle
      was successfully demonstrated and a 3D RI profile of a single living cell,
      Candida rugosa, was obtained with an isotropic superresolution. This technology
      is expected to set a benchmark for free-floating single live sample measurements
      without labeling or any special sample preparations for the experiments.

PMID- 29654325
TI  - Shallow magma diversions during explosive diatreme-forming eruptions.
AB  - The diversion of magma is an important mechanism that may lead to the relocation
      of a volcanic vent. Magma diversion is known to occur during explosive volcanic
      eruptions generating subterranean excavation and remobilization of country and
      volcanic rocks. However, feedbacks between explosive crater formation and
      intrusion processes have not been considered previously, despite their importance
      for understanding evolving hazards during volcanic eruptions. Here, we apply
      numerical modeling to test the impacts of excavation and subsequent infilling of
      diatreme structures on stress states and intrusion geometries during the
      formation of maar-diatreme complexes. Explosive excavation and infilling of
      diatremes affects local stress states which inhibits magma ascent and drives
      lateral diversion at various depths, which are expected to promote intra-diatreme
      explosions, host rock mixing, and vent migration. Our models demonstrate novel
      mechanisms explaining the generation of saucer-shaped sills, linked with magma
      diversion and enhanced intra-diatreme explosive fragmentation during maar
      diatreme volcanism. Similar mechanisms will occur at other volcanic vents
      producing crater-forming eruptions.

PMID- 29654326
TI  - Publisher Correction: Phosphatidylserine-mediated platelet clearance by
      endothelium decreases platelet aggregates and procoagulant activity in sepsis.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 29654327
TI  - Possible superconductivity in the Bismuth IV solid phase under pressure.
AB  - The first successful theory of superconductivity was the one proposed by Bardeen,
      Cooper and Schrieffer in 1957. This breakthrough fostered a remarkable growth of
      the field that propitiated progress and questionings, generating alternative
      theories to explain specific phenomena. For example, it has been argued that
      Bismuth, being a semimetal with a low number of carriers, does not comply with
      the basic hypotheses underlying BCS and therefore a different approach should be
      considered. Nevertheless, in 2016 based on BCS we put forth a prediction that Bi
      at ambient pressure becomes a superconductor at 1.3 mK. A year later an
      experimental group corroborated that in fact Bi is a superconductor with a
      transition temperature of 0.53 mK, a result that eluded previous work. So, since
      Bi is superconductive in almost all the different structures and phases, the
      question is why Bi-IV has been elusive and has not been found yet to
      superconduct? Here we present a study of the electronic and vibrational
      properties of Bi-IV and infer its possible superconductivity using a BCS
      approach. We predict that if the Bi-IV phase structure were cooled down to liquid
      helium temperatures it would also superconduct at a T c of 4.25 K.

PMID- 29654328
TI  - Degradation Kinetics of Inverted Perovskite Solar Cells.
AB  - We explore the degradation behaviour under continuous illumination and direct
      oxygen exposure of inverted unencapsulated
      formamidinium(FA)0.83Cs0.17Pb(I0.8Br0.2)3, CH3NH3PbI3, and CH3NH3PbI3-xClx
      perovskite solar cells. We continuously test the devices in-situ and in-operando
      with current-voltage sweeps, transient photocurrent, and transient photovoltage
      measurements, and find that degradation in the CH3NH3PbI3-xClx solar cells due to
      oxygen exposure occurs over shorter timescales than FA0.83Cs0.17Pb(I0.8Br0.2)3
      mixed-cation devices. We attribute these oxygen-induced losses in the power
      conversion efficiencies to the formation of electron traps within the perovskite
      photoactive layer. Our results highlight that the formamidinium-caesium mixed
      cation perovskites are much less sensitive to oxygen-induced degradation than the
      methylammonium-based perovskite cells, and that further improvements in
      perovskite solar cell stability should focus on the mitigation of trap generation
      during ageing.

PMID- 29654329
TI  - Methane release from the southern Brazilian margin during the last glacial.
AB  - Seafloor methane release can significantly affect the global carbon cycle and
      climate. Appreciable quantities of methane are stored in continental margin
      sediments as shallow gas and hydrate deposits, and changes in pressure,
      temperature and/or bottom-currents can liberate significant amounts of this
      greenhouse gas. Understanding the spatial and temporal dynamics of marine methane
      deposits and their relationships to environmental change are critical for
      assessing past and future carbon cycle and climate change. Here we present
      foraminiferal stable carbon isotope and sediment mineralogy records suggesting
      for the first time that seafloor methane release occurred along the southern
      Brazilian margin during the last glacial period (40-20 cal ka BP). Our results
      show that shallow gas deposits on the southern Brazilian margin responded to
      glacial-interglacial paleoceanographic changes releasing methane due to the
      synergy of sea level lowstand, warmer bottom waters and vigorous bottom currents
      during the last glacial period. High sea level during the Holocene resulted in an
      upslope shift of the Brazil Current, cooling the bottom waters and reducing
      bottom current strength, reducing methane emissions from the southern Brazilian
      margin.

PMID- 29654330
TI  - [Conflicts of interest in guidelines].

PMID- 29654331
TI  - [Injuries of ligaments and tendons of foot and ankle : What every radiologist
      should know].
AB  - Injuries of the ligaments and tendons of the ankle and foot are among the most
      common musculoskeletal injuries. A correct and precise description of the
      pathology and possible accompanying injuries is essential for treatment planning
      by trauma and orthopedic surgeons. While X-ray is used to exclude fractures,
      ultrasound is a very useful tool to assess the ligaments and tendons. For the
      radiologist, magnetic resonance imaging (MRI) is invaluable regarding the correct
      assessment of (partial) ruptures, as well as for evaluating accompanying
      injuries. The aim of the present overview is to provide the most relevant facts
      for radiologists regarding injuries of ligaments and tendons of the ankle and
      foot. A description of expected MRI findings and possible pitfalls are presented.
      For each ligament complex or tendon, we review the anatomy, followed by relevant
      facts on biomechanics and typical findings in case of injury. The lateral and
      medial ligament complex, syndesmosis, spring ligament complex, and the Lisfranc
      ligament are shown in detail. The Achilles tendon and the peroneal tendons are
      also discussed.

PMID- 29654332
TI  - Prevalence and risk factors of psychiatric disorders in early adolescence: 2004
      Pelotas (Brazil) birth cohort.
AB  - PURPOSE: The present study aimed to evaluate the prevalence of psychiatric
      disorders in early adolescence, to examine the distribution of psychiatric
      disorders by maternal and child characteristics and to evaluate the occurrence of
      psychiatric comorbidities. METHODS: This was a prospective cohort study of all
      live births in the city of Pelotas, Brazil, in 2004 (n = 4231). A total of 3562
      subjects were evaluated at 11 years of age. Psychiatric disorders were assessed
      using the Development and Well-Being Assessment. Crude and adjusted logistic
      regression was used to investigate risk factors for any psychiatric disorder.
      RESULTS: According to DSM-5 criteria, the overall prevalence of psychiatric
      disorders was 13.2% (n = 471), 15.6% among the boys and 10.7% among the girls.
      The most common disorders were anxiety disorders (4.3%), any attention
      deficit/hyperactivity disorder (4.0%) and any conduct/oppositional disorder
      (2.8%). Low maternal education, smoking during pregnancy, the presence of moods
      symptoms during pregnancy or maternal chronic and severe depressive symptoms in
      the first years of the adolescent's life, male gender, 5-min Apgar score < 7 at
      birth and preterm birth were associated with higher odds of any psychiatric
      disorder at age 11. Psychiatric comorbidities were observed in 107 subjects
      (22.7%), of whom 73, 24, and 10 had two, three, and four psychiatric diagnoses,
      respectively. CONCLUSIONS: Our results underscore the importance of psychiatric
      disorders as a prevalent condition in early adolescence, which has a direct
      impact on the planning of public policies and specific mental health care
      services in this age group.

PMID- 29654333
TI  - Level 3 guideline on the treatment of patients with severe/multiple injuries :
      AWMF Register-Nr. 012/019.

PMID- 29654334
TI  - Brain morphological and microstructural features in cryptogenic late-onset
      temporal lobe epilepsy: a structural and diffusion MRI study.
AB  - PURPOSE: Although epilepsy in the elderly has attracted attention recently, there
      are few systematic studies of neuroimaging in such patients. In this study, we
      used structural MRI and diffusion tensor imaging (DTI) to investigate the
      morphological and microstructural features of the brain in late-onset temporal
      lobe epilepsy (TLE). METHODS: We recruited patients with TLE and an age of onset
      > 50 years (late-TLE group) and age- and sex-matched healthy volunteers (control
      group). 3-Tesla MRI scans, including 3D T1-weighted images and 15-direction DTI,
      showed normal findings on visual assessment in both groups. We used Statistical
      Parametric Mapping 12 (SPM12) for gray and white matter structural normalization
      and comparison and used Tract-Based Spatial Statistics (TBSS) for fractional
      anisotropy and mean diffusivity comparisons of DTI. In both methods, p < 0.05
      (family-wise error) was considered statistically significant. RESULTS: In total,
      30 patients with late-onset TLE (mean +/- SD age, 66.8 +/- 8.4; mean +/- SD age
      of onset, 63.0 +/- 7.6 years) and 40 healthy controls (mean +/- SD age, 66.6 +/-
      8.5 years) were enrolled. The late-onset TLE group showed significant gray matter
      volume increases in the bilateral amygdala and anterior hippocampus and
      significantly reduced mean diffusivity in the left temporofrontal lobe, internal
      capsule, and brainstem. No significant changes were evident in white matter
      volume or fractional anisotropy. CONCLUSIONS: Our findings may reflect some
      characteristics or mechanisms of cryptogenic TLE in the elderly, such as
      inflammatory processes.

PMID- 29654336
TI  - Highlight report: Mycotoxins as food contaminants in Africa-challenges and
      perspectives.

PMID- 29654335
TI  - Why is the gender gap in life expectancy decreasing? The impact of age- and cause
      specific mortality in Sweden 1997-2014.
AB  - OBJECTIVES: To enhance the understanding of the current increase in life
      expectancy and decreasing gender gap in life expectancy. METHODS: We obtained
      data on underlying cause of death from the National Board of Health and Welfare
      in Sweden for 1997 and 2014 and used Arriaga's method to decompose life
      expectancy by age group and 24 causes of death. RESULTS: Decreased mortality from
      ischemic heart disease had the largest impact on the increased life expectancy of
      both men and women and on the decreased gender gap in life expectancy. Increased
      mortality from Alzheimer's disease negatively influenced overall life expectancy,
      but because of higher female mortality, it also served to decrease the gender gap
      in life expectancy. The impact of other causes of death, particularly smoking
      related causes, decreased in men but increased in women, also reducing the gap in
      life expectancy. CONCLUSIONS: This study shows that a focus on overall changes in
      life expectancies may hide important differences in age- and cause-specific
      mortality. It also emphasizes the importance of addressing modifiable lifestyle
      factors to reduce avoidable mortality.

PMID- 29654337
TI  - Rapid recognition of volatile organic compounds with colorimetric sensor arrays
      for lung cancer screening.
AB  - Volatile organic compounds (VOCs) in breath can be used as biomarkers to identify
      early stages of lung cancer. Herein, we report a disposable colorimetric array
      that has been constructed from diverse chemo-responsive colorants.
      Distinguishable difference maps were plotted within 4 min for specifically
      targeted VOCs. Through the consideration of various chemical interactions with
      VOCs, the arrays successfully discriminate between 20 different volatile organic
      compounds in breath that are related to lung cancer. VOCs were identified either
      with the visualized difference maps or through pattern recognition with an
      accuracy of at least 90%. No uncertainties or errors were observed in the
      hierarchical cluster analysis (HCA). Finally, good reproducibility and stability
      of the array was achieved against changes in humidity. Generally, this work
      provides fundamental support for construction of simple and rapid VOC sensors.
      More importantly, this approach provides a hypothesis-free array method for
      breath testing via VOC profiling. Therefore, this small, rapid, non-invasive,
      inexpensive, and visualized sensor array is a powerful and promising tool for
      early screening of lung cancer. Graphical abstract A disposable colorimetric
      array has been developed with broadly chemo-responsive dyes to incorporate
      various chemical interactions, through which the arrays successfully discriminate
      20 VOCs that are related to lung cancer via difference maps alone or chemometrics
      within 4 min. The hydrophobic porous matrix provides good stability against
      changes in humidity.

PMID- 29654338
TI  - Comprehensive assessment of measurement uncertainty in 13C-based metabolic flux
      experiments.
AB  - In the field of metabolic engineering 13C-based metabolic flux analysis
      experiments have proven successful in indicating points of action. As every step
      of this approach is affected by an inherent error, the aim of the present work is
      the comprehensive evaluation of factors contributing to the uncertainty of
      nonnaturally distributed C-isotopologue abundances as well as to the absolute
      flux value calculation. For this purpose, a previously published data set,
      analyzed in the course of a 13C labeling experiment studying glycolysis and the
      pentose phosphate pathway in a yeast cell factory, was used. Here, for
      isotopologue pattern analysis of these highly polar metabolites that occur in
      multiple isomeric forms, a gas chromatographic separation approach with preceding
      derivatization was used. This rendered a natural isotope interference correction
      step essential. Uncertainty estimation of the resulting C-isotopologue
      distribution was performed according to the EURACHEM guidelines with Monte Carlo
      simulation. It revealed a significant increase for low-abundance isotopologue
      fractions after application of the necessary correction step. For absolute flux
      value estimation, isotopologue fractions of various sugar phosphates, together
      with the assessed uncertainties, were used in a metabolic model describing the
      upper part of the central carbon metabolism. The findings pinpointed the
      influence of small isotopologue fractions as sources of error and highlight the
      need for improved model curation. Graphical abstract ?.

PMID- 29654339
TI  - A novel sandwich enzyme-linked immunosorbent assay with covalently bound
      monoclonal antibody and gold probe for sensitive and rapid detection of bovine
      beta-lactoglobulin.
AB  - Bovine milk is a recognized allergenic food source with beta-lactoglobulin (BLG)
      as its major allergen. Reliable detection of BLG epitopes can, therefore, be a
      useful marker for the presence of milk in processed food products, and for
      potential allergenicity. At the present, enzyme-linked immunosorbent assays
      (ELISA) for the detection of BLG are time-consuming and generally not specific to
      BLG IgE epitopes. In this study, the 1-ethyl-3-(3
      dimethylaminopropyl)carbodiimide-activated anti-BLG IgE epitope monoclonal
      antibody (mAb 1G9) was covalently bound onto the KOH-treated microtiter plate
      surface. Using this mAb-bound plate in sandwich combination with biotinylated
      anti-BLG polyclonal antibody-labeled gold nanoparticles, a linear dynamic range
      between 31.25 and 64 * 103 ng mL-1 with a limit of detection for BLG of 0.49 ng
      mL-1 was obtained, which is 32 times wider and 16 times more sensitive than
      conventional sandwich ELISA (sELISA). Total recovery of BLG in spiked food
      samples was found, without matrix effects. Also in partially hydrolyzed infant
      formulas, the allergenic BLG residues were detected quantitatively. Compared with
      conventional and commercial BLG detection sELISAs, our sELISA is reliable, highly
      BLG epitope-specific, user-friendly, and time-saving and allows accurate
      detection of potentially allergenic residues in different types of processed
      foods. This improved sELISA protocol can be easily extended to detect other well
      identified and characterized food allergens. Graphical abstract IgE epitope mAb
      bound plate in sandwich combination with gold probe for sensitive and rapid
      detection of bovine beta-lactoglobulin and its potentially allergenic residues.

PMID- 29654340
TI  - Degradation product characterization of therapeutic oligonucleotides using liquid
      chromatography mass spectrometry.
AB  - Synthetic antisense phosphorothioate oligonucleotides (PS) have undergone rapid
      development as novel therapeutic agents. The increasing significance of this
      class of drugs requires significant investment in the development of quality
      control methods. The determination of the many degradation pathways of such
      complex molecules presents a significant challenge. However, an understanding of
      the potential impurities that may arise is necessary to continue to advance these
      powerful new therapeutics. In this study, four different antisense
      oligonucleotides representing several generations of oligonucleotide therapeutic
      agents were evaluated under various stress conditions (pH, thermal, and oxidative
      stress) using ion-pairing reversed-phase liquid chromatography tandem mass
      spectrometry (IP-RPLC-MS/MS) to provide in-depth characterization and
      identification of the degradation products. The oligonucleotide samples were
      stressed under different pH values at 45 and 90  degrees C. The main degradation
      products were observed to be losses of nucleotide moieties from the 3'- and 5'
      terminus, depurination, formation of terminal phosphorothioates, and production
      of ribose, ribophosphorothioates (Rp), and phosphoribophosphorothioates (pRp).
      Moreover, the effects of different concentrations of hydrogen peroxide were
      studied resulting in primarily extensive desulfurization and subsequent oxidation
      of the phosphorothioate linkage to produce the corresponding phosphodiester. The
      reaction kinetics for the degradation of the oligonucleotides under the different
      stress conditions were studied and were found to follow pseudo-first-order
      kinetics. Differences in rates exist even for oligonucleotides of similar length
      but consisting of different sequences. Graphical abstract Identification of
      degradation products across several generations of oligonucleotide therapeutics
      using LC-MS.

PMID- 29654341
TI  - Biomimetic trapping cocktail to screen reactive metabolites: use of an amino acid
      and DNA motif mixture as light/heavy isotope pairs differing in mass shift.
AB  - Candidate drugs that can be metabolically transformed into reactive electrophilic
      products, such as epoxides, quinones, and nitroso compounds, are of special
      concern because subsequent covalent binding to bio-macromolecules can cause
      adverse drug reactions, such as allergic reactions, hepatotoxicity, and
      genotoxicity. Several strategies have been reported for screening reactive
      metabolites, such as a covalent binding assay with radioisotope-labeled drugs and
      a trapping method followed by LC-MS/MS analyses. Of these, a trapping method
      using glutathione is the most common, especially at the early stage of drug
      development. However, the cysteine of glutathione is not the only nucleophilic
      site in vivo; lysine, histidine, arginine, and DNA bases are also nucleophilic.
      Indeed, the glutathione trapping method tends to overlook several types of
      reactive metabolites, such as aldehydes, acylglucuronides, and nitroso compounds.
      Here, we introduce an alternate way for screening reactive metabolites as
      follows: A mixture of the light and heavy isotopes of simplified amino acid
      motifs and a DNA motif is used as a biomimetic trapping cocktail. This mixture
      consists of [2H0]/[2H3]-1-methylguanidine (arginine motif, Delta 3 Da),
      [2H0]/[2H4]-2-mercaptoethanol (cysteine motif, Delta 4 Da), [2H0]/[2H5]-4
      methylimidazole (histidine motif, Delta 5 Da), [2H0]/[2H9]-n-butylamine (lysine
      motif, Delta 9 Da), and [13C0,15N0]/[13C1,15N2]-2'-deoxyguanosine (DNA motif,
      Delta 3 Da). Mass tag triggered data-dependent acquisition is used to find the
      characteristic doublet peaks, followed by specific identification of the light
      isotope peak using MS/MS. Forty-two model drugs were examined using an in vitro
      microsome experiment to validate the strategy. Graphical abstract Biomimetic
      trapping cocktail to screen reactive metabolites.

PMID- 29654343
TI  - Osteoimmunology.

PMID- 29654342
TI  - Bisphosphonates for the preservation of periprosthetic bone mineral density after
      total joint arthroplasty: a meta-analysis of 25 randomized controlled trials.
AB  - : The present meta-analysis aimed to evaluate the long-term efficacy of
      bisphosphonates (BPs) on preservation of periprosthetic bone mineral density
      (BMD) after joint arthroplasty. It confirmed the protective effect of BPs in a
      long-term follow-up, and found the influence factors on this effect.
      INTRODUCTION: Periprosthetic bone loss is believed to cause aseptic loosening and
      failed prosthetic fixation in joint arthroplasty. This meta-analysis which
      included high-quality randomized controlled trials aimed to analyze the effect of
      bisphosphonates on maintaining periprosthetic bone mineral density after total
      joint arthroplasty. METHODS: Twenty-five RCTs were included and the total number
      of participants was 1163 by computerized searches of bibliographic databases. The
      weighted mean differences with 95% confidence interval were calculated to
      evaluate the efficacy of BPs on total periprosthetic BMD and the BMD of different
      Gruen zones. Subgroup analyses identified the potentially influencing factors
      such as surgical site, cement fixation, and generation of BPs. A descriptive
      review was conducted for BP-related adverse effects. RESULTS: The BPs group
      presented significantly higher total periprosthetic BMD in the BPs group than
      that in the control group at 3, 6, 12 months, 2-4 years, and 5-10 years after
      arthroplasty (P < 0.05). The BPs group presented significantly higher
      periprosthetic BMD in femoral Gruen Zone 1 and 7 than that in the control group
      at 3, 6, 12 months, 2-4 years, and 5-10 years (P < 0.05). The heterogeneity was
      minimized by dividing THA and TKA into two subgroups. Subgroup analyses revealed
      that the effect of BPs on preservation of BMD was significantly greater in
      arthroplasty with cemented component than in that with uncemented component at 12
      months and 5-10 years (P < 0.05), and the administration of the second and third
      generation BPs was significantly more effective than the first-generation BPs at
      6 and 12 months (P < 0.05). None of the included studies described severe or
      fatal adverse effects related to BPs. CONCLUSIONS: BPs have significantly long
      term efficacy on the preservation of periprosthetic BMD after joint arthroplasty.
      To obtain a better efficacy, the cemented components and the second and third
      generation BPs are recommended.

PMID- 29654344
TI  - Reply: Should we assess repeatability of PET quantitative uptake measurements of
      each 18F-labelled tracer?

PMID- 29654345
TI  - Methylene Blue: A Color Test for a Quality De-epithelialization.

PMID- 29654347
TI  - Is very short-course antibiotic therapy possible in postoperative intra-abdominal
      infections? Discussion on "Short-course antibiotic therapy for critically ill
      patients treated for postoperative intra-abdominal infection: the DURAPOP
      randomised clinical trial".

PMID- 29654348
TI  - Dynamic contrast-enhanced magnetic resonance imaging for differentiating
      osteomyelitis from acute neuropathic arthropathy in the complicated diabetic
      foot.
AB  - OBJECTIVE: The main purpose of this study was to investigate the diagnostic value
      of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating osteomyelitis from
      acute neuropathic arthropathy in the diabetic foot. MATERIALS AND METHODS: This
      prospective study was carried out on 30 diabetic foot patients, with a mean age
      of 51 years. The patients all underwent clinical examinations, laboratory
      examinations and DCE-MRI. The DCE-MRI parameters (Ktrans, Kep and Ve) of the
      regions of acute neuropathic arthropathy and osteomyelitis were calculated.
      Receiver operating characteristic curves (ROCs) were used to identify the DCE-MRI
      parameters that showed the highest accuracy in differentiating the acute
      neuropathic arthropathy from the osteomyelitic regions. Pearson correlation
      coefficients were used to assess the correlations among the DCE-MRI parameters,
      the level of C-reactive protein (CRP) and the erythrocyte sedimentation rate
      (ESR). RESULTS: The Ktrans, Kep and Ve values of the osteomyelitic regions were
      higher than those of the acute neuropathic arthropathy regions, and significant
      differences were found between the two groups (P = 0.000, P = 0.000, P = 0.000).
      The ROC analysis showed that Ktrans and Ve performed best in differentiating
      osteomyelitis from acute neuropathic arthropathy, both with an area under the
      curve of 0.938. The Pearson correlation coefficients showed that the DCE-MRI
      parameters correlated significantly with the level of CRP and ESR (P = 0.000, P =
      0.014, P = 0.000; P = 0.000, P = 0.000, P = 0.013). CONCLUSIONS: Our results
      showed that DCE-MRI may provide reproducible parameters that can reliably
      differentiate osteomyelitis from acute neuropathic arthropathy.

PMID- 29654349
TI  - Prevalence of urinary incontinence in female athletes: a systematic review with
      meta-analysis.
AB  - Urinary incontinence (UI) is any involuntary loss of urine. In female athletes,
      physical exercise may be a risk factor for UI because of increased intra
      abdominal pressure generated during high-impact exercises, which overloads the
      pelvic organs, predisposing them to UI. This is a systematic review of the
      prevalence of UI in female athletes in different sports. A search for articles
      was carried out in the PEDro, Scopus, Cinahl, PubMed, LILACS, SciELO, Science
      Direct, Web of Science, Embase, and Cochrane databases as well as a manual search
      of the references of studies already published on the subject with the keywords
      "athlete," "urinary incontinence," and "women" in Portuguese and English. Only
      articles published from 2000 to 2016 were included. Observational studies
      assessing the prevalence of UI in female athletes were selected. Methodological
      quality was assessed using the Downs and Black scale, and the data collected from
      the studies were analyzed through meta-analysis. Eight studies met the
      eligibility criteria. Meta-analysis showed a 36% prevalence of UI in female
      athletes in different sports, and compared with sedentary women, the athletes had
      a 177% higher risk of presenting with UI. There is a higher prevalence of UI in
      female athletes compared with sedentary women. There have been reports of UI in
      different sports.

PMID- 29654350
TI  - Prospective comparison of obstetric anal sphincter injury incidence between an
      Asian and Western hospital.
AB  - INTRODUCTION AND HYPOTHESIS: Obstetric anal sphincter injury (OASIS) rates are
      reported to be higher in Asian women living in Western countries than in those
      living in Asia, but the reasons for the differences remain unclear. The
      objectives of this study were for a single examiner to prospectively compare
      OASIS rates in primiparous Asian women in an Asian and Western birth unit and
      determine potential birth factors that may influence the possible difference in
      OASIS incidence. METHODS: This was a prospective observational study based in
      Hong Kong, China, and Sydney, Australia, involving primiparous women > 36 weeks
      gestation of Asian descent undergoing vaginal delivery. A single examiner
      recorded basic patient demographics, observed all the deliveries at both sites,
      noting birthing techniques, and then examined the women, including a rectal
      examination, to determine OASIS incidence. RESULTS: Seventy births in Hong Kong
      and 66 in Sydney were studied. The incidence of OASIS was 34% in Sydney and 10%
      in Hong Kong (p = 0.001). Birthweight, epidural rate, body mass index, and
      instrumental delivery were higher in Sydney. Episiotomy rates were higher in Hong
      Kong (59.2% vs. 82.9%; p = 0.007). When comparing OASIS with no-OASIS, perineal
      length (OR = 0.36, 95% CI 0.17 to 0.76, p = 0.004) and birthweight (OR = 1.14,
      95% CI 1.00 to 1.30, p = 0.039) were independent risk factors for OASIS.
      CONCLUSIONS: The incidence of OASIS in Asian women is significantly higher in a
      Western than in an Asian setting. In Asian women, perineal length and birthweight
      can affect the risk of OASIS at the time of vaginal delivery.

PMID- 29654346
TI  - Targeting the intracellular signaling "STOP" and "GO" pathways for the treatment
      of alcohol use disorders.
AB  - In recent years, research has identified the molecular and neural substrates
      underlying the transition of moderate "social" consumption of alcohol to the
      characteristic alcohol use disorder (AUD) phenotypes including excessive and
      compulsive alcohol use which we define in the review as the GO signaling
      pathways. In addition, growing evidence points to the existence of molecular
      mechanisms that keep alcohol consumption in check and that confer resilience for
      the development of AUD which we define herein as the STOP signaling pathways. In
      this review, we focus on examples of the GO and the STOP intracellular signaling
      pathways and discuss our current knowledge of how manipulations of these pathways
      may be used for the treatment of AUD.

PMID- 29654351
TI  - Inhibitory effects of eugenol on putative nociceptive response in spinal cord
      preparation isolated from neonatal rats.
AB  - Eugenol is contained in several plants including clove and is thought to exert an
      analgesic effect. It has been suggested that the slow ventral root potential
      induced by ipsilateral dorsal root stimulation in the isolated (typically lumbar)
      spinal cord of newborn rats reflects the nociceptive response, and this in vitro
      experimental model is useful to assess the actions of analgesics. To further
      elucidate neuronal mechanisms of eugenol-induced analgesia, we examined the
      effects of extracellularly applied eugenol on the nociceptive spinal reflex
      response. To evaluate the effects of eugenol on putative nociceptive responses,
      the ipsilateral fifth lumbar (L5) dorsal root was stimulated using a glass
      suction electrode, and the induced reflex responses were recorded from the L5 and
      twelfth thoracic (Th12) ventral roots in spinal cord preparations (Th10-L5) from
      newborn rats (postnatal day 0-3). We found that eugenol (0.25-1.0 mM) caused dose
      dependent attenuation of the reflex response and also depressed spontaneous
      ventral root activity. We also found that the slow ventral root potential was
      further divided into two components: initial and late components. A lower
      concentration of eugenol selectively depressed the late component. The inhibitory
      effects by 1.0 mM eugenol were not reversed by 10 uM capsazepine (TRPV1
      antagonist) or 40 uM HC-030031 (TRPA1 antagonist). The depressive effect of
      eugenol on the reflex response was also confirmed by optical recordings using
      voltage-sensitive dye. Our report provides additional evidence on the basic
      neuronal mechanisms of eugenol to support its clinical use as a potential
      analgesic treatment.

PMID- 29654353
TI  - DNA methylcytosine dioxygenase ten-eleven translocation 2 enhances
      lipopolysaccharide-induced cytokine expression in human dental pulp cells by
      regulating MyD88 hydroxymethylation.
AB  - Dental pulp inflammation is a bacterially driven inflammation process
      characterized by the local accumulation of cytokines/chemokines that participate
      in destructive processes in the pulp. Multiple mechanisms are involved in dental
      pulp inflammation, including epigenetic events, such as DNA
      methylation/demethylation. Ten-eleven translocation 2 (TET2) is a recently
      discovered DNA methylcytosine dioxygenase that plays important roles in
      inflammatory disease. However, its role in the inflammatory response of dental
      pulp is unknown. We observed elevated mRNA and protein levels of TET2 after
      lipopolysaccharide (LPS) stimulation in human dental pulp cells (hDPCs). To
      identify the effects of TET2 on cytokine expression, TET2 was knocked down and
      cytokines were detected using a cytokine antibody array after LPS stimulation.
      The protein expression of GM-CSF, IL-6, IL-8 and RANTES decreased in the LPS
      induced hDPCs following TET2 knockdown. The downregulated expression levels of IL
      6 and IL-8 were further confirmed by real-time quantitative polymerase chain
      reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). Additionally,
      the phosphorylation levels of IKK-alpha/beta, p65 and IkappaBalpha of the NF
      kappaB signaling pathway were decreased in the TET2-silenced group. Furthermore,
      the global 5-hydroxymethylcytosine (5hmC) level was significantly decreased and
      the genomic 5-methylcytosine (5mC) level was increased in the TET2-deficient
      hDPCs; TET2 depletion resulted in a decrease in the 5hmC level of the MyD88
      promoter following LPS stimulation. These findings indicate that TET2 knockdown
      inhibits LPS-induced inflammatory response in hDPCs by downregulating MyD88
      hydroxymethylation. Thus, TET2-dependent DNA demethylation might play an
      important role in dental pulp inflammation as an epigenetic regulator.

PMID- 29654352
TI  - Occult head injury is common in children with concern for physical abuse.
AB  - BACKGROUND: Studies evaluating small patient cohorts have found a high, but
      variable, rate of occult head injury in children <2 years old with concern for
      physical abuse. The American College of Radiology (ACR) recommends clinicians
      have a low threshold to obtain neuroimaging in these patients. OBJECTIVES: Our
      aim was to determine the prevalence of occult head injury in a large patient
      cohort with suspected physical abuse using similar selection criteria from
      previous studies. Additionally, we evaluated proposed risk factors for
      associations with occult head injury. MATERIALS AND METHODS: This was a
      retrospective, secondary analysis of data collected by an observational study of
      20 U.S. child abuse teams that evaluated children who underwent subspecialty
      evaluation for concern of abuse. We evaluated children <2 years old and excluded
      those with abnormal mental status, bulging fontanelle, seizure, respiratory
      arrest, underlying neurological condition, focal neurological deficit or scalp
      injury. RESULTS: One thousand one hundred forty-three subjects met inclusion
      criteria and 62.5% (714) underwent neuroimaging with either head computed
      tomography or magnetic resonance imaging. We found an occult head injury
      prevalence of 19.7% (141). Subjects with emesis (odds ratio [OR] 3.5, 95%
      confidence interval [CI] 1.8-6.8), macrocephaly (OR 8.5, 95% CI 3.7-20.2), and
      loss of consciousness (OR 5.1, 95% CI 1.2-22.9) had higher odds of occult head
      injury. CONCLUSION: Our results show a high prevalence of occult head injury in
      patients <2 years old with suspected physical abuse. Our data support the ACR
      recommendation that clinicians should have a low threshold to perform
      neuroimaging in patients <2 years of age.

PMID- 29654354
TI  - Application and measurement properties of EQ-5D to measure quality of life in
      patients with upper extremity orthopaedic disorders: a systematic literature
      review.
AB  - INTRODUCTION: The EuroQol-5 Dimension (EQ-5D) is the most widely used generic
      instrument to measure quality of life (QoL), yet its application in upper
      extremity orthopaedics as well as its measurement properties remain largely
      undefined. We implemented a systematic literature review to provide an overview
      of the application of EQ-5D in patients with upper extremity disorders and
      analyse its measurement properties. MATERIALS AND METHODS: We searched Medline,
      EMBASE, Cochrane and Scopus databases for clinical studies including orthopaedic
      patients with surgical interventions of the upper extremity who completed the EQ
      5D. For all included studies, the use of EQ-5D and quantitative QoL data were
      described. Validation studies of EQ-5D were assessed according to COSMIN
      guidelines and standard measurement properties were examined. RESULTS: Twenty
      three studies were included in the review, 19 of which investigated patients with
      an intervention carried out at the shoulder region. In 15 studies, EQ-5D assessed
      QoL as the primary outcome. Utility index scores in non-trauma patients generally
      improved postoperatively, whereas trauma patients did not regain their recalled
      pre-injury QoL levels. EQ-5D measurement properties were reported in three
      articles on proximal humerus fractures and carpal tunnel syndrome. Positive
      ratings were seen for construct validity (Spearman correlation coefficient >=
      0.70 with the Short Form (SF)-12 or SF-6D health surveys) and reliability
      (intraclass correlation coefficient >= 0.77) with intermediate responsiveness
      (standardised response means: 0.5-0.9). However, ceiling effects were identified
      with 16-48% of the patients scoring the maximum QoL. The methodological quality
      of the three articles varied from fair to good. CONCLUSIONS: For surgical
      interventions of the upper extremity, EQ-5D was mostly applied to assess QoL as a
      primary outcome in patients with shoulder disorders. Investigations of the
      measurement properties were rare, but indicate good reliability and validity as
      well as moderate responsiveness in patients with upper extremity conditions.

PMID- 29654355
TI  - Comparison of the paralogous transcription factors AraR and XlnR in Aspergillus
      oryzae.
AB  - The paralogous transcription factors AraR and XlnR in Aspergillus regulate genes
      that are involved in degradation of cellulose and hemicellulose and catabolism of
      pentose. AraR and XlnR target the same genes for pentose catabolism but target
      different genes encoding enzymes for polysaccharide degradation. To uncover the
      relationship between these paralogous transcription factors, we examined their
      contribution to regulation of the PCP genes and compared their preferred
      recognition sequences. Both AraR and XlnR are involved in induction of all the
      pentose catabolic genes in A. oryzae except larA encoding L-arabinose reductase,
      which was regulated by AraR but not by XlnR. DNA-binding studies revealed that
      the recognition sequences of AraR and XlnR also differ only slightly; AraR
      prefers CGGDTAAW, while XlnR prefers CGGNTAAW. All the pentose catabolic genes
      possess at least one recognition site to which both AraR and XlnR can bind.
      Cooperative binding by the factors was not observed. Instead, they competed to
      bind to the shared sites. XlnR bound to the recognition sites mentioned above as
      a monomer, but bound to the sequence TTAGSCTAA on the xylanase promoters as a
      dimer. Consequently, AraR and XlnR have significantly similar, but not the same,
      DNA-binding properties. Such a slight difference in these paralogous
      transcription factors may lead to complex outputs in enzyme production depending
      on the concentrations of coexisting inducer molecules in the natural environment.

PMID- 29654356
TI  - Immobilization of cellulase on thermo-sensitive magnetic microspheres: improved
      stability and reproducibility.
AB  - Magnetic double-shell hybrid microspheres (Fe3O4@SiO2@p(NIPAM-co-GMA)) have been
      developed as a promising supported substrate for the immobilization of cellulase.
      Since the surface of the magnetic microspheres not only contains an epoxy group
      from GMA (glycidyl methacrylate) that can covalently bind to the enzyme, but also
      has an intelligent temperature response property from NIPAM (N
      isopropylacrylamide), the cellulase can be covalently bonded to the magnetic
      microspheres and have a temperature-sensitive capability. The immobilized
      cellulase has the recovery ability of cellulase activity after a high-temperature
      inactivation. The average amount and activity of immobilized enzymes,
      respectively, was 233 mg g-1, 57.4 U mg-1 under the optimized conditions. The
      experimental results show that the immobilized cellulase has a wider catalytic
      temperature range, better temperature and storage stability. The residual
      activity still remained about 65.6% of the initial activity after the sixth
      catalysis run, which indicated that the immobilized enzyme had high
      reproducibility.

PMID- 29654357
TI  - Pretreatment of different food rest materials for bioconversion into fungal lipid
      rich biomass.
AB  - Food rest materials have the potential to be used as media components in various
      types of fermentations. Oleaginous filamentous fungi can utilize those components
      and generate a high-value lipid-rich biomass, which could be further used for
      animal and human use. One of the main limitations in this process is the
      pretreatment of food rest materials, needed to provide homogenization,
      sterilization and solubilization. In this study, two pretreatment processes-steam
      explosion and enzymatic hydrolysis-were evaluated for potato and animal protein
      rich food rest materials. The pretreated food rest materials were used for the
      production of fungal lipid-rich biomass in submerged fermentation by the
      oleaginous fungus Mucor circinelloides. Cultivation media based on malt extract
      broth and glucose were used as controls of growth and lipid production,
      respectively. It was observed that media based on food rest materials can support
      growth and lipid production in M. circinelloides to a similar extent as the
      control media. More specifically, the use of potato hydrolysate combined with
      chicken auto-hydrolysate resulted in a higher fungal total biomass weight than
      using malt extract broth. When the same C/N ratio was used for glucose and rest
      materials-based media, similar lipid content was obtained or even higher using
      the latter media.

PMID- 29654358
TI  - Minimizing Post-operative Complications of Groin Dissection Using Modified Skin
      Bridge Technique: A Single-Centre Descriptive Study Showing Post-operative and
      Early Oncological Outcomes.
AB  - INTRODUCTION: Historically, groin dissections are associated with high morbidity.
      Various modifications have been described in the literature with inconsistent
      outcomes. The aim of this paper is to highlight modified skin bridge technique to
      minimize all post-operative complications of groin dissection without
      compromising early oncological outcomes. METHODS: A retrospective descriptive
      study of the computerized cancer database was performed to retrieve details of
      all the cancer patients who had undergone groin dissections during January 2012
      to September 2016. Data pertaining to clinical profile including demographics,
      clinical and histopathological details, treatment profile, procedure-related
      morbidity and relapse patterns were extracted and analysed. RESULTS: A total of
      75 patients underwent 105 groin dissections during this period. Out of 105 groin
      dissections, 43 were inguinal lymph node dissection (ILND) and 62 were combined
      ilio-inguinal lymph node dissection (IILND). The most common diagnosis was
      carcinoma penis (25%) followed by malignant melanoma (14.6%) and squamous cell
      carcinoma (13.33%) of lower extremities. Overall, the most common complications
      were seroma (14.28%) and skin edge necrosis (7.61%) followed by surgical site
      infection (4.76%). After a median follow-up of 17.64 months (IQR 5-61.53), a
      total of 18 patients (24%) developed recurrence. CONCLUSION: Groin dissection
      still remains an important diagnostic as well as therapeutic procedure justifying
      its potential of morbidity. Modified skin bridge technique is a very effective
      method to minimize all post-operative complications with optimal early
      oncological outcomes.

PMID- 29654359
TI  - Pseudotumor cerebri in kaposiform lymphangiomatosis: a case report and
      pathogenetic hypothesis.
AB  - CASE REPORT: A 4-year-old boy with kaposiform lymphangiomatosis (KLA) developed
      progressive headaches and papilloedema and was diagnosed with pseudotumor cerebri
      initially treated with acetazolamide. Clinical deterioration prompted placement
      of a ventriculoperitoneal shunt. After the surgery, the child's condition has
      markedly improved. DISCUSSION AND CONCLUSIONS:  A network of intracranial
      lymphatics is presently being investigated. Neuroimaging excluded KLA
      infiltration of the skull and/or meninges, leaving as the most plausible
      explanation for the child's pseudotumor cerebri the existence of an increase in
      intracranial venous pressure by venous compression at the thorax. To our
      knowledge, our case constitutes the first report of pseudotumor cerebri occurring
      in the context of KLA.

PMID- 29654360
TI  - How do cortico-striatal projections impact on downstream pallidal circuitry?
AB  - The frontal cortico-basal ganglia network plays a central role in action
      selection, associative learning, and motivation, processes requiring the
      integration of information from functionally distinct cortical regions. The
      cortico-striatal projection is a likely substrate of information integration, as
      terminal fields from different cortical regions converge in the striatum. These
      intersecting projections form complex zones of unique cortical inputs. Here, our
      goal was to follow these projection zones downstream in the basal ganglia to the
      globus pallidus. We combined a sizable database of 3D models of striato-pallidal
      chartings in macaques with maps of frontal cortical inputs to determine the
      topography of the striato-pallidal projection and the indirect cortical influence
      over the pallidum. We found that the striato-pallidal projection is highly
      topographic, with the location of the striatal injection site strongly predicting
      the location of the resulting pallidal terminal fields. Furthermore, striato
      pallidal projections are specific and largely nonoverlapping. Thus, striatal hubs
      receiving unique combinations of cortical inputs have distinct projections to the
      pallidum. However, because of the strong convergence of cortical terminal fields
      in the striatum, the indirect pallidal representation of any given frontal
      cortical region remains broad. We illustrate this arrangement by contrasting the
      pallidal projections from two nearby striatal cases: one a putative hub for
      cortical attentional bias signals, and the other with a different, more ventral
      set of cortical inputs. Thus, the striato-pallidal projection faithfully conveys
      unique combinations of cortical inputs to different locations within the pallidum
      via the striatum.

PMID- 29654361
TI  - Identification of zoonotic Giardia duodenalis in Korean native calves with normal
      feces.
AB  - Giardia duodenalis is an important zoonotic protozoan parasite that infects
      humans and other animals. This study was conducted to investigate the prevalence
      and molecular characterization of G. duodenalis infection in the feces of normal
      and diarrheic pre-weaned calves aged 1-60 days. Fecal samples were collected from
      90 Korean native calves in 7 different regions in the central region of the
      Republic of Korea (ROK). Of the 90 fecal samples, 9 (10%, 9/90) were positive for
      G. duodenalis by PCR using the beta-giardin gene. Phylogenetic analysis
      identified G. duodenalis assemblages A and E in the farms examined and G.
      duodenalis with both assemblage A and E was detected in one farm. Assemblage A
      was detected in calves with normal feces, while assemblage E was frequently
      identified in calves with diarrhea. This is the first report of the
      identification of assemblage A in pre-weaned calves with normal feces in the ROK.
      These results suggest that G. duodenalis infection is closely associated with
      calf age and management systems including overcrowding, age-mixed grouping, and
      hygiene. Thus, giardiasis in calves is an important disease because of its
      zoonotic significance and should be screened in young animals. Further studies
      are necessary to elucidate the transmission routes of zoonotic G. duodenalis
      assemblages.

PMID- 29654362
TI  - An Improved Approach for Forecasting Ecological Impacts from Future Drilling in
      Unconventional Shale Oil and Gas Plays.
AB  - Directional well drilling and hydraulic fracturing has enabled energy production
      from previously inaccessible resources, but caused vegetation conversion and
      landscape fragmentation, often in relatively undisturbed habitats. We improve
      forecasts of future ecological impacts from unconventional oil and gas play
      developments using a new, more spatially-explicit approach. We applied an energy
      production outlook model, which used geologic and economic data from thousands of
      wells and three oil price scenarios, to map future drilling patterns and evaluate
      the spatial distribution of vegetation conversion and habitat impacts. We
      forecast where future well pad construction may be most intense, illustrating
      with an example from the Eagle Ford Shale Play of Texas. We also illustrate the
      ecological utility of this approach using the Spot-tailed Earless Lizard
      (Holbrookia lacerata) as the focal species, which historically occupied much of
      the Eagle Ford and awaits a federal decision for possible Endangered Species Act
      protection. We found that ~17,000-45,500 wells would be drilled 2017-2045
      resulting in vegetation conversion of ~26,485-70,623 ha (0.73-1.96% of pre
      development vegetation), depending on price scenario ($40-$80/barrel). Grasslands
      and row crop habitats were most affected (2.30 and 2.82% areal vegetation
      reduction). Our approach improves forecasts of where and to what extent future
      energy development in unconventional plays may change land-use and ecosystem
      services, enabling natural resource managers to anticipate and direct on-the
      ground conservation actions to places where they will most effectively mitigate
      ecological impacts of well pads and associated infrastructure.

PMID- 29654363
TI  - Assessing the Hydrogeomorphic Effects of Environmental Flows using Hydrodynamic
      Modeling.
AB  - Water managers are increasingly using environmental flows (e-flows) as a tool to
      improve ecological conditions downstream from impoundments. Recent studies have
      called for e-flow approaches that explicitly consider impacts on hydrogeomorphic
      processes when developing management alternatives. Process-based approaches are
      particularly relevant in river systems that have been highly modified and where
      water supplies are over allocated. One-dimensional (1D) and two-dimensional (2D)
      hydrodynamic models can be used to resolve hydrogeomorphic processes at different
      spatial and temporal scales to support the development, testing, and refinement
      of e-flow hypotheses. Thus, the objective of this paper is to demonstrate the use
      of hydrodynamic models as a tool for assisting stakeholders in targeting and
      assessing environmental flows within a decision-making framework. We present a
      case study of e-flows on the Rio Chama in northern New Mexico, USA, where 1D and
      2D hydrodynamic modeling was used within a collaborative process to implement an
      e-flow experiment. A specific goal of the e-flow process was to improve spawning
      habitat for brown trout by flushing fine sediments from gravel features. The
      results revealed that the 2D hydrodynamic model provided much greater insight
      with respect to hydrodynamic and sediment transport processes, which led to a
      reduction in the recommended e-flow discharge. The results suggest that 2D
      hydrodynamic models can be useful tools for improving process understanding,
      developing e-flow recommendations, and supporting adaptive management even when
      limited or no data are available for model calibration and validation.

PMID- 29654364
TI  - Cognitive control over unconscious cognition: flexibility and generalizability of
      task set influences on subsequent masked semantic priming.
AB  - Recent studies using an induction task paradigm indicated that unconscious
      automatic processes underlying masked semantic priming are susceptible to
      cognitive control influences. In this paradigm, participants first perform
      different induction tasks (semantic decision vs. perceptual decision), which
      serve to activate a corresponding task set. Thereafter, the masked prime and the
      target for the lexical decision task is presented. Previously, perceptual and
      semantic induction tasks were presented in separate blocks, and the response to
      the induction task was given immediately after the inducing stimulus. The present
      study, therefore, tested two possible boundary conditions, flexibility of
      cognitive control and completeness of task set execution, for the emergence of
      task set effects on masked semantic priming. In the first experiment, perceptual
      and semantic induction tasks were presented in a randomized fashion, to assess
      whether task set influences on masked semantic priming can occur on a trial-by
      trial basis. The other two experiments tested whether task set effects on masked
      priming survive, when the response to the induction task is delayed. The present
      study yielded the same pattern of results irrespective of the variations in the
      induction task paradigm: When the masked prime was shortly presented after the
      induction task, masked semantic priming was larger subsequent to the semantic
      than subsequent to the perceptual induction task. The present study shows that
      task sets can configure unconscious processing streams rapidly on a trial-by
      trial basis and demonstrates the generalizability of cognitive control effects on
      masked semantic priming across variations of the induction task paradigm.

PMID- 29654365
TI  - Reply to the letter by Kumar and Kanchan "Age estimation based on aspartic acid
      racemization in cariesaffected teeth: need for further explorations".

PMID- 29654366
TI  - N-Acetylglucosaminidase activity, a functional trait of chitin degradation, is
      regulated differentially within two orders of ectomycorrhizal fungi: Boletales
      and Agaricales.
AB  - Chitin is one of the most abundant nitrogen-containing polymers in forest soil.
      Ability of ectomycorrhizal (EM) fungi to utilize chitin may play a key role in
      the EM symbiosis nutrition and soil carbon cycle. In forest, EM fungi exhibit
      high diversity, which could be based on function partitioning and trait
      complementarity. Although it has long been recognized that closely related
      species share functional characteristics, the phylogenetic conservatism of
      functional traits within microorganisms remains unclear. Because extracellular N
      acetylglucosaminidase activity has been proposed as functional trait of chitin
      degradation, we screened this activity on 35 EM fungi species with or without
      chitin in the growth medium to (i) describe the functional diversity of EM fungi
      and (ii) identify potential links between this functional trait and EM fungal
      phylogeny. We observed large variations of the extracellular N
      acetylglucosaminidase activities among the fungal strains. Furthermore, our
      results revealed two regulation patterns of extracellular N-acetylglucosaminidase
      activities. Indeed, these chitinolytic activities were stimulated or repressed in
      the presence of chitin, in comparison to the control treatment. These profiles of
      extracellular N-acetylglucosaminidase stimulation/repression might be conserved
      at a high phylogenetic level in the Basidiomycota phylum, as illustrated by the
      opposite patterns of regulation between Boletales and Agaricales. Finally, the
      downregulation of this activity by chitin, for some EM fungal groups, might
      suggest another chitin degradation pathway.

PMID- 29654367
TI  - Ectomycorrhizal fungal diversity and community structure associated with cork oak
      in different landscapes.
AB  - Cork oak (Quercus suber L.) forests play an important ecological and economic
      role. Ectomycorrhizal fungi (ECMF) are key components for the sustainability and
      functioning of these ecosystems. The community structure and composition of ECMF
      associated with Q. suber in different landscapes of distinct Mediterranean
      bioclimate regions have not previously been compared. In this work, soil samples
      from cork oak forests residing in different bioclimates (arid, semi-arid, sub
      humid, and humid) were collected and surveyed for ectomycorrhizal (ECM) root
      tips. A global analysis performed on 3565 ECM root tips revealed that the ECMF
      community is highly enriched in Russula, Tomentella, and Cenoccocum, which
      correspond to the ECMF genera that mainly contribute to community differences.
      The ECMF communities from the rainiest and the driest cork oak forests were
      distinct, with soils from the rainiest climates being more heterogeneous than
      those from the driest climates. The analyses of several abiotic factors on the
      ECMF communities revealed that bioclimate, precipitation, soil texture, and
      forest management strongly influenced ECMF structure. Shifts in ECMF with
      different hyphal exploration types were also detected among forests, with
      precipitation, forest system, and soil texture being the main drivers controlling
      their composition. Understanding the effects of environmental factors on the
      structuring of ECM communities could be the first step for promoting the
      sustainability of this threatened ecosystem.

PMID- 29654368
TI  - Spondylolisthesis and tumors: a treatment algorithm.
AB  - BACKGROUND: Pars defect and spondylolisthesis are frequent conditions, while bone
      tumors-particularly the primaries-are rare. The contemporary occurrence can delay
      the diagnosis of the tumor, if symptoms are considered related to
      spondylolisthesis, or can make reconstruction more demanding. To our knowledge,
      only two case reports of this contemporary occurrence have been published in the
      literature. Being such rare, guidelines on surgical treatment have not been
      proposed yet. MATERIALS AND METHODS: A retrospective review of patients treated
      for spine bone tumors by the senior author from 1990 to 2017 was performed to
      find cases of contemporary occurrence of spondylolisthesis and/or pars defect and
      spine bone tumors. General health data, radiological imaging, histological tumor
      diagnosis, treatment, and follow-up were analyzed and discussed. RESULTS: Among
      the 1870 patients treated for spinal tumors between 1990 and 2017 by the senior
      author, 14 cases of association between tumors and
      spondylolysis/spondylolisthesis were observed. The cohort includes five males
      (35.7%) and nine females (64.3%), aged 14-72. Mean age of patients at surgery
      time was 47. CONCLUSIONS: Interactions between spondylolisthesis and bone tumors
      of the spine are episodic. These two conditions rarely occur in the same patient.
      No treatment strategy has been described until now. The target of this paper is
      to propose an algorithm to surgically treat patients with concomitant bone tumor
      and spondylolisthesis. This classification identifies a treatment-oriented
      algorithm based on two major categories: type A, bone tumor arising on the same
      vertebra or to an adjacent level; type B, bone tumor arising at least one unit
      far from the spondylolisthesis. This algorithm can help the surgeon facing this
      rare combination of diseases in the appropriate preoperative planning. These
      slides can be retrieved under Electronic Supplementary Material.

PMID- 29654369
TI  - Pedicle screw loosening is correlated to chronic subclinical deep implant
      infection: a retrospective database analysis.
AB  - PURPOSE: Spinal fusion is used for treatment of spinal deformities, degeneration,
      infection, malignancy, and trauma. Reduction of motion enables osseous fusion and
      permanent stabilization of segments, compromised by loosening of the pedicle
      screws (PS). Deep implant infection, biomechanical, and chemical mechanisms are
      suspected reasons for loosening of PS. Study objective was to investigate the
      frequency and impact of deep implant infection on PS loosening. METHODS:
      Intraoperative infection screening from wound and explanted material sonication
      was performed during revision surgeries following dorsal stabilization. Case
      history events and factors, which might promote implant infections, were included
      in this retrospective survey. RESULTS: 110 cases of spinal metal explantation
      were included. In 29.1% of revision cases, infection screening identified a germ,
      most commonly Staphylococcus (53.1%) and Propionibacterium (40.6%) genus.
      Patients screened positive had a significant higher number of previous spinal
      operations and radiologic loosening of screws. Patients revised for adjacent
      segment failure had a significantly lower rate of positive infection screening
      than patients revised for directly implant associated reasons. Removal of
      implants that revealed positive screening effected significant pain relief.
      CONCLUSIONS: Chronic implant infection seems to play a role in PS loosening and
      ongoing pain, causing revision surgery after spinal fusion. Screw loosening and
      multiple prior spinal operations should be suspicious for implant infection after
      spinal fusion when it comes to revision surgery. These slides can be retrieved
      under Electronic Supplementary Material.

PMID- 29654370
TI  - Progression of urothelial carcinoma in situ of the urinary bladder: a switch from
      luminal to basal phenotype and related therapeutic implications.
AB  - The stratification of bladder cancer into luminal and basal tumors has recently
      been introduced as a novel prognostic system in patient cohorts of muscle
      invasive bladder cancer or high-grade papillary carcinomas. Using a
      representative immunohistochemistry panel, we analyzed luminal and basal marker
      expression in a large case series (n = 156) of urothelial carcinoma in situ
      (CIS), a precancerous lesion that frequently progresses to muscle-invasive
      disease. The majority of CIS cases was characterized by a positivity for luminal
      markers (aberrant cytokeratin (CK) 20 85% (132/156), GATA3 median Remmele score
      (score of staining intensity (0-3) multiplied with percentage of positive cells
      (0-4)): 12, estrogen receptor (ER) beta Remmele score > 2: 88% (138/156), human
      epidermal growth factor receptor 2 (Her2) Dako score 3+ 32% (50/156), Her2 Dako
      score 2+ 33% (51/156)), and marginal expression of basal markers (CK5/6+ 2%
      (3/156), CK14+ 1% (2/156)). To further investigate phenotypic stability during
      disease progression, we compared 48 pairs of CIS and invasive tumors from the
      same biopsy. A highly significant loss of luminal marker expression (p < 0.001)
      was observed in the course of progression whereas an increase of basal marker
      expression (p < 0.01) was noted in the invasive compartment. Importantly, 91% of
      CIS cases demonstrated a positivity for at least one of the two predictive
      markers Her2 and ERbeta, indicating that the analysis of Her2 and ERbeta may help
      to identify CIS-patient subgroups prone to more efficient targeted treatment
      strategies. Larger prospective and biomarker-embedded clinical trials are needed
      to confirm and validate our preliminary findings.

PMID- 29654371
TI  - Silver ciprofloxacin (CIPAG): a successful combination of chemically modified
      antibiotic in inorganic-organic hybrid.
AB  - The new silver(I) ionic, water soluble, compound {[Ag(CIPH)2]NO3?0.75MeOH?1.2H2O}
      (CIPAG) was obtained by reacting silver(I) nitrate with the antibiotic
      ciprofloxacin (CIPH). The complex was characterized by m.p., mid-FT-IR, 1H-NMR,
      UV-Vis spectroscopic techniques. The crystal structures of both CIPAG and the
      hexahydrated neutral free drug {[CIPH]?6(H2O)} (2) were characterized by X-ray
      crystallography. Two neutral ligands are datively bonded to the metal ion through
      the piperidinic nitrogen atoms forming a cationic {[Ag(CIPH)2]+} counter part
      which is neutralized by a nitrate group. The antibacterial effect of CIPAG and
      the commercially available hydrochloric salt of the antibiotic ({[CIPH 2+ ]?Cl -
      } (3)) were tested against the bacterial species Pseudomonas aeruginosa (PAO1),
      Staphylococcus epidermidis (St. epidermidis) and Staphylococcus aureus (St.
      aureus) by the mean of minimum inhibitory concentration, minimum bactericidal
      concentration and their inhibitory zone (IZ). The influence of CIPAG and 3
      against the formation of biofilm of PAO1 or St. aureus was also evaluated by mean
      of biofilm elimination concentration. The IZ caused by CIPAG which has been
      loaded in poly-hydroxyethylmethacrylate, is determined. The genotoxicity of CIPAG
      and 3 is tested in vitro against normal human corneal epithelial cells (HCET
      cells), by the presence of micronucleus in HCET cells and in vivo by mean of
      Allium cepa test.

PMID- 29654372
TI  - Aptamer based label free thrombin assay based on the use of silver nanoparticles
      incorporated into self-polymerized dopamine.
AB  - The authors describe an electrochemical aptasensor for thrombin that is based on
      the use of a glassy carbon electrode (GCE) modified with polydopamine that is
      loaded with silver nanoparticles (PDA/AgNPs). The use of AgNPs improves the
      conductivity of the film and increases the surface area of the GCE. PDA was
      deposited on the GCE via self-polymerization, and the thrombin binding aptamer
      was grafted onto the PDA-modified GCE by a single step reaction. Residual
      electrode surface was blocked with 6-mercapto-1-hexanol. On exposure to thrombin,
      the electrochemical impedance of the modified electrode increases gradually.
      Response is linear in the 0.1 pM to 5.0 nM thrombin concentration range, and the
      limit of detection is as low as 36 fM. The method is selective and capable of
      detecting thrombin in diluted human serum. In our perception, such a GCE modified
      with AgNP in a PDA matrix may be applied to many other analytes for which
      appropriate aptamers are available. Graphical abstract Schematic of an
      electrochemical aptasensor for sensitive and selective thrombin detection based
      on the use of a self-polymerized polydopamine film loaded with silver
      nanoparticles.

PMID- 29654373
TI  - An Adaptive Monitoring Scheme for Automatic Control of Anaesthesia in dynamic
      surgical environments based on Bispectral Index and Blood Pressure.
AB  - During surgical procedures, bispectral index (BIS) is a well-known measure used
      to determine the patient's depth of anesthesia (DOA). However, BIS readings can
      be subject to interference from many factors during surgery, and other parameters
      such as blood pressure (BP) and heart rate (HR) can provide more stable
      indicators. However, anesthesiologist still consider BIS as a primary measure to
      determine if the patient is correctly anaesthetized while relaying on the other
      physiological parameters to monitor and ensure the patient's status is
      maintained. The automatic control of administering anesthesia using intelligent
      control systems has been the subject of recent research in order to alleviate the
      burden on the anesthetist to manually adjust drug dosage in response
      physiological changes for sustaining DOA. A system proposed for the automatic
      control of anesthesia based on type-2 Self Organizing Fuzzy Logic Controllers (T2
      SOFLCs) has been shown to be effective in the control of DOA under simulated
      scenarios while contending with uncertainties due to signal noise and dynamic
      changes in pharmacodynamics (PD) and pharmacokinetic (PK) effects of the drug on
      the body. This study considers both BIS and BP as part of an adaptive automatic
      control scheme, which can adjust to the monitoring of either parameter in
      response to changes in the availability and reliability of BIS signals during
      surgery. The simulation of different control schemes using BIS data obtained
      during real surgical procedures to emulate noise and interference factors have
      been conducted. The use of either or both combined parameters for controlling the
      delivery Propofol to maintain safe target set points for DOA are evaluated. The
      results show that combing BIS and BP based on the proposed adaptive control
      scheme can ensure the target set points and the correct amount of drug in the
      body is maintained even with the intermittent loss of BIS signal that could
      otherwise disrupt an automated control system.

PMID- 29654374
TI  - Sequencing, genome analysis and host range of a novel Ralstonia phage, RsoP1EGY,
      isolated in Egypt.
AB  - A novel Ralstonia phage was isolated from soil in Egypt. It was designated
      Ralstonia phage RsoP1EGY using our phage identifier naming approach to reflect
      the phage's bacterial host species, characteristics and origin. When tested, this
      phage specifically infected only race 3 biovar 2 phylotype IIB sequevar 1, and
      not non-race 3 biovar 2 strains of Ralstonia solanacearum. The phage has an
      icosahedral capsid of 60 +/- 5 nm in diameter with a short tail of 15 +/- 5 nm in
      length, typical of a podovirus. The genome of RsoP1EGY is 41,297 bp in size,
      containing 50 open reading frames, with no significant sequence identity to any
      other reported R. solanacearum or non-Ralstonia phages, except to the recently
      deposited but unreported and unclassified Ralstonia phage DU_RP_I. RsoP1EGY is
      the first sequenced and characterized R. solanacearum phage isolated in Egypt.

PMID- 29654375
TI  - Validation of a Sulfuric Acid Digestion Method for Inductively Coupled Plasma
      Mass Spectrometry Quantification of TiO2 Nanoparticles.
AB  - A consistent analytical method incorporating sulfuric acid (H2SO4) digestion and
      ICP-MS quantification has been developed for TiO2 quantification in biotic and
      abiotic environmentally relevant matrices. Sample digestion in H2SO4 at 110
      degrees C provided consistent results without using hydrofluoric acid or
      microwave digestion. Analysis of seven replicate samples for four matrices on
      each of 3 days produced Ti recoveries of 97% +/- 2.5%, 91 % +/- 4.0%, 94% +/-
      1.8%, and 73 % +/- 2.6% (mean +/- standard deviation) from water, fish tissue,
      periphyton, and sediment, respectively. The method demonstrated consistent
      performance in analysis of water collected over a 1 month.

PMID- 29654377
TI  - Spouses, social networks and other upstream determinants of type 2 diabetes
      mellitus.
AB  - Diabetes risk factors outside the individual are receiving increasing attention.
      In this issue of Diabetologia, Nielsen et al (DOI: https://doi.org/10.1007/s00125
      018-4587-1 ) demonstrate that an individual's obesity level is associated with
      incident type 2 diabetes in their spouse. This is in line with studies providing
      evidence for spousal and peer similarities in lifestyle behaviours and obesity.
      Non-random mating and convergence over time are two explanations for this
      phenomenon, but shared exposure to more upstream drivers of diabetes may also
      play a role. From a systems-science perspective, these mechanisms are likely to
      occur simultaneously and interactively as part of a complex system. In this
      commentary, we provide an overview of the wider system-level factors that
      contribute to type 2 diabetes.

PMID- 29654378
TI  - [Do we have the caring relatives of dementia patients in mind?]

PMID- 29654376
TI  - Persistence of abnormalities in white matter in children with type 1 diabetes.
AB  - AIMS/HYPOTHESIS: Prior studies suggest white matter growth is reduced and white
      matter microstructure is altered in the brains of young children with type 1
      diabetes when compared with brains of non-diabetic children, due in part to
      adverse effects of hyperglycaemia. This longitudinal observational study examines
      whether dysglycaemia alters the developmental trajectory of white matter
      microstructure over time in young children with type 1 diabetes. METHODS: One
      hundred and eighteen children, aged 4 to <10 years old with type 1 diabetes and
      58 age-matched, non-diabetic children were studied at baseline and 18 months, at
      five Diabetes Research in Children Network clinical centres. We analysed
      longitudinal trajectories of white matter using diffusion tensor imaging.
      Continuous glucose monitoring profiles and HbA1c levels were obtained every 3
      months. RESULTS: Axial diffusivity was lower in children with diabetes at
      baseline (p = 0.022) and at 18 months (p = 0.015), indicating that differences in
      white matter microstructure persist over time in children with diabetes. Within
      the diabetes group, lower exposure to hyperglycaemia, averaged over the time
      since diagnosis, was associated with higher fractional anisotropy (p = 0.037).
      Fractional anisotropy was positively correlated with performance (p < 0.002) and
      full-scale IQ (p < 0.02). CONCLUSIONS/INTERPRETATION: These results suggest that
      hyperglycaemia is associated with altered white matter development, which may
      contribute to the mild cognitive deficits in this population.

PMID- 29654379
TI  - Bioencapsulation and Colonization Characteristics of Lactococcus lactis subsp.
      lactis CF4MRS in Artemia franciscana: a Biological Approach for the Control of
      Edwardsiellosis in Larviculture.
AB  - Predominance of beneficial bacteria helps to establish a healthy microbiota in
      fish gastrointestinal system and thus to reduce emerging pathogen. In this study,
      the colonization efficacy of Lactococcus lactis subsp. lactis CF4MRS in Artemia
      franciscana and its potential as a probiotic in suppressing Edwardsiella sp.
      infection were investigated in vivo. The colonization extent of the
      bioencapsulated L. lactis was established through visualization of gfp gene
      transformed L. lactis in A. franciscana. Here, we demonstrate that when A.
      franciscana is administrated with L. lactis at 108 CFU mL-1 for 8 h, the highest
      relative percentage of survival (RPS = 50.0) is observed after inoculation with
      Edwardsiella sp. The total counts of L. lactis entrapped in Artemia were the
      highest (ranged from 3.2 to 5.1 * 108 CFU mL-1), when 108-109 CFU mL-1 of L.
      lactis was used as starting inoculum, with the bioencapsulation performed within
      8-24 h. Fluorescent microscopy showed gfp-transformed L. lactis colonized the
      external trunk surfaces, mid-gut and locomotion antennules of the A. franciscana
      nauplii. These illustrations elucidate the efficiency of colonization of L.
      lactis in the gastrointestinal tract and on the body surfaces of Artemia. In
      conclusion, L. lactis subsp. lactis CF4MRS shows a good efficacy of colonization
      in Artemia and has the potential for biocontrol/probiotic activity against
      Edwardsiella sp. infection.

PMID- 29654380
TI  - Heart rate variability and baroreflex sensitivity abnormalities in Guillain-Barre
      syndrome: a pilot study.
AB  - OBJECTIVE: The current study aimed to investigate autonomic dysfunction in
      Guillain-Barre syndrome (GBS) patients and describe the results of computational
      heart rate variability (HRV)/baroreflex sensitivity (BRS) and autonomic challenge
      tests. METHODS: GBS patients were consecutively recruited and the results were
      compared to age- and gender-matched healthy controls. A series of autonomic
      function tests including computation-dependent tests (power spectrum analysis of
      HRV and BRS at rest) and challenge maneuvers (deep breathing, eyeball
      compression, active standing, the Valsalva maneuver, sustained handgrip, and the
      cold pressor test) were performed. RESULTS: Ten GBS patients (six men; mean age =
      40.1 +/- 13.9 years) and ten gender- and age-matched healthy controls were
      recruited. The mean GBS functional grading scale at disease plateau was 3.4 +/-
      1.0. No patients required intensive care unit admission or mechanical
      ventilation. Low-frequency HRV (p = 0.027), high-frequency HRV (p = 0.008), and
      the total power spectral density of HRV (p = 0.015) were significantly reduced in
      patients compared to controls. The mean up slope (p = 0.034), down slope (p =
      0.011), and total slope (p = 0.024) BRS were significantly lower in GBS patients.
      The diastolic rise in blood pressure in the cold pressor test was significantly
      lower in GBS patients compared to controls (p = 0.008). INTERPRETATION:
      Computation-dependent tests (HRV and BRS) were more useful for detecting
      autonomic dysfunction in GBS patients, whereas the cold pressor test was the only
      reliable challenge test, making it useful as a bedside measure of autonomic
      function in GBS patients.

PMID- 29654381
TI  - Renal Effects of Incretin-Based Diabetes Therapies: Pre-clinical Predictions and
      Clinical Trial Outcomes.
AB  - PURPOSE OF REVIEW: The purpose of this review is to correlate predictions based
      on pre-clinical data with outcomes from clinical trials that examine the effects
      of incretin-based diabetes treatments on the kidney. The incretin-based
      treatments include agonists of the glucagon-like peptide 1 receptor (GLP-1R) and
      inhibitors of the enzyme, dipeptidyl peptidase-4 (DPP-4). In addition, what is
      known about the incretin-based therapies will be compared to what is known about
      the renal effects of SGLT2 inhibitors. RECENT FINDINGS: Large-scale clinical
      trials have shown that SGLT2 inhibitors reduce albuminuria and preserve estimated
      glomerular filtration rate (eGFR) in patients with diabetic nephropathy. A
      concise and plausible hemodynamic mechanism is supported by pre-clinical research
      on the physiology and pharmacology of SGLT2. Large-scale clinical trials have
      shown that incretin-based therapies mitigate albuminuria but have not shown
      beneficial effects on eGFR. Research on the incretin-based therapies has yielded
      a diverse array of direct effects throughout the body, which fuels speculation as
      to how these drugs might benefit the diabetic kidney and affect its function(s).
      But in vivo experiments have yet to confirm that the proposed mechanisms
      underlying emergent phenomena, such as proximal tubular fluid reabsorption, are
      the ones predicted by cell and molecular experiments. There may be salutary
      effects of incretin-based treatments on the diabetic kidney, but the system is
      complex and not amenable to simple explanation or prior prediction. This
      contrasts with the renal effects of SGLT2 inhibitors, which can be explained
      concisely.

PMID- 29654383
TI  - Alternative Reservoir and Balloon Placement in Complex Patients Undergoing
      Urologic Prostheses.
AB  - PURPOSE OF REVIEW: To evaluate contemporary rationale and techniques for ectopic
      reservoir/balloon placement in complex urologic prosthetics patients. RECENT
      FINDINGS: Recent studies have demonstrated that ectopic reservoir placement is
      safe and durable when compared to traditional space of Retzius placement. Complex
      patients exist on a spectrum from those with a previously violated retropubic
      space, to those with bilaterally obscured external inguinal rings and/or multiple
      prior prosthetic reservoirs. Ectopic placement has become more commonplace and
      accepted as a viable alternative strategy over the past 7 years. Concerns
      relating to reservoir palpability and long-term outcomes have been allayed. The
      risk of deep pelvic complications appears to be negligible after both placement
      or removal of ectopic reservoirs when performed by experienced implanters even in
      the most complex patient. Ectopic placement of prosthetic balloons and reservoirs
      offers unique advantages and has become commonplace in contemporary prosthetic
      urology practice.

PMID- 29654382
TI  - Expanding lysine industry: industrial biomanufacturing of lysine and its
      derivatives.
AB  - L-Lysine is widely used as a nutrition supplement in feed, food, and beverage
      industries as well as a chemical intermediate. At present, great efforts are made
      to further decrease the cost of lysine to make it more competitive in the
      markets. Furthermore, lysine also shows potential as a feedstock to produce other
      high-value chemicals for active pharmaceutical ingredients, drugs, or materials.
      In this review, the current biomanufacturing of lysine is first presented.
      Second, the production of novel derivatives from lysine is discussed. Some
      chemicals like L-pipecolic acid, cadaverine, and 5-aminovalerate already have
      been obtained at a lab scale. Others like 6-aminocaproic acid, valerolactam, and
      caprolactam could be produced through a biological and chemical coupling pathway
      or be synthesized by a hypothetical pathway. This review demonstrates an active
      and expansive lysine industry, and these green biomanufacturing strategies could
      also be applied to enhance the competitiveness of other amino acid industry.

PMID- 29654384
TI  - Quantitative Dual Contrast CT Technique for Evaluation of Articular Cartilage
      Properties.
AB  - Impact injuries of cartilage may initiate post-traumatic degeneration, making
      early detection of injury imperative for timely surgical or pharmaceutical
      interventions. Cationic (positively-charged) CT contrast agents detect loss of
      cartilage proteoglycans (PGs) more sensitively than anionic (negatively-charged)
      or non-ionic (non-charged, i.e., electrically neutral) agents. However,
      degeneration related loss of PGs and increase in water content have opposite
      effects on the diffusion of the cationic agent, lowering its sensitivity. In
      contrast to cationic agents, diffusion of non-ionic agents is governed only by
      steric hindrance and water content of cartilage. We hypothesize that sensitivity
      of an iodine(I)-based cationic agent may be enhanced by simultaneous use of a non
      ionic gadolinium(Gd)-based agent. We introduce a quantitative dual energy CT
      technique (QDECT) for simultaneous quantification of two contrast agents in
      cartilage. We employ this technique to improve the sensitivity of cationic CA4+
      (q =+4) by normalizing its partition in cartilage with that of non-ionic
      gadoteridol. The technique was evaluated with measurements of contrast agent
      mixtures of known composition and human osteochondral samples (n = 57) after
      immersion (72 h) in mixture of CA4+ and gadoteridol. Samples were
      arthroscopically graded and biomechanically tested prior to QDECT (50/100 kV).
      QDECT determined contrast agent mixture compositions correlated with the true
      compositions (R2= 0.99, average error = 2.27%). Normalizing CA4+ partition in
      cartilage with that of gadoteridol improved correlation with equilibrium modulus
      (from rho = 0.701 to 0.795). To conclude, QDECT enables simultaneous
      quantification of I and Gd contrast agents improving diagnosis of cartilage
      integrity and biomechanical status.

PMID- 29654386
TI  - Guided bone regeneration in calvarial critical size bony defect using a double
      layer resorbable collagen membrane covering a xenograft: a histological and
      histomorphometric study in rats.
AB  - PURPOSE: The aim of the present study was to evaluate histologically and
      histomorphometrically the bone regeneration in critical size calvarial defects in
      rats grafted with either a deproteinized bovine bone mineral (DBBM) alone or in
      combination with a single or double layer of native bilayer collagen membrane
      (NBCM). The secondary objective was to evaluate histologically and
      histomorphometrically the residual DBBM in these defects. MATERIAL AND METHODS:
      Thirty-two Wistar rats were divided into two groups: a control group of 16 rats
      with two critical size calvarial defects (CSD) of 5 mm performed each on either
      side of the median sagittal suture, where the frontal defect remained without any
      filling (negative control), while the occipital defect (positive control) was
      filled with DBBM; and then a test group of 16 rats, with two CSD filled with DBBM
      and covered by either a single (SM) or a double layer (DM) of NBCM. The animals
      were sacrificed at 4 and 8 weeks. RESULTS: At 1 month, the histological and
      histomorphometric analysis showed new bone formation (NBF) in the defects that
      received only DBBM, DBBM+DM, and DBBM+SM (11.5, 17.3, and 22.7%, respectively),
      while the negative control defects showed only 0.4% of new bone formation. At 2
      months, the histological and histomorphometric analysis showed NBF in the defects
      that received only DBBM, DBBM+DM, and DBBM+SM (16.8, 24.5, and 37%,
      respectively), while the negative control defects showed only 0.9% of new bone
      formation. The residual xenogeneic material (RXM) was higher in defects covered
      by SM (30.2% at 1 month and 25.3% at 2 months) or DM (32.5% at 1 month and 28.5%
      at 2 months) compared with defects that were not covered by membranes (15.3% at 1
      month and 9.4% at 2 months). CONCLUSIONS: This study demonstrated that GBR with a
      xenogeneic material in rat calvarial (CSD) of 5 mm requires the application of
      resorbable collagen membranes in either single or double layer, and a single
      layer alone is sufficient to promote this regeneration.

PMID- 29654385
TI  - Recognizable phenotypes in CDG.
AB  - Pattern recognition, using a group of characteristic, or discriminating features,
      is a powerful tool in metabolic diagnostic. A classic example of this approach is
      used in biochemical analysis of urine organic acid analysis, where the reporting
      depends more on the correlation of pertinent positive and negative findings,
      rather than on the absolute values of specific markers. Similar uses of pattern
      recognition in the field of biochemical genetics include the interpretation of
      data obtained by metabolomics, like glycomics, where a recognizable pattern or
      the presence of a specific glycan sub-fraction can lead to the direct diagnosis
      of certain types of congenital disorders of glycosylation. Another indispensable
      tool is the use of clinical pattern recognition-or syndromology-relying on
      careful phenotyping. While genomics might uncover variants not essential in the
      final clinical expression of disease, and metabolomics could point to a mixture
      of primary but also secondary changes in biochemical pathways, phenomics
      describes the clinically relevant manifestations and the full expression of the
      disease. In the current review we apply phenomics to the field of congenital
      disorders of glycosylation, focusing on recognizable differentiating findings in
      glycosylation disorders, characteristic dysmorphic features and malformations in
      PMM2-CDG, and overlapping patterns among the currently known glycosylation
      disorders based on their pathophysiological basis.

PMID- 29654387
TI  - Serum chloride levels in critical illness-the hidden story.

PMID- 29654388
TI  - Insulin-mimetic effects of short-term rapamycin in type 1 diabetic patients prior
      to islet transplantation.
AB  - BACKGROUND: The immunosuppressive drug rapamycin may influence insulin
      sensitivity in insulin-responsive tissues. AIMS: This study aimed at evaluating
      the effectiveness of rapamycin pre-treatment before pancreatic islet
      allotransplantation (ITx) in patients with type 1 diabetes mellitus (T1DM).
      METHODS: Forty-one T1DM patients were studied. Thirteen patients with poor
      glycemic control underwent a short-term rapamycin treatment before ITx (Group 1),
      and they were compared to 28 patients undergoing ITx without rapamycin pre
      treatment (Group 2). Outcomes were daily insulin requirement (DIR), fasting blood
      glucose, HbA1c, C-peptide and the SUITO index of beta-cell function. A subgroup
      of patients pre-treated with rapamycin before ITx underwent euglycemic
      hyperinsulinemic clamp with [6,6-2H2] glucose before and after ITx to evaluate
      insulin sensitivity. RESULTS: We found a significant reduction in DIR after
      rapamycin pre-treatment (- 8 +/- 6 U/day, mean +/- SD, p < 0.001) and 1 year
      after ITx. DIR reduction 1 year after ITx was greater in Group 1 as compared to
      Group 2 (- 37 +/- 15 vs. - 19 +/- 13 U/day, p = 0.005) and remained significant
      after adjusting for gender, age, glucose and baseline HbA1c (beta = 18.2 +/- 5.9,
      p = 0.006). Fasting glucose and HbA1c significantly decreased 1 year after ITx in
      Group 1 (HbA1c: - 2.1 +/- 1.4%, p = 0.002), while fasting C-peptide (+0.5 +/- 0.3
      nmol/l, p = 0.002) and SUITO index increased (+57.4 +/- 39.7, p = 0.016), without
      differences between the two groups. Hepatic glucose production decreased after
      rapamycin pre-treatment (- 1.1 +/- 1.1 mg/kg/min, p = 0.04) and after ITx (- 1.6
      +/- 0.6 mg/kg/min, p = 0.015), while no changes in peripheral glucose disposal
      were observed. CONCLUSIONS: Rapamycin pre-treatment before ITx succeeds in
      reducing insulin requirement, enhancing hepatic insulin sensitivity. This
      treatment may improve short-term ITx outcomes, possibly in selected patients with
      T1DM complicated by insulin resistance. CLINICAL TRIAL: Clinicaltrials.gov
      NCT01060605; NCT00014911.

PMID- 29654389
TI  - [Long-term effects of anti-VEGF therapy for retinopathy of prematurity].
AB  - BACKGROUND: Intravitreal anti-VEGF therapy is a highly efficacious new treatment
      option for retinopathy of prematurity (ROP) with significant advantages over
      conventional therapy using retinal laser coagulation in selected cases. With
      growing experience in the clinical application over the last years, data about
      the potential long-term effects of this therapeutic approach are increasingly
      becoming available, such as those related to ROP-associated myopia,
      neurodevelopment and late recurrences of ROP. Knowledge of these effects is of
      direct relevance for the clinical management of affected children. METHODS: The
      article is based on a literature review of the covered topics. RESULTS: In
      addition to its therapeutic effect on retinal pathology, anti-VEGF therapy in ROP
      can also reduce ROP-associated myopia, most likely due to a normalization of
      anterior segment development. As the unresolved question of potential negative
      effects of bevacizumab on neurodevelopment remains of concern, the use of
      alternative treatment options, such as ranibizumab or laser coagulation should be
      considered. Treatment-requiring recurrences of ROP following anti-VEGF therapy
      have been reported as late as 69 weeks postmenstrual age, indicating that long
      term frequent ophthalmological follow-up examinations are required. CONCLUSION:
      Long-term effects of anti-VEGF therapy in ROP differ significantly from
      alternative treatment options such as laser coagulation. These differences are of
      relevance for the choice of treatment modality and the follow-up regimen of
      treated children.

PMID- 29654390
TI  - [Rheumatology in the mirror of media and advertising exemplified by the
      Rheumazentrum Rhein-Ruhr].

PMID- 29654391
TI  - [Autologous stem cell transplantation with a myeloablative regimen for treatment
      of severe systemic sclerosis].

PMID- 29654392
TI  - [Research consortium Neuroimmunology and pain in the research network
      musculoskeletal diseases].
AB  - BACKGROUND: The research consortium Neuroimmunology and Pain (Neuroimpa) explores
      the importance of the relationships between the immune system and the nervous
      system in musculoskeletal diseases for the generation of pain and for the course
      of fracture healing and arthritis. MATERIAL AND METHODS: The spectrum of methods
      includes analyses at the single cell level, in vivo models of arthritis and
      fracture healing, imaging studies on brain function in animals and humans and
      analysis of data from patients. RESULTS: Proinflammatory cytokines significantly
      contribute to the generation of joint pain through neuronal cytokine receptors.
      Immune cells release opioid peptides which activate opioid receptors at
      peripheral nociceptors and thereby evoke hypoalgesia. The formation of new bone
      after fractures is significantly supported by the nervous system. The sympathetic
      nervous system promotes the development of immune-mediated arthritis. The studies
      show a significant analgesic potential of the neutralization of proinflammatory
      cytokines and of opioids which selectively inhibit peripheral neurons.
      Furthermore, they show that the modulation of neuronal mechanisms can
      beneficially influence the course of musculoskeletal diseases. DISCUSSION:
      Interventions in the interactions between the immune system and the nervous
      system hold a great therapeutic potential for the treatment of musculoskeletal
      diseases and pain.

PMID- 29654393
TI  - Psychiatric Emergency Services - Can Duty-Hour Changes Help Residents and
      Patients?
AB  - Limitations on resident duty hours have been widely introduced with the intention
      of decreasing resident fatigue and improving patient outcomes. While there is
      evidence of improvement in resident well-being and education following such
      initiatives, they have inadvertently resulted in increased number of hand-offs
      between clinicians leading to potential errors in patient care. Current
      literature emphasizes need for more specialty/setting-specific scheduling, while
      considering residents' opinions when implementing duty-hour reforms. There are no
      reports examining the impact of duty-hour changes on residents or patients in
      psychiatric emergency service (PES) settings. Our purpose was to assess the
      impact of a recent scheduling change and decrease in overall duty hours, on
      resident well-being and sense of burnout, while also evaluating changes to
      patient wait-time and length of stay (LOS) in PES. Residents completed Maslach
      Burnout Inventory and anonymous surveys focusing on: fatigue, sleep, life outside
      work for shifts - regular (8 am-8 pm) and swing shifts (12 pm-10 pm). Data from
      the electronic medical records were collected for 6 months pre- and post-schedule
      change (January 2016-February 2017), for LOS and patient wait-time. Residents'
      preference for shifts was split. However, 86% reported getting enough sleep
      during swing shifts, while 83% reported lack of sleep during regular shifts. The
      average patient wait-time and LOS significantly decreased from 169 to 147 and 690
      to 515 min, respectively. The change to swing shifts significantly impacts LOS
      and patient wait-time. The short shifts demonstrated an improvement in well-being
      for residents, but were not the singular factor for overall resident
      satisfaction.

PMID- 29654394
TI  - Investigating clinical failure of core decompression with autologous bone marrow
      mononuclear cells grafting for the treatment of non-traumatic osteonecrosis of
      the femoral head.
AB  - OBJECTIVE: This study aimed to analyze the clinical factors related to the
      failure of autologous bone marrow mononuclear cells grafting (BMMCG) following
      core decompression (CD) in early stage osteonecrosis of the femoral head (ONFH).
      METHODS: In total, 148 patients (192 hips) underwent CD with autologous BMMCG for
      treatment of non-traumatic ONFH. The patients were classified by their ARCO
      staging and China-Japan Friendship Hospital (CJFH) typing system. All patients
      were clinically and radiographically followed up every three months during the
      first year and every six months in the following years. The clinical evaluation
      was conducted by pre- and post-operative Harris hip scores (HHS), while serial
      anteroposterior (AP) and frog lateral radiographs were used for post-operative
      radiographic evaluation. RESULTS: There were 56 hips as clinical failure cases,
      and 50 hips (89.29%) of failure cases developed between three and ten months
      after operation. Based on CJFH classification system, type L2 showed more failure
      rate with 60.0% (9 of15). The Cox risk model showed that disease type was an
      independent risk factor for post-operative clinical failure (P = 0.042).
      Multivariate analysis of the Cox proportional-hazards model showed that type L1
      had a hazard ratio (HR) of 0.286 (95% CI 0.100-0.816), type L3 with HR of 0.245
      (95% CI 0.079-0.759), respectively. CONCLUSION: Disease type is an important risk
      factor for autologous BMMCG combined with CD, and the degree of lateral pillar
      necrosis is a significant reference index for prognosis evaluation in early stage
      of ONFH.

PMID- 29654397
TI  - Self-Reported Interest to Participate in a Health Survey if Different Amounts of
      Cash or Non-Monetary Incentive Types Were Offered.
AB  - The objective of this study was to assess monetary and non-monetary factors that
      can influence the decision to participate in a future health survey. A
      questionnaire was administered to eligible, low-income participants (n = 1502) of
      the 2012 Los Angeles County Health and Nutrition Examination Survey (LAHANES-II).
      Multivariable regression analyses were performed to describe factors potentially
      associated with future intent to participate in similar survey designs. The
      results of the survey suggest that, overall, female participants had a greater
      interest in participating under a variety of incentive scenarios. Compared to the
      25-34 age group, older participants (35-44, 45-84) reported more interest to
      participate if $10 cash [prepaid gift/debit card], a coupon for product/travel,
      or a small item [e.g., granola bar, t-shirt, pen] was offered, whereas younger
      participants (18-24) reported greater interest for $25 cash or a coupon for
      product/travel. Non-Whites, when compared to Whites/Non-Hispanics, reported
      greater interest to participate if any of the incentives was offered. High school
      graduates, when compared to those with some college education, reported greater
      interest to participate if $10 cash, a small item, or a lottery ticket was
      offered. Presence of two or more chronic conditions increased interest while
      concerns about participation in LAHANES-II was associated with reduced interest
      to participate in future health-related surveys. The results suggest that both
      incentives and non-monetary considerations (e.g., personal concerns about
      participating and individual level characteristics) can influence the decision to
      participate in health-related surveys and offer insights into strategies that can
      improve response rates for these assessments that are often used to inform
      community planning.

PMID- 29654395
TI  - The association of serum angiogenic growth factors with renal structure and
      function in patients with adult autosomal dominant polycystic kidney disease.
AB  - PURPOSE: Autosomal dominant polycystic kidney disease (ADPKD) is a common
      congenital chronic kidney disease (CKD). We report here the relationship of serum
      angiopoietin-1 (Ang-1), Ang-2, and vascular endothelial growth factor (VEGF) with
      total kidney volume (TKV), total cyst volume (TCV), and renal failure in adult
      ADPKD patients at various stages of CKD. METHODS: This cross-sectional study was
      conducted with 50 patients diagnosed with ADPKD and a control group of 45 age
      matched healthy volunteers. In patient group, TKV and TCV were determined with
      upper abdominal magnetic resonance imaging, whereas in controls, TKV was
      determined with ultrasonography according to ellipsoid formula. Renal function
      was assessed with serum creatinine, estimated glomerular filtration rate (eGFR),
      and spot urinary protein/creatinine ratio (UPCR). Ang-1, Ang-2, and VEGF were
      measured using enzyme-linked immunosorbent assay. RESULTS: Patients with ADPKD
      had significantly higher TKV (p < 0.001) and UPCR (p < 0.001), and lower eGFR (p
      <= 0.001) compared to the controls. Log10Ang-2 was found to be higher in ADPKD
      patients at all CKD stages. Multiple linear regression analysis showed that there
      was no association between log10Ang-1, log10Ang-2, or log10VEGF and creatinine,
      eGFR, UPCR, log10TKV (p > 0.05). CONCLUSION: There was no association of serum
      angiogenic growth factors with TKV or renal failure in ADPKD patients. Increased
      serum Ang-2 observed in stages 1-2 CKD suggests that angiogenesis plays a role in
      the progression of early stage ADPKD, but not at later stages of the disease.
      This may be explained by possible cessation of angiogenesis in advanced stages of
      CKD due to the increased number of sclerotic glomeruli.

PMID- 29654398
TI  - Long non-coding RNA taurine-upregulated gene 1 correlates with poor prognosis,
      induces cell proliferation, and represses cell apoptosis via targeting aurora
      kinase A in adult acute myeloid leukemia.
AB  - This study aimed to investigate the correlation of long non-coding RNA (lncRNA)
      taurine-upregulated gene 1 (TUG1) with clinicopathological feature and prognosis,
      and to explore its effect on cell proliferation and apoptosis as well as the
      relevant target genes in adult acute myeloid leukemia (AML). LncRNA TUG1
      expression was detected in bone marrow samples from 186 AML patients and 62
      controls. Blank mimic, lncRNA TUG1 mimic, blank inhibitor, and lncRNA TUG1
      inhibitor lentivirus vectors were transfected in KG-1 cells. Rescue experiment
      was performed by transfection of lncRNA TUG1 inhibitor and aurora kinase A
      (AURKA) mimic lentivirus vectors. Cell proliferation, apoptosis, RNA, and protein
      expressions were determined by CKK-8, annexin V-FITC-propidium iodide,
      quantitative polymerase chain reaction, and western blot assays. LncRNA TUG1
      expression was higher in AML patients compared to controls and correlated with
      higher white blood cell counts, monosomal karyotype, FLT3-ITD mutation, poor-risk
      stratification, and poor prognosis, which independently predicted worse event
      free survival and overall survival. In vitro, lncRNA TUG1 expression was higher
      in AML cell lines (KG-1, MOLM-14, HL-60, NB-4, and THP-1 cells) compared to
      controls. LncRNA TUG1 mimic promoted cell proliferation and decreased cell
      apoptosis rate, while lncRNA TUG1 inhibitor repressed cell proliferation and
      increased cell apoptosis rate. Rescue experiment showed that AURKA attenuated the
      influence of lncRNA TUG1 on AML cell proliferation and apoptosis. In conclusion,
      lncRNA TUG1 associates with advanced disease and worse prognosis in adult AML
      patients, and it induces AML cell proliferation and represses cell apoptosis via
      targeting AURKA.

PMID- 29654399
TI  - Characteristics of children admitted to intensive care with acute bronchiolitis.
AB  - : To assess factors associated with outcome in children admitted to paediatric
      intensive care (PIC) with bronchiolitis. A retrospective study of children
      admitted to the PICU at St Mary's Hospital, London with bronchiolitis over a 6
      year period (2011-2016). All bronchiolitis admissions < 2 years were included.
      Data collected particularly noted risk factors for severity, demographics,
      microbiology and outcome. We compared respiratory syncytial virus (RSV) with non
      RSV status. Multivariate analysis was performed. Two hundred seventy-four
      patients were identified. Median age was 60 days (IQR 28-150 days), 63% were
      male, 90% were invasively ventilated and 42% were previously healthy. Pre
      existing co-morbidities were present in 38%. The most frequently isolated
      pathogens were RSV (60%) and rhinovirus (26%). Co-infection was present in 45%,
      most commonly with RSV, rhinovirus and bacterial pathogens. Median length of stay
      (LOS) was 6 days (IQR 4.75-10). Younger age, prematurity, RSV, co-infection and
      co-morbidity were identified as significant risk factors for prolonged LOS. Six
      children died. Five of these had documented co-morbidities. CONCLUSION: RSV
      causes more severe bronchiolitis than other viruses. Nearly half of children
      admitted to PICU with RSV were previously healthy. Current guidelines for
      immunoprophylaxis of RSV bronchiolitis should be re-considered. What is Known: *
      Bronchiolitis is one of the most common reasons for unplanned PICU admission. The
      most common virus causing bronchiolitis is RSV * Bronchiolitis severe enough to
      require admission to PICU is associated with frequent morbidity but has low
      mortality. What is New: * RSV causes more severe bronchiolitis than other
      viruses. * Nearly half of all children admitted to PICU with RSV were previously
      healthy.

PMID- 29654401
TI  - Response to "Masturbation: Scientific Evidence and Islam's View".

PMID- 29654400
TI  - Development of a core set of quality indicators for paediatric primary care
      practices in Europe, COSI-PPC-EU.
AB  - : Paediatric ambulatory healthcare systems in Europe are, because of historical
      reasons, diverse and show strikingly different outcomes. All across Europe, the
      benchmarking of structures, processes and outcomes could reveal opportunities for
      improving Paediatric Primary Care (PPC). The aim of this study was to develop a
      set of Quality Indicators (QIs) to assess and monitor PPC in Europe. In a three
      step process, we used the available external evidence and European expert
      consensus in a modified RAND/UCLA Appropriateness Method (RAM) to develop an
      indicator set. (1) A broad literature and online research of published QI and
      guidelines yielded an inventory of 1516 QI. (2) A collaborative panel of
      paediatric senior experts from the European Academy of Paediatrics (EAP) and the
      European Confederation of Primary Care Paediatricians (ECPCP) from 15 European
      countries participated in a first consensus process to reduce the initial
      indicator inventory by eliminating not PPC-focused indicators and duplicates. (3)
      In a second consensus process, the panel rated the QI regarding validity and
      feasibility. The final QI set "COSI-PPC-EU" consists of 42 indicators in five
      categories of PPC: (A) health promotion/prevention/screening (13 QI), (B) acute
      care (9 QI), (C) chronic care (8 QI), (D) practice management (3 QI) and (E)
      patient safety (9 QI). CONCLUSION: COSI-PPC-EU represents a consented set of a
      limited number of valid quality indicators for the application in paediatric
      primary care in different healthcare systems throughout Europe. What is Known: *
      Paediatric ambulatory healthcare systems in Europe are diverse and show
      strikingly different outcomes. * There are known gaps in quality performance
      measures of paediatric primary care in Europe. Pre-existing sets of quality
      indicators are predominantly limited to national populations, specific diseases
      and hospital care. What is New: * A set of 42 quality indicators for primary
      paediatric care in Europe was developed in a multi-country collaborative effort.
      The method combined a systematic literature review and a consensus process among
      European paediatric experts. * The quality indicator set can facilitate quality
      improvement of PPC. After studying the feasibility, providers can use COSI-PPC-EU
      to monitor, compare and improve performance of practices, regions and countries.

PMID- 29654402
TI  - Decreasing Operating Room Turnover Time: A Resource Neutral Initiative.

PMID- 29654403
TI  - Antitumor activity of chitosan from mayfly with comparison to commercially
      available low, medium and high molecular weight chitosans.
AB  - Insects' cuticles have a potential to be evaluated as a chitin source. Especially
      adults of aquatic insects like mayflies (order Ephemeroptera) swarm in enormous
      numbers in artificially lit areas while mating in spring and then die by leaving
      huge amounts of dead insects' bodies. Here in this study, mayfly corpses were
      harvested and used for production of low MW chitosan. Dried mayfly bodies had
      10.21% chitin content; mayfly chitin was converted into chitosan with efficiency
      rate of 78.43% (deacetylation degree, 84.3%; MW, 3.69 kDa). Cytotoxicity and anti
      proliferative activity of mayfly and commercially available shrimp chitosans
      (low, medium, and high MW) were determined on L929 fibroblast and three different
      cancer types including HeLa, A549, and WiDr. Apoptosis and necrosis stimulating
      potential of mayfly and commercial chitosans were also evaluated on A549 and WiDr
      cells using acridine orange and propidium iodide dual staining to observe
      morphological changes in nuclei and thus to reveal the predominant cell death
      mechanism. The effects of chitosans have varied depending on cell types,
      concentration, and chitosan derivatives. Mayfly and low MW chitosans had a
      cytotoxic effect at a concentration of 500 MUg mL-1 on non-cancer cells. At
      concentrations below this value (250 MUg mL-1), mayfly and commercial chitosans
      except high MW one exhibited strong inhibitory activity on cancer cells
      especially A549 and WiDr cells. Mayfly chitosan induced early and late apoptosis
      in A549 cells, but late apoptosis and necrosis in WiDr cells. This study suggests
      that dead bodies of mayflies can be used for production of low MW chitosan with
      anti-proliferative activity.

PMID- 29654404
TI  - Asymmetrical intrapleural pressure distribution: a cause for scoliosis? A
      computational analysis.
AB  - PURPOSE: The mechanical link between the pleural physiology and the development
      of scoliosis is still unresolved. The intrapleural pressure (IPP) which is
      distributed across the inner chest wall has yet been widely neglected in etiology
      debates. With this study, we attempted to investigate the mechanical influence of
      the IPP distribution on the shape of the spinal curvature. METHODS: A finite
      element model of pleura, chest and spine was created based on CT data of a
      patient with no visual deformities. Different IPP distributions at a static end
      of expiration condition were investigated, such as the influence of an asymmetry
      in the IPP distribution between the left and right hemithorax. The results were
      then compared to clinical data. RESULTS: The application of the IPP resulted in a
      compressive force of 22.3 N and a flexion moment of 2.8 N m at S1. An
      asymmetrical pressure between the left and right hemithorax resulted in lateral
      deviation of the spine towards the side of the reduced negative pressure. In
      particular, the pressure within the dorsal section of the rib cage had a strong
      influence on the vertebral rotation, while the pressure in medial and ventral
      region affected the lateral displacement. CONCLUSIONS: An asymmetrical IPP caused
      spinal deformation patterns which were comparable to deformation patterns seen in
      scoliotic spines. The calculated reaction forces suggest that the IPP contributes
      in counterbalancing the weight of the intrathoracic organs. The study confirms
      the potential relevance of the IPP for spinal biomechanics and pathologies, such
      as adolescent idiopathic scoliosis.

PMID- 29654405
TI  - Elucidating early CT after pancreatico-duodenectomy: a primer for radiologists.
AB  - : Pancreatico-duodenectomy (PD) represents the standard surgical treatment for
      resectable malignancies of the pancreatic head, distal common bile duct,
      periampullary region and duodenum, and is also performed to manage selected
      benign tumours and refractory chronic pancreatitis. Despite improved surgical
      techniques and acceptable mortality, PD remains a technically demanding, high
      risk operation burdened with high morbidity (complication rates 40-50% of
      patients). Multidetector computed tomography (CT) represents the mainstay
      modality to rapidly investigate the postoperative abdomen, and to provide a
      consistent basis for an appropriate choice between conservative, interventional
      or surgical treatment. However, radiologists require familiarity with the
      surgically altered anatomy, awareness of expected imaging appearances and
      possible complications to correctly interpret early post-PD CT studies. This
      paper provides an overview of surgical indications and techniques, discusses risk
      factors and clinical manifestations of the usual postsurgical complications, and
      suggests appropriate techniques and indications for early postoperative CT
      imaging. Afterwards, the usual, normal early post-PD CT findings are presented,
      including transient fluid, pneumobilia, delayed gastric emptying, identification
      of pancreatic gland remnant and of surgical anastomoses. Finally, several imaging
      examples review the most common and some unusual complications such as pancreatic
      fistula, bile leaks, abscesses, intraluminal and extraluminal haemorrhage, and
      acute pancreatitis. TEACHING POINTS: * Pancreatico-duodenectomy (PD) is a
      technically demanding surgery burdened with high morbidity (40-50%). *
      Multidetector CT is the mainstay technique to investigate suspected complications
      following PD. * Interpreting post-PD CT requires knowledge of surgically altered
      anatomy and expected findings. * CT showing collection at surgical site supports
      clinico-biological diagnosis of pancreatic fistula. * Other complications include
      biliary leaks, haemorrhage, abscesses and venous thrombosis.

PMID- 29654406
TI  - Knee strength, power and stair performance of the elderly 5 years after
      unicompartmental knee arthroplasty.
AB  - BACKGROUND: Unicompartmental knee arthroplasty (UKA) has been shown to
      demonstrate some satisfactory short-term outcomes. However, to our knowledge,
      there have been no reports on midterm or long-term knee extensor strength and leg
      extensor power post-UKA. AIMS: Therefore, the purposes of this study were: (1) to
      assess the isokinetic knee extensor strength, leg extensor power and stair
      performance of elderly participants at 5 years UKA post-operation; (2) to compare
      the differences in knee extensor strength and leg extensor power between the UKA
      and contralateral healthy limbs. METHODS: Nineteen elderly participants (75 +/- 5
      years) who had a medial or a lateral compartment UKA at 5 years post-operation
      were recruited. The isokinetic knee extensor strength and leg extensor power were
      measured. The stair performance was tested on a 4-step stair, and ascent and
      descent velocities were calculated. The pain level was assessed. RESULTS: The UKA
      limbs' knee extensor strength and leg extensor power were 1.01 +/- 0.39 Nm/kg and
      0.98 +/- 0.27 W/kg, respectively. The stair ascent and descent velocities were
      0.37 +/- 0.07 and 0.38 +/- 0.11 m/s, respectively. In addition, the UKA limbs
      exhibited comparable knee strength and leg power relative to the contralateral
      limbs. DISCUSSION: In general, the knee extensor strength and leg extensor power
      exhibited by the UKA limbs at 5 years post-operation may be typical in comparison
      with the normative data. CONCLUSIONS: We suggest that UKA is a satisfactory
      treatment in regard to the recovery of knee strength, leg power and ability to
      climb up and down stairs.

PMID- 29654407
TI  - No difference in flexion power despite iliopsoas fatty degeneration in healed hip
      fractures with large lesser trochanter displacement.
AB  - OBJECTIVE: To evaluate iliopsoas atrophy and loss of function after displaced
      lesser trochanter fracture of the hip. DESIGN: Cohort study. SETTING: District
      hospital. PATIENTS: Twenty consecutive patients with pertrochanteric fracture and
      displacement of the lesser trochanter of > 20 mm. INTERVENTION: Fracture fixation
      with either an intramedullary nail or a plate. OUTCOME MEASUREMENTS: Clinical
      scores (Harris hip, WOMAC), hip flexion strength measurements, and magnetic
      resonance imaging findings. RESULTS: Compared with the contralateral non-operated
      side, the affected side showed no difference in hip flexion force in the supine
      upright neutral position and at 30 degrees  of flexion (205.4 N vs 221.7 N and
      178.9 N vs. 192.1 N at 0 degrees  and 30 degrees  flexion, respectively).
      However, the affected side showed a significantly greater degree of fatty
      infiltration compared with the contralateral side (global fatty degeneration
      index 1.085 vs 0.784), predominantly within the psoas and iliacus muscles.
      CONCLUSION: Severe displacement of the lesser trochanter (> 20 mm) in
      pertrochanteric fractures did not reduce hip flexion strength compared with the
      contralateral side. Displacement of the lesser trochanter in such cases can lead
      to fatty infiltration of the iliopsoas muscle unit. The amount of displacement of
      the lesser trochanter did not affect the degree of fatty infiltration. LEVEL OF
      EVIDENCE: II.

PMID- 29654409
TI  - Supraorbital approach through eyebrow skin incision for aneurysm clipping: how I
      do it.
AB  - BACKGROUND: Surgery has been in a huge development where the aim is to achieve
      same or better results with less complication in a less invasive way; these
      minimal approaches can be applied in a very safe way to aneurysmal neurosurgery.
      METHOD: Images are studied to optimize the patient positioning and the surgical
      roadmap. After the positioning, the skin incision, craniotomy, and dura incision
      are performed and intradural lesion is reached. A watertight closure is performed
      under the microscope. CONCLUSION: The keyhole approach requires some adaption
      from the side of the surgeon and can be performed only in cases envisioned to
      have no increased risk for the patient.

PMID- 29654408
TI  - Contemporary critical limb ischemia: Asian multidisciplinary consensus statement
      on the collaboration between endovascular therapy and wound care.
AB  - The burden of peripheral artery disease (PAD) and diabetes in Asia is projected
      to increase. Asia also has the highest incidence and prevalence of end-stage
      renal disease (ESRD) in the world. Therefore, most Asian patients with PAD might
      have diabetic PAD or ESRD-related PAD. Given these pandemic conditions, critical
      limb ischemia (CLI) with diabetes or ESRD, the most advanced and challenging
      subset of PAD, is an emerging public health issue in Asian countries. Given that
      diabetic and ESRD-related CLI have complex pathophysiology that involve arterial
      insufficiency, bacterial infection, neuropathy, and foot deformity, a coordinated
      approach that involves endovascular therapy and wound care is vital. Recently,
      there is increasing interaction among cardiologists, vascular surgeons,
      radiologists, orthopedic surgeons, and plastic surgeons beyond specialty and
      country boundaries in Asia. This article is intended to share practical Asian
      multidisciplinary consensus statement on the collaboration between endovascular
      therapy and wound care for CLI.

PMID- 29654410
TI  - Reactive oxygen species generation in aqueous solutions containing GdVO4:Eu3+
      nanoparticles and their complexes with methylene blue.
AB  - It this letter, we report the study of free radicals and reactive oxygen species
      (ROS) generation in water solutions containing gadolinium orthovanadate
      GdVO4:Eu3+ nanoparticles (VNPs) and their complexes with methylene blue (MB)
      photosensitizer. The catalytic activity was studied under UV-Vis and X-ray
      irradiation by three methods (conjugated dienes test, OH. radical, and singlet
      oxygen detection). It has been shown that the VNPs-MB complexes reveal high
      efficiency of ROS generation under UV-Vis irradiation associated with both high
      efficiency of OH. radicals generation by VNPs and singlet oxygen generation by MB
      due to nonradiative excitation energy transfer from VNPs to MB molecules.
      Contrary to that under X-ray irradiation, the strong OH . radicals scavenging by
      VNPs has been observed.

PMID- 29654411
TI  - Ciprofloxacin-lidocaine-based hydrogel: development, characterization, and in
      vivo evaluation in a second-degree burn model.
AB  - The purpose of this work was to develop an effective carbomer hydrogel to be used
      to treat second-degree burns that combined ciprofloxacin and lidocaine (CbCipLid
      hydrogel). Its antibiotic and anesthetic efficacy and the physical and chemical
      properties of the CbCipLid hydrogel (release rate and kinetics, rheology,
      appearance, and drug content) were evaluated both before and after a
      sterilization cycle and also after 6 months of storage. For the in vivo studies,
      second-degree burns were developed in a rat model. Animals were divided into
      three groups: CbCipLid hydrogel, silver sulfadiazine cream (reference), and
      carbomer hydrogel (as control). The treatments were applied daily for 21 days,
      and the healing was monitored by macroscopic observation and histologic
      evaluation. The anesthetic effect was evaluated through the corneal touch
      threshold in a rabbit eye model. The CbCipLid hydrogel obtained is transparent
      and allows the loading of ciprofloxacin above its solubility at a neutral pH,
      with a rheology which is convenient for topical administration. Its physical and
      chemical properties remained unchanged after sterilization and for at least six
      additional months. Both ciprofloxacin and lidocaine are reversibly released from
      the CbCipLid hydrogel with a kinetics fitting the Higuchi model. The presence of
      a biologic-like fluid increased the rate of drug delivery through an ionic
      exchange mechanism. Treatment with the CbCipLid hydrogel decreased the wound
      healing period, compared with the reference, and was associated with a greater
      number of fibroblasts and a faster rate of epithelialization and dermis
      reconstruction. These differences were assigned to the moist environment provided
      by the hydrogel and also to the presence of a therapeutic concentration of
      ciprofloxacin. Moreover, CbCipLid hydrogel provides an immediate anesthetic
      effect, which is significantly more intense than that of the reference. Based on
      these results, it is believed that the CbCipLid hydrogel could be a potential
      candidate in the prophylaxis/treatment of second-degree burns.

PMID- 29654412
TI  - The association of serum C-reactive protein with the occurrence and course of
      postpartum depression.
AB  - CRP has been positively correlated with depressive symptomatology but this has
      received less study in postpartum depression (PPD). In this secondary analysis of
      a trial of PPD treatment, depressive symptoms (Structured Interview Guide for the
      Hamilton Depression Rating Scale-Atypical Depression Symptoms (SIGH-ADS29)) and
      serum CRP levels were assessed and associations between CRP and SIGH-ADS29 scores
      evaluated. The associations between baseline log CRP and depression response and
      remission were also assessed. Of the 35 women included, neither baseline log CRP
      nor exit log CRP was significantly associated with SIGH-ADS29 score. Baseline CRP
      was not associated with response or remission. In this sample of women with PPD,
      CRP was not associated with depressive symptoms nor response to treatment.

PMID- 29654413
TI  - Latent trajectory groups of perinatal depressive and anxiety symptoms from
      pregnancy to early postpartum and their antenatal risk factors.
AB  - The aim of this study is to identify subgroups of women who exhibit distinct
      trajectory patterns of depressive and anxiety disorders from pregnancy to early
      postpartum and the risk factors associated with the latent trajectory group
      memberships. Women (n = 615) from the Feelings in Pregnancy and Motherhood (FIP)
      longitudinal study were followed from early pregnancy to early postpartum for a 7
      month period in 2006-2007. The semi-parametric group-based trajectory modeling
      approach was used to identify the latent trajectory groups. Multinomial logit
      models were then used to explore the association between latent trajectory group
      membership and antenatal characteristics. We identified four latent trajectory
      groups of perinatal depressive symptoms: "low-stable" (49.6%), "moderate-stable"
      (42.3%), "postpartum" (3.6%), and "antepartum" (4.6%). Significant risk factors
      associated with these trajectory group memberships were past depression, stress
      level, ethnicity, the mother's age, and relationship satisfaction. Three latent
      trajectory groups of perinatal anxiety symptoms were identified: "very low
      stable" (8.9%); "low-stable" (60.7%); and "moderate-stable" (30.4%). Significant
      risk factor associated with these trajectories were past depression, stress
      level, and income level. Latent trajectory groups of perinatal depressive and
      anxiety symptoms were identified to uncover potential heterogeneity in
      populations. Our findings support the need for multiple assessments starting from
      early pregnancy to the postpartum, which can give some important insights on the
      characteristics of the women at high symptom burden trajectories for early
      interventions that may alter the progress of their mental symptoms.

PMID- 29654414
TI  - Determination of the Genetic and Synergistic Suppression of a Methoxyfenozide
      Resistant Strain of the House Fly Musca domestica L. (Diptera: Muscidae).
AB  - Musca domestica Linnaeus (house fly, Diptera: Muscidae) is a major veterinary and
      medical important pest all over the world. These flies have ability to develop
      resistance to insecticides. The present trial was performed to discover the
      inheritance mode (autosomal, dominance, number of genes involved) and preliminary
      mechanism of methoxyfenozide resistance in order to provide basic information
      necessary to develop resistance management strategy for this pest. A strain of M.
      domestica (MXY-SEL) was exposed to methoxyfenozide for 44 generations which
      developed a 5253.90-fold level of resistance to methoxyfenozide. The overlapping
      fiducial limits of LC50 values of the reciprocal crosses, F1 (MXY-SEL ? *
      Susceptible ?) and F1? (MXY-SEL ? * Susceptible ?), suggest that inheritance of
      methoxyfenozide resistance was an autosomal and likely completely dominant trait
      (DLC = 0.93 and 0.94 for F1 and F1?, respectively). Backcrosses of the F1 with
      the parental MXY-SEL or Susceptible population predict a polygenic mode of
      inheritance. Piperonyl butoxide significantly altered the LC50 values, suggesting
      enhanced detoxification by cytochrome P450-dependent monooxygenases is a major
      mechanism of resistance to methoxyfenozide in the MXY-SEL strain. The estimated
      realized heritability was 0.07 for methoxyfenozide. These results would be
      helpful for the better management of M. domestica.

PMID- 29654415
TI  - Health-related quality of life of postmenopausal women with hormone receptor
      positive, human epidermal growth factor receptor 2-negative advanced breast
      cancer treated with ribociclib + letrozole: results from MONALEESA-2.
AB  - PURPOSE: Evaluate patient-reported outcomes (PROs) for postmenopausal women with
      hormone receptor-positive (HR+), human epidermal growth factor receptor 2
      negative (HER2-) advanced breast cancer treated with first-line ribociclib plus
      letrozole. METHODS: In the phase III MONALEESA-2 study (NCT01958021), 668
      patients were randomized 1:1 to ribociclib (600 mg/day; 3-weeks-on/1-week-off)
      plus letrozole (2.5 mg/day) or placebo plus letrozole. PROs were assessed using
      the European Organisation for Research and Treatment of Cancer core quality-of
      life (EORTC QLQ-C30) and breast cancer-specific (EORTC QLQ-BR23) questionnaires.
      Changes from baseline and time to deterioration in health-related quality of life
      (HRQoL) were analyzed using linear mixed-effect and stratified Cox regression
      models, respectively. Exploratory analysis of area-under-the-curve for change
      from baseline in pain score (AUC-pain) was performed. RESULTS: On-treatment HRQoL
      scores were consistently maintained from baseline and were similar between arms.
      A clinically meaningful (> 5 points) reduction in pain score was observed as
      early as Week 8 and was maintained up to Cycle 15 in the ribociclib arm. A
      statistically significant increase in mean AUC-pain was also observed in the
      ribociclib arm. Scores for all other EORTC QLQ-C30 and EORTC QLQ-BR23 domains
      were maintained from baseline and were similar between arms. CONCLUSIONS: HRQoL
      was consistently maintained from baseline in postmenopausal women with HR+, HER2-
      advanced breast cancer receiving ribociclib plus letrozole and was similar to
      that observed in the placebo plus letrozole arm. Together with the improved
      clinical efficacy and manageable safety profile, these PRO results provide
      additional support for the benefit of ribociclib plus letrozole in this patient
      population.

PMID- 29654416
TI  - Effects of physical exercise after treatment of early breast cancer: systematic
      review and meta-analysis.
AB  - PURPOSE: Randomized clinical trials are inconclusive regarding the role of
      physical exercise in anthropometric measurements, quality of life, and survival
      in breast cancer patients. Our aim was to conduct a systematic review and meta
      analysis to assess the effects of physical exercise on these outcomes in women
      who went through curative treatment of early-stage breast cancer. METHODS:
      Pubmed, Embase, Cochrane Library were searched for randomized clinical trial
      comparing physical exercise (counseling or structured programs with
      supervised/individualized exercise sessions) with usual care in women that went
      through for breast cancer treatment. Primary outcomes were overall survival and
      disease-free survival, while secondary outcomes were weight loss, body mass
      index, waist-hip ratio, percentage of body fat, and quality of life. RESULTS: We
      found 60 randomized clinical trials, only one of them showed mortality data; the
      HR for mortality was 0.45 (95% CI 0.21-0.97) for the intervention group when
      compared to the control group. Physical exercise was associated with weight
      reduction (- 1.36 kg, 95% CI - 2.51 to - 0.21, p = 0.02), lower body mass index (
      0.89 kg/m2, 95% CI - 1.50 to - 0.28, p < 0.01), and lower percentage of body fat
      (- 1.60 percentage points, 95% CI - 2.31 to - 0.88, p < 0.01). There was an
      increase in the quality of life (standardized mean difference of 0.45, 95% CI
      0.20-0.69, p < 0.01). CONCLUSIONS: The articles found had heterogeneous types of
      intervention, but they showed significant effects on anthropometric measures and
      quality of life. Among them, only one study had mortality as outcome and it
      showed physical exercise as a protective intervention. Despite these findings,
      publication bias and poor methodological quality were presented. Physical
      exercise should be advised for breast cancer survivors since it has no adverse
      effects and can improve anthropometrics measures and quality of life. PROSPERO
      registry: CRD42014008743.

PMID- 29654417
TI  - Healthcare Text Classification System and its Performance Evaluation: A Source of
      Better Intelligence by Characterizing Healthcare Text.
AB  - A machine learning (ML)-based text classification system has several classifiers.
      The performance evaluation (PE) of the ML system is typically driven by the
      training data size and the partition protocols used. Such systems lead to low
      accuracy because the text classification systems lack the ability to model the
      input text data in terms of noise characteristics. This research study proposes a
      concept of misrepresentation ratio (MRR) on input healthcare text data and models
      the PE criteria for validating the hypothesis. Further, such a novel system
      provides a platform to amalgamate several attributes of the ML system such as:
      data size, classifier type, partitioning protocol and percentage MRR. Our
      comprehensive data analysis consisted of five types of text data sets (TwitterA,
      WebKB4, Disease, Reuters (R8), and SMS); five kinds of classifiers (support
      vector machine with linear kernel (SVM-L), MLP-based neural network, AdaBoost,
      stochastic gradient descent and decision tree); and five types of training
      protocols (K2, K4, K5, K10 and JK). Using the decreasing order of MRR, our ML
      system demonstrates the mean classification accuracies as: 70.13 +/- 0.15%, 87.34
      +/- 0.06%, 93.73 +/- 0.03%, 94.45 +/- 0.03% and 97.83 +/- 0.01%, respectively,
      using all the classifiers and protocols. The corresponding AUC is 0.98 for SMS
      data using Multi-Layer Perceptron (MLP) based neural network. All the
      classifiers, the best accuracy of 91.84 +/- 0.04% is shown to be of MLP-based
      neural network and this is 6% better over previously published. Further we
      observed that as MRR decreases, the system robustness increases and validated by
      standard deviations. The overall text system accuracy using all data types,
      classifiers, protocols is 89%, thereby showing the entire ML system to be novel,
      robust and unique. The system is also tested for stability and reliability.

PMID- 29654418
TI  - Interictal levels of calcitonin gene related peptide in gingival crevicular fluid
      of chronic migraine patients.
AB  - Calcitonin gene related peptide (CGRP) is a mediator of neurogenic inflammation
      playing a major role in the pathogenesis of migraine. Increases in serum CGRP
      have been detected previously in migraineurs and a return to baseline values
      regarded as successful treatment. As gingival crevicular fluid is known to
      originate from the serum, the aim of this study is to measure the CGRP content of
      gingival crevicular fluid (GCF) in chronic migraine patients and to determine
      whether there is a correlation between serum and GCF values of CGRP. For this
      study, 24 female individuals suffering from chronic migraine with aura were age
      matched with 15 healthy individuals. Serum and GCF samples were obtained from
      both groups and enzyme linked immunosorbent assay performed to measure CGRP
      concentration. The level of CGRP in the serum and GCF of chronic migraine
      patients was 41 +/- 16 pg/mL and 0.25 +/- 0.09 pg/MUg respectively while in
      healthy individuals CGRP levels were 29 +/- 8 pg/mL and 0.19 +/- 0.07 pg/MUg. The
      correlation between CGRP levels of the GCF and serum was 0.88 for migraineurs and
      0.81 in the controls. Only a weak positive relationship was observed between age
      and CGRP levels in both groups. CGRP levels were higher in migraineurs compared
      with controls both in serum and GCF. Furthermore there is a strong correlation
      between CGRP levels of the serum and GCF. The results of this study suggest that
      CGRP levels of GCF have potential diagnostic purposes in patients with chronic
      migraine.

PMID- 29654419
TI  - Bilateral vestibular impairment in Vogt Koyanagi Harada syndrome: a case report.

PMID- 29654420
TI  - Comparison of gingival depigmentation with Er,Cr:YSGG laser and surgical
      stripping, a 12-month follow-up.
AB  - Gingival melanin hyperpigmentation is an esthetic concern for many individuals.
      In this study, we compared the standard surgical removal method with two
      different Er,Cr:YSGG laser settings in order to find the best treatment method.
      In 33 dental arches, the following three treatment groups were comparatively
      evaluated: (1) surgical stripping, (2) removal with laser setting 1 (4.5 W, 50
      Hz, 100% water, 80% air, 60 MUs, 800 MUm Tip; MZ8), and (3) laser setting 2 (2.5
      W, 50 Hz, 20% water, 40% air, 700 MUs, 800 MUm Tip; MZ8). We comparatively
      evaluated pain, patient satisfaction and wound healing, treatment time, and the
      amount of bleeding. Re-pigmentation was evaluated after 1 and 12 months by Hedin
      and Dummet pigmentation scores. Laser setting 1 had the best results regarding
      pain and patient satisfaction, although not statistically significant (P > 0.05).
      Wound healing results were better using lasers compared to surgical stripping (P
      < 0.05). Laser setting 1 was a faster procedure with mild amounts of bleeding.
      The least amount of bleeding was seen with laser setting 2. After 1 month, only
      two cases of the laser setting 2-treated areas showed an isolated pigmented area
      in the papilla; at 12 months, the mean Hedin indexes were still less than 2 and
      mean Dummett index less than 1 in all treatment techniques, with the lowest
      scores seen in the laser setting 1 sites. Based on our results, Er,Cr:YSGG laser
      can be more convenient for gingival depigmentation compared to surgical blade.
      Although not statistically significant, laser setting 1 with shorter pulse
      duration and higher water spray showed better overall results. However, laser
      setting 2, with longer pulse duration and less water spray, resulted in better
      coagulative effects and can be used to control bleeding wherever necessary in
      clinical practice.

PMID- 29654421
TI  - Comparative microstructural analysis of bone osteotomies after cutting by
      computer-assisted robot-guided laser osteotome and piezoelectric osteotome: an in
      vivo animal study.
AB  - Most industrial laser applications utilize computer and robot assistance, for
      guidance, safety, repeatability, and precision. In contrast, medical applications
      using laser systems are mostly conducted manually. The advantages can be
      effective only when the system is coupled to a robotic guidance, as operating by
      hand does not reach the required accuracy. We currently developed the first laser
      osteotome which offers preoperative planning based on CT data, robot guidance,
      and a precise execution of the laser cuts. In an animal trial, our system was
      used to create a grid pattern of the same depth on the inner layer of parietal
      bone in 12 adult sheep. The same bone cuts were done with piezoelectric osteotome
      on the contralateral side. The micro-CT and histological analysis showed more new
      mineralized bone in the laser group compared to the piezoelectric group. As well,
      a cutting pattern with especially a constant osteotomy depth in the laser group
      was demonstrated. The here presented autonomous osteotomy tool shows not only an
      advantage in early bone healing stage but additionally sharp bone cuts with a
      very high accuracy and freely selectable design cuts.

PMID- 29654422
TI  - Removal of unwanted hair: efficacy, tolerability, and safety of long-pulsed 755
      nm alexandrite laser equipped with a sapphire handpiece.
AB  - Due to the difference in refraction coefficients between air and the corneal
      epithelium, irradiation of the skin with a light source can lead to reflection of
      the energy and its leakage to the skin causes epidermal injury. All of which
      decreases the efficacy of treatment. We evaluated cooling sapphire handpieces'
      efficacy in decreasing pain and epidermal injuries and enhancing the treatment
      outcome in laser hair removal. A total of 49 patients with Fitzpatrick skin types
      of II to IV were treated for laser hair removal on face, limbs, inguinal, and
      axillary areas with pulsed 755-nm alexandrite laser equipped with a sapphire
      handpiece and the cooling system. Hair counts were performed by two independent
      observers at the baseline and 3 months after the final treatment. A marked
      reduction in hair regrowth was noted 3 months after the final treatment in all
      body locations studied. Clinical hair reduction was observed and fully assessed.
      There were no serious side effects with an average pain score of 4.6 out of 40.
      The cooled sapphire cylinder tip has been shown to minimize epidermal injury and
      reduce the system energy leaks to the skin.

PMID- 29654423
TI  - Adoption and Design of Emerging Dietary Policies to Improve Cardiometabolic
      Health in the US.
AB  - PURPOSE OF REVIEW: Suboptimal diet is a leading cause of cardiometabolic disease
      and economic burdens. Evidence-based dietary policies within 5 domains-food
      prices, reformulation, marketing, labeling, and government food assistance
      programs-appear promising at improving cardiometabolic health. Yet, the extent of
      new dietary policy adoption in the US and key elements crucial to define in
      designing such policies are not well established. We created an inventory of
      recent US dietary policy cases aiming to improve cardiometabolic health and
      assessed the extent of their proposal and adoption at federal, state, local, and
      tribal levels; and categorized and characterized the key elements in their policy
      design. RECENT FINDINGS: Recent federal dietary policies adopted to improve
      cardiometabolic health include reformulation (trans-fat elimination), marketing
      (mass-media campaigns to increase fruits and vegetables), labeling (Nutrition
      Facts Panel updates, menu calorie labeling), and food assistance programs
      (financial incentives for fruits and vegetables in the Supplemental Nutrition
      Assistance Program (SNAP) and Women, Infant and Children (WIC) program). Federal
      voluntary guidelines have been proposed for sodium reformulation and food
      marketing to children. Recent state proposals included sugar-sweetened beverage
      (SSB) taxes, marketing restrictions, and SNAP restrictions, but few were enacted.
      Local efforts varied significantly, with certain localities consistently leading
      in the proposal or adoption of relevant policies. Across all jurisdictions, most
      commonly selected dietary targets included fruits and vegetables, SSBs, trans
      fat, added sugar, sodium, and calories; other healthy (e.g., nuts) or unhealthy
      (e.g., processed meats) factors were largely not addressed. Key policy elements
      to define in designing these policies included those common across domains (e.g.,
      level of government, target population, dietary target, dietary definition,
      implementation mechanism), and domain-specific (e.g., media channels for food
      marketing domain) or policy-specific (e.g., earmarking for taxes) elements.
      Characteristics of certain elements were similarly defined (e.g., fruit and
      vegetable definition, warning language used in SSB warning labels), while others
      varied across cases within a policy (e.g., tax base for SSB taxes). Several key
      elements were not always sufficiently characterized in government documents, and
      dietary target selections and definitions did not consistently align with the
      evidence-base. These findings highlight recent action on dietary policies to
      improve cardiometabolic health in the US; and key elements necessary to design
      such policies.

PMID- 29654424
TI  - Deformable Registration for Longitudinal Breast MRI Screening.
AB  - MRI screening of high-risk patients for breast cancer provides very high
      sensitivity, but with a high recall rate and negative biopsies. Comparing the
      current exam to prior exams reduces the number of follow-up procedures requested
      by radiologists. Such comparison, however, can be challenging due to the highly
      deformable nature of breast tissues. Automated co-registration of multiple scans
      has the potential to aid diagnosis by providing 3D images for side-by-side
      comparison and also for use in CAD systems. Although many deformable registration
      techniques exist, they generally have a large number of parameters that need to
      be optimized and validated for each new application. Here, we propose a framework
      for such optimization and also identify the optimal input parameter set for
      registration of 3D T1-weighted MRI of breast using Elastix, a widely used and
      freely available registration tool. A numerical simulation study was first
      conducted to model the breast tissue and its deformation through finite element
      (FE) modeling. This model generated the ground truth for evaluating the
      registration accuracy by providing the deformation of each voxel in the breast
      volume. An exhaustive search was performed over various values of 7 registration
      parameters (4050 different combinations of parameters were assessed) and the
      optimum parameter set was determined. This study showed that there was a large
      variation in the registration accuracy of different parameter sets ranging from
      0.29 mm to 2.50 mm in median registration error and 3.71 mm to 8.90 mm in 95
      percentile of the registration error. Mean registration errors of 0.32 mm, 0.29
      mm, and 0.30 mm and 95 percentile errors of 3.71 mm, 5.02 mm, and 4.70 mm were
      obtained by the three best parameter sets. The optimal parameter set was applied
      to consecutive breast MRI scans of 13 patients. A radiologist identified 113
      landmark pairs (~ 11 per patient) which were used to assess registration
      accuracy. The results demonstrated that using the optimal registration parameter
      set, a registration accuracy (in mm) of 3.4 [1.8 6.8] was achieved.

PMID- 29654425
TI  - An Automatic and Robust Decision Support System for Accurate Acute Leukemia
      Diagnosis from Blood Microscopic Images.
AB  - This paper proposes an automatic and robust decision support system for accurate
      acute leukemia diagnosis from blood microscopic images. It is a challenging issue
      to segment leukocytes under uneven imaging conditions since features of
      microscopic leukocyte images change in different laboratories. Therefore, this
      paper introduces an automatic robust method to segment leukocyte from blood
      microscopic images. The proposed robust segmentation technique was designed based
      on the fact that if background and erythrocytes could be removed from the blood
      microscopic image, the remainder area will indicate leukocyte candidate regions.
      A new set of features based on hematologist visual criteria for the recognition
      of malignant leukocytes in blood samples comprising shape, color, and LBP-based
      texture features are extracted. Two new ensemble classifiers are proposed for
      healthy and malignant leukocytes classification which each of them is highly
      effective in different levels of analysis. Experimental results demonstrate that
      the proposed approach effectively segments leukocytes from various types of blood
      microscopic images. The proposed method performs better than other available
      methods in terms of robustness and accuracy. The final accuracy rate achieved by
      the proposed method is 98.10% in cell level. To the best of our knowledge, the
      image level test for acute lymphoblastic leukemia (ALL) recognition was performed
      on the proposed system for the first time that achieves the best accuracy rate of
      89.81%.

PMID- 29654426
TI  - Direct visualization of single virus restoration after damage in real time.
AB  - We use the nano-dissection capabilities of atomic force microscopy to induce
      structural alterations on individual virus capsids in liquid milieu. We fracture
      the protein shells either with single nanoindentations or by increasing the tip
      sample interaction force in amplitude modulation dynamic mode. The normal
      behavior is that these cracks persist in time. However, in very rare occasions
      they self-recuperate to retrieve apparently unaltered virus particles. In this
      work, we show the topographical evolution of three of these exceptional events
      occurring in T7 bacteriophage capsids. Our data show that single nanoindentation
      produces a local recoverable fracture that corresponds to the deepening of a
      capsomer. In contrast, imaging in dynamic mode induced cracks that separate the
      virus morphological subunits. In both cases, the breakage patterns follow
      intratrimeric loci.

PMID- 29654427
TI  - Sociodemographic disparities in the occurrence of medical conditions among
      adolescent and young adult Hodgkin lymphoma survivors.
AB  - PURPOSE: Hodgkin lymphoma (HL) survivors experience high risks of second cancers
      and cardiovascular disease, but no studies have considered whether the occurrence
      of these and other medical conditions differ by sociodemographic factors in
      adolescent and young adult (AYA) survivors. METHODS: Data for 5,085 patients aged
      15-39 when diagnosed with HL during 1996-2012 and surviving >= 2 years were
      obtained from the California Cancer Registry and linked to hospitalization data.
      We examined the impact of race/ethnicity, neighborhood socioeconomic status
      (SES), and health insurance on the occurrence of medical conditions (>= 2 years
      after diagnosis) and the impact of medical conditions on survival using
      multivariable Cox proportional hazards regression. RESULTS: Twenty-six percent of
      AYAs experienced at least one medical condition and 15% had >= 2 medical
      conditions after treatment for HL. In multivariable analyses, Black HL survivors
      had a higher likelihood (vs. non-Hispanic Whites) of endocrine [hazard ratio (HR)
      = 1.37, 95% confidence interval (CI) 1.05-1.78] and circulatory system diseases
      (HR = 1.58, CI 1.17-2.14); Hispanics had a higher likelihood of endocrine
      diseases [HR = 1.24 (1.04-1.48)]. AYAs with public or no insurance (vs.
      private/military) had higher likelihood of circulatory system diseases,
      respiratory system diseases, chronic kidney disease/renal failure, liver disease,
      and endocrine diseases. AYAs residing in low SES neighborhoods (vs. high) had
      higher likelihood of respiratory system and endocrine diseases. AYAs with these
      medical conditions or second cancers had an over twofold increased risk of death.
      CONCLUSION: Strategies to improve health care utilization for surveillance and
      secondary prevention among AYA HL survivors at increased risk of medical
      conditions may improve outcomes.

PMID- 29654428
TI  - Treatment outcomes of patients with spinal metastases derived from hepatocellular
      carcinoma.
AB  - BACKGROUND: The prognosis of hepatocellular carcinoma (HCC) used to be poor, but
      it has recently improved, which has meant that clinicians have greater
      opportunity to treat spinal metastases and the associated epidural spinal cord
      compression. However, there have been few systematic functional studies about HCC
      derived spinal metastases. The treatment outcomes of surgical treatment for HCC
      derived metastatic spinal tumors were investigated. METHODS: The post-treatment
      survival period and pain, paralysis, and disturbance of activities of daily
      living (ADL) were investigated in 60 patients (surgery 25, conservative treatment
      35). RESULTS: The mean post-treatment survival period was 7.4 +/- 8.2 months
      (range 0.3-36 months). Univariate analysis indicated that the following factors
      influenced survival: the patient's general condition, presence/absence of major
      internal organ metastasis, serum albumin level, Child-Pugh classification,
      surgical treatment for spinal metastasis, and bone-modifying agent treatment. In
      the multivariate analysis of these 6 items, 3 significant factors were extracted:
      the patient's general condition, the serum albumin level, and bone-modifying
      agent treatment. Pain significantly improved in both groups (p < 0.001).
      Paralysis did not change significantly in the surgical group (p = 0.575), but it
      was significantly aggravated in the conservative treatment group (p = 0.047). The
      ADL abilities of the surgical group improved significantly (p < 0.001).
      CONCLUSION: Most patients exhibited poor survival. In the conservative treatment
      group, paralysis was significantly aggravated, and little improvement was seen in
      the patients' ADL abilities. In the surgical group, the patients' ADL abilities
      improved significantly, but their paralysis did not. Therefore, surgery should be
      actively performed for HCC-derived spinal metastasis whenever it is indicated.

PMID- 29654429
TI  - Minimally Invasive Techniques for Bladder Reconstruction.
AB  - PURPOSE OF REVIEW: Bladder reconstruction surgery is a key component of
      neurogenic lower urinary tract dysfunction (nLUTD) management. Traditionally,
      given the complexity and unpredictable operative challenges of bladder
      reconstruction in this patient population, little consideration has been given to
      performing lower urinary tract reconstruction in a minimally invasive approach.
      RECENT FINDINGS: We describe the innovative minimally invasive surgical
      techniques in four major categories of reconstructive procedures for nLUTD: (A)
      ileal bladder augmentation, the use of a low morbidity open Pfannenstiel incision
      and the use of laparoscopy and robotics; (B) creation of a catheterizable
      channel, the use of laparoscopy and robotics for Mitrofanoff procedures; (C)
      creation of both a bladder augmentation and catheterizable channel, the use of a
      hand-assisted approach for the creation of a continent cutaneous ileocystoplasty;
      and (D) bladder neck artificial urinary sphincter implantation: the use of a
      robotics. Patients with nLUTD need surgical solutions that can improve their
      quality of life over several decades. As experience with robotics increases and
      as technology provides us with new tools to ease minimally invasive bladder
      reconstruction, we can expect that the field will continue to grow and improve.

PMID- 29654430
TI  - Protective Effects of Isoliquiritigenin on LPS-Induced Acute Lung Injury by
      Activating PPAR-gamma.
AB  - Isoliquiritigenin (ILG), a major ingredient of licorice, has been reported to
      have anti-oxidative and anti-inflammatory effects. The aim of this study was to
      investigate the protective effects of ILG on lung injury using an animal model of
      lipopolysaccharide (LPS)-induced acute lung injury (ALI). Male BALB/c mice were
      conditioned with ILG 1 h before intranasal instillation of LPS. The effects of
      ILG on lung injury were assessed by measuring lung histopathological examination,
      MPO assay, wet/dry (W/D) ratio, and inflammatory cytokine production. The results
      showed that ILG significantly inhibited LPS-induced lung histopathological
      changes and the MPO activity. Meanwhile, it attenuated the wet/dry (W/D) ratio in
      the lung tissues. The results also indicated that ILG inhibited LPS-induced ALI
      in the expression of inflammatory cytokines in the BALF. Furthermore, ILG can
      decrease the activity of NF-kappaB and can increase the expression of PPAR-gamma.
      These findings suggested that ILG inhibited the inflammatory of LPS-induced lung
      injury by activating PPAR-gamma and inhibiting NF-kappaB activation.

PMID- 29654431
TI  - Saikosaponin a Inhibits Cigarette Smoke-Induced Oxidant Stress and Inflammatory
      Responses by Activation of Nrf2.
AB  - Saikosaponin a (SSa), a triterpenoid saponin, has numerous pharmacological
      properties, including anti-inflammatory and antioxidant effects. The purpose of
      this study was to investigate whether and how SSa protected against cigarette
      smoke (CS)-induced lung inflammation in mice. The mice were exposed to CS and SSa
      was administered by an intraperitoneal (i.p.) injection 1 h before CS treatment
      for 5 consecutive days. The results showed that SSa significantly inhibited CS
      induced inflammatory cell infiltration, NO, TNF-alpha, and IL-1beta production in
      BALF. SSa also inhibited CS-induced MPO and MDA contents in lung tissues.
      Furthermore, SSa significantly inhibited CS-induced NF-kappaB and upregulated the
      expression of Nrf2 and HO-1. In conclusion, these results support a therapeutic
      potential for SSa in CS-induced lung inflammation.

PMID- 29654432
TI  - Salicytamide: a New Anti-inflammatory Designed Drug Candidate.
AB  - Salicytamide is a new drug developed through molecular modelling and rational
      drug design by the molecular association of paracetamol and salicylic acid. This
      study was conducted to assess the acute oral toxicity, antinociceptive, and
      antioedematogenic properties of salicytamide. Acute toxicity was based on the
      OECD 423 guidelines. Antinociceptive properties were investigated using the
      writhing, hot plate and formalin tests in Swiss mice. Antioedematogenic
      properties were evaluated using the carrageenan-induced paw oedema model and
      croton oil-induced dermatitis in Wistar rats. Salicytamide did not promote
      behavioural changes or animal deaths during acute oral toxicity evaluation.
      Furthermore, salicytamide exhibited peripheral antinociceptive activity as
      evidenced by the reduction in writhing behaviour (ED50 = 4.95 mg/kg) and licking
      time in the formalin test's inflammatory phase. Also, salicytamide elicited
      central antinociceptive activity on both hot plate test and formalin test's
      neurogenic phase. Additionally, salicytamide was effective in reducing
      carrageenan or croton oil-induced oedema formation. Overall, we have shown that
      salicytamide, proposed here as a new NSAID candidate, did not induce oral acute
      toxicity and elicited both peripheral antinociceptive effects (about 10-25 times
      more potent than its precursors in the writhing test) and antioedematogenic
      properties. Salicytamide also presented central antinociceptive activity, which
      seems to be mediated through opioid-independent mechanisms. These findings reveal
      salicytamide as a promising antinociceptive/antioedematogenic drug candidate.

PMID- 29654433
TI  - CpG-ODNs and Budesonide Act Synergistically to Improve Allergic Responses in
      Combined Allergic Rhinitis and Asthma Syndrome Induced by Chronic Exposure to
      Ovalbumin by Modulating the TSLP-DC-OX40L Axis.
AB  - The experimental model of combined allergic rhinitis and asthma syndrome (CARAS)
      has shown that CpG oligodeoxynucleotides (CpG-ODNs) are potential inhibitors of
      type 2 helper cell-driven inflammatory responses. Currently available CpG-ODNs
      modestly inhibit allergic responses in CARAS, while a combination strategy for
      upper airway treatment by co-administration of CpG-ODNs and glucocorticoids may
      show good efficacy. This study aimed to assess the therapeutic effects of CpG
      ODNs combined with budesonide (BUD) on upper and lower-airway inflammation and
      remodeling in mice with CARAS induced by chronic exposure to ovalbumin (OVA),
      exploring the possible underlying molecular mechanisms. A BALB/c mouse model of
      chronic CARAS was established by systemic sensitization and repeated challenge
      with OVA. Treatment with CpG-ODNs or BUD by intranasal administration was started
      1 h after OVA challenge. Then, nasal mucosa and lung tissues were fixed and
      stained for pathologic analysis. The resulting immunologic variables and TSLP-DC
      OX40L axis parameters were evaluated. Both CpG-ODNs and BUD intranasal
      administration are effective on reducing Th2-type airway inflammation and tissue
      remodeling. Co-administration of CpG-ODNs and BUD was more effective than each
      monotherapy in attenuating upper and lower-airway inflammation as well as airway
      remodeling in chronic CARAS. Notably, combination of CpG-ODNs with BUD modulated
      the TSLP-DC-OX40L axis, as demonstrated by decreased TSLP production in the nose
      and lung, alongside decreased TSLPR and OX40L in DC. Intranasal co-administration
      of CpG-ODNs and BUD synergistically alleviates airway inflammation and tissue
      remodeling in experimental chronic CARAS, through shared cellular pathways, as a
      potent antagonist of the TSLP-DC-OX40L axis.

PMID- 29654435
TI  - Risk factors and outcome of postoperative delirium after transcatheter aortic
      valve replacement.
AB  - BACKGROUND: POD is associated with a worse postoperative course in patients after
      cardiac surgery, but its incidence and effects after TAVR are not well
      understood. The aim of the present study was to analyze incidence, risk factors,
      and in-hospital outcomes of postoperative delirium (POD) after transfemoral (TF
      AVR) and transapical (TA-AVR) transcatheter aortic valve replacement (TAVR) in a
      nationwide cohort. METHODS AND RESULTS: Administrative data on all patients
      undergoing isolated TAVR in Germany in 2014 were analyzed. 9038 TF-AVR and 2522
      TA-AVR procedures were performed. POD incidence was 7% after TF-AVR and 12% after
      TA-AVR. Atrial fibrillation (TF: OR 1.35, p < 0.001; TA: OR 1.53, p = 0.001) and
      NYHA III/IV (TF: OR 1.23, p = 0.017, TA: OR 1.51, p = 0.001) were independent
      risk factors for POD. Dementia was a risk factor only in TF-AVR (OR 3.04, p <
      0.001). Female sex was protective (TF: OR 0.56, p < 0.001, TA: OR 0.51, p <
      0.001). We found the occurrence of POD to be associated with more postoperative
      complications such as stroke and bleeding. Consequently, patients with POD were
      ventilated and hospitalized longer and suffered an increased risk of in-hospital
      mortality (unadjusted OR TF: 1.83, p = 0.001, TA: 1.82, p = 0.01). After
      adjusting for postoperative events and comorbidities, POD's effect on in-hospital
      mortality disappeared. In contrast, stroke and bleeding remained independent
      predictors for mortality irrespective of POD. CONCLUSIONS: Patients with POD
      after TAVR are at increased risk for in-hospital mortality. However, after
      adjusting for postoperative events and comorbidities, stroke and bleeding, but
      not POD, are independent mortality predictors.

PMID- 29654434
TI  - Predictors for target lesion microcalcifications in patients with stable coronary
      artery disease: an optical coherence tomography study.
AB  - BACKGROUND: The minimal fibrous cap thickness overlying the necrotic lipid core
      as well as the presence of macrophages are established characteristics of
      coronary plaque vulnerability. Recently, the presence of microcalcifications has
      emerged as a novel feature of vulnerable lesions. However, clinical and plaque
      morphological predictors of microcalcifications are unknown. METHODS: In patients
      with stable coronary artery disease, analysis of plaque morphology (n = 112) was
      performed using optical coherence tomography prior to coronary intervention to
      assess predictors of microcalcifications. RESULTS: Microcalcifications were
      present in 21/112 (18.7%) lesions. Segments with microcalcifications showed a
      higher total number of calcifications per lesion (6.7 +/- 3.0 vs. 3.2 +/- 2.5, p
      < 0.001), a lower percent area stenosis (70.9 +/- 11.1 vs. 76.2 +/- 9.7%, p =
      0.028), and a higher frequency of macrophage infiltration (66.7 vs. 37.4%, p =
      0.014). In lesions with vs. without microcalcifications, macrophage infiltration
      was characterized by a wider macrophage angle (31.1 degrees  +/- 34.4 degrees 
      vs. 13.7 degrees  +/- 20.6 degrees , p = 0.003), a higher macrophage index (105.6
      +/- 269.0 vs. 31.6 +/- 66.5 degrees  mm, p = 0.020), and an increased frequency
      of calcium-macrophage co-localization (47.6 vs. 15.6%, p = 0.001). In
      multivariable logistic regression analysis, the total number of calcifications
      per lesion (OR 1.53, 95% CI 1.23-1.91, p < 0.001), average macrophage angle (OR
      1.28 for 10 degrees -variation, 95% CI 1.03-1.60, p = 0.024), and percent area
      stenosis (OR 0.59 for 10% increase, 95% CI 0.34-1.04, p = 0.070) were independent
      predictors for the presence of microcalcifications, whereas the latter did not
      reach statistical significance. CONCLUSION: Microcalcifications are related to a
      less advanced stenosis severity and to extensive plaque inflammation, but not to
      clinical parameters. Our data may add to the understanding and role of
      microcalcifications in coronary artery lesions.

PMID- 29654436
TI  - Public funding for medical research in relation to the burden of disease caused
      by cardiovascular diseases and neoplasms in Germany.
AB  - BACKGROUND: Public funding for medical research in Germany is primarily provided
      by the German Research Foundation (DFG) and the Federal Ministry of Education and
      Research (BMBF). The aim of this study was to analyze the amount of national
      public funding for medical research on predominant causes of death in Germany,
      cardiovascular diseases and neoplasms, in relation to the burden of these
      diseases in Germany. METHODS: Three evaluators categorized medical research
      projects funded by the DFG or BMBF between 2010 and 2012 into the categories
      "Diseases of the circulatory system" (with subgroups "Ischemic heart diseases",
      "Heart failure" and "Cerebrovascular diseases") and "Neoplasms". The total amount
      of public funding by the national agencies was analyzed in relation to the burden
      of disease for the respective disease condition. RESULTS: Information on national
      public funding for medical research of 2091 million euros was available; of
      those, 246.8 million euros (11.8%) were categorized being spent for research on
      "Neoplasms", 118.4 million euros (5.7%) for research on "Diseases of the
      circulatory system". This results in 362.08 euros per case of death, 16.58 euros
      per year of life lost (YLL) and 16.04 euros per disability-adjusted life year
      (DALY) for "Neoplasms" and in 113.44 euros per case of death, 8.05 euros per YLL
      and 7.17 euros per DALY for "Diseases of the circulatory system". CONCLUSIONS: In
      Germany, research on cardiovascular diseases receives a lower share of national
      public funding for medical research compared to oncological research. These
      results are comparable to other European countries.

PMID- 29654438
TI  - Acute coronary syndrome due to right coronary spasm and documented lambda-like J
      waves.

PMID- 29654437
TI  - Efficacy and safety of bivalirudin for percutaneous coronary intervention in
      acute coronary syndromes: a meta-analysis of randomized-controlled trials.
AB  - AIMS: The efficacy and safety of bivalirudin in patients undergoing percutaneous
      coronary intervention (PCI) for treatment of acute coronary syndromes (ACS)
      remains controversial despite recent evidence from large randomized-controlled
      trials (RCTs). Thus, this systematic review and meta-analysis sought to
      investigate the efficacy and safety of bivalirudin as compared to heparin in
      patients with ACS undergoing PCI. METHODS AND RESULTS: Medline/PubMed, Cochrane
      Central Register of Controlled Trials, and Clinical Trials.gov databases were
      searched for RCTs. Primary endpoint was MACE consisting of all-cause death,
      myocardial infarction, and stroke within 30 days. Secondary endpoints were
      components of the primary endpoint and stent thrombosis. The primary safety
      endpoint was major bleeding. We identified 12 RCTs comprising 33,844 patients.
      Between bivalirudin and heparin, there were no significant differences for MACE
      (OR 1.06; 95% CI 0.96-1.17; p = 0.24), death, myocardial infarction, and stent
      thrombosis. Similar results were seen following stratification by use of
      glycoprotein inhibitors (GPI). Major bleeding trended to be less frequent in
      patients treated with bivalirudin. However, no safety benefit for bivalirudin was
      seen when use of GPI was balanced between groups (OR 0.88; 95% CI 0.67-1.16; p =
      0.35; p for heterogeneity < 0.01). CONCLUSIONS: Compared with heparin,
      bivalirudin was associated with a similar incidence of ischemic events following
      PCI for ACS. An association of bivalirudin with decreased bleeding was not seen
      with balanced use of GPI.

PMID- 29654439
TI  - Adaptive servo-ventilation to treat central sleep apnea in heart failure with
      reduced ejection fraction: the Bad Oeynhausen prospective ASV registry.
AB  - BACKGROUND: Central sleep apnea (CSA) is highly prevalent in heart failure
      patients with reduced left ventricular ejection fraction (HF-REF). The Bad
      Oeynhausen Adaptive Servo-ventilation (ASV) registry (NCT01657188) was designed
      to investigate whether treatment of CSA with ASV improved survival in HF-REF
      patients; the effects of ASV on symptoms and cardiopulmonary performance were
      also investigated. METHODS AND RESULTS: From January 2004 to October 2013, the
      registry prospectively enrolled HF-REF patients [NYHA class >= II, left
      ventricular ejection fraction (LVEF) <= 45%] with moderate to severe predominant
      CSA [apnea-hypopnea index (AHI) >= 15/h]. ASV-treated patients were followed up
      at 3, 6, 12 and 24 months, including natriuretic peptide concentrations, blood
      gas analyses, echocardiography, 6-min walk distance (6MWD), and cardiopulmonary
      exercise (CPX) testing. 550 patients were included [age 67.7 +/- 10 years, 90%
      male, 52% in NYHA class >= III, LVEF 29.9 +/- 8%, AHI 35.4 +/- 13.6/h, and time
      with nocturnal oxygen saturation < 90% (T < 90%) 58 +/- 73 min]; ASV was
      prescribed to 224 patients. Over a median follow-up of 6.6 years, 109 (48.7%) ASV
      treated patients and 191 (58.6%) controls died (adjusted Cox modelling hazard
      ratio of 0.95, 95% confidence interval 0.68-1.24; p = 0.740); older age, lower
      LVEF, impaired renal function, low sodium concentration, and nocturnal hypoxemia
      were significant predictors of mortality. Patient reported NYHA functional class
      improved in the ASV group, but LVEF, CPX, 6MWD, natriuretic peptides and blood
      gases remained unchanged. CONCLUSIONS: Long-term ASV treatment of predominant CSA
      in HF-REF patients included in our registry had no statistically significant
      effect on survival. ASV improved HF symptoms, but had no significant effects on
      exercise capacity, LVEF, natriuretic peptide concentrations or blood gases during
      follow-up as compared to control patients.

PMID- 29654440
TI  - Management of cystic prolactinomas: a review.
AB  - INTRODUCTION: Cystic prolactinoma is a variant of prolactin-secreting pituitary
      adenoma. The strategies for the management of cystic prolactinoma have not been
      addressed thoroughly in clinical guidelines. METHODS: A literature search was
      performed using Pubmed to review the current approaches to the treatment of
      cystic prolactinoma. RESULTS: Transsphenoidal resection is an effective and
      relatively safe approach for the treatment of cystic prolactinoma, however,
      morbidity of surgery is dependent on the skill of the surgeon. Emerging studies
      allude to the efficacy and safety of dopamine agonists in the management of
      cystic prolactinoma. Dopamine agonists are associated with considerable rates of
      clinical improvement and tumor shrinkage, hence reducing the need for surgical
      intervention. CONCLUSIONS: Recent studies suggest that dopamine agonist therapy
      may be an effective and safe treatment option in a considerable portion of
      patients with cystic prolactinomas. We suggest that dopamine agonists should be
      considered as a first-line therapy for cystic prolactinoma in the absence of
      indications for early surgical intervention.

PMID- 29654441
TI  - Comment on Castien et al. (2018) pressure pain thresholds over the cranio
      cervical region in headache - a systematic review and meta-analysis.

PMID- 29654443
TI  - CT attenuation correction for thallium SPECT MPI and other benefits of
      multimodality imaging.

PMID- 29654444
TI  - Effect of reduced photon count levels and choice of normal data on semi-automated
      image assessment in cardiac SPECT.
AB  - BACKGROUND: The SMARTZOOM multifocal collimator from Siemens Healthcare was
      developed to improve the gamma-photon sensitivity in myocardial perfusion imaging
      without truncating the field of view. As part of the IQ-SPECT package, it may be
      used to reduce radiopharmaceutical dose to patients, as well as acquisition time.
      The aim of this study was twofold: (1) to evaluate the influence of dose
      reduction in semi-automated MPI scoring, with focus on different strategies for
      the choice of normal data (count-matched, full-count), and (2) to evaluate the
      effect of dose reduction afforded by Siemens' IQ-SPECT package. METHODS: 50
      patients underwent Tc-99m-sestamibi one-day stress/rest SPECT/CT. Multiple levels
      of count reduction were generated using binomial thinning. Using Corridor 4DM,
      summed stress score (SSS) was calculated using either count-matched or full-count
      normal data. Studies were classified as low-risk (SSS < 4) or intermediate/high
      risk (SSS >= 4). RESULTS: Count reduction using count-matched normal data
      increases false-normal rate and decreases sensitivity. With full-count normal
      data, count reduction increases false-hypoperfusion rate, leading to decreased
      specificity. Altogether, rate of reclassification was significant at roughly 67%
      dose and below. CONCLUSION: Significant bias results from count level of normal
      data relative to actual patient data. Compared to standard LEHR, IQ-SPECT should
      allow for significant dose reduction.

PMID- 29654442
TI  - Understanding Social Anxiety Disorder in Adolescents and Improving Treatment
      Outcomes: Applying the Cognitive Model of Clark and Wells (1995).
AB  - Social anxiety disorder is a condition characterised by a marked and persistent
      fear of being humiliated or scrutinised by others. Age-of-onset data point to
      adolescence as a developmentally sensitive period for the emergence of the
      condition, at a time when the peer group becomes increasingly important. Social
      anxiety in adolescence is associated with considerable impairment that persists
      through to adulthood. There are clear potential benefits to delivering effective
      interventions during adolescence. However, there is limited evidence on the
      specific efficacy of available therapies. This is in contrast to adults, for whom
      we have interventions with very specific treatment effects. One such treatment is
      individual cognitive therapy. Cognitive therapy is based on the cognitive model
      of social anxiety proposed by Clark and Wells (in: Heimberg, Leibowitz, Hope,
      Scheiber (eds) Social phobia: diagnosis, assessment and treatment, The Guilford
      Press, New York, 1995). The present review examines the potential application of
      this adult cognitive model to the understanding of adolescent social anxiety and
      considers additional adolescent-specific factors that need to be accommodated. It
      is suggested that a developmentally sensitive adoption of the cognitive model of
      social anxiety disorder (Clark and Wells 1995) for adolescents may lead to better
      treatment outcomes.

PMID- 29654445
TI  - Noninvasive estimation of quantitative myocardial blood flow with Tc-99m MIBI by
      a compartment model analysis in rat.
AB  - BACKGROUND: We aimed to investigate the use of dynamic cardiac planar images to
      estimate myocardial blood flow (MBF) by a compartment model analysis using time
      to-peak (TP) map and compared it by the microsphere technique in rat. Positron
      emission tomography is considered the gold standard method, but is not available
      everywhere. By contrast, although myocardial perfusion imaging (MPI) with single
      photon tracers is more widely available, it may be difficult to obtain adequate
      region of interest (ROI) settings. We proposed using the TP map to set the ROI,
      and hypothesized that this method could facilitate the measurement of absolute
      MBF by MPI in rat. METHODS: Twenty-one normal rats were studied. Dynamic planar
      images with Tc-99m MIBI were obtained, and input function and cardiac ROIs were
      set using the obtained TP map. MBF was estimated by a one-compartment model
      analysis with the Renkin-Crone model and by the microsphere technique. RESULTS:
      The MBFs from these two methods were significantly correlated. A negative
      proportional bias was observed, but no significant difference was observed
      between the mean MBFs calculated with each method. CONCLUSIONS: MBF estimation by
      a compartment model analysis using TP map could facilitate absolute MBF
      measurement in rats.

PMID- 29654446
TI  - Count density curves for gated SPECT myocardial perfusion imaging studies: An
      overview of technical considerations, patterns in various arrhythmia-related
      artifacts, and a technologist's guide for curve plotting.

PMID- 29654447
TI  - Efficacy and Safety of Stents in the Treatment of Fistula After Bariatric
      Surgery: a Systematic Review and Meta-analysis.
AB  - Fistula development is a serious complication after bariatric surgery. We
      performed a systematic review and meta-analysis to assess the efficacy of fistula
      closure and complications associated with endoscopic stent treatment of fistulas,
      developed after bariatric surgeries, particularly Roux-en-Y gastric bypass (RYGB)
      and gastric sleeve (GS). Studies involving patients with fistula after RYGB or GS
      and those who received stent treatment only were selected. The analyzed outcomes
      were overall success rate of fistula closure, mean number of stents per patient,
      mean stent dwelling time, and procedure-associated complications. Current
      evidence from identified studies demonstrates that, in selected patients,
      endoscopic stent treatment of fistulas after GS or RYGB can be safe and
      effective.

PMID- 29654448
TI  - The course of acquired von Willebrand syndrome during pregnancy among patients
      with essential thrombocytosis.
AB  - To investigate the course of acquired type 2A von Willebrand syndrome (AVWS) in
      relation to patient management and outcomes among pregnant patients with
      essential thrombocytosis (ET). A review of pregnant women with ET evaluated for
      AVWS at the beginning of pregnancy and at the third trimester. Eighteen women
      with 24 pregnancies were included in this study. A history of bleeding was noted
      in 8 (44%) patients. In 20 (83%) pregnancies AVWS was evident at the initial
      testing. Following initial testing, antithrombotic therapy was administered in 22
      (92%) pregnancies (aspirin, n = 20 and low-molecular-weight heparin, n = 2). In
      the remaining two pregnancies, VWF:RCo levels were below 30%; thus, aspirin was
      given only after repeat testing at 14-16 weeks. At third trimester testing,
      median VWF:RCo levels were significantly higher than at the initial testing (86
      vs. 48%, P < 0.001), with no evidence of AVWS in any of the patients. Significant
      increases were also observed in the VWF:Ag level (127 vs. 84%, P < 0.001), the
      VWF:RCo/VWF:Ag ratio (0.75 vs. 0.54, P < 0.001) and the FVIII level (103 vs. 68%,
      P < 0.001); while platelet count (359 vs. 701 * 109/l, P < 0.001) and hemoglobin
      level (11.6 vs. 13.4 g/dl, P < 0.001) decreased. Neuraxial anesthesia was safely
      performed in 17 (71%) pregnancies. No significant bleeding events occurred during
      pregnancy and delivery. AVWS-related abnormalities in women with ET mostly
      improved during pregnancy, with favorable maternal and fetal outcomes. VWF
      parameters should be tested at early pregnancy and repeated at the third
      trimester, to guide pregnancy and delivery management.

PMID- 29654449
TI  - Transcatheter valve interventions in heart failure: new answers to old questions.
AB  - Heart failure (HF) is often associated with different valve diseases,
      predominantly functional mitral and tricuspid regurgitation. However, the
      association between HF and aortic stenosis, particularly low-flow low-gradient
      aortic stenosis, is not infrequent. Severe mitral and tricuspid regurgitations,
      as well as aortic stenosis, in HF patients worsen prognosis and left ventricular
      dilatation and induce further reduction in left ventricular ejection fraction.
      Transcatheter edge-to-edge mitral and tricuspid valve repair and transcatheter
      aortic valve implantation could be an important therapeutic option with a
      satisfactory long-term outcome in HF patients with comorbidities and even in
      patients with severely depressed ejection fraction.

PMID- 29654450
TI  - Elevated Troponin in the First 72 h of Hospitalization for Pediatric Viral
      Myocarditis is Associated with ECMO: An Analysis of the PHIS+ Database.
AB  - Serum troponin (Tn) is often elevated in viral myocarditis; however, its
      prognostic significance is unknown. We tested the hypothesis that abnormal serum
      Tn is associated with mortality in children hospitalized with myocarditis. We
      retrospectively studied data from six large children's hospitals participating in
      the Pediatric Health Information System Plus (PHIS+) database. Analysis was
      performed on patients hospitalized with viral myocarditis between 2007 and 2013,
      in whom at least one Tn was recorded within 72 h of admission. Abnormal baseline
      Tn was defined as any value outside the upper limit of normal within the first 72
      h. Primary outcome was mortality. Secondary outcomes included mechanical support,
      defined as use of extracorporeal membrane oxygenation (ECMO) or a ventricular
      assist device (VAD), cardiac transplantation, intravenous immunoglobulin (IVIg),
      mechanical ventilation, and inotrope use. A total of 149 patients with
      myocarditis (61% male, 48% adolescents) across all PHIS+ centers had TnI (n =
      113) or TnT (n = 36) recorded. At least one abnormal Tn was present in 81% of
      cases. Overall mortality was 7.3% and was not associated with abnormal baseline
      Tn. Abnormal baseline Tn was associated with ECMO (7.1 vs. 25.6%, p = 0.03) and
      IVIg (46.4 vs. 83.5%, p < 0.001). Abnormal baseline Tn was not associated with
      transplantation, mechanical ventilation or inotrope use. Abnormal Tn in the first
      72 h of hospitalization for myocarditis was associated with the use of ECMO and
      IVIg, but was not associated with mortality. This finding may help risk stratify
      this population if it can be prospectively validated.

PMID- 29654451
TI  - Adults with Autism Tend to Undermine the Hidden Environmental Structure: Evidence
      from a Visual Associative Learning Task.
AB  - The learning-style theory of Autism Spectrum Disorders (ASD) (Qian, Lipkin,
      Frontiers in Human Neuroscience 5:77, 2011) states that ASD individuals differ
      from neurotypics in the way they learn and store information about the
      environment and its structure. ASD would rather adopt a lookup-table strategy
      (LUT: memorizing each experience), while neurotypics would favor an interpolation
      style (INT: extracting regularities to generalize). In a series of visual
      behavioral tasks, we tested this hypothesis in 20 neurotypical and 20 ASD adults.
      ASD participants had difficulties using the INT style when instructions were
      hidden but not when instructions were revealed. Rather than an inability to use
      rules, ASD would be characterized by a disinclination to generalize and infer
      such rules.

PMID- 29654452
TI  - Autistic Traits in Treatment-Seeking Transgender Adults.
AB  - The present study aimed to compare prevalence of autistic traits measured by the
      self-reported autism spectrum quotient-short (AQ-short) in a transgender clinical
      population (n = 656) matched by age and sex assigned at birth to a cisgender
      community sample. Results showed that transgender and cisgender people reported
      similar levels of possible autistic caseness. Transgender people assigned female
      were more likely to have clinically significant autistic traits compared to any
      other group. No difference was found between those assigned male. High AQ scores
      may not be indicative of the presence of an autism spectrum condition as the
      difference between groups mainly related to social behaviours; such scores may be
      a reflection of transgender people's high social anxiety levels due to negative
      past experiences.

PMID- 29654453
TI  - State-Level Trends in the Prevalence of Autism Spectrum Disorder (ASD) from 2000
      to 2012: A Reanalysis of Findings from the Autism and Developmental Disabilities
      Network.
AB  - Since 2000, the Autism and Developmental Disabilities Network (ADDM) has
      published detailed prevalence estimates for autism spectrum disorder (ASD) among
      8 year-olds, which are widely interpreted as the U.S. national prevalence of ASD.
      Although differences in state-level ASD prevalence has been reported, state-level
      heterogeneity has not been explored systematically. We analyzed state-level
      estimates and trends in ASD prevalence from 2000 to 2012 using secondary data
      from bi-annual ADDM reports. Heterogeneity among state-level ASD prevalence
      estimates were apparent in 2000 and grew between 2000 and 2012. Findings
      highlight the need for greater understanding of how children with ASD are
      identified by the medical and educational systems, which has significant
      implications for the state-level resources required to effectively manage ASD.

PMID- 29654454
TI  - In situ co-precipitation preparation of a superparamagnetic graphene oxide/Fe3O4
      nanocomposite as an adsorbent for wastewater purification: synthesis,
      characterization, kinetics, and isotherm studies.
AB  - A superparamagnetic graphene oxide (GO)/Fe3O4 nanocomposite (MGO) was prepared by
      a facile in situ co-precipitation strategy, resulting in a prospective material
      for the application of graphene oxide in wastewater treatment. MGO was
      characterized by scanning electron microscopy (SEM), transmission electron
      microscopy (TEM), x-ray diffraction (XRD), and Fourier transform infrared
      spectroscopy (FTIR). The prepared adsorbent showed a high adsorption efficiency
      relevant to the purification of dye-contaminated wastewater and could be readily
      magnetically separated. The maximum adsorption capacity was ca. 546.45 mg g-1 for
      the common cationic dye methylene blue (MB) and ca. 628.93 mg g-1 for the anionic
      dye Congo red (CR). The adsorption processes fit the pseudo-second-order kinetic
      model well, which revealed that these processes may involve the chemical
      interaction between adsorbate and adsorbent. The thermodynamic parameters
      indicated that the adsorption reaction was an endothermic and spontaneous
      process. Furthermore, the prepared magnetic adsorbent had a wide effective pH
      range from 5 to 11 and showed good stability after five reuse cycles. The
      synthetic MGO showed great potential as a promising adsorbent for organic
      contaminant removal in wastewater treatment.

PMID- 29654455
TI  - Fumaric acid production using renewable resources from biodiesel and cane sugar
      production processes.
AB  - The microbial production of fumaric acid by Rhizopus arrhizus NRRL 2582 has been
      evaluated using soybean cake from biodiesel production processes and very high
      polarity (VHP) sugar from sugarcane mills. Soybean cake was converted into a
      nutrient-rich hydrolysate via a two-stage bioprocess involving crude enzyme
      production via solid state fermentations (SSF) of either Aspergillus oryzae or R.
      arrhizus cultivated on soybean cake followed by enzymatic hydrolysis of soybean
      cake. The soybean cake hydrolysate produced using crude enzymes derived via SSF
      of R. arrhizus was supplemented with VHP sugar and evaluated using different
      initial free amino nitrogen (FAN) concentrations (100, 200, and 400 mg/L) in fed
      batch cultures for fumaric acid production. The highest fumaric acid
      concentration (27.3 g/L) and yield (0.7 g/g of total consumed sugars) were
      achieved when the initial FAN concentration was 200 mg/L. The combination of VHP
      sugar with soybean cake hydrolysate derived from crude enzymes produced by SSF of
      A. oryzae at 200 mg/L initial FAN concentration led to the production of 40 g/L
      fumaric acid with a yield of 0.86 g/g of total consumed sugars. The utilization
      of sugarcane molasses led to low fumaric acid production by R. arrhizus, probably
      due to the presence of various minerals and phenolic compounds. The promising
      results achieved through the valorization of VHP sugar and soybean cake suggest
      that a focused study on molasses pretreatment could lead to enhanced fumaric acid
      production.

PMID- 29654456
TI  - Phthalate esters distribution in coastal mariculture of Hong Kong, China.
AB  - The aim of the study is to evaluate the impact of mariculture on phthalate esters
      speciation and distribution in sediments and cultured fish in the Hong Kong
      regions and near mainland China. Concentrations of ?phthalate esters in
      mariculture surface sediments (0 to 5 cm) ranged from 0.20 to 54.3 mg/kg dw (mean
      10.3 mg/kg dw), with the highest recorded at M2 (20.4 mg/kg dw). Concentrations
      of phthalate esters were not significantly (p > 0.05) enriched in surface and
      sediment cores at mariculture sites relative to the reference sediments, 1 to 2
      km away in areas without mariculture activities. Among different congeners, only
      butyl benzyl phthalate (BBP) concentrations demonstrated a significant
      correlation (R2 = 0.40, p < 0.05) with TOC values of sediments. The median
      concentrations of di-2-ethylhexyl phthalate (DEHP) and di-n-butyl phthalate (DBP)
      in the sediments were 1.57 and 6.96 times higher than the environmental risk
      levels (ERL), which may pose environmental risks. Results of health risk
      assessments revealed that the cultured fish (snubnose pompano, orange-spotted
      grouper, and red snapper) were safe for consumption, in terms of phthalate
      esters. This is the first study to assess the differences of phthalate esters
      contamination between mariculture and natural coastal sediments.

PMID- 29654457
TI  - Investigation of the physical and chemical characteristics of rural solid waste
      in China and its spatiotemporal distributions.
AB  - Despite governmental efforts toward the development of policies, funds, and
      technologies, the inherent characteristics of rural solid waste (RSW) discharge
      have led to great difficulties in RSW pollution control. However, establishing a
      realistic management strategy requires greater knowledge of RSW generation.
      Therefore, the RSW of 72 typical towns and villages from 12 provinces of China
      was analyzed for physicochemical characteristics, as well as its spatiotemporal
      distribution. The largest proportion of kitchen waste, coal ash, plastic, and
      paper of RSW was 33.70% +/- 17.87%, 26.50% +/- 17.61%, 13.48% +/- 5.68%, and
      10.75% +/- 5.75%, respectively, in 2015. Although RSW had the potential for
      composting, it was still necessary to pay special attention to heavy metals
      pollution of RSW. The spatiotemporal distributions of RSW components were
      extremely non-homogenous, and significant variations existed in the kitchen
      residue, coal ash, plastic, and paper because of differences in economic growth,
      climatic changes, dietary habits, energy consumption structure, and consumer
      preferences. No obvious differences in RSW components were observed between
      villages and market towns. Overall, RSW treatment and management approaches
      should be considered based on local conditions of RSW generation.

PMID- 29654458
TI  - Towards pesticide-free farming? Sharing needs and knowledge promotes Integrated
      Pest Management.

PMID- 29654460
TI  - Panel estimation for renewable and non-renewable energy consumption, economic
      growth, CO2 emissions, the composite trade intensity, and financial openness of
      the commonwealth of independent states.
AB  - This article investigates the long-run and causal linkages between economic
      growth, CO2 emissions, renewable and non-renewable (fossil fuels) energy
      consumption, the Composite Trade Intensity (CTI) as a proxy for trade openness,
      and the Chinn-Ito index as a proxy for financial openness for a panel of the
      Commonwealth of Independent States (CIS) region including Armenia, Azerbaijan,
      Belarus, Georgia, Kazakhstan, Kyrgyzstan, Moldova, Russia, Tajikistan,
      Turkmenistan, Ukraine, and Uzbekistan over the period of 1992-2015. It is the
      first time that CTI and the Chinn-Ito indexes are used in an economic-pollution
      model. Employing three panel unit root tests, panel cointegration estimation
      methods (DOLS and FMOLS), and two panel causality tests, the main empirical
      results provided evidence for the bidirectional long-run relationship between all
      the variables in all 12 sampled countries except for economic growth-renewable
      energy use linkage. The findings of causality tests indicated that there is a
      unidirectional short-run panel causality running from economic growth, financial
      openness, and trade openness to CO2 emissions and from fossil fuel energy
      consumption to renewable energy use.

PMID- 29654459
TI  - Emergency material allocation with time-varying supply-demand based on dynamic
      optimization method for river chemical spills.
AB  - Aiming to minimize the damage caused by river chemical spills, efficient
      emergency material allocation is critical for an actual emergency rescue decision
      making in a quick response. In this study, an emergency material allocation
      framework based on time-varying supply-demand constraint is developed to allocate
      emergency material, minimize the emergency response time, and satisfy the dynamic
      emergency material requirements in post-accident phases dealing with river
      chemical spills. In this study, the theoretically critical emergency response
      time is firstly obtained for the emergency material allocation system to select a
      series of appropriate emergency material warehouses as potential supportive
      centers. Then, an enumeration method is applied to identify the practically
      critical emergency response time, the optimum emergency material allocation and
      replenishment scheme. Finally, the developed framework is applied to a
      computational experiment based on south-to-north water transfer project in China.
      The results illustrate that the proposed methodology is a simple and flexible
      tool for appropriately allocating emergency material to satisfy time-dynamic
      demands during emergency decision-making. Therefore, the decision-makers can
      identify an appropriate emergency material allocation scheme in a balance between
      time-effective and cost-effective objectives under the different emergency
      pollution conditions.

PMID- 29654461
TI  - Effect of biochar derived from barley straw on soil physicochemical properties,
      crop growth, and nitrous oxide emission in an upland field in South Korea.
AB  - This study was conducted to investigate soil quality, Chinese cabbage growth, and
      N2O emission after biochar application in an upland field in South Korea. Each of
      the barley straw biochar (BC, applied at 10 ton ha-1), inorganic fertilizer (IF,
      applied at N-P-K = 320-78-198 kg ha-1), and BC + IF treatment areas were
      separated by a control (Cn) treatment area. Soils treated with BC and BC + IF
      treatments had lower bulk density and higher porosity than those in the Cn
      treatment areas. Soil chemical properties (pH, TN, Avail. P2O5, and CEC) after
      biochar addition were improved. In particular, soil pH and CEC related to crop
      nutrient availability were significantly increased in BC areas compared to those
      in Cn and IF areas. Fresh weights of Chinese cabbage grown under BC, IF, and BC +
      IF treatment conditions increased by 64.9, 78.4, and 112.0%, respectively, over
      that in the Cn treatment area. Total nutrient (TN, TP, and K) uptakes among the
      treatment areas were, in declining order, BC + IF (14.51 g plant-1) > IF > BC >
      Cn. More interestingly, the BC application had a positive effect on growth of
      Chinese cabbage under IF application conditions, and there was a tight
      relationship between the effect of BC application on Chinese cabbage growth and
      that of agronomic IF application efficiency. Compared to the IF results, total
      N2O flux was lower with BC (flux decreased by 60.6%) or BC + IF (flux decreased
      by 22.3%) treatments. These results indicate that Chinese cabbage yield, when
      cultivated in soil conditions such as those in an upland field in South Korea,
      can be increased by application of BC or a combination of BC and IF.

PMID- 29654462
TI  - Flux model to estimate the transport of mercury species in a contaminated lagoon
      (Ria de Aveiro, Portugal).
AB  - The concentrations of dissolved and particulate inorganic mercury (IHg(II)) and
      methylmercury (MeHg) from the contaminated Laranjo Bay (main freshwater discharge
      from the Antua River) were measured by species-specific isotope dilution during
      six sampling campaigns at high and at low tide. Different effective riverine
      concentrations were calculated, based on salinity profiles, for specific
      hydrological conditions. The export fluxes of total Hg and MeHg (324 and 1.24 mol
      year-1, respectively) from the bay to the rest of the Aveiro Lagoon are much
      higher than the input fluxes from the Hg source (3.9 and 0.05 mol year-1) and
      from the Antua River (10.4 and 0.10 mol year-1). Resuspension of contaminated
      sediments from Laranjo Bay is crucial for the transport of both IHg(II) and MeHg.
      Methylation and/or selective enrichment into biogenic particles is responsible
      for the mobilization of MeHg. Sorption of dissolved IHg(II) onto suspended
      particles limits its export flux. This is one of the rarest examples where both
      speciation fluxes and partitioning of mercury are studied in a contaminated
      coastal environment. Despite the lower fraction of total MeHg (relative to total
      Hg), the contaminated lagoon may have an impact on coastal areas, particularly if
      change in the lagoon geometry occurs, due to sea level rise.

PMID- 29654463
TI  - Valorisation of tuna processing waste biomass: isolation, purification and
      characterisation of four novel antioxidant peptides from tuna by-product
      hydrolysate.
AB  - Tuna protein hydrolysate (TPH) was prepared by hydrolysis with Prolyve BS and
      fractionated by membranes process. The antioxidant activities of recovered
      peptide fractions were evaluated. Four novel antioxidant peptides that were
      isolated from nanofiltration retentate exhibited the highest antioxidant
      activity, using gel chromatography and reversed phase high-performance liquid
      chromatography. The amino acid sequences of isolated peptides were identified as
      Tyr-Glu-Asn-Gly-Gly (P2), Glu-Gly-Tyr-Pro-Trp-Asn (P4), Tyr-Ile-Val-Tyr-Pro-Gly
      (P7) and Trp-Gly-Asp-Ala-Gly-Gly-Tyr-Tyr (P8) with molecular weights of 538.46,
      764.75, 710.78 and 887.85 Da, respectively. P2, P4, P7 and P8 exhibited good
      scavenging activities on hydroxyl radical (IC50 0.41, 0.327, 0.17 and 0.042
      mg/ml), DPPH radical (IC50 0.666, 0.326, 0.451 and 0.377 mg/ml) and superoxide
      radical (IC50 0.536, 0.307, 0.357 and 0.115 mg/ml). P7 was effective against
      lipid peroxidation in the model system. The isolated peptides might be useful
      used as natural food additive in food industry and formulation of nutritional
      products.

PMID- 29654464
TI  - Biodegradation of CuTETA, an effluent by-product in mineral processing.
AB  - Polyamines such as triethylenetetramine (TETA) and other amine chelators are used
      in mineral processing applications. Formation of heavy metal complexes of these
      reagents as a by-product in effluent water is a recent environmental concern. In
      this study, Paecilomyces sp. was enriched from soil on TETA as the sole source of
      carbon and nitrogen and was found to degrade > 96 and 90% CuTETA complexes at
      initial concentrations of 0.32 and 0.79 mM respectively, following 96-h
      incubation. After destabilization, most of the copper (> 78%) was complexed
      extracellularly and the rest was associated with the cell. Mass spectroscopy
      results provided confirmation that copper re-complexed with small, extracellular,
      and organic molecules. There are no reports in the literature that Paecilomyces
      or any other organism can grow on TETA or CuTETA. This study is the first to show
      that biological destabilization of CuTETA complexes in mineral processing
      effluents is feasible.

PMID- 29654465
TI  - Incorporation of zinc and copper by insects of different functional feeding
      groups in agricultural streams.
AB  - Metals from agricultural areas are responsible for soil contamination and are
      carried into aquatic ecosystems. In this context, we evaluated the incorporation
      of zinc and copper via three feeding strategies (shredding, herbivory and
      predators) in assemblages of stream insects. We collected aquatic insects in five
      agricultural streams and five natural streams in Atlantic forest biome to
      investigate the accumulation of copper and zinc in insects with different feeding
      strategies. We found no significant differences in the concentrations of copper
      and zinc between stream types among all insect-feeding groups compared. However,
      we observed that copper accumulate concentrations differed significantly among
      the shredders and predators in relation to their resource in streams, while zinc
      concentrations differed in the two feeding strategy. Therefore, the investigation
      of the transfer of copper and zinc by different feeding strategies in streams can
      contribute to the understanding of changes in aquatic insect assemblages related
      to agricultural activities around streams.

PMID- 29654466
TI  - Polycyclic aromatic hydrocarbon (PAH) levels in environmental media potentially
      impacted by reused or stored creosote-treated railway ties.
AB  - Disused creosote-treated railway ties are reused in France and many other
      countries and, in particular, for landscaping and other residential uses. Given
      the lack of data on the environmental fate of creosote-derived compounds released
      from used railway ties, a survey of different environmental media (i.e. soil,
      sediment, surface water, plants and outdoor air) was carried out at six sites
      located in France where old creosote-treated railway ties are stored or reused
      for different purposes. Maximum total polycyclic aromatic hydrocarbon (PAH)
      concentrations measured in soils ranged from 2 to 140 mg/kg dry weight. PAH
      impacts were limited both vertically and horizontally to several centimetres from
      the railway ties. At two sites, PAH levels in plants (up to 140 MUg/kg fresh
      weight) appeared correlated to the levels measured in soils, suggesting a
      transfer from soils to the plants. PAHs in sediment were measured at
      concentrations of up to 280 mg/kg dry weight. As observed in soil, PAH
      concentrations decreased rapidly further away from the railway ties. Principal
      component analysis and hierarchical clustering on principal components indicate
      that PAHs detected in soils and sediments originated from unweathered to severely
      weathered creosote and could be strongly influenced by urban background. Results
      on outdoor air measurements show a degradation of air quality above old and fresh
      railway tie storage areas at a railway station and to a lesser extent in their
      vicinity. However, this degradation was low to moderate when compared to French
      regulatory values, ambient background levels reported in France, as well as
      health-based air comparison values.

PMID- 29654467
TI  - Arcopilus aureus, a Resveratrol-Producing Endophyte from Vitis vinifera.
AB  - Resveratrol is extensively being used as a therapeutic moiety, as well as a
      pharmacophore for development of new drugs due to its multifarious beneficial
      effects. The objective of the present study was to isolate and screen the
      resveratrol-producing endophytic fungi from different varieties of Vitis
      vinifera. A total of 53 endophytic fungi belonging to different fungal genera
      were isolated from the stem and leaf tissues of Vitis vinifera (merlot, wild,
      pinot noir, Shiraz, muscat) from different grape-producing locations of India.
      Only 29 endophytic fungal isolates exhibited a positive test for phenolics by
      phytochemical methods. The resveratrol obtained after ethyl acetate extraction
      was confirmed using standard molecule on thin layer chromatography (TLC) with a
      retention factor (Rf) of 0.69. The purified and standard resveratrol were
      visualized under UV light as a violet-colored spot. In HPLC analysis of the ethyl
      acetate extract of culture broth of 11 endophytic isolates, the highest
      resveratrol content was found in #12VVLPM (89.1 MUg/ml) followed by #18VVLPM
      (37.3 MUg/ml) and 193VVSTPM (25.2 MUg/ml) exhibiting a retention time of 3.36 min
      which corresponded to the standard resveratrol. The resveratrol-producing
      isolates belong to seven genera viz. Aspergillus, Botryosphaeria, Penicillium,
      Fusarium, Alternaria, Arcopilus, and Lasiodiplodia, and using morphological and
      molecular methods, #12VVLPM was identified as Arcopilus aureus.

PMID- 29654468
TI  - Efficient Biotransformation of Phytosterols to Dehydroepiandrosterone by
      Mycobacterium sp.
AB  - In this study, a method for the efficient production of dehydroepiandrosterone
      (DHEA) from phytosterols in a vegetable oil/aqueous two-phase system by
      Mycobacterium sp. was developed. After the 3-hydroxyl group of phytosterols was
      protected, they could be converted into DHEA with high yield and productivity by
      Mycobacterium sp. NRRL B-3683. In a shake flask biotransformation, 15.05 g l-1 of
      DHEA and a DHEA yield of 85.39% (mol mol-1) were attained after 7 days with an
      initial substrate concentration of 25 g l-1. When biotransformation was carried
      out in a 30-l stirred bioreactor with 25 g l-1 substrate, the DHEA concentration
      and yield was 16.33 g l-1 and 92.65% (mol mol-1) after 7 days, respectively. The
      results of this study suggest that inexpensive phytosterols could be utilized for
      the efficient production of DHEA.

PMID- 29654470
TI  - [Parental Alienation (Syndrome) - A serious form of child psychological abuse].
AB  - Induced parental alienation is a specific form of psychological child abuse,
      which is listed in DSM-5, the current Diagnostic and Statistical Manual of the
      American Psychiatric Association (APA), under diagnostic code V 995.51 "child
      psychological abuse". Untreated induced parental alienation can lead to long-term
      traumatic psychological and physical effects in the children concerned. This fact
      is still not given sufficient attention in family court cases. The article gives
      a condensed overview of parental alienation, summarising its definition, the
      symptoms and the various levels of severity. It also describes some major
      alienation techniques and possible psychosomatic and psychiatric effects of
      induced parental alienation. Finally, attention is drawn to programmes of
      prevention and intervention now used and evaluated in some countries. The article
      concludes with two real-life examples from psychiatric practice, and a
      comprehensive list of international references.

PMID- 29654469
TI  - Sulfur-Based Ylides in Transition-Metal-Catalysed Processes.
AB  - Traditionally employed in the synthesis of small ring systems and rearrangement
      chemistry, sulfur-based ylides occupy a unique position in the toolbox of the
      synthetic organic chemist. In recent years a number of pioneering researchers
      have looked to expand the application of these unorthodox reagents through the
      use of transition metal catalysis. The strength and flexibility of such a
      combination have been shown to be of key importance in developing powerful novel
      methodologies. This chapter summarises recent developments in transition metal
      catalysed sulfonium/sulfoxonium ylide reactions, as well as providing a
      historical perspective. In overviewing the successes in this area, the authors
      hope to encourage others into this growing field.

PMID- 29654471
TI  - Haloquadratum walsbyi Yields a Versatile, NAD+/NADP+ Dual Affinity, Thermostable,
      Alcohol Dehydrogenase (HwADH).
AB  - This study presents the first example of an alcohol dehydrogenase (ADH) from the
      halophilic archaeum Haloquadratum walsbyi (HwADH). A hexahistidine-tagged
      recombinant HwADH was heterologously overexpressed in Haloferax volcanii. HwADH
      was purified in one step and was found to be thermophilic with optimal activity
      at 65  degrees C. HwADH was active in the presence of 10% (v/v) organic solvent.
      The enzyme displayed dual cofactor specificity and a broad substrate scope, and
      maximum activity was detected with benzyl alcohol and 2-phenyl-1-propanol. HwADH
      accepted aromatic ketones, acetophenone and phenylacetone as substrates. The
      enzyme also accepted cyclohexanol and aromatic secondary alcohols, 1
      phenylethanol and 4-phenyl-2-butanol. H. walsbyi may offer an excellent
      alternative to other archaeal sources to expand the toolbox of halophilic
      biocatalysts.

PMID- 29654472
TI  - Dietary Supplementation of Probiotic Bacillus subtilis Affects Antioxidant
      Defenses and Immune Response in Grass Carp Under Aeromonas hydrophila Challenge.
AB  - This study investigated whether Bacillus subtilis can provide protection for
      grass carp against oxidative stress damage induced by Aeromonas hydrophila. A
      total of 240 healthy grass carp (Ctenopharyngodon idellus) (average weight of
      71.42 +/- 4.36g) were randomly divided into four groups with three replicates:
      control group, A. hydrophila group, B. subtilis + A. hydrophila group, and A.
      hydrophila + B. subtilis group. After challenge with A. hydrophila, the lipid
      oxidative damage, antioxidant defenses, and the gene expression of inflammatory
      cytokines of the grass carp were investigated. Our results showed that A.
      hydrophila caused lipid oxidative damage, led to significant decreases in
      antioxidant defenses, and induced inflammatory responses of grass carp. However,
      the grass carp group fed the probiotic B. subtilis diet for 42 days before the
      challenge and the group fed the probiotic B. subtilis diet immediately after the
      challenge both showed (i) a reduced level of oxidative stress with a decrease in
      the level of MDA; (ii) an increase in antioxidant defenses, including an increase
      in total antioxidant capacity (T-AOC), increased activities of SOD and CAT,
      increased levels of GSH, and upregulated gene expression of antioxidant enzymes
      (SOD, CAT, and Gpx); and (iii) an improved immune response with the level of
      antiinflammatory cytokines IL-10 messenger RNA (mRNA) upregulated and the levels
      of pro-inflammatory cytokines TNF-alpha, IL-1beta, and IL-8 mRNA downregulated.
      Based on this study, B. subtilis can provide effective protection of fish against
      oxidative stress damage induced by A. hydrophila infection.

PMID- 29654473
TI  - Isolation and Preliminary Screening of a Weissella confusa Strain from Giant
      Panda (Ailuropoda melanoleuca).
AB  - Weissella confusa has recently received attention for its probiotic potential.
      Some W. confusa and Weissella cibaria strains isolated from fermented foods show
      favorable probiotic effects. However, the probiotic properties of W. confusa
      isolated from giant panda remain unreported to date. Thus, this study isolated a
      W. confusa strain from giant panda feces and then investigated its
      characteristics and probiotic properties. A lactic acid bacteria strain was
      isolated from giant panda fecal samples. The isolated strain was screened by in
      vitro probiotic property tests, including in vitro antimicrobial test,
      antioxidant test, surface hydrophobicity, and stress resistance. On the basis of
      biochemical identification and 16S rDNA sequencing, the W. confusa strain was
      identified as BSP201703. This Weissella confusa strain can survive at pH 2 and
      0.3% (w/v) concentration of bile salt environment and inhibit common intestinal
      pathogens. It also possesses an in vitro antioxidant capacity, a high auto
      aggregation ability, and a high surface hydrophobicity. BSP201703 might serve as
      a probiotic to giant pandas.

PMID- 29654474
TI  - Plant Growth Enhancement, Disease Resistance, and Elemental Modulatory Effects of
      Plant Probiotic Endophytic Bacillus sp. Fcl1.
AB  - Endophytic bacteria have already been studied for their beneficial support to
      plants to manage both biotic and abiotic stress through an array of well
      established mechanisms. They have either direct or indirect impact on mobilizing
      diverse nutrients and elements from soil to plants. However, detailed insight
      into the fine-tuning of plant elemental composition by associated microorganism
      is very limited. In this study, endophytic Bacillus Fcl1 characterized from the
      rhizome of Curcuma longa was found to have broad range of plant growth-promoting
      and biocontrol mechanisms. The organism was found to have indole acetic acid and
      1-aminocyclopropane-1-carboxylate deaminase production properties along with
      nitrogen fixation. The Bacillus Fcl1 could also inhibit diverse phytopathogens as
      confirmed by dual culture and well diffusion. By LC-MS/MS analysis, chemical
      basis of its antifungal activity has been proved to be due to the production of
      iturin A and a blend of surfactin compounds. Moreover, the organism was found to
      induce both plant growth and disease resistance in vivo in model plant system.
      Because of these experimentally demonstrated multiple plant probiotic features,
      Bacillus Fcl1 was selected as a candidate organism to study its role in
      modulation of plant elemental composition. ICP-MS analysis of Bacillus Fcl1
      treated plants provided insight into relation of bacterial interaction with
      elemental composition of plants.

PMID- 29654475
TI  - NMR comparison of hyphal and yeast Candida albicans serotype B mannans.
AB  - A change from a globular to a filamentous hyphal form is an important feature in
      the pathogenicity of yeasts. Such a dimorphism while infecting a host organism is
      thought to be also accompanied in the case of Candida albicans spp. by a
      structural rearrangement of surface mannan antigen. The presented work brings new
      insights into the molecular structural changes of mannan C. albicans serotype B
      based on NMR experimental data. 1H and 13C signal identification of the anomeric
      region and the assignment of their linkage type is presented here. 2D
      deconvolution of the HSQC spectra facilitated accurate integration of all
      anomeric cross-peaks. Analysis of the differences in the integrals led to the
      proposal that C. albicans serotype B hyphal mannan side chains have the shortened
      structural moieties: Manalpha1-2Manalpha1- and Manalpha1-3 [Manalpha1-6]
      Manalpha1-2Manalpha1-. These represent the dominant structures important for
      construction of a saccharide-based prospective anti-candida vaccine.

PMID- 29654476
TI  - Tracking arousal state and mind wandering with pupillometry.
AB  - In four experiments, the association between arousal state and different mind
      wandering states was examined. Participants performed a sustained attention task
      while pupil responses were continuously recorded. Periodically during the task,
      participants were presented with thought probes to determine if they were on task
      or mind wandering. Across the four experiments, the results suggested that in
      situations that promoted on-task behaviors and focused external attention, mind
      wandering was associated with lowered arousal, as seen by smaller tonic pupil
      diameters and smaller phasic pupillary responses. However, in situations that
      promoted a more internal focus of attention, there were no differences between on
      task states and mind wandering in tonic pupil diameter (although differences
      emerged for phasic pupillary responses), suggesting similar arousal levels.
      Furthermore, across the four experiments, mind blanking and mind wandering
      dissociated in terms of whether the situation promoted focused external attention
      or focused internal attention. These results are broadly consistent with the
      notion that mind wandering is a heterogeneous construct, with different forms of
      mind wandering being associated with different arousal states, and suggest that a
      combination of behavioral and pupillary measures can be used to track these
      various states.

PMID- 29654478
TI  - Using ERPs to explore the impact of affective distraction on working memory
      stages in schizophrenia.
AB  - Research on individuals with schizophrenia (SCZ) shows a variety of emotional and
      cognitive deficits. We examined the hypothesis that ineffective emotional
      interference control may impact working memory (WM) performance by disrupting
      information encoding, maintenance, or retrieval in SCZ. Twenty-eight SCZ and 28
      matched healthy controls (HC) performed the visual and verbal delayed-matching-to
      sample task (DMST) with trials preceded by negative and nonemotional visual
      distractors. Event-Related Potentials associated with affective stimuli
      processing (Late Positive Potential-LPP) and WM-encoding (target-P3), maintenance
      (Negative Slow Wave-NSW), and retrieval (probe-P3) were analyzed. Patients showed
      overall worse DMST accuracy than HC. Emotional distraction negatively impacted
      accuracy during the verbal DMST in both groups combined. Both groups also
      displayed similar LPP modulation during the presentation of emotional
      distractors. HC showed enhanced NSW after presentation of a negative distraction,
      whereas this did not occur in SCZ. Comparable effects of emotional distraction
      were found for WM-encoding and retrieval in both groups. While emotional and
      neutral stimuli differentially impacted WM-maintenance on the neural level in HC,
      we did not observe this effect in SCZ, even though both groups showed similar
      behavioral and neurophysiological reactions to affective stimuli. Deficits in
      inhibitory mechanisms in SCZ may be responsible for this effect and may have
      particular relevance for WM-maintenance difficulties.

PMID- 29654477
TI  - Monitor yourself! Deficient error-related brain activity predicts real-life self
      control failures.
AB  - Despite their immense relevance, the neurocognitive mechanisms underlying real
      life self-control failures (SCFs) are insufficiently understood. Whereas previous
      studies have shown that SCFs were associated with decreased activity in the right
      inferior frontal gyrus (rIFG; a region involved in cognitive control), here we
      consider the possibility that the reduced implementation of cognitive control in
      individuals with low self-control may be due to impaired performance monitoring.
      Following a brain-as-predictor approach, we combined experience sampling of daily
      SCFs with functional magnetic resonance imaging (fMRI) in a Stroop task. In our
      sample of 118 participants, proneness to SCF was reliably predicted by low error
      related activation of a performance-monitoring network (comprising anterior mid
      cingulate cortex, presupplementary motor area, and anterior insula), low
      posterror rIFG activation, and reduced posterror slowing. Remarkably, these
      neural and behavioral measures predicted variability in SCFs beyond what was
      predicted by self-reported trait self-control. These results suggest that real
      life SCFs may result from deficient performance monitoring, leading to reduced
      recruitment of cognitive control after responses that conflict with superordinate
      goals.

PMID- 29654479
TI  - Monitoring of patients treated with lithium for bipolar disorder: an
      international survey.
AB  - BACKGROUND: Adequate monitoring of patients using lithium is needed for optimal
      dosing and for early identification of patients with (potential) ADEs. The
      objective was to internationally assess how health care professionals monitor
      patients treated with lithium for bipolar disorder. METHODS: Using networks of
      various professional organizations, an anonymous online survey was conducted
      among health care professionals prescribing lithium. Target lithium serum levels
      and frequency of monitoring was assessed together with monitoring of physical and
      laboratory parameters. Reasons to and not to monitor and use of guidelines and
      institutional protocols, and local monitoring systems were investigated. RESULTS:
      The survey was completed by 117 health care professionals incorporating responses
      from twenty-four countries. All prescribers reported to monitor lithium serum
      levels on a regular basis, with varying target ranges. Almost all (> 97%)
      monitored thyroid and renal function before start and during maintenance
      treatment. Reported monitoring of other laboratory and physical parameters was
      variable. The majority of respondents (74%) used guidelines or institutional
      protocols for monitoring. In general, the prescriber was responsible for
      monitoring, had to request every monitoring parameter separately and only a
      minority of patients was automatically invited. CONCLUSIONS: Lithium serum
      levels, renal and thyroid function were monitored by (almost) all physicians.
      However, there was considerable variation in other monitoring parameters. Our
      results help to understand why prescribers of lithium monitor patients and what
      their main reasons are not to monitor patients using lithium.

PMID- 29654480
TI  - Optimizing right ventricular focused four-chamber views using three-dimensional
      imaging, a comparative magnetic resonance based study.
AB  - Obtaining focused right ventricular (RV) apical view remains challenging using
      conventional two-dimensional (2D) echocardiography. This study main objective was
      to determine whether measurements from RV focused views derived from three
      dimensional (3D) echocardiography (3D-RV-focused) are closely related to
      measurements from magnetic resonance (CMR). A first cohort of 47 patients
      underwent 3D echocardiography and CMR imaging within 2 h of each other. A second
      cohort of 25 patients had repeat 3D echocardiography to determine the test-retest
      characteristics; and evaluate the bias associated with unfocused RV views.
      Tomographic views were extracted from the 3D dataset: RV focused views were
      obtained using the maximal RV diameter in the transverse plane, and unfocused
      views from a smaller transverse diameter enabling visualization of the tricuspid
      valve opening. Measures derived using the 3D-RV-focused view were strongly
      associated with CMR measurements. Among functional metrics, the strongest
      association was between RV fractional area change (RVFAC) and ejection fraction
      (RVEF) (r = 0.92) while tricuspid annular plane systolic excursion moderately
      correlated with RVEF (r = 0.47), all p < 0.001. Among RV size measures, the
      strongest association was found between RV end-systolic area (RVESA) and volume
      (r = 0.87, p < 0.001). RV unfocused views led on average to 10% underestimation
      of RVESA. The 3D-RV-focused method had acceptable test-retest characteristics
      with a coefficient of variation of 10% for RVESA and 11% for RVFAC. Deriving
      standardized RV focused views using 3D echocardiography strongly relates to CMR
      derived measures and may improve reproducibility in RV 2D measurements.

PMID- 29654481
TI  - Analysis of anomalous origin of coronary arteries by coronary angiography in
      Chinese patients with coronary artery disease.
AB  - With the development of coronary angiography for the diagnosis of coronary artery
      disease, its clinical significance in detecting coronary artery anomalies and
      evaluating the seriousness is attracting more attention. In the study we aimed to
      assess the prevalence of anomalous origin of coronary arteries in a Chinese
      population who underwent coronary angiography for coronary artery disease, and
      explore any patterns in the common variants and typical anomalies, especially the
      potentially serious ones. Patients who underwent coronary angiography from
      January 2013 to December 2016 in Fuwai Hospital were included. Baseline
      characteristics and angiographic data were collected, the incidence of anomalous
      origin of coronary arteries was calculated, and the typical patterns were
      analyzed. Comparisons between the present results and those of existing reports
      were also conducted. A total of 110,158 patients were included in the study,
      among which 0.76% (835 cases) had anomalous origin of coronary arteries. Among
      the anomalies, the incidences of anomalous origin of the right coronary artery
      (RCA), the left coronary artery (LCA), both the RCA and LCA, single coronary
      artery (SCA) and dextrocardia were 76.76% (641 cases), 14.61% (122 cases), 1.80%
      (15 cases), 4.67% (39 cases) and 2.16% (18 cases), respectively. Moreover, 47.54%
      (397 cases) of the anomalies were shown to be potentially serious, and an RCA
      arising from the left sinus of Valsalva (LSV) was the most common subtype
      (39.28%, 328 cases). Although anomalous origin of coronary arteries is not quite
      common, more clinical attention should be paid to this condition due to the
      potential risk of serious sequelae.

PMID- 29654482
TI  - Fear, foraging and olfaction: how mesopredators avoid costly interactions with
      apex predators.
AB  - Where direct killing is rare and niche overlap low, sympatric carnivores may
      appear to coexist without conflict. Interference interactions, harassment and
      injury from larger carnivores may still pose a risk to smaller mesopredators.
      Foraging theory suggests that animals should adjust their behaviour accordingly
      to optimise foraging efficiency and overall fitness, trading off harvest rate
      with costs to fitness. The foraging behaviour of red foxes, Vulpes vulpes, was
      studied with automated cameras and a repeated measures giving-up density (GUD)
      experiment where olfactory risk cues were manipulated. In Plitvice Lakes National
      Park, Croatia, red foxes increased GUDs by 34% and quitting harvest rates by 29%
      in response to wolf urine. In addition to leaving more food behind, foxes also
      responded to wolf urine by spending less time visiting food patches each day and
      altering their behaviour in order to compensate for the increased risk when
      foraging from patches. Thus, red foxes utilised olfaction to assess risk and
      experienced foraging costs due to the presence of a cue from gray wolves, Canis
      lupus. This study identifies behavioural mechanisms which may enable competing
      predators to coexist, and highlights the potential for additional ecosystem
      service pathways arising from the behaviour of large carnivores. Given the
      vulnerability of large carnivores to anthropogenic disturbance, a growing human
      population and intensifying resource consumption, it becomes increasingly
      important to understand ecological processes so that land can be managed
      appropriately.

PMID- 29654483
TI  - Chinese Experts Consensus on Clinical Application of Naoxintong Capsule ().

PMID- 29654484
TI  - Investigation on Physicochemical Characteristics of a Nanoliposome-Based System
      for Dual Drug Delivery.
AB  - Synergistic effects of multiple drugs with different modes of action are utilized
      for combinatorial chemotherapy of intractable cancers. Translation of in vitro
      synergistic effects into the clinic can be realized using an efficient delivery
      system of the drugs. Despite a few studies on nano-sized liposomes containing
      erlotinib (ERL) and doxorubicin (DOX) in a single liposome vesicle, reliable and
      reproducible preparation methods as well as physicochemical characteristics of a
      non-PEGylated nanoliposome co-encapsulated with ERL and DOX have not been yet
      elucidated. In this study, ERL-encapsulated nanoliposomes were prepared using the
      lipid film-hydration method. By ultrasonication using a probe sonicator, the
      liposome diameter was reduced to less than 200 nm. DOX was loaded into the ERL
      encapsulated nanoliposomes using ammonium sulfate (AS)-gradient or pH-gradient
      method. Effects of DOX-loading conditions on encapsulation efficiency (EE) of the
      DOX were investigated to determine an efficient drug-loading method. In the EE of
      DOX, AS-gradient method was more effective than pH gradient. The dual drug
      encapsulated nanoliposomes had more than 90% EE of DOX and 30% EE of ERL,
      respectively. Transmission electron microscopy and selected area electron
      diffraction analyses of the dual drug-encapsulated nanoliposomes verified the
      highly oriented DOX-sulfate crystals inside the liposome as well as the less
      oriented small crystals of ERL in the outermost region of the nanoliposome. The
      nanoliposomes were stable at different temperatures without an increase of the
      nanoliposome diameter. The dual drug-encapsulated nanoliposomes showed a time
      differential release of ERL and DOX, implying proper sequential releases for
      their synergism. The preparation methods and the physicochemical characteristics
      of the dual drug delivery system contribute to the development of the optimal
      process and more advanced systems for translational researches.

PMID- 29654485
TI  - Long-term, interventional, open-label extension study evaluating the safety of
      tocilizumab treatment in patients with polyarticular-course juvenile idiopathic
      arthritis from Poland and Russia who completed the global, international CHERISH
      trial.
AB  - Efficacy and safety of tocilizumab (TCZ), an interleukin-6 receptor inhibitor,
      were demonstrated in juvenile idiopathic arthritis (JIA) with polyarticular
      course (pJIA) in the CHERISH trial. This observational, III phase study evaluated
      long-term treatment of TCZ in pJIA patients was conducted by members of the
      Pediatric Rheumatology International Trials Organization (PRINTO) from Poland and
      Russia. Forty-one patients, who had completed the CHERISH core study (104 weeks),
      were extensionally treated with TCZ (8 mg/kg, intravenous infusion every 4
      weeks). Total treatment time was from 131 to 193 weeks. The long-term safety (the
      primary endpoint) and efficacy were evaluated. All patients achieved ACR70
      response in the core study and continued to achieve at least ACR50 response up to
      week 24 of this study. The safety population comprised 46.41 patient-years (PY).
      Rates per 100 PY of adverse (AEs) and serious events (SAEs) were 181.0 and 6.46,
      respectively. Pharyngitis and respiratory tract infections were the most common
      AEs. Except one AE (severe neutropenia), all others were classified as mild
      (24.4%) or moderate (29.3%). The incidence of SAEs was low (7.3%). No new safety
      findings were observed. The safety profile of over 2.5-year treatment with TCZ is
      consistent with the pre-marketing CHERISH clinical trial. Presented data and
      continued efficacy response support the use of TCZ in pJIA. EUDRACT No: 2011
      001607-12. https://clinicaltrials.gov/ct2/show/study/NCT01575769?term=ML27783.

PMID- 29654487
TI  - Metal Contents in the Most Widely Consumed Commercial Preparations of Four
      Different Medicinal Plants (Aloe, Senna, Ginseng, and Ginkgo) from Europe.
AB  - Medicinal plants like Aloe barbadensis, Ginkgo biloba, Panax ginseng, and Cassia
      angustifolia are being increasingly used but self-medication is a major public
      health challenge because of their numerous interactions. Furthermore, dietary
      exposure to metals through the consumption of these commercial preparations
      should be evaluated. Some of these metals may have a nutritional interest but
      others are metals of toxicological relevance. The content of essential and toxic
      metals has been analyzed by inductively coupled plasma optical emission
      spectrometry (ICP-OES) in 80 samples of both organically and conventionally grown
      aloe, senna, ginseng, and ginkgo pharmaceutical formats to establish their
      metallic profile, to evaluate their nutritional value and to assess the toxic
      metal risk resulting from their consumption. Ca (9181 mg/kg ww) in senna, Fe
      (30.0 mg/kg ww) in ginseng, and Al (15.7 mg/kg ww) in ginseng are noteworthy. The
      consumption of 9 g/day of ginkgo represents 6.44% of the RDI set for Ca. The
      consumption of 25 mL/day of aloe syrup is 3.06% (men) and 1.52% (women) of the
      RDI of Fe. Al exposure from 25 mL/day of aloe consumption is 2.71% of its TDI.
      Considering the dosages recommended by the manufacturers, the intake of toxic
      metals does not pose a health risk but the intake of essential metals is worth
      mentioning.

PMID- 29654486
TI  - Variation in pain related to systemic lupus erythematosus (SLE): a 7-year follow
      up study.
AB  - We have previously shown that most patients with systemic lupus erythematosus
      (SLE) reported low degree of SLE-related pain. However, 24% of the patients
      reported high degree of SLE-related pain, more fatigue, anxiety and depression,
      and worse health-related quality of life (HRQoL). To explore SLE-related pain,
      the presence of long-standing widespread pain, and patient-reported outcomes
      (PROs) after 7 years. Sixty-four out of 84 patients participated in a 7-year
      follow-up of the original survey and completed the same questionnaires answered
      at inclusion: pain (VAS 100 mm), fatigue (MAF), HRQoL (SF-36), anxiety and
      depression (HADS), and, if appropriate, a pain-drawing. Differences between
      inclusion and follow-up (change) were calculated. The patients with a low degree
      of SLE-related pain at inclusion reported no changes at follow-up in pain and
      PROs except for worsening in physical function in SF-36, median change (IQR) 0 (-
      10 to 5), p = 0.024. Half of the patients with high degree of pain at inclusion
      reported decreased pain at follow-up, median change (IQR) 45 (35 to 65), p =
      0.021; fatigue, 8 (8 to 17), p = 0.018; anxiety, 4 (1 to 4), p = 0.035; and
      depression, 4 (2 to 5), p = 0.018 and improvements in most dimensions of SF-36.
      The remaining half of the patients reported no changes regarding pain and PROs
      except for a worsening in vitality in SF-36, 20 (15 to 35), p = 0.0018. All
      patients with remaining high level of pain indicated long-standing widespread
      pain. After 7 years, a subgroup of patients with SLE reported remaining high
      level of SLE-related pain and a high symptom burden, including long-standing
      widespread pain. Such patients require more observant attention to receive
      appropriate treatment.

PMID- 29654488
TI  - Impact of the Di(2-Ethylhexyl) Phthalate Administration on Trace Element and
      Mineral Levels in Relation of Kidney and Liver Damage in Rats.
AB  - Di(2-ethylhexyl) phthalate (DEHP) is a widely used synthetic polymer in the
      industry. DEHP may induce reproductive and developmental toxicity, obesity,
      carcinogenesis and cause abnormal endocrine function in both human and wildlife.
      The aim of this study was to investigate trace element and mineral levels in
      relation of kidney and liver damage in DEHP-administered rats. Therefore,
      prepubertal male rats were dosed with 0, 100, 200, and 400 mg/kg/day of DEHP. At
      the end of the experiment, trace element and mineral levels, glucose-6-phosphate
      dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6-PGD), glutathione
      reductase (GR) and glutathione S-transferase (GST) enzyme activities were
      evaluated in the serum, liver, and kidney samples of rats. Furthermore, serum
      clinical biochemistry parameters, organ/body weight ratios and histological
      changes were investigated to evaluate impact of DEHP more detailed. Our data
      indicated that sodium (Na), calcium (Ca), potassium (K), lithium (Li), rubidium
      (Rb) and cesium (Cs) levels significantly decreased, however iron (Fe) and
      selenium (Se) concentrations significantly increased in DEHP-administered groups
      compared to the control in the serum samples. On the other hand, upon DEHP
      administration, selenium concentration, G6PD and GR activities were significantly
      elevated, however 6-PGD activity significantly decreased compared to the control
      group in the kidney samples. Decreased G6PD activity was the only significant
      change between anti-oxidant enzyme activities in the liver samples. Upon DEHP
      administration, aberrant serum biochemical parameters have arisen and abnormal
      histological changes were observed in the kidney and liver tissue. In conclusion,
      DEHP may induce liver and kidney damage, also result abnormalities in the trace
      element and mineral levels.

PMID- 29654489
TI  - Boron Content of Some Foods Consumed in Istanbul, Turkey.
AB  - The boron content was determined in 42 different foods consumed in Istanbul,
      Turkey. Eleven species of fruit, ten species of vegetable, eight species of food
      of animal origin, four species of grain, two species of nuts, two species of
      legume, and five other kinds of foods were included to this study. They were
      analyzed by two methods: Inductively coupled plasma mass spectrometry (ICP-MS)
      technique and carminic acid assay, and the results of two methods were also
      compared. Boron concentration in foods ranged between 0.06-37.2 mg/kg. Nuts had
      the highest boron content while foods of animal origin had the lowest. A strong
      correlation was found between the results of the carminic acid assay and the ICP
      MS technique (p = 0.0001, Pearson correlation coefficient: r = 0.956). Bland
      Altman analysis also supported this correlation. ICP-MS is one of the most
      common, reliable, and powerful method for boron determination. The results of our
      study show that spectrophotometric carminic acid assay can provide similar
      results to ICP-MS, and the boron content in food materials can be also determined
      by spectrophotometric method.

PMID- 29654490
TI  - Long-Term, Fructose-Induced Metabolic Syndrome-Like Condition Is Associated with
      Higher Metabolism, Reduced Synaptic Plasticity and Cognitive Impairment in
      Octodon degus.
AB  - There has been a progressive increase in the incidence of fructose-induced
      metabolic disorders, such as metabolic syndrome (MetS). Moreover, novel evidence
      reported negative effects of high-fructose diets in brain function. This study
      was designed to evaluate for the first time the effects of long-term fructose
      consumption (LT-FC) on the normal ageing process in a long-lived animal model
      rodent, Octodon degus or degu. Moreover, we could replicate human sugar
      consumption behaviour over time, leading us to understand then the possible
      mechanisms by which this MetS-like condition could affect cognitive abilities.
      Our results support that 28 months (from pup to adulthood) of a 15% solution of
      fructose induced clinical conditions similar to MetS which includes an insulin
      resistance scenario together with elevated basal metabolic rate and non-alcoholic
      fatty liver disease. Additionally, we extended our analysis to evaluate the
      impact of this MetS-like condition on the functional and cognitive brain
      processes. Behavioural test suggests that fructose-induced MetS-like condition
      impair hippocampal-dependent and independent memory performance. Moreover, we
      also reported several neuropathological events as impaired hippocampal redox
      balance, together with synaptic protein loss. These changes might be responsible
      for the alterations in synaptic plasticity and transmitter release observed in
      these cognitively impaired animals. Our results indicate that LT-FC induced
      several facets of MetS that eventually could trigger brain disorders, in
      particular, synaptic dysfunction and reduced cognition.

PMID- 29654491
TI  - SIRT2 Inhibition Confers Neuroprotection by Downregulation of FOXO3a and MAPK
      Signaling Pathways in Ischemic Stroke.
AB  - Sirtuin 2 (SIRT2) is a family member of nicotinamide adenine dinucleotide (NAD+)
      dependent deacetylases which appears to have detrimental roles in an array of
      neurological disorders such as Parkinson's disease (PD) and Huntington's disease
      (HD). In light of the recently emerging roles of sirtuins in normal physiology
      and pathological conditions such as ischemic stroke, we investigated the role of
      SIRT2 in ischemic stroke-induced neuronal cell death. Primary cortical neurons
      were subjected to oxygen-glucose deprivation (OGD) under in vitro ischemic
      conditions, and subsequently tested for the efficacy of SIRT2 inhibitors AK1 and
      AGK2 in attenuating apoptotic cell death caused by OGD. We have also evaluated
      the effect of SIRT2 inhibition in C57BL/6 mice subjected to 1 h middle cerebral
      artery occlusion (MCAO) followed by 24 h reperfusion, which is a model for
      ischemic reperfusion injury in vivo. Significant reductions in apoptotic cell
      death were noted in neurons treated with AK1 or AGK2, as evidenced by reduced
      cleaved caspase-3 and other apoptotic markers such as Bim and Bad. In addition,
      downregulation of phosphorylated-AKT and FOXO3a proteins of the AKT/FOXO3a
      pathway, as well as a marked reduction of JNK activity and its downstream target
      c-Jun, were also observed. When tested in animals subjected to MCAO, the
      neuroprotective effects of AGK2 in vivo were evidenced by a substantial reduction
      in ipsilateral infarct area and a significant improvement in neurological
      outcomes. A similar reduction in the levels of pro-apoptotic proteins in the
      infarct tissue, as well as downregulation of AKT/FOXO3a and JNK pathway, were
      also noted. In summary, the current study demonstrated the neuroprotective
      effects of SIRT2 inhibition in ischemic stroke, and identified the downregulation
      of AKT/FOXO3a and MAPK pathways as intermediary mechanisms which may contribute
      to the reduction in apoptotic cell death by SIRT2 inhibition.

PMID- 29654492
TI  - Polymorphic Expression of UGT1A9 is Associated with Variable Acetaminophen
      Glucuronidation in Neonates: A Population Pharmacokinetic and Pharmacogenetic
      Study.
AB  - INTRODUCTION: Acetaminophen (paracetamol, APAP) is widely used as an analgesic
      and antipyretic drug in children and neonates. A number of enzymes contribute to
      the metabolism of acetaminophen, and genetic factors might be important to
      explain variability in acetaminophen metabolism among individuals. METHODS: The
      current investigation utilized a previously published parent-metabolite
      population pharmacokinetic model describing acetaminophen glucuronidation,
      sulfation, and oxidation to examine the potential role of genetic variability on
      the relevant metabolic pathways. Neonates were administered 30-min intravenous
      infusions of acetaminophen 15 mg/kg every 12 h (< 28 weeks' gestational age [GA])
      or every 8 h (>= 28 weeks GA) for 48 h. A total of 18 sequence variations (SVs)
      in UDP-glucuronosyltransferase (UGT), sulfotransferase (SULT), and cytochrome
      P450 (CYP) genes from 33 neonates (aged 1-26 days) were examined in a stepwise
      manner for an effect on the metabolic formation clearance of acetaminophen by
      glucuronidation (UGT), sulfation (SULT), and oxidation (CYP). The stepwise
      covariate modeling procedure was performed using NONMEM(r) version 7.3. RESULTS:
      Incorporation of genotype as a covariate for one SV located in the UGT1A9 gene
      promoter region (rs3832043, - 118 > insT, T9 > T10) significantly improved model
      fit (likelihood ratio test, p < 0.001) and reduced between-subject variability in
      glucuronide formation clearance. Individuals with the UGT1A9 T10 polymorphism,
      indicating insertion of an additional thymidine nucleotide, had a 42% reduction
      in clearance to APAP-glucuronide as compared to their wild-type counterparts.
      CONCLUSION: This study shows a pharmacogenetic effect of an SV in the UGT1A9
      promoter region on the metabolism of acetaminophen in neonates.

PMID- 29654493
TI  - Yellow-Cedar, Callitropsis (Chamaecyparis) nootkatensis, Secondary Metabolites,
      Biological Activities, and Chemical Ecology.
AB  - Yellow-cedar, Callitropsis nootkatensis, is prevalent in coastal forests of
      southeast Alaska, western Canada, and inland forests along the Cascades to
      northern California, USA. These trees have few microbial or animal pests,
      attributable in part to the distinct groups of biologically active secondary
      metabolites their tissues store for chemical defense. Here we summarize the new
      yellow-cedar compounds identified and their biological activities, plus new or
      expanded activities for tissues, extracts, essential oils and previously known
      compounds since the last review more than 40 years ago. Monoterpene hydrocarbons
      are the most abundant compounds in foliage, while heartwood contains substantial
      quantities of oxygenated monoterpenes and oxygenated sesquiterpenes, with one or
      more tropolones. Diterpenes occur in foliage and bark, whereas condensed tannins
      have been isolated from inner bark. Biological activities expressed by one or
      more compounds in these groups include fungicide, bactericide, sporicide,
      acaricide, insecticide, general cytotoxicity, antioxidant and human anticancer.
      The diversity of organisms impacted by whole tissues, essential oils, extracts,
      or individual compounds now encompasses ticks, fleas, termites, ants, mosquitoes,
      bacteria, a water mold, fungi and browsing animals. Nootkatone, is a heartwood
      component with sufficient activity against arthropods to warrant research focused
      toward potential development as a commercial repellent and biopesticide for
      ticks, mosquitoes and possibly other arthropods that vector human and animal
      pathogens.

PMID- 29654494
TI  - Microwave-assisted synthesis of carbon dots for "turn-on" fluorometric
      determination of Hg(II) via aggregation-induced emission.
AB  - A fluorescent probe is presented for sensitive determination of Hg(II). It is
      based on aggregation induced enhancement effect (AIEE) of carbon dots co-doped
      with nitrogen and sulfur (N,S-CDs). The N,S-CDs were prepared by a one-pot
      microwave-assisted method using glycerol as the reaction solvent, and cystine as
      the source for C, N and S. The resulting CDs are well soluble in water and have a
      turn-on fluorescence response to Hg(II). The incubation time and ratio of raw
      materials were optimized. Fluorescence, best measured at excitation/emission
      wavelengths of 325/385 nm, increases linearly in the 1-75 MUM Hg(II)
      concentration range, and the detection limit is 0.5 MUM. The method performed
      successfully when detecting Hg(II) in spiked tap and lake waters, with recoveries
      between 92 and 106%. Graphical abstract Schematic presentation of the aggregation
      induced enhancement of the fluorescence of carbon dots co-doped with nitrogen and
      sulfur after addition of Hg(II).

PMID- 29654495
TI  - [Physiological changes during pregnancy].
AB  - The physiological state of a woman experiences multiple changes in the body
      during pregnancy. These alterations could be of particular importance in the
      medical care of pregnant women. This review article highlights the physiological
      developments of various organ systems throughout gestation with a focus on
      endocrinology, the cardiovascular system, hematology, the respiratory system and
      water balance.

PMID- 29654496
TI  - Evaluation of candidemia and antifungal consumption in a large tertiary care
      Italian hospital over a 12-year period.
AB  - PURPOSE: An early adequate antifungal therapy based on the knowledge of local
      epidemiology can reduce the candidemia-attributable mortality and the length of
      hospitalization. We performed a retrospective study to analyze the epidemiology
      of candidemia and the antifungal consumption in our hospital. METHODS: We
      analyzed Candida spp. isolated from the blood, and their susceptibility profile
      from 2005 to 2016 in Careggi University Hospital, Florence, Italy. We also
      performed a stratified analysis by clinical setting where Candida spp. were
      isolated (Medical Wards, Surgery, Intensive Care Unit-ICU). Then, we
      retrospectively reviewed the annual consumption of antifungal agents and
      calculated the defined daily dosing for 10,000 hospital days. RESULTS: The rate
      of candidemia was higher in ICU than other settings and Candida albicans was the
      first cause of candidemia (61.2%). After adjustment for hospital days, the rate
      of C. albicans showed a statistically significant parabolic trend (p < 0.001),
      with a peak of incidence in 2010. After 2010, we observed a reduction of
      candidemia due to both C. albicans and non-albicans species. Between 2005 and
      2015, we reported an increasing increased use of echinocandins. As far as
      resistance profile is concerned, only one Candida glabrata isolate was resistant
      to caspofungin (1.9%) and 30% of C. glabrata were resistant to fluconazole.
      CONCLUSIONS: Our data describe C. albicans as the first cause of candidemia in
      all the studied settings and the low rate of echinocandin resistance, despite
      their increased use over the study period. ICU was confirmed as the setting with
      the highest incidence of candidemia.

PMID- 29654497
TI  - From Ignac Semmelweis to Primary Immunodeficiencies: a Bicentenary Commemoration.

PMID- 29654498
TI  - Comparative effect of coffee robusta and coffee arabica (Qahwa) on memory and
      attention.
AB  - The comparative effects of coffee robusta and coffee arabica (Qahwa) on different
      attention and memory related assignments were measured in a double-blind study of
      300 healthy young adult women who were randomly assigned to one of three
      different drinks: Group I (coffee robusta sachet dissolved in 100 ml of hot
      water): Group II (coffee arabica): and group III (100 ml water only). Cognitive
      function was assessed by standardized tests. Several monitoring cognitive tests
      and tasks were specifically chosen and performed to investigate the comparative
      effects of coffee robusta (CR) and coffee arabica (Qahwa; AC) on sleepiness
      (sleep and clear headed scale), attention (trail A & B, symbol digit, letter
      cancellation), general cognitive ability (stroop test) and memory (card test).
      Data was interpreted by analysis of variance (ANOVA). The present study revealed
      that coffee robusta has beneficial effects on attention, general cognitive
      ability and memory. Higher though non-significant cognitive scores were
      associated with coffee robusta consumption. Although, consumption of coffee
      arabica (Qahwa) has significant effects (P < 0.05) on sleepiness, attention,
      general cognitive ability and memory and it significantly improve reaction time
      and correct responses. Since different tasks were related to the sustained
      attention and working memory processes, results would suggest that coffee arabica
      (qahwa) could increase the memory and efficiency of the attentional system might
      be due to the presence of chlorogenic acids (CGA) which are found in less
      quantity in coffee robusta. However, more studies using larger samples and
      different tasks are necessary to better understand the effects of coffee robusta
      and arabica (Qahwa) on attention and memory.

PMID- 29654501
TI  - Growth performance, economic benefits and sensory characteristics of meat from
      broilers finished on Acacia anguistissima leaf meal-based diets.
AB  - The objective of the study was to determine growth performance, viscera organ
      development, economic benefit and sensory characteristics of meat from broilers
      finished on Acacia anguistissima leaf meal-based diets. One hundred and eighty
      Cobb 500-day-old chicks were used in the study. Acacia anguistissima was used as
      a protein source and included in broiler diets at 0, 50 and 100 g/kg. Total feed
      intake (TFI), average daily gain (ADG), and gain to feed ratio (G:F) and cost
      benefit analysis were determined. There were no differences in TFI of broilers
      across treatments diets. Average daily gain and gain to feed (G:F) ratio were low
      (P < 0.05) for broilers feeding on diet with100 g/kg acacia meal. Highest returns
      from weight gain were obtained from broiler chickens fed on diet with 50 g/kg
      inclusion level of A. anguistissima (P < 0.05). Intestinal length increased with
      inclusion level of A. anguistissima whereas liver and spleen weight decreased
      with inclusion level of A. anguistissima (P < 0.05). Female consumers gave higher
      scores for overall flavour intensity than male consumers (P < 0.05). Treatment
      diets influenced consumer sensory characteristics of broiler meat (P < 0.05).
      High sensory scores were observed for overall flavour intensity (OFI) for both
      boiled and deep fried meat from broilers fed 100 g/kg A. anguistissima. It can be
      concluded that A. anguistissima meal can be used effectively up to 50 g/kg in
      broiler diets without compromising performance of chickens and can influence a
      few sensory characteristics.

PMID- 29654500
TI  - Influence of Nigella sativa seeds, Rosmarinus officinalis leaves and their
      combination on growth performance, immune response and rumen metabolism in Dorper
      lambs.
AB  - The objective of this study was to determine the effects of dietary
      supplementation of Nigella sativa L. seeds, Rosmarinus officinalis L. leaves and
      their combination on rumen metabolism, nutrient intake and digestibility, growth
      performance, immune response and blood metabolites in Dorper lambs. Twenty-four
      entire male Dorper lambs (18.68 +/- 0.6 kg, 4-5 months old) were randomly
      assigned to a concentrate mixture containing on a dry matter basis either, no
      supplement (control, T1), 1% R. officinalis leaves (T2), 1% N. sativa seeds (T3)
      or 1% R. officinalis leaves +1% N. sativa seeds (T4). The lambs had ad libitum
      access to urea-treated rice straw (UTRS) and were raised for 90 days.
      Supplemented lambs had greater (P < 0.05) intake of DM and UTRS than the control
      lambs. The T4 lambs had lower (P < 0.05) nutrient digestibility than those fed
      other treatments. Total and daily weight gain was greater (P < 0.05) in T2 lambs
      than those fed other diets. The T3 and T4 lambs had greater (P < 0.05) ruminal pH
      than the T1 and T2 lambs. Supplemented lambs had lower (P < 0.05) ruminal total
      volatile fatty acids, acetate, propionate, NH3-N and C18:0 than the control
      lambs. The T4 lambs had lower (P < 0.05) population of Fibrobacter succinogenes,
      Ruminococcus albus, methanogens and total protozoa compared with those fed other
      diets. Supplemented lambs had lower (P < 0.05) neutrophils, basophils and serum
      urea and greater (P < 0.05) serum IgA and IgG compared with the control lambs.
      The current results emphasised the variation in the efficacy of medicinal plants
      in ruminant nutrition.

PMID- 29654499
TI  - Cortical and subcortical gray matter structural alterations in normoglycemic
      obese and type 2 diabetes patients: relationship with adiposity, glucose, and
      insulin.
AB  - Type 2 diabetes (T2DM) is associated with structural cortical and subcortical
      alterations, although it is insufficiently clear if these alterations are driven
      by obesity or by diabetes and its associated complications. We used FreeSurfer5.3
      and FSL-FIRST to determine cortical thickness, volume and surface area, and
      subcortical gray matter volume in a group of 16 normoglycemic obese subjects and
      28 obese T2DM patients without clinically manifest micro- and marcoangiopathy,
      and compared them to 31 lean normoglycemic controls. Forward regression analysis
      was used to determine demographic and clinical correlates of altered
      (sub)cortical structure. Exploratively, vertex-wise correlations between cortical
      structure and fasting glucose and insulin were calculated. Compared with
      controls, obese T2DM patients showed lower right insula thickness and lower left
      lateral occipital surface area (PFWE < 0.05). Normoglycemic obese versus controls
      had lower thickness (PFWE < 0.05) in the right insula and inferior frontal gyrus,
      and higher amygdala and thalamus volume. Thalamus volume and left paracentral
      surface area were also higher in this group compared with obese T2DM patients.
      Age, sex, BMI, fasting glucose, and cholesterol were related to these
      (sub)cortical alterations in the whole group (all P < 0.05). Insulin were related
      to temporal and frontal structural deficits (all PFWE < 0.05). Parietal/occipital
      structural deficits may constitute early T2DM-related cerebral alterations,
      whereas in normoglycemic obese subjects, regions involved in emotion, appetite,
      satiety regulation, and inhibition were affected. Central adiposity and elevated
      fasting glucose may constitute risk factors.

PMID- 29654502
TI  - Effects of replacing fishmeal with black soldier fly larval meal in the diets of
      grower-finishing guinea fowls reared under tropical conditions.
AB  - The study was conducted with the view to determine the impact of replacing
      fishmeal with black soldier fly larval meal (BSFLM) on growing guinea fowls.
      BSFLM replaced fishmeal (3% in the control diet) in the ratios of 0, 20, 40, 60,
      80, and 100% to produce six dietary treatments, which were iso-caloric and iso
      nitrogenous. Two hundred and forty-eight-week old guinea fowls with mean live
      weight of 273.2 +/- 10.9 g were tagged, weighted, and randomly assigned to 24 (6
      * 4) floor pens; each pen was treated as a replicate. Feed and water were
      provided ad libitum during the entire period, which lasted 10 weeks. Feed
      consumption differed among the treatment groups (P = 0.0072) with the 100%
      fishmeal diets recording the lowest. Daily gain was significantly (P = 0.009)
      higher for birds fed high BSFLM diets compared to the control (100% fishmeal
      diet). The inclusion of BSFLM in the diets elicited positive linear effect on
      weight gains of the guinea fowls (R2 = 0.91) with increasing concentration
      resulting in higher live weight gains. The feed conversion ratio (FCR) also
      differed between treatments (P < 0.05) but similar for the 100% fishmeal
      (control) and 100% BSFLM diets. Organ and haematopoitic integrity were equally
      assured regardless of levels of the protein sources fed to the birds. Generally,
      meats from birds fed 60 to 100% BSFLM and from hens were more acceptable. A study
      to evaluate the economics of utilising BSFLM in guinea fowl production is
      recommended.

PMID- 29654503
TI  - Relational Mindfulness for Psychiatry Residents: a Pilot Course in Empathy
      Development and Burnout Prevention.
AB  - OBJECTIVE: Psychiatry residents face challenges daily that test their capacity to
      be empathic and attuned to their own self-care. This can have a deleterious
      impact not only on the residents but also on patient-care. Training to manage the
      challenges of the work and cultivate stronger patient relationships is needed but
      often missing in medical education. This study aimed to pilot an empathy training
      course based in relational mindfulness and assess the impact on burnout and
      empathy. METHODS: Seven first-year psychiatry residents (PGY-1) at an academic
      medical center in a mid-size city in the southeast participated in an eight-week
      pilot program created by the authors that integrated relational mindfulness and
      empathy training. Data were gathered from the seven PGY-1s on measures of burnout
      and empathy and on their experience of the training. RESULTS: The PGY-1s
      demonstrated a downward trend in means on all three burnout subscales and
      significant improvement on the measure of empathy (f = 8.98; p = .02). Overall,
      the PGY-1s reported an increased awareness of their cognitive and emotional
      experiences and stated that the skills learned in the program increased their
      ability to care for themselves, their patients, and their families. CONCLUSIONS:
      Training in intrapersonal and interpersonal attunement is often overlooked in
      medical training, leading to resident burnout and negative patient outcomes. An
      empathy course based in relational mindfulness may be a viable strategy for
      programs looking to attend to their residents' emotional health and bridge the
      empathy training gap.

PMID- 29654505
TI  - Ionic liquid-based transmission electron microscopy for herpes simplex virus type
      1.

PMID- 29654506
TI  - Evaluating the Training of Chinese-Speaking Community Health Workers to Implement
      a Small-Group Intervention Promoting Mammography.
AB  - This study evaluated the training of Chinese American Community Health Workers
      (CHWs) to implement a small-group mammography video and discussion program as
      part of a randomized controlled trial that had the goal to increase adherence to
      mammography screening guidelines among Chinese American women. A total of 26
      Chinese American CHWs in the metropolitan Washington DC area, Southern
      California, and New York City participated in a 4-h training workshop and
      completed surveys before and after the workshop to assess their knowledge
      regarding mammography screening guidelines and human subjects protection rules.
      The results showed significantly increased knowledge of mammography screening
      guidelines and human subjects protection rules (both p < 0.01) after the
      training. CHWs were also trained to lead a discussion of the video, including
      screening benefits and misconceptions. Forty-three audio recordings of
      discussions led by 13 active CHWs were transcribed and qualitatively analyzed to
      assess implementation fidelity. Ten out of 13 active CHWs fully addressed about 3
      of the 5 benefit items, and 11 out of 13 CHWs fully addressed more than 5 of the
      9 misconception items. Chinese CHWs can be trained to implement research-based
      intervention programs. However, a one-time training resulted in moderate
      adherence to the discussion protocol. Ongoing or repeat trainings throughout the
      intervention period may be needed to enhance implementation fidelity.

PMID- 29654508
TI  - Another Case of Erratic Brain Embolism After Particle Embolization for a Giant
      Intrathoracic Solitary Fibrous Tumor.

PMID- 29654507
TI  - Response Assessment by Volumetric Iodine Uptake Measurement: Preliminary
      Experience in Patients with Intermediate-Advanced Hepatocellular Carcinoma
      Treated with Yttrium-90 Radioembolization.
AB  - PURPOSE: To retrospectively compare early response to yttrium-90
      radioembolization (Y90) according to volumetric iodine uptake (VIU) changes,
      Response Evaluation Criteria In Solid Tumor 1.1 (RECIST 1.1) and modified RECIST
      (mRECIST) in patients with intermediate-advanced hepatocellular carcinoma (HCC)
      and to explore their association with survival. MATERIALS AND METHODS: Twenty
      four patients treated with Y90 and evaluated with dual-energy computed tomography
      before and 6 weeks after treatment were included. VIU was measured on late
      arterial phase spectral images; 6-week VIU response was defined as: complete
      response (CR, absence of enhancing tumor), partial response (PR, >= 15% VIU
      reduction), progressive disease (PD, >= 10% VIU increase) and stable disease
      (criteria of CR/PR/PD not met). RECIST 1.1 and mRECIST were evaluated at 6 weeks
      and 6 months. Responders included CR and PR. Overall survival (OS) was evaluated
      by Kaplan-Meier analysis and compared by Cox regression analysis. RESULTS: High
      intraobserver and interobserver agreements were observed in VIU measurements (k >
      0.98). VIU identified a higher number of responders (18 patients, 75%), compared
      to RECIST 1.1 (12.5% at 6 weeks and 23.8% at 6 months) and mRECIST (29.2% at 6
      weeks and 61.9% at 6 months). There was no significant correlation between OS and
      RECIST 1.1 (P = 0.45 at 6 weeks; P = 0.21 at 6 months) or mRECIST (P = 0.38 at 6
      weeks; P = 0.79 at 6 months); median OS was significantly higher in VIU
      responders (17.2 months) compared to non-responders (7.4 months) (P = 0.0022; HR
      8.85; 95% CI 1.29-88.1). CONCLUSION: VIU is highly reproducible; as opposite to
      mRECIST and RECIST 1.1, early VIU response correlates with OS after Y90 in
      intermediate-advanced HCC patients.

PMID- 29654509
TI  - Realistic Vascular Replicator for TAVR Procedures.
AB  - Transcatheter aortic valve replacement (TAVR) is an over-the-wire procedure for
      treatment of severe aortic stenosis (AS). TAVR valves are conventionally tested
      using simplified left heart simulators (LHS). While those provide baseline
      performance reliably, their aortic root geometries are far from the anatomical in
      situ configuration, often overestimating the valves' performance. We report on a
      novel benchtop patient-specific arterial replicator designed for testing TAVR and
      training interventional cardiologists in the procedure. The Replicator is an
      accurate model of the human upper body vasculature for training physicians in
      percutaneous interventions. It comprises of fully-automated Windkessel mechanism
      to recreate physiological flow conditions. Calcified aortic valve models were
      fabricated and incorporated into the Replicator, then tested for performing TAVR
      procedure by an experienced cardiologist using the Inovare valve. EOA, pressures,
      and angiograms were monitored pre- and post-TAVR. A St. Jude mechanical valve was
      tested as a reference that is less affected by the AS anatomy. Results in the
      Replicator of both valves were compared to the performance in a commercial ISO
      compliant LHS. The AS anatomy in the Replicator resulted in a significant
      decrease of the TAVR valve performance relative to the simplified LHS, with EOA
      and transvalvular pressures comparable to clinical data. Minor change was seen in
      the mechanical valve performance. The Replicator showed to be an effective
      platform for TAVR testing. Unlike a simplified geometric anatomy LHS, it
      conservatively provides clinically-relevant outcomes and complement it. The
      Replicator can be most valuable for testing new valves under challenging patient
      anatomies, physicians training, and procedural planning.

PMID- 29654510
TI  - miR-128-3p regulates 3T3-L1 adipogenesis and lipolysis by targeting Pparg and
      Sertad2.
AB  - Differentiation of adipocytes and their aggregation to adipose tissue are
      critical for mammalian growth and development. MicroRNAs (miRNAs) are a class of
      endogenous small non-coding RNAs that play important roles in adipogenesis and
      lipid metabolism. miR-128-3p may contribute to adipose tissue development
      according to the previous studies. However, the role of miR-128-3p in the process
      of preadipocyte differentiation and lipid metabolism is not yet understood. The
      purpose of this research was to investigate the biological function and molecular
      mechanism of miR-128-3p in 3T3-L1 cells. In the present study, we found that miR
      128-3p was downregulated during the process of 3T3-L1 preadipocyte
      differentiation. Overexpression of miR-128-3p obstructed the expressions of
      adipogenic marker genes as well as the lipid droplets accumulation and
      triglyceride content, suggesting the importance of miR-128-3p for adipogenesis.
      Moreover, miR-128-3p could lead to the retardation of cell proliferation in 3T3
      L1 preadipocytes. Further evidences showed that, as a negative regulator of
      adipogenesis, miR-128-3p could directly target peroxisome proliferator-activated
      receptor gamma (Pparg) which resulted in the suppression of 3T3-L1 preadipocyte
      differentiation, and miR-128-3p could also bind with SERTA domain containing 2
      (Sertad2) which drove triglyceride hydrolysis and lipolysis. In addition,
      inhibition of Sertad2 with siRNA displayed the same effects as overexpression of
      miR-128-3p. Our research demonstrated that miR-128-3p impeded 3T3-L1 adipogenesis
      by targeting Pparg and Sertad2, resulting in the obstruction of preadipocyte
      differentiation and promotion of lipolysis. Taken together, this study offers
      profound insight into the mechanism of miRNA-mediated adipogenesis and lipid
      metabolism.

PMID- 29654512
TI  - [Injury prevention in amateur football with FIFA 11+ : What is implemented on the
      football pitch?]
AB  - BACKGROUND: The warm-up and injury prevention program FIFA 11+ was developed to
      reduce injuries in recreational and amateur level football. Despite systematic
      education it is uncertain what amount of knowledge is passed down to the lower
      recreational level football players and what exercises are implemented in the
      daily routine. This study presents the summarized experiences of German coaches
      about the implementation of exercises on the football pitch. MATERIAL AND
      METHODS: In this study 142 coaches who participated in 1 (of 5) of the 2-day
      courses between 2013 and 2017 were sent a questionnaire. The questionnaire
      consisted of 24 questions, which were developed by the football union of Lower
      Saxony. Incomplete questionnaires were excluded from the study. RESULTS: A total
      of 121 questionnaires could be analyzed, which is a response rate of 85.2%. The
      mean time period between the 2-day training and answering the questionnaire was
      29 months. Of the participating coaches 82.6% indicated that they use the program
      regularly (22% of the coaches use it twice a week or more frequently, 34% use it
      only once a week) and 6% of the coaches use additional programs to prevent
      injuries. A total of 86% of the participants believed in a reduction in the
      incidence of injuries induced by the FIFA 11+ concept, 89% of the participants
      rated the FIFA 11+ program as good ors very good, 91% rated the teaching concept
      as good or very good and 94% of the participants would recommend the 2-day
      advanced course to others. DISCUSSION: The prevention program as well as the
      advanced training concept were evaluated very positively. Most coaches use the
      program regularly. Nevertheless, many coaches use the FIFA 11+ exercises less
      than the recommended twice a week. Most coaches praised the good structure of the
      program, but also wished for the possibility of variations. CONCLUSION: The
      prevention program FIFA 11+ is seen by coaches in recreational and amateur
      football as an effective tool to prevent injury. Implementation on the football
      pitch is regular but not as frequent as the evidence-based recommendations in the
      training concept.

PMID- 29654513
TI  - [The new hemotherapy guideline].
AB  - The 2017 update of the German guidelines on hemotherapy is highly associated with
      the drug legislation and guidelines and thus necessitated a new structure of the
      contents. These guidelines reflect the state of the art for collection and
      application of blood and blood components corresponding to the Transfusion Act
      and is therefore the main document in hemotherapy. Topics of high interest in
      this 2017 update related to application of blood products are clarification and
      consent of patients, obligation for documentation, information, reporting and
      notification reports in the case of transfusion reactions and detailed
      description of quality management and quality assurance, as well as task
      description of persons responsible for the organization or implementation of
      transfusion-associated workflows. Surveillance, collating and management of
      errors are important prerequisites for the continuous optimization of patient
      safety. Patient blood management (PBM) as a requirement for the efficient use of
      blood products and the controlled and economical usage of autologous hemotherapy
      procedures (e. g. mechanical autotransfusion, MAT) are measures to reduce the
      need for blood products. All medical specialist societies, which carry out
      hemotherapy and participate in the standing committee of the Federal Medical
      Council (BAK) to revise the hemotherapy guidelines have to take care that the
      guidelines are understandable for medical doctors and the transfusion team.
      Additionally, the core principles of hemotherapy have to be described in a clear
      and distinct manner.

PMID- 29654511
TI  - Evidence for the link between defective autophagy and inflammation in peripheral
      blood mononuclear cells of type 2 diabetic patients.
AB  - Autophagy was shown to modulate inflammation in immune cells. This study was
      designed to evaluate the association between autophagy and inflammation in
      peripheral blood mononuclear cells (PBMCs) of type 2 diabetic (T2D) and non
      diabetic (ND) subjects. The autophagy markers were measured by real-time PCR and
      western blot. The gene expression of pro- and anti-inflammatory cytokines was
      assessed by real-time PCR. Reduced transcription of BECN1 and LAMP2 and unchanged
      expression of MAP1LC3B and ATG5 were observed in PBMCs of T2D patients. Decreased
      LC3B-II and increased p62/SQSTM1 levels were found in PBMCs of diabetic patients.
      The p-mTOR level was higher in PBMCs of diabetic patients. An increase in both IL
      1beta and TNF-alpha gene expression, along with a decrease in the expression of
      IL-10, was observed in PBMCs of T2D patients. TNF-alpha mRNA expression was
      inversely correlated with the mRNA expression of BECN1 and LAMP2. TNF-alpha and
      IL-1beta expression were negatively correlated with the protein levels of LC3B
      II. TNF-alpha and IL-1beta expression had also a positive correlation with
      protein level of p62. IL-10 mRNA expression was positively correlated with the
      mRNA expression of BECN1 and LAMP2 and protein levels of LC3B-II and negatively
      correlated with protein level of p62. In addition, p-mTOR level was positively
      correlated with IL-1beta and TNF-alpha mRNA expression. The results revealed a
      reduced autophagy in PBMCs of T2D patients that is liked with an enhanced
      inflammation. The suppression of autophagy in PBMCs of diabetic patients may be
      associated with the activation of the mTOR signaling.

PMID- 29654515
TI  - Five-year clinical follow-up of the STENTYS self-apposing stent in complex
      coronary anatomy: a single-centre experience with report of specific angiographic
      indications.
AB  - OBJECTIVES: We sought to investigate angiographic indications for the use of the
      STENTYS technique and evaluated the long-term safety and clinical efficacy of the
      stent. BACKGROUND: Coronary lesions involving complex anatomy, including
      aneurysmatic, ectatic, or tapered vessel segments often carry a substantial risk
      of stent malapposition. The self-apposing stent technique may reduce the risk of
      stent malapposition and therefore improve clinical outcomes. METHODS: A total of
      120 consecutive patients treated with the STENTYS stent were included (drug
      eluting stent (DES) n = 101, bare-metal stent (BMS) n = 19). All lesions were
      scored for angiographic indications for the STENTYS stent, including aneurysms,
      ectasias, tapering, absolute diameters, bifurcation lesions, and saphenous vein
      grafts. Off-line quantitative coronary angiography analyses were performed pre
      procedure and post-procedure. Five years follow-up was obtained including cardiac
      death, target vessel myocardial infarction (TV-MI), target vessel
      revascularisation, stent thrombosis, and the composite endpoint target vessel
      failure (cardiac death, TV-MI and target vessel revascularisation). RESULTS:
      Angiographic indications for STENTYS use were aneurysm (30%), ectasia (19%),
      tapering (27%), bifurcation lesions (8%), and saphenous vein graft lesions (16%)
      and absolute diameters (22%). Mean maximal diameter was 4.51 +/- 0.99 mm. At 5
      year follow-up target vessel failure rates were 24.1% in the total cohort (DES
      22.8% vs. BMS 33%, p = 0.26). Definite stent thrombosis rate was 3.8% at 5-year
      follow-up in this cohort with complex and high-risk lesions (DES 4.5% vs. BMS 0%,
      p = 0.39). CONCLUSIONS: Angiographic indications for the use of the self-apposing
      stent were complex lesions with atypical coronary anatomy. Our data showed
      reasonable stent thrombosis rates at 5-year follow-up, considering the high-risk
      lesion characteristics.

PMID- 29654516
TI  - Impact of different post-harvest processing methods on the chemical compositions
      of peony root.
AB  - The impact of key processing steps such as boiling, peeling, drying and storing
      on chemical compositions and morphologic features of the produced peony root was
      investigated in detail by applying 15 processing methods to fresh roots of
      Paeonia lactiflora and then monitoring contents of eight main components, as well
      as internal root color. The results showed that low temperature (4  degrees C)
      storage of fresh roots for approximately 1 month after harvest resulted in
      slightly increased and stable content of paeoniflorin, which might be due to
      suppression of enzymatic degradation. This storage also prevented roots from
      discoloring, facilitating production of favorable bright color roots. Boiling
      process triggered decomposition of polygalloylglucoses, thereby leading to a
      significant increase in contents of pentagalloylglucose and gallic acid. Peeling
      process resulted in a decrease of albiflorin and catechin contents. As a result,
      an optimized and practicable processing method ensuring high contents of the main
      active components in the produced root was developed.

PMID- 29654517
TI  - Ferroelectric Field Effect Induced Asymmetric Resistive Switching Effect in
      BaTiO3/Nb:SrTiO3 Epitaxial Heterojunctions.
AB  - Asymmetric resistive switching processes were observed in BaTiO3/Nb:SrTiO3
      epitaxial heterojunctions. The SET switching time from the high-resistance state
      to low-resistance state is in the range of 10 ns under + 8 V bias, while the
      RESET switching time from the low-resistance state to high-resistance state is in
      the range of 105 ns under - 8 V bias. The ferroelectric polarization screening
      controlled by electrons and oxygen vacancies at the BaTiO3/Nb:SrTiO3
      heterointerface is proposed to understand this switching time difference. This
      switch with fast SET and slow RESET transition may have potential applications in
      some special regions.

PMID- 29654514
TI  - A Review of Basal-Bolus Therapy Using Insulin Glargine and Insulin Lispro in the
      Management of Diabetes Mellitus.
AB  - : Basal-bolus therapy (BBT) refers to the combination of a long-acting basal
      insulin with a rapid-acting insulin at mealtimes. Basal insulin glargine 100 U/mL
      and prandial insulin lispro have been available for many years and there is a
      substantial evidence base to support the efficacy and safety of these agents when
      they are used in BBT or basal-plus therapy for patients with type 1 or type 2
      diabetes mellitus (T1DM, T2DM). With the growing availability of alternative
      insulins for use in such regimens, it seems timely to review the data regarding
      BBT with insulin glargine 100 U/mL and insulin lispro. In patients with T1DM, BBT
      with insulin glargine plus insulin lispro provides similar or better glycemic
      control and leads to less nocturnal hypoglycemia compared to BBT using human
      insulin as the basal and/or prandial component, and generally provides similar
      glycemic control and rates of severe hypoglycemia to those achieved with insulin
      lispro administered by continuous subcutaneous insulin infusion (CSII). Studies
      evaluating BBT with insulin glargine plus insulin lispro in patients with T2DM
      also demonstrate the efficacy and safety of these insulins. Available data
      suggest that BBT with insulin glargine and insulin lispro provides similar levels
      of efficacy and safety in pediatric and adult populations with T1DM and in adult
      patients and those aged more than 65 years with T2DM. These insulin preparations
      also appear to be safe and effective for controlling T2DM in people of different
      ethnicities and in patients with T1DM or T2DM and comorbidities. FUNDING: Eli
      Lilly and Company.

PMID- 29654519
TI  - [Comorbidities in heart failure : An interdisciplinary challenge].

PMID- 29654518
TI  - A model for rigorously applying the Exploration, Preparation, Implementation,
      Sustainment (EPIS) framework in the design and measurement of a large scale
      collaborative multi-site study.
AB  - BACKGROUND: This paper describes the means by which a United States National
      Institute on Drug Abuse (NIDA)-funded cooperative, Juvenile Justice-Translational
      Research on Interventions for Adolescents in the Legal System (JJ-TRIALS),
      utilized an established implementation science framework in conducting a multi
      site, multi-research center implementation intervention initiative. The
      initiative aimed to bolster the ability of juvenile justice agencies to address
      unmet client needs related to substance use while enhancing inter-organizational
      relationships between juvenile justice and local behavioral health partners.
      METHODS: The EPIS (Exploration, Preparation, Implementation, Sustainment)
      framework was selected and utilized as the guiding model from inception through
      project completion; including the mapping of implementation strategies to EPIS
      stages, articulation of research questions, and selection, content, and timing of
      measurement protocols. Among other key developments, the project led to a
      reconceptualization of its governing implementation science framework into
      cyclical form as the EPIS Wheel. The EPIS Wheel is more consistent with rapid
      cycle testing principles and permits researchers to track both progressive and
      recursive movement through EPIS. Moreover, because this randomized controlled
      trial was predicated on a bundled strategy method, JJ-TRIALS was designed to
      rigorously test progress through the EPIS stages as promoted by facilitation of
      data-driven decision making principles. The project extended EPIS by (1)
      elucidating the role and nature of recursive activity in promoting change
      (yielding the circular EPIS Wheel), (2) by expanding the applicability of the
      EPIS framework beyond a single evidence-based practice (EBP) to address varying
      process improvement efforts (representing varying EBPs), and (3) by disentangling
      outcome measures of progression through EPIS stages from the a priori established
      study timeline. DISCUSSION: The utilization of EPIS in JJ-TRIALS provides a model
      for practical and applied use of implementation frameworks in real-world settings
      that span outer service system and inner organizational contexts in improving
      care for vulnerable populations. TRIAL REGISTRATION: NCT02672150 .
      Retrospectively registered on 22 January 2016.

PMID- 29654520
TI  - Arabidopsis petiole torsions induced by lateral light or externally supplied
      auxin require microtubule-associated TORTIFOLIA1/SPIRAL2.
AB  - Although rather inconspicuous, movements are an important adaptive trait of
      plants. Consequently, light- or gravity-induced movements leading to organ
      bending have been studied intensively. In the field, however, plant movements
      often result in organ twisting rather than bending. This study investigates the
      mechanism of light- or gravity-induced twisting movements, coined "helical
      tropisms." Because certain Arabidopsis cell expansion mutants show organ twisting
      under standard growth conditions, we here investigated how the right-handed
      helical growth mutant tortifolia1/spiral2 (tor1) responds when stimulated to
      perform helical tropisms. When leaves were illuminated from the left, tor1 was
      capable of producing left-handed petiole torsions, but these occurred at a
      reduced rate. When light was applied from right, tor1 plants rotated their
      petioles much faster than the wild-type. Applying auxin to the lateral-distal
      side of wild-type petioles produced petiole torsions in which the auxinated flank
      was consistently turned upwards. This kind of movement was not observed in tor1
      mutants when auxinated to produce left-handed movements. Investigating auxin
      transport in twisting petioles based on the DR5-marker suggested that auxin flow
      was apical-basal rather than helical. While cortical microtubules of excised wild
      type petioles oriented transversely when stimulated with auxin, those of tor1
      were largely incapable of reorientation. Together, our results show that tor1 is
      a tropism mutant and suggest a mechanism in which auxin and microtubules both
      contribute to helical tropisms.

PMID- 29654521
TI  - Fully convolutional networks (FCNs)-based segmentation method for colorectal
      tumors on T2-weighted magnetic resonance images.
AB  - Segmentation of colorectal tumors is the basis of preoperative prediction,
      staging, and therapeutic response evaluation. Due to the blurred boundary between
      lesions and normal colorectal tissue, it is hard to realize accurate
      segmentation. Routinely manual or semi-manual segmentation methods are extremely
      tedious, time-consuming, and highly operator-dependent. In the framework of FCNs,
      a segmentation method for colorectal tumor was presented. Normalization was
      applied to reduce the differences among images. Borrowing from transfer learning,
      VGG-16 was employed to extract features from normalized images. We conducted five
      side-output blocks from the last convolutional layer of each block of VGG-16
      along the network, these side-output blocks can deep dive multiscale features,
      and produced corresponding predictions. Finally, all of the predictions from side
      output blocks were fused to determine the final boundaries of the tumors. A
      quantitative comparison of 2772 colorectal tumor manual segmentation results from
      T2-weighted magnetic resonance images shows that the average Dice similarity
      coefficient, positive predictive value, specificity, sensitivity, Hammoude
      distance, and Hausdorff distance were 83.56, 82.67, 96.75, 87.85%, 0.2694, and
      8.20, respectively. The proposed method is superior to U-net in colorectal tumor
      segmentation (P < 0.05). There is no difference between cross-entropy loss and
      Dice-based loss in colorectal tumor segmentation (P > 0.05). The results indicate
      that the introduction of FCNs contributed to accurate segmentation of colorectal
      tumors. This method has the potential to replace the present time-consuming and
      nonreproducible manual segmentation method.

PMID- 29654522
TI  - A prospective case study of high boost, high frequency emphasis and two-way
      diffusion filters on MR images of glioblastoma multiforme.
AB  - Glioblastoma multiforme (GBM) appears undifferentiated and non-enhancing on
      magnetic resonance (MR) imagery. As MRI does not offer adequate image quality to
      allow visual discrimination of the boundary between GBM focus and perifocal
      vasogenic edema, surgical and radiotherapy planning become difficult. The
      presence of noise in MR images influences the computation of radiation dosage and
      precludes the edge based segmentation schemes in automated software for radiation
      treatment planning. The performance of techniques meant for simultaneous
      denoising and sharpening, like high boost filters, high frequency emphasize
      filters and two-way anisotropic diffusion is sensitive to the selection of their
      operational parameters. Improper selection may cause overshoot and saturation
      artefacts or noisy grey level transitions can be left unsuppressed. This paper is
      a prospective case study of the performance of high boost filters, high frequency
      emphasize filters and two-way anisotropic diffusion on MR images of GBM, for
      their ability to suppress noise from homogeneous regions and to selectively
      sharpen the true morphological edges. An objective method for determining the
      optimum value of the operational parameters of these techniques is also
      demonstrated. Saturation Evaluation Index (SEI), Perceptual Sharpness Index
      (PSI), Edge Model based Blur Metric (EMBM), Sharpness of Ridges (SOR), Structural
      Similarity Index Metric (SSIM), Peak Signal to Noise Ratio (PSNR) and Noise
      Suppression Ratio (NSR) are the objective functions used. They account for
      overshoot and saturation artefacts, sharpness of the image, width of salient
      edges (haloes), susceptibility of edge quality to noise, feature preservation and
      degree of noise suppression. Two-way diffusion is found to be superior to others
      in all these respects. The SEI, PSI, EMBM, SOR, SSIM, PSNR and NSR exhibited by
      two-way diffusion are 0.0016 +/- 0.0012, 0.2049 +/- 0.0187, 0.0905 +/- 0.0408,
      2.64 * 1012 +/- 1.6 * 1012, 0.9955 +/- 0.0024, 38.214 +/- 5.2145 and 0.3547 +/-
      0.0069, respectively.

PMID- 29654523
TI  - The Promise of Telemedicine for Movement Disorders: an Interdisciplinary
      Approach.
AB  - PURPOSE OF REVIEW: Advances in technology have expanded telemedicine
      opportunities covering medical practice, research, and education. This is of
      particular importance in movement disorders (MDs), where the combination of
      disease progression, mobility limitations, and the sparse distribution of MD
      specialists increase the difficulty to access. In this review, we discuss the
      prospects, challenges, and strategies for telemedicine in MDs. RECENT FINDINGS:
      Telemedicine for MDs has been mainly evaluated in Parkinson's disease (PD) and
      compared to in-office care is cost-effective with similar clinical care, despite
      the barriers to engagement. However, particular groups including pediatric
      patients, rare MDs, and the use of telemedicine in underserved areas need further
      research. Interdisciplinary telemedicine and tele-education for MDs are feasible,
      provide similar care, and reduce travel costs and travel time compared to in
      person visits. These benefits have been mainly demonstrated for PD but serve as a
      model for further validation in other movement disorders.

PMID- 29654524
TI  - Highly Selective Detection of Cr3 + Ion with Colorimetric & Fluorescent Response
      Via Chemodosimetric Approach in Aqueous Medium.
AB  - So far, very few numbers of chemosensors for Cr3+ ion have been reported.
      However, the main drawback of reported receptors are the lack of selectivity and
      other trivalent cations such as Fe3+, Al3+ and anions like F- and -OAc frequently
      interfere with such assays. This paper present the synthesis, characterization &
      sensor studies of Schiff base containing naphthalene moiety which selectively
      detect Cr3+ ion by chemodosimetric approach. Using FT-IR, 1H NMR, 13C NMR and ESI
      mass spectroscopic techniques the probe was characterized. This receptor exhibit
      more selectivity and sensitivity towards Cr3+ than other divalent and trivalent
      cations like Mn2+, Zn2+, Co2+, Ni2+, Cd2+, Cu2+, Hg2+, Fe3+, and Al3+ ions. After
      the addition of chromium ion the receptor get change from yellow to colorless in
      aqueous medium. But no color change was observed on the addition of other metal
      ions. Using UV-Vis and PL studies, it was confirmed that the selective hydrolysis
      of imine group of receptor by Cr3+ ions takes place with high fluorescence
      enhancement that is corresponding to 1-naphthylamine. Receptor acts as selective
      chemodosimeter for Cr3+ ions with 2:1 stoichiometry and micro molar detection
      limit. This chemodosimetric approach was applied successfully for bio-imaging of
      HeLa cells.

PMID- 29654525
TI  - Detection of a case of Angelman syndrome caused by an imprinting error in 949
      pregnancies analyzed for AS following IVF.

PMID- 29654526
TI  - Safety and feasibility of laparoscopic surgery for appendiceal mucocele: a
      multicenter study.
AB  - BACKGROUND: Although laparoscopic appendectomy has been widely performed since
      1987, concerns over potential spillage of mucus into the peritoneal cavity during
      laparoscopic manipulation have prevented the use of laparoscopic surgery (LS) for
      appendiceal mucocele. The purpose of the present study was to evaluate the
      safety, feasibility, and short-term perioperative outcomes of LS for appendiceal
      mucocele. METHODS: A retrospective review was performed to identify patients
      diagnosed with appendiceal mucocele based on their imaging studies and who
      underwent surgery at one of six Hallym-University-affiliated hospitals between
      January 2007 and June 2016. Patient demographics, surgical outcomes, and
      postoperative outcomes were retrospectively analyzed. RESULTS: A total of 96
      patients were evaluated, of whom 58 underwent LS (LS group) and 38 underwent open
      surgery (OS; OS group). There were no significant differences in patient
      characteristics between groups. The operation time was similar in both groups (P
      = 0.399). Intraoperative rupture occurred in two patients in each group (no
      significant difference, P = 0.647). Time to flatus, time to soft food intake, and
      length of hospital stay were shorter in the LS group than in the OS group (2.4
      vs. 3.2 days, P = 0.003; 3.6 vs. 4.5 days, P = 0.024; 6.5 vs. 8.8 days, P =
      0.011, respectively). The rate of postoperative complications was similar between
      the groups (P = 0.786). Univariate analysis revealed that rupture of appendiceal
      mucocele was associated with white blood cell count > 10,000/uL (P = 0.032) but
      not with LS (P = 0.647). CONCLUSIONS: The results showed that LS is safe and
      feasible for the surgical treatment of appendiceal mucocele. An elevated WBC
      count was associated with a risk of appendiceal mucocele rupture.

PMID- 29654527
TI  - Laparoscopic management is feasible for nonobstetric surgical disease in all
      trimesters of pregnancy.
AB  - BACKGROUND: Nonobstetric surgical interventions are required in some women during
      pregnancy. The most common nonobstetric conditions requiring surgery during
      pregnancy are acute appendicitis and cholecystitis. This study aimed to evaluate
      pregnancy outcomes and complications following surgical procedures for presumed
      nonobstetric surgical interventions during pregnancy, and to compare the outcomes
      between the laparoscopic and open approaches. METHODS: We conducted a
      retrospective study of patients who underwent laparoscopic or open surgery during
      pregnancy for nonobstetric surgical indications at our institution between 2008
      and 2016. RESULTS: A total of 62 consecutive patients who underwent surgical
      intervention due to nonobstetric causes during pregnancy were included in our
      study. Of these, 35 (56.5%) were managed with laparoscopy and 27 (43.5%) with the
      open approach. Patients who underwent laparoscopy had a significantly shorter
      hospital stay and lower pain score on postoperative day 2 than those who
      underwent open surgery (5.5 vs. 7.2 days, p = 0.03 and 1.4 vs. 2.4, p < 0.01,
      respectively). There were no significant differences in operative complications
      between both groups. In advanced pregnancy (gestational age >= 23 weeks), 7
      patients (41.2%) were managed with laparoscopy and 10 (58.8%) with the open
      approach. No differences in surgical complications were found between both groups
      in advanced pregnancy as well. CONCLUSIONS: In our study, laparoscopic surgery
      was found to be feasible and safe in the late second and third trimesters as well
      as in the first and early second trimesters without adverse effects on pregnancy.

PMID- 29654528
TI  - Development and validation of surgical training tool: cystectomy assessment and
      surgical evaluation (CASE) for robot-assisted radical cystectomy for men.
AB  - BACKGROUND: We aimed to develop a structured scoring tool: cystectomy assessment
      and surgical evaluation (CASE) that objectively measures and quantifies
      performance during robot-assisted radical cystectomy (RARC) for men. METHODS: A
      multinational 10-surgeon expert panel collaborated towards development and
      validation of CASE. The critical steps of RARC in men were deconstructed into
      nine key domains, each assessed by five anchors. Content validation was done
      utilizing the Delphi methodology. Each anchor was assessed in terms of context,
      score concordance, and clarity. The content validity index (CVI) was calculated
      for each aspect. A CVI >= 0.75 represented consensus, and this statement was
      removed from the next round. This process was repeated until consensus was
      achieved for all statements. CASE was used to assess de-identified videos of RARC
      to determine reliability and construct validity. Linearly weighted percent
      agreement was used to assess inter-rater reliability (IRR). A logit model for
      odds ratio (OR) was used to assess construct validation. RESULTS: The expert
      panel reached consensus on CASE after four rounds. The final eight domains of the
      CASE included: pelvic lymph node dissection, development of the peri-ureteral
      space, lateral pelvic space, anterior rectal space, control of the vascular
      pedicle, anterior vesical space, control of the dorsal venous complex, and apical
      dissection. IRR > 0.6 was achieved for all eight domains. Experts outperformed
      trainees across all domains. CONCLUSION: We developed and validated a reliable
      structured, procedure-specific tool for objective evaluation of surgical
      performance during RARC. CASE may help differentiate novice from expert
      performances.

PMID- 29654529
TI  - Long-term functional outcomes of Roux-en-Y versus Billroth I reconstructions
      after laparoscopic distal gastrectomy for gastric cancer: a propensity-score
      matching analysis.
AB  - BACKGROUND: Only a few reports discuss long-term functional outcomes and changes
      observed in patients over several years following a distal gastrectomy. We
      investigated long-term functional outcomes and changes after laparoscopic distal
      gastrectomy based on the analysis of postoperative conditions and endoscopic
      findings observed in patients. METHODS: The study group comprised 159 patients
      who underwent Roux-en-Y reconstruction following laparoscopic distal gastrectomy
      (R-Y group) between December 2008 and November 2012 and 78 patients who underwent
      Billroth I reconstruction (B-I group) between January 2002 and November 2012. To
      minimize bias between the two groups, propensity scores were calculated using a
      logistic regression model. The groups were compared with respect to postoperative
      conditions and endoscopic findings at 1, 3, and 5 years postoperatively. RESULTS:
      The B-I group demonstrated more frequent heartburn than the R-Y group at 3 and 5
      years postoperatively. No significant differences were found in terms of loss of
      body weight and food intake. Endoscopic findings showed significantly lesser
      residual food and remnant gastritis in the R-Y group at each annual postoperative
      follow-up. The incidence of bile reflux and reflux esophagitis in the B-I group
      gradually increased over the years and showed a significant difference at the
      culmination of the 5-year postoperative follow-up, compared to the R-Y group.
      CONCLUSIONS: Roux-en-Y reconstruction was superior to Billroth I reconstruction
      in terms of frequency of occurrence of residual food, bile reflux, remnant
      gastritis, and reflux esophagitis in the long term. Differences between the two
      methods became more evident as the follow-up period lengthened.

PMID- 29654530
TI  - General practitioners' (GP) attitudes and knowledge about attention deficit
      hyperactivity disorder (ADHD) in Ireland.
AB  - BACKGROUND: ADHD is the most frequent reason for attendance at Child and
      Adolescent Mental Health Services (CAMHS). General practitioners (GPs) play a key
      role in recognising symptoms, referring for assessment and supporting ongoing
      treatment. However, there is an ambiguous understanding of ADHD among GPs, and
      different attitudes regarding the validity of ADHD as a construct. The present
      study aims to explore and identify GPs attitudes and beliefs about ADHD in the
      Irish context, and to find out the association of those attitudes with other
      factors. METHODS: Representative sample of qualified GPs registered to the Irish
      Medical Directory. The survey included questions about GPs' practice, attitudes
      towards ADHD, knowledge of symptoms and workup for ADHD, previous training and
      personal experience of ADHD. RESULTS: A hundred and forty GPs participated
      (response rate 28%). Factor analysis indicated 58.8% expressed a positive
      attitude towards ADHD. Those who have positive attitudes were more likely to be
      between 36 and 55 years old, seeing fewer children with suspected ADHD per year
      and working as part of a primary care team. Years of practice, personal
      experience of ADHD, training and knowledge in ADHD and access to CAMHS or
      psychology were not significantly related to either positive or negative ADHD
      attitudes. CONCLUSIONS: Despite the high rates of ADHD among children, a slim
      majority of Irish GPs have positive attitudes towards ADHD. This could lead to
      undiagnosed or misdiagnosed cases. Strategies need to be considered to address
      this.

PMID- 29654531
TI  - A profile of physiotherapy supply in Ireland.
AB  - BACKGROUND: The lack of information on public and private physiotherapy supply in
      Ireland makes current and future resource allocation decisions difficult. AIM:
      This paper estimates the supply of physiotherapists in Ireland and profiles
      physiotherapists across acute and non-acute sectors, and across public and
      private practice. It examines geographic variation in physiotherapist supply,
      examining the implications of controlling for healthcare need. METHODS:
      Physiotherapist headcounts are estimated using Health Service Personnel Census
      (HSPC) and Irish Society of Chartered Physiotherapists (ISCP) Register data.
      Headcounts are converted to whole-time equivalents (WTEs) using the HSPC and a
      survey of ISCP members to account for full- and part-time working practices. Non
      acute supply per 10,000 population in each county is estimated to examine
      geographic inequalities and the raw population is adjusted in turn for a range of
      need indicators. RESULTS: An estimated 3172 physiotherapists were practising in
      Ireland in 2015; 6.8 physiotherapists per 10,000, providing an estimated 2620
      WTEs. Females accounted for 74% of supply. Supply was greater in the non-acute
      sector; 1774 WTEs versus 846 WTEs in the acute sector. Physiotherapists in the
      acute sector were located mainly in publicly financed institutions (89%) with an
      even public/private split observed in the non-acute sector. Non-acute
      physiotherapist supply is unequally distributed across Ireland (Gini coefficient
      = 0.12; 95% CI 0.08-0.15), and inequalities remain after controlling for
      variations in healthcare needs across counties. CONCLUSION: The supply of
      physiotherapists in Ireland is 30% lower than the EU-28 average. Substantial
      inequality in the distribution of physiotherapists across counties is observed.

PMID- 29654532
TI  - Visual mental imagery influences attentional guidance in a visual-search task.
AB  - Visual mental imagery resembles visual working memory (VWM). Because both visual
      mental imagery and VWM involve the representation and manipulation of visual
      information, it was hypothesized that they would exert similar effects on visual
      attention. Several previous studies have demonstrated that working-memory
      representations guide attention toward a memory-matching task-irrelevant stimulus
      during visual-search tasks. Therefore, mental imagery may also guide attention
      toward imagery-matching stimuli. In the present study, five experiments were
      conducted to investigate the effects of visual mental imagery on visual attention
      during a visual-search task. Participants were instructed to visualize a color or
      an object clearly associated with a specific color, after which they were asked
      to detect a colored target in the visual-search task. Reaction times for target
      detection were shorter when the color of the target matched the imagined color,
      and when the color of the target was similar to that strongly associated with the
      imagined object, than when the color of the target did not match that of the
      mental representation. This effect was not observed when participants were not
      instructed to imagine a color. These results suggest that similar to VWM, visual
      mental imagery guides attention toward imagery-matching stimuli.

PMID- 29654533
TI  - Early tumor shrinkage is independently associated with improved overall survival
      among patients with metastatic renal cell carcinoma: a validation study using the
      COMPARZ cohort.
AB  - PURPOSE: Early tumor shrinkage (eTS) has prognostic value in metastatic renal
      cell carcinoma (mRCC). We aimed to validate the role of eTS in first line
      treatment from the COMPARZ study (NCT00720941). METHODS: 1100 patients treated
      with sunitinib or pazopanib were analyzed for tumor response according to RECIST
      1.0. eTS was defined as tumor shrinkage by >= 10%. A landmark analysis was
      performed on day (d) 42 and 90 and Cox proportional hazards regression was
      computed for the prognostic effect of eTS. RESULTS: In patients with eTS median
      OS was 34.1 [CI 95% 28.4; not reached (NR)] and 33.6 (CI 95% 30.1; NR) months
      (mo) at d 42 and 90, respectively, compared to 19.6 (CI 95% 14.0; 28.9) and 15.1
      (CI 95% 12.4; 18.7) mo for patients without eTS. There was no interaction between
      type of treatment and eTS (d 42 p = 0.79; d 90 p = 0.37). eTS >= 10% remained an
      independent prognostic marker in multivariable analyses at both d 42 and 90.
      CONCLUSIONS: Similar results were found for eTS at the 42 and 90 days landmarks.
      eTS >= 10% has prognostic relevance in mRCC and reflects a putative tool to guide
      future clinical treatment.

PMID- 29654535
TI  - Detecting Protein-Glycolipid Interactions Using CaR-ESI-MS and Model Membranes:
      Comparison of Pre-loaded and Passively Loaded Picodiscs.
AB  - Catch-and-release electrospray ionization mass spectrometry (CaR-ESI-MS),
      implemented using model membranes (MMs), is a promising approach for the
      discovery of glycolipid ligands of glycan-binding proteins (GBPs). Picodiscs
      (PDs), which are lipid-transporting complexes composed of the human sphingolipid
      activator protein saposin A and phospholipids, have proven to be useful MMs for
      such studies. The present work compares the use of conventional (pre-loaded) PDs
      with passively loaded PDs (PLPDs) for CaR-ESI-MS screening of glycolipids against
      cholera toxin B subunit homopentamer (CTB5). The pre-loaded PDs were prepared
      from a mixture of purified glycolipid and phospholipid or a mixture of lipids
      extracted from tissue, while the PLPDs were prepared by incubating PDs containing
      only phospholipid with glycolipid-containing lipid mixtures in aqueous solution.
      Time-dependent changes in the composition of the PLPDs produced by incubation
      with glycomicelles of the ganglioside GM1 were monitored using collision-induced
      dissociation of the gaseous PD ions and from the extent of ganglioside binding to
      CTB5 measured by ESI-MS. GM1 incorporation into PDs was evident within a few
      hours of incubation. At incubation times >= 10 days, GM1 binding to CTB5 was
      indistinguishable from that observed with pre-loaded PDs produced directly from
      GM1 at the same concentration. Comparison of ganglioside binding to CTB5 measured
      for pre-loaded PDs and PLPDs prepared from glycolipids extracted from pig and
      mouse brain revealed that the PLPDs allow for the detection of a greater number
      of ganglioside ligands. Together, the results of this study suggest PLPDs may
      have advantages over conventionally prepared PDs for screening glycolipids
      against GBPs using CaR-ESI-MS. Graphical Abstract ?.

PMID- 29654534
TI  - Characterization of Isomeric Glycans by Reversed Phase Liquid Chromatography
      Electronic Excitation Dissociation Tandem Mass Spectrometry.
AB  - The occurrence of numerous structural isomers in glycans from biological sources
      presents a severe challenge for structural glycomics. The subtle differences
      among isomeric structures demand analytical methods that can provide structural
      details while working efficiently with on-line glycan separation methods.
      Although liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a powerful
      tool for mixture analysis, the commonly utilized collision-induced dissociation
      (CID) method often does not generate a sufficient number of fragments at the MS2
      level for comprehensive structural characterization. Here, we studied the
      electronic excitation dissociation (EED) behaviors of metal-adducted,
      permethylated glycans, and identified key spectral features that could facilitate
      both topology and linkage determinations. We developed an EED-based, nanoscale,
      reversed phase (RP)LC-MS/MS platform, and demonstrated its ability to achieve
      complete structural elucidation of up to five structural isomers in a single LC
      MS/MS analysis. Graphical Abstract.

PMID- 29654538
TI  - Dual Pathways from Reactive Aggression to Depressive Symptoms in Children:
      Further Examination of the Failure Model.
AB  - The failure model posits that peer rejection and poor academic performance are
      dual pathways in the association between early aggressive behavior and subsequent
      depressive symptoms. We examined this model using an accelerated longitudinal
      design while also incorporating proactive and reactive aggression and gender
      moderation. Children in 1st, 3rd, and 5th grades (n = 912; ages 6-12; 48% female)
      were rated three times annually by their primary teachers on measures of
      proactive and reactive aggression, peer rejection, academic performance, and
      depressive symptoms. Using Bayesian cross-classified estimation to account for
      nested and planned-missing data, path models were estimated to examine whether
      early reactive aggression predicted subsequent peer rejection and academic
      performance, and whether these, in turn, predicted subsequent depressive
      symptoms. From 1st to 3rd grade, reactive aggression predicted peer rejection
      (not academic performance), proactive aggression predicted academic performance
      (not peer rejection), and academic performance and peer rejection both predicted
      depressive symptoms. From 3rd to 5th grade, however, neither peer rejection nor
      academic performance predicted subsequent depressive symptoms. Results were not
      moderated by gender. Overall, these findings provide mixed and limited support
      for the failure model among school-age children. Early reactive aggression may be
      a key risk factor for social problems, whereas proactive aggression may be linked
      to improved academic functioning. The "dual pathways" of peer rejection and
      academic performance may operate during early but not later elementary school.
      Limitations and implications are discussed.

PMID- 29654537
TI  - Quantification of Protein-Ligand Interactions by Laser Electrospray Mass
      Spectrometry.
AB  - Laser electrospray mass spectrometry (LEMS) measurement of the dissociation
      constant (Kd) for hen egg white lysozyme (HEWL) and N,N',N"-triacetylchitotriose
      (NAG3) revealed an apparent Kd value of 313.2 +/- 25.9 MUM for the ligand
      titration method. Similar measurements for N,N',N",N"'-tetraacetylchitotetraose
      (NAG4) revealed an apparent Kd of 249.3 +/- 13.6 MUM. An electrospray ionization
      mass spectrometry (ESI-MS) experiment determined a Kd value of 9.8 +/- 0.6 MUM.
      In a second LEMS approach, a calibrated measurement was used to determine a Kd
      value of 6.8 +/- 1.5 MUM for NAG3. The capture efficiency of LEMS was measured to
      be 3.6 +/- 1.8% and is defined as the fraction of LEMS sample detected after
      merging with the ESI plume. When the dilution is factored into the ligand
      titration measurement, the adjusted Kd value was 11.3 MUM for NAG3 and 9.0 MUM
      for NAG4. The calibration method for measuring Kd developed in this study can be
      applied to solutions containing unknown analyte concentrations. Graphical
      Abstract.

PMID- 29654536
TI  - Influence of Background H2O on the Collision-Induced Dissociation Products
      Generated from [UO2NO3].
AB  - Developing a comprehensive understanding of the reactivity of uranium-containing
      species remains an important goal in areas ranging from the development of
      nuclear fuel processing methods to studies of the migration and fate of the
      element in the environment. Electrospray ionization (ESI) is an effective way to
      generate gas-phase complexes containing uranium for subsequent studies of
      intrinsic structure and reactivity. Recent experiments by our group have
      demonstrated that the relatively low levels of residual H2O in a 2-D, linear ion
      trap (LIT) make it possible to examine fragmentation pathways and reactions not
      observed in earlier studies conducted with 3-D ion traps (Van Stipdonk et al. J.
      Am. Soc. Mass Spectrom. 14, 1205-1214, 2003). In the present study, we revisited
      the dissociation of complexes composed of uranyl nitrate cation [UVIO2(NO3)]+
      coordinated by alcohol ligands (methanol and ethanol) using the 2-D LIT. With
      relatively low levels of background H2O, collision-induced dissociation (CID) of
      [UVIO2(NO3)]+ primarily creates [UO2(O2)]+ by the ejection of NO. However, CID
      (using He as collision gas) of [UVIO2(NO3)]+ creates [UO2(H2O)]+ and UO2+ when
      the 2-D LIT is used with higher levels of background H2O. Based on the results
      presented here, we propose that product ion spectrum in the previous experiments
      was the result of a two-step process: initial formation of [UVIO2(O2)]+ followed
      by rapid exchange of O2 for H2O by ion-molecule reaction. Our experiments
      illustrate the impact of residual H2O in ion trap instruments on the product ions
      generated by CID and provide a more accurate description of the intrinsic
      dissociation pathway for [UVIO2(NO3)]+. Graphical Abstract ?.

PMID- 29654539
TI  - Polyvictimization, Emotion Dysregulation, Symptoms of Posttraumatic Stress
      Disorder, and Behavioral Health Problems among Justice-Involved Youth: a Latent
      Class Analysis.
AB  - Among the 90% of adolescents involved in juvenile justice who have experienced
      traumatic victimization, a sub-group may be at highest risk due to histories of
      multiple types of interpersonal and non-interpersonal trauma, termed polyvictims.
      Latent class analyses (LCA) have identified polyvictimized subgroups in several
      studies of adolescents and adults, but only one study of traumatic victimization
      has been conducted with justice-involved youth (Ford et al. 2013). The current
      investigation replicates and extends that study's findings using LCA to assess a
      wider range of victimization- and nonvictimization-related adversities and
      emotion dysregulation, DSM-5 symptom clusters of posttraumatic stress disorder
      (PTSD), and behavioral health problems, such as substance use, anger, depression,
      somatic complaints, and suicide ideation. In a sample of juvenile detainees three
      latent classes were identified: mixed adversity (MA; n = 327), violent
      environment (VE; n = 337), and polyvictimization (PV; n = 145). In contrast to MA
      youth, PV youth were more likely to report exposure to all forms of adversity,
      and in contrast to both MA and VE youth, exposure to maltreatment and family
      violence, and higher levels of emotion dysregulation, PTSD, and
      depression/anxiety symptoms, somatic complaints, and suicidality. VE youth (vs.
      MA youth) were more likely to report exposure to violence and non-interpersonal
      traumas, and were higher on some forms of emotion dysregulation, PTSD symptoms,
      anger and substance use. Findings suggest that most justice-involved youth have
      experienced substantial adversity, with almost one in five identified as a
      polyvictim having experienced multiple adversities, including impaired
      caregivers, and evidencing the most severe problems in emotion dysregulation and
      PTSD, internalizing, and externalizing symptoms.

PMID- 29654540
TI  - A Randomized Trial Evaluating School-Based Mindfulness Intervention for Ethnic
      Minority Youth: Exploring Mediators and Moderators of Intervention Effects.
AB  - The study examined the efficacy of a school-based mindfulness intervention on
      mental health and emotion regulation outcomes among adolescents in a wait-list
      controlled trial. The study also explored mediators and moderators of
      intervention effects. A total of 145 predominantly ethnic minority (Asian and
      Latino) 9th grade students with elevated mood symptoms were randomized to receive
      a 12-week mindfulness intervention at the start of the academic year, or in the
      second semester of the year. Students completed measures of emotion regulation
      and mental health symptoms at baseline, post-intervention, and 3-month follow-up.
      Intent-to-treat analyses revealed significant treatment effects of the
      mindfulness intervention for internalizing symptoms and perceived stress at post
      treatment. Pooled pre-to-post treatment analyses of the entire sample revealed a
      small effect size for attention problems, medium for internalizing and
      externalizing problems, and large for perceived stress. We also found a small
      effect size for cognitive reappraisal, medium for expressive suppression,
      emotional processing, emotional expression, and rumination and large for
      avoidance fusion. Mediation analyses showed that treatment effects on
      internalizing symptoms and perceived stress were mediated by reductions in
      expressive suppression and rumination. Moderation analyses revealed that
      treatment effects were larger among youth with more severe problems at baseline
      for internalizing problems, externalizing problems, and perceived stress.
      However, for attention problems, students with lower severity at baseline
      appeared to have larger treatment gains. The study provided evidence that
      mindfulness intervention was beneficial for low-income ethnic minority youth in
      reducing perceived stress and internalizing problems, and improving emotion
      regulation outcomes. Furthermore, mindfulness training was associated with
      reduced mental health symptoms via improvements in emotion regulation.

PMID- 29654541
TI  - Electric ultrafreezer (- 150  degrees C) as an alternative for zebrafish sperm
      cryopreservation and storage.
AB  - Zebrafish sperm cryopreservation is a fundamental methodology to manage and back
      up valuable genetic resources like transgenic and mutant strains.
      Cryopreservation usually requires liquid nitrogen for storage, which is expensive
      and hazardous. Our objective was to evaluate if electric ultrafreezers (- 150 
      degrees C) are a viable alternative for zebrafish sperm storage. Zebrafish sperm
      was cryopreserved in the same conditions (- 20  degrees C/min), stored either in
      liquid nitrogen or in an ultrafreezer, and thawed after 1 week, 1 month, and 3
      months. Sperm motility, membrane integrity, and fertilization ability were
      assessed. There were no significant differences in motility and hatching rate
      throughout storage time. Additionally, we aimed at understanding if
      cryopreservation directly in an ultrafreezer (- 66  degrees C/min) could improve
      post-thaw sperm quality. Freezing at - 20  degrees C/min was performed as before,
      and compared to samples cryopreserved with a fast cooling rate by placing
      directly in an ultrafreezer (- 66  degrees C/min). Sperm quality was assessed
      according to motility, viability, DNA fragmentation, and apoptosis (annexin V).
      The - 66  degrees C/min cooling rate showed significantly higher membrane and DNA
      integrity, and lower number of cells in late apoptosis in comparison to the other
      treatments. This study showed that zebrafish sperm cryopreservation and storage
      in an ultrafreezer system is possible and a fast cooling rate directly in
      ultrafreezer improves post-thaw sperm quality.

PMID- 29654542
TI  - Pentosan Polysulfate Treatment of Mucopolysaccharidosis Type IIIA Mice.
AB  - : Overall Goal: This study was designed to evaluate the impact of pentosan
      polysulfate (PPS) treatment on mice with mucopolysaccharidosis (MPS) type IIIA
      (Sanfilippo A syndrome; OMIM 252900). PROTOCOL: Three groups of MPS IIIA mice
      were evaluated: 1-week-old mice treated with subcutaneous (subQ) PPS at 25 mg/kg
      once weekly for 31 weeks (group 1); 5-month-old mice treated with subQ PPS once
      weekly at 50 mg/kg for 12 weeks (group 2); and 5-week-old mice treated by
      continual intracerebroventricular (ICV) PPS infusion for 11 weeks (60
      MUg/kg/day). Treated MPS IIIA mice and controls were assessed by measuring plasma
      cytokine levels, histologic analyses of systemic organs, and analyses of various
      neuroinflammatory, neurodegenerative, and lysosomal disease markers in their
      brains. Neurobehavioral testing also was carried out. RESULTS: As seen in other
      MPS animal models, subQ PPS treatment reduced plasma cytokine levels and
      macrophage infiltration in systemic tissues. ICV administration did not elicit
      these systemic effects. SubQ PPS administration also significantly impacted brain
      neuropathology, inflammation, and behavior. The effect of early subQ treatment
      was more significant than dose. Surprisingly, ICV PPS treatment had intermediate
      effects on most of these brain markers, perhaps due to the limited dose and/or
      duration of treatment. Consistent with these neuropathological findings, we also
      observed significant improvements in the hyperactivity/anxiety and learning
      behaviors of the MPS IIIA mice treated with early subQ PPS.

PMID- 29654543
TI  - Muscle Weakness, Cardiomyopathy, and L-2-Hydroxyglutaric Aciduria Associated with
      a Novel Recessive SLC25A4 Mutation.
AB  - BACKGROUND: Mutations in SLC25A4 (syn. ANT1, Adenine nucleotide translocase, type
      1) are known to cause either autosomal dominant progressive external
      ophthalmoplegia (adPEO) or recessive mitochondrial myopathy, hypertrophic
      cardiomyopathy, and lactic acidosis. METHODS AND RESULTS: Whole exome sequencing
      in a young man with myopathy, subsarcolemmal mitochondrial aggregations,
      cardiomyopathy, lactic acidosis, and L-2-hydroxyglutaric aciduria (L-2-HGA)
      revealed a new homozygous mutation in SLC25A4 [c.653A>C, NM_001151], leading to
      the replacement of a highly conserved glutamine by proline [p.(Q218P); NP_001142]
      that most likely affects the folding of the ANT1 protein. No pathogenic mutation
      was found in L2HGDH, which is associated with "classic" L-2-HGA. Furthermore, L-2
      HGDH enzymatic activity in the patient fibroblasts was normal. Long-range PCR and
      Southern blot confirmed absence of mtDNA-deletions in blood and muscle.
      CONCLUSION: The disturbed ADP/ATP transport across the inner mitochondrial
      membrane may lead to an accumulation of different TCA-cycle intermediates such as
      2-ketoglutarate (2-KG) in our patient. As L-2-HG is generated from 2-KG we
      hypothesize that the L-2-HG increase is a secondary effect of 2-KG accumulation.
      Hence, our report expands the spectrum of laboratory findings in ANT1-related
      diseases and hints towards a connection with organic acidurias.

PMID- 29654544
TI  - Alkaptonuria Severity Score Index Revisited: Analysing the AKUSSI and Its
      Subcomponent Features.
AB  - BACKGROUND: Alkaptonuria (AKU) is a rare disorder with no licensed treatment;
      nitisinone may reduce symptoms and progression. The All Alkaptonuria Severity
      Score Index (AKUSSI) measures disease severity in clinical, joint and spine
      domains, with 57 subcomponent feature scores. Our primary aim was to assess tools
      for validating scores such as the AKUSSI by detecting relationships between
      features both before and during nitisinone treatment. METHODS: AKUSSI
      measurements from nitisinone-treated patients visiting the National AKU Centre
      between 01-Jun-2012 and 31-May-2016 were analysed pre-treatment, at first
      treatment and annually to Year 3 post-treatment. Principal component analysis
      (PCA) and redundancy analysis assessed whether any AKUSSI features contributed
      little information to the overall score. RESULTS: 65 AKU patients were included:
      17 with a pre-treatment AKUSSI measurement (10 later received nitisinone) and 48
      with a first measurement at their first treatment visit. In PCA, the first four
      principal components (PC1-PC4) explained >=50% of AKUSSI variance at all visits
      (54.1-87.3%). Some features regularly dominated their domain's PC1: ears, aortic
      sclerosis, and nasal/temporal eye scores (clinical), pain-related scores (joint)
      and cervical, lumbar and thoracic spine scores (spine). Only the right-hand/wrist
      score was consistently redundant. Right eye (nasal) and left ear scores were
      redundant pre-treatment, potentially correlating with other dominant clinical PC1
      features. CONCLUSIONS: PCA and redundancy analysis supported the AKUSSI as a
      robust AKU disease severity measure, although some AKUSSI features could be
      removed for simplicity. For small patient populations and rare diseases, PCA and
      redundancy analysis together can aid validation of disease severity metrics.

PMID- 29654545
TI  - Cognitive Impairments and Subjective Cognitive Complaints in Fabry Disease: A
      Nationwide Study and Review of the Literature.
AB  - Fabry disease is a rare progressive X-linked lysosomal storage disorder which
      leads to neuropathic pain, organ dysfunction and cerebral pathology. Few studies
      have investigated cognitive impairment in Fabry disease and these previous
      studies are difficult to compare due to heterogeneous methodological designs and
      small cohorts. The objective was to investigate the frequency of cognitive
      impairment in the Danish nationwide cohort of Fabry patients. Further, we
      examined if subjective cognitive complaints were associated with objective
      cognitive performances in this patient group. Neuropsychological tests (17
      measures) and evaluation of subjective complaints with the Perceived Deficits
      Questionnaire (PDQ) were applied in 41 of 63 patients. According to an a priori
      definition, 12 patients (29.3%) were cognitively impaired. Tests tapping
      psychomotor speed, attention and executive functions had the highest frequency of
      impairment. In general, disease related variables as Mainz Severity Score Index,
      enzyme activity and years since onset and depression did not have a significant
      impact on the categorisation of patients as being cognitively impaired or non
      impaired. Thus, cognitive impairment in Fabry disease does not seem to occur
      solely by having symptoms for many years or by having high disease burden.
      However, impaired neuropsychological test results were significantly more common
      in patients with cerebrovascular disease. Only three patients had scores in the
      abnormal range of the PDQ scale and subjective perceptions of cognition were not
      associated with cognitive performances. The levels of subjective cognitive
      complaints were generally very low in the studied patients demonstrating that the
      absence of subjective cognitive complaints does not exclude the presence of
      objective cognitive problems.

PMID- 29654546
TI  - Neonatal Onset Interstitial Lung Disease as a Primary Presenting Manifestation of
      Mucopolysaccharidosis Type I.
AB  - We describe two cases of neonatal onset interstitial lung disease eventually
      diagnosed as mucopolysaccharidosis type I (MPS I). In both cases, evaluation led
      to lung biopsy, pathology review, and identification of glycogen deposition.
      Pulmonary interstitial glycogenosis (PIG) was considered as a clinical diagnosis
      in case one; however, further review of electron microscopy (EM) was more
      consistent with MPS I rather than PIG. Both cases were confirmed to have MPS I by
      enzyme and molecular analysis. Neonatal interstitial lung disease is an atypical
      presentation for MPS I which is likely under-recognized. Diagnosis through
      clinical guidelines and a multidisciplinary approach had a major impact on
      patient management. The diagnosis of MPS I prompted timely initiation of enzyme
      replacement therapy (ERT) and the patients ultimately underwent hematopoietic
      stem cell transplantation (HSCT) to improve symptomatic outcomes. In addition to
      treatment, immediate precautionary recommendations were made to avoid potentially
      catastrophic outcomes associated with cervical instability. These cases add to
      the clinical spectrum of MPS I in the newborn period. They further illustrate the
      difficulties in early recognition of the disease, and importance of a definitive
      diagnosis of MPS I in infants with interstitial lung disease.

PMID- 29654547
TI  - Serum Amino Acid Profiling in Citrin-Deficient Children Exhibiting Normal Liver
      Function During the Apparently Healthy Period.
AB  - BACKGROUND: Citrin (mitochondrial aspartate-glutamate transporter) deficiency
      causes the failures in both carbohydrate-energy metabolism and the urea cycle,
      and the alterations in the serum levels of several amino acids in the stages of
      newborn (NICCD) and adult (CTLN2). However, the clinical manifestations are
      resolved between the NICCD and CTLN2, but the reasons are still unclear. This
      study evaluated the serum amino acid profile in citrin-deficient children during
      the healthy stage. METHODS: Using HPLC-MS/MS analysis, serum amino acids were
      evaluated among 20 citrin-deficient children aged 5-13 years exhibiting normal
      liver function and 35 age-matched healthy controls. RESULTS: The alterations in
      serum amino acids characterized in the NICCD and CTLN2 stages were not observed
      in the citrin-deficient children. Amino acids involved in the urea cycle,
      including arginine, ornithine, citrulline, and aspartate, were comparable in the
      citrin-deficient children to the respective control levels, but serum urea was
      twofold higher, suggestive of a functional urea cycle. The blood sugar level was
      normal, but glucogenic amino acids and glutamine were significantly decreased in
      the citrin-deficient children compared to those in the controls. In addition,
      significant increases of ketogenic amino acids, branched-chain amino acids
      (BCAAs), a valine intermediate 3-hydroxyisobutyrate, and beta-alanine were also
      found in the citrin-deficient children. CONCLUSION: The profile of serum amino
      acids in the citrin-deficient children during the healthy stage showed different
      characteristics from the NICCD and CTLN2 stages, suggesting that the failures in
      both urea cycle function and energy metabolism might be compensated by amino acid
      metabolism. SYNOPSIS: In the citrin-deficient children during the healthy stage,
      the characteristics of serum amino acids, including decrease of glucogenic amino
      acids, and increase of ketogenic amino acids, BCAAs, valine intermediate, and
      beta-alanine, were found by comparison to the age-matched healthy control
      children, and it suggested that the characteristic alteration of serum amino
      acids may be resulted from compensation for energy metabolism and ammonia
      detoxification.

PMID- 29654548
TI  - Reduced Muscle Strength in Barth Syndrome May Be Improved by Resistance Exercise
      Training: A Pilot Study.
AB  - BACKGROUND: Cardioskeletal myopathy is thought to contribute to exercise
      intolerance, and reduced quality of life (QOL) in Barth syndrome (BTHS). The
      objectives of this study were to examine: (1) skeletal muscle
      strength/performance in adolescents and young adults with BTHS and (2) the
      safety, feasibility, and initial efficacy of 12 weeks of progressive resistance
      exercise training (RET) on muscle strength, mass, and performance, bone mineral
      density, exercise tolerance, cardiac function, and QOL in individuals with BTHS.
      METHODS: Individuals with BTHS (n = 9, 23 +/- 6 years), and age-, sex-, and
      activity level-matched unaffected Controls (n = 7, 26 +/- 5 years) underwent
      baseline testing to assess muscle performance, exercise capacity, cardiac
      structure and function, body composition, and health-related QOL. Subsequently, n
      = 3 participants with BTHS performed 12 weeks of supervised RET (60 min per
      session, 3 sessions/week). All testing was repeated post-RET. RESULTS: BTHS had
      lower strength and lean muscle mass compared to Controls (all p < 0.05). BTHS
      also had diminished lower extremity, upper extremity, thoracic spine, lumbar
      spine, and pelvic bone mineral density (all p < 0.05) and reduced exercise
      capacity (p < 0.001) compared to Controls. RET was well-tolerated and attended,
      was not associated with any adverse events, and significantly increased muscle
      strength (p < 0.05). CONCLUSIONS: Individuals with BTHS demonstrate reduced
      muscle strength and mass, bone mineral density, and exercise capacity. RET
      appears safe and well-tolerated in BTHS and promotes increased muscle strength.
      Larger studies are needed to confirm these improvements and to fully determine
      the effects of RET in individuals with BTHS.

PMID- 29654550
TI  - Bicompartmental (uni plus patellofemoral) versus total knee arthroplasty: a match
      paired study.
AB  - BACKGROUND: Osteoarthritis (OA) of the knee, whether primary or post-traumatic,
      does not always involve all three compartments (tibiofemoral medial and lateral
      and the patellofemoral ones). Bicompartmental knee arthroplasty (BKA) was
      proposed as a good alternative to total knee arthroplasty when two of the three
      knee compartments were affected. MATERIALS AND METHODS: We performed a
      retrospective comparative study collecting all BKAs performed between March 2010
      and January 2016. During this period, we treated 27 patients with BKA for medial
      or lateral and patellofemoral OA. Seven of them were lost to follow-up and were
      not included in the study. Group A (BKA group) was compared to a homogeneous
      group of 20 patients who underwent TKA during the same period (group B). RESULTS:
      Patients treated with TKA were younger than those treated with BKA (mean age 65
      vs. 67.2; p = 0.2149). BKA resulted in longer mean operating time (87 vs. 82.4
      min; p = 0.2983), less blood loss (413 vs. 458 ml; p = 0.0052) but higher blood
      transfusion rate (12 vs. 10%). Medium follow-up was 34 months for BKA group and
      38 months for TKA group. No statistically significant differences were found in
      KSS score between the two groups (KSS score 92.3 for BKA, 94.5 for TKA; p =
      0.5221; KSS function was 87.2 for BKA and 89.2 for TKA; p = 0.4985). CONCLUSION:
      The most important finding of the present study was that although BKA seemed to
      be theoretically more favorable in terms of functional recovery and blood loss,
      patients of group A had lower KSS score and higher transfusion rate than those of
      group B. Our data confirm that BKA could be proposed as an alternative to TKA,
      especially in young and high-demanding patients.

PMID- 29654549
TI  - Severe Leukoencephalopathy with Clinical Recovery Caused by Recessive BOLA3
      Mutations.
AB  - AIM: To identify the genetic aetiology of a distinct leukoencephalopathy causing
      acute neurological regression in infancy with apparently complete clinical
      recovery. METHODS: We performed trio whole genome sequencing (WGS) to determine
      the genetic basis of the disorder. Mitochondrial function analysis in cultured
      patient fibroblasts was undertaken to confirm the pathogenicity of candidate
      variants. RESULTS: The patient presented at 18 months with acute hemiplegia and
      cognitive regression without obvious trigger. This was followed by clinical
      recovery over 4 years. MRI at disease onset revealed bilateral T2 hyperintensity
      involving the periventricular and deep white matter and MR spectroscopy of
      frontal white matter demonstrated a lactate doublet. Lactate levels and
      mitochondrial respiratory chain enzyme activity in muscle, liver and fibroblasts
      were normal. Plasma glycine was elevated. The MRI abnormalities improved. WGS
      identified compound heterozygous variants in BOLA3: one previously reported
      (c.136C>T, p.Arg46*) and one novel variant (c.176G>A, p.Cys59Tyr). Analysis of
      cultured patient fibroblasts demonstrated deficient pyruvate dehydrogenase (PDH)
      activity and reduced quantity of protein subunits of mitochondrial complexes I
      and II, consistent with BOLA3 dysfunction. Previously reported cases of multiple
      mitochondrial dysfunctions syndrome 2 (MMDS2) with hyperglycinaemia caused by
      BOLA3 mutations have leukodystrophy with severe, progressive neurological and
      multisystem disease. CONCLUSIONS: We report a novel phenotype for MMDS2
      associated with apparently complete clinical recovery and partial resolution of
      MRI abnormalities. We have identified a novel disease-causing variant in BOLA3
      validated by functional cellular studies. Our patient's clinical course broadens
      the phenotypic spectrum of MMDS2 and highlights the potential for some genetic
      leukoencephalopathies to spontaneously improve.

PMID- 29654551
TI  - Reconstruction of failed acetabular component in the presence of severe
      acetabular bone loss: a systematic review.
AB  - Acetabular revision especially in the presence of severe bone loss is
      challenging. There is a paucity of literature critiquing contemporary techniques
      of revision acetabular reconstruction and their outcomes. The purpose of this
      study was to systematically review the literature and to report clinical outcomes
      and survival of contemporary acetabular revision arthroplasty techniques
      (tantalum metal shells, uncemented revision jumbo shells, reinforced cages and
      rings, oblong shells and custom-made triflange constructs). Full-text papers and
      those with an abstract in English published from January 2001 to January 2016
      were identified through international databases. A total of 50 papers of level IV
      scientific evidence, comprising 2811 hips in total, fulfilled the inclusion
      criteria and were included. Overall, patients had improved outcomes irrespective
      of the technique of reconstruction as documented by postoperative hip scores. Our
      pooled analysis suggests that oblong cups components had a lower failure rate
      compared with other different materials considered in this review. Custom-made
      triflange cups had one of highest failure rates. However, this may reflect the
      complexity of revisions and severity of bone loss. The most common postoperative
      complication reported in all groups was dislocation. This review confirms
      successful acetabular reconstructions using diverse techniques depending on the
      type of bone loss and highlights key features and outcomes of different
      techniques. In particular, oblong cups and tantalum shells have successful
      survivorship.

PMID- 29654552
TI  - Investigations of cortical and cancellous clavicle bone patterns reveal an
      explanation for the load transmission and the higher incidence of lateral
      clavicle fractures in the elderly: a CT-based cadaveric study.
AB  - Clavicle fracture is known to be one of the injuries frequently occurring in the
      elderly. The purpose of this study was to characterise the internal structures
      that might correlate with the higher incidence of lateral clavicle fracture in
      the elderly. Twenty clavicles were collected from ten Japanese cadavers ranging
      from 70 to 99 years (83.6 +/- 7.6), scanned, and three-dimensional computed
      tomography (3D CT) images reconstructed. The clavicle lengths were divided into
      five equal segments. The four demarcation lines from the acromial end of the
      clavicle were defined as the observation points A, B, C, and D. The clavicles
      were then measured and analysed. It was shown that along the clavicles
      observation point A was the widest and points B and C the narrowest. Regarding
      the thickness, point D was the thickest among all four points, and there was no
      significant difference among the points A, B, and C. No male-female difference
      was found in either the cortical or cancellous bone ratio at all four points.
      Interestingly, the highest cortical bone ratio was observed at point B and the
      ratio was significantly decreased toward either end. The cancellous bone ratio
      was highest at point C and decreased toward both ends. Further observations
      showed that there were rays of trabeculae around point A, spreading from the
      superior-posterior edge or anterior edge toward each other and toward the lateral
      end and point B. Characteristics in the cortical and cancellous bone ratios and
      cancellous bone patterns might shed light on understanding the fractures in the
      lateral portion of the clavicle in the elderly.

PMID- 29654553
TI  - Study on real-time force feedback for a master-slave interventional surgical
      robotic system.
AB  - In robot-assisted catheterization, haptic feedback is important, but is currently
      lacking. In addition, conventional interventional surgical robotic systems
      typically employ a master-slave architecture with an open-loop force feedback,
      which results in inaccurate control. We develop herein a novel real-time master
      slave (RTMS) interventional surgical robotic system with a closed-loop force
      feedback that allows a surgeon to sense the true force during remote operation,
      provide adequate haptic feedback, and improve control accuracy in robot-assisted
      catheterization. As part of this system, we also design a unique master control
      handle that measures the true force felt by a surgeon, providing the basis for
      the closed-loop control of the entire system. We use theoretical and empirical
      methods to demonstrate that the proposed RTMS system provides a surgeon (using
      the master control handle) with a more accurate and realistic force sensation,
      which subsequently improves the precision of the master-slave manipulation. The
      experimental results show a substantial increase in the control accuracy of the
      force feedback and an increase in operational efficiency during surgery.

PMID- 29654554
TI  - Evaluation of Epstein-Barr Virus Salivary Shedding in HIV/AIDS Patients and HAART
      Use: A Retrospective Cohort Study.
AB  - Little data is available on the evaluation of the occurrence rates of Epstein
      Barr virus (EBV) in saliva and relationship with highly active antiretroviral
      therapy (HAART) use in HIV/AIDS patients in China. We conducted a retrospective
      cohort study of EBV serological tests for HIV/AIDS patients who were treated in
      the hospitals for infectious diseases in Wuxi and Shanghai, China from May 2016
      to April 2017. The EBV-seropositive samples were identified by ELISA. EBV
      specific primers and probes were used for the quantitative detection of viral DNA
      from saliva via quantitative real-time polymerase chain reaction. CD4 cell counts
      of the HIV/AIDS patients were detected by a flow cytometry. A total of 372
      HIV/AIDS patients were ultimately selected and categorized for this retrospective
      cohort study. For EBV IgG and IgM, the HIV/AIDS HAART use (H) and non-HAART use
      (NH) groups had significantly higher seropositive rates than the HIV-negative
      control group. The HIV/AIDS (NH) group had the highest seropositive rate (IgG,
      94.27%; IgM, 68.98%) and the highest incidence of EBV reactivation or infection.
      For salivary EBV DNA-positive rates and quantities, the HIV/AIDS (H) (73.69%) and
      the HIV/AIDS (NH) (100%) groups showed significantly higher values than the HIV
      negative control group (35.79%, > twofold). Further, the salivary EBV DNA
      negative population had significantly higher CD4 cell counts than the EBV DNA
      positive population in the HIV/AIDS (H) group and the HIV/AIDS (NH) groups. Thus,
      HAART use is beneficial in decreasing the EBV salivary shedding in HIV/AIDS
      patients and indirectly decreases EBV transmission risk.

PMID- 29654556
TI  - The effect of resistant starch (RS) on the bovine rumen microflora and isolation
      of RS-degrading bacteria.
AB  - Resistant starch (RS) in the diet reaches the large intestine without
      degradation, where it is decomposed by the commensal microbiota. The fermentation
      of RS produces secondary metabolites including short-chain fatty acids (SCFAs),
      which have been linked to a variety of physiological and health effects.
      Therefore, the availability of RS as a prebiotic is a current issue. The
      objectives of this study were (1) to use metagenomics to observe microbial flora
      changes in Bos taurus coreanae rumen fluid in the presence of RS and (2) to
      isolate RS-degrading microorganisms. The major microbial genus in a general rumen
      fluid was Succiniclasticum sp., whereas Streptococcus sp. immediately
      predominated after the addition of RS into the culture medium and was then
      drastically replaced by Lactobacillus sp. The presence of Bifidobacterium sp. was
      also observed continuously. Several microorganisms with high RS granule-degrading
      activity were identified and isolated, including B. choerinum FMB-1 and B.
      pseudolongum FMB-2. B. choerinum FMB-1 showed the highest RS-hydrolyzing activity
      and degraded almost 60% of all substrates tested. Coculture experiments
      demonstrated that Lactobacillus brevis ATCC 14869, which was isolated from human
      feces, could grow using reducing sugars generated from RS by B. choerinum FMB-1.
      These results suggest that Bifidobacterium spp., especially B. choerinum FMB-1,
      are the putative primary degrader of RS in rumen microbial flora and could be
      further studied as probiotic candidates.

PMID- 29654555
TI  - Cost-Effectiveness of Fixed-Dose Combinations Therapies for Chronic Obstructive
      Pulmonary Disease Treatment.
AB  - BACKGROUND AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD), a
      progressive lung disorder associated with decline of respiratory function,
      affects 10.2% of Spanish adults (40-80 years of age). This study aimed to assess
      the cost-effectiveness of two fixed-dose combinations of long-acting muscarinic
      antagonist and long-acting beta2-agonist therapies for COPD, with Spanish
      National Health System perspective. METHODS: A Markov model with five health
      states based on severity levels defined by GOLD 2010 criteria was used to
      simulate in monthly cycles the evolution along a 5-year period of a cohort of
      moderate-to-severe COPD patients, treated with aclidinium-formoterol (ACL/FF)
      400/12 ug or tiotropium-olodaterol (TIO/OLO) 5/5 ug fixed-dose combinations.
      Clinical data on lung-function improvement were obtained from a network meta
      analysis and applied to mean baseline forced-expiratory-volume in 1 s (FEV1) for
      the first 24-weeks period. Natural history for lung-function decline (41 ml/year)
      was applied until the end of simulation. Risk of exacerbation and pneumonia
      occurrence were considered. Pharmaceutical costs were calculated with dosages
      according to indication and public ex-factory prices. The health state-specific
      disease management and event costs, and utilities were derived from the
      literature. Total costs (? 2016) and benefits [life-year-gained (LYG) and quality
      adjusted-life-year (QALY)] were discounted (3.0% yearly). Sensitivity analyses
      were performed. RESULTS: Both therapies provided the same outcomes (4.073 LYG and
      2.928 QALY) at 5-year period. ACL/FF 400/12 ug provided marginally lower costs (?
      - 332) compared to TIO/OLO 5/5 ug. CONCLUSION: ACL/FF 400/12 ug was a cost-saving
      therapy in patients with moderate-to-severe COPD in Spain, and provided
      equivalent effects compared to TIO/OLO 5/5 ug.

PMID- 29654557
TI  - Co-amplification of EBNA-1 and PyLT through dhfr-mediated gene amplification for
      improving foreign protein production in transient gene expression in CHO cells.
AB  - Despite the relatively low transfection efficiency and low specific foreign
      protein productivity (qp) of Chinese hamster ovary (CHO) cell-based transient
      gene expression (TGE) systems, TGE-based recombinant protein production
      technology predominantly employs CHO cells for pre-clinical research and
      development purposes. To improve TGE in CHO cells, Epstein-Barr virus nuclear
      antigen-1 (EBNA-1)/polyoma virus large T antigen (PyLT)-co-amplified recombinant
      CHO (rCHO) cells stably expressing EBNA-1 and PyLT were established using
      dihydrofolate reductase/methotrexate-mediated gene amplification. The level of
      transiently expressed Fc-fusion protein was significantly higher in the EBNA
      1/PyLT-co-amplified pools compared to control cultures. Increased Fc-fusion
      protein production by EBNA-1/PyLT-co-amplification resulted from a higher qp
      attributable to EBNA-1 but not PyLT expression. The qp for TGE-based production
      with EBNA-1/PyLT-co-amplified rCHO cells (EP-amp-20) was approximately 22.9-fold
      that of the control culture with CHO-DG44 cells. Rather than improved
      transfection efficiency, this cell line demonstrated increased levels of mRNA
      expression and replicated DNA, contributing to an increased qp. Furthermore,
      there was no significant difference in N-glycan profiles in Fc-fusion proteins
      produced in the TGE system. Taken together, these results showed that the use of
      rCHO cells with co-amplified expression of the viral elements EBNA-1 and PyLT
      improves TGE-based therapeutic protein production dramatically. Therefore, EBNA
      1/PyLT-co-amplified rCHO cells will likely be useful as host cells in CHO cell
      based TGE systems.

PMID- 29654558
TI  - Now is the time to start routinely using chemical shift imaging in the spine.

PMID- 29654559
TI  - Volumetric dynamic oxygen-enhanced MRI (OE-MRI): comparison with CT Brody score
      and lung function in cystic fibrosis patients.
AB  - OBJECTIVES: To demonstrate, in patients with cystic fibrosis (CF), the
      correlation between three-dimensional dynamic oxygen-enhanced magnetic resonance
      imaging (OE-MRI) measurements and computed tomography Brody score (CF-CT) and
      lung function testing (LFT). METHODS: Twenty-one patients (median age, 25 years;
      female, n = 8) with a range of CF lung disease and five healthy volunteers
      (median age, 31 years; female, n = 2) underwent OE-MRI performed on a 1.5-T MRI
      scanner. Coronal volumes were acquired while patients alternately breathed room
      air and 100% oxygen. Pre-oxygen T1 was measured. Dynamic series of T1-weighted
      volumes were then obtained while breathing oxygen. T1-parameter maps were
      generated and the following OE-MRI parameters were measured: oxygen uptake
      (DeltaPO2max), wash-in time and wash-out time. High-resolution CT and LFT were
      performed. The relationship between CF-CT, LFT and OE-MRI parameters were
      evaluated using Pearson correlation for the whole lung and regionally. RESULTS:
      Mean CF-CT was 24.1+/-17.1. Mean DeltaPO2max and mean wash-in as well as skewness
      of wash-out showed significant correlation with CF-CT (DeltaPO2max: r = -0.741, p
      < 0.001; mean wash-in: r = 0.501, p = 0.017; skewness of wash-out: r = 0.597, p =
      0.001). There was significant correlation for the whole lung and regionally
      between LFT parameters and OE-MR (DeltaPO2max: r = 0.718, p < 0.001; wash-in: r =
      -0.576, p = 0.003; wash-out skewness: r = -0.552, p = 0.004). CONCLUSIONS:
      Functional lung imaging using OE-MRI has the capability to assess the severity of
      CF lung disease and shows a significant correlation with LFT and CF-CT. KEY
      POINTS: * Oxygen-enhanced MRI might play a future role in evaluation and follow
      up of cystic fibrosis. * Heterogeneity of parameter maps reflects localised
      functional impairment in cystic fibrosis. * Avoidance of cumulative radiation
      burden in CF is feasible using OE-MRI.

PMID- 29654560
TI  - Assessment of an advanced virtual monoenergetic reconstruction technique in
      cerebral and cervical angiography with third-generation dual-source CT:
      Feasibility of using low-concentration contrast medium.
AB  - OBJECTIVES: To investigate the feasibility of low-concentration contrast media
      (LC-CM) in cerebral and cervical dual-energy CT angiography (DE-CTA) using an
      advanced monoenergetic (Mono+) reconstruction technique. METHODS: Sixty-five
      consecutive patients prospectively selected to undergo cerebral and cervical DE
      CTA were randomised into two groups: 32 patients (63.7 +/- 9.7 years) in the high
      concentration contrast medium (HC-CM) group with iopromide 370 and 33 patients
      (60.7 +/- 10.8 years) in the low-concentration contrast medium (LC-CM) group with
      iodixanol 270. Traditional monoenergetic (Mono) and Mono+ images from 40 to 100
      keV levels (at 10-keV intervals) and the standard mixed (Mixed, 120 kVp
      equivalent) images were reconstructed. Subjective image quality parameters
      included the contrast-to-noise ratio (CNR) and objective image quality parameters
      were evaluated and compared between the two groups. RESULTS: The 40-keV Mono+
      images in the LC-CM group showed comparable objective CNR (common carotid
      arteries: 83.7 +/- 24.5 vs. 78.1 +/- 23.2; internal carotid arteries: 82.2 +/-
      26.8 vs. 76.8 +/- 24.1; middle cerebral arteries: 72.5 +/- 24.6 vs. 70.6 +/-
      19.2; all p > 0.05) and subjective image scores (3.95 +/- 0.19 vs. 3.83 +/- 0.35;
      p > 0.05) compared with Mixed images in the HC-CM group. CONCLUSION: The Mono+
      reconstruction technique could reduce the concentration of iodinated CM in the
      diagnosis of cerebral and cervical angiography. KEY POINTS: * Mono+ shows
      decreased noise and superior CNR compared with Mono. * The 40-keV Mono+ images
      show the highest CNR in the LC-CM group. * The Mono+ reconstruction technique
      could reduce the concentration of iodinated CM.

PMID- 29654562
TI  - Physical, chemical, and biological properties of white MTA with additions of
      AlF3.
AB  - OBJECTIVES: Addition of aluminum fluoride (AlF3) to MTA was tested to inhibit
      dental discoloration. MATERIALS AND METHODS: MTA Angelus with 0, 5, 15, and 45%
      AlF3 were tested. The set cements were characterized using scanning electron
      microscopy, energy-dispersive spectroscopy, and X-ray diffraction. Radiopacity
      and setting time were analyzed according to ANSI/ADA 57 and ASTM C266-08. Volume
      change was evaluated using volumetric micro-CT analysis. The pH and calcium ion
      release were assessed after 3 and 24 h and 28 days. Dental discoloration in
      contact with the cements was assessed after 24 h and 28 and 90 days of contact
      with bovine and human dentine. Tissue reaction to subcutaneous implantation in
      rats was examined after 30 and 60 days. RESULTS: AlF3 altered the microstructure
      of MTA. The addition of 5% AlF3 did not significantly alter the radiopacity,
      setting time, and volume change (p > 0.05). pH and calcium ion release
      significantly increased with addition of AlF3 (p > 0.05). All the tested
      proportions of AlF3 prevented the dental darkening verified for MTA Angelus in
      bovine and human teeth. AlF3 did not interfere in inflammatory response of MTA in
      all periods of analysis; otherwise, lower amounts showed less intense
      inflammatory infiltrate. CLINICAL RELEVANCE: AlF3 prevents destabilization of
      bismuth oxide and consequent tooth darkening, frequently verified in clinical
      practice when using white MTA. CONCLUSIONS: The use of 5% of AlF3 in combination
      to MTA resulted in a cement that did not result in dental discoloration and did
      not affect significantly physical, chemical, and biological properties.

PMID- 29654561
TI  - Arterial spin-labeling is useful for the diagnosis of residual or recurrent
      meningiomas.
AB  - OBJECTIVES: ASL is useful in evaluating tumour blood flow and in detecting
      hypervascular tumours. The purpose of this study was to assess the additive value
      of ASL to non-contrast and contrast-enhanced (NC/CE)-T1WI for diagnosing residual
      or recurrent meningiomas. METHODS: This retrospective study included 25
      postoperative patients (20 women, 5 men; median age, 65 [32-85] years) with and
      25 gender- and age-matched postoperative patients without residual or recurrent
      meningiomas. ASL was performed using a pseudocontinuous method. Seven independent
      observers (two radiology residents, two general radiologists and three
      neuroradiologists) participated in two reading sessions consisting of only NC/CE
      T1WI (first session) or NC/CE-T1WI with ASL (second session). We evaluated the
      sensitivity and diagnostic performance for the detection of residual or recurrent
      meningiomas. The diagnostic performance was assessed using a figure of merit
      (FOM) calculated via jackknife free-response receiver-operating characteristics.
      Statistical analysis was performed with paired t tests, with a significance level
      of p < .05. RESULTS: The sensitivities were as follows (NC/CE-T1WI vs. NC/CE-T1WI
      with ASL): residents (62.1% vs. 70.7%), general radiologists (75.9% vs. 87.9%),
      neuroradiologists (97.7% vs. 100%) and all observers (81.3% vs. 88.2%). The FOMs
      were as follows (NC/CE-T1WI vs. NC/CE-T1WI with ASL): residents (0.76 vs. 0.83),
      general radiologists (0.83 vs. 0.93), neuroradiologists (0.95 vs. 0.99) and all
      observers (0.86 vs. 0.93). The addition of ASL significantly improved the
      diagnostic parameters for all observers except neuroradiologists (p <. 05).
      CONCLUSIONS: ASL improved the detection rate of residual or recurrent meningiomas
      on NC/CE-T1WI among both radiology residents and general radiologists. KEY
      POINTS: * ASL improved diagnostic performance for residual/recurrent meningioma
      compare to NC/CE-T1WI alone. * Diagnostic sensitivity was increased after adding
      ASL compared with NC/CE-T1WI. * FOM was increased after adding ASL compared with
      NC/CE-T1WI.

PMID- 29654563
TI  - Spectrophotometric analysis of discoloration and internal bleaching after use of
      different antibiotic pastes.
AB  - OBJECTIVES: To investigate teeth's antibiotic-induced color differences after
      bleaching using two different techniques. MATERIALS AND METHODS: One hundred
      twenty extracted maxillar human incisors were examined. The specimens were
      randomly divided into six groups, each receiving one of six antibiotic paste
      fillings: (1) triple antibiotic paste (TAP) with minocycline, (2) double
      antibiotic paste (DAP), (3) TAP with amoxicillin, (4) TAP with cefaclor, (5) TAP
      with doxycycline, and (6) no filling (control group). Spectrophotometric
      measurements were obtained at baseline and then during the first, second, and
      third weeks after paste placement. The specimens discolored by antibiotics pastes
      were randomly divided into two subgroups: (1) internal bleaching with hydrogen
      peroxide (H2O2) and (2) internal bleaching with H2O2 plus Nd-YAG laser
      irradiation. The ?E value was calculated and analyzed using a two-way analysis of
      variance and post-hoc Tukey's test (alpha = 0.05). RESULTS: The ?E for all groups
      showed color differences exceeding the perceptibility threshold (?E ? 3.7) at all
      time points except in the control and DAP groups. Minocycline-induced TAP showed
      the most severe coronal discoloration (32.42). When the ?E was examined,
      thermo/photo bleaching (22.01 +/- 8.23) caused more bleaching than walking
      bleaching (19.73 +/- 5.73) at every time point (P = 0.19). No group returned to
      the original color after bleaching (P < 0.05). CONCLUSIONS: Except for DAP, all
      antibiotic pastes caused discoloration. Internal bleaching with Nd-YAG laser can
      be useful for bleaching/removing this discoloration. CLINICAL RELEVANCE: For
      clinically successful final appearances, understanding the effects of bleaching
      procedures on antibiotic paste discoloration is important.

PMID- 29654564
TI  - Scoping Review and Meta-analysis of Hyperbaric Oxygen Therapy for Radiation
      Induced Hemorrhagic Cystitis.
AB  - PURPOSE OF REVIEW: To critically review and summarize existing literature
      assessing the effectiveness of hyperbaric oxygen therapy (HBOT) for the treatment
      of radiation-induced urologic injury. RECENT FINDINGS: Though 5 of the included
      13 studies were published in the last 2-3 years, the only randomized controlled
      study was performed in 2012. Recent studies have confirmed the safety and
      efficacy of HBOT as well as identified risk factors for success vs. failure of
      HBOT for hemorrhagic radiation cystitis (HRC). Of the 602 patients that received
      HBOT for HRC, 84% had a partial or complete resolution. In the 7 studies that
      utilized RTOG/EORTC, 75% of patients saw an improvement in hematuria of at least
      one grade (out of possible 5 total). Of the 499 patients with documented follow
      up, 14% experienced recurrence, with a median time to recurrence of 10 months (6
      to 16.5 months).

PMID- 29654565
TI  - Perceptions of masculinity and body image in men with prostate cancer: the role
      of exercise.
AB  - PURPOSE: The goal of this study was to explore the association between levels of
      exercise and patterns of masculinity, body image, and quality of life in men
      undergoing diverse treatment protocols for prostate cancer. METHODS: Fifty men
      with prostate cancer (aged 42-86) completed self-report measures. Self-reported
      measures included the following: the Godin Leisure Time Exercise Questionnaire
      (GLTEQ), Masculine Self-esteem Scale (MSES), Personal Attributes Questionnaire
      (PAQ), Body Image Scale (BIS), and the Functional Assessment of Cancer Therapy
      Prostate (FACT-P). Masculinity, body image, and quality of life scores were
      compared between men obtaining recommended levels of exercise (aerobic or
      resistance) and those not obtaining recommended level of exercise. Secondary
      outcomes included the association between masculinity, body image, and quality of
      life scores as they relate to exercise levels. RESULTS: There were significantly
      higher scores of masculinity (p < 0.01), physical well-being (p < 0.05), prostate
      cancer specific well-being (p < 0.05), and overall quality of life (p < 0.05) in
      those obtaining at least 150 min of moderate to vigorous aerobic exercise. In the
      48% of men who had never received androgen deprivation therapy, significantly
      higher levels of masculinity, body image, and quality of life were observed in
      those meeting aerobic guidelines. CONCLUSIONS: Whether treatment includes
      androgen deprivation or not, men who participate in higher levels of aerobic
      exercises report higher levels of masculinity, improved body image, and quality
      of life than those who are inactive. Future longitudinal research is required
      evaluating exercise level and its effect on masculinity and body image.

PMID- 29654566
TI  - Combined aerobic and resistance training improves physical capacity in women
      treated for gynecological cancer.
AB  - PURPOSE: The purpose of this study was to evaluate the effects of 16 weeks
      combined aerobic and resistance training, twice a week, on the physical
      performance in women treated for gynecological cancer. METHODS: Sixty women (56.9
      +/- 13.3 years) who had completed curative treatment for gynecological cancer
      were divided into two groups: a physical training group (PT) (n = 29) or a
      control group (C) (n = 31). The PT group performed two sessions of combined
      aerobic and resistance training weekly for 16 weeks. Peak oxygen consumption
      (VO2peak) and one repetition maximum (1RM) of leg press, leg extension, and chest
      press were measured before group assignment, after 16 weeks and at the 1-year
      follow-up. RESULTS: A significant increase in VO2peak (ml min-1 kg-1) (29.7 +/-
      8.0 vs. 31.3 +/- 8.3, p = .009), leg press (kg) (113.0 +/- 27.3 vs. 116.7 +/-
      29.2, p = .047), leg extension (kg) (44.2 +/- 10.1 vs. 48.0 +/- 10.6, p < .001),
      and chest press (kg) (24.5 +/- 7.5 vs. 26.9 +/- 8.2, p = .001) was seen in the PT
      group from pre- to post-measurement. The PT group maintained the improved aerobic
      condition and muscle strength 1 year after the training intervention. In the C
      group, there were no significant differences between pre- and post-measurements,
      but a significant decrease (28.2 +/- 7.5 vs. 27.0 +/- 7.3, p = .040) in the
      VO2peak from post to 1-year follow-up measurements. CONCLUSIONS: Combined aerobic
      and resistance training twice a week in 16 weeks improves VO2peak and maximal
      strength in women treated for gynecological cancer. The training effects were
      sustained after 1 year in the PT group.

PMID- 29654568
TI  - Application of Bayesian networks in a hierarchical structure for environmental
      risk assessment: a case study of the Gabric Dam, Iran.
AB  - Environmental risk assessment (ERA) is a commonly used, effective tool applied to
      reduce adverse effects of environmental risk factors. In this study, ERA was
      investigated using the Bayesian network (BN) model based on a hierarchical
      structure of variables in an influence diagram (ID). ID facilitated ranking of
      the different alternatives under uncertainty that were then used to evaluate
      comparisons of the different risk factors. BN was used to present a new model for
      ERA applicable to complicated development projects such as dam construction. The
      methodology was applied to the Gabric Dam, in southern Iran. The main
      environmental risk factors in the region, presented by the Gabric Dam, were
      identified based on the Delphi technique and specific features of the study area.
      These included the following: flood, water pollution, earthquake, changes in land
      use, erosion and sedimentation, effects on the population, and ecosensitivity.
      These risk factors were then categorized based on results from the output
      decision node of the BN, including expected utility values for risk factors in
      the decision node. ERA was performed for the Gabric Dam using the analytical
      hierarchy process (AHP) method to compare results of BN modeling with those of
      conventional methods. Results determined that a BN-based hierarchical structure
      to ERA present acceptable and reasonable risk assessment prioritization in
      proposing suitable solutions to reduce environmental risks and can be used as a
      powerful decision support system for evaluating environmental risks.

PMID- 29654569
TI  - Professor Giampaolo Velo 31.4.1943-17.8.2017.

PMID- 29654567
TI  - New Penicillium and Talaromyces species from honey, pollen and nests of stingless
      bees.
AB  - Penicillium and Talaromyces species have a worldwide distribution and are
      isolated from various materials and hosts, including insects and their
      substrates. The aim of this study was to characterize the Penicillium and
      Talaromyces species obtained during a survey of honey, pollen and the inside of
      nests of Melipona scutellaris. A total of 100 isolates were obtained during the
      survey and 82% of those strains belonged to Penicillium and 18% to Talaromyces.
      Identification of these isolates was performed based on phenotypic characters and
      beta-tubulin and ITS sequencing. Twenty-one species were identified in
      Penicillium and six in Talaromyces, including seven new species. These new
      species were studied in detail using a polyphasic approach combining phenotypic,
      molecular and extrolite data. The four new Penicillium species belong to sections
      Sclerotiora (Penicillium fernandesiae sp. nov., Penicillium mellis sp. nov.,
      Penicillium meliponae sp. nov.) and Gracilenta (Penicillium apimei sp. nov.) and
      the three new Talaromyces species to sections Helici (Talaromyces pigmentosus sp.
      nov.), Talaromyces (Talaromyces mycothecae sp. nov.) and Trachyspermi
      (Talaromyces brasiliensis sp. nov.). The invalidly described species Penicillium
      echinulonalgiovense sp. nov. was also isolated during the survey and this species
      is validated here.

PMID- 29654570
TI  - The role of ethylene-vinyl alcohol copolymer in association with other embolic
      agents for the percutaneous and endovascular treatment of type Ia endoleak.
AB  - AIM: To evaluate safety, technical and clinical success of embolization of type
      Ia endoleak (T1a EL) using ethylene-vinyl alcohol copolymer as embolic agent
      alone or in combination with other materials. MATERIALS AND METHODS: Five
      patients presented T1a EL after endovascular repair of aortic aneurysms (EVAR)
      with radiological evidence of expanding sac size; in particular, three had
      contained rupture. In one patient, proximal cuff insertion was previously
      performed, in three patients proximal cuff was urgently inserted but T1a EL
      persisted; one patient, previously treated with Ovation Abdominal Stent Graft
      System, was directly proposed for endovascular treatment. In all cases,
      endovascular embolization was successfully performed and the transfemoral
      approach was always chosen; in one case it failed and translumbar approach by
      direct puncture of the sac was required. Used embolization agents were glue,
      ethylene-vinyl alcohol copolymer (Onyx) and coils in three cases, n-butyl
      cyanoacrylate and Onyx in one case, Onyx and coils in the last case. RESULTS:
      Technical success rate was 100% as well as clinical success. No major or minor
      complication, including non-target embolization, was registered. Clinical success
      was 100% until today and the sac diameter remained stable in four patients and
      decreased in one. CONCLUSIONS: Onyx may be considered a suitable embolic agent in
      the treatment of patients with type Ia endoleaks after EVAR, after failure of
      conventional treatments such as prolonged balloon inflation of the aortic neck or
      deployment of large bare stent.

PMID- 29654571
TI  - The Role of Presepsin Obtained from Tracheal Aspirates in the Diagnosis of Early
      Onset Pneumonia in Intubated Newborns.
AB  - OBJECTIVES: To investigate the role of presepsin obtained from tracheal aspirate
      of intubated newborns in the diagnosis of early neonatal pneumonia. METHODS: A
      cross-sectional observational study was performed on 60 intubated newborns during
      the two-year period. Tracheal aspirate for examination was taken in aseptic
      conditions in usual toilets, by lavage with 2 ml of 0.9% NaCl in Mucus suction
      set. On the same day, presepsin (blood) was measured. RESULTS: There were 34
      newborns in the examined group (with pneumonia) and 26 in the control group.
      Patient groups were similar regarding demographic characteristics related to
      gender and Apgar score. The coefficients of simple linear correlation revealed
      the statistically significant connection between presepsin (from tracheal
      aspirate) and birth body weight, presepsin (plasma), maternal infection and
      pneumonia. Significant differences in the values of presepsin (from tracheal
      aspirate) (p < 0.001) and birth body weight (p = 0.036) were found. CONCLUSIONS:
      In intubated newborns, measurements of presepsin obtained from tracheal aspirate
      suggested that it can be used as a complementary marker in diagnosing early onset
      neonatal pneumonia.

PMID- 29654573
TI  - Correcting "confusability regions" in face morphs.
AB  - The visual system represents summary statistical information from a set of
      similar items, a phenomenon known as ensemble perception. In exploring various
      ensemble domains (e.g., orientation, color, facial expression), researchers have
      often employed the method of continuous report, in which observers select their
      responses from a gradually changing morph sequence. However, given their current
      implementation, some face morphs unintentionally introduce noise into the
      ensemble measurement. Specifically, some facial expressions on the morph wheel
      appear perceptually similar even though they are far apart in stimulus space. For
      instance, in a morph wheel of happy-sad-angry-happy expressions, an expression
      between happy and sad may not be discriminable from an expression between sad and
      angry. Without accounting for this confusability, observer ability will be
      underestimated. In the present experiments we accounted for this by delineating
      the perceptual confusability of morphs of multiple expressions. In a two
      alternative forced choice task, eight observers were asked to discriminate
      between anchor images (36 in total) and all 360 facial expressions on the morph
      wheel. The results were visualized on a "confusability matrix," depicting the
      morphs most likely to be confused for one another. The matrix revealed multiple
      confusable images between distant expressions on the morph wheel. By accounting
      for these "confusability regions," we demonstrated a significant improvement in
      performance estimation on a set of independent ensemble data, suggesting that
      high-level ensemble abilities may be better than has been previously thought. We
      also provide an alternative computational approach that may be used to determine
      potentially confusable stimuli in a given morph space.

PMID- 29654572
TI  - Cardiac Troponin-T as a Marker of Myocardial Dysfunction in Term Neonates with
      Perinatal Asphyxia.
AB  - OBJECTIVES: To describe the diagnostic test properties of Cardiac Troponin-T
      (cTnT) in predicting myocardial dysfunction in asphyxiated term neonates by
      taking echocardiography as the gold standard and to establish the optimum cut-off
      values of cTnT for myocardial dysfunction, shock, severe hypoxic ischemic
      encephalopathy (HIE) and mortality by receiver operator characteristic (ROC)
      curve analysis. METHODS: This was a prospective study based on diagnostic test
      evaluation. The study included 120 term asphyxiated neonates in a tertiary care
      neonatal intensive care unit (NICU) in Southern India from June 2011 through June
      2015. All the neonates were clinically evaluated. Venous blood was taken at 4 h
      of life for cTnT estimation. Echocardiography was done within 24 h of birth.
      RESULTS: The mean cTnT level of asphyxiated term neonates was 0.207+/-0.289 ng/ml
      (mean +/- SD). Asphyxiated neonates with myocardial dysfunction had higher cTnT
      levels (0.277+/-0.231) as compared to those without myocardial dysfunction
      (0.061+/-0.036, p = 0.0001). Using ROC curve, the cut-off cTnT values for
      myocardial dysfunction was 0.1145 ng/ml with sensitivity 92.4% and specificity
      94.1%. Cardiac Troponin-T levels were significantly higher among asphyxiated
      neonates with shock (0.378+/-0.348, p = 0.0001) and the levels also correlated
      positively with increasing grades of HIE. The cut-off cTnT value for mortality
      was 0.2505 ng/ml with sensitivity 83.9% and specificity 96.6%. CONCLUSIONS: In
      asphyxiated term neonates, early cTnT elevation is a marker for predicting
      myocardial dysfunction and elevated cTnT levels had high sensitivity and
      specificity. There was significant relation with increasing cTnT values and
      increasing grades of HIE.

PMID- 29654574
TI  - Evaluation of clinical outcomes following implantation of a sub-2-mm hydrophilic
      acrylic MICS intraocular lens.
AB  - PURPOSE: To evaluate clinical outcomes following sub-2-mm microincision cataract
      surgery (MICS) and intraocular lens (IOL) implantation. SETTING: Five EU clinical
      sites. DESIGN: Prospective, multicenter, open-label, single-arm, non-randomized.
      METHODS: Preoperative assessment involved visual acuity (VA), intraocular
      pressure and biometry measurements. 1.4-mm wound-assisted or 1.8-mm MICS was
      performed. Follow-up visits were made 1 day, 1-2 weeks, 1-2 and 4-6 months after
      surgery. The incision size, corrected distance VA (CDVA), uncorrected distance
      VA, manifest refraction spherical equivalent (MRSE), refraction
      predictability/stability and IOL decentration were assessed. At 12-, 18-, and 24
      month, long-term centration, posterior capsular opacification (PCO) and Nd:YAG
      capsulotomy rates were investigated. RESULTS: A total of 103 eyes were implanted
      with the study IOL (INCISE, Bausch & Lomb), 96 of which were included in visual
      outcome analysis. A mean 6-month CDVA of - 0.02 logMAR (20/20 + 1) was observed
      and 75 eyes (79.8%) and 93 eyes (98.3%) achieved a visual acuity of at least
      20/20 or 20/40. Mean MRSE was - 0.20 +/- 0.60 D. Mean absolute predictive error
      was 0.44 +/- 0.36 D, with 90.4% within 1.00 D of target. Mean total decentration
      was 0.35 +/- 0.36 mm at 6 months and 0.32 +/- 0.14 mm at 24 months (p > 0.05). 24
      month evaluation of posterior capsular opacification score was 0.03 for the
      central area. A Nd:YAG rate of 3.4% was observed at 24 months. CONCLUSIONS: The
      new MICS IOL provided excellent visual outcomes and was safe and effective for
      the sub-2-mm procedure. The MICS IOL demonstrated long-term centration, stability
      and a low rate of PCO development.

PMID- 29654575
TI  - Confocal scanning laser microscopy in patients with postoperative
      endophthalmitis.
AB  - PURPOSE: To investigate alterations of corneal layers in eyes treated for acute
      postoperative endophthalmitis. METHODS: In this retrospective, nonrandomized
      comparative study, eyes treated with 25 gauge pars plana vitrectomy (PPV) for
      acute post-cataract endophthalmitis (group A) were compared to eyes receiving
      uneventful cataract surgery (group B) and uneventful 25 gauge PPV for epiretinal
      membrane (group C). After a minimum follow-up of 8 months from last surgical
      procedure, laser scanning in vivo confocal microscopy (IVCM) was performed.
      RESULTS: Twelve eyes for each group were recruited. Comparing study eyes with
      control eyes of group B and C, no statistical difference was found in corneal
      epithelial cell density (p = n.s.), in density of nerve fibers (p = n.s.), mean
      grade of nerve reflectivity (p = n.s.), mean grade of nerve tortuosity (p =
      n.s.), mean grade of anterior keratocyte activation (p = n.s.), and corneal
      endothelium cell density (p = n.s.), whereas a statistically higher mean grade of
      posterior keratocyte activation was found in group A (p < 0.01). Epithelial and
      endothelial corneal morphologies were graded as regular in all groups. Langerhans
      cells and corneal dendritic-shaped hyper-reflective endothelial deposits were
      found in group A. Both findings were absent in group B and C, and the difference
      was statistically significant (p < 0.01). CONCLUSIONS: IVCM was a useful tool in
      the detection of microscopic chronic corneal abnormalities caused by
      postoperative endophthalmitis. These findings confirmed the presence of a
      subclinical chronic corneal inflammation localized to the posterior stroma that
      should be related to the infectious process. Future studies might clarify
      pathological processes in the acute phase of postoperative endophthalmitis.

PMID- 29654576
TI  - Quantitative evaluation of the tracer distribution in dopamine transporter SPECT
      for objective interpretation.
AB  - PURPOSE: Quantification of the tracer distribution would add objectivity to the
      visual assessments of dopamine transporter (DAT) single photon emission computed
      tomography (SPECT) data. Our study aimed to evaluate the diagnostic utility of
      fractal dimension (FD) as a quantitative indicator of tracer distribution and
      compared with the conventional quantitative value: specific binding ratio (SBR).
      We also evaluated the utility of the combined index SBR/FD (SBR divided by FD).
      MATERIALS AND METHODS: We conducted both clinical and phantom studies. In the
      clinical study, 150 patients including 110 patients with Parkinsonian syndrome
      (PS) and 40 without PS were enrolled. In the phantom study, we used a striatal
      phantom with the striatum chamber divided into two spaces, representing the
      caudate nucleus and putamen. The SBR, FD, and SBR/FD were calculated and compared
      between datasets for evaluating the diagnostic utility. Mann-Whitney test and
      receiver-operating characteristics (ROC) analysis were used for analysis.
      RESULTS: ROC analysis revealed that the FD value had high diagnostic performance
      [the areas under the curve (AUC) = 0.943] and the combined use of SBR and FD
      (SBR/FD) delivered better results than the SBR alone (AUC, 0.964 vs 0.899; p <
      0.001). The sensitivity, specificity, and accuracy, respectively, were 79.1,
      85.0, and 80.7% with SBR, 84.5, 97.5, and 88.0% with FD, and 92.7, 87.5, and
      91.3% with SBR/FD. CONCLUSION: Our results confirmed that the FD value is a
      useful diagnostic index, which reflects the tracer distribution in DAT SPECT
      images. The combined use of SBR and FD was more useful than either used alone.

PMID- 29654577
TI  - Association of the rs1870634 Variant in Long Intergenic Non-protein Coding RNA
      841 with Coronary Artery Disease: A GWAS-Replication Study in an Iranian
      Population.
AB  - Recent genome-wide association studies (GWAS) identified a list of single
      nucleotide polymorphisms (SNPs) associated with coronary artery disease (CAD).
      Replication of GWAS findings in different population corroborated the observed
      association in the parent GWAS. In this study, we aimed to replicate the
      association of rs1870634, a GWAS identified SNP, to CAD in an Iranian population.
      The study population consisted of 267 subjects undergoing coronary angiography
      coronary angiography including 155 CAD patients and 112 non-CAD age- and gender
      matched controls. The genotype determination of rs1870634 SNP performed using
      high-resolution melting analysis (HRM) technique. Our results revealed that the
      GG genotype frequency was significantly higher in CAD patients compared with
      controls (P = 0.03). The results of binary logistic regression suggested that
      this genotype was significantly associated with CAD risk adjustment for age, BMI,
      sex, TC, and LDL-C lipid levels (OR of 2.78, 95% CI (1.10-7.01), P = 0.03).
      Moreover, our results showed that the GG+TG genotypes were 2.52 times more likely
      to develop CAD (95% CI 1.05-6.03) than TT genotype carriers after adjusting for
      age, sex, and lipid profiles (P = 0.037). These data showed that the GG genotype
      could be associated with increased risk of CAD in a sample of Iranian population.

PMID- 29654579
TI  - Metabolic Profiling: Status, Challenges, and Perspective.
AB  - Metabolic profiling has advanced greatly in the past decade and evolved from the
      status of a research topic of a small number of highly specialized laboratories
      to the status of a major field applied by several hundreds of laboratories,
      numerous national centers, and core facilities. The present chapter provides our
      view on the status of the remaining challenges and a perspective of this
      fascinating research area.

PMID- 29654578
TI  - Functional Characterization of Novel Phenylalanine Hydroxylase p.Gln226Lys
      Mutation Revealed Its Non-responsiveness to Tetrahydrobiopterin Treatment in
      Hepatoma Cellular Model.
AB  - Treatment with tetrahydrobiopterin (BH4) is the latest therapeutic option
      approved for patients with phenylketonuria (PKU)-one of the most frequent inborn
      metabolic diseases. PKU or phenylalanine hydroxylase (PAH) deficiency is caused
      by mutations in the PAH gene. Given that some PAH mutations are responsive to BH4
      treatment while others are non-responsive, for every novel mutation that is
      discovered it is essential to confirm its pathogenic effect and to assess its
      responsiveness to a BH4 treatment in vitro, before the drug is administered to
      patients. We found a c.676C>A (p.Gln226Lys) mutation in the PAH gene in two
      unrelated patients with PKU. The corresponding aberrant protein has never been
      functionally characterized in vitro and its response to BH4 treatment is unknown.
      Computational analyses proposed that glutamine at position 226 is an important,
      evolutionary conserved amino acid while the substitution with lysine probably
      disturbs tertiary protein structure and impacts posttranslational PAH
      modifications. Using hepatoma cellular model, we demonstrated that the amount of
      mutant p.Gln226Lys PAH detected by Western blot was only 1.2% in comparison to
      wild-type PAH. The addition of sepiapterin, intracellular precursor of BH4, did
      not increase PAH protein yield thus marking p.Gln226Lys as BH4-non-responsive
      mutation. Therefore, computational, experimental, and clinical data were all in
      accordance showing that p.Gln226Lys is a severe pathogenic PAH mutation. Its non
      responsiveness to BH4 treatment in hepatoma cellular model should be considered
      when deciding treatment options for PKU patients carrying this mutation.
      Consequently, our study will facilitate clinical genetic practice, particularly
      genotype-based stratification of PKU treatment.

PMID- 29654580
TI  - Quality Control and Validation Issues in LC-MS Metabolomics.
AB  - Global metabolic profiling (untargeted metabolomics) of different and complex
      biological matrices aims to implement an holistic, hypothesis-free analysis of
      (potentially) all the metabolites present in the analyzed sample. However, such
      an approach, although it has been the focus of great interest over the past few
      years, still faces many limitations and challenges, particularly with regard to
      the validation and the quality of the obtained results. The present protocol
      describes a quality control (QC) procedure for monitoring the precision of the
      analytical process involving untargeted metabolic phenotyping of urine and
      plasma/serum. The described/suggested methodology can be applied to different
      biological matrices, such as biological biofluids, cell, and tissue extracts.

PMID- 29654581
TI  - Data Treatment for LC-MS Untargeted Analysis.
AB  - Liquid chromatography-mass spectrometry (LC-MS) untargeted experiments require
      complex chemometrics strategies to extract information from the experimental
      data. Here we discuss "data preprocessing", the set of procedures performed on
      the raw data to produce a data matrix which will be the starting point for the
      subsequent statistical analysis. Data preprocessing is a crucial step on the path
      to knowledge extraction, which should be carefully controlled and optimized in
      order to maximize the output of any untargeted metabolomics investigation.

PMID- 29654582
TI  - Bio- and Chemoinformatics Approaches for Metabolomics Data Analysis.
AB  - Metabolomics data analysis includes several repetitive tasks, including data
      sorting, calculation of exact masses or other physicochemical properties, or
      searching for identifiers in different databases. Several of these tasks can be
      automated using command line tools or short scripts in different scripting
      languages like Perl, Python, or R. This chapter presents simple solutions and
      short scripts written in R that can be used for the interaction with specific web
      services or for the calculation of physicochemical properties or molecular
      formulae.

PMID- 29654583
TI  - HILIC-MS/MS Multi-Targeted Method for Metabolomics Applications.
AB  - Metabolomics aims at the identification and quantification of key-end point
      metabolites, basically polar, in order to study changes in biochemical activities
      in response to pathophysiological stimuli or genetic modifications. Targeted
      profiling assays have enjoyed a growing popularity during the last years with LC
      MS/MS as a powerful tool for development of such (semi-) quantitative methods for
      a large number of metabolites. Here we describe a method for absolute
      quantification of ca. 100 metabolites belonging to key metabolite classes such as
      sugars, amino acids, nucleotides, organic acids, and amines with a hydrophilic
      interaction liquid chromatography (HILIC) system comprised of ultra (high)
      performance liquid chromatography (UHPLC) with detection on a triple-quadrupole
      mass spectrometer operating in both positive and negative electrospray ionization
      modes.

PMID- 29654584
TI  - Ion Pair Chromatography for Endogenous Metabolites LC-MS Analysis in Tissue
      Samples Following Targeted Acquisition.
AB  - A protocol for the preparation of tissue extracts for the targeted analysis of
      ca. 150 polar metabolites, including those involved in central carbon metabolism
      is described, using a reversed-phase ion pair U(H)PLC-MS method. Data collection
      enabled by multiple-reaction monitoring provides highly specific, sensitive
      acquisition of metabolic intermediates with a wide range of physicochemical
      properties and pathway coverage. Technical aspects are discussed for method
      transfer along with the basic principles of sample sequence setup, data analysis,
      and validation. General comments are given to help the assessment of data quality
      and system performance.

PMID- 29654585
TI  - LC-MS Untargeted Analysis.
AB  - LC-MS untargeted analysis is a valuable tool in the field of metabolic profiling
      (metabonomics/metabolomics), and the applications of this technology have grown
      rapidly over the past decade. LC-MS offers advantages over other analytical
      platforms such as speed, sensitivity, relative ease of sample preparation, and
      large dynamic range. As with any analytical approach, there are still drawbacks
      and challenges to overcome, but advances are constantly being made regarding both
      column chemistries and instrumentation. There are numerous untargeted LC-MS
      approaches which can be used in this ever-growing research field; these can be
      optimized depending on sample type and the nature of the study or biological
      question. Some of the main LC-MS approaches for the untargeted analysis of
      biological samples will be described in detail in the following protocol.

PMID- 29654586
TI  - NMR-Based Metabolic Profiling Procedures for Biofluids and Cell and Tissue
      Extracts.
AB  - Metabolomic studies offer a wealth of information on cells, tissues, and
      biofluids. The phenotype representation through the metabolic profiling is a
      valuable tool for direct diagnosis, therapeutic strategies, and system's biology
      studies. Nuclear magnetic resonance (NMR) spectroscopy provides a nondestructive
      and extremely reproducible method allowing simultaneous detection of a large
      number of known and unknown chemical substances.Sample collection and preparation
      and experimental conditions are critical for the reliability of the subsequent
      analysis. The pre-analytical phase is decisive as it could generate biased
      spectral data misleading the following analysis. The formulation of standard
      operating procedures is thus of crucial importance in order to access meaningful
      samples and results. In this protocol, we provide standardized operations and
      routine procedures from sample preparation to determine the measurement details
      for the acquisition of NMR spectra highlighting major methodological issues.

PMID- 29654587
TI  - Untargeted GC-MS Metabolomics.
AB  - Untargeted metabolomics refers to the high-throughput analysis of the metabolic
      state of a biological system (e.g., tissue, biological fluid, cell culture) based
      on the concentration profile of all measurable free low molecular weight
      metabolites. Gas chromatography-mass spectrometry (GC-MS), being a highly
      sensitive and high-throughput analytical platform, has been proven a useful tool
      for untargeted studies of primary metabolism in a variety of applications. As an
      omic analysis, GC-MS metabolomics is a multistep procedure; thus, standardization
      of an untargeted GC-MS metabolomics protocol requires the integrated optimization
      of pre-analytical, analytical, and computational steps. The main difference of GC
      MS metabolomics compared to other metabolomics analytical platforms, including
      liquid chromatography-MS, is the need for the derivatization of the metabolite
      extracts into volatile and thermally stable derivatives, the latter being
      quantified in the metabolic profiles. This analytical step requires special care
      in the optimization of the untargeted GC-MS metabolomics experimental protocol.
      Moreover, both the derivatization of the original sample and the compound
      fragmentation that takes place in GC-MS impose specialized GC-MS metabolomic data
      identification, quantification, normalization and filtering methods. In this
      chapter, we describe the integrated protocol of untargeted GC-MS metabolomics
      with both the analytical and computational steps, focusing on the GC-MS specific
      parts, and provide details on any sample depending differences.

PMID- 29654588
TI  - Rat Fecal Metabolomics-Based Analysis.
AB  - Fecal metabolomics-based analysis indisputably constitutes a very useful tool for
      elucidating the biochemistry of digestion and absorption of the gastrointestinal
      system. Fecal samples represent the most suitable, non-invasive, specimen for the
      study of the symbiotic relationship between the host and the intestinal
      microbiota.It is well established that the balance of the intestinal microbiota
      changes in response to some stimuli, physiological such as gender, age, diet,
      exercise and pathological such as gastrointestinal and hepatic disease. Fecal
      samples have been analyzed using the most widespread analytical techniques,
      namely, NMR spectroscopy, GC-MS, and LC-MS/MS. Rat fecal sample is a frequently
      used and particularly useful substrate for metabolomics-based studies in related
      fields. The complexity and diversity of the nature of fecal samples require
      careful and skillful handling for the effective quantitative extraction of the
      metabolites while avoiding their deterioration. Parameters such as the fecal
      sample weight to extraction solvent volume, the nature and the pH value of the
      extraction solvent, and the homogenization process are some important factors for
      the optimal extraction of samples, in order to obtain high-quality metabolic
      fingerprints, using either untargeted or targeted metabolomics.

PMID- 29654589
TI  - GC-MS Metabolomic Profiling of Protic Metabolites Following Heptafluorobutyl
      Chloroformate Mediated Dispersive Liquid Microextraction Sample Preparation
      Protocol.
AB  - A simple analytical workflow is described for gas chromatographic-mass
      spectrometry (GC-MS)-based metabolomic profiling of protic metabolites,
      particularly amino-carboxylic species in biological matrices. The sample
      preparation is carried out directly in aqueous samples and uses simultaneous in
      situ heptafluorobutyl chloroformate (HFBCF) derivatization and dispersive liquid
      liquid microextraction (DLLME), followed by GC-MS analysis in single-ion
      monitoring (SIM) mode. The protocol involves ten simple pipetting steps and
      provides quantitative analysis of 132 metabolites by using two internal
      standards. A comment on each analytical step and explaining notes are provided
      with particular attention to the GC-MS analysis of 112 physiological metabolites
      in human urine.

PMID- 29654590
TI  - Sheathless Capillary Electrophoresis-Mass Spectrometry for the Profiling of
      Charged Metabolites in Biological Samples.
AB  - Capillary electrophoresis (CE) is well suited for the profiling of highly polar
      and charged metabolites as compounds are separated on the basis of their charge
      to-size ratio. The protocol presented here is based on using a recently developed
      sheathless interfacing design, i.e., a porous tip interface, for coupling CE to
      electrospray ionization mass spectrometry (MS). It is demonstrated that
      sheathless CE-MS employing a bare fused-silica capillary at low-pH separation
      conditions can be used for the profiling of both cationic and anionic metabolites
      by only switching the MS detection and electrophoretic separation voltage
      polarity. The proposed sheathless CE-MS protocol allows efficient and sensitive
      profiles to be obtained for a broad array of charged metabolites, including amino
      acids, organic acids, nucleotides, and sugar phosphates, in various biological
      samples, such as urine and extracts of the glioblastoma cell line.

PMID- 29654591
TI  - Two-Phase Extraction for Comprehensive Analysis of the Plant Metabolome by NMR.
AB  - Metabolomics is the area of research, which strives to obtain complete metabolic
      fingerprints, to detect differences between them, and to provide hypothesis to
      explain those differences [1]. But obtaining complete metabolic fingerprints is
      not an easy task. Metabolite extraction is a key step during this process, and
      much research has been devoted to finding the best solvent mixture to extract as
      much metabolites as possible.Here a procedure is described for analysis of both
      polar and apolar metabolites using a two-phase extraction system. D2O and CDCl3
      are the solvents of choice, and their major advantage is that, for the
      identification of the compounds, standard databases can be used because D2O and
      CDCl3 are the solvents most commonly used for pure compound NMR spectra. The
      procedure enables the absolute quantification of components via the addition of
      suitable internal standards. The extracts are also suitable for further analysis
      with other systems like LC-MS or GC-MS.

PMID- 29654593
TI  - Direct Injection Analysis of Fruit VOCs by PTR-ToF-MS: The Apple Case Study.
AB  - The instrumental characterization of volatile organic compounds (VOCs) is
      essential to have a precise, reliable, and reproducible estimation of food aroma
      and, therefore, of the overall product quality. In this report, we introduce four
      analytical approaches based on PTR-MS (proton transfer reaction-mass
      spectrometry) technology suitable to fully investigate the complexity of apple
      aroma. In our opinion, these proposed methodologies can be applied, with slight
      modification, to every kind of fruit for destructive and nondestructive rapid VOC
      fingerprinting.

PMID- 29654592
TI  - NMR Spectroscopy Protocols for Food Metabolomics Applications.
AB  - NMR spectroscopy has become an indispensable tool for the metabolic profiling of
      foods and food products. In the present protocol, we report an analytical
      approach based on liquid-state NMR for the determination of polar and nonpolar
      metabolites in some common liquid (wine, spirits, juice) and solid (cheese,
      coffee, honey) foods. Although the diversity of foods precludes the use of a
      single protocol, with small modifications, the proposed methodologies can be
      adapted to a broader range of foodstuffs.

PMID- 29654594
TI  - LC-MS Untargeted Protocol for the Analysis of Wine.
AB  - This chapter describes a protocol for the analysis of the metabolomic fingerprint
      of wine by liquid chromatography-mass spectrometry. The straightforward,
      optimized sample preparation procedure is limited to a single-step dilution with
      water or acetonitrile. The separation of wine analytes is carried out by two
      columns with orthogonal selectivity, including both reversed-phase (C18) and
      hydrophilic interaction (HILIC) chromatography, while the detection is assured by
      a high-resolution quadrupole time-of-flight mass spectrometer operating in
      negative and positive electrospray ionization mode, in order to obtain four
      different chromatograms for each sample. This validated protocol, or parts of it,
      could be applied in several oenological topic experimental designs, including
      wine quality and wine authenticity.

PMID- 29654595
TI  - Tissue Multiplatform-Based Metabolomics/Metabonomics for Enhanced Metabolome
      Coverage.
AB  - The use of tissue as a matrix to elucidate disease pathology or explore
      intervention comes with several advantages. It allows investigation of the target
      alteration directly at the focal location and facilitates the detection of
      molecules that could become elusive after secretion into biofluids. However,
      tissue metabolomics/metabonomics comes with challenges not encountered in
      biofluid analyses. Furthermore, tissue heterogeneity does not allow for tissue
      aliquoting. Here we describe a multiplatform, multi-method workflow which enables
      metabolic profiling analysis of tissue samples, while it can deliver enhanced
      metabolome coverage. After applying a dual consecutive extraction (organic
      followed by aqueous), tissue extracts are analyzed by reversed-phase (RP-) and
      hydrophilic interaction liquid chromatography (HILIC-) ultra-performance liquid
      chromatography coupled to mass spectrometry (UPLC-MS) and nuclear magnetic
      resonance (NMR) spectroscopy. This pipeline incorporates the required quality
      control features, enhances versatility, allows provisional aliquoting of tissue
      extracts for future guided analyses, expands the range of metabolites robustly
      detected, and supports data integration. It has been successfully employed for
      the analysis of a wide range of tissue types.

PMID- 29654596
TI  - UHPLC-HRMS Analysis for Steroid Profiling in Serum (Steroidomics).
AB  - The extraction and untargeted UHPLC-HRMS analysis of endogenous steroids in serum
      samples is described in this protocol. The employed full-scan acquisition mode
      provides the adequate sensitivity to highlight the main endogenous steroids
      present in blood, including mineralocorticoids, progestogens , and androgens.
      Technical aspects for both chromatography and mass spectrometry are discussed in
      detail, together with a proposition of setup for sample sequence and data
      analysis. Furthermore, general comments are given to help the assessment of data
      quality and system performance.

PMID- 29654597
TI  - Metabolomics in Human Acute-Exercise Trials: Study Design and Preparation.
AB  - Metabolomics can be of great value in the study of exercise metabolism. However,
      because of the high intraindividual and interindividual biological variability of
      the human metabolome, special considerations should be taken into account when
      designing an acute-exercise metabolomic study. To study different exercise
      parameters, e.g., different exercise modes, intensities, etc., a crossover study
      design, where each participant acts as their own control, is preferable to a
      parallel design, one involving different groups of participants. Moreover, the
      study should include a no exercise, control trial. Before each trial,
      participants should follow carefully designed preparatory steps to control for
      possible confounding factors, i.e., maintain repeatable and constant conditions
      for all individual trials of the study to minimize variation due to factors other
      than the one(s) being studied. This chapter focuses on the design of human
      metabolomic studies, where the intervention is an acute metabolic challenge, such
      as an exercise bout or a test meal, and presents some basic steps for screening
      potential participants, performing preliminary tests, preparing for the trial
      day, and performing the trial.

PMID- 29654599
TI  - Gender identity disparities in Pap test use in a sample of binary and non-binary
      transmasculine adults.

PMID- 29654600
TI  - Addressing social determinants of health in an ambulatory setting: quasi
      experimental controlled study of a curricular intervention for residents.

PMID- 29654601
TI  - Gender Differences in the Consequences of Divorce: A Study of Multiple Outcomes.
AB  - In this study, I examined gender differences in the consequences of divorce by
      tracing annual change in 20 outcome measures covering four domains: economic,
      housing and domestic, health and well-being, and social. I used data from the
      German Socio-Economic Panel Study (SOEP) and fixed-effects panel regression
      models on a sample of N = 18,030 individuals initially observed in a marital
      union, N = 1,220 of whom divorced across the observation period (1984-2015).
      Three main findings emerged from the analysis. First, men were more vulnerable to
      short-term consequences of divorce for subjective measures of well-being, but
      postdivorce adaptation alleviated gender differences in these outcomes. Second, a
      medium-term view on multiple outcomes showed more similarity than differences
      between women and men. The medium-term consequences of divorce were similar in
      terms of subjective economic well-being; mental health, physical health, and
      psychological well-being; residential moves, homeownership, and satisfaction with
      housework; and chances of repartnering, social integration with friends and
      relatives, and feelings of loneliness. Third, the key domain in which large and
      persistent gender differences emerged were women's disproportionate losses in
      household income and associated increases in their risk of poverty and single
      parenting. Taken together, these findings suggest that men's disproportionate
      strain of divorce is transient, whereas women's is chronic.

PMID- 29654603
TI  - Anatomy of equine incisors: Pulp horns and subocclusal dentine thickness.
AB  - BACKGROUND: Equine incisors are often reduced in height during corrective dental
      procedures. Increased knowledge of subocclusal dentine thickness and pulp
      morphology may help prevent iatrogenic pulpar exposure. Although such data exist
      for equine cheek teeth, there are currently no reliable data for incisors.
      OBJECTIVES: To measure the distances between pulp cavities and the occlusal as
      well as the labial surfaces of equine incisors and to test if these distances
      change with age. Furthermore, pulp morphology with regard to number and
      orientation of pulp horns was investigated. STUDY DESIGN: Observational study
      using cadaver material and high-resolution computed tomography. METHODS: Upper
      and lower incisor arcades were removed from heads of 13 horses and scanned with
      high-resolution computed tomography. 3D Models were reconstructed and
      configuration as well as number of the pulp horns was evaluated. Anatomical
      marker points were set to measure distances between the pulp horn tips and the
      labial and occlusal surfaces. RESULTS: Subocclusal dentine thickness ranged
      between 1.5 and 11.7 mm in upper and 0.7 and 6.7 mm in lower incisors. It
      decreased with tooth age. Distance to labial aspect ranged between 3.5 and 9.0 mm
      in upper and 3.8 and 8.1 mm in lower incisors and increased with tooth age. MAIN
      LIMITATIONS: Details of horse management, feeding and previous dental care were
      not available. Therefore, it remains unknown how these factors influenced the
      results. CONCLUSIONS: Although mean subocclusal dentine thickness of greater than
      4.1 mm was found, equine incisors occasionally have less than 1 mm of thickness
      with potential for iatrogenic pulpar exposure during incisor reduction.
      Therefore, great care should be exercised by any practitioner during incisor
      reduction.

PMID- 29654602
TI  - A genome wide association study identifies new genes potentially associated with
      eyelid sagging.
AB  - Sagging eyelid is considered as an outward of skin ageing and may cause medical
      issues. However, little is known about the factors involved in sagging eyelid.
      The study, which aims at determining genetic risk factors for eyelid sagging, was
      conducted in a cohort of 502 unrelated Caucasian women living in the Paris
      region. All included participants were aged between 44 and 70 years old (mean
      age, 57.6 years old). The severity of sagging eyelid was graded in 6 categories
      by a dermatologist using standardized photographs of the face. A genome wide
      association study adjusted on potential risk factors (including age and smoking
      habits) was conducted to identify genetic associations. Two single nucleotide
      polymorphisms in total linkage disequilibrium on chromosome 10, rs16927253 (P =
      7.07 * 10-10 ) and rs4746957 (P = 1.06 * 10-8 ), were significantly associated
      with eyelid sagging severity. The rs16927253-T and rs4746957-A alleles showed a
      dominant protective effect towards eyelid sagging. These polymorphisms are
      located in intronic parts of the H2AFY2 gene which encodes a member of the H2A
      histone family and very close to the AIFM2 gene that induces apoptosis.
      Additionally, single nucleotide polymorphisms with a false discovery rate below
      0.25 were located nearby the type XIII collagen COL13A1 gene on chromosome 10 and
      in the ADAMTS18 gene on chromosome 16. Several relevant genes were identified by
      the genome wide association study for their potential role in the sagging eyelid
      severity.

PMID- 29654604
TI  - Facile Synthesis of Highly Efficient Amorphous Mn-MIL-100 Catalysts: Formation
      Mechanism and Structure Changes during Application in CO Oxidation.
AB  - A comprehensive study was carried out on amorphous metal-organic frameworks Mn
      MIL-100 as efficient catalysts for CO oxidation. This study focused on explaining
      the crystalline-amorphous-crystalline transformations during thermolysis of Mn
      MIL-100 and studying the structure changes during the CO oxidation reaction. A
      possible formation mechanism of amorphous Mn-MIL-100 was proposed. Amorphous Mn
      MIL-100 obtained by calcination at 250  degrees C (a-Mn-250) showed a smaller
      specific surface area (4 m2  g-1 ) but high catalytic activity. Furthermore, the
      structure of amorphous Mn-MIL-100 was labile during the reaction. When a-Mn-250
      was treated with reaction atmosphere at high temperature (giving used-a-Mn-250
      S), the amorphous catalysts transformed into Mn2 O3 . Meanwhile, the BET surface
      area (164 m2  g-1 ) and catalytic performance both sharply increased. In
      addition, used-a-Mn-250-S catalyst transformed from Mn2 O3 into Mn3 O4 , and this
      resulted in a slight decrease of catalytic activity in the presence of 1 vol %
      water vapor in the feed stream. A schematic mechanism of the structure changes
      during the reaction process was proposed. The success of the synthesis relies on
      the increase in BET surface area by using CO as retreatment atmosphere, and the
      enhanced catalytic activity was attributed to the unique structure, a large
      quantity of surface active oxygen species, oxygen vacancies, and good low
      temperature reduction behavior.

PMID- 29654605
TI  - Maximization of calcium and phosphate in neonatal total parenteral nutrition.
AB  - BACKGROUND: Appropriate calcium and phosphate supplementation is essential for
      bone growth in preterm infants. Using Rehabix-K2TM (AY Pharmaceuticals, Tokyo,
      Japan) and Pleamin-P InjectionTM (Fuso Pharmaceutical Industries, Osaka, Japan)
      as the total parenteral nutrition (TPN) and amino acid solution, respectively, we
      investigated ways of maximizing calcium and phosphate in the TPN solution.
      METHODS: Rehabix-K2, Pleamin-P, calcium gluconate, sodium phosphate, 50% glucose,
      and water were mixed in varying proportions to create 16 formulations.
      Precipitation assessment was done three times for each of the 16 formulations,
      and was based on the Japanese Pharmacopeia. RESULT: Precipitation was observed 24
      h after mixing when the calcium and phosphate were 60 mEq/L and 30 mmol/L or 80
      mEq/L and 40 mmol/L, respectively. No precipitation was observed when the calcium
      and phosphate were 20 mEq/L and 10 mmol/L, respectively. Precipitation was
      observed once out of three times, when the calcium and phosphate were 40 mEq/L
      and 20 mmol/L, respectively, and the amino acids were 2% and 3% (mean pH, 6.13
      and 6.26, respectively). No precipitation was observed, however, when the calcium
      and phosphate were 40 mEq/L and 20 mmol/L, respectively, and the amino acids were
      0% and 1% (mean pH, 5.88 and 6.05, respectively). CONCLUSION: Not only the
      concentration of calcium and phosphate, but also the pH of the TPN solution, are
      crucial factors for precipitation. Based on these results, a well-balanced TPN
      solution maximizing calcium and phosphate availability will be able to be
      formulated.

PMID- 29654606
TI  - Pharmacokinetics of cefquinome in crucian carp (Carassius auratus gibelio) after
      oral, intramuscular, intraperitoneal, and bath administration.
AB  - The pharmacokinetics (PK) of cefquinome (CEQ) was studied in crucian carp
      (Carassius auratus gibelio) after single oral, intramuscular (i.m.), and
      intraperitoneal (i.p.) administration at a dose of 10 mg/kg body weight and
      following incubation in a 5 mg/L bath for 5 hr at 25 degrees C. The plasma
      concentration of CEQ was determined using high-performance liquid chromatography
      (HPLC). PK parameters were calculated based on mean CEQ concentration using
      WinNonlin 6.1 software. The disposition of CEQ following oral, i.m., or i.p.
      administration was best described by a two-compartment open model with first
      order absorption. After oral, i.m., and i.p. administration, the maximum plasma
      concentration (Cmax ) values were 1.52, 40.53, and 67.87 MUg/ml obtained at 0.25,
      0.23, and 0.35 hr, respectively, while the elimination half-life (T1/2beta )
      values were 4.68, 7.39, and 6.88 hr, respectively; the area under the
      concentration-time curve (AUC) values were 8.61, 339.11, and 495.06 MUg hr/ml,
      respectively. No CEQ was detected in the plasma after bath incubation.
      Therapeutic blood concentrations of CEQ can be achieved in the crucian carp
      following i.m. and i.p. administration at a dosage of 10 mg/kg once every 2 days.

PMID- 29654607
TI  - Hydraulic redistribution affects modeled carbon cycling via soil microbial
      activity and suppressed fire.
AB  - Hydraulic redistribution (HR) of water from moist to drier soils, through plant
      roots, occurs world-wide in seasonally dry ecosystems. Although the influence of
      HR on landscape hydrology and plant water use has been amply demonstrated, HR's
      effects on microbe-controlled processes sensitive to soil moisture, including
      carbon and nutrient cycling at ecosystem scales, remain difficult to observe in
      the field and have not been integrated into a predictive framework. We
      incorporated a representation of HR into the Community Land Model (CLM4.5) and
      found the new model improved predictions of water, energy, and system-scale
      carbon fluxes observed by eddy covariance at four seasonally dry yet ecologically
      diverse temperate and tropical AmeriFlux sites. Modeled plant productivity and
      microbial activities were differentially stimulated by upward HR, resulting at
      times in increased plant demand outstripping increased nutrient supply. Modeled
      plant productivity and microbial activities were diminished by downward HR.
      Overall, inclusion of HR tended to increase modeled annual ecosystem uptake of
      CO2 (or reduce annual CO2 release to the atmosphere). Moreover, engagement of
      CLM4.5's ground-truthed fire module indicated that though HR increased modeled
      fuel load at all four sites, upward HR also moistened surface soil and hydrated
      vegetation sufficiently to limit the modeled spread of dry season fire and
      concomitant very large CO2 emissions to the atmosphere. Historically, fire has
      been a dominant ecological force in many seasonally dry ecosystems, and
      intensification of soil drought and altered precipitation regimes are expected
      for seasonally dry ecosystems in the future. HR may play an increasingly
      important role mitigating development of extreme soil water potential gradients
      and associated limitations on plant and soil microbial activities, and may
      inhibit the spread of fire in seasonally dry ecosystems.

PMID- 29654608
TI  - Neuromuscular blocking agents induced anaphylaxis: Results and trends of a French
      pharmacovigilance survey from 2000 to 2012.
AB  - BACKGROUND: Perioperative anaphylaxis mainly involves neuromuscular blocking
      agents (NMBAs) with an IgE-mediated mechanism. In France, this life-threatening
      condition is reported by anesthetists and allergologists, and two safety alerts
      concerning suxamethonium were raised in 2011 and 2012. This led to start a
      national survey over the 2000-2012 period which objectives were to provide a
      descriptive analysis, to estimate incidence rates, and to analyze the trends over
      this period. METHODS: The French pharmacovigilance database was retrospectively
      queried for all the available NMBAs. Anaphylaxis cases with elevated tryptase and
      positive skin tests were qualified as "confirmed cases." Subgroup analysis
      compared atracurium and cisatracurium vs suxamethonium and rocuronium. RESULTS: A
      total of 680 confirmed cases and 944 nonconfirmed cases were identified.
      Suxamethonium was the most implied NMBA (64%). Incidence rates (according to
      sales data) of suxamethonium and rocuronium were, respectively, 10- and 13-folds
      higher than those of the others NMBAs, regardless the confirmed/nonconfirmed
      status. Cisatracurium incidence rates remained stable over the period, while
      suxamethonium and atracurium increased and rocuronium first decreased but re
      increased after 2006. Male patients were more frequent in the subgroup
      "atracurium-cisatracurium" (P = .019), whereas obesity and emergency setting were
      more frequent in the subgroup "rocuronium-suxamethonium." Shared characteristics
      were the poorly documented previous exposure to NMBA(s) and an insufficient
      adherence of patients to perform skin tests, showing the need to improve this
      procedure. CONCLUSION: Suxamethonium and rocuronium are markedly more involved in
      perioperative anaphylaxis than the other available NMBAs. Patients should be more
      informed about their perioperative anaphylaxis and its consequences.

PMID- 29654609
TI  - A study of the environmental survival of Streptococcus equi subspecies equi.
AB  - BACKGROUND: Streptococcus equi represents a common hazard to equids worldwide.
      Environmental contamination with bacteria shed from an infected horse may
      represent a significant source of contagion and further knowledge of ex vivo
      bacterial survival under different conditions is important for disinfection and
      isolation protocols. OBJECTIVES: To determine the potential duration of survival
      and vigour of growth of S. equi inoculated onto surfaces relevant to equine
      veterinary practice and stabling in summer and winter. STUDY DESIGN: Repeat
      sampling of environmental inocula of S. equi. METHODS: Cultures of S. equi were
      inoculated onto wood, a shoe sole, cotton overalls, inside a nasogastric tube,
      inside a dental rasp, in a wet plastic bucket and onto a fence post both in the
      summer and winter seasons. Frequent resampling and culture from the inoculated
      sites was conducted until no viable bacteria were found. Bacterial viability was
      determined by both duration (time to first negative culture) and vigour of growth
      (growth score over the first 3 days of culture) and compared between inoculated
      sites and times of year. RESULTS: Bacterial viability was enhanced by a wet local
      environment and by the winter season. Survival tended to be short in the summer
      (up to 9 days in wet sites and up to 2 days in dry sites) but much longer in the
      winter (up to 34 days in wet sites and up to 13 days in dry sites). Vigour of
      bacterial growth was also greater in the winter than in the summer as judged by 3
      day-growth scores. MAIN LIMITATIONS: Direct comparison with the variable size and
      nature of naturally shed infectious material is difficult. CONCLUSIONS:
      Veterinarians and personnel handling horses should be aware that S. equi may
      survive in an equine environment for longer than previously found, especially
      when protected by wet and cold conditions.

PMID- 29654610
TI  - Urinary fibrin/fibrinogen degradation products measured using an anti-fibrinogen
      antibody predict orthostatic proteinuria.
AB  - BACKGROUND: To assess the diagnostic value of urinary fibrin/fibrinogen
      degradation products (uFDP) measured using an anti-fibrinogen antibody in
      patients with orthostatic proteinuria (OP), and their use in differentiating
      between OP and glomerulonephritis (GN). METHODS: uFDP levels were measured in the
      first morning (supine) and during a hospital visit (upright) and then normalized
      to urine creatinine levels (uFDP/Cr, ng/mgCr). We compared (i) OP patients
      (n=16); (ii) those in remission for nephrotic syndrome (NS group, n=14) and GN
      (IgA nephropathy: IgAN, n=14; Henoch-Schonlein purpura nephritis: HSPN, n=12);
      and (iii) those with active GN (IgAN, n=12; HSPN, n=19). RESULTS: The uFDP/Cr
      ratio increased from supine to upright urine in patients with OP (P<0.001), but
      decreased in one case. uFDP was excreted in supine urine in 94% of OP cases, with
      no excretion in NS cases or in 92% of cases in GN remission (P<0.001 for both).
      The uFDP/Cr ratio in supine urine was comparable between OP and active GN cases
      (P=0.40), whereas proteinuria in supine urine of all OP patients was in the
      normal range, but was significantly higher in OP cases in upright urine
      (P<0.001). The urinary protein-creatinine ratio was significantly lower in
      patients with OP than in those with active GN in upright urine (P=0.005). A 1108
      ng/mgCr cutoff for the uFDP/Cr ratio in upright urine correctly differentiated OP
      from active GN, with a sensitivity of 87.5% and a specificity of 100%.
      CONCLUSION: Comparison of uFDP levels in supine/upright urine can be reliable for
      diagnosing OP and differentiating it from active GN. This article is protected by
      copyright. All rights reserved.

PMID- 29654611
TI  - Free-Standing Air Cathodes Based on 3D Hierarchically Porous Carbon Membranes:
      Kinetic Overpotential of Continuous Macropores in Li-O2 Batteries.
AB  - Free-standing macroporous air electrodes with enhanced interfacial contact, rapid
      mass transport, and tailored deposition space for large amounts of Li2 O2 are
      essential for improving the rate performance of Li-O2 batteries. An ordered
      mesoporous carbon membrane with continuous macroporous channels was prepared by
      inversely topological transformation from ZnO nanorod array. Utilized as a free
      standing air cathode for Li-O2 battery, the hierarchically porous carbon membrane
      shows superior rate performance. However, the increased cross-sectional area of
      the continuous macropores on the cathode surface leads to a kinetic overpotential
      with large voltage hysteresis and linear voltage variation against Butler-Volmer
      behavior. The kinetics were investigated based on the rate-determining step of
      second electron transfer accompanied by migration of Li+ in solid or quasi-solid
      intermediates. These discoveries shed light on the design of the air cathode for
      Li-O2 batteries with high-rate performance.

PMID- 29654612
TI  - Conserving rare species can have high opportunity costs for common species.
AB  - Conservation practitioners face difficult choices in apportioning limited
      resources between rare species (to ensure their existence) and common species (to
      ensure their abundance and ecosystem contributions). We quantified the
      opportunity costs of conserving rare species of migratory fishes in the context
      of removing dams and retrofitting road culverts across 1,883 tributaries of the
      North American Great Lakes. Our optimization models show that maximizing total
      habitat gains across species can be very efficient in terms of benefits achieved
      per dollar spent, but disproportionately benefits common species. Conservation
      approaches that target rare species, or that ensure some benefits for every
      species (i.e., complementarity) enable strategic allocation of resources among
      species but reduce aggregate habitat gains. Thus, small habitat gains for the
      rarest species necessarily come at the expense of more than 20 times as much
      habitat for common ones. These opportunity costs are likely to occur in many
      ecosystems because range limits and conservation costs often vary widely among
      species. Given that common species worldwide are declining more rapidly than rare
      ones within major taxa, our findings provide incentive for triage among multiple
      worthy conservation targets.

PMID- 29654613
TI  - Incidence and associations of painful neuroma in a contemporary cohort of lower
      limb amputees.
AB  - BACKGROUND: The painful post amputation neuroma significantly impairs the
      prosthesis-wearing lower-limb amputee. It remains poorly understood, with
      literature limited to cohorts of traumatic amputees. This paper reports the
      incidence and associations of painful neuroma in a modern tertiary centre with a
      case load of amputations performed for both traumatic and non-traumatic
      indications. METHOD: This retrospective cohort study analysed the records of 304
      patients who underwent all-cause lower-limb amputation at The Alfred Hospital
      between January 2002 and March 2012. Patients were included in our analysis if
      they completed 1-year follow-up at our Amputee Rehabilitation Clinic, producing a
      final cohort of 96 patients. In order to identify a painful neuroma post
      operatively, both clinical suspicion, and either histopathological or
      radiological evidence were required. RESULTS: The overall incidence of
      symptomatic neuromas was 4.17%. There was no significant difference between
      patients who underwent amputation for a traumatic indication (6.25% (2/32) versus
      3.13% (2/64); P = 0.59) compared to non-traumatic indication (P = 0.59). Visual
      analogue score at discharge and the presence of phantom limb pain at follow-up
      showed significant associations with the formation of painful neuroma. Dose of
      opioid on discharge, history of depression and current smoking did not reach
      statistical significance. CONCLUSION: This study presents a lower incidence of
      painful post-amputation neuroma to those published in the literature. This may be
      attributed to improved methodology. The described associations require further
      investigation into central factors leading to neuroma sensitization.

PMID- 29654614
TI  - Quercetin protects against chronic prostatitis in rat model through NF-kappaB and
      MAPK signaling pathways.
AB  - BACKGROUND: Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is a
      common disease of urology, of which the pathogenesis and therapy remain to be
      further elucidated. Quercetin has been reported to improve the symptoms of
      CP/CPPS patients. We aimed to verify the therapeutic effect of quercetin on
      CP/CPPS and identify the mechanism responsible for it. METHODS: A novel CP/CPPS
      model induced with Complete Freund Adjuvant in Sprague Dawley rats was
      established and the prostates and blood specimens were harvested for further
      measurement after oral administration of quercetin for 4 weeks. RESULTS:
      Increased prostate index and infiltration of lymphocytes, up-regulated expression
      of IL-1beta, IL-2, IL-6, IL-17A, MCP1, and TNFalpha, decreased T-SOD, CAT, GSH
      PX, and increased MDA, enhanced phosphorylation of NF-kappaB, P38, ERK1/2, and
      SAPK/JNK were detected in CP/CPPS rat model. Quercetin was identified to
      ameliorate the histo-pathologic changes, decrease the expression of pro
      inflammatory cytokines IL-1beta, IL-2, IL-6, IL-17A, MCP1, and TNFalpha, improve
      anti-oxidant capacity, and suppress the phosphorylation of NF-kappaB and MAPKs.
      CONCLUSIONS: Quercetin has specific protective effect on CP/CPPS, which is
      mediated by anti-inflammation, anti-oxidation, and at least partly through NF
      kappaB and MAPK signaling pathways.

PMID- 29654615
TI  - Predictors of 1-year mortality after transcatheter aortic valve replacement.
AB  - OBJECTIVE: To identify variables predictive of increased mortality within 1 year
      of transcatheter aortic valve replacement (TAVR). METHODS: We retrospectively
      reviewed the records of 723 consecutive patients who received TAVR from November
      2008 through April 2016. Patient and procedure-related characteristics were
      analyzed with logistic regression for an association with death within 1 year of
      TAVR. RESULTS: Patient mean age was 81 +/- 9 years, male sex was present in 428
      patients (59%), and STS predicted risk of mortality was 9.2 +/- 6.2%. There were
      107 deaths (15%) within 1 year of operation. Multivariable analysis identified
      increased risk of death with severe chronic lung disease (odds ratio [OR] 2.01;
      95% confidence interval [CI] 1.23-3.29; P = 0.006), severe tricuspid valve
      regurgitation (OR 2.35; 95%CI 1.17-4.30; P = 0.017), vascular injury (OR 2.23;
      95%CI 1.15-4.30; P = 0.017), and new-onset dialysis (OR 8.49; 95%CI 3.00-24.03; P
      < 0.001) (Area under the curve 0.687). When stratified by arterial access, there
      was increased risk of death following severe tricuspid valve regurgitation,
      vascular injury, or new-onset dialysis for transfemoral access and severe chronic
      lung disease or new-onset dialysis for alternative access. CONCLUSION: Patient
      characteristics and procedure-related complications are both significantly
      associated with increased risk of death within 1 year of TAVR. Patients with the
      baseline findings of severe chronic lung disease or severe tricuspid valve
      regurgitation may not experience mortality benefit from TAVR, and they should be
      assessed and counselled accordingly. Avoiding procedure-related complications is
      paramount to a good outcome. The findings have important implications for health
      care delivery services.

PMID- 29654616
TI  - Evaluation of digital cryotherapy using a commercially available sleeve style ice
      boot in healthy horses and horses receiving i.v. endotoxin.
AB  - BACKGROUND: Continuous digital cryotherapy experimentally prevents development
      and reduces severity of sepsis-associated laminitis. A sleeve style ice boot
      where ice is in direct contact with the skin, and water drains from the boot is
      being used clinically for distal limb cryotherapy. The degree of cooling achieved
      by this boot is unknown. OBJECTIVES: Evaluate skin and lamellar cooling after
      application of the ice sleeve in healthy horses, and the same horses during an
      endotoxaemia model. STUDY DESIGN: Prospective study, crossover design. METHODS:
      In eight healthy horses thermocouples were inserted into dorsal lamellae of both
      front feet, and under skin on both metacarpi. One forelimb received cryotherapy
      using sleeve style ice boot, with contralateral limb as control. Temperature was
      recorded on data logging devices at 5 min intervals during each cryotherapy
      session. Day 1: temperature data was collected for healthy horses. Day 2: data
      was collected for the same horses during i.v. administration of endotoxin.
      RESULTS: In healthy and endotoxaemic horses, the sleeve style ice boot
      significantly decreased mean skin (7.2 degrees C and 5.8 degrees C respectively)
      and lamellar (10.8 degrees C and 9.6 degrees C respectively) temperatures
      compared with control limbs (P<0.001). Skin and lamellar temperatures in
      endotoxaemic horses undergoing cryotherapy were significantly colder than in
      healthy horses (P = 0.01). MAIN LIMITATIONS: Order of treatment not randomised.
      CONCLUSIONS: The boot caused significant decreases in lamellar temperatures
      compared with untreated control limbs in all horses. Endotoxaemic horses had
      significantly colder lamellae and skin than healthy horses. This study is the
      first to show that a sleeve style boot, where ice does not cover the hoof, can
      cause significant decreases in lamellar temperatures through cooling of blood as
      it travels to the foot.

PMID- 29654617
TI  - Lipidomics for translational skin research: A primer for the uninitiated.
AB  - Healthy skin depends on a unique lipid profile to form a barrier that confers
      protection and prevents excessive water loss, aids cell-cell communication and
      regulates cutaneous homoeostasis and inflammation. Alterations in the cutaneous
      lipid profile can have severe consequences for skin health and have been
      implicated in numerous inflammatory skin conditions. Thus, skin lipidomics is
      increasingly of interest, and recent developments in mass spectrometry-based
      analytical technologies can deliver in-depth investigation of cutaneous lipids,
      providing insight into their role and mechanism of action. The choice of tissue
      sampling technique and analytical approach depends on the location and chemistry
      of the lipid of interest. Lipidomics can be conducted by various mass
      spectrometry approaches, including different chromatography and ionisation
      techniques. Targeted mass spectrometry is a sensitive approach for measuring low
      abundance signalling lipids, such as eicosanoids, endocannabinoids and ceramides.
      This approach requires specific extraction, chromatography and mass spectrometry
      protocols to quantitate the lipid targets. Untargeted mass spectrometry reveals
      global changes and allows analysis of hundreds of complex lipids across a range
      of lipid classes, including phospholipids, glycerophospholipids, cholesteryl
      esters and sphingolipids. Mass spectrometry lipid imaging, including matrix
      assisted laser desorption ionisation mass spectrometry and desorption
      electrospray ionisation mass spectrometry, can reveal information about abundance
      and anatomical distribution of lipids within a single skin sample. Skin
      lipidomics can provide qualitative and quantitative data on hundreds of
      biologically relevant lipid species with different properties and activities, all
      found within a single skin sample, and support translational studies exploring
      the involvement of lipids in skin health and disease.

PMID- 29654618
TI  - Investigation of carryover effect of prior fibre consumption on growth, serum and
      tissue metabolic markers in Ossabaw pigs fed a high-fat diet.
AB  - Carryover effect of prior fibre consumption on metabolic markers was
      investigated. Treatments were arranged in 2 * 2 factorial with 2 fibre sources,
      4% inulin or cellulose (Solka-Floc(r)) and fat levels (5 or 15%) for the low-fat
      diet (LFD) and high-fat diet (HFD) respectively. Pigs were fed the two fibre
      diets for the first 56d (nursery phase), and thereafter fed either the LFD or HFD
      containing no added fibre source from d56 to 140 (growing phase). Pigs on the HFD
      were heavier (p = .05) than those on LF (64.61 vs. 68.38 kg), regardless of prior
      fibre type consumed. Pigs that were fed cellulose during the nursery and later
      fed the HFD had the highest ADG (p < .05). Feeding the HFD resulted in higher
      back fat (BF) (13.41 and 18.18 +/- 0.12 mm for LFD and HFD, respectively; p <
      .01). The HFD resulted in higher (p < .01) insulin (0.014 and 0.016 +/- 0.001
      mg/L for LF and HF respectively) and glucose (100.89 and 125.03 +/- 4.39 mg/dl
      for LF and HF respectively) concentrations in the serum. Inulin increased (p <=
      .02) jejunal expression of SREBP-1c and CL-4, but reduced (p < .05) TNFalpha and
      IL-6 expression in the ileum. Alpha-diversity was significantly different (p <
      .05) between the inulin and cellulose fed pigs at the end of the nursery and
      finishing phases. Therefore, inulin feeding before a HFD may lead to reduction in
      ADG and inflammatory markers in the small intestine of pigs, and thus prevent
      future metabolic disorders.

PMID- 29654619
TI  - Overexpression of ZAKbeta in human osteosarcoma cells enhances ZAKalpha
      expression, resulting in a synergistic apoptotic effect.
AB  - : ZAK is a novel mixed lineage kinase-like protein that contains a leucine-zipper
      and a sterile-alpha motif as a protein-protein interaction domain, and it is
      located in the cytoplasm. There are 2 alternatively spliced forms of ZAK:
      ZAKalpha and ZAKbeta. Previous studies showed that ZAKalpha is involved in
      various cell processes, including cell proliferation, cell differentiation, and
      cardiac hypertrophy, but the molecular mechanism of ZAKbeta is not yet known. In
      a recent study in our laboratory, we found that ZAKbeta can ameliorate the
      apoptotic effect induced by ZAKalpha in H9c2 cells. We further hypothesized that
      ZAKbeta could also improve the apoptotic effect induced by ZAKalpha in human
      osteosarcoma cells. The results of this study show that ZAKbeta can induce
      apoptosis and decrease cell viability similar to the effects of ZAKalpha.
      Interestingly, our ZAKalpha-specific inhibitor assay shows that the expression of
      ZAKbeta is highly dependent on ZAKalpha expression. However, ZAKbeta expression
      effectively induces ZAKalpha expression and results in synergistic enhancement of
      apoptosis in human osteosarcoma cells. Furthermore, co-immunoprecipitation
      results revealed that ZAKalpha can directly interact with ZAKbeta, and this
      interaction may contribute to the enhanced apoptotic effects. SIGNIFICANCE OF THE
      STUDY: ZAK is a mixed lineage kinase involved in cell differentiation,
      proliferation, and hypertrophic growth. ZAKalpha isoform of ZAK is associated
      with tumorigenesis, but the function of ZAKbeta is not yet known. In H9c2 cells,
      ZAKbeta was found to ameliorate the apoptotic effect induced by ZAKalpha.
      However, in osteosarcoma cells, ZAKbeta elevates the apoptotic effect induced by
      ZAKalpha. In this study, we show that similar to ZAKalpha, the ZAKbeta induces
      apoptosis and decreases cell viability. Interestingly, the expression of ZAKbeta
      is dependent on ZAKalpha expression, and ZAKbeta further enhances ZAKalpha
      expression and results in synergistic enhancement of apoptosis in osteosarcoma
      cells.

PMID- 29654620
TI  - Digestive proteases and in vitro protein digestibility of feed ingredients for
      the Central American river turtle, Dermatemys mawii.
AB  - Functional characteristics of digestive proteases and in vitro digestibility of
      several protein sources were studied in hatchlings of Central American river
      turtles, Dermatemys mawii. Acidic and alkaline proteases from the stomach and
      intestines were used, and optimums for acidic proteases were registered at 55
      degrees C and pH 2, while alkaline proteases were found at 55 degrees C and pH 9.
      Ten protein ingredients, both vegetable and animal sources, were explored by the
      pH-STAT method, only for alkaline proteases. The degree of hydrolysis was at its
      highest for squid meal and lowest for blood meal, while the total free amino
      acids level was at its highest for squid meal, and lowest for wheat gluten meal.
      Our results indicate that D. mawii has a broad capacity to digest both animal and
      vegetable sources, and suggests some ingredients more suitable to design
      artificial diets for this species.

PMID- 29654621
TI  - Prenatal predictors of neonatal intensive care unit admission due to respiratory
      distress.
AB  - BACKGROUND: Admission to the neonatal intensive care unit (NICU) due to
      respiratory distress is determined according to subjective clinician judgement.
      We investigated prenatal factors predictive of NICU admission in neonates with
      respiratory distress. METHODS: This case-control study was conducted at Nara
      Prefecture General Medical Center, Nara, Japan, from February 2013 to April 2017
      and included neonates with birthweight >=2,000 g, >=36 weeks of gestational age,
      who required oxygen due to respiratory distress at birth. The cases consisted of
      neonates admitted to the NICU, and the control group consisted of neonates who
      did not require NICU admission. Perinatal factors between the groups were
      compared, and multivariate logistic regression analysis carried out to evaluate
      predictive factors. RESULTS: The NICU group consisted of 94 neonates, and the
      control group, 417 neonates during the period reviewed. On multivariate analysis,
      maternal anemia (OR, 2.97; 95%CI: 1.42-6.21), infertility treatment (OR, 2.79;
      95%CI: 1.36-5.71), threatened preterm labor (OR, 2.16; 95%CI: 1.10-4.23),
      premature rupture of membranes (OR, 5.30, 95%CI: 2.52-11.17), fibroids (OR, 6.06;
      95%CI: 1.57-23.41), history of uterine surgery (OR, 3.53, 95%CI: 1.13-11.06),
      abruptio placentae (OR, 10.21; 95%CI: 1.83-57.17), intrauterine growth
      restriction (OR, 6.69; 95%CI: 1.96-22.85), and having twins (OR, 0.23; 95%CI:
      0.09-0.58) were significant prenatal predictors of NICU admission. CONCLUSION:
      Factors that potentially predict NICU admission were identified. Clinicians may
      wish to consider these factors when treating neonates with respiratory distress.

PMID- 29654622
TI  - Costal Margin Tenderness and the Risk for Intraabdominal Injuries in Children
      With Blunt Abdominal Trauma.
AB  - BACKGROUND: The risk of radiation exposure from computed tomography (CT) imaging
      in children is well recognized. Patient history and physical examination
      findings, including costal margin tenderness (CMT), influence a physician's
      decision to image a child with blunt torso trauma. The objective of this study
      was to determine the importance of CMT for identifying children with
      intraabdominal injuries (IAI) found on CT and IAI undergoing acute intervention.
      METHODS: We conducted an analysis of the Pediatric Emergency Care Applied
      Research Network (PECARN) IAI public use data set, representing a large
      prospective multicenter cohort study from May 2007 to January 2010. Isolated CMT
      was defined as CMT without other identified PECARN risk factors for IAI (i.e.,
      abdominal or thoracic wall trauma, abdominal tenderness or pain, decreased breath
      sounds, or vomiting). Logistic regression was used to calculate adjusted odds of
      IAI in children presenting with isolated and nonisolated CMT. Risk differences
      were calculated to estimate the risk of IAI independently attributable to CMT in
      the setting of isolated PECARN risk factors. Finally, CT use among exposure
      groups was estimated to quantify potentially avoidable imaging. RESULTS: Among
      9,174 children with Glasgow Coma Scale scores of 14 or 15 who sustained blunt
      torso trauma, 1,267 (13.8%) had CMT. Among those with CMT, 177 (14.0%) had
      isolated CMT and 1,090 (86.0%) had nonisolated CMT. No children (0/177; 0%, 95%
      confidence interval [CI] = 0.0%-2.1%) with isolated CMT had IAI, compared to
      17.2% (187/1,090; 95% CI = 15.0%-19.5%) of those with nonisolated CMT. The risk
      differences were not statistically significant. 36/177 (20.3%; 95% CI = 14.7%
      27.0%) children with isolated CMT underwent abdominal CT scans. CONCLUSIONS: The
      risk of IAI associated with isolated CMT is minimal. For children with blunt
      abdominal trauma and isolated CMT, abdominal CT scan is of low yield.

PMID- 29654624
TI  - The development of in vitro embryo production in the horse.
AB  - The development of techniques to produce equine embryos in vitro is reviewed with
      specific reference to intracytoplasmic sperm injection (ICSI). Unexplored 50
      years ago, this technology has progressed rapidly in the last 20 years to become
      a commercial reality for the equine breeding industry. Improvements in our
      understanding of oocyte and embryo competence in the horse have been key factors
      in overcoming some of the initial problems associated with ICSI. It is now
      possible to obtain high nuclear maturation and cleavage rates in vitro and the
      most limiting factor, presently, is the low rate of development to the blastocyst
      stage. However, in spite of this, once obtained, these in vitro-derived
      blastocysts can result in pregnancy rates in excess of 60% following transfer.

PMID- 29654623
TI  - An immunologically relevant rodent model demonstrates safety of therapy using a
      tumour-specific IgE.
AB  - BACKGROUND: Designing biologically informative models for assessing the safety of
      novel agents, especially for cancer immunotherapy, carries substantial
      challenges. The choice of an in vivo system for studies on IgE antibodies
      represents a major impediment to their clinical translation, especially with
      respect to class-specific immunological functions and safety. Fcepsilon receptor
      expression and structure are different in humans and mice, so that the murine
      system is not informative when studying human IgE biology. By contrast,
      FcepsilonRI expression and cellular distribution in rats mirror that of humans.
      METHODS: We are developing MOv18 IgE, a human chimeric antibody recognizing the
      tumour-associated antigen folate receptor alpha. We created an immunologically
      congruent surrogate rat model likely to recapitulate human IgE-FcepsilonR
      interactions and engineered a surrogate rat IgE equivalent to MOv18. Employing
      this model, we examined in vivo safety and efficacy of antitumour IgE antibodies.
      RESULTS: In immunocompetent rats, rodent IgE restricted growth of syngeneic
      tumours in the absence of clinical, histopathological or metabolic signs
      associated with obvious toxicity. No physiological or immunological evidence of a
      "cytokine storm" or allergic response was seen, even at 50 mg/kg weekly doses.
      IgE treatment was associated with elevated serum concentrations of TNFalpha, a
      mediator previously linked with IgE-mediated antitumour and antiparasitic
      functions, alongside evidence of substantially elevated tumoural immune cell
      infiltration and immunological pathway activation in tumour-bearing lungs.
      CONCLUSION: Our findings indicate safety of MOv18 IgE, in conjunction with
      efficacy and immune activation, supporting the translation of this therapeutic
      approach to the clinical arena.

PMID- 29654625
TI  - Brazilian artisanal ripened cheeses as sources of proteolytic lactic acid
      bacteria capable of reducing cow milk allergy.
AB  - AIM: The objective was to obtain lactic acid bacteria (LAB) capable of
      hydrolysing immunoreactive proteins in milk, to optimize the hydrolysis, to
      determine the proteolysis kinetics and to test the safety of the best hydrolytic
      strain. METHODS AND RESULTS: Brazilian cheese was used as source of LAB capable
      of hydrolysing main milk allergens. Proteolytic isolates were submitted to RAPD
      PCR for the characterization of clonal diversity. Optimized hydrolysis was strain
      and protein fraction dependent. 16S rDNA sequencing identified three proteolytic
      strains: Enterococcus faecalis VB43, that hydrolysed alphaS1 -, alphaS2 - and
      beta-caseins, alpha-lactalbumin and beta-lactoglobulin (partial hydrolysis), and
      Pediococcus acidilactici VB90 and Weissella viridescens VB111, that caused
      partial hydrolysis of alphaS1 - and alphaS2 -caseins. Enterococcus faecalis VB43
      tested negative for virulence genes asa1, agg, efaA, hyl, esp, cylLL and cylLS
      but positive for genes ace and gelE. Ethylenediamine tetra-acetic acid inhibited
      the proteolysis, indicating that the main proteases of E. faecalis VB43 are
      metalloproteases. CONCLUSION: Brazilian artisanal cheese is a good source of LAB
      capable of hydrolysing allergenic proteins in milk. One isolate (E. faecalis
      VB43) presented outstanding activity against these proteins and lacked most of
      the tested virulence genes. SIGNIFICANCE AND IMPACT OF THE STUDY: Enterococcus
      faecalis VB43 presents good potential for the manufacture of hypoallergenic dairy
      products.

PMID- 29654626
TI  - Effects of enrofloxacin on antioxidant system, microsomal enzymatic activity, and
      proteomics in porcine liver.
AB  - Enrofloxacin (EF) is a widely used fluoroquinolone, usually regarded as a safe
      and effective treatment for bacterial infections. Adverse effects of EF have
      previously been demonstrated in some species, but so far there have been no
      studies looking specifically at the impact of EF on pigs. In this study, three
      different doses of EF (5, 25 and 125 mg kg bw-1 ) were administrated to Bama
      pigs. The results showed that lipid peroxidation of pig liver tissue occurred
      with all EF doses. The 125 mg kg dose of EF induced catalase (CAT) and
      glutathione peroxidase (GSH-px) and increased CYP450 content in pig liver
      microsomes. The activity of microsomal NADPH-cytochrome C reductase (NCCR) was
      elevated at both the 25 and 125 mg kg doses of EF. Microsomal erythromycin N
      demethylase (ERND) and aminopyrin N-demethylase (AND) were inhibited by high
      doses of EF, while aniline-4-hydroxylase (AH) was unaffected. None of the EF
      treatments affected superoxide dismutase (SOD) or cytochrome b5 content.
      Antioxidases and microsomal enzymes may work together to resist the adverse
      effects of EF. Proteomic analysis revealed increased protein expression of
      carboxylesterase (CES) and alpha-enolase (ENO1) in microsomes as a stress
      response to EF. These results provide new information about the adverse effect of
      fluoroquinolones and help guide their usage more effectively in the clinic or
      animal breeding.

PMID- 29654627
TI  - Clinical features of, and association of bladder ultrasound and uroflowmetry
      with, overactive bladder recovery period in children.
AB  - BACKGROUND: Overactive bladder (OAB) is a symptomatic syndrome defined by urinary
      urgency, usually accompanied by increased urination frequency and nocturia, with
      or without urinary incontinence. The prevalence of pediatric OAB in 5-13 year
      olds is as high as 16.6%, but the pathophysiology and epidemiology have not been
      sufficiently elucidated. METHODS: We retrospectively reviewed medical records in
      117 children with OAB aged between 5 and 15 years during the years 2012-2016. At
      initial presentation, abdominal ultrasound and uroflowmetry were performed, and
      behavioral modifications, such as timed voiding, and constipation therapy were
      initiated. If there was no response after 4 weeks, antimuscarinic treatment was
      added. We evaluated the clinical features of OAB and factors related to the
      recovery period, which was defined as the period from the start of behavioral
      modifications to cure. RESULTS: The average recovery period was 11.9 +/- 9.73
      months. There was no significant difference in the recovery period according to
      age, gender, percentage of urination frequency, nocturnal enuresis, or
      constipation. The recovery period was significantly shorter in the group with
      bladder wall thickness >=5 mm than with bladder wall thickness <5 mm. Children
      with a tower-shaped curve on uroflowmetry had a significantly shorter recovery
      period than those with a bell-shaped curve. CONCLUSIONS: Bladder wall thickness
      and uroflow curve shape are related to the recovery period of pediatric OAB.

PMID- 29654628
TI  - Birch pollen-related foods can cause late eczematous reactions in patients with
      atopic dermatitis.
AB  - BACKGROUND: Previous studies have indicated that in patients with atopic
      dermatitis (AD) and birch pollen allergy pollen-related foods are able to cause
      late eczematous response. However, the relevance of AD worsening by ingestion of
      birch pollen-related foods is still a matter of debate. OBJECTIVE: The purpose of
      this retrospective study was to determine how frequently birch pollen-related
      foods induce a deterioration of eczema. Additionally, the diagnostic value of
      specific IgE (sIgE) determination was evaluated. METHODS: A total of 182 children
      and adults with AD and suspected birch pollen-related food allergy underwent 261
      double-blind placebo-controlled food challenges (DBPCFC). Total and sIgE levels
      were determined prior to DBPCFC. RESULTS: Sixty-five patients developed allergic
      reactions (responders) upon DBPCFC with birch pollen-related foods (n = 103
      DBPCFC). Of these, 32 patients exhibited significant deterioration of AD defined
      as a median increase of 15.4 severity scoring of atopic dermatitis index points
      (95% CI 12.4-16.3) from baseline making up 37% of all positive reactions.
      Responders showed significantly higher sIgE levels to birch pollen and apple as
      well as a higher prevalence of allergic rhinoconjunctivitis compared to
      nonresponders (P < .05). However, patients with late eczematous response could
      not be differentiated from those with isolated immediate-type reactions by sIgE
      levels. CONCLUSION: In a subpopulation of patients with AD and birch pollen
      sensitization, related foods should be considered as a trigger for an aggravation
      of eczema. As sufficient markers for prediction of late eczematous reactions are
      still lacking, DBPCFC cannot be replaced in diagnosis of birch pollen-related
      foods in patients with AD. CLINICAL IMPLICATIONS: In patients with AD and birch
      pollen allergy, birch pollen-related foods should be considered as a provocation
      factor for an aggravation of disease signs and symptoms.

PMID- 29654629
TI  - Management of patients with incurable colorectal cancer: a retrospective audit.
AB  - AIM: Counselling patients and their relatives about non-curative management
      options in colorectal cancer is difficult because of a paucity of published data.
      This study aims to determine outcomes in patients unsuitable for curative surgery
      and the rates of subsequent surgical intervention. METHOD: This was an analysis
      of all colorectal cancers managed without curative surgery in a district general
      hospital from a prospectively maintained cancer registry between 2009 and 2016,
      as decided by a multidisciplinary team. Primary outcomes were overall survival
      and secondary outcomes were subsequent intervention rates and impact of tumour
      stage. RESULTS: In all, 183 patients out of 976 patients (18.8%) were identified.
      The median age at diagnosis was 81 years [interquartile range (IQR) 71-87 years].
      Overall median survival from diagnosis was 205 days (IQR 60-532 days). One-year
      mortality was 62.3%. Patients were classified into two groups depending on the
      reason for a non-curable approach: patient-related (PR) or disease-related (DR).
      The difference in survival between PR (median 277 days, IQR 70-593) and DR
      (median 179 days, IQR 51-450) was 98 days (P = 0.023). Twenty-four patients were
      alive at the end of the study period; 19 out of 91 cases in PR (20.8%) and five
      out of 92 cases in DR (5.4%). Overall intervention rates were 11.9%, with higher
      rates in the DR group (P = 0.005). Disease stage was not associated with
      subsequent surgical intervention between the two groups (P = 0.392). CONCLUSION:
      Life expectancy for non-curatively managed patients within our unit was 6.8
      months with one in nine patients requiring subsequent surgical admission for
      palliation. This information may be useful when counselling patients with
      incurable colorectal malignancy.

PMID- 29654630
TI  - Physical activity modifies the FTO effect on BMI change in Japanese adolescents.
AB  - BACKGROUND: Evidence of the effects of fat mass and obesity-associated (FTO) gene
      variation and long-term effects of physical activity (PA) on adiposity in
      adolescents is largely scarce. This study aimed to investigate whether physical
      activity modulates the effects of the FTO gene on body mass index (BMI) changes
      in Japanese adolescents between the ages of 13 and 18 years. METHODS: Data of 343
      subjects (156 boys; 187 girls) who were enrolled in 2006 and 2007 from schools on
      Shunan City, Japan, were collected. Genotyping (rs1558902) was conducted, and
      anthropometric measurements and blood test results were recorded for subjects in
      the eighth grade. A second survey involving self-reporting of anthropometric
      measurements was conducted when the subjects were in the twelfth grade. PA was
      estimated using the International Physical Activity Questionnaire in this survey.
      BMI and the standard deviation score for BMI (BMI-SDS) were calculated. BMI
      changes and BMI-SDS changes were compared among FTO genotypes using a
      multivariate model. RESULTS: The effect of the interaction between PA and the FTO
      genotype on BMI changes was significant among boys but not girls. Among boys, PA
      had a significant negative influence on BMI-SDS changes in those with the AA
      genotype and a significant positive influence on BMI and BMI-SDS changes in those
      with the TT genotype. CONCLUSION: These data suggest that the influence of PA on
      BMI changes and BMI-SDS changes varied on the basis of genotype. PA modified the
      effect of the FTO gene on BMI changes in Japanese boys. This article is protected
      by copyright. All rights reserved.

PMID- 29654631
TI  - Incidence and survival of hematological cancers among adults ages >=75 years.
AB  - Evaluating population-based data of hematologic malignancies (HMs) in older
      adults provides prognostic information for this growing demographic. Incidence
      rates and one- and five-year relative survival rates were examined for specific
      HMs among adults ages >=75 years using data from the Surveillance, Epidemiology
      and End Results (SEER) Program. Hematologic malignancy cases (Hodgkin lymphoma
      (HL), non-Hodgkin lymphoma (NHL), multiple myeloma (MM), acute lymphocytic
      leukemia (ALL), chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML),
      and chronic myeloid leukemia (CML)) were reported to one of 18 SEER registries.
      Recent average annual (2010-2014) incidence rates and incidence trends from 1973
      to 2014 were examined for cases ages >=75 years. One- and five-year relative
      cancer survival rates were examined for adults ages >=75 years diagnosed 2007
      2013, with follow-up into 2014. From 1973 to 2014, incidence rates increased for
      NHL, MM, and AML, decreased for HL, and remained relatively stable for ALL, CLL,
      and CML among adults ages >=75 years. The highest one- and five-year relative
      survival rates were observed among adults with CLL ages 75-84 years (1 year:
      91.8% (95% CI = 91.8-90.8)) and 5 years: 76.5% (95% CI = 74.2-78.6)). The lowest
      one- and five-year survival rates were observed among adults with AML ages 75-84
      (1 year: 18.2% (95% CI = 74.2-78.6) and 5 years: 2.7% (95% CI = 2.0-3.6)).
      Survival for older adults ages >=75 years with HMs is poor, particularly for
      acute leukemia. Understanding the heterogeneity in HM outcomes among older
      patients may help clinicians better address the hematological cancer burden and
      mortality in the aging population.

PMID- 29654632
TI  - Assessment of area spread of porcine reproductive and respiratory syndrome (PRRS)
      virus in three clusters of swine farms.
AB  - Despite decades of porcine reproductive and respiratory syndrome (PRRS) research,
      outbreaks with emerging and re-emerging PRRS virus (PRRSV) strains are not
      uncommon in North America. The role of area spread, commonly referred but not
      limited to airborne transmission, in originating such outbreaks is currently
      unknown. The main objective of this study was to explore the role of area spread
      on the occurrence of new PRRSV cases by combining information on genetic
      similarity among recovered PRRSV isolate's open-reading frame (ORF) 5 sequences
      and publicly available weather data. Three small regions were enrolled in the
      study for which high farm-level participation rate was achieved, and swine sites
      within those regions were readily sampled after reporting of an outbreak in a sow
      farm. Oral fluid PCR testing was used to determine PRRSV status of farms, and
      wind roses were generated for assessment of prevailing wind directions during 2
      14 days preceding the outbreak. Under the conditions of this study, the data did
      not support the area spread theory as the main cause for these outbreaks. We
      suggest that for future studies, analysis of animal movement and other links
      between farms such as personnel, equipment and sharing of service providers
      should be incorporated for better insights on source of the virus. Furthermore,
      the development of rapid and easy diagnostic methods for ruling out resident
      PRRSV is urgently needed.

PMID- 29654633
TI  - Molecular changes during TGFbeta-mediated lung fibroblast-myofibroblast
      differentiation: implication for glucocorticoid resistance.
AB  - Airway remodeling is an important process in response to repetitive inflammatory
      mediated airway wall injuries. This is characterized by profound changes and
      reorganizations at the cellular and molecular levels of the lung tissue. It is of
      particular importance to understand the mechanisms involved in airway remodeling,
      as this is strongly associated with severe asthma leading to devastating airway
      dysfunction. In this study, we have investigated the transforming growth factor
      beta (TGFbeta, a proinflammatory mediator)-activated fibroblast to myofibroblast
      transdifferentiation pathway, which plays a key role in asthma-related airway
      remodeling. We show that TGFbeta induces fibroblast to myofibroblast
      transdifferentiation by the expression of alphaSMA, a specific myofibroblast
      marker. Furthermore, Smad2/Smad3 gene and protein expression patterns are
      different between fibroblasts and myofibroblasts. Such a change in expression
      patterns reveals an important role of these proteins in the cellular phenotype as
      well as their regulation by TGFbeta during cellular transdifferentiation.
      Interestingly, our data show a myofibroblastic TGFbeta-mediated increase in
      glucocorticoid receptor (GR) expression and a preferential localization of GR in
      the nucleus, compared to in fibroblasts. Furthermore, the GRbeta (nonfunctional
      GR isoform) is increased relative to GRalpha (functional isoform) in
      myofibroblasts. These results are interesting as they support the idea of a
      GRbeta-mediated glucocorticoid resistance observed in the severe asthmatic
      population. All together, we provide evidence that key players are involved in
      the TGFbeta-mediated fibroblast to myofibroblast transdifferentiation pathway in
      a human lung fibroblast cell line. These players could be the targets of new
      treatments to limit airway remodeling and reverse glucocorticoid resistance in
      severe asthma.

PMID- 29654635
TI  - Super-quenched Molecular Probe Based on Aggregation-Induced Emission and
      Photoinduced Electron Transfer Mechanisms for Formaldehyde Detection in Human
      Serum.
AB  - Energy transfer between fluorescent dyes and quenchers is widely used in the
      design of light-up probes. Although dual quenchers are more effective in offering
      lower background signals and higher turn-on ratios than one quencher, such probes
      are less explored in practice as they require both quenchers to be within the
      proximity of the fluorescent core. In this contribution, we utilized
      intramolecular motion and photoinduced electron transfer (PET) as quenching
      mechanisms to build super-quenched light-up probes based on fluorogens with
      aggregation-induced emission. The optimized light-up probe possesses negligible
      background and is able to detect not only free formaldehyde (FA) but also
      polymeric FA, with an unprecedented turn-on ratio of >4900. We envision that this
      novel dual quenching strategy will help to develop various light-up probes for
      analyte sensing.

PMID- 29654634
TI  - Measurement of cations, anions, and acetate in serum, urine, cerebrospinal fluid,
      and tissue by ion chromatography.
AB  - Accurate quantification of cations and anions remains a major diagnostic tool in
      understanding diseased states. The current technologies used for these analyses
      are either unable to quantify all ions due to sample size/volume, instrument
      setup/method, or are only able to measure ion concentrations from one
      physiological sample (liquid or solid). Herein, we adapted a common analytical
      chemistry technique, ion chromatography and applied it to measure the
      concentration of cations; sodium, potassium, calcium, and magnesium (Na+ , K+ ,
      Ca2+ , and Mg2+ ) and anions; chloride, and acetate (Cl- , - OAc) from
      physiological samples. Specifically, cations and anions were measured in liquid
      samples: serum, urine, and cerebrospinal fluid, as well as tissue samples: liver,
      cortex, hypothalamus, and amygdala. Serum concentrations of Na+ , K+ , Ca2+ ,
      Mg2+ , Cl- , and - OAc (mmol/L): 138.8 +/- 4.56, 4.05 +/- 0.21, 4.07 +/- 0.26,
      0.98 +/- 0.05, 97.7 +/- 3.42, and 0.23 +/- 0.04, respectively. Cerebrospinal
      fluid concentrations of Na+ , K+ , Ca2+ , Mg2+ , Cl- , and - OAc (mmol/L): 145.1
      +/- 2.81, 2.41 +/- 0.26, 2.18 +/- 0.38, 1.04 +/- 0.11, 120.2 +/- 3.75, 0.21 +/-
      0.05, respectively. Tissue Na+ , K+ , Ca2+ , Mg2+ , Cl- , and - OAc were also
      measured. Validation of the ion chromatography method was established by
      comparing chloride concentration between ion chromatography with a known method
      using an ion selective chloride electrode. These results indicate that ion
      chromatography is a suitable method for the measurement of cations and anions,
      including acetate from various physiological samples.

PMID- 29654636
TI  - Healthy community-living older men differ from women in associations between
      myostatin levels and skeletal muscle mass.
AB  - BACKGROUND: Myostatin is a negative regulator of muscle growth but the
      relationship between serum myostatin levels and muscle mass is unclear. This
      study investigated the association between serum myostatin levels and skeletal
      muscle mass among healthy older community residents in Taiwan, to evaluate the
      potential of serum myostatin as a biomarker for diagnosing sarcopenia and/or
      evaluating the effect of its treatment. METHODS: Study data were excerpted from a
      random subsample of the I-Lan Longitudinal Aging Study population. Serum
      myostatin levels were determined and categorized into tertiles (low, medium,
      high). Relative appendicular skeletal muscle mass (RASM) was calculated as
      appendicular lean body mass by dual-energy X-ray absorptiometry divided by height
      squared (kg/m2 ). Low muscle mass was defined as recommended by the Asian Working
      Group for Sarcopenia. RESULTS: The analytic study sample comprised 463 adults
      (mean age: 69.1 years; 49.5% men). Compared with subjects with normal RASM, those
      with lower RASM were older and frailer, with significantly higher prevalence of
      malnutrition, lower serum dehydroepiandrosterone (DHEA) levels, and were more
      likely to have low serum myostatin status. Multivariable logistic regression
      analysis showed that male sex (OR 3.60, 95% CI 1.30-9.92), malnutrition (OR 4.39,
      95% CI 1.56-12.36), DHEA (OR 0.99, 95% CI 0.99-1.00), and low myostatin (OR 3.23,
      95% CI 1.49-7.01) were all independent risk factors for low RASM (all P < 0.05).
      In men, DHEA (OR 0.99, 95% CI 0.98-1.00) and low myostatin (OR 4.89, 95% CI 1.79
      13.37) were significantly associated with low RASM (both P < 0.05); however, only
      malnutrition was associated with low RASM in women (OR 13.59, 95% CI 2.22-83.25,
      P < 0.05). CONCLUSIONS: Among healthy community-living older adults, low serum
      myostatin levels were associated with low skeletal muscle mass in men, but not in
      women. Our results do not support using serum myostatin levels to diagnose
      sarcopenia, or to monitor how it responds to treatments. Further research is
      needed to understand why men apparently differ from women in the
      interrelationship between their myostatin levels and muscle mass.

PMID- 29654637
TI  - Retrospective detection of Porcine circovirus 3 (PCV-3) in pig serum samples from
      Spain.
AB  - Porcine circovirus 3 (PCV-3) is an emerging circovirus species that has recently
      been reported in different countries around the world, suggesting a widespread
      circulation. In this study, sera samples originating from 654 pigs of different
      production phases and clinical/pathological conditions, submitted for diagnostic
      purposes between 1996 and 2017, were randomly selected. Detection of PCV-3 genome
      in such samples was attempted with a previously described PCR method, and the
      partial genome sequence was obtained from selected PCV-3-positive samples from
      different years. Compiled data confirmed that PCV-3 has been circulating in the
      Spanish pig population since 1996. The overall frequency of PCV-3 PCR-positive
      samples in the study period was 11.47% (75 of 654). Phylogenetic analysis of
      twelve PCV-3 partial sequences obtained showed a high nucleotide identity with
      the already known PCV-3 sequences, with minor variations among years. No
      significant correlation was found between the detection of PCV-3 and any
      production phase nor clinical/pathological condition. These results confirm PCV-3
      circulation at least since 1996 in the Spanish pig population with a low/moderate
      frequency. Although the information obtained was limited, PCV-3 did not appear to
      be linked to any specific pathological condition or age group.

PMID- 29654638
TI  - Diagnosis of oral lichen planus from analysis of saliva samples using terahertz
      time-domain spectroscopy and chemometrics.
AB  - The ability to diagnose oral lichen planus (OLP) based on saliva analysis using
      THz time-domain spectroscopy and chemometrics is discussed. The study involved 30
      patients (2 male and 28 female) with OLP. This group consisted of two subgroups
      with the erosive form of OLP (n  =  15) and with the reticular and papular forms
      of OLP (n  =  15). The control group consisted of six healthy volunteers (one
      male and five females) without inflammation in the mucous membrane in the oral
      cavity and without periodontitis. Principal component analysis was used to reveal
      informative features in the experimental data. The one-versus-one multiclass
      classifier using support vector machine binary classifiers was used. The two
      stage classification approach using several absorption spectra scans for an
      individual saliva sample provided 100% accuracy of differential classification
      between OLP subgroups and control group.

PMID- 29654639
TI  - Analytic Errors in Analysis of Public Health Survey Data Are Avoidable.

PMID- 29654640
TI  - Rochester Epidemiology Project Data Exploration Portal.
AB  - INTRODUCTION: The goal of this project was to develop an interactive, web-based
      tool to explore patterns of prevalence and co-occurrence of diseases using data
      from the expanded Rochester Epidemiology Project (E-REP) medical records-linkage
      system. METHODS: We designed the REP Data Exploration Portal (REP DEP) to include
      summary information for people who lived in a 27-county region of southern
      Minnesota and western Wisconsin on January 1, 2014 (n = 694,506; 61% of the
      entire population). We obtained diagnostic codes of the International
      Classification of Diseases, 9th edition, from the medical records-linkage system
      in 2009 through 2013 (5 years) and grouped them into 717 disease categories. For
      each condition or combination of 2 conditions (dyad), we calculated prevalence by
      dividing the number of persons with a specified condition (numerator) by the
      total number of persons in the population (denominator). We calculated observed
      to-expected ratios (OERs) to test whether 2 conditions co-occur more frequently
      than would co-occur as a result of chance alone. RESULTS: We launched the first
      version of the REP DEP in May 2017. The REP DEP can be accessed at
      http://rochesterproject.org/portal/. Users can select 2 conditions of interest,
      and the REP DEP displays the overall prevalence, age-specific prevalence, and sex
      specific prevalence for each condition and dyad. Also displayed are OERs overall
      and by age and sex and maps of county-specific prevalence of each condition and
      OER. CONCLUSION: The REP DEP draws upon a medical records-linkage system to
      provide an innovative, rapid, interactive, free-of-charge method to examine the
      prevalence and co-occurrence of 717 diseases and conditions in a geographically
      defined population.

PMID- 29654641
TI  - Impact of Early High-protein Diet on Neurofunctional Recovery in Rats with
      Ischemic Stroke.
AB  - BACKGROUND Ischemic stroke, featuring high incidence, morbidity, and mortality,
      is one of the three major diseases troubling human beings. The purpose of the
      study was to examine the impact of early high-protein diet on neurofunctional
      recovery in rats with ischemic stroke as well as their cerebral infarct areas and
      molecular expressions of oxidative stress. MATERIAL AND METHODS The middle
      cerebral artery occlusion model (MCAO) was established, and 48 adult, male
      Sprague Dawley (SD) rats of clean grade aged seven to eight months (250-280 g
      body weight) were randomized into four groups: the MCAO group with high-protein
      diet (MH), the MCAO group with standard-protein diet (MS), the sham group with
      high-protein diet (SH), and the sham group with standard-protein diet (SS). High
      protein diet intervention started on the first day of the surgery, and the rats'
      body weights and their neurological deficit scores were measured on each
      postoperative day while the scores of motors coordination and balance ability
      were recorded every other day. In addition, their cerebral infant areas and the
      molecular expressions of oxidative stress injuries were detected as well. RESULTS
      Compared to the MS group, the rats in the MH group gained faster weight growth
      (p<0.05), presented significantly lower neurological impairment scores (p<0.05),
      remarkably improved motor coordination and balance ability (p<0.05) as well as
      showed smaller cerebral infarct areas (p<0.05), increased expression of SOD
      (superoxide dismutase), and reduced expressions of MDA (malondialdehyde) and iNOS
      (inducible nitric oxide synthase). However, there was no significant difference
      between the SS group and the SH group (p>0.05). CONCLUSIONS Early high-protein
      diet facilitates the recovery of body weights and neurological functions as well
      the reduction of the cerebral infarct areas of rats, thus alleviating ischemic
      stroke-caused oxidative stress injuries.

PMID- 29654642
TI  - Analysis of RDR1/RDR2/RDR6-independent small RNAs in Arabidopsis thaliana
      improves MIRNA annotations and reveals unexplained types of short interfering RNA
      loci.
AB  - Plant small RNAs (sRNAs) modulate key physiological mechanisms through post
      transcriptional and transcriptional silencing of gene expression. Small RNAs fall
      into two major categories: those are reliant on RNA-dependent RNA polymerases
      (RDRs) for biogenesis and those that are not. Known RDR1/2/6-dependent sRNAs
      include phased and repeat-associated short interfering RNAs, while known RDR1/2/6
      independent sRNAs are primarily microRNAs (miRNA) and other hairpin-derived
      sRNAs. In this study we produced and analyzed sRNA-seq libraries from
      rdr1/rdr2/rdr6 triple mutant plants. We found 58 previously annotated miRNA loci
      that were reliant on RDR1, -2, or -6 function, casting doubt on their
      classification. We also found 38 RDR1/2/6-independent sRNA loci that are not
      MIRNAs or otherwise hairpin-derived, and did not fit into other known paradigms
      for sRNA biogenesis. These 38 sRNA-producing loci have as-yet-undescribed
      biogenesis mechanisms, and are frequently located in the vicinity of protein
      coding genes. Altogether, our analysis suggests that these 38 loci represent one
      or more undescribed types of sRNA in Arabidopsis thaliana.

PMID- 29654643
TI  - Is glucagon-like peptide-1 fully protected by the dipeptidyl peptidase 4
      inhibitor sitagliptin when administered to patients with type 2 diabetes?
AB  - AIM: To evaluate the relationship between plasma dipeptidyl-peptidase 4 (DPP-4)
      activity and its protection of glucagon-like peptide-1 (GLP-1) using the DPP-4
      inhibitor sitagliptin. METHODS: On four separate days, patients with type 2
      diabetes (T2D) (n = 8; age: 59.9 +/-10.8 [mean +/-SD] years; body mass index
      [BMI]: 28.8 +/-4.6 kg/m2 ; glycated haemoglobin A1c [HbA1c]: 43.1 +/-0.5 mmol/mol
      [6.6% +/-1.7%]) received a 380-minute continuous intravenous infusion of GLP-1
      (1.0 pmol * kg bodyweight-1  * minutes-1 ) and a double-blind, single-dose oral
      administration of sitagliptin in doses of 0 (placebo), 25, 100 and 200 mg.
      RESULTS: Plasma DPP-4 activity decreased compared to baseline (placebo) with
      increasing doses of sitagliptin (P < .01), reaching a maximal inhibition with the
      100 mg dose. Levels of intact GLP-1 increased with increasing doses of
      sitagliptin from placebo to 100 mg (area under curve [AUC] 7.2 [95%, CI; 12.1,
      16.4] [placebo], 10.7 [16.1, 21.4] [25 mg], 11.7 [17.8, 23.6] [100 mg] nmol/L *
      360 minutes [P < .01]), but no further increase in intact GLP-1 levels was
      observed with 200 mg of sitagliptin (11.5 [17.6, 23.4] nmol/L * 360 minutes) (P =
      .80). CONCLUSION: Our findings suggest that the sitagliptin dose of 100 mg is
      sufficient to inhibit both plasma and membrane-bound DPP-4 activity, presumably
      also leading to complete protection of endogenous GLP-1 in patients with T2D.

PMID- 29654644
TI  - Reciprocal relationships and the importance of feedback in patient and public
      involvement: A mixed methods study.
AB  - BACKGROUND: Reciprocal relationships between researchers and patient and public
      involvement (PPI) contributors can enable successful PPI in research. However,
      research and anecdotal evidence suggest that researchers do not commonly provide
      feedback to PPI contributors thus preventing them from knowing whether, how or
      where their contributions were useful to researchers and research overall. AIMS:
      The aim of this study was to explore the variation, types, importance of, and
      satisfaction with feedback given by researchers to PPI contributors in six PPI
      groups in England, and identify the barriers to the process of feedback. METHODS:
      An explanatory mixed methods sequential study design with a questionnaire survey
      followed by semi-structured interviews with researchers and PPI contributors in
      six PPI groups. PPI contributors were involved in all stages of the research
      process. RESULTS: Researchers do not routinely give feedback to PPI contributors.
      Feedback was found to have different meanings: an acknowledgement, impact and
      study success and progress. PPI contributors who receive feedback are motivated
      for further involvement; it supports their learning and development and prompts
      researchers to reflect on PPI impact. The importance of the role of a PPI lead or
      coordinator to facilitate the process of providing feedback was also highlighted.
      CONCLUSION: This study found no generic way to give feedback indicating that
      mutual feedback expectations should be discussed at the outset. PPI feedback
      needs to become integral to the research process with appropriate time and
      resources allocated. PPI feedback can be seen as a key indicator of mature,
      embedded PPI in research.

PMID- 29654646
TI  - An In Vitro Evaluation of the Effect of Various Adhesives and Surface Treatments
      on Bond Strength of Resin Cement to Polyetheretherketone.
AB  - PURPOSE: To investigate the effect of various surface pretreatments and adhesive
      systems on bond strength of resin cement to polyetheretherketone (PEEK).
      MATERIALS AND METHODS: 360 PEEK specimens were divided into 4 groups to receive
      the following pretreatments (n = 90): no pretreatment, sandblasting, silica
      coating and Er:YAG laser. Surface roughness (SR) and scanning electron microscopy
      (SEM) evaluations were conducted after mechanical pretreatments for topographical
      surface evaluations. After the pretreatments, each group was divided into 3
      subgroups (n = 30) according to the adhesive system used: no adhesive system,
      Visio.link, and Signum PEEK Bond. Resin cement was applied, and specimens
      underwent 5000 thermocycles (5-55 degrees C) before shear bond strength (SBS)
      test. One-way ANOVA and Tukey test were used to analyze the SR data; 2-way ANOVA
      and Fisher's LSD test were used to analyze the SBS data at the confidence
      interval of 95% (alpha = 0.05). RESULTS: The sandblasting group demonstrated the
      highest SR values (p < 0.05). No significant differences in SR values were
      identified among silica coating, laser, and control groups (p ? 0.05).
      Conditioning with Visio.link after sandblasting group exhibited the highest SBS
      values (p < 0.05). No significant differences in SBS values were found between
      laser and control group (p ? 0.05). Conditioned groups presented higher SBS
      values than unconditioned groups (p < 0.05). Between the two adhesive systems,
      Visio.link demonstrated statistically significant higher SBS values than Signum
      PEEK Bond (p < 0.05). CONCLUSION: Silica coating and sandblasting were shown to
      provide superior pretreatment of PEEK surface. Laser pretreatments showed no
      effectiveness on bond strength of resin cement to PEEK. Adhesive systems improved
      the resin bonding to PEEK.

PMID- 29654645
TI  - A randomized trial of adjunct testosterone for cancer-related muscle loss in men
      and women.
AB  - BACKGROUND: Cancer cachexia negatively impacts cancer-related treatment options,
      quality of life, morbidity, and mortality, yet no established therapies exist. We
      investigated the anabolic properties of testosterone to limit the loss of body
      mass in late stage cancer patients undergoing standard of care cancer treatment.
      METHODS: A randomized, double-blind, placebo-controlled phase II clinical trial
      was undertaken to assess the potential therapeutic role of adjunct testosterone
      to limit loss of body mass in patients with squamous cell carcinoma of the cervix
      or head and neck undergoing standard of care treatment including chemotherapy and
      chemoradiation. Patients were randomly assigned in blocks to receive weekly
      injections of either 100 mg testosterone enanthate or placebo for 7 weeks. The
      primary outcome was per cent change in lean body mass, and secondary outcomes
      included assessment of quality of life, tests of physical performance, muscle
      strength, daily activity levels, resting energy expenditure, nutritional intake,
      and overall survival. RESULTS: A total of 28 patients were enrolled, 22 patients
      were studied to completion, and 21 patients were included in the final analysis
      (12 placebo, nine testosterone). Adjunct testosterone increased lean body mass by
      3.2% (95% confidence interval [CI], 0-7%) whereas those receiving placebo lost
      3.3% (95% CI, -7% to 1%, P = 0.015). Although testosterone patients maintained
      more favourable body condition, sustained daily activity levels, and showed
      meaningful improvements in quality of life and physical performance, overall
      survival was similar in both treatment groups. CONCLUSIONS: In patients with
      advanced cancer undergoing the early phase of standard of care therapy, adjunct
      testosterone improved lean body mass and was also associated with increased
      quality of life, and physical activity compared with placebo.

PMID- 29654648
TI  - Photoinducible DRONPA-s: a new tool for investigating cell-cell connectivity.
AB  - The development of multicellular plants relies on the ability of their cells to
      exchange solutes, proteins and signalling compounds through plasmodesmata,
      symplasmic pores in the plant cell wall. The aperture of plasmodesmata is
      regulated in response to developmental cues or external factors such as pathogen
      attack. This regulation enables tight control of symplasmic cell-to-cell
      transport. Here we report on an elegant non-invasive method to quantify the
      passive movement of protein between selected cells even in deeper tissue layers.
      The system is based on the fluorescent protein DRONPA-s, which can be switched on
      and off repeatedly by illumination with different light qualities. Using
      transgenic 35S::DRONPA-s Arabidopsis thaliana and a confocal microscope it was
      possible to activate DRONPA-s fluorescence in selected cells of the root
      meristem. This enabled us to compare movement of DRONPA-s from the activated
      cells into the respective neighbouring cells. Our analyses showed that pericycle
      cells display the highest efflux capacity with a good lateral connectivity. In
      contrast, root cap cells showed the lowest efflux of DRONPA-s. Plasmodesmata of
      quiescent centre cells mediated a stronger efflux into columella cells than into
      stele initials. To simplify measurements of fluorescence intensity in a complex
      tissue we developed software that allows simultaneous analyses of fluorescence
      intensities of several neighbouring cells. Our DRONPA-s system generates
      reproducible data and is a valuable tool for studying symplasmic connectivity.

PMID- 29654647
TI  - Common genetic variants in GAL, GAP43 and NRSN1 and interaction networks confer
      susceptibility to Hirschsprung disease.
AB  - Hirschsprung disease (HSCR) is a severe multifactorial genetic disorder.
      Microarray studies indicated GAL, GAP43 and NRSN1 might contribute to the altered
      risk in HSCR. Thus, we focused on genetic variations in GAL, GAP43 and NRSN1, and
      the gene-gene interactions involved in HSCR susceptibility. We recruited a
      strategy combining case-control study and MassArray system with interaction
      network analysis. For GAL, GAP43 and NRSN1, a total of 18 polymorphisms were
      assessed in 104 subjects with sporadic HSCR and 151 controls of Han Chinese
      origin. We found statistically significant differences between HSCR and control
      groups at 5 genetic variants. For each gene, the haplotypes combining all
      polymorphisms were the most significant. Based on SNPsyn, MDR and GeneMANIA
      analyses, we observed significant gene-gene interactions among GAL, GAP43, NRSN1
      and our previous identified RELN, GABRG2 and PTCH1. Our study for the first time
      indicates that genetic variants within GAL, GAP43 and NRSN1 and related gene-gene
      interaction networks might be involved in the altered susceptibility to HSCR in
      the Han Chinese population, which might shed more light on HSCR pathogenesis.

PMID- 29654649
TI  - Mindful organizing in patients' contributions to primary care medication safety.
AB  - BACKGROUND: There is a need to ensure that the risks associated with medication
      usage in primary health care are controlled. To maintain an understanding of the
      risks, health-care organizations may engage in a process known as "mindful
      organizing." While this is typically conceived of as involving organizational
      members, it may in the health-care context also include patients. Our study aimed
      to examine ways in which patients might contribute to mindful organizing with
      respect to primary care medication safety. METHOD: Qualitative focus groups and
      interviews were carried out with 126 members of the public in North West England
      and the East Midlands. Participants were taking medicines for a long-term health
      condition, were taking several medicines, had previously encountered problems
      with their medication or were caring for another person in any of these
      categories. Participants described their experiences of dealing with medication
      related concerns. The transcripts were analysed using a thematic method. RESULTS:
      We identified 4 themes to explain patient behaviour associated with mindful
      organizing: knowledge about clinical or system issues; artefacts that facilitate
      control of medication risks; communication with health-care professionals; and
      the relationship between patients and the health-care system (in particular,
      mutual trust). CONCLUSIONS: Mindful organizing is potentially useful for framing
      patient involvement in safety, although there are some conceptual and practical
      issues to be addressed before it can be fully exploited in this setting. We have
      identified factors that influence (and are strengthened by) patients' engagement
      in mindful organizing, and as such would be a useful focus of efforts to support
      patient involvement.

PMID- 29654650
TI  - An evaluation of a visual-visual successive matching-to-sample procedure to
      establish equivalence classes in adults.
AB  - Traditionally, behavior analysts have studied stimulus equivalence using a
      matching-to-sample (MTS) preparation. Although researchers have shown the utility
      of MTS to yield equivalence classes, the procedure requires several prerequisite
      skills for a learner to accurately respond. Previous research with humans and
      nonhumans has shown that relational responding can be produced via compound
      stimulus discrimination and successive matching-to-sample (S-MTS). We conducted
      four experiments with college students to further evaluate the effectiveness of S
      MTS in the establishment of stimulus relations. S-MTS trials consisted of the
      presentation of a single sample stimulus followed by one comparison in a fixed
      location on a computer screen. Depending upon the sample-comparison relation,
      participants touched (i.e., go) or did not touch (i.e., no-go) the comparison
      stimulus. Following training of the baseline relations (AB/BC), we assessed the
      emergence of symmetry, transitivity, and equivalence performances (i.e., BA/CB
      and AC/CA). Results support the utility of the S-MTS procedure as a possible
      alternative to traditional MTS. This study has direct implications for
      participants for whom traditional three-array MTS procedures may be challenging.

PMID- 29654651
TI  - Enhanced longevity and metabolism by brown adipose tissue with disruption of the
      regulator of G protein signaling 14.
AB  - Disruption of the regulator for G protein signaling 14 (RGS14) knockout (KO) in
      mice extends their lifespan and has multiple beneficial effects related to
      healthful aging, that is, protection from obesity, as reflected by reduced white
      adipose tissue, protection against cold exposure, and improved metabolism. The
      observed beneficial effects were mediated by improved mitochondrial function. But
      most importantly, the main mechanism responsible for the salutary properties of
      the RGS14 KO involved an increase in brown adipose tissue (BAT), which was
      confirmed by surgical BAT removal and transplantation to wild-type (WT) mice, a
      surgical simulation of a molecular knockout. This technique reversed the
      phenotype of the RGS14 KO and WT, resulting in loss of the improved metabolism
      and protection against cold exposure in RGS14 KO and conferring this protection
      to the WT BAT recipients. Another mechanism mediating the salutary features in
      the RGS14 KO was increased SIRT3. This mechanism was confirmed in the RGS14 X
      SIRT3 double KO, which no longer demonstrated improved metabolism and protection
      against cold exposure. Loss of function of the Caenorhabditis elegans RGS-14
      homolog confirmed the evolutionary conservation of this mechanism. Thus,
      disruption of RGS14 is a model of healthful aging, as it not only enhances
      lifespan, but also protects against obesity and cold exposure and improves
      metabolism with a key mechanism of increased BAT, which, when removed, eliminates
      the features of healthful aging.

PMID- 29654652
TI  - Solidarity and cost management: Swiss citizens' reasons for priorities regarding
      health insurance coverage.
AB  - CONTEXT: Approaches to priority-setting for scarce resources have shifted to
      public deliberation as trade-offs become more difficult. We report results of a
      qualitative analysis of public deliberation in Switzerland, a country with high
      health-care costs, an individual health insurance mandate and a strong tradition
      of direct democracy with frequent votes related to health care. METHODS: We
      adapted the Choosing Healthplans All Together (CHAT) tool, an exercise developed
      to transform complex health-care allocation decisions into easily understandable
      choices, for use in Switzerland. We conducted focus groups in twelve Swiss
      cities, recruiting from a range of socio-economic backgrounds in the three
      language regions. FINDINGS: Participants developed strategic arguments based on
      the importance of basic coverage for all, and of cost-benefit evaluation. They
      also expressed arguments relying on a principle of solidarity, in particular the
      importance of protection for vulnerable groups, and on the importance of medical
      care. They struggled with the place of personal responsibility in coverage
      decisions. In commenting on the exercise, participants found the degree of
      consensus despite differing opinions surprising and valuable. CONCLUSION: The
      Swiss population is particularly attentive to the costs of health care and means
      of reducing these costs. Swiss citizens are capable of making trade-offs and
      setting priorities for complex health issues.

PMID- 29654653
TI  - Identification of four TMC1 variations in different Chinese families with
      hereditary hearing loss.
AB  - BACKGROUND: Variants in TMC1 (transmembrane channel-like 1) can cause both
      autosomal dominant and recessive hearing loss in human population. Mice with Tmc1
      variants have been shown to be ideal animal models for gene therapy. In this
      article, we report four TMC1 variants in four different Chinese families and the
      follow-up auditory phenotype of a previously reported family. METHODS: Four
      families with TMC1 variants, as well as a previously described family with TMC1
      variant orthologous to the Beethoven mouse, were recruited in this study. A
      comprehensive auditory evaluation was performed on all ascertained family
      members. High-throughput sequencing was conducted using genomic DNA from the
      probands and other family members to identify probable deafness genes. RESULTS:
      We identified four TMC1 (NM_138691.2) variations, including two pathogenic
      variants, c.1714G>A, and c.1253T>A, one likely pathogenic variant,
      c.[797T>C];[797T>C], and one single nucleotide polymorphism (SNP), c.2276G>A.
      Among these variants, c.[797T>C];[797T>C] is a novel likely pathogenic variant,
      and c.1714G>A and c.1253T>A are known pathogenic variants at the DFNB7/11
      (DFNA36) locus. Phenotype-genotype correlation analysis of TMC1 variants showed
      that the TMC1 dominant variation-related phenotype was late-onset, progressive,
      high frequency to all frequency sensorineural hearing loss, while the TMC1
      recessive variant was related to congenital all frequency sensorineural hearing
      impairment. CONCLUSIONS: Two pathogenic, one likely pathogenic variants and one
      SNP of TMC1 were identified in four Chinese families with hereditary hearing
      loss, indicating that TMC1 may be a more frequent cause of hearing loss than
      expected. TMC1 variants related to hearing loss result in specific phenotypes.
      The TMC1 c.1253T>A (p.M418K) variation, homologous to the Tmc1 c. 1235 T> A
      (p.M412K) variant in Beethoven mice, was the second report of this variant in
      human patients with hearing loss, suggesting the possibility to translational
      gene therapy from Beethoven mice to human patients.

PMID- 29654654
TI  - Compressed Collagen Enhances Stem Cell Therapy for Corneal Scarring.
AB  - Stem cells from human corneal stroma (CSSC) suppress corneal stromal scarring in
      a mouse wound-healing model and promote regeneration of native transparent tissue
      (PMID:25504883). This study investigated efficacy of compressed collagen gel
      (CCG) as a vehicle to deliver CSSC for corneal therapy. CSSC isolated from limbal
      stroma of human donor corneas were embedded in soluble rat-tendon collagen,
      gelled at 37 degrees C, and partially dehydrated to a thickness of 100 um by
      passive absorption. The CCG disks were dimensionally stable, easy to handle, and
      could be adhered securely to de-epithelialized mouse cornea with fibrin-based
      adhesive. CSSC in CCG maintained >80% viability for >1 week in culture media and
      could be cryopreserved in 20% fetal bovine serum-10%DMSO in liquid nitrogen. CCG
      containing as few as 500 CSSC effectively prevented visible scarring and
      suppressed expression of fibrotic Col3a1 mRNA. CSSC in CCG were more effective at
      blocking scarring on a per-cell basis than CSSC delivered directly in a fibrin
      gel as previously described. Collagen-embedded cells retained the ability to
      suppress corneal scarring after conventional cryopreservation. This study
      demonstrates use of a common biomaterial that can facilitate storage and handling
      of stem cells in a manner that may provide off-the-shelf delivery of stem cells
      as a therapy for corneal scarring. Stem Cells Translational Medicine 2018;7:487
      494.

PMID- 29654655
TI  - Biliary drainage as treatment for allograft steatosis following liver
      transplantation for PFIC-1 disease: A single-center experience.
AB  - Development of macrovesicular steatosis post-LT in patients with PFIC-1 is
      increasingly being observed, with the etiology not fully understood. We highlight
      successful and effective EBD for reversal of allograft steatosis in 2 patients
      with PFIC-1 disease and discuss our experience with internal biliary diversion in
      this patient population.

PMID- 29654656
TI  - Giardia duodenalis in primates: Classification and host specificity based on
      phylogenetic analysis of sequence data.
AB  - Giardia duodenalis colonizes the gastrointestinal tract of a wide range of hosts,
      including humans and other primates. It is grouped into eight different
      Assemblages and, beyond that, into a number of sub-Assemblages, defined ad hoc on
      the basis of genetic differences; these various groups are often considered to be
      associated with a specific restricted host range. The aim of this study was to
      use publicly available genotyping data to investigate the relatedness of human
      and non-human primate (NHP) Giardia isolates in order to evaluate the usefulness
      of current taxonomic classification and to assess whether there is potential for
      zoonotic transmission between humans and NHP. Our final data set consisted of
      sequence data from 165 isolates, 111 from NHP and 54 from humans. Assemblages
      were well defined, but sub-Assemblages across Assemblage B were not resolved.
      Although sub-Assemblages AI and AII were resolved, the terms were not found to
      capture any useful molecular or host/deme properties. In the phylogenetic tree,
      NHP isolates were scattered among human isolates across Assemblages A and B, and
      were even found in Assemblage E. We conclude that there does not appear to be
      significant molecular distinction between human and NHP Giardia isolates across
      these four molecular markers. Thus, on the basis of these markers, we cannot
      exclude a risk for zoonotic and anthropozoonotic transmission of Assemblages A
      and B isolates, irrespective of sub-Assemblage classification. We further
      evaluated the relative merit of the four genes used in genotyping studies. The
      tpi, gdh and bg genes gave relatively congruent tree topologies, but the SSU gene
      did not resolve Assemblages according to the current classification. Future
      genotyping efforts should aim for multilocus or whole-genome approaches and, in
      particular, use of the SSU gene as the sole marker should be avoided when
      possible.

PMID- 29654657
TI  - Hepatoprotective effect of Herpetospermum caudigerum Wall. on carbon
      tetrachloride-induced hepatic fibrosis in rats.
AB  - Tibetan medicine Herpetospermum caudigerum Wall. (HCW) has long been employed to
      treat hepatitis, inflammatory diseases and jaundice according to the records of
      "The Four Medical Tantras" in China. This study was investigated to explore the
      protective effects of HCW on hepatic fibrosis and the possible mechanism in a rat
      model. Hepatic fibrosis was established by intragastric administration of 3 ml/kg
      carbon tetrachloride (CCl4 ) twice a week for 6 weeks. CCl4 -treated rats were
      received HCW (1 and 3 g/kg/d) and silymarin (0.1 g/kg/d) from 3 to 6 weeks. The
      results showed that HCW could significantly decrease the levels of AST, ALT, HA,
      LN, PCIII, Col IV, TNF-alpha, IL-1beta and IL-6. Moreover, HCW could effectively
      inhibit collagen deposition and reduce the pathological damage. Analysis
      experiments finally exhibited that HCW was able to markedly inhibit hepatic
      fibrosis by modulating the expressions of NF-kappaB p65, IkappaBalpha, Samd3 and
      TGF-beta1 proteins. Therefore, our results suggest that HCW has hepatoprotective
      activity against CCl4 -induced hepatic fibrosis in rats by regulating the
      inflammatory responses.

PMID- 29654658
TI  - High incidence of BK virus-associated hemorrhagic cystitis in children after
      second or third allogeneic hematopoietic stem cell transplantation.
AB  - BKV-HC is a serious complication of allogeneic HSCT. To characterize the
      incidence, risk factors, and clinical outcomes of post-HSCT BKV-HC, we
      retrospectively analyzed 112 patients who underwent one or more allogeneic HSCTs
      at our hospital between 2001 and 2017. Twenty underwent second or third HSCT
      thereafter. Ten patients developed BKV-HC at a median of 30 days after HSCT. The
      100-day cumulative incidences of grade 0-4 and grade 2-4 BKV-HC were 7.8% and
      6.2%, respectively. HSCTs performed in 2011-2017 associated with significantly
      higher 100-day cumulative incidence of grade 2-4 BKV-HC (14.0%) than HSCTs
      performed in 2001-2010 (1.3%, P = 0.004). On multivariate analysis, second or
      third HSCT was the only independent significant risk factor for development of
      grade 2-4 BKV-HC (P = 0.015). Serial PCR monitoring of urine and blood BKV load
      did not predict BKV-HC. The recent increase in the incidence of BKV-HC may
      reflect recent innovations in transplant technologies that facilitate second or
      third HSCT, which are known to cause prolonged immune deficiency. If safe and
      effective treatment or prophylaxis becomes available, it could be used to target
      the high-risk patients for BKV-HC.

PMID- 29654659
TI  - Human umbilical cord mesenchymal stem cells facilitate the up-regulation of miR
      153-3p, whereby attenuating MGO-induced peritoneal fibrosis in rats.
AB  - MiRNAs contribute greatly to epithelial to mesenchymal transition (EMT) of
      peritoneal mesothelial cells (PMCs), which is a crucial step in peritoneal
      fibrosis (PF). In this study, we tried to profile whether miRNA expression
      differences exist after human umbilical cord mesenchymal stem cells (hUCMSCs)
      treatment in PF rats and investigate the possible role of miR-153-3p involved in
      anti-EMT process. We randomly assigned 34 rats into three groups: control group
      (Group Control), MGO-induced PF rats (Group MGO) and hUCMSCs-treated rats (Group
      MGO + hUCMSCs). MiRNA microarrays and real-time PCR analyses were conducted in
      three groups. alpha-SMA, Snail1 and E-cadherin expression were detected by
      Western blot. Luciferase reporter assays were used to detect the effects of miR
      153-3p overexpression on Snai1 in rat peritoneal mesothelial cells (RPMCs). We
      identified differentially expressed miRNAs related to EMT, in which miR-153-3p
      demonstrated the greatest increase in Group MGO + hUCMSCs. Transient
      cotransfection of miR-153-3p mimics with luciferase expression plasmids resulted
      in a significant repression of Snai1 3'-untranslated region luciferase activity
      in RPMCs. These studies suggest that miR-153-3p is a critical molecule in anti
      EMT effects of hUCMSCs in MGO-induced PF rats. MiR-153-3p might exert its
      beneficial effect through directly targeting Snai1.

PMID- 29654660
TI  - Culture-specific links between maternal executive function, parenting, and
      preschool children's executive function in South Korea.
AB  - BACKGROUND: Research on the relationships between parental factors and children's
      executive function (EF) has been conducted mainly in Western cultures. AIM: This
      study provides the first empirical test, in a non-Western context, of how
      maternal EF and parenting behaviours relate to child EF. SAMPLE: South Korean
      mothers and their preschool children (N = 95 dyads) completed EF tasks. METHOD:
      Two aspects of parental scaffolding were observed during a puzzle task:
      contingency (i.e., adjusting among levels of scaffolding according to the child's
      ongoing evidence of understanding) and intrusiveness (i.e., directive, mother
      centred interactions). RESULTS AND CONCLUSIONS: Maternal EF and maternal
      contingency each accounted for unique variance in child EF, above and beyond
      child age, child language and maternal education. Maternal intrusiveness,
      however, was not significantly related to child EF. Additionally, no mediating
      role of parenting was found in the maternal and child EF link. However, child
      language was found to partially mediate the link between maternal contingency and
      child EF. These results complement prior findings by revealing distinctive
      patterns in the link between maternal EF, parenting behaviours, and child EF in
      the Korean context.

PMID- 29654661
TI  - Simulation-based education: A narrative review of the use of VERT in radiation
      therapy education.
AB  - Simulation has a long history in medical and health science training and
      education. The literature describing this history is extensive. The role
      simulation plays in many health disciplines has evolved, as has the focus of the
      literature around it. The Virtual Environment for Radiotherapy Training (VERT)
      system is a relative newcomer to radiation therapy education and, similar to the
      literature around radiation therapy (RT) education, is still in its infancy. This
      narrative review sets the scene of simulation-based education within the health
      sciences and considers the lessons learned from published work on VERT to date.
      The evidence suggests that future inquiry involving VERT should explore different
      ways in which VERT can be used to contribute to the skillset required by the
      radiation therapist of tomorrow.

PMID- 29654662
TI  - Improved dose homogeneity using electronic compensation technique for total body
      irradiation.
AB  - In total body irradiation (TBI) utilizing large parallel-opposed fields, the
      manual placement of lead compensators has conventionally been used to compensate
      for the varying thickness throughout the body. The goal of this study is to
      pursue utilizing the modern electronic compensation (E-comp) technique to more
      accurately deliver dose to TBI patients. Bilateral parallel-opposed TBI treatment
      plans were created using E-comp for 15 patients for whom CT data had been
      previously acquired. A desirable fluence pattern was manually painted within each
      field to yield a uniform dose distribution. The conventional compensation
      technique was simulated within the treatment planning system (TPS) using a field
      in-field (FIF) method. This allows for a meaningful evaluation of the E-comp
      technique in comparison to the conventional method. Dose-volume histograms (DVH)
      were computed for all treatment plans. The mean total body dose using E-comp
      deviates from the prescribed dose (4 Gy) by an average of 2.4%. The mean total
      body dose using the conventional compensation deviates from the prescribed dose
      by an average of 4.5%. In all cases, the mean body dose calculated using E-comp
      technique deviates less than 10% from that of conventional compensation. The
      average reduction in maximum dose using E-comp compared to that of the
      conventional method was 30.3% +/- 6.6% (standard deviation). In all cases, the s
      index for the E-comp technique was lower (10.5% +/- 0.7%) than that of the
      conventional method (15.8% +/- 4.4%), indicating a more homogenous dose
      distribution. In conclusion, a large reduction in maximum body dose can be seen
      using the proposed E-comp technique while still producing a mean body dose that
      accurately complies with the prescription dose. Dose homogeneity was quantified
      using s-index which demonstrated a reduction in hotspots with E-comp technique.
      Electronic compensation technique is capable of more accurately delivering a
      total body dose compared to conventional methods.

PMID- 29654663
TI  - Risk factors for breast cancer in a cohort of mammographic screening program: a
      nested case-control study within the FRiCaM study.
AB  - Breast cancer is the most common cancer diagnosis and the leading cause of cancer
      death among women in the world, and differences across populations indicate a
      role of hormonal, reproductive and lifestyle factors. This study is based on a
      cohort of 78,050 women invited to undergo a mammogram by Local Health Authority
      of Milan, between 2003 and 2007. We carried out a nested case-control study
      including all the 3303 incident breast cancer cases diagnosed up to 2015, and
      9909 controls matched by age and year of enrollment. Odds ratios (ORs) and
      corresponding 95% confidence intervals (CIs) were estimated using logistic
      regression models. The ORs were 0.88 (95% CI: 0.78-0.98) for an age at menarche
      >=14 years and 1.39 (95% CI: 1.07-1.81) for an age of 30 years or older at first
      pregnancy. Body mass index (BMI) was positively associated with breast cancer
      risk in women older than 50 years (OR = 1.89, 95% CI: 1.54-2.31, for BMI>=30 vs.
      <20), while the association tended to be inverse in younger women. A high
      mammographic density increased breast cancer risk (OR = 2.61, 95% CI: 2.02-3.38
      for density >75% vs. adipose tissue). The ORs were 1.67 (95% CI: 1.47-1.89) and
      2.04 (95% CI: 1.38-3.00) for one first-degree relative and two or more relatives
      affected by breast cancer, respectively. Our study confirms the role of major
      recognized risk factors for breast cancer in our population and provides the
      basis for a stratification of the participants in the mammographic screening
      according to different levels of risk.

PMID- 29654664
TI  - Noncontiguous finished genome sequence and description of Intestinimonas
      massiliensis sp. nov strain GD2T , the second Intestinimonas species cultured
      from the human gut.
AB  - Intestinimonas massiliensis sp. nov strain GD2T is a new species of the genus
      Intestinimonas (the second, following Intestinimonas butyriciproducens gen. nov.,
      sp. nov). First isolated from the gut microbiota of a healthy subject of French
      origin using a culturomics approach combined with taxono-genomics, it is strictly
      anaerobic, nonspore-forming, rod-shaped, with catalase- and oxidase-negative
      reactions. Its growth was observed after preincubation in an anaerobic blood
      culture enriched with sheep blood (5%) and rumen fluid (5%), incubated at 37
      degrees C. Its phenotypic and genotypic descriptions are presented in this paper
      with a full annotation of its genome sequence. This genome consists of 3,104,261
      bp in length and contains 3,074 predicted genes, including 3,012 protein-coding
      genes and 62 RNA-coding genes. Strain GD2T significantly produces butyrate and is
      frequently found among available 16S rRNA gene amplicon datasets, which leads
      consideration of Intestinimonas massiliensis as an important human gut commensal.

PMID- 29654665
TI  - Xenotransplantation literature update, January/February 2018.

PMID- 29654666
TI  - Blood parasites shape extreme major histocompatibility complex diversity in a
      migratory passerine.
AB  - Pathogens are one of the main forces driving the evolution and maintenance of the
      highly polymorphic genes of the vertebrate major histocompatibility complex
      (MHC). Although MHC proteins are crucial in pathogen recognition, it is still
      poorly understood how pathogen-mediated selection promotes and maintains MHC
      diversity, and especially so in host species with highly duplicated MHC genes.
      Sedge warblers (Acrocephalus schoenobaenus) have highly duplicated MHC genes, and
      using data from high-throughput MHC genotyping, we were able to investigate to
      what extent avian malaria parasites explain temporal MHC class I supertype
      fluctuations in a long-term study population. We investigated infection status
      and infection intensities of two different strains of Haemoproteus, that is avian
      malaria parasites that are known to have significant fitness consequences in
      sedge warblers. We found that prevalence of avian malaria in carriers of specific
      MHC class I supertypes was a significant predictor of their frequency changes
      between years. This finding suggests that avian malaria infections partly drive
      the temporal fluctuations of the MHC class I supertypes. Furthermore, we found
      that individuals with a large number of different supertypes had higher
      resistance to avian malaria, but there was no evidence for an optimal MHC class I
      diversity. Thus, the two studied malaria parasite strains appear to select for a
      high MHC class I supertype diversity. Such selection may explain the maintenance
      of the extremely high number of MHC class I gene copies in sedge warblers and
      possibly also in other passerines where avian malaria is a common disease.

PMID- 29654667
TI  - The development of Neoechinorhynchus buttnerae (Eoacanthocephala:
      Neoechinorhynchidae) in its intermediate host Cypridopsis vidua in Brazil.
AB  - The family Neoechinorhynchidae includes seven species of Neoechinorhynchus from
      freshwater fishes of Brazil. Although several Neoechinorhynchus species are cited
      infecting different fish species in Brazil, there is a lack of information
      concerning to their life cycle and the identification of the intermediate hosts.
      Thus, the aim of the present study was to describe the development of
      Neoechinorhynchus buttnerae in its intermediate host collected in a fish farm
      located in Rio Preto da Eva, Amazonas, Brazil. To verify the presence of N.
      buttnerae in the fish pond, twenty Colossoma macropomum were captured and
      analyzed, being corroborated the presence of this parasite species. Samples of
      plankton were also collected, finding the ostracod Cypridopsis vidua as the
      intermediate host. For the description of the larvae development, a laboratory
      experimental procedure was conducted by feeding the collected ostracods with the
      eggs of the adult specimens taken from the sampled fish. To observe the stages of
      development an artificial hatch was performed. Every stage of development was
      photographed, measured, drawn and described. The time of development of the
      immature stages of N. buttnerae was 29 days, reporting the stages: acanthor,
      acanthella (with eight developmental changes) and cystacanth. As high infections
      by N. buttnerae causes morphological damages to the intestine and may compromise
      the quality of C. macropomum and in consequence the production of fish farmers in
      the Brazilian Amazon region, the knowledge of its intermediate host and the
      understanding of its life cycle represents a useful information to prevent and
      combat infections by this parasite.

PMID- 29654668
TI  - Evaluation of four commercial DNA extraction kits for the detection of
      Microsporidia and the importance of pretreatments in DNA isolation.
AB  - Microsporidia are obligate intracellular parasitic protozoa infecting the wide
      variety of hosts and are commonly known as a cause of chronic diarrhea
      particularly in immunocompromised individuals. Molecular-based tests have high
      sensitivity and specificity in disease diagnosis. However, these tests'
      performance relies on the isolation of DNA in a good concentration. The standard
      procedures of commercial DNA extraction kits are usually insufficient for this
      purpose due to the tough walls of spores. This study aimed to test the
      significance of pretreatments by glass beads and freeze-thawing processes in DNA
      isolation from microsporidia spores. The parasite was cultured in growing Vero
      cells and seven serial dilutions were prepared from the collected spores. DNA
      purification was performed according to different tissue kits and stool kit
      procedures with and without any pretreatment. Concentration of isolated DNA
      samples were evaluated by real-time PCR. As a result of this study, the
      detectable amount of spores is minimum 10 spores in each 100 MU! sample according
      to the different tissue kits' standard protocols. However, according to the DNA
      stool mini kit, the detectable amount of spores was found to be 1,000 spores/100
      MUl of stool sample when pretreated with both the freeze-thawing and glass beads
      methods.In conclusion, the current study demonstrated that further pretreatments
      are an essential process for DNA extraction from the stool specimens in order to
      avoid possible false negativity in the diagnosis of microsporidiosis.

PMID- 29654669
TI  - Evaluation of frequency of antibodies against Toxoplasma gondii,Neospora caninum
      and Sarcocystis spp. and transmission routes in sheep from Humid Pampa,
      Argentina.
AB  - The aim of this study was to describe the frequency of ovine specific antibodies
      to Toxoplasma gondii, Neospora caninum and Sarcocystis spp. and to estimate
      different transmission routes of these infections. One hundred and thirty Texel
      sheep and their 117 Texel lambs were included in the study. Serum samples were
      tested for antibodies to T. gondii, N. caninum and Sarcocystis spp. using IFAT.
      Toxoplasma gondii seroprevalence was 10.00% in sheep (IC95%: 4.80-15.20%), being
      higher in adult sheep (>=12 year) than in younger sheep (OR 1.30; 95% CI, 1.10
      1.50). N. caninum and Sarcocystis spp. seroprevalences were 1.54% (IC95%: 0.00
      5.70) and 72.09% (IC95%: 67.70-82.70), respectively, with no association between
      age and seropositivity in sheep (P>0.05). T. gondii seroprevalence in lambs was
      4.27% (IC95%: 0.61-7.94). No association between T. gondii serological status in
      sheep and their lambs was detected (P = 0.07). Two T. gondii and Sarcocystis spp.
      seropositive lambs were euthanized and T. gondii and Sarcocystis spp. DNA was
      detected by PCR in their tissues. In conclusion, the increase of T. gondii
      seropositivity in relationship with sheep age and the lack of association between
      sheep-lamb serological status, suggest that horizontal infection is the main
      transmission route in this flock as reported before. Due to the low number of N.
      caninum-seropositive ewes no assumptions can be done about the impact of this
      parasite in this flock. According with previous reports, the main transmission
      route for Sarcocystis spp. in this species in the present study was horizontal.

PMID- 29654670
TI  - Isolation, identification and characterization of the nematophagous fungus
      Arthrobotrys (Monacrosporium) sinense from China.
AB  - With the development of anthelmintic resistance of parastic nematodes, it is
      necessary to isolate and study nematophagous fungi to screen out the native
      isolates for their potential in the biocontrol of domestic animal nematodosis.
      This study aimed to isolate the Arthrobotrys sinense (Monacrosporium sinense) of
      nematophagous fungus, to characterize representative molecular isolates using
      scanning electron microscope (SEM), and to determine the effect of the
      temperature and pH values on radial growth of the isolate. Five isolates were
      isolated from 1532 samples of different types, and their occurrence frequencies
      were 0.32% of the total samples. They were identified as A. sinense by means of
      morphology and the sequence of the 5.8S, 18S, and 28S rDNA, as well as internal
      transcribed spacers 1 and 2. The isolate NBS003 could grow from 11 degrees C to
      35 degrees C and had optimal growth at 30 degrees C. The isolate could grow at pH
      4 to 11, and its optimal value was obtained at pH 9. SEM results showed that 6 h
      after their addition, the second stage larvae (L2) and the third stage infective
      larvae (L3) of Haemonchus contortus were captured. L2 and L3 were penetrated by
      the fungus at 18 and 24 h post-capture, respectively. L2 and L3 were completely
      digested at 84 and 90 h post-capture, respectively. The NBS003 of the A. sinense
      should have a certain potential to be used for capturing the free-living stage of
      nematodes in sheep.

PMID- 29654671
TI  - Morphological, histological and molecular characterization of Myxobolus
      kingchowensis and Thelohanellus cf. sinensis infecting gibel carp Carassius
      auratus gibelio (Bloch, 1782).
AB  - A Myxobolus species and a Thelohanellus species infecting Carassius auratus
      gibelio (Bloch, 1782) were redescribed by their morphological, histological and
      molecular characterization. In the present study, the Myxobolus species infecting
      the muscle was identified as Myxobolus kingchowensis Chen et Ma, 1998 by the
      morphological and molecular data. Histologically, mature spores of M.
      kingchowensis were observed in the intercellular and connective tissue of muscle,
      though the plasmodia were not found. In addition, scattered spores also occurred
      in the intercellular of haematopoietic cells, intraepithelial of the renal
      tubules and interior of the melano-macrophage centres. Phylogenetic analysis
      showed that M. kingchowensis clustered in the clade of muscle-infecting Myxobolus
      species, further supporting muscle as the infection site of M. kingchowensis. The
      present Thelohanellus species infecting the gills was identified conspecific as
      Thelohanellus sinensis reported in Sun (2006) (mark it as T. sinensis-Sun)based
      on spore morphology, biological traits (host specificity and organ specificity),
      and molecular data. However, compared with the original description of T.
      sinensis Chen et Hsieh, 1960, the present Thelohanellus species and T. sinensis
      Sun both infecting the gills of gibel carp are distinguishable from the original
      description in the host and infection site, which made the validity of T.
      sinensis-Sun dubious. Due to the absence of molecular data in the original
      description of T. sinensis, we suggest marking the present species and T.
      sinensis-Sun as T. cf. sinensis to avoid the confusion until T. sinensis is
      obtained from the type host and type infection site.

PMID- 29654672
TI  - Virulent T4 Acanthamoeba causing keratitis in a patient after swimming while
      wearing contact lenses in Southern Brazil.
AB  - Several strains of free-living amoebae belonging to the genus Acanthamoeba can
      cause a painful sight-threatening disease of the cornea known as Acanthamoeba
      keratitis (AK). The numbers of AK cases keep rising worldwide mainly due to an
      increase in contact lens wearers and lack of hygiene in the maintenance of
      contact lenses and their cases. We report a case of AK in a healthy young woman
      admitted to the Hospital de Clinicas in Porto Alegre, southern Brazil. Corneal
      scrapings were examined for the presence of Acanthamoeba strains. The initial
      isolate was characterized by morphological and genotypic properties. The isolate
      belonged to group III according to Pussard and Pons' cyst morphology. Analysis of
      its 18S rDNA sequence identified the isolate as genotype T4. The T4 genotype is
      the most commonly reported among keratitis isolates and the most common in
      environmental samples.

PMID- 29654673
TI  - A new species of Chondracanthus (Cyclopoida: Chondracanthidae) parasitic on deep
      sea Dibranchus spongiosa(Lophiiformes: Ogcocephalidae) from the Eastern Central
      Pacific.
AB  - A total of 228 sampling stations were visited for benthic fauna during a series
      of oceanographic cruises in the Gulf of California, west coast of the Baja
      California Peninsula, and Eastern Central Pacific from year 1991 to 2014. Among
      others, three fish species of the genus Dibranchus were caught in 28 stations. Of
      these, D. spongiosa was the most common and abundant. Close inspection of this
      fish revealed the presence of a new species of parasitic copepod, Chondracanthus
      dibranchi sp. nov., found in the gill cavity of seven specimens of D. spongiosa.
      Chondracanthus dibranchi sp. nov. seems to be morphologically related to C.
      psetti and C. janebennettae. The female of C. janebennettae can be separated from
      these other two congeners by the general shape of the head and abdomen, by the
      number of teeth on the mandibular blade, and by the general body shape.
      Chondracanthus psetti and C. dibranchi sp. nov. share the relative lengths of
      legs 1 and 2, the relative size and shape of the genito-abdomen, and the conical
      attenuating lateral processes on the trunk of the female. The females of these
      two species can be separated by the shape and armature of the antennule, shape of
      the antenna, the claw of the maxilliped, the rami of leg 1 and 2 and posterior
      processes, the head region, and by the position of the lateral processes of the
      trunk. An amendment to Tang's (2007) key to the species of Chondracanthus is
      proposed.

PMID- 29654674
TI  - Characterization of the complete mitochondrial genome of Metastrongylus salmi (M.
      salmi) derived from Tibetan pigs in Tibet, China.
AB  - The present study was designed to determine and analyze the mt genomes of
      Metastrongylus salmi (M. salmi), and reveal the phylogenetic relationships of
      this parasite using mt DNA sequences. Results showed that the complete mt genome
      of M. salmi was 13722 bp containing 12 protein-coding genes (cox1-3, nad1-6,
      nad4L, atp6 and cytb), 22 transfer RNA genes, and 2 ribosomal RNA genes (rrnL and
      rrnS). The overall A+T content was 73.54% and the nucleotide composition was A
      (23.52%), C (6.14%), G (19.60%), T (50.02%), and N (UCAG) (0.73%). A total of
      4237 amino acids are encoded from the Tibetan isolates of M. salmi mt genomes.
      The ATA was predicted as the most common starting codon with 41.7% (5/12 protein
      genes); and 11 of the 12 protein genes were found to have a TAG or TAA
      translation termination codon. By clustering together the phylogenetic trees of
      Tibetan M. salmi and Austrian M. salmi, the M. salmi isolated from Tibetan pigs
      was found to be highly homological with that stemmed from Austrian one. This
      information provides meaningful insights into the phylogenetic position of the M.
      salmi China isolate and represents a useful resource for selecting molecular
      markers for diagnosis and population studies.

PMID- 29654675
TI  - Detection of Dirofilaria immitis antigen and antibodies against Anaplasma
      phagocytophilum, Borrelia burgdorferi and Ehrlichia canis in dogs from ten
      provinces of China.
AB  - Despite the fact vector-borne diseases (VBDs) have been increasingly reported in
      dogs worldwide, there are only limited reports on VBDs in dogs in China with most
      being based on molecular detection of active infections. To provide further data
      on the exposure of dogs in China to VBD agents, we used commercial
      immunochromatographic assays to test plasma from 637 apparently healthy indoor
      and breeding colony dogs from 21 veterinary clinics in 10 provinces in China and
      a commercial dog breeding facility for circulating antigen of Dirofilaria
      immitis, and for circulating antibodies against Ehrlichia spp., Anaplasma spp.,
      and Borrelia burgdorferi. Overall, we found only low levels of exposure to
      Ehrlichia spp. (4.7%; 30/637), Anaplasma spp. (1.4%; 9/637), B. burgdorferi
      (0.9%; 6/637) and D. immitis (0.2%; 1/637) with most of the positive animals
      coming from the commercial breeding colony (26/103; 25.2%) where ectoparasites
      were most commonly noted. At least one vector-borne agent was found in dogs from
      6 of the 10 provinces investigated. Our results confirm exposure of dogs from
      around China to a variety of VBDs, even indoor pets seldom observed to harbor
      ectoparasites.

PMID- 29654676
TI  - Histological description of Cercaria etgesii Shchenkov, 2017 daughter sporocysts
      (Trematoda: Pleurogenidae): compartmentalization of the brood cavity and germinal
      mass morphology.
AB  - Morphology of the daughter sporocysts of Cercaria etgesii Shchenkov, 2017
      (Pleurogenidae) has been described according to conventional histological
      techniques and subsequent 3D reconstruction with Bitplanelmaris(r) software.
      Novel data were obtained concerning the spatial organization of the brood cavity
      of Pleurogenidae daughter sporocysts. It was shown that the laminated structures
      of the endocyst are lining the brood cavity and carry out its
      compartmentalisation by formation of the chambers around developing and
      disintegrating embryos of cercariae. First description of the germinal mass of
      the Pleurogenidae daughter sporocysts is given. No mitoses in germinal mass were
      evident although apparent production of the cercariae embryos by the sporocysts
      take place. The analogous principle of daughter sporocysts morphofunctional
      organisation was noted for the studied representatives of closely related taxa of
      trematodes: Pleurogenidae (C. etgesii) and Microphallidae (Microphallus
      'pygmaeus' group).

PMID- 29654677
TI  - Evaluation of the protective effect of a prime-boost strategy with plasmid DNA
      followed by recombinant adenovirus expressing BmAMA1 as vaccines against Babesia
      microti infection in hamster.
AB  - In the present study, we have investigated the protective effect of a
      heterologous prime-boost strategy with priming plasmid DNA followed by
      recombinant adenovirus, both expressing BmAMA1, against Babesia microti
      infection. Four groups consisting of 3 hamsters per group were immunized with
      pBmAMA1/Ad5BmAMA1, pNull/Ad5BmAMA1, pBmAMA1/Ad5Null and pNull/Ad5Null, followed
      by challenge infection with B. microti. Our results showed that hamsters
      immunized with plasmid and adenovirus expressing BmAMA1 developed a robust IgG
      and IgG2a antibody response against BmAMA1, suggesting the DNA vaccine or viral
      vector vaccine tend to induce a Th1-biased response. Compared to the control
      hamsters, the hamsters vaccinated either with the prime-boost strategy or one of
      the two "vaccines" exhibited no significant protection against B. microti
      challenge. Although a slight difference in terms of parasitemia and hematocrit
      values at days 14-16 post challenge infection was observed, no other statistical
      difference was detected. Our results indicate that the prime-boost vaccination
      strategy of injection of plasmid and adenovirus expressing BmAMA1 is not
      efficient in protecting against B. microti infection.

PMID- 29654678
TI  - Prevalence and risk factors associated with Tritrichomonas foetus infection in
      cattle in the state of Paraiba, Brazil.
AB  - The objective of this study was to determine the prevalence of Tritrichomonas
      foetus infection and to evaluate risk factors associated with this infection
      among cattle in the state of Paraiba in northeastern Brazil. Samples of
      cervicovaginal mucus from 290 females and smegma from 59 males [beef, 31; mixed
      aptitude (beef and dairy), 10; and dairy, 18] from 31 farms were collected.
      Modified Diamond's medium and polymerase chain reaction (PCR) were used for the
      laboratory diagnosis of T. foetus infection. Univariate analysis and logistic
      regression were performed to test for potential risk factors in addition to
      prevalence mapping. No sample was positive for T. foetus in culture, and the
      prevalence of T. foetus infection using PCR was 3.7% (13/349) [confidence
      interval (CI) 95%, 2.1%-6.4%]. In total, 19.3% (6/31) of the farms had at least
      one animal positive for T. foetus. The contact of females with males from other
      farms [Odds ratio, 5.9; 95% CI, 1.5-22.4; p = 0.009] was identified as a risk
      factor for T. foetus infection. This study demonstrates that T. foetus infection
      is prevalent among dairy cows in the state of Paraiba, Brazil. Sexual resting,
      removal of positive females, and avoiding contact of females with males from
      other farms are recommended to reduce the risk of infection.

PMID- 29654679
TI  - Structural predication and antigenic analysis of Toxoplasma gondii ROP20.
AB  - Toxoplasma gondii infects almost all the warm-blooded animals. ROP20 protein is
      expressed in the rhoptry of Toxoplasma gondii. In this study, the secondary
      structure of ROP20 was analyzed using SMART software. We constructed and analyzed
      the 3D model of ROP20 protein using SWISS-MODEL online procedure and Visual
      Molecular Dynamics (VMD) software. The structure analysis fully indicated that
      ROP20 protein is an important member of the ROP family. Furthermore, We used
      DNASTAR software and Epitope Database online service to analyze liner-B cell
      epitopes and T-cell epitopes of ROP20 protein. All the analysis results of ROP20
      protein can provide positive information on treatment and vaccine for
      toxoplasmosis. Moreover, ROP20 gene was obtained from PCR, and a recombinant
      eukaryotic expression vector (pEGFP-C1-ROP20) was constructed in the following
      study. After restriction enzyme digestion, the constructed plasmid was
      transfected into HEK 293-T cells. The RT-PCR result indicated that the
      recombinant plasmid could transcribe successfully in HEK 293-T cell. The results
      of western blotting indicated the expressed proteins can be recognized by anti
      STAg mouse sera.

PMID- 29654680
TI  - Primary culture of cat intestinal epithelial cells in vitro and the cDNA library
      construction.
AB  - Felids are the only definitive hosts of Toxoplasma gondii. To lay a foundation
      for screening the T. gondii-felids interaction factors, we have developed a
      reproducible primary culture method for cat intestinal epithelial cells (IECs).
      The primary IECs were isolated from a new born cat's small intestine jejunum
      region without food ingress, and respectively in vitro cultured by tissue
      cultivation and combined digestion method with collagenase XI and dispase I, then
      purified by trypsinization. After identification, the ds cDNA of cat IECs was
      synthesized for constructing pGADT7 homogenization three-frame plasmid, and
      transformed into the yeast Y187 for generating the cDNA library. Our results
      indicated that cultivation of primary cat IECs relays on combined digestion to
      form polarized and confluent monolayers within 3 days with typical features of
      normal epithelial cells. The purified cells cultured by digestion method were
      identified to be nature intestinal epithelial cells using immunohistochemical
      analysis and were able to maintain viability for at least 15 passages. The
      homogenizable ds cDNA, which is synthesized from the total RNA extracted from our
      cultured IECs, distributed among 0.5-2.0 kb, and generated satisfying three-frame
      cDNA library with the capacity of 1.2 * 106 and the titer of 5.2 * 107 pfu/mL.
      Our results established an optimal method for the culturing and passage of cat
      IECs model in vitro, and laid a cDNA library foundation for the subsequent
      interaction factors screening by yeast two-hybrid.

PMID- 29654681
TI  - Presence of Acanthamoeba in the ocular surface in a Spanish population of contact
      lens wearers.
AB  - Pathogenic strains of Acanthamoeba are causative agents of a sight-threatening
      infection of the cornea known as Acanthamoeba keratitis (AK) which mainly affects
      contact lens wearers and it is commonly related to poor hygiene of contact lenses
      and their cases. Moreover, treatment of AK is complex due to the existence of a
      highly resistant cyst stage and if not diagnosed early has poor prognosis,
      leading to blindness and/or keratoplasty. Even though AK is increasing worldwide
      as well as awareness among patients and clinicians, it is still a poorly studied
      pathogen. Additionally, a remaining question to be answered is whether these
      opportunistic pathogens are present in the ocular surface of healthy contact lens
      wearers since they are the main group at risk.In order to carry out this study,
      sterile Schirmer strip tests were collected from a group of individuals all of
      them contact lens wearers who were attending a local ophthalmology clinic in
      Tenerife, Canary Islands, Spain. The collected samples (100 eyes of 50 patients)
      were cultured in 2% Non-Nutrient Agar (NNA) plates and positive plates (16) were
      then cultured in axenic conditions for further analyses. Molecular analysis
      classified all isolated strains belonged to Acanthamoeba genotype T4 and
      osmotolerance and thermotolerance assays revealed that all strains were
      potentially pathogenic. In conclusion, the ocular surface of contact lens wearers
      included in this study was colonized by potentially pathogenic strains of
      Acanthamoeba and should be considered as a risk for AK infection in this region
      and worldwide.

PMID- 29654682
TI  - Genetic diversity of Taenia hydatigena in the northern part of the West Bank,
      Palestine as determined by mitochondrial DNA sequences.
AB  - Cysticercus tenuicollis is the metacestode of canine tapeworm Taenia hydatigena,
      which has been reported in domestic and wild ruminants and is causing veterinary
      and economic losses in the meat industry. This study was conducted to determine
      the sequence variation in the mitochondrial cytochrome c oxidase subunit 1 (coxl)
      gene in 20 isolates of T. hydatigena metacestodes (cysticercus tenuicollis)
      collected from northern West Bank in Palestine. Nine haplotypes were detected,
      with one prevailing (55%). The total haplotype diversity (0.705) and the total
      nucleotide diversity (0.0045) displayed low genetic diversity among our isolates.
      Haplotype analysis showed a star-shaped network with a centrally positioned
      common haplotype. The Tajima's D, and Fu and Li's statistics in cysticercus
      tenuicollis population of this region showed a negative value, indicating
      deviations from neutrality and both suggested recent population expansion for the
      population. The findings of this study would greatly help to implement control
      and preventive measures for T. hydatigena larvae infection in Palestine.

PMID- 29654683
TI  - First report of Cryptosporidium parvum in a dromedary camel calf from Western
      Australia.
AB  - Cryptosporidium is an important enteric parasite that can contribute large
      numbers of infectious oocysts to drinking water catchments. As a result of its
      resistance to disinfectants including chlorine, it has been responsible for
      numerous waterborne outbreaks of gastroenteritis. Wildlife and livestock play an
      important role in the transmission of Cryptosporidium in the environment. Studies
      conducted outside Australia have indicated that camels may also play a role in
      the transmission of zoonotic species of Cryptosporidium. Despite Australia being
      home to the world's largest camel herd, nothing is known about the prevalence and
      species of Cryptosporidium infecting camels in this country. In the present
      study, C. parvum was identified by PCR amplification and sequencing of a formalin
      fixed intestinal tissue specimen from a one-week old dromedary camel (Camelus
      dromedarius). Subtyping analysis at the glycoprotein 60 (gp60) locus identified
      C. parvum subtype IIaA17G2R1, which is a common zoonotic subtype reported in
      humans and animals worldwide. Histopathological findings also confirmed the
      presence of large numbers of variably-sized (1-3 um in diameter) circular
      basophilic protozoa - consistent with Cryptosporidium spp.- adherent to the
      mucosal surface and occasionally free within the lumen. Further analysis of the
      prevalence and species of Cryptosporidium in camel populations across Australia
      are essential to better understand their potential for contamination of drinking
      water catchments.

PMID- 29654684
TI  - First molecular characterization and morphological aspects of Sarcocystis
      fusiformis infecting water buffalo Bubalus bubalis in Egypt.
AB  - Fresh muscle samples from water buffalo (Bubalus bubalis) aged 2-15, from Giza
      Province, Egypt; were examined for Sarcocystis infection. Macroscopic ovoid
      sarcocysts embedded in the muscle tissues of the examined buffaloes were
      detected; they measured 152-230 (210 +/- 7) MUm in length and 37-119 (95 +/- 3)
      MUm in width. The esophagus was the most infected organ followed by the
      diaphragm, and tongue, while the heart muscles were the least infected. The cyst
      cavity was compartmentalized by septa derived from the ground substance located
      under the primary cyst wall. Using transmission electron microscopy, the primary
      cyst wall bordered sarcocysts were determined to be 0.08-0.22 MUm in thickness,
      raised from the parasitophorous vacuolar membrane, and surrounded by a secondary
      cyst wall of host origin. The primary cyst wall had irregular wall folds with
      numerous cauliflower-like projections of variable sizes and shapes accompanied by
      knob-like electron-dense elevations. 18S rRNA gene expression studies confirmed
      that the present parasite isolates belonged to the genus Sarcocystis. The
      sequence data showed significant identities (>90%) with archived gene sequences
      from many Eimeriidae organisms, and a dendogram showing the phylogenetic
      relationship was constructed. The most closely related species was Sarcocystis
      fusiformis KR186117, with an identity percentage of 98%. The recovered sequences
      were deposited in the GenBank under the accession number MG572125. The present
      study, to our knowledge, is the first collective ultrastructural and molecular
      study that confirmed the taxonomy of sarcocysts isolated from water buffaloes in
      Egypt as Sarcocystis fusiformis.

PMID- 29654685
TI  - Cystic echinococcosis in animals and humans of Maharashtra State, India.
AB  - Echinococcosis/hydatidosis which is a neglected parasitic zoonosis in the
      developing country like India. The study was conducted during April, 2010 to
      March, 2017 to determine the prevalence among slaughtered food animals, dogs and
      human. The samples were collected from the various slaughterhouses situated in
      different regions of Maharashtra state. A total of 9464 cattle (male), 3661
      buffalo, 47189 sheep, 33350 goats and 13579 pigs were scientifically examined
      during PM inspection at different slaughterhouses. The study revealed that the
      prevalence of disease in cattle (3.00%) was highest followed by buffalo (2.05%),
      pig (1.28%), sheep (0.09%) and goat (0.01%), by PM examination. The average
      estimated economic losses (direct and indirect) due to hydatidosis were Rs.
      8,65,83,566 in cattle, Rs. 44,33,93,900 in buffalo, Rs. 7,24,50,615 in sheep, Rs.
      1,88,29,359 in goat and Rs. 5,20,49,081 in pigs. Dog faecal samples analyzed and
      showed the prevalence of echinococcosis as 4.34% (19/438) by sedimentation method
      and positive samples were confirmed by PCR assay, whereas in high risk human,
      11.09% sera samples were found to be positive for echinococcosis. However, based
      on data collection for seven years, 58 patients were found to be surgically
      operated for hydatid cyst removal. The results of the present study indicated
      that cystic echinococcosis/hydatidosis is prevalent in both human and animal
      population in study areas which attracts serious attention from veterinary and
      public health authority to reduce economic burden and in designing appropriate
      strategy for prevention and control of disease.

PMID- 29654686
TI  - Balantioides coli: morphological and ultrastructural characteristics of pig and
      non-human primate isolates.
AB  - Balantioides coli is a ciliated protozoon that inhabits the intestine of pigs,
      non-human primates and humans. Light microscopy studies have described over 50
      species of the genus Balantioides but their validity is in doubt. Due to the
      limited information about this genus, this study is aimed to identify
      morphological characteristics of Balantioides coli isolated using fluorescence
      microscopy and both scanning (SEM) and transmission electron microscopy (TEM).
      Trophozoites isolated from the feces of pig and macaque were washed and subjected
      to centrifugation. These cells were fixed with paraformaldehyde for
      immunofluorescence. Other aliquots of these trophozoites were fixed with
      glutaraldehyde, post fixed with osmium tetroxide and processed for SEM and TEM.
      Immunofluorescence studies revealed microtubules with a longitudinal distribution
      to the main axis of the parasite and in the constitution of cilia. SEM
      demonstrated a high concentration of cilia covering the oral apparatus and a poor
      presence of such structures in cytopyge. TEM revealed in the plasma membrane,
      several associated structures were observed to delineate the cellular cortex and
      mucocysts. The cytoskeleton of the oral region was observed in detail and had an
      organization pattern consisting of microtubules, which formed files and
      nematodesmal networks. Organelles such as hydrogenosomes like and peroxisomes
      were observed close to the cortex. Macronuclei were observed, but structures that
      were consistent with micronuclei were not identified. Ultrastructural
      morphological analysis of isolates confirms its similarity to Balantioides coli.
      In this study were identified structures that had not yet been described, such as
      hydrogenosomes like and cytoskeletal structures.

PMID- 29654687
TI  - Molecular cloning of enolase from Trichinella spiralis and the protective
      immunity in mice.
AB  - Trichinella spiralis, the main pathogen of trichinosis, infects a wide range of
      mammalian hosts and is one of the most widespread parasites worldwide. For
      parasites, glycolysis is the most important way to generate energy. Previous
      studies showed that some enzymes involved in the glycolytic pathway play roles in
      regulation the host immunity. In this paper, enolase from T. spiralis was cloned
      and the protective potentials were studied. One hundred and sixty ICR mice were
      divided into four groups and vaccinated with recombinant enolase (pET-ENO),
      eukaryotic recombinant plasmid encoding enolase (pVAX1-ENO) and negative controls
      (pVAXl and PBS), respectively. Two weeks after the second immunization, each
      mouse was challenged orally with 200 muscle larvae (MLs) of T. spiralis. Results
      showed that mice vaccinated with pET-ENO and pVAX1-ENO induced specific
      antibodies of IgG, IgA, IgM, but no IgE. Subclasses of IgG antibodies showed that
      mice immunized with recombinant protein and recombinant plasmids induced a
      Th1/Th2 immune response. Concentrations of serum cytokines were detected and
      showed significant increase of IFN-gamma, IL-4 and TGFbeta1, while IL-17 in each
      group was not significantly different. Flow cytometric analysis showed
      significant increase of CD4+ and CD8+ T lymphocytes in the groups immunized with
      recombinant protein and recombinant plasmids. Challenge infection demonstrated
      that immunized groups had a reduced number of worm burdens. The reductions of
      larvae per gram muscle (LPG) in pET-ENO and pVAX1-ENO group were 17.7% and 15.8%
      when compared with PBS control.

PMID- 29654688
TI  - Entamoeba histolytica L220 induces the in vitro activation of macrophages and
      neutrophils and is modulated by neurotransmitters.
AB  - The neuroimmunoregulation of inflammation has been well characterized. Entamoeba
      histolytica provokes an inflammatory response in the host in which macrophages
      and neutrophils are the first line of defense. The aim of this study was to
      analyze the effect of the 220 kDa lectin of Entamoeba histolytica on stimulation
      of human macrophages and neutrophils, especially the secretion of cytokines and
      the relation of these to neurotransmitters. Human cells were interacted with
      L220, epinephrine, nicotine, esmolol and vecuronium bromide. The concentrations
      of IL-1beta, IFN-gamma, TNF-alpha and IL-10 were determined by ELISA at, 4 h of
      interaction. L220 has a cytokine stimulating function of macrophages and
      neutrophils for secretion of IL-1beta, and IL-10 only by macrophages, which was
      modulated by the effect of vecuronium on cholinergic receptors in this immune
      cells.

PMID- 29654689
TI  - Genotyping and virulence analysis of Toxoplasma gondii isolates from a dead human
      fetus and dead pigs in Jiangsu province, Eastern China.
AB  - Toxoplasma gondii is an obligate intracellular parasite with worldwide
      distribution. Virulence of T. gondii is a multigenic trait. Genetic and virulence
      data for T. gondii isolates from humans and animals in China have been reported.
      However, almost all biological materials used for genotyping of T. gondii from
      humans and pigs were DNA samples prepared from tissues, and T. gondii strains
      used for virulence analysis were isolated mainly from cats. In this study, one
      isolate from a dead human fetus was identified as type I (ToxoDB #10) while the
      two isolates from dead pigs were type Chinese I (ToxoDB #9) with PCR-restriction
      fragment length polymorphism using 10 markers (SAG1, SAG2, SAG3, BTUB, GRA6, c22
      8, c29-2, L358, PK1 and Apico). Three isolates were comfirmed as virulent strains
      in mice. By cloning and sequences analysis, all isolates contained a Pvu II
      restriction site (572-577 bp) in the KHB fragment and five tandem repeats in the
      5' UTR region of SAG1, which were associated with T. gondii virulence. The type
      Chinese I isolates contained two deletions of 15 and 3 bp at positions 635 to 649
      and 658 to 660 in the GRA6, which were correlated with genotype, but not with
      virulence. To our knowledge, this is the first report on the systematic analysis
      of murine virulence of type Chinese I strain from pigs, and the associations of
      sequences of the KHB fragment and SAG1 with virulence of type Chinese I strain.
      The Chinese I genotype was more closely related to type II strains.

PMID- 29654690
TI  - Patterns of the parasite communities in a fish assemblage of a river in the
      Brazilian Amazon region.
AB  - This paper characterizes the pattern of ectoparasite and endoparasite communities
      in an assemblage of 35 sympatric fish from different trophic levels in a
      tributary from the Amazon River system, northern Brazil. In detritivorous,
      carnivorous, omnivorous and piscivorous hosts, the species richness consisted of
      82 ectoparasites and endoparasites, but protozoan ectoparasites such as
      Ichthyophthirius multifiliis, Piscinoodinium pillulare and Tripartiella sp. were
      dominant species predominated, such that they were present in 80% of the hosts.
      The taxon richness was in the following order: Monogenea > Nematoda > Digenea >
      Crustacea > Protozoa > Acanthocephala = Cestoda > Hirudinea. Among the hosts, the
      highest number of parasitic associations occurred in Satanoperca jurupari,
      Aequidens tetramerus, Hoplerythrinus unitaeniatus, Hoplosternum littorale,
      Cichlasoma amazonarum, Chaetobranchus flavescens, Squaliforma emarginata,
      Chaetobranchopsis orbicularis and Hoplias malabaricus. A weak positive
      correlation between ectoparasite abundance and length of the hosts was observed.
      Ectoparasite communities of detritivorous, carnivorous and omnivorous hosts were
      similar, but these differed from the communities of piscivorous hosts. Larval
      endoparasite species with low host specificity were the main determinants of the
      parasite infracommunity structure of the fish assemblage. Fish assemblage had few
      species of helminth that were specialist endoparasites, while many were parasites
      at the larval stage, infecting intermediate and paratenic hosts. Finally,
      carnivorous and omnivorous hosts harbored endoparasite communities that were more
      heterogeneous than those of detritivorous and piscivorous hosts. This result
      lends supports to the notion that the feeding habits of the host species are a
      significant factor in determining the endoparasites fauna.

PMID- 29654691
TI  - A new species of Cacatuocotyle (Monogenea, Dactylogyridae) parasitizing Astyanax
      spp. (Characiformes, Characidae) from Brazil, including molecular data and a key
      to species identification.
AB  - The present study describes Cacatuocotyle papilionis n. sp. (Monogenea,
      Dactylogyridae) from the skin of the characid fishes Astyanax lacustris (Lutken,
      1875) (=Astyanax altiparanae Garutti & Britski, 2000) and Astyanax fasciatus
      (Cuvier, 1819) (Characiformes, Characidae) from the Southeast of Brazil,
      supported by morphological and molecular data. The new species differs from all
      congeners, mainly due to the morphology of the ventral bar (resembling a
      butterfly), accessory piece, and the number of rings of the male copulatory organ
      (MCO), comprising a coiled tube with 4.5-5.5 counterclockwise rings. The first
      molecular data for this monogenean genus is provided in this study, using the
      partial sequences of the ribosomal gene (28S), as well as providing an
      identification key to the species.

PMID- 29654693
TI  - Assessment of genetic diversity in ragi [Eleusine coracana (L.) Gaertn] using
      morphological, RAPD and SSR markers.
AB  - Finger millet (Eleusine coracana L. Gaertn., 2n=36) is one of the most important
      minor crops, commonly known as 'ragi' and used as a staple food grain in more
      than 25 countries including Africa and south Asia. Twenty-seven accessions of
      ragi were collected from different parts of India and were evaluated for morpho
      genetic diversity studies. Simple sequence repeat (SSR) and random amplified
      polymorphic DNA (RAPD) markers were used for assessment of genetic diversity
      among 27 genotypes of E. coracana. High degree of similarity (90%) was obtained
      between 'IC49979A' and 'IC49974B' genotypes, whereas low level of similarity
      (9.09%) was found between 'IC204141' and 'IC49985' as evident in morphological
      and DNA markers. A total of 64 SSR and 301 RAPD amplicons were produced, out of
      which 87.50% and 77.20% DNA fragments showed polymorphism, respectively. The
      clustering pattern obtained among the genotypes corresponded well with their
      morphological and cytological data with a monophyletic origin of this species
      which was further supported by high bootstrap values and principal component
      analysis. Cluster analysis showed that ragi accessions were categorised into
      three distinct groups. Genotypes IC344761, IC340116, IC340127, IC49965 and
      IC49985 found accession specific in RAPD and SSR markers. The variation among
      ragi accessions might be used as potential source of germplasm for crop
      improvement.

PMID- 29654692
TI  - Adult height in patients with familial male-limited precocious puberty and the
      role of an aromatase inhibitor in patient management.
AB  - BACKGROUND: There is little adult height data in patients with familial male
      limited precocious puberty (FMPP) and no management consensus. We assessed the
      treatment and adult height in local patients with FMPP and those reported in the
      literature. METHODS: Growth data were obtained on four local patients with FMPP
      and a search performed to obtain management details and adult height data on
      cases in the literature. UK (90) population standards were used to calculate
      standard deviation scores (SDS). RESULTS: Adult height data were available on 25
      men with FMPP of whom 21 were treated. Median adult height SDS of patients was 
      1.5 SD with a mid-parental target of -0.6 SD (p=0.1). Eight patients (32%) had an
      adult height above the mid-parental target and seven patients (28%) had a height
      >2 SD below the mean. The median height SD was -0.03 in untreated patients and
      +0.5 SD in those receiving an aromatase inhibitor. There was no relationship
      between height and age at presentation. CONCLUSIONS: Aromatase inhibitor therapy
      is associated with a positive height outcome in FMPP but the outcome with and
      without intervention is unpredictable. Clinicians need to be cautious when
      counselling families about the potential height outcome in FMPP.

PMID- 29654694
TI  - High Expression of Retinoic Acid Induced 14 (RAI14) in Gastric Cancer and Its
      Prognostic Value.
AB  - BACKGROUND To explore the expression level of retinoic acid induced 14 (RAI14) in
      gastric cancer (GC) patients and its potentially clinical prognostic value.
      MATERIAL AND METHODS Initially, The Cancer Genome Atlas (TCGA) and Oncomine
      databases were mined to examine the differential expression levels and clinical
      prognostic significance of RAI14 mRNA in GC patients. Subsequently, 68 cases of
      GC and paired adjacent normal tissues were collected retrospectively, and the
      expression level of RAI14 protein was detected by immunohistochemical staining.
      In addition, Kaplan-Meier univariate and Cox multivariate survival analyses were
      used to verify the correlation between RAI14 expression and clinicopathological
      parameters in GC patients and its clinical prognostic significance. RESULTS TCGA
      and GEO (from Oncomine database) data mining results found that RAI14 mRNA level
      was remarkably higher in GC than normal gastric tissues (All P<0.05). Besides,
      immunohistochemical results detected that RAI14 protein level in GC was
      dramatically higher (P=0.004) compared to that in the matched normal tissues.
      Moreover, TCGA database and Kaplan-Meier Plotter mining results showed that
      compared to those with RAI14 low mRNA expression levels, GC patients with RAI14
      high mRNA expression levels had remarkably lower time of both overall survival
      and disease-free survival (All P<0.05). Additionally, based on the
      immunohistochemical results, Kaplan-Meier univariate and Cox multivariate
      survival analyses indicated that high expression of RAI14 was the only
      independent predictor of unfavorable prognosis in patients with gastric cancer
      (P=0.000). CONCLUSIONS RAI14 was highly expressed in GC, and the high expression
      of RAI14 could be an independent predictor of poor prognosis in GC patients.

PMID- 29654695
TI  - Is depression screening in patients with acne critical?

PMID- 29654696
TI  - A core domain set for hidradenitis suppurativa trial outcomes: an international
      Delphi process.
AB  - BACKGROUND: There is no consensus on core outcome domains for hidradenitis
      suppurativa (HS). Heterogeneous outcome measure instruments in clinical trials
      likely leads to outcome-reporting bias and limits the ability to synthesize
      evidence. OBJECTIVES: To achieve global multistakeholder consensus on a core
      outcome set (COS) of domains regarding what to measure in clinical trials for HS.
      METHODS: Six stakeholder groups participated in a Delphi process that included
      five anonymous e-Delphi rounds and four face-to-face consensus meetings to reach
      consensus on the final COS. The aim was for a 1 : 1 ratio of patients to
      healthcare professionals (HCPs). RESULTS: A total of 41 patients and 52 HCPs from
      19 countries in four continents participated in the consensus process, which
      yielded a final COS that included five domains: pain, physical signs, HS-specific
      quality of life, global assessment and progression of course. A sixth domain,
      symptoms, was highly supported by patients and not by HCPs but is recommended for
      the core domain set. CONCLUSIONS: Routine adoption of the COS in future HS trials
      should ensure that core outcomes of importance to both patients and HCPs are
      collected.

PMID- 29654697
TI  - Melatonin disturbs SUMOylation-mediated crosstalk between c-Myc and nestin via
      MT1 activation and promotes the sensitivity of paclitaxel in brain cancer stem
      cells.
AB  - Here the underlying antitumor mechanism of melatonin and its potency as a
      sensitizer of paclitaxel was investigated in X02 cancer stem cells. Melatonin
      suppressed sphere formation and induced G2/M arrest in X02 cells expressing
      nestin, CD133, CXCR4, and SOX-2 as biomarkers of stemness. Furthermore, melatonin
      reduced the expression of CDK2, CDK4, cyclin D1, cyclin E, and c-Myc and
      upregulated cyclin B1 in X02 cells. Notably, genes of c-Myc related mRNAs were
      differentially expressed in melatonin-treated X02 cells by microarray analysis.
      Consistently, melatonin reduced the expression of c-Myc at mRNA and protein
      levels, which was blocked by MG132. Of note, overexpression of c-Myc increased
      the expression of nestin, while overexpression of nestin enhanced c-Myc through
      crosstalk despite different locations, nucleus, and cytoplasm. Interestingly,
      melatonin attenuated small ubiquitin-related modifier-1 (SUMO-1) more than SUMO-2
      or SUMO-3 and disturbed nuclear translocation of nestin for direct binding to c
      Myc by SUMOylation of SUMO-1 protein by immunofluorescence and
      immunoprecipitation. Also, melatonin reduced trimethylated histone H3K4me3 and
      H3K36me3 more than dimethylation in X02 cells by Western blotting and chromatin
      immunoprecipitation assay. Notably, melatonin upregulated MT1, not MT2, in X02
      cells and melatonin receptor inhibitor luzindole blocked the ability of melatonin
      to decrease the expression of nestin, p-c-Myc(S62), and c-Myc. Furthermore,
      melatonin promoted cytotoxicity, sub-G1 accumulation, and apoptotic body
      formation by Paclitaxcel in X02 cells. Taken together, these findings suggest
      that melatonin inhibits stemness via suppression of c-Myc, nestin, and histone
      methylation via MT1 activation and promotes anticancer effect of Paclitaxcel in
      brain cancer stem cells.

PMID- 29654698
TI  - SunSmart schools: a New Zealand skin cancer primary prevention intervention
      blueprint for primary school settings.

PMID- 29654699
TI  - A smartphone application supporting patients with psoriasis improves adherence to
      topical treatment: a randomized controlled trial.
AB  - BACKGROUND: Adherence to topical psoriasis treatments is low, which leads to
      unsatisfactory treatment results. Smartphone applications (apps) for patient
      support exist but their potential to improve adherence has not been
      systematically evaluated. OBJECTIVES: To evaluate whether a study-specific app
      improves adherence and reduces psoriasis symptoms compared with standard
      treatment. METHODS: We conducted a randomized controlled trial (RCT,
      clinicaltrials.gov registration: NCT02858713). Patients received once-daily
      medication [calcipotriol/betamethasone dipropionate (Cal/BD) cutaneous foam] and
      were randomized to no app (n = 66) or app intervention (n = 68) groups. In total,
      122 patients (91%) completed the 22-week follow-up. The primary outcome was
      adherence, which was defined as medication applied >= 80% of days during the
      treatment period and assessed by a chip integrated into the medication dispenser.
      Secondary outcomes were psoriasis severity measured by the Lattice System
      Physician's Global Assessment (LS-PGA) and quality of life, measured using the
      Dermatology Life Quality Index (DLQI) at all visits. RESULTS: Intention-to-treat
      analyses using regression was performed. More patients in the intervention group
      were adherent to Cal/BD cutaneous foam than those in the nonintervention group at
      week 4 (65% vs. 38%, P = 0.004). The intervention group showed a greater LS-PGA
      reduction than the nonintervention group at week 4 (mean 1.86 vs. 1.46, P =
      0.047). A similar effect was seen at weeks 8 and 26, although it did not reach
      statistical significance. CONCLUSIONS: This RCT demonstrates that the app
      improved short-term adherence to Cal/BD cutaneous foam treatment and psoriasis
      severity.

PMID- 29654701
TI  - Vedolizumab-induced acne in inflammatory bowel disease.

PMID- 29654703
TI  - Asymmetric oceanographic processes mediate connectivity and population genetic
      structure, as revealed by RADseq, in a highly dispersive marine invertebrate
      (Parastichopus californicus).
AB  - Marine populations are typically characterized by weak genetic differentiation
      due to the potential for long-distance dispersal favouring high levels of gene
      flow. However, strong directional advection of water masses or retentive
      hydrodynamic forces can influence the degree of genetic exchange among marine
      populations. To determine the oceanographic drivers of genetic structure in a
      highly dispersive marine invertebrate, the giant California sea cucumber
      (Parastichopus californicus), we first tested for the presence of genetic
      discontinuities along the coast of North America in the northeastern Pacific
      Ocean. Then, we tested two hypotheses regarding spatial processes influencing
      population structure: (i) isolation by distance (IBD: genetic structure is
      explained by geographic distance) and (ii) isolation by resistance (IBR: genetic
      structure is driven by ocean circulation). Using RADseq, we genotyped 717
      individuals from 24 sampling locations across 2,719 neutral SNPs to assess the
      degree of population differentiation and integrated estimates of genetic
      variation with inferred connectivity probabilities from a biophysical model of
      larval dispersal mediated by ocean currents. We identified two clusters
      separating north and south regions, as well as significant, albeit weak,
      substructure within regions (FST  = 0.002, p = .001). After modelling the
      asymmetric nature of ocean currents, we demonstrated that local oceanography
      (IBR) was a better predictor of genetic variation (R2  = .49) than geographic
      distance (IBD) (R2  = .18), and directional processes played an important role in
      shaping fine-scale structure. Our study contributes to the growing body of
      literature identifying significant population structure in marine systems and has
      important implications for the spatial management of P. californicus and other
      exploited marine species.

PMID- 29654700
TI  - FACE-Q Skin Cancer Module for measuring patient-reported outcomes following
      facial skin cancer surgery.
AB  - BACKGROUND: The patient's perspective of their facial scar after skin cancer
      surgery influences perception of care and quality of life (QoL). Appearance
      satisfaction after surgery is also an important but often overlooked treatment
      outcome. OBJECTIVES: To report the psychometric validation of the FACE-Q Skin
      Cancer Module consisting of five scales, measuring appearance satisfaction
      (Satisfaction with Facial Appearance, Appraisal of Scars), QoL (Cancer Worry,
      Appearance-related Psychosocial Distress) and the patient experience
      (Satisfaction with Information: Appearance). METHODS: Participants underwent Mohs
      surgery for facial basal or squamous cell carcinoma or excision of early facial
      melanoma. Cohort 1 received a set of scales before and after surgery. Cohort 2
      received the scales on two occasions in the postoperative period for test-retest
      reliability. Rasch measurement theory was used to select (item-reduce) the most
      clinically meaningful items for the scales. Reliability, validity, floor and
      ceiling effects and responsiveness were also analysed. RESULTS: Of 334 patients,
      209 (response rate 62.6%) were included. Rasch analysis reduced the total scale
      items from 77 to 41. All items had ordered thresholds and good psychometric fit.
      Reliability was high (Person separation index and Cronbach's alpha >= 0.90) and
      scales measuring similar constructs were correlated. High floor and ceiling
      effects were seen for the scales. The Cancer Worry scale demonstrated
      responsiveness (P = 0.004). CONCLUSIONS: The FACE-Q Skin Cancer Module meet the
      requirements of the Rasch model providing linearized measurement. Discriminating
      between patients with minimal appearance or worry impairment may be a limitation.
      The scales can be used for larger validation studies, clinical practice and
      research.

PMID- 29654704
TI  - Is depression screening in patients with acne critical?: reply from authors.

PMID- 29654706
TI  - Arteriovenous specification: BMPER and TWSG1 determine endothelial cell fate via
      activation of synergistic BMP and Notch signaling.
AB  - Two extracellular BMP modulators, BMPER and TWSG1, act in a pro-BMP fashion to
      activate endothelial-specific members of the TGF-beta/BMP receptor family.
      Through cross-talk with the Notch signaling pathways, they are key regulators of
      downstream Notch targets, including ephrin B2. This adds to our understanding of
      BMP and Notch signaling, how these pathways converge, and thereby control
      arteriovenous specification.

PMID- 29654707
TI  - Melatonin promotes sleep in mice by inhibiting orexin neurons in the perifornical
      lateral hypothalamus.
AB  - Melatonin promotes sleep. However, the underlying mechanisms are unknown. Orexin
      neurons in the perifornical lateral hypothalamus (PFH) are pivotal for wake
      promotion. Does melatonin promote sleep by inhibiting orexin neurons? We used
      C57BL/6J mice and designed 4 experiments to address this question. Experiment 1
      used double-labeled immunofluorescence and examined the presence of melatonin
      receptors on orexin neurons. Second, mice, implanted with bilateral guides
      targeted toward PFH and sleep-recording electrodes, were infused with melatonin
      (500 pmole/50 nL/side) at dark onset (onset of active period), and spontaneous
      bouts of sleep-wakefulness were examined. Third, mice, implanted with bilateral
      guides into the PFH, were infused with melatonin (500 pmole/50 nL/side) at dark
      onset and euthanized 2 hours later, to examine the activation of orexin neurons
      using c-Fos expression in orexin neurons. Fourth, mice, implanted with PFH
      bilateral guides and sleep-recording electrodes, were infused with melatonin
      receptor antagonist, luzindole (10 pmol/50 nL/side), at light onset (onset of
      sleep period), and spontaneous bouts of sleep-wakefulness were examined. Our
      results suggest that orexin neurons express MT1, but not MT2 receptors. Melatonin
      infusion into the PFH, at dark onset, site-specifically and significantly
      increased NREM sleep (43.7%, P = .003) and reduced wakefulness (12.3%, P = .013).
      Local melatonin infusion at dark onset inhibited orexin neurons as evident by a
      significant reduction (66%, P = .0004) in the number of orexin neurons expressing
      c-Fos. Finally, luzindole infusion-induced blockade of melatonin receptors in PFH
      at sleep onset significantly increased wakefulness (44.1%, P = .015). Based on
      these results, we suggest that melatonin may act via the MT1 receptors to inhibit
      orexin neurons and promote sleep.

PMID- 29654708
TI  - Hyponatremia in neuromyelitis optica spectrum disorders: Literature review.
AB  - Hyponatremia is a potentially serious electrolyte abnormality observed in
      neuromyelitis optica spectrum disorders (NMOSDs), and its most common cause is
      syndrome of inappropriate antidiuretic hormone secretion (SIADH). Another
      potential cause of hyponatremia is cerebral salt-wasting syndrome (CSWS),
      although CSWS has not previously been reported in NMOSDs. Accurate and early
      differentiation between SIADH and CSWS is difficult. However, the two conditions
      have important implications for the selection of therapy. Here, we describe two
      patients with aquaporin-4 antibody (AQP4-Ab)-positive NMOSDs who developed
      hyponatremia as a result of CSWS and SIADH, respectively. Additionally, we review
      all previously reported studies of hyponatremia in patients with NMOSDs and
      propose several potential pathophysiological mechanisms of hyponatremia. In
      conclusion, NMOSDs accompanied by hyponatremia are not actually rare, but have
      previously been given little attention. Furthermore, SIADH should not be the only
      consideration, before the exclusion of rare but significant CSWS.

PMID- 29654709
TI  - 13 C Kinetic Isotope Effects as a Quantitative Probe To Distinguish between Enol
      and Enamine Mechanisms in Aminocatalysis.
AB  - A combination of experimental 13 C kinetic isotope effects (KIEs) and high-level
      density functional theory (DFT) calculations is used to distinguish between
      "enamine" and "enol" mechanisms in the Michael addition of acetone to trans-beta
      nitrostyrene catalyzed by Jacobsen's primary amine thiourea catalyst. In light of
      the recent findings that the widely used 18 O-incorporation probe for these
      mechanisms is flawed, the results described in this communication demonstrate an
      alternative probe to distinguish between these pathways. A key advantage of this
      probe is that quantitative mechanistic information is obtained without modifying
      experimental conditions. This approach is expected to find application in
      resolving mechanistic debates, while providing valuable information about the key
      transition state of organocatalyzed reactions involving the alpha
      functionalization of carbonyls.

PMID- 29654710
TI  - Similarities in temperature-dependent gene expression plasticity across
      timescales in threespine stickleback (Gasterosteus aculeatus).
AB  - Phenotypic plasticity occurs at a variety of timescales, but little is known
      about the degree to which plastic responses at different timescales are
      associated with similar underlying molecular processes, which is critical for
      assessing the effects of plasticity on evolutionary trajectories. To address this
      issue, we identified differential gene expression in response to developmental
      temperature in the muscle transcriptome of adult threespine stickleback
      (Gasterosteus aculeatus) exposed to 12, 18 and 24 degrees C until hatch and then
      held at 18 degrees C for 9 months and compared these results to differential gene
      expression in response to adult thermal acclimation in stickleback developed at
      18 degrees C and then acclimated to 5 and 25 degrees C as adults. Adult thermal
      acclimation affected the expression of 7,940 and 7,015 genes in response to cold
      and warm acclimation, respectively, and 4,851 of these genes responded in both
      treatments. In contrast, the expression of only 33 and 29 genes was affected by
      cold and warm development, respectively. The majority of the genes affected by
      developmental temperature were also affected by adult acclimation temperature.
      Many genes that were differentially expressed as a result of adult acclimation
      were associated with previously identified temperature-dependent effects on DNA
      methylation patterns, suggesting a role of epigenetic mechanisms in regulating
      gene expression plasticity during acclimation. Taken together, these results
      demonstrate similarities between the persistent effects of developmental
      plasticity on gene expression and the effects of adult thermal acclimation,
      emphasizing the potential for mechanistic links between plasticity acting at
      these different life stages.

PMID- 29654711
TI  - Development and validation of a novel score for fibrosis staging in patients with
      chronic hepatitis B.
AB  - BACKGROUND & AIMS: Non-invasive assessment methods for liver fibrosis are
      urgently needed. The present study aimed to develop a novel diagnostic model for
      fibrosis staging in patients with chronic hepatitis B. METHODS: A cross-sectional
      set of 417 chronic hepatitis B patients who underwent liver biopsy was enrolled
      and the METAVIR score was adopted as the reference of fibrosis staging. RESULTS:
      Among thyroid hormones, only the level of free tetraiodothyronine (FT4) decreased
      gradually with the METAVIR fibrosis score (P < .001). FibroStage, a novel
      diagnosis model that incorporates data on FT4, platelets, cholinesterase, gamma
      glutamyl transpeptidase, and age, was developed using the deriving set (n = 219).
      For the diagnosis of significant fibrosis, the FibroStage model had a
      significantly higher area under the receiver operating curve than did the
      FibroIndex, Forn, and Lok models (all of P < .01) and tended to better than the
      fibrosis-4 (P = .0791) but comparable with the aspartate transaminase-to-platelet
      ratio index model (P = .1694). For the diagnosis of advanced fibrosis, FibroStage
      had a higher area under the receiver operating curve than did the aspartate
      transaminase-to-platelet ratio index, FibroIndex, Forn, and Lok models (all of P
      < .05) and had a comparable area under the receiver operating curve with the
      fibrosis-4 model (P = .2109). For the diagnosis of cirrhosis, the area under the
      receiver operating curve of FibroStage was higher than those of the aspartate
      transaminase-to-platelet ratio index, fibrosis-4, FibroIndex, and Lok (all of P <
      .05) models and was comparable with Forn (P = .1649). These results was validated
      by a validation set (n = 198). CONCLUSION: FT4 may be an indicator for fibrosis
      staging in chronic hepatitis B patients. FibroStage is a better model than
      aspartate transaminase-to-platelet ratio index, fibrosis-4, FibroIndex, Forn, and
      Lok for the comprehensively diagnosis of significant and advanced fibrosis and
      cirrhosis.

PMID- 29654713
TI  - Glucose control and autonomic response during acute stress in youth with type 1
      diabetes: A pilot study.
AB  - BACKGROUND: Type 1 diabetes (T1D) is a chronic source of metabolic and
      neuropsychological stress, which may eventually lead to autonomic neuropathy and
      other complications related to micro- and macro-vasculopathies. We aimed to
      investigate the relationship between T1D chronic stress and autonomic response to
      acute stress testing that was expected being affected by chronic stress. METHODS:
      Twenty youths with confirmed diagnosis of T1D were assessed. Chronic stress
      assessment included hemoglobin A1c (HbA1c) >=7.5%, psychological stress assessed
      by perceived stress scale (PSS), hypoglycemic events, and proinflammatory
      cytokines. The acute stress testing used standardized stress video games.
      Autonomic response to acute stress was assessed by the amplitude and direction of
      changes in heart rate variability. Analyses determined correlations between
      changes in parasympathetic nervous system during stress testing and chronic
      diabetes stressors. RESULTS: A strong correlation was found between the amplitude
      of high frequency (HF) changes and HbA1c values (rho = 0.74, P < .001). Youths
      with HbA1c >=7.5% showed a larger amplitude of HF changes during acute stress
      (49% vs 16%, P < .001) and a higher PSS score (22.5 vs 19.0, P = .003), compared
      to those with HbA1c <7.5%. Additionally, among youths with HbA1c >=7.5%, those
      with positive changes in HF had a lower level of IL-8 than those with negative
      changes (5.40 vs 7.85 pg/mL, P = .009). CONCLUSIONS: Study findings support the
      need for better understanding the health effects of stress-related autonomic
      dysfunction in youth with T1D.

PMID- 29654714
TI  - The diverse origins of circulating cell-free DNA in the human body: a critical re
      evaluation of the literature.
AB  - Since the detection of cell-free DNA (cfDNA) in human plasma in 1948, it has been
      investigated as a non-invasive screening tool for many diseases, especially solid
      tumours and foetal genetic abnormalities. However, to date our lack of knowledge
      regarding the origin and purpose of cfDNA in a physiological environment has
      limited its use to more obvious diagnostics, neglecting, for example, its
      potential utility in the identification of predisposition to disease, earlier
      detection of cancers, and lifestyle-induced epigenetic changes. Moreover, the
      concept or mechanism of cfDNA could also have potential therapeutic uses such as
      in immuno- or gene therapy. This review presents an extensive compilation of the
      putative origins of cfDNA and then contrasts the contributions of cellular
      breakdown processes with active mechanisms for the release of cfDNA into the
      extracellular environment. The involvement of cfDNA derived from both cellular
      breakdown and active release in lateral information transfer is also discussed.
      We hope to encourage researchers to adopt a more holistic view of cfDNA research,
      taking into account all the biological pathways in which cfDNA is involved, and
      to give serious consideration to the integration of in vitro and in vivo
      research. We also wish to encourage researchers not to limit their focus to the
      apoptotic or necrotic fraction of cfDNA, but to investigate the intercellular
      messaging capabilities of the actively released fraction of cfDNA and to study
      the role of cfDNA in pathogenesis.

PMID- 29654715
TI  - Virgin coconut oil extract mitigates testicular-induced toxicity of alcohol use
      in antiretroviral therapy.
AB  - The consumption of alcohol by people living with HIV/AIDS is associated with a
      graver prognosis. Long-term use of antiretrovirals may have certain health
      challenges that may be aggravated by concomitant alcohol use. This study
      investigated virgin coconut oil (VCO) as an adjuvant to the deleterious effects
      of highly active antiretroviral therapy (HAART) and alcohol on the cyto
      architecture and functioning of the testis. Forty adult male Sprague-Dawley rats,
      weighing 165~176 g, were divided into eight groups and treated according to
      protocol. Testicular histology, stereological parameters, seminal fluid,
      testosterone, luteinizing hormone, follicle-stimulating hormone, the antioxidants
      marker malondialdehyde (MDA), and antioxidant glutathione (GSH) were examined.
      The use of ethanol alone and ethanol + HAART showed extensive degeneration in the
      seminiferous epithelium, decreased semen quality, disorganized basement membrane
      and widened, hypocellular interstitium. GSH was significantly decreased in the
      ethanol alone treated group with no significant effect on testosterone, LH, and
      MDA levels. Adjuvant treatment with VCO at low dose (2.5 mL/kg/bw) improved sperm
      motility with a partial restoration of the histopathological alterations. High
      doses of VCO (5.0 mL/kg/bw) showed greater improvement with respect to sperm
      counts, increased FSH hormonal and GSH antioxidant levels, and a well-preserved
      testicular cyto-architecture.

PMID- 29654716
TI  - Vascularization of colorectal carcinoma liver metastasis: insight into
      stratification of patients for anti-angiogenic therapies.
AB  - Current treatment for metastatic disease targets angiogenesis. With the
      increasing data demonstrating that cancer cells do not entirely rely on
      angiogenesis but hijack the existing vasculature through mechanisms such as co
      option of existing blood vessels, identification of targets has become of utmost
      importance. Our study looks at the vasculature of chemonaive and treated
      colorectal carcinoma liver metastases (CRCLMs) to obtain a basic understanding of
      the microvessel density, type of vasculature (mature versus immature), and
      correlation with histopathological growth patterns that demonstrate unique
      patterns of angiogenesis. We performed immunohistochemistry on chemonaive
      sections of desmoplastic histopathological growth pattern (DHGP) and replacement
      histopathological growth patterns (RHGP) lesions with CD31 [endothelial cell (EC)
      marker] and CD34/Ki67 double staining, which denotes proliferating ECs. The CD31
      stains demonstrated a lower microvascular CD31 +ve capillary density in the DHGP
      versus RHGP lesions; and integrating both immunostains with CD34/Ki67 staining on
      serial sections revealed proliferating vessels in DHGP lesions and co-option of
      mature existing blood vessels in RHGP lesions. Interestingly, upon treatment with
      chemotherapy and bevacizumab, the RHGP lesions showed no necrosis whereas the
      DHGP lesions had almost 100% necrosis of the cancer cells and in most cases there
      was a single layer of viable cancer cells, just under or within the desmoplastic
      ring. The survival of these cells may be directly related to spatial location and
      possibly a different microenvironment, which may involve adhesion to different
      extracellular matrix components and/or different oxygen/nutrient availability.
      This remains to be elucidated. We provide evidence that DHGP CRCLMs obtain their
      blood supply via sprouting angiogenesis whereas RHGP lesions obtain their blood
      supply via co-option of existing vasculature. Furthermore current treatment
      regimens do not affect RHGP lesions and although they kill the majority of the
      cancer cells in DHGP lesions, there are cells surviving within or adjacent to the
      desmoplastic ring which could potentially give rise to a growing lesion.

PMID- 29654717
TI  - Structure and dynamics of plant TatA in micelles and lipid bilayers studied by
      solution NMR.
AB  - The twin-arginine translocase (Tat) transports folded proteins across the
      cytoplasmic membrane of prokaryotes and the thylakoid membrane of plant
      chloroplasts. In Gram-negative bacteria and chloroplasts, the translocon consists
      of three subunits, TatA, TatB, and TatC, of which TatA is responsible for the
      actual membrane translocation of the substrate. Herein we report on the
      structure, dynamics, and lipid interactions of a fully functional C-terminally
      truncated 'core TatA' from Arabidopsis thaliana using solution-state NMR. Our
      results show that TatA consists of a short N-terminal transmembrane helix (TMH),
      a short connecting linker (hinge) and a long region with propensity to form an
      amphiphilic helix (APH). The dynamics of TatA were characterized using 15 N
      relaxation NMR in combination with model-free analysis. The TMH has order
      parameters characteristic of a well-structured helix, the hinge is somewhat less
      rigid, while the APH has lower order parameters indicating structural
      flexibility. The TMH is short with a surprisingly low protection from solvent,
      and only the first part of the APH is protected to some extent. In order to
      uncover possible differences in TatA's structure and dynamics in detergent
      compared to in a lipid bilayer, fast-tumbling bicelles and large unilamellar
      vesicles were used. Results indicate that the helicity of TatA increases in both
      the TMH and APH in the presence of lipids, and that the N-terminal part of the
      TMH is significantly more rigid. The results indicate that plant TatA has a
      significant structural plasticity and a capability to adapt to local
      environments.

PMID- 29654718
TI  - Socrates on Quality.

PMID- 29654719
TI  - Ethico-Legal Challenges of Drug Packing-A Case Report.

PMID- 29654720
TI  - Gender Differences in Antithrombotic Treatment for Newly Diagnosed Atrial
      Fibrillation: The GLORIA-AF Registry Program.
AB  - AIMS: Data on gender differences in oral anticoagulation for stroke prevention in
      patients with atrial fibrillation are conflicting, largely limited to regional
      reports and vitamin K antagonist use. We aimed to analyze gender-specific
      anticoagulant prescription patterns early following the introduction of non
      vitamin K antagonist oral anticoagulants (NOACs) in a large, global registry on
      atrial fibrillation. METHODS: The Global Registry on Long-Term Oral
      Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) is an
      international registry program involving patients with newly diagnosed atrial
      fibrillation (<3 months from arrhythmia onset). We used data from 15,092
      consecutive patients (median age, 71.0 years; 45.5% were women) enrolled between
      2011 and 2014. Globally, 79.7% of women and 80.2% of men were anticoagulated; the
      absolute between-gender difference in prevalence of anticoagulant use was -0.5%
      (95% confidence interval, -1.8% to 0.8%). Vitamin K antagonists were prescribed
      to 32.8% and 31.9% (NOACs 46.8% and 48.3%) of women and men, respectively.
      RESULTS: No confounder for the association between gender and anticoagulant
      prescription was identified. Between-gender differences in anticoagulant use
      (lower use in women compared with men by decreasing order of magnitude of the
      difference) were found for CHA2DS2-VASc (congestive heart failure, hypertension,
      age >=75 years, diabetes mellitus, stroke/transient ischemic attack, vascular
      disease, age 65-74 years, sex category [female]) score = 1; CHADS2 (congestive
      heart failure, hypertension, age >=75 years, diabetes mellitus, stroke) score =
      0; previous bleeding; age <65 years; no history of hypertension; myocardial
      infarction; coronary artery disease; North America region; and specialist office
      setting. CONCLUSION: Globally, the prevalence of anticoagulant use is similar in
      women and men. The decision to prescribe oral anticoagulation seems to depend
      predominantly on guideline-related differences in stroke risk stratification
      rather than on gender.

PMID- 29654722
TI  - Giant Mediastinal Liposarcoma: A Rare Yet Distinct Clinical Entity.
AB  - Mediastinal liposarcomas are rare tumors that occasionally present as unusually
      large and rapidly growing mediastinal masses resulting in compressive symptoms.
      We present a case of a 48-year-old woman undergoing resection of a mediastinal
      liposarcoma of massive proportion and propose that "giant mediastinal
      liposarcomas" be identified as a distinct clinical entity.

PMID- 29654721
TI  - Pleiotropic Role of p53 in Injury and Liver Regeneration after Acetaminophen
      Overdose.
AB  - p53 is the major cellular gatekeeper involved in proliferation, cell death,
      migration, and homeostasis. The role of p53 in pathogenesis of drug-induced liver
      injury is unknown. We investigated the role of p53 in liver injury and
      regeneration after acetaminophen (APAP) overdose, the most common cause of acute
      liver failure in the Western world. Eight-week-old male wild-type (WT) and p53
      knockout (p53KO) mice were treated with 300 mg/kg APAP, and the dynamics of liver
      injury and regeneration were studied over a time course of 0 to 96 hours.
      Deletion of p53 resulted in a threefold higher liver injury than in WT mice.
      Interestingly, despite higher liver injury, p53KO mice recovered similarly as the
      WT mice because of faster liver regeneration. Deletion of p53 did not affect APAP
      bioactivation and initiation of injury. Microarray analysis revealed that p53KO
      mice had disrupted metabolic homeostasis and induced inflammatory and
      proliferative signaling. p53KO mice showed prolonged steatosis correlating with
      prolonged liver injury. Initiation of liver regeneration in p53KO mice was
      delayed, but once initiated, cell cycle was significantly faster than WT mice
      because of sustained AKT, extracellular signal-regulated kinase, and mammalian
      target of rapamycin signaling. These studies show that p53 plays a pleotropic
      role after APAP overdose, where it prevents progression of liver injury by
      maintaining metabolic homeostasis and also regulates initiation of liver
      regeneration through proliferative signaling.

PMID- 29654723
TI  - Long-Term Outcome of Homograft Implants Related to Donor and Tissue
      Characteristics.
AB  - BACKGROUND: Cardiovascular homografts are used for right ventricular outflow
      tract reconstruction. The procedure has excellent survival rates, but many
      homografts degenerate and require reintervention. Studies analyzing risk factors
      for reintervention most often focus on recipient and homograft characteristics,
      with identification of risk factors such as young recipient age and the use of
      aortic homografts. This study focuses on less known variables, including donor
      characteristics and homograft management and its effect on long-term outcome of
      homograft implantation. METHODS: A retrospective study was conducted of 304
      patients undergoing right ventricular outflow tract reconstruction at University
      Hospital Lund, Sweden, between 1995 and 2008. Follow-up was up to 22 years.
      Donor, homograft, and recipient characteristics were analyzed. Statistical
      analyses included the Kaplan-Meier method with log-rank test and Cox proportional
      hazard regression. RESULTS: Follow-up was 98% complete. There were 12 deaths, and
      115 reinterventions were required. Younger donor age was identified as a risk
      factor. Homografts from multiorgan donors with no ischemic time produced the
      longest homograft survival. In non-heart-beating donors, long-term results did
      not differ between 1 and 24 hours of ischemic time and more than 24 hours of
      ischemic time. Longer retrieval to cryopreservation times seemed to be better
      compared with shorter time intervals. Long-term outcome was superior in
      homografts from middle-aged donors. CONCLUSIONS: The best long-term outcome was
      found when homografts were retrieved from organ donors and middle-aged donors.
      There is no harm extending the ischemic time in non-heart-beating donors to 48
      hours to increase the number of possible donors.

PMID- 29654724
TI  - Left Thoracotomy for Redo Mitral Valve Replacement in Giant Left Atrium and
      Severe Pectus Excavatum.

PMID- 29654725
TI  - Lung Cancer Screening: The True Benefit.

PMID- 29654726
TI  - Robotic Hybrid Approach for an Anterior Pancoast Tumor in a Severely Obese
      Patient.
AB  - Several different surgical approaches to anterior Pancoast tumors have been
      proposed. The osteomuscular-sparing transmanubrial approach allows optimal
      exposure and control of apical chest wall structures, but it requires an
      additional thoracotomy to perform the lobectomy with radical lymph node
      resection. The presented technique combines the osteomuscular-sparing
      transmanubrial approach with robotic-assisted upper lobectomy in a severely obese
      patient, thereby reducing the invasiveness of the surgical approach and the
      postoperative complications.

PMID- 29654727
TI  - Comparative proteomic analysis of human malignant ascitic fluids for the
      development of gastric cancer biomarkers.
AB  - OBJECTIVES: Malignant ascites is a sign of peritoneal seeding, which is one of
      the most frequent forms of incurable distant metastasis. Because the development
      of malignant ascites is associated with an extremely poor prognosis, determining
      whether it resulted from peritoneal seeding has critical clinical implications in
      diagnosis, choice of treatment, and active surveillance. At present, the
      molecular characterizations of malignant ascites are especially limited in case
      of gastric cancer. We aimed to identify malignant ascites-specific proteins that
      may contribute to the development of alternative methods for diagnosis and
      therapeutic monitoring and also increase our understanding of the pathophysiology
      of peritoneal seeding. DESIGN & METHODS: First, comprehensive proteomic
      strategies were employed to construct an in-depth proteome of ascitic fluids.
      Label-free quantitative proteomic analysis was subsequently performed to identify
      candidates that can differentiate between malignant ascitic fluilds of gastric
      cancer patients from benign ascitic fluids. Finally, two candidate proteins were
      verified by ELISA in 84 samples with gastric cancer or liver cirrhosis. RESULTS:
      Comprehensive proteome profiling resulted in the identification of 5347 ascites
      proteins. Using label-free quantification, we identified 299 proteins that were
      differentially expressed in ascitic fluids between liver cirrhosis and stage IV
      gastric cancer patients. In addition, we identified 645 proteins that were
      significantly expressed in ascitic fluids between liver cirrhosis and gastric
      cancer patients with peritoneal seeding. Finally, Gastriscin and Periostin that
      can distinguish malignant ascites from benign ascites were verified by ELISA.
      CONCLUSIONS: This study identified and verified protein markers that can
      distinguish malignant ascites with or without peritoneal seeding from benign
      ascites. Consequently, our results could be a significant resource for gastric
      cancer research and biomarker discovery in the diagnosis of malignant ascites.

PMID- 29654729
TI  - Performance specifications and six sigma theory: Clinical chemistry and industry
      compared.
AB  - Analytical performance specifications are crucial in test development and quality
      control. Although consensus has been reached on the use of biological variation
      to derive these specifications, no consensus has been reached which model should
      be preferred. The Six Sigma concept is widely applied in industry for quality
      specifications of products and can well be compared with Six Sigma models in
      clinical chemistry. However, the models for measurement specifications differ
      considerably between both fields: where the sigma metric is used in clinical
      chemistry, in industry the Number of Distinct Categories is used instead. In this
      study the models in both fields are compared and discussed.

PMID- 29654728
TI  - Evaluation of Cobas 8000(r) for the quantification of albumin and IgG in serum
      and cerebrospinal fluid.
AB  - According to the 2017 revised McDonald criteria, the presence of oligoclonal
      bands (OCB) at isoelectric focusing (IEF) is useful for the diagnosis of Multiple
      Sclerosis (MS), including relapsing-remitting MS and primary progressive MS. In
      this context, the quantification of IgG in serum and CSF is required for IEF
      execution (to deposit the same amount of IgG in serum and CSF), while the
      quantification of albumin in serum and CSF allows the calculation of the albumin
      quotient. We have evaluated the analytical performances of Cobas 8000(r) analyzer
      for the quantification of albumin and IgG in serum and CSF. Coefficients of
      variation were below 3.3% for within-run precision and below 3.1% for between-run
      precision. Results were similar or better than those obtained on nephelometer
      Immage 800(r) and turbidimeter SPAPLUS(r). The uncertainty of quantification of
      IgG in CSF was 9% and that of albumin in CSF was 12%. IgG and albumin measured on
      Cobas 8000(r) in serum and CSF showed good agreement with results obtained on the
      nephelometer Immage 800(r), including for the classification of albumin quotient
      and CSF IgG index as normal or pathological. Therefore, Cobas 8000(r) is a
      valuable tool for the quantification of IgG and albumin in CSF, in the context of
      diagnosis of MS and other inflammatory disease affecting the central nervous
      system.

PMID- 29654730
TI  - Carotenoid esters analysis and occurrence: What do we know so far?
AB  - Carotenoids possessing hydroxyl groups can be found in nature both as free
      xanthophylls and as carotenoid esters, i.e. acylated with fatty acids. A single
      carotenoid can be acylated with different fatty acids, resulting in a high number
      of possible structures of carotenoid esters. The analysis of carotenoid esters
      can be challenging; although extraction techniques are essentially the same as
      those used for free carotenoids, depending on the sample composition, interfering
      compounds such as triacylglycerides are also present in the extract in
      significant amounts to cause high background noise and ionization suppression in
      mass spectrometric analysis. Besides analysis of UV-visible spectrum features,
      identification of carotenoid esters must include tandem mass spectrometry (MSn)
      because no changes in the carotenoid molecule chromophore occur due to acylation
      with fatty acids. Although carotenoid esters are widespread found in foods,
      especially in fruits, and their bioavailability is equivalent or even higher than
      that of the free carotenoid, occurrence of xanthophyll esters is very limited in
      human plasma and tissues. Challenges and further investigations needed on the
      topics above are given in this review.

PMID- 29654733
TI  - Cortical remodeling after electroacupuncture therapy in peripheral nerve
      repairing model.
AB  - Electroacupuncture (EA) is an alternative therapy for peripheral nerve injury
      (PNI). The treatment relies on post-therapeutic effect rather than real-time
      effect. We utilized fMRI to clarify the resting-state alteration caused by
      sustained effect of EA on peripheral nerve repairing model. Twenty-four rats were
      divided equally into three groups: normal group, model group and intervention
      group. Rats of the model and intervention group underwent sciatic nerve
      transection and direct anastomosis. EA intervention at ST-36 and GB-30 was
      conducted continuously for 4 months on the intervention group. Behavioral
      assessments and fMRI were performed 1 month and 4 months after surgery.
      Intervention group showed significant improvement on the gait parameters max
      contact mean intensity (MCMI) and thermal withdrawal latency (TWL) than model
      group. EA-related sustained effects of amplitude of low frequency fluctuations
      (ALFF) could be described as a remolding pattern of somatosensory area and
      sensorimotor integration regions which presented higher ALFF in the contralateral
      hemisphere and lower in the ipsilateral hemisphere than model group.
      Interhemispheric functional connectivity (FC) analysis showed a significantly
      lower FC after EA therapy between the largest significantly different clusters in
      bilateral somatosensory cortices than the model group 4 months after surgery(p <
      0.05). And the model group presented significantly higher FC than the normal
      group at both two time-points (p < 0.01). The sustained effect of EA on
      peripheral nerve repairing rats appeared to induce both regional and extensive
      neuroplasticity in bilateral hemispheres. We proposed that such EA-related effect
      was a reverse of maladaptive plasticity caused by PNI.

PMID- 29654732
TI  - First report of Anaplasma phagocytophilum infection in Holstein cattle in the
      Republic of Korea.
AB  - Global warming has increased the incidence and risk of tick-borne diseases in
      domestic animals and humans in the Republic of Korea (ROK). In this study, we
      investigated the prevalence of Anaplasma phagocytophilum in Holstein cattle (n =
      214) in the ROK using specific PCR assays. A. phagocytophilum infection was
      detected in only two animals (0.93%, 2/214). Our findings showed that PCR assay
      using the 16S rRNA gene, but not groEL, was suitable for detection of A.
      phagocytophilum in cattle. Phylogenetic analysis based on the16S rRNA gene showed
      that A. phagocytophilum was divided into two clades. Clade 1 included Korean
      isolates, such as those from dogs, cats, Korean water deer, and ticks, while A.
      phagocytophilum identified in Holstein cattle formed clade 2. Our results suggest
      that there is genetic variability among isolates of A. phagocytophilum
      circulating in the ROK. This is the first study to report A. phagocytophilum
      infection in Holstein cattle in the ROK. As A. phagocytophilum has zoonotic
      potential, additional epidemiological studies are needed to investigate the
      prevalence and genetic characterization of A. phagocytophilum from different
      regions and hosts.

PMID- 29654734
TI  - Editorial Comment.

PMID- 29654731
TI  - Lutein, zeaxanthin and mammalian development: Metabolism, functions and
      implications for health.
AB  - It is now widely accepted that nutrition during critical periods in early
      development, both pre- and postnatal, may have lifetime consequences in
      determining health or onset of major diseases in the adult life. Dietary
      carotenoids have shown beneficial health effects throughout the life cycle due to
      their potential antioxidant properties, their ability to serves as precursors of
      vitamin A and to the emerging signaling functions of their metabolites. The non
      provitamin A carotenoids lutein and zeaxanthin are emerging as important
      modulators of infant and child visual and cognitive development, as well as
      critical effectors in the prevention and treatment of morbidity associated with
      premature births. This review provides a general overview of lutein and
      zeaxanthin metabolism in mammalian tissues and highlights the major advancements
      and remaining gaps in knowledge in regards to their metabolism and health effects
      during pre- and early post-natal development. Furthering our knowledge in this
      area of research will impact dietary recommendation and supplementation
      strategies aimed at sustaining proper fetal and infant growth.

PMID- 29654735
TI  - Editorial Comment.

PMID- 29654736
TI  - Reply by Authors.

PMID- 29654737
TI  - There is insufficient evidence to claim that cerclage is the treatment of choice
      for patients with a cervical length <10 mm.

PMID- 29654738
TI  - Genetic and Phenotypic Traits of Staphylococcus Epidermidis Strains Causing
      Postcataract Endophthalmitis Compared to Commensal Conjunctival Flora.
AB  - PURPOSE: The aim of this study was to compare the virulence and antibiotic
      resistance traits of Staphylococcus epidermidis strains causing acute
      postcataract endophthalmitis to those isolated from the conjunctiva of uninfected
      control patients. DESIGN: Case-control study. METHODS: We isolated an S
      epidermidis strain from each of the 22 endophthalmitis patients, and from 43 of
      the 72 controls. Species identification was confirmed using both Matrix-assisted
      laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry and tuf
      gene amplification and sequencing. Antibiotic susceptibilities were evaluated
      using the AST-P631 card and the Vitek II automated system. The S epidermidis
      strains were tested for the presence of 7 virulence genes (icaA, icaB, icaC,
      icaD, atlE, aap, and capA), the insertion sequence IS256, and the mecA gene.
      RESULTS: The S epidermidis strains from the endophthalmitis patients displayed
      higher prevalence rates for aap, atlE, and mecA gene carriage compared to those
      of the control group (77% vs 42%, P = .007; 100% vs 79%, P = .02; and 54% vs 11%,
      P < .001, respectively). They also harbored the combination of the mecA and icaA
      genes more frequently compared to the control group (13% vs 2%, P = .01). They
      were significantly more resistant than control strains to methicillin,
      fluoroquinolones, and the aminoglycosides. CONCLUSIONS: A higher capacity of
      adhesion to the intraocular lens and formation of biofilms as well as greater
      resistance to antibiotics were found in S epidermidis strains causing
      postcataract endophthalmitis. The usefulness of such virulence and antibiotic
      resistance markers warrants further evaluation for prevention, treatment, and
      prognostic evaluation of S epidermidis endophthalmitis.

PMID- 29654739
TI  - Fifty years of ERCP: a personal review.

PMID- 29654741
TI  - RHBDF1 regulates APC-mediated stimulation of the epithelial-to-mesenchymal
      transition and proliferation of colorectal cancer cells in part via the Wnt/beta
      catenin signalling pathway.
AB  - The human rhomboid family-1 gene (RHBDF1) is an oncogene in breast and head and
      neck squamous cancers. Here, we show that RHBDF1 plays a significant role in
      colorectal cancer (CRC) formation and that the RHBDF1 expression level is higher
      in CRC than in corresponding normal tissues. Moreover, RHBDF1 promotes cell
      proliferation, invasion and migration in vitro. Furthermore, through
      overexpression and silencing of RHBDF1 and the mediator complex, our study
      demonstrates that RHBDF1 may positively regulate adenomatous polyposis coli (APC)
      in the Wnt/beta-catenin signalling pathway to increase the expression levels of
      MMP-14 and Twist, which act as important epithelial-to-mesenchymal transition
      (EMT) stimulating factors. Additionally, RHBDF1 may regulate c-myc and CyclinD1
      expression to influence cell proliferation. Finally, RHBDF1 overexpression and
      silencing influence CRC growth in BALB/c nude mice. In summary, our findings
      demonstrate that the regulatory effects of RHBDF1 on EMT and on cell
      proliferation are partially attributable to the Wnt/beta-catenin signalling
      pathway.

PMID- 29654742
TI  - The E3 ligase for metastasis associated 1 protein, TRIM25, is targeted by
      microRNA-873 in hepatocellular carcinoma.
AB  - Tumor metastasis accounts for 90% of all cancer-related deaths. Epithelial to
      mesenchymal transition (EMT) considered to be centrally important in acquired
      resistance to chemotherapy and in progression of tumors to secondary organs. One
      of the important mediators of metastatic progression in hepatocellular carcinoma
      (HCC) is the metastasis associated protein 1 (MTA-1). We have earlier shown that
      in the context of HCC and normal liver cell lines, MTA-1 protein is actively
      stabilized in HCC cell lines and actively degraded in normal liver cells. We have
      also shown that TRIM25 is the E3 ligase that interacts with and degrades MTA-1
      protein. The identity of the factor regulating expression of TRIM25 in normal
      liver cells and HCC is unknown. In the current work we elucidate that microRNA
      (miR)- 873 targets TRIM25 in HCC cells. Both metagenomic analysis and
      quantification of miR-873 and TRIM25 in 25 HCC patients revealed an inverse
      correlation between the two in HCC patients with high miR-873 and low TRIM25
      expression, respectively. The expression pattern was mimicked in the normal liver
      cells THLE-2 and the HCC cell line, HuH6. In vitro luciferase reporter assays
      confirmed TRIM25 as the target of miR-873. Transient transfection of HuH6 cells
      with an anti-miR-873 antagomir significantly decreased both transwell motility in
      these cells. Furthermore, in in vivo xenograft assays treatment with anti-miR-873
      antagomir significantly decreased hepatic nodules formation. Cumulatively, our
      data indicate that suppression of TRIM25 expression by high levels of miR-873
      dictates MTA1 protein upregulation in HCC.

PMID- 29654743
TI  - Characterization of therapeutic antibodies in the presence of human serum
      proteins by AU-FDS analytical ultracentrifugation.
AB  - The preclinical characterization of biopharmaceuticals seeks to determine the
      stability, state of aggregation, and interaction of the antibody/drug with other
      macromolecules in serum. Analytical ultracentrifugation is the best experimental
      method to understand these factors. Sedimentation velocity experiments using the
      AU-FDS system were performed in order to quantitatively characterize the
      nonideality of fluorescently labeled therapeutic antibodies in high
      concentrations of human serum proteins. The two most ubiquitous serum proteins
      are human serum albumin, HSA, and gamma-globulins, predominantly IgG. Tracer
      experiments were done pairwise as a function of HSA, IgG, and therapeutic
      antibody concentration. The sedimentation coefficient for each fluorescently
      labeled component as a function of the concentration of the unlabeled component
      yields the hydrodynamic nonideality (ks). This generates a 3x3 matrix of ks
      values that describe the nonideality of each pairwise interaction. The ks matrix
      is validated by fitting both 2:1 mixtures of HSA (1-40 mg/ml) and IgG (0.5-20
      mg/ml) as serum mimics, and human serum dilutions (10-100%). The data are well
      described by SEDANAL global fitting with the ks nonideality matrix. The ks values
      for antibodies are smaller than expected and appear to be masked by weak
      association. Global fitting to a ks and K2 model significantly improves the fits.

PMID- 29654744
TI  - Metabolism of fructose in B-cells: A 13C NMR spectroscopy based stable isotope
      tracer study.
AB  - Earlier studies on glucose metabolism in B-cells suggested an active TCA cycle in
      both naive B cells and differentiated IgA plasma cells. Glycolysis was shown to
      be more active in IgA plasma cells than naive B-cells. There have been no reports
      on the metabolism of fructose in B-cells. Fructose is a major sugar present in
      the western diet. Thus, we have investigated the metabolism of fructose in B
      cells including the effect of glucose on the metabolism of fructose. In this
      study, using 13C NMR spectroscopy and [U-13C]fructose and [U-13C]glucose as
      stable 13C isotope tracers, we investigated the metabolic fate of fructose and
      glucose in B-cells. B-cells showed mitochondrial oxidation of fructose when
      administered alone, but showed diminished oxidation of fructose in the presence
      of glucose. On the other hand, fructose did not significantly affect the
      mitochondrial metabolism of glucose.

PMID- 29654740
TI  - Next-generation proteasome inhibitors for cancer therapy.
AB  - Over 2 decades ago, the proteasome was considered a risky or even untenable
      therapeutic target. Today, proteasome inhibitors are a mainstay in the treatment
      of multiple myeloma (MM) and have sales in excess of 3 billion US dollars
      annually. More importantly, the availability of proteasome inhibitors has greatly
      improved the survival and quality of life for patients with MM. Despite the
      remarkable success of proteasome inhibitor therapies to date, the potential for
      improvement remains, and the development and optimal use of proteasome inhibitors
      as anticancer agents continues to be an active area of research. In this review,
      we briefly discuss the features and limitations of the 3 proteasome inhibitor
      drugs currently used in the clinic and provide an update on current efforts to
      develop next-generation proteasome inhibitors with the potential to overcome the
      limitations of existing proteasome inhibitor drugs.

PMID- 29654745
TI  - WDR1-regulated actin dynamics is required for outflow tract and right ventricle
      development.
AB  - Outflow tract (OFT) anomalies account for about 30% of human congenital heart
      defects detected at birth. The second heart field (SHF) progenitors contribute to
      OFT and right ventricle (RV) development, but the process largely remains
      unknown. WDR1 (WD-repeat domain 1) is a major co-factor of actin depolymerizing
      factor (ADF)/cofilin that actively disassembles ADF/cofilin-bound actin
      filaments. Its function in embryonic heart development has been unknown. Using
      Wdr1 floxed mice and Nkx2.5-Cre, we deleted Wdr1 in embryonic heart
      (Wdr1F/F;Nkx2.5-Cre) and found that these mice exhibited embryonic lethality, and
      hypoplasia of OFT and RV. To investigate the role of WDR1 in OFT and RV
      development, we generated SHF progenitors-specific Wdr1 deletion mice (shfKO).
      shfKO mice began to die at embryonic day 11.5 (E11.5), and displayed decreased
      size of the proximal OFT and RV at E10.5. In shfKO embryos, neither the number of
      SHF cells deployment to OFT nor cell proliferation and the cell number were
      changed, whereas the cellular organization and myofibrillar assembly of
      cardiomyocytes were severely disrupted. In the proximal OFT and RV of both shfKO
      and Wdr1F/F;Nkx2.5-Cre embryos, cardiomyocytes were dissociated from the outer
      compact myocardial layer and loosely and disorderly arranged into multilayered
      myocardium. Our results demonstrate that WDR1 is indispensable for normal OFT and
      RV development, and suggest that WDR1-mediated actin dynamics functions in
      controlling the size of OFT and RV, which might through regulating the spatial
      arrangement of cardiomyocytes.

PMID- 29654746
TI  - The role of the notochord in amniote vertebral column segmentation.
AB  - The vertebral column is segmented, comprising an alternating series of vertebrae
      and intervertebral discs along the head-tail axis. The vertebrae and outer
      portion (annulus fibrosus) of the disc are derived from the sclerotome part of
      the somites, whereas the inner nucleus pulposus of the disc is derived from the
      notochord. Here we investigate the role of the notochord in vertebral patterning
      through a series of microsurgical experiments in chick embryos. Ablation of the
      notochord causes loss of segmentation of vertebral bodies and discs. However, the
      notochord cannot segment in the absence of the surrounding sclerotome. To test
      whether the notochord dictates sclerotome segmentation, we grafted an ectopic
      notochord. We find that the intrinsic segmentation of the sclerotome is dominant
      over any segmental information the notochord may possess, and no evidence that
      the chick notochord is intrinsically segmented. We propose that the segmental
      pattern of vertebral bodies and discs in chick is dictated by the sclerotome,
      which first signals to the notochord to ensure that the nucleus pulposus develops
      in register with the somite-derived annulus fibrosus. Later, the notochord is
      required for maintenance of sclerotome segmentation as the mature vertebral
      bodies and intervertebral discs form. These results highlight differences in
      vertebral development between amniotes and teleosts including zebrafish, where
      the notochord dictates the segmental pattern. The relative importance of the
      sclerotome and notochord in vertebral patterning has changed significantly during
      evolution.

PMID- 29654748
TI  - Vaccine refusal - what we need to know.
AB  - OBJECTIVE: Opposition to vaccines is not a new event, and appeared soon after the
      introduction of the smallpox vaccine in the late 18th century. The purpose of
      this review is to educate healthcare professionals about vaccine hesitancy and
      refusal, its causes and consequences, and make suggestions to address this
      challenge. SOURCE OF DATA: A comprehensive and non-systematic search was carried
      out in the PubMed, LILACS, and ScieLo databases from 1980 to the present day,
      using the terms "vaccine refusal," "vaccine hesitancy," and "vaccine confidence."
      The publications considered as the most relevant by the author were critically
      selected. SYNTHESIS OF DATA: The beliefs and arguments of the anti-vaccine
      movements have remained unchanged in the past two centuries, but new social media
      has facilitated the dissemination of information against vaccines. Studies on the
      subject have intensified after 2010, but the author did not retrieve any
      published studies to quantify this behavior in Brazil. The nomenclature on the
      subject (vaccine hesitancy) was standardized by the World Health Organization in
      2012. Discussions have been carried out on the possible causes of vaccine
      hesitancy and refusal, as well as on the behavior of families and health
      professionals. Proposals for interventions to decrease public doubts, clarify
      myths, and improve confidence in vaccines have been made. Guides for the health
      care professional to face the problem are emerging. CONCLUSIONS: The healthcare
      professional is a key element to transmit information, resolve doubts and
      increase confidence in vaccines. They must be prepared to face this new
      challenge.

PMID- 29654749
TI  - Differences in cortisol concentrations in adolescents with eating disorders: a
      systematic review.
AB  - OBJECTIVE: To perform a systematic review of the literature for scientific
      evidence of possible differences in cortisol concentrations in adolescents with
      eating disorders. SOURCE OF DATA: Electronic searches were conducting in the
      PubMed, Scientific Electronic Library Online, Virtual Health Library, and Science
      Direct databases for articles published between 2007 and 2017 using the keywords,
      cortisol, hydrocortisone; eating disorders, bulimia, bulimia nervosa, anorexia,
      anorexia nervosa; adolescence, adolescent, adolescents. SYNTHESIS OF DATA: A
      total of 192 articles were found. After the analysis of the eligibility criteria
      using the PRISMA method, 19 articles were selected for the present review. Most
      studies were conducted in Europe. Adolescents diagnosed with anorexia nervosa
      were evaluated in all studies, except one, when other eating disorders were
      investigated. Blood was the means used for the determination of cortisol. In ten
      studies, cortisol levels were higher in the group with anorexia than the control
      group and a reduction in cortisol levels occurred in the adolescents after being
      submitted to nutritional recovery. CONCLUSIONS: Patients with eating disorders
      may have several clinical consequences, such as changes in body fat distribution,
      changes in bone mineral density, worsening of neurocognitive ability, and
      endocrine changes (e.g., hypercortisolemia), which in turn can lead to
      hyperglycemia, insulin resistance, hypertension, and increased risk of
      infections. The findings demonstrate that adolescents with eating disorders,
      especially anorexia nervosa, have increased cortisol levels, which are reduced
      after the treatment period. Further studies on differences in cortisol
      concentrations in adolescents with other eating disorders are needed, using
      different methods.

PMID- 29654750
TI  - Emergency contraception in Albania: a multimethods qualitative study of
      awareness, knowledge, attitudes and practices.
AB  - OBJECTIVES: Contraceptive prevalence is relatively low in Albania, and abortion
      is the mainstay of family planning. Although levonorgestrel-only emergency
      contraceptive pills are available, uptake of this method is minimal. Emergency
      contraception (EC) could play a significant role in addressing women's need for
      an effective and discreet pregnancy prevention method. However, information about
      the dynamics surrounding EC is limited. STUDY DESIGN: In 2016-2017, we conducted
      a multimethods qualitative study that aimed to explore awareness, knowledge,
      attitudes and practices toward EC in Albania. This project comprised four
      components: a community-based survey with 115 respondents, six focus group
      discussions with women of reproductive age, 19 semistructured key informant
      interviews, and 16 structured interviews with retail pharmacists. We analyzed our
      data using descriptive statistics and for content and themes. RESULTS: Our
      findings suggest that EC is widely available in pharmacies in Albania. However, a
      quarter of our survey participants did not know whether EC was available, and
      more than a third did not think EC was safe to use. Women face numerous barriers
      to accessing this form of contraception. Misconceptions about hormonal
      contraceptives, in general, and about progestin-only EC in particular, lack of
      training among providers, and stigma and fear of judgment were common obstacles
      identified by participants. CONCLUSIONS: Misinformation and lack of knowledge
      about EC among women and providers in Albania appears common. Training health
      service providers, raising awareness among women, and developing linguistically
      and culturally resonant materials for distribution could be keys to improving
      access to and use of EC. IMPLICATIONS: Although the availability of progestin
      only EC is widespread in Albania, our findings suggest that more work needs to be
      done to align national regulatory policies with international standards,
      facilitate evidence-based service delivery, and increase access to medically
      accurate information in Albanian.

PMID- 29654747
TI  - Advances in Evaluation of Chronic Diarrhea in Infants.
AB  - Diarrhea is common in infants (children less than 2 years of age), usually acute,
      and, if chronic, commonly caused by allergies and occasionally by infectious
      agents. Congenital diarrheas and enteropathies (CODEs) are rare causes of
      devastating chronic diarrhea in infants. Evaluation of CODEs is a lengthy process
      and infrequently leads to a clear diagnosis. However, genomic analyses and the
      development of model systems have increased our understanding of CODE
      pathogenesis. With these advances, a new diagnostic approach is needed. We
      propose a revised approach to determine causes of diarrhea in infants, including
      CODEs, based on stool analysis, histologic features, responses to dietary
      modifications, and genetic tests. After exclusion of common causes of diarrhea in
      infants, the evaluation proceeds through analyses of stool characteristics
      (watery, fatty, or bloody) and histologic features, such as the villus to crypt
      ratio in intestinal biopsies. Infants with CODEs resulting from defects in
      digestion, absorption, transport of nutrients and electrolytes, or
      enteroendocrine cell development or function have normal villi to crypt ratios;
      defects in enterocyte structure or immune-mediated conditions result in an
      abnormal villus to crypt ratios and morphology. Whole-exome and genome sequencing
      in the early stages of evaluation can reduce the time required for a definitive
      diagnosis of CODEs, or lead to identification of new variants associated with
      these enteropathies. The functional effects of gene mutations can be analyzed in
      model systems such as enteroids or induced pluripotent stem cells and are
      facilitated by recent advances in gene editing procedures. Characterization and
      investigation of new CODE disorders will improve management of patients and
      advance our understanding of epithelial cells and other cells in the intestinal
      mucosa.

PMID- 29654751
TI  - Continuation of injectable contraception when self-injected vs. administered by a
      facility-based health worker: a nonrandomized, prospective cohort study in
      Uganda.
AB  - OBJECTIVE: The purpose of this study was to compare 12-month continuation rates
      for subcutaneous depot medroxyprogesterone acetate (DMPA-SC) administered via
      self-injection and DMPA-IM administered by a health worker in Uganda. STUDY
      DESIGN: Women seeking injectable contraception at participating health facilities
      were offered the choice of self-injecting DMPA-SC or receiving an injection of
      DMPA-IM from a health worker. Those opting for self-injection were trained one-on
      one. They self-injected under supervision and took home three units, a client
      instruction guide and a reinjection calendar. Those opting for DMPA-IM received
      an injection and an appointment card for the next facility visit in 3 months. We
      interviewed participants at baseline (first injection) and after 3 (second
      injection), 6 (third injection) and 9 (fourth injection) months, or upon
      discontinuation. We used Kaplan-Meier methods to estimate continuation
      probabilities, with a log-rank test to compare differences between groups. A
      multivariate Cox regression identified factors correlated with discontinuation.
      RESULTS: The 12-month continuation rate for the 561 women self-injecting DMPA-SC
      was .81 [95% confidence interval (CI) .78-.84], and for 600 women receiving DMPA
      IM from a health worker, it was .65 (95% CI .61-.69), a significant difference at
      the .05 level. There were no differences in pregnancy rates or side effects. The
      multivariate analysis revealed that, controlling for covariates, self-injecting
      reduced the hazard for discontinuing by 46%. A significant interaction between
      injection group and age suggests that self-injection may help younger women
      continue injectable use. CONCLUSIONS: The significant difference in 12-month
      continuation between women self-injecting DMPA-SC and women receiving DMPA-IM
      from a health worker - which remains significant in a multivariate analysis -
      suggests that self-injection may improve injectable contraceptive continuation.
      IMPLICATIONS: While injectable contraceptives are popular throughout much of sub
      Saharan Africa, they have high rates of discontinuation. This study is the second
      from an African country to demonstrate that self-injection may improve injectable
      continuation rates and may do so without increasing the risk of pregnancy or
      adverse events.

PMID- 29654752
TI  - Role of acid responsive genes in the susceptibility of Escherichia coli to
      ciclopirox.
AB  - Antibiotic resistance poses a huge threat to the effective treatment of bacterial
      infections. To circumvent the limitations in developing new antibiotics,
      researchers are attempting to repurpose pre-developed drugs that are known to be
      safe. Ciclopirox, an off-patent antifungal agent, inhibits the growth of Gram
      negative bacteria, and genes involved in galactose metabolism and
      lipopolysaccharide (LPS) biosynthesis are plausible antibacterial targets for
      ciclopirox, since their expression levels partially increase susceptibility at
      restrictive concentrations. In the present study, to identify new target genes
      involved in the susceptibility of Escherichia coli to ciclopirox, genome-wide
      mRNA profiling was performed following ciclopirox addition at sublethal
      concentrations, and glutamate-dependent acid resistance (GDAR) genes were
      differentially regulated. Additional susceptibility testing, growth analyses and
      viability assays of GDAR regulatory genes revealed that down-regulation of evgS
      or hns strongly enhanced susceptibility to ciclopirox. Further microscopy and
      phenotypic analyses revealed that down-regulation of these genes increased cell
      size and decreased motility. Our findings could help to maximise the efficacy of
      ciclopirox against hard-to-treat Gram-negative pathogens.

PMID- 29654753
TI  - GSK126 alleviates the obesity phenotype by promoting the differentiation of
      thermogenic beige adipocytes in diet-induced obese mice.
AB  - A close relationship between epigenetic regulation and obesity has been
      demonstrated in several recent studies. Histone methyltransferase enhancer of
      Zeste homolog 2 (Ezh2), which mainly catalyzes trimethylation of histone H3K27 to
      form H3K27me3 was found to be required for the differentiation of white and brown
      adipocytes in vitro. Here, we investigated the effects of the Ezh2-specific
      inhibitor GSK126 in a mouse model of obesity induced by a high-fat diet (HFD). We
      found that GSK126 treatment reduced body fat, improved glucose tolerance,
      increased lipolysis and improved cold tolerance in mice by promoting the
      differentiation of thermogenic beige adipocytes. Moreover, we discovered that
      GSK126 inhibited the differentiation of white adipocytes, and the decrease of
      Ezh2 enzymatic activity and H3K27me3 also changed the morphology of brown
      adipocytes but did not alter the expression of thermogenic genes in these cells.
      Our results indicated that GSK126 was a novel chemical inducer of beige
      adipocytes and may be a potential therapeutic agent for the management of
      obesity. Furthermore, they also prompted that Ezh2 and H3K27me3 play different
      roles in the differentiation of the white, brown, and beige adipocytes in vivo.

PMID- 29654754
TI  - Sphingolipidomics analysis of large clinical cohorts. Part 1: Technical notes and
      practical considerations.
AB  - Lipids comprise an exceptionally diverse class of bioactive macromolecules. While
      quantitatively abundant lipid species serve fundamental roles in cell structure
      and energy metabolism, thousands of structurally-distinct, quantitatively minor
      species may serve as important regulators of cellular processes. Historically, a
      complete understanding of the biological roles of these lipids has been limited
      by a lack of sensitive, discriminating analytical techniques. The class of
      sphingolipids alone, for example, is known to consist of over 600 different
      confirmed species, but is likely to include tens of thousands of metabolites with
      potential biological significance. Advances in mass spectrometry (MS) have
      improved the throughput and discrimination of lipid analysis, allowing for the
      determination of detailed lipid profiles in large cohorts of clinical samples.
      Databases emerging from these studies will provide a rich resource for the
      identification of novel biomarkers and for the discovery of potential drug
      targets, analogous to that of existing genomics databases. In this review, we
      will provide an overview of the field of sphingolipidomics, and will discuss some
      of the challenges and considerations facing the generation of robust lipidomics
      databases.

PMID- 29654755
TI  - Cytoprotective role of ubiquitin against toxicity induced by polyglutamine
      expanded aggregates.
AB  - Ubiquitin (Ub) homeostasis is important for cellular function and survival,
      especially under stress conditions. Recently, we have demonstrated that Ubc-/-
      (Ub-deficient) mouse embryonic fibroblasts (MEFs) exhibited reduced viability
      under oxidative stress induced by arsenite, which was not due to dysregulation of
      the antioxidant response pathway, but rather due to the potential toxicity caused
      by the misfolded protein aggregates. However, it is still not clear whether Ub
      deficiency is directly related to the accumulation of toxic protein aggregates,
      as arsenite itself triggers protein aggregation and renders cells into aberrant
      conditions such as reduced proteasome function and inhibition of autophagic flux.
      Therefore, under arsenite treatment, the outcome could be derived from the
      combination of multiple defective pathways. Furthermore, it has also been
      suggested that ubiquitination status of misfolded proteins may not be important
      for the formation of inclusion bodies composed of misfolded protein aggregates.
      We therefore wondered whether Ub deficiency is sufficient to trigger the
      accumulation of toxic protein aggregates inside the cells. In this study, we
      ectopically expressed polyQ-expanded aggregates (Q103) in MEFs and observed
      inclusion body formation at the juxtanuclear region, which was independent of
      cellular Ub levels. In contrast to arsenite treatment, polyQ expression did not
      affect proteasome function. However, we observed an increased accumulation of
      Q103 aggregates in Ubc-/- MEFs, which was due to impaired autophagic clearance.
      Finally, we demonstrated that the increased accumulation of Q103 aggregates under
      Ub deficiency dramatically reduced the viability of cells. Therefore, our results
      suggest that the maintenance of proper levels of cellular Ub is important to
      protect cells against the toxicity induced by the accumulation of protein
      aggregates.

PMID- 29654756
TI  - PPM1B depletion in U2OS cells supresses cell growth through RB1-E2F1 pathway and
      stimulates bleomycin-induced cell death.
AB  - PPM1B is a metal-dependent serine/threonine protein phosphatase, with a similar
      structure and function to the well-known oncogene in breast cancer, PPM1D (WIP1).
      However, clinical significance of PPM1B as a pharmacological target in cancer
      therapy has not been explored. To test if PPM1B can be a drug target in the
      cellular proliferation and death pathway, the lentiviral PPM1B shRNA was stably
      expressed in cancer cell lines and its regulatory function in the RB1-E2F1
      pathway was examined. We found that PPM1B depletion suppressed cellular
      proliferation of U2OS cells, accompanied by hyper-phosphorylation of RB1 and up
      regulation of E2F1 target genes, p27 and caspase 7. Notably, PPM1B depletion
      significantly sensitised U2OS cells to bleomycin-induced cell death at a minimal
      effective concentration. Our results suggest that PPM1B plays a negative role in
      the activation of the p38-RB1-E2F1 pathway and that targeting PPM1B could be
      useful in certain types of cancer by stimulating chemotherapy-induced cell death.

PMID- 29654757
TI  - Sphingolipidomics analysis of large clinical cohorts. Part 2: Potential impact
      and applications.
AB  - It has been known for decades that the regulation of sphingolipids (SLs) is
      essential for the proper function of many cellular processes. However, a complete
      understanding of these processes has been complicated by the structural diversity
      of these lipids. A well-characterized metabolic pathway is responsible for
      homeostatic maintenance of hundreds of distinct SL species. This pathway is
      perturbed in a number of pathological processes, resulting in derangement of the
      "sphingolipidome." Recently, advances in mass spectrometry (MS) techniques have
      made it possible to characterize the sphingolipidome in large-scale clinical
      studies, allowing for the identification of specific SL molecules that mediate
      pathological processes and/or may serve as biomarkers. This manuscript provides
      an overview of the functions of SLs, and reviews previous studies that have used
      MS techniques to identify changes to the sphingolipidome in non-metabolic
      diseases.

PMID- 29654758
TI  - Regulation of hair follicle development by exosomes derived from dermal papilla
      cells.
AB  - BACKGROUND: Dermal papilla cells (DPCs) play a critical role in the regulation of
      hair follicle (HF) growth, formation, and cycling. DPCs are thought to regulate
      HF growth through a paracrine mechanism, in which exosomes may play a critical
      role. METHODS: DPC-Exos were cutaneously injected into HFs at different HF cycle
      stages and the effects were evaluated by histological and immunohistochemical
      analyses. The effects of DPC-Exos on proliferation, migration, and cell cycle
      status of outer root sheath cells (ORSCs) were evaluated. After treatment of DPC
      Exos, changes in mRNA and protein levels of beta-catenin and Sonic hedgehog (Shh)
      in ORSCs were detected. RESULTS: DPC-Exos were approximately 105 nm in diameter
      and expressed tumor susceptibility gene 101, cluster of differentiation (CD)9,
      and CD63. Injection of DPC-Exos accelerated the onset of HF anagen and delayed
      catagen in mice. Immunohistochemical analyses revealed that beta-catenin and Shh
      levels were upregulated in the skin. In vitro, DPC-Exo treatment enhanced ORSC
      proliferation and migration, and stimulated the expression of beta-catenin and
      Shh. CONCLUSION: DPC-Exos contribute to the regulation of HF growth and
      development, and provide a potential avenue for the treatment of hair loss.

PMID- 29654759
TI  - Small nucleolar RNA U2_19 promotes hepatocellular carcinoma progression by
      regulating Wnt/beta-catenin signaling.
AB  - Emerging evidence suggests that small nucleolar RNAs (snoRNAs) have
      malfunctioning roles in oncogenesis. In the present study, we investigated the
      role of box C/D small nucleolar RNA U2_19 (snoU2_19) in the tumorigenesis of
      hepatocellular carcinoma (HCC). Recently, we screened snoRNAs differential
      signatures by performing high-throughput small RNA sequence in HCC tissues and
      validated that upregulated snoU2_19 was associated with aggressive phenotypes in
      HCC patients. Aberrant snoU2_19 facilitated HCC cell proliferation, inhibited
      apoptosis and induced cell cycle progression in vitro analyses. We globally
      investigated the molecular mechanisms of snoU2_19 in HCC and found that snoU2_19
      knockdown inhibited Wnt/beta-catenin signaling pathway through inducing the
      translocation of beta-catenin in cytoplasm. We concluded that snoU2_19 plays a
      pathological role in the development and progression of HCC, and is a potential
      therapeutic target for HCC.

PMID- 29654760
TI  - Melanosome degradation in epidermal keratinocytes related to lysosomal protease
      cathepsin V.
AB  - The cause of hyperpigmentation, such as solar lentigo and seborrheic keratosis,
      is the excessive accumulation of melanin pigments in the epidermal basal layer.
      Melanin pigments are synthesized in the melanosomes, which are specific
      organelles produced by melanocytes in the basal layer. Melanosomes containing
      melanin pigments are transported to the neighboring keratinocytes. However, the
      behavior of melanosomes after being transported to the keratinocytes has been
      poorly understood. In this study, we focused on a lysosomal protease cathepsin V
      (CTSV) to clarify the mechanism underlying melanosome degradation in the
      keratinocytes. Using immunohistochemical observation, we found that CTSV was
      highly expressed across the entire epidermis in normal skin; however, CTSV
      expression levels were lower in the basal layer than those in the stratum corneum
      side in the hyperpigmented region. Moreover, we found that melanosome degradation
      was suppressed in CTSV knockdown cells. These results indicated that CTSV is
      involved in melanosome degradation.

PMID- 29654761
TI  - Particulate matter increases beta-amyloid and activated glial cells in
      hippocampal tissues of transgenic Alzheimer's mouse: Involvement of PARP-1.
AB  - Exposure to air pollutants, such as particulate matter (PM), has been implicated
      in neurodegenerative disorders including Alzheimer's disease (AD). However,
      direct effects of PM on production of beta-amyloid (Abeta), a key pathogenic
      molecule in AD, and its underlying mechanism are still elusive. Given PM's
      potential to induce oxidative stress in other tissues, we hypothesized that
      poly(ADP-ribose) polymerase (PARP-1) might be involved in PM-induced
      neurotoxicity. To address this, we used an ex vivo model of AD, the organotypic
      hippocampal slice tissue culture from old (12-14 months-of-age) triple transgenic
      3xTg-AD mice. First, we observed that fine PM (aerodynamic diameter < 4 MUm) can
      dose-dependently activate PARP-1 and decrease NAD+ levels in Neuro2A cells. PARP
      1 activation did occur under concentrations of PM which did not affect cell
      viability. Next, we observed that direct treatment of PM increased Abeta levels
      and activated glial cells in the ex vivo hippocampal tissues of 3xTg-AD mice. PM
      induced glial activation was most prominent in CA1 region of the hippocampal
      tissue. Notably, we found that pharmacological inhibition of PARP-1 reversed both
      PM-induced Abeta increase and glial activation, arguing the possible involvement
      of PARP-1 in PM-induced AD pathogenesis. Our findings suggest that PARP-1 might
      be a potential molecular target, responsible for mediating negative effects of PM
      on the brain. Modulating PARP-1 activity could be a promising approach to prevent
      or alleviate PM-related environmental neurotoxicity which could initiate AD
      pathogenesis.

PMID- 29654762
TI  - Egress of murine regulatory T cells from the thymus requires TIPE2.
AB  - Regulatory T cells (Tregs) can be divided into thymus-derived Treg (tTregs) and
      peripheral induced Tregs (pTregs) in vivo according to their origins and are
      essential for the maintenance of immune hemostasis and immune tolerance. Tumor
      necrosis factor-alpha-induced protein 8 like 2 (TIPE2) is expressed primarily by
      immune cells and is a negative regulator of the innate and adaptive immune
      response. Previous studies indicate that TIPE2 is required for the expression of
      Treg signature genes and promotes leading-edge formation in neutrophils through
      cytoskeleton remodeling. In the current study, we showed that TIPE2 deficient
      mice accumulate more Treg cells in the thymus. Further studies revealed that
      TIPE2 deficiency doesn't affect the development and apoptosis of tTregs. Instead,
      TIPE2 promotes the chemotaxis of tTregs in vitro, which may account for the
      accumulation of Tregs in the thymus of TIPE2 deficient mice. Mechanistic study
      revealed that TIPE2 promotes the polarization of pAKT and F-actin in tTregs
      undergoing directed migration. Taken together, these results demonstrated that
      TIPE2 enhances the cytoskeleton remodeling and promotes the thymus egress of
      tTregs, which may play an important role in the maintenance of self-tolerance.

PMID- 29654763
TI  - ST6GAL1 negatively regulates monocyte transendothelial migration and
      atherosclerosis development.
AB  - Monocyte transendothelial migration is a critical step in the initial stage of
      atherosclerosis, in which the involvement of alpha-2,6 sialyltransferase 1
      (ST6GAL1) has been confirmed by increasing evidence. But the direct relationship
      between ST6GAL1 and atherosclerosis remains incompletely uncertain. In this
      study, we demonstrated that the expression level of ST6GAL1 in vascular
      endothelium was significantly decreased in atherosclerosis development process,
      while obviously recovered after atherosclerosis regression. Further analysis
      showed that knockdown of ST6GAL1 by RNA interference in vascular endothelial
      cells EA. hy926 obviously promoted TNFalpha-triggered monocyte-transendothelial
      migration, whereas overexpression of ST6GAL1 strongly inhibited monocyte
      transendothelial migration. Moreover, we firstly found beta-catenin is a
      sialylated protein and its sialylation level is decreased in TNFalpha-treated EA.
      hy926 cells, suggesting that the function of ST6GAL1 in preventing both
      atherosclerosis development and monocyte transendothelial migration might result
      from the sialylation of beta-catenin of endothelium. Our results suggested
      ST6GAL1 might be a potential target for atherosclerosis prevention and treatment.

PMID- 29654764
TI  - Rg1 inhibits high glucose-induced mesenchymal activation and fibrosis via
      regulating miR-2113/RP11-982M15.8/Zeb1 pathway.
AB  - Recent study has showed that Ginsenoside Rg1, the mian active compound of Panax
      ginseng, could ameliorate oxidative stress and myocardial apoptosis in diabetes
      mellitus. However, the roles and mechanisms of Rg1 in proliferative diabetic
      retinopathy (PDR) are still unclear. In the present study, we aimed to
      investigate the effects of Rg1 on mesenchymal activation of high-glucose (HG)
      cultured muller cells. High glucose conditions up-regulate MMP-2, MMP-9 and down
      regulate TIMP-2, and promote mesenchymal activation in Muller cells. And Rg1
      inhibits the HG-induced mesenchymal activation and HG-increased MMP-2 and MMP-9
      and HG-decreased TIMP-2 in Muller cells. HG up-regulates Zeb1 and lncRNA RP11
      982M15.8, and down-regulates miR-2113, and Rg1 inhibits these effects of HG. Both
      inhibition of miR-2113 and over-expression of RP11-982M15.8 significantly
      restored the HG induced mesenchymal activasion. Taken together, our findings
      suggested that Rg1 inhibited HG-induced mesenchymal activation and fibrosis via
      regulating miR-2113/RP11-982M15.8/Zeb1 pathway.

PMID- 29654765
TI  - Adipose mesenchymal stem cell-derived exosomes stimulated by hydrogen peroxide
      enhanced skin flap recovery in ischemia-reperfusion injury.
AB  - BACKGROUND: Mesenchymal stem cell (MSC)-derived exosomes have been recognized as
      new candidates for the treatment of ischemic disease or injury and may be an
      alternative treatment for cell therapy. This aim of the study was to evaluate
      whether exosomes derived from adipose mesenchymal stem cell (ADSC) can protect
      the skin flap during ischemia-reperfusion (I/R) injury and induce
      neovascularization. METHODS: To investigate the effects of exosomes in the I/R
      injury of flap transplantation in vivo, flaps were subjected to 6 h of ischemia
      by ligating the left superficial inferior epigastric vessels (SIEA) followed by
      blood perfusion. Exosomes derived from normal ADSC (ADSC-exos) and exosomes
      derived from ADSC preconditioned with H2O2 (H2O2-ADSC-exos) were injected into
      the flaps. Then, the blood perfusion unit (BPU) of the flaps was measured by
      Laser Doppler Perfusion Imaging (LDPI) and microvessel density was determined by
      the endothelial with cell marker CD31 with Immunohistochemistry (IHC) staining.
      Inflammatory cell infiltration of the skin flap and apoptosis were detected by
      hematoxylin & eosin staining (H&E) and the TdT-mediated biotinylated dUTP nick
      end-labeling (TUNEL) technique. RESULTS: In vivo, exosomes significantly
      increased flap survival and capillary density compared to I/R on postoperative
      day 5, and decreased the inflammatory reaction and apoptosis in the skin flap (P
      < 0.05). Furthermore, H2O2-ADSC-exos had better outcomes compared to normal
      exosomes (P < 0.05). ADSC-exos could significantly increase human umbilical vein
      endothelial cell (HUVEC) proliferation (P < 0.05), but no statistic difference
      was found in exosomes derived from different microenvironments (P > 0.05). HUVEC
      co-cultured with H2O2-ADSC-exos increased the migration ratio and generated more
      cord-like structures compared to ADSC-exos and the control group (P < 0.05).
      CONCLUSION: ADSC-exos can enhance skin flap survival, promote neovascularization
      and alleviate the inflammation reaction and apoptosis in the skin flap after I/R
      injury. The use of a specific microenvironment for in vitro stem cell culture,
      such as one containing a low concentration of H2O2, will facilitate the
      development of customized exosomes for cell-free therapeutic applications in skin
      flap transplantation.

PMID- 29654766
TI  - Orai1 downregulation impairs lymphocyte function in type 2 diabetes mellitus.
AB  - BACKGROUND/AIMS: It has been suggested that diabetes is associated with immune
      dysfunction, in which Ca2+ signaling malfunction in lymphocyte may contributes
      most. However, the pattern of the Ca2+ signal disorder and the mechanism(s) that
      explains the change are unclear. Here, in this study we aimed to investigate
      possible changes and mechanism(s) accounting for the internal Ca2+ signals in
      diabetic T lymphocyte upon stimulation. METHODS AND RESULTS: Using Fura-2-AM, we
      found a significant decrease in Ca2+ influx induced by thapsigargin (TG) and anti
      CD3 antibody (OKT3) in T lymphocytes from blood of both diabetes patients and
      animals. Furthermore, a downregulated Orai1 protein expression, but not mRNA, was
      also observed in these cells using western blot and qRT-PCR, respectively. In
      addition, in high-glucose and agonist treated Jurkat T cells, Ca2+ entry and the
      release of interleukin-2 (IL-2) were also decreased. Orai1 expression reduced,
      while stromal interaction molecule 1 (STIM1) and other downstream proteins
      remained unchanged. CONCLUSION: This study demonstrates that the declined Orai1
      expression, at least partly, contributes to the downregulated Ca2+ entry during
      lymphocyte excitation, providing an important mechanism for T lymphocyte
      malfunction in diabetes.

PMID- 29654767
TI  - A novel small RNA S042 increases acid tolerance in Lactococcus lactis F44.
AB  - Lactococcus lactis, a gram-positive bacterium, encounters various environmental
      stresses, especially acid stress, during fermentation. Small RNAs (sRNAs) that
      serve as regulators at post-transcriptional level play important roles in acid
      stress response. Here, a novel sRNA S042 was identified by RNA-Seq, RT-PCR and
      Northern blot. The transcription level of s042 was upregulated 2.29-fold under
      acid stress by Quantitative RT-PCR (qRT-PCR) analysis. Acid tolerance assay
      showed that overexpressing s042 increased the survival rate of L. lactis F44 and
      deleting s042 significantly inhibited the viability under acidic conditions.
      Moreover, the targets were predicted by online software and four genes were
      chosen as candidates. Among them, argR (arginine regulator) and accD (acetyl-CoA
      carboxylase carboxyl transferase subunit beta) were validated to be the direct
      targets activated by S042 through reporter fusion assay. The regulatory mechanism
      between S042 and its targets was further investigated through Bioinformatics and
      qRT-PCR. This study served to highlight the role of the novel sRNA S042 in acid
      resistance of L. lactis and provided new insights into the response mechanism of
      acid stress.

PMID- 29654768
TI  - Seed-specific overexpression of AtFAX1 increases seed oil content in Arabidopsis.
AB  - Biosynthesis of plant seed oil is accomplished through the coordinate action of
      multiple enzymes in multiple subcellular compartments. Fatty acid (FA) has to be
      transported from plastid to endoplasmic reticulum (ER) for TAG synthesis.
      However, the role of plastid FA transportation during seed oil accumulation has
      not been evaluated. AtFAX1 (Arabidopsis fatty acid export1) mediated the FA
      export from plastid. In this study, we overexpressed AtFAX1 under the control of
      a seed specific promoter in Arabidopsis. The resultant overexpression lines (OEs)
      produced seeds which contained 21-33% more oil and 24-30% more protein per seed
      than those of the wild type (WT). The increased oil content was probably because
      of the enhanced FA and TAG synthetic activity. The seed size and weight were both
      increased accordingly. In addition, the seed number per silique and silique
      number per plant had no changes in transgenic plants. Taken together, our results
      demonstrated that seed specific overexpression of AtFAX1 could promote oil
      accumulation in Arabidopsis seeds and manipulating FA transportation is a
      feasible strategy for increasing the seed oil content.

PMID- 29654769
TI  - Apixaban attenuates ischemia-induced myocardial fibrosis by inhibition of Gq/PKC
      signaling.
AB  - It was previously found that patients with symptom of myocardial dysfunction had
      increased levels of thrombin. Apixaban is one of the novel oral anticoagulant
      drugs widely used in clinic. As the inhibitor of FXa (prothrombin), it inhibits
      prothrombin conversion into thrombin leading to thrombin deficiency in vivo.
      However, the effects of apixaban on myocardial fibrosis were still unclear, and
      the concomitant molecular mechanisms remain to be investigated. Here, we showed
      that myocardial fibrosis-bearing mice induced by continuous myocardial ischemia
      (MI) had higher levels of thrombin. Orally administration of apixaban
      significantly abrogated fibrosis condition and thrombin levels. In vitro,
      thrombin induced collagen deposition in primary cardiac fibroblasts in a dose
      dependent manner. Mechanistic experiments showed that thrombin induced collagen
      deposition by activation of the Par-1-coupled Gq/PKC signaling. Genetic ablation
      of Gq or pharmacological inhibition of PKC effectively blunted thrombin-induced
      collagen deposition in cardiac fibroblasts. Moreover, administration of PKC
      inhibitor or Gq antagonist obviously blocked MI-induced myocardial fibrosis in
      mice. To conclude, apixaban attenuates MI-induced myocardial fibrosis by
      inhibition of thrombin-dependent Par-1/Gq/PKC signaling axis.

PMID- 29654770
TI  - TRPV1-dependent ERK1/2 activation in porcine lens epithelium.
AB  - Recently we determined that the Transient Receptor Potential Vanilloid 4 ion
      channel (TRPV4) has a crucial signaling role in a pathway that regulates various
      aspects of lens epithelium function. Here, we report on a different TRPV channel,
      TRPV1, in porcine lens. The presence of TRPV1 in the lens was evident from RT-PCR
      studies and Western blot analysis of MAPK signaling pathway activation caused by
      the TRPV1 agonist capsaicin. TRPV1 mRNA was detected in the epithelium of porcine
      as well as human lens. Transient ERK1/2 and p38 MAPK phosphorylation was detected
      within 1 min in the epithelium isolated from intact porcine lenses exposed to
      capsaicin (100 nM), a selective TRPV1 agonist, and the response was significantly
      inhibited by A889245 (1.0 MUM), a TRPV1 antagonist. A similar ERK 1/2 and p38
      response in the epithelium, also inhibitable by A889245, was evident in lenses
      treated with hyperosmotic solution (350 vs 300 mOsm). Lenses pre-treated with
      either the cytosolic Ca2+ chelator BAPTA-AM or the PKC inhibitor sotrastaurin
      (1.0 MUM) had a diminished ERK1/2 activation response to capsaicin and
      hyperosmotic solution. Taken together the findings support the notion that TRPV1
      functions as a plasma membrane ion channel that, when activated, permits the
      entry of extracellular calcium into the lens epithelium, leading to activation of
      PKC, ERK1/2 and p38 MAPK. It is significant that the findings confirm earlier
      proposals that hyperosmotic stress is linked to TRPV1 channel activation in the
      mouse lens. Further studies are ongoing to determine what functional changes are
      triggered by the TRPV1-linked signaling pathways and how they might relate to
      lens volume homeostasis.

PMID- 29654771
TI  - Developmental analysis of SV2 in the embryonic chicken corneal epithelium.
AB  - Intraepithelial corneal nerves (ICNs) help protect the cornea as part of the
      blink reflex and by modulating tear production. ICNs are also thought to regulate
      the health and homeostasis of the cornea through the release of trophic factors.
      Disruption to these nerves can lead to vision loss. Despite their importance
      little is known about how corneal nerves function and even less is known about
      how the cornea is initially innervated during its embryonic development. Here, we
      investigated the innervation of the embryonic chicken cornea. Western blot and
      immunohistochemistry were used to characterize the localization of the synaptic
      vesicle marker SV2, a molecule thought to be involved in the release of trophic
      factors from sensory nerves. The data show that both SV2 and synaptotagmin co
      localize to ICNs. Nerves in the conjunctiva also contained SV2 and synaptotagmin,
      but these were localized to below the basal layers of the conjunctiva epithelium.
      SV2 isolated from corneal epithelium migrates in western blot at a heavier weight
      than SV2 isolated from brain, which suggests a role in vesicle targeting, as the
      deglycosylating enzyme PnGase does not affect corneal SV2.

PMID- 29654772
TI  - Mutations in KATNB1 Cause Complex Cerebral Malformations by Disrupting
      Asymmetrically Dividing Neural Progenitors.

PMID- 29654773
TI  - Procyanidin from peanut skin induces antiproliferative effect in human prostate
      carcinoma cells DU145.
AB  - In this study, the antiproliferative activity of peanut skin procyanidins (PSP)
      and six fractions (PSP-1~6) isolated from PSP by several chromatographic steps on
      the human prostate cancer DU145 cells were evaluated. The results showed that PSP
      and PSP-1~6 significantly inhibited the proliferation of DU145 cells. PSP-2 was
      the most effective fraction, which was identified as procyanidin B3 mainly and
      procyanidin dimer [(E)C-luteolin or keampferol] secondarily. Moreover, the
      mechanism of antiproliferative activity of PSP-2 was investigated. It was
      observed that PSP-2 induced apoptotic cell death and cell cycle arrest at S phase
      in DU145 cells. PSP-2 caused the increase of intracellular ROS level and the
      decrease of Bcl-2/Bax ratio, and triggered the activation of p53 and caspases-3
      in DU145 cells. Our findings demonstrated that procyanidins from peanut skin have
      the potential to be developed as an anti-prostate cancer agent.

PMID- 29654774
TI  - Volumetric Cleft Changes in Treatment With Bone Morphogenic Protein/beta
      Tricalcium Phosphate Versus Grafts From the Iliac Crest or Symphysis.
AB  - PURPOSE: To compare the volumetric changes in successfully treated clefts with
      secondary alveolar grafting using recombinant human bone morphogenic protein-2
      (rhBMP-2) delivered in beta-tricalcium phosphate (betaTCP) scaffold versus
      autogenous grafts obtained from the iliac crest and mandibular symphysis.
      PATIENTS AND METHODS: We performed a retrospective cohort study of cone-beam
      computed tomography scans of 25 subjects with unilateral or bilateral clefts. Of
      the 25 patients, 7 received an iliac crest bone graft, 9 received a mandibular
      symphyseal bone graft, and 9 subjects received the rhBMP-2/betaTCP bone
      substitute. Volumetric rendering software was used to calculate the amount of new
      bone formation and residual bone defect present in the cleft area. The data were
      analyzed using Wilcoxon and Kruskal-Wallis tests and Pearson's correlation
      coefficient. RESULTS: The mean percentage of new bone formation for the iliac
      crest, symphysis, and rhBMP-2/betaTCP was 85.47, 80.56, and 81.22%, respectively
      (P = .0854). The initial cleft volume had a weak positive correlation with the
      percentage of new bone formation (r = 0.18), but the postoperative residual cleft
      volume had a strong negative correlation (r = 0.71). CONCLUSIONS: rhBMP2
      delivered in a betaTCP scaffold in alveolar cleft patients can be a viable
      alternative to autogenous iliac crest and symphysis grafts, eliminating donor
      site morbidity.

PMID- 29654775
TI  - Correction of Delayed Traumatic Enophthalmos Using Customized Orbital Implants.
AB  - PURPOSE: To determine the relation between overcorrection of orbital volume and
      ocular projection in patients with orbital trauma. MATERIALS AND METHODS: A
      prospective cohort study was performed of patients with enophthalmos as a side
      effect of orbital trauma. The sample included patients older than 18 years who
      required reconstruction using customized implants to treat enophthalmos with or
      without diplopia. The exclusion criteria were patients who had multiple or
      extended fractures and patients with amaurosis or a prosthetic eye. Orbital
      volumes were calculated and the position of the eyeball in the healthy and
      traumatized sockets was determined before and after installing the implant and
      the ratio between these variables was calculated. Two variables were identified:
      1) orbital volume and 2) enophthalmos. Analysis of the estimator variables was
      performed, defining 3 groups: 1) healthy eye socket, 2) traumatized eye socket
      without implant, and 3) traumatized eye socket with implant. The Shapiro-Wilk
      test, paired t test, and linear regression analysis were performed. A P value
      less than .05 (95% confidence interval) indicated significant differences.
      RESULTS: Of 294 patients who underwent orbital zygomatic complex reconstruction
      surgery, 13 required customized implants and only 5 met the inclusion criteria.
      The average volumetric variation in the groups of traumatized eye sockets with
      and without implants was statistically significant (P < .05), overcorrecting by
      an average of 4.2 cm3. The average enophthalmos variation in the groups of
      traumatized eye sockets with and without implants was statistically significant
      (P < .05), projecting the eyeball by an average 1.80 mm. The ratio between the
      average orbital volume and projection of the eyeball was determined to be 1:0.721
      (correlation, 45.6%). CONCLUSION: This study concluded that the eyeball is
      projected 0.7 mm for every 1 cm3 of volume added in customized orbital implants.
      However, additional clinical studies with larger samples should be conducted.

PMID- 29654776
TI  - Hypertrophic Mental Tubercles of the Mandible.
AB  - PURPOSE: Enlarged mental tubercles are rare benign exostoses that occur in
      children. The purpose of this study was to report a case series of patients with
      hypertrophic mental tubercles and propose a theory for their etiopathogenesis.
      PATIENTS AND METHODS: In this retrospective case series of patients with
      hypertrophic mental tubercles, we reviewed patients' medical records for age,
      gender, clinical presentation, findings on physical examination and radiographic
      images, and management details. Descriptive data were summarized. RESULTS: The
      sample included 14 patients (71% of whom were male patients) who presented at a
      mean age of 12.9 +/- 4.8 years (range, 6 to 21 years). Most patients had
      bilaterally enlarged mental tubercles (n = 8); unilateral cases were primarily on
      the left side (5 of 6 patients). On clinical examination, a bony prominence in
      the parasymphyseal region was noted on palpation and occasionally by visual
      inspection. No tenderness to palpation or overlying skin changes were noted.
      Typical radiographic features included asymmetry along the inferior border of the
      mandible in the parasymphyseal region on panoramic radiographs and prominence
      and/or enlargement of the mental tubercles on computed tomography scans. No
      evidence of cortical expansion, perforation, or periosteal reaction was found.
      Three patients requested contouring of the hypertrophied tubercles. CONCLUSIONS:
      Hypertrophic mental tubercles are rare bony exostoses that occur in children in a
      region where a confluence of facial muscles attach to the mandible. The etiology
      likely involves bone deposition occurring in an area of muscle pull.

PMID- 29654777
TI  - Evaluation of Andrews' Analysis as a Predictor of Ideal Sagittal Maxillary
      Positioning in Orthognathic Surgery.
AB  - PURPOSE: There is no universally accepted method for determining the ideal
      sagittal position of the maxilla in orthognathic surgery. In "Element II" of "The
      Six Elements of Orofacial Harmony," Andrews used the forehead to define the goal
      maxillary position. The purpose of this study was to compare how well this
      analysis correlated with postoperative findings in patients who underwent
      bimaxillary orthognathic surgery planned using other guidelines. The authors
      hypothesized that the Andrews analysis would more consistently reflect clinical
      outcomes than standard angular and linear measurements. MATERIALS AND METHODS:
      This is a retrospective cohort study of patients who had bimaxillary orthognathic
      surgery and achieved an acceptable esthetic outcome. Patients with no maxillary
      sagittal movement, obstructive sleep apnea, cleft or craniofacial diagnoses, or
      who were non-Caucasian were excluded. Treatment plans were developed using
      photographs, radiographs, and standard cephalometric measurements. The Andrews
      analysis, measuring the distance from the maxillary incisor to the goal anterior
      limit line, and standard measurements were applied to end-treatment records. The
      Andrews analysis was statistically compared with standard methods. RESULTS: There
      were 493 patients who had orthognathic surgery from 2007 through 2014, and 60
      (62% women; mean age, 22.1 +/- 6.8 yr) met the criteria for inclusion in this
      study. The mean Andrews distances were -4.8 +/- 2.9 mm for women and -8.6 +/- 4.6
      mm for men preoperatively and -0.6 +/- 2.1 mm for women and -1.9 +/- 3.4 mm for
      men postoperatively. For women, the Andrews analysis was closer to the goal value
      (0 mm) postoperatively than any standard measurement (P < .001). For men, the
      linear distance from the A point to a vertical line tangent to the nasion from
      the McNamara analysis performed best (P < .001), followed by the Andrews
      analysis. CONCLUSION: The Andrews analysis correlated well with the final
      esthetic sagittal maxillary position in the present sample, particularly for
      women, and could be a useful tool for orthognathic surgical planning.

PMID- 29654778
TI  - Can Hyaluronidase Be an Alternative Postoperative Anti-edema Agent to
      Dexamethasone? Preliminary Results of an Animal Study.
AB  - PURPOSE: Recombinant human hyaluronidase (rHuPH20) is widely used as a spreading
      factor, which enhances the absorption of subcutaneously injected medicines. The
      anti-inflammatory and anti-edema effects of the enzyme were demonstrated in
      previous studies. In the present study, the anti-edema effect of rHuPH20 was
      compared with that of dexamethasone in a traumatic rat paw edema model. MATERIALS
      AND METHODS: Twenty-four Sprague-Dawley rats (weight 200 to 450 g) were divided
      into 3 groups: control (group 1), rHuPH20 (group 2), and dexamethasone (group 3).
      Traumatic edema was induced in the right hind paws of the rats using Feeney's
      weight-drop model. After edema induction, 0.4 mL of rHuPH20 (100 U/kg = 0.88
      MUg/kg dose) and 0.4 mL of dexamethasone (0.5 mg/kg dose) were injected into the
      right hind paws of the rats in groups 2 and 3. The paw volumes were measured
      before edema induction and at 3, 6, 12, 24, 48, and 72 hours after induction
      using a plethysmometer. The Mann-Whitney U test was used for the statistical
      analyses. Probabilities < .05 were accepted as statistically significant.
      RESULTS: The between percentage change in the edema mean values of groups 1 and 3
      showed no significant difference at all time points; however, group 2 showed
      significantly less change in the edema mean values at 3, 6, 12, 24, and 48 hours
      after edema induction (P < .05) compared with group 1. The change in the edema
      mean value for group 2 was significantly less than that for group 3 at 3, 6, 12,
      24, and 48 hours after edema induction (P < .05). CONCLUSIONS: Local rHuPH20
      injection more effectively reduced the edema that was induced traumatically in
      rat paws than did dexamethasone. However, further clinical studies are needed
      regarding the use of rHuPH20 as a postoperative anti-edema agent in place of
      dexamethasone.

PMID- 29654779
TI  - Height Changes of Tutoplast-Processed Fascia Lata Over Time After Dorsal
      Augmentation During Rhinoplasty.
AB  - PURPOSE: Tutoplast (Tutogen Medical, Neunkirchen am Brand, Germany)-processed
      fascia lata (TPFL) has been used for dorsal augmentation in rhinoplasty in the
      Republic of Korea for approximately 10 years, but few studies have described
      changes in TPFL in terms of dorsal height over time. We investigated changes in
      dorsal height after TPFL use as a dorsal implant material during rhinoplasty.
      MATERIALS AND METHODS: The records of 18 rhinoplasty patients who had undergone
      dorsal augmentation with TPFL were examined retrospectively. The patients had
      undergone rhinoplasty from March 2008 to June 2012. Two different ear, nose, and
      throat doctors analyzed the first follow-up photographs (2 lateral views and 2
      oblique views) taken at approximately 1 month postoperatively and the last follow
      up photographs taken from 18 to 75 months after surgery. The last follow-up
      photographs were classified as showing no nasal dorsal height change, slight
      change, and marked change compared with the first follow-up photographs. RESULTS:
      Of the 18 patients enrolled, 50% (n = 9) showed no change in the nasal dorsum
      whereas 33% (n = 6) showed mild depression and 17% (n = 3) showed marked
      depression of the nasal dorsum at last follow-up. CONCLUSIONS: About half of the
      patients who had undergone dorsal augmentation using TPFL during rhinoplasty
      showed mild or marked dorsal depression over time. It is recommended that TPFL be
      used with another implant during augmentation rhinoplasty or TPFL be used only
      for a slightly depressed nose. In addition, patients should be informed that TPFL
      could be resorbed over time.

PMID- 29654780
TI  - Knotless Suture for Wound Closure in Intraoral Surgery-A Report of 2 Cases.
AB  - Suturing is the most commonly used method of wound closure in intraoral surgery,
      whose objectives include anatomic reapproximation of tissues, hemostasis, and
      prevention of wound contamination by providing an adequate tissue seal.
      Conventional suturing in the oral cavity is difficult because of the restricted
      space for instrumentation. Further, knots act as a nidus to food entrapment and
      microbial colonization. The knotless (barbed) suture could be considered an ideal
      alternative to eliminate these limitations. This report describes the
      effectiveness of the intraoral use of the knotless suture after open reduction
      and internal fixation of maxillofacial fractures.

PMID- 29654781
TI  - Effects of propofol on cancer development and chemotherapy: Potential mechanisms.
AB  - Propofol (2, 6-diisopropylphenol) is the commonly used intravenous sedative
      hypnotic agent. Accumulating evidence shows that propofol affects cancer
      development by direct and indirect ways. In this review, we will provide an
      overview of the effects of propofol on cancer development and chemotherapy, with
      a special focus on the underlying molecular mechanisms involved. Propofol
      regulates both microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), and serves
      as a regulator of different signaling pathways including hypoxia-inducible factor
      1alpha (HIF-1alpha), mitogen-activated protein kinase (MAPK), nuclear factor
      kappaB (NF-kappaB), and nuclear factor E2-related factor-2 (Nrf2) pathways. In
      addition, propofol modulates host immune function. Possible correlation between
      propofol and cancer should be verified in further studies, including animal
      trials and prospective clinical studies.

PMID- 29654782
TI  - Mirabegron, a beta3-adrenoceptor agonist reduced platelet aggregation through
      cyclic adenosine monophosphate accumulation.
AB  - Mirabegron is a beta3-adrenoceptor agonist and released on the marked for the
      treatment of overactive bladder. Because mirabegron is the only beta3
      adrenoceptor agonist available and substances that increase the levels of cyclic
      adenosine monophosphate (cAMP) inhibit platelet activity, we tested the
      hypothesis that mirabegron could have antiplatelet activity. Collagen- and
      thrombin induced platelet aggregation, thromboxane B2 (TXB2) and cyclic
      nucleotides quantification and calcium (Ca2+) mobilization were determined in the
      absence and presence of mirabegron in human washed platelets. Our results
      revealed that mirabegron (10-300 uM) produced significant inhibitions on platelet
      aggregation induced by collagen- or thrombin, accompanied by greater
      intracellular levels of cAMP. The beta3-adrenoceptor antagonist L 748,337 (1 uM)
      and the adenylate cyclase inhibitor, SQ 22,536 (100 uM) reversed the inhibition
      induced by mirabegron in thrombin-stimulated platelets. The selective antagonists
      for beta1-and beta2-adrenoceptors, atenolol and ICI 117,551 (3 uM), respectively
      did not interfere on the inhibition induced by mirabegron. In Fluo-4 loaded
      platelets, mirabegron reduced the total and intracellular Ca2+ levels. Pre
      incubation with mirabegron almost abolished the levels of TXB2. Mirabegron did
      not augment the intracellular levels of cyclic guanosine monophosphate. In
      conclusion, mirabegron inhibited human platelet aggregation through cAMP
      accumulation, thus suggesting that substances that activate beta3-adrenoceptor
      could be beneficial as adjuvant antiplatelet therapy.

PMID- 29654783
TI  - Resveratrol attenuates pro-inflammatory cytokines and activation of JAK1-STAT3 in
      BTBR T+ Itpr3tf/J autistic mice.
AB  - Autism is a neurodevelopmental disorder characterized by qualitative impairment
      in communication, social interaction, and repetitive stereotypic behavior.
      Resveratrol plays a role in several disorders such as neuroimmune, autoimmune,
      and allergic disorders. BTBR T+ Itpr3tf/J (BTBR) mice, a model for autism, show
      several behavioral deficits that are physiological characteristics similar to
      those observed in patients with autism. Previous studies have shown that JAK-STAT
      signaling pathway is associated with many neurodevelopmental disorders. We
      investigated the possible role of resveratrol on IL-6+, TNF-alpha+, IFN-gamma+,
      and STAT3+ in CD4+ T spleen cells in BTBR mice as compared to C57BL/6J mice. We
      also assessed the effect of resveratrol treatment on IL-6, TNF-alpha, IFN-gamma,
      JAK1, and STAT3 mRNA expression levels in the brain tissue. We further assessed
      IL-6, IFN-gamma, TNF-alpha, phosphorylated (p) JAK1, and pSTAT3 (Tyr705) protein
      expression levels in the brain tissue. Resveratrol (20 and 40 mg/kg)-treated mice
      had significantly decreased in IL-6+, TNF-alpha+, IFN-gamma+, and STAT3+ in CD4+
      spleen cells as compared with BTBR control mice. Resveratrol treatment also
      decreased IL-6, TNF-alpha, IFN-gamma, JAK1, and STAT3 mRNA expression levels as
      compared with BTBR control mice in the brain tissue. Moreover, resveratrol
      treatment resulted in decreased protein expression levels of IL-6, IFN-gamma, TNF
      alpha, pJAK1, and pSTAT3 (Tyr705) as compared with BTBR control mice in the brain
      tissues. Taken together, these results indicate the efficacy of resveratrol in
      reducing cytokines and JAK-1/STAT3 signaling in BTBR mice, which is a novel and
      important finding and might be important for future therapies in neuroimmune
      dysfunction.

PMID- 29654784
TI  - The Mechanisms of PML-Nuclear Body Formation.

PMID- 29654785
TI  - A metabolomics study on the immunosuppressive effect of Tripterygium hypoglaucum
      (Levl.) Hutch in mice: The discovery of pathway differences in serum metabolites.
AB  - Tripterygium hypoglaucum (Levl.) Hutch (THH), a typical traditional Chinese
      medicine, is widely used in clinical practice for the treatment of rheumatoid
      arthritis, systemic lupus erythematous, and other connective tissue and
      autoimmune diseases. However, most related researches focused on the
      pharmacological effects of THH, while less attention has been paid to the
      immunosuppressive mechanism. The present study aims to determine the metabolic
      profiles, based on UPLC-Q-TOF-MS, identify differential metabolites, and find
      related metabolic pathways among the sensitization red blood cell (SRBC) model
      mice, THH treated mice, and cyclophosphamide treated group. Totally, 24 and 19
      changed metabolites were found in the THH and cyclophosphamide treated groups
      respectively. Among them, we found that urocanate metabolic pathway change could
      be considered as the most relevant pathway associated with immunosuppression.
      This is the first study that comprehensively assessed the differences in
      metabolome between the model and THH treated groups. The results provide insights
      into the difference between the immunosuppressive mechanisms of THH and
      cyclophosphamide and also demonstrated that metabolomics is a valuable tool for
      investigating the efficacy of drugs in the treatment of diseases and the
      associated mechanism involved.

PMID- 29654786
TI  - Biochemical and molecular analyses of infantile sialic acid storage disease in a
      patient with nonimmune hydrops fetalis.
AB  - Nonimmune hydrops fetalis is the most severe clinical manifestation of lysosomal
      storage diseases (LSDs). Around 14 different LSDs have been accounted for as 1
      15% of the cause of nonimmune hydrops fetalis. We report a Korean infant affected
      by an extremely rare but severe form of sialic acid storage disease. The patient
      presented with nonimmune hydrops fetalis, dysmorphic facial features,
      hepatosplenomegaly, and dysostosis multiplex and died at 39 days of age due to
      persistent pulmonary hypertension. LSD was suspected based on the presence of
      diffuse vacuolation of syncytiotrophoblast, villous stromal cells, and
      intermediate trophoblast in placental biopsy. Increased excretion of urinary free
      sialic acid was detected by liquid chromatography-tandem mass spectrometry. The
      patient was compound heterozygous of the c.908G>A (p.Trp303Ter) and the splicing
      mutation c.1259+5G>T (IVS9+5 G>T) in the SLC17A5 gene.

PMID- 29654788
TI  - ERP evidence for implicit L2 word stress knowledge in listeners of a fixed-stress
      language.
AB  - Languages with contrastive stress, such as English or German, distinguish some
      words only via the stress status of their syllables, such as "CONtent" and
      "conTENT" (capitals indicate a stressed syllable). Listeners with a fixed-stress
      native language, such as Hungarian, have difficulties in explicitly
      discriminating variation of the stress position in a second language (L2).
      However, Event-Related Potentials (ERPs) indicate that Hungarian listeners
      implicitly notice variation from their native fixed-stress pattern. Here we used
      ERPs to investigate Hungarian listeners' implicit L2 processing. In a cross-modal
      word fragment priming experiment, we presented spoken stressed and unstressed
      German word onsets (primes) followed by printed versions of initially stressed
      and initially unstressed German words (targets). ERPs reflected stress priming
      exerted by both prime types. This indicates that Hungarian listeners implicitly
      linked German words with the stress status of the primes. Thus, the formerly
      described explicit stress discrimination difficulty associated with a fixed
      stress native language does not generalize to implicit aspects of L2 word stress
      processing.

PMID- 29654787
TI  - Prognostic role of microRNA-155 in patients with leukemia: A meta-analysis.
AB  - BACKGROUND: Recent studies have shown that microRNA-155 (miR-155) is correlated
      with clinical outcomes of leukemia. This meta-analysis explores to evaluate the
      prognostic value of miR-155 for survival in patients with leukemia. METHODS:
      Eligible studies were searched from PubMed and EMBASE databases. Hazard ratios
      (HRs) and corresponding 95% confidence intervals (CIs) for overall survival (OS),
      disease-free survival, event-free survival, progression-free survival and
      treatment-free survival were extracted, if available. Pooled HRs and 95% CIs were
      used to study any correlation between miR-155 and survival. RESULTS: 11 studies
      from 10 articles containing 1718 leukemia patients were included. Data showed
      that the pooled HR for OS was 1.67 (95% CI: 1.44-1.95, P < 0.01). Subgroup
      analyses for OS showed that the pooled HRs and their 95% CIs were 1.68, 1.41-2.00
      (P < 0.01) and 1.73, 1.25-2.41 (P < 0.01) for acute myeloid leukemia and chronic
      lymphoblastic leukemia, respectively. Furthermore, there was no significant
      heterogeneity or publication bias among the enrolled datasets. CONCLUSION: We
      conclude that high miR-155 expression was associated with shorter OS for leukemia
      patients, and that miR-155 might be a promising prognostic biomarker for this
      patient population.

PMID- 29654789
TI  - Detection of four regulated grapevine viruses in a qualitative, single tube real
      time PCR with melting curve analysis.
AB  - The detection of the four grapevine viruses (GLRaV-1, GLRaV-3, GFLV and ArMV)
      regulated in European Union plant material certification, requires sensitive and
      specific diagnostic tools. A strategy of simultaneous detection in a real-time
      single tube amplification was developed, based on the EvaGreen binding dye. The
      melting curve analysis (MCA) of the amplicons allows a qualitative detection of
      the four different virus targets in multiplex analysis. A plasmid dilution assay
      calculated an analytical sensitivity with an amplification threshold up to 100
      copies of the target sequences. A small cohort of field grapevine samples, with a
      known status of infection by mixtures of the target viruses or free of them,
      respectively, was successfully tested for the evaluation of the amplicons Tm.

PMID- 29654790
TI  - Scarless wound healing: From development to senescence.
AB  - An essential element of tissue homeostasis is the response to injuries, cutaneous
      wound healing being the most studied example. In the adults, wound healing aims
      at quickly restoring the barrier function of the skin, leading however to scar, a
      dysfunctional fibrotic tissue. On the other hand, in fetuses a scarless tissue
      regeneration takes place. During ageing, the wound healing capacity declines;
      however, in the absence of comorbidities a higher quality in tissue repair is
      observed. Senescent cells have been found to accumulate in chronic unhealed
      wounds, but more recent reports indicate that their transient presence may be
      beneficial for tissue repair. In this review data on skin wound healing and
      scarring are presented, covering the whole spectrum from early embryonic
      development to adulthood, and furthermore until ageing of the organism.

PMID- 29654791
TI  - Modelling mass diffusion for a multi-layer sphere immersed in a semi-infinite
      medium: application to drug delivery.
AB  - We present a general mechanistic model of mass diffusion for a composite sphere
      placed in a large ambient medium. The multi-layer problem is described by a
      system of diffusion equations coupled via interlayer boundary conditions such as
      those imposing a finite mass resistance at the external surface of the sphere.
      While the work is applicable to the generic problem of heat or mass transfer in a
      multi-layer sphere, the analysis and results are presented in the context of drug
      kinetics for desorbing and absorbing spherical microcapsules. We derive an
      analytical solution for the concentration in the sphere and in the surrounding
      medium that avoids any artificial truncation at a finite distance. The closed
      form solution in each concentric layer is expressed in terms of a suitably
      defined inverse Laplace transform that can be evaluated numerically.
      Concentration profiles and drug mass curves in the spherical layers and in the
      external environment are presented and the dependency of the solution on the mass
      transfer coefficient at the surface of the sphere analyzed.

PMID- 29654792
TI  - Who is the infector? Epidemic models with symptomatic and asymptomatic cases.
AB  - What role do asymptomatically infected individuals play in the transmission
      dynamics? There are many diseases, such as norovirus and influenza, where some
      infected hosts show symptoms of the disease while others are asymptomatically
      infected, i.e. do not show any symptoms. The current paper considers a class of
      epidemic models following an SEIR (Susceptible  ->  Exposed  ->  Infectious  -> 
      Recovered) structure that allows for both symptomatic and asymptomatic cases. The
      following question is addressed: what fraction rho of those individuals getting
      infected are infected by symptomatic (asymptomatic) cases? This is a more
      complicated question than the related question for the beginning of the epidemic:
      what fraction of the expected number of secondary cases of a typical newly
      infected individual, i.e. what fraction of the basic reproduction number R0, is
      caused by symptomatic individuals? The latter fraction only depends on the type
      specific reproduction numbers, while the former fraction rho also depends on
      timing and hence on the probabilistic distributions of latent and infectious
      periods of the two types (not only their means). Bounds on rho are derived for
      the situation where these distributions (and even their means) are unknown.
      Special attention is given to the class of Markov models and the class of
      continuous-time Reed-Frost models as two classes of distribution functions for
      latent and infectious periods. We show how these two classes of models can
      exhibit very different behaviour.

PMID- 29654793
TI  - Immune signatures associated with mortality differ in elderly populations from
      different birth cohorts and countries even within northern Europe.
AB  - Since associations between lifespan and certain simple immune parameters such as
      T cell proliferative responses to mitogens were reported in the 1970's, efforts
      to dissect out immune parameters correlating with morbidity and mortality have
      sought to define factors predicting individual longevity. Such "immune
      signatures" associating with defined clinical outcomes would represent biomarkers
      of "immunosenescence" that might also provide mechanistic insights into the
      ageing process. Because appropriate immune function is necessary for a healthy
      old age, a better understanding of immunosenescence contributing to frailty and
      death might allow interventions to improve personal and public health. Here, we
      discuss data from our studies in several different European countries and
      document significant differences between overtly similar populations. These
      findings draw attention to the marked variation even between presumably quite
      homogeneous populations, which may be due to the different birth cohorts studied
      in addition to numerous other variables. Thus, immunological parameters, and
      presumably many other factors, are sensitive to context-dependent variation,
      making it currently difficult to extrapolate biomarkers of longevity from any one
      human population to another.

PMID- 29654794
TI  - Piracetam attenuates binge eating disorder related symptoms in rats.
AB  - Binge eating disorder (BED) is a stress-related disorder characterized by acute
      episodes of excessive food intake. Piracetam, a nootropic agent has been reported
      to show several other neuropharmacological properties. The present study,
      evaluated the pharmacological effect of piracetam (200 mg/kg i.p.) on BED in
      female rats, induced by free access to palatable cookies for 2 h on alternate
      days. BED was confirmed by an increase in binge eating behavior and weight gain.
      BED leads to anxiety, cognitive and memory deficits, as evaluated by EPM
      (Elevated plus maze), OFT (open field test), and Y-maze tests. Increased levels
      of plasma corticosterone (CORT), glutamate in nucleus accumbens (NAC),
      hypothalamus (HYP) and prefrontal cortex (PFC) indicate stress and
      excitotoxicity. Moreover, it was observed that the levels of dopamine were higher
      in NAC and PFC, and less in HYP which may be responsible for motivational
      behavior for palatable feeding and cognitive deficits. More surprisingly, feeding
      behaviour regulating hormones namelyleptin was increased and ghrelin level was
      decreased in BED. Further, level of acetylcholine which regulates cognitive
      behaviour was compromised in BED. Piracetam significantly decreased binge eating
      behavior and associated body weight and regulated the levels of concerned
      neurotransmitters in respective regions. However, piracetam did not alter normal
      feeding behavior in the fast-refed model. Further, piracetam showed brain region
      specific decrease in vascular endothelial growth factor expression. Piracetam
      showed anxiolytic activity and also alleviated cognitive deficit observed in BED.
      Hence, preclinical evidence indicates the potential use of piracetam for the
      treatment of BED.

PMID- 29654795
TI  - Promiscuous and Selective: How Intrinsically Disordered BH3 Proteins Interact
      with Their Pro-survival Partner MCL-1.
AB  - The BCL-2 family of proteins plays a central role in regulating cell survival and
      apoptosis. Disordered BH3-only proteins bind promiscuously to a number of
      different BCL-2 proteins, with binding affinities that vary by orders of
      magnitude. Here we investigate the basis for these differences in affinity. We
      show that eight different disordered BH3 proteins all bind to their BCL-2 partner
      (MCL-1) very rapidly, and that the differences in sequences result in different
      dissociation rates. Similarly, mutation of the binding surface of MCL-1 generally
      affects association kinetics in the same way for all BH3 peptides but has
      significantly different effects on the dissociation rates. Importantly, we infer
      that the evolution of homologous, competing interacting partners has resulted in
      complexes with significantly different lifetimes.

PMID- 29654796
TI  - Combinatorial Design of a Nanobody that Specifically Targets Structured RNAs.
AB  - Recent advances in transcriptome sequencing and analysis have revealed the
      complexity of the human genome. The majority (~ 98%) of cellular transcripts is
      not translated into proteins and represents a vast, unchartered world of
      functional non-coding RNAs. Most of them adopt a well-defined three-dimensional
      structure to achieve their biological functions. However, only very few RNA
      structures are currently available which reflects the challenges associated with
      RNA crystallization. Nevertheless, these structures would represent a critical
      step in understanding functions of non-coding RNAs and their molecular mechanisms
      in the cell. The overall goal of this study is to develop an innovative and
      versatile tool to facilitate the functional study and crystallization of
      structured RNAs (stRNAs). In this work, we have engineered an antibody fragment
      from camelid heavy-chain antibody (nanobody) able to specifically bind with low
      nanomolar affinity to stRNA, while no binding could be detected for single
      stranded DNA/RNA, double-stranded DNA/RNA or a negatively charged protein.
      However, this nanobody recognizes different and non-related stRNAs, this
      observation suggests that it binds to an epitope shared by these stRNAs. Finally,
      our data also show that the binding of the nanobody does not alter the secondary
      structure content of the stRNA as well as its unfolding/refolding processes
      during heat treatment. This work constitutes a successful proof of concept
      demonstrating that nanobodies can be engineered to recognize RNA-related
      epitopes.

PMID- 29654797
TI  - Efficacy of paclitaxel/dexamethasone intra-tumoral delivery in treating
      orthotopic mouse breast cancer.
AB  - The effect of topical co-administration of promoter drugs with paclitaxel to
      increase anti-tumor effects of paclitaxel was investigated. Mice with orthotopic
      4T1-Luc breast cancer received single intra-tumoral injection of a polymeric
      formulation with paclitaxel and a specific promoter drug. Several promoter drugs
      were evaluated, including: dexamethasone, losartan, nicotinamide, Azone, and
      oleic acid. Dexamethasone exhibited the highest effect on paclitaxel anti-tumor
      activity, in a dose-dependent fashion. However, this effect was accompanied by
      systemic effects of dexamethasone, and inability to prevent tumor metastasis to
      the lungs. Topical co-administration of promoter drugs with anti-cancer agents
      can enhance their anti-tumor effects. Further investigations are needed to
      identify the most efficient combinations of promoter and anti-cancer drugs, and
      their suitability for the clinical management of the breast cancer disease.

PMID- 29654798
TI  - Tailoring supersaturation from amorphous solid dispersions.
AB  - The maximum achievable concentration of a drug in solution is dictated by the
      chemical potential of the solid form. Because an amorphous solid has a higher
      chemical potential than the corresponding crystal form, in the absence of phase
      transformations, a higher transient solubility is expected. However, the chemical
      potential of an amorphous drug can be reduced by mixing with another component.
      Therefore, upon mixing with a polymer to form an amorphous solid dispersion
      (ASD), the maximum solution concentration achieved can be potentially altered, in
      particular if the polymer is poorly soluble in the dissolution medium. Such
      changes in the chemical potential of the drug may be a critical factor in
      determining the maximum achievable solution concentration, and could alter the
      crystallization driving force of the drug. Therefore, the aim of this study was
      to gain insights into the impact of poorly soluble polymers on the "amorphous
      solubility" of drugs formulated as amorphous solid dispersions. Lopinavir was
      selected as a model drug with a low crystallization tendency, enabling
      determination of the amorphous solubility as a function of ASD composition. Model
      polymers included cellulose acetate (CA), CA phthalate (CAP), ethylcellulose
      (EC), Eudragit(r) RL PO (EUD), hydroxypropylmethylcellulose (HPMC), HPMC acetate
      succinate (HPMCAS), and HPMC phthalate (HPMCP). The "amorphous solubility" of the
      drug alone was determined and then the changes in maximum achievable
      concentration were measured as a function of drug loading. Drug-polymer
      interactions were characterized using infrared spectroscopy (IR), differential
      scanning calorimetry (DSC) and moisture sorption analysis. The results showed
      that the maximum achievable concentration ("amorphous solubility") of lopinavir
      varied with the extent of drug-polymer interactions, as well as the drug weight
      fraction in the ASD. This information is of great value when evaluating the
      maximum achievable concentration of amorphous systems formulated with pH
      responsive polymers, and should contribute to a broader understanding of drug
      phase behavior in the context of ASDs.

PMID- 29654799
TI  - Immobilization of microalgae on the surface of new cross-linked polyethylenimine
      based sorbents.
AB  - We report on the use of the polyethylenimine-based (PEI) sorbents for
      immobilization and harvesting of microalgae (MA) cells. Specific materials
      assessed were porous solid polymers from highly-branched PEI synthesized by cross
      linking with epichlorohydrin (ECH) or diethylene glycol diglycidyl ether (DGDE).
      We estimated the effect of PEI/cross-linker ratio on the MA attachment and
      biocompatibility of the sorbents with the MA cells. A decrease in the cross
      linker percentage resulted in the enhancement of the immobilization efficiency
      but impaired the cell viability as was manifested by inhibition of the
      photosynthetic activity of the MA cells. The rate of Chlorella vulgaris cell
      attachment to the sorbents with ECH was faster as compared to that of the PEI
      DGDE-based polymers. The cells immobilized on the PEI-ECH sorbents showed a more
      profound decline in their viability (assessed via photosynthetic activity). The
      sorbents with 60% of DGDE were characterized by high immobilization efficiency.
      These sorbents supported a prolonged cultivation of the immobilized MA without
      impairing their viability and metabolic activity. We conclude that the sorbents
      with a lower percentage of DGDE (<30%) and sorbents with ECH are suitable for
      harvesting of the MA cells intended for immediate downstream processing,
      potentially without the cell desorption. To the best of our knowledge, this is
      the first report on successful application of PEI-based sorbents in microalgal
      biotechnology.

PMID- 29654800
TI  - The evolution of subtype B HIV-1 tat in the Netherlands during 1985-2012.
AB  - For the production of viral genomic RNA, HIV-1 is dependent on an early viral
      protein, Tat, which is required for high-level transcription. The quantity of
      viral RNA detectable in blood of HIV-1 infected individuals varies dramatically,
      and a factor involved could be the efficiency of Tat protein variants to
      stimulate RNA transcription. HIV-1 virulence, measured by set-point viral load,
      has been observed to increase over time in the Netherlands and elsewhere.
      Investigation of tat gene evolution in clinical isolates could discover a role of
      Tat in this changing virulence. A dataset of 291 Dutch HIV-1 subtype B tat genes,
      derived from full-length HIV-1 genome sequences from samples obtained between
      1985-2012, was used to analyse the evolution of Tat. Twenty-two patient-derived
      tat genes, and the control TatHXB2 were analysed for their capacity to stimulate
      expression of an LTR-luciferase reporter gene construct in diverse cell lines, as
      well as for their ability to complement a tat-defective HIV-1LAI clone. Analysis
      of 291 historical tat sequences from the Netherlands showed ample amino acid (aa)
      variation between isolates, although no specific mutations were selected for over
      time. Of note, however, the encoded protein varied its length over the years
      through the loss or gain of stop codons in the second exon. In transmission
      clusters, a selection against the shorter Tat86 ORF was apparent in favour of the
      more common Tat101 version, likely due to negative selection against Tat86
      itself, although random drift, transmission bottlenecks, or linkage to other
      variants could also explain the observation. There was no correlation between Tat
      length and set-point viral load; however, the number of non-intermediate variants
      in our study was small. In addition, variation in the length of Tat did not
      significantly change its capacity to stimulate transcription. From 1985 till
      2012, variation in the length of the HIV-1 subtype B tat gene is increasingly
      found in the Dutch epidemic. However, as Tat proteins did not differ
      significantly in their capacity to stimulate transcription elongation in vitro,
      the increased HIV-1 virulence seen in recent years could not be linked to an
      evolving viral Tat protein.

PMID- 29654801
TI  - Liver X receptor beta in the hippocampus: A potential novel target for the
      treatment of major depressive disorder?
AB  - Liver X receptors (LXRs), including LXRalpha and LXRbeta isoforms, have been
      implicated in multiple physiological functions including promoting neurogenesis,
      improving synaptic plasticity, preventing neurodegeneration, inhibiting
      inflammation as well as regulating cholesterol metabolism. However, a potential
      role of LXRs in the treatment of major depressive disorder (MDD) has never been
      investigated previously. Our present results demonstrated that levels of
      hippocampal LXRbeta but not LXRalpha were down-regulated in rats exposed to
      chronic unpredictable stress (CUS) and were negatively correlated with the
      severity of CUS-induced depressive-like behaviors. Furthermore, rats with LXRbeta
      knockdown by short hairpin RNA (shRNA) in hippocampus displayed depressive-like
      behaviors and impaired hippocampal neurogenesis similar to those observed after
      CUS exposure. Conversely, LXRs activation by GW3965 (GW), a synthetic dual
      agonist for both LXRalpha and LXRbeta isoforms, could improve depression-like
      behaviors and reverse the impaired hippocampal neurogenesis in rats exposed to
      CUS. LXRbeta knockdown by shRNA completely abrogated the antidepressant and
      hippocampal neurogenesis-promoting effects of GW, suggesting that LXRbeta isoform
      mediated the antidepressant and hippocampal neurogenesis-promoting effects of the
      LXRalpha/beta dual agonist. However, ablation of hippocampal neurogenesis with x
      irradiation only partly but not completely abolished the antidepressant effects
      of GW in the behavioral tests, implying that the antidepressant effects mediated
      by LXRbeta isoform are likely through both neurogenesis-dependent and 
      independent pathways. Thus, our findings suggest that LXRbeta activation may
      represent a potential novel target for the treatment of MDD and also provide a
      novel insight into the underlying mechanisms of MDD.

PMID- 29654802
TI  - Saving lives with public access defibrillation: A deadly game of hide and seek.
AB  - BACKGROUND: Early defibrillation is a critical link in the chain of survival.
      Public access defibrillation (PAD) programmes utilising automated external
      defibrillators (AEDs) aim to decrease the time-to-first-shock, and improve
      survival from out-of-hospital cardiac arrest. Effective use of PADs requires
      rapid location of the device, facilitated by adequate signage. We aimed to
      therefore assess the quality of signage for PADs in the community. METHOD: From
      April 2017 to January 2018 we surveyed community PADs available for public use on
      the 'Save a Life' AED locator mobile application in and around Southampton, UK.
      Location and signage characteristics were collected, and the distance from the
      furthest sign to the AED was measured. RESULTS: Researchers evaluated 201
      separate PADs. All devices visited were included in the final analysis. No
      signage at all was present for 135 (67.2%) devices. Only 15/201 (7.5%) AEDs had
      signage at a distance from AED itself. In only 5 of these cases (2.5%) was
      signage mounted more than 5.0 m from the AED. When signage was present, 46 used
      2008 ILCOR signage and 15 used 2006 Resuscitation Council (UK) signage. Signage
      visibility was partially or severely obstructed at 27/66 (40.9%) sites. None of
      the 45 GP surgeries surveyed used exterior signage or an exterior 24/7 access
      box. CONCLUSIONS: Current signage of PADs is poor and limits the device
      effectiveness by impeding public awareness and location of AEDs. Recommendations
      should promote visible signage within the operational radius of each AED.

PMID- 29654803
TI  - Donor cell chimerism evaluation in cerebrospinal fluid by short tandem repeat
      analysis following allogeneic hematopoietic stem cell transplantation.
AB  - Cerebrospinal fluid (CSF) cell count, morphology and flow cytometric evaluations
      are used to investigate central nervous system (CNS) involvement in
      leukemia/lymphoma. We performed CSF short tandem repeat (STR) analysis to monitor
      CSF chimerism status and evaluate for disease involvement in 11 asymptomatic
      pediatric allogeneic hematopoietic stem cell transplantation (HSCT) recipients
      with hemato-lymphoid neoplasms and high risk for or history of CNS involvement.
      Eighteen (64%) of the samples with median CSF cell count of 1/mm3 with 90%
      lymphocytes gave conclusive STR results, suggesting that this DNA-based method
      can be used in monitoring CSF chimerism status after HSCT with an acceptable
      yield.

PMID- 29654804
TI  - Prevalence of Post-Micturition Incontinence before and after Anterior
      Urethroplasty.
AB  - PURPOSE: In this study we aimed to define the prevalence of preoperative and
      postoperative post-micturition incontinence or post-void dribbling after anterior
      urethroplasty for urethral stricture disease. We also sought to determine risk
      factors for its presence. MATERIALS AND METHODS: We retrospectively reviewed a
      prospectively maintained, multi-institutional urethral stricture database to
      evaluate post-micturition incontinence using a single question from a validated
      questionnaire, "How often have you had a slight wetting of your pants a few
      minutes after you had finished urinating and had dressed yourself?" Possible
      answers were never-0 to all the time-3. The presence of post-micturition
      incontinence was defined as any answer greater than 0. Comparisons were made to
      stricture type and location, repair type and patient medical comorbidities.
      RESULTS: Preoperative and postoperative post-micturition incontinence
      questionnaires were completed by 614 and 331 patients, respectively. Patients
      without complete data available were excluded from study. Preoperative post
      micturition incontinence was present in 73% of patients, of whom 44% stated that
      this symptom was present most of the time. Overall postoperative post-micturition
      incontinence was present in 40% of patients and again it was not predicted by
      stricture location or urethroplasty type. Of the 331 patients with followup
      questionnaires 60% reported improvement, 32% reported no change and 8% reported
      worsening symptoms. The overall rate of de novo post-micturition incontinence was
      low at 6.3%. CONCLUSIONS: The prevalence of preoperative post-micturition
      incontinence is high and likely under reported. In most patients post-micturition
      incontinence improves after urethroplasty and the prevalence of de novo post
      micturition incontinence is low. The presence of post-micturition incontinence
      was not predicted by stricture length or location, or urethroplasty repair type.

PMID- 29654805
TI  - Efficacy and Safety of SER120 Nasal Spray in Patients with Nocturia: Pooled
      Analysis of 2 Randomized, Double-Blind, Placebo Controlled, Phase 3 Trials.
AB  - PURPOSE: SER120 desmopressin intranasal spray is the first U.S. Food and Drug
      Administration approved pharmacotherapy for nocturia. We evaluated its efficacy
      and safety in 2 randomized, double-blind, placebo controlled studies, DB3 and
      DB4. MATERIALS AND METHODS: A total of 1,333 intent to treat patients 50 years
      old or older with 2.16 or more nocturic voids per night during a 2-week screening
      period were randomized equally to SER120 intranasal spray 1.66 or 0.83 mcg, or
      placebo for a 12-week treatment. Co-primary end points were the mean change from
      baseline in nocturic episodes per night and the percent of patients with a 50% or
      greater reduction in mean nocturic episodes per night. Secondary end points were
      the validated INTU (Impact of Nighttime Urination) quality of life questionnaire
      in DB4, time to the first nocturic void and the percent of nights with 1 or fewer
      nocturic voids. RESULTS: Each SER120 dose showed statistical significance vs
      placebo for the 2 co-primary end points, including the mean nocturic episodes per
      night (-1.4 with 0.83 mcg and -1.5 with 1.66 mcg vs -1.2 with placebo, each p
      <0.0001), the percent of patients with a 50% or greater reduction in mean
      nocturic episodes per night (37.9% with 0.83 mcg and 48.7% with 1.66 mcg vs 30.3%
      with placebo, p = 0.0227 and <0.0001, respectively) as well as for all secondary
      end points in the pooled analyses. The 1.66 mcg dose demonstrated significant
      improvements in the INTU score (p = 0.0255). The incidence of hyponatremia,
      defined as serum sodium 125 mmol/l or less regardless of symptoms or less than
      130 mmol/l with symptoms, was 1.1%, 0% and 0.2% in the 1.66 and 0.83 mcg, and
      placebo groups, respectively. Other adverse events were similar across treatment
      groups. CONCLUSIONS: SER120 demonstrated significant improvements over placebo
      for co-primary and secondary efficacy end points that corresponded with quality
      of life improvements. SER120 at each dose had an acceptable safety profile.

PMID- 29654806
TI  - Targeted and random genetic modification of the black Sigatoka pathogen
      Pseudocercospora fijiensis by Agrobacterium tumefaciens-mediated transformation.

PMID- 29654807
TI  - Maternal fructose intake disturbs ovarian estradiol synthesis in rats.
AB  - AIMS: Recent increases in fructose consumption have raised concerns regarding the
      potential adverse intergenerational effects, as maternal fructose intake may
      induce physiological dysfunction in offspring. However, no reports are available
      regarding the effect of excess maternal fructose on reproductive tissues such as
      the ovary. Notably, the maternal intrauterine environment has been demonstrated
      to affect ovarian development in the subsequent generation. Given the fructose is
      transferred to the fetus, excess fructose consumption may affect offspring
      ovarian development. As ovarian development and its function is maintained by
      17beta-estradiol, we therefore investigated whether excess maternal fructose
      intake influences offspring ovarian estradiol synthesis. Rats received a 20%
      fructose solution during gestation and lactation. After weaning, offspring
      ovaries were isolated. KEY FINDINGS: Offspring from fructose-fed dams showed
      reduced StAR and P450(17alpha) mRNA levels, along with decreased protein
      expression levels. Conversely, attenuated P450arom protein level was found in the
      absence of mRNA expression alteration. Consistent with these phenomena, decreased
      circulating levels of estradiol were observed. Furthermore, estrogen receptor
      alpha (ERalpha) protein levels were also down-regulated. In accordance, the mRNA
      for progesterone receptor, a transcriptional target of ERalpha, was decreased.
      These results suggest that maternal fructose might alter ovarian physiology in
      the subsequent generation.

PMID- 29654808
TI  - On the role of cystatin C in cancer progression.
AB  - Cystatin C (Cyst C) is an endogenous inhibitor of lysosomal cysteine proteinases,
      which has been shown to play a role in several normal and pathological processes.
      Interestingly, a growing number of experimental and clinical studies suggest that
      this inhibitor also appears to be implicated in the malignant progression of
      various human tumors. However, the role of Cyst C in malignant diseases is still
      controversial as these studies have highlighted that this protein may function
      either as tumor suppressor or tumor promoter. The specific mechanisms underlying
      these opposing effects at present remain murky and are the subject of many
      current investigations. On the other hand, a complete knowledge of these
      mechanisms is of clinical interest in order to develop new, effective antitumor
      treatments based on the appropriate use of natural and/or synthetic cysteine
      proteinase inhibitors. This paper discusses the current findings regarding the
      role of Cyst C in cancer progression and the clinical implications emerging from
      these studies.

PMID- 29654809
TI  - Pituitary adenylate cyclase-activating polypeptide is a potent broad-spectrum
      antimicrobial peptide: Structure-activity relationships.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) is a naturally
      occurring cationic peptide with potent immunosuppressant and cytoprotective
      activities. We now show that full length PACAP38 and to a lesser extent, the
      truncated form PACAP27, and the closely related vasoactive intestinal peptide
      (VIP) and secretin had antimicrobial activity against the Gram-negative bacteria
      Escherichia coli in the radial diffusion assay. PACAP38 was more potent than
      either the bovine neutrophil antimicrobial peptide indolicidin or the synthetic
      antimicrobial peptide ARVA against E. coli. PACAP38 also had activity against the
      Gram-positive bacteria Staphylococcus aureus in the same assay with comparable
      potency to indolicidin and ARVA. In the more stringent broth dilution assay,
      PACAP38 had moderate sterilizing activity against E. coli, and potent sterilizing
      activity against the Gram-negative bacteria Pseudomonas aeruginosa. PACAP27, VIP
      and secretin were much less active than PACAP38 in this assay. PACAP38 also had
      some activity against the Gram-positive bacteria Bacillus cereus in the broth
      dilution assay. Many exopeptidase-resistant analogs of PACAP38, including both
      receptor agonists and antagonists, had antimicrobial activities equal to, or
      better than PACAP38, in both assays. PACAP38 made the membranes of E. coli
      permeable to SYTOX Green, suggesting a classical membrane lytic mechanism. These
      data suggest that analogs of PACPAP38 with a wide range of useful biological
      activities can be made by judicious substitutions in the sequence.

PMID- 29654810
TI  - Sustained improvement in hand hygiene compliance using a multi-modal improvement
      programme at a Swiss multi-site regional hospital.
AB  - BACKGROUND: Evidence of sustained improvement in hand hygiene compliance at the
      institutional level is scarce. AIM: To assess the impact and sustainability of a
      hospital-wide improvement programme on hand hygiene compliance of staff. METHODS:
      Analysis of trends of hand hygiene compliance for all clinical staff, measured
      through direct observation by trained observers, within a 450-bed multi-centre
      teaching hospital in the county of Neuchatel, Switzerland. INTERVENTION:
      Implementation of a multi-modal improvement programme based on the World Health
      Organization (WHO) strategy, with the goal of reaching overall compliance of at
      least 80%. The strategy content included increasing access to alcohol hand rub;
      healthcare worker education; two-month interval compliance measurement; and
      hospital-wide open communication about ward-level results, point-of-care
      reminders, communication via a dedicated in-house newsletter and leadership
      engagement. The implementation phase was followed by a consolidation phase.
      FINDINGS: In total, 33,476 observations were collected from September 2012 to
      March 2014 (mean >3000 opportunities per audit). Overall compliance improved from
      61.4% at baseline to 83.6% after the 18-month improvement programme (P<0.001),
      and was sustained at 85.3% 18 months later (i.e. 18 months after the programme
      finished) (P=0.08). The same trend (significant and clinically relevant
      improvement during the intervention, sustained after 18 months) was measured for
      all professional categories. CONCLUSIONS: This WHO-inspired improvement programme
      was associated with a significant improvement in hand hygiene compliance,
      globally and for each professional category. The results were sustained over an
      18-month period.

PMID- 29654811
TI  - Sepsis programme successes are responsible for the increased detection of
      bacteraemia.
AB  - BACKGROUND: Escherichia coli bacteraemia reduction targets are challenging but,
      in West Wales, this was the key infection surrogate measure set by the local
      health board in 2013, prior to the introduction of a Welsh Government target. The
      initial plateau of cases was not maintained and prompted this review. AIM: To
      review all blood cultures submitted between 2002 and 2016, both positive and
      negative. METHODS: With access to a microbiology data warehouse in Wales, all
      blood culture results were collected, extracted to Excel tables and analysed
      using change point analysis. FINDINGS: Just under 200,000 blood culture results
      were examined. This study found an increase in blood culture submissions, but the
      positivity rate remained constant throughout the period and the increased number
      of E. coli reflected the increased number of blood cultures taken. This
      demonstrated the success of sepsis awareness and the use of sepsis bundles for
      rapid diagnosis and management. CONCLUSION: Success in one area (sepsis
      management) conflicts with 'failure' in reducing E. coli bacteraemia. It is
      argued that targets need to be considered carefully in the light of all available
      information, which have currently set the National Health Service up to fail.

PMID- 29654813
TI  - Novel role of GLP-1 receptor signaling in energy expenditure during chronic high
      fat diet feeding in rats.
AB  - OBJECTIVE: Glucagon-like peptide-1 (GLP-1) secreted from intestinal L-cells plays
      a major role in meal termination and glucose-dependent insulin secretion. Several
      lines of evidence indicate, however, that the acute satiating and incretin
      effects of GLP-1 are attenuated with high fat diet (HFD) exposure. Here we tested
      the hypothesis that endogenous GLP-1 differentially affects energy balance and
      glucose homeostasis dependent on whether rats are fed chow or HFD (60% energy
      from fat). METHODS: We blocked GLP-1 receptor (GLP-1R) signaling by daily
      intraperitoneal (IP) injection of the GLP-1R antagonist exendin (9-39) (Ex9, 10
      MUg/kg) or vehicle for 5 weeks in male Sprague-Dawley rats fed either chow or
      HFD, recorded body weight (BW) and food intake throughout, and assessed energy
      expenditure (3rd week) and glucose tolerance (4th week). RESULTS: Five week daily
      Ex9 injections reduced BW gain in HFD-fed rats, but did not affect BW in chow-fed
      rats. On the other hand, chronic Ex9 treatment did not affect daily food intake
      in either chow or HFD-fed rats during the entire study. The reduced BW gain in
      HFD-fed rats was associated with an increase in energy expenditure.
      Interestingly, chronic Ex9 treatment induced glucose intolerance in chow-fed
      rats, but not in HFD-fed rats, suggesting a differential role of GLP-1R signaling
      in glucose metabolism during chow and HFD feeding. CONCLUSIONS: Our findings
      reveal a novel role of GLP-1R signaling, modulating energy expenditure rather
      than eating behavior during HFD feeding. Furthermore, these results suggest a
      previously unrecognized contribution of GLP-1R signaling to the pathophysiology
      of obesity.

PMID- 29654814
TI  - Cardiovascular outcomes of dipeptidyl peptidase-4 inhibitors in patients with
      type 2 diabetes on insulin therapy.
AB  - AIMS: To compare the hazard of cardiovascular diseases between DPP-4 inhibitor
      users and non-users who were on insulin therapy. METHODS: We conducted a
      population-based cohort study. 2652 patients with type 2 diabetes mellitus (T2DM)
      under insulin therapy were enrolled during 1997-2010. The incidence rates per
      1000 person-years (PYs) of stroke, coronary heart disease (CAD) and heart failure
      were compared between 1326 DPP-4 inhibitor users and 1326 propensity score
      matched non-users. Multivariable Cox proportional hazards model was used to
      evaluate excess risk of the DPP-4 inhibitor non-users. RESULTS: After adjustment
      of age, gender, comorbidities, drugs used and diabetes duration; the incidence
      rate per 1000 PYs were 21.70 and 9.88 in DPP-4 inhibitor non-users and users; DPP
      4 inhibitor users had lower hazard ratio (HR) of stroke (adjusted HR: 0.59, 95%
      CI: 0.42-0.83, p value: 0.002) compared with non-users. The incidence rates per
      1000 PYs of CAD and heart failure of control versus users were 19.85 versus 13.54
      and 5.56 versus 4.78; the adjusted HRs of CAD and heart failure were 0.86 and
      1.11. Both were non-significant. CONCLUSION: This nationwide study demonstrated
      that insulin plus DPP-4 inhibitor users had significantly lower risk of stroke as
      compared with non-users.

PMID- 29654812
TI  - Intermittent, extended access to preferred food leads to escalated food
      reinforcement and cyclic whole-body metabolism in rats: Sex differences and
      individual vulnerability.
AB  - Compulsive binge eating is a hallmark of binge eating disorder and bulimia
      nervosa and is implicated in some obesity cases. Eating disorders are sexually
      dimorphic, with females more often affected than males. Animal models of binge
      like eating based on intermittent access to palatable food exist; but, little is
      known regarding sex differences or individual vulnerability in these models with
      respect to the reinforcing efficacy of food, the development of compulsive- and
      binge-like eating, or associated changes in whole-body metabolism or body
      composition. Adolescent male (n = 24) and female (n = 32) Wistar rats were
      maintained on chow or a preferred, high-sucrose, chocolate-flavored diet in
      continuous or intermittent, extended access conditions. Body weight and
      composition, intake, fixed- and progressive-ratio operant self-administration,
      and whole body energy expenditure and respiratory exchange ratios were measured
      across an 11-week study period. Subgroup analyses were conducted to differentiate
      compulsive-like "high responder" intermittent access rats that escalated to
      extreme progressive-ratio self-administration performance vs. more resistant "low
      responders." Female rats had greater reinforcing efficacy of food than males in
      all diet conditions and were more often classified as "high responders". In both
      sexes, rats with intermittent access showed cycling of fuel substrate utilization
      and whole-body energy expenditure. Further, "high-responding" intermittent access
      female rats had especially elevated respiratory exchange ratios, indicating a fat
      sparing phenotype. Future studies are needed to better understand the molecular
      and neurobiological basis of the sex and individual differences we have observed
      in rats and their translational impact for humans with compulsive, binge eating
      disorders.

PMID- 29654815
TI  - Quantification of NK cell activity using whole blood: Methodological aspects of a
      new test.
AB  - Natural Killer (NK) cells are essential in the biological fight against cancer
      and intracellular pathogens, and their level of activity has in many settings
      been used as a biomarker for a functional immune response. Currently, NK cell
      activity is measured using either 51Cr-release assays or flow cytometry based
      assays revealing the cells' cytotoxic capacity or by stimulating them to produce
      cytokines. Although very effective, these are cumbersome techniques not suitable
      for high volume clinical laboratories. Recently, an assay has been introduced to
      measure NK cell activity in a simple and standardized manner. Following
      stimulation of NK cells in whole blood with a recombinant protein, it utilizes
      the concentration of IFNgamma released to the plasma as a surrogate marker for NK
      cell activity. However, whole blood holds several sources of IFNgamma which may
      blur the results and hamper the interpretation of the test. Therefore, the
      present study aimed at analyzing how specifically the test is measuring the
      activity of NK cells. Intracellular flow cytometry showed that NK cells, T cells,
      and Natural Killer T (NKT) cells were producing IFNgamma in the assay, however
      when analyzing the distribution of lymphocytes in the IFNgamma-expressing subset,
      the proportion of NK cells far exceeded the percentage of T-, and NKT cells (p <
      .0001). Hence, our data indicate that the readout of the test was indicative of
      the NK cells' ability to mount a response and thus the results may pave the way
      for the assay to become applicable in the clinical setting as an estimate of NK
      cell activity for both diagnostic and prognostic purposes.

PMID- 29654816
TI  - A novel method for sensitive, low-cost and portable detection of hepatitis B
      surface antigen using a personal glucose meter.
AB  - Hepatitis B virus (HBV) infection is the major public health problem leading
      cause of death worldwide. The most important diagnostic marker for this infection
      is hepatitis B surface antigen (HBsAg). In this study, a novel, inexpensive,
      portable and sensitive ELISA method was designed and investigated for diagnosis
      of HBsAg based on the functionalized Fe3O4 and Al2O3 nanoparticles, with the
      strategy for detecting the concentration of glucose using a cheap and accessible
      personal glucose meter (PGM). The ELISA system was constructed using hepatitis B
      antibody against HBsAg immobilized on streptavidin coated magnetic iron oxide
      particles (S-Fe3O4) as the capture antibody (Ab1). In addition, another hepatitis
      B antibody against different epitope of HBsAg (Ab2) and glucoamylase both were
      immobilized on Al2O3 nanoparticles. After formation of the sandwich immune
      complex between Ab1 and Ab2 immobilized on S-Fe3O4 and Al2O3 NPs, respectively,
      through HBsAg, starch was converted into glucose using glucoamylase. Then, the
      glucose concentration was measured using PGM. The concentration of HBsAg was
      calculated based on the linear relation between the concentrations of HBsAg and
      glucose. Under optimal conditions, this assay showed detection limit values of
      0.3 to 0.4 ng ml-1 for "ay" and "ad" subtypes of HBsAg, respectively. The results
      indicate that the designed assay is comparable to the commercial kits in terms of
      sensitivity, on-site, specificity, cost, simplicity, portability and
      reproducibility. The presented method can be used in disadvantaged areas of the
      world and blood transfusion centers. To the best of our knowledge, this is the
      first report of using PGMs for HBSAg detection.

PMID- 29654818
TI  - New insights into HDV-induced innate immunity: MDA5 senses HDV replication.

PMID- 29654817
TI  - Dysregulation of serum bile acids and FGF19 in alcoholic hepatitis.
AB  - BACKGROUND & AIMS: The degree of cholestasis is an important disease driver in
      alcoholic hepatitis, a severe clinical condition that needs new biomarkers and
      targeted therapies. We aimed to identify the largely unknown mechanisms and
      biomarkers linked to cholestasis in alcoholic hepatitis. METHODS: Herein, we
      analyzed a well characterized cohort of patients with alcoholic hepatitis and
      correlated clinical and histological parameters and outcomes with serum bile
      acids and fibroblast growth factor 19 (FGF19), a major regulator of bile acid
      synthesis. RESULTS: We found that total and conjugated bile acids were
      significantly increased in patients with alcoholic hepatitis compared with
      controls. Serum FGF19 levels were strongly increased and gene expression of FGF19
      was induced in biliary epithelial cells and ductular cells of patients with
      alcoholic hepatitis. De novo bile acid synthesis (CYP7A1 gene expression and C4
      serum levels) was significantly decreased in patients with alcoholic hepatitis.
      Importantly, total and conjugated bile acids correlated positively with FGF19 and
      with disease severity (model for end-stage liver disease score). FGF19 correlated
      best with conjugated cholic acid, and model for end-stage liver disease score
      best with taurine-conjugated chenodeoxycholic acid. Univariate analysis
      demonstrated significant associations between FGF19 and bilirubin as well as
      gamma glutamyl transferase, and negative correlations between FGF19 and fibrosis
      stage as well as polymorphonuclear leukocyte infiltration, in all patients with
      alcoholic hepatitis. CONCLUSION: Serum FGF19 and bile acids are significantly
      increased in patients with alcoholic hepatitis, while de novo bile acid synthesis
      is suppressed. Modulation of bile acid metabolism or signaling could represent a
      promising target for treatment of alcoholic hepatitis in humans. LAY SUMMARY:
      Understanding the underlying mechanisms that drive alcoholic hepatitis is
      important for the development of new biomarkers and targeted therapies. Herein,
      we describe a molecule that is increased in patients with alcoholic hepatitis.
      Modulating the molecular pathway of this molecule might lead to promising targets
      for the treatment of alcoholic hepatitis.

PMID- 29654820
TI  - The impact of acute thermal stress on green mussel Perna viridis: Oxidative
      damage and responses.
AB  - Examining the physiological responses of mussels to thermal stress is crucial to
      evaluate their biogeographic distribution and ability to adapt to a changing
      climate. In the present study, we investigated the effects of acute cold (8 
      degrees C and 15  degrees C) and heat (35  degrees C and 42  degrees C) stress on
      the mortality rate, reactive oxygen species (ROS) production, malondialdehyde
      (MDA) content, mitochondrial membrane potential (MMP) and antioxdative responses
      in the gill tissue of the green mussel species Perna viridis. Our results showed
      that cold and heat stress induced a temperature-dependent increase in mortality
      rate. ROS production increased significantly (p < 0.01) after both cold and heat
      stress. However, the activities of antioxidant enzymes, including SOD, CAT and
      GSH-Px, were greatly enhanced only after heat stress. In addition, MDA content
      and MMP increased significantly under both cold and heat stress. The up
      regulation of Hsp70 transcripts was only detected after acute stress at 35 
      degrees C. However, p38-MAPK phosphorylation levels increased after both cold and
      heat stress. In addition, a moderate activation of caspase-3 was found after
      mussels were exposed to 8  degrees C and 42  degrees C stress. Our results
      suggest that both extreme cold and heat stress could induce ROS production in the
      gill tissue of P. viridis, which might result in lipid peroxidation and
      mitochondria dysfunction. Antioxidative enzymes and Hsp70 might be important in
      the heat stress response of animals, whereas p38-MAPK might be crucial in the
      acute response to both cold and heat stress. However, caspase-3 activation might
      be very weak under both cold and heat stress.

PMID- 29654819
TI  - The telocytes/myofibroblasts 3-D network forms a stretch receptor in the human
      bladder mucosa. Is this structure involved in the detrusor overactive diseases?
AB  - Several connective tissue cells are present in the human bladder wall; among
      them, the myofibroblasts (MyF) and the so-called interstitial cells (IC) are a
      matter of investigation either by basic researchers or clinicians. The interest
      derives from the possibility that these two cell types could regulate the organ
      function forming a special sensory system in the bladder mucosa. Whereas
      attention for the myofibroblasts was mainly focused on understanding their role,
      the so-called IC are debatable starting from their nomenclature. Indeed, the IC
      should correspond to the previously called fibroblasts-like cells/interstitial
      Cajal-like cells (ICLC)/interstitial cells of Cajal (ICC) or PDGFRalpha positive
      cells, or CD34 positive cells. Recently a proper name was proposed to give them
      an identity, i.e. telocyte (TC). To date, this nomenclature is a better term than
      IC that is quite vague and can be used for all the cells that reside in the
      connective tissue. Noteworthy, in the bladder mucosa, TC and MyF form a hetero
      cellular 3-D network. The detrusor overactivity/overactive bladder (DO/OAB) are
      pathological conditions characterized by hypersensitivity to filling. It has been
      hypothesized that erroneous afferent inputs generated in the mucosa affect the
      efferent pathways and, consequently, the detrusor response. Presently, we review
      the literature regarding the presence and the potential role of TC and MyF in
      control conditions and in DO/OAB. On the possibility that the 3D-network made up
      by these two cell types might play a major role in the genesis of anomalous
      afferent stimuli will be given attention.

PMID- 29654821
TI  - PRISMA and AMSTAR show systematic reviews on health literacy and cancer screening
      are of good quality.
AB  - OBJECTIVES: The objectives of this study were to evaluate the reporting and
      methodological quality of systematic reviews (SRs) on health literacy and cancer
      screening and to investigate factors that may influence overall quality. STUDY
      DESIGN AND SETTING: We reviewed SRs published between 2009 and 2017. We
      calculated indices to represent the included SRs' adherence to Preferred
      Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and A
      Measurement Tool to Assess Systematic Reviews (AMSTAR). To assess possible
      determinants of SRs' quality, we regressed the index scores on year and region of
      publication, journal impact factor, authors' reported use of PRISMA, and presence
      of funding statements. RESULTS: We included 19 SRs, and median index scores were
      0.86 for PRISMA (interquartile range [IQR] = 0.11; range = 0.32-1.00) and 0.67
      for AMSTAR (IQR = 0.30; range = 0.22-1.00). Methodological and reporting problems
      pertained to protocol registration or publication, number of raters used, gray
      literature searches, excluded article lists, and unintegrated discussions of risk
      of bias and efficacy. Only journal impact factor was statistically significantly
      associated (positively) with PRISMA and AMSTAR index scores. CONCLUSION: The
      quality of SRs on health literacy and cancer screening was generally good.
      Systematic reviewers should register or publish their protocols, include PRISMA
      and AMSTAR checklists when submitting SRs to journals, and self-evaluate their
      SRs before submission.

PMID- 29654822
TI  - Considerations when assessing heterogeneity of treatment effect in patient
      centered outcomes research.
AB  - When baseline risk of an outcome varies within a population, the effect of a
      treatment on that outcome will vary on at least one scale (e.g., additive,
      multiplicative). This treatment effect heterogeneity is of interest in patient
      centered outcomes research. Based on a literature review and solicited expert
      opinion, we assert the following: (1) Treatment effect heterogeneity on the
      additive scale is most interpretable to health-care providers and patients using
      effect estimates to guide treatment decision-making; heterogeneity reported on
      the multiplicative scale may be misleading as to the magnitude or direction of a
      substantively important interaction. (2) The additive scale may give clues about
      sufficient-cause interaction, although such interaction is typically not relevant
      to patients' treatment choices. (3) Statistical modeling need not be conducted on
      the same scale as results are communicated. (4) Statistical testing is one tool
      for investigations, provided important subgroups are identified a priori, but
      test results should be interpreted cautiously given nonequivalence of statistical
      and clinical significance. (5) Qualitative interactions should be evaluated in a
      prespecified manner for important subgroups. Principled analytic plans that take
      into account the purpose of investigation of treatment effect heterogeneity are
      likely to yield more useful results for guiding treatment decisions.

PMID- 29654823
TI  - The Mechanical Revolution.

PMID- 29654824
TI  - Escherichia coli expression, purification, and refolding of human folate receptor
      alpha (hFRalpha) and beta (hFRbeta).
AB  - Human folate receptors (hFRalpha and hFRbeta) are membrane proteins anchored to
      the cell surface by glycosylphosphatidylinositol. They play an important role in
      cell growth by taking up folate for de novo synthesis of purines and methylation
      of DNA, lipids, and proteins. Thus, controlling folate uptake through hFRs may
      lead to the development of anti-cancer drugs. Development of hFRs-targeting drug
      requires a large amount of hFRs. However, it is difficult to prepare active forms
      of hFRs from prokaryotic cells because of their high content of cysteine residues
      that form disulfide bonds. Here, we prepared active forms of hFRalpha and hFRbeta
      from inclusion bodies of Escherichia coli. The crucial steps in our preparation
      were intensive washing of the inclusion bodies to remove impurities derived from
      E. coli and gradual dropping of solubilized hFRs into refolding buffers to
      correctly reform disulfide bonds. The binding activity of prepared hFRs to folate
      was confirmed by biolayer interferometry measurements. Finally, we successfully
      prepared the active form of 2.52 mg hFRalpha and 2.4 mg hFRbeta from 10 g of E.
      coli cell bodies.

PMID- 29654825
TI  - UDP-glucose pyrophosphorylase: Isolation, purification and characterization from
      developing thermotolerant wheat (Triticum aestivum) grains.
AB  - UDP-glucose pyrophosphorylase (UGPase, EC 2.7.7.9) activity was determined in
      four different thermotolerant varieties of wheat viz. WH-1021, PBW-373, Raj-3765
      and DBW-16. The specific activity of UGPase was found to be highest at 21 days
      after anthesis (DAA) in the variety WH-1021 which has been developed by Haryana
      Agricultural University, Hisar (Haryana, India). Hence, crude extract prepared
      from immature grains (21 days after anthesis) of WH-1021 was used for
      purification of UGPase using standard protein purification techniques which
      exploit differences in protein properties viz. ammonium sulphate fractionation
      (based on solubility differences), DEAE-ion exchange chromatography (based on
      charge differences) and molecular sieving through Sephadex G-100 gel (based on
      molecular mass differences). Near homogeneous enzyme preparation with molecular
      mass of 82 kDa and subunit molecular weight of 39 kDa was obtained. The purified
      enzyme had thermostability upto 50  degrees C. Kinetic studies revealed that the
      enzyme followed Michaelis Menten kinetics with Km value of 0.9 mM and 1.66 mM for
      UDP and PPi, respectively. Physico-chemical and kinetic characterization
      suggested that the enzyme UGPase from WH-1021 is a homodimer which has adapted to
      high temperature stress and that lower availability of substrates and high Km
      values may be responsible for reduced starch synthesis/grain yield.

PMID- 29654826
TI  - Real time quantitative analysis of lipid storage and lipolysis pathways by
      confocal spectral imaging of intracellular micropolarity.
AB  - Organisms store fatty acids in triacylglycerols in the form of lipid droplets, or
      hydrolyze triacylglycerols in response to energetic demands via activation of
      lipolytic or storage pathways. These pathways are complex sets of sequential
      reactions that are finely regulated in different cell types. Here we present a
      high spatial and temporal resolution-based method for the quantification of the
      turnover of fatty acids into triglycerides in live cells without introducing
      sample preparation artifacts. We performed confocal spectral imaging of
      intracellular micropolarity in cultured insulin secreting beta cells to detect
      micropolarity variations as they occur in time and at different pixels of
      microscope images. Acquired data are then analyzed in the framework of the
      spectral phasors technique. The method furnishes a metabolic parameter, which
      quantitatively assesses fatty acids - triacylglycerols turnover and the
      activation of lipolysis and storage pathways. Moreover, it provides a polarity
      profile, which represents the contribution of hyperpolar, polar and non-polar
      classes of lipids. These three different classes can be visualized on the image
      at a submicrometer resolution, revealing the spatial localization of lipids in
      cells under physiological and pathological settings. This new method allows for a
      fine-tuned, real-time visualization of the turnover of fatty acids into
      triglycerides in live cells with submicrometric resolution. It also detects
      imbalances between lipid storage and usage, which may lead to metabolic disorders
      within living cells and organisms.

PMID- 29654827
TI  - Palmitoyl lactic acid induces adipogenesis and a brown fat-like phenotype in 3T3
      L1 preadipocytes.
AB  - Brown adipose tissue is specialized to generate heat by dissipating chemical
      energy and may provide novel strategies for obesity treatment in humans.
      Recently, advances in understanding the pharmacological and dietary agents that
      contribute to the browning of white adipose tissue have been made to alleviate
      obesity by promoting energy expenditure. Krill oil is widely used as a health
      supplement in humans. In this study, the components from krill oil that promote
      adipogenesis of 3T3-L1 cells were screened to reveal palmitoyl lactic acid (PLA)
      as a promoter of adipogenesis. The PLA-induced adipocytes contained large number
      of small lipid droplets. Moreover, similar to the peroxisome proliferator
      activated receptor (PPAR)gamma agonists, pioglitazone and rosiglitazone, PLA
      significantly enhances adipogenesis in the presence of dexamethasone compared
      with PLA alone. Treatment with PLA causes a brown fat-like phenotype in 3T3-L1
      cells by enhanced expression of various brown/beige cell-specific genes, such as
      PR domain containing 16 (Prdm16) and peroxisome proliferative activated receptor,
      gamma, coactivator 1 alpha (Pgc1a), as well as adiponectin gene. The expression
      profile of the brown/beige cell-specific genes induced by PLA was similar to that
      of the PPARgamma agonist in 3T3-L1 cells. Our findings suggest that PLA induces a
      brown fat-like phenotype and, thus, likely has therapeutic potential in treating
      obesity.

PMID- 29654828
TI  - Fight or flight? Effects of vaginal oestrus on cortisol, testosterone, and
      behaviour in guinea pig female-female interaction.
AB  - It is accepted that social stress in relation to confrontation and competition
      can elicit behavioural and hormonal changes in social mammals. These effects
      have, however, been less frequently studied among female-female interactions. In
      the present study female-female confrontation experiments were carried out to
      monitor socio-positive and agonistic behaviour by controlling for the oestrus
      cycles of 12 individuals. Additionally, plasma cortisol (CORT) and testosterone
      (T) levels were determined before and after the experiments. During non-oestrus
      conditions a significant increase in CORT levels from pre- to post confrontation
      was registered and females spent more time to sit side by side. During vaginal
      oestrus the confrontation experiments revealed avoiding of a conspecific female
      by showing increased flight behaviour. However, during that period no changes in
      CORT levels were found. But, a non-significant increase in T was measured from
      pre- to post confrontation in both cycle phases, while no differences in the
      display of aggressive behaviours were found. These findings indicate considerable
      influences of different oestrus cycle phases on social stress-induced CORT
      secretion and the modulation of socio-positive and agonistic behaviour in female
      guinea pigs.

PMID- 29654829
TI  - Investigation of the therapy targets of Yi-Qi-Yang-Yin-Hua-Tan-Qu-Yu recipe on
      type 2 diabetes by serum proteome labeled with iTRAQ.
AB  - ETHNOPHARMACOLOGY RELEVANCE: Based on basic theories of Chinese medicine, Yi-Qi
      Yang-Yin-Hua-Tan-Qu-Yu (YQYYHTQY) recipe was constituted by eleven kinds of
      Chinese herbs and effective in treatment of type 2 diabetes (T2DM). But the
      therapy target was unclear. OBJECTIVE: In this study, we used the serum proteome
      labeled by iTRAQ to find therapy target of YQYYHTQY recipe on T2DM. MATERIALS AND
      METHODS: The rat model was induced by high-fat diet (HFD) and streptozotocin
      (STZ, 30 mg/kg). Drugs were administered to rats once daily for 14 days. Related
      laboratory parameters were observed. Serum proteome were compared between T2DM
      and YQYYHTQY group using the iTRAQ labeling quantitative proteomics technique.
      Functional differential proteins were analysis by STRING software. Target
      proteins were confirmed by ELISA kits. RESULTS: Hyperglycemia, hyperinsulinemia,
      insulin resistance, decrease of glucose transporter, depilation, less activity,
      flock together, depression, ecchymosis of tongue and tail appearance, the typical
      diabetic patients "a little more than three" symptoms, as well as the decrease of
      grip strength, serum cyclic adenosine monophosphate (cAMP)/ cyclic guanosine
      monophosphate (cGMP) ratio, serum high density lipoprotein-cholesterol (HDL-C)
      and the increase of serum triglyceride (TG), total cholesterol (TC), low density
      lipoprotein-cholesterol (LDL-C), thromboxane B2 (TXB2)/ 6-keto prostaglandin
      F1alpha (6-keto PGF1alpha) ratio, endothelin-1 (ET-1) levels were found in T2DM
      group. After drugs treatment, all the above indexes almost were improved in
      different degrees and effect of YQYYHTQY recipe was superior to pioglitazone
      hydrochloride. In addition, there were 23 differential proteins, 5 up-regulated
      and 18 down-regulated proteins. Of them, there were 4 proteins related with
      diabetes, blood and behavior. Cell division control protein 42 homolog (CDC42)
      and Ras homolog gene family member A (RhoA) were the therapy targets of YQYYHTQY
      recipe on T2DM. CONCLUSIONS: YQYYHTQY recipe showed therapy effect on T2DM. CDC42
      and RhoA proteins were the therapy targets of YQYYHTQY recipe.

PMID- 29654830
TI  - Neuronal erythropoietin overexpression is protective against kanamycin-induced
      hearing loss in mice.
AB  - Aminoglycosides have detrimental effects on the hair cells of the inner ear, yet
      these agents indisputably are one of the cornerstones in antibiotic therapy.
      Hence, there is a demand for strategies to prevent aminoglycoside-induced
      ototoxicity, which are not available today. In vitro data suggests that the
      pleiotropic growth factor erythropoietin (EPO) is neuroprotective against
      aminoglycoside-induced hair cell loss. Here, we use a mouse model with EPO
      overexpression in neuronal tissue to evaluate whether EPO could also in vivo
      protect from aminoglycoside-induced hearing loss. Auditory brainstem response
      (ABR) thresholds were measured in 12-weeks-old mice before and after treatment
      with kanamycin for 15 days, which resulted in both C57BL/6 and EPO-transgenic
      animals in a high-frequency hearing loss. However, ABR threshold shifts in EPO
      transgenic mice were significantly lower than in C57BL/6 mice (mean difference in
      ABR threshold shift 13.6 dB at 32 kHz, 95% CI 3.8-23.4 dB, p = 0.003).
      Correspondingly, quantification of hair cells and spiral ganglion neurons by
      immunofluorescence revealed that EPO-transgenic mice had a significantly lower
      hair cell and spiral ganglion neuron loss than C57BL/6 mice. In conclusion,
      neuronal overexpression of EPO is protective against aminoglycoside-induce
      hearing loss, which is in accordance with its known neuroprotective effects in
      other organs, such as the eye or the brain.

PMID- 29654831
TI  - Fingolimod interrupts the cross talk between estrogen metabolism and sphingolipid
      metabolism within prostate cancer cells.
AB  - Sphingolipids are critical regulators of tumor microenvironments and play an
      important role in estrogen-dependent cancers. Estrogen and estrogen metabolites
      were found to be involved in prostate cancer. Fingolimod (FTY720) is a
      sphingokinase-1 (SphK1) inhibitor with anticancer properties against various
      tumor cell types. Herein, we investigated the interference of FTY720 with the
      cross talk between sphingolipid metabolism and estrogen metabolism within
      prostate cancer cells. FTY720 showed cytotoxic antiproliferative effects against
      androgen-dependent and -independent prostate cancer cells with IC50 ranging from
      3.0 +/- 0.3 to 6.8 +/- 1.7 MUM. Exposure of prostate cancer cells to FTY720
      resulted in a dramatic decrease in the concentration of estradiol, estrone, 4
      hydroxyestradiol and 16alpha-hydroxyestrone compared to control cells. However,
      FTY720 significantly increased the concentration of 2-methoxyestrone and 2
      methoxyestradiol within prostate cancer cells. This was mirrored by significant
      downregulating of the expression of estrogen and catechol estrogen-synthesizing
      enzymes (CYP19, CYP1A1 and CYP1B1) within prostate cancer cells. On the other
      hand, FTY720 significantly upregulated the expression of catechol estrogen
      detoxifying enzyme (COMT). Additionally, FTY720 abolished estrogen-stimulated
      expression of ERalpha and basal expression of ERbeta within prostate cancer
      cells. Furthermore, FTY720 suppressed the expression of the ER-downstream
      regulated genes, CXCR4 and cyclin D1. Reciprocally, it was found that estradiol
      and catechol estrogens significantly induced the expression of SphK1 while
      methoxylated catechol estrogen suppressed its expression within prostate cancer
      cells in a dose-dependent manner. Current research has highlighted the hazardous
      influence of the estrogenic component to prostate cancer. We found that
      fingolimod (FTY720) could modulate the estrogenic micromilieu and interrupt its
      cross talk with sphingolipid metabolism.

PMID- 29654832
TI  - Enhancing fructosylated chondroitin production in Escherichia coli K4 by
      balancing the UDP-precursors.
AB  - Microbial production of chondroitin and chondroitin-like polysaccharides from
      renewable feedstock is a promising and sustainable alternative to extraction from
      animal tissues. In this study, we attempted to improve production of
      fructosylated chondroitin in Escherichia coli K4 by balancing intracellular
      levels of the precursors UDP-GalNAc and UDP-GlcA. To this end, we deleted pfkA to
      favor the production of Fru-6-P. Then, we identified rate-limiting enzymes in the
      synthesis of UDP-precursors. Third, UDP-GalNAc synthesis, UDP-GlcA synthesis, and
      chondroitin polymerization were combinatorially optimized by altering the
      expression of relevant enzymes. The ratio of intracellular UDP-GalNAc to UDP-GlcA
      increased from 0.17 in the wild-type strain to 1.05 in a 30-L fed-batch culture
      of the engineered strain. Titer and productivity of fructosylated chondroitin
      also increased to 8.43 g/L and 227.84 mg/L/h; the latter represented the highest
      productivity level achieved to date.

PMID- 29654833
TI  - Improved riboflavin production with Ashbya gossypii from vegetable oil based on
      13C metabolic network analysis with combined labeling analysis by GC/MS, LC/MS,
      1D, and 2D NMR.
AB  - The fungus Ashbya gossypii is an important industrial producer of riboflavin,
      i.e. vitamin B2. In order to meet the constantly increasing demands for improved
      production processes, it appears essential to better understand the underlying
      metabolic pathways of the vitamin. Here, we used a highly sophisticated set-up of
      parallel 13C tracer studies with labeling analysis by GC/MS, LC/MS, 1D, and 2D
      NMR to resolve carbon fluxes in the overproducing strain A. gossypii B2 during
      growth and subsequent riboflavin production from vegetable oil as carbon source,
      yeast extract, and supplemented glycine. The studies provided a detailed picture
      of the underlying metabolism. Glycine was exclusively used as carbon-two donor of
      the vitamin's pyrimidine ring, which is part of its isoalloxazine ring structure,
      but did not contribute to the carbon-one metabolism due to the proven absence of
      a functional glycine cleavage system. The pools of serine and glycine were
      closely connected due to a highly reversible serine hydroxymethyltransferase.
      Transmembrane formate flux simulations revealed that the one-carbon metabolism
      displayed a severe bottleneck during initial riboflavin production, which was
      overcome in later phases of the cultivation by intrinsic formate accumulation.
      The transiently limiting carbon-one pool was successfully replenished by time
      resolved feeding of small amounts of formate and serine, respectively. This
      increased the intracellular availability of glycine, serine, and formate and
      resulted in a final riboflavin titer increase of 45%.

PMID- 29654834
TI  - Characterization of three multicopper oxidases in the filamentous fungus
      Podospora anserina: A new role of an ABR1-like protein in fungal development?
AB  - The Podospora anserina genome contains a large family of 15 multicopper oxidases
      (MCOs), including three genes encoding a FET3-like protein, an ABR1-like protein
      and an ascorbate oxidase (AO)-like protein. FET3, ABR1 and AO1 are involved in
      global laccase-like activity since deletion of the relevant genes led to a
      decrease of activity when laccase substrate (ABTS) was used as substrate.
      However, contrary to the P. anserina MCO proteins previously characterized, none
      of these three MCOs seemed to be involved in lignocellulose degradation and in
      resistance to phenolic compounds and oxidative stress. We showed that the bulk of
      ferroxidase activity was clearly due to ABR1, and only in minor part to FET3,
      although ABR1 does not contain all the residues typical of FET3 proteins.
      Moreover, we showed that ABR1, related to the Aspergillus fumigatus ABR1 protein,
      was clearly and specifically involved in pigmentation of ascospores.
      Surprisingly, phenotypes were more severe in mutants lacking both abr1 and ao1.
      Deletion of the ao1 gene led to an almost total loss of AO activity. No direct
      involvement of AO1 in fungal developmental process in P. anserina was evidenced,
      except in a abr1Delta background. Overall, unlike other previously characterized
      MCOs, we thus evidence a clear involvement of ABR1 protein in fungal development.

PMID- 29654835
TI  - The role of inflammation in subventricular zone cancer.
AB  - The adult subventricular zone (SVZ) stem cell niche has proven vital for
      discovering neurodevelopmental mechanisms and holds great potential in medicine
      for neurodegenerative diseases. Yet the SVZ holds a dark side - it can become
      tumorigenic. Glioblastomas can arise from the SVZ via cancer stem cells (CSCs).
      Glioblastoma and other brain cancers often have dismal prognoses since they are
      resistant to treatment. In this review we argue that the SVZ is susceptible to
      cancer because it contains stem cells, migratory progenitors and unusual
      inflammation. Theoretically, SVZ stem cells can convert to CSCs more readily than
      can postmitotic neural cells. Additionally, the robust long-distance migration of
      SVZ progenitors can be subverted upon tumorigenesis to an infiltrative phenotype.
      There is evidence that the SVZ, even in health, exhibits chronic low-grade
      cellular and molecular inflammation. Its inflammatory response to brain injuries
      and disease differs from that of other brain regions. We hypothesize that the SVZ
      inflammatory environment can predispose cells to novel mutations and exacerbate
      cancer phenotypes. This can be studied in animal models in which human mutations
      related to cancer are knocked into the SVZ to induce tumorigenesis and the CSC
      immune interactions that precede full-blown cancer. Importantly inflammation can
      be pharmacologically modulated providing an avenue to brain cancer management and
      treatment. The SVZ is accessible by virtue of its location surrounding the
      lateral ventricles and CSCs in the SVZ can be targeted with a variety of
      pharmacotherapies. Thus, the SVZ can yield aggressive tumors but can be targeted
      via several strategies.

PMID- 29654836
TI  - Homeostatic and regenerative neurogenesis in salamanders.
AB  - Large-scale regeneration in the adult central nervous system is a unique capacity
      of salamanders among tetrapods. Salamanders can replace neuronal populations,
      repair damaged nerve fibers and restore tissue architecture in retina, brain and
      spinal cord, leading to functional recovery. The underlying mechanisms have long
      been difficult to study due to the paucity of available genomic tools. Recent
      technological progress, such as genome sequencing, transgenesis and genome
      editing provide new momentum for systematic interrogation of regenerative
      processes in the salamander central nervous system. Understanding central nervous
      system regeneration also entails designing the appropriate molecular, cellular,
      and behavioral assays. Here we outline the organization of salamander brain
      structures. With special focus on ependymoglial cells, we integrate cellular and
      molecular processes of neurogenesis during developmental and adult homeostasis as
      well as in various injury models. Wherever possible, we correlate developmental
      and regenerative neurogenesis to the acquisition and recovery of behaviors.
      Throughout the review we place the findings into an evolutionary context for
      inter-species comparisons.

PMID- 29654837
TI  - Restoration of short chain fatty acid and bile acid metabolism following fecal
      microbiota transplantation in patients with recurrent Clostridium difficile
      infection.
AB  - A significant proportion of individuals develop recurrent Clostridium difficile
      infection (CDI) following initial disease. Fecal microbiota transplantation
      (FMT), a highly effective treatment method for recurrent CDI, has been
      demonstrated to induce microbiota recovery. One of the proposed functions
      associated with restoration of colonization resistance against C. difficile has
      been recovery of bile acid metabolism. In this study, we aimed to assess recovery
      of short chain fatty acids (SCFAs) in addition to bile acids alongside microbial
      community structure in six patients with recurrent CDI following treatment with
      FMT over time. Using 16S rRNA gene-based sequencing, we observed marked
      similarity of the microbiota between recipients following FMT (n = 6, sampling up
      to 6 months post-FMT) and their respective donors. Sustained increases in the
      levels of the SCFAs butyrate, acetate, and propionate were observed post-FMT, and
      variable recovery over time was observed in the secondary bile acids deoxycholate
      and lithocholate. To correlate these changes with specific microbial taxa at an
      individual level, we applied a generalized estimating equation approach to model
      metabolite concentrations with the presence of specific members of the
      microbiota. Metabolites that increased following FMT were associated with
      bacteria classified within the Lachnospiraceae, Ruminococcaceae, and unclassified
      Clostridiales families. In contrast, members of these taxa were inversely
      associated with primary bile acids. The longitudinal aspect of this study allowed
      us to characterize individualized patterns of recovery, revealing variability
      between and within patients following FMT.

PMID- 29654838
TI  - Neighbourhood safety and smoking in population subgroups: The HELIUS study.
AB  - This study examines the associations between neighbourhood safety and three types
      of smoking behaviour, and whether these associations differ by sex, age,
      ethnicity and individual-level socio-economic position. Baseline data (2011-2015)
      from the The HEalthy LIfe in an Urban Setting (HELIUS) study (Amsterdam, the
      Netherlands) were used. Smoking behaviour was based on self-report. Heavy smoking
      was defined as smoking >=10 cigarettes per day. Nicotine dependence was assessed
      using the Fagerstrom questionnaire. Geographic Information System techniques were
      used to construct local residential areas and to examine neighbourhood safety for
      these areas using micro-scale environmental data. Multilevel logistic regression
      analyses with 6-digit zip code area as a second level were used to assess the
      association between neighbourhood safety and smoking. In our study sample of
      22,728 participants (18-70 years), 24.0% were current smokers, 13.7% were heavy
      smokers and 8.1% were nicotine dependent individuals. Higher levels of
      neighbourhood safety were significantly associated with less heavy smoking (OR =
      0.88, 95% CI = 0.78-0.99) and less nicotine dependence (OR = 0.81, 95% CI = 0.69
      0.95), but not with less current smoking (OR = 1.01, 95% CI = 0.91-1.11). The
      associations between neighbourhood safety and the three types of smoking
      behaviour varied by ethnicity. For instance, higher levels of neighbourhood
      safety were associated with less current smoking in participants of African
      Surinamese origin (OR = 0.71, 95% CI = 0.57-0.89), but not in those of Dutch (OR
      = 1.13, 95% CI = 0.91-1.39), South-Asian Surinamese (OR = 1.22, 95% CI = 0.95
      1.55), Turkish (OR = 1.08, 95% CI = 0.84-1.38), Moroccan (OR = 1.53, 95% CI =
      1.12-2.10) or Ghanaian (OR = 1.18, 95% CI = 0.47-2.94) origin. Policies that
      improve neighbourhood safety potentially contribute to less heavy smoking and
      nicotine dependence.

PMID- 29654839
TI  - Risk factors associated with multiple correlated health outcomes in the 500
      Cities Project.
AB  - Reducing chronic disease is a major health challenge. Risk factors for chronic
      diseases are often studied at the individual level, even though interventions and
      policies may be implemented at the city level. We use an ecologic study design
      with city-level data, to simultaneously assess the relative impact of unhealthy
      behaviors and preventive care measures on multiple chronic disease health
      outcomes. We analyze a newly available, large national dataset called the 500
      Cities Project. We examine the associations between city-level prevalence of
      unhealthy behaviors, clinical preventive service use, and all chronic disease
      health outcomes in 500 of the largest U.S. cities for year 2014. After adjusting
      for age and demographic characteristics, using MANOVA we found that the top three
      risk factors for all health outcomes are smoking (Pillai's trace = 0.95, approx.
      F = 688.7, p-value < 0.0001), lack of physical activity (Pillai's trace = 0.91,
      approx. F = 380.0, p-value < 0.0001) and binge drinking (Pillai's trace = 0.91,
      approx. F = 348.8, p-value < 0.0001), which are statistically significant after
      adjusting for multiple comparisons. Higher prevalence of an annual dental
      checkup, a preventive service use measure, is correlated with lower prevalence of
      several chronic diseases such as diabetes (correlation coefficient r = -0.88),
      poor physical health (r = -0.91), stroke (r = -0.85), cardiovascular disease (r =
      -0.83) and poor mental health (r = -0.82). Identifying important chronic disease
      risk factors at the city-level may provide more actionable information for
      policymakers to improve urban health.

PMID- 29654840
TI  - Efficacy of Acupuncture in the Management of Primary Dysmenorrhea: A Randomized
      Controlled Trial.
AB  - INTRODUCTION: Dysmenorrhea constitutes one of the most frequent disorders in
      women of a fertile age. The present study was conducted to evaluate the efficacy
      of acupuncture in the management of primary dysmenorrhea. MATERIALS AND METHODS:
      Sixty females aged 17-23 years were randomly assigned to either a study group or
      a control group. The study group received acupuncture for the duration of 20
      minutes/day, for 15 days/month, for the period of 90 days. The control group did
      not receive acupuncture for the same period. Baseline, during, and post
      assessments of both the groups were taken on day 1; day 30 and day 60; and day
      90, respectively. Statistical analysis was performed by repeated measures of
      analysis of variance followed by post hoc analysis with Bonferroni adjustment for
      multiple comparisons, independent samples t test for visual analog scale score,
      and Mann-Whitney U test for rest of the variables using statistical package for
      the social sciences, version 16. RESULTS: This study showed a significant
      reduction in all the variables such as the visual analog scale score for pain,
      menstrual cramps, headache, dizziness, diarrhea, faint, mood changes, tiredness,
      nausea, and vomiting in the study group compared with those in the control group.
      CONCLUSION: Acupuncture could be considered as an effective treatment modality
      for the management of primary dysmenorrhea.

PMID- 29654841
TI  - Comparison of the Prophylactic Effect Between Acupuncture and Acupressure on
      Menstrual Migraine: Results of a Pilot Study.
AB  - OBJECTIVES: To compare between acupuncture and acupressure for preventing
      menstrual migraine (MM). METHODS: MM is one kind of migraine associated with
      menses in female. It is often associated with increased menstrual distress and
      disability, leading to decreased daily activity and quality of life. A randomized
      and controlled pilot study was conducted with three groups: verum acupuncture
      (VA) group, acupressure (AP) group, and control acupuncture (CA) group. The study
      lasted for 7 cycle-months, with a 1 cycle-month baseline observation (T1), a 3
      cycle-month intervention (3 times per cycle-month) (T2-T4), and a 3 cycle-month
      follow-up (T5-T7). Outcome measures were number of migraine days, average and
      peak pain, total duration period of MM, and percentage of patients with >=50%
      reduction in the number of MM days. RESULTS: A total of 18 participants were
      included in the analysis (VA, n = 7; AP, n = 6; CA, n = 5). Both VA and AP were
      significantly more effective than CA for reducing MM days during the intervention
      period. Both VA and AP tended to be more effective than CA for reducing peak pain
      during the intervention period. No significant differences for the outcomes were
      observed among VA, AP, and CA during the follow-up period. No serious adverse
      events were reported. DISCUSSION: Results of the pilot study suggest that both VA
      and AP could be considered as alternative and safe prophylactic interventions for
      MM. Register ClinicalTrials.gov Identifier: NCT02592681.

PMID- 29654842
TI  - Optical techniques for the diagnosis and treatment of lesions induced by the
      human papillomavirus - A resource letter.
AB  - Human papillomaviruses (HPV) are the most common sexually-transmitted virus, and
      carcinogenic HPV strains are reported to be responsible for virtually all cases
      of cervical cancer and its precursor, the cervical intraepithelial neoplasia
      (CIN). About 30% of the sexually active population are considered to be affected
      by HPV. Around 600 million people are estimated to be infected worldwide.
      Diseases related to HPV cause significant impact from both the personal welfare
      point of view and public healthcare perspective. This resource letter collects
      relevant information regarding HPV-induced lesions and discusses both diagnosis
      and treatment, with particular attention to optical techniques and the challenges
      involved to the implementation of those approaches.

PMID- 29654843
TI  - Regarding "Understanding the Legal Essentials of a Bowel Injury Lawsuit in
      Minimally Invasive Gynecologic Surgery".

PMID- 29654844
TI  - Oxidative stress and dietary micronutrient deficiencies contribute to
      overexpression of epigenetically regulated genes by lupus T cells.
AB  - Patients with active lupus have altered T cells characterized by low DNA
      methyltransferase levels. We hypothesized that low DNA methyltransferase levels
      synergize with low methionine levels to cause greater overexpression of genes
      normally suppressed by DNA methylation. CD4+ T cells from lupus patients and
      controls were stimulated with PHA then cultured in custom media with normal or
      low methionine levels. Oxidative stress was induced by treating the normal CD4+ T
      cells with peroxynitrite prior to culture. Methylation sensitive gene expression
      was measured by flow cytometry. Results showed low methionine levels caused
      greater overexpression of methylation sensitive genes in peroxynitrite treated T
      cells relative to untreated T cells, and in T cells from lupus patients relative
      to T cells from healthy controls. In conclusion, low dietary transmethylation
      micronutrient levels and low DNA methyltransferase levels caused either by
      oxidative stress or lupus, have additive effects on methylation sensitive T cell
      gene expression.

PMID- 29654845
TI  - Immune senescence, epigenetics and autoimmunity.
AB  - Aging of the immune system in humans and animals is characterized by a decline in
      both adaptive and innate immune responses. Paradoxically, aging is also
      associated with a state of chronic inflammation ("inflammaging") and an increased
      likelihood of developing autoimmune diseases. Epigenetic changes in non-dividing
      and dividing cells, including immune cells, due to environmental factors
      contribute to the inflammation and autoimmunity that characterize both the state
      and diseases of aging. Here, we review the epigenetic mechanisms involved in the
      development of immune senescence and autoimmunity in old age.

PMID- 29654846
TI  - Formation and fate of DNA adducts of alpha- and beta-asarone in rat hepatocytes.
AB  - While alpha-asarone (aA) and beta-asarone (bA) are genotoxic and were shown to be
      carcinogenic the mechanisms underlying these effects are not understood. Major
      metabolites of both compounds are epoxides which are mutagenic in the Ames test.
      We investigated their reactivity towards nucleosides and identified epoxide
      derived DNA adducts with 2'-deoxyadenosine (dA) and 2'-deoxyguanosine (dG) using
      UPLC-UV/VIS, LC-MS/MS and NMR spectroscopy. The adducts were characterized as N6
      1'-hydroxy-dihydro-asarone-dA and N2-1'-hydroxy-dihydro-asarone-dG. Chemical
      synthesis of these adducts, isotope labeled standards and development of a
      sensitive and specific isotope dilution mass spectrometric method allowed the
      quantification of DNA adducts formed in primary rat hepatocytes incubated with aA
      or bA over up to 48 h. We observed a concentration-dependent, nearly linear
      formation of DNA adducts, which was higher for bA than for aA. In time course
      experiments, the amount of DNA adducts reached a maximum within the first 6 h.
      Over the next 42 h, the amount of DNA adducts decreased, however DNA adducts were
      still detectable even at the lowest substrate concentration of 10 MUM. These
      results clearly show that aA and bA are able to form epoxide-derived DNA adducts
      in mammalian cells which may be responsible for their genotoxic, mutagenic and
      carcinogenic mode of action.

PMID- 29654847
TI  - Alleviative effect of resveratrol on polyvinyl chloride-induced reproductive
      toxicity in male Wistar rats.
AB  - The present study was aimed to investigate the effect of PVC on reproductive
      competence in adult male Wistar rats. Further, the study also encompasses the
      protective effect of trans-resveratrol on PVC-induced reproductive toxicity in
      rats. Adult male rats weighing 210-240 g were administered with either PVC at two
      different doses 100 and 500 mg/kg body weight, orally, daily for 60 days or
      resveratrol (20 mg/kg body weight/day) through gavage for 60 days on alternate
      days or both PVC (500 mg/kg body weight) and resveratrol. The results revealed
      significant reduction in the weights of reproductive organs, epididymal sperm
      count, viable-, motile-, and HOS-tail coiled sperm and testicular daily sperm
      production, steroidogenic enzyme activities, serum testosterone levels in PVC
      treated rats. Conversely the levels of lipid peroxidation increased significantly
      with a decrease in activity levels of antioxidant enzymes in the testis of PVC
      exposed rats. Exposure to PVC resulted in reduction in epithelial thickness and
      seminiferous tubule diameter. No significant changes in the selected reproductive
      variables were observed in the resveratrol alone treated control rats, whereas,
      co-administration of resveratrol and PVC resulted in a significant improvement in
      steroidogenesis and spermatogenesis and mitigated oxidative stress over PVC
      exposed rats.

PMID- 29654848
TI  - A 90-day OECD TG 413 rat inhalation study with systems toxicology endpoints
      demonstrates reduced exposure effects of the aerosol from the carbon heated
      tobacco product version 1.2 (CHTP1.2) compared with cigarette smoke. I.
      Inhalation exposure, clinical pathology and histopathology.
AB  - Within the framework of a systems toxicology approach, the inhalation toxicity of
      aerosol from a novel tobacco-heating potentially modified risk tobacco product
      (MRTP), the carbon-heated tobacco product (CHTP) 1.2, was characterized and
      compared with that of mainstream smoke (CS) from the 3R4F reference cigarette in
      a 90-day nose-only rat inhalation study in general accordance with OECD TG 413.
      CHTP1.2 is a heat-not-burn product using a carbon heat source to produce an
      aerosol that contains nicotine and tobacco flavor. At equal or twice the nicotine
      concentration in the test atmospheres, inhalation of CHTP1.2 aerosol led to a
      significantly lower exposure to harmful constituents and induced less respiratory
      tract irritation, systemic, and pathological effects compared with CS. Nasal
      epithelial changes were less pronounced in the CHTP1.2- than in the CS-exposed
      groups and reverted in the nicotine concentration-matched group after a recovery
      period. Lung inflammation was minimal in the CHTP1.2-treated groups compared with
      the moderate extent seen in the 3R4F groups. Many other toxicological endpoints
      evaluated did not show CHTP1.2 aerosol exposure-related effects, and no effects
      not seen for 3R4F were observed. These observations were consistent with findings
      from previous studies in which rats were exposed to MRTP aerosols containing
      similar nicotine concentrations.

PMID- 29654849
TI  - Effects of metformin, rosiglitazone and insulin on bone metabolism in patients
      with type 2 diabetes.
AB  - BACKGROUND: Fracture risk is increased in individuals with type 2 diabetes (T2D).
      The pathophysiological mechanisms accentuating fracture risk in T2D are
      convoluted, incorporating factors such as hyperglycaemia, insulinopenia, and
      antidiabetic drugs. The objectives of this study were to assess whether different
      insulin regimens, metformin and rosiglitazone influence bone metabolism. We
      explored if the concentration of metformin and rosiglitazone in blood or improved
      glycaemic control altered bone turnover. METHODS: Two-year clinical trial
      designed to investigate effects of antidiabetic treatment in 371 T2D patients.
      Participants were randomized to short or long-acting human insulin (non-blinded)
      and then further randomized to metformin + placebo, rosiglitazone + placebo,
      metformin + rosiglitazone or placebo + placebo (blinded). Fasting bone turnover
      markers (BTM) representing bone resorption (CTX) and formation (PINP) including
      HbA1c were measured at baseline and after 3, 12 and 24 months. Trough steady
      state plasma concentrations of metformin and rosiglitazone were measured after 3,
      6 and 9 months of treatment. Associations between treatments and BTMs during the
      follow-up of the trial were analysed in mixed-effects models that included
      adjustments for age, gender, BMI, renal function and repeated measures of HbA1c.
      RESULTS: BTMs increased from baseline to month 12 and remained higher at month
      24, with CTX and PINP increasing 28.5% and 23.0% (all: p < 0.001), respectively.
      Allocation of insulin regimens was not associated with different levels of BTMs.
      Metformin and metformin + rosiglitazone but not rosiglitazone alone were
      associated with lower bone formation (PINP). Neither metformin nor rosiglitazone
      plasma concentrations was associated with BTMs. HbA1c was inversely associated
      with CTX but not P1NP. CONCLUSIONS: The choice of insulin treatment is not
      influencing BTMs, metformin treatment may decrease BTMs, and improvement of
      glycaemic control may influence bone resorption activity.

PMID- 29654850
TI  - Satiation deficits and binge eating: Probing differences between bulimia nervosa
      and purging disorder using an ad lib test meal.
AB  - Purging disorder (PD) has been included as a named condition within the DSM-5
      category of Other Specified Feeding or Eating Disorder and differs from bulimia
      nervosa (BN) in the absence of binge-eating episodes. The current study evaluated
      satiation through behavioral and self-report measures to understand how this
      construct may explain distinct symptom presentations for bulimia nervosa (BN) and
      purging disorder (PD). Women (N = 119) were recruited from the community if they
      met DSM-5 criteria for BN (n = 57), PD (n = 31), or were free of eating pathology
      (n = 31 controls). Participants completed structured clinical interviews and
      questionnaires and an ad lib test meal during which they provided reports of
      subjective states. Significant group differences were found on self-reported
      symptoms, ad lib test meal intake, and subjective responses to food intake
      between individuals with eating disorders and controls and between BN and PD.
      Further, ad lib intake was associated with self-reported frequency and size of
      binge episodes. In a multivariable model, the amount of food consumed during
      binges as reported during clinical interviews predicted amount of food consumed
      during the ad lib test meal, controlling for other binge-related variables.
      Satiation deficits distinguish BN from PD and appear to be specifically linked to
      the size of binge episodes. Future work should expand exploration of
      physiological bases of these differences to contribute to novel interventions.

PMID- 29654851
TI  - The relation between family meals and health of infants and toddlers: A review.
AB  - Family meals are associated with multiple health benefits in children and
      adolescents including evidence that eating together as a family may play a role
      in reducing childhood obesity. The current review aims to investigate whether the
      beneficial health effects of the family meal also apply to infants and toddlers.
      PubMed, Web of Science, Scopus and PsycInfo were searched and 14 empirical
      studies were identified. The findings were discussed according to frequency of
      having a family meal and parental perception, associations between the family
      meal and health aspects (e.g., eating behaviors and diet quality) and causal
      influences of these associations. Descriptive data showed that mothers offer food
      at a structured mealtime, but that eating together as a family was not always
      upheld. The frequency of family meals was positively associated with more
      nutrient-dense food intake and a more balanced diet. Different advantages (e.g.,
      social importance, practical considerations) and obstacles (e.g., planning,
      possible mess) of the family meal were mentioned by parents. Further, having
      structured mealtimes and family meals was associated with more food enjoyment and
      less fussy and emotional eating. Finally, no causal studies were identified. The
      limited number of studies suggests that the pattern of positive associations
      between family meal and child health which has been shown in older children may
      also exist in infants and toddlers. More specific research is needed to examine
      the causality of the associations between the family meal and health of the
      infant and toddler. The associations between the family meal and less fussiness
      and emotional eating, more food enjoyment and better nutrient intake suggest that
      the family meal is a valuable moment to promote healthy eating in toddlers and
      infants.

PMID- 29654852
TI  - The effects of scheduled running wheel access on binge-like eating behavior and
      its consequences.
AB  - Binge eating disorder (BED) is an eating disorder involving repeated,
      intermittent over consumption of food in brief periods of time, usually with no
      compensatory behaviors. There are few successful treatments and the underlying
      neural mechanisms remain unclear. In the current study, we hypothesized that
      voluntary running wheel (RW) activity could reduce binge-like eating behavior in
      a rat model. Rats were given intermittent (3 times/wk) limited (1hr) access to a
      high-fat food (Crisco), in addition to continuously available chow. Crisco was
      available every Mon, Wed, and Fri for 1hr before dark onset. Rats were divided
      into 2 groups: those with RW access during the first half of the experiment and
      sedentary during the second half (RW-SED) and those that were sedentary during
      the first half of the experiment and had RW access during the second half (SED
      RW). Crisco intake was significantly less in both groups during the period of
      time with a RW present. Within the bingeing RW-SED rats, the gene expression of
      the orexigenic neuropeptides AgRP and NPY were similar to a non-bingeing
      sedentary control (CON) group, while the expression of the anorexigenic
      neuropeptide POMC was significantly increased relative to the SED-RW and CON
      groups. Despite elevated POMC, the rats continued to binge. Additionally, within
      both groups, the gene expression of the D2R and Oprm1 in the NAc and the VTA were
      altered suggesting that the reward system was stimulated by both the bingeing
      behavior and the running wheel activity. Overall, access to a RW and the
      resulting activity significantly reduced binge-like behavior as well as modulated
      the effects of binging on brain appetite and reward systems.

PMID- 29654853
TI  - Antiarrhythmic effects of stimulating the left dorsal branch of the thoracic
      nerve in a canine model of paroxysmal atrial tachyarrhythmias.
AB  - BACKGROUND: Stellate ganglion nerve activity (SGNA) precedes paroxysmal atrial
      tachyarrhythmia (PAT) episodes in dogs with intermittent rapid left atrial (LA)
      pacing. The left dorsal branch of the thoracic nerve (LDTN) contains sympathetic
      nerves originating from the stellate ganglia. OBJECTIVE: The purpose of this
      study was to test the hypothesis that high-frequency electrical stimulation of
      the LDTN can cause stellate ganglia damage and suppress PATs. METHODS: We
      performed long-term LDTN stimulation in 6 dogs with and 2 dogs without
      intermittent rapid LA pacing while monitoring SGNA. RESULTS: LDTN stimulation
      reduced average SGNA from 4.36 MUV (95% confidence interval [CI] 4.10-4.62 MUV)
      at baseline to 3.22 MUV (95% CI 3.04-3.40 MUV) after 2 weeks (P = .028) and
      completely suppressed all PAT episodes in all dogs studied. Tyrosine hydroxylase
      staining showed large damaged regions in both stellate ganglia, with increased
      percentages of tyrosine hydroxylase-negative cells. The terminal deoxynucleotidyl
      transferase dUTP nick end labeling assay showed that 23.36% (95% CI 18.74%
      27.98%) of ganglion cells in the left stellate ganglia and 11.15% (95% CI 9.34%
      12.96%) ganglion cells in the right stellate ganglia were positive, indicating
      extensive cell death. A reduction of both SGNA and heart rate was also observed
      in dogs with LDTN stimulation but without rapid LA pacing. Histological studies
      in the 2 dogs without intermittent rapid LA pacing confirmed the presence of
      extensive stellate ganglia damage, along with a high percentage of terminal
      deoxynucleotidyl transferase dUTP nick end labeling-positive cells. CONCLUSION:
      LDTN stimulation damages both left and right stellate ganglia, reduces left SGNA,
      and is antiarrhythmic in this canine model of PAT.

PMID- 29654855
TI  - Host-pathogen dynamics under sterilizing pathogens and fecundity-longevity trade
      off in hosts.
AB  - Infectious diseases are known to regulate population dynamics, an observation
      that underlies the use of pathogens as control agents of unwanted populations.
      Sterilizing rather than lethal pathogens are often suggested so as to avoid
      unnecessary suffering of the infected hosts. Until recently, models used to
      assess plausibility of pathogens as potential pest control agents have not
      included a possibility that reduced fecundity of the infected individuals may
      save their energy expenditure on reproduction and thus increase their longevity
      relative to the susceptible ones. Here, we develop a model of host-pathogen
      interaction that builds on this idea. We analyze the model for a variety of
      infection transmission functions, revealing that the indirect effect of
      sterilizing pathogens on mortality of the infected hosts, mediated by a fecundity
      longevity trade-off, may cause hosts at endemic equilibria to attain densities
      higher than when there is no effect of pathogens on host mortality. On the other
      hand, an opposite outcome occurs when the fecundity-longevity trade-off is
      concave or when the degree of fecundity reduction by the pathogen is high enough.
      This points to a possibility that using sterilizing pathogens as agents of pest
      control may actually be less effective than previously thought, the more so since
      we also suggest that if sexual selection acts on the host species then the
      presence of sterilizing pathogens may even enhance host densities above the
      levels achieved without infection.

PMID- 29654854
TI  - Control of clustered action potential firing in a mathematical model of
      entorhinal cortex stellate cells.
AB  - The entorhinal cortex is a crucial component of our memory and spatial navigation
      systems and is one of the first areas to be affected in dementias featuring tau
      pathology, such as Alzheimer's disease and frontotemporal dementia.
      Electrophysiological recordings from principle cells of medial entorhinal cortex
      (layer II stellate cells, mEC-SCs) demonstrate a number of key identifying
      properties including subthreshold oscillations in the theta (4-12 Hz) range and
      clustered action potential firing. These single cell properties are correlated
      with network activity such as grid firing and coupling between theta and gamma
      rhythms, suggesting they are important for spatial memory. As such, experimental
      models of dementia have revealed disruption of organised dorsoventral gradients
      in clustered action potential firing. To better understand the mechanisms
      underpinning these different dynamics, we study a conductance based model of mEC
      SCs. We demonstrate that the model, driven by extrinsic noise, can capture
      quantitative differences in clustered action potential firing patterns recorded
      from experimental models of tau pathology and healthy animals. The differential
      equation formulation of our model allows us to perform numerical bifurcation
      analyses in order to uncover the dynamic mechanisms underlying these patterns. We
      show that clustered dynamics can be understood as subcritical Hopf/homoclinic
      bursting in a fast-slow system where the slow sub-system is governed by
      activation of the persistent sodium current and inactivation of the slow A-type
      potassium current. In the full system, we demonstrate that clustered firing
      arises via flip bifurcations as conductance parameters are varied. Our model
      analyses confirm the experimentally suggested hypothesis that the breakdown of
      clustered dynamics in disease occurs via increases in AHP conductance.

PMID- 29654856
TI  - Optimization of preparation conditions for calcium pectinate with response
      surface methodology and its application for cell encapsulation.
AB  - The most notable and unique property of pectin is its ability to form gels, which
      is the foundation of its many functions and applications. To obtain the desired
      pectin hydrogel beads for tissue engineering or biological applications, the
      combined effect of the key factors of gel properties of calcium pectinate (CP)
      beads were investigated by response surface methodology (RSM). The results
      derived from RSM indicated that the model equation of average size and mechanical
      stability were significant and could be used to describe the process under a wide
      range of preparation conditions. The optimum condition for preparing variables
      were gained graphically. Moreover, the degree of methyl-esterification (DE) of
      pectin and pectin - calcium concentrates showed significant and combined effort
      on sphericity factor (SF). The mechanical stability of CP beads was significantly
      affected by the quadratic contributions of the pectin concentration, the
      interaction effects between pectin and calcium concentration, and the linear
      contribution of pectin concentration. The viability and proliferation of cells
      encapsulated in optimal CP beads demonstrated that the optimal formula results in
      better gel properties and are more suitable to cell encapsulation.

PMID- 29654857
TI  - The antiviral activity of polysaccharides and their derivatives.
AB  - Viral infectious diseases are seriously endangering human health. In the search
      for effective antiviral drugs, people have found that polysaccharides have good
      antiviral activity. As an effective and low-toxic antiviral component,
      polysaccharides have broad prospects for medicinal use and are deserved for
      further study. Herein, the antiviral activity and action mechanisms of
      polysaccharides and their various derivatives were summed up and analyzed.

PMID- 29654858
TI  - Effect of CMC addition on steady and dynamic shear rheological properties of
      binary systems of xanthan gum and guar gum.
AB  - The effect of CMC on the steady and dynamic shear rheological properties of
      binary mixtures of XG and GG was examined at different mixing ratios. All XG-GG
      CMC ternary mixtures had high shear-thinning behavior and the n value of the
      sample with 5% CMC was the smallest compared with those of other samples. A
      marked increase in K and etaa,50 values was observed for ternary mixtures at a
      lower content (5%) of CMC, indicating that the synergistic interactions of the XG
      GG binary mixture were affected by the content of CMC. The effect of temperature
      on the etaa,50 was well described by the Arrhenius equation for all samples. The
      activation energy values of all ternary gum mixtures are higher than that of
      binary gum mixture, and these values also decreased with an increase in CMC
      content from 5 to 15%. The dynamic moduli of ternary gum mixtures decreased with
      an increase in CMC content. The tan delta value of the ternary gum mixture with
      5% CMC was much lower than those of other ternary mixtures. In general, these
      results suggest that the flow and dynamic shear rheological properties of XG-GG
      binary mixtures are strongly influenced by a small addition of CMC.

PMID- 29654859
TI  - Facile preparation and dual responsive behaviors of starch-based hydrogel
      containing azo and carboxylic groups.
AB  - Starch-based hydrogel containing azo group (SHA) was prepared through radical
      cross-linking reaction among starch- and PVA-based macromonomers, acrylic acid
      (AA) and 4-acryloyoxyazobenzene (AHAB). AHAB was prepared through an acylation
      reaction between acryloyl chloride and 4-hydroxyazobenzene (p-HAB), which was
      obtained by the diazo coupling reaction between aniline and phenol. The structure
      of SHA was confirmed with Fourier transform infrared spectrometer,
      thermogravimetric analysis and UV-Visible spectroscopy. SHA displayed pH
      sensitive swelling in buffer saline. SHA film also exhibited a reversible trans
      cis-trans photoisomerization behavior when they were subjected to alternative UV
      and visible light irradiation or dark storage. The dual-responsive characteristic
      was easily to be tailored via varying the initial amount of AHAB or AA.

PMID- 29654860
TI  - Hypoglycemic activity in vitro of polysaccharides from Camellia oleifera Abel.
      seed cake.
AB  - We isolated and purified polysaccharide from the Camellia oleifera Abel. seed
      cake (CCP) and studied its hypoglycemic activity in vitro. The molecular weight
      of CCP was 4736 Da and the monosaccharide molar composition ratio was:
      Xylose:Glucuronic acid:Galactosamine:Mannose = 10.9:4.4:2.6:1.8. The CCP
      contained conjugated proteins and belonged to acidic polysaccharide, which can
      promote the consumption of the glucose in the medium by HepG2 cells within the
      range of 0.125-0.500 mg/mL. Relative consumption rate (RCR) of the glucose was
      the highest at 0.5 mg/mL, exceeded that of the metformin hydrochloride, as well
      as that of Tea Polysaccharide under the same concentration. A meaningful
      structure activity relationship (SAR) of hypoglycemia polysaccharides had
      established. This result suggests that CCP can be used as hypoglycemic medicine
      or health food.

PMID- 29654861
TI  - Hydrolysis of lactose using beta-d-galactosidase immobilized in a modified Arabic
      gum-based hydrogel for the production of lactose-free/low-lactose milk.
AB  - beta-d-galactosidase was immobilized in a modified Arabic gum-based hydrogel for
      the hydrolysis of standard lactose and lactose contained in UHT milk with the aim
      of producing lactose-free/low-lactose milk. The hydrogel was synthesized by cross
      linking the modified Arabic gum with acrylamide, using potassium persulfate as
      initiator. Fourier-transform infrared spectroscopy and scanning electron
      microscopy confirmed the formation of the hydrogel and its three-dimensional
      porous network. Swelling degrees in distilled water, drinking water, phosphate
      buffer solution at pH7.0 and acetate buffer solution at pH4.0 were 12.56 and
      17.72, 10.65 and 12.58, 8.58 and 10.71, and 6.49 and 8.16g water per g dried
      hydrogel at room temperature and 37.0+/-1.0 degrees C, respectively. The
      immobilization capacities of beta-d-galactosidase in acetate and phosphate buffer
      solutions at room temperature were 242.52+/-0.13 and 118.42+/-0.23mg enzyme per g
      dried hydrogel, respectively, after 1440min of contact. Higher enzymatic
      activities were found after immobilization in phosphate buffer solution due to
      the isoelectric point of beta-d-galactosidase. Hydrolysis of standard lactose and
      lactose contained in UHT milk was more efficient using immobilized beta-d
      galactosidase than free beta-d-galactosidase. Immobilized beta-d-galactosidase
      was applied for three cycles of hydrolysis of lactose without significantly
      losing enzymatic activity.

PMID- 29654862
TI  - Polycaprolactone/carboxymethyl chitosan nanofibrous scaffolds for bone tissue
      engineering application.
AB  - This research focused on the physical properties and cell compatibility of
      nanofibrous scaffolds based on polycaprolactone/chitosan (PCL/CTS) and
      PCL/carboxymethyl chitosan (PCL/CMC) blends for bone tissue engineering
      application. Scaffolds were fabricated by electrospinning technique. SEM images
      showed that the undesirable ultrafine and splitting fibers in PCL/CTS scaffolds
      are eliminated by replacing CTS with CMC. PCL/CMC scaffolds exposed significantly
      improved surface hydrophilicity improvement comparing to PCL/CTS ones. The water
      contact angle of PCL scaffold was reduced on the addition of 15% CMC from 123 +/-
      1 degrees  to 51 +/- 3 degrees  in high concentration of CMC scaffold. The
      average diameter of fibers in PCL/CTS 15% and PCL/CMC 15% were 439 and 356 nm,
      respectively, which demonstrated higher concentrations of CMC resulted in
      decrease fibers diameter than other blended scaffolds. FTIR spectroscopy
      confirmed the composition of PCL/CTS and PCL/CMC scaffolds. The culturing of
      human osteoblast cells (MG63) on the scaffolds showed that all scaffolds are
      biocompatible. The PCL/CMC nanofibers exhibited promoting proliferation trend,
      compared to the PCL and PCL/CTS ones, especially at maximum concentrations of
      CMC. The results demonstrate that the PCL/CMC electrospun scaffolds can be an
      excellent candidate for bone tissue engineering application.

PMID- 29654863
TI  - The structure changes of water-soluble polysaccharides in papaya during ripening.
AB  - Papaya is a fruit mainly grown in tropical and subtropical regions. The
      structural changes of polysaccharides are highly involved in the organoleptic
      property change of papaya. However, it remains unclear how the structure
      characteristics of water-soluble polysaccharides are changed during postharvest
      ripening. It is interesting to work on this topic. In this work, the dominant
      water-soluble polysaccharide in papaya was purified. It was identified to be
      alpha-(1->4)-D-galacturonan by NMR. It remained stable during postharvest
      ripening. beta-(1->4)-D-galactan was only detected in fully green papaya. Once
      the postharvest ripening initiated, this polysaccharide was rapidly degraded.
      There were no significant differences in the structure changes of water-soluble
      polysaccharides for the naturally ripening papaya and ethylene-treated papaya.
      These results extended the understanding about the relationship between
      polysaccharide structure and papaya ripening during postharvest storage.

PMID- 29654864
TI  - Mutation of conserved residues K329 and R330 on the surface of firefly
      luciferase: Effect on proteolytic degradation.
AB  - Firefly luciferase is highly susceptible to proteolytic digestion that reduces
      its half-life and leads to loss in sensitivity. Due to the protease contamination
      in most in vitro and in vivo environments, it has interest to generate some
      mutations that may lead to improved susceptibility to digestion. Some important
      conserved residues (including K206, R213, R218, K329, R330 and R337) on
      accessible and flexible regions on the surface of Photinus pyralis luciferase
      have been suggested that susceptible to trypsinolysis. In current study, two
      mutants (K329I and R330Q) are designed to investigate the impact of these
      conserved sites on the protease stability and flexibility. This study showed that
      these mutations did not cause resistance against trypsin digestion. K329I mutant
      was more susceptible to trypsin, but no difference in the digestion pattern was
      observed. This point mutation brought about structural flexibility, which
      revealed by quenching and extrinsic fluorescence. The experimental and
      theoretical studies demonstrated that R330Q mutagenesis didn't have any
      noticeable effect on the tryptic sites and flexibility. Moreover, the results of
      proteolysis experiment showed that the primary sites for trypsin digestion are
      still exposed after both mutations.

PMID- 29654865
TI  - Chemistry, biochemistry, metabolic fate and mechanism of action of 6-oxo
      cholestan-3beta,5alpha-diol (OCDO), a tumor promoter and cholesterol metabolite.
AB  - Oxygenation products of cholesterol, named oxysterols, were suspected since the
      20th century to be involved in carcinogenesis. Among the family of oxysterol
      molecules, cholesterol-5,6-epoxides (5,6-EC) retained the attention of scientists
      because they contain a putative alkylating epoxide group. However, studies failed
      into demonstrating that 5,6-EC were direct carcinogens and revealed a surprising
      chemical stability and unreactivity towards nucleophiles in standard conditions.
      Analyses of 5,6-EC metabolism in normal cells showed that they were extensively
      transformed into cholestane-3beta,5alpha,6beta-triol (CT) by the cholesterol-5,6
      epoxide hydrolase (ChEH). Studies performed in cancer cells showed that CT was
      additionally metabolized into an oxysterol identified as the 6-oxo-cholestan
      3beta,5alpha-diol (OCDO), by the 11beta-hydroxysteroid dehydrogenase of type 2
      (HSD2), the enzyme which inactivates cortisol into cortisone. Importantly, OCDO
      was shown to display tumor promoter properties in breast cancers, by binding to
      the glucocorticoid receptor, and independently of their estrogen receptor status,
      revealing the existence of a new tumorigenic pathway centered on 5,6-EC. In
      breast tumors from patients, OCDO production as well as the expression of the
      enzymes involved in the pathway producing OCDO, namely ChEH subunits and HSD2,
      were higher compared to normal tissues, and overexpression of these enzymes
      correlate with a higher risk of patient death, indicating that this onco
      metabolism is of major importance to breast cancer pathology. Herein, we will
      review the actual knowledge and the future trends in OCDO chemistry,
      biochemistry, metabolism and mechanism of action and will discuss the impact of
      OCDO discovery on new anticancer therapeutic strategies.

PMID- 29654866
TI  - Effects of the beta2 agonist formoterol on atrophy signaling, autophagy, and
      muscle phenotype in respiratory and limb muscles of rats with cancer-induced
      cachexia.
AB  - Muscle mass loss and wasting are characteristic features of patients with chronic
      conditions including cancer. Beta-adrenoceptors attenuate muscle wasting. We
      hypothesized that specific muscle atrophy signaling pathways and altered
      metabolism may be attenuated in cancer cachectic animals receiving treatment with
      the beta2 agonist formoterol. In diaphragm and gastrocnemius of tumor-bearing
      rats (intraperitoneal inoculum, 108 AH-130 Yoshida ascites hepatoma cells, 7-day
      study period) with and without treatment with formoterol (0.3 mg/kg body
      weight/day/7days, subcutaneous), atrophy signaling pathways (NF-kappaB, MAPK,
      FoxO), proteolytic markers (ligases, proteasome, ubiquitination), autophagy
      markers (p62, beclin-1, LC3), myostatin, apoptosis, muscle metabolism markers,
      and muscle structure features were analyzed (immunoblotting,
      immunohistochemistry). In diaphragm and gastrocnemius of cancer cachectic rats,
      fiber sizes were reduced, levels of structural alterations, atrophy signaling
      pathways, proteasome content, protein ubiquitination, autophagy, and myostatin
      were increased, while those of regenerative and metabolic markers (myoD, mTOR,
      AKT, and PGC-1alpha) were decreased. Formoterol treatment attenuated such
      alterations in both muscles. Muscle wasting in this rat model of cancer-induced
      cachexia was characterized by induction of significant structural alterations,
      atrophy signaling pathways, proteasome activity, apoptotic and autophagy markers,
      and myostatin, along with a significant decline in the expression of muscle
      regenerative and metabolic markers. Treatment of the cachectic rats with
      formoterol partly attenuated the structural alterations and atrophy signaling,
      while improving other molecular perturbations similarly in both respiratory and
      limb muscles. The results reported in this study have relevant therapeutic
      implications as they showed beneficial effects of the beta2 agonist formoterol in
      the cachectic muscles through several key biological pathways.

PMID- 29654867
TI  - Preclinical evaluation of the neutralizing ability of a monospecific antivenom
      for the treatment of envenomings by Bothrops lanceolatus in Martinique.
AB  - Bothrops lanceolatus is an endemic viperid species in the Lesser Caribbean island
      of Martinique. Envenomings by this species are characterized by local and
      systemic effects, among which the development of thrombosis in various organs is
      the most severe complication. An experimental toxicological characterization of
      this venom was performed using in vivo mouse tests and various in vitro assays.
      The venom induced lethal, local and systemic hemorrhagic, edema-forming,
      myotoxic, thrombocytopenic, proteinase and phospholipase A2 activities. The
      preclinical efficacy of a batch of monospecific Bothrofav(r) antivenom currently
      in use in Martinique was assessed. The antivenom was highly effective in the
      neutralization of all activities tested, in agreement with its described clinical
      efficacy. This batch of antivenom showed a higher preclinical efficacy as
      compared to a previous batch used in the past.

PMID- 29654868
TI  - Bee venom therapy: Potential mechanisms and therapeutic applications.
AB  - Bee venom is a very complex mixture of natural products extracted from honey bee
      which contains various pharmaceutical properties such as peptides, enzymes,
      biologically active amines and nonpeptide components. The use of bee venom into
      the specific points is so called bee venom therapy, which is widely used as a
      complementary and alternative therapy for 3000 years. A growing number of
      evidence has demonstrated the anti-inflammation, the anti-apoptosis, the anti
      fibrosis and the anti-arthrosclerosis effects of bee venom therapy. With these
      pharmaceutical characteristics, bee venom therapy has also been used as the
      therapeutic method in treating rheumatoid arthritis, amyotrophic lateral
      sclerosis, Parkinson's disease, Alzheimer's disease, liver fibrosis,
      atherosclerosis, pain and others. Although widely used, several cases still
      reported that bee venom therapy might cause some adverse effects, such as local
      itching or swelling. In this review, we summarize its potential mechanisms,
      therapeutic applications, and discuss its existing problems.

PMID- 29654869
TI  - A membrane disrupting toxin from wasp venom underlies the molecular mechanism of
      tissue damage.
AB  - The molecular mechanism of the local hypersensitivity reactions to wasp venom
      including dermal necrosis remains an enigma regardless of the numerosity of the
      reported cases. In this study, we discovered a new membrane disrupting toxin,
      VESCP-M2 responsible for tissue damage symptoms following Vespa mandarinia
      envenomation. Electrophysiological assays revealed a potent ability of VESCP-M2
      to permeate the cell membrane whereas in vivo experiments demonstrated that VESCP
      M2 induces edema, pain and dermal necrosis characterized by the presence of
      morphological and behavioral phenotypes, pro-inflammatory mediators, biomarkers
      as well as the disruption of dermal tissue. This study presents the molecular
      mechanism and symptom-related function of VESCP-M2 which may form a basis for
      prognosis as well as therapeutic interventions.

PMID- 29654870
TI  - A functional and thromboelastometric-based micromethod for assessing crotoxin
      anticoagulant activity and antiserum relative potency against Crotalus durissus
      terrificus venom.
AB  - The assessment of the capacity of antivenoms to neutralize the lethal activity of
      snake venoms still relies on traditional rodent in vivo lethality assay. ED50 and
      LD50 assays require large quantities of venoms and antivenoms, and besides
      leading to animal suffering. Therefore, in vitro tests should be introduced for
      assessing antivenom neutralizing capacity in intermediary steps of antivenom
      production. This task is facilitated when one key lethal toxin is identified. A
      good example is crotoxin, a beta-neurotoxin phospholipase A2-like toxin that
      presents anticoagulant activity in vitro and is responsible for the lethality of
      venoms of Crotalus durissus snakes. By using rotational thromboelastometry, we
      reported recently one sensitive coagulation assay for assessing relative potency
      of the anti-bothropic serum in neutralizing procoagulant activity of Bothrops
      jararaca venom upon recalcified factor-XII-deficient chicken plasma samples
      (CPS). In this study, we stablished conditions for determining relative potency
      of four batches of the anti-crotalic serum (ACS) (antagonist) in inactivating
      crotoxin anticoagulant activity in CPS (target) simultaneously treated with one
      classical activator of coagulation (agonists). The correlation coefficient (r)
      between values related the ACS potency in inactivating both in vitro crotoxin
      anticoagulant activity and the in vivo lethality of whole venom (ED50) was 0.94
      (p value < 0.05). In conclusion, slowness in spontaneous thrombin/fibrin
      generation even after recalcification elicit time lapse sufficient for
      elaboration of one dose-response curve to pro- or anti-coagulant agonists in CPS.
      We propose this methodology as an alternative and sensitive assay for assessing
      antivenom neutralizing ability in plasma of immunized horses as well as for in
      process quality control.

PMID- 29654871
TI  - Carbapenem-resistant Enterobacteriaceae in wildlife, food-producing, and
      companion animals: a systematic review.
AB  - OBJECTIVES: The spread of carbapenem-resistant Enterobacteriaceae (CRE) in
      healthcare settings challenges clinicians worldwide. However, little is known
      about dissemination of CRE in livestock, food, and companion animals and
      potential transmission to humans. METHODS: We performed a systematic review of
      all studies published in the PubMed database between 1980 and 2017 and included
      those reporting the occurrence of CRE in samples from food-producing and
      companion animals, wildlife, and exposed humans. The primary outcome was the
      occurrence of CRE in samples from these animals; secondary outcomes included the
      prevalence of CRE, carbapenemase types, CRE genotypes, and antimicrobial
      susceptibilities. RESULTS: We identified 68 articles describing CRE among pigs,
      poultry, cattle, seafood, dogs, cats, horses, pet birds, swallows, wild boars,
      wild stork, gulls, and black kites in Africa, America, Asia, Australia, and
      Europe. The following carbapenemases have been detected (predominantly affecting
      the genera Escherichia and Klebsiella): VIM, KPC, NDM, OXA, and IMP. Two studies
      found that 33-67% of exposed humans on poultry farms carried carbapenemase
      producing CRE closely related to isolates from the farm environment. Twenty-seven
      studies selectively screened samples for CRE and found a prevalence of <1% among
      livestock and companion animals in Europe, 2-26% in Africa, and 1-15% in Asia.
      Wildlife (gulls) in Australia and Europe carried CRE in 16-19%. CONCLUSIONS: The
      occurrence of CRE in livestock, seafood, wildlife, pets, and directly exposed
      humans poses a risk for public health. Prospective prevalence studies using
      molecular and cultural microbiological methods are needed to better define the
      scope and transmission of CRE.

PMID- 29654872
TI  - Pyelonephritis in persons after age 50 as a clinical marker of urogenital cancer.
AB  - OBJECTIVES: Urinary tract infections have been linked with urinary tract cancer,
      but the association remains controversial. We examined whether pyelonephritis is
      a clinical marker of urogenital cancer. METHODS: We used Danish medical databases
      to create a population-based cohort of patients with an incident hospital-based
      pyelonephritis diagnosis during 1994-2013. Follow-up for cancer began at
      pyelonephritis diagnosis and ended on 30 November 2013. We restricted the cohort
      to patients older than 50 years, as urogenital cancer risk in the younger
      population is low. We calculated the absolute risk of urogenital cancer and the
      standardized incidence ratio (SIR) comparing risk observed in pyelonephritis
      patients to risk expected in the general population of Denmark. RESULTS: Among 15
      070 patients with pyelonephritis, we observed 197 urinary tract cancers and 374
      genital organ cancers over a 20-year follow-up period. The absolute risk of
      urogenital cancer was 1.5% 6 months after a pyelonephritis diagnosis, and the
      cumulative risk was 3.0% at 5 years. During the first 6 months following a
      pyelonephritis diagnosis, the SIR of urogenital cancer was 8.56 (95% CI 7.49
      9.75). Between 6 and 12 months following this diagnosis, the SIR was 1.75 (95% CI
      1.26-2.35), and beyond 1 year the SIR was approximately unity for most cancers.
      Notably, the SIR for bladder cancer among women remained elevated beyond 1 year
      of follow-up. CONCLUSIONS: Patients presenting with a hospital-based diagnosis of
      pyelonephritis had a higher 6-month risk of urogenital cancer than expected.
      However, causation cannot be inferred because of the study design.

PMID- 29654873
TI  - 'Aspergillus galactomannan detection in exhaled breath condensate compared to
      bronchoalveolar lavage fluid' by Husain, et al.

PMID- 29654874
TI  - Warnings and caveats in brain controllability.
AB  - A recent article by Gu et al. (Nat. Commun. 6, 2015) proposed to characterize
      brain networks, quantified using anatomical diffusion imaging, in terms of their
      "controllability", drawing on concepts and methods of control theory. They
      reported that brain activity is controllable from a single node, and that the
      topology of brain networks provides an explanation for the types of control roles
      that different regions play in the brain. In this work, we first briefly review
      the framework of control theory applied to complex networks. We then show
      contrasting results on brain controllability through the analysis of five
      different datasets and numerical simulations. We find that brain networks are not
      controllable (in a statistical significant way) by one single region.
      Additionally, we show that random null models, with no biological resemblance to
      brain network architecture, produce the same type of relationship observed by Gu
      et al. between the average/modal controllability and weighted degree. Finally, we
      find that resting state networks defined with fMRI cannot be attributed specific
      control roles. In summary, our study highlights some warning and caveats in the
      brain controllability framework.

PMID- 29654876
TI  - Multi-voxel pattern classification differentiates personally experienced event
      memories from secondhand event knowledge.
AB  - Studies of autobiographical memory retrieval often use photographs to probe
      participants' memories for past events. Recent neuroimaging work has shown that
      viewing photographs depicting events from one's own life evokes a characteristic
      pattern of brain activity across a network of frontal, parietal, and medial
      temporal lobe regions that can be readily distinguished from brain activity
      associated with viewing photographs from someone else's life (Rissman, Chow,
      Reggente, and Wagner, 2016). However, it is unclear whether the neural signatures
      associated with remembering a personally experienced event are distinct from
      those associated with recognizing previously encountered photographs of an event.
      The present experiment used a novel functional magnetic resonance imaging (fMRI)
      paradigm to investigate putative differences in brain activity patterns
      associated with these distinct expressions of memory retrieval. Eighteen
      participants wore necklace-mounted digital cameras to capture events from their
      everyday lives over the course of three weeks. One week later, participants
      underwent fMRI scanning, where on each trial they viewed a sequence of
      photographs depicting either an event from their own life or from another
      participant's life and judged their memory for this event. Importantly, half of
      the trials featured photographic sequences that had been shown to participants
      during a laboratory session administered the previous day. Multi-voxel pattern
      analyses assessed the sensitivity of two brain networks of interest-as identified
      by a meta-analysis of prior autobiographical and laboratory-based memory
      retrieval studies-to the original source of the photographs (own life or other's
      life) and their experiential history as stimuli (previewed or non-previewed). The
      classification analyses revealed a striking dissociation: activity patterns
      within the autobiographical memory network were significantly more diagnostic
      than those within the laboratory-based network as to whether photographs depicted
      one's own personal experience (regardless of whether they had been previously
      seen), whereas activity patterns within the laboratory-based memory network were
      significantly more diagnostic than those within the autobiographical memory
      network as to whether photographs had been previewed (regardless of whether they
      were from the participant's own life). These results, also apparent in whole
      brain searchlight classifications, provide evidence for dissociable patterns of
      activation across two putative memory networks as a function of whether real
      world photographs trigger the retrieval of firsthand experiences or secondhand
      event knowledge.

PMID- 29654875
TI  - Maternal Interleukin-6 concentration during pregnancy is associated with
      variation in frontolimbic white matter and cognitive development in early life.
AB  - Maternal inflammation during pregnancy can alter the trajectory of fetal brain
      development and increase risk for offspring psychiatric disorders. However, the
      majority of relevant research to date has been conducted in animal models. Here,
      in humans, we focus on the structural connectivity of frontolimbic circuitry as
      it is both critical for socioemotional and cognitive development, and commonly
      altered in a range of psychiatric disorders associated with intrauterine
      inflammation. Specifically, we test the hypothesis that elevated maternal
      concentration of the proinflammatory cytokine interleukin-6 (IL-6) during
      pregnancy will be associated with variation in microstructural properties of this
      circuitry in the neonatal period and across the first year of life. Pregnant
      mothers were recruited in early pregnancy and maternal blood samples were
      obtained for assessment of maternal IL-6 concentrations in early (12.6 +/- 2.8
      weeks [S.D.]), mid (20.4 +/- 1.5 weeks [S.D.]) and late (30.3 +/- 1.3 weeks
      [S.D.]) gestation. Offspring brain MRI scans were acquired shortly after birth (N
      = 86, scan age = 3.7 +/- 1.7 weeks [S.D.]) and again at 12-mo age (N = 32, scan
      age = 54.0 +/- 3.1 weeks [S.D.]). Diffusion Tensor Imaging (DTI) was used to
      characterize fractional anisotropy (FA) along the left and right uncinate
      fasciculus (UF), representing the main frontolimbic fiber tract. In N = 30 of the
      infants with serial MRI data at birth and 12-mo age, cognitive and socioemotional
      developmental status was characterized using the Bayley Scales of Infant
      Development. All analyses tested for potentially confounding influences of
      household income, prepregnancy Body-Mass-Index, obstetric risk, smoking during
      pregnancy, and infant sex, and outcomes at 12-mo age were additionally adjusted
      for the quality of the postnatal caregiving environment. Maternal IL-6
      concentration (averaged across pregnancy) was prospectively and inversely
      associated with FA (suggestive of reduced integrity under high inflammatory
      conditions) in the newborn offspring (bi-lateral, p < 0.01) in the central
      portion of the UF proximal to the amygdala. Furthermore, maternal IL-6
      concentration was positively associated with rate of FA increase across the first
      year of life (bi-lateral, p < 0.05), resulting in a null association between
      maternal IL-6 and UF FA at 12-mo age. Maternal IL-6 was also inversely associated
      with offspring cognition at 12-mo age, and this association was mediated by FA
      growth across the first year of postnatal life. Findings from the current study
      support the premise that susceptibility for cognitive impairment and potentially
      psychiatric disorders may be affected in utero, and that maternal inflammation
      may constitute an intrauterine condition of particular importance in this
      context.

PMID- 29654878
TI  - Inter-subject phase synchronization for exploratory analysis of task-fMRI.
AB  - Analysis of task-based fMRI data is conventionally carried out using a hypothesis
      driven approach, where blood-oxygen-level dependent (BOLD) time courses are
      correlated with a hypothesized temporal structure. In some experimental designs,
      this temporal structure can be difficult to define. In other cases, experimenters
      may wish to take a more exploratory, data-driven approach to detecting task
      driven BOLD activity. In this study, we demonstrate the efficiency and power of
      an inter-subject synchronization approach for exploratory analysis of task-based
      fMRI data. Combining the tools of instantaneous phase synchronization and
      independent component analysis, we characterize whole-brain task-driven responses
      in terms of group-wise similarity in temporal signal dynamics of brain networks.
      We applied this framework to fMRI data collected during performance of a simple
      motor task and a social cognitive task. Analyses using an inter-subject phase
      synchronization approach revealed a large number of brain networks that
      dynamically synchronized to various features of the task, often not predicted by
      the hypothesized temporal structure of the task. We suggest that this
      methodological framework, along with readily available tools in the fMRI
      community, provides a powerful exploratory, data-driven approach for analysis of
      task-driven BOLD activity.

PMID- 29654877
TI  - Enhanced perceptual processing of self-generated motion: Evidence from steady
      state visual evoked potentials.
AB  - The sense of agency emerges when our voluntary actions produce anticipated or
      predictable outcomes in the external world. It remains unclear how the sense of
      control also influences our perception of the external world. The present study
      examined perceptual processing of self-generated motion versus non-self-generated
      motion using steady-state visual evoked potentials (SSVEPs). Participants
      continuously moved their finger on a touchpad to trigger the movements of two
      shapes (Experiment 1) or two groups of dots (Experiment 2) on a monitor. Degree
      of control was manipulated by varying the spatial relation between finger
      movement and stimulus trajectory across conditions. However, the velocity, onset
      time, and offset time of visual stimuli always corresponded to participants'
      finger movement. Stimuli flickered at a frequency of either 7.5 Hz or 10 Hz, thus
      SSVEPs of these frequencies and their harmonics provided a frequency-tagged
      measurement of perceptual processing. Participants triggered the motion of all
      stimuli simultaneously, but had greater levels of control over some stimuli than
      over others. Their task was to detect a brief colour change on the border(s) of
      one shape (Experiment 1) or of one group of dots (Experiment 2). Although control
      over shapes/dots was irrelevant to the visual detection task, we found stronger
      SSVEPs for stimuli that were under a high level of control, compared with the
      stimuli that were under a low level of control. Our results suggest that the
      spatial regularity between self-generated movements and visual input boosted the
      neural responses underlying perceptual processing. Our results support the
      preactivation account of sensory attenuation, suggesting that perceptual
      processing of self-generated events is enhanced rather than inhibited.

PMID- 29654879
TI  - Anti-oxidant effect of bergamot polyphenolic fraction counteracts doxorubicin
      induced cardiomyopathy: Role of autophagy and c-kitposCD45negCD31neg cardiac stem
      cell activation.
AB  - Doxorubicin (DOXO) is one of the most widely used antineoplastic drugs. Despite
      its highly beneficial effects against several malignancies, the clinical use of
      DOXO is often associated to cardiomyopathy that leads to congestive heart
      failure. Here we investigated the antioxidant and cardioprotective effects of a
      polyphenol-rich fraction of citrus bergamot (BPF), in DOXO-induced cardiac damage
      in rats. Moreover, we evaluated the effect of BPF on cardiomyocyte survival and
      resident endogenous cardiac stem/progenitor cell (eCSC) activation. Adult male
      Wistar rats were i.p. injected with saline (serving as controls, CTRL, n = 10),
      BPF (20 mg/kg daily for 14 consecutive days, n = 10), DOXO (6 doses of 2,5 mg/Kg
      from day 1 to day 14, n = 10), and DOXO + BPF (n = 10). Animals were then
      sacrificed 7 days later (i.e., at 21 days). DOXO administration reduced cardiac
      function at 21 days, an adverse effect significantly attenuated in animals
      receiving DOXO + BPF. No changes were detected in rats receiving just saline or
      BPF alone. The cardioprotective effect of BPF on DOXO acute toxicity was also
      associated with a significant antioxidant effect coupled with protective
      autophagy restoration, and attenuation of cardiomyocyte apoptosis and reactive
      hypertrophy. Finally, treatment of rats with BPF prevented eCSCs attrition by
      DOXO which was followed by a limited but significant increase of newly-formed
      BrdU+ cardiomyocytes. In conclusion, BPF reduces DOXO-induced cardiotoxicity by
      counteracting reactive oxygen species (ROS) overproduction, thereby restoring
      protective autophagy and attenuating cardiomyocyte apoptosis and pathologic
      remodeling. This beneficial effects on the early toxicity of DOXO is associated
      with enhanced CSCs survival and regenerative potential. Overall these data point
      to a potential clinical role by diet supplementation with polyphenol-rich
      fraction of citrus bergamot in counteracting antracycline-induced cardiomyopathy.

PMID- 29654880
TI  - Neural/Bayes network predictor for inheritable cardiac disease pathogenicity and
      phenotype.
AB  - The cardiac muscle sarcomere contains multiple proteins contributing to
      contraction energy transduction and its regulation during a heartbeat.
      Inheritable heart disease mutants affect most of them but none more frequently
      than the ventricular myosin motor and cardiac myosin binding protein c (mybpc3).
      These co-localizing proteins have mybpc3 playing a regulatory role to the energy
      transducing motor. Residue substitution and functional domain assignment of each
      mutation in the protein sequence decides, under the direction of a sensible
      disease model, phenotype and pathogenicity. The unknown model mechanism is
      decided here using a method combing neural and Bayes networks. Missense single
      nucleotide polymorphisms (SNPs) are clues for the disease mechanism summarized in
      an extensive database collecting mutant sequence location and residue
      substitution as independent variables that imply the dependent disease phenotype
      and pathogenicity characteristics in 4 dimensional data points (4ddps). The SNP
      database contains entries with the majority having one or both dependent data
      entries unfulfilled. A neural network relating causes (mutant residue location
      and substitution) and effects (phenotype and pathogenicity) is trained,
      validated, and optimized using fulfilled 4ddps. It then predicts unfulfilled
      4ddps providing the implicit disease model. A discrete Bayes network interprets
      fulfilled and predicted 4ddps with conditional probabilities for phenotype and
      pathogenicity given mutation location and residue substitution thus relating the
      neural network implicit model to explicit features of the motor and mybpc3
      sequence and structural domains. Neural/Bayes network forecasting automates
      disease mechanism modeling by leveraging the world wide human missense SNP
      database that is in place and expanding.

PMID- 29654882
TI  - Neuroticism is linked to microstructural left-right asymmetry of fronto-limbic
      fibre tracts in adolescents with opposite effects in boys and girls.
AB  - Neuroticism is a fundamental personality trait that reflects a tendency to
      experience heightened negative affect and susceptibility to stress. Negative
      emotionality has been associated with fronto-limbic brain structures and
      connecting fibre tracts. The major fibre tracts connecting the frontal and limbic
      brain regions are the cingulum bundle and uncinate fasciculus. We previously
      found that healthy adults with higher neuroticism scores had decreased left
      relative to right fractional anisotropy (FA) of the cingulum. Both cingulum and
      uncinate fasciculus FA increases throughout childhood and into early adulthood.
      Since adolescence is associated with an increased incidence of anxiety and mood
      disorders, for which neuroticism is a known risk factor, the question arises
      whether the association between neuroticism and fronto-limbic white matter
      microstructure asymmetry is already present in children and adolescents or
      whether such relationship emerges during this age period. To address this
      question, we assessed 72 typically-developing 10-to-15 year-olds with diffusion
      weighted imaging on a 3 T magnetic resonance scanner. Neuroticism was assessed
      with the Junior Eysenck Personality Questionnaire. FA and parallel and
      perpendicular diffusivity measures were extracted for cingulum, uncinate
      fasciculus as well as the white matter underlying the ventromedial prefrontal
      cortex. Higher neuroticism scores were associated with decreased left relative to
      right cingulum FA in boys, while in girls, higher neuroticism scores were
      associated with increased left relative to right cingulum and ventromedial
      prefrontal white matter FA, indicating that there are sex differences in the
      neural correlates of neuroticism. Our findings suggest that the link between
      neuroticism and frontal-limbic white matter microstructure asymmetry likely
      predates early adolescence. Future studies need to elucidate the significance of
      the observed sex differences in the neural correlates of neuroticism.

PMID- 29654883
TI  - Long-term retention of proprioceptive recalibration.
AB  - Sensorimotor changes are well documented following reaches with altered visual
      feedback of the hand. Specifically, reaches are adapted and proprioceptive
      estimates of felt hand position shifted in the direction of the visual feedback
      experienced. While research has examined one's ability to retain reach
      adaptation, limited attention has been given to the retention of proprioceptive
      recalibration. This experiment examined retention of proprioceptive recalibration
      in the form of recall and savings (i.e., faster proprioceptive recalibration on
      subsequent testing days) over an extended period of time (i.e., four days). As
      well, we looked to determine the benefits of additional training on short-term
      retention (i.e., one day) of proprioceptive recalibration. Twenty-four
      participants trained to reach to a visual target while seeing a cursor that was
      rotated 30 degrees  clockwise relative to their hand on an initial day of
      testing. Half of the participants then completed additional reach training trials
      on 4 subsequent testing days (Training group), whereas the second half of
      participants did not complete additional training until Day 5 (Non-Training
      group). Participants provided estimates of their felt hand position on all 5
      testing days to establish retention of proprioceptive recalibration. Results
      revealed that proprioceptive recalibration was recalled 24 h after initial
      training across all participants. Recall of proprioceptive recalibration was not
      observed on subsequent testing days for the Non-Training group, while recall of
      proprioceptive recalibration was retained at a similar level across all
      subsequent testing days for the Training group. Retention of proprioceptive
      recalibration in the form of savings was observed on Day 5 in the Non-Training
      group. These results reveal that short-term recall of proprioceptive
      recalibration does not benefit from additional training. Moreover, the different
      time scales (i.e., retention in the form of recall seen only at 24 h after
      initial training versus savings observed 4 days after initial training in the Non
      Training group), suggest that distinct processes may underlie recall and savings
      of proprioceptive recalibration.

PMID- 29654884
TI  - Anti-fibrotic treatments: A review of clinical evidence.
AB  - Renal fibrosis is a condition characterized by excessive extracellular matrix
      accumulation in the kidney. Representing the final common result of a variety of
      injuries, it can lead to chronic kidney disease and end-stage renal disease.
      Although major efforts have been made in understanding the process of renal
      fibrosis, attempts to halt its progression have been successful only in a
      laboratory setting with limited success in clinical practice. Here, we review the
      current knowledge on the process of renal fibrogenesis and the emerging anti
      fibrotic drugs that have shown encouraging results in experimental models and
      were subsequently tested in clinical trials. We also propose possible
      explanations that may account for clinical trial failures and poor translation
      outcomes. Finally, we discuss alternative therapeutic options and future
      directions in which anti-fibrotic treatments may be coupled with drugs that can
      enhance endogenous tissue regeneration.

PMID- 29654881
TI  - A systematic literature review of sex differences in childhood language and brain
      development.
AB  - The extent of sex differences in childhood language development is unclear. We
      conducted a systematic literature review synthesizing results from studies
      examining sex differences in brain structure and function relevant to language
      development during childhood. We searched PubMed and Scopus databases, and this
      returned a total of 46 published studies meeting criteria for inclusion that
      directly examined sex differences in brain development relevant to language
      function in children. The results indicate that: (a) sex differences in brain
      structure or function do not necessarily lead to differences in language task
      performance; (b) evidence for sex differences in brain and language development
      are limited; (c) when present, sex differences often interact with a variety of
      factors such as age and task. Overall, the magnitude of sexual dimorphism of
      brain developmental trajectories associated with language is not as significant
      as previously thought. Sex differences were found, however, in studies employing
      tighter age ranges. This suggests that sex differences may be more prominent
      during certain developmental stages but are negligible in other stages, likely
      due to different rates of maturation between the sexes. More research is needed
      to improve our understanding of how sex differences may arise due to the
      influence of sex hormones and developmental stages, and how these differences may
      lead to differences in various language task performance. These studies are
      expected to provide normative information that may be used in studies examining
      neurodevelopmental disorders that frequently affect more males than females, and
      also often affect language development.

PMID- 29654885
TI  - Fabrication of inhaled hybrid silver/ciprofloxacin nanoparticles with synergetic
      effect against Pseudomonas aeruginosa.
AB  - Ciprofloxacin (CFX) is a fluoroquinolone antibiotic used as a first line
      treatment against infections caused by Pseudomonas aeruginosa and Streptococcus
      pneumonia that are commonly acquired by cystic fibrosis (CF) patients. However,
      no inhalation formulation is currently available for ciprofloxacin. Hybrid silica
      coated silver nanoparticles were prepared using Stober reaction and the optimum
      ratio of chitosan and sodium tripolyphosphate was used to encapsulate CFX.
      Particle deposition was assessed in vitro using twin stage impinger while
      antimicrobial activity was evaluated based on the planktonic growth of P.
      aeruginosa as well as against P. aeruginosa sp biofilm formation. In vitro
      deposition results showed significant deposition in stage 2 using twin stage
      impinger (TSI) (~70%). Compared to CFX, the formed hybrid nanoparticles were 3-4
      folds more effective against inhibiting growth and biofilm formation by P.
      aeruginosa PAO1 and P. aeruginosa NCTC 10662.

PMID- 29654886
TI  - Role of ABC transporters White, Scarlet and Brown in brown planthopper eye
      pigmentation.
AB  - The brown planthopper ATP-binding cassette (ABC) proteins White (W), Scarlet (St)
      and Brown (Bw) belong to the ABC transporter superfamily and are responsible for
      the transportation of guanine and tryptophan precursors of eye pigments. In the
      present study, the brown planthopper White (NlW), S t(NlSt) and Bw (NlBw) genes
      were cloned, and subsequent phylogenetic analysis showed that these genes are
      clustered with their respective homologues, with a genetic relationship observed
      between NlW and its Bemisia tabaci homologue having the highest similarity.
      Sequence alignments showed that these three proteins have a highly conserved
      Walker A domain, an ABC "signature sequence" and a Walker B domain. QRT-PCR
      demonstrated that W, St and Bw are highly expressed in the head of long-winged
      males and are highly expressed in both egg and male. Adult eye colour was altered
      after the downregulation of NlW, NlSt and NlBw in the 1st to 3rd instar nymph.
      The eye colours of emerged adults became white, dark and red after injection of
      dsNlW, dsNlSt and dsNlBw, respectively. The eye pigment content assay revealed
      that xanthommatin and pteridine were significantly decreased after the injection
      of dsRNAs, and the range of variation was inversely correlated with nymph age.
      The present study provides a theoretical basis for understanding the function of
      ABC transporters at the molecular and biochemical levels.

PMID- 29654887
TI  - Emerging role of dynamic RNA modifications during animal development.
AB  - The central dogma of molecular biology statically says that the information flows
      from DNA to messenger RNA to protein. But the recent advances in mass
      spectrometry and high throughput technology have helped the scientists to view
      RNA as little more than a courier of genetic information encoded in the DNA. The
      dynamics of RNA modifications in coding and non-coding RNAs are just emerging as
      a carrier of non-genetic information, uncovering a new layer of complexity in the
      regulation of gene expression and protein translation. In this review, we
      summarize about the current knowledge of N6-methyladenosine (m6A), N1
      methyladenosine (m1A), 5-methylcytosine (m5C) and pseudouridine (Psi)
      modifications in RNA, and described how these RNA modifications are implicated in
      early animal development and in several human diseases.

PMID- 29654888
TI  - Towards the structural characterization of the human methyltransferome.
AB  - Approximately 2000 structures of methyltransferases (MTases) are currently
      available, displaying fifteen different folds for binding a methyl donor and
      providing molecular level insight into nearly half the human methyltransferome.
      Several MTases involved in gene expression and regulation are catalytically
      inefficient when isolated, and their catalytic domains often show inhibitory
      active site architectures. Recently reported structures of complexes that more
      closely reflect biological context have begun to reveal the structural basis of
      activation. DNA and particular histone MTases are allosterically activated by
      binding histone modifications using reader domains or separate reader proteins,
      and some MTases operating beyond chromatin are activated by binding an activator
      protein. In this review, we describe the structural status of the human
      methyltransferome and then discuss newly revealed structural mechanisms of MTase
      activation.

PMID- 29654889
TI  - HOXB9 acetylation at K27 is responsible for its suppression of colon cancer
      progression.
AB  - We previously reported that HOXB9 is overexpressed in colon cancer and predicts a
      favourable patient outcome, which is opposite to the tumour-promoting role of
      HOXB9 in other cancers. We hypothesized that HOXB9 acetylation may account for
      its inhibitory role in colon cancer. We aim to examine the role of acetylated
      HOXB9 in colon cancer cells and patients. The AcK27-HOXB9 levels in colon cancer
      cells and patients were analysed by Western blot analysis and
      immunohistochemistry separately. Correlation between AcK27-HOXB9 expression and
      patient survival was assessed by Kaplan-Meier analysis. HOXB9 target gene EZH2
      was determined by luciferase assay in HOXB9-transfected colon cancer cells.
      Nucleocytoplasmic translocation of HOXB9 was detected by subcellular
      fractionation and immunofluorescence. The AcK27-HOXB9 level was decreased in
      colon cancer patients and predicted better outcome. HOXB9 upregulated oncogenic
      EZH2 expression, whereas AcK27-HOXB9 suppressed it by translocating HOXB9 from
      nuclei into cytoplasm. We demonstrated that AcK27-HOXB9 inhibits while non
      acetylated HOXB9 promotes EZH2 expression and colon cancer progression. Thus,
      AcK27-HOXB9 underlies the tumour suppressive role of HOXB9. Detection of the
      ratio between AcK27-HOXB9 and HOXB9 is of differential diagnostic value for colon
      cancer patients.

PMID- 29654890
TI  - Residential radon and small cell lung cancer. A systematic review.
AB  - Residential radon exposure is considered the second cause of lung cancer and the
      first in never smokers. Nevertheless, the association between the different
      histological types of lung cancer and radon is not completely clear, and radon
      effect on small cell lung cancer is not completely understood. We aim to asses
      the effect of residential radon exposure on the risk of small cell lung cancer
      (SCLC) in general population and miners through a systematic review applying
      predefined inclusion and exclusion criteria. 16 studies were included. Most of
      them point to a relationship between indoor radon and SCLC, though some
      investigations show no association. When comparing the risk of SCLC due to radon
      exposure with NSCLC, it can be observed that an increased risk for SCLC is
      present. Small cell lung cancer seems to be the histological type of lung cancer
      most tightly related with residential radon.

PMID- 29654891
TI  - Emerging roles of Hippo signaling in inflammation and YAP-driven tumor immunity.
AB  - Initially identified as a cell and organ size controller, Hippo pathway turns
      into a hotspot for researchers. Within recent years, more and more mechanisms
      about Hippo pathway were uncovered. Even though Hippo signaling has been revealed
      to exert controversial roles according to different cell context and
      microenvironment, which is because of its diversified interplays with a great
      variety of signaling transduction cascades; mechanisms other than size
      limitation, however, remain to be elucidated. Recently, a growing number of
      studies tend to put Hippo on inflammatory and immunological focus: its
      antimicrobial role in flies, its pro- or anti-inflammation in mammals, as well as
      its relevance to cancerous immunity. From inflammation to tumor immunogenicity,
      Hippo has been gradually justified to play a crucial role. This review summarized
      the latest findings regarding the involvement of Hippo pathway in immunity, and a
      more comprehensive understanding of Hippo pathway will shed light on clinical
      translational potential even precision medicine.

PMID- 29654892
TI  - Hospital outbreak due to a Klebsiella pneumoniae ST147 clonal strain co-producing
      KPC-2 and VIM-1 carbapenemases in a tertiary teaching hospital in Northern
      Greece.
AB  - Here we present the characteristics of a large outbreak caused by a clonal
      Klebsiella pneumoniae strain producing both KPC-2 and VIM-1 carbapenemases in a
      tertiary teaching hospital. Between January 2013 and January 2015, 45 carbapenem
      resistant K. pneumoniae isolates that gave a positive modified Hodge test and
      were phenotypically suspected of metallo-beta-lactamase (MBL) and K. pneumoniae
      carbapenemase (KPC) co-production were recovered from 25 patients hospitalised in
      AHEPA University Hospital (Thessaloniki, Greece). All of the patients were
      hospitalised in the three intensive care units of the hospital and 17 (68%) of
      them developed bloodstream infections; the overall mortality of the patients
      involved in the outbreak was 48% (12/25). Molecular testing verified that all 45
      K. pneumoniae isolates co-harboured blaKPC-2 and blaVIM-1 genes and were
      associated with OmpK35 deficiency and OmpK36 porin loss. The blaTEM-1 gene was
      also present in 18 isolates. Pulsed-field gel electrophoresis (PFGE) clustered
      all of the isolates into a single clonal type, and multilocus sequence typing
      (MLST) assigned them to the emerging high-risk ST147 clonal lineage. Following
      recognition of the outbreak, infection control measures were implemented in the
      affected areas. The outbreak continued for ca. 2 years and since then only
      sporadic cases of K. pneumoniae harbouring both carbapenemases have been
      detected.

PMID- 29654893
TI  - Molecular beta-lactamase characterization of Gram-negative pathogens recovered
      from patients enrolled in the ceftazidime-avibactam phase 3 trials (RECAPTURE 1
      and 2) for complicated urinary tract infections: Efficacies analysed against
      susceptible and resistant subsets.
AB  - This study characterized the beta-lactamase content of baseline pathogens
      recovered from patients with complicated urinary tract infections (cUTI),
      including acute pyelonephritis, who were enrolled in two phase 3 clinical trials
      of ceftazidime-avibactam (RECAPTURE 1 and 2), and correlated the clinical
      efficacy of ceftazidime-avibactam and the comparator doripenem according to
      resistance mechanisms. A total of 26.2% (93/355) ceftazidime-avibactam and 26.8%
      (101/377) doripenem patients had baseline isolates that met the MIC screening
      criteria. The majority of Enterobacteriaceae (87.5%; 154/176) carried blaCTX-M.
      This pattern was mainly observed in Escherichia coli (96.8%; 92/95) and
      Klebsiella pneumoniae (96.0%; 48/50), whereas most Proteus mirabilis (80.0%;
      8/10) carried plasmid AmpC genes. Two K. pneumoniae and 1 Klebsiella oxytoca
      carried blaOXA-48 and 1 K. pneumoniae carried blaNDM-1. Five (13/35; 37.1%)
      Pseudomonas aeruginosa isolates were screened, and 2 carbapenemase producers (IMP
      18 and VIM-2) were detected. Among patients enrolled in the ceftazidime-avibactam
      arm who were infected by MIC screen-positive Enterobacteriaceae, clinical cure
      occurred in 85.7-95.5%, regardless of beta-lactamase content; the respective rate
      in the doripenem arm was 82.1-92.5%. A total of 75.0% in the ceftazidime
      avibactam arm and 100.0% in the doripenem arm of patients infected by P.
      aeruginosa with MIC screen-positive criteria were clinically cured. Ceftazidime
      avibactam efficacy was comparable to doripenem efficacy for treating cUTI caused
      by uropathogens producing extended-spectrum and/or AmpC beta-lactamases.

PMID- 29654894
TI  - Trends in hepatitis B virus resistance to nucleoside/nucleotide analogues in
      North China from 2009-2016: A retrospective study.
AB  - Nucleos(t)ide analogues (NAs) are widely used in anti-hepatitis B virus (anti
      HBV) therapy for effective inhibition of HBV replication. However, HBV resistance
      to NAs has emerged, resulting in virus reactivation and disease recurrence. Data
      on the current dynamics of HBV resistance are still rare in China. This study
      analysed 4491 plasma samples with HBV primary genotypic resistance mutations
      representative of the general HBV resistance situation in northern China from
      2009-2016. We found that entecavir (ETV), representing 57.6% (12 713/22 060) of
      NA users in North China in 2016, has become the major NA for treating Chinese
      patients infected with HBV. Despite >50% of M204I/V+/-L180M among all HBV
      resistance cases annually and extensive exposure of patients to lamivudine (LAM),
      telbivudine (LdT) and adefovir dipivoxil (ADV), ETV resistance also showed a
      dramatically increased incidence, which rose to 17.1% in 2016. Moreover, A181T/V,
      ETV resistance mutations and multidrug resistance mutations were found more
      frequently in HBV genotype C compared with genotype B (21.2% vs. 8.5%, 12.4% vs.
      7.9% and 5.9% vs. 3.0%, respectively), whereas M204I and N236T were more
      predominant in genotype B than genotype C (40.3% vs. 20.8% and 11.3% vs. 1.8%,
      respectively). In conclusion, we report the dynamic changes of HBV NA resistance
      mutation patterns and the current NA usage profile for anti-HBV treatment in
      North China over the past 8 years. These data provide valuable information on HBV
      NA resistance that is an important reference for clinicians to devise more
      effective treatment regimens for individual patients.

PMID- 29654895
TI  - Electrostatically assembled dendrimer complex with a high-affinity protein binder
      for targeted gene delivery.
AB  - Although a variety of non-viral gene delivery systems have been developed, they
      still suffer from low efficiency and specificity. Herein, we present the assembly
      of a dendrimer complex comprising a DNA cargo and a targeting moiety as a new
      format for targeted gene delivery. A PAMAM dendrimer modified with histidine and
      arginine (HR-dendrimer) was used to enhance the endosomal escape and transfection
      efficiency. An EGFR-specific repebody, composed of leucine-rich repeat (LRR)
      modules, was employed as a targeting moiety. A polyanionic peptide was
      genetically fused to the repebody, followed by incubation with an HR-dendrimer
      and a DNA cargo to assemble the dendrimer complex through an electrostatic
      interaction. The resulting dendrimer complex was shown to deliver a DNA cargo
      with high efficiency in a receptor-specific manner. An analysis using a confocal
      microscope confirmed the internalization of the dendrimer complex and subsequent
      dissociation of a DNA cargo from the complex. The present approach can be broadly
      used in a targeted gene delivery in many areas.

PMID- 29654896
TI  - Evaluation of in vitro and in vivo antitumor effects of gambogic acid-loaded
      layer-by-layer self-assembled micelles.
AB  - This study aimed to develop a novel type of multilayer micelle using protamine
      (PRM) and hyaluronic acid (HA) for the delivery of gambogic acid (GA). GA-loaded
      micelles (GA-M) were simply andrapidly prepared using lecithin/solutol HS15 using
      a film-dispersion method. PRM and HA were added in sequence to form layer-by
      layer self-assembled micelles (HA-PRM-GA-M), in which particle size, zeta
      potential, particle morphology, drug loading, encapsulation efficiency, and in
      vitro release were investigated. Surface charge reversal demonstrated that rapid
      HA detachment exposed PRM, leading to activation of a "proton sponge" effect in
      the hyaluronidase (HAase)-rich tumor microenvironment. Compared with coumarin 6
      loaded micelles (C6-M), more efficient intracellular trafficking was observed for
      HA-PRM-C6-M, which is associated with the endosomal/lysosomal escaping ability of
      the exposed PRM. In vivo imaging showed increased enrichment of near infrared
      fluorescent dye (DIR)-loaded HA-PRM-DIR-M at the tumor site, suggesting that HA
      enhanced the active tumor targeting of GA. Furthermore, HA-PRM-GA-M showed the
      stronger antitumor activity than GA and GA-M against human lung adenocarcinoma
      (A549) tumor xenografts in nude mice. In summary, our findings show the potential
      of HA-PRM-GA-M as a novel intravenous drug carrier for the treatment of lung
      cancer.

PMID- 29654897
TI  - Qualitative and quantitative analysis of lateral diffusion of drugs in human
      skin.
AB  - This study aimed to qualitatively and quantitatively analyze lateral diffusion of
      drugs in dermatomed human skin. Lateral diffusion of calcein and methylene blue
      dyes in skin was investigated using confocal laser microscopy, calcein imaging,
      and histology studies. In in vitro permeation studies, two linear microdialysis
      probes were inserted into the dermis of untreated, poly lacto-glycolic acid
      microneedle-treated, and ablative laser-treated skin such that one was in the
      center of the diffusion area and the other was parallel, at 8 mm from the central
      probe. Skin was mounted on Franz cells, sandwiched between donor containing
      diclofenac sodium solution and receptor containing phosphate buffered saline, pH
      7.4. Qualitative techniques revealed faster lateral diffusion of the dyes in
      microneedle-treated skin than laser-treated skin. Rate of drug diffusion in the
      central probe in the microneedle-treated skin (11.8 +/- 2.5 MUg/h) was
      significantly higher than untreated and laser-treated skin (p  <  0.05). Rate of
      lateral diffusion in untreated group (0.7 +/- 0.1 MUg/h) was significantly lower
      than microneedle and laser-treated skin (p  <  0.05). Overall, in vitro
      microdialysis was demonstrated as a novel and valuable tool that can be employed
      for quantitative investigation of rate of vertical and lateral diffusion of drugs
      in intact and microporated skin.

PMID- 29654898
TI  - Improvement of intestinal transport, absorption and anti-diabetic efficacy of
      berberine by using Gelucire44/14: In vitro, in situ and in vivo studies.
AB  - This study aims to evaluate the effects of Gelucire44/14 on the in vitro
      transport, in situ intestinal absorption, as well as in vivo antidiabetic
      efficacy of berberine (BBR). In the in vitro study, Gelucire44/14 (0.1%, v/v)
      increased the absorptive transport of BBR across the intestinal membrane of a rat
      and reduced the relative transport in the secretory direction, thus demonstrating
      its potential inhibitory effect on intestinal P-glycoprotein (P-gp). In the in
      situ absorption study, Gelucire44/14 (0.1%, v/v) increased BBR absorption, and
      this enhancing effect was more significant in the ileum than in the colon of a
      rat. Oral delivery of BBR with Gelucire44/14 (0.1%, v/v) to diabetic mice,
      compared with the BBR group, induced a significant hypoglycemic effect on day 7
      and day 12 after administration. This result was well correlated with the results
      of the in vitro study, indicating the important contribution of the P-gp
      inhibitory effect of Gelucire44/14 to the improvement of the antidiabetic
      efficacy in vivo. In addition, Gelucire44/14 (0.1%, v/v) neither increased the
      levels of protein and lactate dehydrogenase in intestinal perfusion nor changed
      the morphology of the rat intestinal epithelium relative to those of the negative
      control. This finding suggested that 0.1% (v/v) Gelucire44/14 caused no apparent
      membrane damage to rat intestine. In conclusion, Gelucire44/14 exhibited
      potential for enhancing the oral absorption of BBR, thereby improving the
      antidiabetic efficacy of BBR.

PMID- 29654899
TI  - "Trans-nonachlor increases extracellular free fatty acid accumulation and de novo
      lipogenesis to produce hepatic steatosis in McArdle-RH7777 cells".
AB  - Recent studies suggest there may be an environmental exposure component to the
      development and progression of non-alcoholic fatty liver disease (NAFLD)
      involving the organochlorine (OC) pesticides or their metabolites. However, the
      roles of OC compounds in the development of NAFLD has not been fully elucidated.
      Therefore, the current study was designed to determine if exposure to trans
      nonachlor, a prevalent OC compound, could promote hepatocyte lipid accumulation
      and determine potential pro-steatotic mechanisms. McArdle-RH7777 (McA) hepatoma
      cells were incubated with trans-nonachlor for 24 h then neutral lipid
      accumulation was determined by Oil Red O staining. Exposure to trans-nonachlor
      produced a concentration dependent increase in neutral lipid accumulation. Trans
      nonachlor also increased extracellular free fatty acid-induced neutral lipid
      accumulation which appears to be due at least in part to increased free fatty
      acid accumulation as evident by increased accumulation of Bodipy labeled
      dodecanoic acid. Additionally, 14C-acetate incorporation into total cellular
      lipids was increased by trans-nonachlor implicating increased de novo lipogenesis
      (DNL) as a potential mediator of trans-nonachlor-induced neutral lipid
      accumulation. Taken together, the present data indicate exposure to trans
      nonachlor has a direct, pro-steatotic effect on hepatocytes to increase lipid
      accumulation through the combinatorial actions of extracellular free fatty acid
      accumulation and increased DNL.

PMID- 29654900
TI  - Urinary extracellular vesicle biomarkers in urological cancers: From discovery
      towards clinical implementation.
AB  - Urine contains cellular elements, biochemicals, and proteins derived from
      glomerular filtration of plasma, renal tubule excretion, and urogenital tract
      secretions that reflect an individual's metabolic and pathophysiologic state.
      Despite intensive research into the discovery of urinary biomarkers to facilitate
      early diagnosis, accurate prognosis and prediction of therapy response in
      urological cancers, none of these markers has reached widespread use. Their
      implementation into daily clinical practice is hampered by a substantial degree
      of heterogeneity in performance characteristics and uncertainty about
      reliability, clinical utility and cost-effectiveness, in addition to several
      technical limitations. Extracellular vesicles (EV) have raised interest as a
      potential source of biomarker discovery because of their role in intercellular
      communication and the resemblance of their molecular content to that of the
      releasing cells. We review currently used urinary biomarkers in the clinic and
      attempts that have been made to identify EV-derived biomarkers for urological
      cancers. In addition, we discuss technical and methodological considerations
      towards their clinical implementation.

PMID- 29654901
TI  - Ethanolamine utilization supports Clostridium perfringens growth in infected
      tissues.
AB  - Clostridium perfringens possesses the ethanolamine (EA) utilization (eut) system
      encoded within the eut operon, which utilizes the EA as a carbon, nitrogen and
      energy source. To determine the role of the eut system in C. perfringens growth,
      an in-frame deletion of the eutABC genes was made in strain HN13 to generate the
      eutABC-deleted mutant strain HY1701. Comparison of HN13 and HY1701 growth in
      media supplemented with 1.0% glucose and/or 1.0% EA showed that glucose enhanced
      the growth of both strains, whereas EA enhanced HN13 growth, but not that of
      HY1701, indicating that the eut system is necessary for C. perfringens to utilize
      EA. The two-component regulatory system EutVW is needed to induce eut gene
      expression in response to EA whereas the global virulence regulator VirRS
      differentially controlled eut gene expression depending on glucose and EA
      availability. To assess the role of the eut system in vivo, an equal number of
      HN13 and HY1701 cells were injected into the right thigh muscles of mice. Mice
      infected with HY1701 showed fewer symptoms than those injected with HN13. The
      mortality rate of mice infected with HY1701 tended to be lower than for mice
      infected with HN13. In addition, in infected tissues from mice injected with a
      mixture of HN13 and HY1701, HN13 outnumbered HY1701. PCR screening demonstrated
      that C. perfringens isolated from gas gangrene and sporadic diarrhea cases
      carried both eut genes and the perfringolysin O gene (pfoA) as well as the
      phospholipase C gene (plc). However, pfoA was not detected in isolates from food
      poisoning patients and healthy volunteers. Culture supernatants prepared from
      HN13 grown in media containing 7.5% sheep red blood cells induced significantly
      higher eutB expression levels compared to those from plc- and/or pfoA-deletion
      mutants. Together, these results indicate that the eut system plays a nutritional
      role for C. perfringens during histolytic infection.

PMID- 29654902
TI  - Characterization of extracellular virulence properties and biofilm-formation
      capacity of Vibrio species recovered from ready-to-eat (RTE) shrimps.
AB  - In this study, we evaluated the virulence factor production, biofilm-forming
      ability and cell surface properties of ready-to-eat shrimps associated vibrios
      strains. A total of 1440 ready-to-eat (RTE) shrimp samples were purchased from
      open markets in southern Nigeria, from November 2016 to October 2017. Biofilm
      formation was carried out using the microtitre plate method. Cell-to-cell
      adhesion of Vibrio species was assessed via surface hydrophobicity using the
      bacterial adherence to hydrocarbons (BATH) and salting aggregation technique,
      autoaggregation and coaggregation assay. The virulence potential of the
      identified 120 Vibrio strains includes haemolysis 107 (89.17%), lipase 106
      (88.33%), protease 108 (90%), gelatinase 111 (92.5%), the presence of surface
      layer (S-layer) 109 (90.8%) and DNA degrading activity 107 (89.17%). Biofilm
      formation at 30  degrees C tryptone soy broth in dynamic conditions revealed
      total biofilm producers for the Vibrio species as follows: V. parahaemolyticus
      (95.65%), V. vulnificus (92.86%), V. fluvialis (91.67%), V. alginolyticus
      (87.5%), V. cholerae (100%), V. mimicus (90%), V. harveyi (66.7%), and other
      Vibrio spp. (84%). A total of 50 biofilm producing vibrios using BATH technique
      include 49 (98%) hydrophilic and 1 (2%) moderately hydrophobic. Using the
      modified salting aggregation technique, 50 (100%) was characterized as
      hydrophilic. Autoaggregation index for the 12 biofilms producing Vibrio strains
      ranged from 11.6 to 41.3%, while the autoaggregation index for the 12 test
      bacteria ranged from 26.2 to 71.3%. Coaggregation between the 12 test bacteria
      with the 12 Vibrio strains ranged from 9.3 to 78.5%. However most vibrios in this
      study were hydrophilic, their hydrophilic potential is important for their
      capability to autoaggregate and coaggregate. Findings on the specific process by
      which virulent Vibrio spp. form biofilm and adhere to shrimp surface as attached
      plankton may assist in monitoring epidemics of the pathogen.

PMID- 29654903
TI  - Host cell protein removal from biopharmaceutical preparations: Towards the
      implementation of quality by design.
AB  - Downstream processing of protein products of mammalian cell culture currently
      accounts for the largest fraction of the total production cost. A major challenge
      is the removal of host cell proteins, which are cell-derived impurities. Host
      cell proteins are potentially immunogenic and can compromise product integrity
      during processing and hold-up steps. There is an increasing body of evidence that
      the type of host cell proteins present in recombinant protein preparations is a
      function of cell culture conditions and handling of the harvest cell culture
      fluid. This, in turn, can affect the performance of downstream purification steps
      as certain species are difficult to remove and may require bespoke process
      solutions. Herein, we review recent research on the interplay between upstream
      process conditions, host cell protein composition and their downstream removal in
      antibody production processes, identifying opportunities for increasing process
      understanding and control. We further highlight advances in analytical and
      computational techniques that can enable the application of quality by design.

PMID- 29654904
TI  - A de novo 921 Kb microdeletion at 11q13.1 including neurexin 2 in a boy with
      developmental delay, deficits in speech and language without autistic behaviors.
AB  - Microdeletions at 11q13.1 are very rare. At present only two patients with
      11q13.1 deletion involving neurexin 2 (NRXN2) have been reported. Both patients
      exhibited autistic features, which supported the role of NRXN2 in autism
      pathogenicity. It is currently unknown whether heterozygous deletion of NRXN2 is
      of high penetrance or if it is sufficient to result in autism behaviors. Here we
      reported a 2-year-9-month old boy with developmental delay, short stature,
      significant language delay and other congenital anomalies. In contrast to
      previously reported cases, the boy did not present with autistic behaviors and
      did not meet the clinical diagnosis of autism. A de novo 921 kb microdeletion at
      11q13.1 was detected by chromosomal microarray analysis (CMA). Whole Exome
      Sequencing (WES) was also employed for our patient. The deletion was confirmed
      and no additional pathogenic variants were detected. We compared our patient's
      genomic information and clinical features with those of two previously reported
      individuals. Three patients shared similar deleted intervals and had similar
      clinical features except for autistic behaviors. This study suggested that NRXN2
      gene had incomplete penetrance for autistic behavioral phenotype. The finding is
      of interest for genetic counseling and clinical management to patients with NRXN2
      defects.

PMID- 29654905
TI  - Family Functioning and Childhood Obesity Treatment: A Family Systems Theory
      Informed Approach.
AB  - Childhood obesity recommendations advise providers to use family-based care for
      the treatment of youth and adolescent obesity. Family-based care, defined as the
      inclusion of a caregiver and a youth, is commonly conducted through behavioral
      interventions that target the dietary and physical activity behaviors of the
      attending parent-youth dyads. However, focusing on behaviors isolated to the
      parent and youth neglects the rest of the family members, and the larger rules,
      routines, communication, and dynamics in the family. Family-based interventions
      grounded in family systems theory (FST) target family dynamics to influence
      weight-related behaviors through higher-level changes in the family. The utility
      of using FST in childhood obesity treatment has not been extensively
      conceptualized or applied. Few outcome studies have reported on variables
      representative of FST, and even fewer FST interventions have been conducted.
      Because of the lack of detail on the application of FST to childhood obesity
      treatment, providers are left with little clarity on how to use FST in clinical
      encounters. We provide the background and evidence for use of FST, detail how
      families organize around weight-related behaviors that contribute to obesity, and
      on the basis of their organization, what type of treatment might be beneficial,
      FST-informed or family-based behavioral interventions. Finally, a suggested
      family-based clinical algorithm is provided detailing the use of FST through
      assessment, intervention, and follow-up that can be refined over time by
      providers and researchers committed to viewing obesity in the context of the
      family and family dynamics.

PMID- 29654906
TI  - United States Pediatricians' Attitudes Regarding Public Policies for Low-Income
      Children and Their Profession's Advocacy Priorities.
AB  - OBJECTIVE: To examine pediatricians' attitudes toward public policies for low
      income children and the advocacy efforts for the American Academy of Pediatrics
      (AAP). METHODS: Data from the AAP Periodic Survey in October 2014 to March 2015
      were used. Respondents ranked 1) attitudes toward government programs, and 2)
      attitudes toward AAP policies on: income support, housing, education, job
      training, food, and health care. Results were analyzed according to age, gender,
      practice location, practice region, type of practice setting, and percent of
      patients with economic hardship. RESULTS: Response rate was 47% (n = 650). Most
      respondents reported that for children, the government should guarantee health
      insurance (88.9%), and food and shelter (90.0%). Most also reported that the
      government should guarantee health insurance (68.9%) and food and shelter (63.9%)
      for every citizen and to take care of people who cannot take care of themselves.
      There was variation among the level of support on the basis of practice setting.
      In multivariable analyses related to supporting the role of government for
      children and citizens, not being from the Northeast was associated with lower
      odds of support of children as well as citizens; primary care practices in rural
      areas were less supportive of government involvement related to all citizens but
      similar for children; and those younger than 40 and 50 to 59 years of age were
      more supportive of government guaranteeing enough to eat and a place to sleep for
      children. More than 55% supported the AAP advocating for income support, housing,
      education, and access to health care. CONCLUSIONS: Pediatricians strongly support
      government policies that affect child poverty and the provision of basic needs to
      families. This support should be used to inform professional organizations,
      advocates, and policy-makers focused on children and families.

PMID- 29654908
TI  - Strabismus surgery for Medicare-aged patients: more than a decade of insights.
AB  - BACKGROUND: The psychosocial and functional impact of strabismus among the
      elderly is increasingly important as life expectancy increases and factors that
      enhance the quality of life become more significant. The purpose of this study
      was to characterize the demographics, presenting complaints, health status,
      underlying etiology, and outcomes of strabismus surgery in three age cohorts of
      Medicare-aged patients. METHODS: The medical records of patients at least 65
      years of age who underwent strabismus surgery between 2004 and 2015 in a
      university-based strabismus practice were reviewed retrospectively. RESULTS: A
      total of 110 patients were identified and divided into three age cohorts for
      analysis: young-old (age 65-74), middle-old (age 75-84), and old-old (age 85+).
      At least 75% of patients in all cohorts cited diplopia as their chief complaint
      (P = 0.87). There was no difference in sex distribution, type of deviation,
      underlying etiology, or preoperative American Society of Anesthesiologists
      physical status classification scores between the cohorts (P = 0.68, P = 0.53, P
      = 0.71, P = 0.93, resp.). By the 6- to 8-week postoperative visit, 63% of all
      patients reported complete resolution of their presenting chief complaint, 23%
      reported some improvement, and 11% reported no improvement, with no difference
      between the cohorts (P = 0.12). CONCLUSIONS: Given the functional and
      psychosocial impact of strabismus in the elderly, this study lends support to
      consideration of surgery as a viable option to successfully treat strabismus
      among the oldest age cohorts.

PMID- 29654907
TI  - Vascular wall regulator of G-protein signalling-1 (RGS-1) is required for
      angiotensin II-mediated blood pressure control.
AB  - G-Protein coupled receptors (GPCRs) activate intracellular signalling pathways by
      coupling to heterotrimeric G-proteins that control many physiological processes
      including blood pressure homeostasis. The Regulator of G-Protein Signalling-1
      (RGS1) controls the magnitude and duration of downstream GPCR signalling by
      acting as a GTPase-activating protein for specific Galpha-proteins. RGS1 has
      contrasting roles in haematopoietic and non-haematopoietic cells. Rgs1-/-ApoE-/-
      mice are protected from Angiotensin II (Ang II)-induced aortic aneurysm rupture.
      Conversely, Ang II treatment increases systolic blood pressure to a greater
      extent in Rgs1-/-ApoE-/- mice than ApoE-/- mice, independent of its role in
      myeloid cells. However the precise role of RGS1 in hypertension and vascular
      derived cells remains unknown. We determined the effects of Rgs1 deletion on
      vascular function in ApoE-/- mice. Rgs1 deletion led to enhanced vasoconstriction
      in aortas and mesenteric arteries from ApoE-/- mice in response to phenylephrine
      (PE) and U46619 respectively. Rgs1 was shown to have a role in the vasculature,
      with endothelium-dependent vasodilation being impaired, and endothelium
      independent dilatation to SNP being enhanced in Rgs1-/-ApoE-/- mesenteric
      arteries. To address the downstream signalling pathways in vascular smooth muscle
      cells (VSMCs) in response to Ang II-stimulation, we assessed pErk1/2, pJNK and
      pp38 MAPK activation in VSMCs transiently transfected with Rgs1. pErk1/2
      signalling but not pJNK and pp38 signalling was impaired in the presence of Rgs1.
      Furthermore, we demonstrated that the enhanced contractile response to PE in Rgs1
      /-ApoE-/- aortas was reduced by a MAPK/Erk (MEK) inhibitor and an L-type voltage
      gated calcium channel antagonist, suggesting that Erk1/2 signalling and calcium
      influx are major effectors of Rgs1-mediated vascular contractile responses,
      respectively. These findings indicate RGS1 is a novel regulator of blood pressure
      homeostasis and highlight RGS1-controlled signalling pathways in the vasculature
      that may be new drug development targets for hypertension.

PMID- 29654909
TI  - Visual impairment evaluation in 119 children with congenital Zika syndrome.
AB  - PURPOSE: To assess visual impairment in a large sample of infants with congenital
      Zika syndrome (CZS) and to compare with a control group using the same assessment
      protocol. METHODS: The study group was composed of infants with confirmed
      diagnosis of CZS. Controls were healthy infants matched for age, sex, and
      socioeconomic status. All infants underwent comprehensive ophthalmologic
      evaluation including visual acuity, visual function assessment, and visual
      developmental milestones. RESULTS: The CZS group included 119 infants; the
      control group, 85 infants. At examination, the mean age of the CZS group was 8.5
      +/- 1.2 months (range, 6-13 months); of the controls, 8.4 +/- 1.8 months (range,
      5-12 months; P = 0.598). Binocular Teller Acuity Card (TAC) testing was abnormal
      in 107 CZS infants and in 4 controls (89.9% versus 5% [P < 0.001]). In the study
      group, abnormal monocular TAC results were more frequent in eyes with funduscopic
      alterations (P = 0.008); however, 104 of 123 structurally normal eyes (84.6%)
      also presented abnormal TAC results. Binocular contrast sensitivity was reduced
      in 87 of 107 CZS infants and in 8 of 80 controls (81.3% versus 10% [P < 0.001]).
      The visual development milestones were less achieved by infants with CZS compared
      to controls (P < 0.001). CONCLUSIONS: Infants with CZS present with severe visual
      impairment. A protocol for assessment of the ocular findings, visual acuity, and
      visual developmental milestones tested against age-matched controls is suggested.

PMID- 29654910
TI  - Surgical success and lateral incomitance following three-muscle surgery for large
      angle horizontal strabismus.

PMID- 29654911
TI  - Resolution of cystoid macular edema following arginine-restricted diet and
      vitamin B6 supplementation in a case of gyrate atrophy.
AB  - We report the outcome of 3 years of arginine-restricted diet and vitamin B6
      supplementation in a boy who presented with gyrate atrophy of the choroid and
      retina and bilateral cystoid macular edema. The diagnosis of gyrate atrophy was
      made on the basis of clinical findings and increased plasma ornithine levels.
      Molecular genetic testing revealed a disease-causing homozygous mutation in the
      ornithine aminotransferase (OAT) gene. After 3 months of dietary modification and
      pyridoxine supplementation, visual acuity improved, and optical coherence
      tomography showed resolution of cystoid macular edema in both eyes. This
      anatomical and functional improvement was maintained during 3 years of follow-up.

PMID- 29654912
TI  - Antibody Concentrations Decrease 14-Fold in Children With Celiac Disease on a
      Gluten-Free Diet but Remain High at 3 Months.
AB  - BACKGROUND & AIMS: Celiac disease can be identified by a serologic test for IgA
      against tissue transglutaminase (IgA-TTG) in a large proportion of children.
      However, the increased concentrations of antibody rarely normalize within the
      months after children are placed on a gluten-free diet (GFD). Early serologic
      predictors of sufficient adherence to GFD are required for optimal treatment.
      METHODS: In a prospective study, we observed the response to a GFD in 345
      pediatric patients (67% girls; mean age, 8.4 y) who underwent duodenal biopsy to
      confirm or refute celiac disease from October 2012 through December 2015.
      Baseline serum samples were tested centrally for IgA-TTG and IgG against
      deamidated gliadin. Follow-up serologic analyses of children on a GFD were
      performed about 3 months later. RESULTS: The geometric mean concentration of IgA
      TTG decreased from 72.4-fold to 5.2-fold the upper limit of normal (ULN), or by a
      factor of 14.0 (95% CI, 12.0-16.4). A substantial response (defined as a larger
      change than the typical variation in patients not on a GFD) was observed in 80.6%
      of the children. Only 28.1% of patients had a substantial response in the
      concentration of IgG against deamidated gliadin. Concentration of IgA-TTG
      remained above 1-fold the ULN in 83.8% of patients, and above 10-fold the ULN in
      26.6% of patients with a substantial response. CONCLUSIONS: Serum concentration
      of IgA-TTG decreases substantially in most children with celiac disease within 3
      months after they are placed on a GFD, but does not normalize in most. This
      information on changes in antibody concentrations can be used to assess patient
      response to the diet at short-term follow-up evaluations. Patients with a
      substantial response to a GFD often still have high antibody levels after 3
      months. German Clinical Trials Registry no. DRKS00003854.

PMID- 29654913
TI  - Factors Associated With Response to Placebo in Patients With Irritable Bowel
      Syndrome and Constipation.
AB  - BACKGROUND & AIMS: A high proportion of patients with irritable bowel syndrome
      (IBS) respond to placebo in clinical trials (estimated at about 40%). We aimed to
      identify factors that contribute to the high placebo response rate using data
      from a placebo-controlled trial of patients with IBS. METHODS: We performed a
      retrospective analysis of 599 women with IBS with constipation who were in the
      placebo group of a 12-week, randomized, double-blind, phase 3 trial of the
      experimental medication renzapride. Primary analyses evaluated frequency of
      abdominal pain in patients who received placebo, defined as >=30% pain
      improvement from baseline for >=6 of the 12 study weeks. We performed backward
      elimination regression with bootstrapping to identify factors associated with
      response to placebo. RESULTS: In the placebo group, 29.0% of the patients had an
      abdominal pain response. Factors associated with a response to placebo were
      baseline variation in abdominal pain (odds ratio [OR], 1.71), maximum baseline
      pain severity (OR, 1.34), and placebo response in study week 2 (OR, 2.23) or week
      3 (OR, 3.69). Factors associated with lack of response to placebo were number of
      baseline complete spontaneous bowel movements (OR, 0.73; P = .019) and final
      baseline pain ratings (OR, 0.73; P < .001). CONCLUSIONS: We identified factors
      associated with a response in abdominal pain to placebo using original data from
      an IBS clinical trial. Baseline factors associated with the placebo response in
      women with IBS and constipation included variation in baseline pain symptoms,
      severity of baseline symptoms, and early improvement of abdominal pain. These
      findings have significant implications for clinical trial design.

PMID- 29654914
TI  - Metastatic Cervical Cancer Causing Esophageal Compression and Dysphagia.

PMID- 29654915
TI  - Efficacy of MaZiRenWan, a Chinese Herbal Medicine, in Patients With Functional
      Constipation in a Randomized Controlled Trial.
AB  - BACKGROUND & AIMS: The Chinese herbal medicine, MaZiRenWan (MZRW), has been used
      for more than 2000 years to treat constipation, but it has not been tested in a
      randomized controlled trial. We performed a trial to evaluate the efficacy and
      safety of MZRW, compared with the stimulant laxative senna or placebo, for
      patients with functional constipation (FC). METHODS: We performed a double-blind,
      double-dummy, trial of 291 patients with FC based on Rome III criteria, seen at 8
      clinics in Hong Kong from June 2013 through August 2015. Patients were observed
      for 2 weeks and then assigned randomly (1:1:1) to groups given MZRW (7.5 g, twice
      daily), senna (15 mg daily), or placebo for 8 weeks. Patients were then followed
      for 8 weeks and evaluated at baseline and weeks 4, 8 (end of treatment), and 16
      (end of follow up). Participants recorded information on stool form and
      frequency, feeling of complete evacuation, and research medication taken. Data on
      individual bowel symptoms, global symptom improvement, and adverse events were
      collected. A complete response was defined as an increase >=1 complete
      spontaneous bowel movement (CSBM)/week from baseline (the primary outcome).
      Secondary outcomes included response during the follow-up period, colonic
      transit, individual and global symptom assessments, quality of life measured with
      36-item short form Chinese version, and adverse events. RESULTS: Although there
      was no statistically significant difference in proportions of patients with a
      complete response to MZRW (68%) vs. senna (57.7%) (P = .14) at week 8, there was
      a statistically significant difference vs. placebo (33.0%) (P < .005). At the 16
      week timepoint (after the 8-week follow-up period), 47.4% of patients had a
      complete response to MZRW, 20.6% had a complete response to senna, and 17.5% had
      a complete response to placebo (P < .005 for MZRW vs. placebo). The group that
      received MZRW group also had significant increases in colonic transit and reduced
      severity of constipation, straining, incomplete evacuation, and global
      constipation symptoms compared with the groups that received placebo or senna in
      (P < .05 for all comparisons). CONCLUSIONS: In a randomized controlled trial of
      291 patients with FC, we found MZRW to be well-tolerated and effective in
      increasing CSBM/week. MZRW did not appear to be more effective than senna and
      might be considered as an alternative to this drug. ClincialTrials.gov no:
      NCT01695850.

PMID- 29654916
TI  - Endoscopic Management of Octopus Food Bolus Lodged Within the Esophagus.

PMID- 29654917
TI  - Lifestyle Factors in Late Adolescence Associate With Later Development of
      Diverticular Disease Requiring Hospitalization.
AB  - BACKGROUND & AIMS: The burden of diverticular disease on society is high and is
      increasing with an aging population. It is therefore important to identify risk
      factors for disease development or progression. Many lifestyle behaviors during
      adolescence affect risk for later disease. We searched for adolescent lifestyle
      factors that affect risk of diverticular disease later in life. METHODS: We
      performed a retrospective analysis of data from 43,772 men (age, 18-20 y)
      conscripted to military service in Sweden from 1969 through 1970, with a follow
      up period of 39 years. All conscripts underwent an extensive mental and physical
      health examination and completed questionnaires covering alcohol consumption,
      smoking, and use of recreational drugs; cardiovascular fitness was assessed using
      an ergometer cycle at the time of conscription. Outcome data were collected from
      national registers to identify discharge diagnoses of diverticular disease until
      the end of 2009. We performed Cox regression analysis to determine whether body
      mass index, cardiovascular fitness, smoking, use of recreational drugs, alcohol
      consumption, and risky use of alcohol, at time of conscription are independent
      risk factors for development of diverticular disease. RESULTS: Overweight and
      obese men had a 2-fold increased risk of diverticular disease compared to normal
      weight men (hazard ratio, 2.00; P < .001). A high level of cardiovascular fitness
      was associated with a reduced risk of diverticular disease requiring
      hospitalization (P = .009). Smoking (P = .003), but not use of recreational drugs
      (P = .11), was associated with an increased risk of diverticular disease
      requiring hospitalization. Risky use of alcohol, but not alcohol consumption per
      se, was associated with a 43% increase in risk of diverticular disease requiring
      hospitalization (P = .007). CONCLUSIONS: In a retrospective analysis of data from
      43,772 men in Sweden, we associated being overweight or obese, a smoker, a high
      risk user of alcohol, and/or having a low level of cardiovascular fitness in late
      adolescence with an increased risk of developing diverticular disease requiring
      hospitalization later in life. Improving lifestyle factors among adolescents
      might reduce the economic burden of diverticular disease decades later.

PMID- 29654919
TI  - Jejunal Ectopic Pancreas.

PMID- 29654918
TI  - Reduced Unplanned Care and Disease Activity and Increased Quality of Life After
      Patient Enrollment in an Inflammatory Bowel Disease Medical Home.
AB  - BACKGROUND & AIMS: Specialty medical homes (SMHs) are a new health care model in
      which a multidisciplinary team and specialists manage patients with chronic
      diseases. As part of a large integrated payer-provider network, we formed an
      inflammatory bowel diseases (IBDs) SMH and investigated its effects on health
      care use, disease activity, and quality of life (QoL). METHODS: We performed a
      retrospective analysis of 322 patients (58% female; mean age, 34.6 y; 62% with
      Crohn's disease; 32% with prior IBD surgery) enrolled in an IBD SMH, in
      conjunction with the University of Pittsburgh Medical Center Health Plan, from
      June 2015 through July 2016. Patients had at least 1 year of follow up. We
      evaluated changes in numbers of emergency department visits and hospitalizations
      from the year before vs after SMH enrollment. Secondary measures included IBD
      activity assessments and QoL. RESULTS: Compared to the year before IBD SMH
      enrollment, patients had a 47.3% reduction in emergency department visits (P <
      .0001) and a 35.9% reduction in hospitalizations (P = .008). In the year
      following IBD SMH enrollment, patients had significant reductions in the median
      Harvey-Bradshaw Index score (reduced from 4 to 3.5; P = .002), and median
      ulcerative colitis activity index score (from 4 to 3; P = .0003), and increases
      in QoL (median short inflammatory bowel disease questionnaire score increased
      from 50 to 51.8; P < .0001). Patients in the most extreme (highest and lowest)
      quartiles had the most improvement when we compared scores at baseline vs after
      enrollment. Based on multivariable regression analysis, use of corticosteroids
      (odds ratio [OR], 2.72; 95% CI, 1.32-5.66; P = .007) or opioids (OR, 3.20; 95%
      CI, 1.32-7.78; P = .01), and low QoL (OR, 4.44; 95% CI, 1.08-18.250; P = .04) at
      enrollment were significantly associated with persistent emergency department
      visits and hospitalizations. CONCLUSIONS: We found development of an IBD SMH to
      be feasible and significantly reduce unplanned care and disease activity and
      increase patient QoL 1 year after enrollment.

PMID- 29654920
TI  - Myristic acid induces proteomic and secretomic changes associated with steatosis,
      cytoskeleton remodeling, endoplasmic reticulum stress, protein turnover and
      exosome release in HepG2 cells.
AB  - : Myristic acid, the 14-carbon saturated fatty acid (C14:0), is associated to an
      increased cardiovascular disease risk. Since it is found in low concentration in
      cells, its specific properties have not been fully analyzed. The aim of this
      study was to explore the cell response to this fatty acid to help explaining
      clinical findings on the relationship between C14:0 and cardiovascular disease.
      The human liver HepG2 cell line was used to investigate the hepatic response to
      C14:0 in a combined proteomic and secretomic approach. A total of 47
      intracellular and 32 secreted proteins were deregulated after treatments with
      different concentrations of C14:0. Data are available via ProteomeXchange
      (PXD007902). In addition, C14:0 treatment of primary murine hepatocytes confirmed
      that C14:0 induces lipid droplet accumulation and elevates perilipin-2 levels.
      Functional enrichment analysis revealed that C14:0 modulates lipid droplet
      formation and cytoskeleton organization, induce ER stress, changes in exosome and
      extracellular miRNA sorting in HepG2cells. Our data provide for the first time a
      proteomic profiling of the effects of C14:0 in human hepatoma cells and
      contribute to the elucidation of molecular mechanisms through which this fatty
      acid may cause adverse health effects. BIOLOGICAL SIGNIFICANCE: Myristic acid is
      correlated with an increase in plasma cholesterol and mortality due to
      cardiovascular diseases. This study is the first example of an integration of
      proteomic and secretomic analysis of HepG2 cells to investigate the specific
      properties and functional roles of myristic acid on hepatic cells. Our analyses
      will lead to a better understanding of the myristic acid induced effects and can
      elicit new diagnostic and treatment strategies based on altered proteins.

PMID- 29654921
TI  - Putative salivary biomarkers useful to differentiate patients with fibromyalgia.
AB  - Fibromyalgia (FM) is a chronic pain disorder characterized by widespread pain and
      associated with unspecific symptoms. So far, no laboratory tests have been
      validated. The aim of the present study was to investigate the presence in saliva
      of potential diagnostic and/or prognostic biomarkers which could be useful for
      the management of FM patients. Specifically, the salivary profile of FM patients
      was compared with those of healthy subjects, subjects suffering migraine (model
      of non-inflammatory chronic pain), and patients affected by rheumatoid arthritis
      (model of inflammatory chronic pain). For proteomics analysis 2-DE and SELDI-TOF
      MS were applied. From 2-DE serotransferrin and alpha-enolase were found
      differentially expressed in FM. Hence, their expression was validated by ELISA
      together with phosphoglycerate-mutase-I and transaldolase, which were found in a
      previous work. Moreover, ROC curve was calculated by comparing FM patients versus
      control subjects (healthy plus migraine) to investigate the discriminative power
      of biomarkers. The best performance was obtained by combining alpha-enolase,
      phosphoglycerate-mutase-I and serotransferrin. On the other hand, none of the
      candidate proteins showed a statistical correlation with clinical features.
      Finally, preliminary SELDI analysis highlighted two peaks whose identification
      need to be validated. Overall, these results could be useful in supporting the
      clinical diagnosis of FM. SIGNIFICANCE: FM is one of the most common chronic pain
      condition which is associated with significant disability. The fibromyalgic pain
      is a peculiar characteristic of this disease and FM patients suffer from reduced
      quality of life, daily functioning and productivity. Considering the deep
      complexity of FM, the discovery of more objective markers is crucial for
      supporting clinical diagnosis. Therefore, the aim of the present study was the
      selection of biomarkers effectively associated with fibromyalgic pain which will
      enable clinicians to achieve an unambiguous diagnosis, and to improve approaches
      to patients' management. We defined a panel of 3 salivary proteins which could be
      one of the criteria to be taken into account. Consequently, the identification of
      disease salivary biomarkers could be helpful in detecting FM clusters and
      targeted treatment. Actually, our future perspective foresees to develop a
      simple, rapid and not invasive point-of-care testing which will be of use during
      the diagnostic process. In addition, the present results can offer a clue for
      shedding light upon the complex entity of such a disease like FM.

PMID- 29654923
TI  - Analysis of codon usage pattern of infectious laryngotracheitis virus immunogenic
      glycoproteins and its biological implications.
AB  - Infectious laryngotracheitis virus (ILTV) is a highly contagious acute
      respiratory poultry pathogen. Modified live ILTV vaccines are the only control
      against ILT infections. Reversions and establishment of latent infections are the
      major concerns imparting the need to develop safer vaccines against ILTV
      infection. ILTV glycoprotein B and D (gB and gD) are major protective immunogens.
      The factors shaping synonymous codon usage bias and nucleotide composition in
      ILTV glycoprotein genes have not yet been reported. In the present study, we have
      analyzed the synonymous codon usage indices of ILTV gB and gD genes. Variation in
      the codon usage was seen in both the glycoproteins majorly by mutational
      pressure. The pattern was determined using the correspondence analysis, effective
      number of codon (Nc), GC3 plot and correlation analyses among different indices.
      The study is a comprehensive analysis of the codon usage patterns of ILTV
      glycoprotein genes. This will be helpful in understanding the codon usage bias of
      ILTV and related DNA viruses which could further explore its biology.

PMID- 29654922
TI  - Comparative qualitative phosphoproteomics analysis identifies shared
      phosphorylation motifs and associated biological processes in evolutionary
      divergent plants.
AB  - : Phosphorylation is one of the most prevalent post-translational modifications
      and plays a key role in regulating cellular processes. We carried out a
      bioinformatics analysis of pre-existing phosphoproteomics data, to profile two
      model species representing the largest subclasses in flowering plants the dicot
      Arabidopsis thaliana and the monocot Oryza sativa, to understand the extent to
      which phosphorylation signaling and function is conserved across evolutionary
      divergent plants. We identified 6537 phosphopeptides from 3189 phosphoproteins in
      Arabidopsis and 2307 phosphopeptides from 1613 phosphoproteins in rice. We
      identified phosphorylation motifs, finding nineteen pS motifs and two pT motifs
      shared in rice and Arabidopsis. The majority of shared motif-containing proteins
      were mapped to the same biological processes with similar patterns of fold
      enrichment, indicating high functional conservation. We also identified shared
      patterns of crosstalk between phosphoserines with enrichment for motifs pSXpS,
      pSXXpS and pSXXXpS, where X is any amino acid. Lastly, our results identified
      several pairs of motifs that are significantly enriched to co-occur in
      Arabidopsis proteins, indicating cross-talk between different sites, but this was
      not observed in rice. SIGNIFICANCE: Our results demonstrate that there are
      evolutionary conserved mechanisms of phosphorylation-mediated signaling in
      plants, via analysis of high-throughput phosphorylation proteomics data from key
      monocot and dicot species: rice and Arabidposis thaliana. The results also
      suggest that there is increased crosstalk between phosphorylation sites in A.
      thaliana compared with rice. The results are important for our general
      understanding of cell signaling in plants, and the ability to use A. thaliana as
      a general model for plant biology.

PMID- 29654924
TI  - Reservoir and vector evolutionary pressures shaped the adaptation of Borrelia.
AB  - The life cycle of spirochetes of the genus Borrelia includes complex networks of
      vertebrates and ticks. The tripartite association of Borrelia-vertebrate-tick has
      proved ecologically successful for these bacteria, which have become some of the
      most prominent tick-borne pathogens in the northern hemisphere. To keep
      evolutionary pace with its double-host life history, Borrelia must adapt to the
      evolutionary pressures exerted by both sets of hosts. In this review, we attempt
      to reconcile functional, phylogenetic, and ecological perspectives to propose a
      coherent scenario of Borrelia evolution. Available empirical information supports
      that the association of Borrelia with ticks is very old. The major split between
      the tick families Argasidae-Ixodidae (dated some 230-290 Mya) resulted in most
      relapsing fever (Rf) species being restricted to Argasidae and few associated
      with Ixodidae. A further key event produced the diversification of the Lyme
      borreliosis (Lb) species: the radiation of ticks of the genus Ixodes from the
      primitive stock of Ixodidae (around 217 Mya). The ecological interactions of
      Borrelia demonstrate that Argasidae-transmitted Rf species remain restricted to
      small niches of one tick species and few vertebrates. The evolutionary pressures
      on this group are consequently low, and speciation processes seem to be driven by
      geographical isolation. In contrast to Rf, Lb species circulate in nested
      networks of dozens of tick species and hundreds of vertebrate species. This
      greater variety confers a remarkably variable pool of evolutionary pressures,
      resulting in large speciation of the Lb group, where different species adapt to
      circulate through different groups of vertebrates. Available data, based on ospA
      and multilocus sequence typing (including eight concatenated in-house genes)
      phylogenetic trees, suggest that ticks could constitute a secondary bottleneck
      that contributes to Lb specialization. Both sets of adaptive pressures contribute
      to the resilience of highly adaptable meta-populations of bacteria.

PMID- 29654926
TI  - Fine-Tuning of Eui1: Breaking the Bottleneck in Hybrid Rice Seed Production.

PMID- 29654925
TI  - Effects of bisphenol A (BPA) on brain-specific expression of cyp19a1b gene in
      swim-up fry of Labeo rohita.
AB  - Estrogen regulates numerous developmental and physiological processes and effects
      are mediated mainly by estrogenic receptors (ERs), which function as ligand
      regulated transcription factor. ERs can be activated by many different types
      endocrine disrupting chemicals (EDCs) and interfere with behaviour and
      reproductive potential of living organism. Estrogenic regulation of membrane
      associated G protein-coupled estrogen receptor, GPER activity has also been
      reported. Bisphenol A (BPA), a ubiquitous endocrine disruptor is present in many
      household products, has been linked to many adverse effect on sexual development
      and reproductive potential of wild life species. The present work is aimed to
      elucidate how an environmentally pervasive chemical BPA affects in vivo
      expression of a known estrogen target gene, cyp19a1b in the brain, and a known
      estrogenic biomarker, vitellogenin (Vg) in the whole body homogenate of 30 days
      post fertilization (dpf) swim-up fry of Labeo rohita. We confirm that, like
      estrogen, the xenoestrogen BPA exposure for 5-15 days induces strong
      overexpression of cyp19a1b, but not cyp19a1a mRNA in the brain and increase
      concentration of vitellogenin in swim-up fry. BPA also induces strong
      overexpression of aromatase B protein and aromatase activity in brain.
      Experiments using selective modulators of classical ERs and GPER argue that this
      induction is largely through nuclear ERs, not through GPER. Thus, BPA has the
      potential to elevate the levels of aromatase and thereby, levels of endogenous
      estrogen in developing brain. These results indicate that L. rohita swim-up fry
      can be used to detect environmental endocrine disruptors either using cyp19a1b
      gene expression or vitellogenin induction.

PMID- 29654927
TI  - Prognostic Impact of Tumor Mutation Burden in Patients With Completely Resected
      Non-Small Cell Lung Cancer: Brief Report.
AB  - INTRODUCTION: Tumor mutation burden (TMB) is thought to be associated with the
      amount of neoantigen in the tumor and to have an important role in predicting the
      effect of immune checkpoint inhibitors. However, the relevance of TMB to
      prognosis is not yet fully understood. In this study, we investigated the
      clinical significance of TMB in patients with NSCLC and examined the relationship
      between TMB and prognosis. METHODS: We calculated TMB within individual tumors by
      whole-exome sequencing analysis using next-generation sequencing. We included
      that there were 90 patients with NSCLC who underwent surgery in the Hospital of
      Fukushima Medical University from 2013 to 2016. No patients received chemotherapy
      or immunotherapy before surgery. We assessed the correlation between TMB and
      prognosis. RESULTS: TMB greater than 62 was associated with worse overall
      survival (OS) of patients with NSCLC (hazard ratio [HR] = 6.633, p = 0.0003).
      Multivariate analysis showed poor prognosis with high TMB (HR = 12.31, p =
      0.019). In patients with stage I NSCLC, higher TMB was associated with worse
      prognosis for both OS (HR = 7.582, p = 0.0018) and disease-free survival (HR =
      6.07, p = 0.0072). CONCLUSIONS: High TMB in NSCLC is a poor prognostic factor. If
      high TMB is a predictor of the efficacy of immune checkpoint inhibitors,
      postoperative adjuvant therapy with immune checkpoint inhibitors may contribute
      to improvement of recurrence and OS.

PMID- 29654928
TI  - Progress in the Management of Early-Stage Non-Small Cell Lung Cancer in 2017.
AB  - The landscape of care for early-stage non-small cell lung cancer continues to
      evolve. While some of the developments do not seem as dramatic as what has
      occurred in advanced disease in recent years, there is a continuous improvement
      in our ability to diagnose disease earlier and more accurately. We have an
      increased understanding of the diversity of early-stage disease and how to better
      tailor treatments to make them more tolerable without impacting efficacy. The
      International Association for the Study of Lung Cancer and the Journal of
      Thoracic Oncology publish this annual update to help readers keep pace with these
      important developments. Experts in the care of early-stage lung cancer patients
      have provided focused updates across multiple areas including screening,
      pathology, staging, surgical techniques and novel technologies, adjuvant therapy,
      radiotherapy, surveillance, disparities, and quality of life. The source for
      information includes large academic meetings, the published literature, or novel
      unpublished data from other international oncology assemblies.

PMID- 29654929
TI  - A randomized controlled trial of community health workers using patient stories
      to support hypertension management: Study protocol.
AB  - BACKGROUND: Uncontrolled hypertension is a significant public health problem in
      the U.S. with about one half of people able to keep blood pressure (BP) under
      control. Uncontrolled hypertension leads to increased risk of stroke, heart
      attack, and death. Furthermore, the social and economic costs of poor
      hypertension control are staggering. People living with hypertension can benefit
      from additional educational outreach and support. METHODS: This randomized trial
      conducted at two Community Health Centers (CHCs) in Massachusetts assessed the
      effect of community health workers (CHWs) assisting patients with hypertension.
      In addition to the support provided by CHWs, the study uses video narratives from
      patients who have worked to control their BP through diet, exercise, and better
      medication adherence. Participants enrolled in the study were randomly assigned
      to immediate intervention (I) by CHWs or a delayed intervention (DI) (4 to 6
      months later). Each participant was asked to meet with the CHW 5 times (twice in
      person and three times telephonically). Study outcomes include systolic and
      diastolic BP, diet, exercise, and body mass index. CONCLUSION: CHWs working
      directly with patients, using multiple approaches to support patient self
      management, can be effective agents to support change in chronic illness
      management. Moreover, having culturally appropriate tools, such as narratives
      available through videos, can be an important, cost effective aid to CHWs.
      Recruitment and intervention delivery within a busy CHC environment required
      adaptation of the study design and protocols for staff supervision, data
      collection and intervention delivery and lessons learned are presented.
      RETROSPECTIVE TRIAL REGISTRATION: Clinical Trials.gov registration submitted
      8/17/16: Protocol ID# 5P60MD006912-02 and Clinical trials.gov ID# NCT02874547
      Community Health Workers Using Patient Stories to Support Hypertension
      Management.

PMID- 29654930
TI  - Does food addiction contribute to excess weight among clinic patients seeking
      weight reduction? Examination of the Modified Yale Food Addiction Survey.
AB  - BACKGROUND: Despite controversy surrounding the construct of food addiction, its
      relationship with obesity and the validity of the Yale Food Addiction Scale
      (YFAS), have become emerging fields of study. No prior research has examined the
      prevalence and correlates of food addiction, and validation of the Modified Yale
      Food Addiction Scale (mYFAS), in a non-research based weight management clinic
      setting. OBJECTIVE: The current study sought to examine the validity of a brief
      version of the Yale Food Addiction Scale in weight loss seeking patients, and to
      determine whether food addiction contributes to excess weight in this patient
      population. PARTICIPANTS: The sample consisted of 126 Veterans with
      overweight/obesity who attended an orientation session for a weight management
      program. Participants (mean age = 61.8 years, mean BMI = 38.0, male = 89.7%,
      Caucasian = 76.0%) completed questionnaires related to food addiction, weight and
      eating, and mental health and behavior. RESULTS: Ten percent of the sample met
      diagnostic threshold for food addiction. Correlational analysis revealed that
      food addiction was significantly and highly correlated with BMI, emotional
      eating, night eating and screens for depression and insomnia (p's < 0.001);
      significantly correlated with eating pathology, and screening for PTSD (p's <
      0.05); and inversely correlated with screening for alcohol use disorders (p <
      0.01). The prevalence of food addiction was significantly higher in participants
      with Binge Eating Disorder (75%) compared to participants without (5.4%; p <
      0.001). Food addiction uniquely accounted for 15% of the variance of BMI, almost
      three times more than general eating disorder pathology. DISCUSSION: This study
      provides further evidence for the validity of the mYFAS, and clinical
      significance of the food addiction construct among weight loss seeking patients
      in non-research based weight management settings. Findings confirm that food
      addiction contributes to excess weight among clinic patients seeking weight
      reduction above and beyond the effects of disordered eating. It is recommended
      that clinicians and researchers consider an addiction framework for addressing
      comorbid overweight and food addiction among afflicted individuals seeking weight
      loss.

PMID- 29654931
TI  - Alpha lipoic acid attenuates cadmium-induced nephrotoxicity via the mitochondrial
      apoptotic pathways in rat.
AB  - Alpha lipoic acid (alpha-LA), a potent antioxidant, is protective against acute
      nephrotoxicity. In the present study, the attenuation of cadmium (Cd)-induced
      kidney injury by alpha-LA on was investigated in a rat model. Exposure to 50 mg/L
      Cd for 12 weeks increased kidney index and Cd content, malondialdehyde (MDA)
      levels, and histological damage to the renal cortex, and decreased the activities
      of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT),
      and glutathione (GSH). Treatment with 50 mg/L Cd also damaged renal cell
      mitochondria and nuclei, and activated the mitochondrial apoptosis pathway,
      indicated by increased gene and protein expression/activation of caspase-9,
      caspase-3, poly ADP-ribose polymerase (PARP) and Bcl-2 adenovirus E1a nineteen
      kilodalton interacting protein 3 (BNIP3), and translocation of cytochrome c (cyt
      c), apoptosis-inducing factor (AIF), and endonuclease G (Endo G). However,
      simultaneous supplementation with alpha-LA (50 mg/kg.bw) protected kidney cells
      from Cd-induced cytotoxicity by reducing MDA levels and Cd content, restoring
      endogenous enzyme activities, renewing mitochondrial function, and preventing
      activation of the mitochondria apoptosis pathway.

PMID- 29654932
TI  - Using the "Hill-Sachs interval to glenoid track width ratio" for prediction of
      recurrent instability after arthroscopic Bankart repair.
AB  - INTRODUCTION: The glenoid track concept was used to confirm the engaging Hill
      Sachs lesion (HSL) as a risk factor for recurrent instability following
      arthroscopic Bankart repair (ABR). However, the post-operative condition of soft
      tissue in vivo was not comparable to that designed in the intact condition in
      vitro in the original study of the glenoid track concept. Herein, the possibility
      of engagement may be underestimated. HYPOTHESIS: A threshold of the Hill-Sachs
      interval to glenoid track width ratio (H/G ratio) that is related to recurrent
      instability after ABR could be found, in order to adjust the original glenoid
      track concept. PATIENTS AND METHODS: Patients who underwent ABR with minimum 24
      months follow-up were reviewed retrospectively. The primary outcome was evaluated
      with the recurrent instability. The H/G ratio of individual patients was used to
      calculate the sensitivity, specificity, and a receiver operating characteristic
      (ROC) curve, which aimed to establish a H/G ratio threshold related to recurrent
      instability after ABR. RESULTS: From June 2005 to December 2013, 160 patients
      with a mean age of 27.7years were enrolled. The mean follow-up period was 77.2
      months. The ROC curve indicated that H/G ratio>=0.7 had the sensitivity and
      specificity of 0.74 and 0.71, respectively, in predicting recurrent instability.
      On univariate logistic regression analysis, the H/G ratio>=0.7 was a significant
      predictor of higher risk for recurrent instability (p<0.001). DISCUSSION: H/G
      ratio seems to be a reliable parameter for predicting recurrent instability. H/G
      ratio>=0.7 may be considered as a positive predictor for recurrent instability
      after ABR. LEVEL OF EVIDENCE: Level IV: retrospective diagnostic study.

PMID- 29654933
TI  - No-go decision: A newly identified adverse event in orthopaedic surgery - causes
      and medico-legal implications.
AB  - BACKGROUND: No-go designates a decision not to perform surgery when it becomes
      apparent that safety and/or feasibility requirements are not met. No-go decisions
      can occur at any time between patient admission to a hospital department and
      immediately before the first incision. The primary objective of this study was to
      assess the causes of no-go decisions reported as healthcare-associated adverse
      events (HAAEs). HYPOTHESIS: Most no-go decisions in orthopaedic surgery are
      related to problems with medical devices. MATERIAL AND METHODS: A preliminary
      retrospective study assessed HAAEs reported over the 1-year period from 1st
      October 2014 to 30th September 2015, using the risk-management tool ALARM. A
      prospective survey was then performed by emailing a 15-item questionnaire to the
      1828 members of Orthorisq (the French orthopaedic surgeon accreditation agency).
      Responses were either yes/no or open. Statistical comparisons were performed,
      using the paired Wilcoxon signed-rank test to estimate p values. RESULTS: Among
      reported HAAEs, 5.6% were no-go decisions. Of the 101 reported no-go decisions,
      43.5% and 45.2% were due to problems with managing implantable medical devices in
      the retrospective and prospective assessments, respectively. In over 85% of
      cases, surgery was cancelled or postponed. Over half the no-go decisions were
      associated with unnecessary anaesthesia. Checklist completion was performed in
      only half the cases and was not associated with no-go decisions (p>0.8).
      DISCUSSION: This study provides descriptive data on no-go decisions in
      orthopaedic surgery. Healthcare professionals use many methods to enhance patient
      safety by preventing adverse events or diminishing their impact. Errors in
      managing implantable medical devices are the leading cause of no-go decisions.
      The current checklist is not appropriate for managing implantable medical devices
      in orthopaedic surgery, in part because it does not include checking devices upon
      receipt. Before surgery, patients should be informed of the risk of a no-go
      decision, since unnecessary anaesthesia occurs in over half the cases. LEVEL OF
      EVIDENCE: IV, prospective study.

PMID- 29654934
TI  - Humeral metastasis of renal cancer: Surgical options and review of literature.
AB  - INTRODUCTION: The humerus is the second most common long bone site of metastatic
      disease from renal cell carcinomas (RCC) after femur. Surgery has an important
      role in the treatment of these lesions due to renal cell tumor's resistance to
      chemotherapy and radiotherapy. HYPOTHESIS: Prosthetic replacement is an effective
      and safe solution in treatment of renal humeral metastasis. MATERIAL AND METHODS:
      Fifty-six patients affected by RCC bone metastases of the humerus that underwent
      a surgical reconstruction were rewised. Thirty-five lesions were localized on
      proximal third, 12 on the shaft, 9 on distal third. Among proximal 29 were
      treated with resection and endoprosthetic replacement and 6 with plate and
      cement. Six diaphyseal lesions were stabilized with intramedullary nailing, 5
      with plate and cement and 1 with an intercalary prosthesis. Regarding distal
      lesions, 7 elbow prostheses and 2 plates and cement were used. RESULTS: The
      average age was 63years. Metastasis was single in 55% of cases, and in 45%
      metachronous. A pathologic fracture (PF) occurred in 64% of cases. Only 9% of
      patients had a mechanical complication, 7% an infection and 5% neurological
      deficit. A local recurrence occurred in 14% of patients. An implant failure has
      been observed in 10 patients, 5 for mechanical complications, 2 for infections
      and 3 for local recurrence; of these 7 were treated with a prosthesis and 3 with
      plate and cement. The mean value of MSTS score was 64%, 63% and 59% respectively
      in patients with proximal, diaphyseal and distal humerus metastases. DISCUSSION:
      Solitary and metachronous bone metastases have a longer survival. Disease-free
      interval>2years is another important prognostic factor. Reconstruction with a
      modular prosthesis is recommended in proximal and distal third. Instead in
      diaphyseal lesions a closed reduction and fixation with intramedullary locked
      nailing are preferred. When surgical indications are correctly followed, good
      oncologic and functional outcomes are obtained, leading to markedly improvement
      of patients' quality of life. RETROSPECTIVE STUDY: Level of evidence: IV.

PMID- 29654935
TI  - Functional assessment of transplantar nailing for ankle fracture in the elderly:
      48 weeks' prospective follow-up of 14 patients.
AB  - INTRODUCTION: Retrograde transplantar intramedullary nailing (TIMN) is a recently
      described option for ankle fracture in elderly patients with multiple comorbidity
      contraindicating classical internal fixation. The main objective of the present
      study was to assess mobility after TIMN for ankle fracture in the elderly. The
      secondary objective was to assess complications. HYPOTHESIS: Retrograde TIMN
      provides reliable fixation of ankle fracture in the elderly, enabling early
      resumption of walking. MATERIAL AND METHODS: Fourteen patients, with a mean age
      of 79.6years (range: 65-99years), with fracture of the ankle or tibial pilon
      treated by retrograde TIMN, were prospectively included over a 1-year period
      (2014-2016). Full weight-bearing with walking cast boot was authorized as of day
      1. Mobility was assessed on Parker score in consultation at 6, 12, 24 and 48
      weeks. RESULTS: Ten patients were followed up. Mean Parker score was 3.6 (range:
      1-5) preoperatively, and 2.4 (range: 1-5) and 2.7 (range: 1-5) at 24 and 48
      weeks, respectively: i.e., not significantly different from preoperative values
      (p=0.057 and p=0.054, respectively). There were no decubitus-related
      complications. Two patients (20%) showed other complications, including 1 deep
      infection requiring material ablation. Consolidation was systematic, without
      hindfoot malunion. DISCUSSION: Retrograde TIMN appeared to be a useful option for
      ankle fracture in elderly patients for whom classical internal fixation was
      contraindicated. It allowed immediate resumption of weight-bearing and early
      rehabilitation, with no increased morbidity or mortality. LEVEL OF EVIDENCE: IV.

PMID- 29654936
TI  - The CJOrtho app: A mobile clinical and educational tool for orthopedics.
AB  - The need for modern patient evaluation tools continues to grow. A dependable and
      reproducible assessment provides objective follow-up and increases the validity
      of collected data. This is where mobile apps come into play, as they provide a
      link between surgeons and patients. They also open the possibility of interacting
      with other healthcare staff to exchange common scientific reference systems and
      databases. The CJOrtho app provides fast access to 65 classification systems in
      orthopedics or trauma surgery, 20 clinical outcome scores and a digital
      goniometer. The development of free mobile apps is an opportunity for education
      and better follow-up, while meeting the demands of patients.

PMID- 29654937
TI  - Cognition, health-related quality of life, and mood in children and young adults
      diagnosed with a glioneuronal tumor in childhood.
AB  - AIMS: The aim of this study was to investigate long-term cognitive outcome,
      health-related quality of life (HRQoL), and psychiatric symptoms in children and
      young adults diagnosed with a glioneuronal tumor in childhood. METHODS: Twenty
      eight children and adolescents (0-17.99years) with a minimum postoperative follow
      up time of five years were eligible for the study; four persons declined
      participation. A cross-sectional long-term follow-up evaluation was performed
      using the following study measures: Wechsler Intelligence Scale for Children
      (WISC-IV) or Wechsler Adult Intelligence Scale (WAIS-IV), Reys Complex Figure
      Test (RCFT), Short Form 36 version 2 (SF-36v2), Short Form 10 (SF-10), Quality of
      Life in Epilepsy 31 (QOLIE-31), Hospital Anxiety Depression Scale (HADS) or Beck
      Youth Inventory Scales (BYI), and Rosenberg Self-Esteem Scale. Historical WISC
      III and RCFT data were used to compare cognitive longitudinal data. RESULTS: Mean
      follow-up time after surgery was 12.1years. Sixty-three percent (15/24) were
      seizure-free. Despite a successive postoperative gain in cognitive function, a
      significant reduction relative to norms was seen in the seizure-free group with
      respect to perceptual reasoning index (PRI), working memory index (WMI), and full
      scale intelligence quotient (FSIQ). Seizure freedom resulted in acceptable HRQoL.
      Thirty-two percent and 16% exceeded the threshold level of possible anxiety and
      depression, respectively, despite seizure freedom. CONCLUSION: Although lower
      than in corresponding reference groups, cognitive outcome and HRQoL are good
      provided that seizure freedom or at least a low seizure severity can be achieved.
      There is a risk of elevated levels of psychiatric symptoms. Long-term clinical
      follow-up is advisable.

PMID- 29654939
TI  - Is training sufficient for ultrasound operators to diagnose deep infiltrating
      endometriosis and bowel involvement by transvaginal ultrasound?
AB  - OBJECTIVES: To assess and compare the diagnostic accuracy of transvaginal
      ultrasonography (TVUS) by trained or untrained ultrasound operators in deep
      infiltrating endometriosis (DIE) imaging, for diagnosing DIE and bowel
      involvement. METHODS: This was an observational study of patients with clinically
      suspected DIE operated in a reference center. TVUS was performed pre-operatively
      by a trained or/and untrained ultrasound operator to search for DIE and rectal
      involvement. During surgery, DIE was diagnosed according to macroscopic and
      histological criteria. Sensitivity (Se), specificity (Sp) and c-index were
      calculated with 95% confidence intervals for trained and untrained operators, if
      TVUS results were significantly predictive of DIE and rectal involvement at
      p<0.05. RESULTS: 115 patients were included: 100 (87%) had DIE and 34 (29.6%) had
      bowel involvement. TVUS was performed by a trained ultrasound operator for 70
      patients and by an untrained one for 56 patients. When performed by a trained
      operator, TVUS significantly predicted DIE with a Se of 58% (95% CI, 46-70), a Sp
      of 87.5% (95% CI, 63-100) and a c-index of 0.73 (95% CI, 0.59-0.87). TVUS
      performed by an untrained operator was not significantly predictive of DIE
      (p=0.58). Rectal involvement was significantly predicted by TVUS performed by a
      trained operator with a Se of 40% (95% CI, 23-59), a Sp of 93% (95% CI, 86-100)
      and a c-index of 0.67 (95% CI, 0.56-0.77). None of the untrained ultrasound
      operators diagnosed a bowel involvement. CONCLUSION: TVUS is not sufficient to
      diagnose DIE and bowel involvement, in particular when performed by untrained
      ultrasound operators.

PMID- 29654938
TI  - Single port laparoscopy (SPL): Retrospective study evaluating postoperative pain
      in comparison with conventional laparoscopy (CL).
AB  - OBJECTIVE: To compare postoperative pain after single port laparoscopy (SPL)
      approach with conventional laparoscopy (CL) in case of adnexectomy. MATERIAL AND
      METHODS: This is a retrospective monocentric study involving patients who
      underwent adnexal surgery by SPL or CL for a suspected benign disease or as a
      preventive measure. The main outcome measure was the level of postoperative pain.
      RESULTS: A total of 87 patients were enrolled. Within 2h, the numerical scale
      (NS) was 1.9 in SPL group and 2.0 in the CL group (P=0.85). The next day, the NS
      was 1.8 in SPL group and 1.5 in CL group (P=0.55). The operating time was
      significantly shorter in SPL group (33 versus 56min, 95% CI [-31; -15], P<0.001)
      and no rupture of ovarian cysts occurred in this group. There was no significant
      difference concerning complications, length of hospital stay, general
      satisfaction and POSAS (Patient and Observer Scar Assessment Scale) score.
      CONCLUSION: This study confirms the feasibility of single-port laparoscopic
      adnexectomy. We have not shown significant difference in postoperative pain but
      the operating time was significantly reduced under the guise of an experienced
      surgeon.

PMID- 29654940
TI  - A technique for safe aspiration of an adnexal cyst during laparoscopy.

PMID- 29654941
TI  - Surgery using plasma energy for deep endometriosis: A quality of life assessment.
AB  - OBJECTIVE: The principal objective of our study was to assess women's quality of
      life (QoL) after surgery for Deep Endometriosis (DE), according to the surgical
      technique used. MATERIAL AND METHODS: Qualitative single-center survey in the
      department of obstetrics and gynecology, Angers University Hospital Center,
      France. All women who underwent surgery for DE from January 2011 to December 2015
      were contacted by phone. The Endometriosis Health Profile-5 score was used to
      assess QoL before and after the surgery. Fifty-two women (response rate=86%) were
      included and classified into 3 groups according to the surgical technique used:
      simple shaving, shaving exclusively or in part by plasma vaporization (plasma),
      and resection. RESULTS: The 3 groups were comparable for surgical history,
      preoperative QoL score, and characteristics of endometriotic lesions (size and
      site). All DE symptoms and QoL scores improved significantly after the surgery,
      all techniques combined (P<0.01). QoL scores for women who had plasma shaving or
      complete resection were significantly higher than those for women with simple
      shaving (respectively, 375 [225-800] and 450 [-50 to 725] vs 275 [-100 to 600];
      P=0.04). Self-image significantly improved only in the plasma group (P=0.03). The
      complete resection group had longer hospitals stays than the other groups
      (P=0.001), as well as a higher surgical revision rate (23% vs 0%; P=0.02).
      CONCLUSION: Plasma and complete resection improved QoL similarly for women with
      DE, both more than shaving alone. The advantage of plasma vaporization lies in
      the lesser morbidity and better self-image, both better than in women with
      resection.

PMID- 29654942
TI  - Exploring fetal response to acidosis in ewes: Choosing an adequate experimental
      model.
AB  - INTRODUCTION: Knowledge of fetal physiology during labor has been largely
      generated from animal models. Our team recently developed a new index to assess
      parasympathetic activity using different experimental protocols to obtain
      acidosis. The objective of the present study was to discuss the different
      protocols and to review other models proposed in the literature. MATERIAL AND
      METHODS: Pregnant ewes underwent a surgical procedure at the 123+/-2 days
      gestational age (term=145 days). Three experimental protocols were used: protocol
      A consisted of 25%, 50% and 75% umbilical cord occlusion (UCO) for 20min.
      Protocol B consisted of partial 75% UCO until reaching a pH<7.10. Protocol C
      consisted of brief, repetitive complete occlusion until severe acidosis occurred.
      Hemodynamic and blood gas parameters were compared to those of the stability
      period before UCO. RESULTS: Protocol A led to a progressive response depending on
      the degree of occlusion (decrease in fetal heart rate, arterial hypertension and
      pH). Protocol B led to severe acidosis, although the duration of UCO varied per
      animal. Protocol C also progressively led to acidosis. We observed high inter
      individual variability in the acidosis response. CONCLUSION: Pregnant ewes are a
      relevant model for exploring fetal response to acidosis. The frequency of UCO and
      partial or complete occlusion should be adapted to the expected effects.
      Knowledge of these protocols is important to respect ethical guidelines and to
      reduce the required number of animals. Moreover, it is important to consider the
      high individual variability of the acidosis response in the interpretation of the
      results.

PMID- 29654943
TI  - Acyl donors for native chemical ligation.
AB  - Native chemical ligation (NCL) has become one of the most important methods in
      chemical syntheses of proteins. Recently, in order to expand its scope,
      considerable effort has been devoted to tuning the C-terminal acyl donor
      thioesters used in NCL. This article reviews the recent advances in the design of
      C-terminal acyl donors, their precursors and surrogates, and highlights some
      noteworthy progress that may lead the future direction of protein chemical
      synthesis.

PMID- 29654944
TI  - Perinatal alpha-tocopherol overload programs alterations in kidney development
      and renal angiotensin II signaling pathways at birth and at juvenile age:
      Mechanisms underlying the development of elevated blood pressure.
AB  - alpha-Tocopherol (alpha-Toc) overload increases the risk of dying in humans (E.R.
      Miller III et al. Meta-analysis: high-dosage vitamin E supplementation may
      increase all-cause mortality Ann Int Med. 142 (2005) 37-46), and overload during
      early development leads to elevation of blood pressure at adult life, but the
      mechanism(s) remains unknown. We hypothesized that alpha-Toc overload during
      organogenesis affects the renal renin angiotensin system (RAS) components and
      renal Na+ handling, culminating with late elevated blood pressure. Pregnant
      Wistar rats received alpha-Toc or the superoxide dismutase mimetic tempol
      throughout pregnancy. We evaluated components of the intrarenal renin angiotensin
      system in neonate and juvenile offspring: Ang II-positive cells, Ang II receptors
      (AT1 and AT2), linked protein kinases, O2- production, NADPH oxidase abundance,
      lipid peroxidation and activity of Na+-transporting ATPases. In juvenile
      offspring we followed the evolution of arterial blood pressure. Neonates from
      alpha-Toc and tempol mothers presented with accentuated retardment in tubular
      development, pronounced decrease in glomerular Ang II-positive cells and AT1/AT2
      ratio, intense production of O2- and upregulation of the alpha, epsilon and
      lambda PKC isoforms. alpha-Toc decreased or augmented the abundance of renal
      (Na++K+)ATPase depending on the age and alpha-Toc dose. In juvenile rats the
      number of Ang II-positive cells returned to control values as well as PKCalpha,
      but co-existing with marked upregulation in the activity of (Na++K+) and Na+
      ATPase and elevated arterial pressure at 30 days. We conclude that the mechanisms
      of these alterations rely on selective targeting of renal RAS components through
      genic and pro-oxidant effects of the vitamin.

PMID- 29654946
TI  - Diagnostic contribution of HLA-A,B,C,DR genotyping in inflammatory joint disease.

PMID- 29654945
TI  - FOXO1 inhibition potentiates endothelial angiogenic functions in diabetes via
      suppression of ROCK1/Drp1-mediated mitochondrial fission.
AB  - Diabetes-induced endothelial cell (EC) dysfunction and neovascularization
      impairment constitute vascular complications with limited treatment regimens.
      Transcription factor FOXO1 is a key angiogenic regulator and plays a pathologic
      role in progression of diabetes. The present study was designed to determine the
      involvement of FOXO1 in impaired EC function and post-ischemic neovascularization
      in diabetes and investigate underlying mechanisms. We found that FOXO1-selective
      inhibitor AS1842856 improved blood flow recovery and capillary density in
      ischemic hindlimb, and rescued the delay of wound closure with a concomitant
      augmentation of mean perfusion rate in diabetic mice. In vitro, treatment with
      AS1842856 or FOXO1 siRNA abrogated high glucose-induced apoptosis and ameliorated
      capillary tube formation in human umbilical vein endothelial cells (HUVECs).
      FOXO1 inhibition relieved alterations in mitochondrial networks and significantly
      suppressed the overproduction of mitochondrial reactive oxygen species (mtROS)
      induced by high glucose in ECs. Expression of dynamin-related protein-1 (Drp1)
      and phosphorylation at Ser616, a protein required for mitochondrial fission, were
      enhanced by hyperglycemia, which could be neutralized by FOXO1 inhibition.
      Moreover, the transcription of Rho-associated coiled-coil containing protein
      kinase 1 (ROCK1), which phosphorylates Drp1 at Ser616, was shown by luciferase
      assay to be directly regulated by FOXO1. These findings suggested that FOXO1 is
      critical to preserve mitochondrial quantity and function in ECs, and FOXO1 may
      serve as a therapeutic target for microvascular complications of diabetes.

PMID- 29654947
TI  - 2018 update of French recommendations on the management of postmenopausal
      osteoporosis.
AB  - OBJECTIVES: To update the 2012 recommendations on pharmacotherapy for
      postmenopausal osteoporosis, under the aegis of the Bone Task Force of the French
      Society for Rheumatology (SFR) and of the Osteoporosis Research and Information
      Group (GRIO), in collaboration with scientific societies (College national des
      generalistes enseignants, College national des gynecologues et obstetriciens
      francais, Federation nationale des colleges de gynecologie medicale, Groupe
      d'etude de la menopause et du vieillissement hormonal, Societe francaise de
      chirurgie orthopedique, Societe francaise d'endocrinologie, and Societe francaise
      de geriatrie et de gerontologie). METHODS: Updated recommendations were developed
      by a task force whose members represented the medical specialties involved in the
      management of postmenopausal osteoporosis. The update was based on a literature
      review and developed using the method advocated by the French National Authority
      for Health (HAS). DISCUSSION AND CONCLUSION: The updated recommendations place
      strong emphasis on the treatment of women with severe fractures, in whom the use
      of osteoporosis medications is recommended. All the available osteoporosis
      medications are suitable in patients with severe fractures; zoledronic acid
      deserves preference as the fist-line drug after a hip fracture. In patients with
      or without non-severe fractures, the decision to use osteoporosis medications is
      based on bone mineral density values and in challenging cases, on probabilities
      supplied by prediction tools such as FRAX(r). All osteoporosis medications are
      suitable; raloxifene should be reserved for patients at low risk for peripheral
      fractures. The fracture risk should be reevaluated every 2 to 3 years to decide
      on the best follow-up treatment. These updated recommendations discuss the
      selection of first-line osteoporosis medications and treatment sequences.

PMID- 29654948
TI  - Gut microbiome and bone.
AB  - The gut microbiome is now viewed as a tissue that interacts bidirectionally with
      the gastrointestinal, immune, endocrine and nervous systems, affecting the
      cellular responses in numerous organs. Evidence is accumulating of gut microbiome
      involvement in a growing number of pathophysiological processes, many of which
      are linked to inflammatory responses. More specifically, data acquired over the
      last decade point to effects of the gut microbiome on bone mass regulation and on
      the development of bone diseases (such as osteoporosis) and of inflammatory joint
      diseases characterized by bone loss. Mice lacking a gut microbiome have bone mass
      alteration that can be reversed by gut recolonization. Changes in the gut
      microbiome composition have been reported in mice with estrogen-deficiency
      osteoporosis and have also been found in a few studies in humans. Probiotic
      therapy decreases bone loss in estrogen-deficient animals. The effect of the gut
      microbiome on bone tissue involves complex mechanisms including modulation of
      CD4+T cell activation, control of osteoclastogenic cytokine production and
      modifications in hormone levels. This complexity may contribute to explain the
      discrepancies observed betwwen some studies whose results vary depending on the
      age, gender, genetic background and treatment duration. Further elucidation of
      the mechanisms involved is needed. However, the available data hold promise that
      gut microbiome manipulation may prove of interest in the management of bone
      diseases.

PMID- 29654949
TI  - Relevance and feasibility of a systematic screening of multimorbidities in
      patients with chronic inflammatory rheumatic diseases.
AB  - OBJECTIVES: EULAR recently proposed to screen multimorbidities in chronic
      inflammatory rheumatic diseases. The aims of the study were to define the most
      common multimorbidities in chronic inflammatory rheumatic diseases, compare the
      screening approach performed in the clinic with the recent EULAR recommendations,
      validate the points to consider for the systematic standardized multimorbidity
      screening proposed by EULAR and assess feasibility of such a screening in a daily
      clinic. METHODS: Data were collected prospectively during a 1-day multimorbidity
      clinic. Diabetes, hypertension, CVD damage, chronic respiratory diseases,
      osteoporosis and preventive measures were assessed. The comparison with EULAR
      points to consider was performed retrospectively. RESULTS: We included 200
      consecutive patients (157 with rheumatoid arthritis, 37 spondyloarthritis, and 6
      connective tissue diseases or vasculitis). The most common multimorbidities
      already diagnosed in our patients were hypertension (26%) and diabetes (7.5%).
      Screening showed that 61.5% (CI95%: 54.6%-67.9%) patients presented at least one
      undiagnosed or uncontrolled diseases: diabetes (6%), hypertension (20.6%),
      dyslipidemia (16.1%) valvulopathies (16.8%), peripheral artery disease (4.5%);
      carotid stenosis (6.5%) and aortic aneurysm (5.5%). Overall, 39.9% patients had
      incomplete cancer screening and 52.8% incomplete vaccine schedule. Undiagnosed
      pulmonary obstruction and risk of sleep apnea were suspected in 15.5% and 40.1%
      patients, respectively. CONCLUSION: This study underlines the relevance of a
      systematic screening of multimorbidities in chronic inflammatory rheumatic
      diseases and its feasibility in a 1-day clinic. Spirometry and sleep apnea
      screening should be added to EULAR points to consider. The long-term impact of
      such screening needs to be evaluated.

PMID- 29654950
TI  - Effectiveness and safety of anakinra in gout patients with stage 4-5 chronic
      kidney disease or kidney transplantation: A multicentre, retrospective study.
AB  - OBJECTIVES: Interleukin (IL)-1beta blocking is effective for the treatment of
      gout flares and is recommended in patients with contraindications to the standard
      of care, such as stage 4-5 chronic kidney disease (CKD) patients. However,
      efficacy and safety data regarding these agents are lacking in this population.
      We aimed to investigate the efficacy and safety of anakinra for the treatment of
      gout flares in patients with stage 4-5 CKD or renal transplantation. METHODS:
      This retrospective study encompassing 3 academic centres included consecutive
      patients with stage 4-5 CKD or kidney transplantation who received anakinra for
      the treatment of acute gouty arthritis and completed at least one follow-up
      visit. Efficacy, occurrence of infection, and renal function variations were
      recorded. RESULTS: Of the 31 included patients (24 men, mean age 72+/-11 years),
      25 were non-transplant subjects with stage 4-5 CKD (mean estimated glomerular
      filtration rate, MDRD formula (eGFR) 22.7+/-6.5mL/min/1.73m2), and six had
      undergone kidney transplantation (mean eGFR 41.5+/-22.8mL/min/1.73m2). Median
      gout duration was 3.5 years, and the mean serum urate (SUA) level was 8.7mg/dL.
      Twenty-one (68%) patients had tophi, and 21 had gout arthropathy. Anakinra was
      efficacious in all patients (final VAS 10 and CRP level 10mg/L). Ten patients
      (32%) were anakinra dependent (i.e., required prolonged treatment with anakinra).
      A serious infection was recorded in only one patient, occurring 3 months after
      starting anakinra. No significant variation in renal function was observed.
      CONCLUSION: Anakinra may be a safe therapeutic option for gout patients with
      advanced CKD. Further randomized controlled studies are required to confirm our
      results.

PMID- 29654951
TI  - Residential risk factors for childhood pneumonia: A cross-sectional study in
      eight cities of China.
AB  - BACKGROUND: Children's pneumonia is a heavy health burden. Few studies have been
      carried out on residential risk factors for pneumonia in children. Potential
      risks associated with dwelling characteristics are still unknown. METHODS: A
      cross-sectional study was conducted among children in 8 cities in China during
      2010-2011 and 41,176 valid data on children aged 3-8 years old were used in this
      analysis. To obtain the lifetime-ever incidence of pneumonia in children and
      identify associations between pneumonia and residential risk factors, chi-square
      analysis and logistic regression methods were employed. Adjusted odds ratios were
      used as measures of effect with a 95% confidence interval. Confounding variables
      in the regression model include children's gender, birthweight, breastfeeding
      duration, parental smoking and family history of atopy. RESULTS: The average
      lifetime-ever incidence of childhood pneumonia was 32.3%. Urban children (33.6%)
      had more pneumonia than suburban (29.9%) and rural children (24.9%). More
      residential risk factors were found in urban-dwellings. Boys, low birthweight
      (<2500 g), breastfeeding duration <6 months, family allergic history, and
      exposure to parental smoking were found to be associated with higher pneumonia
      lifetime-ever incidences. Various indicators of dampness, including visible mold
      spots, damp stains, water damage, water condensation, damp clothing or bedding
      and mold odor, were also positively associated with pneumonia. Pneumonia
      incidence increased as the number of dampness indicators increased. Both natural
      gas and solid cooking fuels were positively associated with pneumonia compared
      with electricity. Compared with cement, construction materials including
      synthetic fiber, laminated wood, real wood, paint, emulsion paint and wall paper
      were positively associated with pneumonia. Daily living habits such as putting
      bedding to sunshine frequently and cleaning the child's bedroom every day could
      be effective preventive strategies. A dose-response relationship between the
      number of residential risk factors and pneumonia was observed when the risk
      factors number ranged from 7 to 11. Residences with more risk factors had higher
      lifetime-ever pneumonia odds ratios. CONCLUSIONS: Indoor environmental factors
      including dampness, use of solid fuels or natural gas for cooking and use of new
      construction materials are risk factors for childhood pneumonia. This study gives
      evidence for the importance of home environment exposures in the occurrence of
      childhood pneumonia. Actions against the residential risk factors described in
      this study may help to prevent pneumonia in children.

PMID- 29654952
TI  - The physical and cellular conditions of the human pulmonary circulation enable
      thrombopoiesis.
AB  - Animal evidence that platelet production occurs in the lungs is growing. We have
      investigated whether there is evidence to support pulmonary platelet production
      from studies using human conditions. We documented the presence of megakaryocytes
      (MKs) in the human pulmonary circulation and analyzed the role of the vascular
      microenvironment on MK function. Our results suggest that the endothelial
      microenvironment favors platelet formation and that von Willebrand factor
      combined with appropriate physical forces in flowing blood are determinant for
      platelet release. We also demonstrate that MKs have the potential to change
      ploidy as they circulate. These findings demonstrate a new pathophysiological
      environment affecting platelet production and provide new targets for therapeutic
      intervention.

PMID- 29654953
TI  - Effect of Subthalamic Deep Brain Stimulation on Upper Limb Dexterity in Patients
      with Parkinson Disease.
AB  - OBJECTIVE: The efficacy of deep brain stimulation (DBS) of the subthalamic
      nucleus (STN) on dexterity remains controversial despite its recognition as an
      effective strategy for Parkinson disease. The present study investigated the
      efficacy of STN-DBS for ameliorating bradykinesia and dexterity compared with
      dopaminergic medications. METHODS: Part III of the Unified Parkinson's Disease
      Rating Scale was used for the evaluation of bradykinesia, whereas the Purdue
      Pegboard Test and the Box and Block test were selected for dexterity. RESULTS:
      Our findings indicate that bradykinesia is significantly improved with both DBS
      and dopaminergic medication, whereas dexterity is improved only with DBS.
      Dopaminergic medication did not show a satisfactory efficacy on dexterity, and
      there was little synergistic effect of dopaminergic medication and STN-DBS for
      improving dexterity associated with Parkinson disease. CONCLUSIONS: Our results
      suggest that DBS is potentially more effective than dopaminergic medications for
      improving dexterity. The disparities in efficacy for bradykinesia and dexterity
      between DBS and dopaminergic medication hint at the potential mechanisms of STN
      DBS. We speculate that DBS follows at least 2 different mechanisms for improving
      parkinsonian symptoms: 1) the dopaminergic system, primarily for the improvement
      of bradykinesia and 2) the nondopaminergic system, for the improvement of
      dexterity. This hypothesis requires further verification and investigation.

PMID- 29654954
TI  - A New Minimally Invasive Technique for Primary Unstable C2 Spondylolysis in an 8
      Year-Old Child: A Case Report and Review of the Literature.
AB  - BACKGROUND: Posterior arch defect of C2 with an unstable spondylolysis is a rare
      condition mostly occurring within children. Its management is still
      controversial. CASE DESCRIPTION: We report in this article the first minimally
      invasive surgery (MIS) technique for this condition in an 8-year-old boy. A
      primary unstable C2 spondylolysis was diagnosed on the exploration of episodic
      paresthesia of upper limbs associated with headache lasting for several months.
      The surgical technique consisted in a direct pars repair through an MIS approach:
      METRx tubular retractor system (Medtronic Sofamor Danek, Memphis, Tennessee,
      USA), intraoperative C-arm fluoroscopy, surgical microscope, endoscopic spine
      instrument, and high-speed drill were required. Muscles were split and retracted.
      One-year postoperative course was excellent. CONCLUSIONS: After reviewing the
      past literature of this pathology, we discuss the minimally invasive posterior
      approach of the upper cervical spine. It is the first case, to our knowledge,
      describing direct minimally invasive repair for bilateral primary C2 pars defect
      in a child. Image guidance and surgical microscope help safe and effective screw
      placement.

PMID- 29654955
TI  - Histologic Features and Prognosis of Spinal Intradural Extramedullary Ewing
      Sarcoma: Case Report, Literature Review, and Analysis of Prognosis.
AB  - BACKGROUND: Ewing sarcoma is a malignant neoplasm that primarily involves
      extremity long bones, the pelvis, and soft tissues of children. The intradural
      extramedullary space is an uncommon location for Ewing sarcoma, and there is
      therefore a paucity of information regarding the features and natural history of
      this particular presentation. There is controversy regarding preoperative
      diagnosis, surgical management, and postoperative care, and there are no accepted
      standards. METHODS: Herein we present a 61-year-old man with an L1-3 intradural
      extramedullary Ewing sarcoma who underwent gross total resection of the tumor via
      laminectomy. Pathologic analysis revealed a diagnosis of Ewing sarcoma based on
      the characteristic immunohistochemistry and the presence of EWSR1-FLI1 fusion
      transcript by reverse-transcription polymerase chain reaction. RESULTS: There
      have been 28 cases of intradural extramedullary Ewing sarcoma reported in the
      literature. Out of 29 cases including the current case, 18 cases (62.1%) were
      men. The median and mean ages were 32 and 34.0 years, respectively, with a peak
      age group of 10-20 years. Twenty-two of 29 (72.4%) cases involved the lumbar
      spine, followed by the cervical spine (n = 7, 24.1%). Long-term prognosis was
      poor, with 1-, 2-, 3-, and 5-year progression-free survival rate of 75.0%, 56.3%,
      37.5%, and 18.8%, respectively. The 1-, 2-, 3-, and 5-year overall survival rate
      was 89.5%, 80.5%, 80.5%, and 43.0%, respectively. CONCLUSIONS: Herein, we present
      imaging and pathologic findings of the case with review of the literature.

PMID- 29654957
TI  - Cerebral Microbleeds Could Be Independently Associated with Intracranial Aneurysm
      Rupture: A Cross-Sectional Population-Based Study.
AB  - OBJECTIVE: To determine whether the presence of cerebral microbleeds (CMBs) is
      independently associated with intracranial aneurysm rupture and to identify the
      time interval of CMB-related intracranial aneurysm rupture. METHODS: This cross
      sectional study included 1847 patients with unruptured and ruptured intracranial
      aneurysms from January 2010 to November 2017. Clinical records and imaging,
      including T2-weighted gradient-recalled echo sequence magnetic resonance imaging
      that identified the presence of CMBs preoperatively, were evaluated. Univariate
      analysis and multivariate logistic regression were done to determine which
      parameters were independent factors for aneurysm rupture. The time interval of
      CMB-related intracranial aneurysm rupture was also evaluated. RESULTS: CMBs
      confirmed by magnetic resonance imaging were present in 142 patients (142/1847;
      7.7%). Of 142 patients with CMBs, 56 patients (including 17 ruptured aneurysms)
      who received endovascular treatment and another 86 consecutive patients who did
      not receive embolization or surgery for various reasons were followed for 3-49
      months. The incidence of CMB-related intracranial aneurysm rupture was 27.9%
      (24/86) during the follow-up period. The time interval of CMB-related
      intracranial aneurysm rupture was 3-27 months (median 9.5 months). Multivariate
      analyses showed CMBs were significantly correlated with intracranial aneurysm
      rupture (odds ratio = 1.6; 95% confidence interval, 1.1-2.4; P = 0.010).
      CONCLUSIONS: CMBs were independently associated with intracranial aneurysm
      rupture. Patients with CMBs have a 60% increased risk of aneurysm rupture
      compared with patients without CMBs.

PMID- 29654956
TI  - Comparison of Zero-profile Device Versus Plate-and-Cage Implant in the Treatment
      of Symptomatic Adjacent Segment Disease after Anterior Cervical Discectomy and
      Fusion: A Minimum 2-Year Follow-Up Study.
AB  - OBJECTIVE: The purpose of this study was to compare the clinical efficacy of
      anterior cervical discectomy and fusion (ACDF) with Zero-profile device (Zero-p)
      and traditional cervical plate-and-cage implant in the treatment of symptomatic
      adjacent segment disease (ASD) and to determine the optimal reoperation
      procedure. METHODS: This was a retrospective study of 58 patients with
      symptomatic ASD after an initial ACDF surgery and who had undergone a reoperation
      with ACDF with Zero-p (n = 27) and cervical plate-and-cage (n = 31) at our
      medical center between January 2010 and December 2015. RESULTS: The Japanese
      Orthopaedic Association score, Neck Disability Index score, Visual Analog Scale
      score, C2-C7 Cobb angle, and disc height index demonstrated significant
      improvements compared with the preoperative in both Zero-p and plate-and-cage
      groups (P < 0.05). However, there were no differences between the two groups (P >
      0.05). The reoperation time for the Zero-p group (83.4 +/- 18.9 min) was less
      than that for the plate-and-cage group (96.5 +/- 20.1 min), with significant
      difference (P < 0.05). Five patients (8.6%) had cage subsidence, and 14 patients
      (24.1%) had dysphagia after the reoperation. There was no statistical
      significance in the difference between the 2 groups in cage subsidence (P >
      0.05). However, the incidence of dysphagia in the plate-and-cage group (38.7%)
      was higher than in the Zero-p group (7.4%), with a significant difference (P <
      0.05). CONCLUSIONS: ACDF with Zero-p obtaining the same surgical efficacy,
      compared with traditional cervical plate-and-cage, can significantly shorten the
      reoperation time and reduce the incidence of postoperative dysphagia. This option
      may be preferable for symptomatic patients with ASD qualifying for the anterior
      approach, in terms of biomechanics and surgical outcomes.

PMID- 29654958
TI  - The Survival Effect of Repeat Surgery at Glioblastoma Recurrence and its Trend: A
      Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Glioblastoma (GBM) is a dismal disease managed in the first instance
      by surgical resection, temozolomide, and radiation. The role of repeat surgery at
      recurrence remains ill defined. This study aims to quantify the effect of repeat
      surgery in recurrent GBM on overall survival and determine if a trend in reported
      effect over time exists. METHODS: Searches of 7 electronic databases from
      inception to January 2018 were conducted following PRISMA (Preferred Reporting
      Items for Systematic reviews and Meta-Analyses) guidelines. There were 2692
      articles identified for screening. Prognostic hazard ratios (HRs) derived from
      multivariate regression analysis were extracted and analyzed using meta-analysis
      of proportions and linear regression. RESULTS: Eight observational studies
      reporting prognostic HRs in 10 cohorts were included. They described 1906
      recurrent GBM diagnoses, managed by surgery at primary diagnosis, with 709 (37%)
      undergoing further repeat surgery at recurrence. Repeat surgery was shown to
      confer a statistically significant survival advantage compared with no surgery at
      recurrence in the pooled cohort (HR, 0.722; P < 0.001). Newer studies trended
      toward a more superior prognostic advantage of repeat surgery compared with
      earlier studies (effect coefficient, 0.856; P = 0.012). CONCLUSIONS: This meta
      analysis of contemporary literature suggests that repeat surgery at GBM
      recurrence in select patients confers a significant, prognostic overall survival
      advantage independent of other prognostic factors. Furthermore, newer studies are
      significantly more likely to suggest greater benefit than are older studies. The
      main limitation is the selection bias inherent in the cohorts pooled for
      analysis. Larger prospective randomized controlled studies are needed to validate
      the findings of this study and provide stratification for such benefit justified
      by quality of life metrics.

PMID- 29654959
TI  - A Small Glossopharyngeal Schwannoma Presenting with Intractable Vomiting: Case
      Presentation and Literature Review.
AB  - BACKGROUND: Glossopharyngeal schwannomas are rare tumors. Clinical and radiologic
      presentation closely resembles those of vestibular schwannomas. Their clinical
      presentation varies from vestibulocochlear dysfunction to glossopharyngeal and
      vagal nerve dysfunction. CASE DESCRIPTION: We report a case of a small
      glossopharyngeal schwannoma presenting with intractable recurrent sudden episodes
      of vomiting that subsided after tumor resection. To our knowledge, this is the
      only case in the literature of glossopharyngeal schwannoma presenting with nerve
      irritation in the form of intractable emesis. CONCLUSIONS: Small glossopharyngeal
      schwannomas can present with irritative symptoms of the ninth cranial nerve
      causing vomiting refractory to medical treatment. Intracranial imaging should be
      considered in the investigation of unexplained intractable vomiting even if the
      gross neurologic examination is normal.

PMID- 29654960
TI  - Challenges of Managing Patients with Symptomatic Large Traumatic Cervical
      Pseudomeningoceles.
AB  - BACKGROUND: Traumatic cervical pseudomeningoceles (TCPs) occur secondary to
      traction of the cervical nerve roots resulting in violation of the dura. Surgical
      repair is not necessary in most cases because pseudomeningoceles have a high
      propensity to spontaneously resolve with conservative management alone.
      Currently, there are a limited number of cases of large TCPs (large is defined as
      >=6 cm in greatest diameter), and there is no established guideline for the
      management of such lesions. CASE DESCRIPTION: We describe the cases of 2 young
      men in their 20s who were involved in a motor vehicle accident. Both patients
      suffered a brachial plexus injury and developed large TCPs. Patient 1 was treated
      surgically for TCP using a combined intra-/extradural approach using a fascia
      lata graft. Patient 2 was ultimately treated nonsurgically because a spontaneous
      resolution of the pseudomeningocele was achieved over the period of 7 months
      after the accident. Both patients underwent brachial plexus repair surgery
      consisting of spinal accessory nerve transfer to the suprascapular nerve and
      intercostal nerve transfer to the musculocutaneous nerve. CONCLUSIONS: Disease
      progression of TCPs is a dynamic process, and even large lesions may
      spontaneously resolve without surgical intervention. When surgery is indicated, a
      definitive dural repair using a fascia lata graft to cover the dural tear intra-
      and extradurally is an effective method. Surgery must be planned carefully on a
      case-by-case basis, and close follow-up with thorough physical examination and
      serial imaging is critical to monitor disease progression.

PMID- 29654961
TI  - Airborne non-contact and contact broadband ultrasounds for frequency attenuation
      profile estimation of cementitious materials.
AB  - In this paper, the study of frequency-dependent ultrasonic attenuation in
      strongly heterogeneous cementitious materials is addressed. To accurately
      determine the attenuation over a wide frequency range, it is necessary to have
      suitable excitation techniques. We have analysed two kinds of ultrasound
      techniques: contact ultrasound and airborne non-contact ultrasound. The
      mathematical formulation for frequency-dependent attenuation has been established
      and it has been revealed that each technique may achieve similar results but
      requires specific different calibration processes. In particular, the airborne
      non-contact technique suffers high attenuation due to energy losses at the air
      material interfaces. Thus, its bandwidth is limited to low frequencies but it
      does not require physical contact between transducer and specimen. In contrast,
      the classical contact technique can manage higher frequencies but the measurement
      depends on the pressure between the transducer and the specimen. Cement specimens
      have been tested with both techniques and frequency attenuation dependence has
      been estimated. Similar results were achieved at overlapping bandwidth and it has
      been demonstrated that the airborne non-contact ultrasound technique could be a
      viable alternative to the classical contact technique.

PMID- 29654962
TI  - Proposed Chaoyang vascular classification for superior mesenteric-portal vein
      invasion, resection, and reconstruction in patients with pancreatic head cancer
      during pancreaticoduodenectomy - A retrospective cohort study.
AB  - BACKGROUND: Patients with pancreatic head cancer involving the superior
      mesenteric-portal vein can benefit from vascular resection and reconstruction. We
      aimed to propose our vascular classification and assess its effect in this study.
      MATERIAL AND METHODS: Data of consecutive patients, who were diagnosed with
      pancreatic head cancer, and underwent radical pancreaticoduodenectomy combined
      with superior mesenteric-portal vein resection and reconstruction at our
      institute between October 2013 and August 2016, were retrospectively collected.
      On a scale of one to four, our classification was proposed. Perioperative
      parameters were then analyzed among the four types. RESULTS: There were a total
      of 52 patients with 11 in type I, 15 in type II, 18 in type III, 8 in type IV.
      The respective operative time and estimated blood loss of types III (425-990 min,
      265-1820 mL) and IV (480-1036 min, 330-1690 mL) were greater than those of types
      I (300-824 min, 200-1255 mL) and II (369-875 min, 305-1400 mL) (p < 0.05). Type
      IV had larger tumors (4-7 cm) than type I (1.5-4 cm) (p < 0.05). Percentage of
      tunica intima involvement and the median survival time of type I (9.1%, 22
      months) were lower and longer than those of types II (46.7%, 17 months) and III
      (44.4%, 16 months; p < 0.05), and even lower and longer than those of type IV
      (87.5%, 10 months; p < 0.01), respectively. CONCLUSIONS: Our classification can
      provide a system to grade patients with venous invasion in order of surgical
      difficulty and survival.

PMID- 29654963
TI  - The pretreatment thrombocytosis as one of prognostic factors for gastric cancer:
      A systematic review and meta-analysis.
AB  - BACKGROUND & AIMS: At present, increasing reports have shown that pretreatment
      platelet count was associated with the prognosis of many types of cancer. We
      performed rounded analysis to comprehensively analyze and evaluate the prognostic
      significance of pretreatment thrombocytosis for patients with gastric cancer.
      METHODS: We identified relevant studies by searching database including PubMed,
      Embase, Cochrane Library and Web of Science. The relative risk (RR) with its 95%
      confidence interval (CI) was used to assess the correlation between
      thrombocytosis and overall survival (OS) of gastric cancer patients. We also
      conducted subgroup analysis and sensitivity analysis for the prognostic effect of
      thrombocytosis on OS. The analysis was performed and assessed using Review
      Manager 5.2. RESULTS: A total of nine studies including 7158 participants were
      included in this systematic review. Analysis results showed that pretreatment
      thrombocytosis had a close relationship with 1, 3 and 5 years survival of gastric
      cancer, with the pooled RRs being 0.80 (95% CI 0.71-0.90; P = 0.0004), 0.65 (95%
      CI 0.45-0.92; P = 0.02) and 0.64 (95% CI 0.47-0.87; P = 0.004) respectively.
      CONCLUSIONS: The present rounded analysis suggests that pretreatment
      thrombocytosis may have significant association with poor survival of patients
      with gastric cancer.

PMID- 29654964
TI  - Adjuvant systemic therapy and postoperative outcomes after resection of node
      positive gallbladder cancer.

PMID- 29654965
TI  - Endothelial nitric oxide synthase gene polymorphisms and risk of erectile
      dysfunction: An updated meta-analysis of genetic association studies.
AB  - PURPOSE: Endothelial nitric oxide synthase (eNOS) polymorphisms have been
      implicated as risk factors for erectile dysfunction (ED), but the results of
      genetic association studies are inconclusive. We performed a meta-analysis of
      published studies investigating the association between ED and three eNOS
      polymorphisms, intron 4 VNTR, G894T and T786C in humans. METHODS: The PubMed, Web
      of Science, CNKI and Google Scholar databases were searched for relevant studies
      published up to November 2017. Association studies with case-control design were
      included. For each study with genotype information we calculated odds ratios (OR)
      and 95% confidence intervals (CI). RESULTS: The search identified 13 eligible
      studies. The G894T and T786C polymorphisms showed a significant association with
      ED risk in Caucasians (GT + TT versus GG for G894T: OR = 2.13, 95% CI = 1.08
      4.19; CC versus CT + TT for T786C: OR = 3.29, 95% CI = 2.30-4.72) and Asians (GT
      + TT versus GG for G894T: OR = 2.08, 95% CI = 1.53-2.84; CC + CT versus TT for
      T786C: OR = 3.13, 95% CI = 1.35-7.25). In addition, the intron 4 VNTR
      polymorphism was associated with ED risk only among Caucasian subjects (aa versus
      bb + ab: OR = 2.38, 95% CI = 1.15-4.93). We found no evidence of publication
      bias. The robustness of overall analyses was ensured in sensitivity analyses
      excluding studies deviating from Hardy-Weinberg equilibrium. CONCLUSION: Our
      findings suggest that common genetic polymorphisms in the eNOS gene contribute to
      risk of ED, presumably by effects on eNOS activity and NO availability.

PMID- 29654966
TI  - Reply letter to: Letter to the editor on the article " Adjuvant systemic therapy
      and postoperative outcomes after resection of node positive gallbladder cancer".

PMID- 29654967
TI  - Conversion surgery for gastric cancer: A cohort study from a western center.
AB  - BACKGROUND: Advanced unresectable gastric cancer has a dismal prognosis. The aim
      of this study was to evaluate the short- and long-term outcomes of patients who
      underwent induction chemotherapy +/- gastrectomy for advanced gastric cancer.
      MATERIAL AND METHODS: All patients referred to our center with a clinical
      diagnosis of unresectable locally advanced or stage IV gastric adenocarcinoma
      between April 2005 and August 2016 were included in the study. Cox regression was
      performed to find independent prognostic factor among the considered variable.
      RESULTS: The cohort included 73 patients: 16 had best supportive care, 35
      chemotherapy alone and 22 chemotherapy plus radical surgery. Thirty-three
      patients underwent surgery after chemotherapy. Twenty-two patients had R0
      surgery, while the remaining 11 had only an exploratory procedure. Nine patients
      (40.9%) underwent gastrectomy plus hyperthermic intraperitoneal chemotherapy.
      Three patients out of 22 developed postoperative complications with a Clavien
      Dindo grade above 2. Median survival was 50 months for patients who had
      chemotherapy plus surgery while it was 14 and 3 for those who had chemotherapy
      alone and best supportive care, respectively (p < 0.0001). Cox regression
      analysis performed on the whole cohort identified only radical conversion surgery
      as an independent factor positively associated with survival (HR 0.12, 95% CI
      0.05-0.29, p < 0.0001). CONCLUSION: Conversion gastrectomy, when R0 could be
      achieved, is associated with long survivals and it is the most important
      prognostic factor in patients with advanced gastric cancer. Further studies are
      needed to define the ideal patient who can really benefit from this treatment.

PMID- 29654968
TI  - Mini-incision versus hand-assisted laparoscopic donor nephrectomy in living-donor
      kidney transplantation: A retrospective cohort study.
AB  - BACKGROUND: Increasing use of Living Donor Kidney Transplantation (LDKT) would
      decrease the discrepancy between patients awaiting transplantation and organ
      availability. Minimally invasive surgical approaches attempt to improve outcomes
      and foster living donation. This report compares outcomes of open minimal
      incision nephrectomy (Mini N) and a hand assisted laparoscopic nephrectomy
      (HALN). METHODS: This is a retrospective analysis of a prospectively maintained
      clinical database of LDKT using HALN or Mini N at a single institution between
      July 2007 and December 2015. Donor and recipient demographics, relevant pre-,
      intra- and post-operative factors, outcomes such as patient and graft survival
      rates, and complications were evaluated. RESULTS: Four hundred and fifty-four
      adult LDKT (243 Mini N, 211 HALN) were performed during the study period.
      Recipient and donor demographics were comparable except for higher BMI (p =
      0.027) in HALN donors. One-, 3- and 5-year patient and graft survival rates were
      comparable. Six HALN donors experienced infectious wound complications or
      superficial skin dehiscence; none did in the Mini N group (p = 0.009). Eight HALN
      donors and one Mini N donor required an incisional hernia repair (p = 0.014).
      Recipients had similar warm ischemia times (33 v. 35 min, p = 0.491), but
      recipient surgeons of HALN nephrectomies subjectively noted higher anastomotic
      difficulty (10.4% v. 4.5%, p = 0.0183). Other parameters were similar between
      groups. CONCLUSION: Both Mini N and HALN provide similar long term recipient and
      donor outcomes. Offering techniques such as Mini N and HALN for living donor
      kidney procurement facilitates the opportunity to provide living donors safer and
      better tolerated nephrectomy procedures.

PMID- 29654969
TI  - Assessing associations of anaemia with morbidity and mortality following liver
      transplantation.

PMID- 29654970
TI  - Efficient co-conversion process of chicken manure into protein feed and organic
      fertilizer by Hermetia illucens L. (Diptera: Stratiomyidae) larvae and functional
      bacteria.
AB  - A chicken manure management process was carried out through co-conversion of
      Hermetia illucens L. larvae (BSFL) with functional bacteria for producing larvae
      as feed stuff and organic fertilizer. Thirteen days co-conversion of 1000 kg of
      chicken manure inoculated with one million 6-day-old BSFL and 109 CFU Bacillus
      subtilis BSF-CL produced aging larvae, followed by eleven days of aerobic
      fermentation inoculated with the decomposing agent to maturity. 93.2 kg of fresh
      larvae were harvested from the B. subtilis BSF-CL-inoculated group, while the
      control group only harvested 80.4 kg of fresh larvae. Chicken manure reduction
      rate of the B. subtilis BSF-CL-inoculated group was 40.5%, while chicken manure
      reduction rate of the control group was 35.8%. The weight of BSFL increased by
      15.9%, BSFL conversion rate increased by 12.7%, and chicken manure reduction rate
      increased by 13.4% compared to the control (no B. subtilis BSF-CL). The residue
      inoculated with decomposing agent had higher maturity (germination index >92%),
      compared with the no decomposing agent group (germination index ~86%). The
      activity patterns of different enzymes further indicated that its production was
      more mature and stable than that of the no decomposing agent group. Physical and
      chemical production parameters showed that the residue inoculated with the
      decomposing agent was more suitable for organic fertilizer than the no
      decomposing agent group. Both, the co-conversion of chicken manure by BSFL with
      its synergistic bacteria and the aerobic fermentation with the decomposing agent
      required only 24 days. The results demonstrate that co-conversion process could
      shorten the processing time of chicken manure compared to traditional compost
      process. Gut bacteria could enhance manure conversion and manure reduction. We
      established efficient manure co-conversion process by black soldier fly and
      bacteria and harvest high value-added larvae mass and biofertilizer.

PMID- 29654972
TI  - Mammal responses to the human footprint vary across species and stressors.
AB  - A rapidly expanding human footprint - comprised of anthropogenic land-use change
      and infrastructure - is profoundly affecting wildlife distributions worldwide.
      Cumulative effects management (CEM) is a regional approach that seeks to manage
      combined effects of the human footprint on biodiversity across large spatial
      scales. Challenges to implementing this approach include a lack of ecological
      data at large spatial scales, the high cost of monitoring multiple indicators,
      and the need to manage multiple footprints across industries. To inform
      development of effective CEM, we used large mammals as indicators to address the
      following questions: a) do species respond more strongly to individual footprint
      features or to cumulative effects (combined area of all footprint types, measured
      as total footprint), b) which features elicit the strongest responses across
      species, and c) are the direction of responses to footprint consistent? We used
      data from 12 years of snowtrack surveys (2001-2013) in the boreal forest of
      Alberta, coupled with regional footprint and landcover data, to develop
      generalized linear mixed-effects models relating the relative abundance of five
      boreal mammals [gray wolf (Canis lupus), Canada lynx (Lynx canadensis), coyote
      (Canis latrans), white-tailed deer (Odocoileus virginianus) and moose (Alces
      alces)] to individual and cumulative effects of the human footprint. We found
      that across species the strongest responses were to agriculture, roads, and young
      cutblocks (<10 years), suggesting these as potential priority stressors to
      address within CEM. Most species also responded to total footprint, indicating
      that in the absence of detailed information on individual features, this coarse
      measure can serve as an index of cumulative effects. There was high variability
      in direction and magnitude of responses across species, indicating that community
      level responses are likely and should be considered within CEM planning.

PMID- 29654971
TI  - Agricultural implications of providing soil-based constraints on urban expansion:
      Land use forecasts to 2050.
AB  - Urbanization onto adjacent farmlands directly reduces the agricultural area
      available to meet the resource needs of a growing society. Soil conservation is a
      common objective in urban planning, but little focus has been placed on targeting
      soil value as a metric for conservation. This study assigns commodity and water
      storage values to the agricultural soils across all of the watersheds in
      Michigan's Lower Peninsula to evaluate how cities might respond to a soil
      conservation-based urbanization strategy. Land Transformation Model (LTM)
      simulations representing both traditional and soil conservation-based
      urbanization, are used to forecast urban area growth from 2010 to 2050 at five
      year intervals. The expansion of urban areas onto adjacent farmland is then
      evaluated to quantify the conservation effects of soil-based development. Results
      indicate that a soil-based protection strategy significantly conserves total
      farmland, especially more fertile soils within each soil type. In terms of
      revenue, ~$88 million (in current dollars) would be conserved in 2050 using soil
      based constraints, with the projected savings from 2011 to 2050 totaling more
      than $1.5 billion. Soil-based urbanization also increased urban density for each
      major metropolitan area. For example, there were 94,640 more acres directly
      adjacent to urban land by 2050 under traditional development compared to the soil
      based urbanization strategy, indicating that urban sprawl was more tightly
      contained when including soil value as a metric to guide development. This study
      indicates that implementing a soil-based urbanization strategy would better
      satisfy future agricultural resource needs than traditional urban planning.

PMID- 29654973
TI  - A green and sustainable approach on statistical optimization of laccase mediated
      delignification of sugarcane tops for enhanced saccharification.
AB  - Bioethanol production from lignocellulosic biomass is a promising approach
      towards finding an alternative for transportation fuels that is driven by the
      prerequisite to lessen our dependency on fossil fuels, increase energy security
      and mitigate greenhouse gas emission. Recalcitrance of lignocellulosic biomass is
      a major hindrance in bioethanol production. Hence, an efficient pretreatment
      method is necessary for degradation of lignin and providing accessibility of
      holocellulose for hydrolysis. In an attempt to overcome this bottleneck, laccase
      mediated delignification of sugarcane tops was studied using central composite
      design (CCD) based on response surface methodology (RSM). The effect of different
      process parameters such as temperature, pH, solid loading, enzyme titre and
      incubation time were evaluated. It was observed that under optimum conditions of
      pH 7, solid loading of 21% (w/v), enzyme titre of 430.3 IU/mL, temperature of 40 
      degrees C and incubation of 6 h, maximum delignification of 79.1% was achieved.
      Compositional analysis, energy density measurement and water retention capacity
      of the biomass was also conducted along with GC-MS analysis for identification of
      low molecular compounds formed during delignification. Structural
      characterization of the biomass before and after pretreatment process were
      analysed by Scanning Electron Microscopy (SEM), Fourier-Transform Infra-Red
      Spectroscopy (FTIR) and X-Ray Diffraction Spectroscopy (XRD) that further
      substantiated the delignification of sugarcane tops.

PMID- 29654974
TI  - A new methodology for royalties distribution of the Itaipu hydroelectric plant:
      The hydrographic basin as the unit of analysis.
AB  - Over the past few years, many sectors such as energy generation, industry,
      domestic supply, and agriculture have encountered serious environmental problems
      due to the lack of rainfall. Thus, the purpose of this paper is to review the
      current methodology of royalties distribution from Itaipu hydroelectric plant. In
      the proposed approach, two criteria were considered to establish the division of
      Itaipu royalties: (1) the relative percentage of the water flow in the generation
      of electricity and, (2) the relative percentage of the drop in the height of
      water. 62 hydroelectric plants were evaluated in this study. In 52 plants the
      water flow was the factor that most contributed to the generation of electricity.
      In 2013, 346 municipalities benefited the Itaipu royalties. With the proposed
      methodology, 1,327 municipalities will receive the resource, what would increase
      the revenue of each of these municipalities by, on average, US$ 87,436.91 per
      year. The methodology presented herein proposes a reduction in the environmental
      disparity that now exists in Brazil, through improvement to Government
      instruments and environmental policies. The distribution of royalties throughout
      the watershed can provide additional resources to support payment programs for
      environmental services at the state and municipality levels.

PMID- 29654975
TI  - Detection of retromer assembly in Plasmodium falciparum by immunosensing coupled
      to Surface Plasmon Resonance.
AB  - Retromer complex plays a crucial role in intracellular protein trafficking and is
      conserved throughout the eukaryotes including malaria parasite, Plasmodium
      falciparum, where it is partially conserved. The assembly of retromer complex in
      RBC stages of malarial parasite is extremely difficult to explore because of its
      complicated physiology, small size, and intra-erythrocytic location. Nonetheless,
      understanding of retromer assembly may pave new ways for the development of novel
      antimalarials targeting parasite-specific protein trafficking pathways. Here, we
      investigated the assembly of retromer complex in P. falciparum, by an
      immunosensing method through highly sensitive Surface Plasmon Resonance (SPR)
      technique. After taking leads from the bioinformatics search and literature,
      different interacting proteins were identified and specific antibodies were
      raised against them. The sensor chip was prepared by covalently linking antibody
      specific to one component and the whole cell lysate was passed through it in
      order to trap the interacting complex. Antibodies raised against other
      interacting components were used to detect them in the trapped complex on the SPR
      chip. We were able to detect three different components in the retromer complex
      trapped by the immobilized antibody specific against a different component on a
      sensor chip. The assay was reproduced and validated in a different two-component
      CD74-MIF system in mammalian cells. We, thus, illustrate the assembly of retromer
      complex in P. falciparum through a bio-sensing approach that combines SPR with
      immunosensing requiring a very small amount of sample from the native source.

PMID- 29654976
TI  - Mechanism of irreversible inhibition of Mycobacterium tuberculosis shikimate
      kinase by ilimaquinone.
AB  - Ilimaquinone (IQ), a marine sponge metabolite, has been considered as a potential
      therapeutic agent for various diseases due to its broad range of biological
      activities. We show that IQ irreversibly inactivates Mycobacterium tuberculosis
      shikimate kinase (MtSK) through covalent modification of the protein.
      Inactivation occurred with an apparent second-order rate constant of about 60 M-1
      s-1. Following reaction with IQ, LC-MS analyses of intact MtSK revealed covalent
      modification of MtSK by IQ, with the concomitant loss of a methoxy group,
      suggesting a Michael-addition mechanism. Evaluation of tryptic fragments of IQ
      derivatized MtSK by MS/MS demonstrated that Ser and Thr residues were most
      frequently modified with lesser involvement of Lys and Tyr. In or near the MtSK
      active site, three residues of the P-loop (K15, S16, and T17) as well as S77,
      T111, and S44 showed evidence of IQ-dependent derivatization. Accordingly,
      inclusion of ATP in IQ reactions with MtSK partially protected the enzyme from
      inactivation and limited IQ-based derivatization of K15 and S16. Additionally,
      molecular docking models for MtSK-IQ were generated for IQ-derivatized S77 and
      T111. In the latter, ATP was observed to sterically clash with the IQ moiety. Out
      of three other enzymes evaluated, lactate dehydrogenase was derivatized and
      inactivated by IQ, but pyruvate kinase and catalase-peroxidase (KatG) were
      unaffected. Together, these data suggest that IQ is promiscuous (though not
      entirely indiscriminant) in its reactivity. As such, the potential of IQ as a
      lead in the development of antitubercular agents directed against MtSK or other
      targets is questionable.

PMID- 29654977
TI  - Identification of Isomeric Aspartate residues in betaB2-crystallin from Aged
      Human Lens.
AB  - Many post-translational modifications such as oxidation, deamidation and
      isomerization of amino acid residues occur in lens proteins with aging. One such
      modification, isomerization of aspartate in lens alpha-crystallin, has been well
      studied by amino acid enantiomer analysis and LC-MS/MS. LC-MS/MS can quickly and
      easily identify D- and L-amino acid-containing peptides without purification of
      lens protein mixtures. However, this method has a weak point in that isomeric
      peptides of major components are detected predominantly, while those from minor
      proteins such as beta- and gamma-crystallins have not been fully determined.
      Therefore, the isomerization of amino acid residues in beta- and gamma-crystallin
      families has been little studied. To solve those problems and detect the
      isomerization of Asp residues in lens betaB2-crystallin, the main component of
      the beta-crystallin family, here we have developed steps for sample fractionation
      before d/l analysis based on either LC-MS/MS or amino acid derivatization to
      diastereoisomers followed by RP-HPLC. To capture a small amount of peptide, a
      multiple reaction monitoring (MRM) method based on quadrupole MS/MS (Q-MS) was
      applied to the water-soluble fraction of whole lens. The d/l analysis based on
      both LC-MS/MS and diastereoisomer formation showed the presence of multiple
      isomerization sites, including Asp4, Asp83, Asp92 and Asp192, in betaB2
      crystallin in aged lens. These isomerization sites were confirmed to exist in an
      age-dependent manner by Q-MS. Synthetic peptides of betaB2-crystallin containing
      different isomers of Asp showed differential elution profiles during RP-HPLC,
      indicating differences in the local structure or hydrophobicity of Asp-isomer
      containing peptides. These results suggest that the isomerization sites are
      distributed on exposed regions of betaB2-crystallin and thus likely to have an
      impact on crystallin subunit-subunit interactions, induce abnormal crystallin
      aggregation, and contribute to senile cataract formation in aged lens.

PMID- 29654979
TI  - Attachment in action-changing the face of 21st century couple therapy.
AB  - The field of couple therapy-one of the most widely sought and practiced modality
      of therapy-has been revolutionized by the emergence of attachment science in the
      21st century. We now understand not only the centrality of close relationships
      for human health and wellbeing, but also that the key to a healthy happy
      relationship is a secure attachment bond. Emotionally Focused Therapy is an
      attachment-based approach that aims to help couples create a secure attachment
      bond. Several outcome studies have shown that EFT helps to not only alleviate
      relationship distress but individual co-morbidities as well, with positive follow
      up effects. EFT appears to help couples not only improve their relationships but
      also access the optimal resilience and wellbeing secure attachment allows.

PMID- 29654978
TI  - Proteomic approach and expression analysis revealed the differential expression
      of predicted leptospiral proteases capable of ECM degradation.
AB  - Leptospira, the causative agent of leptospirosis is known to have many proteases
      with potential to degrade extracellular matrix. However, a multipronged approach
      to identify, classify, characterize and elucidate their role has not been
      attempted. Our proteomic approach using high-resolution LC-MS/MS analysis of
      Triton X-114 fractions of Leptospira interrogans resulted in the identification
      of 104 proteases out of 130 proteases predicted by MEROPS. In Leptospira
      approximately 3.5% of the genome complements for proteases, which include
      catalytic types of metallo-, serine-, cysteine-, aspartic-, threonine- and
      asparagine- peptidases. Comparison of proteases from different serovars revealed
      that M04, M09B, M14A, M75, M28A, A01 and U73 protease families are exclusively
      present in pathogenic form. The M23 and S33 protease families are represented
      with >14 members in Leptospira. The differential expression under physiological
      temperature (37  degrees C) and osmolarity (300 mOsM) showed that proteases
      belonging to the catalytic type of Metallo-peptidases are upregulated
      significantly in pathogenic conditions. In silico prediction and characterization
      of the proteases revealed that several proteases are membrane anchored and
      secretory, classical as well as non-classical system. The study demonstrates the
      diversity and complexity of proteases, while maintaining conservation across the
      serovars in Leptospira and their differential expression under pathogenic
      conditions.

PMID- 29654980
TI  - Hypnosis Enhances the Effects of Pain Education in Patients With Chronic
      Nonspecific Low Back Pain: A Randomized Controlled Trial.
AB  - : The potential benefits of combining pain education (PE) with clinical hypnosis
      (CH) has not yet been investigated in individuals with chronic pain. A total of
      100 patients with chronic nonspecific low back pain were randomized to receive
      either: 1) PE alone, or 2) PE with CH. Outcomes were collected by a blinded
      assessor at 2 weeks and 3 months after randomization. The primary outcomes were
      average pain intensity, worst pain intensity (both assessed with 11-point numeric
      rating scales), and disability (24-item Roland Morris Disability Questionnaire)
      at 2 weeks. At 2 weeks, participants who received PE with CH reported lower worst
      pain intensity (mean difference = 1.35 points, 95% confidence interval [CI] = .32
      2.37) and disability (mean difference = 2.34 points, 95% CI = .06-4.61), but not
      average pain intensity (mean difference = .67 point, 95% CI = -.27 to 1.62),
      relative to participants who received PE alone. PE with CH participants also
      reported more global perceived benefits at 2 weeks (mean difference = -1.98
      points, 95% CI = -3.21 to -.75). At 3 months, participants who received PE with
      CH reported lower worst pain intensity (mean difference = 1.32 points, 95% CI =
      .29-2.34) and catastrophizing (mean difference = 5.30 points, 95% CI = 1.20
      9.41). No adverse effects in either treatment condition were reported. To our
      knowledge, this is the first trial showing that additional use of hypnosis with
      PE results in improved outcomes over PE alone in patients with chronic
      nonspecific low back pain. PERSPECTIVE: This study provides evidence supporting
      the efficacy of another treatment option for teaching patients to self-manage
      chronic low back pain that has a relatively low cost and that can be offered in
      groups.

PMID- 29654981
TI  - Urinary metabolomics study on the anti-inflammation effects of flavonoids
      obtained from Glycyrrhiza.
AB  - Rheumatoid arthritis (RA) is a chronic disease with pain, swelling, and
      limitation in the motion and function of multiple joints thus leading to high
      disability. Previous studies have shown that flavonoids and saponins are the most
      abundant and active constituents in Glycyrrhiza, which possess a wide range of
      pharmacological effects such as anti-inflammatory, antioxidant and anti-bacteria.
      But the mechanisms of those actions are not entirely clear. In order to clarify
      the mechanisms of those actions, the pharmacodynamical assessments of extraction
      of water-soluble components and flavonoids and saponins obtained from Glycyrrhiza
      were investigated. Combining the pharmacodynamical researches, we found that
      flavonoids obtained from Glycyrrhiza had more significant therapeutic effects on
      acute inflammation, chronic inflammation and inflammatory pain than that of
      extraction of water-soluble components and saponins obtained from Glycyrrhiza.
      The results indicated that flavonoids are the main medicinal ingredients in
      Glycyrrhiza. In order to further investigate the mechanism of the action of
      flavonoids in Glycyrrhiza on treating RA, a urine metabolomics method based on
      ultra high-performance liquid chromatography coupled with quadrupole time-of
      flight mass spectrometry (UPLC-Q-TOF-MS) was established to observe the metabolic
      variations in adjuvant-induced arthritis (AIA) rats and investigate the
      therapeutic effect of flavonoids in Glycyrrhiza on RA. As a result, twenty
      potential biomarkers were found by comparison with the model group (MG) and
      flavonoid treated group (FG). We associated these compounds with related
      metabolic pathways, the results showed that these biomarkers were mainly
      associated with purine metabolism, taurine and hypotaurine metabolism, tryptophan
      metabolism, phenylalanine metabolism, tricarboxylic acid cycle (TCA cycle),
      pantothenate and coenzyme A (CoA) biosynthesis. The results about the
      pharmacodynamics and metabolomics provided a theoretical basis for clarifying the
      mechanism of flavonoids in Glycyrrhiza in the treatment of RA.

PMID- 29654982
TI  - Rapid characterization of the chemical constituents of Sijunzi decoction by UHPLC
      coupled with Fourier transform ion cyclotron resonance mass spectrometry.
AB  - Sijunzi decoction, a renowned Chinese prescription has long been utilized to
      treat gastrointestinal problems. In the context of this research work, the use of
      Ultra high performance liquid chromatography combined with Fourier transform ion
      cyclotron resonance mass spectrometry was made to separate and characterize the
      components of Sijunzi decoction. The performance of Liquid chromatography was
      carried out on a C8 column (150 mm * 2.1 mm, 1.8 MUm); moreover, the mobile phase
      were consisted of 0.2% formic acid (A) and acetonitrile (B). In accordance with
      the findings, characterization of 120 chemical compounds was performed by liquid
      chromatography with mass spectrometry. The key constituents among them included
      ginsenosides (in Radix Ginseng), 16 triterpene carboxylic acids (in Poria),
      sesquiterpenes (in Rhizoma Atractylodis Macrocephalae), triterpenesaponins (in
      Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle) as well as flavonoids (in
      Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle) in Sijunzi decoction. This
      research developed the bases for prospective research associated with Sijunzi
      decoction, together with being expected to be useful to rapidly extract and
      characterize the constituents in other Traditional Chinese herbal formulations.

PMID- 29654983
TI  - Effects of process parameters on the efficiency of chromatographic separations
      using a cuboid packed-bed device.
AB  - In recent papers we have proposed cuboid packed-bed devices as viable
      alternatives to preparative columns with low bed-height to diameter ratios that
      are typically used for biopharmaceutical purification processes. In this case
      study, we systematically examined operating parameters such as mobile phase flow
      rate, sample injection volume and feed protein concentration on the
      characteristics of flow-through and bound-and-eluted protein peaks. The current
      study was carried out using strong anion exchange media packed in a cuboid packed
      bed device and its equivalent column, i.e. with identical volume and bed-height.
      Our experimental results showed that the cuboid packed-bed device outperformed
      its equivalent column at all conditions examined. However, the improvement in
      performance in flow-through experiments was more significant at lower flow rates,
      and when smaller sample volumes (i.e. less than 20% of bed volume) were injected.
      Also, the performance of the cuboid packed-bed was significantly better when a
      concentrated protein sample was injected using a small volume loop. In bind-and
      elute experiments, the flow rate had a very significant impact on the performance
      of the cuboid packed-bed device, with better results being obtained at the lower
      flow rates examined. By choosing appropriate experimental conditions,
      significantly sharper peaks and thereby efficient separations could be achieved
      using the cuboid packed-bed device than with its equivalent column.

PMID- 29654984
TI  - The investigation of immunoprotective and sedative hypnotic effect of total
      polysaccharide from Suanzaoren decoction by serum metabonomics approach.
AB  - Suanzaoren decoction, as one of the traditional Chinese medicine prescriptions,
      has been most commonly used in Asian countries and reported to inhibit the
      process of immunodeficiency insomnia. Polysaccharide is important component which
      also contributes to the role of immunoprotective and sedative hypnotic effects.
      This study was aimed to explore the immunoprotective and sedative hypnotic
      mechanisms of polysaccharide from Suanzaoren decoction by serum metabonomics
      approach. With this purpose, complex physical and chemical immunodeficiency
      insomnia models were firstly established according to its multi-target property.
      Serum samples were analyzed using UHPLC/Q-TOF-MS spectrometry approach to
      determine endogenous metabolites. Then, principal component analysis was used to
      distinguish the groups, and partial least squares discriminate analysis was
      carried out to confirm the important variables. The serum metabolic profiling was
      identified and pathway analysis was performed after the total polysaccharide
      administration. The twenty-one potential biomarkers were screened, and the levels
      were all reversed to different degrees in the total polysaccharide treated
      groups. These potential biomarkers were mainly related to vitamin, sphingolipid,
      bile acid, phospholipid and acylcarnitine metabolisms. The result has indicated
      that total polysaccharide could inhibit insomnia triggered by immunodeficiency
      stimulation through regulating those metabolic pathways. This study provides a
      useful approach for exploring the mechanism and evaluating the efficacy of total
      polysaccharide from Suanzaoren decoction.

PMID- 29654986
TI  - Progression of calcific aortic valve sclerosis in WHHLMI rabbits.
AB  - BACKGROUND AND AIMS: Aortic valve stenosis (AS) is the most common valvular heart
      disease and can be life-threatening. The pathogenesis of aortic valve
      calcification remains largely unknown, primarily due to the lack of an adequate
      animal model. The high-cholesterol diet-induced AS model in rabbits is one of the
      established models, but it has the significant limitation of liver dysfunction
      leading to low survival rates. We hypothesized that a myocardial infarction-prone
      Watanabe heritable hyperlipidemic (WHHLMI) rabbit, an animal model of familial
      hypercholesterolemia and atherosclerosis, is a useful animal model of AS.
      METHODS: WHHLMI rabbits, aged 20 months and 30 months (n = 19), and control
      Japanese White rabbits (n = 4), aged 30 months, were used and evaluated by
      echocardiography under anesthesia. Pathological evaluation and quantitative
      analyses by polymerase chain reaction (PCR) were also performed. RESULTS: The
      lipid profile was similar between 20 months and 30 months. Two rabbits died due
      to spontaneous myocardial infarction during the study. Thirty-month-old WHHLMI
      rabbits exhibited significantly smaller aortic valve area (0.22 +/- 0.006 cm2vs.
      0.12 +/- 0.01 cm2, p < 0.05) and higher maximal transvalvular pressure gradient
      (7.0 +/- 0.32 vs. 9.9 +/- 0.95 mmHg, p < 0.05) than 20 month-old rabbits.
      Macroscopic examination of excised aortic valves demonstrated thickened and
      degenerated valve leaflets at 30 months. Histological evaluation confirmed
      thickened leaflets with calcified nodules at 30 months. Real-time PCR of resected
      aortic valve also showed increased expression level of calcification-related
      molecules including osteopontin, Sox9, Bmp2, RANKL, osteoprotegerin, and Runx2 (p
      < 0.05 each) in 30-month-old rabbits. CONCLUSIONS: WHHLMI rabbits may be useful
      models of early-stage AS in vivo.

PMID- 29654985
TI  - Summary of the 2017 Alcohol and Immunology Research Interest Group (AIRIG)
      meeting.
AB  - On June 24, 2017, the 22nd annual Alcohol and Immunology Research Interest Group
      (AIRIG) meeting was held as a satellite conference during the annual Research
      Society on Alcoholism (RSA) Scientific Meeting in Denver, Colorado. The 2017
      meeting focused broadly on mechanisms that link alcohol to tissue injury and
      inflammation, and how this research can be translated to improve human health.
      Two plenary sessions composed the meeting, which first explored the association
      between alcohol and trauma/tissue injury, and finished with a discussion of
      alcohol and mucosal inflammation. The presentations encompassed diverse areas of
      alcohol research, from effects on the brain, to airway and pulmonary systems, to
      gut barrier disruption. The discussions also thoughtfully highlighted how current
      laboratory and clinical research can be used to prevent or treat alcohol-related
      morbidity and mortality.

PMID- 29654987
TI  - Ecological momentary assessment of contextual variables, satisfaction, and
      emotional and behavioral states of adolescents by level of victimization.
AB  - The harmful effects of victimization on mental health have been demonstrated in
      several age groups, cultures, and populations, but there is wide variability in
      the resulting psychopathology. Ecological momentary assessment (EMA) allows the
      expression of an emotional state to be recorded at any given time and linked to a
      situation or context. This study aimed to analyze the contextual variables
      (where, with whom, and what), momentary satisfaction, and perception of momentary
      emotional and behavioral symptoms in a cohort of adolescents by the level of
      victimization, using EMA. We explored the everyday symptom profiles and the
      contexts in which events took place among 100 adolescents over a one-week period.
      Sociodemographic data were collected and assessment was done using the EMA (as a
      smartphone application) and the Juvenile Victimization Questionnaire (to assess
      childhood and adolescent victimization). In this study, regarding contextual
      variables, the group with the highest level of victimization (top 10%) showed a
      significant relationship with being away from home and being with friends other
      than classmates, and not being with parents or relatives. There was also an
      unexpectedly higher frequency of sporting engagement in this group. A
      relationship existed between emotional and behavioral problems and higher levels
      of victimization. In conclusion, the different groups of victimized subjects
      present a relatively high level of satisfaction in relation to the daily contexts
      and show low levels of emotional and behavioral symptomatology.

PMID- 29654988
TI  - Assessment of the safety benefits of vehicles' advanced driver assistance,
      connectivity and low level automation systems.
AB  - The Connected Vehicle (CV) technologies together with other Driving Assistance
      (DA) technologies are believed to have great effects on traffic operation and
      safety, and they are expected to impact the future of our cities. However, few
      research has estimated the exact safety benefits when all vehicles are equipped
      with these technologies. This paper seeks to fill the gap by using a general
      crash avoidance effectiveness framework for major CV&DA technologies to make a
      comprehensive crash reduction estimation. Twenty technologies that were tested in
      recent studies are summarized and sensitivity analysis is used for estimating
      their total crash avoidance effectiveness. The results show that crash avoidance
      effectiveness of CV&DA technology is significantly affected by the vehicle type
      and the safety estimation methodology. A 70% crash avoidance rate seems to be the
      highest effectiveness for the CV&DA technologies operating in the real-world
      environment. Based on the 2005-2008 U.S. GES Crash Records, this research found
      that the CV&DA technologies could lead to the reduction of light vehicles'
      crashes and heavy trucks' crashes by at least 32.99% and 40.88%, respectively.
      The rear-end crashes for both light vehicles and heavy trucks have the most
      expected crash benefits from the technologies. The paper also studies the
      effectiveness of Forward Collision Warning technology (FCW) under fog conditions,
      and the results show that FCW could reduce 35% of the near-crash events under fog
      conditions.

PMID- 29654989
TI  - Perfusion-decellularization of human ear grafts enables ECM-based scaffolds for
      auricular vascularized composite tissue engineering.
AB  - INTRODUCTION: Human ear reconstruction is recognized as the emblematic enterprise
      in tissue engineering. Up to now, it has failed to reach human applications
      requiring appropriate tissue complexity along with an accessible vascular tree.
      We hereby propose a new method to process human auricles in order to provide a
      poorly immunogenic, complex and vascularized ear graft scaffold. METHODS: 12
      human ears with their vascular pedicles were procured. Perfusion
      decellularization was applied using a SDS/polar solvent protocol. Cell and
      antigen removal was examined by histology and DNA was quantified. Preservation of
      the extracellular matrix (ECM) was assessed by conventional and 3D-histology,
      proteins and cytokines quantifications. Biocompatibility was assessed by
      implantation in rats for up to 60 days. Adipose-derived stem cells seeding was
      conducted on scaffold samples and with human aortic endothelial cells whole graft
      seeding in a perfusion-bioreactor. RESULTS: Histology confirmed cell and antigen
      clearance. DNA reduction was 97.3%. ECM structure and composition were preserved.
      Implanted scaffolds were tolerated in vivo, with acceptable inflammation,
      remodeling, and anti-donor antibody formation. Seeding experiments demonstrated
      cell engraftment and viability. CONCLUSIONS: Vascularized and complex auricular
      scaffolds can be obtained from human source to provide a platform for further
      functional auricular tissue engineered constructs, hence providing an ideal road
      to the vascularized composite tissue engineering approach. STATEMENT OF
      SIGNIFICANCE: The ear is emblematic in the biofabrication of tissues and organs.
      Current regenerative medicine strategies, with matrix from donor tissues or 3D
      printed, didn't reach any application for reconstruction, because critically
      missing a vascular tree for perfusion and transplantation. We previously
      described the production of vascularized and cell-compatible scaffolds, from
      porcine ear grafts. In this study, we ---- applied findings directly to human
      auricles harvested from postmortem donors, providing a perfusable matrix that
      retains the ear's original complexity and hosts new viable cells after seeding.
      This approach unlocks the ability to achieve an auricular tissue engineering
      approach, associated with possible clinical translation.

PMID- 29654991
TI  - An electrospun fiber reinforced scaffold promotes total meniscus regeneration in
      rabbit meniscectomy model.
AB  - : Low vascularization in meniscus limits its regeneration ability after injury,
      and tissue engineering is the most promising method to achieve meniscus
      regeneration. In this study, we fabricated a kind of composite scaffold by
      decellularized meniscus extracellular matrix/polycaprolactone (DMECM/PCL)
      electrospinning fibers and porous DMECM, in which DMECM/PCL fibers were used as
      reinforcing component. The tensile modulus of the composite scaffold in
      longitudinal and crosswise directions were 8.5 +/- 1.9 and 2.3 +/- 0.3 MPa,
      respectively. Besides that, the DMECM/PCL electrospinning fibers enhanced suture
      resistance of the composite scaffold more than 5 times than DMECM scaffold
      effectively. In vitro cytocompatibility showed that the porous structure provided
      by DMECM component facilitated meniscus cells' proliferation. DMECM was also the
      main component to regulate cell behaviors, which promoted meniscus cells
      expressing extracellular matrix related genes such as COL I, COL II, SOX9 and
      AGG. Rabbits with total meniscectomy were used as animal model to evaluated the
      composited scaffolds performance in vivo at 3 and 6 months. Results showed that
      rabbits with scaffold implanting could regenerate neo-menisci in both time
      points. The neo-menisci had similar histology structure and biochemical content
      with native menisci. Although neo-menisci had inferior tensile modulus than
      native ones, its modulus was improved with implanting time prolonging. MRI
      imaging showed the signal of neo-meniscus in the body is clear, and X-ray imaging
      of knee joints demonstrated the implantation of scaffolds could relief joint
      space narrowing. Moreover, rabbits with neo-menisci had better cartilage
      condition in femoral condyle and tibial plateau compared than meniscectomy group.
      STATEMENT OF SIGNIFICANCE: We fabricated the meniscus scaffold by combining
      porous decellularized meniscus extracellular matrix (DMECM) and DMECM/PCL
      electrospinning fibers together, which used the porous structure of DMECM, and
      the good tensile property of electrospinning fibers. We believe single material
      cannot satisfy increasing needs of scaffold. Therefore, we combined not only
      materials but also fabrication methods together to develop scaffold to make good
      use of each part. DMECM in electrospinning fibers also made these two components
      possible to be integrated through crosslinking. Compared to existing meniscus
      scaffold, the composite scaffold had (1) soft structure and extrusion would not
      happen after implantation, (2) ability to be trimmed to suitable shape during
      surgery, and (3) good resistance to suture.

PMID- 29654990
TI  - Combinatorial approaches in post-polymerization modification for rational
      development of therapeutic delivery systems.
AB  - : The combinatorial polymer library approach has been proven to be effective for
      the optimization of therapeutic delivery systems. The library of polymers with
      chemical diversity has been synthesized by (i) polymerization of functionalized
      monomers or (ii) post-polymerization modification of reactive polymers. Most
      scientists have followed the first approach so far, and the second method has
      emerged as a versatile approach for combinatorial biomaterials discovery. This
      review focuses on the second approach, especially discussing the post
      modifications that employ reactive polymers as templates for combinatorial
      synthesis of a library of functional polymers with distinct structural diversity
      or a combination of different functionalities. In this way, the functional
      polymers have a consistent chain length and distribution, which allows for
      systematic optimization of therapeutic delivery polymers for the efficient
      delivery of genes, small-molecule drugs, and protein therapeutics. In this
      review, the modification of representative reactive polymers for the delivery of
      different therapeutic payloads are summarized. The recent advances in rational
      design and optimization of therapeutic delivery systems based on reactive
      polymers are highlighted. This review ends with a summary of the current
      achievements and the prospect on future directions in applying the approach of
      post-polymerization modification of polymers to accelerate the development of
      therapeutic delivery systems. STATEMENT OF SIGNIFICANCE: A strategy to rationally
      design and systematically optimize polymers for the efficient delivery of
      specific therapeutics is highly needed. The combinatorial polymer library
      approach could be an effective way to this end. The post-polymerization
      modification of reactive polymer precursors is applicable for the combinatorial
      synthesis of a library of functional polymers with distinct structural diversity
      across a consistent degree of polymerization. This allows for parallel comparison
      and systematic evaluation/optimization of functional polymers for efficient
      therapeutic delivery. This review summarizes the key elements of this
      combinatorial polymer synthesis approach realized by post-polymerization
      modification of reactive polymer precursors towards the development and
      identification of optimal polymers for the efficient delivery of therapeutic
      agents.

PMID- 29654992
TI  - Exploring the potential of polyurethane-based soft foam as cell-free scaffold for
      soft tissue regeneration.
AB  - : Reconstructive treatment after trauma and tumor resection would greatly benefit
      from an effective soft tissue regeneration. The use of cell-free scaffolds for
      adipose tissue regeneration in vivo is emerging as an attractive alternative to
      tissue-engineered constructs, since this approach avoids complications due to
      cell manipulation and lack of synchronous vascularization. In this study, we
      developed a biodegradable polyurethane-based scaffold for soft tissue
      regeneration, characterized by an exceptional combination between softness and
      resilience. Exploring the potential as a cell-free scaffold required profound
      understanding of the impact of its intrinsic physico-chemical properties on the
      biological performance in vivo. We investigated the effect of the scaffold's
      hydrophilic character, degradation kinetics, and internal morphology on (i) the
      local inflammatory response and activation of MGCs (foreign body response); (ii)
      its ability to promote rapid vascularisation, cell infiltration and migration
      through the scaffold over time; and (iii) the grade of maturation of the newly
      formed tissue into vascularized soft tissue in a murine model. The study revealed
      that soft tissue regeneration in vivo proceeded by gradual infiltration of
      undifferentiated mesenchymal cells though the periphery toward the center of the
      scaffold, where the rapid formation of a functional and well-formed vascular
      network supported cell viability overtime. STATEMENT OF SIGNIFICANCE: Exploring
      the potential of polyurethane-based soft foam as cell-free scaffold for soft
      tissue regeneration. In this work, we address the unmet need for synthetic
      functional soft tissue substitutes that provide adequate biological and
      mechanical support to soft tissue. We developed a series of flexible cross-linked
      polyurethane copolymer scaffolds with remarkable fatigue-resistance and tunable
      physico-chemical properties for soft tissue regeneration in vivo. Accordingly, we
      could extend the potential of this class of biomaterials, which was so far
      confined for bone and osteochondral tissue regeneration, to other types of
      connective tissue.

PMID- 29654993
TI  - Effects of upstream shear forces on priming of platelets for downstream adhesion
      and activation.
AB  - : Platelets in flowing blood are sometimes exposed to elevated shear forces
      caused by anastomotic stenosis at the blood vessel-vascular implant interface.
      The objective of this study was to determine how effective upstream shear forces
      are in priming platelets for downstream adhesion and activation. Flow chambers
      with upstream stenotic regions (shear rates of 400-1000 s-1) were manufactured by
      relief molding of polydimethylsiloxane. Downstream from the stenotic regions,
      microcontact printing was used to covalently immobilize three different proteins
      (fibrinogen, collagen, or von Willebrand factor) to serve as platelet capture
      agents. Anticoagulated whole blood was perfused through the flow chambers and
      platelet adhesion to the downstream capture region was quantified. It was found
      that transient exposure of platelets to increased shear forces resulted in higher
      platelet adhesion on all three proteins. The duration of the platelet exposure to
      elevated shear forces was varied by changing the length of the stenotic regions.
      The results indicated that, in addition to the magnitude of shear forces, the
      duration of exposure to these forces was also an important factor in priming
      platelets. The effect of upstream shear forces on platelet activation was
      assessed by quantifying P-selectin, integrin alphaIIbbeta3, lysosomal
      glycoprotein, and phosphatidylserine exposure using flow cytometry. The results
      suggested that increased shear forces were capable of increasing the priming of
      platelets for downstream activation. This study implicates the anastomotic
      region(s) of vascular implants as a locus of platelet pre-activation that may
      lead to thrombus formation downstream. STATEMENT OF SIGNIFICANCE: A synthetic
      small-diameter vascular graft can often become stenotic due to intimal fibrous
      hyperplasia, either generally along the inside of the graft or at the anastomotic
      regions, leading to an increased shear force on flowing platelets. Our lab is
      studying how the upstream platelet preactivation (aka "priming") in flowing blood
      affects their downstream adhesion and activation. This manuscript describes a
      study in which priming of platelets is achieved by upstream stenotic narrowing in
      a microfluidic flow chamber. Such experimental design was intended to mimic a
      vascular implant with stenotic upstream anastomosis and downstream exposed
      platelet protein agonists. Understanding how the pre-activated platelets respond
      to imperfect vascular implant surfaces downstream is an important factor in
      designing better vascular implants.

PMID- 29654995
TI  - Kinetic study of thermal degradation of olive cake based on a scheme of
      fractionation and its behavior impregnated of metals.
AB  - This research aims to provide a better knowledge of the thermal decomposition of
      the olive cake as well as this lignocellulosic material loaded, in a previous
      stage of biosorption, with heavy metals for its use in processes of energy
      recovery. Firstly, isolation of constituents of the olive cake was carried out.
      Then, experiments were performed by thermogravimetric analysis (TGA) and
      differential thermogravimetry (DTG) under inert and oxidative atmosphere at a
      heating rate of 15 K/min for each isolated fraction. Next, adequate reactions
      schemes were proposed to find kinetic parameters. Validation of these schemes
      were verified by the goodness of fitting between experimental and simulated data.
      Also, some important combustion characteristics such as ignition and burnout
      temperatures were determined. With regard to the effect of metals, cadmium,
      copper, chromium, nickel and lead present in metal-loaded olive cake did not
      modify values of kinetic parameters which described the thermal decomposition
      processes.

PMID- 29654994
TI  - Oral feeding practices and discharge timing for moderately preterm infants.
AB  - BACKGROUND: Oral feeding skills of moderately preterm infants are not mature at
      birth. AIMS: To establish the relationship between postmenstrual age at
      introduction of first oral feeding and attainment of full oral feeding and
      hospital discharge for moderately preterm infants. STUDY DESIGN: Multicenter
      retrospective analysis of a prospective cohort of moderately preterm infants
      admitted to a Eunice Kennedy Shriver National Institute of Child Health and Human
      Development Neonatal Research Network hospital. SUBJECTS: 6146 infants born at 29
      33 weeks' gestation from January 2012 to November 2013. OUTCOME MEASURES:
      Postmenstrual age at full oral feeding and at hospital discharge. RESULTS: The
      median postmenstrual age at first oral feeding was 33.9 weeks (interquartile
      range 33.1-34.3). For each week earlier at first oral feeding, full oral feeding
      occurred 4.5 days earlier (p < 0.0001) and hospital stay was shortened by 3.4
      days (p < 0.0001). Higher birth weight (p < 0.0001) and black maternal race (p =
      0.0001) were associated with younger postmenstrual age at full oral feeding and
      at discharge. CONCLUSION: Moderately preterm infants with earlier introduction of
      oral feeding achieved earlier full oral feeding and hospital discharge.

PMID- 29654996
TI  - Ultrasound-assisted in-situ transesterification of wet Aurantiochytrium sp. KRS
      101 using potassium carbonate.
AB  - A new in-situ transesterification method was developed for wet biomass: K2CO3 was
      used as an alkaline catalyst and, Aurantiochytrium sp. KRS 101 as oleaginous DHA
      producing microalgae. It was found that the presence of water greatly impaired
      the overall efficiency even with the powerful catalyst that had worked
      surpassingly well with dry biomass, and thus a mechanical aid like
      ultrasonication was needed to make advantage of full potential of the alkaline
      catalyst. The total fatty acid ethyl ester (FAEE) recovery yield of 94.6% was
      achieved with sonication at 100 g/L of biomass (40% moisture), 3% of K2CO3, 70 
      degrees C and 30 min. All these suggest that the ultrasound assisted in-situ
      transesterification can offer a feasible means for FAEE recovery and it was so by
      way of overcoming the physical limitation of mass transfer caused the presence of
      water and providing effective contacts between reactants.

PMID- 29654997
TI  - Promoting helix pitch and trichome length to improve biomass harvesting
      efficiency and carbon dioxide fixation rate by Spirulina sp. in 660 m2 raceway
      ponds under purified carbon dioxide from a coal chemical flue gas.
AB  - The helix pitch and trichome length of Spirulina sp. were promoted to improve the
      biomass harvesting efficiency and CO2 fixation rate in 660 m2 raceway ponds
      aerated with food-grade CO2 purified from a coal chemical flue gas. The CO2
      fixation rate was improved with increased trichome length of the Spirulina sp. in
      a raceway pond with double paddlewheels, baffles, and CO2 aerators (DBA raceway
      pond). The trichome length has increased by 33.3 MUm, and CO2 fixation rate has
      increased by 42.3% and peaked to 51.3 g/m2/d in a DBA raceway pond. Biomass
      harvesting efficiency was increased with increased helix pitch. When the day
      average greenhouse temperature was 33  degrees C and day-average sunlight
      intensity was 72,100 lu*, the helix pitch of Spirulina sp. was increased to 56.2
      MUm. Hence the biomass harvesting efficiency was maximized to 75.6% and biomass
      actual yield was increased to 35.9 kg in a DBA raceway pond.

PMID- 29654998
TI  - Improving hydrocarbon yield from catalytic fast co-pyrolysis of hemicellulose and
      plastic in the dual-catalyst bed of CaO and HZSM-5.
AB  - The high concentration of oxygenated compounds in pyrolytic products prohibits
      the conversion of hemicellulose to important biofuels and chemicals via fast
      pyrolysis. Herein a dual-catalyst bed of CaO and HZSM-5 was developed to convert
      acids in the pyrolytic products of xylan to valuable hydrocarbons. Meanwhile,
      LLDPE was co-pyrolyzed with xylan to supplement hydrogen during the catalysis of
      HZSM-5. The results showed that CaO could effectively transform acids into
      ketones. A minimum yield of acids (2.74%) and a maximum yield of ketones (42.93%)
      were obtained at a catalyst to feedstock ratio of 2:1. The dual-catalyst bed
      dramatically increased the yield of aromatics. Moreover, hydrogen-rich fragments
      derived from LLDPE promoted the Diels-Alder reactions of furans and participated
      in the hydrocarbon pool reactions of non-furanic compounds. As a result, a higher
      yield of hydrocarbons was achieved. This study provides a fundamental for
      recovering energy and chemicals from pyrolysis of hemicellulose.

PMID- 29654999
TI  - Biogas production and microbial community properties during anaerobic digestion
      of corn stover at different temperatures.
AB  - Temperature has different effects on anaerobic digestion (AD) of various
      biomasses, which could bring out changes in microbial communities. The
      relationship between microbial community and methane production at 35  degrees C
      (R35), 38  degrees C (R38), 41  degrees C (R41), and 44  degrees C (R44) was
      analyzed during AD of corn stover (CS). The results showed that the daily biogas
      and methane production from R44 were 16.6%-42.4% and 16.2%-40.6% higher than
      yields from R35, R38 and R41, respectively. The abundance of Bacteroidetes in
      R35, R38 and R41 was relatively close (30.70%-39.36%), which was low in R44
      (16.00%). The abundance of Firmicutes in R35 was 32.30%, however, Firmicutes was
      the most dominant phylum at R44 (66.58%). The abundance of
      Miscellaneous_Crenarchaeotic_Group and Euryarchaeota were 54.63 +/- 6.47% and
      44.43 +/- 6.73% across all digesters. This research demonstrated that among all
      temperatures studied, 44  degrees C could enhance the conversion efficiency of
      the substrates to methane and be recommended for better conversion of CS in AD
      process.

PMID- 29655000
TI  - Platelet activation and antiplatelet therapy in sepsis: A narrative review.
AB  - Platelet activation plays an important role in the development of sepsis. During
      sepsis, platelet activation leads to endothelial cell injury and promotes
      neutrophil extracellular trap and microthrombus formation, exacerbating septic
      coagulation and inflammatory reactions. The resultant induction or aggravation of
      disseminated intravascular coagulation (DIC) leads to organ damage. Antiplatelet
      drugs can inhibit coagulation and inflammatory reactions in models of sepsis,
      reducing damage to organ function. Clinical studies suggest that aspirin may
      improve the prognosis of patients with sepsis. In conclusion, antiplatelet drugs
      are promising agents that can improve the prognosis of sepsis patients and are
      expected to become a new line of treatment. However, further clinical studies are
      required for validation.

PMID- 29655001
TI  - Asian patients versus non-Asian patients in the efficacy and safety of direct
      oral anticoagulants relative to vitamin K antagonist for venous thromboembolism:
      A systemic review and meta-analysis.
AB  - INTRODUCTION: The standard for treatment and secondary prevention of venous
      thromboembolism (VTE) has been vitamin K antagonist (VKA), which might be
      associated with a higher risk of bleeding particularly in Asian patients. Direct
      oral anticoagulants (DOAC) have been shown to be safer alternatives for VTE. It
      remains unclear whether this is the case in Asian ethnicity. MATERIALS AND
      METHODS: We performed a meta-analysis of randomized controlled trials to evaluate
      the efficacy and safety of DOACs in Asian and non-Asian patients with acute VTE.
      We searched MEDLINE, CENTRAL, and ClinicalTrials.gov. The efficacy endpoint was
      recurrent VTE or VTE-related death. The safety endpoint was major bleedings or
      clinically relevant non-major bleedings. The pooled odds ratios (OR) and 95%
      confidence intervals (CI) were calculated. RESULTS: We identified 6 studies that
      comprised 3542 Asian and 23,481 non-Asian patients. The efficacy of DOACs was
      comparable with VKA in both Asian and non-Asian patients (OR, 0.90; 95% CI, 0.55
      1.49; P = 0.69 for Asian patients; OR, 0.92; 95% CI, 0.78-1.08; P = 0.32 for non
      Asian patients; P interaction = 0.94). DOACs significantly reduced the safety
      endpoint compared with VKA in Asian patients (OR, 0.64; 95% CI, 0.51-0.80; P <
      0.001), while DOACs were associated with non-significant reduction in non-Asian
      patients (OR, 0.73; 95% CI, 0.53-1.01; P = 0.06), indicating that the reduction
      seemed numerically more prominent in Asian patients, although there was no
      statistically significant interaction (P interaction = 0.49). CONCLUSIONS: The
      efficacy of DOACs was comparable with VKA irrespective of ethnicity, and DOACs
      could be safer alternatives in Asian patients.

PMID- 29655002
TI  - Structural changes of fibrinogen as a consequence of cirrhosis.
AB  - Cirrhosis is a disease which may develop as a consequence of various conditions.
      In advanced liver disease, blood coagulation can be seriously affected. Portal
      hypertension, vascular abnormalities and/or a dysbalance in coagulation factors
      may result in bleeding disorders or in the development of thrombosis. Fibrinogen
      is the main protein involved in clot formation and wound healing. The aim of this
      work was to analyse the glycosylation pattern of the isolated fibrinogen
      molecules by lectin-based protein microarray, together with the carbonylation
      pattern of the individual fibrinogen chains, possible changes in the molecular
      secondary and tertiary structure and reactivity with the insulin-like growth
      factor-binding protein 1 (IGFBP-1) in patients with cirrhosis. The results
      pointed to an increase in several carbohydrate moieties: tri/tetra-antennary
      structures, Gal beta-1,4 GlcNAc, terminal alpha-2,3 Sia and alpha-1,3 Man, and a
      decrease in core alpha-1,6 Fuc and bi-antennary galactosylated N-glycans with
      bisecting GlcNAc. Fibrinogen Aalpha chain was the most susceptible to
      carbonylation, followed by the Bbeta chain. Cirrhosis induced additional protein
      carbonylation, mostly on the alpha chain. Spectrofluorimetry and CD spectrometry
      detected reduction in the alpha-helix content, protein unfolding and/or
      appearance of modified amino acid residues in cirrhosis. The amount of complexes
      which fibrinogen forms with IGFBP-1, another factor involved in wound healing was
      significantly greater in patients with cirrhosis than in healthy individuals. A
      more detailed knowledge of individual molecules in coagulation process may
      contribute to deeper understanding of coagulopathies and the results of this
      study offer additional information on the possible mechanisms involved in
      impaired coagulation due to cirrhosis.

PMID- 29655003
TI  - Evaluation of endogenous thrombin potential among patients with antithrombin
      deficiency.

PMID- 29655004
TI  - Midwifery students in health visitor placements: the importance of student-mentor
      relationships.
AB  - OBJECTIVE: The aim of this study was to explore midwifery students and health
      visitor practice mentors experiences of a health visiting placement for midwifery
      students, focusing on the student-mentor relationship. DESIGN: Interview study
      SETTING: East London, United Kingdom PARTICIPANTS: Eighteen students and eighteen
      mentors were invited to take part in an interview. Ten midwifery students (55.5%)
      and fifteen health visitor practice mentors (83.3%) took part in interviews or
      provided information via email. Thematic analysis was used to analyse findings.
      FINDINGS: The main study finding was that students reported valuing practice
      mentors who took the time to get to know them, were welcoming and enthusiastic
      and planned their time in advance. The mentors in turn spoke highly of the
      students who were keen and enthusiastic about the placement, but noted that not
      all students had appeared interested. KEY CONCLUSIONS: The findings from this
      small interview study show that taking time to make the students feel welcome was
      important to facilitate a student-mentor relationship. Another important factor
      in whether a student enjoyed their placement was the mentors' advance planning.

PMID- 29655005
TI  - Psychological adaptation after peripartum cardiomyopathy: A qualitative study.
AB  - BACKGROUND: Peripartum cardiomyopathy (PPCM) is a rare and potentially life
      threatening condition of heart failure affecting women with no previous heart
      disease in the last months of pregnancy and up to six months after childbirth.
      OBJECTIVE: To explore women's experiences of the process of regaining
      psychological balance and wellbeing (i.e. psychological adaptation) after having
      experienced severe peripartum morbidity. DESIGN: A qualitative exploratory
      research design was applied to guide the study. Data was collected through in
      depth, semi-structured, face-toface telephone and e-mail interviews. Thematic
      analysis was applied in the data analysis. SETTING: The study was a sub-study of
      a larger nationwide research study investigating the incidence and clinical
      outcome of peripartum cardiomyopathy in Denmark during a ten-year period of 2005
      2014. PARTICIPANTS: Through a criterion-based sampling strategy, 14 Danish women
      with peripartum cardiomyopathy were recruited for participation in the study. In
      relation to severity of disease, demographics and pregnancy related
      characteristic, the sample showed a wide range of diversity. FINDINGS: The
      overarching theme of the thematic analysis was identified to be Recovering to a
      new normal after peripartum cardiomyopathy. The overarching theme was comprised
      by five main themes: Losing trust, Silence after chaos, Disrupted early
      mothering, Choices made for me and not by me, and Ability to mobilize inner
      resources. CONCLUSIONS: Findings from this study suggest that women are
      vulnerable in the time after PPCM diagnosis and struggle to find psychological
      balance in their life. The need for professional psychological support was often
      unmet and the physical symptoms were foregrounded in the recovery period. After
      PPCM, follow-up on psychological wellbeing and morbidity should be offered to
      women routinely.

PMID- 29655006
TI  - Turkish adaptation of the pregnancy-related anxiety questionnaire-revised 2:
      Validity and reliability study in multiparous and primiparous pregnancy.
AB  - OBJECTIVE: The purpose of this study was to create a Turkish version of the
      Pregnancy-Related Anxiety Questionnaire-Revised 2 (PRAQR2), which was revised for
      application to multiparous and primiparous pregnancy, and to explore its
      psychometric characteristics in multiparous and primiparous pregnancy. DESIGN:
      This study was methodologically designed to assess the reliability and validity
      of the PRAQ-R2. SETTING: The study was carried out in the obstetrics clinic of a
      training and research hospital in Malatya. PARTICIPANTS: A total of 616 healthy
      pregnant women (399 multiparous and 217 primiparous) constituted the sample of
      the study. METHODS: The cultural adaptation process of the questionnaire was
      conducted in three phases: language validity, content validity, and pilot
      application. Exploratory factor analysis (EFA) and confirmatory factor analysis
      (CFA) were used to test the construct validity of the questionnaire. The
      reliability of the PRAQ-R2 was evaluated with Cronbach's alpha internal
      consistency coefficient, item-total correlation, test-retest analysis, and
      parallel forms reliability. FINDINGS: The EFA revealed that the PRAQ-R2 consists
      of 10 items for the multiparous group and 11 for the primiparous group after
      adding the item ''I am anxious about the delivery because I have never
      experienced one before.'' The CFA for both groups supported the three-factor
      questionnaire yielded by the EFA. Good fit index values were obtained in both
      groups. Cronbach's alpha internal consistency coefficient ranged from 0.81 to
      0.93 for the multiparous group and 0.87 to 0.94 for the primiparous group for the
      complete PRAQ-R2 and each of its subdimensions. In addition, the item-total
      correlation, test-retest analysis, and parallel forms reliability of the
      questionnaire were highly correlated. CONCLUSION: The PRAQ-R2 is a valid and
      reliable instrument that can be used to evaluate the level of anxiety in Turkish
      pregnant women irrespective of parity. IMPLICATIONS FOR PRACTICE: The use of the
      PRAQ-R2 in prenatal healthcare services will contribute to the early diagnosis,
      treatment, and management of pregnancy-related anxiety.

PMID- 29655007
TI  - Antenatal diet and postpartum depressive symptoms: A prospective study.
AB  - Postnatal depression is a critical public health concern, and gaining a better
      understanding of possible causes is paramount. Recently, diet quality during
      pregnancy has emerged as a possible preventative measure in ameliorating
      postnatal depression, however the evidence-base exploring this association is
      immature. The aim of this study was to examine the association between
      consumption of food groups characteristic of a quality diet during pregnancy
      (that is fruit, vegetable and fish intake) and postnatal depressive symptoms at
      12 months postpartum. Pregnant women were recruited at 10-18 weeks gestation via
      advertising on online pregnancy forums, pregnancy and parenting magazines, and
      two Australian maternity clinics. Participants (n = 253) completed self-report
      questionnaires assessing fruit, vegetable and fish intake as well as depressive
      symptoms at early- to mid- pregnancy. Path analyses were conducted to examine
      whether fruit, vegetable and fish intake during pregnancy were associated with
      depressive symptom scores at 12 months postpartum. There were no associations
      between fruit, vegetable or fish intake in pregnancy and postnatal depressive
      symptoms. Antenatal diet quality as measured by intake of food groups associated
      with a healthy diet was not associated with postpartum depressive symptoms at 12
      months postpartum. Future research should consider the exploration of dietary
      quality as a measure of overall adherence to evidence-based dietary guidelines.

PMID- 29655008
TI  - Continuous professional development of Liberia's midwifery workforce-A
      coordinated multi-stakeholder approach.
AB  - BACKGROUND: Maternal and newborn mortality remains high in Liberia. There is a
      severe rural-urban gap in accessibility to health care services. A competent
      midwifery workforce is able to meet the needs of mothers and newborns. Evidence
      shows that competence can be assured through initial education along with
      continuous professional development (CPD). In the past, CPD was not regulated and
      coordinated in Liberia which is cpommon in the African region. AIM: To Support a
      competent regulated midwifery workforce through continuous professional
      development. METHODOLOGY: A new CPD model was developed by the Liberian Board for
      Nursing and Midwifery. With its establishment, all midwives and nurses are
      required to undertake CPD programmes consisting of certified training and
      mentoring in order to renew their practicing license. The new model is being
      piloted in one county in which regular mentoring visits that include skills
      training are being conducted combined with the use of mobile learning
      applications addressing maternity health issues. Quality control of the CPD pilot
      is assured by the Liberian Board for Nursing and Midwifery. The mentoring visits
      are conducted on a clinical level but are coordinated on the national and county
      level. SUCCESSES AND SUSTAINABILITY: CPD using mobile learning on smartphones and
      regular mentoring visits not only improved knowledge and skills of midwives and
      nurses but also provided a solution to enhance accessibility in rural areas
      through improved communication and transportation, as well as improved career
      development of health personnel working in remote areas. Mentors were trained on
      a national, county, and health facility level in the pilot county with mentoring
      visits conducted regularly. CONCLUSION: The CPD programme of the Liberian Board
      for Nursing and Midwifery, currently in pilot-testing by various partners, aims
      to highlight the positive impact of the coordinating role of both the regulatory
      body and health authorities. Using regular process and programme reviews to
      improve capacity, knowledge, and skills of health professionals.

PMID- 29655009
TI  - Selection procedure of bioprotective cultures for their combined use with High
      Pressure Processing to control spore-forming bacteria in cooked ham.
AB  - High Pressure Processing (HPP) and biopreservation can contribute to food safety
      by inactivation of bacterial contaminants. However these treatments are
      inefficient against bacterial endospores. Moreover, HPP can induce spore
      germination. The objective of this study was to select lactic acid bacteria
      strains to be used as bioprotective cultures, to control vegetative cells of
      spore-forming bacteria in ham after application of HPP. A collection of 63
      strains of various origins was screened for their antagonistic activity against
      spore-forming Bacillus and Clostridium species and their ability to resist to
      HPP. Some safety requirements should also be considered prior to their
      introduction into the food chain. Hence, the selection steps included the
      assessment of biogenic amine production and antibiotic resistance. No strain
      produced histamine above the threshold detection level of 50 ppm. From the
      assessment of antibiotic resistance against nine antibiotics, 14 susceptible
      strains were kept. Antagonistic action of the 14 strains was then assessed by the
      well diffusion method against pathogenic or spoilage spore-forming species as
      Bacillus cereus, Clostridium sp. like botulinum, Clostridium frigidicarnis, and
      Clostridium algidicarnis. One Lactobacillus curvatus strain and one Lactococcus
      lactis strain were ultimately selected for their widest inhibitory spectrum and
      their potential production of bacteriocin. A Lactobacillus plantarum strain was
      included as control. Their resistance to HPP and ability to regrow during chilled
      storage was then assessed in model ham liquid medium. Treatments of pressure
      intensities of 400, 500, and 600 MPa, and durations of 1, 3, 6, and 10 min were
      applied. After treatment, cultures were incubated at 8  degrees C during 30 days.
      Inactivation curves were then fitted by using a reparameterized Weibull model
      whereas growth curves were modelled with a logistic model. Although the two
      Lactobacillus strains were more resistant than L. lactis to HPP, the latter was
      the only strain able to regrow following HPP. The absence of biogenic amine
      production of this strain after growth on diced cube cooked ham was also shown.
      In conclusion this L. lactis strain could be selected as representing the best
      candidate for a promising preservative treatment combining biopreservation and
      HPP to control spore-forming bacteria in cooked ham.

PMID- 29655010
TI  - The mycobiota of the production environments of traditional Norwegian salted and
      dried mutton (pinnekjott).
AB  - In 2013, mould growth on Norwegian ready-to-sell pinnekjott (dried and cured lamb
      ribs) lead to the withdrawal of 200 tons of the product. The aim of this study
      was to identify the mycobiota at two Norwegian production sites and determine
      which species present the highest risk for reduced product quality and safety. A
      total of 485 samples from 2014, 2015 and 2016 were analysed for Penicillium and
      Aspergillus species. Both production sites showed a persistent mycobiota that
      remained stable over three seasons. Samples from site A were dominated by P.
      solitum while samples from site B were equally dominated by P. solitum, P.
      brevicompactum/bialowiezense and P. nordicum. The presence of P. nordicum was
      concentrated in one area of the production site where long-time stored hams were
      produced, but P. nordicum was also found sporadically in other parts of the site.
      Product samples taken from products with visible mould growth were at both sites
      dominated by P. solitum, highlighting its importance for product quality. P.
      nordicum was found frequently in the long-time stored hams, indicating a food
      safety risk of these products. However, P. nordicum was rarely isolated from
      pinnekjott. Aspergillus spp. were isolated from both sites at all samplings;
      however, there were no Aspergillus isolated from products, and no sites were
      repeatedly tested positive for identical species, indicating that Aspergillus is
      not a part of the persistent mycobiota, but enters the site sporadically. In
      conclusion, the study showed that a stable mycobiota consisting of few
      Penicillium species dominated the products and production environments of
      pinnekjott.

PMID- 29655011
TI  - Endocrine outcomes of endoscopic versus transcranial resection of
      craniopharyngiomas: A system review and meta-analysis.
AB  - It is unclear whether the endoscopic technique has any advantages over
      transcranial approach in the aspect of endocrine outcomes in patients with
      craniopharyngiomas, thus, we conducted a systematic review and meta-analysis. We
      conducted a comprehensive search of PubMed to identify relevant studies.
      Pituitary, hypothalamus functions and recurrence were used as outcome measures. A
      total of 39 cohort studies involving 3079 adult patients were included in the
      comparison. Among these studies, 752 patients across 17 studies underwent
      endoscopic transsphenoidal resection, and 2327 patients across 23 studies
      underwent transcranial resection. More patients in the endoscopic group (75.7%)
      had visual symptoms and endocrine symptoms (60.2%) than did patients in the
      transcranial group (67.0%, p = 0.038 and 42.0%, p = 0.016). There was no
      significant difference in hypopituitarism and pan-hypopituitarism after surgery
      between the two groups: 72.2% and 43.7% of the patients in endoscopic group
      compared to 80.7% and 48.3% in the transcranial group (p = 0.140 and p = 0.713).
      We observed same proportions of transient and permanent diabetes insipidus in
      both groups. Similar recurrence was observed in both groups (p = 0.131). Pooled
      analysis showed that neither weight gain (p = 0.406) nor memory impairment (p =
      0.995) differed between the two groups. Meta-regression analysis revealed that
      gross total resection contributed to the heterogeneity of recurrence proportion
      (p < 0.001). We observed similar proportions of endocrine outcomes and recurrence
      in both endoscopic and transcranial groups. More recurrences were observed in
      studies with lower proportions of gross total resection.

PMID- 29655012
TI  - Is rivaroxaban associated with higher morbidity and mortality in patients with
      traumatic head injuries? A retrospective cohort study comparing rivaroxaban, no
      anticoagulation, and phenprocoumon.
AB  - OBJECTIVES: The use of new anticoagulants potentially carries the risk of
      increased intracranial bleeding, but there is a lack of evidence. The aim of this
      study was to investigate whether the morbidity and mortality differs in head
      trauma patients depending on the type of anticoagulation. PATIENTS AND METHODS: A
      retrospective cohort study was conducted in 2009-2014. Based on sex, age, and
      Glasgow-Coma Scale (GCS), patients that received rivaroxaban were matched to two
      control groups, one that received no anticoagulant and another one that received
      phenprocoumon. The primary outcome was mortality. Among others, secondary outcome
      variables were the length of stay (LOS) at the hospital and presence of an
      intracranial injury. RESULTS: Sixty-nine patients (23 patients per group) were
      analyzed. The characteristics of patients did not differ significantly across
      groups. There were no significant differences between groups for the primary and
      secondary outcomes. Two patients died in the rivaroxaban group (one of them
      likely due to head trauma), while one patient died in the phenprocoumon group
      (likely not due to head trauma), and no patient died in the no anticoagulatoin
      group (p = 0.36). The LOS at the hospital was similar (5.0, 4.0, and 5.0 days; p
      = 0.94). An intracranial injury was observed in a similar number of patients in
      all groups (n = 11, n = 10, and n = 8; p = 0.75). CONCLUSION: Although limited in
      size, this study did not observe significant outcome differences in patients with
      traumatic head injuries, who received rivaroxaban, no anticoagulant or
      phenprocoumon. Although not significant, the only death likely due to head trauma
      in the study occurred in the rivaroxaban group. Larger studies are needed before
      clinical application of these findings.

PMID- 29655013
TI  - Comparison of operative outcomes of eloquent glioma resection performed under
      awake versus general anesthesia: A systematic review and meta-analysis.
AB  - Surgical resection of eloquent glioma can be achieved under general anesthesia
      (GA) or awake anesthesia (AA). The appeal of AA is that it facilitates
      intraoperative identification and avoidance of eloquent areas, which has the
      potential to minimize functional compromise. The aim of this meta-analysis was to
      compare the operative outcomes of eloquent glioma resection performed under GA
      compared to AA to assist in optimizing the decision algorithm between the two
      approaches. Searches of seven electronic databases from inception to December
      2017 were conducted following Preferred Reporting Items for Systematic reviews
      and Meta-Analyses (PRISMA) guidelines. There were 1037 articles identified for
      screening. Data were extracted and analyzed using meta-analysis of proportions. A
      total of 9 comparative studies were included for analysis. Resection of glioma
      involving eloquent areas achieved under AA is mostly comparable in terms of
      operative and functional outcomes to that of GA. AA did demonstrate significantly
      lower incidence of postoperative nausea and vomiting (PONV, OR, 0.17; p < 0.001)
      and shorter length of stay (LOS, MD, -1.76 days; p = 0.02) when compared to GA.
      Future studies that are larger, prospective, randomized, and include long term
      quality of life metrics will assist in elucidating the true clinical benefit of
      AA in resecting glioma involving eloquent areas. This will assist in further
      developing management protocol of these glioma.

PMID- 29655015
TI  - Toxic effect of [Omim]BF4 and [Omim]Br on antioxidant stress and oxidative damage
      in earthworms (Eisenia fetida).
AB  - In this paper, model soil organism, earthworms (Eisenia fetida), were selected to
      examine the chronic toxic effect of two different ionic liquids (ILs) [Omim]BF4
      and [Omim]Br. Earthworms were put into different ILs concentrations (0, 5, 10,
      20, 40 mg/kg) in artificial soil and random selected on days 7, 14, 21 and 28.
      Reactive oxygen species (ROS), antioxidant enzymes and detoxifying enzyme
      glutathione-S-transferase (GST) were researched for determination of antioxidant
      stress. Malondialdehyde (MDA) and olive tail moment (OTM) were researched to
      determine the oxidative damage. Both the pollutants had the same effect on
      earthworms: ILs led to accumulation of ROS, and then antioxidant enzymes and
      detoxification enzyme all changed to eliminate the effects of ROS, and the above
      process led to lipid peroxidation and DNA damage in earthworms. This paper shows
      that [Omim]BF4 and [Omim]Br both caused toxicity to earthworms and had the
      similar toxicity levels.

PMID- 29655014
TI  - InP/ZnS QDs exposure induces developmental toxicity in rare minnow (Gobiocypris
      rarus) embryos.
AB  - We investigated the in vivo toxicity of InP/ZnS quantum dots (QDs) in Chinese
      rare minnow (Gobiocypris rarus) embryos. The 72 h post-fertilization (hpf) LC50
      (median lethal concentration) was 1678.007 nmol/L. Rare minnows exposed to
      InP/ZnS QDs exhibited decreased spontaneous movement, decreased survival and
      hatchability rates, and an increased malformation rate. Pericardial edema, spinal
      curvature, bent tails and vitelline cysts were observed. Embryonic Wnt8a and Mstn
      mRNA levels were significantly up-regulated after InP/ZnS QDs treatment at 48 hpf
      (200 nmol/L) (p < 0.05). The superoxide dismutase (SOD) activity and
      malondialdehyde (MDA) levels at 96 hpf (800 nmol/L) had an increasing trend.
      Hsp70 mRNA expression was significantly changed at 48 hpf (200 nmol/L), but
      compared with the blank control, the different InP/ZnS QDs treatments did not
      significantly change the Olive tail moments (p > 0.05). Thus, InP/ZnS QDs caused
      teratogenic effects and death during the development of Chinese rare minnow
      embryos, but InP/ZnS QDs did not cause significant genetic toxicity during
      Chinese rare minnow development.

PMID- 29655016
TI  - Coil extensions improve line shapes by removing field distortions.
AB  - The static magnetic susceptibility of the rf coil can substantially distort the
      field B0 and be a dominant source of line broadening. A scaling argument shows
      that this may be a particular problem in microcoil NMR. We propose coil
      extensions to reduce the distortion. The actual rf coil is extended to a much
      longer overall length by abutted coil segments that do not carry rf current. The
      result is a long and nearly uniform sheath of copper wire, in terms of the static
      susceptibility. The line shape improvement is demonstrated at 43.9 MHz and in
      simulation calculations.

PMID- 29655017
TI  - The impact of 'missed care' on the professional socialisation of nursing
      students: A qualitative research study.
AB  - BACKGROUND: Missed care is a recently described concept that is subject to an
      increasing amount of international nursing research. The impact of missed care is
      associated with poorer patient outcomes (mortality and morbidity) and poorer
      levels of patient satisfaction with the services provided by the hospital. Missed
      care has also been linked to decreased staff satisfaction and increased intention
      to leave. Overall disaffection amongst registered nurses has also been reported.
      Professional socialisation refers to the acquisition of behaviours within
      cultural norms, and it has been suggested that students enter a period of
      professional socialisation during their programme. Whilst it has been proposed
      that students may absorb the characteristics of those around them, to date, no
      empirical studies have reported the impact of missed care on student nurses.
      METHODS: The aim of this project is to explore the impact of missed care on the
      professional socialisation of student nurses. A qualitative study was undertaken
      in one higher education institute in UK with final year pre-registration nursing
      degree (adult field) students. Focus group interviews, utilizing a broad topic
      guide, were used to collect data which was analysed using thematic analysis.
      FINDINGS: Student nurses were aware that some planned care is missed and these
      findings resonated with those identified in the literature. In addition to
      illuminating aspects of professional socialisation, analysis yielded five themes
      with regards to missed care: awareness, rationale, impact, strategies to avoid
      and influence of missed care on career aspiration. Student nurses exposed to
      missed care appear to accept this as part of their professional socialisation.
      CONCLUSION: With regards to professional socialisation, student nurses developed
      a pragmatic acceptance that care would be missed and that this could happen in
      any environment. As such they did not see missed care as influencing their career
      aspirations.

PMID- 29655018
TI  - Evaluation of an interprofessional education program for advanced practice
      nursing and dental students: The oral-systemic health connection.
AB  - BACKGROUND: In response to the growing body of evidence supporting the need for
      expanded interprofessional education among health professions, an
      interprofessional education program, based on the Interprofessional Education
      Collaborative Core Competencies, was piloted with nurse practitioner and dental
      students. OBJECTIVES: The purpose of this pilot study was to evaluate a
      technology enhanced interprofessional education program focused on the oral
      systemic health connection for nurse practitioner and dental students. DESIGN: A
      two-group comparative study using cross-sectional data and a quasi-experimental
      one-group pre-test/post-test design were used to evaluate students' knowledge of
      IPE core competencies, attitudes toward interprofessional education and
      interdisciplinary teamwork, and self-efficacy in functioning as a member of an
      interdisciplinary team. SETTING AND PARTICIPANTS: This program was implemented
      with master of science in nursing students pursuing a primary care nurse
      practitioner (NP) degree and dental students at a large urban academic health
      sciences center. Cohort 1 (N = 75) consisted of NP (n = 34) and dental students
      (n = 41) at the end of their degree program who participated in a one-time
      survey. Cohort 2 (N = 116) was comprised of second-year NP students (n = 22) and
      first-year dental students (n = 94) who participated in the IPE program. METHODS:
      Students participated in a multi-faceted educational program consisting of
      technology- enhanced delivery as well as interactive exercises in the joint
      health assessment course. Data were collected prior to the initiation and at the
      conclusion of the program. RESULTS: Nurse practitioner and dental students who
      participated in the program had better self-efficacy in functioning as a member
      of an interdisciplinary team than graduating students who did not participate.
      Students from both nursing and dentistry who participated in the program had
      significantly improved self-efficacy in functioning in interprofessional teams
      from pre- to post-test. CONCLUSION: An interprofessional education program can be
      a valuable addition to the health professions curriculum of nurse practitioner
      and dental students. Care must be taken to address logistical issues when working
      with students in different academic programs.

PMID- 29655019
TI  - Emotional intelligence among nursing students: Findings from a cross-sectional
      study.
AB  - BACKGROUND: Emotional intelligence in nursing is of global interest.
      International studies identify that emotional intelligence influences nurses'
      work and relationships with patients. It is associated with compassion and care.
      Nursing students scored higher on measures of emotional intelligence compared to
      students of other study programmes. The level of emotional intelligence increases
      with age and tends to be higher in women. OBJECTIVES: This study aims to measure
      the differences in emotional intelligence between nursing students with previous
      caring experience and those without; to examine the effects of gender on
      emotional intelligence scores; and to test whether nursing students score higher
      than engineering colleagues on emotional intelligence measures. DESIGN: A cross
      sectional descriptive study design was used. SETTINGS AND PARTICIPANTS: The study
      included 113 nursing and 104 engineering students at the beginning of their first
      year of study at a university in Slovenia. DATA: Emotional intelligence was
      measured using the Trait Emotional Intelligence Questionnaire (TEIQue) and
      Schutte Self Report Emotional Intelligence Test (SSEIT). METHODS: Shapiro-Wilk's
      test of normality was used to test the sample distribution, while the differences
      in mean values were tested using Student t-test of independent samples. RESULTS:
      Emotional intelligence was higher in nursing students (n = 113) than engineering
      students (n = 104) in both measures [TEIQue t = 3.972; p < 0.001; SSEIT t =
      8.288; p < 0.001]. Although nursing female students achieved higher emotional
      intelligence scores than male students on both measures, the difference was not
      statistically significant [TEIQue t = -0.839; p = 0.403; SSEIT t = -1.159; p =
      0.249]. EI scores in nursing students with previous caring experience were not
      higher compared to students without such experience for any measure [TEIQue t = 
      1.633; p = 0.105; SSEIT t = -0.595; p = 0.553]. CONCLUSIONS: Emotional
      intelligence was higher in nursing than engineering students, and slightly higher
      in women than men. It was not associated with previous caring experience.

PMID- 29655020
TI  - Anomalous course of the sigmoid colon and the mesosigmoid encountered during
      colectomy. A case report of a redundant loop of sigmoid colon.
AB  - : Introduction Sigmoid colon constitutes a part of the large intestine that
      presents several congenital anatomic variations. In particular, the presence of a
      redundant loop of sigmoid colon is of tremendous importance for surgeons,
      obstetricians and radiologists, since it is closely related to multiple
      pathological conditions and functional implications of the neighboring anatomical
      structures. PRESENTATION OF CASE: An unusual anatomic variation in position and
      length of the sigmoid colon and its mesocolon was unexpectedly detected during
      right hemicolectomy to a 67-year-old Caucasian male patient due to colon cancer.
      The operation was uneventful. A meticulous review of the literature was conducted
      as well. DISCUSSION: A redundant loop of sigmoid colon may go unnoticed or it
      might lead to urinary, digestive and vascular complications. Its presence is
      associated with acute and chronic pathological conditions, sigmoid volvulus and
      serious confusions in radiological diagnosis and instrumentation. CONCLUSION:
      Surgeons' thorough knowledge concerning this rare anatomic variation is
      fundamental and crucial in order to establish a correct diagnosis and assert the
      appropriate management when performing operations including pelvis and abdomen.

PMID- 29655021
TI  - Obesity induced T cell dysfunction and implications for cancer immunotherapy.
AB  - Obesity has been shown to increase risk for a number of different disorders,
      including cancer. In addition, obesity is also associated with immune
      dysfunction, which could contribute to its strong association with other
      comorbidities. Recently, the immune system has been found to be heavily regulated
      by changes in metabolism. In particular, T cells are able to respond to intrinsic
      metabolic regulatory mechanisms, as well as extrinsic factors such as the changes
      in metabolite availability. The dysfunctional metabolic environment created by
      obesity could therefore have a direct impact on T cell responses. In this review,
      we highlight recent findings in the fields of T cell biology and obesity, with a
      focus on mechanisms driving T cell dysfunction and potential implications for
      immunotherapeutic treatment of cancer.

PMID- 29655022
TI  - Mass cytometry: a powerful tool for dissecting the immune landscape.
AB  - Advancement in methodologies for single cell analysis has historically been a
      major driver of progress in immunology. Currently, high dimensional flow
      cytometry, mass cytometry and various forms of single cell sequencing-based
      analysis methods are being widely adopted to expose the staggering heterogeneity
      of immune cells in many contexts. Here, we focus on mass cytometry, a form of
      flow cytometry that allows for simultaneous interrogation of more than 40
      different marker molecules, including cytokines and transcription factors,
      without the need for spectral compensation. We argue that mass cytometry occupies
      an important niche within the landscape of single-cell analysis platforms that
      enables the efficient and in-depth study of diverse immune cell subsets with an
      ability to zoom-in on myeloid and lymphoid compartments in various tissues in
      health and disease. We further discuss the unique features of mass cytometry that
      are favorable for combining multiplex peptide-MHC multimer technology and
      phenotypic characterization of antigen specific T cells. By referring to recent
      studies revealing the complexities of tumor immune infiltrates, we highlight the
      particular importance of this technology for studying cancer in the context of
      cancer immunotherapy. Finally, we provide thoughts on current technical
      limitations and how we imagine these being overcome.

PMID- 29655023
TI  - Morphology and Molecular Phylogeny of Peritrich Ciliate Epibionts on Pelagic
      Diatoms: Vorticella oceanica and Pseudovorticella coscinodisci sp. nov.
      (Ciliophora, Peritrichia).
AB  - Consortia of the peritrich ciliate Vorticella oceanica and the planktonic diatom
      Chaetoceros coarctactus are reported from the South Atlantic Ocean. The
      morphologies of the constituent species were similar to their counterparts from
      other geographical regions, revealing a widespread distribution in tropical
      waters. Besides, we describe Pseudovorticella coscinodisci sp. nov. that lives on
      Coscinodiscus wailesii and other pelagic diatoms off Brazil. The zooids were 34
      45MUm long, and 19-30MUm wide with a stalk too short to coil. The cell surface
      showed a reticulate pellicle with 18-19 and 11-12 rows above and below the aboral
      ciliary wreath, respectively. In the SSU rDNA phylogeny V. oceanica clustered
      between the clades of Vorticella and Pseudovorticella/Epicarchesium, and
      Pseudovorticella coscinodisci sp. nov. clustered as a sister group of
      Pseudovorticella paracratera and P. sinensis. The V. oceanica-C. coarctactus
      consortium likely represents an obligate species-specific mutualistic symbiosis
      as the constituents are not known as free-living forms. In contrast, the diatom
      hosts are known as free-living forms in the consortia of Pseudovorticella
      coscinodisci. The new molecular data and species description will be valuable
      dataset for future research on the diversity and ecological significance of
      ciliate-diatom epibiotic consortia.

PMID- 29655025
TI  - Design, facile synthesis, and evaluation of novel spiro- and pyrazolo[1,5
      c]quinazolines as cholinesterase inhibitors: Molecular docking and MM/GBSA
      studies.
AB  - Given the wide spectrum of biological uses of pyrazolo[1,5-c]quinazoline and
      spiro-quinazoline derivatives as anticancer, anti-inflammatory analgesic agents,
      and their therapeutic applications in neurodegenerative disorders, it is
      compulsory to find easy, efficient, and simple methods to obtain and chemically
      diversify these families of compounds, thereby improving their biological
      applications. In this paper, we report the design and eco-friendly two-step
      synthesis of novel, fused spiro-pyrazolo[1,5-c]quinazoline derivatives as
      cholinesterase inhibitors. In addition, we studied their protein-ligand
      interactions via molecular docking and MM/GBSA calculations for a further
      rational design of more potent inhibitors. In first step, 2-(1H-pyrazol-5
      yl)anilines were obtained through microwave (MW) assisted solvent-free/catalyst
      free conditions and the second step involved the synthesis of the spiro
      pyrazolo[1,5-c]quinazolines by a cyclocondensation reaction between 2-(1H-pyrazol
      5-yl)anilines and cyclic ketones, or acetophenones, using stirring at room
      temperature. The compounds were obtained in high purity, good yields (50-97%),
      and at varying reaction times. The spiro-compounds were evaluated as
      acetylcholinesterase and butyrylcholinesterase inhibitors (AChEIs/BuChEIs)
      respectively, and the most potent compound exhibited a moderate AChE inhibitory
      activity (5f: IC50 = 84 MUM). Molecular docking studies indicated that the
      binding mode of the compound 5f share common characteristics with the
      galantamine/donepezil-AChE complexes. Moreover, free binding energy (DeltaG)
      calculations showed a good agreement with the experimental biological activity
      values. Our theoretical results indicated that halogen bond interactions could be
      involved with differential potency of these compounds and provide a new starting
      point to design novel pyrazolo[1,5-c]quinazolines as new anti-Alzheimer agents.

PMID- 29655026
TI  - Interoceptive influences on peripersonal space boundary.
AB  - Integration of body-related signals within the peripersonal space (PPS)
      contributes to bodily self-awareness. Whereas several studies have shown how
      individual PPS extension is shaped by external factors, e.g. during interactions
      with people and objects, no studies have looked at interoceptive influences on
      PPS extension. We exposed participants to an audio-tactile interaction task, to
      measure their PPS boundary (Session 1), and to a heartbeat counting task and a
      time estimation task, to specifically assess their interoceptive accuracy
      (Session 2). Participants' traits of private self-consciousness and social
      anxiety were also evaluated, to account for their possible effect on the relation
      between interoception and PPS representation. We found that higher interoceptive
      accuracy specifically predicts narrower PPS boundary. Moreover, this relation is
      moderated by individual traits of private self-consciousness, but not social
      anxiety. Extending the concept of interoceptive influences on exteroceptive body
      representations to PPS, our results, first, support the idea that a dynamic
      balance between intero-exteroceptive processing might represent a general
      principle underlying bodily self-awareness; second, they shed light on how
      interoception may affect also the way we interface with the external world.
      Finally, showing that, in order for interoceptive accuracy to be effective on the
      intero-exteroceptive balance, it is important that individuals tend to focus on
      inner sensations and feelings, our results suggest that a comprehensive intero
      exteroceptive model of bodily self-awareness should be (at least) a three
      dimensional model that includes individual self-consciousness traits.

PMID- 29655027
TI  - Identification of nonsynonymous TP53 mutations in hydatidiform moles.
AB  - Hydatidiform mole (HM), an unusual pregnancy with pure or predominant paternal
      genetic contribution, is the most common form of gestational trophoblastic
      disease. Most HM regress after uterine evacuation but some will develop into
      persistent disease or even frank malignancy. Although p53 is highly expressed in
      HM, TP53 mutations have rarely been detected in previous studies. Here we
      screened for specific missense mutations on several TP53 hotspots in 49 HMs using
      a highly sensitive pyrosequencing approach and revealed the significant existence
      of such mutations in HM tissues. A particularly high frequency (~59% of the
      cases) of p53 inactivating mutation on exon 7 has been detected. Our
      identification of hitherto unreported TP53 mutations in HM suggests the presence
      of p53 mutants and reflects the advantages of using pyrosequencing for point
      mutation detection in clinical samples. Traditional sequencing method may have
      overlooked such mutations that only occur in a small population of trophoblasts.

PMID- 29655024
TI  - Frontotemporal stimulation modulates semantically-guided visual search during
      confrontation naming: A combined tDCS and eye tracking investigation.
AB  - Transcranial direct current stimulation (tDCS) was paired with eye tracking to
      elucidate contributions of frontal, temporoparietal and anterior temporal cortex
      to early visual search patterns during picture naming (e.g., rapid visual
      scanning to diagnostic semantic features). Neurotypical adults named line
      drawings of objects prior to and following tDCS in three separate sessions, each
      employing a unique electrode montage. The gaze data revealed montage by
      stimulation (pre/post) interaction effects characterized by longer initial visual
      fixations (mean difference = 89 ms; Cohen's d = .8) and cumulative fixation
      durations (mean difference = 98 ms; Cohen's d = .9) on key semantic features
      (e.g., the head of an animal) after cathodal frontotemporal stimulation relative
      to the pre-stimulation baseline. We interpret these findings as reflecting a tDCS
      induced modulation of semantic contributions of the anterior temporal lobe(s) to
      top-down influences on object recognition. Further, we discuss implications for
      the optimization of tDCS for the treatment of anomia in aphasia.

PMID- 29655028
TI  - Modulation of human osteoclastogenesis and osteoblastogenesis by lycopene.
AB  - Lycopene is a lipid-soluble pigment that is mainly found in tomato. It is the
      carotenoid that presents the highest antioxidant potential, and due to that, it
      has been implicated in a decrease of the risk of several oxidative-stress-related
      disorders, such as cancer, inflammatory diseases and osteoporosis. Nevertheless,
      at the present, there is no detailed information about how lycopene affects bone
      metabolism. The aim of the present work was to characterize the cellular and
      molecular effects of lycopene on human osteoclast and osteoblast differentiation
      and function. It was observed that lycopene, at levels found in plasma after the
      ingestion of lycopene-containing products, decreased osteoclast differentiation
      but did not affect cell density/survival; calcium-phosphate resorbing ability was
      also decreased. On the other hand, osteoblast proliferation (via a decrease on
      apoptosis) and differentiation were increased in the presence of lycopene. The
      observed effects in both cell types appeared to be related to significant changes
      in MEK signaling pathway, but also in protein kinase C pathway in osteoclasts and
      NFkB signaling in osteoblasts. In conclusion, lycopene appears to promote an
      anabolic state of bone metabolism, stimulating osteoblastogenesis and inhibiting
      osteoclastogenesis, which may contribute to the promotion of a proper health
      status of bone tissue. This information might be relevant for the prevention and
      delay in the progression of osteolytic bone conditions.

PMID- 29655029
TI  - Trainee physician turnover and 30-day mortality in Korean intensive care units.
AB  - PURPOSE: Previous studies have found an increase in in-hospital mortality when
      trainee physicians rotate. Our retrospective cohort study investigated whether
      trainee physicians' turnover influenced 30-day mortality in Korean intensive care
      units (ICUs), which have high-intensity daytime intensivist coverage only on
      weekdays. MATERIALS AND METHODS: Participants were adults over 19years old
      admitted to ICUs in a Korean tertiary care academic hospital between 2012 and
      2016. Demographic and clinical data were collected on admission, and dates of
      death recorded. The primary outcome was the association between ICU admission in
      the turnover periods (March and May) and 30-day mortality after admission to ICUs
      with high-intensity daytime intensivist coverage. RESULTS: Overall, there was no
      significant correlation between ICU admission during turnover periods and 30-day
      mortality [hazard ratio (HR), 1.06; 95% confidence interval (CI), 0.83-1.35,
      P=0.647]; the same trend was found for ICU admissions when there was no
      intensivist coverage (HR: 1.24, 95% CI: 0.91-1.69, P=0.177). CONCLUSIONS: We
      found no overall association between physician turnover and 30-day mortality of
      patients admitted to ICUs with high-intensity daytime intensivist coverage or
      with no intensivist coverage.

PMID- 29655030
TI  - Associations between pain intensity and urge to smoke: Testing the role of
      negative affect and pain catastrophizing.
AB  - BACKGROUND: Cigarette smokers are more likely to experience pain than nonsmokers,
      and experimental research indicates that pain is a potent motivator of smoking.
      Urge to smoke is a predictor of early relapse, yet associations between pain and
      urge to smoke have yet to be tested among daily smokers. This study aimed to
      conduct the first crosssectional test of associations between current pain
      intensity and urge to smoke, and to test the role of negative affect and pain
      catastrophizing in relations between pain intensity and urge to smoke. METHODS:
      Participants (N = 229, 42.4% Female, 38.9% black/African American, Mcpd = 21.9)
      were recruited for a laboratory study of pain and smoking, and these data were
      collected at the baseline session. Data were analyzed using a series of
      regressions and conditional process models. RESULTS: Current pain intensity was
      positively associated with urge to smoke, and urge to smoke for the relief of
      negative affect. There was an indirect association via state negative affect,
      such that pain intensity was positively associated with negative affect, which in
      turn was associated with greater urge to smoke. Further, positive associations
      between pain intensity and urge to smoke were only evident among smokers who
      endorsed low (vs high) levels of catastrophizing. CONCLUSIONS: These findings
      contribute to an emerging literature indicating that pain and related constructs
      are relevant to the maintenance of tobacco smoking. Future research should
      examine how painrelevant cognitive-affective factors may influence associations
      between the experience of pain and motivation to smoke tobacco.

PMID- 29655032
TI  - Increasing rates of quetiapine overdose, misuse, and mortality in Victoria,
      Australia.
AB  - BACKGROUND: Quetiapine is misused due to its anxiolytic and hedonic effects and
      has been associated with deliberate self-harm. This study analyzed quetiapine
      related calls to the Victorian Poisons Information Centre (VPIC), coronial data
      from Victorian Institute of Forensic Medicine (VIFM) and prescribed data from the
      Pharmaceutical Benefits Scheme (PBS) to determine current trends in overdose,
      misuse and mortality. METHODS: This was a retrospective review of multiple
      databases. Calls to VPIC and coronial data from the VIFM were reviewed from 2006
      to 2016. PBS prescription data from 2000 to 2015 was obtained from the Australian
      Statistics on Medicines website. RESULTS: VPIC data indicated a 6-fold increase
      in the number of quetiapine-related calls over the 11-year period of which most
      were overdose-related (77%). Overdose and misuse calls increased by 6-fold and
      6.6-fold, respectively. Coronial data also indicated a rise in quetiapine-related
      harm; a 7.4-fold increase in quetiapine-related deaths was recorded for the same
      period. Similarly, Australian PBS data showed that quetiapine prescriptions
      increased 285-fold since 2000. There was a significant positive correlation
      between the increase in prescribing and overdose (r = 0.75, p < 0.001), and
      prescribing and mortality (r = 0.82, p < 0.01). CONCLUSIONS: This study revealed
      an increasing trend of misuse, non-fatal and fatal overdoses in Victoria over the
      last decade. The increasing rates of prescriptions in Australia and thus
      increased quetiapine availability are likely to have contributed to increased
      poisoning and mortality. Further research is warranted to explore the reasons
      behind increased prescribing, including off-label use.

PMID- 29655033
TI  - CRISPR/Cas approach: A new way of looking at plant-abiotic interactions.
AB  - It is not the most grounded of the species that survive, nor the most shrewd,
      however one most receptive to change. Crop plants being sessile are subjected to
      various abiotic stresses resulting significant yield losses about an average of
      more than 50 percent, thus greatly threatening the global crop production. In
      this regard, plant breeding innovations and genetic engineering approaches have
      been used in the past for generating stress tolerant crop genotypes, but due to
      complex inheritance of abiotic stress tolerance these approaches are not enough
      to bring significant trait improvement and to guarantee world's future sustenance
      security. Although, RNA interference (RNAi) technology has been utilized amid the
      most recent decades to produce plants tolerant to environmental stress. But this
      technique ordinarily prompts to down-regulate as opposed to complete inhibition
      of target genes. Therefore, scientist/researchers were looking for techniques
      that should be efficient, precise and reliable as well as have potential to solve
      the issues experienced by previous approaches, and hence the CRISPR/Cas system
      came into spotlight. Although, only few studies using CRISPR/Cas approach for
      targeting abiotic stress tolerance related genes have been reported, but
      suggested its effective role for future applications in molecular breeding to
      improve abiotic stress tolerance. Hence, genome engineering via CRISPR-Cas system
      for targeted mutagenesis promise its immense potential in generating elite
      cultivars of crop plants with enhanced and durable climate resilience. Lastly,
      CRISPR-Cas will be future of crop breeding as well as to target minor gene
      variation of complex quantitative traits, and thus will be the key approach to
      release global hunger and maintain food security.

PMID- 29655031
TI  - Differences in nicotine dependence, smoke exposure and consumer characteristics
      between smokers of machine-injected roll-your-own cigarettes and factory-made
      cigarettes.
AB  - BACKGROUND: Consumption of machine-injected roll-your-own (RYO) filtered
      cigarettes made from pipe tobacco increased almost 7-fold from 2008 to 2011 in
      the United States. METHODS: We used data from the Pennsylvania Adult Smoking
      Study to compare the differences in sociodemographic, smoking topography,
      nicotine dependence, and cotinine levels between 280 smokers using factory made
      (FM) cigarettes and 68 smokers using RYO cigarettes. RESULTS: RYO smokers were
      older (41 vs. 37, P = 0.053), had significantly lower levels of income (P <
      0.001) and education (P = 0.007), and were less likely to be fully employed (P =
      0.009). RYO smokers consumed more cigarettes per day [CPD] (21 vs. 15, P <
      0.001), and had a higher mean score on the Fagerstrom Test for Cigarette/Nicotine
      Dependence (5.2 vs. 4.1, P < 0.001). The main reasons for choosing RYO cigarettes
      were the lower cost (68%) and believed they are less harmful (12%). The average
      cost per pack of FM cigarettes was $5.74 vs. $1.13 for RYO. In multiple
      regression analyses, RYO smokers had significantly lower cotinine levels across
      all levels of CPD. Among smokers of king-size cigarettes, mean interpuff interval
      (P < 0.05) and total smoke duration (P < 0.01) per cigarette was significantly
      greater in RYO smokers. In laboratory measurements, RYO cigarettes contained more
      tobacco by weight than FM cigarettes, but weight varied by both tobacco and
      cigarette tube brands. CONCLUSIONS: Machine-injected RYO cigarettes made from
      pipe tobacco are cheaper than FM cigarettes but may have higher abuse liability.
      Smokers who might otherwise reduce their cigarette consumption or quit altogether
      may continue to smoke RYO cigarettes due to their affordability.

PMID- 29655034
TI  - Strangulation of the heart presenting as sudden cardiac death: A deadly but
      forgotten complication of epicardial pacing device.
AB  - Strangulation of the heart appears to be an exceedingly rare mechanical
      phenomenon that can develop with epicardial pacing wires in individuals
      undergoing somatic growth. Over the passage of time, owing to size mismatch
      between a fixed wire length and dynamically growing heart, the epicardial wire
      may embed around the heart resulting in the progressive over-pressurizing of
      involved cardiac structures. Depending on the location of the peak constriction
      pressures, cardiac strangulation may damagingly affect coronary circulation,
      heart valves function, or physiologic filling of the heart chambers, with risk of
      myocardial ischemia, decreased cardiac output, acute cardiac failure, ventricular
      arrhythmias and death. We report a case of a 29-year-old male with sudden cardiac
      death owing to cardiac strangulation with epicardial pacing wire that had been
      retained in place almost 30 years. At autopsy, an enlarged and abnormally
      contoured heart was found to be strangulated by an epicardial pacing wire;
      histopathologic examination confirmed hypertrophy of the myocardial fibers,
      myofiber disarrangement, and replacement-type fibrolipomatosis. In addition, this
      article consolidates the available literature on cardiac strangulation by an
      epicardial wire and highlight relevant clinical and medico-legal features for the
      forensic professionals.

PMID- 29655035
TI  - An insoluble iron complex coated cathode enhances direct electron uptake by
      Rhodopseudomonas palustris TIE-1.
AB  - Microbial electrosynthesis (MES) is a promising bioelectrochemical approach to
      produce biochemicals. A previous study showed that Rhodopseudomonas palustris TIE
      1 can directly use poised electrodes as electron donors for photoautotrophic
      growth at cathodic potentials that avoid electrolytic H2 production
      (photoelectroautotrophy). To make TIE-1 an effective biocatalyst for MES, we need
      to improve its electron uptake ability and growth under photoelectroautotrophic
      conditions. Because TIE-1 interacts with various forms of iron while using it as
      a source of electrons for photoautotrophy (photoferroautotrophy), we tested the
      ability of iron-based redox mediators to enhance direct electron uptake. Our data
      show that soluble iron cannot act as a redox mediator for electron uptake by TIE
      1 from a cathode poised at +100mV vs. Standard Hydrogen electrode. We then tested
      whether an immobilized iron-based redox mediator Prussian blue (PB) can enhance
      electron uptake by TIE-1. Chronoamperometry indicates that cathodic current
      uptake by TIE-1 increased from 1.47+/-0.04 to 5.6+/-0.09MUA/cm2 (3.8 times).
      Overall, our data show that immobilized PB can enhance direct electron uptake by
      TIE-1.

PMID- 29655036
TI  - Hair cortisol and progesterone detection in dairy cattle: interrelation with
      physiological status and milk production.
AB  - Hair cortisol concentrations (HCCs) and hair progesterone concentrations (HPCs)
      allow monitoring long-term retrospective steroid levels. However, there are still
      gaps in the knowledge of the mechanisms of steroid deposition in hair and its
      potential application in dairy cattle research. This study aimed to evaluate the
      potential uses of hair steroid determinations by studying the interrelations
      between HCC, HPC, physiological data from cows, and their milk production and
      quality. Cortisol and progesterone concentrations were analyzed in hair from 101
      milking Holstein Friesian cows in a commercial farm. Physiological data were
      obtained from the 60 d prior to hair collection. Moreover, productive data from
      the month when hair was collected and the previous one were also obtained as well
      as at 124 d after hair sampling. Significant but weak correlations were found
      between HCC and HPC (r = 0.25, P < 0.0001) and between HPC and age (r = 0.06, P =
      0.0133). High HCC were associated with low milk yields from the 2 previous months
      to hair sampling (P = 0.0396) and during the whole lactation (P < 0.0001). High
      HCC were also related to high somatic cell count (P = 0.0241). No effect of HCC
      on fat or protein content was detected. No significant correlations were detected
      between hair steroid concentrations and pregnancy status, days of gestation,
      parturition category (primiparous vs multiparous), number of lactations or days
      in milk. The relationship between physiological variables and HCC or HPC could
      depend on the duration of the time period over which hair accumulates hormones.
      Steroid concentrations in hair present high variability between individuals but
      are a potential tool for dairy cattle welfare and production research by
      providing a useful and practical tool for long-term steroid monitoring.

PMID- 29655037
TI  - Genetic polymorphisms of GRIN2A and GRIN2B modify the neurobehavioral effects of
      low-level lead exposure in children.
AB  - Lead (Pb) is neurotoxic and children are highly susceptible to this effect,
      particularly within the context of continuous low-level Pb exposure. A current
      major challenge is identification of children who may be uniquely susceptible to
      Pb toxicity because of genetic predisposition. Learning and memory are among the
      neurobehavioral processes that are most notably affected by Pb exposure, and
      modification of N-methyl-D-aspartate receptors (NMDAR) that regulate these
      processes during development are postulated to underlie these adverse effects of
      Pb. We examined the hypothesis that polymorphic variants of genes encoding
      glutamate receptor, ionotropic, NMDAR subunits 2A and 2B, GRIN2A and GRIN2B,
      exacerbate the adverse effects of Pb exposure on these processes in children.
      Participants were subjects who participated as children in the Casa Pia Dental
      Amalgam Clinical Trial and for whom baseline blood Pb concentrations and annual
      neurobehavioral test results over the 7 year course of the clinical trial were
      available. Genotyping assays were performed for variants of GRIN2A (rs727605 and
      rs1070503) and GRIN2B (rs7301328 and rs1806201) on biological samples acquired
      from 330 of the original 507 trial participants. Regression modeling strategies
      were employed to evaluate the association between genotype status, Pb exposure,
      and neurobehavioral test outcomes. Numerous significant adverse interaction
      effects between variants of both GRIN2A and GRIN2B, individually and in
      combination, and Pb exposure were observed particularly among boys,
      preferentially within the domains of Learning & Memory and Executive Function. In
      contrast, very few interaction effects were observed among similarly genotyped
      girls with comparable Pb exposure. These findings support observations of an
      essential role of GRIN2A and GRIN2B on developmental processes underlying
      learning and memory as well as other neurological functions in children and
      demonstrate, further, modification of Pb effects on these processes by specific
      variants of both GRIN2A and GRIN2B genes. These observations highlight the
      importance of genetic factors in defining susceptibility to Pb neurotoxicity and
      may have important public health implications for future strategies aimed at
      protecting children and adolescents from potential health risks associated with
      low-level Pb exposure.

PMID- 29655038
TI  - Electron Spin Resonance (ESR) for the study of Reactive Oxygen Species (ROS) on
      the isolated frog skin (Pelophylax bergeri): A non-invasive method for
      environmental monitoring.
AB  - BACKGROUND: Reactive oxygen species (ROS) in biological tissues of elected
      biosentinels represent an optimal biomarker for eco-monitoring of polluted areas.
      Electron spin resonance (ESR) is the most definitive method for detecting,
      quantifying and possibly identifying radicals in complex systems. OBJECTIVE: A
      non-invasive method for monitoring polluted areas by the quantitative
      determination of ROS in frog skin biopsy is presented. METHODS: We assessed by
      ESR spectroscopy the ROS level in adult male of Pelophylax bergeri, specie not a
      risk of extinction, collected from the polluted Sarno River (SA, Italy) basin.
      The spin-trap ESR method was validated by immunohistochemical analysis of the
      well-assessed pollution biomarkers cytochrome P450 aromatase 1A (CYP1A) and
      glutathione S-transferase (GST), and by determining the poly(ADPribose)
      polymerase (PARP) and GST enzymatic activity. RESULTS: ROS concentration in skin
      samples from frogs collected in the polluted area is significantly higher than
      that determined for the unpolluted reference area. Immunohistochemical analysis
      of CYP1A and GST supported the reliability of our approach, even in the absence
      of evident morphological and ultrastructural differences. PARP activity assay,
      connected to possible oxidative DNA damage, and the detoxification index by GST
      enzymatic assay give statistically significant evidence that higher levels of ROS
      are associated to alterations of the different biomarkers. CONCLUSIONS: ROS
      concentration, measured by ESR on isolated frog skin, through the presented non
      lethal method, is a reliable biomarker for toxicity screening and represents a
      useful basic datum for future modelling studies on environmental monitoring and
      biodiversity loss prevention.

PMID- 29655039
TI  - Engaging outreach workers in the development of a farmworker health research
      agenda.
AB  - Farmworker health outreach workers have not traditionally been involved in the
      prioritization and design of research studies. This report from the field shares
      the results of a survey administered to outreach workers providing health
      services to farmworkers in North Carolina. Priority areas of research and best
      practices for engaged research are presented from the perspective of the outreach
      worker community. The purposeful involvement of outreach workers can make
      farmworker health research more meaningful and solution-oriented.

PMID- 29655040
TI  - Parental stress and air pollution increase childhood asthma in China.
AB  - BACKGROUND: Although air pollution and social stress may independently increase
      childhood asthma, little is known on their synergistic effect on asthma,
      particularly in China with high levels of stress and air pollution. OBJECTIVES:
      To examine associations between exposure to a combination of parental stress and
      air pollution and asthma prevalence in children. METHODS: We conducted a cohort
      study of 2406 preschool children in Changsha (2011-2012). A questionnaire was
      used to collect children's lifetime prevalence of asthma and their parental
      stress. Parental socioeconomic and psychosocial stresses were respectively
      defined in terms of housing size and difficulty concentrating. Children's
      exposure to ambient air pollutants was estimated using concentrations measured at
      monitoring stations. Associations between exposure to parental stress and air
      pollution and childhood asthma were estimated by multiple logistic regression
      models using odds ratio (OR) and 95% confidence interval (CI). RESULTS: Life time
      prevalence of asthma in preschool children (6.7%) was significantly associated
      with parental socioeconomic and psychosocial stresses with OR (95% CI)
      respectively 1.48 (1.02-2.16) and 1.64 (1.00-2.71). Asthma was also associated
      with exposure to air pollutants, with adjusted OR (95% CI) during prenatal and
      postnatal periods respectively 1.43 (1.10-1.86) and 1.35 (1.02-1.79) for SO2 and
      1.61 (1.19-2.18) and 1.76 (1.19-2.61) for NO2. The association with air pollution
      was significant only in children exposed to high parental stress, the association
      with parental stress was significant only in children exposed to high air
      pollution, and the association was the strongest in children exposed to a
      combination of parental stress and air pollution. Sensitivity analysis showed
      that the synergistic effects of parental stress and air pollution on childhood
      asthma were stronger in boys. CONCLUSIONS: Parental stress and air pollution were
      synergistically associated with increased childhood asthma, indicating a common
      biological effect of parental stress and air pollution during both prenatal and
      postnatal periods.

PMID- 29655041
TI  - Learning for pitch and melody discrimination in congenital amusia.
AB  - Congenital amusia is currently thought to be a life-long neurogenetic disorder in
      music perception, impervious to training in pitch or melody discrimination. This
      study provides an explicit test of whether amusic deficits can be reduced with
      training. Twenty amusics and 20 matched controls participated in four sessions of
      psychophysical training involving either pure-tone (500 Hz) pitch discrimination
      or a control task of lateralization (interaural level differences for bandpass
      white noise). Pure-tone pitch discrimination at low, medium, and high frequencies
      (500, 2000, and 8000 Hz) was measured before and after training (pretest and
      posttest) to determine the specificity of learning. Melody discrimination was
      also assessed before and after training using the full Montreal Battery of
      Evaluation of Amusia, the most widely used standardized test to diagnose amusia.
      Amusics performed more poorly than controls in pitch but not localization
      discrimination, but both groups improved with practice on the trained stimuli.
      Learning was broad, occurring across all three frequencies and melody
      discrimination for all groups, including those who trained on the non-pitch
      control task. Following training, 11 of 20 amusics no longer met the global
      diagnostic criteria for amusia. A separate group of untrained controls (n = 20),
      who also completed melody discrimination and pretest, improved by an equal amount
      as trained controls on all measures, suggesting that the bulk of learning for the
      control group occurred very rapidly from the pretest. Thirty-one trained
      participants (13 amusics) returned one year later to assess long-term maintenance
      of pitch and melody discrimination. On average, there was no change in
      performance between posttest and one-year follow-up, demonstrating that
      improvements on pitch- and melody-related tasks in amusics and controls can be
      maintained. The findings indicate that amusia is not always a life-long deficit
      when using the current standard diagnostic criteria.

PMID- 29655043
TI  - Patterns of neural response in face regions are predicted by low-level image
      properties.
AB  - Models of face processing suggest that the neural response in different face
      regions is selective for higher-level attributes of the face, such as identity
      and expression. However, it remains unclear to what extent the response in these
      regions can also be explained by more basic organizing principles. Here, we used
      functional magnetic resonance imaging multivariate pattern analysis (fMRI-MVPA)
      to ask whether spatial patterns of response in the core face regions (occipital
      face area - OFA, fusiform face area - FFA, superior temporal sulcus - STS) can be
      predicted across different participants by lower level properties of the
      stimulus. First, we compared the neural response to face identity and viewpoint,
      by showing images of different identities from different viewpoints. The patterns
      of neural response in the core face regions were predicted by the viewpoint, but
      not the identity of the face. Next, we compared the neural response to viewpoint
      and expression, by showing images with different expressions from different
      viewpoints. Again, viewpoint, but not expression, predicted patterns of response
      in face regions. Finally, we show that the effect of viewpoint in both
      experiments could be explained by changes in low-level image properties. Our
      results suggest that a key determinant of the neural representation in these core
      face regions involves lower-level image properties rather than an explicit
      representation of higher-level attributes in the face. The advantage of a
      relatively image-based representation is that it can be used flexibly in the
      perception of faces.

PMID- 29655042
TI  - Supramodal agnosia for oblique mirror orientation in patients with
      periventricular leukomalacia.
AB  - Periventricular leukomalacia (PVL) is characterized by focal necrosis at the
      level of the periventricular white matter, often observed in preterm infants. PVL
      is frequently associated with motor impairment and with visual deficits affecting
      primary stages of visual processes as well as higher visual cognitive abilities.
      Here we describe six PVL subjects, with normal verbal IQ, showing orientation
      perception deficits in both the haptic and visual domains. Subjects were asked to
      compare the orientation of two stimuli presented simultaneously or sequentially,
      using both a two alternative forced choice (2AFC) orientation-discrimination and
      a matching procedure. Visual stimuli were oriented gratings or bars or collinear
      short lines embedded within a random pattern. Haptic stimuli comprised two
      rotatable wooden sticks. PVL patients performed at chance in discriminating the
      oblique orientation, both for visual and haptic stimuli. Moreover when asked to
      reproduce the oblique orientation, they often oriented the stimulus along the
      symmetric mirror orientation. The deficit generalized to stimuli varying in many
      low level features, was invariant for spatiotopic object orientation, and also
      occurred for sequential presentations. The deficit was specific to oblique
      orientations, and not for horizontal or vertical stimuli. These findings show
      that PVL can affect a specific network involved with the supramodal perception of
      mirror symmetry orientation.

PMID- 29655044
TI  - Recommended outcome measures for inpatient rehabilitation of multiple sclerosis
      are not appropriate for the patients with substantially impaired mobility.
AB  - BACKGROUND: In multiple sclerosis (MS) rehabilitation, most currently used
      outcome measures were validated in patients with a relapsing remitting MS and
      mild to moderate impairments. We aimed to assess whether these measures were also
      adequate in more impaired patients, frequently encountered in those with
      progressive MS (PMS). METHODS: Outcome measurements were extracted from medical
      records of 229 patients with PMS undergoing 3 weeks of routine inpatient
      rehabilitation between 2011 and 2015. We assessed the acceptability of Nine-Hole
      Peg Test (9HPT), Timed 25-Foot Walk (T25FW), 2-Minute Walk Test (2MWT), Rivermead
      Mobility Index (RMI) and the Functional Independence Measure (FIM) by analysing
      their statistical distributions, concurrent validity by comparing Spearman
      correlations with pre-specified hypotheses, and responsiveness across impairment
      status by calculating standardized response means. RESULTS: Our concurrent
      validity hypotheses were mainly satisfied. However, all outcome measures had
      skewed distributions, showed low variability, and thus were inadequately
      discriminative. Moreover, 9HPT was never responsive across the impairment states,
      whereas the T25FW was responsive for mildly impaired patients, and the 2MWT for
      mild to moderate MS, respectively. Generic multi-items measures such as RMI and
      FIM-motor were adequately responsive for all severity levels. CONCLUSIONS:
      Currently used outcome measures are inadequate for patients with impaired
      mobility, and there is a dire need of specifically designed outcome measures for
      routine care that are less burdensome and short-term responsive.

PMID- 29655045
TI  - Identification of pre-impact conditions of a cyclist involved in a vehicle
      bicycle accident using an optimized MADYMO reconstruction combined with motion
      capture.
AB  - The aim of the present study was to develop an improved method, using MADYMO
      multi-body simulation software combined with an optimization method and three
      dimensional (3D) motion capture, for identifying the pre-impact conditions of a
      cyclist (walking or cycling) involved in a vehicle-bicycle accident. First, a 3D
      motion capture system was used to analyze coupled motions of a volunteer while
      walking and cycling. The motion capture results were used to define the posture
      of the human model during walking and cycling simulations. Then, cyclist, bicycle
      and vehicle models were developed. Pre-impact parameters of the models were
      treated as unknown design variables. Finally, a multi-objective genetic
      algorithm, the nondominated sorting genetic algorithm II, was used to find
      optimal solutions. The objective functions of the walk parameter were
      significantly lower than cycle parameter; thus, the cyclist was more likely to
      have been walking with the bicycle than riding the bicycle. In the most closely
      matched result found, all observed contact points matched and the injury
      parameters correlated well with the real injuries sustained by the cyclist. Based
      on the real accident reconstruction, the present study indicates that MADYMO
      multi-body simulation software, combined with an optimization method and 3D
      motion capture, can be used to identify the pre-impact conditions of a cyclist
      involved in a vehicle-bicycle accident.

PMID- 29655046
TI  - Enhancing the electrical, optical, and magnetic characteristics of DNA thin films
      through Mn2+ fortification.
AB  - DNA is one of the most propitious biomaterials for use in nanoscience and
      nanotechnology because of its exceptional characteristics, i.e. self-assembly and
      sequence-programmability. In this study, we fabricate sequence-designed double
      crossover (DX) DNA lattices and naturally available salmon DNA (SDNA) thin films
      modified with the transition metal ion Mn2+. Phase transition of DX DNA lattices
      from crystalline to amorphous form controlled by varying the concentration of
      Mn2+ is discussed and a critical transition concentration ([Mn2+]C) is estimated.
      In addition, the electrical, optical, and magnetic properties of Mn2+-modified
      SDNA thin films including current, absorbance, photoluminescence, the X-ray
      photoelectron spectrum, and magnetization are studied to understand their
      conductivity, binding modes, energy transfer characteristics, chemical
      composition, and magnetism. Interestingly, the physical values such as the
      maximum current and photoluminescence, and the minimum absorbance, occur at
      around [Mn2+]C =4 mM, which may be due to the optimal incorporation of Mn2+ into
      the SDNA. The magnetization and susceptibility of SDNA thin films with Mn2+,
      served as magnetic dipoles, are studied under different temperature and magnetic
      field. The magnetization of SDNA thin films with [Mn2+]C shows an S-shaped curve,
      indicating ferromagnetism.

PMID- 29655047
TI  - Effect of surfactant concentration on the evaporation of droplets on cotton
      (Gossypium hirsutum L.) leaves.
AB  - The evaporation kinetics of pesticide droplets deposited on a leaf surface can
      affect their application efficiency. Evaporation of droplets on the hydrophobic
      leaves has received considerable attention, but little is known about hydrophilic
      leaf surfaces. In this study, the effect of surfactant concentration on the
      evaporation of droplets deposited on cotton leaves was investigated. The
      evaporation time is roughly decreased for concentrations ranging from 0% to 0.01%
      and increased from 0.01% to 0.10%. Contrary to the widely held belief that
      pesticide retention on target crops can rapidly be formed only with surfactant
      concentrations exceeding the CMC (critical micelle concentration), this study
      demonstrates that, on hydrophilic cotton leaves, fast evaporation of the droplet
      at surfactant concentrations of 0.01% (CMC) can reduce the volume quickly, lower
      the loss point and enhance pesticide retention. In addition, the evolution of
      droplet volume, height and contact angle on the cotton leaf surface were measured
      to confirm this conclusion. The result presented herein can be used to guide the
      use of surfactants and pesticides in agriculture.

PMID- 29655048
TI  - The problem of 'well' in the term 'Well-being'.

PMID- 29655049
TI  - Delusional disorder in brain abscess: Searching the missing link.

PMID- 29655050
TI  - Aerobic glycolysis and tau deposition in preclinical Alzheimer's disease.
AB  - Research of the human brain metabolism in vivo has largely focused on total
      glucose use (via fluorodeoxyglucose positron emission tomography) and, until
      recently, did not examine the use of glucose outside oxidative phosphorylation,
      which is known as aerobic glycolysis (AG). AG supports important functions
      including biosynthesis and neuroprotection but decreases dramatically with aging.
      This multitracer positron emission tomography study evaluated the relationship
      between AG, total glucose use (CMRGlc), oxygen metabolism (CMRO2), tau, and
      amyloid deposition in 42 individuals, including those at preclinical and
      symptomatic stages of Alzheimer's disease. Our findings demonstrate that in
      individuals with amyloid burden, lower AG is associated with higher tau
      deposition. No such correlation was observed for CMRGlc or CMRO2. We suggest that
      aging-related loss of AG leading to decreased synaptic plasticity and
      neuroprotection may accelerate tauopathy in individuals with amyloid burden.
      Longitudinal AG and Alzheimer's disease pathology studies are needed to verify
      causality.

PMID- 29655051
TI  - Nonlinear pattern of the emergence of white matter hyperintensity in healthy Han
      Chinese: an adult lifespan study.
AB  - White matter hyperintensities (WMHs) are prevalent in the older adult and are
      often accompanied by cognitive decline and an increased risk of dementia.
      However, the roles of WMHs in the periventricular white matter and deep white
      matter regions in the aging process remain controversial. This study aimed to
      investigate the WMH burden across the adult lifespan and determine the
      interrelationships among age, WMH, and cognition. The present study included 312
      healthy individuals aged 21-89 years who received structural magnetic resonance
      imaging and cognitive assessments. Periventricular WMH (PVWMH) and deep WMH
      (DWMH) volumes were computed and fitted using different regression models to
      evaluate the trajectory of WMH changes across the lifespan. Our findings support
      that the changes in WMH volume in the healthy population follow a nonlinear
      pattern with age, especially in PVWMH. With 2-mediator mediation analysis, we
      further suggest that the effect of age on the cognitive performance is mediated
      only by PVWMH. Conclusively, the increased PVWMH, but not DWMH, plays a major
      role in predicting cognitive aging in healthy adults.

PMID- 29655052
TI  - Modeling Possible Inclusion of Pneumococcal Conjugate Vaccine into the National
      Immunization Program for Infants in India.
AB  - BACKGROUND: India is home to up to 28 million infants born annually, and yet to a
      large extent these children do not benefit from the protection provided by a
      pneumococcal conjugate vaccine (PCV) immunization program. The Government of
      India, with support from Gavi, The Vaccine Alliance (in short, Gavi), has
      committed to a pilot implementation of PCV. There are few public health impact
      evaluations available for India, and equally limited epidemiologic data.
      OBJECTIVES: To estimate the potential impact of an infant pneumococcal
      vaccination program in India. METHODS: Using a well-established pneumococcal
      disease impact model parameterized with local data to the extent possible, we
      calculated the potential impact of introducing an infant PCV program in India.
      The model considered direct vaccine protection by PCV10 or PCV13, focusing on
      children younger than 5 years, while varying vaccine uptake according to the
      implementation method (i.e., state-level programs [Gavi funding] or a government
      supported national immunization program [NIP]). RESULTS: With state-level PCV13
      programs comprising 25% uptake across the country, approximately 1.9 million
      cases of pneumococcal disease and approximately 77,000 deaths could be prevented
      annually. An NIP with PCV13 could prevent approximately 7.6 million cases of
      pneumococcal disease and approximately 0.3 million pneumococcal deaths annually,
      compared with no vaccination, considering 100% vaccine uptake. These results are
      likely to have underestimated the additional potential benefits of herd effects
      in unvaccinated children and adults. CONCLUSIONS: Incorporation of PCV into an
      Indian vaccination program for infants is predicted to have a substantially
      positive health impact. Gavi funding of state-level programs is an important step
      toward achieving the full benefits of an NIP in India.

PMID- 29655053
TI  - Molecular interactions of the anticancer agent ellipticine with
      glycosaminoglycans by in silico analysis.
AB  - The anticancer agent ellipticine (ELP) functions as a DNA intercalating drug.
      Depending on the pH of the medium, it exists both in a neutral and a protonated
      form. In acidic extracellular microenvironment characteristic to malignant
      tissues, charged ELP molecules can also bind to glycosaminoglycans (GAGs), linear
      anionic periodic polysaccharides, which interact with various protein targets
      affecting diverse cellular events. Although a previous experimental work
      indicated specific GAG binding of protonated ELP, the underlying molecular
      mechanisms remain to be elucidated. From a computational point of view, analysis
      of molecular systems containing GAGs is challenging due to their high
      flexibility, variability in sulfation patterns and a key role of electrostatics
      and solvent-mediated interactions. In the present study, molecular dynamics-based
      approaches were employed to model ELP-GAG interactions in order to unveil the
      atomistic details of this biologically relevant molecular system. We
      characterized dynamic and energetic properties of three kinds of ELP-GAG
      complexes to rationalize and complement the available experimental data. The
      results reported herein provide insight into possible molecular pathways by which
      biological actions of ELP are mediated.

PMID- 29655055
TI  - Geniposide improves hepatic inflammation in diabetic db/db mice.
AB  - The current study was designed to investigate the protective role of geniposide
      (GE) in liver injury in diabetic C57BL/KsJ-db/db mice and to explore the
      underlying mechanisms. The oral glucose tolerance test was performed, and the
      levels of insulin, alanine aminotransferase (ALT), aspartate aminotransaminase
      (AST), total cholesterol (TC) and triglyceride (TG) were determined. The levels
      of the pro-inflammatory cytokines interleukin (IL)-1beta, IL-6 and tumour
      necrosis factor-alpha were decreased by GE, metformin and fasudil in diabetic
      db/db mice. Western blotting analysis showed that the expression levels of Rho,
      ROCK1, ROCK2, p-NF-kappaBp65 and p-IkappaBalpha were significantly reversed by GE
      treatment. These findings demonstrated that GE exhibits a protective effect on
      diabetic hepatic inflammation.

PMID- 29655054
TI  - Oregonin inhibits inflammation and protects against barrier disruption in
      intestinal epithelial cells.
AB  - BACKGROUND AND AIMS: Oregonin, a major diarylheptanoid derivative isolated from
      Alnus japonica, exerts anti-inflammatory effects; however, little is known about
      the effect of oregonin in intestinal inflammation. The current study investigated
      the potential of oregonin for clinical applications in the treatment of
      inflammatory bowel disease (IBD) and elucidated its underlying molecular
      mechanisms. METHODS: The anti-inflammatory effect of oregonin in tumor necrosis
      factor-alpha (TNF-alpha)-stimulated human intestinal epithelial HT-29 cells was
      investigated. In addition, the protective effect of oregonin was determined
      against disruption of the intestinal barrier in tert-butyl hydroperoxide (t-BH)
      stimulated human intestinal epithelial Caco-2 cells. RESULTS: Oregonin suppressed
      the expression of cyclooxygenase-2 (COX-2), intercellular adhesion molecule-1
      (ICAM-1), IL-8, and IL-1beta, and inhibited activation of nuclear factor kappaB
      (NF-kappaB) in HT-29 cells stimulated with TNF-alpha. Oregonin increased heme
      oxygenase-1 (HO-1) expression through the ERK1/2 and JNK-dependent signaling
      pathway, which contributed to the oregonin-mediated suppression of COX-2
      expression in the HT-29 cells stimulated with TNF-alpha. Moreover, oregonin
      induced AMP-activated protein kinase (AMPK) activation. Knockdown of AMPK
      abolished the induction of HO-1 protein by oregonin and suppression of oregonin
      mediated ICAM-1 and COX-2 expression in the HT-29 cells stimulated with TNF
      alpha. Oregonin prevented the t-BH-induced increase in monolayer permeability
      through inhibition of the reduction in expression of zonula occludens-1 and
      occludin in Caco-2 cells. Targeting HO-1 by siRNA transfection attenuated the
      oregonin-mediated prevention of loss of tight junction proteins and increase in
      permeability. CONCLUSION: The findings of this study suggest that oregonin is a
      potential candidate for treatment of IBD by preventing mucosal inflammation and
      barrier disruption.

PMID- 29655056
TI  - IL-17 inhibits the accumulation of myeloid-derived suppressor cells in breast
      cancer via activating STAT3.
AB  - Breast cancer (BC) is one of the most common cancers, with high recurrence rate
      and poor prognosis of recurrent metastatic disease. In our study, we analyzed the
      markers and development of markers of myeloid-derived suppressor cells (MDSCs)
      for BC progression and occurrence. MDSCs is one of the major orchestrators of the
      immunosuppressive network, are associated with immune suppression and considered
      a prime target for cancer immunotherapy. Interleukin-17 (IL-17) is a signature
      cytokine of Th17 cells. Previous research has indicated that IL-17 plays a
      proinflammatory role. It was found to increase frequencies at certain tumors and
      involved in angiogenesis. This study aims to elucidate the biological role of IL
      17 on MDSC in BC cells. Expression of MDSC in peripheral blood of 80 BCE patients
      and 20 healthy volunteers was compared. Our results indicate that MDSC numbers in
      patients with BC were higher than healthy donors. Moreover, the clinical grade
      and prognosis were correlate with the number of MDSC. In this study, we
      investigated the effect of IL-17 on MDSCs. CCK-8 assay and flow cytometry were
      used to assess the proliferation and apoptosis of cells. The expression of key
      MDSC-related molecules was detected by western blotting. We identified
      administration with IL-17 in vitro significantly induced MDSC differentiation,
      inhibited their proliferation and triggered apoptosis. In addition, Low IL-17
      inhibited the activation of STAT3, leading to increase formation of MDSCs in BC.
      Our results from experiments suggest that the effects of IL-17 mediate activation
      of STAT3 signaling in BC cells. Taken together, our study shows that MDSCs can be
      a new type prognostic marker in BC patient. Targeting IL-17/Stat3 signaling may
      be a promising strategy for BC treatment.

PMID- 29655057
TI  - Isolation, identification and characterization of apigenin from Justicia
      gendarussa and its anti-inflammatory activity.
AB  - Inflammatory responses during chronic diseases such as atherosclerosis, cancer
      etc., are harmful to host organisms. Generally NSAIDs are used to treat against
      these severe conditions but due to its adverse effects studies are going on with
      medicinal plants, since they are rich in bioactive compounds. Justicia gendarussa
      is one such plant which has been used as a remedial measure for treating
      inflammatory diseases since ancient time. Thus the present study involved in the
      isolation, characterization and identification of apigenin (flavonoid) from this
      plant and to elucidate its molecular mechanism against inflammation via TLR-NF
      kappaB signaling pathway using ox-LDL induced hPBMCs in in vitro model.
      Methanolic extract was used for the isolation process and results showed that the
      F6 fraction collected from ethyl acetate through column chromatography showed 89%
      paw edema inhibition at a dose of 10 mg/kg in carrageenan induced rats.
      Purification of F6 by TLC with toluene: chloroform: acetone (8:5:7) and further
      characterization by 1HNMR indicated the presence of bioactive compound, apigenin.
      In vitro studies revealed that pretreatment of ox-LDL induced hPBMCs with
      apigenin (25 MUM) significantly (P < 0.05) reduced the levels of TLR4, MyD88,
      TRIF, TRAF6, NF-kappaB, COX-2, PGE2, IL-1beta and TNF-alpha responsible for
      generating inflammation and elevated the level of anti-inflammatory cytokine, IL
      10. These results indicate the therapeutic efficacy of bioflavonoid apigenin
      which was isolated from Justicia gendarussa against ox-LDL induced inflammation.
      Therefore apigenin can be treated as a suitable therapeutic agent against
      inflammatory diseases.

PMID- 29655058
TI  - The protective effect of Lactobacillus and Bifidobacterium as the gut microbiota
      members against chronic urticaria.
AB  - BACKGROUND: Chronic Urticaria is a common disorder which is defined by recurrent
      occurrence of wheals and sometimes angioedema. It has a notable influence on the
      patients' quality of life. Regulation of the immune system is one of the
      important roles of the gut microbiota. The effect of dysbiosis considering some
      members of gut microbiota in patients with chronic urticaria has been
      demonstrated in our previous study. OBJECTIVE: Comparing the frequency and
      bacterial load of Lactobacillus, Bifidobacterium, and Bacteroides between
      patients with chronic urticaria and healthy controls. METHODS: 20 patients with
      chronic urticaria and 20 age and sex matched healthy individuals were included in
      the present study. Stool samples were analyzed for determining the frequency and
      bacterial load of Lactobacillus, Bifidobacterium, and Bacteroides genera.
      RESULTS: There were no significant differences among the frequencies of
      detectable Lactobacillus, Bifidobacterium, or Bacteroides in stool samples of
      patients with chronic urticaria and healthy controls. The relative amounts of
      Lactobacillus and Bifidobacterium were significantly higher in fecal samples from
      controls compared to patients with chronic urticaria (P = 0.038 and 0.039,
      respectively). CONCLUSION: It is the first study on the implication of
      Lactobacillus, Bifidobacterium, and Bacteroides genera as gut microbiota members
      in patients with chronic urticaria.

PMID- 29655059
TI  - Examining implicit cognitions in the evaluation of a community-wide physical
      activity program.
AB  - The purpose of this study was to incorporate measures of attentional bias and
      implicit attitudes in the evaluation of a community-wide physical activity
      program, UWALK, by examining the relationships among proximal, intermediate, and
      distal outcomes of the program as outlined in the hierarchy of effects model.
      UWALK incorporated various communication and marketing strategies via mass media,
      on- and off-line platforms. Participants (N = 127) reported unprompted then
      prompted awareness of UWALK followed by measures of attentional bias and implicit
      attitudes, watched a 30-second UWALK video, then completed a thought listing task
      and questionnaires measuring instrumental and affective attitudes, leisure time
      physical activity, and demographics. Results showed that participants with
      unprompted awareness of UWALK demonstrated attentional bias toward UWALK images,
      positive implicit attitudes, and greater physical activity participation compared
      to unaware counterparts. Attentional bias, awareness, and implicit attitudes
      significantly predicted behavior, accounting for 15.2% of the variance. This
      study emphasizes the importance of including measures of automatic cognitions
      during evaluation can further inform the effects of a program. The results also
      showed that it is problematic to assume that visiting a website indicates a
      program will be remembered and related cognitions will be affected.

PMID- 29655060
TI  - Elevated cancer risk in Holocaust survivors residing in Israel: A retrospective
      cohort study.
AB  - BACKGROUND: The purpose of this study was to examine the incidence of malignant
      diseases among Holocaust survivors in Israel compared with European and American
      immigrants who did not experience the Holocaust. METHODS: Study subjects included
      Holocaust survivors born in European countries under Nazi occupation before 1945,
      who immigrated to Israel after 1945 and were alive as of the year 2000. Living
      survivors were identified based on recognition criteria in accordance with the
      Holocaust Survivor Benefits Law. The comparison group consisted of Clalit
      enrollees who were born before 1945 in European countries not under Nazi
      occupation and were alive in 2000 or were born in any European country or
      America, immigrated to Israel before 1939 and were alive in 2000. The incidence
      of malignant diseases was compared in univariate and Poisson regression models
      analyses, controlling for age, smoking, obesity, diabetes and place of residence.
      RESULTS: The study included 294,543 Holocaust survivors, and the mean age at the
      beginning of follow-up was 74 +/- 8.7 years; 43% males. In multivariable
      analyses, the rate ratio (RR) values for males and females were 1.9 and 1.3 for
      colon cancer, 1.9 and 1.4 for lung cancer, 1.6 and 1.4 for bladder cancer and 1.2
      and 1.3 for melanoma, respectively. For prostate cancer in males, the RR was 1.4,
      while for breast cancer in females, it was 1.2. CONCLUSIONS: The incidence of
      malignant diseases among Holocaust survivors residing in Israel was higher than
      that among non-Holocaust survivors. These associations remained statistically
      significant in a multivariable analysis and were stronger for males.

PMID- 29655061
TI  - Endocrine therapy or chemotherapy as first-line therapy in hormone receptor
      positive HER2-negative metastatic breast cancer patients.
AB  - BACKGROUND: For hormone receptor-positive (HR+) human epidermal growth factor
      receptor 2 (HER2-) negative metastatic breast cancer (MBC), international
      guidelines recommend endocrine therapy as first-line treatment, except in case of
      'visceral crisis'. In the latter case, chemotherapy is preferred. Few studies
      have compared these two strategies. We used the Epidemiological Strategy and
      Medical Economics (ESME) programme, UNICANCER, a large national observational
      database (NCT03275311), to address this question. METHODS: All patients who
      initiated treatment for a newly diagnosed HR+ HER2-negative MBC between January
      2008 and December 2014 in any of the 18 French Comprehensive Cancer Centers
      participating to ESME were selected. Patients should be aromatase inhibitor (AI)
      sensitive (no previous AI or relapse occurring more than 1 year after last
      adjuvant AI). Objectives of the study were evaluation of progression-free and
      overall survival (OS) according to the type of first-line treatment adjusted on
      main prognostic factors using a propensity score. RESULTS: Six thousand two
      hundred sixty-five patients were selected: 2733 (43.6%) received endocrine
      therapy alone, while 3532 (56.4%) received chemotherapy as first-line therapy.
      Among the latter, 2073 (58.7%) received maintenance endocrine therapy. Median OS
      was 60.78 months (95% confidence interval [CI], 57.16-64.09) and 49.64 months
      (95% CI, 47.31-51.64; p < 0.0001) for patients receiving endocrine therapy alone
      and chemotherapy +/- maintenance endocrine therapy, respectively. However, this
      difference was not significant after adjusting on the propensity score (hazard
      ratio: 0.943, 95% CI 0.863-1.030, p = 0.19). CONCLUSION: In this large
      retrospective cohort of patients with AI-sensitive metastatic luminal BC, OS was
      similar, whether first-line treatment was chemotherapy or endocrine therapy. In
      agreement with international guidelines, endocrine therapy should be the first
      choice for first-line systemic treatment for MBC in the absence of visceral
      crisis.

PMID- 29655062
TI  - Implicit and explicit anti-fat bias: The role of weight-related attitudes and
      beliefs.
AB  - INTRODUCTION: The increasing prevalence of anti-fat bias in American society
      comes at a great cost to the health and well-being of people who are overweight
      or obese. A better understanding of the correlates of anti-fat bias would inform
      development of interventions for reducing anti-fat bias. Based on three
      theoretical perspectives, this study tested the relation between attitudes and
      beliefs about weight and anti-fat bias (implicit and explicit): (1) The belief
      that one is like people who are fat (social identity theory). (2) The belief that
      one can control her/his weight (attribution theory). And (3) the beliefs that
      most people prefer thin people and that weight is important (socio-cultural
      theory). METHODS: Participants were 66,799 volunteers (47,265 women, mean age of
      27.88 +/- 11.9 years) who completed the Thin-Fat Implicit Association Test on the
      Project Implicit website (https://implicit.harvard.edu/) during 2016. Explicit
      anti-fat bias and weight-related attitudes and beliefs were assessed by self
      report. Correlation and regression analyses were conducted to examine links
      between weight-related attitudes and beliefs and anti-fat bias. RESULTS: All
      tested weight-related attitudes and beliefs were significantly (p < .001)
      correlated with explicit and implicit anti-fat bias, but some of the correlations
      were very weak. An examination of the relative contribution of the tested weight
      related attitudes and beliefs to a model explaining anti-fat bias suggested that
      the strongest correlates of explicit anti-fat bias were the beliefs that weight
      was important (beta = 0.194, p < .001), that most people prefer thin people (beta
      = 0.177, p < .001), and that the respondent was like people who are fat (beta = 
      0.180, p < .001). DISCUSSION: The social-identity and socio-cultural theories may
      provide a stronger explanation for anti-fat bias relative to attribution theory.
      Future research could use longitudinal designs with more reliable measures in
      order to verify these cross-sectional findings.

PMID- 29655063
TI  - Acetabular labral tear description and measures of pincer and cam-type
      femoroacetabular impingement and interobserver variability on 3 T MR arthrograms.
AB  - PURPOSE: To evaluate the inter-rater agreement for description of labral tears
      and measures of femoroacetabular impingement (FAI) on 3 T hip MR arthrography.
      MATERIALS AND METHODS: 53 hip MR arthrograms were reviewed by three
      musculoskeletal radiologists. Labral tears were described (Czerny classification)
      with extents recorded. Cam- and pincer-type FAI measures were performed.
      Intraclass correlation (ICC) and kappa statistic (kappa) assessed inter-observer
      agreement. RESULTS: There was fair agreement for labral tear description (kappa =
      0.25-0.39) and for alpha angles (ICC = 0.54), and fair to excellent agreement for
      other measures of FAI (ICC = 0.51-0.90). CONCLUSION: There is moderate inter
      observer variability reporting labral tears and measures of FAI.

PMID- 29655064
TI  - Estimation of p,p'-DDT degradation in soil by modeling and constraining
      hydrological and biogeochemical controls.
AB  - Despite not being used for decades in most countries, DDT remains ubiquitous in
      soils due to its persistence and intense past usage. Because of this it is still
      a pollutant of high global concern. Assessing long term dissipation of DDT from
      this reservoir is fundamental to understand future environmental and human
      exposure. Despite a large research effort, key properties controlling fate in
      soil (in particular, the degradation half-life (tausoil)) are far from being
      fully quantified. This paper describes a case study in a large central European
      catchment where hundreds of measurements of p,p'-DDT concentrations in air, soil,
      river water and sediment are available for the last two decades. The goal was to
      deliver an integrated estimation of tausoil by constraining a state-of-the-art
      hydrobiogeochemical-multimedia fate model of the catchment against the full body
      of empirical data available for this area. The INCA-Contaminants model was used
      for this scope. Good predictive performance against an (external) dataset of
      water and sediment concentrations was achieved with partitioning properties taken
      from the literature and tausoil estimates obtained from forcing the model against
      empirical historical data of p,p'-DDT in the catchment multicompartments. This
      approach allowed estimation of p,p'-DDT degradation in soil after taking adequate
      consideration of losses due to runoff and volatilization. Estimated tausoil
      ranged over 3000-3800 days. Degradation was the most important loss process,
      accounting on a yearly basis for more than 90% of the total dissipation. The
      total dissipation flux from the catchment soils was one order of magnitude higher
      than the total current atmospheric input estimated from atmospheric
      concentrations, suggesting that the bulk of p,p'-DDT currently being remobilized
      or lost is essentially that accumulated over two decades ago.

PMID- 29655065
TI  - In situ microbiota distinguished primary anthropogenic stressor in freshwater
      sediments.
AB  - Conventional assessment and evaluation of sediment quality are based on
      laboratory-based ecotoxicological and chemical measurements with lack of concern
      for ecological relevance. Microbiotas in sediment are responsive to pollutants
      and can be used as alternative ecological indicators of sediment pollutants;
      however, the linkage between the microbial ecology and ecotoxicological endpoints
      in response to sediment contamination has been poorly evaluated. Here, in situ
      microbiotas from the Three Gorges Reservoir (TGR) area of the Yangtze River were
      characterized by DNA metabarcoding approaches, and then, changes of in situ
      microbiotas were compared with the ecotoxicological endpoint, aryl hydrocarbon
      receptor (AhR) mediated activity, and level of polycyclic aromatic hydrocarbons
      (PAHs) in sediments. PAHs and organic pollutant mixtures mediating AhR activity
      had different effects on the structures of microbiotas. Specifically, Shannon
      indices of protistan communities were negatively correlated with the levels of
      AhR mediated activity and PAHs. The sediment AhR activity was positively
      correlated with the relative abundance of prokaryotic Acetobacteraceae, but had a
      negative correlation with protistan Oxytrichidae. Furthermore, a quantitative
      classification model was built to predict the level of AhR activity based on the
      relative abundances of Acetobacteraceae and Oxytrichidae. These results suggested
      that in situ Protista communities could provide a useful tool for monitoring and
      assessing ecological stressors. The observed responses of microbial community
      provided supplementary evidence to support that the AhR-active pollutants, such
      as PAHs, were the primary stressors of the aquatic community in TGR area.

PMID- 29655067
TI  - Contrasting effects of photochemical and microbial degradation on Cu(II) binding
      with fluorescent DOM from different origins.
AB  - Effects of photochemical and microbial degradation on variations in composition
      and molecular-size of dissolved organic matter (DOM) from different sources
      (algal and soil) and the subsequent influence on Cu(II) binding were investigated
      using UV-Vis, fluorescence excitation-emission matrices coupled with parallel
      factor analysis, flow field-flow fractionation (FlFFF), and metal titration. The
      degradation processes resulted in an initial rapid decline in the bulk dissolved
      organic carbon and chromophoric and fluorescent DOM components, followed by a
      small or little decrease. Specifically, photochemical reaction decreased the
      aromaticity, humification and apparent molecular weights of all DOM samples,
      whereas a reverse trend was observed during microbial degradation. The FlFFF
      fractograms revealed that coagulation of both protein- and humic-like DOM induced
      an increase in molecular weights for algal-DOM, while the molecular weight
      enhancement for allochthonous soil samples was mainly attributed to the self
      assembly of humic-like components. The Cu(II) binding capacity of algal-derived
      humic-like and fulvic-like DOM consistently increased during photo- and bio
      degradation, while the soil-derived DOM exhibited a slight decline in Cu(II)
      binding capacity during photo-degradation but a substantial increase during
      microbial degradation, indicating source- and degradation-dependent metal binding
      heterogeneities. Pearson correlation analysis demonstrated that the Cu(II)
      binding potential was mostly related with aromaticity and molecular size for
      allochthonous soil-derived DOM, but was regulated by both DOM properties and
      specific degradation processes for autochthonous algal-derived DOM. This study
      highlighted the coupling role of inherent DOM properties and external
      environmental processes in regulating metal binding, and provided new insights
      into metal-DOM interactions and the behavior and fate of DOM-bound metals in
      aquatic environments.

PMID- 29655066
TI  - Distribution and availability of cadmium in profile and aggregates of a paddy
      soil with 30-year fertilization and its impact on Cd accumulation in rice plant.
AB  - The research was conducted to investigate the accumulation, distribution and
      availability of Cd in paddy soil and their relation to Cd in rice plants under 30
      year fertilization regimes. Six treatments were involved in the study: control
      without fertilization (CK), chemical fertilizer (NPK), high nitrogen chemical
      fertilizer (HN), rice straw incorporation (ST), low and high dosage of manure
      fertilizer (LM and HM). Total and DTPA extractable concentration of Cd (T-Cd and
      DTPA-Cd) in bulk soils (20 cm topsoil), profiles (0-60 cm) and aggregates (>2, 1
      2, 0.5-1, 0.25-0.5, 0.053-0.25 and < 0.053 mm) were investigated. The Cd
      concentration in relevant rice plant (roots, stems, leaves, husks and grains)
      were also analyzed. Manure fertilizers caused T-Cd accumulation in bulk soil with
      a significant increase of 36.2% in LM and 81.2% in HM. Similar impacts of manure
      fertilizers were observed in DTPA-Cd in the bulk soil. Further, the HM generated
      a further accumulation in deeper soil layers, presenting a remarkable increase of
      T-Cd (28.3%-225%) in 10-40 cm and DTPA-Cd (116%-158%) in 10-30 cm profiles.
      Moreover, the continuous application of manure fertilizers enhanced the
      availability of Cd in all aggregate size classes with an increase of 17.3%-87.8%
      in DTPA-Cd. Organic fertilizers (LM, HM and ST) heightened the content of Cd
      (38.0%-152%) in all parts of rice plant. The accumulation of Cd in rice plants
      was directly affected by fertilization regimes and Cd availability in the 10-20
      cm soil layers and 0.25-0.5 mm aggregates. In conclusion, long-term application
      of manures resulted in increasing availability of Cd in aggregates and in topsoil
      and subsoil layers, which accordingly enhanced the accumulation of Cd in rice
      plants.

PMID- 29655068
TI  - Two forage fishes as potential conduits for the vertical transfer of microfibres
      in Northeastern Pacific Ocean food webs.
AB  - We assessed the potential role played by two vital Northeastern Pacific Ocean
      forage fishes, the Pacific sand lance (Ammodytes personatus) and Pacific herring
      (Clupea pallasii), as conduits for the vertical transfer of microfibres in food
      webs. We quantified the number of microfibres found in the stomachs of 734 sand
      lance and 205 herring that had been captured by an abundant seabird, the
      rhinoceros auklet (Cerorhinca monocerata). Sampling took place on six widely
      dispersed breeding colonies in British Columbia, Canada, and Washington State,
      USA, over one to eight years. The North Pacific Ocean is a global hotspot for
      pollution, yet few sand lance (1.5%) or herring (2.0%) had ingested microfibres.
      In addition, there was no systematic relationship between the prevalence of
      microplastics in the fish stomachs vs. in waters around three of our study
      colonies (measured in an earlier study). Sampling at a single site (Protection
      Island, WA) in a single year (2016) yielded most (sand lance) or all (herring) of
      the microfibres recovered over the 30 colony-years of sampling involved in this
      study, yet no microfibres had been recovered there, in either species, in the
      previous year. We thus found no evidence that sand lance and herring currently
      act as major food-web conduits for microfibres along British Columbia's outer
      coast, nor that the local at-sea density of plastic necessarily determines how
      much plastic enters marine food webs via zooplanktivores. Extensive urban
      development around the Salish Sea probably explains the elevated microfibre loads
      in fishes collected on Protection Island, but we cannot account for the between
      year variation. Nonetheless, the existence of such marked interannual variation
      indicates the importance of measuring year-to-year variation in microfibre
      pollution both at sea and in marine biota.

PMID- 29655069
TI  - Development of a clinical prediction rule to identify patients with plantar heel
      pain likely to benefit from biomechanical anti-pronation taping: A prospective
      cohort study.
AB  - OBJECTIVES: To develop a clinical prediction rule (CPR) to identify patients with
      plantar heel pain (PHP) likely to benefit from biomechanical anti-pronation
      taping (BAPT). DESIGN: A prospective cohort study. SETTING: An outpatient
      rehabilitation department in a general hospital. PARTICIPANTS: Seventy-five
      patients with PHP. MAIN OUTCOME MEASURES: After completing a series of physical
      examinations, all patients received BAPT and were evaluated with a numeric rating
      scale for pain intensity, the patient-specific functional scale and foot function
      index (FFI) for function, and the global rating of change for perceived
      improvement. RESULTS: Twenty-eight patients achieved a successful outcome. A CPR
      with 6 significant variables was identified by a multivariate logistic
      regression: FFI score less than 33.3, hip adduction angle of the most affected
      side was greater than the contralateral side, ankle plantarflexors and hip
      abductors on the most affected side were not weaker than those on the
      contralateral side, ankle invertors on the most affected side were weaker than
      the contralateral side, and having more than 2 painful sites in the low back and
      lower extremity regions. If 5 or more of the 6 predictors were presented, the
      probability of success increased from 37% to 80%. CONCLUSIONS: A CPR has been
      developed to identify patients with PHP likely to benefit from BAPT.

PMID- 29655070
TI  - Development and external validation of a prediction rule for an unfavorable
      course of late-life depression: A multicenter cohort study.
AB  - BACKGROUND: Given the poor prognosis of late-life depression, it is crucial to
      identify those at risk. Our objective was to construct and validate a prediction
      rule for an unfavourable course of late-life depression. METHODS: For development
      and internal validation of the model, we used The Netherlands Study of Depression
      in Older Persons (NESDO) data. We included participants with a major depressive
      disorder (MDD) at baseline (n = 270; 60-90 years), assessed with the Composite
      International Diagnostic Interview (CIDI). For external validation of the model,
      we used The Netherlands Study of Depression and Anxiety (NESDA) data (n = 197; 50
      66 years). The outcome was MDD after 2 years of follow-up, assessed with the
      CIDI. Candidate predictors concerned sociodemographics, psychopathology, physical
      symptoms, medication, psychological determinants, and healthcare setting. Model
      performance was assessed by calculating calibration and discrimination. RESULTS:
      111 subjects (41.1%) had MDD after 2 years of follow-up. Independent predictors
      of MDD after 2 years were (older) age, (early) onset of depression, severity of
      depression, anxiety symptoms, comorbid anxiety disorder, fatigue, and loneliness.
      The final model showed good calibration and reasonable discrimination (AUC of
      0.75; 0.70 after external validation). The strongest individual predictor was
      severity of depression (AUC of 0.69; 0.68 after external validation).
      LIMITATIONS: The model was developed and validated in The Netherlands, which
      could affect the cross-country generalizability. CONCLUSIONS: Based on rather
      simple clinical indicators, it is possible to predict the 2-year course of MDD.
      The prediction rule can be used for monitoring MDD patients and identifying those
      at risk of an unfavourable outcome.

PMID- 29655071
TI  - EEG gamma synchronization is associated with response to paroxetine treatment.
AB  - BACKGROUND: Resistance to medication is a significant problem in psychiatric
      practice, and effective methods for predicting response are needed to optimize
      treatment efficacy and limit morbidity. Gamma oscillations are considered as an
      index of the brain's general cognitive activity; however, the role of gamma
      oscillations in disease has not been studied sufficiently. AIM: This study aimed
      to determine if gamma power during rest can be used to predict response to anti
      depressant medication treatment. METHOD: Hamilton Depression Rating Scale (HDRS)
      score and resting state gamma power was measured in 18 medication-free patients
      during an episode of major depression. After 6 weeks of paroxetine monotherapy
      HDRS was administered again. RESULTS: Baseline gamma power at frontal, central
      and temporal electrodes before treatment was significantly related to post
      treatment change in HDRS scores. CONCLUSION: The results indicate that gamma
      oscillations could be considered a marker of response to paroxetine treatment in
      patients with major depression.

PMID- 29655072
TI  - The course of anxiety in persons with dementia in Norwegian nursing homes: A 12
      month follow-up study.
AB  - BACKGROUND: Knowledge is scarce about the course of anxiety in persons with
      dementia (PWD) in nursing homes. This study aimed to describe the course of
      anxiety, anxiety symptoms, and the correlates of change in the Norwegian version
      of the Rating Anxiety in Dementia scale (RAID-N) score in PWD in nursing homes.
      METHODS: Using the RAID-N, anxiety was assessed in 298 PWD aged 65 years and
      above from 17 Norwegian nursing homes. The assessments were made at baseline and
      after a mean follow-up period of 350 days (SD 12.3). Associations between the
      change in RAID-N score and demographic and clinical characteristics were analyzed
      with multilevel regression models. RESULTS: At 12 months, 93 participants (31.2%)
      had died. There was no significant change in the proportion of participants with
      anxiety, defined as RAID-N score >=12, from baseline (33.7%) to follow-up (31.2%)
      (McNemar, p = 0.597). "Motor tension", "frightened and anxious", and
      "irritability" were the most frequent anxiety symptoms among those with dementia
      and anxiety. A higher Neuropsychiatric Inventory-Questionnaire (NPI-Q) sub
      syndrome affective baseline score and more use of anxiolytics were associated
      with reduction in RAID-N score, whereas a higher NPI-Q sub-syndrome aroused
      baseline score and more use of antipsychotics were associated with an increase in
      RAID-N score at follow-up. LIMITATIONS: The study did not control for ongoing
      treatment or changes of comorbidities. CONCLUSIONS: Anxiety and anxiety symptoms
      are highly prevalent among PWD in nursing homes over a12-month period. The
      symptoms "motor tension", "frightened and anxious", and "irritability" require
      attention in screening for anxiety.

PMID- 29655073
TI  - Neither all anti-inflammatory drugs nor all doses are effective in accelerating
      the antidepressant-like effect of fluoxetine in an animal model of depression.
AB  - INTRODUCTION: Non-steroidal anti-inflammatory drugs (NSAIDs) have been studied as
      possible adjunctive therapy in the treatment of depression. However,
      administering NSAIDs to increase the effectiveness of antidepressant has yielded
      inconsistent results. METHODS: We evaluated the effect of the co-administration
      of fluoxetine (5 mg/kg) and flurbiprofen (5 mg/kg) or fluoxetine (5 mg/kg) and
      celecoxib (5 mg/kg) in the chronic escape deficit (CED) model of depression after
      7 days of treatment. The co-administration of fluoxetine plus acetylsalicylic
      acid (ASA, 45 mg/kg i.p.) was used as a positive control. Moreover, we tested the
      behavioral effect of different doses (45, 22.5, and 11.25 mg/Kg i.p.) of ASA as
      potentiating agent of the effect of fluoxetine in the same paradigm. RESULTS: Our
      study showed that only the co-administration of ASA with fluoxetine was able to
      revert the stress-induced condition of escape deficit after 7 days of treatment,
      and that the amplitude of the antidepressant-like effect of ASA was dose
      dependent. In the same experimental conditions, celecoxib with fluoxetine only
      partially resolved the stress-induced impaired behavior while
      flurbiprofen/fluoxetine cotreatment was ineffective. LIMITATIONS: Our study is
      still exploratory, more doses, longer treatment regimens, and different
      behavioral outcomes must be investigated to draw a clear conclusion. CONCLUSION:
      Our results further stress the importance of the type and dose when NSAIDs are
      associated with antidepressants to ameliorate a clinical response.

PMID- 29655074
TI  - The role of cognitive impairment in psychosocial functioning in remitted
      depression.
AB  - BACKGROUND: Cognitive dysfunction is a prevalent and disabling symptom of Major
      Depressive Disorder (MDD), and is often retained in the remitted stage of
      illness. Emerging evidence suggests that cognitive impairment may be associated
      with dysfunction in a number of psychosocial domains (e.g., workplace
      productivity, social relationships). The current study explored the relationship
      between cognition and psychosocial functioning in remitted MDD and in healthy
      controls. METHODS: Data were obtained from 182 participants of the Cognitive
      Function and Mood Study (CoFaM-S), a cross-sectional study of cognition, mood,
      and social cognition in mood disorders. Participants' (Remitted MDD n = 72,
      Healthy n = 110) cognition was assessed with a battery of cognitive tests
      including the Repeatable Battery for the Assessment of Neuropsychological
      Function (RBANS) and other standard measures of cognition (e.g., The Tower of
      London task). Psychosocial functioning was clinically evaluated with the
      Functioning Assessment Short Test (FAST). RESULTS: The results indicated that
      executive functioning was the strongest independent predictor of functioning in
      remitted MDD patients, whereas various cognitive domains predicted psychosocial
      functioning in healthy individuals. LIMITATIONS: Psychosocial functioning was
      measured with a clinical interview, and was therefore reliant on clinicians'
      judgement of impairment, as opposed to more objective measures of functioning.
      CONCLUSIONS: These findings suggest that executive cognition plays an important
      role in functional recovery in remitted depression, and may be a crucial target
      in adjunctive treatment.

PMID- 29655075
TI  - Prevalence, risk factors and clinical characteristics of suicidal ideation in
      Chinese patients with depression.
AB  - BACKGROUND: Suicide risk is greatly increased in depression. Detection of those
      at risk is clinically important. Hence, this study aimed to evaluate the
      prevalence and identify independent risk factors associated with suicidal
      ideation (SI) in a widespread symptomatology within and outside DSM framework.
      METHODS: This study was part of the National Survey on Symptomatology of
      Depression (NSSD) which was designed to investigate the magnitude of symptoms of
      current major depressive episode in China. Stepwise multivariable logistic
      regression was performed to examine the independent risk factors for SI,
      including variables that are statistically significant in univariate analysis.
      Receiver operating characteristic (ROC) was used to evaluate the performance of
      the regression model. RESULTS: A total of 3275 patients (1293 males and 1982
      females) were included in our analysis. Of these, 1750 patients (53.4%) had SI.
      Independent risk predictors included crying (P = 0.000; odds ratio = 1.827),
      helplessness (P = 0.000; odds ratio = 1.514), worthlessness (P = 0.001; odds
      ratio = 1.359), hopelessness (P = 0.000; odds ratio = 1.805), unusually restless
      (P = 0.005; odds ratio = 1.276), self-harm (P = 0.000; odds ratio = 3.385), mood
      incongruent psychosis (P = 0.000; odds ratio = 2.782), feeling losing control of
      oneself (P = 0.009; odds ratio = 1.352), hypersomnia (P = 0.000; odds ratio =
      1.805), sensory system complaints (P = 0.000; odds ratio = 1.546), derealization
      (P = 0.006; odds ratio = 1.580), guilt (P = 0.002; odds ratio = 1.332), suicidal
      attempts (P = 0.000; odds ratio = 2.841), male gender (P = 0.001; odds ratio =
      0.756), the total course of depression (P = 0.010; odds ratio = 1.003) in the
      regression model. In addition, the areas under the curve of the ROC and the
      accuracy for the regression model were 0.80 and 0.76, respectively. CONCLUSIONS:
      This study provided an effective risk model for SI in MDD and indicated that all
      these factors in our model allow better the employment of preventative measures.

PMID- 29655076
TI  - Psychometric properties of the social anxiety subscale of the Youth Anxiety
      Measure for DSM-5 (YAM-5-I-SAD) in a clinical sample of Spanish-speaking
      adolescents.
AB  - BACKGROUND: The Youth Anxiety Measure-I for DSM-5 has recently been developed to
      assess youth's anxiety symptomatology. As social anxiety is one of the most
      common disorders in adolescence, this scale includes a subscale measuring social
      anxiety. However, psychometric properties of the YAM-5-I social anxiety subscale
      (YAM-5-I-SAD) in clinical samples are lacking. This paper aims to bridge the gap.
      METHODS: The sample comprised 24 clinically diagnosed and 24 healthy control
      Spanish-speaking adolescents aged 14-17 years. RESULTS: Data revealed that the
      YAM-5- I-SAD yielded excellent sensitivity, which makes it particularly useful as
      a screening tool to early detect socially anxious adolescents. In addition, the
      YAM-5-I-SAD evidenced good internal consistency and construct validity.
      LIMITATIONS: Data are limited to the social anxiety subscale. CONCLUSIONS: The
      YAM-5-I-SAD is a sensitive and specific measure to screen for adolescents with
      social anxiety.

PMID- 29655077
TI  - Trends in depression among low-income mothers in the United States, 2005-2015.
AB  - BACKGROUND: Prior research has examined the association between low-income status
      and maternal depression; however, important questions remain in terms of trends
      in the prevalence of major depressive episodes (MDE) and treatment seeking among
      mothers in the United States. The objective of the present study is to examine
      trends in MDE among low-income mothers and explore perceived barriers to mental
      health treatment seeking. METHODS: Using data from the National Survey on Drug
      Use and Health (NSDUH; 2005-2015), we examined the prevalence of past-year MDE
      among mothers living in poverty (0-99% federal poverty line [FPL]; n = 23,264)
      and near-poverty (100-200% FPL; n = 21,655). Consistent with the Center for
      Disease Control and Prevention (CDC) guidelines, we conducted survey-adjusted
      logistic regression analyses to examine the significance of survey year in
      relation to MDE while controlling for key social demographic correlates. RESULTS:
      The overall decreasing MDE trend was found only among mothers in near-poverty,
      not mothers in poverty. Only for mothers in poverty, financial (AOR = 0.70, 95%
      CI = 0.52-0.95) and information barriers (AOR = 0.53, 95% CI = 0.39-0.73) were
      associated with mental health service use. LIMITATIONS: Self-reports of
      depressive symptoms and service receipt may have led to over or underreporting
      due to recall or social desirability bias. Additionally, NSDUH data are cross
      sectional and thereby limit our ability to make causal inferences. CONCLUSIONS:
      Greater attention should be paid to the prevention/treatment of depression among
      mothers in poverty. Efforts may include expanding financial assistance for mental
      health service use and educational campaigns to increase awareness of services
      available.

PMID- 29655078
TI  - Kynurenine pathway changes in late-life depression.
AB  - BACKGROUND: Kynurenine pathway (KP) activation is associated with several
      neuropsychiatric diseases, including major depression disorder (MDD). Although
      several investigations have been conducted on MDD, these have seldom shed light
      on KP changes in late-life depression (LLD). OBJECTIVE: We aimed to investigate
      whether tryptophan (TRP) metabolism and kynurenine (KYN) metabolism are
      imbalanced in LLD patients and to explore the differences in KP characteristics
      between early onset depression (EOD) and late onset depression (LOD) patients.
      METHODS: We investigated 170 LLD patients (EOD 90, LOD 80) and 135 normal
      controls. Serum concentrations of TRP, KYN and kynurenic acid (KYNA) were
      detected by the liquid chromatography-tandem mass spectrometry method. Depressive
      symptoms were assessed by the 17-item Hamilton Depression Scale (HAMD-17).
      RESULTS: LLD patients exhibited lower levels of TRP, KYN, KYNA and KYNA/KYN ratio
      and a higher level of KYN/TRY ratio than normal controls. The decrease in TRP and
      the increase in KYN/TRP ratio were found in LOD patients. A low TRP level without
      increased KYN/TRP ratio was found in EOD patients. The "Depression" factor, which
      was extracted from HAMD-17 by the principal component factor analysis, was
      correlated with the TRP level and KYNA/KYN ratio in the EOD group, but no such
      correlation was found in the LOD group. CONCLUSIONS: KP changes were observed in
      LLD patients; LOD patients showed profound shifts in TRP metabolism, while EOD
      patients showed low TRP level and a shift in KYN metabolism.

PMID- 29655079
TI  - Early maladaptive schemas in depression and somatization disorder.
AB  - Cognitive theories of depression posit that early maladaptive schemas (EMSs) are
      key vulnerability factors for psychological disorders. In this study, we
      investigated specific EMSs as shared or distinct cognitive vulnerability factors
      for depression and somatization disorder. The sample consisted of patients with
      Major depressive disorder (N = 30) and Somatization disorder (N = 30) from a
      community hospital or a psychiatric clinic. Participants completed the Structured
      Clinical Interview for DSM-IV (SCID), the Beck Depression Inventory-II (BDI-II),
      and the short form of the Young Schema Questionnaire (YSQ-SF). Depressed patients
      exhibited significantly higher levels of all five schema domains and specific
      maladaptive schemas, including emotional deprivation, mistrust and abuse, social
      isolation and alienation, defectiveness and shame, failure, subjugation,
      emotional inhibition, and insufficient self-control or self-discipline. Moreover,
      depressed patients exhibited significantly higher levels of social isolation,
      emotional inhibition, as well as the overvigilance and inhibition domain when
      depressive symptom severity was controlled. Our results provide preliminary
      evidence that specific EMSs distinguish patients with depression and
      somatization. Suggestions for future research include the need to have a non
      psychiatric control group, to evaluate the absolute role of EMSs in Somatization
      Disorder.

PMID- 29655080
TI  - The relationship between PTSD and suicidality among Wenchuan earthquake
      survivors: The role of PTG and social support.
AB  - BACKGROUND: Previous studies have found that suicide rates are likely to increase
      after the occurrence of earthquakes. Most existing studies that examined the
      relationship between PTSD and suicidality focus on risk factors. It remains
      unclear whether protective factors, such as post-traumatic growth (PTG) and
      social support, play a role in this relationship. OBJECTIVES: The aim of this
      study was to investigate the role of PTG and social support in the association
      between PTSD and suicidality, using data from a cross-sectional study conducted
      in China. METHODS: 1,369 participants were recruited from two study sites that
      were severely affected by the Wenchuan earthquake. Univariate and multivariate
      regression analyses were conducted to examine the relationship between PTSD, PTG,
      social support, and suicidality. RESULTS: The results indicate that the
      prevalence of suicidal ideation, suicide plans, and suicide attempts among adult
      survivors were 9.06%, 2.97% and 3.31%, respectively, even after 8 years following
      the Wenchuan earthquake. Furthermore, the findings show that PTSD was
      significantly associated with suicidality (OR = 1.96; 95% CI = 1.53, 2.52).
      Additionally, individuals reporting lower levels of social support and the
      acquisition of PTSD (OR = 5.99; 95% CI = 1.66, 21.56) were significantly related
      to suicidality. Moreover, compared to individuals who reported no presence of
      PTSD and high PTG, those who lived with PTSD and lower levels of PTG (OR = 2.33;
      95%CI = 1.00, 5.42) were more likely to report suicidality. LIMITATIONS: The
      cross-sectional design of this study limits our ability to determine causal
      relationships. Effects of other related factors, such as cultural and life
      events, were not examined in this study. CONCLUSIONS: Suicidality is a long-term
      health issue among survivors of the Wenchuan earthquake. PTG and social support
      play important roles on the association between PTSD and suicidality and are
      important contributing factors to understanding this relationship. These results
      contribute new knowledge of suicidal risk for a number of years after an
      earthquake and have implications for further mental health promotion following
      earthquakes.

PMID- 29655081
TI  - PI3K-AKT-GSK3beta-CREB signaling pathway regulates anxiety-like behavior in rats
      following alcohol withdrawal.
AB  - BACKGROUND: Alcohol abuse and anxiety disorders often occur concurrently, but
      their underlying cellular mechanisms remain unclear. Neuroadaptation within the
      medial prefrontal cortex (mPFC) have been implicated in the molecular mechanisms
      underlying alcohol drinking behavior and withdrawal. METHODS: A chronic alcohol
      exposure rat model (35 consecutive days of 10% alcohol intake and 48 h of
      withdrawal) was established, then, wortmannin (0.5 ug/side) was injected
      bilaterally into the mPFC. The elevated plus maze (EPM) and open field test (OFT)
      were used to assess anxiety-like behavior. Western blot assays were used to
      assess protein levels. RESULTS: We found that anxiety-like behavior peaked
      approximately 6 h after alcohol withdrawal. However, wortmannin greatly decreased
      alcohol intake and attenuated anxiety-like behavior in the alcohol exposure rats.
      Moreover, the PI3K-AKT-GSK3beta signaling pathway was activated after alcohol
      withdrawal, and phosphorylation of the downstream cAMP response element-binding
      protein (CREB) was increased. Wortmannin uniformly reversed PI3K-AKT-GSK3beta
      CREB pathway phosphorylation. LIMITATIONS: The downstream GSK3beta activity was
      not intervened and a single dose level of wortmannin was used. CONCLUSION: Our
      results suggest that activating the PI3K-AKT-GSK3beta-CREB pathway in the mPFC is
      an important contributor to the molecular mechanisms underlying alcohol
      withdrawal. PI3K signaling pathway inhibitors are thus potential candidates for
      treating alcohol abuse.

PMID- 29655082
TI  - Photoactivatable substrates for systematic study of the impact of an
      extracellular matrix ligand on appearance of leader cells in collective cell
      migration.
AB  - Epithelial cells migrate as multicellular units. The directionality and speed of
      these units are determined by actively moving leader cells. It is important to
      understand how external cues affect the appearance of these leader cells in
      physiological and pathological processes. However, the impact of extracellular
      matrices (ECMs) is still controversial, because physically-adsorbed ECM proteins
      are amenable to protein remodeling, and uncontrolled cluster geometry can vary
      migration phenotypes. Here, we demonstrate a photoactivatable substrate, which we
      used to study the impact of a cyclic Arg-Gly-Asp (cRGD) ligand on leader cell
      formation in MDCK cells. This robust platform allowed us to investigate the
      effect of cRGD density on leader cell formation, in any given cluster geometry,
      with minimized ECM remodeling. Our results show a biphasic response of leader
      cell appearance upon reducing the surface cRGD density. The increase, in leader
      cell appearance, within the higher density range, is not only associated with the
      weakening of circumferential actomyosin belts, but also reduction of cellular
      mechanical tension and intercellular junctional E-cadherin. These results
      indicate that cRGD-mediated cell-ECM interactions positively regulate mechanical
      and biochemical coupling within cell clusters; both are critical for the
      coordination of cell collectives and eventual reduction in the appearance of
      leader cells.

PMID- 29655083
TI  - Design, synthesis, anti-lung cancer activity, and chemosensitization of tumor
      selective MCACs based on ROS-mediated JNK pathway activation and NF-kappaB
      pathway inhibition.
AB  - EF24 and F35 both were effective monocarbonyl curcumin analogues (MCACs) with
      excellent anti-tumor activity, however, drug defect such as toxicity may limit
      their further development. To get anti-lung cancer drugs with high efficiency,
      low toxicity and chemosensitization, a series of analogues based on EF24 and F35
      were designed and synthesized. A number of compounds were found to exhibit
      cytotoxic activities selectively towards lung cancer cells compared to normal
      cells. Among these compounds, 5B was considered as an optimal anti-tumor agent
      for lung cancer cells with IC50 values ranging from 1.0 to 1.7 MUM, selectivity
      index (SI, as a logarithm of a ratio of IC50 value for normal and cancer cells)
      were all above 1.1, while the SI of EF24 and F35 were less than 0.8. Consistent
      with selectivity in vitro, 5B was observed to show lower toxicity in acute
      toxicity experiment than EF24 and F35 respectively. Further, 5B was found to
      exert anti-tumor effects through ROS-mediated activation of JNK pathway and
      inhibition of NF-kappaB pathway. 5B could significantly enhance the sensitivity
      of A549 cells to cisplatin or 5-Fu. These findings suggested that 5B was an
      effective and less toxic MCAC and provided a promising candidate for anti-tumor
      drugs.

PMID- 29655084
TI  - Discovery of novel Methylsulfonyl phenyl derivatives as potent human
      Cyclooxygenase-2 inhibitors with effective anticonvulsant action: Design,
      synthesis, in-silico, in-vitro and in-vivo evaluation.
AB  - A novel series of methylsulfonyl phenyl derivatives has been designed and
      synthesized to evaluate their COX-2 inhibitory activity along with anti
      convulsant potential. In-vitro evaluation revealed that two compounds MTL-1 and
      MTL-2 appeared as most potent and selective COX-2 inhibitors in the entire
      series. Anti-convulsant activity of both potent COX-2 inhibitors was assessed in
      sc-PTZ induced seizure test and MTL-1 excellently protected animals against PTZ
      induced seizure at the dose of 30 mg/kg. MTL-1 also indicates long duration of
      action in time course study and displayed significant seizure protection up to 6
      h of drug administration. Further, the anti-epileptogenic effect of MTL-1 has
      been examined in PTZ induced chronic model of epilepsy. The results indicated
      that MTL-1 had a significant anti-epileptogenic effect in PTZ kindled rats as
      compared to Etoricoxib (ETX) and PTZ alone treated group. Additionally, MTL-1
      successfully improved cognition deficit in PTZ kindled rats, which was confirmed
      by social recognition, novel object recognition and light-dark chamber tests.
      Moreover, molecular docking and molecular simulation (MD simulation) studies were
      also performed to elucidate the interaction of MTL-1 with the active site of COX
      2 and results showed that MTL-1 suitably binds within active site of COX-2. To
      investigate the safety profile of MTL-1, a sub-acute toxicity study was also
      performed and MTL-1 emerged as a new non-toxic chemical entity. Thus, the present
      investigation discovered a potent and safe COX-2 inhibitor, which is endowed with
      an effective anti-epileptic action.

PMID- 29655085
TI  - Adiposity at different periods of life and risk of adult glioma in a cohort of
      postmenopausal women.
AB  - BACKGROUND: Little is known about risk factors for adult glioma. Adiposity has
      received some attention as a possible risk factor. METHODS: We examined the
      association of body mass index (BMI), waist circumference (WC) and waist-to-hip
      ratio (WHR), measured at enrollment, as well as self-reported weight earlier in
      life, with risk of glioma in a large cohort of postmenopausal women. Over 18
      years of follow-up, 217 glioma cases were ascertained, including 164
      glioblastomas. Cox proportional hazards models were used to estimate hazard
      ratios and 95% confidence intervals. RESULTS: There was a modest, non-significant
      trend toward increasing risk of glioma and glioblastoma with increasing measured
      BMI and WHR. No trend was seen for WC. Self-reported BMI earlier in life showed
      no association with risk. CONCLUSIONS: Our weak findings regarding the
      association of adiposity measures with risk of glioma are in agreement the
      results of several large cohort studies. In view of the available evidence,
      adiposity is unlikely to represent an important risk factor for glioma.

PMID- 29655086
TI  - Childhood nephroblastoma in Southern and Eastern Europe and the US: Incidence
      variations and temporal trends by human development index.
AB  - BACKGROUND: Despite advances in the management of nephroblastoma (Wilms' tumor,
      WT), the etiology of the tumor remains obscure. We aimed to compare
      nephroblastoma incidence rates and time trends among children (0-14 years) in 12
      Southern and Eastern European (SEE) countries and the Surveillance, Epidemiology,
      and End Results Program (SEER), USA, in relation to the human development index
      (HDI). METHODS: In total 1776 WT cases were recorded in 13 SEE collaborating
      registries (circa 1990-2016), whereas data on 2260 cases (1990-2012) were
      extracted from the SEER database. Age-standardized incidence rates (AIRs) were
      calculated and correlated with HDI, whereas temporal trends were evaluated using
      Poisson regression and Joinpoint analyses. RESULTS: The overall SEE AIR (9.2/106)
      was marginally higher than that of the SEER (8.3/106), whereas significant
      differences were noted among the 13 SEE registries which comprised mainly
      Caucasian populations. A statistically significant temporal increase in incidence
      was noted only in Belarus. Most cases (~75%) were diagnosed before the fifth year
      of life, with rates steadily declining thereafter; median age at diagnosis was
      similar in SEE countries and SEER. A slight male preponderance in the first year
      of life (male:female = 1.1) was followed by a female preponderance in the older
      age groups (male:female = 0.7). Lastly, a statistically significant positive
      association between higher HDI and increasing nephroblastoma incidence was noted
      (regression coefficient: +3.25, 95%CI: +1.35, +5.15). CONCLUSIONS: Variations in
      incidence and time trends across the examined registries, changing male-to-female
      patterns with advancement in age, and positive associations with the HDI imply a
      plausible role for environmental and genetic factors in disease etiology, and
      these need to be explored further.

PMID- 29655087
TI  - Coach and player attitudes to injury in youth sport.
AB  - OBJECTIVES: To investigate coach and player attitudes to injury in New Zealand
      (NZ) secondary school sport. DESIGN: Cross-sectional survey SETTING: Secondary
      school sport. PARTICIPANTS: Secondary school coaches and players. MAIN OUTCOME
      MEASURES: Responses to a survey of injury attitudes. The survey was distributed
      in electronic and paper-based form to secondary school coaches and players across
      three sporting organisations. Coaches' uptake of injury prevention training and
      whether they had first aid qualifications was also elicited. RESULTS: 117 coaches
      and 226 players from netball, football and basketball participated. The majority
      of coaches surveyed (n = 82, 70%) reported having a coaching qualification and 72
      (62%) had completed a sport related first aid/injury prevention programme.
      Overall, 196 players (87%) reported hiding an injury to continue playing, and 102
      coaches (87%) and 205 players (91%) had witnessed injured players play on.
      Approximately 50% of players and coaches had seen players put under pressure to
      play when injured. A lack of knowledge, the desire to win, and not letting the
      team down were key reasons given for the behaviour reported. CONCLUSIONS: The
      observed prevalence of players playing on when injured and associated attitudes
      to secondary school sport injuries demands further investigation.

PMID- 29655088
TI  - The prevalence of generalized and syndromic hypermobility in elite Australian
      dancers.
AB  - OBJECTIVES: To determine the prevalence of Generalized Joint Hypermobility (GJH)
      and Joint Hypermobility Syndrome/Ehlers-Danlos Syndrome-Hypermobility Type
      (JHS/EDS-HT) among dancers using established validated measures. DESIGN:
      Observational Cohort Study. SETTING: Laboratory. PARTICIPANTS: 85 dancers from
      two dance institutions. MAIN OUTCOME MEASURES: GJH was determined using the
      Beighton score (cut-point >=5/9) and the Lower Limb Assessment Scale (LLAS) (cut
      point >=7/12). Presence of JHS/EDS-HT was assessed using the Brighton and
      Villefranche criteria. Paired sample t-test was performed to compare LLAS side-to
      side scores, and percentage disagreements calculated to determine differences
      between the two GJH and the two JHS/EDS-HT measures. RESULTS: 72% of dancers met
      the Beighton cut-point for GJH, while 38% and 42% met the LLAS cut-point on the
      left and right respectively. The proportion of dancers identified with GJH was
      different when assessed using the Beighton compared to the left and right LLAS
      (both p < 0.001), a disagreement of 48% and 46% respectively, with Beighton
      classifying more participants as having GJH. The Villefranche identified more
      dancers with JHS/EDS-HT than the Brighton (84% vs 31%, p < 0.001), with 54%
      disagreement. CONCLUSIONS: High prevalence of generalized and syndromic
      hypermobility was found regardless of the criteria used. A higher Beighton cut
      point, e.g. >=6/9, to identify true GJH amongst dancers maybe warranted.

PMID- 29655089
TI  - Hip kinematics during functional tasks in females with patellofemoral pain:
      Modification following rehabilitation and correlation with clinical improvement.
AB  - OBJECTIVES: To compare hip kinematics during two functional tasks in females with
      and without patellofemoral pain (PFP), and to determine if hip kinematics and,
      symptoms and functional limitations were improved after a rehabilitation program.
      DESIGN: Cross sectional and longitudinal. PARTICIPANTS: Sixteen females with and
      15 without PFP. SETTING: Laboratory and physical therapy clinic. MAIN OUTCOME
      MEASURES: Hip adduction (HADD) and medial rotation (HMR) peak angles, time
      integrals and inter-movement variability during step-down and vertical drop jump,
      symptoms and functional limitations evaluated using the Activities of Daily
      Living Scale of the Knee Outcome Survey (KOS-ADLS). RESULTS: At baseline, no
      significant differences were found in step-down and vertical drop jump between
      PFP and controls. Following rehabilitation, significant improvements were
      reported in KOS-ADLS (p < 0.001). There was a significant decrease in HADD and
      HMR variability (p < 0.05), a trend for decreased peak HMR (p = 0.06) during step
      down, and a significant decrease in HADD variability (p < 0.05) during vertical
      drop jump. These kinematic changes did not correlate with changes in KOS-ADLS
      (all p > 0.05). CONCLUSION: Females with and without PFP demonstrated no hip
      kinematic differences during functional tasks. A rehabilitation program improved
      symptoms and functional status, and modified hip kinematics in females with PFP;
      however these changes were not correlated.

PMID- 29655090
TI  - Metataxonomy and functionality of wood-tar degrading microbial consortia.
AB  - Wood-tar is a liquid material obtained by wood gasification process, and
      comprises several polycyclic aromatic hydrocarbons (PAH). Tar biodegradation is a
      very challenging task, due to its toxicity and to its complex chemistry. The
      'microbial resource management' concerns the use of environmental microbial
      communities potentially able to provide us services. We applied this concept in
      tar biodegradation. Tar composed by several PAH (including phenanthrene,
      acenaphthylene and fluorene) was subjected to a biodegradation process in
      triplicate microcosms spiked with a microbial community collected from PAH-rich
      soils. In 20 days, 98.9% of tar was mineralized or adsorbed to floccules, while
      negative controls showed poor PAH reduction. The dynamics of fungal and bacterial
      communities was assessed through Automated Ribosomal Intergenic Spacer Analysis
      (ARISA), 454 pyrosequencing of the fungal ITS and of the bacterial 16S rRNA.
      Quantification of the degrading bacterial communities was performed via
      quantitative Real Time PCR of the 16S rRNA genes and of the cathecol 2,3
      dioxygenase genes. Results showed the importance of fungal tar-degrading
      populations in the first period of incubation, followed by a complex bacterial
      dynamical growth ruled by co-feeding behaviors.

PMID- 29655091
TI  - Effects of different oxyanions in solution on the precipitation of jarosite at
      room temperature.
AB  - The effects of five different oxyanions, AsO4, SeO3, SeO4, MoO4, and CrO4, on the
      precipitation of jarosite at room temperature were investigated by X-ray
      diffraction, scanning electron microscopy, and chemical analysis. Different
      amounts (2, 5, and 10 mol%) of oxyanions in the starting solution and different
      aging times (1 h-40 days) were used for the experiment. In the initial stage,
      only the amorphous phase appears for all samples. With increasing aging time,
      jarosite and jarosite with oxyanions start precipitating at room temperature with
      different precipitation rates and crystallinities. Jarosite with AsO4 shows the
      lowest precipitation rate and lowest crystallinity. With increasing amounts of
      oxyanions, the crystallization rate decreases, especially for jarosite with AsO4.
      The jarosite samples with CrO4 and SeO4 show the fastest precipitation and
      highest crystallinities. For the jarosite samples with a low precipitation rate
      and low crystallinity, the amorphous phase contains high concentrations of
      oxyanions, probably because of the fast precipitation of the amorphous iron
      oxyanion phase; however, the phase with fast jarosite precipitation contains
      fewer oxyanions. The results show that coprecipitation of jarosite can play a
      more important role in controlling the behavior of CrO4 than AsO4 in acid mine
      drainage.

PMID- 29655092
TI  - Why, who and when to start treatment for chronic hepatitis B infection.
AB  - Chronic hepatitis B remains a major global health challenge due to morbidity and
      mortality from hepatocellular carcinoma and complications of liver cirrhosis.
      Current treatment regimens are non-curative and, once initiated, treatment is of
      indefinite duration for the majority. The decision to initiate treatment
      decisions is based on risk stratification. Advances in our understanding of the
      natural history of chronic hepatitis B have led to a paradigm shift in
      recommendations for treatment. Emerging non-invasive biomarkers of disease
      activity will further enhance disease stratification. In this review, we
      summarise the guidance from major international societies on treatment for
      chronic hepatitis B and explore some of the novel approaches to disease
      assessment.

PMID- 29655093
TI  - A combination of representative compounds, metabolism platform and diagnostic
      extraction strategy for characterization of metabolites of Shuang-Huang-Lian oral
      liquid in vivo by ultra-performance liquid chromatography coupled with time-of
      flight mass spectrometry.
AB  - Traditional Chinese medicines (TCMs) usually contained a large number of chemical
      components, which could be transformed into more complex metabolites in vivo. In
      this work, a "Representative compounds-Metabolism platform-Diagnostic extraction"
      strategy (RMD strategy) was proposed for comprehensively identification or
      characterization of xenobiotics in rat after oral administration of TCMs. Shuang
      Huang-Lian oral liquid (SHL), a well-known traditional Chinese medicine
      preparation, was used as an example. The metabolic pathways of six representative
      compounds, bearing five different core structures in SHL, were elucidated and
      their metabolic reactions were employed for exploring metabolites of homologous
      components in metabolism platform. Meanwhile, diagnostic ions extraction were
      also used for screening more structural analogues in biofluids. All this work was
      completed by ultra-performance liquid chromatography coupled electrospray
      ionization quadruple time-of-flight mass spectrometry (UPLC/Qtof MS) and UNIFI
      metabolism platform. As a result, a total of 254 xenobiotics were identified or
      tentatively characterized in rat plasma and urine after oral administration of
      SHL and six representative compounds. The metabolism reaction included phase I
      reaction (hydroxylation, hydrolysis reaction, deglycosylation, hydrogenation,
      demethylation, dehydroxylation and ring opening reaction) and phase II reaction
      (glucuronidation, sulfation and methylation). This research provided useful
      information for further study of the pharmacology and mechanism of SHL in vivo.
      It also demonstrated that RMD strategy was an efficient approach for facilitate
      screening-out and rapid identification of xenobiotics in biological samples after
      oral administration of TCMs.

PMID- 29655094
TI  - Semi-quantitative measurement of the antimalarial lumefantrine from untreated
      dried blood spots using LC-MS/MS.
AB  - Study of the clinical effects of combination therapy for malaria is aided by the
      ability to measure concentrations of individual partner drugs. Existing methods
      for measurement of the antimalarial drug lumefantrine (LF) in dried blood spots
      (DBS) on filter paper rely on chemical pretreatment of the paper to facilitate
      drug elution. However, in the absence of pretreatment, DBS may still offer some
      utility for semi-quantitative measurements and pharmacokinetic-pharmacodynamic
      (PK-PD) analyses. We present a method for semi-quantitation of LF in DBS on
      untreated filter paper using liquid chromatography tandem mass spectrometry.
      Optimal recovery was achieved by extraction with acetone-water-formic acid
      (90:5:5). The range of quantitation was 100-20,000ng/ml. Mean intra- and inter
      day accuracy values were 86.6% (coefficient of variation [CV]: 10.1%) and 91.8%
      (CV: 16.1%), therefore we propose the assay as semi-quantitative. Clinical
      application was demonstrated in exploratory PK-PD analyses of a drug efficacy
      trial of artemether-lumefantrine in children with uncomplicated falciparum
      malaria using post-treatment day 7 samples, parasite clearance times estimated
      from serial blood smears, and recurrence of malaria out to 35days. The median day
      7 concentration among children (n=71) was 111ng/ml (interquartile range: 100
      194ng/ml). We used a truncated calibration curve of 100-5000ng/ml for
      calculations due to low observed concentrations. Calculations using the full
      calibration curve yielded similar values (+1% avg. deviation). Controlling for
      participant age, sex, and parasite burden, each log increase in LF day 7
      concentration corresponded to a decrease of 7.1h in mean parasite clearance time
      (95% confidence interval: 0.1-14.3h, P=0.05). A nested case-control study of
      participants (n=18) with and without recurrent malaria showed mean post-treatment
      day 7 concentrations of 181ng/ml and 235ng/ml, respectively, but the difference
      was not significant (P=0.64). A method for semi-quantitation of LF from post
      treatment day 7 collections of DBS on untreated filter paper demonstrated
      clinical application in exploratory PK-PD analyses of parasite clearance and
      reinfection. Use of DBS will endure in certain study settings by virtue of their
      ease of collection and resilience. Their utility should continue to be explored
      as our instruments gain in sensitivity and as clinical pharmacology inquiries are
      pursued to the field.

PMID- 29655095
TI  - Sub-chronic inhalation of reclaimed water-induced fibrotic lesion in a mouse
      model.
AB  - When reclaimed water is used as municipal miscellaneous water, acute exposure of
      the generated aerosol with high levels of endotoxins can cause severe
      inflammation in the lungs. However, the potential risks of long-term inhalation
      of reclaimed water remains unclear. To identify the adverse effects of sub
      chronic reclaimed water inhalation and explain the underlying mechanisms, a mouse
      model of 12-week sub-chronic exposure was established, and wastewater before a
      membrane bioreactor (MBR, positive control) and the MBR effluent (reclaimed
      water, which met the quality standard of urban use and was currently used for
      landscape irrigation) were tested in this study. The exposure dose was set to
      approach the real working scenarios. Lung lavage and histology were analyzed.
      Obvious epithelial cell apoptosis in the bronchi was observed, along with the
      accumulation of myofibroblasts and the collagen deposition both in main bronchi
      and terminal bronchioles. All these symptoms were persistent after 4 weeks of
      recovery. Inflammation and induced bronchus-associated lymphoid tissues (iBALT)
      were also observed but diminished after recovery indicating inflammation may not
      be the direct cause of the symptom. Furthermore, two fibrogenic cytokines (TNF
      alpha and TGF-beta) were constantly high in the lung during the study. They might
      be the biomarkers of lung damage after the inhalation of reclaimed water.
      Adaptive immune responses were also detected as elevated levels of IgG and IgA,
      but not for IgE. Inhalation of reclaimed water causes sustained fibrotic lesions
      in the lungs, which suggests potential health risks during urban application
      where aerosols generated.

PMID- 29655096
TI  - Precipitation thresholds for fecal bacterial indicators in the Chesapeake Bay.
AB  - Many coastal states of the United States restrict harvest of shellfish from
      select areas based on some environmental trigger. Such areas are classified as
      being conditionally approved. In Maryland, the trigger is an inch or more of
      rainfall that has fallen in the last 24 h. This study used 11 years of monitoring
      data to test the relationship between daily rainfall totals and densities of
      fecal indicators in Maryland shellfish harvest waters. Precipitation and fecal
      coliform (FC) water monitoring data from 2004 to 2014 were matched by date and
      watershed. The influence of antecedent rainfall conditions (i.e. rainfall in the
      preceding days or weeks) and the distance of each monitoring station to land were
      compared to the percent of samples exceeding the FDA criterion for managing
      shellfish harvest areas. Sample stations beyond 1000m from land had FC densities
      consistently below the FDA criterion and were excluded from further analysis.
      Rainfall events greater than an inch tended to result in significantly elevated
      FC for the following two days, followed by lower levels thereafter. The total
      amount of rain in the last three weeks was positively related to the proportion
      of samples with FC greater than the FDA criterion. Bay-wide, the percent of
      samples exceeding the FDA criterion rose from seven percent for rainfall less
      than an inch to 37% following one or more inches of rain. Watersheds were
      classified based on the percent of FC densities over the criterion when rainfall
      was an inch or more, with 41 of 81 watersheds showing FC responses indicative of
      potential conditionally approved areas, those shellfish growing areas where the
      one inch precipitation trigger may be applied. These areas largely overlapped the
      current conditionally approved areas defined by Maryland. The percent of open
      water, wetlands, and poorly drained soils explained a significant amount of the
      variability (R2 = 0.72) in the difference in percent of samples exceeding the FDA
      criterion when rainfall was greater than an inch and when it was less than an
      inch. Logistic regression analysis showed that the current trigger of one inch of
      rain in 24 h is predictive of FC densities over the FDA criterion, though the
      appropriate threshold will most likely depend on how far the particular shellfish
      growing area is from land and antecedent rain conditions. In watersheds with
      relatively high percentages of open water to total watershed size, higher
      rainfall thresholds might be appropriate. The approach taken in this study could
      be applied to individual stations and sub-watersheds, potentially allowing the
      reclassification of some shellfish harvest areas.

PMID- 29655097
TI  - A method for the statistical interpretation of friction ridge skin impression
      evidence: Method development and validation.
AB  - The forensic fingerprint community has faced increasing amounts of criticism by
      scientific and legal commentators, challenging the validity and reliability of
      fingerprint evidence due to the lack of an empirically demonstrable basis to
      evaluate and report the strength of the evidence in a given case. This paper
      presents a method, developed as a stand-alone software application, FRStat, which
      provides a statistical assessment of the strength of fingerprint evidence. The
      performance was evaluated using a variety of mated and non-mated datasets. The
      results show strong performance characteristics, often with values supporting
      specificity rates greater than 99%. This method provides fingerprint experts the
      capability to demonstrate the validity and reliability of fingerprint evidence in
      a given case and report the findings in a more transparent and standardized
      fashion with clearly defined criteria for conclusions and known error rate
      information thereby responding to concerns raised by the scientific and legal
      communities.

PMID- 29655098
TI  - Three-dimensionally derived interlandmark distances for sex estimation in intact
      and fragmentary crania.
AB  - The skull is the element most frequently presented to forensic anthropologists
      for analysis yet weathering, corpse maiming, and scavenger activity often result
      in damage and fragmentation. This fragmentation results in a reduction in the
      number of traditional calliper derived measurements that can be obtained and
      subjected to discriminant based analyses for sex estimation. In this
      investigation, we employed three-dimensional geometric morphometric methods to
      derive novel interlandmark distance measures across six regions of the cranium
      including the basicranium, basipalate, zygoma, orbits and the cranium globally to
      create functions to discriminate sex with high efficacy, even in the event of
      fragmentation. Forty-five homologous landmarks were digitised across each of 227
      (114 males and 113 females) South African crania of European descent (white)
      sampled from the Raymond A Dart Collection of Human Skeletons, housed in the
      School of Anatomical Sciences, University of the Witwatersrand, South Africa. A
      total of 990 interlandmark distances (ILDs) were mathematically derived using
      Pythagorean geometry. These ILDs were then filtered by region and subjected to
      both direct and stepwise discriminant function analyses. Discriminant equations
      where derived for each region and achieved the following average cross-validated
      sex estimation accuracies: basicranium-74%; basipalate-80.2%; zygomatic-82.4;
      orbits-71.8%; nasomaxilla-83.7%; global cranium-88.2%. A large number of the ILDs
      used to derive the discriminant functions are novel, demonstrating the efficacy
      of geometric morphometric methods and illustrating the need to reassess old
      methods of data collection using modern methods to determine whether they best
      capture biological differences. The results of this study provide an invaluable
      contribution to forensic anthropology in South Africa as it provides an accurate,
      practical means of assessing sex using fragmentary material that may otherwise
      have been disregarded. These will undeniable aid in accurate sex estimation and
      ultimately, victim identification.

PMID- 29655099
TI  - Detection of latent fingerprint hidden beneath adhesive tape by optical coherence
      tomography.
AB  - Adhesive tape is one type of common item which can be encountered in criminal
      cases involving rape, murder, kidnapping and explosives. It is often the case
      that a suspect deposits latent fingerprints on the sticky side of adhesive tape
      material when tying up victims, manufacturing improvised explosive devices or
      packaging illegal goods. However, the adhesive tapes found at crime scenes are
      usually stuck together or attached to a certain substrate, and thus the latent
      fingerprints may be hidden beneath the tapes. Current methods to detect latent
      fingerprint hidden beneath adhesive tape need to peel it off first and then apply
      physical or chemical methods to develop the fingerprint, which undergo
      complicated procedures and would affect the original condition of latent print.
      Optical coherence tomography (OCT) is a novel applied techniques in forensics
      which enables obtaining cross-sectional structure with the advantages of non
      invasive, in-situ, high resolution and high speed. In this paper, a custom-built
      spectral-domain OCT (SD-OCT) system with a hand-held probe was employed to detect
      fingerprints hidden beneath different types of adhesive tapes. Three-dimensional
      (3D) OCT reconstructions were performed and the en face images were presented to
      reveal the hidden fingerprints. The results demonstrate that OCT is a promising
      tool for rapidly detecting and recovering high quality image of latent
      fingerprint hidden beneath adhesive tape without any changes to the original
      state and preserve the integrity of the evidence.

PMID- 29655100
TI  - Evaluation of 1,5-anhydro-d-glucitol in clinical and forensic urine samples.
AB  - Because of the lack of characteristic morphological findings post mortem
      diagnosis of diabetes mellitus and identification of diabetic coma can be
      complicated. 1,5-Anhydroglucitol (1,5-AG), the 1-deoxy form of glucose, competes
      with glucose for renal reabsorption. Therefore low serum concentrations of 1,5
      AG, reflect hyperglycemic excursions over the prior 1-2 weeks in diabetic
      patients. Next to clinical applications determination of 1,5-AG can also be used
      in forensic analysis. To investigate the elimination of 1,5-AG, a liquid
      chromatographic-mass spectrometric method for the determination of 1,5-AG and
      creatinine in urine was developed and validated according to international
      guidelines. To evaluate ante mortem concentrations of 1,5-AG spot urine samples
      of 30 healthy subjects, 46 type 1 and 46 type 2 diabetic patients were analyzed.
      1,5-AG urine concentrations of diabetic patients were significantly (p<0.001)
      lower (mean: 1.54MUg/ml, n=92) compared to concentrations of healthy subjects
      (mean: 4.76MUg/ml, n=30) which led to the idea that 1,5-AG urine concentrations
      post mortem might help in the interpretation of a diabetic coma post mortem.
      Urine of 47 deceased non-diabetics, 37 deceased diabetic and 9 cases of diabetic
      coma were measured. Comparison of blood and urine 1,5-AG concentrations in clinic
      samples (linear, R2=0.13) and forensic samples (linear, R2=0.02) showed no
      correlation. Urinary levels of 1,5-AG in deceased diabetic (mean 6.9MUg/ml) and
      in non-diabetic patients (mean 6.3MUg/ml) did not show a significant difference
      (p=0.752). However, urinary 1,5-AG concentrations in deceased due to diabetic
      coma (mean: 1.7MUg/ml) were significantly lower than in non-diabetic (mean:
      6.3MUg/ml, p=0.039) and lower than in diabetic cases (mean: 4.7MUg/ml, p=0.058).
      The determination of a reliable cut-off for the differentiation of diabetic to
      diabetic coma cases was not possible. Normalization of urinary 1,5-AG
      concentrations with the respective creatinine concentrations did not show any
      gain of information. In clinical (serum) and forensic blood samples a significant
      difference between all groups could be detected (p<0.05). Comparison of blood and
      urine 1,5-AG concentrations in clinical samples (linear, R2=0.13) and forensic
      samples (linear, R2=0.02) showed no correlation.

PMID- 29655102
TI  - Sonochemical degradation of endocrine-disrupting organochlorine pesticide
      Dicofol: Investigations on the transformation pathways of dechlorination and the
      influencing operating parameters.
AB  - Dicofol, an extensively used organochlorine pesticide and a recommended Stockholm
      convention persistent organic pollutant (POP) candidate is well known for its
      endocrine disruptive properties. The sonochemical degradation of Dicofol in
      aqueous media has been investigated using a 20-kHz probe type sonicator with
      power inputs from 150 to 450 W. The degradation rate was determined as a function
      of concentration of Dicofol, solution pH, bulk phase temperature, ultrasonic
      power density and H2O2 addition. At optimum operating conditions, the pseudo
      first-order degradation rate constant (k) was determined to be 0.032 min-1 and
      the extent of degradation was found to be 86% within 60 min of ultrasound
      treatment. High performance liquid chromatography (HPLC) and Gas chromatography
      coupled with mass spectroscopy (GC-MS) analysis indicated the presence of
      degraded products. The obtained results of Dicofol degradation and control
      experiments in the presence of H2O2 and radical scavenger test suggest thermal
      decomposition along with radical attack at bubble-vapor interface to be the
      dominant degradation pathway. Sonochemical treatment is effective and promising
      for successful removal of harmful pesticides such as Dicofol and superior removal
      efficiency for other POPs is expected in the near future with the successful
      implementation of ultrasound-based wastewater treatment.

PMID- 29655101
TI  - Hepatitis C virus status awareness and test results confirmation among people who
      inject drugs in Ukraine.
AB  - BACKGROUND: Among the estimated 340,000 people who inject drugs (PWID) in
      Ukraine, HCV prevalence is approximately 70%. As HCV treatment availability
      increases, an assessment of the HCV treatment cascade is needed to guide HCV
      prevention and treatment strategies. METHODS: Opioid dependent PWID were
      interviewed and tested for HIV and HCV in five Ukrainian cities from January 2014
      to March 2015. Logistic regression was used to examine the independent correlates
      of two cascade steps: a) anti-HCV positive status awareness; b) chronic HCV
      confirmation; and of c) annual HCV testing for PWID. RESULTS: Among 1613 PWID,
      1002 (62.1%) had anti-HCV positive test result, of which 568 (56.7%) were aware
      of it before the study and 346 (34.5%) reported previous confirmatory testing for
      chronic HCV. Independent correlates of being aware they had anti-HCV positivity
      included: current [AOR: 3.08; 95%CI: 2.16-4.40] or prior [AOR: 1.85; 95%CI: 1.27
      2.68] opioid agonistic treatment (OAT) experience, relative to no prior OAT,
      living in Lviv [AOR: 0.50; 95%CI: 0.31-0.81] or Odesa [AOR: 2.73; 95%CI: 1.51
      4.93] relative to Kyiv and being aware of having HIV [AOR: 4.10; 95%CI: 2.99
      5.62]. Independent correlates of confirming HCV infection among those who were
      aware of their anti-HCV positive status included: current OAT [AOR: 2.00; 95%CI:
      1.24-3.23], relative to prior OAT, the middle income category [AOR: 1.74, 95%CI:
      1.15-2.63], relative to the lowest, and receiving ART [AOR: 4.54; 95%CI: 2.85
      7.23]. Among 1613 PWID, 918 (56.9%) were either HCV negative or not aware of
      their HCV positive status, of which 198 (21.6%) reported recent anti-HCV test
      (during last 12 month). Recent anti-HCV test in this group was associated with
      current [AOR: 7.17; 95%CI: 4.63-11.13] or prior [AOR: 2.24; 95%CI: 1.32-3.81] OAT
      experience, relative to no prior OAT. CONCLUSION: Encouraging PWID to participate
      in OAT may be an effective strategy to diagnose and link PWID who are HCV
      positive to care. Among HIV negative participants, regular HCV testing may be
      ensured by participation in OAT. More studies are needed to assess HCV treatment
      utilization among PWID in Ukraine and OAT as a possible way to retain them in
      treatment.

PMID- 29655103
TI  - Evaluation of the early developmental neural toxicity of F-53B, as compared to
      PFOS, with an in vitro mouse stem cell differentiation model.
AB  - F-53B, as an alternative to the persistent organic pollutant perfluorooctane
      sulfonate (PFOS), is amply used in the electric plating industry. F-53B and PFOS
      have similar physicochemical, biochemical and physiological properties, due to
      the similarity in their chemical structure. Thus, they may also possess similar
      toxicities. Although epidemiological studies and in vivo assays have shown that
      prenatal exposure to PFOS may impair the development of the nervous system,
      toxicity data for F-53B are still scarce. In this study, we employed an embryonic
      stem cell (ESC) in vitro differentiation system, to detect the potential
      developmental neural toxicity of F-53B and PFOS, at human exposure relevant
      doses. We demonstrated that during early mouse ESC (mESC) neural differentiation,
      F-53B and PFOS disrupted the expression of neural marker genes and affected the
      morphology of the differentiated cells. However, the very same treatments did not
      cause any cytotoxic effects. In conclusion, our ESC in vitro differentiation
      system was able to prove for the first time that F-53B and PFOS at human exposure
      relevant concentrations, could alter the expression of differentiation
      biomarkers, indicating a potential developmental neural toxicity. Based on our
      findings, it is reasonable to deduce that excessive exposure to F-53B and PFOS
      may cause severe dysfunctions during early stages of embryo development.

PMID- 29655104
TI  - Nitrifying trickling filters and denitrifying bioreactors for nitrogen management
      of high-strength anaerobic digestion effluent.
AB  - The treatment of high-strength anaerobic digester effluent in laboratory-scale
      trickling filters for nitrification and then anaerobic filters for
      denitrification is reported. Five media types were investigated in the trickling
      filters: biochar, granular activated carbon (GAC), zeolite, Pall rings, and
      gravel. Three media were tested in five denitrifying filters: sand (S), bamboo
      wood chips (B), eucalyptus wood chips (E), bamboo with sand (B+S), and eucalyptus
      with sand (E+S). The different wood chips served as a supplemental electron donor
      for denitrification. From six months of operation, biochar, GAC, zeolite, Pall
      rings, and gravel media had turbidity (NTU) removal efficiencies of 90, 91, 77,
      74, and 74%, respectively, and ammonia removal efficiencies of 83, 87, 85, 30,
      and 80%, respectively, which was primarily by nitrification to nitrate. For the
      anaerobic filters, S, B, B+S, E, and E+S had nitrate removal efficiencies of 30,
      66, 53, 35, and 35%, and turbidity removal efficiencies of 88, 89, 84, 89, and
      88%, respectively. Biochar and bamboo were selected as the best combination of
      media for trickling filter and anaerobic filter sequential treatment. Based on an
      average initial influent of 600 mg NH3-N L-1, 50 mg NO3-N L-1, and 980 NTU, the
      biochar filter's effluent would be 97 mg NH3-N L-1, 475 mg NO3-N L-1, and 120
      NTU. The bamboo filter's final effluent would be 82 mg NH3-N L-1, 157 mg NO3-N L
      1, and 13 NTU, which corresponds to 63% removal of total N and 99% removal of
      turbidity. These filter media thus present a simple option for sustainable post
      treatment for nitrogen management and effluent polishing in low-resources
      settings.

PMID- 29655105
TI  - Effectiveness and potential risk of CaO application in Cd-contaminated paddy
      soil.
AB  - In this study, the accurate effectiveness of CaO in mitigating Cd bioavailability
      in paddy soil-rice system was investigated and moreover, the potential for
      reversibility of CaO liming process was provided. Increasing soil pH to >=6.5 by
      CaO was determined to be the minimal threshold for minimizing Cd transfer into
      rice in historically contaminated soils across light to severe Cd levels, while
      an elevated CaO ratio was needed for soil with recent input of Cd. In CaO
      remediation treatment, a reduced pool of bioavailable Cd in rhizosphere soil
      coupled with an increased Cd retention by Fe plaque and an inhibited planta Cd
      transfer was determined consistently and proposed to be largely responsible for
      the significant reduction in brown rice Cd. Under continuous simulated acid
      precipitation test, a negligible level of Cd in eluate with ~1 unit higher pH
      than control was recorded with CaO. Significant acidification, however, increased
      Cd solubilization in the limed soil than in unlimited control, notably at pH 5.5
      6.5. As indicated by Visual MINTEQ, a higher Cd-carbonate solubility and much
      decreased Cd complexation on Fe-(hydr)-oxides across this pH range occurred as a
      result of elevated Ca input. This suggests that a high soil pH (>=6.5) needs to
      be permanently maintained once liming has been performed to minimize Cd
      mobilization. Therefore, amending Cd-contaminated soils with CaO is a cost
      effective remedial measure for reducing Cd bioavailability to paddy rice, while a
      high soil pH need to be permanently maintained to sustain this beneficial effect.

PMID- 29655106
TI  - Combining emission inventory and isotope ratio analyses for quantitative source
      apportionment of heavy metals in agricultural soil.
AB  - Two quantitative methods (emission inventory and isotope ratio analysis) were
      combined to apportion source contributions of heavy metals entering agricultural
      soils in the Lihe River watershed (Taihu region, east China). Source
      apportionment based on the emission inventory method indicated that for Cd, Cr,
      Cu, Pb, and Zn, the mean percentage input from atmospheric deposition was highest
      (62-85%), followed by irrigation (12-27%) and fertilization (1-14%). Thus, the
      heavy metals were derived mainly from industrial activities and traffic
      emissions. For Ni the combined percentage input from irrigation and fertilization
      was approximately 20% higher than that from atmospheric deposition, indicating
      that Ni was mainly derived from agricultural activities. Based on isotope ratio
      analysis, atmospheric deposition accounted for 57-93% of Pb entering soil, with
      the mean value of 69.3%, which indicates that this was the major source of Pb
      entering soil in the study area. The mean contributions of irrigation and
      fertilization to Pb pollution of soil ranged from 0% to 10%, indicating that they
      played only a marginally important role. Overall, the results obtained using the
      two methods were similar. This study provides a reliable approach for source
      apportionment of heavy metals entering agricultural soils in the study area, and
      clearly have potential application for future studies in other regions.

PMID- 29655107
TI  - Effect of nitrate, carbonate/bicarbonate, humic acid, and H2O2 on the kinetics
      and degradation mechanism of Bisphenol-A during UV photolysis.
AB  - In this study, the effects of natural water components (nitrate,
      carbonate/bicarbonate, and humic acid) on the kinetics and degradation mechanisms
      of bisphenol A (BPA) during UV-C photolysis and UV/H2O2 reaction were examined.
      The presence of NO3- (0.04-0.4 mM) and CO32-/HCO3- (0.4-4 mM) ions increased BPA
      degradation during UV photolysis. Humic acid less than 3 mg/L promoted BPA
      degradation, but greater than 3 mg/L of humic acid inhibited BPA degradation.
      During the UV/H2O2 reaction, all water matrix components acted as radical
      scavengers in the order of humic acid > CO32-/HCO3- > NO3-. All of the
      degradation reactions agreed with the pseudo-first-order kinetics. While eight
      byproducts (m/z = 122, 136, 139, 164, 181, 244, 273, 289) were identified in UV
      C/NO3- photolysis reaction, four (m/z = 122, 136, 164, 244) and three byproducts
      (m/z = 122, 136, 164) were observed during UV-C/NO3-/CO32-/HCO3- and UV-C/CO32
      /HCO3- reactions. Nitrogenated and hydrogenated byproducts were first observed
      during the UV-C/NO3- photolysis, but only hydrogenated byproducts as adducts were
      detected during the UV-C/NO3-/CO32-/HCO3- photolysis. Nitrogenated and
      hydrogenated byproducts were formed in the early stage of degradation by OH or
      NO2 radicals, and these byproducts were subsequently degraded into smaller
      compounds with further reaction during UV-C/NO3- and UV-C/NO3-/CO32-/HCO3-
      reactions. In contrast, BPA was directly degraded into smaller compounds by beta
      scission of the isopropyl group by CO3-/HCO3 radicals during UV-C/CO32-/HCO3-
      reaction. Our results imply that the water components can change the degradation
      mechanism of BPA during UV photolysis.

PMID- 29655108
TI  - Chronic toxicity and endocrine disruption of naproxen in freshwater waterfleas
      and fish, and steroidogenic alteration using H295R cell assay.
AB  - Naproxen is a non-steroidal anti-inflammatory drug (NSAID) and has been
      frequently detected in surface waters around the world. Although endocrine
      disruption and reproduction related effects of NSAIDs are of increasing concern,
      the ecotoxicity of naproxen in aquatic organisms is limited primarily to acute
      lethal effects. In this study, chronic toxicity of naproxen was evaluated
      employing two daphnids (Daphnia magna and Moina macrocopa) and a fish (Oryzias
      latipes). The effects of naproxen on sex steroid hormones and gene transcription
      related to steroidogenesis were also evaluated in H295R cells. The chronic no
      observed effect concentrations (NOECs) of naproxen for reproduction were
      determined to be 10 mg L-1 in D. magna and 0.3 mg L-1 in M. macrocopa. At
      concentrations of 0.5 mg L-1, the survival of juvenile medaka fish was
      significantly decreased and transcription of erbeta2 gene was significantly
      increased. Concentration of 17beta-estradiol (E2) and the ratio of E2 and
      testosterone were significantly increased in H295R cells at 10 mg L-1, suggesting
      that naproxen could modulate sex hormone production. The current detected levels
      of naproxen in ambient Korean rivers are far lower than the effective levels,
      however potential adverse effects cannot be ignored in some highly polluted
      areas. Endocrine disruption effects in fish warrant further investigation
      particularly for their ecological implications.

PMID- 29655109
TI  - Indirect electrochemical oxidation of 2,4-dichlorophenoxyacetic acid using
      electrochemically-generated persulfate.
AB  - This research investigated persulfate electrosynthesis using a boron-doped
      diamond anode and a chemical reaction of persulfate in its activated form with an
      herbicide, 2,4-Dichlorophenoxyacetic acid (2,4-D). The first part of this
      research is dedicated to the influence of the applied current density on the
      electrosynthesis of persulfate. The first part shows that for a 2 M sulfuric
      acid, the current efficiency reached 96% for 5 mA/cm2 and dropped to 52% for a
      higher current density (100 mA cm-2). This fall cannot be explained by mass
      transfer limitations: an increase in temperature (from 9 to 30  degrees C) during
      electrolysis leads to the decomposition of 23% of the persulfate. The second part
      of this research shows that a quasi-complete degradation of the target herbicide
      can be reached under controlled operating conditions: (i) a high ratio of initial
      concentrations [Persulfate]/[2,4-D], (ii) a minimum temperature of 60  degrees C
      that produces sulfate radicals by heat decomposition of persulfate, and (iii) a
      sufficient contact time between reactants is required under dynamic conditions.

PMID- 29655110
TI  - Monitoring and mass balance analysis of endocrine disrupting compounds and their
      transformation products in an anaerobic-anoxic-oxic wastewater treatment system
      in Xiamen, China.
AB  - We investigated the occurrence, removal and mass balance of 8 endocrine
      disrupting compounds (EDCs), including estrone (E1), estradiol (E2), estriol
      (E3), ethinylestradiol (EE2), triclosan (TCS), triclocarbon (TCC), 4-n-nonyl
      phenol (NP) and 4-n-octyl phenol (OP), along with 5 of their transformation
      products (TPs), including 4-hydroxy estrone (4-OH E1), 4-hydroxy estradiol (4-OH
      E2), methyl triclosan (MeTCS), carbanilide (NCC), dichlorocarbanilide (DCC) in a
      wastewater treatment plant. Generally, E3 showed the highest concentrations in
      wastewater with median value of 514 ng/L in influent, while TCS and TCC showed
      highest level in sludge and suspended solids (SS) with median value of 960 and
      724 MUg/kg, respectively. Spatial variations were observed along each unit of the
      wastewater treatment processes for dissolved analytes in wastewater and adsorbed
      analytes in suspended solids and sludge. Special emphasis was placed to
      understand the mass load of EDCs and their TPs to the wastewater treatment unit
      and mass loss during the wastewater treatment processes. Mass loss based on both
      aqueous and suspended phase concentration revealed that majority of these
      chemicals were significantly removed during the treatment process except for TCS,
      TCC, and three of their TPs (MeTCS, NCC, DCC), which were released or generated
      during the treatment process. Mass load results showed that 42.4 g of these EDCs
      and their TPs entered this wastewater treatment system daily via influent,
      whereas 6.15 g and 7.60 g were discharged through effluent and sludge.

PMID- 29655111
TI  - Degradation of bisphenol A by electro-enhanced heterogeneous activation of
      peroxydisulfate using Mn-Zn ferrite from spent alkaline Zn-Mn batteries.
AB  - Mn-Zn ferrite (Mn0.6Zn0.4Fe2O4) was prepared by a gel method using spent alkaline
      Zn-Mn batteries as raw materials and employed as catalyst to degrade bisphenol A
      (BPA) by electro-enhanced heterogeneous activation of peroxydisulfate (PDS). The
      effects of initial pH, current density, PDS concentration, and Mn-Zn ferrite
      dosage on BPA removal were investigated. The formation of reactive radicals was
      verified by electron paramagnetic resonance (EPR) spectroscopy. The results of
      radical quenching experiments indicate that surface-bound sulfate and hydroxyl
      radicals played an important role in BPA removal. The stability of
      Mn0.6Zn0.4Fe2O4 catalyst was investigated by cycling experiments, which indicates
      Mn0.6Zn0.4Fe2O4 is stable and can be reused. This work also provides an
      alternative way for the reutilization of spent alkaline Zn-Mn batteries.

PMID- 29655112
TI  - Polarized electrode enhances biological direct interspecies electron transfer for
      methane production in upflow anaerobic bioelectrochemical reactor.
AB  - The influence of polarized electrodes on the methane production, which depends on
      the sludge concentration, was investigated in upflow anaerobic bioelectrochemical
      (UABE) reactor. When the polarized electrode was placed in the bottom zone with a
      high sludge concentration, the methane production was 5.34 L/L.d, which was 53%
      higher than upflow anaerobic sludge blanket (UASB) reactor. However, the methane
      production was reduced to 4.34 L/L.d by placing the electrode in the upper zone
      of the UABE reactor with lower sludge concentration. In the UABE reactor, the
      methane production was mainly improved by the enhanced biological direct
      interspecies electron transfer (bDIET) pathway, and the methane production via
      the electrode was a minor fraction of less than 4% of total methane production.
      The polarized electrodes that placed in the bottom zone with a high sludge
      concentration enhance the bDIET for methane production in the UABE reactor and
      greatly improve the methane production.

PMID- 29655113
TI  - Evaluation of noise and blur effects with SIRT-FISTA-TV reconstruction algorithm:
      Application to fast environmental transmission electron tomography.
AB  - Fast tomography in Environmental Transmission Electron Microscopy (ETEM) is of a
      great interest for in situ experiments where it allows to observe 3D real-time
      evolution of nanomaterials under operating conditions. In this context, we are
      working on speeding up the acquisition step to a few seconds mainly with
      applications on nanocatalysts. In order to accomplish such rapid acquisitions of
      the required tilt series of projections, a modern 4K high-speed camera is used,
      that can capture up to 100 images per second in a 2K binning mode. However, due
      to the fast rotation of the sample during the tilt procedure, noise and blur
      effects may occur in many projections which in turn would lead to poor quality
      reconstructions. Blurred projections make classical reconstruction algorithms
      inappropriate and require the use of prior information. In this work, a
      regularized algebraic reconstruction algorithm named SIRT-FISTA-TV is proposed.
      The performance of this algorithm using blurred data is studied by means of a
      numerical blur introduced into simulated images series to mimic possible
      mechanical instabilities/drifts during fast acquisitions. We also present
      reconstruction results from noisy data to show the robustness of the algorithm to
      noise. Finally, we show reconstructions with experimental datasets and we
      demonstrate the interest of fast tomography with an ultra-fast acquisition
      performed under environmental conditions, i.e. gas and temperature, in the ETEM.
      Compared to classically used SIRT and SART approaches, our proposed SIRT-FISTA-TV
      reconstruction algorithm provides higher quality tomograms allowing easier
      segmentation of the reconstructed volume for a better final processing and
      analysis.

PMID- 29655114
TI  - Long-term treatment effect of trauma-affected refugees with flexible cognitive
      behavioural therapy and antidepressants.
AB  - Few studies exist on the long-term effect of treatment of trauma-affected
      refugees. The purpose of this study was to estimate the long-term treatment
      effects of cognitive behavioural therapy and antidepressants (sertraline and
      mianserin) in trauma-affected refugees. Follow-ups were conducted 6 and 18 months
      after a randomised controlled clinical trial. The included patients were refugees
      with war-related traumatic experiences, PTSD and without psychotic disorders. We
      found a small improvement over time in PTSD, depression and anxiety symptoms and
      level of functioning, but the improvement was not associated with any specific
      treatment. Personality change after catastrophic experiences and life events
      influenced the symptom level at all follow-ups while depression at completion of
      treatment was associated with a steeper decline in symptom load at the follow
      ups. In spite of the limited decline in symptom scores and treatment effects
      immediately after treatment, the condition of the treated trauma-affected
      refugees was significantly improved 6 and 18 months after treatment although the
      improvement was small.

PMID- 29655115
TI  - Depressive symptoms, post-traumatic stress symptoms and suicide risk among
      graduate students: The mediating influence of emotional regulatory self-efficacy.
AB  - The current study was to examine the relationship among depressive symptoms, post
      traumatic stress symptoms, emotion regulatory self-efficacy and suicide risk. A
      cross-sectional survey was conducted among 3257 graduate students from a medical
      college of China. Lifetime prevalence of suicidal ideation, plan and attempt were
      25.7%, 1.6%, 1.1%, respectively, with one-year suicidal ideation showing at 6.3%.
      Structural equation modeling was employed to examine the relative contribution of
      depressive symptoms, post-traumatic stress symptoms and emotion regulatory self
      efficacy on suicide risk. Structural equation model had a highly satisfactory fit
      [chi2 = 7.782, df = 4, p = 0.096; RMSEA = 0.021; CFI = 0.992; GFI = 0.997]. Post
      traumatic stress symptoms had a direct effect and an indirect effect on suicide
      risk via emotion regulatory self-efficacy. Depressive symptoms also had a direct
      effect and an indirect effect on suicide risk via emotion regulatory self
      efficacy. The depressive and post-traumatic stress symptoms increased the risk of
      suicide risk, but the variable of emotion regulatory self-efficacy would be
      served as a buffering factor, decreasing the risk of suicide. The interaction
      term of depressive symptoms and post-traumatic stress symptoms had a direct
      effect on suicide risk. A significant interactive effect of depressive and post
      traumatic stress symptoms on suicide risk was found.

PMID- 29655116
TI  - The assessment of serum lipid profiles of children with attention deficit
      hyperactivity disorder.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent
      psychiatric disorders in children and the pathophysiology remains obscure. Some
      studies show that lipid imbalances are associated with ADHD etiology. We studied
      the association of serum total cholesterol, high-density lipoprotein (HDL), low
      density lipoprotein (LDL), and triglyceride (TG) levels in ADHD. We examined 88
      children aged 8-12 years who were diagnosed with ADHD and 88 healthy children.
      The exclusion criteria were as follows: obesity, any psychotropic use in the last
      3 months, presence of a chronic disease and/or malignancy, history of medically
      treated lipid metabolism disease in family members, intelligence quotient (IQ) <
      70, and comorbidities, with the exception of oppositional defiant disorder. The
      sample was evaluated using a semi-structured clinical assessment interview and
      Conners' rating scales. Despite controlling for age, sex, and body mass index
      (BMI) variables, the total cholesterol and LDL levels were significantly higher
      in the ADHD group than the levels of healthy controls, whereas the TG and HDL
      cholesterol levels were similar among groups. Conners' rating scales, reflecting
      symptom severity, and total cholesterol, TG, HDL, and LDL levels of the ADHD
      group were not correlated. The study results support the difference in serum
      lipid and lipoprotein profiles of children with ADHD compared with healthy
      controls. This difference is thought to be related with changes in
      oxidant/antioxidant balance states in ADHD.

PMID- 29655117
TI  - Psychological vulnerability and resilience of Holocaust survivors engaged in
      creative art.
AB  - Although evidence demonstrates that engagement in art promotes favorable coping
      with trauma, this subject is underexplored among Holocaust survivors. Thus, the
      present study explored whether Holocaust survivors engaged in art differed from
      survivors not engaged in art in various markers of psychological vulnerability
      and resilience. The study further included non-Holocaust survivor comparisons,
      some engaged in art and some not, in order to assess whether engagement in art
      among Holocaust survivors relates to a unique psychological profile beyond art
      engagement in general. A sample of 154 community-dwelling older adults (mean age
      = 81.67, SD = 5.33, range = 73-97) reported exposure to the Holocaust, current
      engagement in art, posttraumatic stress disorder (PTSD) symptoms, general
      psychological distress, resilience and subjective perceptions of age and aging.
      Holocaust survivors (regardless of whether they engaged in art or not) reported
      higher PTSD symptoms relative to comparisons. However, Holocaust survivors who
      engaged in art reported higher resilience than all other groups (survivors not
      engaged in art and comparisons engaged and not engaged in art). To the best of
      our knowledge, these findings are the first quantitative evidence pointing toward
      a link between engagement in art and positive coping with the Holocaust. These
      findings have important implications for clinicians working with Holocaust
      survivors.

PMID- 29655118
TI  - Effects of multi-walled carbon nanotube materials on Ruditapes philippinarum
      under climate change: The case of salinity shifts.
AB  - The toxicity of carbon nanotubes (CNTs) is closely related to their physico
      chemical characteristics as well as the physico-chemical parameters of the media
      where CNTs are dispersed. In a climate change scenario, changes in seawater
      salinity are becoming a topic of concern particularly in estuarine and coastal
      areas. Nevertheless, to our knowledge no information is available on how salinity
      shifts may alter the sensitivity (in terms of biochemical responses) of bivalves
      when exposed to different CNTs. For this reason, a laboratory experiment was
      performed exposing the Manila clam Ruditapes philippinarum, one of the most
      dominant bivalves of the estuarine and coastal lagoon environments, for 28 days
      to unfunctionalized multi-walled carbon nanotube MWCNTs (Nf-MWCNTs) and
      carboxylated MWCNTs (f-MWCNTs), maintained at control salinity (28) and low
      salinity 21. Concentration-dependent toxicity was demonstrated in individuals
      exposed to both MWCNT materials and under both salinities, generating alterations
      of energy reserves and metabolism, oxidative status and neurotoxicity compared to
      non-contaminated clams. Moreover, our results showed greater toxic impacts
      induced in clams exposed to f-MWCNTs compared to Nf-MWCNTs. In the present study
      it was also demonstrated how salinity shifts altered the toxicity of both MWCNT
      materials as well as the sensitivity of R. philippinarum exposed to these
      contaminates in terms of clam metabolism, oxidative status and neurotoxicity.

PMID- 29655119
TI  - Medical revalidation as professional regulatory reform: Challenging the power of
      enforceable trust in the United Kingdom.
AB  - For more than two decades, international healthcare crises and ensuing political
      debates have led to increasing professional governance and regulatory policy
      reform. Governance and policy reforms, commonly representing a shift from
      embodied trust in professionals to state enforceable trust, have challenged
      professional power and self-regulatory privileges. However, controversy remains
      as to whether such policies do actually shift the balance of power and what the
      resulting effects of policy introduction would be. This paper explores the roll
      out and operationalisation of revalidation as medical regulatory reform within a
      United Kingdom National Health Service hospital from 2012 to 2013, and its impact
      upon professional power. Revalidation policy was subject to the existing
      governance and management structures of the organisation, resulting in the formal
      policy process being shaped at the local level. This paper explores how the
      disorganised nature of the organisation hindered rather than facilitated robust
      processes of professional governance and regulation, fostering formalistic rather
      than genuine professional engagement with the policy process. Formalistic
      engagement seemingly assisted the medical profession in retaining self-regulatory
      privileges whilst maintaining professional power over the policy process. The
      paper concludes by challenging the concept of state enforceable trust and the
      theorisation that professional groups are effectively regulated and controlled by
      means of national and organisational objectives, such as revalidation.

PMID- 29655120
TI  - Increased stiffness of collagen fibrils following cyclic tensile loading.
AB  - Alterations in mechanical loading can induce growth and remodeling in soft
      connective tissues. Numerous studies have measured changes in the collagen
      structure and mechanical properties of cellularized native and engineered tissues
      in response to cyclic mechanical loading. However, a recent experimental study
      demonstrated that cyclic loading also caused significant stiffening and
      strengthening of acellular collagen constructs. In this work, we developed an
      anisotropic hyperelastic model of the collagen constructs to investigate whether
      the measured changes in the tissue-level properties can be attributed to changes
      in the anisotropic collagen structure or mechanical properties of the collagen
      fibrils. The model parameters describing the elastic properties, damage
      properties, and morphology of the fibril were fit to the stress-stretch response
      measured for the constructs subjected to different preconditioning strains and
      cycles. The results showed that the changes in the collagen anisotropy measured
      in experiments were insufficient to explain the increase in the stiffness and
      strength of the collagen constructs with cyclic loading and that the increase in
      the strength of the collagen constructs may be attributed mainly to the increase
      in the effective stiffness of the fibrils. These findings suggest that mechanical
      loading can induce changes in the stiffness and failure properties of the
      collagen fibril network through passive chemomechanical processes in addition to
      active cellular processes.

PMID- 29655121
TI  - Effect of microstructure on the mechanical properties of lithium disilicate glass
      ceramics.
AB  - The mechanical properties of lithium disilicate glass-ceramics depend on various
      factors, a prominent one being their microstructure. The aim of this review
      article is to elucidate the effect of processing parameters such as annealing
      temperature, holding time, number of heating stages and chemical composition and
      additives on the microstructure and physical properties of these glass-ceramics.

PMID- 29655122
TI  - Betavoltaic battery performance: Comparison of modeling and experiment.
AB  - A verification of the Monte Carlo simulation software for the prediction of short
      circuit current value is carried out using the Ni-63 source with the activity of
      2.7 mCi/cm2 and converters based on Si p-i-n diodes and SiC and GaN Schottky
      diodes. A comparison of experimentally measured and calculated short circuit
      current values confirms the validity of the proposed modeling method, with the
      difference in the measured and calculated short circuit current values not
      exceeding 25% and the error in the predicted output power values being below 30%.
      Effects of the protective layer formed on the Ni-63 radioactive film and of the
      passivating film on the semiconductor converters on the energy deposited inside
      the converters are estimated. The maximum attainable betavoltaic cell parameters
      are estimated.

PMID- 29655123
TI  - Demonstration of the bactericidal effects of the boron neutron capture reaction.
AB  - This pilot study represents a paradigm shift, using BNCT for the treatment of
      bacterial overgrowth on surgically implanted medical devices. In this study,
      titanium diboride disks were inoculated with S. aureus and irradiated in a
      thermal neutron beam. After a delivery of 2.6 * 1012 n/cm2 the surviving fraction
      of S. aureus on an irradiated disk was 3.1 * 10-5 when compared with non
      irradiated controls. This pilot study demonstrates proof of principle of boron
      neutron capture therapy for infection control (BNCIC).

PMID- 29655124
TI  - Design of a nitrogen purification system with cryogenic method for neutrino
      detection.
AB  - In order to detect the neutrino with liquid scintillation detector, high-purity
      nitrogen is essential for gas stripping in this detector. Therefore, it is
      necessary to design a purification system for the detector to purify nitrogen.
      Using the method of low temperature adsorption for the purification system, the
      key designs including the flow path, the adsorber and the selection of activated
      carbon, are introduced in this study. In these designs, the selection of
      activated carbon is the most important because the adsorption characteristic of
      the carbon is related to the performance of the purification system. The method
      of grand canonical ensemble Monte Carlo is adopted to simulate the adsorption of
      radon by the activated carbon with its slit pore model. Using this method, the
      working temperature and the key characteristic of the activated carbon are
      obtained.

PMID- 29655125
TI  - Improved non-destructive method for 90Sr activity determination in aqueous
      solutions using Monte Carlo simulation.
AB  - The development of new methods and improvements of existing methods for the
      specific activity determination of 90Sr and other distinct beta emitters has been
      of considerable interest. The reason for this interest is that the notably small
      number of methods that are able to meet all the set criteria, such as reliability
      of the results, measurement uncertainty and time, and minimum production of
      radioactive waste, as well as applicability to various samples with reference to
      their nature, geometry and composition. In this paper, two methods for rapid 90Sr
      activity determination based on Monte Carlo simulations are used, one for a Si
      semiconductor detector for beta spectrometric measurements and the other for the
      Geiger-Muller (GM) ionization probe. To improve the reliability of the
      measurement results, samples with high and low strontium activity solutions were
      prepared in the form of dry residues. The results of the proposed methodology
      were verified with a standard method using a liquid scintillation counter, and
      notably good agreements are achieved.

PMID- 29655126
TI  - Monte Carlo simulation of the responses of gaseous effluent monitors to
      radioactive isotopes.
AB  - This paper discusses use of Monte Carlo simulations to facilitate testing and
      calibration of a gaseous effluent monitor (GEM). MCNP5 was used to simulate
      responses of the 131I and 41Ar GEM detecting units exposed to specific
      radioactive sources. The agreement between the MCNP5 predictions and experimental
      measurements is good enough to validate the MCNP5 model. It has been demonstrated
      that the Monte Carlo code is a powerful and useful tool to determine accurate
      detector responses and facilitate the calibration process of this type of the
      monitors.

PMID- 29655127
TI  - Gamma spectrum and coincidence summation simulations with Geant4 in the analysis
      of radionuclide using BEGe detector.
AB  - A Geant4 application has been developed to simulate the gamma spectrum of a BEGe
      detector. The summation effects were encompassed for both random and true
      coincidences through a time-based approach. The application well reproduces the
      typical spectral features such as full energy peaks, escape peaks, summation
      peaks and Compton/backscatter continuum. The simulated gamma response is
      consistent with empirical data within 3%, while simulations of the X-ray and
      baseline regions are valid within a 10% deviation.

PMID- 29655128
TI  - Analysis on the emission and potential application of Cherenkov radiation in
      boron neutron capture therapy: A Monte Carlo simulation study.
AB  - This paper was aimed to explore the physics of Cherenkov radiation and its
      potential application in boron neutron capture therapy (BNCT). The Monte Carlo
      toolkit Geant4 was used to simulate the interaction between the epithermal
      neutron beam and the phantom containing boron-10. Results showed that Cherenkov
      photons can only be generated from secondary charged particles of gamma rays in
      BNCT, in which the 2.223 MeV prompt gamma rays are the main contributor. The
      number of Cherenkov photons per unit mass generated in the measurement region
      decreases linearly with the increase of boron concentration in both water and
      tissue phantom. The work presented the fundamental basis for applications of
      Cherenkov radiation in BNCT.

PMID- 29655130
TI  - The whole lupus: Articulating biosocial interplay in systemic lupus erythematosus
      epidemiology and population disparities.
AB  - Systemic lupus erythematosus (SLE), commonly known simply as lupus, is an
      autoimmune disease in which the body's immune system attacks healthy tissue and
      organs. Characteristic of the disease is a disproportionate effect on women and
      communities of color, both in terms of prevalence and severity of symptoms. Lupus
      is also both genetically driven and subject to external environmental conditions,
      many with place based corollaries. Thus, lupus presents a series of complex and
      intersecting biosocial questions regarding its origin and treatment, questions
      which transdisciplinary approaches are uniquely suited to address. In this paper,
      we propose a framework, incorporating critical approaches to the production of
      embodied formations of race and gender as well as new understandings of the
      impact of environmental conditions and lived experience at the genetic level,
      that can direct future research into lupus that is both more inclusive of a range
      of influences and more precise in its ability to treat and diagnose the disease.

PMID- 29655129
TI  - Surviving the housing crisis: Social violence and the production of evictions
      among women who use drugs in Vancouver, Canada.
AB  - Single room accommodation (SRA) housing is among the only forms of accessible
      housing to marginalized women who use illicit drugs in many urban settings.
      However, SRA housing environments may create specific health and drug risks for
      women. Little research has examined the gendered mechanisms contributing to
      housing vulnerability for women who use drugs and the subsequent ways they aim to
      mitigate harm. This study examines the gendered vulnerabilities to, and harms
      stemming from, evictions from SRAs in Vancouver, Canada. Qualitative interviews
      were conducted with 56 people who use drugs who were recently evicted (past 60
      days) from SRAs in Vancouver's Downtown Eastside neighbourhood, 19 of whom
      identified as women which informed this analysis. Participants were recruited by
      Peer Researcher Assistants for baseline and follow-up interviews three to six
      months later. Interview transcripts were analyzed thematically and interpreted by
      drawing on concepts of social violence. Findings underscore how gendered violence
      and forms of social control operationalized within SRAs normalized violence
      against women and restricted their agency. Surveillance mechanisms increased
      women's experiences of violence as they sought to evade such interventions. Post
      eviction, women faced pronounced vulnerability to harm which reinforced their
      social and spatial marginality within a drug scene. Collectively, women's
      experiences within SRAs highlight how the hybrid forms of disciplinary mechanisms
      used within these housing environments significantly impacted women's experiences
      of harm. Greater attention to the impacts of housing and building policies on
      women who use drugs is needed to better address the morbidity and mortality of
      this population.

PMID- 29655131
TI  - Synthesis of N-acetyl-l-cysteine capped Mn:doped CdS quantum dots for
      quantitative detection of copper ions.
AB  - In this work, a new assembled copper ions sensor based on the Mn metal-enhanced
      fluorescence of N-acetyl-l-cysteine protected CdS quantum dots (NAC-Mn:CdS QDs)
      was developed. The NAC and Mn:CdS QDs nanoparticles were assembled into NAC
      Mn:CdS QDs complexes through the formation of CdS and MnS bonds. As compared to
      NAC capped CdS QDs, higher fluorescence quantum yields of NAC-Mn:CdS QDs was
      observed, which is attributed to the surface plasmon resonance of Mn metal. In
      addition, the fluorescence intensity of as-formed complexes weakened in the
      presence of copper ions. The decrease in fluorescence intensity presented a
      linear relationship with copper ions concentration in the range from 0.16-3.36MUM
      with a detection limit of 0.041MUM . The characterization of as-formed QDs was
      analyzed by photoluminescence (PL), ultra violet-visible (UV-vis), X-ray
      diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and energy
      dispersive spectroscopy (EDS) respectively. Furthermore, the recoveries and
      relative standard deviations of Cu2+ spiked in real water samples for the intra
      day and inter-day analyses were 88.20-117.90, 95.20-109.90, 0.80-5.80 and 1.20
      3.20%, respectively. Such a metal-enhanced QDs fluorescence system may have
      promising application in chemical and biological sensors.

PMID- 29655132
TI  - Adenomyosis and urinary system symptoms.
AB  - OBJECTIVE: This study aims to investigate the presence and incidence of
      overactive bladder (OAB) syndrome in patients diagnosed with adenomyosis and to
      evaluate the impacts of urinary symptoms on the quality of life of the patients.
      MATERIALS AND METHODS: A total of 108 individuals including 50 patients with
      adenomyosis and 58 controls who were admitted to the Obstetrics and Gynecology
      Department of Bursa, Cekirge State Hospital and Derince Training and Research
      Hospital between April 2015 and December 2015 were included. The Urogenital
      Distress Inventory (UDI-6) and Incontinence Impact Questionnaire (IIQ-7) were
      used to evaluate symptoms. RESULTS: Irritative urinary symptoms such as nocturia
      and frequency were seen more frequently in the adenomyosis group (p = 0.001 and p
      = 0.035). Overactive bladder symptoms were more common in the adenomyosis group
      (p = 0.0001). CONCLUSION: Our study showed that symptoms of urinary tract
      symptoms are common in patients with adenomyosis, which adversely affect the
      quality of life.

PMID- 29655133
TI  - Determinants of staff commitment to hip protectors in long-term care: A cross
      sectional survey.
AB  - BACKGROUND: If worn, certain models of hip protectors are highly effective at
      preventing hip fractures from falls in residents of long-term care, but modest
      acceptance and adherence have limited the effectiveness of hip protectors.
      Residents of long-term care are more likely to accept the initial offer of hip
      protectors and to adhere to recommendations concerning the use of hip protectors
      when staff are committed to supporting the application of hip protectors. Yet, we
      know very little about the nature of and factors associated with staff commitment
      to hip protectors in long-term care. OBJECTIVE: To identify factors associated
      with staff commitment to hip protectors in long-term care. DESIGN: A cross
      sectional survey. SETTING: Thirteen long-term care homes (total beds = 1816) from
      a single regional health district in British Columbia, Canada. PARTICIPANTS: A
      convenience sample of 535 paid staff who worked most of their time (>50% of work
      hours) at a participating long-term care home, for at least one month, and for at
      least 8 h per week. We excluded six (1.1%) respondents who were unaware of hip
      protectors. Of the remaining 529 respondents, 90% were female and 55% were health
      care assistants. METHODS: Respondents completed the Commitment to Hip Protectors
      Index to indicate their commitment to hip protectors. We used Bayesian Model
      Averaging logistic regression to model staff commitment as a function of personal
      variables, experiences with hip protectors, intraorganizational communication and
      influence, and organizational context. RESULTS: Staff commitment was negatively
      related to organizational tenure >20 years (posterior probability = 97%; logistic
      regression coefficient = -0.28; 95% confidence interval = -0.48, -0.08), and
      awareness of a padded hip fracture (100%; -0.57; -0.69, -0.44). Staff commitment
      was positively related to the existence of a champion of hip protectors within
      the home (100%; 0.24; 0.17, 0.31), perceived quality of intraorganizational
      communication (100%; 0.04; 0.02, 0.05), extent of mutual respect between
      residents and staff and perceived contribution to quality of life of the
      residents they serve (100%; 0.10; 0.05, 0.15), and frequency of transformational
      leadership practices by respondents' primary supervisors (100%; 0.01; 0.01,
      0.02). CONCLUSIONS: We provide novel insight into the factors governing staff
      commitment to hip protectors in long-term care. Targeting of these factors could
      improve acceptance and adherence with hip protectors, thereby contributing to
      enhanced effectiveness of hip protectors to prevent hip fractures in long-term
      care.

PMID- 29655135
TI  - Erector spinae plane block provides sufficient surgical anesthesia for ileostomy
      closure in a high-risk patient.

PMID- 29655134
TI  - Understanding the link between contingency management and smoking cessation: The
      roles of sex and self-efficacy.
AB  - INTRODUCTION: Little is known about the mechanisms linking contingency management
      (CM) treatment with smoking cessation, and recent research suggests that the CM
      approach is associated with better smoking cessation outcomes among females than
      males. The current study investigated self-efficacy as a potential mechanism
      through which CM treatment influences smoking cessation, and explored whether
      these relationships differed by sex. METHODS: Participants (N = 139) were
      primarily Black (63.3%) and female (57.6%) adults enrolled in a safety-net
      hospital smoking cessation program. Participants received usual care (UC), which
      included pharmacotherapy and counseling sessions (n = 66) or a CM intervention
      (UC + 4 weeks of small, abstinence contingent financial incentives; n = 73). Self
      efficacy for quitting was measured on the day after quitting with the Self
      Efficacy Scale/Confidence (SESC) questionnaire. Mediation analyses were conducted
      to evaluate the indirect effects of treatment group on biochemically-verified
      abstinence (4-weeks post-quit) via self-efficacy, and moderated mediation
      analyses were conducted to evaluate the moderating role of sex. RESULTS: Self
      efficacy was not found to mediate the relations between CM treatment and smoking
      cessation in the overall sample. However, analyses indicated a significant
      moderating effect of sex on the indirect effect of treatment group on smoking
      cessation through self-efficacy (each of the 3 SESC subscales). Specifically,
      there was a stronger association between CM and greater self-efficacy among
      females than males. CONCLUSION: Findings suggest that CM treatment had a
      differing impact on self-efficacy among males and females, which in turn
      influenced the likelihood of smoking cessation.

PMID- 29655136
TI  - Carbon dioxide/brine wettability of porous sandstone versus solid quartz: An
      experimental and theoretical investigation.
AB  - HYPOTHESIS: Wettability plays an important role in underground geological storage
      of carbon dioxide because the fluid flow and distribution mechanism within porous
      media is controlled by this phenomenon. CO2 pressure, temperature, brine
      composition, and mineral type have significant effects on wettability. Despite
      past research on this subject, the factors that control the wettability variation
      for CO2/water/minerals, particularly the effects of pores in the porous substrate
      on the contact angle at different pressures, temperatures, and salinities, as
      well as the physical processes involved are not fully understood. EXPERIMENTS: We
      measured the contact angle of deionised water and brine/CO2/porous sandstone
      samples at different pressures, temperatures, and salinities. Then, we compared
      the results with those of pure quartz. Finally, we developed a physical model to
      explain the observed phenomena. FINDINGS: The measured contact angle of sandstone
      was systematically greater than that of pure quartz because of the pores present
      in sandstone. Moreover, the effect of pressure and temperature on the contact
      angle of sandstone was similar to that of pure quartz. The results showed that
      the contact angle increases with increase in temperature and pressure and
      decreases with increase in salinity.

PMID- 29655137
TI  - Visible light-enhanced electrocatalytic alcohol oxidation based on two
      dimensional Pt-BiOBr nanocomposite.
AB  - Photoelectrocatalytic oxidation based on noble/semiconductor has been a renewed
      interest in the past decades. The lack of high-performance semiconductor support
      remains a challenge for the harvesting and conversion of solar energy. Here, we
      report the syntheses of two dimensional (2D) BiOBr nanosheets with the
      superiorities of suitable band gaps, nontoxic, corrosion resistant and so on.
      These features enable them unprecedented performance for acting as the visible
      light-driven support towards alcohol oxidation. Firstly, the pure BiOBr nanosheet
      has negligible activity towards alcohol oxidation. After the deposition of Pt
      nanoparticles (NPs), the as-prepared Pt-BiOBr composites show superior
      electrocatalytic activities towards ethanol and methanol oxidation reaction under
      visible light irradiation, with the mass activities of 929.8 mA mg-1Pt and 751.7
      mA mg-1Pt, 6.0 and 28.4-fold enhancements than those under dark condition,
      respectively. The great enhancement in the photoelectrocatalytic performances can
      be attributed to the unique 2D nanostructure, synergistic and photocatalytic
      effects. This work may pave up a new route for designing the desirable
      semiconductor supports for the decoration of the noble metal catalysts, showing
      significant promise for the application of fuel cells.

PMID- 29655138
TI  - Self-cleaning superhydrophobic nanocomposite surfaces generated by laser pulse
      heating.
AB  - Micro- and nanostructured surfaces are known to induce anti-wetting and self
      cleaning properties. However, traditional formation of these structures is
      difficult and requires high-resolution micro- and nanofabrication methods. Here,
      we demonstrate a facile method for the formation of superhydrophobic self
      cleaning surfaces by laser pulse heating of a carbon nanotube-polymer composite.
      Laser treatment exposes a carbon nanotube network which controls surface wetting
      properties. Advancing and receding contact angle measurements demonstrate that
      these surfaces are superhydrophobic. Additionally, surfaces show anti-wetting and
      self-cleaning properties.

PMID- 29655139
TI  - The effects of melamine on the formation of carbon xerogel derived from
      resorcinol and formaldehyde and its performance for supercapacitor.
AB  - Carbon aerogel/xerogel can be easily tuned to have hierarchical pores ranging
      from micropores to macropores. Nitrogen doping is considered to enhance the
      wettability and conductivity of the carbon electrode, hence improve the
      electrochemical performance. To prepare N-doped carbon xerogel and study the
      effects on the structure and the electrochemical performance of resorcinol and
      formaldehyde derived carbon xerogel, a series of Resorcinol-Melamine-Formaldehyde
      derived N-doped carbon xerogel were prepared by a facile sol-gel process and
      ambient drying method. With the increasing amount of melamine, the inside
      channels become larger, which contributes to faster ion transport and smaller
      charge transfer resistance (Rct). The Nitrogen content in carbon xerogel is also
      increased, enhancing the capacitance of carbon electrode by pseudocapacity
      effect, while damaging the rate performance by introducing more defects and
      larger degree of disorder. As a result, the best electrochemical performance is
      achieved in the RM-6-4 sample (resorcinol:melamine = 6:4), showing the largest
      capacitance of 139 F g-1.

PMID- 29655140
TI  - Synthesis of fluorinated graphene oxide by using an easy one-pot
      deoxyfluorination reaction.
AB  - The fluorination of two types of graphene oxides conducted by an easy and
      scalable deoxyfluorination reaction is reported. This reaction was carried out
      using diethylaminodifluorosulfinium tetrafluoroborate, a stable compound and an
      efficient reagent for replacing oxygenated functional groups of graphene oxide by
      fluoride. The graphene oxide produced by the Hummers' method (GOH) showed lower
      reactivity than that produced by the Brodie's method (GOB). X-ray photoelectron
      spectroscopy indicated that the highest fluorination degree achieved was 4.7 at.%
      when GOB was used, and the CF character corresponds to semi-ionic bonds.
      Additionally, a partial reduction of GO was concomitant with the
      functionalization reaction. The deoxyfluorination reaction changed the
      crystalline structure of GO, favoring the reconstruction of Csp2 structure of the
      graphene lattice and reducing the number of stacked layers. The fluorination led
      to the modification of the electronic band structure of this material, increasing
      the band gap from 2.05 eV for GOB to 3.88 eV for fluorinated GOB, while for GOH
      the low flurionation led to a slight increase of the band gap, from 3.48 eV to
      3.57 eV.

PMID- 29655141
TI  - Structural properties and catalytic activity of a novel ternary CuO/gC3N4/Bi2O3
      photocatalyst.
AB  - In the present study, CuO/gC3N4/Bi2O3 composite is constructed as a ternary
      visible light active photocatalyst. Since CuO plays a critical role in enhancing
      the photocatalytic activity of the formed composite, its structural properties
      are particularly studied using synchrotron X-ray absorption spectroscopy (XAS),
      including X-ray absorption near edge structure (XANES) and extended X-ray
      absorption fine structure (EXAFS). XANES confirms the presence of Cu species with
      +2 oxidation state in the form of CuO. EXAFS furthermore confirms that each Cu
      cation is coordinated to four O anions in an approximately square planar
      configuration. The length of the Cu-O coordination is estimated to be 1.92 A,
      slightly shorter than that of bulk CuO (1.95 A). The CuO/gC3N4/Bi2O3 composite
      exhibits highly enhanced photocatalytic activity in the 2,4-dichlorophenol
      decomposition under visible light. The enhanced photocatalytic activity is due to
      the increased population of electrons and the successful consumption of the
      photoproduced electrons by the dissolved oxygen through the one-electron transfer
      reaction.

PMID- 29655142
TI  - Silver nanoparticles-incorporated Nb2O5 surface passivation layer for efficiency
      enhancement in dye-sensitized solar cells.
AB  - Guiding and capturing photons at the nanoscale by means of metal nanoparticles
      and interfacial engineering for preventing back-electron transfer are well
      documented techniques for performance enhancement in excitonic solar cells.
      Drifting from the conventional route, we propose a simple one-step process to
      integrate both metal nanoparticles and surface passivation layer in the porous
      photoanode matrix of a dye-sensitized solar cell. Silver nanoparticles and Nb2O5
      surface passivation layer are simultaneously deposited on the surface of a highly
      porous nanocrystalline TiO2 photoanode, facilitating an absorption enhancement in
      the 465 nm and 570 nm wavelength region and a reduction in back-electron transfer
      in the fabricated dye-sensitized solar cells together. The TiO2 photoanodes were
      prepared by spray pyrolysis deposition method from a colloidal solution of TiO2
      nanoparticles. An impressive 43% enhancement in device performance was
      accomplished in photoanodes having an Ag-incorporated Nb2O5 passivation layer as
      against a cell without Ag nanoparticles. By introducing this idea, we were able
      to record two benefits - the metal nanoparticles function as the absorption
      enhancement agent, and the Nb2O5 layer as surface passivation for TiO2
      nanoparticles and as an energy barrier layer for preventing back-electron
      transfer - in a single step.

PMID- 29655143
TI  - Effect of PEGylation on the stability of thermoresponsive nanogels.
AB  - In biomedical applications, PEGylation is frequently utilized to enhance the
      nanoparticles (NPs) capability for long systemic circulation times in the blood
      and it is also crucial to stabilize the NPs and thereby minimize their ability to
      agglomerate. In this study, we have synthesized poly(N-isopropylacrylamide)
      (PNIPAAM) nanogels with covalently attached PEG chains of different length and
      PEG coating densities. It is observed that in the absence of PEG coating the
      nanogels aggregate at elevated temperatures. It is found from dynamic light
      scattering (DLS) that both increased PEG length and enhanced PEG coating density
      have crucial influence on the stability of the nanogels. The results show that
      long PEG chains have a stronger impact on the shielding ability of the PEG layer
      on the nanogels than a high coating density of short chains. The small angle
      neutron scattering (SANS) measurements on PEG-coated nanogels indicate that the
      coated layer contract at higher temperatures but still the particles are
      stabilized. The bare PNIPAAM nanogels can be electrostatically stabilized by
      adding a small amount of an ionic surfactant.

PMID- 29655144
TI  - Rational synthesis of graphene-encapsulated uniform MnMoO4 hollow spheres as long
      life and high-rate anodes for lithium-ion batteries.
AB  - In this manuscript, the graphene-encapsulated MnMoO4 hollow spheres (MnMoO4@G)
      synthesized by an effective strategy were reported. Benefiting from the
      intriguing hybrid architecture of hollow structure and conductive graphene
      network, the MnMoO4@G composite displays superior electrochemical performance
      with high specific capacity of 1142 mA h g-1, high reversible cycling stability
      of 921 mA h g-1 at a current density of 100 mA g-1 after 70 cycles, and stable
      rate performance (around 513 mA h g-1 at a current density of 4.0 A g-1). The
      remarkable battery performance can be attributed to the rational design of the
      architecture, which not only ensures the fast transport of electrons and lithium
      ions within the electrode material, but also effectively relax the stress induced
      by the insertion/extraction of lithium ions. This facile synthetic method can
      extend to other transition metal oxides with large volume excursions and poor
      electric conductivity and promotes the development of transition metal oxides as
      high-performance LIB anode material.

PMID- 29655145
TI  - Reliable and accurate extraction of Hamaker constants from surface force
      measurements.
AB  - A simple and accurate closed-form expression for the Hamaker constant that best
      represents experimental surface force data is presented. Numerical comparisons
      are made with the current standard least squares approach, which falsely assumes
      error-free separation measurements, and a nonlinear version assuming independent
      measurements of force and separation are subject to error. The comparisons
      demonstrate that not only is the proposed formula easily implemented it is also
      considerably more accurate. This option is appropriate for any value of Hamaker
      constant, high or low, and certainly for any interacting system exhibiting an
      inverse square distance dependent van der Waals force.

PMID- 29655146
TI  - Synthesis of DOPO-HQ-functionalized graphene oxide as a novel and efficient flame
      retardant and its application on polylactic acid: Thermal property, flame
      retardancy, and mechanical performance.
AB  - The fabrication of biodegradable polymer nanocomposites with improved flame
      retardancy has been an urgent task in practical because of the huge benefits of
      biodegradable polymers. In this work, 10-(2,5-dihydroxyl phenyl)-9,10-dihydro-9
      oxa-10-phosphaphenanthrene-10-oxide (DOPO-HQ)-functionalized graphene oxide (GO)
      (FGO-HQ) was used as a novel and highly efficient flame retardant (FR) to improve
      the flame retardancy of polylactide (PLA) nanocomposites. Contributed by the bi
      phase flame retardant action, including the physical barrier char in solid phase
      and the decreased flammable volatiles in gas phase, the resultant PLA/FGO-HQ
      nanocomposites presented excellent flame resistance at the loading of 6 wt% FR:
      UL-94 reached V-0 rating; peak heat release rate (PHRR) and total heat release
      (THR) decreased by 24.0% and 43.0%, respectively; smoke production rate (SPR) and
      total smoke release (TSR) decreased by 46% and 83%, respectively. For further
      confirming its flame-resistance mechanism, thermogravimetric analysis/infrared
      spectrometry (TG-IR) and Fourier transform infrared spectra (FT-IR), scanning
      electron microscope (SEM), and Raman spectroscopy were employed. Results
      indicated that the incorporation of FGO-HQ can effectively reduce the evaporation
      of flammable gaseous product in gas phase through quenching free radicals.
      Meanwhile, graphitized carbons are formed in the residual char and PLA/FGO-HQ
      sample can achieve a good thermal stability in the combustion with phosphorus
      containing compounds and aromatic structure in the solid phase. Furthermore, the
      tensile strength of PLA nanocomposites presented good mechanical properties with
      the addition of FR as well. These results suggested that the incorporation of FGO
      HQ FR not only improve the flame retardancy and thermal stability of
      biodegradable polymer nanocomposites but also without sacrificing their
      mechanical properties.

PMID- 29655147
TI  - Microstructural characteristics of surfactant assembly into a gel-like mesophase
      for application as an oil spill dispersant.
AB  - HYPOTHESIS: Polyoxyethylene (20) sorbitan monooleate (Tween 80) can be
      incorporated into the gel-like phase formed by L-alpha-phosphatidylcholine (PC)
      and dioctyl sulfosuccinate sodium salt (DOSS) for potential application as a gel
      like dispersant for oil spill treatment. Such gel-like dispersants offer
      advantages over existing liquid dispersants for mitigating oil spill impacts.
      EXPERIMENTS: Crude oil-in-saline water emulsions stabilized by the surfactant
      system were characterized by optical microscopy and turbidity measurements while
      interfacial tensions were measured by the spinning drop and pendant drop
      techniques. The microstructure of the gel-like surfactant mesophase was
      elucidated using small angle neutron scattering (SANS), cryo scanning electron
      microscopy (cryo-SEM), and 31P nuclear magnetic resonance (NMR) spectroscopy.
      FINDINGS: The gel-like phase consisting of PC, DOSS and Tween 80 is positively
      buoyant on water and breaks down on contact with floating crude oil layers to
      release the surfactant components. The surfactant mixture effectively lowers the
      crude oil-saline water interfacial tension to the 10-2 mN/m range, producing
      stable crude oil-in-saline water emulsions with an average droplet size of about
      7.81 um. Analysis of SANS, cryo-SEM and NMR spectroscopy data reveals that the
      gel-like mesophase has a lamellar microstructure that transition from rolled
      lamellar sheets to onion-like, multilamellar structures with increasing Tween 80
      content.

PMID- 29655148
TI  - Block copolymer-assisted synthesis of monodisperse colloidal patchy
      nanoparticles.
AB  - Amphiphilic block copolymers are able to assemble into spherical micelles in an
      aqueous solution. Spherical micelles are expected to adsorb on the surface of
      colloidal nanoparticles (NPs) through hydrogen-bonding interaction. Hence, it
      should be possible to guide the area-selective deposition of precursors onto the
      exposed surface of colloidal seeds, where no micelles are adsorbed. Using
      colloidal silica and polydopamine nanospheres as seeds, block copolymer F127 and
      P123 are used as surface modifiers to guide the controlled solution-phase
      deposition of precursors on a selectively exposed surface of seed NPs, leading to
      the formation of patchy NPs. Effects of the addition amount of tetraethoxysilane
      (TEOS), types of block copolymers, and the volume fraction of miscible organic
      solvents on the size and morphology of patchy silica NPs are investigated
      systematically through electron microscopic imaging. Block copolymer micelles
      adsorption model for the formation of colloidal patchy NPs is first proposed. Our
      study suggests that the shape and size of patchy silica NPs are determined by the
      amount of TEOS and dielectric constant of solution.

PMID- 29655149
TI  - Sulfonated graphene oxide as an adsorbent for removal of Pb2+ and methylene blue.
AB  - One of the major challenges encountered in some conventional nano-structured
      adsorbents such as graphene oxide (GO) and graphene is the structural limits
      including serious aggregation and hydrophilic surface in water. And the
      sulfanilic acid functionalized graphene oxide (SGO) can powerfully attract
      positively charged pollutants. Therefore, the SGO served as an adsorbent to
      remove dyes and toxic metal ions from aqueous solution were intensively
      investigated. At the same time the reduced sulfonated graphene oxide (rSGO),
      reduced graphene oxide (rGO), and graphene oxide (GO) were performed as the
      comparative samples. The results showed that the maximum adsorption capacities of
      SGO were 2530 mg/g for methylene blue and 415 mg/g for Pb2+, which was much
      higher than that of the contrast samples and adsorbents reported in literatures.
      The adsorption of SGO was investigated systematically including the saturated
      adsorption capacities, isotherm, and kinetic adsorption process. The SGO
      displayed high adsorption efficiency and superior adsorption capacity toward
      metal ions and dyes, which is mainly attribute to the good dispersibility and the
      multiple adsorption sites of SGO. These results are promising not only providing
      effective adsorbing heavy metal ions and organic dyes, but also gaining insights
      into adsorption mechanism of graphene materials.

PMID- 29655150
TI  - Enhanced room-temperature catalytic decomposition of formaldehyde on magnesium
      aluminum hydrotalcite/boehmite supported platinum nanoparticles catalyst.
AB  - Magnesium-aluminum hydrotalcite (Mg-Al HT)/boehmite (AlOOH) composite supported
      Pt catalysts were obtained via one-pot microemulsion synthesis of Mg-Al HT/AlOOH
      composite and NaBH4-reduction of Pt precursor processes. The catalytic
      performances of the catalysts were evaluated for formaldehyde (HCHO) removal at
      room temperature. The performance tests showed that the catalyst obtained by
      immobilizing Pt nanoparticles (NPs) on Mg-Al HT/AlOOH support with Al/Mg molar
      ratio equivalent to 9:1 (Pt/Al9Mg1) displayed a superior catalytic activity and
      stability for HCHO removal. In order to find out the causes of its higher
      activity, X-ray diffraction, transmission electron microscopy, N2
      adsorption/desorption, X-ray photoelectron spectroscopy, temperature programmed
      desorption of CO2 and reduction of H2 were used to analyze the physicochemical
      properties of Pt/Al9Mg1 and Pt/AlOOH. The remarkable catalytic performance of
      Pt/Al9Mg1 is mainly attributed to the relatively larger amount of surface oxygen
      species, and more reactive oxygen species led by the interaction of Mg-Al HT and
      AlOOH/Pt, and relatively larger number of weak base sites caused by Mg-Al HT. The
      formate species are the main reaction intermediate over Pt/Al9Mg1 during HCHO
      oxidation at room temperature, which could be further oxidized into CO2 and H2O
      in the presence of O2. This study might shed some light on further improving the
      catalytic performance of the catalyst for indoor air purification at room
      temperature.

PMID- 29655151
TI  - Fabrication of 2D SnS2/g-C3N4 heterojunction with enhanced H2 evolution during
      photocatalytic water splitting.
AB  - In this work, the 2D SnS2/g-C3N4 heterojunctions were successfully prepared by
      heating the homogeneous dispersion of SnS2 nanosheets and g-C3N4 nanosheets using
      a microwave muffle. SEM, TEM and HRTEM images indicated that the SnS2 nanosheets
      were loaded on the surface of the g-C3N4 nanosheets. The UV-vis spectra show that
      the absorption intensity of the as-prepared samples was increased and the
      absorption range was also extended from 420 nm to approximately 600 nm. The H2
      production rate over 5 wt% SnS2/g-C3N4 can reach 972.6 MUmol.h-1.g-1 under
      visible light irradiation (lambda > 420 nm) using TEOA as the sacrifice agent and
      Pt as the electron trap, which is 2.9 and 25.6 times higher than those of the
      pristine g-C3N4 and SnS2, respectively. According to the obtained PL spectra,
      photocurrent and EIS spectra, the enhanced performance for H2 generation over the
      heterojunctions is primarily ascribed to the rapid charge transfer arising from
      the suitable band gap positions leading to an improved photocatalytic
      performance. The recycling experiments indicated that the as-prepared composites
      exhibit good stability in H2 production. Additionally, a possible enhanced
      mechanism for H2 evolution was deduced based on the results obtained by various
      characterization techniques.

PMID- 29655152
TI  - The nature of hematite depression with corn starch in the reverse flotation of
      iron ore.
AB  - The function of corn starch and the significance of the order of addition of corn
      starch and mono ether amine in the reverse flotation of iron ore has been
      investigated. Understanding hematite depression with starch and the corresponding
      hydrophilic state involves consideration of adsorption with amine as well as
      flocculation of fine hematite. Captive bubble contact angle and micro-flotation
      experiments indicated that amine has an affinity towards both hematite and
      quartz, and that the role of starch is to hinder the adsorption of amine at the
      hematite surface so that flotation is inhibited. Micro-flotation results
      confirmed that quartz does not have affinity towards starch at pH 10.5. In
      addition to competitive adsorption, flocculation of fine hematite occurs and
      images from high resolution X-ray computed tomography (HRXCT) and cryo-SEM reveal
      further detail regarding floc structure. These results provide substantial
      evidence that the fine hematite particles are flocculated in the presence of corn
      starch, and flocculation is dependent on the particle size of hematite, with
      greater flocculation for finer particles. Thus, starch is playing a dual role in
      the reverse flotation of iron ore, acting as a depressant by hindering amine
      adsorption at the hematite surface in order to maintain the hydrophilic surface
      state of hematite, and acting as a flocculant to aggregate fine hematite
      particles, which if not flocculated, could diminish the flotation separation
      efficiency by being transported to the froth phase during reverse flotation.

PMID- 29655153
TI  - New rapid method to detect BCR-ABL fusion genes with multiplex RT-qPCR in one
      tube at a time.
AB  - Fast identification of BCR-ABL fusion genes is critical for precise diagnosis,
      risk stratification and therapy scheme selection in leukemia. More convenient
      methods are needed for quickly detection of the BCR-ABL fusion genes. Multiplex
      fluorescent reverse transcription quantitative real-time PCR (Multiplex RT-qPCR)
      methods are developed for detection of the at least 14 subtypes of BCR-ABL fusion
      genes in one tube at a time by using patients' bone marrow samples. The new
      Multiplex RT-qPCR method could quickly detect BCR-ABL fusion genes with
      sensitivity up to 10-106 copies. It can detect the fusion genes in patients' bone
      marrow samples containing any subtypes of the major bcr (M-bcr) e13a2, e14a2,
      e13a3 and e14a3, the minor bcr (m-bcr) e1a2 and e1a3, the micro bcr (MU-bcr)
      e19a2 and e19a3, and the nano bcr (n-bcr) e6a2 and e6a3. The specificity is
      comparable to the FISH methods. The cutoff for clinical diagnosis of BCR-ABL(+)
      is also determined by testing in clinical chronic myeloid leukemia samples. This
      is a new fast method with high sensitivity and specificity for clinical detection
      of BCR-ABL fusion genes. It will benefit the precise diagnosis, targeted therapy
      and minimal residual disease (MRD) monitoring in leukemia.

PMID- 29655154
TI  - Assessing the correlation of genotypic and phenotypic responses of indica rice
      varieties under drought stress.
AB  - Drought is one of the severe abiotic stress that affects the productivity of
      rice, an important staple crop that is consumed all over the world. The traits
      responsible for enhancing or adapting drought resistance in rice plants can be
      selected and studied to improve their growth under stress conditions. Experiments
      have been conducted on indica rice varieties comprising Sahabhagidhan as drought
      tolerant variety and IR64, MTU1010 categorized as drought sensitive varieties.
      Various root related biochemical and morphological traits such as root length,
      relative water content (RWC), xylem number, xylem area, proline content, and
      malondialdehyde content have been investigated for a comparative study of the
      plant response to drought stress in different rice varieties. The results of
      differential root transcriptome analysis have revealed that there is a notable
      difference in gene expression of OsPIP2;5 and OsNIP2;1 in various indica
      varieties of rice at different time periods of stress. The present work aims at
      assessing the correlation between genotypic and phenotypic traits that can
      contribute towards the emerging field of rice phenomics.

PMID- 29655155
TI  - Effect of side of the corpus luteum and pregnancy on estrogen and progesterone
      receptor expression and localization in the endometrium of mares.
AB  - The effect of side of corpus luteum on uterine gene expression and protein
      localization of estrogen receptor alpha (ERalpha) and progesterone receptor (PR)
      in healthy cyclic and pregnant mares 13 days after ovulation (day 0) was
      investigated. Transcervical biopsies were performed to collect endometrium
      ipsilateral and contralateral regarding the side of corpus luteum on day 13 post
      ovulation in cyclic (n = 6) and pregnant (n = 6) mares. Blood samples were
      collected daily from day 0 until the day of biopsy for 17beta-estradiol (E2) and
      progesterone (P4) determinations. Receptor expression was determined by
      immunohistochemistry and transcript expression by real time RT-PCR. Serum E2 and
      P4 concentrations were not affected by reproductive status. The contralateral
      horn presented higher percentage of positive cells for ERalpha than the
      ipsilateral horn (P < .05), but side did not affect PR. ERalpha showed low
      staining and no main effect of pregnancy was found, but pregnant mares had lower
      protein expression of PR (19.8 vs. 40.4 +/- 5.3%, P < .01). The contralateral
      horn tended to present higher expression of ERalpha mRNA (1.33 vs. 0.97 +/- 0.17,
      P < .10) and PR mRNA (1.96 vs. 1.57 +/- 0.52, P < .09). ERalpha mRNA relative
      expression was lower in the pregnant group (0.88 vs. 1.44 +/- 0.19, P < .05). The
      interaction of reproductive status and side of corpus luteum tended to affect PR
      mRNA expression as pregnant mares had a lower PR mRNA content in the ipsilateral
      horn than cyclic mares. To our knowledge, this is the first study that describes
      the behavior of steroid receptors in the endometrium of mares regarding side of
      corpus luteum.

PMID- 29655156
TI  - Interactive effect of climate factors, biochar and insecticide chlorpyrifos on
      methane consumption and microbial abundance in a tropical Vertisol.
AB  - Climate change may increase the pest infestation leading to intensive use of
      insecticides. However, the effect of insecticide and climate factors on soil
      methane (CH4) consumption is less understood. A laboratory experiment was carried
      out to evaluate the effect of temperature (15  degrees C, 35  degrees C, and 45 
      degrees C), moisture holding capacity (MHC) (60%, 100%), biochar (0%, 1%) and
      chlorpyrifos (0 ppm, 10 ppm) on CH4 consumption and microbial abundance in a
      tropical Vertisol of central India. Methane consumption rate k (ng CH4 consumed g
      1 soil d-1) varied from 0.065 +/- 0.005 to 0.608 +/- 0.018. Lowest k was in 15 
      degrees C-60% moisture holding capacity (MHC)-no biochar and with 10 ppm
      chlorpyrifos. Highest k was in 35  degrees C-100% MHC-1% biochar and without (0
      ppm) chlorpyrifos. Cumulative CO2 production (ng CO2 produced g-1 soil d-1)
      varied from 446 +/- 15 to 1989 +/- 116. Both CH4 consumption and CO2 production
      peaked in the treatment of 35  degrees C-100% MHC-1% biochar. Chlorpyrifos
      inhibited CH4 consumption irrespective of treatments. Abundance of 16S rRNA of
      eubacteria (* 106 g-1 soil) varied from 2.33 +/- 0.58 to 85.67 +/- 7.00.
      Abundance of 16S rRNA genes representing Actinomycetes (* 104 g-1 soil) varied
      from 7.67 +/- 1.53 and pmoA gene (Methanotrophs) (* 105 g-1 soil) varied from
      1.23 +/- 0.59 to 34.33 +/- 6.51. Chlorpyrifos inhibited abundance of
      heterotrophic bacteria and methanotrophs but stimulated actinomycetes. Biochar
      stimulated the CH4 consumption, CO2 production and microbial abundance. Study
      highlighted that use of chlorpyrifos under climate change factors may inhibit CH4
      consumption but the use of biochar may alleviate the negative effect of the
      chlorpyrifos.

PMID- 29655157
TI  - Chromium resistance characteristics of Cr(VI) resistance genes ChrA and ChrB in
      Serratia sp. S2.
AB  - OBJECTIVE: To find an efficient chromium (VI) resistance system, with a highly
      efficient, economical, safe, and environmentally friendly chromium-removing
      strain, ChrA, ChrB, and ChrAB fragments of the chromium (VI) resistance gene in
      Serratia sp. S2 were cloned, and their prokaryotic expression vectors were
      constructed and transformed into E. coli BL21. The anti-chromium (VI) capacity
      and characteristics of engineered bacteria, role of ChrA and ChrB genes in the
      anti-chromium (VI) processes, and the mechanism of chromium metabolism, were
      explored. METHODS: The PCR technique was used to amplify ChrA, ChrB, and ChrAB
      genes from the Serratia sp. S2 genome. ChrA, ChrB, and ChrAB genes were connected
      to the prokaryotic expression vector pET-28a and transferred into E. coli BL21
      for prokaryotic expression. Cr-absorption and Cr-efflux ability of the engineered
      strains were determined. The effects of respiratory inhibitors and oxygenated
      anions on Cr-efflux of ChrA and ChrB engineered strains were explored. RESULTS:
      ChrA, ChrB, and ChrAB engineered strains were constructed successfully; there was
      no significant difference between the control strain and the ChrB engineered
      strain for Cr-metabolism (P > 0.05). Cr-absorption and Cr-efflux of ChrA and
      ChrAB engineered strains were significantly stronger than the control strain (P <
      0.05). Oxyanions (sulfate and molybdate) and inhibitors (valinomycin and CN-)
      could significantly inhibit the Cr-efflux capacities of ChrA and ChrAB engineered
      strains (P < 0.05), while NADPH could significantly promote such capacities (P <
      0.05). CONCLUSION: The Cr-transporter, encoded by ChrA gene, confer the ability
      to pump out intracellular Cr on ChrA and ChrAB engineered strains. The ChrB gene
      plays a positive regulatory role in ChrA gene regulation. The Cr-metabolism
      ability of the ChrAB engineered strain is stronger than the ChrA engineered
      strain. ChrA and ChrAB genes in the Cr-resistance system may involve a variety of
      mechanisms, such as sulfate ion channel and respiratory chain electron transfer.

PMID- 29655158
TI  - Mercury concentrations in blood, brain and muscle tissues of coastal and pelagic
      birds from northeastern Canada.
AB  - Mercury (Hg) is a toxic element which has increased in marine environments for
      more than a century, due largely to anthropogenic activities, and biomagnifies in
      food chains to harmful levels in some top predators like waterfowl and seabirds.
      We analysed total mercury (THg) concentrations in blood, brain and muscle tissue
      from healthy specimens of 13 coastal and pelagic bird species from eastern and
      northern Canada to provide a baseline on current concentrations, especially for
      brain concentrations which are highly underrepresented in the literature. We also
      examined within and among tissues relationships of THg concentrations within
      individuals. THg concentrations were generally higher in pelagic species and
      scavenging gulls, when compared to coastal waterfowl. Brain and muscle tissue had
      similar concentrations of THg in the birds examined, but both of these tissues
      had lower concentrations that those found in blood. Our results, and that of a
      previous study, suggest that body condition has a large influence on blood THg
      concentrations and should be considered when using blood as a sampling medium.
      Many of the species we examined had tissue THg above levels known to cause
      deleterious, sublethal effects in some species.

PMID- 29655159
TI  - The effects of Bisphenol A on the seagrass Cymodocea nodosa: Leaf elongation
      impairment and cytoskeleton disturbance.
AB  - Bisphenol A (BPA) is an emerging pollutant of environmental concern, classified
      as "moderately toxic" and "toxic", causing adverse effects on aquatic biota.
      Although information about BPA toxicity on aquatic fauna is available, the data
      about BPA effects on aquatic flora remain scarce, missing for marine macrophytes.
      The effects of environmentally relevant BPA concentrations (ranging from 0.03 to
      3 MUg L-1) on juvenile leaf elongation and the cytoskeleton (microtubules, MTs
      and actin filaments, AFs) were studied in the seagrass Cymodocea nodosa for 1-10
      days. The suitability of cytoskeleton disturbance and leaf elongation impairment
      as "biomarkers" for BPA stress were tested. The highest BPA concentrations (0.3,
      0.5, 1 and 3 MUg L-1) affected significantly leaf elongation from the onset of
      the experiment, while defects of the cytoskeleton were observed even at lower
      concentrations. In particular, MTs were initially disrupted (i.e. "lowest
      observed effect concentrations", LOECs) at 0.1 MUg L-1, while AFs were damaged
      even at 0.03 MUg L-1. AFs appeared thus to be more sensitive to lower BPA
      concentrations, while there was a correlation between leaf elongation impairment
      and MT defects. Thus, AF damages, MT disruption and leaf elongation impairment in
      C. nodosa, in this particular order, appear to be sensitive "biomarkers" of BPA
      stress, at the above environmentally relevant BPA concentrations.

PMID- 29655160
TI  - Ecotoxicity of phenol and cresols to aquatic organisms: A review.
AB  - With the development of industrial production and continuous demand for
      chemicals, a large volume of wastewater containing phenols was discharged into
      the aquatic environment. Moreover, chemical leakage further increased the
      emission of phenols into aquatic systems. Phenol and its methylated derivative
      (cresols) were selected due to their extensive use in industry and ecotoxicity to
      freshwater and marine organisms. This review focused on the ecotoxicity of phenol
      and m-, o-, and p-cresol on aquatic systems. The mechanism of action of phenols
      was also discussed. The aim of this literature review was to summarise the
      knowledge of the behaviour, and toxicity on marine and freshwater organisms, of
      phenols as well as to try to select a series of sensitive biomarkers suitable for
      ecotoxicological assessment and environmental monitoring in aquatic environments.

PMID- 29655161
TI  - Functional video-based analysis of 3D cardiac structures generated from human
      embryonic stem cells.
AB  - Human embryonic stem cells (hESCs) differentiated into cardiomyocytes (CM) often
      develop into complex 3D structures that are composed of various cardiac cell
      types. Conventional methods to study the electrophysiology of cardiac cells are
      patch clamp and microelectrode array (MEAs) analyses. However, these methods are
      not suitable to investigate the contractile features of 3D cardiac clusters that
      detach from the surface of the culture dishes during differentiation. To overcome
      this problem, we developed a video-based motion detection software relying on the
      optical flow by Farneback that we call cBRA (cardiac beat rate analyzer). The
      beating characteristics of the differentiated cardiac clusters were calculated
      based on the local displacement between two subsequent images. Two
      differentiation protocols, which profoundly differ in the morphology of cardiac
      clusters generated and in the expression of cardiac markers, were used and the
      resulting CM were characterized. Despite these differences, beat rates and
      beating variabilities could be reliably determined using cBRA. Likewise,
      stimulation of beta-adrenoreceptors by isoproterenol could easily be identified
      in the hESC-derived CM. Since even subtle changes in the beating features are
      detectable, this method is suitable for high throughput cardiotoxicity
      screenings.

PMID- 29655162
TI  - Knockdown of NLRC5 attenuates renal I/R injury in vitro through the activation of
      PI3K/Akt signaling pathway.
AB  - NLRC5, as the largest member of nucleotide-binding domain and leucine-rich repeat
      (NLR) family, was involved in various physiological processes, such as
      inflammation, fibrosis, innate immunity and diabetic nephropathy. However, the
      role of NLRC5 in acute kidney injury remains unclear. The aim of this study was
      to investigate the role of NLRC5 in human renal proximal tubular epithelial cells
      (HK-2) exposed to hypoxia/reoxygenation (H/R). Our results demonstrated that the
      expression of NLRC5 was significantly up-regulated in HK-2 cells exposed to H/R.
      Knockdown of NLRC5 significantly improved the viability of HK-2 cells exposed to
      H/R. In addition, knockdown of NLRC5 efficiently inhibited H/R-induced oxidative
      stress and apoptosis in HK-2 cells. Mechanistically, knockdown of NLRC5 markedly
      enhanced the activation of PIK3/Akt signaling pathway in H/R-stimulated HK-2
      cells. In summary, our findings indicate that knockdown of NLRC5 attenuates renal
      I/R injury in vitro through the activation of PI3K/Akt signaling pathway.

PMID- 29655163
TI  - Insulin specifically regulates expression of liver and muscle phosphofructokinase
      isoforms.
AB  - Phosphofructokinase (PFK) is a key regulatory enzyme of glycolysis, being
      considered the pacemaker of this pathway. In mammals, this enzyme exists as three
      different isoforms, PFKM, PFKL and PFKP, presenting different regulatory and
      catalytic properties. The expression of these isoforms is tissue-specific and
      vary according to the cell differentiation and signalization. Although it is
      known that the expression of the different PFK isoforms directly affects cell
      function, the information regarding the regulation of PFK isoforms expression is
      scarce. In the present work, we evaluate the role of insulin signalization on the
      expression of three PFK isoforms on skeletal muscle, liver, and epididymal white
      adipose tissue (eWAT) of mice. For this, Swiss mice were treated with
      streptozotocin (STZ) to disrupt pancreatic beta-cells and, thus, insulin
      production. Control group were treated with citrate buffer (STZ vehicle). These
      groups were then treated with insulin or saline twice a day for ten consecutive
      days when animals were euthanized and tissues used for the evaluation of PFK
      isoforms expression by quantitative PCR (qPCR). Our results revealed that the
      lack of insulin significantly impacted the expression of PFKL, presenting mild
      effects on PFKM and no effects on PFKP. The decrease of PFKL and PFKM mRNA levels
      observed on the group treated with STZ was reversed by the treatment with
      insulin. In conclusion, insulin, the most known regulator of glucose consumption,
      specifically regulates the expression of PFKL and PFKM, which impact the
      regulation of glycolysis in the cell.

PMID- 29655164
TI  - Bornyl acetate suppresses ox-LDL-induced attachment of THP-1 monocytes to
      endothelial cells.
AB  - Leukocyte recruitment to the surface of the endothelium plays a pivotal role in
      the development of cardiovascular diseases. Bornyl acetate is the main volatile
      constituent present in numerous conifer oils, which has displayed its anti
      oxidant and anti-inflammatory properties in different types of tissues and cells.
      However, little information regarding the effects of bornyl acetate on vascular
      endothelial inflammation has been reported before. In the current study, we aimed
      to investigate the pharmacological roles of bornyl acetate against ox-LDL-induced
      leukocyte adhesion to the endothelium. Our findings indicate that bornyl acetate
      ameliorated ox-LDL-induced reduction in cell viability of HUVECs. Additionally,
      bornyl acetate inhibited the attachment of THP-1 monocytes to HUVECs induced by
      treatment with ox-LDL through ameliorating the expression of ICAM-1, VCAM-1, and
      E-selectin. Mechanistically, we found that bornyl acetate could suppress
      activation of the IkappaBalpha/NF-kappaB signaling pathway. Lastly, our results
      indicate that bornyl acetate mitigated expression of the pro-inflammatory
      cytokines TNF-alpha and IL-1beta. Our results suggest the therapeutic potential
      of bornyl acetate in patients with atherosclerosis.

PMID- 29655165
TI  - A review of FGF signaling in palate development.
AB  - The fibroblast growth factors (FGFs) play a critical role during palatogenesis by
      mediating a variety of cellular responses. Extensive epidemiological and genetic
      studies over several decades in humans have revealed members of the FGF family
      function as candidate genes for syndromic and nonsyndromic cleft lip and cleft
      palate. The findings that FGFs signaling work delicately in the development of
      palate have been confirmed in mice carrying targeted mutations. Here we try to
      review recent progress toward a detailed understanding of FGF signaling including
      FGF7, FGF8, FGF9, FGF10, FGF18 and their receptors FGFR1, FGFR2 in palate
      development studies and discuss how they interact with other factors on the basis
      of animal studies regarding cleft palate.

PMID- 29655166
TI  - Paeoniflorin attenuates depressive behaviors in systemic lupus erythematosus
      mice.
AB  - The present study was to evaluate the effects of paeoniflorin (PA) on systemic
      lupus erythematosus induced depressive behaviors. 10 wild type mice and 20
      MRL/lpr mice were applied for the research. The animals were randomly assigned to
      wild type, MRL/lpr group and MRL/lpr + PA group. PA restored depressive-like
      behaviors, such as sucrose consumption, immobile time in the tail suspension
      tests (TST) and forced swimming tests (FST). PA significantly decreased the
      levels of interleukin-6 (IL-6), IL-1beta, tumor necrosis factor-alpha (TNF-alpha)
      in serum and hippocampus of MRL/lpr mice. Western blot results demonstrated PA
      inhibited the levels of HMGB1/TLR4/NF-kappaB pathway. The findings showed that PA
      was beneficial for the prevention of systemic lupus erythematosus induced
      depressive behaviors, which possibly by suppressing HMGB1/TLR4/NF-kappaB pathway.

PMID- 29655168
TI  - Upper body kinematic and muscular variability in response to targeted rotator
      cuff fatigue.
AB  - The rotator cuff muscles are prominent stabilizers of the shoulder and are
      vulnerable to muscle fatigue. Rotator cuff fatigue may result in subacromial
      impingement (SAI) through the superior translation of the humeral head. Scapular
      changes have been reported inconsistently, but may prevent SAI. The purpose of
      this study was to quantify changes in scapular kinematics, as well as muscle
      activity during glenohumeral motions following targeted rotator cuff fatigue. Ten
      healthy men completed four planar glenohumeral motions (cross-flexion, frontal,
      scapular, and sagittal plane elevation) prior to and immediately following a
      rotator cuff fatigue protocol on two separate days. Scapular kinematics and
      muscle activity of thirteen muscles were recorded. Scapular protraction decreased
      significantly with fatigue during scapular plane elevation (p < 0.001; etap2 =
      0.74). Although not significant, large effect sizes were found with decreased
      scapular protraction during elevation in the frontal (p = 0.012; etap2 = 0.52)
      and sagittal planes (p = 0.007; etap2 = 0.58), as well as decreased scapular
      medial rotation during cross-flexion (p = 0.008; etap2 = 0.56). Between-subject
      variability (standard deviations from 2.3 degrees  to 14.5 degrees ) and within
      subject day-to-day differences (upwards of 10 degrees  deviation in the opposite
      direction) were high among all kinematic changes following fatigue. Considerable
      day-to-day differences in scapular stabilizer muscle activity in response to
      fatigue were present. Due to the degrees of freedom at the upper extremity,
      individuals can employ a variety of compensatory strategies to fatigue. The
      variable compensatory strategies across the scapular stabilizers resulted in
      individual-specific scapular kinematic changes that could act as either
      impingement-sparing or impingement-promoting. The high variance in day-to-day
      differences within-subjects indicates that kinematic and muscular responses to
      fatigue may be adaptive within individuals over time.

PMID- 29655167
TI  - IL-8 antagonist, CXCL8(3-72)K11R/G31P coupled with probiotic exhibit variably
      enhanced therapeutic potential in ameliorating ulcerative colitis.
AB  - Inflammatory bowel disease (IBD) remains a major health challenge due in part to
      unsafe and limited treatment options, hence there is the need for alternatives.
      CXCL8/interleukin 8 (IL-8) is elevated in inflammation, and binds preferentially
      to G protein-couple receptors (GPCRs) CXCR1/2 of the CXC chemokine family to
      initiate cascades of downstream inflammatory signals. A mutant CXCL8 protein,
      CXCL8(3-72)K11R/G31P (G31P), competitively and selectively binds to CXCR1/2,
      making CXCL8 redundant. We explore the therapeutic potential of G31P in dextran
      sulfate sodium (DSS) induced ulcerative colitis (UC), and the corresponding
      effect if G31P treatment is augmented with Lactobacillus acidophilus (LACT). The
      treatment options administered significantly reduced TNF-alpha, IFN-gamma, IL
      1beta, IL-6, and IL-8, but maintained elevated levels of IL-10. CD68 and F4/80
      expressions were down-regulated and showed restricted infiltration to inflamed
      colon, while IL-17F levels were insignificantly different from the DSS treated
      mice. Also, we observed up-regulation of IL-17A in G31P + LACT but not G31P
      treated mice if compared with Control group. The treatments ameliorated colonic
      fibrosis by reducing VEGF, TGF-beta, MMP-2 and MMP-9. In addition, we observed
      elevated levels of E-cadherin, and marginal up-regulation of occludin, suggesting
      the role of the treatments in regulating tight intestinal junction and adherence
      proteins. Mechanism-wise, G31P interferes with AKT and ERK signaling pathways.
      Our study suggests that G31P confers protection in IBD, particularly UC, and when
      G31P treatment is augmented with Lactobacillus acidophilus, the protection is
      variably enhanced.

PMID- 29655169
TI  - Functional brain correlates of motor response inhibition in children with
      developmental coordination disorder and attention deficit/hyperactivity disorder.
AB  - Motor impairment is associated with developmental coordination disorder (DCD),
      and to a lesser extent with attention-deficit/hyperactivity disorder (ADHD).
      Previous functional imaging studies investigated children with DCD or ADHD only;
      however, these two disorders co-occur in up to 50% of cases, suggesting that
      similar neural correlates are associated with these disorders. This study
      compared functional brain activation in children and adolescents (age range 8-17,
      M = 11.73, SD = 2.88) with DCD (n = 9), ADHD (n = 20), co-occurring DCD and ADHD
      (n = 18) and typically developing (TD) controls (n = 20). When compared to TD
      controls, children with co-occurring DCD/ADHD showed decreased activation during
      response inhibition in primary motor and sensory cortices. These findings suggest
      that children with co-occurring DCD and ADHD display significant functional
      changes in brain activation that could interfere with inhibition of erroneous
      motor responses. In contrast to previous studies, significant alterations in
      brain activation relative to TD controls, were not found in children with
      isolated DCD or ADHD. These findings highlight the importance of considering co
      occurring disorders when investigating brain function in children with
      neurodevelopmental disorders.

PMID- 29655170
TI  - Frequency of hepatitis B surface antigen variants (HBsAg) in hepatitis B virus
      genotype B and C infected East- and Southeast Asian patients: Detection by the
      Elecsys(r) HBsAg II assay.
AB  - BACKGROUND: To avoid false negative results, hepatitis B surface antigen (HBsAg)
      assays need to detect samples with mutations in the immunodominant 'a'
      determinant region, which vary by ethnographic region. OBJECTIVE: We evaluated
      the prevalence and type of HBsAg mutations in a hepatitis B virus (HBV)-infected
      East- and Southeast Asian population, and the diagnostic performance of the
      Elecsys(r) HBsAg II Qualitative assay. STUDY DESIGN: We analyzed 898 samples from
      patients with HBV infection from four sites (China [Beijing and Guangzhou], Korea
      and Vietnam). HBsAg mutations were detected and sequenced using highly sensitive
      ultra-deep sequencing and compared between the first (amino acids 124-137) and
      second (amino acids 139-147) loops of the 'a' determinant region using the
      Elecsys(r) HBsAg II Qualitative assay. RESULTS: Overall, 237 distinct amino acid
      mutations in the major hydrophilic region were identified; mutations were present
      in 660 of 898 HBV-infected patient samples (73.5%). Within the pool of 237
      distinct mutations, the majority of the amino acid mutations were found in HBV
      genotype C (64.8%). We identified 25 previously unknown distinct mutations,
      mostly prevalent in genotype C-infected Korean patients (n = 18) followed by
      Chinese (n = 12) patients. All 898 samples were correctly identified by the
      Elecsys(r) HBsAg II Qualitative assay. CONCLUSIONS: We observed 237 distinct
      (including 25 novel) mutations, demonstrating the complexity of HBsAg variants in
      HBV-infected East- and Southeast Asian patients. The Elecsys(r) HBsAg II
      Qualitative assay can reliably detect HBV-positive samples and is suitable for
      routine diagnostic use in East and Southeast Asia.

PMID- 29655171
TI  - Alterations of network synchrony after epileptic seizures: An analysis of post
      ictal intracranial recordings in pediatric epilepsy patients.
AB  - OBJECTIVE: Post-ictal EEG alterations have been identified in studies of
      intracranial recordings, but the clinical significance of post-ictal EEG activity
      is undetermined. The purpose of this study was to examine the relationship
      between peri-ictal EEG activity, surgical outcome, and extent of seizure
      propagation in a sample of pediatric epilepsy patients. METHODS: Intracranial EEG
      recordings were obtained from 19 patients (mean age = 11.4 years, range = 3-20
      years) with 57 seizures used for analysis (mean = 3.0 seizures per patient). For
      each seizure, 3-min segments were extracted from adjacent pre-ictal and post
      ictal epochs. To compare physiology of the epileptic network between epochs, we
      calculated the relative delta power (Delta) using discrete Fourier transformation
      and constructed functional networks based on broadband connectivity (conn). We
      investigated differences between the pre-ictal (Deltapre, connpre) and post-ictal
      (Deltapost, connpost) segments in focal-network (i.e., confined to seizure onset
      zone) versus distributed-network (i.e., diffuse ictal propagation) seizures.
      RESULTS: Distributed-network (DN) seizures exhibited increased post-ictal delta
      power and global EEG connectivity compared to focal-network (FN) seizures.
      Following DN seizures, patients with seizure-free outcomes exhibited a 14.7% mean
      increase in delta power and an 8.3% mean increase in global connectivity compared
      to pre-ictal baseline, which was dramatically less than values observed among
      seizure-persistent patients (29.6% and 47.1%, respectively). SIGNIFICANCE: Post
      ictal differences between DN and FN seizures correlate with post-operative
      seizure persistence. We hypothesize that post-ictal deactivation of subcortical
      nuclei recruited during seizure propagation may account for this result while
      lending insights into mechanisms of post-operative seizure recurrence.

PMID- 29655172
TI  - Sparse-coding denoising applied to reversible conformational switching of a
      porphyrin self-assembled monolayer induced by scanning tunnelling microscopy.
AB  - Scanning tunnelling microscopy (STM) was used to induce conformational molecular
      switching on a self-assembled monolayer of zinc-octaethylporphyrin on a
      graphite/tetradecane interface at room temperature. A reversible conformational
      change controlled by applying a tip voltage was observed. Consecutive STM images
      acquired at alternating tip voltages showed that at 0.4 V the porphyrin monolayer
      presents a molecular arrangement formed by alternate rows with two different
      types of structural conformations and when the potential is increased to 0.7 V
      the monolayer presents only one type of conformation. In this paper, we
      characterize these porphyrin conformational dynamics by analyzing the STM images,
      which were improved for better quality and interpretation by means of a denoising
      algorithm, adapted to process STM images from state of the art image processing
      and analysis methods. STM remains the best technique to 'see' and to manipulate
      the matter at atomic scale. A very sharp tip a few angstroms of the surface can
      provide images of molecules and atoms with a powerful resolution. However, these
      images are strongly affected by noise which is necessary to correct and
      eliminate. This paper is about new computational tools specifically developed to
      denoise the images acquired with STM. The new algorithms were tested in STM
      images, obtained at room temperature, of porphyrin monolayer which presents
      reversible conformational change in function of the tip bias voltage. Images with
      high resolution, acquired in real time, show that the porphyrins have different
      molecular arrangements whether the tip voltage is 0.4 V or 0.7 V.

PMID- 29655173
TI  - Subclinical thyroid dysfunction and circulating thyroid hormones are not
      associated with bone turnover markers or incident hip fracture in older men.
AB  - OBJECTIVE: Overt thyroid dysfunction is a risk factor for osteoporosis and
      fractures. Subclinical hyperthyroidism has also been associated with fracture. It
      remains unclear whether variation in thyroid hormones within the euthyroid range
      modulates bone health, particularly among older men. We assessed whether thyroid
      stimulating hormone (TSH) and free thyroxine (FT4) are associated with bone
      turnover markers (BTMs) and predict hip fracture risk in community-dwelling older
      men without known thyroid disease. DESIGN: Prospective cohort study. PATIENTS:
      Four thousand two hundred forty-eight men aged 70-89 years. MEASUREMENTS:
      Baseline blood samples were assayed for TSH, FT4, total osteocalcin (TOC),
      undercarboxylated osteocalcin (ucOC), N-terminal propeptide of type I collagen
      (P1NP) and collagen type I C-terminal cross-linked telopeptide (CTX). Incidence
      of hip fracture events was ascertained to 2012. Associations of TSH and FT4 with
      BTMs were analysed at baseline using Pearson correlation coefficients, and with
      incident hip fracture using Cox proportional hazards regression. RESULTS: After
      excluding men with pre-existing thyroid or bone disease, there were 3, 338 men
      for analysis. Of these, 3, 117 were euthyroid, 135 had subclinical
      hypothyroidism, and 86 had subclinical hyperthyroidism. Men with subclinical
      thyroid disease were older, and those with subclinical hyperthyroidism had lower
      creatinine than the other groups. After multivariate analysis, there were no
      associations found between FT4, TSH or subclinical thyroid dysfunction and BTMs
      at baseline. Neither subclinical thyroid dysfunction, TSH nor FT4 were predictive
      of incident hip fracture in our study population. CONCLUSIONS: In euthyroid older
      men, TSH and FT4 were not associated with BTMs or incident hip fracture. Our
      findings differ from those previously described in postmenopausal women.

PMID- 29655174
TI  - Guard cells in fern stomata are connected by plasmodesmata, but control cytosolic
      Ca2+ levels autonomously.
AB  - Recent studies have revealed that some responses of fern stomata to environmental
      signals differ from those of their relatives in seed plants. However, it is
      unknown whether the biophysical properties of guard cells differ fundamentally
      between species of both clades. Intracellular micro-electrodes and the
      fluorescent Ca2+ reporter FURA2 were used to study voltage-dependent cation
      channels and Ca2+ signals in guard cells of the ferns Polypodium vulgare and
      Asplenium scolopendrium. Voltage clamp experiments with fern guard cells revealed
      similar properties of voltage-dependent K+ channels as found in seed plants.
      However, fluorescent dyes moved within the fern stomata, from one guard cell to
      the other, which does not occur in most seed plants. Despite the presence of
      plasmodesmata, which interconnect fern guard cells, Ca2+ signals could be
      elicited in each of the cells individually. Based on the common properties of
      voltage-dependent channels in ferns and seed plants, it is likely that these key
      transport proteins are conserved in vascular plants. However, the symplastic
      connections between fern guard cells in mature stomata indicate that the
      biophysical mechanisms that control stomatal movements differ between ferns and
      seed plants.

PMID- 29655175
TI  - Efficacy and dermal tolerance of a novel alcohol-based skin antiseptic in horses.
AB  - OBJECTIVE: To determine the efficacy and dermal tolerance of a novel alcohol
      based skin antiseptic (ABSA) in horses. STUDY DESIGN: Experimental study. ANIMAL
      POPULATION: Systemically healthy horses (n = 25) with no history or clinical
      signs of skin disease. METHODS: Four clipped sites on the abdomen were randomly
      assigned to a skin preparation protocol: saline (negative control; NC),
      chlorhexidine gluconate followed by isopropyl alcohol (positive control; PC),
      saline followed by the ABSA (ABSA A), or a commercially available horse shampoo
      followed by the ABSA (ABSA B). Microbiological swabs were obtained from each site
      and cultured on MacConkey and mannitol salt agar plates. Colony-forming units
      were counted 18-24 hours later. All sites were scored for signs of skin reaction
      before, immediately after, 1 hour after, and 24 hours after skin preparation.
      RESULTS: The PC, ABSA A, and ABSA B methods reduced skin microbial burden
      compared with the NC method (P < .001), but no difference was detected between
      antiseptic products. Preparation time did not differ between ABSA A and ABSA B
      methods (P = 0.108); both were faster than the PC method (P < 0.001 for both).
      Skin reactions were most abundant 24 hours after skin preparation (30.5%), but
      there was no significant association with antiseptic used, and no horses required
      veterinary treatment. CONCLUSION: The ABSA preparations tested in this study were
      as effective and well tolerated as a chlorhexidine gluconate-based method, but
      required less time in healthy horses. CLINICAL SIGNIFICANCE: The ABSA tested here
      provides an efficacious, fast-acting, and well-tolerated alternative to achieve
      skin antisepsis in healthy horses. These results justify further investigation in
      clinical cases.

PMID- 29655176
TI  - Growth Hormone Secretagogue (A233) Improves Growth and Changes the Tissue Fatty
      Acid Profile in Juvenile Tilapia (Oreochromis niloticus).
AB  - Growth hormone (GH) release is a process that is well regulated by several
      factors, including GH secretagogues. GH can mediate the regulation of the fatty
      acid level and composition. The aim of this study was to determine the effect of
      a synthetic GH secretagogue peptide (A233) on the growth and fatty acid
      composition in tilapia (Oreochromis niloticus). To address this objective, we
      administrated a diet supplemented with A233 to juvenile tilapia for 60 days. The
      group fed with a diet supplemented with 600 MUg of A233 per kg of feed increased
      in weight (4.81 +/- 0.09 g) and specific growth rate (2.49 +/- 0.03%/day)
      compared to the control diet group (3.63 +/- 0.08 g, 2.07 +/- 0.04%/day;
      respectively) (p < 0.001). In the muscle, the total lipids for the control diet
      group were higher than that in the group fed with 600 MUg of A233 per kg feed;
      however, no differences were detected in the liver. In both tissues, the patterns
      of fatty acid composition and content were generally similar, with some
      exceptions. Tilapia fed with 600 MUg of A233 per kg of feed showed, in liver and
      muscle, a significantly higher composition and content of n-3 polyunsaturated
      fatty acids (such as 20:5n-3, 22:5n-3, 22:6n-3) and n-3/n-6 PUFA than animals fed
      with the control diet. To our knowledge, this is the first report on the the
      effects of natural or synthetic GH secretagogues (GHS) on fatty acid composition,
      implying an increase in the nutritional quality of the tilapia.

PMID- 29655177
TI  - Successful treatment with interleukin-17A antagonists of generalized pustular
      psoriasis in patients without IL36RN mutations.
AB  - Generalized pustular psoriasis (GPP) is a potentially life-threatening disease
      that can be attributed to mutations in IL36RN in a subgroup of patients. In small
      trials, interleukin (IL)-17A and IL-17RA antagonists have been shown to be
      effective in patients with generalized pustular psoriasis in Japan. We identified
      seven patients who received the IL-17A antagonists secukinumab (six cases) or
      ixekizumab (one case) in two dermatological centers. All patients showed a good
      or excellent clinical response. Anti-IL-17A therapy was well tolerated and
      ongoing in all patients after an average therapy duration of 12.9 months.
      Analysis of IL36RN mutation status was performed in six patients, one patient
      carried a heterozygous mutation, while the other five patients did not show a
      mutation in IL36RN. This is the first report of a successful treatment of GPP
      patients without IL36RN mutations responding to anti-IL-17A therapy.

PMID- 29655178
TI  - Screening of candidate biomaterials for alveolar augmentation using a critical
      size rat calvaria defect model.
AB  - OBJECTIVE: To screen candidate biomaterials intended for alveolar augmentation
      relative to their potential to enhance local bone formation using a routine
      critical-size (o8-mm) rat calvaria defect model. METHODS: One hundred and forty
      male Sprague Dawley outbred rats, age 11-12 weeks, weight 325-375 g, obtained
      from USDA approved breeder, randomised into 14 groups of 10 animals, each
      received one of the following treatments: sham-surgery (empty control), Bio-Oss
      (bovine HA/reference control), or candidate biomaterials including bovine HA,
      synthetic HA/beta-TCP and calcium phosphate constructs, mineralised/demineralised
      human bone preparations, a beta-TCP/calcium sulphate and an HA/calcium sulphate
      putty. A 4-week healing interval was chosen to discern local bone formation using
      incandescent and polarised light microscopy. Statistical analysis used one-way
      ANOVA followed by Bonferroni for pairwise comparisons. RESULTS: Candidate
      biomaterials all displayed biocompatibility. They exhibited limited, if any,
      appreciable bioerosion or biodegradation. No statistically significant
      differences in mean linear defect closure were observed among experimental
      groups, sham-surgery displaying the highest score (48.1 +/- 24.3%). Sham-surgery
      also showed a significantly greater bone area fraction than all other groups
      (19.8 +/- 13.9%, p < .001). The HA/calcium sulphate putty showed a significantly
      greater residual biomaterial area fraction than all other groups (61.1 +/- 8.5%,
      p < .01). CONCLUSION: Within the limitations of this animal model, although
      biocompatible, none of the tested biomaterials enhanced local bone formation
      beyond the innate regenerative potential of this craniotomy defect.

PMID- 29655179
TI  - Explaining European fungal fruiting phenology with climate variability.
AB  - Here we assess the impact of geographically dependent (latitude, longitude, and
      altitude) changes in bioclimatic (temperature, precipitation, and primary
      productivity) variability on fungal fruiting phenology across Europe. Two main
      nutritional guilds of fungi, saprotrophic and ectomycorrhizal, were further
      separated into spring and autumn fruiters. We used a path analysis to investigate
      how biogeographic patterns in fungal fruiting phenology coincided with seasonal
      changes in climate and primary production. Across central to northern Europe,
      mean fruiting varied by approximately 25 d, primarily with latitude. Altitude
      affected fruiting by up to 30 d, with spring delays and autumnal accelerations.
      Fruiting was as much explained by the effects of bioclimatic variability as by
      their large-scale spatial patterns. Temperature drove fruiting of autumnal
      ectomycorrhizal and saprotrophic groups as well as spring saprotrophic groups,
      while primary production and precipitation were major drivers for spring-fruiting
      ectomycorrhizal fungi. Species-specific phenology predictors were not stable,
      instead deviating from the overall mean. There is significant likelihood that
      further climatic change, especially in temperature, will impact fungal phenology
      patterns at large spatial scales. The ecological implications are diverse,
      potentially affecting food webs (asynchrony), nutrient cycling and the timing of
      nutrient availability in ecosystems.

PMID- 29655180
TI  - An outbreak due to Candida auris with prolonged colonisation and candidaemia in a
      tertiary care European hospital.
AB  - Multidrug-resistant Candida auris has emerged as a cause of insidious hospital
      outbreaks and complicated infections. We present the analysis of an ongoing C.
      auris outbreak including the largest published series of C. auris bloodstream
      infection. All C. auris-positive patients from April-2016 to January-2017 were
      included. Environmental, clinical and microbiological data were recorded.
      Definitive isolate identification was performed by ITS-rDNA sequencing, and
      typing by amplified fragment length polymorphism fingerprinting. One hundred and
      forty patients were colonised by C. auris during the studied period (68% from
      surgical intensive care). Although control measures were implemented, we were not
      able to control the outbreak. Forty-one invasive bloodstream infections (87.8%
      from surgical intensive care) were included. Clinical management included prompt
      intravascular catheter removal and antifungal therapy with echinocandins. All
      isolates were fluconazole- and voriconazole-resistant, but echinocandin- and
      amphotericin B-susceptible. Thirty-day mortality rate was 41.4%, and severe
      septic metastasis as spondylodiscitis and endocarditis were observed in 5
      patients (12%). C. auris was also recovered from inanimate patient surroundings
      and medical equipment. Despite antifungal treatment, high mortality and late
      complication rates were recorded. Molecular typing suggested a clonal outbreak
      different from those previously published.

PMID- 29655182
TI  - Acquiring High-Performance Deep-Blue OLED Emitters through an Unexpected
      Blueshift Color-Tuning Effect Induced by Electron-Donating -OMe Substituents.
AB  - A series of blue-emissive 7-(diphenylamino)-4-phenoxycoumarin derivatives bearing
      -CF3 , -OMe, or -N(Me)2 substituents on the phenoxy subunit were synthesized.
      Although both the -CF3 and -N(Me)2 modifications were found to trigger redshifted
      fluorescence, the -OMe substitution was demonstrated to exert an unexpected
      blueshift color-tuning effect toward the deep-blue region. The reason is that the
      moderate electron-donating -OMe group can endow coumarins with unaltered HOMO but
      elevated LUMO energy levels. Moreover, the -OMe substitution was found to be
      beneficial to the thermal stability of these coumarins. Therefore, the trimethoxy
      substituted objective compound can act as a high-performance deep-blue organic
      light-emitting diode (OLED) emitter, and OLED based on it emits deep-blue light
      with CIE coordinates of (0.148, 0.084), maximum luminance of 7800 cd m-2 , and
      maximum external quantum efficiency of 5.1 %. These results not only shed light
      on the molecular design strategy for high-performance deep-blue OLED emitters
      through color-tuning, but also show the perspective of coumarin derivatives as
      deep-blue OLED emitters.

PMID- 29655181
TI  - Bone marrow - mesenchymal stem cells impact on the U937 cells in the presence of
      staphylococcal enterotoxin B (SEB).
AB  - The growing resistance against conventional chemotherapy in acute myeloid
      leukemia (AML) is a noticeable clinical concern. Therefore, many researchers are
      looking for novel substances to overcome drug resistance in cancer.
      Staphylococcal enterotoxin B (SEB) is a superantigen (SAg) and a promising
      compound which has lethal effects on malignant cells. In this unprecedented
      study, SEB was used against U937 cells in a co-culture system in the presence of
      human bone marrow-mesenchymal stem cells (hBM-MSCs). The effects of hBM-MSCs on
      the proliferation and survival of U937 cell line with SEB was assessed using MTT
      assay and AnnexinV/PI flowcytometry, respectively. Moreover, the expression of IL
      6, IL-10, TGF-beta, and inhibitor of nuclear factor kappa-B kinase (IKKb) was
      evaluated by real-time PCR technique. The same experiments were also carried out
      using hBM-MSCs-conditioned medium (hBM-MSCs-CM). The results showed that SEB
      reduced the proliferation and survival of U937 cell line, but hBM-MSCs or hBM
      MSCs-CM suppressed the effects of SEB. Furthermore, real-timePCR demonstrated
      that SEB could decrease the expression of IL-6, IL-10, and TGF-beta in hBM-MSCs
      (P < .05), while the production of IKKb was increased in comparison with the
      control group. These findings help us to have a broader understanding ofthe usage
      of SEB in the treatment of haematological malignancies, especially if it is
      targeted against hBM-MSCs to disrupt their supportive effects on malignant cells.

PMID- 29655183
TI  - Social media: Why AASLD and its members must lead the conversation.

PMID- 29655184
TI  - Is gender important? Victimisation and perpetration of intimate partner violence
      in mainland China.
AB  - Establishing the prevalence of intimate partner violence (IPV) has been
      recommended by International Conventions and Declarations for some time beginning
      with the Convention on the Elimination of All Forms of Discrimination against
      Women (CEDAW Articles 12 and 19) in 1979. One important recommendation of such
      international protocols is the implementation of national population prevalence
      surveys to establishing IPV as a serious social issue globally, which is intended
      to provide data for planning effective responses within signatory countries.
      However, not all countries have undertaken national prevalence surveys meaning
      that there are gaps in our understanding of who are the perpetrators and victims
      of IPV in different cultural contexts. This article presents the results of a
      scoping review of literature examining gender differences in prevalence rates of
      victimisation and perpetration of IPV in mainland China (hereon China). There has
      been little written about the prevalence of IPV in China generally, and this
      scoping process located only nine peer-reviewed articles written in both English-
      and Chinese-language journals focusing on both gender and IPV published between
      1997 and 2016. Results of this scoping review demonstrate that while both women
      and men perpetrate IPV in China, the prevalence rates of different types of IPV
      reflect gender differences in both perpetration and victimisation, suggesting
      that IPV is not a unitary phenomenon. The paper concludes by discussing the
      implications of the findings including the importance of increasing awareness of
      IPV in China more generally and developing gender-specific interventions to
      directly address different types of IPV. Directions for future research are also
      canvassed.

PMID- 29655185
TI  - Substitution-Inert Polynuclear Platinum Complexes as Metalloshielding Agents for
      Heparan Sulfate.
AB  - Cleavage of heparan sulfate proteoglycans (HSPGs) by the enzyme heparanase
      modulates tumour-related events including angiogenesis, cell invasion, and
      metastasis. Metalloshielding of heparan sulfate (HS) by positively charged
      polynuclear platinum complexes (PPCs) effectively inhibits physiologically
      critical HS functions. Studies using bacterial P. heparinus heparinase II showed
      that a library of Pt complexes varying in charge and nuclearity and the presence
      or absence of a dangling amine inhibits the cleavage activity of the enzyme on
      the synthetic pentasaccharide, Fondaparinux (FPX). Charge-dependent affinity of
      PPC for FPX was seen in competition assays with methylene blue and ethidium
      bromide. The dissociation constant (Kd ) of TriplatinNC for FPX was directly
      measured by isothermal titration calorimetry (ITC). The trend in DFT calculated
      interaction energies with heparin fragments is consistent with the spectroscopic
      studies. Competitive inhibition of TAMRA-R9 internalization in human carcinoma
      (HCT116) cells along with studies in HCT116, wildtype CHO and mutant CHO-pgsA745
      (lacking HS/CS) cells confirm that HSPG-mediated interactions play an important
      role in the cellular accumulation of PPCs.

PMID- 29655186
TI  - Lead-lead interaction: Interaction with an abandoned implantable cardiac
      defibrillator externalized lead.

PMID- 29655187
TI  - Classifying medical histories in US Medicare beneficiaries using fixed vs all
      available look-back approaches.
AB  - PURPOSE: Evaluate use of fixed and all-available look-backs to identify
      eligibility criteria and confounders among Medicare beneficiaries. METHODS: We
      identified outpatient visits (2007-2012) with recently documented (<=180 days)
      cardiovascular risk and classified patients according to whether the exposure
      (statin) was initiated within 14 days. We selected each beneficiary's first
      eligible visit (in each treatment group) that met criteria during the respective
      look-backs: continuous enrollment (1 or 3 years for fixed look-back; 180 days for
      all-available), no cancer history, and no statin claims. We estimated crude and
      standardized mortality ratio weighted hazard ratios (HRs) for the effect of
      statin initiation on incident 6-month cancer (a known null effect) and 2-year
      mortality, separately, adjusting for covariates assessed by using each look-back.
      RESULTS: Analyzing short-term cancer, the estimated HR from the all-available
      approach (HR = 0.90, 95% CI: 0.83, 0.98) was less biased than the 1-year look
      back (HR = 0.79, 95% CI: 0.73, 0.84), which included beneficiaries with prevalent
      cancer. The 3-year look-back (HR = 1.05, 95% CI: 0.90, 1.21) was somewhat less
      biased than the all-available estimate but less precise due the exclusion of a
      large proportion of observations without sufficient continuous enrollment (62.0%
      and 59.9% of initiators and non-initiators, respectively). All approaches
      produced similar estimates of the effect on all-cause mortality. Alternative look
      backs did not differ in their ability to control confounding. CONCLUSIONS: The
      all-available look-back performed nearly as well as the 3-year fixed, which
      produced the least biased point estimate. If 3-year look-backs are infeasible
      (eg, due to power/sample), all-available look-backs may be preferable to short (1
      year) fixed look-backs.

PMID- 29655188
TI  - Efficacy and safety of human chorionic gonadotropin for treatment of
      cryptorchidism: A meta-analysis of randomised controlled trials.
AB  - AIM: Although human chorionic gonadotropin (hCG) has long been employed in the
      management of cryptorchidism, its safety and efficacy is still controversial.
      Hence, in the present study, we conducted a meta-analysis of the treatment of
      cryptorchidism using hCG. METHODS: We searched the Medline, Embase, CINAHL,
      EBSCO, The Cochrane Library, China National Knowledge Infrastructure and WanFang
      databases. Data were extracted by two reviewers using the designed extraction
      form. Data up to July 2015 were obtained using the terms 'cryptorchidism',
      'chorionic gonadotropin' and 'randomised controlled trials'. All the publications
      were downloaded, and the respective authors were contacted for any further
      details and clarifications, if deemed necessary. The data analysis included
      randomised controlled trials that compared hCG with other hormone treatments
      offered to prepubescent males presenting with cryptorchidism. Testicular descent
      rate was used as the final positive outcome of the treatments offered. The
      software Review Manager (RevMan 5.3, The Cochrane Collaboration, London, UK) was
      used to review the management and data analysis. Risk ratios (RRs) with 95%
      confidence intervals (CIs) were pooled with a fixed effect model if no
      heterogeneity was present. RESULTS: A total of seven trials satisfied the
      selection criteria. The overall quality of the studies downloaded from various
      databases was low. Data from these seven studies were divided into three
      subgroups depending on the design of the trials: Two studies compared hCG with a
      placebo, and three studies compared hCG with gonadotropin-releasing hormone
      (GnRH) in unilateral cryptorchidism, whereas two other studies compared hCG with
      GnRH in bilateral cryptorchidism. Analysis of these trials revealed no
      significant differences between the effectiveness of hCG treatment and GnRH
      treatment in bilateral (RR 0.05, 95% CI (-0.29-0.40), two trials, n = 104, P =
      0.76) as well as unilateral cryptorchidism (RR 0.04, 95% CI (-0.12, 0.21), three
      trials, n = 81, P = 0.61). A meta-analysis of these studies showed that hCG
      treatment is not superior to placebo (RR 7.74, 95% CI (0.14-425.72), two trials,
      n = 31, P = 0.32). CONCLUSION: A meta-analysis of the seven studies led us to
      conclude that hCG treatment is no more effective than placebo, and there were no
      significant differences in the effectiveness of hCG versus GnRH treatment.

PMID- 29655189
TI  - Highly Tunable Heterojunctions from Multimetallic Sulfide Nanoparticles and
      Silver Nanowires.
AB  - A facile and general strategy is presented to create well-defined heterojunctions
      with ultra-small multimetallic sulfide nanoparticles (MMSNPs) uniformly coated on
      sliver nanowires. A unique aspect of this method is the atomic-level pre
      integration of multimetallic components by exploiting recently developed
      supertetrahedral metal sulfide nanoclusters. The use of such nanoclusters also
      enables the convenient formation of the ultrathin interfacial Ag2 S layer via
      etching. The heterojunctions (denoted as MMSNPs/Ag2 S/Ag-NWs) benefit from
      adjustable multimetallic components and display tunable visible-light-driven
      photocatalytic performance owing to the synergistic effect of multimetallic
      components from MMSNPs and the high carrier mobility of Ag-NWs. The synthetic
      strategy opens new routes to designing and fabricating various heterojunctions
      with multimetallic components, which could further expand their applications in
      catalysis, electronics, and photonics.

PMID- 29655190
TI  - Lichen striatus following scarlet fever in a 3-year-old female patient.

PMID- 29655192
TI  - Treatment of hallux deformities in adolescents with cerebral palsy.

PMID- 29655191
TI  - Turning Off Transcription with Bacterial RNA Polymerase through CuAAC Click
      Reactions of DNA Containing 5-Ethynyluracil.
AB  - Copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) click reaction in the
      major groove of DNA containing 5-ethynyluracil (UE ) with azides was used for
      turning off sequence-specific protein-DNA interactions. The concept was first
      demonstrated on switching off cleavage of short modified DNA by restriction
      endonuclease BamHI-HF. Finally, DNA template containing UE was used for in vitro
      transcription with E. coli RNA polymerase and the transcription was turned off by
      CuAAC with 3-azidopropane-1,2-diol or 3-azido-7-hydroxycoumarin.

PMID- 29655193
TI  - Collaboration as a process and an outcome: Consumer experiences of collaborating
      with nurses in care planning in an acute inpatient mental health unit.
AB  - This qualitative study explores inpatient mental health consumer perceptions of
      how collaborative care planning with mental health nurses impacts personal
      recovery. Semi-structured interviews were conducted with consumers close to
      discharge from one unit in Sydney, Australia. The unit had been undertaking a
      collaborative care planning project which encouraged nurses to use care plan
      documentation to promote person-centred and goal-focussed interactions and the
      development of meaningful strategies to aid consumer recovery. The interviews
      explored consumer understandings of the collaborative care planning process,
      perceptions of the utility of the care plan document and the process of
      collaborating with the nurses, and their perception of the impact of
      collaboration on their recovery. Findings are presented under four organizing
      themes: the process of collaborating, the purpose of collaborating, the nurse as
      collaborator and the role of collaboration in wider care and recovery. Consumers
      highlighted the importance of the process of developing their care plan with a
      nurse as being as helpful for recovery as the goals and strategies themselves.
      The findings provide insights into consumers' experiences of care planning in an
      acute inpatient unit, the components of care that support recovery and highlight
      specific areas for mental health nursing practice improvement in collaboration.

PMID- 29655194
TI  - Acute generalized exanthematous pustulosis induced by oxacillin confirmed by
      patch testing.

PMID- 29655195
TI  - Assessment of brain activity during voluntary anal sphincter contraction:
      Comparative study in women with and without fecal incontinence.
AB  - BACKGROUND: Voluntary anal sphincter function is driven by an extended network of
      brain structures, most of which are still unknown. Disturbances in this function
      may cause fecal incontinence. The aim of this study was to characterize the
      cerebral areas involved in voluntary contraction of the anorectal sphincter in
      healthy women and in a group of patients with fecal incontinence by using a
      standardized functional magnetic resonance imaging (fMRI) protocol. METHODS: This
      comparative study included 12 healthy women (mean age 53.17 +/- 4.93 years) and
      12 women with fecal incontinence (56.25 +/- 6.94 years). An MRI-compatible anal
      manometer was used to register voluntary external anal sphincter contraction.
      During brain fMRI imaging, participants were cued to perform 10-s series of self
      paced anal sphincter contractions at an approximate rate of 1 Hz. Brain
      structures linked to anal sphincter contractions were mapped and the findings
      were compared between the 2 study groups. KEY RESULTS: There were no differences
      in the evoked brain activity between the 2 groups. In healthy women, group fMRI
      analysis revealed significant activations in medial primary motor cortices,
      supplementary motor area, bilateral putamen, and cerebellum, as well as in the
      supramarginal gyrus and visual areas. In patients with fecal incontinence, the
      activation pattern involved similar regions without significant differences with
      healthy women. CONCLUSIONS & INFERENCES: This brain fMRI-anorectal protocol was
      able to map the brain regions linked to voluntary anal sphincter function in
      healthy and women with fecal incontinence.

PMID- 29655196
TI  - Contribution of Helicobacter pylori infection to the risk of peptic ulcer
      bleeding in patients on nonsteroidal anti-inflammatory drugs, antiplatelet
      agents, anticoagulants, corticosteroids and selective serotonin reuptake
      inhibitors.
AB  - BACKGROUND: Nonsteroidal anti-inflammatory drugs, low-dose aspirin, non-aspirin
      antiplatelet agents, anticoagulants, selective serotonin reuptake inhibitors and
      corticosteroids increase the risk of gastroduodenal bleeding. AIM: To determine
      in a retrospective cohort study the contribution of Helicobacter pylori infection
      to the risk of peptic ulcer bleeding in patients taking these drugs. METHODS:
      Among patients with peptic ulcer disease diagnosed by endoscopy from 01/2004 to
      12/2014 (N = 1719, 60% males, age 65.8 +/- 14.5), 56.9% had peptic ulcer bleeding
      (cases) and 43.1% uncomplicated peptic ulcer disease (controls). Demographics,
      intake of nonsteroidal anti-inflammatory drugs, aspirin, non-aspirin antiplatelet
      agents, anticoagulants, selective serotonin reuptake inhibitors, proton pump
      inhibitors and corticosteroids were documented. H. pylori status was determined
      by histology, rapid urease test or serology. Adjusted odds ratios (OR) were
      estimated by logistic regression analysis. RESULTS: Helicobacter pylori infection
      increased the risk of peptic ulcer bleeding in nonsteroidal anti-inflammatory
      drug and aspirin users (OR = 2.91, 95% CI = 1.71-4.98 and OR = 2.23, 95% CI =
      1.52-3.28, respectively), but not in patients on anticoagulants, selective
      serotonin reuptake inhibitor or corticosteroid therapy. H. pylori-positive status
      substantially increased the risk of peptic ulcer bleeding in patients on non
      aspirin antiplatelet agents (OR = 4.37, 95% CI = 1.28-14.99), concomitant
      aspirin/nonsteroidal anti-inflammatory drug intake (OR = 5.85, 95% CI = 1.68
      20.36) and combined antiplatelet therapy (OR = 8.43, 95% CI = 1.09-65.17). After
      further adjustment for proton pump inhibitor intake, H. pylori infection was
      still a risk factor for peptic ulcer bleeding in nonsteroidal anti-inflammatory
      drug and aspirin users. CONCLUSIONS: Helicobacter pylori infection increases the
      risk of peptic ulcer bleeding in peptic ulcer disease patients on nonsteroidal
      anti-inflammatory drugs, aspirin and non-aspirin antiplatelet agents. H. pylori
      positive patients on combined antiplatelet therapy carry the highest risk for
      peptic ulcer bleeding.

PMID- 29655197
TI  - High-Temperature Particulate Matter Filtration with Resilient Yttria-Stabilized
      ZrO2 Nanofiber Sponge.
AB  - Particulate matter (PM) is a major air pollutant in many regions, jeopardizing
      ecosystems and public health. Filtration at pollutant source is one of the most
      important ways to protect the environment, however, considering the high
      temperature exhaust gas emissions, effective removal of PM and related pollutants
      from their sources remains a major challenge. In this study, a resilient, heat
      resisting, and high-efficiency PM filter based on yttria-stabilized ZrO2 (YSZ)
      nanofiber sponge produced with a scalable solution blow spinning process is
      reported. The porous 3D sponge composed of YSZ nanofibers is lightweight (density
      of 20 mg cm-3 ) and resilient at both room temperature and high temperatures. At
      room-temperature conditions, the YSZ nanofiber sponge exhibits 99.4% filtration
      efficiency for aerosol particles with size in the range of 20-600 nm, associated
      with a low pressure drop of only 57 Pa under an airflow velocity of 4.8 cm s-1 .
      At a high temperature of 750  degrees C, the ceramic sponge maintains a high
      filtration efficiency of 99.97% for PM0.3-2.5 under a high airflow velocity of 10
      cm s-1 . A practical vehicle exhaust filter to capture particles with filtration
      efficiency of >98.3% is also assembled. Hence, the YSZ nanofiber sponge has
      enormous potential to be applied in industry.

PMID- 29655199
TI  - Transition from hospital to outpatient diabetes care.

PMID- 29655198
TI  - Combination TS-1 plus EGFR-tyrosine kinase inhibitors (TKIs) for the treatment of
      non-small cell lung cancer after progression on first-line or further EGFR-TKIs:
      A phase II, single-arm trial.
AB  - BACKGROUND: EGFR-tyrosine kinase inhibitors (TKIs) combined with TS-1 might
      overcome EGFR-TKI resistance, which has been indicated by several preclinical
      studies. We investigated the synergistic efficacy and safety of the combination
      therapy of EGFR-TKIs and TS-1 in non-small cell lung cancer (NSCLC) patients with
      acquired resistance to previous EGFR-TKI therapy. METHODS: This was a phase II,
      single-arm and single-center prospective study. Stage IIIB-IV NSCLC patients with
      acquired resistance to prior EGFR-TKI treatment were enrolled. All patients were
      administered combination therapy of TS-1 and continuing EGFR-TKIs in this study.
      The primary endpoints were progression-free survival (PFS), while overall
      survival (OS), disease control rate (DCR), and safety were secondary endpoints.
      RESULTS: A total of 42 patients with acquired resistance to EGFR-TKIs were
      eligible for this study. The median PFS for all patients was five months (95%
      confidence interval [CI] 3.6-5.4). The OS and DCR were 31.9 (95% CI 17.8-46.0)
      months and 69.0% (29/42), respectively. No grade 4 toxicity or grade 3
      hematologic toxicity was observed in this study. One patient (2%) experienced
      grade 3 elevated total serum bilirubin. CONCLUSION: The combination treatment of
      TS-1 and EGFR-TKIs was effective and well tolerated by patients who had
      experienced prior EGFR-TKI treatment failure. Our results need to be validated by
      larger prospective clinical trials.

PMID- 29655200
TI  - Infant formula feeding practices associated with rapid weight gain: A systematic
      review.
AB  - Excess or rapid weight gain during the first 2 years of life is associated with
      an increased risk of later childhood and adult overweight and obesity. When
      compared with breastfed infants, formula fed infants are more likely to
      experience excess or rapid weight gain, and this increased risk in formula fed
      infant populations may be due to a number of different mechanisms. These
      mechanisms include the nutrient composition of the formula and the way formula is
      prepared and provided to infants. This systematic literature review examines the
      association between formula feeding practice and excess or rapid weight gain.
      This review explores these different mechanisms and provides practical
      recommendations for best practice formula feeding to reduce rapid weight gain.
      Eighteen studies are included in this review. The findings are complicated by the
      challenges in study design and accuracy of measurements. Nevertheless, there are
      some potential recommendations for best practice formula feeding that may reduce
      excess or rapid weight gain, such as providing formula with lower protein
      content, not adding cereals into bottles, not putting a baby to bed with a
      bottle, and not overfeeding formula. Although further well designed studies are
      required before more firm recommendations can be made.

PMID- 29655201
TI  - Improving classical scoring functions using random forest: The non-additivity of
      free energy terms' contributions in binding.
AB  - Despite recent efforts to improve the scoring performance of scoring functions,
      accurately predicting the binding affinity is still a challenging task.
      Therefore, different approaches were tried to improve the prediction performance
      of four scoring functions (x-score, vina, autodock, and rf-score) by substituting
      the linear regression model of classical scoring function by random forest to
      examine the performance improvement if an additive functional form is not
      imposed, and by combining different scoring functions into hybrid ones. The
      datasets were derived from the PDBbind-CN database version 2016. When evaluating
      the original scoring functions on the generic dataset, rf-score has outperformed
      classical scoring functions, which shows the superiority of descriptor-based
      scoring functions. Substituting linear regression as a linear model by random
      forest as a nonlinear model had largely improved the scoring performance of
      autodock and vina while x-score had only a slight performance increase. All
      hybrid scoring functions had only a slight improvement-if any-on both of the
      combined scoring functions, which is not worth the slower calculation time.

PMID- 29655202
TI  - Development of a body condition score for the mountain chicken frog
      (Leptodactylus fallax).
AB  - The Critically Endangered mountain chicken frog (Leptodactylus fallax) has
      undergone drastic population decline due to habitat loss, hunting, invasive
      species, and chytridiomycosis. In response, several partner institutions
      initiated a conservation breeding program. It is important to maintain the
      captive population in good health. Therefore the program partners have
      recommended establishment of protocols for health examination of the species,
      including body condition assessment. Visual body condition scoring is a useful
      means to assess body condition in zoo animals for which regular bodyweight
      measurements are impractical or associated with capture-related stress. In this
      study, the authors developed a visual body condition score for the mountain
      chicken frog based on an ordinal categorical scale from 1 to 5 (1 = lowest body
      condition, 5 = highest body condition) using anatomical features that vary with
      total body energy reserves. Veterinary staff, animal managers, keepers,
      researchers, and students subsequently used the body condition score to assign
      scores to 98 mountain chicken frogs (41 male, 57 female) aged between 8 months
      and 12 years housed in five zoos in the UK and Jersey between February and March
      2016. Body condition scores showed moderate (rho = 0.54; males) to strong (rho =
      0.6; females) correlation with the scaled mass index, an objective measure of
      total energy reserves. The majority of pairwise comparisons between scores showed
      slight to substantial intra-observer agreement (93.8%) and slight to almost
      perfect inter-observer agreement (97.2%). Cases of poor agreement were likely due
      to limited observer experience working with the species.

PMID- 29655203
TI  - Diagnostic outcomes for genetic testing of 70 genes in 8565 patients with
      epilepsy and neurodevelopmental disorders.
AB  - OBJECTIVE: We evaluated >8500 consecutive, unselected patients with epilepsy and
      neurodevelopmental disorders who underwent multigene panel testing to determine
      the average age at molecular diagnosis and diagnostic yield of 70 genes. METHODS:
      We reviewed molecular test results for 70 genes known to cause epilepsy and
      neurodevelopmental disorders using next generation sequencing (NGS) and exon
      level array comparative genomic hybridization (aCGH). A positive result was
      defined as the presence of 1 or 2 pathogenic or likely pathogenic (P/LP) variants
      in a single gene, depending on the mode of inheritance of the associated
      disorder. RESULTS: Overall, 22 genes were found to have a high yield of positive
      findings by genetic testing, with SCN1A and KCNQ2 accounting for the greatest
      number of positive findings. In contrast, there were no positive findings in 16
      genes. Most of the P/LP variants were sequence changes identified by NGS (90.9%),
      whereas ~9% were gross deletions or duplications detected by exon-level aCGH. The
      mean age of molecular diagnosis for the cohort was 5 years, 8 months (ranging
      from 1 week to 47 years). Recurrent P/LP variants were observed in 14 distinct
      genes, most commonly in MECP2, KCNQ2, SCN1A, SCN2A, STXBP1, and PRRT2. Parental
      testing was performed in >30% of positive cases. All variants identified in
      CDKL5, STXBP1, SCN8A, GABRA1, and FOXG1 were de novo, whereas 85.7% of variants
      in PRRT2 were inherited. SIGNIFICANCE: Using a combined approach of NGS and exon
      level aCGH, testing identified a genetic etiology in 15.4% of patients in this
      cohort and revealed the age at molecular diagnosis for patients. Our study
      highlights both high- and low-yield genes associated with epilepsy and
      neurodevelopmental disorders, indicating which genes may be considered for
      molecular diagnostic testing.

PMID- 29655204
TI  - Frustrated Helicity: Joining the Diverging Ends of a Stable Aromatic Amide Helix
      to Form a Fluxional Macrocycle.
AB  - Macrocyclization of a stable two-turn helical aromatic pentamide, that is, an
      object with diverging ends that are not prone to cyclization, was made possible
      by the transient introduction of disruptors of helicity in the form of acid
      labile dimethoxybenzyl tertiary amide substituents. After removal of the helicity
      disruptors, NMR, X-ray crystallography, and computational studies show that the
      macrocycle possesses a strained structure that tries to gain as high a helical
      content as possible despite being cyclic. Two points of disruption of helicity
      remain, in particular a cis amide bond. This point of disruption of helicity can
      propagate along the cycle in a fluxional manner according to defined trajectories
      to produce ten degenerate conformations.

PMID- 29655205
TI  - Paediatric palliative care should focus on living as well as dying.

PMID- 29655206
TI  - Emotion regulation and well-being in primary classrooms situated in low
      socioeconomic communities.
AB  - BACKGROUND: Although emotion is central to most models of children's well-being,
      few studies have looked at how well-being is related to the ways in which
      children regulate their emotions. AIMS: The aim of this study was to examine the
      associations among children's emotion regulation strategy choice and their
      emotional expression, behaviour, and well-being. The study also investigated
      whether contextual factors influenced the emotion regulation strategies children
      chose to use. SAMPLE: Participants (N = 33) were selected from four Year 5/6
      composite classrooms situated in low-socioeconomic urban communities in New
      Zealand. METHOD: Questionnaires were used to measure children's well-being and
      teacher-reported emotional and behavioural problems. Emotional expression and
      emotion regulation strategies were measured through video-recorded observations
      in the classroom. A total of 1,184 instances of emotion regulation strategy use
      were coded using a framework based on Gross' process model of emotion regulation.
      RESULTS: The findings highlight the complexity of the relations among emotion
      regulation, emotion expression, and well-being. Some strategies, such as
      Cognitive Reappraisal, were effective at upregulating negative emotion in the
      short term, yet not strongly associated with well-being. Others, such as
      Situation Modification: Physical, were positively associated with well-being, yet
      not with an immediate change in a child's emotional experience. The findings also
      suggest children flexibly use different strategies in relation to different
      contextual demands. CONCLUSION: These findings may be used to guide future
      intervention efforts which target emotion regulation strategy use as well as
      those which focus on teachers' support of children during emotionally challenging
      situations.

PMID- 29655207
TI  - Tobacco and other occupational exposures among hookah bar workers.

PMID- 29655208
TI  - A Computational Mechanistic Investigation into Reduction of Gold(III) Complexes
      by Amino Acid Glycine: A New Variant for Amine Oxidation.
AB  - Density functional theory (DFT) was utilized to explore the reduction of
      gold(III) complexes by the amino acid glycine (Gly). Interestingly, when the
      nitrogen atom of Gly coordinates to the gold(III) center, its Calpha -hydrogen
      atom becomes so acidic that it can be easily deprotonated by a mild base like
      water. The deprotonation converts the amino acid into a potent reductant by which
      gold(III) is reduced to gold(I) with a moderate activation energy. To our
      knowledge, this is the first contribution suggesting that primary amines are
      oxidized to imines via direct alpha-carbon deprotonation. This finding may
      provide new insights into the mechanistic interpretation of amine oxidations
      catalyzed/mediated by a center with high cathodic reduction potential. This work
      also provides a rationalization behind why gold(III) complexes with amine-based
      polydentate ligands are reluctant to undergo a redox process. Gold(III) reduction
      occurs most efficiently if the Calpha proton leaves in the plane of the Calpha ,
      N and Au atoms. Chelation prevents this alignment, resulting in the gold(III)
      complex being unreactive toward reduction. It has been experimentally found that
      gold(III) is capable of oxidizing Gly to glyoxylic acid (GA) as the initial
      product. The latter, in the presence of another gold(III) complex, has been
      reported to undergo oxidative decarboxylation to afford CO2 and HCOOH. This
      process is found to be mediated by formation of a geminal diol intermediate
      produced by reaction of water with the aldehyde functional group of the
      coordinated GA.

PMID- 29655209
TI  - Hypervalent Iodine Reagents by Anodic Oxidation: A Powerful Green Synthesis.
AB  - The anodic oxidation of aryl iodides is a powerful method for the synthesis of
      hypervalent iodine reagents, which eliminates the necessity to use expensive or
      hazardous chemical oxidizing reagents. The hypervalent iodine reagents generated
      at the anode are successfully used as either in-cell or ex-cell mediators for
      different valuable chemical transformations such as fluorinations and oxidative
      cyclizations. More recently, recyclable mediators and catalytic protocols have
      been developed.

PMID- 29655210
TI  - Interfacial Engineering of Hierarchical Transition Metal Oxide Heterostructures
      for Highly Sensitive Sensing of Hydrogen Peroxide.
AB  - Hydrogen peroxide (H2 O2 ) is a major messenger molecule in cellular signal
      transduction. Direct detection of H2 O2 in complex environments provides the
      capability to illuminate its various biological functions. With this in mind, a
      novel electrochemical approach is here proposed by integrating a series of CoO
      nanostructures on CuO backbone at electrode interfaces. High-resolution
      transmission electron microscopy (HRTEM), X-ray diffraction, and X-ray
      photoelectron spectroscopy demonstrate successful formation of core-shell CuO-CoO
      hetero-nanostructures. Theoretical calculations further confirm energy-favorable
      adsorption of H2 O2 on surface sites of CuO-CoO heterostructures. Contributing to
      the efficient electron transfer path and enhanced capture of H2 O2 in the unique
      leaf-like CuO-CoO hierarchical 3D interface, an optimal biosensor-based CuO-CoO
      2.5 h electrode exhibits an ultrahigh sensitivity (6349 uA m m-1 cm-2 ),
      excellent selectivity, and a wide detection range for H2 O2 , and is capable of
      monitoring endogenous H2 O2 derived from human lung carcinoma cells A549. The
      synergistic effects for enhanced H2 O2 adsorption in integrated CuO-CoO
      nanostructures and performance of the sensor suggest a potential for exploring
      pathological and physiological roles of reactive oxygen species like H2 O2 in
      biological systems.

PMID- 29655211
TI  - The antimicrobial activity of lavender essential oil (Lavandula angustifolia) and
      its influence on the production performance of broiler chickens.
AB  - The aim of the study was the evaluation of the antimicrobial activity (in vitro)
      of lavender (Lavandula angustifolia) essential oil (LEO) and the effect of its
      addition to the drinking water of broiler chickens on their production
      performance. Antimicrobial activity was determined by establishing the minimum
      inhibitory concentration (MIC) using a series of microdilutions. Bird experiments
      were carried out on a commercial farm on 300 Ross 308 broilers. One-day-old
      chicks were randomly assigned to three experimental groups of 100 individuals
      (five replications of 20 individuals each). In the control group, chickens
      received drinking water without added essential oil throughout the rearing
      period. In the LEO0.2 and LEO0.4 groups, from 1 to 42 days of bird life, the
      LEO0.2 group had 0.2 ml/L of essential lavender oil added to the drinking water,
      while LEO0.4 had 0.4 ml/L added. The results of the experiment showed the
      antimicrobial activity of LEO and its positive effect on the production results
      of broiler chickens. Application of higher concentration of essential oil (0.4
      ml/L) significantly affected production results (BW, FCR, WCR-p < .01). No
      differences were observed in FI, WI, F:W and mortality (p > .05). In vitro
      studies indicate a significant effect of LEO on the inhibition of microbial
      growth. These results encourage further studies on a larger scale that will
      confirm antimicrobial efficiency and define the mechanisms of action of Lavandula
      angustifolia essential oil and its individual components.

PMID- 29655212
TI  - Tree differences in primary and secondary growth drive convergent scaling in leaf
      area to sapwood area across Europe.
AB  - Trees scale leaf (AL ) and xylem (AX ) areas to couple leaf transpiration and
      carbon gain with xylem water transport. Some species are known to acclimate in AL
      : AX balance in response to climate conditions, but whether trees of different
      species acclimate in AL  : AX in similar ways over their entire (continental)
      distributions is unknown. We analyzed the species and climate effects on the
      scaling of AL vs AX in branches of conifers (Pinus sylvestris, Picea abies) and
      broadleaved (Betula pendula, Populus tremula) sampled across a continental wide
      transect in Europe. Along the branch axis, AL and AX change in equal proportion
      (isometric scaling: b ~ 1) as for trees. Branches of similar length converged in
      the scaling of AL vs AX with an exponent of b = 0.58 across European climates
      irrespective of species. Branches of slow-growing trees from Northern and
      Southern regions preferentially allocated into new leaf rather than xylem area,
      with older xylem rings contributing to maintaining total xylem conductivity. In
      conclusion, trees in contrasting climates adjust their functional balance between
      water transport and leaf transpiration by maintaining biomass allocation to
      leaves, and adjusting their growth rate and xylem production to maintain xylem
      conductance.

PMID- 29655213
TI  - Evaluation of the Relationship Between the 18S rRNA/rDNA Ratio and Population
      Growth in the Marine Diatom Skeletonema tropicum via the Application of an
      Exogenous Nucleic Acid Standard.
AB  - Ribosomal RNA (rRNA) has been regarded as a proxy for metabolic activity and
      population growth in microbes, but the limitations and assumptions of this
      approach should be better defined, particularly in eukaryotic microalgae. In this
      study, the 18S rRNA/rDNA ratio of a marine diatom, Skeletonema tropicum, was
      examined in batch and semi-continuous cultures subjected to low nitrogen and
      phosphorus treatments at a temperature of 20  degrees C. In the semi-continuous
      cultures, the measured 18S rRNA/rDNA ratio ranged from 4.0 * 102 to 5.0 * 103 ,
      and the logarithmic form of this ratio increased linearly with the population
      growth rate under both low nitrogen and low phosphorus conditions. In batch
      cultures grown under low nitrogen or low phosphorus conditions, log (rRNA/rDNA)
      also increased linearly with growth rate when the latter ranged between -0.4 and
      1.5 day-1 . The 18S rRNA/rDNA ratios of Skeletonema sampled from in the southern
      East China Sea were substantially lower than measured from laboratory cultures.
      Among the field samples, ratios obtained at a coastal station were higher than
      those obtained farther offshore. These results imply higher growth rate at the
      coastal station, but the influences of other factors, such as cell size and
      temperature, cannot be ruled out.

PMID- 29655214
TI  - Molecular and serological surveillance of Hepatitis E virus in wild and domestic
      carnivores in Brandenburg, Germany.
AB  - Hepatitis E virus (HEV) is a zoonotic virus which circulates in pigs and wild
      boars as main reservoir species. To reveal the infection rate in carnivores, we
      have carried out a monitoring study of raccoons, raccoon dogs, dogs and cats
      sampled in Brandenburg, Germany. In summary, 53.8% (43 of 80) of the raccoons,
      34.3% (25 of 73) of the raccoon dogs, 56.6% (47 of 83) of dogs and 32.3% (21 of
      65) of cats were tested positive for HEV-specific antibodies. No viral RNA could
      be detected. This first description of anti-HEV antibodies in raccoons and
      raccoon dogs worldwide and in dogs and cats in Germany highlights the natural
      host range expansion of HEV.

PMID- 29655215
TI  - Alteration of serum thymus and activation-regulated chemokine level during
      biologic therapy for psoriasis: Possibility as a marker reflecting favorable
      response to anti-interleukin-17A agents.
AB  - Biologics show great efficacy in treating psoriasis, a chronic inflammatory skin
      disease. The high cost and side-effects of biologics, dose-reduction, elongation
      of administration interval and suspension are possible options. However, there
      has been no reliable biomarker we can use when we consider these moderations in
      therapy. This study was conducted to test the possibility of using serum thymus
      and activation-regulated chemokine (TARC) level as an indicator for step down of
      biologic therapy. Serum TARC level was measured in 70 psoriatic patients at
      Asahikawa Medical University, and a correlation of TARC and severity of skin
      lesions was analyzed. Referring to serum TARC level, psoriatic patients can be
      divided into two groups. One is a population in which serum TARC level is
      positively correlated with severity of skin lesions, and the other is a
      population with low psoriatic severity and high TARC level. Serum TARC level was
      higher in the group that achieved PASI-clear with biologics than in the group
      which did not achieve PASI-clear. Among biologics, the group treated with
      secukinumab, an anti-interleukin (IL)-17A agent, showed significantly higher TARC
      level compared with the group treated with anti-tumor necrosis factor agents. In
      certain populations achieving PASI-clear, serum TARC level may be a potent marker
      reflecting better response to IL-17A inhibitors, and in this case step down of
      treatment for psoriasis is possible.

PMID- 29655216
TI  - Schizotypal traits are associated with sleep spindles and rapid eye movement in
      adolescence.
AB  - Research suggests an association between schizophrenia and a decrease in sleep
      spindle activity, as well as a change in sleep architecture. It is unknown how
      the continuum of psychotic symptoms relates to different features in the sleep
      electroencephalogram. We set out to examine how sleep architecture and stage 2
      spindle activity are associated with schizotypy in a healthy adolescent
      population. The participants in our study (n = 176, 61% girls) came from a
      community-based cohort. Schizotypal traits were evaluated using the Schizotypal
      Personality Scale (STA) in early adolescence (mean age 12.3 years, SD = 0.5) and
      the participants underwent ambulatory overnight polysomnography at mean age 16.9
      years (SD = 0.1). Sleep was scored in 30-s epochs into stages 1, 2, 3 and rapid
      eye movement (REM) sleep. Stage 2 spindles were detected using an automated
      algorithm. Spindle analyses from central and frontal derivations included spindle
      duration and density for slow (10-13 Hz) and fast (13-16 Hz) ranges. Covariates
      included sex and age. Those with the highest STA scores had a higher percentage
      of REM (B = 2.07 [95% CI, 0.17, 4.0]; p = .03) than those with the lowest scores.
      Those with the highest scores had shorter spindle duration, as derived from the
      frontal regions, and a slower oscillation range (B = -0.04 [95% CI, -0.07, 
      0.01]; p = .023) than those with the lowest scores. We conclude that high levels
      of schizotypy characteristics measured in early adolescence may be associated
      with distinguished features of sleep architecture, namely with spindle morphology
      and a higher proportion of REM sleep.

PMID- 29655217
TI  - The binding interaction between cadmium-based, aqueous-phase quantum dots with
      Candida rugosa lipase.
AB  - As a promising biolabeling biomaterials, quantum dots (QDs) present a great
      potential. However, the toxicity of QDs to organisms has attracted wide
      attention. In our research, we introduced an in vitro method to study the
      molecular mechanisms for the structure and activity alterations of Candida rugosa
      lipase (CRL) with the binding of 3-mercaptopropionic acid-capped CdTe QDs.
      Multiple spectroscopic methods, isothermal titration calorimetry, and enzyme
      activity measurements were used in this paper. QDs statically quenched the
      intrinsic fluorescence of CRL with the quenching constant decreases from 2.46 *
      1013 to 1.64 * 1013  L mol-1  second-1 (298 to 310 K). It binds to CRL through
      hydrophobic force with 1 binding site, unfolding and loosening the skeleton and
      changed its secondary structure. Rather than aggregating on the surface, it
      enters the pocket of the CRL to interact with Ser-209 (2.43 A) and the residues
      surrounding Ser-209, making the catalytic triad more exposed. Furthermore, the
      activity of CRL was inhibited by approximately 15%. This work demonstrates that 3
      mercaptopropionic acid-capped CdTe QDs may cause negative effects to CRL and
      obtains a molecular mechanism on QD-induced toxicity to proteins in vitro.

PMID- 29655218
TI  - Stathmin inhibits proliferation and differentiation of dental pulp stem cells via
      sonic hedgehog/Gli.
AB  - The mineralization of dental pulp stem cells is an important factor in the tissue
      engineering of teeth, but the mechanism is not yet obvious. This study aimed to
      identify the effect of Stathmin on the proliferation and osteogenic/odontoblastic
      differentiation of human dental pulp stem cells (hDPSCs) and to explore whether
      the Shh signalling pathway was involved in this regulation. First, Stathmin was
      expressed in the cytoplasm and on the cell membranes of hDPSCs by cell
      immunofluorescence. Then, by constructing a lentiviral vector, the expression of
      Stathmin in hDPSCs was inhibited. Treatment with Stathmin shRNA (shRNA-Stathmin
      group) inhibited the ability of hDPSCs to proliferate, as demonstrated by a CCK8
      assay and flow cytometry analysis, and suppressed the osteogenic/odontoblastic
      differentiation ability, as demonstrated by alizarin red S staining and
      osteogenic/odontoblastic differentiation-related gene (ALP, BSP, OCN, DSPP)
      activity, compared to that of hDPSCs from the control shRNA group. Molecular
      analyses showed that the Shh/GLI1 signalling pathway was inhibited when Stathmin
      was silenced, and purmorphamine, the Shh signalling pathway activator, was added
      to hDPSCs in the shRNA-Stathmin group, real-time PCR and Western blotting
      confirmed that expression of Shh and its downstream signalling molecules PTCH1,
      SMO and GLI1 increased significantly. After activating the Shh signalling
      pathway, the proliferation of hDPSCs increased markedly, as demonstrated by a
      CCK8 assay and flow cytometry analysis; osteogenic/odontoblastic differentiation
      related gene (ALP, BSP, OCN, DSPP) expression also increased significantly.
      Collectively, these findings firstly revealed that Stathmin-Shh/GLI1 signalling
      pathway plays a positive role in hDPSC proliferation and osteogenic/odontoblastic
      differentiation.

PMID- 29655219
TI  - Hemodynamic Changes May Indicate Vessel Wall Injury After Stent Retrieval
      Thrombectomy for Acute Stroke.
AB  - BACKGROUND AND PURPOSE: Stent retrievers have revolutionized endovascular
      treatment of acute ischemic stroke (AIS). Animal studies showed that mechanical
      thrombectomy (MT) may cause endothelial injury and intimal layer edema. Using
      transcranial color-coded duplex-sonography (TCCS) we observed postprocedural
      hemodynamic changes in the treated vessel. METHODS: We studied AIS patients with
      large intracranial artery occlusion in whom MT with stent retrievers was
      performed. Only those with complete recanalization (modified TICI-2b or 3) as
      assessed by postprocedural digital subtraction angiography (DSA) and in whom
      early control TCCS was performed were retained. Patients treated with intra
      arterial thrombolysis or stenting were excluded. RESULTS: In 31 patients treated
      within a time period of 4 years (29 with middle cerebral artery [MCA] and 2 with
      basilar artery [BA] occlusion), postacute stroke brain-DSA confirmed complete
      recanalization without residual stenosis or vasospasm. However, in 27 (17 men,
      mean age 66.3 years) of them TCCS (mean 3.4 days after MT) showed very segmental
      acceleration of blood flow velocities in the affected arteries (MCA maximum peak
      systolic velocity [PSVmax] at least >35% as compared to the contralateral side at
      the same depth; BA PSVmax >40% as compared to velocities at different depths of
      the same vessel). None showed clinical deterioration. TCCS follow-up (mean 20
      days) showed normalization in 14 of 16 cases. CONCLUSION: Our TCCS study provides
      preliminary evidence of focal acceleration of blood flow velocities after MT.
      Without residual stenosis or vasospasm, this may be a sign of endothelial layer
      disruption/intimal injury. Further studies are needed to confirm our results.

PMID- 29655220
TI  - Graphene-like Molecules with Four Zigzag Edges.
AB  - An efficient synthetic method toward graphene-like molecules (GLMs), having four
      zigzag edges, is described. They were obtained as stable materials and their
      structures were confirmed by X-ray crystallographic analysis. They exhibit
      topology- and size-dependent electronic properties and global aromaticity, which
      are all different from GLMs having either all-armchair edges, or three zigzag
      edges, or two armchair/two zigzag edges. They can be reversibly oxidized and
      reduced into stable charged species, which show fragmental aromatic character to
      minimize anti-aromaticity. Our studies give some new insights into the electronic
      structures and properties of a new type of rarely studied GLMs.

PMID- 29655221
TI  - Rice HRZ ubiquitin ligases are crucial for response to excess iron.
AB  - Iron is essential for virtually all organisms but is toxic when present in
      excess. To acquire the proper amount of iron, plants induce expression of various
      genes involved in iron uptake and translocation in response to low iron
      availability. Two iron-binding ubiquitin ligases, OsHRZ1 and OsHRZ2, negatively
      regulate such iron deficiency responses in rice (Oryza sativa). Transgenic rice
      plants with repressed expression of OsHRZ1 and OsHRZ2 (HRZ knockdown lines) are
      tolerant to low iron availability and accumulate iron in shoots and seeds under
      both iron-sufficient and -deficient conditions without a growth penalty. Although
      the expression of OsHRZ1 and OsHRZ2 is transcriptionally upregulated under iron
      deficient conditions, the physiological relevance of this induction is not known.
      In the present study, we analyzed the response of HRZ knockdown lines to excess
      iron. In the presence of severe excess iron, the HRZ knockdown lines grew worse
      than non-transformants. The HRZ knockdown lines showed stunted shoot and root
      growth and more severe leaf bronzing compared to non-transformants. Moreover,
      these lines accumulated more iron in shoots and exhibited severely elevated
      expression of various genes involved in iron uptake and translocation as well as
      jasmonate signaling compared to non-transformants. These results indicate that
      HRZ ubiquitin ligases are crucial for repressing iron deficiency responses and
      protecting cells from iron toxicity in the presence of excess iron. These results
      support the possibility that HRZs are intracellular Fe sensors and provide clues
      for developing plants tolerant of either iron deficiency or excess with higher
      iron contents in edible parts.

PMID- 29655222
TI  - Fluocinolone acetonide intravitreal implant (Retisert(r) ) in the treatment of
      sight threatening macular oedema of juvenile idiopathic arthritis-related
      uveitis.
AB  - PURPOSE: We describe eight patients with juvenile idiopathic arthritis-related
      chronic uveitis, who received a fluocinolone acetonide implant (FAI, Retisert(r),
      Bausch&Lomb) in one eye. All patients had poor visual acuity (VA) due to
      persistent macular oedema in one or both eyes despite treatment with
      antirheumatic medication. METHODS: Median age of the patients was 22.9 years
      (range, 14.1-39.7) and duration of uveitis 13.0 years (range, 6.8-28.4) at FAI
      implantation. Median preoperative best-corrected visual acuity (BCVA) was 0.1
      (range, 0.05-0.4) and Standardization of Uveitis Nomenclature, SUN-grade was SUN
      2+ (range, 0.5-4.0). All patients had been treated extensively with systemic
      corticosteroids and antirheumatic drugs by the time of FAI implantation. The
      median follow-up time was 5.3 years (range, 4.4-6.3). RESULTS: Macular edema
      resolved in a median time of 0.2 years (range, 0.04-0.39) after the FAI
      implantation. The median BCVA was 0.5-0.63 (range, 0.1-1.0) from 1 to 5 years of
      follow-up. Macular edema did not recur in 5 eyes after the implantation. In three
      eyes, the macular oedema relapsed at 2.7, 2.9 and 5.5 years of follow-up. All our
      patients needed antirheumatic drugs in addition to the FAI to treat their macular
      edema. During the follow-up, 7 eyes required further intraocular operations: 4
      cataract operations, 4 intraocular pressure -lowering operations and 1 retinal
      detachment surgery were performed. CONCLUSION: Fluocinolone acetonide implant is
      a valuable option in the treatment of persistent macular edema associated with
      JIA-related uveitis refractory to systemic treatments.

PMID- 29655223
TI  - Differentiating arterial ischaemic stroke from migraine in the paediatric
      emergency department.
AB  - AIM: To estimate the strengths of association between clinical features and
      migraine or arterial ischaemic stroke (AIS) in children presenting to the
      emergency department. METHOD: Eighty-four children with migraine, prospectively
      recruited from 2009 to 2010, were compared with 55 children with AIS,
      prospectively/retrospectively recruited from 2003 to 2010. Odds ratios were
      calculated via logistic regression to measure associations between clinical
      features and process-of-care factors, and migraine and AIS. RESULTS: Median age
      was 13 years 5 months (interquartile range 12y 11mo-13y 10mo) for migraine and 5
      years (interquartile range 3y 7mo-8y) for patients with AIS. All cases of AIS and
      30% of migraine cases underwent neuroimaging. Over 40% of children with migraine
      had vomiting, numbness, or visual disturbance; other symptoms were uncommon.
      Fifty-five per cent had no signs on physician assessment. Weakness or speech
      disturbance were common in patients with AIS. Significant clinical features
      associated with increased odds of AIS included sudden symptom onset, weakness,
      seizures, speech disturbance, and ataxia, and signs of face, arm, or leg
      weakness, inability to walk, dysarthria, dysphasia, and altered consciousness
      (p<0.05). Significant features associated with decreased odds of AIS included
      older age, vomiting, visual, sensory, other symptoms, and absent focal signs on
      assessment (p<0.05). INTERPRETATION: Presenting features can discriminate
      childhood AIS from migraine. These differences inform decisions about urgency and
      type of neuroimaging in children presenting to the emergency department with
      brain attack symptoms. WHAT THE PAPER ADDS: Weakness, seizures, ataxia, speech,
      or walking difficulties are more frequent in arterial ischaemic stroke (AIS).
      Vomiting, visual, or sensory disturbance and absent focal signs are more frequent
      in migraine. Identifying features of AIS and migraine guides neuroimaging in
      children with brain attack symptoms.

PMID- 29655224
TI  - Improved survival after paediatric stroke - but at what price?

PMID- 29655225
TI  - Acute encephalopathy after febrile status epilepticus: an underdiagnosed,
      misunderstood complication of Dravet syndrome.

PMID- 29655226
TI  - Lead-Free Perovskite Nanowire-Employed Piezopolymer for Highly Efficient Flexible
      Nanocomposite Energy Harvester.
AB  - In the past two decades, mechanical energy harvesting technologies have been
      developed in various ways to support or power small-scale electronics.
      Nevertheless, the strategy for enhancing current and charge performance of
      flexible piezoelectric energy harvesters using a simple and cost-effective
      process is still a challenging issue. Herein, a 1D-3D (1-3) fully piezoelectric
      nanocomposite is developed using perovskite BaTiO3 (BT) nanowire (NW)-employed
      poly(vinylidene fluoride-co-trifluoroethylene) (P(VDF-TrFE)) for a high
      performance hybrid nanocomposite generator (hNCG) device. The harvested output of
      the flexible hNCG reaches up to ~14 V and ~4 uA, which is higher than the current
      levels of even previous piezoceramic film-based flexible energy harvesters.
      Finite element analysis method simulations study that the outstanding performance
      of hNCG devices attributes to not only the piezoelectric synergy of well
      controlled BT NWs and within P(VDF-TrFE) matrix, but also the effective stress
      transferability of piezopolymer. As a proof of concept, the flexible hNCG is
      directly attached to a hand to scavenge energy using a human motion in various
      biomechanical frequencies for self-powered wearable patch device applications.
      This research can pave the way for a new approach to high-performance wearable
      and biocompatible self-sufficient electronics.

PMID- 29655227
TI  - Nanowire-Intensified Metal-Enhanced Fluorescence in Hybrid Polymer-Plasmonic
      Electrospun Filaments.
AB  - Hybrid polymer-plasmonic nanostructures might combine high enhancement of
      localized fields from metal nanoparticles with light confinement and long-range
      transport in subwavelength dielectric structures. Here, the complex behavior of
      fluorophores coupling to Au nanoparticles within polymer nanowires, which
      features localized metal-enhanced fluorescence (MEF) with unique characteristics
      compared to conventional structures, is reported. The intensification effect when
      the particle is placed in the organic filaments is remarkably higher with respect
      to thin films of comparable thickness, thus highlighting a specific, nanowire
      related enhancement of MEF effects. A dependence on the confinement volume in the
      dielectric nanowire is also indicated, with MEF significantly increasing upon
      reduction of the wire diameter. These findings are rationalized by finite element
      simulations, predicting a position-dependent enhancement of the quantum yield of
      fluorophores embedded in the fibers. Calculation of the ensemble-averaged
      fluorescence enhancement unveils the possibility of strongly enhancing the
      overall emission intensity for structures with size twice the diameter of the
      embedded metal particles. These new, hybrid fluorescent systems with localized
      enhanced emission, and the general nanowire-enhanced MEF effects associated to
      them, are highly relevant for developing nanoscale light-emitting devices with
      high efficiency and intercoupled through nanofiber networks, highly sensitive
      optical sensors, and novel laser architectures.

PMID- 29655228
TI  - Efficacy and toxicity of ipilimumab used after nivolumab in patients with
      melanoma.

PMID- 29655230
TI  - ARTHUR J. MOSS MD.

PMID- 29655231
TI  - Noninvasive fetal sex determination by analysis of cell-free fetal DNA in
      maternal capillary blood obtained by fingertip puncture.

PMID- 29655232
TI  - Effects of low-level laser therapy on the healing of surgically closed incisions
      and surgically created open wounds in dogs.
AB  - OBJECTIVE: To determine the effects of low-level laser therapy (LLLT) on
      primarily closed incisions and full thickness open wounds in dogs. STUDY DESIGN:
      Prospective, masked, placebo-controlled design. ANIMAL POPULATION: Healthy intact
      female dogs (n = 10). METHODS: Dogs underwent bilateral flank ovariectomy
      procedures, and open wounds were created bilaterally with a punch biopsy. Each
      side of the dog (incision and open wound) was randomly assigned to the treatment
      (TX) group or the control (CN) group. The TX group received LLLT once daily for 5
      days with a 980-nm laser and a total energy density of 5 J/cm2 . The CN group
      received a sham treatment (laser turned off) for an identical amount of time each
      day. The wounds were assessed visually; measured; photographed at postoperative
      days 3, 7, 11, and 14; and biopsied on postoperative days 7 and 14. A 2-way
      repeated measures multivariate analysis of variance was used to analyze
      differences between groups. RESULTS: There was no difference between groups for
      subjective assessment of healing time and wound measurements (P = .7). There was
      no difference in histopathologic assessment except that the CN group had more
      necrosis and perivascular lymphocytes and macrophages at day 7 (P = .03). The TX
      group had more perivascular lymphocytes and macrophages at day 14 (P = .01).
      CONCLUSION: LLLT did not appear to influence the healing of surgically created
      incisions and small wounds with the methodology reported here. CLINICAL
      SIGNIFICANCE: Results of this study do not support recommending LLLT to stimulate
      healing of uncomplicated, small wounds and incisions.

PMID- 29655233
TI  - A sensitive LC-MS/MS-based bioanalytical method for quantification of
      salviaflaside and rosmarinic acid in rat plasma and its application in a
      pharmacokinetic study.
AB  - A selective and sensitive liquid chromatography tandem mass spectrometry method
      was developed for the simultaneous determination of salviaflaside and rosmarinic
      acid in rat plasma. Sample preparation was carried out through liquid-liquid
      extraction with ethyl acetate using curculigoside as internal standard (IS). The
      analytes were determined by selected reaction monitoring operated in the positive
      ESI mode. Chromatographic separation was performed on an Agilent Eclipse Plus C18
      column (100 * 4.6 mm, 1.8 MUm) with a mobile phase consisting of methanol-water
      formic acid (50:50:0.1, v/v/v) at a flow rate of 0.3 mL/min. The run time was 1.9
      min per sample and the injection volume was 5 MUL. The method had an LLOQ of 1.6
      ng/mL for salviaflaside and 0.94 ng/mL for rosmarinic acid in plasma. The linear
      calibration curves were fitted over the range of 1.6-320 ng/mL for salviaflaside
      and 0.94-188 ng/mL for rosmarinic acid in plasma with correlation coefficients
      (r2 ) >0.99. Intra- and inter-day precisions (relative standard deviation) were <
      13.5%, and accuracies (relative error) were between -8.6% and 14.5% for all
      quality control samples. The method was validated and applied to the
      pharmacokinetics of salviaflaside and rosmarinic acid in plasma after oral
      administration of Prunella vulgaris extract to rats.

PMID- 29655234
TI  - Melatonin protects prepuberal testis from deleterious effects of bisphenol A or
      diethylhexyl phthalate by preserving H3K9 methylation.
AB  - A growing number of couples experience fertility issues with almost half being
      due to malefactors. The exposure to toxic environmental contaminants, such as
      endocrine disruptors (EDs), has been shown to negatively affect male fertility.
      EDs are present in the environment, and exposure to these toxins results in the
      failure of spermatogenesis. The deleterious effects of EDs on spermatogenesis
      have been well documented, whereas improvement of infertility associated with
      spermatogenesis defects remains a great challenge. Herein, we report that in
      vitro exposure of prepuberal mouse testes to two well-known endocrine disruptors
      (EDs), bisphenol A (BPA) or diethylhexyl phthalate (DEHP), impairs
      spermatogenesis with perturbing self-renewal, spermatogonia activity, and
      meiosis. Evidence indicates that such effects are likely due, at least in part,
      to decreased G9a-dependent H3K9 di-methylation. Of note, we found that melatonin
      (MLT) protected the testis from the negative ED impacts with preserving
      spermatogonia stem and meiotic cells, along with maintaining normal H3K9 di
      methylation in these cells. Taken together, this work documents that BPA and EDHP
      adversely affect prepuberal spermatogenesis and perturb crucial epigenetic
      activities in male germ cells and highlight the protective ability of MLT.

PMID- 29655235
TI  - Efficacy of suplatast tosilate in a case of recurrent eosinophilic annular
      erythema.

PMID- 29655236
TI  - The ChOMPS, a new tool to measure oromotor and motor skills for eating and
      drinking.

PMID- 29655237
TI  - Cardiovascular safety signals with dipeptidyl peptidase-4 inhibitors: A
      disproportionality analysis among high-risk patients.
AB  - PURPOSE: In 2008, the US Food and Drug Administration (FDA) issued Draft Guidance
      on investigating cardiovascular risk with oral diabetic drugs, including
      dipeptidyl peptidase-4 inhibitors (DPP-4i). In 2014, underpowered, post hoc
      analyses of clinical trials suggested an increased risk of heart failure with the
      use of these products. As such, we assessed disproportionate reporting of major
      adverse cardiac events (MACE) among reports for DPP-4i submitted to the FDA
      Adverse Event Reporting System (FAERS) from 2006 to 2015. METHODS: We assessed
      the empirical Bayes geometric mean (EBGM) and its lower bound (EB05) of the
      relative reporting ratio for MACE among DPP-4i reports in the full FAERS database
      and in a subset of reports limited to cardiovascular and diabetic drugs. We then
      compared the EB05 in these 2 analyses and calculated the percent positive
      agreement for signals of disproportional reporting (SDRs) involving MACE.
      RESULTS: Of 180.3 million adverse event reports, 13.4 million were for diabetic
      and cardiovascular drugs. In the cardiovascular subset, there was an SDR for
      heart failure with linagliptin (EB05 = 2782.47) and saxagliptin (EB05 = 2.40),
      myocardial infarction with alogliptin (EB05 = 290.11), and cerebral infarction
      with sitagliptin (EB05 = 2.80). Of the 14 MACE, 8 had a percent positive
      agreement >=50% for an SDR in both analyses. Overall, the cardiovascular subset
      elicited 11 more SDRs for DPP-4i than the full dataset. CONCLUSIONS:
      Postmarketing surveillance of DPP-4i through FAERS suggest increased reporting of
      MACE, supporting the current FDA warning of heart failure risk. This suggests the
      need for additional longitudinal, observational research into the association of
      DPP-4i and other MACE.

PMID- 29655238
TI  - Real-Space In Situ Bond Energies: Toward A Consistent Energetic Definition of
      Bond Strength.
AB  - A rigorous definition of intrinsic bond strength based on the partitioning of a
      molecule into real-space fragments is presented. Using the domains provided by
      the quantum theory of atoms-in-molecules (QTAIM) together with the interacting
      quantum atoms (IQA) energetic decomposition, we show how an in situ bond
      strength, matching all the requirements of an intrinsic bond energy, can be
      defined between each pair of fragments. Total atomization or fragmentation
      energies are shown to be equal to the sum of these in situ bond energies (ISBEs)
      if the energies of the fragments are measured with respect to their in-the
      molecule state. These energies usually lie above the ground state of the isolated
      fragments by quantities identified with the standard fragment relaxation or
      deformation energies, which are also provided by the protocol. Deformation
      energies bridge dissociation energies with ISBEs, and can be dissected by using
      well-known tools of real-space theories of chemical bonding. Similarly, ISBEs can
      be partitioned into ionic and covalent contributions, and this feature adds to
      the chemical appeal of the procedure. All the energetic quantities examined are
      observable and amenable, in principle, to experimental determination. Several
      systems, exemplifying the role of each energetic term presented herein, are used
      to show the power of the approach.

PMID- 29655239
TI  - Measuring medical students' attitudes and knowledge about geriatrics and
      gerontology in Brazilian medical students: A comparison of instruments.
AB  - OBJECTIVE: To compare instruments available for evaluating attitudes and
      knowledge about geriatrics and gerontology. METHODS: This cross-sectional study
      investigated 83 third-year Brazilian medical students (with exposure to
      geriatrics and gerontology) and 75 incoming students (with no exposure to this
      content). We used the University of California at Los Angeles Geriatrics
      Attitudes Scale, Palmore's Facts on Aging Quiz, modified Maxwell-Sullivan
      Attitude Survey, Aging Semantic Differential Scale and an instrument assessing
      their cognitive knowledge in geriatrics. RESULTS: The instruments investigated
      had moderate-to-high correlations when evaluating similar constructs, had
      satisfactory or borderline internal consistency for the most part (Cronbach's
      alpha: 0.62-0.94) and were capable of discriminating between students exposed or
      not to practical and theoretical content. CONCLUSION: Our findings reinforce
      previous studies that these scales are capable of differentiating students who
      have or have not had exposure/intervention and, in general, seem to be assessing
      different constructs.

PMID- 29655240
TI  - A Pseudo-Octahedral Cobalt(II) Complex with Bispyrazolylpyridine Ligands Acting
      as a Zero-Field Single-Molecule Magnet with Easy Axis Anisotropy.
AB  - The homoleptic mononuclear compound [Co(bpp-COOMe)2 ](ClO4 )2  (1) (bpp
      COOMe=methyl 2,6-di(pyrazol-1-yl)pyridine-4-carboxylate) crystallizes in the
      monoclinic C2/c space group, and the cobalt(II) ion possesses a pseudo-octahedral
      environment given by the two mer-coordinated tridentate ligands. Direct-current
      magnetic data, single-crystal torque magnetometry, and EPR measurements disclosed
      the easy-axis nature of this cobalt(II) complex, which shows single-molecule
      magnet behavior when a static field is applied in alternating-current
      susceptibility measurements. Diamagnetic dilution in the zinc(II) analogue
      [Zn(bpp-COOMe)2 ](ClO4 )2  (2) afforded the derivative [Zn0.95 Co0.05 (bpp
      COOMe)2 ](ClO4 )2  (3), which exhibits slow relaxation of magnetization even in
      zero field thanks to the reduction of dipolar interactions. Theoretical
      calculations confirmed the overall electronic structure and the magnetic scenario
      of the compound as drawn by experimental data, thus confirming the spin-phonon
      Raman relaxation mechanism, and a direct quantum tunneling in the ground state as
      the most plausible relaxation pathway in zero field.

PMID- 29655241
TI  - Transformation of Perovskite BaBiO3 into Layered BaBiO2.5 Crystals Featuring
      Unusual Chemical Bonding and Luminescence.
AB  - Engineering oxygen coordination environments of cations in oxides has received
      intense interest thanks to the opportunities for the discovery of novel oxides
      with unusual properties. Herein, the synthesis of stoichiometric layered BaBiO2.5
      by a nontopotactic phase transformation of perovskite BaBiO3 is presented. By
      analyzing the synchrotron X-ray diffraction data by the maximum-entropy
      method/Rietveld technique, it was found that Bi is involved in an unusual
      chemical bonding situation with four oxygen atoms featuring one ionic bond and
      three covalent bonds, which results in an asymmetric coordination geometry.
      Photophysical characterization revealed that this peculiar structure shows near
      infrared luminescence differing from that of conventional Bi-containing
      compounds. Experimental and theoretical results led to the proposal of an
      excitonic nature of the luminescence. This work highlights that synthesizing
      materials with uncommon Bi-O bonding and Bi coordination geometry provides a
      pathway to the discovery of systems with new functionalities. This could inspire
      interest in the exploration of a range of materials containing heavier p-block
      elements with prospects for finding systems with unusual properties.

PMID- 29655242
TI  - The tomato MAX1 homolog, SlMAX1, is involved in the biosynthesis of tomato
      strigolactones from carlactone.
AB  - Strigolactones (SLs) are rhizosphere signalling molecules exuded by plants that
      induce seed germination of root parasitic weeds and hyphal branching of
      arbuscular mycorrhiza. They are also phytohormones regulating plant architecture.
      MORE AXILLARY GROWTH 1 (MAX1) and its homologs encode cytochrome P450 (CYP)
      enzymes that catalyse the conversion of the strigolactone precursor carlactone to
      canonical strigolactones in rice (Oryza sativa), and to an SL-like compound in
      Arabidopsis. Here, we characterized the tomato (Solanum lycopersicum) MAX1
      homolog, SlMAX1. The targeting induced local lesions in genomes method was used
      to obtain Slmax1 mutants that exhibit strongly reduced production of orobanchol,
      solanacol and didehydro-orobanchol (DDH) isomers. This results in a severe
      strigolactone mutant phenotype in vegetative and reproductive development.
      Transient expression of SlMAX1 - together with SlD27, SlCCD7 and SlCCD8 - in
      Nicotiana benthamiana showed that SlMAX1 catalyses the formation of carlactonoic
      acid from carlactone. Plant feeding assays showed that carlactone, but not 4
      deoxy-orobanchol, is the precursor of orobanchol, which in turn is the precursor
      of solanacol and two of the three DDH isomers. Inhibitor studies suggest that a 2
      oxoglutarate-dependent dioxygenase is involved in orobanchol biosynthesis from
      carlactone and that the formation of solanacol and DDH isomers from orobanchol is
      catalysed by CYPs.

PMID- 29655244
TI  - Clinical features and repair options for nonmelanoma skin cancers of the eyebrow.

PMID- 29655245
TI  - Management of fever and neutropenia in children with cancer: A survey of
      Australian and New Zealand practice.
AB  - AIM: Variation in the management of fever and neutropenia (FN) in children is
      well described. The aim of this study was to explore the current management of FN
      across Australia and New Zealand and highlight areas for improvement. METHODS: A
      practice survey was administered to paediatric health-care providers via four
      clinical and research networks. Using three clinical case vignettes, we explored
      risk stratification, empiric antibiotics, initial investigations, intravenous
      oral switch, ambulatory management and antibiotic duration in children with
      cancer and FN. RESULTS: A response was received from 104 participants from 16
      different hospitals. FN guideline compliance was rated as moderate or poor by 24%
      of respondents, and seven different fever definitions were described. There was
      little variation in the selected empiric monotherapy and dual-therapy regimens,
      and almost all respondents recommended first-dose antibiotics within 1 h.
      However, 27 different empiric antibiotic combinations were selected for beta
      lactam allergy. An incorrect risk status was assigned to the low-risk case by 27%
      of respondents and to the high-risk case by 41%. Compared to current practice,
      significantly more respondents would manage the low-risk case in the ambulatory
      setting provided adequate resources were in place (43 vs. 85%, P < 0.0001). There
      was variation in the use of empiric glycopeptides as well as use of
      aminoglycosides beyond 48 h. CONCLUSION: Although the antibiotics selected for
      empiric management of FN are appropriate and consistent, variation and
      inaccuracies exist in risk stratification, the selection of monotherapy over dual
      therapy, empiric antibiotics chosen for beta-lactam allergy, use of glycopeptides
      and duration of aminoglycosides.

PMID- 29655246
TI  - Pediatric case of generalized pustular psoriasis developing acute pancreatitis.

PMID- 29655251
TI  - Ultrasound-Assisted Assessment of Medial Elbow Stability.
AB  - OBJECTIVES: An assessment of medial elbow stability is essential to the patient
      with an ulnar collateral ligament injury. Ultrasound imaging can be used to
      assess medial elbow stability. This study determined the effect of the elbow
      flexion angle on the medial elbow joint space during clinical tests of medial
      elbow stability. METHODS: Ultrasound images of the nondominant elbow were
      collected during 3 tests of medial elbow stability: valgus stress test, weighted
      valgus test, and milking maneuver. The elbow flexion angle increased between the
      valgus stress test and milking maneuver. The width of the medial joint space was
      measured on ultrasound images collected in unstressed and stressed conditions.
      RESULTS: Across test conditions, the medial joint width was greater in the
      stressed condition (mean +/- SD, 3.7 +/- 0.1 mm) than in the unstressed condition
      (2.9 +/- 0.09 mm). The medial elbow joint space width was less (mean difference,
      0.16 +/- 0.01 mm; P = .01) in the milking maneuver position compared to the
      valgus stress test positions. CONCLUSIONS: This study provides evidence that
      changes in the width of the medial elbow during clinical evaluation of the
      unimpaired elbow can be detected by ultrasound. Changing the elbow flexion angle
      did not affect the change in width of the medial elbow during valgus loading.

PMID- 29655253
TI  - The role of interleukin-4 in rheumatic diseases.
AB  - Rheumatism is a group of diseases, most of which are autoimmune diseases, that
      violate joints, bones, muscles, blood vessels and related soft tissue. As is well
      known, cytokines play a role in the pathogenesis of several rheumatic diseases,
      such as rheumatoid arthritis, spondyloarthritides, and systemic lupus
      erythematosus. Recently, the role of interleukin-4 (IL-4), which may participate
      in the mechanism of rheumatism, have been discovered. It is reported that IL-4
      takes part in the regulation of T cell activation, differentiation,
      proliferation, and survival of different T cell types. IL-4 also has an
      immunomodulatory effect on B cells, mast cells, macrophages, and many cell types.
      A review of the literature on functions of IL-4 in rheumatic diseases is
      presented.

PMID- 29655254
TI  - A Review and Proposed Rationale for the use of Ultrasonography as a Diagnostic
      Modality in the Identification of Bone Stress Injuries.
AB  - Bone stress injuries are common in military personnel and athletes. The delayed
      diagnosis of a bone stress injury can lead to a more severe injury that requires
      a longer period of treatment. The early detection of bone stress injuries is a
      central part of management. Currently, the reference standard for detecting bone
      stress injuries is magnetic resonance imaging. However, the expanding use of
      point-of-care ultrasonography (US) may enable the early detection of bone stress
      injuries in the clinical setting. In this article, we review the US detection of
      bone stress injuries, as well as discuss the rationale for the use of US in the
      diagnosis of these injuries.

PMID- 29655255
TI  - TP53INP1 inhibits hypoxia-induced vasculogenic mimicry formation via the
      ROS/snail signalling axis in breast cancer.
AB  - Tumour protein p53-inducible nuclear protein 1 (TP53INP1) is a tumour suppressor
      associated with malignant tumour metastasis. Vasculogenic mimicry (VM) is a new
      tumour vascular supply pattern that significantly influences tumour metastasis
      and contributes to a poor prognosis. However, the molecular mechanism of the
      relationship between TP53INP1 and breast cancer VM formation is unknown. Here, we
      explored the underlying mechanism by which TP53INP1 regulates VM formation in
      vitro and in vivo. High TP53INP1 expression was not only negatively correlated
      with a poor prognosis but also had a negative relationship with VE-cadherin, HIF
      1alpha and Snail expression. TP53INP1 overexpression inhibited breast cancer
      invasion, migration, epithelial-mesenchymal transition (EMT) and VM formation;
      conversely, TP53INP1 down-regulation promoted these processes in vitro by
      functional experiments and Western blot analysis. We established a hypoxia model
      induced by CoCl2 and assessed the effects of TP53INP1 on hypoxia-induced EMT and
      VM formation. In addition, we confirmed that a reactive oxygen species (ROS)
      mediated signalling pathway participated in TP53INP1-mediated VM formation.
      Together, our results show that TP53INP1 inhibits hypoxia-induced EMT and VM
      formation via the ROS/GSK-3beta/Snail pathway in breast cancer, which offers new
      insights into breast cancer clinical therapy.

PMID- 29655256
TI  - In vitro gas and methane production in rumen fluid from dairy cows fed grass
      silages differing in plant maturity, compared to in vivo data.
AB  - The relationship between in vitro rumen CH4 production of grass silages, using
      the gas production technique, and in vivo data obtained with the same cows and
      rations in respiration chambers was investigated. Silages were made from grass
      harvested in 2013 on May 6th, May 25th, July 1st and July 8th. The grass silages
      were used to formulate four different rations which were fed to 24 cows in early
      and late lactation, resulting in a slightly different dry matter intake (DMI;
      16.5 kg/day vs. 15.4 kg/day). The experimental rations consisted of 70% grass
      silage, 10% maize silage, and 20% concentrates on a dry matter basis. Cows were
      adapted to the rations for 17 days before rumen fluid was collected via
      oesophageal tubing, and in vitro gas and CH4 production were analysed. In vitro
      total gas and CH4 production of the (ensiled) grass expressed as ml/g OM
      decreased with advancing maturity of the grass. The in vitro CH4 production after
      48 hr of incubation expressed in ml/g OM did not correlate with the in vivo CH4
      production expressed in g/kg organic matter intake or g/kg DMI (R2  = .00-.18, p
      >= .287). The differences in CH4 emission per unit of intake observed in vivo
      were rather small between the different rations, which also contributed to the
      observed poor relationship. Utilizing stepwise multiple regression improved the
      correlation only slightly. In vitro gas and CH4 production varied based on
      whether donor cows were previously adapted to the respective ration or not,
      suggesting that careful adaption to the experimental diet should be envisaged in
      in vitro gas and CH4 production experiments.

PMID- 29655257
TI  - Neuroplasticity and network connectivity of the motor cortex following stroke: A
      transcranial direct current stimulation study.
AB  - Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation
      technique that has potential for clinical utility in neurorehabilitation.
      However, recent evidence indicates that the responses to tDCS are highly
      variable. This study investigated whether electroencephalographic (EEG) measures
      of functional connectivity of the target network were associated with the
      response to ipsilesional anodal tDCS in stroke survivors. Ten chronic stroke
      patients attended two experimental sessions in a randomized cross-over trial and
      received anodal or sham tDCS. Single-pulse transcranial magnetic stimulation was
      used to quantify change in corticospinal excitability following tDCS. At the
      beginning of each session, functional connectivity was estimated using the
      debiased-weighted phase lag index from EEG recordings at rest. Magnetic resonance
      imaging identified lesion location and lesion volume. Partial least squares
      regression identified models of connectivity which maximally accounted for
      variance in anodal tDCS responses. Stronger connectivity of a network with a seed
      approximating the stimulated ipsilesional motor cortex, and clusters of
      electrodes approximating the ipsilesional parietal cortex and contralesional
      frontotemporal cortex in the alpha band (8-13 Hz) was strongly associated with a
      greater increase of corticospinal excitability following anodal tDCS. This
      association was not observed following sham stimulation. Addition of a structural
      measure(s) of injury (lesion volume) provided an improved model fit for
      connectivity between the seed electrode and ipsilesional parietal cortex, but not
      the contralesional frontotemporal cortex. TDCS has potential to greatly assist
      stroke rehabilitation and functional connectivity appears a robust and specific
      biomarker of response which may assist clinical translation of this therapy.

PMID- 29655258
TI  - Bidirectional examination of the interaction between time and numerosity
      corroborates that numerosity influences time estimation but not vice versa.
AB  - There has been great interest in the idea that time, number, and space share a
      common magnitude system. However, only a handful of studies examined
      bidirectional interaction between time and number and the results varied
      depending on the specifics of the methods and stimulus properties of each study.
      The present study investigated bidirectional interaction between time and number
      using estimation tasks. We used duration (Experiment 1) and numerosity
      (Experiment 2) estimation tasks to investigate the effect of numerosity-on
      duration and duration-on-numerosity estimation. The results from the two
      experiments demonstrated that numerosity influences duration processing but not
      vice versa; that is, there was unidirectional interaction between numerosity and
      time. The duration of stimulus presentation was overestimated for stimuli larger
      in (task-irrelevant) numerosity. Possible mechanisms underlying the
      unidirectional interaction between time and number are discussed.

PMID- 29655259
TI  - Emergent niche structuring leads to increased differences from neutrality in
      species abundance distributions.
AB  - Species abundance distributions must reflect the dynamic processes involved in
      community assembly, but whether and when specific processes lead to
      distinguishable signals is not well understood. Biodiversity and species
      abundances may be shaped by a variety of influences, but particular attention has
      been paid to competition, which can involve neutral dynamics, where competitor
      abundances are governed only by demographic stochasticity and immigration, and
      dynamics driven by trait differences that enable stable coexistence through the
      formation of niches. Key recent studies of the species abundance patterns of
      communities with niches employ simple models with pre-imposed niche structure.
      These studies suggest that species abundance distributions are insensitive to the
      relative contributions of niche and neutral processes, especially when diversity
      is much higher than the number of niches. Here we analyze results from a
      stochastic population model with competition driven by trait differences. With
      this model, niche structure emerges as clumps of species that persist along the
      trait axis, and leads to more substantial differences from neutral species
      abundance distributions than have been previously shown. We show that
      heterogeneity in "between-niche" interaction strength (i.e., in the strength of
      competition between species in different niches) plays the dominant role in
      shaping the species abundances along the trait axis, acting as a biotic filter
      favoring species at the centers of niches. Furthermore, we show that
      heterogeneity in "within-niche" interactions (i.e., in the competition between
      species in the same niche) counteracts the influence of heterogeneity in "between
      niche" interactions on the SAD to some degree. Our results suggest that
      competitive interactions that produce niches can also influence the shapes of
      SADs.

PMID- 29655260
TI  - Joint tagging assisted fluctuation nanoscopy enables fast high-density super
      resolution imaging.
AB  - In fluctuation-based optical nanoscopy, investigating high-density labeled
      subcellular structures with high fidelity has been a significant challenge. In
      this study, based on super-resolution radial fluctuation (SRRF) microscopy, the
      joint tagging (JT) strategy is employed to enable fast high-density nanoscopic
      imaging and tracking. In fixed cell experiment, multiple types of quantum dots
      with distinguishable fluorescence spectra are jointly tagged to subcellular
      microtubules. In each spectral channel, the decrease in labeling density
      guarantees the high-fidelity super-resolution reconstruction using SRRF
      microscopy. Subsequently, the combination of all spectral channels achieves high
      density super-resolution imaging of subcellular microtubules with a resolution of
      ~62 nm using JT assisted SRRF technique. In the live-cell experiment, 3-channel
      JT is utilized to track the dynamic motions of high-density toxin-induced lipid
      clusters for 1 minute, achieving the simultaneous tracking of many individual
      toxin-induced lipid clusters spatially distributed significantly below the
      optical diffraction limit in living cells.

PMID- 29655261
TI  - Emerging psychiatric disorders in Kleine-Levin syndrome.
AB  - In Kleine-Levin syndrome (KLS), episodes of hypersomnia and cognitive,
      psychiatric and behavioural disturbances alternate with asymptomatic periods in
      adolescents. We evaluated whether psychiatric disorders would emerge during
      asymptomatic periods in a naturalistic, uncontrolled clinical cohort. Patients
      with primary KLS underwent psychiatric interviews at diagnosis and every year for
      1-10 years, leading to diagnosis of former and present comorbid psychiatric
      disorders. Among the 115 patients (65.2% male and aged 16.1 +/- 4.8 years at KLS
      onset), 19 (16.5%) had a history of psychiatric disorder prior to KLS onset,
      which persisted afterwards in 10. Twenty-five (21%) patients developed a new,
      comorbid psychiatric disorder 1-6 years after KLS onset, during 'asymptomatic'
      periods, including mood disorders (n = 14; including major depressive episodes, n
      = 8; recurrent depressive episodes, n = 2; bipolar I disorder, n = 1; dysthymic
      disorder, n = 1; adjustment disorder with depressive mood, n = 1; and mood
      disorder not otherwise specified, n = 1), anxiety disorders (n = 7), eating
      disorders (n = 2), psychotic disorders not otherwise specified (n = 2),
      schizoaffective disorder (n = 1) and cannabis dependence (n = 1). Six patients
      attempted suicide: two before and two after KLS onset, and two during episodes.
      Female sex, longer disease course, longer time incapacitated (356 +/- 223 versus
      155 +/- 186 days) and more frequent psychiatric symptoms during episodes (but no
      family or personal history of psychiatric disorders) were associated with
      emerging psychiatric disorders. Contrary to the alleged benignity of KLS and
      normality between episodes, one KLS patient in five suffers from emerging
      psychiatric disorders. These disorders may depend on personal vulnerability and,
      most probably, on psychiatric symptoms during episodes.

PMID- 29655262
TI  - Linear immunoglobulin A bullous dermatosis limited to oral mucosa associated with
      ulcerative colitis.

PMID- 29655263
TI  - Distinguishable Detection of Ultraviolet, Visible, and Infrared Spectrum with
      High-Responsivity Perovskite-Based Flexible Photosensors.
AB  - Distinguishable detection of the ultraviolet, visible, and infrared spectrum is
      promising and significant for the super visual system of artificial
      intelligences. However, it is challenging to provide a photosensor with such
      broad spectral response ability. In this work, the ultraviolet, visible, and
      infrared spectrum is distinguished by developing serial photosensors based on
      perovskite/carbon nanotube hybrids. Oraganolead halide perovskites (CH3 NH3 PbX3
      ) possess remarkable optoelectronic properties and tunable optical band gaps by
      changing the halogens, and integration with single-walled carbon nanotubes can
      further improve their photoresponsivities. The CH3 NH3 PbCl3 -based photosensor
      shows a responsivity up to 105 A W-1 to ultraviolet and no obvious response to
      visible light, which is superior to that of most ultraviolet sensors. The CH3 NH3
      PbBr3 -based photosensor exhibits a high responsivity to visible light. Serial
      devices of the two hybrid photosensors with comparable electric and sensory
      performances can distinguish the spectrum of ultraviolet, visible, and infrared
      even with varying light intensities. The photosensors also demonstrate excellent
      mechanical flexibility and bending stability. By taking full advantages of the
      oraganolead halide perovskites, this work provides flexible high-responsivity
      photosensors specialized for ultraviolet, and gives a simple strategy for
      distinguishable detection of ultraviolet, visible, and infrared spectrum based on
      the serial flexible photosensors.

PMID- 29655264
TI  - Trigeminal autonomic cephalgia: A rare cause of headache in children.

PMID- 29655266
TI  - The kinases male germ cell-associated kinase and cell cycle-related kinase
      regulate kinesin-2 motility in Caenorhabditis elegans neuronal cilia.
AB  - Kinesin-2 motors power anterograde intraflagellar transport (IFT), a highly
      ordered process that assembles and maintains cilia. However, it remains elusive
      how kinesin-2 motors are regulated in vivo. Here, we performed forward genetic
      screens to isolate suppressors that rescue the ciliary defects of OSM-3-kinesin
      (homolog of mammalian homodimeric kinesin-2 KIF17) mutants in Caenorhabditis
      elegans. We identified the C. elegans dyf-5 and dyf-18, which encode the homologs
      of mammalian male germ cell-associated kinase and cell cycle-related kinase,
      respectively. Using time-lapse fluorescence microscopy, we show that DYF-5 and
      DYF-18 are IFT cargo molecules and are enriched at the distal segments of sensory
      cilia. Mutations of dyf-5 and dyf-18 generate elongated cilia and ectopic
      localization of the heterotrimeric kinesin-2 (kinesin-II) at the ciliary distal
      segments. Genetic analyses reveal that dyf-5 and dyf-18 are important for
      stabilizing the interaction between IFT particles and OSM-3-kinesin. Our data
      suggest that DYF-5 and DYF-18 act in the same pathway to promote handover between
      kinesin-II and OSM-3 in sensory cilia.

PMID- 29655265
TI  - "Ultimately, mom has the call": Viewing clinical trial decision making among
      patients with ovarian cancer through the lens of relational autonomy.
AB  - OBJECTIVE: This study employs the concept of relational autonomy to understand
      how relational encounters with family members (FMs) and care providers may shape
      decisions around ovarian cancer patients' clinical trial (CT) participation. The
      study also offers unique insights into how FMs view patients' decision making.
      METHODS: In-depth interviews were conducted with 33 patients with ovarian cancer
      who had been offered a CT and 39 FMs. Data were inductively analysed using a
      thematic approach and deductively informed by constructs derived from the theory
      of relational autonomy (RA). RESULTS: Patients' relationships, experiences and
      social status were significant resources that shaped their decisions. Patients
      did not give equal weight to all relationships and created boundaries around whom
      to include in decision making. Doctors' recommendations and perceived enthusiasm
      were described as influential in CT decisions. Both patients with ovarian cancer
      and their FMs maintained that patients have the "final say," indicating an
      individualistic autonomy. However, maintaining the "final say" in the decision
      making process is constitutive of patients' relationships, emphasizing a
      relational approach to autonomy. FMs support patients' autonomy and they do so
      particularly when they believe the patient is capable of making the right
      choices. CONCLUSIONS: Although ethical principles underlying informed consent for
      CT participation emphasize individual autonomy, greater attention to relational
      autonomy is warranted for a more comprehensive understanding of CT decision
      making.

PMID- 29655267
TI  - Antibacterial efficacy and mechanisms of action of low power atmospheric pressure
      cold plasma: membrane permeability, biofilm penetration and antimicrobial
      sensitization.
AB  - AIM: The objective of this study was to determine the efficacy and mechanisms of
      inactivation of two clinically relevant ESKAPE bacteria namely Pseudomonas
      aeruginosa and methicillin-resistant Staphylococcus aureus by atmospheric
      pressure cold plasma. METHODS AND RESULTS: Plasma was generated between two brass
      grids by applying a radiofrequency electric field to a flow of helium.
      Intracellular generation of reactive species, alterations in cell membrane, and
      inactivation of bacteria in planktonic or biofilm growth were studied. Results
      were compared with commonly used antimicrobial drugs. Plasma exposure generated
      reactive oxygen and nitrogen species in bacteria, disrupted membrane integrity
      and reduced bacterial load. The efficacy in bacterial inactivation was comparable
      to antibiotics but exhibited a quicker killing rate. The antibacterial effect of
      plasma synergistically increased in association with antibiotics and did not
      diminish over repeated exposures, suggesting no development in bacterial
      resistance. CONCLUSIONS: Through generation of reactive species, cold plasma
      altered cell membrane and effectively inactivated clinically important bacteria,
      both in suspension and in biofilms. SIGNIFICANCE AND IMPACT OF THE STUDY: As cold
      plasma damages different targets in bacterial cells, it emerges as an effective
      strategy used alone or in combination with antimicrobial drugs to control
      microbial infections and prevent the selection of resistant bacterial strains.

PMID- 29655268
TI  - American College of Physicians diabetes guidelines attempt to turn back the
      clock, conflating good HbA1c with hypoglycemia.

PMID- 29655269
TI  - Tunable Multicolor Phosphorescence of Crystalline Polymeric Complex Salts with
      Metallophilic Backbones.
AB  - A total of 35 [Au(NHC)2 ][MX2 ] (NHC=N-heterocyclic carbene; M=Au or Cu;
      X=halide, cyanide or arylacetylide) complex salts were synthesized by co
      precipitation of [Au(NHC)2 ]+ cations and [MX2 ]- anions. These salts contain
      crystallographically determined polymeric Au???Au or Au???Cu interactions and are
      highly phosphorescent with quantum yields up to unity and emission color tunable
      in the entire visible regions. The nature of the emissive excited states is
      generally assigned to ligand (anion)-to-ligand (cation) charge-transfer
      transitions assisted by d10 ???d10 metallophilicity. The emission properties can
      be further tuned by controlled triple-component co-crystallization or by
      epitaxial growth. Correct recipes for white light-emitting phosphors with quantum
      yields higher than 70 % have been achieved by screening the combinatorial pool.

PMID- 29655270
TI  - Correction to: Reassessing the clinical spectrum associated with Hereditary
      Leiomyomatosis and Renal Cell Carcinoma syndrome in French FH mutation carriers.

PMID- 29655271
TI  - Correction to: PUGS: A novel scale to assess perceptions of uncertainties in
      genome sequencing.

PMID- 29655272
TI  - Erratum.

PMID- 29655273
TI  - A review of techniques for visualising soft tissue microstructure deformation and
      quantifying strain Ex Vivo.
AB  - Many biological tissues have a complex hierarchical structure allowing them to
      function under demanding physiological loading conditions. Structural changes
      caused by ageing or disease can lead to loss of mechanical function. Therefore,
      it is necessary to characterise tissue structure to understand normal tissue
      function and the progression of disease. Ideally intact native tissues should be
      imaged in 3D and under physiological loading conditions. The current published in
      situ imaging methodologies demonstrate a compromise between imaging limitations
      and maintaining the samples native mechanical function. This review gives an
      overview of in situ imaging techniques used to visualise microstructural
      deformation of soft tissue, including three case studies of different tissues
      (tendon, intervertebral disc and artery). Some of the imaging techniques
      restricted analysis to observational mechanics or discrete strain measurement
      from invasive markers. Full-field local surface strain measurement has been
      achieved using digital image correlation. Volumetric strain fields have
      successfully been quantified from in situ X-ray microtomography (micro-CT)
      studies of bone using digital volume correlation but not in soft tissue due to
      low X-ray transmission contrast. With the latest developments in micro-CT showing
      in-line phase contrast capability to resolve native soft tissue microstructure,
      there is potential for future soft tissue mechanics research where 3D local
      strain can be quantified. These methods will provide information on the local 3D
      micromechanical environment experienced by cells in healthy, aged and diseased
      tissues. It is hoped that future applications of in situ imaging techniques will
      impact positively on the design and testing of potential tissue replacements or
      regenerative therapies. LAY DESCRIPTION: The soft tissues in our bodies, such as
      tendons, intervertebral discs and arteries, have evolved to have complicated
      structures which deform and bear load during normal function. Small changes in
      these structures can occur with age and disease which then leads to loss of
      function. Therefore, it is important to image tissue microstructure in 3D and
      under functional conditions. This paper gives an overview of imaging techniques
      used to record the deformation of soft tissue microstructures. Commonly there are
      compromises between obtaining the best imaging result and retaining the samples
      native structure and function. For example, invasive markers and dissecting
      samples damages the tissues natural structure, and staining or clearing (making
      the tissue more transparent) can distort tissue structure. Structural deformation
      has been quantified from 2D imaging techniques (digital image correlation) to
      create surface strain maps which help identify local tissue mechanics. When
      extended to 3D (digital volume correlation), deformation measurement has been
      limited to bone samples using X-ray micro-CT. Recently it has been possible to
      image the 3D structure of soft tissue using X-ray micro-CT meaning that there is
      potential for internal soft tissue mechanics to be mapped in 3D. Future
      application of micro-CT and digital volume correlation will be important for soft
      tissue mechanics studies particularly to understand normal function, progression
      of disease and in the design of tissue replacements.

PMID- 29655274
TI  - Granulocyte colony-stimulating factor-producing melanoma treated with the
      combination of dabrafenib and trametinib.

PMID- 29655275
TI  - CO2 laser-assisted sclerectomy surgery compared with trabeculectomy in primary
      open-angle glaucoma and exfoliative glaucoma. A 1-year follow-up.
AB  - PURPOSE: To report on the efficacy and safety of CO2 laser-assisted sclerectomy
      surgery (CLASS) compared with trabeculectomy in primary open-angle glaucoma and
      exfoliative glaucoma. METHODS: One hundred and thirty-one patients underwent
      CLASS (66 patients) or trabeculectomy (65 patients) and were followed up for 12
      months. 'Complete success' was defined as intraocular pressure (IOP) between 10
      and 18 mmHg and reduced by at least 30% from the baseline without medications,
      while 'qualified success' was compliant with the above criteria with or without
      the medications. RESULTS: Comparing CLASS with trabeculectomy at 1 year, the mean
      IOP reduction rate was 32.6 +/- 10.8% versus 40.6 +/- 15.9% (p < 0.001) and the
      average use of medications was 1.4 +/- 1.4 versus 0.7 +/- 1.1 (p < 0.05). At 12
      months, the complete success rate was 35% for CLASS versus 60% for trabeculectomy
      (p < 0.01), while the qualified success rate was 74% versus 75%, respectively,
      with no significant difference in qualified success rate between the groups at
      any time-point (p > 0.05). Compared with CLASS, patients after trabeculectomy
      developed a higher rate of early complications (9.1% versus 29.2%, p = 0.004),
      higher endothelial cell density (ECD) loss (1.4 +/- 1.4% versus 6.5 +/- 4.8%, p <
      0.001), higher astigmatism (0.0 +/- 0.1 versus 0.1 +/- 0.2, p < 0.001) and
      significant visual acuity deterioration (0.1 +/- 0.1; range 0-2 lines versus 0.4
      +/- 0.6; range 0-3 lines, p = 0.016). CONCLUSION: Although CLASS shows a less
      potent hypotensive effect, it is similar to trabeculectomy in the qualified
      success rate and offers the reduction in medications up to 12 months. With a more
      attractive complications profile, CLASS may be an alternative to trabeculectomy,
      especially at the earlier glaucoma stage and in patients with a low ECD.

PMID- 29655277
TI  - Interprofessional, psycho-social intervention to facilitate resilience and reduce
      supportive care needs for patients with cancer: Results of a noncomparative,
      randomized phase II trial.
AB  - OBJECTIVE: We developed 2 intensity levels of a complex intervention for
      interprofessional supportive care in cancer (IPSC-C) to facilitate resilience and
      reduce unmet supportive care needs. We aimed to test the feasibility,
      acceptability, and preliminary effectiveness of both intensity levels in routine
      practice. METHODS: In a randomized, noncomparative phase II trial, newly
      diagnosed patients received either low (LI-IPSC-C) or high (HI-IPSC-C) intensity
      interventions. Low-intensity-interprofessional supportive care in cancer (LI-IPSC
      C) consisted of 3 electronic assessments of resilience, unmet supportive care
      needs, mood, and coping effort over 16 weeks with an immediate feedback to
      clinicians including tailored intervention recommendations to facilitate
      resilience and supportive care. High-intensity-interprofessional supportive care
      in cancer (HI-IPSC-C) added 5 structured consultations (face-to-face and
      telephone) provided by specialized nurses. Primary outcome was a change >=5 in
      resilience score on the Connor-Davidson Resilience Scale (CD-RISC). Secondary
      outcomes were unmet supportive care needs, mood, and coping effort. We assessed
      feasibility by clinician-provided tailored interventions as recommended and
      acceptability through qualitative interviews with clinicians and patients.
      RESULTS: In the LI-IPSC-C arm, 11 of 41, in the HI-IPSC-C arm 17 of 43, patients
      increased resilience scores by >=5. Relatively more patients decreased unmet
      needs in HI-IPSC-C arm. Mood, in both arms, and coping effort, in HI-IPSC-C arm,
      improved meaningfully. Feasibility was limited for the LI-IPSC-C arm, mainly due
      to lack of time; acceptability was high in both arms. CONCLUSION: Neither LI-IPSC
      C nor HI-IPSC-C interventions reached the desired threshold. HI-IPSC-C showed
      positive effects on secondary outcomes and was feasible. Resilience as measured
      by the CD-RISC may not be the optimal outcome measure for this intervention.

PMID- 29655276
TI  - Is sensitization to pig antigens detrimental to subsequent allotransplantation?
AB  - An important question in xenotransplantation is whether an allotransplant can
      safely be carried out in a patient who has become sensitized to a pig xenograft.
      To answer this question, we have searched the literature. We primarily limited
      our review to the clinically relevant pig-to-non-human primate (NHP) model and
      found five studies that explored this topic. No NHP that had received a pig graft
      developed antibodies to alloantigens, and in vitro studies indicated no increased
      humoral and/or cellular alloreactivity. We carried out a small in vitro study
      ourselves that confirmed this conclusion. There have been three experiments in
      which patients undergoing dialysis were exposed to wild-type pig kidneys and
      three clinical studies related to bridging a patient in hepatic failure to liver
      allotransplantation. Despite the development of anti-pig antibodies, all
      subsequent organ (kidney or liver) allografts were successful (except possibly in
      one case). In addition, pig fetal islets were transplanted into patients with
      kidney allografts; there was no increase in panel-reactive alloantibodies and the
      kidney grafts continued to function satisfactorily. In conclusion, the limited
      data suggest that, after sensitization to pig antigens, there is no evidence of
      antibody-mediated or accelerated cellular rejection of a subsequent allograft.

PMID- 29655278
TI  - Residents from non-English-speaking countries of birth in Australian aged care
      facilities.
AB  - OBJECTIVE: To describe the activity of daily living and behavioural and complex
      care needs of residents born in non-English-speaking countries in Australian aged
      care facilities. METHODS: De-identified cross-sectional data were provided by the
      Australian Institute of Health and Welfare for all residents in government-funded
      facilities on 30 June 2015. Analyses included t-tests, chi-squared tests and
      logistic regressions. RESULTS: A total of 33 168 (19%) residents were born in one
      of 188 non-English-speaking countries. Compared to residents born in English
      speaking countries, they were significantly younger, lived in larger facilities,
      were more likely to be male and live in an urban area. Their care requirements
      were greater for activities of daily living and behavioural and complex care.
      Residents from non-English-speaking countries living in ethno-specific facilities
      had higher levels of these needs. CONCLUSION: The needs of residents born in non
      English-speaking countries should be considered when planning aged care services.

PMID- 29655280
TI  - Alteration of layer thickness in the choroid of diabetic patients.
AB  - IMPORTANCE: Choroidal thickness changes in diabetic retinopathy improve
      understanding the pathophysiology and managements of this disease. BACKGROUND: To
      examine the choroidal layer thickness in diabetes mellitus (DM) patients and
      normal individuals, and to compare the findings based on medical history of
      systemic DM treatments, and stage of diabetic retinopathy (DR). DESIGN: Case
      control study. PARTICIPANTS: Two hundred sixty eight eyes of 134 DM patients and
      age-matched 72 healthy controls of 92 eyes. METHODS: Central choroidal layer
      thickness (total, inner, and outer layers) was measured using enhanced depth
      imaging OCT. DM patients were divided into two groups; the DM treated group (88
      cases), and the untreated group (46 cases). These two groups were further
      classified into four groups; no DR (NDR), mild/moderate non-proliferative DR
      (mNPDR), severe NPDR and PDR. MAIN OUTCOME MEASURES: Comparison of subfoveal
      choroid layer thickness in control and diabetic patient groups. RESULTS:
      Choroidal thickness measurements of diabetic eyes had strong correlation between
      masked raters in choroidal layers, proving high reproducibility. The total and
      outer choroid thicknesses in mNPDR in the DM untreated group were significantly
      thinner than normal controls (each P<0.05). Choroidal outer layer thickness of
      the severe NPDR in the DM untreated group was significantly thicker than normal
      controls (P<0.05). In the DM treatment group, there were no significant
      differences from the control group regarding choroidal layer thicknesses and all
      stages of DR. CONCLUSIONS AND RELEVANCE: The choroidal thickness significantly
      changed in the DM untreated group, and the main anatomical changes might result
      from the outer layer.

PMID- 29655279
TI  - A Flexible Caterpillar-Like Gold Nanoparticle Assemblies with Ultrasmall Nanogaps
      for Enhanced Dual-Modal Imaging and Photothermal Therapy.
AB  - Gold nanoparticle (AuNP) assemblies (GNAs) have attracted attention since
      enhanced coupling plasmonic resonance (CPR) emerged in the nanogap between
      coupling AuNPs. For one dimensional GNAs (1D-GNAs), most CPR from the nanogaps
      could be easily activated by electromagnetic waves and generate drastically
      enhanced CPR because the nanogaps between coupling AuNPs are linearly distributed
      in the 1D-GNAs. The reported studies focus on the synthesis of 1D-GNAs and
      fundamental exploration of CPR. There are still problems which impede further
      applications in nanomedicine, such as big size (>500 nm), poor water solubility,
      and/or poor stability. In this study, a kind of 1D flexible caterpillar-like GNAs
      (CL-GNAs) with ultrasmall nanogaps, good water solubility, and good stability is
      developed. The CL-GNAs have a flexible structure that can randomly move to change
      their morphology, which is rarely reported. Numerous ultrasmall nanogaps (<1 nm)
      are linearly distributed along the structure of CL-GNAs and generate enhanced
      CPR. The toxicity assessments in vitro and vivo respectively demonstrate that CL
      GNAs have a low cytotoxicity and good biocompatibility. The CL-GNAs can be used
      as an efficient photothermal agent for photothermal therapy, a probe for Raman
      imaging and photothermal imaging.

PMID- 29655281
TI  - Strongly Coupled Carbon Nanosheets/Molybdenum Carbide Nanocluster Hollow
      Nanospheres for High-Performance Aprotic Li-O2 Battery.
AB  - A highly efficient oxygen electrode is indispensable for achieving high
      performance aprotic lithium-O2 batteries. Herein, it is demonstrated that
      strongly coupled carbon nanosheets/molybdenum carbide (alpha-MoC1-x ) nanocluster
      hierarchical hybrid hollow spheres (denoted as MoC1-x /HSC) can work well as
      cathode for boosting the performance of lithium-O2 batteries. The important
      feature of MoC1-x /HSC is that the alpha-MoC1-x nanoclusters, uniformly
      incorporated into carbon nanosheets, can not only effectively prevent the
      nanoclusters from agglomeration, but also help enhance the interaction between
      the nanoclusters and the conductive substrate during the charge and discharge
      process. As a consequence, the MoC1-x /HSC shows significantly improved
      electrocatalytic performance in an aprotic Li-O2 battery with greatly reduced
      charge and discharge overpotentials and long cycle stability. The ex situ
      scanning electron microscopy, X-ray diffraction, and X-ray photoelectron
      spectroscopy studies reveal that the mechanism for the high-performance Li-O2
      battery using MoC1-x /HSC as cathode is that the incorporated molybdenum carbide
      nanoclusters can make oxygen reduction on their surfaces easy, and finally form
      amorphous film-like Li-deficient Li2 O2 with the ability to decompose at a low
      potential. To the best of knowledge, the MoC1-x /HSC of this paper is among the
      best cathode materials for lithium-O2 batteries reported to date.

PMID- 29655282
TI  - Highly Porous Mn3 O4 Micro/Nanocuboids with In Situ Coated Carbon as Advanced
      Anode Material for Lithium-Ion Batteries.
AB  - The electrochemical performance of most transition metal oxides based on the
      conversion mechanism is greatly restricted by inferior cycling stability, rate
      capability, high overpotential induced by the serious irreversible reactions, low
      electrical conductivity, and poor ion diffusivity. To mitigate these problems,
      highly porous Mn3 O4 micro/nanocuboids with in situ formed carbon matrix (denoted
      as Mn3 O4 @C micro/nanocuboids) are designed and synthesized via a one-pot
      hydrothermal method, in which glucose plays the roles of a reductive agent and a
      carbon source simultaneously. The carbon content, particle size, and pore
      structure in the composite can be facilely controlled, resulting in continuous
      carbon matrix with abundant pores in the cuboids. The as-fabricated Mn3 O4 @C
      micro/nanocuboids exhibit large reversible specific capacity (879 mAh g-1 at the
      current density of 100 mA g-1 ) as well as outstanding cycling stability (86%
      capacity retention after 500 cycles) and rate capability, making it a potential
      candidate as anode material for lithium-ion batteries. Moreover, this facile and
      effective synthetic strategy can be further explored as a universal approach for
      the synthesis of other hierarchical transition metal oxides and carbon hybrids
      with subtle structure engineering.

PMID- 29655283
TI  - Transcription profiling of peripheral B cells in antibody-positive primary
      Sjogren's syndrome reveals upregulated expression of CX3CR1 and a type I and type
      II interferon signature.
AB  - B cells play a key role in the pathogenesis of primary Sjogren's syndrome (pSS).
      The aim of this study was to analyse the transcriptome of CD19+ B cells from
      patients with pSS and healthy controls to decipher the B cell-specific
      contribution to pSS. RNA from purified CD19+ B cells from 12 anti-SSA antibody
      positive untreated female patients with pSS and 20 healthy blood donors was
      subjected to whole transcriptome sequencing. A false discovery rate corrected
      significance threshold of alpha < 0.05 was applied to define differential gene
      expression. As validation, gene expression in B cells from 17 patients with pSS
      and 16 healthy controls was analysed using a targeted gene panel. RNA-sequencing
      identified 4047 differentially expressed autosomal genes in pSS B cells.
      Upregulated expression of type I and type II interferon (IFN)-induced genes was
      observed, establishing an IFN signature in pSS B cells. Among the top upregulated
      and validated genes were CX3CR1, encoding the fractalkine receptor involved in
      regulation of B-cell malignancies, CCL5/RANTES and CCR1. Increased expression of
      several members of the TNF superfamily was also identified; TNFSF4/Ox40L,
      TNFSF10/TRAIL, TNFSF13B/BAFF, TNFRSF17/BCMA as well as S100A8 and 
      A9/calprotectin, TLR7, STAT1 and STAT2. Among genes with downregulated expression
      in pSS B cells were SOCS1 and SOCS3, CD70 and TNFAIP3/A20. We conclude that B
      cells from patients with anti-SSA antibody-positive pSS display immune activation
      with upregulated expression of chemokines, chemokine receptors and a prominent
      type I and type II IFN signature, while suppressors of cytokine signalling are
      downregulated. This adds insight into the autoimmune process and suggests
      potential targets for future functional studies.

PMID- 29655284
TI  - A pair of nonspecific phospholipases C, NPC2 and NPC6, are involved in
      gametophyte development and glycerolipid metabolism in Arabidopsis.
AB  - Phospholipases play crucial roles in plant membrane lipid homeostasis.
      Nonspecific phospholipase C (NPCs) establish a unique class of phospholipases
      found only in plants and certain bacteria. Here, we show that two previously
      uncharacterized NPC isoforms, NPC2 and NPC6, are required for male and female
      gametophyte development in Arabidopsis. Double mutant plants of npc2-1 npc6-2
      could not be retrieved because npc2-1 npc6-2 ovule and pollen development is
      affected. Genetic complementation, reciprocal crossing and microscope observation
      of npc2-1/- npc6-2/+ and npc2-1/+ npc6-2/- plants suggest that NPC2 and NPC6 are
      redundant and are required for normal gametophyte development. Both NPC2 and NPC6
      proteins are localized to the plastids. Promoter-GUS assays in transgenic
      Arabidopsis revealed that NPC2 and NPC6 are preferentially expressed in floral
      organs rather than in leaves. In vitro enzyme assays showed that NPC2 and NPC6
      hydrolyze phosphatidylcholine and phosphatidylethanolamine, but not
      phosphatidate, being consistent with the reported substrate selectivity of NPCs.
      The amounts of phosphatidylcholine, phosphatidylethanolamine and
      phosphatidylglycerol were increased in buds but not in flowers of npc2-1/- npc6
      2/+ and npc2-1/+ npc6-2/- plants, presumably due to reduced phospholipid
      hydrolysis activity in developing flowers. Our results demonstrate that NPC2 and
      NPC6 play crucial roles in gametogenesis during flower development.

PMID- 29655285
TI  - Potent Inhibitors of Plasmodial Serine Hydroxymethyltransferase (SHMT) Featuring
      a Spirocyclic Scaffold.
AB  - With the discovery that serine hydroxymethyltransferase (SHMT) is a druggable
      target for antimalarials, the aim of this study was to design novel inhibitors of
      this key enzyme in the folate biosynthesis cycle. Herein, 19 novel spirocyclic
      ligands based on either 2-indolinone or dihydroindene scaffolds and featuring a
      pyrazolopyran core are reported. Strong target affinities for Plasmodium
      falciparum (Pf) SHMT (14-76 nm) and cellular potencies in the low nanomolar range
      (165-334 nm) were measured together with interesting selectivity against human
      cytosolic SHMT1 (hSHMT1). Four co-crystal structures with Plasmodium vivax (Pv)
      SHMT solved at 2.2-2.4 A resolution revealed the key role of the vinylogous
      cyanamide for anchoring ligands within the active site. The spirocyclic motif in
      the molecules enforces the pyrazolopyran core to adopt a substantially more
      curved conformation than that of previous non-spirocyclic analogues. Finally,
      solvation of the spirocyclic lactam ring of the receptor-bound ligands is
      discussed.

PMID- 29655287
TI  - Effectiveness of interventions on breastfeeding self-efficacy and perceived
      insufficient milk supply: A systematic review and meta-analysis.
AB  - The aim of this systematic review and meta-analysis was to assess the efficacy on
      an intervention on breastfeeding self-efficacy and perceived insufficient milk
      supply outcomes. The literature search was conducted among 6 databases (CINAHL,
      Medline, PsyncInfo, Scopus, Cochrane, and ProQuest) in between January 2000 to
      June 2016. Two reviewers independently assessed the articles for the following
      inclusion criteria: experimental or quasi-experimental studies; healthy pregnant
      women participants intending to breastfeed or healthy breastfeeding women who
      gave birth to a term singleton and healthy baby; intervention administered could
      have been educational, support, psycho-social, or breastfeeding self-efficacy
      based, offered in prenatal or postnatal or both, in person, over the phone, or
      with the support of e-technologies; breastfeeding self-efficacy or perceived
      insufficient milk supply as outcomes. Seventeen studies were included in this
      review; 12 were randomized controlled trials. Most interventions were self
      efficacy based provided on 1-to-1 format. Meta-analysis of RCTs revealed that
      interventions significantly improved breastfeeding self-efficacy during the first
      4 to 6 weeks (SMD = 0.40, 95% CI 0.11-0.69, p = 0.006). This further impact
      exclusive breastfeeding duration. Only 1 study reported data on perceived
      insufficient milk supply. Women who have made the choice to breastfeed should be
      offered breastfeeding self-efficacy-based interventions during the perinatal
      period. Although significant effect of the interventions in improving maternal
      breastfeeding self-efficacy was revealed by this review, there is still a paucity
      of evidence on the mode, format, and intensity of interventions. Research on the
      modalities of breastfeeding self-efficacy should be pursued.

PMID- 29655288
TI  - Modified Tal Score: Validated score for prediction of bronchiolitis severity.
AB  - OBJECTIVE: To further validate the use of the Modified Tal Score (MTS), a
      clinical tool for assessing bronchiolitis severity, by physicians with varying
      experience and training levels, and to determine the ability of the MTS to
      predict bronchiolitis severity. METHODS: This prospective cohort study included
      infants of <12 months of age who were diagnosed with bronchiolitis and assessed
      via MTS. We calculated the intra-class correlation coefficient (ICC) among four
      groups of raters: group 1, board-certified pediatric pulmonologists; group 2,
      board-certified pediatricians; group 3, senior pediatric residents; and group 4,
      junior pediatric residents. Clinical outcomes were determined as length of oxygen
      support and length of stay (LOS). We assessed MTS's prediction of these outcomes.
      Relative risk (RR) for clinical severity was calculated via a Generalized Linear
      Model. RESULTS: Twenty-four physicians recorded a total of 600 scores for 50
      infants (average age 5 +/- 3 months; 56% male). The ICC values with group 1 as a
      reference were 0.92, 0.87, and 0.83, for groups 2, 3, and 4, respectively (P <
      0.001). RR for oxygen support required was; 1.33 (CI 1.12-1.57), 1.26 (1.1-1.46),
      1.26 (1.06-1.5), and 1.21 (0.93-1.58) for groups 1, 2, 3, and 4, respectively. RR
      for LOS was; 1.15 (CI 0.97-1.37), 1.19 (1.03-1.38), 1.18 (1.0-1.39), and 1.18
      (0.93-1.51) for groups 1, 2, 3, and 4, respectively. CONCLUSION: The MTS is a
      simple and valid scoring system for evaluating infants with acute bronchiolitis,
      among different physician groups. The first score upon admission is a fair
      predictor of oxygen requirement at 48 h, and LOS at 72 h.

PMID- 29655286
TI  - Reduced expression of oestrogen receptor-beta is associated with tumour invasion
      and metastasis in oestrogen receptor-alpha-negative human papillary thyroid
      carcinoma.
AB  - Oestrogens play an important role in the development and progression of papillary
      thyroid carcinoma (PTC) through oestrogen receptor (ER)-alpha and -beta, which
      may exert different or even opposing actions in PTC. The roles of ERbeta in
      ERalpha-negative PTC are still not clear. This study investigated the expression
      dynamics of ERbeta1 (wild-type ERbeta) and its clinical significance in female
      ERalpha-negative PTC patients. ERbeta1 expression was detected in thyroid tissues
      of 136 female patients diagnosed with PTC. The relationships between ERbeta1
      expression and clinicopathological/biological factors were also analysed in
      female ERalpha-negative PTC patients. The total score for ERbeta1 was
      significantly lower in female ERalpha-negative PTC patients with LNM or ETE when
      compared to those without LNM or ETE (Z = -2.923, P = 0.003 and Z = -3.441, P =
      0.001). Accordingly, the total score for ERbeta1 was significantly higher in
      ERalpha-negative PTC patients expressing E-cadherin compared to patients negative
      for E-cadherin expression (Z = -2.636, P = 0.008). The total score was lower in
      ERalpha-negative PTC patients positive for VEGF expression compared to those
      negative for VEGF expression (Z = -1.914, P = 0.056). This preliminary study
      indicates that reduced expression of ERbeta1 in female ERalpha-negative PTC
      patients is associated with greater progression of the disease. This may provide
      insights into the underlying molecular mechanisms of ERbeta1 and could help
      design targeted approaches for treating or even preventing this disease.

PMID- 29655289
TI  - Dacryocystitis mimicking erysipelas due to a giant dacryolith.

PMID- 29655290
TI  - Pharmacokinetic and pharmacodynamic profile of the sodium-glucose co-transporter
      2 inhibitor empagliflozin in young people with Type 2 diabetes: a randomized
      trial.
AB  - AIMS: To assess the pharmacokinetic and pharmacodynamic profile of a single dose
      of empagliflozin in young people with Type 2 diabetes to identify the appropriate
      doses for further paediatric development. METHODS: We conducted a single-dose,
      open-label, randomized, parallel-group study with empagliflozin 5 mg, 10 mg and
      25 mg in young people with Type 2 diabetes aged 10-17 years. RESULTS: Of 39
      participants screened, 27 were randomized and completed the study; their mean (+/
      sd) age was 14.1+/-2.0 years and body weight was 96.7+/-23.5 kg. Compared with
      similar studies in adults with Type 2 diabetes, the maximum observed plasma
      concentrations were slightly lower with the 10-mg and 25-mg doses, and the area
      under the plasma concentration-time curve was slightly lower with the 10-mg but
      slightly higher with the 25-mg dose. The adjusted mean increases in urinary
      glucose excretion were 53 g/24 h (95% CI 32,74), 73 g/24 h (95% CI 52,94) and 87
      g/24 h (95% CI 68,107), and the adjusted mean decreases in fasting plasma glucose
      were 0.9 mmol/l (95% CI -1.6,-0.1), 0.9 mmol/l (95% CI -1.7,-0.2) and 1.1 mmol/l
      (95% CI -1.8,-0.5) for the 5- 10- and 25-mg doses, respectively. There were no
      serious adverse events and one investigator-reported drug-related event
      (dehydration). CONCLUSIONS: After a single oral dose of empagliflozin, adults and
      young people with Type 2 diabetes had similar exposure-response relationships
      after adjusting for significant covariates. These data support testing 10-mg
      and/or 25-mg doses of empagliflozin in an upcoming paediatric phase III Type 2
      diabetes trial. (ClinicalTrials.gov registration no.: NCT02121483).

PMID- 29655291
TI  - Sp1-regulated transcription of RasGRP1 promotes hepatocellular carcinoma (HCC)
      proliferation.
AB  - BACKGROUND AND AIMS: The role of Ras guanine nucleotide-releasing protein 1
      (RasGRP1) in tumourigenesis has been a subject of debate, and its functions and
      clinical significance in hepatocellular carcinoma (HCC) remain unknown. Here, we
      evaluated the expression of RasGRP1 in HCC and determined how it contributes to
      HCC cell proliferation. METHODS: RasGRP1 expression was measured by quantitative
      polymerase chain reaction (qPCR) and Western blotting of 24 paired HCC tissues
      and para-tumour tissues. RasGRP1 expression was confirmed by immunohistochemical
      analysis of a tissue microarray from 1 independent cohort. Overall survival (OS)
      and disease-free survival (DFS) were estimated using the Kaplan-Meier method, and
      risk factors that contributed to OS or DFS were identified using Cox regression
      analysis. The biologic relevance of RasGRP1 was examined by small interfering
      RNAs and an exogenous plasmid construct. Chromatin immunoprecipitation assays
      were performed to examine the binding of Sp1 to the RasGRP1 promoter. RESULTS:
      Increased RasGRP1 expression was associated with tumour size (P = .004), tumour
      node-metastasis stage (P = .032), and Barcelona Clinic Liver Cancer stage (P =
      .002). RasGRP1 overexpression was an independent prognostic factor in HCC
      patients. RasGRP1 downregulation inhibited cell proliferation, whereas RasGRP1
      overexpression promoted cell proliferation. Moreover, specificity protein 1 bound
      to the RasGRP1 promoter and promoted RasGRP1 transcription. In addition, RasGRP1
      overexpression enhanced activation of the c-Raf pathway. CONCLUSIONS: RasGRP1 is
      upregulated in HCC and promotes HCC cell proliferation. Thus, RasGRP1 may be a
      novel therapeutic target for HCC.

PMID- 29655292
TI  - High perinatal mortality rates persist in Kirakira: The sustainable development
      goals for health remain out of reach in the provinces of Solomon Islands.
AB  - AIM: This study aimed to calculate the perinatal mortality rate in Kirakira
      Hospital, a remote provincial hospital in Solomon Islands, over a 3-year period,
      from 2014 to 2016. METHODS: A retrospective audit of the labour ward admission
      books for the years 2014-2016 was conducted. Patient files of all perinatal
      deaths and caesarean sections were accessed and reviewed. Stillbirths and early
      neonatal deaths were classified, and results were compared with the national
      health statistics of Australia (2014). RESULTS: Between 2014 and 2016, there were
      1311 births and 40 perinatal deaths (mortality rate of 31 per 1000). This is
      approximately three times the Australian rate of 9.6 deaths per 1000. Of these
      deaths, 28 were stillbirths, and 12 were neonatal deaths. Detailed information
      was available for 88% (35/40) of the perinatal deaths. Only 15 caesarean sections
      (1.1% of deliveries) were performed, compared to a rate of 32.1% of caesarean
      sections in Australia (2014). CONCLUSIONS: Kirakira continues to have a very high
      perinatal mortality rate that has not changed over the last 6 years. The rate is
      double that reported for Solomon Islands in current World Health Organization
      data. This discrepancy is likely due to an absence of clinical data outside of
      the National Referral Hospital in Honiara. This paper identifies clinical
      indicators that could be targeted to help lower the perinatal mortality rate in
      this remote and impoverished community.

PMID- 29655293
TI  - Classifying paroxysmal movement disorders: more genotypes and phenotypes.

PMID- 29655294
TI  - Enantiopure versus Racemic Mixture in Reversible, Two-Step, Single-Crystal-to
      Single-Crystal Transformations of Copper(II) Complexes.
AB  - The reaction of chiral sodium complexes, 1infinity [Na(S-valmetH)]?H2 O (1-S) and
      1infinity [Na(R-valmetH)]?H2 O (1-R), with copper(II) acetate affords chiral one
      dimensional coordination polymers with the formulas 1infinity [Cu(S-valmet)(H2
      O)]?H2 O (2-S) and 1infinity [Cu(R-valmet)(H2 O)]?H2 O (2-R) (R/S-valmetH2 are
      Schiff base proligands resulting from the condensation reactions between o
      vanillin and R/S-methionine). The copper ions are connected by the carboxylato
      groups belonging to the amino-acid moieties, resulting in infinite chains showing
      syn-anti out-of-plane bridging mode. The circular dichroism spectra of 1-S, 1-R,
      2-S, and 2-R confirm their enantiomeric nature. Compounds 2-S and 2-R undergo a
      two-step single-crystal-to-single-crystal transformation, with the elimination of
      the lattice and coordinated water molecules: 1infinity [Cu(S-valmet)(H2 O)]?H2 O
      (2-S)->1infinity [Cu(S-valmet)]?H2 O (3-S?H2 O)->1infinity [Cu(S-valmet)] (3-S)
      and 1infinity [Cu(R-valmet)(H2 O)]?H2 O (2-R)->1infinity [Cu(R-valmet)]?H2 O (3
      R?H2 O)->1infinity [Cu(R-valmet)] (3-R), respectively. During these
      transformations, every pair of face-to-face chains present in 2-S (or 2-R) has
      been "zipped up" into a chiral double chain through the removal of the aqua
      ligands and their replacement by the carboxylato oxygen atoms from the
      neighboring chain. Consequently, each carboxylato group now bridges three copper
      ions. The conversion of the single chains, 2-S and 2-R, into the double chains, 3
      S and 3-R, is accompanied by a change of the strength of the exchange
      interactions between the copper ions: weak antiferromagnetic couplings are
      observed in compound 2-S (J/kB =-1.23(5) K, H=-2J SigmaSi Si+1 ) and relatively
      strong in compound 3-S (J/kB =-76.0(8) K). When the racemic mixture of the
      ligands, R,S-valmetH2 , is employed, in the same experimental conditions, a
      racemic mixture of mononuclear compounds, [Cu(R,S-valmet)(H2 O)2 ]?H2 O (4-RS),
      is obtained. Compound 4-RS also undergoes a SCSC transformation with the
      elimination of the lattice and one of the coordinated water molecules, resulting
      in a racemic mixture of chiral chains, 1infinity [Cu(R-valmet)(H2 O)]?1infinity
      [Cu(S-valmet)(H2 O)] (5-RS). In this compound, the coupling of the copper(II)
      ions within the chains is weak and ferromagnetic (J/kB =+0.10(2) K). These
      results prove that the chirality of the valmetH2 ligands (optically pure or
      racemic mixture) plays a key role in the self-assembly process of the copper(II)
      complexes.

PMID- 29655295
TI  - Humerus photon starvation streak artefact.
AB  - INTRODUCTION: The reduced (attenuated) number of photons passing through the arm
      can result in a combination of fine and thick streak artefacts, particularly with
      the use of thin CT slices and lower radiation dose parameters. This phenomenon is
      known as photon starvation. We noted an abnormal appearance of the humerus when
      imaged with certain arm position. This appearance was thought to be artefact due
      to photon starvation. METHODS: A human radius bone was imaged in different
      positions and the kV and mA were varied in an attempt to reproduce the artefact,
      which would support the hypothesis that the artefact may be caused by bone
      attenuation. RESULTS: Scanning the bone in a different angle and radiation dose
      parameters reproduced the artefactual appearance of the bone. CONCLUSION:
      Performing a chest CT scan with arms up can occasionally result in an abnormal
      appearance to the humerus due to photon starvation artefact. Familiarity with
      this artefact is essential to avoid misinterpretation.

PMID- 29655296
TI  - Short-term effects of heat and cold on respiratory drug use. A time-series
      epidemiological study in A Coruna, Spain.
AB  - The consumption of medication, especially over-the-counter drugs, can reflect
      environmental exposure with a lesser degree of severity in terms of morbidity.
      The non-linear effects of maximum and minimum apparent temperature on respiratory
      drug sales in A Coruna from 2006 to 2010 were examined using a distributed lag
      nonlinear model. In particular, low apparent temperatures proved to be associated
      with increased sales of respiratory drugs. The strongest consistent risk
      estimates were found for minimum apparent temperatures in respiratory drug sales
      with an increase of 33.4% (95% CI, 12.5%-58.0%) when the temperature changed from
      2.8 degrees C to -1.4  degrees C. These findings may serve to guide the planning
      of public health interventions to predict and manage the health effects of
      exposure to the thermal environment for lower degrees of morbidity. More
      precisely, significant increases in the use of measured over-the-counter
      medication could be used to identify and anticipate influenza outbreaks due to a
      more sensitive degree of the data source.

PMID- 29655297
TI  - Understanding of multigene test results among males undergoing germline testing
      for inherited prostate cancer: Implications for genetic counseling.
AB  - BACKGROUND: Genetic testing (GT) for prostate cancer (PCA) is rising, with
      limited insights regarding genetic counseling (GC) needs of males. Genetic
      Evaluation of Men (GEM) is a prospective multigene testing study for inherited
      PCA. Men undergoing GC were surveyed on knowledge of cancer risk and genetics
      (CRG) and understanding of personal GT results to identify GC needs. METHODS: GEM
      participants with or high-risk for PCA were recruited. Pre-test GC was in-person,
      with video and handout, or via telehealth. Post-test disclosure was in-person, by
      phone, or via telehealth. Clinical and family history data were obtained from
      participant surveys and medical records. Participants completed measures of
      knowledge of CRG, literacy, and numeracy pre-test and post-test. Understanding of
      personal genetic results was assessed post-test. Factors associated with
      knowledge of CRG and understanding of personal genetic results were examined
      using multivariable linear regression or McNemar's test. RESULTS: Among 109 men
      who completed pre- and post-GT surveys, multivariable analysis revealed family
      history meeting hereditary cancer syndrome (HCS) criteria was significantly
      predictive of higher baseline knowledge (P = 0.040). Of 101 men who responded
      definitively regarding understanding of results, 13 incorrectly reported their
      result (McNemar's P < 0.001). Factors significantly associated with discordance
      between reported and actual results included having a variant of uncertain
      significance (VUS) (P < 0.001) and undergoing GC via pre-test video and post-test
      phone disclosure (P = 0.015). CONCLUSIONS: While meeting criteria for HCS was
      associated with higher knowledge of CRG, understanding of personal GT results was
      lacking among a subset of males with VUS. A more exploratory finding was lack of
      understanding of results among men who underwent GC utilizing video and phone.
      Studies optimizing GC strategies for males undergoing multigene testing for
      inherited PCA are warranted.

PMID- 29655298
TI  - An In Vitro Model of the Blood-Brain Barrier: Naegleria fowleri Affects the Tight
      Junction Proteins and Activates the Microvascular Endothelial Cells.
AB  - Naegleria fowleri causes a fatal disease known as primary amoebic
      meningoencephalitis. This condition is characterized by an acute inflammation
      that originates from the free passage of peripheral blood cells to the central
      nervous system through the alteration of the blood-brain barrier. In this work,
      we established models of the infection in rats and in a primary culture of
      endothelial cells from rat brains with the aim of evaluating the activation and
      the alterations of these cells by N. fowleri. We proved that the rat develops the
      infection similar to the mouse model. We also found that amoebic cysteine
      proteases produced by the trophozoites and the conditioned medium induced
      cytopathic effect in the endothelial cells. In addition, N. fowleri can decrease
      the transendothelial electrical resistance by triggering the destabilization of
      the tight junction proteins claudin-5, occludin, and ZO-1 in a time-dependent
      manner. Furthermore, N. fowleri induced the expression of VCAM-1 and ICAM-1 and
      the production of IL-8, IL-1beta, TNF-alpha, and IL-6 as well as nitric oxide. We
      conclude that N. fowleri damaged the blood-brain barrier model by disrupting the
      intercellular junctions and induced the presence of inflammatory mediators by
      allowing the access of inflammatory cells to the olfactory bulbs.

PMID- 29655299
TI  - Abnormal small bowel motility in patients with hereditary transthyretin
      amyloidosis.
AB  - BACKGROUND: Gastrointestinal complications are common in hereditary transthyretin
      amyloid (ATTRm) amyloidosis. The underlying mechanisms have not been fully
      elucidated, and the patients' small bowel function remains largely unexplored.
      The aim of the present study was to compare the small bowel motility in ATTRm
      amyloidosis patients with that in non-amyloidosis patient controls. METHODS:
      ATTRm amyloidosis patients undergoing evaluation for liver transplantation were
      consecutively investigated with 24-hour duodenojejunal manometry (n = 19). The
      somatostatin analogue octreotide was used to induce fasting motility. Patients
      with age at onset of >=50 years were defined as late-onset cases. For each
      patient, three age- and sex-matched patient controls (n = 57) were selected from
      the total pool of investigated patients. KEY RESULTS: Manometry was judged as
      abnormal in 58% of the patients and in 26% of the patient controls (P = .01).
      Patients displayed significantly more daytime phase III migrating motor complexes
      than patient controls (median 4 vs 2, P < .01), and had a higher frequency of low
      amplitude complexes (16% vs 4%; however, this difference did not reach
      statistical significance, P = .10). Furthermore, late-onset patients showed a
      delay in octreotide response (5.4 vs 3.8 minutes, P < .01), but this was not
      observed for early-onset patients or within the control group. CONCLUSIONS AND
      INFERENCES: Patients with ATTRm amyloidosis displayed abnormalities in their
      small bowel motility more frequently than non-amyloidosis patient controls, and
      the manometric pattern was probably best consistent with a combined
      neuromyopathic disorder. The delayed octreotide response in late-onset patients
      warrants further investigation.

PMID- 29655300
TI  - April 2018 at a glance: focus on prognostic variables.

PMID- 29655301
TI  - Analysis of Human Nuclear Protein Complexes by Quantitative Mass Spectrometry
      Profiling.
AB  - Analysis of protein complexes provides insights into how the ensemble of
      expressed proteome is organized into functional units. While there have been
      advances in techniques for proteome-wide profiling of cytoplasmic protein
      complexes, information about human nuclear protein complexes are very limited. To
      close this gap, we combined native size exclusion chromatography (SEC) with label
      free quantitative MS profiling to characterize hundreds of nuclear protein
      complexes isolated from human glioblastoma multiforme T98G cells. We identified
      1794 proteins that overlapped between two biological replicates of which 1244
      proteins were characterized as existing within stably associated putative
      complexes. co-IP experiments confirmed the interaction of PARP1 with Ku70/Ku80
      proteins and HDAC1 (histone deacetylase complex 1) and CHD4. HDAC1/2 also co
      migrated with various SIN3A and nucleosome remodeling and deacetylase components
      in SEC fractionation including SIN3A, SAP30, RBBP4, RBBP7, and NCOR1. Co-elution
      of HDAC1/2/3 with both the KDM1A and RCOR1 further confirmed that these proteins
      are integral components of human deacetylase complexes. Our approach also
      demonstrated the ability to identify potential moonlighting complexes and novel
      complexes containing uncharacterized proteins. Overall, the results demonstrated
      the utility of SEC fractionation and LC-MS analysis for system-wide profiling of
      proteins to predict the existence of distinct forms of nuclear protein complexes.

PMID- 29655302
TI  - Optically Matched Semiconductor Quantum Dots Improve Photophosphorylation
      Performed by Chloroplasts.
AB  - A natural-artificial hybrid system was constructed to enhance
      photophosphorylation. The system comprises chloroplasts modified with optically
      matched quantum dots (chloroplast-QD) with a large Stokes shift. The QDs possess
      a unique optical property and transform ultraviolet light into available and
      highly effective red light for use by chloroplasts. This favorable feature
      enables photosystem II contained within the hybrid system to split more water and
      produce more protons than chloroplasts would otherwise do on their own.
      Consequently, a larger proton gradient is generated and photophosphorylation is
      improved. At optimal efficiency activity increased by up to 2.3 times compared to
      pristine chloroplasts. Importantly, the degree of overlap between emission of the
      QDs and absorption of chloroplasts exerts a strong influence on the
      photophosphorylation efficiency. The chloroplast-QD hybrid presents an efficient
      solar energy conversion route, which involves a rational combination of a natural
      system and an artificial light-harvesting nanomaterial.

PMID- 29655303
TI  - Reductive Elimination Leading to C-C Bond Formation in Gold(III) Complexes: A
      Mechanistic and Computational Study.
AB  - The factors affecting the rates of reductive C-C cross-coupling reactions in
      gold(III) aryls were studied by using complexes that allow easy access to a
      series of electronically modified aryl ligands, as well as to gold methyl and
      vinyl complexes, by using the pincer compounds [(C^N^C)AuR] (R=C6 F5 , CH=CMe2 ,
      Me and p-C6 H4 X, where X=OMe, F, H, tBu, Cl, CF3 , or NO2 ) as starting
      materials (C^N^C=2,6-(4'-tBuC6 H3 )2 pyridine dianion). Protodeauration followed
      by addition of one equivalent SMe2 leads to the quantitative generation of the
      thioether complexes [(C^N-CH)AuR(SMe2 )]+ . Upon addition of a second SMe2
      pyridine is displaced, which triggers the reductive aryl-R elimination. The rates
      for these cross-couplings increase in the sequence k(vinyl)>k(aryl)?k(C6 F5
      )>k(Me). Vinyl-aryl coupling is particularly fast, 1.15*10-3  L mol-1  s-1 at 221
      K, whereas both C6 F5 and Me couplings encountered higher barriers for the C-C
      bond forming step. The use of P(p-tol)3 in place of SMe2 greatly accelerates the
      C-C couplings. Computational modelling shows that in the C^N-bonded compounds
      displacement of N by a donor L is required before the aryl ligands can adopt a
      conformation suitable for C-C bond formation, so that elimination takes place
      from a four-coordinate intermediate. The C-C bond formation is the rate-limiting
      step. In the non-chelating case, reductive C(sp2 )-C(sp2 ) elimination from three
      coordinate ions [(Ar1 )(Ar2 )AuL]+ is almost barrier-free, particularly if
      L=phosphine.

PMID- 29655304
TI  - Sb-Doped SnO2 Nanorods Underlayer Effect to the alpha-Fe2 O3 Nanorods Sheathed
      with TiO2 for Enhanced Photoelectrochemical Water Splitting.
AB  - Here, a Sb-doped SnO2 (ATO) nanorod underneath an alpha-Fe2 O3 nanorod sheathed
      with TiO2 for photoelectrochemical (PEC) water splitting is reported. The
      experimental results, corroborated with theoretical analysis, demonstrate that
      the ATO nanorod underlayer effect on the alpha-Fe2 O3 nanorod sheathed with TiO2
      enhances the PEC water splitting performance. The growth of the well-defined ATO
      nanorods is reported as a conductive underlayer to improve alpha-Fe2 O3 PEC water
      oxidation performance. The alpha-Fe2 O3 nanorods grown on the ATO nanorods
      exhibit improved performance for PEC water oxidation compared to alpha-Fe2 O3
      grown on flat fluorine-doped tin oxide glass. Furthermore, a simple and facile
      TiCl4 chemical treatment further introduces TiO2 passivation layer formation on
      the alpha-Fe2 O3 to reduce surface recombination. As a result, these unique
      nanostructures show dramatically improved photocurrent density (139% higher than
      that of the pure hematite nanorods).

PMID- 29655306
TI  - Clay Nanoparticles Elicit Long-Term Immune Responses by Forming Biodegradable
      Depots for Sustained Antigen Stimulation.
AB  - Nanomaterials have been widely tested as new generation vaccine adjuvants, but
      few evoke efficient immunoreactions. Clay nanoparticles, for example, layered
      double hydroxide (LDH) and hectorite (HEC) nanoparticles, have shown their potent
      adjuvanticity in generating effective and durable immune responses. However, the
      mechanism by which clay nanoadjuvants stimulate the immune system is not well
      understood. Here, it is demonstrated that LDH and HEC-antigen complexes form
      loose agglomerates in culture medium/serum. They also form nodules with loose
      structures in tissue after subcutaneous injection, where they act as a depot for
      up to 35 d. More importantly, clay nanoparticles actively and continuously
      recruit immune cells into the depot for up to one month, and stimulate stronger
      immune responses than FDA-approved adjuvants, Alum and QuilA. Sustained antigen
      release is also observed in clay nanoparticle depots, with 50-60% antigen
      released after 35 d. In contrast, Alum-antigen complexes show minimal antigen
      release from the depot. Importantly, LDH and HEC are more effective than QuilA
      and Alum in promoting memory T-cell proliferation. These findings suggest that
      both clay nanoadjuvants can serve as active vaccine platforms for sustained and
      potent immune responses.

PMID- 29655307
TI  - The importance of melanoma inhibitory activity gene family in the tumor
      progression of oral cancer.
AB  - Oral squamous cell carcinoma has a high potential for locoregional invasion and
      nodal metastasis. Consequently, early detection of such malignancies is of
      immense importance. The melanoma inhibitory activity (MIA) gene family comprises
      MIA, MIA2, transport and Golgi organization protein 1 (TANGO), and otoraplin
      (OTOR). These members of the MIA gene family have a highly conserved Src homology
      3 (SH3)-like structure. Although the molecules of this family share 34-45% amino
      acid homology and 47-59% cDNA sequence homology, those members, excluding OTOR,
      play different tumor-associated functions. MIA has a pivotal role in the
      progression and metastasis of melanoma; MIA2 and TANGO have been suggested to
      possess tumor-suppressive functions; and OTOR is uniquely expressed in cochlea of
      the inner ear. Therefore, the definite functions of the MIA gene family in cancer
      cells remain unclear. Since the members of the MIA gene family are secreted
      proteins, these molecules might be useful tumor markers that can be detected in
      the body fluids, including serum and saliva. In this review, we described the
      molecular biological functions of the MIA gene family in oral cancer.

PMID- 29655308
TI  - Sleep as therapy in neurodevelopmental disorders.

PMID- 29655309
TI  - Together We are Stronger: challenges of post-Soviet healthcare.

PMID- 29655310
TI  - The Effect of Zn(II) Ions and Reactive Oxygen on the Uptake of Zinc and
      Production of Carotenoids by Selected Red Yeasts.
AB  - Three strains of red yeast Rhodosporidium kratochvilovae, Rhodotorula glutinis
      and Sporidiobolus salmonicolor were studied for their responses to the presence
      metal stress, oxidative stress and a combination of these stress factors. For all
      yeast strains, the production of beta-carotene increased in stress conditions.
      The combination of H2 O2 and Zn2+ significantly activated the pathways for the
      production of torularhodin in the strain R. glutinis (from 250 to 470 MUg g-1
      DCW) as well as beta-carotene (from 360 to 1100 MUg g-1 DCW) and torulene (from
      100 to 360 MUg g-1 DCW) in Sp. salmonicolor. Strains of R. glutinis and Rh.
      kratochvilovae bound the majority of Zn(II) ions to the fibrillar part of the
      cell walls, whereas the strain Sp. salmonicolor bound them to both extracellular
      polymers and the fibrillar part of the cell walls. A decrease in the ability of
      yeasts to tolerate higher concentrations of Zn(II) in the presence of free
      radicals (hydrogen peroxide) was also found.

PMID- 29655311
TI  - Fosphenytoin for control of electrical storm in acute myocardial infarction and
      Purkinje fiber-mediated arrhythmias.
AB  - BACKGROUND: Purkinje fiber-mediated arrhythmias in the setting of acute
      myocardial infarction are poorly responsive to conventional antiarrhythmic
      therapy, increases overall mortality and often requires radiofrequency ablation
      (RFA) for control. In this study, we report the use of intravenous Fosphenytoin
      for the control of arrhythmic storm in patients with acute myocardial infarction.
      METHODS AND RESULTS: Six patients with acute myocardial infarction (5 AW/1 LW)
      and Purkinje-triggered ventricular arrhythmias refractory to conventional
      antiarrhythmics were treated with intravenous Fosphenytoin before considering
      RFA. Arrhythmia control was obtained in all patients after the initial bolus
      dose. Breakthrough episodes were seen in 5/6 within 24-36 hours of the initial
      bolus, necessitating a second bolus. Complete arrhythmia control was obtained in
      all patients within 72 hours and 5/6 patients were successfully discharged from
      the hospital. One patient succumbed to sepsis in hospital while another patient
      succumbed to Sub Dural Hematoma after 3 months. CONCLUSIONS: Intravenous
      Fosphenytoin should be considered before RFA for control of Purkinje fiber
      mediated refractory arrhythmias in acute myocardial infarction patients.

PMID- 29655312
TI  - Porous Nanocomposite Comprising Ultralong Hydroxyapatite Nanowires Decorated with
      Zinc-Containing Nanoparticles and Chitosan: Synthesis and Application in Bone
      Defect Repair.
AB  - Hydroxyapatite nanowires exhibit a great potential in biomedical applications
      owing to their high specific surface area, high flexibility, excellent mechanical
      properties, and similarity to mineralized collagen fibrils of natural bone. In
      this work, zinc-containing nanoparticle-decorated ultralong hydroxyapatite
      nanowires (Zn-UHANWs) with a hierarchical nanostructure have been synthesized by
      a one-step solvothermal method. The highly flexible Zn-UHANWs exhibit a
      hierarchical rough surface and enhanced specific surface area as compared with
      ultralong hydroxyapatite nanowires (UHANWs). To evaluate the potential
      application of Zn-UHANWs in bone regeneration, the biomimetic Zn-UHANWs/chitosan
      (CS) (Zn-UHANWs/CS) composite porous scaffold with 80 wt % Zn-UHANWs was prepared
      by incorporating Zn-UHANWs into the chitosan matrix by the freeze-drying process.
      The as-prepared Zn-UHANWs/CS composite porous scaffold exhibits enhanced
      mechanical properties, highly porous structure, and excellent water retention
      capacity. In addition, the Zn-UHANWs/CS porous scaffold has a good
      biodegradability with the sustainable release of Zn, Ca, and P elements in
      aqueous solution. More importantly, the Zn-UHANWs/CS porous scaffold can promote
      the osteogenic differentiation of rat bone marrow derived mesenchymal stem cells
      and facilitate in vivo bone regeneration as compared with the pure CS porous
      scaffold or UHANWs/CS porous scaffold. Thus, both the Zn-UHANWs and Zn-UHANWs/CS
      porous scaffold developed in this work are promising for application in bone
      defect repair.

PMID- 29655313
TI  - Mitochondrial Genome of Vannella croatica (Amoebozoa, Discosea, Vannellida).
AB  - Mitochondrial genome sequence of Vannella croatica (Amoebozoa, Discosea,
      Vannellida) was obtained using pulse-field gel electrophoretic isolation of the
      circular mitochondrial DNA, followed by the next-generation sequencing. The
      mitochondrial DNA of this species has the length of 28,933 bp and contains 12
      protein-coding genes, two ribosomal RNAs, and 16 transfer RNAs. Vannella croatica
      mitochondrial genome is relatively short compared to other known amoebozoan
      mitochondrial genomes but is rather gene-rich and contains significant number of
      open reading frames.

PMID- 29655314
TI  - Pregnancy outcomes following single and repeat liver transplantation: An
      international 2-center cohort.
AB  - Due to advances in obstetric and transplant medicine, women with a history of
      liver transplantation can have successful pregnancies. However, data on pregnancy
      outcomes is still limited, especially for women who have had a repeat liver
      transplant following graft rejection. This retrospective study compares pregnancy
      outcomes in women with single and repeat liver transplants managed at 2 tertiary
      hospitals in Toronto, Canada and Leuven, Belgium. We identified 41 pregnancies in
      28 transplanted women, 6 of whom conceived following a second liver transplant
      after the first was rejected. Mean maternal age at delivery was 30 +/- 7 years,
      and transplant-to-pregnancy interval was 8.5 +/- 5.1 years. All women had normal
      liver function upon conception. Immunosuppressants included tacrolimus +/-
      azathioprine (n = 26), cyclosporine (n = 4), and prednisone with
      immunosuppressants (n = 11). There were no maternal deaths. Maternal
      complications included hypertensive disorders of pregnancy (n = 10),
      deterioration in renal function (n = 6), gestational diabetes (n = 4), graft
      deterioration (n = 2), and anemia requiring blood transfusion (n = 1).
      Fetal/neonatal adverse outcomes included 2 miscarriages, 3 stillbirths, 1
      neonatal death, 5 small-for-gestational-age infants, and 1 minor congenital
      anomaly. Mean gestational age at delivery was 36.7 +/- 4.2 weeks. There were 14
      (38.9%) preterm births. Outcomes in women with a second transplant were similar
      to those with a single transplant, except for a higher incidence of hypertensive
      disorders. In conclusion, with appropriate multidisciplinary care, stable graft
      function at pregnancy onset, and adherence to immunosuppressive regimens, women
      with single and repeat liver transplants have low rates of graft complications
      but remain at increased risk for pregnancy complications. Immunosuppressants and
      high-dose glucocorticoids can be safely used for maintenance of graft function
      and management of graft deterioration in pregnancy. Liver Transplantation 24 769
      778 2018 AASLD.

PMID- 29655316
TI  - Anomalous surface behavior of hydrated guanidinium ions due to ion pairing.
AB  - Surface affinity of aqueous guanidinium chloride (GdmCl) is compared to that of
      aqueous tetrapropylammonium chloride (TPACl) upon addition of sodium chloride
      (NaCl) or disodium sulfate (Na2SO4). The experimental results have been acquired
      using the surface sensitive technique X-ray photoelectron spectroscopy on a
      liquid jet. Molecular dynamics simulations have been used to produce radial
      distribution functions and surface density plots. The surface affinities of both
      TPA+ and Gdm+ increase upon adding NaCl to the solution. With the addition of
      Na2SO4, the surface affinity of TPA+ increases, while that of Gdm+ decreases.
      From the results of MD simulations it is seen that Gdm+ and SO42- ions form
      pairs. This finding can be used to explain the decreased surface affinity of Gdm+
      when co-dissolved with SO42- ions. Since SO42- ions avoid the surface due to the
      double charge and strong water interaction, the Gdm+-SO42- ion pair resides
      deeper in the solutions' bulk than the Gdm+ ions. Since TPA+ does not form ion
      pairs with SO42-, the TPA+ ions are instead enriched at the surface.

PMID- 29655317
TI  - The control of electron quantum trajectories on the high-order harmonic
      generation of CO and N2 molecules in the presence of a low frequency field.
AB  - In the present work, an efficient method is theoretically investigated for
      extending high-order harmonics and ultrashort attosecond pulse generation in N2
      and CO molecules by using the time-dependent density functional theory approach.
      Our results show that by utilizing chirped laser field in the presence of a low
      frequency field, not only is the harmonic cutoff extended remarkably but also the
      single short quantum trajectory is selected to contribute to the harmonic
      spectra. When a low frequency field is added to the two-color chirped laser
      field, the long quantum trajectories are suppressed and only the short quantum
      trajectories contribute to the higher harmonic emission mechanism. As a result,
      the spectral modulation is significantly decreased and an intense ultrashort
      pulse can be generated from the supercontinuum region of high harmonics. With
      such a scheme, the isolated ultrashort attosecond pulses can be generated in
      length, velocity, and acceleration gauges. Furthermore, these results are
      explained by using the classical and quantum time-frequency analyses.

PMID- 29655318
TI  - Simulations of submonolayer Xe on Pt(111): The case for a chaotic low temperature
      phase.
AB  - Molecular dynamics simulations are reported for the structural and thermodynamic
      properties of submonolayer xenon adsorbed on the (111) surface of platinum for
      temperatures up to the (apparently incipient) triple point and beyond. While the
      motion of the atoms in the surface plane is treated with a standard two
      dimensional molecular dynamics simulation, the model takes into consideration the
      thermal excitation of quantum states associated with surface-normal dynamics in
      an attempt to describe the apparent smoothing of the corrugation with increasing
      temperature. We examine the importance of this thermal smoothing to the relative
      stability of several observed and proposed low-temperature structures. Structure
      factor calculations are compared to experimental results in an attempt to
      determine the low temperature structure of this system. These calculations
      provide strong evidence that, at very low temperatures, the domain wall structure
      of a xenon monolayer adsorbed on a Pt(111) substrate possesses a chaotic-like
      nature, exhibiting long-lived meta-stable states with pinned domain walls, these
      walls having narrow widths and irregular shapes. This result is contrary to the
      standard wisdom regarding this system, namely, that the very low temperature
      phase of this system is a striped incommensurate phase. We present the case for
      further experimental investigation of this and similar systems as possible
      examples of chaotic low temperature phases in two dimensions.

PMID- 29655315
TI  - A 360 degrees  view of circular RNAs: From biogenesis to functions.
AB  - The first circular RNA (circRNA) was identified more than 40 years ago, but it
      was only recently appreciated that circRNAs are common outputs of many eukaryotic
      protein-coding genes. Some circRNAs accumulate to higher levels than their
      associated linear mRNAs, especially in the nervous system, and have clear
      regulatory functions that result in organismal phenotypes. The pre-mRNA splicing
      machinery generates circRNAs via backsplicing reactions, which are often
      facilitated by intronic repeat sequences that base pair to one another and bring
      the intervening splice sites into close proximity. When spliceosomal components
      are limiting, circRNAs can become the preferred gene output, and backsplicing
      reactions are further controlled by exon skipping events and the combinatorial
      action of RNA binding proteins. This allows circRNAs to be expressed in a tissue-
      and stage-specific manner. Once generated, circRNAs are highly stable transcripts
      that often accumulate in the cytoplasm. The functions of most circRNAs remain
      unknown, but some can regulate the activities of microRNAs or be translated to
      produce proteins. Circular RNAs can further interface with the immune system as
      well as control gene expression events in the nucleus, including alternative
      splicing decisions. Circular RNAs thus represent a large class of RNA molecules
      that are tightly regulated, and it is becoming increasingly clear that they
      likely impact many biological processes. This article is categorized under: RNA
      Processing > Splicing Mechanisms RNA Structure and Dynamics > Influence of RNA
      Structure in Biological Systems RNA Evolution and Genomics > RNA and
      Ribonucleoprotein Evolution RNA Evolution and Genomics > Computational Analyses
      of RNA.

PMID- 29655320
TI  - Empirical potential for molecular simulation of graphene nanoplatelets.
AB  - A new empirical potential for layered graphitic materials is reported.
      Interatomic interactions within a single graphene sheet are modeled using a
      Stillinger-Weber potential. Interatomic interactions between atoms in different
      sheets of graphene in the nanoplatelet are modeled using a Lennard-Jones
      interaction potential. The potential is validated by comparing molecular dynamics
      simulations of tensile deformation with the reported elastic constants for
      graphite. The graphite is found to fracture into graphene nanoplatelets when
      subjected to ~15% tensile strain normal to the basal surface of the graphene
      stack, with an ultimate stress of 2.0 GPa and toughness of 0.33 GPa. This force
      field is useful to model molecular interactions in an important class of
      composite systems comprising 2D materials like graphene and multi-layer graphene
      nanoplatelets.

PMID- 29655319
TI  - Molecular dynamics simulations of site point mutations in the TPR domain of
      cyclophilin 40 identify conformational states with distinct dynamic and enzymatic
      properties.
AB  - Cyclophilin 40 (Cyp40) is a member of the immunophilin family that acts as a
      peptidyl-prolyl-isomerase enzyme and binds to the heat shock protein 90 (Hsp90).
      Its structure comprises an N-terminal cyclophilin domain and a C-terminal
      tetratricopeptide (TPR) domain. Cyp40 is overexpressed in prostate cancer and
      certain T-cell lymphomas. The groove for Hsp90 binding on the TPR domain includes
      residues Lys227 and Lys308, referred to as the carboxylate clamp, and is
      essential for Cyp40-Hsp90 binding. In this study, the effect of two mutations,
      K227A and K308A, and their combinative mutant was investigated by performing a
      total of 5.76 MUs of all-atom molecular dynamics (MD) simulations in explicit
      solvent. All simulations, except the K308A mutant, were found to adopt two
      distinct (extended or compact) conformers defined by different cyclophilin-TPR
      interdomain distances. The K308A mutant was only observed in the extended form
      which is observed in the Cyp40 X-ray structure. The wild-type, K227A, and
      combined mutant also showed bimodal distributions. The experimental melting
      temperature, Tm, values of the mutants correlate with the degree of compactness
      with the K308A extended mutant having a marginally lower melting temperature.
      Another novel measure of compactness determined from the MD data, the
      "coordination shell volume," also shows a direct correlation with Tm. In
      addition, the MD simulations show an allosteric effect with the mutations in the
      remote TPR domain having a pronounced effect on the molecular motions of the
      enzymatic cyclophilin domain which helps rationalise the experimentally observed
      increase in enzyme activity measured for all three mutations.

PMID- 29655321
TI  - "Trampoline" ejection of organic molecules from graphene and graphite via keV
      cluster ions impacts.
AB  - We present the data on ejection of molecules and emission of molecular ions
      caused by single impacts of 50 keV C602+ on a molecular layer of deuterated
      phenylalanine (D8Phe) deposited on free standing, 2-layer graphene. The
      projectile impacts on the graphene side stimulate the abundant ejection of intact
      molecules and the emission of molecular ions in the transmission direction. To
      gain insight into the mechanism of ejection, Molecular Dynamic simulations were
      performed. It was found that the projectile penetrates the thin layer of
      graphene, partially depositing the projectile's kinetic energy, and molecules are
      ejected from the hot area around the hole that is made by the projectile. The
      yield, Y, of negative ions of deprotonated phenylalanine, (D8Phe-H)-, emitted in
      the transmission direction is 0.1 ions per projectile impact. To characterize the
      ejection and ionization of molecules, we have performed the experiments on
      emission of (D8Phe-H)- from the surface of bulk D8Phe (Y = 0.13) and from the
      single molecular layer of D8Phe deposited on bulk pyrolytic graphite (Y = 0.15).
      We show that, despite the similar yields of molecular ions, the scenario of the
      energy deposition and ejection of molecules is different for the case of graphene
      due to the confined volume of projectile-analyte interaction. The projectile
      impact on the graphene-D8Phe sample stimulates the collective radial movement of
      analyte atoms, which compresses the D8Phe layer radially from the hole. At the
      same time, this compression bends and stretches the graphene membrane around the
      hole thus accumulating potential energy. The accumulated potential energy is
      transformed into the kinetic energy of correlated movement upward for membrane
      atoms, thus the membrane acts as a trampoline for the molecules. The ejected
      molecules are effectively ionized; the ionization probability is ~30* higher
      compared to that obtained for the bulk D8Phe target. The proposed mechanism of
      ionization involves tunneling of electrons from the vibrationally excited area
      around the hole to the molecules. Another proposed mechanism is a direct proton
      transfer exchange, which is suitable for a bulk target: ions of molecular
      fragments (i.e., CN-) generated in the impact area interact with intact molecules
      from the rim of this area. There is a direct proton exchange process for the
      system D8Phe molecule + CN-.

PMID- 29655322
TI  - Communication: Photoinduced carbon dioxide binding with surface-functionalized
      silicon quantum dots.
AB  - Nowadays, the search for efficient methods able to reduce the high atmospheric
      carbon dioxide concentration has turned into a very dynamic research area.
      Several environmental problems have been closely associated with the high
      atmospheric level of this greenhouse gas. Here, a novel system based on the use
      of surface-functionalized silicon quantum dots (sf-SiQDs) is theoretically
      proposed as a versatile device to bind carbon dioxide. Within this approach,
      carbon dioxide trapping is modulated by a photoinduced charge redistribution
      between the capping molecule and the silicon quantum dots (SiQDs). The chemical
      and electronic properties of the proposed SiQDs have been studied with a Density
      Functional Theory and Density Functional Tight-Binding (DFTB) approach along with
      a time-dependent model based on the DFTB framework. To the best of our knowledge,
      this is the first report that proposes and explores the potential application of
      a versatile and friendly device based on the use of sf-SiQDs for photochemically
      activated carbon dioxide fixation.

PMID- 29655323
TI  - Helium-induced electronic transitions in photo-excited Ba+-Hen exciplexes.
AB  - The possibility for helium-induced electronic transitions in a photo-excited atom
      is investigated using Ba+ excited to the 6p 2P state as a prototypical example. A
      diabatization scheme has been designed to obtain the necessary potential energy
      surfaces and couplings for complexes of Ba+ with an arbitrary number of helium
      atoms. It involves computing new He-Ba+ electronic wave functions and expanding
      them in determinants of the non-interacting complex. The 6p 2P <- 6s 2S
      photodissociation spectrum of He?Ba+ calculated with this model shows very weak
      coupling for a single He atom. However, several electronic relaxation mechanisms
      are identified, which could potentially explain the expulsion of barium ions from
      helium nanodroplets observed experimentally upon Ba+ photoexcitation. For
      instance, an avoided crossing in the ring-shaped He7Ba+ structure is shown to
      provide an efficient pathway for fine structure relaxation. Symmetry breaking by
      either helium density fluctuations or vibrations can also induce efficient
      relaxation in these systems, e.g., bending vibrations in the linear He2Ba+
      excimer. The identified relaxation mechanisms can provide insight into helium
      induced non-adiabatic transitions observed in other systems.

PMID- 29655324
TI  - Instability and thermal conductivity of pressure-densified and elastically
      altered orientational glass of Buckminsterfullerene.
AB  - We report on the temperature, pressure, and time (T, p, and t)-dependent features
      of thermal conductivity, kappa, of partially ordered, non-equilibrium state of
      C60-OG, the orientational glass of Buckminsterfullerene (at T below the
      orientational freezing temperature Tog) made more unstable (i) by partially
      depressurizing its high-p formed state to elastically expand it and (ii) by
      further pressurizing that state to elastically contract it. The sub-Tog effects
      observed on heating of C60-OG differ from those of glasses because phonon
      propagation depends on the ratio of two well-defined orientational states of C60
      molecules and the density of the solid. A broad peak-like feature appears at T
      near Tog in the kappa-T plots of C60-OG formed at 0.7 GPa, depressurized to 0.2
      GPa and heated at 0.2 GPa, which we attribute to partial overlap of the sub-Tog
      and Tog features. A sub-Tog local minimum appears in the kappa-T plots at T well
      below Tog of C60-OG formed at 0.1 GPa, pressurized to 0.5 GPa and heated at 0.5
      GPa and it corresponds to the state of maximum disorder. Although
      Buckminsterfullerene is regarded as an orientationally disordered crystal,
      variation of its properties with T and p is qualitatively different from other
      such crystals. We discuss the findings in terms of the nature of its disorder,
      sensitivity of its rotational dynamics to temperature, and the absence of the
      Johari-Goldstein relaxation. All seem to affect the phenomenology of its glass
      like transition.

PMID- 29655325
TI  - An atomic mean-field spin-orbit approach within exact two-component theory for a
      non-perturbative treatment of spin-orbit coupling.
AB  - An atomic mean-field (AMF) spin-orbit (SO) approach within exact two-component
      theory (X2C) is reported, thereby exploiting the exact decoupling scheme of X2C,
      the one-electron approximation for the scalar-relativistic contributions, the
      mean-field approximation for the treatment of the two-electron SO contribution,
      and the local nature of the SO interactions. The Hamiltonian of the proposed
      SOX2CAMF scheme comprises the one-electron X2C Hamiltonian, the instantaneous two
      electron Coulomb interaction, and an AMF SO term derived from spherically
      averaged Dirac-Coulomb Hartree-Fock calculations of atoms; no molecular
      relativistic two-electron integrals are required. Benchmark calculations for bond
      lengths, harmonic frequencies, dipole moments, and electric-field gradients for a
      set of diatomic molecules containing elements across the periodic table show that
      the SOX2CAMF scheme offers a balanced treatment for SO and scalar-relativistic
      effects and appears to be a promising candidate for applications to heavy-element
      containing systems. SOX2CAMF coupled-cluster calculations of molecular properties
      for bismuth compounds (BiN, BiP, BiF, BiCl, and BiI) are also presented and
      compared with experimental results to further demonstrate the accuracy and
      applicability of the SOX2CAMF scheme.

PMID- 29655326
TI  - Note: Melting criterion for soft particle systems in two dimensions.

PMID- 29655327
TI  - A comparative computational study of coarse-grained and all-atom water models in
      shock Hugoniot states.
AB  - We performed molecular dynamics simulations to study how well some of the water
      models used in simulations describe shocked states. Water in our simulations was
      described using three different models. One was an often-used all-atom TIP4P/2005
      model, while the other two were coarse-grained models used with the MARTINI force
      field: non-polarizable and polarizable MARTINI water. The all-atom model provided
      results in good agreement with Hugoniot curves (for data on pressure versus
      specific volume or, equivalently, on shock wave velocity versus "piston"
      velocity) describing shocked states in the whole range of pressures (up to 11
      GPa) under study. If simulations of shocked states of water using coarse-grained
      models were performed for short time periods, we observed that data obtained for
      shocked states at low pressure were fairly accurate compared to experimental
      Hugoniot curves. Polarizable MARTINI water still provided a good description of
      Hugoniot curves for pressures up to 11 GPa, while the results for the non
      polarizable MARTINI water substantially deviated from the Hugoniot curves. We
      also calculated the temperature of the Hugoniot states and observed that for
      TIP4P/2005 water, they were consistent with those from theoretical calculations,
      while both coarse-grained models predicted much higher temperatures. These high
      temperatures for MARTINI water can be explained by the loss of degrees of freedom
      due to coarse-graining procedure.

PMID- 29655328
TI  - Communication: A coil-stretch transition in planar elongational flow of an
      entangled polymeric melt.
AB  - Virtual experimentation of atomistic entangled polyethylene melts undergoing
      planar elongational flow revealed an amazingly detailed depiction of individual
      macromolecular dynamics and the resulting effect on bistable configurational
      states. A clear coil-stretch transition was evident, in much the same form as
      first envisioned by de Gennes for dilute solutions of high polymers, resulting in
      an associated hysteresis in the configurational flow profile over the range of
      strain rates predicted by theory. Simulations conducted at steady state revealed
      bimodal distribution functions, in which equilibrium configurational states were
      simultaneously populated by relatively coiled and stretched molecules which could
      transition from one conformational mode to the other over a relatively long time
      scale at critical values of strain rates. The implication of such behavior points
      to a double-well conformational free energy potential with an activation barrier
      between the two configurational minima.

PMID- 29655329
TI  - Microsolvation of phthalocyanine molecules in superfluid helium nanodroplets as
      revealed by the optical line shape at electronic origin.
AB  - We investigate the solvent shift of phthalocyanine (Pc) doped into superfluid
      helium droplets and probed by optical spectroscopy at the electronic origin. Our
      present work complements extant studies and provides results that in part
      contradict previous conclusions. In particular, the solvent shift does not
      increase monotonously with droplet radius all the way up to the bulk limit, but
      exhibits just the reverse dependence instead. Moreover, a substructure is
      resolved, whose characteristics depend on the droplet size. This behavior can
      hardly be reconciled with that of a freely rotating Pc-helium complex.

PMID- 29655330
TI  - Investigations of the valence-shell excitations of molecular ethane by high
      energy electron scattering.
AB  - The differential cross sections and generalized oscillator strengths for the low
      lying excitations of the valence-shell 1eg orbital electron in ethane have been
      measured for the first time at a high incident electron energy of 1500 eV and a
      scattering angular range of 1.5 degrees -10 degrees . A weak feature, termed X
      here, with a band center of about 7.5 eV has been observed, which was also
      announced by the previous experimental and theoretical studies. The dynamic
      behaviors of the generalized oscillator strengths for the 3s (8.7 eV), 3s+3p
      (9.31 eV, 9.41 eV), and X (~7.5 eV) transitions on the momentum transfer squared
      have been obtained. The integral cross sections of these transitions from their
      thresholds to 5000 eV have been obtained with the aid of the BE-scaling (B is the
      binding energy and E is the excitation energy) method. The optical oscillator
      strengths of the above transitions determined by extrapolating their generalized
      oscillator strengths to the limit of the squared momentum transfer K2 -> 0 are in
      good agreement with the ones from the photoabsorption spectrum [J. W. Au et al.,
      Chem. Phys. 173, 209 (1993)], which indicates that the present differential cross
      sections, generalized oscillator strengths, and integral cross sections can serve
      as benchmark data.

PMID- 29655331
TI  - Erratum: "Hyperfine interactions and internal rotation in methanol" [J. Chem.
      Phys. 145, 244301 (2016)].

PMID- 29655332
TI  - Water dissociating on rigid Ni(100): A quantum dynamics study on a full
      dimensional potential energy surface.
AB  - We constructed a nine-dimensional (9D) potential energy surface (PES) for the
      dissociative chemisorption of H2O on a rigid Ni(100) surface using the neural
      network method based on roughly 110 000 energies obtained from extensive density
      functional theory (DFT) calculations. The resulting PES is accurate and smooth,
      based on the small fitting errors and the good agreement between the fitted PES
      and the direct DFT calculations. Time dependent wave packet calculations also
      showed that the PES is very well converged with respect to the fitting procedure.
      The dissociation probabilities of H2O initially in the ground rovibrational state
      from 9D quantum dynamics calculations are quite different from the site-specific
      results from the seven-dimensional (7D) calculations, indicating the importance
      of full-dimensional quantum dynamics to quantitatively characterize this gas
      surface reaction. It is found that the validity of the site-averaging
      approximation with exact potential holds well, where the site-averaging
      dissociation probability over 15 fixed impact sites obtained from 7D quantum
      dynamics calculations can accurately approximate the 9D dissociation probability
      for H2O in the ground rovibrational state.

PMID- 29655333
TI  - Relationship between x-ray emission and absorption spectroscopy and the local H
      bond environment in water.
AB  - The connection between specific features in the water X-ray absorption spectrum
      and X-ray emission spectrum (XES) and the local H-bond coordination is studied
      based on structures obtained from path-integral molecular dynamics simulations
      using either the opt-PBE-vdW density functional or the MB-pol force field.
      Computing the XES spectrum using all molecules in a snapshot results in only one
      peak in the lone-pair (1b1) region, while the experiment shows two peaks
      separated by 0.8-0.9 eV. Different H-bond configurations were classified based on
      the local structure index (LSI) and a geometrical H-bond cone criterion. We find
      that tetrahedrally coordinated molecules characterized by high LSI values and two
      strong donated and two strong accepted H-bonds contribute to the low energy 1b1
      emission peak and to the post-edge region in absorption. Molecules with the
      asymmetric H-bond environment with one strong accepted H-bond and one strong
      donated H-bond and low LSI values give rise to the high energy 1b1 peak in the
      emission spectrum and mainly contribute to the pre-edge and main-edge in the
      absorption spectrum. The 1b1 peak splitting can be increased to 0.62 eV by
      imposing constraints on the H-bond length, i.e., for very tetrahedral structures
      short H-bonds (less than 2.68 A) and for very asymmetric structures elongated H
      bonds (longer than 2.8 A). Such structures are present, but underrepresented, in
      the simulations which give more of an average of the two extremes.

PMID- 29655334
TI  - Low-lying excited states by constrained DFT.
AB  - Exploiting the machinery of Constrained Density Functional Theory (CDFT), we
      propose a variational method for calculating low-lying excited states of
      molecular systems. We dub this method eXcited CDFT (XCDFT). Excited states are
      obtained by self-consistently constraining a user-defined population of
      electrons, Nc, in the virtual space of a reference set of occupied orbitals. By
      imposing this population to be Nc = 1.0, we computed the first excited state of
      15 molecules from a test set. Our results show that XCDFT achieves an accuracy in
      the predicted excitation energy only slightly worse than linear-response time
      dependent DFT (TDDFT), but without incurring into problems of variational
      collapse typical of the more commonly adopted DeltaSCF method. In addition, we
      selected a few challenging processes to test the limits of applicability of
      XCDFT. We find that in contrast to TDDFT, XCDFT is capable of reproducing energy
      surfaces featuring conical intersections (azobenzene and H3) with correct
      topology and correct overall energetics also away from the intersection.
      Venturing to condensed-phase systems, XCDFT reproduces the TDDFT solvatochromic
      shift of benzaldehyde when it is embedded by a cluster of water molecules. Thus,
      we find XCDFT to be a competitive method among single-reference methods for
      computations of excited states in terms of time to solution, rate of convergence,
      and accuracy of the result.

PMID- 29655335
TI  - Persistent optical hole-burning spectroscopy of nano-confined dye molecules in
      liquid at room temperature: Spectral narrowing due to a glassy state and
      extraordinary relaxation in a nano-cage.
AB  - Persistent optical hole-burning spectroscopy has been conducted for a dye
      molecule within a very small (~1 nm) reverse micelle at room temperature. The
      spectra show a spectral narrowing due to site-selective excitation. This
      definitely demonstrates that the surroundings of the dye molecule are in a glassy
      state regardless of a solution at room temperature. On the other hand, the hole
      burning spectra exhibit large shifts from excitation frequencies, and their
      positions are almost independent of excitation frequencies. The hole-burning
      spectra have been theoretically calculated by taking account of a vibronic
      absorption band of the dye molecule under the assumption that the surroundings of
      the dye molecule are in a glassy state. The calculated results agree with the
      experimental ones that were obtained for the dye molecule in a polymer glass for
      comparison, where it has been found that the ratio of hole-burning efficiencies
      of vibronic- to electronic-band excitations is quite high. On the other hand, the
      theoretical results do not explain the large spectral shift from the excitation
      frequency and small spectral narrowing observed in the hole-burning spectra
      measured for the dye-containing reverse micelle. It is thought that the spectral
      shift and broadening occur within the measurement time owing to the relaxation
      process of the surroundings that are hot with the thermal energy deposited by the
      dye molecule optically excited. Furthermore, the relaxation should be temporary
      because the cooling of the inside of the reverse micelle takes place with the
      dissipation of the excess thermal energy to the outer oil solvent, and so the
      surroundings of the dye molecule return to the glassy state and do not attain the
      thermal equilibrium. These results suggest that a very small reverse micelle
      provides a unique reaction field in which the diffusional motion can be
      controlled by light in a glassy state.

PMID- 29655336
TI  - A molecular dynamics investigation of the surface tension of water nanodroplets
      and a new technique for local pressure determination through density correlation.
AB  - The surface tension of nanoscale droplets of water was studied with molecular
      dynamics simulations using the BLYPSP-4F water potential. The internal pressure
      of the droplet was measured using an empirical correlation between the pressure
      and density, established through a series of bulk simulations performed at
      pressures from 1 to 1000 bars. Such a procedure allows for reliable determination
      of internal pressure without the need to calculate the local virial. The surface
      tension, estimated with the Young-Laplace relation, shows good agreement with the
      Tolman equation with a Tolman length of -0.48 A. The interface of a liquid water
      droplet is shown to be around 1.1-1.3 nm thick depending on radii. The fairly
      thick interface region puts a lower limit on the size of droplets that still have
      a bulk-like interior.

PMID- 29655337
TI  - Five- and six-electron harmonium atoms: Highly accurate electronic properties and
      their application to benchmarking of approximate 1-matrix functionals.
AB  - Electronic properties of several states of the five- and six-electron harmonium
      atoms are obtained from large-scale calculations employing explicitly correlated
      basis functions. The high accuracy of the computed energies (including their
      components), natural spinorbitals, and their occupation numbers makes them
      suitable for testing, calibration, and benchmarking of approximate formalisms of
      quantum chemistry and solid state physics. In the case of the five-electron
      species, the availability of the new data for a wide range of the confinement
      strengths omega allows for confirmation and generalization of the previously
      reached conclusions concerning the performance of the presently known
      approximations for the electron-electron repulsion energy in terms of the 1
      matrix that are at heart of the density matrix functional theory (DMFT). On the
      other hand, the properties of the three low-lying states of the six-electron
      harmonium atom, computed at omega = 500 and omega = 1000, uncover deficiencies of
      the 1-matrix functionals not revealed by previous studies. In general, the
      previously published assessment of the present implementations of DMFT being of
      poor accuracy is found to hold. Extending the present work to harmonically
      confined systems with even more electrons is most likely counterproductive as the
      steep increase in computational cost required to maintain sufficient accuracy of
      the calculated properties is not expected to be matched by the benefits of
      additional information gathered from the resulting benchmarks.

PMID- 29655338
TI  - Emergence of Landauer transport from quantum dynamics: A model Hamiltonian
      approach.
AB  - The Landauer expression for computing current-voltage characteristics in
      nanoscale devices is efficient but not suited to transient phenomena and a time
      dependent current because it is applicable only when the charge carriers
      transition into a steady flux after an external perturbation. In this article, we
      construct a very general expression for time-dependent current in an electrode
      molecule-electrode arrangement. Utilizing a model Hamiltonian (consisting of the
      subsystem energy levels and their electronic coupling terms), we propagate the
      Schrodinger wave function equation to numerically compute the time-dependent
      population in the individual subsystems. The current in each electrode (defined
      in terms of the rate of change of the corresponding population) has two
      components, one due to the charges originating from the same electrode and the
      other due to the charges initially residing at the other electrode. We derive an
      analytical expression for the first component and illustrate that it agrees
      reasonably with its numerical counterpart at early times. Exploiting the unitary
      evolution of a wavefunction, we construct a more general Landauer style formula
      and illustrate the emergence of Landauer transport from our simulations without
      the assumption of time-independent charge flow. Our generalized Landauer formula
      is valid at all times for models beyond the wide-band limit, non-uniform
      electrode density of states and for time and energy-dependent electronic coupling
      between the subsystems. Subsequently, we investigate the ingredients in our model
      that regulate the onset time scale of this steady state. We compare the
      performance of our general current expression with the Landauer current for time
      dependent electronic coupling. Finally, we comment on the applicability of the
      Landauer formula to compute hot-electron current arising upon plasmon
      decoherence.

PMID- 29655339
TI  - Aqueous solvation of Mg(ii) and Ca(ii): A Born-Oppenheimer molecular dynamics
      study of microhydrated gas phase clusters.
AB  - The hydration features of [Mg(H2O)n]2+ and [Ca(H2O)n]2+ clusters with n = 3-6, 8,
      18, and 27 were studied by means of Born-Oppenheimer molecular dynamics
      simulations at the B3LYP/6-31+G** level of theory. For both ions, it is
      energetically more favorable to have all water molecules in the first hydration
      shell when n <= 6, but stable lower coordination average structures with one
      water molecule not directly interacting with the ion were found for Mg2+ at room
      temperature, showing signatures of proton transfer events for the smaller cation
      but not for the larger one. A more rigid octahedral-type structure for Mg2+ than
      for Ca2+ was observed in all simulations, with no exchange of water molecules to
      the second hydration shell. Significant thermal effects on the average structure
      of clusters were found: while static optimizations lead to compact, spherically
      symmetric hydration geometries, the effects introduced by finite-temperature
      dynamics yield more prolate configurations. The calculated vibrational spectra
      are in agreement with infrared spectroscopy results. Previous studies proposed an
      increase in the coordination number (CN) from six to eight water molecules for
      [Ca(H2O)n]2+ clusters when n >= 12; however, in agreement with recent
      measurements of binding energies, no transition to a larger CN was found when n >
      8. Moreover, the excellent agreement found between the calculated extended X-ray
      absorption fine structure spectroscopy spectra for the larger cluster and the
      experimental data of the aqueous solution supports a CN of six for Ca2+.

PMID- 29655341
TI  - High-resolution infrared spectroscopy of O2H+ in a cryogenic ion trap.
AB  - The protonated oxygen molecule, O2H+, and its helium complex, He-O2H+, have been
      investigated by vibrational action spectroscopy in a cryogenic 22-pole ion trap.
      For the He-O2H+ complex, the frequencies of three vibrational bands have been
      determined by predissociation spectroscopy. The elusive O2H+ has been
      characterized for the first time by high-resolution rovibrational spectroscopy
      via its nu1 OH-stretching band. Thirty-eight rovibrational fine structure
      transitions with partly resolved hyperfine satellites were measured (56 resolved
      lines in total). Spectroscopic parameters were determined by fitting the observed
      lines with an effective Hamiltonian for an asymmetric rotor in a triplet
      electronic ground state, X3A'', yielding a band origin at 3016.73 cm-1. Based on
      these spectroscopic parameters, the rotational spectrum is predicted, but not yet
      detected.

PMID- 29655340
TI  - Communication: Adaptive boundaries in multiscale simulations.
AB  - Combined-resolution simulations are an effective way to study molecular
      properties across a range of length and time scales. These simulations can
      benefit from adaptive boundaries that allow the high-resolution region to adapt
      (change size and/or shape) as the simulation progresses. The number of degrees of
      freedom required to accurately represent even a simple molecular process can vary
      by several orders of magnitude throughout the course of a simulation, and
      adaptive boundaries react to these changes to include an appropriate but not
      excessive amount of detail. Here, we derive the Hamiltonian and distribution
      function for such a molecular simulation. We also design an algorithm that can
      efficiently sample the boundary as a new coordinate of the system. We apply this
      framework to a mixed explicit/continuum simulation of a peptide in solvent. We
      use this example to discuss the conditions necessary for a successful
      implementation of adaptive boundaries that is both efficient and accurate in
      reproducing molecular properties.

PMID- 29655342
TI  - Unraveling the electronic relaxation dynamics in photoexcited 2,4-difluoroaniline
      via femtosecond time-resolved photoelectron imaging.
AB  - Time-resolved photoelectron imaging is employed to investigate the relaxation
      dynamics of the lowest two excited electronic states S1(pipi*) and
      S2(pi3s/pisigma*) in 2,4-difluoroaniline (24DFA). As the S1(pipi*) state is
      populated directly following 289 nm excitation, the population undergoes
      ultrafast intramolecular vibrational redistribution on a 540 fs time scale,
      followed by efficient intersystem crossing from S1(pipi*) to the triplet state
      within 379 ps, and the subsequent slower deactivation process of the triplet
      state. For excitation to the S2(pi3s/pisigma*) state at 238 nm, the population
      probably bifurcates into two decay channels. The dominant channel with 84 fs
      involves ultrafast internal conversion to the S1(pipi*) state, from which it
      relaxes to the electronic ground state on a 116 ps time scale. The other appears
      to involve motion along the S2(pi3s/pisigma*) potential energy surface. Our data
      also determine experimentally the electronic energies of S2(pi3s/pisigma*),
      S3(pipi*), and several Rydberg states in 24DFA.

PMID- 29655343
TI  - Using reweighting and free energy surface interpolation to predict solid-solid
      phase diagrams.
AB  - Many physical properties of small organic molecules are dependent on the current
      crystal packing, or polymorph, of the material, including bioavailability of
      pharmaceuticals, optical properties of dyes, and charge transport properties of
      semiconductors. Predicting the most stable crystalline form at a given
      temperature and pressure requires determining the crystalline form with the
      lowest relative Gibbs free energy. Effective computational prediction of the most
      stable polymorph could save significant time and effort in the design of novel
      molecular crystalline solids or predict their behavior under new conditions. In
      this study, we introduce a new approach using multistate reweighting to address
      the problem of determining solid-solid phase diagrams and apply this approach to
      the phase diagram of solid benzene. For this approach, we perform sampling at a
      selection of temperature and pressure states in the region of interest. We use
      multistate reweighting methods to determine the reduced free energy differences
      between T and P states within a given polymorph and validate this phase diagram
      using several measures. The relative stability of the polymorphs at the sampled
      states can be successively interpolated from these points to create the phase
      diagram by combining these reduced free energy differences with a reference Gibbs
      free energy difference between polymorphs. The method also allows for
      straightforward estimation of uncertainties in the phase boundary. We also find
      that when properly implemented, multistate reweighting for phase diagram
      determination scales better with the size of the system than previously
      estimated.

PMID- 29655344
TI  - Entangled trajectories Hamiltonian dynamics for treating quantum nuclear effects.
AB  - A simple and robust methodology, dubbed Entangled Trajectories Hamiltonian
      Dynamics (ETHD), is developed to capture quantum nuclear effects such as
      tunneling and zero-point energy through the coupling of multiple classical
      trajectories. The approach reformulates the classically mapped second-order
      Quantized Hamiltonian Dynamics (QHD-2) in terms of coupled classical
      trajectories. The method partially enforces the uncertainty principle and
      facilitates tunneling. The applicability of the method is demonstrated by
      studying the dynamics in symmetric double well and cubic metastable state
      potentials. The methodology is validated using exact quantum simulations and is
      compared to QHD-2. We illustrate its relationship to the rigorous Bohmian quantum
      potential approach, from which ETHD can be derived. Our simulations show a
      remarkable agreement of the ETHD calculation with the quantum results, suggesting
      that ETHD may be a simple and inexpensive way of including quantum nuclear
      effects in molecular dynamics simulations.

PMID- 29655345
TI  - The effect of the condensed-phase environment on the vibrational frequency shift
      of a hydrogen molecule inside clathrate hydrates.
AB  - We report a theoretical study of the frequency shift (redshift) of the stretching
      fundamental transition of an H2 molecule confined inside the small dodecahedral
      cage of the structure II clathrate hydrate and its dependence on the condensed
      phase environment. In order to determine how much the hydrate water molecules
      beyond the confining small cage contribute to the vibrational frequency shift,
      quantum five-dimensional (5D) calculations of the coupled translation-rotation
      eigenstates are performed for H2 in the v=0 and v=1 vibrational states inside
      spherical clathrate hydrate domains of increasing radius and a growing number of
      water molecules, ranging from 20 for the isolated small cage to over 1900. In
      these calculations, both H2 and the water domains are treated as rigid. The 5D
      intermolecular potential energy surface (PES) of H2 inside a hydrate domain is
      assumed to be pairwise additive. The H2-H2O pair interaction, represented by the
      5D (rigid monomer) PES that depends on the vibrational state of H2, v=0 or v=1,
      is derived from the high-quality ab initio full-dimensional (9D) PES of the H2
      H2O complex [P. Valiron et al., J. Chem. Phys. 129, 134306 (2008)]. The H2
      vibrational frequency shift calculated for the largest clathrate domain
      considered, which mimics the condensed-phase environment, is about 10% larger in
      magnitude than that obtained by taking into account only the small cage. The
      calculated splittings of the translational fundamental of H2 change very little
      with the domain size, unlike the H2 j = 1 rotational splittings that decrease
      significantly as the domain size increases. The changes in both the vibrational
      frequency shift and the j = 1 rotational splitting due to the condensed-phase
      effects arise predominantly from the H2O molecules in the first three complete
      hydration shells around H2.

PMID- 29655346
TI  - Spatially resolved proton momentum distributions in KDP from first-principles.
AB  - The ferroelectric to paraelectric (PE) phase transition of KH2PO4 (KDP) is
      investigated as a stringent test of the first-principles, normal modes framework
      proposed for calculating anharmonic quantum nuclear motion. Accurate spatially
      resolved momentum distribution functions (MDFs) are directly calculated from the
      nuclear wavefunction, overcoming the limitations of path-integral molecular
      dynamics methods. They indicate coherent, correlated tunneling of protons across
      hydrogen bonds in the PE phase in agreement with neutron Compton scattering data
      and reproduces the key features of the experimental MDF. It further highlights
      the role of Slater's lateral configurations in the PE phase. The analysis in
      terms of normal modes demonstrates the importance of collective, correlated
      proton motion and underlines the value of the employed framework in interpreting
      experimental data. This also makes the framework very attractive for application
      to deuterated KDP to further elucidate the nature of the PE transition and to
      systems exhibiting strong quantum nuclear effects in general.

PMID- 29655347
TI  - Positron scattering from pyridine.
AB  - We present a range of cross section measurements for the low-energy scattering of
      positrons from pyridine, for incident positron energies of less than 20 eV, as
      well as the independent atom model with the screening corrected additivity rule
      including interference effects calculation, of positron scattering from pyridine,
      with dipole rotational excitations accounted for using the Born approximation.
      Comparisons are made between the experimental measurements and theoretical
      calculations. For the positronium formation cross section, we also compare with
      results from a recent empirical model. In general, quite good agreement is seen
      between the calculations and measurements although some discrepancies remain
      which may require further investigation. It is hoped that the present study will
      stimulate development of ab initio level theoretical methods to be applied to
      this important scattering system.

PMID- 29655348
TI  - Mesoscopic electrohydrodynamic simulations of binary colloidal suspensions.
AB  - A model is presented for the solution of electrokinetic phenomena of colloidal
      suspensions in fluid mixtures. We solve the discrete Boltzmann equation with a
      Bhatnagar-Gross-Krook collision operator using the lattice Boltzmann method to
      simulate binary fluid flows. Solvent-solvent and solvent-solute interactions are
      implemented using a pseudopotential model. The Nernst-Planck equation, describing
      the kinetics of dissolved ion species, is solved using a finite difference
      discretization based on the link-flux method. The colloids are resolved on the
      lattice and coupled to the hydrodynamics and electrokinetics through appropriate
      boundary conditions. We present the first full integration of these three
      elements. The model is validated by comparing with known analytic solutions of
      ionic distributions at fluid interfaces, dielectric droplet deformations, and the
      electrophoretic mobility of colloidal suspensions. Its possibilities are explored
      by considering various physical systems, such as breakup of charged and neutral
      droplets and colloidal dynamics at either planar or spherical fluid interfaces.

PMID- 29655349
TI  - Reaction kinetics in open reactors and serial transfers between closed reactors.
AB  - Kinetic theory and thermodynamics of reaction networks are extended to the out-of
      equilibrium dynamics of continuous-flow stirred tank reactors (CSTR) and serial
      transfers. On the basis of their stoichiometry matrix, the conservation laws and
      the cycles of the network are determined for both dynamics. It is shown that the
      CSTR and serial transfer dynamics are equivalent in the limit where the time
      interval between the transfers tends to zero proportionally to the ratio of the
      fractions of fresh to transferred solutions. These results are illustrated with a
      finite cross-catalytic reaction network and an infinite reaction network
      describing mass exchange between polymers. Serial transfer dynamics is typically
      used in molecular evolution experiments in the context of research on the origins
      of life. The present study is shedding a new light on the role played by serial
      transfer parameters in these experiments.

PMID- 29655350
TI  - Decrease in electrical resistivity on depletion of islands of mobility during
      aging of a bulk metal glass.
AB  - The effect of structural relaxation on electrical resistivity, rhoglass, of
      strain-free Zr46.75Ti8.25Cu7.5Ni10Be27.5 bulk metallic glass was studied during
      isothermal aging at several temperatures, Tas. Since cooling of a liquid metal
      increases its resistivity rholiq, one expects rhoglass to increase on aging
      toward rholiq at T = Ta. Instead, rhoglass decreased non-exponentially with the
      aging time. The activation energy of aging kinetics is 189 kJ mol-1, which is
      higher than the activation energy of the Johari-Goldstein (JG) relaxation. After
      considering the sample's contraction, phase separation, and crystallization as
      possible causes of the decrease in rhoglass, we attribute the decrease to
      depletion of islands of atomic mobility, soft spots, or static heterogeneity.
      Vibrations of the atoms in these local (loosely packed) regions and in the
      region's interfacial area contribute to electron scattering. As these deplete on
      aging, the contribution decreases and rhoglass decreases, with a concomitant
      decrease in macroscopic volume, enthalpy, and entropy (V, H, and S). Local
      regions of faster mobility also decrease on cooling as V, H, and S of a liquid
      decrease, but structure fluctuations dominate electron scattering of a liquid
      metal and rholiq increases effectively according to the Ziman-Nagel theory for a
      homogenously disordered structure. Whether depletion of such local regions
      initiates the structural relaxation of a glass, or vice versa, may be resolved by
      finding a glass that physically ages but shows no JG relaxation.

PMID- 29655351
TI  - Force-detected nanoscale absorption spectroscopy in water at room temperature
      using an optical trap.
AB  - Measuring absorption spectra of single molecules presents a fundamental challenge
      for standard transmission-based instruments because of the inherently low signal
      relative to the large background of the excitation source. Here we demonstrate a
      new approach for performing absorption spectroscopy in solution using a force
      measurement to read out optical excitation at the nanoscale. The photoinduced
      force between model chromophores and an optically trapped gold nanoshell has been
      measured in water at room temperature. This photoinduced force is characterized
      as a function of wavelength to yield the force spectrum, which is shown to be
      correlated to the absorption spectrum for four model systems. The instrument
      constructed for these measurements combines an optical tweezer with frequency
      domain absorption spectroscopy over the 400-800 nm range. These measurements
      provide proof-of-principle experiments for force-detected nanoscale
      spectroscopies that operate under ambient chemical conditions.

PMID- 29655352
TI  - Polymer effects on Karman vortex: Molecular dynamics study.
AB  - We investigated the Karman vortex behind a circular cylinder in a polymer
      solution by a molecular dynamics simulation. The vortex characteristics are
      distinctly different for short and long polymers. The solution with the long
      polymer exhibits a reduction in the vortex shedding frequency and broadening of
      the lift coefficient spectrum. On the other hand, the characteristics of the
      short-polymer solution are almost the same as those of the Newtonian fluid. These
      facts are consistent with the experiments. Because the distributions of the
      gyration radius and the orientational order of the long-polymer solution are
      highly inhomogeneous in the flow field, we conclude that the extensional property
      of the polymer plays an important role in changing the flow characteristics.

PMID- 29655353
TI  - Vapor phase nucleation of the short-chain n-alkanes (n-pentane, n-hexane and n
      heptane): Experiments and Monte Carlo simulations.
AB  - We measured the nucleation rates of n-pentane through n-heptane in a supersonic
      nozzle at temperatures ranging from ca. 109 K to 168 K. For n-pentane and n
      hexane, these are the first nucleation rate measurements that have been made, and
      the trends in the current data agree well with those in the earlier work of Ghosh
      et al. [J. Chem. Phys. 132, 024307 (2010)] for longer chain alkanes.
      Complementary Monte Carlo simulations, using the transferable potentials for
      phase equilibria-united atom potentials, suggest that despite the high degree of
      supercooling, the critical clusters remain liquid like under experimental
      conditions for n-pentane through n-heptane, but adopt more ordered structures for
      n-octane and n-nonane. For all three alkanes, the experimental and simulated
      nucleation rates are offset by ~3 orders of magnitude when plotted as a function
      of ln S/(Tc/T - 1)1.5. Explicitly accounting for the surface tension difference
      between the real and model substances, or alternatively using the Hale [Phys.
      Rev. A 33, 4156 (1986); Metall. Mater. Trans. A 23, 1863 (1992)] scaling
      parameter, Omega, consistent with the model potential, increases the offset to ~6
      orders of magnitude.

PMID- 29655354
TI  - Dissociation cross section for high energy O2-O2 collisions.
AB  - Collision-induced dissociation cross section database for high energy O2-O2
      collisions (up to 30 eV) is generated and published using the quasiclassical
      trajectory method on the singlet, triplet, and quintet spin ground state O4
      potential energy surfaces. At equilibrium conditions, these cross sections
      predict reaction rate coefficients that match those obtained experimentally. The
      main advantage of the cross section database based on ab initio computations is
      in the study of complex flows with high degree of non-equilibrium. Direct
      simulation Monte Carlo simulations using the reactive cross section databases are
      carried out for high enthalpy hypersonic oxygen flow over a cylinder at rarefied
      ambient conditions. A comparative study with the phenomenological total collision
      energy chemical model is also undertaken to point out the difference and
      advantage of the reported ab initio reaction model.

PMID- 29655355
TI  - Kinetic effects on the morphology and stability of the pressure-induced extended
      solid of carbon monoxide.
AB  - In this work, the dependence of the morphology and stability of the extended
      solid of carbon monoxide (CO) is correlated to the rate of transformation from
      the molecular CO to extended solid of CO using optical imaging,
      photoluminescence, Raman spectroscopy, and X-ray diffraction. The analyses show
      the rate and pressure of the transformation to be strongly controlled by
      catalytic effects, both chemical and optical. In a larger volume per reaction
      area, the transformation was found to require either a longer time at an elevated
      pressure or a higher pressure compared to a sample synthesized in a smaller
      volume per reaction area, leading to the conclusion that the transformation rate
      is slower for a sample in a larger volume per reaction area. A faster rate of
      transformation was also noted when the reaction area of a CO sample was catalyzed
      with H2SO4. Through variation of the volume per reaction area, pressure or the
      addition of catalysts, it was possible to control the rate of the phase
      transition and therefore the morphology. In general, the extended solid of CO
      synthesized with a faster rate showed a more ordered structure and increased
      metastability relative to the material formed with a slower compression rate.

PMID- 29655356
TI  - High pressure synthesis and stability of cobalt hydrides.
AB  - In situ high-pressure high-temperature X-ray powder diffraction studies of the
      cobalt-hydrogen system reveal the direct synthesis of both the binary cobalt
      hydride (CoH) and a novel cobalt dihydride (CoH2). We observe the formation of
      fcc CoH at pressures of 4 GPa, which persists to pressures of 45 GPa. At this
      pressure, we see the emergence with time of a further expanded fcc lattice, which
      we identify as CoH2, where the hydrogen atoms occupy the tetrahedral vacancies.
      We have explored alternative synthesis routes of CoH2 and can lower the synthesis
      pressure to 35 GPa by the application of high temperature. CoH2 is stable to at
      least 55 GPa and decomposes into CoH below 10 GPa, releasing molecular hydrogen
      before further decomposing completely into its constituent elements below 3 GPa.
      As a first-row transition metal, cobalt has a relatively lower mass than other
      hydride-forming transition metals, and as a result, CoH2 has a high hydrogen
      content of 3.3 wt. % and a volumetric hydrogen density of 214 g/l.

PMID- 29655357
TI  - Soft phonon modes driven huge difference on lattice thermal conductivity between
      topological semimetal WC and WN.
AB  - Topological semimetals are currently attracting increasing interest due to their
      potential applications in topological qubits and low-power electronics, which are
      closely related to their thermal transport properties. Recently, the triply
      degenerate nodal points near the Fermi level of WC are observed by using angle
      resolved photoemission spectroscopy. In this work, by solving the Boltzmann
      transport equation based on first-principles calculations, we systematically
      investigate the phonon transport properties of topological semimetals WC and WN.
      The predicted room-temperature lattice thermal conductivities of WC (WN) along
      the a and c directions are 1140.64 (7.47) W m-1 K-1 and 1214.69 (5.39) W m-1 K-1.
      Considering the similar crystal structure of WC and WN, it is quite interesting
      to find that the thermal conductivity of WC is more than two orders of magnitude
      higher than that of WN. It is found that, different from WN, the large acoustic
      optical (a-o) gap prohibits the acoustic+acoustic -> optical (aao) scattering,
      which gives rise to very long phonon lifetimes, leading to ultrahigh lattice
      thermal conductivity in WC. For WN, the lack of an a-o gap is due to soft phonon
      modes in optical branches, which can provide more scattering channels for aao
      scattering, producing very short phonon lifetimes. Further deep insight can be
      attained from their different electronic structures. Distinctly different from
      that in WC, the density of states of WN at the Fermi level becomes very sharp,
      which leads to destabilization of WN, producing soft phonon modes. It is found
      that the small shear modulus G and C44 limit the stability of WN, compared with
      WC. Our studies provide valuable information for phonon transports in WC and WN,
      and motivate further experimental studies to study their lattice thermal
      conductivities.

PMID- 29655358
TI  - Improving accuracy of electrochemical capacitance and solvation energetics in
      first-principles calculations.
AB  - Reliable first-principles calculations of electrochemical processes require
      accurate prediction of the interfacial capacitance, a challenge for current
      computationally efficient continuum solvation methodologies. We develop a model
      for the double layer of a metallic electrode that reproduces the features of the
      experimental capacitance of Ag(100) in a non-adsorbing, aqueous electrolyte,
      including a broad hump in the capacitance near the potential of zero charge and a
      dip in the capacitance under conditions of low ionic strength. Using this model,
      we identify the necessary characteristics of a solvation model suitable for first
      principles electrochemistry of metal surfaces in non-adsorbing, aqueous
      electrolytes: dielectric and ionic nonlinearity, and a dielectric-only region at
      the interface. The dielectric nonlinearity, caused by the saturation of dipole
      rotational response in water, creates the capacitance hump, while ionic
      nonlinearity, caused by the compactness of the diffuse layer, generates the
      capacitance dip seen at low ionic strength. We show that none of the previously
      developed solvation models simultaneously meet all these criteria. We design the
      nonlinear electrochemical soft-sphere solvation model which both captures the
      capacitance features observed experimentally and serves as a general-purpose
      continuum solvation model.

PMID- 29655359
TI  - Communication: Biological applications of coupled-cluster frozen-density
      embedding.
AB  - We report the implementation of the Laplace-transform scaled opposite-spin (LT
      SOS) resolution-of-the-identity second-order approximate coupled-cluster singles
      and doubles (RICC2) combined with frozen-density embedding for excitation
      energies and molecular properties. In the present work, we furthermore employ the
      Hartree-Fock density for the interaction energy leading to a simplified
      Lagrangian which is linear in the Lagrangian multipliers. This approximation has
      the key advantage of a decoupling of the coupled-cluster amplitude and
      multipliers, leading also to a significant reduction in computation time. Using
      the new simplified Lagrangian in combination with efficient wavefunction models
      such as RICC2 or LT-SOS-RICC2 and density-functional theory (DFT) for the
      environment molecules (CC2-in-DFT) enables the efficient study of biological
      applications such as the rhodopsin and visual cone pigments using ab initio
      methods as routine applications.

PMID- 29655360
TI  - The dependency of adhesion and friction on electrostatic attraction.
AB  - I develop a general mean-field theory for the influence of electrostatic
      attraction between two solids on the contact mechanics. I assume elastic solids
      with random surface roughness. I consider two cases, namely, with and without an
      electrically insulating layer between the conducting solids. The former case is
      important for, e.g., the finger-touch screen interaction. I study how the
      electrostatic attraction influences the adhesion and friction. For the case of an
      insulating layer, I find that when the applied nominal contact pressure is
      relatively small, as the applied voltage increases, there is a sharp increase in
      the contact area, and hence in the friction, at a critical voltage.

PMID- 29655361
TI  - Performance of exchange-correlation functionals in density functional theory
      calculations for liquid metal: A benchmark test for sodium.
AB  - The performance of exchange-correlation functionals in density-functional theory
      (DFT) calculations for liquid metal has not been sufficiently examined. In the
      present study, benchmark tests of Perdew-Burke-Ernzerhof (PBE), Armiento-Mattsson
      2005 (AM05), PBE re-parameterized for solids, and local density approximation
      (LDA) functionals are conducted for liquid sodium. The pair correlation function,
      equilibrium atomic volume, bulk modulus, and relative enthalpy are evaluated at
      600 K and 1000 K. Compared with the available experimental data, the errors range
      from -11.2% to 0.0% for the atomic volume, from -5.2% to 22.0% for the bulk
      modulus, and from -3.5% to 2.5% for the relative enthalpy depending on the DFT
      functional. The generalized gradient approximation functionals are superior to
      the LDA functional, and the PBE and AM05 functionals exhibit the best
      performance. In addition, we assess whether the error tendency in liquid
      simulations is comparable to that in solid simulations, which would suggest that
      the atomic volume and relative enthalpy performances are comparable between solid
      and liquid states but that the bulk modulus performance is not. These benchmark
      test results indicate that the results of liquid simulations are significantly
      dependent on the exchange-correlation functional and that the DFT functional
      performance in solid simulations can be used to roughly estimate the performance
      in liquid simulations.

PMID- 29655362
TI  - Clustering methods for the optimization of atomic cluster structure.
AB  - In this paper, we propose a revised global optimization method and apply it to
      large scale cluster conformation problems. In the 1990s, the so-called clustering
      methods were considered among the most efficient general purpose global
      optimization techniques; however, their usage has quickly declined in recent
      years, mainly due to the inherent difficulties of clustering approaches in large
      dimensional spaces. Inspired from the machine learning literature, we redesigned
      clustering methods in order to deal with molecular structures in a reduced
      feature space. Our aim is to show that by suitably choosing a good set of
      geometrical features coupled with a very efficient descent method, an effective
      optimization tool is obtained which is capable of finding, with a very high
      success rate, all known putative optima for medium size clusters without any
      prior information, both for Lennard-Jones and Morse potentials. The main result
      is that, beyond being a reliable approach, the proposed method, based on the idea
      of starting a computationally expensive deep local search only when it seems
      worth doing so, is capable of saving a huge amount of searches with respect to an
      analogous algorithm which does not employ a clustering phase. In this paper, we
      are not claiming the superiority of the proposed method compared to specific,
      refined, state-of-the-art procedures, but rather indicating a quite
      straightforward way to save local searches by means of a clustering scheme
      working in a reduced variable space, which might prove useful when included in
      many modern methods.

PMID- 29655363
TI  - The structure of PbCl2 on the {100} surface of NaCl and its consequences for
      crystal growth.
AB  - The role that additives play in the growth of sodium chloride is a topic which
      has been widely researched but not always fully understood at an atomic level.
      Lead chloride (PbCl2) is one such additive which has been reported to have growth
      inhibition effects on NaCl {100} and {111}; however, no definitive evidence has
      been reported which details the mechanism of this interaction. In this
      investigation, we used the technique of surface x-ray diffraction to determine
      the interaction between PbCl2 and NaCl {100} and the structure at the surface. We
      find that Pb2+ replaces a surface Na+ ion, while a Cl- ion is located on top of
      the Pb2+. This leads to a charge mismatch in the bulk crystal, which, as
      energetically unfavourable, leads to a growth blocking effect. While this is a
      similar mechanism as in the anticaking agent ferrocyanide, the effect of PbCl2 is
      much weaker, most likely due to the fact that the Pb2+ ion can more easily
      desorb. Moreover, PbCl2 has an even stronger effect on NaCl {111}.

PMID- 29655364
TI  - Incidence and characteristics of low-speed vehicle run over events in rural and
      remote children aged 0-14 years in Queensland: an 11 year (1999-2009)
      retrospective analysis.
AB  - INTRODUCTION: The main objective of this study is to describe incidence rates of
      low-speed vehicle run-over (LSVRO) events among children aged 0-14 years residing
      in Queensland from 1999 to 2009. A second objective was to describe the
      associated patterns of injury, with respect to gender, age group, severity,
      characteristics (host, vehicle and environment), and trends over time in relation
      to geographical remoteness. Final results are hoped to inform prevention
      policies. METHODS: In this statewide, retrospective, population-based study, data
      were collected on LSVRO events that occurred among children aged 0-14 years in
      Queensland from 1999 to 2009 from all relevant data sources across the continuum
      of care, and manually linked to obtain the most comprehensive estimate possible
      of the magnitude and nature of LSVRO events to date. Crude incidence rates were
      calculated separately for males and females, for fatal events, non-fatal events
      (hospital admissions and non-admissions, respectively), and for all LSVRO events,
      for each area of geographical remoteness (major cities, inner regional, outer
      regional, remote/very remote). Relative risks and 95% confidence interval were
      calculated, and trends over time were examined. Data on host, injury and event
      characteristics were also obtained to investigate whether these characteristics
      varied between areas of remoteness. RESULTS: Incidence rates were lowest among
      children (0-14 years) living in major cities (13.8/100 000/annum, with the
      highest recorded incidence in outer regional areas (incidence rate =42.5/100
      000/annum). Incidence rates were higher for children residing outside major
      cities for both males and females, for every age group, for each of the 11 years
      of the study, and consequences of LSVRO events were worse. Young children aged 0
      4 years were identified as those most at risk for these events, regardless of
      geographical location. Differences were observed as a function of remoteness
      category in relation to injury characteristics (eg injury type), and host
      characteristics (eg sociodemographic status), but there were no observed
      differences in environmental characteristics (eg time of day, day of week). Heavy
      vehicles such as four-wheel drives, utilities, trucks and tractors were more
      frequently involved in LSVRO events that occurred outside major cities.
      CONCLUSION: The results confirmed that children of all ages and genders residing
      outside of major cities in Queensland are more at risk of being involved in an
      LSVRO incident, and experience more severe consequences compared to children in
      major cities. Future research should address the specific risk factors and focus
      on engaging rural communities to assist in the prevention of LSVRO incidents.

PMID- 29655365
TI  - Facilitators of community participation in an Aboriginal sexual health promotion
      initiative.
AB  - INTRODUCTION: Community participation is a collaborative process aimed at
      achieving community-identified outcomes. However, approaches to community
      participation within Aboriginal health promotion initiatives have been
      inconsistent and not well documented. Smart and Deadly was a community-led
      initiative to develop sexual health promotion resources with young Aboriginal
      people in regional Victoria, Australia. The principles of community-centred
      practice, authentic participatory processes and respect for the local cultural
      context guided the initiative. The aim of this article is to report factors that
      facilitated community participation undertaken in the Smart and Deadly initiative
      to inform future projects and provide further evidence in demonstrating the value
      of such approaches. METHODS: A summative evaluation of the Smart and Deadly
      initiative was undertaken approximately 2 years after the initiative ended. Five
      focus groups and 13 interviews were conducted with a purposive sample of 32
      participants who were involved with Smart and Deadly in one of the following
      ways: project participant, stakeholder or project partner, or project developer
      or designer. A deductive content analysis was undertaken and themes were compared
      to the YARN model, which was specifically created for planning and evaluating
      community participation strategies relating to Aboriginal sexual health
      promotion. RESULTS: A number of factors that facilitated community participation
      approaches used in Smart and Deadly were identified. The overarching theme was
      that trust was the foundation upon which the facilitators of community
      participation ensued. These facilitators were cultural safety and cultural
      literacy, community control, and legacy and sustainability. Whilst the YARN model
      was highly productive in identifying these facilitators of community
      participation, the model did not have provision for the element of trust between
      workers and community. Given the importance of trust between the project team and
      the Aboriginal community in the Smart and Deadly initiative, a suggested revision
      to the YARN model is that trust is included as the basis upon which YARN model
      factors are predicated. CONCLUSIONS: Adding trust to the YARN model as a basis
      upon which YARN model factors are grounded assists future Aboriginal health
      promotion projects in ensuring community participation approaches are more likely
      to be acceptable to the Aboriginal community.

PMID- 29655366
TI  - HIV-1 protease with leucine zipper fused at N-terminus exhibits enhanced linker
      amino acid-dependent activity.
AB  - BACKGROUND: HIV-1 protease (PR) activation is triggered by Gag-Pol dimerization.
      Premature PR activation results in reduced virion yields due to enhanced Gag
      cleavage. A p6* transframe peptide located directly upstream of protease is
      believed to play a modulating role in PR activation. Previous reports indicate
      that the C-terminal p6* tetra-peptide prevents premature PR activation triggered
      by a leucine zipper (LZ) dimerization motif inserted in the deleted p6* region.
      To clarify the involvement of C-terminal p6* residues in mitigating enhanced LZ
      incurred Gag processing, we engineered constructs containing C-terminal p6*
      residue substitutions with and without a mutation blocking the p6*/PR cleavage
      site, and created other Gag or p6* domain-removing constructs. The capabilities
      of these constructs to mediate virus maturation were assessed by Western blotting
      and single-cycle infection assays. RESULTS: p6*-PR cleavage blocking did not
      significantly reduce the LZ enhancement effect on Gag cleavage when only four
      amino acid residues were present between the p6* and PR. This suggests that the
      potent LZ dimerization motif may enhance PR activation by facilitating PR dimer
      formation, and that PR precursors may trigger sufficient enzymatic activity
      without breaking off from the PR N-terminus. Enhanced LZ-induced activation of PR
      embedded in Gag-Pol was found to be independent of the Gag assembly domain. In
      contrast, the LZ enhancement effect was markedly reduced when six amino acids
      were present at the p6*-PR junction, in part due to impaired PR maturation by
      substitution mutations. We also observed that a proline substitution at the P3
      position eliminated the ability of p6*-deleted Gag-Pol to mediate virus
      maturation, thus emphasizing the importance of C-terminal p6* residues to
      modulating PR activation. CONCLUSIONS: The ability of HIV-1 C-terminal p6* amino
      acid residues to modulate PR activation contributes, at least in part, to their
      ability to counteract enhanced Gag cleavage induced by a leucine zipper
      substituted for a deleted p6*. Changes in C-terminal p6* residues between LZ and
      PR may affect PR-mediated virus maturation, thus providing a possible method for
      assessing HIV-1 protease precursor activation in the context of virus assembly.

PMID- 29655367
TI  - Biologic plating of unstable distal radial fractures.
AB  - BACKGROUND: Volar locking plating through the flexor carpi radialis is a well
      established technique for treating unstable distal radial fractures, with few
      reported complications. In certain circumstances, including metaphyseal
      comminuted fractures, bridge plating through a pronator quadratus (PQ)-sparing
      approach may be required to preserve the soft tissue envelope. This study
      describes our prospective experience with bridge plating through indirect
      reduction. METHODS: Thirty-three wrists (four 23A2, six 23A3, 15 23C1, and eight
      23C2) underwent bridge plating through a PQ-sparing approach with indirect
      reduction from June 2006 to December 2010. Mean patient age was 56.8 years
      (range, 25-83 years), and the mean follow-up period was 47.5 months (range, 36-84
      months). Changes in radiologic parameters (volar tilt, radial inclination, radial
      length, and ulnar variance) were analyzed, and functional results at final follow
      up were evaluated by measuring the Modified Mayo Wrist Score (MMWS) and Modified
      Gartland-Werley Score (MGWS). RESULTS: All wrists achieved bone healing without
      significant complications after a single operation. At final follow-up, radial
      length was restored from an average of 3.7 mm to 11.0 mm, as were radial
      inclination, from 16.4 degrees  to 22.5 degrees , and volar tilt, from - 9.1
      degrees  to 5.5 degrees . However, radial length was overcorrected in three
      wrists, and two experienced residual dorsal tilt. Excellent and good results on
      the MGWS were achieved in 30 wrists (90.9%). The average MMWS outcome was 92.6
      (range, 75-100). CONCLUSION: Our experience with bridge plating was similar to
      that previously reported in the earlier publications. Compared with the
      conventional technique, bridge plating through a PQ-sparing approach may help in
      managing metaphyseal comminuted fractures of both cortices with a reduced radio
      ulnar index.

PMID- 29655368
TI  - Spontaneous posterior rectus sheath hernia: a case report.
AB  - BACKGROUND: Hernias of the posterior rectus sheath are very rare abdominal wall
      hernias with only a handful of cases reported in the literature to date. As an
      uncommon disease, it is important to recognize and report this case in order to
      enhance scientific knowledge of this disease. CASE PRESENTATION: This case report
      presents a spontaneous posterior rectus sheath herniation in a 79-year-old white
      man with previous abdominal surgery for appendicitis. His herniation was
      discovered incidentally during an examination for his chief complaints of lower
      abdominal pain and diarrhea which were later diagnosed as Salmonella-related
      gastroenteritis. A computed tomography scan of his abdomen and pelvis showed
      abdominal wall hernia with loops of small bowel extending into his rectus
      abdominis muscle. In this case, it was decided to leave the situation alone for
      now due to no evidence of bowel obstruction and the low risk of this hernia
      getting strangulated, which otherwise would have warranted urgent surgery.
      CONCLUSIONS: This report adds to the limited stock of available literature on
      this unusual issue and strengthens the evidence base on the best approach to
      support informed clinical decision making. The significant clinical implication
      of such case reports is increased identification rate of rare clinical conditions
      which otherwise often go unnoticed.

PMID- 29655369
TI  - TREM2 regulates innate immunity in Alzheimer's disease.
AB  - Recent research has shown that the triggering receptor expressed on myeloid cells
      2 (TREM2) in microglia is closely related to the pathogenesis of Alzheimer's
      disease (AD). The mechanism of this relationship, however, remains unclear. TREM2
      is part of the TREM family of receptors, which are expressed primarily in myeloid
      cells, including monocytes, dendritic cells, and microglia. The TREM family
      members are cell surface glycoproteins with an immunoglobulin-like extracellular
      domain, a transmembrane region and a short cytoplasmic tail region. The present
      article reviews the following: (1) the structure, function, and variant site
      analysis of the Trem2 gene; (2) the metabolism of TREM2 in peripheral blood and
      cerebrospinal fluid; and (3) the possible underlying mechanism by which TREM2
      regulates innate immunity and participates in AD.

PMID- 29655370
TI  - Descriptive study of severe hospitalized cases of laboratory-confirmed influenza
      during five epidemic seasons (2010-2015).
AB  - OBJECTIVE: The Plan of Information on Acute Respiratory Infections in Catalonia
      (PIDIRAC) included the surveillance of severe hospitalized cases of laboratory
      confirmed influenza (SHCLCI) in 2009. The objective of this study was to
      determine the clinical, epidemiological and virological features of SHCLCI
      recorded in 12 sentinel hospitals during five influenza seasons. RESULTS: From a
      sample of SHCLCI recorded during the 5 influenza epidemics seasons from 2010-2011
      to 2014-2015, Cases were confirmed by PCR and/or viral isolation in cell cultures
      from respiratory samples. A total of 1400 SHCLCI were recorded, 33% required ICU
      admission and 12% died. The median age of cases was 61 years (range 0-101 years);
      70.5% were unvaccinated; 80.4% received antiviral treatment (in 79.6 and 24% of
      cases within 48 h after hospital admission and the onset of symptoms,
      respectively); influenza virus A [37.9% A (H1N1)pdm09, 29.3% A (H3N2)] was
      identified in 87.7% of cases. Surveillance of SHCLCI provides an estimate of the
      severity of seasonal influenza epidemics and the identification and
      characterization of at-risk groups in order to facilitate preventive measures
      such as vaccination and early antiviral treatment.

PMID- 29655371
TI  - Platelet-derived growth factor predicts prolonged relapse-free period in multiple
      sclerosis.
AB  - BACKGROUND: In the early phases of relapsing-remitting multiple sclerosis (RR
      MS), a clear correlation between brain lesion load and clinical disability is
      often lacking, originating the so-called clinico-radiological paradox. Different
      factors may contribute to such discrepancy. In particular, synaptic plasticity
      may reduce the clinical expression of brain damage producing enduring enhancement
      of synaptic strength largely dependent on neurotrophin-induced protein synthesis.
      Cytokines released by the immune cells during acute inflammation can alter
      synaptic transmission and plasticity possibly influencing the clinical course of
      MS. In addition, immune cells may promote brain repair during the post-acute
      phases, by secreting different growth factors involved in neuronal and
      oligodendroglial cell survival. Platelet-derived growth factor (PDGF) is a
      neurotrophic factor that could be particularly involved in clinical recovery.
      Indeed, PDGF promotes long-term potentiation of synaptic activity in vitro and in
      MS and could therefore represent a key factor improving the clinical compensation
      of new brain lesions. The aim of the present study is to explore whether
      cerebrospinal fluid (CSF) PDGF concentrations at the time of diagnosis may
      influence the clinical course of RR-MS. METHODS: At the time of diagnosis, we
      measured in 100 consecutive early MS patients the CSF concentrations of PDGF, of
      the main pro- and anti-inflammatory cytokines, and of reliable markers of
      neuronal damage. Clinical and radiological parameters of disease activity were
      prospectively collected during follow-up. RESULTS: CSF PDGF levels were
      positively correlated with prolonged relapse-free survival. Radiological markers
      of disease activity, biochemical markers of neuronal damage, and clinical
      parameters of disease progression were instead not influenced by PDGF
      concentrations. Higher CSF PDGF levels were associated with an anti-inflammatory
      milieu within the central nervous system. CONCLUSIONS: Our results suggest that
      PDGF could promote a more prolonged relapse-free period during the course of RR
      MS, without influencing inflammation reactivation and inflammation-driven
      neuronal damage and likely enhancing adaptive plasticity.

PMID- 29655373
TI  - The Risk of Adverse Events Related to Extended-Dwell Peripheral Intravenous
      Access.
AB  - Midline catheters (MCs) may be useful to avoid repeated venipuncture in patients
      requiring prolonged intravenous infusions with limited adverse events (AEs). We
      analyzed 2 Italian hospital databases to ascertain the safety of MCs. Among 1,538
      adult patients, 154 MC-related AEs (10%; 2.49 AEs per 1,000 MC days) were
      reported.Infect Control Hosp Epidemiol 2018;875-877.

PMID- 29655374
TI  - Surveying Cystic Fibrosis Care Centers to Assess Adoption of Infection Prevention
      and Control Recommendations.
AB  - OBJECTIVEIn 2013, the Cystic Fibrosis (CF) Foundation developed an updated
      guideline for infection prevention and control (IP&C) practices for CF. We sought
      to assess the adoption of specific recommendations by CF care
      centers.METHODSDirectors of the 277 CF care centers in the United States were
      asked to complete a confidential online survey regarding the adoption of selected
      IP&C recommendations. Selected recommendations were those we considered less
      likely to be incorporated into a center's written IP&C policies.RESULTSCenter
      directors from 198 of 277 CF centers (71%) completed the survey between December
      2015 and June 2016; pediatric and larger centers were more likely to do so.
      Overall, 70% have adopted >=75% of the selected recommendations. As recommended,
      almost all provided education to CF center staff (98%) and patients and families
      (97%); fewer developed educational materials in collaboration with local IP&C
      teams (59%) and/or patients and families (37%). Among 108 centers with non
      English-speaking patients, 65 (60%) provided educational materials in relevant
      languages. Most (74%) held group education events; of the 138 centers with in
      person meetings, 45% allowed 1 individual with CF to attend, and 51% allowed no
      individuals with CF to attend. Most centers (93%) held outdoor events, and 84%
      allowed >1 individual with CF to attend. Audits of exam-room cleaning were
      performed by 49% of CF centers.CONCLUSIONSCystic fibrosis centers in the United
      States have adopted many of the recommendations addressed in this survey.
      Nonetheless, these findings suggest opportunities for improvement. More CF
      centers should provide education to non-English-speaking patients and families,
      and CF centers should perform audits of room cleaning.Infect Control Hosp
      Epidemiol. 2018;39:647-651.

PMID- 29655372
TI  - Population pharmacokinetics/pharmacodynamics of micafungin against Candida
      species in obese, critically ill, and morbidly obese critically ill patients.
AB  - BACKGROUND: Dosing in obese critically ill patients is challenging due to
      pathophysiological changes derived from obesity and/or critical illness, and it
      remains fully unexplored. This study estimated the micafungin probability of
      reaching adequate 24-h area under the curve (AUC0-24h)/minimum inhibitory
      concentration (MIC) values against Candida spp. for an obese/nonobese, critically
      ill/noncritically ill, large population. METHODS: Blood samples for
      pharmacokinetic analyses were collected from 10 critically ill nonobese patients,
      10 noncritically ill obese patients, and 11 critically ill morbidly obese
      patients under empirical/directed micafungin treatment. Patients received once
      daily 100-150 mg micafungin at the discretion of the treating physician following
      the prescribing information and hospital guidelines. Total micafungin
      concentrations were determined by high-performance liquid chromatography (HPLC).
      Monte-Carlo simulations were performed and the probability of target attainment
      (PTA) was calculated using the AUC0-24/MIC cut-offs 285 (C. parapsilosis), 3000
      (all Candida spp.), and 5000 (nonparapsilosis Candida spp.). Intravenous once
      daily 100-mg, 150-mg, and 200-mg doses were simulated at different body weights
      (45, 80, 115, 150, and 185 kg) and age (30, 50, 70 and 90 years old). PTAs >= 90%
      were considered optimal. Fractional target attainment (FTA) was calculated using
      published MIC distributions. A dosing regimen was considered successful if the
      FTA was >= 90%. RESULTS: Overall, 100 mg of micafungin was once-daily
      administered for nonobese and obese patients with body mass index (BMI) <= 45
      kg/m2 and 150 mg for morbidly obese patients with BMI > 45 kg/m2 (except two
      noncritically ill obese patients with BMI ~ 35 kg/m2 receiving 150 mg, and one
      critically ill patient with BMI > 45 kg/m2 receiving 100 mg). Micafungin
      concentrations in plasma were best described using a two-compartment model.
      Weight and age (but not severity score) were significant covariates and improved
      the model. FTAs > 90% were obtained against C. albicans with the 200 mg/24 h dose
      for all body weights (up to 185 kg), and with the 150 mg/24 h for body weights <
      115 kg, and against C. glabrata with the 200 mg/24 h dose for body weights < 115
      kg. CONCLUSION: The lack of adequacy for the 100 mg/24 h dose suggested the need
      to increase the dose to 150 mg/24 h for C. albicans infections. Further
      pharmacokinetic/pharmacodynamic studies should address optimization of micafungin
      dosing for nonalbicans Candida infections.

PMID- 29655375
TI  - Association between traumatic stress load, psychopathology, and cognition in the
      Philadelphia Neurodevelopmental Cohort.
AB  - BACKGROUND: Traumatic stressors during childhood and adolescence are associated
      with psychopathology, mostly studied in the context of post-traumatic stress
      disorder (PTSD) and depression. We investigated broader associations of traumatic
      stress exposure with psychopathology and cognition in a youth community sample.
      METHODS: The Philadelphia Neurodevelopmental Cohort (N = 9498) is an
      investigation of clinical and neurobehavioral phenotypes in a diverse (56%
      Caucasian, 33% African American, 11% other) US youth community population (aged 8
      21). Participants were ascertained through children's hospital pediatric (not
      psychiatric) healthcare network in 2009-2011. Structured psychiatric evaluation
      included screening for lifetime exposure to traumatic stressors, and a
      neurocognitive battery was administered. RESULTS: Exposure rate to traumatic
      stressful events was high (none, N = 5204; one, N = 2182; two, N = 1092; three or
      more, N = 830). Higher stress load was associated with increased psychopathology
      across all clinical domains evaluated: mood/anxiety (standardized beta = .378);
      psychosis spectrum (beta = .360); externalizing behaviors (beta = .311); and fear
      (beta = .256) (controlling for covariates, all p < 0.001). Associations remained
      significant controlling for lifetime PTSD and depression. Exposure to high-stress
      load was robustly associated with suicidal ideation and cannabis use (odds ratio
      compared with non-exposed 5.3 and 3.2, respectively, both p < 0.001). Among
      youths who experienced traumatic stress (N = 4104), history of assaultive trauma
      was associated with greater psychopathology and, in males, vulnerability to
      psychosis and externalizing symptoms. Stress load was negatively associated with
      performance on executive functioning, complex reasoning, and social cognition.
      CONCLUSIONS: Traumatic stress exposure in community non-psychiatric help-seeking
      youth is substantial, and is associated with more severe psychopathology and
      neurocognitive deficits across domains, beyond PTSD and depression.

PMID- 29655376
TI  - Self-reported parental vocabulary input frequency for young children.
AB  - Vocabulary input frequency influences age of acquisition, and is also an
      essential control for investigating the influence of other factors. We propose a
      new method of frequency estimation, self-report. 918 Danish-speaking parents of
      12-36-month-old children estimated their frequency of use of 725 words. Self
      report was substantially correlated with both language sample based frequencies
      (0.67) and frequencies of a large written corpus of Danish (0.58). Correlations
      within vocabulary categories between frequency and age of acquisition, restricted
      to words occurring in the language samples, were comparable for the two
      estimates. Overall, self-report based frequency estimates appear to have a
      promising degree of validity, which reflects their greatest strength,
      independence of the situation.

PMID- 29655377
TI  - Schistosomicidal, antifibrotic and antioxidant effects of Cucurbita pepo L. seed
      oil and praziquantel combined treatment for Schistosoma mansoni infection in a
      mouse model.
AB  - Despite the seriousness of schistosomiasis, its treatment depends only on
      praziquantel (PZQ), which has begun to lose its efficacy against the emergent
      Schistosoma mansoni-resistant strains. Therefore, the discovery of a novel
      schistosomicidal drug is an urgent priority. This study was designed to evaluate
      treatment with Cucurbita pepo L. (pumpkin) seed oil (PSO) alone and combined with
      PZQ against S. mansoni in experimentally infected mice. The study involved five
      groups: GI was the normal control; GII was the infected control; GIII was treated
      with an oral dose of PZQ of 500 mg/kg/day for two successive days, starting in
      the sixth week post infection; GIV was treated with an oral dose of PSO of 50
      mg/kg/day for four weeks, starting in the fourth week post infection; and GV was
      treated with combined PSO-PZQ. Worm burden, tissue egg load and oogram pattern
      were estimated, and the ultrastructure alterations were examined.
      Histopathological examination of granuloma diameters, collagen deposition (Picro
      Sirius red stain), and angiogenesis (immunohistochemical expression of CD34+) was
      conducted and serum liver enzymes were measured to assess the liver condition.
      Moreover, the oxidative stress was evaluated by determining the amounts of
      malondialdehyde and superoxide dismutase in liver homogenates. The results
      revealed significant changes in all the assessed parameters with PSO
      administration. However, PZQ was significantly more effective as an antiparasitic
      agent, whereas PSO was better in terms of fibrosis and oxidative stress. The most
      significant results were obtained in group V, which may be attributed to a
      synergy between PZQ and PSO, with antiparasitic, antioxidant and antifibrotic
      properties.

PMID- 29655378
TI  - Mindfulness-Based Cognitive Therapy v. treatment as usual in adults with ADHD: a
      multicentre, single-blind, randomised controlled trial - ERRATUM.

PMID- 29655379
TI  - Shigella infection in children under 5 years old in western French Guiana.
AB  - French Guiana, a tropical country, is characterised by a young and multi-ethnic
      population. Difficulties in accessing safe water sources lead to outbreaks of
      gastroenteritis. The objectives of this study were (1) to describe the
      microbiological profile of shigella strains isolated in western French Guiana,
      including antimicrobial susceptibility and the distribution of strains in terms
      of species and serotypes and (2) to estimate the incidence of shigellosis in
      children under 5 years old. A retrospective observational study was conducted of
      213 cases of shigellosis diagnosed in the biology department of the hospital
      centre for western French Guiana between 2000 and 2012 in children under 5 years
      old. The serogroups (formerly known as species) that predominates in French
      Guiana was Shigella flexneri. No resistance was observed to fluoroquinolones or
      to third-generation cephalosporins. The average incidence of shigellosis in
      children under 5 years old in western French Guiana was estimated at 189.6 cases
      per 100 000 inhabitants per year. Shigellosis is a public health problem in
      western French Guiana. These infections suggest the difficulties in accessing
      safe water sources and the lack of public sanitation. A quadrivalent vaccine
      containing Shigella sonnei and three serotypes of S. flexneri (S. flexneri 2a, 3a
      and 6) could provide broad coverage against shigella infections.

PMID- 29655380
TI  - Cryoprotectant agents and cooling effect on embryos of Macrobrachium amazonicum.
AB  - SummaryThere are few reports of cryopreservation and injuries in Macrobrachium
      amazonicum embryos. Thus, the aim of this study was to analyze the effects of
      cryoprotectants agents and cooling on stage VIII of this species. Fertilized eggs
      from ovigerous females were removed from the incubation chamber, then placed in
      10 ml Falcon tubes with a cryoprotectant solution and saline-free calcium
      solution. Thus, the embryos underwent a cooling curve of 1 degrees C per min
      until reaching 5 degrees C, and then were stored for 2 h. The tubes containing
      the embryos were washed to remove the cryoprotectant, acclimated for 5 min and
      then transferred to 50 ml incubators. At the end of the 24-h period, living
      embryos from each tube were counted and tabulated. A pool of embryos was fixed
      with 4% formaldehyde and then subjected to histology using 3-mm thick sections
      and stained with haematoxylin/eosin. Another pool was used for biometric analysis
      in which length, width and volume were analyzed. The cryoprotectants agents used
      were: dimethylsulfoxide (DMSO), methyl alcohol, ethylene glycol at 1, 5 and 10%
      and sucrose (0.5 M). Variance analysis was performed followed by Tukey's honest
      significant difference (HSD) test at 5% significance level. DMSO cryoprotectant
      affected embryo survival the least with rates of 71.8, 36.2 and 0% for
      concentrations of 1, 5 and 10%, respectively. Ethylene glycol caused 100%
      mortality at all the concentrations used. It was not possible to observe the
      interference of cooling and cryoprotectants on embryonic structures in this
      study.

PMID- 29655381
TI  - Do Periarticular Joint Infections Present an Increase in Infection Risk?

PMID- 29655382
TI  - Risk factors for influenza-related complications in children during the 2009/10
      pandemic: a UK primary care cohort study using linked routinely collected data.
AB  - Primary care clinicians have a central role in managing influenza/influenza-like
      illness (ILI) during influenza pandemics. This study identifies risk factors for
      influenza-related complications in children presenting with influenza/ILI in
      primary care. We conducted a cohort study using routinely collected linked data
      from the Clinical Practice Research Datalink on children aged 17 years and
      younger who presented with influenza/ILI during the 2009/10 pandemic. We
      calculated odds ratios (ORs) for potential risk factors in relation to influenza
      related complications, complications requiring intervention, pneumonia, all-cause
      hospitalisation and hospitalisation due to influenza-related complications within
      30 days of presentation. Analyses were adjusted for potential confounders
      including age, vaccination and socio-economic deprivation. Asthma was a risk
      factor for influenza-related complications (adjusted OR 1.48, 95% confidence
      interval (CI) 1.21-1.80, P < 0.001), complications requiring intervention
      (adjusted OR 1.44, 95% CI 1.11-1.88; P = 0.007), pneumonia (adjusted OR 1.64, 95%
      CI 1.07-2.51, P = 0.024) and hospitalisation due to influenza-related
      complications (adjusted OR 2.46, 95% CI 1.09-5.56, P = 0.031). Neurological
      conditions were risk factors for all-cause hospitalisation (adjusted OR 4.25, 95%
      CI 1.50-12.07, P = 0.007) but not influenza-related complications (adjusted OR
      1.46, 95% CI 0.83-2.56, P = 0.189). Community-based early interventions to
      prevent influenza-related clinical deterioration should therefore be primarily
      targeted at children with asthma and neurological conditions.

PMID- 29655383
TI  - Hospitalisations due to bacterial gastroenteritis: A comparison of surveillance
      and hospital discharge data.
AB  - Studies estimating the human health impact of the foodborne disease often include
      estimates of the number of gastroenteritis hospitalisations. The aims of this
      study were to examine the degree to which hospital discharge data underreport
      hospitalisations due to bacterial gastroenteritis and to estimate the frequency
      of stool sample submission among patients presenting with gastroenteritis. Using
      linked laboratory and hospital discharge data from a healthcare organisation and
      its affiliated hospital, we examined the International Classification of Disease
      (ICD-9-CM) diagnosis codes assigned to hospitalised adults with culture-confirmed
      Campylobacter, Salmonella, or Escherichia coli O157 infections and determined the
      frequency of stool sample submission. Among 138 hospitalised patients with
      culture-confirmed infections, 43% of Campylobacter patients, 56% of Salmonella
      patients and 35% of E. coli O157 patients had that pathogen-specific code listed
      on the discharge record. Among patients without their infection listed as a
      diagnosis, 65% were assigned a nonspecific gastroenteritis code. Submitting a
      specimen for culture ?3 days before discharge was significantly associated with
      having the pathogen-specific diagnosis listed. Of 6181 patients assigned a
      nonspecific gastroenteritis code, 69% had submitted a stool sample for bacterial
      culture. This study can be used to understand differences and adjust for the
      underreporting and underdiagnosed of Campylobacter, Salmonella and E. coli O157
      in hospital discharge and surveillance data, respectively.

PMID- 29655384
TI  - HIV prevention strategies and risk of infection: a model-based analysis.
AB  - Risk populations for HIV infections tend to neglect condom use, making
      alternative preventive approaches necessary. Accordingly, we modelled the risk of
      sexual HIV transmission for condom use vs. use of rapid diagnostic test (RDT)
      systems with subsequent exclusion of potential sexual partners with a correctly
      or falsely positive test from unprotected sex with and without the use of HIV pre
      exposure prophylaxis (PrEP) in a bio-statistical approach. We combined a
      previously described model of transmission risk for HIV-exposed individuals with
      a newly suggested model of risk of HIV exposure for sexually active HIV-negative
      individuals. The model was adapted for several stages of infection and different
      strategies of HIV infection prevention.HIV prevention with RDTs can reduce the
      transmission risk by up to 97% compared with having sex without any prevention
      and up to 80% compared with condom use. Nevertheless, RDT-based prevention
      strategies demonstrate a lack of protection in several stages of infection; in
      particular, RNA-based RDT systems may fail under treatment. RDT-based pre
      screening of potential sex partners prior to unprotected sexual contacts
      substantially reduces HIV transmission risk. Combination of different prevention
      strategies is advisable for high-risk groups.

PMID- 29655385
TI  - Pertussis epidemiology in Argentina: TRENDS after the introduction of maternal
      immunisation.
AB  - Data on the impact of the recently recommended maternal pertussis vaccination are
      promising, but still insufficient to universalise this approach. We thus compared
      the epidemiological data prior to the implementation of this vaccination strategy
      in Argentina (2012) with the figures reported after 2012. During that 2010-2016
      period, two outbreaks occurred, one in 2011 and another in 2016. In the former,
      the incidence was 6.9/100 000 inhabitants and the case-fatality rate 2.6%.
      Thereafter, a decline in incidence was detected until 2014. During 2015 and 2016
      an increase in the incidence transpired, but this rise was fortunately not
      accompanied by one in the case fatality ratio. Indeed, in 2016 the case fatality
      ratio was the lowest (0.6%). Moreover, during the 2016 outbreak, the incidence
      (3.9/100 000 inhabitants) and the case severity detected in the most vulnerable
      population (infants 0-2 months) were both lower than those in 2011. Consistent
      with this pattern, in 2016, in the most populated province of Argentina (Buenos
      Aires), the case percentage with laboratory-positive results indicating a high
      number of symptoms (59.1% of the total cases) diminished compared with that
      detected in the 2011 outbreak without maternal immunisation (71.9%). Using the
      mathematical model of pertussis transmission we previously designed, we assessed
      the effect of vaccination during pregnancy on infant incidence. From comparisons
      between the epidemiological data made through calculations, emerged the
      possibility that vaccinating women during pregnancy would benefit the infants
      beyond age 2 months, specifically in the 2-12-month cohort.

PMID- 29655386
TI  - A comparative network analysis of eating disorder psychopathology and co
      occurring depression and anxiety symptoms before and after treatment.
AB  - BACKGROUND: Network analysis is an emerging approach in the study of
      psychopathology, yet few applications have been seen in eating disorders (EDs).
      Furthermore, little research exists regarding changes in network strength after
      interventions. Therefore the present study examined the network structures of ED
      and co-occurring depression and anxiety symptoms before and after treatment for
      EDs. METHOD: Participants from residential or partial hospital ED treatment
      programs (N = 446) completed assessments upon admission and discharge. Networks
      were estimated using regularized Graphical Gaussian Models using 38 items from
      the Eating Disorders Examination-Questionnaire, Quick Inventory of Depressive
      Symptomatology, and State-Trait Anxiety Inventory. RESULTS: ED symptoms with high
      centrality indices included a desire to lose weight, guilt about eating, shape
      overvaluation, and wanting an empty stomach, while restlessness, self-esteem,
      lack of energy, and feeling overwhelmed bridged ED to depression and anxiety
      symptoms. Comparisons between admission and discharge networks indicated the
      global network strength did not change significantly, though symptom severity
      decreased. Participants with denser networks at admission evidenced less change
      in ED symptomatology during treatment. CONCLUSIONS: Findings suggest that
      symptoms related to shape and weight concerns and guilt are central ED symptoms,
      while physical symptoms, self-esteem, and feeling overwhelmed are links that may
      underlie comorbidities in EDs. Results provided some support for the validity of
      network approaches, in that admission networks conveyed prognostic information.
      However, the lack of correspondence between symptom reduction and change in
      network strength indicates that future research is needed to examine network
      dynamics in the context of intervention and relapse prevention.

PMID- 29655387
TI  - Specimens, slips and systems: Daniel Solander and the classification of nature at
      the world's first public museum, 1753-1768.
AB  - The British Museum, based in Montague House, Bloomsbury, opened its doors on 15
      January 1759, as the world's first state-owned public museum. The Museum's
      collection mostly originated from Sir Hans Sloane (1660-1753), whose vast
      holdings were purchased by Parliament shortly after his death. The largest
      component of this collection was objects of natural history, including a
      herbarium made up of 265 bound volumes, many of which were classified according
      to the late seventeenth-century system of John Ray (1627-1705). The 1750s saw the
      emergence of Linnaean binomial nomenclature, following the publication of Carl
      Linnaeus' Species Plantarum (1753) and Systema Naturae (1758). In order to adopt
      this new system for their collections, the Trustees of the British Museum chose
      to employ the Swedish naturalist and former student of Linnaeus, Daniel Solander
      (1733-1782) to reclassify the collection. Solander was ordered to devise a new
      system for classifying and cataloguing Sloane's natural history collection, which
      would allow both Linnaeans and those who followed earlier systems to access it.
      Solander's work was essential for allowing the British Museum to realize its aim
      of becoming a public centre of learning, adapting the collection to reflect the
      diversity of classificatory practices which were existent by the 1760s. This task
      engaged Solander until 1768, when he received an offer from Joseph Banks (1743
      1820) to accompany him on HMS Endeavour to the Pacific.

PMID- 29655388
TI  - The Prevalence of Healthcare-Associated Infections in Mainland China: A
      Systematic Review and Meta-analysis.
AB  - OBJECTIVETo assess the prevalence of healthcare-associated infections (HAIs) in
      mainland China.DESIGNSystematic review and meta-analysis.SETTINGAdults and
      children from secondary and tertiary acute-care hospitals in mainland
      China.METHODSWe searched PubMed, the China National Knowledge Infrastructure, and
      Wan Fang for multicenter point-prevalence surveys of acute-care hospitals in
      mainland China from January 2006 to August 2016. All reports related to HAI,
      using a point-prevalence methodology and published either in English or Chinese
      were eligible.RESULTSIn total, 3,021 publications were identified; 115 were
      eligible for quality assessment and data abstraction. The weighted HAI prevalence
      (95% confidence interval [CI]) overall, in general hospitals, children's
      hospitals, maternal and child health hospitals, and oncology hospitals were 3.12%
      (95% CI, 2.94%-3.29%), 3.02% (95% CI, 2.79%-3.26%), 4.43% (95% CI, 3.39%-5.47%),
      1.88% (95% CI, 1.47%-2.29%), and 3.96% (95% CI, 3.12%-4.79%), respectively. In
      general hospitals, prevalence was highest in adult intensive care units (26.07%;
      95% CI, 23.03%-29.12%), followed by surgery (3.26%; 95% CI, 2.96%-3.57%), and
      internal medicine (3.06%; 95% CI, 2.67%-3.46%). Overall, lower respiratory tract
      infection was the most frequent HAI (24,185, 47.28%), followed by urinary tract
      infection (5,773, 11.29%) and upper respiratory tract infection (5,194, 10.15%).
      Gram-negative bacilli were the most frequently isolated pathogens, and
      Pseudomonas aeruginosa (3,395, 14.91%), and Escherichia coli (2,918, 12.82%) were
      the most common single microorganisms.CONCLUSIONSThis study is the largest
      systematic review on the prevalence of HAI in mainland China. These results
      provide a benchmark for future PPSs and a reference for infection prevention and
      control strategies in mainland China.Infect Control Hosp Epidemiol 2018;39:701
      709.

PMID- 29655389
TI  - Dendrorchis pampae sp. n. (Digenea: Gorgoderidae) from Cynopoecilus melanotaenia
      (Cyprinodontiformes: Cynolebiidae) a killifish from southern Brazil, with an
      emended diagnosis of Dendrorchis.
AB  - A new species of Dendrorchis is described and compared with others in the genus.
      The parasites were found in the swim bladder of the annual killifish Cynopoecilus
      melanotaenia. Hosts were collected from a seasonal wetland in southern Brazil.
      The main characteristics of D. pampae are: genital pore in the intestinal
      bifurcation region elongate and lobed vitellaria uterine loops limited to the
      acetabular region and to the rear end of the body; and wide intestinal caeca. An
      emended diagnosis of the genus Dendrorchis includes the characteristics of the
      new species. This is the first record of an adult digenean in an annual killifish
      from South America.

PMID- 29655390
TI  - Long-term epidemiological dynamics of dengue in Barbados - one of the English
      speaking Caribbean countries.
AB  - Using the dengue surveillance program, we prospectively collected data on all the
      suspected and confirmed cases of dengue in Barbados from 2006 to 2015. Data were
      analysed for demographic, seasonal and temporal dynamics of this disease in this
      country. The overall mean annual incidence rate of suspected and confirmed dengue
      over the study period was 0.49% (range 0.15%-0.99%) and 0.16% (range 0.05%
      0.48%), respectively. There was a significant correlation between the mean
      monthly number of confirmed cases, the mean monthly rainfall and the mean monthly
      relative humidity percentage. Dengue in this population is predominantly an
      infection affecting children and young adults. The median age of the patients
      with both, suspected and confirmed dengue was 25 years and the highest proportion
      of cases was seen in the age group 0-15 years. The annual incidence rates of both
      the suspected and the confirmed cases showed an upward trend during the study
      period and this upward trend was more pronounced among children.

PMID- 29655391
TI  - Incidence and prevalence of bacteriologically confirmed pulmonary tuberculosis
      among adolescents and young adults: a systematic review.
AB  - The burden of tuberculosis (TB) among adolescents and young adults in endemic
      settings is poorly characterised. This study aimed to review published and
      unpublished estimates of the incidence and prevalence of bacteriologically
      confirmed TB among young people aged 10-24 years. We searched PubMed and World
      Health Organization archives for publications and unpublished data from
      population-based epidemiologic studies reporting confirmed pulmonary TB among
      young people, conducted from January 2000 onwards. We identified 27 publications
      and unpublished data from two national surveys, representing a total of 26
      studies in 19 countries. The prevalence of bacteriologically confirmed TB ranged
      from 45 to 799 per 100 000 in the Asia-Pacific region and from 160 to 462 per 100
      000 in African settings. We did not identify any epidemiologic studies of
      confirmed TB among adolescents living with human immunodeficiency virus (HIV).
      Many studies were excluded due to absent or inadequately reported age-specific
      data. Adolescents and young adults living in many endemic settings appear to be
      at substantial risk of developing active TB. There is a pressing need to improve
      the routine reporting of age in epidemiologic studies of TB, and to generate high
      quality epidemiologic data regarding TB among adolescents living with HIV.

PMID- 29655392
TI  - Bacteriophage M13 May Be Used for the Assessment of Viral Transfer during Doffing
      of Ebola-Level Personal Protective Equipment.

PMID- 29655393
TI  - Seasonal influenza among children diagnosed by their guardians: a small pilot
      study in Japan.
AB  - : AimWe aimed to elucidate the accuracy and optimal cut-off point of the self
      diagnosis of influenza and the associated clinical symptoms of children by their
      guardians, compared with those of the rapid influenza diagnostic test (RIDT).
      BACKGROUND: Seasonal influenza is a common outpatient problem during the winter
      season. A paediatric influenza epidemic has socio-economic impacts like temporary
      school closure, school event cancellations, and unscheduled work absences among
      parents. Hence, early identification and assessment of influenza to prevent its
      spread is important from a societal perspective. METHOD: We performed a cross
      sectional observational study in a rural clinic in Japan every winter season from
      December 2013 to March 2016. We retrospectively extracted information from the
      medical records and pre-examination checklists of 24 patients aged <12 years
      (mean age, 5.4 years; men, 54.2%). The data extracted from the medical records
      and pre-examination checklist included the baseline characteristics (age, sex and
      past medical history of influenza), clinical signs and symptoms, diagnosis by
      guardians (%) and RIDT results.FindingsThe optimal cut-off point of the self
      diagnosis of influenza by guardians was 80%, with a sensitivity and specificity
      of 63.6% (95% confidence interval: 30.8-89.1) and 92.3% (64.0-99.8). At a 50% cut
      off point, the sensitivity and specificity were 90.9% (58.7-99.8) and 53.8% (25.1
      80.8). The accuracy of feeling severely sick, as estimated by the guardians
      showed a sensitivity and specificity of 90.9% (58.7-99.8) and 69.2% (38.6-90.9).
      Our study indicates that the diagnosis of seasonal influenza by guardians to
      their children would be useful in the establishment of both confirmatory
      diagnoses when it has high probability above the optimal cut-off point (80%), and
      exclusion diagnosis when it has low probability (50%). Not feeling severely sick,
      estimated by the guardians might be a useful indicator for the exclusion of
      paediatric influenza.

PMID- 29655394
TI  - Weather correlates of Campylobacter prevalence in broilers at slaughter under
      tropical conditions in Sri Lanka.
AB  - Campylobacter is the primary agent of human bacterial gastroenteritis worldwide.
      In contrast to temperate zones, weather effects on Campylobacter prevalence in
      broilers under tropical conditions are under-researched. We examined the
      association between weather and Campylobacter prevalence in slaughtered broilers
      in Sri Lanka, a tropical country with weather variations led by monsoons. Each
      month (October 2009-July 2011), 20-30 broiler batches referring to two semi
      automated slaughterhouses from five Sri Lankan provinces were tested for
      Campylobacter contamination and analysed in relation to temperature, humidity and
      rainfall. Overall prevalence was 63.8% (95% CI 59.6-67.9%, n = 542), peaking in
      September-November. Each 1  degrees C increase in monthly mean temperature up to
      26  degrees C increased Campylobacter-positive batches by 16.4% (95% CI 0.4
      35.1%). For each 10 mm increase in monthly total rainfall up to 300 mm,
      Campylobacter-positive batches increased significantly by 0.8% (0.1-1.5%) at 1
      month lag. For each 1% increase in relative humidity up to 80% at 1- and 2-month
      lags, Campylobacter-positive batches increased of respectively 4.2% (1.9-6.7%)
      and 4.0% (1.5-6.5), and decreased by 3.6% (2.6-4.6%) and 4.0% (2.6-5.4%) for unit
      increases above 80%. These results suggest that even in tropical countries
      without marked seasons, there are weather effects possibly reflecting
      Campylobacter potential to colonise its preferred host and/or survive in the
      environment.

PMID- 29655395
TI  - Firearm-related injuries among Canadian children and youth from 2006 to 2013: A
      CHIRPP study.
AB  - CLINICIAN'S CAPSULE What is known about the topic? Injuries from non-powder
      firearms are common and potentially life-altering. The Canadian Pediatric Society
      urges stricter controls on non-powder guns. What did this study ask? What are the
      Canadian contextual trends in paediatric firearm injuries? What did this study
      find? In this study, the rate of paediatric firearm injuries was stable from 2006
      to 2013. Eye injuries inflicted by non-powder firearms were most common. Most
      firearm injuries occurred through recreation and sport. Why does this study
      matter to clinicians? Parents who receive physician counselling about firearm
      safety report change in practice. This study highlights settings/individuals that
      may be appropriate targets for intervention.

PMID- 29655396
TI  - Are lateral ankle injuries in children fractures or sprains?
AB  - Clinical questionWhat is the prevalence of Salter-Harris type I distal fibula
      fractures in children with lateral ankle injuries?Article chosenBoutis K, Plint
      A, Stimec J, et al. Radiograph-negative lateral ankle injuries in children occult
      growth plate fracture or sprain? JAMA Pediatr 2016;170(1):e154114.

PMID- 29655397
TI  - Team composition and chronic disease management within primary healthcare
      practices in eastern Ontario: an application of the Measuring Organizational
      Attributes of Primary Health Care Survey.
AB  - BACKGROUND: Various organizational-level attributes are being implemented in
      primary healthcare to improve healthcare delivery. There is a need to describe
      the distribution and nature of these attributes and explore differences across
      practices.AimThe aim of this study was to better understand organizational
      attributes of primary care teams, focusing specifically on team composition,
      nursing roles, and strategies that support chronic disease management. METHODS:
      We employed a cross-sectional survey design. Team composition, nursing roles,
      availability of health services, and chronic disease management activities were
      described using the 'Measuring Organizational Attributes of Primary Health Care
      Survey.'FindingsA total of 76% (n=26 out of 34) of practice locations completed
      the survey, including family health teams (FHT; n=21) and community health
      centers (CHC; n=4). Nurse practitioners (NPs) and registered nurses (RNs) were
      the most common non-physician providers, and CHCs had a greater proportion of non
      physician providers than FHTs. There was overlap in roles performed by NPs and
      RNs, and registered practical nurses engaged in fewer roles compared with NPs and
      RNs. A greater proportion of FHTs had systematic chronic disease management
      services for hypertension, depression and Alzheimer's disease compared with CHC
      practices. The 'Measuring Organizational Attributes of Primary Health Care
      Survey' was a useful tool to highlight variability in organizational attributes
      across PHC practices. Nurses are prominent within PHC practices, engaging in a
      wide range of roles related to chronic disease management, suggesting a need to
      better understand their contributions to patient care to optimize their roles.

PMID- 29655398
TI  - Adult Empathy: Possible Gender Differences in Gene-Environment Architecture for
      Cognitive and Emotional Components in a Large Italian Twin Sample.
AB  - Empathy plays a central role in prosocial behavior and human cooperation. Very
      few twin researchers have investigated innate and environmental effects in adult
      empathy, and twin research on gender differences in these effects is sparse. The
      goal of this study was to examine innate and environmental influences on three
      components of an empathy scale frequently used with adults - the expression of
      cognitive (CE), emotional (EE), and social skills (SS) empathy - and to explore
      gender differences in the influences. Study participants were ~1,700 twins (18-65
      years) enrolled in the Italian Twin Registry. Empathy was assessed with the
      Italian version of the Empathy Quotient (EQ), for which the three-factor
      structure (i.e., CE, EE, and SS) was confirmed. Twin correlations in monozygotic
      and dizygotic pairs, and males and females were estimated for the total EQ and
      subscale scores, and univariate genetic model fitting was carried out. Women's
      empathy (i.e., total EQ as well as CE and EE subdimensions) was predominantly
      driven by genetic factors and individual experiences, whereas for males, no
      genetic contribution or important shared and individual environmental effects
      emerged. Although of large magnitude, the gender differences did not reach
      statistical significance. Age did not moderate empathy heritability in adulthood.
      Only for the SS subscale were genetic and environmental proportions of variance
      similar for men and women. This study suggests possible gender-specific innate
      and environmental influences on empathy and its cognitive and emotional
      components that need to be confirmed in future studies.

PMID- 29655399
TI  - System outcomes associated with a pediatric emergency department clinical
      decision unit.
AB  - CLINICIAN'S CAPSULE What is known about the topic? Clinical decision units (CDUs)
      may reduce short-stay hospitalizations (<48 hours), which are associated with
      longer lengths of stay, increased staffing needs and higher costs. What did this
      study ask? What are the disposition outcomes and emergency department (ED) return
      rates following CDU care? Has CDU implementation changed short-stay
      hospitalization rates? What did this study find? Most CDU patients were
      discharged, and short-stay hospitalization rate significantly decreased by 0.39%
      with CDU implementation. Why does this study matter to clinicians? The CDU may
      reduce short-stay hospitalizations, and is a safe care option for pediatric
      patients requiring prolonged ED care.

PMID- 29655400
TI  - Seventy years of the British National Health Service: problem, politics and
      policy streams.
AB  - The British National Health Service (NHS) celebrates its 70th birthday on 5 July
      2018. This paper examines this anniversary through the lens of previous
      anniversaries, exploring two strands of political debates and NHS documents. It
      draws on the basic 'multiple streams model' of Kingdon that argues that an issue
      reaches the agenda when the policy window opens to allow the coupling of three
      independent streams - policy, problem and politics. It is found that there
      appears to be some discontinuity in the problem stream; some periods of relative
      consensus and sharp political differences in the politics stream; and sharp
      variations over time in the policy stream. While it is clear that there have been
      both continuities and discontinuities in the problem, politics and policy streams
      over the past 70 years, they have rarely come together to result in a policy that
      has taken it off the agenda.

PMID- 29655401
TI  - Classic, Provocative and/or Influential: A Twin Study Sampler/Twin Research
      Reviews: Twin Pregnancies With and Without Polycystic Ovary Syndrome; Ectopic
      Twin Pregnancy; Sex Differences in Cognition; Maternal Cardiac
      Hemodynamics/Newsworthy: President Obama's Portrait Artist; Winkelvoss Twins
      Update; Triplet Models; 'Meet Your Twin'.
AB  - Selected twin research papers that are classic, provocative, and/or influential
      are surveyed. Many papers meet these criteria, so those chosen reflect the
      opinion of the author. Reviews of recent research on twin pregnancies with and
      without polycystic ovary syndrome, ectopic pregnancy, sex differences in
      cognition and maternal cardiac hemodynamics follow. Newsworthy twin-based items,
      including President Obama's portrait artist, the financial activities of the
      Winkelvoss twins, a set of triplet fashion models and the experience of seeing
      oneself in a painting, are summarized.

PMID- 29655402
TI  - Determining the relationship between bull sperm kinematic subpopulations and
      fluorescence groups using an integrated sperm quality analysis technique.
AB  - The aim of the present study was to determine whether there is an association
      between the kinematic sperm subpopulations and fluorescent groups in bulls using
      a new fluorescent staining method that allows classification of spermatozoa into
      groups depending on their acrosomal and membrane integrity, as well as functional
      status, without inhibiting sperm motility. Cryopreserved semen samples from 10
      Holstein bulls were used in the study. A multiparametric analysis of results
      obtained by the ISAS 3Fun kit (Proiser) was performed. The different fluorescent
      groups were detected and their motility characteristics evaluated using ISAS
      software. Clustering procedures using the kinematic data resulted in the
      classification of spermatozoa into three kinematic sperm subpopulations. The
      distribution of kinematic sperm subpopulations was different between the
      fluorescent sperm groups (P<0.001), although the correlation between them was low
      (r=0.113; P<0.01).

PMID- 29655403
TI  - Lipid profile of bovine blastocysts exposed to insulin during in vitro oocyte
      maturation.
AB  - Insulin is a key hormone with important functions in energy metabolism and is
      involved in the regulation of reproduction. Hyperinsulinaemia is known to impair
      fertility (for example, in obese mothers); therefore, we aimed to investigate the
      impact of elevated insulin concentrations during the sensitive period of oocyte
      maturation on gene expression and lipid profiles of the bovine Day-8 embryo. Two
      different insulin concentrations were used during in vitro oocyte maturation
      (INS10=10ugmL-1 and INS0.1=0.1ugmL-1) in order to observe possible dose-dependent
      effects or thresholds for hyperinsulinaemia in vitro. By investigating gene
      expression patterns by an mRNA microarray in combination with lipid profile
      analysis by desorption electrospray ionisation-mass spectrometry (DESI-MS) of
      embryos derived from insulin-treated oocytes, we gained further insights
      regarding molecular responses of embryos to insulin provocation during the first
      days of development. Lipid metabolism appeared to be influenced on multiple
      levels according to gene expression results but the profiles collected in
      positive-ion mode by DESI-MS (showing mostly ubiquinone, cholesteryl esters and
      triacylglycerols) did not differ significantly from controls. There are parallels
      in follicular development of ruminants and humans that make this bovine model
      relevant for comparative research on early human embryonic development during
      hyperinsulinaemia.

PMID- 29655404
TI  - WITHDRAWN: Treatment Effect of Combination of Nsaid and Antitussives in Patients
      With URTI-Related Cough.
AB  - The Publisher regrets that this article is an accidental duplication of an
      article that has already been published in Eur Respir J. 46 (2015) PA3852,
      http://dx.doi.org/10.1183/13993003.congress-2015.PA3852. The duplicate article
      has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can
      be found at https://www.elsevier.com/about/our-business/policies/article
      withdrawal.

PMID- 29655405
TI  - Special issue on dental research to celebrate KMUD 60th anniversary.

PMID- 29655406
TI  - Aggregatibacter (Actinobacillus) actimycetemcomitans leukotoxin and human
      periodontitis - A historic review with emphasis on JP2.
AB  - Aggregatibacter (Actinobacillus) actimycetemcomitans (Aa) is a gram-negative
      bacterium that colonizes the human oral cavity and is causative agent for
      localized aggressive (juvenile) periodontitis (AgP). In the middle of 1990s, a
      specific JP2 clone of belonging to the cluster of serotype b strains of Aa with
      highly leukotoxicity (leukotoxin, LtxA) able to kill human immune cells was
      isolated. JP2 clone of Aa was strongly associated with in particularly in rapidly
      progressing forms of aggressive periodontitis. The JP2 clone of Aa is transmitted
      through close contacts. Therefore, AgP patients need intense monitoring of their
      periodontal status as the risk for developing severely progressing periodontitis
      lesions are relatively high. Furthermore, timely periodontal treatment, including
      periodontal surgery supplemented by the use of antibiotics, is warranted. More
      importantly, periodontal attachment loss should be prevented by early detection
      of the JP2 clone of Aa by microbial diagnosis testing and/or preventive means.

PMID- 29655407
TI  - Periodontal prosthesis in contemporary dentistry.
AB  - In the last 5 decades, the developments of osseointegrated titanium implants
      (since 1965) have led to the success of contemporary dentistry. Endosseous
      implant-supported restorations delivered in accordance with the traditional
      Branemark protocol have proven to be highly predictable. Today, implants are
      becoming increasingly common in dental care and provide more therapeutic options,
      but treatment planning and the sequencing of therapy are critical in implant
      assisted and implant-supported cases. Implant prostheses give patients and
      dentists more options in treatment planning, but also present challenging
      decisions regarding implant surgery. In essence, the emerging thought is that
      teeth are expendable, as we now have implants to solve these problems. The fact
      that peri-implantitis is no simple problem to treat does not seem to affect many
      who hold that thought. In this article, the authors explain how to properly apply
      the periodontal prosthesis philosophy, concepts, principles, and techniques in
      contemporary dentistry. (This article is an update from the article was published
      in 2005) [1].

PMID- 29655408
TI  - A novel beta-titanium alloy orthodontic wire.
AB  - This literature review investigated a recently developed orthodontic wire
      composed of a beta-titanium alloy known as "Gum Metal" and compared its
      properties with those of conventional wires. The attractive properties of Gum
      Metal include an ultra-low Young's modulus, non-linear elastic behavior, ultra
      high strength, high yield strain, high ductility, and superplastic deformability
      without work hardening at room temperature. The unique multifunctional
      characteristics of this new orthodontic wire make it almost ideal for orthodontic
      applications. The results of this literature review indicate the strong potential
      use of Gum Metal wire for improving and enhancing the effectiveness of
      orthodontic treatment.

PMID- 29655409
TI  - Orthodontic tooth movement: The biology and clinical implications.
AB  - Orthodontic tooth movement relies on coordinated tissue resorption and formation
      in the surrounding bone and periodontal ligament. Tooth loading causes local
      hypoxia and fluid flow, initiating an aseptic inflammatory cascade culminating in
      osteoclast resorption in areas of compression and osteoblast deposition in areas
      of tension. Compression and tension are associated with particular signaling
      factors, establishing local gradients to regulate remodeling of the bone and
      periodontal ligament for tooth displacement. Key regulators of inflammation and
      tissue turnover include secreted factors like RANK ligand and osteoprotegerin,
      transcription factors such as RUNX2 and hypoxia-inducible factor, cytokines,
      prostaglandins, tissue necrosis factors, and proteases, among others.
      Inflammation occurred during tooth movement needs to be well controlled, as
      dysregulated inflammation leads to tissue destruction manifested in orthodontic
      induced root resorption and periodontal disease. Understanding the biology has
      profound clinical implications especially in the area of accelerating orthodontic
      tooth movement. Surgical, pharmacological, and physical interventions are being
      tested to move teeth faster to reduce treatment times and time-dependent adverse
      outcomes. Future developments in acceleratory technology and custom appliances
      will allow orthodontic tooth movement to occur more efficiently and safely.

PMID- 29655410
TI  - Non-orthodontic intervention and non-nutritive sucking behaviours: A literature
      review.
AB  - Anterior open bite (AOB) is one of the most complex malocclusions to manage. AOB
      is caused by either by skeletal, genetic or environmental factors. Numerous
      treatment options are currently utilised to manage AOB. These vary from non
      invasive behavioural shaping to orthodontic and surgical interventions. This
      paper reviews the available orthodontic and non-orthodontic interventions used in
      the management of AOB. The literature review was carried out using the PubMed
      search engine from the first of January 2000 to the first of June 2017. Two major
      keywords (open bite and anterior open bite) were used in addition to 23 minor
      keywords in the review. AOB is one of the most complex malocclusions to treat
      with high relapse rates. Long term outcome in treatments of patients with AOB was
      substantially low. Relapse rates were not taken into consideration for some of
      the literature reviewed. Despite limitations of the literature, it is recommended
      that orofacial myofunctional therapy (OMT) and non-orthodontic intervention (NOI)
      be used in conjunction as an effective treatment option for Anterior Open Bite.

PMID- 29655411
TI  - Functional disorders of the temporomandibular joints: Internal derangement of the
      temporomandibular joint.
AB  - Temporomandibular joint (TMJ) is one of the most complex joints of the human
      body. Due to its unique movement, in terms of combination of rotation and
      translator movement, disc of the joint plays an important role to maintain its
      normal function. In order to sustain the normal function of the TMJ, disc must be
      kept in proper position as well as maintain normal shape in all circumstances.
      Once the disc is not any more in its normal position during function of the
      joint, disturbance of the joint can be occurred which will lead to subsequent
      distortion of the disc. Shape of the disc can be influenced by many factors i.e.:
      abnormal function or composition of the disc itself. Etiology of the internal
      derangement of the disc remains controversial. Multifactorial theory has been
      postulated in most of previous manuscripts. Disc is composed of mainly
      extracellular matrix. Abnormal proportion of collagen type I & III may also leads
      to joint hypermobility which may be also a predisposing factor of this disorder.
      Thus it can be recognized as local manifestation of a systemic disorder.
      Different treatment modalities with from conservative treatment to surgical
      intervention distinct success rate have been reported. Recently treatment with
      extracellular matrix injection becomes more and more popular to strengthen the
      joint itself. Since multifactorial in character, the best solution of the
      treatment modalities should be aimed to resolve possible etiology from different
      aspects. Team work may be indication to reach satisfied results.

PMID- 29655412
TI  - Dental deafferentation and brain damage: A review and a hypothesis.
AB  - In the last few decades, neurobiological and human brain imaging research have
      greatly advanced our understanding of brain mechanisms that support perception
      and memory, as well as their function in daily activities. Knowledge of the
      neurobiological mechanisms behind the deafferentation of stomatognathic systems
      has also expanded greatly in recent decades. In particular, current studies
      reveal that the peripheral deafferentations of stomatognathic systems may be
      projected globally into the central nervous system (CNS) and become an associated
      critical factor in triggering and aggravating neurodegenerative diseases. This
      review explores basic neurobiological mechanisms associated with the
      deafferentation of stomatognathic systems. Further included is a discussion on
      tooth loss and other dental deafferentation (DD) mechanisms, with a focus on
      dental and masticatory apparatuses associated with brain functions and which may
      underlie the changes observed in the aging brain. A new hypothesis is presented
      where DD and changes in the functionality of teeth and the masticatory apparatus
      may cause brain damage as a result of altered cerebral circulation and
      dysfunctional homeostasis. Furthermore, multiple recurrent reorganizations of the
      brain may be a triggering or contributing risk factor in the onset and
      progression of neurodegenerative conditions such as Alzheimer's disease (AD). A
      growing understanding of the association between DD and brain aging may lead to
      solutions in treating and preventing cognitive decline and neurodegenerative
      diseases.

PMID- 29655414
TI  - Augmented reality (AR) and virtual reality (VR) applied in dentistry.
AB  - The OSCE is a reliable evaluation method to estimate the preclinical examination
      of dental students. The most ideal assessment for OSCE is used the augmented
      reality simulator to evaluate. This literature review investigated a recently
      developed in virtual reality (VR) and augmented reality (AR) starting of the
      dental history to the progress of the dental skill. As result of the lacking of
      technology, it needs to depend on other device increasing the success rate and
      decreasing the risk of the surgery. The development of tracking unit changed the
      surgical and educational way. Clinical surgery is based on mature education. VR
      and AR simultaneously affected the skill of the training lesson and navigation
      system. Widely, the VR and AR not only applied in the dental training lesson and
      surgery, but also improved all field in our life.

PMID- 29655413
TI  - The science and application of IPS e.Max dental ceramic.
AB  - The aim of this paper is to report the state of current literature and
      recommendations for the lithium disilicate glass-ceramic IPS e.Max. The materials
      science, mechanical and optical properties were reviewed. Additionally an
      assessment was conducted of current implementation recommendations and clinical
      outcomes. This paper provides a brief historical overview, summary of the
      findings the findings of current literature, and clinical recommendation for the
      use of IPS e.Max CAD in dental applications.

PMID- 29655415
TI  - Clinicopathological analysis of 232 radicular cysts of the jawbone in a
      population of southern Taiwanese patients.
AB  - This retrospective study aimed to evaluate the clinicopathological features of
      232 cases of radicular cyst (January 2001-December 2016) submitted for
      histopathological examination to Department of Oral Pathology by endodontists in
      our institution. Demographic data including age, gender, affected site, involved
      tooth, and histopathological features, were reviewed. The study population
      comprised 133 females (57.3%) and 99 males (42.7%), with a mean age of 40.5 years
      and an age range of 13-78 years. Two-hundred and one cysts occurred in the
      maxilla (86.7%) and 31 in the mandible (13.3%). Most cases involved the anterior
      teeth of the maxilla (67.2%). The most frequently-involved tooth was the
      maxillary lateral incisor (50.5%). In most cases (228 cases; 98.3%), the cyst was
      lined with nonkeratinized stratified squamous epithelium, with two cases
      containing epithelial lining of the mucoepidermoid epithelium (0.9%) and
      respiratory epithelium (0.9%), respectively. One case (0.4%) revealed epithelial
      dysplasia of the epithelial lining. Hyaline body was seen in two cases (0.9%),
      and Rushton body was noted in seven cases (3.0%). Odontogenic epithelial rest was
      noted in one case (0.4%). Cholesterol clefts (54 cases; 23.3%), foamy histiocytes
      (72 cases; 31.0%), hemosiderins (57 cases; 24.6%), dystrophic calcifications (94
      cases; 40.5%), foreign bodies (44 cases; 19.0%), and bacterial colonies (22
      cases; 9.5%) were also observed. Fifty-three cases (22.8%) showed a mixed acute
      and chronic inflammatory infiltrate, whereas chronic inflammatory infiltrate only
      was noted in 179 cases (77.2%). In summary, the current findings provide a
      valuable source for clinicopathological reference concerning radicular cysts of
      the jawbone.

PMID- 29655416
TI  - Corrigendum to "Energy-weighted dynamical scattering simulations of electron
      diffraction modalities in the scanning electron microscope" Ultramicroscopy 187
      (2018) 98-106.

PMID- 29655417
TI  - Corrigendum to Work Function Characterization of the Directionally Solidified
      LaB6--VB2 Eutectic [Ultramicroscopy 183 (2017) 67-71].

PMID- 29655418
TI  - WITHDRAWN: NSAID and Antitussives in Patients With Upper Respiratory Tract
      Infection-Related Cough: A Good Combination?
AB  - The Publisher regrets that this article is an accidental duplication of an
      article that has already been published in Eur Respir J. 46 (2015) PA3852,
      http://dx.doi.org/10.1183/13993003.congress-2015.PA3852. The duplicate article
      has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can
      be found at https://www.elsevier.com/about/our-business/policies/article
      withdrawal.

PMID- 29655419
TI  - A two dimensional metal-organic framework nanosheets-based fluorescence resonance
      energy transfer aptasensor with circular strand-replacement DNA polymerization
      target-triggered amplification strategy for homogenous detection of antibiotics.
AB  - In the study, a novel two dimensional metal-organic framework (Cu-TCPP
      nanosheets) based fluorescence resonance energy transfer (FRET) aptasensing
      platform was developed for detecting antibiotics. Cu-TCPP nanosheets were
      employed for quenching the background fluorescence and circular strand
      replacement DNA polymerization (CSRP) for signal amplification. To fulfill the
      purpose, we designed an aptamer hairpin probe (HP) whose stem can be opened while
      specifically binding to target. Then the opened HP would bind with the primer.
      Under the action of polymerase, extension reaction was induced to generate double
      stranded DNA (dsDNA), and then the target was released for the next cycle.
      Finally, SYBR Green I (SG) can bind with dsDNA to produce strong fluorescence
      response for quantification of target. It's worth mentioning that the
      fluorescence of HP/SG complex and free SG could be completely quenched by Cu-TCPP
      nanosheets while that of dsDNA/SG complex wouldn't be affected. Thus, the sensor
      produced negligible background signals. It can produce 7.5-fold improved S/N
      compared to a graphene oxide (GO)-based FRET aptasensor. Chloramphenicol (CAP)
      was chosen as the model analyte to demonstrate the feasibility of the sensor
      system. The detection range is broad from 0.001 to 10 ng mL-1 with a detection
      limit down to 0.3 pg mL-1. The proposed assay was label free and can be used in
      homogenous detection which greatly simplifies the complexity of operations. The
      strategy opens a new way to develop sensitive, in-situ and simple assay for
      antibiotics in foods.

PMID- 29655420
TI  - Dual enzyme-free amplification strategy for ultra-sensitive fluorescent detection
      of bisphenol A in water.
AB  - An ultra-sensitive strategy for bisphenol A (BPA) detection based on dual enzyme
      free strategies: hybridization chain reaction (HCR) and enzyme-strand recycling
      reaction has been developed. The BPA aptamer can form hairpins structure by the
      partly self-complementary sequence. In the presence of BPA, the released BPA
      aptamer sequence can trigger the HCR between two hairpins to from a long nicked
      double-helix DNA. The tails of hairpins on the duplex DNA were closely enough to
      hybridize with molecular beacon (MB) on the gold nanoparticles (AuNPs) to
      circularly cleave the loop of MB, leading to a "turn-on" fluorescent signal. This
      method exhibited high sensitivity for BPA detection in a linear rang from 0.2 to
      1000 pM with 0.05 pM of limit of detection. Moreover, it was successfully used
      for BPA detection in real water samples. Importantly, this method was simple
      without complex enzymatic procedure and high cost, showing a promising future for
      on-site detection of BPA in practical application.

PMID- 29655421
TI  - A novel colorimetric aptasensor for ultrasensitive detection of cocaine based on
      the formation of three-way junction pockets on the surfaces of gold
      nanoparticles.
AB  - Herein, a novel colorimetric aptasensor was introduced for detection of cocaine
      based on the formation of three-way junction pockets on the surfaces of gold
      nanoparticles (AuNPs) and the catalytic activity of the surfaces of AuNPs.
      Simplicity and detection of cocaine in a short time (only 35 min) are some of the
      unique features of the proposed sensing strategy. In the presence of cocaine,
      triple-fragment aptamer (TFA) forms on the surfaces of AuNPs, leading to a
      significant decrease of the catalytic activity of AuNPs and the color of samples
      remains yellow. In the absence of target, TFA does not form on the surfaces of
      AuNPs and 4-Nitrophenol, as a colorimetric agent, has more access to the surfaces
      of AuNPs, resulting in the reduction of 4-Nitrophenol and the color of sample
      changes from yellow to colorless. The sensing strategy showed good specificity, a
      limit of detection (LOD) of 440 pM and a dynamic range over 2-100 nM. The sensing
      method was also successfully applied to detect cocaine in spiked human serum
      samples with recovery of 94.71-98.63%.

PMID- 29655422
TI  - Aptamer-based microcantilever-array biosensor for profenofos detection.
AB  - Profenofos, a highly poisonous organophosphorus pesticide, has been widely used
      in agricultural production. These pesticide residues have seriously influenced
      food security and threatened human health, and new methods with high sensitivity
      are greatly needed to detect profenofos. Here, we developed an aptamer-based
      microcantilever-array sensor operated in stress mode to detect profenofos, with
      advantages of being a label-free, highly sensitive, one-step immobilization
      method capable of quantitative and real-time detection. The microcantilevers were
      functionalized with a profenofos-specific aptamer (SS2-55), and then the specific
      binding of profenofos to aptamer induced a deflection of the microcantilever,
      which was monitored using an optical method in a real-time manner. The
      microcantilever deflection showed a positive relationship with profenofos
      concentration, and the detection limit was low to 1.3 ng mL-1 (3.5 nM) for
      profenofos, which was much lower than other aptamer-based detection methods. The
      selectivity of the sensor was verified with another organophosphorus pesticide.
      Additionally, we successfully detected profenofos dissolved in vegetable-soak
      solution. Our results showed that this aptamer-based microcantilever-array sensor
      is a convenient and label-free method for detecting profenofos in small amounts
      and has great potential for food-security applications.

PMID- 29655423
TI  - Aerosol sampler for analysis of fine and ultrafine aerosols.
AB  - A new aerosol sampler based on the original version of Aerosol Counterflow Two
      Jets Unit (ACTJU) is described. The ACTJU collector, connected with a water-based
      Condensation Growth Unit (CGU) placed upstream of the ACTJU, accomplished the
      quantitative collection of fine and ultrafine aerosol particles down to a few
      nanometers in diameter. Condensation of water vapor in the CGU enlarges nanometer
      sized particles to larger sizes in the supermicrometer range and the formed
      droplets are then collected into water in the ACTJU collector. The continuous
      collection of aerosols with the CGU-ACTJU sampler allows for the time-resolved
      measurement of changes in the concentration of particulate constituents. Coupling
      of the CGU-ACTJU sampler with on-line detection devices allows in-situ automated
      analysis of water-soluble aerosol components with high time resolution of 1 s
      (e.g., FIA detection for nitrite or nitrate) or 1 h (e.g., IC detection with
      preconcentration step for inorganic anions). Under the optimum conditions (the
      air flow rate of 10 L min-1 and water flow rate of 1.5 mL min-1), the limit of
      detection (IC including the preconcentration) for particulate fluoride, chloride,
      nitrite, nitrate, sulphate and phosphate is 2.53, 6.64, 24.2, 16.8, 0.12 and 5.03
      ng m-3, respectively. The apparatus is sufficiently robust for its application at
      routine monitoring of aerosol composition in real-time.

PMID- 29655424
TI  - Simultaneous elastase-, hyaluronidase- and collagenase-capillary electrophoresis
      based assay. Application to evaluate the bioactivity of the red alga Jania
      rubens.
AB  - There have been many efforts to search for affordable and efficient cosmetic
      ingredients from natural sources and to evaluate their bioactivities using eco
      responsible tools. Hyaluronidase, elastase and collagenase are responsible for
      the degradation of the main components of the extracellular matrix, namely the
      hyaluronic acid, elastin and collagen, respectively. The aim of this work was to
      develop a single capillary electrophoresis method to monitor simultaneously the
      activities of these three enzymes, without reactant immobilization or
      radioactivity use. The developed approach was used to evaluate the bioactivity of
      the red alga Jania rubens after microwave- or electrochemical-assisted
      extraction. For this purpose, the incubation time, the reactant concentrations,
      the separation buffer and the detection system were carefully chosen. CE with
      double detection system, LIF and HRMS connected in series, was used to ensure the
      simultaneous analysis of the substrates and products of the three enzymatic
      reactions. The optimized enzymatic conditions allowed the use of the same
      protocol to assess the 3 enzyme activities. These conditions consisted of 10 min
      pre-incubation of the enzyme (with alga extract) at 37  degrees C; 10 min
      incubation with the substrate at 37  degrees C and 10 min stop-time at 90 
      degrees C. 1.4 nL of each reaction mixture were co-injected into a 85 cm total
      length capillary using short-end injection. Ammonium acetate (50 mM, pH 9.0) was
      used for electrophoretic separation. All substrates and products were
      simultaneously detected in less than 10 min with good peak symmetry and
      efficiency, sufficient intra-day and inter-day repeatabilities (RSD < 4.5%; n =
      3) and excellent LOQ (<5 nM). The results obtained using this multiple CE-based
      enzymatic assay showed the significant effect of Jania rubens ethanolic extracts
      on elastase, hyaluronidase and the metalloproteinase MMP-1.

PMID- 29655425
TI  - Estimating the number of components and detecting outliers using Angle
      Distribution of Loading Subspaces (ADLS) in PCA analysis.
AB  - Principal Component Analysis (PCA) is widely used in analytical chemistry, to
      reduce the dimensionality of a multivariate data set in a few Principal
      Components (PCs) that summarize the predominant patterns in the data. An accurate
      estimate of the number of PCs is indispensable to provide meaningful
      interpretations and extract useful information. We show how existing estimates
      for the number of PCs may fall short for datasets with considerable coherence,
      noise or outlier presence. We present here how Angle Distribution of the Loading
      Subspaces (ADLS) can be used to estimate the number of PCs based on the
      variability of loading subspace across bootstrap resamples. Based on
      comprehensive comparisons with other well-known methods applied on simulated
      dataset, we show that ADLS (1) may quantify the stability of a PCA model with
      several numbers of PCs simultaneously; (2) better estimate the appropriate number
      of PCs when compared with the cross-validation and scree plot methods,
      specifically for coherent data, and (3) facilitate integrated outlier detection,
      which we introduce in this manuscript. We, in addition, demonstrate how the
      analysis of different types of real-life spectroscopic datasets may benefit from
      these advantages of ADLS.

PMID- 29655426
TI  - Highly efficient DNA extraction and purification from olive oil on a washable and
      reusable miniaturized device.
AB  - Sample preparation from complex matrixes with minute DNA content could highly
      benefit from the miniaturization of solid phase extraction (SPE) based devices
      due to an increased surface area-to-volume ratio. However, the adaptation of
      "bench-top" based protocols for DNA purification to miniaturized devices is not
      as straightforward as it might seem, and several issues need to be considered. A
      careful evaluation of DNA extraction and purification protocols needs to be
      performed, taking into account the complexity of such samples, and in order to
      facilitate the integration with the subsequent step, normally DNA amplification.
      In this work a washable and reusable miniaturized device for DNA purification
      based on microscale solid phase extraction (MUSPE), containing a commercial
      disposable silica membrane as the solid phase for DNA capture, was developed. The
      DNA purification protocol was firstly optimized by testing a set of different
      conditions, including buffer composition in all three steps of analysis and
      incubation during the elution step, with the objective of increasing the DNA
      yield and facilitating the integration in a miniaturized setting. This protocol
      was then tested with olive oil samples, including a pretreatment step also
      developed and optimized in this work. DNA analysis of olive oil samples is of
      high interest for the detection of fraudulent adulteration with oil from other
      seeds and for cultivar identification. The results were compared with the
      commercial NucleoSpin(r) Food kit regarding efficiency and purity of the DNA
      extract, by estimating the DNA yield and evaluating the absorbance ratios
      A260/280 and A260/230. The miniaturized DNA purification device showed better
      performance than the commercial kit tested, making this method a very promising
      sample preparation approach for olive oil and other samples with minute DNA
      content.

PMID- 29655427
TI  - Enhanced cleanup efficiency hydroxy functionalized-magnetic graphene oxide and
      its comparison with magnetic carboxyl-graphene for PRiME pass-through cleanup of
      strychnine and brucine in human plasma samples.
AB  - An enhanced cleanup efficiency hydroxy functionalized-magnetic graphene oxide (EH
      Mag-GO) fully covered porous nano-titania as coating has been designed and
      synthesized. It has been evaluated in PRiME (process, robustness, improvements,
      matrix effects, ease of use) pass-through cleanup procedure for human plasma
      prior to analysis of strychnine and brucine by liquid chromatography-tandem
      quadrupole mass spectrometry (LC-MS/MS). Comparing with the magnetic carboxyl
      graphene (Mag-CG), EH-Mag-GO is much more effective for the removal of matrix
      effect resulted from blood phospholipids. Under optimal conditions, the results
      show higher cleanup efficiency of EH-Mag-GO with recoveries in the range of 89.4%
      118%. The limits of quantification (LOQs) for strychnine and brucine are 0.088
      MUg/L and 0.092 MUg/L, respectively. Especially, the EH-Mag-GO is also evaluated
      for reuse (20 times) without much sacrifice of the cleanup efficiency. Validation
      results on linearity, specificity, accuracy and precision, as well as on the
      application to analysis of strychnine and brucine in six cases of suspected semen
      strychni poisoning demonstrate the applicability to clinical studies.

PMID- 29655428
TI  - Simultaneous determination of trace levels of multiclass fungicides in natural
      waters by solid - phase microextraction - gas chromatography-tandem mass
      spectrometry.
AB  - A solvent-free method based on solid-phase microextraction (SPME) followed by gas
      chromatography-tandem mass spectrometry (GC-MS/MS) has been developed for the
      simultaneous determination of eleven fungicides at trace levels in different
      types of waters. Several experimental SPME parameters such as temperature, fibre
      coating, and SPME mode, were optimized in order to obtain the highest extraction
      efficiency. Under the optimal conditions, 100  degrees C, polyacrilate fibre (PA)
      and direct-immersion mode, the method was validated showing good linearity,
      repeatability and reproducibility. Recovery studies were carried out in four
      different real water matrices and at three concentration levels (20, 200 and 2000
      ng L-1), with overall recovery values between 92 and 104% and relative standard
      deviations (RSD) about 10%. Limits of detection (LODs) at the low ng L-1 were
      obtained. The method demonstrated its suitability for the determination of
      fungicides in real water samples using external calibration for quantification
      purposes as well as for photodegradation studies at low concentration levels.

PMID- 29655429
TI  - Mass spectrometric recommendations for Quan/Qual analysis using liquid
      chromatography coupled to quadrupole time-of-flight mass spectrometry.
AB  - BACKGROUND: High-throughput simultaneous quantitative and qualitative (Quan/Qual)
      analysis is attractive to combine targeted with non-targeted analysis, e.g. in
      pharmacometabolomics and drug metabolism studies. This study aimed to investigate
      the possibilities and limitations of high-throughput Quan/Qual analysis by ultra
      high performance liquid chromatography (UHPLC) coupled with high-resolution mass
      spectrometry (HRMS), to develop a widely applicable Quan/Qual UHPLC-HRMS method
      and to provide recommendations for Quan/Qual method development. METHODS: A
      widely applicable 4.25-min UHPLC method for small-molecules was used to
      investigate and optimize mass spectrometric parameters of a Synapt G2S for
      Quan/Qual analysis. The method was applied on a rat metabolomics study
      investigating the effect of the fasting state and administration of a dosing
      vehicle on the rat plasma metabolic profile. RESULTS: Highly important parameters
      for high-throughput Quan/Qual analysis were the scan mode and scan rate. A
      negative correlation was found between the amount of qualitative information that
      a method can provide and its quantitative performance (accuracy, precision,
      sensitivity, linear dynamic range). The optimal balance was obtained using the
      MSE scan mode with a short scan time of 30 ms. This 4.25-min Quan/Qual analysis
      method enabled quantification with accuracy and precision values <= 20% at the
      lowest quality control (QC) level and <=15% at higher QC levels for 16 out of 19
      tested analytes. It provided both parent m/z values and fragmentation spectra for
      compound identification with limited loss of chromatographic resolution and it
      revealed biologically relevant metabolites in its application to the metabolomics
      study. CONCLUSION: Quan/Qual method development requires balancing between the
      amount of qualitative data, the quality of the quantitative data and the analysis
      time. Recommendations are provided for MS resolution, scan mode, scan rate,
      smoothing and peak integration in Quan/Qual method development and analysis.

PMID- 29655430
TI  - Use of dielectric barrier discharge ionization to minimize matrix effects and
      expand coverage in pesticide residue analysis by liquid chromatography-mass
      spectrometry.
AB  - Although electrospray ionization (ESI) remains the gold standard ionization
      source for LC-MS, it exhibits two main limitations: the occurrence of matrix
      effects and the limited ionization coverage towards nonpolar compounds.
      Dielectric barrier discharge ionization (DBDI) has gained attraction in recent
      years as a versatile ionization method in different applications and formats.
      Here, we report a thorough evaluation of DBDI as ionization interface for LC-MS,
      which reveals attractive advantages over ESI and atmospheric pressure chemical
      ionization (APCI) provided its singular ionization mechanism versatility. A suite
      of 80 pesticides across a wide range of physicochemical properties were selected
      and the results were compared with both ESI and APCI sources. Using a helium
      plasma operated in homogeneous regime with square-wave AC waveform and relatively
      low voltages (2.5 kV), not only DBDI was able to ionize compounds only amenable
      so far by GC-MS (eg. organochlorine species), but also offered a competitive
      performance in terms of sensitivity when contrasted with the commercial
      electrospray ionization source under equivalent conditions. Unlike ESI, DBDI
      mechanism occurs in the gas-phase, so the method is less affected by liquid-phase
      surface phenomena that yield ion suppression in ESI. Data collected in the
      positive ion mode revealed negligible matrix effect values (<10% suppression) for
      most of the studied compounds in different complex matrix extracts such as
      wastewater, orange or olive oil. This is also consistent with the absence of
      adduct formation whereas with ESI source, Na adduct formation is quite common
      with these species. In general, both sensitivity and average limits of
      quantitation for DBDI were similar to those obtained by ESI and better than APCI.
      Results showed that analyte coverage with DBDI is enhanced with respect to ESI
      and APCI sources being able to effectively analyze organochlorine compounds.

PMID- 29655431
TI  - Optical trapping-Raman spectroscopy (OT-RS) with embedded microscopy imaging for
      concurrent characterization and monitoring of physical and chemical properties of
      single particles.
AB  - The study of physical and chemical properties of a microscopic object, such as a
      single particle, is made possible using optical trapping (OT) technology combined
      with other measuring techniques. Here we show a universal optical trap combined
      with Raman spectroscopy (RS) and microscopy imaging for single-particle studies.
      The universal optical trap is constructed using two counter-propagating hollow
      beams and is able to stably levitate single particles of a wide range of
      properties, such as transparent or absorbing materials, organic (polymers,
      bioaerosols, etc.) or inorganic constituents (carbon, silica, glass, etc.), and
      spherical or irregularly shaped morphologies. Both physical and chemical
      properties and their temporal evolution of the trapped particle can be
      characterized simultaneously using the integrated OT-RS and imaging system. We
      created three sample cases to demonstrate the analytical merits of the system:
      (I) a single particle with no change, (II) partially degraded over the measuring
      period, and (III) one part from the fragmentized single particle. The particles'
      chemical compositions, crystalline states, etc. are inferred from their Raman
      spectra, while their physical properties (sizes, shapes, morphologies, etc.) are
      revealed by images. This integrated OT-RS system provides a new approach to
      concurrently characterize and monitor physical and chemical properties of single
      micrometer-sized objects optically trapped in air.

PMID- 29655432
TI  - The discrimination threshold: A selection criterion for analytical methods based
      on measurement uncertainty - Application to animal stress studies.
AB  - Many biological studies seek to confirm the effect of a treatment on the levels
      of chemical markers in biological tissues. This requires choosing the analytical
      method best able to detect the difference between basal levels and those found
      after treatment. We propose a new approach to calculate a criterion we call the
      'discrimination threshold' (DT), and we applied it to an analytical method that
      we developed to determine cortisol in cattle plasma to detect stress. DT is
      derived from the measurement uncertainty (MU), and combines the variabilities of
      both the analytical method and the marker. The uncertainty of the analytical
      method comes from the method validation study. The marker variability (here
      cortisol) is modeled from a literature review. The graphical representation of DT
      allows estimating the applicability of the method. Our analytical method is shown
      to perform well when the difference in blood cortisol exceeds 18 ng. mL-1.

PMID- 29655433
TI  - Spectrophotometric calibration procedures to enable calibration-free measurements
      of seawater calcium carbonate saturation states.
AB  - A simple protocol was developed to measure seawater calcium carbonate saturation
      states (Omegaspec) spectrophotometrically. Saturation states are typically
      derived from the separate measurement of two other carbon system parameters, with
      each requiring unique instrumentation and often complex measurement protocols.
      Using the new protocol, the only required equipment is a thermostatted laboratory
      spectrophotometer. For each seawater sample, spectrophotometric measurements of
      pH (visible absorbance) are made in paired optical cells, one with and one
      without added nitric acid. Ultraviolet absorbance is measured to determine the
      amount of added acid based on the direct proportionality between nitrate
      concentration and UV absorbance. Coupled measurements of pH and the alkalinity
      change that accompanies the nitric acid addition allow calculation of a seawater
      sample's original carbonate ion concentration and saturation state. These paired
      absorbance measurements yield Omegaspec (and other carbonate system parameters),
      with each sample requiring about 12 min processing time. Initially, an instrument
      specific nitrate molar absorptivity coefficient must be determined (due to small
      but significant discrepancies in instrumental wavelength calibrations), but
      thereafter no further calibration is needed. In this work, the 1sigma precision
      of replicate measurements of aragonite saturation state was found to be 0.020,
      and the average difference between Omegaspec and Omega calculated conventionally
      from measured total alkalinity and pH (Omegacalc) was -0.11% +/- 0.96% (a level
      of accuracy comparable to that obtained from spectrophotometric measurements of
      carbonate ion concentration). Over the entire range of experimental conditions,
      0.97 < Omega < 3.17 (n = 125), all measurements attained the Global Ocean
      Acidification Observing Network's "weather level" goal for accuracy and 90%
      attained the more stringent "climate level" goal. When Omegaspec was calculated
      from averages of duplicate samples (n = 56), the precision improved to 0.014 and
      the average difference between Omegaspec and Omegacalc improved to -0.11% +/-
      0.73%. Additionally, 97% of the duplicate-based Omegaspec measurements attained
      the "climate level" accuracy goal. These results indicate that the simple
      measurement protocol developed in this work should be widely applicable for
      monitoring fundamental seawater changes associated with ocean acidification.

PMID- 29655434
TI  - Improving quality of care in patients with Barrett's esophagus by measuring and
      improving neoplasia detection rates.

PMID- 29655435
TI  - Endoscopic removal of obstructing food bolus: Can a cap do the trick?

PMID- 29655436
TI  - Too loose to lose: an investigation into endoscopic anastomotic reduction to
      reestablish weight loss.

PMID- 29655437
TI  - Response.

PMID- 29655438
TI  - ERCP credentialing approaches in Australia and throughout the world.

PMID- 29655439
TI  - Response.

PMID- 29655440
TI  - Blood urea nitrogen increase is an expected finding in nonvariceal upper GI
      bleeding patients with underlying moderate or severe renal disease.

PMID- 29655441
TI  - Thoughts of the safety and efficacy of EUS-guided cyst ablation with the use of
      lauromacrogol.

PMID- 29655442
TI  - Response.

PMID- 29655443
TI  - Endoscopic submucosal dissection for early Barrett's esophagus neoplasia.

PMID- 29655444
TI  - Response.

PMID- 29655445
TI  - Risk management in port and maritime logistics.

PMID- 29655447
TI  - Ocular Myasthenia.
AB  - Ocular myasthenia is a form of myasthenia gravis in which weakness is restricted
      to the ocular muscles and may produce significant visual disability. Patients
      present with fluctuating ptosis, diplopia, or a combination of both. Examination
      may show any type of ocular motility deficit ranging from isolated muscle palsy
      to complete ophthalmoplegia. Cogan lid twitch, enhanced ptosis, peek sign, and
      saccadic fatigue are specific examination findings that support the clinical
      diagnosis of myasthenia gravis. Confirmation of the diagnosis is challenging with
      autoantibody serology, and repetitive nerve stimulation studies are often
      negative.

PMID- 29655446
TI  - Practical Anatomy of the Neuromuscular Junction in Health and Disease.
AB  - Neuromuscular junctions (NMJs) form between nerve terminals of spinal cord motor
      neurons and skeletal muscles, and perisynaptic Schwann cells and kranocytes cap
      NMJs. One muscle fiber has one NMJ, which is innervated by one motor nerve
      terminal. NMJs are excitatory synapses that use P/Q-type voltage-gated calcium
      channels to release the neurotransmitter acetylcholine. Acetylcholine receptors
      accumulate at the postsynaptic specialization called the end plate on the muscle
      fiber membrane, the sarcolemma. Proteins essential for the organization of end
      plates include agrin secreted from nerve terminals, Lrp4 and MuSK receptors for
      agrin, and Dok-7 and rapsyn cytosolic proteins in the muscle.

PMID- 29655448
TI  - Generalized Myasthenia Gravis: Classification, Clinical Presentation, Natural
      History, and Epidemiology.
AB  - Myasthenia gravis (MG) is a rare disease, but the most common disorder of the
      neuromuscular junction. It is the prototypic autoimmune disease most commonly
      caused by antibodies to the acetylcholine receptor (AChR) leading to
      characteristic fatigable weakness of the ocular, bulbar, respiratory, axial, and
      limb muscles. The majority of patients with MG first present with ocular
      symptoms. Most patients with MG will experience at least 1 exacerbation of
      symptoms throughout the course of their illness. This article will cover the
      epidemiology, clinical presentation, classification, and natural history of MG.

PMID- 29655449
TI  - Diagnosis of Myasthenia Gravis.
AB  - Myasthenia gravis (MG) diagnosis is primarily clinically based. By the end of the
      clinical evaluation, clinicians have a sense as to whether presenting symptoms
      and elicited signs are weakly or strongly supportive of MG. Diagnostic tests can
      reaffirm the clinicians' impression. Edrophonium testing is rarely used but
      helpful in cases of measurable ptosis. Decremental response on slow-frequency
      repetitive nerve stimulation has a modest diagnostic yield in ocular MG but is
      helpful in generalized MG cases. The most sensitive test is single-fiber
      electromyography. In this article, the authors review the diagnostic testing
      approach of practicing clinicians for suspected MG cases.

PMID- 29655450
TI  - Nature and Action of Antibodies in Myasthenia Gravis.
AB  - This article discusses antibodies associated with immune-mediated myasthenia
      gravis and the pathologic action of these antibodies at the neuromuscular
      junctions of skeletal muscle. To explain how these antibodies act, we consider
      the physiology of neuromuscular transmission with emphasis on 4 features: the
      structure of the neuromuscular junction; the roles of postsynaptic acetylcholine
      receptors and voltage-gated Na+ channels and in converting the chemical signal
      from the nerve terminal into a propagated action potential on the muscle fiber
      that triggers muscle contraction; the safety factor for neuromuscular
      transmission; and how the safety factor is reduced in different forms of
      autoimmune myasthenia gravis.

PMID- 29655452
TI  - Treatment of Myasthenia Gravis.
AB  - With specialized care, patients with myasthenia gravis can have very good
      outcomes. The mainstays of treatment are acetylcholinesterase inhibitors, and
      immunosuppressive and immunomodulatory therapies. There is good evidence
      thymectomy is beneficial in thymomatous and nonthymomatous disease. Nearly all of
      the drugs used for MG are considered "off-label." The 2 exceptions are
      acetylcholinesterase inhibitors and complement inhibition with eculizumab, which
      was recently approved by the US Food and Drug Administration for myasthenia
      gravis. This article reviews the evidence base and provides a framework for the
      treatment of myasthenia gravis, highlighting recent additions to the literature.

PMID- 29655453
TI  - Measuring Clinical Treatment Response in Myasthenia Gravis.
AB  - In this article we provide an overview of health-related outcome measurement-to
      better understand what different outcomes used in myasthenia actually measure-and
      to provide some guidance when choosing measures based on the clinical context and
      question. In myasthenia, the most commonly used outcome measures are aimed at
      assessing the signs and symptoms. In this review, we provide a summary of the
      most commonly used outcome measures. We discuss instruments that gauge disease
      overall health impact, such as on disability and quality of life. Finally, we
      discuss other relevant outcomes such as steroid-sparing effects and the role of
      surrogate markers.

PMID- 29655454
TI  - An Update: Myasthenia Gravis and Pregnancy.
AB  - Myasthenia gravis presents a risk factor for pregnancy and delivery, and can
      affect the newborn. In return, pregnancy can affect the course of myasthenia and
      worsen the disease during pregnancy requiring treatment modifications. Treatment
      optimization and drug safety should be addressed before conception. Delivery is
      complicated by prolonged labor. Newborns can develop neonatal myasthenia gravis,
      a treatable and transient disease. Patients should not be discouraged to become
      pregnant, but provided with supportive counseling, planning, and monitoring in a
      multidisciplinary team involving obstetrician, anesthesiologist, pediatrician,
      and neurologist. Pregnancy outcome is favorable in women who receive treatment
      and expert care.

PMID- 29655455
TI  - Congenital Myasthenic Syndromes.
AB  - The congenital myasthenic syndromes (CMS) are a group of rare genetic conditions
      characterized by abnormal neuromuscular transmission. Typically, these conditions
      have been the result of a dysfunctional protein that is present in the
      presynaptic terminal, the synaptic cleft, or the postsynaptic terminal. Many of
      these syndromes present within the first few years of life with fluctuating and
      fatiguable weakness in a distribution similar to myasthenia gravis, although a
      limb-girdle distribution and late onset are also seen in certain specific types
      of CMS. Electrodiagnostic testing with repetitive nerve stimulation may be
      helpful in some forms of CMS.

PMID- 29655456
TI  - Lambert-Eaton Myasthenic Syndrome.
AB  - Lambert-Eaton myasthenic syndrome is a paraneoplastic or primary autoimmune
      neuromuscular junction disorder characterized by proximal weakness, autonomic
      dysfunction and ariflexia. The characteristic symptoms are thought to be caused
      by antibodies generated against the P/Q-type voltage-gated calcium channels
      present on presynaptic nerve terminals and by diminished release of
      acetylcholine. More than half of Lambert-Eaton myasthenic syndrome cases are
      associated with small cell lung carcinoma. Diagnosis is confirmed by serologic
      testing and electrophysiologic studies. 3,4-diaminopyridine is effective
      symptomatic treatment of LEMS.

PMID- 29655451
TI  - Muscle-Specific Tyrosine Kinase and Myasthenia Gravis Owing to Other Antibodies.
AB  - Around 20% of patients with myasthenia gravis are acetylcholine receptor antibody
      negative; muscle-specific tyrosine kinase antibodies (MuSK) were identified as
      the cause of myasthenia gravis in 30% to 40% of these cases. Anti MuSK myasthenia
      gravis is associated with specific clinical phenotypes. One is a bulbar form with
      fewer ocular symptoms. Others show an isolated head drop or symptoms
      indistinguishable from acetylcholine receptor-positive myasthenia gravis. These
      patients usually respond well to immunosuppressive therapy, but not as well to
      cholinesterase inhibitors. Other antibodies associated with myasthenia gravis,
      including low-density lipoprotein receptor-related protein 4, are discussed.

PMID- 29655457
TI  - Fifty Key Publications on Myasthenia Gravis and Related Disorders.

PMID- 29655458
TI  - Standardization of BNP and NT-proBNP Immunoassays in Light of the Diverse and
      Complex Nature of Circulating BNP-Related Peptides.
AB  - Brain natriuretic peptide (BNP) and the N-terminal fragment of the BNP precursor
      (NT-proBNP) are widely used as heart failure (HF) biomarkers. Since the discovery
      of BNP in 1988, much effort has been allocated to the precise detection of BNP
      and NT-proBNP levels for reliable HF diagnostics. As a result, measurements of
      these biomarkers are globally accepted and used in clinical practice for the
      diagnosis of acute and chronic HF, risk stratification, and monitoring response
      to therapy. Several immunoassays specific for BNP and NT-proBNP are currently
      commercially available. Recent comparative studies show that there are marked
      differences between different BNP and NT-proBNP assays and platforms, and the
      results of measurements are not comparable enough. The lack of equivalence
      between the assays complicates the interpretation of the results and renders the
      cut-off points for diagnostic decisions to be method dependent. Presently, there
      is no agreement on what kind of BNP or NT-proBNP standard should be used for
      calibration, and a certified reference material as well as reference measurement
      procedures are lacking. The aim of this chapter is to summarize the available
      data on the complex nature of BNP-related peptides, specificity for existing BNP
      and NT-proBNP immunoassays, and to discuss potential approaches for
      standardization of BNP and NT-proBNP measurements.

PMID- 29655459
TI  - Adiponectin and Its Isoforms in Pathophysiology.
AB  - Adiponectin circulates in blood in multiple isoforms. High molecular weight (HMW)
      adiponectin is thought to be most biologically active and promotes glucose
      uptake, insulin sensitivity, and fatty acid oxidation. In obesity, adiponectin
      isoform formation is disrupted, leading to an inverse association between
      metabolic disease and HMW and total adiponectin. Adiponectin isoforms also
      function as acute-phase reactants influencing inflammation in acute and chronic
      disease. Interestingly, adiponectin and mortality have a U-shaped association.
      Unfortunately, data concerning adiponectin and its pathophysiologic function
      conflict. This is predominantly due to difficulties in adequate measurement of
      adiponectin isoforms and lack of a gold standard. In this review we provide a
      general overview of the formation and function of adiponectin and its isoforms
      under physiologic conditions. We highlight the ways adiponectin isoform formation
      is disrupted in obesity and its ensuing pathologic conditions. Furthermore, we
      will elaborate on the role of adiponectin isoforms as inflammatory proteins with
      respect to cardiac and kidney disease and discuss the association of adiponectin
      with mortality. Finally, we will provide a historical perspective on the
      measurement of adiponectin isoforms, current limitations, and future challenges.

PMID- 29655460
TI  - Uncertainty in Measurement: Procedures for Determining Uncertainty With
      Application to Clinical Laboratory Calculations.
AB  - In Part II of this review we consider the very common case of multiple inputs to
      a measurement process. We derive, using only elementary steps and the basic
      mathematics covered in Part I, the formula for the propagation of uncertainties
      from the inputs to the output. The Gaussian density distribution is briefly
      explained, since an understanding of this distribution is needed for the
      determination of so-called expanded uncertainties at the end of a measurement
      process. The propagation formula in general involves correlations among the
      inputs, although in many cases these correlations can be considered negligible.
      Correlations, however, need to be taken into account in related matters such as
      line-fitting and have particular relevance to method comparisons. These topics
      are addressed briefly. We next discuss the important question of bias and its
      incorporation into the expression of uncertainty. We present, finally, six real
      world cases in clinical chemistry where uncertainty in the estimated value of the
      measurand is calculated using the propagation formula.

PMID- 29655461
TI  - Metabolomics and Lipidomics of Ischemic Stroke.
AB  - Ischemic stroke is a sudden loss of brain function due to the reduction of blood
      flow. Brain tissues cease to function with subsequent activation of the ischemic
      cascade. Metabolomics and lipidomics are modern disciplines that characterize the
      metabolites and lipid components of a biological system, respectively. Because
      the pathogenesis of ischemic stroke is heterogeneous and multifactorial, it is
      crucial to establish comprehensive metabolomic and lipidomic approaches to
      elucidate these alterations in this disease. Fortunately, metabolomic and
      lipidomic studies have the distinct advantages of identifying tissue/mechanism
      specific biomarkers, predicting treatment and clinical outcome, and improving our
      understanding of the pathophysiologic basis of disease states. Therefore, recent
      applications of these analytical approaches in the early diagnosis of ischemic
      stroke were discussed. In addition, the emerging roles of metabolomics and
      lipidomics on ischemic stroke were summarized, in order to gain new insights into
      the mechanisms underlying ischemic stroke and in the search for novel metabolite
      biomarkers and their related pathways.

PMID- 29655462
TI  - Obesity, Thrombotic Risk, and Inflammation in Cancer.
AB  - : Neoplasms exhibits a high incidence and mortality rates due to their complex
      and commonly overlapping clinical, biochemical, and morphologic profiles
      influenced by acquired or inherited molecular abnormalities, cell of origin, and
      level of differentiation. Obesity appears related to ~20% of cancers including
      endometrial, esophageal, colorectal, postmenopausal breast, prostate, and renal.
      Several factors other than obesity, i.e., insulin, insulin-like growth factor,
      sexual hormones, and adipokines may play a potential role in neoplasia. Cancer
      associated hypercoagulable and thrombotic states are influenced by abnormalities
      in the vascular wall and susceptibility to invasion, interference in blood flow
      and increase in circulating tissue factor and thrombin, activation of cell growth
      factors, the presence of a central catheter, chemotherapies, neoplasm type, and
      surgery. In cancer, thromboembolic complications are the second most frequent
      cause of death with pulmonary thromboembolism in ~50% of cases postmortem.
      Thrombosis worsens prognosis as demonstrated with a survival rate as low as 12%
      per year vs 36% in nonthrombic patients. Deep vein thrombosis is the most
      frequent thromboembolic complication in cancer. It is usually detected at
      diagnosis and within the first 3 months of chemotherapy. The underlining
      mechanisms of this association should be further studied to identify patients at
      higher risk and develop adequate prevention, diagnostic, and treatment measures.
      The D-dimer test can be successfully used to assess the fibrinolytic phase of
      coagulation and as such is routinely used in suspected cases of deep vein
      thrombosis and pulmonary thromboembolism. In addition, significant advances have
      been made in understanding the composition and functional capabilities of the gut
      microbiota in the inflammatory process, obesity, and its roles in cancer;
      however, the intricate balance that exists within the microbiota may not only
      affect the host directly, it can also disrupt the entire microbial community.
      CONCLUSIONS: Cancer is a prothrombotic and inflammatory state in which the
      activation of coagulation is related to tumor growth, angiogenesis, and
      metastasis. It is important to identify the relationship between body mass index
      with these processes and clarify their importance in cancer prognosis. Future
      research should answer the question if manipulation of resident microbial
      communities could potentially improve prognosis and treatment outcome.

PMID- 29655464
TI  - Preface.

PMID- 29655463
TI  - Proteomics for Biomarker Identification and Clinical Application in Kidney
      Disease.
AB  - Treatment effectiveness for kidney disease is limited by lack of accuracy,
      sensitivity, specificity of diagnostic, prognostic, and therapeutic biomarkers.
      The gold standard test renal biopsy along with serum creatinine and proteinuria
      is often necessary to establish a diagnosis, particularly in glomerular disease.
      Proteomics has become a powerful tool for novel biomarker discovery in kidney
      disease. Novel proteomics offer earlier and more accurate diagnosis of renal
      pathology than possible with traditional biomarkers such as serum creatinine and
      urine protein. In addition, proteomic biomarkers could also be useful to choose
      the most suitable therapeutic targets. This review focuses on the current status
      of proteomic biomarkers from animal models (5/6 nephrectomy, unilateral ureteral
      obstruction, and diabetic nephropathy) and human studies (chronic kidney disease,
      glomerular diseases, transplantation, dialysis, acute and drug-induced kidney
      injury) to assess relevant findings and clinical usefulness. Current issues and
      problems related to the discovery, validation, and clinical application of
      proteomic biomarkers are discussed. We also describe several proteomic strategies
      highlighting technologic advancements, specimen selection, data processing and
      analysis. This review might provide help in future proteomic studies to improve
      the diagnosis and management of kidney disease.

PMID- 29655465
TI  - Translating Pharmacokinetic and Pharmacodynamic Data into Practice.
AB  - Pharmacokinetic (PK) and pharmacodynamic (PD) publications provide scientific
      evidence for incorporation in evidence-based veterinary medicine, aiding the
      clinician in selecting doses and dosing intervals. PK and PD studies have
      reported wide variations within exotic species, due to physiologic differences in
      absorption, distribution, metabolism, and excretion. PK studies offer species
      specific data to help tailor doses and dosing routes to individual patients,
      minimize toxicity, and provide a cornerstone for PD studies to determine drug
      efficacy. This article reviews the application of PK parameters and the
      challenges in determining the PD activity of drugs, with a particular emphasis on
      exotic species.

PMID- 29655466
TI  - The Educated Guess: Determining Drug Doses in Exotic Animals Using Evidence-Based
      Medicine.
AB  - Lack of species-specific pharmacokinetic and pharmacodynamic data is a challenge
      for pharmaceutical and dose selection. If available, dose extrapolation can be
      accomplished via basic equations. If unavailable, several methods have been
      described. Linear scaling uses an established milligrams per kilograms dose based
      on weight. This does not allow for differences in species drug metabolism,
      sometimes resulting in toxicity. Allometric scaling correlates body weight and
      metabolic rate but fails for drugs with significant hepatic metabolism and cannot
      be extrapolated to avians or reptiles. Evidence-based veterinary medicine for
      dose design based on species similarity is discussed, considering physiologic
      differences between classes.

PMID- 29655467
TI  - Compounding and Extralabel Use of Drugs in Exotic Animal Medicine.
AB  - Extralabel drug use is the use of a Food and Drug Administration (FDA)-approved
      drug in a manner different from what is stipulated on the approved label.
      Compounding is the process of preparing a medication in a manner not indicated on
      the label to create a formulation specifically tailored to the needs of an
      individual patient. Extralabel drug use and compounding are vital aspects of safe
      and effective drug delivery to patients in exotic animal practice. There are few
      FDA-approved drugs for exotic animal species, and many approved drugs for other
      species are not available in suitable formulations for use in exotic animals.

PMID- 29655468
TI  - Overview of Drug Delivery Methods in Exotics, Including Their Anatomic and
      Physiologic Considerations.
AB  - Drug delivery to exotic animals may be extrapolated from domestic animals, but
      some physiologic and anatomic differences complicate treatment administration.
      Knowing these differences enables one to choose optimal routes for drug delivery.
      This review provides practitioners with a detailed review of the currently
      reported methods used for drug delivery of various medications in the most common
      exotic animal species. Exotic animal peculiarities that are relevant for drug
      administration are discussed in the text and outlined in tables and boxes to help
      the reader easily find targeted information.

PMID- 29655469
TI  - Low-Stress Medication Techniques in Birds and Small Mammals.
AB  - Low-stress medication principles and techniques are key aspects of optimal health
      care delivery for birds and small mammals. When paired with the medical details
      of patient management, by balancing medication techniques, the probability of
      clinical success on the highest ethical and welfare criteria can be greatly
      enhanced. This review addresses both the effects and the disadvantages of using
      forceful, coercive, and fear-evoking methods as well as the benefits, principles,
      and possible applications of low-stress medication in the veterinary setting.

PMID- 29655470
TI  - Techniques for Monitoring Drug Efficacy.
AB  - The efficacy of drugs can vary greatly between species and individuals.
      Establishing efficacious drug doses for a species requires integration of
      population pharmacokinetic and pharmacodynamic data into a dose-response curve.
      Unfortunately, these data sets are rarely available for exotic species. The use
      of alternative monitoring techniques is required to determine drug efficacy and
      safety. This article discusses methods to integrate efficacy monitoring into
      clinical practice, including the use of diagnostic testing and therapeutic drug
      monitoring.

PMID- 29655471
TI  - Group Treatment Strategies for Animals in a Zoologic Setting.
AB  - Providing care for groups of animals is a major part of practicing zoologic
      medicine. Herd health is key to the mindset of a zoo clinician no matter the
      species encountered. Group treatment of amphibians and birds is common, but it is
      uncommon in reptiles and most mammals. The main reason groups of mammals are
      treated is for gastrointestinal parasitism. In addition to the classic examples
      of group treatment involving chemotherapeutics, zoo clinicians also practice herd
      health by preventing disease from entering the collection. Thorough disease
      screening via preshipment examinations, quarantine, and a rigorous necropsy
      protocol are vital tools to maintain a healthy collection.

PMID- 29655472
TI  - Considerations for Treatment of Large Zoologic Collections: Fish.
AB  - Aquatic species live most or all their lives in water; therefore, the health of
      the environment is intimately connected to their health and medical care.
      Understanding and maintaining appropriate husbandry and nutrition for the housed
      aquarium species are essential to sustain health. Most diseases of fish are
      secondary opportunistic infections; prevention and early diagnosis are
      recommended. Treatments involve environmental and/or nutritional management
      first, followed by targeted pharmacologic treatment to control a specific
      pathogen. Pharmacokinetic research evaluating the effects and safety of
      medications in fish are greatly needed in the peer-reviewed literature.

PMID- 29655473
TI  - Therapeutic Contraindications in Exotic Pets.
AB  - The selection and dosing of medications for exotic pets are often challenging
      because most drugs are used in an extralabel manner without pharmacokinetic and
      pharmacodynamic studies. Doses are often extrapolated from common domestic
      animals and safety data are often lacking in exotic species. Just as the
      bioavailability and therapeutic levels are different for each species, what may
      be a safe and commonly used medication in one species can be deadly in another.
      Various drugs with documented contraindications in certain exotic pet species are
      outlined in this review and the pathophysiology, clinical signs, and treatment
      options are described when applicable.

PMID- 29655474
TI  - Prudent Use of Antimicrobials in Exotic Animal Medicine.
AB  - Reduction of antimicrobial use can result in reduction of resistance in commensal
      bacteria. In exotic animals, information on use of antimicrobials and resistance
      in commensals and pathogens is scarce. However, use of antimicrobials listed as
      critically important antimicrobials for human medicine seems high in exotic
      animals. Ideally, the selection of a therapy should be based on an accurate
      diagnosis and antimicrobial susceptibility testing. When prescribing
      antimicrobials based on empiricism, knowledge of the most common pathogens
      causing specific infections and the antimicrobial spectrum of antimicrobial
      agents is indispensable. Implementing antimicrobial stewardship promotes the
      prudent use of antimicrobials in exotic animals.

PMID- 29655475
TI  - Antifungal Therapy in Birds: Old Drugs in a New Jacket.
AB  - The use of antifungals in birds is characterized by interspecies and
      interindividual variability in the pharmacokinetics, affecting drug safety and
      efficacy. Oral antifungal drug absorption is a complex process affected by drug
      formulation characteristics, gastrointestinal anatomy, and physiology. New
      antifungal drug delivery systems can enhance drug stability, reduce off-target
      side effects, prolong residence time in the blood, and improve efficacy. Topical
      administration of antifungals through nebulization shows promising results.
      However, therapeutic output is highly influenced by drug formulation and type of
      nebulizer, indicating these factors should be taken into account when selecting
      this medication route.

PMID- 29655476
TI  - Avian Vaccination: Current Options and Strategies.
AB  - Researchers have generated an array of potential avian antiviral vaccines.
      However, vaccine and viral complexity, small profit margins, the cost of
      development and manufacturing, and the small population at risk relegate most
      avian vaccine use to commercial species. Some vaccines designed for use in
      nonavian species are used to prevent or ameliorate disease in exotic and
      companion birds. This article highlights newly developed vaccines that may be
      used in exotic and pet birds. Information pertinent to vaccine choice and
      strategy is provided, including disease lethality, species affected, and previous
      knowledge regarding vaccine safety and efficacy. Other avian species of concern
      are also included.

PMID- 29655477
TI  - Cardiovascular Drugs in Avian, Small Mammal, and Reptile Medicine.
AB  - Cardiovascular disease, including congestive heart failure, pericardial disease,
      and atherosclerosis, is becoming increasingly better recognized in companion
      birds, small mammals, and reptiles. A wide range of medications is available to
      treat these conditions, including diuretics, vasodilators, positive and negative
      inotropes, antiarrhythmic agents, and pentoxifylline. This review systematically
      discusses each of these drug classes and their potential applications in exotic
      species. Although treatment approaches remain largely empirical and extrapolated
      from small animal and human medicine, the management strategies presented here
      have the potential to both maintain quality of life and extend survival time for
      the exotic cardiac patient.

PMID- 29655478
TI  - Gonadotrophin-Releasing Hormone Agonists and Other Contraceptive Medications in
      Exotic Companion Animals.
AB  - The use of a gonadotrophin-releasing hormone agonist slow-release implant (GnRH A
      SRI) has become increasingly popular as an alternative for surgical contraception
      in many species. Although these implants have proven to be very effective in some
      species (eg, ferrets, rats, chicken, psittacines, and iguanas), they have been
      found less effective in other species (eg, male guinea pigs and rabbits, veiled
      chameleons, slider turtles, and leopard geckos). This review provides an overview
      of the available literature on the effects of GnRH A-SRIs in companion exotic
      animals.

PMID- 29655479
TI  - Update on Cancer Treatment in Exotics.
AB  - Treatment options for animals with cancer are rapidly expanding, including in
      exotic animal medicine. Limited information is available about treatment effects
      in exotic pet species beyond individual case reports. Most cancer treatment
      protocols in exotic animals are extrapolated from those described in humans,
      dogs, and cats. This review provides an update on cancer treatment in exotic
      animal species. The Exotic Species Cancer Research Alliance accumulates clinical
      cases in a central location with standardized clinical information, with
      resources to help clinicians find and enter their cases for the collective good
      of exotic clinicians and their patients.

PMID- 29655481
TI  - Therapeutics.

PMID- 29655480
TI  - Nontraditional Therapies (Traditional Chinese Veterinary Medicine and
      Chiropractic) in Exotic Animals.
AB  - The nontraditional therapies of Traditional Chinese Veterinary Medicine and
      chiropractic care are adjunct treatments that can be used in conjunction with
      more conventional therapies to treat a variety of medical conditions.
      Nontraditional therapies do not need to be alternatives to Western medicine but,
      instead, can be used simultaneously. Exotic animal practitioners should have a
      basic understanding of nontraditional therapies for both client education and
      patient referral because they can enhance the quality of life, longevity, and
      positive outcomes for various cases across multiple taxa.

PMID- 29655482
TI  - Photoallergic Contact Dermatitis to Sunscreens Containing Oxybenzone in La Plata,
      Argentina.
AB  - BACKGROUND: Photoallergic contact dermatitis (PACD) to oxybenzone was reported
      for the first time in 1980. Oxybenzone is the most common photoallergen in the
      United States and Canada and the fourth most common .in Europe. There are no
      studies or data on the prevalence of oxybenzone PACD in Argentina. OBJECTIVE: To
      determine the proportion of photosensitive patients with PACD to oxybenzone.
      METHODS: We conducted a descriptive cross-sectional study of 35 patients with
      photosensitivity reactions confirmed by photopatch testing at the Research Center
      of Hospital Publico San Martin in La Plata, Argentina, in 2015 and 2016. RESULTS:
      PACD was identified in 6 patients (17.14%). Five of these (14.28%) had at least
      one positive reaction to oxybenzone in the photopatch test; 4 had a reaction at
      irradiated sites only (5 J/cm2 UVA) and one had a reaction at both irradiated and
      nonirradiated sites. CONCLUSIONS: PACD to sunscreens containing oxybenzone is
      common and is probably underdiagnosed due to a lack of confirmation by photopatch
      tests or other diagnostic tools. Sensitization rates vary according to region and
      are influenced by sunscreen ingredients and variations in the use of sunscreen
      products, cosmetics, and topical drugs.

PMID- 29655483
TI  - Chromatin Fiber Folding Directed by Cooperative Histone Tail Acetylation and
      Linker Histone Binding.
AB  - In eukaryotic chromatin, islands of histone tail acetylation are found near
      transcription start sites and enhancers, whereas linker histones (LHs) are
      localized in intergenic regions with wild-type (WT) histone tails. However, the
      structural mechanisms by which acetylation, in combination with LH binding,
      modulates chromatin compaction and hence transcription regulation are unknown. To
      explore the folding propensity by which these features may govern gene
      expression, we analyze 20 kb fibers that contain regularly spaced acetylation
      islands of two sizes (2 or 5 kb) with various LH levels by mesoscale modeling.
      Specifically, we investigate the effect of acetylating each histone tail (H3, H4,
      H2A, and H2B) individually, in combination (H3 and H4, or all tails), and adding
      LH to WT regions. We find that fibers with acetylated H4 tails lose local
      contacts (<1 kb) and fibers with all tails acetylated have decreased long-range
      contacts in those regions. Tail interaction plots show that this opening of the
      fiber is driven by the loss of tail-tail interactions in favor of tail-parent
      core interactions and/or increase in free tails. When adding LH to WT regions,
      the fibers undergo hierarchical looping, enriching long-range contacts between WT
      and acetylated domains. For reference, adding LH to the entire fiber results in
      local condensation and loss of overall long-range contacts. These findings
      highlight the cooperation between histone tail acetylation and regulatory
      proteins like LH in directing folding and structural heterogeneity of chromatin
      fibers. The results advance our understanding of chromatin contact domains, which
      represent a pivotal part of the cell cycle, diseased states, and differentiation
      states in eukaryotic cells.

PMID- 29655485
TI  - [Cost of clotting factors in hospitalization].
AB  - OBJECTIVES: Hemophilia is a rare genetic disease, characterized by uncontrolled
      bleeding. Injections of clotting factor are the principal are the principal
      treatment. This drug is very expensive. The objectives of this study are to
      determine the cost of clotting factor for in patients and the factor impacting
      this cost. METHODS: A retrospective study was carried on hemophiliac in patients
      between 1 January 2014 and 31 December 2015 in Cochin hospital and having
      received at least an injection of clotting factor during their hospitalization. A
      collection of clinical data and treatments received during the hospitalization
      was realized for every patient. RESULTS: Fifty-one patients were included in the
      study with a total of 68 hospitalizations. The median cost of clotting factors by
      hospitalization was 16,908?. The median part of clotting factors on the total
      cost of the hospitalization was 68.2%. The cost of factors by stay was higher for
      the severe haemophiliacs (P=0.015) and for the major surgeries (P<0.0001). The
      daily median cost of clotting factors was 3124?. This cost was higher at the
      haemophiliacs B (P=0.0112), the severe haemophiliacs (P<0.0001) and the
      haemophiliacs with inhibitor (P=0.0053). CONCLUSIONS: Clotting factors represent
      the most part of the cost of hospitalization of a haemophiliac. Their cost in
      hospitalization varies according to many factors. It may evolve with the arrival
      of long-acting clotting factors.

PMID- 29655484
TI  - Oral pentobarbital suspension for children sedation during MR imaging.
AB  - OBJECTIVES: The efficacy and safety of an oral pentobarbital suspension for
      sedation during pediatric MR imaging were assessed. METHODS: Data were recorded
      from October 2016 to January 2017. The exact dose of oral pentobarbital
      suspension was given for each child with an oral syringe. Parameters recorded
      included the patient's age and weight, the time required to sedate, the duration
      of sedation, the time required to discharge, and quality of MR imaging. The
      adverse effects were recorded. RESULTS: Oral pentobarbital suspension was
      administered to 81 children aged from 8 months to 8 years at a dose of 5mg/kg of
      body weight. The mean time required to sedate was 30+/-21min, a mean time of
      sedation of 47+/-23min, and a mean time to discharge of 77+/-32min. Sedation
      occurred a satisfied quality of MR imaging in 67% of patients. The failure of
      examination was essentially due to bad taste of the drug suspension. The overall
      success rate of sedation in patients less than 12 months was 100%. For ages 1 to
      3 years, the success rate decreased to 76% and for ages 4 to 8 years, it
      decreased to 42%. CONCLUSIONS: Oral pentobarbital suspension used in MR imaging
      demonstrated its high rate of successful sedation in infants less than 12 months
      with no adverse effects during the study period.

PMID- 29655486
TI  - Comprehensive simulation on morphological and mechanical properties of trigger
      finger - A cadaveric model.
AB  - Trigger finger has long been a common disorder in hand orthopedics. To clarify
      the unknown causative factors regarding the disease, numerous experiments were
      done on human cadavers, including tendon forces, tendon moment arm, mechanical
      properties of the pulley, gliding resistance, etc. However, most of these studies
      were conducted on normal fingers. As the etiology of trigger finger is still
      controversial on whether it is an outcome of tendon nodule or pulley scarring, in
      this study, a trigger finger model was built combining both the nodule created by
      silicone gel injection and pulley constriction by external compression.
      Indentation and gliding resistance tests were performed on cadaveric specimens to
      verify the model. Results showed that after silicone gel injection into the
      tendon, a significant increase in thickness was found. In addition, no
      significant difference was found in the toe region compressive modulus of the
      tendon after injection. Moreover, maximum, drop of gliding resistance and work of
      extension were all found to be significantly larger as the severity of triggering
      increased. Our results indicated we have developed a feasible cadaver model
      simulating trigger finger nodule which could be utilized for further experiments
      to elucidate other causative factors and biomechanical features of trigger finger
      in the future.

PMID- 29655487
TI  - Frequency of Aquaporin-4 Immunoglobulin G in Longitudinally Extensive Transverse
      Myelitis With Antiphospholipid Antibodies.
AB  - Antiphospholipid (aPL) antibodies have historically been postulated to cause a
      poorly understood inflammatory myelitis. Neuromyelitis optica spectrum disorder
      (NMOSD) causes an inflammatory longitudinally extensive transverse myelitis
      (LETM). In 2004, aquaporin-4 immunoglobulin G (AQP4-IgG) was first reported as a
      highly specific (>99%) serum diagnostic biomarker of NMOSD, distinguishing it
      from other disorders (eg, multiple sclerosis). We sought to assess the frequency
      of AQP4-IgG (and thus NMOSD diagnosis) in LETM with aPL antibodies. We searched
      Mayo Clinic records (from January 1, 1996, through December 31, 2014) for
      patients with (1) LETM and (2) aPL or beta2-glycoprotein I antibodies and (3) a
      serum sample available. AQP4-IgG was evaluated in the 24 included patients and in
      20 controls with aPL antibodies but without myelitis. Seropositivity for AQP4-IgG
      was confirmed in 11 of 24 patients with LETM (46%), confirming an AQP4-IgG
      seropositive NMOSD diagnosis rather than aPL-associated LETM. Six of 11 AQP4-IgG
      seropositive patients (54%) were initially diagnosed as having aPL/lupus
      associated myelitis. Recurrent LETM was exclusive to AQP4-IgG-seropositive
      patients (P=.003). Alternative diagnoses assigned to the remaining 13 AQP4-IgG
      seronegative patients included idiopathic transverse myelitis (n=5), seronegative
      NMOSD (n=2), spinal cord infarct attributed to aPL antibodies (n=2), spinal cord
      sarcoidosis (n=1), varicella-zoster virus myelitis (n=1), postinfectious myelitis
      (n=1), and multiple sclerosis (n=1). All 20 controls were seronegative for AQP4
      IgG. Clotting disorders occurred in 36% of patients (4 of 11) with LETM with both
      aPL antibodies and AQP4-IgG. AQP4-IgG should be tested in all patients with LETM
      and aPL antibodies because AQP4-IgG-seropositive NMOSD accounts for almost half
      of all cases. Clotting disorders are common in patients with LETM with dual
      positivity for AQP4-IgG and aPL antibodies.

PMID- 29655488
TI  - Discriminability of numerosity-evoked fMRI activity patterns in human intra
      parietal cortex reflects behavioral numerical acuity.
AB  - Areas of the primate intraparietal cortex have been identified as an important
      substrate of numerical cognition. In human fMRI studies, activity patterns in
      these and other areas have allowed researchers to read out the numerosity a
      subject is viewing, but the relation of such decodable information with
      behavioral numerical proficiency remains unknown. Here, we estimated the
      precision of behavioral numerosity discrimination (internal Weber fraction) in
      twelve adult subjects based on psychophysical testing in a delayed numerosity
      comparison task outside the scanner. FMRI data were then recorded during a
      similar task, to obtain the accuracy with which the same sample numerosities
      could be read out from evoked brain activity patterns, as a measure of the
      precision of the neuronal representation. Sample numerosities were decodable in
      both early visual and intra-parietal cortex with approximately equal accuracy on
      average. In parietal cortex, smaller numerosities were better discriminated than
      larger numerosities of the same ratio, paralleling smaller behavioral Weber
      fractions for smaller numerosities. Furthermore, in parietal but not early visual
      cortex, fMRI decoding performance was correlated with behavioral number
      discrimination acuity across subjects (subjects with a more precise behavioral
      Weber fraction measured prior to scanning showed greater discriminability of fMRI
      activity patterns in intraparietal cortex, and more specifically, the right LIP
      region). These results suggest a crucial role for intra-parietal cortex in
      supporting a numerical representation which is explicitly read out for numerical
      decisions and behavior.

PMID- 29655489
TI  - The Cochleural Alternating Acoustic Beam Therapy (CAABT): A pre-clinical trial.
AB  - PURPOSE: We intend to assess the effectiveness of a novel tinnitus treatment
      therapy, the Cochleural Alternating Acoustic Beam Therapy (CAABT) using the
      psychoacoustic measures, the questionnaires and rs-fMRI. MATERIALS AND METHODS:
      In this study, we enrolled 11 older than 18 years old Chinese patients with
      normal hearing who had unilateral, chronic (longer than 6 months), sensorineural
      tinnitus, of frequencies between 125-8000 Hz, and an average loudness of 31 dB.
      The patients underwent the treatment with the CAABT method for 12 weeks and the
      outcomes were evaluated with tinnitus questionnaire scores, a set of
      psychoacoustic measures, and rs-fMRI testing before treatment and at 3 months.
      This was an earlier study of the controlled randomized clinical trial which was
      registered with ClinicalTrials.gov, number NCT02774122. RESULTS: Almost all the
      patients reported reduced tinnitus annoyance after the three-month treatment. The
      THI and VAS scores showed decreased tinnitus severity. The rs-fMRI results
      indicated that the right middle frontal gyrus and the right superior temporal
      gyrus displayed noticeable decreases of the ReHo values for the subjects between
      the before and after treatment, supporting the clinical evidence of significant
      tinnitus reduction. CONCLUSION: The therapy seemed effective in patients of
      varying severities, and no side effects were observed in this trial. The CAABT
      can be an alternative for those who are suitable for sound therapy once a large
      scale of and better controlled clinical studies have validated the findings of
      this experiment.

PMID- 29655490
TI  - Effect of changing postoperative pain management on bleeding rates in
      tonsillectomy patients.
AB  - PURPOSE: To review rates of post-tonsillectomy hemorrhage (PTH) at a quaternary
      medical center, including the impact of narcotic versus nonsteroidal anti
      inflammatory drug (NSAID) postoperative pain management. MATERIALS AND METHODS: A
      retrospective review was performed of tonsillectomies conducted at a single
      institution between 1/1/2013 and 1/1/2017. The rates of PTH and subsequent
      intervention were calculated. These were categorized into patients having surgery
      pre- and post-July 1, 2015, the former group receiving narcotics and the latter
      ibuprofen with acetaminophen. RESULTS: Of 1351 total tonsillectomies, 3.04% had
      PTH requiring return to the hospital. 0.74% required no further surgical
      intervention, whereas 2.30% required secondary surgical control. The bleed rate
      prior to July 2015 was 3.15%, with 1.05% non-surgical bleeds and 2.10% requiring
      surgery. Post-July 2015, the bleed rate was 2.92%, with 0.44% non-surgical bleeds
      and 2.49% requiring surgery. There were no statistically significant differences
      between the two groups with respect to overall, non-surgical, and surgical
      hemorrhage rates (p > 0.05). Of the total bleeds, the need for secondary surgery
      in the narcotic group was 66.7% and 85% in the NSAID group (p = 0.18). During the
      study period, 36 patients with PTH had their initial tonsillectomy performed at
      outside institutions; 53% required surgical intervention. CONCLUSIONS: Secondary
      hemorrhage remains a significant cause of morbidity in post-tonsillectomy
      patients, often requiring surgical intervention. This review found no increased
      bleeding risk associated with use of ibuprofen and acetaminophen as opposed to
      narcotic pain relief. LEVEL OF EVIDENCE: III.

PMID- 29655491
TI  - Recertification is comming. Afraid? Not al all.

PMID- 29655492
TI  - Isolated Acute Appendicitis Caused by Aspergillus in a Patient Who Underwent Lung
      Transplantation: A Case Report.
AB  - Invasive aspergillosis is an important cause of morbidity and mortality in
      patients who have undergone lung transplantation. Aspergillus infections usually
      involve the respiratory tract, with vascular invasion and subsequent
      dissemination. However, acute appendicitis associated with localized
      aspergillosis is rare, especially among patients who have undergone prophylaxis
      with voriconazole. We present a case of primary Aspergillus appendicitis
      diagnosed by histologic examination in a patient who underwent lung
      transplantation. A 51-year-old woman with dermatomyositis underwent lung
      transplantation for acute interstitial pneumonitis. According to our
      institution's protocol, the patient was treated with immunosuppressive therapy
      and prophylaxis with voriconazole, ganciclovir, and trimethoprim sulfamethoxazole
      during the post-transplantation period. Twenty-eight days after transplantation,
      the patient developed mild abdominal pain and paralytic ileus. There was no
      apparent infection sign. Abdominal computerized tomography indicated a wall
      defect of the appendix with multifocal fluid collection, mesenteric leave
      thickening, and pneumoperitoneum. These findings were consistent with perforated
      appendicitis, and the patient underwent an appendectomy. The histopathology
      examination of the resected appendix showed inflammation and abscess. Periodic
      acid-Schiff-positive and Grocott-Gomori methenamine silver-positive fungal hyphae
      with acute-angle branching were observed, demonstrating muscular invasion. A
      galactomannan antigen test obtained on the same day had negative results. The
      trough level of voriconazole was well maintained and was subsequently adjusted
      through monitoring of circulating drug concentration. Simultaneously, other
      potential sites of disseminated Aspergillus were considered and examined, but no
      other site of systemic Aspergillus infection was detected. Voriconazole treatment
      was maintained for 3 months, and no aspergillosis relapse or other invasive
      fungal infections were observed.

PMID- 29655493
TI  - Hepatic inflammatory pseudotumor related with IgG4.

PMID- 29655494
TI  - Translumbar and transhepatic hemodialysis catheters: A viable option.

PMID- 29655495
TI  - Insecticide-resistant malaria vectors must be tackled.

PMID- 29655497
TI  - The AAHKS Clinical Research Award: Intraosseous Regional Prophylaxis Provides
      Higher Tissue Concentrations in High BMI Patients in Total Knee Arthroplasty: A
      Randomized Trial.
AB  - BACKGROUND: Obesity is an established risk factor for periprosthetic joint
      infections after total knee arthroplasty (TKA). In obese patients, a larger dose
      of prophylactic vancomycin based on actual body weight is required to reach
      therapeutic concentrations. It is unclear how tissue concentrations are affected
      when intraosseous regional administration (IORA) is used in this population. This
      study compared tissue concentrations of low-dose vancomycin via IORA vs actual
      body weight-adjusted systemic intravenous (IV) dose in primary TKA. METHODS:
      Twenty-two patients with a body mass index (BMI) >35 undergoing TKA were
      randomized into 2 groups. The IV group received 15 mg/kg (maximum of 2 g) of
      systemic IV vancomycin and the IORA group received 500 mg vancomycin into the
      tibia. Subcutaneous fat and bone samples were taken at regular intervals. Tissue
      antibiotic concentrations were measured using liquid chromatography coupled with
      tandem mass spectrometry. A blood sample was taken 1 to 2 hours after tourniquet
      deflation to measure systemic concentration. RESULTS: The mean BMI was 41.1 in
      the IORA group and 40.1 in the IV systemic group. The overall mean tissue
      concentration in subcutaneous fat was 39.3 MUg/g in the IORA group and 4.4 MUg/g
      in the IV systemic group (P < .01). Mean tissue concentrations in bones were 34.4
      MUg/g in the IORA group and 6.1 MUg/g in the IV systemic group (P < .01).
      CONCLUSION: Low-dose IORA was effective in the high-BMI population group,
      providing tissue concentrations of vancomycin 5-9 times higher than systemic
      administration. IORA optimizes timing of vancomycin administration and provides
      high tissue antibiotic concentrations during TKA in this high-risk patient group.

PMID- 29655498
TI  - Dietary Management of Hyperphosphatemia.

PMID- 29655496
TI  - Effectiveness of a long-lasting piperonyl butoxide-treated insecticidal net and
      indoor residual spray interventions, separately and together, against malaria
      transmitted by pyrethroid-resistant mosquitoes: a cluster, randomised controlled,
      two-by-two factorial design trial.
AB  - BACKGROUND: Progress in malaria control is under threat by wide-scale insecticide
      resistance in malaria vectors. Two recent vector control products have been
      developed: a long-lasting insecticidal net that incorporates a synergist
      piperonyl butoxide (PBO) and a long-lasting indoor residual spraying formulation
      of the insecticide pirimiphos-methyl. We evaluated the effectiveness of PBO long
      lasting insecticidal nets versus standard long-lasting insecticidal nets as
      single interventions and in combination with the indoor residual spraying of
      pirimiphos-methyl. METHODS: We did a four-group cluster randomised controlled
      trial using a two-by-two factorial design of 48 clusters derived from 40 villages
      in Muleba (Kagera, Tanzania). We randomly assigned these clusters using
      restricted randomisation to four groups: standard long-lasting insecticidal nets,
      PBO long-lasting insecticidal nets, standard long-lasting insecticidal nets plus
      indoor residual spraying, or PBO long-lasting insecticidal nets plus indoor
      residual spraying. Both standard and PBO nets were distributed in 2015. Indoor
      residual spraying was applied only once in 2015. We masked the inhabitants of
      each cluster to the type of nets received, as well as field staff who took blood
      samples. Neither the investigators nor the participants were masked to indoor
      residual spraying. The primary outcome was the prevalence of malaria infection in
      children aged 6 months to 14 years assessed by cross-sectional surveys at 4, 9,
      16, and 21 months after intervention. The endpoint for assessment of indoor
      residual spraying was 9 months and PBO long-lasting insecticidal nets was 21
      months. This trial is registered with ClinicalTrials.gov, number NCT02288637.
      FINDINGS: 7184 (68.0%) of 10 560 households were selected for post-intervention
      survey, and 15 469 (89.0%) of 17 377 eligible children from the four surveys were
      included in the intention-to-treat analysis. Of the 878 households visited in the
      two indoor residual spraying groups, 827 (94%) had been sprayed. Reported use of
      long-lasting insecticidal nets, across all groups, was 15 341 (77.3%) of 19 852
      residents after 1 year, decreasing to 12 503 (59.2%) of 21 105 in the second
      year. Malaria infection prevalence after 9 months was lower in the two groups
      that received PBO long-lasting insecticidal nets than in the two groups that
      received standard long-lasting insecticidal nets (531 [29%] of 1852 children vs
      767 [42%] of 1809; odds ratio [OR] 0.37, 95% CI 0.21-0.65; p=0.0011). At the same
      timepoint, malaria prevalence in the two groups that received indoor residual
      spraying was lower than in groups that did not receive indoor residual spraying
      (508 [28%] of 1846 children vs 790 [44%] of 1815; OR 0.33, 95% CI 0.19-0.55;
      p<0.0001) and there was evidence of an interaction between PBO long-lasting
      insecticidal nets and indoor residual spraying (OR 2.43, 95% CI 1.19-4.97;
      p=0.0158), indicating redundancy when combined. The PBO long-lasting insecticidal
      net effect was sustained after 21 months with a lower malaria prevalence than the
      standard long-lasting insecticidal net (865 [45%] of 1930 children vs 1255 [62%]
      of 2034; OR 0.40, 0.20-0.81; p=0.0122). INTERPRETATION: The PBO long-lasting
      insecticidal net and non-pyrethroid indoor residual spraying interventions showed
      improved control of malaria transmission compared with standard long-lasting
      insecticidal nets where pyrethroid resistance is prevalent and either
      intervention could be deployed to good effect. As a result, WHO has since
      recommended to increase coverage of PBO long-lasting insecticidal nets. Combining
      indoor residual spraying with pirimiphos-methyl and PBO long-lasting insecticidal
      nets provided no additional benefit compared with PBO long-lasting insecticidal
      nets alone or standard long-lasting insecticidal nets plus indoor residual
      spraying. FUNDING: UK Department for International Development, Medical Research
      Council, and Wellcome Trust.

PMID- 29655500
TI  - Characteristics of refugee patients admitted to the emergency department.

PMID- 29655501
TI  - Acute streptococcal meningitis presenting as bilateral conductive hearing loss.
AB  - Bacterial meningitis is a relatively uncommon condition encountered in the
      emergency department and the constellation of symptoms varies. Hearing loss has
      been well documented in the literature as a complication of the disease process,
      but not as the presenting complaint. We describe a case of a 59-year-old female
      who presented to the emergency department with sudden onset bilateral hearing
      loss who was found to have S. pneumonia meningitis bacterial meningitis. Even
      with advances in therapy, bacterial meningitis still carries a significant
      mortality rate. Early diagnosis and treatment is critical to achieving good
      outcomes.

PMID- 29655499
TI  - Genetic Testing in Clinical Settings.
AB  - Genetic testing is used for screening, diagnosis, and prognosis of diseases
      consistent with a genetic cause and to guide drug therapy to improve drug
      efficacy and avoid adverse effects (pharmacogenomics). This In Practice review
      aims to inform about DNA-related genetic test availability, interpretation, and
      recommended clinical actions based on results using evidence from clinical
      guidelines, when available. We discuss challenges that limit the widespread use
      of genetic information in the clinical care setting, including a small number of
      actionable genetic variants with strong evidence of clinical validity and
      utility, and the need for improving the health literacy of health care providers
      and the public, including for direct-to-consumer tests. Ethical, legal, and
      social issues and incidental findings also need to be addressed. Because our
      understanding of genetic factors associated with disease and drug response is
      rapidly increasing and new genetic tests are being developed that could be
      adopted by clinicians in the short term, we also provide extensive resources for
      information and education on genetic testing.

PMID- 29655502
TI  - Effect of regional cerebral oximetry to estimate neurologic prognostic outcomes
      in patients administered targeted temperature management.
AB  - PURPOSE: The aim of our study is to research the role and efficacy of cerebral
      oximetry in predicting neurologic prognosis when applied during TTM to patients
      experiencing coma after CA. METHODS: This study was performed on surviving adult
      comatose patients after CA treated with TTM. The average scores of rSO2 was
      measured at 6h intervals for the first 2days and once a day for the following
      3days with a NIRS device during TTM. The CPC scale was used to define the
      neurologic outcomes of patients. We compared the correlations of rSO2 values
      between good (CPC 1-2) and poor (CPC 3-5) neurologic outcomes in CA patients.
      RESULTS: There was no statistically significant difference identified between the
      prognosis groups in terms of rSO2, CPR durations, hemoglobin values and admission
      body temperature (p>0.05). When the variation in rSO2 values over time is
      investigated, though there was no significant difference between the good and
      poor prognosis groups, it appeared to fall in the first 6h in both prognosis
      groups. The median NT-proBNP and lactate values were observed to be higher in the
      poor prognosis group. CONCLUSION: There is no significant correlation between
      rSO2 values and neurologic outcomes. Multimodal monitoring methods may be useful
      and further studies with a larger patient population are necessary in this area.

PMID- 29655503
TI  - Headache in a patient with influenza.
AB  - Complications from influenza have been documented in the literature, but this
      patient case represents a rare and potentially deadly result in an otherwise
      healthy adult. Providers in the emergency department should be vigilant when
      assessing patients with influenza symptoms and monitoring those that don't always
      present with common symptoms and complaints. This patient's cerebral edema and
      tonsillar herniation was life-threatening and was caused from the influenza B
      virus.

PMID- 29655504
TI  - Naloxone access among an urban population of opioid users.

PMID- 29655505
TI  - Midterm outcome of transcatheter versus surgical aortic valve replacement in low
      to intermediate risk patients: A meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Current guidelines recommend transcatheter aortic valve replacement
      (TAVR) in patients with severe symptomatic aortic stenosis (AS) who are not
      suitable for conventional surgical aortic valve replacement (SAVR). In light of
      the recent trend in performing TAVR in patients with lower risk profile, we
      assessed the midterm outcome comparing TAVR and SAVR for the treatment of
      patients with severe AS at low to intermediate risk. METHODS: PubMed, EBSCO, and
      Cochrane CENTRAL were systematically searched for randomized controlled trials
      that reported the clinical outcomes of TAVR versus SAVR in patients at low to
      intermediate surgical risk with at least 2 years of follow-up. Clinical endpoints
      including death, acute kidney injury, myocardial infarction, stroke, permanent
      pacemaker implantation, and life-threatening bleeding events were assessed.
      RESULTS: From 2000 to 2017, 4 clinical studies comprising 4355 patients were
      identified. At 2-year follow-up, TAVR was associated with similar rate of death
      from any cause (RR 0.86; 95%CI: 0.67-1.10), cardiovascular death (RR 0.88; 95%CI:
      0.73-1.06), and stroke (RR 0.97; 95%CI: 0.81-1.15). TAVR reduced incidence of
      bleeding events (RR 0.45; 95%CI: 0.28-0.73) and acute kidney injury (RR 0.48;
      95%CI: 0.25-0.93). However, TAVR was associated with higher rate of permanent
      pacemaker implantation (RR 3.01; 95%CI: 1.04-8.72). CONCLUSION: In patients at
      low to intermediate surgical risk, midterm clinical outcomes of TAVR were similar
      to SAVR in survival and stroke rate, superior in reducing life-threatening
      bleeding, acute kidney injury, and new-onset atrial fibrillation, but inferior in
      increasing permanent pacemaker implantation.

PMID- 29655506
TI  - Letter to the Editor: Response to Costa et al.

PMID- 29655508
TI  - Methodological standards in single-case experimental design: Raising the bar.
AB  - Single-case experimental designs (SCEDs), or small-n experimental research, are
      frequently implemented to assess approaches to improving outcomes for people with
      disabilities, particularly those with low-incidence disabilities, such as some
      developmental disabilities. SCED has become increasingly accepted as a research
      design. As this literature base is needed to determine what interventions are
      evidence-based practices, the acceptance of SCED has resulted in increased
      critiques with regard to methodological quality. Recent trends include
      recommendations from a number of expert scholars and institutions. The purpose of
      this article is to summarize the recent history of methodological quality
      considerations, synthesize the recommendations found in the SCED literature, and
      provide recommendations to researchers designing SCEDs with regard to essential
      and aspirational standards for methodological quality. Conclusions include
      imploring SCED to increase the quality of their experiments, with particular
      consideration regarding the applied nature of SCED research to be published in
      Research in Developmental Disabilities and beyond.

PMID- 29655507
TI  - Response to name and its value for the early detection of developmental
      disorders: Insights from autism spectrum disorder, Rett syndrome, and fragile X
      syndrome. A perspectives paper.
AB  - BACKGROUND: Responding to one's own name (RtN) has been reported as atypical in
      children with developmental disorders, yet comparative studies on RtN across
      syndromes are rare. AIMS: We aim to (a) overview the literature on RtN in
      different developmental disorders during the first 24 months of life, and (b)
      report comparative data on RtN across syndromes. METHODS AND PROCEDURES: In Part
      1, a literature search, focusing on RtN in children during the first 24 months of
      life with developmental disorders, identified 23 relevant studies. In Part 2, RtN
      was assessed utilizing retrospective video analysis for infants later diagnosed
      with ASD, RTT, or FXS, and typically developing peers. OUTCOMES AND RESULTS:
      Given a variety of methodologies and instruments applied to assess RtN, 21/23
      studies identified RtN as atypical in infants with a developmental disorder. We
      observed four different developmental trajectories of RtN in ASD, RTT, PSV, and
      FXS from 9 to 24 months of age. Between-group differences became more distinctive
      with age. CONCLUSIONS AND IMPLICATIONS: RtN may be a potential parameter of
      interest in a comprehensive early detection model characterising age-specific
      neurofunctional biomarkers associated with specific disorders, and contribute to
      early identification.

PMID- 29655509
TI  - Reduced Right Ventricular Fractional Area Change, Strain, and Strain Rate before
      Bidirectional Cavopulmonary Anastomosis is Associated with Medium-Term Mortality
      for Children with Hypoplastic Left Heart Syndrome.
AB  - BACKGROUND: Ventricular dysfunction is associated with increased morbidity and
      mortality in children with hypoplastic left heart syndrome. The aim of this study
      was to assess the diagnostic performance of conventional and speckle-tracking
      echocardiographic measures of right ventricular (RV) function before
      bidirectional cavopulmonary anastomosis palliation in predicting death or need
      for heart transplantation (HTx). METHODS: RV fractional area change (RVFAC) and
      longitudinal and circumferential strain and strain rate (SR) were measured in 64
      prospectively recruited patients with hypoplastic left heart syndrome from
      echocardiograms obtained before bidirectional cavopulmonary anastomosis surgery.
      The composite end point of death or HTx was examined. Receiver operating
      characteristic analysis was performed, and cutoff values optimizing sensitivity
      and specificity were derived. RESULTS: At a median follow-up of 5.0 years
      (interquartile range, 2.8-6.4 years), 13 patients meeting the composite end point
      had lower longitudinal strain and SR, circumferential SR, and RVFAC compared with
      survivors (n = 51). The conventional cutoff of RVFAC < 35% was specific for death
      or HTx (86%) but had poor sensitivity (46%), with an area under the curve of
      0.73. Speckle-tracking echocardiographic variables showed similar areas under the
      curve (range, 0.69-0.79), with negative predictive values >90%. Addition of
      speckle-tracking echocardiographic variables to RVFAC < 35% showed no added
      benefit. However, in a subpopulation of patients with RVFAC >= 35% (n = 44),
      those meeting the composite end point (n = 7) had lower longitudinal SR (median, 
      1.0 1/sec [interquartile range, -0.8 to -1.1 1/sec] vs -1.21/sec [interquartile
      range, -1.0 to -1.3 1/sec], P = .03). Interobserver reproducibility was superior
      for longitudinal strain and SR (intraclass correlation coefficient > 0.92)
      compared with RVFAC (intraclass correlation coefficient = 0.75). CONCLUSIONS:
      Children with hypoplastic left heart syndrome with normal RVFAC and ventricular
      deformation before bidirectional cavopulmonary anastomosis have a low likelihood
      of death or HTx in the medium term. In the presence of reduced RVFAC, speckle
      tracking echocardiography does not provide additional prognostic value. However,
      in patients with "normal" RVFAC, it may have a role in improving outcome
      prediction and warrants further investigation.

PMID- 29655510
TI  - Histopathological validation of optical coherence tomography findings of the
      coronary arteries.
AB  - Optical coherence tomography (OCT), a catheter-based imaging modality for the
      visualization of coronary arteries, is widely used during percutaneous coronary
      intervention to improve the understanding of the anatomy of coronary artery
      stenosis and to elucidate the mechanisms of atherosclerosis. In this review, we
      provide a short description of the histopathological validations of OCT for
      visualizing atherosclerotic plaques and vascular healing response after drug
      eluting stent (DES) implantation. Because OCT measures the intensity of light
      returning from within a tissue, tissue having a higher heterogeneity of optical
      index of refraction, such as microcalcification deposition and foam cell
      accumulation on the luminal surface, may exhibit stronger optical scattering that
      appears as a thin-cap fibroatheroma image. Furthermore, even if OCT shows exposed
      uncovered stent struts, some of the struts could be re-endothelialized. In our ex
      vivo histopathological experience, re-endothelialization at the surface of stent
      struts was confirmed by histopathological analysis, although OCT images showed
      exposed uncovered struts after DES implantation. Therefore, careful
      interpretation is required to assess tissue morphology and stent strut coverage
      by OCT.

PMID- 29655511
TI  - Long-Term Transcriptional Gene Silencing by RNA Viruses.
AB  - Long-term transcriptional gene silencing has been hampered by delivery issues. A
      potential solution is the application of RNA viruses that generate small RNAs
      without any DNA intermediate. Long-term therapy for various diseases is expected
      after a single administration.

PMID- 29655512
TI  - Hypothesis on the Synchronistic Evolution of Autotrophy and Heterotrophy.
AB  - All life on earth requires a source of energy and organic carbon. There has been
      a continuous debate on whether autotrophic or heterotrophic metabolism came
      first. A very similar discussion exists concerning the advent of oxygenic
      photosynthesis and aerobic respiration. I put forward the synchronistic evolution
      hypothesis supposing that all metabolic processes develop in a bidirectional
      manner from the very first. Bidirectionality is claimed to be intrinsic to the
      evolution of all metabolic processes as (i) all biochemical reactions and enzymes
      are per se bidirectional, (ii) substrates need to be regenerated, and (iii) flux
      regulation requires flexibility of direction. Autotrophy and heterotrophy are
      thus inherent to each other. A scenario for the synchronistic development of
      oxygenic photosynthesis and aerobic respiration is described.

PMID- 29655513
TI  - Force of Peer Mentorship for Persons With Spinal Cord Injury.

PMID- 29655514
TI  - Defining Adverse Intraoperative Events in the Context of "Acute Risk Change"
      Following Cardiac Surgery.

PMID- 29655515
TI  - The Year in Thoracic Anesthesia: Selected Highlights From 2017.

PMID- 29655516
TI  - PLGA/beta-TCP composite scaffold incorporating salvianolic acid B promotes bone
      fusion by angiogenesis and osteogenesis in a rat spinal fusion model.
AB  - Spinal disorders often require surgical treatment called spinal fusion to restore
      a stabilized spine where bone grafts are implanted for the fusion of adjacent
      vertebras. In this study, we developed a bioactive composite scaffold
      incorporated with salvianolic acid B (SB), an active component extracted from
      Danshen. This study aimed to evaluate the effects of SB-incorporated porous
      scaffold on spinal fusion models. The composite scaffolds composed of poly
      (lactic-co-glycolic acid) and tricalcium phosphate (PLGA/beta-TCP) were
      fabricated with low-temperature rapid prototyping technique, which incorporated
      SB at low (SB-L), middle (SB-M), high (SB-H) doses, and pure PLGA/beta-TCP as
      blank control (Con). The release profile of SB from the scaffolds was determined
      by high performance liquid chromatography. Osteoconductive and osteoinductive
      properties of the scaffolds were reflected by the osteogenic differentiation
      ability of rat primary mesenchymal stem cells. The angiogenesis was determined by
      the forming of tube-like structures resembling capillaries using endothelial cell
      line (EA hy9.26). A well-established spinal fusion model was used to evaluate the
      in vivo bony fusion. Animals were transplanted with scaffolds, or autografts from
      iliac crest as positive controls. Micro-computed tomography (CT) analysis, CT
      based angiography, manual palpation test, histomorphometry, and histology were
      performed after 8 weeks of transplantation. Results revealed that incorporated SB
      was steadily released from the scaffolds. The aliquot of released SB promoted
      osteogenesis and angiogenesis in vitro in a dose-dependent manner. In animal
      study, a dose-dependent effect of SB on new bone formation, mineral apposition
      rate, and vessel density within the scaffold were demonstrated. Manual palpation
      test showed little numerical improvement in fusion rate when compared with the
      blank controls. In summary, our results suggested that SB-incorporated PLGA/beta
      TCP composite scaffold could enhance bony fusion through the promotion of
      osteogenesis and angiogenesis.

PMID- 29655517
TI  - Integrating Pregnancy Prevention Into an HIV Counseling and Testing Program in
      Pediatric Primary Care.
AB  - PURPOSE: Certified health educator (CHE)-based HIV counseling and testing
      typically focus on HIV and sexually transmitted infection (STI) prevention only.
      A quality improvement initiative examined integrating assessment of reproductive
      life plans, counseling about pregnancy prevention, and contraception referral
      into a CHE-based HIV testing program. METHODS: Between February 2014 and January
      2017, in one urban pediatric primary care clinic serving patients aged 0-25, CHEs
      assessed sexual history, HIV risk, short-term (i.e., the next 6-12 months)
      pregnancy desire, and current contraception method and satisfaction among
      patients aged 13-25 who had ever had vaginal sex, using a standardized
      questionnaire. Data were analyzed using a de-identified administrative dataset
      that also tracked referrals to initiate contraception and actual method
      initiation. RESULTS: Of 1,211 patients, most (96%) reported no short-term
      pregnancy or partner pregnancy desire. Use of less effective or no contraception,
      as well as method dissatisfaction, was common. A high proportion of female
      patients referred to new methods opted for more effective methods (62%) and
      initiated these methods (76%); a high proportion of male patients opted for
      receipt of condoms (67%). Patients reporting short-term pregnancy desire reported
      higher rates of previous pregnancy and STIs. CONCLUSIONS: Program findings
      highlight the potential benefit of integrating assessment for and counseling
      about pregnancy prevention in a CHE-based HIV testing program. This can more
      effectively address the needs of patients with concomitant risks of STI/HIV and
      unintended pregnancy, and link patients who do not desire pregnancy to more
      effective methods.

PMID- 29655518
TI  - The American Journal of Ophthalmology Will Publish American Ophthalmological
      Society Theses.

PMID- 29655519
TI  - Much ado about mice: Standard-setting in model organism research.
AB  - Recently there has been a practice turn in the philosophy of science that has
      called for analyses to be grounded in the actual doings of everyday science. This
      paper is in furtherance of this call and it does so by employing participant
      observation ethnographic methods as a tool for discovering epistemological
      features of scientific practice in a neuroscience lab. The case I present focuses
      on a group of neurobiologists researching the genetic underpinnings of cognition
      in Down syndrome (DS) and how they have developed a new mouse model which they
      argue should be regarded as the "gold standard" for all DS mouse research.
      Through use of ethnographic methods, interviews, and analyses of publications, I
      uncover how the lab constructed their new mouse model. Additionally, I describe
      how model organisms can serve as abstract standards for scientific work that
      impact the epistemic value of scientific claims, regulate practice, and constrain
      future work.

PMID- 29655520
TI  - Comparing ultraviolet light A photo(chemo)therapy with Methotrexate protocol in
      childhood localized scleroderma: Evidence from systematic review and meta
      analysis approach.
AB  - OBJECTIVE: Localized scleroderma is a skin fibrosing disorder that, if untreated,
      may result in severe disability. The purpose of this systematic review is to
      compare the present evidence concerning the effectiveness of Methotrexate versus
      phototherapy, alone or associated with Psoralen, in childhood localized
      scleroderma. METHOD: A systematic search between January 1996 and May 2017 was
      performed to identify studies investigating the efficacy of Methotrexate (MTX) or
      phototherapy (UVA) for treating localized scleroderma with onset <=18 years. Due
      to a lack of validated clinical criteria, four clinical response criteria were
      used to assess the treatment efficacy as primary outcome. We determined a
      combined estimate of the proportion of children responding to MTX and UVA.
      RESULTS: A total of 19 studies was included (8 MTX; 11 UVA). In the methotrexate
      group, 193 children were included in the analysis; in the phototherapy group, a
      total of 48 treated children. For both groups age, disease subtype,
      glucocorticoids (GCs) use, and side effects of treatment were also analyzed. The
      meta-analysis suggested that UVA and MTX protocols have both a favorable effect
      in active lesions of childhood localized scleroderma. However, MTX resulted
      significantly superior to UVA, with or without Psoralen. CONCLUSION: Our study
      supports the combination of MTX and GCs in patients with a high risk of
      complication. Phototherapy with UVA1 could represent a therapeutic option in
      patients with limited scleroderma, where lesions do not cross joints and they do
      not lead to potential cosmetic changes.

PMID- 29655521
TI  - Spontaneous acute subdural hematoma. An unusual presentation of ruptured cerebral
      aneurysm.

PMID- 29655522
TI  - Antibiotics as Instigators of Microbial Dysbiosis: Implications for Asthma and
      Allergy.
AB  - The human body and its resident microbiota form a complex ecosystem, shaped by
      both inherited and environmental factors. The use of antibiotics represents an
      extreme example of environmental pressure and can broadly disrupt the microbial
      landscape. The benefits that antibiotics have brought to modern medicine are
      unquestionable; however, their overuse comes with consequences, including the
      potential for secondary infections by opportunistic pathogens and the spread of
      antibiotic resistance. Here, we discuss the implications of microbial dysbiosis
      driven by antibiotics, with a focus on potential links with allergy and asthma.
      We review epidemiological data on humans, as well as mechanistic studies
      performed in animal models, and highlight gaps in current knowledge, which if
      addressed, could drive the design of novel therapeutic strategies and improved
      clinical care.

PMID- 29655523
TI  - The clinical value of HPV E6/E7 and STAT3 mRNA detection in cervical cancer
      screening.
AB  - OBJECTIVE: To explore the value of human papillomavirus (HPV) E6/E7 and signal
      transducer and activator of transcription 3 (STAT3) mRNA detection in the
      screening of cervical lesions. METHODS: 192 patients with abnormal ThinPrep
      cytology test (TCT) results and/or high-risk HPV infection were screened to
      identify possible cervical lesions in cases. Diagnoses were confirmed by
      histopathology. Fluorescence in situ hybridization (FISH) was performed to detect
      and qualify the mRNAs of HPV E6/E7, STAT3, and Survivin in cervical exfoliated
      cells. In addition, the performance of separate and combined mRNA detection
      methods were compared with TCT, HR-HPV DNA schemes respectively. RESULTS: 1.
      Compared with HPVE6/E7 and STAT3 mRNA methods, Survivin mRNA assay had poor
      specificity (Sp), Youden index (YI) and concordance rate. 2. HPV E6/E7, STAT3,
      and STAT3 + HR-HPV methods had the best Sp, concordance rate and positive
      predictive value (PPV) for cervical lesions screening and atypical squamous cells
      of undetermined significance (ASCUS) triage. For screening of high grade squamous
      intraepithelial lesions or greater (HSILs+), no difference was observed in the Se
      of mRNA detection methods in comparison with that of TCT, HR-HPV and TCT + HR
      HPV, whereas the false positive rate (FPR) decreased by 41.48%/55.99%/17.19% and
      the colposcopy referral rate reduced by about 20.00%/25.00%/11.17%. For triage of
      women with ASCUS, no difference was observed in the Se of mRNA detection methods
      as compared to that of HR-HPV (chi2 = 1.05, P > 0.75), while the FPR decreased by
      45.83%/37.50%/41.66% and the colposcopy referral rate reduced by
      32.42%/22.60%/25.28%, respectively. The Se, YI, and PPV of the combined methods
      increased in comparison to each method alone. 3. Compared with the TCT + HR-HPV
      method, HPV E6/E7 + STAT3 method had perfect Sp (95.92%) and PPV (95.40%) for
      screening HSILs+, the FPR and colposcopy referral rate decreased by 31.06% and
      22.48% respectively. CONCLUSIONS: 1. The expression of HPV E6/E7 and STAT3 mRNA
      confirmed using FISH assay is expected to be a new method and molecular marker
      for cervical lesions screening. Survivin mRNA was excluded due to its poor
      performance. 2. HPV E6/E7, STAT3, and STAT3 +HR-HPV assays could be new
      approaches for cervical cancer screening and ASCUS triage, and the efficiency of
      combined screening program was better than that of a separate one. 3. HPV E6/E7 +
      STAT3 regimen is expected to be a diagnostic strategy for cervical lesions.

PMID- 29655524
TI  - Poliosis With a Rare Association.

PMID- 29655525
TI  - Predictive value of liver damage for severe early complications and survival
      after heart transplantation: A retrospective analysis.
AB  - BACKGROUND: Hepatic dysfunction is often associated with advanced heart failure.
      Its impact on complications following heart transplantation is not well known. We
      studied the influence of preoperative hepatic dysfunction on the results of heart
      transplantation with a specific priority access for critical patients. METHODS:
      Consecutive heart transplantation patients were retrospectively analyzed at
      listing to detect predictive factors for early complications and survival
      following heart transplantation. RESULTS: Among heart transplant candidates
      (n=384), median age was 52 years, dilated and ischemic cardiopathies were present
      in 44% and 32%, respectively. Clinical ascites was present in 15.6% and median
      MELD score was 13. A temporary circulatory support and a national priority access
      were necessary in 14.8% and 35% respectively. Whereas 12% of the global cohort
      died on the waiting list, 321 patients were transplanted, 34.2% suffered from
      severe early complications, 26.3% needed extracorporeal membrane oxygenation in
      postoperative period, 27.7% died before 3 months with a 5-year survival rate of
      56%. At listing, clinical ascites, and creatinine were independently associated
      with specific early complications i.e. primary graft dysfunction and septic shock
      respectively. Bilirubin level was also an independent marker of other early
      complications. Finally, need for postoperative circulatory support and
      postoperative 90-day mortality were strongly and exclusively associated with
      clinical ascites and creatinine at listing. In a subgroup analysis, we predicted
      more accurately the postoperative survival at 3 months by combining MELD score
      and ascites. CONCLUSION: At listing, hepatic and renal dysfunctions are
      independent risk factors that could predict severe early complications and
      mortality following heart transplantation in the most severe patients.

PMID- 29655526
TI  - Association between appendectomy and risk of primary sclerosing cholangitis: A
      systematic review and meta-analysis.
AB  - BACKGROUND/OBJECTIVES: Recent epidemiologic studies have suggested that
      appendectomy could be a risk factor for primary sclerosing cholangitis (PSC)
      although the results were inconsistent. This systematic review and meta-analysis
      was conducted to summarize all available evidence. METHODS: A comprehensive
      literature review was conducted using MEDLINE and EMBASE database through January
      2018 to identify all studies that reported the risk of PSC among individuals who
      had appendectomy versus those with no history of appendectomy. Effect estimates
      from each study were extracted and combined together using the random-effect,
      generic inverse variance method of DerSimonian and Laird. RESULTS: A total of 6
      case-control studies with 2432 participants met the eligibility criteria and were
      included in the meta-analysis. The risk of PSC in individuals who had
      appendectomy was significantly higher than those with no history of appendectomy
      with the pooled odds ratio of 1.37 (95% CI: 1.15-1.63). The statistical
      heterogeneity was insignificant with an I2 of 0%. CONCLUSIONS: A significantly
      increased risk of PSC among individuals who had a history of appendectomy was
      found in this study.

PMID- 29655527
TI  - The smiling scan technique: Facially driven guided surgery and prosthetics.
AB  - PURPOSE: To introduce a proof of concept technique and new integrated workflow to
      optimize the functional and esthetic outcome of the implant-supported
      restorations by means of a 3-dimensional (3D) facially-driven, digital assisted
      treatment plan. METHODS: The Smiling Scan technique permits the creation of a
      virtual dental patient (VDP) showing a broad smile under static conditions. The
      patient is exposed to a cone beam computed tomography scan (CBCT), displaying a
      broad smile for the duration of the examination. Intraoral optical surface
      scanning (IOS) of the dental and soft tissue anatomy or extraoral optical surface
      scanning (EOS) of the study casts are achieved. The superimposition of the
      digital imaging and communications in medicine (DICOM) files with standard
      tessellation language (STL) files is performed using the virtual planning
      software program permitting the creation of a VDP. CONCLUSIONS: The smiling scan
      is an effective, easy to use, and low-cost technique to develop a more
      comprehensive and simplified facially driven computer-assisted treatment plan,
      allowing a prosthetically driven implant placement and the delivery of an
      immediate computer aided design (CAD) computer aided manufacturing (CAM)
      temporary fixed dental prostheses (CAD/CAM technology).

PMID- 29655528
TI  - A mobile app for patients with Pompe disease and its possible clinical
      applications.
AB  - In recent years, the potential of smart technology to provide innovative
      solutions for disease management has raised high expectations for patients' and
      healthcare professionals' community. We developed a mobile app, called AIGkit,
      specifically designed for adult patients with Pompe disease, with the aim to help
      them manage the burden of illness-related factors, and also to provide clinicians
      with continuous tracking of each patient in real-time and ambient conditions of
      everyday life. We present the AIGkit as an innovative approach exploiting cutting
      edge technology to improve quality of care and research into neuromuscular
      disorders.

PMID- 29655529
TI  - 233rd ENMC International Workshop:: Clinical Trial Readiness for Calpainopathies,
      Naarden, The Netherlands, 15-17 September 2017.

PMID- 29655530
TI  - Lifetime endogenous estrogen exposure and disease severity in female patients
      with facioscapulohumeral muscular dystrophy.
AB  - Facioscapulohumeral muscular dystrophy (FSHD) is characterized by large
      variability in disease severity, that is only partly explained by (epi)genetic
      factors. Clinical observations and recent in vitro work suggest a protective
      effect of estrogens in FSHD. The aims of this study were to assess whether the
      lifetime endogenous estrogen exposure contributes to the variability in disease
      severity in female patients, and whether female patients experience changes in
      disease progression during periods of hormonal changes. We calculated the
      lifetime endogenous estrogen exposure by subtracting periods with high
      progesterone levels (in which estrogens are counteracted) from the reproductive
      life span. Multiple linear regression in 85 patients did not show a contribution
      of the lifetime endogenous estrogen exposure to disease severity (B = 0.063, P
      value = 0.517, DeltaR2 = 0.003). The majority of women reported an unchanged rate
      of disease progression through periods of hormonal changes, like menarche,
      pregnancy or menopause. Women that noticed differences reported accelerations as
      well as decelerations. These results indicate that differences in estrogen
      exposure do not have a clinically relevant modifying effect on disease severity.
      However, a clinically relevant protective effect of greater differences in
      estrogen levels, or a protective effect caused by a more complex interplay with
      other reproductive hormones, cannot be ruled out.

PMID- 29655531
TI  - Food insecurity and Mediterranean diet adherence among Greek university students.
AB  - AIM: To assess Mediterranean diet (MD) adherence and food insecurity (FI) among
      university students in Greece. METHODS AND RESULTS: A non-probability sample of
      236 students was recruited from Athens and Thessaloniki during 2016. FI was
      assessed with the Household Food Insecurity Access Scale and MD adherence with
      the MEDAS questionnaire. Mean MEDAS score of the sample was 6.4 +/- 1.9, with
      women demonstrating greater MD adherence compared to men (p = 0.016) and
      Dietetics students exhibiting increased score compared to the rest (p <= 0.001).
      A low proportion of participants were food-secure (17.8%), 45.3% were severely
      food-insecure, 22.0% experienced moderate FI and the remaining 14.8% had low FI.
      Participants studying in the city they grew up exhibited lower FI compared to
      those studying in other cities (p = 0.009), while, additionally, a trend was
      noted for increased FI among students with an unemployed family member (p =
      0.05). Students working night shifts had lower MD adherence and increased FI
      compared to the rest (p = 0.004 and p = 0.003, respectively). The same pattern
      was observed among participants who smoked (p = 0.003 for MD adherence and p =
      0.009 for FI, respectively). Multivariate regression analyses did not reveal any
      connections between FI categories, waist circumference or BMI, but showed an
      inverse relationship between severe FI and MD adherence. CONCLUSIONS: The
      majority of the surveyed university students from Greece demonstrate some degree
      of FI, with a great proportion being severely food-insecure. Increased FI is
      inversely associated with MD adherence.

PMID- 29655532
TI  - Evaluation of different therapeutic Carnoy's formulations on hard human tissues:
      A Raman microspectroscopy, microhardness, and scanning electron microscopy study.
AB  - PURPOSE: To evaluate different therapeutic Carnoy's solution formulations on hard
      human tissues. MATERIALS AND METHODS: An in vitro study was performed with human
      teeth (n = 36) and bone fragments (n = 18), randomly divided into two
      experimental groups (Group I = Carnoy solution with chloroform; Group II = Carnoy
      solution without chloroform) and a control group (saline solution). The groups
      were subdivided into pre-conditioning, post-conditioning, and post-conditioning
      with saline washing. Raman microspectroscopy, Knoop microhardness test, and
      scanning electron microscopy with energy dispersive X-ray spectroscopy were used.
      RESULTS: There was demineralization of dental structures regarding mineral/matrix
      and carbonate/phosphate ratios (GI versus GII, p < 0.05). The presence of
      chloroform resulted in a statistically significant reduction of the teeth surface
      microhardness (p = 0.036), but not exceeding 0.01 MUm. Both GI and GII showed
      significant structural changes by using scanning electron microscopy with energy
      dispersive X-ray spectroscopy. CONCLUSION: Carnoy's solution altered the organic
      and inorganic matrix of the human calcified specimens analyzed in vitro, and its
      effect was more pronounced when chloroform was present.

PMID- 29655533
TI  - QSPR modeling of the logKow and logKoc of polymethoxylated, polyhydroxylated
      diphenyl ethers and methoxylated-, hydroxylated-polychlorinated diphenyl ethers.
AB  - In the present study, the structural parameters of 209 types of polymethoxylated
      diphenyl ethers (PMeODEs), 209 types of polyhydroxylated diphenyl ethers
      (PHODEs), seven types of methoxylated-polychlorinated diphenyl ethers (MeO-PCDEs)
      and seven types of hydroxylated-polychlorinated diphenyl ethers (HO-PCDEs) were
      calculated using the Gaussian 09 program at the B3LYP/6-311G** level. Using
      structural and positional parameters as descriptors, quantitative structure
      property relationships (QSPR) models for the prediction of n-octanol/water
      partition coefficient (logKow) and soil sorption coefficient normalized to
      organic carbon (logKoc) were established and verified. The position parameters
      N2(6), N3(5) and N4 were the main positional factors influencing logKow and
      logKoc of PMeODEs and PHODEs. The molecular polarizability alpha was entered into
      the QSPR models of the logKow and logKoc of PMeODEs, PHODEs and MeO/HO-PCDEs,
      indicating that the molecular volume could influence the two environment-related
      properties of DEs significantly. All of the established QSPR models showed good
      goodness-of-fit, robustness, and predictive ability. The two models for all of
      the tested DEs are slightly inferior compared with the models for only a class of
      compounds. In addition, application domain analysis indicated that the models
      reliably predicted the logKow and logKoc of the mon- to hexa-DEs.

PMID- 29655534
TI  - Comparison of constant, pulsed, incremental and decremental direct current
      applications on solid-liquid phase separation in oil sediments.
AB  - Phase separation of oil wastes can mitigate the effects on the environment, by
      decreasing the volume of hazardous materials and regenerate energy. This study
      focused on the advanced electrokinetic method as a treatment technology to treat
      oil sediments from oil refineries and separate them into their individual phase
      components. The effects of four types of electrical field on the phase separation
      of oil sediments from an oil refinery were investigated namely constant direct
      current (CDC), pulsed direct current (PDC), incremental direct current (IDC) and
      decremental direct current (DDC). The results showed that the extent and quality
      of phase separation differed based on the type of electrical current applied, and
      indicated that different mechanisms such as electroosmosis, electrophoresis,
      electro-demulsification, and electro-sedimentation might have been involved in
      the separation process depending on the type of electrical supply. The
      application of DDC and IDC was found to cause a significant separation of solids
      by electrophoresis with the movement of almost 70% of solids to the anode of the
      reactors. The DDC and IDC regimes resulted in the most efficient phase separation
      of the oil sediments, and even incurred a highly resolved separation of light
      hydrocarbons at the top anode.

PMID- 29655535
TI  - Laser induced breakdown in gas mixtures. Experimental and statistical
      investigation on n-decane ignition: Pressure, mixture composition and equivalence
      ratio effects.
AB  - This paper presents a physical and statistical approach to laser-induced
      breakdown in n-decane/N2 + O2 mixtures as a function of incident or absorbed
      energy. A parametric study, with pressure, fuel purity and equivalence ratio, was
      conducted to determine the incident and absorbed energies involved in producing
      breakdown, followed or not by ignition. The experiments were performed using a Q
      switched Nd-YAG laser (1064 nm) inside a cylindrical 1-l combustion chamber in
      the range of 1-100 mJ of incident energy. A stochastic study of breakdown and
      ignition probabilities showed that the mixture composition had a significant
      effect on ignition with large variation of incident or absorbed energy required
      to obtain 50% of breakdown. It was observed that the combustion products absorb
      more energy coming from the laser. The effect of pressure on the ignition
      probabilities of lean and near stoichiometric mixtures was also investigated. It
      was found that a high ignition energy E50% is required for lean mixtures at high
      pressures (3 bar). The present study provides new data obtained on an original
      experimental setup and the results, close to laboratory-produced laser ignition
      phenomena, will enhance the understanding of initial conditions on the breakdown
      or ignition probabilities for different mixtures.

PMID- 29655536
TI  - Anemia, transfusion, and outcome: Both are bad...does it really matter which is
      worse?

PMID- 29655537
TI  - Ambulatory extracorporeal membrane oxygenation as a bridge to cardiac transplant:
      A step in the right direction?

PMID- 29655538
TI  - Occam's razor: What is the best approach for a lobectomy?

PMID- 29655539
TI  - Month-long cardiac surgery boot camp: A proposal to jumpstart resident training.

PMID- 29655540
TI  - Extra-anatomic suprahepatic to innominate vein conduit in heterotaxy.

PMID- 29655541
TI  - Finding the sweet spot: Titrating unfractionated heparin in children after
      cardiac surgery to prevent thrombosis and minimize bleeding.

PMID- 29655542
TI  - Finally, seeing the forest for the trees.

PMID- 29655543
TI  - It's not just an open or shut case.

PMID- 29655544
TI  - Innovations in cardiovascular surgical technique: Separating the wheat from the
      chaff.

PMID- 29655545
TI  - Seeing more clearly despite the ptosis.

PMID- 29655546
TI  - Late left ventricular rupture as a complication of NeoChord implantation for
      mitral valve repair.

PMID- 29655547
TI  - Is venoarterial extracorporeal membrane oxygenation the first-line therapy for
      massive pulmonary embolus with end-organ dysfunction?

PMID- 29655548
TI  - The good, the bad and the ugly-or how to treat complications of complications.

PMID- 29655549
TI  - From hydroelectric power to Fontan assistance: (R)evolution of the turbine.

PMID- 29655550
TI  - Proteomic investigating the cooperative lethal effect of EGFR and MDM2 inhibitors
      on ovarian carcinoma.
AB  - With the concept of precision medicine, combining multiple molecular-targeting
      therapies has brought new approaches to current cancer treatments. Malfunction of
      the tumor suppressor protein, p53 is a universal hallmark in human cancers. Under
      normal conditions, p53 is degraded through an ubiquitin-proteosome pathway
      regulated by its negative regulator, MDM2. In contrast, cellular stress such as
      DNA damage will activate p53 to carry out DNA repair, cell cycle arrest, and
      apoptosis. In this study, we focused on ovarian carcinoma with high EGFR and MDM2
      overexpression rate. We assessed the effects of combined inhibition by MDM2 (JNJ
      26854165) and EGFR (gefitinib) inhibitors on various ovarian cell lines to
      determine the importance of these two molecular targets on cell proliferation. We
      then used a proteomic strategy to investigate the relationship between MDM2 and
      EGFR inhibition to explore the underlying mechanisms of how their combined
      signaling blockades work together to exert cooperative inhibition. Our results
      demonstrated that all four cell lines were sensitive to both individual and
      combined, MDM2 and EGFR inhibition. The proteomic analysis also showed that
      gefitinib/JNJ-treated CAOV3 cells exhibited downregulation of proteins involved
      in nucleotide biosynthesis such as nucleoside diphosphate kinase B (NME2). In
      conclusion, our study showed that the combined treatment with JNJ and gefitinib
      exerted synergistic inhibition on cell proliferation, thereby suggesting the
      potential application of combining MDM2 inhibitors with EGFR inhibitors for
      enhancing efficacy in ovarian cancer treatment.

PMID- 29655552
TI  - Binge eating disorder and morbid obesity are associated with lowered mu-opioid
      receptor availability in the brain.
AB  - Both morbid obesity and binge eating disorder (BED) have previously been linked
      with aberrant brain opioid function. Behaviorally these two conditions are
      however different suggesting also differences in neurotransmitter function. Here
      we directly compared mu-opioid receptor (MOR) availability between morbidly obese
      and BED subjects. Seven BED and nineteen morbidly obese (non-BED) patients, and
      thirty matched control subjects underwent positron emission tomography (PET) with
      MOR-specific ligand [11C]carfentanil. Both subjects with morbid obesity and BED
      had widespread reduction in [11C]carfentanil binding compared to control
      subjects. However, there was no significant difference in brain MOR binding
      between subjects with morbid obesity and BED. Thus, our results indicate that
      there is common brain opioid abnormality in behaviorally different eating
      disorders involving obesity.

PMID- 29655551
TI  - Medical and entomological malarial interventions, a comparison and synergy of two
      control measures using a Ross/Macdonald model variant and openmalaria simulation.
AB  - Using an established Ross/Macdonald model variant for mosquito-born parasite
      transmission, we extend the formalism to simply incorporate time-dependent
      control measures. In particular, two interventions are considered, mass drug
      administration (MDA) and indoor residual spraying (IRS), whose individual
      intensities during their respective campaigns are set to the same intervention
      reduced reproductive number R0. The impacts of these interventions, measured as
      each campaign's ability over time to reduce infections in a community, are found
      based on the transmission setting, coverage, and their associated durations.
      These impacts are compared for both interventions and their joint deployment.
      Synchronous campaigns of IRS deployed with MDA have a cooperative, synergistic
      effect whose impact exceeds that when the campaigns are deployed in isolation.
      Simulations with openmalaria, with its more complex model of transmission, are
      separately performed and show a similar impact enhancement with these
      interventions. A new, associated analysis yields simple scaling relationships
      that estimate the dynamical resurgence time, post-intervention, to infection
      proliferation in a community.

PMID- 29655553
TI  - Transitional care post TAVI: A pilot initiative focused on bridging gaps and
      improving outcomes.
AB  - Interventions focused on ensuring safe transitions for patients from hospital to
      home can assist in providing continuity of care, preventing readmissions, and
      reducing duplication of services. Patients undergoing a Transcatheter Aortic
      Valve Implantation (TAVI) procedure are often frail, elderly, and have multiple
      co-morbidities. A pilot initiative evaluating transitional care strategies
      through telephone follow up was implemented in a tertiary centre with the aim to
      identify gaps and intervene, preventing re-admission and improving patient
      outcomes. TAVI patients or caregivers were contacted at 3 days and 30 days post
      discharge by an Advanced Practice Nurse (APN). Telephone follow up centered on
      best practices for transitional care. Outcomes revealed fluid balance monitoring,
      medication management, and feelings of anxiety and depression post TAVI were the
      most frequent areas requiring intervention. Findings from this initiative
      reinforce the need to establish consistent processes that support elderly patient
      populations during potentially vulnerable points in the care trajectory.

PMID- 29655554
TI  - UK Consensus on Normal Tissue Dose Constraints for Stereotactic Radiotherapy:
      Reply to Ghafoor et al.

PMID- 29655555
TI  - Effects of treatment of preweaning dairy calves with recombinant bovine
      somatotropin on immune responses and somatotropic axis.
AB  - Weaning may be associated with negative energy balance and body weight loss when
      calves are still immunologically immature, predisposing them to infectious
      diseases. The aim of the present experiment was to investigate the effects of
      treatment of preweaning dairy calves with recombinant bovine somatotropin (rbST)
      on the somatotropic axis, selected immune parameters, and hematology of calves
      around weaning. Thirty-six Holstein female calves were randomly assigned to
      receive 1.5 to 1.8 mg of rbST (Posilac, Elanco Animal Health, Greenfield, IN) per
      kilogram of body weight or to receive injections of saline (saline solution 0.9%,
      Valley Vet Supply, Marysville, KS) every 7 d from 21 to 63 d of life. Calves were
      fed milk replacer ad libitum from birth to 38 d of age (d -11), when progressive
      weaning started, and calves were weaned at 49 d of age (d 0). Calves were weighed
      at birth and weekly from 21 to 63 d of age, when wither height also was measured.
      Calves were vaccinated with 0.5 mg of ovalbumin on study d -28 and -7. Blood
      samples were collected on d -28, -25, -21, -11, 0, 3, 7, and 14.
      Polymorphonuclear leukocytes were isolated and challenged ex vivo with
      Escherichia coli to determine phagocytosis and oxidative burst capacity.
      Additionally, expression of cluster of differentiation (CD)62L and CD18 by
      granulocyte, lymphocyte, and CD14+ monocyte were determined. Blood samples were
      also used to determine hematological parameters and concentrations of growth
      hormone, insulin-like growth factor-1, insulin, glucose, fatty acids, beta
      hydroxybutyrate, haptoglobin, and anti-ovalbumin IgG. Calves treated with rbST
      had greater concentrations of growth hormone and insulin-like growth factor-1
      from d -25 to 14 than control calves, whereas insulin, fatty acid, and beta
      hydroxybutyrate concentrations did not differ. On d -11, glucose concentration
      was greater for rbST-treated calves. Treatment did not affect polymorphonuclear
      lymphocyte phagocytosis and oxidative burst, but intensity of expression of CD62L
      and CD18 by granulocytes tended to be increased by rbST treatment. Treatment did
      not affect the concentration of anti-ovalbumin IgG in serum. Haptoglobin
      concentration was reduced in rbST treated calves on d 3 and we noted a tendency
      for hematocrit to be lower in rbST-treated calves. Treatment did not affect body
      weight, wither height, and average daily gain, despite the fact that rbST-treated
      calves had lower daily milk replacer intake. The relatively minor improvements in
      immune responses resulting from rbST treatment of weaning calves may not be
      sufficient to reduce the incidence of infectious diseases.

PMID- 29655556
TI  - In vitro bioassessment of the immunomodulatory activity of Saccharomyces
      cerevisiae components using bovine macrophages and Mycobacterium avium ssp.
      paratuberculosis.
AB  - The yeast Saccharomyces cerevisiae and its components are used for the prevention
      and treatment of enteric disease in different species; therefore, they may also
      be useful for preventing Johne's disease, a chronic inflammatory bowel disease of
      ruminants caused by Mycobacterium avium ssp. paratuberculosis (MAP). The
      objective of this study was to identify potential immunomodulatory S. cerevisiae
      components using a bovine macrophage cell line (BOMAC). The BOMAC phagocytic
      activity, reactive oxygen species production, and immune-related gene (IL6, IL10,
      IL12p40, IL13, IL23), transforming growth factor beta, ARG1, CASP1, and inducible
      nitric oxide synthase expression were investigated when BOMAC were cocultured
      with cell wall components from 4 different strains (A, B, C, and D) and 2 forms
      of dead yeast from strain A. The BOMAC phagocytosis of mCherry-labeled MAP was
      concentration-dependently attenuated when BOMAC were cocultured with yeast
      components for 6 h. Each yeast derivative also induced a concentration-dependent
      increase in BOMAC reactive oxygen species production after a 6-h exposure. In
      addition, BOMAC mRNA expression of the immune-related genes was investigated
      after 6 and 24 h of exposure to yeast components. All yeast components were found
      to regulate the immunomodulatory genes of BOMAC; however, the response varied
      among components and over time. The in vitro bioassessment studies reported here
      suggest that dead yeast and its cell wall components may be useful for modulating
      macrophage function before or during MAP infection.

PMID- 29655557
TI  - An evaluation of the effectiveness of a chemical additive based on sodium
      benzoate, potassium sorbate, and sodium nitrite on the fermentation and aerobic
      stability of corn silage.
AB  - We evaluated the effectiveness of an additive comprising sodium benzoate,
      potassium sorbate, and sodium nitrite (SSL) as active ingredients for its ability
      to improve the aerobic stability of corn silages made in North America. In
      experiment 1, treatment with SSL (1.5 and 2.0 L/t) on whole-plant corn (WPC) was
      compared with treatment with an additive containing buffered propionic acid and
      citric acid (BPA; 2 L/t) on corn harvested at 32 and 38% dry matter and ensiled
      for 120 d. Silage treated with BPA was higher in ammonia-N and propionic acid
      relative to other treatments. Treatments with all of the additives had
      numerically, but not statistically, fewer yeasts compared with untreated silage.
      Both application rates of SSL resulted in lower concentrations of ethanol
      compared with untreated and BPA silages. Treatment with BPA improved the aerobic
      stability of silages compared with untreated silage, but the effect from SSL was
      markedly greater. In experiment 2, WPC was untreated or treated with 2 or 3 L of
      SSL/t or a microbial inoculant containing Enterococcus faecium M74, Lactobacillus
      plantarum CH6072, and Lactobacillus buchneri LN1819 (final total lactic acid
      bacteria application rate of 150,000 cfu/g of fresh forage). Silages were air
      stressed for 24 h at 28 and 42 d of storage and ensiled for 49 d before opening.
      Inoculation had no effect on acid end products, ethanol, number of yeasts, or
      aerobic stability compared with other treatments. Treatment with SSL decreased
      the amount of ethanol, had no effect on number of yeasts, and improved aerobic
      stability in a dose-dependent manner compared with other treatments. In
      experiment 3, WPC was untreated or treated with 2 L of SSL/t and ensiled for 5,
      15, and 30 d. Treatment with SSL resulted in silage with fewer yeasts and lower
      concentrations of ethanol after all times of ensiling compared with untreated
      silage. In addition, SSL improved aerobic stability after each period of
      ensiling, but the effect was more at 15 and 30 d compared with 5 d of storage.
      Treating WPC with SSL can improve the aerobic stability of corn silage made in
      North America, and the effect can be observed as soon as 5 d after ensiling.

PMID- 29655558
TI  - Effects of feeding milk replacer at 2 rates with pelleted, low-starch or
      texturized, high-starch starters on calf performance and digestion.
AB  - Milk replacer (MR) feeding programs have traditionally fed at less than ad
      libitum amounts to promote calf starter (CS) intake and allow early weaning. More
      recently, increased amounts of MR preweaning have been shown to increase
      preweaning ADG, although postweaning growth may be reduced. Several studies
      suggest that limited postweaning digestion of nutrients in CS may contribute to
      postweaning growth impairment. It is not clear whether CS formulation might also
      contribute to differences in postweaning nutrient digestion when calves are fed
      different MR programs. A 56-d feeding and digestion trial was conducted to
      compare growth and digestion in 2- to 3-d-old male Holstein calves (n = 48;
      initially 41.9 kg of body weight) fed a moderate (MRM) or high (MRH) MR program
      and either a pelleted CS containing 9.9% starch or a texturized CS containing
      41.3% starch. Programs were 0.66 kg of dry matter (DM)/d of MR to d 46, then 0.33
      kg/d to d 49 (MRM) and 0.85 kg of DM/d to d 5, then 1.07 kg/d to d 42, then 0.53
      kg/d to d 49 (MRH). The MR contained 25% crude protein and 18.6% fat and was
      reconstituted to 13 (MRM) or 15% (MRH) solids. Calves were also assigned randomly
      to receive a pelleted CS (9.9% starch, 36.9% NDF) or a textured CS (41.3% starch,
      13.3% NDF) and water for ad libitum intake for 56 d. During d 31 to 35 and 52 to
      56, fecal samples were collected from 5 calves per treatment for estimates of
      digestibility. Selected nutrients and chromic oxide (d 31-35) or acid-insoluble
      ash (d 52-56) were analyzed in feed and feces to estimate digestibility. Data
      were analyzed as a completely randomized design. Repeated measures analysis was
      performed when data were measured by week. Calves fed MRH gained more body weight
      (but not hip width) and were more efficient to weaning compared with calves fed
      MRM, although fecal scores and days treated with medications were greater. We
      found no effect of CS on animal performance, although calves fed textured CS had
      higher fecal scores. Digestibilities of nutrients were affected by treatment and
      time of sampling (5 or 8 wk). At 5 wk, digestion of DM, organic matter, crude
      protein, and fat were lower and digestion of acid detergent fiber, neutral
      detergent fiber, and starch were higher in calves fed MRM and reflected greater
      CS intake. Also, digestion of DM, organic matter, acid detergent fiber, starch,
      crude protein, and fat were greater in calves fed textured CS at 5 wk. By 8 wk,
      when CS was the only source of nutrients, digestion of DM, organic matter, acid
      detergent fiber, and neutral detergent fiber were greater in calves fed MRM and
      digestion of DM and organic matter were greater, and acid detergent fiber and
      neutral detergent fiber digestion were lower in calves fed textured CS.
      Formulation of CS as well as amount of MR offered to young calves influenced
      animal performance and digestion in this study.

PMID- 29655559
TI  - Associations between bone and energy metabolism in cows fed diets differing in
      level of dietary cation-anion difference and supplemented with cholecalciferol or
      calcidiol.
AB  - Bone-derived hormones play an important role in metabolism. This study examined
      the hypothesis that interactions between bone and energy metabolism, particularly
      those involving osteocalcin, are present in dairy cattle and have feedback
      mechanisms over time. Associations between metabolites in blood were examined in
      32 Holstein cows blocked by parity and milk yield and randomly allocated to diets
      containing either 0.27 mg/kg dry matter (DM) calcidiol or cholecalciferol for an
      anticipated intake of 3 mg/d (120,000 IU/d) at 11 kg of DM, and positive (+130
      mEq/kg DM) or negative (-130 mEq/kg DM) dietary cation-anion difference (DCAD)
      from 252 d of gestation to calving. Blood was sampled every 3 d, from 9 d
      prepartum to 30 d postpartum, and plasma concentrations of vitamin D3, 25
      hydroxyvitamin D3, adiponectin, C-telopeptide of type 1 collagen (CTX1), glucose,
      insulin-like growth factor 1 (IGF1), insulin, undercarboxylated osteocalcin
      (uOC), and carboxylated osteocalcin (cOC) were determined. Feeding calcidiol
      compared with cholecalciferol increased plasma concentrations of 25
      hydroxyvitamin D3 pre- (264.2 +/- 8.0 vs. 61.3 +/- 8.0 ng/mL) and postpartum
      (170.8 +/- 6.2 vs. 51.3 +/- 6.2 ng/mL) but decreased concentrations of vitamin D3
      pre- (1.2 +/- 0.6 vs. 14.5 +/- 0.6 ng/mL) and postpartum (1.9 +/- 0.4 vs. 3.2 +/-
      0.6 ng/mL). Prepartum, cows fed the negative DCAD diet had reduced concentrations
      of vitamin D3 and glucose compared with cows fed a positive DCAD. The combination
      of negative DCAD and cholecalciferol reduced IGF1 concentrations prepartum. The
      DCAD treatment had no effect on postpartum concentrations of metabolites.
      Nulliparous cows had increased concentrations of OC, CTX1, IGF1, glucose, and
      insulin compared with parous cows. Time series analysis identified associations
      between metabolites on the same day and over 3-d lags up to +/-9 d that suggest
      feedback between 25-hydroxyvitamin D3 and vitamin D3 in the negative lags,
      indicating that 25-hydroxyvitamin D3 may exert feedback on vitamin D3 but not
      vice versa. We found evidence of a feedback mechanism between vitamin D3 and
      IGF1, with positive effect size (ES) on the same day and 3 d later, and negative
      ES 9 d later, that was more evident in cholecalciferol-fed cows. This suggests an
      important role of IGF1 in integrating bone metabolism with energy and protein
      metabolic pathways. Evidence of feedback was found between uOC and particularly
      cOC with IGF1, with positive ES on the same day but negative ES 6 d before and 6
      d after. An association between uOC or cOC and IGF1 has not been previously
      identified in cattle and suggests that both uOC and cOC may have marked
      biological activity. Associations between OC and insulin identified in mice were
      not observed herein, although associations between OC and glucose were similar to
      those between IGF1 and glucose, supporting associations between glucose, OC, and
      IGF1. We provide further statistical evidence of crosstalk between vitamin D
      compounds, bone hormones, and energy metabolism in cattle. In particular,
      associations between uOC or cOC and IGF1 may provide links between prepartum
      diets and observations of prolonged increases in milk production and allow better
      control of peripartum metabolism.

PMID- 29655560
TI  - Selected reaction monitoring mass spectrometry of mastitis milk reveals pathogen
      specific regulation of bovine host response proteins.
AB  - Mastitis is a major challenge to bovine health. The detection of sensitive
      markers for mastitis in dairy herds is of great demand. Suitable biomarkers
      should be measurable in milk and should report pathogen-specific changes at an
      early stage to support earlier diagnosis and more efficient treatment. However,
      the identification of sensitive biomarkers in milk has remained a challenge, in
      part due to their relatively low concentration in milk. In the present study, we
      used a selected reaction monitoring (SRM) mass spectrometry approach, which
      allowed the absolute quantitation of 13 host response proteins in milk for the
      first time. These proteins were measured over a 54-h period upon an in vivo
      challenge with cell wall components from either gram-negative (lipopolysaccharide
      from Escherichia coli; LPS) or gram-positive bacteria (peptidoglycan from
      Staphylococcus aureus; PGN). Whereas our data clearly demonstrate that all
      challenged animals have consistent upregulation of innate immune response
      proteins after both LPS and PGN challenge, the data also reveal clearly that LPS
      challenge unleashes faster and shows a more intense host response compared with
      PGN challenge. Biomarker candidates that may distinguish between gram-negative
      and gram-positive bacteria include alpha-2 macroglobulin, alpha-1 antitrypsin,
      haptoglobin, serum amyloid A3, cluster of differentiation 14, calgranulin B,
      cathepsin C, vanin-1, galectin 1, galectin 3, and IL-8. Our approach can support
      further studies of large cohorts of animals with natural occurring mastitis, to
      validate the relevance of these suggested biomarkers in dairy production.

PMID- 29655561
TI  - Interaction between the physical forms of starter and forage source on growth
      performance and blood metabolites of Holstein dairy calves.
AB  - The objective of this study was to investigate the effects of the physical forms
      of starter and forage sources on feed intake, growth performance, rumen pH, and
      blood metabolites of dairy calves. Forty male Holstein calves (41.3 +/- 3.5 kg of
      body weight) were used (n = 10 calves per treatment) in a 2 * 2 factorial
      arrangement of treatments with the factors being physical forms of starter
      (coarse mash and texturized) and forage source [alfalfa hay (AH) and wheat straw
      (WS)]. Individually housed calves were randomly assigned to 1 of the 4 dietary
      treatments, including (1) coarsely mashed (CM; coarse ground grains combined with
      a mash supplement) starter feed with AH (CM-AH), (2) coarsely mashed starter feed
      with WS (CM-WS), (3) texturized feed starter (TF; includes steam-flaked corn,
      steam-rolled barley combined with a pelleted supplement) with AH (TF-AH), and (4)
      TF with WS (TF-WS). Both starters had the same ingredients and nutrient
      compositions but differed in their physical forms. Calves were weaned on d 56 and
      remained in the study until d 70. All calves had free access to drinking water
      and the starter feeding at all times. No interaction was detected between the
      physical forms of starter feeds and forage source concerning starter intake, dry
      matter intake, metabolizable energy (ME) intake, average daily gain (ADG)/ME
      intake, ADG, and feed efficiency (FE). The preweaning and overall starter feed
      intake, dry matter intake, and ME intake were greater for calves fed TF starter
      diets than those fed CM starter diets. The ADG/ME intake was greater for calves
      fed TF starter diets than that fed CM starter. The FE was greater for calves fed
      TF starter diets compared with those fed CM starter during the preweaning,
      postweaning, and overall periods. The WS improved FE during the postweaning
      period compared with AH. The physical form of starter, forage source, and their
      interaction did not affect plasma glucose, triglycerides, and very low-density
      lipoprotein concentrations. Ruminal pH was greater for calves fed TF starter
      diets than those fed CM starter on d 30 of life. An interaction was observed
      between the physical forms of starter diets and forage source for beta
      hydroxybutyrate on d 28. These results showed that when starter diets contained
      similar ingredients and nutrient contents, processing calf starters to reduce the
      number of fine particles can improve the growth performance in dairy calves.
      Furthermore, the provision of WS improved FE and ADG of calves during the
      postweaning period.

PMID- 29655562
TI  - Quantification of bovine leukemia virus proviral DNA using a low-cost real-time
      polymerase chain reaction.
AB  - The detection of bovine leukemia virus (BLV) proviral DNA is an important tool to
      address whether an animal is infected with BLV. Compared with serological assays,
      real-time PCR accounts for greater sensitivity and can serve as a confirmatory
      test for the clarification of inconclusive or discordant serological test
      results. However, the high cost related to real-time PCR assays has limited their
      systematic inclusion in BLV surveillance and eradication programs. The aim of the
      present study was to validate a low-cost quantitative real-time PCR.
      Interestingly, by using SYBR Green detection dye, we were able to reduce the cost
      of a single reaction by a factor of 5 compared with most common assays based on
      the use of fluorogenic probes (i.e., TaqMan technology). This approach allowed a
      highly sensitive and specific detection and quantification of BLV proviral DNA
      from purified peripheral blood leukocytes and a milk matrix. Due to its
      simplicity and low cost, our in-house BLV SYBR quantitative real-time PCR might
      be used either as a screening or as a confirmatory test in BLV control programs.

PMID- 29655563
TI  - Laboratory evaluation of a novel rapid tube test system for differentiation of
      mastitis-causing pathogen groups.
AB  - Because clinical mastitis, one of the most common diseases in dairy cows, is
      routinely treated with antimicrobial substances, it offers a high potential for
      future reduction of antimicrobial usage. In fact, intramammary antibiotic
      administration is not advisable in cases of clinical mastitis caused by coliform
      bacteria, yeasts, or protothecae or in cases with no detectable mastitis
      pathogen. To avoid unnecessary treatments with antimicrobials for the benefit of
      animal health and public welfare, the rapid identification of the mastitis
      causing pathogens becomes necessary. Therefore, 4 different incubation time
      schemes for a newly developed tube test system (MastDecide, Quidee GmbH, Homberg,
      Germany) were analyzed in terms of sensitivity, specificity, negative and
      positive predictive values, and apparent and true prevalence compared with the
      conventional microbiological investigation results for 251 clinical mastitis milk
      samples from 11 dairy farms located in northern Germany. An aliquot (100 uL) of a
      quarter foremilk sample was taken in both cases. The evaluation of the tube test
      result after 14 h of incubation at 37 degrees C resulted in sensitivity values of
      83.6, 72.2, and 70.7% and specificity values of 94.1, 83.3, and 90.8% for gram
      positive cocci, coliform bacteria, and no growth or further pathogens,
      respectively. Moreover, for the present pathogen distribution, the overall tube
      test sensitivity was highest after 14 h of incubation (sensitivity = 80.9%;
      specificity = 70.7%). The described tube test system has the potential to provide
      a new option for an evidence-based mastitis therapy, with the aim of reducing the
      future usage of antimicrobials in dairy cows and a larger goal of decreasing
      antimicrobial resistance. However, a subsequent on-farm test validation should be
      performed before implementation in an evidence-based mastitis therapy concept can
      be recommended.

PMID- 29655564
TI  - Feeding reduced-fat dried distillers grains with solubles to lactating Holstein
      dairy cows does not alter milk composition or cause late blowing in cheese.
AB  - Feeding dried distillers grains with solubles (DDGS) to lactating dairy cows has
      been implicated as a cause of late blowing defects in the production of Swiss
      style cheeses. Our objectives were (1) to test the effect of feeding reduced-fat
      DDGS (RF-DDGS; ~6% fat) to lactating dairy cows on the composition of milk and on
      the suitability of the milk for production of baby Swiss cheese and (2) to
      evaluate the effect of diet on cow lactation performance. Lactating Holstein
      dairy cows were fed both dietary treatments in a 2 * 2 crossover design. Cows
      were housed in a 48-cow freestall pen equipped with individual feeding gates to
      record feed intake. The control diet was a corn, corn silage, and alfalfa hay
      diet supplemented with mechanically expelled soybean meal. The experimental diet
      was the same base ration, but 20% (dry matter basis) RF-DDGS were included in
      place of the expelled soybean meal. The RF-DDGS diet was additionally
      supplemented with rumen-protected lysine; diets were formulated to be
      isoenergetic and isonitrogenous. Cows were allowed ad libitum access to feed and
      water, fed twice daily, and milked 3 times daily. For cheese production, milk was
      collected and pooled 6 times for each dietary treatment. There was no treatment
      effect on milk yield (35.66 and 35.39 kg/d), milk fat production (1.27 and 1.25
      kg/d), milk fat percentage (3.65 and 3.61%), milk protein production (1.05 and
      1.08 kg/d), lactose percentage (4.62 and 4.64%), milk total solids (12.19 and
      12.28%), and somatic cell count (232.57 and 287.22 * 103 cells/mL) for control
      and RF-DDGS, respectively. However, dry matter intake was increased by treatment,
      which implied a reduction in feed efficiency. Milk protein percentage also
      increased (3.01 and 3.11%), whereas milk urea nitrogen decreased (14.18 and 12.99
      mg/dL), indicating that protein utilization may be more efficient when cows are
      fed RF-DDGS. No differences in cheese were observed by a trained panel except
      cheese appearance; control cheese eyes were significantly, but not practically,
      larger than the RF-DDGS cheese. These results indicate that RF-DDGS can be
      effectively used in the rations of lactating Holstein cows with no deleterious
      effects on milk production and composition and metrics of the physiology of the
      cow (i.e., blood glucose and nonesterified fatty acids); however, feeding RF-DDGS
      increased dry matter intake, which decreased feed efficiency. Finally, feeding RF
      DDGS did not negatively influence quality and suitability of milk for production
      of baby Swiss cheese.

PMID- 29655565
TI  - The tolerogenic role of IFN-gamma.
AB  - Due to its extremely pleiotropic nature, the complex effects of IFN-gamma exerted
      both on immune and non-immune cell types still remain only partially understood.
      The longstanding view of IFN-gamma as being a predominantly inflammatory cytokine
      is constantly challenged by increasing demonstrations of its direct or indirect
      regulatory roles. Interferon-gamma can exert tolerogenic effects on both innate
      and adaptive immune cell types, promoting tolerance of various antigen-presenting
      cells, and augmenting function and differentiation of regulatory T cells,
      respectively. Its capacity to induce IDO-competence is not limited to immune
      cells but extends to other cell types such as mesenchymal stem cells, epithelial
      cells, and tumors. The pro-inflammatory role of IFN-gamma in tumor immune
      surveillance can backfire by directly inducing inhibitory molecule expression,
      such as PDL-1, on tumor cells. With increasing knowledge regarding the role of
      different helper T cell subsets in certain autoimmune diseases, the once
      contradictory observations of disease attenuation by IFN-gamma can now be
      explained by its opposing interplay with other effector cytokines, particularly
      IL-17. The paradoxically immunosuppressive role of IFN-gamma is also becoming
      evident in the transplantation setting, and graft-versus-host-disease. In the
      present review, we will discuss the latest findings that help to elucidate this
      dual role of IFN-gamma at a cellular level, and in various pathophysiological
      states.

PMID- 29655566
TI  - Development of MR quantified pancreatic fat deposition as a cancer risk
      biomarker.
AB  - BACKGROUND: Excess body adiposity is associated with increased risk of pancreatic
      cancer, and in animal models excess intra-pancreatic fat is a driver of
      pancreatic carcinogenesis. Within a programme to evaluate pancreatic fat and PC
      risk in humans, we assessed whether MR-quantified pancreatic fat fraction (PFF)
      was 'fit for purpose' as an imaging biomarker. METHODS: We determined PFF using
      MR spectroscopy (MRS) and MR chemical shift imaging (CS-MR), in two groups. In
      Group I, we determined accuracy of MR-derived PFF with histological digital fat
      quantification in 12 patients undergoing pancreatic resection. In a second study,
      we assessed reproducibility in 15 volunteers (Group IIa), and extended to 43
      volunteers (Group IIa & IIb) to relate PFF with MR-derived hepatic fat fraction
      (HFF), body mass index (BMI), and waist circumference (WC) using linear
      regression models. We assessed intra- and inter-observer, and between imaging
      modality levels of agreement using Bland-Altman plots. RESULTS: In Group I
      patients, we found strong levels of agreement between MRS and CS-MR derived PFF
      and digitally quantified fat on histology (rho: 0.781 and 0.672 respectively). In
      Group IIa, there was poor reproducibility in initial assessments. We refined our
      protocols to account for 3D dimensionality of the pancreas, and found
      substantially improved intra-observer agreements. In Group II, HFF and WC were
      significantly correlated with PFF (p values < 0.05). INTERPRETATION: Both CS-MR
      and MRS (after accounting for pancreatic 3D dimensionality) were 'fit for
      purpose' to determine PFF and might add information on cancer prediction
      independent from measures of general body adiposity.

PMID- 29655567
TI  - Acute coronary syndrome: Relationship between genetic variants and TIMI risk.
AB  - Acute Coronary Syndrome (ACS) is a multifactorial disease, including the genetic
      factor, caused by coronary artery obstruction by atheroma. Some genetic variants
      have been described as risk factors for this disease. Its early diagnosis and
      stratification of risk of death by Thrombolysis in Myocardial Infarction (TIMI)
      are important. Therefore, we evaluated variants in the IL6R (c950-1722C>T), TNFa
      (c.-488G>A), LEPR (c.2673+1118C>T) and IL1b (c.-598T>C) genes in relation to TIMI
      risk, cytokine serum levels, and risk factors for ACS. We selected 200 patients
      with ACS, 50 without ACS from the Real Hospital Portugues, Recife - PE, and 295
      blood donors at the Fundacao de Hematologia e Hemoterapia de Pernambuco (Hemope).
      Variants were determined by DNA sequencing or enzymatic cleavage. Cytokine levels
      were measured by ELISA. The most frequent risk factors found in the patients were
      dyslipidemia and hypertension, this latter associated with high TIMI risk (p =
      0.003). Genotype frequencies of IL6R and TNFa differed between patients with ACS
      and the blood donors (p = 0.0002 and p = 0.01, respectively), and TNF-alpha
      levels differed between genotypes. The TT genotype of the IL6R gene is as a
      possible protective factor for ACS because it was significantly more present in
      blood donors (32.2%) than in patients with ACS (18.0%), and was more frequent in
      low TIMI risk (22.9%) than in the intermediate (20.2%) or high (4.9%). In
      patients with ACS, the TT genotype in IL6R was related to a lower concentration
      of c-reactive protein (p = 0.03) and troponin (p = 0.02), showing a less
      inflammatory reaction and tissue damage. The differences in the frequencies of
      variants in genes of medical interest among the groups show the importance of
      studies in specific populations groups to establish the relationship between
      genes and diseases.

PMID- 29655568
TI  - Luteolin attenuates acute lung injury in experimental mouse model of sepsis.
AB  - The present investigation was undertaken to assess the result of pretreatment of
      luteolin in sepsis-induced acute lung injury in mice and its mechanism of action.
      Luteolin was administered intraperitoneally one hour before caecal ligation and
      puncture (CLP) surgery in mice. Acute lung injury was assessed by estimation of
      different parameters like lung edema, protein content, cytokines level, oxidative
      stress, inducible nitric oxide synthase (iNOS), intercellular adhesion molecule
      (ICAM)-1 expression and histopathology. Pretreatment of mice with luteolin showed
      decrease lung edema and protein content in tissue and bronchoalveolar lavage
      fluid (BALF). However, mice pretreated with luteolin showed reduction (p = 0.92)
      in blood and lung tissue bacterial counts however it was non significant.
      Further, luteolin showed significant reduction in interleukin (IL)-6 and IL-1beta
      in lung tissue which are the proinflammatory cytokines. However, plasma IL-1beta
      and tissue tumor necrosis factor (TNF)-alpha level decrease (p = 0.24; p = 0.19)
      with this pretreatment. Further, ICAM-1 mRNA expression and nuclear factor (NF)
      kappa B protein expression were significantly (p < 0.01) decreased in luteolin
      pretreated septic mice. The lung iNOS level, iNOS mRNA and protein expressions
      were markedly (p = 0.25; p = 0.50; p = 0.06) altered with luteolin pretreatment,
      respectively. Also, significant reduction in lipid peroxidation and increase in
      the activity of antioxidant enzymes like superoxide dismutase (SOD) and catalase
      was noted with luteolin pretreatment. However, luteolin did not alter (p = 0.36)
      the non enzymatic antioxidant GSH activity in septic mice. Histopathology of lung
      tissue showed reduction in lung injury with the luteolin pretreatment in septic
      mice. The study suggests that luteolin showed attenuation in sepsis-induced acute
      lung injury in mice through suppression in ICAM-1, NF-kappa B, oxidative stress
      and partially iNOS pathways.

PMID- 29655569
TI  - Activation of the porcine alveolar macrophages via toll-like receptor 4/NF-kappaB
      mediated pathway provides a mechanism of resistin leading to inflammation.
AB  - Resistin, a previously discovered cysteine-rich adipokine known to regulate
      glucose metabolism, has been emerged as a mediator in inflammation and immunity.
      Its level was supposed to be related to the expression of indicators, such as
      interleukin-1beta (IL-1beta), IL-6 and tumor necrosis factor-alpha (TNF-alpha) in
      inflammation. Toll-like receptor 4 (TLR4) was reported to be a receptor for
      resistin in cells, like leukocytes and peripheral blood mononuclear cells (PBMC).
      However, the pro-inflammatory role of resistin and its intracellular mechanisms
      in alveolar macrophages have not been thoroughly validated. Here we found that
      the pro-inflammatory cytokine expression in porcine alveolar macrophages (PAMs)
      was positively correlated with resistin. Our results also showed that resistin
      induced the expression of TLR4, intracellular molecules myeloid differentiation
      primary response protein 88 (MyD88), TRIF-related adaptor molecule (TRAM) and
      nuclear factor kappaB (NF-kappaB) in PAMs. In contrast, inhibition of TLR4,
      MyD88, TRAM and NF-kappaB abrogated the pro-inflammatory effect of resistin on
      PAMs. Additionally, the associations among TLR4, MyD88/TRAM and NF-kappaB were
      investigated by introducing TLR4-siRNA, MyD88-siRNA and TRAM-siRNA respectively
      into PAMs prior to the treatment with resistin. Taken together, our findings
      demonstrated that resistin promoted the production of pro-inflammatory cytokine
      in PAMs via TLR4/NF-kappaB-mediated pathway (TLR4/MyD88/TRAM/NF-kappaB).

PMID- 29655570
TI  - Interleukin-7 enhances anti-tumor activity of CD8+ T cells in patients with
      hepatocellular carcinoma.
AB  - Interleukin (IL)-7 stimulation improves virus- and tumor-specific CD8+ T cell
      responses. However, the role of IL-7 in modulation of dysfunctional CD8+ T cells
      in hepatocellular carcinoma (HCC) was not completely understood. In this study, a
      total of 37 HLA-A2 restricted patients with HCC and 16 healthy individuals were
      enrolled. IL-7 expression and its receptor alpha chain CD127 level was measured.
      The regulatory activity of IL-7 to peripheral and liver-resident CD8+ T cells was
      investigated in co-culture systems which were directly or indirectly contacted
      with HCC cell line HepG2 in vitro. Serum IL-7 concentration was significantly
      reduced in HCC patients, while effective anti-tumor treatment up-regulated IL-7
      expression. However, CD127 expression was comparable on peripheral CD8+ T cells
      from either HCC patients and healthy individuals, and was also similar on liver
      resident CD8+ T cells from either normal tissues and HCC specimens. CD8+ T cells
      purified from normal liver tissues also presented stronger cytotoxicity compared
      with those from HCC specimens prior to and post IL-7 treatment. Moreover, IL-7
      stimulation not only augmented cytotoxicity of peripheral and liver-resident CD8+
      T cells, but also promoted IFN-gamma and TNF-alpha production by CD8+ T cells in
      direct contact co-culture system. This process was accompanied by down-regulation
      of programmed death-1 (PD-1) expression on CD8+ T cells. Our present data
      indicated that IL-7 enhanced both cytolytic and noncytolytic activity of CD8+ T
      cells to HCC probably via repression of PD-1 under direct tumor cells
      presentation. IL-7 might be considered as one of the therapeutic candidates for
      HCC treatment.

PMID- 29655571
TI  - A Rapid Access Chest Pain Clinic (RACPC): Initial Australian Experience.
AB  - BACKGROUND: Chest pain is the second most common presenting symptom to emergency
      departments (ED) in Australia, although up to 85% of these patients do not have
      an acute coronary syndrome (ACS). Cardiologist-led rapid access chest pain
      clinics (RACPC) have been proposed overseas to assist in the management of such
      patients, with prompt outpatient assessment if patients are deemed low risk and
      discharged from the ED. The use of RACPCs in Australia has been only recently
      proposed; we therefore sought to examine one such RACPC in an Australian context.
      METHODS AND RESULTS: 1133 consecutive patients were seen at a metropolitan RACPC,
      between August 2008 and February 2017. There was a high preponderance of
      cardiovascular risk factors. Exercise stress testing (EST) was the default
      investigation upon discharge from ED, with a total of 1038 ESTs performed in 1113
      patients (93%), with low numbers of other functional tests, and a small, but
      increasing number of coronary computed tomography (CT) scans performed over this
      period. Eighteen patients subsequently underwent revascularisation (1.6% of the
      total cohort), and none of these patients were readmitted at any time with an ACS
      between the interval of their index ED presentation to these investigations or
      treatments. Five (0.4%) patients represented to ED within 48hours, none due to a
      cardiovascular cause. A total of 24 (2.1%) patients represented between 2 and 28
      days, with none of these due to an ACS. CONCLUSIONS: Following ED assessment of
      acute chest pain as low risk-with direct ED referral for exercising testing
      followed by RACPC review-results in very low readmission rates at 48hours and at
      28 days. Moreover, these readmissions were almost always not of cardiovascular
      aetiology, and occurred despite relatively longer waiting periods for both EST (8
      days) and between EST and RACPC review (11 days), than the prespecified 72 to
      96hours as defined by the clinic protocol. Further investigation into this model
      of care in Australia is suggested.

PMID- 29655572
TI  - 3D Modelling and Printing Technology to Produce Patient-Specific 3D Models.
AB  - BACKGROUND: A comprehensive knowledge of mitral valve (MV) anatomy is crucial in
      the assessment of MV disease. While the use of three-dimensional (3D) modelling
      and printing in MV assessment has undergone early clinical evaluation, the
      precision and usefulness of this technology requires further investigation. This
      study aimed to assess and validate 3D modelling and printing technology to
      produce patient-specific 3D MV models. METHODS: A prototype method for MV 3D
      modelling and printing was developed from computed tomography (CT) scans of a
      plastinated human heart. Mitral valve models were printed using four 3D printing
      methods and validated to assess precision. Cardiac CT and 3D echocardiography
      imaging data of four MV disease patients was used to produce patient-specific 3D
      printed models, and 40 cardiac health professionals (CHPs) were surveyed on the
      perceived value and potential uses of 3D models in a clinical setting. RESULTS:
      The prototype method demonstrated submillimetre precision for all four 3D
      printing methods used, and statistical analysis showed a significant difference
      (p<0.05) in precision between these methods. Patient-specific 3D printed models,
      particularly using multiple print materials, were considered useful by CHPs for
      preoperative planning, as well as other applications such as teaching and
      training. CONCLUSIONS: This study suggests that, with further advances in 3D
      modelling and printing technology, patient-specific 3D MV models could serve as a
      useful clinical tool. The findings also highlight the potential of this
      technology to be applied in a variety of medical areas within both clinical and
      educational settings.

PMID- 29655573
TI  - [The reality on peritoneal dialysis in France: 40years after].
AB  - The share of peritoneal dialysis (PD) in the spectrum of chronic dialysis has
      decreased in France over the last ten years. Despite various facilities offered
      by the health authorities, PD remains confidential in many private units and some
      public hospitals. The enthusiasm present at the beginning of this technology,
      forty years ago, is declining, despite a real improvement in new developments, a
      real increase in patient survival, today at least similar to that on
      hemodialysis. Then, the aim of this review is first to give a summary of the
      principles and practice of patient and staff education and to describe the role
      of the medical contribution in decision-making. The second aim is to review
      patient and technique survival data of PD patients henceforth prolonged, and the
      new insights into dialysis adequacy. The presence of residual renal function is a
      main determinant of patient comfort together with prevention of over-hydratation.
      Improvement of the peritoneal catheter is underlined. The prevention and
      management of infections is reviewed, and also the regular assessment of
      peritoneal function. Free water transport is a predictor of encapsulating
      peritoneal sclerosis, which should be assessed regularly. The physiopathology and
      the pathogenesis of this devastating complication allow now the prevention, and a
      better treatment.

PMID- 29655574
TI  - Current treatment for non-alcoholic fatty liver disease.
AB  - Non-alcoholic fatty liver disease is the most prevalent hepatopathy, estimated at
      30% in the general population. In the coming years, it will likely be the most
      common indication for liver transplantation and the most frequent cause of
      hepatocellular carcinoma. Current treatment for non-alcoholic fatty liver disease
      is based on dietary and exercise interventions that have been shown to be
      efficacious, even for reverting fibrosis. Unfortunately, compliance with general
      measures involving lifestyle modifications is very poor, making pharmacologic
      strategies a necessary option. At present, there are no treatments for non
      alcoholic fatty liver disease approved by regulatory agencies, and the only ones
      with sufficient evidence and recommended by international societies are
      treatments with pioglitazone and vitamin E, which are not exempt from adverse
      effects. We review herein the current management of non-alcoholic fatty liver
      disease, including dietary and physical activity interventions, available
      treatments, equivocal therapies, emerging treatments, and treatments presently in
      clinical trials.

PMID- 29655576
TI  - [Endophthalmitis secondary to keratomycosis of unusual etiology: Scytalidium
      hyalinum].

PMID- 29655575
TI  - CRMP2-Neurofibromin Interface Drives NF1-related Pain.
AB  - An understudied symptom of the genetic disorder Neurofibromatosis type 1 (NF1) is
      chronic idiopathic pain. We used targeted editing of Nf1 in rats to provide
      direct evidence of a causal relationship between neurofibromin, the protein
      product of the Nf1 gene, and pain responses. Our study data identified a protein
      interaction network with collapsin response meditator protein 2 (CRMP2) as a node
      and neurofibromin, syntaxin 1A, and the N-type voltage-gated calcium (CaV2.2)
      channel as interaction edges. Neurofibromin uncouples CRMP2 from syntaxin 1A.
      Upon loss/mutation of neurofibromin, as seen in patients with NF1, the
      CRMP2/Neurofibromin interaction is uncoupled, which frees CRMP2 to interact with
      both syntaxin 1A and CaV2.2, culminating in increased release of the pro
      nociceptive neurotransmitter calcitonin gene-related peptide (CGRP). Our work
      also identified the CRMP2-derived peptide CNRP1, which uncoupled CRMP2's
      interactions with neurofibromin, syntaxin 1A, as well as CaV2.2. Here, we tested
      if CRISPR/Cas9-mediated editing of the Nf1 gene, which leads to functional
      remodeling of peripheral nociceptors through effects on the tetrodotoxin
      sensitive (TTX-S) Na+ voltage-gated sodium channel (NaV1.7) and CaV2.2, could be
      affected using CNRP1, a peptide designed to target the CRMP2-neurofibromin
      interface. The data presented here shows that disrupting the CRMP2-neurofibromin
      interface is sufficient to reverse the dysregulations of voltage-gated ion
      channels and neurotransmitter release elicited by Nf1 gene editing. As a
      consequence of these effects, the CNRP1 peptide reversed hyperalgesia to thermal
      stimulation of the hindpaw observed in Nf1-edited rats. Our findings support
      future pharmacological targeting of the CRMP2/neurofibromin interface for NF1
      related pain relief.

PMID- 29655577
TI  - [Bilateral Peters anomaly without glaucoma].

PMID- 29655578
TI  - [Retinoblastoma metastatic to the parotid gland: A case report].

PMID- 29655579
TI  - Hungarian tick-borne encephalitis viruses isolated from a 0.5-ha focus are
      closely related to Finnish strains.
AB  - Four tick-borne encephalitis virus strains were isolated from a small 0.5-ha
      focus over a six-year-long period (2011-2016) in Hungary. Two strains with
      identical genomes were isolated from Ixodes ricinus and Haemaphysalis concinna
      two months apart, which shows that the virus had not evolved separately in these
      tick species. Whole-genome sequencing of the virus revealed that the isolates
      differed from each other in 4 amino acids and 9 nucleotides. The calculated
      substitution rates indicated that the speed of genome evolution differs from
      habitat to habitat, and continuously changes even within the same focus. The
      amino acid changes affected the capsid, envelope, NS2a and NS5 genes, and one
      mutation each occurred in the 5' and 3' NCR as well as the premembrane, NS2a and
      NS5 genes. Phylogenetic analyses based on complete coding ORF sequences showed
      that the isolates belong to the European subtype of the virus and are closely
      related to the Finnish Kumlinge strains, the Bavarian isolate Leila and two
      isolates of Russian origin, but more distantly related to viruses from the
      neighbouring Central European countries. These isolates obviously have a common
      origin and are probably connected by migrating birds. These are the first
      published complete Hungarian TBEV sequences.

PMID- 29655580
TI  - Canadian Association of Radiologists White Paper on Artificial Intelligence in
      Radiology.
AB  - Artificial intelligence (AI) is rapidly moving from an experimental phase to an
      implementation phase in many fields, including medicine. The combination of
      improved availability of large datasets, increasing computing power, and advances
      in learning algorithms has created major performance breakthroughs in the
      development of AI applications. In the last 5 years, AI techniques known as deep
      learning have delivered rapidly improving performance in image recognition,
      caption generation, and speech recognition. Radiology, in particular, is a prime
      candidate for early adoption of these techniques. It is anticipated that the
      implementation of AI in radiology over the next decade will significantly improve
      the quality, value, and depth of radiology's contribution to patient care and
      population health, and will revolutionize radiologists' workflows. The Canadian
      Association of Radiologists (CAR) is the national voice of radiology committed to
      promoting the highest standards in patient-centered imaging, lifelong learning,
      and research. The CAR has created an AI working group with the mandate to discuss
      and deliberate on practice, policy, and patient care issues related to the
      introduction and implementation of AI in imaging. This white paper provides
      recommendations for the CAR derived from deliberations between members of the AI
      working group. This white paper on AI in radiology will inform CAR members and
      policymakers on key terminology, educational needs of members, research and
      development, partnerships, potential clinical applications, implementation,
      structure and governance, role of radiologists, and potential impact of AI on
      radiology in Canada.

PMID- 29655581
TI  - Paternal Understanding of Menstrual Concerns in Young Women.
AB  - STUDY OBJECTIVE: No studies have specifically considered paternal understanding
      of menstruation. This study aimed to establish the degree of understanding of
      fathers of adolescent girls with menstrual symptoms relative to mothers. DESIGN
      AND SETTING: This was a cross-sectional survey-based study. Adolescent patients
      attending an outpatient gynecology clinic for dysmenorrhea and/or heavy menstrual
      bleeding and their parents were invited to complete surveys. PARTICIPANTS: Sixty
      surveys were completed (24 of 40 daughters, 20 of 40 mothers, 16 of 40 fathers).
      INTERVENTIONS AND MAIN OUTCOME MEASURES: Surveys aimed to test parents'
      understanding of menstrual symptoms and potential medications, as well as
      fathers' concerns with their daughters' health. RESULTS: The fathers' knowledge
      of menstrual symptoms was poorer than mothers, although most knew heavy menstrual
      bleeding (15/16, 94%) and mood swings (14/16, 87%). Many parents answered "don't
      know" or did not answer questions about potential consequences of medications,
      although parents were clearly concerned about side effects. Most fathers (13/16,
      81%) were open to discussing menstrual concerns with daughters; however, only 54%
      (13/24) of daughters were open to such discussions. Of fathers, 81% (13/16) were
      sympathetic/concerned, 56% (9/16) felt helpless, and 13% (2/16) were frustrated
      when daughters were in pain. When asked about effects, 88% (14/16) of fathers
      (79% [15/20] of mothers) were worried about their daughter's welfare and 63%
      (10/16) (55% [11/20] of mothers) about schooling. CONCLUSION: We present, to our
      knowledge, the first insight into fathers' knowledge of their daughters'
      menstrual health. Overall, parents have an incomplete picture of menstrual
      symptoms. Even in this cohort, which could be expected to be well informed
      because of their daughters' attendance at a tertiary hospital, it is clear that
      further knowledge would assist them caring for their daughters.

PMID- 29655582
TI  - Comparison of 3 image-guided adaptive strategies for bladder locoregional
      radiotherapy.
AB  - The objective of this study was to compare the dosimetric differences of a
      population-based planning target volume (PTV) approach and 3 proposed adaptive
      strategies: plan of the day (POD), patient-specific PTV (PS-PTV), and daily
      reoptimization (ReOpt). Bladder patients (n = 10) were planned and treated to 46
      Gy in 23 fractions with a full bladder in supine position by the standard
      strategy using a population-based PTV. For each patient, the adaptive strategy
      was executed retrospectively as follows: (1) POD-multiple distributions of
      various PTV sizes were generated, and the appropriate distribution based on the
      bladder of the day was selected for each fraction; (2) PS-PTV-population-based
      PTV was used for the first 5 fractions and a new PTV derived using information
      from these fractions was used to deliver the remaining 18 fractions; and (3)
      ReOpt-distribution was reoptimized for each fraction based on the bladder of the
      day. Daily dose was computed on all cone beam computed tomographies (CBCTs) and
      deformed back to the planning computed tomography (CT) for dose summation
      afterward. V95_Accu, the volume receiving an accumulated delivered dose of 43.7
      Gy (95% prescription dose), was measured for comparison. Mean V95_Accu (cm3)
      values were 1410 (standard deviation [SD]: 227), 1212 (SD: 186), 1236 (SD: 199),
      and 1101 (SD: 180) for standard, POD, PS-PTV, and ReOpt, respectively. All
      adaptive strategies significantly reduced the irradiated volume, with ReOpt
      demonstrating the greatest reduction compared with the standard (- 25%), followed
      by PS-PTV (- 16%) and POD (- 12%). The difference in the magnitude of reduction
      between ReOpt and the other 2 strategies reached statistical significance (p =
      0.0006). ReOpt is the best adaptive strategy at reducing the irradiated volume
      because of its frequent adaptation based on the daily geometry of the bladder.
      The need to adapt only once renders PS-PTV to be the best alternative adaptive
      strategy.

PMID- 29655583
TI  - The real world.

PMID- 29655584
TI  - Nanoemulsion adjuvant-driven redirection of TH2 immunity inhibits allergic
      reactions in murine models of peanut allergy.
AB  - BACKGROUND: Immunotherapy for food allergies involves progressive increased
      exposures to food that result in desensitization to food allergens in some
      subjects but not tolerance to the food. Therefore new approaches to suppress
      allergic immunity to food are necessary. Previously, we demonstrated that
      intranasal immunization with a nanoemulsion (NE) adjuvant induces robust mucosal
      antibody and TH17-polarized immunity, as well as systemic TH1-biased cellular
      immunity with suppression of pre-existing TH2-biased immunity. OBJECTIVE: We
      hypothesized that immunization with food in conjunction with the nanoemulsion
      adjuvant could lead to modulation of allergic reactions in food allergy by
      altering pre-existing allergic immunity and enhancing mucosal immunity. METHODS:
      Mice were sensitized to peanut with aluminum hydroxide or cholera toxin. The
      animals were then administered 3 monthly intranasal immunizations with peanut in
      the nanoemulsion adjuvant or saline. Mice were then challenged with peanut to
      examine allergen reactivity. RESULTS: The NE intranasal immunizations resulted in
      marked decreases in TH2 cytokine, IgG1, and IgE levels, whereas TH1 and mucosal
      TH17 immune responses were increased. After allergen challenge, these mice showed
      significant reductions in allergic hypersensitivity. Additionally, the NE
      immunizations significantly increased antigen-specific IL-10 production and
      regulatory T-cell counts, and the protection induced by NE was dependent in part
      on IL-10. Control animals immunized with intranasal peanut in saline had no
      modulation of their allergic response. CONCLUSIONS: NE adjuvant-mediated
      induction of mucosal TH17 and systemic TH1-biased immunity can suppress TH2
      mediated allergy through multiple mechanisms and protect against anaphylaxis.
      These results suggest the potential therapeutic utility of this approach in the
      setting of food allergy.

PMID- 29655585
TI  - Reply.

PMID- 29655586
TI  - Non-motor outcomes of subthalamic stimulation in Parkinson's disease depend on
      location of active contacts.
AB  - BACKGROUND: Subthalamic nucleus (STN) deep brain stimulation (DBS) improves
      quality of life (QoL), motor, and non-motor symptoms (NMS) in Parkinson's disease
      (PD). Few studies have investigated the influence of the location of
      neurostimulation on NMS. OBJECTIVE: To investigate the impact of active contact
      location on NMS in STN-DBS in PD. METHODS: In this prospective, open-label,
      multicenter study including 50 PD patients undergoing bilateral STN-DBS, we
      collected NMSScale (NMSS), NMSQuestionnaire (NMSQ), Hospital Anxiety and
      Depression Scale (anxiety/depression, HADS-A/-D), PDQuestionnaire-8 (PDQ-8),
      Scales for Outcomes in PD-motor examination, motor complications, activities of
      daily living (ADL), and levodopa equivalent daily dose (LEDD) preoperatively and
      at 6 months follow-up. Changes were analyzed with Wilcoxon signed-rank/t-test and
      Bonferroni-correction for multiple comparisons. Although the STN was targeted
      visually, we employed an atlas-based approach to explore the relationship between
      active contact locations and DBS outcomes. Based on fused MRI/CT-images, we
      identified Cartesian coordinates of active contacts with patient-specific Mai
      atlas standardization. We computed linear mixed-effects models with x-/y-/z
      coordinates as independent, hemispheres as within-subject, and test change scores
      as dependent variables. RESULTS: NMSS, NMSQ, PDQ-8, motor examination,
      complications, and LEDD significantly improved at follow-up. Linear mixed-effect
      models showed that NMS and QoL improvement significantly depended on more medial
      (HADS-D, NMSS), anterior (HADS-D, NMSQ, PDQ-8), and ventral (HADS-A/-D, NMSS, PDQ
      8) neurostimulation. ADL improved more in posterior, LEDD in lateral
      neurostimulation locations. No relationship was observed for motor examination
      and complications scores. CONCLUSIONS: Our study provides evidence that more
      anterior, medial, and ventral STN-DBS is significantly related to more beneficial
      non-motor outcomes.

PMID- 29655587
TI  - Short-term quality of life after subthalamic stimulation depends on non-motor
      symptoms in Parkinson's disease.
AB  - BACKGROUND: Subthalamic nucleus (STN) deep brain stimulation (DBS) improves
      quality of life (QoL), motor, and non-motor symptoms (NMS) in advanced
      Parkinson's disease (PD). However, considerable inter-individual variability has
      been observed for QoL outcome. HYPOTHESIS: We hypothesized that demographic and
      preoperative NMS characteristics can predict postoperative QoL outcome. METHODS:
      In this ongoing, prospective, multicenter study (Cologne, Manchester, London)
      including 88 patients, we collected the following scales preoperatively and on
      follow-up 6 months postoperatively: PDQuestionnaire-8 (PDQ-8), NMSScale (NMSS),
      NMSQuestionnaire (NMSQ), Scales for Outcomes in PD (SCOPA)-motor examination, 
      complications, and -activities of daily living, levodopa equivalent daily dose.
      We dichotomized patients into "QoL responders"/"non-responders" and screened for
      factors associated with QoL improvement with (1) Spearman-correlations between
      baseline test scores and QoL improvement, (2) step-wise linear regressions with
      baseline test scores as independent and QoL improvement as dependent variables,
      (3) logistic regressions using aforementioned "responders/non-responders" as
      dependent variable. RESULTS: All outcomes improved significantly on follow-up.
      However, approximately 44% of patients were categorized as "QoL non-responders".
      Spearman-correlations, linear and logistic regression analyses were significant
      for NMSS and NMSQ but not for SCOPA-motor examination. Post-hoc, we identified
      specific NMS (flat moods, difficulties experiencing pleasure, pain, bladder
      voiding) as significant contributors to QoL outcome. CONCLUSIONS: Our results
      provide evidence that QoL improvement after STN-DBS depends on preoperative NMS
      characteristics. These findings are important in the advising and selection of
      individuals for DBS therapy. Future studies investigating motor and non-motor PD
      clusters may enable stratifying QoL outcomes and help predict patients'
      individual prospects of benefiting from DBS.

PMID- 29655588
TI  - Resident and monocyte-derived Langerhans cells are required for imiquimod-induced
      psoriasis-like dermatitis model.
AB  - BACKGROUND: Langerhans cells (LCs) are dendritic cells that reside in the
      epidermis and local inflammation results in an increased differentiation of
      monocyte-derived LCs. Only few studies have investigated on the role of LCs in
      psoriasis-like dermatitis model, but the results are variable and the exact role
      of LCs in psoriasis model remains to be elucidated. OBJECTIVE: To explore the
      functional role of resident (rLCs) and monocyte-derived LCs (mLCs) in imiquimod
      (IMQ)-induced psoriasis-like inflammation using human Langerin-diphtheria toxin
      subunit A (huLang-DTA) mice. METHODS: 5% IMQ cream was topically applied on the
      skins. Clinical and histopathological features were evaluated. Psoriasis-related
      gene expression was analyzed by quantitative polymerase chain reaction. The
      production of psoriasis-related cytokines including IL-17A and IL-22 by T cells
      were assessed by flow cytometry from the lesional skins. RESULTS: huLang-DTA mice
      showed a common depletion of both rLCs and mLCs in the IMQ-treated skins. huLang
      DTA mice had a reduced IMQ-induced psoriasis-like inflammation featuring
      erythema, scale, and thickness compared with wild-type mice. Psoriatic lesions
      from huLang-DTA mice had a decreased level of Il23a and accordingly demonstrated
      an attenuated cytokine production of IL-17A and IL-22 from gammadeltalow T cells.
      mLCs revealed a significantly greater level of IL-23 expression compared to rLCs
      in response to topical IMQ treatment. CONCLUSION: Although both rLCs and mLCs are
      involved in the development of IMQ-induced psoriasis-like dermatitis,
      inflammation-induced mLCs present a superior capacity for producing IL-23 in this
      murine experimental model of psoriasis.

PMID- 29655589
TI  - Emerging applications of eye-tracking technology in dermatology.
AB  - Eye-tracking technology has been used within a multitude of disciplines to
      provide data linking eye movements to visual processing of various stimuli (i.e.,
      x-rays, situational positioning, printed information, and warnings). Despite the
      benefits provided by eye-tracking in allowing for the identification and
      quantification of visual attention, the discipline of dermatology has yet to see
      broad application of the technology. Notwithstanding dermatologists' heavy
      reliance upon visual patterns and cues to discriminate between benign and
      atypical nevi, literature that applies eye-tracking to the study of dermatology
      is sparse; and literature specific to patient-initiated behaviors, such as skin
      self-examination (SSE), is largely non-existent. The current article provides a
      review of eye-tracking research in various medical fields, culminating in a
      discussion of current applications and advantages of eye-tracking for dermatology
      research.

PMID- 29655590
TI  - Early initiation of extracorporeal photochemotherapy increases response for
      chronic graft versus host disease following steroid failure.
AB  - OBJECTIVES: Chronic graft versus host disease (GVHD) is one of the major
      obstacles to achieve success in allogeneic hematopoietic stem cell
      transplantation (allo-HSCT). Extracorporeal photochemotherapy (ECP) has been
      demonstrated to be an effective modality for the treatment of GVHD in previous
      studies but they vary in terms of initiation and duration. Our aim is to
      demonstrate the characteristics of our patients who received ECP for chronic GVHD
      to clarify the best treatment scheme. MATERIAL AND METHODS: In this study, we
      retrospectively evaluated 34 patients with steroid refractory chronic GVHD (n=34)
      who were treated with ECP between 2001 and 2015. The initiation of ECP was
      determined according to patient status and the physician's preference. RESULTS:
      ECP was initiated early (<=3months) as the preferred second-line treatment after
      failure of methylprednisolone treatment in 12 patients (35%), 22 steroid
      refractory patients (65%) received ECP later. In all cohorts, 10 (29%) and 14
      (41%) of 34 patients achieved complete response (CR) and partial response (PR),
      respectively, with an overall response rate (ORR) of 70. Early initiation of ECP
      after chronic GVHD diagnosis (<=3months vs more than 3months) was associated with
      increased rates of response (92% vs 59%, P=0.046) in which the severity of
      diseases were similar. Patients with skin involvement in early treatment group
      had statistically better response. Mild side effects were detected in only 6
      patients (16%). CONCLUSION: ECP is a safe treatment modality and particularly
      effective when initiated soon after steroid failure in chronic GVHD.

PMID- 29655591
TI  - Open reduction and internal fixation in a one-stage anterior cruciate ligament
      reconstruction surgery for the treatment of tibial plateau fractures: A case
      report and literature review.
AB  - Treatment of tibial plateau fractures associated with anterior cruciate ligament
      (ACL) injuries can be challenging. Maintaining the joint surface and axis are two
      main principles for the management of patients with tibial plateau fractures.
      Herein, we describe a patient with tibial plateau fracture of Schatzker type VI
      associated with complete ACL rupture. Although in a two-stage reconstruction
      surgery for treatment of its rupture seem to be accepted by most orthopaedic
      surgeons in cases of ACL injuries, we treated our patient with ORIF in a one
      stage ACL reconstruction surgery. At the 1-year follow-up, the patient gained
      full range of motion and was functioning well. We reviewed the literature on
      performing ORIF in a one-stage ACL reconstruction for the treatment of tibial
      plateau fractures, which seemed to be a reasonable management approach that
      supported its use for the treatment of this patient.

PMID- 29655592
TI  - Development of a blunt chest injury care bundle: An integrative review.
AB  - BACKGROUND: Blunt chest injuries (BCI) are associated with high rates of
      morbidity and mortality. There are many interventions for BCI which may be able
      to be combined as a care bundle for improved and more consistent outcomes.
      OBJECTIVE: To review and integrate the BCI management interventions to inform the
      development of a BCI care bundle. METHODS: A structured search of the literature
      was conducted to identify studies evaluating interventions for patients with BCI.
      Databases MEDLINE, CINAHL, PubMed and Scopus were searched from 1990-April 2017.
      A two-step data extraction process was conducted using pre-defined data fields,
      including research quality indicators. Each study was appraised using a quality
      assessment tool, scored for level of evidence, then data collated into
      categories. Interventions were also assessed using the APEASE criteria then
      integrated to develop a BCI care bundle. RESULTS: Eighty-one articles were
      included in the final analysis. Interventions that improved BCI outcomes were
      grouped into three categories; respiratory intervention, analgesia and surgical
      intervention. Respiratory interventions included continuous positive airway
      pressure and high flow nasal oxygen. Analgesia interventions included regular
      multi-modal analgesia and paravertebral or epidural analgesia. Surgical fixation
      was supported for use in moderate to severe rib fractures/BCI. Interventions
      supported by evidence and that met APEASE criteria were combined into a BCI care
      bundle with four components: respiratory adjuncts, analgesia, complication
      prevention, and surgical fixation. CONCLUSIONS: The key components of a BCI care
      bundle are respiratory support, analgesia, complication prevention including
      chest physiotherapy and surgical fixation.

PMID- 29655593
TI  - Investigating the potential of an autodissemination system for managing
      populations of vine weevil, Otiorhynchus sulcatus (Coleoptera: Curculionidae)
      with entomopathogenic fungi.
AB  - Vine weevil, also known as black vine weevil, (Otiorhynchus sulcatus) is an
      economically important pest affecting soft fruit and nursery stock in temperate
      regions. We used laboratory and polytunnel experiments to investigate a novel
      control system based on autodissemination of spores of an entomopathogenic fungus
      to populations of adult vine weevils. The fungus was applied as a conidial
      powder, used on its own or formulated with talc, to a simple plastic refuge for
      vine weevils. The potential for adult weevils to disseminate the fungus was
      investigated first in polytunnel experiments using fluorescent powders applied to
      the refuge in lieu of fungal conidia. In this system, 88% of adult weevils came
      in contact with the powder within 48 h. When the powder was applied to five adult
      weevils that were then placed within a population of 35 potential recipients, it
      was transmitted on average to 75% of the recipient population within 7 days.
      Three isolates of entomopathogenic fungi (Beauveria bassiana isolate codes 433.99
      and 1749.11 and Metarhizium brunneum isolate code 275.86), selected from a
      laboratory virulence screen. These three isolates were then investigated for
      efficacy when applied as conidial powders in artificial refuges placed among
      populations of adult weevils held in experimental boxes in the laboratory at 20 
      degrees C. Under this regime, the fungal isolates caused 70-90% mortality of
      adult weevils over 28 days. A final polytunnel experiment tested the efficacy of
      conidial powders of M. brunneum 275.86 placed in artificial refuges to increase
      vine weevil mortality. Overall weevil mortality was relatively low (26-41%) but
      was significantly higher in cages in which the conidial powders were placed in
      refuge traps than in cages with control traps. The lower weevil mortality
      recorded in the polytunnel experiment compared to the laboratory test was most
      likely a consequence of the greater amounts of inoculum required to kill adult
      weevils when conditions fluctuate between favourable and unfavourable
      temperatures e.g. below 15  degrees C. The potential of an autodissemination
      system for entomopathogenic fungi as a means of controlling vine weevil as part
      of an integrated pest management programme is discussed.

PMID- 29655594
TI  - No effect of prenatal vitamin D deficiency on autism-relevant behaviours in
      multiple inbred strains of mice.
AB  - Autism Spectrum Disorders (ASD) is a group of neurodevelopmental disorders
      commonly characterised by verbal and non-verbal communication deficits, impaired
      social interaction and repetitive, stereotypic behaviours. The aetiology of ASD
      is most likely a combination of genetic and environmental factors.
      Epidemiological evidence suggests that prenatal vitamin D deficiency is
      associated with an increased incidence of ASD. The overall aim of this study was
      to investigate prenatal vitamin D deficiency on ASD-related behavioural
      phenotypes in multiple inbred strains of mice. We included two commonly used
      inbred mouse strains (C57BL/6J and BALB/c) as well as inbred BTBR mice, which
      show ASD-related behaviours, such as excessive self-grooming, hyperlocomotion,
      social interaction deficits and altered communication. We also studied the effect
      of prenatal vitamin D deficiency in a fourth strain; an F1 cross of C57BL/6J x
      BTBR mice, which have a partial BTBR phenotype. To implement prenatal vitamin D
      deficiency, female mice were placed on vitamin D deplete diets for ten weeks,
      including mating and gestation, until littering, when all dams were switched to
      the control diet. Behavioural symptoms related to ASD were measured, including
      isolation-induced ultrasonic vocalisations to measure communication, the three
      chambered social interaction task to observe social interaction, the open field
      test to examine hyperlocomotion, assessment of grooming and rearing behaviour and
      finally the active place avoidance task to observe spatial learning and memory in
      response to a mild foot shock. Prenatal vitamin D deficiency had a negative
      impact on preference for social novelty in C57BL/6J mice, despite similar
      vocalisation phenotypes, and prenatal vitamin D-deficient F1 mice were found to
      be hypolocomotive in the open field test yet performed better on the active place
      avoidance task. Despite clear differences between strains, there were no other
      consistent significant main effects of maternal diet on the behaviour of the
      offspring. Vitamin D deficiency has been implicated as a risk factor for ASD and
      these data show that there is greater variation between different inbred strains
      in ASD-related behaviour, suggesting that prenatal vitamin D deficiency is not
      sufficient to recapitulate an ASD phenotype in multiple inbred strains of mice.

PMID- 29655595
TI  - Working memory training in congenitally blind individuals results in an
      integration of occipital cortex in functional networks.
AB  - The functional relevance of crossmodal activation (e.g. auditory activation of
      occipital brain regions) in congenitally blind individuals is still not fully
      understood. The present study tested whether the occipital cortex of blind
      individuals is integrated into a challenged functional network. A working memory
      (WM) training over four sessions was implemented. Congenitally blind and matched
      sighted participants were adaptively trained with an n-back task employing either
      voices (auditory training) or tactile stimuli (tactile training). In addition, a
      minimally demanding 1-back task served as an active control condition. Power and
      functional connectivity of EEG activity evolving during the maintenance period of
      an auditory 2-back task were analyzed, run prior to and after the WM training.
      Modality-specific (following auditory training) and modality-independent WM
      training effects (following both auditory and tactile training) were assessed.
      Improvements in auditory WM were observed in all groups, and blind and sighted
      individuals did not differ in training gains. Auditory and tactile training of
      sighted participants led, relative to the active control group, to an increase in
      fronto-parietal theta-band power, suggesting a training-induced strengthening of
      the existing modality-independent WM network. No power effects were observed in
      the blind. Rather, after auditory training the blind showed a decrease in theta
      band connectivity between central, parietal, and occipital electrodes compared to
      the blind tactile training and active control groups. Furthermore, in the blind
      auditory training increased beta-band connectivity between fronto-parietal,
      central and occipital electrodes. In the congenitally blind, these findings
      suggest a stronger integration of occipital areas into the auditory WM network.

PMID- 29655596
TI  - Validation of the nursing workload scoring systems "Nursing Activities Score"
      (NAS), and "Therapeutic Intervention Scoring System for Critically Ill Children"
      (TISS-C) in a Greek Paediatric Intensive Care Unit.
AB  - OBJECTIVES: To assess the reliability and validity of the Greek version of
      Nursing Activities Score (NAS), and Therapeutic Intervention Scoring System for
      Critically Ill Children (TISS-C) in a Greek Paediatric Intensive Care Unit
      (PICU). RESEARCH METHODOLOGY: A methodological study was performed in one PICU of
      the largest Paediatric Hospital in Athens-Greece. The culturally adapted and
      validated Greek NAS version, enriched according to the Norwegian paediatric one
      (P-NAS), was used. TISS-C and Norwegian paediatric interventions were translated
      to Greek language and backwards. Therapeutic Intervention Scoring System (TISS
      28) was used as a gold standard. Two independent observers simultaneously
      recorded 30 daily P-NAS and TISS-C records. Totally, 188 daily P-NAS, TISS-C and
      TISS-28 reports in a sample of 29 patients have been obtained during five weeks.
      Descriptive statistics, reliability and validity measures were applied using SPSS
      (ver 22.0) (p <= 0.05). RESULTS: Kappa was 0.963 for P-NAS and 0.9895 for TISS-C
      (p < 0.001) and Intraclass Correlation Coefficient for all scale items of TISS-C
      was 1.00 (p < 0.001). P-NAS, TISS-28 and TISS-C measurements were significantly
      correlated (0.680 <= rho <= 0.743, p < 0.001). The mean score(+/-SD) for TISS-28,
      P-NAS and TISS-C was 23.05(+/-5.72), 58.14(+/-13.98) and 20.21(+/-9.66)
      respectively. CONCLUSION: These results support the validity of P-NAS and TISS-C
      scales to be used in greek PICUs.

PMID- 29655597
TI  - Affective spectrum symptoms and self-criticism: A behavioral genetic approach.

PMID- 29655598
TI  - Individual differences in the energizing effects of caffeine on effort-based
      decision-making tests in rats.
AB  - Motivated behavior is characterized by activation and high work output. Nucleus
      accumbens (Nacb) modulates behavioral activation and effort-based decision
      making. Caffeine is widely consumed because of its energizing properties. This
      methylxanthine is a non-selective adenosine A1/A2A receptor antagonist. Adenosine
      receptors are highly concentrated in Nacb. Adenosine agonists injected into Nacb,
      shift preference towards low effort alternatives. The present studies
      characterized effort-related effects of caffeine in a concurrent progressive
      ratio (PROG)/free reinforcer choice procedure that requires high levels of work
      output, and generates great variability among different animals. Male Sprague
      Dawley rats received an acute dose of caffeine (2.5-20.0 mg/kg, IP) and 30 min
      later were tested in operant boxes. One group was food-restricted and had to
      lever pressed for high carbohydrate pellets, another group was non-food
      restricted and lever pressed for a high sucrose solution. Caffeine (2.5 and 5.0
      mg/kg) increased lever pressing in food-restricted animals that were already high
      responders. However, in non-restricted animals, caffeine (5.0 and 10.0 mg/kg)
      increased work output only among low responders. In fact, caffeine (10.0 and 20.0
      mg/kg) in non-restricted animals, reduced lever pressing among high responders in
      the PROG task, and also in a different group of animals lever pressing in an easy
      task (fixed ratio 7 schedule) that uniformly generates high levels of responding.
      Caffeine did not modify sucrose preference or consumption under free access
      conditions. Thus, when animals do not have a homeostatic need, caffeine can help
      those not very intrinsically motivated to work harder for a more palatable
      reward. However, caffeine can disrupt performance of animals intrinsically
      motivated to work hard for a better reward.

PMID- 29655599
TI  - Plasma from some cancer patients inhibits adenoviral Ad5f35 vector transduction
      of dendritic cells.
AB  - BACKGROUND: Pooled AB serum is often used as a media supplement for cell culture
      but it has the potential to transmit infectious diseases. To avoid this risk, we
      used autologous plasma as a media supplement for manufacturing dendritic cells
      (DCs) for cancer immunotherapy. We noticed inconsistencies in the DCs and
      investigated their nature and cause. METHODS: Adenovirus human epidural growth
      factor receptor 2 (adHER2/neu) DCs for 21 patients were manufactured from
      autologous peripheral blood monocytes that were treated with granulocyte
      macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4 for 3 days,
      transduced with Ad5f35HER2ECTM and then treated with lipopolysaccharide and
      interferon (IFN)-gamma for 1 day. The cells were cultured in RPMI-1640
      supplemented with either 10% heat inactivated autologous or AB plasma. RESULTS:
      Twenty-eight adHER2/neu DCs were manufactured for 21 patients using autologous
      plasma and 68 were manufactured for 20 of those patients using AB plasma. The
      expression of human epidural growth factor receptor 2 (HER2/neu) was less for DCs
      manufactured with autologous plasma (70.3 +/- 33.3% versus 86.1 +/- 22.8%; P
      <0.01). Manufacturing adHER2/neu DCs using monocytes from three healthy subjects
      and plasma from one patient with low HER2/neu expression (18%) resulted in low
      HER2/neu expression by all three DCs (13%, 16% and 23%). Analysis of the levels
      of 1322 proteins in eight plasma samples associated with low HER2/neu expression
      and in 12 associated with high HER2/neu expression revealed that the levels of 14
      predicted HER2/neu transduction efficiency. CONCLUSION: The manufacture of
      adHER2/neu DC using autologous plasma as a media supplement resulted in
      inconsistent HER2/neu expression. It is likely that variability in the levels of
      multiple proteins in autologous plasma contributed to low HER2/neu expression.

PMID- 29655600
TI  - Response of epilithic diatom communities to environmental gradients along an
      Ecuadorian Andean River.
AB  - Epilithic diatom communities are particularly suitable for the evaluation of
      freshwater quality. In Ecuador, however, no water quality index includes this
      biotic parameter. This work is the first attempt in the country to determine the
      composition of epilithic diatom communities associated with different degrees of
      eutrophication. This was accomplished by measuring physical, chemical and
      microbiological variables at five sampling sites along the Pita River, Ecuador,
      from August to December 2016. The results indicate a clear gradient of
      eutrophication from sampling sites P1 (good water) in the upper reaches to P5
      (bad water) located in the lower reaches. Concerning diatom analyses, the results
      indicated a high diversity for tropical areas in terms of species richness,
      varying from S=34 in headwaters to S=42 downstream. Moreover, the results
      obtained suggest a lack of concordance with the trophic values given to some of
      the epilithic diatoms in the literature. There were also species that seem to be
      sensitive to downstream nutrient increases that were not considered as
      bioindicators in previous studies. We concluded that the trophic values of diatom
      species available in the scientific literature are not directly applicable to
      their sites in the Pita River. Hence, it is necessary to establish a trophic
      diatom index for the Andean region of Ecuador.

PMID- 29655601
TI  - Placental disposition of the immunosuppressive drug tacrolimus in renal
      transplant recipients and in ex vivo perfused placental tissue.
AB  - Currently, tacrolimus is the most potent immunosuppressive agent for renal
      transplant recipients and is commonly prescribed during pregnancy. As data on
      placental exposure and transfer are limited, we studied tacrolimus placental
      handling in samples obtained from renal transplant recipients. We found transfer
      to venous umbilical cord blood, but particularly noted a strong placental
      accumulation. In patient samples, tissue concentrations in a range of 55-82 ng/g
      were found. More detailed ex vivo dual-side perfusions of term placentas from
      healthy women revealed a tissue-to-maternal perfusate concentration ratio of 113
      +/- 49 (mean +/- SEM), underlining the placental accumulation found in vivo.
      During the 3 h ex vivo perfusion interval no placental transfer to the fetal
      circulation was observed. In addition, we found a non-homogeneous distribution of
      tacrolimus across the perfused cotyledons. In conclusion, we observed extensive
      accumulation of tacrolimus in placental tissue. This warrants further studies
      into potential effects on placental function and immune cells of the placenta.

PMID- 29655602
TI  - Overexpression of CTRP3 protects against sepsis-induced myocardial dysfunction in
      mice.
AB  - C1q/tumor necrosis factor-related protein-3 (CTRP3) shows striking homologies of
      genomic structure to the adiponectin. In this study, we aimed to investigate the
      protective role of CTRP3 against sepsis-induced cardiomyopathy. Here, we
      overexpressed CTRP3 in myocardium by direct intramyocardial injection and
      constructed a model of lipopolysaccharide (LPS)-induced sepsis in mice. Our
      results demonstrated that cardiac-specific overexpression of CTRP3 remarkably
      attenuated myocardial dysfunction and increased the phosphorylation level of
      AMPKalpha during LPS-induced sepsis. The anti-inflammatory effects of CTRP3, as
      determined by decreased mRNA levels of TNF-alpha, IL-6 and a lower protein
      expression of phosphorylated NF-kappaB p65 and IkappaBalpha, was detected in mice
      following LPS treatment. Additionally, CTRP3 suppressed cardiac apoptosis induced
      by LPS in mice as indicated by terminal deoxynucleotidyl transferase nick-end
      labeling (TUNEL) staining and western blot for Cleaved-caspase3, Bax and Bcl-2.
      In conclusion, CTRP3 could protect against sepsis-induced myocardial dysfunction
      in mice. The cardioprotective effects of CTRP3 might be mediated by activating
      AMPKalpha signaling pathway and blunting inflammatory response and apoptosis.

PMID- 29655603
TI  - New technologies to uncover the molecular basis of disorders of sex development.
AB  - The elegant developmental biology experiments conducted in the 1940s by French
      physiologist Alfred Jost demonstrated that the sexual phenotype of a mammalian
      embryo depended whether the embryonic gonad develops into a testis or not. In
      humans, anomalies in the processes that regulate development of chromosomal,
      gonadal or anatomic sex result in a spectrum of conditions termed
      Disorders/Differences of Sex Development (DSD). Each of these conditions is rare,
      and understanding of their genetic etiology is still incomplete. Historically,
      DSD diagnoses have been difficult to establish due to the lack of standardization
      of anatomical and endocrine phenotyping procedures as well as genetic testing.
      Yet, a definitive diagnosis is critical for optimal management of the medical and
      psychosocial challenges associated with DSD conditions. The advent in the
      clinical realm of next-generation sequencing methods, with constantly decreasing
      price and turnaround time, has revolutionized the diagnostic process. Here we
      review the successes and limitations of the genetic methods currently available
      for DSD diagnosis, including Sanger sequencing, karyotyping, exome sequencing and
      chromosomal microarrays. While exome sequencing provides higher diagnostic rates,
      many patients still remain undiagnosed. Newer approaches, such as whole-genome
      sequencing and whole-genome mapping, along with gene expression studies, have the
      potential to identify novel DSD-causing genes and significantly increase total
      diagnostic yield, hopefully shortening the patient's journey to an accurate
      diagnosis and enhancing health-related quality-of-life outcomes for patients and
      families.

PMID- 29655604
TI  - Coating with Microbial Hydrophobins: A Novel Approach to Develop Smart Drug
      Nanoparticles.
AB  - Microbial hydrophobin (MH)-based surface coating is emerging as a novel protein
      engineering approach for drug nanoparticles to enhance the solubility and
      stability of therapeutic agents. These hydrophobins are amphiphilic proteins that
      can form self-assembled monolayers on hydrophobic materials and can coat
      nanoparticles for efficient drug delivery.

PMID- 29655605
TI  - Physiology and pathophysiology of renal erythropoietin-producing cells.
AB  - Anemia is a common complication and contributes to increased morbidity and
      mortality in chronic kidney disease (CKD) patients. Whereas there has been a
      significant improvement of understanding the underlying mechanism of
      erythropoiesis, the treatment of renal anemia is still restricted to
      erythropoietin (EPO)-stimulating agents. The purpose of this article is to review
      the physiology of erythropoiesis, functional role of EPO and underlying molecular
      and cellular basis that regulate EPO production. Regulation of EPO production is
      at mRNA level. When anemia or hypoxia occurs, transcriptional factor, hypoxia
      inducible factor (HIF), binds to EPO 5' hypoxic response element and EPO gene
      transcription increases. The renal EPO is mainly produced by pericytes. In CKD,
      pericytes transdifferentiate to myofibroblasts, and subsequently the ability of
      EPO production decreases, leading to renal anemia. Recent experimental and
      clinical studies show the promising efficacy of prolyl hydroxylase inhibitors in
      renal anemia through increasing EPO production by stabilizing HIF. Recent
      advances on epigenetics create a new field to study EPO gene expression at
      chromatin level. We will discuss the role of demethylating agent on restoring EPO
      expression, providing a novel approach to the treatment of renal anemia.

PMID- 29655606
TI  - The prevalence and bother of lower urinary tract symptoms in men and women aged
      40 years or over in Taiwan.
AB  - BACKGROUND/PURPOSE: The prevalence of lower urinary tract symptoms (LUTS) in men
      and women in the general population in Taiwan is unclear. Community-based data on
      the epidemiology and effects of LUTS would therefore help improve understanding
      of the condition in this country. METHODS: This study was an internet-based, self
      administered survey, conducted in randomly selected adults aged >=40 years.
      Participants answered questions on International Continence Society (ICS) symptom
      definitions, the International Prostate Symptom Score (IPSS) and the overactive
      bladder (OAB) symptom score. RESULTS: The study population comprised 2068 adults
      (51.4% women) with a mean age of 55 years. Using criteria from the ICS, LUTS were
      present in 60% of men and 57% of women. The prevalence of LUTS increased with age
      in both men and women. The most bothersome symptoms were terminal dribble,
      incomplete emptying and nocturia in men, and nocturia, perceived frequency and
      urgency in women. In the overall population, according to IPSS, 30% had at least
      moderate symptoms. OAB prevalence was 16% in both men and women. The likelihood
      of consulting a healthcare professional about urinary symptoms was low and not
      significantly different between men and women with LUTS (17% and 14%,
      respectively). CONCLUSION: More than half of men and women aged >=40 years in
      Taiwan are affected by LUTS, and these symptoms are often bothersome. However,
      few individuals with LUTS consult healthcare professionals about their symptoms.
      Improved diagnosis and treatment of LUTS in Taiwan are needed to reduce the
      deleterious effects of the condition. CLINICALTRIALS. GOV IDENTIFIER:
      NCT02618421.

PMID- 29655607
TI  - Stressful Events as Teaching Signals for the Brain.
AB  - Stressful events are better remembered than mundane events. We explain this
      advantage by reconceptualizing stress in terms of cumulative prediction errors
      (PEs) that promote rapid learning of events. This proposal integrates the effects
      of stress on perception and memory, and provides exciting new perspectives for
      research on stress and cognition.

PMID- 29655608
TI  - Rational design of pyridyl derivatives of vanillin for the treatment of sickle
      cell disease.
AB  - Hypoxia-induced polymerization of sickle hemoglobin (Hb S) is the principal
      phenomenon that underlays the pathophysiology and morbidity associated with
      sickle cell disease (SCD). Opportunely, as an allosteric protein, hemoglobin (Hb)
      serves as a convenient and potentially critical druggable target. Consequently,
      molecules that prevent Hb S polymerization (Hb modifiers), and the associated
      erythrocyte sickling have been investigated-and retain significant interest-as a
      viable therapeutic strategy for SCD. This group of molecules, including aromatic
      aldehydes, form high oxygen affinity Schiff-base adducts with Hb S, which are
      resistant to polymerization. Here, we report the design and synthesis of novel
      potent antisickling agents (SAJ-009, SAJ-310 and SAJ-270) based on the
      pharmacophore of vanillin and INN-312, a previously reported pyridyl derivative
      of vanillin. These novel derivatives exhibited superior in vitro binding and
      pharmacokinetic properties compared to vanillin, which translated into
      significantly enhanced allosteric and antisickling properties. Crystal structure
      studies of liganded Hb in the R2 quaternary state in complex with SAJ-310
      provided important insights into the allosteric and antisickling properties of
      this group of compounds. While these derivatives generally show similar in vitro
      biological potency, significant structure-dependent differences in their
      biochemical profiles would help predict the most promising candidates for
      successful in vivo pre-clinical translational studies and inform further
      structural modifications to improve on their pharmacologic properties.

PMID- 29655609
TI  - Structure activity relationship studies on rhodanines and derived enethiol
      inhibitors of metallo-beta-lactamases.
AB  - Metallo-beta-lactamases (MBLs) enable bacterial resistance to almost all classes
      of beta-lactam antibiotics. We report studies on enethiol containing MBL
      inhibitors, which were prepared by rhodanine hydrolysis. The enethiols inhibit
      MBLs from different subclasses. Crystallographic analyses reveal that the
      enethiol sulphur displaces the di-Zn(II) ion bridging 'hydrolytic' water. In
      some, but not all, cases biophysical analyses provide evidence that
      rhodanine/enethiol inhibition involves formation of a ternary MBL enethiol
      rhodanine complex. The results demonstrate how low molecular weight active site
      Zn(II) chelating compounds can inhibit a range of clinically relevant MBLs and
      provide additional evidence for the potential of rhodanines to be hydrolysed to
      potent inhibitors of MBL protein fold and, maybe, other metallo-enzymes, perhaps
      contributing to the complex biological effects of rhodanines. The results imply
      that any medicinal chemistry studies employing rhodanines (and related scaffolds)
      as inhibitors should as a matter of course include testing of their hydrolysis
      products.

PMID- 29655610
TI  - Structure based drug design and in vitro metabolism study: Discovery of N-(4
      methylthiophenyl)-N,2-dimethyl-cyclopenta[d]pyrimidine as a potent microtubule
      targeting agent.
AB  - We report a series of tubulin targeting agents, some of which demonstrate potent
      antiproliferative activities. These analogs were designed to optimize the
      antiproliferative activity of 1 by varying the heteroatom substituent at the 4'
      position, the basicity of the 4-position amino moiety, and conformational
      restriction. The potential metabolites of the active compounds were also
      synthesized. Some compounds demonstrated single digit nanomolar IC50 values for
      antiproliferative effects in MDA-MB-435 melanoma cells. Particularly, the S
      methyl analog 3 was more potent than 1 in MDA-MB-435 cells (IC50 = 4.6 nM).
      Incubation of 3 with human liver microsomes showed that the primary metabolite of
      the S-methyl moiety of 3 was the methyl sulfinyl group, as in analog 5. This
      metabolite was equipotent with the lead compound 1 in MDA-MB-435 cells (IC50 =
      7.9 nM). Molecular modeling and electrostatic surface area were determined to
      explain the activities of the analogs. Most of the potent compounds overcome
      multiple mechanisms of drug resistance and compound 3 emerged as the lead
      compound for further SAR and preclinical development.

PMID- 29655611
TI  - Development of a Ga-68 labeled PET tracer with short linker for prostate-specific
      membrane antigen (PSMA) targeting.
AB  - Glu-Urea-Lys (GUL) derivatives have been reported as prostate-specific membrane
      antigen (PSMA) agent. We developed derivatives of GUL conjugated with NOTA or
      DOTA via a thiourea linker and tested their feasibility as PSMA imaging agents
      after labeling with 68Ga. NOTA-GUL and DOTA-GUL were synthesized and labeled with
      68Ga using generator-eluted 68GaCl3 in 0.1 M HCl in the presence of 1 M NaOAc at
      pH 5.5. The stabilities of 68Ga-labeled compounds in human serum were tested at
      37.5  degrees C. A competitive binding assay was performed using the PSMA
      positive prostate cancer cell line 22Rv1 and [125I]MIP-1072 (PSMA-specific
      binding agent) as a tracer. Biodistribution and micro-PET studies were performed
      using 22Rv1-xenograft BALB/c nude mice. The radiolabeling efficiency of NOTA-GUL
      (>99%) was higher than that of DOTA-GUL (92%). The IC50 of Ga-NOTA-GUL was 18.3
      nM. In the biodistribution study, tumor uptake of 68Ga-NOTA-GUL (5.40% ID/g) was
      higher than that of 68Ga-DOTA-GUL (4.66% ID/g) at 1 h. Tumor/muscle and
      tumor/blood uptake ratios of 68Ga-NOTA-GUL (31.8 and 135, respectively) were
      significantly higher than those of 68Ga-DOTA-GUL (16.1 and 31.1, respectively).
      The tumor/kidney uptake ratio of 68Ga-NOTA-GUL was 3.4-fold higher than that of
      68Ga-DOTA-GUL. 68Ga-NOTA-GUL showed specific uptake to PSMA positive tumor
      xenograft and was blocked by co-injection of the cold ligand. In conclusion, we
      successfully synthesized 68Ga-NOTA-GUL and 68Ga-DOTA-GUL for prostate cancer
      imaging. 68Ga-NOTA-GUL showed better radiochemical and biodistribution results.
      68Ga-NOTA-GUL may be a promising PSMA targeting radiopharmaceutical.

PMID- 29655612
TI  - Practical application of ligand efficiency metrics in lead optimisation.
AB  - The use of composite metrics that normalise biological potency values in relation
      to markers of physicochemical properties, such as size or lipophilicity, has
      gained a significant amount of traction with many medicinal chemists in recent
      years. However, there is no consensus on best practice in the area and their
      application has attracted some criticism. Here we present our approach to their
      application in lead optimisation projects, provide an objective discussion of the
      principles we consider important and illustrate how our use of lipophilic ligand
      efficiency enabled the progression of a number of our successful drug discovery
      projects. We derive, from this and some recent literature highlights, a set of
      heuristic guidelines for lipophilicity based optimisation that we believe are
      generally applicable across chemical series and protein targets.

PMID- 29655613
TI  - Terpenoids isolated from Chinese liverworts Lepidozia reptans and their anti
      inflammatory activity.
AB  - Five new terpenoids (1-5) including two dollabellane-type, one ent-kaurane-type
      diterpenoids and two sesquiterpenoids were isolated from the Chinese liverwort
      Lepidozia reptans (L.) Dumort., together with nine known terpenoids (6-14). Their
      structures were determined on the basis of analysis of MS and NMR spectroscopic
      data, single-crystal X-ray diffraction and electronic circular dichroism
      calculations. The selected compounds 1, 2, 6, 7, 9 and 14 were screened for anti
      inflammatory activities by the model of LPS-induced nitric oxide (NO) production
      with macrophage cells, and the mechanism of the active compounds 1 and 2 were
      further explored.

PMID- 29655614
TI  - A brief validated screen to identify boys and girls at risk for early marijuana
      use.
AB  - To guide recruitment, the ABCD Study requires a method for identifying children
      at high risk for early-onset substance use that may be utilized during the
      recruitment process. This study was undertaken to inform the development of a
      brief screen for identifying youths' risk of early-onset substance use and other
      adverse outcomes. To be acceptable by participants in this context, consideration
      of potential items was limited to child characteristics previously determined to
      be potentially pertinent and parental cigarette smoking. To focus the analyses on
      a single target substance use outcome pertinent to the stated goals of the ABCD
      Study, early-onset marijuana use was selected. Utilizing data collected prior to
      the initiation of the ABCD Study, four longitudinal data sets were used in nine
      secondary data analyses to test, replicate and validate a brief screening
      assessment for boys and girls to identify those at risk for early-onset marijuana
      use by ages 14-15. The combination of child externalizing problems reported by
      the parent (4 items: destroys things belonging to his/her family or others;
      disobedience at school; lying or cheating; steals outside the home) and parent
      smoking (1 item) proved to be the optimal screen. This was largely replicated
      across the four data sets. Indicators of predictive efficiency were modest in
      magnitude and statistically significant in 8 out of the 9 analyses. The results
      informed the screen's optimal threshold for identifying children at risk for
      early-onset marijuana use. The addition of child internalizing problems did not
      improve these predictions. Further analyses showed the predictive utility of the
      screen for several other substance use outcomes at ages 15 to 18, including
      alcohol and nicotine use. The results support the use of a short screening
      assessment to identify youth at risk for early-onset substance use in the ABCD
      Study and other research.

PMID- 29655615
TI  - Locked nucleic acid -anti- let-7a induces apoptosis and necrosis in macrophages
      infected with Leishmania major.
AB  - BACKGROUND: Protozoan parasites of the genus Leishmania are etiologic agents
      which are intracellular pathogens of vertebrates and replicate inside infected
      macrophages. Leishmania have developed complex strategies to reverse host immune
      responses in favor of it. One of the major species causing cutaneous involvements
      is Leishmania major. MicroRNAs (miRNA) are non-coding small RNAs encoding 22
      nucleotide (nt) long RNAs. miRNAs affect diverse biological processes, including
      cell cycle, proliferation, differentiation, growth and development, metabolism,
      aging, apoptosis, gene expression and immune regulation. This study aimed at
      evaluating apoptosis and necrosis after transfection locked nucleic acid (LNA)
      inhibitor of let-7a in the human macrophages miRNAs upon infectionwith L. major.
      MATERIALS AND METHODS: Inhibition of let-7a in macrophages was derived originally
      from the human monocytes (MDM), using locked nucleic acid (LNA) antagomir. The
      total cellular RNA was extracted 24 and 48 h post transfection. The levels o Let
      7a expression was measured by qPCR Real Time using specific primer. Annexin
      V/Propidium Iodide staining method was performed to detect apoptosis and necrosis
      in the MDM cells. Data were analyzed using the Kruskal-Wallis and Mann-Whitney
      tests. RESULTS: Let-7a inhibition increased the MDM cells apoptosis and necrosis
      using flow cytometry method. CONCLUSIONS: The results suggested that inhibition
      of let-7a could be a new approach in treatment of leishmaniasis.

PMID- 29655616
TI  - Role of innate immunity in pathophysiology of classical swine fever virus
      infection.
AB  - Classical swine fever virus (CSFV) infection causes mild to severe diseases among
      pigs, depending on the age and immune status of the host and viral strains. CSFV
      targets various cells, including macrophages and conventional and plasmacytoid
      dendritic cells. Classical swine fever is one of the most devastating diseases of
      pigs which leads to high morbidity and mortality, and causes significant economic
      loss worldwide. In response to infection with CSFV, host innate immune system
      eliminates the virus by recognizing specific viral molecules via distinct
      cellular pattern recognition receptors. These receptors trigger downstream
      intracellular signaling pathways, which regulate the translocation and activation
      of transcription factors that control the production of cytokines and interferons
      (IFNs). In turn, these IFNs activate JAK-STAT signaling that governs the
      transcription of IFN-stimulated genes (ISGs) that play critical roles in
      antiviral immunity. However, CSFV has evolved different strategies to evade
      innate immune signaling and can establish persistent infection without being
      recognized by immune surveillance. In this review, we discuss the current
      understanding of host innate response to CSFV infection. We also summarize how
      CSFV evades innate immunity to establish its chronic infection.

PMID- 29655617
TI  - Novel treatment of papillomatous conjunctival lesions using pattern scanning
      laser photocoagulation: 1-Year results.
AB  - PURPOSE: To evaluate the safety and 1-year effect of pattern scanning laser
      photocoagulation treatment for pedunculated papillomatous and sessile
      conjunctival lesions in a low-resource setting with extremely limited operating
      room access. METHODS: Adult patients with clinical diagnosis of conjunctival
      papilloma underwent complete ophthalmologic exam including anterior segment
      photography. After topical anesthesia and toluidine blue 1% instillation, the
      lesion was treated by pattern scanning photocoagulation using a duration time
      that varied from 20 to 100 ms and power from 600 to 1800 mW, treating the entire
      lesion surface with a 2 mm margin. Patients were examined weekly for a month then
      monthly and underwent retreatment as necessary. RESULTS: Six patients and seven
      eyes that had clinically significant non-malignant pedunculated or sessile
      papillomatous lesions were treated. All lesions responded to treatment, with
      complete resolution after an average of 2.3 sessions. Procedures were well
      tolerated with only minor mild discomfort persisting up to two days post
      treatment. Patients were followed for a mean follow-up time of 13 months with no
      recurrences reported. CONCLUSION: Short-term results of the pattern scanning
      laser photocoagulation approach, with toluidine blue for papillomatous
      conjunctival lesions are favorable with a 100% success rate in this cohort. This
      rate is comparable to surgical excision. This novel strategy proved to be a less
      resource intensive alternative that not only could demonstrate its usefulness in
      settings with chronic operating room shortages, but also in recurrent cases.
      Longer follow-ups with a larger sample size and cost-analysis are necessary to
      confirm our findings.

PMID- 29655618
TI  - Concurrent Surgery and the Role of the Pediatric Attending Surgeon: Comparing
      Parents' and Surgeons' Expectations.
AB  - BACKGROUND: The common practice of performing concurrent or overlapping
      operations has been intensely scrutinized by lay media and academic press to
      investigate its safety and cost-effectiveness. However, there is little
      information about its use within the pediatric population. Even less is known
      about parents' expectations about the surgeon's role on the day of operation and
      how they align with those of pediatric surgeons and surgical trainees, despite
      the potential for significant discrepancies in expectations to erode trust and
      damage the physician-family relationship. STUDY DESIGN: A 5-point Likert-style
      survey was designed to characterize expectations about the degree of involvement
      by pediatric attending surgeons throughout a surgical case (1 = strongly
      disagree, 3 = neutral, 5 = strongly agree). The survey was administered to
      parents of pediatric patients undergoing elective operations during a 3-month
      interval at a single academic institution. The survey was also administered to
      surgeons and surgical residents at the same institution. Multivariate
      multiplicity-adjusted t-tests were used to identify significant differences
      between responders. RESULTS: One hundred and ten parents and 84 pediatric
      surgeons and trainees completed the survey. Parents' responses to the survey
      ranged from 4.15 to 4.89, compared with 2.75 to 4.86 from surgeons. The
      differences achieved statistical significance (p < 0.05) for 8 of 9 statements.
      Statistically significant differences were fewer, but still present, between
      attending surgeons and surgical trainees, as well as between surgeons with and
      without children. CONCLUSIONS: There is a significant mismatch between parents'
      expectations and those of pediatric surgeons about the role of the surgeon on the
      day of operation, with parents consistently expecting more direct involvement by
      the attending surgeon. These discrepancies can have implications for both
      parent/patient satisfaction and medical education.

PMID- 29655619
TI  - ?

PMID- 29655620
TI  - Identification of men with low-risk biopsy-confirmed prostate cancer as
      candidates for active surveillance.
AB  - BACKGROUND: A combined clinical cell-cycle risk (CCR) score that incorporates
      prognostic molecular and clinical information has been recently developed and
      validated to improve prostate cancer mortality (PCM) risk stratification over
      clinical features alone. As clinical features are currently used to select men
      for active surveillance (AS), we developed and validated a CCR score threshold to
      improve the identification of men with low-risk disease who are appropriate for
      AS. METHODS: The score threshold was selected based on the 90th percentile of CCR
      scores among men who might typically be considered for AS based on NCCN
      low/favorable-intermediate risk criteria (CCR = 0.8). The threshold was validated
      using 10-year PCM in an unselected, conservatively managed cohort and in the
      subset of the same cohort after excluding men with high-risk features. The
      clinical effect was evaluated in a contemporary clinical cohort. RESULTS: In the
      unselected validation cohort, men with CCR scores below the threshold had a
      predicted mean 10-year PCM of 2.7%, and the threshold significantly dichotomized
      low- and high-risk disease (P = 1.2 * 10-5). After excluding high-risk men from
      the validation cohort, men with CCR scores below the threshold had a predicted
      mean 10-year PCM of 2.3%, and the threshold significantly dichotomized low- and
      high-risk disease (P = 0.020). There were no prostate cancer-specific deaths in
      men with CCR scores below the threshold in either analysis. The proportion of men
      in the clinical testing cohort identified as candidates for AS was substantially
      higher using the threshold (68.8%) compared to clinicopathologic features alone
      (42.6%), while mean 10-year predicted PCM risks remained essentially identical
      (1.9% vs. 2.0%, respectively). CONCLUSIONS: The CCR score threshold appropriately
      dichotomized patients into low- and high-risk groups for 10-year PCM, and may
      enable more appropriate selection of patients for AS.

PMID- 29655621
TI  - The economic burden of hypertension, heart failure, myocardial infarction, and
      atrial fibrillation in Mexico.

PMID- 29655622
TI  - [Pulmonary arterial hypertension associated with human immunodeficiency virus:
      thirty years after its description].
AB  - The development of pulmonary arterial hypertension associated with human
      immunodeficiency virus reduces the probability of survival in the patient
      affected compared to those without cardiopulmonary disease. The pathophysiology
      is uncertain. There are several lines of research to associate the different
      proteins of the virus in the endothelial lesion. From a therapeutic point of view
      there are treatment modalities that allow an acceptable life expectancy.

PMID- 29655623
TI  - Insulin resistance and metabolic syndrome criteria in lean, normoglycemic college
      age subjects.
AB  - AIMS: The goal of this study was to determine insulin sensitivity in a fasted
      state and during an oral glucose tolerance test (OGTT), in normoglycemic (NGT),
      lean (L) (n = 35) and, for comparison, overweight/obese (OW/O) (n = 9) college
      aged subjects. MATERIALS AND METHODS: Insulin sensitivity for 44 NGT,
      normotensive subjects, age 18-26 yrs., was determined by homeostasis model
      assessment (HOMA-IR) and from Matsuda index (ISI Matsuda). RESULTS: Subjects were
      normoglycemic fasted (4.59 + 0.35 mmol/L) and at two hours post OGTT (4.52  +
      1.35 mmol/L). Besides anthropometric measures, there were significant differences
      between OW/O and L for fasting insulin (P < 0.001) and both measures of insulin
      sensitivity (P < 0.05). All subjects exhibited a 9-fold range in HOMA-IR (0.88 +
      0.51, range 0.3-2.7) and an 8-fold range in ISI Matsuda (11.9 + 4.7, range 3.0
      24.2). The latter was inversely correlated with systolic blood pressure (r =
      0.35, P = 0.04) even though subjects were normotensive. In lean subjects, 2.3%
      were IR by HOMA-IR > 2.1, 5.7% by ISI Matsuda < 5.9, and 22.9% had >one criteria
      for metabolic syndrome (MetS); 28.6% had some negative metabolic biomarker.
      CONCLUSIONS: Insulin resistance is present in lean, NGT college-age subjects even
      without MetS criteria and is discernable with an easily applicable OGTT-derived
      index.

PMID- 29655624
TI  - Post-immunization leucocytosis and its implications for the management of febrile
      infants.
AB  - AIMS: Clinical guidelines for management of infants with fever but no evident
      focus of infection recommend that those aged 1-3 months with a white cell count
      >15 * 109/l have a full septic screen and be admitted for parenteral antibiotics.
      However, there is limited information about leucocyte changes following routine
      immunization, a common cause of fever. We investigated white cell counts shortly
      after routine immunization in Ugandan infants under 3 months of age. METHODS:
      White cell counts were measured in 212 healthy infants following routine
      immunizations (DTwP-HepB-Hib, oral polio and pneumococcal conjugate 7 vaccines)
      received prior to 3 months of age. RESULTS: Mean leucocyte counts increased from
      9.03 * 109/l (95% confidence interval 8.59-9.47 * 109/l) pre-immunizations to
      16.46 * 109/l (15.4-17.52 * 109/l) at one-day post-immunizations at 6 weeks of
      age, and 15.21 * 109/l (14.07-16.36 * 109/l) at one-day post-immunizations at 10
      weeks of age. The leucocytosis was primarily a neutrophilia, with neutrophil
      percentages one-day post-immunization of 49% at 6 weeks of age and 46% at 10
      weeks of age. White cell parameters returned to baseline by two-days post
      immunization. No participant received antibiotics when presenting with isolated
      fever post-immunization and all remained well at follow-up. CONCLUSIONS: In our
      study almost half the children <3 months old presenting with fever but no evident
      focus of infection at one-day post-immunization met commonly used criteria for
      full septic screen and admission for parenteral antibiotics, despite having no
      serious bacterial infection. These findings add to the growing body of literature
      that questions the utility of white blood cell measurement in identification of
      young infants at risk of serious bacterial infections, particularly in the
      context of recent immunizations, and suggest that further exploration of the
      effect of different immunization regimes on white cell counts is needed. This
      observational work was nested within a clinical trial, registration number
      ISRCTN59683017.

PMID- 29655625
TI  - An improved conjugate vaccine technology; induction of antibody responses to the
      tumor vasculature.
AB  - The induction of an antibody response against self-antigens requires a conjugate
      vaccine technology, where the self-antigen is conjugated to a foreign protein
      sequence, and the co-application of a potent adjuvant. The choice of this foreign
      sequence is crucial as a very strong antibody response towards it may compromise
      the anti-self immune response. Here, we aimed to optimize the conjugate design
      for application of vaccination against the tumor vasculature, using two different
      approaches. First, the immunogenicity of the previously employed bacterial
      thioredoxin (TRX) was reduced by using a truncated from (TRXtr). Second, the
      Escherichia coli proteome was scrutinized to identify alternative proteins, based
      on immunogenicity and potency to increase solubility, suitable for use in a
      conjugate vaccine. This technology was used for vaccination against a marker of
      the tumor vasculature, the well-known extra domain B (EDB) of fibronectin. We
      demonstrate that engineering of the foreign sequence of a conjugate vaccine can
      significantly improve antibody production. The TRXtr construct outperformed the
      one containing full-length TRX, for the production of anti-self antibodies to
      EDB. In addition, efficient tumor growth inhibition was observed with the new
      TRXtr-EDB vaccine. Microvessel density was decreased and enhanced leukocyte
      infiltration was observed, indicative of an active immune response directed
      against the tumor vasculature. Summarizing, we have identified a truncated form
      of the foreign antigen TRX that can improve conjugate vaccine technology for
      induction of anti-self antibody titers. This technology was named Immuno-Boost (I
      Boost). Our findings are important for the clinical development of cancer
      vaccines directed against self antigens, e.g. the ones selectively found in the
      tumor vasculature.

PMID- 29655626
TI  - A toddler PCV booster dose following 3 infancy priming doses increases
      circulating serotype-specific IGG levels but does not increase protection against
      carriage.
AB  - BACKGROUND: We compared PCV7 serological response and protection against carriage
      in infants receiving 3 doses (2, 4, 6 months; 3+0 schedule) to those receiving a
      booster (12 months; 3+1). METHODS: A prospective, randomized controlled study,
      conducted between 2005 and 2008, before PCVs were implemented in Israel. Healthy
      infants were randomized 1:1:1 to receive 3+1, 3+0 and 0+2 (control group; 12, 18
      months doses). Nasopharyngeal/oropharyngeal swabs were obtained at all visits.
      Serum serotype-specific IgG concentrations and opsonic activities (OPA) were
      measured at 2, 7, 13 and 19 months. This study was registered with Current
      Controlled Trials, Ltd. ISRCTN28445844. RESULTS: Overall, 544 infants were
      enrolled: 3+1 (n = 178), 3+0 (n = 178) and 0+2 (n = 188). Post-priming (7
      months), antibody concentrations were similar in both groups, except for serotype
      18C (higher in 3+0). Post-booster (13, 19 months), ELISA and OPA levels were
      significantly higher in 3+1 than in 3+0 group. Nasopharyngeal/oropharyngeal
      cultures were positive for Streptococcus pneumoniae in 2673 (54.3%) visits.
      Acquisition rates (vaccine and non-vaccine serotypes) were similar for 3+1 and
      3+0 groups at 7-30 months and for 0+2 group at 19-30 months. CONCLUSIONS: PCV7
      booster after 3 priming doses increased substantially IgG concentrations but did
      not further reduced vaccine-serotype nasopharyngeal acquisition, suggesting that
      protection from pneumococcal carriage does not depend primarily on serum IgG.

PMID- 29655628
TI  - Trends in diarrhea hospitalizations among infants at three hospitals in Tanzania
      before and after rotavirus vaccine introduction.
AB  - BACKGROUND: The Tanzania Ministry of Health introduced monovalent human rotavirus
      vaccine in January 2013, to be administered at ages 6 and 10 weeks. Data suggest
      there was high vaccine uptake. We used hospital ward registers from 3 hospitals
      to examine trends in diarrhea hospitalizations among infants before and after
      vaccine introduction. METHODS: Ward registers from Dodoma Regional Referral
      Hospital (Central Tanzania), and two hospitals in Mbeya (Southwest area), Mbeya
      Zonal Referral Hospital and Mbalizi Hospital, were used to tally admissions for
      diarrhea among children by age group, month and year. Rotavirus surveillance had
      started at these hospitals in early 2013; the proportion of infants enrolled and
      rotavirus-EIA positive were examined by month to determine peak periods of
      rotavirus disease post-vaccine introduction. RESULTS: Registers were available
      for 2-4 prevaccine years and 2-3 post introduction years. At Dodoma Regional
      Referral Hospital, compared with the mean of 2011 and 2012, diarrhea
      hospitalizations among infants were 26% lower in 2015 and 58% lower in 2016. The
      diarrhea peak shifted later in the year first by 1 and then by 2-3 months from
      prevaccine. At the Mbeya hospitals, the number of diarrhea admissions in
      prevaccine period varied substantially by year. At Mbeya Referral Hospital,
      diarrhea hospitalizations among infants were lower by 25-37% in 2014 and 11-26%
      in 2015, while at Mbalizi Hospital, these hospitalizations were 4% lower in 2014
      and 14% higher in 2015. Rotavirus testing data demonstrated a lowering of the
      prevaccine peak, a shift in timing of the peak months and indicated that other
      diarrheal peaks in post-introduction years were not due to rotavirus.
      CONCLUSIONS: In this ecological evaluation, total diarrhea hospitalizations among
      infants were lower (>=25% lower in >=1 year) following introduction in 2 of 3
      hospitals. There are challenges in using ward registers to ascertain possible
      impact of rotavirus vaccine introduction on trends in hospitalizations for
      treatment of all diarrheal illness.

PMID- 29655627
TI  - Lipopolysaccharide-specific memory B cell responses to an attenuated live cholera
      vaccine are associated with protection against Vibrio cholerae infection.
AB  - BACKGROUND: The single-dose live attenuated vaccine CVD 103-HgR protects against
      experimental Vibrio cholerae infection in cholera-naive adults for at least 6
      months after vaccination. While vaccine-induced vibriocidal seroconversion is
      associated with protection, vibriocidal titers decline rapidly from their peak 1
      2 weeks after vaccination. Although vaccine-induced memory B cells (MBCs) might
      mediate sustained protection in individuals without detectable circulating
      antibodies, it is unknown whether oral cholera vaccination induces a MBC
      response. METHODS: In a study that enrolled North American adults, we measured
      lipopolysaccharide (LPS)- and cholera toxin (CtxB)-specific MBC responses to
      PXVX0200 (derived from the CVD 103-HgR strain) and assessed stool volumes
      following experimental Vibrio cholerae infection. We then evaluated the
      association between vaccine-induced MBC responses and protection against cholera.
      RESULTS: There was a significant increase in % CT-specific IgG, % LPS-specific
      IgG, and % LPS-specific IgA MBCs which persisted 180 days after vaccination as
      well as a significant association between vaccine-induced increase in % LPS
      specific IgA MBCs and lower post-challenge stool volume (r = -0.56, p < 0.001).
      DISCUSSION: Oral cholera vaccination induces antigen-specific MBC responses, and
      the anamnestic LPS-specific responses may contribute to long-term protection and
      provide correlates of the duration of vaccine-induced protection. CLINICAL TRIALS
      REGISTRATION: NCT01895855.

PMID- 29655629
TI  - Intramuscular vaccination of guinea pigs with the live-attenuated human herpes
      simplex vaccine VC2 stimulates a transcriptional profile of vaginal Th17 and
      regulatory Tr1 responses.
AB  - Herpes simplex virus is a common causative agent of oral and genital diseases.
      Novel vaccines and therapeutics are needed to combat herpes infections especially
      after the failure of subunit vaccines in human clinical trials. We have shown
      that the live-attenuated HSV-1 VC2 vaccine strain is unable to establish latency
      in vaccinated animals and produces a robust immune response capable of completely
      protecting mice against lethal vaginal HSV-1 or HSV-2 infections. The guinea pig
      represents the best small animal model of genital HSV-2 disease. Reported here,
      twenty-one female Hartley guinea pigs received intramuscular injection with
      either the VC2 vaccine, or equal volume of conditioned tissue culture media.
      Animals received 2 booster vaccinations at 21 day intervals following the initial
      vaccination. After vaccination, animals were challenged with the highly virulent
      HSV-2 (G) strain. Histologically, VC2 vaccinated animals had little to no
      apparent inflammation/disease following challenge. Unvaccinated animals developed
      moderate to severe erosive and ulcerative vaginitis. Quantitative reverse
      transcriptase PCR analysis in VC2 vaccinated and challenged animals identified
      transcriptional signatures of Th17 and regulatory Tr1 cells associated with the
      inflammatory response primed by VC2 vaccination. Treatment of cultured human
      vaginal epithelial cells (VK2 cells) with a combination of IL-17A and IL-22
      resulted in the significant induction of beta-defensin 3 expression. Further,
      treatment of VK2 cells with IL-17A, IL-22, IL-36 or beta-defensin 3 resulted in
      diminished HSV-2 replication. Overall, these results suggest that intramuscular
      vaccination with the live-attenuated vaccine VC2 primes a mucosal immune response
      predisposing the adaptive expression of transcripts associated with a Th17
      response to challenge and these responses contribute to antiviral immunity.

PMID- 29655630
TI  - Is varicella vaccination associated with pediatric arterial ischemic stroke? A
      population-based cohort study.
AB  - BACKGROUND AND PURPOSE: Varicella disease is a risk factor for pediatric Arterial
      Ischemic Stroke (AIS). Isolated case reports have emerged suggesting that
      varicella vaccination may also pose a risk for AIS. METHODS: This retrospective
      population-based cohort study assessed the risk of AIS in children who received a
      varicella-containing vaccine, as compared to those who did not. The study cohort
      consisted of children born between January 1, 2006 and December 31, 2013, in the
      Canadian province of Alberta, where all routine childhood vaccinations are
      publicly-funded, and recorded in a central immunization repository. These data
      were linked with hospital discharge abstract data to identify children diagnosed
      with AIS. A Cox proportional hazard model assessed the risk of AIS in the 12
      months following vaccination for children receiving a varicella vaccine between
      11 and 23 months of age, as compared to non-vaccinated children. RESULTS: Of the
      368,992 children in the cohort, 325,729 were vaccinated with a varicella
      containing vaccine between 11 and 23 months of age. The rate of AIS was 7.8 (95%
      CI 4.8-10.9) per 100,000 person years at risk in the 12 months following
      varicella vaccination, as compared to 6.8 (95% CI 1.3-12.2) for children who did
      not receive a varicella vaccine. The adjusted Hazard Ratio for the risk of AIS,
      controlling for other AIS risk factors, in vaccinated children as compared to non
      vaccinated children was 1.6 (95% CI 0.7-3.7) in the 12 months following
      vaccination and 1.7 (95% CI 0.5-4.9) in the 30 days following vaccination.
      CONCLUSIONS: Our study found no evidence of an increased risk of AIS following
      varicella vaccination. This population-based cohort study provides reassurance to
      parents and clinicians regarding the safety of varicella vaccination.

PMID- 29655631
TI  - Detection of rotavirus before and after monovalent rotavirus vaccine introduction
      and vaccine effectiveness among children in mainland Tanzania.
AB  - BACKGROUND: Monovalent rotavirus vaccine (RV1) was introduced in Tanzania in
      January 2013 under the Reach Every Child initiative, to be given at ages 6 and 10
      weeks. We used the sentinel hospital rotavirus surveillance system to examine the
      rotavirus detection rate before and after vaccine introduction and estimate
      vaccine effectiveness. METHODS: Before vaccine introduction, rotavirus
      surveillance was established at two mainland hospitals; children admitted for
      acute diarrhea were eligible for enrollment and stools were tested for rotavirus
      antigen. We compared the rotavirus positivity rate in the pre-vaccine period
      (Tanga Hospital, 2009 and 2011; Bugando Medical Centre, 2012) to that from post
      introduction years, 2014-2015. In 2013, surveillance was established at 9
      additional hospitals. We examined rotavirus positivity among infants at these
      sites for 2014-2015. We obtained vaccine records and calculated vaccine
      effectiveness at 3 sites using case-test-negative control design. RESULTS: At
      Tanga Hospital, the rotavirus positivity rate among infants was 41% (102/251) pre
      vaccine and 14% (28/197) in post-vaccine years (rate ratio: 0.35 [95% CI 0.22
      0.54]). At Bugando, the positivity rate was 58% (83/143) pre-vaccine, and 18%
      (49/277) post-introduction (rate ratio 0.30 [95% CI 0.210.44]). Results were
      similar among children <5 years. At the new sites, the median site rotavirus
      positivity rate among infants was 26% in 2014 (range 19-44%) and 18% in 2015
      (range 16-33%). The effectiveness of >=1 RV1 dose against rotavirus
      hospitalization among children 5-23 months was 53% (95% CI: -14, 81), and 66%
      (95% CI: 9-87) against hospitalization with intravenous rehydration. Following
      introduction, peak rotavirus activity occurred later in the year and appeared
      more concentrated in time. CONCLUSION: Rotavirus surveillance data from Tanzania
      indicate that the rotavirus positivity rate among children hospitalized with
      diarrhea that were enrolled was substantially reduced after vaccine introduction.
      Low positivity rates among infants were detected at hospitals across the country.
      Overall, the data support that rotavirus vaccine has been successfully introduced
      and is effective in Tanzanian children.

PMID- 29655633
TI  - Vaccine Technology VI: Innovative and integrated approaches in vaccine
      development.

PMID- 29655632
TI  - Ag85A-specific CD4+ T cell lines derived after boosting BCG-vaccinated cattle
      with Ad5-85A possess both mycobacterial growth inhibition and anti-inflammatory
      properties.
AB  - There is a need to improve the efficacy of the BCG vaccine against human and
      bovine tuberculosis. Previous data showed that boosting bacilli Calmette-Guerin
      (BCG)-vaccinated cattle with a recombinant attenuated human type 5 adenovirally
      vectored subunit vaccine (Ad5-85A) increased BCG protection and was associated
      with increased frequency of Ag85A-specific CD4+ T cells post-boosting. Here, the
      capacity of Ag85A-specific CD4+ T cell lines - derived before and after viral
      boosting - to interact with BCG-infected macrophages was evaluated. No difference
      before and after boosting was found in the capacity of these Ag85A-specific CD4+
      T cell lines to restrict mycobacterial growth, but the secretion of IL-10 in
      vitro post-boost increased significantly. Furthermore, cell lines derived post
      boost had no statistically significant difference in the secretion of pro
      inflammatory cytokines (IL-1beta, IL-12, IFNgamma or TNFalpha) compared to pre
      boost lines. In conclusion, the protection associated with the increased number
      of Ag85A-specific CD4+ T cells restricting mycobacterial growth may be associated
      with anti-inflammatory properties to limit immune-pathology.

PMID- 29655634
TI  - Anti PAD autoimmunity and rheumatoid arthritis.

PMID- 29655635
TI  - Percutaneous endobiliary radiofrequency ablation for refractory benign
      hepaticojejunostomy and biliary strictures.
AB  - PURPOSE: The objective of this study was to determine the safety and efficacy of
      percutaneous endobiliary radiofrequency ablation (ERFA) and balloon dilation for
      the treatment of hepaticojejunostomy (HJ) strictures resistant to surgery and/or
      other interventions. MATERIALS AND METHODS: Eighteen patients who underwent
      percutaneous ERFA for HJ stricture were included. There were 10 men and 8 women
      with a mean age of 48.3+/-10.8 (SD) years (range: 33-69 years). The 18 patients
      had a total of 29 benign HJ strictures secondary to cholecystectomy (14 patients;
      78.0%), Whipple procedure (3 patients; 16.6%) or blunt abdominal trauma (1
      patient; 5.4%). The different end-points were technical success, clinical
      success, recurrence, procedure-related mortality, and morbidity. RESULTS:
      Technical and clinical success rates were 100% and 83.3%, respectively. No
      mortality and major procedure-related complications were observed. One patient
      experienced minor complication (self-limited pleural effusion). Two patients did
      not show favorable response to ERFA whereas 10 patients had no stricture
      recurrence during a mean follow-up period of 7.3 months+/-1.0 (SD) (range: 4-10
      months). CONCLUSION: ERFA is a safe and effective treatment for benign HJ and
      biliary strictures. However, more studies involving more patients with a long
      term follow-up period should be made to fully determine the long-term results of
      ERFA.

PMID- 29655636
TI  - Reticulocyte hemoglobin content in a large sample of the general Dutch population
      and its relation to conventional iron status parameters.
AB  - BACKGROUND: No full consensus exists on which iron status parameters to use for
      iron status assessment. In this study, we assessed the usefulness of measurement
      of the hemoglobin content of reticulocytes (CHr) in the general population.
      METHODS: The following iron status parameters were assessed in 1024 adults: CHr,
      reticulocytes, hemoglobin (Hb), ferritin, serum iron, transferrin, transferrin
      saturation and mean corpuscular volume (MCV). Mean parameter values and
      correlation coefficients for CHr and other parameters were calculated. In
      addition, mean CHr levels in subgroups based on low and normal values of other
      iron status parameters were compared. RESULTS: Mean CHr values in men were 31.81
      (SD = 1.50) pg and in women 31.32 (SD = 1.51) pg. A positive correlation was
      observed between CHr and Hb, ferritin, serum iron, transferrin saturation and
      MCV; a negative correlation was observed between CHr and transferrin. CHr levels
      were lower in subjects with low values of Hb, ferritin, serum iron and MCV
      compared to subjects with normal values for these parameters. CONCLUSION: Mean
      CHr values in this population were comparable to values reported in small healthy
      control groups. Associations with other parameters were in agreement with
      associations reported in literature. CHr measurement might have additional value
      in iron status assessment.

PMID- 29655637
TI  - Analysis of human blood plasma cell-free DNA fragment size distribution using
      EvaGreen chemistry based droplet digital PCR assays.
AB  - BACKGROUND: Plasma cell-free DNA (cfDNA) fragment size distribution provides
      important information required for diagnostic assay development. We have
      developed and optimized droplet digital PCR (ddPCR) assays that quantify short
      and long DNA fragments. These assays were used to analyze plasma cfDNA fragment
      size distribution in human blood. METHODS: Assays were designed to amplify
      76,135, 490 and 905 base pair fragments of human beta-actin gene. These assays
      were used for fragment size analysis of plasma cell-free, exosome and apoptotic
      body DNA obtained from normal and pregnant donors. RESULTS: The relative
      percentages for 76, 135, 490 and 905 bp fragments from non-pregnant plasma and
      exosome DNA were 100%, 39%, 18%, 5.6% and 100%, 40%, 18%,3.3%, respectively. The
      relative percentages for pregnant plasma and exosome DNA were 100%, 34%, 14%,
      23%, and 100%, 30%, 12%, 18%, respectively. The relative percentages for non
      pregnant plasma pellet (obtained after 2nd centrifugation step) were 100%, 100%,
      87% and 83%, respectively. CONCLUSION: Non-pregnant Plasma cell-free and exosome
      DNA share a unique fragment distribution pattern which is different from pregnant
      donor plasma and exosome DNA fragment distribution indicating the effect of
      physiological status on cfDNA fragment size distribution. Fragment distribution
      pattern for plasma pellet that includes apoptotic bodies and nuclear DNA was
      greatly different from plasma cell-free and exosome DNA.

PMID- 29655638
TI  - Attenuation of the Niemann-Pick type C2 disease phenotype by intracisternal
      administration of an AAVrh.10 vector expressing Npc2.
AB  - Niemann-Pick type C2 (NPC2) disease is a rare, neurodegenerative disorder caused
      by mutations in the NPC2 gene, leading to lysosomal accumulation of unesterified
      cholesterol and other lipids. It is characterized by hepatosplenomegaly, liver
      dysfunction and severe neurological manifestations, resulting in early death.
      There is no effective therapy for NPC2 disease. Here, we evaluated the
      effectiveness of an adeno-associated virus (AAV), serotype rh.10 gene transfer
      vector expressing the mouse Npc2 gene (AAVrh.10-mNpc2-HA, HA tagged to facilitate
      analysis) to treat the disease in an Npc2-/- mouse model. A single intracisternal
      administration of the AAVrh.10-mNpc2-HA to 6 week old Npc2-/- mice mediated
      vector DNA, transgene mRNA and protein expression in brain and other organs.
      Compared to untreated Npc2-/- mice, AAV-treated Npc2-/- mice demonstrated
      amelioration of disease pathology in the brain, reduced lysosomal storage,
      reduced Purkinje cell death, decreased gliosis, and improved performance in
      behavioral tasks. Treatment-related reduction in serum disease markers was
      detected early and this effect persisted. Liver and spleen pathology were
      improved with significant reduction of liver cholesterol and sphingomyelin levels
      in treated Npc2-/- mice. Finally, administration of AAVrh.10-mNpc2-HA
      significantly extended life-span. Taken together, these data demonstrate the
      benefit of a one-time intracisternal administration of AAVrh.10-mNpc2-HA as a
      life-long treatment for NPC2 disease.

PMID- 29655639
TI  - Glia maturation factor beta is required for reactive gliosis after traumatic
      brain injury in zebrafish.
AB  - Gliosis is a hallmark of neural pathology that occurs after most forms of central
      nervous system (CNS) injuries including traumatic brain injury (TBI).
      Identification of genes that control gliosis may provide novel treatment targets
      for patients with diverse CNS injuries. Glia maturation factor beta (GMFB) is
      crucial in brain development and stress response. In the present study, GMFB was
      found to be widely expressed in adult zebrafish telencephalon. A gmfb mutant
      zebrafish was created using CRISPR/cas9. In the uninjured zebrafish
      telencephalon, glial fibrillary acidic protein (GFAP) fibers in gmfb mutants were
      disorganized and shorter than wild type zebrafish. After TBI, transformation of
      quiescent type I radial glial cells (RGC) to proliferative type II RGCs was
      significantly suppressed in the gmfb mutant. RGC proliferation and hypertrophy
      post-TBI was reduced in gmfb mutants, indicating that reactive gliosis was
      attenuated. TBI-induced acute inflammation was also found to be alleviated in the
      gmfb mutant. Morphological changes also suggest attenuation of microglial
      reactive gliosis. In a mouse model of TBI, GMFB expression was increased around
      the injury site. These GMFB+ cells were identified as astrocytes and microglia.
      Taken together, the data suggests that GMFB is not only required for normal
      development of GFAP fibers in the zebrafish telencephalon, but also promotes
      reactive gliosis after TBI. Our findings provide novel information to help better
      understand the reactive gliosis process following TBI.

PMID- 29655641
TI  - Is Newer Necessarily Better? The Evolution of Incisional Glaucoma Surgery Over
      the Last 100 Years.
AB  - PURPOSE: To examine the progress made in glaucoma incisional surgery and
      determine if there has been sufficient progress to meet the needs of glaucoma
      patients. DESIGN: Perspective (literature review). METHODS: This is a
      retrospective assessment of key milestones in the evolution of glaucoma
      incisional surgery and an evaluation of the risks and the benefits of these
      procedures. Benefits are defined as effective reduction in intraocular pressure
      (IOP) and protecting visual function, while risks are defined as safety and
      complications for our patients. Quality of life is also considered. RESULTS:
      Although advances have been made in the last 100 years, the trabeculectomy, a
      procedure that was described more than 50 years ago, remains the optimal choice
      for reducing IOP among those patients who require pressures in the teens, who do
      not respond to medications and prior laser therapy. CONCLUSIONS: Appropriate
      patient selection, careful attention to surgical technique, and intensive follow
      up of patients will optimize the results of a trabeculectomy. Newer procedures
      must be carefully studied in well-designed clinical trials to determine
      comparative levels of safety and efficacy to this gold standard. Advances in drug
      delivery and minimally invasive glaucoma surgery may ultimately produce the best
      outcome for glaucoma patients in the future.

PMID- 29655640
TI  - How Are Ocular Signs and Symptoms of Dry Eye Associated With Depression in Women
      With and Without Sjogren Syndrome?
AB  - PURPOSE: To determine whether ocular phenotypic features of keratoconjunctivitis
      sicca (KCS) and/or participant-reported symptoms of dry eye disease are
      associated with depression in women participants enrolled in the Sjogren's
      International Collaborative Clinical Alliance (SICCA). DESIGN: Cross-sectional
      study. METHODS: Women enrolled in the SICCA registry from 9 international
      research sites. Participants met at least 1 of 5 inclusion criteria for registry
      enrollment (including complaints of dry eyes or dry mouth, a previous diagnosis
      of Sjogren syndrome (SS), abnormal serology (positive anti-Sjogren syndrome
      antigen A and/or B [anti-SSA and/or anti-SSB]), or elevated antinuclear antibody
      and rheumatoid factor), bilateral parotid gland enlargement, or multiple dental
      caries). At baseline, participants had oral, ocular, and rheumatologic
      examination; blood and saliva collection; and a labial salivary gland biopsy
      (LSGB). They also completed an interview and questionnaires including assessment
      of depression with the Patient Health Questionnaire 9 (PHQ-9). Univariate
      logistic regression was used to assess the association between depression and
      demographic characteristics, participant-reported health, phenotypic features of
      Sjogren syndrome, and participant-reported symptoms. Mixed-effects modeling was
      performed to determine if phenotypic features of KCS and/or participant-reported
      symptoms of dry eye disease were associated with depression, controlling for
      health, age, country or residence, and sex and allowing for nonindependence
      within geographic site. RESULTS: Dry eye complaints produced a 1.82-fold (95%
      confidence interval [CI] 1.38-2.40) higher odds of having depression compared to
      being symptom-free (P < .001). Additionally, complaints of specific ocular
      sensations were associated with a higher odds of depression including burning
      sensation (odds ratio 2.25, 95% CI 1.87-2.72, P < .001) compared to those without
      complaints. In both women with and without SS, the presence of symptoms of dry
      eyes and/or dry mouth rather than SS itself resulted in higher odds of
      depression. One particular ocular phenotypic feature of SS, a positive ocular
      staining score, was inversely correlated with depression. CONCLUSIONS:
      Participant-reported eye symptoms, particularly specific ocular sensations such
      as burning, were found to be positively associated with individual American
      College of Rheumatology/EUropean League Against Rheumatism (ACR/EULAR) SS
      criteria items.

PMID- 29655642
TI  - Estimating Medicare and Patient Savings From the Use of Bevacizumab for the
      Treatment of Exudative Age-related Macular Degeneration.
AB  - PURPOSE: The Medicare cost savings from the use of bevacizumab in the United
      States for the treatment of exudative age-related macular degeneration (AMD) were
      estimated by replacing the use of bevacizumab with ranibizumab and aflibercept.
      DESIGN: Retrospective trend study. METHODS: Main outcome measures were spending
      by Medicare as tracked by Current Procedural Terminology (CPT) codes for
      intravitreal injections (67028) and treatment-specific J-codes (J0178, J2778,
      J9035, J3490, and J3590) for inhibitors of vascular endothelial growth factor.
      These claims were identified from the Medicare Provider Utilization and Payment
      Data from the Centers for Medicare and Medicaid Services among fee-for-service
      (FFS) Medicare beneficiaries from 2012 to 2015. The 2008 claims were acquired
      from the 100% fee-for-service (FFS) Part B Medicare Claims File. RESULTS: The use
      of bevacizumab from 2008 to 2015 resulted in an estimated savings of $17.3
      billion, which corresponded to a $13.8 billion savings to Medicare and a $3.5
      billion savings to patients. This amount underestimated the actual cost savings
      to Medicare providers, since approximately 30% of Medicare-eligible recipients
      received care within Medicare Advantage plans and were not included in this
      analysis. CONCLUSIONS: The cost savings from the use of bevacizumab from 2008 to
      2015 for Medicare fee-for-service patients undergoing treatment for exudative AMD
      was estimated at $17.3 billion. Additional savings over the $17.3 billion would
      have accrued from the use of bevacizumab if diagnostic categories such as
      diabetic macular edema and retinal vein occlusion were included in this study.

PMID- 29655643
TI  - Automated Segmentation of Lesions Including Subretinal Hyperreflective Material
      in Neovascular Age-related Macular Degeneration.
AB  - PURPOSE: To evaluate an automated segmentation algorithm with a convolutional
      neural network (CNN) to quantify and detect intraretinal fluid (IRF), subretinal
      fluid (SRF), pigment epithelial detachment (PED), and subretinal hyperreflective
      material (SHRM) through analyses of spectral-domain optical coherence tomography
      (SD-OCT) images from patients with neovascular age-related macular degeneration
      (nAMD). DESIGN: Reliability and validity analysis of a diagnostic tool. METHODS:
      We constructed a dataset including 930 B-scans from 93 eyes of 93 patients with
      nAMD. A CNN-based deep neural network was trained using 11 550 augmented images
      derived from 550 B-scans. The performance of the trained network was evaluated
      using a validation set including 140 B-scans and a test set of 240 B-scans. The
      Dice coefficient, positive predictive value (PPV), sensitivity, relative area
      difference (RAD), and intraclass correlation coefficient (ICC) were used to
      evaluate segmentation and detection performance. RESULTS: Good agreement was
      observed for both segmentation and detection of lesions between the trained
      network and clinicians. The Dice coefficients for segmentation of IRF, SRF, SHRM,
      and PED were 0.78, 0.82, 0.75, and 0.80, respectively; the PPVs were 0.79, 0.80,
      0.75, and 0.80, respectively; and the sensitivities were 0.77, 0.84, 0.73, and
      0.81, respectively. The RADs were -4.32%, -10.29%, 4.13%, and 0.34%,
      respectively, and the ICCs were 0.98, 0.98, 0.97, and 0.98, respectively. All
      lesions were detected with high PPVs (range 0.94-0.99) and sensitivities (range
      0.97-0.99). CONCLUSIONS: A CNN-based network provides clinicians with
      quantitative data regarding nAMD through automatic segmentation and detection of
      pathologic lesions, including IRF, SRF, PED, and SHRM.

PMID- 29655644
TI  - Long-term Changes in Anterior Segment Characteristics of Eyes With Different
      Primary Angle-Closure Mechanisms.
AB  - PURPOSE: To assess long-term changes in the anterior segment (AS) of eyes with
      different angle-closure mechanisms. DESIGN: Retrospective cohort study. METHODS:
      In total, 133 eyes (from 75 participants) with angle closure were enrolled. All
      eyes received laser iridotomy (LI) during the follow-up period. Serial anterior
      segment optical coherence tomography (AS-OCT) imaging was performed during a mean
      follow-up of 4 years. Participants were categorized into 4 groups according to
      angle-closure mechanisms, based on baseline AS-OCT images: pupillary block (PB),
      plateau iris configuration (PIC), thick peripheral iris roll (TPIR), and
      exaggerated lens vault (ELV). Linear mixed-effect models were applied to evaluate
      the longitudinal changes in AS-OCT parameters (anterior chamber depth [ACD], lens
      vault [LV], and angle opening distance [AOD]). RESULTS: Forty-six eyes (35%) were
      classified as PB, 30 (23%) as PIC, 34 (26%) as TPIR, and 23 (17%) as ELV. The
      follow-up period was 41-54 months. At baseline, ACD was shallowest in ELV,
      followed by PB, TPIR, and PIC, in order. The PIC group showed significantly wider
      AOD than the other groups at baseline. ACD decreased and LV increased over time
      in all groups, especially in the PIC group. After LI, the angle widened in the PB
      and TPIR groups, but not in the PIC and ELV groups. CONCLUSIONS: AS parameters
      changed differently in the 4 groups. The effects of LI on AOD also differed among
      groups. Identification of the angle-closure mechanism may help predict
      progressive changes in AS parameters in eyes with angle closure.

PMID- 29655646
TI  - 5 G wireless telecommunications expansion: Public health and environmental
      implications.
AB  - The popularity, widespread use and increasing dependency on wireless technologies
      has spawned a telecommunications industrial revolution with increasing public
      exposure to broader and higher frequencies of the electromagnetic spectrum to
      transmit data through a variety of devices and infrastructure. On the horizon, a
      new generation of even shorter high frequency 5G wavelengths is being proposed to
      power the Internet of Things (IoT). The IoT promises us convenient and easy
      lifestyles with a massive 5G interconnected telecommunications network, however,
      the expansion of broadband with shorter wavelength radiofrequency radiation
      highlights the concern that health and safety issues remain unknown. Controversy
      continues with regards to harm from current 2G, 3G and 4G wireless technologies.
      5G technologies are far less studied for human or environmental effects. It is
      argued that the addition of this added high frequency 5G radiation to an already
      complex mix of lower frequencies, will contribute to a negative public health
      outcome both from both physical and mental health perspectives. Radiofrequency
      radiation (RF) is increasingly being recognized as a new form of environmental
      pollution. Like other common toxic exposures, the effects of radiofrequency
      electromagnetic radiation (RF EMR) will be problematic if not impossible to sort
      out epidemiologically as there no longer remains an unexposed control group. This
      is especially important considering these effects are likely magnified by
      synergistic toxic exposures and other common health risk behaviors. Effects can
      also be non-linear. Because this is the first generation to have cradle-to-grave
      lifespan exposure to this level of man-made microwave (RF EMR) radiofrequencies,
      it will be years or decades before the true health consequences are known.
      Precaution in the roll out of this new technology is strongly indicated. This
      article will review relevant electromagnetic frequencies, exposure standards and
      current scientific literature on the health implications of 2G, 3G, 4G exposure,
      including some of the available literature on 5G frequencies. The question of
      what constitutes a public health issue will be raised, as well as the need for a
      precautionary approach in advancing new wireless technologies.

PMID- 29655645
TI  - Proton Beam Irradiation: A Safe Procedure in Postequatorial Extraocular Extension
      From Uveal Melanoma.
AB  - PURPOSE: This study was performed to show long-term outcomes concerning
      metastasis rates and local recurrence rates after primary proton beam therapy in
      uveal melanoma with posterior extraocular extension (EOE) with the main focus on
      optic nerve invasion. DESIGN: Retrospective case series. METHODS: All patients
      treated with primary proton beam therapy for choroidal or ciliary body melanoma
      with posterior EOE between July 1998 and August 2010 were included. EOE was
      detected either upon sonography at primary examination or during the surgical
      application of tantalum clips onto the sclera. Ultrasound was performed in each
      patient before surgery, and if EOE was detected, a magnetic resonance imaging
      (MRI) scan was performed to confirm EOE. All patients with tumors exceeding 6 mm
      in thickness or abutting the optic disc received a 1.5 Tesla MRI scan after clip
      surgery. To assess EOE during follow-up, either ultrasound examinations or-if
      initially detected only by MRI-MRI scans were performed during follow-up.
      RESULTS: A total of 27 patients underwent primary proton beam therapy. The EOE
      was separated into 3 growth types: optic nerve infiltration in 10 patients,
      vortex vein infiltration in 9 patients, and transscleral growth postequatorially
      in 8 patients. No local recurrences were found during the overall median follow
      up of 80 months (11-168 months). Metastasis rates correlated with AJCC stages but
      not EOE volume. CONCLUSION: This study shows that posterior EOE can safely be
      treated by proton beam therapy, even if the optic nerve is infiltrated. MRI
      enables safe detection of optic nerve invasion.

PMID- 29655647
TI  - Concerns about the study of septic predictor index as a novel tool in detecting
      thermally injured patients susceptible to sepsis.

PMID- 29655648
TI  - Osteomyelitis of the First Metatarsal Head Treated With Joint-Preserving Surgery
      and a Synthetic Resorbable Bone Graft Substitute: A Case Report.
AB  - Managing infections of the first metatarsophalangeal joint can be demanding
      because many patients present with late-stage infection and partial or total
      amputation of the first ray or the phalanx could be necessary. We describe such a
      patient who was successfully treated with a calcium-based resorbable bone
      substitute that preserved the first metatarsophalangeal joint. A 38-year-old
      female presented to our department with a foot infection. Examination revealed a
      methicillin-susceptible Staphylococcus aureus infection of the first
      metatarsophalangeal joint. The histopathologic findings confirmed active
      osteomyelitis of the first metatarsal head. The metatarsophalangeal joint was
      debrided with open synovectomy, the metatarsal head was curetted, and the bone
      defect was filled with 2 mL of a synthetic bone graft substitute. Two years
      later, she reported no problems with function or pain, the joint had full range
      of motion, and she had no local or systemic signs of infection. The most recent
      radiographs revealed no damage to the first metatarsophalangeal joint. A
      synthetic bone graft substitute can be a good alternative for treating forefoot
      infections when the soft tissues are intact and the bone defect is not so large
      that partial or full amputation is necessary.

PMID- 29655649
TI  - Clinical Outcomes of the Modified Brostrom Technique in the Management of Chronic
      Ankle Instability After Early, Intermediate, and Delayed Presentation.
AB  - The modified Brostrom technique (MBT) is considered the reference standard for
      surgical management of ankle instability, with good short-term outcomes. However,
      limited evidence is available regarding outcomes for delayed presentations of
      instability. We report our outcomes for patients who underwent ligament repair
      using the MBT, from a single-surgeon retrospective study of consecutive patients.
      The minimum postoperative follow-up period was 6 months during a 5-year study
      period. The patients were retrospectively divided into 3 groups according to the
      delay in presentation: group 1, 6 months to 2 years; group 2, 2 to 4 years; and
      group 3, >4 years. We collected data on patient demographics, injury pattern, and
      intraoperative surgeon findings. The American Orthopaedic Foot and Ankle Society
      (AOFAS) ankle-hindfoot scale (AHS) was used to evaluate patient outcomes and
      satisfaction with surgery. Twenty-six patients were treated with MBT. The mean
      follow-up period was 36.9 (range 6-42) months. Twenty-five (96.2%) patients had
      unilateral injuries, and 1 (3.85%) had bilateral repairs. Of the 26 patients, 21
      (80.8%) completed the AOFAS-AHS, with a mean score of 87.4 (range 12 to 100). The
      mean interval from injury to surgery was 47.9 months. The results were excellent
      in 15 (71.4%), good in 3 (14.3%), fair in 1 (4.8%), and poor in 2 (9.5%) using
      the AOFAS-AHS. We found no significant difference in the overall AOFAS-AHS score
      or postoperative satisfaction among the groups (p > .05). All patients had a
      stable ankle joint at their final follow-up visit. In conclusion, patients with
      persistent or chronic ankle instability have good clinical outcomes and
      satisfaction after the MBT, irrespective of the time from injury to presentation.

PMID- 29655650
TI  - Surgical Treatment of Lisfranc Injury With Plantar Plate Approach.
AB  - Midfoot injuries are the second most common athletic foot injury documented in
      the published data. High-energy Lisfranc dislocations are commonly seen secondary
      to traumatic etiologies and disrupt the strong midfoot ligaments supporting the
      arch. These injuries require immediate surgical intervention to prevent serious
      complications such as compartment syndrome and amputation. The present case
      series reports a new Lapidus plate system used in 3 patients who underwent
      arthrodesis procedures for Lisfranc joint dislocation. Three patients in their
      fourth to fifth decade of life presented with a traumatic injury at the Lisfranc
      joint and subsequently underwent open reduction and internal fixation using the
      plantar Lapidus Plate System (LPS; Arthrex, Naples, FL). The LPS was placed in a
      predetermined safe zone, with measures taken to avoid the insertional points of
      the tibialis anterior and peroneus longus tendons. Radiographs were obtained for
      <=6 months postoperatively and revealed consolidation across the fusion site,
      intact hardware, and satisfactory alignment. On examination, the corrections were
      well maintained and free of signs of infection. Clinical evaluation showed no
      indication of motion within the tarsometatarsal joint and no tenderness to
      palpation surrounding the fusion sites. All 3 patients successfully returned to
      their activities of daily living without discomfort or pain. Modern surgical
      treatment of Lisfranc injuries most commonly includes open reduction and internal
      fixation, accompanied by arthrodesis. The present case series has demonstrated
      that the LPS provides relief, stability, and compression of the joint in our
      small cohort of patients who experienced a traumatic injury to the Lisfranc
      joint.

PMID- 29655651
TI  - Single and simultaneous binary mergers in Wright-Fisher genealogies.
AB  - The Kingman coalescent is a commonly used model in genetics, which is often
      justified with reference to the Wright-Fisher (WF) model. Current proofs of
      convergence of WF and other models to the Kingman coalescent assume a constant
      sample size. However, sample sizes have become quite large in human genetics.
      Therefore, we develop a convergence theory that allows the sample size to
      increase with population size. If the haploid population size is N and the sample
      size is N1/3-epsilon, epsilon>0, we prove that Wright-Fisher genealogies involve
      at most a single binary merger in each generation with probability converging to
      1 in the limit of large N. Single binary merger or no merger in each generation
      of the genealogy implies that the Kingman partition distribution is obtained
      exactly. If the sample size is N1/2-epsilon, Wright-Fisher genealogies may
      involve simultaneous binary mergers in a single generation but do not involve
      triple mergers in the large N limit. The asymptotic theory is verified using
      numerical calculations. Variable population sizes are handled algorithmically. It
      is found that even distant bottlenecks can increase the probability of triple
      mergers as well as simultaneous binary mergers in WF genealogies.

PMID- 29655652
TI  - Protective role of rosmarinic acid on amyloid beta 42-induced echoic memory
      decline: Implication of oxidative stress and cholinergic impairment.
AB  - In the present study, we examined whether rosmarinic acid (RA) reverses amyloid
      beta (Abeta) induced reductions in antioxidant defense, lipid peroxidation,
      cholinergic damage as well as the central auditory deficits. For this purpose,
      Wistar rats were randomly divided into four groups; Sham(S), Sham + RA (SR),
      Abeta42 peptide (Abeta) and Abeta42 peptide + RA (AbetaR) groups. Rat model of
      Alzheimer was established by bilateral injection of Abeta42 peptide (2,2 nmol/10
      MUl) into the lateral ventricles. RA (50 mg/kg, daily) was administered orally by
      gavage for 14 days after intracerebroventricular injection. At the end of the
      experimental period, we recorded the auditory event related potentials (AERPs)
      and mismatch negativity (MMN) response to assess auditory functions followed by
      histological and biochemical analysis. Abeta42 injection led to a significant
      increase in the levels of thiobarbituric acid reactive substances (TBARS) and 4
      Hydroxy-2-nonenal (4-HNE) but decreased the activity of antioxidant enzymes (SOD,
      CAT, GSH-Px) and glutathione levels. Moreover, Abeta42 injection resulted in a
      reduction in the acetylcholine content and acetylcholine esterase activity. RA
      treatment prevented the observed alterations in the AbetaR group. Furthermore, RA
      attenuated the increased Abeta staining and astrocyte activation. We also found
      that Abeta42 injection decreased the MMN response and theta power/coherence of
      AERPs, suggesting an impairing effect on auditory discrimination and echoic
      memory processes. RA treatment reversed the Abeta42 related alterations in AERP
      parameters. In conclusion, our study demonstrates that RA prevented Abeta-induced
      antioxidant-oxidant imbalance and cholinergic damage, which may contribute to the
      improvement of neural network dynamics of auditory processes in this rat model.

PMID- 29655653
TI  - Increased risk of cardiovascular disease in women with prior gestational
      diabetes: A systematic review and meta-analysis.
AB  - This study aims to investigate the effect of gestational diabetes mellitus (GDM)
      on the long-term risk of cardiovascular disease (CVD). PubMed and other databases
      were searched up to August 31, 2017. Cohort studies evaluating risk of CVD
      postpartum in women with and without prior GDM were included. Random-effect model
      was used to estimate the pooled relative risk of CVD. Sensitivity and subgroup
      analyses were performed to check the consistency of the effect size and to
      explore sources of heterogeneity. Multivariable logistic regression was used to
      control for high heterogeneity. Seven cohort studies with 3,417,020 pregnant
      women including 14,146 incident CVD events were retrieved. In the pooled
      analysis, women with previous GDM had a higher risk of CVD than those without
      (RR: 1.74, 95%CI: 1.28-2.35, I2 = 95.7%). Four studies reported the event of
      coronary artery disease (CAD) and two studies reported stroke. The overall RR for
      CAD was 2.09 (95%CI: 1.56-2.80, I2 = 91.2%) and that for stroke was 1.25 (95%CI:
      1.07-1.48). In view of the high level of heterogeneity, adjustments were made for
      this, with the resulting adjusted OR for CVD and CAD being 1.95 (95%CI: 1.83
      2.08) and 1.59 (95%CI: 1.30-1.94). Women with prior GDM have increased risk of
      CVD.

PMID- 29655655
TI  - Hypothalamic peroxisome proliferator-activated receptor gamma regulates ghrelin
      production and food intake.
AB  - Peroxisome proliferator-activated receptor-gamma (PPARgamma) regulates fatty acid
      storage, glucose metabolism, and food intake. Ghrelin, a gastric hormone,
      provides a hunger signal to the central nervous system to stimulate appetite.
      However, the effects of PPARgamma on ghrelin production are still unclear. In the
      present study, the effects of PPARgamma on ghrelin production were examined in
      lean- or high-fat diet-induced obese (DIO) C57BL/6J mice and mHypoE-42 cells, a
      hypothalamic cell line. 3rd intracerebroventricular injection of adenoviral
      directed overexpression of PPARgamma (Ad-PPARgamma) reduced hypothalamic and
      plasma ghrelin, food intake in both lean C57BL/6J mice and diet-induced obese
      mice. These changes were associated with a significant increase in mechanistic
      target of rapamycin complex 1 (mTORC1) activity. Overexpression of PPARgamma
      enhanced mTORC1 signaling and suppressed ghrelin production in cultured mHypoE-42
      cells. Our results suggest that hypothalamic PPARgamma plays a vital role in
      ghrelin production and food intake in mice.

PMID- 29655654
TI  - Factorial structure and familial aggregation of the Hypomania Checklist-32 (HCL
      32): Results of the NIMH Family Study of Affective Spectrum Disorders.
AB  - BACKGROUND: There is substantial evidence that bipolar disorder (BD) manifests on
      a spectrum rather than as a categorical condition. Detection of people with
      subthreshold manifestations of BD is therefore important. The Hypomania Checklist
      32 (HCL-32) was developed as a tool to identify such people. PURPOSE: The aims of
      this paper were to: (1) investigate the factor structure of HCL-32; (2) determine
      whether the HCL-32 can discriminate between mood disorder subtypes; and (3)
      assess the familial aggregation and cross-aggregation of hypomanic symptoms
      assessed on the HCL with BD. PROCEDURES: Ninety-six probands recruited from the
      community and 154 of their adult first-degree relatives completed the HCL-32.
      Diagnosis was based on semi-structured interviews and family history reports.
      Explanatory factor analysis and mixed effects linear regression models were used.
      FINDINGS: A four-factor ("Activity/Increased energy,"
      "Distractibility/Irritability", "Novelty seeking/Disinhibition, "Substance use")
      solution fit the HCL-32, explaining 11.1% of the total variance. The
      Distractibility/Irritability score was elevated among those with BP-I and BP-II,
      compared to those with depression and no mood disorders. Higher HCL-32 scores
      were associated with increased risk of BD-I (OR = 1.22, 95%CI 1.14-1.30). The
      "Distractibility/Irritability" score was transmitted within families (beta =
      0.15, p = 0.040). However, there was no familial cross-aggregation between mood
      disorders and the 4 HCL factors. CONCLUSIONS: Our findings suggest that the HCL
      32 discriminates the mood disorder subtypes, is familial and may provide a
      dimensional index of propensity to BD. Future studies should explore the
      heritability of symptoms, rather than focusing on diagnoses.

PMID- 29655656
TI  - How Social, Cultural, and Economic Environments Shape Infant Feeding for Low
      Income Women: A Qualitative Study in North Carolina.
AB  - BACKGROUND: This study focuses on the cultural, social, and economic factors that
      shape infant feeding practices among low-income mothers. OBJECTIVE: The objective
      was to understand factors that inhibit or facilitate breastfeeding practices of
      low-income mothers, including how they are linked to broader social, cultural,
      and economic processes. DESIGN: In-depth qualitative interviews were conducted
      with women about their feeding practices and food environments, including their
      experiences with breastfeeding and formula feeding. PARTICIPANTS: The sample was
      comprised of 98 low-income mothers with at least one child between 2 and 9 years
      old at the time of interview. RESULTS: Sixteen mothers (16.7%) breastfed for 6
      months, and six (6.3%) were still breastfeeding at 12 months. Only 11 mothers
      (11.5%) exclusively breastfed for 6 months. Women reported several factors
      influencing infant feeding: interactions with medical providers, work
      environments, shared living spaces and family supports, and concerns about supply
      and production. CONCLUSIONS: This research highlights the complex interplay of
      economic and social barriers that shape how and what low-income women feed their
      infants. The study contributes to a better understanding of the social, cultural,
      and economic constraints faced by women in poverty. To improve breastfeeding
      rates among low-income women, it is important to examine the impacts of poverty
      and food insecurity on infant feeding practices.

PMID- 29655657
TI  - The Mindful Eating Behavior Scale: Development and Psychometric Properties in a
      Sample of Dutch Adults Aged 55 Years and Older.
AB  - BACKGROUND: Earlier scales on mindful eating do not measure mindful eating
      independent from emotional or external eating, or mindful eating in common
      situations. OBJECTIVE: The objective was to develop a new instrument to measure
      the attention element of mindful eating, the Mindful Eating Behavior Scale
      (MEBS), and to compute the internal structure, reliabilities, and convergent
      validity of this scale. DESIGN: A cross-sectional ancillary study within the
      Longitudinal Aging Study Amsterdam was conducted between fall 2014 and spring
      2015. PARTICIPANTS/SETTING: Participants were 1,227 Dutch adults aged 55 years
      and older from the Longitudinal Aging Study Amsterdam. MAIN OUTCOME MEASURE: A
      selection of 20 items from existing instruments was used to design an initial
      version of the MEBS. STATISTICAL ANALYSES PERFORMED: The internal structure of
      the MEBS was evaluated using an exploratory structural equation modeling approach
      on half of the sample and confirmatory factor analysis on the whole sample to
      develop the final version of the scale. The measurement invariance of the scores
      was tested with respect to sex, age, and body mass index. Reliabilities of
      subscales were determined with Cronbach's alpha. To test convergent validity, the
      scores of the new scale were correlated with theoretically relevant variables.
      RESULTS: Two items were deleted because of low item loadings and one item because
      of high correlated uniqueness. The final confirmatory factor analysis model with
      17 items and four domains (Focused Eating, Hunger and Satiety Cues, Eating with
      Awareness, and Eating without Distraction) showed good fit (comparative fit
      index=0.97, Tucker-Lewis index=0.96, and root mean square error of
      approximation=0.04). Measurement invariance was found for sex, age, and body mass
      index. Cronbach's alpha values were medium to high (.70 to .89). Most
      correlations were in the expected directions, which indicated good preliminary
      convergent validity. CONCLUSIONS: The MEBS was successfully developed consisting
      of 17 items and four domains. Because of low interfactor correlations, a total
      score combining the four domains should not be computed. The MEBS showed good
      internal consistency and preliminary convergent validity in a sample of Dutch
      adults aged 55 years and older.

PMID- 29655658
TI  - Elucidating the Mechanisms of Action of Saponin-Derived Adjuvants.
AB  - Numerous triterpenoid saponins are adjuvants that modify the activities of T
      cells and antigen-presenting cells, like dendritic cells (DCs). Saponins can
      induce either proinflammatory Th1/Th2 or sole anti-inflammatory Th2 immunities.
      Structure-activity relationships (SARs) have shown that imine-forming carbonyl
      groups are needed for T cell activation leading to induction of Th1/Th2
      immunities. While saponins having different triterpenoid aglycons and
      oligosaccharide chains can activate DCs to induce Th1/Th2 immunoresponses,
      fucopyranosyl residues from their oligosaccharides by binding to the DC-SIGN
      receptor can bias DCs toward a sole Th2 immunity. Here we discuss the mechanisms
      of action of these saponins in view of new information, which may serve as a
      basis to design improved adjuvants and related drugs.

PMID- 29655659
TI  - A V1143F mutation in the neuronal-enriched isoform 2 of the PMCA pump is linked
      with ataxia.
AB  - The fine regulation of intracellular calcium is fundamental for all eukaryotic
      cells. In neurons, Ca2+ oscillations govern the synaptic development, the release
      of neurotransmitters and the expression of several genes. Alterations of Ca2+
      homeostasis were found to play a pivotal role in neurodegenerative progression.
      The maintenance of proper Ca2+ signaling in neurons demands the continuous
      activity of Ca2+ pumps and exchangers to guarantee physiological cytosolic
      concentration of the cation. The plasma membrane Ca2+ATPases (PMCA pumps) play a
      key role in the regulation of Ca2+ handling in selected sub-plasma membrane
      microdomains. Among the four basic PMCA pump isoforms existing in mammals,
      isoforms 2 and 3 are particularly enriched in the nervous system. In humans,
      genetic mutations in the PMCA2 gene in association with cadherin 23 mutations
      have been linked to hearing loss phenotypes, while those occurring in the PMCA3
      gene were associated with X-linked congenital cerebellar ataxias. Here we
      describe a novel missense mutation (V1143F) in the calmodulin binding domain (CaM
      BD) of the PMCA2 protein. The mutant pump was present in a patient showing
      congenital cerebellar ataxia but no overt signs of deafness, in line with the
      absence of mutations in the cadherin 23 gene. Biochemical and molecular dynamics
      studies on the mutated PMCA2 have revealed that the V1143F substitution alters
      the binding of calmodulin to the CaM-BD leading to impaired Ca2+ ejection.

PMID- 29655660
TI  - Use of the MatrixWAVETM system with dentures to establish maxillomandibular
      fixation in edentulous patients.
AB  - Various methods have been described to establish maxillomandibular fixation in
      the treatment of fractures of atrophic, edentulous mandibles. We used the Synthes
      MatrixWAVETM system (DePuy Synthes) in combination with dentures in two patients
      with fractured, edentulous, atrophic mandibles. Fixation was maintained for
      fractures that were not amenable to, or did not require, open reduction and
      internal fixation, and the mandibles were both well-healed and had good function
      at the end of treatment.

PMID- 29655661
TI  - Oral rehabilitation of patients after maxillectomy. A systematic review.
AB  - Patients who have maxillectomy can be rehabilitated with reconstructive surgery
      or obturator prostheses with or without osseointegratable implants. To identify
      studies on possible treatments in this group, we systematically searched the
      Scopus, Embase, PubMed/Medline, and Cochrane databases to collect data on
      patients' characteristics, radiotherapy, and results related to speech,
      swallowing, mastication or diet, chewing, aesthetics, and quality of life. Of the
      1376 papers found, six were included, and one other was included after an
      additional search of references. A total of 252 patients were included, and of
      them, 86 had reconstructive surgery, 91 were treated with obturator prostheses,
      39 had reconstructive surgery or obturator prostheses associated with implants,
      and 36 had reconstruction plus an obturator prosthesis. Data on radiotherapy were
      incomplete. There is a lack of consensus about the indication for rehabilitation,
      as the treatment must be based on the individual characteristics of each patient.

PMID- 29655663
TI  - Announcements for this section should be submitted in the correct format at least
      3 months before the required date of publication. This list is provided as a
      service to readers; inclusion does not imply endorsement by the Hepatobiliary &
      Pancreatic Diseases International.

PMID- 29655662
TI  - Evaluation of low-intensity anti-coagulation with a fully magnetically levitated
      centrifugal-flow circulatory pump-the MAGENTUM 1 study.
AB  - BACKGROUND: The HeartMate 3 left ventricular assist system is engineered to avoid
      pump thrombosis, yet bleeding complications persist. We investigated the safety
      of low-intensity anti-coagulation in patients with the HeartMate 3. METHODS: The
      Minimal AnticoaGulation EvaluatioNTo aUgment heMocompatibility (MAGENTUM 1) pilot
      study is a prospective, single-arm study of low-intensity warfarin anti
      coagulation in patients implanted with the HeartMate 3 pump. After standard
      warfarin anti-coagulation (international normalized ratio [INR] 2.0 to 3.0) and
      aspirin for 6 weeks post-implant, patients were transitioned to a lower INR
      target range of 1.5 to 1.9. The primary end-point was a composite of survival
      free of pump thrombosis, disabling stroke (modified Rankin score [MRS] >3), or
      major bleeding (excluding peri-operative bleeding) with at least 6-month post
      implant follow-up. Time in therapeutic range (TTR) was measured to assess anti
      coagulation target efficacy using the Rosendaal method. A safety algorithm to
      monitor for signs of pump thrombosis was developed and implemented. RESULTS: We
      enrolled 15 patients (mean age 57.3 +/- 13.3 years), 13 men with advanced heart
      failure (67% with INTERMACS Profiles 2 or 3), irrespective of therapeutic goal of
      bridge-to-transplant or destination therapy. The primary end-point was met in 14
      of 15 (93 +/- 6%) patients; 1 patient developed recurrent gastrointestinal
      bleeding. The TTR during the reduced anti-coagulation phase (6 weeks to 6 months)
      was 75.3 +/- 8.6%. No thrombotic events occurred. CONCLUSIONS: This pilot study
      suggests low-intensity anti-coagulation targeting an INR between 1.5 and 1.9 is
      achievable and safe with the HeartMate 3 cardiac pump in the short-term phase, 6
      months post-implant. A large-scale trial is now warranted.

PMID- 29655664
TI  - A retrospective investigation of abdominal visceral fat, body mass index (BMI),
      and active smoking as risk factors for donor site wound healing complications
      after free DIEP flap breast reconstructions.
AB  - BACKGROUND: The deep inferior epigastric artery perforator (DIEP) flap is one of
      the most common techniques for breast reconstruction. Body mass index (BMI) is
      considered as an important predictor of donor site healing complications such as
      wound dehiscence. The use of computed tomography (CT) proved to be a precise and
      objective method to assess visceral adipose tissue. It remains unclear whether
      quantification of visceral fat provides more accurate predictions of abdominal
      wound healing complications than BMI. PATIENTS AND METHODS: A total of 97
      patients with DIEP flap were retrospectively evaluated. Patients' abdominal
      visceral fat (AVF) was quantified on CT angiography (CTA). The patients were
      postoperatively assessed for abdominal wound healing complications. We analyzed
      for the correlations between AVF, BMI, and dehiscence and established a logistic
      regression model to assess the potential high-profile predictors in anatomic and
      patient characteristics such as weight, smoking, and diabetes. RESULTS: We
      included 97 patients, and of them, 24 patients (24.7%) had some degree of
      abdominal dehiscence. No significant differences were observed between the
      dehiscence group and the non-dehiscence group, except for smoking (p = 0.002). We
      found a significant correlation between AVF and BMI (R = 0.282, p = 0.005), but
      neither was significant in predicting donor site dehiscence. Smoking greatly
      increased the likelihood of developing wound dehiscence (OR = 11.4, p = < 0.001).
      CONCLUSIONS: AVF and BMI were not significant predictors of abdominal wound
      healing complications after DIEP flap reconstruction. This study established
      active smoking (OR = 11.4, p = < 0.001) as the significant risk factor that
      contributed to the development of abdominal wound dehiscence in patients with
      DIEP.

PMID- 29655665
TI  - Descending genicular artery. Branching patterns and measuring parameters: A
      systematic review and meta-analysis of several anatomical studies.
AB  - BACKGROUND: The medial femoral condyle (MFC) flap is based on the descending
      genicular artery (DGA), which is a vessel with different variations in its course
      and branching patterns. Many studies have dealt with the vascular anatomy of the
      MFC. However, the results of the investigations differ markedly. METHODS: The
      authors performed a systematic literature search in MEDLINE for articles
      published until May 2017 on the vascular anatomy of the DGA. After the screening,
      23 relevant studies with a similar topic were included into this comprehensive
      analysis. RESULTS: The systematic review examined the lengths and diameters of
      the individual arteries with regard to the vascularized bone flap of the MFC. The
      DGA is present in 94% of cases with an average length of 1.8 cm. In 63% of the
      investigated cases, the DGA divides into three terminal branches. The articular
      branch has an average length of 7.7 cm, the saphenous branch has a length of 10.7
      cm, and the muscular branch has a length of 3.2 cm. CONCLUSION: To ensure a
      secured survival of this free flap, a detailed understanding of the convoluted
      vascular anatomy above the MFC is necessary. We recommend the Dubois
      classification for a systematic classification of the anatomical patterns of the
      DGA.We present a summary of all anatomical studies dealing with the vascular
      supply to the MFC and the DGA to date.

PMID- 29655666
TI  - Environmental considerations in the selection of isolation gowns: A life cycle
      assessment of reusable and disposable alternatives.
AB  - BACKGROUND: Isolation gowns serve a critical role in infection control by
      protecting healthcare workers, visitors, and patients from the transfer of
      microorganisms and body fluids. The decision of whether to use a reusable or
      disposable garment system is a selection process based on factors including
      sustainability, barrier effectiveness, cost, and comfort. Environmental
      sustainability is increasingly being used in the decision-making process. Life
      cycle assessment is the most comprehensive and widely used tool used to evaluate
      environmental performance. METHODS: The environmental impacts of market
      representative reusable and disposable isolation gown systems were compared using
      standard life cycle assessment procedures. The basis of comparison was 1,000
      isolation gown uses in a healthcare setting. The scope included the manufacture,
      use, and end-of-life stages of the gown systems. RESULTS: At the healthcare
      facility, compared to the disposable gown system, the reusable gown system showed
      a 28% reduction in energy consumption, a 30% reduction in greenhouse gas
      emissions, a 41% reduction in blue water consumption, and a 93% reduction in
      solid waste generation. CONCLUSIONS: Selecting reusable garment systems may
      result in significant environmental benefits compared to selecting disposable
      garment systems. By selecting reusable isolation gowns, healthcare facilities can
      add these quantitative benefits directly to their sustainability scorecards.

PMID- 29655667
TI  - Estimating the attributable costs of hospital-acquired infections requires a
      distinct categorization of cases based on time of infection.

PMID- 29655668
TI  - Nonventilator hospital-acquired pneumonia: Where do we go from here?

PMID- 29655669
TI  - Rate of contamination of hospital privacy curtains in a burns/plastic ward: A
      longitudinal study.
AB  - BACKGROUND: Since hospital patient privacy curtains can harbor bacteria, are high
      touch surfaces, and are cleaned infrequently, they may be involved in pathogen
      transmission. The aim of this longitudinal prospective study was to understand
      curtain contamination to inform curtain hygiene protocols, thereby minimizing the
      role of curtains in pathogen transmission. METHODS: Over 21 days, cultures of 10
      freshly laundered curtains (8 test curtains surrounding patient beds and 2
      controls in an unoccupied staff room) were taken in the Regional Burns/Plastics
      Unit. Contact plates were used to sample the curtains near the edge hem where
      they are most frequently touched. Microbial contamination and the presence of
      methicillin-resistant Staphylococcus aureus (MRSA) were determined. RESULTS: By
      day 3, test curtains showed increased microbial contamination (mean colony
      forming units [CFU]/cm2 = 1.17) compared to control curtains (mean CFU/cm2 =
      0.19). Test curtains became increasingly contaminated over time, with mean
      CFU/cm2 for days 17 and 21 of 1.86 and 5.11, respectively. By day 10, 1/8 test
      curtains tested positive for MRSA, and 5/8 were positive by day 14. CONCLUSIONS:
      Patient privacy curtains became progressively contaminated with bacteria,
      including MRSA. Between days 10 and 14 after being hung, curtains showed
      increased MRSA positivity. This may represent an opportune time to intervene,
      either by cleaning or replacing the curtains.

PMID- 29655670
TI  - Wettability of hands during 15-second and 30-second handrub time intervals: A
      prospective, randomized crossover study.
AB  - OBJECTIVE: At present, the shortest recommended application time of alcoholic
      handrubs is an application interval of 30 seconds. However, application times
      shorter than 30 seconds are regularly practiced. Therefore, the aim of this study
      was to investigate whether a 15-second application time achieves a comparable
      wettability of hands to a 30-second handrub application. SETTING: The wettability
      of 20 healthy volunteers' hands was compared after 15 seconds or 30 seconds of
      application time of an ultraviolet-light-active handrub, both before and after
      training in the application technique. Images of the ventral side and dorsal side
      of the hands were evaluated by computer software. Both groups' outcomes were
      analyzed with regard to the spread of the handrub on hands. RESULTS: There was no
      difference between the wetted areas of the hands after 15 seconds or 30 seconds
      of handrub application. A significant difference was observed between the wetted
      areas of hands in trained volunteers compared with untrained volunteers,
      irrespective of application time. CONCLUSION: Based on our results, a 15-second
      application time is equal to 30-second application time in terms of wettability
      of hands. The improvement of wettability after training underlines the necessity
      to instruct new and untrained health care workers in hand antisepsis. Using
      fluorescent handrubs may be a feasible method to control and retrain hand hygiene
      techniques of long-time employees.

PMID- 29655671
TI  - Overreporting healthcare-associated C. difficile: A comparison of NHSN LabID with
      clinical surveillance definitions in the era of molecular testing.
AB  - BACKGROUND: Clostridium difficile infection (CDI) is the most common healthcare
      associated gastrointestinal infection. Hospitals are required to report cases of
      healthcare facility-onset CDI (HO-CDI) using the National Healthcare Safety
      Network's CDI laboratory-identified (LabID) event definition. The aim of this
      study was to determine the extent of potential over-reporting due to the
      exclusion of important clinical data within LabID reporting definitions. METHODS:
      In 2015, retrospective chart review was performed on 212 HO-CDI cases reported
      from a large urban medical center. Cases had positive polymerase chain reaction
      test for the C. difficile toxin B gene from an unformed stool specimen collected
      >3 days after admission and >8 weeks after most recent LabID event. Cases were
      categorized into "clinical surveillance" groups: community-acquired infection,
      recurrence/relapse, asymptomatic colonization, colonization with self-limited
      symptoms, possible HO-CDI, and probable HO-CDI. RESULTS: Of the infections, 13.6%
      were community acquired, 2.8% were recurrent/relapse, 1.9% were asymptomatic
      colonization, 18.4% were symptomatic colonization, 38.7% were possible HO-CDI,
      and 24.5% were probable HO-CDI. Within 24 hours of testing, 34.1% of patients had
      received a stool softener and/or laxative. CONCLUSIONS: Laxative use and failure
      to identify community-onset infection may contribute to misclassification of HO
      CDI. Only 62% of reported cases met clinical surveillance criteria.

PMID- 29655672
TI  - Effect of pulsed xenon ultraviolet room disinfection devices on microbial counts
      for methicillin-resistant Staphylococcus aureus and aerobic bacterial colonies.
AB  - BACKGROUND: Inadequate environmental disinfection represents a serious risk for
      health care-associated infections. Technologic advancements in disinfection
      practices, including no-touch devices, offer significant promise to improve
      infection control. We evaluated one such device, portable pulsed xenon
      ultraviolet (PX-UV) units, on microbial burden during an implementation trial
      across 4 Veterans Affairs hospitals. METHODS: Environmental samples were
      collected before and after terminal room cleaning: 2 facilities incorporated PX
      UV disinfection into their cleaning protocols and 2 practiced manual disinfection
      only. Specimens from 5 high-touch surfaces were collected from rooms harboring
      methicillin-resistant Staphylococcus aureus (MRSA) or aerobic bacteria colonies
      (ABC). Unadjusted pre-post count reductions and negative binomial regression
      modeled PX-UV versus manual cleaning alone. RESULTS: Seventy samples were
      collected. Overall, PX-UV reduced MRSA and ABC counts by 75.3% and 84.1%,
      respectively, versus only 25%-30% at control sites. Adjusting for baseline
      counts, manually cleaned rooms had significantly higher residual levels than PX
      UV sites. Combined analyses revealed an incident rate ratio of 5.32 (P = .0024),
      with bedrails, tray tables, and toilet handrails also showing statistically
      superior PX-UV disinfection. CONCLUSIONS: This multicenter study demonstrates
      significantly reduced disinfection across several common pathogens in facilities
      using PX-UV devices. Clinical impact of laboratory reductions on infection rates
      was not assessed, representing a critical future research question. However, such
      approaches to routine cleaning suggest a practical strategy when integrated into
      daily hospital operations.

PMID- 29655674
TI  - Analysis of microRNA expression in the thymus of Myasthenia Gravis patients opens
      new research avenues.
AB  - In early-onset Myasthenia Gravis (MG) with anti-acetylcholine receptor
      antibodies, thymic abnormalities associated with ectopic germinal centers are
      frequent. miRNAs by acting as post-transcriptional regulators are involved in
      autoimmunity. To investigate the implication of miRNAs in thymic changes
      associated with early-onset MG, we performed a miRnome study and data were
      analyzed with different approaches. miRNAs of interest were further investigated
      by RT-PCR and transfection experiments for functional tests. First, analyzing
      specific dysregulated miRNAs, we focused our attention on miR-7-5p and miR-125a
      5p, and confirmed by RT-PCR their respective down- and up-regulation in MG
      thymuses. miR-7 was the most down-regulated thymic miRNA in MG and we observed an
      inverse correlation between its expression and CCL21 mRNA expression. We next
      showed that miR-7 down-regulation was due to thymic epithelial cells and by
      transfecting these cells with miR-7, we demonstrated that it controlled CCL21
      release. As CCL21 is essential for germinal center development, we suggested that
      miR-7 could be involved in thymic changes associated with MG. miR-125a was up
      regulated in MG thymuses and is of great interest as it is known to regulate
      FoxP3 expression, and to modulate the different inflammatory signaling pathways.
      Thanks to this thymic miRnome study, we also showed the specific dysregulation of
      miRNA clusters. In particular, we observed that miRNAs localized at the extremity
      of the X chromosome were down-regulated. This effect seemed linked to their close
      localization to the fragile X mental retardation 1 gene (FMR1) and the DNA
      methylation status. Altogether, this miRnome analysis demonstrated that specific
      thymic miRNAs can be associated with MG and provides novel insights into the
      pathogenesis of MG.

PMID- 29655673
TI  - Macrophages: The Road Less Traveled, Changing Anticancer Therapy.
AB  - Macrophages are present in all vertebrate tissues and have emerged as
      multifarious cells with complex roles in development, tissue homeostasis, and
      disease. Macrophages are a major constituent of the tumor microenvironment, where
      they either promote or inhibit tumorigenesis and metastasis depending on their
      state. Successful preclinical strategies to target macrophages for anticancer
      therapy are now being evaluated in the clinic and provide proof of concept that
      targeting macrophages may enhance current therapies; however, clinical success
      has been limited. This review discusses the promise of targeting macrophages for
      anticancer therapy, yet highlights how much is unknown regarding their ontogeny,
      regulation, and tissue-specific diversity. Further work might identify subsets of
      macrophages within different tissues, which could reveal novel therapeutic
      opportunities for anticancer therapy.

PMID- 29655675
TI  - Eupatilin suppresses the allergic inflammatory response in vitro and in vivo.
AB  - INTRODUCTION: Eupatilin, a pharmacologically active ingredient found in Artemisia
      asiatica, has been reported to have anti-oxidative, anti-inflammatory, and anti
      apoptotic activities. However, molecular mechanisms underlying its anti-allergic
      properties are not yet clear. In this study, we investigated the effects of
      eupatilin on allergic inflammation in phorbol 12-myristate 13-acetate plus
      calcium ionophore A23187 (PMACI)-stimulated human mast cells and a compound 48/80
      induced anaphylactic shock model. METHODS: Cytokine assays, histamine assays,
      quantitative real-time polymerase chain reaction analysis, western blot analysis
      and compound 48/80-induced anaphylactic shock model were used in this study.
      RESULTS: Eupatilin significantly suppresses the expression and production of pro
      inflammatory cytokines, such as interleukin (IL)-1beta, tumor necrosis factor
      (TNF)-alpha, and IL-6 in vitro and in vivo. In addition, eupatilin inhibits
      nuclear factor kappa B (NF-kappaB) activation by regulating the phosphorylation
      and degradation of IkappaBalpha via the Akt/IKK(alpha/beta) pathway. Eupatilin
      treatment also attenuates the phosphorylation of p38, ERK, and JNK MAPKs.
      Furthermore, eupatilin blocked anaphylactic shock and decreased the release of
      histamine. CONCLUSIONS: Anti-allergic inflammation may involve the expression and
      production of regulating pro-inflammatory cytokines via Akt/IKK(alpha/beta) and
      MAPK activation of NF-kappaB. On the basis of these data, eupatilin is a
      potential candidate for the treatment of allergic diseases.

PMID- 29655676
TI  - Protective effect of Juglans regia L. against ultraviolet B radiation induced
      inflammatory responses in human epidermal keratinocytes.
AB  - BACKGROUND: Juglans regia L. has a history of traditional medicinal use for the
      treatment of various maladies and have been documented with significant
      antioxidant and antiinflammatory properties. Although all parts of the plant are
      medicinally important, but male the flower of the plant has not been yet
      investigated against the photo-damage. PURPOSE: The present study, we sought to
      determine the photoprotective effect of the male flower of J. regia L. against
      ultraviolet-B radiation-induced inflammatory responses in human skin cells.
      METHODS: The profile of pharmacological active compounds present in the male
      flower of J. regia was analyzed by GC-MS. Then, the antioxidant property of
      methanolic extract of J. regia (MEJR) was analyzed by in vitro free radical
      scavenging assays. Further, we analyzed the sun protection factor of this extract
      by spectrophotometry. Moreover, we investigated the photoprotective effect of
      MEJR against UVB induced inflammatory signaling in human epidermal cells. Human
      skin epidermal keratinocytes (HaCaT) were pretreated with the MEJR (80 ug/ml), 30
      min prior to UVB-irradiation at a dose of 20 mJ/cm2 and were investigated for
      lipid peroxidation, enzymatic antioxidants activity, apoptosis and inflammatory
      markers expression level. RESULTS: The GC-MS results showed the presence of good
      amount of pharmacologically active compounds in the MEJR. We observed that the
      MEJR possess significant free radical scavenging activity and it was comparable
      with standard antioxidants. Further, the MEJR exhibits 8.8 sun-protection-factor
      (SPF) value. Pretreatment with MEJR, 30 min prior to UVB-irradiation, prevented
      ROS generation, lipid peroxidation and restored the activity of antioxidant
      status in HaCaT cells. Moreover, MEJR pretreatment significantly prevented UVB
      activated inflammatory markers like TNF-alpha, IL-1, IL-6, NF-kappaB, COX-2 in
      HaCaT. CONCLUSION: The present findings suggest that MEJR exhibit photoprotective
      effects and hence it may be useful for the treatment of inflammation related
      responses. The pharmacological mechanism of MEJR partly associated with its UV
      absorbance, modulation of inflammatory signaling as well as due to its free
      radical scavenging capability.

PMID- 29655677
TI  - An in vitro and in vivo study of a 4-herb formula on the management of diet
      induced metabolic syndrome.
AB  - BACKGROUND: Metabolic syndrome is the cluster of risk factors that leads to
      increased episodes of cardiovascular disease (CVD). These risk factors include
      but are not limited to obesity, non-alcoholic fatty liver (NAFLD), dyslipidemia,
      and type 2 diabetes. Since the pathogenesis of metabolic syndrome has multiple
      metabolic origins, there is no single treatment for it. Pharmacological
      approaches consist of separate drugs which target at individual risk factors
      which pose various side effects. Functional foods or nutraceuticals which have
      potentially important anti-obesity properties have thus attracted great
      attention. Schisandrae Fructus is a Chinese herb traditionally used as a liver
      tonic. Silymarin, an extract of the milk thistle (Silybum marianum), is a dietary
      supplement that is widely used in western society for the prevention and
      treatment of liver problems. Crataegus Fructus (hawthorn) is traditionally used
      to promote digestion and dissipate food stagnation. Momordica charantia (bitter
      melon) is traditionally used for treatment of diabetes in Ayurvedic Medicine.
      HYPOTHESIS/PURPOSE: We aimed to develop a multi-targeted herbal formula to target
      on the multiple risk factors of metabolic syndrome using individual herbs. This
      proposed herbal formula include sylimarin and Schisandrae Fructus, for NAFLD;
      Crataegus Fructus for obesity and hyperlipidemia; and Momordica charantia for
      hyperglycemia. STUDY DESIGN AND METHODS: For in vitro study, we carried out
      insulin-induced 3T3-L1 adipocytes differentiation and fluorescent tagged
      cholesterol-treated Caco-2 cell assay to study for adipogenesis and cholesterol
      uptake into Caco-2 cells, respectively. Oleic acid-induced HepG2 cell assay was
      used to study for oleic acid-induced fatty liver, and brush border membrane
      vesicles (BBMV) assay was used to study for glucose uptake from the gut. For in
      vivo study, we performed an 8-week and a 12-week treatment studies, with each
      study comprising of 4 groups of C57Bl/6 male mice given: (i) Normal-chow diet;
      (ii)-(iv) High-fat diet (contains 21% fat and 0.15% cholesterol). After the
      initial 8 weeks of normal chow or high-fat diet feeding to induce obesity,
      animals were given: (i) Normal-chow diet; (ii) High-fat diet; (iii) High-fat diet
      + 2% herbal formula; or (iv) High-fat diet + 4% herbal formula as treatment for
      another 8 weeks or 12 weeks. RESULTS: Our in vitro results suggested Crataegus
      Fructus aqueous extract exerted potent inhibitory effects on 3T3-L1 preadipocytes
      differentiation and cholesterol uptake into Caco-2 cells. Schisandrae Fructus
      aqueous extract and milk thistle exerted inhibitory effects on oleic acid-induced
      fatty liver in HepG2 cells. Momordica charantia extract on the other hand,
      exerted significant inhibitory effect on glucose uptake into BBMV. Our in vivo
      results showed that our herbal formula exhibited a trend to reduce diet-induced
      increase in body weight and fat pad mass (epididymal, perirenal and inguinal
      fat); and significantly reduced diet-induced increase in liver weight, liver
      lipid, and plasma lipid dose-dependently. Besides, high-fat diet induced a
      significant reduction in adiponectin level which was significantly improved by
      herbal formula supplementation at 4%. There was however no significant effect of
      the herbal formula on diet-induced increase in plasma glucose or insulin levels
      at either dose. Herbal formula also significantly reduced diet-induced
      inflammation in the liver at both doses. CONCLUSIONS: Taken together, these data
      suggested the potential of our novel multi-targeted herbal formula to be used as
      a therapeutic agent for diet-induced metabolic syndrome, with special emphasis on
      NAFLD.

PMID- 29655678
TI  - Anti-inflammatory and antioxidant activities of naringin isolated from Carissa
      carandas L.: In vitro and in vivo evidence.
AB  - BACKGROUND: Carissa carandas L. is known in folk medicine for its anti
      inflammatory and hepatoprotective activities. Meanwhile it is an evergreen shrub
      that constitutes a continuous source of leaves throughout the year.
      HYPOTHESIS/PURPOSE: The leaves of Carissa carandas L. may be rich in compounds
      that can be used as safe anti-inflammatory and antioxidant remedies. The combined
      antioxidant and anti-inflammatory activities provoked the study of the
      hepatoprotective effects. STUDY DESIGN: To isolate major constituents from the
      leaves of Carissa carandas L. and test their anti-inflammatory and antioxidant
      activities in-vivo and in-vitro. METHODS: The leaves of Carissa carandas L. were
      extracted with 80% MeOH and then defatted with CHCl3 to yield Carissa carandas
      defatted extract (CCDE). The extract was chemoprofiled using UPLC-MS/MS to stand
      for major constituents, then subjected to different chromatographic separation
      steps and naringin (NG) was isolated in a high yield. The anti-inflammatory
      activity of NG was investigated in-vivo by carrageenan induced hind rat paw edema
      model at two dose levels (50 and 25 mg/kg). The anti-inflammatory activity was
      also evaluated in-vitro by measuring its inhibitory effect on LPS induced release
      of NO from RAW 264.7 macrophages. The antioxidant activity was evaluated by
      superoxide and DPPH radical scavenging ability. The safety of NG was tested
      against primary rat hepatocytes. The hepatoprotective effect of CCDE was
      evaluated by detecting its effects on serum liver function markers and liver cell
      oxidative stress markers. RESULTS: NG exhibited potent inhibition of inflammation
      as compared to indomethacin (20 mg/kg). NG inhibited LPS induced release of NO
      from macrophages (IC50, 6.4 MUM). NG showed significant antioxidant activity as
      it scavenged the superoxide radical (EC90, 10.95 MUM) and DPPH radical (EC50,
      11.2 MUM). CCDE inhibited the elevation of the serum liver marker enzymes and
      increased GSH and decreased MDA contents in the liver homogenate. Liver
      histopathology supported the biochemical findings. CONCLUSION: C. carandas has
      potent anti-inflammatory, antioxidant and hepatoprotective activities.

PMID- 29655679
TI  - The extract of Polygoni Cuspidati Rhizoma et Radix suppresses the vascular
      endothelial growth factor-induced angiogenesis.
AB  - BACKGROUND: Polygoni Cuspidati Rhizoma et Radix (PCRR; the root and rhizome of
      Polygonum cuspidatum Sieb. et Zucc) is a traditional Chinese medicine for the
      treatment of inflammation, hyperlipemia, favus, jaundice and scald.
      HYPOTHESIS/PURPOSE: The extract of PCRR inhibits vascular endothelial growth
      factor (VEGF)-induced angiogenesis. The hypothesis is supported by analysis of
      PCRR extract and investigation of pharmacological role and signaling mechanism of
      PCRR extract in regulating angiogenic responses. STUDY DESIGN: The PCRR ethanolic
      extract was examined for its inhibitory effects on angiogenesis based on VEGF
      treated human umbilical vein endothelial cells and in zebrafish model METHODS:
      The effects and signaling mechanism of a standardized ethanolic extract of PCRR
      were tested on cell proliferation, migration and tube formation in VEGF-treated
      human umbilical vein endothelial cells, and which was further validated in
      zebrafish embryo model. RESULTS: The treatment of PCRR extract in cultured
      endothelial cells inhibited VEGF-induced cell proliferation, cell migration and
      tube formation in a dose-dependent manner and also suppressed the formation of
      sub-intestinal vessels in zebrafish embryos. Moreover, the applied PCRR extract
      suppressed VEGF-induced phosphorylations of VEGF receptor 2 (VEGFR2) and JNK.
      Thus, the site of effect triggered by PCRR was proposed to be mediated by VEGFR2.
      To further support this notion, the phosphorylations of Erk, Akt and eNOS,
      induced by VEGF, were markedly reduced under the challenge of PCRR extract: the
      reductions were subsequently further decreased in the present of inhibitors of
      Erk, Akt and eNOS. In parallel, the formation of ROS induced by VEGF in cultured
      endothelial cells was markedly reduced in the present of PCRR extract.
      CONCLUSION: Collectively, our studies demonstrated the pharmacological role and
      signaling mechanism of PCRR in regulation of angiogenic responses, which
      supported further evaluation and development of PCRR as a potential therapeutic
      agent for the treatment and prevention of diseases related with angiogenesis.

PMID- 29655680
TI  - Panduratin A induces protective autophagy in melanoma via the AMPK and mTOR
      pathway.
AB  - BACKGROUND: Targeting autophagy is emerging as a promising strategy in cancer
      therapeutics in recent years. Autophagy can be modulated to drive cancer cell
      deaths that are notoriously resistant to apoptotic-inducing drugs. In addition,
      autophagy has been implicated as a prosurvival mechanism in mediating cancer
      chemoresistance. Our previous study has demonstrated that Panduratin A (PA), a
      plant-derived active compound exploits ER-stress-mediated apoptosis as its
      cytotoxic mechanism on melanoma. PURPOSE: Our previous proteomics analysis
      revealed that treatment with PA resulted in the upregulation of an autophagy
      marker, LC3B in melanoma cells. Therefore, the present study sought to
      investigate the role of PA-induced autophagy in melanoma cells. METHODS:
      Transmission electron microscopy was performed for examination of autophagic
      ultra-structures in PA-treated A375 cells. Cytoplasmic LC3B and p62/SQSMT1
      punctate structures were detected using immunofluorescene staining. Expression
      levels of LC3B II, p62/SQSMT1, ATG 12, Beclin 1, phospho S6 (ser235/236), phospho
      AMPK (Thr172) and cleaved PARP were evaluated by western blotting. RESULTS:
      Autophagosomes, autolysosomes and punctuates of LC3 proteins could be observed in
      PA-treated A375 cells. PA-induced autophagy in A375 melanoma cells was found to
      be mediated through the inhibition of mTOR signaling and activation of AMPK
      pathway. Furthermore, we showed that PA-induced apoptosis was increased in the
      presence of an autophagy inhibitor, signifying the cytoprotective effect of PA
      induced autophagy in melanoma cells. CONCLUSION: Taken together, results from the
      present study suggest that the inhibition of autophagy by targeting mTOR and AMPK
      could potentiate the cytotoxicity effects of PA on melanoma cells.

PMID- 29655681
TI  - Anti-inflammatory activity of Khayandirobilide A from Khaya senegalensis via NF
      kappaB, AP-1 and p38 MAPK/Nrf2/HO-1 signaling pathways in lipopolysaccharide
      stimulated RAW 264.7 and BV-2 cells.
AB  - BACKGROUND: Immunocytes-involved inflammation is considered to modulate the
      damage in various diseases. Herein, novel therapeutics suppressing over
      activation of immunocytes could prove an effective strategy to prevent
      inflammation-related diseases. PURPOSE: The objective of this study is to
      evaluate the anti-inflammatory activity of Khayandirobilide A (KLA), a new
      andirobin-type limonoid with modified furan ring isolated from the Khaya
      senegalensis (Desr.) A. Juss., and to explore its potential underlying mechanisms
      in LPS-stimulated inflammatory models. METHODS: The structure of KLA was
      elucidated on the basis of 1D- and 2D-NMR spectroscopic data as well as HR-ESI
      MS. As for its anti-inflammatory effect, the production of pro-inflammatory
      mediators and cytokines in LPS-stimulated RAW 264.7 and BV-2 cells were measured
      by Griess reagent, ELISA and qRT-PCR. The relevant proteins including nuclear
      factor kappaB (NF-kappaB), p-AKT, p-p38 and Nrf2/HO-1 were investigated by
      western blot. Nuclear localisations of NF-kappaB, activator protein-1 (AP-1) and
      Nrf2 were also examined by western blot and immunofluorescence. RESULTS: KLA
      could inhibit the production of LPS-induced NO with IC50 values of 5.04 +/- 0.14
      uM and 4.97 +/- 0.5 uM in RAW 264.7 and BV-2 cells, respectively. KLA also
      attenuated interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS) and
      cyclooxygenase-2 (COX-2) at the protein and mRNA levels. Further mechanistic
      studies demonstrated the activation of NF-kappaB and AP-1 were reduced by KLA.
      Moreover, KLA elevated expression of heme oxygenase-1(HO-1) via inducing Keap1
      autophagic degradation and promoting Nrf2 nuclear translocation. Despite KLA
      induced the phosphorylation of mitogen-activated protein kinases (MAPKs) family,
      inhibiting the phosphorylation of p38 by its specific inhibitor SB203580
      attenuated the degradation of KLA-induced Keap1, and then reduced KLA-induced
      Nrf2 nuclear translocation and HO-1 expression. Furthermore, SB203580, Brusatol
      (a Nrf2 specific inhibitor) and ZnPP (a HO-1 specific inhibitor) could partly
      reverse the suppressive effects of KLA on LPS-induced NO production and mRNA
      levels of pro-inflammatory genes. CONCLUSION: These data displayed that KLA
      possessed anti-inflammatory activity, which was attributed to inhibit the release
      of LPS-stimulated inflammatory mediators via suppressing the activation of NF
      kappaB, AP-1, and upregulating the induction of p38 MAPK/Nrf2-mediated HO-1.

PMID- 29655682
TI  - Pristimerin, a naturally occurring triterpenoid, attenuates tumorigenesis in
      experimental colitis-associated colon cancer.
AB  - BACKGROUND: Pristimerin is a quinonemethide triterpenoid with anti-cancer, anti
      angiogenic, anti-inflammatory and anti-protozoal activity. However, the
      therapeutic role of pristimerin in colitis-associated colorectal carcinogenesis
      is unknown. PURPOSE: We sought to examine the therapeutic effects of pristimerin
      on colitis-associated colon cancer induced in mice using azoxymethane
      (AOM)/dextran sulfate sodium (DSS). The goal was to identify the potential
      mechanism of action underlying the pharmacological activity of pristimerin.
      METHODS: BALB/c mice were injected with AOM and administered 2% DSS in drinking
      water. The mice were fed with a diet supplemented with pristimerin (1 to 5 ppm),
      and colonic tissue was collected at 64 days. The inflammatory status of the colon
      was assessed by determining the levels of cyclooxygenase-2, inducible nitric
      oxide synthase and pro-inflammatory cytokines using Western blotting,
      immunohistochemistry and real-time RT-PCR analyses. Markers of proliferation
      (proliferating cell nuclear antigen) and apoptosis (TUNEL) were identified in the
      colon tissues immunohistochemically. The levels of cell cycle-, apoptosis-, and
      signaling-related proteins were detected by Western blot in colon tissues.
      RESULTS: Administration of pristimerin significantly reduced the formation of
      colonic tumors. Western blot and immunohistological analyses revealed that
      dietary pristimerin markedly reduced NF-kappaB-positive cells and levels of
      inflammation-related proteins in colon tissue. Pristimerin also reduced cell
      proliferation, induced apoptosis, and decreased the phosphorylation of AKT and
      FOXO3a in colon tissue. CONCLUSION: Pristimerin administration decreased
      inflammation and proliferation induced by AOM/DSS in colon tissue. It also
      induced apoptosis and regulated the AKT/FOXO3a signaling pathway. Overall, this
      study indicates the potential value of pristimerin in suppressing colon
      tumorigenesis.

PMID- 29655683
TI  - Bronchodilator effects of Lignosus rhinocerotis extract on rat isolated airways
      is linked to the blockage of calcium entry.
AB  - BACKGROUND: Lignosus rhinocerotis (Cooke) Ryvarden is a popular medicinal
      mushroom used for centuries in Southeast Asia to treat asthma and chronic cough.
      The present study aimed to investigate the effect of this mushroom on airways
      patency. MATERIALS AND METHODS: The composition of L. rhinocerotis TM02 cultivar
      was analyzed. Organ bath experiment was employed to study the bronchodilator
      effect of Lignosus rhinocerotis cold water extract (CWE) on rat isolated airways.
      Trachea and bronchus were removed from male Sprague-Dawley rats, cut into rings
      of 2 mm, pre-contracted with carbachol before adding CWE into the bath in
      increasing concentrations. To investigate the influence of incubation time,
      tissues were exposed to intervals of 5, 15 and 30 min between CWE concentrations
      after pre-contraction with carbachol in subsequent protocol. Next, tissues were
      pre-incubated with CWE before the addition of different contractile agents,
      carbachol and 5-hydroxytrptamine (5-HT). The bronchodilator effect of CWE was
      compared with salmeterol and ipratropium. In order to uncover the mechanism of
      action of CWE, the role of beta-adrenoceptor, potassium and calcium channels was
      investigated. RESULTS: Composition analysis of TM02 cultivar revealed the
      presence of beta-glucans and derivatives of adenosine. The extract fully relaxed
      the trachea at 3.75 mg/ml (p < 0.0001) and bronchus at 2.5 mg/ml (p < 0.0001). It
      was observed that lower concentrations of CWE were able to fully relax both
      trachea and bronchus but at a longer incubation interval between concentrations.
      CWE pre-incubation significantly reduced the maximum responses of carbachol
      induced contractions (in both trachea, p = 0.0012 and bronchus, p = 0.001), and 5
      HT-induced contractions (in trachea, p = 0.0048 and bronchus, p = 0.0014).
      Ipratropium has demonstrated a significant relaxation effect in both trachea (p =
      0.0004) and bronchus (p = 0.0031), whereas salmeterol has only affected the
      bronchus (p = 0.0104). The involvement of beta2-adrenoceptor and potassium
      channel in CWE-mediated airway relaxation is ruled out, but the bronchodilator
      effect was unequivocally affected by influx of calcium. CONCLUSIONS: The
      bronchodilator effect of L. rhinocerotis on airways is mediated by calcium
      signalling pathway downstream of Galphaq-coupled protein receptors. The airway
      relaxation effect is both concentration- and incubation time-dependent. Our
      findings provide unequivocal evidence to support its traditional use to relieve
      asthma and cough.

PMID- 29655684
TI  - Protective role and mechanism of snakegourd peel against myocardial infarction in
      rats.
AB  - BACKGROUND: Injection of snakegourd peel (SP), an herb used in traditional
      Chinese medicine, is used to treat coronary artery disease and stable angina in
      China. However, its therapeutic role and mechanism of action for the treatment of
      myocardial infarction (MI) is not fully understood. PURPOSE: The present study
      was designed to investigate the effect of SP on MI-induced cardiac injury and
      elucidate its underlying molecular mechanisms. METHODS: To create an in vivo
      model of MI, we ligated the left coronary artery of Wistar rats. For our in vitro
      model of MI, we treated primary neonatal rat ventricular myocytes with hypoxia.
      Myocardial infarct size was measured by triphenyltetrazolium chloride (TTC)
      staining. Intracellular calcium concentration (Ca2+) was measured by confocal
      microscopy, and cardiomyocyte apoptosis was assessed by TUNEL assay. Western blot
      was applied to determine protein levels. RESULTS: Three days post-MI, SP
      significantly improved MI-induced impairment of cardiac function, as indicated by
      increased left ventricular systolic pressure (LVSP), maximum rate of left
      ventricular pressure rise and fall (+/- dp/dt max), and decreased left
      ventricular end-diastolic pressure (LVEDP). In addition, SP treatment markedly
      reduced the infarct size and serum lactate dehydrogenase (LDH) activity;
      inhibited cardiomyocyte apoptosis and Caspase-3 activation both in vivo and in
      vitro; and decreased intracellular calcium overload, Cav1.2, phosphorylated JNK
      (p-JNK), and p38 MAPK (p-p38 MAPK) levels in ischemic myocardium. CONCLUSION: SP
      alleviated cardiac ischemic injury and inhibited cardiomyocyte apoptosis by
      attenuating intracellular calcium overload, suppressing Caspase-3 activation, and
      downregulating protein expression of p-JNK and p-p38MAPK. These results suggest
      that SP may serve as a potential novel therapeutic drug for MI.

PMID- 29655685
TI  - Polygonum aviculare L. extract reduces fatigue by inhibiting neuroinflammation in
      restraint-stressed mice.
AB  - BACKGROUND: Chronic fatigue patients experience various neuropsychological
      symptoms, including fatigue behaviors, chronic pain, and depression. They also
      display immune system dysregulation. Polygonum aviculare L. extract (PAE) is a
      traditional herbal medicine used to treat inflammatory diseases by reportedly
      decreasing pro-inflammatory cytokine production. HYPOTHESIS/PURPOSE: We
      hypothesized that the anti-inflammatory properties of PAE would attenuate fatigue
      symptoms in a mouse model of restraint stress. STUDY DESIGN: We evaluated the
      effects of PAE on fatigue using three experimental groups: unstressed, vehicle
      treated stressed, and PAE-treated stressed mice. This restraint stress paradigm,
      comprised of restraint for 3 h daily for 15 days, was used to model chronic
      fatigue. METHODS: We compared lethargy-like behavior between our experimental
      groups using forced-swim, sucrose preference, and open-field tests once per week
      on days 7 and 14 of restraint stress. We also used histology and western blotting
      to evaluate pro-inflammatory cytokine expression in the brain and serum, and
      microglial activation in the brain. Finally, we used liquid chromatography/mass
      spectroscopy (LC/MS) to identify individual components of PAE, and applied cell
      culture techniques to test the effects of these components on neuronal cells in
      vitro. RESULTS: In restraint-stressed mice, PAE treatment decreased lethargy-like
      behavior relative to vehicle-treated animals. PAE treatment also reduced
      expression of fatigue-related factors such as corticosterone, serotonin, and
      catecholamines (adrenaline and noradrenaline) in the brain and serum, and
      decreased expression of CD68, Ibal-1, and the inflammatory cytokines TNF-alpha,
      IL-6, and IL-1beta in the brain. Together, these data indicate that PAE reduced
      fatigue and is anti-inflammatory. Furthermore, histopathological analyses
      indicated that PAE treatment recovered atrophic volumes and hepatic injuries.
      Finally, LC/MS analysis of PAE identified four individual chemicals: myricitrin,
      isoquercitrin, avicularin, and quercitrin. In neuronal cell cultures, treatment
      with these PAE components inhibited TNF-alpha production, confirming that PAE
      treatment reduces neuroinflammation. CONCLUSIONS: PAE treatment may reduce
      fatigue by suppressing neuroinflammation and the expression of fatigue-related
      hormones.

PMID- 29655686
TI  - Physakengose G induces apoptosis via EGFR/mTOR signaling and inhibits autophagic
      flux in human osteosarcoma cells.
AB  - BACKGROUND: Physakengose G (PG) is a new compound first isolated from Physalis
      alkekengi var. franchetii, an anticarcinogenic traditional Chinese medicine. PG
      has shown promising anti-tumor effects, but its underlying mechanisms remain
      unknown. PURPOSE: To investigate the anti-cancer effects of PG on human
      osteosarcoma cells and the underlying mechanisms. METHODS: Cell viability was
      measured by MTT assay. Apoptosis rates, mitochondrial membrane potential (MMP),
      reactive oxygen species (ROS) generation, and acidic vesicular organelles (AVOs)
      formation were determined by flow cytometry. Protein levels were analyzed by
      immunofluorescence and western blotting. RESULTS: PG inhibited cell proliferation
      and induced apoptosis in human osteosarcoma cells. PG treatment blocked EGFR
      phosphorylation and suppressed epidermal growth factor (EGF)-induced activation
      of downstream signaling molecules, such as AKT and mTOR. PG treatment resulted in
      lysosome dysfunction by altering lysosome acidification and LAMP1 levels, which
      led to autophagosome accumulation and autophagic flux inhibition. CONCLUSION: PG
      inhibits cell proliferation and EGFR/mTOR signaling in human osteosarcoma cells.
      Moreover, PG induces apoptosis through the mitochondrial pathway and impedes
      autophagic flux via lysosome dysfunction. Our findings indicate that PG has the
      potential to play a significant role in the treatment of osteosarcoma.

PMID- 29655687
TI  - The inhibitory potential of Broussochalcone A for the human cytochrome P450 2J2
      isoform and its anti-cancer effects via FOXO3 activation.
AB  - BACKGROUND: Broussonetia papyrifera (L.) Ventenat, a traditional medicinal herb,
      has been applied as a folk medicine to treat various diseases. Broussochalcone A
      (BCA), a chalcone compound isolated from the cortex of Broussonetia papyrifera
      (L.) Ventenat, exhibits several biological activities including potent anti
      oxidant, antiplatelet, and cytotoxic effects. PURPOSE: The purpose of this study
      is to elucidate the inhibitory effect of BCA against CYP2J2 enzyme which is
      predominantly expressed in human tumor tissues and carcinoma cell lines. STUDY
      DESIGN: The inhibitory effect of BCA on the activities of CYP2J2-mediated
      metabolism were investigated using human liver microsomes (HLMs), and its anti
      cancer effect against human hepatoma HepG2 cells was also evaluated. METHODS: Two
      representative CYP2J2-specific probe substrates, astemizole and ebastine, were
      incubated in HLMs with BCA. After incubation, the samples were analyzed using
      liquid chromatography-tandem mass spectrometry. To investigate the binding model
      between BCA and CYP2J2, we carried out structure-based docking simulations by
      using software and scripts written in-house. RESULTS: BCA inhibited CYP2J2
      mediated astemizole O-demethylation and ebastine hydroxylase activities in a
      concentration dependent manner with Ki values of 2.3 and 3.7 uM, respectively. It
      also showed cytotoxic effects against human hepatoma HepG2 cells in a dose
      dependent manner with activation of apoptosis related proteins. CONCLUSION:
      Overall, this was the first report of the inhibitory effects of BCA on CYP2J2 in
      HLMs. The present data suggest that BCA is a potential candidate for further
      evaluation for its CYP2J2 targeting anti-cancer activities.

PMID- 29655688
TI  - Novel RAS inhibitor 25-O-methylalisol F attenuates epithelial-to-mesenchymal
      transition and tubulo-interstitial fibrosis by selectively inhibiting TGF-beta
      mediated Smad3 phosphorylation.
AB  - BACKGROUND: Tubulo-interstitial fibrosis (TIF) is the common pathway in the
      chronic kidney disease (CKD). Epithelial-to-mesenchymal transition (EMT) is a
      major contributor to the TIF by the increased myofibroblasts. Renin-angiotensin
      system (RAS) is critical mediator on EMT in progressive CKD. Angiotensin II (ANG)
      mediates EMT and causes TIF by stimulating transforming growth factor-beta1 (TGF
      beta1). RAS activation could further activate TGF-beta1. Inhibition of the RAS is
      one of the most powerful therapies for progressive CKD. 25-O-methylalisol F (MAF)
      is a new tetracyclic triterpenoid compound isolated from the Alismatis rhizoma,
      which is extensively used for anti-hypertensive, diuretic and anti-hyperlipidemic
      effects. METHODS: Inhibitory effect of MAF on EMT is investigated in both TGF
      beta1- and ANG-induced tubular epithelial cells (NRK-52E) and fibroblasts (NRK
      49F). Western blot analysis, qRT-PCR, siRNA, immunofluorescence staining and co
      immunoprecipitation techniques were used to evaluate the inhibition of MAF on EMT
      and further revealed the intervention effects on RAS, TGF-beta/Smad and Wnt/beta
      catenin pathways. RESULTS: MAF treatment significantly inhibited TGF-beta1 and
      ANG-induced expressions of collagen I, fibronectin, alpha-SMA, vimentin and E
      cadherin at both mRNA and protein levels in the NRK-52E and NRK-49F cells. The
      action mechanism revealed that MAF significantly ameliorated upregulation of
      angiotensinogen, renin, ACE and AT1R expressions. Further, MAF attenuated
      upregulation of Smad3 phosphorylation and downregulation of Smad7, but did not
      affect the phosphorylation of Smad2, PI3K, ERK1/2 and p38 expressions and Smad4
      expression in NRK-52E cells. Co-immunoprecipitation analysis indicated that MAF
      selectively blocked the combination of Smad3 with TGFbetaRI and Smad3 with SARA
      without interfering with the Smad2, TGFbetaRI and SARA interaction. Additionally,
      MAF suppressed the expressions of Wnt1 and beta-catenin as well as its downstream
      target Snail1, Twist, MMP-7, PAI-1 and FSP1 expressions in NRK-52E cells.
      CONCLUSIONS: MAF simultaneously targeted multiple RAS components and it was a
      novel RAS inhibitor. MAF inhibited EMT by Smad3-specific signaling in the TGF
      beta/Smad-dependent pathway and Wnt/beta-catenin pathway. MAF has an important
      effect on crosstalk between the TGF-beta/Smad and Wnt/beta-catenin pathway in EMT
      process by activation of RAS.

PMID- 29655689
TI  - European regulation model for herbal medicine: The assessment of the EU monograph
      and the safety and efficacy evaluation in marketing authorization or registration
      in Member States.
AB  - BACKGROUND: The European Union (EU) has created a regulatory framework for herbal
      medicinal products (HMPs) since the enforcement of Directive 2004/24/EC.
      Substantial achievements have been made, with 1719 traditional use marketing
      registrations (TURs) and 859 well-established use marketing authorizations (WEU
      MAs) for HMPs granted by the end of 2016. Apparently, the European regulation
      model has worked out well and in that the essential feature is the use of EU
      herbal monographs into those granted WEU-MAs and TURs. PURPOSE: A systematic
      analysis of the European regulation model for HMPs and the EU herbal monograph's
      part of this model are undertaken to assist understanding of the EU legislation
      particularly for interested parties those from outside EU area, and afterwards,
      to help in decision-making in the HMPs registration in European market for
      pharmaceutical companies, as well as in the establishment of legislation in
      countries with strong traditional use of herbal remedies. METHODS: A search of
      PubMed, ScienceDirect, the European Medicines Agency website and the Heads of
      Medicines Agencies website was conducted (up to December 2017), and the available
      information on regulation of HMPs in the EU was collected. RESULTS: The
      evaluation of applications by National Competent Authorities (NCAs) at a national
      level together with the assessment of EU monographs by the Committee on Herbal
      Medicinal Products (HMPC) at the European level constitute the European
      regulation framework for HMPs. As the scientific opinion about the safety and
      efficacy of HMPs from HMPC, the EU herbal monographs have been given a
      constitutional-based meaning to the TURs and WEU-MAs of HMPs and play a
      supportive function in the marketing procedure in Member States. CONCLUSION: The
      European framework has provided a powerful regulation model for harmonization of
      scientific assessment and facilitation of product marketing. For the
      pharmaceutical industries particularly those outside the EU, optimal use of the
      EU herbal monograph in their marketing procedure in Europe could be of great
      benefit. Furthermore, this model is well worth learning from for other countries
      and regions outside the EU to help the establishment of legislation in countries
      with strong traditional use of herbal remedies and contribute to the safe use of
      traditional herbal medicine.

PMID- 29655690
TI  - BG-4, a novel bioactive peptide from momordica charantia, inhibits
      lipopolysaccharide-induced inflammation in THP-1 human macrophages.
AB  - BACKGROUND: Bitter melon (Momordica charantia) is a commonly used food crop for
      management of a variety of diseases most notably for control of diabetes, a
      disease associated with aberrant inflammation. PURPOSE: To evaluate the anti
      inflammatory property of BG-4, a novel bioactive peptide isolated from the seed
      of bitter melon. METHODS: Differentiated THP-1 human macrophages were pre-treated
      with BG-4 and stimulated with lipopolysaccharide. Pro-inflammatory cytokines IL-6
      and TNF-alpha were measured by enzyme-linked immunosorbent assay. The mechanism
      of action involving activation of NF-kappaB and phosphorylation of ERK and STAT3
      was measured by western blot and immunofluorescence. The production of
      intracellular reactive oxygen species was evaluated by fluorescence microscopy
      and fluorescence spectrophotometry. RESULTS: BG-4 dose dependently reduce the
      production of pro-inflammatory cytokines IL-6 and TNF-alpha. The ability of BG-4
      to reduce production of cytokines are associated with reduced phosphorylation of
      ERK and STAT3 accompanied by reduced nuclear translocation of p65 NF-kappaB
      subunit. The mechanism of action is reduction of LPS-induced production of
      intracellular reactive oxygen species. CONCLUSION: Our results demonstrated the
      ability of BG-4, a novel peptide from the seed of bitter melon, to exert anti
      inflammatory action. This could explain the traditional use of bitter melon
      against diseases associated with aberrant and uncontrolled inflammation.

PMID- 29655691
TI  - Functionalized liposomes and phytosomes loading Annona muricata L. aqueous
      extract: Potential nanoshuttles for brain-delivery of phenolic compounds.
AB  - BACKGROUND: Multi-target drugs have gained significant recognition for the
      treatment of multifactorial diseases such as depression. Under a screening study
      of multi-potent medicinal plants with claimed antidepressant-like activity, the
      phenolic-rich Annona muricata aqueous extract (AE) emerged as a moderate
      monoamine oxidase A (hMAO-A) inhibitor and a strong hydrogen peroxide (H2O2)
      scavenger. PURPOSE: In order to protect this extract from gastrointestinal
      biotransformation and to improve its permeability across the blood-brain barrier
      (BBB), four phospholipid nanoformulations of liposomes and phytosomes
      functionalized with a peptide ligand promoting BBB crossing were produced.
      METHODS: AE and nanoformulations were characterized by HPLC-DAD-ESI-MSn, HPLC
      DAD, spectrophotometric, fluorescence and dynamic light scattering methods.
      Cytotoxicity and permeability studies were carried out using an in vitro
      transwell model of the BBB, composed of immortalized human microvascular
      endothelial cells (hCMEC/D3), and in vitro hMAO-A inhibition and H2O2 scavenging
      activities were performed with all samples. RESULTS: The encapsulation/binding of
      AE was more efficient with phytosomes, while liposomes were more stable,
      displaying a slower extract release over time. In general, phytosomes were less
      toxic than liposomes in hCMEC/D3 cells and, when present, cholesterol improved
      the permeability across the cell monolayer of all tested nanoformulations. All
      nanoformulations conserved the antioxidant potential of AE, while
      phosphatidylcholine interfered with MAO-A inhibition assay. CONCLUSIONS: Overall,
      phytosome formulations registered the best performance in terms of binding
      efficiency, enzyme inhibition and scavenging activity, thus representing a
      promising multipotent phenolic-rich nanoshuttle for future in vivo depression
      treatment.

PMID- 29655692
TI  - Effects of Xin-Ji-Er-Kang on heart failure induced by myocardial infarction: Role
      of inflammation, oxidative stress and endothelial dysfunction.
AB  - BACKGROUND: Xin-Ji-Er-Kang (XJEK) is a Chinese herbal formula, which has been
      reported to exert effective protection on cardiovascular diseases like
      hypertension and myocarditis. PURPOSE: To elucidate the protective effects of
      XJEK on heart failure (HF) induced by myocardial infarction (MI) through the
      amelioration of inflammation, oxidative stress (OS) and endothelial
      dysfunction(ED). MATERIALS AND METHODS: Fifty-seven male KM mice were randomized
      into the following six groups (n = 9-10 for each): control group, model group,
      MI+XJEK low dose group(XJEKL) group, MI+XJEK middle dose group(XJEKM), MI+XJEK
      high dose group(XJEKH), and MI+fosinopril group (positive control group). After
      treatment for four weeks, electrocardiography (ECG) and haemodynamics were
      recorded. Serum and tissues were collected for further analysis. Endothelium
      dependent relaxation induced by acetylcholine was assessed in isolated thoracic
      aorta ring experiment. Hematoxylin and eosin (HE) and Van Gieson (VG) staining
      were used to detect the pathological changes of heart and thoracic aorta.
      Colorimetric analysis was employed to determine serum nitric oxide level (NO),
      malondialdehyde (MDA) concentration and superoxide dismutase (SOD) activity.
      ELISA was used to detect serum B-type natriuretic peptide (BNP) and serum
      inflammatory cytokines, as well as endothelial NO synthetase (eNOS),
      angiotensinII (Ang II) and endothelin-1(ET-1) concentration in both serum and
      cardiac tissues. Immunohistochemistry and Western blotting (WB) were employed to
      detect eNOS and inflammatory cytokine expressions in cardiac tissues. RESULTS:
      XJEK administration markedly ameliorated cardiac dysfunction and abnormal ECG
      manifested by decreased weight/body weight (HW/BW) ratio, BNP and remedied
      hypertrophy of cardiomyocytes and deposition of collagen, which might be in part
      attributed to the increased SOD and decreased MDA in serum. Furthermore, XJEK
      administration improved ED with boosted eNOS activities in serum and cardiac
      tissues, as well as up-regulated NO levels in serum, down-regulated Ang II and ET
      1 content in serum and cardiac tissues. Lastly, protein expression of pro
      inflammation cytokines significantly decreased, and anti-inflammatory cytokine
      was significantly enhanced in serum and cardiac tissues compared to model group.
      CONCLUSION: XJEK may exert beneficial effects on HF induced by MI in mice, and
      the underlying mechanism may be attributable to the amelioration of ED, anti-OS
      and anti-inflammation effects.

PMID- 29655693
TI  - Molecular modeling and in vitro approaches towards cholinesterase inhibitory
      effect of some natural xanthohumol, naringenin, and acyl phloroglucinol
      derivatives.
AB  - BACKGROUND: Many natural products, particularly phenolic compounds, have been
      reported to have a strong inhibition against acetylcholinesterase (AChE) and
      butyrylcholinesterase (BChE), the key enzymes in the pathology of Alzheimer's
      disease (AD). HYPOTHESIS: Therefore, we hypothesized that some xanthahumol,
      naringenin, and acyl phloroglucinol derivatives (1-14) isolated from Humulus
      lupulus L. (hops) may have an inhibitory potential against AChE and BChE.
      METHODS: Inhibitory potential of compounds 1-14 were tested against AChE and BChE
      using ELISA microtiter assay. Different molecular docking simulations, including
      IFD and GOLD protocols, were implemented to verify the interactions between the
      ligands and the active site amino acids and also their binding energies inside
      the catalytic crevices of AChE and BChE. ADME/Tox analysis were used to determine
      pharmacological activities of the compounds. RESULTS: Among them, 3-hydroxy
      xanthohumol (IC50 = 51.25 +/- 0.88 uM) and xanthohumol (IC50 = 71.34 +/- 2.09
      uM), displayed a moderate AChE inhibition in comparison to that of the reference
      (galanthamine, IC50 = 2.52 +/- 0.15 uM). In addition to 3-hydroxy-xanthohumol
      (IC50 = 63.07 +/- 3.76 uM) and xanthohumol (IC50 = 32.67 +/- 2.82 uM), 8
      prenylnaringenin (IC50 = 86.58 +/- 3.74 uM) also showed micromolar-range
      inhibition against BChE (galanthamine, IC50 = 46.58 +/- 0.91 uM). Rest of the
      compounds were found to be either inactive or having inhibition below 50%.
      Prediction of pharmacokinetic studies suggested that all the ligands revealed
      acceptable drug-like profiles. Docking simulations demonstrate not only the
      prediction of ligand binding energies of the compounds inside the catalytic
      domains of the targets, but also highlight the critical amino acids contributing
      to stabilizations of the ligands. CONCLUSION: Our findings revealed that
      xanthohumol in particular could be considered as lead molecule to explore new
      cholinesterase inhibitors for AD.

PMID- 29655694
TI  - Tatanan A from the Acorus calamus L. root inhibited dengue virus proliferation
      and infections.
AB  - BACKGROUND: Acorus calamus l. (Acoraceae) is a well-known traditional Chinese
      medicinal plant, whose root are historically mainly used to treat
      neurodegenerative diseases, and for cholera treatment. This datum strongly
      indicates the antimicrobial activity of A. calamus. PURPOSE: Our goal is to find
      the active constituents of A. calamus to treat dengue virus (DENV) infections,
      and to study the effects and mechanisms of these active substances. METHODS: The
      root of A. calamus was extracted by ethanol. Mosquito larva C6/36 cells were used
      for DENV2 replication and transfection host. Mouse kidney fibroblast cells (BHK
      21) were used as a host cell to study the infection ability of the virus. DENV2
      induced cytopathic effect (CPE) and plaque assay were used to evaluate the
      inhibitory effect of A. calamus extracts on DENV2 infectivity inhibition. The
      levels of E and NS1 protein expression were measured by real-time PCR and western
      blot assays. RESULTS: 12 compounds were isolated from ethanol extract of A.
      calamus root, tatanan A showed the best anti-DENV ability among these 12
      compounds, which significantly alleviated DENV2-induced CPE and cytotoxicity
      effects, with an EC50 of 3.9 uM. In addition, RNA replication assay further
      confirmed the antivirus ability of tatanan A. Time-addition assay showed that
      tatanan A affected the early stage of viral RNA replication, which in turn
      inhibited mRNA and protein levels of DENV2. CONCLUSIONS: These results
      demonstrated the anti-DENV2 effect of tatanan A, in inhibiting DENV2 RNA
      replication and infections. In summary, tatanan A was found to be a novel natural
      DENV inhibitor and a potential candidate for the treatment of DENV infectious
      disease.

PMID- 29655695
TI  - Alisma orientale extract exerts the reversing cholestasis effect by activation of
      farnesoid X receptor.
AB  - BACKGROUND: Cholestasis is a clinical syndrome of liver damage that is caused by
      accumulation of bile acids in the liver and systemic circulation. Farnesoid X
      receptor (FXR) can regulate synthesis, metabolism, and excretion of bile acids.
      The rhizomes of Alisma orientale is a well-known traditional Chinese medicine to
      treat edema, obesity, gonorrhea, leukorrhea, diarrhea, hyperlipidemia, and
      diabetes in China. HYPOTHESIS/PURPOSE: We hypothesized Alisma orientale extract
      (AOE) to exert hepatoprotective effect against alpha-naphthylisothiocyanate
      (ANIT) induced cholestasis in rat. We aimed to investigate the mechanism of AOE.
      STUDY DESIGN: Male Sprague Dawley rats with intrahepatic cholestasis induced by
      ANIT were treated with AOE (150, 300, or 600 mg/kg). Rats receiving vehicle (0.5%
      CMC-Na) served as control. METHODS: 48 h after ANIT administration, rats were
      sacrificed. Blood was collected to obtain serum and livers were removed for
      histopathology and protein preparation. Biochemical indicators in serum were
      determined using commercial kits and triterpenoids were determined by liquid
      chromatography tandem Qtrap mass spectrometry. Proteomics was analyzed by liquid
      chromatography tandem ion-trap mass spectrometry. The differently expressed
      proteins were analyzed via the network database and verified by western blotting.
      The interaction between triterpenoids and FXR were evaluated by luciferase assay
      and molecular docking. RESULTS: AOE treatment significantly decreased the serum
      AST, ALT, TBIL, and intrahepatic TBA and improved the liver pathologic change
      induced by ANIT. Proteomics analysis indicated that AOE regulated proteins
      related to bile acid homeostasis via activating farnesoid X receptor (FXR)
      signaling pathway. Luciferase assay and molecular docking results indicated that
      triterpenoids could activate FXR, which resulting in ameliorative accumulation of
      bile acids in the liver by increase of metabolism and transportation for bile
      acids, and decrease of synthesis for bile acids. CONCLUSION: AOE protected
      against rat liver injury and cholestasis induced by ANIT by activation of
      farnesoid X receptor, suggesting that A. orientale could be regarded as a
      potential hepatoprotective drug.

PMID- 29655696
TI  - Syringin prevents bone loss in ovariectomized mice via TRAF6 mediated inhibition
      of NF-kappaB and stimulation of PI3K/AKT.
AB  - BACKGROUND: Syringin, also called eleutheroside B, is a main bioactive phenolic
      glycoside in Acanthopanax senticosus (Rupr. et Maxim.) Harms. Based on the
      "kidney dominates bone" theory of TCM, A. senticosus can strengthen bone and
      Syringin may be one of the responsibilities. PURPOSE: The objectives of this
      study were to estimate the osteoporotic activity of Syringin and reveal the
      possible molecular mechanisms in vivo. METHODS: Sixty female ICR mice were
      randomly assigned into sham operated group (SHAM, treated with vehicle) and five
      ovariectomized subgroups (n = 10 each), treated with vehicle as OVX group,
      estradiol valerate (EV, 1 mg/kg/day) as positive group, and Syringin (10, 20 and
      40 mg/kg/day) as low, moderate and high dosage groups. The therapeutic effect of
      Syringin against osteoporosis was systematically analyzed by determining the bone
      mineral density (BMD), bone biomechanical properties, bone microarchitecture and
      serum biochemical parameters, and the molecular mechanism was also evaluated.
      RESULTS: After three months of orally administrated intervention, Syringin (10,
      20 and 40 mg/kg/day) significantly improved the BMD, bone maximum load and
      trabecular bone microarchitecture in ovariectomized mice, evidenced by the
      increased bone mineral content, tissue mineral content, tissue mineral density,
      trabecular thickness and trabecular number, as well as the decreased trabecular
      separation in OVX mice. Meanwhile, the activities of tartrate-resistant acid
      phosphatase, deoxypyridinoline and cathepsin K in OVX mice were also inhibited by
      Syringin, while the increased body weight and decreased uterus weight seemed not
      influenced by Syringin administration. Concerning the underlying molecular
      mechanisms, Syringin significantly downregulated the expression of tumor-necrosis
      factor receptor-associated factor 6 (TRAF6), nuclear factor kappa B (NF-kappaB)
      and receptor activator of nuclear factor kappa B ligand (RANKL) proteins levels,
      upregulated the expression of osteoprotegerin (OPG), phosphoinositide 3-kinase
      (PI3K) and protein kinase B (AKT) levels, suggesting that Syringin prevented bone
      lost by TRAF6-mediated inhibition of NF-kappaB and stimulation of PI3K/AKT, and
      subsequently increasing the OPG/RANKL ratio and inhibiting the
      osteoclastogenesis, finally promoting bone formation. CONCLUSIONS: All of the
      data implied Syringin possessed the potent anti-osteoporosis activity on
      ovariectomized mice, and the underlying molecular mechanism may be related to the
      NF-kappaB and PI3K/AKT signaling pathways.

PMID- 29655697
TI  - Leaves of Acer palmatum thumb. Rescues N-ethyl-N-nitrosourea (ENU)-Induced
      retinal degeneration in mice.
AB  - BACKGROUND: In the East Asia, the genus Acer (Aceraceae) is a herbal medicine
      that is used to treat various diseases, including hemostasis, hepatic disorders,
      traumatic bleeding and poor eyesight. However, the effects of Acer palmatum
      thumb. on retinal degeneration are unknown. AIM: In this study, we investigated
      whether Acer palmatum thumb.ethanol extract (KIOM-2015E) can protect eyes from
      retinal degeneration. Our research investigated whether KIOM-2015E could have a
      protective effect in the retinal degenerating mouse model induced by N-ethyl-N
      nitrosourea (ENU). MATERIALS AND METHODS: Retinal degeneration was induced by a
      single intraperitoneal injection of ENU in ICR mice. KIOM-2015E (100, 200 mg/kg)
      was orally administered once per day. The eyeballs were embedded and lysed after
      drug administration to examine the histological changed and protein expression
      levels. RESULTS: The ENU-induced retinal degeneration model exhibited increased
      photoreceptor cell death and a loss of the outer nuclear layer. Additionally, the
      expression of PKCalpha and OPN1SW was reduced, and that of GFAP and Nestin was
      increased in ENU-treated retinal tissues. CONCLUSION: KIOM-2015E treatment
      ameliorated the ENU-induced retinal degeneration. KIOM-2015E prevents ENU-induced
      retinal degeneration by modulating protein expression and the thickness of the
      outer nuclear layer in the retina.

PMID- 29655698
TI  - Down-regulation of lncRNA, GAS5 decreases chemotherapeutic effect of dendrosomal
      curcumin (DNC) in breast cancer cells.
AB  - BACKGROUND: Despite positive results obtained from anticancer activities of
      curcumin, there are some obstacles that limit its use as an anticancer agent.
      HYPOTHESIS/PURPOSE: Different methods such as employing the dendrosomal curcumin
      (DNC) were examined to overcome such problems. There is increasing evidence
      representing long non-coding RNAs play important roles in biological processes.
      In this study, we focused on the roles of GAS5 in the anti-cancer effects of DNC
      on breast cancer. METHODS: We used several methods including MTT assay, apoptosis
      assay, cell cycle analysis, transwell migration assay and RT-PCR. RESULTS: We
      observed a significant increase in the expression of Tusc7, and GAS5 genes with
      DNC treatment of MCF7, MDA-MB231, and SKBR3 cells. Also, the combination of GAS5
      down-regulation and DNC treatment showed lower percentages of apoptotic cells and
      a higher level of penetration through the membrane compared with DNC treatment
      alone. Furthermore, DNC induced a significant increase in the number of cells in
      sub G1/G1 phase and a decrease in the G2/M phase of the cell cycle. But, after
      GAS5 down-regulation alone opposite results was observed compared to DNC.
      CONCLUSION: We observed that GAS5 down-regulation can suppress many aspects of
      DNC anti-cancer effects in breast cancer cells, it seems that co-treatment with
      DNC and GAS5 over-expression may provide a clinically useful tool for drug
      resistance breast cancer cells.

PMID- 29655699
TI  - Scutellarin protects against vascular endothelial dysfunction and prevents
      atherosclerosis via antioxidation.
AB  - BACKGROUND: Scutellarin is the major constituent responsible for the clinical
      benefits of Erigeron breviscapus (Vant.) Hand.-Mazz which finds a long history of
      ethnopharmacological use in Traditional Chinese Medicine. Scutellarin as a pure
      compound is now under investigation for its protections against various tissue
      injuries. PURPOSE: This study aims to examine the effects of scutellarin on
      oxidative stress-induced vascular endothelial dysfunction and endothelial cell
      damage, and then to evaluate the therapeutic efficacy of scutellarin in
      preventing atherosclerosis in rats. METHODS: Radical scavenging ability of
      scutellarin was determined in vitro. Impact of scutellarin on endothelium
      dependent relaxation (EDR) of rabbit thoracic aortic rings upon 1, 1-diphenyl-2
      picrylhydrazyl (DPPH) challenge was measured. Influences of scutellarin pre
      treatment on the levels of reactive oxygen species (ROS), activities of
      antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase and
      catalase, and the expression of SOD1 and NADPH oxidase 4 (Nox4) in human
      umbilical vein endothelial cells (HUVECs) injured by H2O2 were examined. Anti
      atherosclerotic effect of scutellarin was evaluated in rats fed with high fat
      diet (HFD). RESULTS: Scutellarin showed potent antioxidant activity in vitro.
      Pretreatment of scutellarin retained the EDR of rabbit thoracic aortic rings
      damaged by DPPH. In H2O2 injured-HUVECs the deleterious alterations in ROS levels
      and antioxidant enzymes activity were reversed by scutellarin and the mRNA and
      protein expression of SOD1 and Nox4 were restored also. Oral administration of
      scutellarin dose-dependently ameliorated hyperlipidemia in HFD-fed rats and
      alleviated oxidative stress in rat serum, mimicking the effects of reference drug
      atorvastatin. CONCLUSION: Scutellarin protects against oxidative stress-induced
      vascular endothelial dysfunction and endothelial cell damage in vitro and
      prevents atherosclerosis in vivo through antioxidation. The results rationalize
      further investigation into the clinical use of scutellarin in cardiovascular
      diseases.

PMID- 29655700
TI  - Effects on oral fat load of a nutraceutical combination of fermented red rice,
      sterol esters and stanols, curcumin, and olive polyphenols: A randomized, placebo
      controlled trial.
AB  - BACKGROUND: In literature, there are several studies about the effects of
      nutraceutical combinations at fasting, but data in post-prandial phase are
      lacking. PURPOSE: We planned a study to evaluate the efficacy and safety of a
      nutraceutical agent containing fermented red rice, phytosterols and olive
      polyphenols compared to placebo in a sample of Caucasian patients with low
      cardiovascular risk, both at fasting and after an oral fat load. STUDY DESIGN:
      Eighty patients were randomized to receive, as addition to diet and physical
      activity, a nutraceutical combination containing fermented red rice, sterol
      esters and stanols, curcumin, and olive polyphenols or placebo (control group),
      once a day. METHODS: We evaluated at baseline, and after 3 months: body mass
      index, fasting plasma glucose, lipid profile, soluble intercellular adhesion
      molecule-1, soluble vascular cell adhesion molecule-1, and soluble endothelial
      leukocyte adhesion molecule-1. We evaluated these parameters both at fasting, and
      after an oral fat load. RESULTS: Nutraceutical combination gave a reduction of
      total cholesterol, triglycerides, and low-density lipoprotein cholesterol, both
      compared to baseline (p < 0.05 for all), and to placebo (p < 0.05 for all). We
      recorded a reduction of soluble intercellular adhesion molecule-1, soluble
      vascular cell adhesion molecule-1, and sE-selectin in the group treated with
      nutraceutical combination, both compared to baseline (p < 0.05 for all), and to
      placebo (p < 0.05 for all). Parameters recorded during oral fat load improved
      compared to the oral fat load performed at baseline with the nutraceutical
      combination. CONCLUSIONS: The nutraceutical combination of fermented red rice,
      sterol esters and stanols, curcumin, and olive polyphenols seems to be effective
      in improving lipid profile and markers of endothelial damage in dyslipidemic
      patients in primary prevention at low risk for developing cardiovascular disease.
      The true novelty of this study, however, is the improvement of endothelial damage
      after an oral fat load compared to placebo.

PMID- 29655701
TI  - Apoptosis and pro-death autophagy induced by a spirostanol saponin isolated from
      Rohdea chinensis (Baker) N. Tanaka (synonym Tupistra chinensis Baker) on HL-60
      cells.
AB  - BACKGROUND: Our previous study has revealed that the spirostanol saponins
      isolated from the rhizomes of Rohdea chinensis (Baker) N. Tanaka (synonym
      Tupistra chinensis Baker) (Convallariaceae) (a reputed folk medicine) exhibited
      potent antiproliferative activity. However, the underlying mechanism of purified
      saponins remains unclear. More studies are necessary to assess the apoptosis and
      autophagy activities of the saponins from R. chinensis and clarify their
      antiproliferative mechanisms. PURPOSE: The present study certificated the
      potential antiproliferative activity and mechanism of 5beta-spirost-25(27)-en
      1beta,3beta-diol-1-O-alpha-L-rhamnopyranosyl-(1->2)- beta-D-xylopyranosyl-3-O
      alpha-L-rhamnopyranoside (SPD), a spirostanol saponin from R. chinensis, against
      human acute promyelocytic leukemia cells (HL-60). METHODS: The antiproliferative
      activity of SPD in vitro was evaluated by MTT assay compared with cis
      dichlorodiammineplatinum (II). The autophagic activity was assessed using MDC
      staining and western blot, cell apoptosis inspection was detected by Annexin V
      FITC/PI double staining and the mitochondrial membrane potential was detected by
      JC-1 fluorescence dye combined with flow cytometry. The potential mechanisms for
      protein levels of apoptosis and autophagy were evaluated by western blot.
      RESULTS: Treatment of HL-60 cells with SPD resulted in growth inhibition (IC50
      value of 2.0 +/- 0.2 uM, after 48 h treatment) and induction of apoptosis and
      autophagy. Results from Annexin V-FITC/PI double-staining assay and mitochondrial
      membrane potential detection showed that apoptosis was happened after SPD
      treatment. The regulation of caspase-3, Bax, Bcl-2, PARP following SPD treatment
      contributed to the induction of mitochondria-dependent apoptosis. Meanwhile, SPD
      induced autophagy related with Akt/mTOR/p70S6K signaling and activated of AMPK
      signaling pathway. Furthermore, blocking autophagy with bafilomycin A1 reduced
      the cytotoxicity of SPD in HL-60 cells. CONCLUSION: The antiproliferative,
      apoptosis and pro-death autophagy activities of SPD suggested that spirostanol
      saponins from R. chinensis would be a potential cytotoxic candidate against acute
      promyelocytic leukemia.

PMID- 29655702
TI  - 4-(2-(4-chlorophenyl)-1-((4-chlorophenyl)amino)ethyl)benzene-1, 3-diol is a
      potential agent for gout therapy as a dual inhibitor of XOD and NLRP3.
AB  - BACKGOUND: Gout is an inflammatory arthritis characterized by abrupt self
      limiting attacks of inflammation caused by precipitation of monosodium urate
      crystals (MSU) in the joint. Both anti-hyperuricemia and anti-inflammation could
      be gout therapeutic strategies, whereas ideal drugs for gout treatment are
      deficient. PURPOSE: 4-(2-(4-chlorophenyl)-1-((4-chlorophenyl)amino)ethyl)benzene
      1, 3-diol (CBED) was obtained from a cluster of deoxybenzoins derivatives
      synthesized by our research group with potent anti-hyperuricemic and anti
      inflammatory activities, which was expected to be a dual inhibitor of xanthine
      oxidase (XOD) and NOD-like receptor protein 3 (NLRP3). This study aimed to
      investigate effects of CBED on XOD and NLRP3 in vitro, as well as the possible
      mechanisms by which CBED improved gout in vivo. METHODS: After molecular docking
      detection, inhibitory effects of CBED on XOD and NLRP3 were evaluated in vitro.
      Subsequently, hyperuricemia and acute gouty arthritis animal models were
      established by potassium oxonate or MSU, respectively. After CBED treatment,
      serum uric acid levels, synovial interleukin (IL)-1beta concentrations, hepatic
      XOD activities, as well as synovial morphological changes were examined. More
      importantly, synovial expressions of NLRP3 inflammasome components including
      NLRP3, apoptosis-associated speck-like protein (ASC) and caspase-1 in rats were
      analyzed by immunofluorescence and western blot. RESULTS: In vitro, CBED
      obviously inhibited XOD activity with an IC50 value of 3.87 uM, moreover, it
      effectively inhibited MSU-induced NLRP3 inflammasome activation and IL-1beta over
      production in THP-1 cells. In addition, CBED dose-dependently decreased serum
      uric acid levels suppressed hepatic XOD activities in oxonate-induced
      hyperuricemic mice. On the other hand, CBED significantly improved MSU-induced
      ankle swelling and histopathological damage with elevated IL-1beta. In addition,
      NLRP3 inflammasome activation could be blocked by CBED treatment in rats with
      acute gouty arthritis. Notbly, CBED exhibited no effects on all these indicators
      in normal animals, predicting its safety. CONCLUSIONS: CBED might serve as a dual
      XOD and NLRP3 inhibitor for treatment of gout.

PMID- 29655703
TI  - The effects of wild bitter gourd fruit extracts on ICAM-1 expression in pulmonary
      epithelial cells of C57BL/6J mice and microRNA-221/222 knockout mice: Involvement
      of the miR-221/-222/PI3K/AKT/NF-kappaB pathway.
AB  - BACKGROUND: The extracts from wild bitter gourd fruit (WBGE) were reported to
      possess numerous pharmacological activities. However, the anti-inflammatory
      effects of WBGE on human lung epithelial cells and the underlying mechanisms have
      not been determined. PURPOSE: To evaluate the molecular basis of the effects of
      WBGE on intercellular adhesion molecule-1 (ICAM-1) expression in alveolar
      epithelial (A549) cells, C57BL/6 wild-type (WT) mice and microRNA (miR)-221/-222
      knockout (KO) mice with or without tumor necrosis factor (TNF-alpha; 3 ng/ml)
      treatment. STUDY DESIGN/METHODS: WT mice and miR-221/-222 KO mice were fed a
      control diet and divided into four groups (C: control mice; T: treated with TNF
      alpha alone; WBGE/T: pretreated with WBGE and then stimulated with TNF-alpha;
      WBGE: treated with WBGE alone). The effects of WBGE on ICAM-1 expression and the
      related signals in A549 cells and mice with or without TNF-alpha treatment were
      examined by Western blot and immunofluorescent staining. RESULTS: WBGE
      significantly decreased the TNF-alpha-induced ICAM-1 expression in A549 cells
      through the inhibition of phosphoinositide 3-kinase (PI3K)/ protein kinase B
      (AKT)/ nuclear factor- kappa B (NF-kappaB)/ inhibitor of NF-kappaB (IkappaB)
      phosphorylation and decreased leukocyte adhesion. In addition, WBGE reduced
      endogenous ICAM-1 expression and upregulated miR-221/-222 expression. The
      overexpression of miR-222 decreased PI3K/AKT/NF-kappaB/IkappaB and ICAM-1
      expression, which resulted in reducing monocyte adhesion. Moreover, WBGE reduced
      ICAM-1 expression in lung tissues of WT mice with or without TNF-alpha treatment
      and upregulated miR-221/222. WBGE did not affect the miR-221/-222 level and had
      little effect on ICAM-1 expression in miR-221/-222 KO mice. CONCLUSIONS: These
      results suggest that WBGE reduced ICAM-1 expression both under in vitro and in
      vivo conditions. The protective effects were mediated partly through the miR-221/
      222/PI3K/AKT/NF-kappaB pathway.

PMID- 29655705
TI  - Spatially Correlated Gene Expression in Bacterial Groups: The Role of Lineage
      History, Spatial Gradients, and Cell-Cell Interactions.
AB  - Gene expression levels in clonal bacterial groups have been found to be spatially
      correlated. These correlations can partly be explained by the shared lineage
      history of nearby cells, although they could also arise from local cell-cell
      interactions. Here, we present a quantitative framework that allows us to
      disentangle the contributions of lineage history, long-range spatial gradients,
      and local cell-cell interactions to spatial correlations in gene expression. We
      study pathways involved in toxin production, SOS stress response, and metabolism
      in Escherichia coli microcolonies and find for all pathways that shared lineage
      history is the main cause of spatial correlations in gene expression levels.
      However, long-range spatial gradients and local cell-cell interactions also
      contributed to spatial correlations in SOS response, amino acid biosynthesis, and
      overall metabolic activity. Together, our data show that the phenotype of a cell
      is influenced by its lineage history and population context, raising the question
      of whether bacteria can arrange their activities in space to perform functions
      they cannot achieve alone.

PMID- 29655706
TI  - Rare Presentation of Intraductal Papillary Neoplasm of the Bile Duct in a Patient
      With Ulcerative Colitis.

PMID- 29655704
TI  - A Library of Phosphoproteomic and Chromatin Signatures for Characterizing
      Cellular Responses to Drug Perturbations.
AB  - Although the value of proteomics has been demonstrated, cost and scale are
      typically prohibitive, and gene expression profiling remains dominant for
      characterizing cellular responses to perturbations. However, high-throughput
      sentinel assays provide an opportunity for proteomics to contribute at a
      meaningful scale. We present a systematic library resource (90 drugs * 6 cell
      lines) of proteomic signatures that measure changes in the reduced-representation
      phosphoproteome (P100) and changes in epigenetic marks on histones (GCP). A
      majority of these drugs elicited reproducible signatures, but notable cell line-
      and assay-specific differences were observed. Using the "connectivity" framework,
      we compared signatures across cell types and integrated data across assays,
      including a transcriptional assay (L1000). Consistent connectivity among cell
      types revealed cellular responses that transcended lineage, and consistent
      connectivity among assays revealed unexpected associations between drugs. We
      further leveraged the resource against public data to formulate hypotheses for
      treatment of multiple myeloma and acute lymphocytic leukemia. This resource is
      publicly available at https://clue.io/proteomics.

PMID- 29655707
TI  - Temporomandibular condylar morphology in diverse maxillary-mandibular skeletal
      patterns: A 3-dimensional cone-beam computed tomography study.
AB  - BACKGROUND: The authors evaluated the morphology and symmetry of the
      temporomandibular joint in participants with normodivergent and hyperdivergent
      skeletal class I, II, and III patterns. METHODS: A total of 80 participants were
      divided into 4 groups on the basis of their sagittal and vertical skeletal
      patterns. Cone-beam computed tomographic images were used to evaluate the condyle
      fossa relationship and the morphology and symmetry of the mandibular condyle. One
      way analysis of variance and Tukey post hoc tests were used to compare the mean
      values among the different groups. RESULTS: Participants with class II
      hyperdivergent patterns had the smallest anteroposterior (mean [standard
      deviation {SD}], 4.4 [1.6] millimeters) and mediolateral (10.5 [3.0] mm) condylar
      process widths among all 4 groups. The mean (SD) axial condylar angle was flatter
      in patients with class III hyperdivergent patterns (19.8 degrees  [5.1 degrees ])
      compared with the other groups. The mean (SD) anteroposterior differences of the
      condylar processes (2.9 [1.4] mm) in patients with class III hyperdivergent
      patterns were the greatest in all 4 groups. CONCLUSION: Participants in the group
      with class II hyperdivergent patterns have a smaller and narrower condyle
      compared with the other groups measured. Asymmetry was found among all groups,
      with participants with skeletal class III patterns having the most asymmetry. The
      most common condylar morphology in all groups examined was convex. PRACTICAL
      IMPLICATIONS: These results support the concept that morphology and symmetry of
      the temporomandibular joint varies in different skeletal patterns, presumably as
      an adaptive response to functional demands.

PMID- 29655708
TI  - Salivary flow rate after conventional and intensity-modulated radiation therapy.
AB  - BACKGROUND: Conventional 3-dimensional conformal radiation therapy (3DCRT) for
      head and neck cancer (HNC) can cause hyposalivation, leading to caries and tooth
      extraction-related osteoradionecrosis. Intensity-modulated radiation therapy
      (IMRT) delivers more focused radiation than does 3DCRT. To reduce hyposalivation,
      the Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC)
      guidelines limit salivary gland radiation dose. In this study, the authors
      compared the salivary flow rate in patients receiving 3DCRT and those receiving
      IMRT and evaluated the effect of their treatment satisfying the QUANTEC
      guidelines on hyposalivation. METHODS: The authors evaluated findings in 96
      patients with HNC who received radiation therapy (RT); 20 received unilateral
      3DCRT, 17 received bilateral 3DCRT, and 59 received IMRT. The authors measured
      stimulated whole saliva before radiation and 3 and 12 months after radiation. The
      authors defined hyposalivation as stimulated whole saliva less than 3.5 grams per
      5 minutes. RESULTS: At 12 months, 50% and 54% of patients receiving unilateral
      3DCRT and IMRT, respectively, exhibited nonstatistically significant
      hyposalivation compared with 71% of patients receiving bilateral 3DCRT (P = .2).
      A lower proportion of patients receiving IMRT (27%) and unilateral 3DCRT (5%) had
      decreased salivary flow (< 25% of baseline) than did those receiving bilateral
      3DCRT (59%; P < .004); fewer patients whose treatment satisfied the QUANTEC
      guidelines exhibited hyposalivation than patients whose treatment did not
      fullfill QUANTEC guidelines (39% versus 71%; P < .002). CONCLUSIONS: Twelve
      months after RT for HNC, treatment satisfying the QUANTEC guidelines resulted in
      decreased hyposalivation. Unilateral 3DCRT and IMRT may result in less
      hyposalivation than does bilateral 3DCRT. PRACTICAL IMPLICATIONS: Patients with
      HNC treated with modern RT techniques have a lower risk of developing
      hyposalivation, particularly if the QUANTEC guidelines are met, which also may
      result in decreased dental caries, tooth extractions, and postextraction
      osteoradionecrosis. Management of HNC requires a multidisciplinary team,
      including dentists and radiation oncologists.

PMID- 29655709
TI  - Phenolic contents and antioxidant capacities of wild and cultivated white lupin
      (Lupinus albus L.) seeds.
AB  - The aim of this study was to compare the antioxidant capacities and phenolic
      compound profiles of wild and cultivated Lupinus albus L. seeds. The total
      phenolic content (TPC), radical scavenging activity, ferric-reducing antioxidant
      power (FRAP) and antioxidant activity in an beta-carotene-linoleic acid emulsion
      were determined. Liquid chromatography-mass spectrometry was used to identify
      phenolics. The TPC of lupin seeds ranged from 4.36 to 7.24 mg gallic acid
      equivalent/g dry matter (d.m.). The dominant phenolics of all genotypes were two
      p-coumaric acid derivatives (0.74-1.61 and 0.66-1.63 mg/g d.m.) and apigenin-6,8
      di-C-glucoside (1.13-1.31 mg/g d.m.). The results of antioxidant assays of wild
      lupin extracts were similar to or lower than those of the cultivated variety.
      FRAP and ABTS+ scavenging activity were correlated with the contents of the more
      polar p-coumaric acid derivative and apigenin-6,8-di-C-glucoside. Generally,
      significant differences between cultivated and wild L. albus seeds were not found
      in antioxidant capacities and phenolic compound contents.

PMID- 29655710
TI  - Pectin-honey coating as novel dehydrating bioactive agent for cut fruit:
      Enhancement of the functional properties of coated dried fruits.
AB  - In this paper, a novel and sustainable process for the fruit dehydration was
      described. Specifically, edible coatings based on pectin and honey were prepared
      and used as dehydrating and antimicrobial agents of cut fruit samples, in this
      way promoting the fruit preservation from irreversible deteriorative processes.
      Pectin-honey coating was tested on apple, cantaloupe melon, mango and pineapple.
      The analysis were performed also on uncoated dehydrated fruits (control). The
      coated fruit evidenced enhanced dehydration percentage, enriched polyphenol and
      vitamin C contents, improved antioxidant activity and volatile molecules profile.
      Moreover, the antimicrobial activity against Pseudomonas and Escherichia coli was
      assessed. Finally, morphological analysis performed on fruit fractured surface,
      highlighted the formation of a non-sticky and homogeneous thin layer. These
      outcomes suggested that the novel fruit dehydration process, performed by using
      pectin-honey coating, was able to both preserve the safety and quality of
      dehydrated fruits, and enhance their authenticity and naturalness.

PMID- 29655711
TI  - Characterizations of the endogenous starch hydrolase inhibitors in acorns of
      Quercus fabri Hance.
AB  - The acorns of Quercus fabri Hance tree, or the mandarin duck fruits have been
      consumed by locals in the form of noodle, yet there is little scientific study.
      We found that they have much lower digestibility compared with that of rice
      flour. Solvent extraction using hexane, dichloromethane, and acetone-ethanol
      water (AEW) mixture yielded three fractions but the starch hydrolase inhibitors
      were only found in the AEW fraction. Using assay-guided fractionation of the
      extracts, we were able to further separate the active compounds by using Sephadex
      LH-20 column and characterize the inhibitor chemical identities by LC-MS(n). The
      main active compounds are ellagitannins including pedunculagin, punicalagin,
      castalagin, and eucalbanin. Our results indicate that the acorns from Quercus
      fabri Hance have potential for preparation of low glycemic index foods due to the
      endogenous starch hydrolase inhibitors.

PMID- 29655712
TI  - Enzyme assisted fermentation of potato pulp: An effective way to reduce water
      holding capacity and improve drying efficiency.
AB  - The effects of an enzyme-assisted fermentation technique on the water holding
      capacity (WHC) and drying characteristics of potato pulp were investigated.
      Potato pulp was fermented with Lactobacillus plantarum to increase the content of
      organic acids, reduce the pH of the pulp and assist in enhancing the enzymatic
      hydrolysis. Removal of pectin and cellulose reduced the WHC of potato pulp from
      16.84 to 6.83 and 9.64 g/g, respectively. Drying characteristics were determined
      using the air-drying process, which indicated that pectinase-assisted
      fermentation could remove pectin from potato pulp and shorten the air-drying time
      from 240 to 140 min, while cellulase had an opposite effect on the drying rate.
      This result was also confirmed by low field nuclear magnetic resonance (LF-NMR),
      which showed more mobile water and less bonded water in pectin-removed potato
      pulp samples.

PMID- 29655713
TI  - Enzymatic mitigation of 5-O-chlorogenic acid for an improved digestibility of
      coffee.
AB  - A p-coumaroyl esterase from Rhizoctonia solani was used to decrease 5-O
      chlorogenic acid (5-CQA) content in coffee powder. HPLC-UV showed a decline of up
      to 98% of 5-CQA after the enzyme treatment. Effects on aroma were determined by
      means of aroma extract dilution analysis. Flavour dilution factors of treated and
      control extract differed in four volatile compounds only. Effect on aroma and
      taste was evaluated by sensory tests. No significant differences were perceived,
      and no off-flavour nor off-taste was noted. As chlorogenic acids are suspected to
      cause stomach irritating effects in sensitive people, the enzyme treatment offers
      a technically feasible approach to improve the quality of coffee beverages by
      reducing 5-CQA concentration without significantly affecting the aroma and taste
      profile.

PMID- 29655714
TI  - The influence of food matrices on aptamer selection by SELEX (systematic
      evolution of ligands by exponential enrichment) targeting the norovirus P-Domain.
AB  - This study investigates the enrichment of aptamers targeting the norovirus
      protruding domain in the presence of foods often associated with norovirus
      outbreaks. The goal is to explore if and how the presence of food alters in vitro
      selection of aptamers and target binding of the enriched oligonucleotides. Our
      study demonstrates that the introduction of food to SELEX (systematic evolution
      of ligands by exponential enrichment) is either detrimental to enrichment of
      oligonucleotides with target-specific binding, or facilitates enrichment of non
      target-specific oligonucleotides. Moreover, a relationship between target binding
      of enriched oligonucleotides in presence of food and their selection condition
      was not observed. Our findings also suggest that a pathogen specific aptamer with
      application in food does not need to be selected in presence of the particular
      food, but may require properties beyond high affinity and selectivity to be
      applied for pathogen extraction and detection in undiluted food matrices.

PMID- 29655715
TI  - Extraction kinetic modelling of total polyphenols and total anthocyanins from
      saffron floral bio-residues: Comparison of extraction methods.
AB  - Analysis of the extraction kinetic modelling for natural compounds is essential
      for industrial application. The second order rate model was applied to estimate
      the extraction kinetics of conventional solid-liquid extraction (CSLE),
      ultrasound-assisted extraction (UAE) and microwave-assisted extraction (MAE) of
      total polyphenols (TPC) from saffron floral bio-residues at different solid-to
      liquid ratios (RS/L)(1:10, 1:20, 1:30, 1:50 g ml-1), ethanol 59% as solvent and
      66  degrees C temperature. The optimum solid-to-liquid ratios for TPC kinetics
      were 1:20 for CLSE, 1:30 for UAE and 1:50 for MAE. The kinetics of total
      anthocyanins (TA) and antioxidant activity (AA) were investigated for the optimum
      RS/L for each method. The results showed a good prediction of the model for
      extraction kinetics in all experiments (R2 > 0.99; NRMS 0.65-3.35%). The kinetic
      parameters were calculated and discussed. UAE, compared with the other methods,
      had the greater efficiency for TPC, TA and AA.

PMID- 29655716
TI  - Colonic fermentation of polyphenols from Chilean currants (Ribes spp.) and its
      effect on antioxidant capacity and metabolic syndrome-associated enzymes.
AB  - The Chilean wild currants Ribes magellanicum and R. punctatum are a good source
      of polyphenols. Polyphenolic-enriched extracts (PEEs) from both species were
      submitted to in vitro colonic fermentation to assess the changes in phenolic
      composition, antioxidant capacity and inhibition of metabolic syndrome-associated
      enzymes. The phenolic profiles of the fermented samples showed significant
      changes after 24 h incubation. Nine metabolites, derived from the microbial
      fermentation, were tentatively identified, including dihydrocaffeic acid,
      dihydrocaffeoyl-, dihydroferuloylquinic acid, 1-(3,4-dihydroxyphenyl)-3-(2,4,6
      trihydroxyphenyl)propan-2-ol (3,4-diHPP-2-ol), among others. The content of
      anthocyanins and hydroxycinnamic acids was most affected by simulated colonic
      conditions, with a loss of 71-92% and 90-100% after 24 h incubation,
      respectively. The highest antioxidant capacity values (ORAC) were reached after 8
      h incubation. The inhibitory activity against the enzyme alpha-glucosidase was
      maintained after the fermentation process. Our results show that simulated
      colonic fermentation exerts significant changes on the polyphenolic composition
      of these berries, modifying their health-promoting properties.

PMID- 29655717
TI  - Encapsulation of curcumin using supercritical antisolvent (SAS) technology to
      improve its stability and solubility in water.
AB  - This study aims to develop a formulation of a turmeric-based dye extract using
      supercritical antisolvent (SAS) technology and different encapsulating polymers
      to improve the aqueous stability and solubility of curcumin. The dye formulation
      obtained by SAS consists of a mixture of Eudragit(r) L100 and Pluronic(r) 127
      using tween 20 as a surfactant The characterization and quantification of
      curcumin extracts and the encapsulation product were conducted using high
      performance liquid chromatography (HPLC). The properties of the dye were
      determined using SEM, DSC, X-ray diffraction, particle size, zeta potential, and
      oxygen radical absorbance capacity (ORAC) to measure antioxidant capacity. The
      dye formulation contained a curcumin content of 4.45 ug/mL. The average diameter
      of the amorphous particles was 5667.4 nm, and the zeta potential was 11.21 mV.
      The largest aqueous stability and solubility was observed at pH 4. From color
      comparison with a solution of tartrazine 200 ug/mL solution of dye formulation
      based on curcuminoids is equivalent to an approximated 30 ug/mL tartrazine
      solution.

PMID- 29655718
TI  - Quantitative analyses of the bitterness and astringency of catechins from green
      tea.
AB  - Bitterness and astringency are two important quality attributes of green tea
      infusion, and catechins are the main contributor to the bitterness and
      astringency. The aim of this work was to quantitatively analyse the bitterness
      and astringency of green tea infusion according to the concentrations of
      catechins. The concentration-taste curves of catechins showed a pattern that fit
      the cubic functions, and their R2 values were higher than 0.956. The bitterness
      of green tea was highly correlated with the concentrations of (-)
      epigallocatechin gallate and (-)-epicatechin gallate (ECG) (R2 = 0.7769, p <
      0.01), and the astringency (R2 = 0.7878, p < 0.01) was highly correlated with the
      concentrations of ECG and flavonol glycosides (myricetin 3-O-galactoside and
      quercetin-3-O-rutinoside). Taste interactions between different catechins and
      between catechins and other substances were determined. These results may enhance
      the understanding of tea chemistry for improving the taste of products from green
      tea.

PMID- 29655719
TI  - Tea polyphenols enhance binding of porcine pancreatic alpha-amylase with starch
      granules but reduce catalytic activity.
AB  - The effects of tea polyphenols on binding of porcine pancreatic alpha-amylase
      (PPA) with normal maize starch granules were studied through solution depletion
      assays, fluorescence spectroscopy and initial rate kinetics. Only polyphenols
      which have inhibitory activity against PPA increased the binding of PPA with
      starch. The results are consistent with a binding equilibrium between
      polyphenols, starch and PPA. The dissociation constant (Kd) for PPA binding was
      decreased by tea polyphenols, with the effects greater for theaflavins than
      catechins and for galloylated than non-galloylated polyphenols. Tea polyphenols
      were also shown to increase the binding rate of PPA to starch. In addition, there
      were positive linear correlations between 1/Kd and reciprocal of competitive
      inhibition constant (1/Kic) and between 1/Kd and fluorescence quenching constant
      (KFQ). Despite the greater amount of PPA on the granules, starch hydrolysis is
      reduced because the polyphenol inhibition of PPA persists after binding to
      starch.

PMID- 29655720
TI  - Pretreatment with formic acid enhances the production of small peptides from
      highly cross-linked collagen of spent hens.
AB  - Small collagen peptides are associated with various benefits, such as bone and
      skin health. However, preparation of small collagen peptides from terrestrial
      vertebrate origins remains a challenge. Here, we show that pretreatment with
      formic acid enhanced the production of small collagen peptides from spent hen
      skin. After pretreatment with formic acid, the percentage of small peptides below
      2 kDa increased to 48.92% and 43.34% from 33.79% and 36.32% for heat-soluble
      collagen (HSC) and pepsin-soluble collagen (PSC), respectively. Pretreatment with
      formic acid degraded telopeptides and released the cross-links (pyrrole and
      pyridinoline), which made hen collagen more susceptible to papain hydrolysis. LC
      MS/MS results revealed that none of the peptides identified from HSC-FA (formic
      acid)-Papain and PSC-FA-Papain were derived from cross-linked telopeptides. These
      results demonstrated that formic acid assisted the hydrolysis of highly cross
      linked collagen of spent hens, and it might also be used to produce small
      collagen peptides from other aged, vertebrate collagens.

PMID- 29655721
TI  - Gamma irradiation-assisted degradation of rosmarinic acid and evaluation of
      structures and anti-adipogenic properties.
AB  - Radiation is a promising technique for improving the safety and shelf-life of
      processed foods. In the present investigation, the degradation mechanism and
      bioactivity improvement of rosmarinic acid (RA) were studied in response to
      various gamma irradiation doses (10, 20, and 50 kGy). RA exposed to gamma
      irradiation at 50 kGy was completely degraded and showed an increased inhibitory
      effect against 3 T3-L1 preadipocyte compare to the parent compound. Structures of
      the newly generated compounds 2-4 from irradiated RA at 50 kGy were elucidated
      based on spectroscopic methods, including 1H nuclear magnetic resonance (NMR) and
      mass spectrometry (MS). Interestingly, compounds 2 and 5 exhibited significantly
      enhanced anti-adipogenic properties in 3 T3-L1 cells compared to the original
      compound. These results provide evidence that structural changes in RA induced by
      gamma irradiation might enhance biological efficacy.

PMID- 29655722
TI  - A new strategy for statistical analysis-based fingerprint establishment:
      Application to quality assessment of Semen sojae praeparatum.
AB  - Semen sojae praeparatum with homology of medicine and food is a famous
      traditional Chinese medicine. A simple and effective quality fingerprint
      analysis, coupled with chemometrics methods, was developed for quality assessment
      of Semen sojae praeparatum. First, similarity analysis (SA) and hierarchical
      clusting analysis (HCA) were applied to select the qualitative markers, which
      obviously influence the quality of Semen sojae praeparatum. 21 chemicals were
      selected and characterized by high resolution ion trap/time-of-flight mass
      spectrometry (LC-IT-TOF-MS). Subsequently, principal components analysis (PCA)
      and orthogonal partial least squares discriminant analysis (OPLS-DA) were
      conducted to select the quantitative markers of Semen sojae praeparatum samples
      from different origins. Moreover, 11 compounds with statistical significance were
      determined quantitatively, which provided an accurate and informative data for
      quality evaluation. This study proposes a new strategy for "statistic analysis
      based fingerprint establishment", which would be a valuable reference for further
      study.

PMID- 29655723
TI  - Thermal behavior of inosine 5'-monophosphate in acidic form and as alkali and
      alkaline earth salts.
AB  - Inosine 5'-monophosphate in acidic form and its lithium, potassium, magnesium,
      calcium, strontium and barium were prepared from the sodium salt, characterized
      by elemental analysis and Fourier transform infrared spectroscopy and submitted
      to thermogravimetry (TG), differential thermal analysis (DTA), differential
      scanning calorimetry (DSC) and thermogravimetry coupled to infrared spectroscopy
      (TG-FTIR) of the volatile products evolved during heating. All the salts were
      hydrated containing from 4 to 7.5 H2O. After dehydration these salts decomposed
      releasing the nitrogenous base followed by the ribose group, and producing
      pyrophosphates as final residue. Evolved Gas Analysis (EGA) reveled the release
      of water, isocyanic acid and hydrocyanic acid during decomposition of the organic
      moiety. It was observed only water loss up to 200  degrees C. At temperatures
      above 200  degrees C, the nucleotides were unstable and decomposed, implying that
      foods containing those additives should be processed below this temperature.
      Finally, a general mechanism for the decomposition of the inosinates was
      proposed.

PMID- 29655724
TI  - Solid phase extraction with high polarity Carb/PSA as composite fillers prior to
      UPLC-MS/MS to determine six bisphenols and alkylphenols in trace level hotpot
      seasoning.
AB  - The present study reports an ultra high-performance liquid chromatography tandem
      mass spectrometry method for the simultaneous determination of six bisphenols
      (bisphenol A, bisphenol B and bisphenol F) and alkylphenols (4-nonylphenol, 4-n
      nonylphenol and octylphenol) in hotpot seasoning. Samples were dispersed in n
      hexane after addition of internal standards bisphenol A-d4 and 4-n-nonylphenol
      d4. Sample solutions were then centrifuged, and the supernatants purified using
      solid phase extraction with high polarity Carb/PSA composite fillers. Six target
      analytes were separated on a Waters ACQUITY BEH C18 column by gradient elution
      with methanol and 0.05% ammonium hydroxide in water as the mobile phase, and
      determined under multiple reactions monitoring mode. The limits of detection and
      quantitation, matrix effect, recovery and precision of the method were
      investigated. Results were linear in the concentration range 0.1-250 ug/L for all
      compounds of interest, with R2 > 0.9950. Limits of detection were in the range
      0.1-0.4 MUg/kg, and limits of quantitation were between 0.5 MUg/kg and 1.0
      MUg/kg. The mean recoveries for negative samples at three spiked concentrations
      were in the range 87.9%-102.4%, and the intra-day precision and inter-day
      precision were in the ranges 2.1-8.2% and 4.8-11.2%, respectively. This method is
      accurate and sensitive, and had good clean-up characteristics, which might apply
      to screening and quantitation of target bisphenols and alkylphenols in hotpot
      seasoning.

PMID- 29655725
TI  - N,S co-doped carbon dots based fluorescent "on-off-on" sensor for determination
      of ascorbic acid in common fruits.
AB  - A switchable sensor based on N and S co-doped carbon dots (N,S-CDs) was developed
      to determine ascorbic acid (AA) content in common fruits via fluorescence
      quenching of N,S-CDs by Fe3+ (off) and recovery by AA (on). TEM showed that the
      particle size was 2.35-7.95 nm with an average diameter of 5.12 nm. XPS and FTIR
      confirmed the presence of -OH, -COOH and -NH2 on N,S-CDs surface. UV-vis and FTIR
      revealed that the coordination of -COOH and -NH2 on N,S-CDs surface with Fe3+
      accounted for FL quenching, and the release of -NH2 from coordination complexes
      due to the reduction of Fe3+ by AA led to partly FL recovery. The sensor allowed
      detecting AA in the linear range of 10-200 MUmol/L with a LOD of 4.69 MUmol/L. AA
      contents in common fruits detected by the sensor were in good agreement with the
      reference method (P > 0.05), indicating a practical fluorescent sensor for AA
      detection in common fruits.

PMID- 29655726
TI  - Validated multiclass targeted determination of antibiotics in fish with high
      performance liquid chromatography-benchtop quadrupole orbitrap hybrid mass
      spectrometry.
AB  - High performance liquid chromatography, coupled with a benchtop Q-Exactive
      Orbitrap high-resolution mass spectrometer, was successfully applied for the
      determination of 24 target antibiotics (selected beta-lactams, tetracyclines,
      fluoroquinolones, sulfonamids, phenicols, macrolides, cephalosporins,
      lincosamides, diaminopyrimidine) in fish matrices. The Q-Exactive parameters were
      carefully studied to accomplish the best compromise between a suitable scan speed
      and selectivity, considering the restrictions associated with generic sample
      preparation methodology. Retention time, an exact mass with tolerance of 2 ppm
      and data-dependent MS2 spectra were the main identifiers. The method was
      validated through specificity, linearity, recovery, intra- and inter-day
      repeatability, decision limit (CCalpha) and detection capability (CCbeta),
      according to 2002/657/EC. The values of CCalpha and CCbeta ranged from 29.2 to
      36.8 and 32.5 to 48.9, respectively, while overall recovery ranged from 91.1 to
      105.6%. Fifty fish samples were analysed, showing the sporadic incidence of
      enrofloxacin, chlortetracycline, oxytetracycline, amoxicillin and trimethoprim,
      albeit below the maximum residual levels.

PMID- 29655727
TI  - Glycosaminoglycanomic profiling of human milk in different stages of lactation by
      liquid chromatography-tandem mass spectrometry.
AB  - Glycans in human milk serve several important biological functions that promote
      infant health. As kind of important glycans, glycosaminoglycans (GAGs) are a
      complex family of polyanionic carbohydrate, participating in a variety of
      critical physiological and pathological processes. In this study, the content and
      the detailed composition of human milk GAGs from Chinese mothers in different
      stages of lactation, based on a liquid chromatography-tandem mass spectrometry
      approach was investigated. The results showed that the GAG fraction in the human
      milk samples was very complex as it was composed of heparan sulfate, chondroitin
      sulfate, and hyaluronic acid. With lactation extending, the total amount of GAGs
      in human milk decreased. This study provided an important guide for the demands
      of GAGs during different stages of lactation. The results were also beneficial
      for studies on the composition and functional properties of infant formula.

PMID- 29655728
TI  - Influence of non-ionic emulsifier type on the stability of cinnamaldehyde
      nanoemulsions: A comparison of polysorbate 80 and hydrophobically modified
      inulin.
AB  - Cinnamaldehyde nanoemulsions were formulated to enable its application in an
      aqueous environment. The pure cinnamaldehyde nanoemulsions, stabilized by
      polysorbate 80 (at concentrations >0.5%), had both a higher stability and smaller
      droplet size, whereas the emulsions containing hydrophobically modified inulin
      (HMI) formed a colloidal dispersion with larger particle size. Incorporation of
      sunflower oil (SO) allowed postponement of Ostwald ripening for a sufficiently
      long period of time (at least 60 days). Cryo-SEM and droplet size analyses of the
      nanoemulsions emulsified by HMI revealed no significant changes during storage.
      Under these conditions, HMI as an emulsifier exhibited a powerful resistance to
      high salt contents (up to 2 M) and high thermal processing temperatures (90 
      degrees C). The surfactant type and SO content had no marked influence on the
      antimicrobial activity of the nanoemulsions. This study provides precious
      information for a commercial formulation of nanoemulsions with durable physical
      stability under severe stress conditions.

PMID- 29655729
TI  - In vitro effects of rebaudioside A, stevioside and steviol on porcine cytochrome
      p450 expression and activity.
AB  - The physiological effects of the Stevia-derived compounds, rebaudioside A,
      stevioside and steviol have been the focus of several studies due to their use as
      sweeteners in food. Despite that, little is known about their potential food-drug
      interactions. In the present study, IPEC-J2 cells and primary hepatocytes were
      used to investigate the effect of rebaudioside A, stevioside and steviol on
      cytochrome p450 (CYP) mRNA expression. Moreover, hepatic microsomes were used to
      investigate direct interactions between the compounds and specific CYP activity.
      In IPEC-J2 no changes in mRNA expression of CYP1A1 or CYP3A29 were observed with
      the Stevia-derived compounds. In primary hepatocytes all three tested compounds
      induced a significant increase in CYP3A29 expression. The tested compounds had no
      direct effect on specific CYP activity. In conclusion, rebaudioside A, stevioside
      and steviol induce only minor or no changes to the CYP expression and activity,
      and are not likely to cause food-drug interactions.

PMID- 29655730
TI  - NMR- and GC/MS-based metabolomic characterization of sunki, an unsalted fermented
      pickle of turnip leaves.
AB  - This study revealed the compositional characteristics of sunki, a traditional,
      unsalted, lactic acid-fermented pickle produced using turnip leaf in Kiso
      district, Japan. Comprehensive compositional analysis by two metabolomic
      approaches based on NMR and solid-phase microextraction-GC/MS methods was used to
      determine its chemical composition by annotating 54 water-soluble and 62 volatile
      compounds. Principal component analysis showed that samples had different
      compositions, depending on the agricultural processing factory and production
      year. This variation potentially resulted from the differences in the lactic acid
      bacterial community produced during the spontaneous fermentation of sunki and in
      the initial nutritional composition of the turnip leaf. Partial least squares
      regression revealed that the acetic acid level showed a strong positive
      correlation with pH (R = 0.810), in contrast to the negative correlations of
      lactic acid and ethanol levels (R =  -0.533 and -0.547). This indicated the
      crucial impact of acetic acid-related metabolism on acidification during sunki
      fermentation.

PMID- 29655731
TI  - Rapid detection and quantification of 2,4-dichlorophenoxyacetic acid in milk
      using molecularly imprinted polymers-surface-enhanced Raman spectroscopy.
AB  - We report the development of a molecularly imprinted polymers-surface-enhanced
      Raman spectroscopy (MIPs-SERS) method for rapid detection and quantification of a
      herbicide residue 2,4-dichlorophenoxyacetic acid (2,4-D) in milk. MIPs were
      synthesized via bulk polymerization and utilized as solid phase extraction
      sorbent to selectively extract and enrich 2,4-D from milk. Silver nanoparticles
      were synthesized to facilitate the collection of SERS spectra of the extracts.
      Based on the characteristic band intensity of 2,4-D (391 cm-1), the limit of
      detection was 0.006 ppm and the limit of quantification was 0.008 ppm. A simple
      logarithmic working range (0.01-1 ppm) was established, satisfying the
      sensitivity requirement referring to the maximum residue level of 2,4-D in milk
      in both Europe and North America. The overall test of 2,4-D for each milk sample
      required only 20 min including sample preparation. This MIPs-SERS method has
      potential for practical applications in detecting 2,4-D in agri-foods.

PMID- 29655732
TI  - Characterization and comparison of key aroma compounds in raw and dry porcini
      mushroom (Boletus edulis) by aroma extract dilution analysis, quantitation and
      aroma recombination experiments.
AB  - A study was carried out to determine and compare the key aroma compounds in raw
      and dry porcini mushroom (Boletus edulis). The volatile fractions were prepared
      by solvent-assisted flavor evaporation (SAFE), and aroma extract dilution
      analysis (AEDA) combined with gas chromatography-mass spectrometry (GC-MS) was
      employed to identify the odorants. Selected aroma compounds were quantitated and
      odor activity values (OAVs) were calculated revealing OAVs >= 1 for 12 compounds
      in raw porcini, among which 1-octen-3-one showed the highest OAV. In addition to
      compounds with eight carbon atoms, 3-methylbutanal, (E,E)-2,4-decadienal and
      (E,E)-2,4-nonadienal were also responsible for the unique aroma profile. In dry
      mushroom OAVs >= 1 were obtained for 20 odorants. Among them, 3
      (methylthio)propanal, 1-octen-3-one and pyrazines were determined as predominant
      odorants. Overall, drying increased complexity of volatile compounds, thus
      significantly changing the aroma profile of porcini, providing more desirable
      roasted and seasoning-like flavor and less grass-like and earthy notes.

PMID- 29655733
TI  - Particulate nanocomposite from oyster (Crassostrea rivularis) hydrolysates via
      zinc chelation improves zinc solubility and peptide activity.
AB  - An oyster protein hydrolysates-zinc complex (OPH-Zn) was prepared and
      investigated to improve zinc bioaccessibility. Zinc ions chelating with oyster
      protein hydrolysates (OPH) cause intramolecular and intermolecular folding and
      aggregation, homogeneously forming the OPH-Zn complex as nanoclusters with a Z
      average at 89.28 nm (PDI: 0.16 +/- 0.02). The primary sites of zinc-binding in
      OPH were carboxyl groups, carbonyl groups, and amino groups, and they were
      related to the high number of charged amino acid residues. Furthermore, formation
      of the OPH-Zn complex could significantly enhance zinc solubility both under
      specific pH conditions as well as during simulated gastrointestinal digestion,
      compared to the commonly used ZnSO4. Additionally, after digestion, either
      preserved or enhanced antioxidant activity of OPH was found when chelated with
      zinc. These results indicated that the OPH-Zn complex could be a potential
      functional ingredient with improved antioxidant bioactivity and zinc
      bioaccessibility.

PMID- 29655734
TI  - Toward water-solvation of rice proteins via backbone hybridization by casein.
AB  - Water insolubility is one of the major bottlenecks restricting the commercial
      availability of such food proteins as rice proteins (RPs), zein, etc. Here, we
      report that the structural hybridization of RPs and casein in a mass ratio of
      1:0.01 can boost the solubility of RPs to over 90%. A structural analysis
      demonstrated that the backbones of the RPs and casein were integrated in basic
      solution (pH 12.0) and folded together into higher structures with subsequent
      neutralization. The hybrid backbones obtained improved the molecules' resistance
      to structural changes during neutralization, and formed protein bodies with
      appreciable exposed polar groups, which may have been buried in the absence of
      casein. Morphological observations confirmed the formation of well-defined
      nanoscale particles with no visible aggregation. Both proteins also retained
      their intact primary peptide chains, thus significantly protecting the original
      nature of the plant and animal derivatives.

PMID- 29655735
TI  - Profiling, quantification and classification of cocoa beans based on chemometric
      analysis of carbohydrates using hydrophilic interaction liquid chromatography
      coupled to mass spectrometry.
AB  - Fifty-six cocoa bean samples from different origins and status of fermentation
      were analyzed by a validated hydrophilic interaction liquid chromatography
      electrospray ionization-time of flight-mass spectrometry (HILIC-ESI-TOF-MS)
      method. The profile of the low molecular weight carbohydrate (LMWC) was analyzed
      by high resolution and tandem mass spectrometry, which allowed the identification
      of mono-, di-, tri- and tetrasaccharides, sugar alcohols and iminosugars. This
      study provides, for the first time in a large set of samples, a comprehensive
      absolute quantitative data set for the carbohydrates identified in cocoa beans
      (fructose, glucose, mannitol, myo-inositol, sucrose, melibiose, raffinose and
      stachyose). Differences in the content of carbohydrates were observed between
      unfermented (range of 0.9-4.9 g/g DM) and fermented (range 0.1-0.5 g/g DM) cocoa
      beans. The use of multivariate statistical tools allowed the identification of
      biomarkers suitable for cocoa bean classification according to the status of
      fermentation, procedure of fermentation employed and number of days of
      fermentation.

PMID- 29655736
TI  - The molecularly imprinted polymer supported by anodic alumina oxide nanotubes
      membrane for efficient recognition of chloropropanols in vegetable oils.
AB  - A new route to synthesize a covalent interaction-based molecularly imprinted
      polymer (MIP) material for 3-chloro-1,2-propanediol (3-MCPD) inside the nanopores
      of anodic alumina oxide (AAO) is presented. A series of adsorption experiments
      showed MIP had good extraction capacity and selectivity for 3-MCPD. In order to
      evaluate the usability of the MIP nanotubes membrane, a method combining AAO@MIP
      membrane extraction with gas chromatography - mass spectrometry (GC-MS) detection
      was developed for determination of chloropropanols. The limits of detection for
      the proposed method were 0.072 and 0.13 ug.L-1, respectively, for 3-MCPD and 1,3
      DCP. The average recoveries of 3-MCPD and 1,3-DCP spiked oil samples at three
      concentrations (0.01, 0.05 and 0.1 mg.kg-1) were in the range of 75.6-101.0% with
      a RSD of 3.3-8.4%, indicating the method would be suitable for determination of
      chloropropanols in vegetable oils.

PMID- 29655737
TI  - Interactions of green coffee bean phenolics with wheat bread matrix in a model of
      simulated in vitro digestion.
AB  - Interactions of phenolics from green coffee bean flour (GCS) with the matrix of
      wheat bread have been studied employing direct (electrophoretic and
      chromatographic techniques) and indirect tests (nutrient digestibility).
      According to the chromatograms of digests, the antiradical activity of enriched
      bread was exhibited by free phenolics. An increase the area of chromatograms and
      some additional peaks observed for enriched bread may confirm some interactions
      of proteins with phenolics. The electrophoretic profile of these extracts showed
      that the band corresponding to a protein with molecular mass of 38 kDA had much
      higher intensity in enriched bread. Electrophoretic analysis of pellets remaining
      after digestion revealed GCS dose-dependent differences in bands corresponding to
      proteins with molecular masses of 52 kDa and 23 kDa. The relative digestibility
      of both starch and proteins was slightly decreased by addition of GCS; however,
      these changes did not exceed 10%, which justifies the use of this functional
      material.

PMID- 29655738
TI  - Excitation wavelength selection for quantitative analysis of carotenoids in
      tomatoes using Raman spectroscopy.
AB  - The difference in Raman spectra for different excitation wavelengths (532 nm, 785
      nm, and 1064 nm) was investigated to identify an appropriate wavelength for the
      quantitative analysis of carotenoids in tomatoes. For the 532 nm-excited Raman
      spectra, the intensity of the peak assigned to the carotenoid has no correlation
      with carotenoid concentration, and the peak shift reflects carotenoid composition
      changing from lycopene to beta-carotene and lutein. Thus, 532 nm-excited Raman
      spectra are useful for the qualitative analysis of carotenoids. For the 785 nm-
      and 1064 nm-excited Raman spectra, the peak intensity of the carotenoid showed
      good correlation with carotenoid concentration; thus, regression models for
      carotenoid concentration were developed using these Raman spectra and partial
      least squares regression. A regression model designed using the 785 nm-excited
      Raman spectra showed a better result than the 532 nm- and 1064 nm-excited Raman
      spectra. Therefore, it can be concluded that 785 nm is the most suitable
      excitation wavelength for the quantitative analysis of carotenoid concentration
      in tomatoes.

PMID- 29655739
TI  - Contribution to the study of rutin stability in the achenes of Tartary buckwheat
      (Fagopyrum tataricum).
AB  - Tartary buckwheat achenes are rich in rutin. However, its utilisation as a food
      is low due to the bitter taste of the products because of the transformation of
      rutin to quercetin. The aim of this study was to determine the stability of rutin
      and selected flavonoids, which are influenced by the different sample
      preparations exposing the achenes to higher temperatures (60  degrees C, 100 
      degrees C, and 140  degrees C), and also to determine the specificity of the
      rutin degrading enzymes in Tartary buckwheat. The achenes were directly extracted
      with methanol pre-extracted with hexane, or lyophilised before extraction. The
      rutin and quercetin contents were determined by HPLC. The rutin-degrading enzymes
      in Tartary buckwheat achenes were not inactivated after a heat treatment up to
      140  degrees C acting on them for three hours; neither to lyophilisation nor pre
      extraction with hexane. The rutin-degrading enzymes probably caused the
      deglycosylation of kaempferol-3-O-rutinoside, kaempferol-3-O-beta-d-glucoside and
      piceid. Rutin-degrading enzymes were inactivated with 100% methanol.

PMID- 29655740
TI  - Formation and characterization of zein-propylene glycol alginate-surfactant
      ternary complexes: Effect of surfactant type.
AB  - In this study, zein, propylene glycol alginate (PGA) and surfactant ternary
      complexes were fabricated by antisolvent co-precipitation method. Two types of
      surfactants (rhamnolipid and lecithin) were applied to generate zein-PGA
      rhamnolipid (Z-P-R) and zein-PGA-lecithin (Z-P-L) ternary complexes,
      respectively. Results showed that the surfactant types significantly affected the
      properties of ternary complexes. The formation of ternary complexes was mainly
      due to the non-covalent interactions such as hydrogen bonding, electrostatic
      interaction and hydrophobic interactions among zein, PGA and surfactants.
      Moreover, the thermal stability of ternary complexes was enhanced with increasing
      the levels of both surfactants. Notably, ternary complex dispersions exhibited
      better stability against pH from 2 to 8. Furthermore, a compact network structure
      was observed in Z-P-R ternary complex, while Z-P-L ternary complex remained the
      spherical structure. These findings would provide new insights into the
      development of novel delivery system and expand the options, when zein-based
      complexes were utilized under different environment conditions.

PMID- 29655741
TI  - Pb2+ and Hg2+ removal from polluted milk by di-acrylated Pluronic P123 hydrogels.
AB  - Milk is often polluted by heavy metal ions due to the growing environment
      pollution, but few methods have been developed to remove the heavy metal ions.
      Here a non-toxic sorbent, namely di-acrylated Pluronic P123 (P123-DA) hydrogel,
      was fabricated for removal of Hg2+ and Pb2+ from milk without impairing their
      nutritive contents. This hydrogel possessed high mechanical stress and maximum
      adsorption capacity of 35.2 and 53.9 mg/g for Pb2+ and Hg2+. The removal ratio of
      Pb2+ and Hg2+ by P123-DA hydrogel respectively reached 85.3% and 81.9% for the
      polluted whole milk while was individually 86.3% and 83.8% for the skim milk.
      Interestingly, the treatment by P123-DA hydrogel didn't significantly reduce the
      main nutritive contents in milk. Such hydrogel will be a recyclable, safe and
      effective tool for reuse of milk that polluted by heavy metal ions.

PMID- 29655742
TI  - Lactulose determination in UHT milk by CZE-UV with indirect detection.
AB  - Lactulose is not found naturally in milk, but it has been detected in small
      quantities in heated dairy products. It can therefore be used as an indicator of
      the severity of heat treatment for dairy products. This study proposes an
      alternative method for lactulose quantification in milk using capillary zone
      electrophoresis with ultraviolet detection (CZE-UV). The investigation used
      several Brazilian UHT milk samples, and various sample pretreatment methods and
      injection conditions were considered. Optimal separation results were achieved
      using Carrez clarification solutions. Low detection and quantification limits
      were obtained, and good precision and high recovery rates indicated the
      applicability of the method for analysis of milk. Due to matrix effects, single
      point standard addition was used for lactulose quantification. High lactulose
      concentrations (>1000 mg L-1) suggested that recirculation may have occurred
      during milk processing. The findings demonstrate that the CZE-UV method is a
      viable alternative for quality process control.

PMID- 29655743
TI  - Hyperspectral imaging for non-destructive prediction of fermentation index,
      polyphenol content and antioxidant activity in single cocoa beans.
AB  - The aim of the current work was to use hyperspectral imaging (HSI) in the
      spectral range 1000-2500 nm to quantitatively predict fermentation index (FI),
      total polyphenols (TP) and antioxidant activity (AA) of individual dry fermented
      cocoa beans scanned on a single seed basis, in a non-destructive manner.
      Seventeen cocoa bean batches were obtained and 10 cocoa beans were used from each
      batch. PLS regression models were built on 170 samples. The developed HSI
      predictive models were able to quantify three quality-related parameters with
      sufficient performance for screening purposes, with external validation R2 of
      0.50 (RMSEP = 0.27, RPD = 1.40), 0.70 (RMSEP = 34.1 mg ferulic acid g-1, RPD =
      1.77) and 0.74 (60.0 mmol Trolog kg-1, RPD = 1.91) for FI, TP and AA,
      respectively. The calibrations were subsequently applied at a single bean and
      pixel level, so that the distribution was visualised within and between single
      seeds (chemical images). HSI is thus suggested as a promising approach to
      estimate cocoa bean composition rapidly and non-destructively, thus offering a
      valid tool for food inspection and quality control.

PMID- 29655744
TI  - Immunomodulatory acidic polysaccharides from Zizyphus jujuba cv. Huizao: Insights
      into their chemical characteristics and modes of action.
AB  - Chinese jujube is commonly used in folklore medicine. This study aimed to examine
      the in vivo immunomodulatory activity of two acidic polysaccharides, HP1 and HP2,
      extracted and purified from Zizyphus jujuba cv. Huizao (which remains extensively
      unexplored). HP1 and HP2 had the same monosaccharide species and manganese
      contents, but differed in their molar rhamnose, arabinose, mannose, glucose,
      galactose and uronic acid contents (7.32 and 35.9%, as galacturonic acid), Mw
      (68.7 and 111 kDa, respectively), and contents of K, Cr, Cu, Zn, Pb and Ca. Both
      HP1 and HP2 could significantly (P < 0.05) increase spleen and thymus indices,
      promote serum hemolysin formation, enhance the phagocytic activity of macrophages
      and inhibit footpad edema of mice, with HP2 likely being a more consistent and
      potent immunomodulator. This study clearly demonstrates the potential of Z.
      jujuba cv. Huizao polysaccharides as immunomodulators and their associated
      chemical characteristics and working mechanisms.

PMID- 29655745
TI  - Study of the biochemical formation pathway of aroma compound 1-phenylethanol in
      tea (Camellia sinensis (L.) O. Kuntze) flowers and other plants.
AB  - After tea leaves, tea (Camellia sinensis) flowers are becoming a second tea plant
      resource because they contain not only functional metabolites similar to those
      found in tea leaves, but also predominant amounts of functional metabolites that
      only occur in tea leaves in small amounts. 1-Phenylethanol (1PE) is a predominant
      aroma compound found in tea flowers. A 1PE synthase in tea flowers was isolated,
      functionally characterized, and shown to have the highest catalytic efficiency
      for the conversion of acetophenone (AP). To determine why 1PE accumulates more in
      tea flowers than other plants, we compared their 1PE contents and used a stable
      isotope labeling method to elucidate the 1PE biosynthetic route. Supplementation
      with [2H8]l-phenylalanine and [2H5]AP suggested that most plants containing the
      enzyme/gene catalyzed the conversion of AP to 1PE. Furthermore, the availability
      of AP derived from l-phenylalanine was responsible for the difference in 1PE
      accumulation between tea flowers and other plants.

PMID- 29655746
TI  - Identification of pyruvate kinase as a novel allergen in whiteleg shrimp
      (Litopenaeus vannamei) by specific-IgE present in patients with shrimp allergy.
AB  - Food allergy is one of the most important health issues worldwide. In Taiwan,
      current literature suggests shrimps and crabs are the most common causes of food
      allergy, and are frequently associated with acute allergic reactions such as
      urticaria, atopic dermatitis, and asthma. However, knowledge regarding the shrimp
      allergens remains limited. Thus, there is an urgent need to establish
      comprehensive information for elucidating underlying triggers for food allergy.
      In this study, whiteleg shrimp (Litopenaeus vannamei) was used to evaluate the
      IgE-binding properties of various shrimp proteins to 7 allergic patients' sera by
      western blot. A 63 kDa protein was found in raw and cooked shrimp bound to
      specific-IgEs in 7 and 4 patients' sera, respectively. This protein was further
      identified as pyruvate kinase based on the proteomic mass spectrometry. This
      study identifies an important shrimp allergen unique to Taiwan and further
      testing and prevention measures might be implemented in the allergen analysis.

PMID- 29655747
TI  - Comparative performances of lactoferrin-loaded liposomes under in vitro adult and
      infant digestion models.
AB  - There remain gaps in our understanding of the fate of liposomes in the infant
      gastrointestinal tract, especially regarding essential proteins such as
      lactoferrin. Models in vitro that mirrored digestion in the stomach and intestine
      of infants and adults were used to explore the behaviour of lactoferrin-loaded
      liposomes. The liposomes behaved differently in these environments, with less
      hydrolysis of encapsulated lactoferrin under infant model conditions. Compared to
      the adult model (1000 +/- 66 MUM mL-1), fewer free fatty acids were released (500
      +/- 43 MUM mL-1) from liposomal bilayers and there was less alteration in
      functional groups of phospholipids membranes, based on pH and FTIR after infant
      model digestion. Particle tracking analysis and TEM supported the reduced damage
      of particle structure under infant model conditions. This work provides
      information on the stability of functional protein-loaded liposomes during
      digestion, and shows the potential of liposomes to be nutrient carriers in infant
      foods.

PMID- 29655748
TI  - 87Sr/86Sr isotopes in grapes of different cultivars: A geochemical tool for
      geographic traceability of agriculture products.
AB  - 87Sr/86Sr was determined on fresh red and white grapes, soils and rocks from
      three selected vineyards to verify the isotopic relationships between the fruit
      of the vine and geologic substrata of vineyards. 87Sr/86Sr were determined on
      sampled grapes of four different harvest years and different grape varieties, on
      bioavailable fraction of soils, on whole soils, and on bedrocks from the geo
      pedological substratum of the vineyards. The vineyards chosen for the
      experimental works belong to an organic farming winery and thus cultivation
      procedures were strictly controlled. Grapes were sampled during the harvests of
      four different but consecutive years with 87Sr/86Sr that does not change
      reflecting the values of the soil bioavailable fraction. No variations among
      grapes from different vine cultivars were observed. A strict isotope relationship
      with soil bio-available fraction was observed. These findings demonstrate the
      reliability of 87Sr/86Sr, even at a very small scale, for food products
      geographic origin assessment.

PMID- 29655749
TI  - Development of a statistical model to detect quality and storage conditions of
      Atlantic salmon.
AB  - The ever-increasing demand for fish as a food, has led to the development of new
      handling and packaging technologies resulting in premium quality fish products.
      In order to avoid frauds reaching the market, fish quality assurance methods need
      to be developed. In this study, two statistical models of biochemical processes
      that occur in Atlantic salmon during two weeks of storage at 0 and 4  degrees C
      were developed. These models were further used to detect salmon quality and its
      storage conditions. The biochemical processes were monitored using Nuclear
      Magnetic Resonance (NMR) spectroscopy and principal component analysis (PCA). The
      Soft Independent Modeling of Class Analogy (SIMCA) approach was applied to
      develop and evaluate the models. The fraud detection potential of the models was
      tested using samples of various quality and storage parameters. It was shown that
      the developed models are able to discriminate quality, time and temperature of
      stored Atlantic salmon.

PMID- 29655750
TI  - Structure-activity relationships between sterols and their thermal stability in
      oil matrix.
AB  - Structure-activity relationships between 20 sterols and their thermal stabilities
      were studied in a model oil system. All sterol degradations were found to be
      consistent with a first-order kinetic model with determination of coefficient
      (R2) higher than 0.9444. The number of double bonds in the sterol structure was
      negatively correlated with the thermal stability of sterol, whereas the length of
      the branch chain was positively correlated with the thermal stability of sterol.
      A quantitative structure-activity relationship (QSAR) model to predict thermal
      stability of sterol was developed by using partial least squares regression
      (PLSR) combined with genetic algorithm (GA). A regression model was built with R2
      of 0.806. Almost all sterol degradation constants can be predicted accurately
      with R2 of cross-validation equals to 0.680. Four important variables were
      selected in optimal QSAR model and the selected variables were observed to be
      related with information indices, RDF descriptors, and 3D-MoRSE descriptors.

PMID- 29655751
TI  - Isorenieratene interaction with human serum albumin: Multi-spectroscopic analyses
      and docking simulation.
AB  - Isorenierantene was reported to be an aromatic carotenoid and has become a food
      ingredient, mainly from smear cheese, which possesses special antioxidant ability
      and significant photoprotective effect. In this paper, the interaction of
      isorenieratene with human serum albumin (HSA) was explored and compared with that
      of nonaromatic carotenoids using multi-spectroscopic methods and docking
      simulations. The results suggested isorenieratene could bind to HSA through a
      static quenching mechanism. The binding processes were spontaneous and
      exothermic, and the binding between isorenieratene and HSA was mainly driven by
      hydrophobic forces and electrostatic attraction. Synchronous fluorescence
      spectroscopy, Fourier transform infrared (FT-IR) spectroscopy, and surface
      enhanced Raman scattering (SERS) experiments showed isorenieratene may change the
      secondary structure of HSA and the micro-environment of its amino acids.
      Additionally, isorenieratene showed higher stability during the binding process
      than did nonaromatic carotenoids. Docking simulation indicated isorenieratene may
      bind to HSA at site II.

PMID- 29655752
TI  - Systematic evaluation of phenolic compounds and protective capacity of a new
      mulberry cultivar J33 against palmitic acid-induced lipotoxicity using a
      simulated digestion method.
AB  - This research aimed to investigate the protective effects of a new mulberry
      cultivar J33 with simulated gastrointestinal digestion against palmitic acid (PA)
      induced lipotoxicity. LC-MS analysis revealed that the contents of four flavonoid
      glycosides (quercetin rhamnosylhexoside hexoside, quercetin rhamnosylhexoside,
      quercetin hexoside, kaempferol rhamnosylhexoside) increased after digestion.
      Besides, mulberry digest (MBD) at 0.5-2 mg/mL significantly reduced PA-induced
      lipotoxicity in human hepatocytes, while mulberry extract without digestion (MBE)
      showed no protection. Further investigations demonstrated that the protection of
      MBD was attributed to two aspects. On the one hand, MBD could attenuate PA
      induced oxidative stress by suppressing ROS accumulation, regulating
      intracellular glutathione and ameliorating mitochondrial dysfunction. On the
      other hand, MBD could promote PA incorporation into inert triglycerides (TG) to
      deal with the acute lipid overload, reducing the lipotoxicity caused by PA.
      Overall, our research might provide a new perspective of mulberry cultivar J33 in
      ameliorating non-alcoholic fatty liver disease (NAFLD).

PMID- 29655753
TI  - Detection of Fe(III)EDTA by using photoluminescent carbon dot with the aid of F-
      ion.
AB  - Iron(III) ethylenediaminetetraacetate (Fe(III)EDTA) is widely used in iron
      fortification for reducing iron deficiency, and its determination is urgently
      needed. The present work developed a fluorescent method to straightforwardly
      determine Fe(III)EDTA by using photoluminescent carbon dots (C-dots) with the aid
      of F- ions as the masking agent of free Fe3+ ions. In the presence of F- ions,
      only Fe(III)EDTA selectively quenched the photoluminescence of C-dots, and both
      Fe3+ and Fe2+ as well as other carboxylic acids have no effect on the emission of
      C-dots. The sensing mechanism was attributed to the ligand-tailored electron
      transfer process from C-dots to Fe3+. Under optimum conditions, this method
      showed a linear calibration plot over the Fe(III)EDTA range of 1.0-200 MUmol L-1
      and a detection limit of 0.4 MUmol L-1. The proposed method was successfully
      applied to determine Fe(III)EDTA in real samples with acceptable recoveries of
      spikes (95%-110%) and repeatability (RSD, 4.2%-9.5%).

PMID- 29655754
TI  - Green and fast determination of the alcoholic content of wines using thermal
      infrared enthalpimetry.
AB  - An innovative use of thermal infrared enthalpimetry (TIE) is proposed for the
      determination of alcoholic content of red and white wines. Notwithstanding the
      presence of ethanol in beverages, absolute ethanol was added directly to wines,
      and the temperature rise caused by the heat of dilution was monitored using an
      infrared camera. Analytical signals were obtained in only 10 s for four samples
      simultaneously, and a calibration curve was constructed with hydroalcoholic
      reference solutions. A linear calibration curve was obtained from 3.0 to 18.0%
      (v/v) ethanol (R2 = 0.9987). The results showed agreement ranging from 98.2 to
      104.0% with 942.06 and 969.12 methods of AOAC. Organic compounds (e.g., sugar)
      did not interfere in the determinations. The proposed method provided fast
      results, with a throughput of 480 samples per hour and negligible energy
      consumption (0.001 kWh). In addition, the consumption of reagents was reduced
      when compared with conventional method fulfilling green analytical chemistry
      requirements.

PMID- 29655755
TI  - Concentration of natural aroma compounds from fruit juice hydrolates by
      pervaporation in laboratory and semi-technical scale. Part 1. Base study.
AB  - The first article of a two-article series presents pervaporation (PV) of volatile
      aroma compounds from fruit juice hydrolates (plum, apple, blackcurrant and
      cherry). The purpose of this research was to evaluate the effectiveness of fruit
      juice hydrolates separation on a laboratory scale (inert gas flow pervaporation
      system) and semi-technical (vacuum pervaporation system) by means of
      pervaporation. To create precise matrices for hydrolates before and after
      pervaporation for each of the separated systems, solid phase microextraction
      (SPME) technique and the gas chromatography-mass spectrometry (GC-MS) was
      applied. Sensory analysis confirmed improvement of aroma note of concentrated
      permeates as compared to feed hydrolates solutions. The results indicated that
      pervaporation may be applied in condensing aromatic water or fruit juice
      hydrolate, which may significantly enhance product quality and lengthen shelf
      life.

PMID- 29655756
TI  - Effects of ocean warming and acidification, combined with nutrient enrichment, on
      chemical composition and functional properties of Ulva rigida.
AB  - Ulva is increasingly viewed as a food source in the world. Here, Ulva rigida was
      cultured at two levels of temperature (14, 18  degrees C), pH (7.95, 7.55,
      corresponding to low and high pCO2), and nitrate conditions (6 MUmol L-1, 150
      MUmol L-1), to investigate the effects of ocean warming, acidification, and
      eutrophication on food quality of Ulva species. High temperature increased the
      content of each amino acid. High nitrate increased the content of all amino acids
      except aspartic acid and cysteine. High temperature, pCO2, and nitrate also
      increased the content of most fatty acids. The combination of high temperature,
      pCO2, and nitrate increased the swelling capacity, water holding capacity, and
      oil holding capacity by 15.60%, 7.88%, and 16.32% respectively, compared to the
      control. It seems that the future ocean environment would enhance the production
      of amino acid and fatty acid as well as the functional properties of Ulva
      species.

PMID- 29655757
TI  - Fucoxanthin bioavailability from fucoxanthin-fortified milk: In vivo and in vitro
      study.
AB  - Our previous study reported the improved stability of fucoxanthin (FX) fortified
      in whole milk (WM) and skimmed milk (SM). In this study, in vivo and in vitro FX
      bioavailability were investigated using FX-fortified milk (FX-SM and FX-WM) and
      microalga Phaeodactylum tricornutum biomass (Pt-powder). Organ tissue
      accumulation of FX and its metabolites (FXOH: fucoxanthinol, AXA:
      amarouciaxanthin A) after repeated oral administration was in the following
      order: FX-SM > FX-WM > Pt-powder. In vivo pharmacokinetic study with a single
      oral administration also demonstrated that the absorption of FXOH and AXA was the
      highest for FX-SM. To reinforce the in vivo results, in vitro-simulated digestion
      and Caco-2 cell uptake assays were performed, which revealed that FX-SM showed
      the highest FX bioaccessibility (release from food matrices) and cellular uptake
      efficiency of FX and FXOH. In conclusion, skimmed milk was validated as an
      excellent food matrix for FX application in terms of stability and
      bioavailability.

PMID- 29655758
TI  - Characterisation of the antioxidant peptide AEEEYPDL and its quantification in
      Spanish dry-cured ham.
AB  - Bioactive peptides derived from food matrices are currently a subject of
      intensive research, due to the multiple health benefits they can exert in the
      human body. However, the small size and low abundance of these peptides in
      complex matrices as well as the effect of food processing and gastrointestinal
      digestion on their structure, sequence, and functionality, are important
      challenges. Spanish dry-cured ham has been reported as a good and natural source
      of bioactive peptides mainly showing antihypertensive and antioxidant activities.
      In this work, the antioxidant peptide AEEEYPDL, identified from 9 months of
      curing dry-cured ham, showed good resistance to different heat treatments and
      salt contents. The bioactivity of the peptide significantly decreased after
      simulated gastrointestinal digestion. An optimised multiple reaction monitoring
      methodology was able to quantify the peptide AEEEYPDL at a concentration of 0.148
      fg per g of dry-cured ham, despite the existing challenges in the quantification
      of bioactive peptides from complex matrices.

PMID- 29655759
TI  - Determination of 21 antibiotics in sea cucumber using accelerated solvent
      extraction with in-cell clean-up coupled to ultra-performance liquid
      chromatography-tandem mass spectrometry.
AB  - An accelerated solvent extraction (ASE) with in-cell clean-up method coupled to
      ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was
      developed to determine 21 antibiotics in sea cucumber. The analytes include 10
      sulfonamides, 4 fluoroquinolones, 3 amphenicols, 2 beta-lactams, 1 lincosamide
      and trimethoprim. Optimal parameters of ASE method were obtained at 80  degrees
      C, 1 static cycle of 5 min with methanol/acetonitrile (1/1, v/v) using 2 g of C18
      as adsorbent. Recoveries at 50.1-129.2% were achieved with RSD under 20%. Method
      detection limits ranged from 0.03 to 2.9 MUg kg-1. Compared to the reported
      ultrasound-assisted extraction method, the proposed method offered comparable
      extraction efficiency for sulfonamides from sea cucumber, but higher for other
      categories of antibiotics. This validated method was then successfully applied to
      sea cucumber samples and 9 antibiotics were detected with the highest
      concentration up to 57.7 MUg kg-1 for norfloxacin.

PMID- 29655760
TI  - Psidium cattleianum fruits: A review on its composition and bioactivity.
AB  - Psidium cattleianum Sabine, commonly known as araca, is a Brazilian native fruit,
      which is very juicy, with sweet to sub acid pulp and a spicy touch. The fruit can
      be eaten fresh or processed into juice, jellies and ice creams. Aracas are source
      of vitamin C, minerals, fatty acids, polysaccharides, volatile compounds,
      carotenoids and phenolic compounds, which can provide nutrients and phytochemical
      agents with different biological functions. Different pharmacological studies
      demonstrate that P. cattleianum exerts antioxidant, antidiabetic,
      anticarcinogenic, antimicrobial, anti-inflammatory and antiaging effects. Thus,
      this article aims to review the chemical composition and biological effects
      reported for araca fruit in the last years.

PMID- 29655761
TI  - The relationship between culinary skills and eating behaviors: Challenges and
      opportunities for parents and families.
AB  - Unhealthy dietary intake among American children and adults is of great concern
      to public health practitioners, nutritional scientists, and child development
      experts. Cooking skills are related to healthier dietary intake among Americans
      of all ages, but remain a substantial barrier for many parents who want to serve
      healthy meals for their families at home. Culinary education interventions are
      effective solutions for many parents who do not know how to cook, but issues with
      participation bias mean that these programs are not effective solutions for all
      individuals. The food industry should develop solutions to help those parents for
      whom learning cooking skills is not an option - specifically through the
      development of healthier pre-assembled or prepared foods that do not require
      cooking skills to make. In the future, the research community should also strive
      to collect comprehensive population-based data on the state of cooking skills in
      the United States.

PMID- 29655762
TI  - Amateur endurance triathletes' performance is improved independently of volume or
      intensity based training.
AB  - The aim of the present research was to compare the effects in swimming and
      running performance, horizontal jump test, autonomic modulation, and body
      composition of four training weeks with emphasis on volume versus intensity in
      moderate trained triathletes. Thirty-two amateur triathletes (20 males and 12
      females) were randomly divided in three different groups that performed 6
      training session per week: Intensity (INT): training focused on performs
      intensity training Volume (VOL): training focused on performs volume training;
      and Control (CON): physical active group with no periodized training. Body
      composition, heart rate variability, horizontal jump test, swimming and 2000 m
      running test were tested before and after the training period. There were no
      significant differences between INT and VOL in running test. Furthermore, both
      INT and VOL training groups improved 50 m (p: 0.046 and 0.042 respectively) and
      400 m (p: 0.044 and 0.041 respectively) swimming performance. Moreover, there
      were no significant differences among groups in any moment in HRV variables. No
      significant difference was observed for horizontal jump test and body composition
      between the INT and VOL group at any time. According to the results of the
      present study, four weeks of training with either high intensity or volume
      results to similar adaptations in endurance, horizontal jump test and body
      composition parameters in amateur triathletes.

PMID- 29655764
TI  - Anomalous Pulmonary Venous Drainage and Pulmonary Vein Stenosis.

PMID- 29655763
TI  - Sleeping oxygen saturation, rapid eye movement sleep, and the adaptation of
      postprandial metabolic function in insulin sensitive and resistant individuals
      without diabetes.
AB  - AIMS: Sleeping oxygen saturation (SaO2) and sleep stage duration have been linked
      with prediabetic alterations but the pathogenic pathways are not well understood.
      This study of insulin sensitive and resistant adults examined the effect on
      postprandial metabolic regulation of repeated mixed-meal challenges of different
      carbohydrate loading. The aim was to examine whether the relationship between
      lower sleeping oxygen saturation (SaO2) and poorer fasting and postprandial
      metabolic function may be linked with reduced slow wave sleep (SWS) and rapid eye
      movement (REM) duration, independent of age, sex and total adiposity. METHODS:
      The 24 men and women, aged 25-54 years, had no diabetes or other diagnosed
      conditions, were evaluated with polysomnography to derive indices of SaO2 and
      sleep architecture. In addition, an OGTT and two 14-h serial mixed-meal tests
      were administered over 3 successive in-patient days. The carbohydrate content of
      the mixed-meals was manipulated to compare a standard-load day with a double-load
      day (300 vs. 600 kcal/meal). Quantitative modeling was applied to derive beta
      cell glucose sensitivity (beta-GS), early insulin secretion rate sensitivity
      (ESRS), and total postprandial insulinemia (AUCINS). RESULTS: Analyses showed
      that, for the 14-h tests, the SaO2 relationship with metabolic outcomes was
      associated significantly with percent time spent in REM but not SWS, independent
      of age, sex and total adiposity. Specifically, indirect pathways indicated that
      lower SaO2 was related to shorter REM duration, and shorter REM was respectively
      associated with higher beta-GS, ESRS, and AUCINS for the 300- and 600-load days
      (300 kcal/meal: beta = -8.68, p < .03, beta = -8.54, p < .002, and beta = -10.06,
      p < .008; 600 kcal/meal: beta = -11.45, p < .003, beta = -11.44, p < .001, and
      beta = -11.00, p < .03). CONCLUSION: Sleeping oxygen desaturation and diminished
      REM duration are associated with a metabolic pattern that reflects a compensatory
      adaptation of postprandial insulin metabolism accompanying preclinical diabetic
      risk.

PMID- 29655765
TI  - Health Professionals, Organizations and the Health System: Making What Is
      Socially Advisable Individually Attractive.

PMID- 29655766
TI  - Mechanical Chest Compressions and Traumatic Complications in Out-of-hospital
      Cardiac Arrest. Is There a Price to Pay?

PMID- 29655767
TI  - Correction in Article by Vaglimi et al. "2017 ESC Focused Update on Dual
      Antiplatelet Therapy in Coronary Artery Disease Developed in Collaboration with
      EACTS", Rev Esp Cardiol. 2018;71:42.e1-e58.

PMID- 29655768
TI  - Cell-free DNA and Microvascular Damage in ST-segment Elevation Myocardial
      Infarction Treated With Primary Percutaneous Coronary Intervention.
AB  - INTRODUCTION AND OBJECTIVES: Cell-free DNA (cfDNA) in ST-segment elevation
      myocardial infarction might originate from hyperactivated leukocytes at the
      coronary lesion. Our aim was to investigate the relationship between cfDNA and
      coronary reperfusion. METHODS: We studied 116 patients treated with primary
      angioplasty using thrombus aspiration. Coronary (during aspiration) and
      peripheral (at the end of the procedure) blood samples were drawn for cfDNA, as
      well as high-sensitivity troponin T and myeloperoxidase quantification. The
      primary endpoint was no ST-segment resolution (STR) (>= 70%) and the secondary
      endpoint was lack of final Thrombolysis In Myocardial Infarction flow 3 (TIMI 3).
      RESULTS: ST-segment resolution was achieved in 51 (44%) patients and TIMI 3 flow
      in 97 (84%). Patients without STR and TIMI 3 flow had a smaller peripheral
      coronary cfDNA gradient (P = .02 and P = .04 respectively). A small cfDNA
      gradient (< 1.82 ng/mL) was associated with a higher rate of no STR (65% vs 30%;
      P = .001) and lack of TIMI 3 flow (21% vs 3%; P = .05). After multivariable
      adjustment, the small cfDNA gradient was predictive of no STR (OR, 4.50; 95%CI,
      1.60-12.62; P = .004), while there was a nonsignificant trend for final TIMI 3
      flow (P = .14). Cell-free DNA levels did not correlate with troponin T or
      myeloperoxidase. CONCLUSIONS: A small peripheral-coronary cfDNA gradient, as an
      expression of high coronary cfDNA burden, is associated with no STR in acute
      myocardial infarction. Intracoronary cfDNA might reflect neutrophil activation.
      Whether this phenomenon contributes to thrombus aspiration failure requires
      further study.

PMID- 29655769
TI  - Near infrared optical biosensor based on peptide functionalized single-walled
      carbon nanotubes hybrids for 2,4,6-trinitrotoluene (TNT) explosive detection.
AB  - A near infrared (NIR) optical biosensor based on peptide functionalized single
      walled carbon nanotubes (SWCNTs) hybrids for 2,4,6-trinitrotoluene (TNT)
      explosive detection was developed. The TNT binding peptide was directly anchored
      on the sidewall of the SWCNTs using the pi-pi interaction between the aromatic
      amino acids and SWCNTs, forming the peptide-SWCNTs hybrids for near infrared
      absorption spectra measurement. The evidence of the morphology of peptide-SWCNTs
      hybrids was obtained using atomic force microscopy (AFM). The results
      demonstrated that peptide-SWCNTs hybrids based NIR optical biosensor exhibited
      sensitive and highly selective for TNT explosive determination, addressing a
      promising optical biosensor for security application.

PMID- 29655770
TI  - A high-throughput screening assay for pyruvate carboxylase.
AB  - Pyruvate carboxylase (PC) catalyzes the conversion of pyruvate to oxaloacetate
      (OAA), an important metabolic reaction in a wide range of organisms. Small
      molecules directed against PC would enable detailed studies on the metabolic role
      of this enzyme and would have the potential to be developed into pharmacological
      agents. Currently, specific and potent small molecule regulators of PC are
      unavailable. To assist in efforts to find, develop, and characterize small
      molecule effectors of PC, a novel fixed-time assay has been developed based on
      the reaction of OAA with the diazonium salt, Fast Violet B (FVB), which produces
      a colored adduct with an absorbance maximum at 530 nm. This fixed time assay is
      reproducible, sensitive and responsive to known effectors of Rhizobium etli PC,
      Staphylococcus aureus PC, and Listeria monocytogenes PC, and is highly amenable
      to high-throughput screening. The assay was validated using a plate uniformity
      assessment test and a pilot screen of a library of 1280 compounds. The results
      indicate that the assay is suitable for screening small molecule libraries to
      find novel small molecule effectors of PC.

PMID- 29655771
TI  - Iodinated Contrast Media Allergy in Patients Hospitalized for Investigation of
      Chest Pain.
AB  - BACKGROUND: Iodinated contrast media (ICM) allergy may entail severe adverse
      events in patients who undergo percutaneous coronary intervention (PCI).
      Premedication protocols and low-osmolality contrast media have been thought to
      improve the outcomes of these individuals. OBJECTIVE: The objective of this study
      was to assess the prevalence and severity of allergic reactions during PCI in
      patients admitted for investigation of chest pain. METHODS: This is a
      retrospective analysis of 13,652 patients who were hospitalized with chest pain
      during the years 2010-2016, at the Department of Internal Medicine, Meir Medical
      Center. Patient records were screened for diagnosis of prior ICM allergy. Primary
      outcomes were: (1) records of previous allergy to ICM, (2) administration of
      antiallergic premedication, and (3) allergic reactions to the ICM during the
      procedure. RESULTS: Nine hundred thirty-one individuals without prior ICM allergy
      were referred for PCI, of whom 2 had minor allergic reactions. Previously
      diagnosed ICM allergy was recorded for 216 subjects (mean age 65.5 +/- 10 years,
      42% males). Of these, 32 were referred to in-hospital PCI. Premedication was
      administered in 10 cases only with no documented rationale for not treating the
      other 22. Only one of the pretreated patients experienced a reaction attributed
      to allergy, showing no statistical advantage for premedication. No mortality was
      documented in the 30 days after PCI among the patients with known ICM allergy.
      CONCLUSIONS: PCI did not induce substantial allergic reactions to ICM in patients
      with a previously diagnosed allergy. This study did not demonstrate an advantage
      for premedication.

PMID- 29655772
TI  - Predicting Chronic Spontaneous Urticaria Symptom Return After Omalizumab
      Treatment Discontinuation: Exploratory Analysis.
AB  - BACKGROUND: Omalizumab is highly effective in controlling chronic spontaneous
      urticaria (CSU) symptoms; however, patients can experience symptom return on
      treatment discontinuation. Pivotal clinical trials have identified 2 categories
      of patients who experience symptom return: rapid and slow. OBJECTIVE: The
      objective of this study was to identify potential predictors of the speed of
      symptom return after stopping omalizumab treatment. METHODS: Phase III randomized
      controlled trial (RCT) data from ASTERIA I (n = 319; 6 * 4 weekly injections of
      omalizumab 75, 150, 300 mg or placebo; NCT01287117) and ASTERIA II (n = 323; 3 *
      4 weekly injections of omalizumab 75, 150, 300 mg, or placebo; NCT01292473) were
      pooled to identify predictors of symptom return after stopping omalizumab
      treatment (16-week follow-up). The least absolute shrinkage and selection
      operator regularization regression model was used to select predictive variables,
      and relapse probability was represented using heatmap visualizations. Model
      accuracy was tested using data from the GLACIAL phase III RCT (n = 336; 6 * 4
      weekly injections of omalizumab 300 mg or placebo; NCT0126493). RESULTS: Of 746
      variables assessed, 2 were selected by the model as predictors of symptom return:
      baseline urticaria activity score over 7 days (UAS7) and early area above the
      curve (AAC; determined by plotting the UAS7 scores across time points). Results
      suggest that high baseline UAS7 and low UAS7 AAC (slow decrease of symptoms)
      indicate a higher probability of rapid symptom return than low baseline UAS7 and
      high UAS7 AAC. CONCLUSIONS: These results suggest that the probability of rapid
      symptom return in patients with CSU who discontinue treatment with omalizumab can
      be estimated based on baseline UAS7 and early treatment response.

PMID- 29655773
TI  - Successful rapid oral clindamycin desensitization in a pediatric patient.

PMID- 29655774
TI  - Twenty Years' Experience with Anaphylaxis-Like Reactions to Local Anesthetics:
      Genuine Allergy is Rare.
AB  - BACKGROUND: Anaphylaxis-like reactions occur within minutes after the application
      of local anesthetics (LA), most commonly during dental interventions. Impressive
      symptoms including respiratory distress or loss of consciousness frequently give
      rise to a suspicion of allergy and may prompt patients and treating physicians to
      refuse future LA injections. OBJECTIVE: Nonallergic mechanisms are responsible
      for the majority of LA-induced immediate-type reactions. In view of the
      preponderance of nonallergic reactions, the question arises whether genuine LA
      allergy may be missed during routine testing procedures. METHODS: We
      retrospectively evaluated clinical data and test results from patients referred
      to our allergy clinic within the past 20 years for diagnostic workup of LA
      induced immediate-type reactions. RESULTS: Of 402 evaluated patients, 29 had an
      episode of acute urticaria within 30 minutes after LA injections, and the
      remaining 373 had a history of mainly subjective cutaneous, respiratory,
      cardiovascular, and neurological complaints. Of the patients reporting urticaria
      with or without angioedema, 14 were diagnosed with a spontaneous episode of
      urticaria, 13 had allergic or nonallergic reactions to other agents, and 2 had
      IgE-mediated LA allergy. LA allergy was definitely excluded by 771 subcutaneous
      provocation tests with skin test negative LA, thereby demonstrating the high
      predictive value of negative intradermal testing. CONCLUSIONS: Skin testing and
      provocative LA challenge are useful to exclude LA allergy, and this testing
      procedure seems to be appropriate to identify the extremely rare cases with IgE
      mediated LA allergy.

PMID- 29655775
TI  - Relationship between water intake and skeletal muscle mass in elderly Koreans: A
      nationwide population-based study.
AB  - OBJECTIVES: The purposes of this study were to evaluate the correlation between
      sarcopenia and water intake and investigate lack of daily water intake in the
      presence of sarcopenia in an elderly population. METHODS: Data from 3656
      participants (1582 men and 2074 women) were analyzed using the Korea National
      Health and Nutrition Examination Survey. Sarcopenia was defined in accordance
      with the criteria of the Asia Working Group for Sarcopenia. Water intake was
      assessed using the dietary water adequacy ratio and was calculated by dividing
      the daily water intake from fluid by the recommended daily amount of 1000 mL in
      men and 900 mL in women. RESULTS: Water intake from food (g/d and cup/d) and
      dietary water adequacy ratio (mL) were significantly lower in the sarcopenia
      group (757.8 g, 890.1 g, and 0.74 mL in men; 511.9 g, 757.8 g, and 0.70 mL in
      women, respectively) than in the non-sarcopenia group (878.4 g, 1015.1 g, and
      0.81 mL in men; 581.3 g, 790.5 g, 0.74 mL in women, respectively). In elderly
      men, the odds ratio of sarcopenia in the lowest quartile increased to 1.47
      (range, 1.13-1.91) in Model 2 compared with that in the highest quartile. In
      elderly women, the odds ratio of sarcopenia in the lowest quartile increased to
      1.50 (range, 1.08-2.08) in Model 2 compared with that in the highest quartile.
      CONCLUSIONS: The prevalence of sarcopenia in the elderly population was related
      to inadequate dietary water intake after adjusting for covariates. Adequate water
      intake in the elderly should be recommended to prevent dehydration-related
      complications, including sarcopenia.

PMID- 29655776
TI  - Association between dietary inflammatory index and Hodgkin's lymphoma in an
      Italian case-control study.
AB  - OBJECTIVES: The components of a diet can modulate inflammation and may have an
      effect on the development of Hodgkin's lymphoma (HL). Little is known about the
      inflammatory potential of diet in relation to HL. METHODS: Data from an Italian
      multicenter case-control study that was conducted between 1992 and 2008 were used
      to estimate the relation between a dietary inflammatory index (DII(r)) and the
      risk of HL. The data included 179 cases with incident, histologically confirmed
      HL and 186 control cases who were hospitalized for acute non-neoplastic diseases.
      The DII was computed on the basis of a validated, 78-item, food-frequency
      questionnaire. Logistic regression models were used to estimate odds ratios that
      were adjusted for age, sex, total energy intake, center, body mass index, years
      of education, tobacco use, and alcohol consumption. RESULTS: No significant
      association was observed between an increasing DII and the risk of HL when used
      either as a continuous or categorical variable. The multivariate odds ratio for
      the highest versus the lowest DII tertile was 1.20 (95% confidence interval: 0.71
      2.04). Similarly, no positive association was observed when analyses were carried
      out by different strata of selected covariates. CONCLUSIONS: These results do not
      support the hypothesis that the inflammatory potential of a diet plays a major
      role in the development of HL.

PMID- 29655777
TI  - Body composition evaluated by body mass index and bioelectrical impedance vector
      analysis in women with rheumatoid arthritis.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is a complex inflammatory disease that
      modifies body composition. Although body mass index (BMI) is one of the clinical
      nutrition tools widely used to assess indirectly nutritional status, it is not
      able to identify these body alterations. Bioelectrical Vector Analysis (BIVA) is
      an alternative method to assess hydration and body cell mass of patients with
      wasting conditions. OBJECTIVE: To investigate the differences in nutrition status
      according to BMI groups (normal, overweight and obesity) and BIVA classification
      (cachectic and non-cachectic) in women with RA. METHODS: Women with confirmed
      diagnosis of RA were included from January 2015 to June 2016. Whole-body
      bioelectrical impedance was measured using a tetrapolar and mono-frequency
      equipment. Patients were classified according to BMI as: low body weight (n = 6,
      2.7%), normal (n = 59, 26.3%), overweight (n = 88, 39.3%) and obese (n = 71,
      31.7%), and each group was divided into BIVA groups (cachectic 51.8% and non
      cachectic 48.2%). RESULTS: A total of 224 RA patients were included, with mean
      age 52.7 years and median disease duration of 12 years. Significant differences
      were found in weight, arm circumference, waist, hip, resistance/height,
      reactance/height and erythrocyte sedimentation rate among all BMI groups.
      However, serum albumin levels were significantly different between cachectic and
      non-cachectic patients independently of BMI. In all BMI categories, cachectic
      groups had lower reactance and phase angle than non-cachectic subjects.
      CONCLUSION: RA patients with normal or even high BMI have a significantly lower
      muscle component. Evaluation of body composition with BIVA in RA patients could
      be an option for cachexia detection.

PMID- 29655778
TI  - Self-reported weight and predictors of missing responses in youth.
AB  - OBJECTIVE: The aims of the present manuscript are to analyse self-reported data
      on weight, including the missing data, from the 2014 Scottish Health Behaviour in
      School-Aged Children (HBSC) Study, and to investigate whether behavioural factors
      related with overweight and obesity, namely dietary habits, physical activity and
      sedentary behaviour, are associated with weight non-response. RESEARCH METHODS &
      PROCEDURES: 10839 11-, 13- and 15-year-olds participated in the cross-national
      2014 Scottish HBSC Study. Weight missing data was evaluated using Little's
      Missing Completely at Random (MCAR) test. Afterwards, a fitted multivariate
      logistic regression model was used to determine all possible multivariate
      associations between weight response and each of the behavioural factors related
      with obesity. RESULTS: 58.9% of self-reported weight was missing, not at random
      (MCAR p < 0.001). Weight was self-reported less frequently by girls (19.2%) than
      by boys (21.9%). Participants who reported low physical activity (OR 1.2, p <
      0.001), low vegetable consumption (OR 1.24, p < 0.001) and high computer gaming
      on weekdays (OR 1.18, p = 0.003) were more likely to not report their weight.
      CONCLUSIONS: There are groups of young people in Scotland who are less likely to
      report their weight. Their weight status may be of the greatest concern because
      of their poorer health profile, based on key behaviours associated with their non
      response. Furthermore, knowing the value of a healthy weight and reinforcing
      healthy lifestyle messages may help raise youth awareness of how diet, physical
      activity and sedentary behaviours can influence weight.

PMID- 29655779
TI  - Postprandial glucose and insulin response to a high-fiber muffin top containing
      resistant starch type 4 in healthy adults: a double-blind, randomized, controlled
      trial.
AB  - OBJECTIVES: VERSAFIBETM 2470 resistant starch (RS) is an RS type 4 that is
      derived from high-amylose maize starch,70% total dietary fiber (TDF; AOAC method
      2009.01). This was a randomized, double-blind, crossover study to evaluate the
      postprandial blood glucose and insulin responses of healthy adults (n = 28) after
      the consumption of a muffin top made with VERSAFIBETM 2470 RS (11.6 g TDF fiber
      muffin top) or a control muffin top (0.9 g TDF). METHODS: The muffin tops were
      matched for weight, total carbohydrate, sugars, protein, and fat. During each
      treatment period, subjects consumed a standard evening meal, fasted for 12 h, and
      arrived at the study clinic the following morning. Serum glucose, serum insulin,
      and capillary glucose were measured at 0, 15, 30, 45, 60, 90, and 120 min after
      muffin top consumption. The subjects completed a 7-d washout period between
      treatments. RESULTS: The consumption of the fiber muffin top resulted in a
      significant 33% reduction in postprandial serum glucose incremental area under
      the curve from 0 to 120 min and an 8% decrease in maximum glucose concentration
      versus the control muffin (P = 0.037 and P = 0.007, respectively). The fiber
      muffin top reduced postprandial serum insulin incremental area under the curve
      from 0 to 120 min by 38% compared with the control muffin top (P <0.001), which
      aligns with the blood glucose data. CONCLUSIONS: This study demonstrated that the
      inclusion of a practical dose of dietary fiber (11.6 g TDF) from VERSAFIBETM 2470
      RS in a bakery product significantly reduced postprandial glucose and insulin
      responses in healthy adults.

PMID- 29655780
TI  - Dietary flavonoid kaempferol inhibits glucocorticoid-induced bone loss by
      promoting osteoblast survival.
AB  - OBJECTIVE: Kaempferol, a dietary flavonoid found in fruits and vegetables, has
      been reported to reverse osteopenic condition in ovariectomized rats. Because
      kaempferol is endowed with osteogenic activity, the aim of this study was to
      determine whether it has a beneficial effect on glucocorticoid (GC)-induced bone
      loss. METHODS: Adult female rats were divided into four groups as control
      (vehicle; distilled water), methylprednisolone (MP; 5 mg*kg*d, subcutaneously),
      MP + kaempferol (5 mg*kg*d, oral), and MP + human parathyroid 1-34 (30 ug/kg, 5
      times/wk, subcutaneously) and treated for 4 wk. To study the antagonizing effect
      of kaempferol on GC-induced inhibition of fracture healing, drill-hole injury was
      performed on control and GC-treated rats. An oral dose of kaempferol was given
      for 14 d to observe the effect on callus formation at the site of injury. After
      treatment, bones were collected for further analysis. RESULTS: GC was associated
      with a decreased bone mineral density and impaired bone microarchitecture
      parameters. Consumption of kaempferol induced bone-sparing effects in GC-induced
      osteopenic condition. Additionally, improved callus formation at site of drill
      injury in femur diaphysis was observed with kaempferol consumption in animals on
      GC. Consistent with the in vivo data, kaempferol elicited a higher expression of
      osteogenic markers in vitro and antagonized the apoptotic effect of dexamethasone
      on calvarial osteoblasts. CONCLUSION: These results suggested that kaempferol
      reduced GC-induced bone loss and enhanced bone regeneration at fractured site,
      thus emphasizing the positive role of flavonoids on bone health.

PMID- 29655781
TI  - The hyperopic effect of narrow-band long-wavelength light in tree shrews
      increases non-linearly with duration.
AB  - During postnatal refractive development, an emmetropization mechanism uses
      refractive error to modulate the growth rate of the eye. Hyperopia (image focused
      behind the retina) produces what has been described as "GO" signaling that
      increases growth. Myopia (image focused in front of the retina) produces "STOP"
      signaling that slows growth. The interaction between GO and STOP conditions is
      non-linear; brief daily exposure to STOP counteracts long periods of GO. In young
      tree shrews, long-wavelength (red) light, presented 14 h per day, also appears to
      produce STOP signals. We asked if red light also shows temporal non-linearity;
      does brief exposure slow the normal decrease in hyperopia in infant animals? At
      11 days after eye opening (DVE), infant tree shrews (n = 5/group) began 13 days
      of daily treatment (red LEDs, 624 +/- 10 or 636 +/- 10 nm half peak intensity
      bandwidth) at durations of 0 h (normal animals, n = 7) or 1, 2, 4, or 7 h.
      Following each daily red period, colony lighting resumed. A 14 h red group had no
      colony lights. Refractive state was measured daily; ocular component dimensions
      at the end of the 13-day red-light period. Even 1 h of red light exposure
      produced some hyperopia. The average hyperopic shift from normal rose
      exponentially with duration (time constant 2.5 h). Vitreous chamber depth
      decreased non-linearly with duration (time constant, 3.3 h). After red treatment
      was discontinued, refractions in colony lighting recovered toward normal; the
      initial rate was linearly related to the amount of hyperopia. The red light may
      produce STOP signaling similar to myopic refractive error.

PMID- 29655782
TI  - Lithocholic acid, a bacterial metabolite reduces breast cancer cell proliferation
      and aggressiveness.
AB  - Our study aimed at finding a mechanistic relationship between the gut microbiome
      and breast cancer. Breast cancer cells are not in direct contact with these
      microbes, but disease could be influenced by bacterial metabolites including
      secondary bile acids that are exclusively synthesized by the microbiome and known
      to enter the human circulation. In murine and bench experiments, a secondary bile
      acid, lithocholic acid (LCA) in concentrations corresponding to its tissue
      reference concentrations (< 1 MUM), reduced cancer cell proliferation (by 10-20%)
      and VEGF production (by 37%), aggressiveness and metastatic potential of primary
      tumors through inducing mesenchymal-to-epithelial transition, increased antitumor
      immune response, OXPHOS and the TCA cycle. Part of these effects was due to
      activation of TGR5 by LCA. Early stage breast cancer patients, versus control
      women, had reduced serum LCA levels, reduced chenodeoxycholic acid to LCA ratio,
      and reduced abundance of the baiH (7alpha/beta-hydroxysteroid dehydroxylase, the
      key enzyme in LCA generation) gene in fecal DNA, all suggesting reduced microbial
      generation of LCA in early breast cancer.

PMID- 29655784
TI  - Aristolochic acid I interferes with the expression of BLCAP tumor suppressor gene
      in human cells.
AB  - Aristolochic acid I (AAI) is a phytocompound that is linked to the progressive
      renal disease and development of human urothelial carcinoma. The bladder cancer
      associated protein (BLCAP) gene exhibits a tumor suppressor function in various
      tumors, including bladder carcinoma. This study evaluated the effect of AAI on
      BLCAP expression and its associated mechanism in human cells. Administering AAI
      to human embryonic kidney cells (HEK293), human proximal tubule epithelial cells
      (HK-2) and urinary bladder cancer cells (HT-1376) significantly reduced the
      expression of BLCAP mRNA and protein. AAI also effectively suppressed the
      luciferase activities driven by BLCAP promoters of various lengths in HEK293
      cells. AAI significantly reduced both activator protein 1 (AP-1) and nuclear
      factor-kappaB (NF-kappaB) activities in reporter assays, but further point
      mutations revealed that Ap-1 and NF-kappaB binding sites on the BLCAP promoter
      were not AAI-responsive elements. Application of the DNA methyltransferase
      inhibitor, 5-aza-2'-deoxycytidine (5-aza-dC), reversed the decline of BLCAP
      expression that had been induced by AAI. However, AAI exposure did not alter
      hypermethylation of the BLCAP promoter, determined by methyl-specific polymerase
      chain reaction (PCR) and bisulfate sequencing. Knocking down BLCAP in HEK293 cell
      line enhanced the potential for cellular migration, invasion, and proliferation,
      along with the induction of a capacity for anchorage-independent growth. In
      conclusion, AAI down-regulated the expression of BLCAP gene and the deficiency in
      BLCAP expression contributed to the malignant transformation of human cells,
      implying that BLCAP may have a role in mediating AAI-associated carcinogenesis.

PMID- 29655783
TI  - Cytotoxicity of 34 FDA approved small-molecule kinase inhibitors in primary rat
      and human hepatocytes.
AB  - Of the 34 FDA approved oral small-molecule kinase inhibitors (KI), 23 (68%) have
      warnings for hepatotoxicity in product labeling. To better understand the
      mechanisms of KI hepatotoxicity and whether such effects can be predicted, we
      examined 34 KIs for cytotoxicity in primary rat and human hepatocytes. The
      hepatocytes were treated with KIs at ten concentrations normalized to maximal
      therapeutic blood levels (Cmax). At 5 and 24 h post treatment, lactate
      dehydrogenase or alanine aminotransferase leakage, caspase 3/7 activities and
      cellular adenosine triphosphate levels were measured. At 1 to 100-fold Cmax,
      while 5 KIs were neither toxic to human nor rat hepatocytes, 3 KIs showed similar
      cytotoxicity in both species and 26 KIs showed species-biased cytotoxicity, with
      16 KIs being more toxic to human hepatocytes and 10 KIs being more toxic to rat
      hepatocytes. At concentrations of 1-, 2.5-, 5-, 10-, 100-fold Cmax, the number of
      cytotoxic KIs in human hepatocytes was 4, 8, 11, 14 and 27, respectively, and the
      corresponding number in rat hepatocytes was 1, 4, 9, 12 and 27, respectively.
      When hepatocyte cytotoxicity at 100-fold Cmax was used to predict KI clinical
      hepatotoxicity reflected in product labeling, the accuracy was 0.65 with human
      hepatocytes and 0.59 with rat cells. When the criterion of daily dose >=100 mg or
      Cmax >=1.1 MUM was used to predict KI hepatotoxicity, the accuracy was 0.56 or
      0.47, respectively. These results suggest both indirect and direct drug-induced
      hepatocyte toxicity may contribute to the mechanisms of KI-induced hepatotoxicity
      seen clinically and use of primary hepatocytes is a useful in vitro model to help
      predict such toxicity.

PMID- 29655785
TI  - Characterization of 28S rRNA sequences of cestoda parasite Electrotaenia
      malapteruri Fritsch, 1886 from the Electric catfish Malapterurus electricus
      (Siluriformes: Malapteruridae).
AB  - Proteocephalids are cestoda parasites that mostly infect freshwater fish. The
      present study was carried out to investigate the presence of proteocephalids
      infecting the electric catfish Malapterurus electricus from Lake Manzala, Kafr El
      Sheikh Governorate, Egypt. Morphological characterization revealed the present
      parasite is a cestoda belonging to the genus Electrotaenia. Morphologically, the
      recovered worms were characterized by an elongated body measuring 100-127 (120 +/
      2) mm long and 0.92-2.11 (2.76 +/- 0.1) mm wide. The anterior part of the worm
      was obvious terminated at a spherical scolex measured 1.12-1.91 (1.72 +/- 0.01)
      mm long and 1.12-1.65 (1.42 +/- 0.01) mm wide with a rostellum-like apical organ
      equipped by 5-6 irregular rows of minute hooklets, as well as four uniloculate
      suckers with a diameter of 0.13-0.15 (0.14 +/- 0.01) mm and covered with
      microtriches. A long unsegmented neck was observed followed by acraspedote and
      anapolytic strobila consisted of 85-120 proglottids divided into 50-58 immature,
      12-19 mature, and up to 49 gravid proglottids. Molecular characterization based
      on 28S rRNA sequences was done to confirm the taxonomy of this parasite based on
      its morphology. It was observed that there was a close identity up to 72.0% with
      other protocephalid species obtained for comparison from the GenBank. Also, the
      data obtained revealed that there was high blast scores and low divergence
      between the present parasite and previously described Electrotaenia malapteruri
      (acc. no. JX477434). Phylogenetic analysis showed that the parasite sequence in
      conjunction with existing data investigates the placement of this protocephalid
      species within Proteocephalidea. It was shown that the present species is deeply
      embedded in the genus Electrotaenia with close relationships to other
      Electrotaenia malapteruri as a putative sister taxon.

PMID- 29655786
TI  - Quality Improvement Initiative to Prevent Admission Hypothermia in Very-Low-Birth
      Weight Newborns.
AB  - OBJECTIVE: To decrease rates of admission hypothermia (<36  degrees C) in very
      low-birth-weight (VLBW) newborns (<1,500 g). DESIGN: Quality improvement
      initiative. SETTING/LOCAL PROBLEM: Urban, Level IV NICU with 32 patient beds. The
      number of VLBW newborns admitted with temperatures less than 36  degrees C was
      greater than in comparable NICUs in the Vermont Oxford Network. PARTICIPANTS:
      Neonates born in 2016 who weighed less than 1,500 g at birth.
      INTERVENTION/MEASUREMENTS: Based on the literature and the needs of our unit, our
      team decided to focus efforts on equipment (chemical mattresses and polyurethane
      lined hats for newborns who weighed <1,000 g and polyurethane-lined hats for
      newborns who weighed <1,500 g), staff education/awareness, and temperature
      documentation and workflow. Axillary temperature measurements for all neonates
      who weighed less than 1,500 g were tracked on admission. RESULTS: The processes
      involved in this quality improvement initiative were successfully implemented,
      and use of new equipment began January 1, 2016. In 2016, only 9.6% (n = 7) of
      VLBW newborns were admitted with temperatures less than 36  degrees C, compared
      with 20.2% (n = 19) in 2015 and 32.4% (n = 24) in 2014 (p = .003). Overall, the
      mean admission temperature for neonates who weighed less than 1,500 g rose from
      36.2  degrees C in 2014 to 36.6  degrees C in 2016 (p = .001). CONCLUSION: We
      reduced the number of VLBW neonates admitted with temperatures less than 36 
      degrees C and increased overall admission temperatures for neonates who weighed
      less than 1,500 g with the addition of polyurethane-lined hats and chemical
      mattresses.

PMID- 29655787
TI  - Secretory expression and scale-up production of recombinant human thyroid
      peroxidase via baculovirus/insect cell system in a wave-type bioreactor.
AB  - The human thyroid peroxidase (hTPO) is an essential enzyme for thyroid hormone
      biosynthesis and is expressed in thyroid cells. It is an autoantigen against
      which antibodies are found in the sera of patients with a number of autoimmune
      thyroid disorders. Overexpression of hTPO has been achieved using the baculovirus
      expression vector system (BEVS). However, it is produced largely in an aggregated
      form in the cell lysate fraction, which increases the complexity of protein
      extraction. In this study, to achieve improved secretory expression of hTPO via
      BEVS, a truncated recombinant hTPO protein (hTPOt) was engineered by replacing
      its original signal peptide (SP) in the N-terminal with five heterologous SPs.
      Our data showed that the SP from the peptidyl-glycine alpha-amidating
      monooxygenase (PAM), referred to as SPPAM, significantly promoted the secretion
      of SPPAM-fused hTPOt (p-hTPOt) in High Five cells. Subsequently, we established
      an optimized scale-up production procedure for p-hTPOt in a 5-L wave-type
      bioreactor. The secretory p-hTPOt was purified by immobilized metal-chelating
      affinity chromatography and ion-exchange chromatography, achieving a protein
      purity of >95%. Finally, the purified p-hTPOt showed high sensitivity and
      specificity in reactions with positive or negative human serum samples via the
      double-antigen sandwich method, suggesting potential applications in hTPO-based
      research and product development.

PMID- 29655788
TI  - Antibody engineering to improve manufacturability.
AB  - Expression variation among antibodies produced by stably transfected Chinese
      Hamster Ovary (CHO) cells is well established. While developing CHO-K1 cell
      lines, we encountered a human monoclonal antibody, mAb B-c, with severe
      manufacturability issues, including very poor expression and high levels of heavy
      chain (HC) dimer and high molecular weight aggregates. Using transient expression
      in CHO-K1 cells, we identified light chain (LC) as the source of the
      manufacturability issues for this antibody. While other antibodies achieved
      optimal expression at 1:1 or 2:1 LC to HC ratios, mAb B-c required up to a 6:1
      LC:HC for maximal expression, which was still significantly lower than that for
      other tested antibodies. To overcome the manufacturability issues, LC shuffling
      was performed with the original HC to select antibodies with unique LCs which
      retained acceptable binding affinities. Transient CHO-K1 expression evaluation of
      the new LCs co-expressed with the original HC identified antibodies with high
      expression at a 1:1 or 2:1 LC:HC; the expression levels of these new antibodies
      were comparable to those of other well-expressed antibodies. Expression of these
      new antibodies in stably transfected CHO-K1 cells confirmed these results. In
      addition, antibodies containing the new LCs had very low levels of high molecular
      weight aggregates and HC dimer. These results demonstrate that certain antibody
      manufacturability issues can be attributed to LC and that engineering antibodies
      by pairing HCs with alternate LCs can improve antibody expression and product
      quality while maintaining or improving affinity.

PMID- 29655789
TI  - Interleukin-enhanced binding factor 2 interacts with NLRP3 to inhibit the NLRP3
      inflammasome activation.
AB  - The activation of the NLRP3 inflammasome is a key process of host immune response
      that establishes the first line of defense against pathogen infections and
      cellular stresses, whereas excessive inflammasome activation may damage the
      hosts, and thus it must be precisely controlled. However, the mechanism
      underlying the repression of the NLRP3 inflammasome activation remains largely
      unknown. In this study, by establishing and using a reconstructed NLRP3
      inflammasome activation system, we reveal that the NLRP3 inflammasome activation,
      pro-caspase-1 cleavage, and pro-interleukin-1beta (pro-IL-1beta) activation are
      repressed by the interleukin-enhanced binding factor 2 (ILF2). Further studies
      demonstrate that ILF2 represses the activation of NLRP3 inflammasome through
      interacting with the NACHT-associated domain (NAD) of NLRP3 and co-localized with
      NLRP3 in the cytoplasm of HEK293T cells. Finally, by generating a THP-1 cell line
      stably expressing ILF2 protein using the lentivirus infection system, we
      demonstrate that ILF2 represses ATP-induced activation of endogenous NLRP3
      inflammasome in macrophages. Therefore, this study identifies a new role of ILF2
      in the regulation of the NLRP3 inflammasome, and reveals a unique mechanism
      underlying the repression of the NLRP3 inflammasome activation.

PMID- 29655790
TI  - HDAC11 deletion reduces fructose-induced cardiac dyslipidemia, apoptosis and
      inflammation by attenuating oxidative stress injury.
AB  - Diabetes mellitus (DM) is a risk factor for abnormal heart development, but the
      molecular mechanism remains obscure. Histone deacetylase 11 (HDAC11), the most
      recently identified histone deacetylase, is the sole member of class IV HDACs.
      However, its role in diabetic cardiac injury is still poorly understood. In the
      present study, we attempted to explore the effects of HDAC11 on fructose (Fru)
      induced cardiac injury using the wild type (HDAC11+/+) and knockout (HDAC11-/-)
      mice. The results indicated that HDAC11 was significantly expressed in human and
      mouse diabetic heart failure (DHF) hearts. HDAC11-/- reduced the body weight,
      inguinal fat-pad mass, and elevated blood pressure in Fru-fed mice. Compared to
      HDAC11+/+/Fru group, cardiac function was significantly improved in HDAC11-/-/Fru
      mice. HDAC11-/-/Fru mice exhibited reduced cardiac triacylglycerol (TG), total
      cholesterol (TC) and free fatty acid (FFA) levels, along with decreased mRNA
      levels of lipid synthesis-, lipid storage- and lipid oxidation-associated genes.
      In addition, HDAC11-/- attenuated apoptosis, oxidative stress and inflammation in
      the heart of Fru-fed mice, as evidenced by the reduced cleavage of Caspase-3,
      nicotinamide adenine dinucleotide phosphate (NADPH), and xanthine oxidase (XOD)
      activity, enhanced superoxide dismutase (SOD) activity, as well as the decreased
      interleukin 1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) levels,
      which was accompanied with down-regulated p-NF-kappaB. The results above were
      verified in Fru-treated primary cardiomyocytes isolated from HDAC11+/+ or HDAC11
      /- mice. Intriguingly, suppressing the expressions of anti-oxidants using zinc
      protoporphyrin (ZnPP) or siNrf-2 siRNA markedly abolished the results that HDAC11
      suppression-induced reduction of apoptosis, reactive oxygen species (ROS)
      production, inflammation, as well as the improvement of dyslipidemia in Fru
      incubated primary cardiomyocytes. Thus, ROS production was responsible for HDAC11
      modulated diabetic heart injury. These findings suggested that suppressing HDAC11
      has therapeutic potential for treating diabetes mellitus-associated cardiac
      injury.

PMID- 29655791
TI  - Overexpression of a repressor MdMYB15L negatively regulates anthocyanin and cold
      tolerance in red-fleshed callus.
AB  - The cold-induced metabolic pathway and anthocyanin biosynthesis play important
      roles in plant growth. In this study, we identified a bHLH binding motif in the
      MdMYB15L protein using protein sequence analyses. Yeast two-hybrid and pull-down
      assays showed that MdMYB15L could interact with MdbHLH33. Overexpressing MdMYB15L
      in red-fleshed callus inhibited the expression of MdCBF2 and resulted in reduced
      cold tolerance but did not affect anthocyanin levels. Chip-PCR and EMSA analysis
      showed that MdMYB15L could bind the type II cis-acting element found in the
      MdCBF2 promoter. Overexpressing MdMYB15L in red-fleshed callus overexpressing
      MdbHLH33 also reduced cold tolerance and reduced MdbHLH33-induced anthocyanin
      biosynthesis. Knocking out the bHLH binding sequence of MdMYB15L (LBSMdMYB15L)
      prevented LBSMdMYB15L from interacting with MdbHLH33. Overexpressing LBSMdMYB15L
      in red-fleshed callus overexpressing MdbHLH33 also reduced cold tolerance and
      reduced MdbHLH33-induced anthocyanin biosynthesis. Together, these results
      suggested that an apple repressor MdMYB15L might play a key role in the cold
      signaling and anthocyanin metabolic pathways.

PMID- 29655792
TI  - Long non-coding RNA UCA1/miR-182/PFKFB2 axis modulates glioblastoma-associated
      stromal cells-mediated glycolysis and invasion of glioma cells.
AB  - Glioblastoma (GB) is the most common and deadliest malignant primary brain tumor
      with a high recurrence. In this study, lncRNA UCA1/miR-182 axis has been regarded
      as a nodal driver of glioma invasion mediated by GB-associated stromal cells
      (GASCs) and GASC-secreted chemokine CXCL14. In clinical specimens, CXCL14
      upregulation in GASCs also correlated with poor prognosis. Notably, CXCL14-high
      GASCs mediated lncRNA UCA1 upregulation and miR-182 downregulation in glioma
      cells. Moreover, miR-182 directly bound to the fructose-2,6-biphosphatase PFKFB2;
      UCA1/miR-182 axis thereby modulated GASC-induced glycolysis in glioma cells.
      Overall, UCA1/miR-182/PFKFB2 axis modulates chemokine CXCL14 secretion,
      glycolysis and invasion of glioma cells in GASCs.

PMID- 29655793
TI  - Inhibition of NLRP9b attenuates acute lung injury through suppressing
      inflammation, apoptosis and oxidative stress in murine and cell models.
AB  - Acute lung injury (ALI), known a severe disease along with high morbidity and
      mortality, is lacking of specific therapies. Inflammation, apoptosis and
      oxidative stress are critical pathologies that contribute to ALI. Recently, there
      is study indicated that NLRP9b, a NOD-like receptor (NLR) member, is critical in
      modulation of inflammatory response. However, the effects of NLRP9b on sepsis
      associated ALI, and the underlying molecular mechanism have not been understood.
      In the present study, the wild type (WT) and NLRP9b-knockout (NLRP9b-/-) mice
      with C57B/L6 background were subjected to a cecal ligation and puncture (CLP) for
      ALI murine model establishment. The findings indicated that NLRP9b-/- improved
      the survival rate of CLP-induced ALI mice, and inhibited pulmonary
      histopathological alterations, inflammation, and apoptosis. NLRP9b-/- reduced the
      activation of inhibitor of kappaBalpha/nuclear factor kappa B (IkappaBalpha/NF
      kappaB), apoptosis-associated speck-like protein containing a Caspase-recruitment
      domain (ASC)/Casapse-1 and Caspase-3/poly (ADP-ribose) polymerase (PARP)
      signaling pathways in CLP-challenged mice with ALI. In vitro, mouse epithelial
      cells (MLE-12) were incubated with lipopolysaccharide (LPS) or recombinant NLRP9b
      caused a significant increased of pro-inflammatory cytokines or chemokine, and
      reactive oxygen species (ROS) generation; however, these changes were markedly
      alleviated by NLRP9-knockdown using its specific siRNA sequence. Pre-treatment of
      MLE-12 cells with ROS scavenger of N-acetylcysteine (NAC) remarkably decreased
      lipopolysaccharide (LPS)- and rMuNLRP9-induced production of ROS, and the
      secretion of inflammatory cytokines or chemokine, as well as the activity of
      IkappaBalpha/NF-kappaB, ASC/Casapse-1 and Caspase-3/PARP signaling pathways.
      Together, the findings here suggested that NLRP9b played an essential role in
      lung inflammation, apoptosis and oxidative stress of sepsis-induced ALI animal
      model or in LPS-induced MLE-12 cells, providing that NLRP9b inhibition might be a
      potential therapeutic option for ALI.

PMID- 29655794
TI  - [Diagnosis in blood hypertension: When the techniques do not are accessible in
      primary care and are also produced inequities].

PMID- 29655795
TI  - Enhanced oral absorption of sorafenib via the layer-by-layer deposition of a pH
      sensitive polymer and glycol chitosan on the liposome.
AB  - This study aimed to design the effective formulation of sorafenib (SF) to enhance
      the oral drug absorption. Three liposomal formulations of SF were prepared
      including uncoated liposome (SF-Lip), glycol chitosan-coated liposome (GC-SF
      Lip), and Eudragit S100-glycol-chitosan coated liposome (SGC-SF-Lip). All
      formulations showed a narrow size distribution with a high encapsulation
      efficiency. Both GC-SF-Lip and SGC-SF-Lip exhibited good stability at acidic and
      neutral pHs without any significant drug leakage, while SF-Lip appeared to be
      unstable at pH 1.2. In the case of double coated SGC-SF-Lip, its size changed
      significantly at pH 7.4, due to the dissolution of Eudragit S100 coating layer
      into the surrounding medium. Compared to SF solution, all liposomal formulations
      demonstrated a higher cellular uptake in Caco-2 cells. In particular, SGC-SF-Lip
      displayed a lower cellular uptake than GC-SF-Lip at pH 6.5, but it achieved a
      similar cellular uptake to GC-SF-Lip at pH 7.4. Consistently, SGC-SF-Lip was less
      cytotoxic than GC-SF-Lip at pH 6.5, whereas it showed a comparable cytotoxicity
      to GC-SF-Lip at pH 7.4, implying the removal of the Eudragit S100 coating layer
      at pH 7.4. After an oral administration to rats, SGC-SF-Lip significantly
      improved the systemic exposure of SF, where its Cmax and AUC were approximately
      fourfold higher than the untreated drug. Collectively, SGC-SF-Lip appeared to be
      promising to enhance the oral absorption of SF.

PMID- 29655796
TI  - Broadband Acoustic Resonance Dissolution Spectroscopy (BARDS): A rapid test for
      enteric coating thickness and integrity of controlled release pellet
      formulations.
AB  - There are no rapid dissolution based tests for determining coating thickness,
      integrity and drug concentration in controlled release pellets either during
      production or post-production. The manufacture of pellets requires several
      coating steps depending on the formulation. The sub-coating and enteric coating
      steps typically take up to six hours each followed by additional drying steps.
      Post production regulatory dissolution testing also takes up to six hours to
      determine if the batch can be released for commercial sale. The thickness of the
      enteric coating is a key factor that determines the release rate of the drug in
      the gastro-intestinal tract. Also, the amount of drug per unit mass decreases
      with increasing thickness of the enteric coating. In this study, the coating
      process is tracked from start to finish on an hourly basis by taking samples of
      pellets during production and testing those using BARDS (Broadband Acoustic
      Resonance Dissolution Spectroscopy). BARDS offers a rapid approach to
      characterising enteric coatings with measurements based on reproducible changes
      in the compressibility of a solvent due to the evolution of air during
      dissolution. This is monitored acoustically via associated changes in the
      frequency of induced acoustic resonances. A steady state acoustic lag time is
      associated with the disintegration of the enteric coatings in basic solution.
      This lag time is pH dependent and is indicative of the rate at which the coating
      layer dissolves. BARDS represents a possible future surrogate test for
      conventional USP dissolution testing as its data correlates directly with the
      thickness of the enteric coating, its integrity and also with the drug loading as
      validated by HPLC.

PMID- 29655797
TI  - Pulmonary administration of a dry powder formulation of the antifibrotic drug
      tilorone reduces silica-induced lung fibrosis in mice.
AB  - The aim of this work was to study the antifibrotic effect of pulmonary
      administration of tilorone to lung fibrosis. L-leucine coated tilorone particles
      were prepared and their aerosolization properties were analyzed using two dry
      powder inhalers (Easyhaler and Twister). In addition, the biological activity and
      cell monolayer permeation was tested. The antifibrotic effect of tilorone
      delivered by oropharyngeal aspiration was studied in vivo using a silica-induced
      model of pulmonary fibrosis in mice in a preventive setting. When delivered from
      the Easyhaler in an inhalation simulator, the emitted dose and fine particle
      fraction were independent from the pressure applied and showed dose
      repeatability. However, with Twister the aerosolization was pressure-dependent
      indicating poor compatibility between the device and the formulation. The
      formulation showed more consistent permeation through a differentiated Calu-3
      cell monolayer compared to pristine tilorone. Tilorone decreased the histological
      fibrosis score in vivo in systemic and local administration, but only systemic
      administration decreased the mRNA expression of type I collagen. The difference
      was hypothesized to result from 40-fold higher drug concentration in tissue
      samples in the systemic administration group. These results show that tilorone
      can be formulated as inhalable dry powder and has potential as an oral and
      inhalable antifibrotic drug.

PMID- 29655798
TI  - A potential antibacterial wound dressing of cefadroxil chitosan nanoparticles in
      situ gel: Fabrication, in vitro optimization and in vivo evaluation.
AB  - Wound healing following skin injury is a natural phenomenon that usually lacks
      quality, rapidity, and aesthetics. Thus, the purpose of this study was to
      fabricate a new easily applied in situ gel of cefadroxil (CDX) loaded chitosan
      nanoparticles (CDX-CSNPs) that could promote wound healing, capable of inhibiting
      the possible accompanying bacterial infection. The nanoparticles were prepared by
      double emulsion technique and the influence of formulation parameters on drug
      entrapment efficiency (EE%), particle size (PS), polydispersity index (PDI) and
      zeta potential (ZP) were investigated using a full factorial design. The results
      show that the optimized CDX-CSNP1 composed of low molecular weight chitosan
      (0.2%w/v) was spherical with EE%, PS, PDI and ZP of 84.25 +/- 0.02, 408.30 +/-
      53.17 nm, 0.458 +/- 0.048 and 22.80 +/- 0.57 mV, respectively. DSC and XRD
      studies confirmed the amorphous nature of the drug. After ensuring the safety and
      non toxicity of CDX-CSNP1 in situ gel through cytotoxic study, the antibacterial
      activity was evaluated using a rat skin infection model against Staphylococcus
      aureus. Compared to the rats treated with free CDX, the CDX-CSNP1 treated group
      revealed a remarkable accelerated wound healing process and bacterial clearance
      which was further confirmed by the histopathological examination of skin
      biopsies.

PMID- 29655799
TI  - Stage-specific expression of the proline-alanine transporter in the human
      pathogen Leishmania.
AB  - Leishmania are obligatory intracellular parasites that cycle between the sand fly
      midgut (extracellular promastigotes) and mammalian macrophage phagolysosomes
      (intracellular amastigotes). They have developed mechanisms of adaptation to the
      distinct environments of host and vector that favor utilization of both proline
      and alanine. LdAAP24 is the L. donovani proline-alanine transporter. It is a
      member of Leishmania system A that translocates neutral amino acids. Since system
      A is promastigote-specific, we aimed to assess whether LdAAP24 is also expressed
      exclusively in promastigotes. Herein, we established that upon exposing L.
      donovani promastigotes to amastigote differentiation signal (pH 5.5 and 37 
      degrees C), parasites rapidly and completely degrade LdAAP24 protein in both
      axenic and in spleen-derived amastigotes. In contrast, LdAAP24 mRNA remained
      unchanged throughout differentiation. Addition of either MG132 or Bafilomycin A1
      partially inhibited LdAAP24 protein degradation, indicating a role for both
      lysosome- and proteasome-mediated degradation. This work provides the first
      evidence for post-translational regulation of stage-specific expression of
      LdAAP24.

PMID- 29655800
TI  - Effects of task complexity and age-differences on task-related functional
      connectivity of attentional networks.
AB  - Studies investigating the strength and membership of regions within multiple
      functional networks primarily focus on either resting state or single cognitive
      tasks. The goals of the current study were to investigate whether task-related
      functional connectivity changes with task complexity, and whether this
      connectivity-complexity relationship is age-sensitive. We assessed seed-to-voxel
      functional connectivity for the default mode network (DMN) and two attentional
      networks [cingulo-opercular (CO), fronto-parietal (FP)] in three cognitive
      control tasks of increasing complexity (Single task, Dual task, and Memory
      Updating), across younger and older adults (N = 52; NYoung = 23; NOld = 29). The
      three tasks systematically varied in cognitive control demands due to differing
      maintenance, switching, and updating requirements. Functional connectivity for
      all networks, resulting from task > rest contrasts, increased with greater task
      complexity, irrespective of age and gray matter volume. Moreover, between-network
      connectivity for DMN, CO, and FP regions was greatest for working memory
      updating, the most complex task. Regarding age-related differences in accuracy,
      none were observed for Single or Dual tasks, but older adults had poorer accuracy
      in Memory Updating. More anterior frontal clusters of functional connectivity
      were observed for older, compared to younger, adults; these were limited to seeds
      of the two attentional networks. Importantly, increased connectivity in these
      additional frontal regions in older adults were non-compensatory, because they
      were associated with detrimental task performance, especially Memory Updating.
      For the Memory Updating > Rest, the younger > older contrast resulted in greater
      DMN seed connectivity to regions in the other two attentional networks,
      implicating increased reliance on between-network connectivity for the DMN seeds
      during complex cognitive tasks. Our results also implicate functional
      connectivity between attentional networks and the cerebellum during cognitive
      control. Reliability of multiple seeds in the seed-to-voxel connectivity is also
      discussed.

PMID- 29655801
TI  - Analysis of intragenic USH2A copy number variation unveils broad spectrum of
      unique and recurrent variants.
AB  - Given that all forms of Usher syndrome (USH) present with hearing loss in advance
      of retinal disease, the syndromic nature of the disorder is rarely appreciated
      when critical management decisions are being made. As a result, molecular
      diagnostics are crucial in guiding the management of USH patients. While 11 genes
      have been associated with USH, the USH2A gene is one of the largest contributors.
      Approximately 20% of suspected USH probands that undergo USH2A sequencing at our
      laboratory receive an inconclusive result due to the identification of a
      monoallelic disease-causing variant in USH2A. Many studies suggest that
      intragenic deletions and duplications represent an important USH2A variant type
      that can be missed by sequencing assays if supplemental algorithms or testing
      methods are not applied. To gain a comprehensive view of the contribution of
      USH2A CNVs to USH, we conducted prospective and retrospective screening in 700
      hearing loss probands. Fourteen individuals with 11 unique USH2A CNVs are
      reported, including one pathogenic multi-exon duplication. Additionally, we
      mapped deletion breakpoints and performed a meta-analysis of USH2A CNVs to
      evaluate recurrence and underlying mechanisms. This analysis revealed breakpoint
      grouping within three introns, raising the possibility of CNV-susceptible regions
      within the gene. Overall, our data highlight the diversity of pathogenic CNVs in
      this gene, demonstrating that the comprehensive, high-resolution USH2A CNV
      analysis methods employed here are essential components of clinical genetic
      testing for USH.

PMID- 29655802
TI  - MARS variant associated with both recessive interstitial lung and liver disease
      and dominant Charcot-Marie-Tooth disease.
AB  - Aminoacyl-tRNA synthetases (ARSs) are ubiquitously expressed enzymes responsible
      for charging tRNA with cognate amino acids during protein translation. Non
      canonical functions are increasingly recognized, and include transcription and
      translation control and extracellular signaling. Monoallelic mutations in genes
      encoding several ARSs have been identified in axonal Charcot-Marie-Tooth (CMT2)
      disease, whereas biallelic mutations in ARS loci have been associated with multi
      tissue syndromes, variably involving the central nervous system, lung, and liver.
      We report a male infant of non-consanguineous origin, presenting with successive
      onset of transfusion-dependent anemia, hypothyroidism, cholestasis, interstitial
      lung disease, and developmental delay. Whole-exome sequencing (WES) revealed
      compound heterozygosity for two variants (p.Tyr307Cys and p.Arg618Cys) in MARS,
      encoding methionyl-tRNA synthetase. Biallelic MARS mutations are associated with
      interstitial lung and liver disease (ILLD). Interestingly, the p.Arg618Cys
      variant, inherited from an unaffected father, was previously reported in a family
      with autosomal dominant late-onset CMT2. Yeast complementation assays confirmed
      pathogenicity of p.Arg618Cys, yet suggested retained function of p.Tyr307Cys. Our
      findings underscore the phenotypic variability associated with ARS mutations, and
      suggest genetic or environmental modifying factors in the onset of monoallelic
      MARS-associated CMT2.

PMID- 29655804
TI  - Characterization of WDR20: A new regulator of the ERAD machinery.
AB  - ERAD is an important process of protein quality control that eliminates misfolded
      or unassembled proteins from ER. Before undergoing proteasome degradation, the
      misfolded proteins are dislocated from ER membrane into cytosol, which requires
      the AAA ATPase p97/VCP and its cofactor, the NPL4-UFD1 dimer. Here, we performed
      a CRISPR-based screen and identify many candidates for ERAD regulation. We
      further confirmed four proteins, FBOX2, TRIM6, UFL1 and WDR20, are novel
      regulators for ERAD. Then the molecular mechanism for WDR20 in ERAD is further
      characterized. Depletion of WDR20 inhibits the degradation of TCRalpha, a typical
      ERAD substrate, while WDR20 overexpression reduces TCRalpha protein level. WDR20
      associates with TCRalpha and central regulators of the ERAD system, p97, GP78 and
      HRD1. A portion of WDR20 localizes to the ER-containing microsomal membrane.
      WDR20 expression increases TCRalpha ubiquitination, and HRD1 E3 ligase is
      essential for the process. WDR20 seems to serve as an adaptor protein to mediate
      the interaction between p97 and TCRalpha. Our study provides novel candidates and
      reveals an unexpected role of WDR20 in ERAD regulation.

PMID- 29655805
TI  - Metabolic syndrome positively correlates with the risks of atherosclerosis and
      diabetes in a Chinese population.
AB  - BACKGROUND: Published studies seldom tested the weight of different waist
      circumference (WC) cut-off values for the diagnosis of metabolic syndrome (MetS)
      in predicting clinical outcomes, including cardiovascular disease and diabetes.
      METHODS: This is a Chinese population-based cross-sectional study screening
      subjects from a Health Examination Program since 1999 to 2015. The MetS
      identification and scores were determined either according to the Adult Treatment
      Panel III/American Heart Association/National Heart, Lung, and Blood Institute
      (ATP III/AHA/NHLBI)- or Asian-WC cut-off points. The developments of a higher
      brachial-ankle pulse wave velocity (baPWV), defined as >=1400 cm/s, and diabetic
      level hyperglycemia, defined as a high fasting glucose level >=6.99 mmol/L or
      postprandial glucose level ?11.10 mmol/L, were surveyed by comparing the areas
      under receiver operating characteristic curves (AUC-ROC) for both MetS scores.
      RESULTS: According to the ATP III/AHA/NHLBI- vs Asian-MetS criteria, 6633 vs 9133
      (24.8% vs 34.2%, p < 0.001) subjects were diagnosed as the MetS among 26,735
      study subjects with a mean age of 55 +/- 12 years. The stepwise increases in
      baPWV and prevalence of diabetic-level hyperglycemia were associated with both
      MetS scores after adjusting for age and sex. Both MetS scores yielded similar
      results for correlation with a higher baPWV (AUC-ROC = 0.685 for ATP III/AHA/HLBI
      vs 0.680 for Asian-MetS, p = 0.271) and diabetic-level hyperglycemia (AUC-ROC =
      0.791 for ATP III/AHA/HLBI- vs 0.784 for Asian-MetS, p = 0.546). CONCLUSIONS: In
      a stepwise manner, both ATP III/AHA/NHLBI- or Asian-MetS scores were strong risk
      factors for arterial stiffness and diabetes. Through a novel and holistic
      approach, the performance of the ATP III/AHA/NHLBI-MetS score for the risks of
      arterial stiffness and diabetes was comparable to the Asian-MetS score among a
      Chinese population.

PMID- 29655803
TI  - Role of MSC-derived galectin 3 in the AML microenvironment.
AB  - In acute myeloid leukemia (AML), high Galectin 3 (LGALS3) expression is
      associated with poor prognosis. The role of LGALS3 derived from mesenchymal
      stromal cells (MSC) in the AML microenvironment is unclear; however, we have
      recently found high LGALS3 expression in MSC derived from AML patients is
      associated with relapse. In this study, we used reverse phase protein analysis
      (RPPA) to correlate LGALS3 expression in AML MSC with 119 other proteins
      including variants of these proteins such as phosphorylated forms or cleaved
      forms to identify biologically relevant pathways. RPPA revealed that LGALS3
      protein was positively correlated with expression of thirteen proteins including
      MYC, phosphorylated beta-Catenin (p-CTNNB1), and AKT2 and negatively correlated
      with expression of six proteins including integrin beta 3 (ITGB3). String
      analysis revealed that proteins positively correlated with LGALS3 showed strong
      interconnectivity. Consistent with the RPPA results, LGALS3 suppression by shRNA
      in MSC resulted in decreased MYC and AKT expression while ITGB3 was induced. In
      co-culture, the ability of AML cell to adhere to MSC LGALS3 shRNA transductants
      was reduced compared to AML cell adhesion to MSC control shRNA transductants.
      Finally, use of novel specific LGALS3 inhibitor CBP.001 in co-culture of AML
      cells with MSC reduced viable leukemia cell populations with induced apoptosis
      and augmented the chemotherapeutic effect of AraC. In summary, the current study
      demonstrates that MSC-derived LGALS3 may be critical for important biological
      pathways for MSC homeostasis and for regulating AML cell localization and
      survival in the leukemia microenvironmental niche.

PMID- 29655806
TI  - Is there a role for intervention radiology for the treatment of lower limb deep
      vein thrombosis in the era of direct oral anticoagulants? A comprehensive review.
AB  - Despite recent advances in the treatment of Deep Vein Thrombosis (DVT) provided
      by Direct Oral Anticoagulants (DOAC), a substantial proportion of lower limb DVT
      patients will develop some degree of post-thrombotic syndrome (PTS) within 2
      years. Systemic thrombolysis, although effective in reducing the risk of PTS and
      leg ulceration, is associated with a high risk of major bleeding, making it
      unsuitable for the vast majority of patients. A local approach, aimed at
      delivering the fibrinolytic drug directly into, or near to, the thrombus surface,
      is attractive because of the possibility of lowering of the administered drug
      dose, thus reducing the bleeding risks. However, even after the recent
      publication of the ATTRACT trial, only weak evidence is available about the
      efficacy and safety of Catheter Directed Thrombolysis (CDT), either alone
      (pharmacological technique) or in combination with additional endovascular
      approaches (pharmacomechanical technique, PMT) including percutaneous mechanical
      thrombectomy, angioplasty with or without stenting and ultrasound-assisted CDT.
      The present review is aimed at providing the physicians with a comprehensive
      evaluation of the current evidence about this relevant topic, in order to build a
      reliable conceptual framework for a more appropriate use of this resource.

PMID- 29655807
TI  - Temporal trends of time in therapeutic range and incidence of cardiovascular
      events in patients with non-valvular atrial fibrillation.
AB  - BACKGROUND: Optimal time in therapeutic range (TTR) of vitamin K antagonists
      (VKAs) is crucial for cardiovascular events (CVEs) prevention in non-valvular
      atrial fibrillation (NVAF). The relationship between temporal changes of TTR and
      the incidence of CVEs has been poorly investigated. We investigated 1) temporal
      trends of TTR in a long-term follow-up of NVAF patients; 2) the incidence of CVEs
      according to changes of TTR. METHODS: Prospective observational study including
      1341 NVAF outpatients (mean age 73.5 years, 42.5% male) starting VKAs. Patients
      were divided into 4 groups: Group 0: Optimal TTR, consistently >=70% (n = 241);
      Group 1: Temporally worsening TTR, from above to below 70% (n = 263); Group 2:
      Temporally improving TTR, from below to above 70% (n = 270); Group 3: Suboptimal
      TTR, consistently <70% (n = 567). RESULTS: In a mean follow-up of 37.7 months
      (4214.2 patient-years), 108 CVEs occurred (2.6%/year). Survival analysis showed a
      graded increased risk of CVEs in relation to temporal changes in TTR, with the
      worst outcomes in Groups 1 and 3 (log-rank test p = 0.013). Multivariable Cox
      proportional hazards regression analysis showed that Group 1 vs. 0 (HR: 2.096;
      95%CI 1.061-4.139, p = 0.033), Group 3 vs. 0 (HR: 2.292; 95%CI 1.205-4.361, p =
      0.011), CHA2DS2VASc score (HR:1.316; 95%CI 1.153-1.501, p < 0.001) and PPIs
      (HR:0.453; 95%CI 0.285-0.721, p = 0.001) were independently associated with CVEs.
      CONCLUSION: A decrease of TTR <70% over time is observed in almost 20% of NVAF
      patients. Patients with worsening TTR temporally (ie. from initially above 70% to
      below 70%) have similar risk of CVEs of patients with consistently suboptimal
      anticoagulation.

PMID- 29655808
TI  - Impact of syncope and pre-syncope on short-term mortality in patients with acute
      pulmonary embolism.
AB  - BACKGROUND: Syncope and pre-syncope are well-known symptoms of acute pulmonary
      embolism (PE). However, data about their impact on short-term mortality are
      scant. We assess the short-term mortality (30-day) for all-causes in PE patients
      admitted with syncope or with pre-syncope, according their hemodynamic status at
      admission. METHODS: Patients from the prospective Italian Pulmonary Embolism
      Registry (IPER) were included in the study. At admission, subjects were
      stratified according to 2008 ESC guidelines (as high- and non-high-risk
      patients). RESULTS: Among the 1716 patients with confirmed acute PE, syncope or
      pre-syncope was the initial manifestation of the disease in 458 (26.6%) patients.
      Short-term mortality (30-day) for all causes were significantly higher in
      patients with syncope/presyncope (42.5% vs 6.2%, p < 0.0001) while PE patients
      with presyncope demonstrated a worst short-term outcome, in terms of mortality
      for all-causes, when compared to those subjects with syncope at admission (47.2%
      vs 37.4%, p = 0.03). A statistically significant difference in survival between
      pre-syncope and syncope was observed only in hemodynamically unstable patients
      [log rank p = 0.036]. Cox regression analysis confirmed that pre-syncope resulted
      an independent predictor of 30-day mortality in hemodynamically unstable patients
      at admission (HR 2.13, 95% CI 1.08-4.22, p = 0.029), independently from right
      ventricular dysfunction (RVD) (HR 6.23, 95% CI 3.05-12.71, p < 0.0001), age (HR
      1.03, 95% CI 1.00-1.06, p = 0.023) and thrombolysis (HR 2.27, 95% CI 1.11-4.66, p
      = 0.025). CONCLUSIONS: PE patients with syncope/presyncope had a higher 30-day
      mortality for all-causes as well as patients with presyncope had a worst short
      term outcome when compared to PE patients with syncope. Moreover, hemodynamically
      unstable patients with presyncope had a worst prognosis independently from the
      presence of RVD, age, positive cTn and thrombolytic treatment.

PMID- 29655809
TI  - Acute Limb Ischemia in an 8-Year-Old Patient: A Case Report.
AB  - We report the case of an 8-year-old patient with a history of nephrotic syndrome,
      who presented to the emergency department with right foot pain. The patient's
      mother described intermittent pain that woke her son from sleep and was
      accompanied by the foot turning purple and becoming cold to touch. Physical
      examination revealed capillary refill of over 10 seconds in the right and less
      than 2 seconds in the left foot. Ankle-brachial indices (ABIs) were 0.0 on the
      right and 0.96 on the left. The patient was admitted and started on therapeutic
      intravenous heparin. After consultation with his parents, right lower extremity
      angiography and thrombolysis was performed over 2 days. He subsequently underwent
      fasciotomy and amputation of the tip of all 5 toes. Eighteen months later, there
      is no leg length discrepancy, he is walking with foot inserts and has normal ABIs
      bilaterally.

PMID- 29655810
TI  - A Review of Interventions to Increase Vena Cava Filter Retrieval Rates.
AB  - BACKGROUND: Inferior vena cava filters (IVCFs) are indicated for therapeutic and
      prophylactic treatment of venous thromboembolism in patients when anticoagulation
      has failed or is contraindicated. Retrievable IVCFs are not always retrieved
      despite clinical recommendations. The purpose of this review is to compare
      results in the literature regarding interventions and to improve IVCF retrieval
      rates. METHODS: Articles were identified via the search terms "vena cava filters"
      and "inferior vena cava filters" in conjunction with "retrieval." Searches were
      repeated in MEDLINE/PubMed, Google Scholar, and Cochrane database. Exclusion
      criteria included duplicates, misidentified subject matter, study period before
      2008, and lack of control group. Two independent reviewers screened key elements
      in the identified manuscripts, including the targeted intervention population,
      study design, IVCF retrieval rates, and other outcomes. A third reviewer
      corroborated results and consolidated findings. RESULTS: Seventeen articles were
      identified for review. Of these, 12 were physician-targeted interventions, and 8
      were patient-targeted interventions (3 studies included both). IVCF retrieval
      rates varied substantially for each study, but all reviewed studies reported
      improvement in retrieval rate following intervention. Only 5 studies reported
      decreased IVCF indwell times in intervention groups. Reported complication rates
      from IVCF retrievals were low, ranging from 0 to 2%. CONCLUSIONS: IVCF retrieval
      rates were improved by all interventions in the reviewed studies. Findings
      suggest that IVCF retrieval rates can be best improved by tracking patients
      typically lost to follow-up. Literature suggests that successful tracking
      requires an individual or team of individuals who have been assigned dedicated
      clinical responsibility for coordinating care following IVCF placement.

PMID- 29655811
TI  - Retrograde Endovenous Laser Therapy Facilitates Great Saphenous Vein Closure in
      the Setting of Severe Vasospasm.
AB  - Antegrade access for endovenous laser therapy may be technically challenging due
      to patient body habitus, vasospasm, dehydration, and poor visibility of
      vasculature. This report describes a retrograde approach from the contralateral
      femoral vein to facilitate laser ablation of the great saphenous vein in the
      setting of vasospasm. Such a technique may provide a viable alternative in
      technically difficult situations.

PMID- 29655813
TI  - Synovial Chondromatosis in Patient Presenting with Chronic Venous Stasis Ulcers.
AB  - Synovial chondromatosis (SC) is a rare, benign synovial growth most frequently
      involving the knee or hip joint. Common presenting symptoms include pain
      throughout the affected joint, reduced range of motion, and a palpable mass. We
      present an unusual case of SC presenting with symptoms of chronic venous stasis
      ulcer. A 49-year-old patient presented with swelling, hyperpigmentation, and
      ulcerations of his right lower extremity. Work-up including duplex and computed
      tomography scan revealed a calcified mass in the hip joint, highly suspicious for
      SC. A joint surgical approach from a vascular and orthopedic surgeon successfully
      removed the growths and decompressed the surrounding vessels. The mass effect of
      the SC on overlying veins resulted in obstruction of venous return due and
      subsequent venous stasis ulcerations and symptoms of venous hypertension. We
      present this case due to the unique vascular sequelae related to the SC to
      explore this as a new diagnosis to consider in patients who present with venous
      stasis ulceration and radiographic findings consistent with SC.

PMID- 29655812
TI  - Routine Use of Ultrasound Guidance in Femoral Arterial Access for Peripheral
      Vascular Intervention Decreases Groin Hematoma Rates in High-Volume Surgeons.
AB  - BACKGROUND: There is a documented learning curve when adopting ultrasound
      guidance (UG) to aid vascular access. In the Vascular Study Group of New England
      (VSGNE), routine UG during percutaneous femoral artery access was shown to
      protect against the complication of groin hematoma. We sought to confirm this
      finding in the Vascular Quality Initiative (VQI), a data set with a larger sample
      size and broader geographic distribution, and to evaluate the effects of
      ultrasound usage and interventionalist volume on hematoma rates following
      peripheral vascular interventions (PVIs). METHODS: The VQI PVI database (2010
      2014) was queried to identify the complication of groin hematoma after 43,947
      PVIs performed via femoral artery access. Both procedure- and interventionalist
      level analyses were performed. Multivariable logistic regression was used to
      assess factors associated with hematoma. Multivariable Poisson regression
      analyses were used to compare hematoma rates between routine (>=80% of PVIs) and
      selective (<80% of PVIs) users of UG in the adjusted overall sample and in
      subgroups based on interventionalist volume (low: <10 PVIs/year; medium: 10-50
      PVIs/year; high: >50 PVIs/year). RESULTS: The overall groin hematoma rate was
      3.2%, and lower hematoma rates correlated with increasing annual
      interventionalist volume (low vs. medium vs. high volume: 3.7% vs. 3.4% vs. 2.9%;
      P = 0.011). UG was associated with increased risk of hematoma (odds ratio [OR]
      1.29, 95% confidence interval [CI] 1.13-1.47, P < 0.001), but this risk was
      isolated to patients treated by selective (OR 1.33, 95% CI 1.17-1.53, P < 0.001)
      rather than routine users of UG (OR 0.85, 95% CI 0.55-1.33, P = 0.484). In the
      overall interventionalist-level analysis, routine UG was not found to be
      protective against hematoma (rate ratio [RR] 0.97, 95% CI 0.85-1.11, P = 0.677),
      in contrast to what was previously reported from the VSGNE. However, subgroup
      analysis revealed that routine UG was further protective against hematoma among
      high-volume interventionalists (RR 0.73, 95% CI 0.54-0.97, P = 0.030).
      CONCLUSIONS: UG in percutaneous femoral artery access may decrease the
      complication rate of groin hematoma, especially as an interventionalist's volume
      increases and as selective use transforms into routine adoption. With repetition
      and practice, interventionalists likely overcome the learning curve associated
      with adoption of an unfamiliar technology and potentially improve patient
      outcomes.

PMID- 29655814
TI  - Safety and Efficacy of Arterial Closure Devices in an Office-Based Angiosuite.
AB  - INTRODUCTION: We aimed to compare the safety and efficacy of 5 arterial closure
      devices in an outpatient endovascular surgery center. METHODS: We retrospectively
      reviewed all cases using femoral arterial access performed between January 2012
      and December 2013. Five different arterial closure devices (AngioSeal, Perclose,
      StarClose, ExoSeal, and Mynx) were used by 7 endovascular surgeons. All femoral
      arteries were accessed with 6F sheaths under ultrasound guidance. All patients
      received systemic anticoagulation with sodium heparin (70 IU/kg). Sheath-shot
      angiograms of all arterial punctures were taken before deploying closure devices.
      Device failure was defined as any partial or complete failure requiring
      additional closure assistance. Minor complication was defined as any event that
      occurred because of incomplete hemostasis but did not result in hospitalization,
      including hematoma, hypotension, bleeding, arterial dissection, or extended
      recovery. Major complication was defined as any event that occurred because of
      incomplete hemostasis requiring inpatient management. Any device failure was
      identified per device and per surgeon. Device safety, efficacy, and relationships
      between other variables were analyzed using a binomial logistic regression.
      Results with P values < 0.05 were considered to be statistically significant.
      RESULTS: During the study period, there were a total of 3142 endovascular
      procedures, including 1976 arterial cases (62.9%). Out of 1898 femoral artery
      punctures, closure devices were used in 1810 (95.4%), which forms the basis of
      this report. Device failure occurred in 151 cases (8.34%), and minor
      complications occurred in 53 cases (2.93%). There were 11 hospitalizations
      (0.61%). AngioSeal had both the lowest device failure rate (3.5%) and minor
      complication rate (1.3%). Our data showed a significant difference between the
      respective arterial closure devices for device failure rate (P = 0.007) and minor
      complication rate (P = 0.049), but not for major complication rate (P = 0.199).
      No significant difference was observed between surgeons for device failure (P =
      0.798), minor complication (P = 0.218), or major complication rate (P = 0.899).
      CONCLUSIONS: With the lowest device failure and minor complication rate,
      AngioSeal is a consistently well-performing arterial closure device in the office
      surgical suite setting.

PMID- 29655815
TI  - Evidence for retinoic acid involvement in the regulation of vitellogenesis in the
      fresh water edible crab, Oziotelphusa senex senex.
AB  - The possible involvement of 13-cis retinoic acid (CRA) in the regulation of
      ovarian development in Oziotelphusa senex senex was investigated. Injection of
      CRA, into avitellogenic crabs significantly increased ovarian index, oocyte
      diameter and ovarian vitellogenin levels. Injection of CRA also resulted in a
      significant increase in the secretory rates of mandibular organs and Y-organs and
      circulatory levels of the methyl farnesoate and ecdysteroids. Further,
      administration of CRA into avitellogenic crabs produced higher amounts of
      Retinoid X Receptor, Ecdysteroid Receptor, E75 and vitellogenin mRNAs in the
      hepatopancreas. Mandibular organ and Y-organ explants isolated from avitellogenic
      crabs secreted more of methyl farnesoate and ecdysteroids respectively when
      incubated with CRA. Taken together, these observations led us to hypothesize that
      CRA stimulates ecdysteroidogenesis and methyl farnesoate synthesis, up-regulates
      EcR, RXR and E75 expression in hepatopancreas, which then induces vitellogenin
      gene expression. Vitellogenin is subsequently taken up from hemolymph by ovaries
      ensuing in ovarian maturation.

PMID- 29655817
TI  - The influence of insurance status on treatment and outcomes in oral cavity
      cancer: an analysis on 46,373 patients.
AB  - The purpose of this study was to determine the influence of insurance status on
      treatment and outcomes in oral cavity cancer. Patients were identified in the
      National Cancer Database (NCDB). Data were collected and analyzed using chi2
      tests, Kaplan-Meier methods, and multivariable Cox regression models. Those
      uninsured or on Medicaid were more likely to be younger (P<0.001), minority race
      (P<0.001), have a lower median household income (P<0.001), lower educational
      attainment (P<0.001), not undergo primary resection (P<0.001), present with
      higher T (P<0.001),N (P<0.001), and M (P<0.001) stage of disease, and have a
      higher tumor grade (P<0.001). On univariate analysis, those with private
      insurance had significantly better overall survival than those uninsured (hazard
      ratio (HR) 1.481), under Medicaid (HR 2.006), or on Medicare (HR 1.921). On
      multivariable Cox regression analysis, insurance status remained an independent
      prognosticator even after accounting for multiple demographic, socioeconomic,
      treatment, and clinicopathological factors. These data suggest that insurance
      status is associated with treatment and outcomes in patients with oral cavity
      cancer. Being uninsured or on Medicaid was found to be associated with a higher
      risk of a poorer prognosis when compared to private insurance, and the data
      suggest the need to expand comprehensive medical coverage and optimize access to
      adequate medical care in vulnerable patient populations.

PMID- 29655816
TI  - Sex-specific transcription and DNA methylation profiles of reproductive and
      epigenetic associated genes in the gonads and livers of breeding zebrafish.
AB  - Reproduction is an essential process for life and is regulated by complex hormone
      networks and environmental factors. To date, little is known about the
      contribution of epigenetic mechanisms to the regulation of reproduction,
      particularly in lower vertebrates. We used the zebrafish (Danio rerio) model to
      investigate the sex-specific transcription and DNA methylation profiles for genes
      involved in the regulation of reproduction and in epigenetic signalling in the
      livers and gonads. We found evidence for associations between DNA promotor
      methylation and transcription for esr1 (gonads and female livers), amh (gonads)
      and dnmt1 (livers). In the liver, esr1 was shown to be significantly over
      expressed in females compared to males, and its promoter was significantly hypo
      methylated in females compared to males. In the gonads, genes involved in
      epigenetic processes including dnmt1, dnmt3 and hdac1 were over-expressed in the
      ovary compared to the testis. In addition, dnmt1 and dnmt3 transcription in the
      testis was found to be strongly correlated with global DNA methylation. These
      data provide evidence of the sex-specific epigenetic regulation and transcription
      of genes involved in reproduction and epigenetic signalling in a commonly used
      vertebrate model.

PMID- 29655818
TI  - Risk factors and clinical outcomes of sinus membrane perforation during lateral
      window sinus lifting: analysis of 120 patients.
AB  - The aim of this study was to identify the risk factors associated with sinus
      membrane perforation and the effect of sinus membrane perforation and other risk
      factors on graft success and postoperative sinusitis. Sinus membrane perforation,
      graft failure, and postoperative sinusitis were tested for an association with
      age, sex, operator experience, side of the operation, residual bone height,
      presence of septa, presence of a mucous retention cyst, and smoking (chi2 test).
      Logistic regression analysis was used to model the odds ratio (OR) with
      corresponding risk factors. One hundred and twenty patients were included in this
      study. A total of 22 (18.3%) perforations occurred. A residual bone height of 3
      6mm (OR 6.808, P=0.002) and presence of septa (OR 4.023, P=0.025) were identified
      as significant risk factors. Twenty-eight (23.3%) sinus grafts were classified as
      failed. Membrane perforation (OR 16.819, P<0.005) and residual bone height of 3
      6mm (OR 5.363, P=0.01) were identified as significant risk factors for graft
      failure. None of the risk factors investigated in this study was significantly
      associated with postoperative sinusitis. These results suggest that the presence
      of septa and a residual bone height of 3-6mm are associated with an increased
      risk of sinus membrane perforation, and that sinus membrane perforation has a
      negative effect on graft success.

PMID- 29655819
TI  - In vitro study of a modified sagittal split osteotomy fixation technique of the
      mandible: a mechanical test.
AB  - This study was performed to evaluate the compressive mechanical strength of rigid
      internal fixation (RIF) using 1.5-mm L-shaped plates fixed with monocortical
      screws in sagittal split osteotomy (SSO). Thirty synthetic hemimandibles, which
      had all undergone a 5-mm advancement, were divided into three groups: three 12-mm
      bicortical titanium screws were placed in an inverted L pattern in group A; one
      straight 2.0-mm system spaced titanium plate fixed with four 5-mm monocortical
      screws was used in group B; two 1.5-mm system L-shaped titanium plates, each
      fixed with four 5-mm monocortical screws, were used in group C. The models were
      subjected to compressive and progressive mechanical tests with forces applied in
      the area between the second premolar and first molar to verify resistance in
      Newtons (N). A displacement speed of 1mm/min was applied, with a maximum 10mm
      displacement of the distal segment or until disruption of the fixation. The
      deformity and/or eventual rupture of the plates were evaluated, and consequently
      their technical stability was determined. The results showed that the modified
      fixation technique tested in this study on synthetic mandibles resulted in
      adequate stability and superior mechanical behaviour compared to simulated
      osteosynthesis with the use of a straight 2.0-mm titanium plate.

PMID- 29655821
TI  - Opening Opportunities With Open Data.

PMID- 29655820
TI  - Reprint of: Amorfrutin-type phytocannabinoids from Helichrysum umbraculigerum.

PMID- 29655822
TI  - Clinical Spectrum and Management of Heart Failure in Hypertrophic Cardiomyopathy.
AB  - Heart failure (HF), characterized by excessive exertional dyspnea, is a common
      complication within the broad clinical spectrum of hypertrophic cardiomyopathy
      (HCM). HF has become an increasingly prominent management issue with the
      reduction in sudden deaths due to use of implantable defibrillators in this
      disease. Exertional dyspnea ranges in severity from mild to severe (New York
      Heart Association functional classes II to IV) and not uncommonly becomes
      refractory to medical management, leading to progressive disability, but largely
      in the absence of pulmonary congestion and volume overload requiring
      hospitalization. HCM-related HF is most commonly due to dynamic mechanical
      impedance to left ventricular outflow produced by mitral valve systolic anterior
      motion, leading to high intracavity pressures. Surgical septal myectomy with low
      operative mortality (<1%) produces HF reversal and symptom relief in 90% to 95%
      of patients, while also conveying a survival benefit. Exercise echocardiography
      has assumed an important role in the evaluation of patients with HCM, i.e., by
      identifying candidates for septal reduction therapy with refractory HF when
      outflow gradients are present only with physiological exercise, distinguishing
      highly symptomatic nonobstructive patients as heart transplant candidates, and
      predicting future development of progressive HF. Notably, mortality directly
      attributable to HF has become exceedingly uncommon in HCM (<0.5%/year) in
      contrast with HF in non-HCM diseases (by 20-fold). In conclusion, HF in HCM is
      associated with diverse and complex pathophysiology, but a substantially more
      favorable prognosis than conventional non-HCM HF, and highly amenable to
      effective treatment options in the vast majority of patients.

PMID- 29655823
TI  - Heart Failure Costs, Minority Populations, and Outcomes: Targeting Health Status,
      Not Utilization, to Bend the Cost-Effectiveness Curve.

PMID- 29655824
TI  - Traveling the Interstices of Data Sharing.

PMID- 29655825
TI  - Hypertrophic Cardiomyopathy: Clinical Update.
AB  - Hypertrophic cardiomyopathy (HCM) is the most common heritable cardiomyopathy,
      manifesting as left ventricular hypertrophy in the absence of a secondary cause.
      The genetic underpinnings of HCM arise largely from mutations of sarcomeric
      proteins; however, the specific underlying mutation often remains undetermined.
      Patient presentation is phenotypically diverse, ranging from asymptomatic to
      heart failure or sudden cardiac death. Left ventricular hypertrophy and abnormal
      ventricular configuration result in dynamic left ventricular outflow obstruction
      in most patients. The goal of therapeutic interventions is largely to reduce
      dynamic obstruction, with treatment modalities spanning lifestyle modifications,
      pharmacotherapies, and septal reduction therapies. A small subset of patients
      with HCM will experience sudden cardiac death, and risk stratification remains a
      clinical challenge. This paper presents a clinical update for diagnosis, family
      screening, clinical imaging, risk stratification, and management of symptoms in
      patients with HCM.

PMID- 29655826
TI  - Exploiting the Natriuretic Peptide Pathway to Preserve Glomerular Filtration in
      Heart Failure.

PMID- 29655827
TI  - 30-Day Episode Payments and Heart Failure Outcomes Among Medicare Beneficiaries.
AB  - OBJECTIVES: The purpose of this study was to examine the association of 30-day
      payments for an episode of heart failure (HF) care at the hospital level with
      patient outcomes. BACKGROUND: There is increased focus among policymakers on
      improving value for HF care, given its rising prevalence and associated financial
      burden in the United States; however, little is known about the relationship
      between payments and mortality for a 30-day episode of HF care. METHODS: Using
      Medicare claims data for all fee-for-service beneficiaries hospitalized for HF
      between July 1, 2011, and June 30, 2014, we examined the association between 30
      day Medicare payments at the hospital level (beginning with a hospital admission
      for HF and across multiple settings following discharge) and patient 30-day
      mortality using mixed-effect logistic regression models. RESULTS: We included
      1,343,792 patients hospitalized for HF across 2,948 hospitals. Mean hospital
      level 30-day Medicare payments per beneficiary were $15,423 +/- $1,523. Overall
      observed mortality in the cohort was 11.3%. Higher hospital-level 30-day payments
      were associated with lower patient mortality after adjustment for patient
      characteristics (odds ratio per $1,000 increase in payments: 0.961; 95%
      confidence interval [CI]: 0.954 to 0.967). This relationship was slightly
      attenuated after accounting for hospital characteristics and HF volume, but
      remained significant (odds ratio per $1,000 increase: 0.968; 95% CI: 0.962 to
      0.975). Additional adjustment for potential mediating factors, including cardiac
      service capability and post-acute service use, did not significantly affect the
      relationship. CONCLUSIONS: Higher hospital-level 30-day episode payments were
      associated with lower patient mortality following a hospitalization for HF. This
      has implications for policies that incentivize reduction in payments without
      considering value. Further investigation is needed to understand the mechanisms
      that underlie this relationship.

PMID- 29655828
TI  - Venoarterial Extracorporeal Membrane Oxygenation in Cardiogenic Shock.
AB  - Venoarterial extracorporeal membrane oxygenation has emerged as a viable
      treatment for patients in cardiogenic shock with biventricular failure and
      pulmonary dysfunction. Advances in pump and oxygenator technology, cannulation
      strategies, patient selection and management, and durable mechanical circulatory
      support have contributed to expanded utilization of this technology. However,
      challenges remain that require investigation to improve outcomes.

PMID- 29655829
TI  - Renal Effects and Associated Outcomes During Angiotensin-Neprilysin Inhibition in
      Heart Failure.
AB  - OBJECTIVES: The purpose of this study was to evaluate the renal effects of
      sacubitril/valsartan in patients with heart failure and reduced ejection
      fraction. BACKGROUND: Renal function is frequently impaired in patients with
      heart failure with reduced ejection fraction and may deteriorate further after
      blockade of the renin-angiotensin system. METHODS: In the PARADIGM-HF
      (Prospective Comparison of ARNI with ACE inhibition to Determine Impact on Global
      Mortality and Morbidity in Heart Failure) trial, 8,399 patients with heart
      failure with reduced ejection fraction were randomized to treatment with
      sacubitril/valsartan or enalapril. The estimated glomerular filtration rate
      (eGFR) was available for all patients, and the urinary albumin/creatinine ratio
      (UACR) was available in 1872 patients, at screening, randomization, and at fixed
      time intervals during follow-up. We evaluated the effect of study treatment on
      change in eGFR and UACR, and on renal and cardiovascular outcomes, according to
      eGFR and UACR. RESULTS: At screening, the eGFR was 70 +/- 20 ml/min/1.73 m2 and
      2,745 patients (33%) had chronic kidney disease; the median UACR was 1.0 mg/mmol
      (interquartile range [IQR]: 0.4 to 3.2 mg/mmol) and 24% had an increased UACR.
      The decrease in eGFR during follow-up was less with sacubitril/valsartan compared
      with enalapril (-1.61 ml/min/1.73 m2/year; [95% confidence interval: -1.77 to 
      1.44 ml/min/1.73 m2/year] vs. -2.04 ml/min/1.73 m2/year [95% CI: -2.21 to -1.88
      ml/min/1.73 m2/year ]; p < 0.001) despite a greater increase in UACR with
      sacubitril/valsartan than with enalapril (1.20 mg/mmol [95% CI: 1.04 to 1.36
      mg/mmol] vs. 0.90 mg/mmol [95% CI: 0.77 to 1.03 mg/mmol]; p < 0.001). The effect
      of sacubitril/valsartan on cardiovascular death or heart failure hospitalization
      was not modified by eGFR, UACR (p interaction = 0.70 and 0.34, respectively), or
      by change in UACR (p interaction = 0.38). CONCLUSIONS: Compared with enalapril,
      sacubitril/valsartan led to a slower rate of decrease in the eGFR and improved
      cardiovascular outcomes, even in patients with chronic kidney disease, despite
      causing a modest increase in UACR.

PMID- 29655830
TI  - Medicare Expenditures by Race/Ethnicity After Hospitalization for Heart Failure
      With Preserved Ejection Fraction.
AB  - OBJECTIVES: The purpose of this study was to analyze cumulative Medicare
      expenditures at index admission and after discharge by race or ethnicity.
      BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a growing
      proportion of heart failure (HF) admissions. Research on health care expenditures
      for patients with HFpEF is limited. METHODS: Records of patients discharged from
      the Get With The Guidelines-Heart Failure registry between 2006 and 2014 were
      linked to Medicare data. The primary outcome was unadjusted payments for acute
      care services. Comparisons between race/ethnic groups were made using generalized
      linear mixed models. Cost ratios were reported by race/ethnicity, and adjustments
      were made sequentially for patient characteristics, hospital factors, and
      regional socioeconomic status. RESULTS: Median Medicare costs for index
      hospitalizations were $7,241 for the entire cohort, $7,049 for whites, $8,269 for
      blacks, $8,808 for Hispanics, $8,477 for Asians, and $8,963 for other races.
      Median costs at 30 days for readmitted patients were $9,803 and $17,456 for the
      entire cohort at 1-year. No significant differences were seen in index admission
      cost ratios by race/ethnicity. At 30 days among readmitted patients, costs were
      9% higher (95% confidence interval [CI]: 1% to 17%; p = 0.020) for blacks in the
      fully adjusted model than whites. At 1 year, costs were 14% higher (95% CI: 9% to
      18%; p < 0.001) for blacks, 7% higher (95% CI: 0% to 14%; p = 0.041) for
      Hispanics, and 24% higher (95% CI: 8% to 42%; p = 0.003) for patients of other
      races. No significant differences between white and Asian expenditures were
      noted. CONCLUSIONS: Minority patients with HFpEF have greater acute care service
      costs. Further research of improving care delivery is needed to reduce acute care
      use for vulnerable populations.

PMID- 29655831
TI  - Corrigendum to: "The NLRP3 inflammasome and the emerging role of colchicine to
      inhibit atherosclerosis-associated inflammation" [Atherosclerosis. 2018
      Feb;269:262-271].

PMID- 29655832
TI  - Serum magnesium, phosphorus, and calcium levels and subclinical calcific aortic
      valve disease: A population-based study.
AB  - BACKGROUND AND AIMS: Calcific aortic valve disease (CAVD) is the most common
      valve disease. Although micronutrients are known to contribute to cardiovascular
      disease, the relationship with CAVD remains poorly evaluated. We examined the
      association of serum levels of magnesium, phosphorus, and calcium with
      prevalence, incidence, and progression of aortic valve calcification (AVC).
      METHODS: We conducted a prospective study in a population-based sample of
      Japanese men aged 40-79 years without known cardiovascular disease and chronic
      kidney disease at baseline, and quantified AVC from serial computed tomographic
      images with the Agatston method. RESULTS: Of 938 participants at baseline (mean
      age, 63.7 +/- 9.9 years), AVC prevalence was observed in 173 (18.4%). Of 596
      participants without baseline AVC at follow-up (median duration, 5.1 years), AVC
      incidence was observed in 138 (23.2%). After adjustment for demographics,
      behaviors and cardiovascular risk factors, relative risks (95% confidence
      intervals) in the highest versus lowest categories of serum magnesium,
      phosphorus, and calcium were 0.62 (0.44-0.86), 1.45 (1.02-2.04), and 1.43 (0.95
      2.15), respectively, for AVC prevalence and 0.62 (0.42-0.92), 1.93 (1.28-2.91),
      and 1.09 (0.77-1.55), respectively, for AVC incidence. Their linear trends of
      serum magnesium and phosphorus were also all statistically significant. Of 131
      participants with baseline AVC, there was no association of any serum
      micronutrients with AVC progression. CONCLUSIONS: Serum magnesium was inversely
      associated, while serum phosphorus was positively associated with AVC prevalence
      and incidence, suggesting that these serum micronutrients may be potential
      candidates for risk prediction or prevention of CAVD, and warranting further
      studies.

PMID- 29655833
TI  - Development of Evidence-Based Surveillance Intervals After Radiofrequency
      Ablation of Barrett's Esophagus.
AB  - BACKGROUND & AIMS: Barrett's esophagus (BE) recurs in 25% or more of patients
      treated successfully with radiofrequency ablation (RFA), so surveillance
      endoscopy is recommended after complete eradication of intestinal metaplasia
      (CEIM). The frequency of surveillance is informed only by expert opinion. We
      aimed to model the incidence of neoplastic recurrence, validate the model in an
      independent cohort, and propose evidence-based surveillance intervals. METHODS:
      We collected data from the United States Radiofrequency Ablation Registry (US
      RFA, 2004-2013) and the United Kingdom National Halo Registry (UK NHR, 2007-2015)
      to build and validate models to predict the incidence of neoplasia recurrence
      after initially successful RFA. We developed 3 categories of risk and modeled
      intervals to yield 0.1% risk of recurrence with invasive adenocarcinoma. We fit
      Cox proportional hazards models assessing discrimination by C statistic and 95%
      confidence limits. RESULTS: The incidence of neoplastic recurrence was associated
      with most severe histologic grade before CEIM, age, endoscopic mucosal resection,
      sex, and baseline BE segment length. In multivariate analysis, a model based
      solely on most severe pre-CEIM histology predicted neoplastic recurrence with a C
      statistic of 0.892 (95% confidence limit, 0.863-0.921) in the US RFA registry.
      This model also performed well when we used data from the UK NHR. Our model
      divided patients into 3 risk groups based on baseline histologic grade: non
      dysplastic BE; indefinite for dysplasia, low-grade dysplasia, and high-grade
      dysplasia; or intramucosal adenocarcinoma. For patients with low-grade dysplasia,
      we propose surveillance endoscopy at 1 and 3 years after CEIM; for patients with
      high-grade dysplasia or intramucosal adenocarcinoma, we propose surveillance
      endoscopy at 0.25, 0.5, and 1 year after CEIM, then annually. CONCLUSION: In
      analyses of data from the US RFA and UK NHR for BE, a much-attenuated schedule of
      surveillance endoscopy would provide protection from invasive adenocarcinoma.
      Adherence to the recommended surveillance intervals could decrease the number of
      endoscopies performed yet identify unresectable cancers at rates less than 1/1000
      endoscopies.

PMID- 29655835
TI  - Risk of Serious and Opportunistic Infections Associated With Treatment of
      Inflammatory Bowel Diseases.
AB  - BACKGROUND & AIMS: The risk of infection associated with tumor necrosis factor
      antagonists (anti-TNF) and thiopurines (combination therapy) is uncertain. We
      assessed the risk of serious and opportunistic infections in patients with
      inflammatory bowel disease (IBD) treated with thiopurine monotherapy, anti-TNF
      monotherapy, or combination therapy in a large cohort of patients in France.
      METHODS: We performed a nationwide population-based study of patients (18 years
      or older) with a diagnosis of IBD in the French national health insurance
      database; we collected data from January 1, 2009 until December 31, 2014. The
      risks of serious and opportunistic infections associated with exposure to
      combination therapy, anti-TNF, and thiopurine monotherapies were compared using
      marginal structural Cox proportional hazard models adjusted for baseline and time
      varying sociodemographic characteristics, medications, and comorbidities.
      RESULTS: Among the 190,694 patients with IBD included in our analysis, 8561
      serious infections and 674 opportunistic infections occurred. Compared with anti
      TNF monotherapy, combination therapy was associated with increased risks of
      serious infection (hazard ratio [HR], 1.23; 95% confidence interval [CI], 1.05
      1.45) and opportunistic infection (HR, 1.96; 95% CI, 1.32-2.91). Compared with
      thiopurine monotherapy, anti-TNF monotherapy was associated with increased risks
      of serious infection (HR, 1.71; 95% CI, 1.56-1.88), mycobacterial infection (HR,
      1.98; 95% CI, 1.15-3.40), and bacterial infection (HR, 2.38; 95% CI, 1.23-4.58,
      respectively). Conversely, anti-TNF monotherapy was associated with decreased
      risk of opportunistic viral infection compared with thiopurine monotherapy (HR,
      0.57; 95% CI, 0.38-0.87). CONCLUSIONS: In a nationwide cohort study of patients
      with IBD in France, we found heterogeneity in risks of serious and opportunistic
      infections in patients treated with immune-suppressive regimens. These should be
      carefully considered and weighed against potential benefits for IBD treatment in
      patient management.

PMID- 29655834
TI  - Metformin Use Is Associated With Longer Progression-Free Survival of Patients
      With Diabetes and Pancreatic Neuroendocrine Tumors Receiving Everolimus and/or
      Somatostatin Analogues.
AB  - BACKGROUND & AIMS: Metformin seems to have anticancer effects. However, it is not
      clear whether use of glycemia and metformin affect outcomes of patients with
      advanced pancreatic neuroendocrine tumors (pNETs). We investigated the
      association between glycemia and progression-free survival (PFS) of patients with
      pNETs treated with everolimus and/or somatostatin analogues, as well as the
      association between metformin use and PFS time. METHODS: We performed a
      retrospective analysis of 445 patients with advanced pNET treated at 24 medical
      centers in Italy from 1999 through 2015. Data on levels of glycemia were
      collected at time of diagnosis of pNET, before treatment initiation, and during
      treatment with everolimus (with or without somatostatin analogues), octreotide,
      or lanreotide. Diabetes was defined as prior or current use of glycemia control
      medication and/or fasting plasma glucose level >= 126 mg/dL, hemoglobin A1c >=
      6.5% (48 mmol/L), or a random sample of plasma glucose >= 200 mg/dL (11.1
      mmol/L), with reported classic symptoms of hyperglycemia or hyperglycemic crisis.
      Patients were assigned to groups based on diagnosis of diabetes before or during
      antitumor therapy. PFS was compared between patients with vs without diabetes.
      Among patients with diabetes, the association between metformin use and PFS was
      assessed. We performed sensitivity and landmark analyses to exclude patients who
      developed diabetes while receiving cancer treatment and to exclude a potential
      immortal time bias related to metformin intake. RESULTS: PFS was significantly
      longer in patients with diabetes (median, 32.0 months) than without diabetes
      (median, 15.1 months) (hazard ratio for patients with vs without diabetes, 0.63;
      95% confidence interval, 0.50-0.80; P = .0002). PFS of patients treated with
      metformin was significantly longer (median PFS, 44.2 months) than for patients
      without diabetes (hazard ratio for survival of patients with diabetes receiving
      metformin vs without diabetes, 0.45; 95% confidence interval, 0.32-0.62; P <
      .00001) and longer than for patients with diabetes receiving other treatments
      (median PFS, 20.8 months; hazard ratio, 0.49; 95% confidence interval, 0.34-0.69;
      P < .0001). In multivariable analysis, adjusted for other factors associated with
      outcomes, metformin was associated with longer PFS but level of glycemia was not.
      Metformin was associated with increased PFS of patients receiving somatostatin
      analogues and in those receiving everolimus, with or without somatostatin
      analogues. Sensitivity and landmark analyses produced similar results.
      CONCLUSIONS: In a retrospective study of patients with pNETs, we found a
      significant association between metformin use and longer PFS.

PMID- 29655838
TI  - Exploring the effect of mesopore size reduction on the column performance of
      silica-based open tubular capillary columns.
AB  - We report on a modification in the hydrothermal treatment process of monolithic
      silica layers used in porous-layered open tubular (PLOT) columns. Lowering the
      temperature from the customary 95  degrees C to 80  degrees C, the size of the
      mesopores reduced by approximately about 35% from 12-13.5 nm to 7.5-9 nm, while
      the specific pore volume essentially remains unaltered. This led to an increase
      of the specific surface area (SA) of about 40%, quasi-independent of the porous
      layer thickness. The increased surface area provided a corresponding increase in
      retention, somewhat more (48%) than expected based on the increase in SA for the
      thin layer columns, and somewhat less than expected (34%) for the thick layer
      columns. The recipes were applied in 5 MUm i.d.-capillaries with a length of 60
      cm. Efficiencies under retained conditions amounted up to N = 137,000 for the
      PLOT column with a layer thickness (df) of 300 nm and to N = 109,000 for the PLOT
      column with df = 550 nm. Working under conditions of similar retention, the
      narrow pore/high SA columns produced with the new 80  degrees C recipe generated
      the same number of theoretical plates as the wide pore size/low SA columns
      produced with the 95  degrees C recipe. This shows the 80  degrees C-hydrothermal
      treatment process allows for an increase in the phase ratio of the PLOT columns
      without affecting their intrinsic mass transfer properties and separation
      kinetics. This is further corroborated by the fact that the plate height curves
      generated with the new and former recipe can both be well-fitted with the Golay
      Aris equation without having to change the intra-layer diffusion coefficient.

PMID- 29655837
TI  - Outcomes of Early Liver Transplantation for Patients With Severe Alcoholic
      Hepatitis.
AB  - BACKGROUND & AIMS: The American Consortium of Early Liver Transplantation for
      Alcoholic Hepatitis comprises 12 centers from 8 United Network for Organ Sharing
      regions studying early liver transplantation (LT) (without mandated period of
      sobriety) for patients with severe alcoholic hepatitis (AH). We analyzed the
      outcomes of these patients. METHODS: We performed a retrospective study of
      consecutive patients with a diagnosis of severe AH and no prior diagnosis of
      liver disease or episodes of AH, who underwent LT before 6 months of abstinence
      from 2006 through 2017 at 12 centers. We collected data on baseline
      characteristics, psychosocial profiles, level of alcohol consumption before LT,
      disease course and treatment, and outcomes of LT. The interval of alcohol
      abstinence was defined as the time between last drink and the date of LT. The
      primary outcomes were survival and alcohol use after LT, defined as slip or
      sustained. RESULTS: Among 147 patients with AH who received liver transplants,
      the median duration of abstinence before LT was 55 days; 54% received
      corticosteroids for AH and the patients had a median Lille score of 0.82 and a
      median Sodium Model for End-Stage Liver Disease score of 39. Cumulative patient
      survival percentages after LT were 94% at 1 year (95% confidence interval [CI],
      89%-97%) and 84% at 3 years (95% CI, 75%-90%). Following hospital discharge after
      LT, 72% were abstinent, 18% had slips, and 11% had sustained alcohol use. The
      cumulative incidence of any alcohol use was 25% at 1 year (95% CI, 18%-34%) and
      34% at 3 years (95% CI, 25%-44%) after LT. The cumulative incidence of sustained
      alcohol use was 10% at 1 year (95% CI, 6%-18%) and 17% at 3 years (95% CI, 10%
      27%) after LT. In multivariable analysis, only younger age was associated with
      alcohol following LT (P = .01). Sustained alcohol use after LT was associated
      with increased risk of death (hazard ratio, 4.59; P = .01). CONCLUSIONS: In a
      retrospective analysis of 147 patients who underwent early LT (before 6 months of
      abstinence) for severe AH, we found that most patients survive for 1 year (94%)
      and 3 years (84%), similar to patients receiving liver transplants for other
      indications. Sustained alcohol use after LT was infrequent but associated with
      increased mortality. Our findings support the selective use of LT as a treatment
      for severe AH. Prospective studies are needed to optimize selection criteria,
      management of patients after LT, and long-term outcomes.

PMID- 29655839
TI  - Free silanols and ionic liquids as their suppressors in liquid chromatography.
AB  - In this review, we will firstly discuss the types and the general properties of
      silica, focusing on the silica support used in chromatography and capillary
      electrophoresis. Additionally, the characterization of functional groups
      (silanols and siloxanes) will be considered in terms of activity of the
      stationary phases. We will then discuss physical chemistry of the stationary
      phases applied in liquid chromatography and capillary electrophoresis. The use of
      ionic liquids as a silanols' suppressors will be presented in the next parts of
      the study, along with the examples of specific applications. The review is
      completed with conclusions and an outlook for the future developments in the area
      of analytical applications of ionic liquids.

PMID- 29655836
TI  - Incidence of Hepatocellular Carcinoma in Patients With HCV-Associated Cirrhosis
      Treated With Direct-Acting Antiviral Agents.
AB  - BACKGROUND & AIMS: Studies have produced conflicting results of the incidence of
      hepatocellular carcinoma (HCC) in patients with hepatitis C virus-associated
      cirrhosis treated with direct-acting antivirals (DAAs). Data from clinics are
      needed to accurately assess the occurrence rate of HCC in patients with cirrhosis
      in the real world. METHODS: We collected data from a large prospective study of
      2,249 consecutive patients (mean age = 65.4 years, 56.9% male) with hepatitis C
      virus-associated cirrhosis (90.5% with Child-Pugh class A and 9.5% with Child
      Pugh class B) treated with DAAs from March 2015 through July 2016 at 22 academic
      and community liver centers in Sicily, Italy. HCC occurrence was evaluated by
      Kaplan-Meier curves. Cox regression analysis was used to identify variables
      associated with HCC development. RESULTS: A sustained virologic response (SVR)
      was achieved by 2,140 patients (total = 95.2%; 95.9% with Child Pugh class A and
      88.3% with Child Pugh class B; P < .001). Seventy-eight patients (3.5%) developed
      HCC during a mean follow-up of 14 months (range = 6-24 months). At 1 year after
      exposure to DAAs, HCC developed in 2.1% of patients with Child-Pugh class A with
      an SVR and 6.6% of patients with no SVR and in 7.8% of patients with Child-Pugh
      class B with an SVR and 12.4% of patients with no SVR (P < .001 by log-rank
      test). Albumin level below 3.5 g/dL (hazard ratio = 1.77, 95% confidence interval
      = 1.12-2.82, P = .015), platelet count below 120 * 109/L (hazard ratio = 3.89,
      95% confidence interval = 2.11-7.15, P < .001), and absence of an SVR (hazard
      ratio = 3.40, 95% confidence interval = 1.89-6.12, P < .001) were independently
      associated increased risk for HCC. The mean interval from exposure to DAAs to an
      HCC diagnosis was 9.8 months (range = 2-22 months) and did not differ
      significantly between patients with (n = 64, 9.2 months) and without (n = 14,
      12.0 months) an SVR (P = .11). A larger proportion of patients with an SVR had a
      single HCC lesion (78% vs 50% without an SVR; P = .009) or an HCC lesion smaller
      than 3 cm (58% vs 28% without an SVR; P = .07). CONCLUSIONS: In an analysis of
      data from a large prospective study of patients with hepatitis C virus-associated
      compensated or decompensated cirrhosis, we found that the SVR to DAA treatment
      decreased the incidence of HCC over a mean follow-up of 14 months.

PMID- 29655840
TI  - Capillary electrophoresis for aluminum ion speciation: Optimized separation
      conditions for complex polycation mixtures.
AB  - Aluminum chlorohydrates (ACH) are used in numerous applications and commercial
      products on a global scale including water treatment, catalysis or
      antiperspirants. They are complex mixtures of water soluble aluminum polycations
      of different degrees of polymerization, that are difficult to separate and
      quantify due to their susceptibility to depolymerize in solution when placed out
      of equilibrium, which is inherent to any separation process. We recently achieved
      the first capillary electrophoresis separation and characterization of ACH
      oligomers using 4-morpholineethanesulfonic acid (MES) as background electrolyte
      counter-ion. MES stabilizes the separated ACH oligomers during the
      electrophoretic process leading to highly repeatable and fast separations. In
      this work, the separation of ACH oligomers was further studied and perfected by
      varying the ionic strength, MES concentration and pH of the background
      electrolyte. Complex electrophoretic behavior is reported for the separation of
      Al13, Al30 and Na+ ions according to these experimental parameters. The
      transformation of the electropherograms in effective mobility scale and the use
      of the slope-plot approach are used to better understand the observed changes in
      selectivity/resolution. Optimal conditions (700 mM MES at 25 mM ionic strength
      containing 0.1 mM didodecyldimethylammonium bromide for dynamic capillary
      coating, pH 4.8) obtained for the separation of ACH oligomers are used for the
      baseline separation of samples difficult to analyze with other methods, including
      different molecular, aggregated and colloidal forms of aluminum from the Al13,
      Al30 and Na+ mixture, validating the rationale of the approach.

PMID- 29655841
TI  - Lysosomal acid lipase deficiency allograft recurrence and liver failure- clinical
      outcomes of 18 liver transplantation patients.
AB  - Lysosomal acid lipase deficiency (LAL-D) results in progressive microvesicular
      hepatosteatosis, fibrosis, cirrhosis, dyslipidemia, and vascular disease.
      Interventions available prior to enzyme replacement therapy development,
      including lipid lowering medications, splenectomy, hematopoietic stem cell and
      liver transplantation were unsuccessful at preventing multi-systemic disease
      progression, and were associated with significant morbidity and mortality. We
      report two sisters, diagnosed in infancy, who succumbed to LAL-D with accelerated
      disease progression following splenectomy and liver transplantation. The index
      patient died one year after hematopoietic stem cell transplant and liver
      transplantation. Her younger sister survived five years post liver
      transplantation, complicated by intermittent, acute rejection. Typical LAL-D
      hepatopathology, including progressive, microvesicular steatosis, foamy
      macrophage aggregates, vacuolated Kupffer cells, advanced fibrosis and
      micronodular cirrhosis recurred in the liver allograft. She died before a second
      liver transplant could occur for decompensated liver failure. Neither patient
      received sebelipase alfa enzyme replacement therapy, human, recombinant,
      lysosomal acid lipase enzyme, FDA approved in 2015. Here are reviewed 18 LAL-D
      post-liver transplantation cases described in the literature. Multi-systemic LAL
      D progression occurred in 11 patients (61%) and death in six (33%). These reports
      demonstrate that liver transplantation may be necessary for LAL-D-associated
      liver failure, but is not sufficient to prevent disease progression, or liver
      disease recurrence, since the pathophysiology is predominantly mediated by
      deficient enzyme activity in bone marrow-derived monocyte-macrophages. Enzyme
      replacement therapy addresses systemic disease and hepatopathology, potentially
      improving liver-transplantation outcomes. This is the first systematic review of
      liver transplantation for LAL-D, and the first account of liver allograft LAL-D
      associated hepatopathology recurrence.

PMID- 29655842
TI  - Infant Clinical Pain Assessment: Core Behavioral Cues.
AB  - : Diverse behavioral cues have been proposed to be useful cues in infant pain
      assessment, but there is a paucity of evidence on the basis of formal
      psychometric evaluation to establish their validity for this purpose. We aimed to
      examine 2 widely used coding systems, the Neonatal Facial Coding System (NFCS)
      and the Modified Behavior Pain Scale (MBPS), by examining their factor structures
      with confirmatory factor analysis using a large archival data set. The results
      indicated that an item-reduced NFCS scale with 3 items produced a 1-factor pain
      model that maintained the good psychometric properties of the 7-item scale. In
      addition, it was found that MBPS also has challenging internal consistency, with
      items that are weakly correlated as well as highly redundant. One item of the
      MBPS may be able to capture the construct of pain equally well or potentially
      improve its psychometric properties. Redefinition of the MBPS with cry as a sole
      indicator was suggested. This analysis provides 2 new iterations of the NFCS and
      MBPS that improve construct validity and internal consistency. These shorter
      versions also improve the feasibility of both measures and increase their
      potential for clinical use because less time is required for their
      administration. PERSPECTIVE: This article presents new iterations of the NFCS and
      MBPS scales. These revised measures improve the internal consistency of the
      measures, feasibility of use of the tools in research settings, and the
      efficiency of the coding process. The revised tools could also improve the
      feasibility of coding within clinical settings.

PMID- 29655843
TI  - Trait- and Frequency-Dependent Dysfunctional Habituation to Trigeminal
      Nociceptive Stimulation in Trigeminal Autonomic Cephalalgias.
AB  - : We investigated whether the stimulation frequency (SF), the pain phases, and
      different diagnoses of trigeminal autonomic cephalalgias (TACs) may influence the
      habituation to pain. We studied the habituation of the nociceptive blink reflex
      R2 responses at different SFs (.05, .1, .2, .3, .5, and 1 Hz), in 28 episodic
      cluster headache (ECH) patients, 16 during and 12 outside the bout; they were
      compared with 16 episodic paroxysmal hemicrania (EPH) during the bout and 21
      healthy subjects. We delivered 26 electrical stimuli and subdivided stimuli 2 to
      26 in 5 blocks of 5 responses for each SF. Habituation values for each SF were
      expressed as the percentages of the mean area value of second through fifth
      blocks with respect to the first one. A significant lower mean percentage
      decrease of the R2 area across all blocks was found at .2 to 1 Hz SF during ECH,
      outside of the ECH, and EPH compared with healthy subjects. We showed a common
      frequency-dependent deficit of habituation of trigeminal nociceptive responses at
      higher SFs in ECH and EPH patients, independently from the disease phase. This
      abnormal temporal pattern of pain processing may suggest a trait-dependent
      dysfunction of some underlying pain-related subcortical structures, rather than a
      state-dependent functional abnormality due to the recurrence of the headache
      attacks during the active period. PERSPECTIVE: TACs showed a frequency-related
      defective habituation of nociceptive trigeminal responses at the higher SFs,
      irrespectively of the diagnosis and/or the disease phase. We showed that the
      clinical similarities in the different subtypes of TACs are in parallel with a
      trait-dependent dysfunction in pain processing.

PMID- 29655844
TI  - On-line diagnosis of inter-turn short circuit fault for DC brushed motor.
AB  - Extensive research effort has been made in fault diagnosis of motors and related
      components such as winding and ball bearing. In this paper, a new concept of
      inter-turn short circuit fault for DC brushed motors is proposed to include the
      short circuit ratio and short circuit resistance. A first-principle model is
      derived for motors with inter-turn short circuit fault. A statistical model based
      on Hidden Markov Model is developed for fault diagnosis purpose. This new method
      not only allows detection of motor winding short circuit fault, it can also
      provide estimation of the fault severity, as indicated by estimation of the short
      circuit ratio and the short circuit resistance. The estimated fault severity can
      be used for making appropriate decisions in response to the fault condition. The
      feasibility of the proposed methodology is studied for inter-turn short circuit
      of DC brushed motors using simulation in MATLAB/Simulink environment. In
      addition, it is shown that the proposed methodology is reliable with the presence
      of small random noise in the system parameters and measurement.

PMID- 29655845
TI  - Cardiac telocytes. From basic science to cardiac diseases. I. Atrial
      fibrillation.
AB  - INTRODUCTION: Atrial fibrillation (AF) is nowadays considered to be one of the
      most important causes of heart failure, stroke, cognitive decline, vascular
      dementia, sudden death and overall cardiovascular morbidity. Recently were
      published a few articles suggesting a possible involvement of telocytes in the
      development of atrial fibrillation. The purpose of this article is to analyze the
      results obtained in the field systematically, and to see if there is enough data
      to support a possible involvement of telocytes in arrhythmogenesis. MATERIALS AND
      METHODS: To this end, we performed a systematic review of the relevant scientific
      literature, indexed in PubMed, Web of Science, and Scopus. RESULTS AND
      DISCUSSIONS: Our systematic review of the published data identified five articles
      containing original data, based on which the association between telocytes and
      atrial fibrillation was inferred in later studies. We analyzed the usefulness of
      the information contained in the original articles to support this association,
      showing a lack of definite proofs correlating telocytes with atrial fibrillation.
      CONCLUSIONS: Even if a few articles implied a potential association between AF
      and telocytes, the current data is not enough to support it. Moreover, even an
      association between the morphology, characteristics, or density of the telocytes
      in the atrium/pulmonary veins and AF is potentially speculative, and more studies
      should be performed before implying it with a reasonable degree of certainty.

PMID- 29655846
TI  - Telocyte-like cells containing Weibel-Palade bodies in rat lamina fusca.
AB  - Telocytes (TCs) are cells with long, thin and moniliform processes called
      telopodes. These cells have been found in numerous tissues, including the eye
      choroid and sclera. Lamina fusca (LF), an anatomical structure located at the
      sclera-choroid junction, has outer fibroblastic lamellae containing cells with
      long telopodes. The purpose of this study was to evaluate, via transmission
      electron microscopy, the LF for the presence of endothelial-specific
      ultrastructural features, such as Weibel-Palade bodies (WPBs), in the residing
      TCs. We found that the outer fibroblastic layer of LF lacked pigmented cells but
      contained numerous cells with telopodes. These cells had incomplete or absent
      basal laminae, were united by focal adhesions and close contacts, and displayed
      scarce caveolae and shedding vesicles. Within the stromal cells of LF, numerous
      WPBs in various stages of maturation and vesicular structures, as secretory pods
      that ensure the exocytosis of WPBs content, were observed. The WPBs content of
      the cells with telopodes in the LF could indicate either their involvement in
      vasculogenesis and/or lymphangiogenesis or that they are the P-selectin- and CD63
      containing pools that play roles in scleral or choroidal inflammation.

PMID- 29655847
TI  - Maternal air pollution exposure and preterm birth in Wuxi, China: Effect
      modification by maternal age.
AB  - BACKGROUND: Numerous studies have investigated prenatal air pollution and shown
      that air pollutants have adverse effect on birth outcomes. However, which
      trimester was the most sensitive and whether the effect was related to maternal
      age is still ambiguous. OBJECTIVES: This study aims to explore the association
      between maternal air pollution exposure during pregnancy and preterm birth, and
      if this relationship is modified by maternal age. METHODS: In this retrospective
      cohort study, we examine the causal relationship of prenatal exposure to air
      pollutants including particulate matters, which are less than 10 um (PM10), and
      ozone (O3), which is one of the gaseous pollutants, on preterm birth by
      gestational age. A total of 6693 pregnant women were recruited from Wuxi Maternal
      and Child Health Care Hospital. The participants were dichotomized into child
      bearing age group (< 35 years old) and advanced age group (> = 35 years old) in
      order to analyze the effect modification by maternal age. Logistic and linear
      regression models were performed to assess the risk for preterm birth
      (gestational age < 37 weeks) caused by prenatal air pollution exposure. RESULTS:
      With adjustment for covariates, the highest level of PM10 exposure significantly
      increased the risk of preterm birth by 1.42-fold (95% CI: 1.10, 1.85) compared
      those with the lowest level in the second trimester. Trimester-specific PM10
      exposure was positively associated with gestational age, whereas O3 exposure was
      associated with gestational age in the early pregnancy. When stratified by
      maternal age, PM10 exposure was significantly associated with an increased risk
      of preterm birth only in the advanced age group during pregnancy (OR:2.15, 95%
      CI: 1.13, 4.07). The results suggested that PM10 exposure associated with preterm
      birth was modified by advanced maternal age (OR interaction = 2.00, 95% CI: 1.02,
      3.91, Pinteraction = 0.032). CONCLUSION: Prenatal air pollution exposure would
      increase risk of preterm birth and reduced gestational age. Thus, more attention
      should be paid to the effects of ambient air pollution exposure on preterm birth
      especially in pregnant women with advanced maternal age.

PMID- 29655848
TI  - Impacts of exogenous pollutant bisphenol A on characteristics of soybeans.
AB  - Bisphenol A (BPA) is an endocrine disruptor that is ubiquitous in the
      environment. Previous studies have focused on the effects of BPA on plants to
      assess the ecological risk of BPA in the environment. To evaluate the effects of
      BPA on plant biological characters more systematically, we investigated the
      biological characters of above-ground and under-ground organs of soybean plants
      exposed to BPA. Meanwhile, the mechanisms for the observed changes were also
      analyzed from the view of hormone levels and photosynthesis. The results showed
      that after exposure to 0.8 mg L-1 BPA for three days, indole-3-acetic acid (IAA)
      and gibberellic acid levels in roots increased significantly, and the IAA level
      increased in leaves, so the character indices of roots and leaves both increased.
      The IAA and ethylene levels in stems increased, but the character indices of
      stems did not increased. With higher BPA concentrations, especially exposure to
      17.2 mg L-1 BPA, the levels of IAA, gibberellic acid, and zeatin decreased
      (except for the increased zeatin in leaves), and abscisic acid and ethylene
      levels increased; thus, all of the character indices significantly decreased. By
      comparing the changes in various biological characters, we found that leaf area,
      root surface area, and root length changed most significantly. In addition,
      changes in photosynthetic parameters provided initial causes for plant growth
      changes, and impacted biological characters. The changes of character indices
      were stronger when the BPA exposure time was prolonged, and after the removal of
      BPA, the character indices showed some recovery. Therefore, BPA exposure can
      regulate the changes in plant characters by influencing hormone levels and
      photosynthesis, and root surface area, root length, and leaf area were the most
      sensitive to BPA.

PMID- 29655849
TI  - Effect of cadmium on morphometric traits, antioxidant enzyme activity and
      phytochelatin synthase gene expression (SoPCS) of Saccharum officinarum var. cp48
      103 in vitro.
AB  - Cadmium is an important environmental pollutant which genetically,
      physiologically and biochemically affects the cell. Phytochelatins (PC) are
      involved in one of the phytoremediation mechanisms, in which they are able to
      bind heavy metals, such as cadmium. The objective of this study was to evaluate
      morphometric, antioxidant enzyme activity, and SoPCS gene expression in sugarcane
      growing under cadmium stress. After propagation, samples were cultured in
      triplicate for 14 days in modified MS medium containing CdCl2 (100, 250, 500
      umol). The morphometric traits, pigments, quantity and antioxidant enzyme
      activity were studied in treated plantlets. SoPCS gene expression was analyzed by
      qRT-PCR. Growth traits decreased following cadmium treatment. The amount of Chla,
      Chlb and ChlT decreased in treated samples, whereas carotenoids increased
      significantly. A rapid increase in antioxidant enzyme activity was detected.
      Enhanced SoPCS gene expression was observed in treated roots, whereas gene
      expression pattern in leaves was irregular. In conclusion, cadmium decreases the
      photosynthetic mechanism and growth rate in sugarcane. Antioxidative enzymes and
      SoPCS gene expression were significantly unregulated in sugarcane roots compared
      to the leaves. Cadmium concentration in shoots and roots of sugarcane
      significantly increased. The management of cadmium bioaccumulation in non-edible
      tissues of sugarcane such as leaves and roots that are sometimes burned after
      harvest can be applied for environmental protection.

PMID- 29655850
TI  - Biomonitoring role of some cellular markers during heat stress-induced changes in
      highly representative fresh water mollusc, Bellamya bengalensis: Implication in
      climate change and biological adaptation.
AB  - Owing to increasing concern of global climate-change, temperature rise is of
      great interest which can be primarily evaluated from the seasonal variations in
      some organisms. Aquatic environment can be extremely stressful to its inhabitants
      because most of them are poikilothermous. In the present study, attempt was made
      to evaluate the biological effects of oxidative-stress and adaptive/antioxidant
      capacities during temperature variations (36-40  degrees C for 24hrs to 72hrs) in
      Bellamya bengalensis both in environmental and laboratory conditions by testing
      some biomarkers like HSP70, catalase (CAT), superoxide dismutase (SOD), reduced
      glutathione (GSH) and glutathione reductase (GR). The biomarker potency of the
      molecules and the anti-oxidative metabolic-network was postulated and
      extrapolated to find its resemblance to the climate-change associated organismal
      variations. In a natural and eco-restored environment in the Eastern part of
      India, 10-20 fold increases in CAT, SOD and HSP70 protein expressions (Western
      blot results) were noticed in Bellamya paralleling to their increased enzymatic
      activities (gel zymogram studies) due to the seasonal (summer versus winter)
      temperature variation. It is evident from the consecutive three years' study that
      this variation resulted in the unfavorable physico-chemical changes of water
      quality parameters like dissolved oxygen, biochemical oxygen demand, alkalinity
      and consequently decreased the animal density in summer. And that was revived due
      to their higher reproduction-rate in post rainy/winter season when temperature
      normalizes resulting in a restoration of favorable environment. In laboratory
      condition, the reduced GR and increased GPx indicated the oxidative damage as
      evident by higher tissue MDA level following to higher mortality. Changes in SOD
      and CAT activities suggest activation of physiological mechanism to scavenge the
      ROS produced during heat stress. However, when mortality increased at different
      time points (36  degrees C - 72 h and 38  degrees C - 72 h), these enzyme
      activities also decreased as they failed to save the tissues from ROS. The
      results suggest that temperature variation does alter the active oxygen
      metabolism by modulating antioxidant enzyme activities, which can be used as
      biomarker to detect sub-lethal effects of climate change-associated pollution.
      The parity in environmental and laboratory experimental results may justify this
      laboratory experiment as model heat-stress experiment and indicate temperature as
      a universal stressor which alone or in combination with other water parameters
      initiates a consistent adapting behavior. The Bellamya bengalensis being the
      highest faunal representative in its habitat may serve as a good bioindicator
      species.

PMID- 29655851
TI  - Parvovirus B19 infection: An unusual aetiology of anaemia.

PMID- 29655852
TI  - Aidi injection plus platinum-based chemotherapy for stage IIIB/IV non-small cell
      lung cancer: A meta-analysis of 42 RCTs following the PRISMA guidelines.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Aidi injection is one of the most commonly used
      Chinese patent medicines for advanced non-small cell lung cancer (NSCLC). It is
      made from an extraction of Mylabris Phalerata, Radix Astragalus, Radix Ginseng,
      and Acanthopanax Senticosus. AIM OF THE STUDY: The objective of this study is to
      evaluate the efficacy and safety of Aidi injection in combination with platinum
      based chemotherapy for stage IIIB/IV NSCLC. MATERIALS AND METHODS: A systematic
      review and meta-analysis were performed following the PRISMA (the Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Trials were
      combined using Review Manager 5.3 and Comprehensive Meta-Analysis(CMA) 2.0.
      Dichotomous data were expressed as risk ratio (RR) and continuous outcomes as
      weighted mean difference (WMD), with their 95% confidence intervals (CI)
      respectively. All randomized controlled trials (RCTs) comparing Aidi injection
      plus platinum-based chemotherapy versus platinum-based chemotherapy, with
      efficacy and safety outcomes were selected. Disease Control Rate (DCR) was the
      primary outcome, Objective Response Rate (ORR), survival rate, quality of life
      (QOL), and toxic effects were the secondary outcomes. RESULTS: 42 RCTs recruiting
      4081 patients with stage IIIB/IV NSCLC were included, with overall low-moderate
      methodological quality. Compared with platinum-based chemotherapy alone, Aidi
      injection plus platinum-based chemotherapy can increase relative benefit of DCR
      (RR = 1.13, 95% CI 1.09-1.16, P < 0.00001), ORR (RR = 1.26, 95% CI 1.18-1.36, P <
      0.00001), improve 1-, 2-, 3-year survival rates (RR = 1.14, 95% CI 1.02-1.28, P =
      0.03; RR = 1.31, 95% CI 1.05-1.64, P = 0.02; and RR = 1.88, 95% CI 1.32-2.67, P =
      0.0005, respectively), QOL (RR = 1.80, 95% CI 1.61-2.01, P < 0.00001), and reduce
      severe (grade 3 and 4) toxicities by 36% (RR = 0.64, 95% CI 0.58-0.70, P <
      0.00001). CONCLUSIONS: From the available evidence, compared with platinum-based
      chemotherapy alone, Aidi injection plus platinum-based chemotherapy improves the
      clinical efficacy and alleviates the toxicity of chemotherapy in patients with
      stage IIIB/IV NSCLC. However, considering the intrinsic limitations of the
      included RCTs, well-designed, rigorously performed, high-quality trials are still
      required to further assess and confirm the results.

PMID- 29655853
TI  - Total saponins of Albiziae Cortex show anti-hepatoma carcinoma effects by
      inducing S phase arrest and mitochondrial apoptosis pathway activation.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Albiziae Cortex (AC) is a widely used traditional
      medicine in China. It is possess various properties to treat insomnia, traumatic
      injuries, diuresis, sthenia, and confusion. Total saponins of Albiziae Cortex
      (TSAC) are the most abundant bioactive components of AC, which were reported to
      show significant anti-tumor effects in vivo and in vitro. But the underlying
      mechanism of TSAC remained to be revealed. AIM OF STUDY: In this study, we
      investigated the anti-hepatoma carcinoma effects and the potential mechanism of
      TSAC in vivo and in vitro. MATERIALS AND METHODS: We first purified TSAC from
      crude extracts and characterized the major bioactive compounds by high
      performance liquid chromatography (HPLC). Effects of TSAC on viability of various
      hepatoma carcinoma cell lines were measured by MTT. Inhibition on cell
      proliferation was analysed using colony formation assay. Cell cycle distribution
      was revealed by flow cytometry. The apoptotic cells were observed by Hoechst
      33258 staining and acridine orange (AO)/ethidium bromide (EB) double staining.
      Microstructures of apoptotic cells were examined by Transmission electron
      microscopy (TEM). The mitochondrial membrane potential were determined by JC-1
      staining. Western blot was used to investigate the effects of TSAC on apoptosis
      related proteins, B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax),
      and S-phase related protein cyclin A, cyclin E and cyclin-dependent kinases 2
      (CDK2). Effects on tumor growth was assessed by H22-bearing ICR mice. RESULTS:
      TSAC significantly decreased the hepatoma carcinoma cell viability and inhibited
      HepG2 cell colony formation in a concentration-dependent manner. We also found
      that TSAC inhibited HepG2 cell growth via induction of S phase arrest. Further
      study showed that TSAC significantly down-regulated the expressions of cyclin A,
      cyclin E and CDK2 in HepG2 cells. Meanwhile, TSAC could effectively induce
      mitochondria-dependent caspase apoptosis pathway activation. Furthermore, TSAC
      increased the expression of pro-apoptotic protein Bax and decreased the
      expression of anti-apoptotic protein Bcl-2. In vivo assay showed that the anti
      tumor effects of TSAC were significantly augmented without increasing toxicity in
      H22-bearing ICR mice. CONCLUSION: TSAC could inhibit cell proliferation through
      inducing S phase arrest and activate cell apoptosis via mitochondria-dependent
      apoptosis pathway. Therefore, TSAC could be a promising agent in clinical trials
      for anti-hepatoma carcinoma treatment.

PMID- 29655854
TI  - The expression and distribution of a leptin receptor in the central nervous
      system, digestive organs, and gonads of the giant freshwater prawn, Macrobrachium
      rosenbergii.
AB  - In the present study, the presence and distribution of leptin receptor (LEP-R) in
      central nervous system, digestive organs, gonads of giant freshwater prawn,
      Macrobrachium rosenbergii, were investigated with Western blot and
      immunohistochemistry. By Western blot a LEP-R with a molecular weight (MW) of 100
      kDa was detected in the brain, thoracic ganglia, abdominal ganglia,
      hepatopancreas, all parts of the gastrointestinal tract, ovaries, and testes. In
      hepatopancreas and foregut, another intense positive band was detected at
      molecular weight of 30 kDa, which could be an isotype of LEP-R. By
      immunohistochemistry, LEP-R-ir was detected in the neurons, and neuropils in the
      brain, thoracic ganglia, and abdominal ganglia. In the gastrointestinal tract,
      there was intense LEP-R-ir in the apical part of the epithelial cells of the
      foregut, midgut, and hindgut. In addition, LEP-R-ir was found in the
      Restzellen(R)cells and Fibrillenzellen(F) cells in the hepatopancreas. In the
      ovary, LEP-R-ir was detected in early stage of oocytes and mature oocytes.
      Intense LEP-R-ir was observed in spermatogonia and spermatocytes of the small and
      orange claw male prawns. In addition, LEP-R was seen in the high epithelium of
      spermatic ducts from all male morphotypes. In summary, the detection of the LEP-R
      ir suggests the existence of a LEP-R in several organs of M. rosenbergii. Through
      binding with leptin peptide, LEP-R may be an important signaling molecule that
      has critical functions in modulating and controlling food intake, energy
      expenditure, and reproduction in this prawn.

PMID- 29655855
TI  - Corrigendum to "Targeting the gut-liver axis in liver disease" [J Hepatol 67
      (2017) 1084-1103].

PMID- 29655856
TI  - Acute and subchronic toxicities in dogs and genotoxicity of honokiol
      microemulsion.
AB  - This article aims to conduct toxicity test research on honokiol microemulsion(HM)
      to provide reference frame for the safe dose design as well as the toxic and
      adverse reaction monitoring in clinic. High performance liquid chromatography
      (HPLC) method was adopted to determine the concentration, stability and
      uniformity of HM and the results indicated that the test sample was conformed to
      the toxicity test requirements. In the acute toxicity test, six intravenous drip
      dosages, namely, 100.0, 66.7, 44.4, 19.8, 8.8, and 3.9 mg/kg were set, with one
      beagle dog in each dosage, respectively. In addition, the results also
      demonstrated that the approximate lethal dose range of HM was 66.7-100.0 mg/kg.
      In the subchronic toxicity test, beagle dogs were intravenously dripped with HM
      at doses of 1.25, 0.25 and 0.05 mg/kg for 30 days. During the test period, signs
      of gross toxicity, behavioral changes, body weight, rectal temperature, food
      consumption, ophthalmoscopy, electrocardiography, urinalysis, blood biochemistry,
      coagulation, hematology, organ weights and histopathology were examined. Under
      the present study conditions, the no-observed-adverse-effect level for HM was
      estimated to be 0.25 mg/kg. According to the results of bacterial reverse
      mutation, chromosomal aberration and micronucleus assays, HM exhibited no notable
      genotoxicity both in vivo and in vitro.

PMID- 29655857
TI  - The "sequence of prevention" for musculoskeletal injuries among adult
      recreational footballers: A systematic review of the scientific literature.
AB  - OBJECTIVE: To gather epidemiological information related to all steps of Van
      Mechelen's "sequence of prevention" for musculoskeletal injuries among adult
      recreational football players. METHODS: A systematic review of the scientific
      literature was conducted in Medline via Pubmed. Therefore, two highly sensitive
      search strategies based on three groups of keywords (and related search terms)
      were used. RESULTS: In total, 33 relevant original studies were included in our
      systematic review. The results of our systematic review showed that the incidence
      of musculoskeletal injuries among recreational adult football players ranged from
      9.6 to 15.8 injuries per 1000 exposure hours. These injuries are especially
      located in the ankle, knee, groin and hamstring, being associated with previous
      injury and match exposure. The FIFA11 + injury prevention programme and the
      Nordic Hamstring Exercise (NHE) were found to be effective for the reduction or
      prevention of musculoskeletal injuries among adult recreational football players.
      CONCLUSIONS: Our systematic review showed that musculoskeletal injuries are
      common among recreational adult football players, while effective preventive
      programmes are available. Further studies should focus on the identification and
      understanding of the key factors responsible for the optimal adoption,
      implementation and maintenance of these measures.

PMID- 29655858
TI  - Illuminating the Evolution of Iridescence.
AB  - Iridescence, a change in hue with viewing or illumination geometry, is a common
      feature of colour patterns in nature, though its significance remains elusive.
      Recent studies of floral iridescence reveal its functional versatility in
      enhancing the detection and discrimination of resources by insect viewers, as
      well as augmenting higher-level processes of memory and perception. Coupled with
      a known evolutionary lability, these results suggest intriguing possibilities for
      how this optical curiosity may act as a key to diversification.

PMID- 29655859
TI  - Rescuing cognitive and emotional regulatory skills to aid smoking prevention in
      at-risk youth: A randomized trial.
AB  - : Adolescence is a vulnerable period for smoking initiation, with disadvantaged
      teens particularly at risk. In addition, emotional and cognitive dysregulation is
      associated with an increased risk of smoking and makes it particularly
      challenging to benefit from standard substance use prevention interventions. The
      goal of the current study is to investigate the extent to which interventions
      designed to improve cognitive (working memory) and emotional (distress tolerance)
      regulatory processes enhance the effectiveness of a standard smoking prevention
      informational intervention. We will study adolescents (12-16 years of age)
      predominantly from racial/ethnic-minority and low-income households. Proximal
      smoking-risk outcome measures are used to allow testing of prevention models
      outside a full longitudinal study. We hope to generate new insights and
      approaches to smoking prevention among adolescents from lower socio-economic
      status (SES) by documenting the influence of working memory training and distress
      tolerance (mindfulness) interventions on cognitive/affective targets that place
      individuals at risk for smoking initiation and maintenance. CLINICAL TRIALS
      REGISTRATION: NCT03148652.

PMID- 29655860
TI  - Editorial comment regarding: Prospective multicenter study on robot-assisted
      laparoscopic extravesical ureteral reimplantation (RALUR-EV): Outcomes and
      complications.

PMID- 29655862
TI  - Influence of Percutaneous Endoscopic Gastrostomy on Gastroesophageal Reflux
      Disease in Children.
AB  - OBJECTIVE: To determine if gastroesophageal reflux disease (GERD) is present at
      long-term follow-up after percutaneous endoscopic gastrostomy (PEG), and to
      identify factors associated with the occurrence or aggravation of GERD after PEG
      placement. STUDY DESIGN: This prospective, observational study was conducted in
      our single tertiary center over a 13-year period (gastrostomy performed from 1990
      to 2003 and follow-up to 2015). Every child who underwent PEG in our center (N =
      368) from 1990 to 2003 was eligible. GERD was defined by clinical manifestations
      requiring antisecretory or prokinetic treatment, occurrence of a GERD-related
      complication, or the need for antireflux surgery. Outcomes among patients without
      antireflux surgery were also assessed. Multivariate analysis was used to identify
      factors aggravating GERD after PEG placement. RESULTS: A total 326 patients (89%;
      56% with a neurologic impairment) were studied with a median follow-up after 3.5
      years (range, 2.0-13.5 years). After PEG placement, GERD appeared in 11% of
      patients and was aggravated in 25% of patients with preexisting GERD. Factors
      associated with GERD worsening after PEG placement were neurologic impairment and
      preexisting GERD. Only 53 patients (16%) required antireflux surgery, among whom
      22 required surgery in the year after PEG. Neurologic impairment was the only
      factor significantly associated with the need for antireflux surgery.
      CONCLUSIONS: GERD predominantly remains clinically controlled after PEG
      placement. Routine antireflux surgery at the time of PEG placement is not
      justified.

PMID- 29655861
TI  - Age-related changes in urinary flow following dorsal inlay graft urethroplasty
      for hypospadias in early childhood: Potential improvement over 11 years of age.
AB  - INTRODUCTION: One of the goals of hypospadias repair is to create a neourethra
      with normal urinary stream and normal growth. Several studies have reported that
      dorsal inlay graft urethroplasty (DIG) has wide indications for various clinical
      phenotypes of hypospadias, with good short-term outcomes and few complications.
      However, there have been no reports that evaluated both short-term and long-term
      functional outcomes using uroflowmetry in patients with DIG. OBJECTIVE: The aim
      was to investigate whether uroflowmetry parameters change with time following DIG
      for hypospadias in early childhood. MATERIALS AND METHODS: Uroflowmetry
      parameters after DIG for hypospadias in childhood were retrospectively evaluated
      and compared between two defined ages at follow-up: 4-6 years and 11-13 years.
      Maximum urinary flow (Qmax) under the 25th percentile on the Miskolc nomogram was
      defined as obstruction. To evaluate the shapes of uroflow quantitatively, the
      flow index (FI) was used. The FI cut-offs for the flow shapes were defined as
      tower >1.253, plateaus <0.659; bells were between these two values. RESULTS:
      Thirty-four patients met the inclusion criteria. The median operative age was 1.8
      years (range 1.0-4.9 years). The median follow-up time was 10.3 years (range 7.2
      12.3 years). The mean +/- SD Qmax at the two follow-up times increased with time,
      from 9.2 +/- 3.7 to 18.8 +/- 7.8. The mean +/- SD FI changed from 0.53 +/- 0.19
      to 0.85 +/- 0.31. Both Qmax and the FI were significantly improved (p < 0.001, p
      < 0.001, respectively). There were significantly fewer patients with obstruction
      evaluated by the Miskolc nomogram at 11-13 years of age (n = 11, 32.4%) than at 4
      6 years (n = 31, 91.2%) (p < 0.001). Plateau shapes assessed by the FI were seen
      in 24 (70.6%) patients at 4-6 years and 10 (29.4%) patients at 11-13 years
      (Table). The number of patients with plateau shapes was significantly decreased
      (p = 0.001). DISCUSSION: Only one report noted long-term outcomes and spontaneous
      uroflowmetry resolution after tubularized incised plate urethroplasty. The
      current report is the first to present the short-term and long-term uroflowmetry
      outcomes after DIG. In addition, the FI was used for the first time to evaluate
      uroflowmetry after hypospadias repair. It was found that the uroflowmetry
      parameters improved spontaneously over 11 years of age following DIG for
      hypospadias in early childhood. CONCLUSION: Uroflowmetry parameters improved
      spontaneously over 11 years of age following DIG for hypospadias in early
      childhood.

PMID- 29655863
TI  - Applicability of the Curacao Criteria for the Diagnosis of Hereditary Hemorrhagic
      Telangiectasia in the Pediatric Population.
AB  - OBJECTIVE: To evaluate the accuracy of the clinical Curacao criteria in the
      diagnosis of hereditary hemorrhagic telangiectasia (HHT) in children and
      adolescents. STUDY DESIGN: This was a retrospective, multicenter chart review of
      673 patients evaluated between 2002 and 2016; 290 were eligible for the study.
      Genetic testing for a pathogenic mutation was considered the gold standard
      against which the clinical Curacao criteria were compared. Patients were divided
      into 4 age categories: 0-5, 6-10, 11-15, and 16-21-years. Sensitivity and
      specificity were calculated for each age group, and for the overall population.
      RESULTS: Overall the Curacao criteria had a sensitivity of 68% (95% CI 60%-76%)
      and a specificity of 98% (95% CI 91%-100%). Sensitivity was lowest in the 0- to 5
      year group, and increased with advancing age. The Curacao criteria had the
      highest sensitivity in the 16- to 21-year-olds. Specificity was 100% in all age
      groups except for the 11- to 15-year-olds. CONCLUSIONS: This study evaluated the
      use of the Curacao criteria for the diagnosis of HHT in the pediatric population
      with a family history of HHT. In those between the age of 0 and 21 years who meet
      1 criterion (unlikely HHT) or 2 criteria (possible HHT), genetic testing is
      preferred for diagnosis. The Curacao criteria appear to reliably diagnose HHT in
      children and adolescents who meet 3 or 4 criteria (definite HHT).

PMID- 29655864
TI  - Comparison of the Severity of Respiratory Disease in Children Testing Positive
      for Enterovirus D68 and Human Rhinovirus.
AB  - OBJECTIVE: To compare the characteristics and severity of respiratory disease in
      children testing positive for enterovirus D68 (EV-D68) and for human rhinovirus
      (RhV). STUDY DESIGN: A retrospective single center study of children presenting
      with acute respiratory symptoms and positive polymerase chain reaction for RhV/EV
      from September 1, 2014 through October 31, 2014 was performed. Specimens were
      subsequently tested specifically for EV-D68 and specimens identified as RhV were
      subtyped when possible into RhV-A, RhV-B, and RhV-C species. Clinical
      manifestations in patients with EV-D68 were compared with those with non-EV-D68,
      RhV, and RhV-C. RESULTS: Of the 173 patients included in the analysis, 72 tested
      positive for EV-D68, 61 for RhV, and 30 for RhV-C. There were significantly fewer
      infants in the EV-D68 group. Patients with EV-D68 were more likely than those
      without EV-D68, and specifically with RhV-C, to have fever and wheezing. Patients
      with EV-D68 received more magnesium sulfate for respiratory distress not
      responding adequately to repeated doses of inhaled albuterol. Hospitalized
      patients with EV-D68 received more bronchodilator therapy than patients with RhV.
      Patients with EV-D68 were more likely to be admitted to the intensive care unit
      and were older than patients without EV-D68. There was no difference in length of
      overall hospitalization or time in the pediatric intensive care unit.
      CONCLUSIONS: Children with EV-D68 appeared to have more severe respiratory
      disease on admission than children with RhV as evidenced by higher rates of
      fever, wheezing, bronchodilator use and pediatric intensive care unit admission.
      Despite the initial difference in severity, no significant difference in length
      of stay was found suggesting that patients with EV-D68 recovered as quickly as
      other groups.

PMID- 29655865
TI  - Non-Nutritive Sweeteners and Metabolic Health Outcomes in Children: A Systematic
      Review and Meta-Analysis.
AB  - OBJECTIVE: To systematically assess and quantitatively synthesize the literature
      regarding the association of consumption of non-nutritive sweeteners (NNS) during
      childhood with negative metabolic health outcomes. STUDY DESIGN: Following the
      PRISMA guidelines, published literature was systematically reviewed. Eligible
      studies (N = 13) were identified through the screening of over 2500 publications.
      Random-effects meta-analyses were conducted on the association of NNS consumption
      with body mass index (BMI) increase. Sensitivity and subgroup analyses by sex
      were also undertaken. RESULTS: Consumption of NNS during childhood and
      adolescence was associated with an increase in BMI (OR 1.15, 95% CI 1.06-1.25);
      the OR was similar in sensitivity analyses. The associations were positive but
      marginally significant in subanalyses by sex. The qualitative assessment of
      existing literature showed nonsignificant associations with other components of
      metabolic disease, such as waist circumference, fat mass accumulation, and type 2
      diabetes. CONCLUSIONS: Systematic assessment of observational studies showed no
      association of NNS intake during childhood with fat mass accumulation and waist
      circumference and a small, but statistically significant association with BMI
      increase. Inherent methodological weaknesses of to-date published investigations,
      including mainly underpowered size to explore the hypothesis, call for more
      research.

PMID- 29655866
TI  - Activation of GSK3beta/beta-TrCP axis via PHLPP1 exacerbates Nrf2 degradation
      leading to impairment in cell survival pathway during diabetic nephropathy.
AB  - NF-E2 p45-related factor 2 (Nrf2), is a major redox sensitive transcription
      factor that plays an essential role in regulating glucose metabolism.
      Inactivation of Nrf2 has been associated with diabetic complications however,
      mechanisms warranting Nrf2 suppression are incompletely understood. We
      hypothesized that PHLPP1 activates GSK3beta to induce beta-TrCP mediated Nrf2
      phosphorylation and degradation. In vivo study was carried out in STZ-NA induced
      type 2 diabetic male Wistar rats. GSK3beta mediated Nrf2 ubiquitination was
      confirmed by administration of GSK3beta inhibitor (LiCl; 60 mg/kg bwt.) which
      rapidly enhanced Nrf2 protein levels in STZ-NA treated diabetic rats. In
      addition, high glucose (30 mM; 48 h) treated renal proximal tubular cells NRK52E
      showed decreased Nrf2 nuclear localization, enhanced oxidative stress and
      caspase3 activation. While specific inhibition with GSK3beta inhibitor SB216763
      in vitro restored cellular homeostasis, glucose uptake and decreased apoptotic
      cell death. Immunoblotting and immunocytochemistry data demonstrated that
      aberrant renal glucose fluxes are associated with p53 mediated modulation in
      glucose transporter levels where expression of p53 is indirectly targeted through
      Nrf2 responsive MDM2 protein. Gene knockdown of PHLPP1 in NRK52E cells enhanced
      Nrf2-responsive antioxidant enzymes HO-1 and NQO-1 which suggested that PHLPP1 up
      regulation during hyperglycemia lowers Nrf2 stability via GSK3beta activation.
      More significantly, GSK3beta inhibition enhanced Nrf2-ARE binding compared to
      diabetic rats, providing further confirmation for GSK3beta/beta-TrCP pathway in
      suppressing Nrf2 activation during diabetic renal injury. Taken together, our
      results indicate that PHLPP1 up-surged Nrf2 nuclear instability by promoting
      Nrf2/beta-TrCP association and its inhibition may be critical in the management
      of diabetic nephropathy.

PMID- 29655867
TI  - Short-term sleep deprivation with exposure to nocturnal light alters
      mitochondrial bioenergetics in Drosophila.
AB  - Many studies have shown the effects of sleep deprivation in several aspects of
      health and disease. However, little is known about how mitochondrial
      bioenergetics function is affected under this condition. To clarify this, we
      developed a simple model of short-term sleep deprivation, in which fruit-flies
      were submitted to a nocturnal light condition and then mitochondrial parameters
      were assessed by high resolution respirometry (HRR). Exposure of flies to
      constant light was able to alter sleep patterns, causing locomotor deficits,
      increasing ROS production and lipid peroxidation, affecting mitochondrial
      activity, antioxidant defense enzymes and caspase activity. HRR analysis showed
      that sleep deprivation affected mitochondrial bioenergetics capacity, decreasing
      respiration at oxidative phosphorylation (OXPHOS) and electron transport system
      (ETS). In addition, the expression of genes involved in the response to oxidative
      stress and apoptosis were increased. Thus, our results suggest a connection
      between sleep deprivation and oxidative stress, pointing to mitochondria as a
      possible target of this relationship.

PMID- 29655868
TI  - A model of DNA unwinding dynamics by the RecBCD complex and its regulation by Chi
      recognition.
AB  - The Escherichia coli RecBCD enzyme is a heterotrimeric helicase-nuclease complex
      responsible for processing of double-stranded DNA breaks for repair by homologous
      recombination. It is a highly processive, duplex unwinding and degrading motor,
      with its activities being regulated by the octameric recombination hotspot, Chi,
      which is read as a single-stranded DNA sequence. Here, a model is presented for
      DNA unwinding by the RecBCD complex and its regulation by Chi recognition. With
      the model we study analytically the dynamics of DNA unwinding of both wild-type
      RecBCD and mutant RecBCDK177Q with the motor function of RecD being inactivated
      by mutagenesis, giving quantitative explanations of the available single-molecule
      experimental data. The peculiar features of RecBCD such as large variations of
      DNA unwinding speed of individual enzymes, sensitivity of unwinding speed of a
      RecBCD molecule on the change of environment, two translocase or helicase
      activities of RecBC and RecD, etc., are explained. Furthermore, predicted results
      are presented.

PMID- 29655869
TI  - A general structured model of a hermaphrodite population.
AB  - Both empirical and theoretical studies, have dealt with the question how to best
      optimize reproductive fitness for hermaphrodites, using models such as game
      theory or complicated energetic costs and benefits of mating displays. However,
      hermaphrodites exhibit a broad spectrum of sexual behaviors like simultaneous,
      sequential or lifetime gonochorist that cannot be explained using a unique
      formalism. A possible explanation of this diversity relies on the way these
      species maximize their fitness: Does the individual hermaphrodite split its time
      between strategies maximizing its instantaneous reproductive fitness or its
      evolutionary fitness? Here, we compare these two points of view and extend a game
      theoretical formalism to a sex allocation model that underlies all sexual
      behaviors as a result of a dynamic game whose payoff depends on the costs and
      benefits of sexual reproduction. Using this formalism, we prove that a
      simultaneous hermaphrodites strategy is stable even for high values of sex
      changing costs. Moreover, we prove that the stability of a sequential
      hermaphrodite is linked to the average energy allocated to the pure female
      strategy.

PMID- 29655870
TI  - Increased constitutive activation of NF-kappaB p65 (RelA) in peripheral blood
      cells of patients with progressive multiple sclerosis.
AB  - The NF-kappaB signalling pathway plays an important role in controlling cellular
      immune responses, inflammation and apoptosis. In multiple sclerosis (MS), there
      is evidence of dysregulation of NF-kappaB signalling in patients with a relapsing
      remitting disease course, but thus far there is little information on whether it
      is also dysregulated in patients with progressive disease. We hypothesised that
      patients with progressive MS would have more activation of NF-kappaB than
      relapsing-remitting MS patients. Using several different methods, we showed that
      there was more nuclear translocation of p65 in cells from progressive MS
      patients, particularly in T cells and monocytes. In addition, the amount of p65
      translocated to the nucleus in cells of patients with progressive MS was not
      increased upon non-specific activation of the cells with the mitogen Con A. These
      results suggest that NF-kappaB dysregulation occurs in patients with progressive
      MS patients, as well as those with relapsing-remitting MS.

PMID- 29655871
TI  - Cloning, partial sequencing and expression analysis of the neural form of P450
      aromatase (cyp19a1b) in the South America catfish Rhamdia quelen.
AB  - Brain aromatase is a key enzyme exclusively expressed in fish radial glial cells
      that convert androgens into estrogens, thus controlling neuroendocrine functions
      and neurogenesis. As an important step in characterizing the neuroendocrine
      systems of Rhamdia quelen (jundia), a partial cDNA sequence (1045 bp) of brain
      aromatase (cyp19a1b) was cloned and sequenced. At the nucleotide level the cDNA
      sequence was found to be 88% identical to cyp19a1b of two species of catfish,
      Ictalurus punctatus and Silurus meridionalis. The predicted amino acid sequence
      was between 80 and 91% similar to other teleosts. Real-time RT-qPCR analysis
      revealed that cyp19a1b was detected in pituitary, hypothalamus, telencephalon,
      head and posterior kidneys, liver and gonads (testis and ovary) of both males and
      females. The effects of E2 on cyp19a1b expression are sexually dimorphic in R.
      quelen. The injection of 17beta-estradiol (E2) decreased head kidney mRNA levels
      of cyp19a1b in males and increased cyp19a1b mRNA levels in the pituitary and head
      kidney of females. This study demonstrated that the R. quelen cyp19a1b gene is
      expressed in brain, pituitary and peripheral tissues in both males and females.

PMID- 29655872
TI  - [Contribution of the scrotal flap for the coverage of ischial and perineal
      pressure ulcers].
AB  - INTRODUCTION: The ischiatric pressure sore is a common pathology in rehabilitated
      spinal cord injured people, despite careful prevention. Medical treatment by
      discharge and directed healing is not always sufficient and surgery using local
      musculocutaneous flaps is often essential. Unfortunately, recidivism is frequent
      and the availability of local flaps is limited. The scrotal flap is an excellent
      complement to classic flaps, gluteal flaps or hamstrings. It can be used alone or
      in addition to another musculocutaneous flap, in first or second intention.
      MATERIAL AND METHODS: The scrotal flap is a musculocutaneous flap, using the
      Dartos, the platys muscle of the scrotum. It is richly vascularized, extensible
      and resistant. Its great plasticity makes it adaptable to any form of loss of
      substance, with an arc of rotation that can reach the anal margin. It can also be
      desepidermized and buried to fill a deep defect. Ten cases of scrotal flaps and
      their different indications are reviewed: some are used in first intention,
      others in addition to musculocutaneous flaps. RESULTS: The removal of a scrotal
      flap is fast and extremely easy. The simple closure of the donor site allows the
      sampling of half of the scrotum due to the great local laxity. The scrotal flaps
      achieved quickly healed, as well as the donor sites. Only one recurrence was
      observed after an inappropriate treatment of underlying osteitis. No
      complications have occurred. CONCLUSION: The scrotal musculocutaneous flap,
      reliable, resistant, quick and easy to remove is an excellent means of coverage
      of the perineal region. It can be used for the treatment of any loss of perineal
      substance in humans, but remains particularly useful for the treatment of ischial
      or perineal pressure sores.

PMID- 29655874
TI  - Differentiating clearly positive from indeterminate results: A review of
      irreproducible HIV-1 PCR positive samples from South Africa's Early Infant
      Diagnosis Program, 2010-2015.
AB  - We describe the extent of and variables associated with irreproducible HIV-1 PCR
      positive results within South Africa's Early Infant Diagnosis (EID) program from
      2010 to 2015 and propose criteria for differentiating indeterminate from clearly
      positive results using the COBAS(r) AmpliPrep/COBAS(r) TaqMan HIV-1 Qualitative
      Test version 2.0 (CAP/CTM Qual v2.0). Fourteen percent of specimens with an
      instrument-positive result that were repeat-tested yielded a negative result for
      which cycle threshold (Ct) proved to be the only predictive variable. A Ct <33.0
      was found to be the most accurate threshold value for differentiating clearly
      positive from irreproducible cases, correctly predicting 96.8% of results. Among
      70 patients with an irreproducible positive result linked to a follow up HIV-1
      PCR test, 67 (95.7%) were negative and 3 (4.3%) were instrument-positive.
      Criteria differentiating clearly positive from indeterminate results need to be
      retained within EID services and infants with indeterminate results closely
      monitored and final HIV status determined.

PMID- 29655873
TI  - Media portrayal of prenatal and postpartum marijuana use in an era of scientific
      uncertainty.
AB  - BACKGROUND: Objectives were to characterize how scientific information about
      prenatal and postpartum marijuana use was presented in online media content, and
      to assess how media portrayed risks and benefits of such marijuana use. METHODS:
      We analyzed online media items (n = 316) from March 2015 to January 2017. A
      codebook was developed to measure media content in 4 domains: scientific studies,
      information about health and well-being, mode of ingestion, and portrayal of
      risks and benefits. Content analysis was performed by two authors, with high
      inter-rater reliability (mean K = 0.82). Descriptive statistics were used to
      characterize content, and regression analyses were used to test for predictors of
      media portrayal of the risk-benefit ratio of prenatal and postpartum marijuana
      use. RESULTS: 51% of the media items mentioned health risks of prenatal and
      postpartum marijuana use. Nearly one-third (28%) mentioned marijuana use for
      treatment of nausea and vomiting in pregnancy. Most media items mentioned a
      specific research study. More than half of media (59%) portrayed prenatal or
      postpartum marijuana risks > benefits, 10% portrayed benefits> risks, and the
      remainder were neutral. While mention of a scientific study was not predictive of
      the portrayal of the risk-benefit ratio of marijuana use in pregnancy or
      postpartum, discussion of health risks and health benefits predicted portrayals
      of the risk-benefit ratio. CONCLUSIONS: Online media content about prenatal and
      postpartum marijuana use presented health risks consistent with evidence, and
      discussed a health benefit of marijuana use for nausea and vomiting in pregnancy.
      Portrayal of risks and benefits was somewhat equivocal, consistent with current
      scientific debate.

PMID- 29655875
TI  - Acetobacter oryzifermentans sp. nov., isolated from Korean traditional vinegar
      and reclassification of the type strains of Acetobacter pasteurianus subsp.
      ascendens (Henneberg 1898) and Acetobacter pasteurianus subsp. paradoxus (Frateur
      1950) as Acetobacter ascendens sp. nov., comb. nov.
AB  - Twelve Acetobacter pasteurianus-related strains with publicly available genomes
      in GenBank shared high 16S rRNA gene sequence similarity (>99.59%), but average
      nucleotide identity (ANI) and in silico DNA-DNA hybridization (DDH) values and
      multilocus sequence- and genome-based relatedness analyses suggested that they
      were divided into four different phylogenetic lineages. Relatedness analyses
      based on multilocus sequences, 1,194 core genes and whole-cell MALDI-TOF profiles
      supported that strains LMG 1590T and LMG 1591 (previously classified as the type
      strains of A. pasteurianus subsp. ascendens and paradoxus, respectively) and
      strain SLV-7T do not belong to A. pasteurianus. Strain SLV-7T, isolated from
      Korean traditional vinegar, shared low ANI (<91.0%) and in silico DDH (44.2%)
      values with all other Acetobacter type strains analyzed in this study, indicating
      that strain SLV-7T represents a new Acetobacter species. The phenotypic and
      chemotaxonomic analyses confirmed these results and therefore a new species named
      Acetobacter oryzifermentans sp. nov. is proposed with SLV-7T (=KACC 19301T=JCM
      31096T) as the type strain. Strains LMG 1590T and LMG 1591 shared high ANI
      (99.4%) and in silico DDH (96.0%) values between them, but shared low ANI
      (<92.3%) and in silico DDH (<49.0%) values with other type strains analyzed in
      this study, indicating that strains LMG 1590T and LMG 1591 should be reclassified
      into a new single species that should be named Acetobacter ascendens sp. nov.,
      comb. nov., with LMD 51.1T (=LMG 1590T=NCCB 51001T) as its type strain.

PMID- 29655876
TI  - Tolerance of uncertainty: A systematic review of health and healthcare-related
      outcomes.
AB  - BACKGROUND: Uncertainty tolerance (UT) is thought to be a characteristic of
      individuals that influences various outcomes related to health, healthcare, and
      healthcare education. We undertook a systematic literature review to evaluate the
      state of the evidence on UT and its relationship to these outcomes. METHODS: We
      conducted electronic and bibliographic searches to identify relevant studies
      examining associations between UT and health, healthcare, or healthcare education
      outcomes. We used standardized tools to assess methodological quality and
      analyzed the major findings of existing studies, which we organized and
      classified by theme. RESULTS: Searches yielded 542 potentially relevant articles,
      of which 67 met inclusion criteria. Existing studies were heterogeneous in focus,
      setting, and measurement approach, were largely cross-sectional in design, and
      overall methodological quality was low. UT was associated with various trainee
      centered, provider-centered, and patient-centered outcomes which were cognitive,
      emotional, and behavioral in nature. UT was most consistently associated with
      emotional well-being. CONCLUSIONS: Uncertainty tolerance is associated with
      several important trainee-, provider-, and patient-centered outcomes in
      healthcare and healthcare education. However, low methodological quality, study
      design limitations, and heterogeneity in the measurement of UT limit strong
      inferences about its effects, and addressing these problems is a critical need
      for future research.

PMID- 29655878
TI  - Fluid retention, aldosterone excess, and treatment of resistant hypertension.

PMID- 29655879
TI  - ST-Segment Elevation in Out-of-Hospital Cardiac Arrest Survivors Not Always
      Related to Obstructive Coronary Artery Disease.

PMID- 29655877
TI  - Endocrine and haemodynamic changes in resistant hypertension, and blood pressure
      responses to spironolactone or amiloride: the PATHWAY-2 mechanisms substudies.
AB  - BACKGROUND: In the PATHWAY-2 study of resistant hypertension, spironolactone
      reduced blood pressure substantially more than conventional antihypertensive
      drugs. We did three substudies to assess the mechanisms underlying this
      superiority and the pathogenesis of resistant hypertension. METHODS: PATHWAY-2
      was a randomised, double-blind crossover trial done at 14 UK primary and
      secondary care sites in 314 patients with resistant hypertension. Patients were
      given 12 weeks of once daily treatment with each of placebo, spironolactone 25-50
      mg, bisoprolol 5-10 mg, and doxazosin 4-8 mg and the change in home systolic
      blood pressure was assessed as the primary outcome. In our three substudies, we
      assessed plasma aldosterone, renin, and aldosterone-to-renin ratio (ARR) as
      predictors of home systolic blood pressure, and estimated prevalence of primary
      aldosteronism (substudy 1); assessed the effects of each drug in terms of
      thoracic fluid index, cardiac index, stroke index, and systemic vascular
      resistance at seven sites with haemodynamic monitoring facilities (substudy 2);
      and assessed the effect of amiloride 10-20 mg once daily on clinic systolic blood
      pressure during an optional 6-12 week open-label runout phase (substudy 3). The
      PATHWAY-2 trial is registered with EudraCT, number 2008-007149-30, and
      ClinicalTrials.gov, number NCT02369081. FINDINGS: Of the 314 patients in PATHWAY
      2, 269 participated in one or more of the three substudies: 126 in substudy 1,
      226 in substudy 2, and 146 in substudy 3. Home systolic blood pressure reduction
      by spironolactone was predicted by ARR (r2=0.13, p<0.0001) and plasma renin
      (r2=0.11, p=0.00024). 42 patients had low renin concentrations (predefined as the
      lowest tertile of plasma renin), of which 31 had a plasma aldosterone
      concentration greater than the mean value for all 126 patients (250 pmol/L).
      Thus, 31 (25% [95% CI 17-33]) of 126 patients were deemed to have inappropriately
      high aldosterone concentrations. Thoracic fluid content was reduced by 6.8% from
      baseline (95% CI 4.0 to 8.8; p<0.0001) with spironolactone, but not other
      treatments. Amiloride (10 mg once daily) reduced clinic systolic blood pressure
      by 20.4 mm Hg (95% CI 18.3-22.5), compared with a reduction of 18.3 mm Hg (16.2
      20.5) with spironolactone (25 mg once daily). No serious adverse events were
      recorded, and adverse symptoms were not systematically recorded after the end of
      the double-blind treatment. Mean plasma potassium concentrations increased from
      4.02 mmol/L (95% CI 3.95-4.08) on placebo to 4.50 (4.44-4.57) on amiloride
      (p<0.0001). INTERPRETATION: Our results suggest that resistant hypertension is
      commonly a salt-retaining state, most likely due to inappropriate aldosterone
      secretion. Mineralocorticoid receptor blockade by spironolactone overcomes the
      salt retention and resistance of hypertension to treatment. Amiloride seems to be
      as effective an antihypertensive as spironolactone, offering a substitute
      treatment for resistant hypertension. FUNDING: British Heart Foundation and UK
      National Institute for Health Research.

PMID- 29655880
TI  - Efficacy and Safety of the HeartMate Percutaneous Heart Pump During High-Risk
      Percutaneous Coronary Intervention (from the SHIELD I Trial).
AB  - This study aimed to evaluate the use of the HeartMate percutaneous heart pump, a
      catheter-based axial flow pump designed to provide partial left ventricular
      support, in patients who underwent high-risk percutaneous coronary intervention
      (PCI). Patients who are hemodynamically unstable, or at risk of being
      hemodynamically unstable, while undergoing PCI may require mechanical circulatory
      support. Fifty high-risk patients were enrolled in a prospective, nonrandomized,
      multicenter, open-label trial. Primary end points were freedom from hemodynamic
      compromise during PCI and a composite measure of major adverse events. Patients
      were followed for 30 days. No patient met the primary performance end point. Six
      safety end points in 5 patients occurred, including 1 access site complication
      requiring intervention, 1 cerebrovascular accident, 2 major bleeding
      complications, and 2 cases of new or worsening aortic insufficiency. No cardiac
      deaths, myocardial infarctions, or surgical interventions occurred. In
      conclusion, initial results of the HeartMate percutaneous heart pump for
      mechanical circulatory support during high-risk PCI are encouraging. Hemodynamic
      stability was achieved in all patients with a low incidence of adverse events.

PMID- 29655881
TI  - Racial Differences in Quality of Care and Outcomes After Acute Coronary Syndrome.
AB  - Guideline adherence and variation in acute coronary syndrome (ACS) outcomes by
      race in the modern era of drug-eluting stents (DES) are not well understood.
      Previous studies also fail to capture rapidly growing minority populations, such
      as Asians. A retrospective analysis of 689,238 hospitalizations for ACS across
      all insurance types from 2008 to 2011 from the Healthcare Cost and Utilization
      Project database was performed to determine whether quality of ACS care and
      mortality differ by race (white, black, Asian, Hispanic, or Native American),
      with adjustment for patient clinical and demographic characteristics and
      clustering by hospital. We found that black patients had the lowest in-hospital
      mortality rates (5% vs 6% to 7% for other races, p <0.0001, odds ratio [OR] 1.02,
      95% confidence interval [CI] 0.97 to 1.07), despite low rates of timely
      angiography in ST-elevation myocardial infarction and non-ST-elevation myocardial
      infarction, and lower use of DES (30% vs 38% to 40% for other races, p <0.0001).
      In contrast, Asian patients had the highest in-hospital mortality rates (7% vs 5%
      to 7% for other races, p <0.0001, odds ratio 1.13, 95% CI 1.08 to 1.20, relative
      to white patients), despite higher rates of timely angiography in ST-elevation
      myocardial infarction and non-ST-elevation myocardial infarction, and the highest
      use of DES (74% vs 63% to 68% for other races, p <0.0001). Asian patients had the
      worst in-hospital mortality outcomes after ACS, despite high use of early
      invasive treatments. Black patients had better in-hospital outcomes despite
      receiving less guideline-driven care.

PMID- 29655882
TI  - Incidence and Mortality of Adults With Pulmonary Hypertension and Congenital
      Heart Disease.
AB  - Reports on pulmonary hypertension (PH) in the aging congenital heart disease
      (CHD) population are few and focused on arterial PH and patients with systemic-to
      pulmonary shunts. Our objective was to estimate incidence and mortality of adult
      onset PH in the CHD population. Using Danish nationwide registries, we identified
      all patients diagnosed with CHD from 1963 to 1974 and 1977 to 2012. Patients were
      matched 1:10 by birth year and gender with general population subjects. Between
      1977 and 2013 adults >18 years of age were followed up until PH diagnosis, death,
      or emigration, whichever came first, using data from the Danish National Registry
      of Patients. We computed cumulative incidences of PH. Using Cox regression, we
      compared the mortality rate between CHD subjects with and without PH matched by
      gender and birth year. We identified 14,860 patients with CHD. At 70 years of
      age, their overall cumulative incidence of PH was 7.2% (8.3% in those with
      systemic-to-pulmonary shunts and 5.3% in those without) compared with 0.4% in the
      general population. The 1-, 5-, and 10-year mortality for adults with CHD and PH
      was 24%, 44%, and 52%, respectively. This represented a 4-fold (95% confidence
      interval 3.3 to 5.6) increase in mortality compared with adults with CHD without
      PH after adjusting for gender, birth year, CHD severity, and presence of
      extracardiac defects. In conclusion the incidence of PH was substantially
      increased in adults with CHD relative to the general population. Of note, the
      increased incidence was not limited to those with a history of systemic-to
      pulmonary shunts. PH was associated with increased mortality.

PMID- 29655883
TI  - Evaluating Surgical Coaching: A Mixed Methods Approach Reveals More Than Surveys
      Alone.
AB  - OBJECTIVE: Traditionally, surgical educators have relied upon participant survey
      data for the evaluation of educational interventions. However, the ability of
      such subjective data to completely evaluate an intervention is limited. Our
      objective was to compare resident and attending surgeons' self-assessments of
      coaching sessions from surveys with independent observations from analysis of
      intraoperative and postoperative coaching transcripts. DESIGN: Senior residents
      were video-recorded operating. Each was then coached by the operative attending
      in a 1:1 video review session. Teaching points made in the operating room (OR)
      and in post-OR coaching sessions were coded by independent observers using
      dialogue analysis then compared using t-tests. Participants were surveyed
      regarding the degree of teaching dedicated to specific topics and perceived
      changes in teaching level, resident comfort, educational assessments, and
      feedback provision between the OR and the post-OR coaching sessions. SETTING: A
      single, large, urban, tertiary-care academic institution. PARTICIPANTS: Ten PGY4
      to 5 general surgery residents and 10 attending surgeons. RESULTS: Although the
      reported experiences of teaching and coaching sessions by residents and faculty
      were similar (Pearson correlation coefficient = 0.88), these differed
      significantly from independent observations. Observers found that residents
      initiated a greater proportion of teaching points and had more educational needs
      assessments during coaching, compared to the OR. However, neither residents nor
      attendings reported a change between the 2 environments with regard to needs
      assessments nor comfort with asking questions or making suggestions. The only
      metric on which residents, attendings, and observers agreed was the provision of
      feedback. CONCLUSIONS: Participants' perspectives, although considered highly
      reliable by traditional metrics, rarely aligned with analysis of the associated
      transcripts from independent observers. Independent observation showed a distinct
      benefit of coaching in terms of frequency and type of learning points. These
      findings highlight the importance of seeking different perspectives, data
      sources, and methodologies when evaluating clinical education interventions.
      Surgical education can benefit from increased use of dialogue analyses performed
      by independent observers, which may represent a viewpoint distinct from that
      obtained by survey methodology.

PMID- 29655885
TI  - Short-term retrogradation behaviour of corn starch is inhibited by the addition
      of porcine plasma protein hydrolysates.
AB  - The potential inhibition of porcine plasma protein hydrolysates (PPPH) on the
      short-term retrogradation of corn starch (CS) was investigated. Compared with
      native CS, PPPH significantly enhanced breakdown and decreased the total setback
      in a rapid visco analyser (RVA) measurement (P < 0.05). Dynamic time sweep
      analysis of pre-prepared gelatinized samples showed a decrease in the storage
      modulus (G') and increase in the loss tangent (tan delta) in the presence of
      PPPH. Differential scanning calorimetry results showed that PPPH significantly
      reduced the gelatinization enthalpies (DeltaHg) and retrogradation enthalpies
      (DeltaHr) of CS (P < 0.05). Fourier transform infrared spectroscopy analysis
      indicated that the addition of PPPH decreased the amount of hydrogen bonds within
      starch. Low field nuclear magnetic resonance results showed that the addition of
      PPPH has an important role in increasing the mobility of water molecules and
      blocking the short-term retrogradation of CS. X-ray diffraction results showed
      that the peaks at 2theta close to 17-18 degrees  were progressively decreased to
      smaller angles with increasing PPPH concentrations. This phenomenon indicated
      that PPPH could interact with amylose and cause lattice distortion, which reduced
      the starch retrogradation. The results demonstrate that the addition of PPPH
      plays a crucial role in interfering with short-term retrogradation of CS.

PMID- 29655884
TI  - Lignin-based hydrogels with "super-swelling" capacities for dye removal.
AB  - Lignin is a complex natural polymer and it is one of the main constituent of the
      lignocellulosic biomass. Moreover, it is a bio-renewable material and it is
      available in large amounts as by-product from the forest industry. Lignin-based
      hydrogels with high swelling capabilities were prepared by crosslinking poly
      (methyl vinyl ether co-maleic acid) and different technical lignins in ammonium
      and sodium hydroxide solutions. The produced hydrogels showed a wide range of
      water absorption capacities varying from 13 to 130 g of water per 1 g of sample.
      It was observed that the higher the water uptake the poorer mechanical
      performance, as evaluated in terms of storage and loss modulus (G' and G",
      respectively) of the materials. Methylene blue (MB) was used as a model dye to
      evaluate the adsorption and release capabilities of the lignin hydrogels. Results
      suggested that these hydrogels showed a high MB removal efficiency, which ranged
      from 12 to 96%. On the contrary, the percentages of MB released depended on the
      negative surface charge of the hydrogels, showing values which ranged from 0.06
      to 0.35%. Thus, these materials have potential to be used as adsorbents for the
      removal of organic dyes from waste water.

PMID- 29655886
TI  - Lactobacillus hordei dextrans induce Saccharomyces cerevisiae aggregation and
      network formation on hydrophilic surfaces.
AB  - Water kefir granules are supposed to mainly consist of dextrans produced by
      Lactobacillus (L.) hilgardii. Still, other microorganisms such as L. hordei, L.
      nagelii, Leuconostoc (Lc.) citreum and Saccharomyces (S.) cerevisiae are commonly
      isolated from water kefir granules, while their contribution to the granule
      formation remains unknown. We studied putative functions of these microbes in
      granule formation, upon development of a simplified model system containing
      hydrophilic object slides, which mimics the hydrophilic surface of a growing
      kefir granule. We found that all tested lactic acid bacteria produced glucans,
      while solely those isolated from the four different L. hordei strains induced
      yeast aggregation on the hydrophilic slides. Therefore, structural differences
      between these glucans were investigated with respect to their size distributions
      and their linkage types. Beyond the finding that all glucans were identified as
      dextrans, those of the four L. hordei strains were highly similar among each
      other regarding portions of linkage types and size distributions. Thus, our study
      suggests the specific size and structural organization of the dextran produced by
      L. hordei as the main cause for inducing S. cerevisiae aggregation and network
      formation on hydrophilic surfaces and thus as crucial initiation of the stepwise
      water kefir granule growth.

PMID- 29655887
TI  - Engineering riboswitch in L. major: From prediction to conceptualization.
AB  - Post-transcriptional gene regulation is a vital process to regulate expression of
      the key genes in the eukaryotic cell. Such processes are essential for pathogens
      which reside inside the host cell. One such pathogen is Leishmania major, which
      causes cutaneous leishmaniasis. The parasite lives inside the macrophages of
      mammalian host (mostly human). Inside the macrophage, Leishmania genes show
      complex host-pathogen interaction regulating a plethora of gene expression. Till
      date, most of the studies have shown this kind of regulation with respect to the
      host macrophages. Here, based on an extensive in silico analysis, we have
      hypothesized a novel Theophylline binding riboswitch mediated post
      transcriptional regulation of a gene i.e. RNA Polymerase III subunit1
      (Lmjf_09_1060), an essential gene for the parasite's survival both in its
      promastigote as well as in its amastigote form. Later, we have conceptualized the
      working of the identified putative Theophylline binding riboswitch cassette in in
      vitro using E. coli based reporter assay, wherein, a reporter gene (eGFP) is used
      instead of RNA Polymerase III subunit1 gene and apparently have shown the
      downregulation of the reporter gene (eGFP) expression under the influence of in
      silico identified Theophylline binding riboswitch.

PMID- 29655888
TI  - Preparation and characterization of new low cost adsorbent beads based on
      activated bentonite encapsulated with calcium alginate for removal of 2,4
      dichlorophenol from aqueous medium.
AB  - This study explored the potential of composites organo-bentonite/alginate beads
      as adsorbents for the removal of 2,4-dichlorophenol (2,4DCP) from aqueous
      solution. Bentonite was firstly modified with cationic surfactants
      octadecyltrimethylammonium, hexadecyl trimethylammonium and
      phenyltrimethylammonium, then encapsulated with calcium alginate to form
      adsorbent composite beads. X-ray diffraction was used to study the change in the
      structural properties of the samples. The intercalated cationic surfactants were
      characterized by Fourier transform infrared spectroscopy (FTIR). The adsorption
      was studied using various operating parameters such as contact time, temperature,
      pH and initial 2,4DCP concentration. The results showed that the amount of 2,4DCP
      increased with increasing initial concentration, contact time and temperature
      indicating that the adsorption process of 2,4DCP onto composites is endothermic.
      Adsorption of 2,4DCP followed pseudo-second-order kinetics. The Langmuir isotherm
      model fitted well the isotherm data, indicating a monolayer homogeneous
      adsorption. The prepared adsorbents exhibited relatively high adsorption capacity
      of 142 to 391 mg/g founded by this model.

PMID- 29655889
TI  - Composition characterization, antioxidant capacities and anti-proliferative
      effects of the polysaccharides isolated from Trametes lactinea (Berk.) Pat.
AB  - This study was designed to investigate the chemical characterization and
      bioactivity of the Trametes lactinea (Berk.) Pat polysaccharides (TLP). The crude
      TLP was fractionated into two fractions, namely TLP-1 and TLP-2 with Cellulose
      DEAE-52 and Sephadex G-150. HPLC and FT-IR analysis showed that TLP-1 and TLP-2
      were heteropolysaccharides mainly composed of glucose with the average molecular
      weights of 443.19kDa and 388.83kDa, respectively. TLP-1 from water elution
      possessed of higher reducing power and scavenging activities against 1,1-diphenyl
      2-picrylhydrazyl (DPPH) radical, superoxide radical and hydroxyl radical than TLP
      2 eluted by 0.1M of NaCl. In comparison with TLP-2, TLP-1 showed stronger growth
      inhibition against human hepatoblastoma HepG-2 cells and caused higher LDH
      leakage. However, TLP-1 showed lower growth inhibition against normal hepatocyte
      L-02 cells and lower LDH leakage than TLP-2. Flow cytometric analysis showed that
      TLP-1 had a stimulatory effect on apoptosis of HepG-2 cells. These findings
      suggested that the polysaccharides, especially TLP-1 could contribute to the
      potential anticancer effects of T. lactinea (Berk.) Pat, which might be valuable
      as a natural antioxidant source applied in both healthy medicine and food
      industry for health benefits.

PMID- 29655890
TI  - Comprehensive Imaging and Surgical Review of Urinary Diversions: What the
      Radiologist Needs to Know.
AB  - Urinary diversions are surgical procedures that reconstruct the lower urinary
      tract following cystectomy. The 2 common surgical approaches are based on the
      continence status of the urinary tract. Incontinent diversions have continuous
      urine drainage through a cutaneous stoma, whereas continent diversions offer the
      patient the ability to self-void either via stoma catheterization or with the
      patient's own urethra. Given the large number of diversion procedures available,
      postsurgical anatomy may be complex. Multiple imaging modalities can be used to
      assess the postprocedural anatomy, potential complications, and for on-going
      oncologic monitoring. The purpose of this review is to describe the common
      surgical techniques and associated complications.

PMID- 29655891
TI  - The 9 Habits of Highly Effective Radiologists.
AB  - Stephen R. Covey's landmark work in the field of effectiveness and professional
      development delineated first 7, then ultimately eight, habits of highly effective
      people with applicability to all professions.1 This article describes the eight
      habits in specific relation to the radiologist, and proposes a ninth habit to
      help one bring a positive and centered approach during the journey to
      effectiveness and beyond.

PMID- 29655892
TI  - A case report and review of the literature indicate that HMGA2 should be added as
      a disease gene for Silver-Russell syndrome.
AB  - Patients with Silver-Russell syndrome (SRS), a syndromic growth retardation
      syndrome, usually harbor an epimutation at chromosome 11p15 or a maternal
      uniparental disomy of chromosome 7. However, to date the genetic cause remains
      unknown in around 40% of SRS cases, suggesting genetic heterogeneity and
      involvement of other genes. We present a 4-year-old female patient with the
      clinical diagnosis of SRS and negative results in common genetic SRS diagnostics.
      Whole exome sequencing identified a de novo heterozygous 7.3 kb deletion on
      chromosome 12q14.3 including exon 1 and 2 of HMGA2. HMGA2 encodes an
      architectural transcription factor and has already been linked to body size
      variations in various genome-wide association studies and mouse models. Reviewing
      the literature, we found additional four patients with a phenotype of SRS
      harboring point mutations or structural variants involving HMGA2. We conclude
      that genetic testing of HMGA2 should be considered in routine diagnostics in
      patients with the suspicion of SRS.

PMID- 29655893
TI  - Comparative sequence and structural analysis of Indian orf viruses based on major
      envelope immuno-dominant protein (F1L), an homologue of pox viral p35/H3 protein.
AB  - Orf virus (ORFV), a member of the genus Parapoxvirus in the family Poxviridae, is
      the cause of orf, a highly contagious zoonotic viral disease that affects mainly
      sheep and goats. In the present study, the sequence and phylogenetic analysis of
      Indian ORFV isolates (n = 15) from natural outbreaks in sheep and goats belonging
      to different geographical regions were analysed on the basis of F1L gene along
      with homology modelling of F1L protein. Multiple sequence alignments revealed
      highly conserved C-terminus and heterogeneity of N-terminus region of F1L among
      all orf viruses studied. Further, a comparative sequence alignment indicated
      conservation of various motifs such as glycosaminoglycan (GAG), Asp/Glu-any
      residue-Asp (D/ExD) and a Cx3C chemokine like motif among all poxviruses and
      unique motifs (proline rich region [PRR] and Lys-Gly-Asp [KGD]), in
      parapoxviruses including ORFV isolates irrespective of geography and host
      species. Phylogenetically, two major clusters were noticed which included Indian
      orf isolates along with foreign isolates. Structurally, ORFV F1L resembled the
      topology as exhibited by its homologue vaccinia virus H3 protein with mixed
      beta/alpha folds and ligand binding specificity in docking models. We noted that
      despite differences in host cell specificity and pathogencity, poxvirus proteins
      especially ORFV F1L protein and its homologues presumed to share similarities as
      they are highly conserved irrespective of species and countries of origin.
      Further, the study also indicated the possibilities of differentiation of ORFV
      strains based on N-terminal heterogeneity despite highly conserved C-terminal
      region with conserved motifs.

PMID- 29655894
TI  - HHIPL-1 (rs2895811) gene polymorphism is associated with cardiovascular risk
      factors and cardiometabolic parameters in Mexicans patients with myocardial
      infarction.
AB  - Several studies have reported the role of hedgehog interacting protein-like 1
      (HHIPL-1) in different pathologies, including cardiovascular disease. The aim of
      the present study was to analyze the association of HHIPL-1 (rs2895811)
      polymorphism with myocardial infarction (MI), cardiometabolic parameters, and
      traditional cardiovascular risk factors in the Mexican population. The
      polymorphism was genotyped using a TaqMan assay in 1023 patients with MI and 1105
      controls. A similar distribution of the polymorphism was observed between studied
      groups. However, in patients group, the C allele was associated with a decreased
      risk of developing hypertriglyceridemia (OR = 0.757, Padditive = 0.030, OR =
      0.685, Pdominant = 0.020, OR = 0.691, Pcodominant1 = 0.030), metabolic syndrome
      (OR = 0.746, Padditive = 0.030, OR = 0.647, Pdominant = 0.005, OR = 0.670,
      Pheterozygote = 0.015, OR = 0.637, Pcodominant1 = 0.005), and insulin resistance
      (OR = 0.681, Pdominant = 0.045). The results suggest that HHIPL-1 rs2895811
      polymorphism is associated with cardiometabolic parameters in Mexican patients
      with MI.

PMID- 29655895
TI  - Exploring the loblolly pine (Pinus taeda L.) genome by BAC sequencing and Cot
      analysis.
AB  - Loblolly pine (LP; Pinus taeda L.) is an economically and ecologically important
      tree in the southeastern U.S. To advance understanding of the loblolly pine (LP;
      Pinus taeda L.) genome, we sequenced and analyzed 100 BAC clones and performed a
      Cot analysis. The Cot analysis indicates that the genome is composed of 57, 24,
      and 10% highly-repetitive, moderately-repetitive, and single/low-copy sequences,
      respectively (the remaining 9% of the genome is a combination of fold back and
      damaged DNA). Although single/low-copy DNA only accounts for 10% of the LP
      genome, the amount of single/low-copy DNA in LP is still 14 times the size of the
      Arabidopsis genome. Since gene numbers in LP are similar to those in Arabidopsis,
      much of the single/low-copy DNA of LP would appear to be composed of DNA that is
      both gene- and repeat-poor. Macroarrays prepared from a LP bacterial artificial
      chromosome (BAC) library were hybridized with probes designed from cell wall
      synthesis/wood development cDNAs, and 50 of the "targeted" clones were selected
      for further analysis. An additional 25 clones were selected because they
      contained few repeats, while 25 more clones were selected at random. The 100 BAC
      clones were Sanger sequenced and assembled. Of the targeted BACs, 80% contained
      all or part of the cDNA used to target them. One targeted BAC was found to
      contain fungal DNA and was eliminated from further analysis. Combinations of
      similarity-based and ab initio gene prediction approaches were utilized to
      identify and characterize potential coding regions in the 99 BACs containing LP
      DNA. From this analysis, we identified 154 gene models (GMs) representing both
      putative protein-coding genes and likely pseudogenes. Ten of the GMs (all of
      which were specifically targeted) had enough support to be classified as intact
      genes. Interestingly, the 154 GMs had statistically indistinguishable (alpha =
      0.05) distributions in the targeted and random BAC clones (15.18 and 12.61 GM/Mb,
      respectively), whereas the low-repeat BACs contained significantly fewer GMs
      (7.08 GM/Mb). However, when GM length was considered, the targeted BACs had a
      significantly greater percentage of their length in GMs (3.26%) when compared to
      random (1.63%) and low-repeat (0.62%) BACs. The results of our study provide
      insight into LP evolution and inform ongoing efforts to produce a reference
      genome sequence for LP, while characterization of genes involved in cell wall
      production highlights carbon metabolism pathways that can be leveraged for
      increasing wood production.

PMID- 29655896
TI  - Differential expression profile of long non-coding RNA in the stenosis tissue of
      arteriovenous fistula.
AB  - OBJECTIVE: To analyze and preliminarily validate the lncRNA expression profiles
      in the stenosis tissue of arteriovenous fistula (AVF). METHODS: A total of 54
      uremic patients administered in the department of nephrology in the First
      Affiliated Hospital of Nanchang University between February 2017 and March 2017
      were included in the study and subsequently categorized as experimental group,
      which included 12 patients with confirmed diagnosis of AVF, and control group
      which included 42 patients with no vascular stenosis. The experimental group
      inclusion criteria include: AVF used >3 months; The blood flow of AVF <200
      mL/min; the degree of the stenosis was >50%, excluded obvious thrombosis; The
      ultrasonographic data of AVF stenosis is complete. The controls were randomly
      selected from uremic patients who were primary AVF operation, excluded obvious
      vascular stenosis and vascular diseases. Among them, 4 sample in the experimental
      group and 4 controls were used in LncRNA sequencing. RNA in vascular tissue was
      extracted by Trizol and IncRNA sequencing was used to establish the expression
      profiles of lncRNA in the stenosis tissue of AVF.9 difference expression lncRNA
      were collected for validating in AVF stenosis cases by using quantitative real
      time polymerase chain reaction (qRT-PCR). Moreover, Cluster analysis, gene
      functional analysis and pathway analysis were used to explore the function of
      difference expression lncRNA. RESULTS: Among the 27,692 lncRNA transcripts
      examined, 247 lncRNAs were found to be significantly differentially expressed (P
      < 0.05, fold change >=2) in the experimental group and control group, with 141
      being up-regulated and 106 down-regulated. The expression levels of 9 lncRNAs
      validated by subsequent qRT-PCR were shown to be highly consistent with the
      sequencing data. CONCLUSION: Our study revealed lncRNAs expression profiles in
      the stenosis tissue of AVF by LncRNA sequencing. These lncRNAs and its related
      signaling pathways may play a key role in the occurrence and progression of AVF
      stenosis.

PMID- 29655897
TI  - Adsorption removal of natural organic matters in waters using biochar.
AB  - This work concerns the adsorption of aromatic organic matter from river water
      using various doses of a simulated biochar. The water yielded five UV254 peaks
      associated with organic matters in size exclusion chromatography (SEC),
      corresponding to molecular weights (MW) of 10,000, 6500, 4800, 3000, and 1500 Da.
      Biochar removes all of these peaks with an overall adsorption of 6.4 mg-DOC/g-C,
      and preferentially removes organic matter with high MW. Physisorption control in
      a pseudo-second-order type model fits the adsorption kinetics. Biochar can
      therefore be used as an efficient adsorbent of organic matter in water.

PMID- 29655898
TI  - Efficient biocatalytic synthesis of nicotinic acid by recombinant nitrilase via
      high density culture.
AB  - The constitutively expression system for P. putida nitrilase was firstly
      constructed to improve the nicotinic acid production and reduce the production
      costs. High density culture strategy was employed to enhance the biomass and
      nitrilase production of recombinant strain. The total nitrilase activity reached
      up to 654 U.mL-1 without the induction. 541 g.L-1 nicotinic acid was accumulated
      via fed batch mode of substrate feeding through 290 min of conversion.

PMID- 29655899
TI  - Value-added biotransformation of cellulosic sugars by engineered Saccharomyces
      cerevisiae.
AB  - The substantial research efforts into lignocellulosic biofuels have generated an
      abundance of valuable knowledge and technologies for metabolic engineering. In
      particular, these investments have led to a vast growth in proficiency of
      engineering the yeast Saccharomyces cerevisiae for consuming lignocellulosic
      sugars, enabling the simultaneous assimilation of multiple carbon sources, and
      producing a large variety of value-added products by introduction of heterologous
      metabolic pathways. While microbial conversion of cellulosic sugars into large
      volume low-value biofuels is not currently economically feasible, there may still
      be opportunities to produce other value-added chemicals as regulation of
      cellulosic sugar metabolism is quite different from glucose metabolism. This
      review summarizes these recent advances with an emphasis on employing engineered
      yeast for the bioconversion of lignocellulosic sugars into a variety of non
      ethanol value-added products.

PMID- 29655900
TI  - The anterolateral ligament is a distinct ligamentous structure: A histological
      explanation.
AB  - BACKGROUND: The aim was to determine whether the anterolateral ligament (ALL) had
      a histological structure that defined it as a real ligament. METHODS:
      Histological examination of 30 ALL samples taken from fresh-frozen knees were
      performed. The ALL femoral insertion and its relationship with the lateral
      collateral ligament (LCL) were studied and the tibial insertion and its
      relationship with articular cartilage of the tibial joint surface were analyzed.
      For the ligamentous part, its histological structure and its differences with the
      articular capsule were studied. RESULTS: This connective tissue is composed of a
      dense fibrous core constituted by a network of oriented collagenous fibers. The
      periphery of this dense connective center is made up of loose fibrocollagenous
      tissue with vascular structures and focal deposits of adipose tissue. This part
      was in contact but different to the joint capsule. With a perpendicular
      orientation of the collagen fibers relative to the bone, a fibrocartilaginous
      zone with an unmineralized hyalinized aspect, a mineralization front, its bone
      insertions presented a typical ligamentous insertion. With a cleavage plane
      between ALL and LCL femoral insertion, the ALL appeared to have a femoral
      insertion distinct from the LCL. ALL tibial insertion was less characteristic
      with less organized connective tissue and was at a distance from the articular
      cartilage. CONCLUSION: From its bony insertion to its tissue composition and
      organization, the ALL has all the histological characteristics of a ligamentous
      structure. Our study confirms that ALL can be considered a real and distinct
      ligament.

PMID- 29655901
TI  - In vivo heterotopic culturing of prefabricated tendon grafts with mechanical
      stimulation in a sheep model.
AB  - BACKGROUND: The goal of this study is to investigate the biomechanical and
      histological properties of in vivo heterotopically prefabricated cruciate
      ligament replacement grafts with and without mechanical stimulation. The clinical
      goal is to heterotopically prefabricate a bone-tendon-bone graft for anterior
      cruciate ligament reconstruction, which allows rapid ingrowth and early full
      weight bearing. METHODS: In a sheep model, eight quadriceps tendon grafts were
      harvested and introduced into culture chambers at their proximal and distal ends.
      In group S, four tendon-chamber constructs were mechanically stimulated by direct
      attachment to the quadriceps tendon and patella. In group NS, the same constructs
      were cultured without proximal attachment. All sheep were sacrificed six weeks
      postoperatively and the constructs were examined biomechanically and
      histologically. The healthy contralateral ACL and quadriceps tendon were used as
      controls. RESULTS: Macroscopically, no obvious ossification could be observed at
      the ends of the tendon-chamber constructs six weeks postoperatively.
      Histologically, the tendon tissue from the mechanically stimulated constructs
      revealed higher counts of cells and capillaries. However, there was less regular
      cell distribution and collagen fiber orientation compared to the control group.
      In addition, osteoblasts and osteogenesis were observed in the prefabricated
      constructs both with and without mechanical stimulation. Biomechanically, there
      were no significant differences in stiffness, elongation and ultimate failure
      load between the groups. CONCLUSION: In vivo heterotopic culture of prefabricated
      tendon grafts may have the potential to stimulate osteoblasts and induce
      osteogenesis. Future studies with longer follow-up and modifications of the
      surgical technique and culture conditions are desirable.

PMID- 29655902
TI  - Association between increase in vertical ground reaction force loading rate and
      pain level in women with patellofemoral pain after a patellofemoral joint loading
      protocol.
AB  - BACKGROUND: The etiology of patellofemoral pain (PFP) is thought to be the result
      of increased patellofemoral joint (PFJ) load and aberrant lower extremity
      mechanics, including altered vertical ground reaction forces (VGRF). However, few
      studies have investigated the association between an increase in pain and VGRF
      loading rates in the context of PFP. Thus, this study aimed to investigate the
      immediate effects of PFJ loading on pain and VGRF loading rate, and to see if
      there is a link between modification of both pain and VGRF loading rate during
      stair negotiation. METHODS: Thirty-four women with PFP underwent VGRF analysis
      during stair negotiation under two conditions: with (condition 2) and without
      (condition 1) being previously submitted to a PFJ loading protocol in order to or
      not to exacerbate their knee pain, respectively. RESULTS: The VGRF loading rates
      were significantly higher in condition 2 (Mean +/- standard deviation (SD)=4.0+/
      0.6N/s) compared to condition 1 (Mean+/-SD=3.6+/-0.5N/s) during stair ascent and
      during stair descent (Mean+/-SD: condition 1=6.3+/-1.1N/s; condition 2=7.0+/
      1.4N/s). In addition, VGRF loading rates were higher during stair descent
      compared to stair ascent in both conditions. There were significant correlations
      between the increase in pain and VGRF loading rate during both tasks. CONCLUSION:
      There seemed to be an important relation between the increase in pain and VGRF
      loading rates in women with PFP. Based on these findings, interventions aimed at
      reducing VGRF loading rates are important in the context of PFP.

PMID- 29655903
TI  - Valid assessment of women's satisfaction with breast cancer screening programs.

PMID- 29655904
TI  - 3D printed, controlled release, tritherapeutic tablet matrix for advanced anti
      HIV-1 drug delivery.
AB  - PURPOSE: A 3D-Bioplotter(r) was employed to 3D print (3DP) a humic acid
      polyquaternium 10 (HA-PQ10) controlled release fixed dose combination (FDC)
      tablet comprising of the anti-HIV-1 drugs, efavirenz (EFV), tenofovir disoproxil
      fumarate (TDF) and emtricitabine (FTC). METHODS: Chemical interactions, surface
      morphology and mechanical strength of the FDC were ascertained. In vitro drug
      release studies were conducted in biorelevant media followed by in vivo study in
      the large white pigs, in comparison with a market formulation, Atripla(r). In
      vitro-in vivo correlation of results was undertaken. RESULTS: EFV, TDF and FTC
      were successfully entrapped in the 24-layered rectangular prism-shaped 3DP FDC
      with a loading of ~12.5 mg/6.3 mg/4 mg of EFV/TDF/FTC respectively per printed
      layer. Hydrogen bonding between the EFV/TDF/FTC and HA-PQ10 was detected which
      was indicative of possible drug solubility enhancement. The overall surface of
      the tablet exhibited a fibrilla structure and the 90 degrees  inner pattern was
      determined to be optimal for 3DP of the FDC. In vitro and in vivo drug release
      profiles from the 3DP FDC demonstrated that intestinal-targeted and controlled
      drug release was achieved. CONCLUSION: A 3DP FDC was successfully manufactured
      with the aid of a 3D-Bioplotter in a single step process. The versatile HA-PQ10
      entrapped all drugs and achieved an enhanced relative bioavailability of EFV,
      TDF, and FTC compared to the market formulation for potentially enhanced HIV
      treatment.

PMID- 29655905
TI  - Functional relevance of synonymous alleles reflected in allele rareness in the
      population.
AB  - We provide theoretical evidence supporting the non-neutrality of synonymous
      alleles by investigating the rareness of synonymous alleles in the population. We
      find a significantly greater number of synonymous rare alleles than conventional
      neutral alleles derived from noncoding regions. A permutation experiment shows
      that the rareness of synonymous alleles is not a byproduct of random statistical
      noise. We then compare the frequencies of synonymous rare alleles and common
      alleles in various functional contexts in which synonymous alleles are known to
      be involved. Subsequently, we perform logistic regression analysis to elucidate
      the effect size of each independent factor contributing to the rareness of
      synonymous alleles. Additionally, we show that changes in optimality caused by
      synonymous mutations resulting in rare SNPs in the population tend to be biased
      toward optimality loss. We think that our study will contribute to the
      development of novel strategies for identifying functional synonymous mutations.

PMID- 29655906
TI  - Substance Use and Sex Index (SUSI): First stage development of an assessment tool
      to measure behaviour change in sexualised drug use for substance use treatment
      studies.
AB  - BACKGROUND: Existing tools for measuring blood-borne virus (BBV) and sexually
      transmitted infection (STI) transmission risk behaviours in substance use
      interventions have limited capacity to assess risk behaviours across varied
      social, cultural and epidemiological contexts; have not evolved alongside HIV
      treatment and prevention innovations; or accounted for sexual contexts of drug
      use including among a range of lesbian, gay, bisexual, transgender, intersex and
      queer (LGBTIQ) sub-communities. The Substance Use and Sex Index (SUSI) is a new
      brief, simple tool being developed to assess change in HIV and STI risk
      behaviours for substance use treatment studies. METHODS: A 26-item questionnaire
      was piloted online among community volunteers (n = 199). Concurrent and
      predictive validity were assessed against risk-taking (RT-18) and STI testing
      items (Gay Community Periodic Surveys). RESULTS: The developed scale comprised
      nine items measuring: condomless penile (anal or vaginal) sex, unprotected oral
      sex, shared toy use, bloodplay, chemsex (consumption of drugs for the
      facilitation of sex), trading sex for drugs, being 'too out of it' to protect
      self, injecting risk and group sex. Factor-analytic approaches demonstrated that
      items met good fit criteria for a single scale. Significant, moderate magnitude,
      positive relationships were identified between total SUSI score and both RT-18
      risk-taking and recent STI testing. Qualitative feedback underscored the
      importance of culturally-embedded question formulation. CONCLUSION: The results
      support the conceptual basis for the instrument, highlighting the need for
      further scale content refinement to validate the tool and examine sensitivity to
      change. SUSI is a step towards improving outcome measurement of HIV/BBV/STI
      transmission risk behaviours in substance use treatment studies with greater
      inclusiveness of experiences across different population groups.

PMID- 29655907
TI  - Improving the Visibility of Intravenous (IV) Site in Pediatric Patients to Reduce
      IV Site Related Complications - An Evidence-based Utilization Project.
AB  - PURPOSE: This project aims to improve the visibility of the IV site using more
      adhesive transparent dressings to attain 90% compliance based on the frequent and
      proper inspection of the IV site and decrease the incidence of IV complications.
      DESIGN AND METHOD: The project was conducted in a 43-bedded general pediatric
      ward from March 2016 to February 2017. To address the poor visibility of the IV
      site due to bandaging caused by poor adhesive strength of the IV securement
      dressing, a more adhesive securement dressing was introduced. The study team
      conducted pre-implementation, immediate post-implementation, and sustainment
      audits, cost-analysis, and comparison of the number of reported occurrences of
      phlebitis and extravasation between 2015 and 2017. RESULTS: The post
      implementation audit showed 100% visibility of the IV site, from 73% pre
      implementation, and 87% compliance on frequent IV site inspection, from 70% pre
      implementation. Both criteria attained 100% compliance during the sustainment
      audit. Incidences of extravasation and phlebitis were reduced from eight to
      seven, an improvement of 13%. These seven cases were also generally less severe
      compared to those from the previous year. CONCLUSION: This project has greatly
      improved the visibility of the IV site as well as nurses' compliance in checking
      the IV site. This is because nurses can monitor the IV site without having to
      remove any additional bandage over the site and causing unnecessary distress to
      fretful pediatric patients. IMPLICATIONS: The use of an adhesive transparent
      dressing can lead to prevention and earlier detection of phlebitis and
      extravasation. Additionally, the new IV securement dressing brought about
      manpower cost savings enabling staff time directed to other patient care
      activities.

PMID- 29655908
TI  - Virtual special issue: Endocrine.

PMID- 29655909
TI  - Carbon catabolite repression gene creA regulates morphology, aflatoxin
      biosynthesis and virulence in Aspergillus flavus.
AB  - Carbon catabolite repression (CCR) is a very important mechanism employed in the
      utilization of carbon as an energy source, required for the regulation of growth,
      development and secondary metabolite production in fungi. Despite the wide study
      of this mechanism in fungi, little is known about the major CCR gene creA in A.
      flavus. Hence, we report identification of A. flavus carbon catabolite repression
      gene creA, which is responsible for the repression of secondary carbon sources.
      Gene deletion and over-expression was employed to explicate the role of creA in
      the morphology, pathogenicity, and secondary metabolite production in A. flavus.
      We investigated these factors using three carbon sources including glucose,
      sucrose and maltose. Gene deletion mutant (DeltacreA) had a significant growth
      defect on complete medium and minimal medium containing maltose. Conidia
      production in DeltacreA was significantly impaired irrespective of the carbon
      source available, while sclerotia production was significantly increased,
      compared to wild type (WT) and over-expression strain (OE::creA). Importantly,
      DeltacreA produced insignificant amount of aflatoxin in complete medium, and its
      ability to colonize hosts was also impaired. Concisely, we showed that creA
      played an important role in the morphology, pathogenicity and secondary
      metabolite production of A. flavus.

PMID- 29655910
TI  - Cardiac voltage-gated sodium channel expression and electrophysiological
      characterization of the sodium current in the zebrafish (Danio rerio) ventricle.
AB  - Na+ channel alpha-subunit composition of the zebrafish heart and
      electrophysiological properties of Na+ current (INa) of zebrafish ventricular
      myocytes were examined. Eight Na+ channel alpha-subunits were expressed in both
      atrium and ventricle of the zebrafish heart. Nav1.5Lb, an orthologue to the human
      Nav1.5, was clearly the predominant isoform in both chambers representing 65.2 +/
      4.1% and 83.1 +/- 2.1% of all Na+ channel transcripts in atrium and ventricle,
      respectively. Nav1.4b, an orthologue to human Nav1.4, formed 34.1 +/- 4.1 and
      16.2 +/- 2.0% of the Na+ channel transcripts in atrium and ventricle,
      respectively. The density of INa and the rate of action potential upstroke in
      zebrafish ventricular myocytes at 28  degrees C were similar to those of human
      ventricles at the comparable temperature. Na+ channel isoforms and the main
      electrophysiological characteristics of the INa are largely similar in zebrafish
      and human hearts indicating evolutionary conservation of Na+ channel composition
      and function. The zebrafish INa differs from the human cardiac INa in terms of
      higher tetrodotoxin sensitivity (IC50-value = 5.3 +/- 0.1 nM) and slower
      inactivation kinetics. The zebrafish INa was inhibited with tricaine (MS-222)
      with an IC50-value of 1.2 +/- 0.18 mM (336 mg l-1), suggesting some care in the
      use of MS-222 as an anesthetic.

PMID- 29655911
TI  - Antinociceptive activity of Riparin II from Aniba riparia: Further elucidation of
      the possible mechanisms.
AB  - Riparin II (RipII) has an anti-inflammatory activity potentially due its ability
      to decrease TNF-alpha and IL-1beta production and its histamine antagonism. The
      objective of this study was to evaluate the role of RipII in the pain process and
      the possible antinociceptive mechanisms involved, using classic models of
      nociception. Male Swiss mice were used in the assays. Determinate the acute
      toxicity according to the OECD 425 test guideline. The models used were the
      acetic acid-, formalin-, hot plate and glutamate-induced nociception. For
      evaluation of antinociceptive effect, the involvement of TRPV1, TRPA1, TRPM8,
      ASICS, Bradykinin, PKC and PKA were performed using the paw licking using
      agonists. The acute toxicity study did not detect any clinical signs or changes
      in behavior or mortality. RipII, administered orally (25 and 50 mg/kg) caused a
      reduction of nociception induced by acetic acid, formalin (on the second phase)
      and glutamate. In the investigation of antinociceptive mechanism, we used
      capsaicin (2.2 MUg/paw), cinnamaldehyde (10 nmol/paw), menthol (1.2 MUmol/paw),
      ASICS (2% acetic acid, pH 1.98) and bradykinin (10 MUg/paw). The results showed
      that TRPV1, TRPA1, TRPM8, ASICS and bradykinin play a role in the antinociceptive
      effect of RipII. The results also showed that PKA is involved too. These data
      demonstrate that RipII has a low or not toxicity and produced an important
      antinociceptive effect through mechanisms that probably involve an interaction,
      at least in part, TRPV1, TRPA1, TRPM8, ASICS, bradykinin and PKA participate in
      the RipII's antinociceptive effect.

PMID- 29655912
TI  - Argemone oil, an edible oil adulterant, induces systemic immunosuppression in
      Balb/c mice in an oral 28 days repeated dose toxicity study.
AB  - Consumption of edible oils contaminated with Argemone oil (AO) leads to a
      clinical condition called "Epidemic dropsy". Earlier studies have reported that
      metabolism and oxidative stress primarily contributes to AO toxicity, however,
      the involvement of immune system has not been assessed so far. Therefore, the
      present study was undertaken to systematically assess the effect of AO exposure
      on the function of immune system in Balb/c mice. The repeated exposure of AO for
      28 days caused prominent regression of spleen and thymus; severe inflammatory
      changes in spleen depicted by the loss of distinct follicles, increased
      megakaryocyte infiltration, and enhanced expression levels of inflammatory
      markers (iNOS & COX-2). At the functional level, AO exposure significantly
      abrogated the mixed lymphocyte reaction and mitogen-stimulated
      lymphoproliferative activity of T and B cells, which is reflective of profound
      lymphocyte dysfunction upon antigen exposure. In concordance with the loss in
      functional activity of lymphocytes in AO exposed animals, it was found the AO
      altered the relative percentage of CD3+, CD4+, and CD28 + T cells. Further, there
      was a marked decrease in the relative distribution of cells with prominent MHC I
      and CD1d expression in AO exposed splenocytes. Moreover, reduced levels of immune
      stimulatory cytokines (TNF-alpha, IFN-gamma, IL-2, IL-4, and IL-6), and increased
      levels of immunosuppressive cytokine IL-10 were detected in the serum of AO
      treated mice. Along with T and B cells, AO exposure also affected the phenotype
      and activation status of macrophages suggesting the inclination towards
      "alternative activation of macrophages". Altogether, these functional changes in
      the immune cells are contributing factors in AO induced immunosuppression.

PMID- 29655913
TI  - Germacrone reverses adriamycin resistance in human chronic myelogenous leukemia
      K562/ADM cells by suppressing MDR1 gene/P-glycoprotein expression.
AB  - Multidrug resistance (MDR) usually causes chemotherapy failure of chronic
      myelogenous leukemia (CML). Germacrone is a terpenoid compound and has been
      reported to reverse MDR in breast cancer cells. However, the effect of germacrone
      on MDR in CML cells was unknown. The aim of the present study was to evaluate the
      effect of germacrone on MDR in adriamycin resistance of CML cells. Treatment with
      a combination of germacrone and adriamycin synergistically inhibited the
      viability and increased LDH release in K562/ADM cells. Adriamycin induced the
      apoptosis and caspase-3 activity of K562/ADM cells, and the germacrone treatment
      significantly enhanced the induction. Adriamycin treatment inhibited the
      expression of Bcl-2 and induced the expression of Bax, and germacrone enhanced
      the effect of adriamycin. Germacrone decreased adriamycin-induced expression of
      MDR1 mRNA and P-gp protein. Overexpression of P-glycoprotein (P-gp) reversed the
      effect of germacrone on adriamycin resistance in K562/ADM cells. In conclusion,
      germacrone reversed adriamycin resistance in human chronic myelogenous leukemia
      K562/ADM cells by suppressing MDR1 gene/P-gp expression. The results indicated
      that germacrone might be a new MDR reversal agent for CML chemotherapy.

PMID- 29655914
TI  - Importance of cynomolgus monkeys in development of monoclonal antibody drugs.
AB  - Animal species used in the preclinical studies for development of monoclonal
      antibody (mAb) drugs are surveyed in this review. Relevant animal species for
      preclinical studies of mAb candidates are those express desired epitope of mAb
      candidates. Cynomolgus monkeys cross-react with mAb drugs much higher than other
      animal species commonly used in preclinical studies such as absorption,
      distribution, metabolism and excretion (ADME), efficacy, and toxicity studies,
      for development of new drugs. Moreover, plasma exposure of the mAb drugs in
      humans is predicted well from the exposure in the monkeys, and the placental
      transfer of immunoglobulin G (IgG, all the mAb drugs contain IgG) from mother to
      fetus is similar between humans and the monkeys from a viewpoint of time course
      and plasma level of IgG transferred. These observed findings indicate that the
      monkeys are the most suitable animal species used in the ADME and toxicity
      studies for development of new mAb drugs.

PMID- 29655915
TI  - Real-time monitoring of pH-dependent intracellular trafficking of ovarian cancer
      G protein-coupled receptor 1 in living leukocytes.
AB  - G-protein coupled receptors (GPCRs) are involved in many diseases and important
      biological phenomena; elucidating the mechanisms underlying regulation of their
      signal transduction potentially provides both novel targets for drug discovery
      and insight into living systems. A proton-sensing GPCR, ovarian cancer G protein
      coupled receptor 1 (OGR1), has been reported to be related to acidosis and
      diseases that cause tissue acidification, but the mechanism of proton-induced
      activation of OGR1-mediated signal transduction in acidic conditions remains
      unclear. Here, pH-dependent intracellular trafficking of OGR1 was visualized in
      living leukocytes by a real-time fluorescence microscopic method based on sortase
      A-mediated pulse labeling of OGR1. OGR1 labeled on the cell surface with a small
      fluorescent dye was clearly observed to remain in the plasma membrane during
      incubation in mildly acidic medium (pH 6.6) and to be internalized to the
      intracellular compartments on changing the medium to slightly basic pH (7.7).
      Quantitative single-cell image analysis showed that most of the internalized
      OGR1s were then recycled to the plasma membrane for signal transduction if the
      extracellular pH was returned to the mildly acidic state. However, in a minor
      population of cells (40%), the internalized OGR1s were retained in endosomes or
      transported to lysosomes and degraded, leading to low efficiency of their
      recycling to the plasma membrane. Thus, the present live-cell monitoring strongly
      suggests that the signal transduction activity of OGR1 is regulated by pH
      dependent internalization and recycling to the plasma membrane.

PMID- 29655916
TI  - A method for optical imaging and monitoring of the excretion of fluorescent
      nanocomposites from the body using artificial neural networks.
AB  - In this study, a new approach to the implementation of optical imaging of
      fluorescent nanoparticles in a biological medium using artificial neural networks
      is proposed. The studies were carried out using new synthesized nanocomposites -
      nanometer graphene oxides, covered by the poly(ethylene imine)-poly(ethylene
      glycol) copolymer and by the folic acid. We present an example of a successful
      solution of the problem of monitoring the removal of nanocomposites based on nGO
      and their components with urine using fluorescent spectroscopy and artificial
      neural networks. However, the proposed method is applicable for optical imaging
      of any fluorescent nanoparticles used as theranostic agents in biological tissue.

PMID- 29655917
TI  - Ciprofloxacin resistance in nontypable Haemophilus influenzae clinical isolates.

PMID- 29655918
TI  - Embracing Community Ecology in Plant Microbiome Research.
AB  - Community assembly is mediated by selection, dispersal, drift, and speciation.
      Environmental selection is mostly used to date to explain patterns in plant
      microbiome assembly, whereas the influence of the other processes remains largely
      elusive. Recent studies highlight that adopting community ecology concepts
      provides a mechanistic framework for plant microbiome research.

PMID- 29655919
TI  - Endocannabinoid system in systemic lupus erythematosus: First evidence for a
      deranged 2-arachidonoylglycerol metabolism.
AB  - The endocannabinoid (eCB) system plays a key role in many physiological and
      pathological conditions and its dysregulation has been described in several
      rheumatological and autoimmune diseases. Yet, its possible alteration in systemic
      lupus erythematosus (SLE) has never been investigated. Here, we aimed filling
      this gap in plasma and peripheral blood mononuclear cells (PBMCs) of patients
      with SLE and age- and sex- matched healthy subjects (HS). Liquid chromatography
      mass spectrometry quantitation of eCB levels highlighted that plasma levels of 2
      arachidonoylglycerol (2-AG) were significantly increased in SLE patients compared
      to HS (p = 0.0059), and among SLE patients, highest 2-AG levels were associated
      with a lower disease activity. No differences were found in N
      arachidonoylethanolamine (AEA) and its congeners N-palmitoylethanolamine (PEA)
      and N-oleoylethanolamine (OEA) concentrations between the two groups. Moreover,
      gene expression analysis of metabolic enzymes and receptor targets of eCBs and
      investigation of functional activity and protein expression of selected
      components of eCB system disclosed a deranged 2-AG metabolism in patients with
      SLE. Indeed, expression and functional activity of 2-AG biosynthetic enzyme DAGL
      were selectively enhanced in PBMCs of SLE patients compared to HS. In conclusion,
      our results demonstrate, for the first time, an alteration of eCB system in SLE
      patients. They represents the first step toward the understanding of the role of
      eCB system in SLE that likely suggest DAGL and 2-AG as potential biomarkers of
      SLE in easily accessible blood samples. Our data provides proof-of-concept to the
      development of cannabis-based medicine as immune-modulating agents.

PMID- 29655920
TI  - Suppressing Ku70/Ku80 expression elevates homology-directed repair efficiency in
      primary fibroblasts.
AB  - The main DNA repair pathways, nonhomologous end joining (NHEJ) and homology
      directed repair (HDR), are complementary to each other; hence, interruptions of
      the NHEJ pathway can favor HDR. Improving HDR efficiency in animal primary
      fibroblasts can facilitate the generation of gene knock-in animals with
      agricultural and biomedical values by somatic cell nuclear transfer. In this
      study, we used siRNA to suppress the expression of Ku70 and Ku80, which are the
      key factors in NHEJ pathway, to investigate the effect of Ku silencing on the HDR
      efficiency in pig fetal fibroblasts. Down-regulation of Ku70 and Ku80 resulted in
      the promotion of the frequencies of multiple HDR pathways, including homologous
      recombination, single strand annealing, and single-stranded oligonucleotide
      mediated DNA repair. We further evaluated the effects of Ku70 and Ku80 silencing
      on promoting HR-mediated knock-in efficiency in two porcine endogenous genes and
      found a significant increase in the amount of knock-in cells in Ku-silenced
      fibroblasts compared with control. The RNA interference strategy will benefit the
      generation of cell lines and organisms with precise genetic modifications.

PMID- 29655921
TI  - EFOMP policy statement 16: The role and competences of medical physicists and
      medical physics experts under 2013/59/EURATOM.
AB  - On 5 December 2013 the European Council promulgated Directive 2013/59/EURATOM.
      This Directive is important for Medical Physicists and Medical Physics Experts as
      it puts the profession on solid foundations and describes it more
      comprehensively. Much commentary regarding the role and competences has been
      developed in the context of the European Commission project "European Guidelines
      on the Medical Physics Expert" published as Radiation Protection Report RP174.
      The guidelines elaborate on the role and responsibilities under 2013/59/EURATOM
      in terms of a mission statement and competence profile in the specialty areas of
      Medical Physics relating to medical radiological services, namely Diagnostic and
      Interventional Radiology, Radiation Oncology and Nuclear Medicine. The present
      policy statement summarises the provisions of Directive 2013/59/EURATOM regarding
      the role and competences, reiterates the results of the European Guidelines on
      the Medical Physics Expert document relating to role and competences of the
      profession and provides additional commentary regarding further issues arising
      following the publication of the RP174 guidelines.

PMID- 29655922
TI  - Hydrometallurgical recovery of metals: Ce, La, Co, Fe, Mn, Ni and Zn from the
      stream of used Ni-MH cells.
AB  - The utilization of the stream of waste secondary nickel-metal hydride (Ni-MH) and
      lithium-ion (Li-ion) cells, representing annually about 33% of all consumer
      batteries and accumulators placed on the Polish market, will soon become a big
      challenge for both legislators and plants dealing with the recycling of this type
      of hazardous waste. It is due to the fact that no company in Poland operating on
      the market has a complete technology for the processing of a full stream of waste
      chemical energy sources produced in this country. Until now, the most commonly
      used techniques of processing this type of waste were pyrometallurgical process.
      In this paper, the quantitative and qualitative characteristics of the stream of
      waste batteries and accumulators collected at separate collection points are
      presented. The results of metal recovery: caesium, lanthanum, cobalt, iron,
      manganese, nickel and zinc from the stream of waste Ni-MH cells, type R6 (AA),
      using hydrometallurgical methods are also offered. The paper demonstrates that
      one-stage leaching at an initial temperature of 25.0  degrees C, with 3 M H2SO4
      and at the solid to liquid ratio of s/l = 1/10, within 75 min, at a mixing speed
      of 500 rpm and in a strongly acidic environment should be adopted as optimal
      parameters for acid leaching of the paramagnetic fraction created after
      mechanical machining of Ni-MH battery, for which the leaching rates of individual
      metals were as follows: Ce - 97.7%, La - 88.7%, Co - 79.4%, Fe - 68.5%, Mn -
      91.9%, Ni - 66.2% and Zn - 100%.

PMID- 29655923
TI  - Effects of the addition of municipal solid waste incineration fly ash on the
      behavior of polychlorinated dibenzo-p-dioxins and furans in the iron ore
      sintering process.
AB  - Raw materials were co-sintered with municipal solid waste incineration (MSWI) fly
      ash through iron ore sintering to promote the safe treatment and utilization of
      MSWI fly ash. To assess the feasibility of this co-sintering method, in this
      study, the effects of the addition of MSWI fly ash on the formation and emission
      of polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs) were estimated via iron
      ore sintering pot experiments. During co-sintering, most of the PCDD/Fs in the
      added MSWI fly ash were decomposed and transformed into PCDD/Fs associated with
      iron sintering, and the concentrations of lower- and mid-chlorinated congeners
      increased. As there was a sufficient chlorine source and the sintering bed
      permeability was decreased by the addition of MSWI fly ash, the PCDD/F
      concentration in the exhaust gas increased. The mass emission of PCDD/Fs
      decreased; however, the emission of toxic PCDD/Fs increased beyond the total
      emissions from the independent MSW incineration and iron ore sintering processes
      due to the transformation of PCDD/F congeners. The co-sintering may be an
      important solution after technological improvements in the flue gas cleaning
      system and PCDD/F formation inhibition procedures.

PMID- 29655924
TI  - Quantifying household waste of fresh fruit and vegetables in the EU.
AB  - According to national studies conducted in EU countries, fresh fruit and
      vegetables contribute to almost 50% of the food waste generated by households.
      This study presents an estimation of this waste flow, differentiating between
      unavoidable and avoidable waste. The calculation of these two flows serves
      different purposes. The first (21.1 kg per person per year) provides a measure of
      the amount of household waste intrinsically linked to the consumption of fresh
      fruit and vegetables, and which would still be generated even in a zero-avoidable
      waste future scenario. The second (14.2 kg per person per year) is a quantity
      that could be reduced/minimised by applying targeted prevention strategies. The
      unavoidable waste was assessed at product level, by considering the inedible
      fraction and the purchased amounts of the fifty-one most consumed fruits and
      vegetables in Europe. The avoidable waste was estimated at commodity group level,
      based on the results of national studies conducted in six EU member states.
      Significant differences in the amounts of avoidable and unavoidable waste
      generated were found across countries, due to different levels of wasteful
      behaviours (linked to cultural and economic factors) and different consumption
      patterns (influencing the amount of unavoidable waste generated). The results of
      this study have implications for policies both on the prevention and the
      management of household food waste.

PMID- 29655925
TI  - Translation of Public Health Theory into Nursing Practice: Optimization of a
      Nurse-Driven HIV Testing Program in the Emergency Department.

PMID- 29655926
TI  - The Benefits of Introducing the Use of Nitrous Oxide in the Pediatric Emergency
      Department for Painful Procedures.

PMID- 29655927
TI  - Interruptions Experienced by Emergency Nurses: Implications for Subjective and
      Objective Measures of Workload.
AB  - INTRODUCTION: This study aimed to describe interruptions experienced by emergency
      nurses and establish convergence validity of 1 objective workload measure by
      linking interruption characteristics to objective and subjective measures of
      workload. METHODS: Interruptions were captured in real time across 8- or 12-hour
      shifts using a previously validated Workflow Interruptions Tool (WIT). Data
      collected on each interruption included type, priority, and location where the
      interruption occurred. At mid- and end-shift, the Surgery Task Load Index (SURG
      TLX) and the Rapid Cognitive Assessment Tool (RCAT) were administered to
      participating nurses to measure workload subjectively and objectively. RESULTS:
      Thirty-eight emergency nurse shifts were observed. A total of 3,229 interruptions
      were recorded across 372.5 clinical hours and 38 shifts (means [M] = 85.0
      interruptions per shift, standard deviation [SD] = 34.9; M = 8.7 interruptions
      per hour, SD = 3.36). The median duration per interruption was 13.0 seconds. A
      moderate positive association was identified between the number of interruptions
      experienced during a shift and the increased overall SURG-TLX workload reported
      at end-shift, r(36) = 0.323, P = 0.048. Also, a moderate positive association was
      identified between increased reaction times during the RCAT task and increased
      mental demand experienced at end of shift, r(36) = 0.460, P < 0.001. DISCUSSION:
      This study observed interruptions throughout the entirety of a nursing shift and
      found that the majority of interruptions caused by the environment were low
      priority. Targeting interventions to reduce low-priority and environmental
      interruptions may aid in alleviating the impact of interruptions on clinical
      staff and patient care. Furthermore, results demonstrate that the frequency of
      interruptions was perceived to increase the nursing staff workload overall.

PMID- 29655929
TI  - Aging impairs mitochondrial respiratory capacity in classical monocytes.
AB  - Aging is a critical healthcare concern, with age-related inflammation disposing
      individuals to a variety of diseases. Monocytes are affected by the aging
      process, with increased inflammation and impaired cellular functions such as
      phagocytosis. Mechanisms by which aging alters monocyte function are unknown, but
      recent research suggests that the balance of metabolic processes determine immune
      cell phenotype and function. Given the known association between aging and
      mitochondrial dysfunction in other tissues, we hypothesized that aging would
      impair mitochondrial function in monocytes. To test this, we isolated classical
      monocytes from young and older adults and tested mitochondrial function by a
      Seahorse assay. Aging reduced mitochondrial respiratory capacity and spare
      capacity in monocytes. Mitochondrial dysfunction is a potential mechanism by
      which aging alters monocyte phenotype and may impair inflammatory functions,
      especially in low-glucose environments where oxidative metabolism is necessary to
      meet energy demands.

PMID- 29655928
TI  - Effects of 3-months sitting callisthenic balance and resistance exercise on
      aerobic capacity, aortic stiffness and body composition in healthy older
      participants. Randomized Controlled Trial.
AB  - BACKGROUND: Arterial stiffness (AS) is a reduction in the ability of large
      arteries to readily accommodate the increase in blood ejected from the heart
      during systole related with aging. Physical exercise is associated with AS
      reduction. However, it remains controversial as to which modality and intensity
      (resistance vs aerobic, high vs low) would be the most effective. The aim of
      these studies is to examine the effects of 3-months sitting callisthenic balance
      (SCB) and resistance exercise (RET) on aerobic capacity, aortic stiffness and
      body composition in older participants. MATERIAL AND METHODS: Aortic pulse wave
      velocity (PWVao), return time (RT), diastolic reflection area (DRA) and blood
      pressure (BP) level changes were measured with Arteriograph. Aerobic capacity was
      examined with 6-min walk test (6-MWT) and spiroergometry (VO2max). Body
      composition was analyzed by Bioelectric Impedance Analysis using Tanita. RESULTS:
      Significant improvements of BP, PWVao, RT and DRA were observed in the SCB group
      (p = 0.018, p = 0.017 and p = 0.012, respectively). % of fat mass improved in RET
      and SCB group (p = 0.003, p = 0.012, respectively). Visceral fat significantly
      improved in SCB group (p = 0.03). CONCLUSIONS: Despite no significant changes in
      indicators of aerobic capacity (VO2max and 6MWT result) in both groups,
      significant improvement in all measures of AS, except SBPao were observed in the
      SCB group, while no AS improvement in the RET group was noted. There were some
      differences in pattern of body compositions improvement between two groups.

PMID- 29655930
TI  - Circadian signaling in Homarus americanus: Region-specific de novo assembled
      transcriptomes show that both the brain and eyestalk ganglia possess the
      molecular components of a putative clock system.
AB  - Essentially all organisms exhibit recurring patterns of physiology/behavior that
      oscillate with a period of ~24-h and are synchronized to the solar day.
      Crustaceans are no exception, with robust circadian rhythms having been
      documented in many members of this arthropod subphylum. However, little is known
      about the molecular underpinnings of their circadian rhythmicity. Moreover, the
      location of the crustacean central clock has not been firmly established,
      although both the brain and eyestalk ganglia have been hypothesized as loci. The
      American lobster, Homarus americanus, is known to exhibit multiple circadian
      rhythms, and immunodetection data suggest that its central clock is located
      within the eyestalk ganglia rather than in the brain. Here, brain- and eyestalk
      ganglia-specific transcriptomes were generated and used to assess the
      presence/absence of transcripts encoding the commonly recognized protein
      components of arthropod circadian signaling systems in these two regions of the
      lobster central nervous system. Transcripts encoding putative homologs of the
      core clock proteins clock, cryptochrome 2, cycle, period and timeless were found
      in both the brain and eyestalk ganglia assemblies, as were transcripts encoding
      similar complements of putative clock-associated, clock input pathway and clock
      output pathway proteins. The presence and identity of transcripts encoding core
      clock proteins in both regions were confirmed using PCR. These findings suggest
      that both the brain and eyestalk ganglia possess all of the molecular components
      needed for the establishment of a circadian signaling system. Whether the brain
      and eyestalk clocks are independent of one another or represent a single
      timekeeping system remains to be determined. Interestingly, while most of the
      proteins deduced from the identified transcripts are shared by both the brain and
      eyestalk ganglia, assembly-specific isoforms were also identified, e.g., several
      period variants, suggesting the possibility of region-specific variation in clock
      function, especially if the brain and eyestalk clocks represent independent
      oscillators.

PMID- 29655931
TI  - Successful anesthetic management of limb artery thrombectomy by posterior QL
      block in conjunction with FNB.

PMID- 29655932
TI  - Outcome Measurement in the Treatment of Spasmodic Dysphonia: A Systematic Review
      of the Literature.
AB  - PURPOSE: The aim of this review was to systematically identify all available
      studies reporting outcomes measures to assess treatment outcomes for people with
      spasmodic dysphonia (SD). METHODS: Full-text journal articles were identified
      through searches of PubMed, Embase, CINAHL, and Cochrane databases and hand
      searching of journals. RESULTS: A total of 4,714 articles were retrieved from
      searching databases; 1,165 were duplicates. Titles and abstracts of 3,549 were
      screened, with 171 being selected for full-text review. During full-text review,
      101 articles were deemed suitable for inclusion. An additional 24 articles were
      identified as suitable for inclusion through a hand search of reference lists.
      Data were extracted from 125 studies. A total of 220 outcome measures were
      identified. Considered in reference to the World Health Organization
      International Classification of Functioning, Disability and Health (ICF), the
      majority of outcomes were measured at a Body Function level (n = 212, 96%).
      Outcomes that explored communication and participation in everyday life and
      attitudes toward communication (ie, activity and participation domains) were
      infrequent (n = 8; 4%). Quality of life, a construct not measured within the ICF,
      was also captured by four outcome measures. No instruments evaluating
      communication partners' perspectives or burden/disability were identified.
      CONCLUSIONS: The outcome measures used in SD treatment studies are many and
      varied. The outcome measures identified predominately measure constructs within
      the Body Functions component of the ICF. In order to facilitate data synthesis
      across trials, the development of a core outcome set is recommended.

PMID- 29655933
TI  - [Document management systems to support quality management systems at university
      hospitals - an interview-based study].
AB  - In order to save and control the processes and quality of medical services, a
      suitable steering system of all relevant documents is essential from the point of
      view of clinical quality management. Systems supporting an automated steering
      system of documents are called document management systems (DMS), and they also
      enter the healthcare sector. The use of DMS in the German healthcare sector has
      hardly been investigated so far. To close this knowledge gap, interviews were
      carried out with German university hospitals over a six-month period and
      subjected to a qualitative content analysis according to Mayring. In total, 25
      university hospitals agreed to participate in this study, 19 of which have been
      working with a digital DMS for about six years on average. There was a great
      variety among the IT systems used. Document management and usability of the DMS
      as well as its integration into existing IT structures were key decision-making
      criteria for the selection of a digital DMS. In general, the long-term usability
      of the DMS is supported by regular evaluation of one's own requirements for the
      system, administration and training programs. In addition, DMS have a positive
      effect on patient safety and the quality of medical care.

PMID- 29655934
TI  - Age difference between heterosexual partners in Britain: Implications for the
      spread of Chlamydia trachomatis.
AB  - Heterosexual partners often differ in age. Integrating realistic patterns of
      sexual mixing by age into dynamic transmission models has been challenging. The
      effects of these patterns on the transmission of sexually transmitted infections
      (STI) including Chlamydia trachomatis (chlamydia), the most common bacterial STI
      are not well understood. We describe age mixing between new heterosexual partners
      using age- and sex-specific data about sexual behavior reported by people aged 16
      63 years in the 2000 and 2010 British National Surveys of Sexual Attitudes and
      Lifestyles. We incorporate mixing patterns into a compartmental transmission
      model fitted to age- and sex-specific, chlamydia positivity from the same
      surveys, to investigate C. trachomatis transmission. We show that distributions
      of ages of new sex partners reported by women and by men in Britain are not
      consistent with each other. After balancing these distributions, new heterosexual
      partnerships tend to involve men who are older than women (median age difference
      2, IQR -1, 5 years). We identified the most likely age combinations of
      heterosexual partners where incident C. trachomatis infections are generated. The
      model results show that in >50% of chlamydia transmitting partnerships, at least
      one partner is >=25 years old. This study illustrates how sexual behavior data
      can be used to reconstruct detailed sexual mixing patterns by age, and how these
      patterns can be integrated into dynamic transmission models. The proposed
      framework can be extended to study the effects of age-dependent transmission on
      incidence in any STI.

PMID- 29655935
TI  - Establishing the diagnosis of chronic colonization with Pseudomonas aeruginosa of
      cystic fibrosis patients: Comparison of the European consensus criteria with
      genotyping of P. aeruginosa isolates.
AB  - : After antibiotic eradication treatment for a first ever Pseudomonas aeruginosa
      isolation, the European consensus criteria (ECC) are widely used to assess
      colonization status with P. aeruginosa in CF-patients. We evaluated to what
      extent genotyping (GT) of subsequent P. aeruginosa isolates could predict/assess
      chronic colonization (CC), in comparison with the ECC. METHODS: Over a 14-year
      period, sputa were cultured from 80 CF-patients (age range: 2-51 years), from a
      first ever isolation of P. aeruginosa onwards. Patients with a positive culture
      for P. aeruginosa received antibiotic eradication treatment. For the 40 patients
      for whom three or more P. aeruginosa isolates were available, these isolates were
      genotyped. RESULTS: According to the ECC, 27 out of the 40 patients (67.5%)
      became CC during the study period (ECC-positive patients). Genotyping confirmed
      persistence of the same genotype for 25 of these ECC-positive patients.
      Genotyping indicated persistence of the same genotype for at least two subsequent
      isolates for 5 out of 13 ECC-negative patients. Culture-positivity
      characteristics of the 27 ECC-positive patients corresponded well to those of the
      30 GT-positive patients, with an overall higher number of positive cultures as
      well as a shorter interval in between first and second isolate compared to ECC
      negative and GT-negative patients. Genotyping indicated persistence of the same
      genotype on average 9.3 months earlier than CC according to the ECC (P < 0.01).
      CONCLUSIONS: Genotyping of P. aeruginosa isolates confirmed CC for 25 out of 27
      ECC-positive patients (92.6% specificity) and predicted CC 9.3 months earlier
      than the ECC.

PMID- 29655937
TI  - The left inferior frontal gyrus: A neural crossroads between abstract and
      concrete knowledge.
AB  - Evidence from both neuropsychology and neuroimaging suggests that different types
      of information are necessary for representing and processing concrete and
      abstract word meanings. Both abstract and concrete concepts, however, conjointly
      rely on perceptual, verbal and contextual knowledge, with abstract concepts
      characterized by low values of imageability (IMG) (low sensory-motor grounding)
      and low context availability (CA) (more difficult to contextualize). Imaging
      studies supporting differences between abstract and concrete concepts show a
      greater recruitment of the left inferior frontal gyrus (LIFG) for abstract
      concepts, which has been attributed either to the representation of abstract
      specific semantic knowledge or to the request for more executive control than in
      the case of concrete concepts. We conducted an fMRI study on 27 participants,
      using a lexical decision task involving both abstract and concrete words, whose
      IMG and CA values were explicitly modelled in separate parametric analyses. The
      LIFG was significantly more activated for abstract than for concrete words, and a
      conjunction analysis showed a common activation for words with low IMG or low CA
      only in the LIFG, in the same area reported for abstract words. A regional
      template map of brain activations was then traced for words with low IMG or low
      CA, and BOLD regional time-series were extracted and correlated with the specific
      LIFG neural activity elicited for abstract words. The regions associated to low
      IMG, which were functionally correlated with LIFG, were mainly in the left
      hemisphere, while those associated with low CA were in the right hemisphere.
      Finally, in order to reveal which LIFG-related network increased its connectivity
      with decreases of IMG or CA, we conducted generalized psychophysiological
      interaction analyses. The connectivity strength values extracted from each region
      connected with the LIFG were correlated with specific LIFG neural activity for
      abstract words, and a regression analysis was conducted to highlight which areas
      recruited by low IMG or low CA predicted the greater activation of the IFG for
      abstract concepts. Only the left middle temporal gyrus/angular gyrus, known to be
      involved in semantic processing, was a significant predictor of LIFG activity
      differentiating abstract from concrete words. The results show that the abstract
      conceptual processing requires the interplay of multiple brain regions, necessary
      for both the intrinsic and extrinsic properties of abstract knowledge. The LIFG
      can be thus identified as the neural crossroads between different types of
      information equally necessary for representing processing and differentiating
      abstract concepts from concrete ones.

PMID- 29655936
TI  - Dynamic causal modelling on infant fNIRS data: A validation study on a
      simultaneously recorded fNIRS-fMRI dataset.
AB  - Tracking the connectivity of the developing brain from infancy through childhood
      is an area of increasing research interest, and fNIRS provides an ideal method
      for studying the infant brain as it is compact, safe and robust to motion.
      However, data analysis methods for fNIRS are still underdeveloped compared to
      those available for fMRI. Dynamic causal modelling (DCM) is an advanced
      connectivity technique developed for fMRI data, that aims to estimate the
      coupling between brain regions and how this might be modulated by changes in
      experimental conditions. DCM has recently been applied to adult fNIRS, but not to
      infants. The present paper provides a proof-of-principle for the application of
      this method to infant fNIRS data and a demonstration of the robustness of this
      method using a simultaneously recorded fMRI-fNIRS single case study, thereby
      allowing the use of this technique in future infant studies. fMRI and fNIRS were
      simultaneously recorded from a 6-month-old sleeping infant, who was presented
      with auditory stimuli in a block design. Both fMRI and fNIRS data were
      preprocessed using SPM, and analysed using a general linear model approach. The
      main challenges that adapting DCM for fNIRS infant data posed included: (i) the
      import of the structural image of the participant for spatial pre-processing,
      (ii) the spatial registration of the optodes on the structural image of the
      infant, (iii) calculation of an accurate 3-layer segmentation of the structural
      image, (iv) creation of a high-density mesh as well as (v) the estimation of the
      NIRS optical sensitivity functions. To assess our results, we compared the values
      obtained for variational Free Energy (F), Bayesian Model Selection (BMS) and
      Bayesian Model Average (BMA) with the same set of possible models applied to both
      the fMRI and fNIRS datasets. We found high correspondence in F, BMS, and BMA
      between fMRI and fNIRS data, therefore showing for the first time high
      reliability of DCM applied to infant fNIRS data. This work opens new avenues for
      future research on effective connectivity in infancy by contributing a data
      analysis pipeline and guidance for applying DCM to infant fNIRS data.

PMID- 29655939
TI  - Improving the signal detection accuracy of functional Magnetic Resonance Imaging.
AB  - A major drawback of functional Magnetic Resonance Imaging (fMRI) concerns the
      lack of detection accuracy of the measured signal. Although this limitation stems
      in part from the neuro-vascular nature of the fMRI signal, it also reflects
      particular methodological decisions in the fMRI data analysis pathway. Here we
      show that the signal detection accuracy of fMRI is affected by the specific way
      in which whole-brain volumes are created from individually acquired brain slices,
      and by the method of statistically extracting signals from the sampled data. To
      address these limitations, we propose a new framework for fMRI data analysis. The
      new framework creates whole-brain volumes from individual brain slices that are
      all acquired at the same point in time relative to a presented stimulus. These
      whole-brain volumes contain minimal temporal distortions, and are available at a
      high temporal resolution. In addition, statistical signal extraction occurred on
      the basis of a non-standard time point-by-time point approach. We evaluated the
      detection accuracy of the extracted signal in the standard and new framework with
      simulated and real-world fMRI data. The new slice-based data-analytic framework
      yields greatly improved signal detection accuracy of fMRI signals.

PMID- 29655940
TI  - Audio-visual speech processing in age-related hearing loss: Stronger integration
      and increased frontal lobe recruitment.
AB  - Hearing loss is associated with difficulties in understanding speech, especially
      under adverse listening conditions. In these situations, seeing the speaker
      improves speech intelligibility in hearing-impaired participants. On the neuronal
      level, previous research has shown cross-modal plastic reorganization in the
      auditory cortex following hearing loss leading to altered processing of auditory,
      visual and audio-visual information. However, how reduced auditory input effects
      audio-visual speech perception in hearing-impaired subjects is largely unknown.
      We here investigated the impact of mild to moderate age-related hearing loss on
      processing audio-visual speech using functional magnetic resonance imaging.
      Normal-hearing and hearing-impaired participants performed two audio-visual
      speech integration tasks: a sentence detection task inside the scanner and the
      McGurk illusion outside the scanner. Both tasks consisted of congruent and
      incongruent audio-visual conditions, as well as auditory-only and visual-only
      conditions. We found a significantly stronger McGurk illusion in the hearing
      impaired participants, which indicates stronger audio-visual integration.
      Neurally, hearing loss was associated with an increased recruitment of frontal
      brain areas when processing incongruent audio-visual, auditory and also visual
      speech stimuli, which may reflect the increased effort to perform the task.
      Hearing loss modulated both the audio-visual integration strength measured with
      the McGurk illusion and brain activation in frontal areas in the sentence task,
      showing stronger integration and higher brain activation with increasing hearing
      loss. Incongruent compared to congruent audio-visual speech revealed an opposite
      brain activation pattern in left ventral postcentral gyrus in both groups, with
      higher activation in hearing-impaired participants in the incongruent condition.
      Our results indicate that already mild to moderate hearing loss impacts audio
      visual speech processing accompanied by changes in brain activation particularly
      involving frontal areas. These changes are modulated by the extent of hearing
      loss.

PMID- 29655941
TI  - Abuse and disrespect in childbirth assistance in Italy: A community-based survey.

PMID- 29655938
TI  - Delineation of early brain development from fetuses to infants with diffusion MRI
      and beyond.
AB  - Dynamic macrostructural and microstructural changes take place from the mid-fetal
      stage to 2 years after birth. Delineating structural changes of the brain during
      early development provides new insights into the complicated processes of both
      typical development and the pathological mechanisms underlying various
      psychiatric and neurological disorders including autism, attention deficit
      hyperactivity disorder and schizophrenia. Decades of histological studies have
      identified strong spatial and functional maturation gradients in human brain gray
      and white matter. The recent improvements in magnetic resonance imaging (MRI)
      techniques, especially diffusion MRI (dMRI), relaxometry imaging, and
      magnetization transfer imaging (MTI) have provided unprecedented opportunities to
      non-invasively quantify and map the early developmental changes at whole brain
      and regional levels. Here, we review the recent advances in understanding early
      brain structural development during the second half of gestation and the first
      two postnatal years using modern MR techniques. Specifically, we review studies
      that delineate the emergence and microstructural maturation of white matter
      tracts, as well as dynamic mapping of inhomogeneous cortical microstructural
      organization unique to fetuses and infants. These imaging studies converge into
      maturational curves of MRI measurements that are distinctive across different
      white matter tracts and cortical regions. Furthermore, contemporary models
      offering biophysical interpretations of the dMRI-derived measurements are
      illustrated to infer the underlying microstructural changes. Collectively, this
      review summarizes findings that contribute to charting spatiotemporally
      heterogeneous gray and white matter structural development, offering MRI-based
      biomarkers of typical brain development and setting the stage for understanding
      aberrant brain development in neurodevelopmental disorders.

PMID- 29655942
TI  - PINK1 p.K520RfsX3 mutation identified in a Chinese family with early-onset
      Parkinson's disease.
AB  - Parkinson's disease (PD) features selective loss of dopaminergic neurons of the
      substantia nigra pars compacta accompanied by the accumulation and aggregation of
      alpha-synuclein in Lewy bodies. PTEN induced putative kinase 1 gene (PINK1)
      mutations are the second most common genetic cause of autosomal recessive early
      onset Parkinson's disease (EOPD). A single nucleotide deletion in PINK1 exon 8
      (c.1557delG) was identified in a consanguineous Chinese family with EOPD. The
      homozygous deletion was co-segregated with disease in the family and resulted in
      a frameshift after codon 520 with a premature termination at codon 522
      (p.K520RfsX3). These findings have significant implications on genetic counseling
      for the family and may be helpful in considering potential pathogenesis-targeted
      and disease-modifying strategies which should further improve patient quality of
      life.

PMID- 29655943
TI  - Effects of a histamine H4 receptor antagonist on cisplatin-induced anorexia in
      mice.
AB  - Cancer chemotherapy often induces gastrointestinal symptoms such as anorexia,
      nausea, and vomiting. Antiemetic agents are effective in inhibiting nausea and
      vomiting, but patients still experience anorexia. We previously reported that
      chemotherapeutic agent-induced anorexia is associated with an increase of
      inflammatory cytokines. Other studies also reported that antagonism of the
      histamine H4 receptor is anti-inflammatory. In this study, we investigated the
      involvement of the H4 receptor in the development of chemotherapy-induced
      anorexia in mice. Cisplatin-induced anorexia occurred within 24 h of its
      administration and continued for 3 days. The early phase (day 1), but not the
      delayed phase (days 2 and 3), of anorexia was inhibited by the daily injection of
      a 5-HT3 receptor antagonist (granisetron). However, a corticosteroid
      (dexamethasone) or selective H4 receptor antagonist (JNJ7777120) abolished the
      delayed phases of anorexia. Cisplatin significantly increased TNF-alpha mRNA
      expression in the hypothalamus and spleen, and the period of expression increase
      paralleled the onset period of anorexia. In addition, pretreatment with
      JNJ7777120 completely inhibited the increased expression. These results suggest
      that TNF-alpha mRNA expression via H4 receptors may contribute to the development
      of cisplatin-induced anorexia, and that H4 receptor antagonists are potentially
      useful treatments.

PMID- 29655944
TI  - Regular aerobic exercise correlates with reduced anxiety and incresed levels of
      irisin in brain and white adipose tissue.
AB  - We have recently shown that regular voluntary aerobic exercised rats have low
      levels of anxiety. Irisin is an exercise-induced myokine that is produced by many
      tissues; and the role it plays in anxiolytic behavior is unknown. In this study
      we aimed to investigate the correlation between anxiety like behavior and irisin
      levels following regular voluntary aerobic exercise in male mice. We've have
      shown that anxiety levels decreased in exercised mice, while irisin levels
      increased in the brain, brown adipose tissue, white adipose tissue, kidney, and
      pancreas tissues. No significant difference of irisin levels in the liver, muscle
      and serum were detected in the exercise group, when compared to controls. In
      addition, there was a strong positive correlation between brain irisin levels and
      activity in middle area of open field test and in the open arms of elevated plus
      maze test; both which are indicators of low anxiety levels. Our results suggest
      that decrease in anxiolytic behavior due to regular voluntary exercise may be
      associated with locally produced brain irisin. White adipose tissue irisin levels
      also correlated very strongly with low anxiety. However, no serum irisin increase
      was detected, ruling out the possibility of increased peripheral irisin levels
      affecting the brain via the bloodstream. Further research is necessary to explain
      the mechanisms of which peripheral and central irisin effects anxiety and the
      brain region affected.

PMID- 29655945
TI  - Long term Westernized diet leads to region-specific changes in brain signaling
      mechanisms.
AB  - Western diets, high in fat and energy, are associated with cognitive deficits in
      humans and animal models, but the underlying mechanisms are not fully elucidated.
      This includes whether diet-induced dyslipidemia per se negatively impacts brain
      signaling. Here we investigate the effects of dyslipidemia induced by two high
      fat diets with or without high sucrose on hippocampal and frontal cortical
      oxidative stress, brain-derived neurotrophic factor (BDNF) and down-stream
      markers of synaptic plasticity, as well as alterations in monoaminergic
      neurotransmitter levels. A high fat diet was associated with decreased
      antioxidant status (vitamin C), increased serotonin in the frontal cortex, and
      increased ratio of phosphorylated Ca2+/calmodulin-dependent protein kinase II in
      the hippocampus, while a high fat and sucrose diet decreased levels of vitamin C
      in the frontal cortex and BDNF in the hippocampus. Markers of dyslipidemia
      correlated significantly with cerebral vitamin C levels, monoaminergic
      neurotransmitters and metabolites in the frontal cortex, but not in the
      hippocampus. Thus, a high fat diet caused regional alterations in antioxidant
      levels, neurochemistry and molecular markers in the non-obese dyslipidemic guinea
      pig.

PMID- 29655946
TI  - Big data handling mechanisms in the healthcare applications: A comprehensive and
      systematic literature review.
AB  - Healthcare provides many services such as diagnosing, treatment, prevention of
      diseases, illnesses, injuries, and other physical and mental disorders. Large
      scale distributed data processing applications in healthcare as a basic concept
      operates on large amounts of data. Therefore, big data application functions are
      the main part of healthcare operations, but there was not any comprehensive and
      systematic survey about studying and evaluating the important techniques in this
      field. Therefore, this paper aims at providing the comprehensive, detailed, and
      systematic study of the state-of-the-art mechanisms in the big data related to
      healthcare applications in five categories, including machine learning, cloud
      based, heuristic-based, agent-based, and hybrid mechanisms. Also, this paper
      displayed a systematic literature review (SLR) of the big data applications in
      the healthcare literature up to the end of 2016. Initially, 205 papers were
      identified, but a paper selection process reduced the number of papers to 29
      important studies.

PMID- 29655947
TI  - Co-occurrence of medical conditions: Exposing patterns through probabilistic
      topic modeling of snomed codes.
AB  - Patients associated with multiple co-occurring health conditions often face
      aggravated complications and less favorable outcomes. Co-occurring conditions are
      especially prevalent among individuals suffering from kidney disease, an
      increasingly widespread condition affecting 13% of the general population in the
      US. This study aims to identify and characterize patterns of co-occurring medical
      conditions in patients employing a probabilistic framework. Specifically, we
      apply topic modeling in a non-traditional way to find associations across SNOMED
      CT codes assigned and recorded in the EHRs of >13,000 patients diagnosed with
      kidney disease. Unlike most prior work on topic modeling, we apply the method to
      codes rather than to natural language. Moreover, we quantitatively evaluate the
      topics, assessing their tightness and distinctiveness, and also assess the
      medical validity of our results. Our experiments show that each topic is
      succinctly characterized by a few highly probable and unique disease codes,
      indicating that the topics are tight. Furthermore, inter-topic distance between
      each pair of topics is typically high, illustrating distinctiveness. Last, most
      coded conditions grouped together within a topic, are indeed reported to co-occur
      in the medical literature. Notably, our results uncover a few indirect
      associations among conditions that have hitherto not been reported as correlated
      in the medical literature.

PMID- 29655948
TI  - Outcome of catheter ablation for ventricular tachycardia in patients with
      ischemic cardiomyopathy: A systematic review and meta-analysis of randomized
      clinical trials.
AB  - BACKGROUND: Current ventricular tachycardia (VT) management in patients with
      ischemic cardiomyopathy (ICM) includes optimal medical therapy, ICDs device
      therapy, and antiarrhythmic medications. Data about outcomes of catheter ablation
      (CA) in these patients is scarce. We aimed to perform a meta-analysis of RCTs to
      compare outcomes of CA vs conventional management of VT in ICM patients who had
      ICD. METHODS: A systematic review and meta-analysis of published RCTs between
      January 1970 and December 2016 were performed. Random effects DerSimonian-Laird
      risk ratios (RR) were calculated. Sensitivity analyses using fixed-effects
      summary odds ratios (OR) were performed using Peto model. Outcomes of interest
      were: all-cause mortality (ACM), cardiovascular death (CVD), CV disease-related
      hospitalization, VT storms, and ICD shocks. RESULTS: 4 RCTs were identified (521
      patients (261 had CA), mean age: 66.4 +/- 1.7 years, 91.5% male, mean follow-up:
      19 months). No difference observed between VT ablation and conventional
      management regarding ACM (RR 0.94, 95% CI, 0.66-1.32, p = 0.70) or CVD (RR 0.82,
      95% CI, 0.52-1.29, p = 0.39). VT ablation was associated with less CV disease
      related hospitalization (RR 0.72, 95% CI, 0.54-0.96, p = 0.02), VT storms (RR
      0.71, 95% CI, 0.52-0.97, p = 0.03), and trend towards reducing ICD shocks (RR
      0.59, 95% CI, 0.34-1.05, p = 0.07). In sensitivity analysis using fixed-effects
      OR, CA was associated with significant reduction in ICD shocks. CONCLUSION: In
      patients with ICM, VT ablation reduced CV disease-related hospitalization, VT
      storms, and ICD shocks when compared to conventional management with no mortality
      benefit over a relatively short mean follow-up period.

PMID- 29655949
TI  - Incidence and predictors of 6 months mortality after an acute heart failure event
      in rural Uganda: The Mbarara Heart Failure Registry (MAHFER).
AB  - OBJECTIVE: We sought to estimate the incidence and predictors of all-cause
      mortality 6 months after heart failure hospitalization in Uganda. METHODS:
      Mbarara Heart Failure Registry is a cohort of patients hospitalized with a
      clinical diagnosis of heart failure at Mbarara Regional Referral Hospital,
      Uganda. We measured serum electrolytes, cardiac markers, and echocardiograms. All
      participants were followed until death or end of 6 months. We used Fine and Gray
      models to estimate the incidence and predictors all-cause mortality. RESULTS: A
      total of 215 participants were enrolled, 141 (66%) were women, and mean age 53
      (standard deviation 22) years. Nineteen (9%) had diabetes, 40 (19%) had HIV, and
      119 (55%) had hypertension. The overall incidence of all-cause mortality was 3.58
      (95% CI 2.92, 4.38) per 1000 person-days. Men had higher incidence of death
      compared to women (4.02 vs 3.37 per 1000 person-days). The incidence of all-cause
      mortality during hospitalization was almost twice that of in the community (27.5
      vs 14.77 per 1000 person-days). In adjusted analysis, increasing age, NYHA class
      IV, decreasing renal function, smoking, each unit increase in serum levels of
      Potassium, BNP, and Creatine kinase-MB predicted increased incidence of 6 months
      all-cause death whereas taking beta-blockers and having an index admission on a
      weekend compared to a week day predicted survival. CONCLUSIONS AND
      INTERPRETATION: There is a high incidence of all-cause mortality occurring in
      hospital among patients hospitalized with heart failure in rural Uganda. Heart
      failure directed therapies should be instituted to curb heart failure-related
      mortality.

PMID- 29655950
TI  - Strengths and weaknesses of echocardiography for the diagnosis of pulmonary
      hypertension.
AB  - Doppler echocardiography is extensively used in clinical practice for the
      screening and detection of pulmonary hypertension (PH). It allows for accurate
      estimates of pulmonary artery pressures, but with moderate precision, which
      explains why it is more appropriate for population studies than for definitive
      diagnosis of PH in individual patients. Moreover, echocardiography allows one to
      distinguish different patterns of right ventricular remodelling in various forms
      of PH and enables clinically satisfactory differentiation between pre- and post
      capillary PH. This article will review the methods for evaluating PH by
      echocardiography, while also providing an insight into specific strengths and
      weaknesses.

PMID- 29655951
TI  - ACEF score adapted to ST-elevation myocardial infarction patients: The ACEF-STEMI
      score.
AB  - BACKGROUND: The age, creatinine and ejection fraction (ACEF) score has originally
      been developed for risk stratification of patients undergoing elective cardiac
      surgery. In patients with stable coronary artery disease treated by percutaneous
      coronary intervention (PCI), the prognostic accuracy of ACEF could be further
      improved by modifying the original scoring system (called "modified ACEF" or
      "ACEF-MDRD"). We aimed to specifically adapt the ACEF score for risk assessment
      of ST-elevation myocardial infarction (STEMI) patients. METHODS: In this
      observational study, 390 STEMI patients undergoing primary PCI were included.
      Clinical endpoint was the occurrence of major adverse cardiovascular events
      (MACE) comprising all-cause mortality, non-fatal re-infarction, stroke and new
      congestive heart failure. RESULTS: Original ACEF (area under the curve (AUC):0.63
      [95%CI:0.53-0.73]; p = 0.01) and ACEF-MDRD score (AUC:0.62 [95%CI:0.53-0.72]; p =
      0.01) significantly but weakly predicted MACE (n = 41, 11%). The addition of
      creatinine > 2 mg/dl (as suggested in original ACEF, p = 0.32) or eGFR steps as
      proposed in ACEF-MDRD (p = 0.17) to age/EF ratio were not associated with net
      reclassification improvements (NRI), but DeltaeGRF (>10 ml/min/1.73 m2 decrease
      within three days after PCI) led to an NRI of 0.29 (95%CI:0.14-0.45; p < 0.001).
      Replacement of cross-sectional renal assessment by DeltaeGRF and addition of 3
      clinical parameters (diabetes, anterior infarct location and C-reactive protein),
      forming the new ACEF-STEMI score, led to a significant improvement in MACE
      prediction (AUC:0.75 [95%CI:0.66-0.84]) as compared to original ACEF or ACEF-MDRD
      (both p = 0.03). CONCLUSIONS: In STEMI patients undergoing primary PCI, the novel
      ACEF-STEMI score provided strong prognostic value and superior discriminative
      ability as compared to the previously described original ACEF or ACEF-MDRD
      scores.

PMID- 29655952
TI  - Population-level incidence and outcomes of myocardial infarction with non
      obstructive coronary arteries (MINOCA): Insights from the Alberta contemporary
      acute coronary syndrome patients invasive treatment strategies (COAPT) study.
AB  - BACKGROUND: Myocardial infarction with non-obstructive coronary arteries (MINOCA)
      is a known clinical conundrum with limited investigation. Using a large
      population-based cohort, we examined the incidence, demographic profile, use of
      evidence-based medicines (EBM) and clinical outcomes of MINOCA patients. METHODS:
      Patients hospitalized with a primary diagnosis of MI who underwent coronary
      angiography between 01/04/2002 and 31/03/2014 in Alberta, Canada, were included
      in the study. Comparisons were made between patients with MINOCA versus
      obstructive coronary disease (OCD). The primary composite endpoint was 1-year all
      cause death or re-MI. RESULTS: Of 35,928 patients hospitalized with MI, 2092
      (5.8%) had MINOCA. In-hospital mortality rate was 0.8% among MINOCA, and 2.7%
      among patients with OCD (p < 0.0001). At 6 months, cardiovascular EBM rates were
      significantly lower among MINOCA patients compared to OCD patients. One-year
      death/re-MI rate was 5.3% in MINOCA and 8.9% in patients with OCD (adjusted
      hazard ratio (AHR) 0.75, 95% confidence interval (CI) 0.62-0.92, p < 0.0001).
      Five-year mortality rates were 10.9% in MINOCA and 16.0% in patients with OCD.
      Upon further stratification, 770 (36.8%) of MINOCA patients had no angiographic
      evidence of CAD (i.e. normal angiograms). EBM rates were even lower among these
      patients. One-year death/re-MI rate among these patients was 3.9% as compared to
      6.1% among MINOCA patients with stenosis <50% (AHR 0.68, 95% CI 0.44-1.07, p =
      0.028). CONCLUSIONS: The population-level incidence of MINOCA is approximately
      5%. Despite their apparently benign anatomic findings, efforts must be made to
      improve secondary prevention strategies to reduce the burden of long-term adverse
      outcomes in this population.

PMID- 29655953
TI  - Risk factors predisposing to acute coronary syndromes in young women <=45 years
      of age.
AB  - BACKGROUND: Acute coronary syndromes (ACS) are rare in young women. The purpose
      of this study was to characterize risk factors (RF) predisposing to ACS in young
      women and evaluate possible age-related differences. METHODS AND RESULTS: We
      studied 1941 young women with ACS aged <=45 years (<=45ACS) from the PL-ACS
      registry and compared them with two control groups: 4275 women aged 63-64 years
      with ACS (63-64ACS) from the PL-ACS registry and 1170 young healthy women aged
      <=45 years (<=45H) without confirmed coronary artery disease (CAD), from two
      national, representative, cross-sectional population health surveys, NATPOL 2011
      and WOBASZ. The prevalence of major RF in these three groups was as follows,
      respectively: (<=45 ACS vs. 63-64ACS vs. <=45H, for all P < 0.0001): hypertension
      49.8% vs. 78.1% vs. 16.8%; hypercholesterolemia 36.1% vs. 44.3% vs. 12.9%;
      obesity 22.3% vs. 28.1% vs. 15.6%; diabetes 10.6% vs. 29.9% vs. 1.8% and smoking
      48.7% vs. 22.2% vs. 39%. Healthy women had the lowest number of major RF (1.7 +/-
      1.2 vs. 2.0 +/- 1.1 vs. 1.1 +/- 1.0). No RF was found in 16.7% vs. 8.2% vs. 34.4%
      women, respectively. Independent predictors of ACS in the <=45ACS group included
      diabetes [odds ratio (OR) 6.66, 95% confidence interval (CI) 3.47-12.74]*,
      hypertension (OR 4.30, 95% CI 3.42-5.38)*, hypercholesterolemia (OR 3.45; 95% CI
      2.60-4.29)*, and smoking (OR 1.63, 95% CI 1.34-1.98)*, *(P < 0.0001 for all).
      CONCLUSIONS: The prevalence of risk factors for acute coronary syndromes in young
      women with ACS is different to those in healthy women and to those in older
      women. The prevalence of smoking was higher. The strongest predictor of ACS in
      women <=45 years of age was diabetes, with a 6-fold increase in risk. There is
      still need to improve the cardio-vascular primary prevention and health promotion
      in the population of young women.

PMID- 29655954
TI  - Corrigendum to "A systematic review of clozapine-induced myocarditis" [Int. J.
      Cardiol. 259(2018) 122-129].

PMID- 29655955
TI  - Employment and paid work among participants in a randomized controlled trial
      comparing diacetylmorphine and hydromorphone.
AB  - BACKGROUND: Employment is one of the less studied but a significant outcome of
      medication-assisted treatment. Thus, we aimed to explore employment outcomes of
      medication-assisted treatment with hydromorphone (HDM) or diacetylmorphine (DAM).
      The secondary aim was to estimate characteristics of this population as well as
      treatment-related factors associated with these outcomes. METHODS: This was a
      secondary analysis of a randomized, double blind controlled trial. A total of 102
      and 100 participants were randomized to receive injectable DAM or HDM for 6
      months respectively. In stage 2, 144 participants were randomized again to
      receive either oral or injectable forms of the medication they received for
      another 6 months. Participants were interviewed at 5 timepoints: before and 3, 6,
      9 and 12 months after treatment assignment. Generalized estimating equations
      (GEE) with a logit link was fitted to determine factors related to paid work in
      the past 30 days. RESULTS: Mean age of participants was 44.3 (SD = 9.6) and 59
      (29.2%) participants were men. At each timepoint, 6-8 (3.6%-4.1%) participants
      reported employment in the past 30 days and 40 to 52 (19.7%-26.7%) reported
      minimum 1 day of paid work. University or college education [OR = 2.12: 95% CI =
      (1.25, 3.62), P = 0.01] was significantly associated with paid work after
      adjustment for age, gender, treatment arms, timepoints, days receiving study
      treatment, physical health, psychological health and crack cocaine use in the
      past 30 days. CONCLUSION: The rate of employment was lower among participants of
      this study compared to similar studies on heroin-assisted treatment. Higher
      education was associated with increased odds of paid work. A large gap exists
      between employment rate and the proportion of participants who reported paid
      work. Supported employment and occupational therapy could optimize the employment
      outcomes of this population.

PMID- 29655956
TI  - Streptococcus agalactiae that caused meningitis in healthy adults in 1998 are
      ST283, the same type that caused a food-borne outbreak of invasive sepsis in
      2015: an observational molecular epidemiology study.

PMID- 29655957
TI  - Ectopic Cushing syndrome: Report of 9 cases.
AB  - INTRODUCTION: Ectopic Cushing's syndrome (ECS) is a rare condition caused by ACTH
      secretion by extrapituitary tumors. Its low frequency makes it difficult to
      acquire experience in its management. The aim of this study was to describe
      patients with ECS seen at the endocrinology department of a tertiary hospital
      over 15 years. METHODS: This was a retrospective study of the clinical,
      biochemical and radiographic data, treatment, and course of patients with ECS
      seen from 2000 to 2015. RESULTS: Nine patients (6 of them female) with a mean age
      of 47 years were included in the study. The clinical syndrome developed in less
      than 3 months in all cases but one, and most patients also had edema,
      hyperpigmentation and/or hypokalemia. Mean urinary free cortisol and ACTH levels
      were 2,840MUg/24h and 204pg/mL respectively. The ectopic origin was confirmed by
      a combination of dynamic non-invasive tests and radiographic studies in most
      cases. The tumor responsible could be identified in 8 cases, and 7 patients had
      metastatic dissemination. Primary treatment was surgery in one patient, surgery
      combined with systemic therapy in 3, and chemotherapy in the other 3 patients.
      Bilateral adrenalectomy was required in 4 patients to control hypercortisolism.
      After a mean follow-up of 40 months, 3 patients died, 5 were still alive, and one
      had been lost to follow-up. CONCLUSIONS: Our study confirms that ECS covers a
      wide spectrum of tumors of different aggressiveness and nature. The ectopic
      origin of Cushing's syndrome can usually, be suspected and confirmed in most
      cases without the need for invasive tests. Control of both hypercortisolism and
      the tumor requires multiple treatment modalities, and multidisciplinary
      management is recommended.

PMID- 29655958
TI  - A second-derivate fitting algorithm for the quantification of free hemoglobin in
      human plasma.
AB  - BACKGROUND: Assessment of hemolysis in vivo is becoming increasingly relevant in
      critical care. Current methods (Harboe, 1959) for quantifying the free hemoglobin
      (fHb) content produce unsatisfactory results in case of hyperbilirubinemia, a
      frequent condition in patients at risk for intravascular hemolysis. METHODS: A
      novel evaluation method based on second-derivative fitting to quantify fHb
      content was developed. The method uses spectrophotometric data from 350 to 650 nm
      recorded with standard instruments as input. To evaluate the power of the new
      method, plasma of patients and non-icteric plasma of healthy volunteers were
      spiked with fHb concentrations up to 2000 mg/L and compared to methods described
      in the literature by Harboe, Noe and Fairbanks. All measurements were done in
      compliance with the bioanalytical method validation protocol from the European
      Medicines Agency. RESULTS: Both the second-derivative fitting algorithm as well
      as the methods of Harboe, Noe and Fairbanks quantified fHb accurately in non
      icteric samples, with inaccuracy and imprecision below 10%. For icteric specimen,
      false high results were obtained with the established formulas for fHb
      concentrations below 700 mg/L. In contrast, no interference was found with the
      second-derivate fitting method for bilirubin concentrations up to 465 MUmol/L.
      The lower limits of quantifications for the second-derivative fitting algorithm
      were specified in agreement with the EMA guideline with 25 mg/L fHb for both non
      icteric and icteric specimens. CONCLUSIONS: A user-friendly, computer-based
      algorithm is reported that allows the accurate quantification of fHb
      concentrations in the presence of high bilirubin concentrations. The new method
      allows for uniform sample preparation with only a single dilution step and can be
      readily implemented in any laboratory on standard spectrophotometers using the
      provided supplementary Microsoft Excel macro.

PMID- 29655959
TI  - The efficient workflow to decrease the manual microscopic examination of urine
      sediment using on-screen review of images.
AB  - BACKGROUND: The manual microscopic examination (MME) of urine sediment is labor
      intensive, time-consuming, and imprecise. Therefore, automated urinalysis systems
      based on flow cytometry or digital imaging techniques could replace MME. The
      purpose of this study was to evaluate the rate of MME using two automated urine
      sediment analyzers, alone and in combination. METHODS: This study was conducted
      using the freshly collected urine specimens of 1055 in-patients and 1119 out
      patients. All samples were analyzed using UF-1000i (Sysmex Corporation) and Cobas
      6500 instrument (Roche Diagnostics International). The rate of MME was evaluated
      using two analyzers, both individually and in combination. RESULTS: Using the UF
      1000i alone, 34.2% and 16.8%, respectively, of in- and out-patient samples were
      analyzed by MME, compared to 15.6% and 3.7%, respectively, using the Cobas 6500.
      In combined assay using the UF-1000i followed by the Cobas 6500, 27.9% and 11.3%
      in-patient samples required on-screen review and MME, respectively. And the
      respective rates were 10.3% and 2.7% of out-patient. Samples using the Cobas 6500
      followed by the UF-1000i, 42.3% and 11.3% in-patient needed on-screen review and
      MME, respectively. And the respective rates were 18.9% and 2.7% of out-patient
      samples. CONCLUSIONS: Use of the Cobas 6500 compared to the UF-1000i resulted in
      decreases in the rate of MME from 34.2% to 15.6% for in-patient samples, and from
      16.8% to 3.7% for out-patient samples. Use of the Cobas 6500 reduced the rate of
      MME, and compared to use of only the Cobas 6500, the combined use resulted in a
      reduction in the rate of on-screen review.

PMID- 29655960
TI  - Systemic redox biomarkers and their relationship to prognostic risk markers in
      autosomal dominant polycystic kidney disease and IgA nephropathy.
AB  - BACKGROUND: Oxidative stress is evident from an early stage in chronic kidney
      disease (CKD). Therefore, we investigated redox biomarkers in polycystic kidney
      disease (ADPKD) and IgA nephropathy (IGAN). METHODS: This is a case-control study
      with three groups: ADPKD (n = 54), IGAN (n = 58) and healthy controls (n = 86).
      The major plasma aminothiols with their redox species were examined: homocysteine
      (Hcy), cysteinglycine (CG), cysteine (Cys) and glutathione (GSH). The redox ratio
      was the ratio of reduced free and oxidized aminothiols in plasma. We investigated
      malonedialdehyde (MDA) and advanced oxidation protein products (AOPP), and ten
      single nucleotide polymorphisms of antioxidant enzymes. RESULTS: Patients had
      elevated oxidized free Hcy and Cys with associated low redox ratios - most
      pronounced in IGAN. Patients with IGAN had elevated AOPP and possibly MDA.
      Oxidized free Hcy and Cys with redox ratios were correlated to AOPP, MDA and
      proteinuria. Furthermore, there was an independent relationship to parathyroid
      hormone (PTH). IGAN had an elevated frequency of Val16Ala SNP rs4880, which
      influence the function of mitochondrial superoxide dismutase 2 (p = 0.03).
      CONCLUSIONS: Patients with ADPKD and IGAN have evidence of oxidative stress from
      stage 1 to 4 - most pronounced in IGAN. In patients, aminothiol redox biomarkers
      were correlated to AOPP, proteinuria and PTH, which are known prognostic markers
      in CKD. It may be possible that oxidative stress influences PTH dysregulation in
      CKD. The association between IGAN and the redox related variant allele rs4880(C)
      might indicate a new susceptibility locus for IGAN, but this needs verification.

PMID- 29655961
TI  - Chimeric antigen receptor T cell therapy for non-Hodgkin lymphoma.
AB  - Non-Hodgkin Lymphoma (NHL) is the most common hematologic malignancy. More than
      20,000 people in United States, more than 37,000 people in Europe and more than
      199,000 people worldwide die of NHL every year. Recent advances in
      immunotherapeutic approaches for cancer have resulted in development of new
      classes of very effective immunotherapeutic approaches including chimeric antigen
      receptor T (CAR-T) cell therapy that are designed to bypass cancer immune
      evasion. Here, we review recent advances in CAR-T cell therapy for NHL. US food
      and drug administration (FDA) recently approved axicabtagene ciloleucel
      (Yescarta) a CD19 CAR T cell therapy for treatment of relapsed refractory diffuse
      large B cell lymphoma (DLBCL), high grade lymphoma, and primary mediastinal B
      cell lymphoma (PMBCL). Approval of Yescarta and rapid development of other CAR T
      cell therapies at various stages of development are opening up the door for a new
      wave of CAR T cell therapies that will dramatically change the way we treat NHL
      and hopefully other malignancies in the near future.

PMID- 29655962
TI  - Novel targets and technologies for CAR-T cells in multiple myeloma and acute
      myeloid leukemia.

PMID- 29655963
TI  - Abortion training in US obstetrics and gynecology residency programs.
AB  - BACKGROUND: Nearly 15 years ago, 51% of US obstetrics and gynecology residency
      training program directors reported that abortion training was routine, 39%
      reported training was optional, and 10% did not have training. The status of
      abortion training now is unknown. OBJECTIVE: We sought to determine the current
      status of abortion training in obstetrics and gynecology residency programs.
      STUDY DESIGN: Through surveying program directors of US obstetrics and gynecology
      residency training programs, we conducted a cross-sectional study on the
      availability and characteristics of abortion training. Training was defined as
      routine if included in residents' schedules with individuals permitted to opt
      out, optional as not in the residents' schedules but available for individuals to
      arrange, and not available. Findings were compared between types of programs
      using bivariate analyses. RESULTS: In all, 190 residency program directors (79%)
      responded. A total of 64% reported routine training with dedicated time, 31%
      optional, and 5% not available. Routine, scheduled training was correlated with
      higher median numbers of uterine evacuation procedures. While the majority
      believed their graduates to be competent in first-trimester aspiration (71%),
      medication abortion (66%), and induction termination (67%), only 22% thought
      graduates were competent in dilation and evacuation. Abortion procedures varied
      by clinical indication, with some programs limiting cases to pregnancy
      complication, fetal anomaly, or demise. CONCLUSION: Abortion training in
      obstetrics and gynecology residency training programs has increased since 2004,
      yet many programs graduate residents without sufficient training to provide
      abortions for any indication, as well as dilation and evacuation. Professional
      training standards and support for family planning training have coincided with
      improved training, but there are still barriers to understand and overcome.

PMID- 29655964
TI  - Infant outcome after complete uterine rupture.
AB  - BACKGROUND: Complete uterine rupture is a rare peripartum complication often
      associated with a catastrophic outcome for both mother and child. However, little
      has been written based on large data sets about maternal and infant outcome after
      complete ruptures. This is partly due to the rarity of the event and the serious
      maternal and infant outcome; it is also partly due to the use of international
      diagnostic codes that do not differentiate between the less catastrophic partial
      rupture and more catastrophic complete uterine rupture. As uterine rupture is
      expected to increase due to increased cesarean delivery rates worldwide, it is
      important to know more completely about the outcome following complete uterine
      rupture. OBJECTIVE: We sought to explore risk factors associated with poor infant
      outcome in cases of complete uterine rupture. STUDY DESIGN: This population-based
      study used data from the Medical Birth Registry of Norway, the Patient
      Administration System, and medical records. We included births with complete
      uterine rupture after start of labor in all maternity units in Norway during the
      period 1967 through 2008 (n = 244 births), identified among 2,455,797 births.
      Uterine ruptures were identified and further studied through a review of medical
      records. We estimated the associations between infant outcomes and demographic
      and labor risk factors using logistic regression analyses. Odds ratios with 95%
      confidence intervals for each risk factor were determined after adjustment for
      demographic factors and period of birth. The main outcome measure was infant
      outcome: healthy infant, intrapartum/infant deaths, hypoxic ischemic
      encephalopathy, and admission to the neonatal intensive care unit. RESULTS: We
      identified 109 (44.7%) healthy infants, 56 (23.0%) infants needing neonatal
      intensive care unit admission, 64 (26.2%) intrapartum/infant deaths, and 15
      (6.1%) infants with hypoxic ischemic encephalopathy. The highest number of
      intrapartum/infant deaths occurred in 1967 through 1977 (51.6%) and the fewest in
      2000 through 2008 (15.0%). Unscarred uterine ruptures did not significantly
      increase intrapartum/infant deaths compared to scarred uterine ruptures.
      Placental separation and/or fetal extrusion had the highest odds ratio for
      intrapartum/infant deaths (odds ratio, 17.9; 95% confidence interval, 7.5-42.4).
      Time-to-delivery interval <20 minutes resulted in fewest intrapartum/infant
      deaths (9.9%), although there were 2 deaths at 10-minute interval. Time to
      delivery >30 minutes vs <20 minutes increased risk of death (odds ratio, 16.7;
      95% confidence interval, 6.4-43.5). CONCLUSION: Intrapartum/infant death after
      complete uterine rupture decreased significantly over the decades. Time to
      delivery >30 minutes and placental separation and/or fetal extrusion had the
      highest association with intrapartum/infant deaths after complete uterine
      rupture. Time to delivery <20 minutes limited the incidence of intrapartum/infant
      deaths.

PMID- 29655965
TI  - Cesarean delivery in the United States 2005 through 2014: a population-based
      analysis using the Robson 10-Group Classification System.
AB  - BACKGROUND: Cesarean delivery has increased steadily in the United States over
      recent decades with significant downstream health consequences. The World Health
      Organization has endorsed the Robson 10-Group Classification System as a global
      standard to facilitate analysis and comparison of cesarean delivery rates.
      OBJECTIVE: Our objective was to apply the Robson 10-Group Classification System
      to a nationwide cohort in the United States over a 10-year period. STUDY DESIGN:
      This population-based analysis applied the Robson 10-Group Classification System
      to all births in the United States from 2005 through 2014, recorded in the 2003
      revised birth certificate format. Over the study 10-year period, 27,044,217
      deliveries met inclusion criteria. Five parameters (parity including previous
      cesarean, gestational age, labor onset, fetal presentation, and plurality),
      identifiable on presentation for delivery, were used to classify all women
      included into 1 of 10 groups. RESULTS: The overall cesarean rate was 31.6%. Group
      3 births (singleton, term, cephalic multiparas in spontaneous labor) were most
      common, while group-5 births (those with a previous cesarean) accounted for the
      most cesarean deliveries increasing from 27% of all cesareans in 2005 through
      2006 to >34% in 2013 through 2014. Breech pregnancies (groups 6 and 7) had
      cesarean rates >90%. Primiparous and multiparous women who had a prelabor
      cesarean (groups 2b and 4b) accounted for over one quarter of all cesarean
      deliveries. CONCLUSION: Women with a previous cesarean delivery represent an
      increasing proportion of cesarean deliveries. Use of the Robson criteria allows
      standardized comparisons of data and identifies clinical scenarios driving
      changes in cesarean rates. Hospitals and health organizations can use the Robson
      10-Group Classification System to evaluate quality and processes associated with
      cesarean delivery.

PMID- 29655966
TI  - Secular trends in the epidemiology of Clostridium difficile infection (CDI) at a
      tertiary care hospital in Barcelona, 2006-2015: A prospective observational
      study.
AB  - OBJECTIVE: Describe secular trends in the epidemiology and outcome of Clostridium
      difficile infection (CDI) at a tertiary hospital. METHODS: All consecutive
      primary CDI episodes in adults (January 2006-December 2015) were included. CDI
      was diagnosed on the presence of diarrhoea and a positive stool test for C.
      difficile toxin A and/or B. To define trends, a time-series analysis was
      performed using yearly data on demographics, clinical characteristics,
      management, antimicrobial treatment, and outcome of CDI. Patients were followed
      up for three months after the diagnosis. RESULTS: There were 724 CDI episodes.
      Over the period from 2006 to 2015, the incidence rose from 0.18 episodes/1000
      admissions to 0.26 episodes (relative rate [RR] 1.43; 95%CI, 1.02-2.00; P =
      0.035). Median Charlson comorbidity index increased from 2 (IQR 1-3) to 4 (IQR 2
      4) (RR 1.65; 95%CI, 1.12-2.41; P = 0.005). Overall, 80.4% of patients received
      proton pump inhibitors (PPIs) prior to CDI, and the percentage of PPI
      discontinuations rose from 2.3% to 20.4% (RR 8.80; 95%CI 1.20-64.36; P = 0.006).
      Management of non-Clostridium antibiotics also changed: antibiotic withdrawals or
      switches increased from 4.2% to 29.2% (RR 7.00; 95%CI 1.68-29.15, P = 0.001).
      Regarding CDI treatment, the percentage of patients treated with metronidazole
      decreased (88.9% vs 52.6%) (RR 0.59 (0.48-0.73), P < 0.001), whereas the
      percentage receiving vancomycin increased (1.9% vs 32.6%) (RR 17.62 (2.47
      125.49), P < 0.001). The percentages of cures, deaths, and first recurrences did
      not significantly change over the 10-year period. CONCLUSIONS: Changes in CDI
      management were associated with a stable prognosis (percentage of cures and first
      recurrences), even though affected patients had a greater number of comorbidities
      over time.

PMID- 29655967
TI  - Visual search for verbal material in patients with obsessive-compulsive disorder.
AB  - This study aimed at investigating attentional mechanisms in obsessive-compulsive
      disorder (OCD) by analysing how visual search processes are modulated by normal
      and obsession-related distracting information in OCD patients and whether these
      modulations differ from those observed in healthy people. OCD patients were asked
      to search for a target word within distractor words that could be
      orthographically similar to the target, semantically related to the target,
      semantically related to the most typical obsessions/compulsions observed in OCD
      patients, or unrelated to the target. Patients' performance and eye movements
      were compared with those of individually matched healthy controls. In controls,
      the distractors that were visually similar to the target mostly captured
      attention. Conversely, patients' attention was captured equally by all kinds of
      distractor words, whatever their similarity with the target, except obsession
      related distractors that attracted patients' attention less than the other
      distractors. OCD had a major impact on the mostly subliminal mechanisms that
      guide attention within the search display, but had much less impact on the
      distractor rejection processes that take place when a distractor is fixated.
      Hence, visual search in OCD is characterized by abnormal subliminal, but not
      supraliminal, processing of obsession-related information and by an impaired
      ability to inhibit task-irrelevant inputs.

PMID- 29655968
TI  - Mediation of the bidirectional relations between obesity and depression among
      women.
AB  - Past research established that obesity increases risk for development of
      depression, and depression increases risk for development of obesity. The current
      study tested physical impairment (difficulty with instrumental activities of
      daily living), social dysfunction (low social support and high social strain),
      and emotional eating (using food to cope with stress) as mediators of the
      bidirectional, longitudinal relations between depression and obesity. A national
      sample of mid-life adults in the United States (N = 7108) was assessed at three
      time points over 18 years. Depression predicted increases in obesity, and obesity
      predicted increases in depression, for women but not for men. Among women, path
      analyses revealed that physical impairment, social dysfunction, and emotional
      eating mediated development of obesity from depression, and that physical
      impairment and emotional eating mediated development of depression from obesity.
      These results suggest that prevention or treatment of obesity-linked depression
      and depression-linked obesity in women may need to address multiple connections
      between these disorders.

PMID- 29655969
TI  - Affiliate stigma and depression in caregivers of children with Autism Spectrum
      Disorders in China: Effects of self-esteem, shame and family functioning.
AB  - The present study aimed to investigate affiliate stigma and depression in
      caregivers of children with Autism Spectrum Disorders (ASD) in China and to
      examine the predictive effects of self-esteem, shame proneness and family
      functioning. Two hundred and sixty-three primary caregivers of children with
      autism in Mainland China participated in the survey. The results suggested that
      affiliate stigma in caregivers of children with autism was prevalent and severe;
      their depressive symptoms were significantly more severe than the national norm
      of the similar age group. Low self-esteem, high shame proneness and poor family
      adaptability were associated with experience of affiliate stigma and heightened
      depressive symptoms. Affiliate stigma partially mediated the links between self
      esteem/ shame proneness/family adaptability and depression levels. This study was
      the first one to measure affiliate stigma on caregivers of children with ASD in
      mainland China using a quantitative method. The results highlight the necessity
      and importance of de-stigmatization for the caregivers of children with autism
      and suggest that interventions to improve self-esteem, reduce experience of shame
      and to enhance family functioning might be effective.

PMID- 29655970
TI  - Suicide after hospital contact for psychiatric assessment in Hong Kong: A long
      term cohort study.
AB  - There are few long-term studies on suicide in psychiatric settings in China. The
      objective of this study was to evaluate the long term suicide risk and its
      associated factors after the initial psychiatric assessment. Demographic and
      clinical data of adult subjects receiving psychiatric assessment between 1996 and
      2000 in a district hospital in Hong Kong were retrieved from the hospital
      computer system. Data were matched with completed suicides before June 30 2015 as
      recorded by the Coroner's Office. From a total of 4078 subjects identified, there
      were 152 (3.7%) recorded suicides; one-fifth of suicides occurred within one
      year, and half within 5 years. Cox regression analysis revealed that the risk of
      suicide after the initial psychiatric assessment was positively associated with
      deliberate self-harm (Hazard ratio = 2.1; 95%CI = 1.5-3.0; p < 0.001), and
      negatively associated with 'no psychiatric disorder' (Hazard ratio = 0.4; 95%CI =
      0.2-0.6; p = 0.001). The overall suicide risk for those diagnosed to have a
      psychiatric disorder was 4.4%; 4.5% for men and 4.3% for women. Deliberate self
      harm and having a psychiatric disorder at the time of assessment are significant
      risk factors of suicide. Appropriate treatment of psychiatric disorders and
      comprehensive management of deliberate self-harm are important for suicide
      prevention.

PMID- 29655971
TI  - Predictive validity and gender differences in a biopsychosocial model of violence
      risk assessment in acute psychiatry.
AB  - Current violence risk assessment methods seem to have reached an upper limit of
      accuracy. More comprehensive biopsychosocial models may improve on existing
      methods. Research on gender differences concerning risk factors of violence is
      scarce and inconclusive. In this prospective study from an acute psychiatric
      ward, all patients admitted from March 2012 to March 2013 were included.
      Predictive validity and potential gender differences in a biopsychosocial model
      of violence risk assessment consisting of a psychosocial checklist (Violence risk
      screening-10, V-RISK-10), a patient's self-report risk scale (SRS), total
      cholesterol (TC) and high-density lipoprotein cholesterol (HDL) were examined in
      an inpatient (N = 348) and a 3-months follow-up (N = 101) sample. Overall
      increases in explained variances and predictive values were small and non
      significant compared to V-RISK-10 alone. In the inpatient sample, HDL contributed
      significantly to the model for men but not for women. In the follow-up sample,
      SRS contributed significantly for the whole sample. Results indicated that the
      biopsychosocial model we tested partially improved accuracy of violence risk
      assessments in acute psychiatry and that gender differences may exist.

PMID- 29655972
TI  - Effectiveness and safety of anti-TNF therapy for inflammatory bowel disease in
      liver transplant recipients for primary sclerosing cholangitis: A nationwide case
      series.
AB  - BACKGROUND: There is a lack of consensus regarding the treatment of inflammatory
      bowel disease (IBD) after liver transplantation (LT) forprimary sclerosing
      cholangitis (PSC). AIM: To investigate the safety and effectiveness of anti-TNF
      therapy in patients with IBD after a LT for PSC. METHODS: We reviewed the medical
      files of all of the IBD patients who underwent a LT for PSC and who were treated
      with anti-TNF therapy at 23 French liver transplantation centers between 1989 and
      2012. RESULTS: Eighteen patients (12 with ulcerative colitis and 6 who had
      Crohn's disease) were recruited at 9 LT centers. All of these patients received
      infliximab or adalimumab following their LT, and the median duration of their
      anti-TNF treatment was 10.4 months. The most frequent concomitant
      immunosuppressive treatment comprised a combination of tacrolimus and
      corticosteroids. Following anti-TNF therapy induction, a clinical response was
      seen in 16/18 patients (89%) and clinical remission in 10 (56%). At the end of
      the anti-TNF treatment or at the last follow-up examination (the median follow-up
      was 20.9 months), a clinical response was achieved in 12 patients (67%) and
      clinical remission in 7 (39%). A significant endoscopic improvement was observed
      in 9 out of 14 patients and a complete mucosal healing in 3 out of 14 patients
      (21%). Six patients experienced a severe infection. These were due to
      cholangitis, cytomegalovirus (CMV) infection, Clostridium difficile,
      cryptosporidiosis, or Enterococcus faecalis. Three patients developed colorectal
      cancer after LT, and two patients died during the follow-up period. CONCLUSIONS:
      Anti-TNF therapy proved to be effective for treating IBD after LT for PSC.
      However, as 17% of the patients developed colorectal cancer during the follow-up,
      colonoscopic annual surveillance is recommended after LT, as specified in the
      current guidelines.

PMID- 29655973
TI  - Robust workflow and instrumentation for cryo-focused ion beam milling of samples
      for electron cryotomography.
AB  - Electron cryotomography is able to visualize macromolecular complexes in their
      cellular context, in a frozen-hydrated state, and in three dimensions. The
      method, however, is limited to relatively thin samples. Cryo-focused ion beam
      (FIB) milling is emerging as a powerful technique for sample thinning prior to
      cryotomography imaging. Previous cryo-FIB milling reports utilized custom-built
      non-standard equipment. Here we present a workflow and the required commercially
      available instrumentation to either implement the method de novo, or as an
      upgrade of pre-existing dual beam milling instruments. We introduce two
      alternative protocols and the respective sample holders for milling. The "bare
      grid holder" allows for milling on plain grids, having the advantage of enabling
      relatively shallow milling angles for wedge geometries. The "Autogrid holder" is
      designed for milling grids clamped into a mechanical support ring (Autogrid),
      resulting in increased stability for lamella geometries. We applied the workflow
      to prepare samples and record high-quality tomograms of diverse model organisms,
      including infected and uninfected HeLa cells, amoebae, yeast, multicellular
      cyanobacteria, Pseudomonas aeruginosa and Escherichia coli cells. The workflow
      will contribute to the dissemination of electron cryotomography of cryo-FIB
      milled samples in the biological sciences.

PMID- 29655974
TI  - tACS-mediated modulation of the auditory steady-state response as seen with MEG.
AB  - BACKGROUND: Previous studies have shown that transcranial electrical stimulation
      can be successfully applied during simultaneous MEG measurements. In particular,
      using beamforming they have established that changes of stimulus induced as well
      as evoked activity can be inspected during transcranial alternating current
      stimulation (tACS). OBJECTIVE/HYPOTHESIS: We studied tACS-mediated changes of the
      auditory steady-state response (ASSR), hypothesizing that-due to the putatively
      inhibitory role of alpha oscillations-these evoked responses would be diminished.
      METHODS: We compared ASSRs in conditions with and without 12-Hz and 6.5-Hz
      sinusoidal 1.5 mA tACS, applied bilaterally over temporal areas. Source-level
      activity was estimated using a linearly constrained minimum variance beamformer
      and compared across tACS conditions using paired t-tests following a condition
      internal normalization procedure. CONCLUSIONS: By separating the electrical and
      auditory stimulation to non-overlapping parts of the frequency spectrum, we were
      able to compare auditory-evoked steady-state activity across tACS conditions. We
      observed a significant decrease in normalized ASSR power in the 12-Hz tACS
      condition, illustrating that tACS could induce immediate changes in auditory
      evoked activity. This study sets a methodology to further interrogate the causal
      roles of oscillatory dynamics in auditory cortices, as well as suggests
      perspectives for employing tACS in clinical contexts.

PMID- 29655975
TI  - Vestibular and balance function is often impaired in children with profound
      unilateral sensorineural hearing loss.
AB  - RATIONALE: Children with unilateral deafness could have concurrent vestibular
      dysfunction which would be associated with balance deficits and potentially
      impair overall development. The prevalence of vestibular and balance deficits
      remains to be defined in these children. METHODS: Twenty children with unilateral
      deafness underwent comprehensive vestibular and balance evaluation. RESULTS:
      Retrospective review revealed that more than half of the cohort demonstrated some
      abnormality of the vestibular end organs (otoliths and horizontal canal), with
      the prevalence of end organ specific dysfunction ranging from 17 to 48% depending
      on organ tested and method used. In most children, impairment occurred only on
      the deaf side. Children with unilateral deafness also displayed significantly
      poorer balance function than their normal hearing peers. CONCLUSIONS: The
      prevalence of vestibular dysfunction in children with unilateral deafness is high
      and similar to that of children with bilateral deafness. Vestibular and balance
      evaluation should be routine and the functional impact of combined vestibulo
      cochlear sensory deficits considered.

PMID- 29655976
TI  - DCD consensus and futility in liver transplantation.

PMID- 29655977
TI  - Dexmedetomidine or fentanyl? Cardiovascular stability and analgesia during
      propofol-ketamine total intravenous anaesthesia in experimental pigs.
AB  - OBJECTIVE: To compare cardiovascular function and response to nociception during
      total intravenous anaesthesia in pigs with propofol, ketamine and either
      dexmedetomidine or fentanyl administered as a continuous infusion. STUDY DESIGN:
      Blinded, randomized, balanced, crossover study ANIMALS: Eight immunocastrated
      male, mixed breed pigs with a mean +/- standard deviation body weight of 26.4 +/-
      1.9 kg for dexmedetomidine and 27.5 +/- 3.8 kg for fentanyl treatment. METHODS:
      The animals were anaesthetized twice with either propofol-ketamine
      dexmedetomidine (DEX) or fentanyl (FENT). DEX was infused at 2, 4 and 8 MUg kg-1
      hour-1 and FENT at 25, 50 and 100 MUg kg-1 hour-1. Each infusion rate was
      administered for 80 minutes prior to commencing the next. Heart rate (HR), 3-lead
      electrocardiogram, systolic, mean and diastolic arterial blood pressure (SAP,
      MAP, DAP) in addition to cardiac output measured by transpulmonary thermodilution
      was used to monitor cardiovascular function. Mechanical and electrical
      stimulation (nociceptive withdrawal reflex, NWR) was used to elicit nociceptive
      responses. Similar anaesthetic depth was determined based on the NWR response.
      Cardiovascular parameters were compared statistically at this time. Additionally,
      response to nociceptive stimulation and cardiovascular response over time were
      compared. RESULTS: DEX-treated pigs had significantly higher HR, SAP, DAP, MAP,
      systemic vascular resistance, haemoglobin concentration, content of oxygen in
      arterial and venous blood and oxygen delivery index than FENT-treated pigs at
      similar anaesthetic depth, whereas stroke volume index was significantly higher
      in FENT. Motoric response to mechanical nociceptive stimulation was abolished
      prior to any decrease in NWR response in FENT, whereas the two responses
      decreased more in unison in DEX. The cardiovascular response to nociception was
      less pronounced in DEX than in FENT. CONCLUSIONS AND CLINICAL RELEVANCE: Propofol
      combined with ketamine and either fentanyl or dexmedetomidine provides stable
      cardiovascular conditions in normovolaemic, healthy pigs. Based on cardiovascular
      response and depression of NWR, dexmedetomidine apparently provides superior
      analgesia to fentanyl.

PMID- 29655978
TI  - Sitagliptin prevents isoproterenol-induced myocardial infarction in rats by
      modulating nitric oxide synthase enzymes.
AB  - Ischemic heart disease is a common cause of mortality worldwide. Sitagliptin is a
      new anti-diabetic drug acting as dipeptidyl peptidase-4 (DPP-4) inhibitor. The
      study investigated the ability of sitagliptin to prevent pathological changes of
      isoproterenol- (ISO-) induced myocardial injury in rats. The role of nitric oxide
      (NO) was also reported. Rats were assorted into six groups (n = 7) and treated
      for 12 days. Group 1: normal control, received normal saline. Group 2,
      sitagliptin control, received sitagliptin (10 mg/kg, orally). Group 3, ISO group,
      received isoproterenol (ISO) (100 mg/kg, i.p.). Group 4, sitagliptin + ISO, co
      treated with sitagliptin plus ISO. Group 5, L-NNA + ISO, co-treated with L-NG
      nitro arginine (L-NNA) (25 mg/kg, orally) plus ISO. Group 6, sitagliptin + L-NNA
      + ISO, co-treated with sitagliptin plus ISO plus L-NNA. Blood glucose, serum
      creatine kinase-MB (CK-MB, and cardiac tissue parameters of oxidative stress
      parameters and NO, along with histopathological examination, and
      immunohistochemical study of inducible NO synthase (iNOS) expression were done.
      The results showed that sitagliptin caused a significant reduction in CK-MB, and
      attenuated histopathological damage-induced by ISO. Its effect was associated
      with a significant decrease in oxidative stress parameters, NO contents as well
      as by a significant decrease in the expression of iNOS in cardiac tissue. The
      protective effect of sitagliptin was abrogated by coadministartion of L-NNA, a
      selective inhibitor of both endothelial NOS (eNOS) and neuronal NOS (nNOS). In
      conclusion, sitagliptin ameliorates ISO-induced myocardial injury via antioxidant
      effects and modulation of NOS enzymes.

PMID- 29655979
TI  - Discovery of chiral dihydropyridopyrimidinones as potent, selective and orally
      bioavailable inhibitors of AKT.
AB  - During the course of our research efforts to develop potent and selective AKT
      inhibitors, we discovered enatiomerically pure substituted
      dihydropyridopyrimidinones (DHP) as potent inhibitors of protein kinase B/AKT
      with excellent selectivity against ROCK2. A key challenge in this program was the
      poor physicochemical properties of the initial lead compound 5. Integration of
      structure-based drug design and physical properties-based design resulted in
      replacement of a highly hydrophobic poly fluorinated aryl ring by a simple
      trifluoromethyl that led to identification of compound 6 with much improved
      physicochemical properties. Subsequent SAR studies led to the synthesis of new
      pyran analog 7 with improved cell potency. Further optimization of
      pharmacokintetics properties by increasing permeability with appropriate
      fluorinated alkyl led to compound 8 as a potent, selective AKT inhibitors that
      blocks the phosphorylation of GSK3beta in vivo and had robust, dose and
      concentration dependent efficacy in the U87MG tumor xenograft model.

PMID- 29655981
TI  - Modular synthesis of new C-aryl-nucleosides and their anti-CML activity.
AB  - The C-aryl-ribosyles are of utmost interest for the development of antiviral and
      anticancer agents. Even if several synthetic pathways have been disclosed for the
      preparation of these nucleosides, a direct, few steps and modular approaches are
      still lacking. In line with our previous efforts, we report herein a one step -
      eco-friendly beta-ribosylation of aryles and heteroaryles through a direct
      Friedel-Craft ribosylation mediated by bismuth triflate, Bi(OTf)3. The resulting
      carbohydrates have been functionalized by cross-coupling reactions, leading to a
      series of new C-aryl-nucleosides (32 compounds). Among them, we observed that 5d
      exerts promising anti-proliferative effects against two human Chronic Myeloid
      Leukemia (CML) cell lines, both sensitive (K562-S) or resistant (K562-R) to
      imatinib, the "gold standard of care" used in this pathology. Moreover, we
      demonstrated that 5d kills CML cells by a non-conventional mechanism of cell
      death.

PMID- 29655980
TI  - Evaluation of novel TGR5 agonist in combination with Sitagliptin for possible
      treatment of type 2 diabetes.
AB  - TGR5 is a member of G protein-coupled receptor (GPCR) superfamily, a promising
      molecular target for metabolic diseases. Activation of TGR5 promotes secretion of
      glucagon-like peptide-1 (GLP-1), which activates insulin secretion. A series of 2
      thio-imidazole derivatives have been identified as novel, potent and orally
      efficacious TGR5 agonists. Compound 4d, a novel TGR5 agonist, in combination with
      Sitagliptin, a DPP-4 inhibitor, has demonstrated an adequate GLP-1 secretion and
      glucose lowering effect in animal models, suggesting a potential clinical option
      in treatment of type-2 diabetes.

PMID- 29655982
TI  - Polyprenylated polycyclic acylphloroglucinol: Angiogenesis inhibitor from
      Garcinia multiflora.
AB  - A new polyprenylated polycyclic acylphloroglucinol, garcimultiflorone K (1), has
      been isolated from the stems of Garcinia multiflora, together with two known
      compounds, garcimultiflorone A (2) and garcimultiflorone B (3). The structure of
      new compound 1 was determined through spectroscopic methods including 1D and 2D
      NMR and MS analyses. The anti-angiogenic and anti-cancer effects of compounds 1-3
      were evaluated in human endothelial progenitor cells (EPCs) and cancer cells. Of
      these, garcimultiflorone K (1) displayed the most potent anti-angiogenic property
      by suppressing cell growth and tube formation of EPCs. Compound 1 also exhibited
      growth-inhibitory activities against human hepatocellular carcinoma cell line SK
      Hep-1 and hormone refractory prostate cancer cell line PC-3 with GI50 values of
      4.3 +/- 1.6 and 6.6 +/- 0.4 MUM, respectively.

PMID- 29655983
TI  - Catalytic asymmetric synthesis of alpha-methyl-p-boronophenylalanine.
AB  - p-Boronophenylalanine (l-BPA) is applied in clinical settings as a boron carrier
      for boron neutron capture therapy (BNCT) to cure malignant melanomas. Structural
      modification or derivatization of l-BPA, however, to improve its uptake
      efficiency into tumor cells has scarcely been investigated. We successfully
      synthesized (S)-2-amino-3-(4-boronophenyl)-2-methylpropanoic acid in
      enantioenriched form as a novel candidate molecule for BNCT. Key steps to enhance
      the efficiency of this synthesis were enantioselective alkylation of N-protected
      alanine tert-butyl ester with a Maruoka catalyst and Miyaura borylation reaction
      to install the boron functionality.

PMID- 29655984
TI  - Motor affordance at home for infants living in poverty: A feasibility study.
AB  - PURPOSE: To determine the feasibility of completing a randomized clinical trial
      of motor affordance program at home for infants living in poverty. METHODS:
      Fourteen infants living in poverty were randomized assigned to groups:
      intervention at 1st month (G-1), and at 2nd month (G-2). They were assessed into
      3 visits: Visit 1 (baseline), Visit 2 (after 4 weeks), and Visit 3 (after 8
      weeks). The motor affordance program was provided at home by parents/caregivers.
      To determine feasibility of the program, descriptive data was used. Effect sizes
      and non-parametric analysis were performed for motor and affordances at home.
      RESULTS: The motor affordance program was considered feasible and showed
      improvement on affordances at home and motor performance only for G-2.
      CONCLUSION: Amplifying motor affordance at home may be considered appropriate for
      future clinical trials. It may be an efficient/low-cost early intervention
      strategy for infants at environmental risk.

PMID- 29655985
TI  - PEX13 Enters the RING, Lives Fast, Dies Young.

PMID- 29655986
TI  - Targeting Intrinsically Disordered Transcription Factors: Changing the Paradigm.
AB  - Increased understanding of intrinsically disordered proteins (IDPs) and protein
      regions has revolutionized our view of the relationship between protein structure
      and function. Data now support that IDPs can be functional in the absence of a
      single, fixed, three-dimensional structure. Due to their dynamic morphology, IDPs
      have the ability to display a range of kinetics and affinity depending on what
      the system requires, as well as the potential for large-scale association.
      Although several studies have shed light on the functional properties of IDPs,
      the class of intrinsically disordered transcription factors (TFs) is still poorly
      characterized biophysically due to their combination of ordered and disordered
      sequences. In addition, TF modulation by small molecules has long been considered
      a difficult or even impossible task, limiting functional probe development.
      However, with evolving technology, it is becoming possible to characterize TF
      structure-function relationships in unprecedented detail and explore avenues not
      available or not considered in the past. Here we provide an introduction to the
      biophysical properties of intrinsically disordered TFs and we discuss recent
      computational and experimental efforts toward understanding the role of
      intrinsically disordered TFs in biology and disease. We describe a series of
      successful TF targeting strategies that have overcome the perception of the
      "undruggability" of TFs, providing new leads on drug development methodologies.
      Lastly, we discuss future challenges and opportunities to enhance our
      understanding of the structure-function relationship of intrinsically disordered
      TFs.

PMID- 29655987
TI  - Overcoming safety challenges in CO therapy - Extracorporeal CO delivery under
      precise feedback control of systemic carboxyhemoglobin levels.
AB  - Carbon monoxide (CO) has demonstrated therapeutic potential in multiple
      inflammatory conditions including intensive care applications such as organ
      transplantation or sepsis. Approaches to translate these findings into future
      therapies, however, have been challenged by multiple hurdles including handling
      and toxicity issues associated with systemic CO delivery. Here, we describe a
      membrane-controlled Extracorporeal Carbon Monoxide Release System (ECCORS) for
      easy implementation into Extracorporeal Membrane Oxygenation (ECMO) setups, which
      are being used to treat cardiac and respiratory diseases in various intensive
      care applications. Functionalities of the ECCORS were investigated in a pig model
      of veno-arterial ECMO. By precisely controlling CO generation and delivery as a
      function of systemic carboxyhemoglobin levels, the system allows for an immediate
      onset of therapeutic CO-levels while preventing CO-toxicity. Systemic
      carboxyhemoglobin levels were profiled in real-time by monitoring exhaled CO
      levels as well as by pulse oximetry, enabling self-contained and automatic
      feedback control of CO generation within ECCORS. Machine learning based
      mathematical modeling was performed to increase the predictive power of this
      approach, laying foundation for high precision systemic CO delivery concepts of
      tomorrow.

PMID- 29655988
TI  - Tissue engineering: Still facing a long way ahead.
AB  - Tissue engineering (TE) has provided promising perspectives to overcome the
      limited efficiency of the conventional treatment options or organ
      transplantation. Considerable advances in stem cell therapies and biomaterials
      science and development of delivery systems capable to mimic the production of
      growth factors may offer treatment breakthroughs in a variety of diseases.
      Meanwhile, proper vascularization, creation of the complex tissues, tissue
      quality, functional integration between the graft and host tissues, and the
      potential risks of chromosomal instability, mutations, tumorigenesis, or
      unexpected events have remained challenging. Furthermore, the promising results
      of the in vitro or in vivo studies may not be applicable to the clinical
      settings. These issues remind us to avoid the simplistic views or exaggerated
      optimism regarding the novel technologies including TE. This review highlights
      the advances in TE including its promising potential for clinical applications
      and the potential solutions for common pitfalls with a special look at the role
      of the computational modeling that may facilitate translation of the basic
      research findings into the clinical applications.

PMID- 29655989
TI  - In vivo migration of mesenchymal stem cells to burn injury sites and their
      therapeutic effects in a living mouse model.
AB  - Mesenchymal stem cell (MSC)-based therapy has emerged as a promising therapeutic
      strategy for tissue regeneration and repair. In this study, we non-invasively
      monitored the tracking of MSCs toward burn injury sites using MSCs expressing
      firefly luciferase (Fluc) gene in living mice, and evaluated the effects of the
      MSCs at the injury site. Murine MSCs co-expressing Fluc and green fluorescent
      protein (GFP) were established using a retroviral system (referred to as
      MSC/Fluc). To evaluate the ability of MSC migration toward burn injury sites,
      cutaneous burn injury was induced in the dorsal skin of mice. MSC/Fluc was
      intravenously administrated into the mice model and bioluminescence imaging (BLI)
      was performed to monitor MSC tracking at designated time points. BLI signals of
      MSC/Fluc appeared in burn injury lesions at 4 days after the cell injection and
      then gradually decreased. Immunoblotting analysis was conducted to determine the
      expression of neovascularization-related genes such as TGF-beta1 and VEGF in
      burnt skin. The levels of TGF-beta1 and VEGF were higher in the MSC/Fluc-treated
      group than in the burn injury group. Our observations suggested that MSCs might
      assist burn wound healing and that MSCs expressing Fluc could be a useful tool
      for optimizing MSC-based therapeutic strategies for burn wound healing.

PMID- 29655991
TI  - The effect of linkers on the self-assembling and anti-tumor efficacy of disulfide
      linked doxorubicin drug-drug conjugate nanoparticles.
AB  - Drug-drug conjugate nanoparticles (DDC NPs) is a potential method for overcoming
      poor solubility and nonspecific action in cancer therapy, which is based on its
      high drug loading efficiency and passive tumor-target properties. Our laboratory
      has prepared DOX-SS-DOX NPs based on disulfide-linked doxorubicin (DOX) drug-drug
      conjugate, which showed well physical stability and similar anti-tumor efficacy
      as liposomes. However, how structures of DDCs influence the self-assembling and
      anti-tumor efficacy is still seldom clarified and needs further investigation.
      Here, we discussed the role of linker types, length and linkage site in the NPs
      self-assembling and anti-tumor efficacy. A series of DOX prodrugs were prepared
      and all the prodrugs could self-assemble into NPs except DOX-SS-DOX (2),
      indicating the linker length played an important role during self-assembling
      process. The linkage sites and types of linker exhibited great influence on in
      vitro cytotoxicity and in vivo anti-tumor efficacy, particularly, modification on
      C-14 hydroxyl was more efficient for DOX release than on amino group. Besides,
      disulfide-bond was not cleaved and DOX-SH release did not occur in the metabolism
      process. The function of disulfide-bond was to enhance the release of DOX in the
      hydrolysis process. These findings is meaningful for effective prodrug NPs design
      for therapeutics.

PMID- 29655990
TI  - Inorganic kernel - Supported asymmetric hybrid vesicles for targeting delivery of
      STAT3-decoy oligonucleotides to overcome anti-HER2 therapeutic resistance of
      BT474R.
AB  - As a recombinant humanized monoclonal antibody that targets the extracellular
      region of HER2 tyrosine kinase receptor, trastuzumab (TRAZ) has demonstrated
      comparable clinical efficacy and improved survival in patients with HER2-positive
      breast cancer. Nevertheless, the therapeutic potential of TRAZ is often limited
      due to its frequent resistance to anti-HER2 therapy. Therefore, we investigate
      the reversal effect of STAT3-specific decoy oligonucleotides (STAT3-decoy ODNs)
      on TRAZ resistance, which contain the consensus sequence within the targeted gene
      promoter of STAT3. Considering the shortcomings of poor cellular permeability and
      rapid degradation in vivo limit the further clinical applications of ODNs, we
      report here an asymmetric hybrid lipid/polymer vesicles with calcium phosphate as
      the solid kernel (CaP@HA). Through hyaluronan-mediated CD44 targeting, the
      constructed vesicles can specifically carry STAT3-decoy ODNs into TRAZ-resistant
      breast cancer cells and then regulate TRAZ-induced apoptosis. In comparison with
      the native ones, ODNs packaged with CaP@HA showed significantly increased serum
      stability, cellular transfection, synergistic cytotoxicity and apoptosis in
      vitro. The improved TRAZ sensitization is attributed to the blockade of STAT3
      signaling as well as the expression of downstream target genes associated with
      TRAZ resistance. With the synergistic action of STAT3-decoy ODNs loaded CaP@HA,
      TRAZ inhibited the growth of its resistant breast cancer xenograft dramatically
      and induced significant tumor cell apoptosis in vivo. These results suggested
      that CaP@HA mediated targeted delivery of STAT3-decoy ODNs might be a promising
      new strategy to overcome anti-HER2 resistance in breast cancer therapy.

PMID- 29655992
TI  - Recurrent spontaneous cervical epidural hematoma in a parturient 11 hours after
      vaginal delivery without labor epidural analgesia.

PMID- 29655993
TI  - Ultrasound assessment of gastric contents at the end of pregnancy.

PMID- 29655994
TI  - Peripartum anaesthetic management of a patient with Brugada syndrome and
      myoadenylate deaminase deficiency.
AB  - Brugada syndrome is a rare electrophysiological cardiac disease which can result
      in serious arrhythmias and sudden cardiac death. Peripartum management is centred
      around avoiding arrhythmogenic drugs, including high doses of sodium channel
      blocking drugs such as bupivacaine. Myoadenylate deaminase deficiency, also known
      as adenosine monophosphate deaminase deficiency, is the commonest cause of
      myopathy in Caucasians. There is evidence that myoadenylate deaminase deficiency
      can predispose patients to developing malignant hyperthermia when exposed to
      specific anaesthetic agents. We present a case of a pregnant patient with both
      Brugada syndrome and myoadenylate deaminase deficiency, in which analgesic and
      general anaesthetic options for each condition presented potentially conflicting
      dilemmas for the delivery of intrapartum care.

PMID- 29655995
TI  - Microbial Effects on Immunity in HIV: Virus, Gender or Sexual Preference Induced?

PMID- 29655997
TI  - Retraction notice.

PMID- 29655996
TI  - A Genomic-clinicopathologic Nomogram for the Preoperative Prediction of Lymph
      Node Metastasis in Bladder Cancer.
AB  - Preoperative lymph node (LN) status is important for the treatment of bladder
      cancer (BCa). Here, we report a genomic-clinicopathologic nomogram for
      preoperatively predicting LN metastasis in BCa. In the discovery stage, 325 BCa
      patients from TCGA were involved and LN-status-related mRNAs were selected. In
      the training stage, multivariate logistic regression analysis was used to
      developed a genomic-clinicopathologic nomogram for preoperative LN metastasis
      prediction in the training set (SYSMH set, n=178). In the validation stage, we
      validated the nomogram using two independent sample sets (SYSUCC set, n=142; RJH
      set, n=104) with respect to its discrimination, calibration and clinical
      usefulness. As results, we identified five LN-status-related mRNAs, including
      ADRA1D, COL10A1, DKK2, HIST2H3D and MMP11. Then, a genomic classifier was
      developed to classify patients into high- and low-risk groups in the training
      set. Furthermore, a nomogram incorporating the five-mRNA-based classifier, image
      based LN status, transurethral resection (TUR) T stage, and TUR lymphovascular
      invasion (LVI) was constructed in the training set, which performed well in the
      training and validation sets. Decision curve analysis demonstrated the clinical
      value of our nomogram. Thus, our genomic-clinicopathologic nomogram shows
      favorable discriminatory ability and may aid in clinical decision-making,
      especially for cN-patients.

PMID- 29655998
TI  - Four possible cases of osteomalacia: The value of a multidisciplinary diagnostic
      approach.
AB  - Rickets and residual rickets are often encountered in Dutch archeological
      skeletal samples. However, no archeological Dutch paleopathological case of adult
      osteomalacia has been described in literature to date. This paper describes the
      first four archeological Dutch paleopathological cases of osteomalacia and
      assesses the value of the various modalities (macroscopic assessment, radiology
      and histology) that may be used for diagnosis. The skeletal remains investigated
      originate from the Meerenberg psychiatric hospital cemetery in Bloemendaal, the
      Netherlands, and date from 1891 - 1936. The remains of 69 adult individuals were
      inspected for macroscopic lesions which may be associated with osteomalacia. In
      cases suspect for osteomalacia, complimentary radiological and histological
      investigations (BSE-SEM and light microscopy) were performed. Macroscopically,
      four individuals presented with lesions (highly) suggestive of osteomalacia.
      Histological examination (both BSE-SEM and light microscopy) provided valuable
      information to come to an eventual diagnosis of osteomalacia in all four cases.
      Light microscopy proved to be an feasible alternative for BSE-SEM. The added
      value of radiological analyses was limited. The individuals identified were most
      likely patients in the psychiatric hospital, and the reason for their
      institutionalization and/or the regime in the institution may have played a role
      in the development of the osteomalacia observed.

PMID- 29655999
TI  - Ovarian hyperstimulation syndrome leading to ventriculoperitoneal shunt
      malfunction: Case report.
AB  - Ventriculoperitoneal shunt (VPS) insertion is a common neurosurgical procedure
      for hydrocephalus. Unfortunately, VPS malfunction is not uncommon, with an
      estimated cumulative rate of 32% at 5 years. As flow through the shunt is
      influenced by the pressure gradient between the ventricles and the peritoneal
      cavity, malfunction may be caused by elevated intra-abdominal pressure. We
      present a rare patient with ascites following ovarian hyperstimulation syndrome
      (OHSS) leading to shunt malfunction. OHSS is a potentially life-threatening
      complication of controlled ovarian stimulation caused by the administration of
      exogenous gonadotropins. In this patient clinical and radiological resolution of
      shunt dysfunction were achieved following peritoneocentesis. To our knowledge
      this is the first described case of OHSS leading to shunt malfunction,
      emphasizing the importance of awareness, early recognition and proper management
      of abdominal etiologies of VPS malfunction.

PMID- 29656000
TI  - Primary central nervous system lymphoma at the cerebellopontine angle mimicking a
      trigeminal schwannoma: A unique case report and literature review.
AB  - Primary central nervous system lymphoma (PCNSL) is an uncommon extranodal
      manifestation of non-Hodgkin's lymphoma with those presenting at the
      cerebellopontine angle (CPA) being rare presentations with limited reported cases
      in the literature. We report a 60-year old female presenting with PCNSL of the
      left CPA radiologically mimicking a trigeminal schwannoma with corresponding
      clinical signs. Imaging showed a left CPA lesion that was biopsied and confirmed
      as diffuse large B-cell lymphoma. Given its rarity, PCNSL should be considered in
      the differential diagnosis for all CPA tumours.

PMID- 29656001
TI  - "Flaneur neurologique in paris" - A guide to pinpointing the houses of famous
      neurologists in the late XIX century.
AB  - INTRODUCTION: During the last quarter of the XIX century, Paris, France,
      particularly the Salpetriere Hospital was the most important centre of reference
      of Clinical Neurology in the world. The group based on the Salpetriere Hospital,
      led by Professor Charcot, who was arguably the most celebrated neurologist in
      Europe. OBJECTIVE: In this historical review, we present and locate the addresses
      of the houses of these famous Parisian neurologists from the late XIX century.
      DISCUSSION: At that time, Charcot and the triumvirate of his most famous pupils,
      Pierre Marie, Joseph Babinski and Gilles de la Tourette, lived in different
      streets of Paris, predominantly in a small cluster in the districts known as 7eme
      and 8emearrondissements (7th and 8th neighbourhoods). Professor Charcot lived in
      different streets and arrondissements of Paris, including the Rue du Faubourg
      Poissonniere, Paris IX; Cite de Trevise, Paris IX; Avenue du Coq, Paris IX;
      l'Hotel de Chimay, Quai Malaquais Paris; and finally his most famous address at
      the Boulevard Saint-Germain, 217 (previously l'Hotel de Varangeville), in the
      Faubourg Saint-Germain, Paris VII. (1884). CONCLUSION: The best urban
      organization in Paris provided an interaction between Charcot and other
      privileged minds of his day. We were remembering and visiting, as a "Flaneur
      Neurologique in Paris", the addresses of the houses of these famous and
      outstanding Parisian neurologists from the late XIX century.

PMID- 29656002
TI  - Dangers of outpatient nimodipine use after spontaneous subarachnoid hemorrhage in
      accordance with the Comprehensive Stroke Center guidelines.
AB  - Despite the adverse effects and unclear benefit of the complete 21-day course of
      nimodipine therapy, The Joint Commission mandates adherence to nimodipine
      treatment for 21 days after hemorrhage or after hospital discharge if discharged
      within 21 days for Comprehensive Stroke Center (CSC) certification. We hereby
      present a 67 year-old male patient with Hunt-Hess grade 2 and Fisher grade 3 non
      aneurysmal spontaneous subarachnoid hemorrhage who was discharged with oral
      nimodipine as stipulated by the CSC guidelines, and subsequently developed
      symptomatic hypotension. This report underscores the danger of outpatient
      nimodipine use and questions the optimal length of nimodipine therapy, especially
      in patients with low risk of vasospasm. Future studies, including randomized
      controlled trials and cost-effectiveness studies, are necessary to clarify the
      benefit of 21-day nimodipine therapy compared to a shortened duration of
      nimodipine.

PMID- 29656003
TI  - Reply to the comments on effect of resveratrol on lipid profile: An updated
      systematic review and meta-analysis on randomized clinical trials.

PMID- 29656004
TI  - Comments on: "Effect of resveratrol on lipid profile: An updated systematic
      review and meta-analysis on randomized clinical trials".

PMID- 29656005
TI  - The uricosuric effects of dihydropyridine calcium channel blockers in vivo using
      urate under-excretion animal models.
AB  - The purpose of this study was to create novel urate under-excretion animal models
      using pyrazinamide and to evaluate whether dihydropyridine calcium channel
      blockers (CCBs) have uricosuric effects in vivo. Adult male ICR mice were treated
      with pyrazinamide, vehicle (dimethyl sulfoxide: DMSO), or tap water. Thirty
      minutes later, pyrazinamide-treated mice were given benzbromarone, losartan,
      nilvadipine, nitrendipine, nifedipine or azelnidipine. Six hours after the second
      administration, urine (by urinary bladder puncture) and plasma were collected to
      measure uric acid and creatinine levels, and fractional excretion of uric acid
      (FEUA) and creatinine clearance (Ccr) were calculated and evaluated. There was no
      significant difference in the levels of plasma uric acid, plasma creatinine, Ccr,
      urinary N-acetyl-beta-d-glucosaminidase (NAG) and urinary NAG-creatinine ratio
      between water, DMSO, and pyrazinamide-treated mice. But the FEUA of pyrazinamide
      treated mice was significantly lower than water mice. The FEUA was significantly
      higher in mice taking the dihydropyridine CCBs (nilvadipine, nitrendipine,
      nifedipine, and high-dose azelnidipine) than in pyrazinamide-treated mice. There
      was no significant difference in Ccr. Thus, a novel animal model created with PZA
      administration was useful as a urate under-excretion animal model that was
      probably URAT1-mediated, and the uricosuric effects of dihydropyridine CCBs were
      confirmed in vivo.

PMID- 29656006
TI  - Par-4-dependent p53 up-regulation plays a critical role in thymoquinone-induced
      cellular senescence in human malignant glioma cells.
AB  - Thymoquinone (TQ), the predominant bioactive constituent present in black cumin
      (Nigella sativa), exerts tumor suppressive activity against a wide variety of
      cancer cells. Cellular senescence, characterized by stable and long term loss of
      proliferative capacity, acts as a potent tumor suppressive mechanism. Here, we
      provide evidence for the first time that TQ suppresses growth of glioma cells by
      potentially inducing the expression of prostate apoptosis response-4 (Par-4)
      tumor suppressor protein. In turn, TQ-induced Par-4 expression triggers cellular
      senescence, as evidenced by increasing cellular size, beta-galactosidase
      staining, G1 phase arrest, and increased expression of senescence markers such as
      p53, p21, Rb, and decreased expression of lamin B1, cyclin E and cyclin depended
      kinase-2 (CDK-2). Further, overexpression of Par-4 significantly increases the
      expression of p53 and its downstream target p21, and increases beta-galactosidase
      positive cells, while siRNA/shRNA mediated-knockdown of Par-4 reverses the TQ
      induced effects. Altogether, we describe a novel mechanism of cross talk between
      Par-4 and p53, that plays a critical role in TQ-induced senescence in human
      malignant glioma cells.

PMID- 29656007
TI  - miR-195 potentiates the efficacy of microtubule-targeting agents in non-small
      cell lung cancer.
AB  - Microtubule-targeting agents (MTAs) are widely used for the treatment of non
      small cell lung cancer (NSCLC). The response rate is only ~25%, mainly
      attributable to drug resistance. To identify determinants of resistance in NSCLC,
      we performed a high-throughput screen using a library of miRNA mimics. Here we
      report that miR-195 synergizes with MTAs to inhibit the growth of NSCLC cells in
      vitro, that increased expression of miR-195 sensitizes NSCLC cells to MTAs and
      that repression of miR-195 confers resistance to MTAs. We show that NSCLC tumors
      over-expressing miR-195 are more sensitive to MTA treatment and that induced
      expression of miR-195 in NSCLC tumors potentiates the anti-tumor effect of MTAs.
      Additionally, we demonstrate that miR-195 targets checkpoint kinase 1 (CHEK1) to
      regulate the response of NSCLC cells to MTAs, that over-expression of CHEK1
      contributes to resistance to MTAs and that knock-down of CHEK1 synergizes with
      MTAs to repress cell growth. Our results highlight the importance of miR-195 in
      regulating the response of NSCLC cells to MTAs and underline the potential
      application of miR-195 as a biomarker for response to MTAs, and as a therapeutic
      adjuvant to MTA treatment.

PMID- 29656008
TI  - Identification of miRNAs linked with the drought response of tef [Eragrostis tef
      (Zucc.) Trotter].
AB  - Tef [Eragrostis tef (Zucc.) Trotter], a staple food crop in the Horn of Africa
      and particularly in Ethiopia, has several beneficial agronomical and nutritional
      properties, including waterlogging and drought tolerance. In this study, we
      performed microRNA profiling of tef using the Illumina HiSeq 2500 platform,
      analyzing both shoots and roots of two tef genotypes, one drought-tolerant
      (Tsedey) and one drought-susceptible (Alba). We obtained more than 10 million
      filtered reads for each of the 24 sequenced small cDNA libraries. Reads mapping
      to known miRNAs were more abundant in the root than shoot tissues. Thirteen and
      35 miRNAs were significantly modulated in response to drought, in Alba and Tsedey
      roots, respectively. One miRNA was upregulated under drought conditions in both
      genotypes. In shoots, nine miRNAs were modulated in common between the two
      genotypes and all showed similar trends of expression. One-hundred and forty
      seven new miRNA mature sequences were identified in silico, 22 of these were
      detected in all relevant samples and seven were differentially regulated when
      comparing drought with normal watering. Putative targets of the miRNA regulated
      under drought in root and shoot tissues were predicted. Among the targets were
      transcription factors such as CCAAT-HAP2, MADS and NAC. Verification with qRT-PCR
      revealed that five of six potential targets showed a pattern of expression that
      was consistent with the correspondent miRNA amount measured by RNA-Seq. In
      general, candidate miRNAs involved in the post-transcriptional regulation of the
      tef response to drought could be included in next-generation breeding programs.

PMID- 29656009
TI  - Omics and multi-omics approaches to study the biosynthesis of secondary
      metabolites in microorganisms.
AB  - Natural products produced by microorganisms represent the main source of
      bioactive molecules. The development of high-throughput (omics) techniques have
      importantly contributed to the renaissance of new antibiotic discovery increasing
      our understanding of complex mechanisms controlling the expression of
      biosynthetic gene clusters (BGCs) encoding secondary metabolites. In this context
      this review highlights recent progress in the use and integration of 'omics'
      approaches with focuses on genomics, transcriptomics, proteomics metabolomics
      meta-omics and combined omics as powerful strategy to discover new antibiotics.

PMID- 29656010
TI  - Age-related defects in short-term plasticity are reversed by acetyl-L-carnitine
      at the mouse calyx of Held.
AB  - Hearing acuity and sound localization are affected by aging and may contribute to
      cognitive dementias. Although loss of sensorineural conduction is well documented
      to occur with age, little is known regarding short-term synaptic plasticity in
      central auditory nuclei. Age-related changes in synaptic transmission properties
      were evaluated at the mouse calyx of Held, a sign-inverting relay synapse in the
      circuit for sound localization, in juvenile adults (1 month old) and late middle
      aged (18-21 months old) mice. Synaptic timing and short-term plasticity were
      severely disrupted in older mice. Surprisingly, acetyl-l-carnitine (ALCAR), an
      anti-inflammatory agent that facilitates mitochondrial function, fully reversed
      synaptic transmission delays and defects in short-term plasticity in aged mice to
      reflect transmission similar to that seen in juvenile adults. These findings
      support ALCAR supplementation as an adjuvant to improve short-term plasticity and
      potentially central nervous system performance in animals compromised by age
      and/or neurodegenerative disease.

PMID- 29656011
TI  - APOE genotype modifies the association between central arterial stiffening and
      cognition in older adults.
AB  - Arterial stiffening is associated with cognitive impairment and prodromal
      Alzheimer's disease. This study tested the interaction between arterial
      stiffening and an Alzheimer's disease genetic risk factor (apolipoprotein E
      [APOE] genotype) on cognition among older adults. Vanderbilt Memory & Aging
      Project participants with normal cognition (n = 162, 72 +/- 7 years, 29% APOE
      epsilon4 carrier) and mild cognitive impairment (n = 121, 73 +/- 8 years, 42%
      APOE-epsilon4 carrier) completed neuropsychological assessment and cardiac MRI to
      assess aortic stiffening using pulse wave velocity (PWV, m/s). Linear regression
      models stratified by cognitive diagnosis related aortic PWV * APOE-epsilon4
      status to neuropsychological performances, adjusting for demographic and vascular
      risk factors. PWV * APOE-epsilon4 related to poorer performance on measures of
      lexical retrieval (beta = -0.29, p = 0.01), executive function (beta = -0.44, p =
      0.02), and episodic memory (beta = -3.07, p = 0.02). Among participants with
      higher aortic PWV, APOE-epsilon4 modified the association between central
      arterial stiffening and cognition, such that carriers had worse performances than
      noncarriers. Findings add to a growing body of evidence for APOE-vascular
      interactions on cognition in older adults and warrant further research into less
      heart-healthy cohorts where the association between PWV and cognition among older
      adults might be stronger.

PMID- 29656014
TI  - And then I saw her race: Race-based expectations affect infants' word processing.
AB  - How do our expectations about speakers shape speech perception? Adults' speech
      perception is influenced by social properties of the speaker (e.g., race). When
      in development do these influences begin? In the current study, 16-month-olds
      heard familiar words produced in their native accent (e.g., "dog") and in an
      unfamiliar accent involving a vowel shift (e.g., "dag"), in the context of an
      image of either a same-race speaker or an other-race speaker. Infants'
      interpretation of the words depended on the speaker's race. For the same-race
      speaker, infants only recognized words produced in the familiar accent; for the
      other-race speaker, infants recognized both versions of the words. Two additional
      experiments showed that infants only recognized an other-race speaker's atypical
      pronunciations when they differed systematically from the native accent. These
      results provide the first evidence that expectations driven by unspoken
      properties of speakers, such as race, influence infants' speech processing.

PMID- 29656012
TI  - Muscle strength and size are associated with motor unit connectivity in aged
      mice.
AB  - In older adults, the loss of muscle strength (dynapenia) and the loss of muscle
      mass (sarcopenia) are important contributors to the loss of physical function. We
      sought to investigate dynapenia, sarcopenia, and the loss of motor unit function
      in aging mice. C57BL/6J mice were analyzed with cross-sectional (males: 3 vs. 27
      months; males and females: 8 vs. 12 vs. 20 months) and longitudinal studies
      (males: 10-25 months) using in vivo electrophysiological measures of motor unit
      connectivity (triceps surae compound muscle action potential and motor unit
      number estimation), in vivo measures of plantar flexion torque, magnetic
      resonance imaging of hind limb muscle volume, and grip strength. Compound muscle
      action potential amplitude, motor unit number estimation, and plantar flexion
      torque were decreased at 20 months. In contrast, grip strength was reduced at 24
      months. Motor unit number estimates correlated with muscle torque and hind limb
      muscle volume. Our results demonstrate that the loss of motor unit connectivity
      is an early finding in aging male and female mice and that muscle size and
      contractility are both associated with motor unit number.

PMID- 29656013
TI  - Escitalopram alleviates stress-induced Alzheimer's disease-like tau pathologies
      and cognitive deficits by reducing hypothalamic-pituitary-adrenal axis reactivity
      and insulin/GSK-3beta signal pathway activity.
AB  - Chronic stress, a causal factor for depression, can also cause cognitive
      impairments and tau pathology. However, whether and how the selective serotonin
      reuptake inhibitor antidepressant escitalopram ameliorates these effects are
      still unclear. In the present study, rats were subjected to chronic mild
      unpredictable stress for 8 weeks. Following the initial 4 weeks, the stressed
      animals were separated into susceptible (depressive) and unsusceptible
      (resistant) groups based on behavioral tests. Then, escitalopram (10 mg/kg i.p.)
      was administered for 28 days. Pathophysiological changes were assessed by
      performing behavioral and biochemical analyses. The results showed that both
      depressive and resistant rats displayed spatial memory deficits and an
      accumulation of tau in the hippocampus. Increased levels of corticosterone and
      insulin and a decreased level of glucocorticoid receptor were found in both
      depressive and resistant rats. We also found that activity-dependent
      phosphorylated insulin receptor substrate and glycogen synthase kinase-3beta
      (Ser9 site) were significantly decreased in both depressive and resistant rats.
      However, other important kinases, such as cyclin-dependent kinase 5 and mitogen
      activated protein kinase kinase-1/2, did not change in our study. Furthermore, we
      found that the mRNA expression of tau was increased in depressive and resistant
      rats. No significant change in LC3B expression was found. Interestingly, almost
      all the pathological changes in depressive and resistant rats previously
      mentioned could be reversed by escitalopram. Our results suggested that
      escitalopram ameliorates cognitive impairments and selectively attenuates
      phosphorylated tau accumulation in stressed rats through the regulation of
      hypothalamic-pituitary-adrenal axis activity and the insulin receptor
      substrate/glycogen synthase kinase-3beta signaling pathway.

PMID- 29656015
TI  - Confidence judgments during ratio comparisons reveal a Bayesian bias.
AB  - Rational numbers are essential in mathematics and decision-making but humans
      often and erroneously rely on the magnitude of the numerator or denominator to
      determine the relative size of a quotient. The source of this flawed whole number
      strategy is poorly understood. Here we test the Bayesian hypothesis that the
      human bias toward large values in the numerator or denominator of a ratio
      estimate is the result of higher confidence in large samples. Larger values are
      considered a better (more certain) instance of that ratio than the same ratio
      composed of smaller values. We collected confidence measures explicitly
      (Experiment 1) and implicitly (Experiment 2) during subjects' comparisons of non
      symbolic proportions (images with arrays of orange and blue dots). We manipulated
      the discernibility of the fractions to control difficulty and varied the
      cardinality and congruency of the numerators, denominators, and ratio values
      (e.g. 8/20 vs. 5/10 and 16/40 vs. 10/20). The results revealed that subjects'
      confidence during ratio comparisons was modulated by the numerical magnitude of
      the fraction's components, consistent with a Bayesian perception of relative
      ratios. The results suggest that the large number bias could arise from greater
      confidence in large samples.

PMID- 29656016
TI  - Riding the cell jamming boundary: Geometry, topology, and phase of human corneal
      endothelium.
AB  - It is important to assess the viability of eye-banked corneas prior to
      transplantation due to inherent senescence and known loss of endothelial cells
      during surgical manipulation. Corneal endothelial cells have a complex basal and
      paracellular shape making them challenging to accurately measure, particularly in
      oedematous ex vivo tissue. This study used calibrated centroidal Voronoi Diagrams
      to segment cells in images of these human corneas, in order to characterize
      endothelial geometry, topology, and phase. Hexagonal cells dominated the
      endothelia, with most comprised of five different pleomorphs exhibiting self
      similar topological coarsening through most of the endothelial cell density
      range. There was a linear relationship between cell size and shape, though cells
      with greater than six sides were present in larger proportions than cells with
      less. Hexagonal cell regularity was stable and largely independent of density.
      Cell and tissue phase was also examined, using the cell shape index relative to
      the recently discovered 'cell jamming' phase transition boundary. Images showed
      fluid endothelia with a range of shape indices spanning the boundary, independent
      of density but dependent on hexagonal regularity. The cells showed a bimodal
      distribution centred at the boundary, with the largest proportion of cells on the
      fluid side. A shoulder at the boundary suggested phase switching via shape
      transformation across the energy barrier, with cells either side having
      distinctly different size and shape characteristics. Regular hexagonal cells were
      closest to the boundary. This study showed the corneal endothelium acts as a
      glassy viscous foam characterized by well-established physical laws. Endothelial
      cell death transiently and locally increases cell fluidity, which is subsequently
      arrested by jamming of the pleomorphically diverse cell collective, via
      rearrangement and shape change of a small proportion of cells, which become
      locked in place by their neighbours thereby maintaining structural equilibrium
      with little energy expenditure.

PMID- 29656017
TI  - Proteomic and toxinological characterization of the venom of the South African
      Ringhals cobra Hemachatus haemachatus.
AB  - : The protein composition and toxinological profile of the venom of the African
      spitting elapid Hemachatus haemachatus (Ringhals) were characterized by bottom-up
      proteomics and functional in vitro and in vivo assays. Venom is composed of
      abundant three-finger toxins (3FTxs; 63.3%), followed by phospholipases A2
      (PLA2s; 22.8%), snake venom metalloproteinases (SVMPs; 7.1%), cysteine-rich
      secretory proteins (CRISPs; 4.1%) and Kunitz type protease inhibitors (KTPIs;
      1.5%). 3FTxs are the main responsible for lethality and myotoxicity in mice and
      in vitro anticoagulant activity. In contrast to closely related spitting species,
      whose venom 3FTxs induces dermonecrosis, the 3FTxs of H. haemachatus did not
      induce dermonecrotic activity. The venom showed in vitro PLA2 activity, and most
      likely PLA2s contribute to some extent in venom lethality, as judged by partial
      reduction in toxicity after inhibition of their catalytic activity. Despite its
      relatively high content of SVMPs, compared to most elapids, the venom of H.
      haemachatus did not exert hemorrhagic effect, proteolytic activity on azocasein
      or defibrinogenating activity. Toxicovenomic characterization of H. haemachatus
      venom revealed that RP-HPLC fractions with higher abundance of 3FTxs presented
      lethal activity, while fractions with high content of PLA2s did not, underscoring
      the role of 3FTxs in the pathophysiology caused by this venom. BIOLOGICAL
      SIGNIFICANCE: The proteomic composition and toxinological profile of the venom of
      Ringhals snake, Hemachatus haemachatus, a cobra-like spitting snake endemic to
      southern Africa, were investigated. In vitro, Ringhals venom showed anticoagulant
      and phospholipase A2 activities, but was devoid of proteolytic activity on
      azocasein. In mice, venom induced lethality and myotoxicity, but no local
      hemorrhage or dermonecrosis. The lack of dermonecrotic activity is in sharp
      contrast to venoms of closely related spitting cobras which present a similar
      relative abundance of 3FTxs but are potently dermonecrotic. 3FTxs, the most
      abundant protein family in the venom, are predominantly responsible for toxic
      effects. PLA2 enzyme inactivation experiments suggest that H. haemachatus venom
      lethality is not dependent on PLA2s, but instead is more related to neurotoxic or
      cardiotoxic 3FTxs. The characterization of this venom, based on proteomic and
      toxicovenomic approaches, is useful for more in depth studies associated with
      biogeography, phylogeny, toxinology and antivenom efficacy towards the venom of
      this species, and its association with related elapids.

PMID- 29656018
TI  - Systematic analysis of the cerebrospinal fluid proteome of fibromyalgia patients.
AB  - Fibromyalgia (FM) is a syndrome characterized by widespread muscular pain,
      fatigue and functional symptoms, which is known to be difficult to diagnose as
      the various symptoms overlap with many other conditions. Currently, there are no
      biomarkers for FM, and the diagnosis is made subjectively by the clinicians. We
      have performed shotgun proteomics on cerebrospinal fluid (CSF) from FM patients
      and non-pain controls to find potential biomarker candidates for this syndrome.
      Based on our multivariate and univariate analyses, we found that the relative
      differences in the CSF proteome between FM patients and controls were moderate.
      Four proteins, important to discriminate FM patients from non-pain controls, were
      found: Apolipoprotein C-III, Galectin-3-binding protein, Malate dehydrogenase
      cytoplasmic and the neuropeptide precursor protein ProSAAS. These proteins are
      involved in lipoprotein lipase (LPL) activity, inflammatory signaling, energy
      metabolism and neuropeptide signaling. SIGNIFICANCE: Fibromyalgia is present in
      as much as 2% of the population, causing pain, stiffness, and tenderness of the
      muscles. Upon accurate diagnostic, nonpharmacological and pharmacological
      therapies can be used to alleviate pain and manage other symptoms. However, lack
      of objective, universal applicable diagnostic criteria as well as vague and
      diffused symptoms, have made diagnosis difficult. In this context, our findings
      can shed light on potential value of CSF proteome for objectively diagnosing FM.

PMID- 29656019
TI  - Proteomic identification of virulence-related factors in young and aging C.
      elegans infected with Pseudomonas aeruginosa.
AB  - : The molecular mechanisms that distinguish immunosenescence from general age
      related decline are poorly understood. We addressed this by exposing Day 1 and
      Day 5 adults of Caenorhabditis elegans to Pseudomonas aeruginosa strain PA01, an
      opportunistic pathogen. Day 5 adult C. elegans exhibited greater vulnerability to
      infection as compared to Day 1 C. elegans. Using TMT6-plex isobaric labeling and
      reductive dimethylation, we identified 55 proteins whose levels were altered
      following infection of Day 1 and Day 5 adults. Proteins whose levels changed in
      response to infection at both ages were strongly enriched for locomotory
      functions underscoring the importance of pathogen avoidance mechanisms. In Day 1
      C. elegans, proteins with reproductive functions were highly enriched, whereas,
      Day 5 worms showed elevated levels of factors representing stress response
      pathways such as unfolded protein response (UPR) and metabolic functions. We also
      found that PA01 infection is associated with elevated protein carbonylation, an
      irreversible marker for oxidative stress. We explored the function of UNC-60, a
      cytoskeletal protein whose levels were changed by both age and infection, and
      found that mutants of unc-60 have reduced lifespan. Overall, our data provide
      novel insights into the relationship between age and immunosenescence in
      metazoans. SIGNIFICANCE: There are gaps in our knowledge pertaining to how aging
      influences an organism's response to pathogen exposure. In C. elegans, pathogen
      exposure to P. aeruginosa PA01 results in shortened lifespan, which is more
      pronounced in Day 5, compared to Day 1 adult worms. The proteome has age-specific
      responses to this exposure, and notably affects development, reproduction,
      metabolism, protein folding/unfolding, locomotion, and response to stress. This
      study addresses the molecular links between aging and immunosenescence in
      invertebrates.

PMID- 29656020
TI  - Odorant-binding protein-based identification of natural spatial repellents for
      the African malaria mosquito Anopheles gambiae.
AB  - There is increasing interest in the development of effective mosquito repellents
      of natural origin to reduce transmission of diseases such as malaria and yellow
      fever. To achieve this we have employed an in vitro competition assay involving
      odorant-binding proteins (OBPs) of the malaria mosquito, Anopheles gambiae, with
      a predominantly female expression bias to identify plant essential oils (EOs)
      containing bioactive compounds that target mosquito olfactory function. EOs and
      their fractions capable of binding to such OBPs displayed repellence against
      female mosquitoes in a laboratory repellent assay. Repellent EOs were subjected
      to gas chromatographic analysis linked to antennogram (EAG) recordings from
      female A. gambiae to identify the biologically active constituents. Among these
      compounds cumin alcohol, carvacrol, ethyl cinnamate and butyl cinnamate proved as
      effective as DEET at an equivalent dose in the repellent assay, and combinations
      of carvacrol with either butyl cinnamate or cumin alcohol proved to be
      significantly more effective than DEET in the assay. When tested as spatial
      repellents in experimental shelters housing sleeping humans in northern Nigeria a
      binary mixture of carvacrol plus cumin alcohol caused mosquitoes to leave
      shelters in significantly higher numbers to those induced by DEET in female
      Anopheles spp. and in numbers equivalent to that of DEET in Culex spp.
      mosquitoes. These findings indicate an approach for the identification of
      biologically active molecules of natural origin serving as repellents for
      mosquitoes.

PMID- 29656021
TI  - Next generation neuro-oncology.
AB  - Neuro-oncology has evolved as a growing, but still small, highly specialised and
      multidisciplinary field at the interface of several diagnostic and therapeutic
      disciplines. The major challenge in the field of primary tumours is to translate
      the almost unique progress in deciphering the highly complex molecular genetic
      nature of many primary brain tumours, notably glioblastoma, into advances that
      allow for clinical benefit for affected patients. Furthermore, metastases to the
      central nervous system are an increasingly prevalent complication in many
      systemic cancers. Their diagnosis and management require major expertise, notably
      with consideration of several new systemic therapy options, such as targeted
      therapy and immuno-oncology approaches. These new treatments contribute to
      challenges within the third major domain of neuro-oncology, the diagnosis,
      treatment and prevention of nervous system toxicity of old and new anti-cancer
      treatments. All these considerations strongly argue for the development of
      specialised centres of excellence to improve care for patients with brain tumour
      across Europe.

PMID- 29656022
TI  - Very high titres of ZnT8 autoantibodies at type 1 diabetes onset and presence of
      autoantibodies related to other autoimmune disorders.

PMID- 29656023
TI  - Impact on Dietary Choices After Discount Supermarket Opens in Low-Income
      Community.
AB  - OBJECTIVE: To examine (1) the association of a new supermarket opening with
      dietary intake and perceptions of healthy food availability, and (2) associations
      of distance to the primary food store and mean prices of fruits, vegetables, and
      sugary beverages with levels of consumption of these foods and body mass index in
      a low-income, southeastern community. METHODS: The researchers used cross
      sectional, self-administered questionnaire data and supermarket audit data
      collected in the supermarket community and comparison community before (2015) and
      after (2016) the supermarket opening. A difference-in-difference analysis
      employed propensity scores to compare pretest and posttest differences between
      communities. RESULTS: There were no significant differences between communities
      on dietary behaviors. There was a significant cross-sectional, inverse
      association between distance to the primary food store and fruit and vegetable
      consumption among all respondents in 2016. CONCLUSIONS AND IMPLICATIONS: The
      results suggest that adding a new discount supermarket is not necessarily
      associated with improvements in residents' fruit, vegetable, or sugary beverage
      consumption, or in their perceptions of the availability of healthy food in the
      neighborhood. However, distance to the store may be important.

PMID- 29656024
TI  - Protein synthesis in the basolateral amygdala complex is required for
      consolidation of a first-order fear memory, but not for consolidation of a higher
      order fear memory.
AB  - The present series of experiments pursued our recent findings that consolidation
      of a second-order fear memory requires neuronal activity, but not de novo protein
      synthesis, in the basolateral amygdala complex (BLA). It used a modified second
      order conditioning protocol in which rats were exposed to S1-shock pairings in
      stage 1 and pairings of the serial S2-S1 compound and shock in stage 2.
      Experiment 1 showed that responding (freezing) to S2 in this protocol is
      conditional on its compounding with S1 in stage 2 (Experiment 1), and therefore,
      the result of associative formation. The remaining experiments then showed that
      the protein synthesis requirement for consolidation of new learning about S2
      varied with the training afforded S1. When S1 was trained in stage 1 and present
      in stage 2, consolidation of the new S2 fear memory was unaffected by pre- or
      post-stage 2 infusions of the protein synthesis inhibitor, cycloheximide, into
      the BLA (Experiments 2 and 5). This result was observed independently of the
      number of S1-shock pairings in stage 1 (even a single pairing produced the
      result), and alongside demonstrations that cycloheximide infusions disrupt
      consolidation of a first-order fear memory (Experiments 2 and 5). However, when
      S1 was not conditioned in stage 1 (Experiment 3) or was omitted from conditioning
      in stage 2 (Experiment 4), consolidation of the new S2 fear memory was disrupted
      by post-stage 2 cycloheximide infusions into the BLA. These results were taken to
      imply that the consolidation of a higher-order fear memory exploits molecular
      events associated with consolidation of a reactivated first-order fear memory;
      hence it occurs independently of de novo protein synthesis in the BLA.
      Alternatively, the nature of the association formed in higher-order conditioning
      may be such as to not require de novo protein synthesis for its consolidation.

PMID- 29656025
TI  - Report of a consensus meeting of a group of oral and general pathologists in
      India on grading of oral epithelial dysplasia.

PMID- 29656026
TI  - Bibliometric study of articles on skeletal Class II malocclusions published in
      four high impact factor journals.
AB  - OBJECTIVE: Perform a bibliometric analysis of the orthodontic literature on
      skeletal Class II malocclusions during the first decade of the 21st century.
      MATERIALS AND METHODS: A retrospective, observational, and comprehensive study
      ranging from January the first 2001 to December 31 2010, based on the articles
      published in four high impact factor orthodontic journals: Angle Orthod, OCR,
      EJO, and AJODO (Quotation Report Newspaper of the Scientific Information
      Institute). RESULTS: In the 4565 reviewed articles, only 338 were published on
      Class II malocclusions. Brazil, the United States, Turkey, and Germany are the
      nationalities, which have published the most. The cross-sectional descriptive
      studies represent 33%, randomized clinical trials (RCTs) 10.5%, meta-analyses
      0.3%. DISCUSSION AND CONCLUSION: Kanavakis et al. (2006) reported 72.34% of
      original articles, 2.83% of synthetic reviews, 8.89% of case reports, and 15.75%
      of unclassifiable articles. In conclusion, searchers in Orthodontics are invited
      to publish more clinical trials on skeletal Class II malocclusions.

PMID- 29656027
TI  - ?

PMID- 29656028
TI  - Rice Transcription Factor OsDOF11 Modulates Sugar Transport by Promoting
      Expression of Sucrose Transporter and SWEET Genes.
AB  - Sucrose is produced in mesophyll cells and transferred into phloem cells before
      it is delivered long-distance to sink tissues. However, little is known about how
      sucrose transport is regulated in plants. Here, we identified a T-DNA insertional
      mutant of Oryza sativa DNA BINDING WITH ONE FINGER 11 (OsDOF11), which is
      expressed in the vascular cells of photosynthetic organs and in various sink
      tissues. The osdof11 mutant plants are semi-dwarf and have fewer tillers and
      smaller panicles as compared with wild-type (WT) plants. Although sucrose
      enhanced root elongation in young WT seedlings, this enhancement did not occur in
      osdof11 seedlings due to reduced sucrose uptake. Sugar transport rate analyses
      revealed that less sugar was transported in osdof11 plants than in the WT.
      Expression of four Sucrose Transporter (SUT) genes-OsSUT1, OsSUT3, OsSUT4, and
      OsSUT5-as well as two Sugars Will Eventually be Exported Transporters (SWEET)
      genes, OsSWEET11 and OsSWEET14, was altered in various organs of the mutant,
      including the leaves. Chromatin immunoprecipitation assays showed that OsDOF11
      directly binds the promoter regions of SUT1, OsSWEET11, and OsSWEET14, indicating
      that the expression of these transporters responsible for sucrose transport via
      apoplastic loading is coordinately controlled by OsDOF11. We also observed that
      osdof11 mutant plants were less susceptible to infection by Xanthomonas oryzae
      pathovar oryzae, suggesting that OsDOF11 participates in sugar distribution
      during pathogenic invasion. Collectively, these results suggest that OsDOF11
      modulates sugar transport by regulating the expression of both SUT and SWEET
      genes in rice.

PMID- 29656029
TI  - Gamma band oscillations in the early phase of psychosis: A systematic review.
AB  - Abnormal gamma oscillations, measured by electroencephalography (EEG), have been
      associated with chronic psychotic disorders, but their prevalence in the early
      phase of psychosis is less clear. We sought to address this by systematically
      reviewing the relevant literature. We searched for EEG studies of gamma band
      oscillations in subjects at high risk for psychosis and in patients with first
      episode psychosis. The following measures of gamma oscillations were extracted:
      resting power, evoked power, induced power, connectivity and peak frequency.
      Forty-five studies with a total of 3099 participants were included. There were
      potential sources of bias in the study designs and potential artefacts. Although
      there were few consistent findings, several studies reported decreased evoked or
      induced power in both high risk subjects and first episode patients. Studies
      using larger samples with serial EEG measurements, and designs that minimise
      artefacts that occur at the gamma frequency may advance work in this area.

PMID- 29656030
TI  - Post stroke depression: The sequelae of cerebral stroke.
AB  - Post-stroke depression (PSD) is the most common mental health issue, afflicting
      around 33% of stroke survivors. PSD has a negative impact on the rehabilitation,
      recuperation of motor and cognitive deficits following stroke and significantly
      increases the chances of relapsing neurovascular events. It has been demonstrated
      that biological and psychological factors have a significant role in PSD.
      Numerous endeavors have been made to discover the risk factors and predictors of
      PSD. Screening and diagnosis also have gained attention; however, a suitable tool
      is yet to be developed. Medications are chosen based on their viability and
      reaction profile in the patients. Besides pharmacotherapy, psychotherapy
      treatment is also highly valued by both psychiatrists and stroke patients.
      Additional research is needed to examine the pathophysiology of PSD. This review
      attempts to highlight the existing evidence and gaps in the present knowledge of
      the predictors of PSD, incidence, prevalence, and etiology. Further, it also
      discusses the screening and diagnostic approaches, therapeutic modalities and
      management of PSD and the impact of pre-stroke depression on PSD.

PMID- 29656031
TI  - Cerebral small vessel disease and risk of incident stroke, dementia and
      depression, and all-cause mortality: A systematic review and meta-analysis.
AB  - MRI features of cerebral small vessel disease (CSVD), i.e. white matter
      hyperintensities, lacunes, microbleeds, perivascular spaces, and cerebral
      atrophy, may be associated with clinical events, but the strength of these
      associations remains unclear. We conducted a systematic review and meta-analysis
      on the association between these features and incident ischaemic and haemorrhagic
      stroke, all-cause dementia and depression, and all-cause mortality. For the
      association with stroke, 36 studies were identified (number of individuals/events
      [n] = 38,432/4,136), for dementia 28 (n = 16,458/1,709), for depression nine (n =
      9,538/1,746), and for mortality 28 (n = 23,031/2,558). Only two studies evaluated
      perivascular spaces; these results were not pooled. Pooled analyses showed that
      all other features were associated with all outcomes (hazard ratios ranged 1.22
      2.72). Combinations of two features were more strongly associated with stroke
      than any individual feature. Individual features and combinations of CSVD
      features are strongly associated with incident ischaemic and haemorrhagic stroke,
      all-cause dementia and depression, and all-cause mortality. If these associations
      are causal, the strength of these associations suggests that a substantial burden
      of disease is attributable to CSVD.

PMID- 29656032
TI  - Bioenergetics and synaptic plasticity as potential targets for individualizing
      treatment for depression.
AB  - Disruptions of bioenergetic signaling and neurogenesis are hallmarks of
      depression physiology and are often the product of dysregulation of the
      inflammatory, stress-response, and metabolic systems. These systems are
      extensively interrelated at the physiological level, yet the bulk of the
      literature to date addresses pathophysiological mechanisms in isolation. A more
      integrated understanding of the etiology, progression, and treatment response
      profiles of depression is possible through wider consideration of relevant
      preclinical and clinical studies that examine the result of disruptions in these
      systems. Here, we review recent data demonstrating the critical effects of
      bioenergetic disruption on neuroplasticity and the development and progression of
      depressive illness. We further highlight the interactive and dynamic nature of
      the inflammatory and stress response systems and how disruption of these systems
      influences bioenergetic signaling pathways critical to treatment outcomes. In so
      doing, we underscore the pressing need to reconsider the implications of
      treatment resistance and present a framework for developing novel, personalized
      treatment approaches for depression.

PMID- 29656033
TI  - Differences in the Theory of Mind profiles of patients with anorexia nervosa and
      individuals on the autism spectrum: A meta-analytic review.
AB  - BACKGROUND: This meta-analytic review examines the theory of mind profiles in
      both patients with anorexia nervosa (AN) and autistic individuals. METHODOLOGY:
      The studies examining theory of mind were divided into the following categories:
      emotional theory of mind, understanding simple social situations, understanding
      complex social interactions, and implicit social attribution. All included
      studies investigated differences between healthy control (HCs) individuals and
      people with AN or autistic people. Differences in theory of mind profile between
      people with AN and autistic people were explored by conducting moderator
      analyses. RESULTS: People with AN and autistic people showed a similar theory of
      mind profile, but autistic individuals showed greater difficulties, particularly
      in emotional theory of mind. CONCLUSIONS: Although both people with AN and
      autistic people have significant difficulties in all aspects of theory of mind
      relative to the HCs, some differences in the underlying profile may be present.
      However, due to relative paucity of theory of mind research among people with AN,
      further research is still needed before firm conclusion can be drawn.

PMID- 29656034
TI  - Breastmilk donations: Bacteriological assessment, analysis of causes of non
      compliance and suggestions for improvement.
AB  - A total of 1099 breastmilk donations received by the milk bank at the Amiens
      University Hospital from January to June 2016 were assessed for bacteriological
      contamination according to French regulations. This consisted in enumerating the
      total aerobic flora before and after heat treatment as well as the specific
      enumeration of coagulase-positive staphylococci. Results above the mandatory
      limits for at least one of these parameters were found in 25.9% of the donations,
      resulting in the destruction of approximately one-quarter of the volume of the
      donations (~195L). This is a huge loss in both economic and health-related terms
      for neonates, especially for pre-terms. To identify ways to improve the
      bacteriological assessment results and reduce the percentage of discarded milk,
      an analysis of the causes was conducted. The two main causes of non-compliance
      were the detection of a cultivable aerobic flora after heat treatment and the
      presence of coagulase-positive staphylococci above the mandatory limit (11.7% and
      11.2% of the tested donations, respectively). Bacillus spp. were the leading
      cause of post-heat-treatment non-compliance. Therefore, the implementation of
      better environmental control could help reduce this kind of contamination. As for
      samples harboring coagulase-positive staphylococci, a further detection of toxins
      using molecular biology techniques could help discriminate actual health
      hazardous donations that have to be destroyed while enabling the use of toxin
      negative donations. Nevertheless, the economic viability of this proposal needs
      to be further assessed because these techniques are costly. Finally, a change in
      breastmilk dilutions used to enumerate the total aerobic flora to better reflect
      the actual level of these bacteria in the milk was proposed. Indeed, the
      comparison of various combinations of milk dilutions led to the conclusion that
      the association of the 1/10 and 1/100 dilutions was the best compromise between
      technical ease of enumeration and ensuring the safety of the donations.
      Implementing these suggestions would help reduce the rate of non-compliance and
      give better access to safe breastmilk donations for neonates.

PMID- 29656035
TI  - [The Artist at the hospital: A musical experience in pediatric hemodialysis].
AB  - Culture at the hospital is part of a policy of providing everyone access to
      culture. This article describes a musical intervention that provides patients and
      healthcare professionals a central role in creation; qualitatively assesses the
      benefits of these interventions for children and caregivers; evaluate the lessons
      learned from this ongoing experience in the pediatric hemodialysis unit of Rouen
      University Hospital. Ninety-minute sessions take place twice a week, with eight
      children aged from 18months to 19years, during dialysis. To assess the effects of
      artistic interventions in the unit, a qualitative methodology was chosen
      (observation grid). The progression of the project is evaluated to highlight what
      has helped the children and caregivers reach autonomy in artistic creation while
      respecting the time allotted, the artistic approach, and the esthetics of each
      participant's creation. The results indicate that this approach allows children
      to be actors, that the time at the hospital is relativized, and that the
      relationship with the healthcare professionals is less oriented towards care. A
      discussion follows on the place of the artist and the untapped potential of
      bringing patients to the creative act; the issue of esthetics, which then becomes
      secondary; the complementarity between musical activities and creation, and the
      role each actor plays in an artistic project. The hospital can provide access to
      culture; however, it is possible to go further and reveal patients' creativity.

PMID- 29656036
TI  - Laparoscopic adjustable gastric banding in adolescents with severe obesity:
      Psychological aspects, decision makers of surgery, and 2-year outcomes. A case
      series.
AB  - BACKGROUND: The results of medical treatment of severe obesity in the adolescent
      population (balanced diet and physical activity) are often unsatisfactory, and
      bariatric surgery is questioned. The psychological determinants for requesting
      bariatric surgery in these adolescents are unclear. The objective of this study
      was to report the psychiatric and psychological aspects as well as the
      determinants of the medical decision for surgery in a cohort of obese adolescents
      requesting bariatric surgery by laparoscopic adjustable gastric banding. METHODS:
      Thirty-five adolescents (12.3-17.7 years of age), were recruited from January
      2007 to December 2012. Semistructured interviews were conducted. RESULTS: Fifty
      four percent of the adolescents had a psychiatric history and 85% had psychiatric
      comorbidities. In adolescents undergoing surgery, excess weight loss was 46%
      after 1 year and 51% after 2years. For patients not receiving surgery, excess
      weight loss was 0.43% after 1 year (P=0.001). Compliance with medical treatment
      was the only significant element contributing to the decision to perform surgery.
      Results in terms of satisfaction and perception 1 and 2years after surgery were
      encouraging. CONCLUSION: Bariatric surgery is feasible in young patients and
      produces good results in terms of excess weight loss. We argue that compliance
      with medical treatment is probably one of the most important elements for making
      the decision to perform bariatric surgery and in excess weight loss after
      surgery. We probably need to focus on the compliance of young patients and
      evaluate how this can be improved.

PMID- 29656037
TI  - Prophylaxis in case of tick bite in Provence-Alpes-Cote d'Azur.

PMID- 29656038
TI  - Purpura of the chin: Two consecutive cases.
AB  - Two healthy children, a 10-year-old boy and a 13-year-old girl, both with no
      previous medical history, unrelated, presented with pinpoint purpura of the chin
      and the upper lip. It had appeared 2 days before and extended from the chin to
      the lower lip. Neither had fever or recent trauma, nor had they taken any
      medication. Their vital parameters and physical examination were normal. Their
      peripheral blood cell counts and coagulation parameters were normal. A week
      later, upon the follow-up consultation, the purpuric lesions had disappeared and
      both children reported they had played the glass game.

PMID- 29656039
TI  - Maternal adherence to guidance on breast milk collection process.
AB  - INTRODUCTION: Breast milk expression with a breast pump increases the risk of
      contaminating milk with pathogenic bacteria; how to decontaminate breast pumps is
      controversial. The aim of this study was to investigate maternal adherence to
      updated French guidance on the breast milk collection process, including breast
      pump decontamination, and to identify potential sources of increased bacterial
      counts in breast milk in order to improve prevention messages to mothers.
      METHODS: Descriptive prospective study conducted between November 2015 and April
      2016 in a French tertiary perinatal center. Oral and written instructions on the
      breast milk collection process and breast pump decontamination were given to
      mothers by trained healthcare professionals. Mothers whose neonates were admitted
      to the neonatal care unit and expressing milk for the human milk bank were
      eligible if breast milk bacterial counts before pasteurization were>=106 colony
      forming units (cfu)/mL for total aerobic flora or >=104 cfu/mL for Staphylococcus
      aureus. Maternal adherence to the guidance was investigated with a questionnaire
      and a face-to-face interview. RESULTS: One hundred and fourteen mothers with
      neonates admitted to the neonatal care unit expressed milk for the milk bank; 44
      (39%) were eligible and 29 (66%) included: most of them (76%) with increased
      counts of total aerobic flora in breast milk and 24% with increased counts of S.
      aureus. At least three divergences from the guidance provided were reported for
      16 mothers (55%). The most frequent ones were inadequate storage of the breast
      pump collection kit (62%), ineffective decontamination of the breast pump
      collection kit (52%), inappropriate cleaning of the breast pump (48%), and
      inadequate breast milk transport from home to hospital (31%). CONCLUSION: Despite
      standardized instructions, mothers with increased bacterial counts in breast milk
      frequently declared several divergences from the guidance on the breast milk
      collection process. Giving mothers and any person of their choice repeated clear
      instructions with illustrated guidance, demonstrations, and practice may help
      improve the microbiological safety of expressed breast milk.

PMID- 29656040
TI  - [Child sexual abuse: Description of a French population having consulted in a
      forensic medical service between 2011 and 2015].
AB  - BACKGROUND: When child sexual abuse (CSA) is suspected, the detection of
      anogenital anomalies is rare. In France, since 2011, most clinical examinations
      of children for whom CSA is suspected take place in the forensic medical service
      (FMS). OBJECTIVES: To describe a population of children examined for suspected
      CSA in the FMS of the Nancy Regional University Hospital Center. PATIENTS AND
      METHODS: Children under the age of 18 who consulted for suspected CSA in the
      Nancy FMS between 2011 and 2015 were included. Demographic data as well as data
      from questioning, the physical examination, any further examination, and the
      medical conclusions were collected. RESULTS: Three hundred and twenty-five girls
      and 79 boys were enrolled. The average age at the time the abuse was committed
      was 118.9 months. Two hundred sixty-nine (66.6%) children alleged fondling and 59
      (14.6%) fellatio. Two hundred twelve victims (52.5%) described a penetration, 163
      (76.9%) in the vagina and 73 (34.4%) in the anus. Significant bruises were found
      at the examination of 13 children, accounting for 2.5% of all victims. Thirty
      four (11.7%) girls had lesions in the external genitalia and 28 (9.8%) lesions of
      the virginal membrane. One boy (1.3%) had a nonspecific lesion of the external
      genitalia. Six (8.2%) children alleging anal penetrations showed injury. The
      examiner concluded that clinical examinations were compatible with alleged facts
      for 253 (62.6%) victims. It was impossible to conclude for 116 (28.7%) children.
      CONCLUSION: In the case of suspected CSA, the clinical examination is frequently
      normal. This examination must be performed by physicians trained in child abuse,
      under appropriate conditions. It is important not to jump to conclusions about
      the reality of the alleged facts. A multidisciplinary approach, with the
      cooperation of the medical, social, and forensics sector is necessary.

PMID- 29656041
TI  - Too humanlike to increase my appetite: Disposition to anthropomorphize animals
      relates to decreased meat consumption through empathic concern.
AB  - People who exclude meat from their diets are not only devoid of situational
      pressures to disengage morally and deny humanlike mental states to animals but
      also they may be dispositionally more inclined to ascribe human-like qualities to
      non-human animals than omnivores. The aim of this research was to test whether
      individual differences in anthropomorphism are related to empathic connection
      with non-human animals and hence decreased meat consumption. In two studies (N =
      588) we confirmed that decreased meat consumption was associated with both
      increased recognition of human features of animals and increased empathy to
      animals. Most importantly, our data support a model in which animals'
      anthropomorphism predicts empathy. Empathy, in turn, increases the importance
      that potential animal harm plays in dietary choices regarding meat, leading to
      reduced meat consumption.

PMID- 29656042
TI  - Detection and molecular characterization of two rare G8P[14] and G3P[3] rotavirus
      strains collected from children with acute gastroenteritis in Japan.
AB  - This study describes the detection and molecular characterization of two rare
      G8P[14] and G3P[3] rotavirus strains, which were collected from children with
      acute gastroenteritis in 2014 in Japan. Among 247 rotaviruses, one G8P[14]
      (strain 12,597) and one G3P[3] (strain 12,638) rotaviruses were detected. The
      genotypes of 11 gene segments of these two rotavirus strains (RVA/Human
      wt/JPN/12597/2014/G8P[14] and RVA/Human-wt/JPN/12638/2014/G3P[3]) were
      characterized. The genotype constellation of strain 12,597 was assigned to G8
      P[14]-I2-R2-C2-M2-A3-N2-T9-E2-H3, and this strain possessed a rare T9 genotype of
      NSP3 gene which has never been reported previously in combination with G8
      genotype of VP7 gene. Molecular characterization and phylogenetic analysis
      suggested that the strain 12,597 had the consensus G8P[14] backbone that
      originated from the rotaviruses of animal origins such as cows, deer, dogs, and
      cats. The genotype constellation of strain 12,638 was identified as G3-P[3]-I3-R3
      C3-M3-A9-N2-T3-E3-H6. The VP7 and VP4 genotypes of strain 12,638 was similar to
      those of the Cat97-like strains, but the VP1, VP2, and VP3 were closely related
      to those of the AU-1-like strain. Interestingly, the NSP1 to NSP3 genes shared
      highest identities with those of a bat rotavirus (RVA/Bat-wt/ZMB/LUS12
      14/2012/G3P[3] strain). These findings indicated that the strain 12,638 was an
      intra-genotype reassortant strain among the AU-1-like strains, the Cat97-like
      strains and the bat strain. Interestingly, the strains 12,597 and 12,638
      possessed the same N2 genotype of NSP2 gene. The results of this study support
      the possible roles of interspecies transmission and multiple reassortment events
      for generating the genetic diversity of rotavirus in human.

PMID- 29656043
TI  - Pituitary estrogen receptor alpha is involved in luteinizing hormone pulsatility
      at mid-gestation in the South American plains vizcacha, Lagostomus maximus
      (Rodentia, Caviomorpha).
AB  - The South American plains vizcacha, Lagostomus maximus, is a caviomorph rodent
      native from Argentina, Bolivia and Paraguay. It shows peculiar reproductive
      features like pre-ovulatory follicle recruitment during pregnancy with an
      ovulatory process at around mid-gestation. We have described the activation of
      the hypothalamic - pituitary - ovarian (HPO) axis during pregnancy. A progressive
      decrease of progesterone (P4) at mid-pregnancy elicits the delivery of
      gonadotropin-releasing hormone (GnRH) with the consequent secretion of follicle
      stimulating hormone (FSH) and estradiol (E2) followed by luteinizing hormone (LH)
      release resulting in follicular luteinization and the P4 concentration recover.
      Pituitary gland is the central regulator of the HPO axis being E2 a key hormone
      involved in the regulation of its activity. In this work we analyzed the action
      of E2 on the pituitary response to the GnRH wave as well as its involvement on LH
      secretion at mid-gestation in L. maximus. The expression of GnRHR at the
      pituitary pars distalis showed a significant decrease at mid-pregnancy compared
      to early- and term-gestating females. ERalpha showed a significant increment from
      mid-gestation whereas ERbeta did not show variations throughout pregnancy;
      whereas the LH expression in the pituitary pars distalis showed a significant
      increase at mid-gestation, concordantly with serum LH, which was followed by a
      decrease at term-gestation with similar values than at early-pregnancy. The
      number of cells with co-localization of ERalpha and GnRHR showed a decline at mid
      pregnancy related to early- and term-gestation, whereas the cells with co
      localization of ERalpha and LH increased at mid- and term-pregnancy. On the other
      hand, ex vivo measuring of LH pulsatility showed a significant increment in the
      total mass of LH delivered at mid-pregnancy followed by a decrease at term
      gestation. The stimulation of ERalpha with the PPT specific agonist induced a
      significant increment in the total mass of LH released, whereas no changes were
      determined when ERbeta was stimulated with its specific agonist MPP. These
      results suggest that LH pulsatility rise at mid-pregnancy would be enabled by the
      increase of E2 acting through ERalpha.

PMID- 29656044
TI  - State of the art knowledge in adrenocortical and behavioral responses to
      environmental challenges in a threatened South American ratite: Implications to
      in situ and ex-situ conservation.
AB  - The Greater Rhea (Rhea americana) is an endemic ratite to South America, whose
      wild populations have undergone a remarkable decrease due to habitat degradation
      and fragmentation by the expansion of the agricultural frontier, poaching and
      predation by dogs. Anthropogenic perturbations in wild environments, as well as
      the management in captivity, can generate different stress responses in this
      species, thus, the monitoring of adrenocortical and behavioral activities are
      considered primary assessment tools with both conservation and welfare
      implications. In this review we analyze and integrate the different measurements
      of glucocorticoids (in plasma, feces, and yolk) carried out in different captive
      and wild populations, taking into account the diverse predictable and
      unpredictable conditions to which the Greater Rhea responds in each of those
      environments. In addition, the translocation of this bird is presented as an
      application of stress physiology in field ecology for conservation purposes, in
      which we evaluated how this species responds when it is released into a novel
      environment. Our results indicate that this ratite has a striking high
      sensitivity of the hypothalamic-pituitary-adrenal (HPA) axis compared to that of
      other bird species and shows a wide variety of adrenocortical responses depending
      on the environment in which it lives. This suggests that its HPA axis has a
      phenotypic plasticity that enables the rhea to cope with the environmental
      challenges. In this sense, we propose that one of the routes of this plasticity
      could be mediated by the maternal transfer of steroid hormones to the egg.
      Finally, we discuss the importance of integrating the monitoring of the
      adrenocortical response along with the environmental variables that define the
      life history of the species, in management and conservation programs ex-situ and
      in situ.

PMID- 29656045
TI  - Distribution and morphology of gonadotropin-releasing hormone neurons in the
      hypothalamus of an induced ovulator - The llama (Lama glama).
AB  - Gonadotropin-releasing hormone (GnRH) is a decapeptide involved in the regulation
      of reproduction in all mammals, but the distribution of GnRH neurons within the
      brain varies widely among species. The objective of the present study was to
      characterize the number and distribution of GnRH neurons in the hypothalamus and
      preoptic area of llamas, an induced ovulator. The brains of female llamas (n = 4)
      were fixed, frozen and sectioned serially every 50 um in the transverse (coronal)
      plane. Every 10th section was stained for immunohistochemical detection of GnRH
      positive neuron cell bodies and fibers by incubation with 3,3'-diaminobenzidine.
      The number of counted immunoreactive cells ranged from 222 to 250 (~241 +/- 13
      cells in the preoptic area and hypothalamus per animal) and were localized in the
      medio-basal hypothalamus (44.3%), anterior hypothalamus (27%), preoptic area
      (14.9%), diagonal band of Broca/medial septum (13.4%), and mammillary area
      (0.5%). The immunoreactive cells were not localized in specific hypothalamic
      nuclei, but rather appeared to be distributed diffusely. The highest
      concentration of immunoreactive neuron fibers was in the median eminence (P <
      0.05), but fibers were identified in most of the areas analyzed, including the
      neurohypophysis. The GnRH neurons within the hypothalamus displayed monopolar
      (33%), bipolar (39%), and multipolar (28%) morphologies. The bipolar type was
      most common in the medio-basal region (40%; P < 0.05). We conclude that GnRH
      neurons and fibers form a network within the anterior and medio-basal
      hypothalamus of llamas, suggesting the central location of mechanisms controlling
      reproductive processes in llamas (i.e., induced ovulation).

PMID- 29656046
TI  - Developmental expression profiles and thyroidal regulation of cytokines during
      metamorphosis in the amphibian Xenopus laevis.
AB  - Early life-stages of amphibians rely on the innate immune system for defense
      against pathogens. While thyroid hormones (TH) are critical for metamorphosis and
      later development of the adaptive immune system, the role of TH in innate immune
      system development is less clear. An integral part of the innate immune response
      are pro-inflammatory cytokines - effector molecules that allow communication
      between components of the immune system. The objective of this study was to
      characterize the expression of key pro-inflammatory cytokines, tumor necrosis
      factor-alpha (TNFalpha), interleukin-1beta (IL-1beta) and interferon-gamma (IFN
      gamma), throughout amphibian development and determine the impacts of thyroidal
      modulation on their expression. Xenopus laevis were sampled at various stages of
      development encompassing early embryogenesis to late prometamorphosis and
      cytokine expression was measured by real-time PCR. Expression of TNFalpha and IL
      1beta were transient over development, increasing with developmental stage, while
      IFN-gamma remained relatively stable. Functionally athyroid, premetamorphic
      tadpoles were exposed to thyroxine (0.5 and 2 MUg/L) or sodium perchlorate (125
      and 500 MUg/L) for seven days. Tadpoles demonstrated characteristic responses of
      advanced development with thyroxine exposure and delayed development (although to
      a lesser extent) and increased thyroid gland area and follicular cell height with
      sodium perchlorate exposure. Exposure to thyroxine for two days resulted in
      decreased expression of IL-1beta in tadpole trunks. Sodium perchlorate had
      negligible effects on cytokine expression. Overall, these results demonstrate
      that cytokine transcript levels vary with stage of tadpole development but that
      their ontogenic regulation is not likely exclusively influenced by thyroid
      status. Understanding the direct and indirect effects of altered hormone status
      may provide insight into potential mechanisms of altered immune function during
      amphibian development.

PMID- 29656047
TI  - The complex association between metabolic syndrome and male hypogonadism.
AB  - BACKGROUND: The complex association between metabolic syndrome (MetS) and male
      hypogonadism is well established. A number of observational studies show that low
      testosterone is associated with insulin resistance and an increased risk for
      diabetes mellitus and MetS in men. AIMS: To elucidate the association between
      MetS and male hypogonadism, present epidemiological data on the co-existence of
      the two comorbidities, enlighten the underlying pathophysiology and appraise the
      effects of testosterone supplementation therapy (TTh) and lifestyle modifications
      on MetS and body composition in men. MATERIALS AND METHODS: Systematic search to
      PubMed and Medline databases for publications reporting data on association
      between MetS and male hypogonadism. RESULTS: Both MetS and male hypogonadism have
      a high prevalence in the general population and are frequently co-existing e.g.
      in males with diabetes. Accumulating evidence from animal and human studies
      suggests that MetS is involved in the pathogenesis of hypogonadism in males as
      well as the other way around. On the other hand, there is evidence for a
      favorable effect of testosterone supplementation in testosterone deficient men
      with MetS and/or diabetes mellitus. CONCLUSIONS: Studies with superior
      methodological characteristics are needed in order to establish a role for
      testosterone supplementation in men with MetS and/or diabetes mellitus.

PMID- 29656048
TI  - Trunk muscle quality assessed by computed tomography: Association with adiposity
      indices and glucose tolerance in men.
AB  - BACKGROUND/OBJECTIVES: Thigh muscle attenuation measured by computed tomography
      (CT) has been shown to be a reliable and useful index of skeletal muscle fat
      infiltration. Thigh muscle fat content assessed by CT has been linked to obesity
      and type 2 diabetes and is a correlate of insulin resistance in sedentary
      individuals. However, as measurement of mid-thigh fat content requires the
      assessment of another region of interest beyond the usual abdominal scan required
      to measure levels of visceral and subcutaneous abdominal adipose tissue, this
      study aimed at testing the hypothesis that skeletal muscle fat measured from a
      single abdominal scan (L4-L5) would also provide information relevant to the
      estimation of muscle fat infiltration as it relates to cardiometabolic risk.
      METHODS: Abdominal (L4-L5) and mid-thigh CT scans were performed in a sample of
      221 sedentary men covering a wide range of adiposity values. Trunk muscles on the
      L4-L5 scan were classified into 2 groups: 1) psoas and 2) core muscles. The two
      scans were segmented to calculate muscle areas, mean attenuation values as well
      as low-attenuation muscle (LAM) areas, the latter being considered as an index of
      skeletal muscle fat infiltration. Body mass index (BMI), body composition and
      waist circumference were assessed and a 75 g oral glucose tolerance test (OGTT)
      was performed. RESULTS: Mid-thigh, psoas and core LAM areas were all
      significantly associated with body composition indices (0.46 <= r <= 0.71, p <
      0.0001) whereas trunk muscle indices were more strongly associated with visceral
      adiposity and waist circumference (0.54 <= r <= 0.79, p < 0.0001) than were mid
      thigh muscle variables (0.44 <= r <= 0.62, p < 0.0001). Mid-thigh LAM area as
      well as psoas and core LAM areas were significantly associated with fasting
      glucose, 2-h plasma glucose levels, the glucose area under the curve and with the
      HOMA-IR index (mid-thigh LAM area: 0.18 <= r <= 0.25, p < 0.01; psoas LAM area:
      0.27 <= r <= 0.33, p < 0.0001; core LAM area: 0.24 <= r <= 0.34, p < 0.01).
      Multivariable stepwise regression analyses revealed that the associations between
      trunk muscle indices and glucose tolerance/insulin resistance were no longer
      significant after controlling for visceral adiposity measured at L4-L5.
      CONCLUSION: Our results suggest that CT-imaging derived indices of trunk muscle
      quality are related to glucose tolerance and visceral adiposity. However, the
      relationship between skeletal muscle fat and insulin resistance appears to be
      largely mediated by the concomitant variation in visceral adiposity. Finally, our
      results suggest that a single CT scan performed at L4-L5 is adequate to assess
      skeletal muscle fat content related to cardiometabolic risk.

PMID- 29656049
TI  - Reinforcing value and hypothetical behavioral economic demand for food and their
      relation to BMI.
AB  - Food is a primary reinforcer, and food reinforcement is related to obesity. The
      reinforcing value of food can be measured by establishing how hard someone will
      work to get food on progressive-ratio schedules. An alternative way to measure
      food reinforcement is a hypothetical purchase task which creates behavioral
      economic demand curves. This paper studies whether reinforcing value and
      hypothetical behavioral demand approaches are assessing the same or unique
      aspects of food reinforcement for low (LED) and high (HED) energy density foods
      using a combination of analytic approaches in females of varying BMI. Results
      showed absolute reinforcing value for LED and HED foods and relative reinforcing
      value were related to demand intensity (r's = 0.20-0.30, p's < 0.01), and demand
      elasticity (r's = 0.17-0.22, p's < 0.05). Correlations between demographic, BMI
      and restraint, disinhibition and hunger variables with the two measures of food
      reinforcement were different. Finally, the two measures provided unique
      contributions to predicting BMI. Potential reasons for differences between the
      reinforcing value and hypothetical purchase tasks were actual responding versus
      hypothetical purchasing, choice of reinforcers versus purchasing of individual
      foods in the demand task, and the differential role of effort in the two tasks.
      Examples of how a better understanding of food reinforcement may be useful to
      prevent or treat obesity are discussed, including engaging in alternative non
      food reinforcers as substitutes for food, such as crafts or socializing in a non
      food environment, and reducing the value of immediate food reinforcers by
      episodic future thinking.

PMID- 29656050
TI  - An Expanded Treatment Protocol of Panobinostat Plus Bortezomib and Dexamethasone
      in Patients With Previously Treated Myeloma.
AB  - BACKGROUND: Panobinostat was recently approved by the US Food and Drug
      Administration and European Commission in combination with bortezomib and
      dexamethasone for patients with multiple myeloma who have received >= 2 regimens,
      including bortezomib and an immunomodulatory drug. The PANEX (panobinostat
      expansion) treatment protocol provided access to panobinostat and gathered
      additional safety data before commercial availability. PATIENTS AND METHODS: In
      treatment phase 1, patients received panobinostat 20 mg 3 times per week plus
      bortezomib 1.3 mg/m2 twice weekly with dexamethasone 20 mg on the days of and
      after bortezomib treatment. Patients with no change or better in treatment phase
      1 proceeded to treatment phase 2, when bortezomib was reduced to once weekly.
      Unlike in the phase III trial, PANORAMA-1 (panobinostat or placebo with
      bortezomib and dexamethasone in patients with relapsed multiple myeloma),
      bortezomib could be administered either subcutaneously or intravenously. RESULTS:
      Thirty-nine patients with a median number of previous treatments of 4 (range, 1
      12) were enrolled; most received subcutaneous bortezomib (87%). The overall
      response rate (partial response or better) was 56%. Grade 3/4 adverse events
      included thrombocytopenia (47%), fatigue (31%), dehydration (26%), and diarrhea
      (18%). Among the patients who received subcutaneous bortezomib, relatively low
      rates of peripheral neuropathy (all grade, 15%) and notable grade 3/4 adverse
      events (thrombocytopenia, 47%; diarrhea, 12%) were observed. CONCLUSION: Overall,
      data from the PANEX trial support regulatory approval of panobinostat plus
      bortezomib and dexamethasone and suggest the potential tolerability benefits of
      subcutaneous bortezomib in this regimen.

PMID- 29656051
TI  - The private journey: An interpretative phenomenological analysis of exclusive
      breastfeeding.
AB  - BACKGROUND: Exclusive breast milk provides complete nutrition for a baby's first
      six months of life. In Australia, breastfeeding initiation rates are high,
      however duration rates are low. Although numerous studies have explored the
      reasons behind low levels of breastfeeding, few have examined the experiences of
      women who maintain exclusive breastfeeding for the recommended six-month
      duration. AIM: This paper will present an in-depth, idiographic interpretation of
      first-time mothers' experience of exclusive breastfeeding for six months in
      Australia. METHOD: Interpretative phenomenological analysis was used to explore
      how five new mothers understood their six-month exclusive breastfeeding journey.
      Face-to-face, semi-structured interviews were conducted retrospectively,
      transcribed in full, and analysed using the flexible seven-step approach of
      interpretative phenomenological analysis. FINDINGS: Three higher-order themes
      were identified: (1) exclusive breastfeeding is a personal choice, (2) exclusive
      breastfeeding is harder than expected, and (3) everyone has something to say
      about breastfeeding. CONCLUSION: The mothers were not prepared for public debates
      around infant feeding methods, where mothers judge each other and give advice
      that supports their own goals, both of which create an unnecessary divide between
      mothers. Despite these issues, the findings highlight the personal and social
      meanings aligned with exclusive breastfeeding and point to the significance in
      fostering determination as a means to achieve exclusive breastfeeding goals. This
      qualitative reflection contributes a nuanced understanding of mothers' lived
      experience of exclusive breastfeeding, deepening our understanding and enabling
      appropriate strategies and support for the longevity of exclusive breastfeeding,
      as well as direction for continued research.

PMID- 29656052
TI  - Autologous serum collected 1 h post-exercise enhances natural killer cell
      cytotoxicity.
AB  - : Natural Killer cells are cytotoxic lymphocytes that recognize and eliminate
      tumor cells. Exercise enhances NK cell cytotoxic activity (NKCA), yet the
      underlying mechanisms are not fully understood. Exercise-induced shifts in NK
      cell subsets has been proposed as one mechanism. Alternatively, exercise alters
      stress hormone and cytokine levels, which are also known to affect NKCA. AIM:
      Determine the role(s) of exercise-induced shifts in the proportions of NK-cell
      subsets found in the blood, and changes in serum IL-2, IL-6, IL-12, IFN-gamma,
      TNF-alpha and cortisol, on exercise-induced changes in NKCA. METHODS: Twelve
      adults cycled 30 min at 115% of their lactate threshold power. Peripheral blood
      mononuclear cells (PBMCs) and serum were isolated from blood collected pre-, post
      , and 1 h post-exercise. To investigate the effect of shifts in NK-cell subsets,
      pre-, post- and 1 h post-exercise NK cells were incubated with target cells (K562
      and U266) in the presence of autologous pre-exercise serum. The effects of
      hormones and cytokines released during exercise were determined by incubating pre
      exercise PBMCs with tumor target cells (K562 and U266) in the presence of pre-,
      post-, and 1 h post-exercise serum. NKCA and phenotypes were assessed by flow
      cytometry. RESULTS: Although exercise mobilized high-differentiated NK cell
      subsets (NKG2A-/KIR+), NKCA per cell was not altered post-exercise in the
      presence of pre-exercise serum. Conversely, 1 h post-exercise serum significantly
      increased the cytotoxicity of pre-exercise NK cells against HLA-expressing target
      cells (U266). This increase associated with lower levels of cortisol, and
      occurred when serum contained higher levels of IFN-gamma. CONCLUSIONS: Exercise
      induced shifts in NK-cell subsets did not fully explain changes in NKCA. Rather,
      factors present in serum during exercise recovery enhanced NKCA against target
      cells. Our results suggest lower cortisol and higher IFN-gamma levels may explain
      exercise-induced changes in NKCA.

PMID- 29656053
TI  - Novel variant NDM-11 and other NDM-1 variants in multidrug-resistant Escherichia
      coli from South India.
AB  - OBJECTIVES: Carbapenem resistance mediated by New Delhi metallo-beta-lactamase 1
      (NDM-1) and its variants has caused a major public-health concern worldwide. Here
      we report for the first time an Escherichia coli isolate positive for a novel
      variant (NDM-11). METHODS: blaNDM genes were investigated in E. coli by PCR and
      sequencing, and blaNDM variants were further characterised. The susceptibility
      pattern of novel blaNDM-11 towards different antimicrobials was compared with
      blaNDM-1 by cloning and expression in E. coli TOP10. RESULTS: A total of 33
      carbapenem-resistant E. coli isolates were screened by PCR for the presence of
      blaNDM, of which 15 (45.5%) were positive. Sequencing of the PCR products
      revealed 10 isolates with NDM-1 and 5 isolates with NDM variants (one each of NDM
      4, NDM-8 and NDM-11 and two NDM-5). Other resistance genes, including blaTEM-1,
      blaCTX-M-15, blaVIM, plasmid-encoded AmpC blaCMY-2 and 16S methyltransferases
      (rmtB and rmtC), were also associated with NDM variants in different
      combinations. The blaNDM variants were located on a transferable IncF-type
      plasmid of >100kb. Pulsed-field gel electrophoresis (PFGE) showed that all five
      E. coli isolates were unrelated, and multilocus sequence typing (MLST) revealed
      that they all belonged to ST131. Expression of the blaNDM-1 and blaNDM-11 genes
      in E. coli TOP10 showed no significant difference in MICs to various beta
      lactams, including carbapenems. CONCLUSIONS: This study underlines the spread of
      NDM variants with other antimicrobial resistance genes in E. coli in South India.
      It also describes a novel NDM variant (blaNDM-11) having an antimicrobial
      resistance pattern similar to blaNDM-1.

PMID- 29656054
TI  - Biochemical and dynamic basis for combinatorial recognition of H3R2K9me2 by dual
      domains of UHRF1.
AB  - UHRF1 is a multi-domain protein comprising of a tandem tudor (UHRF1 TTD), a PHD
      finger, and a SET and RING-associated domain. It is required for the maintenance
      of CG methylation, heterochromatin formation and DNA repair. Isothermal titration
      calorimetry binding studies of unmodified and methylated lysine histone peptides
      establish that the UHRF1 TTD binds dimethylated Lys9 on histone H3 (H3K9me2).
      Further, MD simulation and binding studies reveal that TTD-PHD of UHRF1 (UHRF1
      TTD-PHD) preferentially recognizes dimethyl-lysine status. Importantly, we show
      that Asp145 in the binding pocket determines the preferential recognition of the
      dimethyl-ammonium group of H3K9me2. Interestingly, PHD finger of the UHRF1 TTD
      PHD has a negligible contribution to the binding affinity for recognition of
      K9me2 by the UHRF1 TTD. Surprisingly, Lys4 methylation on H3 peptide has an
      insignificant effect on combinatorial recognition of R2 and K9me2 on H3 by the
      UHRF1 TTD-PHD. We propose that subtle variations of key residues at the binding
      pocket determine status specific recognition of histone methyl-lysines by the
      reader domains.

PMID- 29656056
TI  - Invited Commentary.

PMID- 29656055
TI  - Nutrient recovery from anaerobically digested chicken slurry via struvite:
      Performance optimization and interactions with heavy metals and pathogens.
AB  - The aim of this study was to assess the potential of struvite precipitation to
      recover nutrients from anaerobically-processed poultry slurry and struvite's
      interactions with heavy metals (Zn, Cu, Pb, Cr, and Ni) and pathogens (total
      coliforms and Escherichia coli). The impacts of pH, Mg, N, and P molar
      proportion, reaction time, and mixing rate and duration were explored to
      determine the optimal conditions for nutrient recovery through struvite
      precipitation. A pH range of 9.5 to 10.5, was ideal for P and N removal and
      recovery, with a molar ratio of 1:1:1 for Mg:N:P. A mixing rate of 150rpm for
      10min could allow nutrient recovery with little loss (3.32%) of NH3 through
      volatilization, and also achieve an optimal struvite crystal size (50-60MUm). The
      results of X-ray diffractometry and scanning electron microscopy confirmed that
      the precipitates generated at pH9 and 10 were orthorhombic struvite. Moreover,
      along with the recovery of nutrients, 40, 45, 66, 30, and 20% of Zn, Cu, Pb, Cr,
      and Ni, respectively, and 70% total coliforms and E. coli were removed by
      struvite precipitation from poultry slurry. This was observed despite that the
      levels of contaminants (heavy metals) detected in struvite were well below the
      permissible limits and free of pathogens. Consequently, it was inferred that the
      struvite quality was reasonable by virtue of its heavy metal and pathogen
      content, and therefore appropriate for application in the field. Similarly,
      struvite precipitation has multiple benefits as it can effectively recover
      nutrients as well as reducing pathogenic populations.

PMID- 29656057
TI  - The remarkable therapeutic potential of response-based dose individualisation in
      drug trials and patient care.
AB  - The FDA reported that most drugs are effective in only 25-62% of patients.
      Although many drugs require dose individualisation in clinical practice, dose
      finding trials usually aim to identify an optimal dose for the patient
      population. Such a dose would be suboptimal for many patients. Simulations show
      that individualised dose titration, balancing efficacy against toxicity, can
      remarkably increase the response rate - doubling it in some situations. Dose
      titration in a clinical trial can efficiently establish the realistic
      expectations for the drug's true utility in a trial setting that reflects
      clinical practice, as well as generate important knowledge to guide patient care
      through informative drug labels. This design answers key questions truly relevant
      to patient care that other designs cannot - will a patient benefit from a given
      therapy, to what extent and at what dose? Therefore, response-based dose
      titration should be considered for dose-finding trials, where appropriate, for
      drugs that will eventually be used this way in the clinic.

PMID- 29656059
TI  - Caffeic acid inhibits HCV replication via induction of IFNalpha antiviral
      response through p62-mediated Keap1/Nrf2 signaling pathway.
AB  - Hepatitis C virus (HCV) infection and its related liver disease have constituted
      a heavy burden worldwide. It had been reported that Drinking coffee could
      decrease mortality risk of HCV infected patients. Caffeic Acid (CA), the Coffee
      related organic acid could inhibit HCV replication, however, the detailed
      mechanism of CA against HCV is unclear. In this study, we showed that CA could
      notably inhibit HCV replication. Mechanism study demonstrated that CA could
      induce HO-1 expression, which would trigger the IFNalpha antiviral response, and
      the antiviral effect of CA was attenuated when HO-1 activity was inhibited by
      SnPP (an HO-1 inhibitor). CA could also increase erythroid 2-related factor 2
      (Nrf2) expression. When Nrf2 was knocked down by specific siRNA, HO-1 expression
      was concomitantly decreased while HCV expression was restored. Further study
      indicated that kelch-like ECH-associated protein 1 (keap1) expression was
      decreased by CA through p62/Sequestosome1 (p62)-mediated autophagy, which would
      lead to the stabilization and accumulation of Nrf2. The decrease of keap1 was
      restored when p62 was silenced by specific p62 siRNA and when autophagy was
      inhibited, suggesting p62-mediated autophagy was required for CA-mediated keap1
      downregulation. Taken together, the results demonstrated that CA could modulate
      Keap1/Nrf2 interaction via increasing p62 expression, leading to stabilization of
      Nrf2 and HO-1 induction, and elicit IFNalpha antiviral response to suppress HCV
      replication.

PMID- 29656058
TI  - Engaging vulnerable populations in parent-led support groups: Testing a
      recruitment strategy.
AB  - Despite the proven benefits of parenting interventions, parent engagement in such
      interventions remains low and is particularly challenging among vulnerable
      populations. This theoretically grounded study tested the effectiveness of a
      recruitment strategy - a simulated parent-led support group (PSG) - to increase
      intentions to attend a PSG in a predominantly low income, minority sample. The
      study also examined sociodemographic characteristics that may influence the
      effectiveness of the recruitment strategy and engagement in PSGs. Surveys
      assessing intentions to attend a PSG were administered before and after the
      simulation, and a 2-month follow-up survey assessed subsequent PSG attendance. A
      total of 95 participants were included in this study. Results indicate that
      participants' intentions to attend a PSG significantly increased following the
      PSG simulation (Cohen's d = 1.15), especially among Hispanics. However, PSG
      attendance in the 2 months following the PSG simulation was relatively low, with
      only 13% of parents attending a PSG or a planning meeting to start a new PSG.
      Nevertheless, this recruitment strategy may serve as an important component of a
      larger engagement effort, especially given the substantial challenges of engaging
      vulnerable populations in PSGs and other parenting interventions to reduce
      educational and health disparities.

PMID- 29656060
TI  - microRNA-96 acts as a tumor suppressor gene in human osteosarcoma via target
      regulation of EZRIN.
AB  - AIMS: microRNA-96 (miR-96) is considered as a tumor suppressor in multiple
      malignancies. Some studies have indicated that EZRIN could be regulated by the
      miR-96 in several kinds of cancer cells. However, the function of miR-96 in human
      osteosarcoma has not been investigated intensively so far. In this study, we
      mainly explored the relationship between miR-96 and the expression of EZRIN in
      human osteosarcoma cells. MAIN METHODS: The levels of miR-96 and EZRIN in
      osteosarcoma tissues and paracancerous tissues of patients were evaluated with
      qPCR. The targeted regulation between miR-96 and EZRIN was further confirmed with
      Dual luciferase assay. Overexpression of miR-96 and EZRIN was induced in human
      osteosarcoma cell line, and the changing of cell viability was analyzed to
      determine the role of miR-96 in human osteosarcoma in vitro and in vivo. KEY
      FINDINGS: Our results showed that the expression level of miR-96 was much lower
      in human osteosarcoma tissues compared with human paracancerous tissues. Dual
      luciferase assay indicated that EZRIN as the direct target of miR-96 in
      osteosarcoma cells. Besides, the up-regulation of miR-96 could inhibit cell
      proliferation, cell migration and invasion, tumor formation ability, and increase
      the percentage of cell apoptosis in osteosarcoma cells through inhibiting EZRIN.
      SIGNIFICANCE: Therefore, our study indicated that miR-96 hold an important role
      for the development and progress of human osteosarcoma, and this miRNA might
      become a novel target in the diagnosis and treatment of human osteosarcoma and
      even other cancers.

PMID- 29656061
TI  - Hypoxia-inducible bidirectional shRNA expression vector delivery using
      PEI/chitosan-TBA copolymers for colorectal Cancer gene therapy.
AB  - AIMS: This investigation was conducted to construct a hypoxia/colorectal dual
      specific bidirectional short hairpin RNA (shRNA) expression vector and to
      transfect it into the colon cancer cell line HT-29 with PEI/chitosan-TBA
      nanoparticles for the simultaneous knock down of beta-catenin and Bcl-2 under
      hypoxia. MAIN METHODS: To construct a pRNA-bipHRE-CEA vector, the carcinoma
      embryonic antigen (CEA) promoter designed in two directions and the vascular
      endothelial growth factor (VEGF) enhancer were inserted between two promoters for
      hypoxic cancer specific gene expression. To confirm the therapeutic effect of the
      dual-specific vector, beta-catenin and Bcl-2 shRNAs were inserted downstream of
      each promoter. The physicochemical properties, the cytotoxicity, and the
      transfection efficiency of these PEI/chitosan-TBA nanoparticles were
      investigated. In addition, the antitumor effects of the designed vector on the
      expression of beta-catenin and Bcl-2, cell cycle distribution, and apoptosis were
      investigated in vitro. KEY FINDINGS: The silencing effect of the hypoxia-response
      shRNA expression vector was relatively low (18%-25%) under normoxia, whereas it
      was significantly increased to approximately 50%-60% in the HT-29 cell line.
      Moreover, the cancer cells showed significant G0/G1 arrest and increased
      apoptosis due to gene silencing under hypoxia. Furthermore, MTS assay,
      fluorescence microscopy images, and flow cytometry analyses confirmed that the
      PEI/chitosan-TBA blend system provided effective transfection with low
      cytotoxicity. SIGNIFICANCE: This novel hypoxia-responsive shRNA expression vector
      may be useful for RNA interference (RNAi)-based cancer gene therapy in hypoxic
      colorectal tumors. Moreover, the PEI/chitosan-TBA copolymer might be a promising
      gene carrier for use in gene transfer in vivo.

PMID- 29656062
TI  - The impact of antibiotic prescription rates on the incidence of MRSA bloodstream
      infections: A county-level, US-wide analysis.
AB  - OBJECTIVES: To investigate the association of methicillin-resistant
      Staphylococcus aureus (MRSA) bloodstream infection with socioeconomic factors and
      antibiotic prescriptions at the county level. METHODS: MRSA bloodstream infection
      rates were extracted from the Medicare Hospital Compare database. Data on
      socioeconomic factors and antibiotic prescriptions were obtained from the US
      Census Bureau and the Medicare Part D database, respectively. RESULTS: In
      multivariate analysis, antibiotic prescriptions demonstrated a powerful positive
      association with MRSA bloodstream infection rates [Coefficient (Coeff): 0.432,
      95% Confidence Interval (CI): 0.389, 0.474, P < 0.001], which was largely
      attributable to lincosamides (Coeff: 0.257, 95% CI: 0.177, 0.336, P < 0.001),
      glycopeptides (Coeff: 0.223, 95% CI: 0.175, 0.272, P < 0.001), and sulfonamides
      (Coeff: 0.166, 95% CI: 0.082, 0.249, P < 0.001). Sociodemographic factors, such
      as poverty (Coeff: 0.094, 95% CI: 0.034, 0.155, P=0.002) exerted a secondary
      positive impact on MRSA bloodstream infection. Conversely, college education
      (Coeff: -0.037, 95% CI: -0.068, -0.005, P=0.024), a larger median room number per
      house (Coeff: -0.107, 95% CI: -0.134, -0.081, P < 0.001), and an income above the
      poverty line (100% < income < 150% of the poverty line) (Coeff: -0.257, 95% CI: 
      0.314, -0.199, P < 0.001) were negatively associated with MRSA incidence rates. A
      multivariate model that incorporated socioeconomic data and antibiotic
      prescription rates predicted 39.1% of the observed variation in MRSA bloodstream
      infection rates (Pmodel < 0.001). CONCLUSIONS: MRSA bloodstream infection rates
      were strongly associated with county-level antibiotic use and socioeconomic
      factors. If the causality of these associations is confirmed, antimicrobial
      stewardship programs that extend outside acute healthcare facilities would likely
      prove instrumental in arresting the spread of MRSA.

PMID- 29656064
TI  - A Prospective Study of Patient-reported Pain After Bulbar Urethroplasty.
AB  - OBJECTIVE: To understand the prevalence of chronic perineal pain, activity
      limitations, and patient satisfaction after urethroplasty. METHODS: From 2014 to
      2016, we prospectively enrolled men undergoing urethroplasty for bulbar urethral
      strictures. Patients, before and after surgery, completed questions from the Core
      Lower Urinary Tract Symptom Score assessing pain frequency in the bladder and
      penis or urethra, as well as nonvalidated questions assessing perineal pain.
      Overall satisfaction with their current urinary condition and pain-related
      activity limitations at home, work, or during exercise were also measured.
      Patients with <3 months of follow-up were excluded. Pre-and postoperative scores
      were compared using the Wilcoxon signed-rank test. RESULTS: Thirty-five men were
      included in the study. Mean age and body mass index were 44.6 years and 30.9
      kg/m2, respectively. Urethroplasties were anastomotic in 24 (69%) and were single
      stage buccal graft substitution in 11 (31%). Median follow-up after surgery was
      483 days (range: 90-810 days). A total of 10 patients (29%) reported worsening
      perineal pain intensity after surgery, whereas 8 (23%) reported improvement and
      17 (48%) reported no change. Overall, pain frequency in the bladder, penis or
      urethra, and perineum improved. Home and exercise pain-related activity
      restrictions improved significantly after surgery. Satisfaction with current
      urinary condition also improved with 91% reporting feeling "delighted,"
      "pleased," or "mostly satisfied" with their current condition. CONCLUSION:
      Patients are highly satisfied with their urinary condition after urethroplasty.
      Pain frequency in the bladder and the urethra significantly improves after
      urethroplasty; however, perineal pain intensity can worsen and become chronic
      after surgery in some patients.

PMID- 29656063
TI  - Updates on antibody functions in Mycobacterium tuberculosis infection and their
      relevance for developing a vaccine against tuberculosis.
AB  - A more effective vaccine to control tuberculosis (TB), a major global public
      health problem, is urgently needed. Current vaccine candidates focus
      predominantly on eliciting cell-mediated immunity but other arms of the immune
      system also contribute to protection against TB. We review here recent studies
      that enhance our current knowledge of antibody-mediated functions against
      Mycobacterium tuberculosis. These findings, which contribute to the increasing
      evidence that antibodies have a protective role against TB, include
      demonstrations that firstly distinct human antibody Fc glycosylation patterns,
      found in latent M. tuberculosis infection but not in active TB, influence the
      efficacy of the host to control M. tuberculosis infection, secondly antibody
      isotype influences human antibody functions, and thirdly that antibodies
      targeting M. tuberculosis surface antigens are protective. We discuss these
      findings in the context of TB vaccine development and highlight the need for
      further research on antibody-mediated immunity in M. tuberculosis infection.

PMID- 29656065
TI  - Penile Prosthesis in Solid Organ Transplant Recipients-A Matched Cohort Study.
AB  - OBJECTIVE: To determine whether patients with solid organ transplant (SOT) are at
      higher risk of developing complications after inflatable penile prosthesis (IPP)
      implantation. METHODS: We retrospectively reviewed outcomes data for all patients
      with SOT who underwent IPP placement at our institution. A cohort of age-matched
      IPP recipients without SOT were used as controls. RESULTS: We identified 26
      patients who underwent SOT and IPP between 1999 and 2015, and 26 controls.
      Transplants included heart (3), liver (2), kidney only (17), and kidney and
      pancreas (4). Mean follow-up time after IPP placement was 29.5 months (SOT group)
      and 13.5 months (controls). Age at IPP did not significantly differ between
      groups (53.7 + 8.1 vs 56.4 + 9.0, P = .26), nor did body mass index (30.3 + 5.5
      vs 30.2 + 4.7, P = .92), history of prostatectomy (7.7% vs 15.4%, P = .39),
      rectal surgery (3.9% vs 3.9%, P = 1.00), hyperlipidemia (69.2% vs 69.2%, P =
      1.00), hypertension (92.3% vs 76.9%, P = .25), or heart disease (57.7% vs 30.8%,
      P = .093). Peripheral vascular disease was more common in transplant patients
      (26.9% vs 3.9%, P = .021), as were stroke (19.2% vs 0.0%, P = .05) and diabetes
      (84.6% vs 53.6%, P = .016). No significant differences in IPP reoperation rates
      existed between patients with vs without SOT (11.5% vs 11.5%, P = 1.00), nor did
      they differ by organ transplanted (P = 1.00). No differences in IPP reoperation
      rate existed between 2-piece vs 3-piece IPP models (P = .47). CONCLUSION:
      Outcomes of IPP implantation in patients with SOT are similar to those of
      nontransplant patients. Patients with SOT should be considered suitable
      candidates for penile prosthesis.

PMID- 29656066
TI  - The Clinical Course of Patients With Prostate-Specific Antigen >=100 ng/ml:
      Insight Into a Potential Population for Targeted Prostate-Specific Antigen
      Screening.
AB  - OBJECTIVE: To characterize men presenting to a tertiary care safety-net hospital
      with prostate-specific antigen (PSA) values >=100 ng/mL and to identify a
      potential population for targeted PSA screening. MATERIALS AND METHODS:
      Retrospective review of 100 randomly selected patients of a total of 204 who
      presented to Grady Memorial Hospital from 2004 to 2011 with initial PSA >=100
      ng/mL was performed. Demographics, disease characteristics, and survival status
      were obtained via the Tumor Registry and a combination of electronic medical
      records and older paper charts, with missing data from paper charts excluded on
      analyses. RESULTS: Sixty-five patients were newly diagnosed with prostate cancer
      on presentation and 35 were previously diagnosed. Median PSA at presentation was
      405.5 ng/mL (minimum, 100 and maximum, 7805), 81% had metastatic disease, and 94%
      had Gleason >=7. Median Cancer of the Prostate Risk Assessment score was 8.
      Median age at presentation was 67.4 years (minimum, 40.8 and maximum, 90.6).
      Eighty-nine percent of patients were African American, 24% lived alone, 12% were
      homeless or incarcerated, 51% were insured by Medicare or Medicaid, and 47% were
      uninsured. Only 1% had human immunodeficiency virus, 19% had diabetes, and 13%
      had chronic kidney disease. Of the 65 newly diagnosed patients, only 23% had ever
      been screened and 9% were previously biopsied. Median time from presentation to
      death was 17.8 months (minimum, 0.16 and maximum, 107.1). CONCLUSION: Among men
      presenting with PSA >=100 ng/ml at a safety-net hospital, the majority were
      African American, of lower socioeconomic status, and had metastatic disease.
      Uniform absence of prostate cancer screening may expose greater numbers of at
      risk men to similar outcomes. Discussion is needed regarding targeted PSA
      screening in higher risk, vulnerable patients.

PMID- 29656067
TI  - Ternary TiO2/Fe3O4/CoWO4 nanocomposites: Novel magnetic visible-light-driven
      photocatalysts with substantially enhanced activity through p-n heterojunction.
AB  - Herein, novel magnetic TiO2/Fe3O4/CoWO4 nanocomposites were fabricated using a
      simple refluxing method followed by a calcination step at 450  degrees C.
      Photocatalytic activity of these nanocomposites were studied by decomposing
      rhodamine B, methyl orange, and fuchsine dye contaminants under visible-light
      illumination. Among the fabricated photocatalysts, the TiO2/Fe3O4/CoWO4 (30%)
      photocatalyst exhibited superior activity. The degradation rate constant for
      rhodamine B by this ternary nanocomposite was 8.5 and 5.6 folds greater than
      those of the pure TiO2 and TiO2/Fe3O4 photocatalysts, respectively. Trapping
      experiments showed that superoxide anion radicals played critical role during the
      photocatalytic process. Visible-light harvesting due to the presence of CoWO4 and
      effective suppression of the charge carriers from recombination due to formation
      of p-n heterojunction are the major parameters affecting the photocatalytic
      activity. Furthermore, the TiO2/Fe3O4/CoWO4 (30%) photocatalyst displayed highly
      stable recycling performances. The present study provides a new strategy to
      design and fabricate magnetically recoverable photocatalysts based on TiO2 with
      considerable activity under visible-light.

PMID- 29656068
TI  - Controllable fabrication of Pt nanocatalyst supported on N-doped carbon
      containing nickel nanoparticles for ethanol oxidation.
AB  - In this paper, platinum nanoparticles were deposited on a carbon carrier with the
      partly graphitized carbon and the highly dispersive carbon-coated nickel
      particles. An efficient electron transfer structure can be fabricated by
      controlling the contents of the deposited platinum. The high resolution
      transmission electron microscopy images of Pt2/Ni@CN-doped sample prove the
      electron transfer channel from Pt (1 1 1) crystal planes to graphite (1 0 0) or
      Ni (1 1 1) crystal planes due to these linked together crystal planes. The
      Pt3/Ni@CN-doped with low Pt contents cannot form the electron transfer structure
      and the Pt1/Ni@CN-doped with high Pt contents show an obvious aggregation of Pt
      nanoparticles. The electrochemical tests of all the catalysts show that the
      Pt2/Ni@CN-doped sample presents the highest catalytic activity, the strongest CO
      tolerance and the best catalytic stability. The high performance is attributed to
      the efficient electronic transport structure of the Pt2/Ni@CN-doped sample and
      the synergistic effect between Pt and Ni nanoparticles. This paper provides a
      promising method for enhancing the conductivity of electrode material.

PMID- 29656069
TI  - [Microscopic peritoneal metastases of epithelial ovarian cancers. Clinical
      relevance, diagnostic and therapeutic tools].
AB  - Understanding the biology and progression mechanisms of peritoneal metastases in
      ovarian epithelial cancers (EOC) is important because peritoneal carcinomatosis
      is present or will occur during surveillance of a majority of patients. Despite
      the clinical remission achieved after complete macroscopic cytoreductive surgery
      and platinum-based chemotherapy, 60% of patients will develop peritoneal
      recurrence. This suggests that microscopic lesions, which are not eradicated by
      surgery may be present and may participate in the mechanisms leading to
      peritoneal recurrence. This paper discusses current available data on microscopic
      peritoneal metastases, their diagnosis and their treatment. We reviewed all
      publications dealing with microscopic peritoneal metastases of EOC between 1980
      and 2017. The most recent and most relevant publications dealing with the
      treatment modalities of these metastases were selected. Peritoneal and epiploic
      microscopic localizations would occur in 1.2 to 15.1% of cases at early-stage and
      are not treated during conventional surgery. They could represent a potential
      therapeutic target. Local treatments (intraperitoneal chemotherapy, photodynamic
      therapy, fluorescence-guided surgery) seem to be necessary in addition to surgery
      and chemotherapy and may help reduce the risk of peritoneal recurrence. The place
      of these treatments in the management of EOC remains to be defined by subsequent
      researches.

PMID- 29656070
TI  - [Is universal first trimester screening for high risk of preterm preeclampsia
      clinically meaningful?]

PMID- 29656071
TI  - [Natural cycle for frozen-thawed embryo transfer: Spontaneous ovulation or
      triggering by HCG].
AB  - OBJECTIVE: To compare frozen-thawed embryo transfer (FET) outcomes in natural
      cycles according to ovulation induction: spontaneous versus recombinant human
      chorionic gonadotrophin (r-hCG) triggering. METHODS: This retrospective study
      included all patients monitored for natural cycle FET during one year. When
      serial monitoring were performed until spontaneous LH rise, patients were
      included in group A (n=38) whereas those receiving r-hCG for ovulation triggering
      formed group B (n=43). All embryos had been cryopreserved by a vitrification
      method following a previous IVF cycle. No luteal phase support had been given. We
      compared outcomes between the 2 groups. RESULTS: After checking groups
      comparability, we didn't find significant difference for the implantation rate,
      clinical pregnancy rate and live birth (31% vs 45%, 32% vs 51% et 21% vs 32%,
      respectively for group A and B). The number of monitoring was significantly lower
      in group B (1,9+/-0,8 versus 2,5+/-1, P=0,006). DISCUSSION: Although no consensus
      has been yet established, natural cycle seems indicated for normo-ovulating
      patients but the question of ovulation induction is still debated. In our study,
      triggering ovulation by r-hCG, respecting strict criteria, seems provide good
      results while reducing both protocol's constraints and cost.

PMID- 29656072
TI  - Enhanced wound healing of tissue-engineered human corneas through altered
      phosphorylation of the CREB and AKT signal transduction pathways.
AB  - : The cornea is a transparent organ, highly specialized and unique that is
      continually subjected to abrasive forces and occasional mechanical or chemical
      trauma because of its anatomical localization. Upon injury, the extracellular
      matrix (ECM) rapidly changes to promote wound healing through integrin-dependent
      activation of specific signal transduction mediators whose contribution is to
      favor faster closure of the wound by altering the adhesive and migratory
      properties of the cells surrounding the damaged area. In this study, we exploited
      the human tissue-engineered cornea (hTECs) as a model to study the signal
      transduction pathways that participate to corneal wound healing. By exploiting
      both gene profiling and activated kinases arrays, we could demonstrate the
      occurrence of important alterations in the level of expression and activation of
      a few mediators from the PI3K/Akt and CREB pathways in response to the ECM
      remodeling taking place during wound healing of damaged hTECs. Pharmacological
      inhibition of CREB with C646 considerably accelerated wound closure compared to
      controls. This process was considerably accelerated further when both C646 and
      SC79, an Akt agonist, were added together to wounded hTECs. Therefore, our study
      demonstrate that proper corneal wound healing requires the activation of Akt
      together with the inhibition of CREB and that wound healing in vitro can be
      altered by the use of pharmacological inhibitors (such as C646) or agonists (such
      as SC79) of these mediators. STATEMENT OF SIGNIFICANCE: Corneal wounds account
      for a large proportion of all visual disabilities in North America. To our
      knowledge, this is the first time that a tissue-engineered human cornea (hTEC)
      entirely produced using normal untransformed human cells is used as a biomaterial
      to study the signal transduction pathways that are critical to corneal wound
      healing. Through the use of this biomaterial, we demonstrated that human corneal
      epithelial cells engaged in wound healing reduce phosphorylation of the signal
      transduction mediator CREB while, in the mean time, they increase that of AKT. By
      increasing the activation of AKT together with a decrease in CREB activation, we
      could considerably reduce wound closure time in our punch-damaged hTECs.
      Considering the increasing interest given to the reconstruction of different
      types of tissues, we believe these results will have a strong impact on the field
      of tissue-engineering and biomaterials. Altering the activation status of the Akt
      and CREB proteins might prove to be a therapeutically interesting avenue and may
      also find applications in wound healing of other tissues beside the cornea, such
      as the skin.

PMID- 29656073
TI  - Protective therapeutic effects of peptide nanofiber and hyaluronic acid hybrid
      membrane in in vivo osteoarthritis model.
AB  - : Osteoarthritis (OA) is a condition where tissue function is lost through a
      combination of secondary inflammation and deterioration in articular cartilage.
      One of the most common causes of OA is age-related tissue impairment because of
      wear and tear due to mechanical erosion. Hyaluronic acid-based viscoelastic
      supplements have been widely used for the treatment of knee injuries. However,
      the current formulations of hyaluronic acid are unable to provide efficient
      healing and recovery. Here, a nanofiber-hyaluronic acid membrane system that was
      prepared by using a quarter of the concentration of commercially available
      hyaluronic acid supplement, Hyalgan(r), was used for the treatment of an
      osteoarthritis model, and Synvisc(r), which is another commercially available
      hyaluronic acid containing viscoelastic supplement, was used as a control. The
      results show that this system provides efficient protection of arthritic
      cartilage tissue through the preservation of cartilage morphology with reduced
      osteophyte formation, protection of the subchondral region from deterioration,
      and maintenance of cartilage specific matrix proteins in vivo. In addition, the
      hybrid nanofiber membrane enabled chondrocyte encapsulation and provided a
      suitable culturing environment for stem cell growth in vitro. Overall, our
      results suggest that this hybrid nanofibrous scaffold provides a potential
      platform the treatment of OA. STATEMENT OF SIGNIFICANCE: Osteoarthritis is a
      debilitating joint disease affecting millions of people worldwide. It occurs
      especially in knees due to aging, sport injuries or obesity. Although hyaluronic
      acid-based viscoelastic supplements are widely used, there is still no effective
      treatment method for osteoarthritis, which necessitates surgical operation as an
      only choice for severe cases. Therefore, there is an urgent need for efficient
      therapeutics. In this study, a nanofiber-HA membrane system was developed for the
      efficient protection of arthritic cartilage tissue from degeneration. This hybrid
      nanofiber system provided superior therapeutic activity at a relatively lower
      concentration of hyaluronic acid than Hyalgan(r) and Synvisc(r) gels, which are
      currently used in clinics. This work demonstrates for the first time that this
      hybrid nanofiber membrane scaffold can be utilized as a potential candidate for
      osteoarthritis treatment.

PMID- 29656074
TI  - Protein phosphatase 2A as a new target for downregulating osteoclastogenesis and
      alleviating titanium particle-induced bone resorption.
AB  - : Receptor activator of nuclear factor-kB ligand (RANKL)-induced
      osteoclastogenesis is believed to play a critical role in osteolytic diseases
      including peri-prosthetic osteolysis (PPO), the primary reason for implant
      failure and revision surgery. In this study, we observed that protein phosphatase
      2A (PP2A), a major serine-threonine phosphatase, was highly expressed in human
      periprosthetic interface membranes with aseptic loosening and in a murine
      osteolysis model induced by titanium particle irritation. PP2A inhibition
      effectively alleviated titanium particle-induced bone destruction at osteolytic
      sites. In addition, PP2A downregulation significantly decreased osteoclast
      numbers and RANKL expression, compared with in animals treated with only
      titanium. Mechanistically, a PP2A selective inhibitor or PP2A siRNA suppressed
      osteoclastogenesis and alleviated osteoclastic resorption by inhibiting the RANKL
      induced nuclear factor-kB and c-Jun N-terminal kinase signaling pathways.
      Downstream NFATc1 and c-Fos expression were also substantially suppressed by PP2A
      inhibition or knockdown. Our findings support the importance of PP2A during
      osteoclastogenesis, identifying PP2A as a novel target for treating particle
      induced or other osteoclast-mediated bone resorption diseases. STATEMENT OF
      SIGNIFICANCE: Excessive osteoclast activation disrupts bone homeostasis and leads
      to osteoclast-mediated bone resorption diseases, such as peri-prosthetic
      osteolysis, regarded as the primary reason for implant failure and revision
      surgery. Here, we firstly demonstrated protein phosphatase 2A (PP2A), a major
      serine-threonine phosphatase, was highly expressed in human periprosthetic
      interface membranes with aseptic loosening and murine osteolysis model. Moreover,
      PP2A inhibition effectively alleviated titanium particle-induced bone destruction
      and decreased osteoclast numbers. Meanwhile, a PP2A selective inhibitor or PP2A
      siRNA suppressed osteoclastogenesis and alleviated osteoclastic resorption by
      inhibiting the nuclear factor-kB and c-Jun N-terminal kinase signaling pathways.
      Thus, PP2A is involved in osteoclastogenesis and could be a promising target for
      regulating bone homeostasis and osteolytic responses.

PMID- 29656075
TI  - 3D-printed scaffolds with bioactive elements-induced photothermal effect for bone
      tumor therapy.
AB  - : For treatment of bone tumor and regeneration of bone defects, the biomaterials
      should possess the ability to kill tumor cells and regenerate bone defect
      simultaneously. To date, there are a few biomaterials possessing such dual
      functions, the disadvantages, however, such as long-term toxicity and
      degradation, restrict their application. Although bioactive elements have been
      incorporated into biomaterials to improve their osteogenic activity, there is no
      report about elements-induced functional scaffolds for photothermal tumor
      therapy. Herein, the elements (Cu, Fe, Mn, Co)-doped bioactive glass-ceramic
      (BGC) scaffolds with photothermal effect and osteogenic differentiation ability
      were prepared via 3D-printing method. Moreover, the photothermal anti-tumor
      effect and osteogenic activity of these scaffolds were systematically
      investigated. The prepared elements-doped scaffolds possessed excellent
      photothermal performance, which displayed a trend, 5Cu-BGC > 5Fe-BGC > 5Mn-BGC >
      5Co-BGC, in this study. The final temperature of elements-doped scaffolds can be
      well controlled by altering the doping element categories, contents and laser
      power density. Additionally, the hyperthermia induced by 5Cu-BGC, 5Fe-BGC and 5Mn
      BGC effectively killed tumor cells in vitro and inhibited tumor growth in vivo.
      More importantly, 5Fe-BGC and 5Mn-BGC scaffolds could promote rabbit bone
      mesenchymal stem cells (rBMSCs) adhesion, and the ionic products released from
      elements-doped scaffolds significantly stimulated the osteogenic differentiation
      of bone-forming cells. These results suggested that 5Fe-BGC and 5Mn-BGC scaffolds
      possessed promising potential for photothermal treatment of bone tumor and at the
      same time for stimulating bone regeneration, representing a smart strategy for
      the treatment of bone tumors by combining dual functional bioactive ions with
      tissue engineering scaffolds. STATEMENT OF SIGNIFICANCE: The major innovation of
      this study is that we fabricated the elements (Cu, Fe, Mn, Co)-doped bioactive
      scaffolds via 3D printing technique and found that they possess distinct
      photothermal performance and osteogenic differentiation ability. To the best of
      our knowledge, there is no report about elements-doped scaffolds for photothermal
      therapy of bone tumor. This is an important research advance by combining the
      photothermal effect and osteogenic differentiation activity of bioactive elements
      in the scaffold system for potential bone tumor therapy and bone reconstruction.
      We optimized the elements-doped scaffolds and found the photothermal effect of
      elements-doped scaffolds (5Cu-BGC, 5Fe-BGC, 5Mn-BGC) could effectively kill tumor
      cells in vivo. The photothermal performance of elements-doped scaffolds follows a
      trend: 5Cu-BGC > 5Fe-BGC > 5Mn-BGC > 5Co-BGC > BGC. Compared to traditional nano
      sized photothermal agents, bioactive elements-induced functional scaffolds have
      better biosecurity and bioactivity. Furthermore, 5Fe-BGC and 5Mn-BGC scaffolds
      displayed excellent bone-forming activity by stimulating the osteogenic
      differentiation of bone-forming cells. The major significance of the study is
      that the elements-doped bioactive glass-ceramics (5Fe-BGC, 5Mn-BGC) have great
      potential to be used as bifunctional scaffolds for photothermal tumor therapy and
      bone regeneration, representing a smart strategy for the treatment of bone tumors
      by combining dual functional bioactive ions with tissue engineering scaffolds.

PMID- 29656076
TI  - Is improved lane keeping during cognitive load caused by increased physical
      arousal or gaze concentration toward the road center?
AB  - Driver distraction is one of the main causes of motor-vehicle accidents. However,
      the impact on traffic safety of tasks that impose cognitive (non-visual)
      distraction remains debated. One particularly intriguing finding is that
      cognitive load seems to improve lane keeping performance, most often quantified
      as reduced standard deviation of lateral position (SDLP). The main competing
      hypotheses, supported by current empirical evidence, suggest that cognitive load
      improves lane keeping via either increased physical arousal, or higher gaze
      concentration toward the road center, but views are mixed regarding if, and how,
      these possible mediators influence lane keeping performance. Hence, a simulator
      study was conducted, with participants driving on a straight city road section
      whilst completing a cognitive task at different levels of difficulty. In line
      with previous studies, cognitive load led to increased physical arousal, higher
      gaze concentration toward the road center, and higher levels of micro-steering
      activity, accompanied by improved lane keeping performance. More importantly,
      during the high cognitive task, both physical arousal and gaze concentration
      changed earlier in time than micro-steering activity, which in turn changed
      earlier than lane keeping performance. In addition, our results did not show a
      significant correlation between gaze concentration and physical arousal on the
      level of individual task recordings. Based on these findings, various multilevel
      models for micro-steering activity and lane keeping performance were conducted
      and compared, and the results suggest that all of the mechanisms proposed by
      existing hypotheses could be simultaneously involved. In other words, it is
      suggested that cognitive load leads to: (i) an increase in arousal, causing
      increased micro-steering activity, which in turn improves lane keeping
      performance, and (ii) an increase in gaze concentration, causing lane keeping
      improvement through both (a) further increased micro-steering activity and (b) a
      tendency to steer toward the gaze target.

PMID- 29656077
TI  - Tumor classification with MALDI-MSI data of tissue microarrays: A case study.
AB  - With mass spectrometry imaging (MSI) on tissue microarrays (TMAs) a large number
      of biomolecules can be studied for many patients at the same time, making it an
      attractive tool for biomarker discovery. Here we investigate whether lymph node
      metastasis can be predicted from MALDI-MSI data. Measurements are performed on
      TMAs and then filtered based on spectral intensity and the percentage of tumor
      cells, after which the resulting data for 122 patients is further preprocessed.
      We assume differences between patients with and without metastasis are expressed
      in a limited number of features. Two univariate feature selection methods are
      applied to reduce the dimensionality of the MALDI-MSI data. The selected features
      are then used in combination with three classifiers. The best classification
      scores are obtained with a decision tree classifier, which classifies about 72%
      of patients correctly. Almost all the predictive power comes from a single peak
      (m/z 718.4). The sensitivity of our classification approach, which can be
      generically used to search for biomarkers, is investigated using artificially
      modified data.

PMID- 29656078
TI  - Microbial expression systems for membrane proteins.
AB  - Despite many high-profile successes, recombinant membrane protein production
      remains a technical challenge; it is still the case that many fewer membrane
      protein structures have been published than those of soluble proteins. However,
      progress is being made because empirical methods have been developed to produce
      the required quantity and quality of these challenging targets. This review
      focuses on the microbial expression systems that are a key source of recombinant
      prokaryotic and eukaryotic membrane proteins for structural studies. We provide
      an overview of the host strains, tags and promoters that, in our experience, are
      most likely to yield protein suitable for structural and functional
      characterization. We also catalogue the detergents used for solubilization and
      crystallization studies of these proteins. Here, we emphasize a combination of
      practical methods, not necessarily high-throughput, which can be implemented in
      any laboratory equipped for recombinant DNA technology and microbial cell
      culture.

PMID- 29656079
TI  - Theory and practice of using solvent paramagnetic relaxation enhancement to
      characterize protein conformational dynamics.
AB  - Paramagnetic relaxation enhancement (PRE) has been established as a powerful tool
      in NMR for investigating protein structure and dynamics. The PRE is usually
      measured with a paramagnetic probe covalently attached at a specific site of an
      otherwise diamagnetic protein. The present work provides the numerical
      formulation for probing protein structure and conformational dynamics based on
      the solvent PRE (sPRE) measurement, using two alternative approaches. An inert
      paramagnetic cosolute randomly collides with the protein, and the resulting sPRE
      manifests the relative solvent exposure of protein nuclei. To make the back
      calculated sPRE values most consistent with the observed values, the protein
      structure is either refined against the sPRE, or an ensemble of conformers is
      selected from a pre-generated library using a Monte Carlo algorithm. The ensemble
      structure comprises either N conformers of equal occupancy, or two conformers
      with different relative populations. We demonstrate the sPRE method using GB1, a
      structurally rigid protein, and calmodulin, a protein comprising two domains and
      existing in open and closed states. The sPRE can be computed with a stand-alone
      program for rapid evaluation, or with the invocation of a module in the latest
      release of the structure calculation software Xplor-NIH. As a label-free method,
      the sPRE measurement can be readily integrated with other biophysical techniques.
      The current limitations of the sPRE method are also discussed, regarding accurate
      measurement and theoretical calculation, model selection and suitable timescale.

PMID- 29656080
TI  - An NMR strategy to detect conformational differences in a protein complexed with
      highly analogous inhibitors in solution.
AB  - This manuscript presents an NMR strategy to investigate conformational
      differences in protein-inhibitor complexes, when the inhibitors tightly bind to a
      protein at sub-nanomolar dissociation constants and are highly analogous to each
      other. Using HIV-1 protease (PR), we previously evaluated amide chemical shift
      differences, DeltaCSPs, of PR bound to darunavir (DRV) compared to PR bound to
      several DRV analogue inhibitors, to investigate subtle but significant long
      distance conformation changes caused by the inhibitor's chemical moiety variation
      [Khan, S. N., Persons, J. D. Paulsen, J. L., Guerrero, M., Schiffer, C. A., Kurt
      Yilmaz, N., and Ishima, R., Biochemistry, (2018), 57, 1652-1662]. However,
      DeltaCSPs are not ideal for investigating subtle PR-inhibitor interface
      differences because intrinsic differences in the electron shielding of the
      inhibitors affect protein DeltaCSPs. NMR relaxation is also not suitable as it is
      not sensitive enough to detect small conformational differences in rigid regions
      among similar PR-inhibitor complexes. Thus, to gain insight into conformational
      differences at the inhibitor-protein interface, we recorded 15N-half filtered
      NOESY spectra of PR bound to two highly analogous inhibitors and assessed NOEs
      between PR amide protons and inhibitor protons, between PR amide protons and
      hydroxyl side chains, and between PR amide protons and water protons. We also
      verified the PR amide-water NOEs using 2D water-NOE/ROE experiments. Differences
      in water-amide proton NOE peaks, possibly due to amide-protein hydrogen bonds,
      were observed between subunit A and subunit B, and between the DRV-bound form and
      an analogous inhibitor-bound form, which may contribute to remote conformational
      changes.

PMID- 29656081
TI  - Utilizing dipole-dipole cross-correlated relaxation for the measurement of angles
      between pairs of opposing CalphaHalpha-CalphaHalpha bonds in anti-parallel beta
      sheets.
AB  - Dipole-dipole cross-correlated relaxation (CCR) between two spin pairs is rich
      with macromolecular structural and dynamic information on inter-nuclear bond
      vectors. Measurement of short range dipolar CCR rates has been demonstrated for a
      variety of inter-nuclear vector spin pairs in proteins and nucleic acids, where
      the multiple quantum coherence necessary for observing the CCR rate is created by
      through-bond scalar coupling. In principle, CCR rates can be measured for any
      pair of inter-nuclear vectors where coherence can be generated between one spin
      of each spin pair, regardless of both the distance between the two spin pairs and
      the distance of the two spins forming the multiple quantum coherence. In
      practice, however, long range CCR (lrCCR) rates are challenging to measure due to
      difficulties in linking spatially distant spin pairs. By utilizing through-space
      relaxation allowed coherence transfer (RACT), we have developed a new method for
      the measurement of lrCCR rates involving CalphaHalpha bonds on opposing anti
      parallel beta-strands. The resulting lrCCR rates are straightforward to interpret
      since only the angle between the two vectors modulates the strength of the
      interference effect. We applied our lrCCR measurement to the third immunoglobulin
      binding domain of the streptococcal protein G (GB3) and utilize published NMR
      ensembles and static NMR/X-ray structures to highlight the relationship between
      the lrCCR rates and the CalphaHalpha-CalphaHalpha inter-bond angle and bond
      mobility. Furthermore, we employ the lrCCR rates to guide the selection of sub
      ensembles from the published NMR ensembles for enhancing the structural and
      dynamic interpretation of the data. We foresee this methodology for measuring
      lrCCR rates as improving the generation of structural ensembles by providing
      highly accurate details concerning the orientation of CalphaHalpha bonds on
      opposing anti-parallel beta-strands.

PMID- 29656082
TI  - Ultra-high performance supercritical fluid chromatography hyphenated to
      atmospheric pressure chemical ionization high resolution mass spectrometry for
      the characterization of fast pyrolysis bio-oils.
AB  - Extensive characterization of complex mixtures requires the combination of
      powerful analytical techniques. A Supercritical Fluid Chromatography (SFC) method
      was previously developed, for the specific case of fast pyrolysis bio oils, as an
      alternative to gas chromatography (GC and GC * GC) or liquid chromatography (LC
      and LC * LC), both separation methods being generally used prior to mass
      spectrometry (MS) for the characterization of such complex matrices. In this
      study we investigated the potential of SFC hyphenated to high resolution mass
      spectrometry (SFC-HRMS) for this characterization using Negative ion Atmospheric
      Pressure Chemical ionization ((-)APCI) for the ionization source. The interface
      between SFC and (-)APCI/HRMS was optimized from a mix of model compounds with the
      objective of maximizing the signal to noise ratio. The main studied parameters
      included both make-up flow-rate and make-up composition. A methodology for the
      treatment of APCI/HRMS data is proposed. This latter allowed for the
      identification of molecular formulae. Both SFC-APCI/HRMS method and data
      processing method were applied to a mixture of 36 model compounds, first analyzed
      alone and then spiked in a bio-oil. In both cases, 19 compounds could be
      detected. Among them 9 could be detected in a fast pyrolysis bio-oil by targeted
      analysis. The whole procedure was applied to the characterization of a bio-oil
      using helpful representations such as mass-plots, van Krevelen diagrams and
      heteroatom class distributions. Finally the results were compared with those
      obtained with a Fourier Transform ion-cyclotron resonance mass spectrometer (FT
      ICR/MS).

PMID- 29656083
TI  - Rapid determination of 3', 4'-dimethoxy flavonol-3-beta-d-glucopyranoside in rat
      plasma by LC-MS/MS method followed by protein precipitation.
AB  - A reliable liquid chromatography/tandem mass (LC-MS/MS) method was developed for
      quantitation of 3', 4'-dimethoxy flavonol-3-beta-d-glucopyranoside (DF3G) in rat
      plasma using pantoprazole as the internal standard. An Agilent C18 column (100 mm
      * 3 mm, 3.5 MUm) was performed for chromatographic separation with the mobile
      phase composed of methanol-water (containing formic acid) at a flow rate of 0.4
      mL/min. A triple-quadrupole mass spectrometry equipped with an electrospray
      ionization (ESI) source in positive ion mode was applied to quantitative analysis
      by multiple reacting monitoring (MRM). The MRM precursor-product ion transition
      of DF3G and Pantoprazole (IS) were m/z 461.1 -> 299.2 and 383.9 -> 200.2,
      respectively. Calibration curves were recovered in a concentration range of 1-500
      ng/mL for plasma with a limit of lower quantification (LLOQ) of 1 ng/mL. The
      intra-day and inter-day precision were not >10%. The accuracy of DF3G ranged from
      -10% to 0.53% in quality control (QC) samples at three concentrations. DF3G was
      not degraded during the analysis and the storage period. All the data were
      validated in accordance with the FDA bioanalytical method validation guideline.
      The LC-MS/MS method was successfully employed in the pharmacokinetic study of the
      DF3G after oral administration and intravenous injection in rats.

PMID- 29656084
TI  - A sensitive and rapid ultra high-performance liquid chromatography with tandem
      mass spectrometric assay for the simultaneous quantitation of cyclophosphamide
      and the 4-hydroxycyclophosphamide metabolite in human plasma.
AB  - Analysis of cyclophosphamide (CP) and its metabolite, 4-hydroxycyclophosphamide
      (4OHCP), in a single assay has the ability to improve sampling techniques
      benefitting both the patients who are receiving the drug and the clinicians
      drawing samples. Due to instability in plasma (t1/2 = 4 min), immediate
      stabilization of 4OHCP with phenylhydrazine is necessary upon sample draw. After
      stabilization, 4OHCP and the stable CP prodrug concentrations can be analytically
      measured to elucidate the pharmacokinetics, including half-life and exposure
      parameters (Cmax and AUC). For this purpose, a sensitive analytical method was
      developed to measure both the prodrug and active metabolite. A liquid-liquid
      extraction recovered the analytes prior to analysis with an ultra HPLC-MS/MS. A
      Thermo ScientificTM HypersilTM BDS C18, 2.1 * 100 mm, 3.0 MUm column was used for
      compound separation. Mass transitions for CP (m/z 261.0 ? 140.0), the internal
      standard d4-CP (m/z 265.0 ? 140.0), 4OHCP (m/z 367.3 ? 147.1), and the internal
      standard AZD7451 (m/z 383.4 ? 341.1) were monitored over a calibration range of
      34.24-34,240 ng/mL and 3.424-3424 ng/mL for CP and 4OHCP, respectively. Each
      calibration range proved accurate (<15% deviation) and precise (<15% RSD) for the
      desired compound. Using this method, CP and 4OHCP plasma levels can be measured
      in clinical samples from patients receiving this therapy.

PMID- 29656085
TI  - Validated HPTLC method for determination of ledol and alloaromadendrene in the
      essential oil fractions of Rhododendron tomentosum plants and in vitro cultures
      and bioautography for their activity screening.

PMID- 29656086
TI  - HIV-1 non-R5 tropism correlates with a larger size of the cellular viral
      reservoir and a detectable residual viremia in patients under suppressive ART.
AB  - BACKGROUND: The influence of HIV-1 co-receptor usage on the course of therapy in
      subjects fully responding to ART has been poorly investigated. OBJECTIVES: To
      explore the relationship between co-receptor tropism and cellular reservoir size,
      residual viremia and subsequent virological outcome in ART-treated patients with
      HIV-1 RNA stable <50 copies/mL. STUDY DESIGN: Viral co-receptor usage was
      predicted by viral env DNA sequencing with geno2pheno interpretation (FPR20%) and
      classified as R5 and non-R5. Total blood-associated HIV-1 DNA levels (log10
      copies/106 leukocytes) were measured by qRT-PCR (5'LTR). Residual plasma viremia
      was categorized as detectable (1-49 cps/mL) or undetectable (<1 copy/mL).
      Virological rebounds (any HIV-1 RNA >50 copies/mL) were evaluated over 96 weeks.
      RESULTS: The study included 116 subjects. Patients with R5 virus (n = 59) and non
      R5 virus (n = 57) were homogeneous for the main characteristics except for the
      lower nadir CD4 cell count in the non-R5 group. Patients with non-R5 variants
      showed higher levels of HIV-1 DNA as compared to patients with R5 virus: mean
      2.47 (95% CI 2.37-2.56) vs 2.17 (2.08-2.26) (p < 0.001). Moreover, a higher
      proportion of patients in the non-R5 group displayed detectable residual viremia
      with respect to the R5-group (54.4% vs 32.2%, p = .016). Detectable residual
      viremia was found to be significantly associated with viral rebounds. CONCLUSION:
      The presence of non-R5 viral DNA variants is related to a higher probability of
      residual viremia and to a larger size of the cellular viral reservoir in this
      setting. These data highlight a potential role of viral tropism in the monitoring
      of HIV-1 infection in virologically controlled subject.

PMID- 29656087
TI  - Molecular features of Hepatitis E Virus circulation in environmental and human
      samples.
AB  - BACKGROUND AND OBJECTIVES: Hepatitis E virus (HEV) is emerging but its
      circulation between humans and the environment remains misunderstood. HEV ORF2
      gene encodes the capsid playing a key role in viral interactions with surfaces,
      ORF3 products are involved in the viral cycle. Our aim was to study the molecular
      characteristics of ORF2 and ORF3 which could favor HEV fitness in patients and
      the environment. STUDY DESIGN: Samples from 69 patients with hepatitis
      (blood/stools), 20 urban wastewaters, 20 effluents of a pig slaughterhouse, 22
      farm pigs (stools), 20 wild boars (liver/stools) were collected in North-Eastern
      France. HEV strains were analyzed by direct sequencing within the ORF2 M region,
      of ORF2/ORF3, for phylogeny and physicochemical prediction and for ORF2 by ultra
      deep sequencing. RESULTS: The results showed frequent HEV-positive samples: 9.1%
      of the patient bloods, 23.1% of their stools; 25.0% of wastewaters, 75.0% for the
      slaughterhouse, 10.0% of the boar livers, 5.3% of their stools. The strains were
      classified as HEV genotype 3. In ORF2, HEV highlighted one homogeneous major
      viral variant within quasispecies and a decrease in predicted antigenicity for
      two minor mutations (D442G, V402A). A cysteine signature at position 81 in ORF3
      was observed in the boars. CONCLUSIONS: HEV RNA genotype 3 was detected in
      patients and in animals, in a slaughterhouse effluent and in wastewater.
      Moreover, the low variability of amino acids in the ORF2 M region and molecular
      features in ORF2 and ORF3 suggested that HEV strains could be advantageous for
      key properties.

PMID- 29656088
TI  - "Ne nnipadua mmpe" (the body hates it): Exploring the lived experience of food
      allergy in Sub-Saharan Africa.
AB  - Allergic diseases have closely followed the rise of non-communicable diseases
      (NCDs) especially in western societies. As prevalence of NCD is increasing in sub
      Saharan Africa (SSA), researchers are hinting that the same future may hold for
      (food) allergic disease in this world region. Already, researchers are beginning
      to record prevalence, though with little attention to the social experience of
      individuals and parents with food allergic children. This paper presents the
      first qualitative analysis of the daily realities of adults and parents of
      children with allergies in SSA using Ghana as a case study. Drawing on political
      ecology of health, this study contextualizes the psychological (e.g. anxiety and
      fear), social (e.g. stigmatization, social exclusion), and economic (e.g. impact
      on work & household expenditures) wellbeing of affected persons within the
      broader sociocultural environment. By exploring the sociocultural environment,
      the results provide insights into the likely structures (e.g. the lack of
      familiarity, absence of local discursive repertoire on food allergy,
      infrastructure deficit) which interact to shape anxiety, and social exclusion of
      people with allergy. The case study provides evidence suggesting food allergies
      do have a global reach, and policy makers must heed the message to integrate food
      allergy into the broader chronic disease prevention agenda.

PMID- 29656089
TI  - Microbiology catches the cryo-EM bug.
AB  - Over the past few years, the advances in technology and methods that have
      revolutionized cryo-EM are allowing for key insights in a variety of areas in
      biology, and microbiology is no exception. A wide range of important
      macromolecular assemblies in prokaryotic and eukaryotic cells, as well as intact
      viruses, have now become accessible to investigation by new methods in 3D
      electron microscopy. We focus here on selected examples that illustrate this
      breadth, and review the application of methods in single particle cryo-EM and
      cryo-electron tomography to progress in the structural biology of CRISPR systems,
      visualization of small molecule drugs in membrane proteins, in situ visualization
      of bacterial nanomachines, and the analysis of antigen-antibody interactions to
      drive vaccine design.

PMID- 29656090
TI  - Naturally occurring compounds in differentiation based therapy of cancer.
AB  - Differentiation of cancer cells entails the reversion of phenotype from malignant
      to the original. The conversion to cell type characteristic for another tissue is
      named transdifferentiation. Differentiation/transdifferentiation of malignant
      cells in high grade tumor mass could serve as a nonaggressive approach that
      potentially limits tumor progression and augments chemosensitivity. While this
      therapeutic strategy is already being used for treatment of hematological
      cancers, its feasibility for solid malignancies is still debated. We will
      presently discuss the natural compounds that show these properties, with focus on
      anthraquinones from Aloe vera, Senna, Rheum sp. and hop derived prenylflavonoids.

PMID- 29656091
TI  - Serial reversal learning and cognitive flexibility in two species of Neotropical
      parrots (Diopsittaca nobilis and Pionites melanocephala).
AB  - Serial reversal learning of colour discriminations was assessed as an index of
      cognitive flexibility in two captive species of Neotropical parrots. Both species
      showed similar performances across serial reversals and no between species
      differences were observed. In a second task subjects' performances were assessed
      after they experienced either a low or high pre-reversal learning criterion. If
      reversal performances improve through processes of associative learning, a high
      pre-reversal criterion is expected to strengthen previously learned associations
      and hence impede post-reversal performances. Conversely, highly reinforced
      associations may facilitate the use of conditional rules that can be generalised
      across reversals and improve post-reversal performances. We found that high
      criterion subjects made fewer post-reversal errors and required fewer trials to
      reach criterion, than low criterion subjects. Red-shouldered macaws and black
      headed caiques may therefore demonstrate capacities for solving serial reversal
      problems by applying conditional rules, rather than learning solely by
      associative processes. Such performances coincide with findings in great apes,
      but contrast with findings in monkeys and prosimians, which generally show
      impaired reversal performances when trained to a highly rigorous pre-reversal
      criterion. Overall, these findings suggest an evolutionary convergence of
      cognitive flexibility between parrots and non-human great apes.

PMID- 29656092
TI  - Sleep deprivation impairs cognitive performance in zebrafish: A matter of fact?
AB  - The zebrafish (Danio rerio) has become a valuable model organism for behavioral
      studies examining learning and memory. Its diurnal circadian rhythm and
      characterized sleep-like state make it comparable to mammals, features that have
      contributed to establishing this small vertebrate as a translational model for
      sleep research. Despite sleep being an evolutionarily conserved behavior, its
      mechanisms and functions are still debated. Sleep deprivation is commonly
      associated with decreased attention, reduced responsiveness to external stimuli,
      altered locomotor activity and impaired performance on cognitive tasks. In the
      current study, we examined the effects of partial and total sleep deprivation on
      zebrafish learning performance in an active avoidance conditioning paradigm. In
      addition, we examined the effects of two drugs known to alter sleep (alcohol and
      melatonin) on learning performance in sleep deprived animals. Our results suggest
      that although partial sleep deprivation did not alter learning performance, total
      sleep deprivation was found to significantly impair behavioral responses to the
      electric shock as well as avoidance learning. However, when sleep deprived fish
      were treated with alcohol the night before the learning task, learning
      performance was similar to the control group. In contrast, melatonin treatment
      did not alter learning performance in sleep deprived animals. We conclude that
      the zebrafish is a sensitive tool for investigating the effects of sleep
      deprivation on cognitive performance and may be a useful model for dissecting the
      mechanisms underlying learning and memory.

PMID- 29656093
TI  - The role of singing style in song adjustments to fluctuating sound conditions: A
      comparative study on Mexican birds.
AB  - Many bird species adjust their songs to noisy urban conditions by which they
      reduce masking and counteract the detrimental impact on signal efficiency.
      Different species vary in their response to level fluctuations of ambient noise,
      but it remains unclear why they vary. Here, we investigated whether noise
      dependent flexibility may relate to singing style and signal function of the
      flexible acoustic trait. Species with highly variable songs may generally be more
      flexible and strongly repetitive singers may be more limited to stray from their
      stringent patterns. We exposed males of four passerine species with contrasting
      singing styles (repertoire size, immediate or eventual variety singing and
      syllable diversity) to three experimental sound conditions: 1) continuous urban
      noise; 2) intermittent white noise and 3) conspecific song playback. We found no
      spectral or temporal changes in response to experimental noise exposure in any of
      the four species, but significant temporal adjustment to conspecific playback in
      one of them. We argue that the consistency in song frequency and timing may have
      signal value, independent of singing style, and therefore be an explanation for
      the general lack of noise-dependent flexibility in the four species of the
      current study.

PMID- 29656094
TI  - Social interaction with a tutor modulates responsiveness of specific auditory
      neurons in juvenile zebra finches.
AB  - Behavioral states of animals, such as observing the behavior of a conspecific,
      modify signal perception and/or sensations that influence state-dependent higher
      cognitive behavior, such as learning. Recent studies have shown that neuronal
      responsiveness to sensory signals is modified when animals are engaged in social
      interactions with others or in locomotor activities. However, how these changes
      produce state-dependent differences in higher cognitive function is still largely
      unknown. Zebra finches, which have served as the premier songbird model, learn to
      sing from early auditory experiences with tutors. They also learn from playback
      of recorded songs however, learning can be greatly improved when song models are
      provided through social communication with tutors (Eales, 1989; Chen et al.,
      2016). Recently we found a subset of neurons in the higher-level auditory cortex
      of juvenile zebra finches that exhibit highly selective auditory responses to the
      tutor song after song learning, suggesting an auditory memory trace of the tutor
      song (Yanagihara and Yazaki-Sugiyama, 2016). Here we show that auditory responses
      of these selective neurons became greater when juveniles were paired with their
      tutors, while responses of non-selective neurons did not change. These results
      suggest that social interaction modulates cortical activity and might function in
      state-dependent song learning.

PMID- 29656095
TI  - A protocol of human animal interaction to habituate young sheep and goats for
      behavioural studies.
AB  - Animal habituation is key to obtain reliable data on behavioural studies but
      detailed procedures to achieve it are scarce. This study designed a set of
      actions to habituate sheep and goats to human observers. Pelibuey sheep (n = 15)
      and Criollo goats (n = 10) were classified as (a) avoider, flight from human
      interaction, or (b) follower, seek human interaction. Habituation was measured by
      the reduction of flight distance by avoiders, or number of followers in the
      presence of observers. The habituation protocol consisted of a gradually
      increased series of five manoeuvres, either challenge (for avoiders) or evasion
      (for seekers), performed first inside a pen and subsequently in a grass paddock.
      Habituation was considered successful when animals could be observed from a 1-m
      distance without flight or following the observer. In the pen, habituation took
      12 and 13 days for sheep and goats, respectively. Meanwhile, in the grass paddock
      habituation took 10 days, for both species. The number of challenge and evasion
      series was negatively correlated with the flight distance in sheep and with the
      number of followers in goats. This protocol is simple and practical to implement
      and enables animal habituation for behavioural studies.

PMID- 29656096
TI  - The influence of exercise on anxiety-like behavior in zebrafish (Danio rerio).
AB  - In non-human mammals, exercise has been shown to decrease anxiety-like behavior.
      Conversely, a number of studies have reported no effect or even an increase in
      anxiety-like behavior after exercise, however, inconsistent training regimes and
      behavioral paradigms across studies may be confounding the results. Zebrafish
      (Danio rerio) are a well-established animal model in neurobehavioral research,
      and have the potential to shed new insight into the effects of exercise on
      anxiety-like behavior where previous research has been limited, due to the
      ability to precisely control intensity and duration of exercise, and the
      validation of tests for measuring different aspects of anxiety-like behaviors. In
      the current study, fish were split between two treatment groups; Exercised and
      Control. Fish in the exercised condition were aerobically challenged (max water
      velocity: 0.5 m/s) using a swim tunnel one hour a day, five days a week, for six
      weeks. Control fish spent an equal amount of time in the swim tunnel but were not
      aerobically challenged (max water velocity: 0.05 m/s). After six weeks, all fish
      were tested individually in two standard complimentary anxiety tests for
      zebrafish: the novel tank test and the light-dark test. Exercised fish exhibited
      reduced anxiety-like behaviors in the novel tank test; they spent more time in
      the top and were quicker to enter the top of a novel tank compared to Control
      fish. In addition, Exercised fish spent more time in the light compartment of the
      light-dark test compared to Control fish. Our results demonstrate the beneficial
      effect of exercise on anxiety-like behavior in zebrafish.

PMID- 29656097
TI  - Treatment of epilepsy in multiple sclerosis.
AB  - PURPOSE: The prevalence of epilepsy is increased in multiple sclerosis (MS), but
      information on AED treatment and seizure outcome is scarce. We describe epilepsy
      characteristics including the use of AEDs and proportion of seizure-free patients
      at two tertiary hospitals in Sweden. METHOD: We retrospectively studied
      electronic medical records of all patients with a diagnosis of MS and seizures at
      Sahlgrenska university hospital and Uppsala university hospital. Clinical data
      were reviewed until 2017. RESULTS: We identified a total of 62 MS patients with
      at least one seizure. Median age at the first seizure (before or after MS) was 41
      years (range 0-80). The most common MS disease course at the first seizure was
      secondary progressive MS, the neurological disability was considerable, and most
      patients had several MRI lesions at their first seizure. The first EEG
      demonstrated epileptiform discharges in 38% and unspecific pathology in 40%.
      Current seizure status could be determined for 37 patients. Out of these, 46% had
      been seizure free for more than one year at last follow-up. The majority of
      patients (65%) were on monotherapy at last follow-up. Carbamazepine was the most
      commonly used first AED, with a retention rate of 52%. No individual AED was
      associated with a particularly high rate of seizure freedom. The most common
      reason for discontinuation of the first AED was side-effects. CONCLUSION: Seizure
      freedom rates were low, perhaps indicating a need for higher ambitions in
      management. Side effects of AEDs may be a particular concern when treating
      epilepsy in patients with MS.

PMID- 29656098
TI  - A novel PIGA mutation in a Taiwanese family with early-onset epileptic
      encephalopathy.
AB  - PURPOSE: We report the first family with PIGA-associated epileptic encephalopathy
      in Taiwan and hope to elucidate its special phenotype and inheritance pattern.
      METHOD: We found a Taiwanese family with several members suffered from severe
      epileptic encephalopathy (ZY07, ZY01, ZY04). To determine the underlying
      etiology, whole exome sequencing was conducted. RESULTS: A single novel variant,
      NM_002641: c.356G > A, p.Arg119Gln, was identified in the X chromosome PIGA gene
      in our proband patient (ZY07). The patient's mother (ZY02) and aunt (ZY03) were
      confirmed as carriers of the hemizygous variant. CONCLUSIONS: This paper
      highlights the highly transmitted features of PIGA and other X-linked EIEEs,
      raising awareness of rare forms of epileptic encephalopathy.

PMID- 29656099
TI  - Hypsarrhythmia in epileptic spasms: Synchrony in chaos.
AB  - PURPOSE: Hypsarrhythmia is an electroencephalographic pattern associated with
      epileptic spasms and West syndrome. West syndrome is a devastating epileptic
      encephalopathy, originating in infancy. Hypsarrhythmia has been deemed to be the
      interictal brain activity, while the electrodecremental event associated with the
      spasms is denoted as the ictal event. Though characterized as chaotic,
      asynchronous and disorganized based on visual inspection of the EEG, little is
      known of the dynamics of hypsarrhythmia and how it impacts the developmental
      arrest of these infants. METHODS: As an exploratory and feasibility study, we
      explored the dynamics of both hypsarrhythmia and electrodecremental events with
      EEG phase synchronization methods, and in a convenience sample of three
      outpatients with epileptic spasms. As ictal events are associated with prolonged
      phase synchronization, we hypothesized that if hypsarrhythmia was indeed the
      interictal brain activity that it would have lower phase synchronization than the
      electrodecremental event (ictal phase). RESULTS: We calculated both the phase
      synchronization index and the temporal variability of the index in three patients
      with infantile spasms. Two patients had hypsarrhythmia and electrodecremental
      events and one had hemi-hypsarrhythmia. We found that the hypsarrhythmia pattern
      was a more synchronized state than the electrodecremental event. CONCLUSIONS: We
      have observed that the hypsarrhythmia pattern may represent a more synchronized
      state than the electrodecremental event in infants with epileptic spasms.
      However, larger studies are needed to replicate and validate these findings.
      Additionally, further inquiry is required to determine the impact that increased
      synchronization may have on developmental outcomes in infants with epileptic
      spasms.

PMID- 29656100
TI  - Extracellular activity of NBAD-synthase is responsible for colouration of brown
      spots in Ceratitis capitata wings.
AB  - After the emergence of the Ceratitis capitata imago, the pale and folded wings
      are expanded and sclerotized to acquire the definitive form and to stabilize the
      cuticle. The wings of this fly show a specific pattern of brownish and black
      spots. Black spots are pigmented by melanin, whereas there was scarce information
      about the development of the brownish spots. N-beta-alanydopamine (NBAD) is the
      main tanning precursor in C. capitata body cuticle, and we hypothesized that it
      may be responsible for the colouration of the brownish spots. We determined the
      topology and timing of NBAD synthesis and deposition to attain the species
      specific colouration pattern. We demonstrated that during the first hours the
      colour of the brownish spots was principally determined by the tanning of the
      hairs. Haemolymph circulation through the veins is required to tan the wings. We
      confirmed that soon after wing spreading, most of the wing epidermal cells
      disappeared. Thus, the tanning of the brown spots was accomplished when the wing
      lamina was devoid of cells. NBAD synthase (NBAD-S; Ebony protein in D.
      melanogaster) activity in wings was detected in pharate adults and lasted several
      days after the emergence, even after the end of the tanning process. This
      observation is in contrast to epidermal NBAD-S activity in the body, where it was
      nearly undetectable 48 h post emergence. Our results indicate that NBAD-S was
      exported and deposited into the extracellular matrix of the brown spot areas
      before cell death and that tanning occurs through gradual export of NBAD
      precursors (dopamine and b-alanine) from veins.

PMID- 29656101
TI  - Diurnal and developmental differences in gene expression between adult dispersing
      and flightless morphs of the wing polymorphic cricket, Gryllus firmus:
      Implications for life-history evolution.
AB  - The functional basis of life history adaptation is a key topic of research in
      life history evolution. Studies of wing-polymorphism in the cricket Gryllus
      firmus have played a prominent role in this field. However, prior in-depth
      investigations of morph specialization have primarily focused on a single
      hormone, juvenile hormone, and a single aspect of intermediary metabolism, the
      fatty-acid biosynthetic component of lipid metabolism. Moreover, the role of
      diurnal variation in life history adaptation in G. firmus has been understudied,
      as is the case for organisms in general. Here, we identify genes whose expression
      differs consistently between the morphs independent of time-of-day during early
      adulthood, as well as genes that exhibit a strong pattern of morph-specific
      diurnal expression. We find strong, consistent, morph-specific differences in the
      expression of genes involved in endocrine regulation, carbohydrate and lipid
      metabolism, and immunity - in particular, in the expression of an insulin-like
      peptide precursor gene and genes involved in triglyceride production. We also
      find that the flight-capable morph exhibited a substantially greater number of
      genes exhibiting diurnal change in gene expression compared with the flightless
      morph, correlated with the greater circadian change in the hemolymph juvenile
      titer in the dispersing morph. In fact, diurnal differences in expression within
      the dispersing morph at different times of the day were significantly greater in
      magnitude than differences between dispersing and flightless morphs at the same
      time-of-day. These results provide important baseline information regarding the
      potential role of variable gene expression on life history specialization in
      morphs of G. firmus, and the first information on genetically-variable, diurnal
      change in gene expression, associated with a key life history polymorphism. These
      results also suggest the existence of prominent morph-specific circadian
      differences in gene expression in G. firmus, possibly caused by the morph
      specific circadian rhythm in the juvenile hormone titer.

PMID- 29656102
TI  - Activity in vitro and in vivo against Trypanosoma cruzi of a furofuran lignan
      isolated from Piper jericoense.
AB  - Piperaceae species are abundant in the tropics and are important components of
      secondary vegetation. Many of these plants have received considerable attention
      due to their wide range of biological activities. Here, the trypanocidal activity
      of extracts and fractions with different polarities obtained from Colombian Piper
      jericoense plant was evaluated. A furofuran lignan, (1S,3aS,4S,6aS)-1-(3',4'
      dimethoxyphenyl)-4-(3",4"-methylendioxyphenyl)hexahydrofuro[3,4-c]furan, (1), was
      isolated from Colombian Piper jericoense leaves ethyl acetate extract. Its
      relative configuration at the stereogenic centers was established on the basis of
      various spectroscopic analyses, including 1D- (1H, 13C, and DEPT) and 2D-NMR
      (COSY, NOESY, HMQC and HMBC) and a 2D INADEQUATE NMR experiment as well as by
      comparison of their spectral data with those of related compounds such as (+)
      Kobusin (2). The activity against Trypanosoma cruzi indicated that compound 1 was
      active against all parasite forms (epimastigote, amastigote and trypomastigote)
      and presented lower toxicity than the reference drug, benznidazole (Bz),
      evidenced by a selective index of 18.4 compared to that of Bz, which was 6.7.
      Moreover, this compound inhibited the infectious process, and it was active in
      infected mice in the acute phase. This compound significantly inhibited the T.
      cruzi Fe-SOD enzyme, whereas Cu/Zn-SOD from human cells was not affected.
      Ultrastructural analyses, together with metabolism-excretion studies in the
      parasite, were also performed to identify the possible mechanism of action of the
      tested compound. Interestingly, the lignan affected the parasite structure, but
      it did not alter the energetic metabolism.

PMID- 29656103
TI  - Phylogeny of a cosmopolitan family of morphologically conserved trapdoor spiders
      (Mygalomorphae, Ctenizidae) using Anchored Hybrid Enrichment, with a description
      of the family, Halonoproctidae Pocock 1901.
AB  - The mygalomorph family Ctenizidae has a world-wide distribution and currently
      contains nine genera and 135 species. However, the monophyly of this group has
      long been questioned on both morphological and molecular grounds. Here, we use
      Anchored Hybrid Enrichment (AHE) to gather hundreds of loci from across the
      genome for reconstructing the phylogenetic relationships among the nine genera
      and test the monophyly of the family. We also reconstruct the possible ancestral
      ranges of the most inclusive clade recovered. Using AHE, we generate a
      supermatrix of 565 loci and 115,209 bp for 27 individuals. For the first time,
      analyses using all nine genera produce results definitively establishing the non
      monophyly of Ctenizidae. A lineage formed exclusively by representatives of South
      African Stasimopus was placed as the sister group to the remaining taxa in the
      tree, and the Mediterranean Cteniza and Cyrtocarenum were recovered with high
      support as sister to exemplars of Euctenizidae, Migidae, and Idiopidae. All the
      remaining genera-Bothriocyrtum, Conothele, Cyclocosmia, Hebestatis, Latouchia,
      and Ummidia-share a common ancestor. Based on these results, we formally elevate
      this clade to the level of family. Our results definitively establish both the
      non-monophyly of the Ctenizidae and non-validity of the subfamilies Ummidiinae
      and Ctenizinae. In order to establish the placement of the remaining three
      ctenizid genera, Cteniza, Cyrtocarenum, and Stasimopus, thorough analyses within
      the context of a complete mygalomorph phylogenetic framework are needed. We
      formally describe the family Halonoproctidae Pocock 1901 and infer that the
      family's most recent common ancestor was likely distributed in western North
      America and Asia.

PMID- 29656104
TI  - Oligocene origin and drivers of diversification in the genus Sticta (Lobariaceae,
      Ascomycota).
AB  - A major challenge to evolutionary biologists is to understand how biodiversity is
      distributed through space and time and across the tree of life. Diversification
      of organisms is influenced by many factors that act at different times and
      geographic locations but it is still not clear which have a significant impact
      and how drivers interact. To study diversification, we chose the lichen genus
      Sticta, by sampling through most of the global range and producing a time tree.
      We estimate that Sticta originated about 30 million years ago, but biogoegraphic
      analysis was unclear in estimating the origin of the genus. Furthermore, we
      investigated the effect of dispersal ability finding that Sticta has a high
      dispersal rate, as collections from Hawaii showed that divergent lineages
      colonized the islands at least four times. Symbiont interactions were
      investigated using BiSSE to understand if green-algal or cyanobacterial symbiont
      interactions influenced diversification, only to find that the positive results
      were driven almost completely by Type I error. On the other hand, another BiSSE
      analysis found that an association with Andean tectonic activity increases the
      speciation rate of species.

PMID- 29656105
TI  - Mitochondrial introgression obscures phylogenetic relationships among manakins of
      the genus Lepidothrix (Aves: Pipridae).
AB  - Lepidothrix is the most diverse genus of the family Pipridae, with eight
      recognized species. Although the genus' monophyly has been supported by both
      molecular and morphological characters, phylogenetic relationships and species
      limits within Lepidothrix remain uncertain. In the present study, we combined
      molecular sequences of mitochondrial (ND2 and COI) and nuclear (MYO, G3PDh and
      I5BF) markers in a multilocus analysis, to evaluate relationships and inter
      specific limits among L. iris, L. nattereri, and L. vilasboasi, which are known
      to hybridize in eastern Amazonia. The results revealed a complex pattern, whereby
      events of secondary contact and gene flow after isolation and genetic and
      phenotypic differentiation prevented the recuperation of reciprocal monophyly
      among the studied taxa. The mitochondrial data indicate that L. nattereri is
      divided into two non-sister groups, one monophyletic, and the other,
      paraphyletic, with L. iris iris being more closely related to one of the two L.
      nattereri groups, while L. iris eucephala forms an undifferentiated clade with L.
      vilasboasi, probably resulting from an extensive process of mitochondrial
      introgression. In agreement with a previous study based on Single Nucleotide
      Polymorphism (SNP) data, mitochondrial haplotype networks also support that L.
      vilasboasi does not represent a recent "hybrid swarm" between L. iris and L.
      nattereri, but instead a genetically divergent lineage with a separate species
      status. Finally, the sister relationship recovered herein between L. iris iris
      and some western populations of L. nattereri currently in allopatry is also
      apparently explained by mitochondrial introgression, as also supported for
      nuclear genes by SNP data, indicating a complex scenario of past contact and gene
      flow between currently geographically distant Lepidothrix lineages.

PMID- 29656106
TI  - Supporting cognitive control through competition and cooperation in childhood.
AB  - Cognitive control is often engaged in social contexts where actions are socially
      relevant. Yet, little is known about the immediate influence of the social
      context on childhood cognitive control. To examine whether competition or
      cooperation can enhance cognitive control, preschool and school-age children
      completed the AX Continuous Performance Task (AX-CPT) in competitive,
      cooperative, and neutral contexts. Children made fewer errors, responded faster,
      and engaged more cognitive effort, as shown by greater pupil dilation, in the
      competitive and cooperative social contexts relative to the neutral context.
      Competition and cooperation yielded greater cognitive control engagement but did
      not change how control was engaged (reactively or proactively). Manipulating the
      social context can be a powerful tool to support cognitive control in childhood.

PMID- 29656107
TI  - Statistical testing and power analysis for brain-wide association study.
AB  - The identification of connexel-wise associations, which involves examining
      functional connectivities between pairwise voxels across the whole brain, is both
      statistically and computationally challenging. Although such a connexel-wise
      methodology has recently been adopted by brain-wide association studies (BWAS) to
      identify connectivity changes in several mental disorders, such as schizophrenia,
      autism and depression, the multiple correction and power analysis methods
      designed specifically for connexel-wise analysis are still lacking. Therefore, we
      herein report the development of a rigorous statistical framework for connexel
      wise significance testing based on the Gaussian random field theory. It includes
      controlling the family-wise error rate (FWER) of multiple hypothesis testings
      using topological inference methods, and calculating power and sample size for a
      connexel-wise study. Our theoretical framework can control the false-positive
      rate accurately, as validated empirically using two resting-state fMRI datasets.
      Compared with Bonferroni correction and false discovery rate (FDR), it can reduce
      false-positive rate and increase statistical power by appropriately utilizing the
      spatial information of fMRI data. Importantly, our method bypasses the need of
      non-parametric permutation to correct for multiple comparison, thus, it can
      efficiently tackle large datasets with high resolution fMRI images. The utility
      of our method is shown in a case-control study. Our approach can identify altered
      functional connectivities in a major depression disorder dataset, whereas
      existing methods fail. A software package is available at
      https://github.com/weikanggong/BWAS.

PMID- 29656109
TI  - Bile acids are important direct and indirect regulators of the secretion of
      appetite- and metabolism-regulating hormones from the gut and pancreas.
AB  - OBJECTIVE: Bile acids (BAs) facilitate fat absorption and may play a role in
      glucose and metabolism regulation, stimulating the secretion of gut hormones. The
      relative importance and mechanisms involved in BA-stimulated secretion of
      appetite and metabolism regulating hormones from the gut and pancreas is not well
      described and was the purpose of this study. METHODS: The effects of bile acids
      on the secretion of gut and pancreatic hormones was studied in rats and compared
      to the most well described nutritional secretagogue: glucose. The molecular
      mechanisms that underlie the secretion was studied by isolated perfused rat and
      mouse small intestine and pancreas preparations and supported by
      immunohistochemistry, expression analysis, and pharmacological studies. RESULTS:
      Bile acids robustly stimulate secretion of not only the incretin hormones,
      glucose-dependent insulinotropic peptide (GIP), and glucagon-like peptide-1 (GLP
      1), but also glucagon and insulin in vivo, to levels comparable to those
      resulting from glucose stimulation. The mechanisms of GLP-1, neurotensin, and
      peptide YY (PYY) secretion was secondary to intestinal absorption and depended on
      activation of basolateral membrane Takeda G-protein receptor 5 (TGR5) receptors
      on the L-cells in the following order of potency: Lithocholic acid (LCA)
      >Deoxycholicacid (DCA)>Chenodeoxycholicacid (CDCA)> Cholic acid (CA). Thus BAs
      did not stimulate secretion of GLP-1 and PYY from perfused small intestine in
      TGR5 KO mice but stimulated robust responses in wild type littermates. TGR5 is
      not expressed on alpha-cells or beta-cells, and BAs had no direct effects on
      glucagon or insulin secretion from the perfused pancreas. CONCLUSION: BAs should
      be considered not only as fat emulsifiers but also as important regulators of
      appetite- and metabolism-regulating hormones by activation of basolateral
      intestinal TGR5.

PMID- 29656108
TI  - Epoxygenase inactivation exacerbates diet and aging-associated metabolic
      dysfunction resulting from impaired adipogenesis.
AB  - OBJECTIVE: When molecular drivers of healthy adipogenesis are perturbed, this can
      cause hepatic steatosis. The role of arachidonic acid (AA) and its downstream
      enzymatic cascades, such as cyclooxygenase, in adipogenesis is well established.
      The exact contribution of the P450 epoxygenase pathway, however, remains to be
      established. Enzymes belonging to this pathway are mainly encoded by the CYP2J
      locus which shows extensive allelic expansion in mice. Here we aimed to establish
      the role of endogenous epoxygenase during adipogenesis under homeostatic and
      metabolic stress conditions. METHODS: We took advantage of the simpler genetic
      architecture of the Cyp2j locus in the rat and used a Cyp2j4 (orthologue of human
      CYP2J2) knockout rat in two models of metabolic dysfunction: physiological aging
      and cafeteria diet (CAF). The phenotyping of Cyp2j4-/- rats under CAF was
      integrated with proteomics (LC-MS/MS) and lipidomics (LC-MS) analyses in the
      liver and the adipose tissue. RESULTS: We report that Cyp2j4 deletion causes
      adipocyte dysfunction under metabolic challenges. This is characterized by (i)
      down-regulation of white adipose tissue (WAT) PPARgamma and C/EBPalpha, (ii)
      adipocyte hypertrophy, (iii) extracellular matrix remodeling, and (iv)
      alternative usage of AA pathway. Specifically, in Cyp2j4-/- rats treated with a
      cafeteria diet, the dysfunctional adipogenesis is accompanied by exacerbated
      weight gain, hepatic lipid accumulation, and dysregulated gluconeogenesis.
      CONCLUSION: These results suggest that AA epoxygenases are essential regulators
      of healthy adipogenesis. Our results uncover their synergistic role in fine
      tuning AA pathway in obesity-mediated hepatic steatosis.

PMID- 29656110
TI  - Targeting hepatic pyruvate dehydrogenase kinases restores insulin signaling and
      mitigates ChREBP-mediated lipogenesis in diet-induced obese mice.
AB  - OBJECTIVE: Mitochondrial pyruvate dehydrogenase kinases 1-4 (PDKs1-4) negatively
      regulate activity of the pyruvate dehydrogenase complex (PDC) by reversible
      phosphorylation. PDKs play a pivotal role in maintaining energy homeostasis and
      contribute to metabolic flexibility by attenuating PDC activity in various
      mammalian tissues. Cumulative evidence has shown that the up-regulation of PDK4
      expression is tightly associated with obesity and diabetes. In this
      investigation, we test the central hypothesis that PDKs1-4 are a pharmacological
      target for lowering glucose levels and restoring insulin sensitivity in obesity
      and type 2 diabetes (T2D). METHODS: Diet-induced obese (DIO) mice were treated
      with a liver-specific pan-PDK inhibitor 2-[(2,4-dihydroxyphenyl)
      sulfonyl]isoindoline-4,6-diol (PS10) for four weeks, and results compared with
      PDK2/PDK4 double knockout (DKO) mice on the same high fat diet (HFD). RESULTS:
      Both PS10-treated DIO mice and HFD-fed DKO mice showed significantly improved
      glucose, insulin and pyruvate tolerance, compared to DIO controls, with lower
      plasma insulin levels and increased insulin signaling in liver. In response to
      lower glucose levels, phosphorylated AMPK in PS10-treated DIO and HFD-fed DKO
      mice is upregulated, accompanied by decreased nuclear carbohydrate-responsive
      element binding protein (ChREBP). The reduced ChREBP signaling correlates with
      down-regulation of hepatic lipogenic enzymes (ACC1, FAS, and SCD1), leading to
      markedly diminished hepatic steatosis in both study groups, with lower
      circulating cholesterol and triacylglyceride levels as well as reduced fat mass.
      PS10-treated DIO as well as DKO mice showed predominant fatty acid over glucose
      oxidation. However, unlike systemic DKO mice, increased hepatic PDC activity
      alone in PS10-treated DIO mice does not raise the plasma total ketone body level.
      CONCLUSION: Our findings establish that specific targeting of hepatic PDKs with
      the PDK inhibitor PS10 is an effective therapeutic approach to maintaining
      glucose and lipid homeostasis in obesity and T2D, without the harmful
      ketoacidosis associated with systemic inhibition of PDKs.

PMID- 29656111
TI  - Circulating histocompatibility antigen (HLA) gene products may help differentiate
      benign from malignant indeterminate pulmonary lesions.
AB  - BACKGROUND: This study explores the potential diagnostic utility of soluble Human
      Leukocyte Antigen (sHLA) molecules differentially released by lung adenocarcinoma
      and benign lung lesions. METHODS: Conditioned media from the NSCLC cell lines
      H358 and H1703 were immunoblotted for soluble isoforms of major
      histocompatibility complex (MHC) class I (ABC) and II (DRB1, DMB, and DQ)
      antigens. Sera from 25 patients with benign and 25 patients with malignant
      lesions were similarly evaluated to appraise the potential diagnostic value.
      RESULTS: Higher concentrations of soluble HLA class I molecules were observed in
      conditioned medium for the highly-invasive H1703 cell line, relative to the more
      indolent H358 cells. Evaluation of these markers against a cohort of 50 cases
      demonstrated that patients with malignant lesions possess higher levels of HLA
      class I and II molecules relative to those with benign lesions (p < 0.05), with
      exception to the primary isoform, DQA1, which was suppressed in malignancies. An
      analysis of biomarker performance via ROC analysis revealed promising performance
      (AUC > 0.75) for DMB and the 26 kDa isoform of DQ in distinguishing lesion
      pathology. CONCLUSIONS: Soluble HLA molecules may have diagnostic value for early
      stage NSCLC. Validation studies are currently underway using sera from a lung
      cancer screening cohort.

PMID- 29656112
TI  - Influence of immunosuppressive drugs on the CD30 molecule in kidney transplanted
      patients.
AB  - BACKGROUND: Soluble CD30 (sCD30) is a suggested marker for kidney transplantation
      outcomes. We investigated whether sCD30 serum levels are influenced by
      immunosuppression and whether they correlate with findings in protocol biopsies
      and with CD30 gene expression in peripheral blood mononuclear cells (PBMC).
      METHODS: We studied 118 kidney transplant recipients that initially received
      tacrolimus (TAC) and, at month-3, were converted or not to sirolimus (SRL).
      RESULTS: sCD30 serum levels gradually declined after transplantation, being the
      decline more pronounced in the SRL group. CD30 gene expression in PBMC was higher
      in the SRL group than in the TAC group. Patients with IF/TA >= I in the month-24
      protocol biopsy had higher sCD30 levels than patients without IF/TA, in the SRL
      group (P = .03) and in the TAC group (P = .07). CD30+ cells were observed in
      three out of 10 biopsies with inflammatory infiltrate from the SRL group. In
      mixed lymphocyte cultures, SRL and TAC diminished the number of CD30+ T cells and
      the sCD30 levels in the supernatant, but the effect of SRL was stronger.
      CONCLUSIONS: Overall, sCD30 levels are lower in SRL-treated patients, but the
      association between increased sCD30 levels and IF/TA at month-24 post
      transplantation is stronger in SRL than in TAC-treated patients.

PMID- 29656114
TI  - Synergistic action of dual IGF1/R and MEK inhibition sensitizes childhood acute
      lymphoblastic leukemia (ALL) cells to cytotoxic agents and involves
      downregulation of STAT6 and PDAP1.
AB  - Heterogeneous upregulation of multiple prosurvival pathways underlies resistance
      to damage-induced apoptosis in acute lymphoblastic leukemia (ALL) cells despite
      normal p53 responses. Here, we show that the dual combination of insulin-like
      growth factor 1 (IGF1)/IGF1 receptor (IGF1/R) and mitogen-activated protein
      kinase/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibition using
      AG1024 + U0126 can sensitize apoptosis-resistant ALL cells to ionizing radiation
      induced DNA damage irrespective of effect of single pathway inhibition in vitro.
      This AG1024 + U0126 combination also significantly potentiates the ability of the
      core chemotherapy compounds vincristine, dexamethasone, and daunorubicin to kill
      ALL cells in vitro. Evidence of the synergistic action of AG1024 + U0126 in
      samples with variable basal levels of phosphorylated IGF1/Rbeta and ERK1/2
      suggested additional targets of this drug combination. Consistent with this, gene
      expression profiling identified 32 "synergy genes" differentially targeted by
      IGF1/R + MEK inhibition and, among these, Signal transducer and activator of
      transcription 6 (STAT6) and platelet-derived growth factor-associated protein 1
      (PDAP1) were the most differentially downregulated cluster. Pearson correlation
      analysesrevealed that STAT6 and PDAP1 display significant expression codependency
      and a common expression pattern linked with other key "synergy" genes, supporting
      their predicted role in an STAT6-ERK-nuclear factor kappa beta (NF-kappaB)
      network. Knockdown studies revealed that loss of STAT6, but not PDAP1, impinges
      on the cell cycle, causing reduced numbers of viable cells. In combination with
      daunorubicin, STAT6 loss has an additive effect on cell killing, whereas PDAP1
      loss is synergistic, indicating an important role of PDAP1 in the cellular
      response to this anthracycline. Inhibition of STAT6 or PDAP1 may therefore
      represent a potential novel therapeutic strategy for resistant ALL by enhancing
      sensitivity to chemotherapy.

PMID- 29656113
TI  - Conserved association of Argonaute 1 and 2 proteins with miRNA and siRNA pathways
      throughout insect evolution, from cockroaches to flies.

PMID- 29656115
TI  - Autophagy as a pharmacological target in hematopoiesis and hematological
      disorders.
AB  - Autophagy is involved in many cellular processes, including cell homeostasis,
      cell death/survival balance and differentiation. Autophagy is essential for
      hematopoietic stem cell survival, quiescence, activation and differentiation. The
      deregulation of this process is associated with numerous hematological disorders
      and pathologies, including cancers. Thus, the use of autophagy modulators to
      induce or inhibit autophagy emerges as a potential therapeutic approach for
      treating these diseases and could be particularly interesting for differentiation
      therapy of leukemia cells. This review presents therapeutic strategies and
      pharmacological agents in the context of hematological disorders. The pros and
      cons of autophagy modulators in therapy will also be discussed.

PMID- 29656116
TI  - Chromogranin-A and its derived peptides and their pharmacological effects during
      intestinal inflammation.
AB  - The gastrointestinal tract is the largest endocrine organ that produces a broad
      range of active peptides. Mucosal changes during inflammation alter the
      distribution and products of enteroendocrine cells (EECs) that play a role in
      immune activation and regulation of gut homeostasis by mediating communication
      between the nervous, endocrine and immune systems. Patients with inflammatory
      bowel disease (IBD) typically have altered expression of chromogranin (CHG)-A
      (CHGA), a major soluble protein secreted by EECs that functions as a pro-hormone.
      CHGA gives rise to several bioactive peptides that have direct or indirect
      effects on intestinal inflammation. In IBD, CHGA and its derived peptides are
      correlated with the disease activity. In this review we describe the potential
      immunomodulatory roles of CHGA and its derived peptides and their clinical
      relevance during the progression of intestinal inflammation. Targeting CHGA and
      its derived peptides could be of benefit for the diagnosis and clinical
      management of IBD patients.

PMID- 29656117
TI  - Baicalin modulates the Treg/Teff balance to alleviate uveitis by activating the
      aryl hydrocarbon receptor.
AB  - Autoimmune uveitis is a sight-threatening ocular inflammatory disorder.
      Immunological inflammation is regarded as the key to pathogenesis in autoimmune
      uveitis. Baicalin, the major bioactive component of Scutellaria baicalensis,
      possesses immunomodulatory properties. However, the role of baicalin in uveitis
      and its underlying mechanisms remain unclear. In the current study, we found that
      baicalin treatment obviously inhibited the intraocular inflammatory process in
      mice with experimental autoimmune uveitis, along with clear declines in
      infiltrated inflammatory cells and inflammatory cytokine transcription in the
      retina and draining lymph nodes. Furthermore, baicalin treatment increased the
      frequency and number of regulatory T cells and decreased the frequency and number
      of effector T cells (Th1 and Th17 cells) in the draining lymph nodes of mice with
      experimental autoimmune uveitis. In vitro, baicalin treatment suppressed
      interphotoreceptor retinoid binding protein-specific CD4+ T cell proliferation
      and converted CD4+ T cell differentiation. Furthermore, the expression of aryl
      hydrocarbon receptor was activated by baicalin treatment. Baicalin-mediated
      modulation of CD4+ T cell differentiation was partially abrogated by the
      suppression of aryl hydrocarbon receptor. These findings suggest that baicalin
      modulates the Treg/Teff balance and CD4+ T cell proliferation to ameliorate
      experimental autoimmune uveitis by activating the aryl hydrocarbon receptor.

PMID- 29656118
TI  - Job loss, firm-level heterogeneity and mortality: Evidence from administrative
      data.
AB  - This paper estimates the effect of job loss on mortality for older male workers
      with a strong labor force attachment. Using Dutch administrative data, we find
      that job loss due to firm closure increased the probability of death within five
      years by a sizable 0.60 percentage points. Importantly, this effect is estimated
      using a model that controls for firm-level worker characteristics, such as lagged
      firm-level annual average mortality rates. On the mechanism driving the effect of
      job loss on mortality, we provide evidence for an effect running through stress
      and changes in life style.

PMID- 29656119
TI  - State of play and future direction with NOACs: An expert consensus.
AB  - Atrial fibrillation (AF) and venous thromboembolism (VTE) are cardiovascular
      conditions significant in contemporary practice. In both, the use of
      anticoagulation with vitamin K antagonists (VKAs) has been traditionally used to
      prevent adverse events. However, VKA therapy is associated with challenges
      relating to dose maintenance, the need to monitor anticoagulation, and bleeding
      risks. The non-vitamin K oral anticoagulants (NOACs) are becoming accepted as a
      clear alternative to VKA therapy for both AF and VTE management. The aim of this
      paper was to review contemporary evidence on the safety of NOACs in both
      conditions. A comprehensive literature review was conducted to explore key safety
      issues and expert consensus was achieved from eight professionals specialised in
      AF and VTE care. Consensus-based statements were formulated where available
      evidence was weak or contradictory. The expert statements in this paper form a
      key overview of the safety of NOACs compared with VKA therapy, and the
      comparative safety of different NOACs. It is apparent that a detailed patient
      work-up is required in order to identify and manage individual risk factors for
      bleeding and thrombosis prior to NOAC therapy. Additional measures, such as dose
      reductions, may also be used to maintain the safety of NOACs in practice.

PMID- 29656120
TI  - Systemic inflammatory response syndromes in the era of interventional cardiology.
AB  - Systemic inflammatory response syndrome (SIRS), initially reported after
      cardiovascular surgery, has been described after various interventional
      cardiology procedures, including endovascular/thoracic aortic repair
      (EVAR/TEVAR), implantation of heart rhythm devices, percutaneous coronary
      intervention (PCI), electrophysiology procedures (EP), and transcatheter aortic
      valve implantation (TAVI). In these settings, a comprehensive understanding of
      the triggers, pathogenesis as well as a common diagnostic/therapeutic algorithm
      is lacking and will be discussed in this review. SIRS occurs in about 40% and 50%
      of patients undergoing TEVAR/EVAR and TAVI respectively; it affects 0.1% of
      patients undergoing implantation of heart rhythm devices. Prevalence is unknown
      after PCI or EP. Clinical presentation includes fever, dyspnoea/tachypnoea,
      tachycardia, weakness, chest pain and pericardial/pleural effusion. Several
      triggers can be identified, related to implanted devices, biomaterial, and
      procedural aspects (prolonged hypotension, aneurysm thrombus manipulation, active
      fixation atrial leads, coronary microembolization, balloon dilatation/stent
      implantantation, contrast medium, coronary/myocardial microperforation).
      Nonetheless, these triggers share three main pathogenic pathways leading to SIRS
      clinical manifestations: leucocytes activation, endothelial injury/activation,
      and myocardial/pericardial injury. Therapy consists of non-steroidal agents, with
      corticosteroids as second-line treatment in non-responders. Although a benign
      evolution is reported after implantation of heart rhythm devices, PCI and EP,
      major adverse events may occur after EVAR/TEVAR and TAVI at short- and mid-term
      follow up.

PMID- 29656121
TI  - Molecular mechanism of selenoprotein P synthesis.
AB  - BACKGROUND: Selenoprotein synthesis requires the reinterpretation of a UGA stop
      codon as one that encodes selenocysteine (Sec), a process that requires a set of
      dedicated translation factors. Among the mammalian selenoproteins, Selenoprotein
      P (SELENOP) is unique as it contains a selenocysteine-rich domain that requires
      multiple Sec incorporation events. SCOPE OF REVIEW: In this review we elaborate
      on new data and current models that provide insight into how SELENOP is made.
      MAJOR CONCLUSIONS: SELENOP synthesis requires a specific set of factors and
      conditions. GENERAL SIGNIFICANCE: As the key protein required for proper selenium
      distribution, SELENOP stands out as a lynchpin selenoprotein that is essential
      for male fertility, proper neurologic function and selenium metabolism.

PMID- 29656122
TI  - Selenoprotein synthesis and regulation in Archaea.
AB  - BACKGROUND: The major biological form of selenium is that of the co
      translationally inserted amino acid selenocysteine (Sec). In Archaea, the
      majority of proteins containing Sec, selenoproteins, are involved in
      methanogenesis. However, the function of this residue is often not known because
      selenium-independent homologs of the selenoproteins can be employed, sometimes
      even in one organism. SCOPE OF REVIEW: This review summarizes current knowledge
      about the selenoproteins of Archaea, the metabolic pathways where they are
      involved, and discusses the (potential) function of individual Sec residues.
      Also, what is known about the "archaeal" way of selenoprotein synthesis, and the
      regulatory mechanism leading to the replacement of the selenoproteins with
      selenium-independent homologs, will be presented. Where appropriate, similarities
      with (and differences to) the respective steps employed in the other two domains,
      Bacteria and Eukarya, will be emphasized. MAJOR CONCLUSIONS: Genetic and
      biochemical studies guided by analysis of genome sequences of Sec-encoding
      archaea has revealed that the pathway of Sec synthesis in Archaea and Eukarya are
      principally identical and that Sec insertion in Eukarya probably evolved from an
      archaeal mechanism employed prior to the separation of the archaeal and eukaryal
      lines of decent. GENERAL SIGNIFICANCE: In light of the emerging close
      phylogenetic relationship of Eukarya and Archaea, archaeal models may be highly
      valuable tools for unraveling "eukaryotic" principles in molecular and cell
      biology.

PMID- 29656124
TI  - Development of an improved rapid BACpro(r) protocol and a method for direct
      identification from blood-culture-positive bottles using matrix-assisted laser
      desorption ionization time-of-flight mass spectrometry.
AB  - Matrix-assisted laser desorption ionization time-of-flight mass spectrometry
      (MALDI-TOF MS) has been incorporated into pathogenic bacterial identification
      methods and has improved their rapidity. Various methods have been reported to
      directly identify bacteria with MALDI-TOF MS by pretreating culture medium in
      blood culture bottles. Rapid BACpro(r) (Nittobo Medical Co., Ltd.) is a
      pretreatment kit for effective collection of bacteria with cationic copolymers.
      However, the Rapid BACpro(r) pretreatment kit is adapted only for MALDI Biotyper
      (Bruker Daltonics K.K.), and there has been a desire to expand its use to VITEK
      MS (VMS; bioMerieux SA). We improved the protocol and made it possible to analyze
      with VMS. The culture medium bacteria collection method was changed to a method
      with centrifugation after hemolysis using saponin; the cationic copolymer
      concentration was changed to 30% of the original concentration; the sequence with
      which reagents were added was changed; and a change was made to an ethanol/formic
      acid extraction method. The improved protocol enhanced the identification
      performance. When VMS was used, the identification rate was 100% with control
      samples. With clinical samples, the identification agreement rate with the cell
      smear method was 96.3%. The improved protocol is effective in blood culture rapid
      identification, being both simpler and having an improved identification
      performance compared with the original.

PMID- 29656123
TI  - Selenium supplementation prevents metabolic and transcriptomic responses to
      cadmium in mouse lung.
AB  - BACKGROUND: The protective effect of selenium (Se) on cadmium (Cd) toxicity is
      well documented, but underlying mechanisms are unclear. METHODS: Male mice fed
      standard diet were given Cd (CdCl2, 18 MUmol/L) in drinking water with or without
      Se (Na2SeO4, 20 MUmol/L) for 16 weeks. Lungs were analyzed for Cd concentration,
      transcriptomics and metabolomics. Data were analyzed with biostatistics,
      bioinformatics, pathway enrichment analysis, and combined transcriptome
      metabolome-wide association study. RESULTS: Mice treated with Cd had higher lung
      Cd content (1.7 +/- 0.4 pmol/mg protein) than control mice (0.8 +/- 0.3 pmol/mg
      protein) or mice treated with Cd and Se (0.4 +/- 0.1 pmol/mg protein). Gene set
      enrichment analysis of transcriptomics data showed that Se prevented Cd effects
      on inflammatory and myogenesis genes and diminished Cd effects on several other
      pathways. Similarly, Se prevented Cd-disrupted metabolic pathways in amino acid
      metabolism and urea cycle. Integrated transcriptome and metabolome network
      analysis showed that Cd treatment had a network structure with fewer gene
      metabolite clusters compared to control. Centrality measurements showed that Se
      counteracted changes in a group of Cd-responsive genes including Zdhhc11,
      (protein-cysteine S-palmitoyltransferase), Ighg1 (immunoglobulin heavy constant
      gamma-1) and associated changes in metabolite concentrations. CONCLUSION: Co
      administration of Se with Cd prevented Cd increase in lung and prevented Cd
      associated pathway and network responses of the transcriptome and metabolome. Se
      protection against Cd toxicity in lung involves complex systems responses.
      GENERAL SIGNIFICANCE: Environmental Cd stimulates proinflammatory and profibrotic
      signaling. The present results indicate that dietary or supplemental Se could be
      useful to mitigate Cd toxicity.

PMID- 29656125
TI  - Strategic ultrasound-induced stress response of lactic acid bacteria on
      enhancement of beta-glucosidase activity for bioconversion of isoflavones in
      soymilk.
AB  - The purpose of the study is to develop the new methodology of strategic
      ultrasound treatment on lactic acid bacteria (LAB) to induce stress response for
      the enhancement of beta-glucosidase activity that can be used for the
      biotransformation of glucosides into aglycones isoflavones in soymilk. Among the
      five LAB tested, Lactobacillus acidophilus BCRC 10695 showed the best ability to
      release beta-glucosidase for further ultrasonic stimulation to induce proper
      stress response. With ultrasound (20 kHz, amplitude at 20%) to irradiate on L.
      acidophilus BCRC 10695 at stationary phase of growth for 2 min and 24 h of re
      incubation, the beta-glucosidase activity was enhanced to 3.91 U/ml, which was
      1.82 times of that without ultrasound treatment. Using the ultrasound-treated L.
      acidophilus BCRC 10695 to ferment soymilk, the fraction of aglycones in total
      isoflavones in soymilk was effectively increased from 21.8% initially to 97.9% in
      24 h. The strategic ultrasound treatment on L. acidophilus BCRC 10695
      demonstrated promotion of beta-glucosidase activity, and this methodology had the
      potential to be applied in the production of functional soymilk by adding
      probiotics LAB to increase the bioactive isoflavones and nutritional values for
      human health.

PMID- 29656126
TI  - Epigallocatechin-3-gallate protects Kuruma shrimp Marsupeneaus japonicus from
      white spot syndrome virus and Vibrio alginolyticus.
AB  - Epigallocatechin-3-gallate (EGCG) is the most abundant catechin in green tea and
      exhibits potential antibacterial and anticancer activities. In this study, EGCG
      was used in pathogen-challenge experiments in shrimp to discover its effect on
      the innate immune system of an invertebrate. Kuruma shrimp Marsupeneaus japonicus
      was used as an experimental model and challenged with white spot syndrome virus
      (WSSV) and the Gram-negative bacterium Vibrio alginolyticus. Pathogen-challenge
      experiments showed that EGCG pretreatment significantly delayed and reduced
      mortality upon WSSV and V. alginolyticus infection, with VP-28 copies of WSSV
      also reduced. Quantitative reverse transcription polymerase chain reaction
      revealed the positive influence of EGCG on several innate immune-related genes,
      including IMD, proPO, QM, myosin, Rho, Rab7, p53, TNF-alpha, MAPK, and NOS, and
      we observed positive influences on three immune parameters, including total
      hemocyte count and phenoloxidase and superoxide dismutase activities, by EGCG
      treatment. Additionally, results showed that EGCG treatment significantly reduced
      apoptosis upon V. alginolyticus challenge. These results indicated the positive
      role of EGCG in the shrimp innate immune system as an enhancer of immune
      parameters and an inhibitor of apoptosis, thereby delaying and reducing mortality
      upon pathogen challenge. Our findings provide insight into potential therapeutic
      or preventive functions associated with EGCG to enhance shrimp immunity and
      protect shrimp from pathogen infection.

PMID- 29656127
TI  - The protective effects of taurine on oxidative stress, cytoplasmic free-Ca2+ and
      apoptosis of pufferfish (Takifugu obscurus) under low temperature stress.
AB  - The present study was aimed to investigate the low temperature toxicity and its
      protection by taurine in pufferfish. The experimental basal diets supplemented
      with taurine at the rates of 250 (control), 550, 850, 1140, 1430, 1740 mg kg-1
      were fed to fish for 8 weeks. The results showed that fish fed diet with taurine
      had significantly improved weight gain and specific growth rate. After the
      feeding trial, the fish were then exposed to low temperature stress. The results
      showed that low temperature stress could induce reactive oxygen species (ROS)
      generation, disturb the cytoplasm Ca2+ homeostasis, and lead to oxidative stress
      and apoptosis. Compared with the control group, dietary taurine supplementation
      groups increased antioxidant enzyme genes such as manganese superoxide dismutase
      (Mn-SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and catalase
      (CAT), heat shock proteins (HSP70) and complement C3 (C3) mRNA levels under low
      temperature stress. Meanwhile, dietary taurine supplementation groups reduced ROS
      generation, and stabilized the cytoplasm Ca2+ under low temperature stress.
      Furthermore, dietary taurine supplementation groups reduced apoptosis via
      decreasing caspase-3 activity. This is the first report to demonstrate the
      mechanisms of taurine against low temperature stress in fish.

PMID- 29656128
TI  - Agrobacterium rhizogenes-mediated transformation of a dioecious plant model
      Silene latifolia.
AB  - Silene latifolia serves as a model species to study dioecy, the evolution of sex
      chromosomes, dosage compensation and sex-determination systems in plants.
      Currently, no protocol for genetic transformation is available for this species,
      mainly because S. latifolia is considered recalcitrant to in vitro regeneration
      and infection with Agrobacterium tumefaciens. Using cytokinins and their
      synthetic derivatives, we markedly improved the efficiency of regeneration.
      Several agrobacterial strains were tested for their ability to deliver DNA into
      S. latifolia tissues leading to transient and stable expression of the GUS
      reporter. The use of Agrobacterium rhizogenes strains resulted in the highest
      transformation efficiency (up to 4.7% of stable transformants) in hairy root
      cultures. Phenotypic and genotypic analyses of the T1 generation suggested that
      the majority of transformation events contain a small number of independent T-DNA
      insertions and the transgenes are transmitted to the progeny in a Mendelian
      pattern of inheritance. In short, we report an efficient and reproducible
      protocol for leaf disc transformation and subsequent plant regeneration in S.
      latifolia, based on the unique combination of infection with A. rhizogenes and
      plant regeneration from hairy root cultures using synthetic cytokinins. A
      protocol for the transient transformation of S.latifolia protoplasts was also
      developed and applied to demonstrate the possibility of targeted mutagenesis of
      the sex linked gene SlAP3 by TALENs and CRISPR/Cas9.

PMID- 29656129
TI  - No difference in implant survivorship and clinical outcomes between full
      cementless and full-cemented fixation in primary total knee arthroplasty: A
      systematic review and meta-analysis.
AB  - BACKGROUND: The debate over the use of cemented or cementless fixation in total
      knee arthroplasty (TKA) has never stopped since cementless fixation was
      introduced. We undertook a systematic review and meta-analysis to evaluate the
      optimal mode of fixation (full-cementless vs. full-cemented) in TKA. METHODS:
      PubMed, Embase, and the Cochrane Library databases up to July 2017 were searched
      to identify randomised controlled trials (RCTs) and quasi-RCTs comparing full
      cementless TKA and full-cemented TKA. The primary outcome was implant
      survivorship. Secondary outcomes included radiological outcomes (maximum total
      point-motion [MTPM], radiolucent line, rotation degree) and clinical outcomes
      (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC] score,
      Knee Society Score [KSS] score, postoperative range of movement, blood loss and
      complications). RESULTS: Seven studies were included in the systematic review and
      meta-analysis. The mean follow-up was 7.1 years (range from 2 to 16.6 years).
      There was no difference in implant survivorship (RR, 0.98; 95% CI, 0.95-1.01; p =
      0.25; I2 = 0%), MTPM (weighted mean difference [WMD], 0.13 mm; 95% CI, -0.69
      0.95; p = 0.75; I2 = 89.3%) and radiolucent line (RR, 1.36; 95% CI, 0.57-3.23; p
      = 0.48; I2 = 54%) between the cementless and cemented methods. There was a mean
      0.22 degrees  more rotation in the full-cementless fixation group (95% CI, 0.13
      0.32; p < 0.01; I2 = 28.5%). There were no significant differences relating to
      clinical outcomes (WOMAC score, KSS score, postoperative range of movement, blood
      loss and complications) between the two fixation groups. CONCLUSIONS: Although
      more overall component rotation is found in full-cementless fixation, the implant
      survivorship and clinical efficacy are likely similar between full-cementless and
      full-cemented fixation. However, future RCTs with similar cementless prosthetic
      coating and longer-term follow-up are still needed to confirm our findings.

PMID- 29656130
TI  - Robotic resection of benign nonadrenal retroperitoneal tumors: A consecutive case
      series.
AB  - BACKGROUND: The deep location, narrow operative space and proximity to major
      vessels make minimally invasive resection of nonadrenal retroperitoneal tumors
      (NTRs) challenging and rarely reported. This study aimed to evaluate the safety
      and feasibility of robotic resection of benign nonadrenal retroperitoneal tumors.
      METHODS: The demographics and perioperative outcomes of a consecutive series of
      patients who underwent robotic NTR resection between January 1, 2015, and August
      30, 2017, were analyzed. RESULTS: Twenty-five patients (9 men and 16 women; mean
      age, 50.5 years) were included in the study. The mean largest tumor diameter was
      4.9 cm, 11 had a tumor larger than 5 cm and 13 had a tumor adherent to major
      vessels. The mean operative time was 139.0 min, and the median estimated blood
      loss was 50.0 mL (interquartile range, 30-80 mL). No patients required conversion
      to laparotomy or blood transfusion. Postoperative morbidities occurred in 3
      patients (12%), and all recovered after conservative treatment. The mean
      postoperative hospital stay was 4.8 days. On histopathological examination all
      the tumors were benign: lymphangioma (8, 32%), schwannoma (5, 20%), lymphatic
      cyst (4, 16%), paraganglioma (2, 8%), bronchogenic cyst (2, 8%), mucinous
      cystadenoma (1, 4%), neurofibroma (1, 4%), ganglioneuroma (1, 4%), and Castleman
      disease (1, 4%). Neither large tumor size nor adherence to major vessels affected
      the perioperative outcomes. CONCLUSIONS: Robotic resection of NRTs is safe and
      feasible even for tumors which were large or adherent to major vessels.

PMID- 29656131
TI  - Postoperative-treatment following open incisional hernia repair: A survey and a
      review of literature.
AB  - INTRODUCTION: Incisional hernias of the abdominal wall are frequent complication
      after laparotomy (9-20%). Open incisional hernia repair with sublay mesh
      placement (SMP) on the posterior rectus sheath is described as being a sufficient
      method for repairing incisional hernia. In order to ensure wound healing and to
      therefore prevent recurrence, carrying an abdominal binder (AB) or a pressure
      dressing (PD) and physical rest for a certain time is the common postoperative
      recommendation, though the evidence for post-operative treatment is low. Hence,
      we conducted a survey to reveal the different recommendations given by surgical
      departments (SD). METHODS: We conducted a survey among 65 German SDs of the XXX
      Hospital Group. The SDs were interviewed about the number of open incisional
      hernia repair with SMP in the time frame of 2013-2014, the known recurrence rate
      (RR), their recommended prescription of the AB/PD and the time of physical rest.
      RESULTS: The head physicians of 48 surgical departments answered the
      questionnaire. The survey revealed 42 different recommendations of postoperative
      treatment. The majority of the SDs advices 4 weeks (20,5%) of physical rest and
      no prescription of the AB (29,5%). No correlation between the known RR and the
      duration of physical rest was detected. No head physician's prescribes a PD.
      CONCLUSIONS: Due to our findings we assume that a short period of physical rest
      is a considerable postoperative treatment following an open incisional hernia
      repair with SMP. By reducing the individual incapacity for work and immobility
      this would have a social-economic impact. The use of a PD may prevent seroma
      formation. Further investigations with randomized clinical trials are mandatory
      to support our hypothesis.

PMID- 29656132
TI  - Acquiring basic and advanced laparoscopic skills in novices using two-dimensional
      (2D), three-dimensional (3D) and ultra-high definition (4K) vision systems: A
      randomized control study.
AB  - AIMS: To compare the performance of novices in laparoscopic peg transfer and
      intra-corporeal suturing tasks in two-dimensional (2D), three-dimensional (3D)
      and ultra-high definition (4K) vision systems. METHODS: Twenty-four novices were
      randomly assigned to 2D, 3D and 4K groups, eight in each group. All participants
      performed the two tasks on a box trainer until reaching proficiency. Their
      performance was assessed based on completion time, number of errors and number of
      repetitions using the validated FLS proficiency criteria. RESULTS: Eight
      candidates in each group completed the training curriculum. The mean performance
      time (in minutes) for the 2D group was 558.3, which was more than that of the 3D
      and 4K groups of 316.7 and 310.4 min respectively (P < 0.0001). The mean number
      of repetitions was lower for the 3D and 4K groups versus the 2D group: 125.9 and
      127.4 respectively versus 152.1 (P < 0.0001). The mean number of errors was lower
      for the 4K group versus the 3D and 2D groups: 1.2 versus 26.1 and 50.2
      respectively (P < 0.0001). CONCLUSION: The 4K vision system improved accuracy in
      acquiring laparoscopic skills for novices in complex tasks, which was shown in
      significant reduction in number of errors compared to the 3D and the 2D vision
      systems. The 3D and the 4K vision systems significantly improved speed and
      accuracy when compared to the 2D vision system based on shorter performance time,
      fewer errors and lesser number of repetitions.

PMID- 29656133
TI  - Reply letter to: Letter to the editor on the article "Assessing associations of
      anaemia with morbidity and mortality following liver transplantation".

PMID- 29656134
TI  - Seroprevalence and risk factors of hepatitis E virus infection in cancer patients
      in eastern China.
AB  - OBJECTIVES: Hepatitis E virus (HEV) is a single-stranded RNA virus infecting a
      variety of animals and humans. Little is known of HEV infection among cancer
      patients in China. This study provides new epidemiological data for the
      prevalence of HEV co-infection in cancer patients, indicating that HEV infection
      is common in this group. METHODS: A total of 950 cancer patients and 950 control
      volunteers from Shandong Province, eastern China, were recruited to participate
      in this investigation. Blood samples from patients and controls were examined for
      anti-HEV IgG and IgM antibodies using ELISAs. RESULTS: The overall seroprevalence
      of IgG and IgM antibodies to HEV was significantly higher in cancer patients
      (247/950, 26.0%) than in controls (123/950, 13.0%) (p<0.001). In cancer patients,
      22.7% of serum samples were anti-HEV IgG-positive, and in control subjects, 11.0%
      were anti-HEV IgG-positive (p<0.001). For IgM antibodies, seroprevalence was 4.2%
      in cancer patients (n=40) and 2.1% in controls (n=20) (p=0.009). The
      seroprevalence of HEV was higher in cancer patients who had dogs in their home
      (31.7%) when compared to other cancer patients. The highest seroprevalence of HEV
      infection was found in leukemia patients (32.3%), followed by liver cancer
      patients (31.1%); the lowest HEV seroprevalence was detected in patients with
      gastric cancer (18.9%). CONCLUSIONS: This investigation revealed that the
      seroprevalence of HEV was significantly higher in cancer patients than in
      controls in eastern China. Therefore, cancer patients are a high-risk population
      and should be kept away from sources of HEV infection.

PMID- 29656135
TI  - Two cases of disseminated infection following live organism anti-cancer vaccine
      administration in cancer patients.
AB  - Vaccines containing live attenuated bacterial or viral organisms are currently
      being investigated as potential therapy for locally advanced or metastatic
      cancers. However, the use of such live organisms in an immunocompromised
      population, such as patients who recently or are currently receiving
      chemotherapy, raises the concern that these organisms can themselves disseminate
      and cause frank infection. We report a hereunto unreported phenomenon of anti
      cancer vaccines (containing live attenuated organisms) leading to frank,
      disseminated infection. We submit that occurrence of this phenomenon must be
      watched for by all members of the interdisciplinary cancer treatment team.

PMID- 29656136
TI  - Streptococcus gallolyticus subsp. pasteurianus meningitis complicated by venous
      sinus thrombosis: A case report.
AB  - A case of Streptococcus gallolyticus subsp. pasteurianus meningitis, unusually
      occurring in a splenectomized patient and complicated by cerebral venous
      thrombosis, is described. Following presentation with meningism and diagnosis and
      management of S. gallolyticus meningitis, the patient presented again with a
      further 4days of fevers and subsequently developed left-sided paresthesias.
      Cerebral imaging revealed a venous thrombus in the right frontal cortical veins
      and left sigmoid sinus. The patient recovered following 4 weeks of intravenous
      ceftriaxone and anticoagulation with enoxaparin and then warfarin. Apart from the
      splenectomy, no underlying cause was found. The patient was commenced on life
      long prophylactic amoxicillin, given appropriate vaccinations, and anticoagulated
      with warfarin. After initial difficulties, identification of the causative
      organism to the subspecies level was confirmed by analysis of short-read whole
      genome sequencing data. This case demonstrates two features that have not
      previously been reported for S. gallolyticus subsp. pasteurianus infections:
      splenectomy as a potential risk factor and that infection may be complicated by
      cerebral venous thrombosis. The resolution provided by whole genome sequencing
      was valuable in accurately identifying the bacterial subspecies.

PMID- 29656138
TI  - Inosine Monophosphate Dehydrogenase Pharmacogenetics in Hematopoietic Cell
      Transplantation Patients.
AB  - We evaluated inosine monophosphate dehydrogenase (IMPDH) 1 and IMPDH2
      pharmacogenetics in 247 recipient-donor pairs after nonmyeloablative
      hematopoietic cell transplant (HCT). Patients were conditioned with total body
      irradiation + fludarabine and received grafts from related or unrelated donors
      (10% HLA mismatch), with postgraft immunosuppression of mycophenolate mofetil
      (MMF) with a calcineurin inhibitor. Recipient and donor IMPDH genotypes
      (rs11706052, rs2278294, rs2278293) were not associated with day 28 T cell
      chimerism, acute graft-versus-host disease (GVHD), disease relapse,
      cytomegalovirus reactivation, nonrelapse mortality, or overall survival.
      Recipient IMPDH1 rs2278293 genotype was associated with a lower incidence of
      chronic GVHD (hazard ratio, .72; P = .008) in nonmyeloablative HCT recipients.
      Additional studies are needed to confirm these results with the goal of
      identifying predictive biomarkers to MMF that lower GVHD.

PMID- 29656137
TI  - Haploidentical Peripheral Blood Stem Cell Transplantation Demonstrates Stable
      Engraftment in Adults with Sickle Cell Disease.
AB  - We report on the screening and development of haploidentical hematopoietic stem
      cell transplantation (HSCT) for adult patients with clinically aggressive sickle
      cell disease (SCD) at our institution. Of 50 adult SCD patients referred for HSCT
      between January 2014 and March 2017, 20% were denied by insurance. Of 41 patients
      initially screened, 10% lacked an available haploidentical donor, 29% had
      elevated donor-specific antibodies (DSAs), and 34% declined to proceed to HSCT.
      All 10 patients who were transplanted received peripheral blood stem cells. The
      initial 2 were conditioned with alemtuzumab/total body irradiation (TBI) 3 Gy
      followed by post-transplant cyclophosphamide and failed to engraft. The next 8
      patients received the regimen developed at Johns Hopkins University with TBI 3
      Gy. Granulocyte colony-stimulating factor was administered from day +12 in those
      with HbS < 30%. All 8 patients engrafted with a median time to neutrophil >.5 *
      109/L of 22 days (range, 18 to 23). One patient subsequently lost the graft, and
      7 (87.5%) maintained >95% donor cell chimerism at 1-year post-HSCT. Two patients
      developed acute graft-versus-host disease (GVHD) of at least grade II. One had
      chronic GVHD and died >1 year after HSCT of unknown causes. With a median follow
      up of 16 months (range, 11 to 29), 7 patients (87.5%) are alive. Our findings
      suggest that limited insurance coverage, high rate of DSAs, and patient declining
      HSCT may limit the availability of haploidentical HSCT in adult SCD patients. The
      modified Hopkins regimen used here demonstrates high engraftment and low
      morbidity rates and should be tested in larger, multicenter, prospective clinical
      trials.

PMID- 29656139
TI  - Analysis of Clinical Factors and Outcomes Associated with Nonuse of Collected
      Peripheral Blood Stem Cells for Autologous Stem Cell Transplants in Transplant
      Eligible Patients with Multiple Myeloma.
AB  - Collection and storage of peripheral blood stem cells (PBSCs) for use in
      autologous stem cell transplantation (ASCT) upon first disease relapse is an
      accepted practice for eligible patients with multiple myeloma (MM). However,
      little is known about the factors and outcomes associated with nonuse of these
      collected and stored PBSCs by MM patients who intended to have a delayed ASCT.
      From January 1, 2004 to December 31, 2014 we identified 342 patients who
      underwent collection and storage of their PBSCs in anticipation of a delayed ASCT
      upon first disease relapse. Among these, 176 patients (11%) had not proceeded to
      a delayed ASCT at the time of this study analysis. The most common reason for not
      undergoing an ASCT was not experiencing a relapse on first-line therapy (53%, n =
      94). However, 11% of patients (n = 37) who planned for a delayed ASCT were unable
      to undergo an ASCT at disease relapse. Comparison with a control group of MM
      patients who underwent an upfront ASCT suggested a worse overall survival from
      diagnosis in these patients who were ASCT ineligible at disease relapse (112
      versus 80 months, P = .011). This study provides valuable data for patients and
      care providers to take into consideration when deciding on whether to pursue an
      upfront or a delayed ASCT.

PMID- 29656140
TI  - Outcomes after open and laparoscopic appendectomy during pregnancy: A meta
      analysis.
AB  - OBJECTIVES: Acute appendicitis is the most prevalent cause of non-obstetrical
      surgical disease during pregnancy. There is no consensus on the optimal surgical
      management of acute appendicitis in pregnancy. Our aim is to identify surgical
      and obstetrical outcomes of laparoscopic (LA) and open approach (OA) in pregnant
      patients with acute appendicitis. STUDY DESIGN: Medline, Scopus, Google Scholar,
      Cochrane CENTRAL Register of Controlled Trials and Clinicaltrials.gov databases
      were searched for articles published up to May 2017, along with the references of
      all articles. Prospective and retrospective trials reporting outcomes among
      pregnant women undergoing laparoscopic and open appendectomy were included. Of
      the 493 records screened, 20 were eligible for meta-analysis. The Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were
      followed. Statistical meta-analysis was performed using the RevMan 5.3 software.
      RESULTS: A total of 6210 pregnant women from twenty studies were included in meta
      analysis. Laparoscopic appendectomy was associated with significantly lower
      overall complication rates and shorter hospital stays (1835 patients OR 0.48 95%
      CI 0.29, 0.80 p = 0.005). While the open appendectomy group showed prolongation
      of gestational age for term deliveries, laparoscopic appendectomy patients had
      higher rates of fetal loss (543 patients MD -0.46 weeks 95% CI-0.87 to -0.04, p =
      0.03 and 4867 patients OR 1.82 95% CI 1.30 to 2.57, p = 0.0006, respectively).
      CONCLUSIONS: Current literature remains inconclusive on the optimal approach of
      appendectomy in pregnant women. Further larger-volume studies are needed in order
      to elucidate the critical effect of laparoscopic appendectomy on fetal loss
      rates.

PMID- 29656141
TI  - Wnt5a suppresses inflammation-driven intervertebral disc degeneration via a TNF
      alpha/NF-kappaB-Wnt5a negative-feedback loop.
AB  - OBJECTIVE: This study was to investigate the molecular role of Wnt5a on
      inflammation-driven intervertebral disc degeneration (IVDD). METHODS: The
      expression of Wnt5a was analyzed in human nucleus pulposus (NP) tissues with
      immunohistochemical staining. The effects of Wnt5a on matrix production were
      assessed by RT-qPCR and western blotting. Small interfering RNAs (siRNAs),
      promoter deletion assay, and promoter binding site mutant were used to reveal the
      molecular role of Wnt5a in TNF-alpha-induced matrix metalloproteinase (MMP)
      expression. The regulatory effects of TNF-alpha on Wnt5a were investigated with
      pharmachemical inhibitors and siRNA experiment. RESULTS: The expression of Wnt5a
      was elevated in moderately degenerated human NP tissue with similar expression
      pattern of TNF-alpha. In NP cells, Wnt5a significantly increased aggrecan and
      collagen II expression. Inhibition of JNK or interfering Sox9 gene expression
      significantly suppressed Wnt5a-induced matrix production. AP-1(JunB) binding
      sites were located in Sox9 promoter and mutation of these sites sabotaged Wnt5a
      induced Sox9 up-regulation and subsequent matrix genes expression. Notably,
      Wnt5a, which was induced by TNF-alpha, on the other way round suppressed TNF
      alpha-NF-kappaB (p65) signaling and subsequent MMPs expression. In vivo studies
      with MR imaging confirmed the protective role of Wnt5a in IVDD. CONCLUSIONS:
      Wnt5a, which can be induced by TNF-alpha, increased matrix production in a Sox9
      dependent manner through the activation of JNK-AP1 (JunB) signaling, and
      antagonized TNF-alpha-induced up-regulation of MMPs through the inhibition of NF
      kappaB signaling. It indicates that Wnt5a suppresses IVDD through a TNF-alpha/NF
      kappaB-Wnt5a negative-feedback loop.

PMID- 29656142
TI  - Management of foot/ankle osteoarthritis by Australian general practitioners: an
      analysis of national patient-encounter records.
AB  - OBJECTIVE: To document the management of foot/ankle osteoarthritis/arthritis (OA)
      by general practitioners (GP) in Australia. DESIGN: We analysed data from the
      Bettering the Evaluation and Care of Health Program April 2010-March 2016
      inclusive. Patient and GP encounter characteristics were extracted. Data were
      classified by the International Classification of Primary Care, Version 2, and
      summarised using descriptive statistics and 95% confidence intervals (95% CIs)
      around point estimates. RESULTS: The dataset included 583,900 patient-encounter
      records among which foot/ankle OA was managed 621 times, at a rate of 1.1 per
      1000 encounters, with an annual estimated 152,000 GP encounters nationally. The
      management rate was most frequent among patients aged 65-74 years (2.25 per 1000
      encounters). Comorbidities were managed at a rate of 105.8 per 100 encounters,
      the most common being hypertension, and few being other musculoskeletal problems.
      Foot/ankle OA was mostly managed using medication (64.6 per 100 problems), with
      prescription rates far exceeding non-pharmacological strategies such as
      counselling, advice or education (17.7 per 100), or allied health referral (10.1
      per 100). When considering specific health/medical professionals, patients were
      referred to orthopaedic surgeons 8.4 times per 100 foot/ankle problems,
      podiatrists 6.3 times per 100 foot/ankle problems, and physiotherapists 2.6 times
      per 100 foot/ankle problems. CONCLUSIONS: Pharmacological management rates of
      foot/ankle OA were high and substantially exceeded non-pharmacological management
      such as lifestyle advice and allied health referral. Longitudinal studies are
      needed to determine the effectiveness of this care compared to self-management
      and conservative non-drug treatment in people with foot/ankle OA.

PMID- 29656143
TI  - Quantitative imaging of bone-cartilage interactions in ACL-injured patients with
      PET-MRI.
AB  - OBJECTIVE: To investigate changes in bone metabolism by positron emission
      tomography (PET), as well as spatial relationships between bone metabolism and
      magnetic resonance imaging (MRI) quantitative markers of early cartilage
      degradation, in anterior cruciate ligament (ACL)-reconstructed knees. DESIGN:
      Both knees of 15 participants with unilateral reconstructed ACL tears and
      unaffected contralateral knees were scanned using a simultaneous 3.0T PET-MRI
      system following injection of 18F-sodium fluoride (18F-NaF). The maximum pixel
      standardized uptake value (SUVmax) in the subchondral bone and the average T2
      relaxation time in cartilage were measured in each knee in eight knee
      compartments. We tested differences in SUVmax and cartilage T2 relaxation times
      between the ACL-injured knee and the contralateral control knee as well as
      spatial relationships between these bone and cartilage changes. RESULTS:
      Significantly increased subchondral bone 18F-NaF SUVmax and cartilage T2 times
      were observed in the ACL-reconstructed knees (median [inter-quartile-range
      (IQR)]: 5.0 [5.8], 36.8 [3.6] ms) compared to the contralateral knees (median
      [IQR]: 1.9 [1.4], 34.4 [3.8] ms). A spatial relationship between the two markers
      was also seen. Using the contralateral knee as a control, we observed a
      significant correlation of r = 0.59 between the difference in subchondral bone
      SUVmax (between injured and contralateral knees) and the adjacent cartilage T2
      (between the two knees) [P < 0.001], with a slope of 0.49 ms/a.u. This
      correlation and slope were higher in deep layers (r = 0.73, slope = 0.60 ms/a.u.)
      of cartilage compared to superficial layers (r = 0.40, slope = 0.43 ms/a.u.).
      CONCLUSIONS: 18F-NaF PET-MR imaging enables detection of increased subchondral
      bone metabolism in ACL-reconstructed knees and may serve as an important marker
      of early osteoarthritis (OA) progression. Spatial relationships observed between
      early OA changes across bone and cartilage support the need to study whole-joint
      disease mechanisms in OA.

PMID- 29656144
TI  - Short- and long-term management of cases of venom-induced anaphylaxis is
      suboptimal.
AB  - BACKGROUND: Venom-induced anaphylaxis (VIA) accounts for severe reactions.
      However, little is known about the short- and long-term management of VIA
      patients. OBJECTIVE: To assess the short- and long-term management of VIA.
      METHODS: Using a national anaphylaxis registry (C-CARE), we identified VIA cases
      presenting to emergency departments in Montreal and to emergency medical services
      (EMSs) in western Quebec over a 4-year period. Data were collected on clinical
      characteristics, triggers, and management. Consenting patients were contacted
      annually regarding long-term management. Univariate and multivariate logistic
      regressions were used to identify factors associated with epinephrine use,
      allergist assessment, and administration of immunotherapy. RESULTS: Between June
      2013 and May 2017, 115 VIA cases were identified. Epinephrine was administered to
      63.5% (95% confidence interval [CI], 53.9%-72.1%) of all VIA cases by a health
      care professional. Treatment of reactions without epinephrine was more likely in
      reactions occurring at home and in nonsevere cases (no hypotension, hypoxia, or
      loss of consciousness). Among 48 patients who responded to a follow-up
      questionnaire, 95.8% (95% CI, 84.6%-99.3%) were prescribed epinephrine auto
      injector, 68.8% (95% CI, 53.6%-80.9%) saw an allergist who confirmed the allergy
      in 63.6% of cases, and 81.0% of those with positive testing were administered
      immunotherapy. Among cases with follow-up, seeing an allergist was less likely in
      patients with known ischemic heart disease. CONCLUSION: Almost 30% of patients
      with suspected VIA did not see an allergist, only two thirds of those seeing an
      allergist had allergy confirmation, and almost one fifth of those with confirmed
      allergy did not receive immunotherapy. Educational programs are needed to bridge
      this knowledge-to-action gap.

PMID- 29656145
TI  - SQ house dust mite sublingual immunotherapy tablet subgroup efficacy and local
      application site reaction duration.
AB  - BACKGROUND: Allergic rhinitis with or without conjunctivitis (AR/C) is common,
      necessitating evaluation of SQ house dust mite (HDM) sublingual immunotherapy
      (SLIT)-tablet efficacy in various subgroups. OBJECTIVE: To evaluate 12 SQ-HDM
      efficacy and safety across subgroups, and the onset, duration, and recurrence of
      local application site reactions. METHODS: Subgroup (age, sex, race, asthma
      status, and allergen sensitization) efficacy was assessed using pooled data from
      2 previously described trials of daily 12 SQ-HDM vs placebo for AR/C (n = 2,138).
      Efficacy was measured by average total combined rhinitis score (TCRS; rhinitis
      daily symptom plus medication score) during the last 8 weeks of treatment. Safety
      in subgroups and local application site reaction onset, duration, and recurrence
      were evaluated using pooled data from 5 previously described trials of SQ HDM
      SLIT-tablet (n = 2,923). RESULTS: Significant (based on 95% confidence intervals
      [CIs]) reduction in TCRS was seen with 12 SQ-HDM relative to placebo across all
      subgroups, with TCRS improvements ranging from 15% to 25%. The AE profile was
      generally similar within subgroups. Approximately 95% of local application site
      reactions were mild to moderate in severity. Median duration on day 1 of
      treatment for the most common local application site reactions (throat
      irritation, oral pruritus, ear pruritus, and lip swelling) ranged from 30 to 60
      minutes; median first day of onset ranged from days 1 to 4 of treatment; median
      days that reactions recurred ranged from 3 to 12 days. CONCLUSION: Treatment with
      12 SQ-HDM consistently improved symptoms and was well tolerated in relevant
      subgroups of subjects with HDM AR/C. Local application site reactions to 12 SQ
      HDM were typically mild to moderate and transient.

PMID- 29656147
TI  - Liver fibrosis: Direct antifibrotic agents and targeted therapies.
AB  - Liver fibrosis and in particular cirrhosis are the major causes of morbidity and
      mortality of patients with chronic liver disease. Their prevention or reversal
      have become major endpoints in clinical trials with novel liver specific drugs.
      Remarkable progress has been made with therapies that efficiently address the
      cause of the underlying liver disease, as in chronic hepatitis B and C. Highly
      effective antiviral therapy can prevent progression or even induce reversal in
      the majority of patients, but such treatment remains elusive for the majority of
      liver patients with advanced alcoholic or nonalcoholic steatohepatitis, genetic
      or autoimmune liver diseases. Moreover, drugs that would speed up fibrosis
      reversal are needed for patients with cirrhosis, since even with effective causal
      therapy reversal is slow or the disease may further progress. Therefore, highly
      efficient and specific antifibrotic agents are needed that can address advanced
      fibrosis, i.e., the detrimental downstream result of all chronic liver diseases.
      This review discusses targeted antifibrotic therapies that address molecules and
      mechanisms that are central to fibrogenesis or fibrolysis, including strategies
      that allow targeting of activated hepatic stellate cells and myofibroblasts and
      other fibrogenic effector cells. Focus is on collagen synthesis, integrins and
      cells and mechanisms specific including specific downregulation of TGFbeta
      signaling, major extracellular matrix (ECM) components, ECM-crosslinking, and ECM
      receptors such as integrins and discoidin domain receptors, ECM-crosslinking and
      methods for targeted delivery of small interfering RNA, antisense
      oligonucleotides and small molecules to increase potency and reduce side effects.
      With an increased understanding of the biology of the ECM and liver fibrosis and
      an improved preclinical validation, the translation of these approaches to the
      clinic is currently ongoing. Application to patients with liver fibrosis and a
      personalized treatment is tightly linked to the development of noninvasive
      biomarkers of fibrosis, fibrogenesis and fibrolysis.

PMID- 29656146
TI  - Genetics of the extracellular matrix in aortic aneurysmal diseases.
AB  - Aortic aneurysms are morbid conditions that can lead to rupture or dissection and
      are categorized as thoracic (TAA) or abdominal aortic aneurysms (AAA) depending
      on their location. While AAA shares overlapping risk factors with atherosclerotic
      cardiovascular disease, TAA exhibits strong heritability. Human genetic studies
      in the past two decades have successfully identified numerous genes involved in
      both familial and sporadic forms of aortic aneurysm. In this review we will
      discuss the genetic basis of aortic aneurysm, focusing on the extracellular
      matrix and how insights from these studies have informed our understanding of
      human biology and disease pathogenesis.

PMID- 29656148
TI  - Basement membrane mechanics shape development: Lessons from the fly.
AB  - Basement membrane plays a foundational role in the structure and maintenance of
      many tissues throughout the animal kingdom. In addition to signaling to cells
      through cell-surface receptors, basement membrane directly influences the
      development and maintenance of organ shape via its mechanical properties. The
      mechanical properties of basement membrane are dictated by its composition,
      geometry, and crosslinking. Distinguishing between the ways the basement membrane
      influences morphology in vivo poses a major challenge. Drosophila melanogaster,
      already established as a powerful model for the analysis of cell signaling, has
      in recent years emerged as a tractable model for understanding the roles of
      basement membrane stiffness in vivo, in shaping and maintaining the morphology of
      tissues and organs. In addition to the plethora of genetic tools available in
      flies, the major proteins found in vertebrate basement membranes are all present
      in Drosophila. Furthermore, Drosophila has fewer copies of the genes encoding
      these proteins, making flies more amenable to genetic manipulation than
      vertebrate models. Because the development of Drosophila organs has been well
      characterized, these different organ systems offer a variety of contexts for
      analyzing the role of basement membrane in development. The developing egg
      chamber and central nervous system, for example, have been important models for
      assessing the role of basement membrane stiffness in influencing organ shape.
      Studies in the nervous system have also shown how basement membrane stiffness can
      influence cellular migration in vivo. Finally, work in the imaginal wing disc has
      illuminated a distinct mechanism by which basement membrane can alter organ shape
      and size, by sequestering signaling ligands. This mini-review highlights the
      recent discoveries pertaining to basement membrane mechanics during Drosophila
      development.

PMID- 29656149
TI  - Total Laparoscopic Ureteroneocystostomy for Ureteral Endometriosis: A Single
      Center Experience of 160 Consecutive Patients.
AB  - STUDY OBJECTIVE: To investigate the efficacy of laparoscopic ureteroneocystostomy
      in patients with deep infiltrating endometriosis (DIE) with ureteral,
      parametrial, and bowel involvement. DESIGN: Prospective study (Canadian Task
      Force classification II-2). SETTING: Tertiary referral center for endometriosis
      care. PATIENTS: One hundred sixty patients with DIE underwent laparoscopic
      radical eradication and ureteroneocystostomy between January 2009 and December
      2016. INTERVENTIONS: Laparoscopic nerve-sparing radical treatment with
      ureteroneocystostomy, parametrectomy, and, if necessary, segmental bowel
      resection. MEASUREMENTS AND MAIN RESULTS: Surgical eradication was radical, and
      ureteral endometriosis was histologically confirmed in all patients (45.6%
      intrinsic and 54.4% extrinsic). In 58.7% of patients ureteroneocystostomy was
      performed with the psoas hitch technique. Bowel resection was performed in 121
      patients (75.6%), and 115 of them had a concomitant ileostomy (71.9%). Unilateral
      parametrectomy was performed on the left side in 61.9% of patients and on the
      right side in 30% of patients, respectively, whereas bilateral parametrectomy was
      completed in 33 patients (20.6%). Postoperative complications were infrequent: 7
      patients underwent reoperation (4.4%), 8 patients experienced fever (5%), 4
      patients required blood transfusion (2.5%), 3 patients had intestinal fistulas
      (1.9%), and 24 patients experienced impaired bladder voiding (15%) after 6
      months. Mean follow-up time was 20.5 months (range, 1-60). The study reported
      good clinical and surgical results, with a regression of symptoms (p < .001) and
      recurrence of parametrial endometriosis of 1.2% that required opposite-side
      ureteroneocystostomy. CONCLUSION: This is the largest documented series of
      patients with DIE undergoing laparoscopic radical eradication and
      ureteroneocystostomy. The collected data show that in patients with ureteral
      endometriosis, this technique is feasible, effective, and safe and provides good
      results in terms of relapses and symptoms' control.

PMID- 29656150
TI  - Safety, Efficacy, and Cost-Analysis of Percutaneous Endoscopic Gastrostomy and
      Ventriculoperitoneal Shunt Placement in a Simultaneous Surgery.
AB  - BACKGROUND: Limited historical data suggest that concomitant placement of both a
      ventriculoperitoneal (VP) shunt and percutaneous endoscopic gastrostomy (PEG)
      tube is associated with an increased risk of complications, including VP shunt
      infections. Here we compare the outcomes and cost difference between 2 groups of
      patients, one in which a VP shunt and PEG tube were placed in the same operation
      and the other in which separate operations were performed. METHODS: A total of 10
      patients underwent simultaneous placement of a VP shunt and PEG tube. This group
      was compared with a group of 18 patients that underwent separate placements.
      Hospital billing charges were used to compare the total cost of the procedures in
      the 2 groups. RESULTS: Eight of the 10 patients presented with aneurysmal
      subarachnoid hemorrhage. The average length of stay was 25 +/- 2 days for the
      simultaneous procedure group and 43 +/- 7 days for the separate procedures group.
      The average duration of follow-up was 12 +/- 3 months after simultaneous
      placement. No patient in the simultaneous surgery group had signs of infection or
      shunt malfunction at last follow-up. The overall complication rate was
      significantly lower in the simultaneous surgery group. A cost analysis
      demonstrated significant cost savings by completing both procedures in the same
      surgical procedure. CONCLUSIONS: Simultaneous placement of a PEG tube and VP
      shunt is safe, efficacious, and cost-effective. Thus, in patients requiring both
      a VP shunt and PEG tube, placement of both devices in a single surgical procedure
      should be considered.

PMID- 29656151
TI  - Total Hospital Costs and Length of Stay of Endovascular Coiling Versus
      Neurosurgical Clipping for Unruptured Intracranial Aneurysms: Systematic Review
      and Meta-Analysis.
AB  - OBJECTIVE: Comparison of feasibility and safety between endovascular coiling
      versus neurosurgical clipping for the management of unruptured intracranial
      aneurysms (UIAs) has been incrementally reported. However, economic comparison
      has been rarely reported. This meta-analysis aims at qualitatively and
      quantitatively analyzing the difference of hospital costs and length of stay
      between endovascular versus neurosurgical treatment in UIA. METHODS: MEDLINE, the
      Cochrane database, EMBASE, and Web of Science database were searched for cohort
      studies describing economic hospital cost or length of stay in patients with UIA.
      Two authors independently assessed study eligibility and rated quality using the
      Newcastle Ottawa Scale. Ravmen 5.2 was used to perform forest plot analysis.
      RESULTS: Nine studies describing 24,856 UIAs treated with neurosurgical clipping
      and 31,309 UIAs treated with endovascular coiling were included. Meta-analysis
      revealed that the total hospital costs (THCs) were similar between coiling and
      clipping in UIA patients (standard mean difference [SMD]: -0.33, 95% confidence
      interval: -0.68 to 0.02, I2 = 99%, P = 0.07). Subgroup analysis showed that THCs
      of coiling were significantly lower than clipping in the United States but
      opposite in South Korea. One-year medical costs of coiling were similar in both
      groups (SMD: -0.04, 95% CI: -0.08 to 0.00, I2 = 0%, P = 0.07). In addition, the
      length of stay of coiling were significantly shorter than that of clipping (SMD:
      0.69, 95% CI: 0.56-0.81, I2 = 95%, P < 0.001). CONCLUSION: Generally, no
      significant difference in THCs and 1-year medical costs between coiling versus
      clipping in UIAs was observed. However, the length of stay of endovascular
      coiling was much shorter than neurosurgical clipping and decreased over time.

PMID- 29656152
TI  - Occipital Condyle Fractures and Concomitant Cervical Spine Fractures:
      Implications for Management.
AB  - BACKGROUND: Occipital condyle fractures (OCFs) have traditionally been described
      based on anatomic characteristics; however, recent literature has proposed
      management based on biomechanical stability and neural element compression. The
      treatment of biomechanically stable fractures varies between observation and
      cervical immobilization. Before determining the best management approach, an
      understanding of concomitant cervical spine fractures in the presence of OCFs is
      important. The primary aim of this pilot study was to determine the rate of
      occurrence of biomechanically significant cervical spine fractures with OCFs.
      METHODS: A retrospective chart review was performed of 13,363 patients presenting
      to a level 1 trauma center between 2013 and 2017 with a diagnosis of OCF.
      RESULTS: Forty-six patients presented with OCFs, with an average Glasgow Coma
      Scale score of 12 on presentation and an average Injury Severity Score of 23. The
      average patient age was 42.1 years, and 4 patients had bilateral OCFs.
      Approximately 30% of these patients had associated intracranial injuries and 59%
      had an associated cervical spine injury. The overall rate of associated
      potentially biomechanically significant cervical spine fracture was 43.5%.
      Treatment of OCFs included collar immobilization (83%) and observation (17%). The
      average duration of follow-up was 3.37 months. CONCLUSIONS: This study
      characterizes cervical spine fractures that occur concomitantly with OCFs. The
      results indicate that more than one-half of patients with OCFs do not have
      biomechanically significant fractures elsewhere in the cervical spine. This
      subset of patients will be the cohort for a prospective study to assess whether
      collar immobilization is necessary.

PMID- 29656153
TI  - Prevalence of Incidental Clinoid Segment Saccular Aneurysms.
AB  - INTRODUCTION: Clinoid segment aneurysms are cerebral vascular lesions recently
      described in the neurosurgical literature. They arise from the clinoid segment of
      the internal carotid artery, which is the segment limited rostrally by the dural
      carotid ring and caudally, by the carotid-oculomotor membrane. Even although
      clinoid segment aneurysms represent a common incidental finding in magnetic
      resonance studies, its prevalence has not been yet reported. OBJECTIVE: To
      determine the prevalence of incidental clinoid segment saccular aneurysms
      diagnosed by magnetic resonance imaging as well as their anatomic architecture
      and their association with smoking, arterial hypertension, age, and sex of
      patients. METHODS: A total of 500 patients were prospectively studied with
      magnetic resonance imaging time-of-flight sequence and angioresonance with
      contrast material, to search for incidental saccular intracranial aneurysms. The
      site of primary interest was the clinoid segment, but the presence of aneurysms
      in any other location was determined for comparison. The relation among the
      presence of clinoid segment aneurysms, demographic factors, and secondary
      diagnosis of arterial hypertension, smoking, and other vascular/neoplastic
      cerebral lesions was analyzed. RESULTS: We found a global prevalence of
      incidental aneurysms of 7% (95% confidence interval, 5-9), with a prevalence of
      clinoid segment aneurysms of 3% (95% confidence interval, 2-4). Univariate
      logistic regression analysis showed a statistically significant relationship
      among incidental aneurysms, systemic arterial hypertension (P = 0.000), and
      smoking (P = 0.004). CONCLUSIONS: In the studied population, incidental clinoid
      segment aneurysms constitute the variety with highest prevalence.

PMID- 29656154
TI  - Acute Recanalization of a Partially Thrombosed Large Intracranial Aneurysm.
AB  - BACKGROUND: Thrombosed large intracranial aneurysms (TLIAs) are not continuously
      contemplated as stable lesions. Spontaneous recanalization of completely occluded
      large intracranial aneurysms has been described previously. CASE DESCRIPTION: We
      report a middle-aged patient presenting with agitation, acute headache, visual
      field defects, and left hemiparesis. A large thrombosed posterior communicating
      (PCom) artery aneurysm was identified with an infarct at the same arterial
      territory on neuroimaging studies. Digital subtraction angiography (DSA)
      performed 1 week later demonstrated complete recanalization of the TLIA. It was
      treated endovascularly with coils. The patient returned several days later with
      augmenting headaches due to quadrigeminal system subarachnoid hemorrhage. Repeat
      DSA showed filling of the coiled aneurysm from the internal carotid artery
      injection. The PCom artery was catheterized and deconstructed. The patient was
      discharged to home with no additional neurologic deficits. CONCLUSIONS: TLIAs are
      insidious vascular lesions. They can cause nerve or vessel damage by a mass
      effect or through ischemic stroke by emitting emboli into distal vasculature. We
      advise close periodic radiologic follow-up for TLIAs.

PMID- 29656155
TI  - Enhancing photocatalytic activities of titanium dioxide via well-dispersed copper
      nanoparticles.
AB  - The modification of titanium dioxide (TiO2) using noble metal nanoparticles is
      considered as a promising technique to make electrode with outstanding
      photocatalytic performance. In this paper, self-organized anodic TiO2 nanotube
      arrays were decorated with well-distributed small Cu nanoparticles through a
      novel technique that combines magnetron sputtering and thermal dewetting. The
      obtained nanocomposite catalyst exhibited 4-fold increase in the photodegradation
      rate of methylene blue aqueous solution under solar light irradiation than
      anatase TiO2 prepared with same anodization conditions. The enhanced
      photocatalytic activity was attributed to the synergistic effect of Schottky
      barrier and Surface plasmon resonance. The influence of post annealing process,
      sputtering time and thermal dewetting temperature on photocatalytic performance
      was studied and the optimal preparation conditions were proposed. The results of
      this study may provide a new strategy to improve photocatalytic efficiency of
      TiO2 without using high-cost noble metals.

PMID- 29656156
TI  - Ammonia sensing by closely packed WO3 microspheres with oxygen vacancies.
AB  - Ammonia (NH3), is a precursor for the formation of atmospheric fine particulate
      matter (PM2.5), and thus establishing efficient and cost-effective methods to
      detect ammonia emission is highly desired. Transition metal oxide semiconductors
      based sensors for electrochemical gas sensing have been extensively explored.
      Among various types of semiconductors, tungsten oxide (WO3) possesses an
      anisotropic layered crystalline structure and is recognized as a promising
      material for gas sensing. However, the performance of commercial WO3 is
      unsatisfactory because of its high impedance and low charge transportation
      efficiency. Thus, the modification of commercial WO3 is needed to make it an
      efficient ammonia sensor material. In this work, closely packed WO3 microspheres
      with oxygen vacancies were synthesized successfully through a novel two-step
      hydrothermal route. Our WO3 showed a good selectivity to ammonia sensing, and its
      response intensity was 2.6 times higher than that of commercial WO3 because of
      its optimized conductivity. Moreover, the mechanism behind its robust ammonia
      sensing performance was elucidated. The effectiveness of the as-prepared WO3
      microspheres for ammonia sensing also suggests a new strategy for modifying
      transition metal oxide materials.

PMID- 29656157
TI  - Simultaneous enantiomeric analysis of eight pesticides in soils and river
      sediments by chiral liquid chromatography-tandem mass spectrometry.
AB  - A rapid and sensitive multi-residue method was developed for the simultaneous
      quantification of eight chiral pesticides (including diniconazole, metalaxyl,
      paclobutrazol, epoxiconazole, myclobutanil, hexaconazole, napropamide and
      isocarbophos) at enantiomeric levels in environmental soils and sediments using
      chiral liquid chromatography-tandem mass spectrometry based on a combined
      pretreatment of matrix solid-phase dispersion and dispersive liquid-liquid
      microextraction (MSPD-DLLME). Under optimized conditions, 0.1 g of solid sample
      was dispersed with 0.4 g of C18-bonded silica sorbent, and 3 mL of methanol was
      used for eluting the analytes. The collected eluant was dried and then further
      purified by DLLME with 550 MUL of dichloromethane and 960 MUL of acetonitrile as
      extraction and disperser solvent, respectively. The established method was
      validated and found to be linear, precise, and accurate over the concentration
      range of 2-500 ng g-1 for epoxiconazole, paclobutrazol and metalaxyl and 4-500 ng
      g-1 for isocarbophos, hexaconazole, myclobutanil, diniconazole and napropamide.
      Recoveries of sixteen enantiomers varied from 87.0 to 104.1% and the relative
      standard deviations (RSD) were less than 10.1%. Method detection and
      quantification limits (MDLs and MQLs) varied from 0.22 to 1.54 ng g-1 and from
      0.91 to 4.00 ng g-1, respectively. Finally, the method was successfully applied
      to analyze the enantiomeric composition of the eight chiral pesticides in
      environmental solid matrices, which will help better understand the behavior of
      individual enantiomer and make accurate risk assessment on the ecosystem.

PMID- 29656158
TI  - Toxicogenetic study of omeprazole and the modulatory effects of retinol palmitate
      and ascorbic acid on Allium cepa.
AB  - Omeprazole (OME) is a proton pump inhibitor used for the treatment of various
      gastric and intestinal disease; however, studies on its effects on the genetic
      materials are still restricted. The present study aimed to evaluate possible
      toxicogenic effects of OME in Allium cepa meristems with the application of
      cytogenetic biomarkers for DNA damage, mutagenic, toxic and cytotoxic effects.
      Additionally, retinol palmitate (RP) and ascorbic acid (AA) were also co-treated
      with OME to evaluate possible modulatory effects of OME-induced cytogenetic
      damages. OME was tested at 10, 20 and 40 MUg/mL, while RP and AA at 55 MUg/mL and
      352.2 MUg/mL, respectively. Copper sulphate (0.6 MUg/mL) and dechlorinated water
      were used as positive control and negative control, respectively. The results
      suggest that OME induced genotoxicity and mutagenicity in A. cepa at all tested
      concentrations. It was noted that cotreatment of OME with the antioxidant
      vitamins RP and/or AA significantly (p < 0.05) inhibited and/or modulated all
      toxicogenic damages induced by OME. These observations demonstrate their
      antigenotoxic, antimutagenic, antitoxic and anticitotoxic effects in A. cepa.
      This study indicates that application of antioxidants may be useful tools to
      overcome OME-induced toxic effects.

PMID- 29656159
TI  - Effect of Bisphenol A on the extremophilic microalgal strain Picocystis sp.
      (Chlorophyta) and its high BPA removal ability.
AB  - Bisphenol A (BPA) effects and removal by an alkaliphilic chlorophyta, Picocystis,
      were assessed. BPA at low concentrations (0-25 mg L-1) did not inhibit the
      Picocystis growth and photosynthesis during 5 days of exposure. At higher BPA
      concentrations (50 and 75 mg L-1), the growth inhibition did not exceed 43%. The
      net photosynthetic activity was dramatically reduced at high BPA concentrations
      while, the PSII activity was less affected. The exposure to increasing BPA
      concentrations induced an oxidative stress in Picocystis cells, as evidenced by
      increased malondialdehyde content and the over-expression of antioxidant
      activities (ascorbate peroxydase, gluthation-S-transferase and catalase).
      Picocystis exhibited high BPA removal efficiency, reaching 72% and 40% at 25 and
      75 mg L-1 BPA. BPA removal was ensured mainly by biodegradation/biotransformation
      processes. Based on these results, the extended tolerance and the high removal
      ability of Picocystis make her a promising specie for use in BPA bioremediation.

PMID- 29656160
TI  - Comprehensive transcriptome profiling of soybean leaves in response to simulated
      acid rain.
AB  - As a source of edible oil and protein, soybean is a major globally important
      economic crop; Improving its production has been an important objective of
      soybean breeding. Acid rain has been shown to influence soybean growth and
      productivity, with consequent adverse impacts on its production for use by human
      populations. In this study, RNA sequencing technology was utilized to examine
      changes in gene expression when soybean was exposed to simulated acid rain (SAR).
      We sampled soybean leaves at five time intervals (0, 6, 30, 54, 78, and 102 h),
      and built the cDNA library. In total, 54,175 expression genes were found,
      including 2016 genes with differential expression. A total of 416 genes were
      considered, as they were closely related to the response to SAR. Genes related to
      the regulation of sulfur and nitrogen metabolism, carbohydrate metabolism,
      photosynthesis, and reactive oxygen species were among those differentially
      expressed in response to SAR. In this study, we examined the response mechanisms
      of soybean under SAR exposure. Our findings will improve our understanding of the
      molecular mechanisms employed by soybean in responding to abiotic stress, and
      therefore provides important information in developing soybean breeding to
      improve tolerance to these stresses.

PMID- 29656161
TI  - Migration and health risks of nonylphenol and bisphenol a in soil-winter wheat
      systems with long-term reclaimed water irrigation.
AB  - Reclaimed water reuse has become an important means of alleviating agricultural
      water shortage worldwide. However, the presence of endocrine disrupters has
      roused up considerable attention. Barrel test in farmland was conducted to
      investigate the migration of nonylphenol (NP) and bisphenol A (BPA) in soil
      winter wheat system simulating reclaimed water irrigation. Additionally, the
      health risks on humans were assessed based on US EPA risk assessment model. The
      migration of NP and BPA decreased from the soil to the winter wheat; the
      biological concentration factors (BCFs) of NP and BPA in roots, stems, leaves,
      and grains all decreased with their added concentrations in soils. The BCFs of NP
      and BPA in roots were greatest (0.60-5.80 and 0.063-1.45, respectively). The
      average BCFs of NP and BPA in winter wheat showed negative exponential relations
      to their concentrations in soil. The amounts of NP and BPA in soil-winter wheat
      system accounted for 8.99-28.24% and 2.35-4.95%, respectively, of the initial
      amounts added into the soils. The hazard quotient (HQ) for children and adults
      ranged between 10-6 and 1, so carcinogenic risks could be induced by ingesting
      winter wheat grains under long-term reclaimed water irrigation.

PMID- 29656163
TI  - Myofibrilar functional dysregulation in fish: A new biomarker of damage to
      pesticides.
AB  - Endosulfan (ES) modifies the ultrastructure of skeletal muscle fibers and causes
      changes to the swimming behavior of fish. The objectives of the present work were
      to evaluate, in fishes of Australoheros facetus, 1) the integrity of myofibrils
      (Mf) by the analysis of SDS-PAGE profiles, and 2) the functionality of Mf through
      the microscopically monitoring of the contraction and changes in Mg2+ Ca2+-
      ATPase and Mg2+(EGTA) -ATPase activities. As expected, after the addition of the
      contraction buffer, control fish Mf contracted. On the contrary, Mf from fish
      exposed at 0.5 MUg/L ES showed a partial contraction and none of the fish exposed
      at 10 MUg/L ES contracted. As judged by its high Mg2+ Ca2+ ATPase activity and
      low Mg2+ (EGTA) ATPase activity, control Mf showed good functionality. In Mf from
      fish exposed to 0.5 and 10 MUg/L ES the activities of these enzymes were similar,
      suggesting denaturation or degradation of some component of tropomyosin-troponin
      complex. SDS-PAGE patterns of Mf from fish exposed to ES showed degradation of
      the myosin heavy chain and of tropomyosin. Similar values of lipid peroxidation
      (TBARS) were found in both control and exposed Mf, suggesting that lipid
      oxidation was not be related to the above-mentioned changes. The observed effects
      expand the knowledge of ES action in muscles and could be used as biomarkers of
      damage in fishes exposed to organochlorine compounds like the insecticide
      endosulfan.

PMID- 29656162
TI  - Effects of kinetin on plant growth and chloroplast ultrastructure of two Pteris
      species under arsenate stress.
AB  - Cytokinins (CTKs) are effective in alleviating abiotic stresses on plants, but
      little information is available regarding the effects of CTKs on arsenic (As)
      accumulation and changes of chloroplast ultrastructure in plants with different
      As-accumulating ability. Here a hydroponic experiment was designed to evaluate
      the effects of different concentration of kinetin (KT, 0-40 mg/L) on growth and
      chloroplast ultrastructure of As hyperaccumulator Pteris cretica var. nervosa and
      non-hyperaccumulator Pteris ensiformis treated by 5 mg/L arsenate for 14 days.
      The growth parameters, As accumulation, contents of photosynthetic pigments and
      chloroplast ultrastructure were examined. The results showed that KT promoted the
      growth of two plants, and significantly increased As accumulation and
      translocation in P. cretica var. nervosa and P. ensiformis at 5 and 20 mg/L,
      respectively. Additionally, the contents of chlorophyll a and carotenoid in two
      plants showed no significant difference at 20 mg/L KT compared to the control.
      Chloroplast ultrastructure of P. cretica var. nervosa was integral with KT
      application. Comparatively, the swollen chloroplasts were increased, plasmolysis
      appeared, and chloroplast grana slice layers and stroma lamellas were clearly
      separated or distorted at 5 mg/L KT in P. ensiformis. The length and width of
      chloroplasts in P. cretica var. nervosa were significantly increased with KT
      addition compared to the control. However, the length of chloroplasts in P.
      ensiformis was significantly decreased but their width showed no significant
      change. Furthermore, the deterioration of chloroplast ultrastructure in P.
      ensiformis was ameliorated by 40 mg/L KT. These results suggested that KT
      increased As accumulation and was beneficial to maintain the photosynthetic
      pigments for a good growth of plants. Therefore, KT could maintain and reorganize
      the ultrastructure integrality of As-stressed chloroplasts to some extent for the
      two plants, especially at high concentration.

PMID- 29656164
TI  - Lignolytic mushroom Lenzites elegans WDP2: Laccase production, characterization,
      and bioremediation of synthetic dyes.
AB  - A mycoremedial study was undertaken for decolourization of synthetic dyes using
      wood rot fungal culture Lenzites elegans WDP2. The culture was isolated from
      decaying wood as fruiting body, and identified on the basis of 5.8S ITS rRNA gene
      sequence analysis. Qualitative plate screening of culture showed extracellular
      laccase and lignin peroxidase production, while only laccase enzyme was produced
      in higher amount (156.793 Uml-1) in minimal salt broth medium containing glucose
      and veratryl alcohol. Laccase activity was increased up to 189.25 Uml-1 after
      optimization of laccase production by optimization of one variable at a time
      approach. Molecular characterization of laccase enzyme was done using SDS PAGE
      and Native PAGE based isozyme analyses. The culture was able to decolorize three
      synthetic dying compounds (congo red, Malachite green and brilliant green) in
      broth media, while showed very less decolourization in plate assay. The fungal
      culture varied in their dye decolourizing potential in broth culture, showing
      92.77%, 21.27% and 98.8% maximum decolourization of brilliant green, malachite
      green and congo red respectively. The congo red dye was completely bio-absorbed
      by fungal culture within one month. The fungal decolourized broth also revealed
      the extracellular laccase activity; varied from 10 Uml-1 to 68.5 Uml-1 in all the
      three cases, supports the involvement of laccase enzyme in decolorization. Phase
      contrast microscopy clearly revealed bio-sorption of the dyes by fungal culture
      into the mycelium/spores in the photomicrographs.

PMID- 29656165
TI  - Effect of elevated ozone and varying levels of soil nitrogen in two wheat
      (Triticum aestivum L.) cultivars: Growth, gas-exchange, antioxidant status, grain
      yield and quality.
AB  - Tropospheric ozone (O3) is a phytotoxic air pollutant causing a substantial
      damage to plants and agriculture worldwide. Plant productivity is affected by
      several environmental factors, which interact with each other. Studies related to
      interactions involving O3 and different levels of nitrogen (N) are still rare and
      elusive. In the present study we grew two wheat cultivars (HD2967 and Sonalika)
      in open top chambers (OTC) under ambient (AO) and elevated O3 (EO) (ambient + 20
      ppb O3) and provided two levels of N fertilization; (a) recommended nitrogen
      (RN), (b) 1.5 times the recommended N (HN). Growth (root/shoot ratio, leaf number
      and leaf area), biomass, gas-exchange (stomatal conductance (gs), photosynthesis
      (A), transpiration (E), chlorophyll fluorescence (Fv/Fm), physiological
      (chlorophyll and carotenoids), biochemical [antioxidant activity, lipid
      peroxidation (MDA)] parameters and leaf N content were measured at the vegetative
      and reproductive phases. Yield attributes (spike weight plant-1, grain weight
      plant-1, grain numbers plant-1, husk weight plant-1, straw weight plant-1, 1000
      grain weight, harvest index) and seed N content were analyzed at the final
      harvest stage. Grain yield plant-1 was decreased in Sonalika under EO
      irrespective of different levels of N fertilization. Seed N content decreased by
      3.9% and 5.6% in HD2967 and Sonalika, respectively, under EO at RN treatment.
      Antioxidant defense played an important role in protecting the plants against O3
      stress which was enhanced under HN treatment. Response of antioxidants varied
      between the cultivar, growth phase (at the vegetative or reproductive phase) and
      the N levels (RN or HN). Cultivar HD2967 was characterized by higher biomass, gs
      and stronger antioxidant protection system, while, Sonalika showed early
      senescence response (decreased leaf number plant-1, gs) and greater resources
      allocation towards eco-physiological parameters (increased A and Fv/Fm) at the
      vegetative phase, resulting in the significant decrease in the yield attributes.
      Further study warrants the need to screen a large number of cultivars in relation
      to their response to various levels of N fertilization to minimize the yield
      losses under highly O3 polluted areas.

PMID- 29656166
TI  - Identification of molt-inhibiting hormone and ecdysteroid receptor cDNA sequences
      in Gammarus pulex, and variations after endocrine disruptor exposures.
AB  - In amphipods, growth, development and reproduction are mediated by the molt,
      which is a hormonally controlled process and which, therefore, could be impacted
      by endocrine disruption compounds (EDC). The molt process is controlled by both X
      organ (XO) and Y-organ (YO) through a variety of hormones and receptors including
      the molt-inhibiting hormone (MIH) and the ecdysteroid receptor (EcR). However,
      although many studies were devoted to characterize MIH and EcR in crustaceans,
      only few works evaluated their variations under EDCs exposures. Consequently, the
      present work aimed to characterize MIH and EcR genes of the amphipod Gammarus
      pulex, as well as to study their relative expression variations after exposure to
      four EDCs, proved in vertebrates: ethinylestradiol (estrogen), 4-hydroxytamoxifen
      (anti-estrogen), 17alpha-methyltestosterone (androgen) and cyproterone acetate
      (anti-androgen). PCR amplification allowed to obtain 204 bp length and 255 bp
      length fragments, encoding for partial sequences of 68 amino acids and 85 amino
      acids, which correspond to EcR and MIH, respectively, and which are highly
      conserved in crustacean species. Results highlighted MIH and EcR expressions
      mainly in G. pulex head, which is the localization of XO and YO. Moreover,
      irrespective of the EDC exposure, increases of MIH and EcR relative expressions
      were observed, as it was observed after the exposure to 20-hydroxyecdysone
      (20HE), the natural molt hormone, used as positive control. Therefore, it
      appeared that tested EDCs behaved like 20HE, suggesting that their effects could
      occur through the ecdysteroids pathways, and so impact the molt process of G.
      pulex on the long term. Finally, the present study is a first step in the
      possibility of using MIH and EcR relative expressions as biomarkers of exposure
      for EDCs risk assessment. However additional studies must first be carried out to
      better characterize and understand their variations, and also better predicted
      consequences for the exposed amphipods.

PMID- 29656167
TI  - Extracellular vesicles exposing tissue factor for the prediction of venous
      thromboembolism in patients with cancer: A prospective cohort study.
AB  - INTRODUCTION: The procoagulant activity of extracellular vesicles (EV) exposing
      tissue factor (TF) is a promising biomarker for venous thromboembolism (VTE) in
      cancer patients. We evaluated an in-house EV-TF activity assay (the fibrin
      generation test) for the prediction of cancer-associated VTE. We also compared
      the results with the fibrin generation tests to an EV-TF-dependent factor Xa
      generation assay in samples from pancreatic cancer patients. MATERIALS AND
      METHODS: Data collected in a multinational, prospective cohort study were used.
      Patients with various types of advanced cancer were enrolled if chemotherapy was
      scheduled or started in the previous 3 months. Patients were followed for 6
      months for the occurrence of VTE. The fibrin generation test was performed at
      baseline to measure EV-TF procoagulant activity. RESULTS: The fibrin generation
      test was performed in 648 patients with advanced cancer. The mean age was 62
      years; 58% had distant metastasis. Forty patients (6.1%) developed VTE. Overall,
      a high fibrin generation test result was associated with a two-fold increased
      risk for VTE (HR 2.0; 95%-CI, 1.1-3.6). The association was stronger in patients
      with pancreatic cancer (HR 4.1; 95%-CI, 0.91-19) than in those with other tumor
      types (HR 1.5; 95%-CI, 0.72-3.1). Correlation between the FGT and the TF
      dependent factor Xa generation assay in patients with pancreatic cancer was poor
      (Spearman's R = 0.35). CONCLUSION: This study shows that a high EV-TF
      procoagulant activity as measured by the fibrin generation test is associated
      with an increased risk of VTE in cancer patients, in particular in those with
      pancreatic cancer. Future studies should aim to further improve the feasibility
      and accuracy of EV-TF activity assays.

PMID- 29656168
TI  - A novel allele variant of the SERPINF2 gene responsible for severe plasmin
      inhibitor (alpha2-antiplasmin) deficiency in an Italian patient.

PMID- 29656169
TI  - International, multicenter evaluation of a new D-dimer assay for the exclusion of
      venous thromboembolism using standard and age-adjusted cut-offs.
AB  - INTRODUCTION: We sought to determine the test characteristics of an automated
      INNOVANCE D-dimer assay for the exclusion of pulmonary embolism (PE) and deep
      venous thrombosis (DVT) in emergency department (ED) patients using standard and
      age-adjusted cut-offs. METHODS: Cross-sectional, international, multicenter study
      of consecutive patients with suspected DVT or PE in 24 centers (18 USA, 6
      Europe). Evaluated patients had low or intermediate Wells PE or DVT scores. For
      the standard cut-off, a D-dimer result <500 ng/ml was negative. For the age
      adjusted cut-off, we used the formula: Age (years) * 10. The diagnostic standard
      was imaging demonstrating PE or DVT within 3 months. We calculated test
      characteristics using standard methods. We also explored modifications of the age
      adjustment multiplier. RESULTS: We included 3837 patients and excluded 251. The
      mean age of patients evaluated for PE (n = 1834) was 48 +/- 16 years, with 676
      (37%) male, and 1081 (59%) white. The mean age of evaluated for DVT (n = 1752)
      was 53 +/- 16 years, with 710 (41%) male, and 1172 (67%) white. D-dimer test
      characteristics for PE were: sensitivity 98.0%, specificity 55.4%, negative
      predictive value (NPV) 99.8%, positive predictive value (PPV) 11.4%, and for DVT
      were: sensitivity 92.0%, specificity 44.8%, NPV 98.8%, PPV 10.3%. Age adjustment
      increased specificity (59.6% [PE], 51.1% [DVT]), but increasing the age
      adjustment multiplier decreased sensitivity without increasing specificity.
      CONCLUSIONS: INNOVANCE D-dimer is highly sensitive and can exclude PE and DVT in
      ED patients with low- and intermediate- pre-test probability. Age-adjustment
      increases specificity, without increasing false negatives.

PMID- 29656170
TI  - Iranian women's experiences of dealing with the complexities of an unplanned
      pregnancy: A qualitative study.
AB  - OBJECTIVE: The aim of this study was to explore women's experiences of dealing
      with the complexities of an unplanned pregnancy. DESIGN: Qualitative content
      analysis was used to analyse the reports of women experiencing unplanned
      pregnancy and provide meaning to the results. SETTING: Participants from Tabriz,
      Iran were recruited using purposive sampling method from June to September 2016.
      PARTICIPANTS: Data were gathered using face to face unstructured interviews among
      23 women between the ages of 18-48 who recently reported having experienced an
      unplanned pregnancy. FINDINGS: Outcomes of the data analysis yielded the
      formation of four distinct themes; disbelief and negative affective responses,
      fragile justification, perceived supports and post-decision dissonance. KEY
      CONCLUSIONS: The majority of women, reported that the emotional effects of
      unplanned pregnancy represented the greatest challenge. This was described as
      occurring not just immediately after pregnancy recognition, but throughout the
      course of decision making and selected course of action. IMPLICATIONS FOR
      PRACTICE: The findings of this study indicate the need for essential counselling
      services and supportive care for women experiencing an unplanned pregnancy.

PMID- 29656172
TI  - Factors affecting child development assessed by the Ages and Stages Questionnaire
      (ASQ) in an Arabic speaking population.

PMID- 29656173
TI  - Factors associated with extension of the scheduled time for spine surgery.
AB  - OBJECTIVES: Adherence to scheduled times in surgery is important in hospital
      management. However, sudden surgical changes or unexpected intraoperative
      problems may lead to prolongation of operative times. The purpose of this study
      was to investigate operative times in spinal surgery and to identify causes of
      delays during surgery. PATIENTS AND METHODS: A retrospective review of 488 cases
      of spinal surgery was performed to investigate operations prolonged for >2 h and
      to identify factors associated with prolongation. RESULTS: There were 250 cases
      without a delay, and 144, 64, and 30 with delays of <1 h, 1-2 h, and >2 h,
      respectively. Delays >2 h were caused by interruptions due to loss of
      transcranial motor-evoked potential (Tc-MEP) signals in spinal cord monitoring (n
      = 15), reinsertion due to screw misplacement (n = 5), intraoperative pathology
      procedures (n = 5), extension of fusion range with instrumentation (n = 3), and
      complete resection of an intramedullary tumor (n = 2). Surgeries with delays >2 h
      (n = 30) had greater rates of scheduled surgery for >5 h (40% vs. 23%; P < 0.05),
      instrumentation use (70% vs. 47%; P < 0.05), reoperation (33% vs. 7%; P < 0.01%),
      and estimated blood loss (EBL) (1573 vs. 435 ml; P < 0.01), compared to all other
      surgeries (n = 458). In multivariate logistic regression, reoperation (HR 3.15,
      95% CI 1.52-6.55; p < 0.01) and EBL >= 1000 ml (HR 3.35, 95% CI 1.56-7.18; p <
      0.01) were significantly associated with prolongation of surgery by >2 h.
      CONCLUSION: Information suggesting potential prolongation of surgery should be
      shared with all medical staff. Reliable surgical techniques and hemostasis may
      also reduce delays in surgery.

PMID- 29656171
TI  - Associations between birth size and later height from infancy through adulthood:
      An individual based pooled analysis of 28 twin cohorts participating in the
      CODATwins project.
AB  - BACKGROUND: There is evidence that birth size is positively associated with
      height in later life, but it remains unclear whether this is explained by genetic
      factors or the intrauterine environment. AIM: To analyze the associations of
      birth weight, length and ponderal index with height from infancy through
      adulthood within mono- and dizygotic twin pairs, which provides insights into the
      role of genetic and environmental individual-specific factors. METHODS: This
      study is based on the data from 28 twin cohorts in 17 countries. The pooled data
      included 41,852 complete twin pairs (55% monozygotic and 45% same-sex dizygotic)
      with information on birth weight and a total of 112,409 paired height
      measurements at ages ranging from 1 to 69 years. Birth length was available for
      19,881 complete twin pairs, with a total of 72,692 paired height measurements.
      The association between birth size and later height was analyzed at both the
      individual and within-pair level by linear regression analyses. RESULTS: Within
      twin pairs, regression coefficients showed that a 1-kg increase in birth weight
      and a 1-cm increase in birth length were associated with 1.14-4.25 cm and 0.18
      0.90 cm taller height, respectively. The magnitude of the associations was
      generally greater within dizygotic than within monozygotic twin pairs, and this
      difference between zygosities was more pronounced for birth length. CONCLUSION:
      Both genetic and individual-specific environmental factors play a role in the
      association between birth size and later height from infancy to adulthood, with a
      larger role for genetics in the association with birth length than with birth
      weight.

PMID- 29656174
TI  - Multiplanar realignment for unstable Hangman's fracture with Posterior C2-3
      fusion: A prospective series.
AB  - OBJECTIVE: There is lack of consensus on the preferred approach for unstable
      Hangman's fracture. The associated soft tissue injuries apart from apparent bony
      injury add to the complexity of dislocation and needs to be addressed. Here, we
      evaluated the clinico-radiological characteristics and outcome of patients
      managed by posterior C2-3 fusion. PATIENTS & METHODS: Nine patients with unstable
      Hangman's fracture (type II and IIA) were prospectively studied. The displacement
      of fractured fragments and C2-3 dislocation was studied in multiple planes. C2
      pars-pedicle screw was placed to bring fractured fragments together (lag effect),
      which was then fused with C3 lateral masses to achieve multiplanar realignment.
      Clinical outcome was assessed in terms of pain (VAS score) and neurological
      status after surgery. Patient's clinico-radiological status was followed up at
      regular intervals. RESULTS: Pain was the predominant symptom (VAS: 8.1 +/- 1.1).
      Only one had neurological deficit (ASIA- D). Mean VAS score improved
      significantly in postoperative period (1.2 +/- 1.6). About two-third (66.7%) had
      atypical Hangman's. In six, fractured segments were malaligned in multiple
      planes. Axial rotation, lateral translation and superior translation (over
      riding) of fragments were seen in 4, 4 and 3 patients respectively. Two had
      adjacent level injuries. Reduction and realignment of fractured fragments as well
      as C2-3 in multiple planes could be achieved in all. Follow-up varied from 6 to
      22 months (mean, 12.8 +/- 5.7). Bony fusion was evident in 9 to 12 months. Three
      patients showed mild curvature change in subaxial spine. CONCLUSION: The
      fractures fragments may be dislocated in axial (rotation and lateral translation)
      apart from antero-posterior plane. It is important to study the radiology in
      various planes. Posterior C2-3 fusion is an effective way to achieve good
      realignment of bony fragments in all planes. It also addresses the instability
      resulting from soft tissue injury.

PMID- 29656175
TI  - Distribution of environmental tritium in rivers, groundwater, mine water and
      precipitation in Goa, India.
AB  - Tritium concentration in rivers, groundwater, precipitation and mine pits water,
      all over Goa state was characterized to find out spatial and temporal variability
      of tritium. Twenty four water samples were collected during pre-monsoon and post
      monsoon and analyzed for their tritium concentration. The mean tritium
      concentration in surface and sub-surface hydrosphere is 2.5 (+/-0.6) TU. The mean
      concentration of tritium in rivers, groundwater, mines pits water and rain water
      are 2.9 (+/-0.5) TU, 1.95 (+/-0.5) TU, 2.5(+/-0.3) TU and 3.1(+/-0.1) TU
      respectively. The tritium distribution in all the samples shows modern
      precipitation (post-1950) component in surface and sub-surface hydrosphere of
      Goa. The HYSPLIT4.0 air mass trajectory model and atmospheric circulation pattern
      suggest that the moisture origin was from the Arabian Sea and this low tritium
      moisture is diluting the tritium concentration of surface hydrosphere near the
      coastal area. The tritium concentration in surface hydrosphere shows more and
      more enrichment as one move inland (i.e. away from the coast). Significant
      seasonal change is observed in the surface hydrosphere. The pre-monsoon samples
      showed higher tritium concentration than post-monsoon samples. This may be due to
      high rate of re-evaporation of water and a reduction in the supply of oceanic
      moisture during the summer (pre-monsoon).

PMID- 29656176
TI  - Underreporting of fatal poisonings in Brazil - A descriptive study using data
      from four information systems.
AB  - Poisoning is a worldwide problem that involves individuals of all ages and a
      range of chemicals. In this study, fatal poisoning cases that occurred in the
      Federal District of Brazil (DF) from 2009 to 2013 were described using
      information from four systems, and the reasons for underreporting of each system
      were discussed. Data were obtained from the mortality information system (SIM),
      the notifiable disease information system (SINAN), the poison information center
      (CIT), and the forensic medicine institute (IML) of the DF. In total, 288 cases
      were reported to SIM, 18 to SINAN, 29 to CIT and 101 cases identified in the IML.
      SIM data indicated a prevalence of 2.24 cases/year/100,000 individuals in the DF,
      higher than the national estimation (1.36). After eliminating the 98 duplicate
      cases among the systems, 338 fatal unique cases were identified, from which 74.0%
      were reported in only one system (mainly the SIM), 23.4% in two systems, 8 cases
      in three systems and only 1 case was reported in the four systems. Over two
      thirds of the 338 fatalities involved men (67.4%), and 46.9% involved individuals
      aged 20-39 years. Medications were the main agent involved (49.4%), followed by
      pesticides (29.9%). The fatalities occurred mainly after unintentional exposure
      (50.8%) and suicide (47.7%, of which 53.5% involved pesticides). These results
      confirmed the previous hypothesis that none of the information systems could
      capture the whole picture of fatal poisonings in the DF. Underreporting was found
      in all systems, indicating the need to improve the information quality and the
      coordination of data reporting, so that health authorities can better understand
      and reduce these fatalities.

PMID- 29656177
TI  - Contribution of Raman and Surface Enhanced Raman Spectroscopy (SERS) to the
      analysis of vehicle headlights: Dye(s) characterization.
AB  - Although ubiquitous on accident scenes, the polymers from headlight optics are
      often neglected in hit-and-run cases, and their evidential value restrained to
      direct comparison once a corresponding vehicle is found. Multilayered automotive
      paint fragments are preferred for their access to corresponding databases (PDQ,
      EUCAP) to infer models and brands of cars. The potential of polymers headlights
      for providing forensic intelligence has never been exploited, principally due to
      the lack of diversity, of appropriate databases, and of case examples. The
      motives are very simple however. Headlight polymers suffer from a lack of
      differentiation, and about 90% of them are composed of polymethylmethacrylate
      (PMMA). The discriminating powers using techniques in sequence typically range
      from 30 to 60%. In this paper, we take advantage of the extreme sensitivity of
      Surface Enhanced Raman Spectroscopy (SERS) to analyze the dye composition of the
      polymer headlights. The measurements by standard Raman spectroscopy at 488, 633,
      and 785nm permits us to identify the polymer type with relative ease. 51 out of
      53 samples are composed of PMMA, the two remaining being either Polycarbonate or
      Polybutylene terephthalate. Additionally, using SERS with silver colloids at 488
      and 633nm, provides enhanced spectra of the dyes used in the composition with an
      extreme sensitivity and specificity. With SERS we are able to differentiate the
      majority of the headlights with a remarkable 90-100% discriminating power.
      Solvent Orange 60, Solvent Red 52 and Solvent Red 111 were successfully
      identified as dyes used in the manufacture of the headlights. These results
      demonstrate that a combined Raman-SERS approach has the potential to replace an
      otherwise lengthy sequence of many different analytical techniques. With one
      single instrument, we offer the possibility to combine an analysis of the polymer
      type, and of the dye components with high discriminating capabilities. These
      results open up new opportunities for exploiting headlight plastics in road
      accidents investigations. It has the potential to help in source attribution,
      and/or database building in a forensic intelligence perspective.

PMID- 29656178
TI  - Generation of 3 spinocerebellar ataxia type 1 (SCA1) patient-derived induced
      pluripotent stem cell lines LUMCi002-A, B, and C and 2 unaffected sibling control
      induced pluripotent stem cell lines LUMCi003-A and B.
AB  - Spinocerebellar ataxia type 1 (SCA1) is a hereditary neurodegenerative disease
      caused by a CAG repeat expansion in exon 8 of the ATXN1 gene. We generated
      induced pluripotent stem cells (hiPSCs) from a SCA1 patient and his non-affected
      sister by using non-integrating Sendai Viruses (SeV). The resulting hiPSCs are
      SeVfree, express pluripotency markers, display a normal karyotype, retain the
      mutation (length of the CAG repeat expansion in the ATXN1 gene) and are able to
      differentiate into the three germ layers in vitro.

PMID- 29656180
TI  - Peptide modification and cyclization via transition-metal catalysis.
AB  - Transition-metal catalysis has unlocked new paradigms for the late-stage
      modification and cyclization of peptides by harnessing the innate reactivity of
      proteinogenic amino acids. The field is rapidly evolving, with recent advances
      encompassing three fundamental areas-heteroatom couplings, decarboxylative cross
      couplings, and C-H functionalizations-which have markedly extended the scope of
      conventional peptide modification and bioconjugation strategies. The advances
      outlined herein facilitate access to high-value peptide targets with promising
      applications in materials science and drug discovery.

PMID- 29656179
TI  - Novel reno-protective mechanism of Aspirin involves H2AK119 monoubiquitination
      and Set7 in preventing type 1 diabetic nephropathy.
AB  - BACKGROUND: Even after several novel therapeutic approaches, the number of people
      with diabetic nephropathy (DN) still continues to increase globally, this suggest
      to find novel therapeutic strategies to prevent it completely. Recent reports,
      are indicating the ubiquitin proteasome system alterations in DN. Recently, we
      also showed that, histone H2AK119 mono-ubiquitination (H2AK119-Ub) found to
      regulate Set7, a key epigenetic enzyme in the development of renal fibrosis under
      type 1 diabetic condition. Hence, we aimed to study the role of a known 20s
      proteasome inhibitor Aspirin, on histone ubiquitination in the progression of DN.
      METHODS: Male Wistar rats were rendered diabetic using a single dose of
      Streptozotocin (55mgkg-1, ip). After 4 weeks, diabetic animals were grouped into
      respective groups and the drug, aspirin, low dose (25mgkg-1day-1), high dose
      (50mgkg-1day-1) was administered through po route. At the end of the study,
      kidneys from all the groups were collected and processed separately for
      glomerular isolation, protein isolation, and for histopathological studies.
      RESULTS: Aspirin administration, reduced the protein expression of Mysm1,
      increased the protein expression of H2AK119-Ub and thereby reduced the Set7
      protein expression in glomeruli isolated from diabetic animals and prevented
      renal fibrosis. CONCLUSIONS: In conclusion, our results are clearly indicating
      that, aspirin prevents renal fibrosis in diabetic animals through decreasing the
      expression of Mysm1, increasing the expression of H2AK119-Ub and thereby
      decreasing the protein expression of Set7, which is a novel mechanism. Moreover,
      this mechanism may lay down a novel strategy to prevent DN completely in future.

PMID- 29656181
TI  - Elevated systemic microbial translocation in pregnant HIV-infected women compared
      to HIV-uninfected women, and its inverse correlations with plasma progesterone
      levels.
AB  - In HIV infection, increased adverse perinatal outcomes reported among HIV
      associated pregnancies are not fully understood. Currently, microbial product
      translocation (MT) from a permeable mucosa is demonstrated as a driver of
      inflammation, and may contribute to preterm delivery in HIV. Here, our results
      showed that plasma LPS levels (a representative marker of MT) were increased in
      HIV-infected women in the first and second trimester. Progesterone levels were
      significantly decreased in HIV-infected subjects in the first trimester and
      second trimester. There were significant inverse correlations between plasma LPS
      and progesterone in the first and second trimester. These results suggested
      heightened systemic MT and decreased plasma progesterone levels in HIV-infected
      pregnant women may play a role in increased incidence of preterm delivery.

PMID- 29656182
TI  - Co-culture of ovarian cancer stem-like cells with macrophages induced SKOV3 cells
      stemness via IL-8/STAT3 signaling.
AB  - Among recent concepts in the cancer biology field, the tumor microenvironment is
      highly associated with cancer stem cells, and plays a key role in tumor
      progression. This study aimed to explore the mechanism that the stemness
      induction of SKOV3 cell line by macrophages derived from THP-1 cells, which was
      co-cultured with SKOV3-derived ovarian cancer stem-like cells (OCSLCs). Sphere
      formation, soft agar colony formation, and expression levels of CD133 and CD44
      were assessed to reflect OCSLC properties. ELISA was used to evaluate secretion
      profile changes in macrophages co-cultured with or without SKOV3-derived OCSLCs.
      For mechanistic evaluation, rhIL-8, IL-8 neutralizing antibody (IL-8 Ab), signal
      transducer and activator of transcription 3 (STAT3) shRNA and STAT3 cDNA were
      used. The results showed that IL-10, VEGF, MMP-9, IL-8 secretion and CD163 and
      STAT3 expression levels in macrophages co-cultured with OCSLCs were increased
      compared with those from THP-1 cells, while IL-12 and NO amounts were
      significantly reduced, reflecting M2 macrophage polarization. Addition of rhIL-8
      to THP-1 cell conditioned media promoted M2 macrophage polarization and stemness
      in SKOV3 cells, which were suppressed by IL-8 Ab addition to co-culture
      conditioned media. Consistently, overexpression of STAT3 induced M2 macrophage
      polarization and stemness in SKOV3 cells, which were inhibited by STAT3 knockdown
      in macrophages from THP-1 cells. Importantly, STAT3 overexpression rescued the
      effects of IL-8 Ab on M2 macrophage polarization and stemness in SKOV3 cells.
      These results suggested that stemness induction in SKOV3 cells by macrophages co
      cultured with SKOV3-derived OCSLCs involved IL-8/STAT3 signaling.

PMID- 29656183
TI  - Hispidulin inhibits hepatocellular carcinoma growth and metastasis through AMPK
      and ERK signaling mediated activation of PPARgamma.
AB  - Hispidulin, a phenolic flavonoid, exerts potent cytotoxicity towards a variety of
      human cancers. However, the effects of hispidulin on hepatocellular carcinoma
      (HCC) and underlying molecular mechanisms of its action remain elusive. The
      present study investigated the effect of hispidulin on HCC in experimental
      models, including tumor cell lines and mouse tumor xenograft. Results
      demonstrated that hispidulin was cytotoxic and anti-proliferative to HCC cell
      lines (SMMC7721 and Bel7402). Hispidulin activated caspase-3 and triggered
      apoptosis in HCC cells. Moreover, hispidulin inhibited cell migration and
      invasion by inhibiting the expression of matrix metalloproteinases (MMP-2, MMP-9)
      and by inducing tissue inhibitor of metalloproteinase-3 (TIMP-3) expression.
      Hispidulin activated peroxisome proliferator-activated receptor gamma (PPARgamma)
      signaling which mainly contributed to its cytotoxicity in HCC cells. Remarkably,
      GW9662 (a PPARgamma inhibitor) or PPARgamma targeting siRNA significantly
      abrogated the anti-proliferative, pro-apoptotic, and anti-metastatic effects of
      hispidulin in HCC cells. Furthermore, hispidulin induced activation of PPARgamma
      which was associated with increased phosphorylation of AMPK, ERK, JNK in HCC
      cells. Compound C (an AMPK inhibitor) or PD98059 (a MEK inhibitor) partly
      reversed the effects of hispidulin on PPARgamma signaling in HCC cells. In
      contrast, no significant changes in PPARgamma signaling were observed in HCC
      cells pretreated with SP600125 (a JNK inhibitor), while SP6000125 significantly
      inhibited the anti-cancer effects of hispidulin in HCC cells. Hispidulin
      administration effectively suppressed Bel7402 xenograft tumor growth and lung
      metastasis in vivo. Our findings indicate that PPARgamma activation by hispidulin
      effectively suppressed HCC cell growth and metastasis both in vitro and in vivo.

PMID- 29656184
TI  - Ropivacaine regulates the expression and function of heme oxygenase-1.
AB  - As a new generation of amide-type local anesthetics (LAs), ropivacaine has been
      widely used for pain management in clinical settings. Increasing evidence has
      shown that administration of ropivacaine causes cytotoxic effects and apoptosis.
      However, the underlying molecular mechanisms still need to be elucidated. In the
      current study, our results indicated that ropivacaine treatment caused a
      significant induction of heme oxygenase-1 (HO-1) at both the mRNA and protein
      levels in human SHSY5Y cells. Levels of HO-1 mRNA and protein peaked at 1 h and
      18 h, respectively, in response to ropivacaine treatment. Additionally,
      ropivacaine treatment enhanced HO-1 activity in a dose-dependent manner.
      Interestingly, we found that ropivacaine treatment induced phosphorylation of
      p38. Blockage of p38 phosphorylation with its specific inhibitor SB203580 or by
      transfection with p38 siRNA restrained ropivacaine-stimulated HO-1 expression.
      Additionally, we found that ropivacaine treatment promoted nuclear translocation
      of Nrf2 and amplified ARE promoter activity. Silencing of Nrf2 abolished
      ropivacaine-induced HO-1 expression. Notably, we found that inhibition of HO-1
      activity promoted ropivacaine-induced production of reactive oxygen species
      (ROS), deletion of reduced glutathione (GSH), and release of lactate
      dehydrogenase (LDH), suggesting that induction of HO-1 by ropivacaine acted as a
      compensatory survival response against ropivacaine.

PMID- 29656185
TI  - Exogenous SERP1 attenuates restenosis by restoring GLP-1 receptor activity in
      diabetic rats following vascular injury.
AB  - The activity of glucagon-like peptide 1 (GLP-1R) is essential for preventing
      restenosis following vascular injury; however, the mechanism of dysfunctional GLP
      1R glycosylation and ways to enhance the activity of GLP-1R on vascular surfaces
      in diabetic patients are poorly understood. In the present study, we investigated
      the N-glycosylation level and role of stress-associated endoplasmic reticulum
      protein 1 (SERP1) in preventing restenosis following carotid injury in diabetic
      rats. Our results showed that N-glycosylation levels in both rat aortic
      endothelial cells (RAOECs) and rat vascular smooth muscle cells (VSMCs) decreased
      gradually following glucose treatment in a concentration dependant manner.
      Furthermore, co-immunoprecipitation (Co-IP) analyses indicated that SERP1 could
      interact with GLP-1R in RAOECs and VSMCs. Moreover, SERP1 enhanced GLP-1R N
      glycosylation and increased the production of phosphorylated endothelial nitric
      oxide synthase (eNOS) as well as proliferation of RAOECs. SERP1 also increased
      phosphorylated adenosine monophosphate activated protein kinase (AMPK) and
      decreased the migration of VSMCs. Importantly, intima media thickness (IMT) and
      neointimal hyperplasia were alleviated in the carotid artery of diabetic rats
      injected with SERP1 following balloon injury. We also found an increase in re
      endothelialization and a decrease in VSMC proliferation in the carotid artery of
      diabetic rats injected with SERP1. In summary, the remarkable effects of SERP1 on
      reducing restenosis following vascular injury may contribute to future
      advancements in the treatment of diabetic vascular complications.

PMID- 29656186
TI  - DCLK1 plays an important role in colorectal cancer tumorgenesis through the
      regulation of miR-200c.
AB  - Doublecortin-like kinase 1 (DCLK1) is a protein kinase that is known as a
      specific cancer stem cell (CSC) marker in colorectal cancer (CRC). Deregulation
      of DCLK1 expression has been reported in various cancers. We measured the protein
      expression of DCLK1 in 38 CRC and normal colon samples by immunohistochemistry
      (IHC). HCT-116 and SW-48 cells were transfected with DCLK1 siRNA and analyzed for
      expression of DCLK1 and miR-200c. The effects of DCLK1 knockdown on cell
      migration, invasion, sphere-forming, and apoptosis were explored. It was found
      that DCLK1 protein expression levels were significantly higher in CRC tissue than
      in normal colon specimens. Silencing of DCLK1 significantly inhibited cell
      migration, invasion, and sphere-forming potential; it also induced apoptosis as
      well as increased expression of miR-200c. Furthermore, silencing of miR-200c
      significantly up-regulated DCLK1 expression. Overall, our data demonstrated that
      DCLK1 plays an important role in cancer progression and is involved in the
      regulation of miR-200c expression.

PMID- 29656187
TI  - SIRT1 expression regulates the transformation of resistant esophageal cancer
      cells via the epithelial-mesenchymal transition.
AB  - Sirtuin1 (SIRT1) belongs to the mammalian sirtuin family and plays an important
      role in deacetylating histones and non-histones. SIRT1 is associated with tumor
      metastasis in several tumors. However, the effect of SIRT1 on the mechanism of
      metastasis in resistant esophageal cancer remains unclear. In this study, we
      demonstrated that increased migration and invasion in drug-resistant esophageal
      cancer cells (EC109/PTX, TE-1/PTX). Our experiments revealed that the selective
      SIRT1 inhibitor (EX527) significantly suppressed cells migrate and inhibited the
      occurrence of the epithelial-mesenchymal transition (EMT), thereby altering the
      invasiveness and metastatic potential of the esophageal cancer cell lines. In
      addition, we observed that the inhibition of SIRT1 could alter the expression of
      snail. In conclusion, these results indicate that SIRT1 may promote the
      transformation of tumor cells by inducing the EMT and may serve as a potential
      molecular target for the treatment of resistant esophageal cancer.

PMID- 29656188
TI  - Inhibition of the dopamine transporter as an animal model of bipolar disorder
      mania: Locomotor response, neuroimmunological profile and pharmacological
      modulation.
AB  - Inhibition of dopamine transporter (DAT) by GBR12909 has been proposed as a
      pharmacological model of mania related to bipolar disorder (BD). Here we tested
      the hypothesis that GBR12909 injection impairs habituation and induces
      hyperlocomotion in mice, along with changes in cytokines and neurotrophic factors
      levels, as observed in BD patients. We also tested if lithium carbonate, sodium
      valproate and aripiprazole prevent GBR12909-induced locomotion. Male Swiss mice
      received GBR12909 (15 mg/kg) injections and locomotor responses were quantified
      in an open field. Cytokines and neurotrophic factors levels were assessed in the
      prefrontal cortex, striatum and hippocampus 30 min and 24 h after injections. Pre
      treatments with lithium, valproate or aripiprazole were performed with single and
      repeated injection protocols. GBR12909 prevented motoric habituation and
      increased basal locomotion in habituated mice in the open field. This compound
      also induced changes in IL-2 and BDNF levels in prefrontal cortex; IL-2, IL-4 and
      IL-10 in striatum; and IL-10, IL-4, IFN-gamma and NGF in hippocampus. GBR12909
      induced hyperlocomotion was attenuated by lithium (12.5-100 mg/kg), but not
      valproate (75-300 mg/kg), and prevented by aripiprazole (0.1-10 mg/kg). Repeated
      injections of these drugs (twice a day for 3 days), however, failed to inhibit
      hyperlocomotion. The main limitations of the protocols in this study are the
      analysis of locomotion as the only behavioral parameter, changes in immune
      factors that may overlap with other psychiatric disorders and the lack chronic
      drug injections. Despite of these limitations, this study adds to previous
      literature suggesting DAT inhibition as a potential animal model of mania related
      to BD.

PMID- 29656189
TI  - Quantitative electroencephalography as a marker of cognitive fluctuations in
      dementia with Lewy bodies and an aid to differential diagnosis.
AB  - OBJECTIVE: We investigated for quantitative EEG (QEEG) differences between
      Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and Parkinson's disease
      dementia (PDD) patients and healthy controls, and for QEEG signatures of
      cognitive fluctuations (CFs) in DLB. METHODS: We analysed eyes-closed, resting
      state EEGs from 18 AD, 17 DLB and 17 PDD patients with mild dementia, and 21 age
      matched controls. Measures included spectral power, dominant frequency (DF),
      frequency prevalence (FP), and temporal DF variability (DFV), within defined EEG
      frequency bands and cortical regions. RESULTS: DLB and PDD patients showed a
      leftward shift in the power spectrum and DF. AD patients showed greater DFV
      compared to the other groups. In DLB patients only, greater DFV and EEG slowing
      were correlated with CFs, measured by the clinician assessment of fluctuations
      (CAF) scale. The diagnostic accuracy of the QEEG measures was 94% (90.4-97.9%),
      with 92.26% (80.4-100%) sensitivity and 83.3% (73.6-93%) specificity. CONCLUSION:
      Although greater DFV was only shown in the AD group, within the DLB group a
      positive DFV - CF correlation was found. QEEG measures could classify DLB and AD
      patients with high sensitivity and specificity. SIGNIFICANCE: The findings add to
      an expanding literature suggesting that EEG is a viable diagnostic and symptom
      biomarker in dementia, particularly DLB.

PMID- 29656190
TI  - Effect of titanium dioxide nanoparticles on the bioavailability and neurotoxicity
      of cypermethrin in zebrafish larvae.
AB  - In aquatic environment, the presence of nanoparticles (NPs) has been reported to
      modify the bioavailability and toxicity of the organic toxicants. Nevertheless,
      the combined toxicity of NPs and the pesticides that were used world-widely still
      remains unclear. Cypermethrin (CYP), a synthetic pyrethroid insecticide, is
      commonly used for controlling agricultural and indoor pests. Therefore, the
      effects of titanium dioxide NPs (nTiO2) on CYP bioconcentration and its effects
      on the neuronal development in zebrafish were investigated in our study.
      Zebrafish embryos (2- hour-post-fertilization, hpf) were exposed to CYP (0, 0.4,
      2 and 10 MUg/L) alone or co-exposed with nTiO2 (1 mg/L) until 120-hpf. nTiO2 is
      taken up by zebrafish larvae and also it can adsorb CYP. The zebrafish body
      burdens of CYP was observed and CYP uptake was increased by nTiO2, indicating
      that the nTiO2 could accelerate the bioaccumulation of CYP in larvae. Co-exposure
      of nTiO2 and CYP induced the generation of reactive oxygen species. Exposure to
      CYP alone significantly decreased the mRNA expression of genes, including glial
      fibrillary acidic protein (gfap), alpha1-tubulin, myelin basic protein (mbp) and
      growth associated protein (gap-43). Besides, reductions of serotonin, dopamine
      and GABA concentrations were observed in zebrafish and the larval locomotion was
      significantly decreased in response to the lower level of the neurotransmitters.
      Moreover, co-exposure of nTiO2 and CYP caused further significantly decreased in
      the locomotion activity, and enhanced the down-regulation of the mRNA expression
      of specific genes and the neurotransmitters levels. The results demonstrated that
      nTiO2 increased CYP accumulation and enhanced CYP-induced developmental
      neurotoxicity in zebrafish.

PMID- 29656191
TI  - Instability diagnosis and syntrophic acetate oxidation during thermophilic
      digestion of vegetable waste.
AB  - Effective process monitoring and instability diagnosis are important for stable
      anaerobic digestion (AD) of vegetable waste (VW). In order to evaluate the
      performance of thermophilic digestion of VW, to make early diagnosis for
      instability after organic overload, and to reveal the dynamics of microbial
      community under different running states, thermophilic AD of VW was carried out
      under improved organic loading rates (OLR) of 0.5-2.5 g volatile solid (VS)/(L ?
      d) in this study. Gaseous parameters including volumetric methane production rate
      (VMPR), CH4, CO2, and H2 concentrations, and liquid parameters including pH,
      oxidation-reduction potential, volatile fatty acid (VFA), and total alkalinity
      (TA), bicarbonate alkalinity (BA), intermediate alkalinity (IA), and ammonia,
      were monitored. The coupling parameters, such as the CH4/CO2, VFA/BA, and BA/TA
      ratios were also used to evaluate stability. The dynamics of syntrophic acetate
      oxidizing bacteria (SAOB), acetoclastic methanogens (AM), and hydrogenotrophic
      methanogens (HM) were analyzed by high-throughput sequencing. The main
      methanogenic bacteria were HM (Methanothermobacter) during the start-up period of
      OLR 0.5 gVS/(L ? d), while they were AM (Methanosarcina) during the stable period
      of OLR of 1.0 gVS/(L ? d). The VMPR of stable period was about 0.29 L/(L . d)
      with total VFA concentration below 100 mg/L, CH4/CO2 > 1.3, and BA/TA>0.9. The
      first instability due to the accumulation of VFA and self-recovery due to
      syntrophic acetate oxidation occurred at an OLR of 1.5 gVS/(L ? d). The
      syntrophic acetate-oxidizing bacteria probably belong to genus S1 (family
      Thermotogaceae). The digestion failed at an OLR of 2.0 g VS/(L . d). H2 was only
      detected during collapsed period instead of instable period. The total ammonia
      nitrogen loss and bicarbonate alkalinity (BA) reduction were the primary causes
      for the instability of AD of VW without effluent recirculation. Compared with
      single parameters, the CH4/CO2 and BA/total alkalinity (TA) ratios are
      recommended as early warning indicators for engineering applications of
      thermophilic AD of VW.

PMID- 29656192
TI  - In vitro bioanalysis of drinking water from source to tap.
AB  - The presence of chemical pollutants in sources of drinking water is a key
      environmental problem threatening public health. Efficient removal of pollutants
      in drinking water treatment plants (DWTPs) is needed as well as methods for
      assessment of the total impact of all present chemicals on water quality. In the
      present study we have analyzed the bioactivity of water samples from source to
      tap, including effects of various water treatments in a DWTP, using a battery of
      cell-based bioassays, covering health-relevant endpoints. Reporter gene assays
      were used to analyze receptor activity of the aryl hydrocarbon receptor (AhR),
      estrogen receptor (ER), androgen receptor (AR), peroxisome proliferator-activated
      receptor alpha (PPARalpha) and induction of oxidative stress by the nuclear
      factor erythroid 2-related factor 2 (Nrf2). DNA damage was determined by Comet
      assay. Grab water samples were concentrated by HLB or ENV solid phase extraction
      and the water samples assayed at a relative enrichment factor of 50. The
      enrichment procedure did not induce any bioactivity. No bioactivity was detected
      in Milli-Q water or drinking water control samples. Induction of AhR, ER and Nrf2
      activities was revealed in source to tap water samples. No cytotoxicity,
      PPARalpha or AR antagonist activity, or DNA damage were observed in any of the
      water samples. A low AR agonist activity was detected in a few samples of surface
      water, but not in the samples from the DWTP. The treatment steps at the DWTP,
      coagulation, granulated activated carbon filtration, UV disinfection and NH2Cl
      dosing had little or no effect on the AhR, Nrf2 and ER bioactivity. However,
      nanofiltration and passage through the distribution network drastically decreased
      AhR activity, while the effect on Nrf2 activity was more modest and no apparent
      effect was observed on ER activity. The present results suggest that bioassays
      are useful tools for evaluation of the efficiency of different treatment steps in
      DWTPs in reducing toxic activities. Bioassays of AhR and Nrf2 are useful for
      screening of effects of a broad range of chemicals in drinking water and ER
      activity can be monitored with a high sensitivity.

PMID- 29656193
TI  - Trade-offs in ecosystem impacts from nanomaterial versus organic chemical
      ultraviolet filters in sunscreens.
AB  - Both nanoparticulate (nZnO and nTiO2) and organic chemical ultraviolet (UV)
      filters are active ingredients in sunscreen and protect against skin cancer, but
      limited research exists on the environmental effects of sunscreen release into
      aquatic systems. To examine the trade-offs of incorporating nanoparticles (NPs)
      into sunscreens over the past two decades, we targeted endpoints sensitive to the
      potential risks of different UV filters: solar reactive oxygen production in
      water and disruption of zebrafish embryo development. First, we developed
      methodology to extract nanoparticles from sunscreens with organic solvents.
      Zebrafish embryos exposed to parts-per-million NPs used in sunscreens displayed
      limited toxicological effects; nZnO particles appeared to be slightly more toxic
      than nTiO2 at the highest concentrations. In contrast, seven organic UV filters
      did not affect zebrafish embryogenesis at or near aqueous solubility. Second, to
      simulate potent photo-initiated reactions upon release into water, we examined
      methylene blue (MB) degradation under UV light. nTiO2 from sunscreen caused 10
      times faster MB loss than nZnO and approached the photocatalytic degradation rate
      of a commercial nTiO2 photocatalysts (P25). Organic UV filters did not cause
      measurable MB degradation. Finally, we estimated that between 1 and 10 ppm of
      sunscreen NPs in surface waters could produce similar steady state hydroxyl
      radical concentrations as naturally occurring fluvic acids under sunlight
      irradiation. Incorporation of NPs into sunscreen may increase environmental
      concentrations of reactive oxygen, albeit to a limited extent, which can
      influence transformation of dissolved substances and potentially affect ecosystem
      processes.

PMID- 29656194
TI  - Multiple dynamic Al-based floc layers on ultrafiltration membrane surfaces for
      humic acid and reservoir water fouling reduction.
AB  - The integration of adsorbents with ultrafiltration (UF) membranes is a promising
      method for alleviating membrane fouling and reducing land use. However,
      adsorbents typically are only injected into the membrane tank once, resulting in
      a single dynamic protection layer and low removal efficiency over long-term
      operation. In addition, the granular adsorbents used can cause membrane surface
      damage. To overcome these disadvantages, we injected inexpensive and loose
      aluminum (Al)-based flocs directly into a membrane tank with bottom aeration in
      the presence of humic acid (HA) or raw water taken from the Miyun Reservoir
      (Beijing, China). Results showed that the flocs were well suspended in the
      membrane tank, and multiple dynamic floc protection layers were formed (sandwich
      like) on the membrane surface with multiple batch injections. Higher frequency
      floc injections resulted in better floc utilization efficiency and less severe
      membrane fouling. With continuous injection, acid solutions demonstrated better
      performance in removing HA molecules, especially those with small molecular
      weight, and in alleviating membrane fouling compared with the use of high
      aeration rate or polyacrylamide injection. This was attributed to the small
      particle size, large specific surface area, and high zeta potential of the flocs.
      Additionally, excellent UF membrane performance was exhibited by reservoir water
      with continuous injection and acid solution. Based on the outstanding UF membrane
      performance, this innovative integrated filtration with loose Al-based flocs has
      great application potential for water treatment.

PMID- 29656195
TI  - Direct analysis of deodorants for determination of metals by inductively coupled
      plasma optical emission spectrometry.
AB  - A fast and simple dilute-and-shoot procedure for determination of Al, As, Ba, Cd,
      Cu, Fe, Mg, Mn, Ni, Pb, Sc, Ti, V, Zn and Zr in deodorants by inductively coupled
      plasma optical emission spectrometry (ICP OES) was developed. Sample preparation
      was carried out by diluting 1 mL of deodorant sample in 1% (v v-1) HNO3. The
      accuracy of the analytical procedure was evaluated using addition and recovery
      experiments, and recoveries ranged from 80 to 119%. The limits of detection
      varied from 0.001 to 0.76 mg kg-1. Nine deodorants samples of different brands
      were analyzed. The maximum concentrations found (mg kg-1) were: Fe (1.0), Mn
      (0.1), Ti (1.02), V (0.33), Zn (255.2) and Zr (0.5); for Al and Mg, determined
      concentrations varied from 0.01 to 7.0% and from 0.005 to 1.44 mg kg-1,
      respectively, showing wide variation depending on the sample type. The developed
      procedure was adequate for determining these analytes in routine analysis
      presenting high sample throughput and demonstrated the feasibility of direct
      analysis measurements after simple dilution step.

PMID- 29656196
TI  - A fast and robust hydrophilic interaction liquid chromatography tandem mass
      spectrometry method for determining methylpentose, hexose, hexosamine and hexonic
      acid in pneumococcal polysaccharide vaccine hydrolysates.
AB  - The conventional UV/Vis spectroscopy methods recommended by the European
      Pharmacopoeia (EP) for determining hexosamine, hexonic acid and methylpentose in
      pneumococcal polysaccharide vaccine (PPSV) hydrolates are time-consuming due to
      derivatization process (typically, an analysis cycle is more than 4 h) and
      improvements of selectivity and precision of the methods are in demand. In this
      study, a new approach based on hydrophilic interaction liquid chromatography and
      triple quadrupole mass spectrometry (HILIC-MS/MS) was optimized to overcome the
      drawbacks of the EP methods for simultaneous determination of methylpentose,
      hexose, hexosamine and hexonic acid in PPSV hydrolysates. The chromatographic, MS
      and sample hydrolysis conditions were systematically investigated. A zwitterionic
      column, Click Cys, using a gradient elution with a mobile phase of 10 mM ammonium
      formate (pH 4.3) in acetonitrile from 72% to 21% in 6 min was applied for
      separating the targets, which exhibited low column bleeding, easy equilibration
      and long-term stability. The HILIC-MS/MS method showed a high sensitivity (LOD =
      0.98 MUg L-1 for hexonic acid), a good repeatability (RSD of peak area less than
      1.669%), accuracy (92.9%-104.2%), recovery (97.6%-99.3%) and a wide linear range.
      The RSD of retention time obtained from more than 3000 injections in three months
      was less than 1.64%. The new method was compared with the EP method for
      determining hexosamine in 23 serotypes of PPSV hydrolysates. The results
      indicated that the new HILIC-MS/MS method was highly selective, accurate, stable
      and extremely fast due to without need of derivatization, as compared to the
      conventional EP methods.

PMID- 29656197
TI  - Design and synthesis of BPR1K653 derivatives targeting the back pocket of Aurora
      kinases for selective isoform inhibition.
AB  - Twenty five novel chemical analogs of the previously reported Aurora kinase
      inhibitor BPR1K653 (1-(4-(2-((5-chloro-6-phenylfuro[2,3-d]pyrimidin-4
      yl)amino)ethyl)phenyl)-3-(2-((dimethylamino)methyl)phenyl)urea) have been
      designed, synthesized, and evaluated by Aurora-A and Aurora-B enzymatic kinase
      activity assays. Similar to BPR1K653, analogs 3b-3h bear alkyl or tertiary amino
      group at the ortho position of the phenylurea, and showed equal or better
      inhibition activity for Aurora-B over Aurora-A. Conversely, preferential Aurora-A
      inhibition activity was observed when the same functional group was moved to the
      meta position of the phenylurea. Compounds 3m and 3n, both of which harbor a
      tertiary amino group at the meta position of the phenylurea, showed 10-16 fold
      inhibition selectivity for Aurora-A over Aurora-B. The in vitro kinase inhibition
      results were verified by Western blot analysis, and indicated that compounds 3m
      and 3n were more than 75-fold superior in inhibiting T-loop autophosphorylation
      of Aurora-A (Thr288), compared to Aurora-B (Thr232) in HCT116 colon carcinoma
      cells. The computational docking analysis suggested that the tertiary amine at
      the meta position of the phenylurea formed a more stable interaction with
      residues in the back pocket of Aurora-A than in Aurora-B, a possible explanation
      for the observed discrepancy in the selectivity. These results support an
      alternative small molecule design strategy targeting the back pocket of Aurora
      kinases for selective isoform inhibition.

PMID- 29656198
TI  - Synthesis and biological evaluation of 2,5-disubstituted furan derivatives as P
      glycoprotein inhibitors for Doxorubicin resistance in MCF-7/ADR cell.
AB  - Multidrug resistance (MDR) is a tendency in which cells become resistant to
      structurally and mechanistically unrelated drugs, which is mediated by P
      glycoprotein (P-gp). It is one of the noteworthy problems in cancer therapy. As
      one of the most important drugs in cancer therapy, doxorubicin has not good
      effectiveness if used independently. So targeting the P-gp protein is one of the
      key points to solve the MDR. Three series of furan derivatives containing
      tetrahydroquinoline or tetrahydroisoquinoline were designed and synthesized as P
      gp inhibitors in this paper. Compound 5m containing 6,7-dimethoxy-1,2,3,4
      tetrahydroisoquinoline possessed good potency against P-gp (EC50 = 0.89 +/- 0.11
      MUM). The preliminary structure-activity relationship and docking studies
      demonstrated that compound 5m would be great promise as a lead compound for
      further study. Most worthy of mention is drug combination of doxorubicin and 5m
      displayed antiproliferative effect of about 97.8%. This study provides
      highlighted P-gp inhibitor for withstanding malignant tumor cell with multidrug
      resistance especially doxorubicin resistance setting the basis for further
      studies.

PMID- 29656199
TI  - Investigating isoindoline, tetrahydroisoquinoline, and tetrahydrobenzazepine
      scaffolds for their sigma receptor binding properties.
AB  - Substituted norbenzomorphans are known to display high affinity and selectivity
      for the two sigma receptor (sigmaR) subtypes. In order to study the effects of
      simplifying the structures of these compounds, a scaffold hopping strategy was
      used to design several novel sets of substituted isoindolines,
      tetrahydroisoquinolines and tetrahydro-2-benzazepines. The binding affinities of
      these new compounds for the sigma 1 (sigma1R) and sigma 2 (sigma2R) receptors
      were determined, and some analogs were identified that exhibit high affinity (Ki
      <= 25 nM) and significant selectivity (>10-fold) for sigma1R or sigma2R. The
      preferred binding modes of selected compounds for the sigma1R are predicted by
      modeling studies, and the nature of substituents on the aromatic ring and the
      nitrogen atom of the bicyclic skeleton appears to affect the preferred binding
      orientation of sigma1R-preferring ligands.

PMID- 29656200
TI  - Photoinduced anticancer activity studies of iridium(III) complexes targeting
      mitochondria and tubules.
AB  - Three new iridium (III) complexes [Ir (ppy)2 (ipbc)](PF6) (1), [Ir (bzq)2
      (ipbc)](PF6) (2) and [Ir (piq)2 (ipbc)](PF6) (3) were designed and synthesized.
      All the complexes were tested for anticancer activity using 3-(4,5
      dimethylthiazole)-2,5-diphenyltetraazolium bromide (MTT) method. The complexes
      show no cytotoxic activity toward cancer BEL-7402, SGC-7901, Eca-109, A549, HeLa
      and HepG2 cells. However, upon irradiation with white light, the complexes
      display high cytotoxicity against BEL-7402 cells with an IC50 value of 5.5 +/-
      0.8, 7.3 +/- 1.3 and 11.5 +/- 1.6 MUM for 1, 2 and 3, respectively. AO/EB
      staining and comet assay show that the complexes can induce apoptosis in BEL-7402
      cells. The complexes can increase intracellular ROS and Ca2+ levels and cause a
      decrease in the mitochondrial membrane potential. Autophagic assays exhibit that
      the complexes can induce autophagy and regulate the expression of Beclin-1 and
      LC3 proteins. The cell cycle distribution in BEL-7402 cells was carried out by
      flow cytometry. The expression of Bcl-2 family proteins was studied by western
      blot. Additionally, the complexes can release cytochrome c and inhibit the
      polymerization of alpha-tubulin. Our study reveals that the complexes inhibit the
      cell growth in BEL-7402 cells through an ROS-mediated mitochondria dysfunction
      and targeting tubules pathways. These complexes are a promising new entity for
      the development of multi-target anticancer drugs.

PMID- 29656201
TI  - Anti-leishmanial click modifiable thiosemicarbazones: Design, synthesis,
      biological evaluation and in silico studies.
AB  - Leishmaniasis is a devastating tropical disease with limited therapeutic options.
      Depending on recently reported active anti-leishmanial compounds, we designed and
      synthesized a series of click modifiable 1,2,3-triazole and thiosemicarbazone
      hybrids. Most of the synthesized compounds showed comparable to superior activity
      to a well-established anti-leishmanial drug miltefosine. Compounds 2 and 10a
      showed nanomolar IC50s against promastigotes of L. major (227.4 nM and 140.3 nM
      respectively, vs 7.8 MUM for miltefosine). Their antiamastigote IC50s were 1.4
      MUM and 1 MUM respectively, which are 6 and 8 times the activity of miltefosine
      (IC50 8.09 MUM). Folic and folinic acids reversed the anti-leishmanial effects of
      compounds 2 and 10a and hence we anticipate they act via an anti-folate
      mechanism. They exhibited better safety profiles than that of miltefosine on VERO
      cell lines. Also they were relatively safe on experimental mice when administered
      via oral and parenteral routes. Docking experiments on PTR1 identified
      preferential binding interactions and docking scores. Finally, drug-likeness and
      ligand efficiency were assessed indicating that both 2 and 10a are promising hits
      and/or leads as anti-leishmanial chemotherapeutic agents.

PMID- 29656202
TI  - Syntheses and anti-pancreatic cancer activities of rakicidin A analogues.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignant tumor
      and resistant to most therapies. Pancreatic cancer stem cells (PCSCs) had
      critical role in regulating PDAC progression, metastasis, and drug resistance.
      Therefore, targeting PCSCs is considered to be a promising strategy for treatment
      of PDAC. However, there is no effective drug that can selectively ablate PCSCs. A
      series of twenty rakicidin A analogues were synthesized via a combinatorial
      strategy and evaluated for their anti-PDAC activities, and the structure-activity
      relationship was also discussed. Compound 32g was prepared in 14 linear steps
      with 5.05% overall yield, which is much more efficient than our previously
      reported total synthesis of rakicidin A (19 linear steps with 0.19% yield). In a
      highly metastatic pancreatic cancer cell line ASPC-1, compound 32g showed about 4
      times higher potency (IC50 = 0.022 MUM) than rakicidin A (IC50 = 0.082 MUM) at
      hypoxia condition, and 12 folds of hypoxia selectivity (IC50 = 0.27 MUM at
      nomoxia condition). In contrast, the activity of adriamycin in the same hypoxic
      condition decreased. The percentage of PCSCs (with CD24+CD44+ESA+ biomarker),
      activity of ALDH, and the number of tumorspheres in PANC-1 cells were greatly
      reduced after treatment of 32g. More importantly, the tumor-initiating frequency
      was reduced by 19 folds after the treatment of 32g, which is better than that of
      rakicidin A (reduction of 4.7 folds).

PMID- 29656203
TI  - An overview of quinazolines: Pharmacological significance and recent
      developments.
AB  - Most of the drugs and pharmacologically relevant molecules possess heterocyclic
      ring structures and presence of hetero atoms or groupings divulges privileged
      specificities in their pharmacological targets. Especially the heterocyclic
      systems, quinazoline is a biologically imperative scaffold known to be linked
      with several pharmacological activities. Some of the protuberant pharmacological
      responses attributed to this system are analgesic, anti-inflammatory, anti
      convulsant, sedative-hypnotic, anti-histaminic, anti-hypertensive, anti-cancer,
      anti-microbial, anti-tubercular and anti-viral activities. This multiplicity in
      the pharmacological response contours of quinazoline has attracted the
      consideration of medicinal chemists to explore this system to its multiple
      potential against numerous activities. Several of these synthetic and
      pharmacological investigations have been successively studied for structure
      activity relationship (SAR) to correlate the particular structural features for
      their pharmacological target. The emerging understanding of quinazoline
      derivatives on their pharmacological target offer opportunities for novel
      therapeutics. This review principally emphases on the medicinal chemistry aspects
      including drug design, structure-activity relationships (SARs), and mechanism of
      actions of quinazoline derivatives. This review gives detailed attention on in
      vitro and in vivo pharmacological activities of quinazoline and its analogs in
      the perspective of drug discovery and its development.

PMID- 29656204
TI  - Surface hydroxylation regulates cellular osteogeneses on TiO2 and Ta2O5 nanorod
      films.
AB  - Titanium and tantalum have been widely used for orthopedic and dental implant
      applications. However, how their inherent surface features regulate cellular
      osteogeneses still remains elusive. In this study, we engineered two distinct
      TiO2 and Ta2O5 nanorod films as the two model oxidized surfaces to investigate
      their intrinsic osteogenic behaviors. The results indicated that the distinctive
      gradient on zeta potential against pH, corresponding to the deprotonation rate,
      but not the hydroxyl amount or hydroxylation polarity played a critical role on
      the cellular osteogenic performance. TiO2 nanorod film with a higher
      deprotonation rate significantly upregulated the expression of osteogeneses
      related gene and protein, comparing to that of Ta2O5 nanorod film. These results
      might be attributed to that surface with higher deprotonation rateprovided more
      Bronsted acid-base surface sites to react with protein residues, leading to a
      mild change in conformation of the absorbed proteins, and subsequently
      facilitating to trigger the integrin-focal adhesion cytoskeleton actin
      transduction pathway. This study, therefore, provides a new insight into the
      understanding the role of material surface hydroxylation on cellular osteogenic
      responses.

PMID- 29656205
TI  - A nano-bio interfacial protein corona on silica nanoparticle.
AB  - Nano-bio interaction takes the crucial role in bio-application of nanoparticles.
      The systematic mapping of interfacial proteins remains the big challenge as low
      level of proteins within interface regions and lack of appropriate technology.
      Here, a facile proteomic strategy was developed to characterize the interfacial
      protein corona (noted as IPC) that has strong interactions with silica
      nanoparticle, via the combination of the vigorous elution with high concentration
      sodium dodecyl sulfate (SDS) and the pre-isolation of sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE). The trace level IPCs for silica
      nanoparticle were thus qualitatively and quantitatively identified.
      Bioinformatics analyses revealed the intrinsic compositions, relevance and
      potential regularity addressing the strong interactions between IPC and
      nanoparticle. This strategy in determining IPCs is opening an avenue to give a
      deep insight to understand the interaction between proteins and not only
      nanoparticles but also other bulk materials.

PMID- 29656206
TI  - Enhancing first-time parents' self-efficacy: A systematic review and meta
      analysis of universal parent education interventions' efficacy.
AB  - BACKGROUND: Poor adjustment during early parenthood often leads to low feelings
      of parental self-efficacy, which influences parents' behaviours towards their
      infants. The long-term consequences on infant development warrant the need for
      more attention on the efficacy of universal parent education interventions to
      empower parents and enhance their self-efficacy. OBJECTIVES: To synthesise
      available evidence and explore the efficacy of universal parent education
      interventions on the parental self-efficacy of first-time parents. DESIGN: A
      systematic review and meta-analysis of randomised controlled trials. DATA
      SOURCES: A literature search of 10 databases was conducted to identify randomised
      controlled trials from each database's point of inception to November 2016.
      METHODS: Based on the inclusion criteria, 24,062 articles were screened for their
      titles and abstracts. Two hundred and eighty articles were identified for full
      text screening. Risks of bias posed by the selected articles were assessed using
      Cochrane's Risk of Bias instrument. Meta-analyses were conducted using RevMan
      5.3. The overall intervention effect was evaluated using z tests at p < 0.05,
      while I2 and Cochran Q tests were used to measure heterogeneity. RESULTS: Ten
      randomised controlled trials were selected; eight trials were combined in meta
      analyses and two trials were synthesised narratively. A meta-analysis revealed
      that universal parent education interventions significantly enhanced parental
      self-efficacy (p < 0.001) among first-time parents and these effects were also
      maintained over time (p < 0.001). The extent of improvement in parental self
      efficacy was affected by the duration of the interventions. CONCLUSION: This
      review provides sufficient evidence to support the use of universal interventions
      to enhance new parents' self-efficacy. While intervention effects were sustained
      at the two-month follow-up, further research using randomised controlled trials
      and longitudinal studies are needed to determine long-term effects. The findings
      serve as an impetus for hospitals and healthcare professionals to integrate
      universal interventions in perinatal care to guide first-time parents' transition
      into parenthood.

PMID- 29656207
TI  - Dihydromyricetin relieves rheumatoid arthritis symptoms and suppresses expression
      of pro-inflammatory cytokines via the activation of Nrf2 pathway in rheumatoid
      arthritis model.
AB  - Rheumatoid arthritis (RA) is a systemic inflammatory and autoimmune disease. In
      this research, we estimated the protective effects of Dihydromyricetin (DMY) on
      RA induced by Complete Freund's Adjuvant (CFA). We found that DMY effectively
      relieved rheumatoid arthritis symptoms, such as body weight change, paw swelling
      and rheumatoid arthritis scores. In addition, we also observed that DMY
      significantly lowered the immune organ indexes (including thymus and spleen) and
      exhibited the anti-inflammatory effect in CFA-induced rheumatoid arthritis. The
      results demonstrated that the increased expression levels of interleukin-1beta
      (IL-1beta), interleukin-6(IL-6), tumor necrosis factor-alpha (TNF-alpha) were
      significantly inhibited by DMY. Furthermore, the key inflammatory mediator,
      cyclooxygenase-2 (COX-2) was markedly lowered after treatment with DMY. A
      mechanistic study indicated that DMY could up-regulate the down-regulation levels
      of the mRNA and protein of Nrf2, HO-1 and NQO1. Moreover, the Nrf2 activation of
      DMY was abolished by Nrf2 inhibitor brusatol. Thus, DMY inhibits the expressions
      of pro-inflammatory cytokines via activating Nrf2 pathway in RA model, which
      suggests that DMY has potential for further investigation as a candidate anti
      arthritic agent in future.

PMID- 29656208
TI  - Akt, mTOR and NF-kappaB pathway activation in Treponema pallidum stimulates M1
      macrophages.
AB  - The polarization of macrophages and the molecular mechanism involved during the
      early process of syphilis infection remain unknown. This study was conducted to
      explore the influence of Treponema pallidum (T. pallidum) treatment on macrophage
      polarization and the Akt-mTOR-NFkappaB signaling pathway mechanism involved in
      this process. M0 macrophages derived from the phorbol-12-myristate-13-acetate
      induced human acute monocytic leukemia cell line THP-1 were cultured with T.
      pallidum. T. pallidum induced inflammatory cytokine (IL-1beta and TNF-alpha)
      expression in a dose- and time-dependent manner. However IL-10 cytokine
      expression decreased at the mRNA and protein levels. Additionally, the expression
      of the M1 surface marker iNOS was up-regulated with incubation time, and the
      expression of the M2 surface marker CD206 was low (vs. PBS treated macrophages, P
      < 0.001) and did not fluctuate over 12 h. Further studies revealed that Akt-mTOR
      NFkappaB pathway proteins, including p-Akt, p-mTOR, p-S6, p-p65, and p
      IkappaBalpha, were significantly higher in the T. pallidum-treated macrophages
      than in the PBS-treated macrophages (P < 0.05). In addition, inflammatory
      cytokine expression was suppressed in T. pallidum-induced M1 macrophages
      pretreated with LY294002 (an Akt-specific inhibitor) or PDTC (an NF-kappaB
      inhibitor), while inflammatory cytokine levels increased in T. pallidum-induced
      M1 macrophages pretreated with rapamycin (an mTOR inhibitor). These findings
      revealed that T. pallidum promotes the macrophage transition to pro-inflammatory
      M1 macrophages in vitro. The present study also provides evidence that Akt, mTOR
      and NF-kappaB pathway activation in T. pallidum stimulates M1 macrophages. This
      study provides novel insights into the innate immune response to T. pallidum
      infection.

PMID- 29656209
TI  - Phosphorylation of low density lipoprotein receptor-related protein 6 is involved
      in receptor for advanced glycation end product-mediated beta-catenin
      stabilization in a toluene diisocyanate-induced asthma model.
AB  - BACKGROUND: We have previously demonstrated that the receptor for advanced
      glycation end products (RAGE)/beta-catenin axis plays a vital role in regulating
      airway inflammation and airway remodeling in a toluene diisocyanate (TDI)-induced
      murine asthma model. However, the exact mechanism of beta-catenin activation
      remains unclear. Given that phosphorylation of the low-density lipoprotein
      receptor-related protein 6 (Lrp6) is a key step in mediating beta-catenin
      stabilization in canonical wnt/beta-catenin signaling, we explored the possible
      relationship between RAGE and Lrp6 in regulating beta-catenin stabilization in
      TDI-induced asthma. METHODS: In this study, a TDI-induced murine asthma model was
      generated, and mice were treated with a specific inhibitor of RAGE. In vitro, the
      human bronchial epithelial cell line 16HBE was treated with TDI-human serum
      albumin (TDI-HSA). RAGE overexpression or knockdown cells were also constructed
      and assessed. RESULTS: The results showed that RAGE inhibition or RAGE knockdown
      decreased beta-catenin nuclear accumulation and the expression of relevant beta
      catenin targeted genes (VEGF, MMP9, TGF-beta1) in the TDI-induced murine asthma
      model and TDI-HSA-treated 16HBE cells, respectively. Silencing of RAGE reversed
      the TDI-induced increase in phospho-ERK1/2 (p-ERK) and phospho-Lrp6 (p-Lrp6) in
      16HBE cells. Pretreatment with the extracellular signal-regulated kinase (ERK)1/2
      inhibitor U0126 suppressed TDI-induced Lrp6 phosphorylation. Furthermore,
      knockdown of Lrp6 in 16HBE cells decreased beta-catenin nuclear translocation and
      the expression of VEGF, MMP9, and TGF-beta1. CONCLUSION: These data suggested
      that the RAGE/ERK axis modulates Lrp6 phosphorylation, contributing to beta
      catenin stabilization in a TDI-induced murine model.

PMID- 29656210
TI  - Micheliolide alleviates hepatic steatosis in db/db mice by inhibiting
      inflammation and promoting autophagy via PPAR-gamma-mediated NF-kB and AMPK/mTOR
      signaling.
AB  - The anti-inflammatory, immunomodulatory, and anticancer effects of micheliolide
      (MCL) isolated from Michelia champaca were previously reported, but its role and
      underlying mechanisms in relieving liver steatosis remain unclear. Herein, we
      investigated the effects of MCL on hepatic steatosis using a db/db mouse model
      and lipid mixture (LM)-induced AML12 and LO2 cells. The body and liver weights,
      food consumption, lipid content and liver aminotransferase levels in serum, the
      lipid content and inflammatory cytokine levels in liver tissue, and the extent of
      hepatic steatosis in db/db mice were increased compared with those in db/m mice,
      and these increases were reversed by MCL treatment. Similarly, MCL also
      attenuated the inflammatory responses and lipid accumulation in LM-treated AML12
      and L02 cells by upregulating PPAR-gamma and decreasing p-IkBalpha and p-NF
      kappaB/p65, thereby inhibiting the NF-kappaB pathway and reducing lipotoxicity.
      Furthermore, MCL administration increased LC3B, Atg7 and Beclin-1 expression and
      the LC3B-II/I ratio in db/db mouse livers and LM-treated AML12 and L02 cells, and
      these MCL-induced increases were mediated by the activation of PPAR-gamma and p
      AMPK and inhibition of p-mTOR and induce autophagy. These effects were blocked by
      PPAR-gamma and AMPK inhibitors. Our findings suggest that MCL ameliorates liver
      steatosis by upregulating PPAR-gamma expression, thereby inhibiting NF-kappaB
      mediated inflammation and activating AMPK/mTOR-dependent autophagy.

PMID- 29656211
TI  - Esculetin from Fraxinus rhynchophylla attenuates atopic skin inflammation by
      inhibiting the expression of inflammatory cytokines.
AB  - Atopic dermatitis (AD) is a common chronic inflammatory skin disorder afflicting
      from infancy to adults with itching, scratching, and lichenification. We aimed to
      investigate the effects of esculetin from Fraxinus rhynchophylla on atopic skin
      inflammation. For induction of atopic skin inflammation, we exposed the ears of
      female BALB/c mice to house dust mite (Dermatophagoides farinae extract, DFE) and
      2,4-dinitrochlorobenzene (DNCB) for 4 weeks. Oral administration of esculetin
      reduced the symptoms of DFE/DNCB-induced atopic skin inflammation, which were
      evaluated based on ear swelling and number of scratch bouts. The immunoglobulin
      (Ig) E, IgG2a, and histamine levels in serum were decreased and inflammatory cell
      infiltration in skin tissue was reduced by the esculetin. It suppressed
      production of Th1, Th2 and Th17-related cytokines such as tumor necrosis factor
      (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-4, IL-13, IL-31 and IL-17
      in the ear tissue. Furthermore, we investigated the effects of esculetin on
      activated keratinocytes, which are representative cells used for studying the
      pathogenesis of acute and chronic atopic skin inflammation. As results, esculetin
      suppressed gene expression of Th1, Th2 and Th17 cytokines and the activation of
      nuclear factor-kappaB and signal transducer and activator of transcription 1 in
      TNF-alpha/IFN-gamma-stimulated keratinocytes. Taken together, these results imply
      that esculetin attenuated atopic skin inflammation, suggesting that esculetin
      could be a potential therapeutic candidate for the treatment of AD.

PMID- 29656212
TI  - Myeloid related proteins are up-regulated in autoimmune thyroid diseases and
      activate toll-like receptor 4 and pro-inflammatory cytokines in vitro.
AB  - PURPOSE: Myeloid-related protein (MRP) family plays an important role in the
      promotion of cell proliferation and the production of inflammatory cytokines. We
      investigated the expression of MRP6, MRP8 and MRP14 in thyroid tissues, serum,
      and peripheral blood monocular cells (PBMCs) in patients with autoimmune thyroid
      diseases (AITD). METHOD: The expression of MRP6, MRP8, and MRP14 was investigated
      using immunohistochemical staining and quantitative real-time polymerase chain
      reaction in the thyroid glands of 7 patients with Graves' disease (GD), 8 with
      Hashimoto's thyroiditis (HT), and 7 healthy controls (HC). The serum levels of
      MRP8/MRP14 complex and MRP6 were investigated in 30 patients with GD, 36 with HT,
      and 30 with HC. The mRNA expression of MRP proteins in PBMCs was also explored.
      PBMCs from each group were incubated with MPRs and their effect on Toll-like
      receptor 4(TLR4) expression and their effect on the levels of the pro
      inflammatory cytokines in supernatant were analyzed upon incubating with TLR4 and
      signaling pathways inhibitors. RESULTS: Serum levels of MRP8/MRP14 and MRP6 were
      up-regulated in patients with AITD. In addition, mRNA expression of MRP proteins
      in PBMCs and the thyroid gland was markedly elevated in AITD patients. MRP6 and
      MPR8 promoted the secretion of TNF-alpha and IL-6 in cultured PBMCs, and this
      elevation was more pronounced in AITD patients; we also found that this up
      regulation was regulated by TLR4/phosphoinositide 3-kinase/nuclear factor-kappaB
      signaling pathway. CONCLUSION: The expression of MRP proteins was elevated in
      AITD patients. Therefore, an MRP-TLR4 dependent signaling may play an important
      role in the pathogenesis of AITD.

PMID- 29656213
TI  - Molecular characterization of voltage-gated potassium channel (Kv) and its
      importance in functional dynamics in bull spermatozoa.
AB  - Present study was undertaken to characterize the voltage gated potassium channel
      (Kv 1.1) in bull spermatozoa using sixty four ejaculates collected from four
      Hariana bulls. Functional characterization was undertaken using a selective
      blocker of Kv channel, 4-Aminopyridine (4-AP) while molecular presence of Kv on
      bull spermatozoa by immunoblotting and indirect immunofluorescence. Three sets of
      100 MUL diluted sperm samples namely-negative control (100 MUL of sperm dilution
      medium (SDM) containing 10 * 106 cells), vehicle control (99 MUL of SDM
      containing 10 * 106 cells, and DMSO- 1  MUL) and 4-AP treatment group (99 MUL of
      SDM containing 10 * 106 cells, and drug 1 MUL 4-AP) were used in the study.
      Immunoblotting identified a single band of 56 kDa corresponding to Kv1.1 in
      Hariana bull spermatozoa. Immunolocalization showed the positive immunoreactivity
      at head, middle piece and principal piece of the spermatozoa for Kv 1.1. Blocking
      of Kv using 4-AP resulted in significant (p < 0.05) reduction in sperm
      progressive motility, per cent capacitated spermatozoa (B-pattern) and acrosome
      reacted (AR-pattern) spermatozoa, while significant (P < 0.05) increase in per
      cent swollen spermatozoa. Blocking of Kv channels resulted in significantly (P <
      0.05) increased percentage of spermatozoa with lower mitochondrial transmembrane
      potential. Computer assisted semen analysis (CASA) of motion and kinematic
      parameters in 4-AP treated spermatozoa indicated reduction in sperm motion
      parameters like LIN, STR, VSL and VAP and higher ALH, VCL, and BCF indicating
      hyperactivity of spermatozoa. Based on our findings, it may be concluded that
      voltage-gated potassium channel (Kv) are present on bull spermatozoa and these
      are associated with functional dynamics of spermatozoa. However, based on our
      limited study, it is not possible to deduce that how these channels are
      associated with induction of hyperactivity. Therefore, further studies are
      warranted to unravel the mechanistic signaling pathways involved in Kv-mediated
      alterations in functional dynamics of spermatozoa.

PMID- 29656214
TI  - Study of virulence factor of Candida species in oral lesions and its association
      with potentially malignant and malignant lesions.
AB  - OBJECTIVE: The aim of this study was to explore the association between malignant
      and premalignant lesions and the virulence factor profile of Candida spp.
      recovered from different oral lesions. DESIGN: Candida spp. isolated from
      malignant lesions (squamous cell carcinoma, OC, n = 25), atypical lichen planus
      (AL, n = 11), chronic candidiasis (CC, n = 25), and asymptomatic carriers (WI, n
      = 15, control strains.) Isolates were identified in chromogenic medium, colony
      morphology and biochemical tests. The lipolytic and proteinase activity was
      determined on supplemented agar with olive oil and BSA, respectively. The biofilm
      formation with XTT reduction assay and cellular surface hydrophobicity (CSH) by
      water-hydrocarbon method were performed. RESULTS: All isolates recovered from
      oral lesions produced the four virulence factors studied with significantly
      higher levels than in WI isolates. Interestingly, lipolytic activity was absent
      in WI isolates. The proteolytic activity was similar in AL and OC isolates. OC
      isolates showed significantly higher CSH values than other clinical isolates. Non
      albicans species showed higher biofilm formation than C.albicans (P = 0.03.)
      There were no significant differences in virulence factors among species. A
      strong positive correlation was found between proteinase and lipase activity (r =
      0.90, P < 0.0001), and between hydrophobicity and biofilm (R = 0.81, P < 0.0001.)
      CONCLUSIONS: Our results indicate that OC Candida isolates exhibited a
      significant higher attributes of virulence than other lesions fungus isolates,
      providing evidence about the association between Candida pathogenicity and
      lesions severity.

PMID- 29656215
TI  - Inter-observer variance and the need for standardization in the morphological
      classification of myelodysplastic syndrome.
AB  - In this era of genome medicine, the sub-classification of myeloid neoplasms,
      including myelodysplastic syndrome (MDS), is now supported by genetic testing in
      selected cases. However, as the initial suspicion and primary diagnosis of the
      disease still largely relies on morphological features and numbers of
      hematopoietic cells, the establishment of a uniform diagnostic basis, especially
      for cell morphology, is essential. In this study, we collected nearly 100,000
      hematopoietic cell images from 499 peripheral blood smear specimens from patients
      with MDS and used these to evaluate the standardization of morphological
      classification by medical technologists. The observers in this study ranged
      between two to eleven for each image, and the images were classified according to
      MDS criteria through a web-based system. We found considerable inter-observer
      variance in the assessment of dysplastic features. Observers did not recognize
      cytoplasmic hypo-granularity unless almost all granules in neutrophils were
      absent. Pseudo Pelger-Huet anomalies were also often overlooked, except for cells
      with a very typical "pince-nez" appearance. Taken together, this study suggests a
      requirement for further standardization in terms of morphological cell
      classification, and a need for the development of automatic cell classification
      supporting devices for the accurate diagnosis of MDS.

PMID- 29656216
TI  - Insights into cell penetrating peptide conjugated gold nanoparticles for
      internalization into bacterial cells.
AB  - Gold nanoparticles (AuNPs) functionalized with different biomolecules find
      extensive application in therapy, clinical diagnosis and biomedical imaging.
      Herein, two derivatives of TAT peptide with sequences YGRKKRRQRRR and YGRKKRRQRRR
      (beta-ala)3-Cys-amide were conjugated with tannic acid capped gold nanoparticles
      which acted as a carrier for cell penetrating peptides (CPPs) into the bacterial
      cells. The interaction of YGRKKRRQRRR peptide with AuNPs was non-covalent in
      nature whereas YGRKKRRQRRR-(beta-ala)3-Cys-amide interacted covalently with the
      AuNPs due to presence of thiol group in cysteine which bind strongly to gold
      nanoparticles surface. Further, tannic acid functionalised AuNPs conjugated CPPs
      constructs were duly characterized using critical flocculation essay test, UV
      visible and TEM. FITC was tagged over AuNPs-CPPs in order to study the
      intracellular distribution using confocal microscopy. The confocal results
      revealed that nanoconjugates (AuNP-CPPs) of 5 nm diameter exhibited strong
      fluorescent signal in Gram positive and Gram negative bacterial strains. The
      present method can also be used for the killing of bacterial cells using photo
      thermal therapy and therefore can be highly useful for targeting multi-drug
      resistant bacteria.

PMID- 29656217
TI  - Religiosity and interpersonal problems explain individual differences in self
      esteem among young adults with child maltreatment experiences.
AB  - Child maltreatment can have a lasting impact, which is why it is important to
      understand factors that may exacerbate or mitigate self-esteem difficulties in
      adulthood. Although there is tremendous benefit that can come from religion and
      spirituality, few studies examine religious views after child maltreatment.
      Subsequent interpersonal difficulties may also affect self-esteem in maltreatment
      survivors. This study sought to examine interpersonal problems and religiosity as
      mediators in the link between childhood maltreatment and self-esteem in
      adulthood. The study recruited 718 women (M = 19.53 years) from a large public
      university. Participants completed questionnaires related to child abuse and
      neglect, interpersonal problems, religiosity, and self-esteem. Results
      demonstrated that all forms of maltreatment were associated with negative views
      of God and with more interpersonal difficulties. Viewing God as a punishing
      figure mediated the relationship between childhood emotional abuse and low adult
      self-esteem, along with several areas associated with interpersonal problems.
      Further, for both child emotional neglect and physical abuse, viewing God as less
      supportive mediated the relationship between child maltreatment and low adult
      self-esteem. The results may help in intervention for child maltreatment
      survivors by increasing awareness of the importance of religiosity in treatment
      to self-esteem issues in both childhood and adulthood.

PMID- 29656218
TI  - Improved hypocrellin A production in Shiraia bambusicola by light-dark shift.
AB  - Hypocrellin A (HA) is a major bioactive perylenequinone from the fruiting body of
      Shiraia bambusicola used for the treatment of skin diseases and developed as a
      photodynamic therapy (PDT) agent against cancers and viruses. The mycelial
      culture of S. bambusicola under dark is a biotechnological alternative for HA
      production but with low yield. In this study, light and dark conditions were
      investigated to develop effective elicitation on HA production in the cultures.
      Our results showed the constant light at 200 lx stimulated HA production without
      any growth retardation of mycelia. A light/dark shift (24: 24 h) not only
      increased HA content in mycelia by 65%, but stimulated HA release into the medium
      with the highest total HA production 181.67 mg/L on day 8, about 73% increase
      over the dark control. Moreover, light/dark shifting induced the formation of
      smaller and more compact fungal pellets, suggesting a new effective strategy for
      large-scale production of HA in mycelium cultures. The light/dark shift up
      regulated the expression levels of two reactive oxygen species (ROS) related
      genes including superoxide-generating NADPH oxidase (Nox) and cytochrome c
      peroxidase (CCP), and induced the generation of ROS. With the treatment of
      vitamin C, we found that ROS was involved in the up-regulated expression of key
      biosynthetical genes for hypocrellins and improved HA production. These results
      provide a basis for understanding the influence of light/dark shift on fungal
      metabolism and the application of a novel strategy for enhancing HA production in
      submerged Shiraia cultures.

PMID- 29656219
TI  - An improved green synthesis method and Escherichia coli antibacterial activity of
      silver nanoparticles.
AB  - Silver nanoparticles (Ag NPs) were synthesized by an improved green synthesis
      method via a photo-reduction process using low-power UV light in the presence of
      poly (vinyl pyrrolidone) (PVP) as the surface stabilizer. The effective synthesis
      process was achieved by optimized synthesis parameters such as C2H5OH: H2O ratio,
      AgNO3: PVP ratio, pH value, and reducing time. The formation of Ag NPs was
      identified by Ultraviolet-visible (UV-vis) absorption spectra, X-ray diffraction
      pattern (XRD) and Fourier transform infrared spectroscopy (FTIR) spectra. Ag NPs
      were crystallized according to (111), (200), and (220) planes of the face
      centered cubic. The transmission electron microscopy (TEM) image showed that the
      morphology of Ag NPs was uniform spherical with the average particle size of 16
      +/- 2 nm. The results of XRD pattern, TEM image, and dynamic light scattering
      (DLS) analysis proved that Ag crystals with uniform size were formed after the
      reduction process. The mechanism of the formation of Ag NPs was proposed and
      confirmed by FTIR spectra. The antibacterial activity of Ag NPs against
      Escherichia coli (E. coli) was tested and approximately 100% of E. coli was
      eliminated by Ag NPs 35 ppm. In the future, this study can become a new process
      for the application of Ag NPs as an antibiotic in the industrial scale.

PMID- 29656220
TI  - Synergistic effect of the combined bio-fungicides epsilon-poly-l-lysine and
      chitooligosaccharide in controlling grey mould (Botrytis cinerea) in tomatoes.
AB  - The antifungal properties and the induction of resistance by epsilon-poly-l
      lysine (epsilon-PL) and chitooligosaccharide (COS) were examined to find an
      alternative to synthetic fungicides currently used in the control of the
      devastating fungal pathogen Botrytis cinerea, the causal agent of grey mould
      disease of tomatoes. As presented herein, this combined treatment (200 mg/L
      epsilon-PL + 400 mg/L COS) was found to have optimal in vitro antifungal
      activities, achieving an inhibition rate of 90.22%. In vivo assays with these
      combined bio-fungicides, under greenhouse conditions using susceptible tomato
      plants, demonstrated good protection against severe grey mould. In field tests,
      the combined bio-fungicides had a control effect of up to 66.67% against tomato
      grey mould. To elucidate the mechanisms of the combined bio-fungicide-induced
      resistance in the tomato, plants were subjected to three treatments: 1)
      inoculation with B. cinerea after spraying with 200 mg/L epsilon-PL alone, 2)
      inoculation with the combined bio-fungicides, and 3) inoculation with 400 mg/L
      COS alone. Compared to the control (sterile water), increases in salicylic acid
      (SA) and jasmonic acid (JA) levels and increased phenylalanine ammonia lyase
      (PAL), peroxidase (POD), and superoxide dismutase (SOD) activities were observed.
      Catalase (CAT) activity and abscisic acid (ABA) and gibberellin (GA) levels
      decreased, particularly in the combined bio-fungicide-treated plants. Altogether,
      these findings reveal that the combined bio-fungicides (200 mg/L epsilon-PL + 400
      mg/L COS) should be an excellent biocontrol agent candidate that combines direct
      antifungal activity against B. cinerea with plant resistance.

PMID- 29656221
TI  - Patellar malalignment treated with modified knee extension training: An
      electromyography study.
AB  - BACKGROUND: Patellar malalignment (PM) in most patients is ascribed to an
      imbalance of peripatellar soft tissue tension. RESEARCH QUESTION: Conservative
      treatment of PM initially with enforced training of the vastus medialis obliquus
      (VMO) has been widely applied. Non-operative techniques for treatment of PM
      require continuing development. METHODS: Thirty healthy young adults participated
      in the study. Two surface electromyography (EMG) electrodes were placed on the
      skin of the dominant lower thigh in each subject: one on the center of the muscle
      belly of the VMO and the other on the symmetric location of the vastus lateralis
      (VL). Maximum of knee extension action (from various angles of knee flexion to
      full extension) was initiated. Tests were conducted with knee flexion decreasing
      by 10 degrees  at each step. Each action was repeated three times, and the
      average value was calculated. The root mean square value of excited muscles in
      the EMG was recorded. The ratio of the VMO to the VL (VMO/VL) was used to
      indicate the effectiveness of the treatment. The knee position varied from 90
      degrees  flexion initially, decreasing by 10 degrees  at each step. RESULTS: Nine
      sets of values were obtained. All extension actions were effective (VMO/VL >1;
      range, 1.23-1.35). The maximal value was observed at 60 degrees  flexion (VMO/VL
      = 1.35). Differences were not significant among the nine groups (p = 0.08,
      ANOVA). SIGNIFICANCE: Using the described knee extension training for
      conservative treatment of PM may be an effective alternative. The technique is
      simple, and the results of our experimental tests are encouraging. This method
      may become another popular and effective technique for treating PM.

PMID- 29656222
TI  - Prolactin Induced Protein (PIP) is a potential biomarker for early stage and
      malignant breast cancer.
AB  - OBJECTIVES: Breast cancer (BC) is the second leading cause of cancer-related
      mortality in women. Bioinformatic analysis and expression screening showed that
      Prolactin Induced Protein (PIP) was differentially expressed in BC. The objective
      of this investigation was to characterize the expression pattern of PIP, an
      aspartyl proteinase, in malignant and non-malignant breast tissues. MATERIALS AND
      METHODS: Real time quantitative PCR was employed to analyze PIP and androgen
      receptor (AR) mRNA levels in BC cell lines and 190 normal tissues and tumor
      samples. The tumor specimens were categorized based on TNM classification,
      anatomic stage, histologic grade and molecular subtype and expression pattern
      evaluated. To detect protein levels, immunohistochemistry followed by semi
      quantitative scoring was employed in the examination of 517 normal, benign, and
      invasive BC tissues. RESULTS: We observed substantial downregulation of PIP
      transcription in cancer samples compared to normal breast tissue. mRNA levels
      were significantly downregulated (93 fold, P < 0.005) in advanced grades compared
      to lower grades. Transcript levels were also significantly lower (22 fold, P <
      0.05) in triple negative tumors compared to hormone receptor positive tumors.
      Significant downregulation was observed in early stage samples of triple negative
      and hormone receptor positive tumors. Though PIP protein showed a wide range of
      expression levels in BC, early stage samples showed significant downregulation.
      CONCLUSIONS: PIP mRNA is significantly downregulated in early stage BC compared
      to normal breast tissue. Consequently, low PIP mRNA expression in BC tissues
      could potentially be used as a tissue based biomarker to assist pathologists in
      confirmation of early stage BC diagnosis.

PMID- 29656223
TI  - Delay of adjuvant radiotherapy due to postoperative complications after
      oncoplastic breast conserving surgery.
AB  - BACKGROUND: In the past a mastectomy was the first approach of treating breast
      cancer. Oncoplastic techniques combined with breast conserving surgery (BCS) and
      radiotherapy has become an alternative to mastectomy in patients with non
      metastasized breast cancer. The aim of this study was to analyse the amount and
      types of complications occurring after oncoplastic BCS before and after adjuvant
      radiotherapy and the delay of adjuvant therapy due to the complications. METHOD:
      A retrospective study based on all patients who received immediate oncoplastic
      BCS by a plastic surgeon at two medical hospitals in The Netherlands between 2013
      and 2015. (n = 150). The performed oncoplastic BCS techniques were the primary
      outcome measures. In particular major complications with the need for antibiotics
      or surgical intervention. A one-year follow-up was achieved for all patients.
      RESULTS: 52% of the 150 included patients received an oncoplastic BCS through the
      reduction pattern, 35% with a LICAP and 10% with an AICAP. Complications occurred
      in 37.5% of the patients, 10% of the patients needed treatment with antibiotics
      and in 6.6% of the patients a revision operation was indicated. 79.6% of all
      postoperative complications occurred before the start of adjuvant radiotherapy.
      In 8.2% of the patients the adjuvant radiotherapy had to be delayed due to a
      complication. CONCLUSION: This study provides a detailed overview of the used
      techniques of oncoplastic BCS and their postoperative complications. Most
      complications occurred before the start of the adjuvant radiotherapy. Just a
      small amount caused a delay for the radiotherapy to start.

PMID- 29656224
TI  - Compartmentalization of the plasma membrane.
AB  - The compartmentalization of the plasma membrane is essential for cells to perform
      specialized biochemical functions, in particular those responsible for
      intracellular and intercellular signaling pathways. Study of membrane
      compartmentalization requires state-of-the-art imaging tools that can reveal
      dynamics of individual molecules with high spatial and temporal resolution. In
      addition, quantitative analyses are employed to identify transient changes in
      molecule dynamics. In this review, membrane compartments are classified as stable
      domains, transient compartments, or nanodomains where proteins aggregate.
      Interestingly, in most cases, the cortical cytoskeleton plays important roles.
      Recent studies of the membrane-cytoskeleton interface are providing new insights
      about membrane organization involving a scale-free self-similar fractal structure
      and cytoskeleton active processes coupled to membrane dynamics.

PMID- 29656225
TI  - Biodegradation of acrylamide by a novel isolate, Cupriavidus oxalaticus ICTDB921:
      Identification and characterization of the acrylamidase produced.
AB  - Acrylamide is neurotoxic, genotoxic, teratogenic and carcinogenic. Its widespread
      use in various industrial processes leads to environmental contamination.
      Acrylamidase produced by certain bacteria degrade acrylamide to acrylic acid and
      ammonia. The present study details the isolation and identification of soil
      bacterium which could degrade acrylamide. Among the 18 acrylamide-degrading
      isolates tested, isolate ICTDB921 demonstrated superior acrylamide degradation
      which was confirmed by HPLC, FTIR and GC-MS. The partial 16S rRNA sequencing
      confirmed the isolate to be Cupriavidus oxalaticus ICTDB921, which showed highest
      growth at 60 mM acrylamide, neutral pH and 30  degrees C. The kinetic model
      predictions were consistent with experimental results. The acrylamidase from this
      isolate showed potency at pH (6-8) and temperatures (30-60  degrees C), with
      reasonable pH (6-8) and thermal stability (upto 60  degrees C). The enzyme was
      stable against most metal ions and amino acids, and also degraded other aliphatic
      amides, demonstrating its potential in remediation of acrylamide from the
      environment and food systems.

PMID- 29656226
TI  - Stable carbon isotope fractionation of chlorinated ethenes by a microbial
      consortium containing multiple dechlorinating genes.
AB  - The study aimed to determine the possible contribution of specific growth
      conditions and community structures to variable carbon enrichment factors (E
      carbon) values for the degradation of chlorinated ethenes (CEs) by a bacterial
      consortium with multiple dechlorinating genes. E-carbon values for
      trichloroethylene, cis-1,2-dichloroethylene, and vinyl chloride were -7.24% +/-
      0.59%, -14.6% +/- 1.71%, and -21.1% +/- 1.14%, respectively, during their
      degradation by a microbial consortium containing multiple dechlorinating genes
      including tceA and vcrA. The E-carbon values of all CEs were not greatly affected
      by changes in growth conditions and community structures, which directly or
      indirectly affected reductive dechlorination of CEs by this consortium. Stability
      analysis provided evidence that the presence of multiple dechlorinating genes
      within a microbial consortium had little effect on carbon isotope fractionation,
      as long as the genes have definite, non-overlapping functions.

PMID- 29656227
TI  - Removal of hexavalent chromium from aqueous solution by different surface
      modified biochars: Acid washing, nanoscale zero-valent iron and ferric iron
      loading.
AB  - Willow residue biochar (BC) and modified biochars (hydrochloric acid washing
      (HBC), HBC loaded with nanoscale zero-valent iron (nZVI-HBC), and HBC loaded with
      ferric iron (Fe3+-HBC)) after aging were used for aqueous Cr(VI) removal. HBC
      (>98.67%), nZVI-HBC (>98.86%), and Fe3+-HBC (>99.64%) kept high Cr(VI) removal
      rates under the acidic conditions within a wide pH range (<7.0), indicating their
      good adaptability to pH change because of aging. Cr(VI) reduction to Cr(III) was
      the dominant removal mechanism. The formation of COOH on BC, HBC, and nZVI-HBC
      indicates the oxidation of surface functional groups by Cr(VI) and simultaneous
      Cr(VI) reduction. The disappearance of nZVI peaks indicates the reduction of
      Cr(VI) to Cr(III) by nZVI. The color reaction result demonstrated that the
      converted Fe2+ in Fe3+-HBC contributed to Cr(VI) reduction. Taking into account
      the removal efficiency, recyclability, cost, preparation process, and stability
      of adsorbents, Fe3+-HBC was recommended for Cr(VI) removal.

PMID- 29656228
TI  - Generating cycle flow between dark and light zones with double paddlewheels to
      improve microalgal growth in a flat plate photo-bioreactor.
AB  - Double paddlewheels were proposed to generate cycle flow for increasing
      horizontal fluid velocity between dark and light zones in a flat plate photo
      bioreactor, which strengthened the mass transfer and the mixing effect to improve
      microalgal growth with 15% CO2. Numerical fluid dynamics were used to simulate
      the cycle flow field with double paddlewheels. The local flow field measured with
      particle image velocimetry fitted well with the numerical simulation results. The
      horizontal fluid velocity in the photo-bioreactor was markedly increased from 5.8
      * 10-5 m/s to 0.45 m/s with the rotation of double paddlewheels, resulting in a
      decreased dark/light cycle period. Therefore, bubble formation time and diameter
      reduced by 24.4% and 27.4%, respectively. Meanwhile, solution mixing time reduced
      by 31.3% and mass transfer coefficient increased by 41.2%. The biomass yield of
      microalgae Nannochloropsis Oceanic increased by 127.1% with double paddlewheels
      under 15% CO2 condition.

PMID- 29656229
TI  - Unveiling the mechanism of the promising two-dimensional photoswitch -
      Hemithioindigo.
AB  - The control of internal molecular motions by outside stimuli is a decisive task
      in the construction of functional molecules and molecular machines. Light-induced
      intramolecular rotations of photoswitches have attracted increasing research
      interests because of the high stability and high reversibility of photoswitches.
      Recently, Henry et al. reported an unprecedented two-dimensional controlled
      photoswitch, the hemithioindigo (HTI) derivative Z1, whose single bond rotation
      in dimethyl sulphoxide (DMSO) solvent and double bond rotation in cyclohexane
      solvent can be induced by visible light (J. Am. Chem. Soc. 2016, 138, 12,219).
      Here we investigate the intramolecular rotations of the HTI and Z1 in different
      polar solvents by time-dependent density functional theory (TDDFT) and
      Nonadiabatic dynamic simulations. Due to the steric hindrance between methyl and
      thioindigo fragment, the rotations of Z1 in the excited state are obstructed.
      Interestingly, the HTI exhibits two distinct rotation paths in DMSO and
      cyclohexane solvents at about 50fs. The intermolecular hydrogen bonds between HTI
      and DMSO play an important role in the rotation of HTI in DMSO solvent.
      Therefore, the HTI is a more promising two-dimensional photoswitch compared with
      the Z1. Our finding is thus of fundamental importance to understand the
      mechanisms of this class of photoswitches and design complex molecular behavior.

PMID- 29656230
TI  - Multifractal approach for delineating uranium anomalies related to phosphatic
      deposits in Area-3, Northern Palmyrides, Syria.
AB  - Multifractal Concentration-Number (C-N) modeling approach has been developed and
      applied to Airborne Gamma Spectrometry (AGS) data related to Area-3, Northern
      Palmyrides, Syria. The application of the multifractal approach basically aimed
      at separating uranium anomalies from background. The AGS technique has been
      applied for uranium exploration in Syria, where four radioactive parameters were
      recorded, T.C, eU, eTh, and K%. Log-log plots practiced on those radioactive
      variables indicate the presence of different uranium anomaly ranges. Those
      radioactive ranges have been verified and controlled by both geology field and
      surface spectrometric gamma sample rocks analysis. The area range of 5.37-13.20
      eU includes uranium concentration more than 120 ppm, The area range of 2.95-5.37
      eU includes uranium concentration of 50 ppm, and the area range of 1.40-2.95 eU
      includes uranium concentration of 7 ppm. Positive correlation has been
      consequently found between radioactive anomalous eU ranges and uranium
      concentrations. Such correlation indicates the importance of multi fractal
      approach to be extensively used as a fractal analysis-smart sampling tool in
      phosphate and uranium prospecting programs, where a positive correlation between
      phosphate content, radioactivity and uranium concentration exist.

PMID- 29656231
TI  - Simulated response of a multi-element thick gas electron multiplier-based
      microdosimeter to high energy neutrons.
AB  - The response of a microdosimeter for neutrons above 14 MeV is investigated. The
      mean quality factors and dose-equivalents are determined using lineal energy
      distributions calculated by Monte Carlo simulations (Geant4 toolkit). From 14 MeV
      to 5 GeV, the mean quality factors were found to vary between 6.00 and 9.30 and
      the dose-equivalents were in agreement with the true ambient dose-equivalent at
      the depth of 10 mm inside the ICRU sphere, H*(10). An energy-independent dose
      equivalent response around a median value of 0.86 within 22% uncertainty was
      obtained. Therefore, the microdosimeter is appropriate for dose-equivalent
      measurement of high-energy neutrons.

PMID- 29656232
TI  - Gallium incorporation into phosphate based glasses: Bulk and thin film
      properties.
AB  - The osteogenic ions Ca2+, P5+, Mg2+, and antimicrobial ion Ga3+ were homogenously
      dispersed into a 1.45 um thick phosphate glass coating by plasma assisted
      sputtering onto commercially pure grade titanium. The objective was to deliver
      therapeutic ions in orthopaedic/dental implants such as cementeless
      endoprostheses or dental screws. The hardness 4.7 GPa and elastic modulus 69.7
      GPa, of the coating were comparable to plasma sprayed hydroxyapatite/dental
      enamel, whilst superseding femoral cortical bone. To investigate the
      manufacturing challenge of translation from a target to vapour condensed coating,
      structural/compositional properties of the target (P51MQ) were compared to the
      coating (P40PVD) and a melt-quenched equivalent (P40MQ). Following condensation
      from P51MQ to P40PVD, P2O5 content reduced from 48.9 to 40.5 mol%. This
      depolymerisation and reduction in the P-O-P bridging oxygen content as determined
      by 31P NMR, FTIR and Raman spectroscopy techniques was attributed to a decrease
      in the P2O5 network former and increases in alkali/alkali-earth cations. P40PVD
      appeared denser (3.47 vs. 2.70 g cm-3) and more polymerised than it's
      compositionally equivalent P40MQ, showing that structure/ mechanical properties
      were affected by manufacturing route.

PMID- 29656233
TI  - Droplet based vitrification for cell aggregates: Numerical analysis.
AB  - Cell aggregates represent the main format of cells existing in vivo and have been
      widely used as tissue and disease models in vitro. Nevertheless, the preservation
      of cell aggregates while maintaining their functionalities for off-the-shelf
      applications is still challenging. Among various preservation methods, droplet
      based vitrification exhibits superior advantages for the cryopreservation of cell
      aggregates; however, the physical mechanisms underlying droplet-based
      vitrification of cell aggregate using this method remain elusive. To address this
      issue, we proposed a voronoi model to construct two-dimensional geometric
      morphologies of cell aggregates and established a coupled physical model to
      describe the diffusion, heat transfer and crystallization processes during
      vitrification. Based on these models, we performed a numerical study on the
      variation and distribution of cryoprotectant (CPA) concentration, temperature and
      crystallization in cell aggregates during droplet-based vitrification. The
      results show that although cell membrane is not an obvious barrier in heat
      transfer, it affects the diffusion of CPA remarkably as a biologic film and thus
      the following crystallization in cell aggregates. The effective protection of CPA
      during vitrification occurs during the initial stage of CPA diffusion, thus a
      longer CPA loading time does not necessarily lead to significant decrease in
      crystallization, but rather may induce more toxicity to cells.

PMID- 29656234
TI  - Intramasseteric Schwanoma mimicking an isolated cheek mass: Case report and
      review of literature.
AB  - INTRODUCTION: Schwannoma is a benign well circumscribed tumor of the nerve sheath
      and it is mostly localized in the head and neck. Intramasseteric schwannoma
      represents a very rare entity and a few cases have been described in the
      literature. PRESENTATION OF CASE: We present a case of an isolated, asymptomatic
      and slowly progressive right cheek tumor in a middle aged man. Although multiple
      investigations, including neck scanner and fine needle aspiration, were done, the
      diagnosis was obscure and difficult before definite surgical resection. Surgery
      showed an isolated and well-defined tumor inside the masseter muscle which was
      completely resected. Histopathologic finding confirmed the diagnosis of
      schwannoma with the characteristic Antoni A and Antoni B cells. DISCUSSION: Among
      benign tumors of the peripheral nerves, schwannoma is a specific type that
      originates from Schwann cells. It is typically slowly growing, neoplasm that is
      displacing neural structures without direct invasion. History, physical
      examination, fine needle aspiration, and magnetic resonance imaging are used as
      diagnostic modalities, however definitive diagnosis and identification of the
      affected nerve are often difficult up to the time of surgery. CONCLUSION: Herby
      we describe a very rare localization of schwannoma arising from masseter muscle
      in a 30 year old man who presents with painless neck mass. This rare entity
      should be considered in the differential diagnosis in any patient presented with
      cheek mass.

PMID- 29656235
TI  - Effective cancer immunotherapy in mice by polyIC-imiquimod complexes and
      engineered magnetic nanoparticles.
AB  - Encouraging results are emerging from systems that exploit Toll like receptor
      (TLR) signaling, nanotechnology, checkpoint inhibition and molecular imaging for
      cancer immunotherapy. A major remaining challenge is developing effective,
      durable and tumour-specific immune responses without systemic toxicity. Here, we
      report a simple and versatile system based on synergistic activation of immune
      responses and direct cancer cell killing by combined TLR ligation using polyIC as
      TLR3 and imiquimod (R837) as TLR7 agonist, in combination with the model antigen
      ovalbumin (OVA) and phospholipid micelles loaded with zinc-doped iron oxide
      magnetic nanoparticles (MNPs). The combination of TLR agonists triggered a strong
      innate immune response in the lymph nodes (LNs) without systemic release of pro
      inflammatory cytokines. The vaccines showed excellent efficacy against aggressive
      B16-F10 melanoma cells expressing OVA, which was improved with immune checkpoint
      abrogation of the immunosuppressive programmed death-ligand 1 (PD-L1) at the
      level of the cancer cells. By magnetic resonance (MR) and nuclear imaging we
      could track the vaccine migration from the site of injection to LNs and tumour.
      Overall, we show this synergistic TLR agonists and their combination with MNPs
      and immune checkpoint blockade to have considerable potential for preclinical and
      clinical development of vaccines for cancer immunotherapy.

PMID- 29656236
TI  - Advancing systems immunology through data-driven statistical analysis.
AB  - Systems biology provides an effective approach to decipher, predict, and
      ultimately manipulate the complex and inter-connected networks that regulate the
      immune system. Advances in high-throughput, multiplexed experimental techniques
      have increased the availability of proteomic and transcriptomic immunological
      datasets, and as a result, have also accelerated the development of new data
      driven computational algorithms to extract biological insight from these data.
      This review highlights how data-driven statistical models have been used to
      characterize immune cell subsets and their functions, to map the signaling and
      intercellular networks that regulate immune responses, and to connect immune cell
      states to disease outcomes to generate hypotheses for novel therapeutic
      strategies. We focus on recent advances in evaluating immune cell responses
      following viral infection and in the tumor microenvironment, which hold promise
      for improving vaccines, antiviral and cancer immunotherapy.

PMID- 29656238
TI  - Terminal deoxynucleotidyltransferase: the story of an untemplated DNA polymerase
      capable of DNA bridging and templated synthesis across strands.
AB  - Terminal deoxynucleotidyltransferase (TdT) is a member of the polX family which
      is involved in DNA repair. It has been known for years as an untemplated DNA
      polymerase used during V(D)J recombination to generate diversity at the CDR3
      region of immunoglobulins and T-cell receptors. Recently, however, TdT was
      crystallized in the presence of a complete DNA synapsis made of two double
      stranded DNA (dsDNA), each with a 3' protruding end, and overlapping with only
      one micro-homology base-pair, thus giving structural insight for the first time
      into DNA synthesis across strands. It was subsequently shown that TdT indeed has
      an in trans template-dependent activity in the presence of an excess of the
      downstream DNA duplex. A possible biological role of this dual activity is
      discussed.

PMID- 29656237
TI  - Vascularized microfluidic organ-chips for drug screening, disease models and
      tissue engineering.
AB  - Vascularization of micro-tissues in vitro has enabled formation of tissues larger
      than those limited by diffusion with appropriate nutrient/gas exchange as well as
      waste elimination. Furthermore, angiocrine signaling from the vasculature may be
      essential in mimicking organ-level functions in these micro-tissues. In drug
      screening applications, the presence of an appropriate blood-organ barrier in the
      form of a vasculature and its supporting cells (pericytes, appropriate stromal
      cells) may be essential to reproducing organ-scale drug delivery
      pharmacokinetics. Cutting-edge techniques including 3D bioprinting and in vitro
      angiogenesis and vasculogenesis could be applied to vascularize a range of
      tissues and organoids. Herein, we describe the latest developments in
      vascularization and prevascularization of micro-tissues and provide an outlook on
      potential future strategies.

PMID- 29656239
TI  - Mechanical alterations of the bone-cartilage unit in a rabbit model of early
      osteoarthrosis.
AB  - OBJECTIVE: The purpose of this study was to assess mechanical properties along
      with microstructural modifications of the hyaline cartilage (HC), calcified
      cartilage (CC) and cortical plate (Ct.Pt), in an anterior cruciate ligament
      transection (ACLT) model. Medial femoral condyles of six healthy rabbits (control
      group) and of six ACLT rabbits 6 weeks after OA induction were explanted. The
      zone of interest (ZOI) for all experiments was defined as the weight bearing
      areas of the samples. Biomechanical properties were measured using
      nanoindentation and morphological changes were evaluated using biphotonic
      confocal microscopy (BCM). RESULTS: All rabbits of the ACLT group displayed early
      PTOA. The results indicate an overall decrease in the mechanical properties of
      the HC, CC and Ct.Pt in the ACLT group. The average equilibrium modulus and
      elastic fraction of the HC decreased by 42% and 35%, respectively, compared with
      control group. The elastic moduli of the CC and Ct.Pt decreased by 37% and 16%,
      respectively, compared with control group. A stiffness gradient between CC and
      Ct.Pt appeared in the ACLT group. The irregularity of the cement line, quantified
      by its tortuosity in BCM images, was accentuated in the ACLT group compared with
      the control group. CONCLUSIONS: In the ACLT model, weight-bearing stress was
      modified in the ZOI. This disruption of the stress pattern induced alterations of
      the tissues composing the bone-cartilage unit. In term of mechanical properties,
      all tissues exhibited changes. The most affected tissue was the most superficial:
      hyaline cartilage displayed the strongest relative decrease (42%) followed by
      calcified cartilage (37%) and cortical plate was slightly modified (16%). This
      supports the hypotheses that PTOA initiates in the hyaline cartilage.

PMID- 29656240
TI  - Packing of muscles in the rabbit shank influences three-dimensional architecture
      of M. soleus.
AB  - Isolated and packed muscles (e.g. in the calf) exhibit different three
      dimensional muscle shapes. In packed muscles, cross-sections are more angular
      compared to the more elliptical ones in isolated muscles. As far as we know, it
      has not been examined yet, whether the shape of the muscle in its packed
      condition influences its internal arrangement of muscle fascicles and accordingly
      the contraction behavior in comparison to the isolated condition. To evaluate the
      impact of muscle packing, we examined the three-dimensional muscle architecture
      of isolated and packed rabbit M. soleus for different ankle angles (65 degrees ,
      75 degrees , 85 degrees , 90 degrees , and 95 degrees ) using manual digitization
      (MicroScribe(r) MLX). In general, significantly increased values of pennation
      angle and fascicle curvature were found in packed compared to isolated M. soleus
      (except for fascicle curvature at 90 degrees  ankle angle). On average, fascicle
      length of isolated muscles exceeded fascicle lengths of packed muscles by 2.6%.
      Reduction of pennation angle in the packed condition had only marginal influence
      on force generation (about 1% of maximum isometric force) in longitudinal
      direction (along the line of action) although an increase of transversal force
      component (perpendicular to the line of action) of about 26% is expected. Results
      of this study provide initial evidence that muscle packing limits maximum muscle
      performance observed in isolated M. soleus. Besides an enhanced understanding of
      the impact of muscle packing on architectural parameters, the outcomes of this
      study are essential for realistic three-dimensional muscle modeling and model
      validation.

PMID- 29656241
TI  - Material properties of ultra-high molecular weight polyethylene: Comparison of
      tension, compression, nanomechanics and microstructure across clinical
      formulations.
AB  - This is the first study to simultaneously measure material properties in tension,
      compression, nanoindentation as well as microstructure (crystallinity and
      lamellar level properties) across a wide variety of clinically relevant ultra
      high molecular weight polyethylene (UHMWPE) formulations. Methodologies for the
      measurement of UHMWPE mechanical properties-namely elastic modulus, yield stress,
      yield strain, ultimate strength, energetic toughness, Poisson's ratio, hardness
      and constitutive variables-are evaluated. Engineering stress-strain behavior is
      compared to true stress-strain behavior for UHMWPE across a range of cross
      linking and antioxidant chemistry. The tensile mechanical properties and
      constitutive behavior of UHMWPE are affected by resin type, antioxidant source
      and degree of cross-linking. Poisson's ratio is shown to be affected by resin
      type, antioxidant addition, and cross-linking dosage. Relationships between bulk
      mechanical properties from different measurement methodologies as well as
      microstructure are analyzed across all material formulations using Spearman rank
      correlation coefficients. Modulus and yield strength correlate in both tension
      and compression. Similarly, tensile and compressive properties including modulus
      and yield strength correlate strongly with crystallinity (Xc) and lamellar
      thickness (D). This work has broad application and provides a basis for
      interpreting the mechanical behavior of UHMWPE used in orthopedic implants.

PMID- 29656242
TI  - A highly sensitive electrochemical biosensor for phenol derivatives using a
      graphene oxide-modified tyrosinase electrode.
AB  - The fabrication, characterization and analytical performance were investigated
      for a phenol biosensor based on the covalent bonding of tyrosinase (TYR) onto a
      graphene oxide (GO)-modified glassy carbon electrode (GCE) via glutaraldehyde
      (GA). The surface morphology of the modified electrode was studied by atomic
      force microscope (AFM) and field-emission scanning electron microscopy (FE-SEM).
      The fabricated TYR/GA/GO/GCE biosensor showed very good stability,
      reproducibility, sensitivity and practical usage. The catechol biosensor
      exhibited a wide sensing linear range from 5*10-8M to 5*10-5M, a lower detection
      limit of 3*10-8M, a current maximum (Imax) of 65.8MUA and an apparent Michaelis
      constant (Kmapp) of 169.9MUM.

PMID- 29656243
TI  - Different permeabilization patterns of splenocytes and thymocytes to combination
      of pulsed electric and magnetic field treatments.
AB  - Genetic manipulation of T cells is frequently inefficient, however, when combined
      with physical methods (i.e. electroporation) a promising alliance with
      immunotherapy can be formed. This study presents new data on permeabilization of
      murine thymocytes and splenocytes as a T cell model using pulsed electric (PEF)
      and electromagnetic field (EMF). The 300ns, 500ns, 2MUs and 100MUs pulse bursts
      in a broad range of PEF 0-8kV/cm were applied separately and in combination with
      3.3T, 0.2kV/cm EMF pulses. The permeabilization efficiency was evaluated using
      fluorescent dye (YO-PRO-1) and flow cytometry. It was shown that a >14% increase
      in thymocytes permeabilization is achieved when electroporation is applied in
      combination with EMF, however splenocytes responded in a different manner - a
      statistically significant (P<0.05) reduction in permeabilization was observed.
      The cytokine secretion patterns were mainly unaltered independently on the
      applied treatment parameters determined by secretion of IFNgamma, IL-4 and IL-17 
      the main cytokines of Th1, Th2 and Th17 cells. The results of this study are
      useful for development of pulsed power protocols for effective genetic
      modification of T cells.

PMID- 29656244
TI  - Human organoid cultures: transformative new tools for human virus studies.
AB  - Studies of human infectious diseases have been limited by the paucity of
      functional models that mimic normal human physiology and pathophysiology. Recent
      advances in the development of multicellular, physiologically active organotypic
      cultures produced from embryonic and pluripotent stem cells, as well as from stem
      cells isolated from biopsies and surgical specimens are allowing unprecedented
      new studies and discoveries about host-microbe interactions. Here, we summarize
      recent developments in the use of organoids for studying human viral pathogens,
      including intestinal infections with human rotavirus, norovirus, enteroviruses
      and adenoviruses (intestinal organoids and enteroids), neuronal infections with
      Zika virus (cerebral organoids) and respiratory infections with respiratory
      syncytial virus in (lung bud organoids). Biologic discovery of host-specific
      genetic and epigenetic factors affecting infection, and responses to infection
      that lead to disease are possible with the use of organoid cultures. Continued
      development to increase the complexity of these cultures by including components
      of the normal host tissue microenvironment such as immune cells, blood vessels
      and microbiome, will facilitate studies on human viral pathogenesis, and advance
      the development of platforms for pre-clinical evaluation of vaccines, antivirals
      and therapeutics.

PMID- 29656246
TI  - Occurrence and ecological risk assessment of organic micropollutants in the lower
      reaches of the Yangtze River, China: A case study of water diversion.
AB  - Water diversion has been increasingly applied to improve water quality in many
      water bodies. However, little is known regarding pollution by organic
      micropollutants (OMPs) in water diversion projects, especially at the supplier,
      and this pollution may threaten the quality of transferred water. In the present
      study, a total of 110 OMPs belonging to seven classes were investigated in water
      and sediment collected from a supplier of the Yangtze River within four water
      diversion projects. A total of 69 and 58 target OMPs were detected in water and
      sediment, respectively, at total concentrations reaching 1041.78 ng/L and 5942.24
      ng/g dry weight (dw). Polycyclic aromatic hydrocarbons (PAHs) and pharmaceuticals
      were the predominant pollutants identified. When preliminarily compared with the
      pollution in the receiving water, the Yangtze River generally exhibited mild OMPs
      pollution and good water quality parameters, implying a clean water source in the
      water diversion project. However, in Zongyang and Fenghuangjing, PAHs pollution
      was more abundant than that in the corresponding receiving water in Chaohu Lake.
      Ammonia nitrogen pollution in the Wangyu River was comparable to that in Taihu
      Lake. These findings imply that water diversion may threaten receiving waters in
      some cases. In addition, the risks of all detected pollutants in both water and
      sediment were assessed. PAHs in water, especially phenanthrene and high-molecular
      weight PAHs, posed high risks to invertebrates, followed by the risks to fish and
      algae. Pharmaceuticals, such as antibiotics and antidepressants, may also pose
      risks to algae and fish at a number of locations. To the best of our knowledge,
      this report is the first to describe OMPs pollution in water diversion projects,
      and the results provide a new perspective regarding the security of water
      diversion projects.

PMID- 29656245
TI  - Individual differences in socioemotional sensitivity are an index of salience
      network function.
AB  - Connectivity in intrinsically connected networks (ICNs) may predict individual
      differences in cognition and behavior. The drastic alterations in socioemotional
      awareness of patients with behavioral variant frontotemporal dementia (bvFTD) are
      presumed to arise from changes in one such ICN, the salience network (SN). We
      examined how individual differences in SN connectivity are reflected in overt
      social behavior in healthy individuals and patients, both to provide
      neuroscientific insight into this key brain-behavior relationship, and to provide
      a practical tool to diagnose patients with early bvFTD. We measured SN functional
      connectivity and socioemotional sensitivity in 65 healthy older adults and 103
      patients in the earliest stage [Clinical Dementia Rating (CDR) Scale score <=1]
      of five neurodegenerative diseases [14 bvFTD, 29 Alzheimer's disease (AD), 20
      progressive supranuclear palsy (PSP), 21 semantic variant primary progressive
      aphasia (svPPA), and 19 non-fluent variant primary progressive aphasia (nfvPPA)].
      All participants underwent resting-state functional imaging and an informant
      described their responsiveness to subtle emotional expressions using the Revised
      Self-Monitoring Scale (RSMS). Higher functional connectivity in the SN,
      predominantly between the right anterior insula (AI) and both "hub" cortical and
      "interoceptive" subcortical nodes, predicted socioemotional sensitivity among
      healthy individuals, showing that socioemotional sensitivity is a behavioral
      marker of SN function, and particularly of right AI functional connectivity. The
      continuity of this relationship in both healthy and neurologically affected
      individuals highlights the role of socioemotional sensitivity as an early
      diagnostic marker of SN connectivity. Clinically, this is particularly important
      for identification of patients in the earliest stage of bvFTD, where the SN is
      selectively vulnerable.

PMID- 29656247
TI  - Distribution, source, and risk of organochlorine pesticides (OCPs) and
      polychlorinated biphenyls (PCBs) in urban and rural soils around the Yellow and
      Bohai Seas, China.
AB  - Between 1945 and 1983, China was the world's largest producer of organochlorine
      pesticides (OCPs) and polychlorinated biphenyls (PCBs), and the second largest
      producer of hexachlorocyclohexanes (HCHs) and dichlorodiphenyltrichloroethanes
      (DDTs). The provinces of Liaoning, Hebei, Tianjin, Shandong, and Jiangsu around
      the Yellow and Bohai Seas have a long history of production and usage of OCPs and
      PCBs. To investigate their residual concentration, distribution, risk level, and
      temporal degradation, 7 OCPs and 7 indicator PCBs were determined in surface
      soils collected around the Yellow and Bohai Seas. Residues of the 7 OCPs and 7
      PCBs were in the range of 5.89-179.96 ng g-1 dry weight (dw) and non-detectable
      (ND)-385.67 ng g-1 dw, respectively. Tianjin and Hebei provinces recorded the
      highest concentrations of OCPs and PCBs, respectively. Moreover, OCPs residues
      had a significant relationship with agriculture and orchard land-use types,
      whereas PCBs residues occurred more in wasteland. Lifetime carcinogenic and non
      carcinogenic risks of OCPs and PCBs through ingestion, inhalation, and dermal
      contact indicated that OCPs and PCBs residues in surface soils are at a low risk
      level.

PMID- 29656248
TI  - Human health risk assessment for nanoparticle-contaminated aquifer systems.
AB  - Nanosized particles (NPs), such as TiO2, Silver, graphene NPs, nanoscale zero
      valent iron, carbon nanotubes, etc., are increasingly used in industrial
      processes, and releases at production plants and from landfills are likely
      scenarios for the next years. As a consequence, appropriate procedures and tools
      to quantify the risks for human health associated to these releases are needed.
      The tiered approach of the standard ASTM procedure (ASTM-E2081-00) is today the
      most applied for human health risk assessment at sites contaminated by chemical
      substances, but it cannot be directly applied to nanoparticles: NP transport
      along migration pathways follows mechanisms significantly different from those of
      chemicals; moreover, also toxicity indicators (namely, reference dose and slope
      factor) are NP-specific. In this work a risk assessment approach modified for NPs
      is proposed, with a specific application at Tier 2 to migration in groundwater.
      The standard ASTM equations are modified to include NP-specific transport
      mechanisms. NPs in natural environments are typically characterized by a
      heterogeneous set of NPs having different size, shape, coating, etc. (all
      properties having a significant impact on both mobility and toxicity). To take
      into account this heterogeneity, the proposed approach divides the NP population
      into classes, each having specific transport and toxicity properties, and
      simulates them as independent species. The approach is finally applied to a test
      case simulating the release of heterogeneous Silver NPs from a landfill. The
      results show that taking into account the size-dependent mobility of the
      particles provides a more accurate result compared to the direct application of
      the standard ASTM procedure. In particular, the latter tends to underestimate the
      overall toxic risk associated to the nP release.

PMID- 29656249
TI  - Mechanism of matrix-bound phosphine production in response to atmospheric
      elevated CO2 in paddy soils.
AB  - To explore the effect of elevated CO2 concentrations ([CO2]) on phosphine
      formation in paddy fields, the matrix-bound phosphine (MBP) content, different
      phosphorus fractions and various carbon forms in soil samples from rice
      cultivation under varying CO2 concentrations of 400 ppm, 550 ppm and 700 ppm by
      indoor simulation experiment were determined. This study showed that MBP
      concentration did not increase significantly with elevated [CO2] over four-week
      cultivation periods of rice seedlings, regardless of soil layers. MBP had a
      significant positive correlation with total phosphorus (TP) and inorganic
      phosphorus (IP), and multiple stepwise linear regression analysis further
      indicated that MBP preservation in neutral paddy soils with depths of 0-20 cm may
      have been due to conversion from FeP and CaP. Based on redundancy analysis and
      forward selection analysis, speculated that the formation of MBP in the neutral
      paddy soils as the response to atmospheric elevated [CO2] was due to two
      processes: (i) FeP transformation affected by the changes of soil respiration
      (SCO2) and TOC was the main precursor for the production of MBP; and (ii) CaP
      transformation resulting from variation in HCO3- was the secondary MBP source.
      The complex combination of these two processes is simultaneously controlled by
      SCO2. In a word, the soil environment in the condition of elevated [CO2] was in
      favor of MBP storage in neutral paddy soils. The results of our study imply that
      atmospheric CO2 participates in and has a certain impact on the global
      biogeochemical cycle of phosphorus.

PMID- 29656250
TI  - Exposure to environmental level phenanthrene induces a NASH-like phenotype in new
      born rat.
AB  - More and more evidence indicates that persistent organic pollutants (POPs) are a
      risk factor for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic
      steatohepatitis (NASH). Phenanthrene (Phe) is a kind of POP which existed
      extensively in the environment, but whose toxicity on mammals has so far received
      less focus. Subcutaneously injection of Phe (0.5, 5, 50 MUg/kg) for 21 days
      induced significant NAFLD/NASH symptoms in new born rats. Exposure to
      environmental levels of Phe decreased body weight and liver-somatic index;
      impaired histology of liver; influenced the peroxisome proliferator-activated
      receptor gamma (PPARgamma) signaling and lipid metabolism in liver; stimulated
      oxidative stress in the rats' liver; induced the variation of NFkappaB pathway
      and liver inflammatory response; and caused liver fibrosis via transforming
      growth factor beta1 (tgfbeta1). We speculated that the subcutaneously injected
      Phe was transferred to the liver through blood circulation, which may have
      induced the elevation of PPARgamma directly or indirectly, leading to liver
      steatosis. Excess lipid, acting as the first hit, stimulated the second hit
      factors - oxidative stress, inflammatory response and lipid peroxidation, and
      finally resulted in steatohepatitis and liver fibrosis.

PMID- 29656251
TI  - Thallium contamination of desert soil in Namibia: Chemical, mineralogical and
      isotopic insights.
AB  - We studied arid desert soils from Namibia (Rosh Pinah) that were contaminated
      with up to 7 mg kg-1 of thallium (Tl) via dust emitted from a local flotation
      tailing dam. Chemical extractions of waste and soil materials indicated that most
      of the Tl is strongly bound, in accordance with X-ray diffraction and X-ray
      absorption spectroscopy data that point to the predominant association of Tl with
      metal sulfides and phyllosilicates. The isotope fractionation factor epsilon205Tl
      of the soil samples (from -0.4 to +3.8) shows a positive linear relationship (R2
      = 0.62) with 1/Tl, indicative for the mixing of two major Tl pools, presumably
      anthropogenic Tl and geogenic Tl. The epsilon205Tl value for the topmost soil
      samples (~+3) closely matches the epsilon205Tl value for post-flotation waste
      particles with a diameter of <0.05 mm, whereas the bulk flotation waste exhibits
      a significantly larger epsilon205Tl value (~+6). These variations are in
      accordance with predominant atmospheric transfer of Tl from the tailings to the
      adjacent soils via fine (dust) particles. The identified minimal Tl alteration in
      soils indicates that only a small part of the Tl could be potentially released
      and passively enter the vegetation, local population and/or food chain in the
      long term. From this viewpoint, Tl does not represent such an important
      environmental concern as other (abundant) contaminants at the locality.
      Furthermore, there could be a relevance for other alkaline desert soils,
      including those where Tl pollution plays a major role.

PMID- 29656252
TI  - Assessing the effect of industrial wastewater on soil properties and
      physiological and nutritional responses of Robinia pseudoacacia, Cercis
      siliquastrum and Caesalpinia gilliesii seedlings.
AB  - The main aim of this study is to investigate the physical and chemical
      properties, including soil salinity, acidity, concentrations of macro-nutrients
      (phosphorus, potassium, and Calcium-Magnesium) and sodium adsorption ratio to the
      soil, physiological and nutritional traits of three plant species including
      Caesalpinia gilliesii, Robinia pseudoacacia, and Cercis siliquastrum. First, some
      sample were taken from the agricultural soils irrigated with wastewater. The
      results of initial soil test revealed that the irrigation with wastewater
      significantly increased sodium adsorption ratio (SAR), electrical conductivity
      (ECe), cation exchange capacity (CEC) of the soil (p < 0.05). Secondly, the
      effect of industrial wastewater on the responses of three plants were
      investigated. According to the results, the highest shoot fresh weight was
      observed in C. gilliesii seedlings treated with T100%, which is 35% higher than
      the control treatment. The highest concentration of shoot phosphorus in the three
      plants was respectively 0.54, 0.72, and 1% in those treated with T100% and 0.41,
      0.48, and 0.83% in the control treatment. The amount of shoot potassium in the
      three plants treated with T100% was respectively 0.84, 0.48, and 1%, while it was
      0.43, 0.4, and 0.1 in the control treatment, respectively (p < 0.05). According
      to the current concerns about increased EC, SAR, and Na in C. gilliesii treated
      with T100%, as compared to the control treatment (50, 386, and 412), and the
      positive effects of wastewater on soil properties (CEC, pH, and K) and morpho
      physiological responses of the plant, it is recommended to use wastewater with
      continuous monitoring to prevent the pollution of water and soil resource.

PMID- 29656253
TI  - Disposal of olive mill wastewater with DC arc plasma method.
AB  - Olive mill wastewater is an industrial waste, generated as a byproduct of olive
      oil production process and generally contains components such as organic matter,
      suspended solids, oil, and grease. Although various methods have been developed
      to achieve the disposal of this industrial wastewater, due to the low cost, the
      most common disposal application is the passive storage in the lagoons. The main
      objective of this study is to reduce pollution parameters in olive mill
      wastewater and draw water to discharge limits by using plasma technology. Plasma
      assisted disposal of olive mill wastewater method could be an alternative
      disposal technique when considering potential utilization of treated water in
      agricultural areas and economic value of flammable plasma gas which is the
      byproduct of disposal process. According to the experimental results, the rates
      of COD (chemical oxygen demand) and BOD (biological oxygen demand) of olive mill
      wastewater are decreased by 94.42% and 95.37%, respectively. The dissolved oxygen
      amount is increased from 0.36 to 6.97 mg/l. In addition, plasma gas with high H2
      content and treated water that can be used in agricultural areas for irrigation
      are obtained from non-dischargeable wastewater.

PMID- 29656254
TI  - Review of national methodologies for rivers' hydromorphological assessment: A
      comparative approach in France, Romania, and Croatia.
AB  - Conducting hydromorphological assessments for evaluating the ecological status of
      rivers is a key requirement of the Directive 2000/60/EC (Water Framework
      Directive - WFD) within European Union (EU) Member States. This paper aims at
      understanding how this requirement was implemented, through an original
      comparative review of methodologies for rivers' hydromorphological assessment in
      three EU Member States, which joined the EU at different times, and with many
      differences in terms of hydrographic features, socio-economic and water
      management systems: France, Romania, and Croatia. More precisely, the paper aims
      at identifying and understanding the main principles guiding the
      hydromorphological assessment methodologies, elements and data used, giving an
      overview of the results of hydromorphological river status assessment, and
      concluding on the stage of hydromorphological assessment implementation. France
      developed numerous methodologies for physical habitat survey since the 1990s and
      it is currently conducting a rigorous hydromorphological field survey, but it
      does not yet have any national methodology for rivers' hydromorphological status
      assessment, nevertheless foreseen for the next cycle of the WFD. Besides, Romania
      and Croatia have already started the assessment of the hydromorphological status
      of rivers within the two cycles of the River Basin Management Plans and are
      making efforts to improve the hydromorphological monitoring activity. The methods
      generally differ in indicators, data used, and spatial scale of analysis, which
      makes it difficult to compare the results of the assessments. Despite a common
      water policy, the methodological dissimilarities seem to be rather usual between
      EU Member States. Therefore, the standardization of methodologies appears to be
      necessary, but the current results could be useful for setting priorities for
      river restoration and for achieving a better status at a national scale.

PMID- 29656255
TI  - Microbial iron reduction as a method for immobilization of a low concentration of
      dissolved cadmium.
AB  - Much attention has been paid to the relationship between microbial iron reduction
      and the behavior of cadmium (Cd) recently, but most previous research has
      employed unrealistically high Cd concentrations (e.g., 2-55 mg L-1) and has
      failed to consider the effects of iron oxides and microbial cells together. We
      investigated the reduction of lepidocrocite by Shewanella oneidensis MR-1 in the
      presence of a low concentration of Cd using batch reactor systems. The results
      showed that with 422 MUg L-1 added dissolved Cd2+, an initial 137 MUg L-1
      decrease in aqueous Cd occurred due to adsorption onto lepidocrocite and that the
      further removal of remaining aqueous Cd occurred only in the system containing
      bacteria. This further decrease in aqueous Cd was unlikely to be caused by
      mineral transformation because the microbial reduction of lepidocrocite resulted
      in particle-size-increased (thus, specific-surface-area-decreased) lepidocrocite,
      and unlikely to be caused by the pH increase to 7.4 induced by iron reduction
      either because a pH-adsorption edge suggested that at pH 7.4, less than 60% of
      aqueous Cd can be adsorbed by lepidocrocite in the reactors. An adsorption
      isotherm showed a significant Cd adsorption capacity by S. oneidensis MR-1 cells,
      and we therefore attributed the further Cd removal to adsorption by S. oneidensis
      MR-1 cells. The results suggest that a realistically low concentration of Cd can
      be immobilized during microbial iron reduction by adsorption on iron oxides and
      microbial cells.

PMID- 29656256
TI  - Phosphatase mediated bioprecipitation of lead as pyromorphite by Achromobacter
      xylosoxidans.
AB  - Achromobacter xylosoxidans strain SJ11, tolerating up to 4.0 mM lead nitrate, in
      a defined minimal medium was isolated from the waste of a battery manufacturing
      industry, Goa, India. Interestingly, it formed white precipitate on exposure to
      lead nitrate which was also evident from scanning electron micrograph (SEM).
      Energy dispersive X-ray spectroscopic analysis revealed the presence of lead
      (48.5% by weight) along with phosphorus and chlorine in the precipitate.
      Transmission electron microscopy (TEM) of bacterial cells clearly refuted the
      possibility of intracellular lead uptake confirming extracellular precipitation
      as a predominant mechanism of lead resistance in this bacterium. The
      extracellular precipitate was further identified as pyromorphite [Pb5(PO4)3Cl] by
      X-ray diffraction analysis. This was also corroborated by fourier transformed
      infrared spectroscopy (FTIR) indicating a significant involvement of phosphate
      groups. Atomic absorption spectroscopic analysis clearly demonstrated that 465.8
      mg g-1 lead was precipitated by the bacterial cells. There was remarkable
      increase of 160% in phosphatase activity suggesting it's important role in lead
      precipitation. This was further substantiated by significant up-regulation of
      phosphatase, CheZ using LC-MS/MS. Therefore phosphatase mediated extracellular
      precipitation of lead as pyromorphite by A. xylosoxidans strain SJ11 clearly
      demonstrated it's potential in bioremediation of lead contaminated environmental
      sites.

PMID- 29656257
TI  - Nutrient-derived environmental impacts in Chinese agriculture during 1978-2015.
AB  - Nitrogen (N) and phosphorus (P) play a critical role in agricultural production
      and cause many environmental disturbances. By combing life cycle assessment (LCA)
      method with the mass balance principle of substance flow analysis (SFA), this
      study establishes a nutrient-derived environmental impact assessment (NEIA) model
      to analyze the environmental impacts caused by nutrient-containing substances of
      agricultural production in China during 1978-2015. The agricultural production
      system is composed of crop farming and livestock breeding, and the environmental
      impacts include energy consumption, global warming, acidification, and
      eutrophication. The results show all these environmental impacts had increased to
      8.22*109 GJ, 5.01*108 t CO2-eq, 2.41*107 t SO2-eq, and 7.18*107 t PO43--eq,
      respectively. It is noted the energy consumption and the climate change caused by
      the crop farming were always higher than those from livestock breeding, which
      were average 60 and two times, respectively. While the acidification and the
      eutrophication were opposite after 1995 and 2000, even they were similar. This
      was mainly due to the high N application including synthetic N fertilizer (from
      1.33*109 GJ to 2.08*109 GJ), applied manure (from 4.94*108 GJ to 5.65*108 GJ) and
      applied crop residue (from 2.94*108 GJ to 5.30*109 GJ), while the synthetic N
      fertilizer was controlled and the livestock expanded rapidly after 1995. Among
      the sub-categories, the three staple crops (rice, wheat, and maize) contributed
      greater environmental impacts, which were about two to 10 times as other crops
      and livestock, due to their high fertilizer uses, sown areas and harvests. While
      the oil crops and fruit consumed the least energies because of their much lower
      fertilizer-use intensities. Pig and poultry especially pig also caused obvious
      effects on environment (even 20 times as other livestock) because of their large
      quantities and excretions, which emitted much higher N2O and P loss resulting in
      much higher climate change, acidification and eutrophication than other
      livestock. Then the study proposes the nutrient management in agricultural
      production by considering crop production, livestock breeding and dietary
      adjustment, so that some valuable experiences can be shared by the stakeholders
      in other Chinese regions.

PMID- 29656258
TI  - Towards a uniform specification of light therapy devices for the treatment of
      affective disorders and use for non-image forming effects: Radiant flux.
AB  - BACKGROUND: For treating affective disorders like SAD, light therapy is used
      although the underlying mechanism explaining this success remains unclear. To
      accelerate the research on defining the light characteristics responsible for
      inducing a specific effect a uniform manner for specifying the irradiance at the
      eye should be defined. This allows a genuine comparison between light-affect
      studies. An important factor impacting the irradiance at the eye are the radiant
      characteristics of the used light therapy device. METHOD: In this study the
      radiant fluxes of five different light therapy devices were measured. The values
      were weighted against the spectral sensitivity of the five photopigments present
      in the human eye. A measurement was taken every five minutes to control for a
      potential stabilizing effect. RESULTS: The results show that all five devices
      show large differences in radiant flux. The devices equipped with blue LED lights
      have a much lower spectral radiant flux than the devices equipped with a
      fluorescent light source or a white LED. The devices with fluorescent lamps
      needed 30 min to stabilize to a constant radiant flux. LIMITATIONS: In this study
      only five devices were measured. Radiant flux is just the first step to identify
      uniform specifications for light therapy devices. CONCLUSIONS: It is recommended
      to provide all five alpha-opic radiant fluxes. Preferably, the devices should
      come with a spectral power distribution of the radiant flux. For the devices
      equipped with a fluorescent lamp it is recommended to provide information on the
      stabilization time.

PMID- 29656259
TI  - Increased coherence-based regional homogeneity in resting-state patients with
      first-episode, drug-naive somatization disorder.
AB  - BACKGROUND: Abnormal neural activity has been observed in patients with
      somatization disorder (SD), especially in brain regions of the default-mode
      network (DMN). In this study, a coherence-based regional homogeneity (Cohe-ReHo)
      approach was used to detect abnormal regional synchronization in patients with
      SD, which might be used to differentiate the patients from the controls. METHODS:
      We recruited 25 patients with SD and 28 healthy controls. The imaging data of the
      participants were analyzed using the Cohe-ReHo approach. LIBSVM (a library for
      support vector machines) was utilized to verify whether abnormal Cohe-ReHo values
      could be applied to separate patients with SD from healthy controls. RESULTS:
      Compared with healthy controls, patients with SD showed an increased Cohe-ReHo in
      the left medial prefrontal cortex/anterior cingulate cortex (MPFC/ACC) (t =
      5.5017, p < 0.001). No correlations were detected between the increased Cohe-ReHo
      values and clinical variables of the patients. The Cohe-ReHo values in the left
      MPFC/ACC could be applied to distinguish patients from controls with a
      sensitivity and a specificity of 84.00% and 85.71%, respectively. CONCLUSIONS: An
      increased Cohe-ReHo was observed in the anterior DMN of the patients and could be
      applied as a marker to distinguish patients from healthy controls. These results
      highlighted the importance of the DMN in the pathophysiology of SD.

PMID- 29656260
TI  - Racial/ethnic differences in the treatment of adolescent major depressive
      disorders (MDD) across healthcare providers participating in the medicaid
      program.
AB  - BACKGROUND: To examine whether racial/ethnic differences in receipt of MDD
      treatment could be explained by the specialty of provider diagnosing the
      adolescent. METHOD: Adolescents (10-20 years-old) with >=2 MDD diagnoses were
      identified using 2005-2007 Medicaid data from Texas. Patients were categorized
      based on the types of provider who gave the initial MDD diagnosis (psychiatrist
      (PSY-I), social worker/psychologist (SWP-I), and primary care physician (PCP-I)).
      Within the sub-cohorts identified by each type of provider, patients were further
      divided by racial/ethnic groups. RESULTS: Of the 13,234-new pediatric MDD cases
      diagnosed, 61% were SWP-I, 33% PSY-I and 6% PCP-I. Results of the analysis using
      general linear multi-level model showed that being first diagnosed by a
      psychiatrist was associated with higher chance of receiving MDD related treatment
      (PCP-I vs. PSY-I (OR: 0.54, 95%CI: 0.4-0.7) and SWP-I vs. PSY-I (OR: 0.17, 95%CI:
      0.1-0.2)). Specifically, regarding the receipt of pharmacotherapy, an interaction
      effect was detected between types of identifying providers and patients'
      race/ethnicity. The analysis stratified by race/ethnicity found Whites received
      comparable treatment regardless being PCP-Is or PSY-Is, while for Hispanics,
      being first identified by a PCP was associated with lower likelihood of receiving
      treatment as compared to being first identified by a psychiatrist. Further
      analysis stratified by provider types showed that a significant racial/ethnic
      variation in medication utilization was observed in PCP-Is, but not in PSY-Is.
      CONCLUSION: For adolescents with MDD, being first diagnosed by a psychiatrist was
      associated with higher treatment rate and reduced racial/ethnic variation in the
      utilization of pharmacotherapy.

PMID- 29656261
TI  - Young adult cognitive ability and subsequent major depression in a cohort of
      666,804 Danish men.
AB  - BACKGROUND: Early life cognitive ability (CA) might influence the risk of
      developing major depression (MD). The aim was to investigate the association
      between young adult CA and subsequent MD in relation to different MD disease
      characteristics. METHODS: Information on CA was assessed at conscription board
      examinations 1957-1984 (mean age 19 years) and information on MD was based on
      hospital diagnosis retrieved from Danish Patient registers 1969-2015.
      Associations between CA and MD were examined using Cox regression analyses.
      RESULTS: A total of 666,804 men (born 1939-1959) were followed and 25,841 (3.9%)
      developed MD during a mean follow-up of 40.8 years. Lower CA was associated with
      an increased risk of incident MD. The association was stronger for early-onset
      (<60 years) (HRper1SDdecrease = 1.23; 95%CI:1.21,1.24) compared to late-onset
      (>=60 years) MD (HRper1SDdecrease = 1.14; 95%CI:1.11,1.16), but CA was not
      related to number of depressive episodes. The association was stronger for single
      depressive episodes (HRper1SDdecrease = 1.21; 95%CI:1.19,1.23) compared to
      recurrent depression (HRper1SDdecrease = 1.13; 95%CI:1.09,1.16), while the
      strength of the association did not differ according to MD disease severity
      (ICD10: mild, moderate, and severe depression). LIMITATIONS: The study sample
      only included men and only MD cases diagnosed at hospital were included which
      limits the generalizability. CONCLUSION: Low CA could be a risk factor for
      especially early onset MD in men, whereas the influence of CA on re-occurrence
      seems less strong. Lower pre-morbid CA increases the risk of MD and should
      therefore be part of the depression risk assessment in clinical practice.

PMID- 29656262
TI  - Corrigendum to "Post-traumatic stress symptoms are associated with physical
      multimorbidity: Findings from the Adult Psychiatric Morbidity Survey 2007"
      [Journal of Affective Disorders 232 (2018) 385-392].

PMID- 29656263
TI  - Early improvement as a predictor of final remission in major depressive disorder:
      New insights in electroconvulsive therapy.
AB  - BACKGROUND: Early improvement to antidepressant drugs predicts remission, but the
      predictive value of early improvement to electroconvulsive therapy (ECT) is still
      unclear. The main aim of this study was to determine the optimal definition of
      early improvement in the treatment of major depressive disorder (MDD) with ECT,
      by analyzing its value as a predictor of remission. METHODS: A naturalistic study
      was conducted in 87 adult MDD patients treated with acute ECT. ROC curves were
      generated to identify the best time point (week 1 or 2 of treatment) predicted
      remission. Sensibility, specificity, and predictive values were calculated for
      several definitions of early improvement previously proposed in the literature
      (20%, 25%, 30%, and 35%). Complementary, time to remission was analyzed and a
      logistic regression model was performed to further characterize the impact of the
      optimal definition of early improvement on remission while adjusting for other
      clinically relevant variables. RESULTS: A 30% reduction in the HAM-D score after
      2 weeks was identified as the optimal definition of early improvement, with
      acceptable sensitivity (76%), and specificity (67%). Complementary analyses
      provided further support for this definition showing a shorter time to remission
      and a significant effect adjusted for the rest of variables. LIMITATIONS:
      Relatively small sample size, ECT restricted to brief bilateral treatment.
      CONCLUSIONS: Early improvement, defined as a 30% of reduction in the HAM-D21
      score at week 2, is a good predictor of remission in MDD patients treated with
      bilateral ECT, with potential clinical impact. Lack of early improvement could
      indicate a need for further changes in treatment strategies.

PMID- 29656265
TI  - Classification of attempted suicide by cluster analysis: A study of 888 suicide
      attempters presenting to the emergency department.
AB  - BACKGROUND: It is essential to understand the latent structure of the population
      of suicide attempters for effective suicide prevention. The aim of this study was
      to identify subgroups among Korean suicide attempters in terms of the details of
      the suicide attempt. METHODS: A total of 888 people who attempted suicide and
      were subsequently treated in the emergency rooms of 17 medical centers between
      May and November of 2013 were included in the analysis. The variables assessed
      included demographic characteristics, clinical information, and details of the
      suicide attempt assessed by the Suicide Intent Scale (SIS) and Columbia-Suicide
      Severity Rating Scale (C-SSRS). Cluster analysis was performed using the Ward
      method. RESULTS: Of the participants, 85.4% (n = 758) fell into a cluster
      characterized by less planning, low lethality methods, and ambivalence towards
      death ("impulsive"). The other cluster (n = 130) involved a more severe and well
      planned attempt, used highly lethal methods, and took more precautions to avoid
      being interrupted ("planned"). The first cluster was dominated by women, while
      the second cluster was associated more with men, older age, and physical illness.
      LIMITATIONS: We only included participants who visited the emergency department
      after their suicide attempt and had no missing values for SIS or C-SSRS.
      CONCLUSIONS: Cluster analysis extracted two distinct subgroups of Korean suicide
      attempters showing different patterns of suicidal behaviors. Understanding that a
      significant portion of suicide attempts occur impulsively calls for new
      prevention strategies tailored to differing subgroup profiles.

PMID- 29656264
TI  - Prospective predictors of first-onset depressive disorders in adolescent females
      with anxiety disorders.
AB  - BACKGROUND: Anxious youth are at increased risk for later depressive disorders,
      but not all anxious youth develop depression. Sequential comorbidity models
      emphasize shared risk factors and anxiety sequelae, but some anxious youth who
      later develop depression may have risk factors that are relatively specific to
      depression, in addition to a liability to anxiety. We examined several variables
      that appear relatively specific to risk for depression-the personality traits of
      low positive affectivity and high sadness, and an electrophysiological measure of
      blunted response to reward - in predicting first-onset depressive disorders and
      depressive symptoms in clinically anxious adolescent girls. METHODS: A sample of
      114 adolescents with baseline anxiety disorders completed personality and
      psychopathology measures, psychophysiology tasks, and diagnostic interviews.
      Interviews and a measure of depressive symptoms were re-administered over 27
      months. RESULTS: After controlling for baseline depressive symptoms, blunted
      reward sensitivity uniquely predicted first-onset depressive disorders and
      depressive symptoms 27 months later. Post-hoc analyses indicated that blunted
      reward sensitivity only predicted first-onset depressive disorders and depressive
      symptoms in girls with high social anxiety symptoms. LIMITATIONS: Analyses were
      unable to account for concurrent anxiety symptoms and disorders. CONCLUSIONS: The
      depression-specific risk factor, blunted reward sensitivity, may comprise one
      pathway to subsequent depressive disorders and symptoms in anxious youth and
      indicate which anxious youth need intervention to prevent later depression,
      particularly in socially anxious girls.

PMID- 29656266
TI  - Cortical and subcortical changes in patients with premenstrual syndrome.
AB  - BACKGROUND: Premenstrual syndrome (PMS) is characterized by a series of
      emotional, physical and behavioral symptoms. Although PMS is related to
      dysfunctions of the central nervous system, the neuropathological mechanism of
      PMS still has not been clearly established. The aim of this study is to evaluate
      potential differences in both cortical thickness and subcortical volumes in PMS
      patients compared to healthy controls (HCs). METHODS: Twenty PMS patients and
      twenty HCs underwent a structural magnetic resonance imaging scan and clinical
      assessment. Cortical thickness and subcortical volumes were computed using the
      FreeSurfer image analysis suite. Relationships between cortical
      thickness/subcortical volumes and the daily rating of severity of problems (DRSP)
      score were then measured in patients. RESULTS: Compared to HCs, PMS patients
      exhibited reduced cortical thickness in the medial prefrontal cortex (MPFC),
      orbitofrontal cortex (OFC) and insula, and increased subcortical volumes of the
      amygdala, thalamus and pallidum. Furthermore, negative correlations were detected
      between the DRSP and cortical thickness in the anterior cingulate cortex and
      precuneus. LIMITATIONS: The study is limited by a small sample size and narrow
      age range of participants. CONCLUSIONS: Our findings indicate that the abnormal
      morphological changes are mainly implicated in emotional regulation and visceral
      perception in PMS patients. We hope that our study may contribute to a better
      understanding of PMS.

PMID- 29656267
TI  - A naturalistic examination of the perceived effects of cannabis on negative
      affect.
AB  - BACKGROUND: Cannabis is commonly used to alleviate symptoms of negative affect.
      However, a paucity of research has examined the acute effects of cannabis on
      negative affect in everyday life. The current study provides a naturalistic
      account of perceived changes in symptoms of depression, anxiety, and stress as a
      function of dose and concentration of Delta9tetrahydrocannabinol (THC) and
      cannabidiol (CBD). METHOD: Data from the app StrainprintTM (which provides
      medical cannabis users a means of tracking changes in symptoms as a function of
      different doses and chemotypes of cannabis) were analyzed using multilevel
      modeling. In total, 11,953 tracked sessions were analyzed (3,151 for depression,
      5,085 for anxiety, and 3,717 for stress). RESULTS: Medical cannabis users
      perceived a 50% reduction in depression and a 58% reduction in anxiety and stress
      following cannabis use. Two puffs were sufficient to reduce ratings of depression
      and anxiety, while 10+ puffs produced the greatest perceived reductions in
      stress. High CBD (>9.5%)/low THC (<5.5%) cannabis was associated with the largest
      changes in depression ratings, while high CBD (>11%)/high THC (>26.5%) cannabis
      produced the largest perceived changes in stress. No changes in the perceived
      efficacy of cannabis were detected across time. However, baseline symptoms of
      depression (but not anxiety or stress) appeared to be exacerbated across
      time/tracked sessions. LIMITATIONS: The primary limitations are the self-selected
      nature of the sample and the inability to control for expectancy effects.
      CONCLUSIONS: Cannabis reduces perceived symptoms of negative affect in the short
      term, but continued use may exacerbate baseline symptoms of depression over time.

PMID- 29656268
TI  - The development and validation of a short version of the 33-item Hypomania
      Checklist (HCL-33).
AB  - BACKGROUND: The misdiagnosis of bipolar disorder (BD) as major depressive
      disorder (MDD) is common in clinical practice and may result in inappropriate
      treatment. The 33-item Hypomania Checklist (HCL-33) is a newly developed
      screening scale for BD with satisfactory psychometric properties. In this study,
      a short version of the HCL-33 was developed and validated to discriminate between
      BD and MDD. METHOD: All interviews were conducted in a major psychiatric hospital
      in China. The short version of HCL-33 (the HCL-23) was initially developed using
      a sample of 186 patients (MDD = 84, BD-I = 46, BD-II = 56) and its performance
      was tested in a separate sample of 164 patients (MDD = 77, BD-I = 44, BD-II =
      43). RESULTS: The HCL-23 showed high internal consistency (Cronbach's alpha =
      0.906) with two-factorial dimensions. Compared to the HCL-33, the HCL-23
      demonstrated a marginally weaker performance in terms of sensitivity+specificity
      (1.38 vs 1.36 for BD vs MDD, 1.33 vs 1.32 for BD-I vs MDD, and 1.44 vs 1.42 for
      BD-II vs MDD). For discriminating BD, BD-I, and BD-II from MDD, the HCL-23 showed
      better sensitivity (0.82 vs 0.67, 0.77 vs 0.68, and 0.86 vs 0.72, respectively)
      than the HCL-33, while the HCL-33 showed better specificity (0.71 vs 0.55, 0.65
      vs 0.55, and 0.71 vs 0.56, respectively) than the HCL-23. CONCLUSION: Both HCL-33
      and HCl-23 have comparable psychometric properties and screening ability for BD.
      The HCL-23 is an effective screening tool for detecting BD in clinical settings.
      The HCL-23 was developed in China, therefore its psychometric properties need to
      be confirmed in different socio-cultural contexts.

PMID- 29656269
TI  - Task-positive and task-negative networks in major depressive disorder: A combined
      fMRI and EEG study.
AB  - BACKGROUND: The study of intrinsic connectivity networks, i.e., sets of brain
      regions that show a high degree of interconnectedness even in the absence of a
      task, showed that major depressive disorder (MDD) patients demonstrate an
      increased connectivity within the default mode network (DMN), which is active in
      a resting state and is implicated in self-referential processing, and a decreased
      connectivity in task-positive networks (TPNs), which increase their activity in
      attention tasks. Cortical localization of this 'dominance' of the DMN over the
      TPN in MDD patients is not fully understood. Besides, this effect has been
      investigated using fMRI and its electrophysiological underpinning is not known.
      METHOD: In this study, we tested the dominance hypothesis using seed-based
      connectivity analysis of resting-state fMRI and EEG data obtained in 41 MDD
      patients and 23 controls. RESULTS: In MDD patients, as compared to controls,
      insula, pallidum/putamen, amygdala, and left dorso- and ventrolateral prefrontal
      cortex are more strongly connected with DMN than with TPN seeds. In EEG, all
      significant effects were obtained in the delta frequency band. LIMITATIONS: fMRI
      and EEG data were not obtained simultaneously during the same session.
      CONCLUSIONS: In MDD patients, major emotion and attention regulation circuits are
      more strongly connected with DMN than with TPN implying they are more prepared to
      respond to internally generated self-related thoughts than to environmental
      challenges.

PMID- 29656270
TI  - Reduced integrity of the uncinate fasciculus and cingulum in depression: A stem
      by-stem analysis.
AB  - INTRODUCTION: The subgenual cingulate gyrus (Brodmann's Area 25: BA25) is
      hypermetabolic in depression and has been targeted successfully with deep brain
      stimulation. Two of the white matter tracts that play a role in treatment
      response are the uncinate fasciculus (UF) and the cingulum bundle. The UF has
      three prefrontal stems, the most medial of which extends from BA25 (which deals
      with mood regulation) and the most lateral of which extends from the dorso
      lateral prefrontal cortex (concerned with executive function). The cingulum
      bundle has numerous fibers connecting the lobes of the cerebrum, with the longest
      fibers extending from BA25 to the amygdala. We hypothesize that there is reduced
      integrity in the UF, specific to the medial prefrontal stems, as well as in the
      subgenual and amygdaloid fibers of the cingulum bundle. Our secondary hypothesis
      is that these changes are present from the early stages of depression. OBJECTIVE:
      Compare the white matter integrity of stems of the UF and components of the
      cingulum bundle in first-onset depressed, recurrent/chronic depressed, and non
      depressed control subjects. METHODS: Depressed patients (n = 103, first-onset =
      57, chronic = 46) and non-depressed control subjects (n = 74) underwent MRI with
      32-directional DTI sequences. The uncinate fasciculi and cingulum bundles were
      seeded, and the fractional anisotropy (FA) measured in each of the three
      prefrontal stems and the body of the UF, as well as the subgenual, body, and
      amygdaloid fiber components of the cingulum bundle. FA measurements were compared
      between groups using ANOVA testing with post-hoc Tukey analysis. RESULTS: There
      were significant reductions in FA in the subgenual and polar stems of the UF
      bilaterally, as well as the subgenual and amygdaloid fibers of the cingulum
      bundle, in depressed patients compared with controls (p < 0.001). There was no
      significant difference seen in the lateral UF stem or the main body of the
      cingulum. No significant difference was demonstrated in any of the tracts between
      first-onset and chronic depression patients. CONCLUSION: Depressed patients have
      reduced white matter integrity in the subgenual and polar stems of the uncinate
      fasciculi but not the lateral stems, as well as in the subgenual and amygdaloid
      cingulum fibers. These changes are present from the first-onset of the disease.

PMID- 29656271
TI  - Spanish validation of a specific measure to assess work-related problems in
      people with multiple sclerosis: The Multiple Sclerosis Work Difficulties
      Questionnaire (MSWDQ-23).
AB  - INTRODUCTION: Unemployment is a significant problem for people with multiple
      sclerosis (MS). The MS Work Difficulties Questionnaire (MSWDQ-23) is a self
      report tool to assess work-related problems in people with MS across three
      domains: physical, psychological/cognitive, and external barriers. The aim of
      this study was to assess the psychometric properties of the Spanish version of
      the MSWDQ-23. METHODS: A multicentre, non-interventional, cross-sectional study
      in adult patients with relapsing-remitting multiple sclerosis (RRMS) or primary
      progressive (PPMS) multiple sclerosis (McDonald 2010 criteria) was conducted.
      Socio-demographic and clinical characteristics as well as health-related quality
      of life using the 29-item Multiple Sclerosis Impact Scale (MSIS-29) were
      collected. RESULTS: A total of 201 subjects were studied (mean age: 43.9 years,
      60% female, 86% with RRMS). Median Expanded Disability Status Scale (EDSS)
      (score: 2.0 [IQR: 1.0-3.5]). The employment rate was 47.3% (n = 95). The MSWDQ-23
      was feasible (90% response rate), with high internal consistency and test-retest
      reliability (Cronbach's alpha = 0.94 and intraclass correlation coefficient-ICC >
      0.87). MSWDQ-23 scores significantly and positively correlated with EDSS and both
      MSIS-29 physical and psychological subscales scores, showing an adequate
      convergent validity. Regarding construct validity, scores of patients with PPMS
      were higher than those of patients with RRMS, reaching statistically significance
      in MSWDQ-23 physical barriers domain and total scores. CONCLUSION: The Spanish
      version of the MSWDQ-23 shows appropriate feasibility, reliability, and
      discriminative performance as a patient-reported outcome. MSWDQ-23 may be a
      valuable addition to measure the impact of a comprehensive spectrum of
      difficulties experienced by people with MS in the workplace.

PMID- 29656272
TI  - Characterisation of cardiac autonomic function in multiple sclerosis based on
      spontaneous changes of heart rate and blood pressure.
AB  - BACKGROUND: Prevalence of cardiovascular autonomic dysfunction (CAD) in multiple
      sclerosis (MS) varies between studies. Cardiac autonomic function is usually
      assessed by cardiovascular reflex tests. We hypothesized that MS is associated
      with CAD, quantifiable by non-invasive means including quantification of
      baroreceptor sensitivity (BRS) and heart rate variability. METHODS: In this study
      a comprehensive suite of cardiovascular autonomic tests based only on the
      spontaneous changes of heart rate and blood pressure was applied to 23 MS
      patients and age and gender-matched controls. From 5-min continuous non-invasive
      recording of the electrocardiogram and blood pressure, heart-rate, blood
      pressure, and autonomic function variables were calculated. Analysis included
      heart rate variability in the time domain, heart rate and blood pressure
      variability in the frequency domain, and baroreceptor sensitivity in both the
      time and frequency domain. RESULTS: BRS measured by the frequency technique in
      high frequency band was found to be significantly lower in MS (16 +/- 9 ms/mmHg)
      compared to controls (29 +/- 17 ms/mmHg) (p < 0.05). Also mean of BRS modulus in
      MS averaged 15 +/- 8 ms/mmHg which is significantly lower compared to controls
      (25 +/- 15 ms/mmHg) (p < 0.05). Systolic blood pressure variability in the high
      frequency band (0.15-0.5 Hz) was found to be significantly higher in the MS
      compared to controls (5.8 +/- 16.7 mmHg2 vs. 1.3 +/- 0.8 mmHg2) (p < 0.05).
      CONCLUSIONS: The results, using techniques novel to MS investigation, showed
      diminished baroreceptor reflex and impaired sympathetic function using frequency
      domain systolic blood pressure variability analysis.

PMID- 29656273
TI  - The feasibility and concurrent validity of performing the Movement Assessment
      Battery for Children - 2nd Edition via telerehabilitation technology.
AB  - BACKGROUND: In rural and remote communities children with motor difficulties have
      less access to rehabilitation services. Telerehabilitation technology is a
      potential method to overcome barriers restricting access to healthcare in these
      areas. Assessment is necessary to guide clinical reasoning; however it is unclear
      which paediatric assessments can be administered remotely. The Movement
      Assessment Battery for Children - 2nd Edition is commonly used by various health
      professionals to assess motor performance of children. AIMS: The aim of this
      study was to investigate the feasibility and concurrent validity of performing
      the Movement Assessment Battery for Children - 2nd Edition remotely via
      telerehabilitation technology compared to the conventional in-person method.
      METHODS AND PROCEDURES: Fifty-nine children enrolled in a state school (5-11
      years old) volunteered to perform one in-person and one telerehabilitation
      mediated assessment. The order of the method of delivery and the therapist
      performing the assessment were randomized. After both assessments were complete,
      a participant satisfaction questionnaire was completed by each child. OUTCOMES
      AND RESULTS: The Bland-Altman limits of agreement for the total test standard
      score were -3.15 to 3.22 which is smaller than a pre-determined clinically
      acceptable margin based on the smallest detectable change. CONCLUSIONS AND
      IMPLICATIONS: This study establishes the feasibility and concurrent validity of
      the administration of the Movement Assessment Battery for Children - 2nd Edition
      via telerehabilitation technology. Overall, participants perceived their
      experience with telerehabilitation positively.

PMID- 29656274
TI  - Meat quality in relation to swine well-being after transport and during lairage
      at the slaughterhouse.
AB  - Cortisol and corticosterone in saliva were evaluated as pig stress biomarkers,
      using pig genotype (Duroc, L62 or Pietrain) and lairage time in the
      slaughterhouse (0, 2.0, 4.0 or 6.0 h) as controlled variables. Although some pigs
      were found to be carriers of stress susceptibility, all were healthy heterozygous
      individuals. Pre-slaughter transport increased cortisol levels in saliva above
      3.0 MUg/L (medium stress), and 4.0 h of lairage in the slaughterhouse raised them
      above 6.0 MUg/L, whereas corticosterone concentrations exceeded 4 MUg/L, which
      are suggestive of high stress. The highest cortisol levels were detected in the
      Duroc genotype. Other factors such as food deprivation, background noise, the
      presence of a large number of animals waiting to be slaughtered, mixing with
      unfamiliar animals or recent mixing of genders may also influence stress.
      Corticosterone proved a reliable indicator of high stress only. Meat quality from
      the pig breeds studied was not affected by lairage in the slaughterhouse for up
      to 6.0 h.

PMID- 29656276
TI  - Cannabinoid hyperemesis syndrome: A case report.

PMID- 29656275
TI  - Evaluation of decontamination efficacy of commonly used antimicrobial
      interventions for beef carcasses against Shiga toxin-producing Escherichia coli.
AB  - In Argentina, Shiga toxin producing Escherichia coli (STEC) serogroups O157, O26,
      O103, O111, O145 and O121 are adulterant in ground beef. In other countries, the
      zero-tolerance approach to all STEC is implemented for chilled beef. Argentinean
      abattoirs are interested in implementing effective interventions against STEC on
      carcasses. Pre-rigor beef carcasses were used to determine whether nine
      antimicrobial strategies effectively reduced aerobic plate, coliform and E. coli
      counts and stx and eae gene prevalence. These strategies were: citric acid (2%;
      automated), acetic acid (2%; manual and automated), lactic acid (LA 2%; manual
      and automated), LA (3%; automated), electrolytically-generated hypochlorous acid
      (400 ppm; manual), hot water (82  degrees C; automated) and INSPEXX (0.2%;
      automated). Automated application of 2% LA after 30-60-min aeration and 3% LA at
      55  degrees C were the most effective interventions. Automated application was
      more effective than manual application. Decontamination of beef carcasses through
      automated application of lactic acid and hot water would reduce public health
      risks associated with STEC contamination.

PMID- 29656277
TI  - Research challenges in somatoform disorders: A narrative review.

PMID- 29656278
TI  - Anxiety, Depression, and Adverse Clinical Outcomes in Patients With Atrial
      Fibrillation Starting Warfarin: Cardiovascular Research Network WAVE Study.
AB  - BACKGROUND: Anxiety and depression are associated with worse outcomes in several
      cardiovascular conditions, but it is unclear whether they affect outcomes in
      atrial fibrillation (AF). In a large diverse population of adults with AF, we
      evaluated the association of diagnosed anxiety and/or depression with stroke and
      bleeding outcomes. METHODS AND RESULTS: The Cardiovascular Research Network WAVE
      (Community-Based Control and Persistence of Warfarin Therapy and Associated Rates
      and Predictors of Adverse Clinical Events in Atrial Fibrillation and Venous
      Thromboembolism) Study included adults with AF newly starting warfarin between
      2004 and 2007 within 5 health delivery systems in the United States. Diagnosed
      anxiety and depression and other patient characteristics were identified from
      electronic health records. We identified stroke and bleeding outcomes from
      hospitalization databases using validated International Classification of
      Diseases, Ninth Revision (ICD-9), codes. We used multivariable Cox regression to
      assess the relation between anxiety and/or depression with outcomes after
      adjustment for stroke and bleeding risk factors. In 25 570 adults with AF
      initiating warfarin, 490 had an ischemic stroke or intracranial hemorrhage (1.52
      events per 100 person-years). In multivariable analyses, diagnosed anxiety was
      associated with a higher adjusted rate of combined ischemic stroke and
      intracranial hemorrhage (hazard ratio, 1.52; 95% confidence interval, 1.01-2.28).
      Results were not materially changed after additional adjustment for patient-level
      percentage of time in therapeutic anticoagulation range on warfarin (hazard
      ratio, 1.56; 95% confidence interval, 1.03-2.36). In contrast, neither isolated
      depression nor combined depression and anxiety were significantly associated with
      outcomes. CONCLUSIONS: Diagnosed anxiety was independently associated with
      increased risk of combined ischemic stroke and intracranial hemorrhage in adults
      with AF initiating warfarin that was not explained by differences in risk factors
      or achieved anticoagulation quality.

PMID- 29656279
TI  - Drug-Eluting Resorbable Magnesium Scaffold Implantation in ST-Segment Elevation
      Myocardial Infarction: A Pilot Study.
AB  - OBJECTIVES: To assess feasibility and short-term clinical outcomes associated
      with resorbable magnesium scaffold (RMS) implantation in the setting of primary
      percutaneous coronary intervention for ST-segment elevation myocardial infarction
      (STEMI). BACKGROUND: RMS implantation has demonstrated favorable clinical
      outcomes in stable coronary artery disease patients. However, to date, data are
      lacking in the setting of STEMI. METHODS: This is a single-center prospective non
      randomized pilot study. Patients admitted for STEMI were enrolled according to
      prespecified inclusion and exclusion criteria. The primary endpoint was device
      oriented composite endpoint (DOCE), including cardiac death, target-vessel
      myocardial infarction, and target-lesion revascularization (TLR) within 30 days
      of the index procedure. Secondary endpoints were procedural success, any
      probable/definite scaffold thrombosis, and DOCE at subsequent follow-up. RESULTS:
      From December 1, 2016 to October 30, 2017, a total of 18 patients were included.
      Follow-up data were available for 17 patients (94%). There was no primary
      endpoint event. Procedural success was 100%. Patients were followed for a median
      of 153 days (range, 59-326 days). Over that extended follow-up period, 1 case of
      TLR occurred 102 days after the index procedure. There was no case of definite or
      probable scaffold thrombosis. CONCLUSIONS: This pilot study is the first to
      assess feasibility and clinical outcomes associated with RMS implantation in
      selected STEMI patients. The results seem reassuring, with favorable short-term
      clinical outcomes and absence of definite/probable scaffold thrombosis, and
      should prompt further research including randomized controlled trials evaluating
      RMS implantation in the setting of STEMI.

PMID- 29656280
TI  - Real-World Bioresorbable Vascular Scaffold Experience Compared With Second
      Generation Metallic Drug-Eluting Stents in Complex Coronary Lesions.
AB  - OBJECTIVES: The aim of the study was to compare the acute outcomes of Absorb
      bioresorbable vascular scaffolds (BVS) and second-generation drug-eluting stent
      (DES) implantation in routine clinical practice. There is a paucity of data
      regarding BVS use in a real-world patient population. METHODS: The study
      population comprised 40 consecutive patients who underwent percutaneous coronary
      intervention (PCI) with BVS implantation at a tertiary-care center in New York,
      New York between July and December of 2016. An optimal implantation technique
      including adequate lesion preparation, mandatory postdilation, and optical
      coherence tomography (OCT) imaging was used in all cases. De novo lesions treated
      with BVS were compared to lesions treated with DES matched by OCT calcium arc,
      scaffold/stent size, use of atherectomy device, and lesion postdilation. Acute
      lumen gain, minimal device area, malapposition, eccentricity, and symmetry index
      were assessed using OCT. RESULTS: We analyzed OCT images of 40 BVS cases and 40
      matching DES cases from 35 and 40 patients, respectively. Compared to the DES
      group, the BVS group demonstrated similar acute lumen gain, minimal
      scaffold/stent area, eccentricity index, and symmetry index after PCI. There were
      fewer malapposed struts detected after BVS implantation; however, malapposition
      distance and length were not different between the groups. CONCLUSION: BVS
      implantation in a real-world patient population with optimal implantation
      technique resulted in similar stent expansion and better strut apposition
      compared to DES implantation.

PMID- 29656281
TI  - Treatment of Very Small De Novo Coronary Artery Disease With 2.0 mm Drug-Coated
      Balloons Showed 1-Year Clinical Outcome Comparable With 2.0 mm Drug-Eluting
      Stents.
AB  - OBJECTIVE: To evaluate the 1-year clinical outcomes of patients treated with 2.0
      mm drug-coated balloon (DCB) vs 2.0 mm drug-eluting stent (DES) implantation in
      small-caliber vessel de novo coronary artery disease (CAD). METHODS: All patients
      treated with 2.0 mm DCB or 2.0 mm DES for very small vessel de novo CAD from July
      2014 to June 2016 were included in this study. The primary endpoint was the
      occurrence of target-lesion failure (TLF) and time to TLF, defined as a
      combination of cardiac mortality, target-vessel myocardial infarction, and target
      lesion revascularization (TLR). RESULTS: A total of 87 patients (96 lesions) were
      implanted with 2.0 mm DCBs and 200 patients (223 lesions) were implanted with 2.0
      mm DESs during the study period. Mean reference vessel diameter was similar
      between the DCB and DES groups (1.88 +/- 0.38 mm vs 1.95 +/- 0.21 mm,
      respectively; P=.11). The 1-year TLF rates were 7.0% in the DCB group and 8.2% in
      the DES group (P=.73). TLF was driven by TLR in both groups. Bailout stenting was
      performed in 7 patients (8 lesions) who received a DCB. Stent thrombosis was seen
      in 4 patients (2.0%) who underwent DES implantation. There was no vessel
      thrombosis noted in the DCB group. Cardiogenic shock was identified as a direct
      and significant predictor for both the occurrence of TLF and time to TLF.
      CONCLUSIONS: In this first report, treatment of very small vessel CAD with 2.0 mm
      DCB vs 2.0 mm DES was associated with similar 1-year TLF rates.

PMID- 29656282
TI  - Intrapopulation Chromosomal Polymorphism in Mazama gouazoubira (Cetartiodactyla;
      Cervidae): The Emergence of a New Species?
AB  - Mazama gouazoubira is a small deer species widely distributed in South America.
      Previous studies have shown that this species presents intraspecific chromosomal
      polymorphisms, which could affect fertility due to the effects of chromosomal
      rearrangements on gamete formation. Important aspects regarding the karyotype
      evolution of this species and the genus remain undefined due to the lack of
      information concerning the causes of this chromosomal variation. Nineteen
      individuals belonging to the Mazama gouazoubira population located in the
      Pantanal were cytogenetically evaluated. Among the individuals analyzed, 9 had B
      chromosomes and 5 carried a heterozygous centric fusion (2n = 69 and FN = 70). In
      3 individuals, the fusion occurred between chromosomes X and 16, in 1 individual
      between chromosomes 7 and 21, and in another individual between chromosomes 4 and
      16. These striking polymorphisms could be explained by several hypotheses. One is
      that the chromosome rearrangements in this species are recent and not fixed in
      the population yet, and another hypothesis is that they represent a balanced
      polymorphism and that heterozygotes have an adaptive advantage. On the other
      hand, these polymorphisms may negatively influence fertility and raise questions
      about sustainability or reproductive isolation of the population.

PMID- 29656283
TI  - Economic and Political Innovation for Nutritional Improvement.
AB  - Large shares of the world population are still affected by nutrition deficiencies
      and undernutrition. However, the current global agriculture and food system and
      its international governance shows signs of serious malfunctioning, and is not
      equipped to cope with the current and future challenges it is facing. In view of
      the complex and multi-dimensional nature of nutrition problems, a framework is
      put forward here to improve the understanding of underlying causalities, and to
      identify priorities for action. In doing so, this paper focuses on economic and
      policy innovation. Better nutrition policy requires systematic, multi-faceted
      policy innovations, that is, the re-design of the current global food and
      nutrition governance system, and the adoption of innovative economic and
      political approaches. To achieve efficient and effective nutrition policy, more
      attention, leadership, funds, and a global organizational home for better
      coordination are needed. A systematic science and policy interface in the form of
      an International Panel on Food, Nutrition and Agriculture is proposed to provide
      a strong evidence base for nutrition policies.

PMID- 29656284
TI  - Findings of Optical Coherence Tomography Angiography in Best Vitelliform Macular
      Dystrophy.
AB  - PURPOSE: To evaluate the vascular anatomy of eyes with Best vitelliform macular
      dystrophy (BVMD) using optical coherence tomography angiography (OCTA). METHODS:
      This retrospective case-control study enrolled 11 consecutive BVMD patients and
      13 age-matched healthy participants. Both eyes of each participant were imaged
      using a macular OCTA scan (3 * 3 mm) by 70-kHz 840-nm spectral-domain OCT. The
      flow signal was calculated using the split-spectrum amplitude-decorrelation
      angiography (SSADA) algorithm. RESULTS: Qualitative analysis showed uneven hypo-
      and hyperintense signal changes at the choriocapillary level in OCTA images of
      BVMD patients. Quantitative analysis showed significant reductions in the flow
      density of the superficial vascular layer (whole: 49.2% vs. 53.9%, p < 0.001) and
      the choriocapillary flow area (5.1 vs. 5.5 mm2, p = 0.02) in BVMD patients
      compared to controls. The choriocapillary flow area in the postvitelliform group
      was reduced compared to that of the vitelliform group. There was a statistically
      significant association between choriocapillary flow area and superficial
      vascular flow density (p = 0.045), choriocapillary flow area and foveal avascular
      zone area (p = 0.03). CONCLUSIONS: Vascular changes in BVMD were apparent in the
      choriocapillary layer. The changes became more striking in late stages of the
      disease. OCTA provides useful quantitative measurements for staging and
      monitoring the progression of BVMD.

PMID- 29656285
TI  - Sociocultural and Familial Factors Associated with Weight Bias Internalization.
AB  - BACKGROUND/AIMS: Sociocultural and familial factors associated with weight bias
      internalization (WBI) are currently unknown. The present study explored the
      relationship between interpersonal sources of weight stigma, family weight
      history, and WBI. METHODS: Participants with obesity (N = 178, 87.6% female,
      71.3% black) completed questionnaires that assessed the frequency with which they
      experienced weight stigma from various interpersonal sources. Participants also
      reported the weight status of their family members and completed measures of WBI,
      depression, and demographics. Participant height and weight were measured to
      calculate body mass index (BMI). RESULTS: Linear regression results (controlling
      for demographics, BMI, and depression) showed that stigmatizing experiences from
      family and work predicted greater WBI. Experiencing weight stigma at work was
      associated with WBI above and beyond the effects of other sources of stigma.
      Participants who reported higher BMIs for their mothers had lower levels of WBI.
      CONCLUSION: Experiencing weight stigma from family and at work may heighten WBI,
      while having a mother with a higher BMI may be a protective factor against WBI.
      Prospective research is needed to understand WBI's developmental course and
      identify mechanisms that increase or mitigate its risk.

PMID- 29656286
TI  - Classification of Uniparental Isodisomy Patterns That Cause Autosomal Recessive
      Disorders: Proposed Mechanisms of Different Proportions and Parental Origin in
      Each Pattern.
AB  - Patients with autosomal recessive (AR) disorders are usually born to parents both
      of whom are heterozygous carriers of the disease. However, in some instances only
      one of the parents is a carrier and a mutation is segregated to the patient
      through uniparental isodisomy (UPiD). Recently, an increasing number of such case
      reports has been published, and it has become clear that there are several
      different UPiD patterns that cause AR disorders. In this article, we report 3
      remarkable patients with different patterns of UPiD. We then review 85 cases
      collected in the literature. We realized that they can be classified into 3
      patterns: UPiD of the whole chromosome, segmental UPiD with uniparental
      heterodisomy (UPhD), and segmental UPiD caused by post-zygotic mitotic
      recombination (MiRe). Whole chromosomal UPiD accounted for the majority of cases,
      with paternal origin accounting for approximately twice as many cases as maternal
      origin. Most cases of segmental UPiD with UPhD were of maternal origin, with a
      dominancy of nondisjunction in meiosis I, while segmental UPiD through MiRe is
      the smallest pattern with equal parental origin. These differences in proportion
      and parental origin in each pattern can be explained by considering
      nondisjunction during oogenesis as the starting point and UPiD as subsequent
      events.

PMID- 29656287
TI  - Respiratory Management of Extremely Preterm Infants: An International Survey.
AB  - BACKGROUND: There are significant international variations in chronic lung
      disease rates among very preterm infants yet there is little data on
      international variations in respiratory strategies. OBJECTIVE: To evaluate
      practice variations in the respiratory management of extremely preterm infants
      born at < 29 weeks' gestational age (GA) among 10 neonatal networks participating
      in the International Network for Evaluating Outcomes (iNeo) of Neonates
      collaboration. METHODS: A web-based survey was sent to the representatives of 390
      neonatal intensive care units from Australia/New Zealand, Canada, Finland,
      Illinois (USA), Israel, Japan, Spain, Sweden, Switzerland, and Tuscany (Italy).
      Responses were based on practices in 2015. RESULTS: Overall, 321 of the 390 units
      responded (82%). The majority of units within networks (40-92%) mechanically
      ventilate infants born at 23-24 weeks' GA on continuous positive airway pressure
      (CPAP) with 30-39% oxygen in respiratory distress within 48 h after birth, but
      the proportion of units that offer mechanical ventilation for infants born at 25
      26 weeks' GA at similar settings varied significantly (20-85% of units within
      networks). The most common respiratory strategy for infants born at 27-28 weeks'
      GA on CPAP with 30-39% oxygen with respiratory distress within 48 h after birth
      used by units also varied significantly among networks: mechanical ventilation (0
      60%), CPAP (3-82%), intubation and surfactant administration with immediate
      extubation (0-75%), and less invasive surfactant administration (0-68%).
      CONCLUSIONS: There are marked variations but also similarities in respiratory
      management of extremely preterm infants between networks. Further collaboration
      and exploration is needed to better understand the association of these
      variations in practice with pulmonary outcomes.

PMID- 29656288
TI  - Progress in Interventional Pulmonology.

PMID- 29656289
TI  - High Concentration of Glial Cell Line-Derived Neurotrophic Factor Protects
      Primary Astrocytes from Apoptosis.
AB  - BACKGROUND: Studies have shown that astrocytes play an important role in a
      variety of biological processes, so damage to astrocytes can cause a series of
      related diseases. Glial cell line-derived neurotrophic factor (GDNF) has always
      been considered a protective factor for dopamine neurons. However, it remains
      unclear whether GDNF has a protective effect on glial cells, especially
      astrocytes. In this study, we put forward the hypothesis that a high
      concentration of GDNF in the microenvironment of astrocytes exerts an inhibitory
      effect on the apoptosis of astrocytes by DNA-damaging reagents. METHODS: We
      isolated, purified, and identified primary astrocytes from neonate rats.
      Astrocytes were exposed to mitoxantrone (MTN, a DNA-damaging compound) for 24 h.
      The effects of MTN on astrocytes were tested by Hoechst 33342 staining, CCK-8
      assay, and flow cytometry assay. One of the concentrations of MTN was applied to
      construct an apoptotic model of astrocytes. The astrocytes were then treated with
      GDNF together with a selected concentration of MTN for 24 h. The cell viability,
      cell nucleus morphology, and apoptosis ratio of the cells was assessed by Hoechst
      33342 staining, CCK-8 assay, and flow cytometry assay, respectively. RNA
      sequencing (RNA-Seq), quantitative PCR analysis, and KEGG pathway mapping were
      performed to examine the genes involved in the procedure. Finally, Western blot
      analysis was applied to confirm the expression levels of the proteins of
      interest. RESULTS: Hoechst 33342 staining revealed a one-tenth change in the
      percentage of Hoechst-positive cells after the addition of 500 ng/mL GDNF
      combined with 1,000 nM MTN for 24 h. The viability of the cells treated the same
      as described above was 1.4-fold that of the control group. Flow cytometry assays
      indicated that the apoptotic rates were 17.67, 8.67, and 4.34% for 0, 200, and
      500 ng/mL GDNF, respectively. Birc2, Birc3, and Gadd45b were linked to the
      antiapoptotic process induced by GDNF in astrocytes. Western blot analysis
      confirmed the elevated expression of Birc2 and Gadd45b. CONCLUSIONS: Our studies
      revealed that GDNF has a noticeable antiapoptotic effect on gene-injured
      astrocytes. This may provide critical clues for the treatment of a series of
      diseases in which damaged astrocytes are involved.

PMID- 29656290
TI  - Psychosocial, Cognitive, and Physical Impact of Elaborate Consultations and Life
      Review in Female Patients with Non-Metastasized Breast Cancer.
AB  - BACKGROUND: Elaborate consultations and life review (ECLR) has been regularly
      applied in patients of various cancer entities and stages within Anthroposophic
      integrative oncology concepts. However, a lack of systematic research in this
      field has been detected. To close this gap of knowledge, we evaluated the impact
      of ECLR in patients with non-metastasized breast cancer before, during, and after
      primary oncological treatment. METHODS: Patient-reported outcome measures were
      evaluated by analyzing European Organisation for Research and Treatment of Cancer
      Quality of Life Questionnaires (EORTC QLQ-C30) in patients with non-metastasized
      breast cancer who had received either oncological standard therapy alone or in
      combination with ECLR. RESULTS: 95 female patients were eligible for
      questionnaire analysis (median age 58 years). Adjusted multivariable linear
      regression analysis revealed that ECLR was associated with significant
      improvements in medium-term global health/quality of life and emotional, social,
      and cognitive functioning. Furthermore, ECLR was associated with significant
      reductions of short-term appetite loss burden, pain, and short- and medium-term
      financial difficulties. Subgroup analyses revealed significant improvements in
      pivotal quality-of-life aspects including fatigue (p = 0.002) in chemotherapy
      treated patients after ECLR. CONCLUSIONS: 12 months of surveillance of breast
      cancer patients reveals medium-term recovery of the global health status/quality
      of life and cognitive and psychosocial well-being associated with ECLR. In
      addition, our data indicate a possible association between ECLR and reduced short
      term fatigue burden, which has to be re-confirmed prospectively in a larger study
      cohort. As long-term cancer survivors develop psychological symptoms similar to
      patients with chronic diseases, prospective studies should evaluate the impact of
      ECLR on the psychosocial well-being in these patients.

PMID- 29656291
TI  - Activin-A Is a Pro-Inflammatory Regulator in Type-2-Driven Upper Airway Disease.
AB  - BACKGROUND: Allergic upper airway disease involves pro-inflammatory type-2
      cytokines such as IL-5 and regulatory tissue repair mediators, in particular
      transforming growth factor (TGF)-beta1. The TGF-beta-superfamily member activin-A
      displays multiple biological functions and shares certain signalling pathways
      with TGF-beta1. We aimed to examine the coregulation of mucosal activin-A and TGF
      beta1 in acute allergic and chronic Th2-driven upper airway disease. METHODS: We
      investigated mucosal cytokine expression profiles and kinetics using RT-PCR after
      nasal allergen challenges in patients with seasonal allergic rhinitis.
      Furthermore, we analysed mucosal specimens from patients with chronic upper
      airway disease with nasal polyps using ELISPOTs and confocal microscopy. In
      addition, we stimulated nasal mucosa ex vivo from patients with nasal polyps as
      well as primary nasal cell cultures from healthy donors. RESULTS: Mucosal activin
      A expression revealed increasing correlation with IL-5 and TGF-beta1 at 0.25, 6,
      and 24 h, respectively, and was significantly upregulated at 6 h after allergen
      challenge. The correlated expression was found to be more pronounced in chronic
      disease with nasal polyps, showing substantially (48-fold) increased activin-A
      producing cells in nasal polyps by ELISPOT, while submucosal downstream
      signalling as determined by confocal microscopy was decreased. Ex vivo
      stimulations of nasal tissue suggested that activin-A and TGF-beta1 mutually
      regulate each other's expression at the mRNA level and, when combined, enhance IL
      5 expression. CONCLUSION: Activin-A in allergic upper airway disease acts as a
      pro-inflammatory mediator and TGF-beta1 modifier. Our data in the upper airways
      oppose the view of potentially anti-inflammatory properties in contrast to
      lymphatic compartments.

PMID- 29656292
TI  - C-Reactive Protein and Procalcitonin in Case Reports of Drug Reaction with
      Eosinophilia and Systemic Symptoms (DRESS) Syndrome.
AB  - BACKGROUND: The spectrum of inflammatory marker response in DRESS (drug reaction
      with eosinophilia and systemic symptoms) syndrome has not been systematically
      characterized. METHODS: An epidemiological biomarker study of C-reactive protein
      (CRP) and procalcitonin (PCT) values in patients with DRESS syndrome reported at
      2 regional pharmacovigilance centers in Switzerland or published in the medical
      literature 2008-2016 was performed. RESULTS: Ninety-four DRESS cases were
      studied. All cases showed a CRP value > 10 mg/L (the upper limit of normal). The
      mean CRP value was 109.2 +/- 79.4 mg/L. CRP values were significantly higher in
      22 cases where a cause of inflammation besides DRESS could not be excluded (mean
      162.1 vs. 92.9 mg/L; p = 0.003). Receiver operator characteristics curve analysis
      showed a moderate performance with a CRP cut-off value of 99.4 mg/L (AUC 0.717)
      to distinguish between patients with and without a possible additional cause of
      inflammation. The mean and median PCT values were 2.44 +/- 5.94 and 0.69 ng/mL,
      respectively (n = 25 patients). Patients in whom an additional cause of
      inflammation besides DRESS could not be excluded showed a median PCT of 1.37
      ng/mL (n = 9) versus 0.67 ng/mL (n = 16) in patients with DRESS only. PCT values
      were above the normal cut-off of 0.1 ng/mL, suggestive of bacterial infection in
      all but 1 case. Furthermore, there was a correlation between PCT values and
      hepatic enzyme measurements. CONCLUSIONS: Evaluating CRP and PCT values might be
      of use in helping physicians to distinguish between cases of DRESS syndrome with
      and without concurrent infection or other causes of inflammation. Further
      prospective investigation is required to define the use of these inflammatory
      markers in the management of DRESS.

PMID- 29656293
TI  - What Does it Need to Improve Nutrition Quality? The Role of Public Partners.
AB  - Public partners play a key role when we want to improve nutrition quality. They
      will not succeed, when they try to achieve the goal alone or tend to dominate
      other players. In their responsibility for common interests it is up to public
      partners to moderate and facilitate the multi-stakeholder and multi-sectorial
      dialogue to improve nutrition quality. It is up to public partners to establish
      clear legal and structural guidelines aiming to bring all partners together, to
      avoid conflicts of interests and, above all, establish conditions, in which
      consumers are sufficiently informed about food and nutrition, so that they are
      motivated, empowered, and adequately protected to take their own responsible
      decisions.

PMID- 29656294
TI  - Gray Matter Heterotopia, Mental Retardation, Developmental Delay, Microcephaly,
      and Facial Dysmorphisms in a Boy with Ring Chromosome 6: A 10-Year Follow-Up and
      Literature Review.
AB  - Ring chromosome 6, r(6), is an extremely rare cytogenetic abnormality with
      clinical heterogeneity which arises typically de novo. The phenotypes of r(6) can
      be highly variable, ranging from almost normal to severe malformations and
      neurological defects. Up to now, only 33 cases have been reported in the
      literature. In this 10-year follow-up study, we report a case presenting
      distinctive facial features, severe developmental delay, and gray matter
      heterotopia with r(6) and terminal deletions of 6p25.3 (115426-384174, 268 kb)
      and 6q26-27 (168697778-170732033, 2.03 Mb) encompassing 2 and 15 candidate genes,
      respectively, which were detected using G-banding karyotyping, FISH, and
      chromosomal microarray analysis. We also analyzed the available information on
      the clinical features of the reported r(6) cases in order to provide more
      valuable information on genotype-phenotype correlations. To the best of our
      knowledge, this is the first report of gray matter heterotopia manifested in a
      patient with r(6) in China, and the deletions of 6p and 6q in our case are the
      smallest with the precise size of euchromatic material loss currently known.

PMID- 29656295
TI  - From Complementary to Integrative Medicine and Health: Do We Need a Change in
      Nomenclature?

PMID- 29656296
TI  - Impact of Pathological Fractures on the Prognosis of Primary Malignant Bone
      Sarcoma in Children and Adults: A Single-Center Retrospective Study of 205
      Patients.
AB  - BACKGROUND: The purpose of this study was to investigate whether pathological
      fractures (PF) influence the prognosis of patients with osteosarcoma (OS) or
      Ewing tumor (ET) regarding 5-year survival, occurrence of metastases, and local
      recurrence. METHODS: We retrospectively analyzed 205 patients with metastatic and
      nonmetastatic OS or ET. Survival analysis was performed for all patients and
      differentiated for patients with OS (n = 127) and ET (n = 78) as well as for
      adults (n = 101) and children (n = 104). RESULTS: Patients with PF showed
      survival rates of 64% compared to 83% for those without PF (p = 0.023). Local
      recurrence occurred in 7% of the patients without and in 24% of those with PF (p
      = 0.023). In patients with ET and in children, survival analysis showed no
      significant difference between patients with and without PF in survival and local
      recurrence rates. In patients with OS, survival rate decreased from 83 to 59% (p
      = 0.024) and local recurrence rate increased from 13 to 30% (p = 0.042). In
      adults, survival rate decreased from 78 to 51% (p = 0.004) and local recurrence
      rate increased from 13 to 42% (p < 0.001). In multivariate analysis, age and PF
      were associated with inferior survival. CONCLUSION: This study suggests that the
      occurrence of PF has a negative impact on survival and implicates an increased
      risk of local recurrence. In children and in patients with ET, PF did not have a
      prognostic impact.

PMID- 29656297
TI  - Reducing Mineral and Vitamin Deficiencies through Biofortification: Progress
      Under HarvestPlus.
AB  - Fundamentally, the prevalence of mineral and vitamin deficiencies is high in
      developing countries due to the fact that agricultural systems do not produce
      sufficient foods rich in minerals and vitamins. Biofortification involves
      breeding staple food crops to increase their micronutrient content, targeting
      staple foods widely consumed by low-income families globally. In so doing,
      biofortification contributes to solving the underlying problem of mineral and
      vitamin deficiencies by increasing the amount of iron, zinc, and provitamin A
      produced by food systems. When HarvestPlus first started in 2003, there was much
      doubt among a range of stakeholders, that biofortification would work. First, we
      had to prove to the plant science community that higher target levels iron, zinc,
      and provitamin A could be bred into high-yielding, profitable varieties.
      Presently, over 150 varieties of 12 biofortified crops have passed the agronomic
      tests of varietal release committees in 30 developing countries. In 3-5 years,
      biofortified varieties will be available to farmers and consumers in an
      additional 25 countries. The nutrition community initially questioned the
      efficacy of biofortified crops - would the levels of retained nutrients and
      absorption be high enough? HarvestPlus has commissioned 15 efficacy trials, all
      undertaken in developing countries. While 5 of these studies are still in
      process, there is already sufficient positive published evidence for iron and
      provitamin A. Can adoption of biofortified crops by farmers be scaled up, and a
      public health impact demonstrated? HarvestPlus estimates that 20 million farmers
      and consumers presently grow and consume biofortified crops in 8 target
      countries. The final and major challenge is to mainstream biofortification into
      the fabric of "business-as-usual" of a range of organizations - public and
      private agricultural research, institutions that focus on bringing improved
      agricultural technologies to farmers including multi-lateral lending
      institutions, private companies, non-governmental organizations, and the policies
      and programs of national governments, regional organizations, and UN agencies.

PMID- 29656299
TI  - Effects of Moisture Content and Loading Profile on Changing Properties of Bone
      Micro-Biomechanical Characteristics.
AB  - BACKGROUND Our study explored the influences of hydration conditions and loading
      methods on the mechanical properties of cortical bones and cancellous bones.
      MATERIAL AND METHODS Elastic modulus and hardness of human cortical bones and
      cancellous bones that contained different moisture levels (20%, 30%, 40%, 50%,
      and 60%) were measured with nanoindentation with different peak loads and loading
      rates. Cortical bones with 20% and 60% moisture were tested with 30 nm, 40 nm,
      and 50 nm peak loads at 6 nm/s, 8 nm/s, and 10 nm/s loading rates, respectively.
      Cancellous bones with 5% or 40% moisture percentages were tested with 600 MUN,
      750 MUN, and 1000 MUN peak loads at 200 MUN/s, 250 MUN/s, and 333 MUN/s loading
      rates, respectively. RESULTS Under the same loading condition, specimens with
      higher moisture contents showed decreased elastic modulus and hardness. Under
      different loading conditions, the loading modes had little influence on elastic
      modulus and hardness of cortical bone and cancellous bone with low moisture, but
      had significant influence on specimens with higher moistures. CONCLUSIONS The
      elastic modulus and bone hardness were affected by the moisture content and the
      loading conditions in cortical and cancellous bones with high hydration condition
      but not in those with low hydration condition.

PMID- 29656298
TI  - High Expression of Peroxiredoxin 1 Is Associated with Epithelial-Mesenchymal
      Transition Marker and Poor Prognosis in Gastric Cancer.
AB  - BACKGROUND Recent studies show that peroxiredoxin 1 (Prdx1) contributes to the
      progression and poor prognosis of carcinoma through multiple mechanisms. However,
      there is little information on its expression and prognostic value in gastric
      cancer. This study investigated the expression of Prdx1 in gastric cancer, along
      with evaluating its clinical-pathological and prognostic importance. MATERIAL AND
      METHODS A total of 189 pairs of gastric cancer and paracarcinomatous tissues were
      assessed for Prdx1 expression and its association with clinical characteristics.
      The molecular mechanism was further investigated through in vitro
      experimentation. RESULTS The mRNA and protein levels of Prdx1 in the GC tissues
      were higher than in the peri-tumor tissues. We also found that high Prdx1
      expression was positively correlated with the lymph node invasion and poor
      prognosis. It also served as an autonomous prognostic factor for patients with
      gastric cancer. Moreover, Prdx1 regulates the invasion and metastasis of GC cell
      lines through inhibiting E-Ca expression. CONCLUSIONS Prdx1 can promote
      epithelial-mesenchymal transition and gastric cancer progression. Therefore, it
      might be a therapeutic target and prognostic indicator for gastric cancer
      patients.

PMID- 29656300
TI  - The Sineoculis Homeobox Homolog 1 (SIX1) Gene Regulates Paclitaxel Resistance by
      Affecting Reactive Oxygen Species and Autophagy in Human Hepatocellular Carcinoma
      Cell Line HepG2.
AB  - BACKGROUND The objective of this study was to explore the role of SIX1 in
      paclitaxel (TAX) resistance of HepG2 cells via reactive oxygen species (ROS) and
      autophagy pathway. MATERIAL AND METHODS Hepatoma cell line HepG2 was treated with
      SIX1 knockdown or/and TAX. Cell growth was detected by MTT assay and colony
      formation assay. Cell apoptosis was evaluated with flow cytometry. ROS levels
      were detected using flow cytometry (stained with DCFH2-DA). Western blot was
      conducted to detect the expression of SIX1 and autophagy-related proteins.
      RESULTS TAX suppressed the proliferation of HepG2 cells in a time/dose-dependent
      manner, and upregulated the expression of SIX1. SIX1 siRNA increased TAX
      sensitivity of HepG2 cells and upregulated cell ROS levels. SIX1 siRNA combined
      with TAX treatment activated autophagy of HepG2 cells. N-acetyl-L-cysteine (NAC)
      partially attenuated SIX1 siRNA-induced ROS level increases, and autophagy
      inhibitor 3-MA notably enhanced SIX1 siRNA-induced cell apoptosis. CONCLUSIONS
      Knockdown of SIX1 increased cell ROS levels and autophagy, promoted cell
      apoptosis, and enhanced TAX sensitivity of HepG2 cells.

PMID- 29656301
TI  - Septoplasty for nasal obstruction due to a deviated nasal septum in adults: a
      systematic review.
AB  - BACKGROUND: The status of current evidence for the effectiveness of septoplasty
      is unclear. This systematic review evaluates the effectiveness of a) septoplasty
      (with or without concurrent turbinate surgery) versus non-surgical management,
      and b) septoplasty with concurrent turbinate surgery versus septoplasty alone,
      for nasal obstruction due to a deviated nasal septum in adults. METHODOLOGY:
      Eligible for inclusion were randomised controlled trials and non-randomised
      designs comparing treatment strategies. Risk of bias was assessed using
      Cochrane's tool. Standardised mean differences and risk differences with 95%
      confidence intervals were calculated. Substantial heterogeneity between included
      studies did not allow meta-analyses. RESULTS: No studies were found comparing
      septoplasty (with or without concurrent turbinate surgery) to non-surgical
      management, but 11 articles were included to compare septoplasty with concurrent
      turbinate surgery to septoplasty alone. Five studies described both subjective
      and objective outcomes; six studies reported one or the other. Risk of bias was
      overall high. Although outcomes generally improved after treatment, eight out of
      nine studies on subjective measures and five out of seven studies on objective
      measures found no additional benefit of turbinate surgery. CONCLUSIONS: Despite
      the routine application of septoplasty in clinical practice, the current body of
      evidence does not support firm conclusions on its effectiveness.

PMID- 29656302
TI  - Anterior laxity of the knee assessed with gravity stress radiograph.
AB  - OBJECTIVE: To clarify the advantage of prone position over supine position in
      radiographically-demonstrating anterior knee laxity measurement for anterior
      cruciate ligament (ACL) injury, and to optimize the radiographic technique for
      the ACL-deficient knees in a clinical setting. MATERIALS AND METHODS: Thirty-nine
      patients with unilateral ACL injury had consented to participate in this study.
      They were divided into two groups and subjected to the different radiographic
      evaluations: study 1 (20 patients); supine versus prone position with knee full
      extended, and study 2 (19 patients); comparison of (1) prone position with knee
      full-extended (FPV), (2) prone position with knee flexed at 15 degrees  (AGV),
      and (3) supine position with calf put on a board at 15 degrees  of knee flexion
      (SGV). Lateral radiographs for both knees were taken and were measured the side
      to-side difference of tibial position related to femur. RESULTS: In study 1, the
      side-to-side difference was 2.8 +/- 1.0 mm in supine position and 4.3 +/- 2.1 mm
      in prone position, showing a statistically significant difference. In study 2,
      the side-to-side difference was 3.7 +/- 2.4 mm in FPV, 4.6 +/- 2.0 mm in AGV, and
      4.2 +/- 2.8 mm in SGV, while the difference in the latter two positions was
      larger than that in FPV. CONCLUSIONS: The anterior laxity in prone position is
      larger than that in supine position for ACL injury. Moreover, the gravity
      assisted lateral radiograph in prone position with knee flexed at 15 degrees 
      could be one of the preferable radiographic techniques and could provide more
      information than the simple radiograph.

PMID- 29656303
TI  - Spondylodiscitis following endovascular abdominal aortic aneurysm repair: imaging
      perspectives from a single centre's experience.
AB  - OBJECTIVE: Very few reports have previously described spondylodiscitis as a
      potential complication of endovascular aortic aneurysm repair (EVAR). We present
      to our knowledge the first case series of spondylodiscitis following EVAR based
      on our institution's experience over an 11-year period. Particular attention is
      paid to the key imaging features and challenges encountered when performing
      spinal imaging in this complex patient group. MATERIALS AND METHODS: Of 1,847
      patients who underwent EVAR at our institution between January 2006 and January
      2017, a total of 9 patients were identified with imaging features of
      spondylodiscitis (0.5%). All cross-sectional studies before and after EVAR were
      assessed by a Consultant Musculoskeletal Radiologist and a Musculoskeletal
      Radiology Fellow to evaluate for features of spondylodiscitis. RESULTS: All 9
      patients had single-level spondylodiscitis involving lumbosacral levels adjacent
      to the aortic/iliac stent graft. Eight out of nine patients had an extensive
      anterior paravertebral phlegmon/abscess that was contiguous with the infected
      stent graft and native aneurysm sac +/- anterior vertebral body erosion. Epidural
      disease was present in only 3 out of 9 patients and was a minor feature. MRI was
      non-diagnostic in 3 out of 9 patients owing to susceptibility artefact. 18F-FDG
      PET/CT accurately depicted the spinal level involved and adjacent paravertebral
      disease in patients with non-diagnostic MRI and was adopted as the follow-up
      modality in 3 out of 5 surviving patients. CONCLUSION: Spondylodiscitis is a rare
      complication post-EVAR. Imaging features of disproportionate anterior
      paravertebral disease and anterior vertebral body bony involvement suggest direct
      spread of infection posteriorly to the adjacent vertebral column. Use of MRI
      versus 18F-FDG PET/CT as the optimal imaging modality should be directed by the
      type of stent graft deployed.

PMID- 29656305
TI  - Do reductions in out-of-pocket expenses for dual energy X-ray absorptiometry
      scans translate to reduced fracture incidence amongst older Australians? A
      population-based study.
AB  - : This study aimed to compare fracture incidence in the elderly pre- and post
      revision of bone density scan reimbursement guidelines, which changed in 2007.
      Fracture incidence by age group was calculated using population-specific data.
      Guideline changes did not appear to reduce fracture incidence in the study region
      located in south-eastern Australia. PURPOSE: In 2007, Medicare Australia revised
      reimbursement guidelines whereby individuals aged 70 years and over received
      reduced out-of-pocket expenses for dual energy X-ray absorptiometry (DXA) scans.
      The current study aims to determine whether fracture incidence in the elderly has
      changed since the revision of reimbursement guidelines. METHOD: Keyword searches
      of the two major radiological centres servicing the Barwon Statistical Division
      (BSD) were used to identify incident fractures for residents aged 75 years and
      over for 2006 and 2012. Pathological fractures were excluded. Fracture incidence
      by age strata (75-79 years, 80-84 years and 85+ years) were calculated using
      population-specific data from the Australian Bureau of Statistics (2006 and
      2012). Standardised fracture ratios were calculated for men and women. RESULTS:
      In total, 996 fracture events were identified for BSD residents during 2006 and
      1260 identified in 2012. The standardised fracture ratios between 2006 and 2012
      were 1.12 (95%CI 1.11, 1.25) for men and 1.08 (95%CI 1.11, 1.16) for women.
      CONCLUSION: The change in reimbursement guidelines appears to have had little
      impact on reducing fracture incidence during this time frame for elderly men and
      women, in fact, fracture rates increased. Future research should investigate
      osteoporosis management following DXA over a longer time frame.

PMID- 29656304
TI  - The gentamicin-collagen implant and the risk of distant metastases of rectal
      cancer following short-course radiotherapy and curative resection: the long-term
      outcomes of a randomized study.
AB  - PURPOSE: A previous randomized study conducted by our group showed that
      application of gentamicin-collagen implant (GCI) into the pelvic cavity after
      total mesorectal excision (TME) reduced the incidence of distant metastases.
      Therefore, we decided to conduct a confirmatory study. METHODS: Patients with
      rectal cancer were included in the study if they met the following criteria:
      adenocarcinoma of the rectum, preoperative short-term radiotherapy (5 * 5 Gy),
      and WHO performance score 0-1. RESULTS: One hundred seventy-six patients were
      randomly assigned either to an experimental group in which GCI was applied (n =
      81) or to a control group without GCI (n = 81). Median follow-up was 80 months.
      Cumulative incidence of distant metastases at 5 years was higher in the control
      group compared to the experimental group: 23.5 vs 8.6% (HR 2.4 [95% CI 1.1-5.5],
      P = 0.005). Overall survival (OS), disease-free survival (DFS), and cancer
      specific survival (CSS) did not differ between the experimental group and the
      control group: HR 0.95 [95% CI 0.55-1.70], P = 0.864; HR 0.85 [95% CI 0.50-1.45],
      P = 0.548, and HR 0.5 [95%CI 0.22-1.22], P = 0.093, respectively. The predefined
      by the protocol subgroup analysis for yp stage III disease showed better DFS in
      the experimental group compared to the control group; HR 0.47 [95%CI 0.23-0.97],
      P = 0.042). CONCLUSIONS: The results confirmed our previous finding that GCI
      applied in the pelvis significantly reduced the rate of distant metastases in
      patients after radical rectal cancer resection.

PMID- 29656306
TI  - Oral and Sublingual Immunotherapy for Treatment of IgE-Mediated Food Allergy.
AB  - Development of active therapies for IgE-mediated food allergy is a critical
      action step toward alleviating the adverse medical, psychosocial, and economic
      burdens on affected patients and families. Significant progress has been observed
      specifically in the application of single-allergen oral and sublingual
      immunotherapy for treatment of IgE-mediated food allergy, with emphasis on milk,
      egg, and peanut as the primary allergens. Oral immunotherapy (OIT) has
      demonstrated efficacy in promoting immunomodulatory effects that lead to the
      clinical outcome of desensitization, defined as reduced reactivity while on
      active OIT, in the majority of treated individuals; however, achievement of
      sustained unresponsiveness following cessation of therapy has been observed in a
      smaller subset of treated subjects. The potential therapeutic benefits of OIT
      must be carefully considered in light of the significant potential for adverse
      events ranging from self-limited or easily treated oropharyngeal, respiratory or
      gastrointestinal symptoms, to persistent abdominal complaints that lead to
      cessation of therapy in an estimated 10-15% of treated individuals. To date, the
      majority of studies have focused on single-allergen OIT approaches; however,
      multi-allergen OIT has shown promise in initial trials and is the subject of
      ongoing investigation to address the complex needs of multi-food allergic
      individuals. Sublingual immunotherapy (SLIT) has been utilized for the treatment
      of food allergy and pollen-food allergy syndrome, demonstrating moderate
      efficacy, a favorable safety profile and variable tolerability, with
      oropharyngeal symptoms most commonly observed. Although studies directly
      comparing OIT and SLIT are limited, in general, the favorable safety profile
      associated with SLIT comes at the expense of reduced efficacy, while the more
      robust clinical effects observed with OIT come at the risk of potentially
      intolerable, treatment-limiting side effects. Future investigation to address
      specific knowledge gaps including optimal dose, duration, age of initiation,
      maintenance schedule, mechanisms, predictors of risk and therapeutic response
      will be important to maximize efficacy, minimize risk and develop personalized,
      effective approaches to targeting food allergy.

PMID- 29656307
TI  - Alveolar Bone Protective Effect of Hiziki Extracts on the Progression of
      Periodontitis.
AB  - The purpose of this study was to evaluate the effects of hiziki extract on
      alveolar bone loss, inflammation, and osteo-biomarker expression in hPDL cells
      (10, 50, 100 MUg/ml final concentrations in culture medium) and on a ligature
      induced periodontitis rat model (50, 100, 200 mg/kg with oral administration).
      Hiziki extract increased alkaline phosphatase activity and mineralized nodule
      formation in hPDL cell. In western blot analysis, hiziki extract resulted in
      increased expression of osteoblast markers, including transforming growth factor
      beta (TGF-beta), SMAD anchor for receptor activation (SARA) and runt-related
      transcription factor 2 (RUNX2) in hDPL cells. Additionally, expression of
      osteoclast markers and inflammatory cytokines was inhibited, which were receptor
      activator of NF-kappaB (RANK), RANK receptor (RANKL) and nuclear factor of
      activated T cells, cytoplasmic 1 (NFATc1). Hiziki extract also prevented alveolar
      bone loss in a ligature-induced periodontitis rat model through reducing the
      distance between cementoenamel junction and alveolar bone crest (CBJ-ABC) and
      furcation involvement. These findings suggested that hiziki extract has
      prophylactic potential for the prevention of periodontitis through anti
      inflammation and, anti-bone resorption effects and the inhibition of alveolar
      bone destruction.

PMID- 29656308
TI  - Bacterial Lipid Modification of ICP11 and a New ELISA System Applicable for WSSV
      Infection Detection.
AB  - In ELISA, a popular analytical diagnostic tool, the stable non-covalent
      immobilization (coating) of hydrophilic proteins/peptides on to hydrophobic
      polystyrene surface has remained a major common challenge. Recombinant bacterial
      lipid modification of proteins in Escherichia coli system has been shown in this
      study to solve this problem owing to the hydrophobic anchorage provided by three
      fatty acyl groups in N-acyl-S-diacylglyceryl Cys at the N-terminus. Exploiting
      this first post-translational protein engineering, the most abundantly expressed
      white spot syndrome viral protein ICP11 was lipid-modified and tested as a new
      target in a new ELISA method useful to shrimp farming. The lipid served as a
      potent adjuvant to enhance the titer (16 times) of higher affinity antibodies
      where amino terminal lipoamino acid N-acyl-S-diacylglyceryl cysteine of bacterial
      lipoproteins induce inflammatory responses through TLR and stimulate humoral
      immune responses without additional adjuvant and also aided in the immobilization
      of even a few nanograms of ICP11. Competition between the immobilized and the
      free antigen from the sample provided a sensitive measure of antigen in the
      infected shrimp tissues. The detection limit for ICP11 protein using competitive
      ELISA was 250 pg and the linear range of the assay was 15-240 ng.

PMID- 29656309
TI  - Serious adverse drug reactions with sacubitril/valsartan Entresto(r): a French
      pharmacovigilance survey.

PMID- 29656310
TI  - Emission of heavy metals from an urban catchment into receiving water and
      possibility of its limitation on the example of Lodz city.
AB  - Heavy metals are among the priority pollutants which may have toxic effects on
      receiving water bodies. They are detected in most of samples of stormwater
      runoff, but the concentrations are very variable. This paper presents results of
      study on the amount of heavy metals discharged from urban catchment in Lodz
      (Poland) in 2011-2013. The research was carried out to identify the most
      important sources of their emission and to assess the threats to receiving water
      quality and opportunities of their limitation. The city is equipped with a
      combined sewerage in the center with 18 combined sewer overflows and with
      separate system in other parts. Stormwater and wastewater from both systems are
      discharged into 18 small urban rivers. There is a need of restoration of water
      bodies in the city. Research results indicate that the main issue is high
      emission of heavy metals, especially zinc and copper, contained in stormwater.
      Annual mass loads (g/ha/year) from separate system were 1629 for Zn and 305 for
      Cu. It was estimated that about 48% of the annual load of Zn, 38% of Cu, 61% of
      Pb, and 40% of Cd discharged into receiving water came from separate system,
      respectively 4% of Zn and Cu, 10% of Pb and 11% of Cd from CSOs, and the
      remaining part from wastewater treatment plant. Effective reduction of heavy
      metals loads discharged into receiving water requires knowledge of sources and
      emissions for each catchment. Obtained data may indicate the need to apply
      centralized solution or decentralized by source control.

PMID- 29656312
TI  - Evaluation of taurine neuroprotection in aged rats with traumatic brain injury.
AB  - Despite higher rates of hospitalization and mortality following traumatic brain
      injury (TBI) in patients over 65 years old, older patients remain
      underrepresented in drug development studies. Worse outcomes in older individuals
      compared to younger adults could be attributed to exacerbated injury mechanisms
      including oxidative stress, inflammation, blood-brain barrier disruption, and
      bioenergetic dysfunction. Accordingly, pleiotropic treatments are attractive
      candidates for neuroprotection. Taurine, an endogenous amino acid with
      antioxidant, anti-inflammatory, anti-apoptotic, osmolytic, and neuromodulator
      effects, is neuroprotective in adult rats with TBI. However, its effects in the
      aged brain have not been evaluated. We subjected aged male rats to a unilateral
      controlled cortical impact injury to the sensorimotor cortex, and randomized them
      into four treatment groups: saline or 25 mg/kg, 50 mg/kg, or 200 mg/kg i.p.
      taurine. Treatments were administered 20 min post-injury and daily for 7 days. We
      assessed sensorimotor function on post-TBI days 1-14 and tissue loss on day 14
      using T2-weighted magnetic resonance imaging. Experimenters were blinded to the
      treatment group for the duration of the study. We did not observe neuroprotective
      effects of taurine on functional impairment or tissue loss in aged rats after
      TBI. These findings in aged rats are in contrast to previous reports of taurine
      neuroprotection in younger animals. Advanced age is an important variable for
      drug development studies in TBI, and further research is required to better
      understand how aging may influence mechanisms of taurine neuroprotection.

PMID- 29656313
TI  - Re-treatment versus extended treatment strategy of systemic bevacizumab in
      hereditary hemorrhagic telangiectasia: which is better?

PMID- 29656314
TI  - - 174 G>C IL-6 polymorphism and primary iron overload in male patients.
AB  - Primary iron overload (IO) is commonly associated with mutations in the
      hereditary hemochromatosis gene (HFE). Nonetheless, other genetic variants may
      influence the development of IO beyond HFE mutations. There is a single
      nucleotide polymorphism (SNP) at - 174 G>C of the interleukin (IL)-6 gene which
      might be associated with primary IO. Our aim was to study the association between
      the SNP - 174 G>C gene promoter of IL-6 and primary IO in middle-aged male
      patients. We studied 37 men with primary IO diagnosed by liver histology.
      Controls were age-matched male volunteers (n = 37). HFE mutations and the SNP -
      174 G>C gene promoter of IL-6 were evaluated by PCR-RFLP. Logistic regression was
      used to evaluate the association between primary IO and SNP - 174 G>C gene
      promoter of IL-6. Patients and control subjects were in Hardy-Weinberg
      equilibrium for the SNP - 174 G>C gene promoter of IL-6 (p = 0.17). Significantly
      different genotype frequencies were observed between patients (43% CC, 43% CG,
      and 14% GG) and control subjects (10% CC, 41% CG, and 49% GG) (OR = 4.09, 95% CI
      = 2.06-8.13; p < 0.0001). The multiple logistic regression analysis showed that
      IO was significantly associated with CC homozygosis in the SNP - 174 G>C gene
      promoter of IL-6 (OR = 6.3, 95% CI = 1.9-21.4; p < 0.005) in a model adjusted by
      age and body mass index. In conclusion, CC homozygosis in the SNP - 174 G>C gene
      promoter of IL-6 can be proposed as one of the gene variants influencing iron
      accumulation in male adults with HFE mutations. Studies in larger cohorts are
      warranted.

PMID- 29656315
TI  - Acamprosate Protects Against Adjuvant-Induced Arthritis in Rats via Blocking the
      ERK/MAPK and NF-kappaB Signaling Pathway.
AB  - Osteoarthritis is a type of joint disease that results from the breakdown of
      joint cartilage and underlying bone and is believed to be caused by mechanical
      stress on the joint and low-grade inflammatory processes. Acamprosate
      significantly ameliorates the pathological features of experimental autoimmune
      encephalomyelitis due to its anti-inflammatory effect. The aims of the present
      study were to investigate the anti-arthritis activities of acamprosate and
      elucidate the underlying mechanisms. Adjuvant-induced arthritis (AIA) was induced
      by intradermal injection of complete Freund's adjuvant. Male Wistar rats were
      randomly divided into five groups: (1) sham control group, (2) AIA group, (3)
      acamprosate 10 mg/kg (AIA + ACA10), (4) acamprosate 30 mg/kg (AIA + ACA30), and
      (5) acamprosate 100 mg/kg (AIA + ACA100). Paw swelling and the arthritis index
      were measured, and the production of IL-1beta, IL-6, and TNF-alpha was detected
      by ELISA in serum. The expression of inflammation-related molecules, including c
      Raf, ERK1/2, and NF-kappaB, was determined by Western blotting. We found that
      acamprosate significantly suppressed paw swelling and the arthritis index in AIA
      rats. Moreover, acamprosate also significantly suppressed the production of TNF
      alpha, IL-1beta, and IL-6 in serum, which is elevated by AIA induction. Finally,
      acamprosate inhibited p-c-Raf and p-ERK1/2 and NF-kappaB activation after AIA
      treatment. These results indicate that acamprosate has an anti-inflammatory
      effect on adjuvant-induced arthritic rats via inhibiting the ERK/MAPK and NF
      kappaB signaling pathways, and acamprosate may serve as a promising novel
      therapeutic agent for osteoarthritis.

PMID- 29656311
TI  - Consensus Paper: Neurophysiological Assessments of Ataxias in Daily Practice.
AB  - The purpose of this consensus paper is to review electrophysiological
      abnormalities and to provide a guideline of neurophysiological assessments in
      cerebellar ataxias. All authors agree that standard electrophysiological methods
      should be systematically applied in all cases of ataxia to reveal accompanying
      peripheral neuropathy, the involvement of the dorsal columns, pyramidal tracts
      and the brainstem. Electroencephalography should also be considered, although
      findings are frequently non-specific. Electrophysiology helps define the neuronal
      systems affected by the disease in an individual patient and to understand the
      phenotypes of the different types of ataxia on a more general level. As yet,
      there is no established electrophysiological measure which is sensitive and
      specific of cerebellar dysfunction in ataxias. The authors agree that cerebellar
      brain inhibition (CBI), which is based on a paired-pulse transcranial magnetic
      stimulation (TMS) paradigm assessing cerebellar-cortical connectivity, is likely
      a useful measure of cerebellar function. Although its role in the investigation
      and diagnoses of different types of ataxias is unclear, it will be of interest to
      study its utility in this type of conditions. The authors agree that detailed
      clinical examination reveals core features of ataxia (i.e., dysarthria, truncal,
      gait and limb ataxia, oculomotor dysfunction) and is sufficient for formulating a
      differential diagnosis. Clinical assessment of oculomotor function, especially
      saccades and the vestibulo-ocular reflex (VOR) which are most easily examined
      both at the bedside and with quantitative testing techniques, is of particular
      help for differential diagnosis in many cases. Pure clinical measures, however,
      are not sensitive enough to reveal minute fluctuations or early treatment
      response as most relevant for pre-clinical stages of disease which might be
      amenable to study in future intervention trials. The authors agree that
      quantitative measures of ataxia are desirable as biomarkers. Methods are
      discussed that allow quantification of ataxia in laboratory as well as in
      clinical and real-life settings, for instance at the patients' home. Future
      studies are needed to demonstrate their usefulness as biomarkers in
      pharmaceutical or rehabilitation trials.

PMID- 29656316
TI  - The Role of Adenosine Receptor Activation in Attenuating Cartilaginous
      Inflammation.
AB  - Adenosine receptor activation has been explored as a modulator of the
      inflammatory process that propagates osteoarthritis. It has been reported that
      cartilage has enhanced regenerative potential when influenced by adenosine
      receptor activation. As adenosine's role in maintaining chondrocyte homeostasis
      at the cellular and molecular levels is explored, successful in vivo applications
      of adenosine delivery for cartilage repair continue to be reported. This review
      summarizes the role adenosine receptor ligation plays in chondrocyte homeostasis
      and regeneration of articular cartilage damaged in osteoarthritis. It also
      reports on all the modalities reported for delivery of adenosine through in vivo
      applications.

PMID- 29656317
TI  - Inflammatory Response of Pulmonary Artery Smooth Muscle Cells Exposed to
      Oxidative and Biophysical Stress.
AB  - Pulmonary hypertension in the neonate requires treatment with oxygen and positive
      pressure ventilation, both known to induce lung injury. The direct response of
      pulmonary artery smooth muscle cells, the most abundant cells in the artery wall,
      to the stress of positive pressure and hyperoxia has not been previously studied.
      Pulmonary artery smooth muscle cells were cultured in temperature- and pressure
      controlled air-tight chambers under conditions of positive pressure or hyperoxia
      for 24 h. Control cells were cultured in room air under atmospheric pressure.
      After the exposure period, culture medium was collected and samples were analyzed
      by ELISA, Human Cytokine 25-Plex Panel using a Luminex 200 analyzer and Western
      blot. Secretion of various inflammatory mediators, specifically IL-6, IL-8, IL
      2R, MIP-1beta, MCP-1, IP-10, IL-7, IL-1RA, and IFN-alpha, was higher in the
      positive pressure and hyperoxia groups compared with control. The level of cyclin
      D1 was decreased in the hyperoxia and positive pressure group compared with
      control. Levels of fibronectin and alpha-smooth muscle actin were not different
      among the groups. Pulmonary artery smooth muscle cells directly produce multiple
      inflammatory mediators in response to oxidative and biophysical stress in vitro,
      which may be part of a cascade that leads to the vascular and perivascular
      changes in pulmonary hypertension.

PMID- 29656318
TI  - A Novel Tetrasubstituted Imidazole as a Prototype for the Development of Anti
      inflammatory Drugs.
AB  - Although inflammation is a biological phenomenon that exists to protect the host
      against infections and/or related problems, its unceasing activation results in
      the aggravation of several medical conditions. Imidazoles, whether natural or
      synthetic, are molecules related to a broad spectrum of biological effects,
      including anti-inflammatory properties. In this study, we screened eight novel
      small molecules of the imidazole class synthesized by our research group for
      their in vitro anti-inflammatory activity. The effect of the selected molecules
      was confirmed in an in vivo inflammatory model. We also analyzed whether the
      effects were caused by inhibition of nuclear factor kappa B (NF-kappaB)
      transcription factor transmigration. Of the eight imidazoles tested, methyl 1
      allyl-2-(4-fluorophenyl)-5-phenyl-1H-imidazole-4-acetate (8) inhibited nitric
      oxide metabolites and pro-inflammatory cytokine (TNF-alpha, IL-6, and IL-1beta)
      secretion in J774 macrophages stimulated with LPS. It also attenuated leukocyte
      migration and exudate formation in the pleural cavity of mice challenged with
      carrageenan. Furthermore, imidazole 8 reverted the oxidative stress pattern
      triggered by carrageenan in the pleural cavity by diminishing myeloperoxidase,
      superoxide dismutase, catalase, and glutathione S-transferase activities and
      reducing the production of nitric oxide metabolites and thiobarbituric acid
      reactive substances. Finally, these effects can be attributed, at least in part,
      to the ability of this compound to prevent NF-kappaB transmigration. In this
      context, our results demonstrate that imidazole 8 has promising potential as a
      prototype for the development of a new anti-inflammatory drug to treat
      inflammatory conditions in which NF-kappaB and oxidative stress play a prominent
      role. Graphical Abstract ?.

PMID- 29656319
TI  - NLRP3 Inflammasome Involves in the Acute Exacerbation of Patients with Chronic
      Obstructive Pulmonary Disease.
AB  - The NLR pyrin domain-containing protein 3 (NLRP3) inflammasome, a multi-protein
      complex, produces the pro-inflammatory cytokines interleukin (IL)-1beta and IL
      18, which may contribute to the development of airway inflammation in chronic
      obstructive pulmonary disease (COPD). The aim of this study was to explore the
      correlation between circulating and local airway NLRP3 inflammasome activation
      with acute exacerbation of COPD (AECOPD). mRNA levels of NLRP3, Caspase (Casp)-1,
      apoptosis-associated speck-like protein containing CARD (ASC), IL-18, and IL
      1beta in peripheral blood mononuclear cells (PBMCs) and bronchial tissues were
      determined by real-time PCR in 32 smokers, 65 patients with AECOPD, 50 COPD
      patients in recovery stage, and 30 COPD patients in stable stage. The levels of
      IL-1beta and IL-18 in serum and bronchoalveolar lavage fluid (BALF) supernatants
      were measured by ELISA. The load of six common pathogens in BALF samples were
      determined by real-time PCR. The potential correlation between the mRNA levels of
      NLRP3, Casp-1, ASC, IL-18 or IL-1beta and the load of pathogens was evaluated
      individually. Significantly higher mRNA levels of NLRP3, Casp-1, ASC, IL-18, IL
      1beta and higher levels of IL-18 and IL-1beta were found in patients with AECOPD
      than in smokers. These NLRP3 inflammasome mediators were significantly decreased
      when COPD patients in the same group became clinical stable. The increased mRNA
      levels of NLRP3 inflammasomes in bronchial tissues were positively correlated
      with the load of the six common pathogens in the lower respiratory tract. We
      conclude that systemic and local airway NLRP3 inflammasome activation is
      associated with the acute exacerbation, which might be predictive factors of the
      acute exacerbation and clinical outcomes in COPD patients.

PMID- 29656321
TI  - Multi-center reproducibility of structural, diffusion tensor, and resting state
      functional magnetic resonance imaging measures.
AB  - PURPOSE: The aim of this study is to assess multi-center reproducibility and
      longitudinal consistency of MRI imaging measurements, as part of a phase III
      longitudinal multi-center study comparing the neurotoxic effect following
      prophylactic cranial irradiation with hippocampal avoidance (HA-PCI), in
      comparison with conventional PCI in patients with small-cell lung cancer.
      METHODS: Harmonized MRI acquisition protocols from six participating sites and
      two different vendors were compared using both physical and human phantoms. We
      assessed variability across sites and time points by evaluating various phantoms
      and data including hippocampal volume, diffusion metrics, and resting-state fMRI,
      from two healthy volunteers. RESULTS: We report average coefficients of variation
      (CV) below 5% for intrascanner, intravendor, and intervendor reproducibility for
      both structural and diffusion imaging metrics, except for diffusion metrics
      obtained from tractography with average CVs ranging up to 7.8%. Additionally,
      resting-state fMRI showed stable temporal SNR and reliable generation of subjects
      DMN across vendors and time points. CONCLUSION: These findings indicate that the
      presented multi-site MRI acquisition protocol can be used in a longitudinal study
      design and that pooling of the acquired data as part of the phase III
      longitudinal HA-PCI project is possible with careful monitoring of the results of
      the half-yearly QA assessment to follow-up on potential scanner-related
      longitudinal changes in image quality.

PMID- 29656320
TI  - The Role of Mesothelin as a Diagnostic and Therapeutic Target in Pancreatic
      Ductal Adenocarcinoma: A Comprehensive Review.
AB  - Mesothelin is a tumor differentiation antigen, which is highly expressed in
      several solid neoplasms, including pancreatic cancer. Its selective expression on
      malignant cells and on only a limited number of healthy tissues has made it an
      interesting candidate for investigation as a diagnostic and prognostic biomarker
      and as a therapeutic target. Based on a strong preclinical rationale, a number of
      therapeutic agents targeting mesothelin have entered clinical trials, including
      immunotoxins, monoclonal antibodies, antibody-drug conjugates, cancer vaccines,
      and adoptive T cell therapies with chimeric antigen receptors. In pancreatic
      cancer, mesothelin has been investigated mainly to address two unmet issues: the
      urgent need for new laboratory techniques for early tumor detection and the lack
      of successfully targetable oncogenic alterations for patients' treatment. In this
      review, we describe the clinicopathological significance of mesothelin expression
      in pancreatic cancer initiation and progression, we summarize available studies
      evaluating mesothelin as a potential diagnostic and prognostic biomarker in this
      disease, and we discuss current evidence and future perspectives of preclinical
      and clinical studies testing mesothelin as a molecular target for pancreatic
      cancer treatment.

PMID- 29656322
TI  - P190RhoGAP prevents mitotic spindle fragmentation and is required to activate
      Aurora A kinase at acentriolar poles.
AB  - Assembly of the mitotic spindle is essential for proper chromosome segregation
      during mitosis. Maintenance of spindle poles requires precise regulation of
      kinesin- and dynein-generated forces, and improper regulation of these forces
      disrupts pole integrity leading to pole fragmentation. The formation and function
      of the mitotic spindle are regulated by many proteins, including Aurora A kinase
      and the motor proteins Kif2a and Eg5. Here, we characterize a surprising role for
      the RhoA GTPase-activating protein, p190RhoGAP, in regulating the mitotic
      spindle. We show that cells depleted of p190RhoGAP arrest for long periods in
      mitosis during which cells go through multiple transitions between having bipolar
      and multipolar spindles. Most of the p190RhoGAP-depleted cells finally achieve a
      stable bipolar attachment and proceed through anaphase. The multipolar spindle
      phenotype can be rescued by low doses of an Eg5 inhibitor. Moreover, we show that
      p190RhoGAP-depleted multipolar cells localize Aurora A to all the poles, but the
      kinase is only activated at the two centriolar poles. Overall, our data identify
      an unappreciated connection between p190RhoGAP and the proteins that control
      spindle poles including Aurora A kinase and Eg5 that is required to prevent or
      correct spindle pole fragmentation.

PMID- 29656323
TI  - Study of carbon nanotube-rich impedimetric recognition electrode for ultra-low
      determination of polycyclic aromatic hydrocarbons in water.
AB  - Carbon nanotubes (CNTs) have been studied as an electrochemical recognition
      element for the impedimetric determination of priority polycyclic aromatic
      hydrocarbons (PAHs) in water, using hexocyanoferrate as a redox probe. For this
      goal, an indium tin oxide (ITO) electrode functionalized with a silane-based self
      assembled monolayer carrying CNTs has been engineered. The electroanalytical
      method, which is similar to an antibody-antigen assay, is straightforward and
      exploits the high CNT-PAH affinity obtained via pi-interactions. After optimizing
      the experimental conditions, the resulting CNT-based impedimetric recognition
      platform exhibits ultra-low detection limits (1.75 +/- 0.04 ng.L-1) for the sum
      of PAHs tested, which was also validated by using a certified reference PAH
      mixture. Graphical abstract Schematic of an indium-tin-oxide (ITO) electrode
      functionalized with a silane-based self-assembled monolayer carrying carbon
      nanotubes (CNTs) as a recognition platform for the ultra-low determination of
      total polycyclic aromatic hydrocarbons (PAHs) in water via pi-interactions using
      Electrochemical Impedance Spectroscopy (EIS).

PMID- 29656325
TI  - Dosing of the second-generation cryoballoon using acute time-to-pulmonary vein
      isolation as an indicator of durable ablation in a canine model.
AB  - BACKGROUND: Rigid time-based dosing protocol(s) currently used in the clinic for
      cryoballoon ablation of atrial fibrillation may be inadequate to guide the
      circumferential and transmural cryothermal energy transfer across the pulmonary
      vein (PV) and may result in injury to collateral tissues or electrical gaps
      between the PV and left atrium (LA). OBJECTIVE: A physiologic endpoint (e.g.,
      acute time-to-PV isolation a.k.a. time-to-effect; TTE) may be effective in the
      determination of a transmural lesion formation and may allow for individualized
      ablation dosing across each PV. METHODS: Thirty PVs from 15 dogs were randomized
      into five dosing protocols, including (1) TTE + 60 s, (2) TTE + 90 s, (3) TTE +
      120 s, (4) TTE + 150 s, and (5) 2 * 180 s. Ablations were conducted with a 23-mm
      second-generation cryoballoon, and TTE was assessed during a freeze by pacing
      from an inner balloon-lumen circular diagnostic catheter to a quadripolar
      diagnostic catheter in the coronary sinus. After ablation, animals were survived
      for 30 to 34 days, and repeat electrophysiology assessment of PV isolation was
      conducted after which animals were euthanized for gross anatomy and histological
      examination. RESULTS: At study termination, efficacy endpoint evaluations were
      based on maintenance of PV electrical isolation, gross anatomy assessment of PV
      lesions, and histological examination of PVs. Five efficacy endpoint failures
      were noted, including the following: 1 PV in the TTE + 90 sec group; 2 PVs in the
      TTE + 120 sec group; 1 PV in the TTE + 150 s group; and 1 PV in the 2 * 180 s
      group. Regarding safety, one phrenic nerve injury was observed in the 2 * 180 s
      cohort. No other complications were observed. CONCLUSIONS: In a canine model,
      effective PV isolation could be found even in the shortest duration dosing cohort
      (TTE + 60 s). One complication (phrenic nerve injury) was observed in the longest
      duration dosing group (2 * 180 s). Further studies will be required to correlate
      these results to a 28-mm cryoballoon (more commonly used in the cryoablation of a
      human LA); however, to date, this is the first reporting of a successful
      cryoablation using TTE + 60 s dosing (approximately 90 s total duration of
      freezing).

PMID- 29656324
TI  - The organic pollutant status of rivers in Bosnia and Herzegovina as determined by
      a combination of active and passive sampling methods.
AB  - There is an overall lack of data concerning the pollution status of Bosnia
      Herzegovina, which is confounded by fragmented national environmental management.
      The present study aimed to provide some initial data for concentrations of
      priority substances in two major Bosnian Rivers, using two types of passive
      sampler (PS) as well as by using high volume water sampling (HVWS). Overall,
      concentrations of most persistent organic pollutants (POPs), including
      polychlorinated biphenyls (PCBs) and legacy pesticides, were shown to be low.
      However, around the town of Doboj on the Bosna River, concentrations of
      polycyclic aromatic hydrocarbons (PAH) breached European standards for several
      compounds and reached 67 ng L-1 for freely dissolved concentrations and 250 ng L
      1 for total concentrations. In general, contamination was lower in the Neretva
      River compared to the Bosna, although for brominated diphenyl ethers (PBDEs),
      results suggested an active source of PBDEs at one location based on the ratio of
      congeners 47 and 99. Direct comparisons between the different sampling techniques
      used are not straightforward, but similar patterns of PAH contamination were
      shown by HVWS and PS in the Bosna River. There are both scientific and practical
      considerations when choosing which type of sampling technique to apply, and this
      should be decided based on the goals of each individual study.

PMID- 29656326
TI  - The impact of the CartoSound(r) image directly acquired from the left atrium for
      integration in atrial fibrillation ablation.
AB  - PURPOSE: Intracardiac echocardiographic (ICE) imaging might be useful for
      integrating three-dimensional computed tomographic (CT) images for left atrial
      (LA) catheter navigation during atrial fibrillation (AF) ablation. However, the
      optimal CT image integration method using ICE has not been established. METHODS:
      This study included 52 AF patients who underwent successful circumferential
      pulmonary vein isolation (CPVI). In all patients, CT image integration was
      performed after the CPVI with the following two methods: (1) using ICE images of
      the LA derived from the right atrium and right ventricular outflow tract (RA
      merge) and (2) using ICE images of the LA directly derived from the LA added to
      the image for the RA-merge (LA-merge). The accuracy of these two methods was
      assessed by the distances between the integrated CT image and ICE image (ICE-to
      CT distance), and between the CT image and actual ablated sites for the CPVI (CT
      to-ABL distance). RESULTS: The mean ICE-to-CT distance was comparable between the
      two methods (RA-merge = 1.6 +/- 0.5 mm, LA-merge = 1.7 +/- 0.4 mm; p = 0.33).
      However, the mean CT-to-ABL distance was shorter for the LA-merge (2.1 +/- 0.6
      mm) than RA-merge (2.5 +/- 0.8 mm; p < 0.01). The LA, especially the left-sided
      PVs and LA roof, was more sharply delineated by direct LA imaging, and whereas
      the greatest CT-to-ABL distance was observed at the roof portion of the left
      superior PV (3.7 +/- 2.8 mm) after the RA-merge, it improved to 2.6 +/- 1.9 mm
      after the LA-merge (p < 0.01). CONCLUSIONS: Additional ICE images of the LA
      directly acquired from the LA might lead to a greater accuracy of the CT image
      integration for the CVPI.

PMID- 29656327
TI  - Analysis of regeneration- and myelination-associated proteins in human neuroma in
      continuity and discontinuity.
AB  - BACKGROUND: Neuromas are pathologic nerve distensions caused by a nerve's
      response to trauma, resulting in a dysfunctional to non-functional nerve.
      Depending on the severance of the affected nerve, the resulting neuroma can be
      differentiated into continuous and stump neuroma. While neuroma formation has
      been investigated in animal models with enormous regenerative capacity, the
      search for differences in human response to nerve trauma on a molecular level
      ultimately seeks to identify reasons for functionally successful versus
      unsuccessful regeneration after peripheral nerve trauma in man. METHODS: In the
      present study, the regenerative potential of axons and the capability of Schwann
      cells (SC) to remyelinate regenerating axons was quantitatively and segmentally
      analyzed and compared within human neuroma in-continuity and discontinuity.
      RESULTS: For the stump neuroma and the neuroma in-continuity, there was a
      significant reduction of the total number of axons (86% stump neuroma and 91%
      neuroma in-continuity) from the proximal to the distal part of the neuroma, while
      the amount of fibrotic tissue increased, respectively. Labeling the myelin sheath
      of regenerating axons revealed a remyelination of regenerating axons by SCs in
      both neuroma types. The segmented analysis showed no distinct alterations in the
      number and spatial distribution of regenerating, mature, and myelinated axons
      between continuous and discontinuous neuroma. CONCLUSIONS: The quantitative and
      segmented analysis showed no distinct alterations in the number and spatial
      distribution of regenerating, mature, and myelinated axons between continuous and
      discontinuous neuroma, while the extensive expression of Gap43 in up to 55% of
      the human neuroma axons underlines their regenerative capacity independent of
      whether the neuroma is in continuity or discontinuity. Remyelination of Gap43
      positive axons suggests that the capability of SCs to remyelinate regenerating
      axons is preserved in neuroma tissue.

PMID- 29656328
TI  - Human colostrum action against Giardia lamblia infection influenced by hormones
      and advanced maternal age.
AB  - Children are more susceptible to Giardia lamblia infection. Cells and hormones
      contained in human colostrum have an immunoprotective action against giardiasis,
      but the effects of advanced maternal age on these components are poorly
      understood. This study analyzed the colostrum of older women to determine
      melatonin and cortisol levels besides the participation of these hormones on the
      functional activity of phagocytes against G. lamblia. Colostrum samples were
      collected from younger (18 to 35 years old) and older (over 36 years old)
      lactating women. Colostrum samples were subjected to melatonin and cortisol
      determination, immunophenotyping, quantification of superoxide release, and
      assessment of phagocytic rate and microbicidal activity of phagocytes treated
      with hormones and in the presence of G. lamblia. Colostrum from mothers of
      advanced age contained higher melatonin and cortisol levels and a lower rate of
      cells expressing CD14+ and CD15+. In the colostru of these older mothers,
      melatonin increased superoxide release by phagocytes. In both groups, superoxide
      release by phagocytes treated with cortisol was higher in the presence of G.
      lamblia. In colostrum from mothers of advanced age, mononuclear (MN) phagocytes
      treated with melatonin showed higher phagocytosis of G. lamblia and higher
      microbicidal index. In younger mothers, MN and polymorphonuclear (PMN) colostrum
      phagocytes exhibited higher rates of G. lamblia elimination when treated with
      both melatonin and cortisol. In older mothers, cortisol and melatonin regulation
      for the functional activity of colostrum phagocytes against G. lamblia may
      represent an additional defense mechanism, relevant for the protection and
      treatment of parasitic infections in breastfed children.

PMID- 29656329
TI  - Comparison of perioperative and oncological outcome of thoracoscopic
      esophagectomy in left decubitus position and in prone position for esophageal
      cancer.
AB  - PURPOSE: The aim of this study was to clarify the differences between
      thoracoscopic esophagectomy in the left decubitus position (LP) and in the prone
      position (PP) in terms of short-term perioperative outcomes and long-term
      oncological outcomes after more than 5 years of follow-up. METHODS: Patients with
      esophageal cancer who underwent thoracoscopic esophagectomy and were followed up
      for more than 5 years were analyzed retrospectively. Of 142 patients, 72
      underwent LP esophagectomy and 70 underwent PP esophagectomy. Operation time,
      blood loss, operative morbidity, mortality, length of hospital stay, and the
      number of dissected lymph nodes were compared to evaluate short-term outcomes.
      Cancer recurrence and overall survival were compared to examine long-term
      outcomes. RESULTS: Patient and tumor characteristics were not different between
      the LP and PP groups except for the rate of neoadjuvant chemotherapy. Blood loss
      was significantly lower in the PP group than in the LP group. Incidence of
      Clavien-Dindo (C.D.) grade >= III complications was significantly lower in the PP
      group than in the LP group. Pulmonary complications were also significantly lower
      in the PP group than in the LP group. Operation type (LP versus PP) was
      identified as an independent risk factor for pulmonary complications (odds ratio
      0.27, p = 0.03) by multivariate analysis. Cancer recurrence rate, initial
      recurrence site, and overall survival rate were not different between the two
      groups. CONCLUSIONS: PP is regarded as a less invasive procedure than LP with the
      same oncological effect.

PMID- 29656330
TI  - Risk factors for anatomic pelvic organ prolapse at 6 weeks postpartum: a
      prospective observational study.
AB  - INTRODUCTION AND HYPOTHESIS: The objective was to identify risk factors for
      postpartum anatomic pelvic organ prolapse (aPOP) by comparing women with and
      without aPOP at 6 weeks postpartum with regard to pelvic floor measurements
      antepartum and obstetrical characteristics. METHODS: We carried out a prospective
      observational cohort study including nulliparous pregnant women in a Norwegian
      university hospital. Participants underwent clinical examinations, including
      pelvic organ prolapse quantification system (POP-Q) and transperineal ultrasound
      at gestational week 21 and at 6 weeks postpartum. Background and obstetrical
      information was obtained from an electronic questionnaire and from the patient's
      electronic medical file respectively. Associations were estimated using logistic
      regression analyses. The dependent variable was aPOP, defined as POP-Q stage >=2
      at 6 weeks postpartum. Independent variables were mid-pregnancy measurements of
      selected POP-Q variables and levator hiatus area (LHarea), delivery route, and
      the presence of major levator ani muscle (LAM) injuries at 6 weeks postpartum.
      RESULTS: A larger LHarea, a more distensible LAM, a longer distance from the
      meatus urethra to the anus (Gh + Pb) and a more caudal position of the anterior
      vaginal wall (Ba) at mid-pregnancy were risk factors for aPOP at 6 weeks
      postpartum, whereas delivery route and the presence of major LAM injuries were
      not. CONCLUSION: Prelabor differences in the pelvic floor rather than obstetrical
      events were risk factors for aPOP at 6 weeks postpartum.

PMID- 29656331
TI  - Survey of pelvic reconstructive surgeons on performance of opportunistic
      salpingectomy at the time of pelvic organ prolapse repair.
AB  - INTRODUCTION AND HYPOTHESIS: Opportunistic salpingectomy (OS) at the time of
      benign hysterectomy has recently emerged as a potential primary preventive
      modality for ovarian cancer. Our objective was to determine whether the reported
      rate of OS at the time of prolapse surgery is similar to the rate of OS at the
      time of gynecologic surgery for non-prolapse indications. METHODS: An anonymous
      online survey was sent to the Society of Gynecologic Surgery members. Responses
      were divided into surgeons who did and did not perform OS at the time of prolapse
      repair. Differences between surgeons who did and did not perform OS were
      evaluated using the chi-square test. Multivariable logistic regression was used
      to identify which responses related to increased odds of performing OS. RESULTS:
      There were 117 (33.1%) completed responses; of these, 98 (83.8%) reported
      performing OS at the time of prolapse repair, which was similar to the reported
      rate of OS at the time of hysterectomy for non-prolapse indications, 82.1%. After
      multivariable logistic regression, performance of salpingectomy at the time of
      hysterectomy for a non-prolapse indication (aOR: 17.9, 95% CI: 3.11-42.01), use
      of a laparoscopic or robotic surgical approach (aOR 14.1, 95% CI: 1.81-32.21) and
      completion of an FPMRS fellowship (aOR: 3.47, 95% CI: 1.20-10.02) were associated
      with a higher likelihood of performing OS at the time of prolapse repair.
      CONCLUSIONS: OS at the time prolapse repair is performed more frequently with
      concomitant hysterectomy compared with OS at the time of post-hysterectomy
      prolapse repair and is similar to rates of OS performed at the time of
      hysterectomy for non-prolapse indications.

PMID- 29656332
TI  - Rdh13 deficiency weakens carbon tetrachloride-induced liver injury by regulating
      Spot14 and Cyp2e1 expression levels.
AB  - Mitochondrion-localized retinol dehydrogenase 13 (Rdh13) is a short-chain
      dehydrogenase/reductase involved in vitamin A metabolism in both humans and mice.
      We previously generated Rdh13 knockout mice and showed that Rdh13 deficiency
      causes severe acute retinal light damage. In this study, considering that Rdh13
      is highly expressed in mouse liver, we further evaluated the potential effect of
      Rdh13 on liver injury induced by carbon tetrachloride (CCl4). Although Rdh13
      deficiency showed no significant effect on liver histology and physiological
      functions under regular culture, the Rdh13-/- mice displayed an attenuated
      response to CCl4-induced liver injury. Their livers also exhibited less
      histological changes and contained lower levels of liver-related metabolism
      enzymes compared with the livers of wild-type (WT) mice. Furthermore, the Rdh13-/
      mice had Rdh13 deficiency and thus their liver cells were protected from
      apoptosis, and the quantity of their proliferative cells became lower than that
      in WTafter CCl4 exposure. The ablation of Rdh13 gene decreased the expression
      levels of thyroid hormone-inducible nuclear protein 14 (Spot14) and cytochrome
      P450 (Cyp2e1) in the liver, especially after CCl4 treatment for 48 h. These data
      suggested that the alleviated liver damage induced by CCl4 in Rdh13-/- mice was
      caused by Cyp2e1 enzymes, which promoted reductive CCl4 metabolism by altering
      the status of thyroxine metabolism. This result further implicated Rdh13 as a
      potential drug target in preventing chemically induced liver injury.

PMID- 29656333
TI  - Interferon-alpha salvage treatment is effective for patients with acute
      leukemia/myelodysplastic syndrome with unsatisfactory response to minimal
      residual disease-directed donor lymphocyte infusion after allogeneic
      hematopoietic stem cell transplantation.
AB  - The efficacy of salvage interferon-alpha (IFN-alpha) treatment was investigated
      in patients with unsatisfactory response to minimal residual disease (MRD)
      directed donor lymphocyte infusion (DLI) (n = 24). Patients who did not become
      MRD-negative at 1 month after DLI were those with unsatisfactory response and
      were eligible to receive salvage IFN-alpha treatment within 3 months of DLI.
      Recombinant human IFN-alpha-2b injections were subcutaneously administered 2-3
      times a week for 6 months. Nine (37.5%), 6 (25.0%), and 3 (12.5%) patients became
      MRD-negative at 1, 2, and > 2 months after the salvage IFN-alpha treatment,
      respectively. Two-year cumulative incidences of relapse and non-relapse mortality
      were 35.9% and 8.3%, respectively. Two-year probabilities of event-free survival,
      disease-free survival, and overall survival were 51.6%, 54.3%, and 68.0%,
      respectively. Outcomes of patients subjected to salvage IFN-alpha treatment after
      DLI were significantly better than those with persistent MRD without IFN-alpha
      treatment. Moreover, clinical outcomes were comparable between the salvage DLI
      and IFN-alpha treatment groups. Thus, salvage IFN-alpha treatment may help
      improve the outcome of patients with unsatisfactory responses to MRD-directed DLI
      and could be a potential salvage treatment for these patients after allogeneic
      hematopoietic stem cell transplantation.

PMID- 29656334
TI  - Four Gaucher disease type II patients with three novel mutations: a single centre
      experience from Turkey.
AB  - Gaucher disease is the most common lysosomal storage disorder due to
      glucosylceramidase enzyme deficiency. There are three subtypes of the disease.
      Neurological involvement accompanies visceral and haematological findings only in
      type II and type III Gaucher patients. Type II is the acute progressive
      neuronopathic form which is the most severe and rare subtype. Clinical findings
      are recognized prenatally or in the first months of life and followed by death
      within the first two years of age. Among our 81 Gaucher patients, we identified 4
      (4,9%) type II patients in our metabolic centre. This rate is significantly
      higher than the rate reported in the literature (<1%). Three of the patients had
      novel mutations, one of them was a collodion baby and the other one was mistyped
      as type III due to its atypical presentation at the beginning and he was treated
      with ERT for 8 months. In this report, we present our type II Gaucher patients
      with three novel mutations and one perinatal lethal form with generalized
      ichthyosis which is a very rare disorder. Additionally, we would like to
      highlight the phenotypic heterogeneity not only between the subtypes, also even
      in the same type.

PMID- 29656335
TI  - Role of microglia under cardiac and cerebral ischemia/reperfusion (I/R) injury.
AB  - Both cerebral and cardiac ischemia causes loss of cerebral blood flow, which may
      lead to neuronal cell damage, neurocognitive impairment, learning and memory
      difficulties, neurological deficits, and brain death. Although reperfusion is
      required immediately to restore the blood supply to the brain, it could lead to
      several detrimental effects on the brain. Several studies demonstrate that
      microglia activity increases following cerebral and cardiac ischemic/reperfusion
      (I/R) injury. However, the effects of microglial activation in the brain
      following I/R remains unclear. Some reports demonstrated that microglia were
      involved in neurodegeneration and oxidative stress generation, whilst others
      showed that microglia did not respond to I/R injury. Moreover, microglia are
      activated in a time-dependent manner, and in a specific brain region following
      I/R. Recently, several therapeutic approaches including pharmacological
      interventions and electroacupuncture showed the beneficial effects, while some
      interventions such as hyperthermia and hyperoxic resuscitation, demonstrated the
      deteriorated effects on the microglial activity after I/R. Therefore, the present
      review summarized and discussed those studies regarding the effects of global and
      focal cerebral as well as cardiac I/R injury on microglia activation, and the
      therapeutic interventions.

PMID- 29656336
TI  - Combined Immunodeficiency with Ring Chromosome 21.

PMID- 29656337
TI  - Preparation and characterization of sulfonated chitosan-modified gold
      nanoparticles and their surface electronic payload of charged drugs.
AB  - Chitosan (CS), a kind of naturally produced polysaccharide with extraordinary
      biocompatibility and biodegradation, shows much potential to act as reducing and
      stabilizing agent in the synthesis of gold nanoparticles (AuNPs) for drug
      delivery. To solve the poor solubility and expand the pharmaceutical applications
      of CS, various CS derivatives through rational design have been developed and
      further used to prepare, stabilize, and mediate self-assembling of gold
      materials. Herein, we chose sulfonic chitosan as a stabilizing reagent for the
      synthesis of highly stable AuNPs (AuNP/SCSs) with diameters of about 3 nm. For
      investigating their surface electronic payload of charged drugs, the negatively
      charged fluorescence isothiocyanate (FITC) and positively charged Rhodamine B
      (Rb) were used as models to be modified on the surface of the AuNP/SCSs via a
      layer-by-layer (LbL) method. With a basis of the fluorescence resonance energy
      transfer (FRET) principle, via adjusting the distance between AuNPs and
      fluorescent molecules by tuning the layers of charged polymers, the regulation of
      the fluorescence intensity of the fluorescent molecules has been achieved. In
      addition, the drug loading efficiency was investigated.

PMID- 29656338
TI  - Morphology of living cells cultured on nanowire arrays with varying nanowire
      densities and diameters.
AB  - Vertical nanowire arrays are increasingly investigated for their applications in
      steering cell behavior. The geometry of the array is an important parameter,
      which influences the morphology and adhesion of cells. Here, we investigate the
      effects of array geometry on the morphology of MCF7 cancer cells and MCF10A
      normal-like epithelial cells. Different gallium phosphide nanowire array
      geometries were produced by varying the nanowire density and diameter. Our
      results show that the cell size is smaller on nanowires compared to flat gallium
      phosphide. The cell area decreases with increasing the nanowire density on the
      substrate. We observed an effect of the nanowire diameter on MCF10A cells, with a
      decreased cell area on 40 nm diameter nanowires, compared to 60 and 80 nm
      diameter nanowires in high-density arrays. The focal adhesion morphology depends
      on the extent to which cells are contacting the substrate. For low nanowire
      densities and diameters, cells are lying on the substrate and we observed large
      focal adhesions at the cell edges. In contrast, for high nanowire densities and
      diameters, cells are lying on top of the nanowires and we observed point-like
      focal adhesions distributed over the whole cell. Our results constitute a step
      towards the ability to fine-tune cell behavior on nanowire arrays.

PMID- 29656339
TI  - Role of AMPK in atherosclerosis via autophagy regulation.
AB  - Atherosclerosis is characterized by the accumulation of lipids and deposition of
      fibrous elements in the vascular wall, which is the primary cause of
      cardiovascular diseases. Adenosine monophosphate-activated protein kinase (AMPK)
      is a metabolic sensor of energy metabolism that regulates multiple physiological
      processes, including lipid and glucose metabolism and the normalization of energy
      imbalances. Overwhelming evidence indicates that AMPK activation markedly
      attenuates atherosclerosis development. Autophagy inhibits cell apoptosis and
      inflammation and promotes cholesterol efflux and efferocytosis. Physiological
      autophagy is essential for maintaining normal cardiovascular function. Increasing
      evidence demonstrates that autophagy occurs in developing atherosclerotic
      plaques. Emerging evidence indicates that AMPK regulates autophagy via a
      downstream signaling pathway. The complex relationship between AMPK and autophagy
      has attracted the attention of many researchers because of this close
      relationship to atherosclerosis development. This review demonstrates the role of
      AMPK and autophagy in atherosclerosis. An improved understanding of this
      interrelationship will create novel preventive and therapeutic strategies for
      atherosclerosis.

PMID- 29656340
TI  - CAPS/dCAPS Designer: a web-based high-throughput dCAPS marker design tool.

PMID- 29656341
TI  - Environmental factors that influence milk production of Pantaneiro ewes and the
      weight gain of their lambs during the pre-weaning period.
AB  - The main objective of this research was to conduct an exploratory study of the
      lactation curve in order to characterize the productive potential of Pantaneiro
      ewes and lambs. Fifty ewes were bred using four rams in two different mating
      seasons. The ewes were kept with their lambs on pasture of Brachiaria brizantha.
      Ewe body score, ewe weight, and lamb weight were evaluated. Milk sampling was
      performed every week. In the morning for milk collections, the ewes were treated
      with 1 UI of oxytocin (intramuscular) for complete milking. Lambs were separated
      from the ewes for 4 h and milk collections were performed. The total milk
      production over 24 h was estimated by multiplying the production of this period
      (4 h) by 6. The data were analyzed using the MIXED procedure (P < 0.05) in SAS.
      Milk production data were fitted to the curve using the incomplete gamma function
      of Wood, and lamb growth data were fitted using the Gompertiz equation. The
      average milk production of the ewes was 1.03 kg/day-1. Younger ewes had the
      lowest milk production (18 = 798 +/- 330, 24 = 1001 +/- 440, 36 = 1100 +/- 490,
      and 48 = 1106 +/- 490 g/day-1). Ewe body score at lambing affected initial milk
      production (1.0 = 816 +/- 660, 1.5 = 1089 +/- 105, and 2.0 = 1424 +/- 1600 g/day
      1). Lambs were weaned with an average weight of 20.3 kg. Daily weight gain from
      birth to weaning was 181 g. Locally adapted Pantaneiro ewes showed a linear
      decreasing lactation curve, with reduced production from the second week of
      lactation. Overall, evaluation of the dairy production and lamb performance
      revealed great variation, denoting potential for selection.

PMID- 29656342
TI  - Prosaposin and its receptors are differentially expressed in the salivary glands
      of male and female rats.
AB  - Salivary glands produce various neurotrophins that are thought to regulate
      salivary function during normal and pathological conditions. Prosaposin (PSAP) is
      a potent neurotrophin found in several tissues and various biological fluids and
      may play roles in the regulation of salivary function. However, little is known
      about PSAP in salivary glands. As the functions of salivary glands are diverse
      based on age and sex, this study examines whether PSAP and its receptors, G
      protein-coupled receptor 37 (GPR37) and GPR37L1, are expressed in the salivary
      glands of rats and whether sex and aging affect their expression.
      Immunohistochemical analysis revealed that PSAP and its receptors were expressed
      in the major salivary glands of rats, although their expression varied
      considerably based on the type of gland, acinar cells, age and sex. In fact,
      PSAP, GPR37 and GPR37L1 were predominantly expressed in granular convoluted
      tubule cells of the submandibular gland and the intensity of their
      immunoreactivity was higher in young adult female rats than age-matched male
      rats, which was more prominent at older ages (mature adult to menopause). On the
      other hand, weak PSAP, GPR37 and GPR37L1 immunoreactivity was observed mainly in
      the basal layer of mucous cells of the sublingual gland. Triple label
      immunofluorescence analysis revealed that PSAP, GPR37 and GPR37L1 were co
      localized in the basal layer of acinar and ductal cells in the major salivary
      glands. The present findings indicate that PSAP and its receptors, GPR37 and
      GPR37L1, are expressed in the major salivary glands of rats and their
      immunoreactivities differ considerably with age and sex.

PMID- 29656343
TI  - Lateralisation in Parkinson disease.
AB  - Asymmetry of dopaminergic neurodegeneration and subsequent lateralisation of
      motor symptoms are distinctive features of Parkinson's disease compared to other
      forms of neurodegenerative or symptomatic parkinsonism. Even 200 years after the
      first description of the disease, the underlying causes for this striking
      clinicopathological feature are not yet fully understood. There is increasing
      evidence that lateralisation of disease is due to a complex interplay of
      hereditary and environmental factors that are reflected not only in the concept
      of dominant hemispheres and handedness but also in specific susceptibilities of
      neuronal subpopulations within the substantia nigra. As a consequence, not only
      the obvious lateralisation of motor symptoms occurs but also patterns of
      associated non-motor signs are defined, which include cognitive functions, sleep
      behaviour or olfaction. Better understanding of the mechanisms contributing to
      lateralisation of neurodegeneration and the resulting patterns of clinical
      phenotypes based on bilateral post-mortem brain analyses and clinical studies
      focusing on right/left hemispheric symptom origin will help to develop more
      targeted therapeutic approaches, taking into account subtypes of PD as a
      heterogeneous disorder.

PMID- 29656344
TI  - Orthotidal signal in the electrical conductivity of an inland river.
AB  - An orthotidal signal is a tidal component found in a streamwater parameter when
      there is no oceanic tidal input, i.e. when the streamwater monitoring point is
      located far inland and at high elevation. This study analyses various parameters
      of Cib River in Carpathian Mountains, Romania. This river receives water from a
      rich karst aquifer when crossing Cib Gorge. Streamwater level, temperature and
      electrical conductivity were measured in 270 days grouped in three time intervals
      of consecutive days. The measurements were done every 15 minutes in order to
      capture any significant periodic variation. The streamwater measurements were
      paired with air measurements and measurements done in a thermal spring. Solar
      semidiurnal oscillations were found in the streamwater electrical conductivity.
      In case study time series, selected based on their good signal to noise ratio,
      there are average semidiurnal oscillations of approximately 4 MUS/cm, while the
      maximum amplitude rise up to 20 MUS/cm. The semidiurnal peaks in water are
      generally in phase with the two atmospheric tide maxima, which are the cause of
      the studied phenomenon. The higher mineralisations of the thermal waters that
      rise from beneath the karst aquifer are the most probable cause of finding
      significant orthotides only in the electrical conductivity time series of the
      studied river.

PMID- 29656345
TI  - Update on the Treatment of Early-Stage Triple-Negative Breast Cancer.
AB  - OPINION STATEMENT: Triple-negative breast cancer (TNBC) accounts for 15% of all
      breast cancers and is associated with poor long-term outcomes compared to other
      breast cancer subtypes. Currently, chemotherapy remains the main modality of
      treatment for early-stage TNBC, as there is no approved targeted therapy for this
      subtype. The biologic heterogeneity of TNBC has hindered the development and
      evaluation of novel agents, but recent advancements in subclassifying TNBC have
      paved the way for further investigation of more effective systemic therapies,
      including cytotoxic and targeted agents. TNBC is enriched for germline BRCA
      mutation and for somatic deficiencies in homologous recombination DNA repair, the
      so-called "BRCAness" phenotype. Together, germline BRCA mutations and BRCAness
      are promising biomarkers of susceptibility to DNA-damaging therapy. Various
      investigational approaches are consequently being investigated in early-stage
      TNBC, including immune checkpoint inhibitors, platinum compounds, PI3K pathway
      inhibitors, and androgen receptor inhibitors. Due to the biological diversity
      found within TNBC, patient selection based on molecular biomarkers could aid the
      design of early-phase clinical trials, ultimately accelerating the clinical
      application of effective new agents. TNBC is an aggressive breast cancer subtype,
      for which multiple targeted approaches will likely be required for patient
      outcomes to be substantially improved.

PMID- 29656346
TI  - Hip fracture patients who experience a greater fluctuation in RDW during hospital
      course are at heightened risk for all-cause mortality: a prospective study with 2
      year follow-up.
AB  - : This study aims to detect whether there remains valuable prognostic information
      in fluctuation of red cell distribution width (RDW) in hip fracture patients.
      Results show that this readily available parameter may provide a more effective
      strategy for assessment of mortality risk, therefore providing a reference for
      clinical planning and decision-making. INTRODUCTION: Prognostic values have been
      found in the fluctuation of some hematologic parameters. The red cell
      distribution width (RDW) routinely reported with all complete blood cell counts
      (CBC) has proven to be associated with poor outcomes in various diseases.
      However, whether the fluctuation in RDW is predictive of long-term mortality in
      hip fracture patients treated with surgery remains unknown. METHODS: One thousand
      three hundred thirty hip fracture patients who underwent surgery from January 1,
      2000 to November 18, 2012 were recruited in this prospective cohort study.
      Fluctuation in the RDW between admission and discharge was measured, and a Kaplan
      Meier (KM) analysis and multivariable Cox regression model were applied to
      evaluate the relationship between this fluctuation and mortality. Risk factors
      for a larger fluctuation were detected by using Logistic regression analyses.
      RESULTS: In addition to the admission RDW, a high RDW level at the time of
      discharge was also associated with an increased risk of death, while no
      significant difference was found in the postoperative RDW. Fluctuation in the RDW
      between admission and discharge was an independent risk predictor for 2-year
      mortality (HR 1.45 95%CI 1.06-2.00, p = 0.022). Factors affecting the change in
      the RDW between admission and discharge included both the demographic
      characteristics of the patients and clinical interventions. CONCLUSION: Hip
      fracture patients who experience a greater fluctuation in RDW during the hospital
      course are at a heightened risk for 2-year all-cause mortality.

PMID- 29656347
TI  - Mediterranean diet and hip fracture incidence among older adults: the CHANCES
      project.
AB  - : The association between adherence to Mediterranean diet (MD) and hip fracture
      incidence is not yet established. In a diverse population of elderly, increased
      adherence to MD was associated with lower hip fracture incidence. Except
      preventing major chronic diseases, adhering to MD might have additional benefits
      in lowering hip fracture risk. INTRODUCTION: Hip fractures constitute a major
      public health problem among older adults. Latest evidence links adherence to
      Mediterranean diet (MD) with reduced hip fracture risk, but still more research
      is needed to elucidate this relationship. The potential association of adherence
      to MD with hip fracture incidence was explored among older adults. METHODS: A
      total of 140,775 adults (116,176 women, 24,599 men) 60 years and older, from five
      cohorts from Europe and the USA, were followed-up for 1,896,219 person-years
      experiencing 5454 hip fractures. Diet was assessed at baseline by validated,
      cohort-specific, food-frequency questionnaires, and hip fractures were
      ascertained through patient registers or telephone interviews/questionnaires.
      Adherence to MD was evaluated by a scoring system on a 10-point scale modified to
      be applied also to non-Mediterranean populations. In order to evaluate the
      association between MD and hip fracture incidence, cohort-specific hazard ratios
      (HR), adjusted for potential confounders, were estimated using Cox proportional
      hazards regression and pooled estimates were subsequently derived implementing
      random-effects meta-analysis. RESULTS: A two-point increase in the score was
      associated with a significant 4% decrease in hip fracture risk (pooled adjusted
      HR 0.96; 95% confidence interval (95% CI) 0.92-0.99, pheterogeneity = 0.446). In
      categorical analyses, hip fracture risk was lower among men and women with
      moderate (HR 0.93; 95% CI 0.87-0.99) and high (HR 0.94; 95% CI 0.87-1.01)
      adherence to the score compared with those with low adherence. CONCLUSIONS: In
      this large sample of older adults from Europe and the USA, increased adherence to
      MD was associated with lower hip fracture incidence.

PMID- 29656348
TI  - Are Digitally Delivered Psychological Interventions for Depression the Way
      Forward? A Review.
AB  - Digitally delivered interventions aim to make psychological treatments more
      widely accessible and minimize clinician input. Although their clinical efficacy
      against wait-list, control conditions is well established, comparative outcome
      studies are a much better way to examine if psychotherapies are equally
      effective. Such reviews are still relatively lacking. The aim of this review was
      therefore to evaluate the effectiveness of digitally delivered psychological
      therapies over traditionally delivered (face-to-face) ones to alleviate symptoms
      in adults experiencing sub-threshold and clinical depression. Findings showed
      that digital interventions produced consistently clinically significant
      improvements in depressive symptoms. Moreover, the level of therapist contact or
      expertise did not affect much treatment effectiveness. Future research is
      pertinent to investigate further the influence of therapist input, the reasons
      for dropout, how to improve users' experience and therapeutic engagement and
      maintain improvements at post-treatment.

PMID- 29656350
TI  - High Content of Lead Is Associated with the Softness of Drinking Water and Raised
      Cardiovascular Morbidity: A Review.
AB  - Daily ingestion of lead (Pb), even through piped drinking water, has long time
      been an important issue of concern, attracting for decades research in
      environmental science and toxicology, and again comes to prominence because of
      recent high-profile cases of exposure of populations in several countries to Pb
      contaminated water. Numerous studies have reported an association between Pb in
      water and the risk of cardiovascular pathologies. Low levels of magnesium and
      calcium, i.e., low degree of hardness of the drinking water, may accentuate Pb
      leaching from water pipes and furthermore increase Pb absorption. This review
      evaluates the evidence for an association between Pb exposure from drinking water
      and cardiovascular end points in human populations.

PMID- 29656351
TI  - Treatment of Colorectal Cancer: a Multidisciplinary Approach.
AB  - BACKGROUND: Colorectal cancer is the third most prevalent cancer in the world,
      preceded by prostate and lung cancers in men (10%) and breast and lung cancers in
      women (9.4%). Colorectal cancer is the fourth leading cause of death in men
      (7.6%) and the third in women (8.6%). A multidisciplinary approach has radically
      changed the way we deal with this disease among all specialist fields. PURPOSE:
      In this study, we propose comparing the multidisciplinary experience group
      (started in 2012) of S. Anna Hospital (University of Ferrara) with the previous
      approach to rectal cancer before the advent of the multidisciplinary program.
      RESULTS: We find that more study depth of neoplastic disease as well as of each
      individual patient leads to more accurate staging and to a weighted therapy based
      on the needs of the individual. All the studies were performed in accordance with
      the guidelines established by the European and Italian associations.

PMID- 29656349
TI  - The Designer Drug 3-Fluoromethcathinone Induces Oxidative Stress and Activates
      Autophagy in HT22 Neuronal Cells.
AB  - Synthetic cathinones are psychoactive substances, derivatives of a natural
      psychostimulant cathinone. Although many synthetic cathinones have lost their
      legal status in many countries, their abuse still continues worldwide. Recently,
      they have been reported to exert neurotoxic effects in vitro and in vivo. The
      molecular mechanisms of their action have not been fully elucidated. Recently,
      they have been linked to the induction of oxidative stress, autophagy, and
      apoptosis. The aim of this study was to investigate whether 3-fluoromethcathinone
      (3-FMC), a synthetic cathinone, is able to induce oxidative stress, autophagy,
      and apoptosis in HT22 immortalized mouse hippocampal cells. We found that
      treatment of HT22 cells with this compound results in a concentration-dependent
      increase in the intracellular production of reactive oxygen species. Moreover, 3
      FMC induced concentration-dependent conversion of cytosolic LC3-I to membrane
      bound LC3-II and formation of autophagic vacuoles. Additionally, the level of
      p62/SQSTM1 protein decreased after 3-FMC treatment, suggesting that accumulation
      of autophagic vacuoles resulted from activation rather than inhibition of
      autophagy. Our results also showed that 3-FMC at millimolar concentration is able
      to induce caspase-dependent apoptotic cell death in HT22 cells. Our findings
      suggest that abuse of 3-FMC may disturb neuronal homeostasis and impair
      functioning of the central nervous system.

PMID- 29656352
TI  - EUS-Guided Biliary Drainage for Unresectable Malignant Biliary Obstruction: 10
      Year Experience of 99 Cases at a Single Center.
AB  - PURPOSE: To evaluate clinical outcomes of endoscopic ultrasound (EUS)-guided
      biliary drainage (EUS-BD) for unresectable malignant biliary obstruction for
      cases in which endoscopic retrograde cholangiopancreatography (ERCP) failed at a
      high-volume center. METHODS: All 99 EUS-BD cases of unresectable malignant
      biliary obstruction at Sendai City Medical Center between February 2007 and
      September 2017 were retrospectively evaluated. ERCP is strictly prioritized over
      EUS-BD during the study period, and EUS-BD was performed in cases wherein ERCP
      was impossible or ineffective. Technical success, clinical success, adverse
      events, and time to recurrence of biliary obstruction were evaluated. RESULTS:
      EUS-BD was technically successful in 98% of the patients (97/99). The clinical
      success rate was 93% (90/97). Adverse events that were definitely related to the
      procedure were observed in ten patients (10%; peritonitis in six, acute
      cholecystitis in four). Of six patients with bile peritonitis, four suffered from
      mild localized peritonitis that improved with conservative treatment, whereas two
      developed pan-peritonitis that improved with additional intervention. Other three
      patients with a poor performance status succumbed shortly after the successful
      EUS-BD, with a possible association between the procedure and death. In the 68
      patients with a bilioenteric stent, the median time to recurrence of biliary
      obstruction was 339 days (95% confidence interval (CI), 14-664 days) during the
      mean follow-up period of 136 +/- 173 days. CONCLUSION: EUS-BD was found to be
      feasible. However, there were a few patients with an unfavorable course after
      successful EUS-BD.

PMID- 29656353
TI  - Adsorption of Cu (II) and Ni (II) from aqueous solutions by taro stalks
      chemically modified with diethylenetriamine.
AB  - Taro stalks (TS) were modified by diethylenetriamine (DETA) to obtain the
      modified taro stalks adsorbents (recorded as MTSA). This kind of raw material is
      unprecedented and the method of modification is relatively simple. The
      physicochemical properties of MTSA were characterized by scanning electron
      microscope (SEM), FTIR, and zeta potential analyzer. The capacity of MTSA for
      adsorbing heavy metals under different influencing factors was tested by UV
      visible spectrophotometer. The results indicated that the gaps between the
      microspheres of MTSA are more, which are conducive to adsorption. The MTSA might
      have increased the amino-functional groups which are beneficial for adsorption,
      resulting in an increase in the adsorption capacity of copper and nickel ions
      (35.71 and 31.06 mg/g) of about 5-7 times compared to bare taro stalks (5.27 mg/g
      and 6.08 mg/g). High Cu2+ uptake on MTSA was observed over the pH range of 5.5
      7.0, while for Ni2+ the range was 7.0-8.5, and the optimum dosage of adsorbent
      were both about 0.80 g for Cu2+ and Ni2+. The adsorption kinetics of Cu2+ and
      Ni2+ on MTSA could be interpreted with a pseudo-second order and the equilibrium
      data were best described by the Langmuir isotherm model. Graphical abstract ?.

PMID- 29656354
TI  - Distribution, relationship, and risk assessment of toxic heavy metals in walnuts
      and growth soil.
AB  - Walnut is one of the most popular nuts worldwide and contains various mineral
      nutrients. Little is known, however, about the relationship between toxic heavy
      metals in walnuts and growth soil. In this study, we investigated the
      distribution, relationship, and risk assessment of five toxic heavy metals-lead
      (Pb), arsenic (As), chromium (Cr), cadmium (Cd), and mercury (Hg)-in walnuts and
      growth soil in the main production areas of China. The results showed that the
      main heavy metal pollution in walnut and soil was Pb and Cd. Regionally, positive
      relationships existed between heavy metals and the pH and organic matter of soil.
      In addition, we observed a notable uptake effect between walnut and growth soil.
      In this study, we found a significant correlation (r = 0.786, P < 0.05) between
      the bioconcentration factors and the longitude of the sampling areas. The risks
      (total hazard quotients) of five heavy metals toward children and adults by
      dietary walnut consumption were 46.8 and 56.2%, respectively. The ability to
      identify toxic heavy metal pollution in walnuts and growth soil could be helpful
      to screen suitable planting sites to prevent and control heavy metal pollution
      and improve the quality and safety of walnut.

PMID- 29656355
TI  - NaCl impact on Kosteletzkya pentacarpos seedlings simultaneously exposed to
      cadmium and zinc toxicities.
AB  - Data regarding NaCl impact on halophyte plant species exposed to a polymetallic
      contamination remain scarce. Seedlings of the salt marsh species Kosteletzkya
      pentacarpos were simultaneously exposed to cadmium (10 MUM) and zinc (100 MUM) in
      the absence or presence of 50 mM NaCl. Heavy metal exposure reduced plant growth
      and increased Cd and Zn concentrations in all organs. Cd and Zn accumulation
      reduced net photosynthesis in relation to stomatal closure, decreased in
      chlorophyll concentration and alteration in chlorophyll fluorescence-related
      parameters. Salinity reduced Cd and Zn bioaccumulation and translocation, with a
      higher impact on Cd than Zn. It mitigated the deleterious impact of heavy metals
      on photosynthetic parameters. NaCl reduced the heavy metal-induced oxidative
      stress assessed by malondialdehyde, carbonyl, and H2O2 concentration. Subcellular
      distribution revealed that Cd mainly accumulated in the cell walls, but NaCl
      increased it in the cytosol fraction in the leaf and in the metal-rich granule
      fraction in the roots. It had no impact on Zn subcellular distribution. The
      additional NaCl contributed to a higher sequestration of Cd on phytochelatins and
      stimulated glutathione synthesis. The positive impact of NaCl on K. pentacarpos
      response to polymetallic pollution made this species a promising candidate for
      revegetation of heavy metal-contaminated salt areas.

PMID- 29656356
TI  - Performance of synthesized cast and electrospun PVA/chitosan/ZnO-NH2 nano
      adsorbents in single and simultaneous adsorption of cadmium and nickel ions from
      wastewater.
AB  - The performance of synthesized cast and electrospun polyvinyl
      alcohol/chitosan/zinc oxide/aminopropyltriethoxylsilane (PVA/chitosan/ZnO-APTES)
      nano-adsorbents were compared in removal of Cd(II) and Ni(II) ions from
      wastewater. The adsorbents were characterized by SEM, BET, FTIR and TGA analyses.
      Furthermore, the swelling investigations were carried out to study the adsorbent
      stability in aqueous solution. The effect of several parameters such as contents
      of ZnO-NH2, contact time, initial Cd(II) and Ni(II) concentration and temperature
      on the adsorption capacity was investigated in a batch mode. In comparison with
      cast adsorbent, nanofiber adsorbent indicated the better adsorption performance.
      The experimental data well fitted the double-exponential kinetic model. In single
      metal ion system, the maximum adsorption capacity of nanofiber for Cd(II) and
      Ni(II) ions is estimated to be 1.239 and 0.851 mmol/g, respectively, much higher
      than qm of cast adsorbent for Cd(II) (0.625 mmol/g) and Ni(II) (0.474 mmol/g)
      ions. Thermodynamic parameters were investigated to identify the nature of
      adsorption process. In binary system of Cd(II)-Ni(II) ions, the inhibitory effect
      of competitive Cd(II) ion on the Ni(II) adsorption was greater than the
      inhibitory effect of competitive on the Cd(II) adsorption. The selectivity
      adsorption of both nanofiber and cast adsorbents was in order of Cd(II) > Ni(II).

PMID- 29656357
TI  - Monitoring OH-PCBs in PCB transport worker's urine as a non-invasive exposure
      assessment tool.
AB  - In this study, we analyzed hydroxylated polychlorinated biphenyls (OH-PCBs) in
      urine of both PCB transport workers and PCB researchers. A method to monitor OH
      PCB in urine was developed. Urine was solid-phase extracted with 0.1% ammonia/
      methanol (v/v) and glucuronic acid/sulfate conjugates and then decomposed using
      beta-glucuronidase/arylsulfatase. After alkaline digestion/derivatization, the
      concentration of OH-PCBs was determined by HRGC/HRMS-SIM. In the first sampling
      campaign, the worker's OH-PCB levels increased several fold after the PCB waste
      transportation work, indicating exposure to PCBs. The concentration of OH-PCBs in
      PCB transport workers' urine (0.55~11 MUg/g creatinine (Cre)) was higher than in
      PCB researchers' urine (< 0.20 MUg/g Cre). However, also a slight increase of OH
      PCBs was observed in the researchers doing the air sampling at PCB storage area.
      In the second sampling, after recommended PCB exposure reduction measures had
      been enacted, the worker's PCB levels did not increase during handling of PCB
      equipment. This suggests that applied safety measures improved the situation.
      Hydroxylated trichlorobiphenyls (OH-TrCBs) were identified as a major homolog of
      OH-PCBs in urine. Also, hydroxylated tetrachlorobiphenyls (OH-TeCBs) to
      hydroxylated hexachlorobiphenyls (OH-HxCBs) were detected. For the sum of ten
      selected major indicators, a strong correlation to total OH-PCBs were found and
      these can possibly be used as non-invasive biomarkers of PCB exposure in workers
      managing PCB capacitors and transformer oils. We suggest that monitoring of OH
      PCBs in PCB management projects could be considered a non-invasive way to detect
      exposure. It could also be used as a tool to assess and improve PCB management.
      This is highly relevant considering the fact that in the next 10 years, approx.
      14 million tons of PCB waste need to be managed. Also, the selected populations
      could be screened to assess whether exposure at work, school, or home has taken
      place.

PMID- 29656358
TI  - A comparative study on defluoridation capabilities of biosorbents: isotherm,
      kinetics, thermodynamics, cost estimation, and eco-toxicological study.
AB  - The present study aims towards fluoride remediation from synthetic water using
      steam-activated carbon of Aegle marmelos (bael shell/wood apple) (BAC) and
      Parthenium hysterophorus (PHAC) according to batch sorption techniques. The
      impact of different parametric conditions viz. initial fluoride concentration (4
      12 mg/L), time (0-5 h), temperature (293.15-333.15 K), adsorbent dosage (4-14
      g/L), pH (4-9), and RPM (150-350) were considered for both the adsorbents.
      Maximum defluoridation of 89% was achieved by BAC at a concentration of 10 mg/L,
      adsorbent dose 6 g/L, pH 5, temperature 313.15 K, agitation speed 250 rpm, and
      contact time 9 h, whereas PHAC attained maximum removal of 78% at an initial
      concentration of 8 mg/L, adsorbent dose 10 g/L, pH 4, temperature 313.15 K, and
      contact time 12 h. Instrumental analysis by SEM, EDX, and FTIR confirmed about
      the fluoride binding ability of the adsorbents. The Langmuir isotherm model
      provided the best fit (R2 = 0.9962 and 0.9945) to the removal process with
      maximum adsorptive uptake of 16.85 and 6.22 mg/g by BAC and PHAC respectively.
      The adsorption phenomenon was found to obey pseudo-second-order kinetics. The
      endothermic, spontaneous, and feasible nature of the sorption process was
      confirmed by the thermodynamic study. The total costs of 1 kg adsorbent
      preparation were calculated as 1.122 USD and 1.0615 USD which helped us in
      determining the economic feasibility of the adsorbents in large-scale
      applications. The growth of Chlorella sorokiniana BTA 9031 was also observed to
      be affected by the fluoride solution. Comparing the removal efficiencies of both
      the adsorbents, it can be concluded that BAC shell proved to be an efficient
      adsorbent over PHAC for fluoride elimination from aqueous solution. Graphical
      abstract Defluoridation of aqueous solution using biochar derived from Aegle
      marmelos shell and Parthenium hysterophorus.

PMID- 29656359
TI  - Myocardial Infarct Size Reduction Provided by Local and Remote Ischaemic
      Preconditioning: References Values from the Hatter Cardiovascular Institute.
AB  - PURPOSE: To accurately estimate the effect size of both local or classic
      ischaemic preconditioning (IPC) and remote ischaemic preconditioning (RIPC) using
      a pooling data set of 91 animals. METHODS: We combined all the available mouse
      data collected from our Institute over the last 3 years regarding (i) local IPC
      (4 cycles of 5 min of global ischaemia/reperfusion injury, IRI, followed by 35
      min ischaemia and 2-h reperfusion) in the Langendorff-isolated perfused mouse
      heart model and (ii) RIPC (3 cycles of 5 min of limb occlusion followed by 40-min
      ischaemia and 2-h reperfusion) in the in vivo mouse model. RESULTS: Five
      independent experiments containing 27 control and 29 IPC mice were used to
      estimate the overall (i) local IPC effect, which reduced infarct size in the ex
      vivo setting by a mean difference of 24.1% (95% CI 19.5, 28.6%) when compared to
      untreated controls (P < 0.001) and for (ii) RIPC, three independent experiments
      including data for 16 control and 19 RIPC mice were used to estimate that RIPC
      diminished infarct size in the in-vivo setting by a mean difference of 20.8% (95%
      CI 14.7, 26.9%) when compared to controls (P < 0.001). CONCLUSIONS: Using a
      significant animal dataset, we found that local IPC reduces myocardial infarct
      size by 24.1% and RIPC by 20.8% in the ex vivo and in vivo mouse models of IRI,
      respectively. These differences may be used as reference values to either
      establish positive controls or to determine by how much myocardial infarct size
      can be reduced by novel cardioprotective interventions following an IRI insult.

PMID- 29656360
TI  - Dietary Vitamin E Status Dictates Oxidative Stress Outcomes by Modulating Effects
      of Fish Oil Supplementation in Alzheimer Disease Model APPswe/PS1dE9 Mice.
AB  - Quite a number of studies have examined the effects of fish oil supplementation
      on cognitive performance in different transgenic animal models of Alzheimer's
      disease (AD). However, inconsistent and controversial outcomes have been derived
      from these experiments. In order to investigate whether the beneficial effect of
      fish oil supplementation on cognition was dietary VE status associated, fish oil
      dietary intervention was carried out in transgenic APPswe/PS1dE9 (APP/PS1) mice.
      Control mice (C57BL/6J mice) were fed a normal control diet. APP/PS1 mice were
      assigned to a normal control diet group and low VE diet + fish oil supplement,
      normal VE diet + fish oil supplement, and high VE diet + fish oil supplement
      groups, respectively. After 7 months of dietary intervention, we found that fish
      oil supplementation improved behavioral performance, alleviated brain beta
      amyloid (Abeta) plaque burden, and attenuated the oxidative stress in APP/PS1
      mice by increasing cortical GSH content and total antioxidant capacity, as well
      as by decreasing MDA level. Fish oil treatment increased cortical n-3 PUFA
      concentration and decreased n-6/n-3 PUFA ratio in APP/PS1 mice. Fatty acid
      transporters, Nrf2 and downstream targets involved in cortical and hippocampal
      antioxidant system were also modulated by fish oil-supplemented diet. Our data
      demonstrate that fish oil supplementation exerts an enhanced modulatory effect on
      the antioxidant system and fatty acid concentrations in APP/PS1 mice fed on lowly
      or averagely concentrated level of VE-containing diet than in mice fed with VE
      rich diet. The current data do support previous findings that already dictate the
      beneficial effect of n-3 PUFAs on cognitive function. Moreover, the cognition
      promoting effects of n-3 PUFAs may be dietary VE status related.

PMID- 29656361
TI  - Characterization of the Mitochondrial Aerobic Metabolism in the Pre- and
      Perisynaptic Districts of the SOD1G93A Mouse Model of Amyotrophic Lateral
      Sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is an adult-onset fatal neurodegenerative
      disease characterized by muscle wasting, weakness, and spasticity due to a
      progressive degeneration of cortical, brainstem, and spinal motor neurons. The
      etiopathological causes are still largely obscure, although astrocytes definitely
      play a role in neuronal damage. Several mechanisms have been proposed to concur
      to neurodegeneration in ALS, including mitochondrial dysfunction. We have
      previously shown profound modifications of glutamate release and presynaptic
      plasticity in the spinal cord of the SOD1G93A mouse model of ALS. In this work,
      we characterized, for the first time, the aerobic metabolism in two specific
      compartments actively involved in neurotransmission (i.e. the presynaptic
      district, using purified synaptosomes, and the perisynaptic astrocyte processes,
      using purified gliosomes) in SOD1G93A mice at different stages of the disease.
      ATP/AMP ratio was lower in synaptosomes isolated from the spinal cord, but not
      from other brain areas, of SOD1G93A vs. control mice. The energy impairment was
      linked to altered oxidative phosphorylation (OxPhos) and increment of lipid
      peroxidation. These metabolic dysfunctions were present during disease
      progression, starting at the very pre-symptomatic stages, and did not depend on a
      different number of mitochondria or a different expression of OxPhos proteins.
      Conversely, gliosomes showed a reduction of the ATP/AMP ratio only at the late
      stages of the disease and an increment of oxidative stress also in the absence of
      a significant decrement in OxPhos activity. Data suggest that the presynaptic
      neuronal moiety plays a pivotal role for synaptic energy metabolism dysfunctions
      in ALS. Changes in the perisynaptic compartment seem subordinated to neuronal
      damage.

PMID- 29656362
TI  - Evaluation of Animal Models by Comparison with Human Late-Onset Alzheimer's
      Disease.
AB  - Despite many efforts to alleviate the pathological conditions of Alzheimer's
      disease (AD), effective therapeutic drugs have not been developed, mainly because
      of the lack of molecular information about AD and animal models. We observed the
      reciprocal regulation of AD-associated genes (AD genes) and their related
      functions. Upregulated AD genes were positioned in central regions in the protein
      protein interaction network and were involved in inflammation and DNA repair
      pathways. Downregulated AD genes positioned in the periphery of the network were
      associated with metabolic pathways. Using these features of AD genes, we found
      that 5*FAD, amyloid beta-injected mice, and rats in the initial phases after
      bilateral common carotid artery occlusion (BCCAO) exhibited patterns that were
      most similar to those of AD. In contrast, using differentially expressed genes
      from animal models, we observed that 3*Tg and animals in late phases of BCCAO
      were positioned close to AD genes.

PMID- 29656363
TI  - 2-Pentadecyl-2-Oxazoline Reduces Neuroinflammatory Environment in the MPTP Model
      of Parkinson Disease.
AB  - Current pharmacological management of Parkinson disease (PD) does not provide for
      disease modification, but addresses only symptomatic features. Here, we explore a
      new approach to neuroprotection based on the use of 2-pentadecyl-2-oxazoline (PEA
      OXA), the oxazoline derivative of the fatty acid amide signaling molecule
      palmitoylethanolamide (PEA), in an experimental model of PD. Daily oral treatment
      with PEA-OXA (10 mg/kg) significantly reduced behavioral impairments and neuronal
      cell degeneration of the dopaminergic tract induced by four intraperitoneal
      injections of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) on 8-week-old male C57 mice. Moreover, PEA-OXA
      treatment prevented dopamine depletion, increased tyrosine hydroxylase and
      dopamine transporter activities, and decreased alpha-synuclein aggregation in
      neurons. PEA-OXA treatment also diminished nuclear factor-kappaB traslocation,
      cyclooxygenase-2, and inducible nitric oxide synthase expression and through
      upregulation of the nuclear factor E2-related factor 2 pathway, induced
      activation of Mn-superoxide dismutase and heme oxygenase-1. Further, PEA-OXA
      modulated microglia and astrocyte activation and preserved microtubule-associated
      protein-2 alterations. In conclusion, pharmacological activation of nuclear
      factor E2-related factor 2 pathways with PEA-OXA may be effective in the future
      therapy of PD.

PMID- 29656364
TI  - Characteristic appearances of fundus autofluorescence in treatment-naive and
      active polypoidal choroidal vasculopathy: a retrospective study of 170 patients.
AB  - PURPOSE: To investigate the characteristic appearances of fundus autofluorescence
      (FAF) in patients with treatment-naive and active polypoidal choroidal
      vasculopathy (PCV). METHOD: Cases with the diagnosis of treatment-naive and
      active PCV from November 2012 to May 2017 at Peking Union Medical College
      Hospital were retrospectively reviewed. All patients underwent comprehensive
      ophthalmologic examination. Autofluorescence (AF) findings were described at the
      retinal sites of the corresponding lesions identified and diagnosed using
      indocyanine green angiography and spectral-domain optical coherence tomography.
      RESULTS: One hundred seventy patients with 192 affected eyes were included. The
      logMAR BCVA of the patients were 0.53 +/- 0.28. The six AF patterns of 243
      polypoidal lesions were confluent hypo-AF with hyper-AF ring (49.8%), confluent
      hypo-AF (22.6%), hyper-AF with hypo-AF ring (3.7%), granular hypo-AF (7.0%),
      blocked hypo-AF due to hemorrhage (8.6%), and polyps without apparent AF changes
      (8.2%). For 146 branching vascular networks (BVNs), 97.3% were granular hypo-AF,
      and others were blocked hypo-AF due to hemorrhage. CONCLUSION: In eyes with
      treatment-naive and active PCV, the polypoidal lesions and BVNs induce
      characteristic FAF changes. FAF images provide reliable adjunct reference for the
      diagnosis of PCV.

PMID- 29656365
TI  - Characterization of AAV vector particle stability at the single-capsid level.
AB  - Virus families have evolved different strategies for genome uncoating, which are
      also followed by recombinant vectors. Vectors derived from adeno-associated
      viruses (AAV) are considered as leading delivery tools for in vivo gene transfer,
      and in particular gene therapy. Using a combination of atomic force microscopy
      (AFM), biochemical experiments, and physical modeling, we investigated here the
      physical properties and stability of AAV vector particles. We first compared the
      morphological properties of AAV vectors derived from two different serotypes
      (AAV8 and AAV9). Furthermore, we triggered ssDNA uncoating by incubating vector
      particles to increasing controlled temperatures. Our analyses, performed at the
      single-particle level, indicate that genome release can occur in vitro via two
      alternative pathways: either the capsid remains intact and ejects linearly the
      ssDNA molecule, or the capsid is ruptured, leaving ssDNA in a compact entangled
      conformation. The analysis of the length distributions of ejected genomes further
      revealed a two-step ejection behavior. We propose a kinetic model aimed at
      quantitatively describing the evolution of capsids and genomes along the
      different pathways, as a function of time and temperature. This model allows
      quantifying the relative stability of AAV8 and AAV9 particles.

PMID- 29656366
TI  - Sodium selenite ameliorates both intestinal and extra-intestinal changes in
      acetic acid-induced colitis in rats.
AB  - Selenium and its derivatives including sodium selenite (sod sel) belong to the
      group of essential trace elements needed for proper health and nutrition. They
      are fairly safe and possess antioxidant and anti-inflammatory properties. The aim
      of present investigation was to elucidate the effect of sod sel on experimental
      colitis model in rats. Colitis was induced by intrarectal instillation of 4%
      (v/v) acetic acid. Two hours later, sod sel was given to rats on a daily basis
      for 15 consecutive days. Clinical symptoms, colon mass index, spleen weight
      inflammatory markers, hematological, biochemical, macroscopic, and histological
      changes were determined. Sod sel markedly ameliorated colitis as evidenced by a
      significant decrease in macroscopic and microscopic score, disease activity
      index, colon mass index, and spleen weight. Treatment with sod sel attenuated
      oxidative stress in the colon by normalizing the colonic content of nitric oxide,
      malondialdehyde, and reduced glutathione, as well as the activities of catalase,
      superoxide dismutase, and junctional adhesion molecule (JAM-a). In addition, it
      significantly reduced colonic myeloperoxidase content, the intercellular adhesion
      molecule (ICAM-1), and the proinflammatory cytokines; TNF-alpha, IL-1beta.
      Moreover, sod sel normalized hematological parameters, serum transaminases, and
      kidney and liver function enzymes. The current study indicates that sod sel was
      effective in ameliorating the intestinal and extra-intestinal manifestation in
      acetic acid-induced colitis through its antioxidant, anti-inflammatory, and
      immunomodulatory effects.

PMID- 29656367
TI  - The impact of coping patterns and chronic health conditions on health-related
      quality of life among children and adolescents.
AB  - : This study examined the relationship among chronic disease, coping strategy
      patterns, and health-related quality of life (HRQOL) among children and
      adolescents. The cohort included 273 Israeli children and adolescents aged 8-18
      years diagnosed with asthma, diabetes mellitus, or celiac disease. All completed
      the Coping with a Disease Questionnaire (CODI) and the DISABKIDS Chronic Generic
      Measure (DCGM-37). The outcome measures were as follows: association of the use
      of effective and non-effective coping strategies with type of disease; predictive
      value of coping patterns for health-related quality of life; a European sample
      was used for comparison. On k means cluster analysis, three strategy patterns
      (two "effective" and one "non-effective") were associated with health-related
      quality of life and disease specifics. Disease predicted coping patterns, but it
      had a weak direct relationship to health-related quality of life. Coping patterns
      were the strongest predictor of health-related quality of life. These results are
      similar to the European DISABKIDS study, indicating cross-cultural parallels.
      CONCLUSIONS: The findings highlight the power of the concept of coping patterns
      as opposed to coping strategies to explain HRQOL of children and adolescents with
      chronic disease. Both types of disease (categorical approach) and coping patterns
      (non-categorical approach) are relevant to predicting HRQOL. What is Known: * The
      literature on coping has widely documented the existence of individual (unique)
      coping strategies. * Coping strategies are considered "useful" or "non-useful,"
      based on whether they increase or decrease negative outcomes caused by certain
      stressors, such as chronic illness. What is New: * Our findings suggest that
      youngsters can use "non-useful" strategies to reduce stress caused by chronic
      illness, while still maintaining higher quality of life, as long as they also
      apply certain "useful" strategies. * The use of certain combinations of coping
      strategies, rather than single strategies, is more important to our understanding
      of how coping affects HRQOL of children with chronic disease.

PMID- 29656368
TI  - Fluorometric aptamer based assay for ochratoxin A based on the use of exonuclease
      III.
AB  - This study describes an aptamer based assay for the mycotoxin ochratoxin A (OTA).
      The method is based on the use of an OTA-specific aptamer, exonuclease (Exo) III,
      SYBR Gold as a fluorescent probe, and a complementary strand that specifically
      combines with the aptamer. In the presence of OTA, the aptamer and OTA hybridize,
      thereby resulting in the formation of ssDNA, which is not digested by Exo III.
      Intense fluorescence is observed after addition of SYBR Gold (best measured at
      excitation/emission wavelengths of 495/540 nm). Fluorescence increases linearly
      with the log of the OTA concentration in the range from 8 to 1000 ng.mL-1. The
      detection limit is 4.7 ng.mL-1. The assay was applied to the determination of OTA
      in diluted [2%(v/v)] red wine, and recoveries and RSDs ranged between 93.5% and
      113.8%, and between 3.2% and 5.7%, respectively. Graphical abstract In the
      presence of ochratoxin A (OTA), specific combinations of aptamer and OTA may
      occur and result in DNA double strands being untied, which avoids being digested
      by Exo III. Intense fluorescence is observed after SYBR Gold addition.

PMID- 29656369
TI  - Seeking for the Definition of "Culture": Current Concerns and their Implications.
      A Comment on Gustav Jahoda's Article "Critical Reflections on some Recent
      Definitions of "Culture'"'.
AB  - This article takes as a starting point the critical analysis of attempts to
      define "culture", offered by Jahoda in 2012. Basing on the observed proliferation
      of various, often contradicting, definitions of "culture" (for instance, trying
      to refer to its both internal and external aspects), Jahoda arrives at the
      conclusion that attempts to define the concept of "culture" are vain and useless
      and it is quite practicable simply to use the term without seeking to define it.
      We find it hard to agree with this statement. Elaborating on Jahoda reflections
      and drawing on the recent debates in social sciences, cultural studies and
      philosophy, we argue that seeking for the definition of culture is necessary in
      the context of contemporary development of social and humanitarian knowledge.
      Moreover, we claim that the debates about culture indicate the need for a large
      scale methodological reorganization of the social and humanitarian sciences, in
      response to the novel ontological congruence between internal and external, the
      fundamental "ontological shift", "reversing the poles" of the human-related
      reality. The human individual becomes its core element and pivot. Other
      "objects", "external" in relation to the individual (for instance, social
      structures and institutions), undergo such massive and rapid changes that grow
      progressively fuzzy and sometimes even less "real", comparing to the individual.
      The "inner" nature of the individual also transforms: from being "subjected" to
      think, act and feel according to certain external conditions, an individual
      becomes an Actor, who is empowered to change the environment following his
      purposive plans, desires and visions.

PMID- 29656371
TI  - Heavy metal bioaccumulation in Oreochromis niloticus from Tenango Dam, Puebla,
      Mexico.
AB  - Oreochromis niloticus was used to determine the effects of heavy metals and their
      concentration in aquatic environments. Its wide distribution, resistance, and
      economical importance make it a suitable biomonitor. The present study was
      conducted in the Tenango Dam (Puebla, Mexico) to determine water quality and its
      impact on O. niloticus, a species that is cultured and commercialized in this
      area. Five samples were collected over 1 year to evaluate the water's
      physicochemical parameters (temperature, dissolved oxygen, pH, and hardness) and
      metal contents (cadmium, chromium, copper, and lead). Metal concentrations,
      bioconcentration factors, and metallothionein levels were also assessed in O.
      niloticus livers and muscle tissues. Water and tilapia quality were estimated
      according to current Mexican guidelines. Results indicated that the water's
      physicochemical parameters were within acceptable ranges. Metal concentrations,
      however, suggested that this resource was not suitable for urban use. Moreover,
      metal levels in fish tissues exceeded the acceptable limits during two periods,
      rendering it unsuitable for human consumption. The bioconcentration factor
      indicated that the metals can potentially accumulate in organisms. Furthermore,
      metallothionein levels in liver and muscle showed a direct correlation with metal
      concentrations in these tissues. This is the first study to use tilapia as an
      indicator of contamination in the Tenango Dam, and also the first to describe the
      presence of metals in this water body.

PMID- 29656370
TI  - Role of Exosomes in Human Retroviral Mediated Disorders.
AB  - Retroviruses comprise an ancient and varied group of viruses with the unique
      ability to integrate DNA from an RNA transcript into the genome, a subset of
      which are able to integrate in humans. The timing of these integrations during
      human history has dictated whether these viruses have remained exogenous and
      given rise to various human diseases or have become inseparable from the host
      genome (endogenous retroviruses). Given the ability of retroviruses to integrate
      into the host and subsequently co-opt host cellular process for viral
      propagation, retroviruses have been shown to be closely associated with several
      cellular processes including exosome formation. Exosomes are 30-150 nm
      unilamellar extracellular vesicles that originate from intraluminal vesicles
      (ILVs) that form in the endosomal compartment. Exosomes have been shown to be
      important in intercellular communication and immune cell function. Almost every
      cell type studied has been shown to produce these types of vesicles, with the
      cell type dictating the contents, which include proteins, mRNA, and miRNAs.
      Importantly, recent evidence has shown that infection by viruses, including
      retroviruses, alter the contents and subsequent function of produced exosomes. In
      this review, we will discuss the important retroviruses associated with human
      health and disease. Furthermore, we will delve into the impact of exosome
      formation and manipulation by integrated retroviruses on human health, survival,
      and human retroviral disease pathogenesis.

PMID- 29656372
TI  - Serum calprotectin may reflect inflammatory activity in patients with active
      rheumatoid arthritis despite normal to low C-reactive protein.
AB  - Approximately half of patients with rheumatoid arthritis (RA) have normal C
      reactive protein (CRP) levels. Calprotectin is a promising and likely more
      specific biomarker of disease activity than conventionally used acute phase
      reactants. We aimed to analyse the levels of serum calprotectin in RA patients
      with clinically active disease and with normal/low CRP. A total of 160 RA
      patients underwent clinical examination (DAS28-ESR and CDAI). The levels of
      calprotectin were analysed in patients with moderate to high disease activity
      with normal/low CRP levels and in 32 healthy subjects. The discriminatory
      capacity of calprotectin to identify clinically active patients in spite of
      normal/low CRP was assessed using ROC curves. Out of all RA patients, 74/160
      (46.3%) were in remission or had low disease activity according to DAS28 and had
      normal/low CRP levels. However, 51/160 (32%) had normal/low CRP levels despite
      having moderate to high disease activity. In these patients, calprotectin levels
      were significantly higher than those in patients who had normal/low CRP and were
      in remission or showed low disease activity (2.7 +/- 1.5 vs. 2.1 +/- 1.2 MUg/mL,
      p = 0.043), which differed from those in healthy subjects (2.7 +/- 1.5 vs. 1.9 +/
      1.2 MUg/mL, p = 0.011). The discriminatory capacity for calprotectin to
      distinguish clinically active vs. inactive disease despite normal/low CRP using
      AUC of the DAS28 was 0.607 (95% CI 0.503 to 0.711, p = 0.043). The present study
      demonstrates that calprotectin may reflect inflammatory activity in RA patients
      where CRP fails to do so.

PMID- 29656373
TI  - Evaluation of disease activity in patients with rheumatoid arthritis treated with
      tofacitinib by RAPID3: post hoc analyses from two phase 3 trials.
AB  - Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid
      arthritis. We evaluated the relationship between disease activity, according to
      Routine Assessment of Patient Index Data 3 (RAPID3) after 6-month treatment with
      tofacitinib, and long-term outcomes at 24 months. This was a post hoc analysis of
      two 24-month, phase 3, randomized controlled trials in methotrexate (MTX)-naive
      (ORAL Start [NCT01039688]) or MTX-inadequate responder patients (ORAL Scan
      [NCT00847613]) receiving tofacitinib 5 or 10 mg twice daily (BID) as monotherapy
      or with background MTX. RAPID3 scores were calculated at baseline, month (M)6,
      and M24, and defined as remission (<= 3), low (LDA; > 3-<= 6), moderate (MDA; > 6
      <= 12), or high disease activity (HDA; > 12). Clinical Disease Activity Index
      (CDAI), Health Assessment Questionnaire-Disability Index (HAQ-DI) scores, and
      radiographic non-progression (modified Total Sharp Scores <= 0) at M24 were
      evaluated by M6 RAPID3 response. Among patients receiving tofacitinib 5 or 10 mg
      BID, respectively, 42.2 and 51.5% (ORAL Start) and 29.8 and 39.0% (ORAL Scan)
      achieved RAPID3 remission/LDA at M6. Most patients maintained/improved RAPID3
      responses at M24. A higher proportion of patients in RAPID3 remission/LDA versus
      MDA/HDA at M6 achieved CDAI remission, reported normative HAQ-DI scores (< 0.5),
      and achieved both normative HAQ-DI scores and radiographic non-progression at
      M24. Patients achieving RAPID3 remission/LDA after 6-month treatment with
      tofacitinib 5 or 10 mg BID have improved long-term outcomes versus patients with
      MDA/HDA. These findings support the use of RAPID3 to monitor longer-term disease
      activity in conjunction with physician-assessed measures.

PMID- 29656374
TI  - Expression of circulating Semaphorin3A and its association with inflammation and
      bone destruction in rheumatoid arthritis.
AB  - To determine the expression of Semaphorin3A (Sema3A) in rheumatoid arthritis (RA)
      patients, and analyze the correlation between serum Sema3A and the pathogenesis
      of RA. The concentration of serum Sema3A and its mRNA expression level were
      detected in RA patients. The association of serum Sema3A level with clinical and
      laboratory features of RA were analyzed. Serum Sema3A of 130 RA patients (15.89
      +/- 8.58 ng/ml) was significantly higher than that of 150 HC (6.96 +/- 2.62
      ng/ml) and 215 patients with other rheumatic diseases (P < 0.05). Consistent with
      the serum level, the Sema3A mRNA level was also higher in RA patients' PBMC than
      that in HC (1.8-fold increase, P < 0.01). The serum level of Sema3A was
      correlated with platelet counts (r = 0.229), ESR (r = 0.172), RF (r = 0.230), IgM
      (r = 0.254) and Sharp score (r = 0.254), and bone mineral density (BMD) of lumbar
      spine (r = 0.263). Serum Sema3A was also fundamentally higher in AKA-, APF-, anti
      CCP-positive groups compared with negative groups (P < 0.05). The ROC curve
      showed that the optimum diagnostic cutoff value for Sema3A was 10.881 ng/ml. RF
      level and antibodies (anti-CCP, APF, AKA, and GPI) positive rates were
      significantly higher in Sema3A positive group. Sharp score was also higher,
      although without significance. The expression of Sema3A is significantly elevated
      in RA patients. The level of serum Sema3A is positively correlated with
      inflammatory factors (including ESR, IgM, and RF) and is associated with auto
      antibody production and bone destruction.

PMID- 29656375
TI  - Does erythrocyte sedimentation rate reflect and discriminate flare from infection
      in systemic lupus erythematosus? Correlation with clinical and laboratory
      parameters of disease activity.
AB  - To examine disease activity parameters in patients with systemic lupus
      erythematosus (SLE) experiencing flare, infection, both, or neither condition,
      focusing on erythrocyte sedimentation rate (ESR). This study is a retrospective
      analysis of 371 consecutive inpatient SLE cases from 2006 to 2015. Cases were
      classified as flare (n = 147), infection (n = 48), both (n = 23), or neither (n =
      135). ESR levels were correlated to C-reactive protein (CRP), ferritin, anti
      dsDNA antibodies, complement C3 reduction, serositis, and erythrocyturia with
      proteinuria (Pearson's correlation). ESR levels were related to an age- and
      gender-adapted cut-off value (ESRp). We analyzed mean values of age, ESR, ESRp,
      CRP, ferritin and distribution of anti-dsDNA antibodies, C3 reduction, serositis,
      and erythrocyturia with proteinuria. Sensitivity and specificity were calculated
      via receiver operating characteristic or two-by-two table. Association of
      parameters with disease activity and infection was tested via two-sided chi
      square test. ESR correlated moderately with CRP in cases with flare and/or
      infection (r = 0.505-0.586). While ESR and CRP were normal in remission, mean
      values overlapped in cases with flare, infection, or both. ESRp was higher in
      flare than in infection (p = 0.048). ESR lost association to activity in infected
      cases, CRP to infection in flaring cases. ESRp, serositis, and anti-dsDNA
      antibodies were related to disease activity regardless of infections. Anti-dsDNA
      antibodies were most sensitive for detecting flares (74%), while serositis,
      proteinuria with erythrocyturia, anti-dsDNA antibodies, C3 reduction, and ESRp
      values >= 2 were most specific. ESR levels were raised by flares, infections, and
      age; adapting them to age and gender increased their diagnostic value. Obtaining
      several parameters remains necessary to differentiate flare from infection.

PMID- 29656377
TI  - Are CT-Based Finite Element Model Predictions of Femoral Bone Strengthening
      Clinically Useful?
AB  - PURPOSE OF REVIEW: This study reviews the available literature to compare the
      accuracy of areal bone mineral density derived from dual X-ray absorptiometry
      (DXA-aBMD) and of subject-specific finite element models derived from
      quantitative computed tomography (QCT-SSFE) in predicting bone strength measured
      experimentally on cadaver bones, as well as their clinical accuracy both in terms
      of discrimination and prediction. Based on this information, some basic cost
      effectiveness calculations are performed to explore the use of QCT-SSFE instead
      of DXA-aBMD in (a) clinical studies with femoral strength as endpoint, (b)
      predictor of the risk of hip fracture in low bone mass patients. RECENT FINDINGS:
      Recent improvements involving the use of smooth-boundary meshes, better
      anatomical referencing for proximal-only scans, multiple side-fall directions,
      and refined boundary conditions increase the predictive accuracy of QCT-SSFE. If
      these improvements are adopted, QCT-SSFE is always preferable over DXA-aBMD in
      clinical studies with femoral strength as the endpoint, while it is not yet cost
      effective as a hip fracture risk predictor, although pathways that combine both
      QCT-SSFE and DXA-aBMD are promising.

PMID- 29656378
TI  - Exopolysaccharides from Lactobacillus plantarum induce biochemical and
      physiological alterations in tomato plant against bacterial spot.
AB  - This study aimed to evaluate the effectiveness of exopolysaccharides (EPS)
      produced by Lactobacillus plantarum in controlling bacterial spot and eliciting
      defense mechanisms, and verify alterations in the tomato plant physiological
      responses. Tomato plants with five definitive leaves were sprayed with EPS,
      acibenzolar-S-methyl (ASM, positive control), or distilled water (negative
      control) and inoculated with Xanthomonas gardneri after 3 days. Local and
      systemic protection was evaluated 7, 15, and 21 days after inoculation.
      Biochemical defense mechanisms (peroxidases [POX], polyphenoloxidases [PPO],
      catalase [CAT], superoxide dismutase [SOD], accumulation of hydrogen peroxide
      [H2O2], and physiological changes) were quantified. In addition, histochemical
      analyses were examined through light and fluorescence microscopy in treated
      tomato plants, inoculated or not with X. gardneri. On average, EPS and ASM
      provided 55 and 96% reduction, respectively, of the bacteriosis severity in
      treated leaves, compared to the control plants. Increased activities of PPO, CAT,
      and SOD were found in the EPS-treated plants after being challenged with the
      pathogen. ASM caused increases in all enzymes analyzed, especially in inoculated
      plants. The rate of photosynthesis was three times higher, while stomatal
      conductance and transpiration were 36% lower in the plants sprayed with EPS and
      challenged with the pathogen, compared to the inoculated control plants. The
      photochemical efficiency and Soil Plant Analysis Development (SPAD) index did not
      change. Under light and fluorescence microscopy, it could be seen accumulation of
      cellulosic compounds in the epidermis of the leaves treated with EPS. Therefore,
      application of EPS can be considered an alternative for the control of bacterial
      spot in tomato plants. The study discusses how biochemical and physiological
      alterations caused by the polysaccharide in the plants contributed to reduce the
      severity of the disease.

PMID- 29656376
TI  - Human Genetics of Sclerosing Bone Disorders.
AB  - PURPOSE OF REVIEW: The group of sclerosing bone disorders encompasses a variety
      of disorders all marked by increased bone mass. In this review, we give an
      overview of the genetic causes of this heterogeneous group of disorders and
      briefly touch upon the value of these findings for the development of novel
      therapeutic agents. RECENT FINDINGS: Advances in the next-generation sequencing
      technologies are accelerating the molecular dissection of the pathogenic
      mechanisms underlying skeletal dysplasias. Throughout the years, the genetic
      cause of these disorders has been extensively studied which resulted in the
      identification of a variety of disease-causing genes and pathways that are
      involved in bone formation by osteoblasts, bone resorption by osteoclasts, or
      both processes. Due to this rapidly increasing knowledge, the insights into the
      regulatory mechanisms of bone metabolism are continuously improving resulting in
      the identification of novel therapeutic targets for disorders with reduced bone
      mass and increased bone fragility.

PMID- 29656379
TI  - Cross-cultural adaptation and psychometric properties of the SCOPA-Sleep-German
      version.
AB  - Aim of the study was the cross-cultural adaptation and validation of the German
      version of the Scale for Outcomes in Parkinson's disease-Sleep Scale (SCOPA
      Sleep) for assessment of night-time sleep problems (NS) and daytime sleepiness
      (DS). Eighty-three patients with Parkinson's disease completed the SCOPA-Sleep
      and a multitude of measures for assessment of validity (e.g., PSQI, ESS). Twenty
      patients completed the SCOPA-Sleep twice within 2 months for assessment of retest
      reliability. Sixty-four healthy controls were also included for validity
      estimation. Internal consistency (Cronbach's alpha) was good with coefficients of
      .801 and .854 for SCOPA-NS and SCOPA-DS, respectively. Test-retest reliability
      and inter-rater agreement were excellent. Factor analysis revealed two factors,
      one for each of the subscales NS and DS. Convergent validity was high with
      correlations of .797 between SCOPA-NS and PSQI, and .679 between SCOPA-DS and
      ESS. The German version of the SCOPA-Sleep showed good diagnostic accuracy.
      Optimal cutoff scores were calculated, resulting in an AUC of .908 for NS and of
      .959 for DS. The German version of the SCOPA-Sleep is a reliable and valid
      instrument for assessing NS and DS in patients with Parkinson's disease. As
      diagnostic accuracy is excellent, this scale can be recommended for routine
      assessment of both NS and DS in PD combined with other standard measures.

PMID- 29656380
TI  - Trends in use of lymphadenectomy in surgery with curative intent for intrahepatic
      cholangiocarcinoma.
AB  - BACKGROUND: The role of routine lymph node dissection (LND) in the surgical
      treatment of intrahepatic cholangiocarcinoma (ICC) remains controversial. The
      objective of this study was to investigate the trends of LND use in the surgical
      treatment of ICC. METHODS: Patients undergoing curative intent resection for ICC
      in 2000-2015 were identified from an international multi-institutional database.
      Use of lymphadenectomy was evaluated over time and by geographical region (West
      versus East); LND use and final nodal status were analysed relative to AJCC T
      categories. RESULTS: Among the 1084 patients identified, half (535, 49.4 per
      cent) underwent concomitant hepatic resection and LND. Between 2000 and 2015, the
      proportion of patients undergoing LND for ICC nearly doubled: 44.4 per cent in
      2000 versus 81.5 per cent in 2015 (P < 0.001). Use of LND increased over time
      among both Eastern and Western centres. The odds of LND was associated with the
      time period of surgery and the extent of the tumour/T status (referent T1a: OR
      2.43 for T2, P = 0.001; OR 2.13 for T3, P = 0.016). Among the 535 patients who
      had LND, lymph node metastasis (LNM) was noted in 209 (39.1 per cent).
      Specifically, the incidence of LNM was 24 per cent in T1a disease, 22 per cent in
      T1b, 42.9 per cent in T2, 48 per cent in T3 and 66 per cent in T4 (P < 0.001).
      AJCC T3 and T4 categories, harvesting of six or more lymph nodes, and presence of
      satellite lesions were independently associated with LNM. CONCLUSION: The rate of
      LNM was high across all T categories, with one in five patients with T1 disease
      having nodal metastasis. The trend in increased use of LND suggests a growing
      adoption of AJCC recommendations in the treatment of ICC.

PMID- 29656381
TI  - Cowpea: an overview on its nutritional facts and health benefits.
AB  - Cowpea (Vigna unguiculata) is a legume consumed as a high-quality plant protein
      source in many parts of the world. High protein and carbohydrate contents with a
      relatively low fat content and a complementary amino acid pattern to that of
      cereal grains make cowpea an important nutritional food in the human diet. Cowpea
      has gained more attention recently from consumers and researchers worldwide as a
      result of its exerted health beneficial properties, including anti-diabetic, anti
      cancer, anti-hyperlipidemic, anti-inflammatory and anti-hypertensive properties.
      Among the mechanisms that have been proposed in the prevention of chronic
      diseases, the most proven are attributed to the presence of compounds such as
      soluble and insoluble dietary fiber, phytochemicals, and proteins and peptides in
      cowpea. However, studies on the anti-cancer and anti-inflammatory properties of
      cowpea have produced conflicting results. Some studies support a protective
      effect of cowpea on the progression of cancer and inflammation, whereas others
      did not reveal any. Because there are only a few studies addressing health
      related effects of cowpea consumption, further studies in this area are
      suggested. In addition, despite the reported favorable effects of cowpea on
      diabetes, hyperlipidemia and hypertension, a long-term epidemiological study
      investigating the association between cowpea consumption and diabetes,
      cardiovascular disease and cancer is also recommended. (c) 2018 Society of
      Chemical Industry.

PMID- 29656382
TI  - Opioid Prescriptions in Older Medicare Beneficiaries After the 2014 Federal
      Rescheduling of Hydrocodone Products.
AB  - OBJECTIVES: To examine how an October 2014 Drug Enforcement Administration policy
      reclassified hydrocodone product from schedule III to II has affected older
      adults, who are among the largest consumers of prescription opioids in the United
      States. DESIGN: Retrospective cohort study. SETTING: United States. PARTICIPANTS:
      A 20% sample of Medicare Part D beneficiaries aged 65 and older from 2013 through
      2015 (> 2,500,000 beneficiaries each year) MEASUREMENTS: From January 2013 to
      December 2015, we calculated the monthly prevalence of opioid prescriptions and
      the prevalence of individuals who received prescriptions for a 90-day supply or
      longer (prolonged), as well as hospitalizations related to opioid toxicity in
      2013 and 2015. RESULTS: From 2013 to 2015, the proportion of Medicare Part D
      enrollees who received a hydrocodone prescription in a year decreased from 21.9%
      to 18.3%. Monthly rates for hydrocodone prescriptions declined significantly in
      2014. The risk of receiving prolonged opioid prescriptions decreased by
      approximately 7% in the multivariable analyses comparing 2015 to 2013 (prevalence
      ratio=0.93, 95% confidence interval (CI)=0.93-0.94). Medicare enrollees with an
      original entitlement because of disability or with Medicaid eligibility had
      smaller decreases in prolonged prescriptions and, unexpectedly, small increases
      in high-dose prescriptions. Opioid-related hospitalizations did not change
      significantly, but opioid-related hospitalizations without a documented opioid
      prescription increased (odds ratio=1.24, 95% CI=1.03-1.50). CONCLUSION: The 2014
      change in hydrocodone from schedule III to schedule II was associated with modest
      decreases in rates of opioid use in the elderly. The unexpected increase in
      opioid-related hospitalizations without documented opioid prescriptions may
      represent an increase in illegal use.

PMID- 29656383
TI  - Improved Method for Estimating Reaction Rates During Push-Pull Tests.
AB  - The breakthrough curve obtained from a single-well push-pull test can be adjusted
      to account for dilution of the injection fluid in the aquifer fluid. The dilution
      adjusted breakthrough curve can be analyzed to estimate the reaction rate of a
      solute. The conventional dilution-adjusted method assumes that the ratios of the
      concentrations of the nonreactive and reactive solutes in the injection fluid vs.
      the aquifer fluid are equal. If this assumption is invalid, the conventional
      method will generate inaccurate breakthrough curves and may lead to erroneous
      conclusions regarding the reactivity of a solute. In this study, a new method
      that generates a dilution-adjusted breakthrough curve was theoretically developed
      to account for any possible combination of nonreactive and reactive solute
      concentrations in the injection and aquifer fluids. The newly developed method
      was applied to a field-based data set and was shown to generate more accurate
      dilution-adjusted breakthrough curves. The improved dilution-adjusted method
      presented here is simple, makes no assumptions regarding the concentrations of
      the nonreactive and reactive solutes in the injection and aquifer fluids, and
      easily allows for estimating reaction rates during push-pull tests.

PMID- 29656384
TI  - Supporting Mentoring Relationships of Youth in Foster Care: Do Program Practices
      Predict Match Length?
AB  - Implementation of research- and safety-based program practices enhance the
      longevity of mentoring relationships, in general; however, little is known about
      how mentoring programs might support the relationships of mentees in foster care.
      Benchmark program practices and Standards in the Elements of Effective Practice
      for Mentoring, 3rd Edition (MENTOR, 2009) were assessed in the current study as
      predictors of match longevity. Secondary data analyses were conducted on a
      national agency information management database from 216 Big Brothers Big Sisters
      agencies serving 641 youth in foster care and 70,067 youth not in care from
      across the United States (Mean = 11.59 years old at the beginning of their
      matches) in one-to-one, community-based (55.06%) and school- or site-based
      (44.94%) matches. Mentees in foster care had shorter matches and matches that
      were more likely to close prematurely than mentees who were not in foster care.
      Agency leaders from 32 programs completed a web-based survey describing their
      policies and practices. The sum total numbers of Benchmark program practices and
      Standards were associated with match length for 208 mentees in foster care;
      however, neither predicted premature match closure. Results are discussed in
      terms of how mentoring programs and their staff can support the mentoring
      relationships of high-risk youth in foster care.

PMID- 29656385
TI  - Improving the lipid profile of ready-to-cook meat products by addition of omega-3
      microcapsules: effect on oxidation and sensory analysis.
AB  - BACKGROUND: The omega-3 enrichment of ready-to-cook meat products by
      microencapsulated fish oil (MFO) addition was analyzed. Accordingly, three
      batches of chicken nuggets were prepared: (i) control (C); (ii) enriched in bulk
      fish oil (BFO); and (iii) with added MFO. Sensory features, acceptability,
      oxidative stability and volatile compounds were analyzed. RESULTS: MFO nuggets
      did not differ from C ones with respect to any sensory trait. BFO showed
      increased juiciness and saltiness but decreased meat flavor. Acceptability was
      not affected by enrichment. Consumers were not able to differentiate between C
      and MFO in a triangle test, although they could clearly identify BFO nuggets.
      Higher levels of lipid and protein oxidation indicators and of volatile compounds
      from fatty acid oxidation were found in BFO nuggets compared to C and MFO
      nuggets. CONCLUSION: Enrichment of ready-to-cook meat products in omega-3 fatty
      acids with MFO provides both lipid and protein oxidative protection without
      changes in sensory quality. (c) 2018 Society of Chemical Industry.

PMID- 29656386
TI  - The Eating and Drinking Ability Classification System: concurrent validity and
      reliability in children with cerebral palsy.
AB  - AIM: As there is little evidence for concurrent validity of the Eating and
      Drinking Ability Classification System (EDACS), this study aimed to determine its
      concurrent validity and reliability in children and adolescents with cerebral
      palsy (CP). METHOD: After an extensive translation procedure, we applied the
      German language version to 52 participants with CP (30 males, 22 females, mean
      age 9y 7mo [SD 4y 2mo]). We correlated (Kendall's tau or Ktau ) the EDACS levels
      with the Bogenhausener Dysphagiescore (BODS), and the EDACS level of assistance
      with the Manual Ability Classification System (MACS) and the item 'eating' of the
      Functional Independence Measure for Children (WeeFIM). We further quantified the
      interrater reliability between speech and language therapists (SaLTs) and between
      SaLTs and parents with Kappa (kappa). RESULTS: The EDACS levels correlated highly
      with the BODS (Ktau =0.79), and the EDACS level of assistance correlated highly
      with the MACS (Ktau =0.73) and WeeFIM eating item (Ktau =-0.80). Interrater
      reliability proved almost perfect between SaLTs (EDACS: kappa=0.94; EDACS level
      of assistance: kappa=0.89) and SaLTs and parents (EDACS: kappa=0.82; EDACS level
      of assistance: kappa=0.89). INTERPRETATION: The EDACS levels and level of
      assistance seem valid and showed almost perfect interrater reliability when
      classifying eating and drinking problems in children and adolescents with CP.
      WHAT THIS PAPER ADDS: The Eating and Drinking Ability Classification System
      (EDACS) correlates well with a dysphagia score. The EDACS level of assistance
      proves valid. The German version of EDACS is highly reliable. EDACS correlates
      moderately to highly with other classification systems.

PMID- 29656387
TI  - A nationwide analysis of 30-day adverse events, unplanned readmission, and length
      of hospital stay after peripheral nerve surgery in extremities and the brachial
      plexus.
AB  - BACKGROUND: Little is known on adverse events and their timing after peripheral
      nerve surgery in extremities. The aim of this study is to identify predictors and
      typical timing of complications, unplanned readmission, and length of hospital
      stay for patients undergoing peripheral nerve surgery in the extremities.
      METHODS: Data were extracted from the National Surgical Quality Improvement
      Program (NSQIP) registry from 2005 to 2015. Adult patients undergoing peripheral
      nerve surgery in the extremities were included. A subgroup analysis was performed
      for brachial plexus operations. Multivariable logistic regression was performed
      to identify predictors of any complication, surgical site infection, unplanned
      readmission, and reoperation. RESULTS: A total of 2,840 patients were identified;
      628 were brachial plexus operations. Overall complications were 4.4% and 7.0%,
      respectively. Median time for occurrence of any complication was 8 days. The most
      common complications were wound-related (1.7%), which occurred at a median of 15
      days postoperatively. Reoperation occurred in 1.8% of all cases; most commonly
      for musculoskeletal repair (16.7%). Unplanned readmissions occurred in 2.3% and
      were most often due to wound-related problems (24.1%). Preoperatively
      contaminated wounds, inpatient procedures, and longer operative time seemed to
      have the most influence on all adverse events. In brachial plexus pathology,
      insulin-dependent diabetes and emergency cases also negatively affected outcomes.
      CONCLUSIONS: Complications usually occur one to two weeks postoperatively.
      Preoperatively contaminated wounds, inpatient procedures, and longer operative
      times influence outcome. Anatomical level of operation results in significantly
      different lengths of hospital stay; brachial plexus pathology has the longest
      length of stay.

PMID- 29656388
TI  - Preliminary Results of Acoustic Radiation Force Impulse Imaging by Combined
      Qualitative and Quantitative Analyses for Evaluation of Breast Lesions.
AB  - OBJECTIVES: The purpose of this study was to evaluate the application of a new
      elastographic technique, acoustic radiation force impulse (ARFI) imaging, and its
      diagnostic performance for characterizing breast lesions. METHODS: One hundred
      consecutive female patients with 126 breast lesions were enrolled in our study.
      After routine breast ultrasound examinations, the patients underwent ARFI
      elasticity imaging. Virtual Touch tissue imaging (VTI) and Virtual Touch tissue
      quantification (Siemens Medical Solutions, Mountain View, CA) were used to
      qualitatively and quantitatively analyze the elasticity and hardness of tumors. A
      receiver operating characteristic curve analysis was performed to evaluate the
      diagnostic performance of ARFI for discrimination between benign and malignant
      breast lesions. RESULTS: Pathologic analysis revealed 40 lesions in the malignant
      group and 86 lesions in the benign group. Different VTI patterns were observed in
      benign and malignant breast lesions. Eighty lesions (93.0%) of benign group had
      pattern 1, 2, or 3, whereas all pattern 4b lesions (n = 20 [50.0%]) were
      malignant. Regarding the quantitative analysis, the mean VTI-to-B-mode area
      ratio, internal shear wave velocity, and marginal shear wave velocity of benign
      lesions were statistically significantly lower than those of malignant lesions
      (all P < .001). The cutoff point for a scoring system constructed to evaluate the
      diagnostic performance of ARFI was estimated to be between 3 and 4 points for
      malignancy, with sensitivity of 77.5%, specificity of 96.5%, accuracy of 90.5%,
      and an area under the curve of 0.933. CONCLUSIONS: The application of ARFI
      technology has shown promising results by noninvasively providing substantial
      complementary information and could potentially serve as an effective diagnostic
      tool for differentiation between benign and malignant breast lesions.

PMID- 29656389
TI  - The robustness of T2 value as a trabecular structural index at multiple spatial
      resolutions of 7 Tesla MRI.
AB  - PURPOSE: To evaluate the robustness of MR transverse relaxation times of
      trabecular bone from spin-echo and gradient-echo acquisitions at multiple spatial
      resolutions of 7 T. METHODS: The effects of MRI resolutions to T2 and T2* of
      trabecular bone were numerically evaluated by Monte Carlo simulations. T2 , T2*,
      and trabecular structural indices from multislice multi-echo and UTE acquisitions
      were measured in defatted human distal femoral condyles on a 7 T scanner.
      Reference structural indices were extracted from high-resolution microcomputed
      tomography images. For bovine knee trabecular samples with intact bone marrow, T2
      and T2* were measured by degrading spatial resolutions on a 7 T system. RESULTS:
      In the defatted trabecular experiment, both T2 and T2* values showed strong ( |r|
      > 0.80) correlations with trabecular spacing and number, at a high spatial
      resolution of 125 um3 . The correlations for MR image-segmentation-derived
      structural indices were significantly degraded ( |r| < 0.50) at spatial
      resolutions of 250 and 500 um3 . The correlations for T2* rapidly dropped ( |r| <
      0.50) at a spatial resolution of 500 um3 , whereas those for T2 remained
      consistently high ( |r| > 0.85). In the bovine trabecular experiments with intact
      marrow, low-resolution (approximately 1 mm3 , 2 minutes) T2 values did not
      shorten ( |r| > 0.95 with respect to approximately 0.4 mm3 , 11 minutes) and
      maintained consistent correlations ( |r| > 0.70) with respect to trabecular
      spacing (turbo spin echo, 22.5 minutes). CONCLUSION: T2 measurements of
      trabeculae at 7 T are robust with degrading spatial resolution and may be
      preferable in assessing trabecular spacing index with reduced scan time, when
      high-resolution 3D micro-MRI is difficult to obtain.

PMID- 29656390
TI  - Documenting the Growth of Ultrasound Research in Emergency Medicine Through a
      Bibliometric Analysis of Accepted Academic Conference Abstracts.
AB  - OBJECTIVES: Ultrasound (US) has become an indispensable skill for emergency
      physicians. Growth in the use of US in emergency medicine (EM) has been
      characterized by practice guidelines, education requirements, and the number of
      EM US practitioners. Our purpose was to further document the growth of EM US by
      profiling the breadth, depth, and quality of US-related research presented at
      EM's most prominent annual research conference: the Society for Academic
      Emergency Medicine Annual Meeting. METHODS: We reviewed published research
      abstracts from the annual Society for Academic Emergency Medicine conferences
      from 1999 to 2015. Abstracts related to US were identified and examined for the
      number of authors and rigor of the research design. Designs were categorized as
      experimental, quasiexperimental, and nonexperimental. Abstract submissions were
      analyzed by the average rate of change over time. RESULTS: From 1999 to 2015, we
      observed a 10.2% increase in the number of accepted abstracts related to US
      research. This rate compared to a 3.2% average rate of change for all abstracts
      in general. The number of unique authors engaged in US research increased at a
      rate of 26.6%. Of the 602 abstracts identified as US related, only 12% could be
      considered experimental research. CONCLUSIONS: We observed larger increases in
      the number of US-related research relative to the total number of abstracts
      presented at a national conference. The number of investigators engaging in this
      research has also steadily increased. The research design of these studies was
      found to be primarily quasiexperimental. To improve the quality of EM's use of
      point-of-care US, more rigorous research with experimental designs is needed.

PMID- 29656391
TI  - Proteomic analysis of sperm proteins in infertile men with high levels of
      reactive oxygen species.
AB  - Oxidative stress is a significant risk factor for male infertility. A pro-oxidant
      testicular environment may alter the expression profile of functional sperm
      proteins and result in poor sperm quality. Patients and donors were divided into
      ROS (-) and ROS (+) groups. Using computational studies, and data mining of
      available literature on spermatozoa, oxidative stress and proteomics, we
      identified three core regulatory proteins angiotensin-converting enzyme (ACE),
      heat-shock protein (Hsp70) family A member 2 (HSPA2) and ribosomal protein
      subunit 27A (RPS27A) and seven interlink proteins NOS2, SUMO2, UBL4A, FBXO25,
      MAP3K3, APP and UBC. HSPA2 was validated by Western Blot, while the localisation
      of ACE, RPS27A, MAP3K3 and APP was identified by immunocytochemistry. The
      obtained results showed that HSPA2 was 1.2 (ROS+) and 2.1 (ROS-) fold
      downregulated in spermatozoa from patients with high levels of reactive oxygen
      species (ROS). ACE and APP were localised in the post-acrosomal region of
      spermatozoa, whereas RPS27A and MAP3K3 were localised either in the tail or sperm
      neck area. Our data show that these proteins may play a role in ROS-induced male
      infertility.

PMID- 29656392
TI  - Epigenetic modifications preserve the hyperaccumulator Noccaea caerulescens from
      Ni geno-toxicity.
AB  - The Ni hyperaccumulator Noccaea caerulescens has adapted to live in a naturally
      stressed environment, evolving a complex pattern of traits to cope with adverse
      conditions. Evidence is accumulating regarding the important role of epigenetic
      modifications in regulating plant responses to stress. In this study, we present
      data from the natural "open-field" adaptation of the Ni hyperaccumulator N.
      caerulescens to serpentine soil and provide the first evidence of the involvement
      of epigenetic changes in response to the high Ni content present in plant leaves.
      The alkaline comet assay revealed the integrity of the nuclei of leaf cells of N.
      caerulescens grown in a Ni-rich environment, while in the non-tolerant
      Arabidopsis thaliana exposed to Ni, the nuclei were severely damaged. DNA of N.
      caerulescens plants grown in situ were considerably hyper-methylated compared to
      A. thaliana plants exposed to Ni. In addition, qRT-PCR revealed that N.
      caerulescens MET1, DRM2, and HDA8 genes involved in epigenetic DNA and histone
      modification were up-regulated in the presence of high Ni content in leaves. Such
      epigenetic modifications may constitute a defense strategy that prevents genome
      instability and direct damage to the DNA structure by Ni ion, enabling plants to
      survive in an extreme environment. Further studies will be necessary to analyze
      in detail the involvement of DNA methylation and other epigenetic mechanisms in
      the complex process of metal hyperaccumulation and plants' adaptive response.
      Environ. Mol. Mutagen. 59:464-475, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29656393
TI  - Editorial: Cancer, drugs, and bugs-Bacteriotherapy on the rise?
AB  - Discussion on how the gut microbiota orchestrates immune responses during cancer
      therapies and how targeting the microbiota can prevent chemotherapy-induced
      toxicity.

PMID- 29656398
TI  - Impact of prolonged dialysis prior to renal transplantation.
AB  - INTRODUCTION: The new kidney allocation system (KAS) prioritizes patients based
      on date of dialysis initiation or waitlisting, whichever is earlier. We
      hypothesized that this change would increase transplant rates for patients with
      prolonged pretransplant dialysis times (DT) and aimed to assess the impact of
      prolonged DT on post-transplant outcomes. METHODS: We used United Network for
      Organ Sharing registry data to assess outcomes for patients added to the renal
      transplant waitlist from January 1, 1998 to December 31, 2010 and patients
      transplanted from January 1, 1998 to December 3, 2012. RESULTS: Compared with
      patients transplanted pre-emptively, patients with <5 years, 5-9 years, and >=10
      years DT had progressively decreased graft and patient survival (P < .001). The
      rates of short-term complications including delayed graft function, graft loss
      within 30 days, and patient death within 30 days were significantly higher in
      cohorts with >=10 years DT than in cohorts with less DT (P < .001). CONCLUSIONS:
      Patients with pretransplant DT of >=10 years had worse outcomes than patients pre
      emptively transplanted or transplanted with shorter DT. Durations of dialysis
      dependence beyond 10 years were associated with further deterioration in short
      term but not long-term post-transplant outcomes.

PMID- 29656399
TI  - Differences Between Skilled Nursing Facilities in Risk of Subsequent Long-Term
      Care Placement.
AB  - OBJECTIVES: To determine how the risk of subsequent long-term care (LTC)
      placement varies between skilled nursing facilities (SNFs) and the SNF
      characteristics associated with this risk. DESIGN: Population-based national
      cohort study with participants nested in SNFs and hospitals in a cross-classified
      multilevel model. SETTING: SNFs (N=6,680). PARTICIPANTS: Fee-for-service Medicare
      beneficiaries (N=552,414) discharged from a hospital to a SNF in 2013.
      MEASUREMENTS: Participant characteristics from Medicare data and the Minimum Data
      Set. SNF characteristics from Medicare and Nursing Home Compare. Outcome was a
      stay of 90 days or longer in a LTC nursing home within 6 months of SNF admission.
      RESULTS: Within 6 months of SNF admission, 10.4% of participants resided in LTC.
      After adjustments for participant characteristics, the SNF where a participant
      received care explained 7.9% of the variance in risk of LTC, whereas the prior
      hospital explained 1.0%. Individuals in SNFs with excellent quality ratings had
      22% lower odds of transitioning to LTC than those in SNFs with poor ratings (odds
      ratio=0.78, 95% confidence interval=0.74-0.84). Variation between SNFs and
      associations with quality markers were greater in sensitivity analyses limited to
      individuals least likely to require LTC. Results were essentially the same in a
      number of other sensitivity analyses designed to reduce potential confounding.
      CONCLUSION: Risk of subsequent LTC placement, an important and negatively viewed
      outcome for older adults, varies substantially between SNFs. Individuals in
      higher-quality SNFs are at lower risk.

PMID- 29656400
TI  - PKD regulates actin polymerization, neutrophil deformability, and
      transendothelial migration in response to fMLP and trauma.
AB  - Neutrophils are important mediators of the innate immune defense and of the host
      response to a physical trauma. Because aberrant infiltration of injured sites by
      neutrophils was shown to cause adverse effects after trauma, we investigated how
      neutrophil infiltration could be modulated at the cellular level. Our data
      indicate that protein kinase D (PKD) is a vital regulator of neutrophil
      transmigration. PKD phosphorylates the Cofilin-phosphatase Slingshot-2L (SSH-2L).
      SSH-2L in turn dynamically regulates Cofilin activity and actin polymerization in
      response to a chemotactic stimulus for neutrophils, for example, fMLP. Here, we
      show that inhibition of PKD by two specific small molecule inhibitors results in
      broad, unrestricted activation of Cofilin and strongly increases the F-actin
      content of neutrophils even under basal conditions. This phenotype correlates
      with a significantly impaired neutrophil deformability as determined by optical
      stretcher analysis. Consequently, inhibition of PKD impaired chemotaxis as shown
      by reduced extravasation of neutrophils. Consequently, we demonstrate that
      transendothelial passage of both, neutrophil-like NB4 cells and primary PMNs
      recovered from a hemorrhagic shock trauma model was significantly reduced. Thus,
      inhibition of PKD may represent a promising modulator of the neutrophil response
      to trauma.

PMID- 29656402
TI  - Coordination Complexes of Titanium(IV) and Indium(III) Phthalocyanines with
      Carbonyl-Containing Dyes: The Formation of Singly Bonded Anionic Squarylium
      Dimers.
AB  - Reduction methods for the preparation of coordination complexes of titanium(IV)
      and indium(III) phthalocyanines (Pc) with organic dyes such as indigo,
      thioindigo, and squarylium dye III (SQ) have been developed, which allow one to
      obtain crystalline {cryptand(K+ )}{(cis-indigo-O,O)2- TiIV (Pc2- )}(Cl- )?C6 H4
      Cl2 (1), {cryptand(K+ )}{(cis-thioindigo-O,O)2- InIII (Pc2- )}- ?C6 H4 Cl2 (2),
      and {cryptand(K+ )}{[(SQ)2 -O,O]2- InIII (Pc2- )}- ?3.5 C6 H4 Cl2 (3) complexes.
      The formation of these complexes is accompanied by the reduction of the starting
      dyes to the anionic state. Transition of trans-indigo or trans-thioindigo to the
      cis conformation in 1 and 2 provides coordination of both carbonyl oxygen atoms
      of the dye to TiIV Pc or InIII Pc. SQ is reduced to the radical anion state and
      forms unusual diamagnetic singly bonded (SQ- )2 dimers in 3. These dimers have
      two closely positioned carbonyl oxygen atoms coordinated to InIII Pc. Dianionic
      Pc2- macrocycles have been found in 1-3. The complexes contain two chromophore
      molecules at one metal center. However, their optical spectra are defined mainly
      by absorption bands of the metal phthalocyanines.

PMID- 29656401
TI  - Daily Patterns of Marijuana and Alcohol Co-Use Among Individuals with Alcohol and
      Cannabis Use Disorders.
AB  - BACKGROUND: The study aims were to examine daily associations between marijuana
      and alcohol use and the extent to which the association differs as a function of
      cannabis use disorder (CUD) and/or alcohol use disorder (AUD) diagnosis. METHODS:
      Timeline Followback interview data was collected in a study of veterans (N = 127)
      recruited from a Veterans Affairs hospital who reported at least 1 day of co-use
      of marijuana and alcohol in the past 180 days (22,860 observations). Participants
      reported 40% marijuana use days, 28% drinking days, with 37% meeting DSM-5
      criteria for CUD, 40% for AUD, and 15% for both. Use of marijuana on a given day
      was used to predict a 3-level gender-adjusted drinking variable (heavy: >=5
      (men)/4 (women) drinks; moderate: 1 to 4/3 drinks; or none: 0 drinks). A
      categorical 4-level variable (no diagnosis, AUD, CUD, or both) was tested as a
      moderator of the marijuana-alcohol relationship. RESULTS: Multilevel modeling
      analyses demonstrated that participants were more likely to drink heavily
      compared to moderately (OR = 2.34) and moderately compared to not drinking (OR =
      1.61) on marijuana use days relative to nonuse days. On marijuana use days, those
      with AUD and those with AUD + CUD were more likely to drink heavily (OR = 1.91;
      OR = 2.51, respectively), but those with CUD were less likely to drink heavily
      (OR = 0.32) compared to moderately, nonsignificant differences between any versus
      moderate drinking in interaction models. CONCLUSIONS: Heavy drinking occurs on
      days when marijuana is also used. This association is particularly evident in
      individuals diagnosed with both AUD and CUD and AUDs alone but not in those with
      only CUDs. Findings suggest that alcohol interventions may need to specifically
      address marijuana use as a risk factor for heavy drinking and AUD.

PMID- 29656403
TI  - Saturated Heterocyclic Aminosulfonyl Fluorides: New Scaffolds for Protecting
      Group-Free Synthesis of Sulfonamides.
AB  - Cyclic saturated aminosulfonyl fluorides were synthesized as their HCl salts. The
      compounds were found to be stable upon storage and could be used for the
      protecting-group-free synthesis of sulfonamides. In the presence of the -SO2 F
      group, the nitrogen atom could be modified by means of acylation, arylation, or
      reductive amination to give products that have high potential for the synthesis
      of bioactive compounds.

PMID- 29656404
TI  - Pyoderma gangrenosum in an infant: A case report and review of the literature.
AB  - Pyoderma gangrenosum is a neutrophilic dermatosis that is rare in infancy, with
      only 20 cases reported in the literature. We present a case of infantile pyoderma
      gangrenosum refractory to topical steroids, tacrolimus, and dapsone as well as
      systemic steroids and infliximab that is currently well controlled with the
      addition of oral tacrolimus. To our knowledge, this is the first report of the
      effective, safe use of oral tacrolimus in combination with infliximab for
      infantile pyoderma gangrenosum. We review all current cases of infantile pyoderma
      gangrenosum, as well as tacrolimus and its role in the treatment of this
      condition.

PMID- 29656405
TI  - The Cellie Coping Kit for Children with Injury: Initial feasibility,
      acceptability, and outcomes.
AB  - PURPOSE: Physical and psychological challenges can arise from paediatric injury,
      which can impact child health outcomes. Evidence-based resources to promote
      recovery are limited. The low cost, portable Cellie Coping Kit for Children with
      Injury provides evidence-based strategies to help children manage injury-related
      challenges. This study aimed to describe intervention feasibility and explore
      initial outcomes (learning, quality of life [QOL], and trauma symptoms). METHODS:
      Three independent pilot studies were conducted. Child-parent dyads (n = 61)
      participated in the intervention; ~36% completed a 4-week follow-up assessment.
      RESULTS: Results suggested that the intervention was feasible (e.g., 95% of
      parents would recommend the intervention; >85% reported that it was easy to use).
      Over 70% of participants reported learning new skills. No statistically
      significant differences were detected for children's QOL or trauma symptoms
      preintervention to postintervention. CONCLUSION: Preliminary research suggests
      that the Cellie Coping Kit for Children with Injuries is a feasible, low-cost,
      preventive intervention, which may provide families with strategies to promote
      recovery from paediatric injury. Future research, including a randomized
      controlled trial, ought to further examine targeted long-term intervention
      outcomes.

PMID- 29656406
TI  - A new method for microwave assisted ethanolic extraction of Mentha rotundifolia
      bioactive terpenoids.
AB  - A new microwave-assisted extraction (MAE) method using ethanol as solvent has
      been optimized by means of a Box-Behnken experimental design for the enhanced
      extraction of bioactive terpenoids from Mentha rotundifolia leaves; 100 degrees
      C, 5 min, 1.125 g dry sample: 10 mL solvent and a single extraction cycle were
      selected as optimal conditions. Improved performance of MAE method in terms of
      extraction yield and/or reproducibility over conventional solid-liquid extraction
      and ultrasound assisted extraction was also previously assessed. A comprehensive
      characterization of MAE extracts was carried out by GC-MS. A total of 46
      compounds, mostly terpenoids, were identified; piperitenone oxide and
      piperitenone were the major compounds determined. Several neophytadiene isomers
      were also detected for the first time in MAE extracts. Different procedures
      (solid-phase extraction and activated charcoal (AC) treatment) were also
      evaluated for clean-up of MAE extracts, with AC providing the highest enrichment
      in bioactive terpenoids. Finally, the MAE method here developed is shown as a
      green, fast, efficient and reproducible liquid extraction methodology to obtain
      M. rotundifolia bioactive extracts for further application, among others, as food
      preservatives.

PMID- 29656407
TI  - Recyclable Crosslinked High-Performance Polymers via Adjusting Intermolecular
      Cation-pi Interactions and the Visual Detection of Tensile Strength and Glass
      Transition Temperature.
AB  - Crosslinked high-performance polymers have many industrial applications but are
      difficult to recycle. Visual detection of the physical properties of the
      crosslinked high-performance polymers is useful, but is difficult to achieve. The
      crosslinked high-performance polymers (SPIN) are constructed by using cation-pi
      interactions. The cation-pi interaction between the polymer side chains can be
      easily installed and removed by aqueous treatments at high or low pH,
      respectively, which endow the crosslinked polymer with a recyclable behavior.
      Additionally, the tensile strength and glass transition temperature of the SPIN
      films could be visually detected by taking advantage of the transparency
      decreasing effect of cation to an adjacent indole unit.

PMID- 29656408
TI  - In Silico Tracking of Individual Species Accelerating Progress in Macromolecular
      Engineering and Design.
AB  - The beneficial use of computer simulations to track the microstructural evolution
      of individual species is highlighted in view of macromolecular engineering and
      design, considering two case studies on catalytic polymerization, and both "low"
      (<100) and "high" (>100) chain lengths, that is, i) atom transfer radical
      copolymerization of n-butyl acrylate and styrene aiming at the synthesis of
      functional macrospecies of "identical' chain length; and ii) chain shuttling
      polymerization of ethylene and 1-octene toward the production of segmented block
      copolymers with "soft" and "hard" segments. Model parameters are validated and/or
      tuned based on literature data. The modeling strategy supports the future
      identification of chemical structure-polymer property relationships and is based
      on the combination of principles from polymer reaction engineering, chemistry,
      and physics.

PMID- 29656409
TI  - Investigating Impacts of Climate Change on Irrigation Water Demands and Its
      Resulting Consequences on Groundwater Using CMIP5 Models.
AB  - In this study, the impacts of climate change on crop water requirements and
      irrigation water requirements on the regional cropping pattern were evaluated
      using two climate change scenarios and combinations of 20 GCM models. Different
      models including CROPWAT, MODFLOW, and statistical models were used to evaluate
      the climate change impacts. The results showed that in the future period (2017 to
      2046) the temperature in all months of the year will increase at all stations.
      The average annual precipitation decline in Isfahan, Tiran, Flavarjan, and Lenj
      stations for RCP 4.5 and RCP 8.5 scenarios are 18.6 and 27.6%, 15.2 and 18%, 22.5
      and 31.5%, and 10.5 and 12.1%, respectively. The average increase in the
      evapotranspiration for RCP 4.5 and RCP 8.5 scenarios are about 2.5 and 4.1%,
      respectively. The irrigation water demands increases considerably and for some
      crops, on average 18%. Among the existing crops in the cropping pattern, barley,
      cumin, onion, wheat, and forage crops are more sensitive and their water demand
      will increase significantly. Results indicate that climate change could have a
      significant impact on water resources consumption. By considering irrigation
      efficiency in the region, climate change impacts will result in about 35 to 50
      million m3 /year, over-extraction from the aquifer. This additional exploitation
      causes an extra drop of 0.4 to 0.8 m in groundwater table per year in the
      aquifer. Therefore, with regard to the critical condition of the aquifer,
      management and preventive measures to deal with climate change in the future is
      absolutely necessary.

PMID- 29656410
TI  - Combination of artemisinin-based natural compounds from Artemisia annua L. for
      the treatment of malaria: Pharmacodynamic and pharmacokinetic studies.
AB  - Currently, the most effective antimalarial is artemisinin, which is extracted
      from the leaves of medicinal herb Artemisia annua L. (A. annua). Previous studies
      showed that the complex chemical matrix of A. annua could enhance both the
      bioavailability and efficacy of artemisinin. The present study aims to evaluate
      the efficacy and pharmacokinetic properties of a combination therapy based on
      artemisinin and 3 components from A. annua with high content (arteannuin B,
      arteannuic acid, and scopoletin). In vivo antimalarial activity was assessed
      following a 4-day treatment in murine malaria models (Plasmodium yoelii and
      Plasmodium berghei). Results showed that a much sharper reduction in parasitemia
      (~93%) was found in combination therapy compared with pure artemisinin (~31%),
      indicating pharmacodynamic synergism occurring between artemisinin and arteannuin
      B, arteannuic acid, and scopoletin. Multiple-dose pharmacokinetics further
      demonstrated that combination therapy results in increased area under the curve
      (AUC0->infinity ), Cmax , and t1/2 by 3.78-, 3.47-, and 1.13-fold in healthy
      mice, respectively, and by 2.62-, 1.82-, and 1.22-fold in P. yoelii-infected
      mice, respectively. The calculated oral clearance of combination therapy in
      healthy and P. yoelii-infected mice was also reduced. These findings imply that
      specific components in A. annua might offer a possibility to develop new
      artemisinin-based natural combination therapy for malaria treatment.

PMID- 29656411
TI  - Study on a 65-mer peptide mimetic enzyme with GPx and SOD dual function.
AB  - Excessive reactive oxygen species (ROS) levels are harmful to the body. The
      peroxidase, GPx, and the superoxide dismutase, SOD, are important antioxidant
      enzymes for preventing ROS-induced damage. Se-CuZn-65P is an enzyme mimetic with
      dual GPx and SOD antioxidant function. However, currently, its production is
      mainly based on the cysteine auxotrophic expression technique, which is
      inefficient, expensive, and time consuming. In this study, we combined protein
      engineering and the chemical mutation method to synthesize Se-CuZn-65P. The DNA
      sequence encoding the 65 amino acid peptide with the desired sequence
      transformations to incorporate the SOD and the GPx catalytic sites was cloned and
      expressed in a soluble protein expression vector. The protein yield increased up
      to 152 mg/L, which is 10 times higher than in previous studies. The SOD and GPx
      activity of Se-CuZn-65P was high (1181 U/mg and 753 U/MUmol, respectively). The
      binding constant of glutathione was 5.6 * 104  L.mol-1 , which shows that Se-CuZn
      65P efficiently catalyzed hydrogen peroxide reduction by glutathione.
      Mitochondrial damage experiments confirmed the double protective role of the Se
      CuZn-65P peptide and demonstrated functional synergy between the SOD and the GPx
      domains, which indicates its potential to be used in the treatment of ROS-related
      diseases. Our research may give a new thought to increase the yield of mimic.

PMID- 29656412
TI  - Liver Doppler Findings in Pediatric Patients After Total Pancreatectomy and Islet
      Autotransplantation.
AB  - OBJECTIVES: This study was intended to establish normal values for velocities in
      the hepatic artery and portal veins in pediatric patients after total
      pancreatectomy and islet autotransplantation (TPIAT). METHODS: A retrospective
      review was performed of liver Doppler studies in pediatric patients after TPIAT
      over 6 years at an academic children's hospital. Doppler velocities in the liver
      vasculature and the hepatic artery resistive index were recorded. RESULTS: Sixty
      five pediatric patients were evaluated. There were no cases of portal vein
      thrombosis or other hepatic vascular complications. The mean hepatic artery peak
      systolic velocity was 157.6 cm/s (SE, 60.9 cm/s), with a mean resistive index of
      0.57 (SE, 0.09). The mean main portal vein velocity was 31.9 cm/s (SE, 12.9
      cm/s). CONCLUSIONS: Portal vein thrombosis is rare in pediatric patients after
      TPIAT. A wide range of hepatic artery and portal vein velocities are encountered
      in children immediately after TPIAT without hepatic vascular complications and
      can be considered normal.

PMID- 29656413
TI  - Influence of thermal treatment on the characteristics of major oyster allergen
      Cra g 1 (tropomyosin).
AB  - BACKGROUND: Shellfish, including oysters, often cause allergic reactions in
      adults. Thermal treatment is one of the most common technologies for dealing with
      seafood, which may affect biological properties. The present study aimed to
      evaluate the impact of heating on the conformation and potential allergenicity of
      oyster-derived tropomyosin (Cra g 1). RESULTS: Sodium dodecylsulphate
      polyacrylamide gel electrophoresis showed that there was an apparent band at 35
      kDa of raw tropomyosin after purification and more significant polymers appeared
      in the heated protein. Interestingly, obvious changes in the intensity of the
      circular dichroism signal and 1-anilino-8-naphthalene sulfonate-binding
      fluorescence were observed especially in the case of the roasted form, which was
      associated with an increase in antibody reactivity. The degree of immunoglobulin
      (Ig)E binding of this treatment was demonstrated in the order roasted > boiled >
      raw. Furthermore, sequence alignment and amino acid composition revealed that Cra
      g 1 shared relatively high homology to tropomyosins from other shellfish and was
      also abundant in lysine that was apt to be modified by reducing sugars during
      heating. CONCLUSION: Heated Cra g 1 produces higher IgE reactivity than the raw
      form as a result of the denaturation and formation of polymers. These findings
      will benefit the diagnosis and management of potential allergenicity as a result
      of shellfish. (c) 2018 Society of Chemical Industry.

PMID- 29656414
TI  - Add-On Memantine Treatment for Bipolar II Disorder Comorbid with Alcohol
      Dependence: A 12-Week Follow-Up Study.
AB  - BACKGROUND: Bipolar disorder (BD), especially BD-II, is frequently comorbid with
      alcohol dependence. Because BD-II and alcohol dependence are neurodegenerative
      disorders, agents with anti-inflammatory and neurotrophic effects might provide
      effective therapy. We investigated whether add-on memantine to regular valproic
      acid treatment ameliorated clinical symptoms, reduced alcohol use, and cytokine
      levels, and increased plasma brain-derived neurotrophic factor (BDNF) in BD-II
      patients with comorbid alcohol dependence. METHODS: In a single-arm 12-week
      clinical trial, BD-II patients with comorbid alcohol dependence (n = 45)
      undergoing regular valproic acid treatments were given add-on memantine (5 mg/d).
      Symptom severity, alcohol use, cytokine (plasma tumor necrosis factor-alpha and C
      reactive protein [CRP], transforming growth factor-beta1 [TGF-beta1], interleukin
      8 [IL-8], IL-10), and plasma BDNF levels were regularly assessed. RESULTS: Mean
      within-group decreases in Hamilton Depression Rating Scale (HDRS) and Young Mania
      Rating Scale (YMRS) scores, alcohol use, CRP, BDNF, and IL-8 levels were
      significantly different from baseline after 12 weeks of treatment. We found no
      significant correlation between alcohol use levels and changes in HDRS or YMRS
      scores. The correlation between reduced alcohol use and reduced TGF-beta1 level
      was significant (B = 0.003, p = 0.019). CONCLUSIONS: BD-II comorbid with alcohol
      dependence might benefit from add-on memantine treatment, which significantly
      reduced clinical severity, alcohol use, and plasma cytokine levels, and increased
      BDNF levels.

PMID- 29656415
TI  - Focusing on cancer patients' intentions to use psychooncological support: A
      longitudinal, mixed-methods study.
AB  - OBJECTIVE: Distress screening programs aim to ensure appropriate
      psychooncological support for cancer patients, but many eligible patients do not
      use these services. To improve distress management, we need to better understand
      patients' supportive care needs. In this paper, we report the first key finding
      from a longitudinal study that focused on patients' intentions to use
      psychooncological support and its association with distress and uptake of the
      psychooncology service. METHODS: We conducted a prospective, observational study
      in an Oncology Outpatient Clinic and assessed distress, intention to use
      psychooncological support, and uptake of the psychooncology service by using the
      Distress Thermometer, a semistructured interview, and hospital records. We
      analyzed data with a mixed-methods approach. RESULTS: Of 333 patients (mean age
      61 years; 55% male; 54% Distress Thermometer >= 5), 25% intended to use the
      psychooncology service (yes), 33% were ambivalent (maybe), and 42% reported no
      intention (no). Overall, 23% had attended the psychooncology service 4 months
      later. Ambivalent patients reported higher distress than patients with no
      intention (odds ratio = 1.18, 95% confidence interval [1.06-1.32]) but showed
      significantly lower uptake behavior than patients with an intention (odds ratio =
      14.04, 95% confidence interval [6.74-29.24]). Qualitative analyses revealed that
      ambivalent patients (maybe) emphasized fears and uncertainties, while patients
      with clear intentions (yes/no) emphasized knowledge, attitudes, and coping
      concepts. CONCLUSIONS: We identified a vulnerable group of ambivalent patients
      with high distress levels and low uptake behavior. To optimize distress screening
      programs, we suggest addressing and discussing patients' supportive care needs in
      routine clinical practice.

PMID- 29656416
TI  - Women infected with HIV and the impact of associated sexually transmitted
      infections.
AB  - OBJECTIVE: To review the relationship between concomitant sexually transmitted
      infections in women infected with HIV. METHODS: PubMed and Scopus were searched
      for articles published in English and Portuguese between January 1, 1994, and
      December 31, 2015, using relevant keywords, including AIDS, HIV, female genital
      diseases, and sexually transmitted infections. Articles that associated sexually
      transmitted infections with HIV-infected women were selected for inclusion. Those
      that only investigated prevalence in pregnant women or focused on social or
      behavioral aspects were excluded. RESULTS: Of 108 identified articles, 24 were
      included. When correlated with HIV, genital herpes demonstrated an increased
      recurrence rate and increased replication rate for HIV in the mucosa. In HIV
      positive women, syphilis can cause more genital ulcers. Bacterial vaginosis
      provides a pool of microorganisms that can increase the viral copy levels of
      genital HIV. Chlamydia, gonorrhea, and candidiasis may be more severe and
      complicated in women infected with HIV. CONCLUSIONS: Screening of HIV-positive
      patients who could have other sexually transmitted infections is important to
      protect women and decrease the risk of transmission.

PMID- 29656417
TI  - miRNA regulation of innate immunity.
AB  - MicroRNAs (miRNAs) are small noncoding RNA and are pivotal posttranscriptional
      regulators of both innate and adaptive immunity. They act by regulating the
      expression of multiple immune genes, thus, are the important elements to the
      complex immune regulatory network. Deregulated expression of specific miRNAs can
      lead to potential autoimmunity, immune tolerance, hyper-inflammatory phenotype,
      and cancer initiation and progression. In this review, we discuss the
      contributory pathways and mechanisms by which several miRNAs influence the
      development of innate immunity and fine-tune immune response. Moreover, we
      discuss the consequence of deregulated miRNAs and their pathogenic implications.

PMID- 29656418
TI  - Have we reached the point of primary prevention for atrial fibrillation?

PMID- 29656419
TI  - Oral health knowledge, attitudes, and practices (KAP) in rural Haiti: a 40-year
      follow-up study.
AB  - This paper reports the changed findings over a 40-year period on oral health
      knowledge, attitudes, and practices (KAP) of a very remote and rural population
      living the Jeremie region of Haiti. The far-sighted investigators of that
      original 1970 survey stated in their published 1972 paper that our "...findings
      are descriptive, but have to be accepted tentatively rather than definitively
      because time was short, transportation was difficult, and the small sample that
      had to be used could not random." They further insightfully stated their hopes
      that their "...results may be regarded as an anthropological cultural baseline
      from which to review further findings concerning Haitian dental beliefs." The two
      follow-up surveys in 1997 and 2010 using the same exact KAP questionnaire on the
      same population of rural Haitians living in the Jeremie region fulfilled the
      extraordinary vision of those two initial investigators, Dr. Wesley Young (a
      nationally renowned U.S. public health dental academician) and Paul Rundberg
      (then a dental student at the University of Kentucky).

PMID- 29656420
TI  - Spatially Confined Assembly of Monodisperse Ruthenium Nanoclusters in a
      Hierarchically Ordered Carbon Electrode for Efficient Hydrogen Evolution.
AB  - The redox units of polyaniline (PAni) are used cooperatively, and in situ, to
      assemble ruthenium (Ru) nanoclusters in a hierarchically ordered carbon
      electrode. The oxidized quinonoid imine (QI) units in PAni bond Ru complex ions
      selectively, whereas reduced benzenoid amine (BA) units cannot. By
      electrochemically tuning the ratio of QI to BA, Ru complexes are spatially
      confined in the outer layer of hierarchical PAni frameworks. Carbonization of Ru
      PAni hybrids induces nucleation on the outer surface of the carbon support,
      generating nearly monodisperse Ru nanoclusters. The optimized catalyst has a low
      loading of approximately 2 wt % Ru, but exhibits a mass activity for the hydrogen
      evolution reaction that is about 6.8 times better than commercial 20 wt % Pt/C
      catalyst.

PMID- 29656421
TI  - Effect of cleaning methods on retentive values of saliva-contaminated implant
      supported zirconia copings.
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of different cleaning
      regimens on retentive strength of saliva-contaminated implant-supported zirconia
      copings. MATERIAL AND METHODS: Seventy solid titanium abutments with 5.5 mm
      height (Straumann) were attached to the regular neck implant analogs (Straumann).
      The abutment-analog complex was mounted vertically in an autopolymerized T-shaped
      acrylic resin block. Seventy zirconia copings with an occlusal loop were made.
      The copings were contaminated with fresh human saliva for 1 min (except the
      control group). Afterward, the specimens were washed with water spray for 15 s
      and dried for 15 s. The copings were divided into seven groups according to
      cleaning methods (n = 10). Group 1: no contamination (control group); Group 2:
      water spray rinsing; Group 3: airborne particle abrasion; Group 4: immersion in
      96% isopropanol; Group 5: applying Ivoclean (Ivoclar Vivadent); Group 6: applying
      1% sodium hypochlorite; and Group 7: applying Monobond Plus (Ivoclar Vivadent).
      The copings were luted with a resin luting agent (RelyX Unicem; 3M ESPE). After
      5,000 thermal cycles, the retentive values of the restorations were tested using
      universal testing machine. The dislodging forces were analyzed using one-way
      analysis of variance and the Tukey's HSD tests (alpha = 0.05). RESULTS: The
      copings, which were cleaned with Ivoclean and 96% isopropanol, showed the highest
      retentive values (204.79 +/- 44.49 and 232.65 +/- 71.36, respectively). There was
      a significant difference between the studied groups (F = 2.735; p = .02). Tukey's
      HSD showed that there was no significant difference between the different
      cleaning procedures and control group except water rinsing group (p = .14). The
      lowest retentive value was related to the saliva-contaminated group, which were
      only cleaned with water rinsing method. CONCLUSION: The retentive values of
      zirconia-based restorations were adversely affected by saliva contaminations.
      These restorations can be cleaned by Ivoclean, 96% isopropanol, airborne particle
      abrasion, 1% sodium hypochlorite, or applying Monobond Plus before luting
      procedures.

PMID- 29656422
TI  - Role of lactoferrin and lactoferrin-derived peptides in oral and maxillofacial
      diseases.
AB  - The oral cavity harbors different taxonomic groups, the evolutionary coexistence
      of which develops the oral ecosystem. These resident microorganisms can alter the
      balance between the physiologic and pathologic conditions that affect the host,
      both locally and systemically. This highly sophisticated nature of the oral
      cavity poses a significant therapeutic challenge. Numerous human and animal
      studies have been conducted to potentiate the efficacy and competence of current
      treatments of pathologic conditions as well as to develop novel therapeutic
      modalities. One of these studies is the use of the potent antimicrobial agent
      lactoferrin (LF), which was originally derived from the host immune system. LF is
      an 80-kDa glycoprotein that has a free iron sequestration mechanism with evident
      antimicrobial, anti-tumor, and immunomodulatory properties. A wide range of
      active peptides have been isolated from the N-terminal region of LF, which
      possess antimicrobial activities. In this review, we discuss the role of LF and
      LF-derived peptides under a heterogeneous group of oral and maxillofacial
      conditions, including bacterial, fungal, viral infections; head and neck cancers;
      xerostomia; and implantology-bone-related manifestations.

PMID- 29656423
TI  - Interdisciplinary knowledge exchange across scales in a globally changing marine
      environment.
AB  - The effects of anthropogenic global environmental change on biotic and abiotic
      processes have been reported in aquatic systems across the world. Complex
      synergies between concurrent environmental stressors and the resilience of the
      system to regime shifts, which vary in space and time, determine the capacity for
      marine systems to maintain structure and function with global environmental
      change. Consequently, an interdisciplinary approach that facilitates the
      development of new methods for the exchange of knowledge between scientists
      across multiple scales is required to effectively understand, quantify and
      predict climate impacts on marine ecosystem services. We use a literature review
      to assess the limitations and assumptions of current pathways to exchange
      interdisciplinary knowledge and the transferability of research findings across
      spatial and temporal scales and levels of biological organization to advance
      scientific understanding of global environmental change in marine systems. We
      found that species-specific regional scale climate change research is most
      commonly published, and "supporting" is the ecosystem service most commonly
      referred to in publications. In addition, our paper outlines a trajectory for the
      future development of integrated climate change science for sustaining marine
      ecosystem services such as investment in interdisciplinary education and
      connectivity between disciplines.

PMID- 29656424
TI  - Re: Cardiorespiratory fitness, exercise haemodynamics and birth outcomes: the
      Coronary Artery Risk Development in Young Adults (CARDIA) Study:
      Cardiorespiratory exercise testing years preceding pregnancy and birth outcomes:
      comments on heart rate recovery.

PMID- 29656425
TI  - Atypical aluminium patch tests in children with persistent itching postvaccinal
      nodules.
AB  - Persistent itching nodules related to aluminium-adsorbed vaccines are well known
      in children with frequent positive patch tests to aluminium when tested. We
      report two cases of children with persistent postvaccination nodules who
      presented with atypical eruptions after aluminium patch tests.

PMID- 29656426
TI  - Protein oxidation and proteolysis during roasting and in vitro digestion of fish
      (Acipenser gueldenstaedtii).
AB  - BACKGROUND: Roasted fish enjoys great popularity in Asia, but how roasting and
      subsequent digestion influence the oxidation and proteolysis of fish meat is
      unknown. This study aimed to investigate the effect of roasting time on lipid and
      protein oxidation and their evolution and consequence on proteolysis during
      simulated digestion of fish fillets. RESULTS: Several oxidation markers
      (thiobarbituric acid-reactive substances (TBARS), free thiols, total carbonyls
      and Schiff bases) were employed to assess the oxidation of fish. Sodium dodecyl
      sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and the 2,4,6
      trinitrobenzenesulfonic acid (TNBS) assay for free amino groups were used to
      study the proteolysis during gastrointestinal digestion. The results showed that
      significant lipid and protein oxidative changes occurring in roasted fish fillets
      were reinforced after gastric digestion and were much more intense after
      intestinal digestion. Throughout roasting and digestion, a close interconnection
      between lipid and protein was also manifested as the levels of total carbonyls
      and Schiff bases rose while TBARS fell. Furthermore, free amino groups decreased
      with prolonged roasting time, signifying that protein oxidation before digestion
      resulted in impaired proteolysis during digestion. CONCLUSION: This study
      indicated that the lipid and protein oxidation of fish fillets could be dependent
      on time of roasting, and the oxidation continued to develop and have an impact on
      proteolysis during in vitro digestion. (c) 2018 Society of Chemical Industry.

PMID- 29656427
TI  - Exercise training abrogates age-dependent loss of hypothalamic oxytocinergic
      circuitry and maintains high parasympathetic activity.
AB  - Neuroanatomical studies associating neuronal tract tracing and
      immunohistochemistry identified reciprocal (ascending noradrenergic/descending
      oxytocinergic, OTergic) connections between brainstem cardiovascular nuclei and
      the paraventricular hypothalamic nucleus (PVN). Previous functional studies
      indicated that exercise training (T) augmented the expression/activity of OTergic
      pathway and improve the autonomic control of the heart. Knowing that ageing is
      associated with autonomic dysfunction and sinoaortic denervation blocked T
      induced beneficial effects, we hypothesized that T was able to reduce age
      dependent impairment by improving the afferent signaling to PVN and augmenting
      OTergic modulation of cardiovascular control. We evaluated the combined effects
      of T and age on plastic remodeling of ascending dopamine beta-hydroxylase (DBH+)
      and descending OT+ pathways and correlated them with cardiovascular parameters.
      Male Wistar rats were submitted to T or kept sedentary for 8 weeks. After
      evaluating arterial pressure, heart rate (HR), their variabilities and spectral
      components in conscious rats at rest, brains were harvested to analyze the
      plastic remodeling of brain autonomic nuclei (immunofluorescence + confocal
      microscopy). The density of DBH+ neurons within the nucleus of solitary tract
      (NTS) and caudal ventrolateral medulla, the number of DBH+ terminals overlapping
      OT+ neurons in PVN preautonomic nuclei, as well as the density of OT+ neurons and
      their projections to NTS and dorsal motor nucleus of the vagus were markedly
      reduced in S rats during 8-weeks of inactivity In contrast, these effects were
      completely blocked by T and reversed to a large augmentation of DBH+ and OT+
      densities in both cell bodies and terminals within autonomic nuclei and target
      areas. All plastic changes observed correlated positively with parasympathetic
      activity to the heart (HF-PI, but not with LF-PI) and negatively with resting HR.
      Data indicate that T, by increasing beneficial neuroplastic adaptive changes
      within brainstem-PVN reciprocal network, abrogates age-dependent deleterious
      remodeling and augments parasympathetic modulation of the heart, therefore
      improving autonomic function. This article is protected by copyright. All rights
      reserved.

PMID- 29656428
TI  - Aggregation and conformational changes of silver carp myosin as affected by the
      ultrasound-calcium combination system.
AB  - BACKGROUND: Ultrasound and Ca2+ have been used separately to increase myosin
      properties in fish processing. However, little is know about how myosin changes
      are affected by Ca2+ and ultrasound in combination. The present study aimed to
      investigate the effects of the ultrasound-calcium combination system on
      aggregation and conformational changes of silver carp myosin. RESULTS: Ultrasound
      facilitated a Ca2+ -induced increase in turbidity. As the Ca2+ concentration
      increased from 0 to 100 mmol L-1 , there was an obvious increase in the
      turbidity, solubility and mean hydrated particle size of myosin after ultrasound
      treatment compared to without treatment. Moreover, changes of total and reactive
      SH contents depended on the ultrasound-calcium combination conditions. Under this
      combination system, myosin surface hydrophobicity significantly increased for the
      synergistic effect of ultrasound and Ca2+ . Furthermore, the ultrasound-calcium
      combination conditions could affect myosin gelation, with better gelation
      properties being observed for myosin treated with a combination of 60 mmol L-1
      Ca2+ and 9 min of ultrasound. CONCLUSION: The combination system reported in the
      present study was beneficial for myosin unfolding, facilitating intermolecular
      interactions between Ca2+ and myosin. Ultrasound treatment promoted myosin
      aggregation via the induction of Ca2+ and reduced the critical concentration of
      Ca2+ required to aggregate myosin. In the fish processing industry, this
      combination system can enhance the gelation properties of surimi-based products.
      (c) 2018 Society of Chemical Industry.

PMID- 29656429
TI  - Citalopram attenuated neurobehavioral, biochemical, and metabolic alterations in
      transient middle cerebral artery occlusion model of stroke in male Wistar rats.
AB  - Oxidative stress and inflammation are implicated as cardinal mechanisms of
      neuronal death following stroke. In the present study citalopram (Cit) was
      investigated in a 2 h middle cerebral artery occlusion (MCAo) model of stroke in
      male Wistar rats. Pretreatment, posttreatment (Post Cit) and pre plus
      posttreatment (Pre + Post Cit) with Cit were evaluated for its neuroprotective
      effect. In pretreatment protocol, effect of Cit at three doses (2, 4, and 8
      mg/kg) administered i.p., 1 h prior to MCAo was evaluated using neurological
      deficit score (NDS), motor deficit paradigms, and cerebral infarction 24 h post
      MCAo. In posttreatment and pre plus posttreatment protocol, the effective dose of
      Cit (4 mg/kg) was administered i.p., 0.5 h post-reperfusion (Post Cit) only, and
      1 h prior to MCAo and again at 0.5 h post-reperfusion (Pre + Post Cit),
      respectively. These two groups were assessed for NDS and cerebral infarction.
      Though NDS was significantly reduced in both Post Cit and Pre + Post Cit groups,
      significant reduction in cerebral infarction was evident only in Pre + Post Cit
      group. Infarct volume assessed by magnetic resonance imaging was significantly
      attenuated in Pre + Post Cit group (10.6 +/- 1.1%) compared to MCAo control group
      (18.5 +/- 3.0%). Further, Pre + Post Cit treatment significantly altered 17
      metabolites along with attenuation of malondialdehyde, reduced glutathione,
      matrix metalloproteinases, and apoptotic markers as compared to MCAo control.
      These results support the neuroprotective effect of Cit, mediated through
      amelioration of oxidative stress, inflammation, apoptosis, and altered metabolic
      profile.

PMID- 29656431
TI  - Stishovite's Relative: A Post-Coesite Form of Phosphorus Oxonitride.
AB  - Phosphorus oxonitride (PON) is isoelectronic with SiO2 and may exhibit a similar
      broad spectrum of intriguing properties as silica. However, PON has only been
      sparsely investigated under high-pressure conditions and there has been no
      evidence on a PON polymorph with a coordination number of P greater than 4.
      Herein, we report a post-coesite (pc) PON polymorph exhibiting a stishovite
      related structure with P in a (5+1) coordination. The pc-PON was synthesized
      using the multianvil technique and characterized by powder X-ray diffraction,
      solid-state NMR spectroscopy, TEM measurements and in situ synchrotron X-ray
      diffraction in diamond anvil cells. The structure model was verified by single
      crystal X-ray diffraction at 1.8 GPa and the isothermal bulk modulus of pc-PON
      was determined to K0 =163(2) GPa. Moreover, an orthorhombic PON polymorph (o-PON)
      was observed under high-pressure conditions and corroborated as the stable
      modification at pressures above 17 GPa by DFT calculations.

PMID- 29656430
TI  - Individual differences in stop-related activity are inflated by the adaptive
      algorithm in the stop signal task.
AB  - Research using the Stop Signal Task employing an adaptive algorithm to
      accommodate individual differences often report inferior performance on the task
      in individuals with ADHD, OCD, and substance use disorders compared to non
      clinical controls. Furthermore, individuals with deficits in inhibitory control
      tend to show reduced neural activity in key inhibitory regions during successful
      stopping. However, the adaptive algorithm systematically introduces performance
      related differences in objective task difficulty that may influence the
      estimation of individual differences in stop-related neural activity. This report
      examines the effect that these algorithm-related differences have on the
      measurement of neural activity during the stop signal task. We compared two
      groups of subjects (n = 210) who differed in inhibitory ability using both a
      standard fMRI analysis and an analysis that resampled trials to remove the
      objective task difficulty confound. The results show that objective task
      difficulty influences the magnitude of between-group differences and that
      controlling for difficulty attenuates stop-related activity differences between
      superior and poor inhibitors. Specifically, group differences in the right
      inferior frontal gyrus, right middle occipital gyrus, and left inferior frontal
      gyrus are diminished when differences in objective task difficulty are controlled
      for. Also, when objective task difficulty effects are exaggerated, group
      differences in stop related activity emerge in other regions of the stopping
      network. The implications of these effects for how we interpret individual
      differences in activity levels are discussed.

PMID- 29656432
TI  - Calcium channel blockers and the incidence of breast and prostate cancer: A meta
      analysis.
AB  - WHAT IS KNOWN AND OBJECTIVE: Breast cancer (BCa) and prostate cancer (PCa), both
      hormone-dependent cancers, are the second leading cause of death in both women
      and men, respectively. Calcium channel blockers (CCBs) have been thought to
      increase the risk of cancer by inhibiting calcium signal-mediated apoptosis, but
      the evidence for this association remains inconclusive. We have reviewed
      pertinent literature and pooled data to establish a consensus on the relationship
      of CCB use and the incidence of these two cancers. METHODS: PubMed was used to
      conduct a search for English articles from inception to April 2016. Relevant data
      including study design, number of total participants and CCB users, total cases
      of BCa and PCa, age (mean and/or range), follow-up period and statistical
      outcomes were retrieved. Quality assessment was carried out using Newcastle
      Ottawa system, with the selection of high-quality studies. Summary effects were
      obtained using random- and mixed-effects models, followed by sensitivity
      analysis, and testing for publication bias. RESULTS AND DISCUSSION: This meta
      analysis includes 11 relevant studies for BCa and 6 for PCa. The odds ratio (OR)
      association between BCa and CCB use was 1.14 (95%CI: 1.02, 1.27, P = .02). The OR
      association between PCa and CCB use was 1.12 (95%CI .94-1.35, P = .21). WHAT IS
      NEW AND CONCLUSION: Although a statistically significant association between CCB
      use and incidence of BCa does exist, the limitations of the individual studies
      restrict the clinical application of this relationship. Our meta-regression model
      does newly identify a 9-year latency period of CCB use and a significantly
      increased risk of BCa. No significant association exists between CCB use and the
      incidence of PCa. Our meta-regression shows CCB may have a protective effect upon
      PCa incidence among older populations.

PMID- 29656433
TI  - Antifibrinolytics for heavy menstrual bleeding.
AB  - BACKGROUND: Heavy menstrual bleeding (HMB) is an important physical and social
      problem for women. Oral treatment for HMB includes antifibrinolytic drugs, which
      are designed to reduce bleeding by inhibiting clot-dissolving enzymes in the
      endometrium.Historically, there has been some concern that using the
      antifibrinolytic tranexamic acid (TXA) for HMB may increase the risk of venous
      thromboembolic disease. This is an umbrella term for deep venous thrombosis
      (blood clots in the blood vessels in the legs) and pulmonary emboli (blood clots
      in the blood vessels in the lungs). OBJECTIVES: To determine the effectiveness
      and safety of antifibrinolytic medications as a treatment for heavy menstrual
      bleeding. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility
      (CGF) Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO and two trials
      registers in November 2017, together with reference checking and contact with
      study authors and experts in the field. SELECTION CRITERIA: We included
      randomized controlled trials (RCTs) comparing antifibrinolytic agents versus
      placebo, no treatment or other medical treatment in women of reproductive age
      with HMB. Twelve studies utilised TXA and one utilised a prodrug of TXA (Kabi).
      DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected
      by Cochrane. The primary review outcomes were menstrual blood loss (MBL),
      improvement in HMB, and thromboembolic events. MAIN RESULTS: We included 13 RCTs
      (1312 participants analysed). The evidence was very low to moderate quality: the
      main limitations were risk of bias (associated with lack of blinding, and poor
      reporting of study methods), imprecision and inconsistency.Antifibrinolytics (TXA
      or Kabi) versus no treatment or placeboWhen compared with a placebo,
      antifibrinolytics were associated with reduced mean blood loss (MD -53.20 mL per
      cycle, 95% CI -62.70 to -43.70; I2 = 8%; 4 RCTs, participants = 565; moderate
      quality evidence) and higher rates of improvement (RR 3.34, 95% CI 1.84 to 6.09;
      3 RCTS, participants = 271; moderate-quality evidence). This suggests that if 11%
      of women improve without treatment, 43% to 63% of women taking antifibrinolytics
      will do so. There was no clear evidence of a difference between the groups in
      adverse events (RR 1.05, 95% CI 0.93 to 1.18; 1 RCT, participants = 297; low
      quality evidence). Only one thromboembolic event occurred in the two studies that
      reported this outcome.TXA versus progestogensThere was no clear evidence of a
      difference between the groups in mean blood loss measured using the Pictorial
      Blood Assessment Chart (PBAC) (MD -12.22 points per cycle, 95% CI -30.8 to 6.36;
      I2 = 0%; 3 RCTs, participants = 312; very low quality evidence), but TXA was
      associated with a higher likelihood of improvement (RR 1.54, 95% CI 1.31 to 1.80;
      I2 = 32%; 5 RCTs, participants = 422; low-quality evidence). This suggests that
      if 46% of women improve with progestogens, 61% to 83% of women will do so with
      TXA.Adverse events were less common in the TXA group (RR 0.66, 95% CI 0.46 to
      0.94; I2 = 28%; 4 RCTs, participants = 349; low-quality evidence). No
      thromboembolic events were reported in any group.TXA versus non-steroidal anti
      inflammatory drugs (NSAIDs)TXA was associated with reduced mean blood loss (MD 
      73.00 mL per cycle, 95% CI -123.35 to -22.65; 1 RCT, participants = 49; low
      quality evidence) and higher likelihood of improvement (RR 1.43, 95% CI 1.18 to
      1.74; 12 = 0%; 2 RCTs, participants = 161; low-quality evidence). This suggests
      that if 61% of women improve with NSAIDs, 71% to 100% of women will do so with
      TXA. Adverse events were uncommon and no comparative data were available. No
      thromboembolic events were reported.TXA versus ethamsylateTXA was associated with
      reduced mean blood loss (MD 100 mL per cycle, 95% CI -141.82 to -58.18; 1 RCT,
      participants = 53; low-quality evidence), but there was insufficient evidence to
      determine whether the groups differed in rates of improvement (RR 1.56, 95% CI
      0.95 to 2.55; 1 RCT, participants = 53; very low quality evidence) or withdrawal
      due to adverse events (RR 0.78, 95% CI 0.19 to 3.15; 1 RCT, participants = 53;
      very low quality evidence).TXA versus herbal medicines (Safoof Habis and Punica
      granatum)TXA was associated with a reduced mean PBAC score after three months'
      treatment (MD -23.90 pts per cycle, 95% CI -31.92 to -15.88; I2 = 0%; 2 RCTs,
      participants = 121; low-quality evidence). No data were available for rates of
      improvement. TXA was associated with a reduced mean PBAC score three months after
      the end of the treatment phase (MD -10.40 points per cycle, 95% CI -19.20 to 
      1.60; I2 not applicable; 1 RCT, participants = 84; very low quality evidence).
      There was insufficient evidence to determine whether the groups differed in rates
      of adverse events (RR 2.25, 95% CI 0.74 to 6.80; 1 RCT, participants = 94; very
      low quality evidence). No thromboembolic events were reported.TXA versus
      levonorgestrel intrauterine system (LIUS)TXA was associated with a higher median
      PBAC score than TXA (median difference 125.5 points; 1 RCT, participants = 42;
      very low quality evidence) and a lower likelihood of improvement (RR 0.43, 95% CI
      0.24 to 0.77; 1 RCT, participants = 42; very low quality evidence). This suggests
      that if 85% of women improve with LIUS, 20% to 65% of women will do so with TXA.
      There was insufficient evidence to determine whether the groups differed in rates
      of adverse events (RR 0.83, 95% CI 0.25 to 2.80; 1 RCT, participants = 42; very
      low quality evidence). No thromboembolic events were reported. AUTHORS'
      CONCLUSIONS: Antifibrinolytic treatment (such as TXA) appears effective for
      treating HMB compared to placebo, NSAIDs, oral luteal progestogens, ethamsylate,
      or herbal remedies, but may be less effective than LIUS. There were too few data
      for most comparisons to determine whether antifibrinolytics were associated with
      increased risk of adverse events, and most studies did not specifically include
      thromboembolism as an outcome.

PMID- 29656434
TI  - Evaluation of antioxidant, antiinflammatory, and gastroprotective properties of
      Rubus fruticosus L. fruit juice.
AB  - The juice of R. fruticosus (RFJ) fruits grown in Sicily was analysed for
      polyphenol compounds and tested to evaluate in vitro antioxidant and in vivo
      antiinflammatory and gastroprotective effects. RFJ, containing mainly
      anthocyanins, such as cyanidin derivatives, significant amounts of phenolic
      acids, and smaller amounts of flavonoids, showed significant antioxidant activity
      in DPPH (2,2-diphenyl-1-picrylhydrazyl radical) (4,147.194 +/- 17.199 mg trolox
      equivalent [TE]/100 ml), TE antioxidant capacity (8,312.444 +/- 43.055 mg TE/100
      ml), ferric reducing antioxidant power (2,177.830 +/- 21.015 mg TE/100 ml),
      oxygen radical absorbance capacity (95,377.674 +/- 616.194 MUmol TE/100 ml
      juice), and beta-carotene bleaching (72% +/- 4.58) assay. In vivo studies showed
      that RFJ inhibit significantly the carrageenan-induced paw oedema (63-71%) in
      rats and possess antiinflammatory effects particularly significant in association
      with phenylbutazone (94-96%). In addition, RFJ pretreatment was able to prevent
      the ethanol-induced ulcerogenic effect in rats. All in vivo results were
      corroborated by histopathological observations and are in good agreement with
      antioxidant activity, confirming the relationships between biological effects
      observed and radical scavenging properties of RFJ.

PMID- 29656436
TI  - Comparative analysis of the toxicity of gold nanoparticles in zebrafish.
AB  - The use of nanoparticles - particles that range in size from 1 to 100 nm - has
      become increasingly prevalent in recent years, bringing with it a variety of
      potential toxic effects. Zebrafish embryos were exposed during the 3 day
      postfertilization period to gold nanospheres (GNSs), gold nanorods (GNRs), GNRs
      coated with polystyrene sulphate (PSS-GNRs) and GNRs coated with both PSS and
      polyallamine hydrochloride (PAH-PSS-GNRs). All nanorods were stabilized with
      cetyltrimethylammonium bromide. GNSs were the least toxic of the nanoparticles
      studied, with exposure resulting in no significant changes in mortality, hatching
      or heart rate. Exposure to GNRs and PSS-GNRs resulted in significant increases in
      mortality and significant decreases in hatching and heart rate. Treatment with
      GNRs caused significant changes in the expression of a variety of oxidative
      stress genes. The toxic effects of GNRs were ameliorated by coating them with PSS
      and, to a more marked extent, with a double coating of PSS and polyallamine
      hydrochloride.

PMID- 29656435
TI  - A multi-omic study reveals BTG2 as a reliable prognostic marker for early-stage
      non-small cell lung cancer.
AB  - B-cell translocation gene 2 (BTG2) is a tumour suppressor protein known to be
      downregulated in several types of cancer. In this study, we investigated a
      potential role for BTG2 in early-stage non-small cell lung cancer (NSCLC)
      survival. We analysed BTG2 methylation data from 1230 early-stage NSCLC patients
      from five international cohorts, as well as gene expression data from 3038 lung
      cancer cases from multiple cohorts. Three CpG probes (cg01798157, cg06373167,
      cg23371584) that detected BTG2 hypermethylation in tumour tissues were associated
      with lower overall survival. The prognostic model based on methylation could
      distinguish patient survival in the four cohorts [hazard ratio (HR) range, 1.51
      2.21] and the independent validation set (HR = 1.85). In the expression analysis,
      BTG2 expression was positively correlated with survival in each cohort (HR range,
      0.28-0.68), which we confirmed with meta-analysis (HR = 0.61, 95% CI 0.54-0.68).
      The three CpG probes were all negatively correlated with BTG2 expression.
      Importantly, an integrative model of BTG2 methylation, expression and clinical
      information showed better predictive ability in the training set and validation
      set. In conclusion, the methylation and integrated prognostic signatures based on
      BTG2 are stable and reliable biomarkers for early-stage NSCLC. They may have new
      applications for appropriate clinical adjuvant trials and personalized treatments
      in the future.

PMID- 29656437
TI  - Structural correlates of Openness and Intellect: Implications for the
      contribution of personality to creativity.
AB  - Openness/Intellect (i.e., openness to experience) is the Big Five personality
      factor most consistently associated with individual differences in creativity.
      Recent psychometric evidence has demonstrated that this factor consists of two
      distinct aspects-Intellect and Openness. Whereas Intellect reflects perceived
      intelligence and intellectual engagement, Openness reflects engagement with
      fantasy, perception, and aesthetics. We investigated the extent to which Openness
      and Intellect are associated with variations in brain structure as measured by
      cortical thickness, area, and volume (N = 185). Our results demonstrated that
      Openness was correlated inversely with cortical thickness and volume in left
      middle frontal gyrus (BA 6), middle temporal gyrus (MTG, BA 21), and superior
      temporal gyrus (BA 41), and exclusively with cortical thickness in left inferior
      parietal lobule (BA 40), right inferior frontal gyrus (IFG, BA 45), and MTG (BA
      37). When age and sex were statistically controlled for, the inverse correlations
      between Openness and cortical thickness remained statistically significant for
      all regions except left MTG, whereas the correlations involving cortical volume
      remained statistically significant only for left middle frontal gyrus. There was
      no statistically significant correlation between Openness and cortical area, and
      no statistically significant correlation between Intellect and cortical
      thickness, area, or volume. Our results demonstrate that individual differences
      in Openness are correlated with variation in brain structure-particularly as
      indexed by cortical thickness. Given the involvement of the above regions in
      processes related to memory and cognitive control, we discuss the implications of
      our findings for the possible contribution of personality to creative cognition.

PMID- 29656438
TI  - Renovascular hypertension associated with JAK2 V617F positive myeloproliferative
      neoplasms treated with angioplasty: 2 cases and literature review.
AB  - Myeloproliferative neoplasms (MPNs) with Janus kinase 2 (JAK2) mutation are
      associated with a high risk for occlusive vascular diseases. We report 2 cases of
      renovascular hypertension associated with JAK2 V617F mutation-positive MPNs and
      provide a literature review. In Case 1, a 63-year-old woman had resistant
      hypertension, massive proteinuria, and erythrocytosis. Evaluations revealed right
      renal artery stenosis causing renovascular hypertension and polycythemia vera
      with JAK2 V617F mutation. Renin-angiotensin system inhibitors and subsequent
      angioplasty controlled the blood pressure and the proteinuria resolved. In Case
      2, a 74-year-old woman had resistant hypertension and thrombocytosis. Evaluations
      confirmed left renal artery stenosis and essential thrombocythemia with JAK2
      V617F. Angioplasty cured the hypertension. A literature review of 18 cases
      revealed the following as the most common characteristics of MPN-associated
      renovascular hypertension: manifests primarily in women; is associated with
      untreated polycythemia vera and essential thrombocythemia, concomitant
      leukocytosis, and JAK2 mutation positivity; and is responsive to angioplasty.
      This report demonstrates that JAK2 mutation-positive MPNs are a less common but
      important underlying cause of adult renovascular hypertension.

PMID- 29656439
TI  - Investigating the motives of patients with knee OA undergoing a TKR: A
      qualitative interview study.

PMID- 29656440
TI  - In-plane "superresolution" MRI with phaseless sub-pixel encoding.
AB  - PURPOSE: Acquisition of high-resolution imaging data using multiple excitations
      without the sensitivity to fluctuations of the transverse magnetization phase,
      which is a major problem of multi-shot MRI. THEORY AND METHODS: The concept of
      superresolution MRI based on microscopic tagging is analyzed using an analogy
      with the optical method of structured illumination. Sinusoidal tagging is shown
      to provide subpixel resolution by mixing of neighboring spatial frequency (k
      space) bands. It represents a phaseless modulation added on top of the standard
      Fourier encoding, which allows the phase fluctuations to be discarded at an
      intermediate reconstruction step. Improvements are proposed to correct for tag
      distortions due to magnetic field inhomogeneity and to avoid the propagation of
      Gibbs ringing from intermediate low-resolution images to the final image. The
      method was applied to diffusion-weighted EPI. RESULTS: Artifact-free
      superresolution images can be obtained despite a finite duration of the tagging
      sequence and related pattern distortions by a field map based phase correction of
      band-wise reconstructed images. The ringing effect present in the intermediate
      images can be suppressed by partial overlapping of the mixed k-space bands in
      combination with an adapted filter. High-resolution diffusion-weighted images of
      the human head were obtained with a three-shot EPI sequence despite motion
      related phase fluctuations between the shots. CONCLUSION: Due to its phaseless
      character, tagging-based sub-pixel encoding is an alternative to k-space
      segmenting in the presence of unknown phase fluctuations, in particular those due
      to motion under strong diffusion gradients. Proposed improvements render the
      method practicable in realistic conditions.

PMID- 29656441
TI  - A review on current status of antiviral siRNA.
AB  - Viral diseases like influenza, AIDS, hepatitis, and Ebola cause severe epidemics
      worldwide. Along with their resistant strains, new pathogenic viruses continue to
      be discovered so creating an ongoing need for new antiviral treatments. RNA
      interference is a cellular gene-silencing phenomenon in which sequence-specific
      degradation of target mRNA is achieved by means of complementary short
      interfering RNA (siRNA) molecules. Short interfering RNA technology affords a
      potential tractable strategy to combat viral pathogenesis because siRNAs are
      specific, easy to design, and can be directed against multiple strains of a virus
      by targeting their conserved gene regions. In this review, we briefly summarize
      the current status of siRNA therapy for representative examples from different
      virus families. In addition, other aspects like their design, delivery, medical
      significance, bioinformatics resources, and limitations are also discussed.

PMID- 29656442
TI  - Treatment-emergent hypertension and efficacy in the phase 3 Study of (E7080)
      lenvatinib in differentiated cancer of the thyroid (SELECT).
AB  - BACKGROUND: Hypertension (HTN) is an established class effect of vascular
      endothelial growth factor receptor (VEGFR) inhibition. In the phase 3 Study of
      (E7080) Lenvatinib in Differentiated Cancer of the Thyroid (SELECT) trial, HTN
      was the most frequent adverse event of lenvatinib, an inhibitor of VEGFR1,
      VEGFR2, VEGFR3, fibroblast growth factor receptor 1 (FGFR1), FGFR2, FGFR3, FGFR4,
      platelet-derived growth factor receptor alpha (PDGFRalpha), ret proto-oncogene
      (RET), and stem cell factor receptor (KIT). This exploratory analysis examined
      treatment-emergent hypertension (TE-HTN) and its relation with lenvatinib
      efficacy and safety in SELECT. METHODS: In the multicenter, double-blind SELECT
      trial, 392 patients with progressive radioiodine-refractory differentiated
      thyroid cancer (RR-DTC) were randomized 2:1 to lenvatinib (24 mg/d on a 28-day
      cycle) or placebo. Survival endpoints were assessed with Kaplan-Meier estimates
      and log-rank tests. The influence of TE-HTN on progression-free survival (PFS)
      and overall survival (OS) was analyzed with univariate and multivariate Cox
      proportional hazards models. RESULTS: Overall, 73% of lenvatinib-treated patients
      and 15% of placebo-treated patients experienced TE-HTN. The median PFS for
      lenvatinib-treated patients with (n = 190) and without TE-HTN (n = 71) was 18.8
      and 12.9 months, respectively (hazard ratio [HR], 0.59; 95% confidence interval
      [CI], 0.39-0.88; P = .0085). For lenvatinib-treated patients, the objective
      response rate was 69% with TE-HTN and 56% without TE-HTN (odds ratio, 1.72; 95%
      CI, 0.98-3.01). The median change in tumor size for patients with and without TE
      HTN was -45% and -40%, respectively (P = .2). The median OS was not reached for
      patients with TE-HTN; for those without TE-HTN, it was 21.7 months (HR, 0.43; 95%
      CI, 0.27-0.69; P = .0003). CONCLUSIONS: Although HTN is a clinically significant
      adverse event that warrants monitoring and management, TE-HTN was significantly
      correlated with improved outcomes in patients with RR-DTC, indicating that HTN
      may be predictive for lenvatinib efficacy in this population. Cancer
      2018;124:2365-72. (c) 2018 American Cancer Society.

PMID- 29656443
TI  - Biological evaluation of selected 3,4-dihydro-2(1H)-quinoxalinones and 3,4
      dihydro-1,4-benzoxazin-2-ones: Molecular docking study.
AB  - In order to investigate new potential therapeutically active agents, we
      investigated the biological properties of two small libraries of quinoxalinones
      and 1,4-benzoxazin-2-ones. The results obtained showed that compounds 5, 9-11
      have good cytotoxic activity against HeLa cells where the lowest IC50 value
      (10.46 +/- 0.82 MUM/mL) was measured for compound 10. Additionally, the most
      active compounds (5, 9-11) showed much better selectivity for MRC-5 cells (up to
      17.4) compared to cisplatin. In vitro evaluation of the inhibition of the enzyme
      alpha-glucosidase showed that compounds 10 and 11 exert significant inhibition of
      the enzyme at 52.54 +/- 0.09 and 40.09 +/- 0.49 MUM, respectively. Competitive
      experiments with ethidium bromide (EB) indicated that all tested compounds have
      affinity to displace EB from the EB-DNA complex through intercalation, suggesting
      good competition with EB (Ksv  = (3.1 +/- 0.2), (5.1 +/- 0.1), (5.6 +/- 0.2), and
      (6.3 +/- 0.2) * 103  M-1 ). A molecular docking study was also performed to
      better understand the binding modes and to conclude the structure-activity
      relationships of the synthesized compounds.

PMID- 29656444
TI  - Predicting therapeutic response to fingolimod treatment in multiple sclerosis
      patients.
AB  - AIMS: Fingolimod, an orally active immunomodulatory drug for relapsing-remitting
      multiple sclerosis (RRMS), sequesters T cells in lymph nodes through functional
      antagonism of the sphingosine-1-phosphate receptor, reducing the number of
      potential autoreactive cells that migrate to the central nervous system. However,
      not all RRMS patients respond to this therapy. Our aim was to test the hypothesis
      that by immune-monitoring RRMS patient's leukocyte subpopulations it is possible
      to find biomarkers associated with clinical response to fingolimod. METHODS:
      Prospective study. Analysis of peripheral blood mononuclear cell subpopulations
      by multiparametric flow cytometry, at baseline and +1, +3, +6, +12 months of
      follow-up in 40 RRMS patients starting fingolimod therapy. RESULTS: Fingolimod
      treatment induced a severe lymphopenia affecting mainly T and B cells. A relative
      increase in Treg (memory Treg : 3.8 +/- 1.0% baseline vs 8.8 +/- 4.4% month +1;
      activated Treg : 1.5 +/- 0.7% baseline vs 3.7 +/- 2.1% month +1, P < 0.001) as
      well as transitional B cells (10.5 +/- 12.3% baseline vs 18.7 +/- 14.6% month +1,
      P < 0.001) was observed. Interestingly, lymphocyte subpopulations were already at
      baseline significantly different in responder patients. The percentage of recent
      thymic emigrants (RTE) used to stratify fingolimod responder, and no responder
      patients was the best biomarker (4.0 +/- 1.4% vs 7.4 +/- 1.9%, respectively [P <
      0.001]). CONCLUSION: The results support that immune-monitoring of lymphocyte
      subpopulations in peripheral blood is a promising tool to select RRMS candidate
      for fingolimod treatment.

PMID- 29656445
TI  - The factors influencing retinal thickness in diabetic patients.

PMID- 29656446
TI  - Hemodynamic response function (HRF) variability confounds resting-state fMRI
      functional connectivity.
AB  - PURPOSE: fMRI is the convolution of the hemodynamic response function (HRF) and
      unmeasured neural activity. HRF variability (HRFv) across the brain could, in
      principle, alter functional connectivity (FC) estimates from resting-state fMRI
      (rs-fMRI). Given that HRFv is driven by both neural and non-neural factors, it is
      problematic when it confounds FC. However, this aspect has remained largely
      unexplored even though FC studies have grown exponentially. We hypothesized that
      HRFv confounds FC estimates in the brain's default-mode-network. METHODS: We
      tested this hypothesis using both simulations (where the ground truth is known
      and modulated) as well as rs-fMRI data obtained in a 7T MRI scanner (N = 47,
      healthy). FC was obtained using 2 pipelines: data with hemodynamic deconvolution
      (DC) to estimate the HRF and minimize HRFv, and data with no deconvolution (NDC,
      HRFv-ignored). DC and NDC FC networks were compared, along with regional HRF
      differences, revealing potential false connectivities that resulted from HRFv.
      RESULTS: We found evidence supporting our hypothesis using both simulations and
      experimental data. With simulations, we found that HRFv could cause a change of
      up to 50% in FC. With rs-fMRI, several potential false connectivities
      attributable to HRFv, with majority connections being between different lobes,
      were identified. We found a double exponential relationship between the magnitude
      of HRFv and its impact on FC, with a mean/median error of 30.5/11.5% caused in FC
      by HRF confounds. CONCLUSION: HRFv, if ignored, could cause identification of
      false FC. FC findings from HRFv-ignored data should be interpreted cautiously. We
      suggest deconvolution to minimize HRFv.

PMID- 29656447
TI  - Enhanced Activation of Coordinated Dinitrogen with p-Block Lewis Acids.
AB  - This Concept article highlights recent research on Lewis acid adducts of
      dinitrogen complexes, including our contributions. After a reminder of the early
      works, it is demonstrated that such kind of species offers a new platform for
      dinitrogen functionalization as well as valuable models for the understanding of
      elementary steps of (bio)catalytic cycles. When possible, parallels regarding
      this mode of activation from the orbital point of view are drawn between the
      different systems discussed herein.

PMID- 29656448
TI  - Cephalopod-Derived Biopolymers for Ionic and Protonic Transistors.
AB  - Cephalopods (e.g., squid, octopuses, and cuttlefish) have long fascinated
      scientists and the general public alike due to their complex behavioral
      characteristics and remarkable camouflage abilities. As such, these animals are
      explored as model systems in neuroscience and represent a well-known commercial
      resource. Herein, selected literature examples related to the electrical
      properties of cephalopod-derived biopolymers (eumelanins, chitosans, and
      reflectins) and to the use of these materials in voltage-gated devices (i.e.,
      transistors) are highlighted. Moreover, some potential future directions and
      challenges in this area are described, with the aim of inspiring additional
      research effort on ionic and protonic transistors from cephalopod-derived
      biopolymers.

PMID- 29656449
TI  - Regimen durability in HIV-infected children and adolescents initiating first-line
      antiretroviral therapy in a large public sector HIV cohort in South Africa.
AB  - INTRODUCTION: In April 2010, tenofovir and abacavir replaced stavudine in public
      sector first-line antiretroviral therapy (ART) for children under 20 years old in
      South Africa. The association of both abacavir and tenofovir with fewer side
      effects and toxicities compared to stavudine could translate to increased
      durability of tenofovir or abacavir-based regimens. We evaluated changes over
      time in regimen durability for paediatric patients 3-19 years of age at eight
      public sector clinics in Johannesburg, South Africa. METHODS: Cohort analysis of
      treatment-naive, non-pregnant paediatric patients from 3 to 19 years old
      initiated on ART between April 2004 and December 2013. First-line ART regimens
      before April 2010 consisted of stavudine or zidovudine with lamivudine and either
      efavirenz or nevirapine. Tenofovir and/or abacavir was substituted for stavudine
      after April 2010 in first-line ART. We evaluated the frequency and type of single
      drug substitutions, treatment interruptions and switches to second-line therapy.
      Fine and Gray competing risk regression models were used to evaluate the
      association of antiretroviral drug type with single-drug substitutions, treatment
      interruptions and second-line switches in the first 24 months on treatment.
      RESULTS: Three hundred and ninety-eight (15.3%) single-drug substitutions, 187
      (7.2%) treatment interruptions and 86 (3.3%) switches to second-line therapy
      occurred among 2602 paediatric patients over 24-months on ART. Overall, the rate
      of single-drug substitutions started to increase in 2009, peaked in 2011 at 25%
      and then declined to 10% in 2013, well after the integration of tenofovir into
      paediatric regimens; no patients over the age of 3 were initiated on abacavir for
      first-line therapy. Competing risk regression models showed patients on
      zidovudine or stavudine had upwards of a fivefold increase in single-drug
      substitution vs. patients initiated on tenofovir in the first 24 months on ART.
      Older adolescents also had a two- to threefold increase in treatment
      interruptions and switches to second-line therapy compared to younger patients in
      the first 24 months on ART. CONCLUSIONS: The decline in single-drug substitutions
      is associated with the introduction of tenofovir. Tenofovir use could improve
      regimen durability and treatment outcomes in resource-limited settings.

PMID- 29656450
TI  - Comments on "Perioperative pain management after fibular free flap harvesting for
      head-and-neck reconstruction using mini-catheters to inject local anesthetic: A
      pilot study.

PMID- 29656451
TI  - Patient with mediastinitis caused by delayed mucosal damage after peroral
      endoscopic myotomy.
AB  - Peroral endoscopic myotomy (POEM) is a groundbreaking procedure for treating
      esophageal achalasia, and many reports from various facilities have described its
      safety and efficacy. However, there have been few reports on adverse events.
      Here, we report a case of a patient with mediastinitis caused by delayed mucosal
      damage after POEM. This case was the most severe among all POEM cases at our
      hospital. A 58-year-old man had experienced dysphagia and chest tightness since
      he was around 50 years old. At a previous hospital, he had been diagnosed with
      nonerosive reflux disease and had undergone fundoplication. As his symptoms did
      not improve, he was referred to our department. POEM was able to be finished but
      a stable visual field could not be maintained throughout procedure because of
      strong esophageal contractions. From findings of endoscopy and esophagography
      after POEM, the patient was diagnosed mediastinitis caused by delayed esophageal
      perforation. In this case, conservative treatment (fasting, antibiotic therapy,
      and enteral feeding) was successful. However, the option to administer surgical
      treatment, such as drainage, must not be overlooked.

PMID- 29656452
TI  - The reentry circuit and route in no entry left ventricle situations for
      ventricular tachycardia ablations.

PMID- 29656453
TI  - Chlorogenic Acid Protects Against oxLDL-Induced Oxidative Damage and
      Mitochondrial Dysfunction by Modulating SIRT1 in Endothelial Cells.
AB  - SCOPE: Endothelial dysfunction is an important mechanism in the development of
      atherosclerosis and is thought to be critical for predicting cardiovascular
      diseases. Previous reports suggested that chlorogenic acid (CGA) is a potent
      antioxidant and anti-inflammatory compound. The molecular mechanisms underlying
      the inhibitory effects of CGA on oxLDL-induced oxidative injuries in human
      endothelial cells are still largely unknown. This study is aimed to test the
      hypothesis that CGA protects against oxLDL-facilitated oxidative stress by
      upregulating SIRT1 and to explore the role of AMPK/PGC-1 pathway and
      mitochondrial biogenesis. METHODS AND RESULTS: HUVECs were treated with oxLDL in
      the presence or absence of CGA pretreatment. Our data indicated that CGA
      pretreatment increased SIRT1 deacetylase activity levels. In addition, CGA
      reversed oxLDL-impaired SIRT1 and AMPK/PGC-1 activity and mitigated oxLDL-induced
      oxidative stress and dysfunction of mitochondrial biogenesis. However, silencing
      SIRT1, AMPK, and PGC-1 abated the ability of CGA to protect against oxidative
      stress. Results from the present study also suggested that CGA inhibits oxLDL
      induced endothelial apoptosis through modulating SIRT1 and AMPK/PGC-1 function.
      CONCLUSION: These findings provide new insights into possible molecular
      mechanisms by which CGA mitigates oxLDL-induced endothelial oxidative stress and
      mitochondrial dysfunction by activating SIRT1 and modulating the AMPK/PGC-1
      signaling pathway.

PMID- 29656454
TI  - Is matrix stiffness a cause for malignant transformation of oral submucous
      fibrosis?

PMID- 29656455
TI  - Is radiotherapy the work of the devil?

PMID- 29656456
TI  - An empirical test of the relative and combined effects of land-cover and climate
      change on local colonization and extinction.
AB  - Land-cover and climate change are two main drivers of changes in species ranges.
      Yet, the majority of studies investigating the impacts of global change on
      biodiversity focus on one global change driver and usually use simulations to
      project biodiversity responses to future conditions. We conduct an empirical test
      of the relative and combined effects of land-cover and climate change on species
      occurrence changes. Specifically, we examine whether observed local colonization
      and extinctions of North American birds between 1981-1985 and 2001-2005 are
      correlated with land-cover and climate change and whether bird life history and
      ecological traits explain interspecific variation in observed occurrence changes.
      We fit logistic regression models to test the impact of physical land-cover
      change, changes in net primary productivity, winter precipitation, mean summer
      temperature, and mean winter temperature on the probability of Ontario breeding
      bird local colonization and extinction. Models with climate change, land-cover
      change, and the combination of these two drivers were the top ranked models of
      local colonization for 30%, 27%, and 29% of species, respectively. Conversely,
      models with climate change, land-cover change, and the combination of these two
      drivers were the top ranked models of local extinction for 61%, 7%, and 9% of
      species, respectively. The quantitative impacts of land-cover and climate change
      variables also vary among bird species. We then fit linear regression models to
      test whether the variation in regional colonization and extinction rate could be
      explained by mean body mass, migratory strategy, and habitat preference of birds.
      Overall, species traits were weakly correlated with heterogeneity in species
      occurrence changes. We provide empirical evidence showing that land-cover change,
      climate change, and the combination of multiple global change drivers can
      differentially explain observed species local colonization and extinction.

PMID- 29656457
TI  - Late sampling for automated culture to extend the platelet shelf life to 5 days
      in Germany.
AB  - BACKGROUND: Bacterial contamination of platelet concentrates (PCs) is still a
      major challenge in transfusion medicine. Different methodologic concepts and
      screening strategies have been developed and investigated concerning their
      usability. We evaluated the feasibility of BacT/ALERT automated culture (BacT/A,
      bioMerieux) with late sampling after 3 days at the earliest. STUDY DESIGN AND
      METHODS: Twenty-four bacterial strains isolated from PCs and six relevant strains
      from reference stocks were spiked into apheresis-derived PCs (10-60 colony
      forming units [CFU]/bag). Sampling was performed after 3 days, and bacterial
      detection was investigated using the two detection methods (BacT/A and BactiFlow
      [BF], bioMerieux). The maximum time-to-result of BacT/A was set to less than 12
      hours. RESULTS: All medium- or high-pathogenic strains are capable of
      proliferating to high titers, and 100% of contaminated samples were detected by
      BF and BacT/A (6 to <=12 h incubation); lower detection rates of BacT/A were
      obtained within 6 hours of incubation (<=6 h: 76.2-93.4%). The majority of low
      pathogenic isolates are also capable of growing in PCs (89.7%), showing a
      detection rate of 74.3% for BF versus 54.3% for BacT/A (6 to <=12 h incubation).
      BacT/A failed to detect bacteria within 6 hours of incubation. Certainly, a small
      number of strains did not grow under PC storage conditions and were detectable by
      BacT/A only with increased detection times. CONCLUSIONS: Late sampling after 3
      days at the earliest, combined with reduced BacT/A incubation following the
      negative-to-date concept, offer an alternative opportunity to extend the shelf
      life of PCs from 4 to 5 days in Germany. The sensitivity of BacT/A with late
      sampling is nearly comparable to BF; the time-to-result is considerably longer.

PMID- 29656458
TI  - How ecological communities respond to artificial light at night.
AB  - Many ecosystems worldwide are exposed to artificial light at night (ALAN), from
      streetlights and other sources, and a wide range of organisms has been shown to
      respond to this anthropogenic pressure. This raises concerns about the
      consequences for major ecosystem functions and their stability. However, there is
      limited understanding of how whole ecological communities respond to ALAN, and
      this cannot be gained simply by making predictions from observed single species
      physiological, behavioral, or ecological responses. Research needs to include an
      important building block of ecological communities, namely the interactions
      between species that drive ecological and evolutionary processes in ecosystems.
      Here, we summarize current knowledge about community responses to ALAN and
      illustrate different pathways and their impact on ecosystem functioning and
      stability. We discuss that documentation of the impact of ALAN on species
      interaction networks and trait distributions provides useful tools to link
      changes in community structure to ecosystem functions. Finally, we suggest
      several approaches to advance research that will link the diverse impact of ALAN
      to changes in ecosystems.

PMID- 29656459
TI  - Desktop-Stereolithography 3D-Printing of a Poly(dimethylsiloxane)-Based Material
      with Sylgard-184 Properties.
AB  - The advantageous physiochemical properties of poly(dimethylsiloxane) (PDMS) have
      made it an extremely useful material for prototyping in various technological,
      scientific, and clinical areas. However, PDMS molding is a manual procedure and
      requires tedious assembly steps, especially for 3D designs, thereby limiting its
      access and usability. On the other hand, automated digital manufacturing
      processes such as stereolithography (SL) enable true 3D design and fabrication.
      Here the formulation, characterization, and SL application of a 3D-printable PDMS
      resin (3DP-PDMS) based on commercially available PDMS-methacrylate macromers, a
      high-efficiency photoinitiator and a high-absorbance photosensitizer, is
      reported. Using a desktop SL-printer, optically transparent submillimeter
      structures and microfluidic channels are demonstrated. An optimized blend of PDMS
      methacrylate macromers is also used to SL-print structures with mechanical
      properties similar to conventional thermally cured PDMS (Sylgard-184).
      Furthermore, it is shown that SL-printed 3DP-PDMS substrates can be rendered
      suitable for mammalian cell culture. The 3DP-PDMS resin enables assembly-free,
      automated, digital manufacturing of PDMS, which should facilitate the prototyping
      of devices for microfluidics, organ-on-chip platforms, soft robotics, flexible
      electronics, and sensors, among others.

PMID- 29656460
TI  - Learning from Barres.

PMID- 29656461
TI  - Applicability of internet search index for asthma admission forecast using
      machine learning.
AB  - OBJECTIVE: This study aimed to determine whether a search index could provide
      insight into trends in asthma admission in China. An Internet search index is a
      powerful tool to monitor and predict epidemic outbreaks. However, whether using
      an internet search index can significantly improve asthma admissions forecasts
      remains unknown. The long-term goal is to develop a surveillance system to help
      early detection and interventions for asthma and to avoid asthma health care
      resource shortages in advance. METHODS: In this study, we used a search index
      combined with air pollution data, weather data, and historical admissions data to
      forecast asthma admissions using machine learning. RESULTS: Results demonstrated
      that the best area under the curve in the test set that can be achieved is 0.832,
      using all predictors mentioned earlier. CONCLUSION: A search index is a powerful
      predictor in asthma admissions forecast, and a recent search index can reflect
      current asthma admissions with a lag-effect to a certain extent. The addition of
      a real-time, easily accessible search index improves forecasting capabilities and
      demonstrates the predictive potential of search index.

PMID- 29656462
TI  - KDM1A regulated the osteo/dentinogenic differentiation process of the stem cells
      of the apical papilla via binding with PLOD2.
AB  - OBJECTIVES: Dental tissue-derived mesenchymal stem cells (MSCs)-mediated pulp
      dentin regeneration is considered a potential approach for the regeneration of
      damaged teeth. Enhancing MSC-mediated pulp-dentin regeneration is based on an
      understanding of the molecular mechanisms underlying directed cell
      differentiation process. Histone demethylation enzyme, lysine demethylase 1A
      (KDM1A) can regulate the differentiation of some MSCs, but its role in dental
      tissue-derived MSCs is unclear. MATERIAL AND METHODS: We obtained SCAPs from
      immature teeth. Alkaline phosphatase (ALP) activity assay, Alizarin red staining,
      quantitative calcium analysis, osteogenesis-related genes expression and in vivo
      transplantation experiment were used to explore the osteo/dentinogenic
      differentiation. Co-immunoprecipitation (Co-IP) assay was used to investigate the
      binding protein. RESULTS: Knock-down of KDM1A reduced ALP activity and
      mineralization, promoted the expressions of osteo/dentinogenic differentiation
      markers DSPP, DMP1, BSP and key transcript factors, RUNX2, OSX, DLX2 in SCAPs,
      and also enhanced the osteo/dentinogenesis in vivo. In addition, KDM1A could
      associate with PLOD2 to form protein complex. And knock-down of PLOD2 inhibited
      ALP activity and mineralization, and promoted the expressions of DSPP, DMP1, BSP,
      RUNX2, OSX and DLX2 in SCAPs. CONCLUSIONS: KDM1A might have different role in
      different stages of osteo/dentinogenic differentiation process by binding partner
      with PLOD2, and finally resulted in the inhibited function for the
      osteo/dentinogenesis in SCAPs. Our studies provided a further understanding of
      the regulatory mechanisms of dynamic osteo/dentinogenic differentiation process
      in dental tissue MSCs.

PMID- 29656463
TI  - Rural Health Networks: How Network Analysis Can Inform Patient Care and
      Organizational Collaboration in a Rural Breast Cancer Screening Network.
AB  - PURPOSE: Rural health networks have the potential to improve health care quality
      and access. Despite this, the use of network analysis to study rural health
      networks is limited. The purpose of this study was to use network analysis to
      understand how a network of rural breast cancer care providers deliver services
      and to demonstrate the value of this methodology in this research area. METHODS:
      Leaders at 47 Federally Qualified Health Centers and Rural Health Clinics across
      10 adjacent rural counties were asked where they refer patients for mammograms or
      breast biopsies. These clinics and the 22 referral providers that respondents
      named comprised the network. The network was analyzed graphically and
      statistically with exponential random graph modeling. FINDINGS: Most (96%, n =
      45) of the clinics and referral sites (95%, n = 21) are connected to each other.
      Two clinics of the same type were 62% less likely to refer patients to the same
      providers as 2 clinics of different types (OR = 0.38, 95% CI = 0.29-0.50).
      Clinics in the same county have approximately 8 times higher odds of referring
      patients to the same providers compared to clinics in different counties (OR =
      7.80, CI = 4.57-13.31). CONCLUSIONS: This study found that geographic location of
      resources is an important factor in rural health care providers' referral
      decisions and demonstrated the usefulness of network analysis for understanding
      rural health networks. These results can be used to guide delivery of patient
      care and strengthen the network by building resources that take location into
      account.

PMID- 29656464
TI  - Design and synthesis of novel annulated thienopyrimidines as phosphodiesterase 5
      (PDE5) inhibitors.
AB  - Novel cycloalkene-fused thienopyrimidine analogues with enhanced
      phosphodiesterase 5 (PDE5) inhibitory properties are presented. The structure of
      the reported scaffold was modulated through variation of the terminal cycloalkene
      ring size, as well as by varying the substituents at position 4 through the
      attachment of different groups including aniline, benzylamine,
      cyclohexylethylamine, methyl/acetyl/aryl piperazines, and aryl hydrazones.
      Compound 15Y with a benzylamine substituent and cycloheptene as terminal ring
      showed the highest PDE5 inhibitory activity with an IC50 value as low as 190 nM
      and with good selectivity versus PDE7 and PDE9.

PMID- 29656465
TI  - Structural Characterization of the Interaction of the Fibroblast Growth Factor
      Receptor with a Small Molecule Allosteric Inhibitor.
AB  - The interaction of fibroblast growth factors (FGFs) with their fibroblast growth
      factor receptors (FGFRs) are important in the signaling network of cell growth
      and development. SSR128129E (SSR), a ligand of small molecular weight with
      potential anti-cancer properties, acts allosterically on the extracellular
      domains of FGFRs. Up to now, the structural basis of SSR binding to the D3 domain
      of FGFR remained elusive. This work reports the structural characterization of
      the interaction of SSR with one specific receptor, FGFR3, by NMR spectroscopy.
      This information provides a basis for rational drug design for allosteric FGFR
      inhibitors.

PMID- 29656467
TI  - Single-use disposable digital flexible ureteroscopes: an ex vivo assessment and
      cost analysis.
AB  - OBJECTIVE: To assess and measure the capability of a single-use disposable
      digital flexible ureteroscope, the LithoVueTM (Boston Scientific, Marlborough,
      MA, USA), and to assess if there is a benefit to switching to single-use scopes.
      PATIENTS AND METHODS: The LithoVue was compared to two commonly used reusable
      flexible ureteroscopes (Olympus URF-V [Olympus, Tokyo, Japan] and Karl Storz Flex
      Xc [Karl Storz & Co. KG, Tuttlingen, Germany]) ex vivo. An analysis of reusable
      ureteroscope usage was performed to evaluate damage, durability, and maintenance
      costs. This was then compared to the projected costs of using single-use
      disposable scopes. RESULTS: Flexion, deflection and irrigation flow of the
      LithoVue was equivalent, if not better than the reusable flexible ureteroscopes.
      An analysis of 234 procedures with seven new Olympus URF-V scopes, revealed 15
      scope damages. Staghorn stones and lower pole/mid-zone stones were significant
      risk factors for damage (P = 0.014). Once damage occurred it was likely to occur
      again. Total repair costs were $162 628 (Australian dollars) (L92 411 in Great
      British pounds), the mean cost per case was $695 (L395). Factoring in the
      purchase cost, cleaning and repair costs, the cumulative cost of 28 reusable
      flexible ureteroscopy procedures was ~$50 000 (L28 412). If the LithoVue was
      priced at $1 200 (L682), switching to a single-use scope would cost ~$35 000 (L19
      888). CONCLUSION: The LithoVue is analogous to reusable flexible ureteroscopes in
      regard to standard technical metrics. Depending on its purchase cost it may also
      represent a cost saving for hospitals when compared to the cumulative costs of
      maintaining reusable scopes. Additionally, urologist may consider using the scope
      in cases in which reusable scope damage is anticipated.

PMID- 29656466
TI  - Evaluation of high-fat high-fructose diet treatment in factor VIII (coagulation
      factor)-deficient mouse model.
AB  - Non-alcoholic fatty liver disease (NAFLD)-like conditions enhance the production
      and action of clotting factors in humans. However, studies examining the effect
      of NAFLD due to high-fat high-fructose (HFHF) diet in factor VIII-deficient
      (haemophilia A) animals or patients have not been reported previously. In this
      study, we investigated the individual role of factor VIII in the progression of
      diet-induced NAFLD in the factor 8-/- (F8-/- ) mouse model system and its
      consequences on the haemophilic status of the mice. The F8-/- mice were fed with
      HFHF diet for 14 weeks. Physiological, biochemical, haematological, molecular,
      pathological, and immune histochemical analyses were performed to evaluate the
      effect of this diet. The F8-/- mice developed hepatic steatosis after 14 weeks
      HFHF diet and displayed lower energy metabolism, higher myeloid cell infiltration
      in the liver, decreased platelet count, upregulated de novo fatty acid synthesis,
      lipid accumulation, and collagen deposition. This study helps to understand the
      role of factor VIII in NAFLD pathogenesis and to analyse the severity and
      consequences of steatosis in haemophilic patients as compared to normal
      population. This study suggests that haemophilic animals (F8-/- mice) are highly
      prone to hepatic steatosis and thrombocytopenia.

PMID- 29656468
TI  - Seed dispersal in the mycoheterotrophic orchid Yoania japonica: Further evidence
      for endozoochory by camel crickets.
AB  - Although orthopterans are rarely considered to be effective seed dispersal
      agents, the large flightless crickets known as 'weta' have been suggested to
      function as ecological replacements for small mammals in New Zealand, where such
      mammals are absent. In addition, a recent study reported that camel crickets
      mediate seed dispersal of several heterotrophic plants, including Yoania
      amagiensis in Japan. I investigated the seed dispersal mechanism of Yoania
      japonica because the fruit morphology is similar to Y. amagiensis. Specifically,
      I aimed to determine whether Y. japonica fruits are consumed by camel crickets
      and, if so, whether the seeds defecated by camel crickets remains intact, by
      checking seed viability with TTC staining, and whether germination rate is
      different between seeds collected directly from fruits and defecated seeds by
      comparing in situ seed germinability. The present study provides evidence that
      camel crickets function as seed dispersal agents of Y. japonica. Camel crickets
      were important consumers of Y. japonica fruits, and a substantial portion of the
      consumed seeds remained viable after passing through the digestive tract. In situ
      seed germination experiments revealed that the seeds defecated by camel crickets
      actually germinated in the field. In addition, the germination rate of defecated
      seeds was even higher than that of intact seeds, although the difference was not
      significant. Taken together with recent reports of insect-mediated endozoochory,
      such a seed dispersal system may be common in plants with fleshy indehiscent
      fruits and small seeds, even in locations where other seed dispersal agents are
      present.

PMID- 29656469
TI  - Mortality and nursing home placement of dementia patients in rural and urban
      areas: a cohort study from the Swedish Dementia Registry.
AB  - BACKGROUND: Life in rural and urban areas differs in regard to social support and
      health care. Our aim was to examine the association between nursing home
      placement and survival of patients with dementia living in urban vs. rural areas.
      METHODS: We performed a longitudinal cohort study of patients with dementia at
      time of diagnosis (n = 58 154) and at first follow-up (n = 21 522) including
      patients registered from 2007 through 2014 in the Swedish Dementia Registry
      (SveDem). Descriptive statistics are shown. Odds ratios with 95% CI are presented
      for nursing home placement and hazard ratios for survival analysis. RESULTS: In
      age- and sex-adjusted analyses, patients living in urban areas were more likely
      to be in nursing homes at the time of dementia diagnosis than patients in rural
      areas (1.49, 95% CI: 1.29-1.73). However, there were no differences in rural vs
      urban areas in either survival after dementia diagnosis (urban: 0.99, 0.95-1.04,
      intermediate: 1.00, 0.96-1.04), or nursing home placement at first follow-up
      (urban: 1.00, 0.88-1.13; intermediate: 0.95, 0.85-1.06). CONCLUSION: Persons with
      dementia living in rural areas are less likely to live in a nursing home than
      their urban counterparts at the time of dementia diagnosis, but these differences
      disappear by the time of first follow-up. Differences in access to nursing homes
      between urban and rural settings could explain these findings. Results should be
      considered in the future healthcare decisions to ensure equality of health care
      across rural and urban areas.

PMID- 29656470
TI  - Mechanical and in vitro degradation behavior of magnesium-bioactive glass
      composites prepared by SPS for biomedical applications.
AB  - In order to make magnesium (Mg) a successful candidate for fracture fixation
      devices, it is imperative to control the corrosion rate and enhance its elastic
      modulus. In the present work, we have prepared bioactive glass (BG) reinforced
      magnesium composite using spark plasma sintering (SPS). Simultaneous application
      of heat and pressure during SPS decreased the softening point of BG (600 degrees
      C), allowing it to coat the Mg particles partially. As a result, BG was found
      along the Mg particle boundaries, which was confirmed by elemental mapping.
      Addition of BG improved microhardness and elastic modulus of Mg-BG composites.
      Corrosion behavior was studied by hydrogen evolution and immersion corrosion in
      phosphate buffered saline (PBS). After 64 h of immersion, Mg-10 wt % BG composite
      showed highest corrosion resistance. Quantitative micro-computed tomography
      (micro-CT) results indicated porosity increase in Mg-BG composites during
      immersion. The maximum increase in porosity (1.66%) was noticed for pure Mg while
      the minimum for Mg-10 wt % BG composite. MG63 cell-material interactions, using
      extract method, showed good cytocompatibility for Mg-10 wt % BG composite. The
      concentration of Mg ion in cell culture media was measured using atomic
      absorption spectroscopy after 24 h immersion of Mg/BG composites. The results
      indicated that using BG as reinforcement and SPS as sintering method; we can
      prepare corrosion resistant and high modulus Mg-BG composites that can be used
      for fabricating bone fracture fixation plates. (c) 2018 Wiley Periodicals, Inc. J
      Biomed Mater Res Part B: Appl Biomater, 2018.

PMID- 29656471
TI  - Shape-Controlled Synthesis of Colloidal Metal Nanocrystals by Replicating the
      Surface Atomic Structure on the Seed.
AB  - Controlling the surface structure of metal nanocrystals while maximizing the
      utilization efficiency of the atoms is a subject of great importance. An emerging
      strategy that has captured the attention of many research groups involves the
      conformal deposition of one metal as an ultrathin shell (typically 1-6 atomic
      layers) onto the surface of a seed made of another metal and covered by a set of
      well-defined facets. This approach forces the deposited metal to faithfully
      replicate the surface atomic structure of the seed while at the same time serving
      to minimize the usage of the deposited metal. Here, the recent progress in this
      area is discussed and analyzed by focusing on the synthetic and mechanistic
      requisites necessary for achieving surface atomic replication of precious metals.
      Other related methods are discussed, including the one-pot synthesis,
      electrochemical deposition, and skin-layer formation through thermal annealing.
      To close, some of the synergies that arise when the thickness of the deposited
      shell is decreased controllably down to a few atomic layers are highlighted,
      along with how the control of thickness can be used to uncover the optimal
      physicochemical properties necessary for boosting the performance toward a range
      of catalytic reactions.

PMID- 29656472
TI  - In vitro and in vivo characterization of an interleukin-15 antagonist peptide by
      metabolic stability, 99m Tc-labeling, and biological activity assays.
AB  - Interleukin (IL)-15 is an inflammatory cytokine that constitutes a validated
      therapeutic target in some immunopathologies, including rheumatoid arthritis
      (RA). Previously, we identified an IL-15 antagonist peptide named [K6T]P8, with
      potential therapeutic application in RA. In the current work, the metabolic
      stability of this peptide in synovial fluids from RA patients was studied.
      Moreover, [K6T]P8 peptide was labeled with 99m Tc to investigate its stability in
      human plasma and its biodistribution pattern in healthy rats. The biological
      activity of [K6T]P8 peptide and its dimer was evaluated in CTLL-2 cells, using 3
      different additives to improve the solubility of these peptides. The half-life of
      [K6T]P8 in human synovial fluid was 5.88 +/- 1.73 minutes, and the major chemical
      modifications included peptide dimerization, cysteinylation, and methionine
      oxidation. Radiolabeling of [K6T]P8 with 99m Tc showed a yield of approximately
      99.8%. The 99m Tc-labeled peptide was stable in a 30-fold molar excess of
      cysteine and in human plasma, displaying a low affinity to plasma proteins.
      Preliminary biodistribution studies in healthy Wistar rats suggested a slow
      elimination of the peptide through the renal and hepatic pathways. Although
      citric acid, sucrose, and Tween 80 enhanced the solubility of [K6T]P8 peptide and
      its dimer, only the sucrose did not interfere with the in vitro proliferation
      assay used to assess their biological activity. The results here presented,
      reinforce nonclinical characterization of the [K6T]P8 peptide, a potential agent
      for the treatment of RA and other diseases associated with IL-15 overexpression.

PMID- 29656473
TI  - Rapid Electron Transfer of Stacked Heterodimers of Perylene Diimide Derivatives
      in a DNA Duplex.
AB  - The preparation of homo- and heterocomplexes composed of the parent perylene
      diimide (PH) and pyrrolidine-substituted perylene diimide (PN) in DNA and rapid
      electron transfer in these complexes, which has been analyzed by steady-state
      fluorescence and femtosecond transient absorption measurements, have been
      demonstrated. The DNA molecules possessing PH and PN were prepared through a
      recently developed method that involved the reaction of enzymatically generated
      abasic sites with the amino groups of the perylene diimide molecules, through
      which these molecules can be incorporated as base surrogates within the DNA base
      stack. Melting temperature analysis showed that the PH and PN monomers, and their
      homo- and heterodimers, contribute to the stabilization of the DNA duplex, and is
      comparable to that of natural base pairs. Fluorescence measurements showed that
      PH in a single-stranded oligopyrimidine showed a strong fluorescence, whereas the
      fluorescence of PH was completely quenched upon pairing with PN (PH/PN) through
      duplex formation. The transient absorption measurements showed that a rapid
      electron-transfer reaction in the stacked PH/PN heterodimer occurred on a sub
      picosecond timescale, which allowed highly efficient fluorescence quenching. The
      PH/PN pair, which served as a fluorophore and quencher, were utilized to design
      molecular beacon probes with a high signal/noise ratio. The PH/PN pair was also
      capable of forming a stable, stacked dimer structure and induced rapid electron
      transfer that could serve as a good signal reporter for fluorescent nucleic acid
      detection.

PMID- 29656474
TI  - Assessment of motivation levels and associated factors among the nursing staff of
      tertiary-level government hospitals.
AB  - The present study assessed the motivation level of nurses working in 3 highly
      decorated tertiary-level government hospitals of India and also underpins the
      factors attributing to motivation levels. A sequential mixed-method design was
      used in this study wherein 400 nurses working in 5 units of nursing care in the
      hospitals were enrolled based upon proportionate random stratified sampling
      techniques. A self-administered questionnaire with Likert scale was developed
      based upon scale used by Mbindyo et al. The attributes of motivation were then
      categorized into external and internal attributes. For the qualitative component,
      participants with varied responses in quantitative data were selected and
      interviewed. Overall mean motivation score of the nursing staff was found 3.57 +/
      0.93, which was higher for extrinsic motivational attributes (3.67 +/- 0.88) as
      compared with intrinsic attributes (3.47 +/- 0.98). The intrinsic motivational
      attribute of organizational commitment was rated highest followed by general
      motivation, conscientiousness, and self-efficacy. Personal issues, timeliness,
      and burnout were prime discouraging attributes among study participants.
      Sociodemographic characteristics and work profile characteristics showed
      significant relationship with the attributes of motivation. This study
      underscores the significance of different attributes of motivation which needs to
      be considered while framing administrative strategies and policy guidelines by
      authorities.

PMID- 29656475
TI  - Hydrogenation of Multiple Bonds by Geminal Aminoborane-Based Frustrated Lewis
      Pairs.
AB  - The hydrogenation reaction of multiple bonds that is mediated by geminal
      aminoborane-based frustrated Lewis pairs (FLPs) has been explored by means of
      density functional theory calculations. It was found that the release of the
      activated dihydrogen occurred in a concerted, yet highly asynchronous, manner.
      The physical factors that control the transformation were quantitatively
      described in detail by using the activation strain model of reactivity in
      combination with the energy decomposition analysis method. This approach
      suggested a cooperative double hydrogen-transfer mechanism, which involves the
      initial migration of the protic (N)H followed by the nucleophilic attack of the
      (B)H hydride to the carbon atom of the multiple bond. The influence of both the
      substituents directly attached to the boron atom of the initial FLP and the
      nature of the multiple bond on the transformation was also investigated.

PMID- 29656476
TI  - Topiramate-induced secondary angle closure: salient points in management.

PMID- 29656477
TI  - Structure-Property Relations in New Cyclic Galactaric Acid Derived Monomers and
      Polymers Therefrom: Possibilities and Challenges.
AB  - In order to fully exploit the potential of carbohydrate-based monomers, different
      (and some new) functionalities are introduced on galactaric acid via
      acetalization, and subsequently, partially-biobased polyamides are prepared
      therefrom via polycondensation in the melt. Compared to nonsubstituted linear
      monomer, faster advancement of the reaction is observed for the different
      biacetal derivatives of galactaric acid. This kinetic observation is of great
      significance since it allows conducting a polymerization reaction at lower
      temperatures than normally expected for polyamides, which allows overcoming
      typical challenges (e.g., thermal degradation) encountered upon polymerization of
      carbohydrate-derived monomers in the melt. The polymers derived from the modified
      galactaric acid monomers vary in terms of glass transition temperature, thermal
      stability, hydrophilicity, and functionality.

PMID- 29656478
TI  - Transplantation of Neural Progenitor Cells Expressing Glial Cell Line-Derived
      Neurotrophic Factor into the Motor Cortex as a Strategy to Treat Amyotrophic
      Lateral Sclerosis.
AB  - Early dysfunction of cortical motor neurons may underlie the initiation of
      amyotrophic lateral sclerosis (ALS). As such, the cortex represents a critical
      area of ALS research and a promising therapeutic target. In the current study,
      human cortical-derived neural progenitor cells engineered to secrete glial cell
      line-derived neurotrophic factor (GDNF) were transplanted into the SOD1G93A ALS
      rat cortex, where they migrated, matured into astrocytes, and released GDNF. This
      protected motor neurons, delayed disease pathology and extended survival of the
      animals. These same cells injected into the cortex of cynomolgus macaques
      survived and showed robust GDNF expression without adverse effects. Together this
      data suggests that introducing cortical astrocytes releasing GDNF represents a
      novel promising approach to treating ALS. Stem Cells 2018;36:1122-1131.

PMID- 29656479
TI  - Fiber length and concentration: Synergistic effect on mechanical and cellular
      response in wet-laid poly(lactic acid) fibrous scaffolds.
AB  - In the area of biomaterials, fibers not only offer increased mechanical response,
      but also serve as an extracellular matrix mimicking morphology to direct cellular
      attachment and proliferation. While biologically similar in morphology, soft, and
      flexible hydrogel materials have low mechanical properties. For applications in
      tissue engineering, the lack of directional cues and attachment regions within
      the biogels is undesired as cells require a guide for adequate attachment and
      organized proliferation. In this work, we have investigated the role of
      poly(lactic acid) (PLA) fiber length and concentration as a reinforcement phase
      in a gelatin hydrogel matrix and the resultant mechanical and cellular responses.
      With increasing fiber length and concentration, the ultimate tensile strength,
      modulus, and toughness increased for the samples. Similarly, for shorter fiber
      lengths, the loss and storage modulus increased with fiber concentration. After
      seeding human mesenchymal stem cells (hMSCs) onto the neat fibrous scaffolds it
      was found that the fabrication process imparted no cytotoxicity. Furthermore, it
      was the concentrations and lengths of fiber both caused discernable differences
      in cell viability at the extreme values. Fibers of all lengths, when in a 4.0 wt
      % concentration, had a decrease in cell viability after 10 days while the 12.7 mm
      fibers showed a similar response at 2.0 wt %, but all stayed about 90% viability.
      With increased incubation time, hMSCs became elongated with increased
      proliferation. These results indicate that the wet-lay process is a rapid and
      scalable method by which fibrous 3D-scaffolds can be produced to reinforce
      hydrogel matrices. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B:
      Appl Biomater, 2018.

PMID- 29656480
TI  - Development of a risk-prediction model for Middle East respiratory syndrome
      coronavirus infection in dialysis patients.
AB  - Introduction The Middle East respiratory syndrome coronavirus (MERS-CoV)
      infection can cause transmission clusters and high mortality in hemodialysis
      facilities. We attempted to develop a risk-prediction model to assess the early
      risk of MERS-CoV infection in dialysis patients. Methods This two-center
      retrospective cohort study included 104 dialysis patients who were suspected of
      MERS-CoV infection and diagnosed with rRT-PCR between September 2012 and June
      2016 at King Fahd General Hospital in Jeddah and King Abdulaziz Medical City in
      Riyadh. We retrieved data on demographic, clinical, and radiological findings,
      and laboratory indices of each patient. Findings A risk-prediction model to
      assess early risk for MERS-CoV in dialysis patients has been developed.
      Independent predictors of MERS-CoV infection were identified, including chest
      pain (OR = 24.194; P = 0.011), leukopenia (OR = 6.080; P = 0.049), and elevated
      aspartate aminotransferase (AST) (OR = 11.179; P = 0.013). The adequacy of this
      prediction model was good (P = 0.728), with a high predictive utility (area under
      curve [AUC] = 76.99%; 95% CI: 67.05% to 86.38%). The prediction of the model had
      optimism-corrected bootstrap resampling AUC of 71.79%. The Youden index yielded a
      value of 0.439 or greater as the best cut-off for high risk of MERS infection.
      Discussion This risk-prediction model in dialysis patients appears to depend
      markedly on chest pain, leukopenia, and elevated AST. The model accurately
      predicts the high risk of MERS-CoV infection in dialysis patients. This could be
      clinically useful in applying timely intervention and control measures to prevent
      clusters of infections in dialysis facilities or other health care settings. The
      predictive utility of the model warrants further validation in external samples
      and prospective studies.

PMID- 29656481
TI  - Toward in vivo quantification of induced RF currents on long thin conductors.
AB  - PURPOSE: Most MR-guided catheter-based procedures, and imaging of patients with
      implanted medical devices, are currently contraindicated due to a significant
      risk of heating associated with induced RF currents. The induced RF current
      produces a corresponding artifact which can be used to remotely characterize
      current and safely predict RF heating. Application of this remote technique in
      vivo to safely quantify RF heating risk may allow for execution of many scans
      currently contraindicated. Sources of phase other than induced RF current may
      present difficulty in practical in vivo. METHODS: A custom ultra-short echo time
      (UTE) sequence was developed to minimize unwanted phase contributions. A phantom
      experiment was performed to compare current characterization using a stock
      gradient-echo (GRE) sequence and the custom UTE sequence following calibration of
      the temperature measurement apparatus using a previously published heating
      prediction technique. Animal experiments were used to investigate the feasibility
      of using the UTE sequence to quantify RF heating. RESULTS: Current
      characterization and heating prediction with a stock GRE sequence was equivalent
      to that with the custom UTE sequence. Heating measurements and image-based
      predictions in animal experiments agreed within error in all experiments.
      CONCLUSION: Through comparison of measured heating and image-based prediction,
      feasibility of using a custom UTE sequence to quantify RF heating risk in vivo
      was demonstrated.

PMID- 29656482
TI  - Kindlin-3 negatively regulates the release of neutrophil extracellular traps.
AB  - Neutrophils fight infections by generating reactive oxygen species (ROS) and
      extracellular traps (NETs). However, how neutrophils modulate ROS/NET generation
      is mechanistically unclear. Kindlin-3, an essential integrin activator expressed
      in hematopoietic cells, is required to support integrin-mediated neutrophil
      recruitment during inflammation. Here, we report a novel role of kindlin-3 in
      regulating ROS/NET generation in neutrophils. When overexpressing kindlin-3 in
      neutrophil-like differentiated HL-60 cells (HL-60N), ROS/NET generation from
      these cells were significantly suppressed. Interestingly, overexpression of a
      kindlin-3 mutant that is defective for interacting with integrins in HL-60N cells
      still inhibited ROS/NET generation, suggesting that the role of kindlin-3 in
      inhibiting ROS/NET signaling may be independent of its binding to integrins.
      Consistently, knockdown of kindlin-3 in HL-60N cells led to enhanced ROS/NET
      generation. In addition, bone marrow neutrophils isolated from kindlin-3
      deficient mice showed elevated ROS/NET generation when compared with WT
      counterparts. As expected, overexpression of exogenous kindlin-3 in mouse
      neutrophils could suppress NET release ex vivo and in vivo. Collectively, these
      results demonstrate that kindlin-3 in neutrophils is involved in modulating the
      ROS/NET signaling, providing a novel mechanism for fine-tuning neutrophil
      behaviors during inflammation.

PMID- 29656483
TI  - Stress distributions in internal resorption cavities restored with different
      materials at different root levels: A finite element analysis study.
AB  - The aim of this study was to evaluate the stresses within simulated roots with
      internal resorption cavities at the apical, middle and coronal root levels, after
      obturation with gutta-percha and/or MTA utilising finite element analysis (FEA).
      Mandibular premolar teeth with internal resorption cavities at different root
      levels were modelled. Models were restored with gutta-percha and/or MTA. An
      oblique force of 300 N was applied and stress evaluations were carried out. In
      the MTA-filled resorption models, the stresses were distributed more
      homogeneously than the gutta-percha filled models, and the stress concentrations
      were lower in the remaining dentinal tissues. If the whole root is considered,
      the fully gutta-percha-filled models generated the highest stress values.
      Differences between the fully MTA-filled models and hybrid techniques were
      present only in the apical resorption models. Both the MTA and combination of MTA
      and gutta-percha can be suggested for use in clinical practice, in cases of
      internal root resorption cavity obturation.

PMID- 29656484
TI  - Did poor eyesight influence Goya's late works? Medicine and art history in search
      for an interpretation of Goya's late paintings.
AB  - PURPOSE: The aim of this article is to 'determine' the scope of Goya's eyesight
      difficulties and assess the extent to which those difficulties might explain his
      style of painting in the last years of his life. METHODS: We analyse the
      correspondence and late works of the Aragonese painter Francisco de Goya y
      Lucientes (1746-1828), who has been admired for his use of colour, his energetic
      loose brushstrokes, his disregard for details and his bold compositions, as well
      as for his different artistic styles throughout his life. RESULTS: The evolution
      of Goya's style of painting in his later works seems to have been the consequence
      of an eyesight condition, probably age-related cataracts at an advanced stage.
      The faded dark backgrounds, which become blurred with the silhouette of the
      person portrayed, could indicate a certain degree of eye strain. This can be
      traced in all these works, but is especially evident in the unfinished portrait
      of Pio de Molina (1827-1828), as well as in the portraits of Mariano Goya, the
      artist's grandson (1827), and Jacques Galos (1826). CONCLUSION: It has been
      considered that the late and isolated Goya's sight problems were a belated
      consequence of his severe illness of 1792. Nevertheless, in our opinion, this is
      a simplistic explanation and, given the painter's age, it is logical to presume
      that their cause could be age-related lens opacities. This article argues that
      medicine may become a subsidiary science to art history, as it can provide
      empirical evidence of the way painters' illnesses may have a strong impact on
      their artworks.

PMID- 29656485
TI  - A case of secretory carcinoma of the parotid gland provides cytological clues for
      the differential diagnosis of this disease.

PMID- 29656486
TI  - The Effect of End Group and Molecular Weight on the Yellowness of Polyetherimide.
AB  - The effects of end group and molecular weight on the yellowness of telechelic
      polyetherimide (PEI) are investigated. Electron-withdrawing dianhydride end
      groups reduce the yellowness and increase the transparency of PEI regardless of
      the molecular weight. Electron-donating phenyl, amine, and phthalic end groups
      increase the yellowness of PEI but the effect depends on the molecular weight. As
      the molecular weight is increased, the yellowness of PEIs with electron-donating
      end groups initially decreases due to a decreasing end-group density and then
      increases due to an increasing probability of charge-transfer complex formation.
      The systematic study reveals the correlations among yellowness, end group, and
      molecular weight of PEIs. The correlations can be used for designing highly
      transparent PEIs and other high-performance polymers.

PMID- 29656487
TI  - Experimental Research Requires Valid and Sensitive Measures of Alcohol Intake,
      and This is a Step in the Right Direction: Commentary on Leeman and Colleagues
      (2018).

PMID- 29656488
TI  - Importance of coverage and quality for impact of nutrition interventions
      delivered through an existing health programme in Bangladesh.
AB  - Understanding implementation of interventions is critical to illuminate if, how,
      and why the interventions achieve impact. Alive & Thrive integrated a nutrition
      intervention into an existing maternal, neonatal, and child health (MNCH)
      programme in Bangladesh, documenting improvements in women's micronutrient
      supplement intake and dietary diversity. Here, we examined how well the nutrition
      intervention was implemented and which elements of implementation explained
      intervention impact. Survey data were collected in 2015 and 2016 from frontline
      health workers (FLW) and households in areas randomized to nutrition-focused MNCH
      (intensified interpersonal counselling, community mobilization, distribution of
      free micronutrient supplements, and weight-gain monitoring) or standard MNCH
      (antenatal care with standard nutrition counselling). Seven intervention elements
      were measured: time commitment, training quality, knowledge, coverage,
      counselling quality, supervision, and incentives. Multiple regression was used to
      derive difference-in-differences (DID) estimates. Using village-level endline
      data, path analysis was used to determine which elements most explained
      intervention impacts. FLWs in both areas were highly committed and well
      supervised. Coverage was high (>90%) for counselling, supplement provision, and
      weight-gain monitoring. Improvements were significantly greater for nutrition
      focused MNCH, versus standard MNCH, for training quality (DID: 2.42 points of
      10), knowledge (DID: 1.20 points), delivery coverage (DID: 4.16 points), and
      counselling quality (DID: 1.60 points). Impact was substantially explained by
      coverage and delivery quality. In conclusion, integration nutrition intervention
      into the MNCH programme was feasible and well-implemented. Although differences
      in coverage and counselling quality most explained impacts, all intervention
      elements-particularly FLW training and performance-were likely important to
      achieving impact.

PMID- 29656489
TI  - Photocatalytic Hybrid Semiconductor-Metal Nanoparticles; from Synergistic
      Properties to Emerging Applications.
AB  - Hybrid semiconductor-metal nanoparticles (HNPs) manifest unique combined and
      often synergetic properties stemming from the materials combination. These
      structures exhibit spatial charge separation across the semiconductor-metal
      junction upon light absorption, enabling their use as photocatalysts. So far, the
      main impetus of photocatalysis research in HNPs addresses their functionality in
      solar fuel generation. Recently, it was discovered that HNPs are functional in
      efficient photocatalytic generation of reactive oxygen species (ROS). This has
      opened the path for their implementation in diverse biomedical and industrial
      applications where high spatially temporally resolved ROS formation is essential.
      Here, the latest studies on the synergistic characteristics of HNPs are
      summarized, including their optical, electrical, and chemical properties and
      their photocatalytic function in the field of solar fuel generation is briefly
      discussed. Recent studies are then focused concerning photocatalytic ROS
      formation with HNPs under aerobic conditions. The emergent applications of this
      capacity are then highlighted, including light-induced modulation of enzymatic
      activity, photodynamic therapy, antifouling, wound healing, and as novel
      photoinitiators for 3D-printing. The superb photophysical and photocatalytic
      properties of HNPs offer already clear advantages for their utility in scenarios
      requiring on-demand light-induced radical formation and the full potential of
      HNPs in this context is yet to be revealed.

PMID- 29656490
TI  - Cross-cultural adaptation, reliability and validity of the Spanish version of the
      Neonatal Skin Risk Assessment Scale.
AB  - AIM: To adapt the Neonatal Skin Risk Assessment Scale to the Spanish context and
      to test its validity and reliability. BACKGROUND: Currently, in Spain there are
      no validated scales to evaluate the risk of pressure ulcers in infants. METHOD:
      The research was performed in 10 neonatal units. Overall, we use an observational
      study design, but divided it in to three stages. In the first stage, the
      transcultural adaptation of the scale and its content validation was performed.
      For the second stage, the inter-rater/intra-rater agreement and construct
      validity were evaluated using a cross-sectional design. Finally, in the third
      stage, a cohort study to analyse pressure ulcers' incidence, diagnostic tests and
      the cut-off points of the scale was performed. RESULTS: In the first phase, the
      content validity index was 0.93. In the second phase (336 neonates), the intra
      rater reliability was 0.93 and the inter-rater reliability was 0.97. The
      construct validity has shown a two-dimensional model that fits better,
      representing "pressure duration and intensity" and "skin immaturity." In the
      third phase (268 neonates) the best values were those presented by the score 17:
      receiver operating characteristic curve was 0.84, showing a sensitivity of
      91.18%, specificity of 76.50%, positive predictive value of 36.05% and negative
      predictive value of 98.35%. CONCLUSION: The scale has shown evidence of validity
      and reliability to measure the neonatal risk of pressure ulcers in the Spanish
      context. IMPLICATIONS FOR NURSING MANAGEMENT: Pressure ulcers are an adverse
      event recognised in paediatric units and specifically in neonatal units. The
      intent of the Spanish Neonatal Skin Risk Assessment Scale is to identify
      hospitalised neonates requiring prevention measures and their specific risk
      factors, to provide useful diagnostic information to improve the neonatal skin
      care into Spanish speaking countries. The Neonatal Skin Risk Assessment Scale
      could ensure the efficient and effective allocation of limited preventive
      resources, support clinical and management decisions, allow risk-adjusted cases
      in epidemiological studies, facilitate the development of risk assessment
      protocols and serve as evidence in litigation cases. All these features could
      facilitate developing best practice in nursing management and improve the quality
      and safety of neonatal care.

PMID- 29656491
TI  - Recurrent F8 and F9 gene variants result from a founder effect in two large
      French haemophilia cohorts.
AB  - INTRODUCTION: Haemophilia A (HA) and haemophilia B (HB) are X-linked recessive
      diseases, caused by a large number of pathogenic variants in the F8 and F9 genes.
      With the exception of introns 22 and 1 inversions which are frequent in severe HA
      cases, about 2000 unique variants in F8 and 1000 in F9 have been described in
      databases and their recurrence remains limited. AIM AND METHODS: During routine
      analysis, we identified two recurrent missense variants, the F8 gene c.1244C>T,
      p.Ala415Val variant in 27 HA patients and the F9 gene c.835G>A, p.Ala279Thr
      variant in 34 HB patients, in two groups of haemophiliac patients from two
      different regions of France. We aimed to identify whether these variants result
      from a founder effect. We performed haplotype reconstruction after analysis of
      extragenic and intragenic polymorphic markers. The ESTIAGE programme was used to
      estimate the age of the variant. RESULTS: We identified a common ancestral
      haplotype HA1, in all the HA patients sharing the p.Ala415Val variant, and HB1
      for 22 of 34 HB patients sharing the p.Ala279Thr variant. The estimated time of
      occurrence of the founder variant was between the 13th and 17th century (95% CI:
      16 to 29 generations) for the F8 variant and between the 3rd and the 11th century
      for the F9 variant (95% CI: 44 to 72 generations). CONCLUSION: This study
      supports a founder effect for these two variants in the two largest reported
      cohorts of haemophilia patients with an identical variant. These pathogenic
      variants are among the three most early reported variants in haemophilia.

PMID- 29656492
TI  - PD-1 Blockade Cellular Vesicles for Cancer Immunotherapy.
AB  - Cancer cells resist to the host immune antitumor response via multiple
      suppressive mechanisms, including the overexpression of PD-L1 that exhausts
      antigen-specific CD8+ T cells through PD-1 receptors. Checkpoint blockade
      antibodies against PD-1 or PD-L1 have shown unprecedented clinical responses.
      However, limited host response rate underlines the need to develop alternative
      engineering approaches. Here, engineered cellular nanovesicles (NVs) presenting
      PD-1 receptors on their membranes, which enhance antitumor responses by
      disrupting the PD-1/PD-L1 immune inhibitory axis, are reported. PD-1 NVs exhibit
      a long circulation and can bind to the PD-L1 on melanoma cancer cells.
      Furthermore, 1-methyl-tryptophan, an inhibitor of indoleamine 2,3-dioxygenase can
      be loaded into the PD-1 NVs to synergistically disrupt another immune tolerance
      pathway in the tumor microenvironment. Additionally, PD-1 NVs remarkably increase
      the density of CD8+ tumor infiltrating lymphocytes in the tumor margin, which
      directly drive tumor regression.

PMID- 29656493
TI  - Oxygen consumption trajectory flattening-yet another cardiopulmonary exercise
      testing parameter in chronic heart failure.

PMID- 29656495
TI  - Randomized controlled clinical study assessing two membranes for guided bone
      regeneration of peri-implant bone defects: 3-year results.
AB  - OBJECTIVES: To assess two- and three-dimensional changes of the peri-implant
      tissues as well as clinical, biological, and radiological outcomes of implants
      having been treated with resorbable or nonresorbable membranes at 3 years.
      MATERIALS AND METHODS: Twenty-three patients were re-examined after having
      received a single-tooth implant in the esthetic zone in conjunction with guided
      bone regeneration (GBR) using either a resorbable (RES) or a titanium-reinforced
      nonresorbable membrane (N-RES) and demineralized bovine bone mineral. Volumetric
      and linear as well as clinical and radiographic measurements were performed at
      crown insertion (baseline), at 1 year (FU-1) and 3 years (FU-3). Statistics were
      performed by means of parametric and nonparametric tests. RESULTS: Minor, but
      ongoing buccal volume loss was observed in both groups during the 3-year follow
      up. A slightly higher volume loss was observed in group RES (-0.22 mm) compared
      to N-RES (-0.14 mm) at 1 year (FU-1), but aligned at 3 years (FU-3) RES (-0.30
      mm) N-RES (-0.32 mm). All changes over time were statistically significantly
      different within (p < .05), but not between the groups (p > .05). Stable median
      interproximal bone levels after 3 years (FU-3); 0.26 mm (0.04; 0.36) (RES) and
      0.14 mm (0.08; 0.20) (N-RES) and healthy tissues (BOP, PD) were obtained with
      both membranes. CONCLUSIONS: Both treatment modalities resulted in minor, but
      ongoing contour changes of the peri-implant tissues. Stable interproximal bone
      levels and healthy tissues can be obtained with membranes up to 3 years.

PMID- 29656494
TI  - Oxidized LDL phagocytosis during foam cell formation in atherosclerotic plaques
      relies on a PLD2-CD36 functional interdependence.
AB  - The uptake of cholesterol carried by low-density lipoprotein (LDL) is tightly
      controlled in the body. Macrophages are not well suited to counteract the
      cellular consequences of excess cholesterol leading to their transformation into
      "foam cells," an early step in vascular plaque formation. We have uncovered and
      characterized a novel mechanism involving phospholipase D (PLD) in foam cell
      formation. Utilizing bone marrow-derived macrophages from genetically PLD
      deficient mice, we demonstrate that PLD2 (but not PLD1)-null macrophages cannot
      fully phagocytose aggregated oxidized LDL (Agg-Ox-LDL), which was phenocopied
      with a PLD2-selective inhibitor. We also report a role for PLD2 in coupling Agg
      oxLDL phagocytosis with WASP, Grb2, and Actin. Further, the clearance of LDL
      particles is mediated by both CD36 and PLD2, via mutual dependence on each other.
      In the absence of PLD2, CD36 does not engage in Agg-Ox-LDL removal and when CD36
      is blocked, PLD2 cannot form protein-protein heterocomplexes with WASP or Actin.
      These results translated into humans using a GEO database of microarray
      expression data from atheroma plaques versus normal adjacent carotid tissue and
      observed higher values for NFkB, PLD2 (but not PLD1), WASP, and Grb2 in the
      atheroma plaques. Human atherectomy specimens confirmed high presence of PLD2
      (mRNA and protein) as well as phospho-WASP in diseased arteries. Thus, PLD2
      interacts in macrophages with Actin, Grb2, and WASP during phagocytosis of Agg-Ox
      LDL in the presence of CD36 during their transformation into "foam cells." Thus,
      this study provides new molecular targets to counteract vascular plaque formation
      and atherogenesis.

PMID- 29656496
TI  - Fast and sensitive HPLC/UV method for cefazolin quantification in plasma and
      subcutaneous tissue microdialysate of humans and rodents applied to
      pharmacokinetic studies in obese individuals.
AB  - Antimicrobial prophylactic dosing of morbidly obese patients may differ from
      normal weighted individuals owing to alterations in drug tissue distribution.
      Drug subcutaneous tissue distribution can be investigated by microdialysis
      patients and animals. The need for cefazolin prophylactic dose adjustment in
      obese patients remains under discussion. The paper describes the validation of an
      HPLC-UV method for cefazolin quantification in plasma and microdialysate samples
      from clinical and pre-clinical studies. A C18 column with an isocratic mobile
      phase was used for drug separation, with detection at 272 nm. Total and unbound
      cefazolin lower limit of quantitation was 5 MUg/mL in human plasma, 2 MUg/mL in
      rat plasma, and 0.5 and 0.025 MUg/mL in human and rat microdialysate samples,
      respectively. The maximum intra- and inter-day imprecisions were 10.7 and 8.1%,
      respectively. The inaccuracy was <9.7%. The limit of quantitation imprecision and
      inaccuracy were < 15%. Cefazolin stability in the experimental conditions was
      confirmed. Cefazolin plasma concentrations and subcutaneous tissue penetration
      were determined by microdialysis in morbidly obese patients (2 g i.v. bolus) and
      diet-induced obese rats (30 mg/kg i.v. bolus) using the method. This method has
      the main advantages of easy plasma clean-up and practicability and has proven to
      be useful in cefazolin clinical and pre-clinical pharmacokinetic investigations.

PMID- 29656497
TI  - Altered brain function in persistent postural perceptual dizziness: A study on
      resting state functional connectivity.
AB  - This study used resting state functional magnetic resonance imaging (rsfMRI) to
      investigate whole brain networks in patients with persistent postural perceptual
      dizziness (PPPD). We compared rsfMRI data from 38 patients with PPPD and 38
      healthy controls using whole brain and region of interest analyses. We examined
      correlations among connectivity and clinical variables and tested the ability of
      a machine learning algorithm to classify subjects using rsfMRI results. Patients
      with PPPD showed: (a) increased connectivity of subcallosal cortex with left
      superior lateral occipital cortex and left middle frontal gyrus, (b) decreased
      connectivity of left hippocampus with bilateral central opercular cortices, left
      posterior opercular cortex, right insular cortex and cerebellum, and (c)
      decreased connectivity between right nucleus accumbens and anterior left temporal
      fusiform cortex. After controlling for anxiety and depression as covariates,
      patients with PPPD still showed decreased connectivity between left hippocampus
      and right inferior frontal gyrus, bilateral temporal lobes, bilateral insular
      cortices, bilateral central opercular cortex, left parietal opercular cortex,
      bilateral occipital lobes and cerebellum (bilateral lobules VI and V, and left I
      IV). Dizziness handicap, anxiety, and depression correlated with connectivity in
      clinically meaningful brain regions. The machine learning algorithm correctly
      classified patients and controls with a sensitivity of 78.4%, specificity of
      76.9%, and area under the curve = 0.88 using 11 connectivity parameters. Patients
      with PPPD showed reduced connectivity among the areas involved in multisensory
      vestibular processing and spatial cognition, but increased connectivity in
      networks linking visual and emotional processing. Connectivity patterns may
      become an imaging biomarker of PPPD.

PMID- 29656498
TI  - Helicobacter pylori infection-induced H3Ser10 phosphorylation in stepwise gastric
      carcinogenesis and its clinical implications.
AB  - BACKGROUND: Our previous works have demonstrated that Helicobacter pylori (Hp)
      infection can alter histone H3 serine 10 phosphorylation status in gastric
      epithelial cells. However, whether Helicobacter pylori-induced histone H3 serine
      10 phosphorylation participates in gastric carcinogenesis is unknown. We
      investigate the expression of histone H3 serine 10 phosphorylation in various
      stages of gastric disease and explore its clinical implication. MATERIALS AND
      METHODS: Stomach biopsy samples from 129 patients were collected and stained with
      histone H3 serine 10 phosphorylation, Ki67, and Helicobacter pylori by
      immunohistochemistry staining, expressed as labeling index. They were categorized
      into nonatrophic gastritis, chronic atrophic gastritis, intestinal metaplasia,
      low-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia, and
      intestinal-type gastric cancer groups. Helicobacter pylori infection was
      determined by either 13 C-urea breath test or immunohistochemistry staining.
      RESULTS: In Helicobacter pylori-negative patients, labeling index of histone H3
      serine 10 phosphorylation was gradually increased in nonatrophic gastritis,
      chronic atrophic gastritis, intestinal metaplasia groups, peaked at low-grade
      intraepithelial neoplasia, and declined in high-grade intraepithelial neoplasia
      and gastric cancer groups. In Helicobacter pylori-infected patients, labeling
      index of histone H3 serine 10 phosphorylation followed the similar pattern as
      above, with increased expression over the corresponding Helicobacter pylori
      negative controls except in nonatrophic gastritis patient whose labeling index
      was decreased when compared with Helicobacter pylori-negative control. Labeling
      index of Ki67 in Helicobacter pylori-negative groups was higher in gastric cancer
      than chronic atrophic gastritis and low-grade intraepithelial neoplasia groups,
      and higher in intestinal metaplasia group compared with chronic atrophic
      gastritis group. In Helicobacter pylori-positive groups, Ki67 labeling index was
      increased stepwise from nonatrophic gastritis to gastric cancer except slightly
      decrease in chronic atrophic gastritis group. In addition, we noted that histone
      H3 serine 10 phosphorylation staining is accompanied with its location changes
      from gastric gland bottom expanded to whole gland as disease stage progress.
      CONCLUSIONS: These results indicate that stepwise gastric carcinogenesis is
      associated with altered histone H3 serine 10 phosphorylation, Helicobacter pylori
      infection enhances histone H3 serine 10 phosphorylation expression in these
      processes; it is also accompanied with histone H3 serine 10 phosphorylation
      location change from gland bottom staining expand to whole gland expression. The
      results suggest that epigenetic dysregulation may play important roles in
      Helicobacter pylori-induced gastric cancer.

PMID- 29656499
TI  - Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      analysis of 36 blood group alleles among 396 Thai samples reveals region-specific
      variants.
AB  - BACKGROUND: Blood group phenotype variation has been attributed to potential
      resistance to pathogen invasion. Variation was mapped in blood donors from
      Lampang (northern region) and Saraburi (central region), Thailand, where malaria
      is endemic. The previously unknown blood group allele profiles were characterized
      and the data were correlated with phenotypes. The high incidence of the Vel
      negative phenotype previously reported in Thais was investigated. STUDY DESIGN
      AND METHODS: DNA from 396 blood donors was analyzed by matrix-assisted laser
      desorption/ionization-time-of-flight mass spectrometry. Outliers were
      investigated by serology and DNA sequencing. Allele discrimination assays for
      SMIM1 rs1175550A/G and ACKR1 rs118062001C/T were performed and correlated with
      antigen expression. RESULTS: All samples were phenotyped for Rh, MNS, and K.
      Genotyping/phenotyping for RhD, K, and S/s showed 100% concordance. Investigation
      of three RHCE outliers revealed an e-variant antigen encoded by RHCE*02.22.
      Screening for rs147357308 (RHCE c.667T) revealed a frequency of 3.3%. MN typing
      discrepancies in 41 samples revealed glycophorin variants, of which 40 of 41 were
      due to Mia . Nine samples (2.3%) were heterozygous for FY*01W.01 (c.265C > T),
      and six samples (1.5%) were heterozygous for JK*02N.01. All samples were wildtype
      SMIM1 homozygotes with 97% homozygosity for rs1175550A. CONCLUSIONS: Matrix
      assisted laser desorption/ionization-time-of-flight mass spectrometry is an
      efficient method for rapid routine genotyping and investigation of outliers
      identified novel variation among our samples. The expected high prevalence of the
      Mi(a+) phenotype was observed from both regions. Of potential clinical relevance
      in a region where transfusion-dependent thalassemia is common, we identified two
      RHCE*02 alleles known to encode an e-variant antigen.

PMID- 29656500
TI  - Mitochondria, glycogen, and lipid droplets in skeletal muscle during testosterone
      treatment and strength training: a randomized, double-blinded, placebo-controlled
      trial.
AB  - Low testosterone levels in aging men are associated with insulin resistance.
      Mitochondrial dysfunction, changes in glycogen metabolism, and lipid accumulation
      are linked to insulin resistance in skeletal muscle. In this randomized, double
      blinded, placebo-controlled study, we investigated the effects of six-month
      testosterone replacement therapy (TRT) and strength training (ST) on
      mitochondrial, glycogen, and lipid droplet (LD) content in skeletal muscle of
      aging men with subnormal bioavailable testosterone (BioT) levels. Mitochondrial,
      glycogen, and LD volume fractions in muscle biopsies were estimated by
      transmission electron microscopy. Insulin sensitivity (insulin-stimulated Rd) and
      body composition were assessed by euglycemic-hyperinsulinemic clamp and dual X
      ray absorptiometry, respectively. TRT significantly increased total testosterone
      levels, BioT, and lean body mass (LBM) (p < 0.05), whereas percent body fat
      decreased (p < 0.05), and insulin sensitivity was unchanged. Baseline
      mitochondrial volume fraction correlated inversely with percent body fat (rho = 
      0.43; p = 0.003). Delta-mitochondrial fraction correlated positively with Delta
      total testosterone (rho = 0.70; p = 0.02), and Delta-glycogen fraction correlated
      inversely with Delta-LBM (rho = -0.83; p = 0.002) during six-month TRT, but no
      significant changes were observed in mitochondrial, glycogen, and LD volume
      fractions during TRT and ST. In conclusion, in this exploratory small-scale
      study, the beneficial effects of six-month TRT on total testosterone, LBM, and
      percent body fat were not followed by significant changes in fractions of
      mitochondria, glycogen, or lipid in skeletal muscle of aging men with lowered
      testosterone levels. Six-month ST or combined three-month ST+TRT did not change
      intramyocellular mitochondria, glycogen, and LD fractions compared to placebo.
      However, further studies with a larger sample size are needed.

PMID- 29656501
TI  - Radiotherapy complications - another sub-specialty area of urology?

PMID- 29656502
TI  - Integrating Desalination and Energy Storage using a Saltwater-based Hybrid Sodium
      ion Supercapacitor.
AB  - Ever-increasing freshwater scarcity and energy crisis problems require efficient
      seawater desalination and energy storage technologies; however, each target is
      generally considered separately. Herein, a hybrid sodium-ion supercapacitor,
      involving a carbon-coated nano-NaTi2 (PO4 )3 -based battery anode and an
      activated-carbon-based capacitive cathode, is developed to combine desalination
      and energy storage in one device. On charge, the supercapacitor removes salt in a
      flowing saltwater electrolyte through Cl- electrochemical adsorption at the
      cathode and Na+ intercalation at the anode. Discharge delivers useful electric
      energy and regenerates the electrodes. This supercapacitor can be used not only
      for energy storage with promising electrochemical performance (i.e., high power,
      high efficiency, and long cycle life), but also as a desalination device with
      desalination capacity of 146.8 mg g-1 , much higher than most reported capacitive
      and battery desalination devices. Finally, we demonstrate renewables to usable
      electric energy and desalted water through combining commercial photovoltaics and
      this hybrid supercapacitor.

PMID- 29656503
TI  - Generation of Aryl and Heteroaryl Magnesium Reagents in Toluene by Br/Mg or Cl/Mg
      Exchange.
AB  - The alkylmagnesium alkoxide sBuMgOR?LiOR (R=2-ethylhexyl), which was prepared as
      a 1.5 m solution in toluene, undergoes very fast Br/Mg exchange with aryl and
      heteroaryl bromides, producing aryl and heteroaryl magnesium alkoxides
      (ArMgOR?LiOR) in toluene. These Grignard reagents react with a broad range of
      electrophiles, including aldehydes, ketones, allyl bromides, acyl chlorides,
      epoxides, and aziridines, in good yields. Remarkably, the related reagent sBu2
      Mg?2 LiOR (R=2-ethylhexyl) undergoes Cl/Mg exchange with various electron-rich
      aryl chlorides in toluene, producing diorganomagnesium species of type Ar2 Mg?2
      LiOR, which react well with aldehydes and allyl bromides.

PMID- 29656504
TI  - Efficacy and safety of MYL-1501D vs insulin glargine in patients with type 1
      diabetes after 52 weeks: Results of the INSTRIDE 1 phase III study.
AB  - AIM: To test the safety and efficacy of MYL-1501D, a proposed insulin glargine
      biosimilar, in patients with type 1 diabetes mellitus (T1DM). METHODS: The safety
      and efficacy of MYL-1501D and reference insulin glargine were evaluated in
      INSTRIDE 1, a 52-week, open-label, randomized, phase III study in patients with
      T1DM. The primary objective was to determine whether once-daily MYL-1501D was non
      inferior to once-daily insulin glargine when administered in combination with
      mealtime insulin lispro based on change in glycated haemoglobin (HbA1c) from
      baseline to week 24. Secondary endpoints were changes in fasting plasma glucose,
      insulin dose, self-monitored blood glucose and immunogenicity from baseline, and
      occurrences of hypoglycaemic, nocturnal hypoglycaemic and adverse events up to
      week 52. RESULTS: Overall, 558 patients were randomized 1:1 to MYL-1501D or
      reference insulin glargine in combination with thrice-daily mealtime insulin
      lispro for 52 weeks. The mean change in HbA1c from baseline to week 24 was 0.14%
      (standard error [SE] 0.054; 95% confidence interval [CI] 0.033, 0.244) for MYL
      1501D and 0.11% (SE 0.054; 95% CI 0.007, 0.220) for reference insulin glargine.
      MYL-1501D had a safety profile similar to that of reference insulin glargine and
      was well tolerated in patients with T1DM up to week 52. CONCLUSIONS: The upper
      95% CI limit for mean change in HbA1c at week 24 indicated that MYL-1501D was non
      inferior to reference insulin glargine. There were no clinically meaningful
      differences between groups in incidence of overall and nocturnal hypoglycaemia,
      local or systemic reactions, safety or immunogenicity.

PMID- 29656505
TI  - Facile N-Alkylation/N'-Arylation Process: A Direct Approach to Aromatic
      Aminoalkyl Amines.
AB  - An intriguing C-N transformation involving a catalyst-free N-alkylation/N'
      arylation process in a multicomponent reaction with secondary amines, cyclic
      tertiary amines and electron-deficient aryl halides has been described. In this
      case, the N-alkylation of secondary amines, utilizing cyclic tertiary amines as
      alkyl group sources, is enabled by a facile C-N cleavage. Such an operationally
      simple method could facilitate access to aromatic aminoalkyl amines, nitrogen
      containing bioactive molecules, in good to excellent yields.

PMID- 29656506
TI  - Enantiospecific Total Syntheses of (+)-Hapalindole H and (-)-12-epi-Hapalindole
      U.
AB  - Enantiospecific total syntheses of (+)-hapalindole H and (-)-12-epi-hapalindole U
      as well as the formal syntheses of (+)-hapalindole Q and (+)-12-epi-fischerindole
      U isothiocyanate have been described. Key steps of our approach feature
      expedient, highly regio- and diastereoselective Lewis acid catalyzed Friedel
      Crafts reaction of indole with cyclic allylic alcohols and intramolecular
      reductive Heck reaction. Efficiency of the synthetic route also relies on an
      alkynyl aluminate complex driven regioselective nucleophilic epoxide opening from
      a sterically hindered site.

PMID- 29656507
TI  - Construction and application of a Xanthomonas campestris CGMCC15155 strain that
      produces white xanthan gum.
AB  - In the industrial production of xanthan gum using Xanthomonas campestris
      CGMCC15155, large amounts of ethanol are required to extract xanthan gum from the
      fermentation broth and remove xanthomonadin impurities. To reduce the amount of
      ethanol and the overall production cost of xanthan gum, a xanthomonadin-deficient
      strain of CGMCC15155 was constructed by inserting the Vitreoscilla globin (vgb)
      gene, under the control of the LacZ promoter, into the region of the pigA gene,
      which is involved in xanthomonadin synthesis. The insertion of vgb inactivated
      pigA, resulting in the production of white xanthan gum. The lack of
      xanthomonadins resulted in a decreased yield of xanthan gum. However, the
      expression product of vgb gene, VHb, could increase the metabolism of X.
      campestris, which allowed the production of xanthan gum to reach wild-type levels
      in the engineered strain. The yield, molecular weight, and rheological properties
      of the xanthan gum synthesized by the engineered and wild-type bacteria were
      essentially the same. When the same volume of ethanol was used, the whiteness
      values of the xanthan gum extracted from engineered and wild-type bacteria were
      65.20 and 38.17, respectively. To extract xanthan gum with the same whiteness,
      three and seven times the fermentation volume of ethanol was required for the
      engineered and wild-type strains, respectively. Thus, the engineered train
      reduced the requirement for ethanol in xanthan gum production by 133.3%. The
      results demonstrated that the engineered bacteria used less ethanol, thus
      reducing the downstream processing cost in xanthan gum production.

PMID- 29656508
TI  - The 3rd World Conference on Kisspeptin, "Kisspeptin 2017: Brain and
      Beyond":Unresolved questions, challenges and future directions for the field.
AB  - The 3rd World Conference on Kisspeptin, "Kisspeptin 2017: Brain and Beyond" was
      held March 30-31 at the Rosen Centre Hotel in Orlando, Florida, providing an
      international forum for multidisciplinary scientists to meet and share cutting
      edge research on kisspeptin biology and its relevance to human health and
      disease. The meeting built upon previous world conferences focused on the role of
      kisspeptin and associated peptides in the control of gonadotropin-releasing
      hormone (GnRH) secretion and reproduction. Based on recent discoveries, the scope
      of this meeting was expanded to include functions of kisspeptin and related
      peptides in other physiological systems including energy homeostasis, pregnancy,
      ovarian and uterine function, and thermoregulation. In addition, discussions
      addressed the translation of basic knowledge of kisspeptin biology to the
      treatment of disease, with the goal of seeking consensus about the best
      approaches to improve human health. The two-day meeting featured a non
      traditional structure, with each day starting with poster sessions followed by
      lunch discussions and facilitated large-group sessions with short presentations
      to maximize the exchange of new, unpublished data. Topics were identified by a
      survey prior to the meeting, and focused on major unresolved questions, important
      controversies, and future directions in the field. Finally, career development
      activities provided mentoring for trainees and junior investigators, and
      networking opportunities for those individuals with established researchers in
      the field. Overall, the meeting was rated as a success by attendees and covered a
      wide range of lively and provocative discussion topics on the changing nature of
      the field of "kisspeptinology" and its future. This article is protected by
      copyright. All rights reserved.

PMID- 29656509
TI  - Melioration revisited: a systematic replication of Vaughan (1981).
AB  - Organisms that behave so as to forfeit a relatively higher overall rate of
      reinforcement in favor of a relatively lower rate are said to engage in
      suboptimal choice. Suboptimal choice has been linked with maladaptive behavior in
      humans. Melioration theory offers one explanatory framework for suboptimal
      choice. Melioration theory suggests behavior is controlled by differences in
      local reinforcer rates between alternatives. Vaughan (1981) arranged two
      experimental conditions in which maximizing the overall rate of reinforcement
      required behavior that was compatible, or incompatible, with melioration. Vaughan
      found pigeons allocated more time to a locally richer alternative even when doing
      so resulted in suboptimal choice. However, Vaughan did not show whether these
      effects could systematically reverse and did not provide within-session data to
      show that choice across short time spans remains under the control of differences
      in local reinforcer rates. The present study used pigeons to replicate and extend
      Vaughan's findings. We investigated shifts in overall- and within-session choice
      across repeated conditions, according to arranged local contingencies. Behavior
      systematically followed changes in local contingencies for most pigeons. Within
      session data suggests that, providing differences in local reinforcer rates are
      discriminated, pigeons will allocate more time to a locally richer alternative,
      even if this leads to suboptimal choice. These findings facilitate the more
      confident use of similar procedures that investigate how melioration contributes
      to suboptimal choice.

PMID- 29656510
TI  - Robust motion correction in CEST imaging exploiting low-rank approximation of the
      z-spectrum.
AB  - PURPOSE: To introduce and evaluate an image registration technique for robust
      quantification of CEST acquisitions corrupted by motion. METHODS: The proposed
      iterative algorithm exploits a low-rank approximation of the z-spectrum (LRAZ),
      to gradually separate the contrast variation due to saturation at different off
      resonance frequencies and accompanying motion. This registration method was first
      tested in a creatine CEST analysis of a phantom with simulated rigid motion.
      Subsequently, creatine CEST acquisitions in the human thigh during exercise were
      exemplarily corrected. RESULTS: The z-spectrum obtained by applying LRAZ to the
      corrupted phantom series exhibited a normalized RMS error with respect to the
      noncorrupted gold standard series of less than 4%. The corresponding creatine map
      resulting from an asymmetry analysis of the registered data showed only little
      difference with regard to the noncorrupted determination, too. A comparable
      performance was observed exploiting LRAZ for the correction of nonrigid motion
      within the dynamic CEST acquisitions in skeletal muscles. While for the phantom
      simulations, high-quality registration was also possible by using a single
      reference image for the whole series and mutual information as similarity metric,
      this conventional approach resulted in inappropriate correction of the more
      complicated motion of the human thigh. CONCLUSION: The newly introduced method
      allows for a robust registration of CEST image series, which are corrupted by
      rigid and nonrigid motion of the investigated organ. The technique therefore
      improves the diagnostic value in various applications of CEST.

PMID- 29656511
TI  - Neuropathic pain: A patient-centred approach to measuring outcomes.
AB  - BACKGROUND: Neuropathic pain (NP) is a complex, chronic pain state initiated by a
      primary lesion or dysfunction of the nervous system and presents as a variety of
      symptoms across multiple disease states. OBJECTIVE: To develop a patient-centred
      conceptual model of symptoms and impacts in subjects with diabetic peripheral
      neuropathy (DPN) or post-herpetic neuralgia (PHN) that can inform the measurement
      strategy in clinical trials. METHOD: Thirty subjects with DPN or PHN participated
      in in-person interviews which were performed until saturation was achieved.
      Transcripts were analysed in ATLAS.ti. RESULTS: Interviews were completed with
      DPN subjects (United States, n = 10; Japan, n = 10) and PHN subjects (United
      States, n = 5; Japan, n = 5). Numbness and tingling were frequently reported
      symptoms in the DPN population while itchiness and hypersensitivity were
      predominant in PHN. Both populations experienced burning and ache/soreness with
      similar frequency. DPN subjects experienced pain primarily in their lower
      extremity (eg feet, ankles), while PHN subjects experienced pain primarily in the
      chest and back. Impacts reported by DPN subjects included difficulty walking,
      sleep disturbance and climbing stairs. Impacts in PHN subjects included sleep
      disturbance, avoidance of physical contact, being angry/frustrated and being
      sad/depressed. Overall, concepts in Japan were not qualitatively different from
      the United States. Conceptual models of NP were generated based on the concepts
      elicited. CONCLUSIONS: This research highlights core concepts to measure from the
      patient's perspective. Moreover, it enables the assessment of existing measures,
      the possible modification of these measures, or if a new NP measure with improved
      sensitivity and responsiveness is merited.

PMID- 29656512
TI  - Procalcitonin; a feasible biomarker for severe bacterial infections in Obstetrics
      and Gynecology?

PMID- 29656513
TI  - Acidic and alkaline chemicals' influence on a tricalcium silicate-based dental
      biomaterial.
AB  - Bioactive hydraulic tricalcium silicate materials are commonly used in several
      dental procedures. Mineral Trioxide Aggregate (MTA) is one such material, which
      is used in a variety of clinical applications, the most recent of which is root
      canal sealing material, during which, the MTA potentially comes in contact with
      remnants of the chemical agents used for disinfecting root canals. The effects of
      commonly used root canal irrigating solutions on MTA have not been investigated
      in depth, thus far. The aim of this study was to determine the effect of five
      common chemical agents used in root canal preparation (sodium hypochlorite/NaOCl,
      ethylene diaminetetraacetic acid/EDTA, mixture of sodium hypochlorite and
      etidronic acid/NaOCl + EA, mixture of EDTA and Chlorhexidine/QMix, or saline) on
      a commercial tricalcium silicate (MTA Plus). Samples were analyzed using scanning
      electron microscopy with energy dispersive spectroscopy, X-ray Diffraction (XRD),
      Fourier Transform Infrared Spectroscopy and Inductively coupled plasma techniques
      to see effects of phases formed and calcium ion release. Specimens immersed in
      NaOCl and NaOCl + EA had strong peaks for calcium hydroxide, but materials
      exposed to EDTA and QMix had lesser XRD peaks for calcium hydroxide. The calcium
      hydroxide peak in the XRD indicates hydration of tricalcium silicate and
      formation of amorphous calcium silicate hydrate. Calcium released from samples
      immersed in EDTA and NaOCl was less than in NaOCl + EA and QMix solutions. Fewer
      calcium phosphate crystals and less calcium hydroxide were observed with the
      samples in NaOCl, EDTA and QMix, which could have an important impact as it
      negatively influences the bioactivity. (c) 2018 Wiley Periodicals, Inc. J Biomed
      Mater Res Part B: Appl Biomater, 2018.

PMID- 29656514
TI  - Microbial diversity and biomarker analysis of modern freshwater microbialites
      from Laguna Bacalar, Mexico.
AB  - Laguna Bacalar is a sulfate-rich freshwater lake on the Yucatan Peninsula that
      hosts large microbialites. High sulfate concentrations distinguish Laguna Bacalar
      from other freshwater microbialite sites such as Pavilion Lake and Alchichica,
      Mexico, as well as from other aqueous features on the Yucatan Peninsula. While
      cyanobacterial populations have been described here previously, this study offers
      a more complete characterization of the microbial populations and corresponding
      biogeochemical cycling using a three-pronged geobiological approach of
      microscopy, high-throughput DNA sequencing, and lipid biomarker analyses. We
      identify and compare diverse microbial communities of Alphaproteobacteria,
      Deltaproteobacteria, and Gammaproteobacteria that vary with location along a bank
      to-bank transect across the lake, within microbialites, and within a neighboring
      mangrove root agglomeration. In particular, sulfate-reducing bacteria are
      extremely common and diverse, constituting 7%-19% of phylogenetic diversity
      within the microbialites, and are hypothesized to significantly influence
      carbonate precipitation. In contrast, Cyanobacteria account for less than 1% of
      phylogenetic diversity. The distribution of lipid biomarkers reflects these
      changes in microbial ecology, providing meaningful biosignatures for the microbes
      in this system. Polysaturated short-chain fatty acids characteristic of
      cyanobacteria account for <3% of total abundance in Laguna Bacalar microbialites.
      By contrast, even short-chain and monounsaturated short-chain fatty acids
      attributable to both Cyanobacteria and many other organisms including types of
      Alphaproteobacteria and Gammaproteobacteria constitute 43%-69% and 17%-25%,
      respectively, of total abundance in microbialites. While cyanobacteria are the
      largest and most visible microbes within these microbialites and dominate the
      mangrove root agglomeration, it is clear that their smaller, metabolically
      diverse associates are responsible for significant biogeochemical cycling in this
      microbialite system.

PMID- 29656515
TI  - Comparative CYP-omic analysis between the DDT-susceptible and -resistant
      Drosophila melanogaster strains 91-C and 91-R.
AB  - BACKGROUND: Cytochrome P450 monooxygenases (P450s) are involved in the
      biosynthesis of endogenous intracellular compounds and the metabolism of
      xenobiotics, including chemical insecticides. We investigated the structural and
      expression level variance across all P450 genes with respect to the evolution of
      insecticide resistance under multigenerational dichlorodiphenyltrichloroethane
      (DDT) selection. RESULTS: RNA-sequencing (RNA-seq) and reverse transcriptase
      quantitative polymerase chain reaction (RT-qPCR) indicated that the transcript
      levels of seven P450 genes were significantly up-regulated and three P450 genes
      were down-regulated in the DDT-resistant strain 91-R, as compared to the control
      strain 91-C. The overexpression of Cyp6g1 was associated with the presence of an
      Accord and an HMS-Beagle element insertion in the 5' upstream region in
      conjunction with copy number variation in the 91-R strain, but not in the 91-C
      strain. A total of 122 (50.2%) fixed nonsynonymous (amino acid-changing)
      mutations were found between 91-C and 91-R, and 20 (8.2%) resulted in amino acid
      changes within functional domains. Three P450 proteins were truncated as a result
      of premature stop codons and fixed between strains. CONCLUSION: Our results
      demonstrate that a combination of changes in P450 protein-coding regions and
      transcript levels are possibly associated with DDT resistance, and thereby
      suggest that selection for variant function may occur within this gene family in
      response to chronic DDT exposure. (c) 2018 Society of Chemical Industry.

PMID- 29656516
TI  - MiR-21 ameliorates age-associated skin wound healing defects in mice.
AB  - BACKGROUND: The cellular and molecular mechanisms responsible for the age
      associated delay of cutaneous wound healing are still not well understood.
      Previous studies have shown that miR-21 plays key roles during skin wound
      healing. We presumed that dysregulation of miR-21 may be involved in age
      associated defects in wound healing and that miR-21 may be one potential
      therapeutic target by which to ameliorate wound defects in elderly subjects.
      METHODS: Circular full thickness excisional wounds were made on the dorsal skin
      of young (2-month-old) and aged (12-month-old) female mice. The wound healing
      rates were quantified and compared between wild-type and miR-21 knock-in mice.
      Both histologic and morphometric analyses of the wounds were evaluated.
      Furthermore, the expression patterns of miR-21 during wound healing in both young
      and aged mice were assessed by in situ hybridization. The effects of topical miR
      21 overexpression on wound healing in aged mice were estimated by both wound
      closure quantification and histological analyses. RESULTS: Aged miR-21 knock-in
      female mice showed significantly improved wound healing compared to their wild
      type counterparts with respect to mature granulation tissue, smaller wound width
      and thinner epidermis. The expression patterns of miR-21 showed that miR-21
      levels were insufficient for repairing granulation tissue in aged mice.
      Intradermal injection of miR-21 plasmid around wounds could upregulate miR-21
      levels during wound healing and ameliorate age-associated skin wound defects.
      CONCLUSIONS: The results of the present study reveal that the upregulation of miR
      21 levels could improve wound repair in aged mice, which suggests that a
      therapeutic strategy targeting miR-21 expression in age-associated wound healing
      may be feasible.

PMID- 29656517
TI  - A Color-Tunable Fluorescent Supramolecular Hyperbranched Polymer Constructed by
      Pillar[5]arene-Based Host-Guest Recognition and Metal Ion Coordination
      Interaction.
AB  - Fluorescent supramolecular polymers are an important kind of smart material. In
      this work, a new fluorescent supramolecular hyperbranched polymer (FSHP) is
      constructed by orthogonal self-assembly: pillararene-based host-guest interaction
      and metal ion complexation interaction. The FSHP exhibits concentration
      controllable fluorescence emissions. The photoluminescence spectra and light
      emitting colors of FSHP can be effectively tuned by changing metal ion types or
      using mixed metal ions. The fluorescence quenching of FSHP solutions or FSHP
      based films would occur when removing the metal ions from the backbone of FSHP.
      This study supplies a convenient approach toward the construction of structure
      tunable fluorescent supramolecular materials with different colors.

PMID- 29656518
TI  - Genotype-specific progression of hereditary medullary thyroid cancer.
AB  - Although already 25 years into the genomic era, age-related progression of
      hereditary medullary thyroid cancer (MTC), the prevalence of which is estimated
      at one in 80,000 inhabitants, remains to be delineated for most unique RET
      (REarranged during Transfection) mutations. Included in this study were 567 RET
      carriers. The age-related progression of MTC across histopathological groups
      (normal thyroid/C-cell hyperplasia; node-negative MTC; node-positive MTC) was
      statistically significant for 13 unique RET mutations (p.Cys611Phe/c.1832G > T;
      p.Cys611Tyr; p.Cys618Ser/c.1852T > A; p.Cys620Arg; p.Cys634Arg; p.Cys634Phe;
      p.Cys634Ser; p.Cys634Tyr; p.Glu768Asp; p.Leu790Phe/c.2370G > T; p.Val804Met;
      p.Ser891Ala; p.Met918Thr), whereas two unique RET mutations (p.Cys618Phe;
      p.Cys634Gly) trended toward statistical significance. When grouped by mutational
      risk (highest; high; moderate-high; low-moderate; polymorphism), the age-related
      progression of MTC was significant for all four categories of RET mutations,
      which differed significantly across and within the three histopathological
      groups. For high, for moderate-high, and for low-moderate risk RET mutations, the
      age-related progression of MTC by mutated codon was broadly comparable across and
      within the three histopathological groups, and essentially unaffected by the
      amino acid substitutions examined. These data argue in favor of splitting the
      American Thyroid Association's moderate-risk category into moderate-high and low
      moderate risk categories, while emphasizing the need to contradistinguish the
      latter from rare nonpathogenic polymorphisms.

PMID- 29656519
TI  - Character evolution and missing (morphological) data across Asteridae.
AB  - PREMISE OF THE STUDY: Our current understanding of flowering plant phylogeny
      provides an excellent framework for exploring various aspects of character
      evolution through comparative analyses. However, attempts to synthesize this
      phylogenetic framework with extensive morphological data sets have been
      surprisingly rare. Here, we explore character evolution in Asteridae (asterids),
      a major angiosperm clade, using an extensive morphological data set and a well
      resolved phylogeny. METHODS: We scored 15 phenotypic characters (spanning
      chemistry, vegetative anatomy, and floral, fruit, and seed features) across 248
      species for ancestral state reconstruction using a phylogenetic framework based
      on 73 plastid genes and the same 248 species. KEY RESULTS: Iridoid production,
      unitegmic ovules, and cellular endosperm were all reconstructed as synapomorphic
      for Asteridae. Sympetaly, long associated with asterids, shows complex patterns
      of evolution, suggesting it arose several times independently within the clade.
      Stamens equal in number to the petals is likely a synapomorphy for Gentianidae, a
      major asterid subclade. Members of Lamianae, a major gentianid subclade, are
      potentially diagnosed by adnate stamens, unilacunar nodes, and simple perforation
      plates. CONCLUSIONS: The analyses presented here provide a greatly improved
      understanding of character evolution across Asteridae, highlighting multiple
      characters potentially synapomorphic for major clades. However, several important
      parts of the asterid tree are poorly known for several key phenotypic features
      (e.g., degree of petal fusion, integument number, nucellus type, endosperm type,
      iridoid production). Further morphological, anatomical, developmental, and
      chemical investigations of these poorly known asterids are critical for a more
      detailed understanding of early asterid evolution.

PMID- 29656520
TI  - First Attempt of Glycidol-to-Monoalkyl Glyceryl Ethers Conversion by Acid
      Heterogeneous Catalysis: Synthesis and Simplified Sustainability Assessment.
AB  - The selective preparation of monoalkylglyceryl ethers (MAGEs) is a task for
      researchers owing to their broad range of applications. In this work, green
      feedstocks such as glycidol and alcohols were used to prepare MAGEs under mild
      reaction conditions (80  degrees C, 3 h, 0.5 mol % catalyst) in the presence of
      acid heterogeneous catalysts. Nafion shows the best performances in terms of
      conversion and selectivity to MAGES and also high stability. A comparison of the
      environmental performances with the most consolidated pathway from glycerol has
      shown that the usage of glycidol (recovered as a value-added product from
      Epicerol process) and Nafion leads to a lower impact on ecosystems. In addition,
      results achieved from a simplified socio-economic analysis show that the
      innovative route here proposed has potential (at the laboratory scale) of
      enhancing potential gains and of reducing the social implications resulting from
      externalities associated with environmental impacts (e.g., CO2 equivalents).

PMID- 29656521
TI  - Resveratrol effect on patients with non-alcoholic fatty liver disease: A matter
      of dose and treatment length.

PMID- 29656522
TI  - Hybrid T2 - and T1 -weighted radial acquisition for free-breathing abdominal
      examination.
AB  - PURPOSE: Most clinical MR examinations require acquisition of different image
      contrasts. For abdominal exams, the scans are conventionally performed as
      separate acquisitions using respiratory gating or repeated breath holding, which
      can be time-inefficient and challenging for patients. Here, a hybrid imaging
      approach is described that creates T2 - and T1 -weighted images from a single
      scan and allows for free-breathing acquisition. THEORY AND METHODS: T2 -weighted
      data is collected using 3D fast spin-echo (FSE) acquisition with motion-robust
      radial stack-of-stars sampling. The wait time between the FSE trains is used to
      acquire T1 -weighted gradient-echo (GRE) data. Improved robustness is achieved by
      extracting a respiratory signal from the GRE data and using it for motion
      weighted reconstruction. RESULTS: As validated in simulations and phantom scans,
      GRE acquisition in the wait time has minor effect on the signal strength and
      contrast. Volunteer scans at 1.5T showed that T2 - and T1 -weighted hybrid
      imaging is feasible during free-breathing. Furthermore, it has been demonstrated
      in a patient that hybrid imaging with T1 -weighted Dixon acquisition is possible.
      CONCLUSION: The described hybrid sequence enables comprehensive T2 - and T1 
      weighted imaging in a single scan. In addition to free-breathing abdominal
      examination, it promises value for clinical applications that are frequently
      affected by motion artifacts.

PMID- 29656523
TI  - Parasitic wasp-associated symbiont affects plant-mediated species interactions
      between herbivores.
AB  - Microbial mutualistic symbiosis is increasingly recognised as a hidden driving
      force in the ecology of plant-insect interactions. Although plant-associated and
      herbivore-associated symbionts clearly affect interactions between plants and
      herbivores, the effects of symbionts associated with higher trophic levels has
      been largely overlooked. At the third-trophic level, parasitic wasps are a common
      group of insects that can inject symbiotic viruses (polydnaviruses) and venom
      into their herbivorous hosts to support parasitoid offspring development. Here,
      we show that such third-trophic level symbionts act in combination with venom to
      affect plant-mediated interactions by reducing colonisation of subsequent
      herbivore species. This ecological effect correlated with changes induced by
      polydnaviruses and venom in caterpillar salivary glands and in plant defence
      responses to herbivory. Because thousands of parasitoid species are associated
      with mutualistic symbiotic viruses in an intimate, specific relationship, our
      findings may represent a novel and widespread ecological phenomenon in plant
      insect interactions.

PMID- 29656524
TI  - The prevalence of meibomian gland dysfunction, tear film and ocular surface
      parameters in an Austrian dry eye clinic population.
AB  - PURPOSE: The purpose of this study was to assess the prevalence of meibomian
      gland dysfunction (MGD) and its association with tear film and ocular surface
      parameters in an Austrian clinical population of dry eye patients. METHODS: The
      records of 1372 consecutive patients from a dry eye unit were analysed
      retrospectively. Symptoms and objective tear film and ocular surface parameters
      were evaluated. Patients were classified into pure MGD, pure aqueous tear
      deficiency (ATD), MGD combined with ATD, pure anterior blepharitis (AB),
      Sjogren's syndrome (SS) without MGD and SS together with MGD. RESULTS: Nine
      hundred and sixty-five patients, that is 70.3% of the investigated population,
      mean age 55.4 +/- 16.6 years, had signs of MGD. Of these, 684 (70.9%) were
      female. The intensity of symptoms did not differ between subgroups. Four hundred
      and ninety (50.8%) MGD patients had Schirmer test values <=10 mm/5 min. The
      fluorescein break-up time and Schirmer test values were significantly higher in
      the pure AB and MGD group. The pure MGD group showed a significantly lower
      fluorescein staining of the cornea compared to the other groups, except for pure
      AB. Lissamine green staining of the ocular surface was present in all groups, but
      was at least pronounced in the pure MGD and AB group. CONCLUSION: Meibomian gland
      dysfunction is a major cause of ocular discomfort and could often be found in
      combination with a reduced aqueous tear secretion. Although the intensity of
      subjective complaints was similar to all other subgroups, pure MGD exhibited the
      lowest severity of signs of ocular surface damage and also affected younger
      people.

PMID- 29656525
TI  - Authors' reply re: Cardiorespiratory fitness, exercise haemodynamics and birth
      outcomes: the Coronary Artery Risk Development in Young Adults (CARDIA) Study.

PMID- 29656526
TI  - Access to knowledge and the Global Abortion Policies Database.
AB  - Research shows that women, healthcare providers, and even policy makers worldwide
      have limited or inaccurate knowledge of the abortion law and policies in their
      country. These knowledge gaps sometimes stem from the vague and broad terms of
      the law, which breed uncertainty and even conflict when unaccompanied by
      accessible regulation or guidelines. Inconsistency across national law and policy
      further impedes safe and evidence-based practice. This lack of transparency
      creates a crisis of accountability. Those seeking care cannot know their legal
      entitlements, service providers cannot practice with legal protection, and
      governments can escape legal responsibility for the adverse effects of their
      laws. This is the context for the newly launched Global Abortion Policies
      Database-an open-access repository that seeks to promote transparency and state
      accountability by providing clear and comprehensive information about national
      laws, policies, health standards, and guidelines, and by creating the capacity
      for comparative analysis and cross-referencing to health indicators, WHO
      recommendations, and human rights standards.

PMID- 29656527
TI  - Self-Assembly of Rod-Coil Block Copolymers on Carbon Nanotubes: A Route toward
      Diverse Surface Nanostructures.
AB  - In this work, it is reported that poly(gamma-benzyl-l-glutamate)-block
      poly(ethylene glycol) (PBLG-b-PEG) rod-coil block copolymers (BCPs) can disperse
      carbon nanotubes (CNTs) in solution and form various surface nanostructures on
      the CNTs via solution self-assembly. In an organic solvent that dissolves the
      BCPs, the PBLG rod blocks adsorb on CNT surfaces, and the BCPs form conformal
      coatings. Then, by the introduction of water, a selective solvent for PEG blocks,
      the BCPs in the coatings further self-assemble into diverse surface
      nanostructures, such as helices (left-handed or right-handed), gyros, spheres,
      and rings. The morphology of the surface nanostructure can be tailored by initial
      organic solvent composition, preparation temperature, feeding ratio of BCPs to
      CNTs, degree of polymerization of PBLG blocks, and diameter of the CNTs.

PMID- 29656528
TI  - The role of Scalpel-bougie cricothyroidotomy in managing emergency Front of Neck
      Airway access. A review and technical update for ENT surgeons.

PMID- 29656529
TI  - Residue transfer and risk assessment of carbendazim in tea.
AB  - BACKGROUND: Carbendazim (methyl 1H-benzimidazol-2-ylcarbamate) residue in tea is
      a public concern. The large gap in the maximum residue limits (MRLs) for
      carbendazim in tea makes it difficult to conduct pesticide management. Therefore,
      a systemic evaluation of the residue and the health risk of carbendazim from the
      tea garden to brewed tea was investigated. RESULTS: The dissipation of
      carbendazim in tea shoots followed first-order rate kinetics, with a half-life
      (t1/2 ) of 2.6 days. In green tea manufacturing, the carbendazim decrease of 2.81
      26.74% was concentration-positive. The infusion factor of carbendazim was > 0.8
      from dry tea to brewed tea and this was related to the brewing temperature and
      the size of the dry tea. All of the risk quotient values were significantly less
      than 1 in the evaluation of carbendazim residue in real tea samples and MRL.
      CONCLUSION: Residue transfer and risk assessment were evaluated for carbendazim
      in green tea. Carbendazim revealed a less persistent nature in tea plants. Green
      tea processing played a small role in decreasing carbendazim residue. Almost all
      of the carbendazim in dry tea leached into the brewed tea. However, the possible
      health risk induced by residual carbendazim in green tea was not significant.
      These findings are helpful when reconsidering the MRLs of carbendazim in tea. (c)
      2018 Society of Chemical Industry.

PMID- 29656530
TI  - Mycobacterium tuberculosis after solid organ transplantation: A review of more
      than 2000 cases.
AB  - BACKGROUND: Mycobacterium tuberculosis (TB) is a common pathogen worldwide, and
      it may cause significant infection after solid organ transplantation (SOT). We
      reviewed all reported TB cases to provide an update on its epidemiology, clinical
      presentation, management, and outcome after SOT. METHODS: MEDLINE, EMBASE, and
      OVID were reviewed from January 1, 1998, to December 31, 2016, using keywords
      tuberculosis and solid organ transplant or transplantation. RESULTS: There were
      187 publications reporting 2082 cases of TB among kidney (n = 1719), liver (n =
      253), heart (n = 77), lung (n = 25), and kidney-pancreas (n = 8) recipients.
      Among cohort studies, the median incidence was 2.37% (range, 0.05%-13.27%)
      overall. Most TB disease was considered reactivation of latent infection,
      occurring beyond the first year after SOT. Early-onset cases were seen among
      donor-derived TB cases. Fever was the most common symptom. Radiologic findings
      were highly variable. Extrapulmonary and disseminated TB occurred 29.84% and
      15.96%, respectively. Multidrug-resistant TB was rare. Treatment using 4 or 5
      drugs was commonly associated with hepatotoxicity and graft dysfunction. All
      cause mortality was 18.84%. CONCLUSIONS: This large review highlights the
      complexity of TB after SOT. Reactivation TB, donor-transmitted infection,
      extrapulmonary involvement, and disseminated disease are common occurrences.
      Treatment of TB is commonly associated with hepatotoxicity and graft dysfunction.

PMID- 29656531
TI  - Post-traumatic stress disorder and risk of osteoporosis: A nationwide
      longitudinal study.
AB  - Several studies suggested a relationship between stress and related mental
      illnesses, such as depression and osteoporosis. However, it was unclear whether
      patients with post-traumatic stress disorder (PTSD) were at risk of developing
      osteoporosis in later life. In this study, 6,041 patients with PTSD and 24,164
      age- or sex-matched controls were enrolled between 2002 and 2009 in our study and
      followed up to the end of 2011. Cases of osteoporosis were identified during the
      follow-up. Patients with PTSD had an elevated likelihood of developing
      osteoporosis (HR: 2.66, 95% CI [1.91, 3.71]) in later life compared with the
      controls. Sensitivity tests after excluding the first year observation (HR: 2.46,
      95% CI [1.72, 3.53]) and the first 3-year observation (HR: 1.88, 95% CI [1.18,
      3.01]) were consistent. Patients with PTSD had a higher risk of developing
      osteoporosis at an earlier age compared with those without PTSD. Further studies
      would be necessary to clarify the pathophysiology between PTSD and osteoporosis.

PMID- 29656532
TI  - Of lamp posts, keys, and fabled drunkards: A perspectival tale of 4 guidelines.
AB  - BACKGROUND: Evidence-based medicine is the application of research findings to
      inform individual clinical decisions. There is a tension-both philosophical and
      practical-between the average result from a population study and the
      circumstances and needs of an individual patient. This personal account of
      "evidence-based" trauma care illustrates and explores this tension. THE CASE: The
      author, a keen athlete, describes her experience of a high-impact cycle accident
      that led to limb fractures (which were diagnosed and treated according to
      evidence-based guidelines) and also an occult injury to the cervical spine (which
      was not diagnosed at the time). Some evidence-based guidelines are reviewed and
      applied to the case. The clinical record described the cycle accident as a
      "fall." Initial assessment directed the clinicians' gaze to the obvious injuries,
      whose treatment was straightforward. On admission, the patient (aged 55 years at
      the time) was offered "falls prevention" via a guideline-based checklist. Several
      months later, neurological sequelae indicated possible damage to the cervical
      spine. But the NICE Guideline recommending cervical spine imaging in cases of
      high-impact trauma had not been considered-perhaps because the clinical narrative
      had been prematurely assigned to the script of "older person with fall."
      Furthermore, the author, who was (appropriately) treated with neurosurgery, was
      surprised at the response of clinical colleagues, based on application of an
      irrelevant section of a guideline, that her cervical discectomy was "nonevidence
      based." Nonsteroidal anti-inflammatory drugs for postoperative pain were
      indicated in this patient even though they were not recommended for the average
      patient. CONCLUSION: As Sir John Grimley Evans' warned, we should avoid using
      evidence-based guidelines in the manner of the fabled drunkard who searched under
      the lamp post for his key because that was where the light was, even though he
      knew he had lost his key somewhere else.

PMID- 29656533
TI  - A weed resistance management game: a teaching tool.
AB  - BACKGROUND: This article provides instructions and materials to moderate an
      interactive resistance management game. The game is designed to generate
      discussion about the challenges and possibilities of coordinating resistance
      management activities among groups of farmers. The game has been successfully
      applied in classroom settings, extension workshops, and at professional weed
      science meetings. Research has found farmers often perceive the success of their
      own resistance management may be thwarted if their neighbors are not adequately
      managing resistance as well. This can lead to negative 'tragedy of the commons'
      outcomes. RESULTS: In past applications of the game exercise, participants have
      often responded in ways consistent with similar studies in experimental and
      behavioral economics. This includes dividing benefits evenly (even though this is
      not a requirement of the game) or treating one-time transactions as potentially
      repeated exchanges. Player behavior may also be greatly influenced by their
      attitudes toward monetary risks. CONCLUSION: The game allows participants to
      explore ways to overcome the tragedy of the commons and illustrates the roles of
      information sharing and economic incentives in finding solutions. It also allows
      participants to experiment with bottom-up voluntary approaches toward resistance
      management as an alternative to top-down regulatory approaches. (c) 2018 Society
      of Chemical Industry.

PMID- 29656535
TI  - Uterine and eggshell modifications associated with the evolution of viviparity in
      South American water snakes (Helicops spp.).
AB  - The evolution of viviparity requires eggshell thinning to bring together the
      maternal uterus and extraembryonic membranes to form placentae for physiological
      exchanges. Eggshell thinning likely involves reduced activity of the uterine
      glands that secrete it. We tested these hypotheses by comparing the uterine and
      eggshell structure and histochemistry among oviparous and viviparous water snakes
      (Helicops) using phylogenetic methods. Eggshell thinning occurred convergently in
      all three origins of viviparity in Helicops and was accomplished by the loss of
      the mineral layer and thinning of the shell membrane. Uterine glands secrete the
      shell membrane in both oviparous and viviparous Helicops. These glands increase
      during vitellogenesis regardless of the reproductive mode, but they always reach
      smaller sizes in viviparous forms. As there is no phylogenetic signal in eggshell
      thickness and gland dimensions, we conclude that interspecific differences are
      related to reproductive mode and not phylogeny. Therefore, our results support
      the hypothesis that eggshell thinning is associated with the evolution of
      viviparity and that such thinning result from a reduction in gland size in
      viviparous taxa. Interestingly, the shell membrane thickness of viviparous
      females of the reproductively bimodal Helicops angulatus is intermediate between
      their oviparous and viviparous congeners. Thus, although eggshell thinning is
      required by the evolution of viviparity, a nearly complete loss of this structure
      is not. However, uterine gland dimensions are similar across viviparous Helicops.
      Fewer glands or their functional repurposing may explain the thinner shell
      membrane in viviparous species of Helicops in comparison to viviparous females of
      the bimodal H. angulatus.

PMID- 29656537
TI  - Histological evaluation of the repair process of replanted rat teeth after
      storage in resveratrol dissolved in dimethyl sulphoxide.
AB  - BACKGROUND/AIM: The storage media is directly related to the prognosis of avulsed
      teeth, with resveratrol drawing attention due to its antioxidant and anti
      inflammatory proprieties. The aim of this study was to evaluate the repair
      process in rat teeth following delayed replantation after storage in resveratrol
      (R) dissolved in dimethyl sulphoxide (DMSO). MATERIALS AND METHODS: The upper
      right central incisors of 36 rats were divided into 4 groups. In group I, the
      teeth were extracted and immediately replanted. Group II teeth were stored in 50
      mL R+DMSO (0.0512 g/mL), whereas group III teeth were stored in 50 mL pure DMSO,
      both for a period of 60 minutes. The teeth of group IV were stored dry for 60
      minutes. The teeth of groups II, III and IV were then replanted, and the animals
      were euthanized after 60 days. Longitudinal histological cuts were HE stained for
      histomorphometric analysis of the periodontal ligament, alveolar bone, cementum
      and dentin. RESULTS: The analysis of HE stained histological sections showed the
      following statistical differences: the acute inflammatory process in the
      epithelial insertion was less prominent in group II than in group III; the
      organization of the periodontal ligament was better in group I, while the
      intensity and extension of acute inflammation in the periodontal ligament were
      better in group I, and worse in group III; the chronic inflammatory infiltrate
      was less in groups I and IV, and the depth and extent of resorption, as well as
      the repair of root resorption, were better in group I. CONCLUSIONS: Storage in
      R+DMSO solution did not inhibit root resorption after delayed replantation in rat
      teeth. It is concluded that pure DMSO is not a suitable transport medium for
      avulsed teeth.

PMID- 29656536
TI  - MMR Deficiency Does Not Sensitize or Compromise the Function of Hematopoietic
      Stem Cells to Low and High LET Radiation.
AB  - One of the major health concerns on long-duration space missions will be
      radiation exposure to the astronauts. Outside the earth's magnetosphere,
      astronauts will be exposed to galactic cosmic rays (GCR) and solar particle
      events that are principally composed of protons and He, Ca, O, Ne, Si, Ca, and Fe
      nuclei. Protons are by far the most common species, but the higher atomic number
      particles are thought to be more damaging to biological systems. Evaluation and
      amelioration of risks from GCR exposure will be important for deep space travel.
      The hematopoietic system is one of the most radiation-sensitive organ systems,
      and is highly dependent on functional DNA repair pathways for survival. Recent
      results from our group have demonstrated an acquired deficiency in mismatch
      repair (MMR) in human hematopoietic stem cells (HSCs) with age due to functional
      loss of the MLH1 protein, suggesting an additional risk to astronauts who may
      have significant numbers of MMR deficient HSCs at the time of space travel. In
      the present study, we investigated the effects gamma radiation, proton radiation,
      and 56 Fe radiation on HSC function in Mlh1+/+ and Mlh1-/- marrow from mice in a
      variety of assays and have determined that while cosmic radiation is a major risk
      to the hematopoietic system, there is no dependence on MMR capacity. Stem Cells
      Translational Medicine 2018;7:513-520.

PMID- 29656539
TI  - Confronting bias in health care.

PMID- 29656538
TI  - CD200 expression in flow cytometry helps to distinguish mantle cell lymphoma from
      other CD5-positive B-cell neoplasms.

PMID- 29656540
TI  - Management of pregnancy complications in type 2N von Willebrand disease
      associated to a novel mutation.

PMID- 29656541
TI  - A novel herpesvirus associated with chronic superficial keratitis and
      proliferative conjunctivitis in a great horned owl (Bubo virginianus).
AB  - An adult great-horned owl (Bubo virginianus; GHOW) presented with a history of
      recurrent corneal ulceration of the right eye (OD). Findings included ulcerative
      superficial keratitis, proliferative conjunctivitis, and iris pigmentary changes.
      The ulcer was initially nonresponsive to medical therapy, but showed rapid and
      appropriate healing following diamond burr debridement. Proliferative
      conjunctivitis markedly improved following topical antiviral therapy with
      cidofovir 1%, interferon alpha 2B ophthalmic solutions, and oral l-lysine.
      Histopathologic evaluation of a conjunctival biopsy revealed epithelial features
      suspicious for viral cytopathic changes and intranuclear structures suspicious
      for viral inclusions, suggestive of a possible viral-induced papillomatous
      conjunctivitis. A novel alphaherpesvirus, referred to as Strigid Herpesvirus 1
      (StrHV1), was identified using PCR and gene sequencing. This case represents a
      new clinical manifestation of a previously unreported herpesvirus in the GHOW.
      Identification of the herpes virus was critical to administration of appropriate
      therapy and resolution of the conjunctivitis, and corneal epithelial debridement
      promoted resolution of the chronic corneal epithelial defect.

PMID- 29656542
TI  - Evaluation of permeability and fluid wicking in woven fiber bone scaffolds.
AB  - Research characterizing transport of nutrients and waste in tissue engineering
      scaffolds has led to the study of scaffold properties that contribute to
      permeability and porosity of the scaffold. Both permeability and porosity
      contribute to the transport properties of the scaffold; however, permeability
      relates to the degree to which pores are interconnected within the scaffold. This
      work evaluated permeability for woven polymer fiber scaffolds by modulating the
      following scaffold parameters: material combination, weave configuration, and
      fiber geometry. Materials tested were poly-l-lactide and poly-l-lactide-co-E
      caprolactone in various combinations. Plain and crowfoot weave configurations
      were compared, and grooved wicking fibers were compared with round cross-section
      fibers to study fiber geometry. A modification of the constant head hydraulic
      conductivity test was used in combination with a vertical wicking test to
      determine levels of permeability of the woven scaffolds. Results showed a
      significant effect on permeability for combinations of weave configuration, fiber
      geometry, and material combination. However, modulating fiber geometry
      demonstrated the most significant contribution to permeability. This result
      suggests the grooved wicking geometry may be used in scaffold development to
      regulate transport by selectively moving fluid away or toward the area of
      interest by capillary action. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res
      Part B: Appl Biomater, 2018.

PMID- 29656543
TI  - Diastereoselective Synthesis of Highly Substituted, Amino- and Pyrrolidino
      Tetrahydrofurans as Lead-Like Molecular Scaffolds.
AB  - A series of highly substituted tetrahydrofurans (THFs), decorated with modifiable
      2-aryl, 3-carboxy and 4-amino substituents, has been prepared for biological
      evaluation within the European Lead Factory. Diastereoselective reductive
      amination of pre-functionalised 4-oxofurans, readily prepared from cinnamate
      esters via oxa-Michael/Dieckmann annulation, provided the requisite THF cores on
      gram scale with three contiguous stereocentres, including full substitution at C
      3. In a second series, a pyrrolidine ring was fused to the same oxofuran scaffold
      via an intramolecular reductive amination, inverting the configuration at C-4
      relative to the other ring substituents. The resulting compounds, which displayed
      desirable physical properties as lead-like scaffolds, were derivatised into a
      small library of 24 compounds, demonstrating their ability to serve as starting
      points for drug discovery. Ultimately, this chemistry enabled the preparation of
      1948 THF-containing compounds for inclusion in the Joint European Compound
      Library.

PMID- 29656544
TI  - An overview on the identification of MAIT cell antigens.
AB  - Mucosal associated invariant T (MAIT) cells are restricted by the monomorphic MHC
      class I-like molecule, MHC-related protein-1 (MR1). Until 2012, the origin of the
      MAIT cell antigens (Ags) was unknown, although it was established that MAIT cells
      could be activated by a broad range of bacteria and yeasts, possibly suggesting a
      conserved Ag. Using a combination of protein chemistry, mass spectrometry,
      cellular biology, structural biology and small molecule chemistry, we discovered
      MR1 ligands derived from folic acid (vitamin B9) and from an intermediate in the
      microbial biosynthesis of riboflavin (vitamin B2). While the folate derivative 6
      formylpterin generally inhibited MAIT cell activation, two riboflavin pathway
      derivatives, 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil and 5-(2
      oxoethylideneamino)-6-D-ribitylaminouracil, were potent MAIT cell agonists. Other
      intermediates and derivatives of riboflavin synthesis displayed weak or no MAIT
      cell activation. Collectively, these studies revealed that in addition to peptide
      and lipid-based Ags, small molecule natural product metabolites are also ligands
      that can activate T cells expressing alphabeta T-cell receptors, and here we
      recount this discovery.

PMID- 29656545
TI  - A framework for treating DSM-5 alternative model for personality disorder
      features.
AB  - Despite its demonstrated empirical superiority over the DSM-5 Section 2
      categorical model of personality disorders for organizing the features of
      personality pathology, limitations remain with regard to the translation of the
      DSM-5 Section 3 alternative model of personality disorders (AMPD) to clinical
      practice. The goal of this paper is to outline a general and preliminary
      framework for approaching treatment from the perspective of the AMPD. Specific
      techniques are discussed for the assessment and treatment of both Criterion A
      personality dysfunction and Criterion B maladaptive traits. A concise and step-by
      step model is presented for clinical decision making with the AMPD, in the hopes
      of offering clinicians a framework for treating personality pathology and
      promoting further research on the clinical utility of the AMPD. Copyright (c)
      2018 John Wiley & Sons, Ltd.

PMID- 29656546
TI  - A Guide to IL-1 family cytokines in adjuvanticity.
AB  - Growing awareness of the multiplicity of roles for the IL-1 family in immune
      regulation has prompted research exploring these cytokines in the context of
      vaccine-induced immunity. While tightly regulated, cytokines of the IL-1 family
      are normally released in response to cellular stress and in combination with
      other danger-/damage-associated molecular patterns (DAMPs), triggering potent
      local and systemic immune responses. In the context of infection or autoimmunity,
      engagement of IL-1 family receptors links robust innate responses to adaptive
      immunity. Clinical and experimental evidence has revealed that many vaccine
      adjuvants induce the release of one or multiple IL-1 family cytokines. The
      coordinated release of IL-1 family members in response to adjuvant-induced damage
      or cell death may be a determining factor in the transition from local
      inflammation to the induction of an adaptive response. Here, we analyse the
      effects of IL-1 family cytokines on innate and adaptive immunity with a
      particular emphasis on activation of antigen-presenting cells and induction of T
      cell-mediated immunity, and we address in detail the contribution of these
      cytokines to the modes of action of vaccine adjuvants including those currently
      approved for human use.

PMID- 29656547
TI  - Prenatal Sonographic Depiction of Large Intra-amniotic Umbilical Vein Thrombosis.

PMID- 29656548
TI  - Effects of geranylgeranylacetone upon cardiovascular diseases.
AB  - Heat shock proteins (HSPs) are an important family of protective proteins. They
      are involved actively in an array of cellular processes, including protective
      effects on the cardiovascular system in response to various stimuli. Increasing
      evidence shows that pharmacologic interventions that induce expression of HSPs
      may be a novel approach for the treatment of cardiovascular diseases. However,
      agents that induce expression of HSPs used previously are toxic or have harmful
      side effects, which limit their clinical application. Geranylgeranylacetone (GGA)
      is not only a widely used antiulcer agent in Asia, but also a nontoxic inducer of
      HSPs expression. It increases the expression of HSPs rapidly in the presence of
      ischemia, anoxia, oxidative stress, and toxicants, thereby having significant
      protective effects. The cardioprotective effects of GGA have been corroborated by
      experiments in vivo and in vitro. Importantly, several derivatives of GGA have
      been synthesized that have improved pharmaco-chemical and HSPs-boosting
      properties. In this review, the current knowledge and potential cardioprotective
      mechanisms of GGA are summarized comprehensively. We discuss the protective
      effects of GGA in cardiovascular diseases and myocardial injury induced by
      physical or chemical injury. Currently available information suggests that GGA
      could be employed as a novel pharmacologic intervention against cardiovascular
      disease.

PMID- 29656549
TI  - Sodium nitroprusside is effective in preventing and/or reversing the development
      of schizophrenia-related behaviors in an animal model: The SHR strain.
AB  - AIMS: The treatment of schizophrenia with antipsychotics is still unsatisfactory.
      Therefore, the search for new treatments and prevention is crucial, and animal
      models are fundamental tools for this objective. Preclinical and clinical data
      evidence the antipsychotic profile of sodium nitroprusside (SNP), a nitric oxide
      (NO) donor. We aimed to investigate SNP in treating and/or preventing the
      schizophrenia-related behaviors presented by the spontaneously hypertensive rats
      (SHR) strain. METHODS: Wistar rats (WR) and SHRs were submitted to two schemes of
      treatment: (i) a single injection of SNP or vehicle in adulthood; (ii) a long
      term early treatment from 30 to 60 postnatal day with SNP or vehicle. The
      following behaviors were evaluated 24 hours after the acute treatment or 30 days
      after the long-term treatment: locomotion, social interaction, and contextual
      fear conditioning. RESULTS: Spontaneously hypertensive rats presented
      hyperlocomotion, decreased social interaction, and impaired contextual fear
      conditioning. Single injection of SNP decreased social interaction in both
      strains and induced a deficit in contextual fear conditioning in WR. Oppositely,
      early treatment with SNP prevented the behavioral abnormalities in adult SHRs
      without promoting any effects in WR. CONCLUSION: Our preclinical data point to
      SNP as a preventive and safe strategy with a broad range of effectiveness to the
      positive, negative, and cognitive symptoms of schizophrenia.

PMID- 29656550
TI  - miR-181c-BRK1 axis plays a key role in actin cytoskeleton-dependent T cell
      function.
AB  - MicroRNAs are short endogenous noncoding RNAs that play pivotal roles in a
      diverse range of cellular processes. The miR-181 family is important in T cell
      development, proliferation, and activation. In this study, we have identified
      BRK1 as a potential target of miR-181c using a dual selection functional assay
      and have showed that miR-181c regulates BRK1 by translational inhibition. Given
      the importance of miR-181 in T cell function and the potential role of BRK1 in
      the involvement of WAVE2 complex and actin polymerization in T cells, we
      therefore investigated the influence of miR-181c-BRK1 axis in T cell function.
      Stimulation of PBMC derived CD3+ T cells resulted in reduced miR-181c expression
      and up-regulation of BRK1 protein expression, suggesting that miR-181c-BRK1 axis
      is important in T cell activation. We further showed that overexpression of miR
      181c or suppression of BRK1 resulted in inhibition of T cell activation and actin
      polymerization coupled with defective lamellipodia generation and immunological
      synapse formation. Additionally, we found that BRK1 silencing led to reduced
      expressions of other proteins in the WAVE2 complex, suggesting that the
      impairment of T cell actin dynamics was a result of the instability of the WAVE2
      complex following BRK1 depletion. Collectively, we demonstrated that miR-181c
      reduces BRK1 protein expression level and highlighted the important role of miR
      181c-BRK1 axis in T cell activation and actin polymerization-mediated T cell
      functions.

PMID- 29656551
TI  - Efficacy of three different steamers for control of bed bugs (Cimex lectularius
      L.).
AB  - BACKGROUND: Bed bugs, Cimex lectularius L., have become one of the most difficult
      urban pests to control. Steam treatment is reported to be an effective method to
      kill bed bugs and is considered to be an important component of bed bug
      integrated pest management (IPM). We evaluated and compared the efficacies of two
      affordable consumer-grade commercial steamers and a commonly used professional
      grade steamer for killing bed bugs. RESULTS: In laboratory experiments, the
      consumer-grade steamers at affordable prices achieved the same high control
      efficacy as the professional-grade steamer for treating bed bugs exposed on
      mattresses (100% bed bug mortality for all steamers), located beneath a fabric
      cover (>89% bed bug mortality for all steamers), or hiding in cracks (100% bed
      bug mortality for all steamers). Bed bugs located behind a leather cover did not
      suffer significant mortality from steam treatment regardless of the type of
      steamers used and the treatment duration. CONCLUSION: Proper use of steamers can
      kill all life stages of bed bugs. Affordable consumer-grade steamers are as
      effective as professional-grade steam machines for eliminating bed bugs resting
      on mattresses and hiding behind fabric materials or in cracks. (c) 2018 Society
      of Chemical Industry.

PMID- 29656552
TI  - Better performance of four-dimension computed tomography as a localization
      procedure in normocalcemic primary hyperparathyroidism.
AB  - INTRODUCTION: The multi-phase or four-dimensional computed tomography (4D CT) has
      emerged as a promising technique for preoperative localization of parathyroid
      lesions in patients with primary hyperparathyroidism (PHPT), but little is known
      about its accuracy in patients with normocalcemic primary hyperparathyroidism
      (NPHPT). METHODS: A total of 18 patients diagnosed with PHPT underwent three
      methods of preoperative localization (4D CT, TC-99-Sestamibi scintigraphy and
      ultrasonography). After surgery, the results of imaging were compared with
      operative findings, pathological and biochemical data to evaluate the sensitivity
      and of each localization procedure. RESULTS: In NPHPT the sensitivity for
      identifying the parathyroid lesion, according to presentation of PHPT
      (hypercalcemic or normocalcemic), was better with 4DCT in comparison to USG and
      scintigraphy. In these patients, the sensitivity for lateralization was as
      follows: USG: 22% (95% CI 0-44.9), scintigraphy: 11.1% (95% CI 0-31.6), 4DCT:
      55.6% (95% CI 23.1-88). In hypercalcemic patients the results were as follows:
      USG: 58.3% (95% CI 30.4-86.2), scintigraphy: 75% (95% CI 50.5-99.5), 4DCT: 75%
      (95% CI 50.5-99.5). There was a poor agreement between the three procedures in
      the identification of the parathyroid lesions, with Kappa coeficients of 0.292
      and 0.01 for scintigraphy and 4DCT, respectively, in comparison to USG.
      CONCLUSION: Our data showed that 4DCT had a better performance as a preoperative
      localization procedure of the parathyroid lesion in patients with NPHPT.

PMID- 29656553
TI  - Rational Fabrication of Anti-Freezing, Non-Drying Tough Organohydrogels by One
      Pot Solvent Displacement.
AB  - Tough hydrogels, polymeric network structures with excellent mechanical
      properties (such as high stretchability and toughness), are emerging soft
      materials. Despite their remarkably mechanical features, tough hydrogels exhibit
      two flaws (freezing around the icing temperatures of water and drying under arid
      conditions). Inspired by cryoprotectants (CPAs) used in the inhibition of the
      icing of water in biological samples, a versatile and straightforward method is
      reported to fabricate extreme anti-freezing, non-drying CPA-based organohydrogels
      with long-term stability by partially displacing water molecules within the pre
      fabricated hydrogels. CPA-based Ca-alginate/polyacrylamide (PAAm) tough hydrogels
      were successfully fabricated with glycerol, glycol, and sorbitol. The CPA-based
      organohydrogels remain unfrozen and mechanically flexible even up to -70  degrees
      C and are stable under ambient conditions or even vacuum.

PMID- 29656554
TI  - A single day of bed rest, irrespective of energy balance, does not affect
      skeletal muscle gene expression or insulin sensitivity.
AB  - NEW FINDINGS: What is the central question of this study? What are the initial
      metabolic and molecular events that underpin bed rest-induced skeletal muscle
      deconditioning, and what is the contribution of energy balance? What is the main
      finding and its importance? A single day of bed rest, irrespective of energy
      balance, did not lead to overt changes in skeletal muscle gene expression or
      insulin sensitivity. More than 1 day of physical inactivity is required to
      observe the insulin resistance and robust skeletal muscle transcriptional
      responses associated with bed rest and consequent alterations in energy balance.
      ABSTRACT: The initial metabolic and molecular events that underpin disuse-induced
      skeletal muscle deconditioning, and the contribution of energy balance, remain to
      be investigated. Ten young, healthy men (age 25 +/- 1 years; body mass index 25.3
      +/- 0.8 kg.m-2 ) underwent three 24 h laboratory-based experimental periods in a
      randomized, crossover manner: (i) controlled habitual physical activity with an
      energy-balanced diet (CON); (ii) strict bed rest with a diet to maintain energy
      balance (BR-B); and (iii) strict bed rest with a diet identical to CON,
      consequently resulting in positive energy balance. Continuous glucose monitoring
      was performed throughout each visit, with vastus lateralis muscle biopsies and an
      oral glucose tolerance test performed before and after. In parallel with muscle
      samples collected from a previous 7 day bed rest study, biopsies were used to
      examine the expression of genes associated with the regulation of muscle mass and
      insulin sensitivity. A single day of bed rest, irrespective of energy balance,
      did not lead to overt changes in whole-body substrate oxidation, indices of
      insulin sensitivity [i.e. homeostatic model assessment of insulin resistance, BR
      B from 2.7 +/- 1.7 to 3.1 +/- 1.5 (P > 0.05) and Matsuda index, BR-B from 5.9 +/-
      3.3 to 5.2 +/- 2.9 (P > 0.05)] or 24 h glycaemic control/variability compared
      with CON. Seven days of bed rest led to ~30-55% lower expression of genes
      involved in insulin signalling, lipid storage/oxidation and muscle protein
      breakdown, whereas no such changes were observed after 1 day of bed rest. In
      conclusion, more than a single day of physical inactivity is required to observe
      the insulin resistance and robust skeletal muscle transcriptional responses
      associated with bed rest and consequent alterations in energy balance.

PMID- 29656555
TI  - Bibbidi bobbidi bald: Two "hairowing" tales of Princess Package hairstyles.
AB  - We present cases of localized alopecia on the vertex scalp of two girls after
      elaborate professional hairstyling marketed as the "Princess Package" at a major
      U.S. theme park. Localized alopecia followed pain, erythema, and delayed crusting
      due to necrosis of the scalp. The majority of the affected alopecic areas had
      evidence of regrowth at interval follow-up, but small areas of scarring alopecia
      remained. We propose that these cases represent a type of alopecia caused by a
      combination of pressure ischemia and acute traction alopecia.

PMID- 29656556
TI  - Melt Electrowriting of Thermoplastic Elastomers.
AB  - Melt electrowriting (MEW), an additive manufacturing process, is established
      using polycaprolactone as the benchmark material. In this study, a thermoplastic
      elastomer, namely, poly(urea-siloxane), is synthesized and characterized to
      identify how different classes of polymers are compatible with MEW. This
      polyaddition polymer has reversible hydrogen bonding from the melt upon
      heating/cooling and highly resolved structures are achieved by MEW. The influence
      of applied voltage, temperature, and feeding pressure on printing outcomes
      behavior is optimized. Balancing these parameters, highly uniform and smooth
      surfaced fibers with diameters ranging from 10 to 20 um result. The quality of
      the 3D MEW scaffolds is excellent, with very accurate fiber stacking capacity-up
      to 50 layers with minimal defects and good fiber fusion between the layers. There
      is also minimal fiber sagging between the crossover points, which is a
      characteristic of thicker MEW scaffolds previously reported with other polymers.
      In summary, poly(urea-siloxane) demonstrates outstanding compatibility with the
      MEW process and represents a class of polymer-thermoplastic elastomers-that are,
      until now, untested with this approach.

PMID- 29656557
TI  - Possible interesting link between Janus kinase 2 mutation and renovascular
      hypertension.

PMID- 29656558
TI  - Deep-Ultraviolet Nonlinear Optical Crystal Cs2 Al2 (B3 O6 )2 O: A Benign Member
      of the Sr2 Be2 (BO3 )2 O Family with [Al2 (B3 O6 )2 O]2- Double Layers.
AB  - For the explorations of deep ultraviolet (DUV) nonlinear optical (NLO) borates, a
      type of important optoelectronic material, the (BO3 )3- group has been long
      regarded as the sole microscopic optically-active unit, and toxic Be-containing
      raw materials are frequently-adopted. Herein, a new DUV NLO crystal, Cs2 Al2 (B3
      O6 )2 O (CABO), was designed and synthesized by simultaneously replacing the (BO3
      )3- groups and Be2+ cations for (B3 O6 )3- units and Al3+ cations in Sr2 Be2 (BO3
      )2 O, which possesses a favorable structure, through a chemical co-substitution
      approach. CABO exhibits a considerable DUV NLO capability because of the wide
      band gap and large birefringence originating from the [Al2 (B3 O6 )2 O]2- double
      layers. Remarkably, CABO melts congruently and does not contain the toxic
      beryllium, which is favorable for bulk-size crystal growth and practical
      applications.

PMID- 29656560
TI  - Preoperative criterion identifying a low-risk group for lymph node metastasis in
      intrahepatic cholangiocarcinoma.
AB  - BACKGROUND: Imaging study cannot identify patients with potential low-risk for
      lymph node (LN) metastasis in intrahepatic cholangiocarcinoma (ICC). The purpose
      of this study was to identify a low-risk group for LN metastasis in ICC using
      preoperatively available factors. METHODS: Data from 127 consecutive patients,
      who underwent curative intent surgery for ICC at Kyoto University Hospital and
      Kitano Hospital between 2002 and 2016, were retrospectively analyzed. By using
      only preoperative data, multiple linear regression model for predicting LN
      metastasis was developed. RESULTS: Forty-three patients exhibited LN metastasis
      (33.9%). Serum CA19-9 levels >=37 IU/ml, ICC with hilar invasion, and LN swelling
      were identified as independent preoperative predictors of LN metastasis. The
      prediction model for LN metastasis using these three factors revealed good
      discrimination (area under the receiver operating characteristics curve 0.874, P
      < 0.001). Negative for all three factors (i.e. CA19-9 levels <37 IU/ml,
      peripheral ICC and no LN swelling) identified 35 patients (27.6%) as a low-risk
      group, with the false negative rate of 2.3%. CONCLUSIONS: We proposed a
      preoperative criterion for predicting LN metastasis, giving rise to the
      identification of ICC patients who showed a low-risk of LN metastasis.

PMID- 29656561
TI  - Advances in Controlling Differentiation of Adult Stem Cells for Peripheral Nerve
      Regeneration.
AB  - Adult stems cells, possessing the ability to grow, migrate, proliferate, and
      transdifferentiate into various specific phenotypes, constitute a great asset for
      peripheral nerve regeneration. Adult stem cells' ability to undergo
      transdifferentiation is sensitive to various cell-to-cell interactions and
      external stimuli involving interactions with physical, mechanical, and chemical
      cues within their microenvironment. Various studies have employed different
      techniques for transdifferentiating adult stem cells from distinct sources into
      specific lineages (e.g., glial cells and neurons). These techniques include
      chemical and/or electrical induction as well as cell-to-cell interactions via co
      culture along with the use of various 3D conduit/scaffold designs. Such scaffolds
      consist of unique materials that possess controllable physical/mechanical
      properties mimicking cells' natural extracellular matrix. However, current
      limitations regarding non-scalable transdifferentiation protocols, fate
      commitment of transdifferentiated stem cells, and conduit/scaffold design have
      required new strategies for effective stem cells transdifferentiation and
      implantation. In this progress report, a comprehensive review of recent advances
      in the transdifferentiation of adult stem cells via different approaches along
      with multifunctional conduit/scaffolds designs is presented for peripheral nerve
      regeneration. Potential cellular mechanisms and signaling pathways associated
      with differentiation are also included. The discussion with current challenges in
      the field and an outlook toward future research directions is concluded.

PMID- 29656559
TI  - Shaping eosinophil identity in the tissue contexts of development, homeostasis,
      and disease.
AB  - Eosinophils play homeostatic roles in different tissues and are found in several
      organs at a homeostatic baseline, though their tissue numbers increase
      significantly in development and disease. The morphological, phenotypical, and
      functional plasticity of recruited eosinophils are influenced by the dynamic
      tissue microenvironment changes between homeostatic, morphogenetic, and disease
      states. Activity of the epithelial-mesenchymal interface, extracellular matrix,
      hormonal inputs, metabolic state of the environment, as well as epithelial and
      mesenchymal-derived innate cytokines and growth factors all have the potential to
      regulate the attraction, retention, in situ hematopoiesis, phenotype, and
      function of eosinophils. This review examines the reciprocal relationship between
      eosinophils and such tissue factors, specifically addressing: (1) tissue
      microenvironments associated with the presence and activity of eosinophils; (2)
      non-immune tissue ligands regulatory for eosinophil accumulation, hematopoiesis,
      phenotype, and function (with an emphasis on the extracellular matrix and
      epithelial-mesenchymal interface); (3) the contribution of eosinophils to
      regulating tissue biology; (4) eosinophil phenotypic heterogeneity in different
      tissue microenvironments, classifying eosinophils as progenitors, steady state
      eosinophils, and Type 1 and 2 activated phenotypes. An appreciation of eosinophil
      regulation by non-immune tissue factors is necessary for completing the picture
      of eosinophil immune activation and understanding the functional contribution of
      these cells to development, homeostasis, and disease.

PMID- 29656562
TI  - Aerobic bacteria on cervical cytology.

PMID- 29656563
TI  - Factors affecting publication in peer-reviewed journals of abstracts presented
      from 2008 to 2012 ACVO meetings.
AB  - PURPOSE: To examine variables that affect publication of ACVO meeting abstracts
      in peer-reviewed journals and compare results to ECVO publication rate (PR).
      METHODS: Published papers were identified via online searches for abstracts from
      2008 to 2012 ACVO/ECVO meetings. Variables analyzed (via Pearson's chi-Squared
      test) included the following: oral presentation/poster, type of abstract
      (clinical/basic science/case report), species, ocular tissue, nationality,
      funding, first/last/any author a diplomate, resident as first author, and author
      affiliation (private practice/university). RESULTS: One hundred and eighty-six of
      577 ACVO abstracts were published within 608 +/- 479 days, with 103 published in
      Veterinary Ophthalmology. Significant factors included the following: nationality
      of first/last authors (P = .005); English as first language (P < .001);
      presentation type (P < .001, oral 40% PR, poster 22% PR); type of study (P =
      .037, clinical study 35% PR, basic science 30% PR, case report 16% PR); resident
      as first author (P < .001); diplomate as any author except first/last (P < .001);
      first author affiliation (P = .001, university 37% PR, practice 21% PR); last
      author affiliation (P = .003, university 36% PR, practice 22% PR); and species (P
      < .001, horses 53% PR, multiple species 50% PR, cats 35% PR, food animals 31% PR,
      exotics/wildlife 31% PR, dogs 27% PR, laboratory animals/in vitro 24%).
      Nonsignificant factors were as follows: diplomate as first/last author, funding,
      and ocular tissue. Presentation type, resident as first author, university
      affiliation of first author, and species had the greatest effect on publication
      probability. For the same period, ECVO PR was 87 of 299, which was not
      significantly different from ACVO PR (P = .342). CONCLUSION: At 32%, ACVO PR for
      the study years is similar to ECVO PR of 29%.

PMID- 29656564
TI  - Picophytoplankton size and biomass around equatorial eastern Indian Ocean.
AB  - The cellular size and biomass of picophytoplankton were studied by flow cytometer
      during spring monsoon (March-May of 2015) in equatorial eastern Indian Ocean. We
      established an empirical relationship between forward scatter and cellular size
      to address the size and biomass of picophytoplankton. Results indicated that mean
      cell diameter of Prochlorococcus (0.60 MUm) was the smallest, and then followed
      by Synechococcus (0.98 MUm) and picoeukaryotic phytoplankton (1.05 MUm).
      Thereafter, the biomass converted by abundance reached 0.64 MUg.C.L-1 for
      Prochlorococcus, 0.34 MUg.C.L-1 for Synechococcus, and 0.20 MUg.C.L-1 for
      picoeukaryotic phytoplankton. Additionally, the distinct biomass contribution of
      picophytoplankton appeared to be affected by abundance, but not changes in
      cellular size. Vertically, the cellular sizes of picophytoplankton were
      remarkably small in upper waters, which was predominantly controlled by the
      nutrient availability. In contrast, they were larger in deeper waters, which was
      primarily attributed to the combined effects of low temperature and reduced light
      availability. Spatially, under the influence of high nutrient concentration
      induced by the different circulations and coastal upwelling, slightly high carbon
      biomass of picophytoplankton was observed around the coastal zones of Sri Lanka
      island and Sumatra, as well as the southern Bay of Bengal.

PMID- 29656565
TI  - Rural-Urban Differences in Costs of End-of-Life Care for the Last 6 Months of
      Life Among Patients with Breast, Lung, or Colorectal Cancer.
AB  - PURPOSE: The purpose of this study was to examine rural-urban differences in
      utilization and expenditures in the last 6 months of life for patients with
      breast, lung, or colorectal cancer. METHODS: The study used a 5% sample of the
      2013 Medicare Research Identifiable Files to study utilization and expenditures
      for beneficiaries with breast, lung, or colorectal cancer during the last 6
      months before death (n = 6,214). End of life expenditures were calculated as the
      sum of total Medicare expenditures for inpatient, outpatient, physician, home
      health, hospice, and skilled nursing facility costs during the last 6 months of
      life. FINDINGS: For each type of cancer, total Medicare expenditures in the last
      6 months of life were lower for rural decedents compared to their urban
      counterparts. During the last 6 months of life, median Medicare expenditures were
      lower for rural decedents for breast cancer ($21,839 vs $25,698), lung cancer
      ($22,814 vs $27,635), and colorectal cancer ($24,156 vs $28,035; all differences
      significant at P < .05). In adjusted models, care for rural decedents was less
      costly than urban decedents for breast, lung, and colorectal cancer,
      respectively. CONCLUSIONS: Our findings indicate that Medicare expenditures are
      lower for rural beneficiaries with each type of cancer than urban beneficiaries,
      even after adjusting for age, gender, race, dual eligibility, region, chronic
      conditions, and type of service utilization. The findings from this study can be
      useful for policymakers in developing programs and resource allocation decisions
      that impact rural beneficiaries.

PMID- 29656566
TI  - Absence of human skin irritation and allergenic potential after repeated patch
      applications of a lamellar moisturizer.
AB  - BACKGROUND: New cosmetic products should undergo clinical evaluation for skin
      sensitization potential. OBJECTIVES: To assess the irritation and sensitization
      potential of a moisturizer containing lamellar structured lipids after repeated
      patch application in humans, using human repeated insult patch test methodology.
      METHODS: This 6-week, single-center, open-label study compared a lamellar
      moisturizer with negative saline control in human subjects aged 18-70 years and
      skin phototype (Fitzpatrick) classification I-IV. During an initial induction
      phase, semi-occlusive multi-test patches were applied to the skin of
      participants' backs three times per week for 3 consecutive weeks; clinical
      assessments were performed per International Contact Dermatitis Research Group
      criteria. Participants subsequently underwent a challenge phase, where a new
      patch was applied to a contact-naive area of the skin to assess sensitization to
      the moisturizer. RESULTS: The study commenced with 233 voluntary participants,
      214 of whom completed the study and underwent the final dermatological
      assessment. Most participants (232/233; 99.6%) demonstrated negative patch test
      results. One participant had a positive reaction at the lamellar moisturizer
      application site, with visible erythema and edema (classified as an adverse event
      [AE]); however, this reaction was observed 24 hours after a reaction to another
      product in the patch test panel (a prototype cleanser). Importantly, no skin
      reactions were detected during the challenge phase. Two participants had AEs of
      mild contact dermatitis in the area of patch adhesive application during the
      induction phase. No serious AEs occurred during the study. CONCLUSIONS: These
      findings suggest that the lamellar moisturizer has low irritant and allergenic
      potential.

PMID- 29656567
TI  - Major venom proteins of the fire ant Solenopsis invicta: insights into possible
      pheromone-binding function from mass spectrometric analysis.
AB  - Proteins in the venom of the fire ant Solenopsis invicta have been suggested to
      function in pheromone binding. Venom from queens and workers contains different
      isoforms of these proteins, consistent with the differing pheromones they
      secrete, but questions remain about the venom protein composition and glandular
      source. We found that the queen venom contains a previously uncharacterized
      pheromone-binding protein paralogue known as Sol i 2X1. Using imaging mass
      spectrometry, we located the main venom proteins in the poison sac, implying that
      pheromones might have to compete with venom alkaloids for binding. Using the
      known structure of the worker venom protein Sol i 2w, we generated three
      dimensional homology models of the worker venom protein Sol i 4.02, and of the
      two main venom proteins in queens and female alates, Sol i 2q and Sol i 2X1.
      Surprisingly, the models show that the proteins have relatively small internal
      hydrophobic binding pockets that are blocked by about 10 amino acids of the C
      terminal region. For these proteins to function as carriers of hydrophobic
      ligands, a conformational change would be required to displace the C-terminal
      region, somewhat like the mechanism known to occur in the silk moth pheromone
      binding protein.

PMID- 29656568
TI  - Nanofiber-Based Hydrogels: Controllable Synthesis and Multifunctional
      Applications.
AB  - Nanofiber-based hydrogels (NFHGs) prepared by the combination of traditional
      hydrogels and novel nanofibers have demonstrated great potential in various
      application fields, owing to their integrated advantages of superhydrophilicity,
      high water-holding capacity, good biocompatibility, enhanced mechanical strength,
      and excellent structural tenability. In this review, a comprehensive overview of
      the structure design and synthetic strategy of NFHGs derived from electrospinning
      technique, weaving, freeze-drying, 3D printing, and molecular self-assembling
      method is provided. The widely researched multifunctional applications, primarily
      involving tissue engineering, drug delivery, sensing, intelligent actuator, and
      oil/water separation are also presented. Furthermore, some unsolved scientific
      issues and possible directions for future development of this field are also
      intensively discussed.

PMID- 29656570
TI  - Predatory journals and their effect on the advancement of nursing science.

PMID- 29656569
TI  - Ghanaian parents' perceptions of pre and postnatal nutrient supplements and their
      effects.
AB  - Small-quantity lipid-based nutrient supplements (SQ-LNS) have been studied in
      efficacy and effectiveness trials, but little is known about how parents perceive
      the products and their effects. In a randomised trial in Ghana, efficacy of SQ
      LNS provided to women during pregnancy and the first 6 months postpartum and to
      their children from 6 to 18 months of age was assessed by comparison with iron
      folic acid (IFA) capsules and multiple micronutrient (MMN) capsules provided to
      women. In a follow-up study conducted when the index children from the original
      trial were between 4 and 6 years of age, we used survey-based methods to assess
      retrospective and current parental perceptions of nutrient supplements generally
      and of SQ-LNS and their effects compared with perceptions IFA and MMN capsules.
      Most parents perceived that the assigned supplements (SQ-LNS, IFA, or MMN)
      positively impacted the mother during pregnancy (approximately 89% of both
      mothers and fathers) and during lactation (84% of mothers and 86% of fathers).
      Almost all (>=90%) of mothers and fathers perceived that the assigned supplement
      positively impacted the index child and expected continued positive impacts on
      the child's health and human capital into the future. A smaller percentage of
      parents perceived negative impacts of the supplements (7%-17% of mothers and 4%
      12% of fathers). Perceptions of positive impacts and of negative impacts did not
      differ by intervention group. The results suggest that similar populations would
      likely be receptive to programs to deliver SQ-LNS or micronutrient capsules.

PMID- 29656571
TI  - Daily Snacking Occasions and Weight Status Among US Children Aged 1 to 5 Years.
AB  - OBJECTIVE: To characterize associations of snacking frequency with weight status
      among US children aged 1 to 5 years. METHODS: Participants were children (n =
      4,669) aged 1 to 5 years in the 2005 to 2014 National Health and Nutrition
      Examination Survey (NHANES). Snacking was assessed by two 24-hour dietary recalls
      using definitions that considered "snack" occasions as well as other
      foods/beverages consumed between meals. Overweight/obesity (OW/OB) was defined
      using percentile cutoffs: >= 97.7th weight-for-length (< 2 years) cutoff and the
      >= 85th BMI-for-age (>= 2 years) cutoff. Linear/logistic regressions evaluated
      snacking based on daily occasions and relative to current recommendations (two to
      three snacks per day). RESULTS: During 2005 to 2014, US children aged 1 to 5
      years consumed, on average, two to three snacks daily. Children with normal
      weight in both age groups tended to snack less frequently than children with
      OW/OB when considering all foods/beverages eaten between meals (P < 0.01-0.12).
      Across most snacking definitions, children < 2 years who snacked more frequently
      than recommended had greater odds of having OW/OB (P < 0.01-0.12) and consumed
      greater daily snack energy than those who snacked within recommendations (all P <
      0.01). Recommendations did not clearly delineate weight status among children
      aged 2 to 5 years. CONCLUSIONS: Snacking frequency and weight are positively
      associated among US children 1 to 5 years old, with most consistent associations
      seen among children < 2 years old and when considering all foods/beverages
      consumed between meals.

PMID- 29656572
TI  - Binding of Lanthanide Complexes to Histidine-Containing Peptides Probed by Raman
      Optical Activity Spectroscopy.
AB  - Lanthanide complexes are used as convenient spectroscopic probes for many
      biomolecules. Their binding to proteins is believed to be enhanced by the
      presence of histidine, but the strength of the interaction significantly varies
      across different systems. To understand the role of peptide length and sequence,
      short histidine-containing peptides have been synthesized (His-Gly, His-Gly-Gly,
      His-Gly-Gly-Gly, Gly-His, Gly-His-Gly, His-His, and Gly-Gly-His) and circularly
      polarized luminescence (CPL) induced at the [Eu(dpa)3 ]3- complex has been
      measured by means of a Raman optical activity (ROA) spectrometer. The obtained
      data indicate relatively weak binding of the histidine residue to the complex,
      with a strong participation of other parts of the peptide. Longer peptides, low
      pH, and a histidine residue close to the N-peptide terminus favor the binding.
      The binding strengths are approximately proportional to the CPL intensity and
      roughly correlate with predictions based on molecular dynamics (MD) simulations.
      The specificity of lanthanide binding to the peptide structure and its intense
      luminescence and high optical activity make the ROA/CPL technique suitable for
      probing secondary and tertiary structures of peptides and proteins.

PMID- 29656573
TI  - Heart-brain interactions in patients with heart failure, including takotsubo
      syndrome: a need to monitor autonomic sympathetic activity: reply.

PMID- 29656574
TI  - NMReDATA, a standard to report the NMR assignment and parameters of organic
      compounds.
AB  - Even though NMR has found countless applications in the field of small molecule
      characterization, there is no standard file format available for the NMR data
      relevant to structure characterization of small molecules. A new format is
      therefore introduced to associate the NMR parameters extracted from 1D and 2D
      spectra of organic compounds to the proposed chemical structure. These NMR
      parameters, which we shall call NMReDATA (for nuclear magnetic resonance
      extracted data), include chemical shift values, signal integrals, intensities,
      multiplicities, scalar coupling constants, lists of 2D correlations, relaxation
      times, and diffusion rates. The file format is an extension of the existing
      Structure Data Format, which is compatible with the commonly used MOL format. The
      association of an NMReDATA file with the raw and spectral data from which it
      originates constitutes an NMR record. This format is easily readable by humans
      and computers and provides a simple and efficient way for disseminating results
      of structural chemistry investigations, allowing automatic verification of
      published results, and for assisting the constitution of highly needed open
      source structural databases.

PMID- 29656575
TI  - Experimental and clinical antihypertensive activity of Matricaria chamomilla
      extracts and their angiotensin-converting enzyme inhibitory activity.
AB  - Three different extracts of Matricaria chamomilla L. were evaluated for their
      antihypertensive activity, these extracts were total alcohol extract (Extract 1),
      oil extracted (Extract 2), and water lifted after oil extraction (Extract 3).
      Quantitative and Qualitative analyses were carried out for all extracts. The 3
      extracts were proved to be safe for human use. A single oral administration of
      the plant extracts (200 mg/kg) decreases both systolic and diastolic blood
      pressure of normotensive rats after 1, 1.5, and 2 hr. Furthermore, groups treated
      with the evaluated extracts (100 & 200 mg/kg) or Captopril (20 mg/kg) showed a
      significant reduction in the elevated blood pressure and heart rate. Extract 3
      showed the most antihypertensive activity. Serum biochemical parameters and lipid
      profile levels of treated groups were improved in comparison with induced
      hypertensive untreated rats. In evaluation of oxidative damage parameters
      Glutathione and superoxide dismutase (SOD) in some organs, the investigated
      extracts or captopril restored the amount of reduced Glutathione in tissues in
      addition to an increase in the activity of the SOD after a significant depletion
      of SOD activity. In the clinical study, there was a significant dose dependent
      decrease in Systolic blood pressure, Diastolic blood pressure, and heart rate
      compared with their basal values in both normotensive and hypertensive human
      volunteers after oral administration of Matricaria chamomilla beverages.

PMID- 29656576
TI  - Repurposing carbamazepine for the treatment of amyotrophic lateral sclerosis in
      SOD1-G93A mouse model.
AB  - AIMS: To investigate the effect and mechanisms of carbamazepine (CBZ) on the
      onset and progression of amyotrophic lateral sclerosis (ALS) in SOD1-G93A mouse
      model. METHODS: Starting from 64 days of age, SOD1-G93A mice were orally
      administered with CBZ at 200 mg/kg once daily until death. The disease onset and
      life span of SOD1-G93A mice were recorded. Motor neurons (MNs) in anterior horn
      of spinal cord were quantified by Nissl staining and SMI-32 immunostaining.
      Hematoxylin and eosin (H&E), nicotinamide adenine dinucleotide hydrogen (NADH),
      modified Gomori trichrome (MGT), and alpha-bungarotoxin-ATTO-488 staining were
      also performed to evaluate muscle and neuromuscular junction (NMJ) damage.
      Expressions of aggregated SOD1 protein and autophagy-related proteins were
      further detected by Western blot and immunofluorescent staining. RESULTS:
      Carbamazepine treatment could delay the disease onset and extend life span of
      SOD1-G93A mice by about 14.5% and 13.9%, respectively. Furthermore, CBZ treatment
      reduced MNs loss by about 46.6% and ameliorated the altered muscle morphology and
      NMJ. Much more interestingly, mechanism study revealed that CBZ treatment
      activated autophagy via AMPK-ULK1 pathway and promoted the clearance of mutant
      SOD1 aggregation. CONCLUSION: Our findings uncovered the therapeutic effects of
      CBZ against disease pathogenesis in SOD1-G93A mice, indicating a promising
      clinical utilization of CBZ in ALS therapy.

PMID- 29656578
TI  - Long-term single-center comparison of ICD lead survival: Evidence for premature
      Linox lead failure.
AB  - INTRODUCTION: ICD lead failure is a potential source of significant morbidity and
      mortality. This study investigates the survival rates of Sprint Quattro, Endotak
      Reliance, and Linox ICD leads. METHODS AND RESULTS: A retrospective cohort study
      of all patients with an ICD implanted between January 2007 and December 2012 from
      the Wellington Hospital region, New Zealand, a tertiary referral center. Lead and
      patient details were established by review of clinical notes and the PaceArt
      Optima database. We analyzed a total of 287 implants using Sprint Quattro (n  = 
      92), Endotak Reliance (n  =  37), Linox (n  =  151), Riata (n  =  4), and Sprint
      Fidelis (n  =  2) leads. Median follow-up was 61.6 (26.0-81.6) months for Sprint
      Quattro leads, 66.7 (53.3-88.8) months for Linox leads, and 82.9 (45.9-107.4)
      months for Endotak Reliance leads. There were 20 cases of lead failure of which
      19 were in Linox leads. The 4-, 6-, and 8-year survival for Linox leads was 97%
      (92.6-99.1), 93% (85.5-96.5), and 76% (62.3-85.5), respectively. The predominant
      abnormality was detection of nonphysiological electrical signals. Linox lead
      failure was associated with a younger age of patient (49.2 vs. 57.7 years, P  = 
      0.007). CONCLUSIONS: The 7-year survival of Linox leads was significantly worse
      than shown in Biotronik surveillance reports, but in line with other single
      center studies from around the world.

PMID- 29656577
TI  - Efficacy of 7-benzyloxyindole and other halogenated indoles to inhibit Candida
      albicans biofilm and hyphal formation.
AB  - Certain pathogenic bacteria and yeast form biofilms on biotic and abiotic
      surfaces including medical devices and implants. Hence, the development of
      antibiofilm coating materials becomes relevant. The virulence of those colonizing
      pathogens can be reduced by inhibiting biofilm formation rather than killing
      pathogens using excessive amounts of antimicrobials, which is touted as one of
      the main reasons for the development of drug resistance. Candida albicans is an
      opportunistic fungal pathogen, and the transition of yeast cells to hyphal cells
      is believed to be a crucial virulence factor. Previous studies have shown that
      indole and its derivatives possess antivirulence properties against various
      bacterial pathogens. In this study, we used various indole derivatives to
      investigate biofilm-inhibiting activity against C. albicans. Our study revealed
      that 7-benzyloxyindole, 4-fluoroindole and 5-iodoindole effectively inhibited
      biofilm formation compared to the antifungal agent fluconazole. Particularly, 7
      benzyloxyindole at 0.02 mM (4.5 MUg ml-1 ) significantly reduced C. albicans
      biofilm formation, but had no effect on planktonic cells, and this finding was
      confirmed by a 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5
      carboxanilide (XTT) assay and three-dimensional confocal laser scanning
      microscopy. Scanning electron microscopy analyses revealed that 7-benzyloxyindole
      effectively inhibited hyphal formation, which explains biofilm inhibition.
      Transcriptomic analysis showed that 7-benzyloxyindole downregulated the
      expressions of several hypha/biofilm-related genes (ALS3, ECE1, HWP1 and RBT1). A
      C. albicans-infected Caenorhabditis elegans model system was used to confirm the
      antivirulence efficacy of 7-benzyloxyindole.

PMID- 29656579
TI  - Turkish adaptation and psychometric characteristics of the Nursing Authority and
      Autonomy Scale.
AB  - AIM: To adapt the Nursing Authority and Autonomy Scale (NAAS) into Turkish the
      Nursing Authority and Autonomy Scale (NAAS) to Turkish and assess its
      psychometric properties for Turkish nurses and nurse managers. BACKGROUND: The
      NAAS is a tool that specifically measures nursing authority and autonomy from the
      perspectives of nurses and nurse managers. METHODS: The study sample consisted of
      160 nurse managers and 266 staff nurses. Content validity was assessed using
      expert approval. Construct validity was assessed using confirmatory factor
      analysis. Internal consistency was assessed using Cronbach's alpha, and the test
      retest reliability was assessed using Pearson's correlation coefficients.
      RESULTS: The model achieved a good fit. The internal reliability of the NAAS'
      authority and autonomy in nursing practice and importance of nursing practice
      subscales were .84. The Cronbach's alpha of the instrument was .88. The test
      retest scores within an interval of 3 weeks were statistically not significant.
      CONCLUSIONS: The Turkish version of the NAAS has good psychometric properties and
      this scale can be employed to measure nurses' authority and autonomy. IMPLICATION
      FOR NURSING MANAGEMENT: Nurse managers and educators should use an appropriate
      scale such as NAAS in order to assess nurses' clinical authority and autonomy to
      improve patient outcomes and develop nurses.

PMID- 29656580
TI  - Declining home range area predicts reduced late-life survival in two wild
      ungulate populations.
AB  - Demographic senescence is increasingly recognised as an important force shaping
      the dynamics of wild vertebrate populations. However, our understanding of the
      processes that underpin these declines in survival and fertility in old age
      remains limited. Evidence for age-related changes in foraging behaviour and
      habitat use is emerging from wild vertebrate studies, but the extent to which
      these are driven by within-individual changes, and the consequences for fitness,
      remain unclear. Using longitudinal census observations collected over four
      decades from two long-term individual-based studies of unmanaged ungulates, we
      demonstrate consistent within-individual declines in home range area with age in
      adult females. In both systems, we found that within-individual decreases in home
      range area were associated with increased risk of mortality the following year.
      Our results provide the first evidence from the wild that age-related changes in
      space use are predictive of adult mortality.

PMID- 29656581
TI  - Japan NBI Expert Team classification: Narrow-band imaging magnifying endoscopic
      classification of colorectal tumors.

PMID- 29656582
TI  - Hyperactive cyclic motor activity in the distal colon after colonic surgery as
      defined by high-resolution colonic manometry.
AB  - BACKGROUND: Recovery after colonic surgery is invariably delayed by disturbed gut
      motility. It is commonly assumed that colonic motility becomes quiescent after
      surgery, but this hypothesis has not been evaluated rigorously. This study
      quantified colonic motility through the early postoperative period using high
      resolution colonic manometry. METHODS: Fibre-optic colonic manometry was
      performed continuously before, during and after surgery in the left colon and
      rectum of patients undergoing right hemicolectomy, and in healthy controls. Motor
      events were characterized by pattern, frequency, direction, velocity, amplitude
      and distance propagated. RESULTS: Eight patients undergoing hemicolectomy and
      nine healthy controls were included in the study. Colonic motility became
      markedly hyperactive in all operated patients, consistently dominated by cyclic
      motor patterns. Onset of cyclic motor patterns began to a minor extent before
      operation, occurring with increasing intensity nearer the time of surgery; the
      mean(s.d.) active duration was 12(7) per cent over 3 h before operation and
      43(17) per cent within 1 h before surgery (P = 0.024); in fasted controls it was
      2(4) per cent (P < 0.001). After surgery, cyclic motor patterns increased
      markedly in extent and intensity, becoming nearly continuous (active duration
      94(13) per cent; P < 0.001), with peak frequency 2-4 cycles per min in the
      sigmoid colon. This postoperative cyclic pattern was substantially more prominent
      than in non-operative controls, including in the fed state (active duration
      27(20) per cent; P < 0.001), and also showed higher antegrade velocity (P <
      0.001). CONCLUSION: Distal gut motility becomes markedly hyperactive with colonic
      surgery, dominated by cyclic motor patterns. This hyperactivity likely represents
      a novel pathophysiological aspect of the surgical stress response. Hyperactive
      motility may contribute to gut dysfunction after surgery, potentially offering a
      new therapeutic target to enhance recovery.

PMID- 29656583
TI  - Chiral Atropisomeric Indenocorannulene Bowls: Critique of the Cahn-Ingold-Prelog
      Conception of Molecular Chirality.
AB  - Chiral corannulenes abound, but suffer generally from configurational lability
      associated with bowl-to-bowl inversion, thus obviating questions of
      stereogenicity and stereoelement construction. In contrast, peri-annulated
      corannulenes show greatly increased barriers for bowl-to-bowl inversion;
      specifically indenocorannulenes invert on a time scale too slow to observe by
      normal NMR methods and raise the possibility of creating chiral atropisomeric
      bowl-shaped aromatics. Two methods for preparing indenocorannulene from simple 2
      haloarylcorannulenes-silyl cation C-F activation, and Pd-mediated C-Cl
      activation[5] -enable the synthesis of an array of such chiral atropisomeric
      indenocorannulenes. Resolution of the enantiomers by high-performance liquid
      chromatography over chiral support phases motivates the study of chiroptical
      properties, the assignment of absolute "Cartesian" configuration, and the
      assessment of configurational stability. These studies bring into question any
      systematic assignment of nontrivial stereoelements (i.e. not the molecule in its
      entirety) and refute any assertion of congruence between "Cahn-Ingold-Prelog
      elements" and the physical or "Cartesian" basis of chirality.

PMID- 29656584
TI  - Improving lymph node characterization in staging malignant lymphoma using first
      order ADC texture analysis from whole-body diffusion-weighted MRI.
AB  - BACKGROUND: Correct staging and treatment initiation in malignant lymphoma
      depends on accurate lymph node characterization. However, nodal assessment based
      on conventional and diffusion-weighted (DWI) MRI remains challenging,
      particularly in smaller nodes. PURPOSE: To evaluate first-order apparent
      diffusion coefficient (ADC) texture parameters compared to mean ADC for lymph
      node characterization in non-Hodgkin lymphoma (NHL) using whole-body DWI (WB
      DWI). STUDY TYPE: Retrospective. POPULATION: Twenty-eight patients with NHL.
      FIELD STRENGTH/SEQUENCE: 3T whole-body DWI using two b-values (0-1000 s/mm2 ).
      ASSESSMENT: Regions of interest were drawn on the three most hyperintense lymph
      nodes on b1000-images, irrespective of size, in all nodal body regions.
      Diagnostic performance of mean ADC (ADCmean ) was compared with first-order ADC
      texture parameters: standard deviation (ADCstdev ), kurtosis (ADCkurt ), and
      skewness (ADCskew ). Additional subanalyses focused on the accuracy of ADCmean
      and ADC texture parameters in different lymph node volumes and nodal regions.
      STATISTICAL TESTS: Benign and malignant nodes were compared using Mann-Whitney U
      tests with 18-Fluoro-deoxyglucose positron emission tomography computed
      tomography and bone marrow biopsy as reference standard. Receiver operating
      characteristic analyses were performed to determine cutoff values and calculate
      sensitivity, specificity, accuracy, and positive and negative predictive value
      (PPV, NPV). RESULTS: ADCmean (P = 0.008), ADCskew and ADCkurt differed
      significantly between benign and malignant nodes (P < 0.001), while ADCstdev
      didn't (P = 0.21). ADCskew was the best discriminating parameter, with 79%
      sensitivity, 86% specificity, 83% accuracy, 85% PPV, and 81% NPV. In every volume
      category, ADCskew yielded the highest accuracy (88% in 0-25th percentile volume,
      75% in 25th -75th percentile, 93% in 75-100th percentile). On a per-region basis,
      ADCskew accuracy varied 13.6% between nodal regions, while ADCmean , ADCkurt ,
      and ADCstdev showed interregional variation of 17.4%, 20.3%, and 14.9%,
      respectively. DATA CONCLUSION: First-order ADC texture analysis with WB-DWI
      improved lymph node characterization compared to ADCmean . ADCskew was the most
      accurate and robust discriminatory parameter over all lymph node volumes and
      nodal body regions. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn.
      Reson. Imaging 2018;48:897-906.

PMID- 29656585
TI  - Adenocarcinoma in situ admixed with small cell neuroendocrine carcinoma of the
      cervix: A case report with cytological features.
AB  - Primary cervical small cell neuroendocrine carcinoma (SCNEC) is a rare and
      aggressive tumor. Herein, we describe the first cytological case of
      adenocarcinoma in situ (AIS) admixed with SCNEC. A 65-year-old postmenopausal
      Japanese female presented with abnormal genital bleeding. The Papanicolaou smear
      of the cervix demonstrated the presence of 2 distinct neoplastic components in an
      inflammatory background. One component consisted of aggregates of small round
      cells with a high nuclear/cytoplasmic ratio and round to oval nuclei with powdery
      chromatin, and inconspicuous nucleoli. Nuclear molding was characteristic. The
      other component consisted of irregular overlapping clusters of tall columnar
      cells with large round to oval nuclei containing coarse chromatin, and relatively
      rich cytoplasm. Accordingly, AIS admixed with SCNEC was suspected. Although the
      cytological features of cervical SCNEC are characteristic, the cytodiagnosis of
      this type of tumor may be difficult because of the rarity of the tumor. The
      presence of non-neuroendocrine tumor components in cervical SCNEC is not unusual,
      therefore careful observation is needed not to miss SCNEC components in the
      diagnosis of squamous cell carcinoma and/or adenocarcinoma in cervical
      cytological specimens.

PMID- 29656586
TI  - Prospective assessment of the predictive value of the BRCA1 gene status in
      sarcoma patients treated with trabectedin: an updated analysis of the EORTC 62091
      trial.
AB  - We describe the predictive value of BRCA1 gene status on trabectedin efficacy and
      found no correlation despite the mechanisms of action of this drug that rely on
      DNA repair systems.

PMID- 29656587
TI  - Juvenile hormone mediates the positive effects of nitrogen fertilization on
      weight and reproduction in pea aphid.
AB  - BACKGROUND: The positive effects of nitrogen fertilization on the performance of
      phytophagous insects have been reported extensively; the physiological and
      molecular basis involved, however, is largely unclear. Here, we test
      experimentally whether enhancement of juvenile hormone (JH) is responsible for
      the increased weight and fecundity of pea aphid (Acyrthosiphon pisum) under
      nitrogen fertilization. RESULTS: Aphids fed on Medicago truncatula with nitrogen
      fertilization have a greater amino acid content, higher weight at the fourth
      instar and adult stage, and produce more offspring than those without nitrogen
      fertilization. Furthermore, nitrogen fertilization upregulates the transcripts of
      JH biosynthesis-related genes and increases JH titre at the fourth instar and
      adult stage, suggesting that JH is involved in the positive responses of aphids
      to nitrogen fertilization. Application of 100 ng JH increases adult weight and
      fecundity in aphids fed on M. truncatula without nitrogen fertilization.
      Conversely, impairing JH signalling by pharmacologically inhibiting the target of
      rapamycin pathway or by knocking down JH biosynthetic gene decreases adult weight
      and fecundity in aphids fed on M. truncatula with nitrogen fertilization, whereas
      application of JH rescued the phenotype. CONCLUSION: The increased JH titre at
      the fourth instar and adult stage is required for the increases of weight and
      fecundity of A. pisum under nitrogen fertilization. (c) 2018 Society of Chemical
      Industry.

PMID- 29656588
TI  - The use of funnel plots with regression as a tool to visually compare HIV
      treatment outcomes between centres adjusting for patient characteristics and
      size: a UK Collaborative HIV Cohort study.
AB  - OBJECTIVES: A measure used for assessing the effectiveness of HIV care and
      comparing clinical centres is the proportion of people starting antiretroviral
      therapy (ART) with viral suppression (VS) after 1 year. We propose a method that
      adjusts for patients' demographic characteristics, and visually compares this
      measure between different sites accounting for centre size. METHODS: We analysed
      viral load measurements for UK Collaborative HIV Cohort (UK CHIC) patients
      starting ART between 2006 and 2013. We used logistic regression to estimate the
      proportion with VS after 1 year of ART adjusted for patient mix (in terms of age
      and a combined gender/ethnicity/acquisition mode variable) and calendar year. We
      compared outcomes between centres using funnel plots which account for centre
      size. RESULTS: The overall proportion of the cohort with VS 1 year after starting
      ART was 90% and increased from 83% to 93% between 2006 and 2013. VS was lower in
      younger individuals. White men who have sex with men (MSM) had the highest (94%),
      and black African (81%) and white (82%) heterosexual women the lowest proportions
      achieving VS. Comparing the unadjusted funnel plot with the adjusted, there were
      movements of some centres from outside to inside the 95% contour limits, which
      was largely explained by the patient mix of these centres. CONCLUSIONS: VS 1 year
      after ART start was associated with demographic characteristics and centre size;
      therefore, to compare the performances of centres, adjustment for these factors
      is required. Adjusted funnel plot is an effective tool which accounts for both
      the demographic characteristics and the centre size. Social factors, rather than
      treatment decisions within the control of the centres, may drive differences in
      outcomes.

PMID- 29656589
TI  - Creating a Low-Potential Redox Polymer for Efficient Electroenzymatic CO2
      Reduction.
AB  - Increasing greenhouse gas emissions have resulted in greater motivation to find
      novel carbon dioxide (CO2 ) reduction technologies, where the reduction of CO2 to
      valuable chemical commodities is desirable. Molybdenum-dependent formate
      dehydrogenase (Mo-FDH) from Escherichia coli is a metalloenzyme that is able to
      interconvert formate and CO2 . We describe a low-potential redox polymer,
      synthesized by a facile method, that contains cobaltocene (grafted to
      poly(allylamine), Cc-PAA) to simultaneously mediate electrons to Mo-FDH and
      immobilize Mo-FDH at the surface of a carbon electrode. The resulting
      bioelectrode reduces CO2 to formate with a high Faradaic efficiency of 99+/-5 %
      at a mild applied potential of -0.66 V vs. SHE.

PMID- 29656590
TI  - "Got rats?" Global environmental costs of thirst for milk include acute
      biodiversity impacts linked to dairy feed production.
AB  - Rodents damaging alfalfa crops typically destined for export to booming Eastern
      markets often cause economical losses to farmers, but management interventions
      attempting to control rodents (i.e., use of rodenticides) are themselves damaging
      to biodiversity. These damages resonate beyond dairy feed producing regions
      through animal migration and are an overlooked part of the transferred
      environmental burden caused by a growing thirst for milk in China and elsewhere.

PMID- 29656591
TI  - AMP-activated protein kinase-dependent induction of autophagy by erythropoietin
      protects against spinal cord injury in rats.
AB  - AIMS: Autophagy has been regarded as a promising therapeutic target for spinal
      cord injury (SCI). Erythropoietin (EPO) has been demonstrated to exhibit
      neuroprotective effects in the central nervous system (CNS); however, the
      molecular mechanisms of its protection against SCI remain unknown. This study
      aims to investigate whether the neuroprotective effects of EPO on SCI are
      mediated by autophagy via AMP-activated protein kinase (AMPK) signaling pathways.
      METHODS: Functional assessment and Nissl staining were used to investigate the
      effects of EPO on SCI. Expressions of proteins were detected by Western blot and
      immunohistochemistry. RESULTS: Treatment with EPO significantly reduced the loss
      of motor neurons and improved the functional recovery following SCI.
      Erythropoietin significantly enhanced the SCI-induced autophagy through
      activating AMPK and inactivating mTOR signaling. The inhibitor of AMPK, compound
      C, could block the EPO-induced autophagy and beneficial action on SCI, whereas
      the activator of AMPK, metformin, could mimic the effects of EPO. In the in vitro
      studies, EPO enhanced the hypoxia-induced autophagy in an AMPK-dependent manner.
      CONCLUSIONS: The AMPK-dependent induction of autophagy contributes to the
      neuroprotection of EPO on SCI.

PMID- 29656592
TI  - The applicability of furfuryl-gelatin as a novel bioink for tissue engineering
      applications.
AB  - Three-dimensional bioprinting is an innovative technique in tissue engineering,
      to create layer-by-layer structures, required for mimicking body tissues.
      However, synthetic bioinks do not generally possess high printability and
      biocompatibility at the same time. So, there is an urgent need for naturally
      derived bioinks that can exhibit such optimized properties. We used furfuryl
      gelatin as a novel, visible-light crosslinkable bioink for fabricating cell-laden
      structures with high viability. Hyaluronic acid was added as a viscosity enhancer
      and either Rose Bengal or Riboflavin was used as a visible-light crosslinker.
      Crosslinking was done by exposing the printed structure for 2.5 min to visible
      light and confirmed using Fourier transform infrared spectroscopy and rheometry.
      Scanning electron microscopy revealed a highly porous networked structure. Three
      different cell types were successfully bioprinted within these constructs. Mouse
      mesenchymal stem cells printed within monolayer and bilayer sheets showed
      viability, network formation and proliferation (~5.33 times) within 72 h of
      culture. C2C12 and STO cells were used to print a double layered structure, which
      showed evidence of the viability of both cells and heterocellular clusters within
      the construct. This furfuryl-gelatin based bioink can be used for tissue
      engineering of complex tissues and help in understanding how cellular crosstalk
      happens in vivo during normal or diseased pathology. (c) 2018 Wiley Periodicals,
      Inc. J Biomed Mater Res Part B: Appl Biomater, 2018.

PMID- 29656593
TI  - Review article: Investigations and the pregnant woman in the emergency department
      - part 1: Laboratory investigations.
AB  - Accurate assessment of the pregnant patient in the ED depends on knowledge of
      physiological changes in pregnancy, and how these changes may impact on pathology
      tests, appearance on point-of-care ultrasound and electrocardiography. In
      addition the emergency physician needs to be cognisant of disorders that are
      unique to or more common in pregnancy. Part 1 of this review addresses potential
      deviations in laboratory investigation reference intervals resulting from
      physiological alterations in pregnancy, and the important causes of abnormal
      laboratory results in pregnancy. Part 2 will address the role of point-of-care
      ultrasound in pregnancy, physiological changes that may affect interpretation of
      point-of-care ultrasound, physiological changes in electrocardiography, and the
      safety of radiological procedures in the pregnant patient.

PMID- 29656594
TI  - Immune imbalance of global gene expression, and cytokine, chemokine and selectin
      levels in the brains of offspring with social deficits via maternal immune
      activation.
AB  - The murine maternal immune activation (MIA) offspring model enables longitudinal
      studies to explore aberrant social behaviors similar to those observed in humans.
      High levels of cytokines, chemokines and cell adhesion molecules (CAM) have been
      found in the plasma and/or brains of psychiatric patients. We hypothesized that
      upregulation of the systemic or brain immune response has an augmenting effect by
      potentially increasing the interplay between the neuronal and immune systems
      during the growth of the MIA offspring. In this study, a C57BL/6j MIA female
      offspring model exhibiting social deficits was established. The expression of
      fetal interferon (IFN)-stimulated (gbp3, irgm1, ifi44), adolescent
      immunodevelopmental transcription factor (eg, r2, tfap2b), hormone (pomc, hcrt),
      adult selectin (sell, selp) and neuroligin (nlgn2) genes was altered. Systemic
      upregulation of endogenous IL-10 occurred at the adult stage, while both IL-1beta
      and IL-6 were increased and persisted in the sera throughout the growth of the
      MIA offspring. The cerebral IL-6 levels were endogenously upregulated, but both
      MCP-1 (macrophage inflammatory protein-1) and L-selectin levels were
      downregulated at the adolescent and/or adult stages. However, the MIA offspring
      were susceptible to lipopolysaccharide (LPS) stimulation. After reinjecting the
      MIA offspring with LPS in adulthood, a variety of sera and cerebral cytokines,
      chemokines and CAMs were increased. Particularly, both MCP-1 and L-selectin
      showed relatively high expression in the brain compared with the expression
      levels in phosphate-buffered saline (PBS)-treated offspring injected with LPS.
      Potentially, MCP-1 was attracted to the L-selectin-mediated immune cells due to
      augmentation of the immune response following stimulation in MIA female
      offspring.

PMID- 29656595
TI  - Pathways of Association from Stress to Obesity in Early Childhood.
AB  - OBJECTIVE: The objective of this study is to critically review the literature on
      early life stress in relation to obesity in humans, including the multiple
      biological and behavioral mechanisms through which early life stress exposure
      (birth to the age of 5 years) may associate with obesity risk during childhood.
      METHODS: A review of the literature was conducted to identify studies on
      associations between early childhood stress and risk for obesity and the
      mechanisms of association. Multiple databases (PubMed, PsycInfo, Google Scholar)
      were used in the search as well as a "snowball" search strategy. All study
      designs were included. RESULTS: Early life stress and adverse childhood
      experiences are associated with obesity and overweight in adults. Evidence is
      less consistent in children. Studies vary in the nature of the stress examined
      (e.g., chronic vs. acute), sample characteristics, and study designs.
      Longitudinal studies are needed, as the effects of early life stress exposure may
      not emerge until later in the life-span. Early life stress exposure is associated
      with biological and behavioral pathways that may increase risk for childhood
      obesity. CONCLUSIONS: There is evidence that early life stress is associated with
      multiple biological and behavioral pathways in children that may increase risk
      for later obesity. Little work has detailed the interconnections among these
      mechanisms across development or identified potential moderators of the
      association. Mapping the mechanisms connecting early life stress exposure to
      obesity risk in young children longitudinally should be a priority for obesity
      researchers. Recommendations for developmentally sensitive approaches to research
      that can inform obesity prevention strategies are presented.

PMID- 29656596
TI  - Determination of a suitable low-dose abdominopelvic CT protocol using model-based
      iterative reconstruction through cadaveric study.
AB  - INTRODUCTION: Cadaveric studies provide a means of safely assessing new
      technologies and optimizing scanning prior to clinical validation. Reducing
      radiation exposure in a clinical setting can entail incremental dose reductions
      to avoid missing important clinical findings. The use of cadavers allows
      assessment of the impact of more substantial dose reductions on image quality.
      Our aim was to identify a suitable low-dose abdominopelvic CT protocol for
      subsequent clinical validation. METHODS: Five human cadavers were scanned at one
      conventional dose and three low-dose settings. All scans were reconstructed using
      three different reconstruction algorithms: filtered back projection (FBP), hybrid
      iterative reconstruction (60% FBP and 40% adaptive statistical iterative
      reconstruction (ASIR40)), and model-based iterative reconstruction (MBIR). Two
      readers rated the image quality both quantitatively and qualitatively. RESULTS:
      Model-based iterative reconstruction images had significantly better objective
      image noise and higher qualitative scores compared with both FBP and ASIR40
      images at all dose levels. The greatest absolute noise reduction, between MBIR
      and FBP, of 34.3 HU (equating to a 68% reduction) was at the lowest dose level.
      MBIR reduced image noise and improved image quality even in CT images acquired
      with a mean radiation dose reduction of 62% compared with conventional dose
      studies reconstructed with ASIR40, with lower levels of objective image noise,
      superior diagnostic acceptability and contrast resolution, and comparable
      subjective image noise and streak artefact scores. CONCLUSION: This cadaveric
      study demonstrates that MBIR reduces image noise and improves image quality in
      abdominopelvic CT images acquired with dose reductions of up to 62%.

PMID- 29656597
TI  - Splenic artery as a simple landmark indicating difficulty during laparoscopic
      distal pancreatectomy.
AB  - INTRODUCTION: The use of laparoscopic distal pancreatectomy (LDP) is increasing
      worldwide. It is important for surgeons to predict preoperatively the difficulty
      and risks of a surgery. However, very few reports have evaluated the impact of
      patient or tumor factors on the difficulty of LDP. We aimed to determine the
      predictors of technical difficulties when performing LDP. METHODS: This study
      included 34 patients who underwent LDP. Patient information was obtained
      retrospectively and included age, gender, BMI, primary disease, previous
      abdominal surgery, previous pancreatitis, tumor size, tumor proximity to the
      splenic arterial origin, type of splenic artery (SpA), operative time, blood
      loss, postoperative pancreatic fistula, and length of hospital stay. Univariate
      and multivariate analyses were performed to determine the predictors of a long
      operative time. SpA anatomy was classified into two types based on the
      relationship between its origin and the pancreas. Patients whose SpA origin was
      upward of the pancreatic parenchyma were classified as SpA type 1, whereas
      patients whose SpA origin was covered by the pancreatic parenchyma were
      classified as SpA type 2. RESULTS: Multivariate analysis revealed SpA type 2 to
      be an independent risk factor for a long operation (odds ratio = 9.925; 95%
      confidence interval: 1.461-67.412; P = 0.019). SpA type 2 was related to a longer
      operative time (P < 0.001) and greater intraoperative blood loss (P = 0.001).
      CONCLUSION: Classification according to SpA type is simple and useful for
      predicting technical difficulty when performing LDP.

PMID- 29656598
TI  - Transcatheter tricuspid valve therapies: exploring the dark side of the moon.

PMID- 29656599
TI  - Novel, cost-effective, Cu-doped calcium silicate nanoparticles for bone fracture
      intervention: Inherent bioactivity and in vivo performance.
AB  - Copper (Cu)-doped calcium silicate nanoparticles were synthesized by a wet
      precipitation method as economical bone fracture filler. The aim was to improve
      the overall physicochemical properties, bioactivity, and biological performance
      of the bone fracture filler prepared herein. The synthesized nanoparticles were
      evaluated using X-ray diffraction (XRD), Fourier transform infrared spectroscopy
      (FT-IR), and transmission electron microscopy (TEM). The bioactivity of the
      prepared nanoparticles was investigated after immersion in simulated body fluid
      (SBF) by means of inductively coupled plasma (ICP), SEM coupled with energy
      dispersive X-rays (EDX), and FTIR. The size and bioactivity of the prepared
      nanoparticles after 15 days of immersion in SBF was dependent on the Cu
      concentrations. The fracture healing ability of the fabricated nanoparticles on
      adult aged male Wistar rats was enhanced by the presence of copper. All the
      obtained results are of high relevance for fabricating improved Cu-doped calcium
      silicate nanoparticles (~50 nm) as low cost bone fracture filler. In addition,
      the in vivo study presented complete healing of the tibiae bone with normal
      architecture of bone tissue specifically calcium silicate nanoparticles doped
      with 3% and 5% Cu. Hence, the presence of copper is a promising tactic for
      improving the biological properties of calcium silicate. Therefore, the designed
      nanoparticles have huge potential for the treatment of bone fractures. (c) 2018
      Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2018.

PMID- 29656600
TI  - Long-term efficacy and safety of sucroferric oxyhydroxide in African American
      dialysis patients.
AB  - INTRODUCTION: Sucroferric oxyhydroxide (SFOH) is a non-calcium, iron-based
      phosphate binder that demonstrated sustained serum phosphorus (sP) control, good
      tolerability, and lower pill burden, vs. sevelamer carbonate ("sevelamer"), in a
      Phase 3 study conducted in dialysis patients with hyperphosphatemia. This
      analysis evaluates the efficacy and safety of SFOH and sevelamer among African
      American (AA) patients participating in the trial. METHODS: Post hoc analysis of
      a 24-week, Phase 3, open-label trial (NCT01324128) and its 28-week extension
      study (NCT01464190). Patients were randomized 2:1 to SFOH (1.0-3.0 g/day) or
      sevelamer (2.4-14.4 g/day) for up to 52 weeks. FINDINGS: Of 549 patients who
      completed the Phase 3 study and extension, 100 (18.2%) AA patients were eligible
      for efficacy analysis (SFOH, n = 48; sevelamer, n = 52). sP concentrations
      decreased rapidly and comparably with both treatments by Week 8 (mean +/-
      standard deviation change from baseline: -1.9 +/- 1.9 mg/dL for SFOH and -2.2 +/-
      1.8 mg/dL for sevelamer). These reductions were maintained for 52 weeks (-2.1 +/-
      2.6 and -2.1 +/- 1.6 mg/dL) and achieved with a lower mean pill burden (3.4 +/-
      1.4 vs. 7.6 +/- 2.9 tablets/day) with SFOH vs. sevelamer. Treatment adherence
      rates (adherence within 70%-120% of expected medication intake) were 79.2% with
      SFOH and 59.6% with sevelamer. The proportion of patients reporting serious
      adverse events (AEs) was 27.7% with SFOH and 30.7% with sevelamer. More patients
      withdrew due to treatment-emergent AEs with SFOH vs. sevelamer (18.5% vs. 8.0%).
      The most common AEs with both treatments were gastrointestinal-related: diarrhea
      and discolored feces with SFOH, and nausea, vomiting, and constipation with
      sevelamer. DISCUSSION: SFOH is an efficacious and well-tolerated treatment for
      hyperphosphatemia in AA dialysis patients, with a lower pill burden and an
      improved adherence rate vs. sevelamer. These findings were consistent with the
      wider US patient population and the overall study population.

PMID- 29656601
TI  - Culture-independent analysis of hydrocarbonoclastic bacterial communities in
      environmental samples during oil-bioremediation.
AB  - To analyze microbial communities in environmental samples, this study combined
      Denaturing Gradient Gel Electrophoresis of amplified 16S rRNA-genes in total
      genomic DNA extracts from those samples with gene sequencing. The environmental
      samples studied were oily seawater and soil samples, that had been bioaugmented
      with natural materials rich in hydrocarbonoclastic bacteria. This molecular
      approach revealed much more diverse bacterial taxa than the culture-dependent
      method we had used in an earlier study for the analysis of the same samples. The
      study described the dynamics of bacterial communities during bioremediation. The
      main limitation associated with this molecular approach, namely of not
      distinguishing hydrocarbonoclastic taxa from others, was overcome by consulting
      the literature for the hydrocarbonoclastic potential of taxa related to those
      identified in this study. By doing so, it was concluded that the
      hydrocarbonoclastic bacterial taxa were much more diverse than those captured by
      the culture-dependent approach. The molecular analysis also revealed the frequent
      occurrence of nifH-genes in the total genomic DNA extracts of all the studied
      environmental samples, which reflects a nitrogen-fixation potential. Nitrogen
      fertilization is long known to enhance microbial oil-bioremediation. The study
      revealed that bioaugmentation using plant rhizospheres or soil with long history
      of oil-pollution was more effective in oil-removal in the desert soil than in
      seawater microcosms.

PMID- 29656602
TI  - Evolution of fundus autofluorescence patterns over time in patients with chronic
      central serous chorioretinopathy.
AB  - PURPOSE: To determine the evolution of fundus autofluorescence (FAF) patterns in
      chronic central serous chorioretinopathy (CSCR) over time. METHODS: We
      retrospectively studied the changes in FAF patterns over time in 157 eyes of 112
      patients with chronic CSCR using the Heidelberg Retina Angiography with a 488-nm
      excitation light and a 500-nm cutoff barrier filter. RESULTS: The mean duration
      of follow-up was 37.2 months. The most common baseline pattern was that of
      granular hypoautofluorescence (51.0%). The earliest change in chronic CSCR is
      diffuse hyperautofluorescence and it occurs approximately 4 months after the
      reported first episode. The most common change observed at this stage is a change
      within areas of hyperautofluorescence where hyper-reflective dots appeared or
      disappeared. Change in FAF patterns from areas of hyperautofluorescence to
      hypoautofluorescence was slow. Only 25% of eyes showed such a change in pattern
      by 36 months. It takes an average of 24 months for granular hypoautofluorescent
      pattern to develop confluent hypoautofluorescence. There were no predictive
      patterns for the development of confluent CSCR. CONCLUSION: Fundus
      autofluorescence (FAF) changes in CSCR evolve very gradually and so is not a good
      outcome measure for clinical trials.

PMID- 29656603
TI  - Improvement and application of the PCPF-1@SWAT2012 model for predicting pesticide
      transport: a case study of the Sakura River watershed.
AB  - BACKGROUND: The Soil and Water Assessment Tool combined with Pesticide
      Concentration in Paddy Field (PCPF-1@SWAT) model was previously developed to
      simulate the fate and transport of rice pesticides in watersheds. However, the
      current model is deficient in characterizing the rice paddy area and is
      incompatible with the ArcSWAT2012 program. In this study, we modified the
      original PCPF-1@SWAT model to develop a new PCPF-1@SWAT2012 model to address the
      deficiency in the rice paddy area and utilizing the ArcSWAT2012 program. Next,
      the new model was applied to the Sakura River watershed, Ibaraki, Japan in order
      to simulate the transport of four herbicides: mefenacet, pretilachlor,
      bensulfuron-methyl and imazosulfuron. RESULTS: The results showed that the water
      flow rate simulated by PCPF1@SWAT2012 was similar with the observed data. The
      calculated Nash-Sutcliffe efficiency coefficient (NSE) (0.73) and percent bias
      (PBIAS) (-20.38) suggested satisfactory performance of the model. In addition,
      the concentrations of herbicides simulated by the PCPF-1@SWAT2012 model were in
      good agreement with the observed data. The statistical indices NSE and root mean
      square error (RMSE) estimated for mefenacet (0.69 and 0.18, respectively),
      pretilachlor (0.86 and 0.18, respectively), bensulfuronmethyl (0.46 and 0.21,
      respectively) and imazosulfuron (0.64 and 0.28, respectively) indicated
      satisfactory predictions. CONCLUSION: The PCPF-1@SWAT2012 model is capable of
      simulating well the water flow rate and transport of herbicides in this
      watershed, comprising different land use types, including a rice paddy area. (c)
      2018 Society of Chemical Industry.

PMID- 29656604
TI  - Corrigendum.

PMID- 29656605
TI  - Corrigendum.

PMID- 29656606
TI  - A meta-analysis on the surgical management of paraganglioma of the carotid body
      per Shamblin class.
AB  - OBJECTIVE: The aim of this study was to evaluate the risk associated with
      different types of surgery for carotid body paraganglioma of different Shamblin
      class. A meta-analysis was conducted to evaluate per tumour class, the local
      control, cranial nerve damage and complication rates of different techniques
      using internal carotid artery (ICA) and external carotid artery (ECA) ligation,
      clamping or bypassing, as well as the craniocaudal vs caudocranial techniques.
      DESIGN: A meta-analysis is conducted after a systematic search in PubMed and the
      Cochrane library, in accordance with the PRISMA guidelines. MAIN OUTCOME
      MEASURES: Local control, cranial nerve damage, complications, function recovery.
      RESULTS: Out of 3565 articles, 27 were selected. The overall quality of evidence
      of studies was low. Cranial nerve damage (3%, 17% and 39%) and complication rates
      (0%, 1% and 10%) were significantly related to Shamblin class (class 1, 2 and 3,
      respectively, P < .01). For class 3 tumours, an increased risk of complications
      was found associated with routine ICA manipulation/reconstruction (RR 3.12 with a
      95% CI of 1.29-7.59), as well as a trend towards enhanced risk of routine ECA
      ligation (RR 3.48 with a 95% CI of 0.88-13.81). CONCLUSIONS: For class 1 and 2
      tumours, surgery seems a viable treatment option. For class 3 tumours, morbidity
      in terms of cranial nerve deficit and complications is considerable;
      particularly, the use of ICA manipulation/reconstruction and potentially ECA
      ligation seem to be accompanied by high stroke incidence.

PMID- 29656607
TI  - Expert Agreement in the Interpretation of Lung Ultrasound Studies Performed on
      Mechanically Ventilated Patients.
AB  - OBJECTIVES: Although lung ultrasound (US) has been shown to have high diagnostic
      accuracy in patients presenting with acute dyspnea, its precision in critically
      ill patients is unknown. We investigated common areas of agreement and
      disagreement by studying 6 experts as they interpreted lung US studies in a
      cohort of intensive care unit (ICU) patients. METHODS: A previous study by our
      group asked experts to rate the quality of 150 lung US studies performed by 10
      novices in a population of mechanically ventilated patients. For this study,
      experts were asked to interpret them without the clinical context, reporting the
      presence of pneumothorax, interstitial syndrome, consolidation, atelectasis, or
      pleural effusion. RESULTS: The rate of expert agreement depended on how it was
      defined, ranging from 51% (with a strict definition of agreement) to 57% (with a
      more liberal definition). Removing cases involving lung consolidation (the most
      common source of disagreement) improved the rates of agreement to 69% and 86%,
      respectively. CONCLUSIONS: The frequency of agreement was lower than might have
      been expected in this study. Several potential reasons are identified, chief
      among them the fact that ICU patients often develop multiple pulmonary insults,
      making agreement on a specific primary diagnosis challenging. This finding
      suggests that the utility of lung US in identifying the main contributing lung
      condition in ICU patients may be lower than in dyspneic patients encountered in
      the emergency department. It also raises the possibility that the clinical
      context is more important for lung US than other imaging modalities.

PMID- 29656608
TI  - Combined therapy for critical limb ischaemia: Biomimetic PLGA microcarriers
      potentiates the pro-angiogenic effect of adipose tissue stromal vascular fraction
      cells.
AB  - We propose a regenerative solution in the treatment of critical limb ischaemia
      (CLI). Poly-lactic/glycolic acid microcarriers were prepared and coated with
      laminin to be sterilized through gamma-irradiation of 25 kGy at low temperature.
      Stromal vascular fraction (SVF) cells were extracted through enzymatic digestion
      of adipose tissue. Streptozotocin-induced diabetic mice underwent arteriotomy and
      received an administration of SVF cells combined or not with biomimetic
      microcarriers. Functional evaluation of the ischaemic limb was then reported, and
      tissue reperfusion was evaluated through fluorescence molecular tomography.
      Microcarriers were stable and functional after gamma-irradiation until at least
      12 months of storage. Mice that received an injection of SVF cells in the
      ischaemic limb have 22% of supplementary blood supply within this limb 7 days
      after surgery compared with vehicle, whereas no difference was observed at Day
      14. With the combined therapy, the improvement of blood flow is significantly
      higher compared with vehicle, of about 31% at Day 7 and of about 11% at Day 14.
      Injection of SVF cells induces a significant 27% decrease of necrosis compared
      with vehicle. This effect is more important when SVF cells were mixed with
      biomimetic microcarriers: -37% compared with control. Although SVF cells
      injection leads to a non-significant 22% proprioception recovery, the combined
      therapy induces a significant recovery of about 27% compared with vehicle. We
      show that the combination of SVF cells from adipose tissue with laminin-coated
      poly-lactic/glycolic acid microcarriers is efficient for critical limb ischaemia
      therapy in a diabetic mouse model.

PMID- 29656609
TI  - Monocyte function in patients with myelodysplastic syndrome.
AB  - Myelodysplastic syndrome (MDS) is a malignant hematopoietic stem cell disorder
      that frequently evolves into acute myeloid leukemia (AML). Patients with MDS are
      prone to infectious complications, in part due to the presence of severe
      neutropenia and/or neutrophil dysfunction. However, not all patients with
      neutropenia become infected, suggesting that other immune cells may compensate in
      these patients. Monocytes are also integral to immunologic defense; however, much
      less is known about monocyte function in patients with MDS. In the current study,
      we monitor the composition of peripheral blood monocytes and several aspects of
      monocyte function in MDS patients, including HLA-DR expression, LPS-induced
      inflammatory cytokine production, and phagocytosis. We find that monocytes from
      MDS patients exhibit relatively normal innate immune functions compared to
      monocytes from healthy control subjects. We also find that HLA-DR expression is
      moderately increased in monocytes from MDS patients. These results suggest that
      monocytes could compensate for other immune deficits in MDS patients to help
      fight infection. We also find that the range of immune functions in monocytes
      from MDS patients correlates with several key clinical parameters, including
      blast cell count, monocyte count, and revised International Prognostic Scoring
      System score, suggesting that disease severity impacts monocyte function in MDS
      patients.

PMID- 29656610
TI  - Fipronil recognition by the FA1 site of human serum albumin.
AB  - Fipronil is a broad-spectrum pesticide widely used in agriculture, horticulture,
      and forestry. Because fipronil can cause a variety of toxic effects in animals
      and humans, its use is authorized as a pesticide in veterinary medicinal products
      for pets, but not for the treatment of livestock animals whose products are
      intended for consumption. Recently, however, the presence of fipronil residues
      has been detected in the eggs and meat of layer hens from farms located in
      different European countries. Given the relevance of fipronil toxicity for human
      health, it is important to gain information concerning its fate in the human
      body, including its binding mode to human serum albumin (HSA), the most abundant
      protein in plasma. Here, the inhibition of heme-Fe(III) binding to the fatty acid
      site 1 (FA1) of HSA by fipronil is reported. Docking simulations support
      functional data, indicating that the FA1 site is the preferential cleft for
      fipronil recognition by HSA. The affinity of fipronil for HSA (Kf  = 1.9 * 10-6 
      M, at pH 7.3, and 20.0 degrees C) may be relevant in vivo. Indeed, HSA could play
      a pivotal role in fipronil transport and scavenging, thus reducing the pesticide
      free plasmatic levels, with consequent reduced systemic toxicity. In turn,
      fipronil binding to the FA1 site of HSA could impair the recognition of
      endogenous and exogenous molecules.

PMID- 29656611
TI  - Modified breath-hold compressed-sensing 3D MR cholangiopancreatography with a
      small field-of-view and high resolution acquisition: Clinical feasibility in
      biliary and pancreatic disorders.
AB  - BACKGROUND: Compressed-sensing (CS) accelerated 3D MR cholangiopancreatography
      (MRCP) could be acquired in both navigator-triggered (NT) and breath-hold (BH)
      mode, but the latter has been considered inferior in depicting pancreatic duct
      and diagnosing pancreatic duct-related diseases. PURPOSE: To prospectively
      evaluate the clinical feasibility of a modified 3D BH-CS-MRCP prototype protocol
      with small field-of-view (FOV) and higher spatial resolution, and to compare its
      performance to the original BH-CS-MRCP and NT-CS-MRCP. STUDY TYPE: Prospective
      cohort study. POPULATION: Eighty-two patients with suspected pancreaticobiliary
      diseases (46 male, median age, 55 years, range, 16-79 years), including seven
      noncooperative patients. FIELD STRENGTH/SEQUENCE: 3T, CS-MRCP. ASSESSMENT: Three
      protocols were performed in random order in each patient. Acquisition time of
      each protocol was recorded. Image quality, background suppression, duct
      visibility, and diagnostic confidence with duct anatomic variations and duct
      related pathologies were rated on a 5-point scale by two blinded radiologists
      independently. STATISTICAL TESTS: The Wilcoxon signed-rank test was used to
      compare the intraindividual difference. Interobserver agreement was determined
      using kappa coefficients. The diagnostic performance was calculated using
      receiver operating characteristic curves. RESULTS: Acquisition time was 17
      seconds for both BH-CS-MRCP protocols, and 127.5 +/- 36.9 seconds for NT-CS-MRCP.
      In 75 cooperative patients, the incidence of major artifacts was low for all
      protocols (5.3-8.0%). Background suppression was similar with the two BH-CS-MRCP
      protocols (3.67 +/- 0.77 for original BH-CS-MRCP and 3.70 +/- 0. 57 for modified
      BH-CS-MRCP, respectively), both inferior to the NT-CS-MRCP protocol (4.41 +/-
      0.68, P < 0.001 for both). Modified BH-CS-MRCP and NT-CS-MRCP depicted pancreatic
      duct and second-level branches of biliary duct better than original BH-CS-MRCP
      (all P < 0.01). The diagnostic performance for detecting bile duct abnormalities
      was similar for all protocols (P = 0.53-0.87), whereas for detecting pancreatic
      duct abnormalities, modified BH-CS-MRCP and NT-CS-MRCP had significantly better
      performance compared to original BH-CS-MRCP (both P < 0.01). In seven
      noncooperative patients, NT-CS-MRCP had superior image quality than both BH
      protocols (both P < 0.01). DATA CONCLUSION: Modified BH-CS-MRCP is feasible for
      pancreatic and biliary disorders. NT-CS-MRCP might be more useful in
      noncooperative patients. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J.
      Magn. Reson. Imaging 2018;47:1389-1399.

PMID- 29656612
TI  - Counterintuitive effects of global warming-induced wind patterns on primary
      production in the Northern Humboldt Current System.
AB  - It has been hypothesized that global warming will strengthen upwelling-favorable
      winds in the Northern Humboldt Current System (NHCS) as a consequence of the
      increase of the land-sea thermal gradient along the Peruvian coast. The effect of
      strengthened winds in this region is assessed with the use of a coupled physical
      biogeochemical model forced with projected and climatological winds. Strengthened
      winds induce an increase in primary production of 2% per latitudinal degree from
      9.5 degrees S to 5 degrees S. In some important coastal upwelling sites primary
      production is reduced. This is due to a complex balance between nutrient
      availability, nutrient use efficiency, as well as eddy- and wind-driven factors.
      Mesoscale activity induces a net offshore transport of inorganic nutrients, thus
      reducing primary production in the coastal upwelling region. Wind mixing, in
      general disadvantageous for primary producers, leads to shorter residence times
      in the southern and central coastal zones. Overall, instead of a proportional
      enhancement in primary production due to increased winds, the NHCS becomes only
      5% more productive (+5 mol C m-2 year-1 ), 10% less limited by nutrients and 15%
      less efficient due to eddy-driven effects. It is found that regions with a
      initial strong nutrient limitation are more efficient in terms of nutrient
      assimilation which makes them more resilient in face of the acceleration of the
      upwelling circulation.

PMID- 29656613
TI  - siRNA Modified with 2'-Deoxy-2'-C-methylpyrimidine Nucleosides.
AB  - (2'S)-2'-Deoxy-2'-C-methyluridine and (2'R)-2'-deoxy-2'-C-methyluridine were
      incorporated in the 3'-overhang region of the sense and antisense strands and in
      positions 2 and 5 of the seed region of siRNA duplexes directed against Renilla
      luciferase, whereas (2'S)-2'-deoxy-2'-C-methylcytidine was incorporated in the 6
      position of the seed region of the same constructions. A dual luciferase reporter
      assay in transfected HeLa cells was used as a model system to measure the IC50
      values of 24 different modified duplexes. The best results were obtained by the
      substitution of one thymidine unit in the antisense 3'-overhang region by (2'S)-
      or (2'R)-2'-deoxy-2'-C-methyluridine, reducing IC50 to half of the value observed
      for the natural control. The selectivity of the modified siRNA was measured, it
      being found that modifications in positions 5 and 6 of the seed region had a
      positive effect on the ON/OFF activity.

PMID- 29656614
TI  - 6-Minute walk test predicts prolonged hospitalization in patients undergoing
      transcatheter mitral valve repair by MitraClip.
AB  - BACKGROUND: The 6-minute walk test (6MWT) is a simple functional test that can
      predict exercise capacity and is widely employed to assess treatment outcomes.
      Although mortality with transcatheter mitral valve repair (TMVr) using the
      MitraClip (Abbott Vascular, Menlo Park, CA) is significantly less than for open
      mitral valve surgery in high-risk patients, identifying which patient will
      benefit the most from TMVr remains a concern. There are limited prognostic
      metrics guiding patient selection and, no studies have reported relationship
      between prolonged hospitalization and 6MWT. This study aimed to determine if the
      6MWT can predict prolonged hospitalization in patients undergoing TMVr by
      MitraClip. METHODS: We retrospectively reviewed 162 patients undergoing 6MWT
      before TMVr. Patients were divided into three groups according to the 6MWT
      distance (6MWTD) using the median (6MWTD >=219 m, 6MWTD <219 m, and Unable to
      Walk). Multivariate logistic regression model was applied to select the
      demographic characteristics that were associated with the prolonged
      hospitalization defined as total length of stay >=4 days in the study. RESULTS:
      We found that 6MWT (odds ratio 3.64, 95% confidence interval 2.03-6.52, P <
      0.001) was independently associated with prolonged hospitalization after
      adjustment in multivariate analysis. Area under the curve of 6MWT for predicting
      prolonged hospitalization was 0.79 (95% confidence interval 0.72-0.85).
      CONCLUSIONS: Our study demonstrates that 6MWT was independently associated with
      prolonged hospitalization in patients with TMVr, and has a good discriminatory
      performance for predicting prolonged hospitalization.

PMID- 29656615
TI  - The Korean Spinal Neurosurgery Society: Let's Jump Into the World of Neurospine.

PMID- 29656616
TI  - The Neurospinal Society of Japan: For a Start of Our New Journal.

PMID- 29656618
TI  - Taiwan Neurosurgical Spine Society: Move Together in "Neurospine" Toward Clinical
      and Academic Success.

PMID- 29656617
TI  - Neurospine: Harmonious Launch of a New Intellectual Odyssey.

PMID- 29656619
TI  - Impact of Resident Involvement in Neurosurgery: An American College of Surgeons'
      National Surgical Quality Improvement Program Database Analysis of 33,977
      Patients.
AB  - OBJECTIVE: There is conflicting and limited literature on the effect of
      intraoperative resident involvement on surgical outcomes. Our study assessed
      effects of resident involvement on outcomes in patients undergoing neurosurgery.
      METHODS: We identified 33,977 adult neurosurgical cases from 374 hospitals in the
      2006-2012 National Surgical Quality Improvement Program, a prospectively
      collected national database with established reproducibility and validity.
      Outcomes were compared according to resident involvement before and after 1:1
      matching on procedure and perioperative risk factors. RESULTS: Resident
      involvement was documented in 13,654 cases. We matched 10,170 resident-involved
      cases with 10,170 attending-alone. In the matched sample, resident involvement
      was associated with increased surgery duration (average, 34 minutes) and slight
      increases in odds for prolonged hospital stay (odds ratio, 1.2; 95% confidence
      interval [CI], 1.2-1.3) and complications (odds ratio, 1.2; 95% CI, 1.1-1.3)
      including infections (odds ratio, 1.4; 95% CI, 1.2-1.7). Increased risk for
      infections persisted after controlling for surgery duration (odds ratio, 1.3; 95%
      CI, 1.1-1.5). The majority of cases were spine surgeries, and resident
      involvement was not associated with morbidity or mortality for malignant tumor
      and aneurysm patients. Training level of residents was not associated with
      differences in outcomes. CONCLUSION: Resident involvement was more common in
      sicker patients undergoing complex procedures, consistent with academic centers
      undertaking more complex cases. After controlling for patient and intraoperative
      characteristics, resident involvement in neurosurgical cases continued to be
      associated with longer surgical duration and slightly higher infection rates.
      Longer surgery duration did not account for differences in infection rates.

PMID- 29656620
TI  - The Effect of Recombinant Tyrosine Hydroxylase Expression on the Neurogenic
      Differentiation Potency of Mesenchymal Stem Cells.
AB  - OBJECTIVE: Tyrosine hydroxylase (TH) is a rate-limiting enzyme in dopamine
      synthesis, making the enhancement of its activity a target for ensuring
      sufficient dopamine levels. Rat bone marrow mesenchymal stem cells (rBM-MSCs) are
      known to synthesize TH after differentiating into neuronal cells through chemical
      induction, but the effect of its ectopic expression on these cells has not yet
      been determined. This study investigated the effects of ectopic recombinant TH
      expression on the stemness characteristics of rBM-MSCs. METHODS: After cloning, a
      cell line with stable TH expression was maintained, and the proliferation, the
      gene expression profile, and differentiation potential of rBM-MSCs were analyzed.
      Analysis of the cells showed an increment in the proliferation rate that could be
      reversed by the neutralization of TH. RESULTS: The constitutive expression of TH
      in rBM-MSCs was successfully implemented, without significantly affecting their
      osteogenic and adipogenic differentiation potential. TH expression improved the
      expression of other neuronal markers, such as glial fibrillary acidic protein,
      beta-tubulin, nestin, and c-Fos, confirming the neurogenic differentiation
      capacity of the stem cells. The expression of brain-derived neurotrophic factor
      (BDNF) and ciliary neurotrophic factor (CNTF) significantly increased after the
      chemical induction of neurogenic differentiation. CONCLUSION: In this study, the
      expression of recombinant TH improved the neuroprotective effect of MSCs by
      upregulating the expression of BDNF and CNTF. Although the neuronal markers were
      upregulated, the expression of recombinant TH alone in rBM-MSCs was not
      sufficient for MSCs to differentiate into neurogenic cell lines.

PMID- 29656621
TI  - Effect of Myoarchitectonic Spinolaminoplasty on Concurrent Hypertension in
      Patients With Cervical Spondylotic Myelopathy.
AB  - OBJECTIVE: When treating patients with cervical spondylotic myelopathy (CSM), we
      often note amelioration in concomitant hypertension after surgery. To assess the
      effects of surgery and the mechanisms thereof, blood pressure (BP) and
      parasympathetic nervous activity were monitored prospectively in CSM patients
      undergoing surgery. METHODS: Sixty-eight consecutive CSM patients who underwent
      surgery with myoarchitectonic spinolaminoplasty were enrolled. BP and
      electrocardiography were recorded preoperatively and at 1, 3, and 6 months
      postoperatively. Forty-six patients completed the scheduled follow-ups and were
      analyzed. Preoperatively, 17 had a mean BP higher than 100 mmHg (the HT group)
      and 12 had hypertension despite taking medication (the HT-refractory group). To
      evaluate alterations in parasympathetic function, the coefficient of variation of
      the RR interval (CVRR) was evaluated. RESULTS: A significant BP reduction was
      observed in the HT group 6 months after surgery, but not in the normotensive
      group (n=29). The effect was more remarkable in the HT-refractory group. A
      transient BP increase at 1 and 3 months after surgery was observed in all groups.
      Comparisons were made between groups classified by age (over 65 years or younger
      than 60 years) and the presence or absence of an intramedullary hyperintense T2
      signal on magnetic resonance imaging, but no significant differences were
      detected. Measurements of CVRR did not significantly differ between the groups
      over the course of follow-up. CONCLUSION: Hypertension coexisting with CSM can be
      ameliorated after surgical treatment. The effect is likely to be mediated by
      moderation of sympathetic activity, rather than parasympathetic activation. We
      believe that a combination of adequate decompression of the spinal cord and
      relief from musculoskeletal stresses effectuate this moderation.

PMID- 29656622
TI  - Minimally Invasive Spinal Surgery for Adult Spinal Deformity.
AB  - The purpose of this review is to present the current techniques and outcomes of
      adult spine deformity (ASD) surgery using the minimally invasive spine surgery
      (MISS) approach. We performed a systemic search of PubMed for literature
      published through January 2018 with the following terms: "minimally invasive
      spine surgery," "adult spinal deformity," and "degenerative scoliosis." Of the
      138 items that were found through this search, 57 English-language articles were
      selected for full-text review. According to the severity of the deformity and the
      symptoms, various types of MISS have been utilized, such as MISS decompression,
      circumferential MISS, and hybrid surgery. With proper indications, the MISS
      approach achieved satisfactory clinical and radiological outcomes for ASD, with
      reduced complication rates. Future studies should aim to define clear indications
      for the application of various surgical options.

PMID- 29656623
TI  - Superior and Middle Cluneal Nerve Entrapment as a Cause of Low Back Pain.
AB  - Low back pain (LBP) is encountered frequently in clinical practice. The superior
      and the middle cluneal nerves (SCN and MCN) are cutaneous nerves that are purely
      sensory. They dominate sensation in the lumbar area and the buttocks, and their
      entrapment around the iliac crest can elicit LBP. The reported incidence of SCN
      entrapment (SCN-E) in patients with LBP is 1.6%-14%. SCN-E and MCN entrapment
      (MCN-E) produce leg symptoms in 47%-84% and 82% of LBP patients, respectively. In
      such patients, pain is exacerbated by lumbar movements, and the symptoms mimic
      radiculopathy due to lumbar disorder. As patients with failed back surgery or
      Parkinson disease also report LBP, the differential diagnosis must include those
      possibilities. The identification of the trigger point at the entrapment site and
      the disappearance of symptoms after nerve block are diagnostically important. LBP
      due to SCN-E or MCN-E can be treated less invasively by nerve block and
      neurolysis. Spinal surgeons treating patients with LBP should consider SCN-E or
      MCN-E.

PMID- 29656624
TI  - Health Care Burden of Spinal Diseases in the Republic of Korea: Analysis of a
      Nationwide Database From 2012 Through 2016.
AB  - OBJECTIVE: This study aimed to determine the incidence and analyze trends related
      to spinal diseases based on a national database in the Republic of Korea (ROK)
      and to elucidate the healthcare burden that will serve as a useful resource for
      researchers, clinicians, and patients. METHODS: This study was a retrospective
      analysis of data obtained from Healthcare Bigdata Hub, the Korean Statistical
      Information Service, and Open Data Portal from 2012 through 2016. The main
      disease codes for spinal diseases (M40-M54) were used for identification of these
      conditions. RESULTS: The overall annual incidence rates for spinal disease in the
      ROK was median 15,877 (men, 13,181; women, 18,588) per 100,000 population, and
      sex ratio was 1:1.41 (p<0.01). The incidence rate and annual costs per patient
      increased by 7.6% and 14.7% over 5 years continuously, respectively. The age
      adjusted incidence rate increased with age; the highest rates were 42.6% in the
      75-79 years group. Patients older than 65 years old accounted for median 31.0% of
      number of patients and 40.1% of medical expenses over 5 years. Lumbar disc
      herniation (M51) and spinal stenosis (M48) might accounted for both the highest
      incidence and medical expenses in patients under the age of 60 and over 60 years,
      respectively. CONCLUSION: The incidence and medical expenditures of spinal
      disease increased continuously. As the population of ROK in aging, the incidence
      and medical expenditures due to spondylosis and stenosis (M48) for the old are
      also increasing. The social burden of spinal diseases in elder patients needs to
      be prudently considered in health policy makers.

PMID- 29656625
TI  - Swiss-Korean Exchange Program in Neurosurgical Spine Surgery: Experience of the
      First Year.

PMID- 29656626
TI  - ASIA SPINE: The Past, Present, and Future.
AB  - The sharing of international academic accomplishment and friendship is important;
      furthermore, to better understand and anticipate the future, we should look back
      and remember where we started. Regarding ASIA SPINE, the authors aimed to record
      how the pioneers of Asian spinal surgery started this spine meeting series more
      than 20 years ago and that later developed into the present state of the
      conference. The authors will also explore the possible future of this conference.
      In June 1996, when Professor Hiroshi Nakagawa organized the 11th Annual Meeting
      of the Japanese Society of Spinal Surgery, spinal neurosurgeons from Korea and
      Japan including Professor Young Soo Kim, Professor Jung Keun Suh, and Professor
      Nakagawa discussed the establishment of a multinational conference on spinal
      surgery via a partnership between the 2 countries. Finally, from September 18 to
      20, 1997, the First Biennial Meeting of the Japan-Korea Conference on Spinal
      Surgery was held in Nagoya, Japan, with Professor Hiroshi Nakagawa as the first
      organizing President. From then, a biennial meeting was held every other year in
      Korea or Japan until 2009. In September 2010, the next generation of spinal
      neurosurgeons decided to organize the first meeting of ASIA SPINE in Incheon,
      Korea, in order to represent all Asian spine specialists. This meeting has been
      since held annually around the region including in Taiwan. Remembering the
      pioneers in the field of spinal surgery is invaluable and extremely important.
      The authors hope that interest in ASIA SPINE will further expand to other nations
      in Asia who have advanced philosophies and refined technologies. We wish ASIA
      SPINE continued success and the ability to promote prolonged international
      friendship among the Asian countries .

PMID- 29656627
TI  - Ossification of the Posterior Longitudinal Ligament in Cervical Spine:
      Prevalence, Management, and Prognosis.
AB  - Ossification of the posterior longitudinal ligament (OPLL) in the cervical spine
      and related neurological complications are not uncommon in East Asian countries.
      The estimated prevalence of cervical OPLL-related hospitalization is 7.7 per
      100,000 person-years in Taiwan, and higher incidence rates have been observed in
      elderly and male patients. Although cervical OPLL is frequently insidious, it can
      eventually cause myelopathy and predispose patients to spinal cord injury (SCI).
      There are multiple options for managing cervical OPLL, ranging from observation
      to many kinds of surgical procedures, including posterior laminoplasty,
      laminectomy with or without fusion, anterior corpectomy with or without
      instrumentation, and circumferential decompression and fusion. None of these
      surgical approaches is free of complications. However, to date, there is still a
      lack of consensus regarding the choice of the surgical approach and the timing of
      surgical intervention. Cervical SCI and related neurological disabilities are
      more likely to occur in OPLL patients, who should therefore be cautioned
      regarding the possibility of a subsequent SCI if treated without surgery. This
      article aimed to review the prevalence, management strategies, and prognosis of
      cervical OPLL.

PMID- 29656628
TI  - Cerebral Thromboembolic Events During Anterior Cervical Spine Surgery:
      Retrospective Case Series Study With Diffusion-Weighted Magnetic Resonance
      Imaging Follow-up in the Immediate Postoperative Period.
AB  - OBJECTIVE: We evaluated the efficacy of diffusion-weighted magnetic resonance
      imaging (DW-MRI) in detecting perioperative cerebral thromboembolic events after
      anterior cervical discectomy and fusion (ACDF). METHODS: This retrospective case
      series included 51 consecutive patients that underwent ACDF. To assess baseline
      presence of plaque or stenosis, all patients were assessed for risk factors of
      cerebrovascular events and underwent carotid ultrasound preoperatively and
      cerebral DW-MRI was performed in all patients postoperatively, with areas of high
      signal intensity interpreted as a cerebral thromboembolic event. RESULTS: One
      male patient who underwent a C4/5 ACDF had a focal diffusion abnormality on DW
      MRI concerning for cerebral thromboembolic events in the right posterior cerebral
      artery territory. He remained asymptomatic and did not display related
      neurological symptoms, such as visual deficits. CONCLUSION: Asymptomatic cerebral
      thromboembolic events can be detected by DW-MRI after ACDF. The incidence of such
      events remains very rare despite the direct manipulation and associated
      alteration of common carotid artery flow dynamics.

PMID- 29656629
TI  - Differences in Cervical Sagittal Alignment Changes in Patients Undergoing
      Laminoplasty and Anterior Cervical Discectomy and Fusion.
AB  - OBJECTIVE: Anterior cervical discectomy and fusion (ACDF) and laminoplasty (LP)
      are the most commonly performed procedures for degenerative cervical spondylosis.
      Cervical sagittal alignment (CSA) has recently been studied as an important
      predictor of clinical and radiological outcomes. The data from previous studies
      are insufficient for analysis using the recently designed CSA parameters, T1
      slope (T1s), and T1s minus cervical angle (T1sCA). METHODS: We retrospectively
      collected data from patients who underwent ACDF and LP from January 2013 to May
      2016. The CSA parameters included CA, sagittal vertical axis, T1s, and T1sCA.
      T1sCA values were used to evaluate the preoperative cervical balance (T1sCA>20
      degrees : imbalance). Clinical results were evaluated using the neck disability
      index (NDI) and recovery rate (RR) according to the Japanese Orthopedic
      Association scoring system. RESULTS: We analyzed the data of 72 patients (ACDF,
      n=39; LP, n=33). Imbalance on ACDF was associated with an increase in CA
      (balance: preoperative [PRE], 15.64 degrees  -> follow-up [F/U], 15.74 degrees ,
      p=0.953; imbalance: PRE, -1.14 degrees  -> F/U, 8.045 degrees , p=0.008), whereas
      balance on LP was associated with a significant decrease in CA (balance: PRE,
      16.26 degrees -> F/U, 11.59 degrees , p=0.009; imbalance: PRE, 5.36 degrees ->
      F/U, 2.38 degrees , p=0.249). No significant difference was found in the RR and
      NDI changes in the ACDF group based on balance, but a significant difference was
      found in RR in the LP group (balance: 61.65%+/-19.88%, imbalance: 46.90%+/
      15.71%, p=0.046). CONCLUSION: We found a significant difference in postoperative
      alignment in cases of ACDF and LP according to preoperative cervical sagittal
      balance. The postoperative clinical results of the LP group were more affected by
      F/U alignment than by the degree of alignment change.

PMID- 29656630
TI  - Etiopathogenesis of Traumatic Spinal Epidural Hematoma.
AB  - Spinal epidural hematoma (SEH) is a rare cause of nerve root or cord compression;
      its pathogenesis is not always clearly recognizable. The aim of this paper was to
      investigate possible etiopathological factors in a consecutive series of patients
      affected by traumatic SEH treated at our institution. Seven patients with
      neurologic impairment due to traumatic SEH were retrospectively analyzed after
      diagnosis and surgical treatment. Thoracic localization was found in 5 cases, and
      lumbar and cervical localization were found in 1 patient each. One patient was
      affected by ankylosing spondylitis and one by diffuse idiopathic skeletal
      hyperostosis. SEH was associated with spine fractures in 6 cases. Only 2 cases of
      traumatic SEH resulted from high-energy trauma. All patients underwent surgical
      decompression within 24 hours after admittance to the hospital. Three patients
      recovered completely, 3 remained paraplegic, and 1 remained monoplegic. Several
      concomitant conditions are suggested to be predisposing factors for the
      development of SEH, although its inherent mechanism is still unknown. Two
      patients in the present series were affected by rheumatologic disorders,
      confirming the elevated incidence of hematomas in such patients compared to the
      normal population. Three very unusual cases of SEH occurred in senile patients
      affected by osteoporotic fractures. Early diagnosis and urgent decompression of
      the hematoma remain mandatory.

PMID- 29656632
TI  - Long-term Survival in Patients Treated with a Robotic Radiosurgical Device for
      Liver Metastases.
AB  - Purpose: The treatment of liver metastases with local procedures is a fast
      progressing field. For the most, long-term survival data is missing raising
      questions with regard to the efficacy of such modalities when compared to
      surgical resection. Radiosurgery using the CyberKnife device enables the
      treatment of liver lesions with a single-session approach. Here we present long
      term survival data to explore the curative potential of this strategy. Materials
      and Methods: Patients with oligo-metastatic disease limited to the liver have
      been treated with single-session or hypo-fractioned radiosurgery in curative
      intent and prospectively followed until death. Follow-up (FU) was performed using
      magnetic resonance imaging (MRI) two months after radiation and at 3-month
      intervals for the first 2 years. After that annual computed tomography or MRI
      scans were performed until 5 years post-treatment. Local recurrence in the
      radiated volume and recurrence outside the treated volume were used to define
      local and distant progression. Survival times were censored at the time of the
      last FU. Results: One hundred twenty-six patients treated between 2005 and 2015
      with 194 lesions were in-cluded into this study. Median FU was 30.0 months.
      According to Response Evaluation Crite-ria in Solid Tumors, 55.2% had a complete
      remission and 11.3% a partial remission. Seventy-two point two percent recurred
      outside the radiated lesion and median overall survival was 35.2 months with a 3
      year survival rate of 47.7%. Conclusion: This is currently the largest cohort of
      stereotactic body radiation therapy treated liver lesions with a median long-term
      follow of 30 months. Robotic radiosurgery using a single session approach has a
      high efficacy to control the radiated lesion with the potential to cure patients.

PMID- 29656631
TI  - Asymptomatic Middle East Respiratory Syndrome coronavirus infection using a
      serologic survey in Korea.
AB  - OBJECTIVES: The rates of asymptomatic infection with Middle East Respiratory
      Syndrome (MERS) coronavirus vary. A serologic study was conducted to determine
      the asymptomatic MERS infection rate in healthcare workers and non-healthcare
      workers by exposure status. METHODS: Study participants were selected from
      contacts of MERS patients based on a priority system in 4 regions strongly
      affected by the 2015 MERS outbreak. A sero-epidemiological survey was performed
      in 1,610 contacts (average duration from exposure to test, 4.8 months), and the
      collected sera were tested using an enzyme-linked immunespecific assay (ELISA),
      immunofluorescence assay (IFA), and plaque reduction neutralization antibody test
      (PRNT). Among the 1,610 contacts, there were 7 ELISA-positive cases, of which 1
      exhibited positive IFA and PRNT results. RESULTS: The asymptomatic infection rate
      was 0.060% (95% confidence interval, 0.002 to 0.346). The asymptomatic MERS case
      was a patient who had been hospitalized with patient zero on the same floor of
      the hospital at the same time. The case was quarantined at home for 2 weeks after
      discharge, and had underlying diseases, including hypertension, angina, and
      degenerative arthritis. CONCLUSIONS: The asymptomatic infection was acquired via
      healthcare-associated transmission. Thus, it is necessary to extend serologic
      studies to include inpatient contacts who have no symptoms.

PMID- 29656633
TI  - Flavors of Fire: Assessing the Relative Toxicity of Smoke from Different Types of
      Wildfires.

PMID- 29656634
TI  - A Case of Bilateral External Auditory Canal Pyogenic Granuloma in a Pregnant
      Woman.
AB  - A pyogenic granuloma is one of the most common benign tumors in the head and
      neck. However, it rarely occurs in the external auditory canal (EAC). We report a
      case of a pyogenic granuloma that involved the both EAC in a pregnant woman. The
      clinical manifestation is discussed with a literature review.

PMID- 29656635
TI  - Clinical Characteristics of Dizziness Associated with Acute Peripheral Facial
      Palsy.
AB  - Background and Objectives: We aimed to assess the clinical significance of
      dizziness associated with acute peripheral facial palsy (APFP). Subjects and
      METHODS: Medical records of patients who visited an otorhinolaryngology clinic at
      a university hospital and were admitted for treatment of APFP between 2014 and
      2016 were thoroughly reviewed. RESULTS: In total, 15.3% (n=15) of patients had
      dizziness. Continuous, rotatory dizziness without exacerbating factors was most
      common and frequently accompanied by nausea/vomiting. Dizziness disappeared
      within 1 week during the hospitalization period. Patients with Ramsay Hunt
      syndrome (31.0%) had dizziness more frequently than those with Bell's palsy
      (8.7%). In addition, higher hearing thresholds and pain around the ear was
      reported more often in dizzy patients (p<0.05). Logistic regression analysis
      revealed that the initial House-Brackmann grade of facial paralysis was solely
      associated with final recovery, but dizziness was not associated with prognosis.
      Conclusions: Patients with APFP may have transient dizziness in the early stage,
      which may be more frequently accompanied by worse hearing thresholds and/or pain
      around the ear. However, these symptoms including dizziness seem to be unrelated
      to final prognosis.

PMID- 29656636
TI  - Brainstem Correlates of Comodulation Masking Release for Speech in Normal Hearing
      Adults.
AB  - Background and Objectives: Weak signals embedded in fluctuating masker can be
      perceived more efficiently than similar signals embedded in unmodulated masker.
      This release from masking is known as comodulation masking release (CMR). In this
      paper, we investigate, neural correlates of CMR in the human auditory brainstem.
      Subjects and METHODS: A total of 26 normal hearing subjects aged 18-30 years
      participated in this study. First, the impact of CMR was quantified by a
      behavioral experiment. After that, the brainstem correlates of CMR was
      investigated by the auditory brainstem response to complex sounds (cABR) in
      comodulated (CM) and unmodulated (UM) masking conditions. RESULTS: The auditory
      brainstem responses are less susceptible to degradation in response to the speech
      syllable /da/ in the CM noise masker in comparison with the UM noise masker. In
      the CM noise masker, frequency-following response (FFR) and fundamental frequency
      (F0) were correlated with better behavioral CMR. Furthermore, the subcortical
      response timing of subjects with higher CMR was less affected by the CM noise
      masker, having higher stimulus-to-noise response correlations over the FFR range.
      Conclusions: The results of the present study revealed a significant link between
      brainstem auditory processes and CMR. The findings of the present study show that
      cABR provides objective information about the neural correlates of CMR for speech
      stimulus.

PMID- 29656637
TI  - Dissecting Porosity in Molecular Crystals: Influence of Geometry, Hydrogen
      Bonding, and [pi...pi] Stacking on the Solid-State Packing of Fluorinated
      Aromatics.
AB  - Porous molecular crystals are an emerging class of porous materials that is
      unique in being built from discrete molecules rather than being polymeric in
      nature. In this study, we examined the effects of molecular structure of the
      precursors on the formation of porous solid-state structures with a series of 16
      rigid aromatics. The majority of these precursors possess pyrazole groups capable
      of hydrogen bonding, as well as electron-rich aromatics and electron-poor
      tetrafluorobenzene rings. These precursors were prepared using a combination of
      Pd- and Cu-catalyzed cross-couplings, careful manipulations of protecting groups
      on the nitrogen atoms, and solvothermal syntheses. Our study varied the geometry
      and dimensions of precursors, as well as the presence of groups capable of
      hydrogen bonding and [pi...pi] stacking. Thirteen derivatives were
      crystallographically characterized, and four of them were found to be porous with
      surface areas between 283 and 1821 m2 g-1. Common to these four porous structures
      were (a) rigid trigonal geometry, (b) [pi...pi] stacking of electron-poor
      tetrafluorobenzenes with electron-rich pyrazoles or tetrazoles, and

PMID- 29656638
TI  - Chronic Toxicity of Binary Mixtures of Six Metals (Ag, Cd, Cu, Ni, Pb, and Zn) to
      the Great Pond Snail Lymnaea stagnalis.
AB  - Although metal-mixture toxicity has recently received increasing attention, there
      is still insufficient knowledge on joint effects occurring in chronic exposures
      to relatively low metal concentrations. We characterized the chronic toxicity of
      binary mixtures of six metals (Ag, Cd, Cu, Ni, Pb, and Zn) in 14 day growth tests
      with juveniles of the metal-sensitive freshwater snail Lymnaea stagnalis.
      Observations were compared with predictions from individual metals and from the
      two most frequently used mixture models: concentration addition (CA) and
      independent action (IA). Predictions based on measured total dissolved
      concentrations and on calculated free-ion activities did not differ greatly
      because multimetal geochemical interactions in the tests were limited. In around
      half of the tests, mixture toxicity was higher than the greatest effect caused by
      the individual metals, arguing in favor of considering joint effects. When the
      additive models were used, the great majority of interactions were either
      additive or less than additive (i.e., antagonism). In general, the IA model was
      the most accurate, while the CA model was the most conservative. Along with other
      studies, these findings suggest that, at least for binary combinations, the
      simple CA model may provide satisfactory protection from the chronic metal
      toxicity of metal mixtures to aquatic organisms.

PMID- 29656639
TI  - Mitigating the Expansion of Harmful Algal Blooms Across the Freshwater-to-Marine
      Continuum.
AB  - Anthropogenic nutrient overenrichment, coupled with rising temperatures, and an
      increasing frequency of extreme hydrologic events (storms and droughts) are
      accelerating eutrophication and promoting the expansion of harmful algal blooms
      (HABs) across the freshwater-to-marine continuum. All HABs-with a focus here on
      cyanobacterial blooms-pose serious consequences for water supplies, fisheries,
      recreational uses, tourism, and property values. As nutrient loads grow in
      watersheds, they begin to compound the effects of legacy stores. This has led to
      a paradigm shift in our understanding of how nutrients control eutrophication and
      blooms. Phosphorus (P) reductions have been traditionally prescribed exclusively
      for freshwater systems, while nitrogen (N) reductions were mainly stressed for
      brackish and coastal waters. However, because most systems are hydrologically
      interconnected, single nutrient (e.g., P only) reductions upstream may not
      necessarily reduce HAB impacts downstream. Reducing both N and P inputs is the
      only viable nutrient management solution for long-term control of HABs along the
      continuum. This article highlights where paired physical, chemical, or biological
      controls may improve beneficial uses in the short term, and offers management
      strategies that should be enacted across watershed scales to combat the global
      expansion of HABs across geographically broad freshwater-to-marine continua.

PMID- 29656640
TI  - Phase Equilibria of Polydisperse Square-Well Chain Fluid Confined in Random
      Porous Media: TPT of Wertheim and Scaled Particle Theory.
AB  - Extension of Wertheim's thermodynamic perturbation theory and its combination
      with scaled particle theory is proposed and applied to study the liquid-gas phase
      behavior of polydisperse hard-sphere square-well chain fluid confined in the
      random porous media. Thermodynamic properties of the reference system,
      represented by the hard-sphere square-well fluid in the matrix, are calculated
      using corresponding extension of the second-order Barker-Henderson perturbation
      theory. We study effects of polydispersity and confinement on the phase behavior
      of the system. While polydispersity causes increase of the region of phase
      coexistence due to the critical temperature increase, confinement decreases the
      values of both critical temperature and critical density making the region of
      phase coexistence smaller. This effect is enhanced with the increase of the size
      ratio of the fluid and matrix particles. The increase of the average chain length
      at fixed values of polydispersity and matrix density shifts the critical point to
      a higher temperature and a slightly lower density.

PMID- 29656641
TI  - Attachment of Alcanivorax borkumensis to Hexadecane-In-Artificial Sea Water
      Emulsion Droplets.
AB  - Alcanivorax borkumensis (AB) is a marine bacterium that dominates bacterial
      communities around many oil spills because it enzymatically degrades the oil
      while using it as a nutrient source. Several dispersants have been used to
      produce oil-in-water emulsions following a spill. Compared to surface slicks, the
      additional oil-water surface area produced by emulsification provides greater
      access to the oil and accelerates its degradation. We deliberately cultured AB
      cells using hexadecane as the only nutrient source. We then examined the first
      critical step of the biodegradation process, the attachment of these AB cells to
      hexadecane-water interfaces, using fluorescence microscopy and cryogenic scanning
      electron microscopy. The hexadecane-in-artificial sea water (ASW) emulsions were
      produced by gentle shaking and were stabilized either by AB alone, by Corexit
      9500, by Tween 20, or by carbon black particles. When no dispersants were used,
      AB stabilizes the emulsion, and bacterial cells attach to the hexadecane droplets
      within the first 3 days. When Corexit 9500 was used as the dispersant, AB did not
      attach to the hexadecane droplets over 3 days, and many AB cells in the aqueous
      phase appeared dead. Only limited attachment was observed after 7 days. No AB
      attachment was observed over 3 days when Tween 20 was used as the dispersant.
      However, the bacteria used Tween 20 in the ASW as a nutrient. Large amounts of AB
      attached to carbon black stabilized hexadecane droplets within 3 days. An
      analysis that accounts for van der Waals and electrostatic interactions is unable
      to predict all of these observations, indicating that the attachment of AB to the
      hexadecane is a complex phenomenon that goes beyond simple physiochemical
      effects. While these experiments do not mimic conditions in the open ocean where
      the large amount of water dilutes any emulsion stabilizer, they provide important
      insights on bacteria adhesion to oil, a critical step in the oil degradation
      process following a marine spill.

PMID- 29656642
TI  - (Semi)ladder-Type Bithiophene Imide-Based All-Acceptor Semiconductors: Synthesis,
      Structure-Property Correlations, and Unipolar n-Type Transistor Performance.
AB  - Development of high-performance unipolar n-type organic semiconductors still
      remains as a great challenge. In this work, all-acceptor bithiophene imide-based
      ladder-type small molecules BTI n and semiladder-type homopolymers PBTI n ( n = 1
      5) were synthesized, and their structure-property correlations were studied in
      depth. It was found that Pd-catalyzed Stille coupling is superior to Ni-mediated
      Yamamoto coupling to produce polymers with higher molecular weight and improved
      polymer quality, thus leading to greatly increased electron mobility (MUe). Due
      to their all-acceptor backbone, these polymers all exhibit unipolar n-type
      transport in organic thin-film transistors, accompanied by low off-currents (10
      10-10-9 A), large on/off current ratios (106), and small threshold voltages (~15
      25 V). The highest MUe, up to 3.71 cm2 V-1 s-1, is attained from PBTI1 with the
      shortest monomer unit. As the monomer size is extended, the MUe drops by 2 orders
      to 0.014 cm2 V-1 s-1 for PBTI5. This monotonic decrease of MUe was also observed
      in their homologous BTI n small molecules. This trend of mobility decrease is in
      good agreement with the evolvement of disordered phases within the film, as
      revealed by Raman spectroscopy and X-ray diffraction measurements. The extension
      of the ladder-type building blocks appears to have a large impact on the motion
      freedom of the building blocks and the polymer chains during film formation, thus
      negatively affecting film morphology and charge carrier mobility. The result
      indicates that synthesizing building blocks with more extended ladder-type
      backbone does not necessarily lead to improved mobilities. This study marks a
      significant advance in the performance of all-acceptor-type polymers as unipolar
      electron transporting materials and provides useful guidelines for further
      development of (semi)ladder-type molecular and polymeric semiconductors for
      applications in organic electronics.

PMID- 29656643
TI  - Direct Experimental Characterization of Glycosyl Cations by Infrared Ion
      Spectroscopy.
AB  - Glycosyl cations are crucial intermediates formed during enzymatic and chemical
      glycosylation. The intrinsic high reactivity and short lifetime of these reaction
      intermediates make them very challenging to characterize using spectroscopic
      techniques. Herein, we report the use of collision induced dissociation tandem
      mass spectrometry to generate glycosyl cations in the gas phase followed by
      infrared ion spectroscopy using the FELIX infrared free electron laser. The
      experimentally observed IR spectra were compared to DFT calculated spectra
      enabling the detailed structural elucidation of elusive glycosyl oxocarbenium and
      dioxolenium ions.

PMID- 29656644
TI  - Tuna Oil Alleviates d-Galactose Induced Aging in Mice Accompanied by Modulating
      Gut Microbiota and Brain Protein Expression.
AB  - To discern whether tuna oil modulates the expression of brain proteins and the
      gut microbiota structure during aging induced by d-galactose, we generated an
      aging mouse model with d-galactose treatment, and the mice showed aging and
      memory deterioration symptoms according to physiological and biochemical indices.
      Treatment with different doses of tuna oil alleviated the symptoms; the high dose
      showed a better effect. Subsequently, brain proteomic analysis showed the
      differentially expressed proteins were involved in damaged synaptic system
      repairment and signal transduction system enhancement. In addition, tuna oil
      treatment restored the diversity of gut microbiota, 27 key operational taxonomic
      units, which were identified using a redundancy analysis and were significantly
      correlated with at least one physiological index and three proteins or genes.
      These findings suggest that the combination of proteomics and gut microbiota is
      an effective strategy to gain novel insights regarding the effect of tuna oil
      treatment on the microbiota-gut-brain axis.

PMID- 29656645
TI  - Plant Uptake and Metabolism of 2,4-Dibromophenol in Carrot: In Vitro Enzymatic
      Direct Conjugation.
AB  - Plants can extensively uptake organic contaminants from soil and subsequently
      transform them into various products. Those compounds containing hydroxyl may
      undergo direct conjugation with endogenous biomolecules in plants, and
      potentially be preserved as conjugates, thus enabling overlooked risk via
      consumptions of food crops. In this study, we evaluated the uptake and metabolism
      of 2,4-dibromophenol (DBP) by both carrot cells and whole plant. DBP was
      completely removed from cell cultures with a half-life of 10.8 h. Four saccharide
      conjugates, three amino acid conjugates, and one phase I metabolite were
      identified via ultraperformance liquid chromatography quadrupole time-of-flight
      mass spectrometry analysis. The dibromophenol glucopyranoside (glucose conjugate)
      was quantitated by synthesized standard and accounted for 9.3% of the initial
      spiked DBP at the end of incubation. The activity of glycosyltransferase was
      positively related to the production of 2,4-dibromophenol glucopyranoside ( p =
      0.02, R2 = 0.86), implying the role of enzymatic catalysis involved in phase II
      metabolism.

PMID- 29656646
TI  - Toward a New Brewing Control Chart for the 21st Century.
AB  - This paper describes new results from a base model of brewing from a bed of
      packed coffee grains. The model solves for the diffusion of soluble species out
      of a distribution of particles into the flow through the bed pore space. It
      requires a limited set of input parameters. It gives a simple picture of the
      basic physics of coffee brewing and sets out a set of reduced variables for this
      process. The importance of bed extraction efficiency is elucidated. A coffee
      brewing control chart has been widely used to describe the region of ideal coffee
      brewing for some 50 years. A new chart is needed, however, one that connects
      actual brewing conditions (weight, flow rate, brew time, grind, etc.) to the
      yield and strength of brews. The paper shows a new approach to brewing control
      charts, including brew time and bed extraction efficiency as control parameters.
      Using the base model, an example chart will be given for a particular grind ratio
      of coarse to fine particles, and an "espresso regime" will be picked out. From
      such a chart yield, volume and strength of a brew can be read off at will.

PMID- 29656647
TI  - Tea Polysaccharides Inhibit Colitis-Associated Colorectal Cancer via Interleukin
      6/STAT3 Pathway.
AB  - The interleukin-6 (IL-6)/signal transducer and activator of transcription (STAT)
      3 signaling pathway regulates proliferation and survival of intestinal epithelial
      cells and has profound impact on the tumorigenesis of colitis-associated cancer
      (CAC). Tea polysaccharides (TPS) are the major nutraceutical component isolated
      from tea-leaves and are known to possess antioxidant, anti-inflammatory, and
      antitumor bioactivities. Here, we investigated the antitumor activities of TPS on
      CAC using the azoxymethane/dextran sulfate sodium (AOM/DSS) mouse model and IL-6
      induced colorectal cancer cell line (CT26) and determined whether TPS exerted its
      antitumor effects through the IL-6/STAT3 pathway. Results demonstrated that TPS
      significantly decreased the tumor incidence, tumor size, and markedly inhibited
      the infiltration of pro-inflammatory cells and the secretion of pro-inflammatory
      cytokines via balancing cellular microenvironment. Furthermore, we found that TPS
      suppressed the activation of STAT3 and transcriptionally regulated the
      expressions of downstream genes including MMP2, cyclin Dl, survivin, and VEGF
      both in vivo and in vitro. Thus, it was concluded that TPS attenuated the
      progress of CAC via suppressing IL-6/STAT3 pathway and downstream genes'
      expressions, which indicated that TPS may be a hopeful antitumor agent for the
      prevention and treatment of colon cancer.

PMID- 29656648
TI  - Germinated Brown Rice Attenuates Atherosclerosis and Vascular Inflammation in Low
      Density Lipoprotein Receptor-Knockout Mice.
AB  - The present study investigates the impact of germinated brown rice (GBR) on
      atherosclerosis and the underlying mechanism in low-density lipoprotein receptor
      knockout (LDLr-KO) mice. The intensity of atherosclerosis in aortas of LDLr-KO
      mice receiving diet supplemented with 60% GBR (weight/weight) was significantly
      less than that in mice fed with 60% white rice (WR) or control diet ( p < 0.05);
      all diets contained 0.06% cholesterol. WR or GBR diet did not significantly alter
      plasma total or LDL-cholesterol, fecal sterols, or glucose, or the activities of
      antioxidant enzymes, compared to the control diet. The adhesion of monocytes to
      aortas from LDLr-KO mice fed with WR diet was significantly more than that from
      mice receiving the control diet ( p < 0.01). GBR diet decreased monocyte adhesion
      to aortas compared to WR diet ( p < 0.01). GBR diet also reduced the levels of
      plasminogen activator inhibitor-1 (PAI-1), monocyte chemotactic protein-1 (MCP
      1), and tumor necrosis factor-alpha (TNF-alpha) in plasma, and the abundances of
      MCP-1, PAI-1, TNF-alpha, intracellular cell adhesion molecule-1, toll-like
      receptor-4, PAI-1, LDLr-like protein, and urokinase plasminogen activator and its
      receptor in aortas or hearts from LDLr-KO mice in comparison to the WR diet ( p <
      0.05, 0.01, respectively). The findings suggest that GBR administration
      attenuated atherosclerosis and vascular inflammation in LDLr-KO mice compared to
      WR. The anti-atherosclerotic effect of GBR in LDLr-KO mice at least in part
      results from its anti-inflammatory activity.

PMID- 29656649
TI  - Wetting Behavior of Metal-Catalyzed Chemical Vapor Deposition-Grown One
      Dimensional Cubic-SiC Nanostructures.
AB  - Superhydrophobic surfaces can be fabricated by using the self-assembled
      nanoarchitecture of 3C-SiC one-dimensional (1D) nanostructures as they are
      capable of forming a dense network of micro-nano air pockets without any help
      from external sources. Herein, the metal-catalyzed growth of 3C-SiC
      nanowires/nanorods on Si substrates via vapor-liquid-solid mechanism using five
      different catalysts, that is, chemically synthesized Au nanoparticles and direct
      current-sputtered thin films of Au, Cu, Ni, and Ti, is reported. Relatively new
      or unexplored catalysts such as thin films of Cu and Ti, as well as drop-cast Au
      nanoparticles, were used. An optimized and separate growth was carried out for
      each catalyst in an inductively heated horizontal cold-wall atmospheric pressure
      chemical vapor deposition reactor. An insight into the catalytic growth mechanism
      of 3C-SiC 1D nanostructures has been presented. All of the bare samples exhibited
      superhydrophilic behavior, whereas hierarchical Au/Pd nanostructure-coated 3C-SiC
      nanorod samples grown using Au and Ni thin-film catalysts exhibited hydrophobic
      and superhydrophobic behavior, respectively. As the better results were obtained
      for Ni thin-film catalysts in terms of growth density and high water contact
      angle (WCA ~ 160 degrees ), therefore, the growth temperature, as well as the
      growth time-dependent wetting behavior, was also studied. It was found that the
      WCA increased as the growth time and temperature increased because of the
      increase in the growth density, and it finally reached to an optimum value at the
      growth temperature of 1200  degrees C and the growth time of 1 h. Furthermore,
      their wetting behavior was studied by using a variety of high surface tension
      (water, milk, tea, and glycerin) and low surface tension (organic liquids such as
      n-hexane, ethanol, etc.) liquids. High surface tension liquids exhibited
      superhydrophobic behavior, whereas low surface tension liquids exhibited
      superhydrophilic behavior. Hence, these fabricated nanostructured surfaces can be
      exploited for oil-water separation, electrowetting, water harvesting, self
      cleaning, lab on a chip, and micro-/nanofluidic device applications.

PMID- 29656650
TI  - Discovery of Tetrahydroquinoxalines as Bromodomain and Extra-Terminal Domain
      (BET) Inhibitors with Selectivity for the Second Bromodomain.
AB  - The bromodomain and extra-terminal domain (BET) family of proteins bind
      acetylated lysine residues on histone proteins. The four BET bromodomains-BRD2,
      BRD3, BRD4, and BRDT-each contain two bromodomain modules. BET bromodomain
      inhibition is a potential therapy for various cancers and immunoinflammatory
      diseases, but few reported inhibitors show selectivity within the BET family.
      Inhibitors with selectivity for the first or second bromodomain are desired to
      aid investigation of the biological function of these domains. Focused library
      screening identified a series of tetrahydroquinoxalines with selectivity for the
      second bromodomains of the BET family (BD2). Structure-guided optimization of the
      template improved potency, selectivity, and physicochemical properties,
      culminating in potent BET inhibitors with BD2 selectivity.

PMID- 29656651
TI  - TiO2 Photocatalysis in Aromatic "Redox Tag"-Guided Intermolecular Formal [2 + 2]
      Cycloadditions.
AB  - Since the pioneering work by Macmillan, Yoon, and Stephenson, homogeneous
      photoredox catalysis has occupied a central place in new reaction development in
      the field of organic chemistry. While heterogeneous semiconductor photocatalysis
      has also been studied extensively, it has generally been recognized as a redox
      option in inorganic chemistry where such "photocatalysis" is most often used to
      catalyze carbon-carbon bond cleavage and not in organic chemistry where bond
      formation is usually the focal point. Herein, we demonstrate that titanium
      dioxide photocatalysis is a powerful redox option to construct carbon-carbon
      bonds by using intermolecular formal [2 + 2] cycloadditions as models. Synergy
      between excited electrons and holes generated upon irradiation is expected to
      promote the overall net redox neutral process. Key for the successful application
      is the use of a lithium perchlorate/nitromethane electrolyte solution, which
      exhibits remarkable Lewis acidity to facilitate the reactions of carbon-centered
      radical cations with carbon nucleophiles. The reaction mechanism is reasonably
      understood based on both intermolecular and intramolecular single electron
      transfer regulated by an aromatic "redox tag". Most of the reactions were
      completed in less than 30 min even in aqueous and/or aerobic conditions without
      the need for sacrificial reducing or oxidizing substrates generally required for
      homogeneous photoredox catalysis.

PMID- 29656652
TI  - Oral health disparities among adolescents from urban and rural communities of
      central Chile.
AB  - PURPOSE: Rural populations may be at increased risk for prevalent oral diseases.
      The aim of this study was to compare oral health status of adolescents of rural
      and urban areas from central Chile. METHODS: A representative sample of 552 and
      486 adolescents aged 12 and 15 years, respectively, was examined using WHO
      methods. Adolescents were chosen from schools belonging to urban and rural
      districts of the region. Caries status was obtained by decayed, missing, filled
      teeth (DMFT) and significant caries (SiC) indexes. The gingival exam included the
      oral hygiene index (OHI) of Silness and L&ouml;e and the gingival index (GI) of
      L&ouml;e and Silness. Clinical attachment loss and community periodontal index
      (CPI) were restricted to 15-year-old adolescents. Statistical comparisons of
      medians and means were performed with the Mann-Whitney U-test. To determine the
      association between caries experience and oral hygiene and gingival indexes,
      Spearman&#39;s correlation was used at p<0.05. RESULTS: Twelve-year-old children
      from rural areas had caries prevalence of 67.50%, which was significantly higher
      (p<0.05) than children from urban areas, who had 54.04%. Caries experience of 12
      year-old rural children was significantly higher (DMFT 3.36; standard deviation
      (SD) 2.71) than that of urban children (DMFT 2.29; SD 2.17) (p=0.0001). Rural
      adolescents also showed increased caries severity (SiC 6.21; SD 2.44), whereas
      urban children showed had a SiC of 4.71 (SD 1.74) (p=0.0001). For periodontal
      indexes, the average GI for 12-year-olds was 1.51 (SD 0.33), which corresponds to
      moderate inflammation, but rural subjects (GI 1.55; SD 0.34) had higher values
      (p=0.002) than their urban counterparts (GI 1.45; SD 0.29). In 15-year-old
      adolescents, caries prevalence was significantly higher in rural (73.58%) than in
      urban (64.59%) individuals (p<0.05). Although not significant, caries experience
      for 15-year-olds in rural areas, like in the other age group, was slightly higher
      than for urban 15-year-olds (DMFT 5.03; SD 3.61 and DMFT 4.65; SD 3.58,
      respectively) (p=0.238). The SiC in the rural subjects (9.16; SD 2.26) of this
      age group was significantly higher than for urban adolescents (8.51; SD 3.00). No
      significant differences either in the OHI (p=0.418) or in the GI (p=0.624) were
      observed between rural and urban participants. CONCLUSIONS: Adolescents of
      central Chile show clear disparities in oral health, with rural communities more
      affected. Gingival health seems to be less impacted by rurality than caries
      experience. Other social determinants of oral health may also explain these
      results, and further research appears necessary.

PMID- 29656653
TI  - Derivatization, molecular docking and in vitro acetylcholinesterase inhibitory
      activity of glycyrrhizin as a selective anti-Alzheimer agent.
AB  - Acetylcholinesterase inhibitors (AChE-Is) increase both level and duration of
      action of acetylcholine (ACh); thus, alleviate symptoms of Alzheimer's disease
      (AD). Glycyrrhizin, is the main active compound in liquorice root. Its aglycone,
      glycyrrhetinic acid, has shown several beneficial pharmacological activities.
      This study reports the synthesis and screening of a series of glycyrrhetinic acid
      analogs as AChE-Is. Fourteen derivatives were prepared, of which five derivatives
      are recorded as new viz., 3-phenyl-carbamoyl-18beta-glycyrrhetinic acid (J9), 3
      acetyl-18beta-glycyrrhetinic-30-anilinamide (J10), 3-acetyl-18beta-glycyrrhetinic
      30-ethanolamide (J11), 3-acetyl-18beta-glycyrrhetinic-30-n-butylamide (J12) and
      18beta-glycyrrhetinic acid-30-prenyl ester (J14), in addition to nine known
      derivatives (J1-J8 & J13). Compounds J12, J11, J0 and J3 showed remarkable AChE-I
      activity with IC50 values of 3.43, 5.39, 6.27 and 8.68 MUM, respectively. These
      results are in full agreement with the docking study. The active compounds were
      non-cytotoxic to normal cells (WI-38).

PMID- 29656654
TI  - A new galloyl glycoside from Lotus corniculatus.
AB  - A new galloyl glucoside, 2,6-di-O-acetyl 1-O-galloyl beta-D-glucose (1), along
      with five known phenolic compounds were isolated from the whole plants of Lotus
      corniculatus. Their structures were elucidated by means of extensive
      spectroscopic analysis. Compound 1 was assessed for its cytotoxicity against five
      human tumour lines (HL-60, SMMC-7721, A-549, MCF-7 and SW-480), and the result
      showed that it had no activity.

PMID- 29656655
TI  - Mean Platelet Volume, Neutrophil-Lymphocyte Ratio, and Long-Term Major
      Cardiovascular Events.

PMID- 29656656
TI  - Effect of Coronary Collaterals on Prognosis in Patients Undergoing Primary
      Percutaneous Coronary Intervention for Acute ST-Segment Elevation Myocardial
      Infarction: A Meta-Analysis.
AB  - The impact of coronary collaterals on the prognosis in patients with acute ST
      segment elevation myocardial infarction (STEMI) in the era of coronary
      revascularization remains controversial. The purpose of this meta-analysis was to
      investigate the effect of coronary collateral on clinical outcomes, especially
      mortality (>=6 months), in patients undergoing primary percutaneous coronary
      intervention (PCI) for STEMI. Eligible observational studies were selected by
      searching PubMed, EMBASE, and Cochrane Library up to August 9, 2017. Overall, 14
      observational studies involving 10 411 patients were included. Coronary
      collaterals were found to reduce the risk of long-term mortality (>=6 months;
      risk ratio [RR]: 0.65, 95% confidence interval [CI]: 0.55-0.76) as well as in
      hospital plus 30-day mortality (RR: 0.61, 95% CI: 0.47-0.78) in patients
      undergoing PCI for STEMI. In addition, pooling the risk-adjusted or propensity
      matched data showed a significant reduction in long-term mortality (RR: 0.68, 95%
      CI: 0.49-0.95) and in-hospital plus 30-day mortality (RR: 0.27, 95% CI: 0.13
      0.55) in patients with collateral circulation. However, no significant difference
      was found in the risk of recurrent myocardial infarction and target vessel
      revascularization between the 2 groups. Therefore, it was found that coronary
      collaterals have a beneficial effect on long-term survival (>=6 months) as well
      as in-hospital plus 30-day survival in patients undergoing primary PCI for STEMI.

PMID- 29656657
TI  - Phytochemical profile and biological activities of Deverra tortuosa (Desf.)DC.: a
      desert aromatic shrub widespread in Northern Region of Saudi Arabia.
AB  - The present study describes the chemical composition of the essential oil of
      different plant parts of Devrra tortuosa; in vivo and in vitro biological
      activities of plant extract and essential oils. Apiol was found to be the major
      component of the oil (between 65.73% and 74.41%). The best antioxidant activities
      were observed for the oil of flowers (IC50 = 175 MUg/ml). The samples of stems
      and roots exhibit lower antioxidant activity (IC50 = 201 MUg/ml and 182 MUg/ml,
      respectively). The values of IC50 showed that the extracts of methanol exhibit
      the highest antioxidants activities (IC50 = 64.8 102 MUg/ml). EOs showed
      excellent antifungal activity against yeasts with low azole susceptibilities
      (i.e. Malassezia spp. and Candida krusei). The MIC values of oils varied between
      2.85 mg/mL and 27 mg/mL. The obtained results also showed that the plant extracts
      inhibited the germination and the shoot and root growth of Triticum aestivum
      seedlings.

PMID- 29656658
TI  - Primary angiitis of the central nervous system mimicking a cerebellar tumor.
AB  - Primary angiitis of the central nervous system (PACNS), is a rare and poorly
      understood disease mainly characterized by multifocal segmental inflammation of
      the small and medium vessels of the central nervous system. Most PACNS are
      multiple lesions, occurring in the supratentorial subcortical and deep white
      matter, and only a few cases present as a tumor-like mass lesion. Herein, we
      describe an extremely rare case of PACNS occurred in the cerebellum, which
      mimicked a cerebellar tumor. To the best of our knowledge, this is the first
      reported case of cerebellar tumor-like PACNS proved by histopathological
      examination.

PMID- 29656659
TI  - Optimization of spray drying conditions to microencapsulate cupuassu (Theobroma
      grandiflorum) seed by-product extract.
AB  - Cupuassu (Theobroma grandiflorum Schum.) is a popular Amazonian fruit because of
      its intense aroma and nutritional value, whose lipid fraction is alternatively
      used in cosmetics. To preserve active principles and ensure their controlled
      release, extract was microencapsulated by spray drying. Influence of spray-drying
      conditions on microencapsulation of cupuassu seed by-product extract was
      investigated according to a 33-Box Behnken factorial design, selecting inlet
      temperature, maltodextrin concentration and feed flowrate as independent
      variables, and total polyphenol and flavonoid contents, antiradical power, yields
      of drying and microencapsulation as responses. Fitting the results by second
      order equations and modelling by Response Surface Methodology allowed predicting
      optimum conditions. Epicatechin and glycosylated quercetin were the major
      microencapsulated flavonoids. Microparticles showed satisfactory antiradical
      power and stability at 5  degrees C or under simulated gastrointestinal
      conditions, thus they may be used to formulate new foods or pharmaceuticals.

PMID- 29656660
TI  - Cytotoxic flavonoids from two Lonchocarpus species.
AB  - A new isoflavone, 4'-prenyloxyvigvexin A (1) and a new pterocarpan, (6aR,11aR)
      3,8-dimethoxybitucarpin B (2) were isolated from the leaves of Lonchocarpus
      bussei and the stem bark of Lonchocarpus eriocalyx, respectively. The extract of
      L. bussei also gave four known isoflavones, maximaisoflavone H, 7,2'-dimethoxy
      3',4'-methylenedioxyisoflavone, 6,7,3'-trimethoxy-4',5'-methylenedioxyisoflavone,
      durmillone; a chalcone, 4-hydroxylonchocarpin; a geranylated phenylpropanol,
      colenemol; and two known pterocarpans, (6aR,11aR)-maackiain and (6aR,11aR)
      edunol. (6aR,11aR)-Edunol was also isolated from the stem bark of L. eriocalyx.
      The structures of the isolated compounds were elucidated by spectroscopy. The
      cytotoxicity of the compounds was tested by resazurin assay using drug-sensitive
      and multidrug-resistant cancer cell lines. Significant antiproliferative effects
      with IC50 values below 10 MUM were observed for the isoflavones 6,7,3'-trimethoxy
      4',5'-methylenedioxyisoflavone and durmillone against leukemia CCRF-CEM cells;
      for the chalcone, 4-hydroxylonchocarpin and durmillone against its resistant
      counterpart CEM/ADR5000 cells; as well as for durmillone against the resistant
      breast adenocarcinoma MDA-MB231/BCRP cells and resistant gliobastoma
      U87MG.DeltaEGFR cells.

PMID- 29656661
TI  - High Oct4 predicted worse prognosis of right-sided colon cancer patients.
AB  - AIM: This present study was aimed to compare the role of Oct4 in left-sided colon
      cancer (LCC) with right-sided colon cancer (RCC). PATIENTS & METHODS: One hundred
      and fifty one pathology specimens, 68 frozen-thawed tumors and cell lines were
      used to evaluate the role of Oct4 in LCC and RCC through immunohistochemistry,
      western blot and real-time quantitative PCR. RESULTS: In LCC, positive expression
      of Oct4 was positively related to differentiation and Dukes stage (p < 0.01).
      Only in RCC, Oct4 expression was also positively related to lymphatic invasion
      and survival rates of 'negative group' were significantly higher. CONCLUSION: In
      summary, Oct4 was related to tumor differentiation and later Dukes stage in colon
      cancer, and was correlated with invasion of lymphatic only in RCC. In addition,
      Oct4 was a potential prognostic indicator in RCC.

PMID- 29656662
TI  - Beneficial effects of Salvia miltiorrhiza in the healing of burn wounds: an
      experimental study in rats.
AB  - INTRODUCTION: Burn healing is a complicated process and very few treatments can
      positively alter its effects. The aim of this study was to investigate the
      effects Salvia miltiorrhiza (SM -Danshen), a traditional Chinese medicine, on
      burn wound healing. MATERIAL AND METHODS: Twenty rats were included in this study
      and divided into two groups. 3 * 2 cm wide burn areas were created in the dorsal
      skin of all the animals with thermal contact. Intraoral 1 ml/day saline and 1
      g/kg/day SM were given in control and experiment groups, respectively. Fourteen
      days following the burn injury burn zones were evaluated with indocyanine green
      SPY imaging device, and multiple samples were collected for histopathological
      evaluation. Standard photographs were taken for the evaluation of necrotic skin
      areas. RESULTS: Neovascularization was increased in the SM group when compared
      with the control group (p = 0.0406). SPY studies revealed a meaningful increase
      in the tissue perfusion in the SM group (p = 0.0286). The average amount of
      necrotic area in the control and experiment group on the postoperative 14th day
      was 71.6% (+/-16.51) and 42.5% (+/-10.64) respectively (p = 0.0002). CONCLUSION:
      Our study shows that SM can decrease the amount of necrosis in burn wounds by
      increasing tissue perfusion and neovascularization.

PMID- 29656663
TI  - Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms
      of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results
      of a Double-Blind, Randomized, Placebo-Controlled Study.
AB  - OBJECTIVE: The authors compared the efficacy of standard-of-care treatment plus
      intranasal esketamine or placebo for rapid reduction of symptoms of major
      depression, including suicidality, among individuals at imminent suicide risk.
      METHOD: In a double-blind, multicenter, proof-of-concept study, 68 participants
      were randomly assigned to receive esketamine (84 mg) or placebo twice weekly for
      4 weeks, in addition to comprehensive standard-of-care treatment. The primary
      efficacy endpoint was change in score from baseline to 4 hours after initial dose
      on the Montgomery-Asberg Depression Rating Scale (MADRS). Clinician global
      judgment of suicide risk (from the Suicide Ideation and Behavior Assessment Tool)
      was also assessed. Secondary endpoints included these measures at 24 hours and
      double-blind endpoint at day 25. RESULTS: A significantly greater improvement in
      MADRS score was observed in the esketamine group compared with the placebo group
      at 4 hours (least-square mean difference=-5.3, SE=2.10; effect size=0.61) and at
      ~24 hours (least-square mean difference=-7.2, SE=2.85; effect size=0.65), but not
      at day 25 (least-square mean difference=-4.5, SE=3.14; effect size=0.35).
      Significantly greater improvement was also observed in the esketamine group on
      the MADRS suicidal thoughts item score at 4 hours (effect size=0.67), but not at
      24 hours (effect size=0.35) or at day 25 (effect size=0.29). Between-group
      reductions in clinician global judgment of suicide risk scores were not
      statistically different at any time point. The most common adverse events among
      participants in the esketamine group were nausea, dizziness, dissociation,
      unpleasant taste, and headache. CONCLUSIONS: These preliminary findings indicate
      that intranasal esketamine compared with placebo, given in addition to
      comprehensive standard-of-care treatment, may result in significantly rapid
      improvement in depressive symptoms, including some measures of suicidal ideation,
      among depressed patients at imminent risk for suicide.

PMID- 29656664
TI  - Epigenetic Aging in Major Depressive Disorder.
AB  - OBJECTIVE: Major depressive disorder is associated with an increased risk of
      mortality and aging-related diseases. The authors examined whether major
      depression is associated with higher epigenetic aging in blood as measured by DNA
      methylation (DNAm) patterns, whether clinical characteristics of major depression
      have a further impact on these patterns, and whether the findings replicate in
      brain tissue. METHOD: DNAm age was estimated using all methylation sites in blood
      of 811 depressed patients and 319 control subjects with no lifetime psychiatric
      disorders and low depressive symptoms from the Netherlands Study of Depression
      and Anxiety. The residuals of the DNAm age estimates regressed on chronological
      age were calculated to indicate epigenetic aging. Major depression diagnosis and
      clinical characteristics were assessed with questionnaires and psychiatric
      interviews. Analyses were adjusted for sociodemographic characteristics,
      lifestyle, and health status. Postmortem brain samples of 74 depressed patients
      and 64 control subjects were used for replication. Pathway enrichment analysis
      was conducted using ConsensusPathDB to gain insight into the biological processes
      underlying epigenetic aging in blood and brain. RESULTS: Significantly higher
      epigenetic aging was observed in patients with major depression compared with
      control subjects (Cohen's d=0.18), with a significant dose effect with increasing
      symptom severity in the overall sample. In the depression group, epigenetic aging
      was positively and significantly associated with childhood trauma score. The case
      control difference was replicated in an independent data set of postmortem brain
      samples. The top significantly enriched Gene Ontology terms included neuronal
      processes. CONCLUSIONS: As compared with control subjects, patients with major
      depression exhibited higher epigenetic aging in blood and brain tissue,
      suggesting that they are biologically older than their corresponding
      chronological age. This effect was even more profound in the presence of
      childhood trauma.

PMID- 29656665
TI  - Prevalence and Correlates of Prescription Stimulant Use, Misuse, Use Disorders,
      and Motivations for Misuse Among Adults in the United States.
AB  - OBJECTIVE: The authors sought to simultaneously examine the prevalence and
      correlates of prescription stimulant use, misuse, use disorders, and motivations
      for misuse in the U.S. adult population. METHOD: This was a nationally
      representative household population study of adults age 18 or older from the 2015
      and 2016 National Surveys on Drug Use and Health (N=102,000). Measurements
      included prescription stimulant use, use without misuse, misuse without use
      disorders, and misuse with use disorders, as well as sociodemographic
      characteristics, health conditions, and mental health factors. RESULTS: Among
      U.S. adults, 6.6% (annual average) used prescription stimulants overall; 4.5%
      used without misuse, 1.9% misused without use disorders, and 0.2% had use
      disorders. Adults with past-year prescription stimulant use disorders did not
      differ from those with misuse without use disorders in any of the examined
      sociodemographic characteristics and in many of the examined substance use
      problems. The most commonly reported motivations for misuse were to help be alert
      or concentrate (56.3%). The most likely source of misused prescription stimulants
      was by obtaining them free from friends or relatives (56.9%). More frequent
      prescription stimulant misuse and use disorder were associated with an increased
      likelihood of obtaining medications from physicians or from drug dealers or
      strangers and less likelihood of obtaining them from friends or relatives.
      CONCLUSIONS: Approximately 16.0 million U.S. adults used prescription stimulants
      in the preceding year (annual average), 5.0 million misused prescription
      stimulants, and 0.4 million had use disorders. Cognitive enhancement was the most
      commonly reported reason for misusing prescription stimulants. Patients who are
      using their medication for cognitive enhancement or diverting their medication to
      others present a high risk.

PMID- 29656666
TI  - Can a Framework Be Established for the Safe Use of Ketamine?

PMID- 29656667
TI  - Haemodialysis at home: review of current dialysis machines.
AB  - INTRODUCTION: Only a minority of patients with chronic kidney disease treated by
      hemodialysis are currently treated at home. Until relatively recently, the only
      type of hemodialysis machine available for these patients was a slightly smaller
      version of the standard machines used for in-center dialysis treatments. Areas
      covered: There are now an alternative generation of dialysis machines
      specifically designed for home hemodialysis. The home dialysis patient wants a
      smaller machine, which is intuitive to use, easy to trouble shoot, robust and
      reliable, quick to setup and put away, requiring minimal waste disposal. The
      machines designed for home dialysis have some similarities in terms of touch
      screen patient interfaces, and using pre-prepared cartridges to speed up setting
      up the machine. On the other hand, they differ in terms of whether they use
      slower or standard dialysate flows, prepare batches of dialysis fluid, require
      separate water purification equipment, or whether this is integrated, or use pre
      prepared sterile bags of dialysis fluid. Expert commentary: Dialysis machine
      complexity is one of the hurdles reducing the number of patients opting for home
      hemodialysis and the introduction of the newer generation of dialysis machines
      designed for ease of use will hopefully increase the number of patients opting
      for home hemodialysis.

PMID- 29656668
TI  - Effect of smoking on gene expression profile - overall mechanism, impact on
      respiratory system function, and reference to electronic cigarettes.
AB  - Cigarette smoke has a crucial impact on transcriptome alteration by its effect on
      chromatin remodeling and DNA methylation status. The first mechanism is
      associated with the histone acetylation/deacetylation balance damage as a result
      of increased activity of NFKB and lipid peroxidation products, which lead to an
      increased activity of HATs and DNMTs and reduced HDACs. The second mechanism is
      connected with direct damaging of DNA by smoke components, activation of
      downstream repair mechanism and recruitment of DNMTs into the breakage site,
      'nicotine effect' and carbon monoxide (CO) activity on gene transcription and DNA
      methylation reduction. Cigarette smoking activates oxidative and inflammatory
      response and leads to uncontrolled structural changes in airways and alters gene
      expression. Such changes have a characteristic similar to that for COPD patients.
      Therefore, smoking is determined as a key risk factor for chronic respiratory
      disease development. Furthermore, electronic cigarettes, an alternative of
      tobacco cigarettes, also affect gene expression profile, which suggests some
      similarities in action mechanisms for both conventional and electronic
      cigarettes. However, there is only a limited number of trials discussing this
      issue and future investigations are needed.

PMID- 29656669
TI  - The effect of the facilitated tucking position on pain intensity during heel
      stick blood sampling in premature infants: a surprising result.
AB  - BACKGROUND: According to research findings, pain experience in neonatal period
      leads to short- and long-term complications that could be prevented by means of
      neonatal pain relief. Therefore, this study aimed to investigate the effect of
      facilitated tucking position on neonatal pain during heel prick blood sampling.
      METHODS: This is a cross over clinical trial was done on 40 premature neonates.
      During blood sampling, neonates were put in either facilitated tucking or routine
      positions randomly and Premature Infant Pain Profile (PIPP) was completed for
      each neonate. In the next sampling time, positions were changed and the process
      repeated. Data were analyzed using descriptive statistics, repeated measure
      ANOVA, and independent t-test. RESULTS: Results showed that the mean pain
      intensity in each position was increased during sampling (p = .0001) and after
      that was decreased significantly (p = .001), but before, during, and after
      sampling there was no significant difference between the two positions (p > .05).
      CONCLUSIONS: Overall findings showed that comparing neonates in the two
      positions; there was no significant difference in their pain intensity. These
      results are almost in contrast with many researches findings in this area. It
      seems there is a need to further investigation regarding this subject.

PMID- 29656670
TI  - Pain and Hardship Among Older Men: Examining the Buffering Effect of Medicare
      Insurance Coverage.
AB  - To better understand the health status of men in the United States, this study
      aimed to assess the association of hardship on the presence of and pain severity
      among men 50 years of age and older. Cross-sectional multivariate logistic
      regression analyses were conducted using the 2010 wave of the Health and
      Retirement Study ( N = 3,174) to assess the association between four hardship
      indicators and the presence of pain and pain severity among this sample of older
      men. Results suggest that the association between the presence of pain and
      hardship was statistically significant across all four indicators: ongoing
      financial hardship (CI [1.05, 1.63], p < .05), difficulty paying bills (CI [1.42,
      3.02], p < .001), food insecurity (CI [1.46, 3.15], p < .001), and not taking
      medication due to cost (CI [1.06, 1.66], p < .05), even after adjusting for all
      demographic factors. The associations between pain severity and ongoing financial
      strain (CI [1.23, 2.83], p < .01) and difficulty paying bills (CI [1.02, 3.18], p
      < .05) were statistically significant. Results also indicate that education was a
      buffer at all levels. In addition, the interactive effect of hardship and
      Medicare insurance coverage on pain severity was significant only for ongoing
      financial strain (CI [1.74, 14.33], p > .001) and difficulty paying bills (CI
      [1.26, 7.05], p < .05). The evidence is clear that each hardship indicators is
      associated with the presence of pain and across some of the indicators in pain
      severity among men aged 50 and older. In addition, these findings stress the
      importance that Medicare insurance plays in acting as a buffer to alleviate some
      of the hardships experienced by older men. These findings also highlight the
      association between the presence of pain and pain severity for the overall
      quality of life, health outcomes, and financial position of men in later life.

PMID- 29656671
TI  - The Reliable Change Index (RCI) of the WHO-5 in primary prevention of mental
      disorders. A measurement-based pilot study in positive psychiatry.
AB  - INTRODUCTION: Primary prevention of mental disorders is a major issue in positive
      psychiatry. Adjustment disorder is one of the very few discrete mental disorders
      linked to an etiological factor, namely psychosocial stressors given rise to a
      maladaptive reaction with a course of symptoms vanishing with the removal of the
      stressor. We have focused on a measurement-based method to prevent the
      development of an adjustment disorder. AIM: The aim of this study has been to
      analyze from an ongoing Worklife Barometer Survey in which the World Health
      Organization Well-Being Scale (WHO-5) has been applied to prevent distress
      leading to an adjustment disorder. METHODS: Persons identified with a decrease of
      15 points in their repeatedly WHO-5 ratings over three months were through a
      brief psychological intervention by experienced psychologists. The Reliable
      Change Index (RCI) was used to determine the clinically meaningful change in the
      WHO-5 ratings. RESULTS: Within the group who received the psychological
      intervention (N = 1338), 35% of the persons were identified by the RCI analysis
      to have developed a clinically reliable change in the WHO-5 at the time of the
      intervention. The remaining 65% of the persons obtained changes in the WHO-5
      which might be considered as spontaneous fluctuations. In the month after the
      intervention, the persons with a clinically reliable change in the WHO-5 were
      restored. CONCLUSION: In this measurement-based pilot study, the repeatedly WHO-5
      ratings identified a group of persons with a clinically reliable change in WHO-5
      and a clinically significant improvement after a brief psychological
      intervention.

PMID- 29656673
TI  - We should focus more on finding therapeutic targets for the non-inflammatory
      damage in MS - Yes.

PMID- 29656672
TI  - Screening of in vitro antimicrobial activity of plants used in traditional
      Indonesian medicine.
AB  - CONTEXT: In many regions of Indonesia, there are numerous traditional herbal
      preparations for treatment of infectious diseases. However, their antimicrobial
      potential has been poorly studied by modern laboratory methods. OBJECTIVE: This
      study investigates in vitro antimicrobial activity of 49 ethanol extracts from 37
      plant species used in Indonesian traditional medicine for treatment against
      Candida albicans, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa
      and Staphylococcus aureus. MATERIALS AND METHODS: The plants were collected from
      the Biopharmaca collection garden, Bogor, Indonesia. The plant material was
      dried, finely grounded, extracted using ethanol, concentrated, and the dried
      residue was dissolved in 100% DMSO. Antimicrobial activity was determined in
      terms of a minimum inhibitory concentration (MIC) using a broth microdilution
      method in 96-well microplates. RESULTS: The extract of Orthosiphon aristatus
      (Blume) Miq. (Lamiaceae) leaf produced the strongest antimicrobial effect,
      inhibiting the growth of C. albicans (MIC 128 MUg/mL), S. aureus (MIC 256
      MUg/mL), E. faecalis (MIC 256 MUg/mL) and P. aeruginosa (MIC 256 MUg/mL). The
      leaf extract of Woodfordia floribunda Salisb. (Lythraceae) also exhibited
      significant effect against C. albicans (MIC 128 MUg/mL), S. aureus (MIC 256
      MUg/mL) and E. faecalis (MIC 256 MUg/mL). Rotheca serrata (L.) Steane & Mabb.
      (Lamiaceae) leaf extract inhibited the growth of S. aureus (MIC 256 ug/mL) and C.
      albicans (MIC 256 ug/mL). DISCUSSION AND CONCLUSIONS: The leaf extract of O.
      aristatus and W. floribunda exhibited a significant anti-candidal effect.
      Therefore, both of these plants can serve as prospective source materials for the
      development of new anti-candidal agents.

PMID- 29656674
TI  - Psycho-social approach of perinatal palliative care.

PMID- 29656675
TI  - Professional burnout among medical students: Systematic literature review and
      meta-analysis.
AB  - BACKGROUND: This systematic review and meta-analysis aim to summarize the
      available evidence on the prevalence of professional burnout among medical
      students. METHODS: The review was performed according to the PRISMA guidelines.
      Databases were systematically searched for peer-reviewed articles, reporting
      burnout among medical students published between 2000 and 2017. The meta-analysis
      was conducted on the available data on burnout rates in medical students measured
      with the Maslach Burnout Inventory (MBI-HSS). RESULTS: Fifty-eight out of 3006
      studies were found eligible for inclusion. Twelve of these studies met the
      criteria for meta-analysis. Weighted mean values for the three sub-dimensions of
      the MBI-HSS were M = 22.93 (SD = 10.25) for Emotional Exhaustion, M = 8.88 (SD =
      5.64) for Depersonalization, and M = 35.11 (SD = 8.03) for Personal
      Accomplishment. Prevalence rates for professional burnout ranged from 7.0% to
      75.2%, depending on country-specific factors, applied instruments, cutoff
      criteria for burnout symptomatology. CONCLUSION: This review underlines the
      burden of burnout among medical students. Future research should explicitly focus
      on specific context factors and student group under investigation. Such efforts
      are necessary to control for context-dependent confounders in research on medical
      students' mental health impairment to enable more meaningful comparisons and
      adequate prevention strategies.

PMID- 29656677
TI  - Elevated levels of the circulatory ischemia-modified albumin in patients with
      polycystic ovary syndrome: a meta-analysis.
AB  - Oxidative stress (OS) has been reported to be associated with the pathogenesis of
      polycystic ovary syndrome (PCOS). Ischemia-modified albumin (IMA) levels in the
      circulation have been recently studied as a novel marker of OS. The studies in
      the literature on IMA levels in PCOS are inconsistent. This meta-analysis was
      conducted to compare circulatory IMA levels between PCOS patients and non-PCOS
      controls. Relevant studies were retrieved by online database and manual
      searching. The standardized mean differences (SMDs) with 95% confidence intervals
      (CIs) were obtained by a random-effects meta-analysis. The funnel plot analysis
      with Begg's and Egger's tests was used for publication bias. A total of nine
      studies were included in this meta-analysis. The results indicated that the serum
      IMA levels were significantly elevated in PCOS patients as compared to non-PCOS
      controls (SMD = 0.49, 95% CI = 0.23-0.75, Z = 3.75, p = .0002). A one-study leave
      out sensitivity analysis indicated that no single study had a significant
      influence on the overall outcome, suggesting the good validity and stability of
      these meta-analytic results. There was no evidence of publication bias as
      evidenced by the Egger (p = .28) and Begg's tests (p = .21). The present meta
      analysis suggests that IMA might be considered as a reliable and novel marker
      reflecting increased OS in PCOS.

PMID- 29656676
TI  - Cell penetrating peptides: a comparative transport analysis for 474 sequence
      motifs.
AB  - Delivering reagents into cells is a key demand in molecular medicine. The vehicle
      of choice is often cell penetrating peptides (CPPs), which can ferry conjugated
      cargo across membranes. Although numerous peptides have been shown to promote
      such uptake events, there has been no comprehensive comparison of individual
      performance under standardized conditions. We have devised a method to rapidly
      analyze the ability of a multitude of CPP conjugates to carry a model cargo into
      HeLa cells. Sequence information for 474 CPPs was collected from literature
      sources, and the respective peptides were synthesized and modified with
      carboxyfluorescein (FAM) as model cargo. All candidates were evaluated in an
      identical uptake test, and transport was quantified using cellular fluorescence
      intensities. Substantial differences in the ability to carry the fluorophore into
      the cells were observed, with transport performance differing by a factor of 70
      between the best CPP investigated and cargo alone. Strong correlations were
      observed between uptake efficiency and both sequence length and the presence of
      positive net charge. A compilation of the 20 top performers with regard to cargo
      delivery performance and cell compatibility is provided.

PMID- 29656678
TI  - Validation of the MedUseQ: A Self-Administered Screener for Older Adults to
      Assess Medication Use Problems.
AB  - BACKGROUND: Older adults taking multiple prescription and nonprescription drugs
      are at risk for medication use problems, yet there are few brief, self
      administered screening tools designed specifically for them. OBJECTIVE: The study
      objective was to develop and validate a patient-centered screener for community
      dwelling older adults. METHODS: In phase 1, a convenience sample of 57
      stakeholders (older adults, pharmacists, nurses, and physicians) participated in
      concept mapping, using Concept System(r) Global MAXTM, to identify items for a
      questionnaire. In phase 2, a 40-item questionnaire was tested with a convenience
      sample of 377 adults and a 24-item version was tested with 306 older adults, aged
      55 and older, using Rasch methodology. In phase 3, stakeholder focus groups
      provided feedback on the format of questionnaire materials and recommended
      strategies for addressing problems. RESULTS: The concept map contained 72
      statements organized into 6 conceptual clusters or domains. The 24-item screener
      was unidimensional. Cronbach's alpha was .87, person reliability was acceptable
      (.74), and item reliability was high (.96). CONCLUSION: The MedUseQ is a
      validated, patient-centered tool targeting older adults that can be used to
      assess a wide range of medication use problems in clinical and community settings
      and to identify areas for education, intervention, or further assessment.

PMID- 29656679
TI  - Three-dimensional reconstruction of fetal abnormalities using ultrasonography and
      magnetic resonance imaging.
AB  - OBJECTIVE: We aimed to compare three-dimensional (3D) fetal malformation images
      obtained using ultrasonography (US) and magnetic resonance imaging (MRI) on the
      same day during the third trimester of pregnancy. METHODS: Total 33 fetuses were
      selected from cases evaluated for malformations. Morphological abnormalities were
      first scanned using 3DUS. MRI was used to confirm the previous preliminary 3DUS
      findings, and diagnoses were confirmed postnatally. 3DUS scans were performed
      transabdominally using an Rab (4-8 L) probe, Voluson 730 Pro/Expert and E8
      (General Electric, Healthcare, Zipf, Austria). MRI was performed using a 1.5-T
      scanner (Magneton Avanto, Siemens, Erlangen, Germany) with a body coil. The 3D
      reconstruction of the structure of interest was manually performed from a True
      FISP sequence using an interactive pen tablet (Syngo multimodality 2009B,
      Siemens, Erlangen, Germany). RESULTS: Despite recent advancements in 3DUS, the
      quality of 3D images obtained from MRI was superior during the third trimester.
      3DUS had certain limitations, such as being influenced by the fetal position, the
      volume of amniotic fluid, and maternal obesity. Fetal movements during image
      acquisition were one of the main challenges for MRI. CONCLUSION: The quality of
      the 3D images obtained using MRI was superior to that of images obtained using US
      during the third trimester of pregnancy.

PMID- 29656680
TI  - Contraction frequency after administration of misoprostol in obese versus
      nonobese women.
AB  - OBJECTIVE: To examine impact of obesity on contraction frequency following
      misoprostol. Our hypothesis is that an increased volume of distribution reduces
      the bioavailability of misoprostol and may be an explanation for reduced
      efficacy. We examined the contraction frequency as a surrogate marker for
      bioavailability of misoprostol. STUDY DESIGN: We compared the rate of
      contractions at five time intervals in 313 subjects: prior to administration, and
      at four intervals post administration. We compared number of contractions in
      obese versus nonobese. As a planned secondary analysis, we then compared the rate
      of change in contractions per hour at four time intervals: a repeated measures
      analysis to compare the rate of change in contractions per hour over the 5-hour
      window controlling for race (White versus non-White) and parity (primiparous
      versus multiparous). General linear model and repeated measures analysis were
      conducted to report the parameter estimates, least square means, difference of
      least square means, and p values. RESULTS: Nonobese women presented with more
      contractions at baseline, 7 +/- 5 versus 4 +/- 5 c/h, p < .001. At all four time
      intervals after misoprostol administration obese women had fewer contractions per
      hour. The rate of change in contraction frequency after administration found
      obese women had a lower rate of increase in contraction frequency over the course
      of all four hours. We found a least squares means estimate (c/h): first hour (
      0.87), p = .08, second hour (-2.43), p = .01, third hour (-1.80), p = .96, and
      fourth hour (-2.98), p = .007. CONCLUSIONS: Obese women have a lower rate of
      contractions per hour at baseline and at four intervals after misoprostol
      administration. In addition, the rate of change in the increase in
      contractions/hour also was reduced in obese women versus nonobese women. This
      suggests a lower bioavailability of misoprostol in women with a larger volume of
      distribution which would likely impact the efficacy of misoprostol in obese women
      when given the same dose of misoprostol. It is unknown if higher misoprostol
      dosing would increase efficacy of misoprostol in obese women.

PMID- 29656681
TI  - Progress with modeling activity landscapes in drug discovery.
AB  - INTRODUCTION: Activity landscapes (ALs) are representations and models of
      compound data sets annotated with a target-specific activity. In contrast to
      quantitative structure-activity relationship (QSAR) models, ALs aim at
      characterizing structure-activity relationships (SARs) on a large-scale level
      encompassing all active compounds for specific targets. The popularity of AL
      modeling has grown substantially with the public availability of large activity
      annotated compound data sets. AL modeling crucially depends on molecular
      representations and similarity metrics used to assess structural similarity.
      Areas covered: The concepts of AL modeling are introduced and its basis in
      quantitatively assessing molecular similarity is discussed. The different types
      of AL modeling approaches are introduced. AL designs can broadly be divided into
      three categories: compound-pair based, dimensionality reduction, and network
      approaches. Recent developments for each of these categories are discussed
      focusing on the application of mathematical, statistical, and machine learning
      tools for AL modeling. AL modeling using chemical space networks is covered in
      more detail. Expert opinion: AL modeling has remained a largely descriptive
      approach for the analysis of SARs. Beyond mere visualization, the application of
      analytical tools from statistics, machine learning and network theory has aided
      in the sophistication of AL designs and provides a step forward in transforming
      ALs from descriptive to predictive tools. To this end, optimizing representations
      that encode activity relevant features of molecules might prove to be a crucial
      step.

PMID- 29656682
TI  - Potential utility of core needle biopsy in the diagnosis of IgG4-related
      dacryoadenitis and sialadenitis.

PMID- 29656683
TI  - Clinicopathologic analysis of 2736 salivary gland cases over a 11-year period in
      Southwest China.
AB  - OBJECTIVE: To investigate the epidemiological and clinicopathological
      characteristics of salivary gland tumors in southwest China in order to provide
      data for clinical diagnosis and other similar research. METHODS: Between March
      2007 and December 2017, 2736 patients with salivary gland tumors were recruited,
      the clinical and pathological data were retrospectively analyzed. RESULTS: A
      total of 2736 patients had a ratio of males to females of about 1.02:1. The ratio
      of benign to malignant tumors was 3.46:1. Pleomorphic adenoma and adenoid cystic
      carcinoma had 50.8% and 7.2%, respectively. About 65.4% tumors occurred in the
      parotid gland. There was no significant difference between the tumor in the left
      or right parotid and the use of cell phones. There were significant differences
      between gender and both the characteristics and locations of salivary gland
      tumors (p < .05). There were also significant differences between the
      pathological characteristics and location of the salivary gland (p < .05).
      CONCLUSIONS: The salivary gland benign and malignant tumors were more common in
      pleomorphic adenoma and adenoid cystic carcinoma, most occurred in the parotid
      gland. The minor gland tumors are lower than other parts of China. The incidence
      of parotid gland tumors is not related to the use of cell phones.

PMID- 29656684
TI  - Nationwide survey of severe postpartum hemorrhage in Japan: an exploratory study
      using the national database of health insurance claims.
AB  - AIM: The aim of this study was to investigate epidemiological and clinical
      aspects of severe postpartum hemorrhage (PPH) in Japan. METHODS: We used national
      health insurance claims from 2011 to 2014 provided by the Ministry of Health,
      Labour and Welfare. The data included randomly selected claims that covered 10%
      of all inpatients in October, a so-called sampling dataset (covering 1/120
      inpatients per year). We extracted claims for transfused blood, and further
      narrowed down the claims by names of diseases linked to PPH. As most referral
      obstetric facilities have adopted the diagnosis procedure combination (DPC)-based
      payment system while small-scale obstetric facilities have not (non-DPC
      facilities), the claims were also analyzed separately for DPC and non-DPC
      facilities. We assessed the incidence and causes of PPH, transfusion volume of
      red blood cells (RBC) and fresh frozen plasma (FFP), and surgical hemostatic
      management. RESULTS: The number of PPH cases that required blood transfusion in
      the sampling dataset was 29, 29, 32, and 36 in 2011, 2012, 2013, and 2014,
      respectively. The leading cause of PPH was uterine atony followed by placental
      abruption. Although no specific trends were observed for the volume of transfused
      RBC (1467 +/- 234 ml in 2014), there was a steady increase in the rate of FFP
      utilization in non-DPC facilities from 37% to 79% over the 4-year sampling
      period. Intrauterine balloon tamponade emerged in 2014. CONCLUSION: This
      nationwide survey indicates that the annual incidence of severe PPH is
      increasing. Furthermore, FFP has become more prevalent in small-scale obstetric
      facilities.

PMID- 29656685
TI  - Maternal hepatitis C (HCV) infection and Anti-D immunoglobulin therapy: study
      testing antibodies, RNA and Genotype of HCV in Baghdad.
AB  - INTRODUCTION: Hepatitis C virus (HCV) infection is a serious health problem. It
      is a major contributor to end-stage liver disease. Worldwide, 1-8% of all
      pregnant women were infected. Women with viral hepatitis may be at an increased
      risk of pregnancy complications. There are several obstetrics intervention acts
      as risk factors, which are specific to women pertaining the HCV infection; anti-D
      immunoglobulin (Ig) therapy may be one of them. Our objectives were to estimate
      the prevalence of HCV antibodies (anti-HCV), RNA, and genotype distribution among
      women with anti-D Ig therapy. MATERIALS AND METHODS: A cross sectional study was
      conducted. A sample of 154 Rhesus negative (Rh - ve) pregnant women regardless of
      the anti-D Ig therapy was collected. Anti-HCV were tested using third generation
      enzyme immunoassay (EIA-3) and immunoblot assay (Lia Tek-111), subsequently. In
      addition, 89 serum samples were subjected to molecular analysis using RT-PCR and
      DNA enzyme immunoassay (DEIA) method for the detection of HCV-RNA and genotypes.
      RESULTS: Anti-HCV, and HCV-RNA seroprevalence were significantly higher (17.1,
      35.5%) among women with anti-D Ig than their counter group (6.4, 13.16%), p =
      .038, .018, respectively. Significant direct positive dose response correlation
      (r = 0.78, p = .005) had been seen between number of anti-D Ig therapy and anti
      HCV seropositive rate. Anti-D Ig therapy act as a risk factor (odds ratio (OR) =
      3.01, 95%CI: 1.01-8.9) especially from the third dose onward. Women with anti-D
      Ig therapy were at higher risk (3.6 times more) of positive HCV-RNA (OR =3.6,
      95%CI =1.19-10.837). Genotype HCV-1b showed higher prevalent (52.9%) among the
      recipients of anti-D Ig therapy while genotype HCV-3a (6.6%) was the lowest.
      CONCLUSIONS: Our study showed that Anti-D immunoglobulin therapy acts as a risk
      factor for acquiring HCV infection. Screening for HCV should be recommended for
      all recipients of anti-D Ig. Not only HCV antibodies but HCV-RNA detection being
      recommended for the diagnosis of HCV infection. A brief rational: Pregnant women
      with HCV infection are at risk of adverse obstetric outcome. Anti-D Ig therapy
      may be a risk factor for HCV infection. Hence, we conducted a cross sectional
      study with the objectives to estimate the prevalence of HCV antibodies (anti
      HCV), RNA, and genotype distribution among women with anti-D Ig therapy. We found
      that anti-HCV and HCV-RNA seroprevalence were significantly higher in women with
      anti-D Ig. In addition, women with anti-D Ig therapy were 3.6 times more at risk
      of positive HCV-RNA with genotype HCV-1b showed higher prevalence. Therefore,
      anti-D Ig therapy is a risk factor for acquiring HCV infection and we recommend
      screening for HCV for all recipients of anti-D Ig. In addition, the diagnosis of
      HCV infection, should be made with HCV antibodies and HCV-RNA detection.

PMID- 29656687
TI  - Longitudinal evaluation of ventricular ejection fraction and NT-proBNP across
      heart failure subgroups.
AB  - OBJECTIVES: Left ventricular ejection fraction (EF) and N-terminal pro-B-type
      natriuretic peptide (NT-proBNP) are important surrogate markers of cardiac
      function and wall stress. Randomized trials of heart failure (HF) have shown
      improvements in survival in patients with reduced EF (<40%, HFrEF) but not with
      preserved EF (>=50%, HFpEF) or mid-range EF (40-49%, HFmrEF). Limited information
      is available on the trajectory of EF in contemporary heart failure management
      programs (HFMPs). DESIGN: 201 HF patients consecutively enrolled 2010-2011 in the
      outpatient-based HFMP of Skane University Hospital in Lund were included in the
      study. Probable etiology, EF, NT-proBNP and medications were assessed at baseline
      and 1 year after enrollment. RESULTS: HFrEF was the most common heart failure
      subgroup (78.1% of patients) in this HFMP, followed by HFmrEF (14.9%) and HFpEF
      (7.0%). The most common etiology was ischemic heart disease (IHD, 40.8%).
      Complete recovery of EF (>50%) was rare (14.1% of patients with HFrEF and 26.7%
      with HFmrEF), some degree of improvement was observed in 57.7% and 46.7% of
      patients. LVEF improved on average 9.1% in patients with HFrEF (p < .001) and NT
      proBNP decreased from 4,202 to 2,030 pg/ml (p < .001). A similar trend was
      noticed for the HFmrEF group but was not statistically significant. The
      improvement in LVEF was consistent across subgroups with HF attributable to IHD
      (6.2%), idiopathic dilated cardiomyopathy (7.1%) and tachycardia-induced HF
      (17.5%). CONCLUSIONS: This study provides estimates of the improvement in LVEF
      and NT-proBNP that can be expected with contemporary management across subgroups
      of HF and different etiologies in a contemporary HFMP.

PMID- 29656688
TI  - Sensory preservation in neck dissection: outcomes of a sub-sternocleidomastoid
      approach.
AB  - OBJECTIVE: Cutaneous anesthesia in early postoperative period is common after
      neck dissection even if the cervical nerve (CN) rootlets are preserved. The aim
      of this study was to evaluate if the preservation of the terminal branches of CNs
      using sub-sternocleidomastoid (SCM) approach combined with medially placed skin
      incision can prevent early postoperative anesthesia. MATERIAL AND METHODS: A
      retrospective chart review was performed on 129 neck dissections in 87 head and
      neck cancer patients. RESULTS: The early postoperative sensory preservation rates
      for the ear tab, submandibular, lateral neck, and sub-clavicular areas of CN
      rootlet-preserved necks (n = 86) were 75.6%, 20.9%, 74.4%, and 86.0%,
      respectively, compared with 37.2%, 2.3%, 2.3%, and 4.7%, respectively, in CN
      rootlet-resected necks (n = 43). In CN rootlet-preserved necks, the sub-SCM
      approach (n = 54) showed 81.5%, 27.8%, 92.6%, and 94.4% preservation rates,
      respectively, compared with 65.6%, 9.4%, 43.8%, and 71.9%, respectively, using
      the conventional subplatysmal approach (n = 32). The rates were significantly
      better in the submandibular, lateral neck, and sub-clavicular areas after sub-SCM
      approach. CONCLUSIONS: Preservation of CN rootlets is a required element for
      sensory preservation in neck dissection. The sub-SCM approach can effectively
      prevent early postoperative cutaneous anesthesia following CN-preserving neck
      dissection.

PMID- 29656686
TI  - Lipopolysaccharide from Rhodobacter sphaeroides (TLR4 antagonist) attenuates
      hypersensitivity and modulates nociceptive factors.
AB  - CONTEXT: Accumulating evidence has demonstrated that Toll-like receptors (TLRs),
      especially TLR4 localized on microglia/macrophages, may play a significant role
      in nociception. OBJECTIVE: We examine the role of TLR4 in a neuropathic pain
      model. Using behavioural/biochemical methods, we examined the influence of TLR4
      antagonist on levels of hypersensitivity and nociceptive factors whose
      contribution to neuropathy development has been confirmed. MATERIALS AND METHODS:
      Behavioural (von Frey's/cold plate) tests were performed with Wistar male rats
      after intrathecal administration of a TLR4 antagonist (LPS-RS ULTRAPURE (LPS
      RSU), 20 MUG: lipopolysaccharide from Rhodobacter sphaeroides, InvivoGen, San
      Diego, CA) 16 H and 1 h before chronic constriction injury (cci) to the sciatic
      nerve and then daily for 7 d. three groups were used: an intact group and two cci
      exposed groups that received vehicle or LPS-RSU. tissue [spinal cord/dorsal root
      ganglia (DRG)] for western blot analysis was collected on day 7. RESULTS: The
      pharmacological blockade of TLR4 diminished mechanical (from ca. 40% to 16% that
      in the INTACT group) and thermal (from ca. 51% to 32% that in the INTACT group)
      hypersensitivity despite the enhanced activation of IBA-1-positive cells in DRG.
      Moreover, LPS-RSU changed the ratio between IL-18/IL-18BP and MMP-9/TIMP-1 in
      favour of the increase of antinociceptive factors IL-18BP (25%-spinal; 96%-DRG)
      and TIMP-1 (15%-spinal; 50%-DRG) and additionally led to an increased IL-6 (40%
      spinal; 161%-DRG), which is known to have analgesic properties in neuropathy.
      CONCLUSIONS: Our results provide evidence that LPS-RSU influences pain through
      the expression of TLR4. TLR4 blockade has analgesic properties and restores the
      balance between nociceptive factors, which indicates its engagement in neuropathy
      development.

PMID- 29656689
TI  - Risk factors for postpartum urinary retention after vaginal delivery at term
      without epidural anesthesia.
AB  - OBJECTIVE: We performed a retrospective case-control study of vaginal delivery at
      term without epidural anesthesia to identify clinical predictions of postpartum
      urinary retention (PUR). METHODS: We reviewed the obstetric records of all
      singleton vaginal deliveries at Japanese Red Cross, Katsushika Maternity Hospital
      form January 2016 through December 2017. RESULTS: There were 58 women (2.4%)
      complicated by PUR and 2391 women without PUR. A multivariate analysis revealed
      nulliparity, instrumental delivery, and episiotomy as independent risk factors
      for PUR (nulliparity: adjusted OR 2.39, 95%CI 1.2-4.8, p = 0.01; instrumental
      delivery: 3.53, 95%CI 1.9-6.7, p < .01, episiotomy: adjusted OR 1.96, 95%CI 1.0
      3.8, p = .04). While, urination (or urethral catheterization) within 1 hour
      before delivery revealed as independent prevention factor for PUR (adjusted OR
      0.54, 95%CI 0.30-0.99, p = .048). CONCLUSIONS: The risk factors identified in our
      institute seemed to approximately similar to those observed in the institutes
      capable of performing epidural anesthesia. In addition, urination just before
      delivery seemed to be an independent prevention factor for PUR.

PMID- 29656690
TI  - Maternal blood endotoxin activity in pregnancies complicated by preterm premature
      rupture of membranes.
AB  - OBJECTIVE: To compare maternal blood endotoxin activity (EA) in women with
      preterm premature rupture of membranes (PPROM) with gestational age (GA) matched
      controls; to evaluate serial EA till birth in PPROM and its correlation with
      latency to delivery. METHODS: We followed singleton preterm pregnancies from
      admission with PPROM until birth. Uncomplicated, GA-matched pregnancies served as
      controls. Demographics, birth and neonatal outcomes were collected. EA (EAATM)
      was assessed serially in PPROM and at study entry in controls. EA was compared
      using Mann Whitney and Wilcoxon tests, p value <.05 was considered significant.
      RESULTS: We recruited 20 cases of PPROM and 20 controls. Demographics were
      similar between groups. Mean GA of PPROM was 29.0 +/- 2.2 weeks and median
      latency was 7.5 (IQR 14.1) weeks. Median EA at admission following PPROM was
      significantly elevated over controls (0.43 (0.18) versus 0.36 (0.2); p < .02).
      Overall there was no difference in median EA at admission and in labor (0.43
      (0.18) versus 0.33 (0.21); p = .2) following PPROM. However, on comparing cases
      with latency to delivery <=7 days (n = 10) versus >7 days (n = 10), there was a
      significant drop in EA in the latter group (0.44 (0.2) versus 0.34 (0.2); p <
      .004). CONCLUSIONS: EA in PPROM represents a promising biomarker in predicting
      the clinical evolution of preterm birth.

PMID- 29656691
TI  - We should focus more on finding therapeutic targets for the non-inflammatory
      damage in MS - No.

PMID- 29656692
TI  - General practitioners' prescriptions of benzodiazepines, Z-hypnotics and opioid
      analgesics for elderly patients during direct and indirect contacts. A cross
      sectional, observational study.
AB  - OBJECTIVE: To describe Norwegian general practitioners' (GPs') prescription
      patterns of benzodiazepines, Z-hypnotics and opioid analgesics (BZO-drugs) to
      elderly (>=70 years) patients. DESIGN, SUBJECTS AND SETTING: Cross sectional,
      observational study. Contact- and prescription data from 148 Norwegian GPs,
      issued for elderly patients during eight months in 2008. GP-patient contacts were
      categorized as direct contacts (DC: face-to-face consultations) or indirect
      contacts (IC: via third party, phone or mail). Explanatory variables were
      characteristics linked to the GPs, patients, and practices. During analyses, GPs'
      number of listed patients, share of which for elderly patients, and total number
      of patient consultations during the period (proxy for practice activity), were
      categorized in quintiles (Q1-5) by number of GPs. MAIN OUTCOME MEASURES: Number
      of BZO-drug prescriptions and quantities issued during direct- and indirect GP
      patient contacts. RESULTS: In total, 62% of BZO-prescriptions were issued during
      ICs. Of all prescriptions, 66% were large quantum packages (50 tablets or more),
      62% out of which were prescribed during ICs. During the study period, 50% of the
      patients received repeat prescriptions. Prescribing during ICs was associated
      with low over all practice activity (Q1) and many (Q5) older patients on the GP's
      lists. CONCLUSION: GPs' BZO-drug prescribing to elderly occur more frequently
      during ICs than within DCs, and are more commonly issued as large quantity
      packages. This indicates that regular- or long-term use among elderly is common,
      contrasting with previous and current national guidelines, which recommend
      regular clinical assessments and short time or intermittent use of BZO-drugs. Key
      Points GPs frequently prescribe benzodiazepines, Z-hypnotics and opioid (BZO)
      drugs for elderly people. BZO-drugs are frequently issued during indirect GP
      patient contacts and in relatively large quantities, indicating regular or long
      term use. GPs' BZO-drug prescribing patterns contrast with national guidelines
      recommending clinical assessment and short time or intermittent use of BZO-drugs.

PMID- 29656693
TI  - The effect of first clinical assignments on prelicensure nursing students'
      attitudes toward older people: an observational study.
AB  - BACKGROUND: With the global population growth of older people, health care needs
      nurses interested in caring for this population. Studies have found a
      relationship between attitudes toward older people and career choices. AIM: The
      aim of this study was to determine the effect first clinical experiences had on
      nursing students' attitudes toward older people. DESIGN/METHOD: Using an
      observational research design, first-semester nursing students (n = 53) from the
      United States were assigned to one of two groups based on sequencing of clinical
      assignments. Participants completed the Refined Aging Semantic Differential scale
      three times their first semester. RESULTS: Students with exposure to long-term
      and then the acute care setting showed linear improvement in their attitudes
      toward older people. In addition, a significant improvement in attitudes over
      time was found (F[2, 96] = 3.56, p = .032) at two time measurements. CONCLUSION:
      This study showed that novice students may not recognize the differences in acute
      and long-term nursing care. Results may assist nursing educators designing
      curricula.

PMID- 29656694
TI  - Pre-specialization - Considerations for more focused and personalized educational
      modules in the twenty-first century.
AB  - BACKGROUND: This essay provides a multidisciplinary discussion of the current
      medical education curriculum and the increasing need to adapt it to our rapidly
      evolving and expanding healthcare environment. METHODS: Thorough literature
      search on the topic of medical school curriculum, ranging from its historical
      origins to contemporary practice as well as statistics, was conducted. RESULTS:
      The authors give a brief historical overview of and rationale behind the current
      structure of the medical education system in America. The recent trends towards
      information overload and rapid evolution of the evidence-base are discussed.
      Specialization, as a means of responding to the burgeoning abundance of
      information in medicine, is described. The authors further provide current as
      well as foreseeable limitations of today's medical training paradigm as the trend
      towards specialization continues. The potential negative influences of a
      specialist-focused training paradigm on the overall length of training and the
      degree of autonomy exercised by generalists are described. A proposal toward pre
      specialization at the level of medical school is introduced and elaborated upon.
      The authors incorporate social psychology principles and analyze trends toward
      career specialization, highlighting potential benefits to a different-size-for
      all approach. The importance of optionality and flexibility of such a curriculum
      is emphasized. CONCLUSIONS: The authors describe the inevitable trend toward
      specialization, and the need to fundamentally re-configure American medical
      education system to behoove trainees' experiences and quality of training during
      the 21st century.

PMID- 29656695
TI  - ?

PMID- 29656697
TI  - We should focus more on finding therapeutic targets for the non-inflammatory
      damage in MS - Commentary.

PMID- 29656696
TI  - The impact of changes in leisure time physical activity on changes in
      cardiovascular risk factors: results from The Finnmark 3 Study and SAMINOR 1,
      1987-2003.
AB  - OBJECTIVE: The aim of this study was to examine the associations between changes
      in leisure time physical activity and changes in cardiovascular risk factors over
      16 years and whether they differ between two ethnic groups in Norway. METHODS:
      Data were extracted from two population-based studies. Altogether, 3671 men and
      women participated in both surveys, and 30% reported being of Sami ethnicity.
      Leisure time physical activity was self-reported, and cardiovascular risk factors
      were measured. ANCOVA analysis was used to examine associations between changes
      in physical activity and changes in cardiovascular risk factors. RESULTS: After
      adjustment for age, sex, smoking, ethnicity and respective baseline values,
      favourable changes in body mass index (BMI) and levels of triglycerides were most
      pronounced in those who were active in both surveys (p < 0.05) whereas the
      opposite was the situation for cholesterol levels (p = 0.003). Changes in
      systolic blood pressure, diastolic blood pressure and resting heart rate were not
      significantly associated with change in physical activity. Ethnicity did not
      influence the associations between physical activity and cardiovascular risk
      factors. CONCLUSION: Traditional cardiovascular risk factors were to a small
      extent associated with change in leisure time physical activity. Persistent
      physical activity was associated with beneficial changes in BMI and
      triglycerides.

PMID- 29656698
TI  - Association Between a Melatonin Receptor 1B Genetic Polymorphism and Its Protein
      Expression in Gestational Diabetes Mellitus.
AB  - AIMS: This study was conducted to investigate the relationship between a genetic
      polymorphism and the expression of melatonin receptor 1B (MTNR1B) in the placenta
      of Han Chinese women with gestational diabetes mellitus (GDM). METHODS: In this
      study, 215 patients with GDM and 243 healthy controls were genotyped using direct
      sequencing for the MTNR1B single-nucleotide polymorphism rs10830963. The
      expression of MTNR1B in placenta was detected by immunohistochemistry and Western
      blotting. The association of rs10830963 with the expression of MTNR1B, plasma
      glucose, and insulin levels as well as blood lipid levels was investigated.
      RESULTS: The genotype and allele frequencies of rs10830963 were significantly
      different between women with GDM and controls ( P < .05). Fasting blood glucose,
      fasting insulin, and homeostasis model assessment for insulin resistance in women
      with GDM with the GG and GC genotypes were significantly higher than those with
      the CC genotype ( P < .05). The expression level of MTNR1B in placenta was
      significantly higher in the GDM group than in the control group ( P < .05). The
      expression of MTNR1B was significantly higher in all participants with the GG and
      GC genotypes (1.31 [0.74]) than in pregnant women with the CC genotype (0.92
      [0.52], P < .05). CONCLUSIONS: The genetic polymorphism rs10830963 in MTNR1B and
      its protein expression levels in placenta are associated with an increased risk
      of developing GDM. Furthermore, rs10830963 may tag a molecular mechanism leading
      to insulin resistance in Han Chinese women with GDM.

PMID- 29656699
TI  - Hybrid polycaprolactone/polyethylene oxide scaffolds with tunable fiber surface
      morphology, improved hydrophilicity and biodegradability for bone tissue
      engineering applications.
AB  - In the present study, we attempt to modify Polycaprolactone (PCL) by blending it
      with a water soluble polymer Polyethyleneoxide (PEO) having two different
      molecular weights (Mv ~1,00,000 and 6,00,000) using electrospinning technique.
      The effect of PEO molecular weight and blend ratio on fiber morphology, porosity,
      surface wettability, static and dynamic mechanical properties of PCL was
      investigated. In vitro degradation studies in phosphate buffer saline (PBS) at 37
      degrees C demonstrated formation of pores on fiber surface especially in blend
      scaffolds with 50:50 ratios. In vitro studies using human osteoblast sarcoma
      (hOS) cell lines on blend scaffolds showed improved cellular response with good
      cell adhesion, viability and proliferation. The study revealed that incorporation
      of PEO on PCL scaffolds complemented the properties of PCL and facilitated
      fabrication of scaffolds with improved hydrophilicity, mechanical property and
      tunable degradation profile with better cell viability which makes it an ideal
      candidate for bone tissue engineering applications.

PMID- 29656700
TI  - HIF-2alpha-ILK Is Involved in Mesenchymal Stromal Cell Angiogenesis in Multiple
      Myeloma Under Hypoxic Conditions.
AB  - Mesenchymal stromal cells are proven to be likely induce the angiogenic response
      in multiple myeloma and thus represent an enticing target for antiangiogenesis
      therapies for multiple myeloma. Substantial evidence indicates that angiogenesis
      in multiple myeloma is complex and involves direct production of angiogenic
      cytokines by abnormal plasma cells and these B-cell neoplasia generated
      pathophysiology change within the microenvironment. In this study, we
      demonstrated that mesenchymal stromal cells cultured with U266/Lp-1 under hypoxic
      conditions resulted in an increased alpha-smooth muscle actin expression and high
      productive levels of both hypoxia-inducible factor-2alpha and integrin-linked
      kinase proteins. Moreover, inhibition of hypoxia-inducible factor-2alpha by Small
      interfering RNA (siRNA) in mesenchymal stromal cells decreased the protein levels
      of both alpha-smooth muscle actin and integrin-linked kinase after mesenchymal
      stromal cells cultured with U266 under hypoxic conditions. We further
      demonstrated that transfection of integrin-linked kinase-siRNA reduced the
      protein level of alpha-smooth muscle actin and attenuated angiogenesis in vitro
      by decreasing the attachment of Q-dot labeled cells and secretion of angiogenic
      factors. In conclusion, our research showed that mesenchymal stromal cells
      cultured with myeloma cells under hypoxia participated in the angiogenesis of
      multiple myeloma, which is regulated by the hypoxia-inducible factor-2alpha
      integrin-linked kinase pathway. Thus, targeting integrin-linked kinase may
      represent an effective strategy to block hypoxia-inducible factor-2alpha-induced
      angiogenesis in the treatment of multiple myeloma.

PMID- 29656702
TI  - Kainic acid in the seaweed Palmaria palmata (dulse).
AB  - Twenty samples of the seaweed Palmaria palmata (dulse) purchased mainly from
      commercial Internet shops on the European market were analysed by a liquid
      chromatograph coupled with a tandem mass spectrometer method for the content of
      kainic acid, a naturally occurring neurotoxic compound in P. palmata. Kainic acid
      levels in the samples ranged widely from trace levels to approximately 560 MUg g
      1 dry weight.

PMID- 29656701
TI  - Estimated Cost to a Restaurant of a Foodborne Illness Outbreak.
AB  - OBJECTIVES: Although outbreaks of restaurant-associated foodborne illness occur
      periodically and make the news, a restaurant may not be aware of the cost of an
      outbreak. We estimated this cost under varying circumstances. METHODS: We
      developed a computational simulation model; scenarios varied outbreak size (5 to
      250 people affected), pathogen (n = 15), type of dining establishment (fast food,
      fast casual, casual dining, and fine dining), lost revenue (ie, meals lost per
      illness), cost of lawsuits and legal fees, fines, and insurance premium
      increases. RESULTS: We estimated that the cost of a single foodborne illness
      outbreak ranged from $3968 to $1.9 million for a fast-food restaurant, $6330 to
      $2.1 million for a fast-casual restaurant, $8030 to $2.2 million for a casual
      dining restaurant, and $8273 to $2.6 million for a fine-dining restaurant,
      varying from a 5-person outbreak, with no lost revenue, lawsuits, legal fees, or
      fines, to a 250-person outbreak, with high lost revenue (100 meals lost per
      illness), and a high amount of lawsuits and legal fees ($1 656 569) and fines
      ($100 000). This cost amounts to 10% to 5790% of a restaurant's annual marketing
      costs and 0.3% to 101% of annual profits and revenue. The biggest cost drivers
      were lawsuits and legal fees, outbreak size, and lost revenue. Pathogen type
      affected the cost by a maximum of $337 000, the difference between a Bacillus
      cereus outbreak (least costly) and a listeria outbreak (most costly).
      CONCLUSIONS: The cost of a single foodborne illness outbreak to a restaurant can
      be substantial and outweigh the typical costs of prevention and control measures.
      Our study can help decision makers determine investment and motivate research for
      infection-control measures in restaurant settings.

PMID- 29656703
TI  - The ethics of concurrent care for children: A social justice perspective.
AB  - Recent estimates indicate that over 40,000 children die annually in the United
      States and a majority have life-limiting conditions. Children at end of life
      require extensive healthcare resources, including multiple hospital readmissions
      and emergency room visits. Yet, many children still suffer from symptoms at end
      of life-including fatigue, pain, dyspnea, and anxiety-with less than 10% of these
      children utilizing hospice care services. A critical barrier to pediatric hospice
      use was the original federal regulations associated with the hospice care that
      required a diagnosis of 6 months to live and the discontinuation of all curative
      treatments. The Concurrent Care Provision of the United States' Affordable Care
      Act eliminated the need to forgo curative therapies in order to enroll in hospice
      for children in Medicaid or Children's Health Insurance Program. Concurrent care
      for children can help mitigate the tension families experience in choosing
      between essential forms of care, as well as contribute to improved end-of-life
      outcomes for the child and possibly bereavement outcomes for the family.
      Understanding concurrent care for children from a social justice perspective has
      important advocacy and research implications for hospice and palliative care
      clinicians providing care for children and their families. We apply Powers and
      Faden's theory of social justice "as the moral foundation of public health and
      health policy" to the provision of concurrent care to children near end of life
      and families in the United States. The goals of applying this theory are to
      explore additional insights and perspectives into concurrent care policy may
      provide and to assess the usefulness of this theory when applied to end-of-life
      health policy. We argue that concurrent care policy is socially just since it has
      potential to promote well-being in vulnerable children and families and can limit
      the inequity children at end-of-life experience in access to high-quality hospice
      care.

PMID- 29656704
TI  - Phenomenon of moral distress through the aspect of interpretive interactionism.
AB  - BACKGROUND: Most previous studies on moral distress focused on the factors that
      cause moral distress, paying inadequate attention to the moral conflict of
      nurses' values, the physician-nurse power hierarchy, and the influence of the
      culture. RESEARCH OBJECTIVE: To analyze the main causes for moral distress with
      interpretive interactionism. RESEARCH DESIGN: A qualitative study was adopted.
      PARTICIPANTS: Through purposeful sampling, 32 nurses from 12 different
      departments were chosen as the samples. Ethical considerations: Approval from the
      Institutional Review Board of the Kaohsiung Medical University Hospital.
      FINDINGS: Moral distress is likely to occur in the following clinical situations:
      patients have no idea about their diseases; the medical decisions fail to meet
      the optimum benefit of patients; and patients with terminal cancers are not given
      a proper death. The reason why nurses become trapped in moral distress is that
      they fail to achieve moral goodness. Inadequate confidence, the physician-nurse
      power hierarchy, and the Oriental culture affect nurses' goodness-based intention
      for patients, which deteriorates moral distress. DISCUSSION: The main cause for
      moral distress is the moral goodness of nurses. If nurses' goodness-based
      intention for patients is inconsistent with the moral objective of achieving
      optimum benefit for patients, it leads to moral distress. Culture is an essential
      background factor of care for patients. In the Oriental culture, family members
      influence patients' right to know about their diseases, the choice of treatment,
      and patients' autonomy of not receiving cardio-pulmonary resuscitation. This
      results in moral distress in medical care. CONCLUSION: The occurrence of moral
      distress demonstrates that nurses have moral characteristics such as goodness and
      caring. It is suggested that appropriate educational strategies can be adopted to
      weaken the power hierarchy between physicians and nurses and enhance nurses'
      confidence and cultural sensitivity, so as to reduce the moral distress of
      nurses.

PMID- 29656705
TI  - Suppressive effects of neonatal bisphenol A on the neuroendocrine system.
AB  - The aim of this study was to assess the effects of neonatal bisphenol A (BPA)
      administration on neuroendocrine features (the thyroid-brain axis). BPA (20 or 40
      ug/kg) was orally administered to juvenile male albino rats ( Rattus norvegicus)
      from postnatal days (PNDs) 15 to 30. Both doses resulted in lower serum thyroxine
      (T4), triiodothyronine (T3), and growth hormone levels and higher thyrotropin
      level than the control levels at PND 30. In the neonatal cerebellum and cerebrum,
      vacuolation, pyknosis, edema, degenerative changes, and reductions in the size
      and number of the cells were observed in both treated groups. Alternatively,
      elevations in oxidative markers (lipid peroxidation, nitric oxide, and hydrogen
      peroxide [H2O2]) at both dose levels were recorded at PND 30, along with
      decreased activities of antioxidant markers (ascorbic acid, total thiol [t-SH],
      glutathione, glutathione peroxidase, glutathione reductase, glutathione-S
      transferase, and catalase) with respect to control levels. Thus, the BPA-induced
      hypothyroid state may disturb the neonatal thyroid-brain axis via production of
      free radicals, and this could damage the plasma membrane and cellular components,
      delaying cerebrum and cerebellum development.

PMID- 29656706
TI  - Relationship Between Self-Assessed Fidelity and Self-Reported Employment in the
      Individual Placement and Support Model of Supported Employment.
AB  - OBJECTIVE: A growing body of literature demonstrates that high-fidelity
      implementation of the individual placement and support (IPS) model of supported
      employment increases the chances of achieving desired outcomes. This study
      examined the relationship between IPS fidelity, as self-reported by program
      sites, and employment outcomes and determined whether this relationship was
      maintained over time. METHODS: A total of 78 outpatient programs in New York
      State provided data on self-reported IPS fidelity and employment outcomes.
      Pearson correlations were used to determine the relationship between fidelity
      scores and competitive employment rates. A mixed-effects model examined the
      relationship between repeated fidelity and employment measures over time.
      RESULTS: A significant positive relationship was found between better self
      reported IPS fidelity and greater employment. The relationship between IPS
      fidelity and employment was sustained over time (up to one year). CONCLUSIONS:
      Higher-fidelity implementation of the IPS model, as self-assessed by program
      sites, was associated with higher employment rates, which were sustained over
      time.

PMID- 29656707
TI  - Three-Year Retention in Buprenorphine Treatment for Opioid Use Disorder Among
      Privately Insured Adults.
AB  - OBJECTIVE: This study examined factors related to retention in buprenorphine
      treatment for opioid use disorder (OUD) among privately insured patients.
      METHODS: Patients with OUD who were newly started on buprenorphine during federal
      fiscal year (FY) 2011 were identified in a national private insurance claims
      database (MarketScan), and treatment retention (filled buprenorphine
      prescriptions) was evaluated through FY 2014. Proportional hazards models were
      used to examine demographic, clinical, and service use characteristics in FY
      2011, including ongoing insurance coverage, associated with discontinuation of
      treatment. RESULTS: Of 16,190 patients with OUD newly started on buprenorphine in
      FY 2011, 45.0% were retained in treatment for more than one year, and 13.7% for
      more than three years (mean+/-SD duration of retention=1.23+/-1.16 years). During
      the first three years after buprenorphine initiation, 49.3% (N=7,988) disenrolled
      from their insurance plan. Cox proportional hazards models showed that for every
      30 days of enrollment, the risk of discontinuation declined by 10% (hazard ratio
      [HR]=.90, 95% confidence interval [CI]=.90-.91). FY 2011 factors reducing
      discontinuation risk were age greater than the median (HR=.90, CI=.87-.93) and
      receipt of outpatient psychotherapy (HR=.90, CI=.86-.92); increased risk was
      associated with psychiatric hospitalization (HR=1.30, CI=1.24-1.36), emergency
      department visits (HR=1.07, CI=1.04-1.14), and additional substance use disorders
      (HR=1.05, CI=1.01-1.10). CONCLUSIONS: Buprenorphine treatment retention declined
      markedly in the first year and was substantially lower than in comparable studies
      from publicly funded health care systems, apparently largely due to
      disenrollment. The association of psychotherapy with greater retention suggests
      that it may be an important complement to opioid agonist treatment.

PMID- 29656708
TI  - Outcomes of a Peer Mentor Intervention for Persons With Recurrent Psychiatric
      Hospitalization.
AB  - OBJECTIVE: This article presents findings from a randomized controlled trial of a
      peer support mentorship intervention designed for individuals with serious mental
      illness and frequent, recurrent psychiatric hospitalizations. METHODS: Seventy
      six individuals who were diagnosed as having a major psychotic or mood disorder
      and who had at least two psychiatric hospitalizations or more than three
      emergency department visits within the 18 months prior to the index
      hospitalization participated in this trial. Participants were randomly assigned
      to one of two conditions: standard care or a peer mentor plus standard care.
      Substance use, psychiatric symptoms, psychosocial functioning, and hope were
      assessed at baseline and at three and nine months after hospital discharge.
      RESULTS: Participants assigned to the peer mentor condition reported
      significantly greater reductions in substance use and psychiatric symptoms and
      greater improvements in functioning compared with participants assigned to
      standard care. Moreover, participants in the peer mentor program remained out of
      the hospital for significantly longer periods of time compared with those
      assigned to standard care. CONCLUSIONS: Peer services for those who are
      hospitalized recurrently hold promise as an effective component of behavioral
      health care for persons with serious mental illnesses.

PMID- 29656709
TI  - Envisioning Transformation in VA Mental Health Services Through Collaborative
      Site Visits.
AB  - This column reviews the unique contributions of multiple partners in establishing
      a standardized site visit process to promote quality improvement in mental health
      care at the Veterans Health Administration. Working as a team, leaders in policy
      and operations, staff of research centers, and regional- and facility-level
      mental health leaders developed a standardized protocol for evaluating mental
      health services at each site and using the data to help implement policy goals.
      The authors discuss the challenges experienced and lessons learned in this
      systemwide process and how this information can be part of a framework for
      improving mental health services on a national level.

PMID- 29656710
TI  - Contact With Mental Health Services Prior to Suicide: A Systematic Review and
      Meta-Analysis.
AB  - OBJECTIVE: Access to mental health care is regarded as a central suicide
      prevention strategy. This is the first systematic review and meta-analysis of the
      prevalence of contact with mental health services preceding suicide. METHODS: A
      systematic search for articles reporting prevalence of contact with mental health
      services before suicide was conducted in MEDLINE and PsycINFO, restricted to
      studies published from January 1, 2000, to January 12, 2017. A random-effects
      meta-analysis with double arcsine transformations was conducted, with meta
      regression used to explore heterogeneity. RESULTS: Thirty-five studies were
      included in the systematic review, and 20 were included in the meta-analysis.
      Among suicide decedents in the population, 3.7% (95% confidence interval
      [CI]=2.6%-4.8%) were inpatients at the time of death. In the year before death,
      18.3% (CI=14.6%-22.4%) of suicide decedents had contact with inpatient mental
      health services, 26.1% (CI=16.5%-37.0%) had contact with outpatient mental health
      services, and 25.7% (CI=22.7%-28.9%) had contact with inpatient or outpatient
      mental health services. Meta-regression showed that women had significantly
      higher levels of contact compared with men and that the prevalence of contact
      with inpatient or outpatient services increased according to the sample year.
      CONCLUSIONS: Contact with services prior to suicide was found to be common and
      contact with inpatient or outpatient mental health services before suicide seems
      to be increasing. However, the reviewed studies were mainly conducted in Western
      European and North American countries, and most studies focused on psychiatric
      hospitalization, which resulted in limited data on contact with outpatient
      services. Better monitoring and data on suicides that occur during and after
      treatment seem warranted.

PMID- 29656711
TI  - The Fierce Urgency of Now: Improving Outcomes for Justice-Involved People With
      Serious Mental Illness and Substance Misuse.
AB  - People with serious mental illness are more likely to be arrested multiple times
      for the same crime, spend more time in jail before adjudication, serve longer
      sentences, and have higher recidivism rates than those without mental illness.
      Several conceptual foundations, such as the sequential intercept model and the
      risk-needs-responsivity model, have been developed to help communities address
      the overrepresentation of people with mental illness in the criminal justice
      system. The Stepping Up Initiative is a national effort to enlist counties to
      commit to reduce the number of people with mental illness in their jails. The
      21st Century Cures Act has created opportunities to fund community treatment and
      help people with serious mental illness live a productive life in their
      community. Public officials may need to be shown the substantial cost savings
      likely to accrue from an investment in effective community treatment. The time to
      act is now.

PMID- 29656712
TI  - Isolated splenic lymphangioma presenting as a huge mass causing anemia and
      abdominal distension in an adult patient: a case report.
AB  - BACKGROUND: Lymphangiomas are uncommon benign lesions of lymphatic vessels very
      rarely affecting the spleen. Isolated involvement of the spleen in adult patients
      is rarely reported. CASE PRESENTATION: We report a case of a 40-year-old Arabic
      woman who presented with a 25-cm abdominal mass, fatigue, and anemia evolving for
      6 months. Her physical examination revealed anemic syndrome and an enormous
      splenomegaly extending beyond the umbilical area. An abdominal computed
      tomographic scan showed a 25-cm splenic mass with multiple hypodense nodules
      without enhancement after contrast injection. A surgical total splenectomy was
      performed. Histopathological analysis led to the diagnosis of cystic splenic
      lymphangioma. The patient's postoperative course was uneventful, and she was
      discharged from the hospital. CONCLUSIONS: Isolated splenic lymphangioma in adult
      patients is very rare. The preoperative diagnosis is challenging because imaging
      techniques are not specific. Pathological analysis of the resected specimen is
      the only effective way to render the definitive diagnosis. Splenic lymphangiomas
      have a benign course after complete surgical resection.

PMID- 29656713
TI  - Symptom management, nutrition and hydration at end-of-life: a qualitative
      exploration of patients', carers' and health professionals' experiences and
      further research questions.
AB  - BACKGROUND: Symptom management is an essential aspect of palliative and end-of
      life care, but evidence suggests that patients' symptoms may not always be
      relieved, causing significant harm to patients and magnifying their relatives'
      distress. A growing body of evidence focuses on symptom management at the end-of
      life, but research funding for palliative care remains disproportionately low. It
      is therefore crucial that research funding is targeted at areas of importance to
      patients and relatives. The Palliative and end-of-life care Priority Setting
      Partnership (PeolcPSP) undertook a UK-wide free-text survey to establish research
      priorities within palliative and end-of-life care and disseminated its results in
      2015. Much of the data were related more broadly to personal perceptions and
      experiences rather than specific research questions. The aim of this article is
      to report on a supplementary analysis exploring the experiences and questions of
      PeolcPSP survey respondents regarding symptoms, hydration and nutrition. METHODS:
      The PeolcPSP data (n = 1403) were coded by a team of qualitative researchers in a
      supplementary analysis. There were 190 responses that related to symptoms,
      nutrition and hydration. The data were analysed thematically using Braun and
      Clarke's approach. RESULTS: Five themes were identified: pain, breathlessness,
      agitation, nutrition and hydration. The majority of responses related to symptoms
      that were sub-optimally managed, in particular pain. Nutrition and hydration were
      of significant concern, particularly for carers. Overall, respondents
      consistently asked about the most effective, evidence-based methods for managing
      symptoms and suggested areas where further research is necessary. CONCLUSIONS:
      This study highlights the perceptions and experiences of patients, families and
      professionals within palliative care, highlighting the need for improved care,
      communication and further research to establish which treatments are most
      effective within a palliative care population. This is essential to reduce harm
      and distress for patients and families.

PMID- 29656716
TI  - Assessing food security using household consumption expenditure surveys (HCES): a
      scoping literature review.
AB  - OBJECTIVE: To meet some of the UN's seventeen Sustainable Development Goals by
      2030, there is a need for more effective policy to reduce food insecurity in low
      income and lower-middle-income countries (LMIC). Measuring progress towards these
      goals requires reliable indicators of food security in these countries. Routinely
      conducted household consumption and expenditure surveys (HCES) provide
      potentially valuable and nationally representative data sets for this purpose.
      The present study aimed to assess methods used to determine national food
      security status using proxy measures from HCES data in LMIC globally. DESIGN: A
      scoping literature review was conducted using electronic databases. Of the 929
      abstracts identified, a total of twenty articles were reviewed against strict
      inclusion and exclusion criteria and included for further analysis. RESULTS:
      Fourteen LMIC globally were represented in the twenty articles. The simplest
      metric used to indicate food insecurity compared household food expenditure
      against a level of expenditure considered to be below the poverty line. Data on
      acquisition of food was commonly converted to available energy for the household
      using local food composition tables and expressed as a proportion of household
      total energy requirements. Dietary diversity was also assessed in some studies as
      well as experience of food insecurity. CONCLUSIONS: The review demonstrated that
      routinely collected HCES data sets provide a useful resource for the measurement
      of household food security in often resource-limited LMIC. Standardisation of
      methods used to assess food security is needed to allow for more useful
      comparisons between countries, as well as to assess temporal trends.

PMID- 29656715
TI  - Quantitative assessment of the association between IL-10 -592 A/C polymorphism
      and Kawasaki disease risk in Chinese population: evidence from a meta-analysis.
AB  - BACKGROUND: IL-10, as a proinflammatory and anti-inflammatory cytokine, has been
      thought to have an important role in the development of Kawasaki disease.
      Variation in the IL-10 gene might lead to altered protein production, which may
      result in Kawasaki disease. Several studies have been performed to investigate
      the IL-10 -592 A/C polymorphism and Kawasaki disease risk. Unfortunately, the
      results of previous studies were inconsistent. Therefore, we performed a meta
      analysis to derive a more precise estimation of the association between the IL-10
      -592 A/C polymorphism and Kawasaki disease risk. METHOD: The association between
      the IL-10 -592 A/C polymorphism and Kawasaki disease risk was assessed by odds
      ratios (ORs) together with their 95% confidence intervals (CIs). Six studies were
      enrolled in the present meta-analysis. RESULTS: Overall, no significant
      association between IL-10 -592 A/C polymorphism and Kawasaki disease risk was
      found under allele contrast (A versus C: OR=0.95, 95% CI=0.77-1.18, p=0.668),
      homozygote comparison (AA versus CC: OR=0.86, 95% CI=0.56-1.31, p=0.475),
      heterozygote comparison (CA versus CC: OR=0.88, 95% CI=0.65-1.19, p=0.479),
      recessive genetic model (AA versus CA/CC: OR=0.96, 95% CI=0.73-1.28, p=0.801), or
      dominant genetic model (AA/CA versus CC: OR=0.85, 95% CI=0.64-1.13, p=0.275).
      CONCLUSIONS: We conclude that IL-10 -592 A/C polymorphism was not associated with
      Kawasaki disease risk in the Chinese population. However, more primary large
      scale and well-designed studies are still required to further evaluate the
      interaction of IL-10 -592 A/C polymorphism with Kawasaki disease risk.

PMID- 29656717
TI  - Correlates of fruit and vegetable intake among parents and adolescents: findings
      from the Family Life, Activity, Sun, Health, and Eating (FLASHE) study.
AB  - OBJECTIVE: The present study aimed to examine the correlates of fruit and
      vegetable intake (FVI) separately among parents and their adolescents. DESIGN:
      Cross-sectional surveys. SETTING: Online survey. SUBJECTS: Parents and
      adolescents completed the Family Life, Activity, Sun, Health, and Eating (FLASHE)
      survey through the National Cancer Institute. The survey assessed daily intake
      frequencies of food/beverage groups, psychosocial, parenting and sociodemographic
      factors. Generalized linear models were run for both parents and adolescents, for
      a total of six models (three each): (i) sociodemographic characteristics; (ii)
      psychosocial factors; (iii) parent/caregiver factors. RESULTS: Parent
      participants (n 1542) were predominantly 35-59 years old (86 %), female (73 %),
      non-Hispanic White (71 %) or non-Hispanic Black (17 %), with household income
      <$US 100 000 (79 %). Adolescents (n 805) were aged 12-14 years (50 %), non
      Hispanic White (66 %) and non-Hispanic Black (15 %). Parents consumed 2.9 cups
      fruits and vegetables (F&V) daily, while adolescents consumed 2.2 cups daily.
      Educational attainment (higher education had greater FVI) and sex (men consumed
      more than women; all P<0.001) were significant FVI predictors. Parents with
      greater autonomous and controlled motivation, self-efficacy and preferences for
      fruit reported higher FVI (all P<0.001). Similarly, adolescents with greater
      autonomous and controlled motivation, self-efficacy and knowledge reported higher
      FVI (all P<0.001). Parenting factors of importance were co-deciding how many F&V
      teens should have, rules, having F&V in the home and cooking meals from scratch
      (all P<0.05). CONCLUSIONS: Findings suggest factors that impact FVI among parents
      and their adolescent(s), which highlight the importance of the role of parent
      behaviour and can inform tailored approaches for increasing FVI in various
      settings.

PMID- 29656719
TI  - Development of equations, based on milk intake, to predict starter feed intake of
      preweaned dairy calves.
AB  - There is a lack of studies that provide models or equations capable of predicting
      starter feed intake (SFI) for milk-fed dairy calves. Therefore, a multi-study
      analysis was conducted to identify variables that influence SFI, and to develop
      equations to predict SFI in milk-fed dairy calves up to 64 days of age. The
      database was composed of individual data of 176 calves from eight experiments,
      totaling 6426 daily observations of intake. The information collected from the
      studies were: birth BW (kg), SFI (kg/day), fluid milk or milk replacer intake
      (MI; l/day), sex (male or female), breed (Holstein or Holstein*Gyr crossbred) and
      age (days). Correlations between SFI and the quantitative variables MI, birth BW,
      metabolic birth BW, fat intake, CP intake, metabolizable energy intake, and age
      were calculated. Subsequently, data were graphed, and based on a visual appraisal
      of the pattern of the data, an exponential function was chosen. Data were
      evaluated using a meta-analysis approach to estimate fixed and random effects of
      the experiments using nonlinear mixed coefficient statistical models. A negative
      correlation between SFI and MI was observed (r=-0.39), but age was positively
      correlated with SFI (r=0.66). No effect of liquid feed source (milk or milk
      replacer) was observed in developing the equation. Two equations, significantly
      different for all parameters, were fit to predict SFI for calves that consume
      less than 5 (SFI5) l/day of milk or milk replacer: ${?rm SFI}_{{?,?lt?,5}}
      {?equals}0.1839_{{?,?pm?,0.0581}} {?times}{?rm MI}{?times}{?rm exp}^{{?left(
      {?left( {0.0333_{{?,?pm?,0.0021 }} {?minus}0.0040_{{?,?pm?,0.0011}} {?times}{?rm
      MI}} ?right){?times}?left( {{?rm A}{?minus}{?rm }?left( {0.8302_{{?,?pm?,0.5092}}
      {?plus}6.0332_{{?,?pm?,0.3583}} {?times}{?rm MI}} ?right)} ?right)} ?right)}}
      {?minus}?left( {0.12{?times}{?rm MI}} ?right)$ ; ${?rm SFI}_{{?,?gt?,5}}
      {?equals}0.1225_{{?,?pm?,0.0005 }} {?times}{?rm MI}{?times}{?rm exp}^{{?left(
      {?left( {0.0217_{{?,?pm?,0.0006 }} {?minus}0.0015_{{?,?pm?,0.0001}} {?times}{?rm
      MI}} ?right){?times}?left( {{?rm A}{?minus}?left( {3.5382_{{?,?pm?,1.3140 }}
      {?plus}1.9508_{{?,?pm?,0.1710}} {?times}{?rm MI}} ?right)} ?right)} ?right)}}
      {?minus}?left( {0.12{?times}{?rm MI}} ?right)$ where MI is the milk or milk
      replacer intake (l/day) and A the age (days). Cross-validation and bootstrap
      analyses demonstrated that these equations had high accuracy and moderate
      precision. In conclusion, the use of milk or milk replacer as liquid feed did not
      affect SFI, or development of SFI over time, which increased exponentially with
      calf age. Because SFI of calves receiving more than 5 l/day of milk/milk replacer
      had a different pattern over time than those receiving <5 l/day, separate
      prediction equations are recommended.

PMID- 29656720
TI  - The Risk of Cross Infection in the Emergency Department: A Simulation Study.
AB  - OBJECTIVESThe risk of cross infection in a busy emergency department (ED) is a
      serious public health concern, especially in times of pandemic threats. We
      simulated cross infections due to respiratory diseases spread by large droplets
      using empirical data on contacts (ie, close-proximity interactions of <=1m) in an
      ED to quantify risks due to contact and to examine factors with differential
      risks associated with them.DESIGNProspective study.PARTICIPANTSHealth workers
      (HCWs) and patients.SETTINGA busy ED.METHODSData on contacts between participants
      were collected over 6 months by observing two 12-hour shifts per week using a
      radiofrequency identification proximity detection system. We simulated cross
      infection due to a novel agent across these contacts to determine risks
      associated with HCW role, chief complaint category, arrival mode, and ED
      disposition status.RESULTSCross-infection risk between HCWs was substantially
      greater than between patients or between patients and HCWs. Providers had the
      least risk, followed by nurses, and nonpatient care staff had the most risk.
      There were no differences by patient chief complaint category. We detected
      differential risk patterns by arrival mode and by HCW role. Although no
      differential risk was associated with ED disposition status, 0.1 infections were
      expected per shift among patients admitted to hospital.CONCLUSIONThese
      simulations demonstrate that, on average, 11 patients who were infected in the ED
      will be admitted to the hospital over the course of an 8-week local influenza
      outbreak. These patients are a source of further cross-infection risk once in the
      hospital.Infect Control Hosp Epidemiol 2018;39:688-693.

PMID- 29656714
TI  - Epidemiology of sepsis in intensive care units in Turkey: a multicenter, point
      prevalence study.
AB  - BACKGROUND: The prevalence and mortality of sepsis are largely unknown in Turkey,
      a country with high antibiotic resistance. A national, multicenter, point
      prevalence study was conducted to determine the prevalence, causative
      microorganisms, and outcome of sepsis in intensive care units (ICUs) in Turkey.
      METHODS: A total of 132 ICUs from 94 hospitals participated. All patients (aged >
      18 years) present at the participating ICUs or admitted for any duration within a
      24-h period (08:00 on January 27, 2016 to 08:00 on January 28, 2016) were
      included. The presence of systemic inflammatory response syndrome (SIRS), severe
      sepsis, and septic shock were assessed and documented based on the consensus
      criteria of the American College of Chest Physicians and Society of Critical Care
      Medicine (SEPSIS-I) in infected patients. Patients with septic shock were also
      assessed using the SEPSIS-III definitions. Data regarding demographics, illness
      severity, comorbidities, microbiology, therapies, length of stay, and outcomes
      (dead/alive during 30 days) were recorded. RESULTS: Of the 1499 patients included
      in the analysis, 237 (15.8%) had infection without SIRS, 163 (10.8%) had
      infection with SIRS, 260 (17.3%) had severe sepsis without shock, and 203 (13.5%)
      had septic shock. The mortality rates were higher in patients with severe sepsis
      (55.7%) and septic shock (70.4%) than those with infection alone (24.8%) and
      infection + SIRS (31.2%) (p < 0.001). According to SEPSIS-III, 104 (6.9%)
      patients had septic shock (mortality rate, 75.9%). The respiratory system (71.6%)
      was the most common site of infection, and Acinetobacter spp. (33.7%) were the
      most common isolated pathogen. Approximately, 74.9%, 39.1%, and 26.5% of
      Acinetobacter, Klebsiella, and Pseudomonas spp. isolates, respectively, were
      carbapenem-resistant, which was not associated with a higher mortality risk. Age,
      acute physiology and chronic health evaluation II score at ICU admission,
      sequential organ failure assessment score on study day, solid organ malignancy,
      presence of severe sepsis or shock, Candida spp. infection, renal replacement
      treatment, and a nurse-to-patient ratio of 1:4 (compared with a nurse-to-patient
      ratio of 1:2) were independent predictors of mortality in infected patients.
      CONCLUSIONS: A high prevalence of sepsis and an unacceptably high mortality rate
      were observed in Turkish ICUs. Although the prevalence of carbapenem resistance
      was high in Turkish ICUs, it was not associated with a higher risk for mortality.
      TRIAL REGISTRATION: ClinicalTrials.gov ID NCT03249246 . Date: August 15, 2017.
      Retrospectively registered.

PMID- 29656718
TI  - The Pediatric Heart Network Scholar Award programme: a unique mentored award
      embedded within a multicentre network.
AB  - BACKGROUND: The Pediatric Heart Network designed a career development award to
      train the next generation of clinician scientists in paediatric-cardiology
      related research, a historically underfunded area. We sought to identify the
      strengths/weaknesses of the programme and describe the scholars' academic
      achievements and the network's return on investment. METHODS: Survey questions
      designed to evaluate the programme were sent to applicants - 13 funded and 19
      unfunded applicants - and 20 mentors and/or principal investigators. Response
      distributions were calculated. chi2 tests of association assessed differences in
      ratings of the application/selection processes among funded scholars, unfunded
      applicants, and mentors/principal investigators. Scholars reported post-funding
      academic achievements. RESULTS: Survey response rates were 88% for applicants and
      100% for mentor/principal investigators. Clarity and fairness of the review were
      rated as "clear/fair" or "very clear/very fair" by 98% of respondents, but the
      responses varied among funded scholars, unfunded applicants, and
      mentors/principal investigators (clarity chi2=10.85, p=0.03; fairness chi2=16.97,
      p=0.002). Nearly half of the unfunded applicants rated feedback as "not useful"
      (47%). "Expanding their collaborative network" and "increasing publication
      potential" were the highest-rated benefits for scholars. Mentors/principal
      investigators found the programme "very" valuable for the scholars (100%) and the
      network (75%). The 13 scholars were first/senior authors for 97 abstracts and 109
      manuscripts, served on 22 Pediatric Heart Network committees, and were awarded
      $9,673,660 in subsequent extramural funding for a return of ~$10 for every
      scholar dollar spent. CONCLUSIONS: Overall, patient satisfaction with the Scholar
      Award was high and scholars met many academic markers of success. Despite this,
      programme challenges were identified and improvement strategies were developed.

PMID- 29656721
TI  - Radiofrequency catheter ablation for ventricular tachycardia in ischaemic
      cardiomyopathy due to Kawasaki disease.
AB  - In some patients with Kawasaki disease, a prior myocardial infarction causes
      ventricular tachycardia in the chronic post-myocardial infarction phase. We
      report the case of a 41-year-old man with symptomatic and haemodynamically
      unstable ventricular tachycardia in whom substrate ablation was performed for the
      ventricular tachycardia before insertion of an implantable cardioverter
      defibrillator.

PMID- 29656723
TI  - Gastroenteritis outbreak at a health function caused by an emerging recombinant
      strain of Norovirus GII.P16/GII.4 Sydney 2012, Australia.
AB  - An emerging recombinant norovirus GII.P16/GII.4 Sydney 2012 strain caused a
      gastroenteritis outbreak amongst attendees at a large health function in regional
      New South Wales, Australia. This was the third outbreak caused by the recombinant
      GII.P16/GII.4 Sydney 2012 strain in this region in 2017, which appears to be
      emerging as a common strain in the Hunter New England region.

PMID- 29656722
TI  - TOWARD A CONTINGENCY MODEL FOR HOSPITAL-BASED HEALTH TECHNOLOGY ASSESSMENT:
      EVIDENCE FROM ADHOPHTA PROJECT.
AB  - OBJECTIVES: Hospital-based health technology assessment (HB-HTA) is becoming
      increasingly relevant because of its role in managing the introduction and
      withdrawal of health technologies. The organizational arrangement in which HB-HTA
      activities are conducted depends on several contextual factors, although the
      dominant models have several similarities. The aims of this study were to
      explore, describe, interpret, and explain seven cases of the application of HB
      HTA logic and to propose a classification for HB-HTA organizational models which
      may be beneficial for policy makers and HTA professionals. METHODS: The study was
      part of the AdHopHTA Project, granted under the European 7th Framework Research
      Programme. A case study methodology was applied to analyze seven HB-HTA
      initiatives in seven countries, with collection of qualitative and quantitative
      data. Cross-case analysis was performed within the framework of contingent
      organizational theory. RESULTS: Evidence showed that some organizational or
      "structural" variables, namely the level of procedure formalization/structuration
      and the level of integration with other HTA bodies at the national, regional, and
      provincial levels, predominantly shape the HB-HTA approach, determining a
      contingency model of HB-HTA. Crossing the two variables, four options have
      emerged: integrated specialized HTA unit, stand-alone HTA unit, integrated
      essential HTA, independent group unit. CONCLUSIONS: No one-best-way approach can
      be used for HTA at the hospital level. Rather, the characteristics of HTA models
      depend on many contextual factors. Such conceptualization may aid the diffusion
      of HB-HTA to inform managerial decision making and clinical practice.

PMID- 29656724
TI  - Large right ventricular sinusoids in an infant with aorta-left ventricular tunnel
      and proximal right coronary artery atresia.
AB  - We report a 1-month-old infant diagnosed with an aorta-left ventricular tunnel,
      ventricular septal defect, and right coronary atresia with right ventricular
      sinusoids. The patient's anatomy and physiology did not indicate right
      ventricular-dependent coronary circulation, and therefore right ventricular
      decompression could be performed without compromising coronary perfusion during
      surgical correction. A detailed understanding of the coronary anatomy is critical
      in managing this defect when coronary anomalies are present.

PMID- 29656725
TI  - Force of infection of Helicobacter pylori in Mexico: evidence from a national
      survey using a hierarchical Bayesian model.
AB  - Helicobacter pylori (H. pylori) is present in the stomach of half of the world's
      population. The force of infection describes the rate at which susceptibles
      acquire infection. In this article, we estimated the age-specific force of
      infection of H. pylori in Mexico. Data came from a national H. pylori
      seroepidemiology survey collected in Mexico in 1987-88. We modelled the number of
      individuals with H. pylori at a given age as a binomial random variable. We
      assumed that the cumulative risk of infection by a given age follows a modified
      exponential catalytic model, allowing some fraction of the population to remain
      uninfected. The cumulative risk of infection was modelled for each state in
      Mexico and were shrunk towards the overall national cumulative risk curve using
      Bayesian hierarchical models. The proportion of the population that can be
      infected (i.e. susceptible population) is 85.9% (95% credible interval (CR) 84.3%
      87.5%). The constant rate of infection per year of age among the susceptible
      population is 0.092 (95% CR 0.084-0.100). The estimated force of infection was
      highest at birth 0.079 (95% CR 0.071-0.087) decreasing to zero as age increases.
      This Bayesian hierarchical model allows stable estimation of state-specific force
      of infection by pooling information between the states, resulting in more
      realistic estimates.

PMID- 29656726
TI  - The mental health consumer movement and peer providers in Israel.
AB  - Self-help peer-support groups in Israel emerged in the 1980s and, over time,
      dynamically interacted and co-developed with the statutory mental health (MH)
      system. In this editorial, I outline historical milestones of how the evolution
      of the Israeli mental health system was influenced by the consumer movement. A
      brief depiction of the consumer movement history. At first, consumers operated
      outside of the mainstream MH system. Gradually, consumer groups and institutional
      personnel joined efforts towards community integration and enhancement of quality
      of life, pushing forward a person-centered recovery orientation. In turn, some
      administrators and key stakeholders in rehabilitation community services grew to
      value the impact of knowledge-by-experience in contemporary mental health care.
      In this context, over the past decade, peer roles were developed in the mental
      health system, including consumer-providers in community services and peer
      specialists in inpatient psychiatric hospitals. The insertion of peer roles into
      the mainstream MH system is far-reaching, including the placement of a peer
      project coordinator within the ministry of health. I describe the unique
      contribution of peers, as experts-by-experience, to mainstream professional
      knowledge and practice. I also highlight the potential challenges involved when
      peer models of care are added to traditional medical models of care. The Israeli
      case demonstrates how the consumer movement can play an active role in MH systems
      and be acknowledged and recognised as a partner for changing policy, practice and
      reshaping formal institutions. In addition, they play a vital role in the
      development of peer-support services.

PMID- 29656727
TI  - Outcomes in Hospitalized Ischemic Stroke Patients with Dementia on Admission: A
      Population-Based Cohort Study.
AB  - BACKGROUND: Dementia prevalence is rising, and it will double in the next 20
      years. This study sought to understand the prevalence of dementia in hospitalized
      patients with ischemic stroke, and its impact on outcomes. METHODS: Using the
      Canadian Institute of Health Information's (CIHI) Discharge Abstract Database
      (DAD), all acute ischemic stroke admissions from April 2003 to March 2015 in
      Canada (excluding Quebec) were analyzed. Concurrent dementia at the time of
      admission was assessed based on hospital diagnostic codes. Characteristics and in
      hospital outcomes were compared in patients with and without dementia using chi 2
      and negative binomial, as well as Poisson regression analysis. RESULTS: During
      the observed period, 313,138 people were admitted to a hospital in Canada for an
      ischemic stroke. Of those, 21,788 (7.0%) had a concurrent diagnosis of dementia.
      People with dementia had older median age (84 vs. 76 years; p<0.0001), were more
      often female (59.6% vs. 48.4%; p<0.0001) and more often had Charlson-Deyo
      Comorbidity Index >=2 (64.5% vs. 43.5%; p<0.0001). Patients with dementia were
      less likely to be discharged to a rehabilitation facility (adjusted risk ratio
      [RR] 3.089, 95% confidence interval [CI] 2.992-3.188, p<0.0001) or home
      independently (adjusted RR 0.756, 95% CI 0.737-0.776,
      p<0.0001).InterpretationApproximately 1 in 13 hospitalized ischemic stroke
      patients has coded dementia. Patients with ischemic stroke and concurrent
      dementia have higher mortality, face significantly more dependence after stroke
      and utilize greater healthcare resources than stroke patients without dementia.
      Causative conclusions are limited by the administrative data source. Early care
      planning and coordination could potentially optimize outcomes.

PMID- 29656728
TI  - Relationship between mean platelet volume-to-lymphocyte ratio and coronary artery
      abnormalities in Kawasaki disease.
AB  - OBJECTIVES: Recently, mean platelet volume-to-lymphocyte ratio has emerged as a
      novel parameter of inflammation. No study has investigated the role of mean
      platelet volume-to-lymphocyte ratio in children with Kawasaki disease. We aimed
      to evaluate the relationship between mean platelet volume-to-lymphocyte ratio and
      coronary artery abnormalities in Kawasaki disease. METHODS: Between January 2008
      and January 2017, a total of 58 children with Kawasaki disease and 42 healthy
      subjects matched for sex and age were enrolled. Before the treatment,
      transthoracic echocardiography for all children was performed. Clinical and
      laboratory results including mean platelet volume, platelet distribution width,
      red blood cell distribution width, and counts of platelets, neutrophils,
      lymphocytes, and white blood cells, erythrocyte sedimentation rate, and C
      reactive protein levels were measured. Mean platelet volume-to-lymphocyte ratio
      was calculated as mean platelet volume divided by lymphocyte count. RESULTS:
      Compared with healthy controls, mean platelet volume-to-lymphocyte ratio was
      significantly lower in the children with Kawasaki disease (p<0.01). A total of 14
      patients (24.1%) had incomplete Kawasaki disease and 15 (25.8%) children with
      Kawasaki disease had coronary involvement. Mean platelet volume-to-lymphocyte
      ratio was significantly lower in patients with coronary artery abnormalities
      (p<0.01). According to receiver operating characteristic curve analysis performed
      for the prediction of coronary artery abnormalities, the best cut-off point for
      mean platelet volume-to-lymphocyte ratio was 2.5 (area under curve=0.593,
      sensitivity 53.3%, specificity 51.1%). CONCLUSION: It was first shown that the
      children with Kawasaki disease have lower mean platelet volume-to-lymphocyte
      ratio compared with control subjects. Mean platelet volume-to-lymphocyte ratio
      may be helpful in predicting coronary artery lesions in patients with Kawasaki
      disease.

PMID- 29656729
TI  - 'False-positive' self-reported psychotic experiences in the general population:
      an investigation of outcome, predictive factors and clinical relevance.
AB  - AIMS: Self-reported psychotic experiences (SRPE) by individuals from the general
      population are often unconfirmed by clinical interview and referred to as 'false
      positive' (FP) SRPE. FP SRPE have been suggested to represent the mildest form of
      risk along the extended psychosis continuum. However, little is known about their
      (clinical) outcome and evolution over time. Aims of this study were to
      prospectively examine, in individuals with FP SRPE, (1) the prevalence of
      remission, persistence and transition to validated PE at 3-year follow-up; (2)
      potential baseline psychopathological and psychosocial predictors of persistence
      of FP SRPE and transition to validated PE; and (3) whether those with persistent
      FP SRPE and validated PE already differed on psychopathology and psychosocial
      factors at baseline. We tested the hypotheses that (i) individuals with FP SRPE
      would be more likely to have SRPE and validated PE at follow-up; and (ii) that FP
      SRPE would be predictive of lower functioning and more psychopathology and help
      seeking behaviour at follow-up. METHODS: Baseline (n = 6646) and 3-year follow-up
      (n = 5303) data of the second the Netherlands Mental Health Survey and Incidence
      Study (NEMESIS-2), a general population research project on prevalence,
      incidence, course and consequences of psychiatric disorders was used. Self-report
      of PE was followed by clinical interview to determine clinical validity. The
      presence of mood, anxiety and substance use disorders, childhood adversity, help
      seeking and functioning as well as PE characteristics (number, frequency,
      distress and impact) were used in the analyses which included only individuals
      with complete data for both assessments waves (n = 4683). RESULTS: At baseline,
      454 participants had any FP SRPE; of these 372 participants had complete follow
      up data available. Those with baseline FP SRPE were significantly more likely to
      report SRPE (OR = 3.58; 95% CI 2.38-5.40, p < 0.001) and validated PE (OR = 6.26;
      95% CI 3.91-10.02, p < 0.001) at follow-up. Baseline FP SRPE also predicted the
      presence of mood and anxiety disorders, reduced functioning and help-seeking at
      follow-up. Several baseline psychopathological, psychosocial and PE
      characteristics were predictive for the persistence of SRPE. These factors also
      differentiated groups with FP SRPE or validated PE from those with remitted FP
      SRPE at follow-up.Conclusions.'FP SRPE' are not truly 'false' as they index risk
      for the development of clinically relevant psychotic symptoms, development of
      mood and anxiety disorders and reduced functioning. Self-reported PE, even
      unconfirmed, warrant 'watchful waiting' and follow-up over time, especially when
      they are reported by individuals with reduced psychosocial functioning and
      general psychiatric problems.

PMID- 29656730
TI  - EXPLORING MEDICAL DEVICES: THE USE OF RISK ASSESSMENT TOOLS AND THEIR LINK WITH
      TRAINING IN HOSPITALS.
AB  - OBJECTIVES: The aim of this study was to explore the risk assessment tools and
      criteria used to assess the risk of medical devices in hospitals, and to explore
      the link between the risk of a medical device and how those risks impact or alter
      the training of staff. METHODS: Within a broader questionnaire on implementation
      of a national guideline, we collected quantitative data regarding the types of
      risk assessment tools used in hospitals and the training of healthcare staff.
      RESULTS: The response rate for the questionnaire was 81 percent; a total of sixty
      five of eighty Dutch hospitals. All hospitals use a risk assessment tool and the
      biggest cluster (40 percent) use a tool developed internally. The criteria used
      to assess risk most often are: the function of the device (92 percent), the
      severity of adverse events (88 percent) and the frequency of use (77 percent).
      Forty-seven of fifty-six hospitals (84 percent) base their training on the risk
      associated with a medical device. For medium- and high-risk devices, the main
      method is practical training. As risk increases, the amount and type of training
      and examination increases. CONCLUSIONS: Dutch hospitals use a wide range of tools
      to assess the risk of medical devices. These tools are often based on the same
      criteria: the function of the device, the potential severity of adverse events,
      and the frequency of use. Furthermore, these tools are used to determine the
      amount and type of training required for staff. If the risk of a device is
      higher, then the training and examination is more extensive.

PMID- 29656732
TI  - The role of community mental health services in supporting oral health outcomes
      among consumers.
AB  - People with a lived experience of mental illness are at a higher risk for
      developing oral diseases and having poorer oral health than the broader
      population. This paper explores the role of Australian community mental health
      services in supporting the prevention and management of poor oral health among
      people living with mental illness. Through focus groups and semi-structured
      interviews, participants identified the value of receiving oral health support
      within a community mental health setting, in particular the delivery of basic
      education, preventive strategies, assistance with making or attending
      appointments and obtaining priority access to oral health services. Engagement
      with Community Health Services and referrals generated through the priority
      access system were identified as key enablers to addressing oral health issues.
      This study provides new insight into the importance of undertaking an integrated
      approach to reducing the oral health disparities experienced by those living with
      mental illness.

PMID- 29656733
TI  - Hope and foresight for your patients with ALS.

PMID- 29656731
TI  - Validity of an FFQ to measure nutrient and food intakes in Tanzania.
AB  - OBJECTIVE: FFQ are often used to estimate food and nutrient intakes to rank
      individuals by their level of intake. We evaluated the relative validity of a
      semi-quantitative FFQ created for use in Tanzania by comparing it with two 24 h
      diet recalls. DESIGN: We measured relative validity of the FFQ with deattenuated
      energy-adjusted rank correlations for nutrients, deattenuated rank correlations
      for food groups, and performed a cross-classification analysis of energy-adjusted
      nutrient quartiles using percentage of agreement and Bland-Altman analysis.
      SETTING: Interviews were conducted in 2014 in participants' homes in Ukonga, Dar
      es Salaam, Tanzania. SUBJECTS: We surveyed 317 adults aged 40 years or older from
      the general public. RESULTS: Deattenuated energy-adjusted rank correlation
      coefficients of nutrients ranged from -0.03 for riboflavin to 0.41 for percentage
      of energy from carbohydrates, with a median correlation of 0.21. Coefficients for
      food groups ranged from 0.00 for root vegetables to 0.51 for alcohol, with a
      median of 0.35. Relative to the average of the two 24 h diet recalls, the FFQ
      overestimated energy intake and intakes of all nutrients and food groups, other
      than tea, with ratios among nutrients ranging from 1.34 for SFA to 7.08 for
      vitamin A; and among food groups from 0.92 for tea to 9.00 for fruit. The
      percentage of participants classified into the same nutrient intake quartile
      ranged from 23 % for SFA to 32 % for both niacin and pantothenic acid, with a
      median of 28 %. CONCLUSIONS: The FFQ performed moderately well in urban Tanzanian
      adults.

PMID- 29656734
TI  - Prediction to prevention in Alzheimer's disease and dementia.

PMID- 29656735
TI  - Evidence-based care in Duchenne muscular dystrophy.

PMID- 29656736
TI  - Understanding risk of PML through multiple sclerosis.

PMID- 29656737
TI  - Intravenous versus subcutaneous immunoglobulin.

PMID- 29656739
TI  - Classification of epilepsies in the 18th century.

PMID- 29656740
TI  - Sven van der Lee.

PMID- 29656741
TI  - Impairment of creativity by anaesthesia.

PMID- 29656738
TI  - Intravenous versus subcutaneous immunoglobulin - Authors' reply.

PMID- 29656742
TI  - Pathogenesis of progressive multifocal leukoencephalopathy and risks associated
      with treatments for multiple sclerosis: a decade of lessons learned.
AB  - Progressive multifocal leukoencephalopathy (PML) is a rare, devastating
      demyelinating disease of the CNS caused by the JC virus (JCV) that occurs in
      patients with compromised immune systems. Detection of PML in systemically
      immunocompetent patients with multiple sclerosis treated with natalizumab points
      to a role for this drug in the pathophysiology of PML. Emerging knowledge of the
      cellular and molecular biology of JCV infection and the pathogenesis of PML
      including interplay of this common virus with the human immune system and
      features of natalizumab that might contribute to PML pathogenesis-provides new
      opportunities to monitor viral status and predict risk of JCV-associated disease.
      In the absence of an effective treatment for PML, early detection of the disease
      in patients with multiple sclerosis who are receiving natalizumab or other
      immunomodulatory treatments is vital to minimize CNS injury and avoid severe
      disability. Frequent MRI, stratified along a clinical and virus-specific immune
      risk profile, can be used to detect presymptomatic PML. Improved approaches to
      PML risk stratification are needed to guide treatment choices and surveillance of
      patients with multiple sclerosis.

PMID- 29656743
TI  - Prognostic stratification model for patients with stage I non-small cell lung
      cancer adenocarcinoma treated with surgical resection without adjuvant therapies
      using metabolic features measured on F-18 FDG PET and postoperative pathologic
      factors.
AB  - PURPOSE: In the management of non-small cell lung cancer (NSCLC), the prognostic
      stratification of stage I tumors without indication of adjuvant therapy, remains
      to be elucidated in order to better select patients who can benefit from
      additional therapies. We aimed to stratify the prognosis of patients with stage I
      NSCLC adenocarcinoma using clinicopathologic factors and F-18 FDG PET. MATERIALS
      AND METHODS: We retrospectively enrolled 128 patients with stage I NSCLC without
      any high-risk factors, who underwent curative surgical resection without adjuvant
      therapies. Preoperative clinical and postoperative pathologic factors were
      evaluated by medical record review. Standardized uptake value corrected with lean
      body mass (SULmax) was measured on F-18 FDG PET. Among the factors, independent
      predictors for recurrence-free survival (RFS) were selected using univariate and
      stepwise multivariate survival analyses. A prognostic stratification model for
      RFS was designed using the selected factors. RESULTS: Tumors recurred in nineteen
      patients (14.8%). Among the investigated clinicopathologic and FDG PET factors,
      SULmax on PET and spread through air spaces (STAS) on pathologic review were
      determined to be independent prognostic factors for RFS. A prognostic model was
      designed using these two factors in the following manner: (1) Low-risk: SULmax <=
      1.9 and no STAS, (2) intermediate-risk: neither low-risk nor high-risk, (3) high
      risk: SULmax>1.9 and observed STAS. This model exhibited significant predictive
      power for RFS. CONCLUSION: We showed that FDG uptake and STAS are significant
      prognostic markers in stage I NSCLC adenocarcinoma treated with surgical
      resection without adjuvant therapies.

PMID- 29656744
TI  - Economic impact of preventing brain metastases with alectinib in ALK-positive non
      small cell lung cancer.
AB  - OBJECTIVES: Despite improved progression-free survival, most patients treated
      with the first generation ALK inhibitor crizotinib ultimately experience central
      nervous system (CNS) progression. Brain metastases (BM) are associated with high
      clinical burden in patients with advanced anaplastic lymphoma kinase positive
      (ALK+) non-small cell lung cancer (NSCLC). In this study we estimate the real
      world economic burden of BM in newly diagnosed ALK+ NSCLC patients and
      investigate whether alectinib, a second generation ALK inhibitor that delays CNS
      progression, may help reduce healthcare costs in patients with ALK+ NSCLC.
      MATERIALS AND METHODS: Cost of BM was measured in ALK+ NSCLC patients identified
      from a stacked PharMetrics Plus and MarketScan claims database from January 2008
      to March 2016 and December 2015, respectively. Per patient per month (PPPM) cost
      of BM was calculated as the difference in baseline-adjusted total costs in
      patients with and without BM over a variable follow-up period of up to 24 months.
      Cumulative incidence of new BM was derived from 88 alectinib-treated and 93
      crizotinib-treated patients without baseline BM in a randomized phase III
      clinical trial, ALEX (NCT02075840). Costs of BM per patient were then calculated
      by applying the PPPM BM cost to the number of incident BM patients in each
      treatment cohort. RESULTS: 207 patients with no BM and 198 with BM were selected
      from the claims database. Total cost of BM was estimated at $6,029 PPPM. 24-month
      cumulative incidence rates of BM from the clinical trial were 7.2% and 45.3% for
      alectinib and crizotinib, respectively. Over follow-up, alectinib was estimated
      to reduce BM-related costs by $41,434 per patient compared to crizotinib.
      CONCLUSION: BM is associated with substantial economic burden. Alectinib was
      estimated to reduce BM-related costs by preventing or delaying the occurrence of
      BM compared to crizotinib.

PMID- 29656745
TI  - Severe adverse events impact overall survival and costs in elderly patients with
      advanced non-small cell lung cancer on second-line therapy.
AB  - OBJECTIVES: Elderly patients with advanced non-small lung cancer (aNSCLC)
      represent a high-risk patient population due to disease burden, comorbidities,
      and performance status, particularly after progressing on first-line therapy.
      Among elderly patients who receive second-line therapy, treatment related
      toxicities can have substantial impact on both clinical and economic outcomes.
      This study assessed the impact of severe adverse events (AEs) during second-line
      therapy on overall survival (OS) and all-cause heathcare costs in elderly with
      aNSCLC. MATERIALS AND METHODS: Patients with aNSCLC aged >=65 years who initiated
      second-line chemotherapy/targeted therapy were identified in the SEER-Medicare
      database (2007-2011). Fifty-seven AEs were identified by literature review and
      consultation with two oncologists. Severe AEs were defined as AEs that required a
      hospitalization and were operationalized based on AE diagnosis(es) recorded
      during hospitalizations. OS post-second-line initiation and healthcare costs
      during second-line were compared between patients with and without severe AEs.
      RESULTS: Among 3967 patients initiating second-line therapy, 1624 (41%) had >=1
      severe AE, where hypertension (26%), anemia (24%), and pneumonia (23%) were most
      commonly reported. Patients with and without severe AEs had similar demographic
      and cancer characteristics at diagnosis and similar second-line treatment
      regimens, but patients with severe AEs had more comorbidities at second-line
      initiation. Median OS was lower in patients with versus without severe AEs (6 vs.
      11 months). After multivariate adjustment, hazard of death was more than twice
      higher in patients with versus without severe AEs (adjusted hazard ratio [HR]
      2.31, 95% CI 2.16-2.47). Healthcare costs were more than twice higher in patients
      with versus without severe AEs ($16,135 vs. $7559 per-patient-per-month).
      CONCLUSION: Severe AEs among elderly patients with aNSCLC treated with second
      line chemotherapy/targeted therapy were found to be associated with decreased OS
      and increased healthcare costs. Results suggest a potential link between severe
      AEs in second-line treated aNSCLC elderly and patient survival and economic
      burden to the healthcare system.

PMID- 29656746
TI  - Impacts of EGFR-mutation status and EGFR-TKI on the efficacy of stereotactic
      radiosurgery for brain metastases from non-small cell lung adenocarcinoma: A
      retrospective analysis of 133 consecutive patients.
AB  - OBJECTIVES: Recent advances in target therapies have prolonged overall survival
      (OS) for patients with epidermal growth factor receptor (EGFR)-mutant lung
      cancer. The impact of EGFR mutations on stereotactic radiosurgery (SRS) for brain
      metastases (BM) has yet to be determined. The present study sought to evaluate
      the efficacy and limitations of SRS, administered with EGFR-tyrosine kinase
      inhibitors (TKI), for BM from EGFR-mutant lung adenocarcinoma. MATERIALS AND
      METHODS: This retrospective observational study analyzed data from patients with
      BM arising from EGFR-mutant lung adenocarcinoma who received upfront Gamma Knife
      SRS between December 2010 and April 2016. OS and distant and local intracranial
      disease control rates were calculated. The prognostic factors for each event were
      also determined. RESULTS: One hundred thirty-three consecutive patients (47
      males/86 females) were eligible. The median age was 69 years, and the median
      Karnofsky performance status (KPS) was 90. Sixty-six patients (50%) had no
      history of EGFR-TKI use at the time of SRS. EGFR-TKI were administered to 85% of
      EGFR-TKI naive patients after SRS. One- and 2-year OS rates were 74% and 52%,
      respectively. One- and 2-year distant BM recurrence rates (per patient) after SRS
      were 34% and 53%, respectively. One- and 2-year rates of local tumor control (per
      lesion) were 97% and 95%, respectively. Multivariate proportional hazards
      analyses showed that being EGFR-TKI naive was associated with longer OS (HR:
      0.42, P < 0.001), a lower distant intracranial recurrence rate (HR: 0.61, P =
      0.037) and a higher local tumor control rate (HR: 0.28, P = 0.001). CONCLUSIONS:
      The present study demonstrated the upfront SRS strategy to offer a minimally
      invasive and effective treatment option for EGFR-mutant lung adenocarcinoma
      patients with limited BM. EGFR-TKI naive patients were found to be a distinct
      subgroup for which a longer survival time and durable intracranial disease
      control can be expected.

PMID- 29656747
TI  - Efficacy and safety of nivolumab in previously treated patients with non-small
      cell lung cancer: A multicenter retrospective cohort study.
AB  - INTRODUCTION: Nivolumab has been shown to be effective and safe in previously
      treated patients with advanced non-small cell lung cancer (NSCLC). However,
      little is known regarding its performance in real-world (i.e., non-trial)
      settings. Furthermore, nivolumab efficacy is unknown in patients who are
      ineligible for clinical trials or who are categorized into small subgroups in
      such trials. METHODS: We conducted a 15-center, observational, retrospective
      cohort study of patients with advanced NSCLC who received nivolumab monotherapy
      between January and December 2016. RESULTS: Of 613 patients included in our
      study, 141 had poor performance status (PS) and 106 were EGFR mutation - or ALK
      rearrangement-positive. The response and disease control rates were 20% and 44%,
      respectively; the estimated 1-year progression-free survival (PFS) was 18%.
      Multivariate analysis identified never smoking, poor PS, and EGFR mutation/ALK
      rearrangement as independent negative predictors of PFS. The most frequently
      reported grade >=3 adverse event was pneumonitis (5% of patients). Severe
      pneumonitis (grade >=3) occurred significantly earlier than mild pneumonitis (1.6
      vs. 2.3 months, P = 0.031). Patients with pneumonitis achieved higher response
      rates and longer PFS than those without (37% vs. 18%, and 5.8 vs. 2.1 months,
      respectively; P = 0.002). CONCLUSIONS: Smoking status, PS, and EGFR mutation/ALK
      rearrangement were independent predictors of PFS. Our study elucidated
      nivolumab's efficacy in previously underreported patient populations; i.e., those
      with poor PS and/or with driver oncogenes. We also found that pneumonitis is not
      infrequent, and carries key implications for outcomes. These data should be
      useful for improving the clinical courses of nivolumab-treated patients with
      NSCLC.

PMID- 29656748
TI  - Nivolumab-induced severe pancytopenia in a patient with lung adenocarcinoma.
AB  - Severe leukopenia, thrombocytopenia, and bi-cytopenia due to nivolumab have been
      reported. In this report, we present the first case of nivolumab-induced severe
      pancytopenia in a patient with lung adenocarcinoma. A 56-year-old Japanese man
      with lung adenocarcinoma received nivolumab therapy as second-line treatment.
      After 3 cycles of this therapy, although computed tomography (CT) showed a
      reduced tumor size, laboratory findings revealed pancytopenia and a bone marrow
      biopsy showed a severely hypoplastic marrow. The pancytopenia was diagnosed as an
      adverse effect of nivolumab; filgrastim (75 MUg/day), steroid-pulse therapy
      (intravenous methylprednisolone: 500 mg/day), and subsequently intravenous
      prednisolone (50 mg/day) were administered. Furthermore, intravenous
      administration of immunoglobulins was also performed. However, these treatments
      were ineffective. He was further diagnosed with fungal pneumonia and a catheter
      related bloodstream infection. Anti-bacterial chemotherapy was administered. Two
      months after hospitalization, the neutrophil count improved to 1000/MUL, but
      multiple red blood cell and platelet transfusions were needed. Therefore, further
      chemotherapy for lung adenocarcinoma could not be initiated, and the patient died
      due to progression of lung cancer 118 days after the onset of pancytopenia. The
      possibility of severe pancytopenia as an immune-related adverse event should be
      considered as a mandatory prerequisite for nivolumab therapy.

PMID- 29656749
TI  - Tumor associated macrophages support the growth of FGF9-induced lung
      adenocarcinoma by multiple mechanisms.
AB  - OBJECTIVES: Tumor-associated macrophages (TAMs) are known to promote
      tumorigenesis but the mechanism(s) remain elusive. We have developed a mouse
      model of lung cancer that is initiated through an inducible overexpression of
      fibroblast growth factor 9 (FGF9) in type-2 pneumocytes. Expression of FGF9 in
      adult lungs resulted in a rapid development of multiple adenocarcinoma-like tumor
      nodules, and is associated with an intense immunological reaction. The purpose of
      this study is to characterize the immune response to the FGF9-induced lung
      adenocarcinoma and to determine the contribution of TAMs to growth and survival
      of these tumors. MATERIALS AND METHODS: We used flow cytometry, immunostaining,
      RT-PCR and in vitro culture system on various cell populations isolated from the
      FGF9-induced adenocarcinoma mouse lungs. RESULTS: Immunostaining demonstrated
      that the majority of the inflammatory cells recruited to FGF9-induced lung tumors
      were macrophages. These TAMs were enriched for the alternatively activated (M2)
      macrophage subtype. TAMs performed a significantly high immune suppressive
      function on T-cells and displayed high levels of arginase-1 expression and
      activity. The growth and colony forming potential of tumor cells was induced by
      co-culture with TAMs. Additionally, TAMs were shown to promote fibroblast
      proliferation and angiogenesis. TAMs had high expression of Tgf-beta, Vegf, Fgf2,
      Fgf10, Fgfr2 and several matrix metalloproteinases; factors that play multiple
      roles in supporting tumor growth, immune protection, fibroblast activation and
      angiogenesis. CONCLUSION: Our results provide evidence that the Fgf9-induced lung
      adenocarcinoma is associated with recruitment and activation of M2-biased TAMs,
      which provided multiple means of support to the tumor. This model represents an
      excellent means to further study the complex interactions between TAMs, their
      related chemokines, and progression of lung adenocarcinoma, and adds further
      evidence to support the importance of TAMs in tumorigenesis.

PMID- 29656750
TI  - Afatinib in heavily pretreated advanced NSCLC patients who progressed following
      prior gefitinib or erlotinib: Compassionate use program in Korea.
AB  - INTRODUCTION: Afatinib, an irreversible ErbB family blocker, approved for first
      line treatment of epidermal growth factor receptor (EGFR) mutated advanced non
      small cell lung cancer (NSCLC). This study investigated experience of afatinib
      within a compassionate use program (CUP). METHODS: The afatinib CUP was an open
      label, multicenter, single-arm program in Korea. We enrolled patients with stage
      IV NSCLC and who had received at least one line of previous cytotoxic
      chemotherapy and previous EGFR TKI treatment with either an EGFR mutation or
      documented clinical benefit. The starting dose of afatinib was 50 mg once daily.
      RESULTS: From August 2011 to September 2014, 332 patients received at least one
      dose of afatinib. Most patients were registered in the CUP for fourth- or fifth
      line treatment with afatinib. Adverse events (AEs) occurred in 98.1% of patients,
      including 29.8% with serious AEs. The most common AEs (all grades) were diarrhea
      (90.1%) and skin rash (62.0%). Dose reductions occurred in 60.5% of patients and
      discontinuations due to AEs were reported in 11.1% of patients. The response rate
      and median time to treatment failure (TTF) were 27.4% and 3.3 months (CI 95%, 2.8
      3.8 months), respectively, in this highly pretreated population. In subgroup
      analysis, ECOG PS 0 or 1 and immediate pretreatment with pemetrexed monotherapy
      or a platinum doublet were associated with a longer TTF for afatinib.
      CONCLUSIONS: No additional or unexpected safety concerns were observed, and
      afatinib demonstrated moderate antitumor activity in advanced NSCLC patients with
      acquired resistance to gefitinib or erlotinib in a real-world setting.

PMID- 29656751
TI  - Circulating tumor DNA testing in advanced non-small cell lung cancer.
AB  - Circulating tumor DNA (ctDNA) shed from cancer cells into the peripheral blood
      can be non-invasively collected and tested for the presence of tumor-specific
      mutations. Mutations identified in ctDNA can predict responses to targeted
      therapies and emerging evidence suggests that changes in ctDNA levels over time
      can be used to monitor response to therapy and detect disease recurrence. Given
      the emergence of targeted therapies in advanced non-small cell lung cancer
      (NSCLC), liquid biopsies utilizing ctDNA testing represent a powerful approach to
      genotype tumors and monitor for the development of resistance. Here, we review
      current and potential future clinical applications of ctDNA testing for patients
      with advanced NSCLC.

PMID- 29656752
TI  - Large cell neuroendocrine lung carcinoma induces peripheral T-cell repertoire
      alterations with predictive and prognostic significance.
AB  - OBJECTIVES: This study was performed to evaluate for a potentially important role
      of T cells in the pathophysiology and treatment sensitivity of large cell
      neuroendocrine lung carcinoma (LCNEC), an orphan disease with poor prognosis and
      scarce data to guide novel therapeutic strategies. MATERIALS AND METHODS: We
      performed T-cell receptor (TCR) beta-chain spectratyping on blood samples of
      patients treated within the CRAD001KDE37 trial (n = 35) using age-matched current
      or former (n = 11) and never smokers (n = 10) as controls. The data were analyzed
      in conjunction with the complete blood counts of the probands as well as the data
      about response to treatment and overall survival in the clinical trial. RESULTS
      AND CONCLUSION: Untreated stage IV LCNEC patients had significant T-cell
      repertoire alterations (p < 0.001) compared to age-matched smokers. These changes
      correlated positively with blood lymphocyte counts (r = 0.49, p < 0.01),
      suggesting antigen-induced T-cell proliferation as the causative mechanism. At
      the same time, LCNEC patients showed mild lymphopenia (1.54 vs. 2.51/nl in
      median, p < 0.01), which reveals a second, antigen-independent mechanism of
      systemic immune dysregulation. More pronounced T-cell repertoire alterations and
      higher blood lymphocyte counts at diagnosis were associated with a better
      treatment response by RECIST and with a longer overall survival (441 vs. 157 days
      in median, p = 0.019). A higher degree of T-cell repertoire normalization after 3
      months of therapy also distinguished a patient group with more favourable
      prognosis (median overall survival 617 vs. 316 days, p = 0.036) independent of
      radiological response. Thus, LCNEC induces clinically relevant changes of the T
      cell repertoire, which are measurable in the blood and could be exploited for
      prognostic, predictive and therapeutic purposes. Their pathogenesis appears to
      involve antigen-induced oligoclonal T-cell expansions superimposed on TCR
      independent lymphopenia.

PMID- 29656753
TI  - Extraction of radiomic values from lung adenocarcinoma with near-pure subtypes in
      the International Association for the Study of Lung Cancer/the American Thoracic
      Society/the European Respiratory Society (IASLC/ATS/ERS) classification.
AB  - INTRODUCTION: Histological subtypes of lung adenocarcinomas (ADCs) classified by
      the International Association for the Study of Lung Cancer/American Thoracic
      Society/European Respiratory Society (IASLC/ATS/ERS) system have been
      investigated using radiomic approaches. However, the results have had limitations
      since <80% of invasive lung ADCs were heterogeneous, with two or more subtypes.
      To reduce the influence of heterogeneity during radiomic analysis, computed
      tomography (CT) images of lung ADCs with near-pure ADC subtypes were analyzed to
      extract representative radiomic features of different subtypes. METHODS: We
      enrolled 95 patients who underwent complete resection for lung ADC and a
      pathological diagnosis of a "near-pure" (>=70%) IASLC/ATS/ERS histological
      subtype. Conventional histogram/morphological features and complex radiomic
      features (grey-level-based statistical features and component variance-based
      features) of thin-cut CT data of tumor regions were analyzed. A prediction model
      based on leave-one-out cross-validation (LOOCV) and logistic regression (LR) was
      used to classify all five subtypes and three pathologic grades (lepidic,
      acinar/papillary, micropapillary/solid) of ADCs. The validation was performed
      using 36 near-pure ADCs in a later cohort. RESULTS: A total of 31 lepidic, 14
      papillary, 32 acinar, 10 micropapillary, and 8 solid ADCs were analyzed. With 21
      conventional and complex radiomic features, for 5 subtypes and 3 pathological
      grades, the prediction models achieved accuracy rates of 84.2% (80/95) and 91.6%
      (87/95), respectively, while accuracy was 71.6% and 85.3%, respectively, if only
      conventional features were used. The accuracy rate for the validation set (n =
      36) was 83.3% (30/36) and 94.4% (34/36) in 5 subtypes and 3 pathological grades,
      respectively, using conventional and complex features, while it was 66.7% and
      77.8% only using conventional features, respectively. CONCLUSION: Lung ADC with
      high purity pathological subtypes demonstrates strong stratification of radiomic
      values, which provide basic information for accurate pathological subtyping and
      image parcellation of tumor sub-regions.

PMID- 29656754
TI  - Malignant cells from pleural fluids in malignant mesothelioma patients reveal
      novel mutations.
AB  - OBJECTIVES: Malignant mesothelioma (MM) is an asbestos related tumour affecting
      cells of serosal cavities. More than 70% of MM patients develop pleural effusions
      which contain tumour cells, representing a readily accessible source of malignant
      cells for genetic analysis. Although common somatic mutations and losses have
      been identified in solid MM tumours, the characterization of tumour cells within
      pleural effusions could provide novel insights but is little studied. MATERIALS
      AND METHODS: DNA and RNA were extracted from cells from short term cultures of 27
      human MM pleural effusion samples. Whole exome and transcriptome sequencing was
      performed using the Ion Torrent platform. Somatic mutations were identified using
      VarScan2 and SomaticSniper. Copy number alterations were identified using
      ExomeCNV in R. Significant copy number alterations were identified across all
      samples using GISTIC2.0. The association between tumour intrinsic properties and
      survival was analyzed using the Cox proportional hazards regression model.
      RESULTS: We identified BAP1, CDKN2A and NF2 alterations in the cells from MM
      pleural effusions at a higher frequency than what is typically seen in MM tumours
      from surgical series. The median mutation rate was 1.09 mutations/Mb. TRAF7 and
      LATS2 alterations were also identified at a high frequency (66% and 59%
      respectively). Novel regions of interest were identified, including alterations
      in FGFR3, and the regions 19p13.3, 8p23.1 and 1p36.32. CONCLUSION: Short term
      cultures of tumour cells from MM pleural effusions offer an accessible
      alternative to surgical tumour biopsies in the study of MM genomics and reveal
      novel mutations of interest. Pleural effusion tumour cells provide an opportunity
      for the monitoring of tumour dynamics, treatment response and the clonal
      evolution of MM tumours.

PMID- 29656755
TI  - The burden of lung cancer in Latin-America and challenges in the access to
      genomic profiling, immunotherapy and targeted treatments.
AB  - Lung cancer is a public health problem worldwide and Latin America (LATAM) cannot
      escape this reality. This malignant disease has not only a high prevalence in the
      region, but is also the main cause of cancer related deaths, and in other
      emerging countries, the incidence rates are still on the rise. Interestingly in
      most LATAM countries, lung cancer mortality has been decreasing in men but not in
      women, reflecting smoking patterns in countries such as Chile, Bolivia, and
      Brazil. Despite the fact that these issues are well known to government agencies,
      physicians and patients in the region, current efforts still fall behind those
      needed in order to face this problem of epidemic proportions. Tobacco control and
      smoking cessation are the most important interventions against lung cancer, but
      even with their optimal implementation (which is far from reality at this time)
      the number of cases in the foreseeable future would still be significant. Beyond
      tobacco control, advances in our understanding of the molecular component of lung
      cancer have resulted in new targeted therapies and immune check point inhibitors,
      which have improved clinical outcomes but at a considerably higher financial
      cost. LATAM has not widely and speedily adopted these strategies, including new
      technology and approved novel drugs, due to a number of facts, and therefore only
      a dismal proportion of LATAMs patient population have benefited from these new
      advances. A keen focus on a heterogeneous education system for caregivers in lung
      cancer treatment would likely help standardize care and improve future potential
      gains from domestic research. In this review we discuss the challenges of
      treatment implementation, focusing on new technologies.

PMID- 29656756
TI  - Correlation of tumor-related immunity with 18F-FDG-PET in pulmonary squamous-cell
      carcinoma.
AB  - OBJECTIVES: 2-Deoxy-2-[fluorine-18] fluoro-d-glucose with positron emission
      tomography (18F-FDG-PET) is a clinically useful tool for cancer evaluation. 18F
      FDG accumulation in tumor cells is known to be correlated with the presence of
      glucose transporter 1 (GLUT1) and hypoxia-inducible factor-1alpha (HIF-1alpha).
      Although anti-programmed death-1 (PD-1) antibody treatments have been approved,
      no suitable predictor of significant responders has been identified. Based on the
      existing information, we investigated the relationship between tumor immunity
      (including PD-L1) and 18F-FDG uptake in patients with surgically resected
      pulmonary squamous-cell carcinoma (SQC). MATERIALS AND METHODS: This study
      included 167 patients (153 men and 14 women) with SQC who underwent 18F-FDG PET.
      Tumor sections were stained by immunohistochemistry for GLUT1, HIF-1alpha, PD-L1,
      CD4, CD8, and Foxp3. The relationship between clinicopathological features and
      18F-FDG uptake was analyzed. Student's t-test, the chi2 test, non-parametric
      Spearman's rank test and the Kaplan-Meier method were used to show associations
      between variables. RESULTS: The rate of positive PD-L1 expression was 79%
      (132/167), and PD-L1 expression was significantly associated with GLUT1 (P <
      0.01), HIF-1alpha (P < 10-4), and CD8 (P < 1 * 10-3) expression. The SUVmax of
      18F-FDG was significantly correlated with PD-L1 (P = 0.02) and GLUT1 (P < 0.01)
      expression. Multivariate analysis demonstrated that advanced stage, elevated PD
      L1 expression, and elevated SUVmax were independent prognostic factors for
      predicting poor OS. Among patients with a high SUVmax, multivariate analysis
      confirmed that advanced stage and high PD-L1 expression were independent
      prognostic factors for poor OS; however, there was no significant difference
      among patients with a low SUVmax. CONCLUSION: High SUVmax on 18F-FDG-PET is
      associated with PD-L1 expression but is an independent prognostic factor for OS
      in our population of surgically resected pulmonary squamous-cell carcinoma.

PMID- 29656757
TI  - Associations of objectively assessed physical activity and sedentary time with
      health-related quality of life among lung cancer survivors: A quantile regression
      approach.
AB  - OBJECTIVES: No studies have examined objectively assessed physical activity,
      sedentary time, and patient-reported outcomes among lung cancer survivors. The
      objective of this study was to determine associations of objectively assessed
      moderate-to-vigorous intensity physical activity (MVPA) and sedentary time with
      health-related quality of life (HRQoL) and fatigue among lung cancer survivors.
      MATERIALS AND METHOD: Lung cancer survivors in Southern Alberta (N = 540) were
      invited to complete a mailed survey that assessed HRQoL [Functional Assessment of
      Cancer Therapy-Lung (FACT-L)], physical and functional well-being [Trial Outcome
      Index (TOI)], and fatigue [Fatigue Scale (FS)]. Physical activity and sedentary
      time data was collected using an Actigraph(r) GT3X+ accelerometer that was worn
      on the hip for seven consecutive days. Quantile regression was used to examine
      associations of HRQoL and fatigue with physical activity and sedentary time at
      the 25th, 50th, and 75th HRQoL and fatigue percentiles. RESULTS: A total of 127
      lung cancer survivors participated for a 24% response rate (Mean age = 71 years;
      Mean time since diagnosis = 75 months). Total MVPA minutes was positively
      associated with fewer fatigue symptoms at the 25th percentile (beta = 0.16, p =
      0.046). Total sedentary time was inversely associated with HRQoL at the 75th
      percentile (beta = -0.07, p = 0.014) and inversely associated with fatigue
      symptoms at the 50th percentile (beta = -0.04, p = 0.009). Total sedentary time
      was also inversely associated with physical and functional well-being scores at
      the 25th (beta = -0.07, p = 0.045), 50th (beta = -0.07, p = 0.004) and 75th (beta
      = -0.04, p = 0.035) percentiles. CONCLUSION: Across the HRQoL, fatigue, and
      physical and functional well-being distributions, sedentary time was inversely
      associated with HRQoL, fatigue, and physical and functional well-being in lung
      cancer survivors. Small associations were observed between MVPA and fatigue, but
      no associations emerged with HRQoL or physical and functional well-being.

PMID- 29656759
TI  - Physical behavior and associations with health outcomes in operable NSCLC
      patients: A prospective study.
AB  - OBJECTIVES: Our objectives were to 1) characterize daily physical behavior of
      operable non-small cell lung cancer (NSCLC) patients, from preoperative to six
      months postoperative using accelerometry, and explore if physical behavior
      preoperative or one month postoperative is associated with better health outcomes
      at six months postoperative. METHODS: A prospective study with 23 patients (13
      female) diagnosed with primary NSCLC and scheduled for curative lung resection
      was performed. Outcome measures were assessed two weeks preoperative, and one,
      three and six months postoperative, and included accelerometer-derived physical
      behavior measures and the following health outcomes: six minute walking distance
      (6MWD), questionnaires concerning health-related quality of life (HRQOL), fatigue
      and distress. RESULTS: On group average, physical behavior showed significant
      changes over time. Physical behavior worsened following surgery, but improved
      between one and six months postoperative, almost reaching preoperative levels.
      However, physical behavior showed high variability between patients in both
      amount as well as change over time. More time in moderate-to-vigorous physical
      activity in bouts of 10 min or longer in the first month postoperative was
      significantly associated with better 6MWD, HRQOL, distress, and fatigue at six
      months postoperative. CONCLUSION: As expected, curative lung resection impacts
      physical behavior. Patients who were more active in the first month following
      surgery reported better health outcome six months postoperative. The large
      variability in activity patterns over time observed between patients, suggests
      that physical behavior 'profiling' through detailed monitoring of physical
      behavior could facilitate tailored goal setting in interventions that target
      change in physical behavior.

PMID- 29656758
TI  - Feasibility of endobronchial ultrasound transbronchial needle aspiration for
      massively parallel next-generation sequencing in thoracic cancer patients.
AB  - INTRODUCTION: Next-generation sequencing (NGS) allows for the identification of a
      growing number of therapeutic and prognostic molecular targets. However, NGS
      typically requires greater quantities of DNA than traditional molecular testing
      does. Endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) is a
      minimally invasive procedure used to sample central thoracic lesions, but it is
      not well established whether this technique provides sufficient material for NGS.
      METHODS: We performed a retrospective review of EBUS-TBNA at our institution
      (3/1/14-9/28/16). NGS was performed using a comprehensive hybrid-capture based
      assay (MSK-IMPACT) that detects >340 gene mutations. Samples found to be
      diagnostic for malignancy and for which MSK-IMPACT had been attempted were
      identified. Pathologic and clinical data were obtained from the medical record,
      and the results of MSK-IMPACT were examined. RESULTS: In total, 784 EBUS-TBNA
      procedures were performed during the study period. MSK-IMPACT was requested for
      115 malignant samples and was successful for 99 (86.1%), identifying an average
      of 12.7 mutations at a mean coverage depth of 806X. NGS was performed on paraffin
      embedded cell blocks in 93 cases (93.9%) and on cell-free DNA in needle rinse
      fluid in 6 cases. The success rate of the assay improved significantly from the
      first third of cases (76.3%), to 92.3% for the final one-third of cases (p <
      0.05). CONCLUSIONS: EBUS-TBNA reliably provided adequate tissue for hybrid
      capture NGS, and is a suitable option for comprehensive NGS testing in patients
      with thoracic malignancies.

PMID- 29656760
TI  - Successful treatment with brigatinib in a patient with ALK-rearranged lung
      adenocarcinoma who developed crizotinib-induced interstitial lung disease.
AB  - We present a 45-year-old patient diagnosed with anaplastic lymphoma kinase (ALK)
      rearranged metastatic lung cancer who developed grade 4 interstitial lung disease
      (ILD) while on crizotinib treatment and was lately treated with brigatinib with
      no reappearance of ILD. To our knowledge, this is the first case report of
      successful treatment with brigatinib after crizotinib-induced ILD. Even though
      ILD secondary to brigatinib has been reported in clinical trials, no pulmonary
      toxicity has been seen in our patient, suggesting no crosslink lung toxicity
      between crizotinib and brigatinib.

PMID- 29656761
TI  - Adsorption of organic molecules on mineral surfaces studied by first-principle
      calculations: A review.
AB  - First-principle calculations, especially by the density functional theory (DFT)
      methods, are becoming a power technique to study molecular structure and
      properties of organic/inorganic interfaces. This review introduces some recent
      examples on the study of adsorption models of organic molecules or oligomers on
      mineral surfaces and interfacial properties obtained from first-principles
      calculations. The aim of this contribution is to inspire scientists to benefit
      from first-principle calculations and to apply the similar strategies when
      studying and tailoring interfacial properties at the atomistic scale, especially
      for those interested in the design and development of new molecules and new
      products.

PMID- 29656762
TI  - Clinical guideline on bone conduction implants.
AB  - INTRODUCTION AND GOALS: During the last decade there have been multiple and
      relevant advances in conduction and mixed hearing loss treatment. These advances
      and the appearance of new devices have extended the indications for bone
      conduction implants. The Scientific Committee of Audiology of the Sociedad
      Espanola de Otorrinolaringologia y Cirugia de Cabeza y Cuello SEORL-CCC (Spanish
      Society of Otolaryngology and Head and Neck Surgery), together with the Otology
      and Otoneurology Committees, have undertaken a review of the current state of
      bone-conduction devices with updated information, to provide a clinical guideline
      on bone-conduction implants for otorhinolaryngology specialists, health
      professionals, health authorities and society in general. METHODS: This clinical
      guideline on bone-conduction implants contains information on the following: 1)
      Definition and description of bone-conduction devices; 2) Current and upcoming
      indications for bone conduction devices: Magnetic resonance compatibility; 3)
      Organization requirements for a bone-conduction implant programme. RESULTS AND
      CONCLUSIONS: The purpose of this guideline is to describe the different bone
      conduction implants, their characteristics and their indications, and to provide
      coordinated instructions for all the above-mentioned agents for decision making
      within their specific work areas.

PMID- 29656763
TI  - WITHDRAWN: Combination of NSAID and Antitussives in Treatment of URTI Related
      Cough: An Observational Study.
AB  - The Publisher regrets that this article is an accidental duplication of an
      article that has already been published in Eur Respir J. 46 (2015) PA3852,
      http://dx.doi.org/10.1183/13993003.congress-2015.PA3852. The duplicate article
      has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can
      be found at https://www.elsevier.com/about/our-business/policies/article
      withdrawal.

PMID- 29656765
TI  - Telltale Hairs.

PMID- 29656764
TI  - Prescribing Habits for Androgenic Alopecia Among Dermatologists in Spain in 2017:
      A Cross-Sectional Study.
AB  - BACKGROUND: Topical minoxidil and oral finasteride are the only drugs approved
      for the treatment of androgenetic alopecia (AGA) in Spain. However, the
      management of this condition is highly variable because numerous treatments are
      used off-label. The main aim of this study was to describe the prescribing habits
      of dermatologists in Spain for male AGA (MAGA) and female AGA (FAGA). MATERIAL
      AND METHODS: Descriptive cross-sectional study using online questionnaires
      completed by dermatologists working in Spain. RESULTS: The responses of 241
      dermatologists were analyzed. The most common treatments prescribed for MAGA were
      minoxidil (98%), oral finasteride (96%), nutricosmetics (44%), topical
      finasteride (37%), oral dutasteride (33%), platelet-rich plasma (14%), and low
      level laser therapy (8%). For premenopausal FAGA, the most common treatments were
      topical minoxidil (98%), oral contraceptives (81%), nutricosmetics (72%),
      cyproterone acetate (58%), oral finasteride (39%), topical finasteride (39%),
      spironolactone (27%), platelet-rich plasma (20%), oral dutasteride (20%), oral
      flutamide (18%), and low-level laser therapy (7%). Finally, for postmenopausal
      FAGA, the most common treatments prescribed were topical minoxidil (98%), oral
      finasteride (84%), nutricosmetics (68%), topical finasteride (50%), oral
      dutasteride (35%), platelet-rich plasma (21%), spironolactone (16%), cyproterone
      acetate (16%), oral flutamide (9%), and low-level laser therapy (9%). A
      limitation of our study is that we did not analyze novel AGA treatments such as
      oral minoxidil and dutasteride mesotherapy. CONCLUSIONS: The most common
      treatments prescribed for AGA by dermatologists in Spain are topical minoxidil,
      oral finasteride, and nutricosmetics for MAGA and postmenopausal FAGA and topical
      minoxidil, oral contraceptives, and nutricosmetics for premenopausal FAGA.

PMID- 29656766
TI  - Hereditary paraganglioma-pheochromocytoma syndrome.

PMID- 29656767
TI  - Restrictions of nitrofurantoin: Lights and shadows.

PMID- 29656769
TI  - Population Control in Small Animals.
AB  - Optimal age for ovariohysterectomy or castration has not been defined in the
      scientific literature. Bitches and queens are significantly less likely to
      develop mammary neoplasia, which has a high incidence and potentially high
      morbidity and mortality, if spayed when young. Tom cats exhibit undesirable
      behaviors that preclude them being good pets and should be castrated young. There
      is no compelling reason to castrate male dogs when young unless it is needed to
      control reproductive behaviors or prevent indiscriminate breeding. Alternatives
      to surgical sterilization that may be available in the future include
      intratesticular injection and immunization against gonadotropin-releasing
      hormone.

PMID- 29656770
TI  - Assisted Reproduction in the Female Cat.
AB  - Assisted reproduction in the queen can range from simple ovulation induction to
      more advanced techniques such as in vitro fertilization. This article describes
      techniques available and the success associated with each.

PMID- 29656768
TI  - A rare variant in MLKL confers susceptibility to ApoE E4-negative Alzheimer's
      disease in Hong Kong Chinese population.
AB  - Alzheimer's disease (AD) is the most common neurodegenerative disorders in the
      elderly. To identify rare genetic factors other than apolipoprotein E E4 allele
      (ApoE E4) contributing to the pathogenesis of late-onset AD (LOAD), we conducted
      a whole-exome analysis of 246 ApoE E4-negative LOAD cases and 172 matched
      controls in Hong Kong Chinese population. LOAD patients showed a significantly
      higher burden of rare loss-of-function variants in genes related to immune
      function than healthy controls. Among the genes involved in immune function, we
      identified a rare stop-gain variant (p.Q48X) in mixed lineage kinase domain like
      pseudokinase (MLKL) gene present exclusively in 6 LOAD cases. MLKL is expressed
      in neurons, and the its expression levels in the p.Q48X carriers were
      significantly lower than that in age-matched wild-type controls. The ratio of
      Abeta42 to Abeta40 significantly increased in MLKL knockdown cells compared to
      scramble controls. MLKL loss-of-function mutation might contribute to late-onset
      ApoE E4-negative AD in the Hong Kong Chinese population.

PMID- 29656771
TI  - Been There, Done That: A Practical Primer for Veterinarians Considering Inclusion
      of Small Animal Theriogenology Services in Their Practice.
AB  - Broadening your scope of practice to include theriogenology services offers a
      myriad of advantages. Theriogenology services are profitable, offer new revenue
      streams, and optimize the use of support staff and hospital. Offering
      reproductive services sets your practice apart from competitor practices. Breeder
      clients are demanding but loyal and return for repeat services; they also request
      and follow recommendations for "high-end" services. Your theriogenology clients
      often refer locally placed puppies and kittens to you for primary care and you
      gain new general practice clients. And it is fun!

PMID- 29656772
TI  - Mismating Diagnosis and Protocols.
AB  - Mismating, or termination of pregnancy, is a commonly requested reproductive
      procedure for bitches and queens. Surgical treatment via ovariohysterectomy is
      the preferred choice when bitches or queens are not desired for future breeding
      purposes. Animals that are reproductively valuable can be treated with a variety
      of drugs to terminate the pregnancy. The choice of specific medical therapy is
      based on safety, efficacy, availability of the drug, and gestational age of the
      pregnancy. Currently, there is no US Food and Drug Administration-approved
      treatment of mismating in North America for dogs or cats.

PMID- 29656774
TI  - Connecting the dots in mental illness: The synapse as the intersection of brain
      function and disease.

PMID- 29656773
TI  - Assisted Reproduction in the Male Cat.
AB  - The demand for feline semen collection, evaluation, and subsequent use is growing
      as a way to preserve important genetic materials. This article describes semen
      collection methods using a variety of techniques that can be applicable in almost
      any setting. Also discussed are cryopreservation methods that optimize sperm
      survival.

PMID- 29656775
TI  - The NCI Physical Sciences - Oncology Network.
AB  - Nastaran Zahir is Associate Director of the Physical Sciences - Oncology Network
      in the Division of Cancer Biology at the National Cancer Institute. Dr. Zahir
      coordinates cross-cutting efforts to integrate physical sciences perspectives
      with cancer research by fostering transdisciplinary research collaborations,
      supporting education and outreach programs, and promoting resources for data
      sharing and biospecimen standards.

PMID- 29656776
TI  - Purulenta pericarditis and Pasteurella multocida: an extremely rare entity.
AB  - Purulent pericarditis is a rare entity, defined as the presence of neutrophilic
      pericardial effusion which is infected by a bacterial, fungus or parasite agent.
      The diagnosis can be challenging, especially if patients have taken previous
      antibiotic therapy; on the other hand the recognition of this pathology is often
      made late, with the onset of severe symptoms or signs of cardiac tamponade or
      even only at the autopsy. The authors describe the case of a 82-year-old woman
      with history of extensive laceration of the right lower limb from a dog bite in
      July 2016, admitted to the Cardiology Department one month later for Acute
      Pericarditis. During hospitalization she maintained recurrent fever peaks despite
      the treatment with non-steroidal anti-inflammatory drugs and colchicine. She
      collected blood cultures and repeated echocardiogram showed increased pericardial
      effusion with no signs of hemodynamic compromise. Blood cultures revealed the
      presence of Pasteurella multocida. Due to clinical suspicion of purulent
      pericarditis, pericardiocentesis was performed with drainage of liquid compatible
      with exudate and the patient was presented to the Cardiothoracic Surgery
      Department for pericardiotomy and adequate drainage of the liquid. Histological
      examination confirmed the diagnosis of Acute Pericarditis. It should be noted
      that Pasteurella is a very frequent agent (50-90%) in the gastrointestinal tract
      and nasopharynx of many domestic animals, namely dogs. The authors emphasize the
      need to aggressively treat this pathology, since untreated death is inevitable.

PMID- 29656779
TI  - Erratum to "microRNAs as mediators of insect host-pathogen interactions and
      immunity" [Journal of Insect Physiology 70 (2014) 151-158].

PMID- 29656780
TI  - Abnormal P-Wave Axis and Risk of Atrial Fibrillation: Not Just the Left Atrial
      Enlargement but Other Factors Also Play a Significant Role.

PMID- 29656781
TI  - Observational and Genetic Associations of Resting Heart Rate With Aortic Valve
      Calcium.
AB  - It is unknown if lifelong exposure to increased hemodynamic stress from an
      elevated resting heart rate (HR) may contribute to aortic valve calcium (AVC). We
      performed multivariate regression analyses using data from 1,266 Framingham Heart
      Study (FHS) Offspring cohort participants and 6,764 Multi-Ethnic Study of
      Atherosclerosis (MESA) participants. We constructed a genetic risk score (GRS)
      for HR using summary-level data in the Cohorts for Heart and Aging Research in
      Genomic Epidemiology (CHARGE) AVC Consortium to investigate if there was evidence
      in favor of a causal relation. AVC was present in 39% of FHS Offspring cohort
      participants and in 13% of MESA cohort participants. In multivariate adjusted
      models, participants in the highest resting HR quartiles had significantly
      greater prevalence of AVC, with a prevalence ratio of 1.19 (95% confidence
      interval [CI] 0.99 to 1.44) for the FHS Offspring cohort and 1.32 (95% CI 1.12 to
      1.63) for the MESA cohort, compared with those in the lowest quartile. There was
      a similar increase in the prevalence of AVC per standard deviation increase in
      resting HR in both FHS Offspring (prevalence ratio 1.08, 95% CI 1.01 to 1.15) and
      MESA (1.10, 95% CI 1.03 to 1.17). In contrast with these observational findings,
      a HR associated GRS was not significantly associated with AVC. Although our
      observational analysis indicates that a higher resting HR is associated with AVC,
      our genetic results do not support a causal relation. Unmeasured environmental
      and/or lifestyle factors associated with both increased resting HR and AVC that
      are not fully explained by covariates in our observational models may account for
      the association between resting HR and AVC.

PMID- 29656782
TI  - Response to: evaluation of sarcopenia in children.

PMID- 29656783
TI  - Nationwide overview of survival and management of appendiceal tumors in children.
AB  - INTRODUCTION: There remains a paucity of literature on survival related to
      pediatric appendiceal tumors. The purpose of this study was to determine the
      incidence, surgical management, and survival outcomes of appendiceal tumors in
      pediatric patients. METHODS: The Surveillance, Epidemiology, and End Results
      (SEER) Registry was analyzed for pediatric appendiceal tumors from 1973 to 2011.
      Parameters analyzed were: tumor type, surgical management (appendectomy vs.
      extensive resection), tumor size, and lymph node sampling. Chi-square analysis
      for categorical and Student's t test for continuous data were used. RESULTS:
      Overall, 209 patients had an appendiceal tumor, including carcinoid (72%),
      appendiceal adenocarcinoma (16%), and lymphoma (12%). Patients undergoing
      appendectomy vs. extensive resection had similar 15-year survival rates (98% vs.
      97%; p=0.875). Appendectomy vs. extensive resection conferred no 15-year survival
      advantage when patients were stratified by tumor type, including adenocarcinoma
      (87% vs. 89%; p=0.791), carcinoid (100% vs. 100%; p=0.863), and lymphoma (94% vs.
      100%; p=0.639). There was no significant difference in 15-year survival between
      tumor size groups >=2 and <2cm (both 100%) and presence or absence of lymph node
      sampling (96% and 97%; p=0.833) for all patients with a carcinoid tumor.
      CONCLUSION: Appendectomy may be adequate for pediatric appendiceal tumors.
      Extensive resection may be of limited utility for optimizing patient survival,
      placing patient at greater operative risk. TYPE OF STUDY: Retrospective
      Prognostic Study. LEVEL OF EVIDENCE: III.

PMID- 29656784
TI  - Combined Contribution of Reduced Functional Mobility, Muscle Weakness, and Low
      Serum Albumin in Prediction of All-Cause Mortality in Hemodialysis Patients: A
      Retrospective Cohort Study.
AB  - OBJECTIVES: The combined effects of reduced functional mobility, muscle weakness,
      and low serum albumin on mortality in hemodialysis patients have not been
      clarified. Here, we examined the associations of reduced functional mobility,
      muscle weakness, and low serum albumin-both alone and in combination-with all
      cause mortality in hemodialysis patients. METHODS: A total of 490 patients
      treated between July 2010 and October 2016 were enrolled retrospectively in this
      study. The independent prognostic effect of the combination of reduced functional
      mobility, muscle weakness, and low serum albumin on survival was estimated by Cox
      proportional hazard regression analysis. We calculated the increases in
      predictive capacity by combining the associations of reduced functional mobility,
      muscle weakness, and low serum albumin in comparison to each component alone
      based on the receiver-operating characteristic curves, continuous net
      reclassification improvement (NRI), and integrated discrimination improvement
      (IDI). RESULTS: The final study population consisted of 314 hemodialysis
      patients, and 56 patients died during the 6.5-year follow-up period. The high
      Combined score group showed a significantly lower cumulative survival rate than
      the low Combined score group (hazard ratio, 3.30; 95% confidence interval, 1.59
      6.87; P = .001). Both NRI and IDI suggested that the addition of Combined score
      to patient characteristics improved discrimination of patients at high risk of
      mortality (NRI, 0.038 95% CI: 0.096 - 0.064, P < .001 IDI, 0.029 95% CI: 0.004 -
      0.055, P = .025). CONCLUSIONS: The combined assessment of reduced functional
      mobility, muscle weakness, and low serum albumin was associated with poorer
      prognosis in patients on hemodialysis. The results presented here indicated that
      the combination of reduced functional mobility, muscle weakness, and low serum
      albumin is useful for accurate prediction of prognosis in hemodialysis patients.

PMID- 29656785
TI  - Cancer Immunotherapy 2017 (Paris, France). Progress and challenges.

PMID- 29656786
TI  - Numerical investigation of band spreading generated by flow-through needle and
      fixed loop sample injectors.
AB  - The present study reports on a computational fluid dynamics study of the band
      broadening occurring in injector systems frequently used in contemporary liquid
      chromatography instruments. The aim of this work is to determine band broadening
      originating purely from the injection volume in absence of any other possible
      contribution (e.g. band broadening due to the injection valve) and to unravel the
      mechanism behind it. Simulations of the dispersion process in flow through needle
      injectors were performed. In addition, fixed loop injectors were also simulated
      and comparison with flow through needle injectors was made. The results are also
      represented in a dimensionless form, allowing to generalize them to different
      experimental conditions. It was shown that two different injection regimes exist
      (the convection regime and the diffusion regime), both leading to narrow
      injection bands, while operating the injection needle in between the two regimes
      leads to broad injections bands. It was also found that the band broadening in
      the flow-through needle injector is strongly affected by the holding time between
      sample uptake and the actual injection. As a result, fixed, full loop injectors
      produced narrower injection bands compared to flow-through needle injectors
      operated with a realistic holding time.

PMID- 29656787
TI  - Fifty-Year Incidence of Waldenstrom Macroglobulinemia in Olmsted County,
      Minnesota, From 1961 Through 2010: A Population-Based Study With Complete Case
      Capture and Hematopathologic Review.
AB  - OBJECTIVE: To determine the incidence of Waldenstrom macroglobulinemia (WM) in a
      strictly defined geographic area over a 50-year period. PATIENTS AND METHODS: All
      residents of Olmsted County with a diagnosis of WM, consisting of a monoclonal
      IgM protein of any size and/or 10% or more lymphoplasmacytic infiltration of the
      bone marrow along with anemia, constitutional symptoms, hyperviscosity,
      lymphadenopathy, or hepatosplenomegaly requiring therapy, were identified from
      January 1, 1961, to December 31, 2010. Patients with smoldering WM,
      lymphoplasmacytic lymphoma with an IgG or IgA monoclonal protein, and those with
      an IgM monoclonal gammopathy of undetermined significance were excluded. The
      peripheral blood smears, bone marrow aspirates, and biopsy specimens were
      reviewed by an experienced hematopathologist. RESULTS: Twenty-two patients were
      identified as having WM. The age-adjusted incidence rate for males was 0.92 per
      100,000 person-years (95% CI, 0.44-1.39 per 100,000 person-years) and for females
      was 0.30 per 100,000 person-years (95% CI, 0.08-0.53 per 100,000 person-years)
      with an age- and sex-adjusted incidence of 0.57 per 100,000 person-years (95% CI,
      0.33-0.81 per 100,000 person-years). When evaluated using a smoothing spline,
      there was no convincing evidence for a change in the incidence of WM over the
      past 50 years. Patients diagnosed with WM after 2000 had an approximately 2-fold
      excess mortality compared with the expected population mortality (standardized
      mortality ratio, 2.4; 95% CI, 0.64-6.0). CONCLUSION: Waldenstrom
      macroglobulinemia is a rare malignancy, and the incidence in Olmsted County,
      Minnesota, has shown virtually no change over the past 50 years.

PMID- 29656788
TI  - Overweight Without Central Obesity, Cardiovascular Risk, and All-Cause Mortality.
AB  - OBJECTIVE: To assess the association of overweight without central obesity with
      risks of mortality. PATIENTS AND METHODS: We included 14,299 participants in the
      Third National Health and Nutrition Examination Survey (from October 18, 1988,
      through October 15, 1994). According to their body mass index and waist
      circumference, participants were categorized into 7 anthropometric groups.
      Logistic regression models were used to assess the relation of cardiovascular
      risk factors (hypertension, diabetes, or hypercholesterolemia) and 10-year
      cardiovascular risk to anthropometric groups. Cox proportional hazards models
      were used to assess the risk of all-cause mortality, and competing-risks
      regression models were used for calculating cardiovascular and noncardiovascular
      mortality. RESULTS: Compared with those with normal body mass index and waist
      circumference, overweight men without central obesity were more likely to have
      all 3 cardiovascular risk factors and a high cardiovascular risk, whereas women
      in this anthropometric group were more likely to have hypercholesterolemia. In
      proportional hazards models, overweight without central obesity was associated
      with lower all-cause mortality among men in the population with cardiovascular
      risk factors (hazard ratio, 0.71; 95% CI, 0.56-0.89; P=.004) and the general
      population (hazard ratio, 0.72; 95% CI, 0.60-0.87; P=.001), whereas results of
      these comparisons among women were not significant (P>.05). In competing risk
      analyses, overweight men without central obesity had a lower risk of
      noncardiovascular mortality, but not cardiovascular mortality. CONCLUSION:
      Although overweight without central obesity was associated with cardiovascular
      risk factors and a high cardiovascular risk among men, men in this anthropometric
      group had a lower mortality risk.

PMID- 29656789
TI  - Voice Signal Characteristics Are Independently Associated With Coronary Artery
      Disease.
AB  - OBJECTIVE: Voice signal analysis is an emerging noninvasive diagnostic tool. The
      current study tested the hypothesis that patient voice signal characteristics are
      associated with the presence of coronary artery disease (CAD). METHODS: The study
      population included 138 patients who were enrolled between January 1, 2015, and
      February 28, 2017: 37 control subjects and 101 subjects who underwent planned
      coronary angiogram. All subjects had their voice signal recorded to their
      smartphone 3 times: reading a text, describing a positive emotional experience,
      and describing a negative emotional experience. The Mel Frequency Cepstral
      Coefficients were used to extract prespecified voice features from all 3
      recordings. Voice was recorded before the angiogram and analysis was blinded with
      respect to patient data. RESULTS: Final study cohort included 101 patients, of
      whom 71 (71%) had CAD. Compared with subjects without CAD, patients with CAD were
      older (median, 63 years; interquartile range [IQR], 55-68 years vs median, 53
      years; IQR, 42-66 years; P=.003) and had a higher 10-year atherosclerotic
      cardiovascular disease (ASCVD) risk score (9.4%; IQR, 5.0-18.7 vs 2.7%; IQR, 1.6
      11.8; P=.005). Univariate binary logistic regression analysis identified 5 voice
      features that were associated with CAD (P<.05 for all). Multivariate binary
      logistic regression with adjustment for ASCVD risk score identified 2 voice
      features that were independently associated with CAD (odds ratio [OR], 0.37; 95%
      CI, 0.18-0.79; and 4.01; 95% CI, 1.25-12.84; P=.009 and P=.02, respectively).
      Both features were more strongly associated with CAD when patients were asked to
      describe an emotionally significant experience. CONCLUSION: This study suggests a
      potential relationship between voice characteristics and CAD, with clinical
      implications for telemedicine-when clinical health care is provided at a
      distance.

PMID- 29656790
TI  - Re: 'Killing two birds with one stone? Association between tobacco and alcohol
      consumption.'

PMID- 29656791
TI  - Cardiovascular risk factors predicting cardiac events are different in patients
      with rheumatoid arthritis, psoriatic arthritis, and psoriasis.
AB  - OBJECTIVES: Increased cardiovascular risk in rheumatoid arthritis (RA) is well
      established. Examining traditional cardiovascular risk factors alone
      underestimates cardiovascular risk in RA. Systematic inflammation, measured by
      erythrocyte sedimentation rate or C-reactive protein is also a major risk factor.
      However, the contribution of traditional cardiovascular risk factors (such as
      obesity and hyperlipidaemia) compared to inflammation is uncertain in psoriatic
      arthritis (PsA) and RA. We examine the incidence of major adverse cardiac events
      (MACE) among patients with RA, PsA psoriasis, and controls adjusting for risk
      factors, inflammation and disease modifying anti-rheumatic drug treatment, to
      better define cardiovascular risk. METHODS: Using the Secure Anonymised
      Information Linkage databank, comprising routinely collected Welsh health data
      from 1999 to 2013, the incidence and first occurrence of a MACE in individuals
      with RA (n = 8650), PsA (n = 2128) and psoriasis (n = 24,630) compared to
      controls (n = 11,87,706) was investigated. RESULTS: Traditional cardiovascular
      risk factors are higher in RA, PsA and psoriasis than controls. After adjusting
      for these factors, additional cardiovascular risk was only significantly
      increased in female RA patients (HR = 1.3; 95% CI: 1.0-1.7; p = 0.05) and
      psoriasis (HR = 1.2; 95% CI: 1.0-1.4; p = 0.02) but not statistically significant
      for PsA (HR = 1.5; 95% CI: 0.9-2.5; p = 0.13). ESR and CRP were increased in
      patients with RA but not in patients with psoriasis. CONCLUSION: Additional
      increased cardiovascular risk was observed in female RA and psoriasis but not
      PsA. Systematic inflammation is higher in RA but not psoriasis, indicating that
      there are varying mediators of cardiovascular risk across these conditions.

PMID- 29656792
TI  - Training children aged 5-10 years in manual compliance control to improve drawing
      and handwriting.
AB  - A large proportion of school-aged children exhibit poor drawing and handwriting.
      This prevalence limits the availability of therapy. We developed an automated
      method for training improved manual compliance control and relatedly, prospective
      control of a stylus. The approach included a difficult training task, while
      providing parametrically modifiable support that enables the children to perform
      successfully while developing good compliance control. The task was to use a
      stylus to push a bead along a 3D wire path. Support was provided by making the
      wire magnetically attractive to the stylus. Support was progressively reduced as
      3D tracing performance improved. We report studies that (1) compared performance
      of Typically Developing (TD) children and children with Developmental
      Coordination Disorder (DCD), (2) tested training with active versus passive
      movement, (3) tested progressively reduced versus constant or no support during
      training, (4) tested children of different ages, (5) tested the transfer of
      training to a drawing task, (6) tested the specificity of training in respect to
      the size, shape and dimensionality of figures, and (7) investigated the relevance
      of the training task to the Beery VMI, an inventory used to diagnose DCD. The
      findings were as follows. (1) Pre-training performance of TD and DCD children was
      the same and good with high support but distinct and poor with low support.
      Support yielded good self-efficacy that motivated training. Post training
      performance with no support was improved and the same for TD and DCD children.
      (2) Actively controlled movements were required for improved performance. (3)
      Progressively reduced support was required for good performance during and after
      training. (4) Age differences in performance during pre-training were eliminated
      post-training. (5) Improvements transferred to drawing. (6) There was no evidence
      of specificity of training in transfer. (7) Disparate Beery scores were reflected
      in pre-training but not post-training performance. We conclude that the method
      improves manual compliance control, and more generally, prospective control of
      movements used in drawing performance.

PMID- 29656793
TI  - Long noncoding RNA VIM-AS1 promotes colorectal cancer progression and metastasis
      by inducing EMT.
AB  - Emerging evidence indicates that lncRNAs play crucial roles in the initiation and
      progression of various malignant tumors. VIM-AS1 RNA is an lncRNA that
      transcribes from a shared bidirectional promoter with vimentin mRNA and its
      function in cancer cells is largely unknown. This study assessed the clinical
      significance of VIM-AS1 expression in colorectal cancer (CRC). We found that the
      VIM-AS1 transcript was significantly upregulated in high-grade, lymph node
      metastasis and vascular invasion tumors. Loss-of-function experiments revealed
      that the downregulation of VIM-AS1 could inhibit tumor cell proliferation by
      inducing apoptosis, cellular senescence and arresting the cell cycle. Moreover,
      the obtained data demonstrated that VIM-AS1 might play a crucial role in cell
      migration as well as the epithelial to mesenchymal transition (EMT) of CRC cells.
      Collectively, for the first time, our data provide novel evidence for the
      biological and clinical significance of VIM-AS1 expression in CRC. Further, the
      findings of this study suggest that VIM-AS1 promotes tumor growth and metastasis
      by inducing EMT in CRC cells and could be considered as a novel tumor marker with
      probable value in diagnosis and CRC treatment.

PMID- 29656794
TI  - Immunohistochemistry for mismatch repair protein deficiency in endometrioid
      endometrial carcinoma yields equivalent results when performed on endometrial
      biopsy/curettage or hysterectomy specimens.
AB  - OBJECTIVE: Universal screening of endometrial cancer (EC) for Lynch syndrome (LS)
      has been increasingly implemented in the past five to ten years. Most
      pathologists initiate screening with immunohistochemistry (IHC) for mismatch
      repair proteins (MMRPs), using either pre-surgical samplings (endometrial biopsy
      or curettage, EMB/C) or hysterectomy specimens. We report a systematic assessment
      of the equivalence of IHC for LS screening on EMB/C versus hysterectomy
      specimens. METHODS: We identified 99 patients diagnosed with endometrioid EC and
      performed IHC for MMRPs MLH1, MSH2, MSH6, and PMS2 on their diagnostic EMB/C and
      paired hysterectomy specimen. Each specimen was scored as MMRP-retained or MMRP
      deficient. RESULTS: Ninety-one EMB/Cs had carcinoma, while 8 EMB/Cs showed only
      complex atypical hyperplasia (CAH). Carcinoma was identified in all 99
      hysterectomy specimens. Considering all 99 patients tested, concordance of MMRP
      expression pattern between EMB/C and paired hysterectomy specimen was 100%. Sixty
      nine cases retained all four MMRPs, while 30 were MMRP deficient (26 MLH1- and
      PMS2-deficient, 3 MSH2- and MSH6-deficient, 1 PMS2-deficient). CONCLUSIONS: In
      screening for LS in EC, IHC for MMRPs can be performed with identical accuracy on
      either EMB/C or hysterectomy specimens. Routine testing of diagnostic EMB/Cs may
      lead to earlier detection of MMRP deficiency, with improved patient uptake of
      genetic counseling and potential for earlier identification of immunotherapy
      candidates. Furthermore, reliable IHC-based LS screening performed on EMB/C can
      guide patient management and genetic counseling in patients unable to undergo
      hysterectomy.

PMID- 29656795
TI  - Single-Cell Microgels: Technology, Challenges, and Applications.
AB  - Single-cell-laden microgels effectively act as the engineered counterpart of the
      smallest living building block of life: a cell within its pericellular matrix.
      Recent breakthroughs have enabled the encapsulation of single cells in sub-100
      MUm microgels to provide physiologically relevant microniches with minimal mass
      transport limitations and favorable pharmacokinetic properties. Single-cell-laden
      microgels offer additional unprecedented advantages, including facile
      manipulation, culture, and analysis of individual cell within 3D
      microenvironments. Therefore, single-cell microgel technology is expected to be
      instrumental in many life science applications, including pharmacological
      screenings, regenerative medicine, and fundamental biological research. In this
      review, we discuss the latest trends, technical challenges, and breakthroughs,
      and present our vision of the future of single-cell microgel technology and its
      applications.

PMID- 29656796
TI  - [Effect of influenza vaccination in Primary Healthcare workers and the general
      population in Gran Canaria: A cross-sectional study].
AB  - OBJECTIVE: To estimate the effect of the influenza vaccination in Primary
      Healthcare workers and the general population vaccinated during the 2015/2016
      campaign. DESIGN: Cross-sectional study. SETTING: All the Primary Healthcare
      centres within the Gran Canaria healthcare region. PARTICIPANTS: A total of 1,868
      Primary Healthcare workers (33.5% men; 66.5% women) and 795,605 individuals from
      the general population (49.4% men; 50.6% women). PRINCIPAL MEASUREMENTS: The
      outcome variables in Primary Healthcare workers were: influenza cases reported to
      the Epidemiological Surveillance System, and the sick leave days due to illness.
      In the general population: reported flu cases and vaccination coverage in
      connection with the vaccination status of the healthcare professional. The
      magnitude of association between vaccination and morbidity was estimated applying
      logistic regression models. RESULTS: Although not statistically significant,
      healthcare professionals that were not vaccinated had 1.7-fold increase in the
      risk of having influenza than those vaccinated. In the general population the
      association was significant in the female population (OR: 1.3; 95%CI: 1.1-1.5).
      Population coverage was significantly higher when both the doctor and nurse were
      vaccinated (OR: 1.3; 95%CI: 1.3-1.3), and reported flu cases decreased when the
      nurse was vaccinated (OR: 0.9; 95%CI: 0.9-0.9). CONCLUSION: A possible protective
      effect of influenza vaccination was observed in the general population, as well
      as an influence of Primary Healthcare workers on the patients regarding this.
      Even so, the low coverages registered point to a need to implement measures that
      may lead to a more favourable attitude towards influenza vaccination.

PMID- 29656797
TI  - Approach and Management of Traumatic Retroperitoneal Injuries.
AB  - Traumatic retroperitoneal injuries constitute a challenge for trauma surgeons.
      They usually occur in the context of a trauma patient with multiple associated
      injuries, in whom invasive procedures have an important role in the diagnosis of
      these injuries. The retroperitoneum is the anatomical region with the highest
      mortality rates, therefore early diagnosis and treatment of these lesions acquire
      special relevance. The aim of this study is to present current published
      scientific evidence regarding incidence, mechanism of injury, diagnostic methods
      and treatment through a review of the international literature from the last 70
      years. In conclusion, this systematic review showed an increasing trend towards
      non-surgical management of retroperitoneal injuries.

PMID- 29656798
TI  - A Comparative study of two types of organ-sparing surgeries for early stage
      penile cancer: Wide local excision vs partial penectomy.
AB  - INTRODUCTION: Till date, there have been few reports of comparative studies on
      the outcomes of these different treatment modalities. In this study, we have
      aimed to comparatively evaluate the quality-of-life parameters, including sexual
      function, urinary function, and health-related quality of life (HRQOL), in
      patients with early stage penile cancers who underwent two different organ
      sparing surgeries. MATERIAL AND METHODS: From March 2012 to March 2015, we
      enrolled 15 patients with early stage penile cancers who underwent either wide
      local excision or partial penectomy as organ-sparing surgical treatments. We
      assessed their sexual and urinary functions and their HRQOL, using the
      International Index of Erectile Function (IIEF-15), Self-Esteem and Relationship
      (SEAR), and Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS)
      questionnaires and urodynamic determinations, and comparatively analyzed the
      outcomes of these patients who underwent either type of surgery. RESULTS: All
      patients who underwent these two types of surgeries experienced satisfactory
      outcomes. The patients who underwent wide local excision performed relatively
      better, in terms of their sexual functions, urinary functions, and HRQOL, but no
      statistically significant differences were observed in the data collected via the
      IIEF-15, SEAR, EDITS, and EORTC-QLQ-C30 questionnaires and urodynamic
      determinations (p > 0.05), except in the data corresponding to the orgasmic
      function (p = 0.033). CONCLUSION: Both types of organ-sparing surgeries assessed
      in this study achieved good outcomes, in terms of the aesthetics, sexual
      functions, urinary functions, and HRQOL in patients, without compromising the
      therapeutic effects of these surgeries. However, the observed decreases in
      orgasmic function will need to be addressed further.

PMID- 29656799
TI  - Long-term outcomes of laparoscopic versus open D3 dissection for stage II/III
      colon cancer: Results of propensity score analyses.
AB  - BACKGROUND: Non-inferiority of the laparoscopic approach for stage II/III colon
      cancer has not been clearly established. This study aimed to evaluate the long
      term outcomes of laparoscopic versus open D3 surgery. METHODS: Subjects were 1230
      consecutive patients with stage II/III colon cancer, who were referred to the
      National Cancer Center Hospital from 2004 to 2013. Open surgery was performed in
      821 (67%) patients, and laparoscopic surgery was performed in 409 (33%).
      Propensity score analyses with overall survival as the primary endpoint were
      performed in three different propensity score methods. RESULTS: Regression
      adjustment using the propensity score as a linear predictor in the model showed
      similar overall survival between laparoscopic and open surgeries [hazard ratio
      (HR), 0.98 (95% CI [0.64-1.46]; p = 0.916)]. Stratification analysis of the
      entire cohort revealed that, among five strata, only the highest stratum
      (clinical T2/T3, clinical N0/N1, tumor size <6 cm, and body mass index (BMI) <
      28) had an HR of <1 (0.37). In the other four strata, open surgery was favored as
      reflected by HRs of >1 (1.13-1.26). The propensity score-matched cohort (365
      matched pairs), from which patients with advanced disease and high BMI were
      excluded, yielded an HR of 0.93 (95% CI [0.57-1.52]; p = 0.772). CONCLUSIONS:
      Laparoscopic surgery appeared to be a safe and reasonable option for patients
      with stage II/III colon cancer in general. Patients with high BMI, clinical N2
      and T4 disease, and tumor size >=6 cm might require prudent selection of surgical
      approach.

PMID- 29656800
TI  - Dopaminergic Disturbances in Tourette Syndrome: An Integrative Account.
AB  - Tourette syndrome (TS) is thought to involve dopaminergic disturbances, but the
      nature of those disturbances remains controversial. Existing hypotheses suggest
      that TS involves 1) supersensitive dopamine receptors, 2) overactive dopamine
      transporters that cause low tonic but high phasic dopamine, 3) presynaptic
      dysfunction in dopamine neurons, or 4) dopaminergic hyperinnervation. We review
      evidence that contradicts the first two hypotheses; we also note that the last
      two hypotheses have traditionally been considered too narrowly, explaining only
      small subsets of findings. We review all studies that have used positron emission
      tomography and single-photon emission computerized tomography to investigate the
      dopaminergic system in TS. The seemingly diverse findings from those studies have
      typically been interpreted as pointing to distinct mechanisms, as evidenced by
      the various hypotheses concerning the nature of dopaminergic disturbances in TS.
      We show, however, that the hyperinnervation hypothesis provides a simple,
      parsimonious explanation for all such seemingly diverse findings. Dopaminergic
      hyperinnervation likely causes increased tonic and phasic dopamine. We have
      previously shown, using a computational model of the role of dopamine in basal
      ganglia, that increased tonic dopamine and increased phasic dopamine likely
      increase the propensities to express and learn tics, respectively. There is
      therefore a plausible mechanistic link between dopaminergic hyperinnervation and
      TS via increased tonic and phasic dopamine. To further bolster this argument, we
      review evidence showing that all medications that are effective for TS reduce
      signaling by tonic dopamine, phasic dopamine, or both.

PMID- 29656801
TI  - [The law of March 5, 2007 and the care of persons placed under guardianship].
AB  - The care of persons placed under guardianship has changed considerably since the
      law of March 5, 2007, as greater autonomy is granted to them. By advocating
      greater autonomy of protected adults, the French Civil Code is in opposition with
      the French Public Health Code since the latter states that the systematic consent
      of the guardian is required in addition to that of the protected adult for so
      called general care. In cases of serious injury to bodily integrity, the
      guardianship judge's opinion must be sought by the guardian. For some specific
      medical procedures (medically assisted procreation, abortion, etc.), the consent
      of the guardian does not seem necessary. A protected adult can now, if he/she is
      able to understand the information, with the agreement of the guardianship judge
      or the family council, appoint a trusted person and draft advance directives
      without possible representation by the guardian. The legislator promotes greater
      autonomy while not neglecting their protection. It also helps relieve the
      guardian, who is generally trained in asset management, of sometimes difficult
      medical decisions. Harmony between the Civil Code and the Public Health Code
      seems essential so as to move towards greater autonomy of the person under
      guardianship in the care relationship.

PMID- 29656802
TI  - Impact on the brain of the inflammatory response to surgery.
AB  - The brain is both the orchestrator as well as the target of the innate immune
      system's response to the aseptic trauma of surgery. When trauma-induced
      inflammation is not appropriately regulated persistent neuro-inflammation
      interferes with the synaptic plasticity that underlies the learning and memory
      aspects of cognition. The complications that ensue, include postoperative
      delirium (POD) and postoperative cognitive dysfunction (POCD) at two poles of a
      constellation that is now termed perioperative neurocognitive disorders. While
      the relationship of acute POD to the more indolent POCD is not completely
      understood both can be further complicated by earlier-onset of dementia and
      higher mortality. How and why these disorders occur is the focus of this report.
      The innate immune system response to peripheral trauma signals to the brain
      through a regulated cascade of cellular and molecular actors producing a
      teleological defense mechanism, "sickness behavior," to curtail further injury
      and initiate repair. Sickness behavior, including disordered cognition, is
      terminated by neural and humoral pathways that restore homeostasis and launch the
      organism on a path to good health. With so many "moving parts" the innate immune
      system is vulnerable in clinical settings that include advanced age and lifestyle
      induced diseases such as "unhealthy" obesity and the inevitable insulin
      resistance. Under these conditions, inflammation may become exaggerated and long
      lived. Consideration is provided how to identify the high-risk surgical patient
      and both pharmacological (including biological compounds) and non-pharmacological
      strategies to customize care.

PMID- 29656803
TI  - ?

PMID- 29656804
TI  - Tools to screen and measure cognitive impairment after surgery and anesthesia.
AB  - Cognition is essential to all aspects of our everyday life. Although we take our
      cognitive function for granted, the perioperative period is prone to several
      aggressions that might impair it. Postoperative cognitive dysfunction, has been
      the aim of many studies recently, and was shown to be very common with an
      incidence that can reach 40%, yielding not only impairment in cognition, but also
      longer hospital stays, higher costs and greater mortality. While several studies
      have revealed some of the mechanisms contributing to postoperative cognitive
      dysfunction, the search for the perfect instrument to screen and measure
      cognitive (dys)function has proven more elusive. The present paper aims to review
      several cognitive evaluation methods, discussing their advantages and
      disadvantages as well as their potential clinical applications in evaluating the
      dynamics of the recovery of cognitive function after anesthesia and surgery. The
      current availability of easy to use computerized tests might provide the tools
      necessary to identify patients at risk, and promptly provide them with the
      adequate course of action.

PMID- 29656805
TI  - Multiple opioid prescriptions among privately insured dental patients in the
      United States: Evidence from claims data.
AB  - BACKGROUND: Multiple or high dosage opioid prescriptions increase the risk of
      experiencing drug misuse and overdose. The authors examine index (first) and
      follow-up opioid prescriptions for 1 year among privately insured dental patients
      in the United States from 2010 through 2015. METHODS: The authors used the 2010
      through 2015 Truven Health MarketScan Research databases and the Prescription
      Drug Monitoring Program Training Technical Assistance Center conversion data set.
      The authors analyzed index prescriptions, repeat prescriptions over 1 year, same
      day multiple prescriptions, and concurrent prescriptions among dental patients.
      Descriptive analyses were conducted for days' supply, quantity of opioids, daily
      morphine milligram equivalent (MME) dose, and total MME dose. RESULTS:
      Approximately 17.27% of all index prescriptions were dental related. The
      percentage of dental-related index prescriptions for age groups 11 through 18
      years and 19 through 25 years was 23.51% and 23.41%, respectively. Approximately
      80.87% of repeat prescriptions within 30 days of dental-related index
      prescriptions were dental related. In 39.07% of dental-related same-day multiple
      prescription incidents, the daily dose was greater than or equal to 50 MME.
      Approximately 58.28% of dental-related concurrent prescriptions were dispensed
      when an existing dental-related opioid prescription was available. CONCLUSIONS:
      Dental-related index prescriptions were highest for the age groups 11 through 18
      years and 19 through 25 years. The frequency of dental-related repeat
      prescriptions was the highest within 30 days of a dental-related index
      prescription. PRACTICAL IMPLICATIONS: Low dosages of opioids and the use of
      prescription drug monitoring programs before prescribing opioids may reduce the
      potential for drug misuse or overdose.

PMID- 29656806
TI  - Is social media the way to empower patients to share their experiences of dental
      care?
AB  - BACKGROUND: Social media present opportunities to understand patient experience
      and information needs. In this study, the authors use hypodontia as an example to
      explore social media use by dental patients and how this provides for
      understanding patient experience. METHODS: The cross-sectional survey design
      involved systematic search of 6 social media online environments with hypodontia
      related terms. The authors categorized records by using a coding system for user,
      type and theme of post, and target audience. The authors used a thematic
      framework approach to analyze qualitatively the word content of posts from people
      affected by hypodontia (nondentists). RESULTS: The authors searched and
      identified 571 records and included 467 of them in their study. The authors
      analyzed the content of records from people affected by hypodontia (n = 176).
      Themes emerged about the experience of untreated hypodontia, treatment experience
      and outcomes, and decision making. Content analysis provided evidence about peer
      to-peer communication, areas of information need, and desire for peer support.
      CONCLUSIONS: Social media communities have responded to the need for information
      exchange and peer support by the public. Analysis of communications helped
      identify a need for dissemination of understandable information to patients and
      improved dentist awareness of patient needs. PRACTICAL IMPLICATIONS: Clinicians
      should reassess understanding and information needs actively throughout treatment
      and identify support needs. Clinicians should refer patients to quality
      information sources and peer support groups.

PMID- 29656807
TI  - The importance of the history and clinical examination.

PMID- 29656808
TI  - Injections for Knee Osteoarthritis: Corticosteroids, Viscosupplementation,
      Platelet-Rich Plasma, and Autologous Stem Cells.
AB  - This article reviews the benefits of corticosteroid, viscosupplementation,
      platelet-rich plasma, and autologous mesenchymal stem cell injections for the
      treatment of patients with knee osteoarthritis. Integrating injections into both
      clinical and surgical practices is complicated given existing health insurance
      reimbursement policies. This review describes the outcomes associated with these
      interventions and appropriate methods of navigating the existing reimbursement
      pathways to help providers implement these treatments into their practices.

PMID- 29656809
TI  - Lateral Knee Compartment Portals: A Cadaveric Study Defining a Posterolateral
      Viewing Safety Zone.
AB  - PURPOSE: This study attempted to define a reproducible "safe zone" based on extra
      and intra-articular knee anatomy for placing one or 2 accessory portals in the
      lateral tibiofemoral compartment for posterolateral region viewing. METHODS:
      Standard portals were created in 10 cadaveric knees to enable posterolateral
      region arthroscopic lateral tibiofemoral joint compartment viewing. After
      identifying the lateral knee surface tissue "soft spot," an accessory
      posterolateral portal (A) was created using an 18-gauge spinal needle and 4-mm
      cannula under direct visualization of a 70 degrees  arthroscope through the
      anteromedial portal. A second accessory portal (B) was then created 1 cm
      posterior and 1 cm superior to portal A. Accessory portal locations were measured
      relative to capsular fold and popliteus tendon locations. Distances from the
      peroneal nerve, lateral collateral ligament, popliteus tendon, and the biceps
      tendon were determined. Statistical analysis compared portal location differences
      from key anatomical structures (P < .05). RESULTS: Accessory portal A (mean +/-
      95% confidence interval) was located 8.8 +/- 2.7 mm from the popliteus tendon,
      11.6 +/- 2.7 mm from the lateral collateral ligament (LCL), 26.8 +/- 2.3 mm from
      the peroneal nerve, and 4.9 +/- 2.5 mm from the biceps tendon. Accessory portal B
      was located 17.3 +/- 2.8 mm from the popliteus tendon, 20 +/- 2.8 mm from the
      LCL, 30.3 +/- 3.3 mm from the peroneal nerve, and 7.0 +/- 4.8 mm from the biceps
      tendon. Accessory portal B was located a greater distance from the LCL and the
      popliteus tendon than portal A (P < .0001). CONCLUSIONS: Using intra- and extra
      articular anatomic landmarks, both accessory portals could be safely placed in
      the lateral tibiofemoral joint compartment to enable posterolateral region
      viewing. Accessory portals used individually or in combination may enable easier
      posterolateral region viewing for arthroscopic repair of lateral tibiofemoral
      compartment structures. CLINICAL RELEVANCE: Lateral tibiofemoral compartment
      portals can be safely created to enable improved visibility for complex
      arthroscopic procedures in the posterolateral viewing region.

PMID- 29656810
TI  - The optimal sternal closure technique: Still elusive.

PMID- 29656811
TI  - Discussion.

PMID- 29656812
TI  - Seeking the greatest value of our action.

PMID- 29656813
TI  - Ask not what your Fontan can do for you, ask what you can do for your Fontan!

PMID- 29656814
TI  - Flow equals grow? Dunno!

PMID- 29656815
TI  - Adherence to lung cancer surgical quality standards is critical for the survival
      of both our patients and our specialty.

PMID- 29656816
TI  - The devil is in the details.

PMID- 29656817
TI  - Saving the esophagus: At what cost?

PMID- 29656818
TI  - The aortic root does not dilate over time after replacement of the aortic valve
      and ascending aorta in patients with bicuspid or tricuspid aortic valves.
AB  - OBJECTIVE: Whether the aortopathy associated with bicuspid aortic valve (BAV)
      disease occurs secondary to genetic or hemodynamic factors remains controversial.
      In this article we describe the natural history of the aortic root in patients
      with bicuspid versus tricuspid aortic valves (TAVs) after replacement of the
      aortic valve and ascending aorta. METHODS: From 1990 to 2010, 406 patients (269
      BAV, 137 TAV) underwent aortic valve and ascending aorta replacement at a single
      institution. Patients with aortic dissection, endocarditis, previous aortic
      surgery, or Marfan syndrome were excluded. All available follow-up imaging was
      reviewed. RESULTS: Mean imaging follow-up was 5.5 (+/-5.3) years. Of all
      patients, 66.5% had at least 1 aortic root measurement after the index operation.
      Baseline aortic diameter was comparable between groups. In patients with BAV,
      aortic root diameter increased at a clinically negligible rate over time (0.654
      mm per year; 95% confidence interval, 0.291-1.016; P < .001), similar to patients
      with TAV (P = .92). Mean clinical follow-up was 8.1 (+/-5.4) years. During follow
      up, 18 patients underwent reoperation, 89% for a degenerated bioprosthetic aortic
      valve. Only 1 patient underwent reoperation for a primary indication of aortic
      aneurysmal disease, 22 years after the index operation. There were no differences
      in cumulative incidence rates of aortic reoperation (P = .14) between patients
      with BAV and TAV. CONCLUSIONS: Mid-term imaging after aortic valve and ascending
      aorta replacement indicates that if the aortic root is not dilated at the time of
      surgery, the risk of enlargement over time is minimal, negating the need for
      prophylactic root replacement in patients with BAV or TAV.

PMID- 29656819
TI  - The search for reliable markers of ground glass opacity prognosis: The truth
      remains largely unknown.

PMID- 29656820
TI  - Wall stress on ascending thoracic aortic aneurysms with bicuspid compared with
      tricuspid aortic valve.
AB  - OBJECTIVE: Guidelines for repair of bicuspid aortic valve-associated ascending
      thoracic aortic aneurysms have been changing, most recently to the same criteria
      as tricuspid aortic valve-ascending thoracic aortic aneurysms. Rupture/dissection
      occurs when wall stress exceeds wall strength. Recent studies suggest similar
      strength of bicuspid aortic valve versus tricuspid aortic valve-ascending
      thoracic aortic aneurysms; thus, comparative wall stress may better predict
      dissection in bicuspid aortic valve versus tricuspid aortic valve-ascending
      thoracic aortic aneurysms. Our aim was to determine whether bicuspid aortic valve
      ascending thoracic aortic aneurysms had higher wall stresses than their tricuspid
      aortic valve counterparts. METHODS: Patients with bicuspid aortic valve- and
      tricuspid aortic valve-ascending thoracic aortic aneurysms (bicuspid aortic valve
      = 17, tricuspid aortic valve = 19) greater than 4.5 cm underwent
      electrocardiogram-gated computed tomography angiography. Patient-specific 3
      dimensional geometry was reconstructed and loaded to systemic pressure after
      accounting for prestress geometry. Finite element analyses were performed using
      the LS-DYNA solver (LSTC Inc, Livermore, Calif) with user-defined fiber-embedded
      material model to determine ascending thoracic aortic aneurysm wall stress.
      RESULTS: Bicuspid aortic valve-ascending thoracic aortic aneurysms 99th
      percentile longitudinal stresses were 280 kPa versus 242 kPa (P = .028) for
      tricuspid aortic valve-ascending thoracic aortic aneurysms in systole. These
      stresses did not correlate to diameter for bicuspid aortic valve-ascending
      thoracic aortic aneurysms (r = -0.004) but had better correlation to tricuspid
      aortic valve-ascending thoracic aortic aneurysms diameter (r = 0.677).
      Longitudinal stresses on sinotubular junction were significantly higher in
      bicuspid aortic valve-ascending thoracic aortic aneurysms than in tricuspid
      aortic valve-ascending thoracic aortic aneurysms (405 vs 329 kPa, P = .023).
      Bicuspid aortic valve-ascending thoracic aortic aneurysm 99th-percentile
      circumferential stresses were 548 kPa versus 462 kPa (P = .033) for tricuspid
      aortic valve-ascending thoracic aortic aneurysms, which also did not correlate to
      bicuspid aortic valve-ascending thoracic aortic aneurysm diameter (r = 0.007).
      CONCLUSIONS: Circumferential and longitudinal stresses were greater in bicuspid
      aortic valve- than tricuspid aortic valve-ascending thoracic aortic aneurysms and
      were more pronounced in the sinotubular junction. Peak wall stress did not
      correlate with bicuspid aortic valve-ascending thoracic aortic aneurysm diameter,
      suggesting diameter alone in this population may be a poor predictor of
      dissection risk. Our results highlight the need for patient-specific aneurysm
      wall stress analysis for accurate dissection risk prediction.

PMID- 29656821
TI  - Is less really more? Endoscopic mucosal resection versus esophagectomy for
      submucosal esophageal adenocarcinoma.

PMID- 29656822
TI  - Metabolite Depletion Affects Flux Profiling of Cell Lines.
AB  - Quantifying the rate of consumption and release of metabolites (i.e., flux
      profiling) has become integral to the study of cancer. The fluxes as well as the
      growth of the cells may be affected by metabolite depletion during cultivation.

PMID- 29656823
TI  - "Association splitting" versus cognitive remediation in obsessive-compulsive
      disorder: A randomized controlled trial.
AB  - Studies have confirmed the efficacy of the cognitive intervention Association
      Splitting (AS) in obsessive-compulsive disorder (OCD) when applied as a self-help
      technique. AS aims to alter symptom-provoking automated cognitive networks of OC
      related stimuli by building new or strengthening established but weak neutral
      associations. The aim of this study was to investigate the acceptance and
      benefits of therapist-assisted AS as an add-on to cognitive behavioral therapy
      (CBT). One hundred and nine patients with OCD who were undergoing CBT were
      randomly assigned to either AS or cognitive remediation (CR). Both groups were
      assessed at baseline, 4 weeks and 6 months later. The primary measure was the
      Yale-Brown Obsessive Compulsive Scale. Although patients' acceptance of AS was
      good, AS was not better than CR regarding overall symptom severity. However, a
      larger decrease was found from baseline to 6 months follow-up in AS regarding
      avoidance. Moreover, subsidiary analyses excluding control patients who had
      obtained information about AS indicated its superiority. Because superiority of
      AS was found in post hoc analyses excluding control patients who had obtained
      information on AS, we suggest that contagion effects deserve consideration.

PMID- 29656824
TI  - Ductus arteriosus aneurysm: Case report and review of the literature.
AB  - We report the case of an infant boy born at 39 weeks and 5 days who presented a
      cleft lip and palate. During the assessment to detect associated malformations,
      cardiac auscultation revealed a systolic heart murmur. Echocardiography and
      subsequent thoracic computed tomography angiography identified an aneurysm of the
      ductus arteriosus. Ductus arteriosus aneurysm, a complicated form of patent
      ductus arteriosus, may not be as rare as once considered. A clear majority of
      ductus arteriosus aneurysms are asymptomatic and physiologically resolve after
      birth. Nevertheless, severe complications can occur, primarily during the
      postnatal period.

PMID- 29656825
TI  - Parenteral nutrition for preterm infants: Issues and strategy.
AB  - Due to transient gut immaturity, most very preterm infants receive parenteral
      nutrition (PN) in the first few weeks of life. Yet providing enough protein and
      energy to sustain optimal growth in such infants remains a challenge.
      Extrauterine growth restriction is frequently observed in very preterm infants at
      the time of discharge from hospital, and has been found to be associated with
      later impaired neurodevelopment. A few recent randomized trials suggest that
      intensified PN can improve early growth; whether or not such early PN improves
      long-term neurological outcome is still unclear. Several other questions
      regarding what is optimal PN for very preterm infants remain unanswered. Amino
      acid mixtures designed for infants contain large amounts of branched-chain amino
      acids and taurine, but there is no consensus on the need for some nonessential
      amino acids such as glutamine, arginine, and cysteine. Whether excess growth in
      the first few weeks of life, at a time when very preterm infants receive PN, has
      an imprinting effect, increasing the risk of metabolic or vascular disease at
      adulthood continues to be debated. Even though uncertainty remains regarding the
      long-term effect of early PN, it appears reasonable to propose intensified
      initial PN. The aim of the current position paper is to review the evidence
      supporting such a strategy with regards to the early phase of nutrition, which is
      mainly covered by parenteral nutrition. More randomized trials are, however,
      needed to further support this type of approach and to demonstrate that this
      strategy improves short- and long-term outcome.

PMID- 29656827
TI  - [Primary congenital glaucoma neglected: Still a cause of low vision in children
      in Morocco].

PMID- 29656826
TI  - Changes in conditions at birth in France from 1995 to 2016: Results of the
      National Perinatal Surveys.

PMID- 29656828
TI  - [Ophthalmological presentation of hypertensive crisis in the context of Berger's
      disease: Recommendation for a multidisciplinary follow-up of IgA nephropathies].

PMID- 29656829
TI  - [Uveitis treated with biotherapy and/or DMARD: Analysis from the French
      Pharmacovigilance Study Base].
AB  - PURPOSE: To report the characteristics of uveitis cases occurring while on
      biologic therapy or disease-modifying antirheumatic drugs (DMARDs) reported to
      the French national pharmacovigilance database. METHODS: All the uveitis cases
      occurring in patients with chronic rheumatologic diseases, chronic inflammatory
      intestinal diseases or connective tissue diseases, while treated with DMARDs
      and/or biologic therapies between 2000 and 2015 and reported to the French
      National Pharmacovigilance Database were collected. RESULTS: During the study
      period, 32 cases of uveitis were reported (15 men, 17 women). Two patients were
      treated with one DMARD alone, 24 with biologic therapy alone, and six with both
      treatments. Anterior uveitis was diagnosed in 19 patients (8 cases were
      bilateral); intermediate uveitis was found (unilaterally) in one patient;
      posterior and diffuse uveitis occurred in 5 and 2 cases respectively. Five cases
      were inconclusive with regard to the anatomical type of uveitis. The uveitis was
      of infectious origin in 5 cases: 2 toxoplasmosis, 2 herpes virus and 1
      tuberculosis. In the 27 other cases, it was not possible to state whether the
      uveitis was associated with the underlying disease (uncontrolled) or a side
      effect of the biologic/DMARD treatments. The occurrence of the uveitis led to 9
      switches in biologic therapy and 13 discontinuations of treatment (8 complete
      discontinuations, 5 discontinuations only until uveitis remission was obtained).
      In 4 cases, the treatments were not modified. The database does not specify the
      ultimate course or rheumatologic disease activity at the time of the uveitis.
      CONCLUSIONS: The presence of uveitis while on biologic therapy must not be taken
      to indicate a therapeutic failure, especially if the ocular manifestation is
      isolated. In the case of uveitis occurring in patients treated with biologic
      therapies and/or DMARDs, infectious complications should be ruled out.

PMID- 29656830
TI  - Cairo consensus on the IVF laboratory environment and air quality: report of an
      expert meeting.
AB  - This proceedings report presents the outcomes from an international Expert
      Meeting to establish a consensus on the recommended technical and operational
      requirements for air quality within modern assisted reproduction technology (ART)
      laboratories. Topics considered included design and construction of the facility,
      as well as its heating, ventilation and air conditioning system; control of
      particulates, micro-organisms (bacteria, fungi and viruses) and volatile organic
      compounds (VOCs) within critical areas; safe cleaning practices; operational
      practices to optimize air quality while minimizing physicochemical risks to
      gametes and embryos (temperature control versus air flow); and appropriate
      infection-control practices that minimize exposure to VOC. More than 50 consensus
      points were established under the general headings of assessing site suitability,
      basic design criteria for new construction, and laboratory commissioning and
      ongoing VOC management. These consensus points should be considered as
      aspirational benchmarks for existing ART laboratories, and as guidelines for the
      construction of new ART laboratories.

PMID- 29656831
TI  - Corrigendum to miR144-3p inhibits PMVECs excessive proliferation in angiogenesis
      of hepatopulmonary syndrome via Tie2 [Exp. Cell Res. 365 (2018) 24-32].

PMID- 29656832
TI  - Is there a role for iron supplementation in critically ill patients?

PMID- 29656833
TI  - A Highly Sensitive and Robust Method for Hepatitis B Virus Covalently Closed
      Circular DNA Detection in Single Cells and Serum.
AB  - Despite implications of persistence of hepatitis B virus (HBV) covalently closed
      circular DNA (cccDNA) in the development of hepatocellular carcinoma (HCC),
      little is known about serum cccDNA in HBV-infected diseases. We developed a
      cccDNA-selective droplet digital PCR (ddPCR) to assess cccDNA content and
      dynamics across different stages of HCC development. One hundred forty-seven
      serum samples and 35 formalin-fixed, paraffin-embedded tumor tissues were derived
      from patients with HCC or HBV hepatitis/cirrhosis. After specific amplification
      and selective digestion, probe-based ddPCR was used to quantify cccDNA copy
      numbers in single cells and clinical samples. The cccDNA in single HepG2.2.15
      cells ranged from 0 to 10.8 copies/cell. Compared with non-HCC patients, HCC
      patients showed a higher cccDNA-positive rate (89.9% versus 53.2%; P = 4.22 * 10
      6) and increased serum cccDNA contents (P = 0.002 and P = 0.041 for hepatitis and
      cirrhosis patients, respectively). Serum cccDNA ranged from 84 to 1.07 * 105
      copies/mL. Quantification of serum cccDNA and HBV-DNA was an effective way to
      discriminate HCC patients from non-HCC patients, with areas under the curve of
      receiver operating characteristic of 0.847 (95% CI, 0.759-0.935; sensitivity,
      74.5%; specificity, 93.7%). cccDNA-selective ddPCR is sensitive to detect cccDNA
      in single cells and different clinical samples. Combined analysis of serum cccDNA
      and HBV-DNA may be a promising strategy for HBV-induced HCC surveillance and
      antiviral therapy evaluation.

PMID- 29656834
TI  - Controlling ticks and tick-borne diseases...looking forward.
AB  - Tick-borne diseases (TBDs) represent a growing burden for human and animal health
      worldwide. Several approaches including the use of chemicals with repellency and
      parasiticidal activity, habitat management, genetic selection of hosts with
      higher resistance to ticks, and vaccines have been implemented for reducing the
      risk of TBDs. However, the application of latest gene editing technologies in
      combination with vaccines likely combining tick and pathogen derived antigens and
      other control measures should result in the development of effective, safe, and
      environmentally sound integrated control programs for the prevention and control
      of TBDs. This paper is not a review of current approaches for the control of
      ticks and TBDs, but an opinion about future directions in this area.

PMID- 29656835
TI  - Trauma Quality Improvement: Reducing Triage Errors by Automating the Level
      Assignment Process.
AB  - BACKGROUND: Trauma patients are triaged by the severity of their injury or need
      for intervention while en route to the trauma center according to trauma
      activation protocols that are institution specific. Significant research has been
      aimed at improving these protocols in order to optimize patient outcomes while
      striving for efficiency in care. However, it is known that patients are often
      undertriaged or overtriaged because protocol adherence remains imperfect. The
      goal of this quality improvement (QI) project was to improve this adherence, and
      thereby reduce the triage error. It was conducted as part of the formal
      undergraduate medical education curriculum at this institution. STUDY DESIGN: A
      QI team was assembled and baseline data were collected, then 2 Plan-Do-Study-Act
      (PDSA) cycles were implemented sequentially. During the first cycle, a novel web
      tool was developed and implemented in order to automate the level assignment
      process (it takes EMS-provided data and automatically determines the level); the
      tool was based on the existing trauma activation protocol. The second PDSA cycle
      focused on improving triage accuracy in isolated, less than 10% total body
      surface area burns, which we identified to be a point of common error. Traumas
      were reviewed and tabulated at the end of each PDSA cycle, and triage accuracy
      was followed with a run chart. SETTING: This study was performed at Vanderbilt
      University Medical Center and Medical School, which has a large level 1 trauma
      center covering over 75,000 square miles, and which sees urban, suburban, and
      rural trauma. PARTICIPANTS: The baseline assessment period and each PDSA cycle
      lasted 2 weeks. During this time, all activated, adult, direct traumas were
      reviewed. There were 180 patients during the baseline period, 189 after the first
      test of change, and 150 after the second test of change. All were included in
      analysis. RESULTS: Of 180 patients, 30 were inappropriately triaged during
      baseline analysis (3 undertriaged and 27 overtriaged) versus 16 of 189 (3
      undertriaged and 13 overtriaged) following implementation of the web tool (p =
      0.017 for combined errors). Overtriage dropped further from baseline to 10/150
      after the second test of change (p = 0.005). The total number of triaged patients
      dropped from 92.3/week to 75.5/week after the second test of change. There was no
      statistically significant change in the undertriage rate. CONCLUSION: The
      combination of web tool implementation and protocol refinement decreased the
      combined triage error rate by over 50% (from 16.7%-7.9%). We developed and tested
      a web tool that improved triage accuracy, and provided a sustainable method to
      enact future quality improvement. This web tool and QI framework would be easily
      expandable to other hospitals.

PMID- 29656836
TI  - Modulating Effect of Contextual Factors on Factor Structure and Reliability of
      SARC-F.

PMID- 29656837
TI  - Long-term Care Status in Centenarians and Younger Cohorts of Oldest Old in the
      Last 6 Years of Life: Trajectories and Potential Mechanisms.
AB  - OBJECTIVES: A large proportion of the oldest old and centenarians live in long
      term care facilities. Although there may be distinct care patterns in
      centenarians compared with other cohorts of oldest old, the exact development
      concerning prevalence, length of stay, and factors that are associated with long
      term care status in the last years before death is unknown. DESIGN: Longitudinal
      analyses of health insurance data across 6 years before death. SETTING AND
      PARTICIPANTS: In all, 1398 institutionalized and noninstitutionalized oldest old
      [deceased at 80-89 (octogenarians), 90-99 (nonagenarians), or over 100 years of
      age (centenarians)] from Germany were included. Long-term care status and
      transition from home care into long-term care over 6 years (34,740 person
      quarters). MEASUREMENTS: Dementia, musculoskeletal diseases, multimorbidity,
      hospital admission, gender, and age at death were derived from administrative
      data and analyzed using binary generalized estimating equations. RESULTS:
      Although the initial level of long-term care (6 years before death) was higher
      among centenarians (65.1% vs 53.6% in nonagenarians; 36.2% in octogenarians), the
      rate of increase was stronger in the younger cohorts. Distinguishing between long
      term care escapers, delayers, and survivors, the proportion of those who escaped,
      delayed, or survived the entire 6 years of observation in long-term care was
      33.4%/40.4%/26.2% in centenarians, 45.0%/45.1%/9.9% in nonagenarians, and
      62.7%/33.7%/3.6% in octogenarians. Age, hospital admissions, and dementia were
      positively associated with being in long-term care, whereas musculoskeletal
      disorders were negatively associated with long-term care. The association with
      dementia was significantly weaker in centenarians. CONCLUSIONS: For centenarians,
      although they are more often in long-term care, the transition rate to long-term
      care progressed more slowly than the rates of the younger comparison cohorts of
      oldest old. The high proportion of long stays of centenarians in long-term care
      facilities require different concepts of long-term care.

PMID- 29656838
TI  - Does Cognitive Impairment and Agitation in Dementia Influence Intervention
      Effectiveness? Findings From a Cluster-Randomized-Controlled Trial With the
      Therapeutic Robot, PARO.
AB  - OBJECTIVES: To explore whether severity of cognitive impairment and agitation of
      older people with dementia predict outcomes in engagement, mood states, and
      agitation after a 10-week intervention with the robotic seal, PARO. DESIGN: Data
      from the PARO intervention-arm of a cluster-randomized controlled trial was used,
      which involved individual, nonfacilitated, 15-minute sessions with PARO 3
      afternoons per week for 10 weeks. SAMPLE AND PARTICIPANTS: One hundred thirty
      eight residents-aged >=60 years, with dementia-from 9 long-term care facilities.
      MEASURES: A series of stepwise multiple linear regressions were conducted.
      Dependent variables were participants' levels of engagement, mood states, and
      agitation at week 10 [assessed by video observation and Cohen Mansfield Agitation
      Inventory-Short Form (CMAI-SF)]. Predictor variables were baseline levels of
      cognitive impairment [assessed by Rowland Universal Dementia Assessment Scale
      (RUDAS)] and agitation (CMAI-SF). RESULTS: Five models were produced. The
      strongest finding was that participants with more severe agitation at baseline
      had higher levels of agitation at week 10 (R2 = .82, P < .001). Predictors of
      positive response were less significant. Low levels of agitation at baseline
      predicted greater positive behavioral engagement with PARO (R2 = .054, P = .009)
      and fewer observed instances of agitation (R2 = .033, P = .045) at week 10,
      whereas greater visual engagement was predicted by both lower levels of agitation
      and cognitive impairment (R2 = .082, P = .006). Less severe cognitive impairment
      predicted greater pleasure at week 10 (R2 = .067, P = .004).
      CONCLUSIONS/IMPLICATIONS: Participants with severe agitation had poor response to
      PARO. Lower levels of agitation and higher cognitive functioning were associated
      with better responses. In clinical practice, we recommend PARO should be
      restricted to people with low-moderate severity of agitation. Further research is
      needed to determine the optimal participant characteristics for response to PARO.

PMID- 29656839
TI  - Identifying and Supporting Nonpharmacological Dementia Interventions Ready for
      Pragmatic Trials: Results From an Expert Workshop.

PMID- 29656840
TI  - An unforeseen complication of a folk remedy for joint pain.

PMID- 29656841
TI  - From phaeohyphomycosis to disseminated chromoblastomycosis: A retrospective study
      of infections caused by dematiaceous fungi.
AB  - OBJECTIVE: Infections caused by dematiaceous fungi are more common in tropical
      and subtropical areas. We aimed to describe the clinical, microbiological and
      therapeutic aspects of case patients diagnosed at a University Hospital located
      on an Indian Ocean island. PATIENTS AND METHODS: We performed an observational
      retrospective study of infections caused by dematiaceous fungi diagnosed at the
      University Hospital of Saint-Pierre, Reunion, from 2000 to 2015. Mycological
      identifications were performed at the National Reference Center for Invasive
      Mycosis and Antifungal Agents (Paris). RESULTS: The review of clinical and
      microbiological data of 11 patients identified revealed that five were infected
      by dematiaceous fungi. Two had cutaneous phaeohyphomycosis, two had cerebral
      phaeohyphomycosis and one had cutaneous chromoblastomycosis with brain and
      potentially medullary dissemination. Skin lesions and cerebral abscesses were
      quite varied. CONCLUSION: Infections caused by dematiaceous fungi are rare.
      Medullary and brain localizations are extremely rare, especially for
      chromoblastomycosis. Cutaneous manifestations of phaeohyphomycosis are varied;
      diagnosis is thus more difficult. It is therefore important, when confronted with
      a chronic tumor-like lesion in endemic areas, to perform a biopsy for pathology
      and fungal culture. While surgical excision is not always sufficient, medical
      treatment of these infections is not standardized, but relies on an azole, which
      can be associated with another antifungal agent.

PMID- 29656842
TI  - Incidence of all-cause adult community-acquired pneumonia in primary care
      settings in France.
AB  - OBJECTIVES: To estimate the incidence of all-cause outpatient community-acquired
      pneumonia (CAP) in adults in France from a national prospective observational
      study of CAP management in general practice (CAPA). METHODS: Patients aged over
      18 years presenting with signs or symptoms indicative of CAP associated with
      recent onset of unilateral crackles on auscultation and/or a new opacity on chest
      X-ray were included in the CAPA study. An ancillary survey (AIMSIS) aiming at
      identifying family physicians' difficulties in including patients and at
      collecting their opinion on the use of an electronic case report form, determined
      the number of non-included eligible patients. A three-step analysis was then
      performed, including computation of the total number of eligible patients,
      adjustment for seasonality, and extrapolation to the French FP population using
      indirect standardization to adjust for differences in characteristics between
      CAPA FPs and French FPs. RESULTS: Between September 2011 and July 2012, 267 (63%)
      CAPA investigators included 886 CAP patients. Most patients presented with mild
      CAP. The rates of hospitalization and one-month case fatality were 7% and 0.3%,
      respectively. Data from 336 (79%) AIMSIS investigators identified 641 additional
      patients and estimated at 234,023 the number of CAP patients per year (incidence
      of 4.7 per 1000 persons per year). CONCLUSIONS: Using a pragmatic case definition
      of CAP patients, this study estimated an incidence of 4.7 per 1000 persons per
      year that is in the lower half of the range of estimated incidences reported in
      primary care settings in industrialized countries.

PMID- 29656843
TI  - Erysipelothrix rhusiopathiae knee prosthesis infection.

PMID- 29656844
TI  - Association between cholesterol gallstones and testosterone replacement therapy
      in a patient with primary hypogonadism.
AB  - A 16-year-old boy had a past medical history of primary hypogonadism, due to
      bilateral anorchia. He presented with gallstones located in the gallbladder and a
      mild dilatation of the intrahepatic biliary tree. The histology study reported
      cholesterol gallstones. The patient had been treated with testosterone
      replacement therapy since infancy. We suggest a possible correlation between
      testosterone replacement therapy and the presence of cholesterol gallstones.

PMID- 29656845
TI  - Access to direct-acting antivirals for the treatment of hepatitis C in a country
      with limited resources.
AB  - AIMS: To estimate the number of patients that have access to treatment of
      hepatitis C with direct-acting antivirals in Argentina and evaluate the factors
      associated with the lack of access. MATERIALS AND METHODS: A cross-sectional
      cohort study was conducted that included all the consecutive prescriptions of
      direct-acting antivirals issued at health centers that participated in the ECHOTM
      telemedicine project directed by the Hospital Italiano de Buenos Aires, within
      the time frame of January 2016 and February 2017. RESULTS: A total of 143
      treatment prescriptions were included and overall access was 70% (95% CI 62-77%).
      The only independent factor associated with a lack of treatment access was
      coverage by a public healthcare system (OR 4.98 [95% CI 2.05- 12.09]).
      CONCLUSION: Patients with hepatitis C that were covered by a public healthcare
      system had a 4 times higher chance of not having access to treatment with direct
      acting antivirals than patients covered by other healthcare systems (private
      insurance or the social welfare system).

PMID- 29656846
TI  - Development and validation of a self-administered neck mobility assessment tool
      (S-ROM-Neck) in chronic neck pain patients.
AB  - BACKGROUND: Cervical spine (CS) range of motion (ROM) is commonly used to assess
      neck pain. However, this measurement is often limited by the clinician's
      experience and perception. Therefore, the integration of perceptual feedback of
      the patient can optimize and personalize treatment. OBJECTIVE: Develop and
      validate a questionnaire (S-ROM-Neck) to evaluate ROM of the CS from the
      patient's perspective. DESIGN: Validation study. METHODS: The assessment tool was
      developed and optimized during pretest sessions. Reliability and construct
      validity of the questionnaire were tested. 50 participants (age >18 years) with
      neck pain for >90 days, able to fluently speak, read, and write in German were
      included. Exclusion criteria included any condition that limited manual therapy
      to the CS. Participants completed S-ROM-Neck twice within seven days, along with
      the visual analogue scale (VAS) for pain intensity and the German version of the
      Neck Disability Index (NDI-G). The relative reliability, internal consistency,
      and absolute reliability were analyzed, and Bland-Altman plots were generated.
      Construct validity was established by correlating the total score of S-ROM-Neck
      with VAS and NDI-G based on pre-set hypotheses. RESULTS: S-ROM-Neck demonstrated
      moderate reliability with an intraclass correlation coefficient of 0.718
      (Cronbach's alpha of 0.83). There was a medium negative correlation between VAS
      and S-ROM-Neck [Spearman's rank correlation coefficient (rs) = -0.30, p = 0.031]
      and the NDI-G and S-ROM-Neck (rs = -0.40, p = 0.002). CONCLUSIONS: These results
      indicate the reliability and internal consistency of S-ROM-Neck. This scale
      provides patient feedback and perspectives to optimize assessment of neck pain.

PMID- 29656848
TI  - The discipline of epidemiology: engaging in the full breadth of population health
      science.
AB  - This address was delivered by Harold I. Feldman, MD, MSCE, at the Annual Meeting
      of the American College of Epidemiology in New Orleans, Louisiana, on September
      26, 2017. Dr. Feldman is George S. Pepper Professor of Public Health and
      Preventive Medicine, Professor of Epidemiology and Medicine, and Chair,
      Department of Biostatistics, Epidemiology, and Informatics at the Perelman School
      of Medicine at the University of Pennsylvania. He is recognized nationally and
      internationally for his expertise in kidney disease epidemiology. Dr. Feldman
      pioneered the integration of epidemiology and renal medicine with his first
      studies of dialyzer reuse and hemodialysis vascular access morbidity. He is
      internationally renowned in nephrology and clinical epidemiology and an architect
      of one of the largest and most successful epidemiological research programs in
      chronic kidney disease. For over 15 years, he has led NIH's Chronic Renal
      Insufficiency Cohort Study, placing him at the helm of the "Framingham Study of
      Renal Disease". It has elucidated the chronic kidney disease-specific
      relationships of mineral dysmetabolism and cardiovascular complications; dietary
      sodium and heart failure; novel vascular stiffness metrics and renal disease
      progression; cardiovascular biomarkers and heart failure; and cognitive decline
      and renal dysfunction, among others. He has also led the nation's largest trials
      targeting hemodialysis vascular access morbidity, discovered the benefits of
      transplantation before dialysis dependence, elucidated racial disparities and the
      role of genetics in kidney failure, and shaped our understanding of the toxicity
      from unregulated reuse of medical devices. He is the past President of the
      American College of Epidemiology and directs one of the nation's largest clinical
      epidemiology and biostatistics programs. Dr. Feldman has an MD from Boston
      University and an MSCE from the University of Pennsylvania. He is an elected
      member of the American Society of Clinical Investigation, the Association of
      American Physicians, and the American Epidemiological Society.

PMID- 29656847
TI  - The association between hardship and self-rated health: does the choice of
      indicator matter?
AB  - PURPOSE: The purpose of this study was to investigate the association between
      four specific forms of hardship (difficulty paying bills, ongoing financial
      stress, medication reduction due to cost, and food insecurity) and self-rated
      health among older men and women. METHODS: Cross-sectional logistic regression
      analysis was conducted using the 2010 wave of the Health and Retirement Study
      Leave-Behind Questionnaire (N = 7619) to determine the association between four
      hardship indicators and self-rated health. Hardship indicators (difficulty paying
      bills, ongoing financial stress, medication reduction due to cost, and food
      insecurity) were dichotomized (0 = no hardship, 1 = yes hardship) for this
      analysis. RESULTS: After adjusting for sociodemographic factors, participants
      reporting difficulty paying bills had an 1.8 higher odds of reporting poor self
      rated health (95% confidence intervals [CI]: 1.57, 2.15) and those reporting
      taking less medication due to cost had a 2.5 times higher odds of poor self-rated
      health (95% CI: 1.97, 3.09) compared to those not reporting these hardships. When
      stratified by gender, and adjusting for sociodemographic factors, men who took
      less medication due to cost had a 1.93 higher odds of low self-rated health (95%
      CI: 1.39, 2.67) and women who took less medications due to cost had a 2.9 higher
      odds of reporting poor self-rated health (95% CI: 2.23, 2.70) compared to women
      not reporting these hardships. CONCLUSIONS: Research in this area can provide
      greater conceptual and measurement clarity on the hardship experience and further
      elucidate the pathway between specific hardships and poor health outcomes to
      inform intervention development.

PMID- 29656849
TI  - Association of highly active antiretroviral treatment with incident tuberculosis
      in people living with HIV/AIDS.
AB  - PURPOSE: To determine the short-term and long-term effects of highly active
      antiretroviral therapy (HAART) on incident tuberculosis (TB) in people living
      with HIV/AIDS (PLWHA). METHODS: From 2000 to 2012, we identified adult PLWHA from
      Taiwan Centers for Disease Control HIV Surveillance System. All PLWHA were
      followed up until December 31, 2012, and observed for TB occurrence. Time
      dependent Cox proportional hazards models were used to determine the short-term
      and long-term effects of HAART on incident TB. RESULTS: Of 20,072 PLWHA, 628
      (3.13%) had incident TB, corresponding to an incident rate of 701/100,000 person
      years. After adjusting for potential confounders, PLWHA receiving HAART were more
      likely to develop TB than those not receiving the drugs (adjusted hazard ratio
      [AHR] 1.56; 95% confidence interval [CI] 1.18-2.05). While the short-term and
      long-term effects of HAART on incident TB were considered, HAART was a risk
      factor for TB development within the first 90 days (AHR 6.06; 95% CI 4.58-8.01)
      and between 90 and 180 days of treatment (AHR 1.80; 95% CI 1.11-2.94) but was a
      protective factor after 180 days of HAART use (AHR 0.51; 95% CI 0.39-0.66).
      CONCLUSIONS: HAART is a risk factor for the development of TB in the short term
      but a protective factor in the long term.

PMID- 29656850
TI  - Bradyrhizobium algeriense sp. nov., a novel species isolated from effective
      nodules of Retama sphaerocarpa from Northeastern Algeria.
AB  - We have characterized genetic, phenotypic and symbiotic properties of bacterial
      strains previously isolated from nitrogen-fixing nodules of Retama sphaerocarpa
      from Northern Algeria. Phylogenetic analyses of 16S rRNA genes and three
      concatenated housekeeping genes, recA, atpD and glnII, placed them in a new
      divergent group that is proposed to form a new Bradyrhizobium species,
      Bradyrhizobium algeriense sp. nov. (type strain RST89T, LMG 27618 and CECT 8363).
      Based on these phylogenetic markers and on genomic identity data derived from
      draft genomic sequences, Bradyrhizobium valentinum LmjM3T, Bradyrhizobium lablabi
      CCBAU 23086T, Bradyrhizobium retamae Ro19T, and Bradyrhizobium jicamae PAC68T are
      the closest relatives of B. algeriense RST89T, with sequence identities of 92-94%
      and Average Nucleotide Identities (ANIm) under 90%, well below the 95-96% species
      circumscription threshold. Likewise, a comparison of whole-cell proteomic
      patterns, estimated by Matrix-Assisted Laser Desorption/Ionization-Time-of-Flight
      (MALDI-TOF) mass spectrometric analysis, yielded almost identical spectra between
      B. algeriense strains but significant differences with B. valentinum,
      Bradyrhizobium paxllaeri, Bradyrhizobium icense, B. lablabi, B. jicamae and B.
      retamae. A phylogenetic tree based on symbiotic gene nodC revealed that the B.
      algeriense sequences cluster with sequences from the Bradyrhizobium symbiovar
      retamae, previously defined with B. retamae strains isolated from Retama
      monosperma. B. algeriense strains were able to establish effective symbioses with
      Retama raetam, Lupinus micranthus, Lupinus albus and Genista numidica, but not
      with Lupinus angustifolius or Glycine max.

PMID- 29656852
TI  - The New Standard: Personalised Information about the Risks and Benefits of
      Treatment Strategies for Localised Prostate Cancer.

PMID- 29656851
TI  - First-line Systemic Therapy for Metastatic Renal Cell Carcinoma: A Systematic
      Review and Network Meta-analysis.
AB  - CONTEXT: In the last decade, there has been a proliferation of treatment options
      for metastatic renal cell carcinoma (mRCC). However, direct comparative data are
      lacking for most of these agents. OBJECTIVE: To indirectly compare the efficacy
      and safety of systemic therapies used in the first-line treatment of mRCC.
      EVIDENCE ACQUISITION: Medline, EMBASE, Web of Science, and Scopus databases were
      searched using the OvidSP platform for studies indexed from database inception to
      October 23, 2017. Abstracts of conferences of relevant medical societies were
      included, and the systematic search was supplemented by hand search. For the
      systematic review, we identified any parallel-group randomized controlled trials
      assessing first-line systemic therapy. For network meta-analysis, we limited
      these to a clinically-relevant network based on standard practice patterns.
      Progression-free survival (PFS) was the primary outcome. Overall survival (OS)
      and grade 3 and 4 adverse events (AEs) were secondary outcomes. EVIDENCE
      SYNTHESIS: In total, 37 trials reporting on 13 128 patients were included in the
      systematic review. The network meta-analysis comprised 10 trials reporting on
      4819 patients. For PFS (10 trials, 4819 patients), there was a high likelihood
      (SUCRA 91%) that cabozantinib was the preferred treatment. For OS (5 trials, 3379
      patients), there was a 48% chance that nivolumab plus ipilimumab was the
      preferred option. There was a 67% likelihood that nivolumab plus ipilimumab was
      the best tolerated regime with respect to AEs. CONCLUSIONS: Cabozantinib and
      nivolumab plus ipilimumab are likely to be the preferred first-line agents for
      treating mRCC; however, direct comparative studies are warranted. These findings
      may provide guidance to patients and clinicians when making treatment decisions
      and may help inform future direct comparative trials. PATIENT SUMMARY: There are
      many treatment options for patients diagnosed with metastatic renal cell
      carcinoma. We indirectly compared the available options and found that
      cabozantinib and nivolumab plus ipilimumab are likely to be preferable choices as
      the first-line treatment in this situation.

PMID- 29656853
TI  - Re: Role of Genetic Testing for Inherited Prostate Cancer Risk: Philadelphia
      Prostate Cancer Consensus Conference 2017.

PMID- 29656854
TI  - Radical Prostatectomy in Metastatic Castration-resistant Prostate Cancer:
      Feasibility, Safety, and Quality of Life Outcomes.
AB  - : Ongoing prospective studies are evaluating treatment of the primary tumor in
      men with de novo metastatic prostate cancer (PCa). One potential benefit is
      prevention of morbidity from local progression. Thus, local therapy may be best
      applied selectively to men with local progression once resistance to first-line
      therapies has occurred. Here, we gather support for the hypothesis that radical
      prostatectomy (RP) is safe and preserves quality of life (QOL) when applied in
      men with metastatic castration-resistant PCa (mCRPC). We analyzed 14 patients who
      underwent RP in the setting of mCRPC from 2008 to 2016. Median time from mCRPC to
      RP was 5.1 mo (interquartile range [IQR] 1.4-12.0). Median preoperative and <3 mo
      postoperative Expanded Prostate Cancer Index Composite urinary function QOL
      scores were 84 (IQR 70-95) and 78 (IQR 62-81), respectively. There were one
      Clavien Grade III, three Grade II, and one Grade I complications postoperatively.
      In these patients with mCRPC, RP was feasible with limited minor complications.
      PATIENT SUMMARY: We report on a select group of men with metastatic castration
      resistant prostate cancer who had prostatectomy. Prostatectomy is highly
      investigational in this setting and should not be used outside of a clinical
      trial other than for symptom relief.

PMID- 29656855
TI  - Re: Jose Luis Perez-Gracia, Yohann Loriot, Jonathan E. Rosenberg, et al.
      Atezolizumab in Platinum-treated Locally Advanced or Metastatic Urothelial
      Carcinoma: Outcomes by Prior Number of Regimens. Eur Urol 2018;73:462-8.

PMID- 29656856
TI  - Reply to Francesco Massari and Vincenzo Di Nunno's Letter to the Editor re: Jose
      Luis Perez-Gracia, Yohann Loriot, Jonathan E. Rosenberg, et al. Atezolizumab in
      Platinum-treated Locally Advanced or Metastatic Urothelial Carcinoma: Outcomes by
      Prior Number of Regimens. Eur Urol 2018;73:462-8.

PMID- 29656857
TI  - Legacy Effect of Intensive Blood Glucose Control on Cardiovascular Outcomes in
      Patients With Type 2 Diabetes and Very High Risk or Secondary Prevention of
      Cardiovascular Disease: A Meta-analysis of Randomized Controlled Trials.
AB  - PURPOSE: We performed a meta-analysis to investigate the legacy effect of >5
      years of intensive blood glucose lowering on cardiovascular outcomes in patients
      with type 2 diabetes and very high risk or secondary prevention of cardiovascular
      disease (CVD). METHODS: We mainly searched PubMed, Embase, and the Cochrane
      Library for relevant randomized controlled trials. Patients in the included
      studies had intensive glucose lowering for >5 years and posttrial follow-up for
      at least 5 years. Primary end points were all-cause mortality and cardiovascular
      death. Secondary end points were major macrovascular events, myocardial
      infarction, and stroke. We used risk ratios (RRs) with 95% CIs as summary
      statistics. FINDINGS: We included 3 trials that involved 13,684 patients, of whom
      6805 received intensive glucose-lowering treatment and 6879 received standard
      treatment. The mean total follow-up duration was 10.3 years, which included 5.4
      years of in-trial intervention and 5.5 years of posttrial follow-up. Intensive
      glucose control treatment did not significantly reduce all-cause mortality (RR =
      0.98; 95% CI, 0.87-1.10) or cardiovascular death (RR = 0.97; 95% CI, 0.87-1.09).
      No significant risk reduction was found for stroke (RR = 1.02; 95% CI, 0.92
      1.14), myocardial infarction (RR = 0.91; 95% CI, 0.75-1.09), or major
      macrovascular events (RR = 0.99; 95% CI, 0.93-1.06). IMPLICATIONS: A legacy
      effect of >5-year intensive blood glucose control on cardiovascular outcomes in
      patients with type 2 diabetes and very high risk or secondary prevention of CVD
      was not detected, although this effect might be applicable in patients with
      diabetes and primary prevention of CVD. Further investigation of the legacy
      effect in different CVD risk populations should therefore be performed.

PMID- 29656858
TI  - A Recurrent De Novo PACS2 Heterozygous Missense Variant Causes Neonatal-Onset
      Developmental Epileptic Encephalopathy, Facial Dysmorphism, and Cerebellar
      Dysgenesis.
AB  - Developmental and epileptic encephalopathies (DEEs) represent a large clinical
      and genetic heterogeneous group of neurodevelopmental diseases. The
      identification of pathogenic genetic variants in DEEs remains crucial for
      deciphering this complex group and for accurately caring for affected individuals
      (clinical diagnosis, genetic counseling, impacting medical, precision therapy,
      clinical trials, etc.). Whole-exome sequencing and intensive data sharing
      identified a recurrent de novo PACS2 heterozygous missense variant in 14
      unrelated individuals. Their phenotype was characterized by epilepsy, global
      developmental delay with or without autism, common cerebellar dysgenesis, and
      facial dysmorphism. Mixed focal and generalized epilepsy occurred in the neonatal
      period, controlled with difficulty in the first year, but many improved in early
      childhood. PACS2 is an important PACS1 paralog and encodes a multifunctional
      sorting protein involved in nuclear gene expression and pathway traffic
      regulation. Both proteins harbor cargo(furin)-binding regions (FBRs) that bind
      cargo proteins, sorting adaptors, and cellular kinase. Compared to the defined
      PACS1 recurrent variant series, individuals with PACS2 variant have more
      consistently neonatal/early-infantile-onset epilepsy that can be challenging to
      control. Cerebellar abnormalities may be similar but PACS2 individuals exhibit a
      pattern of clear dysgenesis ranging from mild to severe. Functional studies
      demonstrated that the PACS2 recurrent variant reduces the ability of the
      predicted autoregulatory domain to modulate the interaction between the PACS2 FBR
      and client proteins, which may disturb cellular function. These findings support
      the causality of this recurrent de novo PACS2 heterozygous missense in DEEs with
      facial dysmorphim and cerebellar dysgenesis.

PMID- 29656861
TI  - Efficacy of Growth Hormone Treatment in Children with Type 1 Diabetes Mellitus
      and Growth Hormone Deficiency-An Analysis of KIGS Data.
AB  - OBJECTIVE: To analyze first-year treatment growth response and growth hormone
      (GH) dosage in prepubertal patients with the combination of type 1 diabetes
      mellitus (T1DM) and growth hormone deficiency (GHD). STUDY DESIGN: A total of 69
      patients with T1DM and GHD treated with GH have been enrolled in KIGS (Pfizer
      International Growth Database). Of these, 24 prepubertal patients had developed
      T1DM before GHD and were included in this analysis. Of 30 570 patients with GHD
      without T1DM, 15 024 were prepubertal and served as controls. Values are
      expressed as mean +/- SD. RESULTS: Patients with T1DM and GHD had similar
      characteristics compared with the GHD-alone group. Neither age (10.2 +/- 3.13 vs
      8.42 +/- 3.46 years, P = .14), height SDS corrected for midparental height SDS at
      start of treatment (-1.62 +/- 1.38 vs -1.61 +/- 1.51, P = .80), nor GH dosage
      (0.24 +/- 0.08 mg/kg/wk vs 0.20 +/- 0.04 mg/kg/wk, P = .09) were different
      between those with and without T1DM. First-year catch-up growth was comparable
      between the 2 patient groups (first treatment year height velocity 7.54 +/- 3.11
      cm/year compared with 8.35 +/- 2.54 cm/year in control patients, P = .38). Height
      SDS of children with T1DM and GHD improved from -2.62 +/- 1.04 to -1.88 +/- 1.11
      over 1 year of GH treatment. CONCLUSION: Short-term response to GH therapy
      appeared similar in subjects with T1DM who then developed GHD and in those with
      GHD alone. Thus, T1DM does not appear to compromise GH response in children with
      GHD and should not exclude GH treatment in these children. GH treatment was safe
      in both subgroups of patients.

PMID- 29656859
TI  - Dual Molecular Effects of Dominant RORA Mutations Cause Two Variants of Syndromic
      Intellectual Disability with Either Autism or Cerebellar Ataxia.
AB  - RORalpha, the RAR-related orphan nuclear receptor alpha, is essential for
      cerebellar development. The spontaneous mutant mouse staggerer, with an ataxic
      gait caused by neurodegeneration of cerebellar Purkinje cells, was discovered two
      decades ago to result from homozygous intragenic Rora deletions. However, RORA
      mutations were hitherto undocumented in humans. Through a multi-centric
      collaboration, we identified three copy-number variant deletions (two de novo and
      one dominantly inherited in three generations), one de novo disrupting
      duplication, and nine de novo point mutations (three truncating, one canonical
      splice site, and five missense mutations) involving RORA in 16 individuals from
      13 families with variable neurodevelopmental delay and intellectual disability
      (ID)-associated autistic features, cerebellar ataxia, and epilepsy. Consistent
      with the human and mouse data, disruption of the D. rerio ortholog, roraa, causes
      significant reduction in the size of the developing cerebellum. Systematic in
      vivo complementation studies showed that, whereas wild-type human RORA mRNA could
      complement the cerebellar pathology, missense variants had two distinct
      pathogenic mechanisms of either haploinsufficiency or a dominant toxic effect
      according to their localization in the ligand-binding or DNA-binding domains,
      respectively. This dichotomous direction of effect is likely relevant to the
      phenotype in humans: individuals with loss-of-function variants leading to
      haploinsufficiency show ID with autistic features, while individuals with de novo
      dominant toxic variants present with ID, ataxia, and cerebellar atrophy. Our
      combined genetic and functional data highlight the complex mutational landscape
      at the human RORA locus and suggest that dual mutational effects likely determine
      phenotypic outcome.

PMID- 29656862
TI  - "Toxicohistrionics": Flint, Michigan and the Lead Crisis.

PMID- 29656863
TI  - Prevalence of Functional Defecation Disorders in Children: A Systematic Review
      and Meta-Analysis.
AB  - OBJECTIVE: To systematically review the literature regarding the epidemiology of
      functional constipation and functional nonretentive fecal incontinence (FNRFI) in
      children. Secondary objectives were to assess the geographical, age, and sex
      distribution of functional constipation and FNRFI and to evaluate associated
      factors. STUDY DESIGN: The Cochrane Library, PubMed, and Embase databases were
      searched from 2006 until September 2017. The following inclusion criteria were
      applied: (1) prospective studies of population-based samples; (2) reporting on
      the prevalence of functional constipation or FNRFI according to the Rome III/IV
      criteria; (3) in children aged 0-18 years; and (4) published in full manuscript
      form. A quality assessment of included studies was conducted. Random effect meta
      analyses with meta-regression analyses of study characteristics were performed.
      RESULTS: Thirty-seven studies were included, of which 35 reported on the
      prevalence of functional constipation and 15 of FNRFI. The reported prevalence of
      functional constipation ranged from 0.5% to 32.2%, with a pooled prevalence of
      9.5% (95% CI 7.5-12.1). The prevalence of FRNFI ranged from 0.0% to 1.8%, with a
      pooled prevalence of 0.4% (95% CI 0.2-0.7). The prevalence of functional
      constipation was 8.6% in boys compared with 8.9% in girls (OR 0.99, 95% CI 0.9
      1.4). Geographical location, dietary habits, and exposure to stressful life
      events were reported to be associated with the prevalence of functional
      constipation. Data on FNRFI were scarce and no associated factors were
      identified. CONCLUSION: Functional constipation is common in childhood and is
      associated with geographical location, lifestyle factors, and stressful life
      events. FNRFI is rare, and no associated factors were identified.

PMID- 29656864
TI  - Long-Term Outcome of Sacrococcygeal Teratoma: A Controlled Cohort Study of
      Urinary Tract and Bowel Dysfunction and Predictors of Poor Outcome.
AB  - OBJECTIVE: To evaluate urinary tract and bowel function in children with
      sacrococcygeal teratoma, compare the findings with healthy children, and assess
      predictors of poor outcome. STUDY DESIGN: This was a controlled cohort study of
      all patients operated for sacrococcygeal teratoma at a tertiary pediatric surgery
      center, 2000-2013. Urinary and bowel function were compared with healthy control
      patients matched for age and sex. Perioperative and histopathologic risk factors
      were analyzed. RESULTS: In total, 17 patients with sacrococcygeal teratoma and 85
      healthy control patients were included in the study. Patients with sacrococcygeal
      teratoma more often were reported to have uncontrolled voiding (12% vs 0%, P <
      .01), difficulty in bladder emptying (24% vs 0%, P < .001), and pyelonephritis
      (18% vs 1%, P < .05). Constipation was more common in patients with
      sacrococcygeal teratoma (47 % vs 14%, P < .05), but the overall bowel function
      score was equal in the 2 groups. Children with large tumors and immature
      histology were more likely to have a dysfunctional outcome (P < .05).
      CONCLUSIONS: Uncontrolled voiding, difficulty in bladder emptying,
      pyelonephritis, and constipation were more common in patients with sacrococcygeal
      teratoma than in healthy children. Dysfunctional outcome was more prevalent in
      children with large and immature teratomas.

PMID- 29656865
TI  - When and How Do Brief Alcohol Interventions in Primary Care Reduce Alcohol Use
      and Alcohol-Related Consequences among Adolescents?
AB  - OBJECTIVE: To systematically describe when and how brief alcohol interventions
      delivered to adolescents in primary care settings reduce alcohol use and alcohol
      related consequences among adolescents, using realist review methodology. STUDY
      DESIGN: Eleven electronic databases, gray literature, and reference screening
      were searched up to June 2016; 11 brief interventions published in 13 studies met
      inclusion criteria. Intervention design components (delivery context and
      intervention mechanisms) underlying brief alcohol interventions for adolescents
      were extracted and linked to alcohol use and related consequences. RESULTS: Brief
      interventions had either an indicated context of delivery (provided to adolescent
      patients with low-to-moderate risk for alcohol problems) or universal context of
      delivery (provided to general adolescent patient population). Interventions that
      used motivational interviewing in an indicated delivery context had 2 potential
      mechanisms-eliciting and strengthening motivation to change and providing
      direction through interpretation. These interventions resulted in clinically
      significant reductions in alcohol use and associated consequences. Peer risk also
      was identified among universal and indicated brief interventions as a potential
      mechanism for changing alcohol-related outcomes among adolescents who received
      the intervention. None of the studies tested the processes by which interventions
      were expected to work. CONCLUSIONS: The current evidence base suggests that both
      indicated and universal delivery of brief alcohol interventions to adolescents in
      primary care settings can result in clinically important changes in alcohol
      related outcomes. Studies that test brief intervention processes are now
      necessary to better understand how brief interventions work with adolescents in
      primary care settings.

PMID- 29656860
TI  - Truncating Variants in NAA15 Are Associated with Variable Levels of Intellectual
      Disability, Autism Spectrum Disorder, and Congenital Anomalies.
AB  - N-alpha-acetylation is a common co-translational protein modification that is
      essential for normal cell function in humans. We previously identified the
      genetic basis of an X-linked infantile lethal Mendelian disorder involving a
      c.109T>C (p.Ser37Pro) missense variant in NAA10, which encodes the catalytic
      subunit of the N-terminal acetyltransferase A (NatA) complex. The auxiliary
      subunit of the NatA complex, NAA15, is the dimeric binding partner for NAA10.
      Through a genotype-first approach with whole-exome or genome sequencing (WES/WGS)
      and targeted sequencing analysis, we identified and phenotypically characterized
      38 individuals from 33 unrelated families with 25 different de novo or inherited,
      dominantly acting likely gene disrupting (LGD) variants in NAA15. Clinical
      features of affected individuals with LGD variants in NAA15 include variable
      levels of intellectual disability, delayed speech and motor milestones, and
      autism spectrum disorder. Additionally, mild craniofacial dysmorphology,
      congenital cardiac anomalies, and seizures are present in some subjects. RNA
      analysis in cell lines from two individuals showed degradation of the transcripts
      with LGD variants, probably as a result of nonsense-mediated decay. Functional
      assays in yeast confirmed a deleterious effect for two of the LGD variants in
      NAA15. Further supporting a mechanism of haploinsufficiency, individuals with
      copy-number variant (CNV) deletions involving NAA15 and surrounding genes can
      present with mild intellectual disability, mild dysmorphic features, motor
      delays, and decreased growth. We propose that defects in NatA-mediated N-terminal
      acetylation (NTA) lead to variable levels of neurodevelopmental disorders in
      humans, supporting the importance of the NatA complex in normal human
      development.

PMID- 29656866
TI  - Corrigendum to "An association study of established breast cancer reproductive
      and lifestyle risk factors with tumour subtype defined by the prognostic 70-gene
      expression signature (MammaPrint(r))" [Eur J Cancer 75 (April 2017) 5-13].

PMID- 29656867
TI  - Surgical treatment of metachronous rectal liver and lung metastases: A combined
      videolaparoscopic and videothoracoscopic approach.

PMID- 29656868
TI  - Dynamics of EGFR Mutation Load in Plasma for Prediction of Treatment Response and
      Disease Progression in Patients With EGFR-Mutant Lung Adenocarcinoma.
AB  - BACKGROUND: The assessment of epidermal growth factor receptor (EGFR) mutations
      is crucial for the management of patients with lung adenocarcinoma. Circulating
      tumor DNA (ctDNA)-based assessment offers advantages over tumor as a minimally
      invasive method able to capture tumor heterogeneity. PATIENTS AND METHODS:
      Consecutive patients diagnosed with EGFR-mutant lung adenocarcinoma in tumor
      biopsy were included in this study. Plasma samples were obtained at different
      time points during the course of the disease. EGFR mutations in plasma were
      quantified using BEAMing (beads, emulsions, amplification, and magnetics) or
      digital PCR and were correlated with mutations in tumor and with radiologic
      response and progression. RESULTS: Two hundred twenty-one plasma samples from 33
      patients were analyzed. EGFR mutations in plasma were detected in 83% of all
      patients and 100% of those with extrathoracic metastases. The dynamics of the
      EGFR mutation load predicted response in 93% and progression in 89% of cases well
      in advance of radiologic evaluation. Progression-free survival for patients in
      whom ctDNA was not detected in plasma during treatment was significantly longer
      than for those in whom ctDNA remained detectable (295 vs. 55 days; hazard ratio,
      17.1; P < .001). CONCLUSION: The detection of EGFR mutations in ctDNA showed good
      correlation with that in tumor biopsy and predicted tumor response and
      progression in most patients. The liquid biopsy for ctDNA-based assessment of
      EGFR mutations is a reliable technique for diagnosis and follow-up in patients
      with EGFR-mutant lung adenocarcinoma in routine clinical practice.

PMID- 29656869
TI  - Comparing Treatment Strategies for Stage I Small-cell lung Cancer.
AB  - INTRODUCTION: The diagnosis of stage I small-cell lung cancer (SCLC) is
      increasing in incidence with the advent of low-dose screening computed
      tomography. Surgery is considered the standard of care but there are very few
      data to guide clinical decision-making. The purpose of this study was to compare
      outcomes for patients receiving definitive surgery, stereotactic body radiation
      therapy (SBRT), or external beam radiation therapy (EBRT) for stage I SCLC.
      PATIENTS AND METHODS: Patients with a primary diagnosis of stage I SCLC were
      identified in the National Cancer Database. Patients were defined as having a
      first course of treatment of either surgery, EBRT, or SBRT. Overall survival (OS)
      was determined using the Kaplan-Meier method and Cox proportional hazards
      regression methods were used to estimate risk of overall mortality. RESULTS: A
      total of 2678 patients were included in the analysis. The 2- and 3-year OS for
      the whole cohort was 62% and 50%. Comparing treatment strategies in a
      multivariate model, surgical resection showed improved OS over EBRT (P < .001)
      and SBRT (P < .001), however, the OS benefit over SBRT did not persist for
      patients who underwent limited resection. When excluding patients who underwent
      surgery, SBRT showed improved OS compared with EBRT (P = .04). Additional use of
      chemotherapy with any treatment modality resulted in improved OS (P < .001).
      CONCLUSION: In this hospital-based registry study, definitive surgical resection
      and use of chemotherapy resulted in improved survival for patients with early
      stage SCLC. For patients who are not candidates for surgery, SBRT may offer a
      survival benefit compared with standard EBRT.

PMID- 29656870
TI  - Distinct Accumbens Shell Output Pathways Promote versus Prevent Relapse to
      Alcohol Seeking.
AB  - Contexts exert bi-directional control over relapse to drug seeking. Contexts
      associated with drug self-administration promote relapse, whereas contexts
      associated with the absence of self-administration protect against relapse. The
      nucleus accumbens shell (AcbSh) is a key brain region determining these roles of
      context. However, the specific cell types, and projections, by which AcbSh serves
      these dual roles are unknown. Here, we show that contextual control over relapse
      and abstinence is embedded within distinct output circuits of dopamine 1 receptor
      (Drd1) expressing AcbSh neurons. We report anatomical and functional segregation
      of Drd1 AcbSh output pathways during context-induced reinstatement and extinction
      of alcohol seeking. The AcbSh->ventral tegmental area (VTA) pathway promotes
      relapse via projections to VTA Gad1 neurons. The AcbSh->lateral hypothalamus (LH)
      pathway promotes extinction via projections to LH Gad1 neurons. Targeting these
      opposing AcbSh circuit contributions may reduce propensity to relapse to, and
      promote abstinence from, drug use.

PMID- 29656871
TI  - Activation of Galphaq Signaling Enhances Memory Consolidation and Slows Cognitive
      Decline.
AB  - Perhaps the most devastating decline with age is the loss of memory. Therefore,
      identifying mechanisms to restore memory function with age is critical. Using C.
      elegans associative learning and memory assays, we identified a gain-of-function
      Galphaq signaling pathway mutant that forms a long-term (cAMP response element
      binding protein [CREB]-dependent) memory following one conditioned stimulus
      unconditioned stimulus (CS-US) pairing, which usually requires seven CS-US
      pairings. Increased CREB activity in AIM interneurons reduces the threshold for
      memory consolidation through transcription of a set of previously identified
      "long-term memory" genes. Enhanced Galphaq signaling in the AWC sensory neuron is
      both necessary and sufficient for improved memory and increased AIM CREB
      activity, and activation of Galphaq specifically in aged animals rescues the
      ability to form memory. Activation of Galphaq in AWC sensory neurons non-cell
      autonomously induces consolidation after one CS-US pairing, enabling both
      cognitive function maintenance with age and restoration of memory function in
      animals with impaired memory performance without decreased longevity.

PMID- 29656872
TI  - The Medial Prefrontal Cortex Shapes Dopamine Reward Prediction Errors under State
      Uncertainty.
AB  - Animals make predictions based on currently available information. In natural
      settings, sensory cues may not reveal complete information, requiring the animal
      to infer the "hidden state" of the environment. The brain structures important in
      hidden state inference remain unknown. A previous study showed that midbrain
      dopamine neurons exhibit distinct response patterns depending on whether reward
      is delivered in 100% (task 1) or 90% of trials (task 2) in a classical
      conditioning task. Here we found that inactivation of the medial prefrontal
      cortex (mPFC) affected dopaminergic signaling in task 2, in which the hidden
      state must be inferred ("will reward come or not?"), but not in task 1, where the
      state was known with certainty. Computational modeling suggests that the effects
      of inactivation are best explained by a circuit in which the mPFC conveys
      inference over hidden states to the dopamine system. VIDEO ABSTRACT.

PMID- 29656873
TI  - Vision and Locomotion Shape the Interactions between Neuron Types in Mouse Visual
      Cortex.
AB  - Cortical computation arises from the interaction of multiple neuronal types,
      including pyramidal (Pyr) cells and interneurons expressing Sst, Vip, or Pvalb.
      To study the circuit underlying such interactions, we imaged these four types of
      cells in mouse primary visual cortex (V1). Our recordings in darkness were
      consistent with a "disinhibitory" model in which locomotion activates Vip cells,
      thus inhibiting Sst cells and disinhibiting Pyr cells. However, the disinhibitory
      model failed when visual stimuli were present: locomotion increased Sst cell
      responses to large stimuli and Vip cell responses to small stimuli. A recurrent
      network model successfully predicted each cell type's activity from the measured
      activity of other types. Capturing the effects of locomotion, however, required
      allowing it to increase feedforward synaptic weights and modulate recurrent
      weights. This network model summarizes interneuron interactions and suggests that
      locomotion may alter cortical computation by changing effective synaptic
      connectivity.

PMID- 29656874
TI  - Regional Heterogeneity of D2-Receptor Signaling in the Dorsal Striatum and
      Nucleus Accumbens.
AB  - Dopamine input to the dorsal and ventral striatum originates from separate
      populations of midbrain neurons. Despite differences in afferent inputs and
      behavioral output, little is known about how dopamine release is encoded by
      dopamine receptors on medium spiny neurons (MSNs) across striatal subregions.
      Here we examined the activation of D2 receptors following the synaptic release of
      dopamine in the dorsal striatum (DStr) and nucleus accumbens (NAc) shell. We
      found that D2 receptor-mediated synaptic currents were slower in the NAc and this
      difference occurred at the level of D2-receptor signaling. As a result of
      preferential coupling to Galphao, we also found that D2 receptors in MSNs
      demonstrated higher sensitivity for dopamine in the NAc. The higher sensitivity
      in the NAc was eliminated following cocaine exposure. These results identify
      differences in the sensitivity and timing of D2-receptor signaling across the
      striatum that influence how nigrostriatal and mesolimbic signals are encoded
      across these circuits.

PMID- 29656875
TI  - Structural Mechanism of Functional Modulation by Gene Splicing in NMDA Receptors.
AB  - Alternative gene splicing gives rise to N-methyl-D-aspartate (NMDA) receptor ion
      channels with defined functional properties and unique contributions to calcium
      signaling in a given chemical environment in the mammalian brain. Splice variants
      possessing the exon-5-encoded motif at the amino-terminal domain (ATD) of the
      GluN1 subunit are known to display robustly altered deactivation rates and pH
      sensitivity, but the underlying mechanism for this functional modification is
      largely unknown. Here, we show through cryoelectron microscopy (cryo-EM) that the
      presence of the exon 5 motif in GluN1 alters the local architecture of
      heterotetrameric GluN1-GluN2 NMDA receptors and creates contacts with the ligand
      binding domains (LBDs) of the GluN1 and GluN2 subunits, which are absent in NMDA
      receptors lacking the exon 5 motif. The unique interactions established by the
      exon 5 motif are essential to the stability of the ATD/LBD and LBD/LBD interfaces
      that are critically involved in controlling proton sensitivity and deactivation.

PMID- 29656876
TI  - Alternative 3' UTRs Modify the Localization, Regulatory Potential, Stability, and
      Plasticity of mRNAs in Neuronal Compartments.
AB  - Neurons localize mRNAs near synapses where their translation can be regulated by
      synaptic demand and activity. Differences in the 3' UTRs of mRNAs can change
      their localization, stability, and translational regulation. Using 3' end RNA
      sequencing of microdissected rat brain slices, we discovered a huge diversity in
      mRNA 3' UTRs, with many transcripts showing enrichment for a particular 3' UTR
      isoform in either somata or the neuropil. The 3' UTR isoforms of localized
      transcripts are significantly longer than the 3' UTRs of non-localized
      transcripts and often code for proteins associated with axons, dendrites, and
      synapses. Surprisingly, long 3' UTRs add not only new, but also duplicate
      regulatory elements. The neuropil-enriched 3' UTR isoforms have significantly
      longer half-lives than somata-enriched isoforms. Finally, the 3' UTR isoforms can
      be significantly altered by enhanced activity. Most of the 3' UTR plasticity is
      transcription dependent, but intriguing examples of changes that are consistent
      with altered stability, trafficking between compartments, or local "remodeling"
      remain.

PMID- 29656877
TI  - Corrigendum to "ERK1/2/mTOR/Stat3 pathway-mediated autophagy alleviates traumatic
      brain injury-induced acute lung injury" [Biochim. Biophys. Acta 1864/5PA(2018)
      1663-1674].

PMID- 29656878
TI  - Postoperative headache following treatment of vestibular schwannoma: A literature
      review.
AB  - Vestibular schwannoma (VS) is a brain tumour arising from Schwann cells that is
      typically closely associated with the vestibulocochlear nerve. Post-operative
      headaches (POH) are a potentially common complication of surgery for VS. Greatly
      differing rates of POH have previously been reported, particularly with different
      surgical approaches. The aim of this review is to identify and summarise the
      available peer-reviewed evidence on rates of POH following operative (or
      radiosurgery) treatment for VS, in addition to information about the treatment
      and prognosis of POH in these patients. A systematic search was conducted of
      Pubmed, Medline, Scopus and EMBASE in April 2017 using the medical subject
      headings (acoustic neuroma OR vestibular schwannoma) AND headache. Eligibility
      determination and data extraction were performed in duplicate with standardised
      forms. POH is common following surgery for VS. Differing rates of POH have been
      reported with different management approaches, patient age and tumour size. There
      are relatively few studies that have directly compared the rates of POH with
      different surgical approaches. The retrosigmoid approach with craniotomy appears
      to have lower rates of POH than when the retrosigmoid approach is performed with
      craniectomy. Patients under the age of 65 and with tumours <1.5 cm in size appear
      to have a higher risk of POH. The most commonly documented management of POH
      involves simple analgesia, although the majority of patients report this
      treatment is of only minimal benefit. Further prospective studies comparing rates
      of POH following different surgical approaches and radiosurgery are required.

PMID- 29656879
TI  - Analysis of changes in cervical spinal curvature and intervertebral disk space
      height following ACDF surgery in a group of 100 patients followed up for 12
      months.
AB  - We analysed 100 patients following anterior cervical discectomy and fusion with
      interbody stabilisation with PEEK cages. Radiographs obtained preoperatively and
      during the 12-month follow-up were compared to track changes in overall and local
      cervical lordosis and disk space height. Subsidence was defined as cage migration
      >= 3 mm into the adjacent endplates. Mean change in operated disk space height
      was 1.13 +/- 1.33 mm. Subsidence was detected in 10.23% of the operated spaces.
      Mean change in overall cervical lordosis was 1.31 +/- 5.71 degrees, and mean
      change in local lordosis was 0.19 +/- 4.71 degrees. Change in overall cervical
      lordosis correlated with change in local lordosis (r = 0.61, p < 0.01). The
      greatest changes in lordosis and disk space height were noted immediately post
      surgery. Baseline values were approximated gradually over time, but the post
      operative values at 12 months were still higher than baseline. Disk space height
      change did not correlate with changes in patient-reported pain intensity at
      baseline (VAS 0) vs. at 12 months post-operatively (VAS 12) (r = 0.12, p < 0.05)
      or changes in the Neck Disability Index (NDI) at baseline (NDI 0) vs. at 12
      months post-operatively (NDI 12) (r = -0.02, p = 0.05). Changes in overall
      cervical lordosis did not directly influence treatment outcomes assessed by
      comparing VAS 0 vs. VAS 12 (r = 0.13, p = 0.24) or NDI 0 vs. NDI 12 (r = -0.0005,
      p = 0.96). Surgical outcomes depend primarily on adequate decompression of the
      spinal cord and nerve roots. Post-operative radiological changes did not directly
      influence patients' pain level or quality of life.

PMID- 29656880
TI  - Fundamentals of functional imaging II: emerging MR techniques and new methods of
      analysis.
AB  - Current multiparameter MRI protocols integrate structural, physiological, and
      metabolic information about cancer. Emerging techniques such as arterial spin
      labeling (ASL), blood oxygen level dependent (BOLD), MR elastography, chemical
      exchange saturation transfer (CEST), and hyperpolarization provide new
      information and will likely be integrated into daily clinical practice in the
      near future. Furthermore, there is great interest in the study of tumor
      heterogeneity as a prognostic factor and in relation to resistance to treatment,
      and this interest is leading to the application of new methods of analysis of
      multiparametric protocols. In parallel, new oncologic biomarkers that integrate
      the information from MR with clinical, laboratory, genetic, and histologic
      findings are being developed, thanks to the application of big data and
      artificial intelligence. This review analyzes different emerging MR techniques
      that are able to evaluate the physiological, metabolic, and mechanical
      characteristics of cancer, as well as the main clinical applications of these
      techniques. In addition, it summarizes the most novel methods of analysis of
      functional radiologic information in oncology.

PMID- 29656881
TI  - Fundamentals of functional imaging I: current clinical techniques.
AB  - Imaging techniques can establish a structural, physiological, and molecular
      phenotype for cancer, which helps enable accurate diagnosis and personalized
      treatment. In recent years, various imaging techniques that make it possible to
      study the functional characteristics of tumors quantitatively and reproducibly
      have been introduced and have become established in routine clinical practice.
      Perfusion studies enable us to estimate the microcirculation as well as tumor
      angiogenesis and permeability using ultrafast dynamic acquisitions with
      ultrasound, computed tomography, or magnetic resonance (MR) imaging. Diffusion
      weighted sequences now form part of state-of-the-art MR imaging protocols to
      evaluate oncologic lesions in any anatomic location. Diffusion-weighted imaging
      provides information about the occupation of the extracellular and extravascular
      space and indirectly estimates the cellularity and apoptosis of tumors, having
      demonstrated its relation with biologic aggressiveness in various tumor lines and
      its usefulness in the evaluation of the early response to systemic and local
      targeted therapies. Another tool is hydrogen proton MR spectroscopy, which is
      used mainly in the study of the metabolic characteristics of brain tumors.
      However, the complexity of the technique and its lack of reproducibility have
      limited its clinical use in other anatomic areas, although much experience with
      the use of this technique in the assessment of prostate and breast cancers as
      well as liver lesions has also accumulated. This review analyzes the imaging
      techniques that make it possible to evaluate the physiological and molecular
      characteristics of cancer that have already been introduced into clinical
      practice, such as techniques that evaluate angiogenesis through dynamic
      acquisitions after the administration of contrast material, diffusion-weighted
      imaging, or hydrogen proton MR spectroscopy, as well as their principal
      applications in oncology.

PMID- 29656882
TI  - Factors Influencing Choice of Radiology and Relationship to Resident Job
      Satisfaction.
AB  - PURPOSE: Identify when current radiology residents initially became interested in
      radiology, which factors influenced their decision to pursue a career in
      radiology, and which factors correlate with job satisfaction. METHODS: An online
      survey was distributed to United States radiology residents between December 7,
      2016 and March 31, 2017. Respondents identified the most appealing aspects of
      radiology during medical school, identified experiences most influential in
      choosing radiology, and scored job satisfaction on visual analog scales. Relative
      importance was compared with descriptive statistics. Satisfaction scores were
      compared across factors with analysis of variance and post-hoc Tukey tests.
      RESULTS: 488 radiology residents responded (age 30.8 +/- 3.2 years; 358 male, 129
      female, 1 unknown; 144 PGY2, 123 PGY3, 103 PGY4, 118 PGY5). The most influential
      aspects in choosing radiology were the intellectual (n=187, 38%), imaging (n=100,
      20%), and procedural (n=96, 20%) components and potential lifestyle (n=69, 14%).
      Radiology clerkship reading room shadowing (n=143, 29%), radiologist mentor
      (n=98, 20%), non-radiology clerkship imaging exposure (n=77, 16%), and radiology
      clerkship interventions exposure (n=75, 15%) were most influential. Choosing
      radiology because of potential lifestyle correlated with less job satisfaction
      than choosing radiology for intellectual (p=0.0004) and imaging (p=0.0003)
      components. CONCLUSION: Recruitment of medical students into radiology may be
      most effective when radiology clerkships emphasize the intellectual and imaging
      components of radiology through reading room shadowing and exposure to
      interventions. Choosing radiology for lifestyle correlates with less job
      satisfaction, at least during residency.

PMID- 29656883
TI  - Variability in the Use of Simulation for Procedural Training in Radiology
      Residency: Opportunities for Improvement.
AB  - OBJECTIVE: Increased attention to quality and safety has led to a re-evaluation
      of the classic apprenticeship model for procedural training. Many have proposed
      simulation as a supplementary teaching tool. The purpose of this study was to
      assess radiology resident exposure to procedural training and procedural
      simulation. MATERIALS AND METHODS: An IRB-exempt online survey was distributed to
      current radiology residents in the United States by e-mail. Survey results were
      summarized using frequency and percentages. Chi-square tests were used for
      statistical analysis where appropriate. RESULTS: A total of 353 current residents
      completed the survey. 37% (n = 129/353) of respondents had never used procedure
      simulation. Of the residents who had used simulation, most did not do so until
      after having already performed procedures on patients (59%, n = 132/223). The
      presence of a dedicated simulation center was reported by over half of residents
      (56%, n = 196/353) and was associated with prior simulation experience (P =
      0.007). Residents who had not had procedural simulation were somewhat likely or
      highly likely (3 and 4 on a 4-point Likert-scale) to participate if it were
      available (81%, n = 104/129). Simulation training was associated with higher
      comfort levels in performing procedures (P < 0.001). CONCLUSIONS: Although
      procedural simulation training is associated with higher comfort levels when
      performing procedures, there is variable use in radiology resident training and
      its use is not currently optimized. Given the increased emphasis on patient
      safety, these results suggest the need to increase procedural simulation use
      during residency, including an earlier introduction to simulation before patient
      exposure.

PMID- 29656884
TI  - Editorial Comment.

PMID- 29656885
TI  - Editorial Comment.

PMID- 29656886
TI  - Oscillatory squeeze film analysis of soft contact lenses.
AB  - The complex modulus of a soft contact lens affects the optical performance,
      fitting, on-eye movement, wettability, physiological impact and overall comfort
      of the lens. However, despite acknowledgement that the mechanical behaviour of
      contact lenses is time-dependent, the rheological characteristics of contact
      lenses remain under-defined. While existing studies have focussed on elasticity
      to describe lens behaviour, this paper proposes using oscillatory squeeze film
      analysis to evaluate the complex modulus. The effects of excitation amplitude,
      repeatability and surface wetness are examined for four commercially available
      lenses. Slip at the lens/platen interface is considered along with bias
      introduced by pre-compressing the lens between platens. Test results when
      compared to results reported from other test methods indicate that a high degree
      of slip occurs at the lens platen interface suggesting that deformation is
      primarily due to biaxial extension.

PMID- 29656887
TI  - Sarcopenia and adiposity linked to overall survival.

PMID- 29656888
TI  - Animal models of acute otitis media - A review with practical implications for
      laboratory research.
AB  - Considerable animal research has focused on developing new strategies for the
      prevention and treatment of acute otitis media (AOM). Several experimental models
      of AOM have thus been developed. A PubMed search of the English literature was
      conducted from 1975 to July 2016 using the search terms "animal model" and
      "otitis media" from which 91 published studies were included for analysis,
      yielding 123 animal models. The rat, mouse and chinchilla are the preferred
      animals for experimental AOM models with their individual advantages and
      disadvantages. The most common pathogens used to create AOM are Streptococcus
      pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. Streptococcus
      pneumoniae (types 3, 23 and 6A) and non-typeable Haemophilus influenzae (NTHi)
      are best options for inoculation into rat and mouse models. Adding viral
      pathogens such as RSV and Influenza A virus, along with creating ET dysfunction,
      are useful adjuncts in animal models of AOM. Antibiotic prophylaxis may interfere
      with the inflammatory response without a significant reduction in animal
      mortality.

PMID- 29656889
TI  - 3-D treatment planning system-Leksell Gamma Knife treatment planning system.
AB  - Leksell Gamma Plan (LGP), the treatment planning system for the Leksell Gamma
      Knife (LGK) stereotactic radiosurgery, has evolved from the primitive KULA system
      to the present-day powerful version of image-guided stereotactic radiosurgery.
      Through many years of development, LGP has improved on its dose calculation
      accuracy, speed, and user interface. This allows more accurate irradiation of the
      target while sparing the nearby normal tissues and critical structures better.

PMID- 29656890
TI  - Indolyl-isoxazolidines attenuate LPS-stimulated pro-inflammatory cytokines and
      increase survival in a mouse model of sepsis: Identification of potent lead.
AB  - A library of indolyl-isoxazolidines (6-9) has been synthesized by regio- and
      stereoselective microwave irradiated 1,3-dipolar cycloadditions of C-(3-indolyl)
      N-phenylnitrone (2') with variedly substituted dipolarophiles (3'-5') and
      screened for their anti-inflammatory activities through inhibition of pro
      inflammatory cytokines such as TNF-alpha and IL-6. Amongst the evaluated
      compounds (6-9), bicyclic isoxazolidine (9a) was found to exhibit significant
      inhibitory potential against LPS induced human IL-6 and TNF-alpha in THP-1 cells.
      Compound 9a was further assessed for in vivo analgesic and anti-inflammatory
      activities via acetic acid induced writhing and carrageenan induced paw edema
      models in mice, respectively. The results showed that compound possesses potent
      anti-inflammatory-analgesic activity comparable to indomethacin and did not show
      toxicity up to a 2000 mg kg-1 dose as evidenced by histopathological studies.
      Consequently, the most active compound 9a was also evaluated against LPS-induced
      septic death and exhibited a significant protection in in vivo mouse model. Taken
      all together, the results suggest that the compound 9a is able to attenuate pro
      inflammatory cytokines such as IL-6 and TNF-alpha; accelerate resolution of
      inflammation, and also increased survival rate of septic mice. Therefore, these
      "lead" isoxazolidines can be used as promising candidate for further
      analgesic/anti-inflammatory drug design and development.

PMID- 29656892
TI  - Cancer-Germline Antigen Expression Discriminates Clinical Outcome to CTLA-4
      Blockade.
AB  - CTLA-4 immune checkpoint blockade is clinically effective in a subset of patients
      with metastatic melanoma. We identify a subcluster of MAGE-A cancer-germline
      antigens, located within a narrow 75 kb region of chromosome Xq28, that predicts
      resistance uniquely to blockade of CTLA-4, but not PD-1. We validate this gene
      expression signature in an independent anti-CTLA-4-treated cohort and show its
      specificity to the CTLA-4 pathway with two independent anti-PD-1-treated cohorts.
      Autophagy, a process critical for optimal anti-cancer immunity, has previously
      been shown to be suppressed by the MAGE-TRIM28 ubiquitin ligase in vitro. We now
      show that the expression of the key autophagosome component LC3B and other
      activators of autophagy are negatively associated with MAGE-A protein levels in
      human melanomas, including samples from patients with resistance to CTLA-4
      blockade. Our findings implicate autophagy suppression in resistance to CTLA-4
      blockade in melanoma, suggesting exploitation of autophagy induction for
      potential therapeutic synergy with CTLA-4 inhibitors.

PMID- 29656891
TI  - Timing the Landmark Events in the Evolution of Clear Cell Renal Cell Cancer:
      TRACERx Renal.
AB  - Clear cell renal cell carcinoma (ccRCC) is characterized by near-universal loss
      of the short arm of chromosome 3, deleting several tumor suppressor genes. We
      analyzed whole genomes from 95 biopsies across 33 patients with clear cell renal
      cell carcinoma. We find hotspots of point mutations in the 5' UTR of TERT,
      targeting a MYC-MAX-MAD1 repressor associated with telomere lengthening. The most
      common structural abnormality generates simultaneous 3p loss and 5q gain (36%
      patients), typically through chromothripsis. This event occurs in childhood or
      adolescence, generally as the initiating event that precedes emergence of the
      tumor's most recent common ancestor by years to decades. Similar genomic changes
      drive inherited ccRCC. Modeling differences in age incidence between inherited
      and sporadic cancers suggests that the number of cells with 3p loss capable of
      initiating sporadic tumors is no more than a few hundred. Early development of
      ccRCC follows well-defined evolutionary trajectories, offering opportunity for
      early intervention.

PMID- 29656893
TI  - DNA Repair Network Analysis Reveals Shieldin as a Key Regulator of NHEJ and PARP
      Inhibitor Sensitivity.
AB  - Repair of damaged DNA is essential for maintaining genome integrity and for
      preventing genome-instability-associated diseases, such as cancer. By combining
      proximity labeling with quantitative mass spectrometry, we generated high
      resolution interaction neighborhood maps of the endogenously expressed DNA repair
      factors 53BP1, BRCA1, and MDC1. Our spatially resolved interaction maps reveal
      rich network intricacies, identify shared and bait-specific interaction modules,
      and implicate previously concealed regulators in this process. We identified a
      novel vertebrate-specific protein complex, shieldin, comprising REV7 plus three
      previously uncharacterized proteins, RINN1 (CTC-534A2.2), RINN2 (FAM35A), and
      RINN3 (C20ORF196). Recruitment of shieldin to DSBs, via the ATM-RNF8-RNF168-53BP1
      RIF1 axis, promotes NHEJ-dependent repair of intrachromosomal breaks,
      immunoglobulin class-switch recombination (CSR), and fusion of unprotected
      telomeres. Shieldin functions as a downstream effector of 53BP1-RIF1 in
      restraining DNA end resection and in sensitizing BRCA1-deficient cells to PARP
      inhibitors. These findings have implications for understanding cancer-associated
      PARPi resistance and the evolution of antibody CSR in higher vertebrates.

PMID- 29656896
TI  - Opposite Roles of Salicylic Acid Receptors NPR1 and NPR3/NPR4 in Transcriptional
      Regulation of Plant Immunity.
AB  - Salicylic acid (SA) is a plant defense hormone required for immunity. Arabidopsis
      NPR1 and NPR3/NPR4 were previously shown to bind SA and all three proteins were
      proposed as SA receptors. NPR1 functions as a transcriptional co-activator,
      whereas NPR3/NPR4 were suggested to function as E3 ligases that promote NPR1
      degradation. Here we report that NPR3/NPR4 function as transcriptional co
      repressors and SA inhibits their activities to promote the expression of
      downstream immune regulators. npr4-4D, a gain-of-function npr4 allele that
      renders NPR4 unable to bind SA, constitutively represses SA-induced immune
      responses. In contrast, the equivalent mutation in NPR1 abolishes its ability to
      bind SA and promote SA-induced defense gene expression. Further analysis revealed
      that NPR3/NPR4 and NPR1 function independently to regulate SA-induced immune
      responses. Our study indicates that both NPR1 and NPR3/NPR4 are bona fide SA
      receptors, but play opposite roles in transcriptional regulation of SA-induced
      defense gene expression.

PMID- 29656894
TI  - Deterministic Evolutionary Trajectories Influence Primary Tumor Growth: TRACERx
      Renal.
AB  - The evolutionary features of clear-cell renal cell carcinoma (ccRCC) have not
      been systematically studied to date. We analyzed 1,206 primary tumor regions from
      101 patients recruited into the multi-center prospective study, TRACERx Renal. We
      observe up to 30 driver events per tumor and show that subclonal diversification
      is associated with known prognostic parameters. By resolving the patterns of
      driver event ordering, co-occurrence, and mutual exclusivity at clone level, we
      show the deterministic nature of clonal evolution. ccRCC can be grouped into
      seven evolutionary subtypes, ranging from tumors characterized by early fixation
      of multiple mutational and copy number drivers and rapid metastases to highly
      branched tumors with >10 subclonal drivers and extensive parallel evolution
      associated with attenuated progression. We identify genetic diversity and
      chromosomal complexity as determinants of patient outcome. Our insights reconcile
      the variable clinical behavior of ccRCC and suggest evolutionary potential as a
      biomarker for both intervention and surveillance.

PMID- 29656895
TI  - Tracking Cancer Evolution Reveals Constrained Routes to Metastases: TRACERx
      Renal.
AB  - Clear-cell renal cell carcinoma (ccRCC) exhibits a broad range of metastatic
      phenotypes that have not been systematically studied to date. Here, we analyzed
      575 primary and 335 metastatic biopsies across 100 patients with metastatic
      ccRCC, including two cases sampledat post-mortem. Metastatic competence was
      afforded by chromosome complexity, and we identify 9p loss as a highly selected
      event driving metastasis and ccRCC-related mortality (p = 0.0014). Distinct
      patterns of metastatic dissemination were observed, including rapid progression
      to multiple tissue sites seeded by primary tumors of monoclonal structure. By
      contrast, we observed attenuated progression in cases characterized by high
      primary tumor heterogeneity, with metastatic competence acquired gradually and
      initial progression to solitary metastasis. Finally, we observed early divergence
      of primitive ancestral clones and protracted latency of up to two decades as a
      feature of pancreatic metastases.

PMID- 29656897
TI  - In Silico Labeling: Predicting Fluorescent Labels in Unlabeled Images.
AB  - Microscopy is a central method in life sciences. Many popular methods, such as
      antibody labeling, are used to add physical fluorescent labels to specific
      cellular constituents. However, these approaches have significant drawbacks,
      including inconsistency; limitations in the number of simultaneous labels because
      of spectral overlap; and necessary perturbations of the experiment, such as
      fixing the cells, to generate the measurement. Here, we show that a computational
      machine-learning approach, which we call "in silico labeling" (ISL), reliably
      predicts some fluorescent labels from transmitted-light images of unlabeled fixed
      or live biological samples. ISL predicts a range of labels, such as those for
      nuclei, cell type (e.g., neural), and cell state (e.g., cell death). Because
      prediction happens in silico, the method is consistent, is not limited by
      spectral overlap, and does not disturb the experiment. ISL generates biological
      measurements that would otherwise be problematic or impossible to acquire.

PMID- 29656898
TI  - How to decide which patient-reported outcome measure to use? A practical guide
      for plastic surgeons.
AB  - The use of patient-reported outcome measures (PROMs) is increasing across all
      medical specialties, as their importance to patient care is validated. They are
      likely to play a particularly important role in plastic and reconstructive
      surgery where outcomes are often subjective, and the recent guidance from the
      Royal College of Surgeons of England advising their use in cosmetic surgery
      highlights this. To drive their routine use across our specialty, it is important
      that clinicians are capable of understanding the often complex and confusing
      language that surrounds their design and validation. In this article, we describe
      the process of PROM design and validation, and we attempt to 'demystify' the
      language used in the health outcome literature. We present the important steps
      that a well-designed PROM must go through and suggest a straightforward guide for
      selecting the most appropriate PROMs for use in clinical practice. We hope that
      this will encourage greater use of PROM data across plastic and reconstructive
      surgery and ultimately help improve outcomes for our patients.

PMID- 29656899
TI  - Long-term outcome of patients with or without osseointegrated implants after
      resection of mandibular ameloblastoma and reconstruction with vascularized bone
      graft: Functional assessment and quality of life.
AB  - BACKGROUND: The optimal management after the resection of mandibular
      ameloblastoma has been very challenging to surgeons. The aim of this study is to
      evaluate the functional, aesthetic, and quality of life outcomes of patients who
      had a segmental mandibular resection and immediate reconstruction with or without
      osseointegrated implants. METHOD: Patients' demographics, tumor characteristics,
      treatment, and complications were retrieved. Patients were divided into two
      groups: dental rehabilitated vs. nondental rehabilitated depending on the
      placement of osseointegrated implants followed by an implanted-retained
      prosthesis. Functional outcomes and quality of life were assessed using the
      Performance Status Scale, the University of Washington Quality of Life (UW-QOL)
      scale, and the 14-item Oral Health Impact Profile (OHIP-14). Aesthetic outcome
      was evaluated by patients using a Visual Analog Scale. RESULTS: Thirty-four
      patients were reviewed. Twenty-two patients were included in the dental
      rehabilitated group and 12 in the nondental rehabilitated group. No recurrence of
      the tumor was found during the average follow-up period of 7.4 years. Although
      both groups reported a similar satisfaction in appearance, patients in the dental
      rehabilitated group scored significantly higher in masticatory function and
      "eating in public" (p < 0.01). There were significant differences (p < 0.05)
      regarding "chewing," "activity," and "anxiety" when assessed using the UW-QOL
      scale. Indeed, patients in the dental rehabilitated group showed a definitively
      better outcome in "physical disability" and "psychological discomfort" dimensions
      when assessed using the OHIP-14. CONCLUSION: Vascularized bone graft
      reconstruction followed by immediate or delayed placement of osseointegrated
      implants showed as an ideal and predictable treatment modality for patients with
      ameloblastoma. The results suggested that patients with osseointegrated implants
      had a significantly better masticatory function, improved quality of life, and
      less psychological consequences.

PMID- 29656900
TI  - Risk factors for fecal carriage of IMP-6-producing Enterobacteriaceae at a long
      term care hospital in Japan: A follow-up report from the northern Osaka
      multicentre study group.
AB  - The prevalence of carbapenem-resistant Enterobacteriaceae (CRE) has been
      increasing at medical institutions in Japan without even noticing. Recently, we
      performed a point prevalence survey for CRE carriage at a medical facility in
      northern Osaka that demonstrated an unexpectedly high prevalence of blaIMP-6
      positive CRE, particularly at long-term care hospitals (LTCH). To identify the
      risk factors for CRE carriage, we collected clinical data of patients at a
      representative LTCH. Of 140 patients who were included in this study, 27 (19.3%)
      were colonized with metallo-beta-lactamase (IMP-6) producers. Pulsed-field gel
      electrophoresis of the IMP-6 producing Enterobacteriaceae suggested a non-clonal
      transmission of Escherichia coli, while a clonal spread was shown for Klebsiella
      pneumoniae. Risk factors for CRE colonization were a longer stay at the hospital
      stay and a lower independence state, as measured by Norton scales. We propose
      that a paradigm shift in infection control, inciting a coordinated regional
      effort to involve LTCHs, should be discussed in the aging society of Japan.

PMID- 29656901
TI  - Different rates of progression and mortality in patients with chronic kidney
      disease at outpatient nephrology clinics across Europe.
AB  - The incidence of renal replacement therapy varies across countries. However,
      little is known about the epidemiology of chronic kidney disease (CKD) outcomes.
      Here we describe progression and mortality risk of patients with CKD but not on
      renal replacement therapy at outpatient nephrology clinics across Europe using
      individual data from nine CKD cohorts participating in the European CKD Burden
      Consortium. A joint model assessed the mean change in estimated glomerular
      filtration rate (eGFR) and mortality risk simultaneously, thereby accounting for
      mortality risk when estimating eGFR decline and vice versa, while also correcting
      for the measurement error in eGFR. Results were adjusted for important risk
      factors (baseline eGFR, age, sex, albuminuria, primary renal disease, diabetes,
      hypertension, obesity and smoking) in 27,771 patients from five countries. The
      adjusted mean annual eGFR decline varied from 0.77 (95% confidence interval 0.45,
      1.08) ml/min/1.73m2 in the Belgium cohort to 2.43 (2.11, 2.75) ml/min/1.73m2 in
      the Spanish cohort. As compared to the Italian PIRP cohort, the adjusted
      mortality hazard ratio varied from 0.22 (0.11, 0.43) in the London LACKABO cohort
      to 1.30 (1.13, 1.49) in the English CRISIS cohort. These results suggest that the
      eGFR decline showed minor variation but mortality showed the most variation.
      Thus, different health care organization systems are potentially associated with
      differences in outcome of patients with CKD within Europe. These results can be
      used by policy makers to plan resources on a regional, national and European
      level.

PMID- 29656902
TI  - Legumain, an asparaginyl endopeptidase, mediates the effect of M2 macrophages on
      attenuating renal interstitial fibrosis in obstructive nephropathy.
AB  - Two distinct macrophage phenotypes contribute to kidney injury and repair during
      the progression of renal interstitial fibrosis; proinflammatory (M1) and
      antiinflammatory (M2) macrophages. Legumain, an asparaginyl endopeptidase of the
      cysteine protease family, is overexpressed in macrophages in some pathological
      conditions. However, the macrophage subtype and function of macrophage-derived
      legumain remains unclear. To resolve this we tested whether M2 macrophages
      contribute to the accumulation of legumain in the unilateral ureteral obstruction
      model. Legumain-null mice exhibited more severe fibrotic lesions after
      obstruction compared with wild-type control. In vitro, IL4-stimulated M2
      polarization led to the overexpression and secretion of legumain. The levels of
      fibronectin and collagen I/III, major components of the extracellular matrix,
      were reduced in the conditioned medium of TGF-beta1-stimulated tubular epithelial
      cells or fibroblasts after treatment with legumain or conditioned medium from IL4
      stimulated macrophages. Administration of the legumain inhibitor RR-11a
      exacerbated fibrotic lesions following obstruction. Therapeutically, adoptive
      transfer of legumain-overexpressing macrophages or IL4-stimulated macrophages
      ameliorated the deposition of collagen and fibronectin induced by ureteral
      obstruction, either in the wild-type mice or in lgmn-/- mice. Thus, M2
      macrophages overexpress and secret legumain and legumain mediates the anti
      fibrotic effect of M2 macrophages in obstructive nephropathy.

PMID- 29656904
TI  - Donor-specific hypo-responsiveness occurs in simultaneous liver-kidney transplant
      recipients after the first year.
AB  - Kidney allografts of patients who undergo simultaneous liver-kidney
      transplantation incur less immune-mediated injury, and retain better function
      compared to other kidney allografts. To characterize the host alloimmune
      responses in 28 of these patients, we measured the donor-specific
      alloresponsiveness and phenotypes of peripheral blood cells after the first year.
      These values were then compared to those of 61 similarly immunosuppressed
      recipients of a solitary kidney or 31 recipients of liver allografts. Four
      multicolor, non-overlapping flow cytometry protocols were used to assess the
      immunophenotypes. Mixed cell cultures with donor or third party cells were used
      to measure cell proliferation and interferon gamma production. Despite a
      significant overlap, simultaneous liver-kidney transplant recipients had a lower
      overall frequency of circulating CD8+, activated CD4+ and effector memory T
      cells, compared to solitary kidney transplant recipients. Simultaneous liver
      kidney transplant recipient T cells had a significantly lower proliferative
      response to the donor cells compared to solitary kidney recipients (11.9 vs.
      42.9%), although their response to third party cells was unaltered. The frequency
      of interferon gamma producing alloreactive T cells in simultaneous liver-kidney
      transplant recipients was significantly lower than that of solitary kidney
      transplant recipients. Flow cytometric analysis of the mixed cultures
      demonstrated that both alloreactive CD4+ and CD8+ compartments of the
      simultaneous liver-kidney transplant recipient circulating blood cells were
      smaller. Thus, the phenotypic and functional characteristics of the circulating
      blood cells of the simultaneous liver-kidney transplant recipients resembled
      those of solitary liver transplant recipients, and appear to be associated with
      donor-specific hypo-alloresponsiveness.

PMID- 29656905
TI  - Transcranial direct current stimulation improves long-term memory deficits in an
      animal model of attention-deficit/hyperactivity disorder and modulates oxidative
      and inflammatory parameters.
AB  - BACKGROUND: Transcranial direct current stimulation (tDCS) is a technique that
      modulates neuronal activity and has been proposed as a potential therapeutic tool
      for attention-deficit/hyperactivity disorder (ADHD) symptoms. Although pilot
      studies have shown evidence of efficacy, its mechanism of action remains unclear.
      OBJECTIVE/HYPOTHESIS: We evaluated the effects of tDCS on behavioral (working and
      long-term memory) and neurochemical (oxidative and inflammatory parameters)
      outcomes related to ADHD pathophysiology. We used the most widely accepted animal
      model of ADHD: spontaneously hypertensive rats (SHR). The selected behavioral
      outcomes have been shown to be altered in both ADHD patients and animal models,
      and were chosen for their relation to the proposed mechanistic action of tDCS.
      METHODS: Adult male SHR and their control, the Wistar Kyoto rats (WKY), were
      subjected to 20 min of bicephalic tDCS or sham stimulation for 8 consecutive
      days. Working memory, long-term memory, and neurochemical outcomes were
      evaluated. RESULTS: TDCS improved long-term memory deficits presented by the SHR.
      No change in working memory performance was observed. In the hippocampus, tDCS
      increased both the production of reactive oxygen species in SHR and the levels of
      the antioxidant molecule glutathione in both strains. TDCS also modulated
      inflammatory response in the brains of WKY by downregulating pro-inflammatory
      cytokines. CONCLUSION: TDCS had significant effects that were specific for
      strain, type of behavioral and neurochemical outcomes. The long-term memory
      improvement in the SHR may point to a possible therapeutic role of tDCS in ADHD
      that does not seem to be mediated by inflammatory markers. Additionally, the anti
      inflammatory effects observed in the brain of WKY after tDCS needs to be further
      explored.

PMID- 29656903
TI  - Improving the prognosis of patients with severely decreased glomerular filtration
      rate (CKD G4+): conclusions from a Kidney Disease: Improving Global Outcomes
      (KDIGO) Controversies Conference.
AB  - Patients with severely decreased glomerular filtration rate (GFR) (i.e., chronic
      kidney disease [CKD] G4+) are at increased risk for kidney failure,
      cardiovascular disease (CVD) events (including heart failure), and death.
      However, little is known about the variability of outcomes and optimal
      therapeutic strategies, including initiation of kidney replacement therapy (KRT).
      Kidney Disease: Improving Global Outcomes (KDIGO) organized a Controversies
      Conference with an international expert group in December 2016 to address this
      gap in knowledge. In collaboration with the CKD Prognosis Consortium (CKD-PC) a
      global meta-analysis of cohort studies (n = 264,515 individuals with CKD G4+) was
      conducted to better understand the timing of clinical outcomes in patients with
      CKD G4+ and risk factors for different outcomes. The results confirmed the
      prognostic value of traditional CVD risk factors in individuals with severely
      decreased GFR, although the risk estimates vary for kidney and CVD outcomes. A 2-
      and 4-year model of the probability and timing of kidney failure requiring KRT
      was also developed. The implications of these findings for patient management
      were discussed in the context of published evidence under 4 key themes:
      management of CKD G4+, diagnostic and therapeutic challenges of heart failure,
      shared decision-making, and optimization of clinical trials in CKD G4+ patients.
      Participants concluded that variable prognosis of patients with advanced CKD
      mandates individualized, risk-based management, factoring in competing risks and
      patient preferences.

PMID- 29656906
TI  - Exhibition of stochastic resonance in vestibular tilt motion perception.
AB  - BACKGROUND: Stochastic Resonance (SR) is a phenomenon broadly described as "noise
      benefit". The application of subsensory electrical Stochastic Vestibular
      Stimulation (SVS) via electrodes behind each ear has been used to improve human
      balance and gait, but its effect on motion perception thresholds has not been
      examined. OBJECTIVE: This study investigated the capability of subsensory SVS to
      reduce vestibular motion perception thresholds in a manner consistent with a
      characteristic bell-shaped SR curve. METHODS: We measured upright, head-centered,
      roll tilt Direction Recognition (DR) thresholds in the dark in 12 human subjects
      with the application of wideband 0-30 Hz SVS ranging from +/-0-700 MUA. To
      conservatively assess if SR was exhibited, we compared the proportions of both
      subjective and statistical SR exhibition in our experimental data to proportions
      of SR exhibition in multiple simulation cases with varying underlying SR
      behavior. Analysis included individual and group statistics. RESULTS: As there is
      not an established mathematical definition, three humans subjectively judged that
      SR was exhibited in 78% of subjects. "Statistically significant SR exhibition",
      which additionally required that a subject's DR threshold with SVS be
      significantly lower than baseline (no SVS), was present in 50% of subjects. Both
      percentages were higher than simulations suggested could occur simply by chance.
      For SR exhibitors, defined by subjective or statistically significant criteria,
      the mean DR threshold improved by -30% and -39%, respectively. The largest
      individual improvement was -47%. CONCLUSION: At least half of the subjects were
      better able to perceive passive body motion with the application of subsensory
      SVS. This study presents the first conclusive demonstration of SR in vestibular
      motion perception.

PMID- 29656907
TI  - Opposite effects of lateralised transcranial alpha versus gamma stimulation on
      auditory spatial attention.
AB  - BACKGROUND: Spatial attention relatively increases the power of neural 10-Hz
      alpha oscillations in the hemisphere ipsilateral to attention, and decreases
      alpha power in the contralateral hemisphere. For gamma oscillations (>40 Hz), the
      opposite effect has been observed. The functional roles of lateralised
      oscillations for attention are currently unclear. HYPOTHESIS: If lateralised
      oscillations are functionally relevant for attention, transcranial stimulation of
      alpha versus gamma oscillations in one hemisphere should differentially modulate
      the accuracy of spatial attention to the ipsi-versus contralateral side. METHODS:
      20 human participants performed a dichotic listening task under continuous
      transcranial alternating current stimulation (tACS, vs sham) at alpha (10 Hz) or
      gamma (47 Hz) frequency. On each trial, participants attended to four spoken
      numbers on the left or right ear, while ignoring numbers on the other ear. In
      order to stimulate a left temporo-parietal cortex region, which is known to show
      marked modulations of alpha power during auditory spatial attention, tACS (1 mA
      peak-to-peak amplitude) was applied at electrode positions TP7 and FC5 over the
      left hemisphere. RESULTS: As predicted, unihemispheric alpha-tACS relatively
      decreased the recall of targets contralateral to stimulation, but increased
      recall of ipsilateral targets. Importantly, this spatial pattern of results was
      reversed for gamma-tACS. CONCLUSIONS: Results provide a proof of concept that
      transcranially stimulated oscillations can enhance spatial attention and
      facilitate attentional selection of speech. Furthermore, opposite effects of
      alpha versus gamma stimulation support the view that states of high alpha are
      incommensurate with active neural processing as reflected by states of high
      gamma.

PMID- 29656908
TI  - Factors motivating spontaneous exercise in individuals with schizophrenia
      spectrum disorders.

PMID- 29656909
TI  - Corpus callosum shape and morphology in youth across the psychosis Spectrum.
AB  - The corpus callosum is the largest white matter tract in the human brain
      connecting and coordinating homologous regions of the right and left hemispheres
      and has been strongly implicated in the pathogenesis of psychosis. We
      investigated corpus callosum morphology in a large community cohort of 917
      individuals (aged 8-21), including 267 endorsing subsyndromal or threshold
      psychotic symptoms (207 on the psychosis spectrum and 60 with limited psychosis
      based on previously published criteria) and 650 non-psychotic volunteers. We used
      a highly reliable and previously published algorithm to automatically identify
      the midsagittal plane and to align the corpus callosum along the anterior and
      posterior commissures for segmentation, thereby eliminating these sources of
      error variance in dependent measures, which included perimeter, length, mean
      thickness and shape (circularity). The parcellation scheme divided the corpus
      callosum into 7 subregions that consisted of the rostrum, genu, rostral body,
      anterior midbody, posterior midbody, isthmus, and splenium. Both individuals
      endorsing psychotic symptoms and those with limited psychosis had significantly
      (p<.05) smaller area and lower thickness measures compared to healthy volunteers,
      but did not differ significantly from each other. Findings were relatively
      widespread indicating a relatively global effect not circumscribed to any
      particular corpus callosum subregion. These data are consistent with the
      hypothesis that corpus callosum abnormalities may be evident early in the course
      of illness and predate the onset of frank psychosis. Given that these measures
      can be easily obtained and are highly reliable they may assist in the
      identification of individuals at future risk for psychosis.

PMID- 29656910
TI  - Glycemic control is an important modifiable risk factor for uveitis in patients
      with diabetes: A retrospective cohort study establishing clinical risk and
      ophthalmic disease burden.
AB  - AIM: To characterize the risk uveitis, scleritis or episcleritis in relation to
      diabetes, glycaemic control, and co-existence of retinopathy. METHODS: Using the
      Royal College of General Practitioners Research and Surveillance Centre database,
      we established the prevalence of acute uveitis and scleritis or episcleritis over
      a six-year period among populations without(n = 889,856) and with diabetes(n =
      48,584). We evaluated the impact of glycaemic control on disease risk. Regression
      modeling was used to identify associations, adjusting for clinical and
      demographic confounders. RESULTS: Incidence of acute uveitis was higher among
      patients with diabetes; Type 1 OR:2.01 (95% CI 1.18-3.41; p = 0.009), and Type 2
      OR:1.23 (1.05-1.44; p = 0.01). Glycaemic control was established as an important
      effect modifier for uveitis risk, whereby those with poorer control suffered
      higher disease burden. Results confirmed a dose-response relationship such that
      very poor glycaemic control OR:4.72 (2.58-8.65; p < 0.001), poor control OR:1.57
      (1.05-2.33; p = 0.03) and moderate control OR:1.20 (0.86-1.68; p = 0.29) were
      predictive of uveitis. Similar results were observed when evaluating retinopathy
      staging: proliferative retinopathy OR:2.42 (1.25-4.69; p = 0.01). These results
      were not maintained for scleritis or episcleritis. CONCLUSION: Acute uveitis is
      more common in patients with diabetes; at highest risk are those with type 1
      disease with poor glycaemic control. Glycaemic improvements may prevent
      recurrence.

PMID- 29656912
TI  - The Voices for Healthy Kids and State Legislation to Prevent Childhood Obesity:
      An Update.
AB  - INTRODUCTION: The purpose of this study is to examine general time trends in
      childhood obesity legislative activity in all 50 states (overall and by health
      equity focus) and whether the Voices for Healthy Kids Campaign (Voices) was
      associated with increased legislative activity. METHODS: LexisNexis State Capital
      was used to identify bills related to childhood obesity from 2012 to 2016. Linear
      and linear probability models were used to assess general time trends and
      regression-based difference-in-difference models to assess whether time trends
      differed for states that received a Voices grant. The data were analyzed in 2017.
      RESULTS: A total of 989 bills were introduced (Year 1=304, Year 2=364; Year
      3=321), and a total of 93 bills were enacted (Year 1=34, Year 2=24, Year 3=35)
      after baseline. The mean number of bills introduced (baseline=4.3, Year 1=6.6,
      Year 2=7.3, Year 3=7.0, p=0.007), and the average state enactment rate
      (baseline=11%, Year 1=16%, Year 2=8%, Year 3=27%, p-trend=0.02) increased
      significantly. States with Voices grantees introduced 2.1 more bills than non
      grantee states (p=0.04). The estimated difference over time in bill enactment and
      health equity focus did not differ by Voices grantee status. CONCLUSIONS:
      Childhood obesity bill introduction and enactment increased between 2013 and
      2016. The evidence-based advocacy supported by Voices appears to be significantly
      associated with greater increases in state-level bill introduction, but not
      enactment of legislation to address childhood obesity.

PMID- 29656911
TI  - Healthcare Empowerment and HIV Viral Control: Mediating Roles of Adherence and
      Retention in Care.
AB  - INTRODUCTION: This study assessed longitudinal relationships between patient
      healthcare empowerment, engagement in care, and viral control in the Women's
      Interagency HIV Study, a prospective cohort study of U.S. women living with HIV.
      METHODS: From April 2014 to March 2016, four consecutive 6-month visits were
      analyzed among 973 women to assess the impact of Time 1 healthcare empowerment
      variables (Tolerance for Uncertainty and the state of Informed Collaboration
      Committed Engagement) on Time 2 reports of >=95% HIV medication adherence and not
      missing an HIV primary care appointment since last visit; and on HIV RNA viral
      control across Times 3 and 4, controlling for illicit drug use, heavy drinking,
      depression symptoms, age, and income. Data were analyzed in 2017. RESULTS:
      Adherence of >=95% was reported by 83% of women, 90% reported not missing an
      appointment since the last study visit, and 80% were categorized as having viral
      control. Logistic regression analyses revealed a significant association between
      the Informed Collaboration Committed Engagement subscale and viral control,
      controlling for model covariates (AOR=1.08, p=0.04), but not for the Tolerance
      for Uncertainty subscale and viral control (AOR=0.99, p=0.68). In separate
      mediation analyses, the indirect effect of Informed Collaboration Committed
      Engagement on viral control through adherence (beta=0.04, SE=0.02, 95% CI=0.02,
      0.08), and the indirect effect of Informed Collaboration Committed Engagement on
      viral control through retention (beta=0.01, SE=0.008, 95% CI=0.001, 0.030) were
      significant. Mediation analyses with Tolerance for Uncertainty as the predictor
      did not yield significant indirect effects. CONCLUSIONS: The Informed
      Collaboration Committed Engagement healthcare empowerment component is a
      promising pathway through which to promote engagement in care among women living
      with HIV.

PMID- 29656913
TI  - Faith, Activity, and Nutrition Randomized Dissemination and Implementation Study:
      Countywide Adoption, Reach, and Effectiveness.
AB  - INTRODUCTION: Faith-based organizations can contribute to improving population
      health, but few dissemination and implementation studies exist. This paper
      reports countywide adoption, reach, and effectiveness from the Faith, Activity,
      and Nutrition dissemination and implementation study. DESIGN: This was a group
      randomized trial. Data were collected in 2016. Statistical analyses were
      conducted in 2017. SETTING/PARTICIPANTS: Churches in a rural, medically
      underserved county in South Carolina were invited to enroll, and attendees of
      enrolled churches were invited to complete questionnaires (n=1,308 participated).
      INTERVENTION: Churches (n=59) were randomized to an intervention or control
      (delayed intervention) condition. Church committees attended training focused on
      creating opportunities, setting guidelines/policies, sharing messages, and
      engaging pastors for physical activity (PA) and healthy eating (HE). Churches
      also received 12 months of telephone-based technical assistance. Community health
      advisors provided the training and technical assistance. MAIN OUTCOMES MEASURES:
      The Reach, Efficacy/Effectiveness, Adoption, Implementation, Maintenance (RE-AIM)
      framework guided measurement of adoption and reach. To assess effectiveness,
      church attendees completed post-test only questionnaires of perceptions of church
      environment, PA and fruit and vegetable (FV) self-efficacy, FV intake, and PA.
      Regression models controlled for church clustering and predominant race of
      congregation, as well as member age, gender, education, and self-reported cancer
      diagnosis. RESULTS: Church adoption was 42% (55/132). Estimated reach was 3,527,
      representing 42% of regular church attendees and 15% of county residents.
      Intervention church attendees reported greater church-level PA opportunities, PA
      and HE messages, and PA and HE pastor support (p<0.0001), but not FV
      opportunities (p=0.07). PA self-efficacy (p=0.07) and FV self-efficacy (p=0.21)
      were not significantly higher in attendees of intervention versus control
      churches. The proportion of inactive attendees was lower in intervention versus
      control churches (p=0.02). The proportion meeting FV (p=0.27) and PA guidelines
      (p=0.32) did not differ by group. CONCLUSIONS: This innovative dissemination and
      implementation study had high adoption and reach with favorable environmental
      impacts, positioning it for broader dissemination. TRIAL REGISTRATION: This study
      is registered at www.clinicaltrials.gov NCT02868866.

PMID- 29656914
TI  - Results of an RCT in Two Pediatric Emergency Departments to Evaluate the Efficacy
      of an m-Health Educational App on Car Seat Use.
AB  - INTRODUCTION: The growing interest in incorporating prevention into emergency
      health care make it timely to examine the use of computer technology to
      efficiently deliver effective education in this setting. STUDY DESIGN: This RCT
      compared results from an intervention group (n=367) that received child passenger
      safety information, to an attention-matched control (n=375). A baseline survey
      and two follow-up surveys at 3 and 6 months were conducted. SETTING/PARTICIPANTS:
      Data were collected from June 2014 to September 2016 from a sample of parents
      with children aged 4-7 years recruited from a pediatric emergency department in
      an East Coast urban area and one in a Midwest semi-rural area. INTERVENTION: A
      theory-based, stage-tailored educational program, Safety in Seconds v2.0TM,
      delivered on a mobile app. MAIN OUTCOME MEASURES: Four car seat behaviors: (1)
      having the correct restraint for the child's age and weight; (2) having the child
      ride in the backseat all the time; (3) buckling up the child all the time; and
      (4) having the child's restraint inspected by a child passenger safety
      technician. RESULTS: At 3 months, adjusting for baseline behaviors and attrition,
      the odds of reporting the correct behavior by the intervention group relative to
      the control group was 2.07 (p<0.01) for using the correct car seat; 2.37 (p<0.05)
      times for having the child ride in the back seat; 1.04 (nonsignificant) for
      riding buckled up all the time; and 1.99 (p<0.01) times for having the car seat
      inspected. At 6 months, there were statistically significant effects for
      reporting use of the correct car seat (OR=1.84, p<0.01) and having the car seat
      inspected (OR=1.73, p<0.01). CONCLUSIONS: Mobile apps hold promise for reaching
      large populations with individually tailored child passenger safety education.
      TRIAL REGISTRATION: Clinical Trial Registration # NCT02345941.

PMID- 29656915
TI  - Substance Use and Suicide in Pacific Islander, American Indian, and Multiracial
      Youth.
AB  - INTRODUCTION: National estimates of U.S. Native Hawaiian and other Pacific
      Islander (NHPI), American Indian/Alaskan Native (AIAN), and multiracial
      adolescent substance use and suicidality are scarce because of their small
      population sizes. The aim was to estimate the national prevalence of, and
      disparities in, substance use and suicidality among these understudied
      adolescents. METHODS: Analyses conducted in 2017 of U.S. adolescents (grades
      ninth to 12th) from the 1991-2015 Combined National Youth Behavioral Risk Surveys
      estimated (1) prevalence of lifetime and current (past 30-day) substance use,
      past 12-month depressed mood, and suicidality by racial group; and (2) AORs for
      depressed mood and suicidality regressed on current alcohol, cigarette, and
      marijuana use. RESULTS: Among 184,494 U.S. adolescents, alcohol, cigarettes, and
      marijuana were commonly used with lifetime prevalence of 75.32%, 58.11%, and
      40.55%, respectively, and current prevalence of 44.51%, 24.58%, and 22.01%,
      respectively. Past 12-month prevalence of suicidal thoughts, suicide planning,
      and attempted suicide were 18.87%, 14.75%, and 7.98%, respectively. Relative to
      non-Hispanic whites, NHPI, AIAN, and multiracial adolescents had higher
      prevalence of using many illicit substances (e.g., marijuana, heroin), depressed
      mood, and suicidal thoughts, planning, and attempts (p<0.05). Except for NHPIs
      and current alcohol use, current alcohol and cigarette use were independently
      associated with 2.0-2.3 times greater AORs (p<0.05) for attempted suicide among
      the target adolescents. CONCLUSIONS: U.S. NHPI, AIAN, and multiracial adolescents
      are disproportionately burdened by illicit substance use, depressed mood, and
      suicidality. Current alcohol and cigarette use may predispose these adolescents
      toward suicidality, offering potential pathways to alleviate suicide risk.

PMID- 29656916
TI  - Tobacco Use and Sexual Orientation in a National Cross-sectional Study: Age,
      Race/Ethnicity, and Sexual Identity-Attraction Differences.
AB  - INTRODUCTION: The purpose of this study is to determine the past-year prevalence
      estimates of any nicotine/tobacco use, cigarette smoking, and DSM-5 tobacco use
      disorder based on sexual identity among U.S. adults, and to examine potential
      variations in these estimates by age, race/ethnicity, and sexual identity
      attraction concordance/discordance. METHODS: The 2012-2013 National Epidemiologic
      Survey on Alcohol and Related Conditions collected data via in-person interviews
      with a cross-sectional nationally representative sample of non-institutionalized
      adults (response rate=60.1%) and analyses for the present study were conducted in
      2017. RESULTS: Any past-year nicotine/tobacco use, cigarette smoking, and DSM-5
      tobacco use disorder were most prevalent among sexual minority-identified adults
      compared with heterosexual-identified adults, with notable variations based on
      sex, age, race/ethnicity, and sexual identity-attraction discordance. Elevated
      rates of any nicotine/tobacco use, cigarette smoking, and DSM-5 tobacco use
      disorder among sexual minorities were most prevalent among younger lesbian women
      and gay men, and all age groups of bisexual men and women. The odds of any
      nicotine/tobacco use, cigarette smoking, and DSM-5 tobacco use disorder were
      significantly greater among sexual identity-attraction discordant women and
      significantly lower among sexual identity-attraction discordant men. CONCLUSIONS:
      These findings provide valuable new information about sexual minority subgroups,
      such as self-identified bisexual older adults and sexual identity-attraction
      discordant women, that appear to be at higher risk for adverse smoking-related
      health consequences as a result of their elevated rates of cigarette smoking.
      Additional attention is warranted to examine these high-risk subpopulations
      prospectively and, if the results are replicated with larger samples, this
      information can be used to target smoking-cessation and lung cancer screening
      efforts.

PMID- 29656917
TI  - The Short-Term Impacts of the Philadelphia Beverage Tax on Beverage Consumption.
AB  - INTRODUCTION: On January 1, 2017, Philadelphia implemented a beverage tax of
      $0.015/ounce on sugar ("regular") and sugar-substitute ("diet") beverages. The
      purpose of this study was to evaluate the immediate impact of the tax on
      residents' consumption of soda, fruit drinks, energy drinks, and bottled water.
      METHODS: A repeat cross-sectional study design used data from a random-digit
      dialing phone survey during a no-tax period (December 6-31, 2016) and a tax
      period (January 15-February 31, 2017) among 899 respondents in Philadelphia,
      Pennsylvania, and 878 respondents in three nearby comparison cities. Survey
      questions included frequency and volume of bottled water and beverages. Outcomes
      were daily consumption, and 30-day consumption frequency and volume. Propensity
      score-weighted difference-in-differences regression was used to control for
      secular time trend and confounding. Covariates were sociodemographics, BMI,
      health status, smoking, and alcohol use. Analyses were conducted in 2017.
      RESULTS: Within the first 2 months of tax implementation, relative to the
      comparison cities, in Philadelphia the odds of daily consumption of regular soda
      was 40% lower (OR=0.6, 95% CI=0.37, 0.97); energy drink was 64% lower (OR=0.36,
      95% CI=0.17, 0.76); bottled water was 58% higher (OR=1.58, 95% CI=1.13, 2.20);
      and the 30-day regular soda consumption frequency was 38% lower (ratio of
      consumption frequency=0.62, 95% CI=0.40, 0.98). CONCLUSIONS: Early results
      suggest that the tax influenced daily consumption of regular soda, energy drinks,
      and bottled water. Future studies are needed to evaluate longer-term impact of
      the tax on sugared beverage consumption and substitutions.

PMID- 29656918
TI  - Proximity to Liquor Stores and Adolescent Alcohol Intake: A Prospective Study.
AB  - INTRODUCTION: Cross-sectional studies have reported associations between liquor
      store availability and alcohol use among adolescents, but few prospective studies
      have confirmed this association. The aim of this study was to examine whether
      proximity to liquor stores at age 14 years was associated with alcohol intake at
      ages 14, 17, and 20 years. METHODS: Participants of the Western Australian
      Pregnancy Cohort (Raine) Study (n=999) self-reported alcohol intake at age 14
      years (early adolescence, 2003-2005); age 17 years (middle adolescence, 2006
      2008); and age 20 years (late adolescence, 2009-2011). A GIS measured proximity
      to the closest liquor store from participants' home and school addresses at age
      14 years. Regression analyses in 2017 assessed the relationship between distance
      to the closest liquor store around home, school, or both (<=800 m versus >800 m)
      and alcohol intake. RESULTS: In cross-sectional analyses (age 14 years), having a
      liquor store within 800 m of school was associated with ever having part of an
      alcoholic drink (OR=2.34, p=0.003). Also, having a liquor store within 800 m of
      home or school was associated with ever having part of an alcoholic drink
      (OR=1.49, p=0.029) and ever having engaged in heavy drinking (OR=1.79, p=0.023).
      In prospective analyses, liquor store proximity at age 14 years was a significant
      predictor of alcohol intake at age 17 years (OR=2.34, p=0.032) but not at age 20
      years. CONCLUSIONS: Liquor store availability in early adolescence may be a risk
      factor for alcohol intake in early and middle, but not late, adolescence.
      Improved understanding of the longer-term impacts of liquor store exposure on
      sensitive populations could help inform future licensing regulations.

PMID- 29656919
TI  - Trends and Gaps in Awareness of Direct-to-Consumer Genetic Tests From 2007 to
      2014.
AB  - INTRODUCTION: Direct-to-consumer genetic tests for inherited disease risks have
      gained recent approvals from the Food and Drug Administration, and interest in
      these tests has continued to grow. Broad use of these tests coupled with planning
      and discussion with health providers regarding genetic risks and potential
      protective behavior changes have been proposed as preventive tools to reduce
      health disparities and improve equity in health outcomes. However, awareness of
      direct-to-consumer genetic testing has historically demonstrated differences by
      education, income, and race; these disparities could jeopardize potential
      benefits by limiting access and use. METHODS: The national survey data from the
      Health Information National Trends Survey was analyzed to understand how overall
      awareness of direct-to-consumer genetic testing and disparities in awareness
      across sociodemographic groups have changed since 2007. RESULTS: The findings
      showed persistent disparities, as well as a widening gap in awareness between
      Hispanics and non-Hispanic whites (OR2007 =1.52, OR2014 =0.58, pchange =0.0056),
      despite overall increases in awareness over time. CONCLUSIONS: Given these
      findings, policies regulating direct-to-consumer genetic tests should prioritize
      equitable distribution of benefits by including provisions that counteract
      prevailing disparities in awareness.

PMID- 29656920
TI  - Effect of Smoking on Periodontitis: A Systematic Review and Meta-regression.
AB  - CONTEXT: The study systematically reviewed articles on the association between
      tobacco smoking and periodontitis, as it has been hypothesized that smoking
      affects the course of periodontitis through impairment of immunological and
      vascular mechanisms. EVIDENCE ACQUISITION: Searches of articles indexed in
      PubMed, Scopus, and Embase were performed up to and including May 2017. Search
      strategy included MeSH and free terms: periodontitis, periodontal diseases,
      smoking, tobacco use, tobacco, tobacco products, cigarette, pipe, and cigar. Only
      original prospective longitudinal studies that investigated the association
      between smoking and periodontitis incidence or progression were included. Results
      were shown as combined risk ratio. Meta-regression and subgroup analyses were
      used to explore potential sources of heterogeneity. Analyses were conducted in
      August 2017. EVIDENCE SYNTHESIS: Twenty-eight studies were included in the
      review; of these, only 14 presented data that could be included in the meta
      analysis. Pooled adjusted risk ratios estimate that smoking increases the risk of
      periodontitis by 85% (risk ratio=1.85, 95% CI=1.5, 2.2). Meta-regression
      demonstrated that age explained 54.2% of the variability between studies, time of
      follow-up explained 13.5%, loss to follow-up 10.7%, criteria used to assess the
      periodontal status explained 2.1%, and severity of periodontitis explained 16.9%.
      CONCLUSIONS: Smoking has a detrimental effect on the incidence and progression of
      periodontitis. Tobacco smoking, therefore, is important information that should
      be assessed along with other risk factors for periodontitis.

PMID- 29656921
TI  - Controversy: Pros and cons screening of corticotropic deficiency after exogenous
      glucocorticoid therapy.

PMID- 29656922
TI  - Complete and thorough evaluation is critical for the initiation of surgery in the
      management of women with pelvic floor disorders.

PMID- 29656923
TI  - Structural Basis of Splicing Modulation by Antitumor Macrolide Compounds.
AB  - SF3B is a multi-protein complex essential for branch site (BS) recognition and
      selection during pre-mRNA splicing. Several splicing modulators with antitumor
      activity bind SF3B and thereby modulate splicing. Here we report the crystal
      structure of a human SF3B core in complex with pladienolide B (PB), a macrocyclic
      splicing modulator and potent inhibitor of tumor cell proliferation. PB stalls
      SF3B in an open conformation by acting like a wedge within a hinge, modulating
      SF3B's transition to the closed conformation needed to form the BS adenosine
      binding pocket and stably accommodate the BS/U2 duplex. This work explains the
      structural basis for the splicing modulation activity of PB and related
      compounds, and reveals key interactions between SF3B and a common pharmacophore,
      providing a framework for future structure-based drug design.

PMID- 29656924
TI  - Cell-Cycle Modulation of Transcription Termination Factor Sen1.
AB  - Many non-coding transcripts (ncRNA) generated by RNA polymerase II in S.
      cerevisiae are terminated by the Nrd1-Nab3-Sen1 complex. However, Sen1 helicase
      levels are surprisingly low compared with Nrd1 and Nab3, raising questions
      regarding how ncRNA can be terminated in an efficient and timely manner. We show
      that Sen1 levels increase during the S and G2 phases of the cell cycle, leading
      to increased termination activity of NNS. Overexpression of Sen1 or failure to
      modulate its abundance by ubiquitin-proteasome-mediated degradation greatly
      decreases cell fitness. Sen1 toxicity is suppressed by mutations in other
      termination factors, and NET-seq analysis shows that its overexpression leads to
      a decrease in ncRNA production and altered mRNA termination. We conclude that
      Sen1 levels are carefully regulated to prevent aberrant termination. We suggest
      that ncRNA levels and coding gene transcription termination are modulated by Sen1
      to fulfill critical cell cycle-specific functions.

PMID- 29656925
TI  - Dynamics of PARKIN-Dependent Mitochondrial Ubiquitylation in Induced Neurons and
      Model Systems Revealed by Digital Snapshot Proteomics.
AB  - Flux through kinase and ubiquitin-driven signaling systems depends on the
      modification kinetics, stoichiometry, primary site specificity, and target
      abundance within the pathway, yet we rarely understand these parameters and their
      spatial organization within cells. Here we develop temporal digital snapshots of
      ubiquitin signaling on the mitochondrial outer membrane in embryonic stem cell
      derived neurons, and we model HeLa cell systems upon activation of the PINK1
      kinase and PARKIN ubiquitin ligase by proteomic counting of ubiquitylation and
      phosphorylation events. We define the kinetics and site specificity of PARKIN
      dependent target ubiquitylation, and we demonstrate the power of this approach to
      quantify pathway modulators and to mechanistically define the role of PARKIN UBL
      phosphorylation in pathway activation in induced neurons. Finally, through
      modulation of pS65-Ub on mitochondria, we demonstrate that Ub hyper
      phosphorylation is inhibitory to mitophagy receptor recruitment, indicating that
      pS65-Ub stoichiometry in vivo is optimized to coordinate PARKIN recruitment via
      pS65-Ub and mitophagy receptors via unphosphorylated chains.

PMID- 29656926
TI  - Resting state cerebral blood flow with arterial spin labeling MRI in developing
      human brains.
AB  - The development of brain circuits is coupled with changes in neurovascular
      coupling, which refers to the close relationship between neural activity and
      cerebral blood flow (CBF). Studying the characteristics of CBF during resting
      state in developing brain can be a complementary way to understand the functional
      connectivity of the developing brain. Arterial spin labeling (ASL), as a
      noninvasive MR technique, is particularly attractive for studying cerebral
      perfusion in children and even newborns. We have collected pulsed ASL data in
      resting state for 47 healthy subjects from young children to adolescence (aged
      from 6 to 20 years old). In addition to studying the developmental change of
      static CBF maps during resting state, we also analyzed the CBF time series to
      reveal the dynamic characteristics of CBF in differing age groups. We used the
      seed-based correlation analysis to examine the temporal relationship of CBF time
      series between the selected ROIs and other brain regions. We have shown the
      developmental patterns in both static CBF maps and dynamic characteristics of
      CBF. While higher CBF of default mode network (DMN) in all age groups supports
      that DMN is the prominent active network during the resting state, the CBF
      connectivity patterns of some typical resting state networks show distinct
      patterns of metabolic activity during the resting state in the developing brains.

PMID- 29656927
TI  - Pontocerebellar hypoplasia type 1 for the neuropediatrician: Genotype-phenotype
      correlations and diagnostic guidelines based on new cases and overview of the
      literature.
AB  - Pontocerebellar hypoplasia type 1 (PCH1) is a major cause of non-5q spinal
      muscular atrophy (SMA). We screened 128 SMN1-negative SMA patients from Bulgaria
      for a frequent mutation -p.G31A in EXOSC3, and performed a literature review of
      all genetically verified PCH1 cases. Homozygous p.G31A/EXOSC3 mutation was
      identified in 14 Roma patients, representing three fourths of all our SMN1
      negative Roma SMA cases. The phenotype of the p.G31A/EXOSC3 homozygotes was
      compared to the clinical presentation of all reported to date genetically
      verified PCH1 cases. Signs of antenatal onset of disease present at birth were
      common in all PCH1 sub-types except in the homozygous p.D132A/EXOSC3 patients.
      The PCH1sub-types with early death (between ages 1 day and 17 months), seen in
      patients with p.G31A/EXOSC3 or SLC25A46 mutations have a SMA type 1-like clinical
      presentation but with global developmental delay, visual and hearing impairment,
      with or without microcephaly, nystagmus and optic atrophy. Mutations with milder
      presentation (homozygous p.D132A/EXOSC3 or VRK1) may display additionally signs
      of upper motor neuron impairment, dystonia or ataxia and die at age between 5 and
      18 years. Other EXOSC3 mutations and EXOSC8 cases are intermediate - SMA type 1
      like presentation, spasticity (mostly in EXOSC8) and death between 3 months and 5
      years. There is no correlation between neurological onset and duration of life.
      We add marble-like skin and congenital laryngeal stridor as features of PCH1. We
      show that imaging signs of cerebellar and pontine hypoplasia may be missing early
      in infancy. EMG signs of anterior horn neuronopathy may be missing in PCH1
      patients with SLC25A46 mutations. Thus, there is considerable phenotypic
      variability in PCH1, with some cases being more SMA-like, than PCH-like. Detailed
      clinical evaluation and ethnicity background may guide genetic testing and
      subsequent genetic counseling.

PMID- 29656928
TI  - Benign paroxysmal migraine variants of infancy and childhood: Transitions and
      clinical features.
AB  - INTRODUCTION: Migraine variant disorders of childhood include benign paroxysmal
      torticollis of infancy (BPTI) and benign paroxysmal vertigo of childhood (BPVC).
      This study aimed to review our experience with BPTI and BPVC and determine the
      incidence of children transitioning between each of these disorders and to
      vestibular migraine (VM). METHODS: We retrospectively reviewed the medical
      records of patients seen at the Balance and Vestibular Program at Boston
      Children's Hospital between January 2012 and December 2016 who were diagnosed
      with BPTI, BPVC, and/or VM. RESULTS: Fourteen patients were diagnosed with BPTI,
      39 with BPVC, and 100 with VM. Abnormal rotary chair testing was associated with
      progression from BPTI to BPVC (n = 8, p = 0.045). Eight (57.1%) patients with
      BPTI and 11 (28.2%) with BPVC had motor delay. Eleven (78.6%) patients with BPTI
      and 21 (53.8%) with BPVC had balance impairment. Six BPTI patients developed BPVC
      (42.9%), six BPVC patients developed VM (15.4%), and two patients progressed
      through all three disorders (2%). One BPTI patient progressed directly to VM.
      DISCUSSION: Most patients with BPTI will experience complete resolution in early
      childhood, but some will progress to BPVC, and similarly many patients with BPVC
      will progress to VM. Parents of children with these disorders should be made
      aware of this phenomenon, which we refer to as "the vestibular march." Children
      with BPTI and BPVC should also be screened for hearing loss, otitis media, and
      motor delay.

PMID- 29656929
TI  - Tephrochronology of Bed II, Olduvai Gorge, Tanzania, and placement of the Oldowan
      Acheulean transition.
AB  - Tuffaceous marker beds, derived from volcanic products from the Ngorongoro
      Volcanic Highlands, help define a stratigraphic framework for the world-renowned
      fossil and stone tool record exposed at Olduvai Gorge, Tanzania. However,
      previous efforts to constrain this tuff record, especially for Olduvai Bed II,
      have been limited because of erosion, contamination, reworking, and the
      alteration of volcanic glass under saline-alkaline conditions. This paper applies
      previously defined geochemical and mineralogical "fingerprints" for several major
      Bed II marker tuffs, based on glass (where available) and phenocrysts more
      resistant to alteration (feldspar, hornblende, augite, and titanomagnetite), to
      tuffs from stratigraphic sections in the Olduvai Junction Area, including
      previously and recently excavated Acheulean and Oldowan sites (HWK EE (Locality
      (Loc) 42), EF-HR (Loc 12a), FLK (Loc 45), and MNK (Loc 88)). The Middle Bed II
      Bird Print Tuff (BPT) is found to be more compositionally variable than
      previously reported but is still valuable as a stratigraphic marker over short
      distances. The confirmation of blocks of Tuff IID in conglomerate helps constrain
      Upper Bed II stratigraphy at sites where in-situ tuffs are absent. This paper
      also compiles the results of published geochronological research, providing
      stratigraphic context and updating previously reported dates using a consistent
      40Ar/39Ar reference standard age. The results of this work support the following
      paleoanthropologically relevant conclusions: 1) the early Acheulean site EF-HR
      (Loc 12a) is situated above the level of Hay's Tuff IIC, and thus sits in Upper
      rather than Middle Bed II, (2) the HWK EE (Loc 42) Oldowan site is constrained
      between Tuff IIA and Tuff IIB, just above the boundary between Lower and Middle
      Bed II, and 3) the Acheulean site at FLK W most likely lies within the Middle
      Augitic Sandstone, above Tuff IIB, similar to the placements by Leakey and Hay
      for the earliest Acheulean at Olduvai.

PMID- 29656930
TI  - DNA N6-Adenine Methylation in Arabidopsis thaliana.
AB  - DNA methylation on N6-adenine (6mA) has recently been found to be a potentially
      epigenetic mark in several unicellular and multicellular eukaryotes. However, its
      distribution patterns and potential functions in land plants, which are primary
      producers for most ecosystems, remain largely unknown. Here we report global
      profiling of 6mA sites at single-nucleotide resolution in the genome of
      Arabidopsis thaliana at different developmental stages using single-molecule real
      time sequencing. 6mA sites are widely distributed across the Arabidopsis genome
      and enriched over the pericentromeric heterochromatin regions. 6mA occurs more
      frequently in gene bodies than intergenic regions. Analysis of 6mA methylomes and
      RNA sequencing data demonstrates that 6mA frequency positively correlates with
      the gene expression level and the transition from vegetative to reproductive
      growth in Arabidopsis. Our results uncover 6mA as a DNA mark associated with
      actively expressed genes in Arabidopsis, suggesting that 6mA serves as a hitherto
      unknown epigenetic mark in land plants.

PMID- 29656932
TI  - A Higher-Calorie Refeeding Protocol Does Not Increase Adverse Outcomes in Adult
      Patients with Eating Disorders.
AB  - BACKGROUND: Patients with eating disorders (EDs) are often considered a high-risk
      population to refeed. Current research advises using "start low, go slow"
      refeeding methods (~1,000 kcal/day, advancing ~500 kcal/day every 3 to 4 days) in
      adult patients with severe EDs to prevent the development of refeeding syndrome
      (RFS), typically characterized by decreases in serum electrolyte levels and fluid
      shifts. OBJECTIVE: To compare the incidence of RFS and related outcomes using a
      low-calorie protocol (LC) (1,000 kcal) or a higher-calorie protocol (HC) (1,500
      kcal) in medically compromised adult patients with EDs. DESIGN: This was a
      retrospective pre-test-post-test study. PARTICIPANTS/SETTING: One hundred and
      nineteen participants with EDs, medically admitted to a tertiary hospital in
      Brisbane, Australia, between December 2010 and January 2017, were included (LC:
      n=26, HC: n=93). The HC refeeding protocol was implemented in September 2013.
      MAIN OUTCOME MEASURES: Differences in prevalence of electrolyte disturbances,
      hypoglycemia, edema, and RFS diagnoses were examined. STATISTICAL ANALYSIS
      PERFORMED: chi2 tests, Kruskal-Wallis H test, analysis of variance, and
      independent t tests were used to compare data between the two protocols. RESULTS:
      Descriptors were similar between groups (LC: 28+/-9 years, 96% female, 85% with
      anorexia nervosa, 31% admitted primarily because of clinical symptoms of
      exacerbated ED vs HC: 27+/-9 years, 97% female, 84% with anorexia nervosa, 44%
      admitted primarily because of clinical symptoms of exacerbated ED, P>0.05).
      Participants refed using the LC protocol had higher incidence rates of
      hypoglycemia (LC: 31% vs HC: 10%, P=0.012), with no statistical or clinical
      differences in electrolyte disturbances (LC: 65% vs HC: 45%, P=0.079), edema (LC:
      8% vs HC: 6%, P=0.722) or diagnosed RFS (LC: 4% vs HC: 1%, P=0.391). CONCLUSIONS:
      A higher-calorie refeeding protocol appears to be safe, with no differences in
      rates of electrolyte disturbances or clinically diagnosed RFS and a lower
      incidence of hypoglycemia. Future research examining higher-calorie intakes,
      similar to those studied in adolescent patients, may be beneficial.

PMID- 29656933
TI  - Body Composition Measurement in Bronchiectasis: Comparison between Bioelectrical
      Impedance Analysis, Skinfold Thickness Measurement, and Dual-Energy X-ray
      Absorptiometry before and after Pulmonary Rehabilitation.
AB  - BACKGROUND: In individuals with bronchiectasis, fat-free mass depletion may be
      common despite a low prevalence of underweight and is considered a risk factor
      for increased morbidity and mortality. Techniques to adequately estimate fat-free
      mass and its changes over time are needed. OBJECTIVE: The purpose of this study
      was to assess agreement among values obtained with three different body
      composition techniques: skinfold thickness measurement (STM), bioelectrical
      impedance analysis (BIA), and dual-energy x-ray absorptiometry (DXA). DESIGN: The
      study was a secondary analysis of data from a randomized controlled trial.
      PARTICIPANTS/SETTING: A respiratory rehabilitation program was administered for 3
      months to individuals with bronchiectasis from the bronchiectasis unit of the
      Regional University Hospital in Malaga, Spain, from September 2013 to September
      2014. Individuals with a body mass index (calculated as kg/m2) >18.5 who were
      aged 65 years or younger and those with a body mass index >20 who were older than
      65 years were included. MAIN OUTCOME MEASURES: At baseline and at 3 and 6 months,
      body composition was determined by DXA and STM. STATISTICAL ANALYSES PERFORMED:
      Statistical concordance was assessed with the intraclass correlation coefficient
      (ICC), kappa coefficient, and the degree of agreement using the Bland Altman
      method. For comparison of the quantitative variables at baseline vs at 3 months
      and 6 months, the paired sample t test (or the Wilcoxon test) was used. RESULTS:
      Thirty participants were included. Strong agreement was observed between body
      composition values determined by BIA and DXA in fat mass (ICC: 0.92) and fat-free
      mass (ICC: 0.87). Strong agreement was observed between STM and DXA in the values
      for fat-free mass (ICC: 0.91) and fat mass (ICC: 0.94), and lower agreement was
      observed for the longitudinal data and in the regional values. The mean
      difference between fat-free mass determined by BIA and DXA was + 4.7 with a
      standard deviation of 2.4 kg in favor of BIA. The mean difference between fat
      free mass determined by STM and DXA was +2.3 with a standard deviation of 2.7 kg
      in favor of STM. Six individuals were classified as having a low fat-free mass
      index (20%) by DXA vs four by STM (13%; kappa: 0.76) and only two by BIA (6.6%;
      kappa: 0.44) compared with DXA. CONCLUSIONS: Despite good statistical agreement
      among values obtained with DXA, STM, and BIA, the study findings indicate that
      STM and BIA, above all, tended to overestimate fat-free mass compared with DXA.

PMID- 29656931
TI  - Synaptotagmin 4 Regulates Pancreatic beta Cell Maturation by Modulating the Ca2+
      Sensitivity of Insulin Secretion Vesicles.
AB  - Islet beta cells from newborn mammals exhibit high basal insulin secretion and
      poor glucose-stimulated insulin secretion (GSIS). Here we show that beta cells of
      newborns secrete more insulin than adults in response to similar intracellular
      Ca2+ concentrations, suggesting differences in the Ca2+ sensitivity of insulin
      secretion. Synaptotagmin 4 (Syt4), a non-Ca2+ binding paralog of the beta cell
      Ca2+ sensor Syt7, increased by ~8-fold during beta cell maturation. Syt4 ablation
      increased basal insulin secretion and compromised GSIS. Precocious Syt4
      expression repressed basal insulin secretion but also impaired islet
      morphogenesis and GSIS. Syt4 was localized on insulin granules and Syt4 levels
      inversely related to the number of readily releasable vesicles. Thus,
      transcriptional regulation of Syt4 affects insulin secretion; Syt4 expression is
      regulated in part by Myt transcription factors, which repress Syt4 transcription.
      Finally, human SYT4 regulated GSIS in EndoC-betaH1 cells, a human beta cell line.
      These findings reveal the role that altered Ca2+ sensing plays in regulating beta
      cell maturation.

PMID- 29656934
TI  - Reliability and Validity of Digital Imagery Methodology for Measuring Starting
      Portions and Plate Waste from School Salad Bars.
AB  - BACKGROUND: Scientifically sound methods for investigating dietary consumption
      patterns from self-serve salad bars are needed to inform school policies and
      programs. OBJECTIVE: To examine the reliability and validity of digital imagery
      for determining starting portions and plate waste of self-serve salad bar
      vegetables (which have variable starting portions) compared with manual weights.
      DESIGN/METHODS: In a laboratory setting, 30 mock salads with 73 vegetables were
      made, and consumption was simulated. Each component (initial and removed portion)
      was weighed; photographs of weighed reference portions and pre- and post
      consumption mock salads were taken. Seven trained independent raters visually
      assessed images to estimate starting portions to the nearest 1/4 cup and
      percentage consumed in 20% increments. These values were converted to grams for
      comparison with weighed values. STATISTICAL ANALYSES: Intraclass correlations
      between weighed and digital imagery-assessed portions and plate waste were used
      to assess interrater reliability and validity. Pearson's correlations between
      weights and digital imagery assessments were also examined. Paired samples t
      tests were used to evaluate mean differences (in grams) between digital imagery
      assessed portions and measured weights. RESULTS: Interrater reliabilities were
      excellent for starting portions and plate waste with digital imagery. For
      accuracy, intraclass correlations were moderate, with lower accuracy for
      determining starting portions of leafy greens compared with other vegetables.
      However, accuracy of digital imagery-assessed plate waste was excellent. Digital
      imagery assessments were not significantly different from measured weights for
      estimating overall vegetable starting portions or waste; however, digital imagery
      assessments slightly underestimated starting portions (by 3.5 g) and waste (by
      2.1 g) of leafy greens. CONCLUSIONS: This investigation provides preliminary
      support for use of digital imagery in estimating starting portions and plate
      waste from school salad bars. Results might inform methods used in empirical
      investigations of dietary intake in schools with self-serve salad bars.

PMID- 29656935
TI  - A review of interventions >= 6 months by pharmacists on adherence to medicines in
      cardiovascular disease; characteristics of what works and what doesn't.
AB  - BACKGROUND: Nonadherence to cardiovascular medicines occurs in 60% of subjects
      with chronic cardiovascular disease and leads to poor outcomes. In an attempt to
      improve adherence and cardiovascular outcomes, interventions are often used.
      Interventions may involve a pharmacist, but it is not always clear whether these
      are effective. OBJECTIVES: The primary objective of this review is to determine
      whether interventions by pharmacists, alone, discussing adherence to medicines,
      improve adherence to medicines for cardiovascular disease. Subsequently, the
      review links the characteristics of the individual studies with effectiveness or
      lack of effect. The second objective of this review is to consider whether any
      improvement in adherence with interventions by pharmacist is associated with
      better clinical outcomes. METHODS: A literature search of PubMed and CINAHL for
      'pharmacist', 'medicine' with 'adherence' or 'compliance' or 'persistence' was
      undertaken. To be included in this review, papers had to be of a pharmacist
      working alone and in person in an intervention of subjects with hypertension,
      hyperlipidemia (prior to or after a coronary artery event) or heart failure. The
      paper had to be published in a peer review journal, with a measure of adherence
      to medicines. The effectiveness of the intervention had to be evaluated after >=6
      months. RESULTS: Only 3 out of 8 interventions by pharmacists in hypertension,
      and 5 out of 12 interventions in subjects with hyperlipidemia led to improved
      adherence to medicines. In contrast, all 6 interventions by a pharmacist in
      subjects with heart failure were successful in improving adherence. One
      characteristic of successful interventions by pharmacists to improve adherence to
      cardiovascular medicines is that they must be more than brief/single
      interventions. A second characteristic is that the intervention should not
      involve subjects who are already highly adherent, as it is unlikely adherence can
      be improved in this population. Only 2 of 3 successful interventions in
      hypertension were associated with small reductions in blood pressure, and only
      one intervention in hyperlipidemia was shown to decrease LDL-cholesterol to a
      small extent. In subjects with heart failure, 5 of the 6 successful studies of
      the successful interventions by pharmacists to increase adherence also showed
      improved clinical outcomes. CONCLUSIONS: When planning an intervention to improve
      adherence to medicines and cardiovascular outcomes in subjects with hypertension
      or hyperlipidemic, by a pharmacist alone, or as part of a multi-faceted
      interventions, it is essential to use an intervention that has been shown to be
      effective, as most interventions are not effective at improving adherence or only
      improve adherence and clinical outcomes to a small extent. In heart failure,
      there is well documented evidence of interventions by pharmacists that do improve
      clinical outcomes, which should be adopted widely.

PMID- 29656936
TI  - How patients should be counseled on adverse drug reactions: Avoiding the nocebo
      effect.

PMID- 29656937
TI  - MynxGrip(r) vascular closure device versus manual compression for hemostasis of
      percutaneous transfemoral venous access closure: Results from a prospective
      multicenter randomized study.
AB  - PURPOSE: Evaluate the safety of MynxGrip(r) for common femoral vein closure.
      METHODS AND MATERIALS: This is a multicenter, randomized, prospective study of
      208 patients who were slated to undergo diagnostic/interventional procedures via
      femoral venous access. Patients were randomized 1:1 to receive venous hemostasis
      via MynxGrip(r) (n = 104) or manual compression (n = 104) utilizing 5, 6, and 7
      Fr sheaths. Bilateral calf and thigh circumferences were measured serially.
      Patients were followed up through hospital discharge. There were no differences
      in the baseline characteristics between the two groups. RESULTS: There was no
      difference between the groups for venous thrombosis, (0%, p = 1). Overall, there
      was no significant change in access site calf (-0.18 +/- 1.38 cm, p = 0.18) or
      thigh diameter (0.33 +/- 2.86, p = 0.81). In both groups, none of the patients
      had major or minor vascular complications, access site infection, nerve injury,
      or access site bleeding requiring transfusion. The pre- to post-procedure
      hemoglobin drop was -0.51 +/- 1.1 vs. -0.64 +/- 1.3 g/dL, p = 0.59 in the manual
      compression group and MynxGrip(r) group, respectively. Time to hemostasis, was
      significantly lower in the MynxGrip(r) group compared to the manual compression
      group with 0.12 +/- 0.89 vs. 7.6 +/- 5.7 min, respectively (p < 0.001).
      CONCLUSIONS: The MynxGrip(r) extravascular sealant is safe and effective for
      femoral venous access site closure.

PMID- 29656938
TI  - Vitamin D deficiency and periprocedural myocardial infarction in patients
      undergoing percutaneous coronary interventions.
AB  - Vitamin D deficiency has been implicated in the progression of atherosclerosis
      and acute thrombotic events. We aimed at evaluating the impact of vitamin D
      deficiency on periprocedural myocardial infarction (PMI) in patients undergoing
      percutaneous coronary interventions (PCI). We included 934 patients undergoing
      non-urgent PCI. Assessment of myocardial biomarkers was performed from 6 to 48 h
      after PCI. PMI was defined as Creatine Kinase-MB increase by 3 times the Upper
      Limit Normal or by 50% of an elevated baseline value, periprocedural myocardial
      damage as Troponin I increase by 3 * ULN or 50% of baseline. Patients were
      divided according to vitamin D tertiles values (<10.2 ng/ml; 10.2-18.7 ng/ml;
      >=18.8 ng/ml). Lower tertiles values of vitamin D were associated with age (p =
      0.04), female gender, (p = 0.001), and a higher cardiovascular risk profile.
      Lower vitamin D levels related with PCI of descending anterior coronary artery or
      bypass vein grafts (p = 0.03), treatment of bifurcations (p = 0.05) and side
      branch loss (p = 0.05) and inversely with direct stenting (p = 0.002). However,
      lower vitamin D levels did not influence the risk of PMI (adjusted OR [95% CI] =
      0.81[0.65,1.18], p = 0.09) or periprocedural myocardial damage (adjusted OR [95%
      CI] = 0.93[0.77,1.13], p = 0.48). Similar results were achieved when considering
      the severity of vitamin D deficiency. Therefore, in patients undergoing PCI, no
      association was observed between vitamin D deficiency and the risk of
      periprocedural MI and myocardial damage.

PMID- 29656939
TI  - Management of Metastatic Collecting Duct Carcinoma: An Encouraging Result in a
      Patient Treated With Cabozantinib.

PMID- 29656940
TI  - Somatostatin Receptor Expression in Renal Cell Carcinoma-A New Front in the
      Diagnostics and Treatment of Renal Cell Carcinoma.

PMID- 29656942
TI  - Evolving Industry Partnerships and Investments in Cell and Gene Therapies.
AB  - Cell and gene therapies hold the promise of providing significant and durable
      health gains to patients in many disease states and have recently elicited
      significant investor and partner interest. We cover the current state of industry
      partnerships and investments, highlight what makes a partnership advantageous,
      and discuss implications for stem cell therapies.

PMID- 29656941
TI  - Submucosal Gland Myoepithelial Cells Are Reserve Stem Cells That Can Regenerate
      Mouse Tracheal Epithelium.
AB  - The mouse trachea is thought to contain two distinct stem cell compartments that
      contribute to airway repair-basal cells in the surface airway epithelium (SAE)
      and an unknown submucosal gland (SMG) cell type. Whether a lineage relationship
      exists between these two stem cell compartments remains unclear. Using lineage
      tracing of glandular myoepithelial cells (MECs), we demonstrate that MECs can
      give rise to seven cell types of the SAE and SMGs following severe airway injury.
      MECs progressively adopted a basal cell phenotype on the SAE and established
      lasting progenitors capable of further regeneration following reinjury. MECs
      activate Wnt-regulated transcription factors (Lef-1/TCF7) following injury and
      Lef-1 induction in cultured MECs promoted transition to a basal cell phenotype.
      Surprisingly, dose-dependent MEC conditional activation of Lef-1 in vivo promoted
      self-limited airway regeneration in the absence of injury. Thus, modulating the
      Lef-1 transcriptional program in MEC-derived progenitors may have regenerative
      medicine applications for lung diseases.

PMID- 29656944
TI  - Amyloidosis as a Cause of Cystic Pulmonary Fibrosis Associated With Pulmonary
      Nodules.

PMID- 29656943
TI  - Myoepithelial Cells of Submucosal Glands Can Function as Reserve Stem Cells to
      Regenerate Airways after Injury.
AB  - Cells demonstrate plasticity following injury, but the extent of this phenomenon
      and the cellular mechanisms involved remain underexplored. Using single-cell RNA
      sequencing (scRNA-seq) and lineage tracing, we uncover that myoepithelial cells
      (MECs) of the submucosal glands (SMGs) proliferate and migrate to repopulate the
      airway surface epithelium (SE) in multiple injury models. Specifically, SMG
      derived cells display multipotency and contribute to basal and luminal cell types
      of the SMGs and SE. Ex vivo expanded MECs have the potential to repopulate and
      differentiate into SE cells when grafted onto denuded airway scaffolds.
      Significantly, we find that SMG-like cells appear on the SE of both extra- and
      intra-lobular airways of large animal lungs following severe injury. We find that
      the transcription factor SOX9 is necessary for MEC plasticity in airway
      regeneration. Because SMGs are abundant and present deep within airways, they may
      serve as a reserve cell source for enhancing human airway regeneration.

PMID- 29656945
TI  - Ketamine versus ketamine pluses atropine for pediatric sedation: A meta-analysis.
AB  - OBJECTIVES: The application of atropine for pediatric sedation in the emergency
      department remains controversial. Our objective was to perform a comprehensive
      review of the literature and assess the clinical indexes in groups with and
      without atropine use. METHODS: PubMed, EMBASE, and the Cochrane Library were
      searched for randomized and non-randomized studies that compared ketamine and
      ketamine plus atropine for pediatric sedation. The risk ratio with 95% confidence
      interval was calculated using either a fixed- or random-effects model according
      to the value of I2. RESULTS: One retrospective study and four randomized
      controlled trials were identified to compare the clinical indexes. For the
      clinical indexes, the ketamine plus atropine group had better outcomes than the
      ketamine group in hypersalivation (P<0.05), but indexes of rash and tachycardia
      were worse. The two methods of sedation were comparable for nausea, vomiting,
      desaturation, agitation and laryngospasm (P>0.05). CONCLUSIONS: Based on the
      current evidence, the group receiving atropine had reduced hypersalivation and
      increased rash and tachycardia; no differences were observed in nausea, vomiting,
      desaturation, agitation and laryngospasm between the two groups. Given that some
      of the studies were of low quality, additional high-quality randomized controlled
      trials should be conducted to further verify these findings.

PMID- 29656946
TI  - Impact of rapid response car system on ECMO in out-of-hospital cardiac arrest.

PMID- 29656947
TI  - Effectiveness of interventions to improve the efficiency of emergency department
      operations: An evidence map.

PMID- 29656948
TI  - Management update of potentially premalignant oral epithelial lesions.
AB  - The term oral potentially malignant disorders, proposed at the World Health
      Organization workshop in 2005, has now been renamed potentially premalignant oral
      epithelial lesions (PPOELs). It is important to differentiate among PPOELs, which
      is a broad term to define a wide variety of clinical lesions, and oral epithelial
      dysplasia, which should be reserved specifically for lesions with biopsy-proven
      foci of dysplasia. PPOELs encompass lesions that include leukoplakia,
      erythroplakia, erythroleukoplakia, lichen planus, and oral submucous fibrosis.
      The primary goal of management of dysplasia includes prevention, early detection,
      and treatment before malignant transformation. The aim of this article is to
      inform the clinician about management of PPOELs.

PMID- 29656949
TI  - Beginning the CAR T cell therapy revolution in the US and EU.

PMID- 29656950
TI  - The Elicitation of Relaxation and Interoceptive Awareness Using Floatation
      Therapy in Individuals With High Anxiety Sensitivity.
AB  - BACKGROUND: Floatation-REST (Reduced Environmental Stimulation Therapy), an
      intervention that attenuates exteroceptive sensory input to the nervous system,
      has recently been found to reduce state anxiety across a diverse clinical sample
      with high levels of anxiety sensitivity (AS). To further examine this anxiolytic
      effect, the present study investigated the affective and physiological changes
      induced by Floatation-REST and assessed whether individuals with high AS
      experienced any alterations in their awareness for interoceptive sensation while
      immersed in an environment lacking exteroceptive sensation. METHODS: Using a
      within-subject crossover design, 31 participants with high AS were randomly
      assigned to undergo a 90-minute session of Floatation-REST or an exteroceptive
      comparison condition. Measures of self-reported affect and interoceptive
      awareness were collected before and after each session, and blood pressure was
      measured during each session. RESULTS: Relative to the comparison condition,
      Floatation-REST generated a significant anxiolytic effect characterized by
      reductions in state anxiety and muscle tension and increases in feelings of
      relaxation and serenity (p < .001 for all variables). Significant blood pressure
      reductions were evident throughout the float session and reached the lowest point
      during the diastole phase (average reduction >12 mm Hg). The float environment
      also significantly enhanced awareness and attention for cardiorespiratory
      sensations. CONCLUSIONS: Floatation-REST induced a state of relaxation and
      heightened interoceptive awareness in a clinical sample with high AS. The
      paradoxical nature of the anxiolytic effect in this sample is discussed in
      relation to Wolpe's theory of reciprocal inhibition and the regulation of
      distress via sustained attention to present moment visceral sensations such as
      the breath.

PMID- 29656952
TI  - [To the question of elective induction of labor at 39 weeks of gestation, the
      answer lies in the question].
AB  - The goal of induction of labor is to achieve vaginal delivery when the benefits
      of expeditious delivery outweigh the risks of continuing the pregnancy. In order
      to correctly understand the problematic of the elective induction of labor at 39
      weeks of gestation (WG), two questions must be raised. (i) What is the perinatal
      mortality evolution according the gestational age at delivery? All the most
      recent and methodologically well-conducted studies are convergent: they show that
      the fetal mortality risk exceeds the perinatal/infant (during the first year of
      life) mortality risk from 39 WG. The benefit/risk balance related to the
      expectant management is therefore reversed from 39 WG in favor of the elective
      induction of labor when the considered issue is the perinatal mortality. (ii)
      What are the associated risks with elective induction of labor? While some
      observational studies suggested that the elective induction of labor after 37 WG
      was associated with an increased risk of cesarean sections, these studies
      presented a major methodological bias: an error in the control group selection.
      Indeed, the control group consisted of women in spontaneous labor, whereas the
      appropriate comparison group must be an expectant management group. Several large
      cohort studies using a rigorous methodology have shown that elective induction of
      labor at 39 WG reduces the cesarean section risk compared to an expectant
      management. Three systematic reviews with meta-analysis of randomized controlled
      trials comparing induction of labor with expectant management were published: two
      showed that the cesarean section risk was lowered with the induction of labor
      compared to an expectant management and the third that the cesarean section rates
      were similar. Finally, the most recent randomized controlled trial, published in
      2016, showed no significant difference between the 2 arms in the cesarean section
      rate. In all, the most recent literature data, free from comparative bias, show
      that elective induction of labor at term is associated with a significant
      reduction in the cesarean section risk and perinatal morbidity and mortality
      compared to an expectant management.

PMID- 29656953
TI  - [Cesarean after labor induction: Risk factors and prediction score].
AB  - OBJECTIVES: The objective of the study is to determine the risk factors for
      caesarean section at the time of labor induction, to establish a prediction
      algorithm, to evaluate its relevance and to compare the results with observation.
      METHODS: A retrospective study was carried out over a year at Nantes University
      Hospital with 941 cervical ripening and labor inductions (24.1%) terminated by
      167 caesarean sections (17.8%). Within the cohort, a case-control study was
      conducted with 147 caesarean sections and 148 vaginal deliveries. A multivariate
      analysis was carried out with a logistic regression allowing the elaboration of
      an equation of prediction and an ROC curve and the confrontation between the
      prediction and the reality. RESULTS: In univariate analysis, six variables were
      significant: nulliparity, small size of the mother, history of scarried uterus,
      use of prostaglandins as a mode of induction, unfavorable Bishop score<6, variety
      of posterior release. In multivariate analysis, five variables were significant:
      nulliparity, maternal size, maternal BMI, scar uterus and Bishop score. The most
      predictive model corresponded to an area under the curve of 0.86 (0.82-0.90) with
      a correct prediction percentage ("well classified") of 67.6% for a caesarean
      section risk of 80%. CONCLUSION: The prediction criteria would make it possible
      to inform the woman and the couple about the potential risk of Caesarean section
      in urgency or to favor a planned Caesarean section or a low-lying attempt on more
      objective, repeatable and transposable arguments in a medical team.

PMID- 29656954
TI  - Medical device innovation and the value analysis process.
AB  - Heidi A. Krantz, RN, BSN is the Director of Value Analysis at Johns Hopkins
      Bayview Medical Center in the Johns Hopkins Health System. Barbara Strain, MA,
      CVAHP is the Director of Value Management at the University of Virginia Health
      System. Jane Torzewski RN, MAN, MBA is a Senior Category Manager for the Mayo
      Clinic Physician Preference Contracting team. She previously was a Senior
      Clinical Value Analyst on the Mayo Clinic Value Analysis team.

PMID- 29656951
TI  - Auditory System Target Engagement During Plasticity-Based Interventions in
      Schizophrenia: A Focus on Modulation of N-Methyl-D-Aspartate-Type Glutamate
      Receptor Function.
AB  - Cognitive deficits are predictive of long-term social and occupational functional
      deficits in schizophrenia but are currently without gold-standard treatments. In
      particular, augmentation of auditory cortical neuroplasticity may represent a
      rate-limiting first step before addressing higher-order cognitive deficits. We
      review the rationale for N-methyl-d-aspartate-type glutamate receptor (NMDAR)
      modulators as treatments for auditory plasticity deficits in schizophrenia, along
      with potential serum and electroencephalographic target engagement biomarkers for
      NMDAR function. Several recently published NMDAR-modulating treatment studies are
      covered, involving D-serine, memantine, and transcranial direct current
      stimulation. While all three interventions appear to modulate auditory
      plasticity, direct agonists (D-serine) appear to have the largest and most
      consistent effects on plasticity, at least acutely. We hypothesize that there may
      be synergistic effects of combining procognitive NMDAR-modulating approaches with
      auditory cortical neuroplasticity cognitive training interventions. Future
      studies should assess biomarkers for target engagement and patient
      stratification, along with head-to-head studies comparing putative interventions
      and potential long-term versus acute effects.

PMID- 29656955
TI  - From innovation to market adoption in the operating room: The "CFO as customer".
AB  - Dr Egeland is senior director of business development and licensing in the Early
      Technologies business unit of the Minimally Invasive Therapies Group at
      Medtronic. Mr Rapp is an associate consultant at Pharmagellan, a biotech
      consultancy. Dr David is the founder and managing director of Pharmagellan.

PMID- 29656956
TI  - Ultrasound-assessed visceral fat and associations with glucose homeostasis and
      cardiovascular risk in clinical practice.
AB  - BACKGROUND AND AIMS: Despite the lack of evidence that assessing the global
      cardiovascular risk leads to a decreased incidence of cardiovascular events,
      accurate patient profiling is paramount in preventive medicine. An excess of
      visceral fat (VF) is associated with an enhanced cardiovascular risk;
      importantly, VF is quantifiable rapidly, cheaply and safely by ultrasound, which
      makes it suitable for use in clinical practice. In the present study, we aimed to
      evaluate if US-measured VF (USVF) could be a better predictor of glucose
      homeostasis and cardiovascular risk than simple anthropometric measures. METHODS
      AND RESULTS: One-hundred sixty-two patients attending a Metabolic Disorders
      Clinic underwent a cross-sectional study for which USVF, anthropometric measures,
      a standard oral glucose tolerance test (OGTT), and calculation of cardiovascular
      Framingham score and vascular age were obtained. USVF was directly correlated
      with fasting and 2-h plasma glucose (respectively: r = 0.26, p < 0.001; r = 0.28,
      p < 0.0001), fasting and 2-h plasma insulin (for both: r = 0.41, p < 0.0001),
      homeostatic model assessment of insulin resistance (HOMA-IR; r = 0.42, p <
      0.0001), cardiovascular Framingham score (r = 0.44 p < 0.0001) and vascular age
      (r = 0.30 p < 0.001). In receiver operator characteristic curves USVF had good
      diagnostic abilities for type 2 diabetes mellitus, fatty liver and metabolic
      syndrome, in both genders. At multivariate analysis, body mass index (BMI)
      outperformed USVF in the prediction of HOMA-IR; neverthless, USVF, not BMI, was
      an independent predictor of cardiovascular risk. Finally, models including USVF
      were the most parssimonious to predict Framingham score, vascular age and HOMA
      IR. CONCLUSION: In overweight and obese subjects, USVF could usefully complement
      other parameters for cardiovascular risk stratification.

PMID- 29656957
TI  - Muramyl dipeptide potentiates a Bacillus anthracis poly-gamma-d-glutamic acid
      capsule surrogate that induces maturation and activation of mouse dendritic
      cells.
AB  - Poly-gamma-d-glutamic acid (PGA) of anthrax is an important pathogenic factor due
      to its anti-phagocytic activity. Additionally, PGA has the ability to activate
      mouse macrophages for the secretion of cytokines through Toll-like receptor (TLR)
      2. Peptidoglycan (PGN), a major bacterial cell-wall component, induces
      inflammatory responses in the host. We assessed whether PGA can induce maturation
      and cytokine expression in immature mouse dendritic cells (DCs) in the existence
      of muramyl dipeptide (MDP), the minimum motif of PGN with immunostimulatory
      activity. Stimulation of immature DCs with PGA or MDP alone augmented expression
      of costimulatory molecules and MHC class II proteins, which are all cell surface
      markers indicative of maturation. The observed effects were further enhanced by
      costimulation of PGA and MDP. PGA alone was sufficient to induce expression of
      TNF-alpha, IL-6, MCP-1, and MIP1-alpha, whereas MDP alone did not under the same
      conditions. Treatment with MDP enhanced PGA-induced expression of the tested
      inflammatory mediators; however, the synergistic effect found for PGA and MDP was
      not observed in TLR2- or nucleotide-binding oligomerization domain (NOD) 2
      knockout DCs. Additionally, MDP augmented PGA-induced MAP kinases and NF-kappaB
      activation, which is crucial for expression of cytokines. Furthermore, MAP kinase
      and NF-kappaB inhibitors attenuated MDP enhancement of PGA-induced cytokine
      production. In addition, co-culture of splenocytes and PGA/MDP-matured DCs
      induced higher expression of IL-2 and IFN-gamma compared to that of splenocytes
      and PGA-matured DCs. Collectively, our results suggest that PGA and MDP
      cooperatively induce inflammatory responses in mouse DCs through TLR2 and NOD2
      via MAP kinase and NF-kappaB pathways, subsequently leading to lymphocyte
      activation.

PMID- 29656958
TI  - Polymorphisms in TLRs influence circulating cytokines production in Plasmodium
      vivax malaria: TLR polymorphisms influence cytokine productions in malaria-vivax.
AB  - The efficiency of the immune system has been shaped throughout the evolutionary
      process allowing adaptations. In a Plasmodium vivax infection, the host attempts
      to develop an innate immune response to keep in check the parasite that is
      associated with inflammatory and regulatory processes. Production of pro
      inflammatory and regulatory cytokines simultaneously appears to be a balancing
      mechanism for the host to prevent the onset of severe disease. Changes in the
      dynamics of circulating cytokines production can influence the pathogenesis,
      severity of the disease and episodes of recurrent Plasmodium vivax malaria (Pv
      malaria). A cross-sectional study was conducted in endemic areas for Pv-malaria
      in the Amazonas State, Brazil. Several SNPs in TLR genes were genotyped by PCR
      RFLP in 137 patients infected with P. vivax. Circulating cytokines IL-6, TNF, IL
      2, IL-10, IFN-gamma and IL-4 were measured by CBA. Influence of the studied SNPs
      on circulating cytokines was investigated by applying the Kruskal-Wallis test
      followed by Dunns' multiple comparison post-test. A Spearman correlation test
      also was performed to elaborate circulating cytokine networks and to demonstrate
      the level of interaction between each molecule. Individuals with genotypes A/G
      (TLR4 A299G), C/C (TLR6 S249P) and T/T (TLR9 -1486C/T) appear to produce
      less/gain IL-6, IFN-gamma, IL-10, IL-2 and IL-4 compared to patients with wild
      type and heterozygous genotypes. In addition, these genotypes seem to influence
      the interaction network between the molecules studied, causing a lower
      interaction, absence or even negative interaction between the cytokines. Data
      presented in this study suggests the influence of polymorphisms TLR4 (A299G),
      TLR6 (S249P) and TLR9 (-1486C/T) on the production of circulating cytokines
      during Pv-malaria.

PMID- 29656959
TI  - Genetic variants in IL-33/ST2 pathway with the susceptibility to hepatocellular
      carcinoma in a Chinese population.
AB  - Interleukin (IL)-33/ST2 pathway plays a pivotal role in tumorigenesis through
      influencing cancer stemness, tumor growth, metastasis, angiogenesis, and
      accumulation of regulatory T cells in tumor microenvironments. The aim of this
      study was to investigate the association of IL-33 rs7025417 and ST2 rs3821204
      with the risk of hepatocellular carcinoma (HCC). Genotyping of IL-33 rs7025417
      and ST2 rs3821204 was carried out using a Taqman assay. IL-33 and ST2 mRNA was
      examined using real-time PCR and plasma IL-33 and sST2 levels were measured using
      enzyme-linked immunosorbent assay. The ST2 rs3821204 CC genotype was associated
      with a significantly increased risk of HCC (CC vs. GG: adjusted OR = 2.29, 95%
      CI, 1.39-3.78; dominant model: adjusted OR = 1.58, 95% CI, 1.12-2.23; recessive
      model: adjusted OR = 1.88, 95% CI, 1.21-2.93; C vs. G: adjusted OR = 1.53, 95%
      CI, 1.20-1.95). Gene-environment interaction analysis showed that the risk effect
      of rs3821204 CG/CC genotypes was more evident in smokers (adjusted OR = 1.70, 95%
      CI, 1.13-2.55) and drinkers (adjusted OR = 1.57, 95% CI, 1.04-2.37). The
      increased risk was also observed in combined analysis. Moreover, HCC patients
      with ST2 rs3821204 CC genotype had higher levels of mRNA and protein expression
      (P < 0.05). These findings suggest that ST2 rs3821204 CC genotype may contribute
      to hepatocarcinogenesis by enhancing ST2 production at the transcriptional and
      translational level.

PMID- 29656960
TI  - Circulating Vascular Basement Membrane Fragments are Associated with the Diameter
      of the Abdominal Aorta and Their Expression Pattern is Altered in AAA Tissue.
AB  - OBJECTIVE: Abdominal aortic aneurysm (AAA) is characterised by enhanced
      proteolytic activity, and extracellular matrix (ECM) remodelling in the vascular
      wall. Type IV and XVIII collagen/endostatin are structural proteins in vascular
      basement membrane (VBM), a specialised ECM structure. Here the association
      between plasma levels of these collagens with the aortic diameter and expansion
      rate is studied, and their expression in aortic tissue characterised. METHODS:
      This was a retrospective population based cohort study. Type IV and XVIII
      collagen/endostatin were analysed in plasma by ELISA assay in 615 men, divided
      into three groups based on the aortic diameter: 1) normal aorta <= 25 mm, 2) sub
      aneurysmal aorta (SAA) 26-29 mm, and 3) AAA >= 30 mm. Follow up data were
      available for 159 men. The association between collagen levels and aortic
      diameter at baseline, and with the expansion rate at follow up were analysed in
      ordinal logistic regression and linear regression models, controlling for common
      confounding factors. Tissue expression of the collagens was analysed in normal
      aorta (n = 6) and AAA (n = 6) by immunofluorescence. RESULTS: Plasma levels of
      type XVIII collagen/endostatin (136 ng/mL [SD 29] in individuals with a normal
      aorta diameter, 154 ng/ml [SD 45] in SAA, and 162 ng/ml [SD 46] in AAA; p = .001)
      and type IV collagen (105 ng/mL [SD 42] normal aorta, 124 ng/ml [SD 46] SAA, and
      127 ng/ml [SD 47] AAA; p = .037) were associated with a larger aortic diameter. A
      significant association was found between the baseline levels of type
      XVIII/endostatin and the aortic expansion rate (p = .035), but in the
      multivariable model, only the initial aortic diameter remained significantly
      associated with expansion (p = .005). Altered expression patterns of both
      collagens were observed in AAA tissue. CONCLUSION: Plasma levels of circulating
      type IV and XVIII collagen/endostatin increase with AAA diameter. The expression
      pattern of VBM proteins is altered in the aneurysm wall.

PMID- 29656961
TI  - In-hospital outcomes of percutaneous ventricular assist devices versus intra
      aortic balloon pumps in non-ischemia related cardiogenic shock.
AB  - INTRODUCTION: This study compared inpatient outcomes related to the use of these
      two devices among patients who developed cardiogenic shock not due to acute
      myocardial infarction or coronary revascularization. METHODS: We extracted
      admission-level records of patients with a diagnosis of cardiogenic shock who
      underwent either PVAD or IABP implantation from the National Inpatient Sample
      (NIS) database from 2010 to 2014. Our outcomes of interest were mortality and
      length of stay. RESULTS: Inpatient mortality was significantly higher in the PVAD
      cohort. In multivariate analysis, PVAD use in these patients was associated with
      higher mortality. There was no difference in the length of stay between both
      groups among patients that survived to discharge. CONCLUSION: In our analysis of
      the NIS database, the use of PVADs in patients with cardiogenic shock of non
      ischemic origin was associated with higher mortality when compared to IABP use.

PMID- 29656962
TI  - Treatment of platelet concentrates and plasma with riboflavin and UV light:
      Impact in bacterial reduction.
AB  - OBJECTIVES: Transfusion of hemocomponents is essential for clinical and surgical
      procedures and therefore their safety has increased. An option for pathogen
      reduction includes the combination of riboflavin and UV light. To our knowledge,
      there are no studies in Latin America that demonstrate the effectiveness of the
      pathogen reduction in hemocomponents. The objective of this work was to evaluate
      the efficiency of a pathogens reduction system in platelets concentrates (PC) and
      plasma. MATERIALS AND METHODS: PC and plasma were contaminated with Escherichia
      coli, Klebsiella pneumoniae, Streptococcus pyogenes and Staphylococcus
      epidermidis at 104 to 106 CFU and subjected to bacterial reduction. After
      bacterial reduction, hemocomponents were subjected to cultivation of surviving
      bacteria by automated method and classical colonies quantification. Additionally,
      quality control testing was performed in order to confirm the integrity of
      platelets and coagulation laboratory values in plasma before and after bacterial
      reduction. RESULTS: The bacterial death in PC/plasma was expressed by Logarithmic
      Reduction Value as follows: for both strains (E. coli and S. pyogenes) 4/4, 5/5
      and 6/6; for K. pneumoniae 2.54/2.23, 2.94/2.22 and 3.44/2.98, for S. epidermidis
      4/4, 3.11/5 and 3.23/4.19, for 104, 105 and 106 CFU, respectively. In PC and
      plasma, platelet count, pH (at 22 degrees C), activated partial thromboplastin
      time (aPTT), prothrombin time (PT), fibrinogen, factor VIII and total proteins
      (TP) were slightly modified. CONCLUSIONS: UV light with riboflavin is able to
      reduce an important number of pathogens in hemocomponents; however, the bacterial
      reduction is influenced by the nature and quantity of the pathogen.

PMID- 29656963
TI  - Rapid Discharge in Total Hip Arthroplasty: Utility of the Outpatient Arthroplasty
      Risk Assessment Tool in Predicting Same-Day and Next-Day Discharge.
AB  - BACKGROUND: Hospital length of stay is a major driver of cost in the total hip
      arthroplasty (THA) episode of care, and as a result, significant efforts are
      being made to minimize it. This study aims to assess the utility of the
      Outpatient Arthroplasty Risk Assessment (OARA) screening tool in accurately
      identifying patients for safe and early discharge after THA. METHODS: A
      retrospective review was conducted on 332 consecutive patients who underwent
      primary THA at a single tertiary academic center. Patients were evaluated using
      the OARA score, a tool that has been proposed to identify patients who can safely
      undergo early discharge after THA. The validity of these claims was assessed by
      analyzing the OARA score's positive and negative predictive values for high vs
      low OARA scores between patients enrolled in our (1) same-day discharge (SDD) and
      2) next-day discharge (NDD) pathways. RESULTS: When comparing the utility of the
      OARA score in accurately predicting length of stay, the OARA score demonstrated a
      (1) higher, but constant, positive predictive value for discharge on
      postoperative day (POD) 0 for SDD (86.1%) than POD1 for NDD (35.5%) and (2) lower
      negative predictive value for discharge on POD0 (23.1%) for SDD than POD1 for NDD
      (86.1%). CONCLUSION: The OARA score was developed to risk-stratify patients who
      can safely undergo SDD or NDD after THA. In this study, the OARA score was a
      highly predictive tool in identifying NDD patients at risk for failure of
      discharge by POD1.

PMID- 29656964
TI  - Artificial Intelligence, Machine Learning, Deep Learning, and Cognitive
      Computing: What Do These Terms Mean and How Will They Impact Health Care?
AB  - This article was presented at the 2017 annual meeting of the American Association
      of Hip and Knee Surgeons to introduce the members gathered as the audience to the
      concepts behind artificial intelligence (AI) and the applications that AI can
      have in the world of health care today. We discuss the origin of AI, progress to
      machine learning, and then discuss how the limits of machine learning lead data
      scientists to develop artificial neural networks and deep learning algorithms
      through biomimicry. We will place all these technologies in the context of
      practical clinical examples and show how AI can act as a tool to support and
      amplify human cognitive functions for physicians delivering care to increasingly
      complex patients. The aim of this article is to provide the reader with a basic
      understanding of the fundamentals of AI. Its purpose is to demystify this
      technology for practicing surgeons so they can better understand how and where to
      apply it.

PMID- 29656965
TI  - Total Hip Arthroplasty for Periacetabular Metastatic Disease. An Original
      Technique of Reconstruction According to the Harrington Classification.
AB  - BACKGROUND: Periacetabular metastatic disease requires complex acetabular
      reconstruction. The complication rate for these frail patients is high. Various
      cement-rebar reinforced techniques allowing cemented total hip arthroplasty (THA)
      have been described. The optimal procedure has not yet been identified. METHODS:
      A continuous series of 131 THAs performed in 126 patients with periacetabular
      metastatic disease was prospectively included in this study. After bone
      metastasis curettage and cementation, an original technique of acetabular
      reconstruction was performed using a dual mobility cup cemented into an
      acetabular reinforcement device (ie, Kerboull cross-plate or Burch-Schneider
      antiprotrusio cage) according to the Harrington classification. Functional
      outcome for independent ambulation in the community, pain relief, and occurrence
      of dislocation or mechanical failure of the acetabular reconstruction were
      assessed. RESULTS: At a mean follow-up of 33 +/- 17 months, the improvement in
      the preoperative to postoperative functional outcome and pain relief was
      significant (P < .001). The dislocation rate was 2%. Two of the 3 cases of
      dislocation occurred in acetabular reconstructions associated with a proximal
      femoral arthroplasty. No mechanical failure or aseptic loosening of the
      acetabular reconstruction was observed. CONCLUSION: This study emphasized that
      our original technique combining bone metastasis curettage and cementation,
      acetabular reinforcement device and cemented dual mobility cup was effective to
      restore a painless functional independence and ensure a durable acetabular
      reconstruction able to face to adjuvant radiation therapy and mechanical
      solicitations for long survivors. In addition, dual mobility cup limited the risk
      of dislocation in patients undergoing THA for periacetabular metastatic disease.

PMID- 29656966
TI  - Corrigendum to 'Modular Neck vs Nonmodular Femoral Stems in Total Hip
      Arthroplasty - Clinical Outcome, Metal Ion Levels, and Radiologic Findings'
      [Journal of Arthroplasty 32 (2017) 2774-2778].

PMID- 29656968
TI  - Anatomical Features of the Descending Genicular Artery to Facilitate Surgical
      Exposure for the Subvastus Approach-A Cadaveric Study.
AB  - BACKGROUND: The purpose of this cadaveric study was to clarify the proximal limit
      for the subvastus approach (SVA) in total knee arthroplasty to decrease potential
      vascular injury. METHODS: Seventy embalmed knees underwent a modified SVA using a
      14-cm oblique medial incision. Anatomical features of the descending genicular
      artery (DGA) were investigated with regard to variation, distance of the vessels
      from surgical landmarks, and sex differences. RESULTS: The DGA was identified in
      62 knees (89%), while it was absent in 8 knees (11%); in the latter, the
      articular, saphenous, and muscular branches arose separately from the femoral
      artery. The mean distances from the tibial tuberosity and medial joint line to
      the origin of the DGA were 15.5 +/- 1.6 cm and 12.6 +/- 1.6 cm, respectively.
      Both distances were significantly longer in males than in females (P < .01,
      respectively). A strong positive correlation was found between the distance from
      the tibial tuberosity to the origin of the DGA and the distance from the medial
      joint line to the origin of the DGA (Spearman's correlation coefficient, R2 =
      0.72, P < .01). A weak positive correlation was found between the distance from
      the tibial tuberosity to the origin of the DGA and lower leg length (R2 = 0.13, P
      < .01). No vascular injuries were observed in this surgical exposure. CONCLUSION:
      The DGA showed several variations and was absent 11% of the time. An oblique
      medial incision within 14 cm from the tibial tuberosity followed by arthrotomy is
      considered a safe zone for the SVA.

PMID- 29656967
TI  - Conversion vs Primary Total Hip Arthroplasty: Increased Cost of Care and
      Perioperative Complications.
AB  - BACKGROUND: With the increasing incidence of hip fractures and hip preservation
      surgeries, there has been a concomitant rise in the number of conversion total
      hip arthroplasties (THAs) performed. Prior studies have shown higher complication
      rates in conversion THA. However, there is a paucity of data showing differences
      in cost between these 2 procedures. Currently, the Center for Medicare and
      Medicaid Services bundles primary and conversion THA in the same Medicare
      Severity-Diagnosis Related Group for hospital reimbursement. More evidence is
      needed to support the reclassification of conversion THA. METHODS: The cohort
      provided by the institutional database included 163 conversion THAs between
      January 1, 2012 and December 31, 2015. Intraoperative complications, estimated
      blood loss, operative time, postoperative complications, and perioperative cost
      data were analyzed for 163 primary THA patients matched to the conversion THA
      cohort. RESULTS: Compared with primary THA, conversion THA had significantly (P <
      .05) greater cost for direct labor, other direct costs, intermediate nursing
      services, other diagnostic/therapy, surgery services,
      physical/occupational/speech therapy, radiology, laboratories, blood,
      medical/surgical supply, and total direct costs. In addition, the conversion THA
      group had significantly greater operative times, estimated blood loss, length of
      stay, intraoperative complications, and postoperative complications. CONCLUSION:
      Conversion THA, as compared with primary THA, is associated with greater costs
      (approximately 19% greater), increased surgical times, and perioperative
      complications. To prevent these additional expenses from creating patient
      selection bias and a barrier to care, the conversion THA Medicare Severity
      Diagnosis Related Group should be reclassified, or modifiers created.

PMID- 29656969
TI  - The Leukocyte Esterase Test Strip Is a Poor Rule-Out Test for Periprosthetic
      Joint Infection.
AB  - BACKGROUND: The urinary leukocyte esterase (LE) test strip has been suggested as
      a good screening test for periprosthetic joint infection (PJI). The purpose of
      this study is to compare the diagnostic profile of LE assays from different
      manufacturers and determine whether the LE test strip is a good rule-out test.
      METHODS: Synovial fluid samples (N = 344), sent to 1 laboratory for PJI testing,
      were used in this prospective study. Four different tests for synovial fluid LE
      were simultaneously evaluated for their performance in detecting white blood cell
      (WBC) positive samples (>3000 cells/uL). RESULTS: Both neutrophil elastase
      immunoassays demonstrated greater sensitivity than urinary LE test strips (92.0%
      and 90.8% vs 72.4% and 80.3%; all P < 0.011). Fifty-three percent of false
      negative urinary LE test strip results clearly missed the presence of elevated
      levels of synovial fluid LE. Invalid urinary LE test strip results were 4-fold
      more likely among WBC (+) compared with WBC (-) samples (27.0% vs 6.8%; P <
      0.0001). The combined failure to detect an elevated WBC count, because of either
      false-negative or invalid results, was 47.1% and 41.4% for the Roche and Siemens
      test strips, respectively. CONCLUSIONS: This study agrees with the existing
      literature demonstrating that the LE test strips are among the lowest sensitivity
      tests for PJI. The urinary LE tests strips should not be used to rule-out PJI, as
      they often fail to detect abundant levels of LE in synovial fluid. Instead, it is
      more appropriate to use the (++) LE test strip result as a secondary confirmatory
      rule-in test for PJI because of its high specificity.

PMID- 29656970
TI  - Predictability of Pelvic Tilt During Total Hip Arthroplasty Using a Traction
      Table.
AB  - BACKGROUND: Pelvic positioning during total hip arthroplasty (THA) affects
      functional position of the acetabular component. We sought to evaluate whether
      preoperative pelvic tilt correlated with intraoperative pelvic tilt while
      positioned on a traction table for direct anterior THA and furthermore to
      evaluate whether there was a consistent and predictable effect on pelvic tilt
      while positioned for surgery. METHODS: We evaluated the sagittal spinopelvic
      preoperative standing and supine pelvic tilt radiographic measurements as
      compared with intraoperative measurements of 25 patients. Changes in pelvic tilt
      were analyzed for statistical significance and interobserver reliability.
      RESULTS: The mean standing pelvic tilt was 13.5 degrees  +/- 5.7 degrees . The
      mean supine pelvic tilt was 13.3 degrees  +/- 6.1 degrees . There was no
      statistically significant difference between standing and supine pelvic tilt (P =
      .866). The mean intraoperative pelvic tilt was 3.0 degrees  +/- 6.2 degrees .
      There was a statistically significant decrease in pelvic tilt between both
      standing to intraoperative comparison and supine to intraoperative comparison (P
      < .0001 for both). Difference in mean between these comparisons was 10.5 degrees 
      +/- 4.6 degrees  (95% confidence interval, 8.7 degrees -12.3 degrees ) and 10.3
      degrees  +/- 6.3 degrees  (95% confidence interval, 7.8 degrees -12.8 degrees ),
      respectively. CONCLUSION: Patient positioning on a traction table for direct
      anterior THA has a reliable effect on pelvic tilt in the magnitude of
      approximately 10 degrees  decreased pelvic tilt. This effect on pelvic tilt
      correlates to approximately 7.4 degrees  and 3 degrees  altered anteversion and
      inclination, respectively. Taking into account this change in pelvic tilt at the
      time of surgery will allow the hip arthroplasty surgeon to more accurately place
      acetabular components in the desired functional position.

PMID- 29656971
TI  - Long-Term Outcomes After Metal-on-Metal Total Hip Arthroplasty With a 28-mm Head:
      A 17- to 23-Year Follow-Up Study of a Previous Report.
AB  - BACKGROUND: Second-generation, metal-on-metal total hip arthroplasty (MoM THA)
      using a 28-mm head has shown favorable results compared with large head MoM THA.
      The purpose of this study is to evaluate the long-term outcomes of cementless
      primary MoM THA with a 28-mm head and the incidence of osteolysis using computed
      tomography. METHODS: A total of 92 patients (53 men and 39 women) who underwent
      primary cementless MoM THA (114 hips) with a 28-mm head were enrolled in this
      study. Their mean age was 46.2 years at the time of surgery. The mean follow-up
      duration was 20 years. The Harris hip score, presence of thigh or groin pain,
      radiographic results, presence of peri-implant osteolysis, histologic analysis,
      and Kaplan-Meier survival curves were evaluated. RESULTS: The mean preoperative
      Harris hip score of 50.5 improved to 85.1 at the final follow-up. Eight patients
      (8 hips) experienced groin pain, but none had thigh pain. Twelve revisions (6.2%)
      were performed including 10 hips for aseptic loosening with osteolysis and 2 hips
      for periprosthetic fracture around the stem. At 23 years, 91% of patients were
      free from revision of the acetabular component due to aseptic loosening and 90.1%
      were free from revision of both femoral and acetabular components due to any
      reason. Osteolysis was identified around the cup in 12 cases (10.5%) and around
      the stem in 7 cases (6.1%). CONCLUSION: MoM THA with a 28-mm head showed a
      relatively low rate of aseptic implant loosening at a mean follow-up of 20 years.

PMID- 29656972
TI  - Clinical Outcomes of Gap Balancing vs Measured Resection in Total Knee
      Arthroplasty: A Systematic Review and Meta-Analysis Involving 2259 Subjects.
AB  - BACKGROUND: The argument on the clinical effects between gap balancing (GB) and
      measured resection (MR) in total knee arthroplasty remains to be resolved. A
      systematic review and meta-analysis was performed to investigate which technique
      in total knee arthroplasty has better clinical effect. METHODS: A total of 20
      studies involving 2259 cases were included in the meta-analysis. The primary
      outcome measure was Knee Society Score (KSS), whereas the secondary outcomes
      included other function assessment systems (eg, range of motion, Western Ontario
      and McMaster University Osteoarthritis Index), radiological outcomes (eg, femoral
      component rotation, total outliers), revision rate, complications (eg, infection,
      loosening, instability), and surgical time. RESULTS: The GB technique was
      associated with statistically significant increases in the primary outcomes of
      KSS-function in 1 year. However, a mean difference of 2.12 points was below the
      minimal clinically important difference of 6 points. No differences were found in
      the analyses of KSS-knee and KSS-function in any other follow-up periods.
      Secondary outcome assessments showed significant decreased surgical time (mean
      difference, 16.18; P < .00001) for MR. Although statistically significant
      difference in favor of GB was identified in total outliers (risk ratio, 1.72, P =
      .0004), the 2 techniques were comparable in range of motion, Western Ontario and
      McMaster University Osteoarthritis Index, femoral component rotation,
      complications, and revision rate. CONCLUSION: We conclude that both techniques
      can result in equivalent results when done properly, and each surgeon must
      understand the strengths and weaknesses of each technique.

PMID- 29656973
TI  - How Fast Should a Total Knee Arthroplasty Be Performed? An Analysis of 140,199
      Surgeries.
AB  - BACKGROUND: Although previous studies have shown that prolonged operative times
      can lead to an increased risk of complications after total knee arthroplasty
      (TKA), they only evaluated a few complications. It is also unclear whether a
      distinctive operative time exists after which complications increase. Therefore,
      this study was performed to (1) assess whether higher operative time increases
      the risk of complications within 30 days of TKA and (2) explore the relationship
      between operative time and various complications to identify possible operative
      times where complication rates increase. METHODS: The National Surgical Quality
      Improvement Project database was queried from 2011 to 2015 to identify 140,199
      primary TKAs. The effect of operative time (skin-to-skin) on various medical and
      surgical complications within 30 days was evaluated using multivariable logistic
      regression models. Spline regression models were created to further study the
      relationship between operative time and complications. RESULTS: After adjusting
      for confounding factors, longer operative times were associated with higher risks
      of readmission (P < .001), reoperation (P < .001), surgical site infection (P <
      .001), wound dehiscence (P < .001), and transfusion (P < .001). The majority of
      the complications demonstrated an increase throughout the range of operative
      time, with a slightly pronounced increase in the risk of complications when the
      operative time was longer than 80 minutes. CONCLUSION: Prolonged operative times
      were associated with an increased risk of a number of important complications
      such as readmissions, reoperations, surgical site infections, and wound
      complications. Based on our results, an operative time goal of less than 80
      minutes is helpful for minimizing these complications after TKA.

PMID- 29656974
TI  - Low-Dose Aspirin Is Safe and Effective for Venous Thromboembolism Prophylaxis
      Following Total Knee Arthroplasty.
AB  - BACKGROUND: Aspirin is an effective prophylaxis for venous thromboembolism (VTE)
      after total knee arthroplasty (TKA). The optimal prophylactic aspirin dose has
      not been established. The study aims to compare 2 aspirin regimens with regard to
      the incidence of (1) symptomatic deep venous thrombosis (DVT), (2) pulmonary
      embolism (PE), (3) bleeding, and (4) mortality within 90 days after TKA. METHODS:
      We retrospectively identified 5666 patients who received aspirin twice daily for
      4 to 6 weeks after TKA. A total of 1327 patients received 81-mg BID and 4339
      patients received 325-mg BID aspirin. Postoperative complications collected were
      VTEs (DVT and PE), bleeding (gastrointestinal or wound bleeding), and mortality.
      RESULTS: The incidence of VTE was 1.5% in the 325-mg group and 0.7% in the 81-mg
      group (P = .02). Symptomatic DVT was 1.4% in the 325-mg aspirin compared with
      0.3% for the 81-mg aspirin (P = .0009). Regression model showed no correlation
      between aspirin dose and VTE incidence (odds ratio [OR] = 1.03; 95% confidence
      interval [95% CI], 0.45-2.36; P = .94) or DVT (OR = 0.50; 95% CI, 0.16-1.55; P =
      .20). The incidence of PE was 0.2% in the high-aspirin group compared with 0.4%
      in the low-aspirin group (P = .13). Bleeding was 0.2% in the 325-mg aspirin group
      and 0.2% in the 81-mg aspirin group (P = .62), and 90-day mortality was similar
      (0.1%) between the groups (P = .56). CONCLUSION: Low-dose aspirin was not
      inferior to high-dose aspirin for the prevention of VTE after TKA. Low-dose
      aspirin can be considered a safe and effective agent in the prevention of VTE
      after TKA.

PMID- 29656975
TI  - Response to Letter to the Editor on "Local Infiltration Analgesia With Liposomal
      Bupivacaine Improves Pain Scores and Reduces Opioid Use After Total Knee
      Arthroplasty: Results of a Randomized Controlled Trial".

PMID- 29656976
TI  - The Influence of Postoperative Knee Stability on Patient Satisfaction in Cruciate
      Retaining Total Knee Arthroplasty.
AB  - BACKGROUND: Although knee stability is well known as an important element for the
      success of total knee arthroplasty (TKA), the direct relationship between
      clinical outcomes and knee stability is still unknown. The purpose of this study
      was to determine if postoperative knee stability and soft-tissue balance affect
      the functional outcomes and patient satisfaction after cruciate-retaining (CR)
      TKA. METHODS: Fifty-five patients with varus osteoarthritis of the knee who
      underwent CR TKA were included in this study, and their postoperative knee
      stability was assessed by stress radiography at extension and flexion 1 month
      postoperatively. Timed Up and Go test, patient-derived clinical scores using the
      2011 Knee Society Score, and Forgotten Joint Score-12 were also assessed at 1
      year postoperatively. The effects of stability parameters on clinical outcomes
      were analyzed using Spearman's rank correlation. RESULTS: Medial stability at
      both knee extension and flexion had significant correlations with the shorter
      Timed Up and Go test and the higher patient satisfaction. Moreover, lateral
      laxity at extension was significantly correlated with the better patient
      satisfaction and Forgotten Joint Score-12. However, these correlation
      coefficients in this study were low in the range of 0.32-0.51. CONCLUSION: Medial
      stability and lateral laxity play an important role in influencing 1-year
      postoperative clinical outcomes after CR TKA. However, we should keep in mind
      that these correlations are weak with coefficients at 0.50 or less and the
      clinical results are also affected by various other factors.

PMID- 29656977
TI  - Liposomal Bupivacaine vs Plain Bupivacaine in Periarticular Injection for Control
      of Pain and Early Motion in Total Knee Arthroplasty: A Randomized, Prospective
      Study.
AB  - BACKGROUND: The use of multimodal pain regimens has been shown to be an effective
      technique for the treatment of postoperative pain after total knee arthroplasty.
      Periarticular injections, of both short-acting and long-acting anesthetics, have
      emerged as an additional method of providing significant improvement in
      postoperative pain relief. The purpose of this study is to compare the efficacy
      of periarticular injection using long-acting vs short-acting preparations.
      METHODS: A randomized, prospective study of 80 consecutive patients was performed
      comparing liposomal bupivacaine vs plain bupivacaine periarticular injection. The
      primary outcomes included pain relief, total narcotic usage, and completion of
      physical therapy goals, specifically range of motion. RESULTS: No significant
      improvements were noted between liposomal bupivacaine and plain bupivacaine
      injection groups in overall pain reduction, range of motion, or total narcotic
      usage. At 24 hours, small statistically significant differences in physical
      therapy pain scores were noted with liposomal bupivacaine vs plain bupivacaine
      and control patients, but these differences did not persist at later time points.
      Both preparations demonstrated statistically significant improvements in range of
      motion when compared to historical controls, but no differences were noted
      between preparations. CONCLUSION: Overall, minimal significant differences were
      noted between liposomal bupivacaine and plain bupivacaine at early and late time
      points. Both preparations of periarticular injection demonstrated superiority
      over control pain regimens but were relatively equivalent to one another in
      direct comparison.

PMID- 29656978
TI  - High Rate of Early Revision After Custom-Made Unicondylar Knee Arthroplasty.
AB  - BACKGROUND: There has been a recent interest in custom-made partial knee
      arthroplasties to provide patient-specific instrumentation and better fit of the
      prosthesis. While unicondylar knee arthroplasties (UKAs) have demonstrated good
      outcomes and durable results in many studies, there is little evidence on
      outcomes of these custom-made implants. METHODS: We performed a retrospective
      review of all custom-made UKAs performed at our institution by one surgeon from
      2008 to 2015. We analyzed preoperative demographics, clinical follow-up
      evaluations, and radiographs and performed an analysis of risk factors including
      age, gender, height, weight, body mass index, and tibial insert thickness. The
      incidence of revision surgery, radiographic failures indicating component
      loosening, and symptomatic clinically failed implants was calculated at an
      average of 54.0 months of follow-up. RESULTS: We analyzed 115 consecutive custom
      made medial UKAs from a single surgeon at our institution and found 29 (25.2%)
      UKAs had failed at an average of 33.1 months after surgery. Reasons for failure
      included aseptic femoral loosening (10), aseptic tibial loosening (8), loosening
      of both components (4), infection (3), progression of osteoarthritis (2), pain
      (1), and dislodged polyethylene insert (1). We found a significant relationship
      between implant failure and body mass index; no other study variables were
      statistically significant. CONCLUSION: We found a relatively high rate of aseptic
      loosening and particularly femoral component loosening in the short- to
      intermediate-term follow-up period. While further study of larger numbers of
      custom-made UKA from multiple institutions may help verify these findings, we
      recommend careful consideration of the use of this implant.

PMID- 29656979
TI  - Reducing Length of Stay Does Not Increase Emergency Room Visits or Readmissions
      in Patients Undergoing Primary Hip and Knee Arthroplasties.
AB  - BACKGROUND: Total hip and total knee arthroplasty (total joint arthroplasty
      [TJA]) are 2 of the most common elective surgeries. Identifying which patients
      are at highest risk for emergency room (ER) visits or readmissions within 90 days
      of surgery and the reasons for return are crucial to formulate ways to decrease
      these visits and improve patient outcomes. METHODS: This is a retrospective
      review of a consecutive series of 7466 unilateral primary TJA performed from July
      2013 to June 2017; any patients who had an ER visit or readmission in the first
      90 days after surgery were identified, and a detailed chart review was performed.
      Patients discharged home or to rehab were analyzed separately. RESULTS: Three
      hundred thirty-six (4.5%) patients had 380 ER visits and 250 (3.3%) patients had
      291 readmissions in the first 90 days after TJA. Patients returning to the ER
      were equivalent to those who did not. Patients who went to a rehab facility on
      discharge were significantly more likely to be readmitted (P = .000). Patients
      who were readmitted had a higher American Society of Anesthesiologists score (P =
      .000). Length of stay decreased over the study period from 2.66 days to 1.63
      days, while the number of unplanned interventions remained steady. Pain and
      swelling was the most common reason for return for ER visits (33.2%) and
      readmissions (14.1%). CONCLUSION: The overall number of unplanned interventions
      after TJA in this population was low and remained consistent over time despite
      decreasing length of stay. Patients who went to rehab were more likely to
      experience readmission. The majority of unplanned interventions occurred in the
      first 4 weeks after surgery.

PMID- 29656980
TI  - The Recovery Curve for the Patient-Reported Outcomes Measurement Information
      System Patient-Reported Physical Function and Pain Interference Computerized
      Adaptive Tests After Primary Total Knee Arthroplasty.
AB  - BACKGROUND: We sought to characterize the typical recovery in physical function
      (PF) and pain interference (PI) after TKA using Patient-Reported Outcomes
      Measurement Information System (PROMIS) patient-reported outcome (PRO) measures.
      METHODS: Ninety-one patients were enrolled into an institutional review board 
      approved prospective observational study. PROs were obtained preoperatively and
      postoperatively at 6 weeks, 3 months, 6 months, and 1 year. PROs included the
      PROMIS PF computerized adaptive test (CAT) and the PROMIS PI CAT. Generalized
      estimating equations were used to evaluate outcomes over time. RESULTS: There was
      no difference in the preoperative and 6-week postoperative T-scores for the PF
      CAT (P = .410). However, all subsequent postoperative T-scores were greater than
      the preoperative T-score (all, P < 0.05). There was a significant reduction in PI
      CAT T-scores between the preoperative and all subsequent postoperative T-scores
      (all, P < .05). A clinically important difference in PF CAT T-scores (beta =
      5.44, 95% confidence interval 4.10-6.80; P < .001) and PI CAT T-scores (beta = 
      7.46, 95% confidence interval -9.52 to -5.40; P < 0.001) was seen between the
      preoperative and 3-month postoperative visits. Sixty-three percent of the
      improvement in PF occurred by 3 months, and 89% had occurred by 6 months. The
      majority of reduction in PI (68%) occurred by 3 months and 90% had occurred by 6
      months. CONCLUSION: The greatest magnitude of improvement in both PF and PI
      occurred within the first 3 months. After 6 months, patients might expect modest
      improvements in PF and mild reductions of PI. Patients and surgeons should use
      this information for setting expectations, planning for recovery, and improving
      care.

PMID- 29656981
TI  - Dual-Agent Antibiotic Prophylaxis Using a Single Preoperative Vancomycin Dose
      Effectively Reduces Prosthetic Joint Infection Rates With Minimal Renal Toxicity
      Risk.
AB  - BACKGROUND: We performed this study to compare prosthetic joint infection (PJI)
      and renal toxicity rates following hip and knee total joint arthroplasty (TJA)
      when a first-generation cephalosporin was administered either alone or in
      combination with a single preoperative vancomycin dose, whether vancomycin
      administration timing potentially influenced dual-antibiotic PJI prophylaxis
      approach effectiveness, and whether single-dose vancomycin use increased risk of
      renal impairment. METHODS: This was a retrospective study of 1997 consecutive
      primary TJAs (1871 patients) treated with cefazolin alone (1044 TJAs) or
      cefazolin with single-dose vancomycin (953 TJAs). The vancomycin group included
      476 TJAs (450 patients) with infusion started at least 45 minutes before the skin
      incision and 477 TJAs (464 patients) with infusion started less than 45 minutes
      before the skin incision. RESULTS: The addition of a single dose of vancomycin
      did not significantly reduce PJI rates when compared with cefazolin alone (1.6%
      vs 2.1%, P = .32). However, the PJI rate was significantly lower following
      primary TJA when vancomycin administration was initiated at least 45 minutes
      before incision (0.2%) when compared with other TJA procedures performed using
      cefazolin and vancomycin (2.9%, P < .01) or cefazolin alone (2.1%, P < .01). We
      observed no difference in renal toxicity between treatment groups. CONCLUSION: In
      our institution, the addition of vancomycin to cefazolin at least 45 minutes
      before incision reduced PJI infection rates in primary hip and knee TJA with a
      low risk of renal impairment.

PMID- 29656982
TI  - Erratum to "Whole brain neuronal abnormalities in focal epilepsy quantified with
      proton MR spectroscopy" [Epilepsy Res. 139 (2018) 85-91].

PMID- 29656983
TI  - Prophylaxis and treatment of foetal growth restriction.
AB  - Foetal growth restriction (FGR) and associated placental pathologies such as pre
      eclampsia and stillbirth arise in early pregnancy when inadequate remodelling of
      maternal spiral arteries leads to persistent high-resistance low-flow
      uteroplacental circulation. Current interventions concentrate on targeting the
      placental ischaemia-reperfusion injury and oxidative stress associated with an
      imbalance in angiogenic/anti-angiogenic factors. Recent meta-analyses confirm
      that aspirin modestly reduces the risk for small-for-gestational-age pregnancy in
      high-risk women. A dose of >=100 mg starting by 16 weeks of gestation is
      recommended. In vitro and in vivo studies suggest that low-molecular-weight
      heparin may prevent FGR; further research is needed to confirm efficacy. Once FGR
      is diagnosed, no treatment will improve foetal growth. Potential FGR therapies
      such as phosphodiesterase type-5 inhibitors or maternal VEGF gene therapy aim to
      improve poor placentation and/or uterine blood flow. Melatonin, creatine and N
      acetyl cysteine have potential as novel neuroprotective and cardioprotective
      agents in FGR.

PMID- 29656984
TI  - Corrigendum to "Benign and malignant pathology of the uterus" [Best Pract Res
      Clin Obstet Gynaecol 46 (2018) 12-30].

PMID- 29656985
TI  - In silico analysis of the potential mechanism of telocinobufagin on breast cancer
      MCF-7 cells.
AB  - BACKGROUNDS AND AIMS: The extractives from a ChanSu, traditional Chinese
      medicine, have been discovered to possess anti-inflammatory and tumor-suppressing
      abilities. However, the molecular mechanism of telocinobufagin, a compound
      extracted from ChanSu, on breast cancer cells has not been clarified. The aim of
      this study is to investigate the underlying mechanism of telocinobufagin on
      breast cancer cells. METHODS AND MATERIALS: The differentially expressed genes
      after telocinobufagin treatment on breast cancer cells were searched and
      downloaded from Gene Expression Omnibus (GEO), ArrayExpress and literatures.
      Bioinformatics tools were applied to further explore the potential mechanism of
      telocinobufagin in breast cancer using the Kyoto Encyclopedia of genes and
      genomes (KEGG) pathway, Gene ontology (GO) enrichment, panther, and protein
      protein interaction analyses. To better comprehend the role of telocinobufagin in
      breast cancer, we also queried the Connectivity Map using the gene expression
      profiles of telocinobufagin treatment. RESULTS: One GEO accession (GSE85871)
      provided 1251 differentially expressed genes after telocinobufagin treatment on
      MCF-7 cells. The pathway of neuroactive ligand-receptor interaction, cell
      adhesion molecules (CAMs), intestinal immune network for IgA production,
      hematopoietic cell lineage and calcium signaling pathway were the key pathways
      from KEGG analysis. IGF1 and KSR1, owning to higher protein levels in breast
      cancer tissues, IGF1 and KSR1 could be the hub genes related to telocinobufagin
      treatment. It was indicated that the molecular mechanism of telocinobufagin
      resembled that of fenspiride. CONCLUSIONS: Telocinobufagin might regulate
      neuroactive ligand-receptor interaction pathway to exert its influences in breast
      cancer MCF-7 cells, and its molecular mechanism might share some similarities
      with fenspiride. This study only presented a comprehensive picture of the role of
      telocinobufagin in breast cancer MCF-7 cells using big data. However, more
      thorough and deeper researches are required to add to the validity of this study.

PMID- 29656986
TI  - Eight-and-a-Half Syndrome: A Combination of Intracranial Capillary Telangiectasia
      and Hematencephalon.
AB  - Eight-and-a-half syndrome, a combination of one-and-a-half syndrome and
      ipsilateral facial palsy, was first described by Eggenberger in 1998.
      Intracranial capillary telangiectasia (ICT) is a rare type of latent cerebral
      vascular malformation characterized by a number of small, dilated, and thin
      walled blood capillaries with normal brain tissues between them. Susceptibility
      weighted imaging is the recommended diagnostic method to detect ICT. Oommen once
      reported 1 case about pontine hemorrhage causing Fisher one-and-a-half syndrome
      with facial paralysis. Here, we report a case with regard to pontine tegmentum
      ICT and hematencephalon presenting as eight-and-a-half syndrome.

PMID- 29656987
TI  - Differential Prognostic Impact on Mortality of Myocardial Infarction Compared
      With Bleeding Severity in Contemporary Acute Coronary Syndrome Patients.
AB  - INTRODUCTION AND OBJECTIVES: The impact on mortality of myocardial infarction
      (MI) compared with the specific degree of bleeding severity occurring after
      discharge in acute coronary syndrome is poorly characterized. Defining this
      relationship may help to achieve a favorable therapeutic risk-benefit balance.
      METHODS: Using Cox-based shared frailty models, we assessed the relationship
      between mortality and postdischarge MI and bleeding severity-graded according to
      Bleeding Academic Research Consortium (BARC)-in 4229 acute coronary syndrome
      patients undergoing in-hospital coronary arteriography between January 2012 and
      December 2015. RESULTS: Both MI (HR, 5.8; 95%CI, 3.7-9.8) and bleeding (HR, 5.1;
      95%CI, 3.6-7.7) were associated with mortality. Myocardial infarction had a
      stronger impact on mortality than BARC type 2 and 3a bleedings: (RRr, 3.8 and
      1.9; P < .05), respectively, but was equivalent to BARC type 3b (RRr, 0.9; P =
      .88). Mortality risk after MI was significantly lower than after BARC type 3c
      bleeding (RRr, 0.25; P < .001). Mortality was higher after an MI in patients on
      dual antiplatelet therapy (DAPT) at the time of the event (HR, 2.9; 95%CI, 1.8
      4.5) than in those off-DAPT (HR, 1.5; 95%CI, 0.7-3.4). In contrast, mortality was
      lower after a bleeding event in patients on-DAPT (HR, 1.6; 95%CI, 1.1-2.6) than
      in those off-DAPT (HR, 3.2; 95%CI, 1.7-5.8). CONCLUSIONS: The differential effect
      on mortality of a postdischarge MI vs bleeding largely depends on bleeding
      severity. The DAPT status at the time of MI or bleeding is a modifier of
      subsequent mortality risk.

PMID- 29656988
TI  - Cationic nucleopeptides as novel non-covalent carriers for the delivery of
      peptide nucleic acid (PNA) and RNA oligomers.
AB  - Cationic nucleopeptides belong to a family of synthetic oligomers composed by
      amino acids and nucleobases. Their capability to recognize nucleic acid targets
      and to cross cellular membranes provided the basis for considering them as novel
      non-covalent delivery agents for nucleic acid pharmaceuticals. Herein, starting
      from a 12-mer nucleopeptide model, the number of cationic residues was modulated
      in order to obtain new nucleopeptides endowed with high solubility in acqueous
      medium, acceptable bio-stability, low cytotoxicity and good capability to bind
      nucleic acid. Two candidates were selected to further investigate their potential
      as nucleic acid carriers, showing higher efficiency to deliver PNA in comparison
      with RNA. Noteworthy, this study encourages the development of nucleopeptides as
      new carriers to extend the known strategies for those nucleic acid analogues,
      especially PNA, that still remain difficult to drive into the cells.

PMID- 29656989
TI  - Substituent effect of N-benzylated gramine derivatives that prevent the PP2A
      inhibition and dissipate the neuronal Ca2+ overload, as a multitarget strategy
      for the treatment of Alzheimer's disease.
AB  - Following the premises of the multitarget-directed ligands approach for the drug
      R&D against neurodegenerative diseases, where Alzheimer's disease (AD) outstands,
      we have synthesized and evaluated analogues of the gramine derivative ITH12657 (1
      benzyl-5-methyl-3-(piperidin-1-ylmethyl-1H-indole, 2), which had shown important
      neuroprotective properties, such as blocking effect of voltage-gated Ca2+
      channels (VGCC), and prevention of phosphoprotein phosphatase 2A (PP2A)
      inhibition. The new analogues present different substitutions at the pending
      phenyl ring, what slightly modified their pharmacological characteristics. The
      VGCC blockade was enhanced in derivatives possessing nitro groups, while the pro
      PP2A feature was ameliorated by the presence of fluorine. Chlorine atoms supplied
      good activities over the two biological targets aimed; nevertheless that
      substitution provoked loss of viability at 100-fold higher concentrations (10
      MUM), what discards them for a deeper pharmacological study. Overall, the para
      fluorine derivative of ITH12657 was the most promising candidate for further
      preclinical assays.

PMID- 29656991
TI  - Model predicting the ypN0 status after good response to chemoradiotherapy in
      rectal cancer.
AB  - BACKGROUND: The purpose of this study was to identify the predictive factors for
      ypN0 status in tumors with good pathologic response to chemoradiotherapy (CRT).
      METHODS: A retrospective chart review was conducted on patients at two tertiary
      cancer center who underwent rectal resection after good response to CRT between
      2000 and 2013. RESULTS: No preoperative treatment (oxaliplatin use, radiotherapy
      boost of 5,4 Gy, delay CRT-surgery) impacted on the ypN status. In the
      multivariate analysis, only a ypT<3 (HR 7.5 [2,9-19.5]) was significant and no
      lymphovascular invasion (HR 8,9 [1.6-49.8]) was limited to significance.The best
      model predicting the ypN0 status used only the ypT status<3. The major part
      (92.2%) of patients with ypT0-2 tumors had no LN invasion. CONCLUSION: The risk
      of lymph node involvement metastases was only 7.8% for the patients with an ypT0
      2 status. A fullthickness transanal resection coud be the futur treatment of
      these patients.

PMID- 29656990
TI  - Synthesis and antiproliferative activity of derivatives of the phyllanthusmin
      class of arylnaphthalene lignan lactones.
AB  - A series of arylnaphthalene lignan lactones based on the structure of the
      phyllanthusmins, a class of potent natural products possessing diphyllin as the
      aglycone, has been synthesized and screened for activity against multiple cancer
      cell lines. SAR exploration was performed on both the carbohydrate and lactone
      moieties of this structural class. These studies have revealed the importance of
      functionalization of the carbohydrate hydroxy groups with both acetylated and
      methylated analogues showing increased potency relative to those with
      unsubstituted sugar moieties. In addition, the requirement for the presence and
      position of the C-ring lactone has been demonstrated through reduction and
      selective re-oxidation of the lactone ring. The most potent compound in this
      study displayed an IC50 value of 18 nM in an HT-29 assay with several others
      ranging from 50 to 200 nM. In an effort to elucidate their potential mechanism(s)
      of action, the DNA topoisomerase IIa inhibitory activity of the most potent
      compounds was examined based on previous reports of structurally similar
      compounds, but does not appear to contribute significantly to their
      antiproliferative effects.

PMID- 29656992
TI  - Cryptosporidium species in post-weaned and adult sheep and goats from N.W. Spain:
      Public and animal health significance.
AB  - Application of molecular approaches has led to a significant progress on the
      knowledge of the epidemiology of Cryptosporidium spp. Nevertheless, molecular
      information on the occurrence of cryptosporidiosis in domestic small ruminants,
      especially in goats, are limited and restricted to the study of a modest number
      of isolates, mainly from diarrhoeic neonates. In order to determine the
      Cryptosporidium species present in healthy post-weaned and adult small ruminants
      from north-western Spain and to analyse a possible age-related distribution of
      species, faecal specimens were collected in sheep and goat farms without neonatal
      diarrhoea outbreaks the year before the sampling. Cryptosporidium spp. DNA was
      detected by SSU-rRNA PCR-RFLP, using restriction enzymes SspI, VspI and MboII. C.
      parvum and C. ubiquitum isolates were further characterized at the GP60 locus.
      Our results reveal that Cryptosporidium spp. is widely distributed in small
      ruminant farms (47.4-50.0%), although its prevalence is low in both hosts (5.9
      6.0%). No significant differences in individual prevalence were detected between
      age groups. C. xiaoi and the zoonotic C. parvum and C. ubiquitum were identified.
      In sheep, C. parvum was the predominant species and its prevalence increased with
      age, in contrast to C. xiaoi; C. ubiquitum was an occasional finding in adults.
      In goats, C. xiaoi and C. ubiquitum were the most frequent species and slightly
      more prevalent in adults than in post-weaned kids, in contrast to C. parvum.
      Subtyping analysis of C. parvum isolates revealed the presence of IIaA15G2R1 and
      IIaA14G2R1 in sheep, whereas IIaA13G1R1 and IIdA17G1 were restricted to goats;
      only the C. ubiquitum XIIa subtype 3 was found. Although the prevalences detected
      are low, these values are probably underestimated due to, amongst others, the
      cross-sectional design of the study and the intermittent oocyst-excretion of post
      weaned and adult small ruminants. Thus, these animals may play an important role
      in the appearance of cryptosporidiosis outbreaks in humans and domestic ruminant
      neonates and therefore should be considered as a potential threat to animal
      production and human health.

PMID- 29656993
TI  - Anthelmintic resistance in goat herds-In vivo versus in vitro detection methods.
AB  - Anthelmintic resistance (AR) is a serious threat to animal health and has a major
      economic impact worldwide due to production and financial losses. The aim of this
      study was to determine the occurrence of AR on 30 goat farms in Slovakia during
      the pasturing seasons and to compare three widely used in vitro and in vivo
      methods for detecting AR in field conditions. A three-year survey was conducted
      during the pasturing seasons of 2014-2016. Goats on each farm were split into
      treated and control groups and were treated by recommended (5 mg/kg body weight)
      and double doses (10 mg/kg b.w.) of albendazole. Comparisons between percent
      reduction in a faecal egg count reduction test (FECRT) and an egg hatch test
      (EHT) and the presence of L3 larvae in a larval development test (LDT) using
      resistant concentrations of benzimidazole (BZ) were monitored after treatment.
      The FECRT indicated percent reductions of 69.2-86.2% for the single dose and of
      36.3-45.4% for the double dose. The EHT indicated that all farms had BZ-resistant
      nematodes. Low (<15% hatching) and high (>15% hatching) levels of resistance were
      detected on 13 and 17 farms, respectively. The LDT failed to detect resistant
      larvae on seven farms but detected low and high levels of resistance on seven and
      14 farms, respectively. The data indicate a moderate correlation between in vitro
      and in vivo tests for detecting BZ resistance among the 30 goat farms. The
      hatching detected by the EHT and the presence of L3 larvae by the LDT at
      resistant BZ concentrations provided reasonable identification of low levels of
      resistance in the parasite populations, but the use of a double dose for a
      treatment may underestimate the real occurrence of low levels of resistant
      parasites on goat farms.

PMID- 29656994
TI  - An ex vivo abomasal ovine model to study the immediate immune response in the
      context of Haemonchus contortus larval-stage.
AB  - We have set up an ex vivo ovine abomasal model, which can mimic the multicellular
      process to explore the early steps in haemonchine nematode infection using RNA
      seq technology. Ovine abomasal explants were collected for histological and
      transcriptional analysis and supernatants collected to quantitate lactate
      dehydrogenase (LDH) enzymes. Atotal of 233 were substantially induced genes
      between L4-inoculated and uninoculated-control tissues, respectively. However, a
      total of 14 were considerably down-regulated genes between the 51 aforementioned
      tissues. Fifteen pathways were annotated by Kyoto Encyclopedia of Genes, and
      Genomes pathway analysis accounted for the significant percentage in immediate
      response to larval-stage of H. contortus. Key genes upregulated in response to
      the addition of L4-inoculum of H. contortus were IL-6, IL-8, C1q, Atypical
      chemokine receptor-3, chemokine ligand-2, manganese superoxide dismutase,
      integrin alpha-7, -8, -9, integrin subunit beta-1, integrin subunit beta 6,
      intercellular adhesion molecule-1 and actin alpha-1. This study shows for the
      first time that galectin-1 is up-regulated in an ex vivo abomasal segment model
      exposed to L4-inoculum of H. contortus following 6 h of incubation. The abomasal
      segment model has been shown to be a suitable tool to study the haemonchine
      larval-stage effects on the ovine abomasal tissues prior to in vivo assessment.

PMID- 29656995
TI  - First detection of Trichinella pseudospiralis infection in raccoon (Procyon
      lotor) in Central Europe.
AB  - The raccoon (Procyon lotor) is a North American carnivore introduced to Europe in
      the 20th Century. Raccoons are believed to be the potential hosts of many
      parasites, or to be involved in their transmission to other animals. Nematodes of
      the genus Trichinella can infect many carnivorous and omnivorous animals
      worldwide. The aim of the present study was to determine the occurrence of
      Trichinella spp. infection in raccoons in Central Europe. Muscle samples were
      collected from various regions of Poland, the Czech Republic and Germany during
      the years 2012-2016. The larvae of Trichinella spp. were detected in 11 raccoons,
      and these were identified as T. spiralis and T. pseudospiralis by multiplex PCR
      (89.9% and 9.1%, respectively). No mixed infection was observed. This is the
      first report describing the occurrence of T. spiralis and T. pseudospiralis in P.
      lotor in Central Europe. Our findings also show that the raccoon population acts
      as a reservoir of Trichinella pseudospiralis.

PMID- 29656997
TI  - Veterinary parasitology teaching at London - Meeting the 'Day-One Competency'
      needs of new veterinarians.
AB  - Over the past four decades, there has been an exponential increase in veterinary
      parasitology knowledge, coinciding with the advent of molecular biology in
      research. Therefore, it is unrealistic for teachers to expect students to
      graduate with an encyclopaedic knowledge of the subject. As a result, a new
      curriculum was introduced at The Royal Veterinary College (University of London)
      in 2007, designed to meet the needs of our new graduates, i.e. RCVS Day-One
      Competences. The aims of this curriculum are, inter alia, to ensure that new
      graduates have an up-to-date body of core knowledge and are able to apply such
      knowledge and newly-acquired information to scientific and clinical problem
      solving. Veterinary parasitology is taught primarily in Year 2, following a brief
      introduction in Year 1; clinical aspects are covered in Year 3, with original
      research projects undertaken in Years 4 and 5. Parasitology is taught in parallel
      with other subjects, enabling both horizontal and vertical integration. Core
      material is provided in lectures supplemented by directed learning (DL) in small
      groups and interactive, clinical scenario-based practical classes. Student
      learning is supported by Moodle 3.2 (Virtual Learning Environment [VLE], RVC
      Learn) which provides access to an on-line study guide (annotated using Adobe
      Reader), PowerPoint presentations with synchronized lecturer commentary (Echo
      Active Learning Platform [ALP]), detailed feedback for DL and practical classes,
      parasite 'potcasts' and CAL packages, and a Clinical Skills Centre. A
      parasitology textbook has also been published recently to support courses taught
      at the College. Assessment of student learning is achieved using a variety of
      written formats (essay, problem-solving questions [PSQ], multiple choice
      questions [MCQ] and extended matching questions [EMQ]), integrated oral
      examinations and objective structured clinical examinations (OSCEs).

PMID- 29656996
TI  - Prevalence of Angiostrongylus vasorum, Aelurostrongylus abstrusus and Crenosoma
      vulpis larvae in native slug populations in Germany.
AB  - Metastrongyloid parasites represent sparsely studied parasites of dogs and cats
      in Germany. Recent European surveys indicate that these parasites are spreading
      in Europe. Actual data on prevalence of Angiostrongylus vasorum in dogs and foxes
      reveal several endemic foci in Germany. However, actual data on the prevalence of
      A. vasorum and other metastrongyloid lungworm larvae in a wide range of slug and
      snail intermediate hosts, such as Arion lusitanicus, are missing for Germany. To
      fill this gap, we conducted an epidemiological survey on native German slugs in
      selected regions of Hesse and Rhineland-Palatinate. The focus was on slugs,
      because in study areas slugs appear to be more abundant than snails. Slugs were
      collected throughout different seasons of the year in areas that were previously
      proven to be hyperendemic for A. vasorum fox infections. Overall, a total of 2701
      slugs were collected and examined for lungworm larvae via artificial digestion.
      The number of A. vasorum larvae per slug varied considerably (1-546 larvae per
      specimen). Some hotspot areas with high A. vasorum prevalence in slugs (up to
      19.4%) were identified. The overall A. vasorum prevalence varied with season with
      largest number of slugs infected in summer (9.1%) and lowest number in winter
      (0.8%). The current study revealed a total A. vasorum prevalence of 4.7% in slugs
      based on microscopic analyses. Confirmation of lungworm species was made by
      specific duplex-real-time PCRs. Hence, these data demonstrate that final hosts
      are at a permanent risk for A. vasorum infections during all seasons when living
      in investigated areas. Besides A. vasorum, other lungworm larvae were also
      detected, such as Crenosoma vulpis (the fox lungworm, 2.3%) and Aelurostrongylus
      abstrusus (feline lungworm, 0.2%).

PMID- 29656998
TI  - Changes in the concentration of anti-Leishmania antibodies in saliva of dogs with
      clinical leishmaniosis after short-term treatment.
AB  - The aim of this study was to evaluate the possible changes in the concentration
      of anti-Leishmania antibodies in saliva samples from dogs with clinical
      leishmaniosis after short-term treatment. Twenty dogs with clinical signs and
      laboratory abnormalities compatible with canine leishmaniosis (CanL) were
      diagnosed and treated with a standard antimonial plus allopurinol therapy. The
      concentration of anti-Leishmania IgG2 and IgA antibodies in saliva was measured
      at the time of diagnosis (day 0) and after treatment (day 30) by time-resolved
      immunofluorometric assays (TR-IFMAs) and results were compared with those of
      serum. In addition, correlations between antibody concentrations in saliva and
      serum, clinical scores and selected laboratory analytes were calculated. TR-IFMA
      results were expressed as Units of Fluorometry for Leishmania (UFL). Most dogs
      that adequately responded to treatment (n = 17) showed a reduction of anti
      Leishmania antibodies in saliva [median IgG2: from 678.0 (day 0) to 201.1 UFL
      (day 30), p < 0.0001; median IgA: from 91.3 (day 0) to 60.2 UFL (day 30), p <
      0.01] in accordance with clinical improvement (p < 0.0001). However, two of these
      dogs showed an increase of anti-Leishmania antibodies in saliva. Among dogs that
      did not improve after one month of treatment (n = 3), two showed a reduction in
      serum and saliva antibodies. In these two dogs, clinical recovery was achieved
      after one additional month of treatment with allopurinol. The other dog that did
      not respond to treatment showed increases in the concentration of anti-Leishmania
      antibodies, both in saliva and serum, and did not adequately respond to an
      additional month of treatment with allopurinol. From this pilot study, it could
      be concluded that, despite the low number of dogs used, the measurement of anti
      Leishmania IgG2 and IgA antibodies in saliva could have a potential use for
      treatment monitoring of CanL, provided that a sufficient amount of specific
      antibodies is present at diagnosis. This is because, especially in the case of
      IgG2, there is a high correlation between the saliva and serum concentrations,
      and the reduction of antibodies is generally in accordance with the clinical
      improvement. Further long-term studies with a larger population should be
      undertaken to confirm this potential.

PMID- 29656999
TI  - Estimating prevalence and diagnostic test characteristics of bovine cysticercosis
      in Belgium in the absence of a 'gold standard' reference test using a Bayesian
      approach.
AB  - A Bayesian model was developed to estimate values for the prevalence and
      diagnostic test characteristics of bovine cysticercosis (Taenia saginata) by
      combining results of four imperfect tests. Samples of 612 bovine carcases that
      were found negative for cysticercosis during routine meat inspection collected at
      three Belgian slaughterhouses, underwent enhanced meat inspection (additional
      incisions in the heart), dissection of the predilection sites, B158/B60 Ag-ELISA
      and ES Ab-ELISA. This Bayesian approach allows for the combination of prior
      expert opinion with experimental data to estimate the true prevalence of bovine
      cysticercosis in the absence of a gold standard test. A first model (based on a
      multinomial distribution and including all possible interactions between the
      individual tests) required estimation of 31 parameters, while only allowing for
      15 parameters to be estimated. Including prior expert information about
      specificity and sensitivity resulted in an optimal model with a reduction of the
      number of parameters to be estimated to 8. The estimated bovine cysticercosis
      prevalence was 33.9% (95% credibility interval: 27.7-44.4%), while apparent
      prevalence based on meat inspection is only 0.23%. The test performances were
      estimated as follows (sensitivity (Se) - specificity (Sp)): enhanced meat
      inspection (Se 2.87% - Sp 100%), dissection of predilection sites (Se 69.8% - Sp
      100%), Ag-ELISA (Se 26.9% - Sp 99.4%), Ab-ELISA (Se 13.8% - Sp 92.9%).

PMID- 29657000
TI  - Activity of the extract of Acmella oleracea on immature stages of Amblyomma
      sculptum (Acari: Ixodidae).
AB  - This study evaluated the acaricidal activity of the methanol extract of Acmella
      oleracea with 0.187% of spilanthol against immature stages of Amblyomma sculptum.
      The packet test was used to evaluate the extract's activity on unengorged larvae
      and nymphs, testing concentrations of 0.4 to 50 mg/mL for larvae and 12.5 to
      200.0 mg/mL for nymphs. For the engorged stages, the immersion test was used, at
      concentrations of 0.4 to 50 mg/mL for larvae and 12.5 to 200.0 mg/mL for nymphs.
      The methanol extract caused 100% mortality of the unengorged larvae and nymphs
      starting at concentrations of 12.5 and 200.0 mg/mL, respectively. For engorged
      larvae and nymphs, the mortality was 100% starting from concentrations of 12.5
      and 150.0 mg/mL, respectively. The LC50 for unengorged larvae was 3.2 mg/mL,
      while for engorged larvae it was 6.6 mg/mL. For unengorged nymphs, the LC50 was
      38.5 mg/mL, but it was not possible to calculate the corresponding value for
      engorged nymphs because the data did not fit the probit model. These results
      demonstrate that the methanol extract of A. oleracea has acaricidal activity
      against different immature stages of A. sculptum.

PMID- 29657001
TI  - Accuracy of a diagnostic model based on serum biochemical parameters in detecting
      cows at an increased risk of chronic fascioliasis.
AB  - In adult cattle Fasciola hepatica infection usually follows a chronic subclinical
      course, and reduces both the milk yield and milk quality, resulting in
      considerable financial losses. Effective control of the disease is based on
      reliable identification of asymptomatically infected individuals, which now
      requires special parasitological or serological diagnostic tests. It is also
      known that F. hepatica infection induces alterations in some serum biochemical
      parameters. Therefore, the study was conducted to develop a model based on serum
      biochemical parameters allowing to identify cows at higher risk of chronic
      fascioliasis. Six hundred sixty eight adult dairy cows from 97 herds located in
      central and northeastern Poland were clinically examined, and blood and fecal
      samples from them were collected for a routine monitoring of fascioliasis and
      metabolic profile. Using the combination of fecal sedimentation test and indirect
      ELISA based on excretory/secretory products 203 cows, apparently healthy in
      clinical examination, were definitively classed as affected by (47 cows, 23.2%)
      or free from (156 cows, 76.8%) chronic fascioliasis. Their serum was screened for
      the activity of 4 enzymes (gamma-glutamyl transpeptidase, glutamate
      dehydrogenase, aspartate aminotransferase, creatine kinase) and concentration of
      18 other components (total bilirubin, total protein, albumin, globulin, urea,
      glucose, non-esterified fatty acids, beta-hydroxybutyrate, sodium, potassium,
      chloride, calcium, magnesium, copper, zinc, iron, selenium, and haptoglobin).
      Logistic regression analysis was used to build 4 multivariable models allowing
      for identification of cows at risk of chronic fascioliasis. Then, the accuracy
      was compared between the models using the area under the receiver operating
      characteristic curve (AUROC), and an optimal cut-off value was determined for the
      most accurate model using Youden J index. The most accurate proved to be the
      model based on glutamate dehydrogenase activity and globulin, urea (all three
      positively linked with risk of chronic fascioliasis), and selenium concentration
      (negatively linked) adjusted by the access to pasture and cow's age. At the
      optimal cut-off of 0.37 this model had sensitivity of 85.1% (CI 95%:72.3%,
      92.6%), specificity of 90.4% (CI 95%:84.7%, 94.1%), positive likelihood ratio of
      8.8 (CI 95%:5.4, 14.5), and negative likelihood ratio of 0.16 (CI 95%:0.08,
      0.33). This model performed significantly better than model including only gamma
      glutamyl transpeptidase or model including both gamma-glutamyl transpeptidase and
      aspartate aminotransferase (both also adjusted by the access to pasture and cow's
      age), and was the only model which performed significantly better than the basic
      model based solely on the access to pasture and cow's age.

PMID- 29657002
TI  - Clinical management of canine leishmaniosis versus human leishmaniasis due to
      Leishmania infantum: Putting "One Health" principles into practice.
AB  - The initiative One World, "One Health" tries to rapidly detect emerging or
      reemerging human and animal infectious diseases and prevent epidemiological
      situations such as deforestation, some agricultural practices or the appearance
      of new foci of leishmaniosis due to Leishmania infantum with alternative
      reservoirs. With this objective in mind, we here consider leishmaniosis in the
      Mediterranean basin and compare its current clinical management from two
      perspectives: that of a veterinarian specialized in infectious and parasitic
      diseases, and that of a physician specialized in infectious tropical diseases. We
      thus prepared a list of 10 key questions from epidemiology to control of the
      disease in both species: dogs and humans. This issue requires a concise and clear
      response to help animal and human health clinicians to improve their clinical
      management and understanding of this important zoonosis. Our ultimate aim is to
      update and bring together the information available backed by sound scientific
      evidence.

PMID- 29657003
TI  - In vitro bioassays used in evaluating plant extracts for tick repellent and
      acaricidal properties: A critical review.
AB  - Ticks are haematophagous arthropods which rank closely with mosquitoes in their
      capacity to transmit disease pathogens of importance to animals and humans.
      Current control of ticks is based on the routine use of synthetic chemicals
      administered to animals or their environment. However, years of use and overuse
      of these chemicals have resulted in the development of resistance in these
      parasites and negative environmental impacts, hence the need for cheaper, safer
      and more environmentally friendly alternatives with alternate modes of action.
      There has been a large interest in using plants for these purposes. Peer-reviewed
      articles on plants evaluated for their tick repellent and/or acaricidal
      activities against immature and adult stages of ticks were collected from nine
      scientific databases with the aim of reviewing the bioassays employed. Search
      words included "acaricidal", "tick repellent", "antitick assays" and
      "phytomedicine". Many different methods were used to determine repellency and
      acaricidal activity. These include, among a few others, petri dish, tick
      climbing, olfactometer, larval packet and immersion bioassays. Tick climbing
      repellency and adult immersion bioassays were most commonly used. Ethanol was the
      most widely used solvent and Rhipicephalus (Boophilus) microplus was the most
      commonly studied tick across all the reviewed papers. It is unclear whether the
      outcome of these experiments on a one-host tick can be applied to other species
      of ticks that infest animals and humans. Also, most of the assays on repellency
      did not discriminate between olfaction and tactile chemoreception-based
      repellency and though some of the observed methods were similar, results differ
      significantly. These aspects will need further evaluation. Standardized
      laboratory methods are required to enable the valid comparisons between results
      from different laboratories.

PMID- 29657004
TI  - Artemisinin and Artemisia annua leaves alleviate Eimeria tenella infection by
      facilitating apoptosis of host cells and suppressing inflammatory response.
AB  - Evasion strategies of intracellular parasites by hijacking cellular pathways, are
      necessary to ensure successful survival and replication. Eimeria tenella (E.
      tenella) has the ability to circumvent apoptosis of infected cells through
      increased expression of the transcriptional factor NF-kappaB and the anti
      apoptotic factor Bcl-xL during the development of second generation schizonts.
      Artemisinin (ART) and its original plant, the dried leaves of Artemisia annua
      (LAA) have been shown to be effective against avian coccidiosis, however, the
      underlying mechanism remains unclear. We showed that E. tenella infection
      promoted the expression of anti-apoptotic protein Bcl-2 and inhibited the
      expression of pro-apoptotic proteins Bax and cleaved caspase-3 at 60 h post
      infection (PI), with a higher ratio of Bcl-2 to Bax. Nevertheless, the expression
      trends of Bcl-2, Bax and caspase-3 were reversed at 120 h and 192 h PI. ART
      treatment significantly abrogated Bcl-2 expression, whereas it promoted the
      expression levels of Bax and cleaved caspase-3 at the three time points above.
      Additionally, ART remarkably suppressed the increased mRNA expressions of NF
      kappaB and interleukin-17A in ceca during infection by E. tenella. Compared with
      the ART treatment, LAA treatment exerted more improvements in clinical symptoms,
      promoting apoptosis and suppressing inflammatory response. These alterations
      caused by ART and LAA treatments were consistent with the reduced clinical
      diarrhea and pathological improvements in chicken ceca. Collectively, these
      results indicate that the inhibitory effects of ART or LAA on E. tenella
      infection may work through facilitating the apoptosis of infected host cells and
      inhibiting the inflammatory response.

PMID- 29657005
TI  - Comparison of six commercial antigen kits for detection of Dirofilaria immitis
      infections in canines with necropsy-confirmed heartworm status.
AB  - Patient-side test kits for detecting antigenemia in dogs associated with sexually
      mature female heartworms (Dirofilaria immitis) have been available for three
      decades, and these tests are continually updated and improved. To define the
      sensitivity (Se) and specificity (Sp) of contemporary antigen detection tests
      against cardiopulmonary D. immitis burden, we evaluated five patient-side kits
      Anigen Rapid One Step(r) (Bio note), SNAP(r) 4Dx Plus Test Kit (IDEXX),
      WITNESS(r) Heartworm Canine Heartworm Antigen Test Kit (Zoetis), VetScan(r)
      Canine Heartworm Rapid Test (Abaxis), and Solo Step(r) CH Canine Heartworm
      Antigen Test (Heska), and one microplate ELISA (DiroCHEK(r); Zoetis), using
      archived canine sera divided into five subclasses of female worms (0, 1-5, 6-20,
      21-40, and >40). The patient-side tests were performed once, side-by-side
      according to each manufacturer's protocol by personnel blinded to the D. immitis
      status of each dog. The overall Se and Sp of the patient-side kits was >=97.5 and
      =94.0%, respectively. For samples from dogs with 1-5, 6-20, and 21-40 D. immitis,
      the Se was between 96 and 100%, with a slight increase in Se in dogs with >=41
      worms. The agreement between tests for all subclasses of D. immitis burden was
      between 99 and 100%. The Se and Sp for the ELISA compared with the necropsy
      results of dogs was 99 and 96%, respectively. Agreement between each patient-side
      test and the ELISA was between 97 and 100%. All commercially available tests can
      give practitioners excellent patient-side information, allowing them to make
      informed decisions on the need for additional diagnostic work-up before
      instituting new or continuing D. immitis prophylaxis.

PMID- 29657006
TI  - Comparison between McMaster and Mini-FLOTAC methods for the enumeration of
      Eimeria maxima oocysts in poultry excreta.
AB  - Monitoring Eimeria shedding has become more important due to the recent
      restrictions to the use of antibiotics within the poultry industry. Therefore,
      there is a need for the implementation of more precise and accurate quantitative
      diagnostic techniques. The objective of this study was to compare the precision
      and accuracy between the Mini-FLOTAC and the McMaster techniques for quantitative
      diagnosis of Eimeria maxima oocyst in poultry. Twelve pools of excreta samples of
      broiler chickens experimentally infected with E. maxima were analyzed for the
      comparison between Mini-FLOTAC and McMaster technique using, the detection limits
      (dl) of 23 and 25, respectively. Additionally, six excreta samples were used to
      compare the precision of different dl (5, 10, 23, and 46) using the Mini-FLOTAC
      technique. For precision comparisons, five technical replicates of each sample
      (five replicate slides on one excreta slurry) were read for calculating the mean
      oocyst per gram of excreta (OPG) count, standard deviation (SD), coefficient of
      variation (CV), and precision of both aforementioned comparisons. To compare
      accuracy between the methods (McMaster, and Mini-FLOTAC dl 5 and 23), excreta
      from uninfected chickens was spiked with 100, 500, 1,000, 5,000, or 10,000 OPG;
      additional samples remained unspiked (negative control). For each spiking level,
      three samples were read in triplicate, totaling nine reads per spiking level per
      technique. Data were transformed using log10 to obtain normality and homogeneity
      of variances. A significant correlation (R = 0.74; p = 0.006) was observed
      between the mean OPG of the McMaster dl 25 and the Mini-FLOTAC dl 23. Mean OPG,
      CV, SD, and precision were not statistically different between the McMaster dl 25
      and Mini-FLOTAC dl 23. Despite the absence of statistical difference (p > 0.05),
      Mini-FLOTAC dl 5 showed a numerically lower SD and CV than Mini-FLOTAC dl 23. The
      Pearson correlation coefficient revealed significant and positive correlation
      among the four dl (p <= 0.05). In the accuracy study, it was observed that the
      Mini-FLOTAC dl 5 and 23 were more accurate than the McMaster for 100 OPG, and the
      Mini-FLOTAC dl 23 had the highest accuracy for 500 OPG. The McMaster and Mini
      FLOTAC dl 23 techniques were more accurate than the Mini-FLOTAC dl 5 for 5,000
      OPG, and both dl of the Mini-FLOTAC were less accurate for 10,000 OPG counts than
      the McMaster technique. However, the overall accuracy of the Mini-FLOTAC dl 23
      was higher than the McMaster and Mini-FLOTAC dl 5 techniques.

PMID- 29657007
TI  - Update on flea and tick associated diseases of cats.
AB  - There are multiple vector-borne diseases in cats, the most prominent being those
      transmitted by mosquitos, sand flies, fleas, and ticks. Many of the agents
      vectored by fleas or ticks have been grown or amplified from blood or have
      induced antibodies in the serum of normal cats or those with clinical signs like
      fever and will be the focus of this manuscript. As high as 80% of fleas collected
      from cats contain at least one organism that could induce illness in cats or
      people. Anaplasma phagocytophilum, Bartonella spp., Borrelia spp., Ehrlichia
      spp., hemoplasmas, and Rickettsia spp. infect cats and can be associated with
      clinical illness. Anaplasma phagocytophilum and B. burgdorferi are transmitted by
      Ixodes spp., Ehrlichia spp. and A. platys are transmitted by Rhipicephalus
      sanguineus. Fleas vector Bartonella spp., hemoplasmas, and R. felis. Recently, R.
      typhus was detected in cats in Spain. Lethargy and fever are common findings in
      cats with flea and tick borne diseases. Hemoplasmas are associated with hemolytic
      anemia. Moderate thrombocytopenia is associated with the tick-vectored agents.
      Polymerase chain reaction assays performed on blood collected in the acute phase
      of infection can be used to prove presence of the organisms. Doxycycline at 5
      mg/kg, PO, twice daily or 10 mg/kg, PO, daily can be effective for resolving the
      clinical signs. If doxycycline is ineffective or not tolerated, fluoroquinolones
      can be effective for treatment of clinical illness associated with Bartonella
      spp., hemoplasmas, and Rickettsia spp. Use of flea and tick control products is
      effective for blocking transmission of many of the agents.

PMID- 29657008
TI  - Investigations into the host specificity of Theileria taurotragi.
AB  - All Theileria parasites have definitive natural hosts that act as carriers.
      Incidental infections of uncommon hosts do occur raising questions regarding host
      specificity and its drivers. Reported hosts for Theileria taurotragi include
      bushbuck, cattle and eland. More recently T. taurotragi was detected in African
      buffalo, which may have implications for accurate diagnostics of T. parva. The
      current study therefore investigated the host specificity of T. taurotragi by
      developing a specific and sensitive real-time Taqman PCR assay. Animals were
      screened from areas where Rhipicephalus appendiculatus, the tick vector for both
      T. parva and T. taurotragi was present. While T. taurotragi was detected in
      cattle, eland, kudu and nyala, African buffalo (n = 352) was negative.
      Conversely, these same buffalo showed a prevalence of 72-100% for T. parva. While
      transmission of T. taurotragi to cattle was successful using the same infected
      tick batch, transmission to African buffalo did not occur. The results suggest
      that African buffalo is not a natural host of T. taurotragi and would probably
      not harbor anti-schizont antibodies against T. taurotragi. This would preclude T.
      taurotragi as possible source of cross-reactivity in the T. parva
      immunofluorescent antibody test. Host specificity of T. taurotragi for members of
      the Tragelaphini, but not buffalo also suggests that host specificity may have
      been an important driver in the speciation of the T. taurotragi clade. Different
      scenarios for co-evolution of host and parasite are discussed with implications
      for time of divergence for this Theileria clade.

PMID- 29657009
TI  - Molecular and biochemical characterization of Taenia solium alpha-enolase.
AB  - Enolase (EC 4.2.1.11) acts as a multifunctional enzyme in many organisms, being
      involved in metabolism, transcription regulation and pathogenesis. In the current
      study, the recombinant alpha-enolase from Taenia solium (His-Tseno) was prepared
      and antiserum against His-Tseno was generated in rabbits. Consequently, we
      analyzed the enzymatic characteristics, plasminogen binding activity, tissue
      localization and expression patterns of Tseno. The study demonstrated that the
      enzymatic activity of His-Tseno was enhanced at pH around 7.0-7.5 and affected by
      addition of metal ions. Kinetic measurements using 2-phospho-d-glycerate (2-PGA)
      substrates gave a specific activity of 60.72 +/- 0.84 U/mg and 1.1 mM of Km2-PGA
      value. Plasminogen binding assay showed that His-Tseno could bind to human
      plasminogen and generate plasmin activated by a tissue-type plasminogen activator
      (t-PA). In addition, the lysine analogue 6-aminocaproic acid (epsilon-ACA) could
      inhibit the binding of plasminogen to His-Tseno. Quantitative real-time PCR
      confirmed that Tseno was expressed 2.38 folds higher in the adult worms (p <
      0.05) than in the cysticerci. Further, an immunolocalization assay indicated that
      native Tseno was mainly distributed in the tegument and eggs of gravid proglottis
      from adult T. solium. In conclusion, Tseno executes the innate glycolytic
      function to supply energy for the growth, egg production, and even invasion of T.
      solium.

PMID- 29657010
TI  - Anthelmintic resistance: Management of parasite refugia for Haemonchus contortus
      through the replacement of resistant with susceptible populations.
AB  - Sheep production in tropical and temperate regions is hampered by the presence of
      Haemonchus contortus, the blood-sucking nematode that is the major cause of
      economic losses in small ruminant enterprises. The most limiting factor in the
      control of this parasitic disease is the steady progress of anthelmintic
      resistance worldwide. The search for control strategies that minimise the use of
      anthelmintics is therefore central to various efforts worldwide. One strategy is
      the introduction of susceptible parasites in refugia when these refugia are at
      low levels. This strategy could lead to a renewed possibility anthelmintics being
      effective. At farm level, this management practice could recover the use of
      anthelmintics in flocks with high levels of resistance. This review explores the
      possibility of replacing resistant H. contortus populations with susceptible ones
      through refugia management and. highlights the experiences of on-farm research
      attempts carried out in different geographical areas, reaching various degrees of
      success.

PMID- 29657011
TI  - Molecular differentiation and species composition of genus Culicoides biting
      midges (Diptera: Ceratopogonidae) in different habitats in southern China.
AB  - Culicoides biting midges (Diptera:Ceratopogonidae) cause a significant biting
      nuisance to humans, livestock, which are the biological vectors of a range of
      risky pathogens. Accurate illustration of vector play a key role in arthropod
      borne diseases surveillance. However, few studies have focused on the Culicoides,
      which caused bluetongue disease in 29 provinces of China since 1979. In this
      study, we assessed cytochrome oxidase subunit I (COI) mtDNA molecular marker for
      identification of ten major vector species and analyzed the Culicoides species
      community and diversity in different habitats. A total of 20,795 Culicoides
      samples collected from 11 sample sites were identified as 23 species belonging to
      7 subgenera. Sequences of COI gene worked well as barcodes for identifying all
      the determined specimen in this study and were comparable with the existing
      sequence data from GenBank. We first reported COI barcode sequences of C.
      morisitai, C. insignipennis and C. homotomus. Morphological identification of
      Culicoides spp. samples within southern China appears relatively robust and some
      unidentified species were required further study. Our study shows that the COI
      sequence data can be used as a tool to identify species of Culicoides in Jiangxi
      Province. In our sampled area, the most abundant species was C. arakawae
      (61.89%), followed by C. oxystoma (13.77%), C. punctatus (10.10%), C. nipponensis
      (8.82%), C. homotomus (3.19%) and C.morisitai (1.17%) in this study. C. punctatus
      was the dominant species of Park habitat (62.22%), C. arakawae was the
      predominant species of Chicken habitat (96.66%), Vegetable plot habitat (92.0%),
      and Peasant household habitat (83.21%), respectively. C. oxystoma was the
      abundant species of Residential area habitat (40.11%), Hospital habitat (56.65%),
      and Pig & Cow habitat (48.77%), respectively. Results also show that the
      potential Bluetongue virus vectors belong to the Obsoletus and Pulicaris groups,
      are also included and relatively abundant, notably: Culicoides punctatus. These
      findings expand the current knowledge of Culicoides population composition in the
      southern part of China.

PMID- 29657012
TI  - Antiprotozoal treatment of canine babesiosis.
AB  - Canine babesiosis is a tick-borne disease caused by several Babesia spp. which
      have different susceptebility to anti-protozoal drugs. A few drugs and drug
      combinations are used in the treatment of canine babesiosis often without
      complete parasite elimination leaving treated dogs as carriers which could
      relapse with clinical disease and also transmit infection further. Although the
      large form canine babesial species Babesia canis, Babesia vogeli and Babesia
      rossi are sensitive to the aromatic diamidines imidocarb dipropionate and
      diminazene aceturate, small form species such as Babesia gibsoni, Babesia
      conradae and Babesia vulpes (Theileria annae) are relatively resistant to these
      drugs and are treated with the combination of the hydroxynaphthoquinone
      atovaquone and the antibiotic azithromycin. Azithromycin and other antibiotics
      that have anti-protozoal properties target the apicoplast, a relict plastid found
      in protozoa, and exert a delayed death effect. The triple combination of
      clindamycin, diminazene aceturate and imidocarb dipropionate is also effective
      against B. gibsoni and used to treat atovaquone-resistant strains of this
      species. Novel drugs and the synergistic effects of drug combinations against
      Babesia infection should be explored further to find new treatments for canine
      babesiosis.

PMID- 29657013
TI  - In vitro and in vivo activity of hydrolyzed Saccharomyces cerevisiae against goat
      nematodes.
AB  - Haemonchus contortus is the most prevalent nematode in tropical and subtropical
      regions and is responsible for significant losses in small ruminant production
      systems. Control of this parasite is based on the use of synthetic anthelmintics;
      although effective, prolonged and indiscriminate use can select for populations
      of resistant nematodes. Hydrolyzed yeast can help prevent populations of
      nematodes and is low in cost. The present study aimed to evaluate the preventive
      effect of hydrolyzed yeast on H. contortus through in vitro and in vivo assays.
      In in vitro experiments, the yeast preparation was tested at different stages of
      the H. contortus life cycle via tests of egg hatchability, larval development,
      larval exsheathment and larval migration. Both eggs and L3 larvae were obtained
      from sheep artificially infected with a monospecific strain of H. contortus. In
      in vivo experiments, animals were treated with hydrolyzed yeast (53.4 mg/kg/BW),
      and fecal egg counts (FECs), feces culture and Famacha were performed. The yeast
      preparation inhibited larval exsheathment in a dose-dependent manner (IC95 of
      0.46 mg/mL), though no activity at the other stages of the H. contortus life
      cycle was observed. The hydrolyzed yeast preparation was able to reduce FECs in
      treated animals from D40 to D54 (p < 0.05), showing an average efficiency of 60%.
      The yeast exhibited preventive properties, and the IC95 value suggests that H.
      contortus is highly susceptible. Our results indicate that administration of
      hydrolyzed yeast, which is already used commercially in ruminant nutrition, is an
      alternative method for the control of nematodes, mainly H. contortus.

PMID- 29657014
TI  - Resistance delaying strategies on UK sheep farms: A cost benefit analysis.
AB  - UK guidelines for the sustainable control of parasites in sheep (SCOPS) were
      formulated with the primary aim of delaying development of anthelmintic
      resistance (AR) on UK sheep farms. Promoting their use requires the engagement
      and commitment of stakeholders. An important driver for behavioural change in
      sheep farmers is evidence of economic benefits. A recent evaluation of SCOPS
      guidance in practice demonstrated a significant reduction in anthelmintic use,
      suggesting economic benefits through a direct reduction in product and labour
      costs. However, in order to maintain production, a range of alternative control
      strategies are advised, resulting in additional costs to farmers and so a full
      cost benefit analysis of best practice management was undertaken. We allocated
      financial values to the management recommendations described in the SCOPS
      technical manual. Benefits were calculated using data for production variables
      and anthelmintic use measured during studies to evaluate the effect of SCOPS
      recommendations on 16 UK sheep farms and from other published work. As SCOPS
      control is not prescriptive and a range of different diagnostics are available,
      best and worst case scenarios were presented, comparing the cheapest methods
      (e.g. egg counts without larval culture) and management situations (e.g closed
      flocks not requiring quarantine treatments) with the most laborious and
      expensive. Simulations were run for farms with a small, medium or large flock
      (300; 1000; 1900 ewes) as well as comparing scenarios with and without potential
      production benefits from using effective wormers. Analysis demonstrated a
      moderate cost for all farms under both scenarios when production benefits were
      not included. A cost benefit was demonstrated for medium and large farms when
      production benefits were included and the benefit could be perceived as
      significant in the case of the large farms for the best case scenario (>L5000 per
      annum). Despite a significant potential reduction in anthelmintic use by farmers
      employing SCOPS guidance, the very low price of the older anthelmintic classes
      meant that the benefit did not always outweigh the additional
      management/diagnostic costs unless an increase in production was also achieved.
      This is an important finding. Focussing research on key innovations that will
      improve the cost effectiveness of diagnostic assays in a diagnostic driven
      control strategy, as well as designing treatment options that can improve
      production outcomes, and presenting them in a clear and transparent way, must be
      high priority goals. Coupling targeted research with improvements in the delivery
      of messages to the end user is important in the light of increasing global
      concerns over drug resistance.

PMID- 29657015
TI  - Are recreational areas a risk factor for tick paralysis in urban environments?
AB  - In Australia, tick paralysis in dogs (caused by a toxin in the saliva of Ixodes
      species during feeding) is a serious, distressing condition, and untreated it is
      often fatal. The aim of this study was to quantify the association between
      parkland (recreational or natural) in an urban area and the occurrence of canine
      tick paralysis. Brisbane, as a large urban centre located within the zone of
      paralysis tick habitat along the east coast of Australia, was selected as the
      study area. Postcodes selected for inclusion were those defined as being of an
      urban character (Australian Bureau of Statistics). The number of natural and
      recreational parkland polygons and total land area per postcode were derived.
      Tick paralysis case data for the selected postcodes were extracted from a
      national companion animal disease surveillance database. Between October 2010 and
      January 2017, 1650 cases of tick paralysis in dogs were reported and included in
      this study. Significant correlations were found between the number of reported
      cases per postcode and parklands: natural counts, 0.584 (P < 0.0001); natural
      area, 0.293 (P = 0.0075); recreational counts, 0.297 (P = 0.0151); and
      recreational area, 0.241 (P = 0.0286). Four disease clusters were also detected
      within the study area. All of these were located on the edges of the study area -
      either coastal or on the urban fringe; no clusters were identified within the
      core urban zone of the study area. Of the disease cases included in this study,
      strong seasonality was evidence: 68% of all cases were identified in spring.
      Within urban environments, areas of natural vegetation in particular appear to
      pose a risk for tick paralysis in dogs. This evidence can be used by
      veterinarians and dog owners to reduce the impact of tick paralysis by raising
      awareness of risk areas so as to enhance prevention via chemoprophylaxis and
      targeted searches of pet dogs for attached ticks.

PMID- 29657016
TI  - A behavioral evaluation of the effects of ingestion of Linguatula serrata nymphs
      in rats.
AB  - Nasopharyngeal linguatuliasis known as Halzoun or Marrara syndrome occurs
      following ingestion of raw or undercooked viscera, including lymph nodes, liver
      and lung of infected animals. The present study was aimed to investigate the
      behavioral changes induced by ingestion of Linguatula serrata nymphs in rats. For
      this purpose, 24 rats were divided into four groups and orally ingested with 0
      (control), 15, 30 and 60 L. serrata nymphs, respectively. Sneezing, mouth and
      tongue movements and mouth opening numbers were counted and the duration of mouth
      and nose grooming was measured at 10-min blocks for 30 min. Ingestion of 0
      (normal saline) number of nymph produced negligible behaviors, whereas 15, 30 and
      60 numbers of nymphs increased the above-mentioned behaviors when compared to
      normal saline (0 nymph) group. In this context, 60 number of nymphs produced more
      behavioral changes than 15 nymphs. We concluded that ingestion of L. serrata
      nymphs can produce behavioral changes in orofacial area in rats.

PMID- 29657017
TI  - Assessment of the antigenic and neuroprotective activity of the subunit anti
      Toxoplasma vaccine in T. gondii experimentally infected mice.
AB  - The aim of this study was to evaluate the immunogenic and immunoprotective
      activities and to determine the neuroprotective capacity of the tetravalent
      vaccine containing selected recombinant T. gondii antigens (ROP2 + ROP4 + SAG1 +
      MAG1) administered with safe adjuvants (MPL and alum) using male and female
      inbred mice. The tested antigenic combination provided partial protection against
      brain cyst formation, especially in males (reduction in cyst burden by 72%). The
      decrease in cyst burden was observed for the whole brain as well as for specified
      brain regions associated with natural defensive behaviors, emotion processing and
      integration of motor and sensory stimuli. The vaccine triggered a strong,
      specific immune response, regardless of sex, which was characterized by the
      antigen-specific in vitro synthesis of cytokines (IL-2, IFN-gamma and IL-10) and
      in vivo production of systemic IgG1 and IgG2a immunoglobulins. Immunization prior
      to the parasite challenge seemed to influence T. gondii - associated behavioral
      and neurochemical changes, although the impact of vaccination strongly depended
      on sex and time post-infection. Interestingly, in the vaccinated and T. gondii
      infected mice there was a significant delay in the parasite-induced loss of
      aversion toward cat smell (cats are the definitive hosts of the parasite). The
      regained attraction toward feline scent in vaccinated males, observed during
      chronic parasite invasion, correlated with the increase in the dopamine
      metabolism.

PMID- 29657018
TI  - Wolbachia, doxycycline and macrocyclic lactones: New prospects in the treatment
      of canine heartworm disease.
AB  - Melarsomine dihydrochloride (Immiticide(r), Merial) is the only approved
      adulticidal drug for the treatment of canine heartworm disease (HWD). However, in
      cases where arsenical therapy is not possible or is contraindicated, a monthly
      heartworm preventive along with doxycycline for a 4-week period, which targets
      the bacterial endosymbiont Wolbachia, might be considered. There are published
      reports on the efficacy of ivermectin and doxycycline in both experimentally and
      naturally infected dogs, but no data on the use of other macrocyclic lactones
      (MLs) with a similar treatment regime. Preliminary results of studies in dogs
      show that a topical formulation of moxidectin, the only ML currently registered
      as a microfilaricide, is also adulticidal when combined with doxycycline. It is
      not yet known if the efficacy of these combination therapies is due to
      pharmacokinetic synergism. A recent study showed that serum levels of doxycycline
      in dogs treated with the combination protocol were not statistically different
      compared to dogs treated with doxycycline alone. However, lungs from dogs treated
      with the combination therapy showed a marked reduction in T regulatory cells,
      indicating that treatment efficacy may be due to a heightened immune response
      against the parasite. Further studies are necessary to evaluate the long-term
      clinical outcome of combination protocols and to establish the most efficient
      treatment for HWD in dogs.

PMID- 29657019
TI  - Therapeutic vaccine of killed Leishmania amazonensis plus saponin reduced
      parasite burden in dogs naturally infected with Leishmania infantum.
AB  - A key goal in the control of canine visceral leishmaniosis (CVL) has been the
      development of vaccines with a highly protective capability to interrupt the
      parasite transmission cycle. However, in addition to promising vaccine searches,
      researchers have sought to develop new drugs capable of eliminating parasites in
      humans and dogs. With that in mind, this study analyzed an immunotherapeutic
      approach in dogs naturally infected with Leishmania infantum. Fourteen dogs were
      divided into two groups and received a protocol of immunotherapeutic treatment
      with five doses of total antigens of Leishmania amazonensis or total antigens of
      L. amazonensis plus saponin (LaSap). All the animals were evaluated before and 90
      and 180 days after treatment, hematology, liver and renal biochemical analyzes,
      serology, lymphoproliferation, and parasite load by qPCR. The results of
      immunotherapy with the LaSap vaccine were promising since it was able to preserve
      hematological and biochemical parameters, as well as improve the clinical status,
      reduce serum levels of IgG, induce a lymphoproliferative capacity against soluble
      antigens of L. infantum, and provide a marked reduction in the parasite load
      after LaSap immunotherapeutic treatment. The immunotherapy data demonstrated that
      LaSap offered the best formulation to induce clinical cure associated with a
      parasite load reduction in the skin. However, after 180 days of treatment, the
      animals again showed a slight increase in parasitism, indicating that
      immunotherapy does not promote sterilizing cure and a new immunotherapeutic
      intervention would be necessary to maintain low parasitism in dogs.

PMID- 29657020
TI  - Helicobacter pylori infection aggravates diet-induced nonalcoholic fatty liver in
      mice.
AB  - BACKGROUND: Previous epidemiological studies have suggested a link between
      Helicobacter pylori (H. pylori) infection and nonalcoholic fatty liver disease
      (NAFLD), yet animal studies are lacking to elucidate this association. In this
      study, we evaluated the potential effects of H. pylori infection on NAFLD in
      mice. METHODS: We first established two strains of H. pylori infected mice model
      with either chow diet or high fat diet (HFD). The body and liver weight, blood
      glucose, serum transaminases and lipid levels and markers of hepatic inflammation
      were measured. Histological analyses were also performed on liver tissue.
      Expressions of fat synthesis genes as well as insulin signaling proteins were
      also determined. RESULTS: After 24 weeks of treatment, the abdominal
      circumference, fasting blood glucose, low-density cholesterol and alanine
      transaminase were significantly increased in HFD feeding mice infected with H.
      pylori SS1 compared to HFD controls. Moreover, HFD fed mice infected with H.
      pylori SS1 showed significantly more liver steatosis. H. pylori SS1 infection
      inhibited phosphorylation of IRS1 and Akt and trended to increase the expression
      of IL-1beta and TNF-alpha in the liver. CONCLUSION: H. pylori infection is
      associated with NAFLD in C57BL/6 mice which depends on the bacterial strain and
      diet structure. The infection of H. pylori SS1 instead of NCTC11637 in
      combination with HFD induced more severe liver steatosis. H. pylori infection may
      play a role in NAFLD development and further studies are needed to determine
      whether H. pylori eradication can improve NAFLD risk.

PMID- 29657021
TI  - Corrigendum to "HDL-C, triglycerides and carotid IMT: A meta-analysis of 21,000
      patients with automated edge detection IMT measurement" [Atherosclerosis 232
      (2014) 65-71].

PMID- 29657022
TI  - Female epispadias: Single-stage approach - A technique to achieve continence.
AB  - This video provides a case report of a 3 year old girl with epispadia and the
      highlights of the surgery. A cystoscopic guided bladder neck plication was
      performed to achieve continence. Key points include: (1) Skin incision planning;
      (2) Cutaneous flap liberation to create a new urethra; (3) Complete bladder neck
      release to allow a controlled plication; (4) Use of cystoscopy to achieve the
      ideal bladder neck closure; (5) Bladder neck manipulation to achieve continence.

PMID- 29657023
TI  - Evolutionary Origins of the Differences in Osteoporosis Risk in US Populations.
AB  - Over the past 50 years, it has been increasingly evident that there are
      population differences in bone mass and the risk of osteoporosis. In the United
      States, many studies have reported a lower prevalence of osteoporosis in African
      Americans compared with people of European descent. If we trace the trajectory of
      changes in lifeways from the earliest migrations of early Homo out of Africa over
      the past two million years or so, to include lower vitamin D levels in higher
      latitudes; more meat in the diet; increasing sedentism; and a longer
      lifespan/longer postmenopausal period, it is not surprising that osteoporosis
      occurs more frequently in populations of European descent. While many scholars
      have explored the apparent "paradox" of higher bone mass, lower vitamin D levels,
      and higher parathyroid hormone levels among African Americans, this brief review
      of evolutionary shifts that affected our species may change the approach to
      understanding the current population differences in the United States.

PMID- 29657024
TI  - Vitamin D and Trabecular Bone Score in a Group of Young Lebanese Adults.
AB  - The relationship between vitamin D and trabecular bone score (TBS) in young
      adults remains unclear. The aim of this study was to explore the relationship
      between 25-hydroxyvitamin D [25(OH)D] serum levels and TBS in a healthy adult
      population. A total of 54 men and 61 women whose ages range from 18 to 35
      participated in the present study. Participants with 25(OH)D insufficiency
      (between 21 and 29 ng/mL) were 55.7%, and those with 25(OH)D deficiency (<=20
      ng/mL) were 11.4%. TBS positively correlated with 25(OH)D in men (r = 0.393; p
      <0.05) and women (r = 0.324; p < 0.05). In both genders, TBS was significantly
      higher in 25(OH)D-sufficient participants (>=30 ng/mL). The present study
      provides evidence that vitamin D positively affects bone health and suggests that
      maintaining adequate vitamin D status may be essential for optimal TBS values.

PMID- 29657025
TI  - Physical Fitness, Adiposity, and Diets as Surrogate Measures of Bone Health in
      Schoolchildren: A Biochemical and Cross-Sectional Survey Analysis.
AB  - This study aimed to investigate the associations between adiposity, muscular
      fitness (MF), diet, sun exposure, and physical activity profiles as surrogate
      measures with bone health status in a sample of schoolchildren aged 8-18 yr old.
      A total of 250 Egyptian schoolchildren aged 8-18 yr were randomly invited to
      participate in these cross-sectional survey analyses. Calcaneal broadband
      ultrasound attenuation (c-BUA), bone mineral density (BMD), and bone formation
      markers (total calcium, serum bone alkaline phosphatase, and osteocalcin) were
      measured as markers of bone health. Adiposity profile, MF, physical activity
      (PA), sun exposure, Ca, and vitamin D dietary intake as related cofactors of bone
      health were measured by using prevalidated questionnaires and standard analytical
      techniques. A total of 85% (n = 213) of the study population showed normal bone
      health and 14.8% (n = 37) had abnormal bone health; most of them are girls
      (67.6%) classified according to BMD and c-BUA Z-scores into osteopenia (9.6%) and
      osteoporosis (5.2%). Compared with boys, higher correlations between c-BUA, bone
      mineral content, and BMD measures in the femoral neck, lumbar spine, whole body,
      and bone markers were reported in girls with lower bone mass. There was a
      positive significant correlation between body mass index, adiposity, sun
      exposure, MF, PA status, Ca and vitamin D intake, and c-BUA and BMD score
      analyses. These parameters were shown to be associated with about ~57.3%-88.4% of
      bone health characteristics of children and adolescents with osteopenia and
      osteoporosis. In children and adolescents, sun exposure, Ca and vitamin D diets,
      adiposity, PA, and changes in the levels of Ca, osteocalcin, and serum bone
      alkaline phosphatase were shown to be associated with bone health. Also, a
      significant correlation was reported between c-BUA score, dual-energy X-ray
      absorptiometry-BMD measures, and bone markers at clinically important bone sites
      of girls and boys. However, further clinical trials should be studied to consider
      c-BUA and bone markers as the benchmark estimates of bone mass for diagnostic
      purposes in young ages.

PMID- 29657026
TI  - Muscular Maximal Strength Indices and Bone Variables in a Group of Elderly Women.
AB  - The aim of the present study was to explore the relations between muscular
      maximal strength indices and bone parameters (bone mineral density [BMD], hip
      geometry indices, and trabecular bone score [TBS]) in a group of elderly women.
      This study included 35 healthy elderly women whose ages range between 65 and 75
      yr (68.1 +/- 3.1 yr). BMD (in gram per square centimeter) was determined for each
      individual by dual-energy X-ray absorptiometry at the whole body, lumbar spine
      (L1-L4), total hip (TH), and femoral neck (FN). L1-L4 TBS and hip geometry
      indices were also evaluated by dual-energy X-ray absorptiometry. Maximal muscle
      strength of bench press (1-repetition maximum [RM] bench press), maximal muscle
      strength of leg press (1-RM leg press), and handgrip were measured using
      validated methods. 1-RM bench press was positively correlated to TH BMD (r =
      0.40; p < 0.05), FN BMD (r = 0.41; p < 0.05), FN section modulus (r = 0.33; p <
      0.05), and FN cross-sectional moment of inertia (r = 0.35; p < 0.05). 1-RM leg
      press was positively correlated to TH BMD (r = 0.50; p < 0.01), FN BMD (r = 0.35;
      p < 0.05), FN cross-sectional area (r = 0.38; p < 0.05), and TBS (r = 0.37; p <
      0.05). Handgrip was correlated only to FN cross-sectional moment of inertia (r =
      0.43; p < 0.01). This study suggests that 1-RM bench press and 1-RM leg press are
      positive determinants of BMD in elderly women.

PMID- 29657027
TI  - February 2018 (vol. 218, no. 2, page 244).

PMID- 29657028
TI  - Monosodium urate crystals induced ICAM-1 expression and cell-cell adhesion in
      renal mesangial cells: Implications for the pathogenesis of gouty nephropathy.
AB  - BACKGROUND: Renal disease is prevalent in gouty patients and monosodium urate
      (MSU) crystal deposition in the kidney can be detected in some gouty nephropathy
      patients. MSU crystals can induce inflammatory events, we investigated the MSU
      induced expression of intercellular adhesion molecule (ICAM)-1 on human renal
      mesangial cells (HRMCs) and the involved signal transduction mechanisms. METHODS:
      The HRMCs cell line was purchased from ScienCell Research Laboratories. MSU
      crystals were made by dissolving uric acid in sodium hydroxide (NaOH) solution.
      The involvement of MAPKs, apoptosis-associated speck-like protein containing a
      CARD domain (ASC), and Toll-like receptor (TLR) was investigated using
      pharmacological inhibitors, transfection with short hairpin RNA (shRNA), or
      monoclonal antibodies. Protein expression was evaluated by Western blotting. The
      functional activity of ICAM-1 was evaluated with cell-cell adhesion assay and
      immunofluorescence analysis. RESULTS: MSU stimulation increased expression of
      ICAM-1 and adhesion between HRMCs and human monocytic THP-1 cells. The
      interaction between HRMCs and THP-1 was suppressed by ICAM-1 neutralizing
      antibodies. MSU stimulation induced activation of mitogen-activated protein
      kinases, including c-Jun N-terminal kinase (JNK), p38, and extracellular signal
      regulated kinase (ERK), but only p38 was responsible for MSU-induced expression
      of ICAM-1 and cell-cell adhesion. ASC also play a role in MSU-induced effects.
      Pretreatment with monoclonal antibodies against toll-like receptor (TLR)2 or TLR4
      reduced MSU-induced ICAM-1 expression, cell-cell adhesion, p38 phosphorylation
      but the reduction of ASC activation is insignificant. CONCLUSION: The MSU induced
      ICAM-1 expression on HRMCs and cell-cell adhesion involved TLR2/4-p38-ICAM1
      pathway and TLR2/4 independent ASC-p38-ICAM1 axis. These findings might partly
      explain the mechanisms underlying gouty nephropathy.

PMID- 29657029
TI  - The Hormone FGF21 Stimulates Water Drinking in Response to Ketogenic Diet and
      Alcohol.
AB  - Alcohol and ketogenic diets increase water consumption. Here, we show that the
      hormone FGF21 is required for this drinking response in mice. Circulating levels
      of FGF21 are increased by alcohol consumption in humans and by both alcohol and
      ketogenic diets in mice. Pharmacologic administration of FGF21 stimulates water
      drinking behavior in mice within 2 hr. Concordantly, mice lacking FGF21 fail to
      increase water intake in response to either alcohol or a ketogenic diet. The
      effect of FGF21 on drinking is mediated in part by SIM1-positive neurons of the
      hypothalamus and is inhibited by beta-adrenergic receptor antagonists. Given that
      FGF21 also is known to suppress alcohol intake in favor of pure water, this work
      identifies FGF21 as a fundamental neurotropic hormone that governs water balance
      in response to specific nutrient stresses that can cause dehydration.

PMID- 29657030
TI  - Rewiring of Glutamine Metabolism Is a Bioenergetic Adaptation of Human Cells with
      Mitochondrial DNA Mutations.
AB  - Using molecular, biochemical, and untargeted stable isotope tracing approaches,
      we identify a previously unappreciated glutamine-derived alpha-ketoglutarate
      (alphaKG) energy-generating anaplerotic flux to be critical in mitochondrial DNA
      (mtDNA) mutant cells that harbor human disease-associated oxidative
      phosphorylation defects. Stimulating this flux with alphaKG supplementation
      enables the survival of diverse mtDNA mutant cells under otherwise lethal
      obligatory oxidative conditions. Strikingly, we demonstrate that when residual
      mitochondrial respiration in mtDNA mutant cells exceeds 45% of control levels,
      alphaKG oxidative flux prevails over reductive carboxylation. Furthermore, in a
      mouse model of mitochondrial myopathy, we show that increased oxidative alphaKG
      flux in muscle arises from enhanced alanine synthesis and release into blood,
      concomitant with accelerated amino acid catabolism from protein breakdown.
      Importantly, in this mouse model of mitochondriopathy, muscle amino acid
      imbalance is normalized by alphaKG supplementation. Taken together, our findings
      provide a rationale for alphaKG supplementation as a therapeutic strategy for
      mitochondrial myopathies.

PMID- 29657033
TI  - What to do when patients having a high risk of new-onset atrial fibrillation are
      identified?

PMID- 29657032
TI  - Referral for cardiac rehabilitation after acute myocardial infarction: Insights
      from nationwide AMIS Plus registry 2005-2017.
AB  - BACKGROUND: Referral rates for cardiac rehabilitation (CR) after an acute
      myocardial infarction (AMI) are low despite a Class I recommendation in the
      present guidelines. Therefore, we aimed to identify predictors for referral and
      patient characteristics from the national Swiss AMIS Plus registry. DESIGN AND
      METHODS: Data were extracted from the Swiss AMIS Plus registry between 2005 and
      2017, which included patients with ST-elevation myocardial infarction (STEMI) and
      Non-ST-elevation myocardial infarction (NSTEMI). For 32,416 patient (93.2%) data
      about destination at discharge were available with 10,940 (33.7%) having a
      recommendation for CR while 12,282 (37.9%) went home. 9194 (28.4%) were
      transferred to another hospital after index hospitalisation and were excluded.
      RESULTS: Patients referred to CR were younger (62.6 vs. 68.2 years) and had a
      higher prevalence of obesity (22.0% vs. 20.4%). Except for smoking (44.0% vs
      34.9%), they had less risk factors such as dyslipidemia (55.0% vs. 60.1%),
      hypertension (55.6% vs. 65.3%) and diabetes (16.7% vs. 21.5%). Patients with in
      hospital complications were more likely being referred for CR. Furthermore, STEMI
      (OR 1.61; CI 1.52-1.71), performed PCI (OR 2.65; CI 2.42-2.90) and Killip class
      >2 (OR 1.58; CI 1.36-1.84) favoured referral for CR, while age > 65 years,
      previous myocardial infarction, cerebrovascular disease or peripheral artery
      disease had a negative impact on referral for CR. CONCLUSIONS: Our data from
      23,222 patients after AMI demonstrate that in Switzerland patients referred for
      CR are younger, more obese with more STEMI. In-hospital complications were strong
      predictors for CR recommendation. Unlike anticipated, other risk factors were
      less present in CR patients.

PMID- 29657031
TI  - Warming Induces Significant Reprogramming of Beige, but Not Brown, Adipocyte
      Cellular Identity.
AB  - Beige and brown adipocytes generate heat in response to reductions in ambient
      temperature. When warmed, both beige and brown adipocytes exhibit morphological
      "whitening," but it is unknown whether or to what extent this represents a true
      shift in cellular identity. Using cell-type-specific profiling in vivo, we
      uncover a unique paradigm of temperature-dependent epigenomic plasticity of
      beige, but not brown, adipocytes, with conversion from a brown to a white
      chromatin state. Despite this profound shift in cellular identity, warm whitened
      beige adipocytes retain an epigenomic memory of prior cold exposure defined by an
      array of poised enhancers that prime thermogenic genes for rapid response during
      a second bout of cold exposure. We further show that a transcriptional cascade
      involving glucocorticoid receptor and Zfp423 can drive warm-induced whitening of
      beige adipocytes. These studies identify the epigenomic and transcriptional bases
      of an extraordinary example of cellular plasticity in response to environmental
      signals.

PMID- 29657034
TI  - Cost comparison across heart failure patients with reduced and preserved ejection
      fractions: Analyses of inpatient decompensated heart failure admissions.
AB  - BACKGROUND: Heart failure (HF) is the leading cause of inpatient admissions in
      the US for adults aged over 65 years and accounts for more than $17 billion in
      Medicare expenditures annually. There are limited published data on factors
      influencing expenditure and the relationship between cost and hospital length of
      stay. We sought to describe institutional costs of HF hospitalization, as well as
      demographic and clinical predictors of higher hospitalization costs in an
      academic hospital setting. METHODS AND RESULTS: Demographic and clinical
      information was collected retrospectively for 564 unique consecutive patients
      with a decompensated HF admission during 2010-2013. Forty-six percent had a
      baseline LVEF >40%, categorized as HF with preserved ejection fraction (HFpEF).
      Forty-three percent were female and the mean age was 71 years. Patients with
      reduced ejection fraction (HFrEF) were predominantly male, younger and had a
      lower burden of baseline comorbidities than HFpEF patients. Length of stay was
      longer for HFrEF (median 4 days) than HFpEF (median 3 days, p = 0.01). Mean total
      hospitalization cost was $9521. Mean costs trended higher for HFrEF patients than
      for HFpEF patients ($10,286 versus $8858, p = 0.07). Room and board contributed
      more than half of all costs. CONCLUSIONS: In this single-center study, we
      observed a trend towards higher HF hospitalization costs for patients with HFrEF,
      compared to HFpEF, even though patients with HFpEF are older and had more
      comorbid conditions. Costs were largely driven by length of stay, with higher
      heart rate at admission, lower systolic blood pressure, and higher creatinine
      associated with higher inpatient costs.

PMID- 29657035
TI  - Cardiac resynchronization therapy: How did consensus guidelines from Europe and
      the United States evolve in the last 15 years?
AB  - Cardiac resynchronization therapy (CRT) was proposed around 20 years ago, and its
      clinical use rapidly moved from pioneering experiences to randomized controlled
      trials (RCT). Since 2002 recommendations for CRT have been included in
      international consensus guidelines that even in an early phase recommended CRT as
      an effective treatment for improving symptoms, reducing hospitalizations and
      mortality in well-selected patients with wide QRS, left ventricular dysfunction
      and moderate to severe heart failure (NYHA classes III-IV), on optimal medical
      therapy. Subsequently the indications were extended to mild (NYHA class II) heart
      failure (associated with left ventricular dysfunction and wide QRS) and more
      recently also to appropriately selected patients with conventional indications
      for pacing having a left ventricular ejection fraction of 50% or less and NYHA
      class I-III. While all the guidelines strongly recommend CRT in case of LBBB with
      QRS duration >150 ms, lower strength of recommendations, with some heterogeneity,
      appears when QRS duration is 130-150 ms, especially if not associated with LBBB.
      Of note, according to recent guidelines, CRT is not recommended in case of QRS
      duration <130 ms, which is now the lower limit for candidacy to CRT, differently
      from the 120 ms limit used before. Despite consensus guidelines, many data
      indicate that CRT is still underused, with great heterogeneity in its
      implementation, both in North America and Europe, thus requiring a more organized
      patient referral.

PMID- 29657036
TI  - Serum irisin levels are associated with adverse cardiovascular outcomes in
      patients with acute myocardial infarction.
AB  - Irisin, a recently identified myokine, regulates mitochondrial function and
      energy expenditure. The concentration of irisin is significantly altered after ST
      elevation myocardial infarction (STEMI). We hypothesized that serum irisin
      concentration is associated with adverse cardiovascular outcomes after myocardial
      infarction. Serum irisin concentrations were measured using enzyme-linked
      immunosorbent assay (ELISA) in 399 patients 28d after the onset of STEMI in a
      prospective single-center cohort study. We assessed the association between
      irisin concentrations and adverse cardiovascular events during a 3-year follow
      up. The excess risks of cardiovascular mortality, stroke, heart failure, and
      revascularization were predominantly seen among those with the highest
      concentrations of irisin, with concentrations higher than 75th percentile of the
      overall distribution had a ~4-fold increase in risk (hazard ratio=3.96, 95%
      confidence interval 1.55 to 10.11, P<0.01). Our findings showed that serum
      concentrations of irisin are elevated in post-STEMI patients with increased risk
      for adverse cardiovascular events. Novel therapies targeting irisin may represent
      a new direction in the treatment of STEMI.

PMID- 29657037
TI  - Cardiac resynchronization therapy consensus guidelines: Evolution or revolution?

PMID- 29657038
TI  - Effect of exercise training on exercise capacity and quality of life in patients
      with heart failure.

PMID- 29657039
TI  - Should the distal tears of aortic dissection be treated? The risk of distal tears
      after proximal repair of aortic dissection.
AB  - BACKGROUND: Patients with distal residual after proximal repair of aortic
      dissection (AD) have shown unsatisfactory long-term prognosis. However, possible
      mechanisms and risk factors for distal aortic segmental enlargement (DSAE) have
      been poorly understood. METHODS: We analyzed 962 AD patients repaired to the
      descending aorta between 1999 and 2014. Aortic morphological characteristics of
      419 patients (including 75 DSAE and 344 non-DSAE patients) were investigated and
      compared. Potential risk factors associated with DSAE were explored using
      logistic regression analysis or natural logarithmic transformation. Logistic
      multi regress equations were performed to identify independent risk factors.
      RESULTS: Independent risk factors of DSAE are listed as follow: more tears in the
      thoracic descending aorta (odds ratio [OR], 1.65; 95% confidence interval
      [CI],1.24 to 2.19; P = .0005); fewer tears in the infra-renal abdominal aorta
      (OR, 3.00; 95% CI,2.04 to 4.55; P < .0001); closer distance of the first intimal
      tear to the left subclavian artery (OR, 1.51; 95% CI,1.28 to 1.69; P < .0001);
      larger average distance between tears (OR, 11.81; 95% CI,3.39 to 41.08; P =
      .0001); larger maximum distance between two tears (OR, 1.79; 95% CI,1.48 to 2.16;
      P < .0001), and larger area of remained tears (OR, 1.56; 95% CI, 1.38 to 1.76; P
      < .0001). CONCLUSIONS: The location and size of remained tears are the key risk
      factors of DSAE patients. Long-segment aortic repair and aggressive exclusion of
      all distal tears located on the thoracic descending aorta in their initial
      therapy will be an optimal strategy.

PMID- 29657040
TI  - Left ventricular volume and wall stress are linked to lung function impairment in
      COPD.
AB  - BACKGROUND: Cardiovascular comorbidities are common in chronic obstructive
      pulmonary disease (COPD). We examined the association between airflow limitation,
      hyperinflation and the left ventricle (LV). METHODS: Patients from the COPD
      cohort COSYCONET underwent evaluations including forced expiratory volume in 1 s
      (FEV1), forced vital capacity (FVC), effective airway resistance (Reff),
      intrathoracic gas volume (ITGV), and echocardiographic LV end-diastolic volume
      (LVEDV), stroke volume (LVSV), end-systolic volume (LVESV), and end-diastolic and
      end-systolic LV wall stress. Data from Visit 1 (baseline) and Visit 3 (18 months
      later) were used. In addition to comparisons of both visits, multivariate
      regression analysis was conducted, followed by structural equation modelling
      (SEM) with latent variables "Lung" and "Left heart". RESULTS: A total of 641
      participants were included in this analysis. From Visit 1 to Visit 3, there were
      significant declines in FEV1 and FEV1/FVC, and increases in Reff, ITGV and LV end
      diastolic wall stress, and a borderline significant decrease in LV mass. There
      were significant correlations of: FEV1% predicted with LVEDV and LVSV; Reff with
      LVSV; and ITGV with LV mass and LV end-diastolic wall stress. The SEM fitted the
      data of both visits well (comparative fit index: 0.978, 0.962), with strong
      correlation between "Lung" and "Left heart". CONCLUSIONS: We demonstrated a
      relationship between lung function impairment and LV wall stress in patients with
      COPD. This supports the hypothesis that LV impairment in COPD could be initiated
      or promoted, at least partly, by mechanical factors exerted by the lung disorder.

PMID- 29657041
TI  - The rule is: There are no rules.

PMID- 29657042
TI  - COPD - You'll never walk alone.

PMID- 29657044
TI  - Endothelial dysfunction as a common soil of lower urinary tract symptoms and
      cardiovascular disease.

PMID- 29657043
TI  - Endothelial dysfunction, abnormal vascular structure and lower urinary tract
      symptoms in men and women.
AB  - BACKGROUND: Lower urinary tract symptoms (LUTS) is not only common symptoms in
      elderly men and women but also risk of future cardiovascular events. The purpose
      of this study was to evaluate the relationships of vascular function and
      structure with LUTS in men and women. METHODS: We investigated flow-mediated
      vasodilation (FMD) and nitroglycerine-induced vasodilation (NID) as vascular
      function, brachial-ankle pulse wave velocity (baPWV) as vascular structure, and
      LUTS assessed by International Prostate Symptom Score (IPSS) in 287 men and 147
      women. RESULTS: IPSS was significantly correlated with traditional cardiovascular
      risk factors, Framingham risk score, FMD, NID and baPWV. Moderate to severe LUTS
      was associated with the prevalence of coronary heart disease in men but not in
      women. In men, FMD and NID were significantly lower in the moderate to severe
      LUTS group than in the none to mild LUTS group (2.1 +/- 2.0% vs. 4.0 +/- 3.0% and
      9.3 +/- 6.1% vs. 12.8 +/- 6.6%, P < 0.001, respectively). baPWV was significantly
      higher in the moderate to severe LUTS group than in the none to mild LUTS group
      (1722 +/- 386 cm/s vs. 1509 +/- 309 cm/s, P < 0.001). In multivariate analysis,
      FMD was independently associated with a decrease in the odds ratio of moderate to
      severe LUTS in men (OR: 0.83, 95% CI, 0.72-0.95; P = 0.008) but not in women. NID
      and baPWV were not independently associated with moderate to severe LUTS either
      in men or women. CONCLUSIONS: These findings suggest that endothelial dysfunction
      is associated with LUTS in men. LUTS in men may be useful for a predictor of
      cardiovascular events. CLINICAL TRIAL REGISTRATION INFORMATION: URL for Clinical
      Trial: http://UMIN; Registration Number for Clinical Trial: UMIN000003409.

PMID- 29657045
TI  - The relationship between left ventricular structure and function in the elite
      rugby football league athlete as determined by conventional echocardiography and
      myocardial strain imaging.
AB  - AIMS: The aims of this study were to establish the left ventricular (LV)
      phenotype in rugby football league (RFL) athletes and to mathematically model the
      association between LV size, strain (E) and ejection fraction (EF). METHODS AND
      RESULTS: 139 male athletes underwent echocardiographic LV evaluation including E
      imaging. Non-athletic males were used for comparison. All absolute and scaled
      structural indices were significantly larger (P < 0.05) in athletes with a
      predominance for normal LV geometry. EF and global E were similar between groups
      but strain rates (SR) were significantly lower (P < 0.05) in athletes. Lower
      apical rotation (P < 0.001) and twist (P = 0.010) were exhibited in athletes.
      CONCLUSION: Normal EF is explained by divergent effects of LV internal diastolic
      dimension (LVIDd) and mean wall thickness (MWT) on LV function. Reductions in SR
      and twist may be part of normal physiological LV adaptation in RFL athletes.

PMID- 29657046
TI  - Impact of cardiac hybrid imaging-guided patient management on clinical long-term
      outcome.
AB  - BACKGROUND: Although randomized trials have provided evidence for invasive
      fractional flow reserve to guide revascularization, evidence for non-invasive
      imaging is less well established. The present study investigated whether hybrid
      coronary computed tomography (CCTA)/single photon emission computed tomography
      (SPECT) myocardial perfusion imaging (MPI) can identify patients who benefit from
      early revascularization compared to medical therapy. METHODS: This retrospective
      study consists of 414 patients referred for evaluation of known or suspected
      coronary artery disease (CAD) with CCTA/SPECT hybrid imaging. CCTA categorized
      patients into no CAD, non-high-risk CAD and high-risk CAD. In patients with CAD
      (n = 329), a matched finding (n = 75) was defined as a reversible perfusion
      defect in a territory subtended by a coronary artery with CAD. All other
      combinations of pathologic findings were classified as unmatched (n = 254).
      Death, myocardial infarction, unstable angina requiring hospitalization, and late
      coronary revascularization were defined as major adverse cardiac events (MACE).
      Cox hazards models included covariates age, male gender, more than two risk
      factors, previous CABG, high-risk CAD and early revascularization. RESULTS:
      During median follow-up of 6.0 years, 112 patients experienced a MACE (27%).
      Early revascularization (n = 50) was independently associated with improved
      outcome among patients with a matched finding (p < 0.001). There was no benefit
      among patients with an unmatched finding (p = 0.787), irrespective of presence (p
      = 0.505) or absence of high-risk CAD (p = 0.631). CONCLUSIONS: Early
      revascularization is associated with an outcome benefit in CAD patients with a
      matched finding documented by cardiac hybrid imaging while no benefit of
      revascularization was observed in patients with an unmatched finding.

PMID- 29657047
TI  - Is there cardiac safety for the elite athletes?

PMID- 29657048
TI  - Cardiac hybrid imaging for the management of patients with known or suspected
      coronary artery disease.

PMID- 29657049
TI  - Prognostic implication of thermodilution coronary flow reserve in patients with
      indeterminate pressure-bounded coronary flow reserve.
AB  - BACKGROUND: Recently, the concept of pressure-bounded coronary flow reserve (PB
      CFR) has been introduced. However, using pressure-only data, a substantial
      proportion of patients could not be classified into high or low PB-CFR and
      remained as indeterminate PB-CFR. The current study evaluated the prognostic
      implication of thermodilution-based CFR (thermo-CFR) in patients with
      indeterminate PB-CFR. METHODS: Among 199 patients (211 lesions) with
      indeterminate PB-CFR, 170 patients (179 lesions) with deferral of
      revascularization were analyzed for the current study. The rates of patient
      oriented composite outcomes (POCO, a composite of all-cause mortality, any
      myocardial infarction, and any ischemia-driven revascularization) were compared
      according to thermo-CFR. All patients underwent fractional flow reserve (FFR) and
      thermo-CFR measurements. Thermo-CFR <= 2.0 was classified as low thermo-CFR. The
      median follow-up duration was 1350.0 (Q1-Q3 1252.0-1468.0) days. RESULTS: Mean
      angiographic percent diameter stenosis, FFR, and thermo-CFR were 42.3 +/- 13.9,
      0.84 +/- 0.06, and 3.10 +/- 1.15, respectively. Among 170 patients, 36 patients
      (21.2%) showed low thermo-CFR. Patients with low thermo-CFR showed significantly
      higher rate of POCO compared to those with high thermo-CFR (30.6% vs. 3.0%, HR
      12.117, 95% CI 3.854-38.091, p < 0.001). Adding thermo-CFR to a prediction model
      with FFR significantly increased discrimination and reclassification index for
      the risk of POCO (c-index 0.545 vs. 0.766, p = 0.002, category-free net
      reclassification index 1.169, p < 0.001, relative integrated discrimination index
      31.828, p < 0.001). CONCLUSIONS: Patients with low thermo-CFR showed a
      significantly higher risk of POCO compared to those with high thermo-CFR among
      patients with indeterminate PB-CFR. Thermo-CFR showed additional prognostic
      implication, in addition to FFR, in patients with indeterminate PB-CFR.

PMID- 29657050
TI  - Cardiac rehabilitation after acute myocardial infarction: Still insufficient
      referral!....

PMID- 29657051
TI  - Scoring atherosclerosis in the search of evidence-based personalized medicine.

PMID- 29657052
TI  - Coronary physiology and prognosis - What does pressure-bounded coronary flow
      reserve add?

PMID- 29657053
TI  - Takotsubo: One, no one and one hundred thousand diseases.

PMID- 29657054
TI  - Under which cardiac disease spectrum should takotsubo syndrome be classified?

PMID- 29657055
TI  - Totally endoscopic coronary artery bypass surgery: A meta-analysis of the current
      evidence.
AB  - BACKGROUND: Totally endoscopic coronary artery bypass (TECAB) has emerged as an
      alternative to other minimally invasive techniques. However, limited TECAB
      results are available to date. The purpose of this systematic review is to
      examine the existing literature to give an objective estimate of the outcomes of
      TECAB using a meta-analytical approach. METHODS: A comprehensive online review
      was performed in Ovid MEDLINE(r), Ovid EMBASE and The Cochrane Library from 2000
      to July 2017. Eligible studies included single arm TECAB studies as well as
      comparative studies (TECAB vs minimally invasive direct coronary artery bypass
      (MIDCAB)). Pooled event rates and odds ratios (ORs) for operative mortality,
      perioperative myocardial infarction (MI), perioperative stroke, graft patency and
      repeat revascularization were estimated. Single arm and pairwise comparisons were
      performed. RESULTS: Seventeen single arm TECAB articles (3721 patients, weighted
      mean follow-up 3.3years) were included. The pooled event rate was 0.80% (95%CI:
      0.60-1.2%) for operative mortality, 2.28% (95%CI: 1.7-3%) for perioperative MI,
      1.50% (95%CI: 1.1-2.0%) for perioperative stroke, 2.99% (95%CI: 1.6-5.4%) for
      repeat revascularization and 94.8% (95%CI: 89.3-97.5%) for early graft patency
      (weighted mean follow-up 10.1months). On pairwise meta-analysis 376 patients (263
      TECAB and 113 MIDCAB) were included. No difference in operative mortality
      (OR=0.25, 95%CI: 0.02-2.83), perioperative MI (OR=3.09, 95%CI: 0.37-26.12) or
      perioperative stroke (OR=1.33, 95%CI: 0.17-10.26) was found between the two
      techniques. CONCLUSIONS: TECAB has an acceptably low operative risk and a good
      early patency rate. The incidence of perioperative MI requires further
      investigation. The dearth of data comparing TECAB to open approaches compels the
      need for future comparative trials.

PMID- 29657056
TI  - Totally endoscopic coronary artery bypass grafting, the new frontier.

PMID- 29657057
TI  - Ventricular efficiency in pregnant women with congenital heart disease.
AB  - BACKGROUNDS: Pregnant women with congenital heart disease (CHD) are at risk of
      cardiovascular events during pregnancy as well as postpartum. The aim of our
      study is to address the feasibility of echocardiography-derived ventricular
      arterial coupling during pregnancy and postpartum among women with CHD. METHODS:
      In 31 pregnant women with CHD, we performed serial echocardiography at the first
      and third trimesters, early and late postpartum. The indices of contractility
      (single-beat determined end-systolic elastance, Eesab) and afterload (effective
      arterial elastance, Ea) were approximated on the basis of the systemic blood
      pressure and systemic ventricular volume. The ratio of stroke work and pressure
      volume area (SW/PVA) representing ventricular efficiency was also calculated.
      RESULTS: Age at the delivery was 28 (24-31) years. ZAHARA score was 0.75 (0.75
      1.50). Gestational age and birth weight of newborns were 38 (37-39) weeks and
      2.73 (2.42-2.92) kg, respectively. Heart rate, systemic ventricular end-diastolic
      volume and stroke volume significantly increased from the first trimester to the
      third trimester and reversed postpartum to the values of the first trimester.
      Eesab and Ea significantly decreased from the first trimester to the third
      trimester (Eesab; 4.90 [2.86-7.14] vs 3.41 [2.53-4.61] mm Hg/ml, p = 0.0001, Ea;
      2.83 [1.74-3.30] vs 2.18 [1.67-2.68] mm Hg/ml, p = 0.0012), and reversed early
      postpartum parallelly. Ejection fraction and SW/PVA remained unchanged throughout
      pregnancy and postpartum. CONCLUSIONS: Echocardiography-derived ventricular
      arterial coupling is feasible to understand ventricular function in pregnant
      women with CHD.

PMID- 29657058
TI  - Incremental prognostic value of coronary and systemic atherosclerosis after
      myocardial infarction.
AB  - BACKGROUND: The role of systemic atherosclerosis in myocardial infarction (MI)
      patients is not fully understood. We investigated the incremental prognostic
      value of coronary and systemic atherosclerosis after acute MI by estimating extra
      cardiac artery disease (ECAD) and extent of coronary atherosclerosis. METHODS AND
      RESULTS: The study included 544 prospective MI patients undergoing coronary
      angiography. For all patients, the longitudinal coronary atherosclerotic extent,
      expressed as Sullivan extent score (SES) was calculated. In addition, the
      patients underwent non-invasive screening for ECAD in the carotid, aortic, renal
      and lower limb. SES was found to be associated with ECAD independent of baseline
      clinical parameters [adjusted odds ratio (OR) 1.04 95% confidence interval (CI)
      1.02-1.06, P < 0.001]. Extensive systemic atherosclerosis, defined as the
      combination of extensive coronary disease (SES >= 17) and ECAD, was associated
      with higher risk for all-cause mortality compared to limited systemic
      atherosclerosis (SES < 17 and no ECAD) (hazard ratio [HR] 2.9 95% CI 1.9-4.5, P <
      0.001, adjusted for Global Registry of Acute Coronary Events risk score
      parameters 1.8, 95% CI 1.1-3.0, P = 0.019). The risk for the composite endpoint
      of cardiovascular death or hospitalization was significantly higher in patients
      with extensive systemic atherosclerosis compared to patients with limited
      systemic atherosclerosis (HR 3.1, 95% CI 2.1-4.7, P < 0.001, adjusted HR 1.9, 95%
      CI 1.2-3.1, P < 0.004). CONCLUSIONS: Visual estimation of the longitudinal
      coronary atherosclerotic extent at the time of MI predicts ECAD. Coexistence of
      extensive coronary disease and ECAD defines a group with particularly poor
      prognosis after MI.

PMID- 29657059
TI  - Pregnancy in women with congenital heart disease: Need for new techniques in
      hemodynamic monitoring.

PMID- 29657060
TI  - Characteristics and outcomes of ischemic stroke in patients with known atrial
      fibrillation or atrial fibrillation diagnosed after stroke.
AB  - BACKGROUND: It is unclear whether ischemic stroke patients with known atrial
      fibrillation (KAF) had different outcomes than those with atrial fibrillation
      diagnosed after stroke (AFDAS). We aimed to explore the characteristics and
      outcomes in ischemic stroke patients with KAF or AFDAS. METHODS: Consecutive
      patients hospitalized between 2000 and 2012 for first-ever stroke along with
      atrial fibrillation, either diagnosed before or during the stroke
      hospitalization, were identified from a nationwide claims database in Taiwan. The
      outcome of interest was a composite outcome of ischemic stroke, intracranial
      hemorrhage, or death within one year. Univariable and multivariable Cox
      regression analyses were used to determine the effect of KAF versus AFDAS on the
      composite outcome. RESULTS: We identified 1161 patients, of whom 481 (41.4%) had
      KAF and 680 (58.6%) had AFDAS. Age, sex, and stroke severity were similar between
      groups. However, patients with KAF had a higher prevalence of underlying heart
      diseases than those with AFDAS (67.2% versus 39.0%, p<0.001). In univariable
      analysis, patients with KAF had a higher risk of the composite outcome than those
      with AFDAS (hazard ratio [HR]: 1.42, 95% confidence interval [CI]: 1.13-1.79,
      p=0.003). In multivariable analysis, KAF was no longer independently associated
      with the composite outcome. CONCLUSIONS: As compared to ischemic stroke patients
      with AFDAS, those with KAF had a higher prevalence of underlying heart diseases.
      Whether AF was known before or diagnosed after stroke was not an independent
      predictor of the composite outcome.

PMID- 29657061
TI  - Risk factors for new-onset atrial fibrillation: A focus on Asian populations.
AB  - The incidence of new-onset atrial fibrillation (NOAF) is increasing both in the
      Asian populations and Western countries. Several demographic and clinical risk
      factors were independently associated with NOAF, including ageing, male sex,
      obesity, obstructive sleep apnea syndrome, hypertension, coronary artery disease,
      renal dysfunction and heart failure. However, some differences in the incidence
      of NOAF, the prevalence of some risk factors and lifestyle or environmental
      conditions may exist between Asian and Western countries. Early recognition and
      holistic management of risk factors in an integrated manner may help reduce the
      burden of NOAF and its complications. While some risk scores have been developed
      to predict the risk of NOAF, thus far none are currently recommended or
      adequately validated to be used as a screening tool especially in the Asian
      population. The present semi-systematic review article aims to provide a
      comprehensive overview on the risk factors associated to NOAF, focusing on those
      explored in the Asian populations.

PMID- 29657062
TI  - Disentangling the risk of atrial fibrillation detected after ischemic stroke
      (AFDAS): A real challenge in clinical practice.

PMID- 29657063
TI  - Does previous transanal excision for early rectal cancer impair surgical outcomes
      and pathologic findings of completion total mesorectal excision? Results of a
      systematic review of the literature.
AB  - BACKGROUND: Transanal excision (TAE) is increasingly used in the treatment of
      early rectal cancer because of lower rate of both postoperative complications and
      postsurgical functional disorders as compared with total mesorectal excision
      (TME) OBJECTIVE: To compare in a meta-analysis surgical outcomes and pathologic
      findings between patients who underwent TAE followed by completion proctectomy
      with TME (TAE group) for early rectal cancer with unfavorable histology or
      incomplete resection, and those who underwent primary TME (TME group). METHODS:
      The Medline and Cochrane Trials Register databases were searched for studies
      comparing short-term outcomes between patients who underwent TAE followed by
      completion TME versus primary TME. Studies published until December 2016 were
      included. The meta-analysis was performed using Review Manager 5.0 (Cochrane
      Collaboration, Oxford, UK). RESULTS: Meta-analysis showed that completion TME
      after TAE was significantly associated with increased reintervention rate
      (OR=4.28; 95% CI, 1.10-16.76; P<=0.04) and incomplete mesorectal excision rate
      (OR=5.74; 95% CI, 2.24-14.75; P<=0.0003), as compared with primary TME. However
      there both abdominoperineal amputation and circumferential margin invasion rates
      were comparable between TAE and TME groups. CONCLUSIONS: This meta-analysis
      suggests that previous TAE impaired significantly surgical outcomes and
      pathologic findings of completion TME as compared with primary TME. First
      transanal approach during completion TME might be evaluated in order to decrease
      technical difficulties.

PMID- 29657064
TI  - [Selective left mainstem bronchial intubation in the neonatal intensive care
      unit].
AB  - BACKGROUND: Selective neonatal left mainstem bronchial intubation to treat right
      lung disease is typically achieved with elaborate maneuvers, instrumentation and
      devices. This is often attributed to bronchial geometry which favors right
      mainstem entry of an endotracheal tube deliberately advanced beyond the carina.
      CASE SUMMARY: A neonate with severe bullous emphysema affecting the right lung
      required urgent non-ventilation of that lung. We achieved left mainstem bronchial
      intubation by turning the endotracheal tube 180 degrees  such that the Murphy's
      eye faced the left instead of the right, and simulated a left-handed intubation
      by slightly orientating the endotracheal tube such that its concavity faced the
      left instead of the right as in a conventional right-handed intubation.
      CONCLUSION: Urgent intubation of the left mainstem bronchus with an endotracheal
      tube can be easily achieved by recognizing that it is the position of the
      endotracheal tube tip and the direction of its concavity that are the chief
      determinants of which bronchus an endotracheal tube goes when advanced. This is
      important in critically ill neonates as the margin of safety and time window are
      small, and the absence of double-lumen tubes. Use of fiberoptic bronchoscope and
      blockers should be reserved as backup plans.

PMID- 29657065
TI  - Transfusion thresholds and red blood cells transfusion focused on tissue
      oxygenation.

PMID- 29657066
TI  - Hypoglycemia caused by insulinoma. A review of a case series treated at a
      tertiary hospital.

PMID- 29657067
TI  - Three ways for the same symptom: Syncope caused by myxoma.

PMID- 29657068
TI  - Safety and Efficacy of Day-case Percutaneous Nephrolithotomy: A Systematic Review
      from European Society of Uro-technology.
AB  - CONTEXT: Day case or ambulatory percutaneous nephrolithotomy (PCNL) has risen
      over the last few years with the aim of discharging patients within 24h.
      OBJECTIVE: We perform a systematic review of literature to evaluate the outcomes
      of day-case PCNL surgery. EVIDENCE ACQUISITION: A Cochrane style search was
      performed and the following bibliographic databases were accessed: PubMed,
      Science Direct, Scopus, and Web of Science. This was carried out in accordance
      with the Preferred Reporting Items for Systematic reviews and Meta-analyses
      (PRISMA) guidelines. All studies in the English language reporting on PCNL
      patients discharged within 24h were included. EVIDENCE SYNTHESIS: Based on the
      literature search of 97 articles, nine (502 patients) met the inclusion criteria
      (mean age: 47 yr), with a mean stone size of 20.5mm. The mean operating time was
      66min, and over a mean hospital stay of 17.5h, the stone-free rate was 95%. The
      overall complication rate was 13.5%; the vast majority of these complications
      were Clavien I-II complications, with a readmission rate of 3%. CONCLUSIONS: Day
      case PCNL is a safe and feasible strategy in carefully selected cases. However,
      for its success, detailed planning and adherence to surgical protocol are
      paramount with strict criteria for inpatient admission and a thorough follow-up
      plan. PATIENT SUMMARY: Day-case percutaneous nephrolithotomy procedure seems to
      be a safe procedure with good outcomes, and low risk of complications and
      readmissions. Detailed preoperative protocol and planning are paramount, with
      indications for inpatient admission as well as a thorough follow-up plan.

PMID- 29657069
TI  - Not all errors are the same: ERP sensitivity to error typicality in foreign
      accented speech perception.
AB  - Intercultural communication has become more and more frequent in the recent
      globalized society. When native listeners try to understand non-native speakers,
      they have to deal with different types of grammatical errors, some being
      frequently encountered and others being less common. The present Event-Related
      Potential (ERP) study investigated how native listeners process different types
      of morphosyntactic errors in foreign accented speech and whether they are
      sensitive to error typicality. Spanish natives listened to Spanish sentences in
      native and foreign (English) accent. ERPs were recorded in response to
      morphosyntactic violations that were commonly (gender errors) encountered in
      English accented Spanish or not (number errors). Although sentence comprehension
      accuracy did not differ across accents, the ERP responses changed as a function
      of accent and error type. In line with previous studies, gender and number
      violations in native accented speech elicited LAN-P600 responses. When speech was
      uttered by foreign speakers, number violations (uncommon errors) showed a P600
      effect, while gender violations (common errors) did not elicit late repair
      processes (reflected by the P600) but an N400 effect. The present results provide
      evidence that the neural time course of parsing depends not only on speaker's
      accent, but also on input error typicality.

PMID- 29657071
TI  - Re: Is a fractured mandible an emergency?

PMID- 29657070
TI  - Inclusion of the murine IgGkappa signal peptide increases the cellular
      immunogenicity of a simian adenoviral vectored Plasmodium vivax multistage
      vaccine.
AB  - INTRODUCTION: Cellular and humoral immune responses are both involved in
      protection against Plasmodium infections. The only malaria vaccine available,
      RTS,S, primarily induces short-lived antibodies and targets only a pre
      erythrocytic stage antigen. Inclusion of erythrocytic stage targets and enhancing
      cellular immunogenicity are likely necessary for developing an effective second
      generation malaria vaccine. Adenovirus vectors have been used to improve the
      immunogenicity of protein-based vaccines. However, the clinical assessment of
      adenoviral-vectored malaria vaccines candidates has shown the induction of robust
      Plasmodium-specific CD8+ but not CD4+ T cells. Signal peptides (SP) have been
      used to enhance the immunogenicity of DNA vaccines, but have not been tested in
      viral vector vaccine platforms. OBJECTIVES: The objective of this study was to
      determine if the addition of the SP derived from the murine IgGkappa light chain
      within a recombinant adenovirus vector encoding a multistage P. vivax vaccine
      candidate could improve the CD4+ T cell response. METHODS: In this proof-of
      concept study, we immunized CB6F1/J mice with either the recombinant simian
      adenovirus 36 vector containing the SP (SP-SAd36) upstream from a transgene
      encoding a chimeric P. vivax multistage protein or the same SAd36 vector without
      the SP. Mice were subsequently boosted twice with the corresponding recombinant
      proteins emulsified in Montanide ISA 51 VG. Immunogenicity was assessed by
      measurement of antibody quantity and quality, and cytokine production by T cells
      after the final immunization. RESULTS: The SP-SAd36 immunization regimen induced
      significantly higher antibody avidity against the chimeric P. vivax proteins
      tested and higher frequencies of IFN-gamma and IL-2 CD4+ and CD8+ secreting T
      cells, when compared to the unmodified SAd36 vector. CONCLUSIONS: The addition of
      the murine IgGkappa signal peptide significantly enhances the immunogenicity of a
      SAd36 vectored P. vivax multi-stage vaccine candidate in mice. The potential of
      this approach to improve upon existing viral vector vaccine platforms warrants
      further investigation.

PMID- 29657072
TI  - Appearance on face reading (cheek line) after orthognathic surgery.
AB  - The cheek line (face reading) is an aesthetic element of the facial profile. The
      purpose of our study was to investigate the changes in the cheek line after
      mandibular setback surgery. Forty patients (20 female and 20 male, mean (SD) age
      22 (5) years) were diagnosed with mandibular prognathism and treated by intraoral
      vertical ramus osteotomy alone. Cephalograms were obtained before operation (T1),
      at least a year postoperatively (T2), and final surgical changes over a year (T2
      T1). The cheek line and landmarks (soft and hard tissues) were compared using the
      paired t test. The hypothesis was that the cheek line did not change
      significantly after mandibular setback. At the time of the final follow-up (T2
      T1), the mean (SD) horizontal setback of pogonion (Pog) was 12.3 (3.5) mm for
      women and 11.7 (4.3) mm for men. The ratios of soft:hard tissue, labrale
      inferius:incisor inferius, labiomental sulcus:point B, soft tissue Pog:Pog, and
      cheek point:Pog in women were 0.96, 0.98, 0.98, and 0.08, and in men 0.91, 1.01,
      0.94, and 0.13, respectively. The nasolabial and cervicomental angles in women
      were significantly increased by 11.1 degrees  and 11.4 degrees , respectively,
      and in men the nasolabial angle was significantly increased by 11.1 degrees  and
      the mentolabial angle reduced by 9.9 degrees . The cheek line (T2-T1) was moved
      significantly forwards. The hypothesis was therefore rejected. In conclusion, the
      cheek line was advanced significantly after isolated mandibular setback.

PMID- 29657073
TI  - [Treatment of severe cutaneous adverse drug reactions].

PMID- 29657074
TI  - Nucleotide variability of protamine genes influencing bull sperm motility
      variables.
AB  - Protamines (PRMs), important proteins of chromatin condensation in
      spermiogenesis, are promising candidate genes to explore markers of sperm
      motility. The coding and in-silico predicted promoter regions of these genes were
      investigated in 102 crossbred and 32 purebred cattle. Also, mRNA quantification
      was done to explore its possibility as diagnostic tool of infertility. The PCR
      SSCP analysis indicated there were two band patterns only in fragment I of the
      PRM1 and fragment II of the PRM2 gene. The sequence analysis revealed A152G and
      G179A transitions in the PRM1 gene. Similarly, G35A, A49G and A64G transitions
      were identified in the PRM2 gene which resulted in altered amino acid sequences
      from arginine (R) to glutamine (Q), from arginine (R) to glycine (G) and from
      arginine (R) to glycine (G), respectively. This caused the reduction in molecular
      weight of PRM2 from 2157.66 to 1931.33 Da due to reduction in the number of basic
      amino acids. These altered properties of the PRM2 protein led to the reduction in
      Mass Motility (MM: P < 0.01), Initial Progressive Motility (IPM; P < 0.05) and
      Post Thaw Motility (PTM; P < 0.05) in crossbred bulls. The least squares analysis
      of variance indicated there was an effect of PRM2 haplotypes on MM (P = 0.0069),
      IPM (P = 0.0306) and PTM (P = 0.0500) in crossbred cattle and on PTM (P = 0.0408)
      in the overall cattle population. Based on the RT-qPCR analysis, however, there
      was not any significant variation of PRM1 and PRM2 gene expression among sperm of
      Vrindavani bulls with relatively lesser and greater sperm motility.

PMID- 29657075
TI  - Seminal plasma proteomes and sperm fertility.
AB  - During ejaculation, the spermatozoa are transported by the seminal plasma, a
      fluid resulting from secretions originating mainly from the prostate and the
      seminal vesicles in mammals. The interaction of the seminal plasma with
      spermatozoa induces binding of seminal proteins onto the sperm surface and
      membrane remodeling potentially impacting the sperm transport, survival and
      fertilizing ability in the female genital tract. The seminal plasma also contains
      peptides and proteins involved in the inflammatory and immune response of the
      female tract. Therefore the seminal plasma proteome has been investigated in a
      large range of taxa, including mammals, birds, fishes and insect species. The
      association of the seminal plasma with semen preservation or fertility identified
      proteic markers of seminal plasma function in domestic species. This review
      summarizes the current knowledge in seminal plasma proteomes and proteic markers
      of sperm preservation in animal species.

PMID- 29657076
TI  - Gasping for a Diagnosis: Pediatric Vocal Cord Dysfunction.
AB  - Vocal cord dysfunction is an obstruction of the upper airway, primarily on
      inspiration, due to the paradoxical adduction of the vocal cords. Vocal cord
      dysfunction continues to be underdiagnosed as its own entity. The lack of
      diagnosis can be attributed to the overlap of symptoms between asthma and
      exercise-induced bronchospasm. It is possible for patients diagnosed with asthma
      and/or exercise-induced bronchospasm to have underlying vocal cord dysfunction,
      which needs to be considered when prescribing asthma medications. This article
      will review the history of vocal cord dysfunction, the differential diagnosis,
      diagnostic testing, and the role of the nurse practitioner in caring for these
      patients.

PMID- 29657077
TI  - Reprint of: Marine OMEGA-3 fatty acids in the prevention of cardiovascular
      disease.
AB  - Omega-6 (omega6) and omega-3 (omega3) fatty acids are two classes of dietary
      polyunsaturated fatty acids derived from linoleic acid (18:2omega6) and alpha
      linolenic acid (18:3omega3), respectively. Enzymatic metabolism of linoleic and
      alpha-linolenic acids generates arachidonic acid (20:4omega6) and
      eicosapentaenoic acid (20:5omega3; EPA), respectively, both of which are
      substrates for enzymes that yield eicosanoids with multiple and varying
      physiological functions. Further elongation and desaturation of EPA yields the 22
      carbon fatty acid docosahexaenoic acid (22:6omega3; DHA). The main dietary source
      of EPA and DHA for human consumption is fish, especially oily fish. There is
      considerable evidence that EPA and DHA are protective against cardiovascular
      disease (heart disease and stroke), particularly in individuals with pre-existing
      disease. omega3 Fatty acids benefit multiple risk factors including blood
      pressure, blood vessel function, heart function and blood lipids, and they have
      antithrombotic, anti-inflammatory and anti-oxidative actions. omega3 Fatty acids
      do not adversely interact with medications. Supplementation with omega3 fatty
      acids is recommended in individuals with elevated blood triglyceride levels and
      patients with coronary heart disease. A practical recommendation for the general
      population is to increase omega3 fatty acid intake by incorporating fish as part
      of a healthy diet that includes increased fruits and vegetables, and moderation
      of salt intake. Health authorities recommend the general population should
      consume at least two oily fish meals per week.

PMID- 29657078
TI  - Reprint of: Antiproliferative activity of the Antrodia camphorata secondary
      metabolite 4,7-dimethoxy-5-methylbenzo[d][1,3]dioxole and analogues.
AB  - Both the traditional Chinese medicinal fungus, Antrodia camphorata, and its
      secondary metabolite, 4,7-dimethoxy-5-methylbenzo[d][1,3]dioxole, have been
      reported to possess promising anticancer activity. In this work the natural
      product and analogues bearing more polar substituents were synthesised and
      assessed for antiproliferative activity in the NCI-60 screen. Although each
      compound inhibited the growth of some cell lines at 10MUM, none had sufficient
      activity to warrant further investigation.

PMID- 29657079
TI  - Functional selectivity of cardiac preganglionic sympathetic neurones in the
      rabbit heart.
AB  - BACKGROUND: Studies have shown regional and functional selectivity of cardiac
      postganglionic neurones indicating there might exist a similar heterogeneity in
      spinal segmental preganglionic neurones, which requires further investigation.
      METHODS: Right and left sympathetic chains were electrically stimulated from T6
      to T1 in the innervated isolated rabbit heart preparation (n = 18). Sinus rate,
      left ventricular pressure, retrograde ventriculo-atrial conduction, monophasic
      action potential duration, effective refractory period, ventricular fibrillation
      threshold and electrical restitution were measured. RESULTS: Right sympathetic
      stimulation had a greater influence on heart rate (T1-T2: right; 59.9 +/- 6.0%,
      left; 41.1 +/- 5.6% P < 0.001) and left stimulation had greater effects on left
      ventricular pressure (T1-T2: right; 20.7 +/- 3.2%, left; 40.3 +/- 5.4%, P < 0.01)
      and ventriculo-atrial conduction (T1-T2: right; -6.8 +/- 1.1%, left; -15.5 +/-
      0.2%) at all levels, with greater effects at rostral levels (T1-T3). Left
      sympathetic stimulation caused shorter monophasic action potentials at the base
      (T4-T5: right; 119.3 +/- 2.7 ms, left; 114.7 +/- 2.5 ms. P < 0.05) and apex (T4
      T5: right; 118.8 +/- 1.2 ms, left; 114.6 +/- 2.6 ms. P < 0.05), greater
      shortening of effective refractory period (T4-T5: right; -3.6 +/- 1.3%, left; 
      7.7 +/- 1.8%. P < 0.05), a steeper maximum slope of restitution (T4-T5 base:
      right; 1.3 +/- 0.2, left; 1.8 +/- 0.2. P < 0.01. T4-T5 apex: right; 1.0 +/- 0.2,
      left; 1.6 +/- 0.3. P < 0.05) and a greater decrease in ventricular fibrillation
      threshold (T4-T5: right; -22.3 +/- 6.8%, left;-39.0 +/- 1.7%), with dominant
      effects at caudal levels (T4-T6). CONCLUSIONS: The preganglionic sympathetic
      efferent axons show functionally distinct pathways to the heart. The caudal
      segments (T4-T6) of the left sympathetic chain had a greater potential for
      arrhythmia generation and hence could pose a target for more focused clinical
      treatments for impairments in cardiac function.

PMID- 29657080
TI  - Right ventricular energetics and power in pulmonary regurgitation vs. stenosis
      using four dimensional phase contrast magnetic resonance.
AB  - OBJECTIVE: We investigated a full energetic profile of pressure and volume loaded
      right ventricle (RV) in porcine models by evaluating kinetic energy (KE), stroke
      power, power output and power loss across pulmonary valves with stenosis (PS) or
      with regurgitation (PR). METHODS: Fifteen pigs (6 PS and 6 PR, 3 unoperated
      controls) were studied. Phase-contrast 4D-flow MRI was performed in models of PS
      and PR at baseline and at 10-12 weeks, in conjunction with cardiac
      catheterization. Phase contrast velocities over 1 cardiac cycle were registered
      with a dynamic mask of the RV segmented from cine images. Mean KE and KE curve
      profiles were measured, normalized for RV volumes and compared between groups.
      Right heart catheterization pressures were used to calculate RV stroke power and
      power output, from which pulmonary valve power loss and RV power output ratio
      were calculated, and compared between groups. RESULTS: PS and PR groups had
      similar KE pre procedure but significant changes in KE post procedure. The PR
      group had higher RV power output ratio and KE (72.1% +/- 11.4%; 20.6 +/- 6.1)
      than PS group (25.6% +/- 4.7%; 13.8 +/- 5.0) post procedure. Volume loaded RV
      from PR had higher KE and power output ratio compared to pressure load from PS.
      CONCLUSIONS: In porcine models of PS and PR, the RV presents altered systolic and
      diastolic energetic profiles. Pulmonary valve efficiency appeared to decrease in
      the medium term with somatic growth, with increased power loss in all groups
      studied, and greatly within the PS group.

PMID- 29657081
TI  - Effect of chemical and physical heterogeneities on colloid-facilitated cesium
      transport.
AB  - A set of column experiments was conducted to investigate the chemical and
      physical heterogeneity effect on colloid facilitated transport under slow pore
      velocity conditions. Pore velocities were kept below 100 cm d-1 for all
      experiments. Glass beads were packed into columns establishing four different
      conditions: 1) homogeneous, 2) mixed physical heterogeneity, 3) sequentially
      layered physical heterogeneity, and 4) chemical heterogeneity. The homogeneous
      column was packed with glass beads (diameter 500-600 MUm), and physical
      heterogeneities were created by sequential layering or mixing two sizes of glass
      bead (500-600 MUm and 300-400 MUm). A chemical heterogeneity was created using
      25% of the glass beads coated with hydrophobic molecules (1H-1H-2H-2H
      perfluorooctyltrichlorosilane) mixed with 75% pristine glass beads (all 500-600
      MUm). Input solution with 0.5 mM CsI and 50 mg L-1 colloids (1-MUm diameter SiO2)
      was pulsed into columns under saturated conditions. The physical heterogeneity in
      the packed glass beads retarded the transport of colloids compared to homogeneous
      (R = 25.0), but showed only slight differences between sequentially layered (R =
      60.7) and mixed heterogeneity(R = 62.4). The column with the chemical,
      hydrophobic/hydrophilic, heterogeneity removed most of the colloids from the
      input solution. All column conditions stripped Cs from colloids onto the column
      matrix of packed glass beads.

PMID- 29657082
TI  - Horner's syndrome following obstetric neuraxial blockade - a systematic review of
      the literature.
AB  - Horner's syndrome is a rarely reported complication of neuraxial blockade. In
      obstetric practice, the neurological signs of Horner's syndrome may cause anxiety
      amongst patients and healthcare staff, but more importantly may herald the onset
      of maternal hypotension. Medline, CINAHL, and EMBASE databases were searched to
      identify cases of Horner's syndrome following obstetric neuraxial blockade.
      Anaesthetic technique, clinical features, anaesthetic management of the Horner's
      syndrome and time to resolution were assessed. Seventy-eight case reports of
      Horner's syndrome following obstetric neuraxial blockade were identified. Nine
      cases also had trigeminal nerve palsy and one case had hypoglossal nerve palsy.
      Amongst the 78 cases, 74% developed Horner's syndrome within one hour of a local
      anaesthetic bolus. The median time for resolution of Horner's syndrome was two
      hours, though one case was permanent. One case of Horner's syndrome was found to
      be due to an internal carotid artery dissection. Some cases of Horner's syndrome
      resolved spontaneously despite ongoing administration of epidural local
      anaesthetic. Hypotension was reported in 13%. Horner's syndrome is usually a
      benign phenomenon, the consequence of high cephalad spread of local anaesthetic,
      that resolves spontaneously within a few hours. Patients with a persistent
      Horner's syndrome, or one associated with atypical features such as neck pain,
      should undergo a diagnostic workup including magnetic resonance angiography of
      the neck. The dermatomal level of neuraxial blockade, maternal and fetal well
      being should be taken into account when making decisions regarding neuraxial
      blockade. The presence of Horner's syndrome alone should not lead to
      discontinuation of neuraxial blockade.

PMID- 29657084
TI  - Aggregated Abeta1-42 Is Selectively Toxic for Neurons, Whereas Glial Cells
      Produce Mature Fibrils with Low Toxicity in Drosophila.
AB  - The basis for selective vulnerability of certain cell types for misfolded
      proteins (MPs) in neurodegenerative diseases is largely unknown. This knowledge
      is crucial for understanding disease progression in relation to MPs spreading in
      the CNS. We assessed this issue in Drosophila by cell-specific expression of
      human Abeta1-42 associated with Alzheimer's disease. Expression of Abeta1-42 in
      various neurons resulted in concentration-dependent severe neurodegenerative
      phenotypes, and intraneuronal ring-tangle-like aggregates with immature fibril
      properties when analyzed by aggregate-specific ligands. Unexpectedly, expression
      of Abeta1-42 from a pan-glial driver produced a mild phenotype despite massive
      brain load of Abeta1-42 aggregates, even higher than in the strongest neuronal
      driver. Glial cells formed more mature fibrous aggregates, morphologically
      distinct from aggregates found in neurons, and was mainly extracellular. Our
      findings implicate that Abeta1-42 cytotoxicity is both cell and aggregate
      morphotype dependent.

PMID- 29657083
TI  - The course of awake breathing disturbances across the lifespan in Rett syndrome.
AB  - Rett syndrome (RTT), an X-linked dominant neurodevelopmental disorder caused by
      mutations in MECP2, is associated with a peculiar breathing disturbance
      exclusively during wakefulness that is distressing, and can even prompt emergency
      resuscitation. Through the RTT Natural History Study, we characterized cross
      sectional and longitudinal characteristics of awake breathing abnormalities in
      RTT and identified associated clinical features. Participants were recruited from
      2006 to 2015, and cumulative lifetime prevalence of breathing dysfunction was
      determined using the Kaplan-Meier estimator. Risk factors were assessed using
      logistic regression. Of 1205 participants, 1185 had sufficient data for analysis,
      including 922 females with classic RTT, 778 of whom were followed longitudinally
      for up to 9.0 years, for a total of 3944 person-years. Participants with classic
      or atypical severe RTT were more likely to have breathing dysfunction (nearly
      100% over the lifespan) compared to those with atypical mild RTT (60-70%).
      Remission was common, lasting 1 year on average, with 15% ending the study in
      terminal remission. Factors associated with higher odds of severe breathing
      dysfunction included poor gross and fine motor function, frequency of
      stereotypical hand movements, seizure frequency, prolonged corrected QT interval
      on EKG, and two quality of life metrics: caregiver concern about physical health
      and contracting illness. Factors associated with lower prevalence of severe
      breathing dysfunction included higher body mass index and head circumference Z
      scores, advanced age, and severe scoliosis or contractures. Awake breathing
      dysfunction is common in RTT, more so than seizures, and is associated with
      function, quality of life and risk for cardiac dysrhythmia.

PMID- 29657085
TI  - Structural Determinants for Small-Molecule Activation of Skeletal Muscle AMPK
      alpha2beta2gamma1 by the Glucose Importagog SC4.
AB  - The AMP-activated protein kinase (AMPK) alphabetagamma heterotrimer regulates
      cellular energy homeostasis with tissue-specific isoform distribution. Small
      molecule activation of skeletal muscle alpha2beta2 AMPK complexes may prove a
      valuable treatment strategy for type 2 diabetes and insulin resistance. Herein,
      we report the small-molecule SC4 is a potent, direct AMPK activator that
      preferentially activates alpha2 complexes and stimulates skeletal muscle glucose
      uptake. In parallel with the term secretagog, we propose "importagog" to define a
      substance that induces or augments cellular uptake of another substance. Three
      dimensional structures of the glucose importagog SC4 bound to activated
      alpha2beta2gamma1 and alpha2beta1gamma1 complexes reveal binding determinants, in
      particular a key interaction between the SC4 imidazopyridine 4'-nitrogen and
      beta2-Asp111, which provide a design paradigm for beta2-AMPK therapeutics. The
      alpha2beta2gamma1/SC4 structure reveals an interaction between a beta2 N-terminal
      alpha helix and the alpha2 autoinhibitory domain. Our results provide a structure
      function guide to accelerate development of potent, but importantly tissue
      specific, beta2-AMPK therapeutics.

PMID- 29657086
TI  - Structural Insights into a Flavin-Dependent [4 + 2] Cyclase that Catalyzes trans
      Decalin Formation in Pyrroindomycin Biosynthesis.
AB  - Here, we provide structural insights into PyrE3, a flavin-dependent [4 + 2]
      cyclase that catalyzes trans-decalin formation in the biosynthesis of
      pyrroindomycins. PyrE3 shares an architecture/domain organization head-to-tail
      similarity with the members of the family of para-hydroxybenzoate hydroxylase
      (pHBH)-fold monooxygenases, and possesses a flavin adenine dinucleotide (FAD)
      binding domain, a middle domain, and a C-terminal thioredoxin-like domain. The
      FAD-binding domain forms a central hub of the protein structure, and binds with
      FAD in a "closed" conformation of pHBH-fold family monooxygenases known for their
      highly dynamic catalytic processes. FAD plays an essential structural role in
      PyrE3, where it is amenable to redox change; however, redox change has little
      effect on [4 + 2] cyclization activity. PyrE3 appears to selectively accommodate
      a tetramate-containing, linear polyene intermediate in a highly positively
      charged pocket, which is located at the interface between the FAD-binding domain
      and the middle domain, and can accelerate trans-decalin formation likely through
      an endo-selective [4 + 2] transition state.

PMID- 29657087
TI  - The Pediatric Aerodigestive Center as a Tertiary Care-Based Medical Home: A
      Proposed Model.
AB  - Children with special healthcare needs have been identified nationally as a
      population whose health care is associated with unmet needs; increased morbidity;
      fragmentation of care and medical errors; caregiver dissatisfaction; and
      disproportionately high costs. A subset of these children are medically fragile,
      with medical complexity that requires a reliance on tertiary care-based services
      including subspecialty appointments, surgical procedures, and care coordination
      resources. For medically complex patients affected by upper and lower respiratory
      tract and gastrointestinal disorders, multidisciplinary aerodigestive centers
      have emerged at tertiary care centers across the United States to facilitate
      coordinated, high-quality, and high value care. We propose that the aerodigestive
      center is an effective vehicle for a tertiary care-based medical home. Within
      this model, the integration of a general pediatrician will help promote holistic,
      patient-centered care, and the general pediatrician can serve to both support and
      provide continuity with the primary care medical home.

PMID- 29657089
TI  - Mechanistic target of rapamycin (MTOR) protein expression in the tumor and its
      microenvironment correlates with more aggressive pathology at cystectomy.
AB  - BACKGROUND: The mechanistic target of rapamycin (mTOR) has been implicated in
      driving tumor biology in multiple malignancies, including urothelial carcinoma
      (UC). We investigate how mTOR and phosphorylated mTOR (pmTOR) protein expression
      correlate with chemoresponsiveness in the tumor and its microenvironment at final
      pathologic staging after neoadjuvant chemotherapy (NAC). METHODS: A single
      institution retrospective analysis was performed on 62 patients with cT2-4Nany UC
      undergoing NAC followed by radical cystectomy. Diagnostic (transurethral
      resection specimens, TURBT) and postchemotherapy radical cystectomy specimens
      were evaluated for mTOR and pmTOR protein expression using immunohistochemistry
      of the tumor, peritumoral stroma, and normal surrounding stroma. Protein
      expression levels were compared between clinical and pathologic stage. Whole
      transcriptome analysis was performed to evaluate mRNA expression relative to mTOR
      pathway activation. RESULTS: Baseline levels of mTOR and pmTOR within TURBT
      specimens were not associated with clinical stage and response to chemotherapy
      overall. Nonresponders with advanced pathologic stage at cystectomy (ypT2
      4/ypTanyN+) had significantly elevated mTOR tumor staining (P = 0.006) and a
      sustained mTOR and pmTOR staining in the peritumoral and surrounding normal
      stroma (NS). Several genes relevant to mTOR activity were found to be up
      regulated in the tumors of nonresponders. Remarkably, complete responders at
      cystectomy (ypT0) had significant decreases in both mTOR and pmTOR protein
      expression in the peritumoral and normal stroma (P = 0.01-0.03). CONCLUSIONS: Our
      results suggest that mTOR pathway activity is increased in tumor and sustained in
      its microenvironment in patients with adverse pathologic findings at cystectomy.
      These findings suggest the relevance of targeting this pathway in bladder cancer.

PMID- 29657090
TI  - Stauffer's syndrome: A comprehensive review and proposed updated diagnostic
      criteria.
AB  - BACKGROUND: Stauffer's syndrome corresponds to a set of clinical and analytical
      changes of paraneoplastic nature firstly recognized more than 50 years ago, in
      association to renal cell carcinoma. A definitive review including universal
      diagnostic criteria and updated knowledge since the original description is
      lacking. BASIC PROCEDURES: The authors conducted a comprehensive bibliographical
      review and propose updated diagnostic criteria to standardize diagnosis for
      clinical practice purposes and avoid misclassification. MAIN FINDINGS: Although
      having been described in association with renal cell carcinoma, the syndrome has
      been reported in correlation with other malignancies-either solid or
      hematological tumors. Additionally, a variant syndrome presenting with jaundice
      has also been characterized, but appears to have a similar clinical course to
      that of the classical Stauffer's syndrome. Although often described as rare, it
      may be more frequent than previously recognized. Stauffer's syndrome
      etiopathogenesis is still poorly understood, but immune mechanisms seem to play a
      role underscored by the malignancies to which the syndrome is associated, several
      of which having immunotherapy drugs approved for their treatment. PRINCIPAL
      CONCLUSIONS: A set of diagnostic criteria should be used to simplify, broaden and
      standardized diagnosis, under the entity characterized by reversible
      paraneoplastic intrahepatic cholestasis. Clinicians should be aware of the
      syndrome, namely consider further investigation if a plausible cause for
      unexplained intrahepatic cholestasis in an otherwise healthy patient is not
      found. Even though no universal approach is available, investigation should be
      considered regarding metastatic disease after resection of a primary tumor which
      has revealed persistence or recurrence of symptoms.

PMID- 29657088
TI  - Monocarboxylate transporters MCT1 and MCT4 are independent prognostic biomarkers
      for the survival of patients with clear cell renal cell carcinoma and those
      receiving therapy targeting angiogenesis.
AB  - BACKGROUND: Prognostic biomarkers for patients with clear cell renal cell
      carcinoma (ccRCC), particularly those receiving therapy targeting angiogenesis,
      are not well established. In this study, we examined the correlations of
      monocarboxylate transporter 1 (MCT1) and MCT4, 2 critical transporters for
      glycolytic metabolism, with various clinicopathological parameters as well as
      survival of patients with ccRCC and those treated with vascular endothelial
      growth factor receptor (VEGFR) inhibitors. METHODS: A cohort of 150 ccRCC
      patients were recruited into this study. All patients underwent radical or
      partial nephrectomy as the first-line treatment, and 38 received targeted therapy
      (sorafenib or sunitinib) after the surgery. Expression levels of MCT1, MCT4, and
      CD34 were examined by immunohistochemistry. Correlations between MCT1 or MCT4
      expression and different clinicopathological parameters or patient survival were
      analyzed among all as well as patients receiving targeted therapy. RESULTS: MCT1
      or MCT4 expression did not significantly correlate with sex, age, tumor diameter,
      microvascular density, tumor staging, pathological Furmann grade, or MSKCC
      (P>0.05). High expression of either MCT1 or MCT4 significantly correlated with
      reduced overall survival (OS) and progression-free survival (PFS) among the total
      cohort of ccRCC patients. For patients receiving targeted therapy, high
      expression of either MCT1 or MCT4 significantly correlated with reduced PFS, but
      not OS. Both conditions were independent prognostic biomarkers for reduced PFS
      among all patients or those receiving targeted therapy. CONCLUSION: MCT1 and MCT4
      are prognostic biomarkers for patients with ccRCC or those receiving targeted
      therapy. High expression of these 2 proteins predicts reduced PFS in these
      patients.

PMID- 29657091
TI  - Injectable polypeptide hydrogels via methionine modification for neural stem cell
      delivery.
AB  - Injectable hydrogels with tunable physiochemical and biological properties are
      potential tools for improving neural stem/progenitor cell (NSPC) transplantation
      to treat central nervous system (CNS) injury and disease. Here, we developed
      injectable diblock copolypeptide hydrogels (DCH) for NSPC transplantation that
      contain hydrophilic segments of modified l-methionine (Met). Multiple Met-based
      DCH were fabricated by post-polymerization modification of Met to various
      functional derivatives, and incorporation of different amino acid comonomers into
      hydrophilic segments. Met-based DCH assembled into self-healing hydrogels with
      concentration and composition dependent mechanical properties. Mechanical
      properties of non-ionic Met-sulfoxide formulations (DCHMO) were stable across
      diverse aqueous media while cationic formulations showed salt ion dependent
      stiffness reduction. Murine NSPC survival in DCHMO was equivalent to that of
      standard culture conditions, and sulfoxide functionality imparted cell non
      fouling character. Within serum rich environments in vitro, DCHMO was superior at
      preserving NSPC stemness and multipotency compared to cell adhesive materials.
      NSPC in DCHMO injected into uninjured forebrain remained local and, after 4
      weeks, exhibited an immature astroglial phenotype that integrated with host
      neural tissue and acted as cellular substrates that supported growth of host
      derived axons. These findings demonstrate that Met-based DCH are suitable
      vehicles for further study of NSPC transplantation in CNS injury and disease
      models.

PMID- 29657092
TI  - The critical chemical and mechanical regulation of folic acid on neural
      engineering.
AB  - The mandate of folic acid supplementation in grained products has reduced the
      occurrence of neural tube defects by one third in the U.S since its introduction
      by the Food and Drug Administration in 1998. However, the advantages and possible
      mechanisms of action of using folic acid for peripheral nerve engineering and
      neurological diseases still remain largely elusive. Herein, folic acid is
      described as an inexpensive and multifunctional niche component that modulates
      behaviors in different cells in the nervous system. The multiple benefits of
      modulation include: 1) generating chemotactic responses on glial cells, 2)
      inducing neurotrophin release, and 3) stimulating neuronal differentiation of a
      PC-12 cell system. For the first time, folic acid is also shown to enhance
      cellular force generation and global methylation in the PC-12 cells, thereby
      enabling both biomechanical and biochemical pathways to regulate neuron
      differentiation. These findings are evaluated in vivo for clinical translation.
      Our results suggest that folic acid-nerve guidance conduits may offer significant
      benefits as a low-cost, off-the-shelf product for reaching the functional
      recovery seen with autografts in large sciatic nerve defects. Consequently, folic
      acid holds great potential as a critical and convenient therapeutic intervention
      for neural engineering, regenerative medicine, medical prosthetics, and drug
      delivery.

PMID- 29657094
TI  - Advancing towards precision medicine in ARDS.

PMID- 29657093
TI  - Advances in transformable drug delivery systems.
AB  - These years, transformable drug delivery systems (DDSs), which hold the
      capability of changing formulation morphology and subsequent functionality at the
      desired disease site, have shown great promise in control of spatio-temporal drug
      delivery/release manner and enhanced treatment efficacy. Equipped with
      controllability and design flexibility, the transformable DDSs are being
      increasingly pursued for the development of precision drug delivery platforms for
      biomedical applications. In this review, we describe the recently developed
      intracelluarly and extracellularly transformable DDSs, especially associated with
      assembly or disassociation of the original formulation units, for achieving
      various functionalities, including prolonged retention time, inhibited
      endocytosis and enhanced cytotoxicity. Furthermore, the different stimuli, such
      as pH, enzyme, light, temperature, redox and mechanical force that trigger the
      transformation process are also introduced. The future outlook and challenges are
      discussed in the end.

PMID- 29657095
TI  - Epidemiology of bus fires in mainland China from 2006 to 2015.
AB  - OBJECTIVE: This study analyses the epidemiological characteristics of bus fires
      in mainland China over the past 10 years to develop prevention strategies and
      emergency procedures for such incidence and the resulting casualties. METHODS: We
      collected reports on bus fires from the media and news websites and looked up on
      Medline, PubMed, and Chinese National Knowledge Infrastructure databases for
      relevant publications in English or Chinese from January 1, 2006 to December 31,
      2015. RESULTS: In the past 10 years, there were 382 bus fires in mainland China.
      The frequency of fires was markedly higher in 2013 and 2014. The vast majority
      (89.1%) of the fires were caused by spontaneous combustion, followed by arson
      (5.0%). There were reports of casualties in 41 (10.7%) of the bus fires,
      including 144 deaths and 567 injuries. The fires leading to casualties resulted
      from spontaneous combustion in 22 (53.7%) incidents, arson in 12 (29.3%)
      incidents, and traffic accidents in 7 (17.1%) incidents. Arson caused the most
      casualties, including 91 deaths and 323 injuries. CONCLUSIONS: This
      epidemiological study presents characteristic findings related to bus fires in
      China mainland. The general trend of bus fires showed a gradual increase but with
      a fluctuation in several years. The regional distribution of bus fires revealed
      some specific characteristics, and most of bus fires happened in those regions
      locating in the eastern area of China mainland. The largest number of bus fires
      were caused by spontaneous combustion. Bus fires caused by arson accounting for
      only 5% of the total bus fires resulted in the most severe casualties. Most of
      bus arson occurred in the morning and evening rush hours.

PMID- 29657096
TI  - Mother, father and child traumatic stress reactions after paediatric burn: Within
      family co-occurrence and parent-child discrepancies in appraisals of child
      stress.
AB  - AIM: The current study examined occurrence and within-family associations of
      traumatic stress reactions after child burn injury, while in the same model
      addressing the role of parents' own symptoms in their reports of child symptoms.
      METHODS: One-hundred children (8-18 years old), and their mothers (n=90) and
      fathers (n=74) were assessed within the first month (T1) and three months (T2)
      after burn. Parents and children rated child traumatic stress reactions on the
      Children's Responses to Trauma Inventory (CRTI) and parents rated their own
      reactions on the Impact of Event Scale (IES). Cross-sectional associations at the
      two occasions were examined using a structural equation model. RESULTS:
      Occurrence of traumatic stress symptoms in the clinical range was higher in
      parents (T1: 24-50%; T2: 14-31%) than children (T1: 0-11%; T2: 3-5%, depending on
      whether children, mothers or fathers reported on symptoms). Traumatic stress
      symptoms of mothers at T1 and of both parents at T2 were significantly related to
      child self-reported symptoms. Moreover, mothers who experienced higher stress
      symptoms themselves gave higher ratings of their child's symptoms at both time
      points, while for fathers, this was only found at T2. CONCLUSIONS: The current
      study demonstrates the impact of pediatric burn injury on the family level, and
      shows simultaneous existence of within-family interrelatedness of traumatic
      stress and an influence of parents' own symptoms on their perception of child
      symptoms. Findings highlight the need for trauma symptom screening in all family
      members and for considering informants' symptoms to understand the child's
      functioning in particular.

PMID- 29657097
TI  - Single-Cell Transcriptomic Profiling of Pluripotent Stem Cell-Derived SCGB3A2+
      Airway Epithelium.
AB  - Lung epithelial lineages have been difficult to maintain in pure form in vitro,
      and lineage-specific reporters have proven invaluable for monitoring their
      emergence from cultured pluripotent stem cells (PSCs). However, reporter
      constructs for tracking proximal airway lineages generated from PSCs have not
      been previously available, limiting the characterization of these cells. Here, we
      engineer mouse and human PSC lines carrying airway secretory lineage reporters
      that facilitate the tracking, purification, and profiling of this lung subtype.
      Through bulk and single-cell-based global transcriptomic profiling, we find PSC
      derived airway secretory cells are susceptible to phenotypic plasticity
      exemplified by the tendency to co-express both a proximal airway secretory
      program as well as an alveolar type 2 cell program, which can be minimized by
      inhibiting endogenous Wnt signaling. Our results provide global profiles of
      engineered lung cell fates, a guide for improving their directed differentiation,
      and a human model of the developing airway.

PMID- 29657098
TI  - Inflammatory Responses and Barrier Function of Endothelial Cells Derived from
      Human Induced Pluripotent Stem Cells.
AB  - Several studies have reported endothelial cell (EC) derivation from human induced
      pluripotent stem cells (hiPSCs). However, few have explored their functional
      properties in depth with respect to line-to-line and batch-to-batch variability
      and how they relate to primary ECs. We therefore carried out accurate
      characterization of hiPSC-derived ECs (hiPSC-ECs) from multiple (non-integrating)
      hiPSC lines and compared them with primary ECs in various functional assays,
      which included barrier function using real-time impedance spectroscopy with an
      integrated assay of electric wound healing, endothelia-leukocyte interaction
      under physiological flow to mimic inflammation and angiogenic responses in in
      vitro and in vivo assays. Overall, we found many similarities but also some
      important differences between hiPSC-derived and primary ECs. Assessment of
      vasculogenic responses in vivo showed little difference between primary ECs and
      hiPSC-ECs with regard to functional blood vessel formation, which may be
      important in future regenerative medicine applications requiring vascularization.

PMID- 29657099
TI  - Design, synthesis and biological evaluation of novel 4-phenylisoquinolinone BET
      bromodomain inhibitors.
AB  - The bromodomain and extra-terminal (BET) family of epigenetic proteins has
      attracted considerable attention in drug discovery given its involvement in
      regulating gene transcription. Screening a focused small molecule library based
      on the bromodomain pharmacophore resulted in the identification of 2
      methylisoquinoline-1-one as a novel BET bromodomain-binding motif. Structure
      guided SAR exploration resulted in >10,000-fold potency improvement for the BRD4
      BD1 bromodomain. Lead compounds exhibited excellent potencies in both biochemical
      and cellular assays in MYC-dependent cell lines. Compound 36 demonstrated good
      physicochemical properties and promising exposure levels in exploratory PK
      studies.

PMID- 29657100
TI  - Synthesis of 1,2,4-triazole-linked urea/thiourea conjugates as cytotoxic and
      apoptosis inducing agents.
AB  - A new series of 1,2,4-triazole-linked urea and thiourea conjugates have been
      synthesized and evaluated for their in vitro cytotoxicity against selected human
      cancer cell lines namely, breast (MCF-7, MDA-MB-231), lung (A549) prostate
      (DU145) and one mouse melanoma (B16-F10) cell line and compared with reference
      drug. The compound 5t showed significant cytotoxicity on MCF-7 breast cancer cell
      line with a IC50 value of 7.22 +/- 0.47 uM among all the tested compounds.
      Notably, induction of apoptosis by compound 5t on MCF-7 cells was evaluated using
      different staining techniques such as acridine orange/ethidium bromide (AO/EB),
      annexin V-FITC/PI, and DAPI. Further, clonogenic assay indicates the inhibition
      of colony formation on MCF-7 cells by compound 5t. Moreover, the flow-cytometric
      analysis also revealed that compound 5t caused the arrest of cells at G0/G1 phase
      of cell cycle. In addition, the compounds when tested on normal human cells (L
      132) were found to be safer with low cytotoxicity profile.

PMID- 29657101
TI  - Novel 5-methyl-2-phenylphenanthridium derivatives as FtsZ-targeting antibacterial
      agents from structural simplification of natural product sanguinarine.
AB  - A novel series of 5-methyl-2-phenylphenanthridium derivatives were displayed
      outstanding activity against a panel of antibiotic-sensitive and -resistant
      bacteria strains compared with their precursor sanguinarine, ciprofloxacin and
      oxacillin sodium. Compounds 7 l, 7m and 7n were found to display the most
      effective activity against five sensitive strains (0.06-2 MUg/mL) and three
      resistant strains (0.25-4 MUg/mL). The kinetic profiles indicated that compound
      7l possessed the strongest bactericidal effect on S. aureus ATCC25923, with the
      MBC value of 16 MUg/mL. The cell morphology and the FtsZ polymerization assays
      indicated that these compounds inhibited the bacterial proliferation by
      interfering the function of bacterial FtsZ. The SARs showed that all the 4-methyl
      substituted 5-methyl-2-phenylphenanthridium subseries could be further
      investigated as the FtsZ-targeting antibacterial agents.

PMID- 29657102
TI  - Agonists of the gamma-aminobutyric acid type B (GABAB) receptor derived from beta
      hydroxy and beta-amino difluoromethyl ketones.
AB  - beta-Hydroxy difluoromethyl ketones represent the newest class of agonists of the
      GABA-B receptor, and they are structurally distinct from all other known agonists
      at this receptor because they do not display the carboxylic acid or amino group
      of gamma-aminobutyric acid (GABA). In this report, the design, synthesis, and
      biological evaluation of additional analogues of beta-hydroxy difluoromethyl
      ketones characterized the critical nature of the substituted aromatic group on
      the lead compound. The importance of these new data is interpreted by docking
      studies using the X-ray structure of the GABA-B receptor. Moreover, we also
      report that the synthesis and biological evaluation of beta-amino difluoromethyl
      ketones provided the most potent compound across these two series.

PMID- 29657103
TI  - Evaluation of simultaneous binding of Chromomycin A3 to the multiple sites of DNA
      by the new restriction enzyme assay.
AB  - Chromomycin A3 (CMA3) is an aureolic acid-type antitumor antibiotic. CMA3 forms
      dimeric complexes with divalent cations, such as Mg2+, which strongly binds to
      the GC rich sequence of DNA to inhibit DNA replication and transcription. In this
      study, the binding property of CMA3 to the DNA sequence containing multiple GC
      rich binding sites was investigated by measuring the protection from hydrolysis
      by the restriction enzymes, AccII and Fnu4HI, for the center of the CGCG site and
      the 5'-GC?GGC site, respectively. In contrast to the standard DNase I
      footprinting method, the DNA substrates are fully hydrolyzed by the restriction
      enzymes, therefore, the full protection of DNA at all the cleavable sites
      indicates that CMA3 simultaneously binds to all the binding sites. The
      restriction enzyme assay has suggested that CMA3 has a high tendency to bind the
      successive CGCG sites and the CGG repeat.

PMID- 29657104
TI  - Inhibitory effects of methyl-3,5-di-O-caffeoyl-epi-quinate on RANKL-induced
      osteoclast differentiation.
AB  - In this study, we have shown that methyl-3,5-di-O-caffeoyl-epi-quinate, a
      naturally occurring compound isolated from Ainsliaea acerifolia, inhibits
      receptor activator of nuclear factor-kappaB ligand (RANKL)-induced formation of
      multinucleated tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts
      and the expression of osteoclast marker genes. Methyl-3,5-di-O-caffeoyl-epi
      quinate also inhibited RANKL-induced activation of p38, Akt and extracellular
      signal-regulated kinase (ERK) as well as the expression of nuclear factor of
      activated T-cell (NFATc1), the key regulator of osteoclast differentiation.
      Negative regulators for osteoclast differentiation was upregulated by methyl-3,5
      di-O-caffeoyl-epi-quinate. Collectively, our results suggested that methyl-3,5-di
      O-caffeoyl-epi-quinate suppresses osteoclast differentiation via downregulation
      of RANK signaling pathways and NFATc1.

PMID- 29657105
TI  - Initial stability of a highly porous titanium cup in an acetabular bone defect
      model.
AB  - BACKGROUNDS: The purpose of this study was to quantify the initial stability of a
      highly porous titanium cup using an acetabular bone defect model. METHODS: The
      maximum torque of a highly porous titanium cup, with a pore size of 640 MUm and
      porosity of 60%, was measured using rotational and lever-out torque testing and
      compared to that of a titanium-sprayed cup. The bone models were prepared using a
      polyurethane foam block and had three levels of bone coverage: 100, 70, and 50%.
      RESULTS: The highly porous titanium cup demonstrated significantly higher maximum
      torque than the titanium-sprayed cups in the three levels of bone defects. On
      rotational torque testing, it was found to be 1.5, 1.3, and 1.3 times stronger
      than the titanium-sprayed cups with 100, 70 and 50% bone coverage, respectively.
      Furthermore, it was found to be 2.2, 2.3, and 1.5 times stronger on lever-out
      testing than the titanium-sprayed cup. No breakage in the porous layers was noted
      during the testing. CONCLUSION: This study provides additional evidence of the
      initial stability of highly porous titanium cup, even in the presence of
      acetabular bone defects.

PMID- 29657106
TI  - Hyponatraemia is independently associated with in-hospital mortality in patients
      with pneumonia.
AB  - BACKGROUND: Hyponatraemia on hospital admission has been shown to be a risk
      factor for illness severity in critically ill patients. The aim of the present
      study was to investigate whether hyponatraemia on emergency department (ED)
      admission independently influences in-hospital mortality, ICU admission, and/or
      length of hospitalisation in patients with pneumonia. METHODS: 610 patients
      (64.4% male, median 66 years) diagnosed with pneumonia were identified by
      retrospective screening of electronic admission data (06/2011-06/2013). Patients
      were admitted to the ED of Bern University Hospital, Switzerland. Patient
      characteristics, potential confounders, and patient-centred clinical outcomes,
      including mortality, ICU admission, and length of hospitalisation, were analysed.
      Multivariate logistic analysis adjusted for typical confounders was performed to
      analyse the association of hyponatraemia with clinical outcomes. RESULTS: In a
      large cohort of consecutive acutely admitted patients with pneumonia, the overall
      in-hospital mortality rate was 12.5%; 21.2% of patients required primary or
      secondary ICU admission, and the median length of hospital stay was 8 (IQR 5-13)
      days. At baseline, 47 patients (7.7%) were found to have concomitant
      hyponatraemia. Multivariate regression revealed a significant association between
      hyponatraemia and in-hospital mortality (adjusted OR: 2.7, 95% CI: 1.3-5.9, p =
      0.010), but not with ICU admission (adjusted OR: 1.8, 95% CI: 0.9-3.6, p = 0.103)
      or length of hospitalisation (p = 0.493) after adjustment for age, neoplasia,
      COPD, suspected sepsis, and cardiac disease. The association was robust if
      controlled for other covariates, e.g. CRB-65 score. CONCLUSIONS: Hyponatraemia on
      admission predicts poor outcome and is an independent risk factor for in-hospital
      mortality in admitted patients diagnosed with pneumonia.

PMID- 29657107
TI  - Cardiovascular implications of Zika virus infection.

PMID- 29657109
TI  - Relevance of the GOLD 2017 recommendations in habitual clinical practice.

PMID- 29657110
TI  - Symbiotic relationship between hydrothermal carbonization technology and
      anaerobic digestion for food waste in China.
AB  - Food waste (FW) is traditionally disposed through landfills and incineration in
      China. Nowadays, there are some promising methods, such as anaerobic digestion
      (AD) or feeding and composting, which are being applied in pilot cities. However,
      the inherent characteristics of Chinese FW may be regarded as a double-edged
      sword in the practical applications of these disposal methods. To overcome these
      challenges, two modes of the hydrothermal carbonization (HTC) process were
      reviewed as innovative strategies in this article. Meanwhile, the "symbiotic
      relationship" between Chinese FW and HTC technologies was highlighted. To improve
      treatment efficiency of FW, we should not only try different methods and develop
      existing technologies, but also pay more attention to the utilization and "1 + 1
      > 2" synergistic effect of their combinations, such as the combination of HTC and
      AD as a co-treatment method for saving on the construction cost and avoiding
      redistribution of social resources.

PMID- 29657111
TI  - Nudging in screening: Literature review and ethical guidance.
AB  - OBJECTIVES: Nudging is the purposeful alteration of choices presented to people
      that aims to make them choose in predicted ways. While nudging has been used to
      assure high uptake and good outcome of screening programs, it has been criticized
      for being paternalistic, undermining free choice, and shared decision making.
      Accordingly, the objective of this study is to explore a) nudging strategies
      identified in screening, b) arguments for and against nudging; and on basis of
      this, to c) suggest a tentative conclusion on how to handle nudging in screening.
      METHODS: Literature searches in Ovid MEDLINE and PsycINFO for combinations of
      screening and nudging. Screening based on content analysis of titles, abstracts,
      and articles. RESULTS: 239 references were identified and 109 were included.
      Several forms of nudging were identified: framed information, default bias, or
      authority bias. Uptake and public health outcome were the most important goals.
      Arguments for nudging were bounded rationality, unavoidability, and beneficence,
      while lack of transparency, crowding out of intrinsic values, and paternalism
      were arguments against it. The analysis indicates that nudging can be acceptable
      for screenings with (high quality) evidence for high benefit-harm ratio
      (beneficence), where nudging does not infringe other ethical principles, such as
      justice and non-maleficence. In particular, nudging should not only focus on
      attendance rates, but also on making people "better choosers." PRACTICE
      IMPLICATIONS: Four specific recommendations follow from the review and the
      analysis: 1) Nudging should be addressed in an explicit and transparent manner.
      2) The means of nudging have to be in proportion to the benefit-harm ratio. 3)
      Disagreement on the evidence for either benefits or harms warrants special care.
      4) Assessing and assuring the intended outcome of nudging appears to be crucial,
      as it can be context dependent.

PMID- 29657108
TI  - Use of oral anticoagulant drugs in older patients with atrial fibrillation in
      internal medicine wards.

PMID- 29657112
TI  - High expression of CPT1b in skeletal muscle in metabolically healthy older
      subjects.
AB  - AIM: Ageing is often associated with metabolic abnormalities such as insulin
      resistance, although some people remain metabolically healthy throughout their
      lives. The aim of this study was to gain more insight into metabolic health with
      increasing age. METHODS: Two groups of robust and of frail subjects,
      respectively, were identified based on a composite ageing indicator and recruited
      from the French SU.VI.MAX 2 cohort of older disease-free subjects. In all, 14 men
      and 12 women, aged 67+/-4 years, with similar anthropometric and metabolic
      characteristics at baseline (BMI: 24.5+/-2.9kg.m-2) were included in the
      Compaliclamp study. Skeletal muscle biopsy was performed to assess expression of
      a set of metabolic and sirtuin (SIRT) genes. Also, whole-body substrate oxidation
      and insulin sensitivity were determined using the euglycaemic-hyperinsulinaemic
      clamp and indirect calorimetry techniques. RESULTS: Robust subjects were more
      insulin-sensitive, oxidized more lipid in a fasting state and stored more glucose
      during the euglycaemic - hyperinsulinaemic clamp than did frail subjects. At the
      gene-expression level in skeletal muscle, carnitine palmitoyltransferase 1b
      (CPT1b) messenger RNA (mRNA) levels were around four times higher in the robust
      compared with frail counterparts. Moreover, both SIRT2 and SIRT6 expression was
      lower in robust subjects and correlated with CPT1b expression. CONCLUSION: CPT1b
      overexpression could be helping to maintain metabolic health with increasing age.
      Thus, it is suggested that targeting CPT1b expression might be an interesting
      strategy to counteract frailty at an early stage. In addition, future studies
      should examine the role of sirtuin in CPT1b expression regulation.

PMID- 29657113
TI  - Strategic Acoustic Control of a Hummingbird Courtship Dive.
AB  - Male hummingbirds court females with a high-speed dive in which they "sing" with
      their tail feathers. The male's choice of trajectory provides him strategic
      control over acoustic frequency and pressure levels heard by the female. Unlike
      related species, male Costa's hummingbirds (Calypte costae) choose to place their
      dives to the side of females. Here we show that this minimizes an audible Doppler
      curve in their dive sound, thereby depriving females of an acoustic indicator
      that would otherwise reveal male dive speed. Wind-tunnel experiments indicate
      that the sounds produced by their feathers are directional; thus, males should
      aim their tail toward females. High-speed video of dives reveal that males twist
      half of their tail vertically during the dive, which acoustic-camera video shows
      effectively aims this sound sideways, toward the female. Our results demonstrate
      that male animals can strategically modulate female perception of dynamic aspects
      of athletic motor displays, such as their speed.

PMID- 29657114
TI  - Augmin Antagonizes Katanin at Microtubule Crossovers to Control the Dynamic
      Organization of Plant Cortical Arrays.
AB  - Plant cells do not possess centrosomes, which serve as the microtubule organizing
      center in animal cells; how plant cell microtubule arrays are established and
      maintain their dynamics remain poorly understood [1]. The gamma-tubulin complex
      and the katanin complex play central roles in the organization of plant cortical
      microtubules [2-6]. Previously, we reported that the augmin complex recruits the
      gamma-tubulin complex to preexisting microtubules and initiates microtubule
      nucleation [7]. Moreover, we described how an intricate interaction between the
      katanin p60 subunit KTN1 and the p80 subunit KTN80 confers precise microtubule
      severing at either microtubule branching nucleation sites or crossovers [8].
      Here, we observed that augmin preferentially localizes to microtubule crossovers.
      Live-cell observations and analyses revealed that, whereas a small portion of
      crossover-localized augmin complexes act to trigger nascent microtubule
      nucleation, the majority function in stabilizing the architecture of microtubule
      crossovers. Finally, genetic analyses and computational modeling confirmed that
      suppression of augmin activity elevates microtubule severing frequency and
      facilitates the formation of aligned microtubule arrays. Combined, our findings
      reveal an unexpected role of augmin and demonstrate that augmin antagonizes
      katanin-mediated microtubule severing. Furthermore, we propose a novel mechanism
      for how augmin determines self-organization of plant cortical microtubules by
      preventing microtubule severing at crossovers in addition to triggering
      microtubule nucleation.

PMID- 29657115
TI  - Novelty-Sensitive Dopaminergic Neurons in the Human Substantia Nigra Predict
      Success of Declarative Memory Formation.
AB  - The encoding of information into long-term declarative memory is facilitated by
      dopamine. This process depends on hippocampal novelty signals, but it remains
      unknown how midbrain dopaminergic neurons are modulated by declarative-memory
      based information. We recorded individual substantia nigra (SN) neurons and
      cortical field potentials in human patients performing a recognition memory task.
      We found that 25% of SN neurons were modulated by stimulus novelty. Extracellular
      waveform shape and anatomical location indicated that these memory-selective
      neurons were putatively dopaminergic. The responses of memory-selective neurons
      appeared 527 ms after stimulus onset, changed after a single trial, and were
      indicative of recognition accuracy. SN neurons phase locked to frontal cortical
      theta-frequency oscillations, and the extent of this coordination predicted
      successful memory formation. These data reveal that dopaminergic neurons in the
      human SN are modulated by memory signals and demonstrate a progression of
      information flow in the hippocampal-basal ganglia-frontal cortex loop for memory
      encoding.

PMID- 29657117
TI  - Evidence that Magnetic Navigation and Geomagnetic Imprinting Shape Spatial
      Genetic Variation in Sea Turtles.
AB  - The canonical drivers of population genetic structure, or spatial genetic
      variation, are isolation by distance and isolation by environment. Isolation by
      distance predicts that neighboring populations will be genetically similar and
      geographically distant populations will be genetically distinct [1]. Numerous
      examples also exist of isolation by environment, a phenomenon in which
      populations that inhabit similar environments (e.g., same elevation, temperature,
      or vegetation) are genetically similar even if they are distant, whereas
      populations that inhabit different environments are genetically distinct even
      when geographically close [2-4]. These dual models provide a widely accepted
      conceptual framework for understanding population structure [5-8]. Here, we
      present evidence for an additional, novel process that we call isolation by
      navigation, in which the navigational mechanism used by a long-distance migrant
      influences population structure independently of isolation by either distance or
      environment. Specifically, we investigated the population structure of loggerhead
      sea turtles (Caretta caretta) [9], which return to nest on their natal beaches by
      seeking out unique magnetic signatures along the coast-a behavior known as
      geomagnetic imprinting [10-12]. Results reveal that spatial variation in Earth's
      magnetic field strongly predicts genetic differentiation between nesting beaches,
      even when environmental similarities and geographic proximity are taken into
      account. The findings provide genetic corroboration of geomagnetic imprinting
      [10, 13]. Moreover, they provide strong evidence that geomagnetic imprinting and
      magnetic navigation help shape the population structure of sea turtles and
      perhaps numerous other long-distance migrants that return to their natal areas to
      reproduce [13-17].

PMID- 29657116
TI  - Gaze and the Control of Foot Placement When Walking in Natural Terrain.
AB  - Human locomotion through natural environments requires precise coordination
      between the biomechanics of the bipedal gait cycle and the eye movements that
      gather the information needed to guide foot placement. However, little is known
      about how the visual and locomotor systems work together to support movement
      through the world. We developed a system to simultaneously record gaze and full
      body kinematics during locomotion over different outdoor terrains. We found that
      not only do walkers tune their gaze behavior to the specific information needed
      to traverse paths of varying complexity but that they do so while maintaining a
      constant temporal look-ahead window across all terrains. This strategy allows
      walkers to use gaze to tailor their energetically optimal preferred gait cycle to
      the upcoming path in order to balance between the drive to move efficiently and
      the need to place the feet in stable locations. Eye movements and locomotion are
      intimately linked in a way that reflects the integration of energetic costs,
      environmental uncertainty, and momentary informational demands of the locomotor
      task. Thus, the relationship between gaze and gait reveals the structure of the
      sensorimotor decisions that support successful performance in the face of the
      varying demands of the natural world. VIDEO ABSTRACT.

PMID- 29657118
TI  - Functional Maps of Mechanosensory Features in the Drosophila Brain.
AB  - Johnston's organ is the largest mechanosensory organ in Drosophila. It
      contributes to hearing, touch, vestibular sensing, proprioception, and wind
      sensing. In this study, we used in vivo 2-photon calcium imaging and unsupervised
      image segmentation to map the tuning properties of Johnston's organ neurons
      (JONs) at the site where their axons enter the brain. We then applied the same
      methodology to study two key brain regions that process signals from JONs: the
      antennal mechanosensory and motor center (AMMC) and the wedge, which is
      downstream of the AMMC. First, we identified a diversity of JON response types
      that tile frequency space and form a rough tonotopic map. Some JON response types
      are direction selective; others are specialized to encode amplitude modulations
      over a specific range (dynamic range fractionation). Next, we discovered that
      both the AMMC and the wedge contain a tonotopic map, with a significant increase
      in tonotopy-and a narrowing of frequency tuning-at the level of the wedge.
      Whereas the AMMC tonotopic map is unilateral, the wedge tonotopic map is
      bilateral. Finally, we identified a subregion of the AMMC/wedge that responds
      preferentially to the coherent rotation of the two mechanical organs in the same
      angular direction, indicative of oriented steady air flow (directional wind).
      Together, these maps reveal the broad organization of the primary and secondary
      mechanosensory regions of the brain. They provide a framework for future efforts
      to identify the specific cell types and mechanisms that underlie the hierarchical
      re-mapping of mechanosensory information in this system.

PMID- 29657119
TI  - Reconciling Conflicting Phylogenies in the Origin of Sweet Potato and Dispersal
      to Polynesia.
AB  - The sweet potato is one of the world's most widely consumed crops, yet its
      evolutionary history is poorly understood. In this paper, we present a
      comprehensive phylogenetic study of all species closely related to the sweet
      potato and address several questions pertaining to the sweet potato that remained
      unanswered. Our research combined genome skimming and target DNA capture to
      sequence whole chloroplasts and 605 single-copy nuclear regions from 199
      specimens representing the sweet potato and all of its crop wild relatives
      (CWRs). We present strongly supported nuclear and chloroplast phylogenies
      demonstrating that the sweet potato had an autopolyploid origin and that Ipomoea
      trifida is its closest relative, confirming that no other extant species were
      involved in its origin. Phylogenetic analysis of nuclear and chloroplast genomes
      shows conflicting topologies regarding the monophyly of the sweet potato. The
      process of chloroplast capture explains these conflicting patterns, showing that
      I. trifida had a dual role in the origin of the sweet potato, first as its
      progenitor and second as the species with which the sweet potato introgressed so
      one of its lineages could capture an I. trifida chloroplast. In addition, we
      provide evidence that the sweet potato was present in Polynesia in pre-human
      times. This, together with several other examples of long-distance dispersal in
      Ipomoea, negates the need to invoke ancient human-mediated transport as an
      explanation for its presence in Polynesia. These results have important
      implications for understanding the origin and evolution of a major global food
      crop and question the existence of pre-Columbian contacts between Polynesia and
      the American continent.

PMID- 29657120
TI  - Breast lymphoma occurring after an invasive ductal breast carcinoma developed in
      the same area: A case report and literature review.
AB  - Chemo- and radiotherapy are treatments very helpful to cure cancers but are also
      well known for adverse effects such as secondary cancers. Breast cancers
      following Hodgkin lymphoma have been relatively well studied. Breast cancers
      after radiotherapy covering or nearby breasts or nipples are usually carcinomas
      or secondary sarcomas. Among the big cohort of patients treated for breast
      carcinomas, breast lymphomas developed in the same area are not usual.
      Nevertheless, published studies described a significant increased risk of non
      Hodgkin lymphoma after initial radiotherapy for a solid cancer. Here, we report a
      case of a secondary breast lymphoma observed in a 53-year-old woman treated 13
      years before for a ductal carcinoma and analyse such second tumors with a review
      of the literature. This case report emphasizes the importance of the biopsy in
      case of recurrence in breast cancer to give the appropriate treatment.

PMID- 29657121
TI  - The experimental determination of DNA energetics: Comment on "DNA melting and
      energetics of the double helix" by Alexander Vologodskii and Maxim D. Frank
      Kamenetskii.

PMID- 29657122
TI  - Silent Cardiac Haemangioma of Left Ventricle Coexisting with Vertebral
      Haemangioma: Diagnosis by Cardiac Magnetic Resonance Imaging.

PMID- 29657123
TI  - Transcriptome of the bivalve Limecola balthica L. from Western Pacific: A new
      resource for studies of European populations.
AB  - The Baltic clam Limecola balthica L. (Tellinidae) is broadly used in
      ecophysiological, toxicological, evolutionary and environmental monitoring
      studies. However, it is poorly studied in respect of genome and gene functions.
      We obtained a transcriptome of Limecola b. balthica from Kamchatka (Western
      Pacific) generated with the use of Illumina high-throughput sequencing. We
      annotated 11,374 proteins, including 53 from the oxidative phosphorylation
      pathway and a number of pollution-stress biomarkers, recovered 254,540 single
      nucleotide variants within two annotated transcriptomes including 25,330 scorable
      in the previously published European data. Our results confirmed the available
      allozyme data indicating that nuclear genomes of the clams from the Baltic Sea
      were intermediate in their genetic composition between the Pacific (L. b.
      balthica) and the Atlantic (L. b. rubra) subspecies. At the same time, the
      mitochondrial genomes of Limecola from Kamchatka were nearly identical to the
      single published genome from the Baltic. The genomic diversity in Limecola was
      found to be high and comparable with that of other marine mollusks (0.0138 and
      0.0142 heterozygous positions in the two studied transcriptomes). The data
      obtained in our study are a valuable resource for further development of genomic
      markers for evolutionary genetic and ecophysiological studies of L. balthica
      complex.

PMID- 29657124
TI  - Dynamic bacterial community changes in the autothermal thermophilic aerobic
      digestion process with cell lysis activities, shaking and temperature increase.
AB  - Autothermal thermophilic aerobic digestion (ATAD) is conducted for stabilization
      of sludge waste and is driven by the action of various microorganisms under
      aerobic conditions. However, the mechanism controlling bacterial community
      changes during ATAD via three (initial, middle and final) phases is currently
      unclear. To investigate this mechanism, activity analysis and a microcosm assay
      with shaking were performed on a bacterial community during the initial, middle,
      and final phases of incubation. Cell lysis activities toward gram-negative
      bacteria, but not gram-positive bacteria, were detected in the ATAD samples in
      the middle and final phases. During shaking incubation in initial-phase samples
      at 30  degrees C, major operational taxonomic units (OTUs) related to
      Acinetobacter indicus and Arcobacter cibarius dramatically increased along with
      decreases in several major OTUs. In middle-phase samples at 45  degrees C, we
      observed a major alteration of OTUs related to Caldicellulosiruptor bescii and
      Aciditerrimonas ferrireducens, together with distinct decreases in several other
      OTUs. Final-phase samples maintained a stable bacterial community with major OTUs
      showing limited similarities to Heliorestis baculata, Caldicellulosiruptor
      bescii, and Ornatilinea apprima. In conclusion, the changes in the bacterial
      community observed during ATAD could be partially attributed to the cell lysis
      activity toward gram-negative bacteria in the middle and final phases. The
      microcosm assay suggested that certain physical factors, such as a high oxygen
      supply and shearing forces, also might contribute to bacterial community changes
      in the initial and middle phases, and to the stable bacterial community in the
      final phase of ATAD.

PMID- 29657125
TI  - Rice straw pretreatment using deep eutectic solvents with different constituents
      molar ratios: Biomass fractionation, polysaccharides enzymatic digestion and
      solvent reuse.
AB  - Lignocellulosic biomass pretreatment with deep eutectic solvents (DESs) is a
      promising and challenging process for production of biofuels and valuable
      platform chemicals. In this work, rice straw was mainly fractionated into
      carbohydrate-rich materials (CRMs) and lignin-rich materials (LRMs) by 90% lactic
      acid/choline chloride (LC)-water solution with different molar ratio of hydrogen
      bond donor (HBD, lactic acid) and hydrogen bond acceptor (HBA, choline chloride).
      It was found that high HBD/HBA molar ratio of DESs was favorable for achieving
      CRMs and LRMs with high purity, and both HBD and HBA were responsible for
      effective biomass fractionation possibly due to their synergistic effect on
      highly efficient breakage of the linkage between hemicellulose and lignin and
      thus lignin extraction. About 30%-35% of lignin in native rice straw was
      fractionated as LRMs, and exceeding 70% of xylan were removed and fractionated
      into the liquid stream as forms of xylose, furfural and humins after pretreatment
      using aqueous LC (3:1, 5:1) solution. Consequently, polysaccharides enzymatic
      hydrolysis of the CRMs were significantly enhanced. Moreover, all the DESs could
      be recovered with high yields of around 90%, and 69% of the LC (3:1) was
      recovered after 5 cycles reuse at 90  degrees C. Besides, the recycled DES
      maintained a good pretreatment ability, and glucose yields of 60-70% were
      achieved in the enzymatic hydrolysis of CRMs obtained in each cycle. The facile
      process established in present work is promising for large scale production of
      fermentable sugars and other chemicals.

PMID- 29657126
TI  - Xylosylation of proteins by expression of human xylosyltransferase 2 in plants.
AB  - Through the years, the post-translational modification of plant-made recombinant
      proteins has been a considerable problem. Protein glycosylation is arguably the
      most important post-translational modification; thus, for the humanization of
      protein glycosylation in plants, the introduction, repression, and knockout of
      many glycosylation-related genes has been carried out. In addition, plants lack
      mammalian-type protein O-glycosylation pathways; thus, for the synthesis of
      mammalian O-glycans in plants, the construction of these pathways is necessary.
      In this study, we successfully xylosylated the recombinant human proteoglycan
      core protein, serglycin, by transient expression of human xylosyltransferase 2 in
      Nicotiana benthamiana plants. When human serglycin was co-expressed with human
      xylosyltransferase 2 in plants, multiple serine residues of eight xylosylation
      candidates were xylosylated. From the results of carbohydrate assays for total
      soluble proteins, some endogenous plant proteins also appeared to be xylosylated,
      likely through the actions of xylosyltransferase 2. The xylosylation of core
      proteins is the initial step of the glycosaminoglycan part of the synthesis of
      proteoglycans. In the future, these novel findings may lead to whole mammalian
      proteoglycan synthesis in plants.

PMID- 29657127
TI  - The Intestinal Microbiota in Colorectal Cancer.
AB  - Experimental evidence from the past years highlights a key role for the
      intestinal microbiota in inflammatory and malignant gastrointestinal diseases.
      Diet exhibits a strong impact on microbial composition and provides risk for
      developing colorectal carcinoma (CRC). Large metagenomic studies in human CRC
      associated microbiome signatures with the colorectal adenoma-carcinoma sequence,
      suggesting a fundamental role of the intestinal microbiota in the evolution of
      gastrointestinal malignancy. Basic science established a critical function for
      the intestinal microbiota in promoting tumorigenesis. Further studies are needed
      to decipher the mechanisms of tumor promotion and microbial co-evolution in CRC,
      which may be exploited therapeutically in the future.

PMID- 29657128
TI  - Genomic Features of Response to Combination Immunotherapy in Patients with
      Advanced Non-Small-Cell Lung Cancer.
AB  - Combination immune checkpoint blockade has demonstrated promising benefit in lung
      cancer, but predictors of response to combination therapy are unknown. Using
      whole-exome sequencing to examine non-small-cell lung cancer (NSCLC) treated with
      PD-1 plus CTLA-4 blockade, we found that high tumor mutation burden (TMB)
      predicted improved objective response, durable benefit, and progression-free
      survival. TMB was independent of PD-L1 expression and the strongest feature
      associated with efficacy in multivariable analysis. The low response rate in TMB
      low NSCLCs demonstrates that combination immunotherapy does not overcome the
      negative predictive impact of low TMB. This study demonstrates the association
      between TMB and benefit to combination immunotherapy in NSCLC. TMB should be
      incorporated in future trials examining PD-(L)1 with CTLA-4 blockade in NSCLC.

PMID- 29657131
TI  - Unusual Constriction Zones in the Major Porins OmpU and OmpT from Vibrio
      cholerae.
AB  - The outer membranes (OM) of many Gram-negative bacteria contain general porins,
      which form nonspecific, large-diameter channels for the diffusional uptake of
      small molecules required for cell growth and function. While the porins of
      Enterobacteriaceae (e.g., E. coli OmpF and OmpC) have been extensively
      characterized structurally and biochemically, much less is known about their
      counterparts in Vibrionaceae. Vibrio cholerae, the causative agent of cholera,
      has two major porins, OmpU and OmpT, for which no structural information is
      available despite their importance for the bacterium. Here we report high
      resolution X-ray crystal structures of V. cholerae OmpU and OmpT complemented
      with molecular dynamics simulations. While similar overall to other general
      porins, the channels of OmpU and OmpT have unusual constrictions that create
      narrower barriers for small-molecule permeation and change the internal electric
      fields of the channels. Together with electrophysiological and in vitro transport
      data, our results illuminate small-molecule uptake within the Vibrionaceae.

PMID- 29657129
TI  - Multi-stage Differentiation Defines Melanoma Subtypes with Differential
      Vulnerability to Drug-Induced Iron-Dependent Oxidative Stress.
AB  - Malignant transformation can result in melanoma cells that resemble different
      stages of their embryonic development. Our gene expression analysis of human
      melanoma cell lines and patient tumors revealed that melanoma follows a two
      dimensional differentiation trajectory that can be subclassified into four
      progressive subtypes. This differentiation model is associated with subtype
      specific sensitivity to iron-dependent oxidative stress and cell death known as
      ferroptosis. Receptor tyrosine kinase-mediated resistance to mitogen-activated
      protein kinase targeted therapies and activation of the inflammatory signaling
      associated with immune therapy involves transitions along this differentiation
      trajectory, which lead to increased sensitivity to ferroptosis. Therefore,
      ferroptosis-inducing drugs present an orthogonal therapeutic approach to target
      the differentiation plasticity of melanoma cells to increase the efficacy of
      targeted and immune therapies.

PMID- 29657132
TI  - Structure of Radical-Induced Cell Death1 Hub Domain Reveals a Common alphaalpha
      Scaffold for Disorder in Transcriptional Networks.
AB  - Communication within cells relies on a few protein nodes called hubs, which
      organize vast interactomes with many partners. Frequently, hub proteins are
      intrinsically disordered conferring multi-specificity and dynamic communication.
      Conversely, folded hub proteins may organize networks using disordered partners.
      In this work, the structure of the RST domain, a unique folded hub, is solved by
      nuclear magnetic resonance spectroscopy and small-angle X-ray scattering, and its
      complex with a region of the transcription factor DREB2A is provided through data
      driven HADDOCK modeling and mutagenesis analysis. The RST fold is unique, but
      similar structures are identified in the PAH (paired amphipathic helix), TAFH
      (TATA-box-associated factor homology), and NCBD (nuclear coactivator binding
      domain) domains. We designate them as a group the alphaalpha hubs, as they share
      an alphaalpha-hairpin super-secondary motif, which serves as an organizing
      platform for malleable helices of varying topology. This allows for partner
      adaptation, exclusion, and selection. Our findings provide valuable insights into
      structural features enabling signaling fidelity.

PMID- 29657134
TI  - Early mortality and morbidity following a type II odontoid fracture in the
      elderly.
AB  - BACKGROUND: We aimed to analyse the rates of early and causes of death in
      patients aged over 65 years with a type II odontoid fracture. METHODS: A
      consecutive series of 93 patients with a type II fracture of the odontoid process
      was retrospectively identified. Data collected included patient demographics, co
      morbidities, associated injuries, neurological injury, date of death and cause of
      death. Mean patient age was 81. Five patients (5%) were treated operatively while
      the rest were treated in a hard cervical collar. Five patients (5%) had an
      incomplete cervical cord injury secondary to the fracture. RESULTS: The rate of
      mortality at 30 days was 10% (9 patients) and at 90 days it was 16% (15
      patients). Following multivariate analysis, the factors found to significantly
      increase the risk of 30-day mortality included increasing age, increasing injury
      severity score and leukaemia. Following univariate analysis the only factor found
      to increase the risk of 90-day mortality was advancing age. The commonest causes
      of death were pneumonia and ischaemic coronary disease. CONCLUSION: Our results
      suggest that this patient cohort is frail and at risk of early mortality. We
      suggest that their inpatient care be provided in close conjunction with elderly
      care physicians.

PMID- 29657130
TI  - The Platelet Lifeline to Cancer: Challenges and Opportunities.
AB  - Besides their function in limiting blood loss and promoting wound healing,
      experimental evidence has highlighted platelets as active players in all steps of
      tumorigenesis including tumor growth, tumor cell extravasation, and metastasis.
      Additionally, thrombocytosis in cancer patients is associated with adverse
      patient survival. Due to the secretion of large amounts of microparticles and
      exosomes, platelets are well positioned to coordinate both local and distant
      tumor-host crosstalk. Here, we present a review of recent discoveries in the
      field of platelet biology and the role of platelets in cancer progression as well
      as challenges in targeting platelets for cancer treatment.

PMID- 29657133
TI  - Development of a Prototype System for Archiving Integrative/Hybrid Structure
      Models of Biological Macromolecules.
AB  - Essential processes in biology are carried out by large macromolecular
      assemblies, whose structures are often difficult to determine by traditional
      methods. Increasingly, researchers combine measured data and computed information
      from several complementary methods to obtain "hybrid" or "integrative" structural
      models of macromolecules and their assemblies. These integrative/hybrid (I/H)
      models are not archived in the PDB because of the absence of standard data
      representations and processing mechanisms. Here we present the development of
      data standards and a prototype system for archiving I/H models. The data
      standards provide the definitions required for representing I/H models that span
      multiple spatiotemporal scales and conformational states, as well as spatial
      restraints derived from different experimental techniques. Based on these data
      definitions, we have built a prototype system called PDB-Dev, which provides the
      infrastructure necessary to archive I/H structural models. PDB-Dev is now
      accepting structures and is open to the community for new submissions.

PMID- 29657136
TI  - BLU-667 Targets RET-Altered Cancers.
AB  - Findings from a phase I study indicate that the investigational RET inhibitor BLU
      667 is safe and well tolerated, inducing good responses in patients with RET
      altered medullary thyroid cancer or non-small cell lung cancer.

PMID- 29657137
TI  - Adjuvant Therapy for Melanoma Prolongs RFS.
AB  - The PD-1 inhibitor pembrolizumab may be an effective adjuvant therapy for
      patients with stage III melanoma. In a clinical trial, patients who received the
      drug had a 12-month recurrence-free survival rate of 75.4%, compared with 61% for
      patients who received a placebo.

PMID- 29657135
TI  - Precision Targeted Therapy with BLU-667 for RET-Driven Cancers.
AB  - The receptor tyrosine kinase rearranged during transfection (RET) is an oncogenic
      driver activated in multiple cancers, including non-small cell lung cancer
      (NSCLC), medullary thyroid cancer (MTC), and papillary thyroid cancer. No
      approved therapies have been designed to target RET; treatment has been limited
      to multikinase inhibitors (MKI), which can have significant off-target toxicities
      and limited efficacy. BLU-667 is a highly potent and selective RET inhibitor
      designed to overcome these limitations. In vitro, BLU-667 demonstrated >=10-fold
      increased potency over approved MKIs against oncogenic RET variants and
      resistance mutants. In vivo, BLU-667 potently inhibited growth of NSCLC and
      thyroid cancer xenografts driven by various RET mutations and fusions without
      inhibiting VEGFR2. In first-in-human testing, BLU-667 significantly inhibited RET
      signaling and induced durable clinical responses in patients with RET-altered
      NSCLC and MTC without notable off-target toxicity, providing clinical validation
      for selective RET targeting.Significance: Patients with RET-driven cancers derive
      limited benefit from available MKIs. BLU-667 is a potent and selective RET
      inhibitor that induces tumor regression in cancer models with RET mutations and
      fusions. BLU-667 attenuated RET signaling and produced durable clinical responses
      in patients with RET-altered tumors, clinically validating selective RET
      targeting. Cancer Discov; 8(7); 836-49. (c)2018 AACR.See related commentary by
      Iams and Lovly, p. 797This article is highlighted in the In This Issue feature,
      p. 781.

PMID- 29657138
TI  - NHS is harming patient confidentiality by sharing data for immigration purposes,
      say MPs.

PMID- 29657139
TI  - Power Doppler Ultrasound Evaluation of Peripheral Joint, Entheses, Tendon, and
      Bursa Abnormalities in Psoriatic Patients: A Clinical Study.
AB  - OBJECTIVE: To evaluate the prevalence rates of peripheral joint, enthesis,
      tendon, and bursa abnormalities by power Doppler (PD) ultrasonic examination in
      patients with psoriatic arthritis (PsA), psoriatic patients without clinical
      signs of arthritis (non-PsA psoriasis group), and healthy individuals, to detect
      subclinical PsA. METHODS: A total of 253 healthy volunteers, 242 non-PsA
      psoriatic patients, and 86 patients with PsA were assessed by 2-dimensional and
      power Doppler (PD) ultrasound. Peripheral joint, enthesis, tendon, and bursa
      abnormalities were observed, characterizing abnormal PD. The affected patients
      and sites with abnormalities in various ages were compared among groups; PD
      signal grades for the abnormalities were also compared. RESULTS: In the PsA
      group, significantly higher percentages of sites showing joint
      effusion/synovitis, enthesitis, and tenosynovitis in all age groups, and markedly
      higher rates of sites with bursitis were found in young and middle age groups,
      compared with the non-PsA and control groups (all p < 0.01). Meanwhile, the non
      PsA group showed significantly higher rates of joint effusion/synovitis and
      enthesitis sites, and elevated PD signal grades of synovitis, enthesitis, and
      tenosynovitis in comparison with the control group, both in young and middle age
      groups (all p < 0.01). CONCLUSION: Patients with PsA have high percentages and PD
      signal grades of peripheral joint, tendon, enthesis, and bursa involvement. Young
      and middle-aged non-PsA patients have high synovitis and enthesitis percentages,
      and elevated PD signal grades of synovitis, enthesitis, and tenosynovitis.

PMID- 29657141
TI  - Association of Serum Soluble CD163 with Polymyositis and Dermatomyositis,
      Especially in Anti-MDA5 Antibody-positive Cases.
AB  - OBJECTIVE: We elucidated the association of serum soluble CD163 (sCD163) with
      rapidly progressive interstitial lung disease (RP-ILD), autoantibody profiles,
      and serum ferritin in patients with polymyositis (PM), classic dermatomyositis
      (DM), and clinical amyopathic dermatomyositis (CADM). METHODS: Serum sCD163
      levels were retrospectively measured by ELISA in patients with PM, classic DM,
      and CADM, as well as in healthy controls (HC). Repeat sera samples were obtained
      posttreatment from available patients. The associations between serum sCD163
      levels and clinical information were analyzed. RESULTS: Serum sCD163 levels in
      patients with PM/classic DM/CADM were significantly higher than those in HC (n =
      72, 56, 34, and 68, respectively; p < 0.001 for all comparisons). No significant
      difference was observed between serum sCD163 levels in patients with and without
      ILD (p = 0.16) or between those with RP-ILD and chronic ILD (p = 0.21). Serum
      sCD163 levels were significantly higher in patients with anti-MDA5 antibodies (n
      = 27) than in those without (p = 0.001). Serum sCD163 levels were weakly
      correlated with serum ferritin levels in the patients with PM, classic DM, and
      CADM (r = 0.21). Serum sCD163 levels decreased significantly following treatment
      in all patient groups (p = 0.003). CONCLUSION: The present results suggest an
      association of serum sCD163 with PM, classic DM, and CADM, especially in anti
      MDA5 antibody-positive cases. However, serum sCD163 levels were not specifically
      associated with ILD or RP-ILD.

PMID- 29657140
TI  - Longterm Safety and Efficacy of Adalimumab and Infliximab for Uveitis Associated
      with Juvenile Idiopathic Arthritis.
AB  - OBJECTIVE: Anti-TNF-alpha agents have significantly changed the management of
      juvenile idiopathic arthritis (JIA). We evaluated the safety and efficacy of
      adalimumab (ADA) and infliximab (IFX) for the treatment of JIA-associated uveitis
      in patients treated for >= 2 years. METHODS: Patients with JIA-associated uveitis
      treated with IFX and ADA were managed by a standardized protocol and data were
      entered in the ORCHIDEA registry. At baseline, all patients were refractory to
      standard immunosuppressive treatment or were corticosteroid-dependent. Data
      recorded every 3 months were uveitis course, number/type of ocular flares and
      complications, drug-related adverse events (AE), and treatment switch or
      withdrawal. Data of patients treated for >= 2 years were analyzed by descriptive
      statistics. RESULTS: Up to December 2014, 154 patients with >= 24 months followup
      were included in the study. Fifty-nine patients were treated with IFX and 95 with
      ADA. Clinical remission, defined as the absence of flares for > 6 months on
      treatment, was achieved in 69 patients (44.8%), with a better remission rate for
      ADA (60.0%) as compared to IFX (20.3%; p < 0.001). A significant reduction of
      flares was observed in all patients without difference between the 2 treatment
      modalities. The number of new ocular complications decreased in both groups but
      was lower for ADA (p = 0.015). No serious AE were recorded; 16.4% of patients
      experienced 35 minor AE and the incidence rate was lower with ADA than with IFX.
      CONCLUSION: At the 2-year followup, ADA showed a better efficacy and safety
      profile than IFX for the treatment of refractory JIA-associated uveitis.

PMID- 29657142
TI  - Age- and Sex-dependent Frequency of Fat Metaplasia and Other Structural Changes
      of the Sacroiliac Joints in Patients without Axial Spondyloarthritis: A
      Retrospective, Cross-sectional MRI Study.
AB  - OBJECTIVE: To determine the prevalence of fat metaplasia and other structural
      lesions of the sacroiliac joints associated with axial spondyloarthritis in a
      nonrheumatological patient population. METHODS: Magnetic resonance imaging
      examinations that included the pelvis and were performed in patients without
      known rheumatological disease were used for this retrospective cross-sectional
      study. These images were evaluated for sacroiliac fat metaplasia, sclerosis,
      osteophytes, and joint space alterations such as erosions or ankylosis. Patients
      were divided into 7 age groups (15-24 to >= 75 yrs). Prevalence of lesions across
      age groups was calculated. Possible clinical confounders (e.g., status post
      radiation, suspected inflammatory bowel disease) were investigated regarding
      their effect on lesion prevalence and extent, to exclude bias. RESULTS: A total
      of 485 patients were enrolled. Fat metaplasia was very common and increased with
      age, from a prevalence of 50.6% in the age groups < 45, to 94.4% in patients >=
      75 years. Erosions were uncommon: 0.6% of patients < 45, and 2.6% of the entire
      study population exhibited this feature, with no detectable age-dependent
      increase. Sclerosis and osteophytes were detected in 13.7% and 37.0% of patients,
      respectively. None of the investigated clinical confounders had a significant
      effect on lesion prevalence. CONCLUSION: Our study shows a very high prevalence
      of fat metaplasia adjacent to the sacroiliac joint in asymptomatic patients,
      while erosions are extremely uncommon.

PMID- 29657143
TI  - Clinical and Serological Associations with the Development of Incident
      Proteinuria in Danish Patients with Systemic Lupus Erythematosus.
AB  - OBJECTIVE: In a longitudinal cohort study, we investigated whether clinical and
      serological manifestations at the time of classification of systemic lupus
      erythematosus (SLE) were predictive of subsequent development of incident
      proteinuria as a biomarker of incident lupus nephritis. METHODS: Patients
      fulfilling SLE classification criteria but having no proteinuria prior to or at
      the time of classification were included. Data on SLE manifestations, vital
      status, criteria-related autoantibodies, and SLE-associated medications were
      collected during clinical visits and supplemented by chart review. HR were
      calculated by Cox regression analyses. RESULTS: Out of 850 patients with SLE, 604
      had not developed proteinuria at the time of SLE classification. Of these 604
      patients, 184 (30%) developed incident proteinuria following SLE classification.
      The patients had a median followup of 11 years and 7 months. Younger age and
      history of psychosis at the time of classification were associated with
      development of incident proteinuria, just as were lymphopenia (HR 1.49, 95% CI
      1.08-2.06), anti-dsDNA (HR 1.38, 95% CI 1.01-1.87), and a high number of
      autoantibodies (HR 1.26, 95% CI 1.06-1.48). CONCLUSION: The risk of incident
      proteinuria after onset of SLE was increased by the presence of lymphopenia, anti
      dsDNA antibodies, psychosis, younger age, and a high number of autoantibodies at
      onset.

PMID- 29657144
TI  - Macrophage Activation Syndrome in Patients Affected by Adult-onset Still Disease:
      Analysis of Survival Rates and Predictive Factors in the Gruppo Italiano di
      Ricerca in Reumatologia Clinica e Sperimentale Cohort.
AB  - OBJECTIVE: Macrophage activation syndrome (MAS) is a reactive form of
      hemophagocytic lymphohistiocytosis, which can complicate adult-onset Still
      disease (AOSD). We investigated AOSD clinical features at the time of diagnosis,
      to assess predictors of MAS occurrence. Further, we analyzed the outcomes of
      patients with AOSD who experience MAS. METHODS: Patients with AOSD admitted to
      any Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale center were
      retrospectively analyzed for features typical of AOSD, MAS occurrence, and their
      survival rate. RESULTS: Of 119 patients with AOSD, 17 experienced MAS (12 at
      admission and 5 during followup). Twelve patients with MAS at first admission
      differed from the remaining 107 in prevalence of lymphadenopathy and liver
      involvement at the time of diagnosis. In addition, serum ferritin levels and
      systemic score values were significantly higher in the patients presenting with
      MAS. At the time of diagnosis, the 5 patients who developed MAS differed from the
      remaining 102 in the prevalence of abdominal pain, and they showed increased
      systemic score values. In the multivariate analysis, lymphadenopathy (OR 7.22,
      95% CI 1.49-34.97, p = 0.014) and abdominal pain (OR 4.36, 95% CI 1.24-15.39, p =
      0.022) were predictive of MAS occurrence. Finally, MAS occurrence significantly
      reduced the survival rate of patients with AOSD (p < 0.0001). CONCLUSION: MAS
      occurrence significantly reduced the survival rate in patients with AOSD.
      Patients with MAS at baseline presented an increased prevalence of
      lymphadenopathy and liver involvement, as well as high serum ferritin levels and
      systemic score values. The presence of lymphadenopathy and abdominal pain was
      associated with MAS occurrence.

PMID- 29657145
TI  - HLA-DRB1 Shared Epitope Alleles and Disease Activity Are Correlated with Reduced
      T Cell Receptor Repertoire Diversity in CD4+ T Cells in Rheumatoid Arthritis.
AB  - OBJECTIVE: Shared epitope (SE) alleles are the most significant genetic
      susceptibility locus in rheumatoid arthritis (RA); however, their target
      populations in CD4+ T cells are not well elucidated. We analyzed the association
      between SE alleles and the T cell receptor (TCR) repertoire diversity of naive
      and memory CD4+ T cells using next-generation sequencing (NGS). METHODS: The TCR
      beta chains in naive and memory CD4+ T cells from the peripheral blood of 22
      patients with RA and 18 age- and sex-matched healthy donors (HD) were analyzed by
      NGS. The Renyi entropy was used to evaluate TCR repertoire diversity and its
      correlations with SE alleles and other variables were examined. Serum cytokine
      levels were measured by multiplex ELISA. RESULTS: The TCR repertoire diversity in
      memory CD4+ T cells was reduced in SE allele-positive patients with RA compared
      with HD, and showed a significant negative correlation with the SE allele dosage
      in RA. The TCR repertoire diversity of naive and memory T cells was also
      negatively correlated with disease activity, and the SE allele dosage and disease
      activity were independently associated with reduced TCR repertoire diversity. TCR
      repertoire diversity showed a significant positive correlation with the serum
      interleukin 2 levels. CONCLUSION: SE alleles and disease activity were negatively
      correlated with the TCR repertoire diversity of CD4+ T cells in RA. Considering
      the pivotal role of CD4+ T cells in RA, restoring the altered TCR repertoire
      diversity will provide a potential RA therapeutic target.

PMID- 29657146
TI  - Absence of Fibrosis and Inflammation by Cardiac Magnetic Resonance Imaging in
      Rheumatoid Arthritis Patients with Low to Moderate Disease Activity.
AB  - OBJECTIVE: The prevalence of heart failure is increased 2-fold in patients with
      rheumatoid arthritis (RA); this is not explained by ischemic heart disease or
      other risk factors for heart failure. We hypothesized that in patients with RA
      without known heart disease, cardiac magnetic resonance imaging (cMRI) would
      detect altered cardiac structure, function, and fibrosis. METHODS: We performed
      1.5-T cMRI in 59 patients with RA and 56 controls frequency-matched for age,
      race, and sex, and compared cMRI indices of structure, function, and fibrosis
      [late gadolinium enhancement (LGE), native T1 mapping, and extracellular volume
      (ECV)] using Mann-Whitney U tests and linear regression, adjusting for age, race,
      and sex. RESULTS: Most patients with RA had low to moderate disease activity [28
      joint count Disease Activity Score-C-reactive protein median 3.16, interquartile
      range (IQR) 2.03-4.05], and 49% were receiving anti-tumor necrosis factor agents.
      Left ventricular (LV) mass, LV end-diastolic and -systolic volumes indexed to
      body surface area, and LV ejection fraction and left atrial size were not altered
      in RA compared to controls (all p > 0.05). Measures of fibrosis were not
      increased in RA: LGE was present in 2 patients with RA and 1 control subject;
      native T1 mapping was similar comparing RA and control subjects, and ECV (median,
      IQR) was lower (26.6%, 24.7-28.5%) in patients with RA compared to control
      subjects (27.5%, 25.4-30.4%, p = 0.03). CONCLUSION: cMRI measures of cardiac
      structure and function were not significantly altered, and measures of fibrosis
      were similar or lower in RA patients with low to moderate disease activity
      compared to a matched control group.

PMID- 29657147
TI  - Longterm Safety and Efficacy of Subcutaneous Abatacept in Patients with
      Rheumatoid Arthritis: 5-year Results from a Phase IIIb Trial.
AB  - OBJECTIVE: To assess 5-year safety, tolerability, and efficacy of subcutaneous
      (SC) abatacept (ABA) in methotrexate (MTX)-refractory patients with rheumatoid
      arthritis (RA). METHODS: The Abatacept Comparison of sub[QU]cutaneous versus
      intravenous in Inadequate Responders to methotrexatE (ACQUIRE) phase IIIb,
      randomized, double-dummy, multinational trial compared efficacy and safety of SC
      and intravenous (IV) ABA in patients with RA. In the initial 6-month double-blind
      (DB) period, patients received IV or SC ABA, plus MTX, and in the subsequent open
      label longterm extension (LTE) period, all patients received SC ABA (125 mg/wk).
      The final 5-year safety, tolerability, and efficacy analyses are reported.
      RESULTS: Of 1385 patients who completed the DB period, 1372 entered LTE and 945
      (68.8%) completed >= 5 years of treatment. During LTE, 97 (7.1%) patients
      discontinued treatment because of an adverse event (AE). Incidence rate (IR;
      event/100 patient-yrs of exposure; based on LTE data, 95% CI) for AE of interest
      were the following: serious AE 7.73 (6.96-8.58), infection 38.60 (36.24-41.12),
      serious infection 1.68 (1.35-2.07), malignancies 1.09 (0.84-1.42), and autoimmune
      disorders 1.33 (1.05-1.69), and were stable over time. No association between
      immunogenicity and either worsening of ABA safety or loss of efficacy was noted.
      Efficacy in the LTE was consistent with the DB period and was maintained to the
      end of the study. CONCLUSION: These 5-year data establish that SC ABA (125 mg/wk)
      has a consistent safety profile and durable efficacy for longterm treatment of
      patients with RA who had an inadequate response to MTX.

PMID- 29657148
TI  - The Prevalence of Renal Impairment in Patients with Spondyloarthritis: Results
      from the International ASAS-COMOSPA Study.
AB  - OBJECTIVE: To assess the prevalence and association of renal dysfunction in
      patients with spondyloarthritis (SpA). METHODS: The ASAS-COMOSPA (Assessment of
      Spondyloarthritis international Society-COMOrbidities in SPondyloArthritis) was
      an international study (22 participating countries from 4 continents)
      investigating comorbidities in SpA. Renal function was assessed based on
      estimated glomerular filtration rate (eGFR) calculated using the Modification of
      Diet in Renal Disease equation. SpA characteristics and risk factors for renal
      impairment were collected. Nonsteroidal antiinflammatory drug (NSAID) use was
      assessed based on current intake (last 3 mos). RESULTS: Of the 3984 patients
      recruited, 2098 (52.6%) were analyzed after excluding outliers and patients with
      no available eGFR measurement [male sex: 63.5%; age: 45.3 yrs; disease duration:
      8.6 years; HLA-B27+: 73.1%; Bath Ankylosing Spondylitis Activity Index (BASDAI):
      3.6/10]. Overall, 153 patients (5.2%, mean age: 53.6 yrs) exhibited an eGFR < 60
      ml/min/1.73 m2. In univariate analysis, renal impairment was associated with age
      (p < 0.001), HLA-B27 positivity (p = 0.003), several cardiovascular (CV) risk
      factors (history of hypertension, p < 0.001; systolic blood pressure, p = 0.009;
      diabetes, p = 0.005; and Framingham risk score, p < 0.001), disease activity
      scores [BASDAI, p = 0.001; Ankylosing Spondylitis Disease Activity Score-C
      reactive protein (ASDAS-CRP), p < 0.001], functional variables (Bath Ankylosing
      Spondylitis Functional Index, p < 0.001), inflammatory biomarkers (erythrocyte
      and CRP, both p < 0.001), and NSAID intake since onset of disease (percentage of
      days, p = 0.008). However, there was no association with disease duration,
      disease severity, or ASAS-NSAID score. In multivariate analysis, age (45-59 yrs:
      OR 1.9, > 60 yrs: OR 6.2), HLA-B27 positivity (OR 0.51), and CRP (OR 1.3)
      remained significantly associated with eGFR < 60 ml/min/1.73 m2. CONCLUSION:
      Renal impairment was associated with age, HLA-B27 positivity, and inflammation,
      though not with CV risk factors, disease severity, or NSAID intake in patients
      with SpA.

PMID- 29657149
TI  - The Natural Course of Diffuse Idiopathic Skeletal Hyperostosis in the Thoracic
      Spine of Adult Males.
AB  - OBJECTIVE: Diffuse idiopathic skeletal hyperostosis (DISH) is characterized by
      flowing bony bridges on the right side of the spine. Knowledge of the development
      of these spinal bridges is limited. The current longitudinal computed tomography
      (CT) study was designed to bridge this gap. METHODS: Chest CT scans from elderly
      males with 2 scans (interval >= 2.5 yrs) were retrospectively included. Using the
      Resnick criteria, a pre-DISH group and a definite DISH group were identified. A
      scoring system based on the completeness of a bone bridge (score 0-3), extent of
      fluency, and location of the new bone was created to evaluate the progression of
      bone formation. RESULTS: In total, 145 of 1367 subjects were allocated to the
      DISH groups with a mean followup period of 5 years. Overall prevalence of a
      complete bone bridge increased in the pre-DISH group (11.3% to 31.0%) and in the
      definite DISH group (45.0% to 55.8%). The mean bridge score increased
      significantly in both the pre-DISH and definite DISH group (p < 0.001). The new
      bone gradually became more flowing and expanded circumferentially. CONCLUSION:
      Over the mean course of 5 years, the new bone developed from incomplete, pointy
      bone bridges to more flowing complete bridges. This suggests an ongoing and
      measurable bone-forming process that continues to progress, also in established
      cases of DISH.

PMID- 29657150
TI  - Causes and Predictors of Early Hospital Readmission in Systemic Lupus
      Erythematosus.
AB  - OBJECTIVE: We investigated characteristics of adult patients with systemic lupus
      erythematosus (SLE) readmitted to the hospital within 30 days of discharge, in an
      attempt to identify the causes of early readmission. METHODS: We performed a
      retrospective case-control study examining all inpatient electronic health
      records of patients with SLE at Cedars-Sinai Medical Center over a 2.5-year
      period (2012-2014). Patients were included if they had an International
      Classification of Diseases, 9th ed diagnosis of SLE and were readmitted within 30
      days of their initial hospitalization. Patients with SLE not readmitted during
      this time period were used as a control group. Demographic and clinical variables
      for each patient were collected, and we used the Charlson Comorbidity Index to
      characterize comorbidities. The Systemic Lupus International Collaborating
      Clinics/American College of Rheumatology Damage Index (SDI) was used to assess
      the chronic damage of SLE. Stepwise multivariable logistic regression analysis
      was used to predict factors associated with readmission. RESULTS: In total, 570
      hospitalizations representing 455 unique patients met our inclusion and exclusion
      criteria. Of these, 154 patients (34%) underwent readmission within 30 days of
      their initial hospitalization. Patients in the early readmission group were more
      likely to have government-sponsored Medicaid insurance and were significantly
      associated with an increased SDI (OR 1.27, 95% CI 1.1-1.48), lower serum
      hemoglobin (OR 0.82, 95% CI 0.72-0.93), and lower serum albumin (OR 0.66, 95% CI
      0.47-0.91). CONCLUSION: One-third of hospitalized patients with SLE were
      readmitted within 30 days at our institution. We identified characteristics of
      this at-risk population at time of discharge with high specificity, in hopes of
      reducing this costly outcome.

PMID- 29657152
TI  - Venous Thromboembolism in Systemic Sclerosis: Prevalence, Risk Factors, and
      Effect on Survival.
AB  - OBJECTIVE: Whether systemic sclerosis (SSc) confers increased risk of venous
      thromboembolism (VTE) is uncertain. We evaluated the prevalence, risk factors,
      and effect of VTE on SSc survival. METHODS: A cohort study was conducted of
      subjects with SSc who fulfilled the American College of Rheumatology/European
      League Against Rheumatism classification criteria between 1970 and 2017. Deep
      vein thrombosis was defined as thrombus on extremity ultrasound. Pulmonary
      embolism was defined as thrombus on thorax computed tomography angiogram. Risk
      factors for VTE and time to all-cause mortality were evaluated. RESULTS: Of the
      1181 subjects, 40 (3.4%) experienced VTE events. The cumulative incidence of VTE
      was 2.7 (95% CI 1.9-3.7) per 1000 patient-years. Pulmonary arterial hypertension
      (PAH; OR 3.77, 95% CI 1.83-8.17), peripheral arterial disease (OR 5.31, 95% CI
      1.99-12.92), Scl-70 (OR 2.45, 95% CI 1.07-5.30), and anticardiolipin antibodies
      (OR 5.70, 95% CI 1.16-21.17) were predictors of VTE. There were 440 deaths. There
      was no difference in survival between those with and without VTE (HR 1.16, 95% CI
      0.70-1.91). Interstitial lung disease (HR 1.54, 95% CI 1.27-1.88) and PAH (HR
      1.35, 95% CI 1.10-1.65) were predictors of mortality. CONCLUSION: The risk of VTE
      in SSc is comparable to the general population. The presence of PAH, peripheral
      arterial disease, Scl-70, and anticardiolipin antibodies are risk factors for
      VTE. VTE does not independently predict SSc survival.

PMID- 29657151
TI  - Crystal-proven Gout and Characteristic Gout Severity Factors Are Associated with
      Cardiovascular Disease.
AB  - OBJECTIVE: Our aim was to examine the prevalence of cardiovascular disease (CVD)
      in patients with crystal-proven gout compared to arthritis controls. Further, we
      analyzed the association between characteristic gout severity factors and CVD to
      provide further support for a pathogenetic relationship between gout and CVD.
      METHODS: Patients with arthritis referred for diagnosis were consecutively
      included in the Gout Arnhem-Liemers cohort. Joint fluid analysis was performed in
      all referred patients; controls were negative for crystals. Patients'
      characteristics and different manifestations of CVD and gout severity factors
      (disease duration, attack frequency, tophi, affected joints, high serum urate
      acid level, joint damage) were collected. Gout patients were compared with
      controls for the prevalence of CVD. In addition, the association between
      characteristic gout severity factors and presence of CVD was analyzed. RESULTS:
      Data from 700 gout patients and 276 controls were collected. CVD was present in
      47% (95% CI 44%-51%) and 24% (95% CI 19%-29%) of gout patients and controls,
      respectively. Corrected for confounders, gout was still strongly associated with
      an increased prevalence of CVD compared to controls (OR 3.39, 95% CI 2.37-4.84).
      In patients with gout, disease duration >= 2 years, oligo- or polyarthritis,
      serum urate acid > 0.55 mmol/l at presentation, and joint damage were
      independently (p < 0.05) associated with prevalent CVD. CONCLUSION: Crystal
      proven gout was strongly associated with an increased prevalence of CVD. In
      patients with gout, characteristic gout severity factors were associated with
      CVD.

PMID- 29657153
TI  - Repeat Testing of Antibodies and Complements in Systemic Lupus Erythematosus:
      When Is It Enough?
AB  - OBJECTIVE: Patients with systemic lupus erythematosus (SLE) frequently undergo
      repeat testing for antibodies against extractable nuclear antigens (anti-ENA),
      but it is not known whether this is necessary or cost-effective. This study
      characterized the frequencies of changes in anti-ENA, anti-dsDNA, and complement
      C3 and C4 upon repeat testing. METHODS: Chart review was done at one site of 130
      patients with SLE enrolled in the 1000 Canadian Faces of Lupus prospective
      registry with annual antibody and complement testing. We determined the frequency
      of seroconversion (changes) on the next test and over the entire followup given 1
      or multiple consistent results, and the cost to detect these changes. RESULTS:
      Overall, 89.4% of patients had no changes in anti-ENA screening results from the
      first available test, 3.3% changed from negative to positive, and 7.3% from
      positive to negative. Following a single anti-ENA test, 3.9% of negative tests
      changed to positive and 4.2% of positive changed to negative on the next test.
      After multiple consistent tests, the frequencies of changes progressively
      declined. No changes from the first test were observed in anti-dsDNA, C3, and C4
      in 60.8%, 83.3%, and 75.4% of patients, respectively. After 2 consistent anti-ENA
      tests, the cost to detect 1 change was above US$2000. CONCLUSION: Anti-ENA
      results change infrequently, especially following 1 or more negative tests. The
      high cost and lack of evidence that changes affect management suggest that
      repeating anti-ENA tests routinely is unnecessary. Anti-dsDNA and complements
      change more frequently after an abnormal result, but less after a normal value.

PMID- 29657155
TI  - Harmonisation of standards for permissible radionuclide activity concentrations
      in foodstuffs in the long term after the Chernobyl accident.
AB  - The article critically examines the practice of post-Chernobyl standardisation of
      radionuclide concentrations (mainly 137Cs and 90Sr) in food products (FPs) in the
      USSR and the successor countries of Belarus, Russia and Ukraine. Recommendations
      are given on potential harmonisation of these standards of radionuclide
      concentrations in FPs among the three countries, taking into account substantial
      international experience. We propose to reduce the number of product groups for
      standardisation purposes from the current amount of several dozens to three to
      five groups to optimise radiation control and increase the transparency of the
      process. We recommend five product groups for the standardisation of 137Cs and
      three groups for 90Sr in food in radiocontaminated areas. The values of standards
      for individual product groups are recommended to be set proportionally to the
      measured specific activity in each of these groups, which will reduce
      unreasonable food rejection. The standards might be set for the entire country,
      and could be also used to control imports from other countries as well as exports
      to other countries. The developed recommendations were transferred in 2015-2016
      to the regulatory authorities of the three countries.

PMID- 29657154
TI  - Two new species of Hepatozoon (Apicomplexa: Hepatozoidae) parasitising species of
      Philothamnus (Ophidia: Colubridae) from South Africa.
AB  - To date, only a few species of Hepatozoon Miller, 1908 have been described from
      amphibians and reptiles of South Africa, including two species from anuran hosts,
      three from saurians, one from chelonians, and two from ophidians. Hepatozoon
      bitis (Fantham, 1925) and Hepatozoon refringens (Sambon et Seligmann, 1907),
      parasitising Bitis arientans (Merrem) and Pseudoaspis cana (Linnaeus),
      respectively, were described in the early 1900s and since then there have been no
      further species of Hepatozoon described from snakes in South Africa. Blood
      smears, used in peripheral blood haemogregarine stage morphometrics, and whole
      blood used in molecular characterisation of haemogregarines were collected from
      the caudal vein of six snakes of three species, namely Philothamnus hoplogaster
      (Gunther), Philothamnus semivariegatus (Smith) and Philothamnus natalensis
      natalensis (Smith). For comparison, a comprehensive table summarising available
      information on species of Hepatozoon from African snakes is presented.
      Haemogregarines found infecting the snakes from the present study were
      morphologically and molecularly different from any previously described from
      Africa and are thus here described as Hepatozoon angeladaviesae sp. n. and
      Hepatozoon cecilhoarei sp. n. Both haemogregarine species were observed to cause
      considerable dehaemoglobinisation of the host cell, in case of infection with H.
      angeladaviesae resulting in a characteristic peripheral undulation of the host
      cell membrane and karyorrhexis. To the authors' knowledge, these are the first
      haemogregarines parasitising snakes of the genus Philothamnus Smith described
      using both morphological and molecular characteristics in Africa.

PMID- 29657156
TI  - Effects of titanium surface roughness on the mediation of osteogenesis via
      modulating the immune response of macrophages.
AB  - Osteoblastic lineage cells are commonly used to evaluate the in vitro osteogenic
      ability of bone biomaterials. However, contradictory results obtained from in
      vivo and in vitro studies are not uncommon. With the increasing understanding of
      osteoimmunology, the immune response has been recognized as playing an important
      role in bone regeneration. In this study, we examined the effect of submicron
      scaled titanium surface roughness (ranging from approximately 100 to 400 nm) on
      the response of osteoblasts and macrophages. The results showed that osteoblast
      differentiation enhanced with increased surface roughness of titanium substrates.
      The cytoskeleton of macrophages altered with the variation in titanium surface
      roughness. The production of cytokines (TNF-alpha, IL-6, IL-4 and IL-10) could be
      regulated by titanium surface roughness. Moreover, macrophages cultured on
      titanium surfaces exhibited a tendency to polarize to M1 phenotype with the
      increase of surface roughness. Material/macrophage conditioned medium tended to
      promote osteoblast differentiation with the increase of surface roughness. The
      results indicate that increasing surface roughness in the submicron range is
      beneficial for osteogenesis via modulating the immune response of macrophages.
      Modifying biomaterial surfaces based on their immunomodulatory effects is
      considered as a novel strategy for the improvement of their biological
      performance.

PMID- 29657157
TI  - The Doctor in the Family.

PMID- 29657158
TI  - Doctor in the Family or Family Doctor?

PMID- 29657159
TI  - Moving Through and Moving Forward.

PMID- 29657161
TI  - Everyone should have a physician in the family.

PMID- 29657160
TI  - DNR for a Survivor.

PMID- 29657162
TI  - Editors' Note.

PMID- 29657163
TI  - Watershed and Intersections: The Doctor in the Family.

PMID- 29657164
TI  - Doctor in the Family: Stories and Dilemmas Surrounding Illness in Relatives.
AB  - This symposium includes twelve personal narratives from physicians with family
      members or close personal friends with medical illnesses. This issue also
      includes three commentaries on these narratives by scholars in the fields of
      bioethics, sociology, and law. The aim of this issue is to explore the benefits
      and potential harms that may arise when physicians are involved in the care of
      relatives, a role often fraught with conflicting moral obligations.

PMID- 29657165
TI  - Family Portrait.

PMID- 29657166
TI  - Found in the Translation.

PMID- 29657167
TI  - Let Me Hold the Wheel, Daddy!

PMID- 29657168
TI  - Caution Ahead-Physician Parent.

PMID- 29657169
TI  - A Family Affair.

PMID- 29657170
TI  - PICU Doctor in the Family.

PMID- 29657171
TI  - For the Love of Tomatoes and Movies: Lessons from a Grandfather's Passing.

PMID- 29657172
TI  - A Family Physician: My Role and My Specialty.

PMID- 29657174
TI  - Recognising Illness in a Loved One: The Obligation to Speak, the Pull of Silence.

PMID- 29657173
TI  - My Father, My Patient.

PMID- 29657175
TI  - Abdicating the Role of Physician, Losing the Role of Loved One.

PMID- 29657176
TI  - Between a Father and a Son.

PMID- 29657177
TI  - When Professional Rightness is Personal.
AB  - This commentary discusses twelve stories in which physicians tell what happened
      when they were involved in the care of a family member. The stories display
      considerable differences in attitude toward the ethics and usefulness of
      physicians treating members of their own families. But the more significant
      tension is between the analytical or objective attitude that all the writers
      presuppose as necessary for doing good medical work, opposed to the emotions
      aroused by seeing a loved one suffer. The commentary explores the implications of
      assuming this binary opposition, whether it is correct, and how far it is
      actually necessary. Concluding comments discuss what kind of ethics is involved
      in stories that are all about dilemmas and decisions, but rarely invoke concepts
      from bioethics.

PMID- 29657178
TI  - Doctor in, and for, the Family?: Physicians Reflect on Care for Loved Ones.
AB  - This commentary examines themes identified in twelve physicians' narratives
      recounting their experiences in caring for seriously ill family members. In these
      narratives, physicians describe heavy emotional burdens and other impediments to
      sound medical decision-making with and for their loved ones. The physicians
      struggled to balance their roles as physicians and as loving family members, and
      they employed their professional role in a variety of different ways. Several
      physicians became personal physicians to their family members, and others
      deliberately avoided that role. Serving as personal physician to a close family
      member is widely viewed as a violation of a professional boundary, and adopting
      that role may expose physicians to sanctions. These narratives offer lessons to
      physicians regarding their roles in caring for family members and in supporting
      family members of patients with grave illnesses.

PMID- 29657179
TI  - The Dilemma of the "Doctor in the Family".
AB  - The twelve narratives written by physicians for this symposium address the same
      question: "What happens when I wear a white physician's coat at the bedside of an
      ill or dying family member or friend?" This commentary addresses several key
      themes, which emerged as the author reacted to these narratives: (1) the
      physicians did not mention policy issues affecting the public inherent in a
      health system regulated by statutes and paid for by insurers; (2) the physicians
      did not follow the ethical rule against treating family members; (3) there was no
      discussion of whether hospital ethics committees or similar advisory bodies might
      have helped address conflicts as they arose; and (4) there was minimal discussion
      of Advance Medical Directives and Do Not Resuscitate Orders. These narratives
      show why individual experiences should have a strong voice in the debates over
      health care and health policy.

PMID- 29657180
TI  - Views of Low-Income Women of Color at Increased Risk for Breast Cancer.
AB  - Individual risk assessment (IRA) for breast cancer may increase adherence to risk
      appropriate screening and prevention measures. However, knowledge gaps exist
      regarding how best to communicate IRA results and support women at increased risk
      in future health care decisions, in part because patients conceptualize and make
      meaning of risk differently from the medical community. Better understanding the
      views of low-income women of color identified as being at increased risk for
      breast cancer can inform efforts to conduct IRA in an ethical and respectful
      manner. We conducted in-depth interviews with 13 low-income African American and
      Latina women who receive care at a federally qualified health center (FQHC) and
      had recently learned of their increased risk for breast cancer. These interviews
      explored their experience of the IRA process, their interpretation of what being
      at increased risk means, and their reactions to provider recommendations. Eight
      key themes were identified. We conclude with recommendations for the
      implementation of IRA for breast cancer in underserved primary care settings.

PMID- 29657182
TI  - Editors' Note.

PMID- 29657181
TI  - A Personal Narrative on Living and Dealing with Psychiatric Symptoms after DBS
      Surgery.
AB  - Although deep brain stimulation (DBS) may result in dramatic motor improvement in
      people with Parkinson's disease (PD), it has been correlated with a number of
      postoperative psychiatric side effects. We report a case of a person with PD
      experiencing depression and hypomania following DBS surgery. We provide a
      detailed report of the patient's personal experiences dealing with and managing
      these psychiatric side effects for three years. Providing a personal narrative
      focusing on detailed patient subjective experiences complements reports that give
      insight into the short- and long-term effects of DBS on established psychiatric
      measures and neurologic activity. But, most importantly, such a qualitative
      approach provides prospective patients and clinicians with a broader ethical
      picture of real-life challenges faced and coping strategies employed by PD
      patients treated with DBS who are experiencing psychiatric adverse events. This
      case study reinforces the ethical need to disclose the potential risk of harm to
      prospective patients as well as the importance of establishing a
      multidisciplinary postoperative supportive group.

PMID- 29657183
TI  - Supplement: Veterans' Health Care on the Home Front.

PMID- 29657185
TI  - Blindsided Abroad.

PMID- 29657184
TI  - The Price of Dependence.

PMID- 29657186
TI  - What We Miss, or Ignore, or Refuse to See.

PMID- 29657187
TI  - Shitbag! An Autobigraphical Essay.

PMID- 29657189
TI  - Limited patient choice within the Military Health System.

PMID- 29657188
TI  - From Army service to physician to patient.

PMID- 29657190
TI  - Fighting for Freedom by Killing the Pain.
AB  - This symposium includes six personal narratives about military veterans'
      experiences receiving health care through the Military Health System or the
      Veterans' Health Administration. Five of the narratives were autobiographical
      accounts of men's personal experience of care and one of the accounts was written
      by a wife who watched her husband suffer with chronic pain after leaving the
      military. There is a good deal of literature in military and veteran's medical
      research pertaining to psychological and physical trauma rehabilitation; however,
      there is little reflection on what it is like for injured military personnel or
      veterans to overcome obstacles while in pain and attempting interface with these
      governmental health care systems. This symposium provides a closer look at the
      difficulties faced as these six men attempt to fight for personalized care in a
      collective heath care system.

PMID- 29657191
TI  - Erratum: Intracutaneous pharmacokinetics of oral antifungals and their relevance
      in recalcitrant cutaneous dermatophytosis: Time to revisit basics.
AB  - [This corrects the article DOI: 10.4103/ijdvl.IJDVL_1012_16].

PMID- 29657192
TI  - What we do and do not know about women and kidney diseases; Questions unanswered
      and answers unquestioned: Reflection on World Kidney Day and International
      Woman's Day.
AB  - Chronic Kidney Disease affects approximately 10% of the world's adult population:
      it is within the top 20 causes of death worldwide, and its impact on patients and
      their families can be devastating. World Kidney Day and International Women's Day
      in 2018 coincide, thus offering an opportunity to reflect on the importance of
      women's health and specifically their kidney health, on the community, and the
      next generations, as well as to strive to be more curious about the unique
      aspects of kidney disease in women so that we may apply those learnings more
      broadly. Girls and women, who make up approximately 50% of the world's
      population, are important contributors to society and their families. Gender
      differences continue to exist around the world in access to education, medical
      care, and participation in clinical studies. Pregnancy is a unique state for
      women, offering an opportunity for diagnosis of kidney disease, but also a state
      where acute and chronic kidney diseases may manifest, and which may impact future
      generations with respect to kidney health. There are various autoimmune and other
      conditions that are more likely to impact women with profound consequences for
      child bearing, and on the fetus. Women have different complications on dialysis
      than men, and are more likely to be donors than recipients of kidney transplants.
      In this editorial, we focus on what we do and do not know about women, kidney
      health, and kidney disease, and what we might learn in the future to improve
      outcomes worldwide. Kidney Health and Women's Health: a case for optimizing
      outcomes for present and future generations.

PMID- 29657193
TI  - Atypical hemolytic uremic syndrome: Laboratory characteristics, complement
      amplifying conditions, renal biopsy, and genetic mutations.
AB  - Atypical hemolytic uremic syndrome (aHUS) is characterized by microangiopathic
      hemolytic anemia, consumptive thrombocytopenia, and widespread damage to multiple
      organs including the kidney. The syndrome has a high mortality necessitating the
      need for an early diagnosis to limit target organ damage. Because thrombotic
      microangiopathies present with similar clinical picture, accurate diagnosis of
      aHUS continues to pose a diagnostic challenge. This article focuses on the role
      of four distinct aspects of aHUS that assist clinicians in making an accurate
      diagnosis of aHUS. First, because of the lack of a single specific laboratory
      test for aHUS, other forms of thrombotic microangiopathies such as thrombotic
      thrombocytopenic purpura and Shiga toxin-associated HUS must be excluded to
      successfully establish the diagnosis of aHUS. Second, application of the
      knowledge of complement-amplifying conditions is critically important in making
      an accurate diagnosis. Third, when available, a renal biopsy can reveal changes
      consistent with thrombotic microangiopathy. Fourth, genetic mutations are
      increasingly clarifying the underlying complement dysfunction and gaining
      importance in the diagnosis and management of patients with aHUS. This review
      concentrates on the four aspects of aHUS and calls for heightened awareness in
      making an accurate diagnosis of aHUS.

PMID- 29657194
TI  - Association of brucellosis with renal tubular and glomerular damage in children
      in Turkey.
AB  - Brucellosis is a multisystem disease that may present with a broad spectrum of
      clinical manifestations. Until now, no studies have been performed on renal
      tubular disorders in patients with brucellosis. The present study aims to
      investigate renal tubular disorders in patients with brucellosis. This
      prospective case-control study includes a total of 31 brucellosis patients (Group
      1) and 30 healthy controls (Group 2) matched for age and sex. Renal tubular
      functions of children who were diagnosed as having brucellosis in outpatient
      pediatric clinics were evaluated. First-morning urine samples were collected from
      Group 1 and Group 2 at the same time. Urea, creatinine, potassium, sodium, and
      phosphorus were determined in serum and urine by an autoanalyzer. Tubular
      reabsorption and excretion of urine electrolytes were calculated using the
      related formulas. Patients with brucellosis had significantly lower levels of
      tubular reabsorption of phosphorus and serum phosphorus than those of the control
      group. Furthermore, urine sodium and serum potassium levels and fractionated
      sodium excretion of brucellosis patients were significantly higher than healthy
      control group. Estimated glomerular filtration rate was remarkably higher in the
      patient group (P < 0.001).We concluded that tubular and glomerular functional
      parameters demonstrate deterioration in patients with brucellosis compared to
      those in healthy participants.

PMID- 29657195
TI  - Evaluation of serum soluble urokinase plasminogen activator receptor as a marker
      for steroid-responsiveness in children with primary nephrotic syndrome.
AB  - Nephrotic syndrome (NS) is the most common primary glomerular disease among
      children. It runs a relapsing course involving prolonged periods of treatment
      with corticosteroids and other immunosuppressive medications. Soluble urokinase
      plasminogen activator receptor (suPAR) has been regarded as an inflammatory as
      well as a permeability factor. The aim of our study was to evaluate serum suPAR
      levels in children with NS and its relation to steroid responsiveness. Our study
      was carried out on 75 children who were already diagnosed as having NS; they were
      classified into three groups (steroid sensitive, steroid dependent, and steroid
      resistant). Furthermore, 40 apparently healthy children, age and sex matched with
      the NS patients, were enrolled as controls. All children had undergone assessment
      of serum suPAR, renal function tests (urea and creatinine), serum albumin, C
      reactive protein, and 24-h protein in urine. The study found that suPAR level was
      significantly different between the studied groups (P <0.05), being highest in
      steroid-resistant NS (66.52 +/- 9.7 ng/mL), followed by steroid dependent (56.82
      +/- 11.09 ng/mL), and steroid-sensitive patients (26.22 +/- 3.86 ng/mL), and
      lowest in the control group (20.29 +/- 0.69 ng/mL). When receiver operating
      characteristics curves were plotted, suPAR had high sensitivities and
      specificities in predicting steroid responsiveness, [area under the curve (AUC) =
      0.99, 95% confidence interval (CI) = 0.911-1.000, P <0.001], steroid dependence
      (AUC = 1.00, 95% CI = 0.929-1.000, P <0.001), and predicting steroid resistance.
      Our study indicates that suPAR is significantly higher in children with primary
      NS and varies according to their response to steroid therapy. It may act as a
      marker for steroid responsiveness in these children.

PMID- 29657196
TI  - Atypical hemolytic uremic syndrome: A monocentric adult Tunisian study and review
      of literature.
AB  - Atypical hemolytic uremic syndrome (aHUS) is characterized by microvascular
      thrombosis resulting in thrombocytopenia, hemolytic anemia, and multiorgan
      dysfunction. It is associated with genetic or acquired disorders of regulatory
      components of the complement system. For our study, we collected data from 16
      patients diagnosed with aHUS between January 2010 and January 2014. The mean age
      was 33.6 years. The female-to-male ratio was 3. The median follow-up duration was
      27 +/- 3.5 months. The most common clinical presentation was hypertension. Renal
      involvement was noted in all cases. Ten patients had extrarenal manifestations.
      Semi-quantitative dysfunction of the alternative pathway of complement was found
      in all cases. A genetic study was not available for our patients. During the
      acute stage, all patients received plasma therapy, and among them, seven required
      dialysis and five were still on dialysis at the time of discharge. One patient
      underwent renal transplantation. None of our patients received eculizumab
      perfusion. The renal survival was inversely correlated to young age (<30 years)
      (P = 0.001), presence of anti-factor H antibodies (P = 0.003) and serum
      creatinine at diagnosis >5 mg/dL (P = 0.02). Mortality rate was significantly
      correlated to young age (<30 years old) (P = 0.01). Collecting multicentric data
      on adult patients with aHUS will enable better characterization of the spectrum
      of adult aHUS in our country and the evaluation of current treatments and
      different outcomes.

PMID- 29657197
TI  - ADAMTS-13 level in children with severe diarrhea-associated hemolytic uremic
      syndrome: Unmasking new association.
AB  - Severe deficiency of ADAMTS-13 leads to thrombotic thrombocytopenic purpura. Few
      studies have reported reduced activity of ADAMTS-13 in patients with atypical and
      typical hemolytic uremic syndrome (HUS). We hypothesized that ADAMTS-13
      deficiency might play a role in the pathogenesis of severe HUS. This study aimed
      to evaluate the ADAMTS-13 level in severe typical HUS. This prospective case
      control study was carried out in the Pediatric Nephrology Unit and Clinical
      Pathology Department, Faculty of Medicine, Zagazig University from February 2013
      to February 2014. The study included 15 consecutive children with typical HUS as
      well as 15 healthy children as a control group. Routine laboratory investigations
      were performed. Assessment of serum ADAMTS-13 level was performed using the
      Quantikine human ADAMTS-13 ELISA kit. Data were analyzed using Statistical
      Package for Social Sciences version 16. Nonparametric values were expressed as
      median and range, and the median of two groups was tested by Mann-Whitney test.
      The serum ADAMTS-13 level was significantly lower in HUS patients when compared
      to the control group (P < 0.05). There were significant negative correlations
      between ADAMTS-13 level and duration on dialysis, as well as serum urea and
      creatinine. Furthermore, there were significant positive correlations between
      serum ADAMTS-13 level and both hemoglobin level and platelet count. Our study
      suggests that the ADAMTS-13 level was decreased in children with severe typical
      HUS and its deficiency correlated with disease severity.

PMID- 29657198
TI  - Scoring systems and outcome of chronic kidney disease patients admitted in
      intensive care units.
AB  - The outcome of chronic kidney disease (CKD) patients admitted to the Intensive
      Care Unit (ICU) is difficult to predict. This study assessed the outcome of CKD
      patients admitted to the ICU and evaluated prediction of 30-day mortality using
      the Acute Physiology and Chronic Health Evaluation (APACHE II), Simplified Acute
      Physiology Score (SAPS II), and Sequential Organ Failure Assessment (SOFA) score.
      One hundred consecutive CKD patients admitted to the ICU at a tertiary care
      hospital, Ahmedabad between 2011 and 2013 were included prospectively. Data on
      demographics, indication for admission, cause of CKD, use of vasoactive drugs and
      mechanical ventilation (MV), mode of renal replacement therapy (RRT), and 30-day
      mortality were recorded. The APACHE II, SAPS II, and SOFA scores were calculated
      based on the admission characteristics. The mean APACHE II, SAPS II, and SOFA
      scores were 28.22 +/- 7.53, 43.04 +/- 16.40, and 10.39 +/- 5.20, respectively,
      and area under receiver operating characteristics curve in predicting 30-day
      mortality were 0.961, 0.994, and 0.950, respectively. The scores were
      significantly higher in 30-day nonsurvivors as compared to survivors (P = 0.001).
      During the ICU stay, MV and vasoactive drugs were required in 57% and 67% of the
      patients, respectively, and the requirement was significantly greater in
      nonsurvivors as compared to survivors (P = 0.001). About 85% of patients were on
      intermittent hemodialysis and 15% of patients were on continuous venovenous
      hemodiafiltration. Sepsis was the main reason for hospital admission, and the
      mean length of stay in the ICU was 7.74 +/- 5.34 days. The study indicates that
      all three scores (APACHE II, SAPS II, and SOFA) perform equally well and have
      equal diagnostic utility in predicting 30-day mortality.

PMID- 29657199
TI  - Impact of body mass index on progression of primary immunoglobulin a nephropathy.
AB  - The role of obesity in the progression of primary glomerular diseases is
      controversial. A few studies report overweight/obesity as a risk factor for
      disease progression in immunoglobulin A nephropathy (IgAN), and the real impact
      of it still remains unclear. The aim of this study was to elucidate the effect of
      body mass index (BMI) on disease progression and proteinuria in patients with
      IgAN in Indian population. A cohort of biopsy-proven primary IgAN patients
      diagnosed between March 2010 and February 2015 who had a follow-up for a minimum
      of 12 months were included in the study. We defined two groups of patients
      according to the BMI value at diagnosis: non-obese group (Group N) with BMI <23
      Kg/m2 and the overweight/obese group (Group O) with BMI >23 Kg/m2 as per Asia
      Pacific task force criteria. Baseline characteristics were compared between the
      groups. The estimated glomerular filtration rate (eGFR) and urine protein
      creatinine ratio (UPCR) were followed up at entry time, 6 months, 12 months, and
      at the end of follow-up. Outcomes studied were change in eGFR, proteinuria, and
      progression to end-stage renal disease. Statistical analysis was done using the
      Statistical Package for the Social Sciences version 15.0. Of 51 patients, 25
      (49%) had BMI <23 kg/m2 (Group N) and 26 (51%) had BMI >23 kg/m2 (Group O) (P =
      0.01). The baseline clinical, histopathological, and treatment characteristics of
      both the groups were comparable. The BMI at the time of diagnosis did not have
      any significant effect on eGFR (P = 0.41) or proteinuria (P = 0.99) at
      presentation. At the end of follow-up, both the groups had a similar reduction of
      proteinuria (UPCR) (P = 0.46) and eGFR (P = 0.20). Two patients in each group
      have reached chronic kidney disease Stage 5. In the present study, BMI at
      presentation did not have any impact on eGFR or proteinuria, either at diagnosis
      or at follow-up. It needs further large multicenter randomized control studies to
      see the effect of BMI on progression of IgAN.

PMID- 29657200
TI  - Complementary bodybuilding: A potential risk for permanent kidney disease.
AB  - We report our experience of renal disease associated with bodybuilders who had
      been on high-protein diet, anabolic androgenic steroids (AASs), and growth
      hormone (GH) for years. A total of 22 adult males who volunteered information
      about use of high protein diet and AAS or GH were seen over a six-year period
      with renal disease. Kidney biopsy revealed focal segmental glomerulosclerosis
      (FSGS) in eight, nephroangiosclerosis in four, chronic interstitial nephritis in
      three, acute interstitial nephritis in two, nephrocalcinosis with chronic
      interstitial nephritis in two, and single patients with membranous
      glomerulopathy, crescentic glomerulopathy, and sclerosing glomerulonephritis.
      Patients with FSGS had a longer duration of exposure, late presentation, and
      worse prognosis. Those with interstitial disease had shorter exposure time and
      earlier presentation and had improved or stabilized after discontinuation of
      their practice. There is a need for health education for athletes and
      bodybuilders to inform them about the risks of renal disease involved with the
      use of high-protein diet, AAS, and GH.

PMID- 29657201
TI  - Prevalence of malnutrition in hemodialysis patients: A single-center study in
      Palestine.
AB  - Only a few studies have been published on the nutritional status of hemodialysis
      (HD) patients in Arab countries. The aim of this study was to determine the
      nutritional status and prevalence of malnutrition and its predictors among HD
      patients at An-Najah National University Hospital, Nablus, Palestine. A cross
      sectional study was carried out on HD patients in this hospital. Seven-Point
      Subjective Global Assessment (7-point SGA) was used to assess the nutritional
      state of HD patients. Biochemical tests were obtained during the study period
      from medical files of the studied patients. A total of 106 HD patients were
      recruited for this study and assessed for nutritional status. More than half (60,
      56.6%) of the recruited patients were males. The majority of the patients (86.8%)
      were above 45 years of age. Hypertension (65, 61.3%) was the most common comorbid
      conditions followed by diabetes mellitus (51, 48.1%). The median SGA score was
      5.57 (5-6). More than half of the HD patients (56; 52.8%) were well-nourished
      while the remaining (50, 47.2%) had mild-to-moderate malnourishment. Univariate
      analysis indicated that SGA score was significantly higher in HD patients with
      college education (P = 0.026), nondiabetic (P = 0.044), nonhypertensive (P =
      0.037), and those with current occupation (P = 0.025). No significant correlation
      was found between SGA score and potassium level (P = 0.134), calcium level (P =
      0.883), albumin (P = 0.282), and phosphate level (P = 0.419). However,
      significant positive correlation was found between SGA core and hemoglobin level
      (P = 0.019; r = 0.227). Multivariate analysis showed no significant predictors of
      SGA score. In this pilot single-center study, malnutrition was detected in almost
      half of HD patients using SGA scale. Development of nutritional assessment
      protocols for HD is an important issue and needs to be followed up by health-care
      teams in HD centers.

PMID- 29657202
TI  - Outcomes of immunosuppression in IgA nephropathy based on the oxford
      classification.
AB  - Numerous studies have addressed the predictive value of pathology findings from
      the Oxford Classification. Whether this influences treatment choice has not been
      determined. We evaluated patients with IgA nephropathy who were immunosuppressed
      and correlated our findings with both clinical and histological features as per
      the Oxford Classification. This was a retrospective observational study of 45
      patients who had biopsy-proven IgA nephropathy with a mean follow-up of 2.6
      years. Primary outcomes were time to end-stage renal disease (ESRD) or a 50% rise
      in serum creatinine. Immunosuppression was not associated with lower hazards for
      both ESRD and 50% rise in serum creatinine. From the Oxford Classification, only
      T0 was associated with significantly lower hazards for ESRD [hazard ratio (HR),
      0.067; confidence interval (CI) 0.01-0.58]. Patients who had crescents and/or
      necrotizing lesions on biopsy were more likely to be immunosuppressed (odds ratio
      9.99; 95% CI 1.99-50.06, P = 0.005) but demonstrated a statistically
      nonsignificant higher hazard for both renal end points (HR, 1.61; CI 0.19-13.89).
      Such lesions were also associated with a higher incidence of hypertension (149
      vs. 135 mm Hg) and greater proteinuria (2.7 vs. 1.9 g/day) at presentation. The
      use of the Oxford Classification did not aid decision-making with regard to the
      use of immunosuppression. Crescents and/or necrosis identified on histology were
      associated with the use of immunosuppression. Hence, there is a need for these
      lesions to be evaluated further in large cohorts and incorporated into future
      disease classifications.

PMID- 29657203
TI  - The development of malnutrition is not dependent on its traditional contributing
      factors in patients on maintenance hemodialysis in developing countries.
AB  - Malnutrition in dialysis population is associated with significant morbidity and
      mortality. Nutritional assessment is a neglected area in hemodialysis (HD)
      patients in developing countries. The aim of the study was to find out whether
      any traditional parameters have statistically significant correlation with
      malnutrition. All 58 end-stage renal disease patients on maintenance HD in our
      dialysis unit were enrolled in this cross-sectional study. The nutritional status
      was assessed by a predesigned questionnaire including subjective global
      assessment (SGA). Anthropometric measurements, peripheral neuropathy, and
      pertinent laboratory parameters were checked. The duration of HD ranged between
      three months to 10 years (mean 4 +/- 1.5 years). Of these 49 patients, 26 (53%)
      were males with a median age 45 (25-76) years. Fifteen patients (31%) were well
      nourished and 34 (69%) were undernourished including nine (19%) patients
      classified as severely malnourished according to SGA. Malnutrition appeared more
      prevalent in males, however, statistically not significant (P = 0.063). On
      univariate and multivariate analysis, no significance was found across well
      nourished and malnourished patients in terms of age, body mass index, calorie
      count, duration and frequency of dialysis, dry weight, interdialytic weight loss
      or gain in the past six months, body fat percentage, serum albumin, blood
      pressure, intradialytic hypotension, urea reduction ration, Kt/Vurea, peripheral
      neuropathy, and comorbidities. Psychosocial factors were identified in 24 (49%)
      patients with 19 (79%) having some degrees of malnutrition, but the finding did
      not reach the statistical significance. Surprisingly, the traditional factors
      studied in previous trials have not shown any significant association to
      malnutrition in our study based on the statistical analysis.

PMID- 29657204
TI  - Urinary tract infection in renal transplant recipients at a tertiary care center
      in India.
AB  - Our objective was to determine incidence, predisposing factors, and
      microbiological profile of urinary tract infection (UTI) in renal transplant
      recipients in our center. This was cross-sectional observational study, conducted
      at the Department of Nephrology, Army Hospital Research and Referral, Delhi,
      India. Two hundred and ten renal transplant recipients were studied over one
      year. Out of 210 transplant recipients, 69 (32.86%) had UTI. Majority (59/69) had
      undergone live renal transplantation and 10 cases had received cadaveric grafts.
      Forty-nine patients had primary infection while 20 patients had recurrences. The
      mean age of patients with UTI was 38.63 +/- 10 years. The incidence of UTI was
      higher in females (42.25%) than males (28.06%, P = 0.038). Majority of patients
      in younger age group (age <30 years) were female (58.82%). Males were
      predominantly affected in higher (>30 years) age group (61.54%). Most common
      causative agent was Escherichia coli (72.46%). Gram-negative bacilli accounted
      for 94.20% (65/69) while Gram-positive cocci for 5.8% (4/69) of positive
      cultures. Multidrug resistance was highest in Klebsiella pneumoniae (100%).
      Fifteen cases with UTI were detected to have underlying urinary tract
      abnormalities, most common being urethral stricture (60%). One patient was
      detected to have broken double J stent in the renal pelvis which led to recurrent
      E. coli infection. Forty-eight patients (69.57%) developed acute graft
      dysfunction secondary to UTI. Female sex (P = 0.038), urinary tract abnormality
      (P <0.01), prolonged Foley's catheterization (P <0.01), prolonged hospitalization
      after transplantation (P <0.01), new-onset diabetes after transplantation (P
      <0.01), and coexisting hepatitis C infection (P = 0.012) were statistically
      significant predisposing factors for UTI in renal transplant recipients.

PMID- 29657205
TI  - Evaluation and comparison of the effects of Xyla-P cream and cold compress on the
      pain caused by the cannulation of arteriovenous fistula in hemodialysis patients.
AB  - This study aimed to investigate and compare the effects of Xyla-P cream and cold
      compress on the pain caused by the insertion of a needle into the arteriovenous
      fistula (AVF) in hemodialysis (HD) patients. This clinical trial was conducted on
      HD patients who were selected using simple random sampling method. Using a visual
      analog scale, pain intensity was measured during two HD sessions in three stages
      including after the application of a placebo, after application of Xyla-P cream,
      and after the application of cold compress. The collected data were analyzed
      using descriptive statistics and repeated measures analysis of variance. Our
      results showed that there were statistically significant differences between the
      pain scores of the control group and Xyla-P cream group (P <0.001) and cold
      compress group (P <0.001) and between the pain scores of the Xyla-P cream group
      and cold compress group (P <0.001). The cannulation of an AVF causes moderate
      pain in HD patients. Cold compress is more effective than Xyla-P cream in
      reducing the intensity of the pain. Therefore, the nurses are recommended to use
      this pain relief method instead of medicinal methods.

PMID- 29657206
TI  - Comparison of intradermal route and dose of Hepatitis B vaccine administration in
      chronic dialysis patients: A pilot study.
AB  - We aimed to study the seroconversion rate in two arms of intradermal (ID) route:
      low dose with high-frequency and high dose with low-frequency hepatitis B (HB)
      vaccination in dialysis patients. A total of 56 patients, on either hemodialysis
      or peritoneal dialysis, were included. Patients were enrolled and randomized into
      two groups. The first group was immunized through the ID route and received
      weekly 10 MUg of vaccine at 0, 1, 2, 3, 4, 5, 6, and 7 weeks (low-dose with high
      frequency). The second group was immunized through the ID route and received two
      doses of 40 MUg at one-month interval (high dose with low frequency). Anti-HBs
      antibody titers were measured at one month and one month after completion of the
      vaccination, i.e., at three months in each group. At one month, each group had
      received 40 MUg of vaccine. The seroconversion rate was 28.57% in each group. At
      one month after completion of vaccination, seroconversion rate in low-dose ID and
      high-dose ID was 60% and 58.33%, respectively (P = 0.911) at 80 MUgm of total
      vaccine dose. The overall "good" responders in low-dose versus high-dose ID route
      were 30% and 50%, respectively (P = 0.179). However, among responders, anti-HBs
      antibody titers >=100 mIU/mL in low-dose and high-dose ID route were 50% and
      85.7%, respectively (P = 0.049). The rate of seroconversion is comparable in both
      low dose with high-frequency and high dose with low-frequency ID route.

PMID- 29657207
TI  - Adoption of transposed basilic vein as access for hemodialysis.
AB  - The fistula first initiative has rekindled interest in transposition of basilic
      vein (TBV) in preference to arteriovenous grafts (AVG). TBV is considered to have
      advantages over AVG. The aim of this study was to analyze the outcome of TBVs in
      our center comparing them to a historically matched group of patients who had
      AVG. Thirty-two patients who underwent TBV as a vascular access procedure in
      Derriford Hospital between January 2010 and October 2014 were included in the
      study. The historical control group comprised 31 patients who had AVG inserted in
      the upper arm between January 1999 and December 2010. Patients who had looped AVG
      were excluded from the study. The primary failure rates were 22% (7/32) and 16%
      (5/31) for TBV and AVG, respectively (P = 0.7500). AVGs were associated with a
      higher incidence of infection and steal syndrome, but the differences were not
      statistically significant (P = 0.286 and P = 0.286, respectively). Twenty-two
      interventions were undertaken in the TBV group compared to 18 in the AVG group.
      This study shows that adoption of TBV reduces the need for AVG. To improve TBV
      access maturation and survival, it is necessary to consider adopting a selection
      criteria based on findings on vessel mapping.

PMID- 29657208
TI  - Renal amyloidosis in ankylosing spondylitis: A monocentric study and review of
      literature.
AB  - Secondary renal amyloidosis (RA) is the most common type of renal involvement in
      ankylosing spondylitis (AS). We assessed the epidemiologic and clinico-biological
      profile of AS patients with RA, to analyze treatment modalities and prognostic
      aspects, and to determine predictive factors of RA during AS. This was a
      retrospective study including 13 cases of RA among 212 cases who presented with
      AS, during the period from 1978 to 2006. The median age of the patients at the
      time of diagnosing AS was 47 years (range: 19-67). There were 11 males and two
      females. RA onset was diagnosed after a mean follow-up of 144.6 months (range: 10
      505) from the AS diagnosis. We noted erosive peripheral arthritis, lumbar
      stiffness with bamboo spine, and coxitis in 23.1%, 76.9%, and 30.8% of cases,
      respectively. Nephrotic syndrome was found in eight patients (61.5%). At the time
      of diagnosing RA, six patients had renal failure. Amyloid deposits were
      histologically proven by salivary gland biopsy in six cases (46.1%) and by renal
      biopsy in seven cases (53.8%). Four patients received a long-course treatment
      with colchicine but with a good outcome only in two cases. In our series, AS was
      more severe among patients with RA. Four predictive factors of RA were
      identified: smoking (P = 0.04), erosive peripheral arthritis (P = 0.002), bamboo
      spine (P = 0.001), and biologic indicators of inflammation (P = 0.0001). High
      erythrocyte sedimentation rate was identified as the only independent risk factor
      of RA during AS (P = 0.0001). Renal function as well as urinalysis should be
      monitored at regular intervals to detect early renal involvement during AS.

PMID- 29657209
TI  - Spectrum of biopsy-proven renal diseases: A single center experience.
AB  - Kidney biopsy is one of the most important tools in the assessment of kidney
      disease as histopathological diagnosis promotes evidence-based practice in
      Nephrology. This study included 271 consecutive percutaneous kidney biopsies (145
      males and 126 females) performed at EMS Memorial Cooperative Hospital,
      Perinthalmanna, Kerala, India, from September 2009 to March 2016. Among the
      biopsy-proven renal diseases (BPRD), primary glomerular diseases (PGD) were the
      most common (77.78%) followed by secondary glomerular diseases (SGD) (12.22%) and
      tubulointerstitial diseases (10%). The IgA nephropathy (IgAN) was the most common
      PGD and majority had mesangial hypercellularity (M1) (93.54%), tubular atrophy
      (T1 or T2 68.25%), and the most common pattern was M1, E0, S0, and T1, suggesting
      that patients of Indian subcontinent have aggressive disease type, unlike western
      literature. The focal segmental glomerulosclerosis (FSGS) was the second most
      common PGD and the majority were of not otherwise specified type. FSGS,
      membranous nephropathy and minimal change disease were the three most common
      causes for PGD causing nephrotic syndrome. Diabetic nephropathy and lupus
      nephritis were the two most common biopsy-proven SGDs. Among the patients of
      diabetes mellitus who underwent renal biopsy with suspicion of nondiabetic renal
      disease (NDRD), 58.33% had NDRD, 16.67% had DN+ NDRD, and 26.67% had DN alone.
      This study shows the changing pattern BPRD in comparison to earlier studies. This
      study also confirms the aggressive nature of IgAN in Indian patients and
      underlines the importance of renal biopsy in patients of DM.

PMID- 29657210
TI  - Refusal of hemodialysis by hospitalized chronic kidney disease patients in
      Pakistan.
AB  - In Pakistan, patients with chronic kidney disease (CKD) are commonly diagnosed at
      a late stage. There is little information about the refusal of hemodialysis by
      hospitalized CKD patients who need hemodialysis (HD) and reasons for acceptance
      and refusal among these patients. All patients with Stage V CKD who had medical
      indications to undergo HD and were hospitalized at a tertiary care facility over
      a six-month period were invited to participate in this study. Patients were
      surveyed regarding acceptance or refusing of HD and reasons for their decisions.
      Demographic, socioeconomic, and clinical characteristics of patients were
      compared between patients who accepted or refused HD. A total of 125 patients
      were included in the study. The mean age of the patients was 47.9 +/-12.1 years.
      The mean duration of diagnosis of CKD was 2.5 +/- 0.6 months. Of all patients, 72
      (57.6%) agreed to do HD and 53 (42.4%) refused HD. Patients with arteriovenous
      fistula in place (27.1 vs. 9.1%, P 0.02) and those in the middle- or higher
      income group (64.4% vs. 38.6%, p = 0.03) were more willing to undergo HD. Trust
      in doctor's advice (86.1%) was the most common reason for acceptance of HD.
      Frequency of HD per week (52.8%), lifelong and permanent nature of HD (50.9%),
      advice by family members or friends (37.7%), perception of poor quality of life
      on HD (35.8%), and fear of HD needles and complications during HD (33.9%) were
      the most common reasons for refusal. Refusal of HD is common among hospitalized
      CKD patients with medical indications to undergo HD, especially in lower income
      group.

PMID- 29657211
TI  - Etiological profile of chronic kidney disease: A single-center retrospective
      hospital-based study.
AB  - Chronic kidney disease (CKD) is one of the leading causes of chronic diseases
      globally, with rising incidence and prevalence. It is a major risk factor for
      cerebrovascular disease and coronary artery disease, which are the main causes of
      death in this population. The etiology of CKD is varied. This study was performed
      to evaluate the various etiologies of CKD among patients presenting to the
      Department of Nephrology, Guwahati Medical College, a tertiary referral center. A
      total of 5718 CKD patients were evaluated to identify the cause of CKD. The most
      common cause was found to be diabetes mellitus in 42.2%, followed by chronic
      glomerulonephritis in 21.4%, hypertension in 19.5%, obstructive uropathy in 6.9%,
      chronic interstitial nephritis in 3.6%, and autosomal dominant polycystic kidney
      disease in 1.5% of the patients. Nearly 2.7% of the patients had CKD of unknown
      etiology. Most of the common causes of CKD are potentially treatable and
      initiating appropriate treatment early may prevent the development of CKD or
      progression to end-stage renal disease.

PMID- 29657212
TI  - Mortality in the elderly with acute kidney injury in an internal medicine
      department in Abidjan, Cote D'Ivoire.
AB  - Acute kidney injury (AKI) in the elderly is characterized by high mortality. The
      objective of this study is to identify the causes of death in the elderly with
      AKI. This is a prospective cohort study with a descriptive purpose which was
      carried out during the period from January 2009 to December 2014 in the
      Department of Nephrology-Internal Medicine of Treichville University Hospital.
      The diagnosis of AKI was made on the basis of serum creatinine (SCr) values
      determined during hospitalization, according to KDIGO classification. Our study
      involved 107 elderly aged 65 and older with AKI. The hospital mortality rate was
      46.7% (50/107). The average age of deceased patients was 71.8 +/- 7 years with
      extremes of 65 and 90 years. We observed a male predominance with a sex ratio
      (41/9) of 4.55. AKI on admission was in Stage 1 in 16% of cases, in Stage 2 in
      24%, and in Stage 3 in 60% cases. SCr was normal in 8%, the AKI was in Stage 1 in
      34% (P = 0.09), Stage 2 in 18% (P = 0.001), and Stage 3 in 40% (P = 0.0001). AKI
      in deceased patients was organic in 36% of cases, obstructive in 30%, and
      functional in 6%. The etiologies of AKI were infections (46%), cancer (18%),
      benign tumors of the urinary tract (12%), malignant hypertension (6%),
      decompensated heart disease (6%), and drugs (6%). The main causes of death were
      sepsis (28%), cardiovascular disease (22%), severe renal failure (20%), pelvic
      cancers (16%), and liver failure (12%). All patients with cancer (P = 0.001) or
      HIV infected (P = 0.009) died. Sixty-eight percent of deaths occurred the 1st
      week. Death was earlier by sepsis and cardiovascular disease than by cancer.
      Mortality is high in the elderly. The main causes of death were sepsis,
      cardiovascular disease, renal failure, pelvic cancer, and liver failure.

PMID- 29657213
TI  - Reactive perforating collagenosis: An important differential diagnosis in
      hemodialysis patients.
AB  - This is a case report of a 68-year-old hypertensive, diabetic woman who was on
      regular thrice weekly hemodialysis (HD). She presented with gradually worsening
      left lower limb pain and swelling. Clinical examination revealed significant
      edema over the left calf and ankle joint with significant calf tenderness.
      Extensive workup including magnetic resonance imaging of the lower limb and
      venous Doppler failed to show any significant abnormality. In view of developing
      papular lesions over the area, skin biopsy was performed, which finally confirmed
      reactive perforating collagenosis. This diagnosis ensured reassurance to the
      patient with halting of further extensive and probably expensive testing. Simple
      conservative management and symptomatic relief improved the pain over the next
      few days. This case report highlights the importance of keeping a wide
      differential for calf tenderness in diabetic HD patients and projects reactive
      perforating collagenosis as one of the important but frequently missed entities
      in such a scenario.

PMID- 29657215
TI  - Acute gastric dilatation in a patient with lupus nephritis: An uncommon
      presentation of lupus mesenteric vasculitis.
AB  - Abdominal symptoms are common in patients with lupus nephritis and are often
      attributed to drugs or uremia per se. Lupus mesenteric vasculitis (LMV) or lupus
      enteritis is a rare entity reported in patients with active systemic lupus
      erythematosus. It usually occurs in patients with a long-standing history of
      lupus with high disease activity. Usually, small bowel is predominantly affected.
      The stomach and rectum are spared in view of significant collateral circulation.
      Here, we describe an 18-year-old boy who presented with nephrotic syndrome
      without any extrarenal features of lupus. On subsequent evaluation, he was found
      to have active lupus nephritis. He developed acute gastric dilatation secondary
      to extensive LMV. Imaging showed an extensive involvement of gastrointestinal
      tract from the stomach to the sigmoid colon, sparing the rectum. To the best of
      our knowledge, this is the first report of LMV presenting as acute gastric
      dilatation.

PMID- 29657214
TI  - Kaposi's sarcoma in patients with membranous nephropathy.
AB  - Although the relationship between Kaposi's sarcoma (KS) and renal transplant has
      been well described, there are rare cases of KS concurrent with membranous
      glomerulonephritis or other glomerular diseases. In this report, a patient with
      membranous glomerulonephritis that accepted long-term prednisolone and
      cyclosporine immunosuppressive therapy developed skin KS. Withdrawal of
      immunosuppressive treatment resulted in the disappearance of KS.

PMID- 29657216
TI  - Colistin-induced myasthenic syndrome in a patient with end-stage renal disease.
AB  - With resurgence of multidrug resistance (MDR) bacteria and no new novel broad
      spectrum antibiotic in research pipeline, usage of older generation antibiotics,
      once discarded due to their toxicity profile are becoming popular again. Often
      these drugs are the only option left in managing MDR bacteria-related sepsis.
      Colistin is one of such antibiotic which is often used in recent times after
      decades of its avoidance due to its diverse toxicity profile. In this case
      report, we present a rare myasthenic syndrome like neuromuscular complication
      developed in a patient after receiving colistin for treatment of MDR Klebsiella
      related urosepsis.

PMID- 29657217
TI  - Systemic lupus erythematosus with Sjogren's syndrome and renal tubular acidosis
      presenting as nephrogenic diabetes insipidus.
AB  - Systemic lupus erythematosus (SLE) presenting as diabetes insipidus (DI) is a
      rare association; there is a case report of neurogenic DI in patients of SLE;
      however, SLE and nephrogenic DI has not been reported in literature. We present a
      case of SLE presenting as nephrogenic DI. We report a case who presented with DI
      (nephrogenic) and fulfilled criteria for SLE and Sjogren's syndrome with renal
      tubular acidosis.

PMID- 29657218
TI  - Rapidly progressive glomerulonephritis: A wild card manifestation of lupus
      nephritis.
AB  - A significant proportion of individuals with systemic lupus erythematosus (SLE)
      will have clinical or laboratory evidence of renal involvement at some point in
      the course of their disease. Lupus nephritis (LN) is one of the more important
      systemic manifestations of SLE and although progression to end-stage renal
      disease (ESRD) is not usually the norm, a significant minority of patients will
      do so, some in a rather dramatic fashion. It is in such instances that LN
      constitutes a true nephrologic emergency. Gratifyingly, it is rarely a silent
      emergency and heightened awareness amongst clinicians about its unpredictable
      course should lead to earlier recognition and intervention. For this reason, a
      case of LN presenting with historical and histologic evidence of chronic kidney
      disease and superimposed, acute acceleration of renal function decline, leading
      rapidly to ESRD is reported here. A brief review of the literature surrounding
      the pathophysiologic mechanisms, clinicopathologic characteristics and current
      therapeutic approaches to LN is subsequently explored.

PMID- 29657219
TI  - Paraneoplastic glomerulopathies associated with hematologic malignancies.
AB  - Paraneoplastic glomerulopathy (PG) includes a group of glomerular lesions that
      are not directly related to tumor burden, invasion, or metastasis, but induced by
      products from tumor cells such as hormones, growth factors, cytokines, and tumor
      antigens. PG was first described by Galloway in 1922, in which nephrotic syndrome
      (NS) secondary to Hodgkin's lymphoma was reported. They can present before, at
      the time of diagnosis, during remission, or at relapse of the hematological
      malignancies. We present three cases of paraneoplastic NS associated with
      hematological malignancies. Early diagnosis and treatment can alter prognosis of
      these patients. Paraneoplastic syndromes would remit only with proper treatment
      of the neoplasia.

PMID- 29657220
TI  - Complete remission of nephrotic syndrome secondary to amyloid a amyloidosis in
      patient with inactive Crohn's disease after treatment by infliximab.
AB  - Secondary amyloidosis Amyloid A (AA) is an infrequent but a severe complication
      of Crohn's disease (CD). This complication results from the activity of the
      underlying inflammation disease to form amyloid fibril deposits in tissues. We
      present a case of a 34-year-old female patient with CD treated by azathioprine
      with inactive disease for three years and who developed a nephrotic syndrome
      secondary to AA amyloidosis. The treatment by infliximab for one year leads to a
      complete remission of the nephrotic syndrome. In this case, this complication
      occurred while the patient was clinically well, with biological and endoscopic
      markers showing an inactive or only mildly active disease. Infliximab could be a
      useful tool for a successful treatment of amyloidosis secondary to CD.

PMID- 29657221
TI  - Unusual cause of crystalline nephropathy.
AB  - Adenine phosphoribosyltransferase deficiency is a rare, inherited autosomal
      recessive disease presenting with 2,8-dihydroxyadenine (DHA) urolithiasis, DHA
      nephropathy, and chronic kidney disease. The presence of DHA crystals in urine
      and renal biopsy is pathognomonic of the disease. We report a 23-year-old female
      with acute renal failure and nephrotic proteinuria. Urinalysis showed reddish
      brown, round crystals with dark outline, and central spicules consistent with 2,8
      DHA crystals. Renal biopsy showed membranous nephropathy and 2,8-DHA nephropathy.
      Our patient improved with liberal fluid intake, restriction of high adenine
      content foods, and oral xanthine dehydrogenase inhibitor febuxostat. Early
      diagnosis and initiation of treatment prevent renal complications.

PMID- 29657222
TI  - Management of Salmonella peritonitis in a patient on peritoneal dialysis without
      catheter removal.
AB  - Peritoneal dialysis (PD)-associated peritonitis is an important contributor to
      morbidity and mortality; Gram-positive bacteria constitute the most frequent
      associated pathogens (45%-60%) followed by Gram-negative bacteria (25%-40%) and
      fungal infection (3%-6%). Salmonella peritonitis is an extremely rare cause of
      peritonitis (0.15%). Peritonitis attributed to Salmonella has been reported only
      in four cases. Herewith, we report a 68-year-old Sudanese female who presented to
      our PD unit with abdominal pain and diarrhea and was diagnosed to have Salmonella
      peritonitis. She was managed without catheter removal. To our knowledge, the
      association between Salmonella peritonitis due to Salmonella enteritidis in a
      patient on PD managed without catheter removal has been reported in only one case
      previously.

PMID- 29657223
TI  - Distal renal tubular acidosis in Sjogren's syndrome.
AB  - Interstitial nephritis and immune complex-mediated glomerulonephritis are the two
      common renal manifestations of primary Sjogren's syndrome (SS). Here, we discuss
      three cases of primary SS where presenting manifestation was distal renal tubular
      acidosis. The possibility of an underlying autoimmune disorder should be
      considered in a patient presenting with distal tubular acidosis or recurrent
      hypokalemic periodic paralysis as treatment of primary disease improves the
      outcome of illness.

PMID- 29657224
TI  - Comparison between adjuvanted and nonadjuvanted influenza vaccination among
      patients undergoing hemodialysis: A cost-effectiveness analysis from Thailand.

PMID- 29657225
TI  - Cost-effectiveness analysis of common tuberculosis screening laboratory tests for
      hemodialysis patients: An analysis from tropical endemic country, Thailand.

PMID- 29657226
TI  - The association between apolipoprotein E polymorphism and diabetic nephropathy in
      Iranian patients.

PMID- 29657227
TI  - Author's reply.

PMID- 29657228
TI  - Human babesiosis, renal failure, and dialysis: A summary and comment on forgotten
      disease.

PMID- 29657229
TI  - Sunitinib therapy as a cause of diffuse digestive tract hemorrhage in end-stage
      renal disease patient.

PMID- 29657230
TI  - Renal failure in advanced cholangiocarcinoma: Magnitude.

PMID- 29657231
TI  - Tunnel use facilitates handling of ICR mice and decreases experimental variation.
AB  - We evaluated a handling method using tunnels to tame laboratory mice (ICR) in the
      context of animal welfare and ease of handling. During 1-week acclimation to
      handling and subsequent 1-week oral administration (once per day), voluntary
      interaction with the experimenter was much greater in mice handled by a tunnel
      compared to those picked up by the tail. According to a rating of the ease of
      handling laboratory mice, a tunnel facilitated mouse handling during acclimation
      to handling and oral gavage of saline compared to tail handling. In addition,
      mice handled by a tunnel showed less anxiety than mice handled by the tail in the
      open field test, but not in elevated plus maze. Calculation of experimental
      variation in behavioral tests, which were used to mimic pharmacological studies,
      suggested that mice handled by a tunnel exhibited the tendency of less variation
      compared to those picked up by the tail, in both groups that were
      intraperitoneally administered saline as placebo and diazepam as an active drug.
      Thus, tunnel use could be beneficial for improving animal welfare and facilitated
      handling of ICR mice in mouse studies.

PMID- 29657232
TI  - CRISPR/Cas9-mediated knock-in of the murine Y chromosomal Sry gene.
AB  - Mammalian zygote-mediated genome editing via the clustered regularly interspaced
      short palindromic repeats/CRISPR-associated endonuclease 9 (CRISPR/Cas9) system
      is widely used to generate genome-modified animals. This system allows for the
      production of loss-of-function mutations in various Y chromosome genes, including
      Sry, in mice. Here, we report the establishment of a CRISPR-Cas9-mediated knock
      in line of Flag-tag sequences into the Sry locus at the C-terminal coding end of
      the Y chromosome (YSry-flag). In the F1 and successive generations, all male pups
      carrying the YSry-flag chromosome had normal testis differentiation and proper
      spermatogenesis at maturity, enabling complete fertility and the production of
      viable offspring. To our knowledge, this study is the first to produce a stable
      Sry knock-in line at the C-terminal region, highlighting a novel approach for
      examining the significance of amino acid changes at the naive Sry locus in
      mammals.

PMID- 29657234
TI  - (+/-)-Terreinlactone A, a Pair of 3-Substituted delta-Lactone Enantiomers Derived
      from Terrein from the Fungus Aspergillus terreus.
AB  - Terreinlactone A (1a/1b), a pair of 3-substituted delta-lactone enantiomers, and
      terreinlactone B (2), a new biosynthetic intermediate of 1a/1b, were isolated
      from Aspergillus terreus, along with their biosynthetic precursor (+)-terrein (3)
      and (+)-isoterrein (4). Compounds 1a and 1b were separated by using a Daicel
      chiral-pak ASH column eluting with n-hexane-EtOH (80 : 20). The structures of
      1a/1b with absolute configurations were determined by comprehensive spectroscopic
      analyses and electronic circular dichroic (ECD) calculations. Terreinlactone A
      (1) represents the first example of 1,5-seco-terrein and a biogenetic pathway is
      proposed from the precursor terrein via the intermediated terreinlactone B (2).

PMID- 29657233
TI  - Reproductive technologies for the generation and maintenance of valuable animal
      strains.
AB  - Many types of mutant and genetically engineered strains have been produced in
      various animal species. Their numbers have dramatically increased in recent
      years, with new strains being rapidly produced using genome editing techniques.
      In the rat, it has been difficult to produce knockout and knock-in strains
      because the establishment of stem cells has been insufficient. However, a large
      number of knockout and knock-in strains can currently be produced using genome
      editing techniques, including zinc-finger nuclease (ZFN), transcription activator
      like effector nuclease (TALEN), and the clustered regularly interspaced short
      palindromic repeats (CRISPR) and CRISPR-associated protein 9 (Cas9) system.
      Microinjection technique has also contributed widely to the production of various
      kinds of genome edited animal strains. A novel electroporation method, the
      "Technique for Animal Knockout system by Electroporation (TAKE)" method, is a
      simple and highly efficient tool that has accelerated the production of new
      strains. Gamete preservation is extremely useful for maintaining large numbers of
      these valuable strains as genetic resources in the long term. These reproductive
      technologies, including microinjection, TAKE method, and gamete preservation,
      strongly support biomedical research and the bio-resource banking of animal
      models. In this review, we introduce the latest reproductive technologies used
      for the production of genetically engineered animals, especially rats, using
      genome editing techniques and the efficient maintenance of valuable strains as
      genetic resources. These technologies can also be applied to other laboratory
      animals, including mice, and domestic and wild animal species.

PMID- 29657235
TI  - Reduction in Door-to-Balloon Time with Training for Effective and Efficient
      Action in Medical Service-Better Process (TEAMS-BP) at a Community Hospital in
      Japan.
AB  - ST-elevation myocardial infarction (STEMI) is a fatal condition. Prompt primary
      percutaneous coronary intervention is associated with lower mortality. However,
      community hospitals in Japan lack human and medical resources, and implementation
      of the same strategies as those used in the USA, such as an on-call cardiologist
      at the hospital, to achieve a door-to-balloon time of <= 90 min appears
      particularly challenging. Therefore, we used Training for Effective and Efficient
      Action in Medical Service-Better Process (TEAMS-BP) to develop a new process and
      assessed its effectiveness in reducing door-to-balloon time. TEAMS-BP can
      optimize the process by making the best use of available materials, machines,
      facilities and manpower. All processes conducted by physicians, nurses,
      electrocardiogram technicians, radiological technologists, and clerical staff in
      the emergency room were reviewed, documented, and standardized using the four
      steps of TEAMS-BP. The following processes were implemented: setting time goals,
      calling an electrocardiogram technician beforehand, minimizing tasks before
      calling a cardiologist, confirming the checklist, and providing data feedback.
      Forty-four STEMI patients who were treated after TEAMS-BP implementation were
      compared with 58 who were treated before implementation. Median door-to-balloon,
      door-to-electrocardiogram and door-to-laboratory times were significantly reduced
      after TEAMS-BP implementation, decreasing from 106 to 82 min, 14 to 6 min, and 67
      to 45 min, respectively. In conclusion, implementation of TEAMS-BP improved the
      door-to-balloon time of STEMI cases without additional resources or costs
      incurred by the hospital. TEAMS-BP can be implemented by any hospital wishing to
      develop a new process that accommodates local working conditions.

PMID- 29657236
TI  - Black soldier fly (Hermetia illucens) larvae enhances immune activities and
      increases survivability of broiler chicks against experimental infection of
      Salmonella Gallinarum.
AB  - Black soldier fly (Hermetia illucens) larvae (BSFL) are rich in protein and have
      the potential to be used in animal feed. The aim of the present study was to
      determine the immunoprophylactic effect of BSFL against Salmonella Gallinarum in
      broiler chicks as an alternative feed additive. Results showed that BSFL improved
      body weight gain and increased frequency of CD4+ T lymphocyte, serum lysozyme
      activity, and spleen lymphocyte proliferation. Moreover, BSFL reinforced
      bacterial clearance and increased survivability of broiler chicks against S.
      Gallinarum. These data suggested that BSFL has prophylactic properties with
      stimulating non-specific immune responses, as well as reduced bacterial burden
      against S. Gallinarum.

PMID- 29657237
TI  - Management of sternal dislocation with and without surgery in cats: Owner
      assessed long-term follow-up of two clinical cases.
AB  - The aim of this paper is to report two cases of sternal dislocation (SD) in cats
      and the long-term outcomes with and without surgery. In a cat with poly
      traumatized SD (Case 1), mandibular, radial, and ulnar fractures were corrected
      first, and the SD was allowed to heal without intervention for 14 months.
      However, normal healing did not occur and sternal instability remained.
      Therefore, the SD was corrected surgically, and the cat recovered fully within 4
      weeks. In a cat with isolated SD (Case 2), surgery was performed, and normal
      posture and gait were regained after 5 weeks. Furthermore, in both cases, no
      postoperative complications were observed during follow-up. Therefore, surgical
      correction of SD in cats is recommended.

PMID- 29657238
TI  - The first report of terbinafine resistance Microsporum canis from a cat.
AB  - A 2-year-old, exotic shorthair cat presented with baldness and mild scaling on
      trunk that was confirmed as Microsporum canis (M. canis) infection by the
      following methods. Wood's lamp and trichogram were used to demonstrate fungal
      elements suggestive of dermatophytosis consistent with M. canis. Dermatophyte
      test medium (DTM) and polymerase chain reaction (PCR) were used for
      identification. E-test and broth microdilution test were then utilized to
      estimate antifungal minimal inhibitory concentrations (MICs) towards ITZ and TRF
      respectively. The strain was isolated from the patient and revealed TRF MIC >32
      ug/ml and ITZ MIC 0.023 ug/ml. Patient was cured of dermatophytosis with systemic
      ITZ.

PMID- 29657239
TI  - Application of a Fresh Decellularized Pulmonary Allograft for Pulmonary Valve
      Replacement in Japan.
AB  - BACKGROUND: Tissue engineering has advanced the technique of decellularization of
      the heart valve. The valve is reseeded with the patient's own cells after
      implantation with suppression of immunologic reactions. The same advantage has
      been reported for fresh decellularized heart valves, and more than 10 years of
      excellent outcomes have been achieved. We began performing such heart valve
      implantations in 2013 as part of a clinical study at Osaka University. We report
      our evaluation of the safety and efficacy of heart valve implantation.Methods and
      Results:Human pulmonary valves from the German Society for Tissue Transplantation
      (n=2) or from Japanese heart transplant recipient heart (n=4) were used to make
      decellularized heart valves; the decellularization process was the same as that
      used in Europe. Valves were implanted in 5 adults with pulmonary valve
      insufficiency after tetralogy of Fallot repair and in 1 infant with a double
      outlet right ventricle with pulmonary stenosis. Postoperative echocardiography
      and cardiac magnetic resonance imaging revealed that the valve and ventricular
      function were significantly improved and maintained postoperatively. CONCLUSIONS:
      Decellularized heart valves could be the new material used as artificial heart
      valves. Pulmonary allografts derived from the hearts of heart transplant
      recipients are considered to be useful material for decellularized heart valves.
      The application of this valve to Japanese clinical circumstances and using the
      hearts of heart transplant recipients is considered to be very significant.

PMID- 29657240
TI  - Associations of non-standard employment with cardiovascular risk factors:
      findings from nationwide cross-sectional studies in Japan.
AB  - This study aimed to examine the cross-sectional association of non-standard
      employment with cardiovascular disease risk factors. Five yr of data from the
      Comprehensive Survey of Living Conditions and National Health and Nutritional
      Survey were combined. We used logistic regression to examine the association of
      employment contract (non-standard [part-time, dispatched, or contract] vs.
      standard [full-time and permanent]) with eight cardiovascular disease risk
      factors among 1,636 men and 2,067 women aged 40-60 yr. There were significant
      associations between non-standard employment and cardiovascular disease risk
      factors such as current smoking among men (odds ratio [OR] 1.39; 95% confidential
      interval [CI], 1.13-1.86) and diabetes among women (OR 1.83; 95% CI, 1.10-3.09).
      Non-standard employment was associated with a few cardiovascular disease risk
      factors in this middle-aged cohort in Japan.

PMID- 29657241
TI  - Expression dynamics of self-renewal factors for spermatogonial stem cells in the
      mouse testis.
AB  - Glial cell line-derived neurotrophic factor (GDNF) and fibroblast growth factor 2
      (FGF2) are bona fide self-renewal factors for spermatogonial stem cells (SSCs).
      Although GDNF is indispensable for the maintenance of SSCs, the role of FGF2 in
      the testis remains to be elucidated. To clarify this, the expression dynamics and
      regulatory mechanisms of Fgf2 and Gdnf in the mouse testes were analyzed. It is
      well known that Sertoli cells express Gdnf, and its receptor is expressed in a
      subset of undifferentiated spermatogonia, including SSCs. However, we found that
      Fgf2 was mainly expressed in the germ cells and its receptors were expressed not
      only in the cultured spermatogonial cell line, but also in testicular somatic
      cells. Aging, hypophysectomy, retinoic acid treatment, and testicular injury
      induced distinct Fgf2 and Gdnf expression dynamics, suggesting a difference in
      the expression mechanism of Fgf2 and Gdnf in the testis. Such differences might
      cause a dynamic fluctuation of Gdnf/Fgf2 ratio depending on the
      intrinsic/extrinsic cues. Considering that FGF2-cultured spermatogonia exhibit
      more differentiated phenotype than those cultured with GDNF, FGF2 might play a
      role distinct from that of GDNF in the testis, despite the fact that both factors
      are self-renewal factor for SSC in vitro.

PMID- 29657242
TI  - Diagnosis-related group (DRG)-based case-mix funding system, a promising
      alternative for fee for service payment in China.
AB  - Fee for services (FFS) is the prevailing method of payment in most Chinese public
      hospitals. Under this retrospective payment system, medical care providers are
      paid based on medical services and tend to over-treat to maximize their income,
      thereby contributing to rising medical costs and uncontrollable health
      expenditures to a large extent. Payment reform needs to be promptly implemented
      to move to a prospective payment plan. The diagnosis-related group (DRG)-based
      case-mix payment system, with its superior efficiency and containment of costs,
      has garnered increased attention and it represents a promising alternative. This
      article briefly describes the DRG-based case-mix payment system, it comparatively
      analyzes differences between FFS and case-mix funding systems, and it describes
      the implementation of DRGs in China. China's social and economic conditions
      differ across regions, so establishment of a national payment standard will take
      time and involve difficulties. No single method of provider payment is perfect.
      Measures to monitor and minimize the negative ethical implications and unintended
      effects of a DRG-based case-mix payment system are essential to ensuring the
      lasting social benefits of payment reform in Chinese public hospitals.

PMID- 29657243
TI  - Distinct pattern of Th17/Treg cells in pregnant women with a history of
      unexplained recurrent spontaneous abortion.
AB  - The aim of the current study was to determine the pattern of immune cells and
      related functional molecules in peripheral blood and at the maternal-fetal
      interface in women with unexplained recurrent spontaneous abortion (URSA). In
      part I, 155 women were included and divided into four groups: non-pregnant
      controls with no history of URSA (NPCs), pregnant controls with no history of
      URSA (PCs), non-pregnant women with a history of URSA (NPUs), and pregnant women
      with a history of URSA (PUs). Venous blood samples were collected and analyzed.
      In part II, 35 subjects with URSA and 40 subjects in the early stage of normal
      pregnancy who chose to undergo an abortion were recruited. Samples of the decidua
      were collected, and the proportion of immune cells and the expression of related
      molecules were evaluated. Peripheral regulatory T cells (Treg cells) increased in
      PCs compared to NPCs, but in women with URSA the flux of Treg cells disappeared
      when pregnancy occurred. Levels of interleukin-10 (IL-10), cytotoxic T lymphocyte
      associated antigen 4 (CTLA-4), and IL-17 and the ratio of Th17/Treg cells in
      peripheral blood remained stable among the four groups. At the maternal-fetal
      interface, the percentage of Treg cells, the level of CTLA-4 of CD4+CD25+CD127lo
      cells and CD4+Foxp3+ cells were significantly lower in women with URSA compared
      to controls, respectively. Levels of transforming growth factor-beta1 (TGF-beta1)
      mRNA and protein in the decidua significantly decreased in URSA while levels of
      IL-6 and tumor necrosis factor-alpha (TNF-alpha) and the Th17/Treg ratio
      significantly increased. In conclusion, peripheral Treg cells did not increase in
      pregnant women with URSA. The decrease in Treg cells and levels of CTLA-4 and TGF
      beta1 and as well as the increase in levels of IL-6 and TNF-alpha, and the
      Th17/Treg ratio at the maternal-fetal interface might contribute to inappropriate
      maternal-fetal immune tolerance in URSA.

PMID- 29657244
TI  - Infiltration characteristics and influencing factors of retroperitoneal
      liposarcoma: Novel evidence for extended surgery and a tumor grading system.
AB  - This study sought to evaluate the infiltration tendency of retroperitoneal
      liposarcoma (RPLS) from a new pathological angle by exploring the infiltration
      characteristics, which could provide helpful information to facilitate surgical
      decision-making and prognosis prediction. Concurrently, we aim to identify
      significant indicators of infiltration. A total of 61 consecutive patients with
      RPLS at our institution were retrospectively analyzed. All patients received
      extended surgery. The tumor infiltration characteristics and influencing factors
      were studied based on the pathological diagnosis. Univariate and multivariate
      analyses of organ infiltration (OI) and surrounding fat infiltration (SFI) were
      performed. OI was found in 95 (28.5%) resected organs from 39 (60.7%) patients,
      and SFI was found in 119 (35.7%) resected organs from 47 (77%) patients. The
      tumor infiltrated the serosal layer of 13 organs (13/37, 35.1%), the muscularis
      layer of 18 organs (18/37, 48.6%) and the submucosa of 6 organs (6/37, 16.2%).
      The percentage of lipoblasts and the rates of necrosis and mitosis were all
      significantly higher in high-grade tumors (dedifferentiated, round cell, and
      pleomorphic). A high lipoblast percentage (>= 20%) was the only independent risk
      factor for OI. A recurrent tumor and a high-grade tumor were independent risk
      factors for SFI. In conclusion, RPLS has a high infiltration tendency, such that
      it frequently infiltrates organs and surrounding fat tissue. Therefore, extended
      resection of the tumor and the adjacent organs is recommended. The percentage of
      lipoblasts was associated with the tumor grade and infiltration characteristics;
      thus, lipoblast percentage may become a new grading factor for RPLS.

PMID- 29657245
TI  - Strengthening maternal and child health in China: Lessons from transforming
      policy proposals into action.
AB  - China has made impressive achievements in improving maternal and child health
      (MCH) over the past few decades. This paper uses a policy lens to examine reasons
      for these achievements as well as barriers to further success. We found that
      strong governmental commitment and leadership, effective coordination, proactive
      participation of different stakeholders, and the provision of adequate resources
      were associated with China's success in improving MCH outcomes. Other low- and
      middle-income countries can learn valuable lessons from China's experience. These
      lessons include i) prioritizing MCH on the national development agenda, ii)
      keeping national ownership over health development cooperation, and iii)
      establishing effective monitoring, evaluation and accountability mechanisms for
      MCH programs.

PMID- 29657246
TI  - Effects of three forms of local anesthesia on perioperative fentanyl-induced
      hyperalgesia.
AB  - Both local infiltration analgesia (LIA) and nerve block are common analgesic
      modalities for pain relief after surgery. The aim of the current study was to
      investigate the effects of those two modalities on pain behavior and the
      expression of pro-inflammatory cytokines such as interleukin (IL)-1beta and IL-6
      and tumor necrosis factor-alpha (TNF-alpha) in the spinal cord and dorsal root
      ganglion (DRG) in a rat model of perioperative fentanyl induced hyperalgesia.
      Rats were injected with fentanyl (60 MUg/kg) 4 times and received a plantar
      incision after the second injection or they received pre-incision LIA and sciatic
      nerve block (SNB) or post-incision LIA with levobupivacaine (0.5%, 0.2 mL).
      Mechanical and thermal nociceptive thresholds were assessed using the tail
      pressure test and paw withdrawal test on the day before drug injection, 1 and 4
      hours after injection, and 1-7 days later. The lumbar spinal cord and dorsal root
      ganglia were collected from rats in each group to measure IL-1beta, IL-6, and TNF
      alpha on the day before drug injection, 4 hours after injection, and 1, 3, 5, and
      7 days later. Fentanyl and an incision induced a significantly delayed mechanical
      hyperalgesia in the tail and thermal hyperalgesia in both hind paws and up
      regulation of pro-inflammatory cytokines in the spinal cord and dorsal root
      ganglia. Rats treated with pre-incision LIA and SNB or post-incision LIA had
      alleviated hyperalgesia and significantly reduced levels of IL-1beta, IL-6, and
      TNF-alpha compared to the control group. LIA and SNB partly prevented
      perioperative fentanyl-induced hyperalgesia and up-regulation of pro-inflammatory
      cytokines in the spinal cord and dorsal root ganglia.

PMID- 29657247
TI  - Protective Effect of Taohong Siwu Decoction on Abnormal Uterine Bleeding Induced
      by Incomplete Medical Abortion in Rats during Early Pregnancy.
AB  - Abnormal uterine bleeding (AUB) induced by incomplete abortion is a common
      gynecological disease. Taohong Siwu decoction (TSD) is a traditional Chinese
      medicine (TCM) formula, which has been developed to treat AUB for hundreds of
      years. In this study, rats had incomplete abortion induced in early pregnancy
      using mifepristone and misoprostol. The duration and quantity of uterine bleeding
      were recorded and measured. The pathologic histologic grade was evaluated by
      hematoxylin-eosin staining (HE). Estradiol (E2) and progesterone (P) levels were
      measured by enzyme linked immunosorbent assays (ELISA). The expression levels of
      estrogen receptor alpha (ERalpha) and progesterone receptor (PR) were detected by
      immunohistochemistry and Western blotting analysis. We demonstrated that TSD
      significantly reduced the duration and quantity of uterine bleeding. Meanwhile,
      TSD promoted endometrial repair and significantly up-regulated the E2 levels and
      the ERalpha expression. These results suggest that TSD have a protective effect
      on the uteri; the mechanism may be concerned with up-regulation of the levels of
      E2 and the ERalpha expression.

PMID- 29657248
TI  - Association of fat mass and obesity-associated and retinitis pigmentosa guanosine
      triphosphatase (GTPase) regulator-interacting protein-1 like polymorphisms with
      body mass index in Chinese women.
AB  - Body mass index (BMI) is the most commonly used quantitative measure of
      adiposity. It is a kind of complex genetic diseases which are caused by multiple
      susceptibility genes. The first intron of fat mass and obesity-associated (FTO)
      has been widely discovered to be associated with BMI. Retinitis pigmentosa GTPase
      regulator-interacting protein-1 like (RPGRIP1L) is located in the upstream region
      of FTO and has been proved to be linked with obesity through functional tests. We
      carried out a genetic association analysis to figure out the role of the FTO gene
      and the RPGRIP1L gene in BMI. A quantitative traits study with 6,102 Chinese
      female samples, adjusted for age, was performed during our project. Among the
      twelve SNPs, rs1421085, rs1558902, rs17817449, rs8050136, rs9939609, rs7202296,
      rs56137030, rs9930506 and rs12149832 in the FTO gene were significantly
      associated with BMI after Bonferroni correction. Meanwhile, rs9934800 in the
      RPGRIP1L gene showed significance with BMI before Bonferroni correction, but this
      association was eliminated after Bonferroni correction. Our results suggested
      that genetic variants in the FTO gene were strongly associated with BMI in
      Chinese women, which may serve as targets of pharmaceutical research and
      development concerning BMI. Meanwhile, we didn't found the significant
      association between RPGRIP1L and BMI in Chinese women.

PMID- 29657250
TI  - TGFbeta1-induced Amelotin gene expression is downregulated by Bax expression in
      mouse gingival epithelial cells.
AB  - Amelotin (AMTN) is induced upon initiation of apoptosis by transforming growth
      factor beta1 (TGFbeta1) and is mediated by Smad3 in gingival epithelial cells
      (GE1 cells). This upregulation of AMTN gene expression is temporary, and the
      mechanism responsible is still unclear. The present study investigated the
      transcriptional downregulation of TGFbeta1-induced AMTN gene expression in GE1
      cells during the progression of apoptosis. To examine time-dependent changes in
      the levels of AMTN, Smad3 and Bax mRNA induced by TGFbeta1, real-time PCR
      analyses were performed. Immunocytochemistry was carried out to detect the
      expression of Smad3 and Bax. Transient transfection analyses were performed using
      mouse AMTN gene promoter constructs of various lengths including Smad response
      elements (SBEs), in the presence or absence of TGFbeta1. Changes in Smad3 binding
      to SBEs resulting from overexpression of Bax were examined using ChIP assays.
      Overexpression of Bax dramatically downregulated the levels of TGFbeta1-induced
      AMTN mRNA and transcription of the AMTN gene. Smad3 binding to SBEs in the mouse
      AMTN gene promoter was induced by overexpression of Smad3 or TGFbeta1, and this
      was inhibited by Bax overexpression. These results show that the levels of AMTN
      mRNA induced by TGFbeta1 and Smad3 are decreased by robust expression of Bax in
      gingival epithelial cells.

PMID- 29657249
TI  - Microcomputed tomographic evaluation of techniques for warm gutta-percha
      obturation.
AB  - Transparent epoxy resin root canal models were used to evaluate vertical
      condensation techniques for obturating lateral canals. The root canal model was
      configured with a straight main root canal and four right-angled lateral canals
      at 1.0 and 3.0 mm from the apex. Root canal obturation was performed with
      Thermafil, Obtura II, or NT condenser. Obturation volume in lateral canals was
      measured by three-dimensional microcomputed tomography, and one-way analysis of
      variance was used to analyze differences between groups. Lateral canals at 1.0
      and 3.0 mm were uniformly filled by all obturation methods. Among the three
      obturation methods, Thermafil resulted in the highest obturation volumes for all
      lateral canals.

PMID- 29657251
TI  - Laminin-1 acts as an adhesive for odontoblast-like cells and promotes their
      differentiation toward a hard tissue-forming phenotype.
AB  - The present study was designed to investigate the effect of laminin-1 (LN-1 or LN
      111) on an odontoblast-like cell line, MDPC-23. Wells of non-treated polystyrene
      plates were coated with various concentrations of LN-1 (0.1, 1, 10, and 100
      ug/mL) and left to dry for 2 days. Water-coated surfaces were used as controls.
      MDPC-23 cell proliferation, differentiation and mineralization were evaluated in
      terms of the CCK-8 assay, ALP activity, real-time RT-PCR and Alizarin red
      staining. The data indicated that LN-1 promoted the proliferation of MDPC-23
      cells in a concentration-dependent manner. Moreover, it enhanced ALP activity and
      expression of key odontogenic genes (DMP-1 and DSPP) upon addition of
      mineralization reagents, leading to significant promotion of calcification by the
      cells. These results demonstrate that LN-1 acts as an adhesive for odontoblast
      like cells, allowing up-regulation of odontogenic genes and accelerating matrix
      mineralization. In the context of the present study, the optimal LN-1 coating
      concentration for MDPC-23 cells was suggested to be 100 ug/mL.

PMID- 29657252
TI  - Periprocedural Complications in Patients Undergoing Catheter Ablation of Atrial
      Fibrillation Without Discontinuation of a Vitamin K Antagonist and Direct Oral
      Anticoagulants.
AB  - BACKGROUND: Periprocedural anticoagulation is important in catheter ablation (CA)
      of atrial fibrillation (AF) and there is increasing evidence that uninterrupted
      vitamin K antagonist (VKA) therapy is superior to interrupted anticoagulation
      strategies. Since the emergence of direct oral anticoagulants (DOACs), numerous
      studies have shown promising results for their use in uninterrupted strategies.
      However, further studies are needed to further define the efficacy and safety of
      performing AF ablation with uninterrupted factor XA inhibitors or direct thrombin
      inhibitors.Methods and Results:We have performed CA of AF without discontinuation
      of either VKA or DOAC therapy since April 2014. A total of 376 patients with AF
      underwent CA including pulmonary vein isolation. All of the patients were divided
      into 2 groups (uninterrupted VKA or uninterrupted DOACs). Anticoagulation with
      DOACs was associated with fewer complications than uninterrupted VKA therapy
      (P=0.04). There were significant differences between groups in the rates of
      congestive heart failure, left ventricular ejection fraction, body weight, and
      estimated glomerular filtration rate and of the CHADS2, CHA2DS2-VASc and HAS-BLED
      scores. Therefore, we also analyzed the results using the propensity score
      matching method. We found no significant difference in periprocedural
      complications between uninterrupted VKA or DOACs therapy (P=0.65). CONCLUSIONS:
      CA of AF without discontinuation of DOACs is not inferior to CA without
      discontinuation of a VKA, with regard to ischemic or hemorrhagic complications.

PMID- 29657253
TI  - Minimally Invasive Mitral Valve Repair Through Right Minithoracotomy - 11-Year
      Single Institute Experience.
AB  - BACKGROUND: Although minimally invasive mitral valve repair (MIMVR) is
      increasingly being performed, only a few clinical studies from Japanese
      institutions have been reported.Methods and Results:From 2006 to 2017, 387
      consecutive patients (135 females, mean age 56+/-13 years) underwent an initial
      isolated MIMVR through a right minithoracotomy. The mitral etiology was
      degenerative in 348, functional in 22, and endocarditis in 13 cases. Repair
      techniques included leaflet resection/plication in 280, chordal reconstruction in
      109, and annuloplasty alone in 24 patients, and concomitant procedures included
      tricuspid valve repair and atrial fibrillation ablation in 70 (18.1%) and 78
      (20.2%), respectively. Hospital mortality rate was 0.26%; 2 patients (0.5%)
      required intraoperative conversion to a median sternotomy. Perioperative
      morbidity included stroke (1.3%), reoperation for bleeding (0.8%), prolonged
      ventilation (0.5%), and permanent pacemaker implantation (2.1%). The transfusion
      rate was 14.7% and median ventilation time was 4 hours. Overall 5-year survival
      was 96.9%. For patients with degenerative mitral regurgitation (MR), the 5-year
      freedom from reoperation or severe recurrent MR, and freedom from >=moderate MR
      were 94.7% and 82.2%, respectively. Repair for anterior mitral leaflet prolapse
      and the initial 30 cases were associated with higher occurrence of recurrent MR.
      CONCLUSIONS: MIMVR can be performed safely with low levels of mortality and
      morbidity, and provides sufficient repair durability. A learning curve exists in
      terms of repair durability, especially for anterior mitral leaflet repair.

PMID- 29657254
TI  - Are All New-Generation Drug-Eluting Stents Equal? - Long-Term Follow-up Is
      Necessary.

PMID- 29657255
TI  - Genome-wide siRNA screening in mouse bone marrow-derived macrophages revealed
      that knockdown of ribosomal proteins suppresses IL-10 and enhances TNF-alpha
      production.
AB  - Macrophages play a central role in the immune response, and their diverse
      functions are attributed to the spectrum of their functional states. To elucidate
      molecules involved in modulating the balance between the anti-inflammatory
      cytokine IL-10 and the pro-inflammatory cytokine TNF-alpha, we conducted genome
      wide siRNA screening. First, we established an siRNA screening system using mouse
      bone marrow-derived macrophages, which are a suitable model for studying
      functional states of macrophages in vitro. In the primary screen and the
      subsequent reproducibility assay, 112 siRNA pools demonstrated enhancement of IL
      10 production and 497 siRNA pools suppressed IL-10 production. After a
      deconvolution assay for IL-10-up-regulating siRNA pools, 8 genes were identified
      as IL-10 repressors, including Cnot1 and Rc3h1, components of the CCR4-NOT
      complex known to degrade cytokine mRNAs. On the other hand, siRNA pools targeting
      ribosomal proteins were frequently found among those that down-regulated IL-10
      production and up-regulated TNF-alpha production. Four pools were assayed using
      deconvoluted siRNAs and identified as high-confidence hits. Thus, we found that
      the genome-wide knockdown of 19 ribosomal proteins resulted in decreased IL-10
      and increased TNF-alpha production.

PMID- 29657256
TI  - Colonal monomorphic epitheliotropic intestinal T-cell lymphoma with novel
      phenotype of cytoplasmic CD3 expression.
AB  - Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a new clinical
      entity that was reclassified from enteropathy-associated T-cell lymphoma in the
      2016 WHO classification. An 83-year-old man with fever and diarrhea was referred
      to our hospital because of free air in the abdominal cavity and wall thickening
      of the large intestine on CT. Colonofiberscopic examination revealed mucosal
      edema and multiple ulcers at the sigmoid colon, splenic flexure, and transverse
      colon. Histopathological examination of the mucosal biopsy specimen demonstrated
      dense infiltration of small lymphocytes with nuclear atypia, some of which
      exhibited intraepithelial invasion. Immunohistologically, these lymphocytes were
      positive for CD3, CD56, and perforin. Regarding CD3 expression, the antigen was
      found to only be expressed in the cytoplasm and not on the surface membrane on
      flow cytometric analysis. PCR examination of the T-cell receptor (TCR) gene
      revealed monoclonal gene rearrangements of TCR-gamma and TCR-beta. Based on these
      findings, a diagnosis of colonal MEITL with cyCD3 expression at Lugano clinical
      stage 1 was made. After conservative management of the peritonitis, we treated
      the patient with CHOP and DeVIC regimens, but he developed progressive disease
      and died. The cyCD3 expression in MEITL may be novel, suggesting a thymocyte
      origin of the tumor cells.

PMID- 29657257
TI  - The Gradual Shift of Overweight, Obesity, and Abdominal Obesity Towards the Poor
      in a Multi-ethnic Developing Country: Findings From the Malaysian National Health
      and Morbidity Surveys.
AB  - BACKGROUND: Economic development is known to shift the distribution of obesity
      from the socioeconomically more advantaged to the less advantaged. We assessed
      the socioeconomic trends in overweight, obesity, and abdominal obesity across a
      period of significant economic growth. METHODS: We used the Malaysian National
      Health and Morbidity Survey data sets for the years 1996, 2006, and 2011 to
      analyze the trends among adults aged 30 years and above. The World Health
      Organization's Asian body mass index cut-off points of >=23.0 kg/m2 and >=27.5
      kg/m2 were used to define overweight and obesity, respectively. Abdominal obesity
      was defined as having a waist circumference of >=90 cm for men and >=80 cm for
      women. Household per-capita income was used as a measure of socioeconomic
      position. As a summary measure of inequality, we computed the concentration
      index. RESULTS: Women in Peninsular Malaysia demonstrated patterns that were
      similar to that of developed countries in which the distributions for overweight,
      obesity, and abdominal obesity became concentrated among the poor. For women in
      East Malaysia, distributions became neither concentrated among the rich nor poor,
      while distributions for men were still concentrated among the rich. Chinese
      women, particularly from the richest quintile, had the lowest rates and lowest
      increase in overweight and obesity. All distributions of Chinese women were
      concentrated among the poor. The distributions of Malay men were still
      concentrated among the rich, while distributions for Chinese and Indian men and
      Malay and Indian women were neither concentrated among the rich nor poor.
      CONCLUSION: As the country continues to progress, increasing risks of overweight
      and obesity among the socioeconomically less advantaged is expected.

PMID- 29657258
TI  - Heat-Not-Burn Tobacco Products Are Getting Hot in Italy.

PMID- 29657259
TI  - The Ins and Outs of miRNA-Mediated Gene Silencing during Neuronal Synaptic
      Plasticity.
AB  - Neuronal connections through specialized junctions, known as synapses, create
      circuits that underlie brain function. Synaptic plasticity, i.e., structural and
      functional changes to synapses, occurs in response to neuronal activity and is a
      critical regulator of various nervous system functions, including long-term
      memory formation. The discovery of mRNAs, miRNAs, ncRNAs, ribosomes,
      translational repressors, and other RNA binding proteins in dendritic spines
      allows individual synapses to alter their synaptic strength rapidly through
      regulation of local protein synthesis in response to different physiological
      stimuli. In this review, we discuss our understanding of a number of miRNAs,
      ncRNAs, and RNA binding proteins that are emerging as important regulators of
      synaptic plasticity, which play a critical role in memory, learning, and diseases
      that arise when neuronal circuits are impaired.

PMID- 29657260
TI  - Are We Eating Our Way to Prostate Cancer-A Hypothesis Based on the Evolution,
      Bioaccumulation, and Interspecific Transfer of miR-150.
AB  - MicroRNAs (miRNAs) are well established epigenetic modifiers. There is a lot of
      work being done to identify the evolutionary transfer of miRNAs both at intra-
      and interspecific levels. In this hypothesis-driven review, we have suggested a
      possible reason as to why miR-150 can be a promising diagnostic biomarker for
      prostate cancer using theories of evolution, bio-accumulation, and interspecific
      transfer of miRNAs.

PMID- 29657261
TI  - Micro-RNA Feedback Loops Modulating the Calcineurin/NFAT Signaling Pathway.
AB  - Nuclear factor of activated T cells (NFAT) is a family of transcription factors
      important for innate and adaptive immune responses. NFAT activation is tightly
      regulated through the calcineurin/NFAT signaling pathway. There is increasing
      evidence on non-coding RNAs such as miRNAs playing a crucial role in regulating
      transcription factors and signaling pathways. However, not much is known about
      microRNAs (miRNAs) targeting the calcineurin/NFAT signaling pathway involved in
      immune response in human. In this study, a comprehensive pathway level analysis
      has been carried out to identify miRNAs regulating the calcineurin/NFAT signaling
      pathway. Firstly, by incorporating experimental data and computational
      predictions, 191 unique miRNAs were identified to be targeting the
      calcineurin/NFAT signaling pathway in humans. Secondly, combining miRNA
      expression data from activated T cells and computational predictions, 32 miRNAs
      were observed to be induced by NFAT transcription factors. Finally, 11 miRNAs
      were identified to be involved in a feedback loop to modulate the
      calcineurin/NFAT signaling pathway activity. This data demonstrate the potential
      role of miRNAs as regulators of the calcineurin/NFAT signaling pathway. The
      present study thus emphasizes the importance of pathway level analysis to
      identify miRNAs and understands their role in modulating signaling pathways and
      transcription factor activity.

PMID- 29657262
TI  - HDAC Inhibition in Vascular Endothelial Cells Regulates the Expression of ncRNAs.
AB  - While clinical and pre-clinical trials indicate efficacy of histone deacetylase
      (HDAC) inhibitors in disease mediated by dynamic lysine modification, the impact
      on the expression of non-coding RNAs (ncRNAs) remains poorly understood. In this
      study, we investigate high throughput RNA sequencing data derived from primary
      human endothelial cells stimulated with HDAC inhibitors suberanilohydroxamic acid
      (SAHA) and Trichostatin A (TSA). We observe robust regulation of ncRNA
      expression. Integration of gene expression data with histone 3 lysine 9 and 14
      acetylation (H3K9/14ac) and histone 3 lysine 4 trimethylation (H3K4me3) datasets
      identified complex and class-specific expression of ncRNAs. We show that EP300
      target genes are subject to histone deacetylation at their promoter following
      HDAC inhibition. This deacetylation drives suppression of protein-coding genes.
      However, long intergenic non-coding RNAs (lincRNAs) regulated by EP300 are
      activated following HDAC inhibition, despite histone deacetylation. This
      increased expression was driven by increased H3K4me3 at the gene promoter. For
      example, elevated promoter H3K4me3 increased lincRNA MALAT1 expression despite
      broad EP300-associated histone deacetylation. In conclusion, we show that HDAC
      inhibitors regulate the expression of ncRNA by complex and class-specific
      epigenetic mechanisms.

PMID- 29657263
TI  - Circulating microRNAs as Prognostic and Predictive Biomarkers in Patients with
      Colorectal Cancer.
AB  - MiRNAs are suggested as promising cancer biomarkers. They are stable and
      extractable from a variety of clinical tissue specimens (fresh frozen or formalin
      fixed paraffin embedded tissue) and a variety of body fluids (e.g., blood, urine,
      saliva). However, there are several challenges that need to be solved,
      considering their potential as biomarkers in cancer, such as lack of consistency
      between biomarker panels in independent studies due to lack of standardized
      sample handling and processing, use of inconsistent normalization approaches, and
      differences in patients populations. Focusing on colorectal cancer (CRC),
      divergent results regarding circulating miRNAs as prognostic or predictive
      biomarkers are reported in the literature. In the present review, we summarize
      the current data on circulating miRNAs as prognostic/predictive biomarkers in
      patients with localized and metastatic CRC (mCRC).

PMID- 29657264
TI  - Correction: Vaidyanathan et al. Are We Eating Our Way to Prostate Cancer-A
      Hypothesis Based on the Evolution, Bioaccumulation, and Interspecific Transfer of
      miR-150. Non-Coding RNA 2016, 2, 2.
AB  - The authors wish to make the following correction to this paper [1].[...].

PMID- 29657265
TI  - Promoter-Associated RNAs Regulate HSPC152 Gene Expression in Malignant Melanoma.
AB  - The threshold of 200 nucleotides (nt) conventionally divides non-coding RNAs
      (ncRNA) into long ncRNA (lincRNA, that have more than 200 nt in length) and the
      remaining ones which are grouped as "small" RNAs (microRNAs, small nucleolar RNAs
      and piwiRNAs). Promoter-associated RNAs (paRNAs) are generally 200-500 nt long
      and are transcribed from sequences positioned in the promoter regions of genes.
      Growing evidence suggests that paRNAs play a crucial role in controlling gene
      transcription. Here, we used deep sequencing to identify paRNA sequences that
      show altered expression in a melanoma cell line compared to normal melanocytes.
      Thousands of reads were mapped to transcription start site (TSS) regions. We
      limited our search to paRNAs adjacent to genes with an expression that differed
      between melanoma and normal melanocytes and a length of 200-500 nt that did not
      overlap the gene mRNA by more than 300 nt, ultimately leaving us with 11 such
      transcripts. Using quantitative real-time PCR (qRT-PCR), we found a significant
      correlation between the expression of the mRNA and its corresponding paRNA for
      two studied genes: TYR and HSPC152. Ectopic overexpression of the paRNA of
      HSPC152 (designated paHSPC) enhanced the expression of the HSPC152 mRNA, and an
      siRNA targeting the paHSPC152 decreased the expression of the HSPC152 mRNA.
      Overexpression of paHSPC also affected the epigenetic structure of its putative
      promoter region along with effects on several biologic features of melanoma
      cells. The ectopic expression of the paRNA to TYR did not have any effect.
      Overall, our work indicates that paRNAs may serve as an additional layer in the
      regulation of gene expression in melanoma, thus meriting further investigation.

PMID- 29657266
TI  - Argonaute 2 Expression Correlates with a Luminal B Breast Cancer Subtype and
      Induces Estrogen Receptor Alpha Isoform Variation.
AB  - Estrogen receptor alpha (ERalpha) signaling pathways are frequently disrupted in
      breast cancer and contribute to disease progression. ERalpha signaling is
      multifaceted and many ERalpha regulators have been identified including
      transcription factors and growth factor pathways. More recently, microRNAs
      (miRNAs) are shown to deregulate ERalpha activity in breast carcinomas, with
      alterations in both ERalpha and miRNA expression correlating to cancer
      progression. In this study, we show that a high expression of Argonaute 2 (AGO2),
      a translation regulatory protein and mediator of miRNA function, correlates with
      the luminal B breast cancer subtype. We further demonstrate that a high
      expression of AGO2 in ERalpha+ tumors correlates with a poor clinical outcome.
      MCF-7 breast cancer cells overexpressing AGO2 (MCF7-AGO2) altered ERalpha
      downstream signaling and selective ERalpha variant expression. Enhanced ERalpha
      36, a 36 kDa ERalpha isoform, protein and gene expression was observed in vitro.
      Through quantitative polymerase chain reaction (qPCR), we demonstrate decreased
      basal expression of the full-length ERalpha and progesterone receptor genes, in
      addition to loss of estrogen stimulated gene expression in vitro. Despite the
      loss, MCF-7-AGO2 cells demonstrated increased estrogen stimulated tumorigenesis
      in vivo. Together with our clinical findings on AGO2 expression and the luminal B
      subtype, we suggest that AGO2 is a regulator of altered ERalpha signaling in
      breast tumors.

PMID- 29657267
TI  - The Non-Coding RNA Journal Club: Highlights on Recent Papers-4.
AB  - We are glad to share with you our fourth Journal Club and highlight some of the
      most interesting papers published recently.[...].

PMID- 29657268
TI  - Regulation of the U3-, U8-, and U13snoRNA Expression by the DEAD Box Proteins
      Ddx5/Ddx17 with Consequences for Cell Proliferation and Survival.
AB  - Small nucleolar RNAs (snoRNAs) in cooperation with their associated proteins
      (snoRNPs) contribute to the maturation of ribosomal RNA, transfer RNA, and other
      transcripts. Most snoRNPs mediate chemical base modifications of their RNA
      substrates, and a few others, like those formed by the C/D snoRNAs U3, U8, and
      U13, are needed for the structural organization and maturation of primary
      transcripts. The U3-, U8-, and U13snoRNAs are encoded by autonomous genes, and
      our knowledge about their expression regulation is limited. In this study, a
      significant increase in the concentrations of U3-, U8-, and U13snoRNA after a
      knockdown of DEAD box proteins Ddx5/Ddx17 in HeLa cells is observed. These
      alterations are shown to be caused by transcriptional suppression mediated by
      Ddx5/Ddx17 via histone deacetylase 1 in a promoter-dependent way. The biological
      function of this expression control may be related to the role of Ddx5/Ddx17 in
      cell proliferation. The U3snoRNA is shown here to be essential for the
      proliferation and viability of human cells. Moreover, it was found that U3snoRNA
      interacts with Argonaute 2 in the RNA-induced silencing complexes (RISC),
      pointing to a microRNA-like function. For this reason, the 3' untranslated region
      of the A-kinase anchor protein 9 (AKAP9)-mRNA could be identified as a potential
      target.

PMID- 29657269
TI  - Erratum: The Non-Coding RNA Journal Club: Highlights on Recent Papers-4. Non
      Coding RNA 2016, 2, 9.
AB  - Please note that in the published editorial [1], affiliations 1, and 8 contained
      errors.[...].

PMID- 29657270
TI  - TWEAK Negatively Regulates Human Dicer.
AB  - The ribonuclease Dicer plays a central role in the microRNA pathway by processing
      microRNA precursors (pre-microRNAs) into microRNAs, a class of 19- to 24
      nucleotide non-coding RNAs that regulate expression of ~60% of the genes in
      humans. To gain further insights into the function and regulation of Dicer in
      human cells, we performed a yeast two-hybrid (Y2HB) screen using human Dicer
      double-stranded RNA-binding domain (dsRBD) as bait. This approach identified
      tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) as a Dicer
      interacting protein candidate. Confocal immunofluorescence microscopy revealed
      the colocalization of Dicer and TWEAK proteins at the perinuclear region of HeLa
      cells. The Dicer-TWEAK protein interaction was confirmed by coimmunoprecipitation
      and found not likely to be mediated by RNA. TWEAK dose-dependently reduced pre
      microRNA conversion into mature microRNA in Dicer activity assays using extracts
      of transfected human HEK 293 cells. TWEAK expression also impaired microRNA
      guided RNA silencing of a reporter gene induced by a pre-microRNA. These findings
      suggest a role for TWEAK-a pro-inflammatory cytokine-in regulating Dicer function
      and microRNA biogenesis, and its possible involvement in regulating gene
      expression during inflammatory processes and diseases.

PMID- 29657271
TI  - High Percentage of Isomeric Human MicroRNA and Their Analytical Challenges.
AB  - MicroRNA (miR) are short non-coding RNAs known to post-transcriptionally regulate
      gene expression, and have been reported as biomarkers for various diseases. miR
      have also been served as potential drug targets. The identity, functions and
      detection of a specific miR are determined by its RNA sequence, whose composition
      is made up of only 4 canonical ribonucleotides. Hence, among over two thousand
      human miR, their nucleotide compositions are expected to be similar but the
      extent of similarity has not been reported. In this study, the sequences of
      mature human miR were downloaded from miRBase, and collated using different tools
      to determine and compare their nucleotide compositions and sequences. 55% of all
      human miR were found to be structural isomers. The structural isomers of miR
      (SimiR) are defined as having the same size and identical nucleotide composition.
      A number of SimiR were also found to have high sequence similarities. To
      investigate the extent of SimiR in biological samples, three disease models were
      chosen, and disease-associated miR were identified from miR2Disease. Among the
      disease models, as high as 73% of miR were found to be SimiR. This report
      provides the missing information about human miR and highlights the challenges on
      the detection of SimiR.

PMID- 29657272
TI  - Current perspectives in Set7 mediated stem cell differentiation.
AB  - Set7 is a key regulatory enzyme involved in the methylation of lysine residues of
      histone and non-histone proteins. This lysine methyltransferase is induced during
      stem cell differentiation and regulates lineage specific gene transcription and
      cell fate. In this article we discuss recent experimental evidence identifying
      regulatory targets under the control of Set7 as well as emerging evidence of
      regulation in stem cell differentiation. Furthermore, we discuss the function of
      non-coding RNAs regulated by Set7 implicated in cell plasticity.

PMID- 29657273
TI  - Recent Advances in Identification of RNA Modifications.
AB  - RNA modifications are involved in a broad spectrum of biological and
      physiological processes. To reveal the functions of RNA modifications, it is
      important to accurately predict their positions. Although high-throughput
      experimental techniques have been proposed, they are cost-ineffective. As good
      complements of experiments, many computational methods have been proposed to
      predict RNA modification sites in recent years. In this review, we will summarize
      the existing computational approaches directed at predicting RNA modification
      sites. We will also discuss the challenges and future perspectives in developing
      reliable methods for predicting RNA modification sites.

PMID- 29657274
TI  - Computational Approaches to tRNA-Derived Small RNAs.
AB  - tRNA-derived small RNAs (tDRs) are a group of small, non-coding RNAs derived from
      transfer RNAs (tRNAs). They can be classified as tRNA halves and tRNA-derived
      small RNA fragments (tRFs). Accumulating experimental evidence suggests their
      functional roles in cells and in various biological processes. Advances in next
      generation sequencing (NGS) techniques allow a large amount of small RNA deep
      sequencing data to be generated. To investigate tDRs from these data, software to
      identify tDRs and databases to retrieve or manage tDR data have been devised. In
      this review, we summarized the tools and databases for tDR identification and
      collection, with the aim of helping researchers choose the best tools for their
      analysis and inspiring the invention or improvement of tools in the field.

PMID- 29657275
TI  - Evolution of Fungal U3 snoRNAs: Structural Variation and Introns.
AB  - The U3 small nucleolar RNA (snoRNA) is an essential player in the initial steps
      of ribosomal RNA biogenesis which is ubiquitously present in Eukarya. It is
      exceptional among the small nucleolar RNAs in its size, the presence of multiple
      conserved sequence boxes, a highly conserved secondary structure core, its
      biogenesis as an independent gene transcribed by polymerase III, and its
      involvement in pre-rRNA cleavage rather than chemical modification. Fungal U3
      snoRNAs share many features with their sisters from other eukaryotic kingdoms but
      differ from them in particular in their 5' regions, which in fungi has a
      distinctive consensus structure and often harbours introns. Here we report on a
      comprehensive homology search and detailed analysis of the evolution of sequence
      and secondary structure features covering the entire kingdom Fungi.

PMID- 29657277
TI  - Insights into the Function of Long Noncoding RNAs in Sepsis Revealed by Gene Co
      Expression Network Analysis.
AB  - Sepsis is a major cause of death and its incidence and mortality increase
      exponentially with age. Most gene expression studies in sepsis have focused in
      protein-coding genes and the expression patterns, and potential roles of long
      noncoding RNAs (lncRNAs) have not been investigated yet. In this study, we
      performed co-expression network analysis of protein-coding and lncRNAs measured
      in neutrophil granulocytes from adult and elderly septic patients, along with age
      matched healthy controls. We found that the genes displaying highest network
      similarity are predominantly differently expressed in sepsis and are enriched in
      loci encoding proteins with structural or regulatory functions related to protein
      translation and mitochondrial energetic metabolism. A number of lncRNAs are
      strongly connected to genes from these pathways and may take part in regulatory
      loops that are perturbed in sepsis. Among those, the ribosomal pseudogenes RP11
      302F12.1 and RPL13AP7 are differentially expressed and appear to have a
      regulatory role on protein translation in both the elderly and adults, and
      lncRNAs MALAT1, LINC00355, MYCNOS, and AC010970.2 display variable connection
      strength and inverted expression patterns between adult and elderly networks,
      suggesting that they are the best candidates to be further studied to understand
      the mechanisms by which the immune response is impaired by age. In summary, we
      report the expression of lncRNAs that are deregulated in patients with sepsis,
      including subsets that display hub properties in molecular pathways relevant to
      the disease pathogenesis and that may participate in gene expression regulatory
      circuits related to the poorer disease outcome observed in elderly subjects.

PMID- 29657278
TI  - A Brief Review of RNA-Protein Interaction Database Resources.
AB  - RNA-protein interactions play critical roles in various biological processes. By
      collecting and analyzing the RNA-protein interactions and binding sites from
      experiments and predictions, RNA-protein interaction databases have become an
      essential resource for the exploration of the transcriptional and post
      transcriptional regulatory network. Here, we briefly review several widely used
      RNA-protein interaction database resources developed in recent years to provide a
      guide of these databases. The content and major functions in databases are
      presented. The brief description of database helps users to quickly choose the
      database containing information they interested. In short, these RNA-protein
      interaction database resources are continually updated, but the current state
      shows the efforts to identify and analyze the large amount of RNA-protein
      interactions.

PMID- 29657279
TI  - oncoNcRNA: A Web Portal for Exploring the Non-Coding RNAs with Oncogenic
      Potentials in Human Cancers.
AB  - Non-coding RNAs (ncRNAs) have been shown to contribute to tumorigenesis and
      progression. However, the functions of the majority of ncRNAs remain unclear.
      Through integrating published large-scale somatic copy number alterations (SCNAs)
      data from various human cancer types, we have developed oncoNcRNA, a user
      friendly web portal to explore ncRNAs with oncogenic potential in human cancers.
      The portal characterizes the SCNAs of over 58,000 long non-coding RNAs (lncRNAs),
      34,000 piwi-interacting RNAs (piRNAs), 2700 microRNAs (miRNAs), 600 transfer RNAs
      (tRNAs) and 400 small nucleolar RNAs (snoRNAs) in 64 human cancer types. It
      enables researchers to rapidly and intuitively analyze the oncogenic potential of
      ncRNAs of interest. Indeed, we have discovered a large number of ncRNAs which are
      frequently amplified or deleted within and across tumor types. Moreover, we built
      a web-based tool, Correlations, to explore the relationships between gene
      expression and copy number from ~10,000 tumor samples in 36 cancer types
      identified by The Cancer Genome Atlas (TCGA). oncoNcRNA is a valuable tool for
      investigating the function and clinical relevance of ncRNAs in human cancers.
      oncoNcRNA is freely available at http://rna.sysu.edu.cn/onconcrna/.

PMID- 29657280
TI  - CirComPara: A Multi-Method Comparative Bioinformatics Pipeline to Detect and
      Study circRNAs from RNA-seq Data.
AB  - Circular RNAs (circRNAs) are generated by backsplicing of immature RNA forming
      covalently closed loops of intron/exon RNA molecules. Pervasiveness, evolutionary
      conservation, massive and regulated expression, and posttranscriptional
      regulatory roles of circRNAs in eukaryotes have been appreciated and described
      only recently. Moreover, being easily detectable disease markers, circRNAs
      undoubtedly represent a molecular class with high bearing on molecular
      pathobiology. CircRNAs can be detected from RNAseq data using appropriate
      computational methods to identify the sequence reads spanning backsplice
      junctions that do not colinearly map to the reference genome. To this end,
      several programs were developed and critical assessment of various strategies and
      tools suggested the combination of at least two methods as good practice to
      guarantee robust circRNA detection. Here,we present CirComPara
      (http://github.com/egaffo/CirComPara), an automated bioinformatics pipeline, to
      detect, quantify and annotate circRNAs from RNAseq data using in parallel four
      different methods for backsplice identification. CirComPara also provides
      quantification of linear RNAs and gene expression, ultimately comparing and
      correlating circRNA and gene/transcript expression level. We applied our method
      to RNAseqdata of monocyte and macrophage samples in relation to
      haploinsufficiency of the RNAbinding splicing factor Quaking (QKI). The
      biological relevance of the results, in terms of number, types and variations of
      circRNAs expressed, illustrates CirComPara potential to enlarge the knowledge of
      the transcriptome, adding details on the circRNAome, and facilitating further
      computational and experimental studies.

PMID- 29657281
TI  - RNA Biomarkers: Frontier of Precision Medicine for Cancer.
AB  - As an essential part of central dogma, RNA delivers genetic and regulatory
      information and reflects cellular states. Based on high-throughput sequencing
      technologies, cumulating data show that various RNA molecules are able to serve
      as biomarkers for the diagnosis and prognosis of various diseases, for instance,
      cancer. In particular, detectable in various bio-fluids, such as serum, saliva
      and urine, extracellular RNAs (exRNAs) are emerging as non-invasive biomarkers
      for earlier cancer diagnosis, tumor progression monitor, and prediction of
      therapy response. In this review, we summarize the latest studies on various
      types of RNA biomarkers, especially extracellular RNAs, in cancer diagnosis and
      prognosis, and illustrate several well-known RNA biomarkers of clinical utility.
      In addition, we describe and discuss general procedures and issues in
      investigating exRNA biomarkers, and perspectives on utility of exRNAs in
      precision medicine.

PMID- 29657284
TI  - MicroRNA Expression in Bovine Cumulus Cells in Relation to Oocyte Quality.
AB  - Cumulus cells play an essential role during oocyte maturation and the acquisition
      of fertilizability and developmental competence. Micro(mi)RNAs can post
      transcriptionally regulate mRNA expression, and we hypothesized that miRNA
      profiles in cumulus cells could serve as an indicator of oocyte quality. Cumulus
      cell biopsies from cumulus-oocyte-complexes that either yielded a blastocyst or
      failed to cleave after exposure to sperm cells were analyzed for miRNA
      expression. On average, 332 miRNA species with more than 10 reads and 240 miRNA
      species with more than 50 reads were identified in cumulus cells; this included
      nine previously undescribed microRNAs. The most highly expressed miRNAs in
      cumulus cells were miR-21, members of the let-7 family and miR-155. However, no
      repeatable differences in miRNA expression between the cumulus cells from oocytes
      that became blastocysts versus those from non-cleaved oocytes were identified.
      Further examination of individual cumulus cell samples showed a wide variability
      in miRNA expression level. We therefore conclude that miRNA expression in cumulus
      cells cannot be used as an oocyte quality marker.

PMID- 29657282
TI  - Vesiculated Long Non-Coding RNAs: Offshore Packages Deciphering Trans-Regulation
      between Cells, Cancer Progression and Resistance to Therapies.
AB  - Extracellular vesicles (EVs) are nanosized vesicles secreted from virtually all
      cell types and are thought to transport proteins, lipids and nucleic acids
      including non-coding RNAs (ncRNAs) between cells. Since, ncRNAs are central to
      transcriptional regulation during developmental processes; eukaryotes might have
      evolved novel means of post-transcriptional regulation by trans-locating ncRNAs
      between cells. EV-mediated transportation of regulatory elements provides a novel
      source of trans-regulation between cells. In the last decade, studies were mainly
      focused on microRNAs; however, functions of long ncRNA (lncRNA) have been much
      less studied. Here, we review the regulatory roles of EV-linked ncRNAs, placing a
      particular focus on lncRNAs, how they can foster dictated patterns of trans
      regulation in recipient cells. This refers to envisaging novel mechanisms of
      epigenetic regulation, cellular reprogramming and genomic instability elicited in
      recipient cells, ultimately permitting the generation of cancer initiating cell
      phenotypes, senescence and resistance to chemotherapies. Conversely, such trans
      regulation may introduce RNA interference in recipient cancer cells causing the
      suppression of oncogenes and anti-apoptotic proteins; thus favoring tumor
      inhibition. Collectively, understanding these mechanisms could be of great value
      to EV-based RNA therapeutics achieved through gene manipulation within cancer
      cells, whereas the ncRNA content of EVs from cancer patients could serve as non
      invasive source of diagnostic biomarkers and prognostic indicators in response to
      therapies.

PMID- 29657283
TI  - PlantRNA_Sniffer: A SVM-Based Workflow to Predict Long Intergenic Non-Coding RNAs
      in Plants.
AB  - Non-coding RNAs (ncRNAs) constitute an important set of transcripts produced in
      the cells of organisms. Among them, there is a large amount of a particular class
      of long ncRNAs that are difficult to predict, the so-called long intergenic
      ncRNAs (lincRNAs), which might play essential roles in gene regulation and other
      cellular processes. Despite the importance of these lincRNAs, there is still a
      lack of biological knowledge and, currently, the few computational methods
      considered are so specific that they cannot be successfully applied to other
      species different from those that they have been originally designed to.
      Prediction of lncRNAs have been performed with machine learning techniques.
      Particularly, for lincRNA prediction, supervised learning methods have been
      explored in recent literature. As far as we know, there are no methods nor
      workflows specially designed to predict lincRNAs in plants. In this context, this
      work proposes a workflow to predict lincRNAs on plants, considering a workflow
      that includes known bioinformatics tools together with machine learning
      techniques, here a support vector machine (SVM). We discuss two case studies that
      allowed to identify novel lincRNAs, in sugarcane (Saccharum spp.) and in maize
      (Zea mays). From the results, we also could identify differentially-expressed
      lincRNAs in sugarcane and maize plants submitted to pathogenic and beneficial
      microorganisms.

PMID- 29657285
TI  - MicroRNA MultiTool: A Software for Identifying Modified and Unmodified Human
      microRNA Using Mass Spectrometry.
AB  - microRNA (miRNA) are short endogenous non-coding RNA that play a crucial role in
      post-transcriptional gene regulation and have been implicated in the initiation
      and progression of 160+ human diseases. Excellent analytical methods have been
      developed for the measurement of miRNA by mass spectrometry. However,
      interpretation of mass spectrometric data has been an incapacitating bottleneck
      in miRNA identification. This study details the development of MicroRNA
      MultiTool, a software for the identification of miRNA from mass spectrometric
      data. The software includes capabilities such as miRNA search and mass
      calculator, modified miRNA mass calculator, and miRNA fragment search. MicroRNA
      MultiTool bridges the gap between experimental data and identification of miRNA
      by providing a rapid means of mass spectrometric data interpretation.

PMID- 29657286
TI  - Long Non-Coding RNAs Regulating Immunity in Insects.
AB  - Recent advances in modern technology have led to the understanding that not all
      genetic information is coded into protein and that the genomes of each and every
      organism including insects produce non-coding RNAs that can control different
      biological processes. Among RNAs identified in the last decade, long non-coding
      RNAs (lncRNAs) represent a repertoire of a hidden layer of internal signals that
      can regulate gene expression in physiological, pathological, and immunological
      processes. Evidence shows the importance of lncRNAs in the regulation of host
      pathogen interactions. In this review, an attempt has been made to view the role
      of lncRNAs regulating immune responses in insects.

PMID- 29657287
TI  - Identification of RNA Polymerase III-Transcribed SINEs at Single-Locus Resolution
      from RNA Sequencing Data.
AB  - Short Interspersed Element (SINE) retrotransposons are one of the most abundant
      DNA repeat elements in the human genome. They have been found to impact the
      expression of protein-coding genes, but the possible roles in cell physiology of
      their noncoding RNAs, generated by RNA polymerase (Pol) III, are just starting to
      be elucidated. For this reason, Short Interspersed Element (SINE) expression
      profiling is becoming mandatory to obtain a comprehensive picture of their
      regulatory roles. However, their repeated nature and frequent location within Pol
      II-transcribed genes represent a serious obstacle to the identification and
      quantification of genuine, Pol III-derived SINE transcripts at single-locus
      resolution on a genomic scale. Among the recent Next Generation Sequencing
      technologies, only RNA sequencing (RNA-Seq) holds the potential to solve these
      issues, even though both technical and biological matters need to be taken into
      account. A bioinformatic pipeline has been recently set up that, by exploiting
      RNA-seq features and knowledge of SINE transcription mechanisms, allows for easy
      identification and profiling of transcriptionally active genomic loci which are a
      source of genuine Pol III SINE transcripts.

PMID- 29657288
TI  - Computational Characterization of ncRNA Fragments in Various Tissues of the
      Brassica rapa Plant.
AB  - Recently, a novel type of non-coding RNA (ncRNA), known as ncRNA fragments or
      ncRFs, has been characterised in various organisms, including plants. The
      biogenesis mechanism, function and abundance of ncRFs stemming from various
      ncRNAs are poorly understood, especially in plants. In this work, we have
      computationally analysed the composition of ncRNAs and the fragments that derive
      from them in various tissues of Brassica rapa plants, including leaves, meristem
      tissue, pollen, unfertilized and fertilized ova, embryo and endosperm. Detailed
      analysis of transfer RNA (tRNA) fragments (tRFs), ribosomal RNA (rRNA) fragments
      (rRFs), small nucleolar RNA (snoRNA) fragments (snoRFs) and small nuclear RNA
      (snRNA) fragments (snRFs) showed a predominance of tRFs, with the 26 nucleotides
      (nt) fraction being the largest. Mapping ncRF reads to full-length mature ncRNAs
      showed a strong bias for one or both termini. tRFs mapped predominantly to the 5'
      end, whereas snRFs mapped to the 3' end, suggesting that there may be specific
      biogenesis and retention mechanisms. In the case of tRFs, specific isoacceptors
      were enriched, including tRNAGly(UCC) and tRFAsp(GUC). The analysis showed that
      the processing of 26-nt tRF5' occurred by cleavage at the last unpaired
      nucleotide of the loop between the D arm and the anticodon arm. Further support
      for the functionality of ncRFs comes from the analysis of binding between ncRFs
      and their potential targets. A higher average percentage of binding at the first
      half of fragments was observed, with the highest percentage being at 2-6 nt. To
      summarise, our analysis showed that ncRFs in B. rapa are abundantly produced in a
      tissue-specific manner, with bias toward a terminus, the bias toward the size of
      generated fragments and the bias toward the targeting of specific biological
      processes.

PMID- 29657289
TI  - Present Scenario of Long Non-Coding RNAs in Plants.
AB  - Small non-coding RNAs have been extensively studied in plants over the last
      decade. In contrast, genome-wide identification of plant long non-coding RNAs
      (lncRNAs) has recently gained momentum. LncRNAs are now being recognized as
      important players in gene regulation, and their potent regulatory roles are being
      studied comprehensively in eukaryotes. LncRNAs were first reported in humans in
      1992. Since then, research in animals, particularly in humans, has rapidly
      progressed, and a vast amount of data has been generated, collected, and
      organized using computational approaches. Additionally, numerous studies have
      been conducted to understand the roles of these long RNA species in several
      diseases. However, the status of lncRNA investigation in plants lags behind that
      in animals (especially humans). Efforts are being made in this direction using
      computational tools and high-throughput sequencing technologies, such as the
      lncRNA microarray technique, RNA-sequencing (RNA-seq), RNA capture sequencing,
      (RNA CaptureSeq), etc. Given the current scenario, significant amounts of data
      have been produced regarding plant lncRNAs, and this amount is likely to increase
      in the subsequent years. In this review we have documented brief information
      about lncRNAs and their status of research in plants, along with the plant
      specific resources/databases for information retrieval on lncRNAs.

PMID- 29657290
TI  - Deciphering microRNAs and Their Associated Hairpin Precursors in a Non-Model
      Plant, Abelmoschus esculentus.
AB  - MicroRNAs (miRNAs) are crucial regulatory RNAs, originated from hairpin
      precursors. For the past decade, researchers have been focusing extensively on
      miRNA profiles in various plants. However, there have been few studies on the
      global profiling of precursor miRNAs (pre-miRNAs), even in model plants. Here,
      for the first time in a non-model plant-Abelmoschus esculentus with negligible
      genome information-we are reporting the global profiling to characterize the
      miRNAs and their associated pre-miRNAs by applying a next generation sequencing
      approach. Preliminarily, we performed small RNA (sRNA) sequencing with five
      biological replicates of leaf samples to attain 207,285,863 reads; data analysis
      using miRPlant revealed 128 known and 845 novel miRNA candidates. With the
      objective of seizing their associated hairpin precursors, we accomplished pre
      miRNA sequencing to attain 83,269,844 reads. The paired end reads are merged and
      adaptor trimmed, and the resulting 40-241 nt (nucleotide) sequences were picked
      out for analysis by using perl scripts from the miRGrep tool and an in-house
      built shell script for Minimum Fold Energy Index (MFEI) calculation. Applying the
      stringent criteria of the Dicer cleavage pattern and the perfect stem loop
      structure, precursors for 57 known miRNAs of 15 families and 18 novel miRNAs were
      revealed. Quantitative Real Time (qRT) PCR was performed to determine the
      expression of selected miRNAs.

PMID- 29657292
TI  - The Non-Coding RNA Journal Club: Highlights on Recent Papers-5.
AB  - We are delighted to share with you our fifth Journal Club and highlight some of
      the most interesting papers published recently.[...].

PMID- 29657291
TI  - Detecting Disease Specific Pathway Substructures through an Integrated Systems
      Biology Approach.
AB  - In the era of network medicine, pathway analysis methods play a central role in
      the prediction of phenotype from high throughput experiments. In this paper, we
      present a network-based systems biology approach capable of extracting disease
      perturbed subpathways within pathway networks in connection with expression data
      taken from The Cancer Genome Atlas (TCGA). Our system extends pathways with
      missing regulatory elements, such as microRNAs, and their interactions with
      genes. The framework enables the extraction, visualization, and analysis of
      statistically significant disease-specific subpathways through an easy to use web
      interface. Our analysis shows that the methodology is able to fill the gap in
      current techniques, allowing a more comprehensive analysis of the phenomena
      underlying disease states.

PMID- 29657294
TI  - Rare Splice Variants in Long Non-Coding RNAs.
AB  - Long non-coding RNAs (lncRNAs) form a substantial component of the transcriptome
      and are involved in a wide variety of regulatory mechanisms. Compared to protein
      coding genes, they are often expressed at low levels and are restricted to a
      narrow range of cell types or developmental stages. As a consequence, the
      diversity of their isoforms is still far from being recorded and catalogued in
      its entirety, and the debate is ongoing about what fraction of non-coding RNAs
      truly conveys biological function rather than being "junk". Here, using a
      collection of more than 100 transcriptomes from related B cell lymphoma, we show
      that lncRNA loci produce a very defined set of splice variants. While some of
      them are so rare that they become recognizable only in the superposition of
      dozens or hundreds of transcriptome datasets and not infrequently include introns
      or exons that have not been included in available genome annotation data, there
      is still a very limited number of processing products for any given locus. The
      combined depth of our sequencing data is large enough to effectively exhaust the
      isoform diversity: the overwhelming majority of splice junctions that are
      observed at all are represented by multiple junction-spanning reads. We conclude
      that the human transcriptome produces virtually no background of RNAs that are
      processed at effectively random positions, but is-under normal circumstances
      confined to a well defined set of splice variants.

PMID- 29657293
TI  - miR-146 and miR-155: Two Key Modulators of Immune Response and Tumor Development.
AB  - MicroRNAs (miRNAs or miRs) are a class of evolutionarily-conserved small,
      regulatory non-coding RNAs, 19-3 nucleotides in length, that negatively regulate
      protein coding gene transcripts' expression. miR-146 (146a and 146b) and miR-155
      are among the first and most studied miRs for their multiple roles in the control
      of the innate and adaptive immune processes and for their deregulation and
      oncogenic role in some tumors. In the present review, we have focused on the
      recent acquisitions about the key role played by miR-146a, miR-146b and miR-155
      in the control of the immune system and in myeloid tumorigenesis. Growing
      experimental evidence indicates an opposite role of miR-146a with respect to miR
      155 in the fine regulation of many steps of the immune response, acting at the
      level of the various cell types involved in innate and adaptive immune
      mechanisms. The demonstration that miR-155 overexpression plays a key pathogenic
      role in some lymphomas and acute myeloid leukemias has led to the development of
      an antagomir-based approach as a new promising therapeutic strategy.

PMID- 29657295
TI  - Expression Profiling Identifies the Noncoding Processed Transcript of HNRNPU with
      Proliferative Properties in Pancreatic Ductal Adenocarcinoma.
AB  - A gene array was used to profile the expression of 22,875 long non-coding RNAs
      (lncRNAs) and a large number of protein coding genes in 47 specimens of
      pancreatic ductal adenocarcinoma (PDAC), adjacent benign pancreas and the
      pancreas from patients without pancreatic disease. Of the lncRNAs profiled, the
      expression of 126 were significantly increased and 260 were decreased in the
      tumors (p < 0.05, 2-fold). The expression of one lncRNA in particular,
      heterogeneous nuclear ribonucleoprotein U (HNRNPU) processed transcript (also
      known as ncRNA00201) was among the most significantly deregulated (increased four
      fold) in the tumors compared to normal/adjacent benign tissues. Increased
      expression of HNRNPU processed transcript was associated with poor prognosis for
      patients with PDAC. The expression of HNRNPU processed transcript was increased
      in PDAC cell lines compared to noncancerous pancreatic cell lines. LNATM gapmer
      mediated inhibition of HNRNPU processed transcript reduced cell proliferation in
      Patu-T and PL45 pancreatic cancer cell lines. Reduced invasion and migration was
      reported upon HNRNPU processed transcript knockdown in Patu-T cells. Small
      interfering RNA (siRNA) knockdown of the HNRNPU protein coding gene correlated
      with a 55% reduction in the HNRNPU processed transcript expression and a
      corresponding reduction in proliferation of Patu-T and PL45 cells. However,
      gapmer inhibition of HNRNPU processed transcript did not affect HNRNPU mRNA
      levels. The lncRNA HNRNPU processed transcript expression is increased in both
      PDAC tissues and cell lines; knockdown of this lncRNA further reduces
      proliferation and invasion/migration of pancreatic carcinoma cells.

PMID- 29657297
TI  - Long Non-Coding RNA TUG1 Expression Is Associated with Different Subtypes in
      Human Breast Cancer.
AB  - Taurine upregulated 1 gene (TUG1) is a long non-coding RNA associated with
      several types of cancer. Recently, differential expression of TUG1 was found in
      cancerous breast tissues and associated with breast cancer malignancy features.
      Although this is evidence of a potential role in breast cancer, TUG1 expression
      could not be associated with different subtypes, possibly due to the small number
      of samples analyzed. Breast cancer is a heterogeneous disease and, based on
      molecular signatures, may be classified into different subtypes with prognostic
      implications. In the present study, we include analysis of TUG1 expression in 796
      invasive breast carcinoma and 105 normal samples of RNA sequencing (RNA-seq)
      datasets from The Cancer Genome Atlas (TCGA) and describe that TUG1 expression is
      increased in HER2-enriched and basal-like subtypes compared to luminal A.
      Additionally, TUG1 expression is associated with survival in HER2-enriched
      patients. These results reinforce the importance of TUG1 in breast cancer and
      outline its potential impact on specific subtypes.

PMID- 29657296
TI  - Roles of Non-Coding RNA in Sugarcane-Microbe Interaction.
AB  - Studies have highlighted the importance of non-coding RNA regulation in plant
      microbe interaction. However, the roles of sugarcane microRNAs (miRNAs) in the
      regulation of disease responses have not been investigated. Firstly, we screened
      the sRNA transcriptome of sugarcane infected with Acidovorax avenae. Conserved
      and novel miRNAs were identified. Additionally, small interfering RNAs (siRNAs)
      were aligned to differentially expressed sequences from the sugarcane
      transcriptome. Interestingly, many siRNAs aligned to a transcript encoding a
      copper-transporter gene whose expression was induced in the presence of A.
      avenae, while the siRNAs were repressed in the presence of A. avenae. Moreover, a
      long intergenic non-coding RNA was identified as a potential target or decoy of
      miR408. To extend the bioinformatics analysis, we carried out independent
      inoculations and the expression patterns of six miRNAs were validated by
      quantitative reverse transcription-PCR (qRT-PCR). Among these miRNAs, miR408-a
      copper-microRNA-was downregulated. The cleavage of a putative miR408 target, a
      laccase, was confirmed by a modified 5'RACE (rapid amplification of cDNA ends)
      assay. MiR408 was also downregulated in samples infected with other pathogens,
      but it was upregulated in the presence of a beneficial diazotrophic bacteria. Our
      results suggest that regulation by miR408 is important in sugarcane sensing
      whether microorganisms are either pathogenic or beneficial, triggering specific
      miRNA-mediated regulatory mechanisms accordingly.

PMID- 29657298
TI  - A Novel Long Non-Coding RNA in the hTERT Promoter Region Regulates hTERT
      Expression.
AB  - A novel antisense transcript was identified in the human telomerase reverse
      transcriptase (hTERT) promoter region, suggesting that the hTERT promoter is
      bidirectional. This transcript, named hTERT antisense promoter-associated
      (hTAPAS) RNA, is a 1.6 kb long non-coding RNA. hTAPAS transcription is initiated
      167 nucleotides upstream of the hTERT transcription start site and is present in
      both the nucleus and the cytoplasm. Surprisingly, we observed that a large
      fraction of the hTERT polyadenylated RNA is localized in the nucleus, suggesting
      this might be an additional means of regulating the cellular abundance of hTERT
      protein. Both hTAPAS and hTERT are expressed in immortalized B-cells and human
      embryonic stem cells but are not detected in normal somatic cells. hTAPAS
      expression inversely correlates with hTERT expression in different types of
      cancer samples. Moreover, hTAPAS expression is not promoted by an hTERT promoter
      mutation (-124 C>T). Antisense-oligonucleotide mediated knockdown of hTAPAS
      results in an increase in hTERT expression. Conversely, ectopic overexpression of
      hTAPAS down regulates hTERT expression, suggesting a negative role in hTERT gene
      regulation. These observations provide insights into hTAPAS as a novel player
      that negatively regulates hTERT expression and may be involved in telomere length
      homeostasis.

PMID- 29657301
TI  - Unravelling the Long Non-Coding RNA Profile of Undifferentiated Large Cell Lung
      Carcinoma.
AB  - Undifferentiated large cell lung carcinoma (LCLC) accounts for 2.9-9% of total
      lung cancers. Recently, RNA-seq based studies have revealed major genomic
      aberrations in LCLC. In this study, we aim to identify long non-coding RNAs
      (LncRNAs) expression pattern specific to LCLC. The RNA-seq profile of LCLC and
      other non-small cell lung carcinoma (NSCLC) was downloaded from Gene Expression
      Omnibus (GEO) and analyzed. Using 10 LCLC samples, we found that 18% of all the
      annotated LncRNAs are expressed in LCLC samples. Among 1794 expressed LncRNAs, 11
      were overexpressed and 14 were downregulated in LCLC compared to normal samples.
      Based on receiver operating characteristic (ROC) analysis, we showed that the top
      five differentially expressed LncRNAs were able to differentiate between LCLC and
      normal samples with high sensitivity and specificity. Guilt by association
      analysis using genes correlating with differentially expressed LncRNAs identified
      several cancer-associated pathways, suggesting the role of these deregulated
      LncRNA in LCLC biology. We also identified the LncRNA differentially expressed in
      LCLC compared to lung squamous carcinoma (LUSC) and Lung-adenocarcinoma (LUAD).
      We found that LCLC sample showed more deregulated LncRNA in LUSC than LUAD.
      Interestingly, LCLC had more downregulated LncRNA compared to LUAD and LUSC. Our
      study provides novel insight into LncRNA deregulation in LCLC. This study also
      finds tools to diagnose LCLC and differentiate LCLC with other Non-Small Cell
      Lung Cancer.

PMID- 29657300
TI  - Besides Pathology: Long Non-Coding RNA in Cell and Tissue Homeostasis.
AB  - A significant proportion of mammalian genomes corresponds to genes that
      transcribe long non-coding RNAs (lncRNAs). Throughout the last decade, the number
      of studies concerning the roles played by lncRNAs in different biological
      processes has increased considerably. This intense interest in lncRNAs has
      produced a major shift in our understanding of gene and genome regulation and
      structure. It became apparent that lncRNAs regulate gene expression through
      several mechanisms. These RNAs function as transcriptional or post
      transcriptional regulators through binding to histone-modifying complexes, to
      DNA, to transcription factors and other DNA binding proteins, to RNA polymerase
      II, to mRNA, or through the modulation of microRNA or enzyme function. Often, the
      lncRNA transcription itself rather than the lncRNA product appears to be
      regulatory. In this review, we highlight studies identifying lncRNAs in the
      homeostasis of various cell and tissue types or demonstrating their effects in
      the expression of protein-coding or other non-coding RNA genes.

PMID- 29657302
TI  - miRNAtools: Advanced Training Using the miRNA Web of Knowledge.
AB  - Micro-RNAs (miRNAs) are small non-coding RNAs that act as negative regulators of
      the genomic output. Their intrinsic importance within cell biology and human
      disease is well known. Their mechanism of action based on the base pairing
      binding to their cognate targets have helped the development not only of many
      computer applications for the prediction of miRNA target recognition but also of
      specific applications for functional assessment and analysis. Learning about
      miRNA function requires practical training in the use of specific computer and
      web-based applications that are complementary to wet-lab studies. In order to
      guide the learning process about miRNAs, we have created miRNAtools
      (http://mirnatools.eu), a web repository of miRNA tools and tutorials. This
      article compiles tools with which miRNAs and their regulatory action can be
      analyzed and that function to collect and organize information dispersed on the
      web. The miRNAtools website contains a collection of tutorials that can be used
      by students and tutors engaged in advanced training courses. The tutorials engage
      in analyses of the functions of selected miRNAs, starting with their nomenclature
      and genomic localization and finishing with their involvement in specific
      cellular functions.

PMID- 29657303
TI  - Sponge Long Non-Coding RNAs Are Expressed in Specific Cell Types and Conserved
      Networks.
AB  - Although developmental regulation by long non-coding RNAs (lncRNAs) appears to be
      a widespread feature amongst animals, the origin and level of evolutionary
      conservation of this mode of regulation remain unclear. We have previously
      demonstrated that the sponge Amphimedon queenslandica-a morphologically-simple
      animal-developmentally expresses an array of lncRNAs in manner akin to more
      complex bilaterians (insects + vertebrates). Here, we first show that Amphimedon
      lncRNAs are expressed in specific cell types in larvae, juveniles and adults.
      Thus, as in bilaterians, sponge developmental regulation involves the dynamic,
      cell type- and context-specific regulation of specific lncRNAs. Second, by
      comparing gene co-expression networks between Amphimedon queenslandica and Sycon
      ciliatum-a distantly-related calcisponge-we identify several putative co
      expression modules that appear to be shared in sponges; these network-embedded
      sponge lncRNAs have no discernable sequence similarity. Together, these results
      suggest sponge lncRNAs are developmentally regulated and operate in conserved
      gene regulatory networks, as appears to be the case in more complex bilaterians.

PMID- 29657304
TI  - The Role of Long Non-Coding RNAs in Osteosarcoma.
AB  - Long non-coding RNAs (lncRNAs) constitute non-protein coding transcripts with a
      size > than 200 nucleotides. They are involved in many cellular processes, such
      as chromatin remodelling, transcription, and gene expression. They play a role in
      the development, progression, and invasion of many human cancers, including
      osteosarcoma. This rare tumor entity predominantly arises in children and young
      adults. Treatment consists of polychemotherapy and surgical resection, increasing
      survival rates up to 60%. In the present review, the role of lncRNAs with
      prognostic, predictive, therapeutic, and diagnostic significance in osteosarcoma
      is discussed. Moreover, their potential application in clinical practice is
      highlighted.

PMID- 29657305
TI  - Strengths and Weaknesses of the Current Strategies to Map and Characterize R
      Loops.
AB  - R-loops are evolutionarily conserved three-stranded structures that result from
      the formation of stable DNA:RNA hybrids in the genome. R-loops have attracted
      increasing interest in recent years as potent regulators of gene expression and
      genome stability. In particular, their strong association with severe replication
      stress makes them potential oncogenic structures. Despite their importance, the
      rules that govern their formation and their dynamics are still controversial and
      an in-depth description of their direct impact on chromatin organization and DNA
      transactions is still lacking. To better understand the diversity of R-loop
      functions, reliable, accurate, and quantitative mapping techniques, as well as
      functional assays are required. Here, I review the different approaches that are
      currently used to do so and to highlight their individual strengths and
      weaknesses. In particular, I review the advantages and disadvantages of using the
      S9.6 antibody to map R-loops in vivo in an attempt to propose guidelines for best
      practices.

PMID- 29657306
TI  - Hypoxia-Induced MicroRNA-210 Targets Neurodegenerative Pathways.
AB  - Hypoxia-regulated microRNA-210 (miR-210) is a highly conserved microRNA, known to
      regulate various processes under hypoxic conditions. Previously we found that miR
      210 is also involved in honeybee learning and memory, raising the questions of
      how neural activity may induce hypoxia-regulated genes and how miR-210 may
      regulate plasticity in more complex mammalian systems. Using a pull-down
      approach, we identified 620 unique target genes of miR-210 in humans, among which
      there was a significant enrichment of age-related neurodegenerative pathways,
      including Huntington's, Alzheimer's, and Parkinson's diseases. We have also
      validated that miR-210 directly regulates various identified target genes of
      interest involved with neuronal plasticity, neurodegenerative diseases, and miR
      210-associated cancers. This data suggests a potentially novel mechanism for how
      metabolic changes may couple plasticity to neuronal activity through hypoxia
      regulated genes such as miR-210.

PMID- 29657308
TI  - Characteristics of gut microbiota in adult patients with type 1 and type 2
      diabetes based on next-generation sequencing of the 16S rRNA gene fragment.
AB  - Introduction Scientific data indicate a possible influence of gut microbiota on
      the development of type 1 and type 2 diabetes mellitus (T1DM and T2DM,
      respectively). Sequence analysis of 16S ribosomal RNA identified several hundred
      bacterial species of the intestinal ecosystem, most of which cannot be cultured.
      Objectives We aimed to evaluate gut microbiota composition in adult patients with
      T1DM and T2DM and establish a link between microbiological test results and
      patients' clinical data. Patients and methods We examined DNA isolated from fecal
      samples in 3 groups: healthy volunteers (n = 23), patients with T1DM (n = 22),
      and patients with T2DM (n = 23). Next-generation sequencing was performed on the
      MiSeq platform. Results At the phylum level, the Firmicutes bacteria prevailed
      (>77%) in all groups. At the taxonomic levels L2 (phylum) and L6 (genus),
      significant differences were demonstrated in bacterial profiles, particularly in
      the T2DM group. A negative correlation was observed between several genera of
      bacteria and the percentage of glycated hemoglobin A1c in the T2DM group, while a
      positive correlation was revealed between bacteria belonging to the genus
      Bifidobacterium and high-density lipoprotein cholesterol levels in both T1DM and
      T2DM groups. Conclusions Our results provide grounds for conducting research in
      the field of gut microbiota in order to develop individualized therapy for
      patients with diabetes based on modifying the microbiota composition, as a new
      method for controlling glycemia. Next-generation sequencing allows a rapid
      identification of the DNA of all bacteria present in the sample and their
      taxonomic classification.

PMID- 29657309
TI  - Advanced hypertrophic obstructive cardiomyopathy diagnosed in early pregnancy:
      successful prevention of sudden cardiac death.

PMID- 29657310
TI  - Cardiac amyloidosis: myocardial biopsy as a tool in chemotherapy implementation
      and sudden cardiac death prevention.

PMID- 29657307
TI  - Non-Coding RNA as Novel Players in the Pathophysiology of Schizophrenia.
AB  - Schizophrenia is associated with diverse changes in the brain's transcriptome and
      proteome. Underlying these changes is the complex dysregulation of gene
      expression and protein production that varies both spatially across brain regions
      and temporally with the progression of the illness. The growing body of
      literature showing changes in non-coding RNA in individuals with schizophrenia
      offers new insights into the mechanisms causing this dysregulation. A large
      number of studies have reported that the expression of microRNA (miRNA) is
      altered in the brains of individuals with schizophrenia. This evidence is
      complemented by findings that single nucleotide polymorphisms (SNPs) in miRNA
      host gene sequences can confer an increased risk of developing the disorder.
      Additionally, recent evidence suggests the expression of other non-coding RNAs,
      such as small nucleolar RNA and long non-coding RNA, may also be affected in
      schizophrenia. Understanding how these changes in non-coding RNAs contribute to
      the development and progression of schizophrenia offers potential avenues for the
      better treatment and diagnosis of the disorder. This review will focus on the
      evidence supporting the involvement of non-coding RNA in schizophrenia and its
      therapeutic potential.

PMID- 29657311
TI  - Successful surgical treatment of pheochromocytoma during pregnancy.

PMID- 29657312
TI  - Left Upper-Quadrant Appendicitis in a Patient with Congenital Intestinal
      Malrotation and Polysplenia.
AB  - BACKGROUND Appendicitis is the most common cause of abdominal pain requiring
      emergent surgical intervention. Although typically presenting as right lower
      quadrant pain, in rare cases it may present as left upper-quadrant pain secondary
      to abnormal position due to intestinal malrotation. Since atypical presentations
      may result in diagnostic and management delay, increasing morbidity and
      mortality, accurate and prompt diagnosis is important. Therefore, acute
      appendicitis should be considered in the differential diagnosis of left upper
      quadrant abdominal pain. In this setting, medical imaging plays a key role in
      diagnosis. We report a case of a 13-year-old female with undiagnosed intestinal
      malrotation presenting with left-sided acute appendicitis. CASE REPORT A 13-year
      old Hispanic female presented at the emergency room with anorexia and left upper
      quadrant abdominal pain with involuntary guarding. The laboratory work-up was
      remarkable for elevated white blood cell count and elevated erythrocyte
      sedimentation rate. A nasogastric tube was placed and abdominal x-rays performed
      to rule-out bowel obstruction, showing distended bowel loops throughout all
      abdominal quadrants, with sigmoid and proximal rectal gas, raising concern for
      ileus rather than an obstructive pattern. Lack of symptomatic improvement
      prompted an IV contrast-enhanced abdominopelvic CT, revealing intestinal
      malrotation and with an inflamed left upper-quadrant appendix. Surgical
      management proceeded with a laparoscopic Ladd's procedure. CONCLUSIONS Acute
      appendicitis may present with atypical symptoms due to unusual appendix
      locations, such as in malrotation. Most cases are asymptomatic until development
      of acute complications, requiring imaging for diagnosis. Clinicians and
      radiologists should have a high index of suspicion and knowledge of its clinical
      presentations to achieve early diagnosis and intervention.

PMID- 29657314
TI  - Author Correction: Selection of reference genes for microRNA analysis associated
      to early stress response to handling and confinement in Salmo salar.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 29657313
TI  - Curcumin Attenuates Inflammation in a Severe Acute Pancreatitis Animal Model by
      Regulating TRAF1/ASK1 Signaling.
AB  - BACKGROUND Inflammation plays an important role in initiation and development of
      severe acute pancreatitis (SAP). Curcumin exerts potent anti-inflammatory effects
      in many diseases, including acute pancreatitis. However, the specific molecular
      mechanisms are not clear. MATERIAL AND METHODS Intra-biliopancreatic duct
      injection of taurocholate was used to establish an animal model of SAP. Curcumin
      was administrated to animals as pre-treatments. Concentrations of cytokines in
      serum and ascites were measured by enzyme-linked immunosorbent assay (ELISA). A
      colorimetric method was used to determine the amylase activity. Western blotting
      was used to examine the expression levels and phosphorylation levels of proteins.
      Immunoprecipitation was used to assess the molecular association between
      apoptosis signal- regulating kinase 1 (ASK1) and thioredoxin (Trx). RESULTS Pre
      treatment with curcumin reduced the concentrations of interleukin (IL6) and tumor
      necrosis factor (TNFalpha) in serum and ascites, as well as the ascites volume
      and amylase activity in SAP rats. Pre-treatment with curcumin reduced the
      expression level of TNF receptor-associated factor 1 (TRAF1), IL6, and TNFa in
      pancreas in SAP rats. Moreover, the phosphorylation levels of mitogen-activated
      protein kinase (MAPK) kinase 4 (MKK4), MKK7, and c-Jun NH(2)-terminal protein
      kinase (JNK) were reduced by curcumin pre-treatment. The molecular association
      between ASK1 and Trx was recovered by curcumin pre-treatment. As a result, the
      nuclear translocation of nuclear factor kappa B (NF-kappaB) was suppressed in
      pancreases from SAP rats. CONCLUSIONS Activation of the TRAF1/ASK1/JNK/NF-kappaB
      signaling pathway is involved in the inflammation of SAP. Curcumin exerts anti
      inflammatory effects by suppressing this proinflammatory pathway.

PMID- 29657315
TI  - Author Correction: Next generation sequencing reveals changes of the gammadelta T
      cell receptor repertoires in patients with pulmonary tuberculosis.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 29657316
TI  - Legless baby amphibians dine on mother's skin.

PMID- 29657317
TI  - Gentle 'slow slip' earthquakes belie hidden danger.

PMID- 29657319
TI  - Speedy nanoengine zooms along DNA tracks.

PMID- 29657318
TI  - Jays play nicely with the right hormone.

PMID- 29657320
TI  - Why fit fathers sire smarter offspring.

PMID- 29657321
TI  - Deadly tumours are often born of childhood mutations.

PMID- 29657322
TI  - Laser-beam 'tweezers' guide two atoms to collide.

PMID- 29657323
TI  - A stomach virus's mysterious path into the gut is uncovered.

PMID- 29657325
TI  - Author Correction: Nod2 and Nod2-regulated microbiota protect BALB/c mice from
      diet-induced obesity and metabolic dysfunction.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 29657324
TI  - Recent advances in cancer metabolism: a technological perspective.
AB  - Cancer cells are highly dependent on metabolic pathways to sustain both their
      proliferation and adaption to harsh microenvironments. Thus, understanding the
      metabolic reprogramming that occurs in tumors can provide critical insights for
      the development of therapies targeting metabolism. In this review, we will
      discuss recent advancements in metabolomics and other multidisciplinary
      techniques that have led to the discovery of novel metabolic pathways and
      mechanisms in diverse cancer types.

PMID- 29657326
TI  - Exploring vitamin D metabolism and function in cancer.
AB  - Vitamin D, traditionally known as an essential nutrient, is a precursor of a
      potent steroid hormone that regulates a broad spectrum of physiological
      processes. In addition to its classical roles in bone metabolism,
      epidemiological, preclinical, and cellular research during the last decades, it
      revealed that vitamin D may play a key role in the prevention and treatment of
      many extra-skeletal diseases such as cancer. Vitamin D, as a prohormone,
      undergoes two-step metabolism in liver and kidney to produce a biologically
      active metabolite, calcitriol, which binds to the vitamin D receptor (VDR) for
      the regulation of expression of diverse genes. In addition, recent studies have
      revealed that vitamin D can also be metabolized and activated through a CYP11A1
      driven non-canonical metabolic pathway. Numerous anticancer properties of vitamin
      D have been proposed, with diverse effects on cancer development and progression.
      However, accumulating data suggest that the metabolism and functions of vitamin D
      are dysregulated in many types of cancer, conferring resistance to the
      antitumorigenic effects of vitamin D and thereby contributing to the development
      and progression of cancer. Thus, understanding dysregulated vitamin D metabolism
      and function in cancer will be critical for the development of promising new
      strategies for successful vitamin D-based cancer therapy.

PMID- 29657327
TI  - A guide to 13C metabolic flux analysis for the cancer biologist.
AB  - Cancer metabolism is significantly altered from normal cellular metabolism
      allowing cancer cells to adapt to changing microenvironments and maintain high
      rates of proliferation. In the past decade, stable-isotope tracing and network
      analysis have become powerful tools for uncovering metabolic pathways that are
      differentially activated in cancer cells. In particular, 13C metabolic flux
      analysis (13C-MFA) has emerged as the primary technique for quantifying
      intracellular fluxes in cancer cells. In this review, we provide a practical
      guide for investigators interested in getting started with 13C-MFA. We describe
      best practices in 13C-MFA, highlight potential pitfalls and alternative
      approaches, and conclude with new developments that can further enhance our
      understanding of cancer metabolism.

PMID- 29657329
TI  - Expanding the concepts of cancer metabolism.

PMID- 29657330
TI  - Does pregnancy coloration reduce female conspecific aggression in the presence of
      maternal kin?
AB  - Colour signals arise in a variety of sexual contexts, including advertising
      reproductive status. Despite potentially attracting negative attention from
      unrelated competitors, bright pregnancy coloration may communicate gestation to
      kin and potential fathers, thereby garnering aid during agonistic encounters and
      reducing the overall amount of aggression received by pregnant females. To
      establish whether this 'pregnancy sign' influences rates of aggression in the
      presence versus absence of maternal kin, we conducted behavioural observations of
      wild olive baboons, Papio anubis, in Gombe National Park, Tanzania, in groups
      composed of maternal kin and nonkin, and of captive baboons at the Southwest
      National Primate Research Center (SNPRC, San Antonio, TX, U.S.A.), in group
      enclosures that were unlikely to include close kin. At SNPRC, we also
      experimentally obscured the coloration of the pregnancy sign, and we performed
      playback experiments to measure male responses to the distress calls of pregnant
      females. Free-ranging female baboons experienced significantly less aggression
      from nonkin females after the onset of the pregnancy sign compared to the pre
      pregnancy sign. In contrast, captive pregnant females whose pregnancy coloration
      was obscured with paint experienced significantly lower aggression rates from
      female conspecifics compared to pre-painting. Male aggression towards females did
      not differ in the presence versus absence of the pregnancy sign in either the
      wild or the captive population, although captive fathers paid significantly more
      attention to distress calls of pregnant cage-mates than they did to those of
      cycling cage-mates, suggesting a willingness to aid mothers that were carrying
      their unborn offspring.

PMID- 29657331
TI  - The Role of Compensatory Beliefs in Rationalizing Environmentally Detrimental
      Behaviors.
AB  - Compensatory green beliefs (CGBs) reflect the idea that a pro-environmental
      behavior (e.g., recycling) can off-set the negative effects of an environmentally
      detrimental behavior (e.g., driving). It is thought that CGBs might help explain
      why people act in ways that appear to contradict their pro-environmental
      intentions, and inconsistently engage in pro-environmental behaviors. The present
      study sought to investigate the nature and use of CGBs. A series of interviews
      suggested that participants endorsed CGBs to (a) reduce feelings of guilt with
      respect to (the assumed or actual) negative environmental impact of their actions
      and (b) defend their green credentials in social situations. Participants also
      justified detrimental behaviors on the basis of higher loyalties (e.g., family's
      needs), or the perceived difficulty of performing more pro-environmental actions.
      In addition to shedding light on how, when, and why people might hold and use
      CGBs, the research also provides new insight into how CGBs should be assessed.

PMID- 29657328
TI  - Non-canonical functions of enzymes facilitate cross-talk between cell metabolic
      and regulatory pathways.
AB  - The metabolic rewiring that occurs during cell transformation is a hallmark of
      cancer. It is diverse in different cancers as it reflects different combinations
      of oncogenic drivers, tumor suppressors, and the microenvironment. Metabolic
      rewiring is essential to cancer as it enables uncontrolled proliferation and
      adaptation to the fluctuating availability of nutrients and oxygen caused by poor
      access to the vasculature due to tumor growth and a foreign microenvironment
      encountered during metastasis. Increasing evidence now indicates that the
      metabolic state in cancer cells also plays a causal role in tumor growth and
      metastasis, for example through the action of oncometabolites, which modulate
      cell signaling and epigenetic pathways to promote malignancy. In addition to
      altering the metabolic state in cancer cells, some multifunctional enzymes
      possess non-metabolic functions that also contribute to cell transformation. Some
      multifunctional enzymes that are highly expressed in cancer, such as pyruvate
      kinase M2 (PKM2), have non-canonical functions that are co-opted by oncogenic
      signaling to drive proliferation and inhibit apoptosis. Other multifunctional
      enzymes that are frequently downregulated in cancer, such as fructose
      bisphosphatase 1 (FBP1), are tumor suppressors, directly opposing mitogenic
      signaling via their non-canonical functions. In some cases, the enzymatic and non
      canonical roles of these enzymes are functionally linked, making the modulation
      of non-metabolic cellular processes dependent on the metabolic state of the cell.

PMID- 29657332
TI  - LITHOBATES PIPIENS (Northern Leopard Frog). MALFORMATION.

PMID- 29657333
TI  - Optimized ARROW-Based MMI Waveguides for High Fidelity Excitation Patterns for
      Optofluidic Multiplexing.
AB  - Multimode interference (MMI) waveguides can be used for multiplexing and de
      multiplexing optical signals. High fidelity, wavelength dependent multi-spot
      patterns from MMI waveguides are useful for sensitive and simultaneous
      identification of multiple targets in multiplexed fluorescence optofluidic
      biosensors. Through experiments and simulation, this paper explores design
      parameters for an MMI rib anti-resonant reflecting optical waveguide (ARROW) in
      order to produce high fidelity spot patterns at the liquid core biomarker
      excitation region. Width and etch depth of the single excitation rib waveguide
      used to excite the MMI waveguide are especially critical because they determine
      the size of the input optical mode which is imaged at the MMI waveguide's output.
      To increase optical throughput into the MMI waveguide when light is coupled in
      from an optical fiber, tapers in the waveguide width can be used for better mode
      matching.

PMID- 29657334
TI  - Awareness, Analysis, and Action: Curricular Alignment for Student Success in
      General Chemistry.
AB  - This article examines the ways that a shared faculty experience across five
      partner institutions led to a deep awareness of the curriculum and pedagogy of
      general chemistry coursework, and ultimately, to a collaborative action plan for
      student success. The team identified key differences and similarities in course
      content and instructional experiences. The comparative analysis yielded many more
      similarities than differences, and therefore, the team shifted its focus from
      "gap analysis" to an exploration of common curricular challenges. To address
      these challenges, the team developed content for targeted instructional resources
      that promoted the success of all STEM students across institutions. This article
      contextualizes the interinstitutional collaboration and closely examines the
      interactive components (awareness, analysis, and action), critical tools, and
      productive attitudes that undergirded the curricular alignment process of the
      STEM Transfer Student Success Initiative (t-STEM).

PMID- 29657335
TI  - Parental Education and Family Dissolution: A Cross-National and Cohort
      Comparison.
AB  - This is the first study to systematically analyze whether the association between
      parental education and family dissolution varies cross-nationally and over time.
      The authors use meta-analytic tools to study cross-national variation between 17
      countries with data from the Generations and Gender Study and Harmonized
      Histories. The association shows considerable cross-national variation, but is
      positive in most countries. The association between parental education and family
      dissolution has become less positive or even negative in six countries. The
      findings show that the association between parental education and family
      dissolution is generally positive or nil, even if the association between own
      education and family dissolution is in many countries increasingly negative. The
      authors find suggestive evidence that the association is related to the crude
      divorce rate, but not to the generosity of the welfare state in these countries.
      The implications of these findings for understanding the stratification in family
      dissolution are discussed.

PMID- 29657336
TI  - The Role of Rough Topography in Mediating Impacts of Bottom Drag in Eddying Ocean
      Circulation Models.
AB  - Motivated by the substantial sensitivity of eddies in two-layer quasi-geostrophic
      (QG) turbulence models to the strength of bottom drag, this study explores the
      sensitivity of eddies in more realistic ocean general circulation model (OGCM)
      simulations to bottom drag strength. The OGCM results are interpreted using
      previous results from horizontally homogeneous, two-layer, flat-bottom, f-plane,
      doubly periodic QG turbulence simulations and new results from two-layer beta
      plane QG turbulence simulations run in a basin geometry with both flat and rough
      bottoms. Baroclinicity in all of the simulations varies greatly with drag
      strength, with weak drag corresponding to more barotropic flow and strong drag
      corresponding to more baroclinic flow. The sensitivity of the baroclinicity in
      the QG basin simulations to bottom drag is considerably reduced, however, when
      rough topography is used in lieu of a flat bottom. Rough topography reduces the
      sensitivity of the eddy kinetic energy amplitude and horizontal length scales in
      the QG basin simulations to bottom drag to an even greater degree. The OGCM
      simulation behavior is qualitatively similar to that in the QG rough bottom basin
      simulations in that baroclinicity is more sensitive to bottom drag strength than
      are eddy amplitudes or horizontal length scales. Rough topography therefore
      appears to mediate the sensitivity of eddies in models to the strength of bottom
      drag. The sensitivity of eddies to parameterized topographic internal lee wave
      drag, which has recently been introduced into some OGCMs, is also briefly
      discussed. Wave drag acts like a strong bottom drag in that it increases the
      baroclinicity of the flow, without strongly affecting eddy horizontal length
      scales.

PMID- 29657337
TI  - Pressure-anisotropy-induced nonlinearities in the kinetic magnetorotational
      instability.
AB  - In collisionless and weakly collisional plasmas, such as hot accretion flows onto
      compact objects, the magnetorotational instability (MRI) can differ significantly
      from the standard (collisional) MRI. In particular, pressure anisotropy with
      respect to the local magnetic-field direction can both change the linear MRI
      dispersion relation and cause nonlinear modifications to the mode structure and
      growth rate, even when the field and flow perturbations are very small. This work
      studies these pressure-anisotropy-induced nonlinearities in the weakly nonlinear,
      high-ion-beta regime, before the MRI saturates into strong turbulence. Our goal
      is to better understand how the saturation of the MRI in a low-collisionality
      plasma might differ from that in the collisional regime. We focus on two key
      effects: (i) the direct impact of self-induced pressure-anisotropy nonlinearities
      on the evolution of an MRI mode, and (ii) the influence of pressure anisotropy on
      the 'parasitic instabilities' that are suspected to cause the mode to break up
      into turbulence. Our main conclusions are: (i) The mirror instability regulates
      the pressure anisotropy in such a way that the linear MRI in a collisionless
      plasma is an approximate nonlinear solution once the mode amplitude becomes
      larger than the background field (just as in magnetohyrodynamics). This implies
      that differences between the collisionless and collisional MRI become unimportant
      at large amplitudes. (ii) The break up of large-amplitude MRI modes into
      turbulence via parasitic instabilities is similar in collisionless and
      collisional plasmas. Together, these conclusions suggest that the route to
      magnetorotational turbulence in a collisionless plasma may well be similar to
      that in a collisional plasma, as suggested by recent kinetic simulations. As a
      supplement to these findings, we offer guidance for the design of future kinetic
      simulations of magnetorotational turbulence.

PMID- 29657338
TI  - Size-Dependent Submerging of Nanoparticles in Polymer Melts: Effect of Line
      Tension.
AB  - Adhesion of nanoparticles to polymer films plays a key role in various polymer
      technologies. Here we report experiments that reveal how silica nanoparticles
      adhere to a viscoelastic PMMA film above the glass transition temperature. The
      polymer was swollen with CO2, closely matching the conditions of nanoparticle
      nucleated polymer foaming. It is found that the degree by which the particles
      sink into the viscoelastic substrate is strongly size dependent and can even lead
      to complete engulfment for particles of diameter below 12 nm. These findings are
      explained quantitatively by a thermodynamic analysis, combining elasticity,
      capillary adhesion, and line tension. We argue that line tension, here proposed
      for the first time in elastic media, is responsible for the nanoparticle
      engulfment.

PMID- 29657339
TI  - On the value of carbon-ion therapy.

PMID- 29657340
TI  - Critical Consciousness: A Critique and Critical Analysis of the Literature.
AB  - The education system has been heralded as a tool of liberation and simultaneously
      critiqued as a tool of social control to maintain the oppressive status quo.
      Critical consciousness (CC), developed by the Brazilian educator, Paulo Freire,
      advanced an educational pedagogy to liberate the masses from systemic inequity
      maintained and perpetuated by process, practices and outcomes of interdependent
      systems and institutions. If people are not aware of inequity and do not act to
      constantly resist oppressive norms and ways of being, then the result is residual
      inequity in perpetuity. If inequity is likened to a disease or poison, then CC
      has been deemed the antidote to inequity and the prescription needed to break the
      cycle. As such, CC is a construct that has important scholarly, practice and
      policy implications. Scholars, noting the relevance and application of CC to
      current social problems, have advanced CC theory and practice. However, these
      innovative advancements have left fissures in the CC theoretical base in need of
      resolution and consensus to advance a collective and organized body of CC theory.
      This paper explores the divergent CC scholarship within CC theory and practice
      articles, provides an in-depth review of the inconsistencies, and suggests ideas
      to resolve the discrepancies from the literature to support the need for a new,
      CC-based construct, transformative potential. Without such a review, moving
      toward conceptual clarity, the lack of a coherent CC knowledgebase will impede
      the reflection and action needed to transform systems and institutions that
      maintain and perpetuate systemic inequity that have dehumanizing consequences. If
      implemented within urban education, theoretical models, grounded in CC theory,
      could help achieve a system of education that is just, equitable and liberating.

PMID- 29657341
TI  - Coordination Polymers based on the Neutral Ditopic Ligand (C6H4PO(OCH3)2)2
      Involving some f-Block Elements.
AB  - An improved synthesis using microwave heating affords (C6H4PO(OCH3)2)2 in
      excellent isolated yield (95 %). The ligand properties of this
      bisphosphonateester were explored towards hard metal centers M2+ (M = Ca, UO2)
      and M3+ (M = La, Ce, Sm, Eu) resulting in coordination polymers, for which the
      reduction of ionic size of the central metal atom resulted in lower-dimensional
      structural motifs as opposed to higher dimensional networks obtained for the
      larger ions. All coordination polymers were characterized by single-crystal X-ray
      diffraction, IR spectroscopy, and combustion analysis. The ligand was furthermore
      characterized with multinuclear NMR spectroscopy.

PMID- 29657342
TI  - L-band microwave remote sensing and land data assimilation improve the
      representation of pre-storm soil moisture conditions for hydrologic forecasting.
AB  - Recent advances in remote sensing and land data assimilation purport to improve
      the quality of antecedent soil moisture information available for operational
      hydrologic forecasting. We objectively validate this claim by calculating the
      strength of the relationship between storm-scale runoff ratio (i.e., total stream
      flow divided by total rainfall accumulation in depth units) and pre-storm surface
      soil moisture estimates from a range of surface soil moisture data products.
      Results demonstrate that both satellite-based, L-band microwave radiometry and
      the application of land data assimilation techniques have significantly improved
      the utility of surface soil moisture data sets for forecasting stream flow
      response to future rainfall events.

PMID- 29657343
TI  - Joint Sentinel-1 and SMAP data assimilation to improve soil moisture estimates.
AB  - SMAP (Soil Moisture Active and Passive) radiometer observations at ~40 km
      resolution are routinely assimilated into the NASA Catchment Land Surface Model
      to generate the 9-km SMAP Level-4 Soil Moisture product. This study demonstrates
      that adding high-resolution radar observations from Sentinel-1 to the SMAP
      assimilation can increase the spatio-temporal accuracy of soil moisture
      estimates. Radar observations were assimilated either separately from or
      simultaneously with radiometer observations. Assimilation impact was assessed by
      comparing 3-hourly, 9-km surface and root-zone soil moisture simulations with in
      situ measurements from 9-km SMAP core validation sites and sparse networks, from
      May 2015 to December 2016. The Sentinel-1 assimilation consistently improved
      surface soil moisture, whereas root-zone impacts were mostly neutral. Relatively
      larger improvements were obtained from SMAP assimilation. The joint assimilation
      of SMAP and Sentinel-1 observations performed best, demonstrating the
      complementary value of radar and radiometer observations.

PMID- 29657344
TI  - Increased atmospheric ammonia over the world's major agricultural areas detected
      from space.
AB  - This study provides evidence of substantial increases in atmospheric ammonia
      (NH3) concentrations (14-year) over several of the worlds major agricultural
      regions, using recently available retrievals from the Atmospheric Infrared
      Sounder (AIRS) aboard NASA's Aqua satellite. The main sources of atmospheric NH3
      are farming and animal husbandry involving reactive nitrogen ultimately derived
      from fertilizer use; rates of emission are also sensitive to climate change.
      Significant increasing trends are seen over the US (2.61% yr-1), the European
      Union (EU) (1.83% yr-1), and China (2.27% yr-1). Over the EU, the trend results
      from decreased scavenging by acid aerosols. Over the US, the increase results
      from a combination of decreased chemical loss and increased soil temperatures.
      Over China, decreased chemical loss, increasing temperatures, and increased
      fertilizer use all play a role. Over South Asia, increased NH3 emissions are
      masked by increased SO2 and NOx emissions, leading to increased aerosol loading
      and adverse health effects.

PMID- 29657345
TI  - Communalism Moderates the Association Between Racial Centrality and Emergency
      Department Use for Sickle Cell Disease Pain.
AB  - Sickle cell disease (SCD) is a genetic blood disorder that predominantly affects
      people of African descent. However, there is limited information on how social
      and cultural contexts affect SCD-related health care use. We explored whether
      communalism moderated the relation between racial centrality and emergency
      department use for SCD pain in a sample of 62 adults who were seen at a
      comprehensive clinic. Bivariate analyses showed a significant correlation between
      racial centrality and emergency department use (r = -.30, p = .02). Pain-adjusted
      regression analyses indicated a moderating effect of communalism (b = .77, p <
      .01) such that an inverse association between racial centrality and emergency
      department use was observed only at mean and low levels of communalism.
      Additional studies are needed to replicate these findings with larger samples.
      There is also a need for further studies that elucidate the role of culturally
      centered coping strategies on health care use in this patient group.

PMID- 29657347
TI  - Affect Intensity Moderates the Association of Emotional Clarity with Emotion
      Regulation and Depressive Symptoms in Unselected and Treatment-Seeking Samples.
AB  - Depression is associated with subjective difficulties identifying one's emotions,
      known as low emotional clarity, but the mediators and moderators of this
      relationship are not well understood. We hypothesized that the role of emotional
      clarity in emotion regulation and, in turn, depression depends on individual
      differences in negative affect intensity. In Study 1, conducted in an unselected
      sample (N=119), low emotional clarity more strongly predicted depression symptoms
      among individuals higher in affect intensity. In Study 2, conducted in a
      clinically diagnosed, treatment-seeking sample (N=245), we examined whether
      affect intensity moderated an indirect path of clarity through emotion regulation
      strategy use that has emerged in previous work. When affect intensity was very
      low, emotional clarity did not predict reappraisal, and when affect intensity was
      very high, emotional clarity did not predict non-acceptance or experiential
      avoidance. By contrast, rumination mediated associations of emotional clarity
      with depressive symptoms regardless of affect intensity. Findings support a
      process model of low emotional clarity in depression that integrates (1) emotion
      regulatory mediators and (2) moderation by negative affect intensity. Trait
      differences in affect intensity may determine whether and how emotional clarity
      and regulation processes factor into mood psychopathology.

PMID- 29657346
TI  - Weathering of pyrogenic organic matter induces fungal oxidative enzyme response
      in single culture inoculation experiments.
AB  - The addition of pyrogenic organic matter (PyOM), the aromatic carbon-rich product
      of the incomplete combustion of plant biomass or fossil fuels, to soil can
      influence the rate of microbial metabolism of native soil carbon. The interaction
      of soil heterotrophs with PyOM may be governed by the surficial chemical and
      physical properties of PyOM that evolve with environmental exposure. We present
      results of a 36-day laboratory incubation investigating the interaction of a
      common white-rot fungus, Trametes versicolor, with three forms of 13C-enriched
      (2.08 atom% 13C) PyOM derived from Pinus ponderosa (450  degrees C): one freshly
      produced, and two artificially weathered (254 nm, UV light-water treatment and
      water-leaching alone). Analysis (FTIR, XPS) of the UV-weathered PyOM showed
      increased aliphatic C-H content and oxidation of aromatic carbon relative to both
      the original and water-leached PyOM. The addition of both weathered forms of PyOM
      stimulated (positively primed) fungal respiration of the growth media, while the
      unaltered PyOM mildly inhibited (negatively primed) respiration. Artificial
      weathering resulted in higher oxidative (laccase and peroxidase) enzyme activity
      than unaltered PyOM, possibly the result of a diminished capacity to bind
      reactive substrates and extracellular enzymes after weathering. However, and
      contrary to expectations, simple water-leached weathering resulted in a
      relatively higher enzyme activity and respiration than that of UV-weathering. The
      13C content of respired CO2 indicated negligible fungal oxidation of PyOM for all
      treatments, demonstrating the overall low microbial reactivity of this high
      temperature PyOM. The increased enzymatic and positive priming response of T.
      versicolor to weathered PyOM highlights the importance of weathering-induced
      chemistry in controlling PyOM-microbe-soil carbon interactions.

PMID- 29657348
TI  - Rawls's Wide Reflective Equilibrium as a Method for Engaged Interdisciplinary
      Collaboration: Potentials and Limitations for the Context of Technological Risks.
AB  - The introduction of new technologies in society is sometimes met with public
      resistance. Supported by public policy calls for "upstream engagement" and
      "responsible innovation," recent years have seen a notable rise in attempts to
      attune research and innovation processes to societal needs, so that stakeholders'
      concerns are taken into account in the design phase of technology. Both within
      the social sciences and in the ethics of technology, we see many
      interdisciplinary collaborations being initiated that aim to address tensions
      between various normative expectations about science and engineering and the
      actual outcomes. However, despite pleas to integrate social science research into
      the ethics of technology, effective normative models for assessing technologies
      are still scarce. Rawls's wide reflective equilibrium (WRE) is often mentioned as
      a promising approach to integrate insights from the social sciences in the
      normative analysis of concrete cases, but an in-depth discussion of how this
      would work in practice is still lacking. In this article, we explore to what
      extent the WRE method can be used in the context of technology development. Using
      cases in engineering and technology development, we discuss three issues that are
      currently neglected in the applied ethics literature on WRE. The first issue
      concerns the operationalization of abstract background theories to moral
      principles. The second issue concerns the inclusiveness of the method and the
      demand for openness. The third issue is how to establish whether or not an
      equilibrium has been reached. These issues should be taken into account when
      applying the methods to real-world cases involving technological risks. Applying
      the WRE method in the context of engaged interdisciplinary collaboration requires
      sensitivity for issues of power and representativeness to properly deal with the
      dynamics between the technical and normative researchers involved as well as
      society at large.

PMID- 29657350
TI  - Combined Radar-Radiometer Surface Soil Moisture and Roughness Estimation.
AB  - A robust physics-based combined radar-radiometer, or Active-Passive, surface soil
      moisture and roughness estimation methodology is presented. Soil moisture and
      roughness retrieval is performed via optimization, i.e., minimization, of a joint
      objective function which constrains similar resolution radar and radiometer
      observations simultaneously. A data-driven and noise-dependent regularization
      term has also been developed to automatically regularize and balance
      corresponding radar and radiometer contributions to achieve optimal soil moisture
      retrievals. It is shown that in order to compensate for measurement and
      observation noise, as well as forward model inaccuracies, in combined radar
      radiometer estimation surface roughness can be considered a free parameter.
      Extensive Monte-Carlo numerical simulations and assessment using field data have
      been performed to both evaluate the algorithm's performance and to demonstrate
      soil moisture estimation. Unbiased root mean squared errors (RMSE) range from
      0.18 to 0.03 cm3/cm3 for two different land cover types of corn and soybean. In
      summary, in the context of soil moisture retrieval, the importance of consistent
      forward emission and scattering development is discussed and presented.

PMID- 29657349
TI  - The MODIS cloud optical and microphysical products: Collection 6 updates and
      examples from Terra and Aqua.
AB  - The MODIS Level-2 cloud product (Earth Science Data Set names MOD06 and MYD06 for
      Terra and Aqua MODIS, respectively) provides pixel-level retrievals of cloud-top
      properties (day and night pressure, temperature, and height) and cloud optical
      properties (optical thickness, effective particle radius, and water path for both
      liquid water and ice cloud thermodynamic phases-daytime only). Collection 6 (C6)
      reprocessing of the product was completed in May 2014 and March 2015 for MODIS
      Aqua and Terra, respectively. Here we provide an overview of major C6 optical
      property algorithm changes relative to the previous Collection 5 (C5) product.
      Notable C6 optical and microphysical algorithm changes include: (i) new ice cloud
      optical property models and a more extensive cloud radiative transfer code lookup
      table (LUT) approach, (ii) improvement in the skill of the shortwave-derived
      cloud thermodynamic phase, (iii) separate cloud effective radius retrieval
      datasets for each spectral combination used in previous collections, (iv)
      separate retrievals for partly cloudy pixels and those associated with cloud
      edges, (v) failure metrics that provide diagnostic information for pixels having
      observations that fall outside the LUT solution space, and (vi) enhanced pixel
      level retrieval uncertainty calculations. The C6 algorithm changes collectively
      can result in significant changes relative to C5, though the magnitude depends on
      the dataset and the pixel's retrieval location in the cloud parameter space.
      Example Level-2 granule and Level-3 gridded dataset differences between the two
      collections are shown. While the emphasis is on the suite of cloud optical
      property datasets, other MODIS cloud datasets are discussed when relevant.

PMID- 29657351
TI  - Habitat heterogeneity induces rapid changes in the feeding behaviour of
      generalist arthropod predators.
AB  - The "habitat heterogeneity hypothesis" predicts positive effects of structural
      complexity on species coexistence. Increasing habitat heterogeneity can change
      the diversity (number of species, abundances) and the functional roles of
      communities. The latter, however, is not well understood as species and
      individuals may respond very differently and dynamically to a changing
      environment.Here, we experimentally test how habitat heterogeneity affects
      generalist arthropod predators, including epigaeic spiders, carabid and
      staphylinid beetles, under natural conditions by assessing their diversity and
      directly measuring their trophic interactions (which provide a proxy for their
      functional roles). The experiment was conducted in spring barley fields in
      Southern Sweden where habitat heterogeneity was manipulated by increasing within
      field plant diversity.Increased habitat heterogeneity triggered rapid changes in
      the feeding behaviour of generalist predators characterized by lower trophic
      specialization at both network (H2', degree of interaction specialization in the
      entire network) and species level (d', degree of interaction specialization at
      the species level). We presume that this is because spatial separation resulted
      in relaxed competition and allowed an increased overlap in resources used among
      predator species. Predators collected from heterogenous habitats also showed
      greater individual-level dietary variability which might be ascribed to relaxed
      intraspecific competition.Our results provide conclusive evidence that habitat
      heterogeneity can induce rapid behavioural responses independent of changes in
      diversity, potentially promoting the stability of ecosystem functions. A plain
      language summary is available for this article.

PMID- 29657352
TI  - Experience of sleep disruption in primary Sjogren's syndrome: A focus group
      study.
AB  - Introduction: Primary Sjogren's syndrome is the third most common systemic
      autoimmune rheumatic disease, following rheumatoid arthritis and systemic lupus
      erythematosus, and results in dryness, fatigue, discomfort and sleep
      disturbances. Sleep is relatively unexplored in primary Sjogren's syndrome. We
      investigated the experiences of sleep disturbances from the viewpoint of primary
      Sjogren's syndrome patients and their partners and explored the acceptability of
      cognitive behavioural therapy for insomnia. Method: We used focus groups to
      collect qualitative data from 10 patients with primary Sjogren's syndrome and
      three partners of patients. The data were recorded, transcribed verbatim and
      analysed using thematic analysis. Results: Five themes emerged from the data: (a)
      Experience of sleep disturbances; (b) variation and inconsistency in sleep
      disturbances; (c) the domino effect of primary Sjogren's syndrome symptoms; (d)
      strategies to manage sleep; (e) acceptability of evidence-based techniques. Sleep
      disturbances were problematic for all patients, but specific disturbances varied
      between participants. These included prolonged sleep onset time and frequent
      night awakenings and were aggravated by pain and discomfort. Patients deployed a
      range of strategies to try and self-manage. Cognitive behavioural therapy for
      insomnia was seen as an acceptable intervention, as long as a rationale for its
      use is given and it is tailored for primary Sjogren's syndrome. Conclusion:
      Primary Sjogren's syndrome patients described a range of sleep disturbances.
      Applying tailored, evidence-based sleep therapy interventions may improve sleep,
      severity of other primary Sjogren's syndrome symptoms and functional ability.

PMID- 29657353
TI  - Categorical Inequality: Schools As Sorting Machines.
AB  - Despite their egalitarian ethos, schools are social sorting machines, creating
      categories that serve as the foundation of later life inequalities. In this
      review, we apply the theory of categorical inequality to education, focusing
      particularly on contemporary American schools. We discuss the range of categories
      that schools create, adopt, and reinforce, as well as the mechanisms through
      which these categories contribute to production of inequalities within schools
      and beyond. We argue that this categorical inequality frame helps to resolve a
      fundamental tension in the sociology of education and inequality, shedding light
      on how schools can-at once-be egalitarian institutions and agents of inequality.
      By applying the notion of categorical inequality to schools, we provide a set of
      conceptual tools that can help researchers understand, measure, and evaluate the
      ways in which schools structure social inequality.

PMID- 29657354
TI  - A Fourier-Transform Infrared Study of Biochar Aging in Soils.
AB  - We used diffuse reflectance Fourier-transform infrared (DR-FTIR) spectroscopy, X
      ray diffraction (XRD), and chemical and isotopic analyses to characterize the
      light fraction of four contrasting soils (control and biocharamended soils) to
      determine changes in biochar properties after aging. Two Eucalyptus saligna Sm.
      wood biochars, produced at 450 degrees C (B450) and 550 degrees C (B550), were
      incubated separately in each of the four soils for up to 12 mo at 20, 40, and 60
      degrees C. Total C and isotopic (delta13C) methods were used to quantify the
      amounts of biochar C and native C mineralized during incubation. The DR-FTIR
      spectra of the light fraction showed distinct absorption bands representing
      native soil organic C, biochar C, and mineral constituents present in the soils;
      the mineral bands were consistent with XRD data of the clay fraction of the four
      soils. Analysis of the DR-FTIR spectra in the nu(C-H) bands showed that the ratio
      of the aromatic nu(C-H) bands systematically increased relative to the aliphatic
      nu(C-H) bands with increasing mineralization of biochar C in the B550 amended
      soils, and this relationship was unique for each soil type. In contrast, this
      relationship was not observed for the B450 amended soils that contained a
      relatively smaller proportion of aromatic C.

PMID- 29657355
TI  - First-principles modeling of electromagnetic scattering by discrete and
      discretely heterogeneous random media.
AB  - A discrete random medium is an object in the form of a finite volume of a vacuum
      or a homogeneous material medium filled with quasi-randomly and quasi-uniformly
      distributed discrete macroscopic impurities called small particles. Such objects
      are ubiquitous in natural and artificial environments. They are often
      characterized by analyzing theoretically the results of laboratory, in situ, or
      remote-sensing measurements of the scattering of light and other electromagnetic
      radiation. Electromagnetic scattering and absorption by particles can also affect
      the energy budget of a discrete random medium and hence various ambient physical
      and chemical processes. In either case electromagnetic scattering must be modeled
      in terms of appropriate optical observables, i.e., quadratic or bilinear forms in
      the field that quantify the reading of a relevant optical instrument or the
      electromagnetic energy budget. It is generally believed that time-harmonic
      Maxwell's equations can accurately describe elastic electromagnetic scattering by
      macroscopic particulate media that change in time much more slowly than the
      incident electromagnetic field. However, direct solutions of these equations for
      discrete random media had been impracticable until quite recently. This has led
      to a widespread use of various phenomenological approaches in situations when
      their very applicability can be questioned. Recently, however, a new branch of
      physical optics has emerged wherein electromagnetic scattering by discrete and
      discretely heterogeneous random media is modeled directly by using analytical or
      numerically exact computer solutions of the Maxwell equations. Therefore, the
      main objective of this Report is to formulate the general theoretical framework
      of electromagnetic scattering by discrete random media rooted in the Maxwell
      Lorentz electromagnetics and discuss its immediate analytical and numerical
      consequences. Starting from the microscopic Maxwell-Lorentz equations, we trace
      the development of the first-principles formalism enabling accurate calculations
      of monochromatic and quasi-monochromatic scattering by static and randomly
      varying multiparticle groups. We illustrate how this general framework can be
      coupled with state-of-the-art computer solvers of the Maxwell equations and
      applied to direct modeling of electromagnetic scattering by representative random
      multi-particle groups with arbitrary packing densities. This first-principles
      modeling yields general physical insights unavailable with phenomenological
      approaches. We discuss how the first-order-scattering approximation, the
      radiative transfer theory, and the theory of weak localization of electromagnetic
      waves can be derived as immediate corollaries of the Maxwell equations for very
      specific and well-defined kinds of particulate medium. These recent developments
      confirm the mesoscopic origin of the radiative transfer, weak localization, and
      effective-medium regimes and help evaluate the numerical accuracy of widely used
      approximate modeling methodologies.

PMID- 29657356
TI  - Using Modern Methods for Missing Data Analysis with the Social Relations Model: A
      Bridge to Social Network Analysis.

PMID- 29657357
TI  - Independent and Interactive Effects of Neighborhood Disadvantage and Social
      Network Characteristics on Problem Drinking after Treatment.
AB  - Socioecological approaches to public health problems like addiction emphasize the
      importance of person-environment interactions. Neighborhood and social network
      characteristics may influence the likelihood of relapse among individuals in
      recovery, but these factors have been understudied, particularly with respect to
      conceptualizing social network characteristics as moderators of neighborhood
      disadvantage. Drawing from a larger prospective study of individuals recruited
      from outpatient treatment (N=451) and interviewed 1, 3, 5, and 7 years later, the
      aim of this study was to examine the independent and interactive effects of
      neighborhood and social network characteristics on continued problem drinking
      after treatment. Models using generalized estimating equations controlling for
      demographic and other risk factors found the number of heavy drinkers in one's
      network increases risk of relapse, with the effects being significantly stronger
      among those living in disadvantaged neighborhoods than among those in non
      disadvantaged neighborhoods. No independent effects were found for neighborhood
      disadvantage or for the number of network members supporting reduced drinking.
      Future research is needed to examine potential protective factors in
      neighborhoods which may offset socioeconomic disadvantage as well as to
      investigate the functions that network members serve in helping to improve long
      term treatment outcomes.

PMID- 29657358
TI  - Validity and Reliability of Short Physical Activity History: Cardia and the
      Minnesota Heart Health Program.
AB  - Validity and reliability of a short physical activity history were assessed in
      two studies. Validity was studied in 2766 women and 2303 men, participants in
      CARDIA, a biracial study. Ages ranged from 18 to 30 years. The activities
      performed in the past 12 months by >= 50 percent of participants were
      walking/hiking, nonstrenuous sports, shoveling/lifting during leisure,
      running/jogging and home maintenance/gardening. Validity was indirectly assessed
      by studying the relationships of total activity to skinfold thickness, total
      caloric intake, duration on a self-limited maximal exercise test, and high
      density lipoprotein cholesterol. Less than perfect correlation are expected since
      physical activity is not the only factor affecting the validation criteria and
      since physical activity patterns change over time within each person. Comparing
      the highest physical activity quartile to the lowest physical activity quartile,
      mean level of sum of three skinfolds was 10.7 mm less for women (correlation
      coefficient (r) = -0.15, P < 0.001) and 6.9 mm less for men (r = -0.12, P <
      0.001); mean level of caloric intake was 158 kcal morefor women (r = 0.07, P <
      0.001) and 875 kcal morefor men (r = 0.21, P < 0.001); mean level of duration on
      treadmill was 132 seconds more for women (r = 0.36, P < 0.001) and 95 seconds
      more for women (r = 0.25, P < 0.001); and mean level of high density lipoprotein
      cholesterol was 4.8 mg/dL more for women (r = 0.13, P < 0.001) and 3.2 mg/dL more
      for men (r = 0.11, P < 0.001). Reliability was studied in a separate population
      by comparing questionnaire results in an initial telephone administration with
      results obtained two weeks later (N = 129). Similar types and amounts of activity
      were reported in this group as in the group studied for validity. Test-retest
      correlation coefficients for three summary scores ranged from 0.77 to 0.84, and
      were at least 0.57 for each of the 13 activity groupings queried. This
      questionnaire typically takes 5-10 minutes to administer. It yields moderately
      detailed information about type and amount of usual leisure time physical
      activity.

PMID- 29657359
TI  - Direct Numerical Simulation of Fluid Flow and Mass Transfer in Particle Clusters.
AB  - In this paper, an efficient ghost-cell based immersed boundary method is applied
      to perform direct numerical simulation (DNS) of mass transfer problems in
      particle clusters. To be specific, a nine-sphere cuboid cluster and a random
      generated spherical cluster consisting of 100 spheres are studied. In both cases,
      the cluster is composed of active catalysts and inert particles, and the mutual
      influence of particles on their mass transfer performance is studied. To simulate
      active catalysts the Dirichlet boundary condition is imposed at the external
      surface of spheres, while the zero-flux Neumann boundary condition is applied for
      inert particles. Through our studies, clustering is found to have negative
      influence on the mass transfer performance, which can be then improved by
      dilution with inert particles and higher Reynolds numbers. The distribution of
      active/inert particles may lead to large variations of the cluster mass transfer
      performance, and individual particle deep inside the cluster may possess a high
      Sherwood number.

PMID- 29657360
TI  - Interplay between Surface Chemistry, Precursor Reactivity, and Temperature
      Determines Outcome of ZnS Shelling Reactions on CuInS2 Nanocrystals.
AB  - ZnS shelling of I-III-VI2 nanocrystals (NCs) invariably leads to blue-shifts in
      both the absorption and photoluminescence spectra. These observations imply that
      the outcome of ZnS shelling reactions on I-III-VI2 colloidal NCs results from a
      complex interplay between several processes taking place in solution, at the
      surface of, and within the seed NC. However, a fundamental understanding of the
      factors determining the balance between these different processes is still
      lacking. In this work, we address this need by investigating the impact of
      precursor reactivity, reaction temperature, and surface chemistry (due to the
      washing procedure) on the outcome of ZnS shelling reactions on CuInS2 NCs using a
      seeded growth approach. We demonstrate that low reaction temperatures (150 
      degrees C) favor etching, cation exchange, and alloying regardless of the
      precursors used. Heteroepitaxial shell overgrowth becomes the dominant process
      only if reactive S- and Zn-precursors (S-ODE/OLAM and ZnI2) and high reaction
      temperatures (210  degrees C) are used, although a certain degree of
      heterointerfacial alloying still occurs. Remarkably, the presence of residual
      acetate at the surface of CIS seed NCs washed with ethanol is shown to facilitate
      heteroepitaxial shell overgrowth, yielding for the first time CIS/ZnS core/shell
      NCs displaying red-shifted absorption spectra, in agreement with the spectral
      shifts expected for a type-I band alignment. The insights provided by this work
      pave the way toward the design of improved synthesis strategies to CIS/ZnS
      core/shell and alloy NCs with tailored elemental distribution profiles, allowing
      precise tuning of the optoelectronic properties of the resulting materials.

PMID- 29657361
TI  - Cone-beam computed tomography for assessment of dens invaginatus in the Polish
      population.
AB  - Objectives: There are many developmental variations in the permanent dentition.
      Dens invaginatus can be recognized on many dental X-rays of affected patients,
      but not every image allows for assessment of the type of malformation. The aim of
      the present study was to assess the presence of dens invaginatus with
      radiological features using cone-beam computed tomography (CBCT). Methods: CBCT
      images of 33 patients were evaluated. Age, sex, side, lateralization, occurrence
      in a particular group of teeth, type of invagination, differentiation, and the
      consequences of these factors were analyzed. Results: Forty-one teeth with dens
      invaginatus met the inclusion criteria for this evaluation. Females were affected
      more frequently than males (57.6 vs. 42.4%, respectively). The patients' age
      ranged from 7 to 40 years, and the occurrence of dens invaginatus peaked from age
      9 to 13 years. In total, 92.7% of affected teeth were present in the maxilla,
      more often unilaterally (75.8%) than bilaterally (24.2%). The most frequent tooth
      with dens invaginatus was the maxillary lateral incisor (53.7% of affected
      teeth). Almost two-thirds (63.4%) of affected teeth were found on the left side
      and 36.6% were found on the right. The tooth anatomy was distorted within the
      crown and root. Dens invaginatus sometimes affected other surrounding teeth and
      reduced their esthetics. Conclusions: The obtained data indicate that CBCT
      examination is an essential tool in assessing dens invaginatus and can guide
      dental practitioners in treating patients who exhibit characteristic features of
      this disorder. CBCT allows the clinician to distinguish the type of anomaly.

PMID- 29657362
TI  - Seasonality of blood neopterin levels in the Old Order Amish.
AB  - Seasonal changes in non-human animals and seasonal affective disorder (SAD) in
      humans are associated with immune activation in winter relative to summer. We
      intended to measure seasonal variation in neopterin, a marker of cellular
      immunity, and its interactions with gender and seasonality of mood. We studied
      320 Amish from Lancaster, PA, USA (men = 128; 40%) with an average age [Standard
      deviation (SD)] of 56.7 (13.9) years. Blood neopterin level was measured with
      enzyme-linked immunosorbent assay (ELISA). Seasonality was measured with Seasonal
      Pattern Assessment Questionnaire (SPAQ). Statistical analysis included analysis
      of covariance (ANCOVAs) and multivariate linear regression. We also investigated
      interactions of seasonal differences in neopterin with gender, seasonality scores
      and estimation of SAD diagnosis. We found a significantly higher neopterin level
      in winter than in summer (p = 0.006). There were no significant gender or
      seasonality interactions. Our study confirmed the hypothesized higher neopterin
      level in winter. A cross sectional design was our major limitation. If this
      finding will be replicated by longitudinal studies in multiple groups, neopterin
      could be used to monitor immune status across seasons in demographically diverse
      samples, even if heterogeneous in gender distribution, and degree of seasonality
      of mood.

PMID- 29657363
TI  - Positive association between Toxoplasma gondii IgG serointensity and current
      dysphoria/hopelessness scores in the Old Order Amish: a preliminary study.
AB  - Toxoplasma gondii (T. gondii) IgG seropositivity and serointensity have been
      previously associated with suicidal self-directed violence (SSDV). Although
      associations with unipolar depression have also been investigated, the results
      have been inconsistent, possibly as a consequence of high heterogeneity. We have
      now studied this association in a more homogeneous population, [that is (i.e.)
      Old Order Amish (OOA)] with previously reported high T. gondii seroprevalence. In
      306 OOA with a mean age of 46.1 +/- 16.7 years, including 191 (62.4%) women in
      the Amish Wellness Study, we obtained both T. gondii IgG titers (by enzyme-linked
      immunosorbent assay [ELISA]), and depression screening questionnaires (Patient
      Health Questionnaire [PHQ-9] [n = 280] and PHQ-2 [n = 26]). Associations between
      T. gondii IgG and dysphoria/hopelessness and anhedonia scores on depression
      screening questionnaires were analyzed using multivariable linear methods with
      adjustment for age and sex. Serointensity was associated with both current
      dysphoria/hopelessness (p = 0.045) and current combined anhedonia and
      dysphoria/hopelessness (p = 0.043), while associations with simple anhedonia and
      past/lifelong (rather than current) phenotypes were not significant. These
      results indicate the need for larger longitudinal studies to corroborate the
      association between dysphoria/hopelessness and T. gondii IgG-titers. Current
      hopelessness is a known risk factor for SSDV which responds particularly well to
      cognitive behavioral therapy, and may be a focused treatment target for T. gondii
      positive individuals at high-risk for SSDV.

PMID- 29657365
TI  - Organic Photoredox Catalysis as a General Strategy for Anti-Markovnikov Alkene
      Hydrofunctionalization.
AB  - The development of a general catalyst system for the direct anti-Markovnikov
      hydrofunctionalization of alkenes is presented. A unique catalyst system
      comprised of an acridinium photooxidant and a hydrogen atom transfer reagent
      allows for a range of alkene anti-Markovnikov hydrofunctionalization reactions
      including hydroalkoxylation, hydroamination, and hydroacetoxylation.

PMID- 29657364
TI  - Sleep onset insomnia, daytime sleepiness and sleep duration in relationship to
      Toxoplasma gondii IgG seropositivity and serointensity.
AB  - Toxoplasma gondii (T. gondii) infects central nervous tissue and is kept in
      relative dormancy by a healthy immune system. Sleep disturbances have been found
      to precipitate mental illness, suicidal behavior and car accidents, which have
      been previously linked to T. gondii as well. We speculated that if sleep
      disruption, particularly insomnia, would mediate, at least partly, the link
      between T. gondii infection and related behavioral dysregulation, then we would
      be able to identify significant associations between sleep disruption and T.
      gondii. The mechanisms for such an association may involve dopamine (DA)
      production by T. gondii, or collateral effects of immune activation necessary to
      keep T. gondii in check. Sleep questionnaires from 2031 Old Order Amish were
      analyzed in relationship to T. gondii-IgG antibodies measured by enzyme-linked
      immunosorbent assay (ELISA). Toxoplasma gondii seropositivity and serointensity
      were not associated with any of the sleep latency variables or Epworth Sleepiness
      Scale (ESS). A secondary analysis identified, after adjustment for age group, a
      statistical trend toward shorter sleep duration in seropositive men (p = 0.07).
      In conclusion, it is unlikely that sleep disruption mediates links between T.
      gondii and mental illness or behavioral dysregulation. Trending gender
      differences in associations between T. gondii and shorter sleep need further
      investigation.

PMID- 29657366
TI  - Not by bread alone: Lev Vygotsky's Jewish writings.
AB  - On the basis of both published and unpublished manuscripts written from 1914 to
      1917, this article gives an overview of Lev Vygotsky's early ideas. It turns out
      that Vygotsky was very much involved in issues of Jewish culture and politics.
      Rather surprisingly, the young Vygotsky rejected all contemporary ideas to save
      the Jewish people from discrimination and persecution by creating an autonomous
      state in Palestine or elsewhere. Instead, until well into 1917, Vygotsky proposed
      the rather traditional option of strengthening the spiritual roots of the Jews by
      returning to the religious writings. Socialism was rejected, because it merely
      envisioned the compulsory redistribution of material goods and 'man lives not by
      bread alone'. It was only after the October Revolution that Vygotsky switched
      from arguments in favour of the religious faith in the Kingship of God to the
      communist belief in a Radiant Future.

PMID- 29657368
TI  - The Advance Directives and Foregoing of Life Support: Where do we Stand Now?

PMID- 29657367
TI  - Navigational Strategies and Their Neural Correlates.
AB  - Animals depend on navigation to find food, water, mate(s), shelter, etc.
      Different species use diverse strategies that utilise forms of motion- and
      location-related information derived from the environment to navigate to their
      goals and back. We start by describing behavioural studies undertaken to unearth
      different strategies used in navigation. Then we move on to outline what we know
      about the brain area most associated with spatial navigation, namely the
      hippocampal formation. While doing so, we first briefly explain the anatomical
      connections in the area and then proceed to describe the neural correlates that
      are considered to play a role in navigation. We conclude by looking at how the
      strategies might interact and complement each other in certain contexts.

PMID- 29657369
TI  - Factors Affecting the Effective Management of Acute Stroke: A Prospective
      Observational Study.
AB  - Background: Stroke, characterized by sudden loss of cerebral function, is among
      one of the leading cause of death and disability world over. The newer treatment
      modalities have changed the landscape of stroke treatment but are very much time
      bound. Aim: To characterize pre-hospital and in-hospital factors affecting acute
      stroke management thus defining lacunae in stroke management. Subjects and
      Methods: A prospective observational study, conducted at the emergency department
      of a tertiary care center in southern India from August 2015 to July 2016. All
      stroke patients presenting within first 24 hours of onset were included. A pre 
      defined Knowledge-Attitude-Practice (KAP) questionnaire was used. Results: Total
      of 133 patients were eligible out of which 28 were excluded for various reasons.
      Majority were >60 years age and male (61%). About 60% arrived within window.
      Distance from the hospital was one of the major factors for arrival within the
      window period. When compared by KAP questionnaire, bystanders of those arriving
      within window period had better awareness of stroke symptoms. Conclusions:
      Improving awareness of stroke symptoms and increasing availability of EMS is
      likely increase chances of stroke patients receiving appropriate acute
      management.

PMID- 29657370
TI  - Delirium in the Intensive Care Unit: Incidence, Risk Factors, and Impact on
      Outcome.
AB  - Background: The incidence and risk factors for delirium vary among studies.
      Objective: We aimed to determine the incidence, risk factors, and impact on
      outcome of delirium in a medical Intensive Care Unit (ICU) in Tunisia using a
      prospective observational study. Patients: All consecutive patients admitted to
      the ICU between May 2012 and April 2013 were included if they were aged more than
      18 years and had an ICU stay of more than 24 h. Patients who had a cardiac arrest
      or have a history of dementia or psychosis were excluded. Patients eligible for
      the study were evaluated by the medical staff to detect delirium using the CAM
      ICU. Results: A total of 206 patients were included, 167 did not present delirium
      and 39 (19%) were analyzed for delirium. Delirious patients had a significantly
      longer duration of mechanical ventilation (10 days[6-20] vs. 2 days[0-7])
      respectively and length of stay in ICU (21.5 days [10.5-32.5] vs. 8 days [5-13]),
      with no impact on mortality. Delirium was associated with high incidence of
      unintentional removal of catheters (39% vs. 9%; P < 0.0001), endotracheal tubes
      (18% vs. 1%; P < 0.0001), and urinary catheters (28% vs. 2%, P < 0.0001). In
      multivariable risk regression analysis, age (odds ratio [OR] = 4.1, 95%
      confidence interval [CI]: 1.39-12.21; P = 0.01), hypertension (OR = 3.3, 95% CI:
      1.31-8.13; P = 0.011), COPD (OR = 3.5, 95% CI: 1.47-8.59; P = 0.005), steroids
      (OR = 2.8, 95% CI: 1.05-7.28; P = 0.038), and sedation (OR = 5.4, 95% CI: 2.08
      13.9; P < 0.0001) were independent risk factors for delirium. We did not find a
      relationship between delirium and mortality. Conclusion: Delirium is frequent in
      the ICU and is associated with poor outcome. Several risk factors for delirium
      are linked to intensive care environment.

PMID- 29657371
TI  - Comparison of Optic Nerve Sheath Diameter between both eyes: A Bedside
      Ultrasonography Approach.
AB  - Context: Optic nerve sheath diameter (ONSD) has long been accepted as a reliable
      proxy of intracranial pressure especially in critical care and bedside settings.
      The present consensus is to measure ONSD in both eyes and take average value,
      which is cumbersome and a potential cause of discomfort to the patient. Aim: We
      aim to compare the values of ONSD of the right and left eye in a random sample as
      measured by bedside ocular ultrasonography (USG) in Indian adults. Settings and
      Design: This was a prospective study conducted from September 2012 to March 2013
      in the Department of Internal Medicine of a tertiary care hospital situated at
      moderate high altitude (11,500 ft) in India. Materials and Methods: Patients
      admitted with high altitude pulmonary edema (HAPE) were recruited by convenience
      sampling. The ONSD of both eyes were measured 3 mm behind the globe using a 7.5
      MHz linear probe on the closed eyelids of supine subjects. Statistical Analysis:
      Analysis was done using SPSS 17.0. Results: A total of 47 patients of HAPE were
      recruited to the study with daily ONSD recording of both eyes during the
      admission period. The mean ONSD of the left eye was 4.60 (standard deviation [SD]
      = 0.71) whereas the mean ONSD of right eye 4.59 (SD = 0.72). The ONSD of the
      right eye and left eye was strongly correlated (correlation coefficient = 0.98
      with P < 0.0001). The mean difference in the ONSD of both eyes (right-left) was 
      0.0044 (SD = 0.11) which was not statistically significant (P = 0.533).
      Conclusion: Our results suggest that the difference in ONSD of both eyes is not
      statistically significant in disease or health. This study also suggests that the
      ONSD of either eye can be predicted by the other eye recordings. Based on these
      findings, it can be suggested that during ocular USG for routine bedside/research
      purposes it is sufficient to measure ONSD of any of the one eye to save time and
      avoid discomfort to the patient.

PMID- 29657372
TI  - Targeted Interventions in Critically Ill Children with Severe Dengue.
AB  - Background: The World Health Organization guidelines provide suggestions on early
      recognition and treatment of severe dengue (SD); however, mortality in this group
      can be high and is related both to disease severity and the treatment
      complications. Subjects and Methods: In this prospective observational study, we
      report our results where standard therapy (ST) was enhanced by Intensive Care
      Unit (ICU) supportive measures that have proven beneficial in other conditions
      that share similar pathophysiology of capillary leak and fluid overload. These
      include early albumin for crystalloid-refractory shock, proactive monitoring for
      symptomatic abdominal compartment syndrome (ACS), application of a high-risk
      intubation management protocol, and other therapies. We compared outcomes in a
      matched retrospective cohort who received ST. Results: We found improved outcomes
      using these interventions in patients with the most devastating forms of dengue
      (ST+ group). We could demonstrate decreased positive fluid balance on days 1-3
      and less symptomatic ACS that necessitated invasive percutaneous drainage (7.7%
      in ST+ group vs. 30% in ST group, P = 0.025). Other benefits in ST+ group
      included lower intubation and positive pressure ventilation requirements (18.4%
      in ST+ vs. 53.3% in ST, P = 0.003), lower incidence of major hemorrhage and acute
      kidney injury, and reduced pediatric ICU stays and mortality (2.6% in ST+ group
      vs. 26% in ST group, P = 0.004). Conclusion: Children with SD with refractory
      shock are at extremely high mortality risk. We describe the proactive application
      of several targeted ICU supportive interventions in addition to ST and could show
      that these interventions resulted in decreased resuscitation morbidity and
      improved outcomes in SD.

PMID- 29657373
TI  - Severe Varicella Pneumonia in Adults: Seven Years' Single-center Experience from
      India.
AB  - Context: Varicella pneumonia is a rare but a serious complication of chickenpox
      in adults. There is paucity of data on varicella pneumonia from India. Aims: The
      aim of this study is to describe the clinical manifestations, hospital course,
      treatment, and outcome of adult patients with severe varicella pneumonia.
      Settings and Design: This was a retrospective, observational study of patients
      with severe varicella pneumonia attending a tertiary care teaching hospital.
      Subjects and Methods: The cases of varicella were identified by a computerized
      search of the medical record for the period between January 2010 and December
      2016. During this period, 137 patients got admitted with varicella of which 22
      had severe varicella pneumonia. Statistical Analysis: Mean and standard deviation
      were computed. Fisher's Z-test of proportions and analysis of variance were
      applied. Results: There were 17 (77.3%) men and 5 (22.7%) women. The mean age of
      the patients was 33.4 +/- 10.8 years. History of contact with an infected person
      followed by high-grade fever and typical rash was present in all patients. Forty
      five percent (10/22) of patients were immunosuppressed. All the patients received
      intravenous acyclovir. Forty-five percent (10/22) of patients received invasive
      mechanical ventilation. The various factors associated with the need for
      mechanical ventilation were partial pressure of oxygen:fraction of inspired
      oxygen ratio <150, quick sequential (sepsis-related) organ failure assessment
      (qSOFA) >2, and early bacterial coinfection. The mean Intensive Care Unit and
      hospital stay were 7 days (range; 1-16) and 9 days (range; 4-21), respectively.
      The overall mortality was 22.7% and reached 50% in those requiring invasive
      ventilation. The mortality was higher among patients with qSOFA >3, mean arterial
      blood pressure <60 mmHg, and severe acute respiratory distress syndrome at
      presentation. Conclusions: Patients with severe varicella pneumonia are at an
      increased risk of respiratory failure and death.

PMID- 29657374
TI  - Methylene Blue for Vasoplegic Syndrome Postcardiac Surgery.
AB  - Objectives: cardiopulmonary bypass (CPB) can be complicated by vasoplegia that is
      refractory to vasopressors. Methylene blue (MB) represents an alternative in such
      cases. Patients and Methods: Retrospective observational historical control
      matched study. From 2010 to 2015, all patients who received MB for vasoplegia
      post-CPB were included in this study. Historical controls from the period of 2004
      to 2009 were matched. End-points were the time till improvement of vasoplegia
      (Ti), 30-day mortality, cardiac surgical Intensive Care Unit (CSICU) morbidity,
      and length of stay (LOS). Results: Twenty-eight patients were matched in both
      groups. There were no statistically significant differences between the two
      groups in demographic, laboratory data on admission, or hemodynamic profile
      before use of MB. Ti and time to complete discontinuation of vasopressors were
      statistically significant less in MB group (8.2 +/- 2.6 vs. 29.7 +/- 6.4, P =
      0.00 and 22.6 +/- 5.2 vs. 55.3 +/- 9.4, P = 0.00) respectively. Mortality at day
      30 was significantly higher in controls compared to MB (1 patient [3.6%] vs. 6
      patients [21.4%], long rank P = 0.04). CSICU, hospital LOS, and incidence of
      renal failure was significantly higher in control group (12.4 +/- 3.7 vs. 7 +/-
      1.4, P = 0.03), (19.5 +/- 2.4 vs. 10.9 +/- 3.2, P = 0.05) and (9 patients [32.1%]
      vs. 2 patients [7.1%], P = 0.04), respectively. Duration of mechanical
      ventilation was less in MB patients; however, did not reach statistical
      significance. Conclusions: the use of MB for vasoplegia postcardiac surgery was
      associated with rapid recovery of hemodynamics, shorter need for vasopressors,
      less ICU mortality, less incidence of renal failure, and shorter LOS.

PMID- 29657375
TI  - Comparison of Glycemic Control between Continuous Regular Insulin Infusion and
      Single-dose Subcutaneous Insulin Glargine Injection in Medical Critically Ill
      Patients.
AB  - Background and Aims: This study aimed to compare glycemic control between
      continuous intravenous regular insulin infusion and single-dose subcutaneous
      insulin glargine injection in medical critically ill patients. Subjects and
      Methods: A prospective noninferiority study was conducted in medical critically
      ill patients who developed hyperglycemia and required regular insulin infusion by
      the Intensive Care Unit glycemic control protocol. The eligible patients were
      switched from the daily regular insulin requirement to single-dose subcutaneous
      insulin glargine injection by a 100% conversion dose. Arterial blood glucose was
      checked every 2 h for 24 h. Success cases were blood glucose levels of 80-200
      mg/dL during the study period. The mean time-averaged area under the curves
      (AUCs) of blood glucose levels between the two types of insulin were compared by
      t-test. Results: Of 20 cases, 14 cases (70%) were successful. The mean time
      averaged AUCs of blood glucose levels between the two types of insulin were not
      significantly different (155.91 +/- 27.54 mg/dL vs. 151.70 +/- 17.07 mg/dL, P =
      0.56) and less than the predefined noninferior margin. No severe hypoglycemic
      cases were detected during the study period. Conclusions: Single-dose
      subcutaneous insulin glargine injection was feasibly applied for glycemic control
      in medical critically ill patients. The glycemic control in the critically ill
      patients by a single dose of subcutaneous insulin glargine was comparable to
      standard intravenous regular insulin infusion. A conversion dose of 100% of the
      daily requirement of regular insulin is suggested.

PMID- 29657377
TI  - Failure of Postexposure Prophylaxis in a Patient Given Rabies Vaccine
      Intramuscularly in the Gluteus Muscle, Himachal Pradesh, India.
AB  - A 48-year-old male was bitten by a dog on the forehead and on the RIGHT side of
      left eyebrow on November 26, 2017, at 2 pm. The patient was immediately rushed to
      a nearby private hospital where an MBBS doctor gave him immediate wound wash with
      soap and water and prescribed five doses of rabies vaccine intramuscularly (IM).
      Since the patient weight was 60 kg, he was also prescribed 2400 IU of equine
      rabies immunoglobulin (ERIG), but as eRIG was not available, it was not
      administered. All the four doses of rabies vaccine were given IM in gluteus
      muscle. On December 17, 2017, the patient was brought to the Government Regional
      Hospital Hamirpur with the symptoms of difficulty in swallowing water
      (Hydrophobia) for 2 days. He was given injection diazepam and referred to
      Rajinder Prasad Government Medical College Tanda, Kangra, Himachal Pradesh,
      India, where he died of suspected rabies on December 19, 2017. The explicit
      consent to publish this report and picture was taken from the relatives of the
      patient, so that others have a lesson from this case report.

PMID- 29657376
TI  - Smoke Inhalation Injury: Etiopathogenesis, Diagnosis, and Management.
AB  - Smoke inhalation injury is a major determinant of morbidity and mortality in fire
      victims. It is a complex multifaceted injury affecting initially the airway;
      however, in short time, it can become a complex life-threatening systemic disease
      affecting every organ in the body. In this review, we provide a summary of the
      underlying pathophysiology of organ dysfunction and provide an up-to-date survey
      of the various critical care modalities that have been found beneficial in caring
      for these patients. Major pathophysiological change is development of edema in
      the respiratory tract. The tracheobronchial tree is injured by steam and toxic
      chemicals, leading to bronchoconstriction. Lung parenchyma is damaged by the
      release of proteolytic elastases, leading to release of inflammatory mediators,
      increase in transvascular flux of fluids, and development of pulmonary edema and
      atelectasis. Decreased levels of surfactant and immunomodulators such as
      interleukins and tumor-necrosis-factor-alpha accentuate the injury. A primary
      survey is conducted at the site of fire, to ensure adequate airway, breathing,
      and circulation. A good intravenous access is obtained for the administration of
      resuscitation fluids. Early intubation, preferably with fiberoptic bronchoscope,
      is prudent before development of airway edema. Bronchial hygiene is maintained,
      which involves therapeutic coughing, chest physiotherapy, deep breathing
      exercises, and early ambulation. Pharmacological agents such as beta-2 agonists,
      racemic epinephrine, N-acetyl cysteine, and aerosolized heparin are used for
      improving oxygenation of lungs. Newer agents being tested are perfluorohexane,
      porcine pulmonary surfactant, and ClearMate. Early diagnosis and treatment of
      smoke inhalation injury are the keys for better outcome.

PMID- 29657378
TI  - Lung Collapse Secondary to Massive Pericardial Effusion in Adults: Two Case
      Reports.
AB  - We present two cases of respiratory insufficiency due to left lung collapse
      secondary to massive pericardial effusion. Both patients had pericardial effusion
      due to their underlying disease. Radioimaging showed compression of the left
      bronchus. Patients got symptomatic relief after pericardiocentesis. Follow-up
      imaging showed expansion of the lung.

PMID- 29657379
TI  - A Clinical Conundrum Called Amitraz Poisoning - A Case Report.
AB  - Amitraz is a nonsystemic insecticide and acaricide which is sometimes also used
      as scabicide. Due to its widespread use, amitraz poisoning has emerged during the
      past decade and a half although the literatures on human intoxication cases are
      scarce. Amitraz poisoning can present with numerous symptoms involving central
      nervous, cardiovascular, and respiratory systems. The mainstay of treatment is
      supportive and symptomatic. We present the case of a 60-year-old gentleman who
      was shifted from another hospital in unconscious state with an alleged history of
      consumption of an unknown substance which later was known to be amitraz.

PMID- 29657380
TI  - Preprocedural Check of Central Venous Catheter Set.

PMID- 29657381
TI  - Risk Factors and Outcome of Acute Kidney Injury after Congenital Heart Surgery.

PMID- 29657382
TI  - Rabies Treatment: Are We Anywhere Close to Cure?

PMID- 29657383
TI  - Symmetrical Gangrene in Both Lower Limbs in Pneumococcal Pneumonia.

PMID- 29657384
TI  - Quiz Answers.

PMID- 29657385
TI  - Quiz Section.

PMID- 29657386
TI  - Developmental programming of the pancreatic islet by in utero overnutrition.
AB  - The Developmental Origins of Health and Disease (DOHaD) Hypothesis postulates
      that the in utero environment influences postnatal health and plays a role in
      disease etiology. Studies in both humans and animal models have shown that
      exposure to either under- or overnutrition in utero results in an increased risk
      of metabolic disease later in life. In addition, offspring born to overweight or
      obese mothers are more likely to be obese as children and into early adulthood
      and to have impaired glucose tolerance as adults. The Centers for Disease Control
      and Prevention estimates that over 70% of adults over the age of 20 are either
      overweight or obese and that nearly half of women are either overweight or obese
      at the time they become pregnant. Thus, the consequences of maternal
      overnutrition on the developing fetus are likely to be realized in greater
      numbers in the coming decades. This review will focus specifically on the effects
      of in utero overnutrition on pancreatic islet development and function and how
      the resulting morphological and functional changes influence the offspring's risk
      of developing metabolic disease. We will discuss the advantages and challenges of
      different animal models, the effects of exposure to overnutrition during distinct
      periods of development, the similarities and differences between and within model
      systems, and potential mechanisms and future directions in understanding how
      developmental alterations due to maternal diet exposure influence islet health
      and function later in life.

PMID- 29657387
TI  - Anti-inflammatory activity of Jatropha curcas Linn. latex in cream formulation on
      CD68 expression in mice skin wound.
AB  - Aim: The purpose of the present study was to determine the potential of Jatropha
      curcas latex in the cream formulation on CD68 immune expression (macrophages)
      during inflammatory phase wound healing process in mice skin. Materials and
      Methods: Amount of 12 two-months-old male mice were used between 30 and 40 g. To
      surgical procedures, wound skin incision was performed 2.0 cm in length until
      subcutaneous on the paravertebral of each animal. The treatment was carried under
      locally anesthetized with procaine cream. The mice were allotted into four groups
      of each, entire surface of each group wound covered by base cream control,
      sulfadiazine 0.1% cream, J. curcas latex cream 10% and, 15%, respectively. All
      experiments were performed twice a day for 3 days. The wound healing was assayed
      in stained histological sections in immunohistochemical of the wounds. CD68
      expression was investigated under a microscope. Results: The results showed that
      the cream from the 10% and 15% latex of J. curcas revealed moderate immune
      reaction to CD68 on wound healing. Conclusion: We concluded that the latex cream
      of J. curcas possesses anti-inflammatory activity in wound healing process of
      mice skin.

PMID- 29657388
TI  - Occurrence and quantification of Shiga toxin-producing Escherichia coli from food
      matrices.
AB  - Aim: The objective of the study was to detect Shiga toxin-producing Escherichia
      coli (STEC) and develop a quantitative polymerase chain reaction (qPCR) assay to
      quantify the bacterial DNA present in different food matrices. Materials and
      Methods: A total of 758 samples were collected during a period from January 2015
      to December 2016 from Kozhikode, Thrissur, and Alappuzha districts of Kerala. The
      samples consisted of raw milk (135), pasteurized milk (100), beef (132), buffalo
      meat (130), chevon (104), beef kheema (115), and beef sausage (42). All the
      samples collected were subjected to isolation and identification of STEC by
      conventional culture technique. Confirmation of virulence genes was carried out
      using PCR. For the quantification of STEC in different food matrices, a qPCR was
      standardized against stx1 gene of STEC by the construction of standard curve
      using SYBR green chemistry. Results: The overall occurrence of STEC in raw milk
      (n=135), beef (n=132), buffalo meat (n=130), chevon (n=104), and beef kheema
      (n=115) samples collected from Kozhikode, Thrissur, and Alappuzha districts of
      Kerala was 19.26%, 41.6%, 16.92%, 28.85%, and 41.74%, respectively. PCR revealed
      the presence of stx 1 and stx 2 genes in 88.46 and 83.64 and 30.77 and 40.00% of
      STEC isolates from raw milk and beef samples, respectively, while 100% of the
      STEC isolates from buffalo beef and beef kheema samples carried stx 1 gene. Real
      time qPCR assay was used to quantify the bacterial cells present in different
      food matrices. The standard curve was developed, and the slopes, intercept, and
      R2 of linear regression curves were -3.10, 34.24, and 0.99, respectively.
      Conclusion: The considerably high occurrence of STEC in the study confirms the
      importance of foods of animal origin as a vehicle of infection to humans. In the
      present study, on comparing the overall occurrence of STEC, the highest
      percentage of occurrence was reported in beef kheema samples. The study shows the
      need for rigid food safety measures to combat the potential pathogenic effects of
      harmful bacteria throughout the production chain from production to consumption.

PMID- 29657389
TI  - Hepato nephropathology associated with inclusion body hepatitis complicated with
      citrinin mycotoxicosis in a broiler farm.
AB  - Aim: Mortality in a broiler chicken farm was investigated for identifying the
      cause of mortality. Materials and Methods: A broiler farm with a population of
      16000 succumbed to a disease outbreak. Clinical signs, vaccination history and
      mortality, were recorded. Necropsy examination and microscopic examination were
      carried out along with toxicological and molecular studies. Results: The clinical
      signs in the affected broiler birds were of non-specific nature with a total
      mortality of 26.39%. Postmortem examination and microscopical findings revealed
      hepatitis with basophilic intranuclear inclusion, splenitis, myocarditis, and
      nephritis. Glomerulonephritis was the prominent renal pathology recorded in this
      study. Polymerase chain reaction test confirmed the presence of fowl adenovirus
      (FAdV) genome in the target organs, and toxicological examination by thin-layer
      chromatography revealed the presence of a toxic level of citrinin in the feed
      samples. Conclusion: Based on various diagnostic investigations, the mortality in
      the flock was attributed to inclusion body hepatitis (IBH) complicated with
      citrinin mycotoxicosis. Thus, apart from liver pathology which occurs in a
      classical IBH cases, glomerulonephritis too occurs which are also a prominent
      finding which pathologists often miss. Thus, kidneys should also be examined
      histologically to assess the microscopic tissue alterations in poultry suspected
      for IBH along with a mycotoxicological analysis of feed. This will definitely
      throw light on the synergistic pathology elicited and exhibited by FAdV and
      mycotoxins in the poultry.

PMID- 29657390
TI  - Market potential and opportunities for commercialization of traditional meat
      products in North East Hill Region of India.
AB  - The North Eastern (NE) India is renowned for its preference for animal-based
      food. This region is known for its traditional meat products. However, the
      popularity of these products remains confined to the specific community/location.
      The knowledge on the traditional preparation methods is generally passed across
      generations through practice and word of mouth. The traditional style of
      preparation and the specific ingredients added to each product makes them unique.
      In this review, an attempt has been made to identify the initiatives,
      opportunities, and market potential for commercialization of the traditional meat
      products. These unique features and properties of the traditional meat products
      have been highlighted. The commercialization of these products will enhance
      entrepreneurship development and ensure quality ethnic products to the consumer
      in the NE hill region of India.

PMID- 29657391
TI  - Bacteriological cure rate and changes in milk composition in mastitis vaccinated
      ewes affected with subclinical mastitis.
AB  - Aim: The aim of this study was to investigate the effects of using a commercially
      available polyvalent mastitis vaccine on the bacteriological cure rate of
      existing subclinical mastitis in Awassi sheep. Materials and Methods: A total of
      164 lactating ewes were divided into two main groups according to udder health
      and milk somatic cell count (SCC): Group 1=normal (N; n=80) and Group
      2=subclinical mastitis (SC; n=84). Each group was then subdivided randomly into
      two treatment groups: N vaccinated (Nvax; n=38), N non-vaccinated (Nnvax; n=42),
      SC vaccinated (SCvax; n=42), and SC non-vaccinated (SCnvax; n=42). The vaccine
      was administered as per manufacturer's recommendations. Milk samples were
      collected aseptically from all ewes before vaccine administration (T0) and again
      on days 28 (T2) and 42 (T3) of the experiment. Results: In the SC group, the
      bacteriological cure rates in vaccinated and non-vaccinated ewes were 76% and
      69%, respectively. In N group, the new intramammary infection rates in vaccinated
      and non-vaccinated ewes were 48% and 50%, respectively. Vaccination of normal
      ewes resulted in a significant (p<0.05) reduction in bacterial growth rate both
      at day 28 and day 42 of the study. The prevalence of new intramammary infection
      rate in Nvax ewes on days 28 and 42 was 19% and 20%, respectively. The prevalence
      of new intramammary infection rate in Nnvax group on days 28 and 42 was 33% and
      30%, respectively. In SCvax group, the bacterial growth rate on days 28 and 42
      was 44% and 35%, respectively. In SCnvax group, the bacterial growth rate on days
      28 and 42 was 27% and 32%, respectively. There was no statistically significant
      effect of vaccination on any of the studied milk composition parameters.
      Conclusions: This is a preliminary study that indicated a possible protective
      effect of vaccination against mastitis in sheep. Further, case-controlled studies
      are indicated to estimate the level of immunity this vaccine provides to
      vaccinated sheep.

PMID- 29657392
TI  - Effect of exogenous melatonin and different photoperiods on oxidative status and
      antioxidant enzyme activity in Chhotanagpuri ewe.
AB  - Aim: The present study was conducted to evaluate the effect of exogenous
      melatonin under different photoperiods on oxidative status in Chhotanagpuri ewe.
      Materials and Methods: A total of 42 non-pregnant, non-lactating Chhotanagpuri
      ewe, having body weight ranging between 14.11+/-0.09 and 15.38+/-0.06 kg, were
      selected and were isolated from rams 2 months before melatonin administration.
      The selected animals were allocated randomly into seven groups, namely, Group I
      (normal control), Group II (long day [LD] control), Group III (LD+melatonin
      administration orally, 3 mg/day), Group IV (LD+melatonin administration
      subcutaneously, 1 mg/day), Group V (short day [SD] control), Group VI
      (SD+melatonin administration orally, 3 mg/day), and Group VII (SD+melatonin
      administration subcutaneously, 1 mg/day) comprising six animals in each group.
      Rams were then introduced into each group after completion of exogenous
      administration of melatonin. Blood samples with anticoagulant in vials were
      collected from each animal day before the start of the experiment and thereafter
      every month up to 5th month. Hemolysate was prepared for estimation of oxidative
      stress parameters such as malondialdehyde (MDA), superoxide dismutase (SOD), and
      catalase (CAT). Results: It was observed that the level of MDA was significantly
      (p<0.05) higher in LD groups (Group II, III and IV) in comparison to control and
      SD groups (VI and VII) at 1st month. MDA concentration after exogenous
      administration of melatonin was significantly (p<0.05) decreased in Group IV and
      VI in comparison to 1st month. SOD was significantly (p<0.05) higher in SD groups
      (V, VI, and VII) at the 1st month in comparison to 0 day. After exogenous
      administration of melatonin, SOD concentration was significantly (p<0.05) higher
      in Groups III and IV in comparison to 1st month. CAT was significantly (p<0.05)
      higher in SD groups (V, VI, and VII) in comparison to control and LD groups.
      After exogenous administration of melatonin, CAT concentration was significantly
      (p<0.05) higher in Groups III, IV, VI, and VIII in comparison to Groups I, II,
      and V. At the 3rd month, CAT concentration significantly (p<0.05) decreased in
      Groups III, IV, VI, and VII in comparison to 2nd month of experiment. However, a
      decreasing trend of CAT was observed in all the groups from 3rd to 5th month.
      Conclusion: The present experiment revealed that exogenous melatonin was able to
      reduce significantly the level of MDA and increased the activity of SOD and CAT
      in Chhotanagpuri ewe.

PMID- 29657393
TI  - The analysis of hippocampus neuronal density (CA1 and CA3) after Ocimum sanctum
      ethanolic extract treatment on the young adulthood and middle age rat model.
AB  - Aim: This study aimed to assess the changes in neuronal density in CA1 and CA3
      regions in the hippocampus of young adulthood and middle age rat model after
      feeding by Ocimum sanctum ethanolic extract. Materials and Methods: In this
      research, 30 male Wistar rats consist of young to middle-aged rats were divided
      into three groups (3, 6, and 9 months old) and treated with a different dosage of
      O. sanctum ethanolic extract (0, 50, and 100 mg/kg b.w.) for 45 days.
      Furthermore, cresyl violet staining was performed to analyze hippocampus
      formation mainly in CA1 and CA3 area. The concentrations of acetylcholine (Ach)
      in brain tissues were analyzed by enzyme-linked immunosorbent assay. Results: In
      our in vivo models using rat model, we found that the administration of O.
      sanctum ethanolic extract with a dosage of 100 mg/kg b.w. for 45 days induced the
      density of pyramidal cells significantly in CA1 and CA3 of the hippocampus. These
      results were supported by an increase of Ach concentrations on the brain tissue.
      Conclusions: The administration of O. sanctum ethanolic extract may promote the
      density of the pyramidal cells in the CA1 and CA3 mediated by the up-regulated
      concentration of Ach.

PMID- 29657394
TI  - Ethnoveterinary treatments for common cattle diseases in four districts of the
      Southern Province, Zambia.
AB  - Aim: Ethno veterinary knowledge has rarely been recorded, and no or limited
      effort has been made to exploit this knowledge despite its widespread use in
      Zambia. This study documented the types of plants used to treat important animal
      diseases in rural Zambia as a way of initiating their sustained documentation and
      scientific validation. Materials and Methods: The study was done in selected
      districts of the Southern Zambia, Africa. The research was a participatory
      epidemiological study conducted in two phases. The first phase was a pre-study
      exploratory rapid rural appraisal conducted to familiarize the researchers with
      the study areas, and the second phase was a participatory rural appraisal to help
      gather the data. The frequency index was used to rank the commonly mentioned
      treatments. Results: A number of diseases and traditional treatments were listed
      with the help of local veterinarians. Diseases included: Corridor disease
      (Theileriosis), foot and mouth disease, blackleg, bloody diarrhea, lumpy skin
      disease, fainting, mange, blindness, coughing, bloat, worms, cobra snakebite,
      hemorrhagic septicemia, and transmissible venereal tumors. The plant preparations
      were in most diseases given to the livestock orally (as a drench). Leaves, barks,
      and roots were generally used depending on the plant type. Conclusion: Ethno
      veterinary medicine is still widespread among the rural farmers in the province
      and in Zambia in general. Some medicines are commonly used across diseases
      probably because they have a wide spectrum of action. These medicines should,
      therefore, be validated for use in conventional livestock healthcare systems in
      the country to reduce the cost of treatments.

PMID- 29657395
TI  - Prevalence of liver flukes infections and hydatidosis in slaughtered sheep and
      goats in Nishapour, Khorasan Razavi, Iran.
AB  - Background: Food-borne trematode infections and hydatidosis are endemic diseases
      caused by helminths in Iran that are responsible for great economic loss and
      getting public health at risk. Aim: Aim of this study was to determine the
      prevalence of fasciolosis, dicrocoeliasis, and hydatidosis infections in
      slaughtered sheep and goats in Nishapour, Khorasan Razavi province of Iran.
      Materials and Methods: A survey was implemented on 130,107 sheep and goats
      slaughtered at an abattoir in Nishapour (Neyshbur) city, north central Khorasan
      Razavi Province, Iran, to determine the prevalence of fascioliasis,
      dicrocoeliosis and presence of hydatidosis. Results: During a 1-year period of
      study, among 130,107 of sheep and goats slaughtered at Nishapour abattoir, 1064
      and 7124 livers were condemned totally and partially, respectively. A total of
      255 (0.19%), 181 (0.12 %), and 7751 (5.95%) of livers were condemned due to cysts
      of Echinococcus granulosus, flukes of Fasciola spp., and Dicrocoelium
      dendriticum, respectively. Totally, 1932 (1.48%) lungs were condemned due to
      hydatidosis. The significant seasonal pattern was seen for fasciolosis,
      dicrocoeliosis, and hydatidosis, statistically (p<0.01). Conclusion: According to
      this study, it seems that Neyshabour is considered as an endemic region for
      Fasciola spp. and D. dendriticum infections and D. dendriticum is the most
      widespread liver fluke found in sheep and goats.

PMID- 29657396
TI  - Projected economic losses due to vector and vector-borne parasitic diseases in
      livestock of India and its significance in implementing the concept of integrated
      practices for vector management.
AB  - Broadly, species of arthropods infesting livestock are grouped into flies (biting
      and non-biting), fleas, lice (biting and sucking), ticks (soft and hard), and
      mites (burrowing, non-burrowing, and follicular). Among which, biting and non
      biting flies and ticks are the potent vectors for many bacterial, viral,
      rickettsial, and protozoan diseases. Vectors of livestock are having economic
      significance on three points (1) direct losses from their bite and annoyance,
      worries, and psychological disturbances produced during the act of biting and
      feeding, (2) diseases they transmit, and (3) expenditure incurred for their
      control. Flies such as Culicoides spp. and Musca spp. and various species of hard
      ticks play important role in disease transmission in addition to their direct
      effects. For control of vectors, recent concept of integrated pest management
      (IPM) provides the best solution and also addresses the problems related to
      acaricide resistance and environmental protection from hazardous chemicals.
      However, to successfully implement the concept of IPM, for each vector species,
      estimation of two monitory benchmarks, i.e., economic injury level (EIL) and
      economic threshold level (ETL) is essential prerequisite. For many vector species
      and under several circumstances, estimation of EIL and ETL appears to be
      difficult. Under such scenario, although may not be exact, an approximate
      estimate can be accrued by taking into account several criteria such as percent
      prevalence of vectors in a geographical area, percent losses produced, total
      livestock population, and current prices of livestock products such as milk,
      meat, and wool. Method for approximate estimation is first time described and
      elaborated in the present review article.

PMID- 29657397
TI  - Effect of lipopolysaccharide derived from surabaya isolates of Actinobacillus
      actinomycetemcomitans on alveolar bone destruction.
AB  - Background: Actinobacillus actinomycetemcomitans' lipopolysaccharide (LPS) has a
      high virulence factor. It interacts with serum protein through receptors on the
      epithelial cell surface, thereby increasing both interleukin (IL)-1beta, and IL-6
      which results in damage to periodontal tissue. Aim: The aim of the study was to
      identify and evaluate the effect of LPS derived from local isolates (A.
      actinomycetemcomitans) on the destruction of alveolar bone by means of several
      biomarkers, including; the number of osteoblasts and osteoclasts, the expression
      of IL-6, matrix metallopeptidase 1 (MMP-1), and receptor activator of nuclear
      factor kappa-Beta ligand (RANKL). Materials and Methods: The isolation of LPS
      from A. actinomycetemcomitans was calculated using phenol, while purification was
      performed using Sephadex C-18 column chromatography. 40 Wistar rats were divided
      into four groups of 10. Each treatment was divided into two groups which were
      0.9% NaCl and LPS induced for 7 and 14 days, respectively. Gingival and alveolar
      bones were further introduced into the induction area, followed by the measuring
      of osteoblast and osteoclast with hematoxylin-eosin staining, IL-6, MMP-1 and
      RANKL expression with immunohistochemical. Results: Reduced numbers of
      osteoblasts at the 7th and 14th day of treatment were detected, while those of
      osteoclasts increased. There was an increased expression of IL-6, MMP-1, and
      RANKL in the 7th and 14th-day treatment group. Treatment of LPS from A.
      actinomycetemcomitans over 7 and 14 days resulted in damage to periodontal tissue
      and alveolar bone in Wistar rats. Conclusion: LPS of A. actinomycetemcomitans
      administration for 7 and 14 days causes periodontal and alveolar tissue
      destruction in Wistar rats.

PMID- 29657398
TI  - Effect of temperature (cooking and freezing) on the concentration of
      oxytetracycline residue in experimentally induced birds.
AB  - Aim: The objective of this study was to determine the effect of varying
      temperatures (different cooking methods and freezing) on the concentration of
      oxytetracycline (OTC) residues in tissues of broiler birds. Materials and
      Methods: Fifty, 5-week-old birds were purchased and acclimatized for 3 weeks
      while being fed antibiotic-free feed and water. Four birds were then tested for
      residue and in the absence; the remaining birds were injected intramuscularly
      with oxytetracycline at its therapeutic dose. Muscle and liver samples of the
      treated birds were harvested and checked for OTC residues before subjecting them
      to boiling, microwaving, and roasting. The three plate test was used for the
      residue detection. Result: OTC was detected at both pH 6.0 and pH 7.2 but not
      detected at pH 8.0. Roasting and boiling significantly reduced the concentration
      of oxytetracycline in muscle by 53.6% and 69.6%, respectively, at pH 6.0,
      microwaving reduced the concentration by 49.1% but was not statistically
      significant. The same pattern was followed at pH 7.2 with reduction of 34.3%,
      53.2%, and 67.7% for microwaved, roasted, and boiled. For the liver tissues,
      there was a significant reduction in the concentration for both pH: 6.0 (57.75%,
      79.75%, and 89%; pH 7.2 (48.06%, 79.6%, and 88.79%) for boiled, microwaved, and
      roasted samples. Boiling had a greater reduction effect for muscle samples while
      roasting had a greater reduction in liver samples at both pHs. Freezing at -10
      degrees C had no effect on the concentration of OTC even after 9 days.
      Conclusion: The significant reduction of OTC concentration by cooking indicates
      that consumers may not be at risk of the effects of OTC residues in meat, but
      microwaving meat may not reduce the concentration below the maximum residue limit
      if the initial concentration is very high. Therefore, routine monitoring of drug
      residues in farms and abattoirs is still advocated.

PMID- 29657399
TI  - Seroprevalence of small ruminant caprine arthritis encephalitis lentivirus among
      goats from selected small ruminant farms in Selangor, Malaysia.
AB  - Background and Aim: Caprine arthritis encephalitis (CAE) is an important viral
      disease of small ruminants particularly in dairy goats with severe social and
      economic implication. Hence, this study was designed to determine the
      seroprevalence of CAE virus (CAEV) among goat population in selected small
      ruminant farms in Selangor and the risk factors associated with the occurrence of
      the disease. Materials and Methods: Blood samples were collected from a total of
      91 goats selected at random. Blood serum was harvested and used for competitive
      enzyme-linked immunosorbent assay test to detect antibodies against CAE virus.
      Results: The result obtained showed that 8/91 (8.8%) of the goats were
      seropositive for CAEV. In addition, biosecurity management, source of origin and
      sex of the animal were observed to be important risk factors associated with the
      occurrence of CAE in goats. Conclusion: The findings of this study affirmed that
      the seroprevalence of CAEV infection among goat population in small ruminant
      farms in Selangor, Malaysia, is low. However, there is need to institute strict
      control measures such as testing and culling positive animals or separation of
      infected animals from those that tested negative to the disease for effective
      eradication of the disease.

PMID- 29657400
TI  - The effect of moderate exercise on the elevation of Bax/Bcl-2 ratio in oral
      squamous epithelial cells induced by benzopyrene.
AB  - Aim: The aim of this study was to analyze the effect of moderate exercise on the
      elevation of Bax/Bcl-2 ratio. Materials and Methods: Eighteen Mus musculus strain
      Swiss Webster (Balb/c) were divided into three groups (n=6). K1 and K2 had
      contact with water 3 times/week for 12 weeks, while the members of the K3 group
      swam 3 times/week for 12 weeks while carrying load weighed 3% of their body
      weight. After 5 weeks, they were induced with 0.04 ml oleum olivarum (K1), 0.08
      mg benzopyrene/0.04 ml oleum olivarum (K2, K3) 3 times/week for 4 weeks.
      Immunohistochemistry assays were used to determine the ratio of Bax/Bcl-2
      expression. The results were analyzed using an independent t-test. Result: The
      Bax/Bcl-2 ratio increased significantly in K3 compared to K2 (p=0.00).
      Conclusion: Moderate exercise could increase the Bax/Bcl-2 ratio in oral squamous
      epithelial cells induced by benzopyrene.

PMID- 29657401
TI  - End-threaded intramedullary positive profile screw ended self-tapping pin (Admit
      pin) - A cost-effective novel implant for fixing canine long bone fractures.
AB  - Aim: The current study was undertaken to evaluate the clinical efficacy of end
      threaded intramedullary pinning for management of various long bone fractures in
      canines. Materials and Methods: This study was conducted in two phases, managing
      25 client-owned dogs presented with different fractures. The technique of
      application of end-threaded intramedullary pinning in long bone fractures was
      initially standardized in 6 clinical patients presented with long bone fractures.
      In this phase, end-threaded pins of different profiles, i.e., positive and
      negative, were used as the internal fixation technique. On the basis of results
      obtained from standardization phase, 19 client-owned dogs clinically presented
      with different fractures were implanted with end-threaded intramedullary positive
      profile screw ended self-tapping pin in the clinical application phase. Results:
      The patients, allocated randomly in two groups, when evaluated postoperatively
      revealed slight pin migration in Group-I (negative profile), which resulted in
      disruption of callus site causing delayed union in one case and large callus
      formation in other two cases whereas no pin migration was observed in Group-II
      (positive profile). Other observations in Group-I was reduced muscle girth and
      delayed healing time as compared to Group-II. In clinical application, phase 21st
      and 42nd day post-operative radiographic follow-up revealed no pin migration in
      any of the cases, and there was no bone shortening or fragment collapse in end
      threaded intramedullary positive profile screw ended self-tapping pin.
      Conclusion: The end-threaded intramedullary positive profile screw ended self
      tapping pin used for fixation of long bone fractures in canines can resist pin
      migration, pin breakage, and all loads acting on the bone, i.e., compression,
      tension, bending, rotation, and shearing to an extent with no post-operative
      complications.

PMID- 29657402
TI  - Identification and antibiogram pattern of Bacillus cereus from the milk and milk
      products in and around Jammu region.
AB  - Aim: The aims of the present study were to assess the prevalence, identification,
      and antibiogram pattern of Bacillus cereus from 215 samples of different milk and
      milk products in and around Jammu region. Materials and Methods: In the present
      study, 215 samples of milk, rasgulla, burfi, rasmalai, kalaari, paneer, ice
      cream, and pastry were collected and analyzed for the isolation of the B. cereus
      using PEMBA, and antibiogram pattern was observed for all the milk and milk
      products. Results: B. cereus was detected in 61/215 samples with an overall
      prevalence of 28.37%. Biotyping revealed predominantly 5, 7, and 2 biotypes in
      raw milk. Burfi and ice cream revealed 2, 3, 5, and 7 biotypes. Rasgulla had 2,
      3, and 5 biotypes; paneer and rasmalai had biotypes 2 and 5, while kalaari
      revealed biotype 5. Antibiogram pattern revealed that isolates were highly
      sensitive to gentamicin (100%), intermediate to ampicillin (40.98%), tetracycline
      (31.14%), erythromycin (29.50%), and amoxicillin (26.22%), and high resistance
      against penicillin G (100%). Adulteration of starch was detected in 16.66 % raw
      milk samples. All starch positive samples were positive for B. cereus. However,
      12 starch negative samples also yielded B. cereus. Conclusion: From this study,
      it was concluded that highest prevalence of B. cereus was found in ice cream.
      Several isolates of B. cereus showed toxigenic activity, so the presence of B.
      cereus in milk and milk products may be of public health hazard. The antibiogram
      pattern of B. cereus isolates showed sensitivity to gentamicin, ciprofloxacin,
      chloramphenicol, streptomycin, and resistance to penicillin-G and cephalexin. The
      presence of B. cereus in milk and milk products showed a strong association
      besides establishing the fact that starch adulteration can be indicative of the
      presence of B. cereus.

PMID- 29657403
TI  - Antimicrobial peptides of buffalo and their role in host defenses.
AB  - Antimicrobial peptides (AMPs) are highly conserved components of the innate
      immune system found among all classes of life. Buffalo (Bubalus bubalis), an
      important livestock for milk and meat production, is known to have a better
      resistance to many diseases as compared to cattle. They are found to express many
      AMPs such as defensins, cathelicidins, and hepcidin which play an important role
      in neutralizing the invading pathogens. Buffalo AMPs exhibit broad-spectrum
      antimicrobial activity against both Gram-positive and Gram-negative bacteria.
      Similar to its natural form, synthetic analogs of buffalo AMPs are also
      antimicrobial against bacteria and even fungus making them a good target for the
      development of therapeutic antimicrobials. In addition to its antimicrobial
      effect, AMPs have been demonstrated to have a number of immunomodulatory
      functions, and their genes are responsive to infections. Further, induction of
      their gene expression by external factors may help in preventing infectious
      diseases. This review briefly discusses the AMPs of buffalo identified to date
      and their possible role in innate immunity.

PMID- 29657404
TI  - Comparison of four polymerase chain reaction assays for the detection of Brucella
      spp. in clinical samples from dogs.
AB  - Aim: This study aimed to compare the sensitivity (S), specificity (Sp), and
      positive likelihood ratios (LR+) of four polymerase chain reaction (PCR) assays
      for the detection of Brucella spp. in dog's clinical samples. Materials and
      Methods: A total of 595 samples of whole blood, urine, and genital fluids were
      evaluated between October 2014 and November 2016. To compare PCR assays, the gold
      standard was defined using a combination of different serological and
      microbiological test. Bacterial isolation from urine and blood cultures was
      carried out. Serological methods such as rapid slide agglutination test, indirect
      enzyme-linked immunosorbent assay, agar gel immunodiffusion test, and buffered
      plate antigen test were performed. Four genes were evaluated: (i) The gene coding
      for the BCSP31 protein, (ii) the ribosomal gene coding for the 16S-23S intergenic
      spacer region, (iii) the gene coding for porins omp2a/omp2b, and (iv) the gene
      coding for the insertion sequence IS711. Results: The results obtained were as
      follows: (1) For the primers that amplify the gene coding for the BCSP31 protein:
      S: 45.64% (confidence interval [CI] 39.81-51.46), Sp: 95.62% (CI 93.13-98.12),
      and LR+: 10.43 (CI 6.04-18); (2) for the primers that amplify the ribosomal gene
      of the 16S-23S rDNA intergenic spacer region: S: 69.80% (CI 64.42-75.18), Sp:
      95.62 % (CI 93.13-98.12), and LR+: 11.52 (CI 7.31-18.13); (3) for the primers
      that amplify the omp2a and omp2b genes: S: 39.26% (CI 33.55-44.97), Sp: 97.31%
      (CI 95.30-99.32), and LR+ 14.58 (CI 7.25-29.29); and (4) for the primers that
      amplify the insertion sequence IS711: S: 22.82% (CI 17.89 - 27.75), Sp: 99.66%
      (CI 98.84-100), and LR+ 67.77 (CI 9.47-484.89). Conclusion: We concluded that the
      gene coding for the 16S-23S rDNA intergenic spacer region was the one that best
      detected Brucella spp. in canine clinical samples.

PMID- 29657405
TI  - Immunomodulatory effects of probiotics and prilled fat supplementation on immune
      genes expression and lymphocyte proliferation of transition stage Karan Fries
      cows.
AB  - Background and Aim: Probiotics are the living microorganism which when
      administered improves the digestion and health of the animal. Saccharomyces
      cerevisiae (SC) improves the humoral and innate immunity of the animal. Prilled
      fat is a hydrogenated palm oil triglyceride which has been reported to promote
      the release of cytokines from macrophages. The aim of the study was to evaluate
      the immunomodulatory effect of probiotic and prilled fat during transition stage
      in Karan Fries (KF) cows. Materials and Methods: A total of 12 KF cows at 21 days
      prepartum were selected and divided into two groups of six animals each. The
      control group was fed as per the standard feeding practices and the supplemented
      group cows were supplemented daily with prilled fat at 100 g/cow, SC at 25 g/cow,
      and sweetener at 1 g/cow in addition to the standard feeding practices from -30
      days of prepartum to 21 days of lactation. The sweetener was added to improve the
      palatability of the feed. The natural sweetener of an African plant leave had 105
      times more sweetness than glucose with good aroma. The dry matter intake of the
      animal was recorded. Plasma samples were collected weekly from all cows for the
      analysis of blood metabolite beta-hydroxybutyric acid (BHBA). Lymphocytes were
      isolated from the blood for studying the expression of tumor necrosis factor
      alpha (TNF-alpha) and interleukin-1beta (IL-1beta) and for estimating lymphocyte
      proliferation index (LPI). Results: The upregulated IL-1beta and TNF-alpha around
      calving might be possibly associated to the metabolic changes occurring during
      the transition period and suggest a higher degree of inflammation around
      parturition. High concentrations of BHBA caused increased expression and
      synthesis of the pro-inflammatory factors such as TNF-alpha and IL-1beta in
      supplemented group in primary calf hepatocytes. The LPI was higher in
      supplemented group as compared to control which suggests a stimulatory effect of
      unsaturated fatty acids on mitogen-stimulated T-cell proliferation. Conclusion:
      Dietary supplementation of probiotics, prilled fat, and sweetener alleviated
      negative energy balance by stimulating feed intake and modulating hepatic lipid
      metabolism; and both of these additives improved the postpartum health
      (antioxidant status and immune function) of transition dairy cows.

PMID- 29657406
TI  - Comparative ovicidal activity of Moringa oleifera leaf extracts on Fasciola
      gigantica eggs.
AB  - Background: Fasciolosis is an important zoonotic disease affecting the productive
      performance of farm animals in Egypt. Aim: The aim of the present study was
      comparing the ovicidal effect of different extracts as an alcoholic (Methanolic
      and Ethanolic) and aqueous Moringa oleifera leaf extracts on Fasciola gigantica
      non-embryonated and developed eggs. Materials and Methods: Tested concentrations
      of extracts ranged from 12.5 to 800 mg/ml. Nitroxynil was used as reference drug
      with a dose of 100 mg/ml. Results: M. oleifera alcoholic and aqueous extracts
      showed a concentration-dependent ovicidal effect on F. gigantica non-embryonated
      and developed eggs. Based on LC50 values, water extract showed the highest
      ovicidal activity since it registered the lowest values of 2.6 mg/ml on non
      embryonated eggs. Non-embryonated eggs were more susceptible to aqueous extract
      than developed eggs. On the other hand, the developed eggs were more susceptible
      to ethanolic extract than non-embryonated eggs even the lowest LC50 (12.38
      mg/ml). Conclusion: M. oleifera leaf extracts especially aqueous extract could be
      a promising step in the field of controlling fascioliasis. Further, in vivo
      studies are needed to enlighten the therapeutic potential of M. oleifera extracts
      in treating F. gigantica infection.

PMID- 29657407
TI  - Intranasal administration of inactivated avian influenza virus of H5N1 subtype
      vaccine-induced systemic immune response in chicken and mice.
AB  - Aim: The need for non-parenteral administration of inactivated avian influenza
      virus of H5N1 subtype (AIV-H5N1) vaccine is paramount. Here, we provide
      preliminary data on the immune response of chicken and mice after intranasal
      administration of AIV-H5N1-inactivated vaccine with ISCOMS, Inmunair (INM), and
      combined ISCOMS and INM as an adjuvant. Materials and Methods: The AIV isolate of
      A/Chicken/Denpasar/01/2004 (H5N1) was cultivated in specific pathogen-free
      chicken eggs and inactivated with formaldehyde. The vaccine preparation was added
      with those adjuvants for intranasal administration and aluminum hydroxide for
      subcutaneous injection. The chicken and mouse were vaccinated at the age of 3
      weeks or 1 month and repeated 2 weeks thereafter. In one experiment, chicken was
      injected with Newcastle disease virus (NDV) at the same time with AIV vaccine.
      The sera were collected at one (serum 1) and 2 w (serum 2) after booster
      vaccination. The anti-AIV-H5 and NDV antibodies in chicken sera were detected
      using hemagglutination inhibition (HI) assay. Mouse IgG anti-AIV-H5N1 antibody
      was detected using ELISA. Results: The result shows that the geometric mean
      titers (GMTs) of chicken sera of intranasal vaccinated with inactivated AIV-H5N1
      vaccine with mixed ISCOM- INM as adjuvant were <20.0 and 22.7 unit HI-unit (HIU)
      in serum 1 and serum 2, respectively. The GMTs of the positive control group were
      23.7 and 25.7 HIU in serum 1 and serum 2, respectively. The result of the second
      experiment shows that IgG anti-AIV-H5N1 was detected in mouse sera. In the third
      experiment, the GMTs of anti-NDV in chicken vaccinated subsequently with
      inactivated NDV vaccine and AIV-H5N1 with mixed ISCOMS-INM administrated
      intranasally and aluminum hydroxide adjuvant administrated through subcutaneous
      injection as well as positive control group receiving NDV vaccine only were 28.0,
      28.0, and 27.4 HIU in serum 1 while were 29.6, 29.2, and 28.2 HIU in serum 2,
      respectively. Conclusion: Intranasal administration of inactivated AIV-H5N1
      vaccine-induced a systemic immune response in chicken and mice after adding
      ISCOMS and/or INM as adjuvants. The adjuvant and the intranasal administration
      caused no immunosuppressive effect on the chicken immune response to NDV vaccine.

PMID- 29657408
TI  - Interspecies comparison of probiotics isolated from different animals.
AB  - Aim: The aim of the current study was to isolate and identify naturally occurring
      probiotic Lactobacillus species in different animals with the different
      environmental background including fish, and farm animals to investigate
      interspecies differences in probiotics on the species level. Materials and
      Methods: A total of 44 fecal and milk samples were collected under aseptic
      conditions from cattle, buffalo, camel, sheep, goats, and fish. The samples were
      cultured, and the isolated strains were confirmed biochemically and molecularly
      using 16S rRNA multiplex polymerase chain reaction (PCR) analysis following DNA
      extraction from the bacterial isolates. Results: A total of 31 isolates
      identified as lactobacilli were isolated from cattle milk, goat feces, sheep
      feces, fish feces, buffalo milk, camel milk, and goats' milk. Lactobacillus
      species were identified based on the size of the PCR product. The results showed
      that different species were different in their lactobacilli content. At the same
      time, there were some differences between individuals of the same species.
      Conclusion: The diversity of probiotic strains isolated from different animal
      species implies different types of benefits to the host. Although it would be
      both money - and time-consuming research, discovering the benefit of each of
      these strains may provide very important information for the health of both human
      and animal. Furthermore, transferring these beneficial effects either to
      individuals within the same species or between different species would be of
      great importance.

PMID- 29657409
TI  - DNA extraction from hydatid cyst protoscolices: Comparison of five different
      methods.
AB  - Aim: The current study aimed to find out a simple, practical and high throughput
      DNA isolation method for extraction of DNA from hydatid cyst samples. Materials
      and Methods: Cattle and sheep isolate of hydatid cysts were obtained from the
      slaughterhouse, and hydatid fluid and protoscolices were collected in a sterile
      condition. Protoscolices were washed, 3 times with phosphate buffered saline, and
      DNA was extracted by different methods including manual extraction with
      freeze/thawing and phenol-chloroform, Triton X-100 extraction, and by a
      commercial kit (YTA, Yekta Tajhiz Azma, Iran) with three different modifications
      in the kit's manufacturer instructions. The obtained DNA from the different
      methods was evaluated by Nanodrop in terms of the yield of DNA and carbohydrates
      or protein contaminations. To compare the quality of the extracted DNA, two
      pieces of the mitochondrial genome of Echinococcus granulosus, cox1, and nad1,
      were polymerase chain reaction (PCR)-amplified, using each of the DNA prepared by
      different methods. Electrophoresis of PCR products was carried out on the agarose
      gel. Results: The DNA extracted by manual method, using phenol/chloroform, had
      the highest yield, yet with the highest level of protein and carbohydrate
      contamination. The DNA extracted using two-step incubations, initially at 60
      degrees C for 2 h and then overnight at 37 degrees C, was the most purified DNA
      with the lowest rate of contamination. Conclusion: Findings of the study
      demonstrated that modification in the currently available commercially DNA
      extraction kit resulted in the development of a high throughput DNA isolation
      method. This method can be recommended for the extraction of DNA from hydatid
      cysts, especially the cattle isolate where the extraction of DNA in these samples
      are usually problematic.

PMID- 29657410
TI  - The effect of purified Quercus cortex extract on biochemical parameters of
      organism and productivity of healthy broiler chickens.
AB  - Aim: Modern methods of producing poultry meat without the use of antibiotics are
      known, and it is possible to achieve the desired conditions, including the use of
      herbal preparations. In addition, it is known that metabolites of medicinal
      plants are inhibitors of the quorum sensing system in bacteria. The aim of the
      present study was to determine the effect of Quercus cortex extract in a reduced
      dose on the productivity and body state of healthy chicken broilers. Materials
      and Methods: For the experiment, 120 heads of 7-day-old healthy broiler chickens
      were selected, and they were divided into four groups (n=30, 3 replicates of 10
      birds in each group) by the analog method. The composition of diets of the
      experimental Groups I and II additionally included Q. cortex extract and Groups
      II and III included an enzyme preparation containing glucoamylase and concomitant
      cellulolytic enzymes. The following methods of study were used; gas
      chromatography-mass spectrometry, mass spectrometry and atomic emission
      spectrometry, and hematological analysis. Results: It was established that the
      increase in live weight of broiler chickens in experimental groups exceeded the
      analogous indicator in the control group by 3.1-16.6%, and feed intake within the
      entire experimental period increased by 2.6-15.4%, against a background of
      decreasing feed consumption for a weight gain of 1 kg of live weight (by 3.7
      9.2%). There was an increase in iron concentration in blood of broiler chickens
      in Groups I and II (7.8-11.8%), in liver (23.7-92.4%, p<=0.05), and in spleen
      (53.9-77.7%, r<=0.05) against the background of a decrease in muscle tissue. A
      decreased content of monocytes and granulocytes was found, especially in
      experimental Group I. Conclusion: In the experiment, it was shown for the first
      time that the inclusion of Q. cortex extract in an enzyme-containing diet (anti
      quarantine substances) was found to increase the productivity of poultry.

PMID- 29657411
TI  - The effect of supplementation of multistrain probiotic preparation in combination
      with vitamins and minerals to the basal diet on the growth performance, carcass
      traits, and physiological response of broilers.
AB  - Aim: The aim of the present study was to investigate the effect of
      supplementation of multistrain probiotic preparation in combination with vitamins
      and minerals to the broiler chicken diets on their growth performance,
      hematological parameters, and carcass traits. Materials and Methods: Two hundred
      and eighty-eight Lohmann 1-day-old broiler chicks were randomly allocated to four
      groups, i.e., control (without additional supplementation) and three experimental
      treatments where basal diet was enriched by 0.1%, 0.5%, or 1% of multistrain
      probiotic preparation in combination with vitamins and minerals, respectively.
      Blood sampling was conducted on day 28, while the selected organs and eviscerated
      carcasses were collected on day 42. Results: Dietary supplementation did not
      affect (p>0.05) the final body weight, feed intake, and feed conversion ratio of
      broilers. Supplementation by 0.1% and 0.5% of multistrain probiotic preparation
      in combination with vitamins and minerals reduced (p<=0.05) heart relative weight
      of broilers. Dietary supplementation tended (p=0.07) to increase the relative
      weight of ileum and pancreas of broilers. Supplemented birds had lower (p<=0.05)
      numbers of leukocytes and eosinophils compared to unsupplemented birds. There
      were tendencies that supplementation of multistrain probiotics in combination
      with vitamins and minerals resulted in lower (p=0.07) counts of lymphocytes and
      heterophils when compared with no supplementation. Supplementation by 0.5% of
      multistrain probiotics in combination with vitamins and minerals resulted in
      lower (p<=0.05) serum concentration of uric acid when compared with control.
      There was no significant effect of dietary supplementation on carcass traits, pH,
      and drip loss of broiler breast muscles. Conclusion: Dietary supplementation of
      commercial broiler feeds with 0.5% of multistrain probiotic preparation in
      combination with vitamins and minerals was potential to improve digestive
      functions and physiological status of broiler chickens.

PMID- 29657412
TI  - Effect of levamisole, Vitamin E, and selenium against aflatoxicosis in broilers
      chicken.
AB  - Aim: The experiment was conducted to determine of levamisole (0.2 ml/kg-BW),
      Vitamin E (80 mg)+selenium (1.6 mg), and aflatoxin (B1) (positive control)
      compared with group without aflatoxin (negative control) on some liver enzymes
      (aspartate transaminase [AST] and alanine transaminase [ALT]), as well as to
      study the histopathological changes. Materials and Methods: The experiment
      included (200) 1-day-old broilers Ross 308 (Turkey source) mixed sexes. They were
      divided into four equal groups (50 chicks each group). The experimental period
      was extended to 35 days. Results: The results revealed that the levels of liver
      enzymes (ALT and AST) of all groups at 35 days were significantly (p<0.05) higher
      than the negative control. Furthermore, the result of histopathological changes
      in thymus and Harderian gland in different ages of group Vitamin E+selenium
      showed a reduction in the depletion of the cortex as well as lessening of
      congestion and hemorrhage and necrosis also decreasing in inflammatory cells in
      the thymus and Harderian gland. Conclusion: The study confirmed the protective
      effect of Vitamin E and levamisole by reducing harmful impacts of aflatoxin
      through their antioxidant effect as they improved the liver enzymes and
      histopathological changes due to the toxin.

PMID- 29657413
TI  - Genetic parameter estimation for pre-weaning growth traits in Jordan Awassi
      sheep.
AB  - Aim: The aim of this study was to estimate the heritability, genetic and
      phenotypic correlations, and the genetic trends for pre-weaning growth traits
      including the birth weight (BWT), weaning weight (WWT), pre-weaning daily gain
      (PWDG), and weaning age (WA) in Awassi lambs. Materials and Methods: A total of
      5131 Awassi lambs from two Jordanian sheep breeding stations were used. A
      multitrait animal model and restricted maximum likelihood methods were used to
      estimate the covariances between the studied traits. Results: The mean+/-standard
      deviation of BWT, WWT, PWDG, and WA was 4.48+/-0.8 kg, 17.13+/-0.7 kg, 0.2+/-0.07
      g, and 65.5+/-0.7 days, respectively. Heritability estimates were 0.30+/-0.04 for
      BWT, 0.19+/-0.04 for WWT and PWDG, and 0.2+/-0.04 for WA. Positive genetic
      correlations were obtained between BWT and other traits, while negative
      correlations were obtained between WWT, PWDG, and WA (-0.50+/-0.12) and between
      WWT and WA (-0.67+/-0.14). The positive phenotypic correlation was obtained
      between WA and PWDG (0.63+/-0.01). The highest additive genetic variance was
      obtained for WA (34.58), while the lowest was estimated for PWDG (6.22E-04). The
      highest phenotypic variance was obtained for WA (175.5), while the lowest value
      obtained was for BWT (0.54). Maternal additive variance ranged between 0.13 and
      0.03. The genetic trends were around zero for all studied traits. Conclusion:
      Selection should be conducted using animals with high estimated breeding values
      through controlled breeding.

PMID- 29657414
TI  - Modeling the potential risk factors of bovine viral diarrhea prevalence in Egypt
      using univariable and multivariable logistic regression analyses.
AB  - Aim: The present cross-sectional study was conducted to determine the
      seroprevalence and potential risk factors associated with Bovine viral diarrhea
      virus (BVDV) disease in cattle and buffaloes in Egypt, to model the potential
      risk factors associated with the disease using logistic regression (LR) models,
      and to fit the best predictive model for the current data. Materials and Methods:
      A total of 740 blood samples were collected within November 2012-March 2013 from
      animals aged between 6 months and 3 years. The potential risk factors studied
      were species, age, sex, and herd location. All serum samples were examined with
      indirect ELIZA test for antibody detection. Data were analyzed with different
      statistical approaches such as Chi-square test, odds ratios (OR), univariable,
      and multivariable LR models. Results: Results revealed a non-significant
      association between being seropositive with BVDV and all risk factors, except for
      species of animal. Seroprevalence percentages were 40% and 23% for cattle and
      buffaloes, respectively. OR for all categories were close to one with the highest
      OR for cattle relative to buffaloes, which was 2.237. Likelihood ratio tests
      showed a significant drop of the -2LL from univariable LR to multivariable LR
      models. Conclusion: There was an evidence of high seroprevalence of BVDV among
      cattle as compared with buffaloes with the possibility of infection in different
      age groups of animals. In addition, multivariable LR model was proved to provide
      more information for association and prediction purposes relative to univariable
      LR models and Chi-square tests if we have more than one predictor.

PMID- 29657415
TI  - Semi-nested polymerase chain reaction-based detection of Babesia spp. in small
      ruminants from Northwest of Iran.
AB  - Aim: The present study aimed to detect Babesia ovis and Babesia motasi in the
      blood samples of sheep and goats from Northwest of Iran by the semi-nested
      polymerase chain reaction (PCR) technique. Materials and Methods: A total of 166
      whole blood samples (including 123 sheep and 43 goats) were collected. In the
      first stage, the PCR was performed to amplify a piece of 18S rRNA gene of Babesia
      and Theileria genera. Then, semi-nested PCR was carried out on all PCR products
      to differentiate B. ovis and B. motasi. Results: The PCR indicated that totally,
      19 (11.44%) out of 166 samples were positive for Babesia or Theileria spp. The
      semi-nested PCR showed that 38 samples (22.89%) were positive only for B. ovis.
      No significant association was found between the infection rate of B. ovis and
      age, gender and species of animals. Conclusion: In the present study, there was
      no evidence for B. motasi infection in small ruminants from Northwest of Iran.
      Therefore, B. ovis was the main causative agent of ovine Babesiosis in this
      region.

PMID- 29657416
TI  - Prevailing practices in the use of antibiotics by dairy farmers in Eastern
      Haryana region of India.
AB  - Aim: The aim of the study was to assess the antibiotic use in dairy animals and
      to trace its usage pattern among the small, medium, and large dairy farmers in
      Eastern Haryana region of India. Materials and Methods: Karnal and Kurukshetra
      districts from Eastern region of Haryana state were purposively selected, and
      four villages from each district were selected randomly. From each village, 21
      farmers were selected using stratified random sampling by categorizing into
      small, medium, and large farmers constituting a total of 168 farmers as
      respondents. An antibiotic usage index (AUI) was developed to assess usage of
      antibiotics by dairy farmers. Results: Frequency of veterinary consultancy was
      high among large dairy farmers, and they mostly preferred veterinarians over para
      veterinarians for treatment of dairy animals. Small farmers demanded low-cost
      antibiotics from veterinarians whereas large farmers rarely went for it.
      Antibiotics were used maximum for therapeutic purposes by all categories of
      farmers. Completion of treatment schedules and follow-up were strictly practiced
      by the majority of large farmers. AUI revealed that large farmers were more
      consistent on decision-making about prudent use of antibiotics. Routine use of
      antibiotics after parturition to prevent disease and sale of milk without
      adhering to withdrawal period was responsible for aggravating the antibiotic
      resistance. The extent of antibiotic use by small farmers depended on the
      severity of disease. The large farmers opted for the prophylactic use of
      antibiotics at the herd level. Conclusion: Antibiotic usage practices were
      judicious among large dairy farmers, moderately prudent by medium dairy farmers
      and faulty by small farmers. The frequency of veterinary consultancy promoted
      better veterinary-client relationship among large farmers.

PMID- 29657417
TI  - Prevalence of American foulbrood in asymptomatic apiaries of Kurdistan, Iran.
AB  - Aim: Paenibacillus larvae subsp. larvae is the etiological agent of American
      foulbrood (AFB), the most virulent bacterial disease of honey bee brood
      worldwide. In many countries, AFB is a notifiable disease since it is highly
      contagious, in most cases incurable, and able to kill affected colonies. The aim
      of this study was to determine the prevalence of P. larvae subsp. larvae in
      Kurdistan province apiaries by polymerase chain reaction (PCR) technique.
      Materials and Methods: A total of 100 samples were randomly purchased from
      apiaries in Kurdistan, Iran. Apiaries were randomly sampled in accordance with
      the instructions of the veterinary organization from different provinces and were
      tested using PCR method and an exclusive primer of 16S rRNA for the presence of
      P. larvae subsp. larvae. Results: The results of this study indicated a low level
      of contamination with P. larvae subsp. larvae in the Kurdistan province. The
      number of positive samples obtained by PCR was 2%. Conclusion: Therefore,
      monitoring programs for this honeybee disease in Kurdistan should be developed
      and implemented to ensure that it is detected early and managed.

PMID- 29657418
TI  - Androctonus genus species in arid regions: Ecological niche models, geographical
      distributions, and envenomation risk.
AB  - Aim: The objective of this study was to establish environmental factors related
      to scorpion species occurrence and their current potential geographic
      distributions in Morocco, to produce a current envenomation risk map and also to
      assess the human population at risk of envenomation. Materials and Methods: In
      this study, 71 georeferenced points for all scorpion species and nine
      environmental indicators were used to generate species distribution models in
      Maxent (maximum entropy modeling of species geographic distributions) version
      3.3.3k. The models were evaluated by the area under the curve (AUC), using the
      omission error and the binomial probability. With the data generated by Maxent,
      distribution and envenomation risk maps were produced using the "ESRI(r) ArcGIS
      10.2.2 for Desktop" software. Results: The models had high predictive success
      (AUC >0.95+/-0.025). Altitude, slope and five bioclimatic attributes were found
      to play a significant role in determining Androctonus scorpion species
      distribution. Ecological niche models (ENMs) showed high concordance with the
      known distribution of the species. Produced risk map identified broad risk areas
      for Androctonus scorpion envenomation, extending along Marrakech-Tensift-Al
      Haouz, Souss-Massa-Draa, and some areas of Doukkala-Abda and Oriental regions.
      Conclusion: Considering these findings ENMs could be useful to afford important
      information on distributions of medically important scorpion species as well as
      producing scorpion envenomation risk maps.

PMID- 29657419
TI  - Giardiasis: Serum antibodies and coproantigens in brown rats (Rattus norvegicus)
      from Grenada, West Indies.
AB  - Aim: Giardia is a serious zoonotic parasite, which causes diarrheal disease in
      humans and animals including rodents. The purpose of this study was to estimate
      the prevalence of Giardia spp. in brown rats (Rattus norvegicus) in Grenada.
      Materials and Methods: Intestinal contents from 99 and serum samples from 169
      brown rats (R. norvegicus) from Grenada were collected. These samples were
      examined for the Giardia coproantigens using Cryptosporidium/Giardia Quik Chek
      assay (Tech lab(r) Inc., USA), and the serum was screened through an enzyme
      linked immunosorbent assay (ELISA) test kit for Giardia antibody (anti-GD) ELISA
      kit (MyBioSource, San Diego, CA, USA). Result: Giardia coproantigens were
      positive in 17.17% (95% confidence interval [CI]; 10.33-26.06%) rats, whereas 55%
      (95% CI: 47.20-62.68) were positive with serum antibodies (anti-GD) to Giardia.
      Conclusion: The prevalence of Giardia spp. in brown rats in Grenada was moderate
      based on the presence of coproantigens in the intestinal contents and antibody in
      serum. The findings of Giardia infections and prevalence in brown rats will help
      veterinarians and physicians to better plan diagnostic and preventative
      strategies. This is the first report of prevalence of Giardia in brown rats in
      Grenada.

PMID- 29657420
TI  - Meta-analysis of classical swine fever prevalence in pigs in India: A 5-year
      study.
AB  - Aim: The aim of the study was to determine the overall prevalence of classical
      swine fever (CSF) in pigs in India, through a systematic review and meta-analysis
      of published data. Materials and Methods: Consortium for e-Resources in
      Agriculture, India, Google Scholar, PubMed, annual reports of All India
      Coordinated Research Project on Animal Disease Monitoring and Surveillance, and
      All India Animal Disease database of NIVEDI (NADRES) were used for searching and
      retrieval of CSF prevalence data (seroprevalence, virus antigen, and virus
      nucleic acid detection) in India using a search strategy combining keywords and
      related database-specific subject terms from January 2011 to December 2015 in
      English only. Results: A total of 22 data reports containing 6,158 samples size
      from 18 states of India were used for the quantitative synthesis, and overall 37%
      (95% confidence interval [CI]=0.24, 0.51) CSF prevalence in India was estimated.
      The data were classified into 4 different geographical zones of the country: 20%
      (95% CI=0.05, 0.55), 31% (95% CI=0.18, 0.47), 55% (95% CI=0.32, 0.76), and 34%
      (95% CI=0.14, 0.62). CSF prevalence was estimated in northern, eastern, western,
      and southern regions, respectively. Conclusion: This study indicates that overall
      prevalence of CSF in India is much lower than individual published reports.

PMID- 29657421
TI  - Expression of vascular endothelial growth factor and matrix metalloproteinase-9
      in Apis mellifera Lawang propolis extract gel-treated traumatic ulcers in
      diabetic rats.
AB  - Aim: The aim of this study was to determine the effect of Apis mellifera propolis
      extract gel on vascular endothelial growth factor (VEGF) and matrix
      metalloproteinase-9 (MMP-9) expression in the traumatic ulcers of rats afflicted
      with diabetes mellitus (DM). Materials and Methods: The study was conducted on 24
      male Wistar rats (Rattus norvegicus) induced with DM by injecting 50 mg/kg of
      Streptozotocin, intraperitoneally, and a traumatic ulcer on their lower lip
      mucosa. These were divided into eight groups: Four each for control and treatment
      groups. Each control and treatment group consisted of three rats. The control
      groups treated with hydroxypropyl methylcellulose 5% gel and treatment groups
      were administered with propolis extract gel. The expression of VEGF and MMP-9 was
      observed on days 3, 5, 7, and 9. Furthermore, mice sacrificed and the lower lip
      labial mucosa tissue of mice has been taken to make the histopathology anatomy
      preparation by means of immunohistochemical examination with monoclonal
      antibodies anti-VEGF and anti-MMP-9. Results: This experiment revealed higher
      VEGF expression and lower MMP-9 expression in the treatment group as compared to
      that of the control group. Analysis of Variance showed significant differences
      (p<0.01) of both VEGF expression and MMP-9 expression between the two groups. A
      Tukey's analysis did not find strong contrasts in VEGF and MMP-9 expressions
      between various treatment groups. However, those between treatment and control
      groups were found to be considerable. Conclusion: Propolis extract gel increased
      the expression of VEGF and decreased that of MMP-9 during the healing process of
      traumatic ulcers on the oral mucosa of diabetes afflicted Wistar rats (R.
      norvegicus).

PMID- 29657422
TI  - Three Strigeid cercariae from Littorina littorea snail, Qarun Lake, Fayoum,
      Egypt.
AB  - Aim: The present study aims to focus on the role of common marine snails
      (Littorina littorea) as a vector for some trematode parasites. Materials and
      Methods: A total of 327 marine water L. littorea snails were collected during the
      summer of 2016 from a Qarun lake in the EL-Fayoum Governorate, Egypt. The snails
      were investigated for infection by trematode parthenitae through induction of
      cercarial shedding by exposure to light and crushing the snails. The species were
      stored in Search Laboratory of Zoology Department, Faculty of Science, Fayoum
      University. Results: Three species of Strigeid littorina cercaria were identified
      from the infected snails. They are described here and they identified in relation
      to close-up morphological features and linked to its snail hosts. They give the
      following names: Cercaria strigeid littorina type 1, C. strigeid littorina type
      2, and C. strigeid littorina type 3. The incidence of infection by these
      cercariae was 33%, 25.7%, and 2.4%, respectively. Conclusion: This study is
      clarifying the importance of this marine snail as intermediate hosts for new
      trematode species.

PMID- 29657423
TI  - Prevalence and characterization of Panton-Valentine leukocidin-positive
      Staphylococcus aureus in bovine milk in Jabalpur district of Madhya Pradesh,
      India.
AB  - Aim: The study aimed to investigate the Panton-Valentine leukocidin (PVL)
      positive Staphylococcus aureus in bovine milk due to its public health
      significance. Materials and Methods: A total of 400 milk samples of bovines taken
      from different dairy farms and outlets of Jabalpur were screened for the S.
      aureus and methicillin-resistant S. aureus (MRSA). The strains were tested for
      the PVL gene and antimicrobial sensitivity toward 10 different classes of
      antimicrobial agents. The PVL-positive S. aureus strains were further
      characterized by staphylococcal protein A or spa typing. Result: The prevalence
      of PVL-positive S. aureus was 10.53%. All the isolates positive for the PVL were
      resistant to methicillin, while the methicillin-sensitive S. aureus isolates were
      negative for the PVL. Five different spa types were found. Conclusion: The
      presence of PVL-positive MRSA in bovine milk close to consumer poses a potential
      public health risk to the community.

PMID- 29657424
TI  - The activity of pomegranate extract standardized 40% ellagic acid during the
      healing process of incision wounds in albino rats (Rattus norvegicus).
AB  - Aim: This research aimed to evaluate the effects of pomegranate extract
      standardized to 40% ellagic acid on the incised wound in albino rats. Materials
      and Methods: Fifty albino rats were divided into 10 treatment groups. The five
      groups were sacrificed on the 8th day, while the others were sacrificed on the
      15th day. Two groups of albino rats with incised wound were not treated at all
      (P0), the other two groups of albino rats with incised wound were treated with
      Betadine(r) (P1) ointment, and the rest of the groups were treated with
      pomegranate extract standardized to 40% ellagic acid with a concentration of 2.5%
      (P2), 5% (P3), and 7.5% (P4). The treatments were carried out twice a day with an
      interval of 12 h for 7 and 14 days. At the end of the research, the skin tissue
      of those albino rats had been taken for histopathologic preparations before H and
      E staining was performed. Results: Collagen deposition, polymorphonuclear
      neutrophils (PMN) infiltration, angiogenesis, and fibrosis degree in Group P4
      treated with 7.5% pomegranate extract standardized to 40% ellagic acid for 14
      days were significantly different from those in Groups P0, P1, P2, and P3,
      especially in the case of PMN inflammation (p<0.05). Conclusion: The
      administration of 7.5% pomegranate extract standardized to 40% ellagic acid for
      14 days on incised wounds of those albino rats can accelerate the wound healing
      process characterized by collagen deposition improvement, PMN infiltration in the
      wound area, angiogenesis, and fibrosis degree.

PMID- 29657425
TI  - Serum cortisol level and survival rate of juvenile Epinephelus fuscoguttatus
      following exposure to different salinities.
AB  - Background and Aim: Brown-marbled grouper Epinephelus fuscoguttatus is a premium
      marine food fish with high demand in Asia. In fish, stress due to environmental
      changes such as fluctuations in the salinity can result in increased cortisol
      level. Stress in fish increases susceptibility to diseases ultimately resulting
      in death. Therefore, the aim of this study was to investigate the salinity
      tolerance of E. fuscoguttatus and their survival in lower salinities. Materials
      and Methods: In this study, grouper juveniles (92.43+/-standard error of the mean
      0.51 mm) maintained in 31 ppt seawater were transferred into five tanks with
      seawater diluted to 25, 20, 15, 10, and 5 ppt. The salinity of the control group
      was not changed and was maintained at 31 ppt. Serum cortisol was measured using
      ELISA at 0, 30, 60, and 120 min after the fish were transferred to the different
      concentrations of salinity. Results: The survival percentage was recorded for 14
      days following the transfer and the results revealed that serum cortisol of fish
      in a high change in salinity (15, 10, and 5 ppt) was significantly higher than
      the control group immediately after exposure. At the high salinity change, the
      cortisol levels gradually decrease at 30 min and 60 min, until no difference in
      cortisol concentration was observed at 120 min. No mortality was observed in fish
      exposed to low salinity change (25 and 20 ppt) while in higher salinity change (5
      ppt), the survival percentage was 50%. Conclusion: The study revealed that the
      serum cortisol concentration was high initially and continues to decrease to
      resting cortisol level at 120 min indicating that cortisol hormone is released
      following acute stress as a primary response in grouper juveniles.

PMID- 29657426
TI  - Status of theileriosis among herbivores in Iran: A systematic review and meta
      analysis.
AB  - Aim: Theileriosis is a protozoal disease caused by Theileria spp. mostly in warm
      blooded vertebrates worldwide. It is one of the common tick-borne diseases among
      domestic animals in tropical and sub-tropical regions, which have a variety of
      unlikable effects on health economy and animal welfare. In the present study, the
      prevalence of theileriosis among domestic farm animals in Iran was systematically
      evaluated. Methods: To identify the related papers, 10 English and Persian
      databases, including PubMed, Science Direct, Scopus, Web of Science, Medical
      Subject Headings, Google Scholar, Magiran, Barakatns (formerly Iranmedex), Elm
      net, and Scientific Information Database, were appraised for articles published
      throughout 1999-2017. Results: A total of 56 papers, providing the examination of
      11,317 cattle, 9394 sheep, 2991 buffaloes, 1504 horses, 600 goats, and 212
      donkeys were analyzed, matching for the prevalence of theileriosis from different
      parts of Iran were permitted for our allowing checklist. The overall prevalence
      of theileriosis among domestic herbivores was expected to be 19% (95% confidence
      interval: 15%, 22%). Our findings highlighted the average of the maximum
      prevalence in Razavi Khorasan (60.4%) and West Azerbaijan (49.1%) and the minimum
      in Mazandaran (1.1%) and East Azerbaijan provinces (2.2%), respectively. The high
      prevalence of Theileria infection in the herbivores (mainly sheep) verifies the
      well-known enzootic episode of theileriosis in Iran, predominantly in
      northeastern and western parts of the country. Conclusion: Our results suggested
      updated and imperative information on the true burden of theileriosis in Iran.
      Moreover, it could be supporting the gaps among monitoring, prevention, and
      control arrangements to improve the health economy, particularly among dairy farm
      animals.

PMID- 29657427
TI  - Antibacterial activity of fig leaf (Ficus carica Linn.) extract against
      Enterococcus faecalis and its cytotoxicity effects on fibroblast cells.
AB  - Background: Enterococcus faecalis is one of the bacteria that commonly found in
      root canal and pulp infection after root canal treatment. Sodium hypochlorite is
      the most widely used root canal irrigation, but it has toxic properties if
      exposed to periradicular tissues. It is necessary to develop an alternative for
      root canal irrigation. Fig leaf (Ficus carica Linn.) extract contains active
      substances such as flavonoid, tannin, and terpenoid which have been known for
      their antibacterial potency. Aim: This study aimed to determine the minimum
      bactericidal concentration (MBC) of fig leaf (F. carica Linn.) extract against E.
      faecalis and its cytotoxicity on fibroblast cells in vitro. Materials and
      Methods: A serial dilution method was used to determine the MBC of fig leaf
      extract on E. faecalis which grown on nutrient agar media. Inoculation was
      carried out at concentrations that suspected minimum inhibitory concentration
      (MIC), MBC, concentration between MIC and MBC, and control groups on different
      nutrient agar. MIC and MBC of fig leaf extract against E. faecalis were known by
      counting the growth of bacteria colonies on nutrient agar media in CFU/ml. The
      cytotoxicity of MIC and MBC of the extract acquired were tested using 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and the results were
      read using an ELISA reader. Data of E. faecalis colonies were analyzed using
      Kruskal-Wallis and Mann-Whitney test. Results: The result showed a significant
      difference among the groups (p<0.05). fig leaf extract at a concentration of 50%
      showed no bacterial growth, and cell viability at this concentration was 77.7%.
      Conclusion: Fig leaf extract has antibacterial effect on E. faecalis with MBC at
      50% and not cytotoxic to fibroblast cells.

PMID- 29657428
TI  - Virulence gene profiling of porcine Pasteurella multocida isolates of Assam.
AB  - Aim: The present study was conducted to detect and identify the virulence genes
      in Pasteurella multocida isolates of porcine origin from Assam. Materials and
      Methods: A total of 21 porcine P. multocida isolates were subjected to capsular
      typing and detection of virulence-associated genes (pfhA, tbpA, hgbB, toxA,
      oma87, ompH, and nanB) using various polymerase chain reaction (PCR) methods
      reported elsewhere. Further, pathogenicity of the porcine isolates of P.
      multocida was studied in mice. For each strain of P. multocida selected for
      pathogenicity trial, the group of mice was injected intraperitoneally (i/p) with
      0.1 ml of the inoculum prepared from respective field isolates, containing 109
      organisms per ml. Results: Capsular typing of the isolates by multiplex PCR
      showed two capsular types, type A (66.66%) and type D (33.33%). All the isolates
      were positive for outer membrane protein genes, oma87 and ompH genes. Iron
      acquisition genes, tbpA and hgbB, were detected in 14.28% and 19.04% of the
      isolates. The dermonecrotoxin encoding gene, toxA, was present in 23.80% of the
      isolates. Filamentous hemagglutinin encoding gene, pfhA, was detected in 28.57%.
      The virulence gene distribution pattern of the isolates indicates the important
      role of the genes in disease pathogenesis. Conclusion: From the present study, it
      can be concluded that toxA gene is an important marker gene for defining the
      pathogenic potential of P. multocida strains in swine.

PMID- 29657429
TI  - Isolation and identification of bacteria causing mastitis in small ruminants and
      their susceptibility to antibiotics, honey, essential oils, and plant extracts.
AB  - Aim: The present work aims to isolate and identify bacteria that cause mastitis
      in small ruminants and evaluates the antibacterial activity of some antibiotics,
      honey, essential oils, and plant extracts. Materials and Methods: A total of 289
      milk samples were collected from udder secretions of sheep (n=189) and goat
      (n=100) from El-Fayoum, Beni-Suef, and Giza governorates. Screening subclinical
      mastitis (SCM) was done using California Mastitis Test (CMT); identification of
      the isolates was achieved using Gram's staining, hemolytic pattern, colony
      morphology, and biochemical tests using Analytical Profile Index. Results: On
      clinical examination, the incidence of clinical mastitis (CM) was found to be
      5.88% and 7% in sheep and goat, respectively. On CMT, SCM was found to be 25
      (13.23%) and 11 (10%) in sheep and goat, respectively. Bacteriological
      examination of all milk samples found the presence of Staphylococcus aureus (SA)
      (31.1%), coagulase-negative staphylococci (CNS) (19.5%), Escherichia coli (EC)
      (8.3%), Streptococcus spp. (5.6%), Klebsiella spp. (3.77%), and Pseudomonas spp.
      (1.89%), while no bacteria were cultured from 81.66% of the samples.
      Identification of 9 isolates of CNS was achieved by using API staph test to
      Staphylococcus epidermidis, Staphylococcus hominis, Staphylococcus cohnii, and
      Staphylococcus saprophyticus. The highest bacterial resistance was found in EC
      (67.14%) followed by Kp (45.28%) and SA (26.57%). Conclusion: Onion and black
      cumin essential oils followed by Egyptian honey showed strong antibacterial
      effects against multidrug-resistant bacteria. Finally, our study proved that
      Egyptian honey, onion, and black cumin essential oils have a marked strong
      antibacterial effect against bacteria isolated from small ruminant mastitis, but
      still further extensive studies are needed to discover the therapeutic properties
      of these plant extracts and honey.

PMID- 29657430
TI  - Detection of Brucella spp. in milk from seronegative cows by real-time polymerase
      chain reaction in the region of Batna, Algeria.
AB  - Aim: The aim of this study was to detect Brucella spp. DNA in milk samples
      collected from seronegative cows using the real-time polymerase chain reaction
      (PCR) assay for diagnosis of brucellosis in seronegative dairy cows to prevent
      transmission of disease to humans and to reduce economic losses in animal
      production. Materials and Methods: In this study, 65 milk samples were
      investigated for the detection of Brucella spp. The detection of the IS711 gene
      in all samples was done by real-time PCR assay by comparative cycle threshold
      method. Results: The results show that of the 65 DNA samples tested, 2 (3.08%)
      were positive for Brucella infection. The mean cyclic threshold values of IS711
      real-time PCR test were 37.97 and 40.48, indicating a positive reaction.
      Conclusion: The results of the present study indicated that the real-time PCR
      appears to offer several advantages over serological tests. For this reason, the
      real-time PCR should be validated on representative numbers of Brucella-infected
      and free samples before being implemented in routine diagnosis in human and
      animal brucellosis for controlling this disease.

PMID- 29657431
TI  - Evaluation of antimycobacterial activity of Curcuma xanthorrhiza ethanolic
      extract against Mycobacterium tuberculosis H37Rv in vitro.
AB  - Aim: The aim of this study was to evaluate the antimycobacterial activity of the
      Curcuma xanthorrhiza ethanolic extract in vitro. Materials and Methods: Ethanolic
      extract of C. xanthorrhiza was set by maceration method. The broth microdilution
      and disc diffusion method were used to determine the minimal inhibitory
      concentration (MIC) and minimal bactericidal concentration (MBC), respectively,
      of C. xanthorrhiza ethanol extract on strain Mycobacterium tuberculosis H37Rv.
      Results: C. xanthorrhiza ethanol extract was found to have the antimycobacterial
      effects with a MIC value of 1600 MUg/ml while MBC value of 3200 MUg/ml for M.
      tuberculosis H37Rv. Conclusion: From these findings , it can be concluded that C.
      xanthorrhiza ethanol extract have an antibacterial activity against Mycobacterium
      tuberculosis H37Rv in vitro and its potency elevated by increasing the C.
      xanthorrhiza ethanol extract concentration.

PMID- 29657432
TI  - Antibacterial and antioxidant activity of Juniperus thurifera L. leaf extracts
      growing in East of Algeria.
AB  - Aim: This work aimed to evaluate the biological activity of the leaf extracts of
      Juniperus thurifera L., which is an Algerian endemic tree that belongs to the
      family of Cupressaceae. Materials and Methods: The plant leaves were extracted in
      solvents of increasing polarity to obtain different extracts such as methanol,
      petroleum ether, chloroform, ethyl acetate, and aqueous extracts (MeE, PEE, ChlE,
      EtAE, and AqE). The antioxidant activity of four extracts (MeE, ChlE, EtAE, and
      AqE) was assessed by trapping test of 1,1-diphenyl-2-picrylhydrazyl (DPPH)
      radical. The evaluation of antibacterial activity of MeE, ChlE, EtAE, and PEE was
      done using the disk diffusion method on solid agar. Results: The three extracts
      of EtAE, AqE, and MeE showed high antiradical activity toward the DPPH radical
      (IC50=29.348 ug/mL, 37.538 ug/mL, and 52.573 ug/mL, respectively), while the
      lowest radical scavenging activity was expressed by the ChlE (IC50=70.096 ug/mL).
      These extracts were active only toward the Gram-positive bacteria (Staphylococcus
      aureus ATCC and methicillin-resistant S. aureus) at different concentrations, and
      the highest activity was obtained with the ChlE with an inhibition diameter of 14
      mm at the concentration of 1 g/mL. No inhibition was detected for all of these
      extracts against the Gram-negative tested strains (Escherichia coli ATCC,
      Pseudomonas aeruginosa ATCC, and Enterobacter cloacae (extended spectrum beta
      lactamase). Conclusion: From this study, on the one hand, it was concluded that
      J. thurifera L. leaves extracts exhibited a very intense antioxidant potential
      toward the DPPH radical, and on the other hand, the antibacterial activity showed
      an action spectrum exclusively toward the Gram-positive bacteria.

PMID- 29657433
TI  - Isolation of Shiga toxin-producing Escherichia coli harboring variant Shiga toxin
      genes from seafood.
AB  - Background and Aim: Shiga toxin-producing Escherichia coli (STEC) are important
      pathogens of global significance. STEC are responsible for numerous food-borne
      outbreaks worldwide and their presence in food is a potential health hazard. The
      objective of the present study was to determine the incidence of STEC in fresh
      seafood in Mumbai, India, and to characterize STEC with respect to their
      virulence determinants. Materials and Methods: A total of 368 E. coli were
      isolated from 39 fresh seafood samples (18 finfish and 21 shellfish) using
      culture-based methods. The isolates were screened by polymerase chain reaction
      (PCR) for the genes commonly associated with STEC. The variant Shiga toxin genes
      were confirmed by Southern blotting and hybridization followed by DNA sequencing.
      Results: One or more Shiga toxins genes were detected in 61 isolates. Of 39
      samples analyzed, 10 (25.64%) samples harbored STEC. Other virulence genes,
      namely, eaeA (coding for an intimin) and hlyA (hemolysin A) were detected in 43
      and 15 seafood isolates, respectively. The variant stx1 genes from 6 isolates
      were sequenced, five of which were found to be stx1d variants, while one sequence
      varied considerably from known stx1 sequences. Southern hybridization and DNA
      sequence analysis suggested putative Shiga toxin variant genes (stx2) in at least
      3 other isolates. Conclusion: The results of this study showed the occurrence of
      STEC in seafood harboring one or more Shiga toxin genes. The detection of STEC by
      PCR may be hampered due to the presence of variant genes such as the stx1d in
      STEC. This is the first report of stx1d gene in STEC isolated from Indian
      seafood.

PMID- 29657434
TI  - Inventory of lice of mammals and farmyard chicken in North-eastern Algeria.
AB  - Background and Aim: Lice are permanent ectoparasites, extremely specific to their
      hosts. Their great importance in veterinary medicine remain significant, they can
      cause their direct pathogenic actions like irritability, dermatitis, anemia,
      decreased weight gain, and milk production. The purpose of this work was to made
      the first time an inventory of mammalian lice in North-eastern Algeria. Materials
      and Methods: Our survey of lice infestation was conducted on several animal
      species from five provinces of North-eastern Algeria. A total of 57 cattle, 83
      sheep, 77 goats, 111 wild boars, and 63 farmyard chickens were examined. The
      collection of lice was carried out much more in mammals and chickens during the
      winter period. Lice were collected either manually or using brushing and kept in
      flasks containing 70% ethanol. The identification of lice was achieved in the
      laboratory using a binocular loupe. Results: Concerning cattle, 63% and 27% of
      those examined subjects from Souk-Ahras and Guelma study areas, respectively,
      were carriers of lice. Damalinia bovis was the louse most frequently found on
      cattle in these two regions. Three other species were identified in Souk-Ahras:
      Haematopinus eurysternus (25%), Linognathus vituli (10%), and Solenopotes
      capillatus (5%). Regarding sheep, 39% and 24% of examined animals in Souk-Ahras
      and Guelma, were carrying lice. Damalinia ovis was the most frequently
      encountered lice on sheep in both regions. Linognathus ovillus also was
      identified in Souk-Ahras, representing 0.3% of the collected lice. Concerning
      goats, 53% and 30% of examined animals in Souk-Ahras and Guelma, were parasitized
      of lice. Two species of lice were found: Damalinia caprae and Linognathus
      africanus. For farmyard chickens, 69% and 100% of the farmyard chicken in Souk
      Ahras and Mila were parasitized by lice, respectively. Menopon gallinae was the
      most frequently encountered louse in farmyard chicken in both regions. Eight
      other species were identified in Mila and four other species only in Souk-Ahras.
      Finally, 25% and 28% of the wild boars in Annaba and El Tarf were parasitized by
      lice, respectively. Haematopinus suis was the only species found on wild boars in
      both regions. Conclusion: These results are to be taken into account for lice
      control schemes and louse-borne diseases.

PMID- 29657435
TI  - ISMap02 element targeted nested polymerase chain in the detection of
      Mycobacterium avium subsp. paratuberculosis in fecal samples of cattle and
      buffaloes.
AB  - Background and Aim: Johne's disease is chronic granulomatous enteritis which
      affects ruminants. There are many diagnostic approaches for the detection of
      Mycobacterium avium subsp. paratuberculosis (MAP) of which molecular detection
      methods using various elements are less time consuming and more accurate. The
      present study was conducted using ISMap02 element for nested polymerase chain
      reaction (nPCR) based detection of MAP in fecal samples. The aim was to test the
      sensitivity and specificity of the ISMap02 element and also to use this element
      for the detection of MAP in fecal samples of cattle and buffaloes. Materials and
      Methods: A total of 211 fecal samples of cattle and buffaloes from different
      herds around Ludhiana aged between 2 and 13 years were collected, and DNA
      extraction was done from these samples. The nPCR was carried out for the
      detection of MAP in fecal samples. Results: The ISMap02 element was specific for
      the detection of MAP only and showed a sensitivity of detection of 7.6 fg/uL of
      the standard genomic DNA. Among the 211 fecal samples of cattle and buffaloes
      tested for the ISMap02 element, 18 samples (8.5%) were positive for MAP.
      Conclusion: The ISMap02 element is specific and sensitive for the detection of
      MAP in various samples, and when used in nPCR format, it can increase the
      sensitivity of detection.

PMID- 29657437
TI  - Clinical and radiological outcome for Trufit Plug in the treatment of chondral
      and osteochondral lesions at a minimum of 2 years.
AB  - The aim of this study was to evaluate the functional and radiological outcome of
      TruFit plugs. We retrospectively reviewed 10 patients who underwent treatment for
      a symptomatic chondral/osteochondral lesion using one or more Trufit Plugs. Full
      incorporation of the bony portion of the plug occurred in only 3 and partial
      incorporation in 7 lesions. The remaining portion of these 7 lesions looked
      cystic on MRI. The significance of this cystic change is not clear. Though all 10
      patients showed some improvement on the IKDC scoring system but the amount of the
      improvement was small.

PMID- 29657436
TI  - Upper extremity weightlifting injuries: Diagnosis and management.
AB  - Common upper extremity injuries in resistance training athletes include muscle
      strains, ligament sprains, pectoralis major tendon ruptures, distal biceps tendon
      ruptures, and chronic shoulder pain and capsulolabral injuries. While each injury
      is unique in its specific anatomic location and mechanism, each is preventable
      with proper exercise technique, safety and maintenance of muscle balance.
      Conservative treatment is the therapeutic modality of choice and these injuries
      generally resolve with workout modification, appropriate recovery, anti
      inflammatory medication, and physical therapy. If conservative treatment fails,
      surgical intervention is often successful and can return the weightlifter to a
      level of performance near their pre-injury level.

PMID- 29657438
TI  - Red blood cell distribution width (RDW) and its potential significance to
      orthopedic surgeons.

PMID- 29657439
TI  - Topical vancomycin and its effect on survival and migration of osteoblasts,
      fibroblasts, and myoblasts: An in vitro study.
AB  - The purpose of this study was to examine the influence of topical vancomycin on
      cell migration and survival of tissue healing cells. Human osteoblasts, myoblasts
      and fibroblasts were exposed to vancomycin at concentrations of 1, 3, 6, or 12
      mg/cm2 for either a 1-h or 48-h (continuous) duration. Continuous exposure to all
      vancomycin concentrations significantly reduced cell survival (<22% cells
      survived) and migration in osteoblasts and myoblasts (P < 0.001). 1-h vancomycin
      exposure reduced osteoblast and myoblast survival and migration only at 12 mg/cm2
      (P < 0.001). Further in vivo studies are warranted to optimize the dosage of
      intrawound vancomycin.

PMID- 29657440
TI  - Magnetic growth modulation in orthopaedic and spine surgery.
AB  - Purpose: To examine distraction-based methods for treatment of early onset
      scoliosis (EOS), focusing on the magnetically controlled growing rod system
      (MCGR) relative to traditional growing rod system (TGR). To briefly discuss
      internal magnetically controlled nails for bone lengthening as another
      application of magnetic growth modulation. Results: Relative to TGR, MCGR
      involves fewer complications related to infection and general anesthesia because
      of fewer successive surgeries required. Further, MCGR accounts for better
      psychosocial patient outcome and potentially a lower long-term cost, mainly
      because of shortened periods of hospitalization. Intramedullary lengthening nails
      involve fewer complications compared to internal limb lengthening devices related
      to infections, nerve damage, shortening, improper healing, stiffness, and
      scarring. Intramedullary lengthening nails appear to alleviate psychosocial
      burden of patients especially when compared to external fixators. Conclusions:
      Although the current gold standard for treating some types of early onset
      scoliosis (EOS) is the traditional growing rod system, the magnetically
      controlled growing rod (MCGR) system is an alternative method for treating EOS.
      MCGR is promising in that it involves less surgical procedures, shorter hospital
      stays, and lower long-term cost relative to TGR. Similarly, the use of
      magnetically controlled intramedullary lengthening nails is a promising
      alternative to the Ilizarov method for limb lengthening.

PMID- 29657441
TI  - Percutaneous upper extremity fracture fixation using a novel glass-based
      adhesive.
AB  - Objective: To develop a surgical technique for percutaneous upper extremity
      fracture fixation using a novel glass-based adhesive. Methods: Three intact upper
      extremity cadaveric specimens with undisturbed soft tissues were obtained. Two
      were used to model a wrist fracture, and the third to model a proximal humerus
      fracture. Fractures were produced using a small osteotome in a percutaneous
      fashion. Banna Bone Adhesive (BBA) was delivered to the fracture site
      percutaneously using a 16 gauge needle under bi-planar fluoroscopic guidance.
      After setting of the adhesive, the specimens were dissected to qualitatively
      assess BBA delivery and placement. Results: The adhesive could readily be
      delivered through the 16 gauge needle with an appropriate amount of pressure
      applied to the syringe. Using the fluoroscope, the adhesive could be seen to flow
      into the fracture site with minimal extravagation into the surrounding soft
      tissues. Successful bonding of the fracture fragments was observed. Conclusions:
      Percutaneous delivery of BBA into a fracture of the distal radius and proximal
      humerus may be a feasible fracture fixation technique. Biomechanical testing and
      animal model testing are required to further develop this procedure.

PMID- 29657442
TI  - Obesity is associated with higher complication rates in revision total hip
      arthroplasty.
AB  - We examined differences in complication rates between obese and non-obese
      patients undergoing revision total hip arthroplasty. Sixty-five patients with a
      BMI >=30 kg/m2 and 54 patients with a BMI of <30 kg/m2 were identified. Obese
      patients were 2.5 times more likely to suffer a complication than non-obese
      (38.4% cf 14.8%, p = 0.02). Obese patients were more likely to experience
      dislocation, leg length discrepancy, fracture, implant loosening, infection and
      pulmonary embolus. The obese group had a significantly higher revision rate
      (12.3% cf 1.8%, p = 0.039). Obese patients should be counselled pre-operatively
      on their elevated risk.

PMID- 29657443
TI  - Healing of femoral fractures by the meaning of an innovative intramedullary nail.
AB  - In this paper, an innovative design of nail, conceived to heal fractures of long
      bones has been investigated. Its functioning is based essentially on sliding of
      conical surfaces located in a spindle and in a series of holding pins radially
      disposed around it. Spindle and holding pins are connected together by means of a
      sleeve. Medial and distal screws are not necessary. Rotational and longitudinal
      motions of the spindle are transformed in a radial expansion of the holding pins
      by the sliding of conical surfaces. A complete numerical FE model of an implanted
      femur was realized and analyzed by the mean of two loading configurations: LC1 by
      imposing a vertical load of 980 N, and LC2 by considering resultants of the
      muscle actions. Analyses confirmed results, in terms of mechanical performances,
      comparable with the others traditional systems of prosthesis.

PMID- 29657444
TI  - Radial axial interosseous load (RAIL) test for essex lopresti type injuries.
AB  - Background: When approaching radial head and neck fractures, the decision for
      ORIF, resection, or arthroplasty is often performed intraoperatively. Factors
      that contribute include ligamentous and bony stability, cartilage injury,
      mechanical alignment as well as patient factors. Recent data has suggested
      conventional methods may not be sufficiently sensitive in detecting Essex
      Lopresti injuries. Here we describe an intraoperative technique that could
      objectively assess proximal radio-ulnar stability with subsequent disruption of
      the ligamentous structures. Methods: Eight cadaveric specimens were used to
      evaluate amount of radial proximal migration between three groups of forearms.
      After radial head resection, proximal migration of the radial shaft was measured
      in three distinct groups. Group A included intact forearms, Group B included
      forearms with resected interosseous membranes (IOM), and Group C included
      forearms with resected interosseous membranes and distal radioulnar joint (DRUJ)
      disruptions. Results: As compared to group A, group B averaged 4 mm of proximal
      radial migration (p < 0.01), while Group C demonstrated >6 mm of migration (p <
      0.01). Conclusion: In the setting of a non-repairable radial head, the RAIL test
      may provide a more objective means of assessing for Essex-Lopresti injuries.

PMID- 29657445
TI  - Tranexamic acid in total hip arthroplasty: Mixed treatment comparisons of
      randomized controlled trials and cohort studies.
AB  - Background: The present study is a network meta-analysis of various routes of
      tranexamic acid (TXA) in patients with total hip arthroplasty (THA). Methods:
      Randomized controlled trials and cohort studies evaluating TXA in patients with
      THA were included. Number of patients requiring blood transfusion was the primary
      outcome. Results: Pooled estimate for TXA use against placebo for blood
      transfusion rate was 0.30 [0.23, 0.39] favoring TXA. Maximum reduction in the
      risk of blood transfusion was observed with topical plus intra-operative
      intravenous TXA. Conclusion: Combined topical and intravenous TXA during surgery
      may perform better than other modes in patients undergoing THA.

PMID- 29657446
TI  - Assessment of the risk of low bone mineral density in premenopausal Japanese
      female patients with systemic lupus erythematosus.
AB  - Background: The aim of this study was to assess the relationships between
      clinical parameters and bone mineral density (BMD) in Japanese female patients
      with systemic lupus erythematosus (SLE). Methods: A total of female 136 SLE
      patients without menopause were retrospectively assessed to identify associations
      between age, disease duration, body mass index (BMI), glucocorticoid usage and
      disease activity and BMD based on the treatment with or without bisphosphonate.
      There were 71 patients treated with bisphosphonate (bisphosphonate group) and 65
      patients without (non-bisphosphonate group). We evaluated the impact of age,
      disease duration, BMI, serologic SLE markers, glucocorticoid use on BMD of the
      anterior-posterior (AP) and lateral lumbar spine, total hip and femoral neck
      using univariate and multivariate linear regression analyses of both
      bisphosphonate and non-bisphosphonate groups. Results: Multivariate linear
      regression analyses showed that in non-bisphosphonate group disease duration was
      negatively associated with BMD of AP spine and femoral neck, whereas in
      bisphosphonate group these negative associations were not present. However,
      multivariate linear regression analyses showed a significant relationship between
      BMI and BMD of the AP spine, femoral neck and total hip, regardless of
      bisphosphonate treatment. Conclusions: Bisphosphonate treatment eliminated the
      negative relationships between disease duration and the BMD of the spine and hip.
      AP spine and hip BMD in patients with SLE depend on BMI, regardless of
      bisphosphonate use. SLE serologic markers and glucocorticoid use were not
      negatively associated with generalized bone loss. SLE patients with low BMI have
      a high risk of generalized bone loss, and should be assessed and treated to
      prevent osteoporosis even before menopause.

PMID- 29657447
TI  - Evaluation of reproducibility of robotic knee testing device (GNRB) on 60 healthy
      knees.
AB  - Introduction: There is a main concern about the usefulness and the accuracy of
      the different laximeters. The GnrB device is becoming more popular, but according
      to the literature it's not clear whether it is fully reliable. Objective: GNRB
      laxity measurements are not reproducible for measurement of anterior translation
      of the tibia. Material and methods: We analyzed the reproducibility of GNRB
      measurements in healthy subjects by the Test-Retest method in 2 sessions.
      Results: 30 pairs of healthy knees were assessed. Test-Retest agreement was poor
      for both absolute values and for differentials at 134 and 200 N with an intra
      class correlation ranging from 0.210 to 0.486. There was a significant differance
      in anterior tibial translation, in side-to-side difference, according to the
      patellar pressure. Conclusion: The reproducibility is found to be poor under
      optimum conditions of comparability. The patellar pressure influences strongly
      thelaxity value.

PMID- 29657448
TI  - Diagnostic difficulties in the radiological assessment of subscapularis tears.
AB  - Background: Radiological evaluation of rotator cuff tears are sensitive and
      specific. Accuracy may be low in diagnosing subscapularis tears. Materials and
      methods: We retrospectively reviewed shoulder arthroscopies performed by two
      surgeons over 45 months. We reviewed patients who had subscapularis repairs and
      their preoperative imaging. Result: 286 cases had imaging (193 MRIs, 93 USS) with
      77 subscapularis repairs. MRI suggested 31 tears, arthroscopy confirmed 16 (30%
      sensitivity, 89% specificity). USS suggested 6 tears, arthroscopy confirmed 4
      (13% Sensitivity, 97% specificity). Discussion: Results demonstrated low accuracy
      for preoperative radiological subscapularis tear assessment. This has logistical,
      diagnostic and implications on treatment.

PMID- 29657449
TI  - Analysis of glenoid inter-anchor distance with an all-suture anchor system.
AB  - Background: All-suture anchors used in arthroscopic shoulder stabilization employ
      small diameter anchors, which allow greater placement density on narrow surfaces
      such as the glenoid. There is no consensus in the literature about how close to
      one another two anchors may be implanted. Purpose: The purpose of the present
      study is to compare the strength characteristics of two all-suture anchors placed
      in cadaveric human glenoid at variable distances to one another, in order to
      determine the minimum distance required for optimal strength. Methods: Twelve
      fresh-frozen human cadaveric glenoids were implanted with 1.4 mm all-suture
      anchors at varying inter-anchor distances. Each glenoid was used for four tests,
      for a total of 48 tests. Anchors were implanted adjacent to one another or with
      2, 3, or 5 mm bone bridges between pilot holes. The glenoids then underwent
      pullout testing using a test frame with a 5N preload followed by displacement of
      12.5 mm/s. The primary outcomes were stiffness, failure strength, and ultimate
      strength. Results: Stiffness was 13.52 +/- 3.8, 17.97 +/- 5.02, 17.59 +/- 4.65
      and 18.95 +/- 4.67 N/mm for the adjacent, 2, 3, and 5 mm treatment groups,
      respectively. The adjacent group had a significantly lower stiffness compared to
      the other treatment groups. Failure strength was 48.68 +/- 20.64, 76.16 +/-
      23.78, 73.19 +/- 35.83 and 87.04 +/- 34.67 N for the adjacent, 2, 3, and 5 mm
      treatment groups, respectively. The adjacent group had a significantly lower
      failure strength compared to the other treatment groups. Ultimate strength was
      also measured to be 190.59 +/- 140.93, 268.7 +/- 115.1, 283.23 +/- 118.43, and
      291.28 +/- 118.24 for the adjacent, 2, 3, and 5 mm treatment groups,
      respectively. Conclusions: This biomechanical study provides evidence that 1.4 mm
      all-suture anchors demonstrate similar strength characteristics when placed at
      least 2 mm or greater from one another. When 1.4 mm all-suture anchors were
      placed adjacent to one another, there was an observed decrease in failure
      strength and stiffness. Clinical relevance: This study suggests that 1.4 mm all
      suture anchors may be placed as close as 2 mm to one another while preserving
      strength characteristics.

PMID- 29657450
TI  - Current advances in the treatment of medial and lateral epicondylitis.
AB  - Despite advances elucidating the causes of lateral and medial epicondylitis, the
      standard of care remains conservative management with NSAIDs, physical therapy,
      bracing, and rest. Scar tissue formation provoked by conservative management
      creates a tendon lacking the biomechanical properties and mechanical strength of
      normal tendon. The following review analyzes novel therapies to regenerate tendon
      and regain function in patients with epicondylitis. These treatments include PRP
      injection, BMAC, collagen-producing cell injection, and stem cell treatments.
      While these treatments are in early stages of investigation, they may warrant
      further consideration based on prospects of pain alleviation, function
      enhancement, and improved healing.

PMID- 29657451
TI  - Total hip arthroplasty in Hurler syndrome - 8 years follow up - A case report
      with review of literature.
AB  - Life expectancy in Hurler syndrome is significantly improved by enzyme therapy
      with bone marrow transplantation. However, the deterioration of skeletal
      abnormalities persists. Hip dysplasia is a common presentation which may progress
      to significant hip arthritis requiring total hip arthroplasty at later stage. We
      report a long-term outcome of cementless total hip arthroplasty in a patient with
      Hurler syndrome who was successfully treated with bone marrow transplant.

PMID- 29657452
TI  - Impact of various foot arches on dynamic balance and speed performance in
      collegiate short distance runners: A cross-sectional comparative study.
AB  - Objective: To compare the impact of foot arches on dynamic balance and speed
      performance. Materials and methods: 30 collegiate male short distance runners
      were divided into three groups based on foot arches, high, neutral and low.
      Balance and speed performance were estimated based on scores of star excursion
      balance test (SEBT), 40 yard dash test and vertical jump test (VJT). Results:
      Significant improved scores (p < 0.001) were noted in SEBT, 40 yard dash test and
      VJT. Conclusion: Short distance runners with high arch foot have improved dynamic
      balance and speed when compared to low and neutral arch foot.

PMID- 29657453
TI  - Periprosthetic hip fractures: A review of the economic burden based on length of
      stay.
AB  - Introduction: With the increasing rates of total hip replacements being performed
      worldwide, there is an increasing incidence of periprosthetic fractures. As our
      patients' demographics change to include older patients with multiple medical co
      morbidities, there is a concurrent increase in morbidity and mortality rates.
      This leads to longer hospital stays and increasing hospital costs. In the current
      economic climate, the cost of treating periprosthetic fractures must be addressed
      and appropriate resource and funding allocation for future provision of services
      should be planned. Materials and methods: All periprosthetic hip fractures that
      were admitted to a single trauma unit over a three-year period were reviewed.
      Independent chart review, haematological and radiological review was undertaken.
      All patients with a periprosthetic fracture associated with a total hip
      arthroplasty or hemiarthroplasty were included. Follow up data including
      complications were collated. Data from the hospital inpatient database and
      finance department was utilized for cost analysis. All statistical analysis was
      preformed using Minitab version 17. Results: 48 patients were identified who met
      the inclusion criteria for review. The majority of participants were female with
      a mean age of 73.5 years. The mean time to fracture was 4.5 years (9 months-18.5
      years). Periprosthetic fracture was associated with total hip arthroplasty in 24
      cases and a Vancouver B2 classification was most common at n = 20. The majority
      of patients had revision arthroplasty, with a mean length of stay of 24 days for
      the whole cohort (9-42). Vancouver B3 fractures had the longest inpatient stay at
      a mean of 26 days. The mean cost of for a full revision of stem with additional
      plate and cable fixation was over ?27000 compared to ?14,600 for ORIF and cable
      fixation based on length of hospital stay. Conclusion: The prolonged length of
      stay associated with Vancouver B2 and B3 fractures leads to increased costs to
      the healthcare service. Accurately calculating the costs of total treatment for
      periprosthetic fractures is difficult due to a lack of transparency around
      implant and staffing costs. However, as we can expect increasing incidence of
      periprosthetic fractures presenting in the coming years it is paramount that we
      make financial provisions within healthcare budgets to ensure we can treat these
      patients appropriately.

PMID- 29657454
TI  - Association between reduced trunk flexibility in children and lumbar stress
      fractures.
AB  - Background: We noticed that most of active sports children with low back pain
      (LBP) have muscle tightness around the pelvis and reduced trunk flexibility.
      Abnormalities in short-time inversion recovery (STIR) images on magnetic
      resonance imaging (MRI) can show stress fracture. Therefore, we investigated the
      associations among LBP, trunk flexibility, and lumbar stress fractures. Methods:
      A total of 130 patients under the age of 18 years complained of LBP were
      investigated in STIR MRI images. Among these 130 patients, 65 cases of lumbar
      stress fracture were diagnosed and 65 cases were not diagnosed as a lumbar stress
      fracture. We compared between a group suspected of stress fracture (suspected
      group) and a group of stress fracture(stress fracture group)about their trunk
      flexibility. These groups were investigated about their initial trunk flexibility
      about below items; Finger floor distance (FFD), Heel to buttock distance (HBD),
      straight leg raising (SLR). Results: Significant differences were observed
      between suspected group and stress fracture group about every items; SLR (P <
      0.001), FFD (P < 0.01), HBD (P < 0.002). Most cases of stress fracture group had
      reduced trunk flexibility, and low flexibility in pelvic area muscles was
      observed in 93.8% (61/65) of cases at the initial examination. Otherwise, that of
      suspected group was 73.8%(48/65). Conclusions: Most patients of lumbar stress
      fracture had reduced trunk flexibility, and their reduced trunk flexibility might
      not be caused by LBP. In the early diagnosis of lumbar stress fractures using
      STIR MRI images, there were indicated that reduced trunk flexibility was one of
      helpful item for lumbar stress fracture.

PMID- 29657455
TI  - Dynamic leg length asymmetry during gait is not a valid method for estimating
      mild anatomic leg length discrepancy.
AB  - The purpose of this study was to test the validity of dynamic leg length
      discrepancy (DLLD) during gait as a radiation-free screening method for measuring
      anatomic leg length discrepancy (ALLD). Thirty-three subjects with mild leg
      length discrepancy walked along a walkway and the dynamic leg length discrepancy
      (DLLD) was calculated using a motion analysis system. Pearson correlation and
      paired Student t-tests were applied to calculate the correlation and compare the
      differences between DLLD and ALLD (alpha = 0.05). The results of our study showed
      DLLD is not a valid method to predict ALLD in subjects with mild limb
      discrepancy.

PMID- 29657456
TI  - Restoring femoral offset is the most important technical factor in preventing
      total hip arthroplasty dislocation.
AB  - Purpose: Our aim was to determine if acetabular component position, femoral
      offset restoration, or leg-length equality is most important for total hip
      arthroplasty (THA) stability. Methods: A matched case (n = 67)-control (n = 247)
      design and conditional logistic regression model were used to examine risk
      factors for dislocation in primary THA. Results: When femoral offset was at least
      3 mm greater than that of the contralateral hip, risk of dislocation was lower (p
      = 0.0192). Neither leg-length difference nor acetabular component abduction or
      version angle was associated with dislocation. Conclusions: Our data suggest
      restoring femoral offset is the most important technical factor in preventing THA
      dislocation.

PMID- 29657457
TI  - Effect of stem alignment on long-term outcomes of total hip arthroplasty with
      cementless Bi-Metric femoral components.
AB  - We investigated the effects of varus-valgus alignment on the long-term outcomes
      after cementless total hip arthroplasty (THA) using a porous coated version of Bi
      Metric(r) femoral stems. The Kaplan-Meier survival analysis was performed in 71
      hips. The survival rate with femoral revision for aseptic loosening as the end
      point was 100% at 17 years. Nevertheless, the initial stem alignment was more
      valgus in patients with the Engh grade III-IV stress shielding than patients with
      the Engh grade I-II. Our results suggest that valgus misalignment of cementless
      Bi-Metric stem might be a potential risk factor for the progression of stress
      shielding.

PMID- 29657458
TI  - Bizarre parosteal osteochondromatous proliferation: 16 Cases with a focus on
      histologic variability.
AB  - Bizarre parosteal osteochondromatous proliferation (BPOP) is a benign bone and
      cartilage forming tumor occurring on the surface of bones, predominantly on the
      hands and feet. A defining feature of BPOP is the purplish-blue mineralization of
      cartilaginous tissue, known as 'blue bone.' Here, we report on an institutional
      series of 16 cases of BPOP, including radiographic, histologic, and
      histomorphometric features. All tumors were composed of some element of bone,
      cartilage, fibrous tissue and 'blue bone,' though the amount of each tissue sub
      type varied widely. Some cases showed focal 'blue bone' only, however this was a
      defining feature in all cases.

PMID- 29657459
TI  - Stress radiographs for evaluating acromioclavicular joint separations in an
      active-duty patient population: What have we learned?
AB  - Introduction: Acromioclavicular (AC) joint separation is a common entity in
      athletic patient populations. The surgical treatment of these injuries varies
      based upon extent of injury, with numerous imaging modalities recommended to
      differentiate injury severity and treatment options. The use of weighted stress
      radiographs is controversial in the diagnostic evaluation of AC separation with
      previous consensus recommending against their use. No study to date has
      investigated the clinical utilization of diagnostic studies in the evaluation of
      AC joint separations in a military surgeon population. Methods: Thirty-eight
      shoulder or sports medicine sub-specialty certified orthopaedic surgeons on
      active service in the Army, Air Force, and Navy were surveyed on their evaluation
      and treatment protocols for AC joint injuries. Specifically analyzed were imaging
      choice including the use of weighted stress radiographs as well as treatment
      recommendations based upon Rockwood grade. Responses were recorded in addition to
      surgeon descriptive data. Responses were analyzed with descriptive statistics.
      Results: Thirty-seven of the identified thirty eight surgeons responded to the
      survey, for a 97% response rate. Of the group, 70% of surgeons were within 10
      years of completing fellowship with an estimated average of 15 AC joint
      separations treated annually. Plain radiographic examination was relied upon by
      48% of surgeons for treatment of AC joint separation with 13% using weighted
      stress radiographs. Overall, 10% of surgeon stated that their treatment plan
      would vary based upon results from a weighted stress view. 51% of surgeons
      included magnetic resonance imaging in their diagnostic approach of these
      injuries. Treatment recommendation varied according to injury severity with 78%
      preferring nonoperative treatment for acute Grade III injuries with 86% waiting a
      minimum of 3 months before proceeding with operative treatment. For Grade V
      injuries, 81% of surgeon preferred operative treatment, with 59% incorporating a
      soft-tissue graft in their repair or reconstructive procedure. Discussion: This
      study identified substantial practice variation amongst military surgeons
      treating a relatively homogenous population with AC joint separations, reflective
      of a lack of definitive evidence to guide diagnosis and treatment. Overall,
      nonoperative management is the preferred initial approach for Type III injuries
      and operative treatment is the preferred initial approach for Type V injuries.
      The diagnostic evaluation varied across the surgeon cohort, but 87% elected
      against the use of weighted stress radiographs for the evaluation of AC joint
      separations, with only 10% relying upon them to dictate their recommended
      treatment. Future research identifying optimal diagnosis and treatment of AC
      joint separations is needed.

PMID- 29657460
TI  - A quality improvement project decreases incidence of pulmonary embolism following
      arthroplasty.
AB  - Objective: To develop a quality improvement initiative to reduce the incidence of
      pulmonary embolism (PE) following elective lower extremity joint replacement
      surgery. Methods: 866 Patients undergoing a total knee or total or partial hip
      replacement surgery at a from 2014 to 2016 were included in this prospective pre
      post interventional study. Results: There were 13 PE's before the intervention
      and 2 after the intervention. The incidence of PE was significantly higher prior
      to the intervention (2.8% vs. 0.7%; p = 0.044). Conclusions: Our results suggest
      that our bundle of interventions was successfully implemented and helped to
      reduce the incidence of pulmonary embolism following surgery.

PMID- 29657461
TI  - Growth modulation for coronal deformity correction by using Eight Plates
      Systematic review.
AB  - Introduction: Coronal deformities are commonly encountered in paediatric
      orthopaedics and surgical treatment is indicated for severe deformities causing
      pain, function and cosmetic problems. In a growing bone, major surgical
      intervention like osteotomy with internal or external fixation can be avoided by
      growth modulation (hemiepiphysiodesis) using 8-plates. Our aim is to review the
      published literature on the use of 8-plates for deformity correction. Methods: We
      conducted a systematic review on 8-plate growth modulation for coronal deformity
      correction. We carried out detailed literature search on PubMed, Google Scholar,
      EMBASE, and Cochrane databases. We analysed selected studies for patient
      demographics, rate of deformity correction, clinical outcome and complications.
      Results: We identified seven studies using 8-plate for deformity correction
      involving 215 patients (350 Limbs). The mean age was 9.5 years (2-16 years M/F
      Ratio 1.1:1); underlying aetiology was Idiopathic in 33% and Pathological 67%
      cases. The deformities were successfully corrected in 196/215 patients (91.2%)
      and partial/no correction in 19/215 patients (8.8%). The mean time to correction
      was 15.3 Months (10.3-25) and follows up of 18.9 months (12.4-24). The deformity
      corrected at 1.28  degrees /month (0.93-1.53), lateral distal femoral angle
      changed at 0.87 degrees /month (0.65-1.0) and medial proximal tibial angle
      changed at 0.72 (0.5-1). Complications were reported in 12/215 patients (5.6%)
      including hardware failure in 5, overcorrection/leg length difference in 5,
      infection 1 and stiffness 1. The rebound was reported in 8 patients (3.7%).
      Conclusion: Growth modulation with 8-plates has high efficacy and low
      complications for deformity correction; and has been used widely across all
      paediatric age groups and aetiology. The literature is mostly retrospective and
      heterogeneous to develop age and aetiology specific recommendations.

PMID- 29657462
TI  - Computed tomography findings of subchondral insufficiency fractures of the
      femoral head.
AB  - Objectives: The objective of this study was to describe the appearance of
      Subchondral insufficiency fracture (SIF) by computed tomography (CT). Methods:
      Images of 52 consecutive patients diagnosed with SIF were retrospectively
      reviewed. CT was available for five patients (7 cases). Results: Corresponding to
      a low-intensity band on MR images, a radiolucent or sclerotic band was observed
      on CT images. Conclusion: The present study is the first to report CT findings of
      SIF. A radiolucent or sclerotic band was observed on CT images. The results of
      the present study provide useful information for diagnosis of SIF.

PMID- 29657463
TI  - Survey of shoulder arthroplasty surgeons' methods for infection avoidance of
      Propionibacterium.
AB  - Introduction: Propionibacterium acnes infection after shoulder arthroplasty
      remains a source of morbidity. Determining practices amongst shoulder surgeons is
      the first step in developing infection-prevention best-practices. Methods: A
      survey was sent to a shoulder fellowship alumni group to determine their
      arthroplasty infection prevention methods. Results: 74% completed the survey.
      Cefazolin (90%), vancomycin (50%) and clindamycin (18%) were the most commonly
      used antibiotics, 61% utilized more than one antibiotic. Most (76%) reported
      using an experience-based protocol learned during residency/fellowship.
      Discussion and conclusion: There are no clear standards for prevention of
      Propionibacterium acnes infections in shoulder arthroplasty. There is a general
      non-scientific approach to the prevention of shoulder arthroplasty infection.

PMID- 29657464
TI  - Gait analysis methodology for the measurement of biomechanical parameters in
      total knee arthroplasties. A literature review.
AB  - Gait analysis using external skin markers provides scope for the study of
      kinematic and kinetic parameters shown on different total knee arthroplasties
      (TKA). Thus an appropriate methodology is of great importance for the collection
      and correlation of valid data. Calibration of equipment is of great importance
      before measurements, to assure accuracy. Force plates should be calibrated to
      1080 Hz and optoelectronic cameras should use 120 Hz frequency, because of the
      nature of gait activity. Davis model which accurately defines the position of the
      markers is widely accepted and cited, for the gait analysis of TKA's. To ensure
      the reproducibility of the measurement, a static trial at the anatomical position
      must be captured. Following, all acquisitions of dynamic data must be checked for
      consistency in walking speed, and abnormal gait style because of fatigue or
      distraction. To establish the repeatability of the measurement, this procedure
      must be repeated at a pre-defined number of 3-5 gait cycles. Anthropometric
      measurements should be combined with three-dimensional marker data from the
      static trial to provide positions of the joint's center and define anatomical
      axes of total knee arthroplasty. Kinetic data should be normalized to bodyweight
      (BW) and percentage of BW and height depending on the study. External moments
      should also be calculated by using inverse dynamics and amplitude-normalized to
      body mass (Nm/kg). Gait analysis using external skin markers provides scope for
      the study of biomechanical parameters shown on different TKAs. Thus a standard
      gait analysis methodology when measuring TKA biomechanical parameters is
      necessary for the collection and correlation of accurate, adequate, valid and
      reproducible data. Further research should be done to clarify if the development
      of a specific kinematic model is appropriate for a more accurate definition of
      total knee implant joint center in measurements concerning 3D gait analysis.

PMID- 29657465
TI  - Do demographic and perioperative parameters really affect the final outcomes of
      pediatric femur shaft fractures managed by elastic nails? A prospective study.
AB  - Objective: Pediatric femoral shaft fractures are more commonly treated with
      intramedullary titanium elastic nail system (TENS). Adhering to the principles,
      most studies had supported excellent results with this instrumentation and
      attributed the variation in age, weight, immobilization protocols, technical
      factors like fracture pattern, reduction and complications as reasons to poor
      outcomes in their individual studies. Hence, we wanted to identify the potential
      demographic and perioperative parameters that could affect the final outcomes in
      this cohort. Methods: A prospective (level III) study done in a single center
      between November 2013 and January 2017 on isolated closed femoral shaft fractures
      in patients of age between 6 and 15 years managed with TENS. The demographic and
      perioperative parameters were recorded. The patients were followed up regularly
      with plain radiographs. The final outcomes were computed at end of one year and
      recorded as poor, satisfactory and excellent as defined by Flynn criteria.
      Results: Among the thirty patients included, mean age was 8.2 years. 80% of the
      patients weighing over 40 kg had satisfactory to poor outcomes. (p = 0.005). 45%
      of patients with proximal and distal level fractures that were long oblique
      spiral or comminuted types had satisfactory outcomes; however it was not
      statistically significant. The mean delay to surgical fixation was 5.87 days,
      surgical time was between 45 and 150 min and open reduction was required in about
      17 cases (57%). Patients with immobilization beyond 6 weeks had satisfactory
      outcomes (p = 0.001). We had 5 patients with minor complications (4 bursitis and
      3 superficial infections) and one major complication (chronic osteomyelitis and
      deep venous thrombosis) leading to satisfactory and poor outcomes respectively.
      Significant osseous union was noted between 6 and 11 months with 97% of patients
      attaining union within 9 months. Conclusions: Intramedullary TENS is an excellent
      modality to treat femoral shaft fractures in patients of school going age.
      However, factors like weight of the patient >40 kg, immobilization beyond 6
      weeks, minor and major complications in the perioperative period could pose risks
      for poor to satisfactory outcomes and should be anticipated and explained
      accordingly.

PMID- 29657466
TI  - A long-term comparative study between two different designs of cemented stems:
      Distal-cylindrical versus distal-taper.
AB  - Introduction: The aim of this study was to calculate the wear rate of highly
      cross-linked polyethylene (HXLPE) and investigate long-term clinical and
      radiographic outcomes related to two femoral stem designs, the distal-cylindrical
      (DC) and distal-taper (DT) stems. Materials and methods: Outcomes for the DC and
      DT stems were evaluated in 110 patients, who underwent total hip arthroplasty
      using an HXLPE socket, over a 5-year follow-up period. There were 56 hips (53
      patients) in the DC group and 60 hips (57 patients) in the DT group. Clinical
      outcomes were measured using the Japanese Orthopaedic Association (JOA) score and
      radiographic changes. Polyethylene wear rate was calculated using a computer
      software. Results: The mean follow-up period was 135.7 and 124.0 months for the
      DC and DT groups, respectively. Both stem designs improved hip function. On
      radiographic assessment, osteolysis around the tip of the stem was more frequent
      in the DC than in the DT group. Three cases of aseptic loosening of the stem were
      identified in the DC group, and no cases were identified in the DT group. The 10
      year stem survival, using aseptic loosening as the primary endpoint, was 94.1%
      and 100% for the DC and DT groups, respectively (p = 0.06). The polyethylene wear
      rate was comparable for both stem groups. Conclusion: Better clinical outcomes
      were obtained with the DT stem than with the DC stem regardless of the equivalent
      polyethylene wear rate for the two designs. The DC shape of the stem may increase
      the risk of aseptic loosening.

PMID- 29657467
TI  - Painless period after Spitzy shelf operation for residual hip dysplasia-A long
      term study of 47 children and young adults.
AB  - Objective: To study the effects of the Spitzy shelf operation on hip pain.
      Method: A modified Spitzy shelf procedure was performed in 60 hips with residual
      hip dysplasia. The mean age at surgery was 11.7 years (range 5.5-22.4 years).
      Results: Twenty-one hips had pain preoperatively. One year postoperatively 57
      hips (95%) were painless. The mean postoperative painless period in patients with
      >10 years follow-up was 24.1 years (range 5.0-51.5 years). The only independent
      predictor of long duration of painlessness was preoperative CE angle >=10 degrees
      . Conclusion: The Spitzy procedure had favorable short- and long-term effects on
      hip pain.

PMID- 29657468
TI  - Changes in serum chromium levels over 12 years after Metasul metal-on-metal total
      hip arthroplasty.
AB  - We reported the longitudinal changes in serum chromium levels over a minimum of 7
      years postoperatively in five men and 25 women with a mean age of 60.3 years
      after primary unilateral total hip arthroplasty with a Metasul metal-on-metal
      articulation. The serum chromium ion level showed little variation (0.6-1.2
      MUg/L) from 2 to 12 years postoperatively in 16/30 patients after unilateral
      primary Metasul metal-on-metal total hip arthroplasty. On the other hand, the
      serum chromium level stayed high or showed gradual elevation in 8/30 patients,
      even though they had well-fixed and well-functioning prostheses.

PMID- 29657469
TI  - Anatomical differences in the bony structure of L5 and L4: A possible
      classification according to the lateral tilt of the pedicles.
AB  - The aim of this study is to underline the necessity of a better knowledge of
      pedicles anatomy in order to improve surgical treatment of spine disorders such
      us low back pain, spinal fractures and scholiosis. A classification of pedicles
      lateral tilt which could help surgeons before the application of screws during
      transpedicular fixation is reported. Anatomical differences in the orientiation
      of the pedicles of L5 and L4 have been found. For each patient that met the
      inclusion criteria underwent: Radiography of the lumbo-sacral region, CT
      examination, MRI acquisition. Patients were divided into three categories thanks
      to 3D direct volume rendering of CT scan. Subjects belonged to W-Type, V-Type and
      U-type depending on their morphometric features. The subdivision was further
      implemented with measurements of the distance between pedicles and adjacent
      nervous structures. Concerning L5, W-Type (WT) exhibited a lateral tilt of L5
      larger than 36 degrees , V-Type exhibited a lateral tilt of L5 from 30 degrees 
      to 36 degrees , U-type exhibited a lateral tilt of L5 smaller than 30 degrees .
      Concerning L4, WT exhibited a lateral tilt of 28.4 degrees , VT exhibited a
      lateral tilt of of 25.1, UT exhibited a lateral tilt of 22.2 degrees ; we assume
      that the degree of lateralization of L4 depends on the one of L5. The way the
      screw is applied during surgical treatment is clinically relevant, thus our
      classification may be very useful in order to decrease surgical risk and improve
      conditions of patients after surgical treatment.

PMID- 29657470
TI  - Influence of timing of surgery on Cauda equina syndrome: Outcomes at a national
      spinal centre.
AB  - Purpose: There is no doubt that the best outcome achieved in Cauda equina
      syndrome (CES) involves surgical decompression. The controversy regarding outcome
      lies with timing of surgery. This study reports outcomes on a large population
      based series. Timing of surgery, Cauda Equina syndrome classification based on
      British Association of Spine Surgeons (BASS) guidelines and co-morbid illness
      will be assessed to evaluate influence on outcome. Materials and methods: A
      retrospective review of all patients surgically decompressed for CES between
      01/01/2008 to 01/08/2014 was conducted. Patients with ongoing symptoms were
      followed up for a minimum of 2 years. Cauda Equina Syndrome (CES) was classified
      according to the BASS criteria: CES suspicious (CESS), incomplete (CESI) and
      painless urinary retention (CESR). Time and symptom resolution were assessed.
      Results: A total of 136 patients were treated for CES; 69 CESR, 22 CESI and 45
      CESS. There was no statistical difference in age, sex, smoking status and alcohol
      status with regards to timing of surgery. No correlation between increasing co
      morbidity score and poor outcome was demonstrated in any subgroupAll CESR/I
      patients demonstrated some improvement in bowel and bladder dysfunction post
      operatively. No significant difference in improved autonomic dysfunction was
      demonstrated in relation to timing of surgery. CES subclassification may predict
      outcome of non-autonomic symptoms. Statistically better outcomes were found in
      CESS groups with regards to post-operative lower back pain (P 0.049) and saddle
      paraesthesia (P 0.02). Conclusion: Surgical Decompression for CES is an effective
      treatment that significantly improves patient symptoms including bowel and
      bladder dysfunction Early surgical decompression <24 h from symptom onset does
      not appear to significantly improve resolution of bowel or bladder dysfunction.

PMID- 29657471
TI  - Arthroscopic knotless rotator cuff repair: Factors associated with construct
      selection and recent trends from a manual review of 1617 cases.
AB  - Purpose: Our aim was to identify predictors of construct selection and recent
      trends for arthroscopic knotless rotator cuff repair (RCR). Methods: A manual
      review of 1617 operative reports was performed. Results: A medium-sized tear had
      a threefold increase in odds of single row (SR) knotless repair (OR, 6.91; p =
      0.009) versus SR knotted (OR, 3.05; p = 0.003). Generalist orthopaedic surgeons
      were 79% less likely to perform SR knotless repairs versus sports medicine
      trained specialists (p < 0.001). Conclusion: There was a significant increase
      from 2009 to 2016 in SR knotless and double row medial row knotless constructs
      contrasting the declining use of the SR knotted technique.

PMID- 29657472
TI  - Early determinants of long-term clinical outcome after cartilage repair surgery
      in the knee.
AB  - Purpose: To identify early determinants of clinical outcome after knee cartilage
      repair. Methods: 205 patients were evaluated before surgery and at median 14
      years follow-up. Results: Baseline factors predicting a good outcome were: single
      lesion; normal appearing cartilage surrounding the lesion; high baseline Lysholm
      score; short duration of symptoms; non-involvement of the patella-femoral joint;
      young age; and small defect. Factors predicting a poor outcome were: multiple
      lesions; low baseline Lysholm score; degenerative cartilage surrounding the
      lesion; long symptom duration; meniscal lesion; and large defect. Conclusions:
      The choice of surgical method seem to be less important than other patients
      specific predictors. Level of evidence: Case series, Level IV.

PMID- 29657473
TI  - Risk factors for complications after primary repair of Achilles tendon ruptures.
AB  - Purpose: To identify patient characteristics associated with adverse events in
      Achilles tendon rupture (ATR) surgical repair cases. Methods: A high risk (HR)
      cohort group of ATR patients were compared to healthy controls in the ACSNSQIP
      database with multivariate regression analysis. Results: Overall, 2% (n = 23) of
      the group sustained an AE postoperatively, most commonly superficial SSI (0.9%, n
      = 10). Multivariate analysis did not reveal any patient characteristics to be
      significantly associated with the occurrence of an AE or superficial SSI.
      Conclusions: Obesity, diabetes and a history of smoking did not predispose
      patients to significantly more AEs in the 30 day postoperative period following
      ATR repair in this study.

PMID- 29657474
TI  - Analysis of a generic talar prosthetic with a biological talus: A cadaver study.
AB  - Treatment for talar avascular necrosis is challenging. This study evaluates the
      feasibility of a generic talar implant by cadaveric assessment. Ten cadaveric
      ankles were CT-scanned to determine talar implant size. The opposite ankles were
      CT-scanned with the biological talus and then with the implant. 3D ankle geometry
      was reconstructed and implant position was compared to the biological talus
      position. The averages among specimens' positive and negative average-deviations
      were 0.91 mm and 0.70 mm. Seventy percent of talar dome deviations between the
      biological talus and implant were within an acceptable range. This study yields
      promising results to support a generic talus bone prosthetic.

PMID- 29657476
TI  - Platelet rich plasma injections for lateral epicondylitis of the elbow reduce the
      need for surgical intervention.
AB  - Objective: We aimed to assess the effectiveness of PRP injections in lateral
      epicondylitis of the elbow as it was felt after PRP introduction the numbers of
      patients requiring surgery for had reduced. Methods: We conducted a retrospective
      review of cases from the 1st January 2008 to 31st December 2015. The numbers of
      patients undergoing surgical release and the numbers of patients requiring PRP
      injections were recorded each year and the numbers of patients requiring surgery
      was compared pre and post PRP injection to ascertain if PRP introduction reduced
      surgical intervention. Results: Prior to PRP, a yearly mean of 12.75 patients
      underwent surgery, since PRP this reduced to 4.25 patients, P < 0.001. This leads
      to an absolute risk reduction of 0.773 and number needed to treat of 1.3. PRP
      injection successfully reduced symptoms in 56/64 (87.5%) patients in our study.
      Conclusion: We consider PRP injection, for intractable lateral epicondylitis of
      the elbow, not only a safe but also very effective tool in reducing symptoms and
      have shown it has reduced the need for surgical intervention in this difficult
      cohort of patients.

PMID- 29657475
TI  - Incidence of tendon rupture following volar plate fixation of distal radius
      fractures: A survey of 2787 cases.
AB  - This study assessed the comprehensive incidence of tendon rupture following volar
      locking plate (VLP) surgery for a large number of patients with distal radius
      fractures (DRFs) at multiple facilities in one prefecture, Japan. During the 4
      year period, 2787 patients with DRFs underwent fixation using VLP. The overall
      incidence rates of rupture of the FPL, the extensor pollicis longus, the flexor
      digitorum profundus of the index finger, and the extensor digitorum communis were
      0.35% (10 patients), 0.29% (8 patients), 0.04% (1 patient), and 0.04% (1
      patient), respectively.

PMID- 29657477
TI  - Evaluation of the Multi-Attribute Prioritisation Tool for Total Joint
      Replacement.
AB  - Rationale aims and objectives: The demand for arthroplasty is increasing and will
      continue to rise with an ageing population. Obesity and lengthy waiting time for
      Total Joint Replacement (TJR) have been associated with poorer outcomes
      postoperatively. This study aimed to evaluate the Multi-Attribute Prioritisation
      Tool (MAPT) for TJR patients. The primary objective was to explore if patients
      prioritised by the MAPT had an improvement in score post-operative. Further to
      identify any relationship between MAPT score and length of time on the waiting
      list or obesity. Method: This retrospective cohort study included 308 patients
      undergoing total hip (n = 114) or total knee (n = 194) arthroplasty. We examined
      preoperative and postoperative MAPT scores of patients who had total hip or total
      knee arthroplasty. After assessing the difference between postoperative and
      preoperative MAPT scores, patients scores were compared to BMI and waiting time
      classes. BMI was allocated to less than 30, 30-35, 35-40 and greater than 40.
      Duration of time on the waiting list was allocated to less than 6 months and
      greater than 6 months. Results: THA and TKA patients MAPT scores improved from a
      preoperative score of 71.39-5.26 postoperative and 54.11 to 7.13 respectively.
      Patients whose MAPT scores placed them in the high priority category had a
      significant relationship with length of time on the waiting list (p < 0.01).
      There were no significant differences between length of time on the waiting list
      and improvement scores for low priority and middle priority patients. BMI had
      minimal effect on patients improvement score postoperative. Conclusion: TJR
      patients prioritised by the MAPT questionnaire do experience pain relief as
      portrayed by a reduction in postoperative MAPT score. A longer length of time on
      the waiting list seems to effect the improvement a high priority patient can have
      postoperative.

PMID- 29657478
TI  - Cryopreserved bone allograft for the treatment of shoulder instability with
      glenoid defect.
AB  - The purpose of this study was to examine outcomes after cryopreserved tri
      cortical iliac crest allograft reconstruction for glenoid bone loss in patients
      with shoulder instability. 10 patients completed the required assessments at a
      mean follow up of 4.5 years. At final follow up, mean ASES was 92 +/- 12, mean
      WOSI was 315 +/- 319, with good range of motion. None of the final radiographs
      demonstrated graft resorption or failure of hardware. The data demonstrated that
      patients who were treated with glenoid bone grafting with cryopreserved tri
      cortical iliac crest allograft can expect good range of motion and functional
      capacity.

PMID- 29657479
TI  - Minimally invasive (MIS) Tonnis osteotomy- A technical annotation and review of
      short term results.
AB  - Aims: We detail a modified single incision approach to perform the Tonnis triple
      pelvic osteotomy by a minimally invasive approach. Patients and Methods: 12
      children underwent minimally invasive Tonnis Osteotomy. There were five boys and
      seven girls in this study group. Average age was 11 years (9-15 years) at the
      time of surgery. Mean follow-up was 20.5 months (13-39 months). Results: The
      average preoperative Antero-Posterior (AP) Centre Edge (CE) angle was -8.8
      degrees  (-38.6 degrees -18 degrees ), the average post-operative AP CE angle was
      29.7 degrees  (25.1 degrees -43.7 degrees ). The average preoperative lateral CE
      angle was -4.7 degrees  (-16 degrees -0 degrees ), the average postoperative
      Lateral CE angle was 28.5 degrees  (21.3 degrees -37.4 degrees ). The Sharp's
      angle before and after surgery were 55.7 degrees  (51.3 degrees -66 degrees ) and
      32.4 degrees  (16.1 degrees -40.1 degrees ) respectively. The mean Tonnis angle
      before and after the osteotomy were 28.86 degrees  (19.7 degrees -43.4 degrees )
      and 6.3 degrees  (0.5 degrees -9.4 degrees ) respectively. There was one major
      complication with sciatic nerve palsy which is in the recovery phase on followup
      and six minor complications including two cases of transient lateral femoral
      cutaneous nerve injury, two cases of ischial non-union, over granulation of the
      wound in one case, and metalwork irritation in one case. Conclusion: We have
      described a minimally invasive Tonnis osteotomy as a viable option based on our
      results. This technique is recommended for those who are conversant with the
      traditional pelvicosteotomies.

PMID- 29657480
TI  - A novel method for reducing gap formation in tendon repair.
AB  - Background: This study investigates gap formation in tendon repair using a novel
      tensioning method. Hypothesis: The novel stitch will demonstrate less gap
      formation than the other suture configurations tested. Methods: Porcine tendons
      stitched with classic Krackow stitch configurations were compared to a Krackow
      stitch modified with a proximal Tension-Assist Loop. Each group was cyclically
      loaded followed by analysis of the tendon-suture construct for gap formation.
      Results: The Tension-Assist Loop group produced significantly less gap formation
      than each of the other stitch groups. Conclusion: Decreasing early gap formation
      may be beneficial in allowing early rehabilitation and range of motion.

PMID- 29657481
TI  - Getting back in the game after humeral head resurfacing.
AB  - Background: Aim of this investigation was to analyze whether patients undergoing
      humeral head resurfacing (HHR) surgery are able to successfully return to their
      sports and occupation afterwards. Materials and methods: Fifty patients treated
      with CUP (HHR) arthroplasty were included. Two groups were built: Patients who
      have participated in sports less than 5 years prior surgery (Group 1: n = 42
      (84%)) and patients who have never participated in sports (Group 2: n = 8 (16%)).
      Evaluation was based on a questionnaire asking for types of sports, frequency,
      time to return to sports and work as well as limitations in work life. Results:
      Mean age at the time of surgery was 58.6 (36-84) years in Group 1 and 65 (56-75)
      years in Group 2. Mean time follow-up was 5.5 years (2.5-12) years. Twenty-seven
      (64%) patients in Group 1 participated in sports right before surgery. Twenty-one
      patients (50%) returned to sports after surgery. The returning rate was 78%.
      Seven (17%) patients in Group 1 stated that the reason they underwent shoulder
      replacement surgery was to continue to participate in sports. Swimming and skiing
      were two of the most favorable sports. Two (4%) patients had to change their
      profession due to surgery. Most of the patients were retired at follow-up.
      Conclusion: Most of the active patients undergoing HHR surgery are successfully
      able to return to their sports activities after surgery. Patients employed were
      able to return to their occupation after surgery. Many patients were already
      retired at the time of follow up.

PMID- 29657483
TI  - Imaging the Anterior Cruciate Ligament-Points to Ponder.

PMID- 29657482
TI  - Functional and radiological outcome in management of compound tibia diaphyseal
      fracture with AO monolateral fixator versus Limb reconstruction system.
AB  - Introduction: Tibia being the most common fractured long bone represents 36.7% of
      all long bone fractures in adults with open fracture comprises 23.5% of all
      tibial shaft fracture. The lack of the muscular covering over anteromedial aspect
      of the tibia and poor blood supply predispose open tibial fractures to a 10-20
      fold increased risk of developing infection than open fracture in any other
      anatomical areas and a nonunion rate as high as 28% has been reported in the
      literature. Methods: We did a prospective study at our institute from 2014-2016
      comprising 40 patients with compound tibia diaphyseal fracture managed with AO
      monolateral external fixator (Group 1) (n = 20) and Limb reconstruction system
      (Group 2) (n = 20) as primary and definitive tool. Final assessment for bone
      results and functional results were done using ASAMI (Association of the study
      and application of the method of Ilizarov) score. Results: In our study bony
      outcome by ASAMI score shows 6 (30%) patients had Excellent, 5 (25%) patients had
      Good and 9 (45%) had Poor bony outcome from Group I. In group II, 12 (60%)
      patients had Excellent, 4 (20%) patients had Good, 2 (10%) patients had Fair, and
      2 (10%) had Poor bony outcome. The functional outcome by ASAMI score shows 3
      (15%) patients had Excellent, 8 (40%) patients had Good, 5 (25%) patients had
      Fair, 3 (15%) had Poor bony outcome from Group I. In group II, 9 (45%) patients
      had Excellent, 7 (35%) patients had Good, 2 (10%) patients had Fair, and 2 (10%)
      had Poor functional outcome. Conclusion: Limb reconstruction system (LRS) offers
      several advantage over AO monolateral external fixator such as ease of
      application, versatility, stronger fixation, less fixator related complications,
      early weight bearing and early bony union for management of compound tibia
      diaphyseal fracture as primary and definitive tool.

PMID- 29657484
TI  - Mining Unique-m Substrings from Genomes.
AB  - Unique substrings in genomes may indicate high level of specificity which is
      crucial and fundamental to many genetics studies, such as PCR, microarray
      hybridization, Southern and Northern blotting, RNA interference (RNAi), and
      genome (re)sequencing. However, being unique sequence in the genome alone is not
      adequate to guaranty high specificity. For example, nucleotides mismatches within
      a certain tolerance may impair specificity even if an interested substring occur
      only once in the genome. In this study we propose the concept of unique-m
      substrings of genomes for controlling specificity in genome-wide assays. A unique
      m substring is defined if it only has a single perfect match on one strand of the
      entire genome while all other approximate matches must have more than m
      mismatches. We developed a pattern growth approach to systematically mine such
      unique-m substrings from a given genome. Our algorithm does not need a pre
      processing step to extract sequential information which is required by most of
      other rival methods. The search for unique-m substrings from genomes is performed
      as a single task of regular data mining so that the similarities among queries
      are utilized to achieve tremendous speedup. The runtime of our algorithm is
      linear to the sizes of input genomes and the length of unique-m substrings. In
      addition, the unique-m mining algorithm has been parallelized to facilitate
      genome-wide computation on a cluster or a single machine of multiple CPUs with
      shared memory.

PMID- 29657485
TI  - Virtopsy: An integration of forensic science and imageology.
AB  - In an era where noninvasive and minimally invasive techniques are heralding
      medical innovations and health science technology, necrological analysis is not
      bereft of this wave. Virtopsy is virtual autopsy. It is a new-age complimentary
      documentation approach to identify and analyze the details of demise. Utilizing
      virtual autopsy for orofacial forensic examination is an emerging specialty which
      holds a plethora of potential for future trends in forensic science. Being a
      noninvasive technique, it is a rapid method which facilitates the medicolegal
      process and aids in the delivery of justice. The present article is an overview
      of this emerging methodology.

PMID- 29657486
TI  - Current trends in forensic odontology.
AB  - Forensic odontology is an evolving science and has a greater scope of
      development. It has established as an indispensable science in medico-legal
      matters and in the identification of the dead person. The dental tissues are
      often preserved even if the deceased person is skeletonized, decomposed, burnt,
      or dismembered. Various methods have been developed to determine age, sex, and
      ethnicity of the person, using dental tissues. Data collection methods and
      supplementary technologies used in forensic dental identification have undergone
      significant transformation. This article provides an overview of the evolving
      trends in conventional methods, and the recent concepts used in forensic
      odontology.

PMID- 29657487
TI  - Anthropometric study using craniofacial features to determine gender in Lucknow
      population.
AB  - Background: Gender is one of the main characteristics analyzed for positive human
      identification in forensic medicine. The methods involving physical anthropology
      present high rate of accuracy for human identification and gender estimation.
      Aim: This study aimed to determine gender through different craniofacial
      variables using physical anthropometric methods. Materials and Methods: A cross
      sectional study was conducted among 100 individuals (50 males and 50 females) in
      Lucknow. Variables studied through physical anthropometry in both the genders
      were facial height, nasion-to-menton distance, interzygomatic arch width, and
      intercanthal width using a digital sliding caliper. All the measurements were
      taken twice. The final value was the average of the two obtained values. Results:
      Comparing the mean craniofacial features between two genders, t-test revealed
      significantly higher facial height, pronasale-to-menton distance, and
      interzygomatic width in males as compared to females, but the mean intercanthal
      width was found to be the same. Pearson's correlation analysis revealed a
      positive correlation between facial height and pronasale-to-menton distance,
      facial height and interzygomatic width, pronasale-to-menton distance and
      interzygomatic width, and interzygomatic width and intercanthal width.
      Conclusion: The craniofacial features may serve as diagnostic markers for gender
      identification and can be used interchangeably.

PMID- 29657488
TI  - Sex determination from mesiodens of Indian children by amelogenin gene.
AB  - Context: The identification of sex is the first and the foremost step in forensic
      science. Teeth consist of enamel which is the hardest tissue available in the
      body, protector of DNA presents in pulp tissue at the time of exposure of tooth
      to adverse conditions. Teeth can be stated as a sealed box of mystery as it
      contains various human and bacterial DNA for molecular utilization. Aim and
      Objective: The aim is to determine sex from mesiodens on the basis of gene
      identification by the polymerase chain reaction (PCR). Settings and Design: Total
      number of sample was 8 human-extracted mesiodens. DNA was isolated and was
      subjected to PCR analysis with use of predesigned primers for amelogenin (AMEL) X
      and AMEL Y genes. Results: Isolation of genomic and mitochondrial DNA from
      mesiodens was successful in six samples (75%). In samples, quantity of DNA
      present was also calculated. Conclusion: Mesiodens are a good source of DNA and
      are a very useful tool in identification of sex using PCR analysis which was
      simple and effective. Hence, the procedure presented in the present study can be
      applied for extraction of DNA and identification of sex for forensic purpose.

PMID- 29657489
TI  - A radiographic survey of agenesis of the third molar: A panoramic study.
AB  - Purpose: It is a well-known fact that nature tries to eliminate what is not in
      use. Because of this, the number of certain teeth which are no longer necessary
      for function are either getting increasingly impacted or are not developing at
      all. This is especially the case where third molars are concerned. Furthermore,
      the presence or absence of the third molar is significant to all branches of
      dentistry and in particular, forensic dentistry. Objectives: The objectives of
      this study is to assess (1) The prevalence of third molar agenesis in population
      of age group 18-25 years. (2) The genderwise difference of third molar agenesis.
      (3) The difference between maxilla and mandible. Materials and Methods: Dental
      patients, who are advised or referred for orthopantomograph, visited to the
      Department of Oral Medicine and Radiology were included in the study. The study
      population comprised 300 patients. Statistical Analysis: The data obtained was
      tabulated and subjected to statistical analysis. SPSS version 17 software was
      used for the analysis of the data. The Chi-square test was used for the same.
      Results: The incidence of agenesis of the third molar is significantly higher for
      tooth number 18 (P < 0.001). Overall, it is significantly higher among females
      compared to the males (P < 0.001) in our study population. Conclusion: (1) The
      present study reports 46.7% agenesis of the third molar. (2) The frequency of
      third molar agenesis was found significantly greater in the females. (3) Third
      molar agenesis showed a greater predilection in maxilla compared to mandible.

PMID- 29657490
TI  - Mandibular canine index: A study for gender determination in Gandhinagar
      population.
AB  - Introduction: One of the important pieces of information gathered from tooth
      analysis is the sex of an individual. In most human living populations,
      mandibular canines show the greatest dimorphism and greatest dimensional
      differences between males and females. In view of these facts, the aim of this
      study was to establish the standard mandibular canine index (MCI) and estimate
      the sexual dimorphism in the population of Gandhinagar district of Gujarat state.
      Materials and Methods: The study consisted of 400 subjects, 200 males and 200
      females in the age group of 20-40 years. The mesiodistal (MD) width of the right
      and left canine and the intercanine distance were measured. These values were
      used to derive the MCI and establish the amount of sexual dimorphism exhibited by
      the mandibular canine. Results: The MD crown width of the permanent mandibular
      right and left canines as well as mandibular intercanine distance of the males
      was found to be larger in size than in the females. The right mandibular canine
      exhibited 8.42% of sexual dimorphism while the left mandibular canine exhibited
      8.40% of sexual dimorphism. The intercanine distance showed 2.75% of sexual
      dimorphism. The value of standard MCI derived using the formula devised by Rao et
      al. was 0.254 mm for the population residing in the Gandhinagar district.
      Conclusion: The present study supports the usefulness of the MCI in gender
      determination. The method of using mandibular canine indices is advantageous as
      it is easy, rapid, and cost-effective, requires no elaborate apparatus, and is
      suited for situations where large a number of samples have to be analyzed.

PMID- 29657491
TI  - Age estimation using exfoliative cytology and radiovisiography: A comparative
      study.
AB  - Introduction: Age estimation is one of the essential factors in establishing the
      identity of an individual. Among various methods, exfoliative cytology (EC) is a
      unique, noninvasive technique, involving simple, and pain-free collection of
      intact cells from the oral cavity for microscopic examination. Objective: The
      study was undertaken with an aim to estimate the age of an individual from the
      average cell size of their buccal smears calculated using image analysis
      morphometric software and the pulp-tooth area ratio in mandibular canine of the
      same individual using radiovisiography (RVG). Materials and Methods: Buccal
      smears were collected from 100 apparently healthy individuals. After fixation in
      95% alcohol, the smears were stained using Papanicolaou stain. The average cell
      size was measured using image analysis software (Image-Pro Insight 8.0). The RVG
      images of mandibular canines were obtained, pulp and tooth areas were traced
      using AutoCAD 2010 software, and area ratio was calculated. The estimated age was
      then calculated using regression analysis. Results: The paired t-test between
      chronological age and estimated age by cell size and pulp-tooth area ratio was
      statistically nonsignificant (P > 0.05). Conclusion: In the present study, age
      estimated by pulp-tooth area ratio and EC yielded good results.

PMID- 29657492
TI  - Estimation and quantification of human DNA in dental calculus: A pilot study.
AB  - Context: Identification using DNA has proved its accuracy multiple times in the
      field of forensic investigations. Investigators usually rely on either teeth or
      bone as the DNA reservoirs. However, there are instances where the skeletal or
      dental remains are not available or not preserved properly. Moreover, due to
      religious beliefs, the family members of the dead do not allow the investigating
      team to damage the remains for the sole purpose of identification. Aim: To
      investigate the presence of human DNA in dental calculus and to quantify the
      amount, if present. Materials and Methods: This prospective single-blinded pilot
      study included twenty subjects selected from the patients visiting a dental
      college. The samples of dental calculus were collected from the thickest portion
      of calculus deposited on the lingual surfaces of mandibular incisors. These
      samples were decontaminated and subjected to gel electrophoresis for DNA
      extraction. Results: DNA was found in 85% cases. The amount of DNA varied from 21
      to 37 MUg/ml of dental calculus. Conclusion: Dental calculus is a rich reservoir
      of human DNA.

PMID- 29657493
TI  - Evaluation of sexual dimorphism in arch depth and palatal depth in 500 young
      adults of Marathwada region, India.
AB  - Context: In exhibiting gender dimorphism, the bony pelvis and skull give the most
      reliable results from morphometric analysis. Palatal dimensions were reported to
      exhibit racial difference and sexual dimorphism in several studies. Aim: The aim
      of the present study was to measure the maxillary arch depth and palatal depth in
      Indian population to assess their use as a tool for sexual dimorphism. Materials
      and Methods: Two hundred and fifty males and 250 females in the age group of 17
      25 years were enrolled in the study, and impressions of maxillary arch were made.
      Measurement of palatal depth and maxillary arch depth was carried out at specific
      reference points using Korkhaus compass and digital caliper, respectively. The
      comparison of maxillary arch depth and palatal depth values was done using
      independent t-test. P < 0.05 was considered statistically significant. Diagnostic
      performance of significantly different variable was quantified by plotting
      "receiver operating characteristic" (ROC) curve. Results: Arch depth mean values
      were significantly higher in males than females. However, palatal depth mean
      values, though higher in males, were not significant. Area under the curve in ROC
      curve for maxillary arch depth was found to be 0.76, indicating sufficiency of
      discriminatory power of this variable. Conclusion: The present study showed that
      maxillary arch depth can be used as a tool for sex determination along with other
      morphometric methods. Mean value of both maxillary arch depth and palatal depth
      can be used as the baseline value for given population to be used as a reference
      for further studies.

PMID- 29657494
TI  - Stereomicroscopic study on unsectioned extracted teeth.
AB  - Introduction: Age has been considered as a reliable marker for establishing the
      identity of a person in the field of forensic medicine. Teeth are useful skeletal
      indicators of age at death since it can survive for decades. Nondestructive
      methods ensure the evident preservation of dental hard tissues that reflect age
      changes from the cradle to the grave. Therefore, an attempt was made for
      estimating the age using the nondestructive method. Aims and Objectives: The aim
      of this study to assess whether physiological changes of the teeth allow possible
      correlation for accurate age estimation and to establish a graduation standard by
      microscopic observation for a better age correlation. Materials and Methods: The
      study was carried on 209 teeth samples extracted for orthodontic treatment or
      periodontal diseases comprised both maxillary and mandibular teeth across
      different age groups. The assessment of these changes was carried out by well
      established standard methods with some proposed modifications. Results: Pearson
      correlation analyses revealed root dentin translucency with the highest
      correlation (r = 0.97) followed by periodontal ligament attachment (r = 0.95),
      root dentin color (r = 0.95), and attrition being the least correlated (r =
      0.90). All the parameters taken for the study contributed to stepwise linear
      regression analysis (R = 0.98; P < 0.01) indicating a strongly positive
      relationship between age and the changes observed. A regression formula was
      obtained with mean error age difference +/-1.0 years. Conclusion: The present
      study showed that extracted tooth is highly significant in identifying the age
      without being sectioned or further processed and also signifies the use of
      microscope for observation of these changes, thus reducing the errors of
      calibrating the age.

PMID- 29657495
TI  - The effects of temperature on extracted teeth of different age groups: A pilot
      study.
AB  - Context: Type of dentition and age related changes may affect the behavior of
      dental hard tissues under thermal stress. Aim: This study was conducted to
      analyze the effects of varying temperatures on extracted teeth of different age
      groups in a simulated laboratory set up. Settings and Design: Experimental pilot
      study. Methods and Material: Extracted teeth from three age groups (deciduous,
      young permanent and adult permanent) were collected and were exposed to three
      different temperatures (400 degrees C, 700 degrees C and 1000 degrees C) in a
      laboratory set up. Post-test changes were analyzed visually and radiographically.
      Results: (1) The colour changes of the teeth may serve as an indicator for the
      temperature to which they were exposed. (2) Deciduous teeth tolerated thermal
      stress with lesser morphological changes compared to young and adult permanent
      teeth. (3) Coronal dentin of elderly permanent teeth appeared to be more
      resistant to thermal stress compared to that of young permanent teeth. (4) The
      root portion of the teeth showed better tolerance to temperature while crown was
      fragmented easily under thermal stress. Conclusion: The age factor and type of
      the dentition may influence the heat induced changes in teeth. These variables
      should be taken into consideration while applying comparative dental
      identification methods where dental hard tissues are exposed to extreme
      temperatures.

PMID- 29657496
TI  - Applicability of odontometric dimensions and indices in sexual dimorphism among
      Nalgonda population.
AB  - Background: Teeth morphology varies among different population groups as they are
      exposed to various environmental conditions. Teeth being the most stable and hard
      tissue, human identification can be made when the other tissues are unavailable.
      Odontometric analysis can be considered for anthropological and forensic
      investigations. Aim: The aim of this study is to assess the reliability of
      odontometric mesiodistal (MD) width dimensions and indices in sexual dimorphism
      among Nalgonda population. Materials and Methods: A total of 180 ideal study
      dental models of patients between the age range of 18 and 25 years were collected
      from the Department of Orthodontics. Selection criteria include teeth with Class
      I molar and canine relation, free of anomalies, or caries. Maximum MD widths of
      all teeth and arch parameters (intercanine width, interpremolar width, and
      intermolar width) were measured and incisor index, canine index, premolar index,
      and molar index were calculated. Sexual dimorphism was calculated using Garn and
      Lewis equation. Statistical Analysis: The recorded data were subjected to
      statistical analysis using independent unpaired t-test. Results and Conclusion:
      Mandibular canines followed by maxillary canines showed greater sexual dimorphism
      among all teeth. Maxillary right canine index, mandibular left canine index,
      maxillary right incisor index, inter premolar and intermolar widths showed
      statistically significant difference between males and females (P < 0.05). The
      results of this study revealed significant sexual dimorphism with the use of
      odontometric dimensions, canine index, incisor index, and arch parameters. These
      parameters could be used as adjunctive aids by the forensic expertise in human
      identification.

PMID- 29657497
TI  - Denture labels: Various types and their abilities to resist different assaults.
AB  - Introduction: The use of denture labels for the purpose of identification has
      been well documented. A number of labels for marking the denture are documented
      till date demonstrating the ease of fabrication and its potential value in
      identification. Therefore, it becomes essential that these denture labels fulfill
      the requisites of an ideal denture label and thus should be able to sustain the
      various assaults to which they might be subjected simulating a crime scene. Aim:
      The aim of this study was to determine the ability of various denture labels to
      withstand different types of assaults thereby evaluating the performance of
      routinely used denture labels. Materials and Methods: Four polymethylmethacrylate
      blocks were fabricated where the inclusion labels were incorporated on one side,
      and the surface labels were marked on the other side. Each of the blocks was then
      placed in different containers to be subjected to different assaults such as
      acid, alkali, water, and heat of increasing temperature. Results: Inclusion
      labels performed better as compared to surface marking labels. Among the
      inclusion labels, the metallic labels performed the best. Conclusion: The
      metallic inclusion labels were able to withstand most assaults than any other
      inclusion labels or surface marking labels. Due to easy availability, cost
      effectiveness, ease of incorporation and inertness, metallic labels are best
      suited as denture labels for personal identification.

PMID- 29657498
TI  - Odontometric sex estimation from clinically extracted molar teeth in a North
      Indian population sample.
AB  - Background: Different dental features have contributed significantly toward sex
      determination in the forensic anthropological contexts. Population-specific
      standards (discriminant functions or regression formulae) have been suggested for
      various population groups to identify the sex of an unknown individual from
      dental dimensions and other odontometric features. The main purpose of the
      present investigation was to examine the degree of sexual dimorphism exhibited by
      the human teeth of North Indians and identify importance as a forensic tool in
      sex determination. Materials and Methods: The linear and diagonal dimensions were
      recorded at both crown and cementoenamel junction levels of 58 upper and 72 lower
      molars of 130 Northwest Indian subjects (73 males and 57 females). The
      measurements were subjected to appropriate statistical analyses to estimate the
      sex estimation accuracy from lower and upper molars separately. Results:
      Univariate analyses revealed that molar teeth had greater dimensions in males
      than the females and the mesiodistal cervical diameter (MDCV) was found to be the
      most suitable variable for sex determination of the molars. The classification
      results were in agreement with the previously conducted studies. The index of
      sexual dimorphism (ISD) was calculated to be higher in lower molars than the
      upper molars, and the highest sex differences were observed for MDCV based on the
      ISD. The overall sex estimation accuracy obtained from multivariate discriminant
      function analysis and regression analysis of pooled data was 70.0% (74% males,
      64.9% females) and 66.9% (78.1% males, 52.6% females), respectively. Conclusions:
      Odontometrics can play a significant role in establishing the biological identity
      of an unknown individual even from a single tooth in the absence of other
      sophisticated molecular or biochemical techniques used for this purpose.

PMID- 29657499
TI  - Age estimation in Indian adults by the coronal pulp cavity index.
AB  - Background: Age estimation from tooth coronal index (TCI) using intraoral
      periapical radiographs by paralleling technique based on a reduction in the size
      of the dental pulp cavity with advancing age as a result of secondary dentin
      deposition. Aim and Objectives: The aim of this study is to estimate age for
      Indian adults using radiographs of mandibular first molar and second premolar
      teeth using coronal pulp cavity index. Materials and Methods: The study material
      consists of 400 intraoral periapical radiographs of mandibular second premolar
      and mandibular first molar from enrolled participants of either gender in the age
      group of 20-60 years. Statistical Analysis: Data analysis was done using SPSS
      (Statistical Package for Social Sciences), and Pearson's correlation coefficient
      (r) was used to find the correlation between age (years) and TCI. Results: TCI
      was computed for each tooth and regressed on the real age of the sample. The
      correlation coefficient "r" was -0.865 (for premolar combined sample) and -0.850
      (for molar combined sample). The obtained equations were tested on test sample of
      fifty teeth and age was determined. The absolute mean error between actual and
      predicted age for premolars was 6.72 months and for molars, it was 9 months.
      Conclusion: Age estimation using TCI is a precise, noninvasive, less time
      consuming, and an inexpensive method.

PMID- 29657500
TI  - Agro-toxicological aspects of coal fly ash (FA) phytoremediation by cereal crops:
      effects on plant germination, growth and trace elements accumulation.
AB  - A vegetative cover is a remedial technique utilized on coal fly ash (FA)
      landfills for soil stabilization and for the physical and chemical immobilization
      of contaminants. There is a great concern, that plants planted or voluntarily
      growing on media with high content of FA may absorb toxic amounts of Se and/or
      heavy metals. If such plants are ingested, it may result in toxicity to animals
      or humans. Despite these objections, the utilization of FA as a growth medium for
      plants is an attractive alternative for disposal of FA in landfills. We
      hypothesized that selected plants will grow in media containing FA and/or bottom
      ash (BA) from several sources. Two coal FA, one from Montana semi-bituminous coal
      and another from North Dakota lignite alone or in combination with BA from
      Montana semi-bituminous coal were tested as plant growth media for the following
      plant species: barley (Hordeum vulgare), oats (Avena sativa), rye (Secale
      cereale), wheat (Triticum aestivum), regreen; a hybrid between wheatgrass
      (Agropyron cristatum) and winter wheat (Triticum aestivum), and triticale; a
      hybrid between wheat (Triticum aestivum) and rye (Secale cereale). The
      concentration of Al, As, B, Ba, Be, Co, Cd, Cr, Cu, Mo, Pb, Sr, Ti, Tl, and V in
      growth media and in young plants was determined using Inducted Coupled Plasma
      Spectrophotometry (ICP). All tested plant species germinated and grow in FA
      and/or FA + BA containing media. However, germination and/or growth of the
      majority of tested plants were decreased by the presence of FA and/or BA in
      growth media. Concentration of all analyzed elements was greater in growth media
      containing FA and/or BA than in soil control, and also was greater in plants
      grown on medium containing FA and/or BA than in soil. These data demonstrate that
      tested plants can grow on media consisting of coal ash, and therefore these
      plants can be used to cover FA or BA residue piles.

PMID- 29657501
TI  - Evaluation of Bloodletting Cupping Therapy in the Management of Hypertension.
AB  - Background: Bloodletting cupping therapy (Hijama) is a traditional alternative
      medicine practiced in different cultures. Claims about the therapeutic efficacy
      of Hijama in hypertension are contradictory. The aim of this project was to
      determine if Hijama therapy is beneficial in the treatment of patients with
      hypertension. Materials and Methods: In this retrospective study, 60 files for
      patients treated for hypertension, aged 40-60 years and whose systolic blood
      pressure (SBP) is at least 140mm Hg, were used. The data from 30 patient files
      were obtained from three licensed Hijama centers (study group), whereas data from
      the rest of 30 patient files were collected from a hospital (control group). The
      data from Hijama centers included age, date of Hijama therapy, and blood pressure
      measured before each Hijama session. Both diastolic blood pressure (DBP) and SBP
      data were obtained over 3-month period. Results: The results showed a significant
      reduction in SBP (P value < 0.01) over three sessions of wet cupping (from 149.2
      to 130.8mm Hg), but this was not significant for DBP over three sessions (P =
      0.074). The study also found that the mean SBP in the study group was 9.6mm Hg
      less than that in the control group (130.8 vs. 140.4mm Hg, P = 0.019), whereas
      there was no significant difference in DBP between the study group and the
      control group (87.0 vs. 86.0mm Hg, P = 0.75). Conclusions: Our study shows clear
      relationship between Hijama and the reduction and control of SBP in patients with
      hypertension. Therefore, Hijama can be used as an adjunct to conventional
      therapy, which may allow downtitration of given doses of antihypertensive drugs.
      The possible association of SBP reduction by Hijama and pain reduction needs an
      investigation.

PMID- 29657502
TI  - Knowledge, Attitude, and Practice Regarding the Risk of Cardiovascular Diseases
      in Patients Attending Outpatient Clinic in Kuantan, Malaysia.
AB  - Background: Cardiovascular disease (CVD) is a leading cause of death around the
      world including Malaysia. Ischemic heart disease (IHD) is the single largest
      cause of death in the developed countries and is one of the main contributors to
      the disease burden in developing countries. Materials and Methods: This was a
      cross-sectional study conducted to determine knowledge, attitude, and practice
      (KAP) regarding the risk of CVD in patients attending an outpatient clinic in
      Kuantan, Malaysia. A total of 100 patients comprising 52 male and 48 female
      subjects were selected through convenient sampling method. Results: Of the total
      subjects, 86% were Malays. The mean scores (standard deviation) for KAP were
      60.75+/-4.823, 54.36+/-8.711, and 33.43+/-4.046, respectively, whereas the
      maximum scores obtained by the subjects for KAP were 71, 65, and 43,
      respectively. Regarding questions related to knowledge, 88% subjects knew
      irregular eating pattern can cause disease and the benefits of vegetable intake.
      Most subjects recognized that smoking and obesity were CVD risk factors.
      Regarding questions related to attitude, 96% agreed that exercise can prevent
      CVD. More than half of the subjects followed healthy lifestyle. There were
      statistically significant differences observed in knowledge level between sexes
      (P = 0.046) and races (P = 0.001). Nevertheless, there was no statistically
      significant difference observed in KAP across different education levels of the
      subjects regarding the risk of CVD (P-value = 0.332, 0.185, and 0.160,
      respectively). Conclusion: This study revealed that patients had good knowledge
      and attitude regarding CVD risk factors. Yet, the number of smokers is still
      quite high. Development of better public information system is essential for the
      well-being of the society.

PMID- 29657503
TI  - Phytochemical Constituents and Antimicrobial Activity of the Ethanol and
      Chloroform Crude Leaf Extracts of Spathiphyllum cannifolium (Dryand. ex Sims)
      Schott.
AB  - Context: The study investigated the medicinal properties of Spathiphyllum
      cannifolium (Dryand. ex Sims) Schott as a possible source of antimicrobial
      compounds. Materials and Methods: The phytochemical constituents were screened
      using qualitative methods and the antibacterial and antifungal activities were
      determined using agar well diffusion method. Statistical Analysis: One-way
      analysis of variance and Fisher's least significant difference test were used.
      Results: The phytochemical screening showed the presence of sterols, flavonoids,
      alkaloids, saponins, glycosides, and tannins in both ethanol and chloroform leaf
      extracts, but triterpenes were detected only in the ethanol leaf extract. The
      antimicrobial assay revealed that the chloroform leaf extract inhibited Candida
      albicans, Escherichia coli, Staphylococcus aureus, Bacillus subtilis, and
      Pseudomonas aeruginosa, whereas the ethanol leaf extract inhibited E. coli, S.
      aureus, and B. subtilis only. The ethanol and chloroform leaf extracts exhibited
      the highest zone of inhibition against B. subtilis. The antifungal assay showed
      that both the leaf extracts have no bioactivity against Aspergillus niger and C.
      albicans. Conclusions: Results suggest that chloroform is the better solvent for
      the extraction of antimicrobial compounds against the test organisms used in this
      study. Findings of this research will add new knowledge in advancing drug
      discovery and development in the Philippines.

PMID- 29657504
TI  - Safety Evaluation of Various Vector Repellents in Combination with Deltamethrin
      in Wistar Rats.
AB  - Background: Vector repellents are used globally to avoid insect bites and control
      transmission of diseases. It is important to ensure safety levels of these
      compounds, although they are noxious to insects. Vector repellents when used in
      combination are known to bring additional benefits in getting rid of the harmful
      insects. Unfortunately, the safety levels of various vector repellents such as
      Deet (N,N-diethyl-m-toluamide), Depa (N,N-diethyl phenylacetamide), and Deb (N,N
      diethylbenzamide) are not studied in combination with the widely used pyrethroid
      deltamethrin (Del). Materials and Methods: In this study, safety evaluation of
      various vector repellents by oral route in combination with Del was studied by
      assessing body weight and organ weight changes, hematological parameters, and
      biochemical parameters in Wistar rats. Results: The results revealed significant
      changes in liver marker enzymes in Del, Deb, Del + Depa, and Del + Deet groups.
      Urea levels were significantly altered after treatment with various repellents
      and in combination with Del, except Deb-alone group. Hematological and rest of
      the biochemical parameters were found to be unaltered in all the treatment
      groups. Significant changes in the liver weight were found in Deb, Depa, Deet,
      Del + Deb, and Del + Deet groups. Conclusions: Taken together, the overall
      results of this study indicate that single, high oral dose of various insect
      repellents did not show any additive toxicity.

PMID- 29657505
TI  - Knowledge and Attitude of Health-Care Professionals Toward Adverse Drug Reactions
      Reporting at King Saud Medical City.
AB  - Background: Health-care professionals across the globe are obligated to report
      adverse drug reactions (ADRs). The knowledge of ADRs and attitude of health-care
      professionals toward ADRs reporting is vital for patient safety. This study
      intends to investigate the knowledge of ADRs and attitude of health-care
      professionals toward ADRs reporting. Materials and Methods: A cross-sectional
      study using an anonymous questionnaire was conducted over a period of 3 months
      (September 2016 to November 2016) at King Saud Medical City, Riyadh, Saudi
      Arabia. This study included 399 questionnaires submitted by health-care
      professionals. Results: A total of 399 questionnaires were submitted by health
      care professionals, of which only 14.8% knew the term "ADR" and 55.1% of the
      respondents reported ADRs during their practice. A total of 93.8% of the
      respondents agreed that ADR reporting should be made mandatory for health-care
      professionals, and 94.5% agreed that it improves the patient safety. Conclusion:
      The findings generally indicate that health-care professionals in a tertiary care
      setting have low awareness regarding the term "ADR." Lack of pharmacovigilance
      training, amount of workload, and legal liabilities are the main causes of
      underreporting. More than half of the respondents agreed that ADR reporting
      eventually improves patient safety.

PMID- 29657506
TI  - In Vivo Evaluation of the Anticancer Activity of the Gemcitabine and Doxorubicin
      Combined in a Nanoemulsion.
AB  - Context: Doxorubicin (DOX) and gemcitabine (GEM) are anticancer drugs that were
      combined in a nanoemulsion (NE) to reduce their adverse side effects. Aim: To
      detect the antitumor activity of the combination formulas of GEM and DOX, loaded
      either in water (GEM+DOX-Sol) or in NEs (GEM-DOX combination/loaded NE
      [GEM+DOX/LNE]), in female Swiss albino mice inoculated with Ehrlich ascites
      carcinoma (EAC). Settings and Design: The anticancer assessment of the NE
      formulas was implemented in 200 mice, which were divided into 10 groups.
      Materials and Methods: It includes the detection of the change in body weight,
      analysis of the hematological and serum biochemical profiles, and study of the
      histopathologic alterations of the heart tissues. Statistical Analysis: One
      factor analysis of variance was used. Results: Mice treated with GEM + DOX/LNE,
      which have an z-average of 155.38+/-2.33nm and zeta potential of -38.5+/-1.3 mV,
      recorded a considerable improvement in the mean survival time (MST), which was 60
      days, as compared to the EAC control group, which has an MST of 28 days. It also
      restored the hematological and serum biochemical parameters toward normal values.
      Conclusions: The combination of GEM and DOX in NE has significantly diminished
      the cardiotoxicity of DOX and hematotoxicity of GEM while improving their
      antitumor properties.

PMID- 29657507
TI  - Initial Response of Human Bone Marrow-Derived Stem Cells after Contact with
      Ultrahigh-Molecular-Weight Polyethylene (UHMWPE) Material: An In Vitro Study on
      Cell Viability and Interleukin-6 Expression.
AB  - Introduction: Ultrahigh-molecular-weight polyethylene (UHMWPE) is a thermoplastic
      polymer useful in biomaterial applications, especially in orthopedic field. Yet,
      little is known concerning its initial effect on human bone marrow stem cells
      (hBMSCs) after implantation. Materials and Methods: A cytotoxicity analysis was
      performed with a 3-(4,5-dimethylthiazol 2-yl)-2,5-diphenyltetrazolium assay after
      24, 48, and 72h of incubation of hBMSC culture. Expression of interleukin-6 (IL
      6) was measured using enzyme-linked immunosorbent assay. Cell viability was
      measured with Inhibitory concentration 50% (IC50) formula. Results: All treatment
      groups showed a cell viability of >50% ranging from 78% to >100%. Lower
      expression of IL-6 of hBMSC compared to control group was found in 48h of
      incubation period. Conclusion: hBMSC showed high cell viability after initial
      contact with UHMWPE material. Modulation of IL-6 expression was present at the
      initial stage as a response to foreign material.

PMID- 29657509
TI  - A Tensor Statistical Model for Quantifying Dynamic Functional Connectivity.
AB  - Functional connectivity (FC) has been widely investigated in many imaging-based
      neuroscience and clinical studies. Since functional Magnetic Resonance Image
      (MRI) signal is just an indirect reflection of brain activity, it is difficult to
      accurately quantify the FC strength only based on signal correlation. To address
      this limitation, we propose a learning-based tensor model to derive high
      sensitivity and specificity connectome biomarkers at the individual level from
      resting-state fMRI images. First, we propose a learning-based approach to
      estimate the intrinsic functional connectivity. In addition to the low level
      region-to-region signal correlation, latent module-to-module connection is also
      estimated and used to provide high level heuristics for measuring connectivity
      strength. Furthermore, sparsity constraint is employed to automatically remove
      the spurious connections, thus alleviating the issue of searching for optimal
      threshold. Second, we integrate our learning-based approach with the sliding
      window technique to further reveal the dynamics of functional connectivity.
      Specifically, we stack the functional connectivity matrix within each sliding
      window and form a 3D tensor where the third dimension denotes for time. Then we
      obtain dynamic functional connectivity (dFC) for each individual subject by
      simultaneously estimating the within-sliding-window functional connectivity and
      characterizing the across-sliding-window temporal dynamics. Third, in order to
      enhance the robustness of the connectome patterns extracted from dFC, we extend
      the individual-based 3D tensors to a population-based 4D tensor (with the fourth
      dimension stands for the training subjects) and learn the statistics of
      connectome patterns via 4D tensor analysis. Since our 4D tensor model jointly (1)
      optimizes dFC for each training subject and (2) captures the principle connectome
      patterns, our statistical model gains more statistical power of representing new
      subject than current state-of-the-art methods which in contrast perform above two
      steps separately. We have applied our tensor statistical model to identify ASD
      (Autism Spectrum Disorder) by using the learned dFC patterns. Promising
      classification results have been achieved demonstrating high discrimination power
      and great potentials in computer assisted diagnosis of neuro-disorders.

PMID- 29657508
TI  - Hypnotic Effect of Red Cabbage (Brassica oleracea) on Pentobarbital-Induced Sleep
      in Mice.
AB  - Objective: The present study was performed to investigate the effect of
      hydroalcoholic extract of red cabbage and its fractions on sleeping behavior in
      mice. Materials and Methods: The extract and its fractions were injected to mice
      and sleep duration as well as sleep latency were recorded. Furthermore, toxicity
      of the extract was determined both in vivo and in vitro. Results: The extract
      increased sleep duration at doses of 50-200mg/kg (P < 0.001). This observed
      hypnotic effect was comparable to that of diazepam (3mg/kg) (P < 0.001 in
      comparison with control group). Ethyl acetate, n-butanol, and aqueous fractions
      could increase sleep duration (P < 0.001). The sleep latency was decreased by the
      extract (P < 0.001) and only ethyl acetate fraction (P < 0.001). LD50 value for
      red cabbage extract was 2.4g/kg. There was no toxic effect on viability of
      cultured neuronal cells (PC12). Rotarod test results showed that there were no
      significant differences between the extract groups and the control group.
      Conclusion: The results suggest that red cabbage potentiates pentobarbital
      hypnosis without any toxic effect. The main component(s) responsible for this
      effect is most likely to be intermediate polar agent(s) such as flavonoids, which
      are found in ethyl acetate fraction of this plant.

PMID- 29657510
TI  - A new sequence convergent to Euler-Mascheroni constant.
AB  - In this paper, we provide a new sequence converging to the Euler-Mascheroni
      constant. Finally, we establish some inequalities for the Euler-Mascheroni
      constant by the new sequence.

PMID- 29657511
TI  - An upper bound for the Z-spectral radius of adjacency tensors.
AB  - Let [Formula: see text] be a k-uniform hypergraph on n vertices with degree
      sequence [Formula: see text]. In this paper, in terms of degree [Formula: see
      text], we give a new upper bound for the Z-spectral radius of the adjacency
      tensor of [Formula: see text]. Some examples are given to show the efficiency of
      the bound.

PMID- 29657512
TI  - Dual Decomposed Learning with Factorwise Oracles for Structural SVMs of Large
      Output Domain.
AB  - Many applications of machine learning involve structured outputs with large
      domains, where learning of a structured predictor is prohibitive due to
      repetitive calls to an expensive inference oracle. In this work, we show that by
      decomposing training of a Structural Support Vector Machine (SVM) into a series
      of multiclass SVM problems connected through messages, one can replace an
      expensive structured oracle with Factorwise Maximization Oracles (FMOs) that
      allow efficient implementation of complexity sublinear to the factor domain. A
      Greedy Direction Method of Multiplier (GDMM) algorithm is then proposed to
      exploit the sparsity of messages while guarantees convergence to epsilon sub
      optimality after O(log(1/epsilon)) passes of FMOs over every factor. We conduct
      experiments on chain-structured and fully-connected problems of large output
      domains, where the proposed approach is orders-of-magnitude faster than current
      state-of-the-art algorithms for training Structural SVMs.

PMID- 29657513
TI  - Regularized Modal Regression with Applications in Cognitive Impairment
      Prediction.
AB  - Linear regression models have been successfully used to function estimation and
      model selection in high-dimensional data analysis. However, most existing methods
      are built on least squares with the mean square error (MSE) criterion, which are
      sensitive to outliers and their performance may be degraded for heavy-tailed
      noise. In this paper, we go beyond this criterion by investigating the
      regularized modal regression from a statistical learning viewpoint. A new
      regularized modal regression model is proposed for estimation and variable
      selection, which is robust to outliers, heavy-tailed noise, and skewed noise. On
      the theoretical side, we establish the approximation estimate for learning the
      conditional mode function, the sparsity analysis for variable selection, and the
      robustness characterization. On the application side, we applied our model to
      successfully improve the cognitive impairment prediction using the Alzheimer's
      Disease Neuroimaging Initiative (ADNI) cohort data.

PMID- 29657514
TI  - Navigating Limited and Uncertain Access to Subsidized Housing After Prison.
AB  - An emerging literature has documented the challenges that formerly incarcerated
      individuals face in securing stable housing. Given the increasingly unaffordable
      rental market, rental subsidies represent an important and understudied source of
      stable housing for this population. The existing literature has described
      substantial discretion and a varied policy landscape that determine former
      prisoners' access to housing subsidies, or subsidized housing spaces that are
      leased to members of their social and family networks. Less is known about how
      former prisoners themselves interpret and navigate this limited and uncertain
      access to subsidized housing. Drawing on data from repeated qualitative
      interviews with 44 former prisoners, we describe the creative and often labor
      intensive strategies that participants employed to navigate discretion and better
      position themselves for subsidized housing that was in high demand, but also
      largely out of reach. Our findings also illustrate the potential costs associated
      with these strategies for both participants and members of their social and
      family networks.

PMID- 29657515
TI  - Trauma-informed Temporary Assistance for Needy Families (TANF): A Randomized
      Controlled Trial with a Two-Generation Impact.
AB  - Temporary Assistance for Needy Families (TANF) has limited success in building
      self-sufficiency, and rarely addresses exposure to trauma as a barrier to
      employment. The objective of the Building Wealth and Health Network randomized
      controlled trial was to test effectiveness of financial empowerment combined with
      trauma-informed peer support against standard TANF programming. Through the
      method of single-blind randomization we assigned 103 caregivers of children under
      age six into three groups: control (standard TANF programming), partial (28-weeks
      financial education), and full (same as partial with simultaneous 28-weeks of
      trauma-informed peer support). Participants completed baseline and follow-up
      surveys every 3 months over 15 months. Group response rates were equivalent
      throughout. With mixed effects analysis we compared post-program outcomes at
      months 9, 12, and 15 to baseline. We modeled the impact of amount of
      participation in group classes on participant outcomes. Despite high exposure to
      trauma and adversity results demonstrate that, compared to the other groups,
      caregivers in the full intervention reported improved self-efficacy and
      depressive symptoms, and reduced economic hardship. Unlike the intervention
      groups, the control group reported increased developmental risk among their
      children. Although the control group showed higher levels of employment, the full
      intervention group reported greater earnings. The partial intervention group
      showed little to no differences compared with the control group. We conclude that
      financial empowerment education with trauma-informed peer support is more
      effective than standard TANF programming at improving behavioral health, reducing
      hardship, and increasing income. Policymakers may consider adapting TANF to
      include trauma-informed programming.

PMID- 29657516
TI  - Somewhere to be permanent for a minute: Time and space perceptions of older adult
      men experiencing chronic homelessness in Detroit.
AB  - Within the landscape of postwar era Detroit, space is vast, but places are hard
      to find. As people tumble down the side of Maslow's pyramid into abject
      homelessness, they attempt to anchor themselves in locations that suspend the
      otherwise situational free fall. This article analyzes how time and space are
      perceived by people experiencing chronic homelessness and how those individual
      perceptions are informed by the objective time and space urban environment. We
      conducted our community-based participatory research into the experiences of
      chronic homelessness both from perspectives of chronically homeless older adult
      men and from front-line service providers. Themes that emerged are as follows:
      (1) temporary permanence, (2) permanent temporariness, and (3) lostness. The
      article concludes with policy implications regarding the procedures for measuring
      the extent of homelessness and the needs of those who live it.

PMID- 29657517
TI  - Salivary point-of-care technology.

PMID- 29657518
TI  - Influence of light activation of simplified adhesives on the shear bond strength
      of resin cements to a leucite-reinforced ceramic.
AB  - Objective: This study aims to evaluate the influence of the light activation of
      simplified adhesives on the shear bond strength of resin cements to a glass
      ceramic. Three factors were evaluated: (1) cement in two levels (light cured and
      dual cured); (2) adhesive in two levels (Single Bond 2 and Single Bond
      Universal), and (3) light activation in two levels (yes or no). Materials and
      Methods: Thirty-two 1-mm thick slices of a leucite-reinforced glass-ceramic (IPS
      Empress CAD) were divided into eight groups according to adhesive (Single Bond 2
      or Single Bond Universal), cement (AllCem Veneer or AllCem), and light activation
      of the adhesive before application of the cement (yes or no). Ceramic surfaces
      were etched for 60 s with 5% hydrofluoric acid, and adhesives were applied. Four
      cement cylinders were made over each ceramic slice (n = 16) and then submitted to
      shear bond strength tests. Statistical Analysis: Data were analyzed with three
      way ANOVA and Tukey (alpha = 0.05). Results: There were significant differences
      between adhesives (P < 0.0001) and no differences between cements (P = 0.0763)
      and light activation (P = 0.4385). No interaction effect occurred (P = 0.05).
      Single Bond 2 showed higher bond strength than Single Bond Universal.
      Conclusions: The light activation of the adhesive before the application of the
      resin cement did not influence the bond strength.

PMID- 29657519
TI  - Antibacterial effectiveness of probiotic-based experimental mouthwash against
      cariogenic pathogen: An in vitro study.
AB  - Objectives: The aim of this study is to assess the antibacterial effectiveness of
      probiotic-experimental-based mouthwash (MW) against Streptococcus mutans in
      vitro. Materials and Methods: Antimicrobial screening of two active additives
      (probiotic-zamzam) was tested against S. mutans using disc diffusion method. A
      total of three MWs; (1) an experimental MW base formula, (2) an experimental MW
      base formula with the two active additives, and (3) commercial MW (hexitol), were
      evaluated against S. mutans by well diffusion method after 24 h and 72 h storage
      period. The survival profile of probiotic strain in the experimental MW was
      determined using colony counting method as well as the pH changes at three
      intervals. Statistical analysis was performed using one-way ANOVA and t-test to
      compare the inhibition zone diameter. Results: For active additives, probiotic
      strain exhibited higher mean inhibition zones values than zamzam water against S.
      mutans. Regarding the inhibition zones for the three tested MWs, the experimental
      MW showed significant increase in the inhibition zone after 72 h, while there was
      insignificant change with commercial MW. For probiotic count in MW, there was
      insignificant change in bacterial count after 24 h, and significant decrease
      after 15 days, followed by insignificant change after 30 days. For the pH values
      of the experimental MW, a statistically insignificant change was found after 24
      h, significant decrease after 15 days and insignificant change after 30 days.
      Conclusions: The probiotic-zamzam experimental MW was effective in reducing S.
      mutans. Zamzam water could be considered as prebiotic ingredient. Therefore, the
      probiotic-zamzam MW has a potential therapeutic value.

PMID- 29657520
TI  - Dental caries prevalence and its association with fluoride level in drinking
      water in Sana'a, Yemen.
AB  - Objectives: Dental caries is the most prevalent chronic condition affecting
      schoolchildren worldwide. This study is aimed to assess the prevalence of dental
      caries among schoolchildren in urban and rural districts of Sana'a governorate,
      Yemen, and to investigate the correlation between caries experience and level of
      fluoride in drinking water, age, gender, and residence. Materials and Methods:
      This school-based survey involved 17,599 schoolchildren (aged 6-12 years), of
      whom 9623 were boys and 7976 were girls. We used decay-missing-filled teeth/decay
      filled teeth (DMFT/dft) indices to evaluate dental caries experience. In
      addition, fluoride concentration in drinking water was investigated. Results:
      Around 67.6% of children had dental caries. Children residing in urban districts
      had significantly higher mean scores of DMFT/dft than those in rural areas (P <
      0.05). A significant negative correlation between caries experience and fluoride
      level was found (P < 0.05), with the lowest dft/DMFT scores at the optimum
      fluoride level of 0.61-2 ppm and the highest at two extremes, 0.0-0.4 ppm and >2
      ppm. Conclusion: This survey found a very high prevalence of caries among
      schoolchildren in Yemen. There was also an inverse relation between dental caries
      experience and fluoride levels.

PMID- 29657521
TI  - Volumetric analysis of hand, reciprocating and rotary instrumentation techniques
      in primary molars using spiral computed tomography: An in vitro comparative
      study.
AB  - Objective: This present study was conducted to analyze the volumetric change in
      the root canal space and instrumentation time between hand files, hand files in
      reciprocating motion, and three rotary files in primary molars. Materials and
      Methods: One hundred primary mandibular molars were randomly allotted to one of
      the five groups. Instrumentation was done using Group I; nickel-titanium (Ni-Ti)
      hand file, Group II; Ni-Ti hand files in reciprocating motion, Group III; Race
      rotary files, Group IV; prodesign pediatric rotary files, and Group V; ProTaper
      rotary files. The mean volumetric changes were assessed using pre- and post
      operative spiral computed tomography scans. Instrumentation time was recorded.
      Statistical analysis to access intergroup comparison for mean canal volume and
      instrumentation time was done using Bonferroni-adjusted Mann-Whitney test and
      Mann-Whitney test, respectively. Results: Intergroup comparison of mean canal
      volume showed statistically significant difference between Groups II versus IV,
      Groups III versus V, and Groups IV versus V. Intergroup comparison of mean
      instrumentation time showed statistically significant difference among all the
      groups except Groups IV versus V. Conclusion: Among the various instrumentation
      techniques available, rotary instrumentation is the considered to be the better
      instrumentation technique for canal preparation in primary teeth.

PMID- 29657522
TI  - Cariogenicity induced by commercial carbonated beverages in an experimental
      biofilm-caries model.
AB  - Objectives: Frequent consumption of sugars-containing carbonated beverages has
      been associated with caries, but the consequences on the dental biofilm remain
      unclear. The aim was to evaluate the effect of commercial carbonated beverages
      and their sugar-free version on enamel and dentine demineralization and on the
      cariogenic properties of Streptococcus mutans biofilms. Materials and Methods:
      Biofilms of S. mutans UA159 were grown on enamel and dentin slabs and exposed 3
      times/day for 5 min, to a commercial cola or orange-flavored carbonated beverage
      or to their sugar-free version. Biofilms/slabs were recovered to assess biomass,
      viable microorganisms, protein content and polysaccharides. Demineralization was
      estimated by the variation of Knoop surface microhardness. Results: Exposures to
      the biofilm with sugars-containing carbonated beverages resulted in similar
      biomass, viable microorganisms, proteins, and polysaccharides than sucrose (P <
      0.05). The sugar-free cola and orange-flavored drink showed lower effect on the
      biofilm, as compared with sucrose or their sugared version (P < 0.05). All of the
      products tested, included the sugar-free, showed higher demineralization than the
      negative control (P < 0.05). Conclusions: Sugars-containing carbonated beverages
      enhance cariogenic activity of S. mutans biofilms, comparable with sucrose. Sugar
      free carbonated beverages also have a high demineralizing potential, without
      affecting biofilm properties.

PMID- 29657523
TI  - Comparison of osteoclastogenesis and local invasiveness of ameloblastoma and
      keratocystic odontogenic tumor.
AB  - Objectives: The aim of this study was to compare the expression of receptor
      activated nuclear factor kappa B (RANK) with its ligand (RANKL) and matrix
      metalloproteinase-2 (MMP2) in solid/multicystic ameloblastomas (ABs) and
      keratocystic odontogenic tumors (KOTs). Materials and Methods: The expression of
      MMP2, RANK, and RANKL molecules was evaluated in 13 ABs and 14 KOTs by
      immunohistochemistry. The expressions were calculated in the odontogenic
      epithelial cells as well as the stromal cells. Results: Odontogenic epithelia of
      AB expressed MMP2, RANK, and RANKL significantly higher than that of KOTs (P <
      0.05). The expression of MMP2, RANK, and RANKL was highest in plexiform subtype
      (79.9%, 81.08%, and 65.1%, respectively). KOTs without daughter epithelia nests
      expressed both MMP2 and RANK the least (56.06% and 47.5%, respectively). Stromal
      cells, on the other hand, expressed similar MMP2 pattern in odontogenic epithelia
      of both AB and KOT. RANKL was expressed weaker in the stromal cells of both
      lesions. Conclusion: Invasive biological and osteolytic behaviors of both lesions
      were evaluated in this study. It was found to be more in AB than keratocystic
      odontogenic. A significant expression of MMP2, RANK, and RANKL in both KOTs
      associated with microcyst and plexiform type AB as well.

PMID- 29657524
TI  - Conceptual knowledge of oral health among school teachers in South India, India.
AB  - Objective: To measure conceptual oral health knowledge among school teachers
      using comprehensive measure of oral health knowledge (CMOHK) instrument.
      Materials and Methods: A total of 240 school teachers drawn through cluster
      random sampling from across Sullia taluk. Conceptual knowledge was assessed using
      Comprehensive measure of oral health knowledge questionnaire. Oral health status
      was recorded on a World Health Organization oral health assessment Proforma.
      Results: Overall distribution of CMOHK scores revealed that 106(44%) subjects had
      good conceptual oral health knowledge, 81(33.7%) subjects had fair and 53(22%)
      subjects were categorized under poor conceptual knowledge respectively.
      Statistically significant difference was observed for mean scores for conceptual
      knowledge in relation to gender (12.8v/s 15.3), in terms of type of school
      teachers (14.4 v/s 11.2) and in relation to age of the subjects. Primary school
      teachers exhibited a consistently better CMOHK scores 0.003(0.001-0.011) compared
      to their high school counterparts 0.003(0.001-0.012). Conclusion: The mean CMOHK
      score of this group was 12.5+/-1.3 and is considered to be fair. There is an
      inverse association between age, educational levels and income in relation to
      CMOHK scores.

PMID- 29657525
TI  - Effect of different surface finishing/polishing procedures on color stability of
      esthetic restorative materials: A spectrophotometric evaluation.
AB  - Objective: To evaluate the color stability of different esthetic restorative
      materials after surface finishing/polishing with different procedures. Materials
      and Methods: All materials were polymerized into silicone rubber rings to obtain
      specimens identical in size. Samples were randomly assigned into four groups (10
      specimens of each composite for each group), and they were finished with
      different procedures: Control group (Group 1), three or two polishers
      interspersed with diamond grit (Groups 3 and 2, respectively), and one tungsten
      carbide bur + one polisher interspersed with diamond grit (Group 4). After
      staining process in coffee, a colorimetric evaluation according to the CIE L*a*b*
      system was performed by a blind trained operator at 7, 14, 21, and 28 days.
      Shapiro-Wilk test and Kruskal-Wallis analysis of variance were applied to assess
      significant differences among restorative materials. Means of the different
      polishing/finishing groups were compared with Scheffe's multiple comparison test
      at the 0.05 level of significance. Results: In control group, significant lower
      discolorations were recorded for Essentia, Admira Fusion, and Estelite. After
      finishing, Filtek Supreme XTE and Ceram.X Universal showed a significantly lower
      degree of staining. The finishing technique used for Group 4 produced higher
      color changes. Conclusions: Tungsten carbide burs produced the higher color
      variations; after finishing, the nanofilled composites showed lower discoloration
      than nanohybrid ones, and the time of exposure to the staining agent and the
      polishing/finishing technique influenced the color change.

PMID- 29657526
TI  - Comparative abrasive wear resistance and surface analysis of dental resin-based
      materials.
AB  - Objective: The objective of this study was to assess the surface properties
      (microhardness and wear resistance) of various composites and compomer materials.
      In addition, the methodologies used for assessing wear resistance were compared.
      Materials and Methods: This study was conducted using restorative material
      (Filtek Z250, Filtek Z350, QuiXfil, SureFil SDR, and Dyract XP) to assess wear
      resistance. A custom-made toothbrush simulator was employed for wear testing.
      Before and after wear resistance, structural, surface, and physical properties
      were assessed using various techniques. Results: Structural changes and mass loss
      were observed after treatment, whereas no significant difference in terms of
      microhardness was observed. The correlation between atomic force microscopy (AFM)
      and profilometer and between wear resistance and filler volume was highly
      significant. The correlation between wear resistance and microhardness were
      insignificant. Conclusions: The AFM presented higher precision compared to
      optical profilometers at a nanoscale level, but both methods can be used in
      tandem for a more detailed and precise roughness analysis.

PMID- 29657527
TI  - Comparative evaluation of salivary malondialdehyde levels as a marker of lipid
      peroxidation in early childhood caries.
AB  - Objective: The aim of this study was to evaluate the association between lipid
      peroxidation and dental caries in children with ECC by estimating the levels of
      MDA in saliva of children. Materials and Methods: A total of 150 children were
      selected; 75 children with ECC and 75 children without caries (non-ECC). Saliva
      samples were collected and centrifuged at 12,000 rpm for 24 min at 4 degrees C to
      obtain a supernatant. MDA levels were estimated by Buege and Aust method by using
      thiobarbituric acid. The data obtained were analyzed by Student's t-test to
      compare MDA levels between the groups. Results: MDA levels were higher in
      children with ECC. There was no statistically significant difference between
      children with ECC and without ECC (non-ECC). Conclusion: MDA levels were slightly
      higher in children with ECC, indicating the role of lipid peroxidation in the
      carious process.

PMID- 29657528
TI  - Digital versus conventional techniques for pattern fabrication of implant
      supported frameworks.
AB  - Objective: The aim of this experimental study was to compare retention of
      frameworks cast from wax patterns fabricated by three different methods.
      Materials and Methods: Thirty-six implant analogs connected to one-piece
      abutments were divided randomly into three groups according to the wax pattern
      fabrication method (n = 12). Computer-aided design/computer-aided manufacturing
      (CAD/CAM) milling machine, three-dimensional printer, and conventional technique
      were used for fabrication of waxing patterns. All laboratory procedures were
      performed by an expert-reliable technician to eliminate intra-operator bias. The
      wax patterns were cast, finished, and seated on related abutment analogs. The
      number of adjustment times was recorded and analyzed by Kruskal-Wallis test.
      Frameworks were cemented on the corresponding analogs with zinc phosphate cement
      and tensile resistance test was used to measure retention value. Statistical
      Analysis Used: One-way analysis of variance (ANOVA) and post hoc Tukey tests were
      used for statistical analysis. Level of significance was set at P < 0.05.
      Results: The mean retentive values of 680.36 +/- 21.93 N, 440.48 +/- 85.98 N, and
      407.23 +/- 67.48 N were recorded for CAD/CAM, rapid prototyping, and conventional
      group, respectively. One-way ANOVA test revealed significant differences among
      the three groups (P < 0.001). The post hoc Tukey test showed significantly higher
      retention for CAD/CAM group (P < 0.001), while there was no significant
      difference between the two other groups (P = 0.54). CAD/CAM group required
      significantly more adjustments (P < 0.001). Conclusions: CAD/CAM-fabricated wax
      patterns showed significantly higher retention for implant-supported cement
      retained frameworks; this could be a valuable help when there are limitations in
      the retention of single-unit implant restorations.

PMID- 29657529
TI  - Impact of electro-neuro-feedback on postoperative outcome of impacted lower third
      molar surgery.
AB  - Objective: The purpose of this study was to evaluate the impact of a treatment
      with electro-neuro-feedback (ENF), a portable transcutaneous electrical nerve
      stimulation (TENS) device, on the clinical outcome and inflammatory biochemical
      parameters related to the impacted lower third molar surgery. Materials and
      Methods: A randomized, split-mouth, and single-blind study was conducted on 32
      patients requiring lower third molars extractions and referred to the Oral
      Surgery Unit of the School of Dentistry of the University of Messina. Every
      patient underwent surgical removal of both lower third molars. The first
      extraction included a placebo (electrodes placement with turned-off device)
      treatment following the surgery, while the second had the ENF used next to the
      avulsion and the following days. Clinical parameters were collected 4 days
      before, immediately after, 2, 4, and 7 days after the surgical procedure.
      Biochemical parameters were obtained 1 day before the surgical removal and 7 days
      after. Data were processed using Wilcoxon-Mann-Whitney test, with significance
      being set at P < 0.05. Results: Clinical outcome parameters showed a significant
      improvement after the ENF treatment, while considered inflammatory markers
      expressed different patterns. Conclusions: ENF, a reliable portable TENS device,
      has demonstrated to be a useful tool in the managing of the postsurgical phases,
      reducing edema, pain, and consequent pain-killers consumption.

PMID- 29657530
TI  - Increase the glyde path diameter improves the centering ability of F6 Skytaper.
AB  - Objective: The aim of this study was to assess the impact of glide path
      preparation, performed with PathGlider 0.15 (Komet Brasseler GmbH & Co., Lemgo,
      Germany) and PathGlider 0.20 (Komet Brasseler GmbH & Co., Lemgo, Germany), on the
      centering ability of 25-size F6 Skytaper in J-shape simulated root canals,
      compared with no glide path executed. Materials and Methods: Sixty J-shaped ISO
      15 0.02 taper endo training blocks (Dentsply Maillefer) were assigned to three
      groups (n = 20 for each group). Photographic images were taken on endoblocks
      before and after shaping procedures. After superimposition, the software AutoCAD
      2013 (Autodesk Inc., San Rafael, USA) was used for record the centering and
      shaping ability at 9 different levels from the apex. Results: Shaping procedures
      including the using of PathGlider 0.20 resulted in a lower amount of resin
      removed and in a clear improvement of centering ability of the Skytaper 0.25 at
      almost all reference point levels. Conclusions: Within the limitations of this
      study, it could be concluded that the glide path procedure, performed with the
      PathGlider 0.20 before the shaping with 25-size F6 Skytaper, might determine a
      lower amount of resin removed and a better centering ability compared with the
      groups without glide path procedure and those treated with PathGlider 0.15.

PMID- 29657532
TI  - Physicochemical and microscopic characterization of implant-abutment joints.
AB  - Objective: The purpose of this study was to investigate Morse taper implant
      abutment joints by chemical, mechanical, and microscopic analysis. Materials and
      Methods: Surfaces of 10 Morse taper implants and the correlated abutments were
      inspected by field emission gun-scanning electron microscopy (FEG-SEM) before
      connection. The implant-abutment connections were tightened at 32 Ncm. For
      microgap evaluation by FEG-SEM, the systems were embedded in epoxy resin and
      cross-sectioned at a perpendicular plane of the implant-abutment joint.
      Furthermore, nanoindentation tests and chemical analysis were performed at the
      implant-abutment joints. Statistics: Results were statistically analyzed via one
      way analysis of variance, with a significance level of P < 0.05. Results: Defects
      were noticed on different areas of the abutment surfaces. The minimum and maximum
      size of microgaps ranged from 0.5 MUm up to 5.6 MUm. Furthermore, defects were
      detected throughout the implant-abutment joint that can, ultimately, affect the
      microgap size after connection. Nanoindentation tests revealed a higher hardness
      (4.2 +/- 0.4 GPa) for abutment composed of Ti6Al4V alloy when compared to implant
      composed of commercially pure Grade 4 titanium (3.2 +/- 0.4 GPa). Conclusions:
      Surface defects produced during the machining of both implants and abutments can
      increase the size of microgaps and promote a misfit of implant-abutment joints.
      In addition, the mismatch in mechanical properties between abutment and implant
      can promote the wear of surfaces, affecting the size of microgaps and
      consequently the performance of the joints during mastication.

PMID- 29657531
TI  - Antimicrobial efficacy of 2.5% sodium hypochlorite, 2% chlorhexidine, and
      ozonated water as irrigants in mesiobuccal root canals with severe curvature of
      mandibular molars.
AB  - Objective: The aim of this study is to evaluate the antimicrobial efficacy of
      2.5% sodium hypochlorite, 2% chlorhexidine, and ozonated water on biofilms of
      Enterococcus faecalis, Streptococcus mutans, and Candida albicans in mesiobuccal
      root canals with severe curvature of mandibular molars. Materials and Methods:
      This was an experimental ex vivo study in microbiologic laboratory. Sixty
      mesiobuccal root canals with severe curvature of mandibular molars were
      contaminated with standard strains of E. faecalis, S. mutans, and C. albicans.
      The specimens were randomly divided into four groups (n = 15) according to
      irrigating solution: SH: 2.5% sodium hypochlorite; CH: 2% chlorhexidine; O3:
      ozonated water; and control: double-distilled water. The mesiobuccal root canals
      of all groups were instrumented with the WaveOne Gold Primary reciprocating
      system. Three cycles of instrumentation with three short in-and-out brushing
      motions were performed: (1) in the coronal third, (2) in the middle third, and
      (3) in the apical third of the canal. A ProGlider file was used before the first
      cycle. Statistical Analysis: Statistical analysis was performed using one-way
      analysis of variance followed by Tukey's multiple comparison test. Samples were
      collected for viable bacterial counts before and after instrumentation. Results:
      All groups showed significant biofilm reduction after irrigation (P < 0.01).
      After instrumentation, sodium hypochlorite (98.07%), chlorhexidine (98.31%), and
      ozonated water (98.02%) produced a significantly reduction in bacterial counts
      compared with double-distilled water (control, 72.98%) (P < 0.01). Conclusion:
      All irrigants tested in this study showed similar antimicrobial activity. Thus,
      ozonated water may be an option for microbial reduction in the root canal system.

PMID- 29657534
TI  - Quality of life of dentists.
AB  - Objective: An important determinant of job satisfaction and life fulfillment is
      the quality of life (QOL) of the individuals working in a particular field.
      Currently, in the United Arab Emirates (UAE), there is limited research
      pertaining to the QOL of dentists. The main objective of this study was to assess
      QOL of dentists in the UAE. Materials and Methods: The World Health Organization
      (WHO) QOL-BREF questionnaire (the World Health Organization abbreviated
      instrument for QOL assessment), which assesses QOL in physical, psychological,
      social, and environmental domains, was found to be a suitable instrument for use.
      A total of 290 questionnaires were distributed to general dental practitioners
      and specialists working in the private sector. The response rate was 46%. The
      completed questionnaires were coded and analyzed using the SPSS IBM software
      version 21. Results: QOL of specialists was significantly better than general
      practitioners (GPs) on all domains of the WHOQOL-BREF (P < 0.05). Married
      dentists had better QOL than singles on the social and environmental domains.
      Furthermore, specialists reported significantly better QOL compared to GPs after
      adjustment for sex, age, and marital status (P < 0.05) in the psychosocial and
      environmental domains. Conclusions: Among dentists who work in the UAE, QOL can
      be affected by several factors, one of them being whether dentist is a GP or a
      specialist.

PMID- 29657533
TI  - Effect of 0.12% chlorhexidine and zinc nanoparticles on the microshear bond
      strength of dentin with a fifth-generation adhesive.
AB  - Objective: In this study, we compared the effects of 0.12% chlorhexidine (CHX)
      and nano zinc oxide (NZO) on the microshear bond strength of dentin with a fifth
      generation adhesive after acid etching. Materials and Methods: Forty molar teeth
      were randomly divided into four main groups based on dentin surface treatment
      technique (a) control (single bond 2); (b) NZO; (c) CHX; and (d) NZO + CHX. In
      each group, half of the samples underwent thermocycling, with no thermocycling in
      the other half. Then, failure mode was evaluated under a stereomicroscope.
      Statistical analysis was performed using t-test, two-way ANOVA, and Chi-squared
      test. Results: The mean microshear bond strength of the groups without
      thermocycling was more than that of the groups with thermocycling, but there were
      no statistically significant differences between the groups with and without
      thermocycling in pair-wise comparisons. Conclusion: Pretreatment with NZO and CHX
      separately and simultaneously had no effect on the microshear bond strength of a
      fifth-generation adhesive.

PMID- 29657535
TI  - Effect of heat polymerization conditions and microwave on the flexural strength
      of polymethyl methacrylate.
AB  - Objective: The objective of this study is the effect of different heat
      polymerization conditions on the strength of polymethyl methacrylate (PMMA) resin
      base is unknown. Distinguishing one method that provides improved mechanical
      properties may be beneficial to the clinical success of complete and partial
      dentures and overdentures. The purpose of this study was to evaluate the effect
      of different polymerization methods on the flexural strength of a dental PMMA
      resin. Materials and Methods: Forty PMMA specimens (64 mm * 10 mm * 4 mm) were
      prepared with 4 different polymerization methods (n = 10); heat polymerization at
      74 degrees C for 9 h, at 100 degrees C for 40 min, and with 620 kPa pressure at
      100 degrees C for 20 min. The remaining group of specimens was microwave
      polymerized at 180 W for 6 min. All specimens were thermocycled at 5 degrees C
      and 55 degrees C for 5000 times. Three-point flexure test was used to measure the
      flexural strength of specimens. One-way ANOVA and Tukey Honestly Significant
      Difference were applied to analyze the differences in flexural strengths (alpha =
      0.05). Results: The flexural strength of heat-polymerized groups was similar. The
      flexural strength of microwave polymerized group was significantly different and
      lower than the other groups (P < 0.05). Conclusion: Polymerizing conventional
      heat-polymerizing PMMA resin with microwave energy resulted in a significant
      decrease in flexural strength. The results of this study suggest that clinicians
      may benefit from using heat polymerization when processing PMMA denture bases
      instead of microvawe polymerization when tested brand is used.

PMID- 29657536
TI  - The relationship between tooth loss, body mass index, and hypertension in
      postmenopausal female.
AB  - Objective: This study aimed to investigate the relationship between tooth loss
      and the level of blood pressure with the hypothesis that tooth loss is associated
      with the increase of hypertension in postmenopausal women. Materials and Methods:
      Sixty postmenopausal female patients aged 51-68 years were included in the study
      to assess the relationship between tooth loss and the level of blood pressure.
      The information including sociodemographics, last menstruation period,
      hypertension history, and the duration of having tooth loss was recorded. Blood
      pressure was measured using sphygmomanometer and the number of tooth loss was
      determined. Results: The results showed a more significant tooth loss in
      hypertension (median: 23 + 4; interquartile range [IQR]: 6) compared to the
      normotension postmenopausal women (median: 18 + 6; IQR: 12; P < 0.05).
      Furthermore, obese patients had more tooth loss (median: 23 + 5; IQR: 8) than the
      overweight patients (median: 19 + 8; IQR: 8). Conclusion: Tooth loss is
      associated with the increase of hypertension in postmenopausal women which may
      have a role in the development of vascular diseases.

PMID- 29657537
TI  - Analysis of vertical marginal discrepancy in feldspathic porcelain crowns
      manufactured with different CAD/CAM systems: Closed and open.
AB  - Objective: The objective of this study is to compare the marginal adaptation of
      feldspathic porcelain crowns using two computer-aided design/computer-aided
      manufacturing systems, one of them is open and the other is closed. Materials and
      Methods: Twenty identical titanium abutments were divided into two groups: open
      system (OS), where ceramic crowns were created using varied equipment and
      software, and closed system (CS), where ceramic crowns were created using the
      CEREC system. Through optical microscopy analysis, we assess the marginal
      adaptation of the prosthetic interfaces. The data were subjected to the
      distribution of normality and variance. The t-test was used for the analysis of
      the comparison factor between the groups, and the one-way ANOVA was used to
      compare the variance of crown analysis regions within the group. A significance
      level of 5% was considered for the analyses. Results: There was a significant
      difference between the systems (P = 0.007), with the CS group having the higher
      mean (23.75 MUm +/- 3.05) of marginal discrepancy when compared to the open group
      (17.94 MUm +/- 4.77). Furthermore, there were no differences in marginal
      discrepancy between the different points between the groups (P >= 0.05).
      Conclusions: The studied groups presented results within the requirements set out
      in the literature. However, the OS used presented better results in marginal
      adaptation.

PMID- 29657538
TI  - Impact of malocclusion severity on oral health-related quality of life in an
      Iranian young adult population.
AB  - Objective: This study aimed to assess the relationship between malocclusion
      severity and oral health-related quality of life (QoL) of 18 to 25-year-old
      Iranians who sought orthodontic treatment. Materials and Methods: A total of 126
      patients between 18 and 25 years attending some private orthodontic clinics
      answered the oral health impact profile-14 (OHIP-14) and a demographic
      questionnaire. Two calibrated orthodontists recorded the Index of Orthodontic
      Treatment Need-Dental Health Component (IOTN-DHC) determining the severity of
      malocclusion (Kappa = 0.8). The IOTN-Aesthetic Component (IOTN-AC) was reported
      by patients for assessing the perception of their esthetic severity of
      malocclusion. Logistic regression analysis was used. Level of significance was
      set at alpha = 0.05. Results: The mean score of OHIP-14 was 20.87 +/- 8.6. The
      frequency of patients with no/slight, borderline, and definite need for
      orthodontic treatment was determined as 13.4%, 23.8%, and 62.7%, respectively, by
      IOTN-DHC. There were significant correlations between borderline or definite need
      treatment and OHIP-14 overall score (P < 0.05). Patients with borderline and
      definite need for orthodontic treatment had 5 and 21 times lower QoL,
      respectively, than those with a slight need for orthodontic treatment. Based on
      IOTN-AC, 50.8% of the patients mentioned slight or no need based on IOTN-AC. No
      significant association was noted between IOTN-AC and OHIP-14 overall scores.
      Conclusions: The results showed negative impact of malocclusion severity on the
      QoL. This study highlighted the importance of individual assessment of
      orthodontic patients.

PMID- 29657539
TI  - Cone-beam computed tomography in the assessment of periapical lesions in
      endodontically treated teeth.
AB  - Objective: This study aimed to evaluate the relationship between the quality of
      the coronal restoration and the root canal filling on the periapical status of
      endodontically treated teeth using CBCT. Materials and Methods: CBCT data were
      obtained from the records of patients who deny any dental treatment in the 2
      years prior to the CBCT examination. CBCT images (90 kVp and 7 mA, exposure time
      of 23 s, and a voxel size of 0.2 mm, with a field of view of 13 cm * 13 cm) of
      1011 endodontically treated teeth were observed. A score was given to the quality
      of the root filling and the quality of the coronal restoration. Statistical
      Analysis Used: Data were statistically analyzed to correlate the periapical
      status with gender, dental group. and quality of endodontic treatment and
      restoration (Chi-square test with a significance level of P < 0.001). Results:
      Absence of periapical periodontitis was found in 54.9% of the cases. The
      periapical outcome was not related to gender or dental group (P > 0.05). A
      statistically significant factor (Chi-square test, P < 0.0001) resulted when
      different qualities of sealing were compared. Conclusions: CBCT showed that high
      quality root canal treatments followed by an adequate coronal sealing restoration
      avoid the presence of periapical periodontitis in time.

PMID- 29657540
TI  - Relationship between Expanded Disability Status Scale scores and the presence of
      temporomandibular disorders in patients with multiple sclerosis.
AB  - Objectives: The objectives of this study were to assess the prevalence of
      temporomandibular disorders (TMDs) in patients with relapsing-remitting multiple
      sclerosis (MS) and to investigate whether an association exists between the
      presence of TMD symptoms and the degree of MS-related disability. Materials and
      Methods: In all, 120 individuals were evaluated: 60 patients with a diagnosis of
      relapsing-remitting MS and 60 age- and sex-matched controls without neurological
      impairments. A questionnaire recommended by the European Academy of
      Craniomandibular Disorders for the assessment of TMD symptoms was administered.
      For those who answered affirmatively to at least one of the questions, the
      RDC/TMD Axis I instrument was used for a possible classification of TMD subtypes.
      The Expanded Disability Status Scale (EDSS) was the measure of the degree of MS
      related disability. Statistical Analysis Used: Fisher's exact test was used to
      analyze the data. ANOVA was used to detect significant differences between means
      and to assess whether the factors influenced any of the dependent variables by
      comparing means from the different groups. Results: The prevalence of TMD
      symptoms in patients with MS was 61.7% versus 18.3% in the control group (CG). A
      diagnosis of TMD was established for 36.7% in the MS group and 3.3% in the CG (P
      = 0.0001). There were statistically significant differences between degrees of MS
      related disability and the prevalence of TMD (P = 0.0288). Conclusions: The
      prevalence of both TMD and TMD symptoms was significantly greater in the MS
      group. EDSS scores and TMD prevalence rates were inversely related.

PMID- 29657541
TI  - Gingival melanin depigmentation by 810 nm diode laser.
AB  - The color of gingiva is determined by number and size of blood vessels, thickness
      of epithelium, keratinization degree, and melanin pigments present in epithelium.
      Melanocytes, located in basal and suprabasal layers of epithelium, are the cells
      that produce melanin pigments which play a main role for pigmentation of gingiva.
      In this case series, the use of 810 nm diode laser for depigmentation of gingiva
      is presented. Two female patients applied with a chief complaint of "darkened
      gums" due to heavy smoking. In intraoral examination, diffuse melanin
      pigmentation was observed in both the maxilla and mandible. Under the local
      anesthesia, 810 nm diode laser was applied for depigmentation at 1.3 W power in
      continuous mode. Patients were recalled at weeks 1, 4, and 12 to evaluate the
      healing and recurrence rate. Both the patients had no postoperative pain or
      edema, and complete healing was observed at week 12. This study revealed that
      depigmentation with 810 nm diode laser is successful in terms of esthetics and
      patient comfort.

PMID- 29657542
TI  - Accuracy of computer-guided surgery for dental implant placement in fully
      edentulous patients: A systematic review.
AB  - Assess clinical studies regarding accuracy between virtual planning of computer
      guided surgery and actual outcomes of dental implant placements in total
      edentulous alveolar ridges. A PubMed search was performed to identify only
      clinical studies published between 2011 and 2016, searching the following
      combinations of keywords: "Accuracy AND Computer-Assisted Surgery AND Dental
      Implants." Study designs were identified using the terms: Case Reports, Clinical
      study, Randomized Controlled Trial, Systematic Reviews, Meta-Analysis, humans.
      Level of agreement between the authors in the study selection process was
      substantial (k = 0.767), and the study eligibility was considered excellent (k =
      0.863). Seven articles were included in this review. They describe the use of
      bone and muco-supported guides, demonstrating angular deviations cervically and
      apically ranging from (minimum and maximum means), respectively, 1.85-8.4 (
      degrees ), 0.17-2.17 (mm), and 0.77-2.86 (mm). Angular deviations obtained most
      inaccuracy in maxila. For cervical and apical deviations, accuracy was
      preponderantly lower in maxilla. Despite the similar deviations measurement
      approaches described, clinical relevance of this study may be useful to warn the
      surgeon that safety margins in clinical situations.

PMID- 29657543
TI  - Association of ABO and Rh blood groups with breast cancer.
AB  - Objectives: The aim of this study was to determine the association of "ABO" and
      "Rhesus" blood groups with incidence of breast cancer. Methods: In this study, we
      identified 70 research documents from data based search engines including
      "PubMed", "ISI-Web of Knowledge", "Embase" and "Google Scholar". The research
      papers were selected by using the primary key-terms including "ABO blood type",
      "Rhesus" blood type and "breast cancer". The research documents in which "ABO"
      and "Rhesus" blood types and breast cancer was debated were included. After
      screening, we reviewed 32 papers and finally we selected 25 research papers which
      met the inclusion criteria and remaining documents were excluded. Results: Blood
      group "A" has high incidence of breast cancer (45.88%), blood group "O" has
      (31.69%); "B" (16.16%) and blood group "AB" has (6.27%) incidence of breast
      cancer. Blood group "A" has highest and blood group "AB" has least association
      with breast cancer. Furthermore, "Rhesus +ve" blood group has high incidence of
      breast cancer (88.31%) and "Rhesus -ve" blood group has least association with
      breast cancer (11.68%). Conclusion: Blood group "A" and "Rhesus +ve" have high
      risk of breast cancer, while blood type "AB" and "Rhesus -ve" are at low peril of
      breast cancer. Physicians should carefully monitor the females with blood group
      "A" and "Rh +ve" as these females are more prone to develop breast cancer. To
      reduce breast cancer incidence and its burden, preventive and screening programs
      for breast cancer especially in young women are highly recommended.

PMID- 29657544
TI  - A Remote Sensing-Based Tool for Assessing Rainfall-Driven Hazards.
AB  - RainyDay is a Python-based platform that couples rainfall remote sensing data
      with Stochastic Storm Transposition (SST) for modeling rainfall-driven hazards
      such as floods and landslides. SST effectively lengthens the extreme rainfall
      record through temporal resampling and spatial transposition of observed storms
      from the surrounding region to create many extreme rainfall scenarios. Intensity
      Duration-Frequency (IDF) curves are often used for hazard modeling but require
      long records to describe the distribution of rainfall depth and duration and do
      not provide information regarding rainfall space-time structure, limiting their
      usefulness to small scales. In contrast, RainyDay can be used for many hazard
      applications with 1-2 decades of data, and output rainfall scenarios incorporate
      detailed space-time structure from remote sensing. Thanks to global satellite
      coverage, RainyDay can be used in inaccessible areas and developing countries
      lacking ground measurements, though results are impacted by remote sensing
      errors. RainyDay can be useful for hazard modeling under nonstationary
      conditions.

PMID- 29657545
TI  - Uninsured Migrants: Health Insurance Coverage and Access to Care Among Mexican
      Return Migrants.
AB  - Background: Despite an expansive body of research on health and access to medical
      care among Mexican immigrants in the United States, research on return migrants
      focuses primarily on their labor market mobility and contributions to local
      development. Objective: Motivated by recent scholarship that documents poor
      mental and physical health among Mexican return migrants, this study investigates
      return migrants' health insurance coverage and access to medical care. Methods: I
      use descriptive and multivariate techniques to analyze data from the 2009 and
      2014 rounds of Mexico's National Survey of Demographic Dynamics (ENADID, combined
      n=632,678). Results: Analyses reveal a large and persistent gap between recent
      return migrants and non-migrants, despite rising overall health coverage in
      Mexico. Multivariate analyses suggest that unemployment among recent arrivals
      contributes to their lack of insurance. Relative to non-migrants, recently
      returned migrants rely disproportionately on private clinics, pharmacies, self
      medication, or have no regular source of care. Mediation analysis suggests that
      returnees' high rate of uninsurance contributes to their inadequate access to
      care. Conclusion: This study reveals limited access to medical care among the
      growing population of Mexican return migrants, highlighting the need for targeted
      policies to facilitate successful reintegration and ensure access to vital
      resources such as health care.

PMID- 29657546
TI  - Successful pregnancy outcome using sperm from severely diseased men with
      testicular cancer and collagen disease: Three case reports.
AB  - Objective:  To confirm the feasibility of using fresh or frozen/thawed
      spermatozoa from cancer and collagen diseased patients for intracytoplasmic sperm
      injection (ICSI). Patients:  Two participants were diagnosed with testicular
      carcinoma and one patient was diagnosed with collagen disease. Methods:  Of the
      two carcinoma patients, one patient provided a fresh testicular biopsy sample and
      one patient ejaculated fresh sperm after surgical operation. One collagen
      diseased patient's sperm was frozen, and three samples were used in subsequent
      ICSI treatment cycles. Their female partners underwent controlled ovarian
      hyperstimulation for the retrieval of oocytes. Results:  Two patients with
      testicular cancer and their respective partners achieved successful pregnancies
      from ICSI using fresh sperm after surgery. The patient suffering from collagen
      disease had a successful pregnancy from ICSI using sperm frozen prior to
      chemotherapy treatment. Conclusions:  Patients with testicular carcinoma or
      collagen disease who might desire to father children in the future should be
      offered sperm preservation prior to the initiation of chemotherapy treatment.
      Under currently available treatment, patients with cases of severe disease can
      still become biological fathers. (Reprod Med Biol 2004; 3: 69-75).

PMID- 29657547
TI  - Molecular screening of unculturable bacteria present in men with reproductive
      failure.
AB  - Objective:  To determine the presence of unculturable bacteria using polymerase
      chain reaction (PCR) in infertile men with pyosperrmia. Design:  Perspective
      clinical study. Setting:  The study took place at the Department of Reproductive
      Medicine, Owaisi Hospital and Research Center; In vitro Fertilization Unit,
      Mahavir Hospital and Research Center; Center for Cellular and Molecular Biology;
      and Bharat Biotech Foundation, Hyderabad, India. Patients:  A total of 68
      infertile men and 15 donors, all with no symptoms of genito-urinary tract
      infections and sterile semen cultures were included in the study. Interventions: 
      None. Main outcome measures:  Screening bacteria using routine bacterial cultures
      and PCR based screening with universal eubacterial primers. Results:  The
      statistical analysis of all the semen parameters in asthenazoospermic,
      azoospermic, ceyptazoospermic, severe oligospermic and mild oligospermic patients
      were found to be significant compared with the controls. All the groups were
      found to be significant compared with the controls (P < 0.05) except for volume
      and pus cells in the cryptozoospermia group. The Student's t-test also was
      significant for the seminal parameters before and after treatment of 68 selected
      individuals with pyospermia and sterile cultures. A total of 44.11% (30/68)
      samples were collected from the negative culture of pyospermic infertile men have
      shown the presence of bacteria on amplification using PCR with universal
      eubacterial primers. The DNA was purified and sequenced. The sequences were
      checked for homology using DNASTAR and Ribosomal DataBase Project II. A total of
      90% of the samples have shown the nearest evolutionary relation to Pantoea P102
      (AF394539) and 10% of samples have shown close relation with Burkholderia cepacia
      (AF042161). Conclusion:  The routine bacteriological cultures were unable to
      detect certain bacterial species particularly with members of enterobacteriaceae
      family (Pantoea species). Polymerase chain reaction, when used for screening
      bacteria, can detect the unculturable form of bacteria in infertile men. No
      amplification for bacterial DNA was obtained in control samples (fertile men with
      sterile semen cultures.) (Reprod Med Biol 2004; 3: 77- 84).

PMID- 29657548
TI  - Effects of dibromoacetic acid on murine spermatozoa and testis.
AB  - Background and Aims:   Bromoacetic acids are a by-product of water ozonation and
      dibromoacetic acid (DBAA) in particular, which is a by-product of disinfection,
      inhibits male reproductive functions. In order to understand its effects, the
      spermatozoa and testes of mice were exposed to DBAA. Methods:   Twelve-week-old
      ICR mice were exposed to 10 p.p.m. DBAA. They were examined in regards to effects
      on the weights of body, testis and epididymis, the histological changes of tesits
      and the protein expression in testis. Results:   Neither the bodyweight nor the
      weights of the testis and epididymis of the exposed mice was affected, but
      approximately 13% of spermatozoa obtained from the cauda epididymis were motile
      with a drop-shaped head, and structures resembling residual bodies were found in
      the testis. Moreover, the expression of two testis proteins was changed by
      exposure to DBAA. Conclusions:   It was likely that DBAA inhibited male
      reproductive functions by disturbance of spermatogenesis via change of protein
      expression. (Reprod Med Biol 2004; 3: 85-93).

PMID- 29657550
TI  - Accelerated decline in pregnancy rate after in vitro fertilization and embryo
      transfer in 35-41-year-old women: 15 years' experience in the Okinawa Islands,
      Japan.
AB  - Aim:  To describe 15 years of in vitro fertilization and embryo transfer (IVF-ET)
      treatment at University Hospital, with special reference to a potential
      association between pregnancy rate and patient age. Methods:  A retrospective
      analysis of 2355 IVF-ET cycles carried out in 789 patients was undertaken. The
      main outcome measures were ovarian response, fertilization rate and pregnancy
      rate. Results:  Pregnancy rates in ET cycles carried out in women aged between 23
      and 46 years fell significantly with patient age, with a more rapid decline after
      35 years and particularly between 35 and 41 years. Almost all laboratory findings
      were significantly worse with increased patient age, although fertilization rate
      did not drop with age. The spontaneous abortion rate increased drastically with
      age and the vast majority of abortions resulted from chromosomal abnormality.
      Conclusion:  It is essential to provide infertile women with practical and
      reliable information on the age-associated pregnancy rate for appropriate
      counseling and to encourage them to seek IVF-ET treatment at an earlier age.
      (Reprod Med Biol 2006; 5: 51-57).

PMID- 29657549
TI  - Regulation of testicular function by cell-to-cell interaction.
AB  - Cell-to-cell interactions in the testis play important roles in regulating
      testicular function. Investigating the mechanism of such interactions is
      essential to elucidate the cause of spermatogenic dysfunction and to create a new
      treatment. (Reprod Med Biol 2006; 5: 9-17).

PMID- 29657551
TI  - Recombinant-follicle stimulating hormone is more effective than urinary human
      menopausal gonadotropin in ovarian hyperstimulation for assisted reproductive
      technology treatment.
AB  - Aim:  The aim of the present study was to establish a standard protocol for
      ovarian stimulation with gonadotropin-releasing hormone analog (GnRH-a) long
      protocol using recombinant-follicle stimulating hormone (rec-FSH) preparations
      for assisted reproductive technology (ART) treatment. Methods:  In 86 patients
      who underwent ovarian stimulation with GnRH-a long protocol for ART treatment, 53
      were stimulated by rec-FSH preparations (rec-FSH group) and the others were
      stimulated by urinary-hMG (u-hMG group) preparations. The subjects were randomly
      assigned to either of these preparations. Hormonal profiles, total doses of
      gonadotropins, duration of stimulation and ART results were compared in both
      groups. Results:  The duration of stimulation was similar in both groups (9.2 +/-
      0.3 days and 9.2 +/- 0.2 days, respectively). The total doses of gonadotropin in
      the rec-FSH group (1505.3 +/- 29.2 IU) was significantly lower than those in the
      u-hMG group (2130.3 +/- 54.6 IU, P < 0.0001). The FSH and LH values on the day of
      human chorionic gonadotropin (hCG) administration in the rec-FSH group were
      significantly lower than those in the u-hMG group. Pregnancy rates were 31.3% in
      the rec-FSH group and 33.3% in the u-hMG group, respectively. Conclusions:  The
      present study showed that rec-FSH preparations were more potent than conventional
      u-hMG preparations and the protocol of the present study with rec-FSH was a new
      ovarian stimulation protocol with GnRH-a long protocol. (Reprod Med Biol 2007; 6:
      27-32).

PMID- 29657552
TI  - High incidence of tubal dysfunction is determined by laparoscopy in cases with
      positive Chlamydia trachomatis antibody despite negative finding in prior
      hysterosalpingography.
AB  - Aim:  Hysterosalpingography (HSG) is one of the most commonly used methods in
      order to evaluate the condition of fallopian tubes in infertility clinics. In the
      present paper, we retrospectively compared the findings of HSG and laparoscopy to
      elucidate the relationship between tubal dysfunction and background factors, such
      as Chlamydia trachomatis infection, endometriosis and previous surgery. Methods: 
      We retrospectively reviewed clinical records of 314 patients who were examined by
      both HSG and laparoscopy between 1996 and 2001 in the Department of Obstetrics
      and Gynecology, University of Tokyo. Results:  When HSG findings were evaluated
      in reference to those of laparoscopy, sensitivity and specificity for tubal
      patency were 0.63 and 0.79, respectively, whereas those for peri-tubal adhesion
      were 0.65 and 0.61, respectively. We compared the percentage of existence of
      background factors between the patients who were diagnosed as normal by both HSG
      and laparoscopy (Group L[+]) and those whose fallopian tubes were observed as
      patent by HSG, but were not patent by chromopertubation under laparoscopy (Group
      L[-]). The percentage of patients with positive chlamydial antibodies in Group L(
      ) (42.9%, 15/35) was significantly higher than that of patients with positive
      chlamydial antibodies in Group L(+) (22.8%, 44/193, P < 0.05). Conclusions: 
      These finding suggested that even if HSG showed normally patent tubes in a
      patient with positive Chlamydia trachomatis antibodies, the possibility of tubal
      occulusion still remains high and further examination by laparoscopy is
      recommended. (Reprod Med Biol 2007; 6: 39-43).

PMID- 29657553
TI  - A study of the effect of an extremely low oxygen concentration on the development
      of human embryos in assisted reproductive technology.
AB  - Purpose: To determine whether embryos cultured with a low oxygen level (2%)
      brought about beneficial effects on the outcome of ART. Methods: This is a
      sequential case-control embryo-culture study. Embryos were cultured either with a
      gas mixture containing 2% O2, 5% CO2, and 93% N2 (low-oxygen group) or 5% O2, 5%
      CO2, and 90% N2 (conventional group). From January 2008 to September 2008, 873
      fertilized oocytes were obtained from 250 patients in the low-oxygen group and
      from October 2008 to March 2009, 730 fertilized oocytes were obtained from 213
      patients in the conventional group. The outcomes of ART were compared between two
      groups. Results: The cleavage rate in the low-oxygen group (94.4%) was similar to
      that (94.7%) in the conventional group. The mean number of blastomeres on Day 3
      in the low-oxygen group (mean +/- SE) was 6.5 +/- 1.9, and this was significantly
      lower than in the conventional group (6.8 +/- 1.9, p < 0.05). Moreover, the low
      oxygen group produced worse quality embryos, on the basis of the significantly
      higher embryo grade 2.1 +/- 0.6 versus 1.9 +/- 0.6, p < 0.001, in 5% oxygen. The
      pregnancy and miscarriage rates in the low-oxygen group were 22.3 and 20.8%,
      respectively, which were statistically similar to the outcomes in the
      conventional group. Conclusions: Overall, culture of embryos at the low oxygen
      level did not significantly improve ART results compared with embryos grown in 5%
      oxygen. The study suggests that a low oxygen level worsens embryo morphology but
      does not impair embryo viability.

PMID- 29657554
TI  - Electrochemically-induced reduction of nitrate in aqueous solution.
AB  - In this study, we evaluated the removal of nitrate from synthetic groundwater by
      a cathode followed by an anode electrode sequence in the electrochemical flow
      through reactor. We also tested the feasibility of the used electrode sequence to
      minimize the production of ammonia during the nitrate reduction. The performance
      of monometallic Fe, Cu, Ni and carbon foam cathodes was tested under different
      current intensities, flow rates/regimes and the presence of Pd and Ag catalyst
      coating. With the use of monometallic Fe and an increase in current intensity
      from 60 mA to 120 mA, the nitrate removal rate increased from 7.6% to 25.0%, but
      values above 120 mA caused a decrease in removal due to excessive gas formation
      at the electrodes. Among tested materials, monometallic Fe foam cathode showed
      the highest nitrates removal rate and increased significantly in the presence of
      Pd catalyst: from 25.0% to 39.8%. Further, the circulation under 3 mL min-1
      elevated the nitrate removal by 33% and the final nitrate concentration fell
      below the maximum contaminant level of 10 mg L-1 nitrate-nitrogen (NO3-N). During
      the treatment, the yield of ammonia production after the cathode was 92+/-4%
      while after the anode (Ti/IrO2/Ta2O5), the amount of ammonia significantly
      declined to 50%. The results proved that flow-through, undivided electrochemical
      systems can be used to remove nitrate from groundwater with the possibility of
      simultaneously controlling the generation of ammonia.

PMID- 29657555
TI  - The role of candidate evaluations in the 2014 European Parliament elections:
      Towards the personalization of voting behaviour?
AB  - We study the personalization of voting behaviour in European Parliament
      elections. We argue that information from the media is crucial for providing
      linkages between candidates and voters. Moreover, we contend that candidates can
      serve as information short-cuts given the complexity of European Union politics.
      We use a four-wave Dutch panel survey and a media study that enable us to link
      evaluations of lead candidates, party preferences, and vote choice to exposure to
      news about these candidates. We show, firstly, that exposure to candidate news is
      a strong explanatory factor for candidate recognition. Secondly, we find that
      candidate evaluations positively affect party choice, albeit mainly for those
      voters who tend to be politically aware. Our research has implications for
      debates about the European Union's accountability deficit.

PMID- 29657556
TI  - Care in Nursing Facilities after Palliative Consult.
AB  - Despite hospital palliative care consultations during which goals of care are
      discussed in the context of poor prognoses, older adults are admitted to nursing
      homes for post-acute care where the focus is on rehabilitation. The purpose of
      this qualitative descriptive study was to describe factors that influence
      discontinuity between a palliative care consult and nursing home care and explore
      the potential consequences of this discontinuity. Twelve adults (mean age of 80
      years) were enrolled from one community hospital and nursing home in the mid
      Atlantic United States. Semi-structured interviews and medical record reviews
      were used to elicit information about clinical course, care processes, and
      patient/family preferences at hospital discharge and up to four times after
      nursing home admission. Data were analyzed using inductive content analysis
      techniques. Analysis revealed two themes: Inadequate Communication characterized
      by the lack of information about the palliative care consult after hospital
      discharge and Prognosis Incongruence evidenced by data demonstrating a
      discrepancy between hospital prognosis and nursing home care. Ongoing
      communication between settings to re-address goals of care, prognosis, and
      symptoms-the central tenets of palliative care-is lacking. Efforts to improve
      access to comprehensive palliative care delivery after hospitalization and during
      nursing home transitions are greatly needed.

PMID- 29657557
TI  - Learning Subnetwork Biomarkers via Hypergraph for Classification of Autism
      Disease.

PMID- 29657558
TI  - Portraits of Well-Being: Photography as a Mental Health Support for Women With
      HIV.
AB  - Many women living with HIV/AIDS (WL-HIV/AIDS) experience significant mental
      distress. Although creative arts strategies are well positioned to help support
      women by inspiring creativity and meaning-making, few arts programs have been
      implemented and evaluated with this population. We conducted a photography
      project with thirty WL-HIV/AIDS from three United States cities. Participants
      took pictures to capture their life with HIV/AIDS and described their photos and
      stories in group and individual sessions. Using thematic analysis, we identified
      that the project supported women's mental health in four ways by facilitating
      empowerment and helping women to express themselves, address their mental health
      with new tools like photography, and process past traumas. Photography projects
      may help WL-HIV/AIDS understand and manage their mental health.

PMID- 29657559
TI  - Activation peptide of the coagulation factor XIII (AP-F13A1) as a new biomarker
      for the screening of colorectal cancer.
AB  - Background: Colorectal cancer (CRC) remains a major cause of cancer fatalities in
      developed countries. The risk of death is correlated to the stage of CRC during
      the primary diagnosis. Early diagnosis is closely associated with enhanced
      survival rate. We therefore investigated the AP-F13A1 as a potential protein
      marker of CRC. Methods: The protein expression of FXIII in 40 serum samples was
      evaluated by enzyme-linked immunosorbent assays. Additionally, targeted proteomic
      assays (LC-PRM) were used to evaluate the expression of the activation peptide of
      F13A1 (AP-F13A1) in a further 113 serum samples. Results were analyzed by the
      Wilcoxon test and receiver operating characteristic curves generated to assess
      statistical differences and diagnostic factors between CRC patients and controls.
      Results: AP-F13A1 was quantified in human serum samples using calibration curves
      with excellent linearity. AP-F13A1 was reduced in CRC patients using PRM assays
      from two distinct biobanks. The AUC for AP-F13A1 were 0.95 and 0.93.
      Sensitivity/specificity values for the two sets of patients were 75%/95% and
      71%/95% respectively. Conclusion: We have presented the proof of principle that
      in vivo release of AP-F13A1 can be measured by PRM-based strategies in CRC serum
      samples. AP-F13A1 may be an effective serological biomarker as part of a
      screening program of CRC detection.

PMID- 29657560
TI  - Analyzing user interactions with biomedical ontologies: A visual perspective.
AB  - Biomedical ontologies are large: Several ontologies in the BioPortal repository
      contain thousands or even hundreds of thousands of entities. The development and
      maintenance of such large ontologies is difficult. To support ontology authors
      and repository developers in their work, it is crucial to improve our
      understanding of how these ontologies are explored, queried, reused, and used in
      downstream applications by biomedical researchers. We present an exploratory
      empirical analysis of user activities in the BioPortal ontology repository by
      analyzing BioPortal interaction logs across different access modes over several
      years. We investigate how users of BioPortal query and search for ontologies and
      their classes, how they explore the ontologies, and how they reuse classes from
      different ontologies. Additionally, through three real-world scenarios, we not
      only analyze the usage of ontologies for annotation tasks but also compare it to
      the browsing and querying behaviors of BioPortal users. For our investigation, we
      use several different visualization techniques. To inspect large amounts of
      interaction, reuse, and real-world usage data at a glance, we make use of and
      extend PolygOnto, a visualization method that has been successfully used to
      analyze reuse of ontologies in previous work. Our results show that exploration,
      query, reuse, and actual usage behaviors rarely align, suggesting that different
      users tend to explore, query and use different parts of an ontology. Finally, we
      highlight and discuss differences and commonalities among users of BioPortal.

PMID- 29657562
TI  - Mental Health Disorder Therapeutic Modalities Modified for the GMS.
AB  - Background: Mental health disorders can affect physical and psychological
      behaviors. The people of the Greater Mekong Subregion (GMS) have a high risk of
      mental health disorders, such as depression, stress, and substance abuse be-cause
      the people in this region are trafficked for forced sex work and various forms of
      forced labor. In these situations, vic-tims often endure violence and abuse from
      trafficking recruiters, employers, and other individuals. The purposes of this
      study were to identify the elements characterizing mental health disorders,
      especially in terms of depression, stress, and sub-stance abuse, and to identify
      the treatment modalities for mental health disorders in the GMS. Methods: The
      researcher undertook a comparative analysis of the literature, reviews of
      epidemiological studies and mental disorder therapies, and overviews of previous
      research studies, were used to generate a synthesis of the existing knowledge of
      the mental disorder therapeutic modalities. Regarding the search methods, the
      data from the electronic databases PubMed, PsycINFO, Dynamed and ScienceDirect
      were supplemented with a manual reference search covering relevant studies from
      2005 to 2016. Results: Thirty-one papers were included in the review of elements
      characterizing mental health disorders, especially in terms of depression,
      stress, and substance abuse, and to identify the treatment modalities for mental
      health disorders in the GMS. Nine papers defined characterizing mental health
      disorders, in terms of depression, stress, and substance abuse. Twenty-two papers
      showed the treatment modalities for mental health disorders that the treatment
      was effective, these in-cluded pharmacological treatments and psychological
      treatments, such as mindfulness-based cognitive therapy, biofeedback, and music
      therapy. Useful guidance can be provided for the prevention and treatment of
      mental health disorders, and for the care of people in the Greater Mekong
      Subregion. Conclusion: The finding of this review confirms the therapeutic
      modalities can provide useful guidance for the prevention and treatment of mental
      health disorders and the care of the people in the Greater Mekong Sub-region. In
      addition, the effective interventions should be tested regarding their
      suitability for the socio-cultural context in the Greater Mekong Subregion.

PMID- 29657561
TI  - Habitual Sleep and human plasma metabolomics.
AB  - Introduction: Sleep plays an important role in cardiometabolic health. The sleep
      wake cycle is partially driven by the endogenous circadian clock, which governs a
      range of metabolic pathways. The association between sleep and cardiometabolic
      health may be mediated by alterations of the human metabolome. Objectives: To
      better understand the biological mechanism underlying the association between
      sleep and health, we examined human plasma metabolites in relation to sleep
      duration and sleep timing. Methods: Using an untargeted approach, 329 fasting
      plasma metabolites were measured in 277 Chinese participants. We measured sleep
      timing (midpoint between bedtime and wake up time) using repeated time-use
      surveys (4 weeks during one year) and previous night sleep duration from
      questionnaires completed before sample donation. Results: We found 64 metabolites
      that were associated with sleep timing with a false discovery rate of 0.2 or
      lower, after adjusting for potential confounders. Notably, we found that later
      sleep timing was associated with higher levels of multiple metabolites in amino
      acid metabolism, including branched chain amino acids and their gamma-glutamyl
      dipeptides. We also found widespread associations between sleep timing and
      numerous metabolites in lipid metabolism, including bile acids, carnitines and
      fatty acids. In contrast, previous night sleep duration was not associated with
      plasma metabolites in our study. Conclusion: Sleep timing was associated with a
      large number of metabolites across a variety of biochemical pathways. Some
      metabolite associations are consistent with a relationship between late
      chronotype and adverse effects on cardiometabolic health.

PMID- 29657564
TI  - Optimization of moderators and beam extraction at the ESS.
AB  - A global approach coupling the moderator to the beam extraction system has been
      applied for the design optimization of the thermal and cold moderators of the
      European Spallation Source (ESS), which will be the brightest neutron source in
      the world for condensed-matter studies. The design is based on the recently
      developed high-brightness low-dimensional moderator concepts. Para-hydrogen is
      used for the cold neutron source, while thermal neutrons are provided by
      moderation in water. The overall moderation configuration was chosen in order to
      satisfy a range of requirements on bispectral extraction, beamport configuration
      and instrument performance. All instruments are served by a single moderator
      assembly above the target, arranged in a 'butterfly' geometry with a height of 3
      cm. This was determined to be the optimal height for trade-off between high
      brightness and efficient guide illumination, by analysis of the performance of 23
      instruments, based on the reference suite of the ESS Technical Design Report. The
      concept of 'brilliance transfer' is introduced to quantify the performance of the
      neutron optical system from the source to the sample. The target monolith
      incorporates a grid of 42 neutron beamports with an average separation of 6
      degrees , allowing a free choice between cold and thermal neutron sources at all
      instrument positions. With the large number of beamports and the space below the
      target available for future moderators, ample opportunities are available for
      future upgrades.

PMID- 29657563
TI  - Influence of Culture in Obsessive-compulsive Disorder and Its Treatment.
AB  - Background: The aspects of cultural identity and its impact on obsessive
      compulsive disorder (OCD) have been un-derstudied. There are different opinions,
      ranging from the idea that culture does not affect the symptoms of this condition
      to the idea that cultures with high religiosity may have more severity of OCD.
      Also, the concept of OCD has considerably var-ied across history and cultures,
      from being considered an issue related to lack of control of blasphemous ideas,
      and a part of anxious issues, to the description of complex neurobiological
      systems in its causation. Objective: The aim of this review was to address OCD as
      a well-characterized disorder with a proposed neurobiological ba-sis which may or
      may not have variations depending on cultural diversity. The question that was
      asked in this review is whether or not there are cultural differences in the
      manifestations of the OCD symptomatology and which factors of cultural diversity
      have a major influence on such manifestations along with the differences among
      some cultures regarding OCD is-sues, where the difference among countries has
      also been highlighted. Methods: A review of the literature was conducted that
      includes the following words: obsessive-compulsive disorder, cul-ture, cultural
      identity and religion in a period of 10 years. Conclusion: Cultural variations do
      not seem to differ from symptomatic clusters of OCD, which may be indicating that
      a se-ries of adaptive behaviors is evolutionarily evolving to be constantly
      altered, perhaps by well-determined pathophysiological mechanisms. Some aspects
      that have been related to some dimensions of OCD symptomatology are religion and
      religiosity, affecting the content of obsessions and the severity of
      manifestations. Properly evaluating the education background, access to health
      services, food, and the genetic structure of populations, using investigational
      instruments sensitive to these cultural elements, will increase our understanding
      of the importance of culture on OCD and its treatment.

PMID- 29657565
TI  - Implementation of cross correlation for energy discrimination on the time-of
      flight spectrometer CORELLI.
AB  - The CORELLI instrument at Oak Ridge National Laboratory is a statistical chopper
      spectrometer designed and optimized to probe complex disorder in crystalline
      materials through diffuse scattering experiments. On CORELLI, the high efficiency
      of white-beam Laue diffraction combined with elastic discrimination have enabled
      an unprecedented data collection rate to obtain both the total and the elastic
      only scattering over a large volume of reciprocal space from a single
      measurement. To achieve this, CORELLI is equipped with a statistical chopper to
      modulate the incoming neutron beam quasi-randomly, and then the cross-correlation
      method is applied to reconstruct the elastic component from the scattering data.
      Details of the implementation of the cross-correlation method on CORELLI are
      given and its performance is discussed.

PMID- 29657566
TI  - The high-intensity option of the SANS diffractometer KWS-2 at JCNS -
      characterization and performance of the new multi-megahertz detection system.
AB  - A new detection system based on an array of 3He tubes and innovative fast
      detection electronics has been installed on the high-intensity small-angle
      neutron scattering (SANS) diffractometer KWS-2 operated by the Julich Centre for
      Neutron Science (JCNS) at the Heinz Meier-Leibnitz Zentrum in Garching, Germany.
      The new detection system is composed of 18 eight-pack modules of 3He tubes that
      work independently of one another (each unit has its own processor and
      electronics). To improve the read-out characteristics and reduce the noise, the
      detection electronics are mounted in a closed case on the rear of the 3He tubes'
      frame. The tubes' efficiency is about 85% (for lambda = 5 A) and the resolution
      slightly better than 8 mm. The new detection system is characterized by a dead
      time constant of 3.3 us per tube and an overall count rate as high as 6 MHz at
      10% dead-time loss. Compared with the old detector this is an improvement by a
      factor of 60. The much higher count rate will shorten the measurement times and
      thus increase the number of experiments possible in a given time period by the
      optimal use of the high flux of up to 2 * 108 n cm-2 s-1 at the sample position.
      Combined with the event-mode operation capability, this will enable new
      scientific opportunities in the field of structural investigations of small soft
      matter and biological systems. The implementation of the detector in the high
      intensity concept on KWS-2, its characterization and its performance based on
      test experiments are reported in this paper.

PMID- 29657568
TI  - The thermal expansion of gold: point defect concentrations and pre-melting in a
      face-centred cubic metal.
AB  - On the basis of ab initio computer simulations, pre-melting phenomena have been
      suggested to occur in the elastic properties of hexagonal close-packed iron under
      the conditions of the Earth's inner core just before melting. The extent to which
      these pre-melting effects might also occur in the physical properties of face
      centred cubic metals has been investigated here under more experimentally
      accessible conditions for gold, allowing for comparison with future computer
      simulations of this material. The thermal expansion of gold has been determined
      by X-ray powder diffraction from 40 K up to the melting point (1337 K). For the
      entire temperature range investigated, the unit-cell volume can be represented in
      the following way: a second-order Gruneisen approximation to the zero-pressure
      volumetric equation of state, with the internal energy calculated via a Debye
      model, is used to represent the thermal expansion of the 'perfect crystal'. Gold
      shows a nonlinear increase in thermal expansion that departs from this Gruneisen
      Debye model prior to melting, which is probably a result of the generation of
      point defects over a large range of temperatures, beginning at T/Tm > 0.75 (a
      similar homologous T to where softening has been observed in the elastic moduli
      of Au). Therefore, the thermodynamic theory of point defects was used to include
      the additional volume of the vacancies at high temperatures ('real crystal'),
      resulting in the following fitted parameters: Q = (V0K0)/gamma = 4.04 (1) * 10-18
      J, V0 = 67.1671 (3) A3, b = (K0' - 1)/2 = 3.84 (9), thetaD = 182 (2) K,
      (vf/Omega)exp(sf/kB) = 1.8 (23) and hf = 0.9 (2) eV, where V0 is the unit-cell
      volume at 0 K, K0 and K0' are the isothermal incompressibility and its first
      derivative with respect to pressure (evaluated at zero pressure), gamma is a
      Gruneisen parameter, thetaD is the Debye temperature, vf, hf and sf are the
      vacancy formation volume, enthalpy and entropy, respectively, Omega is the
      average volume per atom, and kB is Boltzmann's constant.

PMID- 29657567
TI  - A Monte Carlo approach for scattering correction towards quantitative neutron
      imaging of polycrystals.
AB  - The development of neutron imaging from a qualitative inspection tool towards a
      quantitative technique in materials science has increased the requirements for
      accuracy significantly. Quantifying the thickness or the density of
      polycrystalline samples with high accuracy using neutron imaging has two main
      problems: (i) the scattering from the sample creates artefacts on the image and
      (ii) there is a lack of specific reference attenuation coefficients. This work
      presents experimental and simulation results to explain and approach these
      problems. Firstly, a series of neutron radiography and tomography experiments of
      iron, copper and vanadium are performed and serve as a reference. These materials
      were selected because they attenuate neutrons mainly through coherent (Fe and Cu)
      and incoherent (V) scattering. Secondly, an ad hoc Monte Carlo model was
      developed, based on beamline, sample and detector parameters, in order to
      simulate experiments, understand the physics involved and interpret the
      experimental data. The model, developed in the McStas framework, uses a priori
      information about the sample geometry and crystalline structure, as well as
      beamline settings, such as spectrum, geometry and detector type. The validity of
      the simulations is then verified with experimental results for the two problems
      that motivated this work: (i) the scattering distribution in transmission imaging
      and (ii) the calculated attenuation coefficients.

PMID- 29657569
TI  - RABDAM: quantifying specific radiation damage in individual protein crystal
      structures.
AB  - Radiation damage remains one of the major limitations to accurate structure
      determination in protein crystallography (PX). Despite the use of cryo-cooling
      techniques, it is highly probable that a number of the structures deposited in
      the Protein Data Bank (PDB) have suffered substantial radiation damage as a
      result of the high flux densities of third generation synchrotron X-ray sources.
      Whereas the effects of global damage upon diffraction pattern reflection
      intensities are readily detectable, traditionally the (earlier onset) site
      specific structural changes induced by radiation damage have proven difficult to
      identify within individual PX structures. More recently, however, development of
      the BDamage metric has helped to address this problem. BDamage is a quantitative,
      per-atom metric identifies potential sites of specific damage by comparing the
      atomic B-factor values of atoms that occupy a similar local packing density
      environment in the structure. Building upon this past work, this article presents
      a program, RABDAM, to calculate the BDamage metric for all selected atoms within
      any standard-format PDB or mmCIF file. RABDAM provides several useful outputs to
      assess the extent of damage suffered by an input PX structure. This free and open
      source software will allow assessment and improvement of the quality of PX
      structures both previously and newly deposited in the PDB.

PMID- 29657570
TI  - Fluorescent Nanomaterials for the Development of Latent Fingerprints in Forensic
      Sciences.
AB  - This review presents an overview on the application of latent fingerprint
      development techniques in forensic sciences. At present, traditional developing
      methods such as powder dusting, cyanoacrylate fuming, chemical method, and small
      particle reagent method, have all been gradually compromised given their emerging
      drawbacks such as low contrast, sensitivity, and selectivity, as well as high
      toxicity. Recently, much attention has been paid to the use of fluorescent
      nanomaterials including quantum dots (QDs) and rare earth upconversion
      fluorescent nanomaterials (UCNMs) due to their unique optical and chemical
      properties. Thus, this review lays emphasis on latent fingerprint development
      based on QDs and UCNMs. Compared to latent fingerprint development by traditional
      methods, the new methods using fluorescent nanomaterials can achieve high
      contrast, sensitivity, and selectivity while showing reduced toxicity. Overall,
      this review provides a systematic overview on such methods.

PMID- 29657572
TI  - Editorial.

PMID- 29657573
TI  - New Adipokines Linked to Obesity and Obesity-Related Diseases.
AB  - Adipose tissue plays essential metabolic roles, not only serving as massive
      energy reservoir but also producing and releasing hormones and other biologically
      active molecules that regulate several metabolic activities. Adipocytes secrete a
      variety of factors, referred to as adipokines. Current research has identified
      over 50 adipocyte-secreted factors, and more are yet to be discovered. In
      obesity, increased production of pro-inflammatory adipokines and diminished
      synthesis of anti-inflammatory factors impacts on multiple functions such as
      appetite and energy balance, immunity, insulin sensitivity, angiogenesis, blood
      pressure and lipid metabolism. All are linked with higher risk for cardiovascular
      disease. Various adipocyte-released compounds profoundly affect insulin
      sensitivity and might potentially link obesity-related diseases, including
      atherosclerotic cardiovascular disease, type 2 diabetes mellitus, hypertension,
      dyslipidaemia and insulin resistance. This review aims to present some of the
      recent topics of selected adipokine research that may be of particular
      importance.

PMID- 29657571
TI  - Ice-Templated Protein Nanoridges Induce Bone Tissue Formation.
AB  - Little is known about the role of biocompatible protein nanoridges in directing
      stem cell fate and tissue regeneration due to the difficulty in forming protein
      nanoridges. Here an ice-templating approach is proposed to produce semi-parallel
      pure silk protein nanoridges. The key to this approach is that water droplets
      formed in the protein films are frozen into ice crystals (removed later by
      sublimation), pushing the surrounding protein molecules to be assembled into
      nanoridges. Unlike the flat protein films, the unique protein nanoridges can
      induce the differentiation of human mesenchymal stem cells (MSCs) into
      osteoblasts without any additional inducers, as well as the formation of bone
      tissue in a subcutaneous rat model even when not seeded with MSCs. Moreover, the
      nanoridged films induce less inflammatory infiltration than the flat films in
      vivo. This work indicates that decorating biomaterials surfaces with protein
      nanoridges can enhance bone tissue formation in bone repair.

PMID- 29657574
TI  - The Impairment of Methyl Metabolism From luxS Mutation of Streptococcus mutans.
AB  - The luxS gene is present in a wide range of bacteria and is involved in many
      cellular processes. LuxS mutation can cause autoinducer(AI)-2 deficiency and
      methyl metabolism disorder. The objective of this study was to demonstrate that,
      in addition to AI-2-mediated quorum sensing (QS), methyl metabolism plays an
      important role in LuxS regulation in Streptococcus mutans. The sahH gene from
      Pseudomonas aeruginosa was amplified and introduced into the S. mutans luxS-null
      strain to complement the methyl metabolism disruption in a defective QS
      phenotype. The intracellular activated methyl cycle (AMC) metabolites [S
      adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), homocysteine (HCY), and
      methionine] were quantified in wild-type S. mutans and its three derivatives to
      determine the metabolic effects of disrupting the AMC. Biofilm mass and
      structure, acid tolerance, acid production, exopolysaccharide synthesis of
      multispecies biofilms and the transcriptional level of related genes were
      determined. The results indicated that SAH and SAM were relatively higher in S.
      mutans luxS-null strain and S. mutans luxS null strain with plasmid pIB169 when
      cultured overnight, and HCY was significantly higher in S. mutans UA159.
      Consistent with the transcriptional profile, luxS deletion-mediated impairment of
      biofilm formation and acid tolerance was restored to wild-type levels using
      transgenic SahH. These results also suggest that methionine methyl metabolism
      contributes to LuxS regulation in S. mutans to a significant degree.

PMID- 29657575
TI  - What rates of glaucoma progression are clinically significant?
AB  - Clinically important rates of glaucoma progression (worsening) are ones that put
      a patient at risk of future functional impairment or reduction of vision-related
      quality of life. Rates of progression can be evaluated through measuring
      structural or functional changes of the optic nerve. Most treated eyes do not
      progress at rates that will lead to future visual impairment, but there are a
      significant proportion (3-17%) of eyes, that are at risk of impairment even under
      clinical care. While very fast rates of progression (e.g. MD progression of -1.5
      dB/year) are generally problematic, much slower rates also may be deleterious for
      young patients, particularly those diagnosed with late disease. As a result, it
      is important to consider life expectancy, disease severity and vision-related
      quality of life based treatment targets to estimate future prognosis when
      evaluating whether a rate of glaucoma progression can be clinically relevant.

PMID- 29657576
TI  - High-speed optical coherence tomography by circular interferometric ranging.
AB  - Existing three-dimensional optical imaging methods excel in controlled
      environments but are difficult to deploy over large, irregular and dynamic
      fields. This has limited imaging in areas such as material inspection and
      medicine. To better address these applications, we developed methods in optical
      coherence tomography (OCT) to efficiently interrogate sparse scattering fields,
      i.e., those in which most locations (voxels) do not generate meaningful signal.
      Frequency comb sources are used to superimpose reflected signals from equispaced
      locations through optical subsampling. This results in circular ranging, and
      reduces the number of measurements required to interrogate large volumetric
      fields. As a result, signal acquisition barriers that have limited speed and
      field in OCT are avoided. With a new ultrafast, time-stretched frequency comb
      laser design operating with 7.6 MHz to 18.9 MHz repetition rates, we achieved
      imaging of multi-cm3 fields at up to 7.5 volumes per second.

PMID- 29657577
TI  - The Influence of Affirming Kindness and Community on Broadening Participation in
      STEM Career Pathways.
AB  - The United States' inability to achieve equitable workforce development in
      science, technology, engineering, and mathematics (STEM) career pathways is well
      recognized and has been attributed to the poor retention of a diverse stream of
      students in academia. Social science theory and research provide evidence that
      social contextual variables-specifically kindness cues affirming social inclusion
      influence chronic underrepresentation of some groups within STEM career pathways.
      Review of the literature suggests that the current STEM academic context does not
      consistently provide cues that affirm social inclusion to all members of the
      academic population, and that policies that address this disparity are essential
      to broadening STEM workforce development in the United States.

PMID- 29657578
TI  - Notes from the field: a case of hepatic failure and reflections on current status
      of healthcare of Syrian refugees in Lebanon.
AB  - Recent trends and research suggest health conditions of the Syrian refugees in
      Lebanon are deteriorating. The following case study highlights some of the
      problems that refugees encounter seeking health care services in Lebanon. A
      coordinated response from Non-governmental organization (NGO) with intense focus
      on non-communicable disease (NCD) is needed to avert further worsening of health
      conditions on the ground.

PMID- 29657579
TI  - High-yield production of 1,3-propanediol from glycerol by metabolically
      engineered Klebsiella pneumoniae.
AB  - Background: Glycerol is a major byproduct of the biodiesel industry and can be
      converted to 1,3-propanediol (1,3-PDO) by microorganisms through a two-step
      enzymatic reaction. The production of 1,3-PDO from glycerol using microorganisms
      is accompanied by formation of unwanted byproducts, including lactate and 2,3
      butanediol, resulting in a low-conversion yield. Results: Klebsiella pneumoniae
      was metabolically engineered to produce high-molar yield of 1,3-PDO from
      glycerol. First, the pathway genes for byproduct formation were deleted in K.
      pneumoniae. Then, glycerol assimilation pathways were eliminated and mannitol was
      co-fed to the medium. Finally, transcriptional regulation of the dha operon were
      genetically modified for enhancing 1,3-propanediol production. The batch
      fermentation of the engineered strain with co-feeding of a small amount of
      mannitol yielded 0.76 mol 1,3-PDO from 1 mol glycerol. Conclusions: Klebsiella
      pneumoniae is useful microorganism for producing 1,3-PDO from glycerol.
      Implemented engineering in this study successfully improved 1,3-PDO production
      yield, which is significantly higher than those reported in previous studies.

PMID- 29657580
TI  - Visualizing cellulase adsorption and quantitatively determining cellulose
      accessibility with an updated fungal cellulose-binding module-based fluorescent
      probe protein.
AB  - Background: Cellulose accessibility to cellulases (CAC) is a direct factor
      determining the enzymatic digestibility of lignocellulosic cellulose. Improving
      CAC by pretreatment is a prerequisite step for the efficient release of
      fermentable sugars from biomass cell wall. However, conventional methods to study
      the porosimetry of solid materials showed some limitations to be used for
      investigating CAC. In this work, an updated novel fusion protein comprising a
      fungal cellulose-binding module (CBM) from Cel7A cellobiohydrolase I (CBH I) of
      Trichoderma reesei QM6 and a di-green fluorescent protein (GFP2) was constructed
      for quantitative determination of CAC. Results: The obtained probe protein had
      similar molecular size (e.g., weight) with that of Cel7A and could give
      detectable signal for quantitative analysis. Several construction strategies were
      compared with regard to the site of His-tag and order of CBM and GFP2 modules in
      the protein sequence, in order to achieve good expression quantity and usability
      of the probe protein. His6-CBM-GFP2 has been identified as the best probe protein
      for investigating the effects of structural features of cellulosic substrates on
      cellulose accessibility. Substrate samples with different contents of xylan,
      lignin, and degree of substitution of cellulose -OH by formyl group were
      obtained, respectively, by mild H2SO4 pre-hydrolysis, NaClO2 selective
      delignification, and treatment of filter paper cellulose with concentrated formic
      acid. The determined CAC was in a wide range of 0.6-20.4 m2/g depending on the
      contents of hemicelluloses, lignin, and formyl group as well as cellulose degree
      of crystallization. Conclusions: The obtained fusion probe protein could be used
      as a versatile tool to quantitatively investigate the impacts of biomass
      structural features on CAC and hydrolyzability of cellulose substrates, as well
      as nonproductive adsorption of cellulase enzymes on lignin.

PMID- 29657582
TI  - In-flight performance of the Ozone Monitoring Instrument.
AB  - The Dutch-Finnish Ozone Monitoring Instrument (OMI) is an imaging spectrograph
      flying on NASA's EOS Aura satellite since July 15, 2004. OMI is primarily used to
      map trace gas concentrations in the Earth's atmosphere, obtaining mid-resolution
      (0.4-0.6 nm) UV-VIS (264-504 nm) spectra at multiple (30-60) simultaneous fields
      of view. Assessed via various approaches that include monitoring of radiances
      from selected ocean, land, ice and cloud areas, as well as measurements of line
      profiles in the Solar spectra, the instrument shows low optical degradation and
      high wavelength stability over the mission lifetime. In the regions relatively
      free from the slowly unraveling 'row anomaly' the OMI irradiances have degraded
      by 3-8%, while radiances have changed by 1-2%. The long-term wavelength
      calibration of the instrument remains stable to 0.005-0.020 nm.

PMID- 29657581
TI  - Implications of direct amplification for measuring antimicrobial resistance using
      point-of-care devices.
AB  - Antimicrobial resistance (AMR) is recognized as a global threat to human health.
      Rapid detection and characterization of AMR is a critical component of most
      antibiotic stewardship programs. Methods based on amplification of nucleic acids
      for detection of AMR are generally faster than culture-based approaches but they
      still require several hours to more than a day due to the need for transporting
      the sample to a centralized laboratory, processing of sample, and sometimes DNA
      purification and concentration. Nucleic acids-based point-of-care (POC) devices
      are capable of rapidly diagnosing antibiotic-resistant infections which may help
      in making timely and correct treatment decisions. However, for most POC
      platforms, sample processing for nucleic acids extraction and purification is
      also generally required prior to amplification. Direct amplification, an emerging
      possibility for a number of polymerases, has the potential to eliminate these
      steps without significantly impacting diagnostic performance. This review
      summarizes direct amplification methods and their implication for rapid
      measurement of AMR. Future research directions that may further strengthen the
      possibility of integrating direct amplification methods with POC devices are also
      summarized.

PMID- 29657583
TI  - 'I'm Black and I'm Proud': A Majority Ecological Context Protects Affective
      Aspects of Black Identity Under Stereotype Threat.
AB  - We provide evidence that stereotype threat, a phenomenon that causes stigmatized
      individuals to experience group-based evaluative concerns (Steele in Am Psychol
      52:613-629, 1997; Whistling Vivaldi and other clues to how stereotypes affect us,
      W.W. Norton, New York, 2010), impacts affective aspects of Black identity as a
      function of majority versus minority ecological contexts. Black/African-American
      students, enrolled in either Africana Studies (Black ecological majority) or
      Psychology (Black ecological minority), completed private and public regard
      subscales from the Multidimensional Inventory of Black Identity (Sellers et al.
      in Pers Soc Psychol Rev 2:18-39, 1998) at baseline (Time 1) and after being
      randomly assigned to a stereotype threat or no-threat/control condition (Time 2).
      In threat, participants were introduced to a 'puzzle' task as diagnostic of
      intellectual abilities, whereas in no-threat the same task was introduced as
      culture fair, such that people from different racial/ethnic groups had performed
      similarly on this task in the past. In Psychology, students under threat
      exhibited a simultaneous decrease and increase in private and public regard,
      respectively, a pattern shown in the literature to be associated with
      discrimination-based distress and lesser well-being in Black ecological minority
      environments. In contrast, Africana Studies students' racial identity under
      threat remained intact. We discuss the protective effects of Africana Studies on
      racial identity and implications for educational reform.

PMID- 29657584
TI  - Dynamic Biomarkers of Response to Antiangiogenic Therapies in Colorectal Cancer:
      A Review.
AB  - Background: Identification of clinical and molecular biomarkers to predict
      dynamic response or monitor in real-time the efficacy of antiangiogenic therapy
      represents a major point in the treatment of patients with advanced colorectal
      cancer. Several stu-dies have been conduced to identify some predictive
      biomarkers to select patients who will benefit from bevacizumab, the most widely
      used antiangiogenic monoclonal anti-body. Conclusion: After a decade since the
      introduction of bevacizumab, no effective predictive biomarkers are available in
      routine clinical practice. In this review, we summarized the potential candidate
      dynamic biomarkers that may play a role in this setting.

PMID- 29657585
TI  - Deterioration in saliva quality in patients with Sjogren's syndrome: impact of
      decrease in salivary epidermal growth factor on the severity of intraoral
      manifestations.
AB  - Background: Sjogren's syndrome (SS) is a chronic inflammatory autoimmune disease
      characterized by lymphocytic infiltration of the exocrine glands, especially the
      salivary and lacrimal glands. As a result of salivary gland dysfunction, most
      patients with SS have xerostomia related to a reduced salivary flow rate. In
      addition to the discomfort due to xerostomia, dry mouth can cause various
      intraoral manifestations such as refractory stomatitis, ulcer, and atrophic
      changes in the oral mucosa and tongue, and the patient's quality of life (QoL) is
      severely impaired. These manifestations are believed to be caused mainly by a
      decrease in the clearance in the oral cavity owing to hyposalivation. However,
      because saliva has several beneficial physiological effects on the intraoral
      environment, qualitative changes in sialochemistry should also be considered a
      cause of the refractory intraoral manifestations in SS. Main text: Salivary
      epidermal growth factor (EGF) is considered an important cytoprotective factor
      against injuries. It contributes to wound healing in the oral cavity and to
      maintenance of mucosal integrity in the oral cavity and gastrointestinal tract.
      We evaluated changes in salivary EGF levels and assessed the association between
      salivary EGF levels and the severity of intraoral manifestations in patients with
      SS. The following novel findings were obtained: (1) salivary EGF levels in SS
      patients were significantly lower than those in non-SS patients; (2) salivary EGF
      levels as well as the salivary flow rate decreased with the progression of SS;
      (3) with prolonged SS disease duration, salivary EGF levels decreased more
      rapidly than the salivary flow rate; and (4) decreases in salivary EGF levels
      significantly correlated with exacerbation of the oral health-related QoL in
      patients with SS. Conclusions: The deterioration in saliva quality as well as
      lower intraoral clearance by hyposalivation could play a role in the pathogenesis
      of refractory intraoral manifestations in patients with SS. Our findings suggest
      a new target for therapeutic intervention for SS.

PMID- 29657587
TI  - Impact of ranolazine on ventricular arrhythmias - A systematic review.
AB  - Ranolazine is a new medication for the treatment of refractory angina. However,
      except its anti-anginal properties, it has been found to act as an anti
      arrhythmic. The aim of our systematic review is to present the existing data
      about the impact of ranolazine in ventricular arrhythmias. We searched MEDLINE
      and Cochrane databases as well clinicaltrials.gov until September 1, 2017 to find
      all studies (clinical trials, observational studies, case reports/series)
      reported data about the impact of ranolazine in ventricular arrhythmias. Our
      search revealed 14 studies (3 clinical trials, 2 observational studies, 8 case
      reports, 1 case series). These data reported a beneficial impact of ranolazine in
      ventricular tachycardia/fibrillation, premature ventricular beats, and ICD
      interventions in different clinical settings. The existing data highlight the
      anti-arrhythmic properties of ranolazine in ventricular arrhythmias.

PMID- 29657588
TI  - Portable out-of-hospital electrocardiography: A review of current technologies.
AB  - Background: Availability of portable and home-based electrocardiography (ECG) is
      an important medical innovation, which has a potential to transform medical care.
      We performed this review to understand the current state of out-of-hospital
      portable ECG technologies with respect to their scope, ease of use, data
      transmission capabilities, and diagnostic accuracy. Methods: We conducted PubMed
      and Internet searches for "handheld" or "wearable" or "patch" electrocardiography
      devices to enlist available technologies. We also searched PubMed with names of
      individual devices to obtain additional citations. We classified available
      devices as a "single limb lead ECG recording devices" and chest-lead "ECG
      recording devices." If a device used more than three electrodes, it was defined
      as a conventional electrocardiography or Holter machine and was excluded from
      this review. Results: We identified a total of 15 devices. Overall, only six of
      these devices (five single lead and one chest lead) featured in published medical
      literature as identified from PubMed search. A total of 13 citations were
      available for the single limb lead ECG recording devices and 6 citations for the
      chest-lead ECG recording devices. Conclusions: Despite the increase in number of
      such devices, published biomedical literature regarding their diagnostic
      accuracy, reproducibility, or utility is scant.

PMID- 29657589
TI  - Prognostic significance of nonsustained ventricular tachycardia in patients
      receiving cardiac resynchronization therapy for primary prevention: Analysis of
      the Japan cardiac device treatment registry database.
AB  - Background: Whether nonsustained ventricular tachycardia (NSVT) is a marker of
      increased risk of sustained ventricular tachyarrhythmias (VTAs) remains to be
      established in patients receiving cardiac resynchronization therapy with a
      defibrillator (CRT-D) for primary prevention. Methods: Among the follow-up data
      of the Japan cardiac device treatment registry (JCDTR) with an implantation date
      between January 2011 and August 2015, information regarding a history of NSVT
      before the CRT-D implantation for primary prevention had been registered in 269
      patients. Outcomes were compared between two groups with and without NSVT: NSVT
      group (n = 179) and No NSVT group (n = 90). Results: There was no significant
      difference with regard to age, gender, and NYHA class between the two groups.
      Left ventricular ejection fraction (LVEF) was 25.6% in the NSVT group and 28.0%
      in the No NSVT group (P = .046). The rate of appropriate therapy at 24 months was
      26.0% and 18.4% in the NSVT and No NSVT groups (P = .22), respectively. Survival
      free from heart failure death was reduced in the NSVT group, as compared with the
      No NSVT group, with the rate of 90.2% vs 97.2% at 24 months (P = .030). A
      multivariate analysis identified a history of NSVT, anemia, and no use of
      angiotensin-converting enzyme inhibitor (ACEI) or angiotensin-receptor blocker
      (ARB) as predictors of heart failure death. Conclusions: NSVT appears to be a
      surrogate marker of severe heart failure rather than a substrate for subsequent
      sustained VTAs in patients with CRT-D for primary prevention.

PMID- 29657590
TI  - Comparison of uninterrupted anticoagulation with dabigatran etexilate or warfarin
      in the periprocedural period for atrial fibrillation catheter ablation: Results
      of the Japanese subgroup of the RE-CIRCUIT trial.
AB  - Background: There are limited data on uninterrupted anticoagulation with direct
      oral anticoagulants during catheter ablation for atrial fibrillation (AF),
      particularly in Japan. We planned a subgroup analysis of the RE-CIRCUIT study,
      comparing the use of uninterrupted dabigatran therapy with warfarin therapy
      during catheter ablation among the Japanese subgroup and with that in the total
      population. Methods: The RE-CIRCUIT study utilized a prospective, randomized,
      open-label, blinded endpoint design, and the primary endpoint was the incidence
      of major bleeding events (MBEs). Patients were randomized to uninterrupted
      dabigatran 150 mg twice daily or warfarin. In this study, we analyzed the results
      in Japanese patients. Results: Of 704 enrolled patients in the study, 112
      Japanese patients were randomized to dabigatran (n = 65) or warfarin (n = 47).
      MBEs were experienced by two patients: one in the dabigatran group (1.6%, cardiac
      tamponade) and one in the warfarin group (2.2%, groin hematoma) (risk difference
      vs warfarin -0.6%; 95% CI -5.8, 4.7). Within the Japanese subgroup, there were no
      thromboembolic events in both groups. Conclusion: While not designed to show
      statistical difference between two treatment groups, our results from the
      Japanese subgroup supported those from the overall population. Furthermore, this
      study provided clinical information regarding MBE, especially cardiac tamponade,
      in Japanese patients.

PMID- 29657591
TI  - The lesion characteristics assessed by LGE-MRI after the cryoballoon ablation and
      conventional radiofrequency ablation.
AB  - Background: Rhythm outcomes after the pulmonary vein isolation (PVI) using the
      cryoballoon (CB) are reported to be excellent. However, the lesions after CB
      ablation have not been well discussed. We sought to characterize and compare the
      lesion formation after CB ablation with that after radiofrequency (RF) ablation.
      Methods: A total of 42 consecutive patients who underwent PVI were enrolled (29
      in the CB group and 13 in the RF group). The PVI lesions were assessed by late
      gadolinium enhancement magnetic resonance imaging 1-3 months after the PVI. The
      region around the PVs was divided into eight segments: roof, anterior-superior,
      anterior-carina, anterior-inferior, bottom, posterior-inferior, posterior-carina,
      and posterior-superior segment. The lesion width and lesion gap in each segment
      were compared between the two groups. Lesion gaps were defined as no-enhancement
      sites of >4 mm. Results: As compared to the RF group, the overall lesion width
      was significantly wider and lesion gaps significantly fewer at the anterior
      superior segment of the left PV (LAS) and anterior-inferior segment of the right
      PV (RAI) in the CB group (lesion width: 8.2 +/- 2.2 mm vs 5.6 +/- 2.0 mm, P =
      .001; lesion gap at LAS: 7% vs 38%, P = .02; lesion gap at RAI: 7% vs 46%, P =
      .006). Conclusions: The PVI lesions after CB ablation were characterized by
      extremely wider and more continuous lesions than those after RF ablation.

PMID- 29657592
TI  - Design and baseline characteristics of the Xarelto Post-Authorization Safety &
      Effectiveness Study in Japanese Patients with Atrial Fibrillation (XAPASS).
AB  - Background: The phase III Japanese Rivaroxaban Once-Daily Oral Direct Factor Xa
      Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and
      Embolism Trial in Atrial Fibrillation (J-ROCKET AF) showed that the rivaroxaban
      group had a lower event rate of intracranial bleeding than the warfarin group and
      that rivaroxaban was noninferior to warfarin for the principal safety outcome.
      However, safety and effectiveness data from unselected patients with AF in
      everyday clinical practice in Japan are lacking. Methods: The Xarelto Post
      Authorization Safety & Effectiveness Study in Japanese Patients with Atrial
      Fibrillation (XAPASS) is a real-world, prospective, single-arm, observational
      study mandated by the Japanese authority as postmarketing surveillance. XAPASS
      involves patients with nonvalvular AF prescribed rivaroxaban. The principal
      safety outcome is a composite of major and nonmajor bleeding events, and the
      primary effectiveness outcome is the incidence of ischemic stroke, hemorrhagic
      stroke, noncentral nervous system systemic embolism, and myocardial infarction.
      Results: In total, 11 308 patients were enrolled from April 2012 to June 2014.
      Their age was 73.1 +/- 9.9 years, and their CHADS 2 score was 2.2 +/- 1.3. Female
      patients, patients aged >=75 years, patients with a body weight of <=50 kg, and
      patients with a creatinine clearance of <50 mL/min constituted 38.1%, 48.7%,
      19.5%, and 23.9% of all patients, respectively. Almost half (53.2%) of patients
      were prescribed other anticoagulants before starting rivaroxaban. Conclusions:
      Data from this study will supplement those from the J-ROCKET AF and provide
      practical information for the optimal use of rivaroxaban for stroke prevention in
      Japanese patients with AF (Clinicaltrials.gov: NCT01582737).

PMID- 29657593
TI  - Not all rotors, effective ablation targets for nonparoxysmal atrial fibrillation,
      are included in areas suggested by conventional indirect indicators of atrial
      fibrillation drivers: ExTRa Mapping project.
AB  - Background: Effects of nonparoxysmal atrial fibrillation (non-PAF) ablation
      targeting complex fractionated atrial electrogram (CFAE) areas and/or low voltage
      areas (LVAs) are still controversial. Methods and Results: A recently developed
      online real-time phase mapping system (ExTRa Mapping) was used to conduct LVA
      mapping and simultaneous ExTRa and CFAE mapping in 28 non-PAF patients after
      pulmonary vein isolation (PVI). Nonpassively activated areas, in the form of
      meandering rotors and/or multiple wavelets assumed to contain non-PAF drivers,
      partly overlapped with CFAE/LVAs but not always coincided with them. Conclusion:
      Real-time rotor imaging, rather than conventional indirect indicators only, might
      be very useful for detecting non-PAF drivers.

PMID- 29657594
TI  - Clinical and echocardiographic response of apical vs nonapical right ventricular
      lead position in CRT: A meta-analysis.
AB  - Background: Traditionally the right ventricular (RV) pacing lead is placed in the
      RV apex in cardiac resynchronization therapy (CRT). It is not clear whether
      nonapical placement of the RV lead is associated with a better response to CRT.
      We aimed to perform a meta-analysis of all randomized controlled trials (RCTs)
      that compared apical and nonapical RV lead placement in CRT. Methods: We searched
      PubMed, EMBASE, Cochrane, Scopus, and relevant references for studies and
      performed meta-analysis using random effects model. Our main outcome measures
      were all-cause mortality, composite of death and heart failure hospitalization,
      improvement in ejection fraction (EF), left ventricle end-diastolic volume
      (LVEDV), left ventricle end-systolic volume (LVESV), and adverse events. Results:
      Seven RCTs with a total population of 1641 patients (1199 apical and 492
      nonapical) were included in our meta-analysis. There was no difference in all
      cause mortality (5% vs 4.3%, odds ratio (OR) = 0.86; 95% confidence interval (CI)
      0.45-1.64; P = .65; I2 = 11%) and a composite of death and heart failure
      hospitalization (14.2% vs 12.9%, OR = 0.92; 95% CI: 0.61-1.38; P = .68; I2 = 0)
      between apical and nonapical groups. No difference in improvement in EF (Weighted
      mean difference (WMD) = 0.37; 95% CI: -2.75-3.48; P = .82; I2 = 68%), change in
      LVEDV (WMD = 3.67; 95% CI: -4.86-12.20; P = .40; I2 = 89%) and LVESV (WMD = 
      1.20; 95% CI: -4.32-1.91; P = .45; I2 = 0) were noted between apical and
      nonapical groups. Proportion of patients achieving >15% improvement in EF was
      similar in both groups (OR = 0.85; 95% CI: 0.62-1.16; P = .31; I2 = 0).
      Conclusion: In patients with CRT, nonapical RV pacing is not associated with
      improved clinical and echocardiographic outcomes compared with RV apical pacing.

PMID- 29657595
TI  - A novel way to facilitate left ventricular lead implantation: Jailed catheter
      technique.
AB  - An important therapeutic modality for heart failure with left ventricular
      dyssynchrony, left ventricular lead placement, cannot be achieved due to anatomic
      challenges in some cases. In the current case, a novel implantation technique to
      overcome an anatomic difficulty, angled takeoff of the side branch of the
      coronary sinus, was presented.

PMID- 29657596
TI  - High defibrillation threshold with a subcutaneous implantable cardiac
      defibrillator due to the lead having been positioned in the fat layer.
AB  - A 46-year-old female with a body mass index of 38.9 kg/m2 and no organic heart
      disease underwent a subcutaneous implantable cardioverter-defibrillator
      implantation for secondary prevention of sudden cardiac death in the setting of
      idiopathic ventricular fibrillation. Defibrillation threshold (DFT) testing
      during implantation detected high shock impedance and high DFT. Fluoroscopy
      revealed subcoil fat between the lead and the sternum, which we suspected was the
      reason for the high shock impedance and high DFT. We repositioned the lead to a
      site just above the sternum and the shock impedance and DFT improved to within
      the respective normal ranges.

PMID- 29657586
TI  - European Heart Rhythm Association (EHRA)/Heart Rhythm Society (HRS)/Asia Pacific
      Heart Rhythm Society (APHRS)/Latin American Heart Rhythm Society (LAHRS) expert
      consensus on arrhythmias and cognitive function: What is the best practice?

PMID- 29657597
TI  - Successful catheter ablation of ventricular premature complexes from the right
      atrial side of the atrioventricular septum with good contact force.
AB  - The acquisition of good contact force for radiofrequency catheter ablation of
      ventricular premature complexes (VPCs) originating from the basal septum of the
      left ventricle (LV) is often difficult. We describe a case of VPCs originating
      from the basal septum of the LV, which were successfully eliminated by applying
      radiofrequency at the right atrium (RA) side of the atrioventricular septum (AVS)
      without causing any significant impairment of atrioventricular conduction because
      the ablation catheter could obtain better contact force through the RA approach.
      Moreover, intracardiac echocardiography (ICE) and RA angiography effectively
      demonstrated the AVS.

PMID- 29657598
TI  - Late Ratchet syndrome involving isolated left ventricular lead dislodgement post
      cardiac resynchronization therapy defibrillator generator change.
AB  - Lead dislodgement following cardiac implantable electronic device (CIED)
      generator change is rare. We report a case including the postulate mechanism of
      an isolated left ventricular lead dislodgement 3 months after cardiac
      resynchronization therapy defibrillator pulse generator change.

PMID- 29657600
TI  - Electrocardiographic "precordial pattern break sign" for posterior coronary
      venous system.

PMID- 29657599
TI  - Association between epicardial adipose tissue and coronary artery vasospasm
      during pulmonary vein isolation.
AB  - Coronary artery vasospasms (CAVs) during pulmonary vein isolation have been
      reported, but the mechanism remains unclear. We experienced a rare case of CAVs
      caused by radiofrequency (RF) applications to sites with massive epicardial
      adipose tissue (EAT) attached. Because EAT contains ganglionated plexuses, RF
      application may have caused an autonomic nervous system imbalance, which thereby
      provoked severe CAVs.

PMID- 29657601
TI  - Pin-port misconnection induced endless loop tachycardia.

PMID- 29657602
TI  - Guiding nanomaterials to tumors for breast cancer precision medicine: from tumor
      targeting small-molecule discovery to targeted nanodrug delivery.
AB  - Precision medicine emphasizes patient-specific formulation for treatment of
      diseases, especially cancer. However, in targeted cancer treatment, because the
      expression level of tumor receptors in each patient varies even for the same type
      of cancer, the ligand/receptor-mediated approach does not seem promising for
      precision medicine. In this work, we demonstrated our strategy of using a phage
      display technique for breast cancer precision medicine. Using in vivo biopanning,
      we first selected an MCF-7 breast tumor-targeting peptide, then tested the
      effectiveness of the as-selected peptide in tumor homing and finally conjugated
      the peptide to a model photothermal drug, namely, gold nanorods, to achieve
      enhanced cancer killing efficacy. The peptides identified by the phage display
      technique can guide the drug to the tumors without the need to know the exact
      receptors on the tumor. This approach requires significantly less effort to
      explore patient-specific targeting molecules for precision medicine.

PMID- 29657604
TI  - The role of intestinal ultrasound in diagnostics of bowel diseases.
AB  - Intestinal ultrasound is a safe and inexpensive method that allows visualisation
      of the gastrointestinal tract and detection of abnormalities. This examination
      involves the use of two different ultrasound transducers: a low-frequency convex
      probe and high-frequency linear probe. When needed, the performance of these
      methods can be enhanced by the use of contrast media or Doppler techniques.
      Intestinal ultrasound is mostly utilised for the diagnosis and follow-up of
      patients with inflammatory bowel diseases, helping to avoid frequent use of
      invasive and expensive diagnostic procedures and leading to early implementation
      of suitable treatment. This technique can also serve to detect other pathologic
      conditions that are present in the gastrointestinal tract. It is a promising
      method with high sensitivity and specificity, which has gained popularity in
      recent years and has the potential to become the method of choice in the
      diagnostics of many intestinal disorders.

PMID- 29657603
TI  - Impact of physical activity and exercise on male reproductive potential: a new
      assessment questionnaire.
AB  - Male athletes in general are subjected to the same causes of infertility as the
      general population, but sports practice itself may be possibly an additional
      infertility factor or, at least an aggravating factor for a previously existing
      fertility condition; on the contrary, being physically active has been
      hypothesized to favor hormonal and seminological processes and could be
      beneficial for fertility. In this relationship, the different inherent parameters
      of physical activity-exercise (training volume, intensity, objective,
      organization and frequency) are of paramount importance. Therefore, this review
      discusses both the negative and positive impact of physical exercise on the male
      reproductive potential. Clear knowledge is lacking on this topic as incongruences
      exist due to the fact that studies lack standardization in assessment tools or
      research protocols. So that future studies can reveal more information regarding
      exercising male fertility, we introduce a unique questionnaire developed with the
      intent to help standardize future studies on male fertility and exercise.

PMID- 29657605
TI  - Meta-analysis of the efficacy and safety of pantoprazole in the treatment and
      symptom relief of patients with gastroesophageal reflux disease - PAN-STAR.
AB  - Introduction: Proton pump inhibitors therapy success in the treatment of
      gastroesophageal reflux disease (GERD) is a difficult task because the extent of
      mucosal damage has no relation with the severity of the symptoms. Aim: To
      establish the efficacy of pantoprazole treatment in patients with erosive reflux
      disease (ERD) and in those with non-erosive reflux disease (NERD), by assessing
      symptom relief and quality of life. Treatment duration and adverse events
      associated with pantoprazole treatment were analysed. Material and methods: This
      meta-analysis was based on three multicentre, prospective, open-label, phase IV
      trials conducted in Slovenia, Poland, and the Russian Federation. In total, 252
      patients with GERD were included and treated with pantoprazole 40 mg once daily
      for 4 or 8 weeks, depending on the fulfilment of predefined healing criteria.
      Symptoms were assessed by patients on a scale from 0 to 3 and the quality of life
      on a rating scale from 1 to 10. Results: Forty-five percent of patients fulfilled
      the healing criteria after 4 weeks of treatment, and 70% of patients after 8
      weeks of treatment. Patients who failed to reach the healing criteria reported
      significant reduction of symptoms severity. The response to 8-week treatment was
      significantly higher in patients with ERD (76%) when compared to patients with
      NERD (64%). Discontinuation of treatment after 4 weeks was not associated with
      worsening of symptoms and did not affect quality of life. Pantoprazole treatment
      was associated with improvement of symptoms and the quality of life of GERD
      patients over 8 weeks of treatment and showed that GERD patients with persisting
      symptoms benefit from prolonging treatment to 8 weeks. Treatment with
      pantoprazole 40 mg was very well tolerated - more than 90% of patients were
      without adverse events throughout the whole study and only 4 patients
      discontinued the treatment due to adverse events related to pantoprazole
      treatment. Conclusions: Pantoprazole 40 mg was associated with complete relief of
      GERD-related symptoms in the majority of patients with ERD and NERD. Furthermore,
      the severity of symptoms was significantly reduced in patients without complete
      relief of symptoms. Pantoprazole also continuously improved the quality of life
      of GERD patients over 8 weeks of treatment and was very well tolerated throughout
      the whole study. Therefore, this meta-analysis suggests that pantoprazole 40 mg
      once daily is an effective and well-tolerated choice for providing symptom relief
      of patients with GERD.

PMID- 29657606
TI  - Early biliary drainage is associated with favourable outcomes in critically-ill
      patients with acute cholangitis.
AB  - Introduction: Acute cholangitis (AC) is a clinical condition that requires prompt
      medical management with IV fluids, antibiotics, and biliary drainage (BD). The
      optimal timing for BD remains unclear. Aim: To investigate the effect of biliary
      drainage timing on clinical outcomes in AC. Material and methods: We conducted a
      retrospective study of patients with AC admitted to the ICU using the
      Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC-III) database.
      Emergency department to BD time, hospital death, length of stay (LOS), and
      severity scores were extracted from the database. We investigated the effect of
      BD timing on mortality rates, persistent organ failure, and LOS. Results: A total
      of 177 patients were included; 50% were males; median age was 75 years, in
      hospital mortality was 9.6%, mean time-to-ERCP was 32 h (range: 0.42-229.6) with
      76% meeting the Tokyo Guidelines (TG13) criteria for severe cholangitis, and
      median Simplified Acute Physiology Score II (SAPS II) was 42 (IQR: 33-51). Using
      24 h as a cut-off, patients who underwent BD <= 24 h had less persistent organ
      failure (OR = 0.49; 95% CI: 0.26-0.96, p = 0.040), shorter ICU LOS (3.25 vs. 4.95
      days, p = 0.040), shorter hospital LOS (7.71 vs. 13.57 days, p = 0.001), but no
      difference in either in-hospital mortality (OR = 0.47, 95% CI: 0.17-1.29, p =
      0.146) or 28-day mortality (OR = 0.61, 95% CI: 0.24-1.53, p = 0.297).
      Conclusions: In critically-ill patients with acute cholangitis, early biliary
      drainage <= 24 h is associated with less persistent organ failure and shorter
      length of stay but had no effect on patient survival.

PMID- 29657607
TI  - Efficacy and safety of pegylated interferon alpha and ribavirin in patients
      monoinfected with HCV genotype 4.
AB  - Introduction: Dual therapy (PegIFN and ribavirin) (DT) was the standard of care
      in patients infected with HCV genotype 4 (HCV-4) until 2014. Nowadays, new
      treatment options are available including interferon (IFN)-based and other IFN
      free regimens. Aim: To assess the efficacy (SVR24) and safety of DT and the
      selected predictor factors of SVR in HCV-4 infected patients. Material and
      methods: One hundred and twelve patients (62 men) of median age 23 years were
      treated with DT for 48/72 weeks (107/5) in the years 2006-2014. Most of them were
      treatment naive (80.4%) and with fibrosis F <= 2 (83.1%). To select a subset of
      independent predictors of SVR Logistic Regression Analysis was applied. Results:
      SVR24 was achieved in 46/112 (41.1%) patients. The mean viral load was 5.55 log10
      IU/ml. Lack of therapy experience increases the odds of achieving SVR (OR = 4.17;
      1.04-16.67), whereas more advanced fibrosis and higher baseline viral load tend
      to decrease the probability of SVR (OR = 0.05; 0.01-0.52 and OR = 0.44; 0.17
      1.13, respectively). In contrast, the weight loss is associated with higher
      probability of virological response (OR = 4.31; 1.37-13.60). Two hundred and
      seventy-nine adverse events (AEs) were reported in 96 individuals. The rates and
      types of AEs were similar in patients treated with PegIFN-alpha2a/RBV and PegIFN
      alpha2b/RBV. Overall, 3 (2.7%) patients discontinued therapy prematurely because
      of serious AEs. Conclusions: SVR24 was low. Loss of weight was a new positive
      predictive factor of SVR found in our study. Most of the AEs were typical of
      those previously reported for DT.

PMID- 29657608
TI  - The use of endoscopic ultrasonography in the detection and differentiation of
      pathology in the wall of the upper gastrointestinal tract.
AB  - Introduction: The growing incidence of gastrointestinal diseases forces to
      improve imaging techniques. Identification of lesions located inside the wall of
      intestinal tract or in close proximity often was not possible using endoscopy or
      computed tomography. Aim: To assess the usefulness of endosonography (EUS) in the
      differentiation between compression from the outside and intramural lesions of
      the upper gastrointestinal tract. Material and methods: For 4 years 20,012
      patients with performed gastroscopies were enrolled in the study. One hundred and
      ninety-nine patients (96 females, 103 males; age 62.2 +/-14.1 years) with
      pathology of the wall of the upper gastrointestinal tract qualified for further
      diagnosis. Endosonography and computed tomography (CT) were performed in each
      patient. A chest CT was performed in patients with a lesion in the oesophagus. An
      abdomen CT was performed in patients with pathology in the stomach or duodenum.
      Based on the results of EUS, histopathology, and imaging, each patient qualified
      for treatment, endoscopic observation, surgery, or cancer treatment. Results: In
      EUS 129 (64.8%) intramural lesions were identified. Five (2.5%) diagnoses were
      false negative. In 62 (31.2%) patients no intramural changes were recognised and
      three (1.5%) results were false positive. The sensitivity and specificity of EUS
      was 96.3% and 95.4%, respectively, with positive predictive value 90.7%, negative
      predictive value 97.8%, and overall accuracy 95% (p < 0.05). Endoscopic therapy
      was performed in 31 (15.6%) patients, and 99 (49.8%) were classified for
      endoscopic observation. Surgery was performed in 50 (25.1%) patients, and 19
      (9.5%) patients required oncologic treatment. Conclusions: Endosonography exceeds
      computed tomography in differentiating compression from the outside and
      intramural lesions of the upper gastrointestinal tract.

PMID- 29657609
TI  - Translation to Polish, cross-cultural adaptation, and validation of the Bristol
      Stool Form Scale among healthcare professionals and patients.
AB  - Introduction: The seven-point Bristol Stool Form Scale (BSFS), which refers to
      seven pictures of different forms of stool, is a commonly used instrument to
      assess stool consistency. Aim: To translate, cross-culturally adapt, and validate
      the BSFS for its use in Poland. Material and methods: The steps included forward
      translation, reconciliation, backward translation, comparison of the two English
      versions and validation of the translation, pilot testing, proofreading, approval
      of the final version of the target language BSFS, and validation. The latter
      process involved healthcare professionals (physicians and nurses), healthy
      adults, and adult patients with gastrointestinal disorders, who were asked to
      correlate images of seven types of stools with their descriptions. All available
      subjects were asked to repeat the survey to assess test-retest reliability. The
      primary outcome measures were validity (accuracy) and reliability
      (repeatability). Results: A total of 320 subjects took part in the validation
      study (80/group). Overall, concordance between descriptions and pictures was
      78.7%, and the overall kappa index was good (0.75, 95% confidence interval (CI):
      0.73 to 0.77). Test-retest assessment was performed in 170 (53.1%) subjects
      within a mean interval of 5.9 +/-2.5 days. Overall, concordance between
      definitions and pictures for the re-testing phase was 90.7% with a kappa index of
      0.89 (95% CI: 0.87 to 0.91). Conclusions: As a result of the translation and
      cultural adaptation process, a final Polish version of the BSFS was created. The
      substantial validity and reliability of this Polish version was demonstrated.

PMID- 29657610
TI  - Detection of hepatocellular carcinoma by tissue resonance interaction method
      (TRIM).
AB  - Introduction: Diagnosis of hepatocellular carcinoma (HCC) is considerably
      delayed, being frequently done in the non-curative stage of disease. The reason
      for delayed diagnosis is indolent course in early stages and/or unspecific
      symptoms indistinguishable from underlying cirrhosis. Hitherto methods used for
      screening of HCC have important limitations. TRIMprob is a non-invasive method,
      which showed utility in detection of cancers located in prostate, breast, or
      urinary bladder. Aim: To determine the diagnostic accuracy of TRIMprob in
      detecting HCC in cirrhotic liver. Material and methods: Forty-five patients were
      prospectively enrolled according to final clinical diagnosis into a group of
      cirrhosis and HCC or a group of cirrhosis without HCC. A control group consisted
      of 33 healthy subjects. Hepatocellular carcinoma was diagnosed by computed
      tomography (CT) or magnetic resonance (MR) and guided biopsy. The TRIMprob
      examination was performed in each patient. Three wave frequencies were used: 465,
      930, and 1395 MHz. Results: In patients with HCC the intensity of return signal
      using wave a frequency of 465 MHz was significantly reduced in patients with HCC
      in comparison to healthy subjects (p < 0.0005), but not to cirrhotic patients
      without HCC. Moreover, cirrhosis was associated with significantly decreased
      TRIMprob signal in comparison to healthy liver (p < 0.002). In ROC analysis an
      optimal cut-off value for detection of HCC was 106 units, which yielded 80%
      sensitivity. Conclusions: TRIMprob identifies HCC with good sensitivity; however,
      the accuracy of this method to identify HCC in screening circumstances may be
      hindered by attenuation of the resonance interaction signal by cirrhosis itself.

PMID- 29657611
TI  - Gastric cancer with situs inversus totalis: does it really create difficulties
      for surgeons?
AB  - Introduction: Situs inversus totalis (SIT) is a very rare condition that is seen
      at a rate of one in about 6000-8000 births. Aim: To offer a general view on the
      coexistence of SIT and gastric cancer, accompanied by a literature review.
      Material and methods: Within the scope of this study, the case of a patient with
      gastric adenocarcinoma and SIT has been presented. Previous research on gastric
      cancer cases with SIT was reviewed through a comprehensive search of the PubMed,
      Medline, and Google Scholar databases. The keywords used to conduct this research
      were "situs inversus totalis and gastric cancer," "situs inversus totalis and
      gastric malignant," and "situs inversus totalis and gastric resection." The
      database search covered English studies published between 2000 and 2016. Results:
      The results of our literature review revealed 20 studies of patients with gastric
      cancer and SIT, and 21 related cases. Overall, 12 of the patients were male, 9
      were female, and their mean age was 61.8 +/-10.97 years. The vascular assessment
      data showed that three out of the 13 mentioned cases had vascular anomalies.
      Eleven of the patients had laparoscopic resections, and one of the patients that
      had a surgical procedure exhibiting a postoperative mechanical obstruction.
      Conclusions: The coexistence of SIT and gastric cancer is a very rare condition,
      and a careful preoperative radiological assessment should be conducted because
      there can be accompanying vascular anomalies. Laparoscopies and robotic surgeries
      can be performed for suitable patients at experienced centres, consistent with
      oncological principles.

PMID- 29657612
TI  - Deal a death blow! HCC in cirrhotics - thrombotic complications: their frequency,
      characteristics, and risk factors.
AB  - Introduction: The hepatocellular carcinoma (HCC), being the commonest primary
      cancer, holds the sixth slot in the list of common cancers worldwide. Thrombotic
      complications in the form of portal vein tumour thrombosis (PVTT) and bland
      portal vein thrombosis with HCC are common with a bad prognosis. Aim: The study
      aims to determine the demographic, clinical, and biochemical parameters of HCC
      patients. The study also compares the clinical and biochemical parameters among
      patients having HCC with and without thrombotic complication. It further aims to
      assess the risk factors for thrombotic complication. Material and methods: This
      was a retrospective study with a cross sectional design. Clinical and biochemical
      parameters among patients having HCC with and without thrombotic complication
      were determined. Tests of statistical significance were applied where a p-value <
      0.05 was statistically significant. Results: Overall 118/305 (38.7%) patients of
      HCC had thrombotic complications. Most of the patients (74.5%) had PVTT whereas
      in 25.5% bland PVT was found. Higher age, male gender, greater tumour size,
      advanced stage of HCC (Okuda II, III), multifocal/massive tumour morphology and
      presence of oesophageal varices, upper GI bleeding, ascites and hepatic
      encephalopathy, and extrahepatic spread were found to be statistically
      significant for thrombotic complication (p < 0.05 for each). Conclusions: Viral
      related HCC is a commonly reported problem. Thrombotic complication is mainly due
      to tumour thrombosis rather than bland portal vein thrombosis. Age, gender,
      greater tumour size, advanced stage of HCC (Okuda II, III), and
      multifocal/massive tumour morphology were important risk factors for thrombotic
      complication.

PMID- 29657613
TI  - Relationship between physician-based assessment of disease activity, quality of
      life, and costs of ulcerative colitis in Poland.
AB  - Introduction: Ulcerative colitis (UC) is an idiopathic inflammatory bowel
      disorder, which requires lifelong treatment. It generates substantial direct and
      indirect costs, and significantly affects the quality of life, especially in the
      active state of the disease. Aim: To evaluate the direct and indirect costs of UC
      as well as to assess disease activity and quality of life reported by patients
      with UC in Polish settings. Material and methods: A questionnaire, cross
      sectional study among UC patients as well as physicians involved in the therapy
      of the patients was conducted. The Clinical Activity Index (CAI) was used to
      assess disease activity, and the WPAI questionnaire to assess productivity loss.
      The quality of life was presented as utility calculated using the EQ-5D-3L
      questionnaire. Indirect costs included absenteeism, presenteeism, and informal
      care were assessed with the Human Capital Approach and expressed in euros (?).
      The productivity loss among informal caregivers was valuated with the average
      wage in Poland. Correlations were presented using the Spearman's coefficient, and
      the between-group difference was assessed with Mann-Whitney U-test. Results: One
      hundred and forty-seven patients participated in the study, including 95 working
      persons. Mean cost of absenteeism and presenteeism was ?1615.2 (95% CI: 669.5
      2561.0) and ?3684.4 (95% CI: 2367.8-5001.1), respectively, per year per patient
      with a disease in remission. The mean yearly cost of productivity loss due to
      informal care was estimated to be ?256.6 (range: 0.0-532.6). The corresponding
      values for patients with active disease were: ?8,913.3 (95% CI: 6223.3-11,603.3),
      ?4325.1 (95% CI: 2282.4-6367.8), and ?2396.1 (95% CI: 402.0-4390.3). The between
      group difference in total indirect costs, cost of absenteeism, and cost of
      informal care was statistically significant (p < 0.05). The average weighted
      monthly costs of therapy with particular drugs categories (e.g. mesalazine or
      biologic drugs) differed significantly between active disease or remission
      patients. The difference in utility values between patients with a disease in
      remission (0.898 +/-0.126) and patients with an active disease (0.646 +/-0.302)
      was statistically significant. Conclusions: Our study revealed the social burden
      of UC and high dependency of direct and indirect costs as well as quality of life
      on the severity of UC in Poland. The statistically significant differences were
      identified in total direct and indirect cost, cost of absenteeism, cost of
      informal care, and health-related quality of life among patients with an active
      disease compared to patients with a disease in remission.

PMID- 29657614
TI  - Acute pancreatitis in children.
AB  - Introduction: The acute pancreatitis is a rare disease, but it has started to be
      diagnosed more often in children. Aim: The aim of the study was single-centre,
      retrospective analysis of the incidence, aetiology, and clinical course of acute
      pancreatitis in children. Material and methods: We analysed the medical records
      of patients with acute pancreatitis hospitalised in the Gastroenterology Unit of
      the Paediatrics Department, Medical University of Silesia from Jan 2004 to Dec
      2013. Results: There were 76 cases of acute pancreatitis among 51 children
      (average age: 12.07 years) hospitalised in the Gastroenterology Unit between
      January 2004 and December 2013. The diagnosis of acute pancreatitis was performed
      on the basis of INSPIRE criteria and modified Atlanta classification. Patients
      were divided into groups: I - 1-12 years old, which included 20 (39.21%) children
      and II - 13-18 years old, with 31 (60.78%) children. The idiopathic aetiology was
      the most common cause of acute pancreatitis, occurring in 22 (43.1%) children,
      and in 15 cases the aetiology of the disease was biliary (29.4%). Genetically
      determined causes were diagnosed in 8 (15.7%) patients, the PRSS1 mutation in
      four patients, mutation in SPINK1 in 1 child, and CFTR gene mutation in 1 child.
      Two children simultaneously had two genes mutations (CFTR, SPINK1), and during
      the considered period had more than one episode of acute pancreatitis.
      Conclusions: Acute pancreatitis of idiopathic aetiology was most common among the
      examined children, and this should encourage the continued search for the causes
      of disease, especially genetic, and with particular emphasis on younger age
      group.

PMID- 29657615
TI  - KRAS, KIT and TP53 mutations in mother's and daughter's gastric cardia
      adenocarcinomas.

PMID- 29657616
TI  - Hereditary angioedema restricted to the digestive tract.

PMID- 29657617
TI  - Tackling Communication Breakdown - Clinically Unjustified Examinations Revisited.
AB  - A lack of communication between the referring clinician and radiologist leads to
      innumerable unnecessary examinations in the developed world, including Poland.
      Are the current administrative efforts reaching the right audience and what
      changes await us in the near future?

PMID- 29657618
TI  - Diffusion-Weighted Imaging and Color Doppler Ultrasound in Evaluation of Partial
      Testicular Torsion in Rat Model.
AB  - Background: To evaluate the utility of histogram analysis of apparent diffusion
      coefficient (ADC) in the diagnosis of incomplete testicular torsion.
      Material/Methods: Fourteen Wistar albino rats were randomly allocated into two
      groups. In group 1 (control), left testicles were kept outside for 45 seconds and
      then replaced, whereas left testicles were twisted by 360 degrees  in group 2.
      Four hours later, DWI was performed. After that, magnetic resonance imaging (MRI)
      and testicular color Doppler ultrasound (CDU) were performed by two radiologists
      who looked for the presence or absence of blood flow. ADC measurements were
      carried out by two radiologists who were blinded to each other's measurements.
      After CDU, testes were surgically removed and a pathological examination was
      performed after four hours of torsion. Comparisons of minimum, mean, and maximum
      ADC values in testicles were performed with the Wilcoxon test. P value of 0.05 or
      less was considered as statistically significant. Inter-observer agreement was
      also analyzed. Results: In the torsion group, minimum ADC values for left
      testicles were significantly lower than for the control group (p<0.05),
      regardless of the observer. Inter-observer agreement for measurements of ADCmin
      and ADCmax values was substantial, with an ICC score of 0.751 and 0.774,
      respectively (95% CI). Inter-observer agreement for the measurement of ADCmean
      value was excellent, with an ICC score of 0.844 (95% CI). The pathological
      examination revealed mild interstitial edema and closely packed seminiferous
      tubules in the left testes, indicating reversible damage in the torsion group.
      Conclusions: On the pathological examination, all left testes in the torsion
      group were recoverable after four hours of torsion. Minimum ADC values can be
      used as an auxiliary method in the diagnosis of partial testicular torsion.
      Comparing minimum ADC values between the affected and non-affected testicles can
      be a useful tool in the early diagnosis of incomplete testicular torsion.

PMID- 29657619
TI  - Extremely Rare Case of Bilateral Pure Primary Non-Gestational Ovarian
      Choriocarcinoma.
AB  - Background: Germ cell tumors of the ovary constitute less than one percent of
      ovarian tumors worldwide. Choriocarcinoma arising de novo from the ovary is very
      rare and only occasionally reported in the literature. Herein, we report a case
      of bilateral non-gestational pure primary ovarian choriocarcinoma that was
      confirmed by beta human chorionic gonadotropin (beta-HCG) levels and
      histopathology. Case Report: Our case is of a middle-aged multiparous female who
      presented with amenorrhea for three months. She underwent an evaluation with
      ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI),
      which revealed bilateral bulky solid adnexal masses. Based on an increased blood
      level of the beta human chorionic gonadotropin and a histopathological
      examination, the diagnosis of bilateral non-gestational pure primary ovarian
      choriocarcinoma was made. Conclusions: The imaging findings were found to be
      specific for bilateral non-gestational pure primary ovarian choriocarcinoma.

PMID- 29657620
TI  - Characteristic Multimodal Imaging of Medication-Related Osteonecrosis of the Jaw:
      Comparison Between Oral and Parenteral Routes of Medication Administration.
AB  - Background: To assess multimodal imaging features of medication-related
      osteonecrosis of the jaw (MRONJ) and to analyze the differences between oral and
      parenteral routes of medication administration. We retrospectively reviewed
      panoramic radiographs, CT, MRI, and bone scintigraphy of patients with MRONJ.
      Material/Methods: A retrospective study was conducted in 16 patients with MRONJ
      who underwent panoramic radiography, CT, MRI, and bone scintigraphy. Statistical
      analysis for the comparison between routes of medication administration and
      multimodal imaging features was performed with the Pearson's chi2 test. Results:
      The percentage of cases with sequestrum separation was 25.0% (4/16 cases) on
      panoramic radiography and 81.3% (13/16 cases) on CT. The percentage of cases with
      periosteal bone proliferation on CT was 41.7% (5/12 cases) in the oral route of
      administration vs. 100% (4/4 cases) in the parenteral route of administration
      (p=0.042). The percentage of cases with spread of soft tissue inflammation to
      buccal and other spaces on CT and MRI was 33.3% (4/12 cases) in the oral route of
      administration vs. 100% (4/4 cases) in the parenteral route of administration
      (p=0.021). Conclusions: The sequestrum separation on panoramic radiography in
      patients with MRONJ was unclear in comparison to CT. Furthermore, characteristic
      CT findings of patients with MRONJ in the parenteral administration group were
      periosteal bone proliferation and spread of soft tissue inflammation to buccal
      and other spaces.

PMID- 29657621
TI  - Diffusion-Weighted Imaging in the Oral and Maxillofacial Region: Usefulness of
      Apparent Diffusion Coefficient Maps and Maximum Intensity Projection for
      Characterization of Normal Structures and Lesions.
AB  - Background: The aim of this study was to investigate diffusion-weighted imaging
      (DWI) in the oral and maxillofacial region, with a special focus on the
      usefulness of apparent diffusion coefficient (ADC) maps and maximum intensity
      projection (MIP) for characterization of normal structures and lesions.
      Material/Methods: Thirty-five patients who underwent magnetic resonance imaging
      (MRI) for diagnosis of oral and maxillofacial lesions were included in this
      prospective study. DWI was performed on a 1.5 T unit, with b factor of 0 and 800
      s/mm2; moreover, ADC maps were generated. ADC values were measured for normal
      structures, odontogenic infections, squamous cell carcinomas (SCC), and
      hemangiomas. Results: As regards the normal structures, the mean ADC value of the
      cerebrospinal fluid (3.65+/-0.60*10-3 mm2/s) in the upper neck area was higher
      than that of the spinal cord (0.74+/-0.15*10-3 mm2/s, P=0.000), lymph nodes
      (0.87+/-0.17*10-3 mm2/s, P=0.000), and Waldeyer's ring (0.92+/-0.29*10-3 mm2/s,
      P=0.000). The mean ADC value of hemangiomas (1.52+/-0.31*10-3 mm2/s) was higher
      than that of odontogenic infections (0.85+/-0.36*10-3 mm2/s, P=0.034) and SCC
      (1.38+/-0.22*10-3 mm2/s, P=0.840). Furthermore, MIP (DWI) showed the normal
      structures and lesions in the oral and maxillofacial region in an improved way.
      Conclusions: DWI, ADC maps, and MIP can be used to characterize and differentiate
      normal structures and lesions in the oral and maxillofacial region.

PMID- 29657622
TI  - Computed Tomography Assessment of Hepatic Metastases of Breast Cancer with
      Revised Response Evaluation Criteria in Solid Tumors (RECIST) Criteria (Version
      1.1): Inter-Observer Agreement.
AB  - Background: To assess inter-observer agreement of revised RECIST criteria
      (version 1.1) for computed tomography assessment of hepatic metastases of breast
      cancer. Material/Methods: A prospective study was conducted in 28 female patients
      with breast cancer and with at least one measurable metastatic lesion in the
      liver that was treated with 3 cycles of anthracycline-based chemotherapy. All
      patients underwent computed tomography of the abdomen with 64-row multi- detector
      CT at baseline and after 3 cycles of chemotherapy for response assessment. Image
      analysis was performed by 2 observers, based on the RECIST criteria (version
      1.1). Results: Computed tomography revealed partial response of hepatic
      metastases in 7 patients (25%) by one observer and in 10 patients (35.7%) by the
      other observer, with good inter-observer agreement (k=0.75, percent agreement of
      89.29%). Stable disease was detected in 19 patients (67.8%) by one observer and
      in 16 patients (57.1%) by the other observer, with good agreement (k=0.774,
      percent agreement of 89.29%). Progressive disease was detected in 2 patients
      (7.2%) by both observers, with perfect agreement (k=1, percent agreement of
      100%). The overall inter-observer agreement in the CT-based response assessment
      of hepatic metastasis between the two observers was good (k=0.793, percent
      agreement of 89.29%). Conclusions: We concluded that computed tomography is a
      reliable and reproducible imaging modality for response assessment of hepatic
      metastases of breast cancer according to the RECIST criteria (version 1.1).

PMID- 29657623
TI  - Detailed Imaging Findings in a Rare Case of Kimura Disease, with Special Mention
      on Diffusion Weighted Imaging.
AB  - Background: Kimura disease is an uncommon, benign, chronic, idiopathic disease
      that is seen mainly in the Asian population, particularly in females. It mainly
      affects the salivary glands and in particular parotid and cervical lymph nodes.
      So far, the diagnosis of Kimura disease has been based on histopathology. We
      hereby report of a confirmed case of Kimura disease and provide a detailed
      explanation of its imaging features with a special emphasis on diffusion-weighted
      imaging, as diffusion sequences may help distinguish Kimura disease from
      malignancy. Case Report: A middle-aged female patient presenting with a history
      of multiple chronic neck swellings was thoroughly evaluated by ultrasound (US),
      computed tomography (CT), and magnetic resonance imaging (MRI). The imaging
      findings included gross enlargement of the left parotid gland, a focal lesion in
      the right parotid gland, and cervical lymphadenopathy. These features correlated
      with histopathological findings, and the diagnosis of Kimura disease was made.
      Conclusions: The imaging findings were found to be specific for Kimura disease.

PMID- 29657624
TI  - Unilateral Primary Adrenal B-Cell Lymphoma Clinically Mimicking Chronic
      Gastritis.
AB  - Background: Primary adrenal lymphomas are a very rare type of extranodal
      lymphoma, and they usually are found bilaterally. Symptoms of the disease are
      variable and depend on the type of lymphoma and/ or presence of adrenal
      insufficiency. Magnetic resonance imaging is the best radiologic modality for
      differentiating lymphomas from other adrenal malignancies; however,
      histopathology is considered as the gold standard method for diagnosing
      extranodal lymphomas. Case Report: We present a case of unilateral adrenal
      lymphoma that was initially diagnosed as an infectious disease and chronic
      gastritis, based on clinical and laboratory findings. Ultrasonography detected an
      adrenal mass, and magnetic resonance imaging excluded common lesions of the
      adrenal gland and showed lymphadenopathy around the major vessels of the abdomen.
      A percutaneous biopsy of the mass and bone marrow biopsy confirmed the diagnosis
      of primary adrenal lymphoma without bone marrow metastasis. Conclusions:
      Extranodal lymphomas can occur in almost every organ, and if nonspecific clinical
      findings are combined with the presence of a solid organ mass, lymphoma should be
      included in the differential diagnosis.

PMID- 29657625
TI  - Poland Syndrome with Ipsilateral Hypoplasia of Gluteal Muscles and Contralateral
      Hidradenitis Suppurativa.
AB  - Background: Poland syndrome (PS) is a rare congenital anomaly associated with
      absent or hypoplastic pectoralis major muscle and a wide spectrum of ipsilateral
      thoracic and upper extremity deformities. Hidradenitis suppurativa (HS) is a
      recurrent inflammatory follicular disease that commonly affects the apocrine
      bearing skin and involves follicular occlusion and hyperkeratosis. Case Report:
      We report a case of a 46-year-old male with a history of chronic recurrent
      hidradenitis suppurativa who was incidentally found to have a simple type of
      Poland syndrome with incidental hypoplasia of ipsilateral gluteal muscles.
      Conclusions: Not only can PS present with HS, which we describe for the first
      time, but it is also associated with a wide variability of symptoms such as
      previously unknown co-existence of gluteal muscles hypoplasia.

PMID- 29657626
TI  - A Rare Case of Caudal Regression Syndrome in a Foetus of Non-Diabetic Mother: A
      Case Report.
AB  - Backgound: Caudal regression syndrome (CRS) is an uncommon disorder in which
      there is abnormal development of the caudal end of the foetal spine along with
      many associated anomalies. Manifestations of this syndrome can vary from the
      absence of a few terminal coccygeal segments to complete lumbosacral agenesis.
      Its overall incidence is 1 in 60000 live births. It is more commonly seen in
      infants of diabetic mothers, with a 200-fold increased risk as compared to the
      general population. Case Report: We present a case of CRS in a foetus of a non
      diabetic mother and discuss the role of radiology in early diagnosis and timely
      management. We also correlate initial abnormalities of the nervous system found
      on imaging with postnatal clinical deficits. Conclusions: This case highlights
      the rarity caudal regression syndrome in a foetus of a non-diabetic mother. Early
      diagnosis of CRS is important for appropriate management.

PMID- 29657627
TI  - Acute Chest Pain of Coronary Origin in Patients without Diabetes: How
      Multidetector Computed Tomography (MDCT) Angiography Helps in Diagnosis.
AB  - Background: To assess the diagnostic value of MDCT coronary angiography for
      evaluation of acute chest pain of coronary origin in non-diabetic patients.
      Material/Methods: In 22 patients without DM, we assessed coronary arteries with
      multidetector CT angiography and invasive conventional angiography. Results: CT
      coronary angiography revealed positive coronary artery disease findings in 16
      patients; LAD was affected in 16 (72.3%), RCA in 14 (63.3%), and LCX in 8 (36.4%)
      cases. The proximal part of LAD was the most commonly affected coronary artery
      (14 cases, 63.3%) in the studied patients who underwent MSCT coronary
      angiography. As regards the calcium score, 4 patients (18%) had low calcium
      scores, 6 cases (27%) had moderate calcium scores, and 12 cases (55%) had high
      calcium scores. There were 6 patients with positive findings of coronary artery
      disease detected on MDCT coronary angiography that were not mirrored by
      conventional angiography. Conclusions: MDCT angiography of the coronaries is a
      good and rapid method for evaluation of the coronary anatomy and for early
      detection and grading of coronary lesions in non-diabetic patients.

PMID- 29657628
TI  - Accuracy of Ultrasonography (US) and Magnetic Resonance Imaging (MRI) in
      Detection of Rotator Cuff Tears in District General Hospital.
AB  - Background: Rotator cuff tears (RCTs) represent a significant proportion of
      shoulder diseases, hence they are a frequent cause of patient visits in shoulder
      clinics. However, the diagnosis of rotator cuff tears is controversial.
      Investigation of cuff tears is based on ultrasonography (US) and magnetic
      resonance imaging (MRI). Both modalities have been in use for decades, and their
      advantages and limitations are known. A recent Cochrane review of the subject
      suggested that US and MRI both performed well with respect to full thickness
      rotator cuff tears (FTT). However, they were less accurate with respect to
      partial thickness tears (PTT). The aim of this study is to assess the accuracy of
      US and MRI in diagnosing rotator cuff tears. Material/Methods: This is a
      retrospective analysis of a cohort of 255 patients who underwent shoulder
      arthroscopy. Of them, 125 patients had preoperative US, and 130 had preoperative
      MRI. The imaging results were compared with arthroscopic findings for patient.
      Results: After calculating sensitivity, specificity, positive prediction value
      (PPV), and negative prediction value, we found no statistically significant
      difference between US and MRI in detection of rotator cuff tears of any type
      (RCT) or FTT. However, US is more specific in detecting PTT compared to MRI
      (P=0.00008) but with no significant difference in other parameters. Conclusions:
      We concluded that US and MRI both have similar accuracy in diagnosing RCT of any
      sort and FTT. However, US is more specific than MRI in detecting PTT. In our
      institute, we now recommend US as the investigation of choice for diagnosing
      rotator cuff tears.

PMID- 29657629
TI  - Magnetic Resonance (MR) Imaging Assessment for Glossopharyngeal Neuralgia: Value
      of Three-Dimensional T2-Reversed MR Imaging (3D-T2R) in Conjunction with Other
      Modes of 3D MR Imaging.
AB  - Background: To retrospectively examine the usefulness of gray-scale reversal
      imaging of T2-weighted images (3D-T2R) in conjunction with other modes of 3D MRI
      for preoperative assessments in patients with glossopharyngeal neuralgia (GPN)
      due to neurovascular compression. Material/Methods: Imaging findings on 3D-T2R,
      constructive interference in steady state (CISS), and MRA were analyzed with
      reference to operative charts in 10 patients with GPN. Results: Offending vessels
      were associated with the posterior inferior cerebellar artery (PICA) in 9 of 10
      patients (90%). Eight of the 10 patients (80%) had offending vessels located at
      the supraolivary fossette. Of those eight patients, six (75%) had a shift of the
      ipsilateral vertebral artery to the affected side. Five (42%) and seven (48%)
      contact points were associated with the root entry/exit zone and the peripheral
      nerve system segment, respectively. In six of nine contact points (67%), 3D-T2R
      demonstrated the pathomorphological features at the contact points better than
      CISS. Conclusions: The offending vessels were mostly associated with posterior
      inferior cerebellar arteries, were frequently located at the supraolivary
      fossette, and had attachments at the root entry/exit zone and at the peripheral
      segment of the glossopharyngeal nerve, which was well demonstrated on 3D-T2R.

PMID- 29657630
TI  - Multidetector Computed Tomography (CT) in Evaluation of Congenital Cyanotic Heart
      Diseases.
AB  - Background: The aim of the study is to emphasize the role of 128 MSCT angiography
      in the diagnosis of congenital cyanotic heart diseases. Material/Methods: This
      study included sixty patients and was conducted from December 2014 to July 2016
      in the Multidetector CT unit of Zagazig University hospitals. All images included
      axial, MPR, MIP, and VRT and were interpreted in one session. Pulmonary veins
      were assessed for PAPVR or TAPVR, PDA, cardiac apex and heart chambers,
      interatrial or interventricular septal defects, pericardium, and site and size of
      the great veins (IVC and SVC). Results: This study included 60 patients. Thirty
      four were boys (56.7%), and 26 were girls (43.3%). The age ranged from nine
      months to five years, and the mean age was 34.5 months. We found the following
      anomalies: tetralogy of Fallot (15 patients, 25%), tricuspid atresia (12
      patients, 20%), Ebstein's anomaly (4 patients, 6.5%), pulmonic atresia or
      stenosis (7 patients, 11.5%), truncus arteriosus (6 patients, 10%), TGA (10
      patients, 17%), and TAPVR (6 patients, 10%). Conclusions: MDCT proved to be an
      important modality for decision-making in patients with congenital cyanotic heart
      diseases.

PMID- 29657631
TI  - Internal Mammary Artery Anastomoses in Patients without Breast Lesions (BIRADS 1)
      and in Patients with Malignant Breast Lesions (BIRADS 6) on Magnetic Resonance
      Imaging (MRI).
AB  - Background: We aimed to compare the frequency of IMA (internal mammarian artery)
      anastomoses in right and left breasts in patients without breast lesions and in
      patients with malignant breast lesions. Material/Methods: A total of 100 patients
      with no breast lesions and a total of 100 patients with malignant breast lesions
      were included in the study. The anastomoses of IMA of right and left breasts were
      evaluated on MIP and post-contrast T1-weighted magnetic resonance imaging (MRI)
      sequences. Breast MRI scans were read by a radiologist. Results: In patients with
      no breast lesions, IMA anastomoses were found in 45% of cases, and in patients
      with malignant breast lesions, IMA anastomoses were found in 58% cases. In four
      patients with malignant lesions, ipsilateral IMA was rudimentary, and the lesion
      was feeding from the contralateral IMA. Conclusions: No statistically significant
      difference was found between patients without any breast lesions and patients
      with malignant breast lesions with respect to the frequency of IMA anastomoses in
      right and left breasts. The frequencies were higher than expected in both groups.

PMID- 29657632
TI  - Real-Time Elastography for Differentiation of Breast Lesions.
AB  - Backroung: To investigate the diagnostic performance of the elastography-based
      strain index ratio in the differential diagnosis of malignant and benign breast
      lesions. Material/Methods: Seventy-nine breast masses that were classified as BI
      RADS category 3, 4, and 5 on B-mode ultrasonography (US) were further
      prospectively evaluated by real-time sonoelastography (RTE). To obtain an optimal
      cut-off value of the strain ratio for differentiating between malignant and
      benign breast lesions, RTE findings were compared with histopathology of core
      needle biopsy samples or with ultrasound follow-up data of the analyzed masses.
      Results: Seventy-nine breast lesions [BI-RADS category 3 (n=15), BI-RADS category
      4 (n=34), and BI-RADS category 5 (n=30)] were classified as malignant (n=36) or
      benign (n=43). The mean strain index value was 6.59+/-3.44 (range 0.6-14) for
      malignant lesions and 2.79+/-2.16 (range 0.6-8.7) for benign lesions,
      respectively (p<0.05). As regards the detection of malignant lesions, US was
      characterized by sensitivity and specificity of 100% (CI 95%; 88-100) and 90% (CI
      95%; 76-97), respectively. When an optimal value of the strain ratio (4.25) was
      obtained by ROC curve analysis, the sensitivity and specificity for diagnosing
      malignant lesions were 86% (CI 95%; 70-95) and 76% (CI 95%; 60-87), respectively.
      Conclusions: RTE can play an important role in the differentiation between
      malignant and benign breast masses, but it should be used in conjunction with
      ultrasonography.

PMID- 29657633
TI  - Magnetic Resonance Imaging (MRI) of Snapping Scapula in a 10-Year-Old Boy.
AB  - Background: Snapping scapula syndrome, also known as scapulothoracic crepitus or
      bursitis, is a manifestation of a mechanical abnormality of the scapulothoracic
      joint. In addition to characteristic findings on physical examination, magnetic
      resonance imaging (MRI) exquisitely reveals soft tissue changes such as muscle
      edema and scapulothoracic bursitis. Case Report: We present a case of a 10-year
      old boy who had snapping scapula syndrome of the right scapula that was
      associated with edema of the serratus anterior muscle at the scapulothoracic
      interface and with scapulothoracic, specifically supraserratus, bursitis on MRI.
      Conclusions: MRI in snapping scapula syndrome, which is a clinical diagnosis,
      exquisitely reveals soft tissue changes such as muscle edema and scapulothoracic
      bursitis. Such soft tissue findings of snapping scapula syndrome need to be kept
      in mind while evaluating routine shoulder and/or scapular region MRI, especially
      in the absence of relevant clinical information at the time of the imaging study.

PMID- 29657634
TI  - Assessment of the Pancreas with Strain Elastography in Healthy Children:
      Correlates and Clinical Implications.
AB  - Background: To determine strain index (SI) values at various locations in the
      pancreas and to investigate the relationship between age, gender, body weight,
      height, body mass index (BMI), and elasticity values of the pancreas in healthy
      children. Material/Methods: This cross-sectional trial was performed in 147
      healthy children who underwent transabdominal ultrasonography for strain
      elastography of the pancreas. A convex, 3.5-5-MHz probe was used to obtain the
      images. Baseline descriptive data including age (months), body weight (kg),
      height (cm), and BMI (kg/m2) were noted. Strain index values were calculated for
      the head, body, and tail of the pancreas, and a mean value was obtained. The
      relationship between demographic variables and SI values was assessed.
      Correlation between variables with normal distribution was evaluated with
      Pearson's correlation coefficient and Spearman's rho. Results: The average SI
      values in girls and boys were 1.30+/-0.34 and 1.32+/-0.22, respectively. There
      was no significant difference between SI values measured in the head, trunk, and
      tail of the pancreas (p=0.594). The average SI value did not differ between girls
      and boys (p=0.751). Correlation analysis revealed that SI was positively
      associated with age (p=0.005), body weight (p=0.004), height (p=0.003), and BMI
      (p=0.005). Conclusions: This study determined normal elasticity values of the
      pancreas in healthy children. SI values of pancreas change with age, body weight,
      height, and BMI in the pediatric population. Information obtained from healthy
      children can serve as a baseline against which pancreatic diseases can be
      examined.

PMID- 29657635
TI  - Ultrasound is Not Useful as a Screening Tool for Dengue Fever.
AB  - Background: Dengue fever is a tropical disease that is transmitted by female
      Aedes Aegypti mosquitos. Early diagnosis is necessary to reduce the mortality and
      morbidity associated with the disease. A combination of clinical, laboratory, and
      sonography findings can be potentially helpful in making an early diagnosis of
      dengue fever. There is paucity of literature on the use of ultrasound for dengue
      fever screening; hence, the primary objective of the study was to evaluate the
      utility of ultrasound as a screening tool in dengue fever. Material/Methods: A
      total of 160 patients of suspected dengue fever were included in the study. They
      underwent ultrasound examinations in order to search for thickening of the
      gallbladder wall, pleural effusion, and ascites. On the basis of ultrasound
      findings, 65 cases were positive and 95 cases were negative for dengue fever.
      Serological tests were also used for diagnosing dengue fever, 93 cases were
      seropositive and 67 cases were seronegative. The ultrasonically diagnosed cases
      were compared with serologically diagnosed cases, and appropriate descriptive
      statistical analyses were applied. Results: The ultrasound findings included gall
      bladder wall thickening in 66 patients (41.2%). The sensitivity, specificity, and
      positive predictive value of ultrasound in diagnosing dengue fever were 58%, 84%,
      and 83%, respectively. The negative predictive value and accuracy were 59% and
      68.8%, respectively. Conclusions: The present study suggests that increased gall
      bladder wall thickness, pleural effusion, ascites, hepatomegaly, and splenomegaly
      are highly suggestive of dengue fever in clinically suspected cases. However,
      ultrasound should not be used as a screening tool, as negative ultrasound
      findings cannot rule out dengue fever due to the low sensitivity of this
      examination.

PMID- 29657636
TI  - Lumbar Opening Pressure and Radiologic Scoring in Idiopathic Intracranial
      Hypertension: Is There Any Correlation?
AB  - Background: To investigate correlation between lumbar opening pressure (LOP) and
      radiological scores based on cranial MRI and contrast-enhanced MR venography in
      patients with idiopathic intracranial hypertension (IIH). Material/Methods:
      Patients with IIH who underwent brain MRI and contrast-enhanced MR venography
      before measurement of LOP between 2010-2014 were evaluated retrospectively. Three
      experienced radiologists (blinded to LOP values) evaluated a total of 51
      patients. They reached a consensus on the presence or absence of 6 radiological
      findings identified in the literature as characteristic for IIH: empty sella,
      perioptic dilation, optical tortuosity, flattening of the posterior globe,
      swelling of the optic disc, and bilateral transverse sinus stenosis. The
      radiological score was obtained by giving 1 point for the presence of each
      finding, with the highest possible score of 6 points. The correlation between the
      calculated radiological scores and LOP was evaluated. Results: There was no
      significant correlation between LOP and radiological scores (r=0.095; p=0.525,
      Spearman's rank coefficient). Similarly, no significant correlation was detected
      between LOP and each of the radiological findings (partial empty sella [p=0.137],
      perioptic dilation [p=0.265], optical tortuosity [p=0.948], flattening of the
      posterior globe [p=0.491], swelling of the optic disc [p=0.881], and bilateral
      dural sinus stenosis [p=0.837], Mann-Whitney U test). Conclusions: There was no
      significant correlation between LOP and reliable radiological features of IIH.

PMID- 29657637
TI  - Can Pixel Value Ratio be Used in the Assessment of Ceramic Bone Substitute
      Incorporation? Observations from a Pilot Study.
AB  - Background: Assessment of bone graft substitute incorporation is critical in the
      clinical decision making process and requires special investigations. We examined
      if the pixel value ratio (PVR) obtained in routine follow-up digital radiographs
      could be used for such assessment. Material/Methods: Radiographic images were
      acquired using either computed radiography or flat panel digital radiography
      systems. The PVR from radiographs of thirty children with ceramic bone substitute
      grafting were analyzed using the software from the picture archival and
      communication system (PACS) workstation. Graft incorporation was also assessed
      using the van Hemert scale. Three independent observers (A, B, C) measured PVRs
      at two different time points during the first and the last follow-up visits. PVR
      was compared with the van Hemert scale scores and analyzed using Spearman's rank
      correlation. Results: The mean intra-observer reliability was 0.8996, and inter
      observer reliabilities were 0.69 (A vs. C), 0.78 (A vs. B), and 0.85 (B vs. C)
      for the first follow-up visit and 0.74 (A vs. C), 0.82 (A vs. B), and 0.70 (B vs.
      C) for the last follow-up measurements. Spearman's correlation showed a strong
      negative association between PVR values and van Hemert scale scores, as the
      healing process advanced on serial measurements at each follow-up (r=-0.94, n=60,
      z=-7.24, p<=0.0001). The reliability of the PVR measurements was assessed using
      an aluminum step wedge and ceramic graft. Conclusions: PVR is potentially a
      reliable indicator of bone graft incorporation and can aid in clinical decision
      making provided standard radiographic techniques are used.

PMID- 29657638
TI  - Diagnostic Performance of Multidetector Computed Tomography (MDCT) in Diagnosis
      of Sinus Variations.
AB  - Background: In this prospective study, we looked for correlations between
      anatomic variants of paranasal sinuses and chronic or recurrent sinusitis.
      Material/Methods: Two hundred and forty (240) patients with clinical features of
      chronic rhinosinusitis were examined; patients with first-onset or allergic
      sinusitis and pregnant females were excluded. Routine multi-slice CT of the
      paranasal sinuses was performed to look for mucosal disease of the paranasal
      sinuses, drainage pathways, and presence of anatomical variations and their
      relation to known sinus drainage pathways. Results: Anatomic variations were very
      frequent, and we classified them into four easily recognized groups: nasal septum
      variations, middle turbinate variations, uncinate process variations, and
      ethmoidal variations. Deviated nasal septum was the most frequent variation in
      patients with chronic or recurrent sinusitis, and it was detected in 48.8% of
      cases. Agger nasi cells and concha bullosa were equally frequent (30.6%), and
      Haller cells were detected in 11.2%. Uncinate process variations were detected in
      18.1%, and the large ethmoid bulla was detected in 10%. Conclusions: The
      importance of anatomic variations is that they can compromise drainage pathway of
      the related sinus, which results in inflammatory sinus disease. Anatomical
      variations are not diseases on their own and may be present as incidental
      findings in patient with chronic sinusitis.

PMID- 29657640
TI  - Evaluation of Imaging Methods in Tick-Borne Encephalitis.
AB  - Tick-borne encephalitis (TBE) is caused by a virus that belongs to the
      Flaviviridae family and is transmitted by tick bites. The disease has a biphasic
      course. Diagnosis is based on laboratory examinations because of non-specific
      clinical features, which usually entails the detection of specific IgM antibodies
      in either blood or cerebrospinal fluid that appear in the second phase of the
      disease. Neurological symptoms, time course of the disease, and imaging findings
      are multifaceted. During the second phase of the disease, after the onset of
      neurological symptoms, magnetic resonance imaging (MRI) abnormalities are
      observed in a limited number of cases. However, imaging features may aid in
      predicting the prognosis of the disease.

PMID- 29657639
TI  - Magnetic Resonance (MR) Imaging of Vascular Malformations.
AB  - Vascular malformations pose a diagnostic and therapeutic challenge due to the
      broad differential diagnosis as well as common utilization of inadequate or
      inaccurate classification systems among healthcare providers. Therapeutic
      approaches to these lesions vary based on the type, size, and extent of the
      vascular anomaly, necessitating accurate diagnosis and classification. Magnetic
      resonance (MR) imaging (MRI) is an effective modality for classifying vascular
      anomalies due to its ability to delineate the extent and anatomic relationship of
      the malformation to adjacent structures. In addition to anatomical mapping, the
      complete evaluation of vascular anomalies includes hemodynamic characterization.
      Dynamic time-resolved contrast-enhanced MR angiography provides information
      regarding hemodynamics of vascular anomalies, differentiating high- and low-flow
      vascular malformations. Radiologists must identify the MRI features of vascular
      malformations for better diagnosis and classification.

PMID- 29657641
TI  - Top 50 Highly Cited Articles on Dual Energy Computed Tomography (DECT) in
      Abdominal Radiology: A Bibliometric Analysis.
AB  - This study aims to identify the 50 most highly cited articles on dual energy
      computed tomography (DECT) in abdominal radiology Thomson Reuters Web of Science
      All Databases was queried without year or language restriction. Only original
      research articles with a primary focus on abdominal radiology using DECT were
      selected. Review articles, meta-analyses, and studies without human subjects were
      excluded. Fifty articles with the highest average yearly citation were
      identified. These articles were published between 2007 and 2017 in 12 journals,
      with the most in Radiology (12 articles). Articles had a median of 7 authors,
      with all first authors but one primarily affiliated to radiology departments. The
      United States of America produced the most articles (16), followed by Germany (13
      articles), and China (7 articles). Most studies used Dual Source DECT technology
      (35 articles), followed by Rapid Kilovoltage Switching (14 articles), and
      Sequential Scanning (1 article). The top three scanned organs were the liver
      (24%), kidney (16%), and urinary tract (15%). The most commonly studied pathology
      was urinary calculi (28%), renal lesion/tumor (23%), and hepatic lesion/tumor
      (20%). Our study identifies intellectual milestones in the applications of DECT
      in abdominal radiology. The diversity of the articles reflects on the
      characteristics and quality of the most influential publications related to DECT.

PMID- 29657642
TI  - Quantitative Computed Tomography (CT) Assessment of Emphysema in Patients with
      Severe Chronic Obstructive Pulmonary Disease (COPD) and its Correlation with Age,
      Sex, Pulmonary Function Tests, BMI, Smoking, and Biomass Exposure.
AB  - Background: To evaluate the role of HRCT in quantifying emphysema in severe COPD
      patients and to study the variations in the pattern of emphysema in relation to
      age, sex, FEV1, smoking index, biomass exposure, and BMI. Material/Methods:
      Automatic lung segmentation of HRCT scans in 41 severe COPD patients (GOLD stage
      III or more) was done using an emphysema protocol. The extent of emphysema was
      assessed using the density mask method with a threshold of -950 HU (%LAA-950).
      The percentage of emphysema in each lung lobe and both lungs was correlated with
      6 parameters - age, sex, BMI, smoking index, biomass exposure, and FEV1. Results:
      Smoking resulted in homogenously distributed emphysema regardless of the severity
      of smoking. BMI was inversely correlated with the extent of emphysema. A
      significant association was found between the percentage of emphysema in the
      right lower lobe and BMI (P=0.015), between biomass exposure and the percentage
      of emphysema in RUL, RLL, and both lungs (P values of 0.024, 0.016, and 0.036,
      respectively). The extent of emphysema was disproportionately low compared to the
      amount of obstruction on PFTs, indicating an airway predominant variety of COPD
      with significant biomass exposure. Conclusions: Smoking is associated with a
      relatively homogenous distribution of emphysema with no regional predilection.
      Biomass exposure produces predominantly right-sided emphysema. BMI decreases with
      increasing levels of emphysema in the right lower lobe. These risk factors of
      emphysema patterns are helpful in deciding on the management, including surgical
      options.

PMID- 29657643
TI  - Evaluation of Pancreas with Strain Elastography in Children with Type 1 Diabetes
      Mellitus.
AB  - Background: To investigate changes in pancreatic elasticity in children with type
      1 diabetes mellitus (T1DM). Material/Methods: The study group consisted of 60
      children with T1DM, and the control group was comprised of 60 healthy children.
      Strain ratios were obtained for the pancreas using ultrasound strain elastography
      (Toshiba Applio 500 device). Baseline descriptive data, hemoglobin A1c (%) level,
      time since diagnosis of T1DM (months), and strain ratio values were noted and
      compared between the 2 groups. Furthermore, correlation between strain ratio
      values and other variables was investigated. Results: ROC analysis yielded an
      optimal cut-off value of 2.245 (AUC=0.999, p<0.001, sensitivity=0.983,
      specificity=1.00) for the strain ratio. Strain ratio values greater than 2.245
      were likely to be pathological, which could be attributed to increased tissue
      stiffness in T1DM. The strain ratio was significantly higher in T1DM patients
      than in the control group (3.38+/-0.66 vs. 1.32+/-0.35; p<0.001). The strain
      ratio correlated positively with age and duration of T1DM (p<0.001 for both), and
      there was a correlation between the strain ratio and age in the control group
      (p=0.011). Conclusions: Strain elastography is a promising, safe, non-invasive,
      and practical method for early detection, long-term screening, and follow-up in
      children with T1DM.

PMID- 29657644
TI  - Evaluation of Imaging Parameters of Ultrasound Scanners: Baseline for Future
      Testing.
AB  - Background: Regular quality control is required in Poland only for those methods
      of medical imaging which involve the use of ionizing radiation but not for
      ultrasonography. It is known that the quality of ultrasound images may be
      affected by the wearing down or malfunctioning of equipment. Material/Methods: An
      evaluation of image quality was carried out for 22 ultrasound scanners equipped
      with 46 transducers. The CIRS Phantom model 040GSE was used. A set of tests was
      established which could be carried out with the phantom, including: depth of
      penetration, dead zone, distance measurement accuracy, resolution, uniformity,
      and visibility of structures. Results: While the dead zone was 0 mm for 89% of
      transducers, it was 3 mm for the oldest transducer. The distances measured agreed
      with the actual distances by 1 mm or less in most cases, with the largest
      difference of 2.6 mm. The resolution in the axial direction for linear
      transducers did not exceed 1 mm, but it reached even 5 mm for some of the convex
      and sector transducers, especially at higher depths and in the lateral direction.
      For 29% of transducers, some distortions of anechoic structures were observed.
      Artifacts were detected for several transducers. Conclusions: The results will
      serve as a baseline for future testing. Several cases of suboptimal image quality
      were identified along with differences in performance between similar
      transducers. The results could be used to decide on the applicability of a given
      scanner or transducer for a particular kind of examination.

PMID- 29657645
TI  - Kaleidoscopic View of Bowel Tuberculosis on Multi- Detector Computed Tomography
      (CT) Enterography - A Novel Technique Unfolding an Archaic Disease.
AB  - Gastrointestinal tuberculosis (GI TB) is an important manifestation of abdominal
      tuberculosis (TB), an extra-pulmonary form of the disease. GI TB commonly affects
      the small bowel but is difficult to diagnose due to the challenge of evaluating
      the entire length of overlapping small bowel loops with traditional diagnostic
      methods like Barium meal follow through, abdominal computed tomography (CT), and
      endoscopy. New techniques of CT/MR enteroclysis/enterography are now available
      which specifically image the small bowel. MDCT enterography (MDCTE) is a non
      invasive, simple to perform, modified abdominal CT imaging technique permitting
      reasonably accurate evaluation of the small bowel lumen, wall, perienteric
      tissues, and solid organs within the abdomen. As GI TB can cause morphological
      alterations in and around the small bowel, MDCTE seems to be an attractive
      modality for patients suspected of abdominal or GI TB. As scarce literature is
      available on MDCTE on tuberculosis, we present a pictorial review on MDCTE
      findings in patients with GI tuberculosis proved on FNAC and clinical and/or
      imaging follow-up.

PMID- 29657646
TI  - Iterative Reconstruction as a Method for Optimisation of Computed Tomography
      Procedures.
AB  - Background: Computed tomography (CT) is still commonly regarded as a method that
      causes a high radiation exposure. For that reason, producers intensively try to
      find new solutions for dose reduction while maintaining a high diagnostic value
      of images. One of the recent strategies focuses on CT image reconstruction.
      Iterative reconstruction (IR) is an alternative for filtered back projection
      (FBP) that is commonly used today.The aim of the article is to demonstrate and
      compare the effects of two IR algorithms on dose value and image details.
      Material/Methods: Investigations were performed on two 128 multi-detector (MDCT)
      CT scanners: - iCT (Philips Healthcare with iDose4); - Definitions AS+ (Siemens
      Medical Solutions with SAFIRE system).The measurements involved: - image quality
      indicators for the CATPHAN 600 phantom; - dosimetric indicators of exposure (DLP
      i CTDIvol). Results: The signal-to-noise ratios (SNR) in the images reconstructed
      with IR and FBP were analysed, and the SNR(IR)/SNR(FBP) ratios were calculated
      and correlated with CTDIvol values. The effects of IR and FBP algorithms on low
      contrast resolution were also compared in relation to CTDIvol values. The
      smallest diameter of supra-slice objects in the Catphan phantom were taken into
      consideration.Both iterative algorithms definitely improved the visibility of low
      contrast objects in comparison to a standard algorithm (FBP) with similar
      exposure parameters.These algorithms allow an 80% reduction of the CTDIvol value
      while maintaining an acceptable visibility of low-contrast objects. However, the
      results obtained with each of the studied iterative algorithms differ.

PMID- 29657647
TI  - Echocardiography in the Evaluation of Chest Pain in the Emergency Department.
AB  - Background: A challenge for clinicians in emergency departments (EDs) is rapid
      identification of those patients with chest pain who require admission and urgent
      management and those with low clinical risk who can be discharged safely from the
      ED. This study was designed with an aim to evaluate the ability of two
      dimensional transthoracic echocardiography (2D-TTE) to determine causes of acute
      chest pain in patients presenting to the ED in order to decide whether hospital
      admission and further investigations were needed. Material/Methods: A total of
      250 consecutive patients admitted with chest pain, were enrolled in this
      prospective study. Patients were divided into three groups: high risk, moderate
      risk, and low risk of cardiac events, according to cardiovascular risk factors.
      2D-TTE was obtained using the HI vision Avius ultrasound unit (Hitachi).
      Statistical analysis was performed with the Statistical Package for the Social
      Sciences (SPSS), version 20. Results: Ischemic and/or non-ischemic heart diseases
      (IHD and/or NIHD) were detected in 147 (86.5%), 13 (7.6%), and 10 (5.9%) patients
      with high, moderate, and low risk, respectively. 2D-TTE was characterized by
      sensitivity of 85.86%, specificity of 100%, and positive predictive value (PPV)
      of 100% for detecting causes of chest pain. Conclusions: 2D-TTE increased
      specificity and sensitivity of detecting causes of chest pain, when compared to
      patient history, clinical findings, and electrocardiography (ECG). 2D-TTE can be
      used to help determine the need for hospital admission, to confirm or exclude
      diagnosis, and guide urgent therapy.

PMID- 29657648
TI  - Radiologist as a Leader in the Diagnostic Process in Patients with Prostate
      Cancer.
AB  - Multiparametric MRI of the prostate gland is a relatively new diagnostic modality
      which is gathering a growing interest among urologists and radiologists. The
      second version of the PI-RADS guidelines enabled standardized imaging, evaluation
      and reporting of prostatic lesions. Nonetheless, since 2015 - when the PI-RADS
      v.2 was published, numerous questions regarding imaging of the prostate gland
      have appeared.

PMID- 29657649
TI  - The Predictive Value of Multidetector High Resolution Computed Tomography in
      Evaluation of Suspected Sputum Smear Negative Active Pulmonary Tuberculosis in
      Egyptian Zagazig University Hospital Patients.
AB  - The aim of this work is to study the usage of multi-detector HRCT chest in
      diagnosing pulmonary TB cases whose sputum smears are negative and making a
      correlation between their CT features and their sputum culture results. This
      study was carried out from December 2014 to December 2016 at Zagazig university
      hospitals, Radiodiagnosis department. It included 150 patients. Their ages ranged
      between 10 to 70 years with a mean age 40 years. They were referred from the
      outpatient respiratory medicine clinic of the hospital. All patients had been
      presented clinically with suspicion of PTB. Their clinical features and HRCT
      findings were investigated to predict the risk for PTB. We then designed
      provisional HRCT diagnostic criteria based on the results to rank the risk of
      PTB. A positive tuberculin skin test alone among clinical laboratory findings was
      significantly associated with an increase of risk of PTB. Centrilobular nodules,
      large nodules, tree-in-bud appearance and the main lesion being located in S1,
      S2, and S6 lung segments were significantly associated with an increased risk of
      PTB. At HRCT 40 out of 44 patients with class III ranking showed active pulmonary
      TB. 12 out of 51 patients presented with class II ranking and 8 out of 40 were
      ranked as class I. The sensitivity, specificity and positive likelihood ratio of
      class I ranking HRCT criteria to diagnose active pulmonary TB were 95%, 40% and
      1.4, respectively. Class II ranking results were 85%, 72%, 3, respectively.
      Finally class III ranking results were 45%, 90%, 11.5, respectively. Cases
      suspected of having active pulmonary TB whose smears are negative can benefit
      from MD HRCT chest findings to predict those patients of high risk with good
      reproducibility.

PMID- 29657650
TI  - Evaluation of Alterations in Tumor Tissue of Gastrointestinal Stromal Tumor
      (GIST) in Computed Tomography Following Treatment with Imatinib.
AB  - Background: The aim of this study was to evaluate the alterations in the
      neoplastic tissue of GIST following Imatinib treatment. Material/Methods: CT
      studies of 14 patients with inoperable primary tumors and 56 patients with
      metastatic and recurrent disease after chemotherapy were analyzed
      retrospectively. The following alterations in features of primary and secondary
      tumors were analyzed: dimension, degree and type of contrast enhancement,
      outlines of lesions, presence of intratumoral bleeding, presence of
      calcifications. Results: In the analyzed group of primary, metastatic and
      recurrent tumors after treatment with Imatinib in most cases a decrease in size
      and contrast enhancement were observed; the outlines of lesions became well
      circumscribed. Following the treatment, the number of tumors enhancing
      inhomogeneously decreased. In primary tumors the percentage of calcifications
      increased, whereas in metastatic tumors calcifications were observed only after
      treatment. There was no bleeding found within primary tumors after treatment. In
      metastatic disease, increased percentage of tumors with transient intratumoral
      bleeding was observed. There were also some unconventional CT images following
      treatment, such as: cystic transformation of lesions, enlargement of lesions,
      appearing of new lesions suggesting progression of the disease, stationary
      dimensions of lesions during local progression of the disease, simultaneous
      decrease and increase in size of metastatic lesions or appearance of new ones.
      Conclusions: Right from the start of Imatinib therapy in inoperable and
      disseminated GIST patients, specific CT images, not seen during conventional
      cytotoxic chemotherapy, were observed.

PMID- 29657651
TI  - Role of Magnetic Resonance Imaging, Magnetic Resonance Spectroscopy and
      Transrectal Ultrasound in Evaluation of Prostatic Pathologies with Focus on
      Prostate Cancer.
AB  - Background: Prostate cancer (PC) is an important medical and socio-economical
      problem due to its increasing incidence. The development of the prostate specific
      antigen (PSA) test, and a continuing decrease in the rates of other common
      neoplasms, such as lung and stomach since mid-1980s, prostate cancer has become
      one of the most common cancers among men. Prostate cancer (PC) is the second most
      common cancer in men, preceded only by lung cancer, and its early diagnosis is
      crucial for a successful treatment, that will prolong survival and improve
      quality of life.The main objective of our study was to evaluate the role of
      magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS) and
      transrectal ultrasound (TRUS) in detecting prostatic pathologies and staging of
      prostate cancer by correlating these methods with histopathological results.
      Material/Methods: The study is a cross-sectional diagnostic study performed in 66
      patients with a high degree of clinical suspicion of prostatic pathology. All
      patients underwent TRUS, T1W, T2W, DWI, and 3D PRESSMRS sequences, and we also
      calculated ADC values and Cho Cr/Cit MRS ratios for all patients. Results:
      Combination of MRI and MRS showed the highest diagnostic accuracy among the
      imaging modalities in detecting of prostatic neoplasm, followed by MRI, and then
      by TRUS. MRS plays a complementary role to MRI, by increasing its diagnostic
      accuracy. Due to a high cost, limited availability and increased scanning time,
      combination of MRI and MRS is currently not recommended as a first line
      investigation for detecting prostate neoplasms, hence USG (TRUS) remains the
      first line investigation due to its low cost, easy availability, time
      effectiveness and comparable efficacy. Conclusions: MRI MRS has more diagnostic
      accuracy than MRI alone for detection of prostate pathologies. MRS, plays
      significant complementary role and should be included in the routine MR imaging
      protocols. MRI helps in diagnosis, localization, better tissue characterization
      and staging of prostate cancer. TRUS is easily available, cost effective and has
      comparable efficacy.

PMID- 29657652
TI  - Multiple Brain Abscesses Caused by Citrobacter Koseri in a Preterm Neonate - Case
      Report.
AB  - Background: Brain abscesses are very rarely diagnosed in neonates, but if
      present, they are associated with a high risk of severe complications and
      mortality. In neonates, brain abscesses can be detected on transfontanelle
      ultrasonography, in which they appear as hyperechogenic lesions surrounded by a
      hypoechogenic border. Case Report: We present a female neonate, born in the 28th
      week of gestation, with birth weight of 950 grams, who was born in an ambulance
      by spontaneous vaginal vertex delivery. No signs of infection were present until
      the 35th day of hospitalization, when a sudden and serious deterioration in the
      patient's condition was observed due to late-onset sepsis. Cranial US, performed
      on the 40th day of life, revealed hyperechogenic lesions with a hypoechogenic
      halo in the right frontal lobe, which could correspond to brain abscesses. These
      lesions were caused by Citrobacter koseri septicaemia, identified by
      transfontanelle ultrasonography, and confirmed on magnetic resonance imaging. The
      patient recovered and was discharged on the 91th day of life (39 PCA) with a
      recommendation of permanent neurological surveillance. Conclusions:
      Ultrasonography of the central nervous system can reveal inflammatory changes and
      developing brain abscesses. In neonates, magnetic resonance imaging should be
      performed as the method of choice for confirming brain abscesses.

PMID- 29657653
TI  - Diagnostic Imaging and Clinical Features of Intracranial Hypotension - Review of
      Literature.
AB  - Intracranial hypotension (IH) is an uncommon, benign, and usually self-limiting
      condition caused by low cerebrospinal fluid (CSF) pressure, usually due to CSF
      leakage. The dominant clinical finding is an orthostatic headache. Other common
      clinical features include fever, nausea, vomiting, and tinnitus. Magnetic
      resonance imaging (MRI) plays an important role in the diagnosis and follow-up of
      patients with IH. Specific MRI findings include intracranial pachymeningeal
      enhancement, sagging of the brain, pituitary enlargement, and subdural fluid
      collections. Intracranial hypotension can mimic other conditions such as aseptic
      meningitis or pituitary adenomas. Differential diagnosis is important, because
      misdiagnosis may lead to unnecessary procedures and prolonged morbidity.

PMID- 29657654
TI  - A particle manipulation method and its experimental study based on opposed jets.
AB  - A particle manipulation method was presented in this paper based on opposed jets.
      In such a method, particles were trapped near the stagnation point of the flow
      field and moved by controlling the position of the stagnation point. The hold
      direction of the flow to the particle was changed by changing the orientation of
      the opposed-jet flow field where a particle is trapped. Subsequently, the
      directional and quantitative movement of the particle in any direction was
      achieved. Taking micron particles as examples, we analyzed the control mechanism
      of particles based on opposed jets and evaluated the influence of jet velocity,
      inner diameter, distance of end face, radial error, and position of capillaries
      on the particle control performance by simulations. The feasibility of the
      proposed method was proved by a great number of experiments, and the results
      demonstrated that particles with the arbitrary size and shape can be trapped and
      moved directionally and quantitatively by constructing an opposed-jet flow field.
      The trapping and position control of particles can be manipulated without any
      contact with proper flow field parameters.

PMID- 29657655
TI  - Detection of viability of micro-algae cells by optofluidic hologram pattern.
AB  - A rapid detection of micro-algae activity is critical for analysis of ship
      ballast water. A new method for detecting micro-algae activity based on lens-free
      optofluidic holographic imaging is presented in this paper. A compact lens-free
      optofluidic holographic imaging device was developed. This device is mainly
      composed of a light source, a small through-hole, a light propagation module, a
      microfluidic chip, and an image acquisition and processing module. The excited
      light from the light source passes through a small hole to reach the surface of
      the micro-algae cells in the microfluidic chip, and a holographic image is formed
      by the diffraction light of surface of micro-algae cells. The relation between
      the characteristics in the hologram pattern and the activity of micro-algae cells
      was investigated by using this device. The characteristics of the hologram
      pattern were extracted to represent the activity of micro-algae cells. To
      demonstrate the accuracy of the presented method and device, four species of
      micro-algae cells were employed as the test samples and the comparison
      experiments between the alive and dead cells of four species of micro-algae were
      conducted. The results show that the developed method and device can determine
      live/dead microalgae cells accurately.

PMID- 29657656
TI  - Chemotactic behavior of spermatozoa captured using a microfluidic chip.
AB  - Chemotaxis, as a mechanism for sperm guidance in vivo, is an enigma which has
      been difficult to demonstrate. To address this issue, various devices have been
      designed to study sperm chemotaxis in vitro. Limitations of traditional
      chemotaxis devices were related to the inability to maintain a stable
      concentration gradient as well as track single sperm over long times.
      Microfluidics technology, which provides superior control over fluid flow, has
      been recently used to generate stable concentration gradients for investigating
      the chemotactic behavior of several cell types including spermatozoa. However,
      the chemotactic behavior of sperm has not been unequivocally demonstrated even in
      these studies due to the inability to distinguish it from rheotaxis, thermotaxis,
      and chemokinesis. For instance, the presence of fluid flow in the microchannels
      not only destabilizes the concentration gradient but also elicits a rheotactic
      response from sperm. In this work, we have designed a microfluidic device which
      can be used to establish both, a uniform concentration and a uniform
      concentration gradient in a stationary fluid. By facilitating measurement of
      sperm response in ascending, descending ,and uniform chemoattractant
      concentration, the assay could isolate sperm chemotactic response from rheotaxis
      and chemokinesis. The device was validated using acetylcholine, a known
      chemoattractant and further tested with rat oviductal fluid from the estrus
      phase.

PMID- 29657657
TI  - Engineering small tubes with changes in diameter for the study of kidney cell
      organization.
AB  - Multicellular tubes are structures ubiquitously found during development and in
      adult organisms. Their topologies (diameter, direction or branching), together
      with their mechanical characteristics, play fundamental roles in organ function
      and in the emergence of pathologies. In tubes of micrometric range diameters,
      typically found in the vascular system, renal tubules or excretory ducts, cells
      are submitted to a strong curvature and confinement effects in addition to flow.
      Then, small tubes with change in diameter are submitted to a local gradient of
      shear stress and curvature, which may lead to complex mechanotransduction
      responses along tubes, and may be involved in the onset or propagation of cystic
      or obstructive pathologies. We describe here a simple method to build a
      microfluidic device that integrates cylindrical channels with changes in diameter
      that mimic in vivo tube geometries. This microfabrication approach is based on
      molding of etched tungsten wires, which can achieve on a flexible way any change
      in diameter in a polydimethylsiloxane (PDMS) microdevice. The interest of this
      biomimetic multitube system has been evidenced by reproducing renal tubules on
      chip. In particular, renal cell lines were successfully seeded and grown in PDMS
      circular tubes with a transition between 80 MUm and 50 MUm diameters. Thanks to
      this biomimetic platform, the effect of the tube curvature has been investigated
      especially regarding cell morphology and orientation. The effect of shear stress
      on confluent cells has also been assessed simultaneously in both parts of tubes.
      It is thus possible to study interconnected cell response to differential
      constraints which is of central importance when mimicking tubes present in the
      organism.

PMID- 29657658
TI  - 3D-glass molds for facile production of complex droplet microfluidic chips.
AB  - In order to leverage the immense potential of droplet microfluidics, it is
      necessary to simplify the process of chip design and fabrication. While
      polydimethylsiloxane (PDMS) replica molding has greatly revolutionized the chip
      production process, its dependence on 2D-limited photolithography has restricted
      the design possibilities, as well as further dissemination of microfluidics to
      non-specialized labs. To break free from these restrictions while keeping
      fabrication straighforward, we introduce an approach to produce complex multi
      height (3D) droplet microfluidic glass molds and subsequent chip production by
      PDMS replica molding. The glass molds are fabricated with sub-micrometric
      resolution using femtosecond laser machining technology, which allows directly
      realizing designs with multiple levels or even continuously changing heights. The
      presented technique significantly expands the experimental capabilities of the
      droplet microfluidic chip. It allows direct fabrication of multilevel structures
      such as droplet traps for prolonged observation and optical fiber integration for
      fluorescence detection. Furthermore, the fabrication of novel structures based on
      sloped channels (ramps) enables improved droplet reinjection and picoinjection or
      even a multi-parallelized drop generator based on gradients of confinement. The
      fabrication of these and other 3D-features is currently only available at such
      resolution by the presented strategy. Together with the simplicity of PDMS
      replica molding, this provides an accessible solution for both specialized and
      non-specialized labs to customize microfluidic experimentation and expand their
      possibilities.

PMID- 29657659
TI  - NONSEPARABLE DYNAMIC NEAREST NEIGHBOR GAUSSIAN PROCESS MODELS FOR LARGE SPATIO
      TEMPORAL DATA WITH AN APPLICATION TO PARTICULATE MATTER ANALYSIS.
AB  - Particulate matter (PM) is a class of malicious environmental pollutants known to
      be detrimental to human health. Regulatory efforts aimed at curbing PM levels in
      different countries often require high resolution space-time maps that can
      identify red-flag regions exceeding statutory concentration limits. Continuous
      spatio-temporal Gaussian Process (GP) models can deliver maps depicting predicted
      PM levels and quantify predictive uncertainty. However, GP-based approaches are
      usually thwarted by computational challenges posed by large datasets. We
      construct a novel class of scalable Dynamic Nearest Neighbor Gaussian Process
      (DNNGP) models that can provide a sparse approximation to any spatio-temporal GP
      (e.g., with nonseparable covariance structures). The DNNGP we develop here can be
      used as a sparsity-inducing prior for spatio-temporal random effects in any
      Bayesian hierarchical model to deliver full posterior inference. Storage and
      memory requirements for a DNNGP model are linear in the size of the dataset,
      thereby delivering massive scalability without sacrificing inferential richness.
      Extensive numerical studies reveal that the DNNGP provides substantially superior
      approximations to the underlying process than low-rank approximations. Finally,
      we use the DNNGP to analyze a massive air quality dataset to substantially
      improve predictions of PM levels across Europe in conjunction with the LOTOS
      EUROS chemistry transport models (CTMs).

PMID- 29657660
TI  - Mechanism Associated with Kaolinite Intercalation with Urea: Combination of
      Infrared Spectroscopy and Molecular Dynamics Simulation Studies.
AB  - Intercalation of urea in kaolinite was investigated using infrared spectroscopy
      and molecular dynamics simulation. Infrared spectroscopic results indicated the
      formation of hydrogen bonds between urea and siloxane/alumina surfaces of
      kaolinite. The carbonyl group (-C=O) of urea acted as H-acceptors for the
      hydroxyl groups on alumina surfaces. The amine group (-NH2) of urea functioned as
      H-donors interacting with basal oxygens on siloxane surfaces and/or the oxygens
      of hydroxyl groups on alumina surfaces. The H-bonds of urea formed with kaolinite
      surfaces calculated directly from molecular dynamics simulation was consistent
      with the infrared spectroscopic results. Additionally, MD simulations further
      provided insight into the interaction energies of urea with the kaolinite
      interlayer environment. The calculated interaction energies of urea molecules
      with kaolinite alumina and siloxane surfaces suggest that the intercalation of
      urea within kaolinite interlayers is energetically favorable. The interaction
      energy of urea with alumina surfaces was greater than that with siloxane
      surfaces, indicating that the alumina surface plays a primary role in the
      intercalation of kaolinite by urea. The siloxane surfaces function as H-acceptors
      to facilitate the intercalation of urea. The present study offers a direct view
      of the specific driving force involved in urea intercalation in kaolinite. The
      results obtained can help develop appropriate protocol to intercalate and
      delaminate clay layers for clay-based applications and products.

PMID- 29657661
TI  - Thermodynamic Mechanism and Interfacial Structure of Kaolinite Intercalation and
      Surface Modification by Alkane Surfactants with Neutral and Ionic Head Groups.
AB  - Intercalation and surface modification of clays with surfactants are the
      essential process to tailor the clays' surface chemistry for their extended
      applications. A full understanding of the interaction mechanism of surfactants
      with clay surfaces is crucial to engineer clay surfaces for meeting a particular
      requirement of industrial applications. In this study, the thermodynamic
      mechanism involved in the intercalation and surface modification of methanol
      preintercalated kaolinite by three representative alkane surfactants with
      different head groups, dodecylamine, cetyltrimethylammonium chloride (CTAC), and
      sodium stearate, were investigated using the adaptive biasing force accelerated
      molecular dynamics simulations. In addition, the interaction energies of
      surfactants with an interlayer environment (alumina surface, siloxane surface,
      and interlayer methanol) of methanol preintercalated kaolinite were also
      calculated. It was found that the intercalation free energy of CTAC with a
      cationic head group was relatively larger than that of stearate with an anionic
      head group and dodecylamine with a neutral head group. The attractive
      electrostatic and van der Waals interactions of surfactants with an interlayer
      environment contributed to the intercalation and surface modification process
      with the electrostatic force playing the significant role. This study revealed
      the underlying mechanism involved in the intercalation and surface modification
      process of methanol preintercalated kaolinite by surfactants, which can help in
      further design of kaolinite-based organic clays with desired properties for
      specific applications.

PMID- 29657662
TI  - Molecular Dynamics Simulation of Basal Spacing, Energetics, and Structure
      Evolution of a Kaolinite-Formamide Intercalation Complex and Their Interfacial
      Interaction.
AB  - Molecular dynamics simulations were performed on kaolinite-formamide complex
      models with various numbers of formamide molecules loaded in the kaolinite
      interlayer to explore the basal spacing, energetics, and structure evolution of
      the kaolinite-formamide complex during the intercalation process. Additionally,
      the interfacial interactions of formamide with kaolinite interlayer surfaces were
      calculated. The calculation revealed that the basal spacing of kaolinite was
      enlarged to 9.6 A at the beginning of intercalation. Formamide was arranged as a
      monolayer structure in the kaolinite interlayer with the molecular plane oriented
      at small angles with respect to the interlayer surface. With continuous
      intercalation, the basal spacing readily reached a stable stage at 10.6 A, where
      formamide rearranged its structure by rotating the molecule plane along the C-N
      bond that was parallel to the interlayer surface, which resulted in the molecular
      plane orienting at higher angles with respect to the interlayer surface. During
      this process, the C?O groups oriented toward the hydroxyl groups on the
      interlayer octahedral surface, and one of N-H bonds progressively pointed toward
      the basal oxygens on the opposing interlayer tetrahedral surface. Continuous
      intercalation can enlarge the basal spacing to more than 14 A with the
      prerequisite of overcoming the energy barrier, and then formamide evolved to a
      disordered bilayer structure in the kaolinite interlayer. The affinity of
      kaolinite interlayer surfaces for formamide motivated the intercalation process.
      The octahedral surface displayed a relatively larger affinity toward formamide
      compared to the tetrahedral surface partially due to the presence of hydroxyl
      groups that are more active in the intermolecular interactions with formamide.

PMID- 29657663
TI  - Clean Heat: A Technical Response to a Policy Innovation.
AB  - New York City clean heat policies were enacted to improve air quality, especially
      reducing exposure to black carbon, particulate matter and sulfur that are linked
      to environmental degradation and various health risks. This policy measure
      specifically called for the phase out of residual oil and adoption of cleaner
      burning fuel sources through boiler conversions in commercial and residential
      properties throughout the city. This paper describes the process of clean heat
      technology adoption within the innovative clean heat policy context demonstrating
      its thorough compliance and discussing implications for scalability in other
      urban settings.

PMID- 29657664
TI  - Salvage of Free Flaps Following Vascular Pedicle Avulsion Using
      "Supermicrosurgery" Techniques: A Case Report of DIEP Free Flap Salvage and
      Review of the Literature.

PMID- 29657665
TI  - Environmental determinants of previtamin D synthesis in the United Arab Emirates.
AB  - Despite abundant sunshine throughout the year, vitamin D deficiency is endemic in
      the UAE. Solar radiation within the UVB range of the spectrum is required for the
      photosynthesis of previtamin D3 in the skin. Atmospheric transmission of UVB is
      strongly influenced by atmospheric conditions and solar zenith angle. We
      investigated the effects of diurnal and seasonal variation on the availability of
      sufficient UVB radiation for adequate previtamin D3 synthesis using an
      established in vitro model. Borosilicate ampoules of 7-dehydrocholesterol, the
      precursor of previtamin D3, in ethanol (50 ug/mL) were exposed to direct sunlight
      in an urban area of Abu Dhabi, at one hourly intervals between 0800 and 1700, on
      one day of each month over a period of one year. Conversion to previtamin D3,
      vitamin D3 and metabolically inactive photoisomers was analyzed using high
      performance liquid chromatography. The efficiency of 7-dehydrocholesterol
      conversion to previtamin D3 varied estimated UVB intensity. At the latitude of
      Abu Dhabi (24.2 N) previtamin D3 synthesis can occur throughout the year. However
      very little if any previtamin D3 was produced before 0900 hrs.and after 1600 hrs.
      Local conditions in Abu Dhabi are likely sufficient to maintain vitamin D levels
      throughout the year given adequate sun exposure.

PMID- 29657666
TI  - On nearest-neighbor Gaussian process models for massive spatial data.
AB  - Gaussian Process (GP) models provide a very flexible nonparametric approach to
      modeling location-and-time indexed datasets. However, the storage and
      computational requirements for GP models are infeasible for large spatial
      datasets. Nearest Neighbor Gaussian Processes (Datta A, Banerjee S, Finley AO,
      Gelfand AE. Hierarchical nearest-neighbor gaussian process models for large
      geostatistical datasets. J Am Stat Assoc 2016., JASA) provide a scalable
      alternative by using local information from few nearest neighbors. Scalability is
      achieved by using the neighbor sets in a conditional specification of the model.
      We show how this is equivalent to sparse modeling of Cholesky factors of large
      covariance matrices. We also discuss a general approach to construct scalable
      Gaussian Processes using sparse local kriging. We present a multivariate data
      analysis which demonstrates how the nearest neighbor approach yields inference
      indistinguishable from the full rank GP despite being several times faster.
      Finally, we also propose a variant of the NNGP model for automating the selection
      of the neighbor set size.

PMID- 29657667
TI  - Efficacy, Safety, and Potency of Betamethasone Dipropionate Spray 0.05%: A
      Treatment for Adults with Mild-to-moderate Plaque Psoriasis.
AB  - Objective: A spray formulation of betamethasone dipropionate 0.05% (BD spray
      0.05%; SernivoTM [betamethasone dipropionate] Spray 0.05%; Promius Pharma, LLC;
      Princeton, New Jersey, USA) has been developed for the topical treatment of
      psoriasis. The objective of these studies was to evaluate the efficacy, safety,
      and potency of BD spray 0.05%. Design, Setting, Participants, and Measurements:
      Efficacy and safety were assessed in a randomized, vehicle-controlled, double
      blind study in adults with moderate plaque psoriasis (ClinicalTrials.gov
      identifier: NCT01947491). Additionally, the potential for adrenal suppression and
      systemic absorption was evaluated in a randomized, open-label study in healthy
      adults (ClinicalTrials.gov identifier: NCT02070965). Potency was measured in two
      single-point, randomized, evaluator-blinded studies in healthy adults. Results:
      BD spray 0.05% was significantly more effective than the vehicle spray in
      subjects with moderate plaque psoriasis after three, 14, and 28 days of twice
      daily treatment. The efficacy of BD spray 0.05% was similar to augmented BD
      lotion 0.05% after 14 days of treatment. The safety of BD spray 0.05% was similar
      to that of the vehicle spray over 28 days and to that of augmented BD lotion
      0.05% over 14 days. Under maximal use conditions for up to 29 days, the potential
      for adrenal suppression was no greater with BD spray 0.05% than with a 15-day
      regimen of augmented BD lotion 0.05%. There was less systemic absorption of BD
      from BD spray 0.05% than from augmented BD lotion 0.05%. Studies classify BD
      spray 0.05% as a midpotent corticosteroid. Conclusions: BD spray 0.05%, a
      midpotent corticosteroid, is an effective and well-tolerated treatment for adults
      with mild to moderate plaque psoriasis.

PMID- 29657668
TI  - Association of Cutaneous Amyloidosis with Neurodegenerative Amyloidosis:
      Correlation or Coincidence?
AB  - Neurodegenerative disorders such as Alzheimer's disease and localized cutaneous
      macular amyloidosis are conditions that result from protein misfolding. These
      disorders share common pathogenic mechanisms that lead to the deposition of
      amyloid protein. Currently, there is a paucity of data on the connection between
      the brain and skin amyloidosis. Few recent studies have demonstrated a strong
      connection between the brain and skin in different amyloid diseases. Here, we
      report a case of concurrent occurrence of skin and brain amyloidoses and explore
      the brain-skin axis connection.

PMID- 29657669
TI  - Dual Effect of Photobiomodulation on Melasma: Downregulation of Hyperpigmentation
      and Enhanced Solar Resistance-A Pilot Study.
AB  - Overview. Melasma is a resistant, sun-induced facial hyperpigmentation capable of
      remaining present for decades with ensuing psychological distress. Treatment is
      difficult and focuses on an array of measures to reduce skin hyperpigmentation
      resulting from triggered hyperactive melanocytes. The pathogenesis of melanoma is
      not clearly understood but it has been reported that some growth factors and
      specific cell-signaling pathways are involved. Objective. The objective of the
      current study was to evaluate the use of pulsed photobiomodulation to modulate
      melasma via the regulation of gene expression pertaining to skin pigmentation.
      Methods. We evaluated a two-step approach via a spilt-face pilot study involving
      seven patients with bilateral dermal melasma who had formerly undergone
      unsuccessful treatments. During treatment, the initial mobilization phase with
      microdermabrasion was closely followed by the modulation phase, delivering low
      energy pulsed photons (940nm) to downregulate highly metabolic melanocytes in the
      dermis. A weekly treatment was performed for eight consecutive weeks. White light
      pictures, ultraviolet pictures, melanin index scores, and Melasma Area and
      Severity Index scores were obtained at baseline and at Week 12. Results. The
      pulsed photobiomodulation-treated side versus the control side showed
      statistically significant results for pigment reduction. Conclusion. This pilot
      study shows that dermal melasma can be significantly improved with pulsed
      photobiomodulation. Interestingly, it might also precondition the skin, helping
      it to build a resistance to future solar ultraviolet ray exposure.

PMID- 29657670
TI  - Evaluation and Proportion in Nasal Filling with Hyaluronic Acid.
AB  - The nose is an essential feature when considering the aesthetic appeal of the
      face. As aesthetic preferences vary from person to person, the concept of the
      "ideal" nose must be applied on a case-by-case basis, with respect to the
      classical patterns of anthropometry, sex, ethnic group, and psychosocial factors.
      Interest in less invasive procedures for nasal correction has increased
      considerably, among which is the emerging use of hyaluronic acid for nonsurgical
      rhinoplasty. In this article, the authors present an objective review of the
      anatomy of the nasal region, the evaluation and indications of nasal filling with
      hyaluronic acid, a description of the technique, and brief discussion of
      associated complications.

PMID- 29657671
TI  - Dermoscopy in the Diagnosis of Inflammatory Dermatoses: Systematic Review
      Findings Reported for Psoriasis, Lupus, and Lichen Planus.
AB  - Background: Dermoscopy is well established as a tool to improve the detection of
      cancerous skin growths. Published data suggest that dermoscopy might be useful in
      evaluating inflammatory dermatoses and in distinguishing between rashes and skin
      cancer. Objective: The authors sought to review the published literature
      regarding use of dermoscopy in the evaluation of inflammatory skin conditions.
      Methods: Using a systematic approach, the authors performed a literature search
      using the names of 146 inflammatory dermatoses and pairing each one separately
      with the search terms dermoscopy, dermatoscopy, and epiluminescence
      microscopy.Results: After eliminating those papers that did not meet inclusion
      requirements, the authors identified 201 studies for their review, with the
      majority consisting of case reports. The most commonly studied inflammatory
      conditions were psoriasis, lupus, and lichen planus. There was congruence among
      the studies identified in terms of the most common dermoscopic findings for each
      of these diseases. Conclusions: The use of dermoscopy in the evaluation of
      inflammatory dermatoses is a promising option. However, more rigorous studies are
      needed to determine the sensitivity and specificity of the dermoscopic findings
      for many inflammatory skin conditions.

PMID- 29657673
TI  - Use of Botulinum Toxin for the Correction of Mild Ptosis.
AB  - Background: Lid margin asymmetry and its associated compensatory mechanisms might
      cause patients to seek treatment to improve aesthetics. Surgery might not be
      indicated and can potentially worsen the asymmetry in these cases. Methods: A
      case series of three patients was organized to illustrate the use of botulinum
      toxin administered to the pre-tarsal orbicularis for the correction of micro
      ptosis and improved symmetry. The marginal reflex distance and tarsal platform
      show were measured on both sides. Measurements were made using ImageJ software on
      standardized frontal photographs taken pre- and post-injection. Results: The
      average increase in the marginal reflex distance was 0.914mm, with an average pre
      tarsal botulinum toxin dose of three units. The average change in tarsal platform
      show between the two eyes was 0.89mm. Conclusion: Botulinum toxin application to
      the pre-tarsal orbicularis oculi muscle might be a suitable option for the
      management of small eyelid margin asymmetries.

PMID- 29657672
TI  - Efficacy and Safety Evaluation of High-density Intense Pulsed Light in the
      Treatment of Grades II and IV Acne Vulgaris as Monotherapy in Dark-skinned Women
      of Child Bearing Age.
AB  - Background: Acne vulgaris is a self-limiting, chronic inflammatory disorder of
      the pilosebaceous unit characterized by exacerbations and remissions. It is often
      the early manifestation of puberty, and in girls it appears relatively early. In
      women, acne tends to become aggravated during the menstrual period, pregnancy,
      and in those who are on progesterone. Acne treatment is divided into two parts:
      topical and systemic. For Grades 1 and 2 acne, topical treatment is sufficient,
      while for Grades 3 and 4 acne, systemic drugs such as tetracyclines and retinoids
      are required to control the symptoms. Chemical peeling with glycolic and
      salicylic acids, cryosurgery with liquid nitrogen or carbon dioxide, and
      narrowband ultraviolet light are a few of the supportive procedural treatments
      available for Grades 3 and 4 acne. Objective: The author sought to determine the
      efficacy and safety of intense pulsed light (IPL) therapy (Magma-F-SR; FormaTK
      Systems, Tirat Carmel, Israel) in the treatment of Grades 3 and 4 acne as
      monotherapy in women of child-bearing age. Materials and Methods: One-hundred
      female patients with Grades 3 and 4 acne were enrolled in this study. All
      patients were treated with IPL using a 530nm to 1,200nm filter once a week for a
      total duration of six weeks. Patient and physician scores were assessed at Weeks
      1 and 6 after the last treatment. Clinical photographs were also reviewed to
      determine the degree of efficacy. Adverse effects were noted. Results: Eighty
      percent of the patients involved in this study reported a significant reduction
      in lesion count compared to baseline. The adverse events were minimal-to-mild
      erythema. Conclusion: IPL therapy with 530nm to 1,200nm filter is an effective
      and safe modality of treatment as monotherapy in managing inflammatory Grades 3
      and 4 of acne vulgaris in women of child-bearing age.

PMID- 29657675
TI  - This month's guideline: ACE emergency kit v1.2.

PMID- 29657674
TI  - United States Preventive Services Task Force Overstates Cosmetic Harms of Skin
      Cancer Screening.
AB  - The United States Preventive Services Task Force (USPSTF) 2016 recommendation for
      skin cancer screening in asymptomatic healthy adults concluded that current
      evidence is "insufficient to assess the balance and harms of visual skin
      examination." One contributing factor leading to the insufficient grade was a
      concern for cosmetic harms resulting from unnecessary biopsies or excisions. This
      commentary briefly highlights the pertinent studies and currently accepted
      methods for pigmented lesion biopsy. Reviewing these data will permit clinicians
      to more thoroughly analyze the USPSTF statement and might assist in routine
      assessment and management of suspicious pigmented lesions in adult patients.

PMID- 29657676
TI  - The Forgotten Role of Bystander CPR to Improve Out of Hospital Cardiac Arrest
      Outcomes in Oman.

PMID- 29657677
TI  - Immunoglobulin G4-Related Disease: An Update.
AB  - Immunoglobulin G4-related disease (IgG4-RD) is an increasingly recognized immune
      mediated condition comprised of a collection of disorders that share specific
      pathological, serological, and clinical features. IgG4-RD is a fibroinflammatory
      condition with a tendency to form tumors with inflammatory infiltrate with IgG4
      rich plasma cells and elevation of serum IgG4, which may affect virtually every
      organ and tissue. IgG4-related ophthalmic disease may present as dacryoadenitis,
      myositis, or involvement of other orbital tissue. Hypophysitis or pachymeningitis
      may manifest as cranial neuropathies. The diagnosis of IgG4-RD is based on a
      typical clinical scenario, supportive laboratory test, expected radiological
      characteristics, and distinct histopathological and immunohistochemical features.
      Corticosteroids and immunosuppressives form the mainline treatment.

PMID- 29657678
TI  - Safety of Sodium-Glucose Cotransporter 2 Inhibitors (SGLT2-I) During the Month of
      Ramadan in Muslim Patients with Type 2 Diabetes.
AB  - Objectives: Sodium-glucose cotransporter 2 inhibitors (SGLT2-I) are a new class
      of antidiabetic drugs that might increase the risk of dehydration and
      hypoglycemia, particularly during the month of Ramadan in which Muslims abstain
      from eating and drinking for 14-16 hours daily. We aimed to provide real-life
      evidence about the safety of SGLT2-I during Ramadan. Methods: All patients over
      the age of 18 years on SGLT2-I before Ramadan 2016 who would be fasting during
      Ramadan were included. Demographic data, detailed medical history including
      comorbidities and medication profile, and laboratory results were collected
      before and after Ramadan. We also conducted a phone interview to evaluate the
      frequency and severity of hypoglycemia and dehydration. Results: Of the total of
      417 patients, 113 (27.0%) experienced hypoglycemic events, and 93 of these
      (82.3%) checked their blood glucose using a glucometer. Confirmed hypoglycemia (<
      70 mg/dL) was observed in 78 (83.8%). The hypoglycemic events were significantly
      more frequent in the SGLT2-I plus insulin-treated group than in those treated
      with SGLT2-I plus oral hypoglycemic agents group (p < 0.001). Confirmed
      hypoglycemic events were more frequent in those using SGLT2-I plus intensive
      insulin compared to those using SGLT2-I plus basal insulin (p = 0.020). Symptoms
      of dehydration were seen in 9.3% (n = 39) of the total population. We observed
      statistically significant reductions in glycated hemoglobin and weight by the end
      of Ramadan (p < 0.001). There were no significant changes in lipid profile and
      creatinine levels by the end of the study. Conclusions: The use of insulin in
      combination with SGLT2-I increases the risk of hypoglycemia during Ramadan.
      Hypoglycemic events were mild and did not require hospital admission. However,
      careful monitoring during prolonged fasting is warranted. No significant harmful
      effects on renal function result from treatment with SGLT2-I during Ramadan.

PMID- 29657679
TI  - Induction of Apoptosis and Inhibition of Invasion in Gastric Cancer Cells by
      Titanium Dioxide Nanoparticles.
AB  - Objectives: Nanoparticles induce oxidative stress in cells and damage them
      through the cell membrane and DNA damage, eventually resulting in cell death.
      This study aimed to evaluate the effect of titanium dioxide (TiO2) nanoparticles
      on apoptosis induction and invasion of gastric cancer cell line, MKN-45. Methods:
      We used the MTT assay to assess proliferation of MKN-45 gastric cancer cells
      after exposure to different forms of TiO2 nanoparticles including amorph,
      brookite, anatase, and rutile coated with polyethylene glycol (PEG) and bovine
      serum albumin (BSA). Ethidium bromide and acridine orange staining were used to
      visualize cancer cell apoptosis, and the wound healing assay technique (migration
      test) was used to assay cancer cell invasion. Results: Viability and
      proliferation of cancer cells in the presence of various forms of TiO2
      nanoparticles were reduced (p <= 0.050). This reduction in cell proliferation and
      viability was directly related to concentration and duration of exposure to
      nanoparticles. Induction of cell death was seen in all groups (p <= 0.050).
      Increased cell invasion was seen in PEG-amorph TiO2 group compared to the control
      group. Cell invasion was decreased only in the brookite BSA group (p <= 0.050).
      Conclusions: Various forms of TiO2 nanoparticles reduced cell proliferation and
      induced apoptosis in cancer cells. Some forms of TiO2 nanoparticles such as
      brookite BSA also inhibited cell invasion. PEG-amorph TiO2 nanoparticles
      increased cell invasion. These differences seem to be due to the effects of
      different configurations of TiO2 nanoparticles. TiO2 may provide a new strategy
      for cancer treatment and more studies are needed.

PMID- 29657680
TI  - Evaluation of the Role of -137G/C Single Nucleotide Polymorphism (rs187238) and
      Gene Expression Levels of the IL-18 in Patients with Coronary Artery Disease.
AB  - Objectives: Interleukin-18 (IL-18) is a proinflammatory and proatherogenic
      cytokine, and its genetic variations may contribute to the development of
      coronary artery disease (CAD). We sought to investigate the role of -137G/C
      polymorphism and gene expression levels of IL-18 in patients with CAD. Methods:
      The study population included 100 patients with angiographically proven CAD and
      100 matched controls. Total RNA and DNA were extracted from leukocytes using
      appropriate kits. The genotype of -137G/C polymorphism and gene expression level
      of IL-18 was determined using allele-specific polymerase chain reaction (PCR) and
      real-time (RT)-PCR assay, respectively. Results: The genotypic and allelic
      distribution of IL-18 -137G/C polymorphism was not significantly different
      between the two groups (p > 0.050). Moreover, the -137G/C polymorphism did not
      increase the risk of CAD in dominant and recessive genetic models (p > 0.050).
      However, subgroup analysis of CAD patients revealed that the IL-18 -137G/C
      polymorphism was significantly associated with increased risk of CAD in
      hypertensive patients (odds ratio (OR) = 7.51; 95% confidence interval (CI): 1.24
      25.17; p = 0.019) and smokers (OR = 4.90; 95% CI: 1.21-19.70; p = 0.031) but not
      in the diabetic subpopulation (p = 0.261). The genotype distribution of IL-18 
      137G/C genetic polymorphism was significantly different among patients with one,
      two, and three stenotic vessels (p < 0.050). The gene expression level of IL-18
      was significantly higher in the CAD group than the control group (p < 0.001).
      Moreover, the carriers of CC genotype had significantly lower gene expression
      levels of IL-18 than carriers of GG genotype (p < 0.050). Conclusions: The 
      137G/C polymorphism of IL-18 may be associated with the CAD risk in hypertensive
      and smoker subgroup of CAD patients. The -137G/C polymorphism seems to play an
      important role in determining the severity of CAD. Increased IL-18 gene
      expression level is a significant risk factor for the development of CAD. The CC
      genotype of -137G/C polymorphism is associated with lower IL-18 gene expression
      levels.

PMID- 29657681
TI  - Outcomes of Isolated Antenatal Hydronephrosis at First Year of Life.
AB  - Objectives: To compare the grade of hydronephrosis between the antenatal and
      first postnatal ultrasound (US) and their clinical outcomes. Methods: This
      retrospective study included all cases of isolated hydronephrosis detected by
      antenatal US from August 2005 to February 2011. Hydronephrosis was classified
      based on the standard criteria into mild, moderate, or severe. Cases associated
      with other major congenital anomalies were excluded. All patients were followed
      up postnatally and outcomes available were analyzed at one year of age. Results:
      A total of 105 cases were included out of which 83 (79.0%) were males and 22
      (20.9%) were females with a median gestational age of 38 weeks. First postnatal
      US of 105 cases showed that 20 (19.0%) were free of hydronephrosis, 39 (37.1%)
      had mild, 29 (27.6%) moderate, and 17 (16.1%) had severe hydronephrosis. Half
      (50.4%) of hydronephrosis cases improved in their clinical presentation while
      13.3% showed deterioration and 36.3% remained the same. Almost half of all cases
      (52 cases) were diagnosed by US at the end of first year without any effect on
      renal function. Conclusions: Antenatal and postnatal US are sensitive tools for
      detecting hydronephrosis as well as for postnatal counseling. Fetal anatomy US is
      usually done at 18 weeks gestation and if this reveals any evidence of
      hydronephrosis, the patient is followed according to the severity. Postnatal US
      is not done routinely for cases where hydronephrosis resolves completely during
      pregnancy. Although newborns with antenatal hydronephrosis due to secondary
      causes are at greater risk for renal impairment, surgical intervention reserves
      renal function.

PMID- 29657682
TI  - The Relationship Between Prevalence of Antibiotics Resistance and Virulence
      Factors Genes of MRSA and MSSA Strains Isolated from Clinical Samples, West Iran.
AB  - Objectives: We sought to evaluate the relationship between the prevalence of
      antibiotics resistance and virulence factors genes in methicillin-resistant
      Staphylococcal aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) strains
      from clinical samples taken in west Iran. Methods: We performed a cross-sectional
      study using 100 MRSA and 100 MSSA samples isolated from clinical specimens. We
      used biochemical methods to identify the isolates, which were confirmed by the
      polymerase chain reaction (PCR) assay. Antibiotic susceptibility testing was
      performed using disk diffusion. PCR detected the presence of virulence factors,
      including enterotoxin genes, toxic shock syndrome toxin-1 (TSST-1), and
      exfoliative toxin. Results: The majority of MRSA isolates exhibited a high level
      of resistance to common antibiotics and susceptible to vancomycin, while most
      MSSA isolates were also resistant to erythromycin and ciprofloxacin. The
      prevalence of Staphylococcal enterotoxins (SEs) were reported 147 (73.5%). Among
      100 MRSA samples, 92 (92.0%) harbored SAg genes. The most frequent toxin gene was
      sea (45.0%) followed by sec (39.0%). Among 100 MSSA isolates, 89 (89.0%) harbored
      SAg genes and the most prevalent genes were sea (42.0%), sek (38.0%), sec
      (35.0%,), and TSST-1 (10.0%). The prevalence of TSST-1 and exfoliative toxin
      genes in MRSA samples were 12 (12.0%). The association of SAg genes with MRSA and
      MSSA isolates showed a high prevalence of enterotoxin seq, seg, and sei in MRSA
      than MSSA with a statistically significant difference (p < 0.050). Conclusions:
      The prevalence of MRSA and the association of pathogenic agents with antibiotics
      resistance genes can lead to the emergence of strains with higher pathogenicity
      and less susceptibility.

PMID- 29657683
TI  - Radiation Protection Knowledge, Attitude, and Practice (KAP) in Interventional
      Radiology.
AB  - Objectives: Due to increasing cardiac disease and its mortality rate, the
      frequency of cardiac imaging has grown and, as a result, interventional
      cardiologists potentially receive high radiation doses in cardiac examinations.
      This study aimed to assess the knowledge, attitude, and practice (KAP) level of
      radiation protection (RP) among interventional radiology staff in Iranian health
      care centers across the country. Methods: We used a validated questionnaire
      survey consisting of 30 multiple-choice questions to perform a cross-sectional
      study. Participants were healthcare personnel working professionally with
      radiation at different levels (i.e., secretary, radiology technologists, nurse,
      and physician). The questionnaire was divided into three sections to assess KAP
      regarding RP. Results: Significant differences exist in RP KAP mean scores based
      on educational age (p < 0.050). There was no significant difference in RP KAP
      mean scores when looking at sex, practice age, and hospital type (p > 0.050). We
      found a significant difference between RP KAP mean scores and different regions
      (p < 0.050). Conclusions: Educational and practice age, sex, type of hospital,
      and geographical region affect he KAP of interventional radiology staff regarding
      RP. Since many of the subjective radiation harms for both medical team and
      patients, this can be easily controlled and prevented; a checkup for personnel of
      interventional radiology departments, considering samples from different parts of
      the country with different levels of education, continuous training, and
      practical courses may help map the status of KAP. The results of this study may
      also help authorized health physics officers design strategic plans to enhance
      the quality of such services in radiation departments.

PMID- 29657684
TI  - Traditional and Complementary Medicine Use in Knee Osteoarthritis and its
      Associated Factors Among Patients in Northeast Peninsular Malaysia.
AB  - Objectives: We sought to determine the prevalence of traditional and
      complementary medicine (TCM) use for knee osteoarthritis and its associated
      factors among patients attending a referral hospital in an eastern coastal state
      of Malaysia. Methods: This cross-sectional study included 214 patients with knee
      osteoarthritis. A universal sampling method was applied to patients who attended
      the outpatient clinic in Hospital Universiti Sains Malaysia from May 2013 to
      October 2013. Participants were given a questionnaire to determine their
      sociodemographic information and a validated Bahasa Malaysia version of the
      Western Ontario and McMaster Universities Arthritis Index (WOMAC). This
      questionnaire was used to assess the severity of knee osteoarthritis (i.e., pain,
      stiffness, and disturbances in daily activity). Results: Over half (57.9%) of
      patients reported using TCM to treat knee osteoarthritis. Factors associated with
      TCM use were gender (odd ratio (OR) = 2.47; 95% confidence interval (CI): 1.28
      4.77), duration of knee osteoarthritis (OR = 1.51; 95% CI: 1.03-2.23), and the
      severity of knee pain (OR = 2.56; 95% CI: 1.71-3.86). Conclusions: The prevalence
      of TCM use among eastern Malaysian patients with knee osteoarthritis was high.
      Physicians caring for these patients should be aware of these findings so that
      inquiries regarding TCM use can be made and patients can be appropriately
      counseled.

PMID- 29657685
TI  - Nurses' Perceptions of Spirituality and Spiritual Care at Five Tertiary Care
      Hospitals in Riyadh, Saudi Arabia: A Cross-Sectional Study.
AB  - Objectives: To identify the perceptions towards spirituality and spiritual care
      among nurses at tertiary care hospitals in Riyadh, Saudi Arabia. Methods: A cross
      sectional study was conducted on nurses at five tertiary care hospitals in
      Riyadh. The data were collected using the Spirituality and Spiritual Care Rating
      Scale (SSCRS). Results: We recruited 978 nurses, of which 896 (91.6%) were
      female. The mean SSCRS score was 3.8+/-0.5 (the spirituality and spiritual care
      statements fell within the 'agree' category). A statistically significant
      difference was found only between perceptions of spirituality and spiritual care
      among nurses and their nursing experience duration. Conclusions: The findings of
      this study revealed that nurses were oriented to spirituality, and respected the
      importance of providing spiritual care to their patients. The nurses believed
      that spirituality exists in all religions and spiritual care means showing
      concern while treating the patients by focusing on respecting patients' religious
      beliefs.

PMID- 29657686
TI  - Extraskeletal Myxoid Chondrosarcoma of Nasopharynx: An Oncologic Entity Rarely
      Reported.
AB  - Extraskeletal myxoid chondrosarcoma (ESMC) is an extremely rare variant of
      chondrosarcoma accounting for less than 10% cases. It affects mainly the soft
      tissues of the proximal end of long bones. Its incidence in the head and neck
      region is less than 5%. This case presented in the nasopharynx, an exceedingly
      unusual site for ESMC in a 60-year-old female with left-sided nasal obstruction
      and occasional epistaxis of one-year duration. Biopsy from the nasopharyngeal
      mass was suggestive of low-grade chondrosarcoma. She underwent endoscopic
      resection of the tumor. Postoperative histopathology confirmed the diagnosis as
      myxoid chondrosarcoma of nasopharynx after performing a battery of
      immunohistochemical markers to rule out other possible differential diagnoses. We
      treated her with conformal adjuvant radiotherapy to a dose of 66 Gray in 33
      fractions given residual disease to which she responded well with significant
      symptomatic and radiological improvement. The patient has been on regular follow
      up for over two years without any evidence of recurrence or distant metastasis.
      This case is presented to highlight the extreme rarity, the clinicopathological
      findings of this disease, and to emphasize the role of radiotherapy as the
      primary adjuvant treatment affecting the final prognosis. A thorough review of
      the literature reveals that our case may be the second case of myxoid
      chondrosarcoma of nasopharynx ever reported in the world literature to date.

PMID- 29657687
TI  - Multiple Bilateral Ovarian Mature Cystic Teratomas with Ovarian Torsion: A Case
      Report.
AB  - Ovarian tumors are a common form of neoplasm in women. Mature cystic teratoma is
      the most common type, with a bilateral incidence of 8-15%. However, few cases are
      reported as bilateral and multiple. A rare case of bilateral multiple dermoid
      cysts in a 19-year-old female patient presented with abdominal pain of one-day
      duration. Her medical history was unremarkable. Ultrasonography showed multiple
      bilateral ovarian cystic masses. The patient underwent laparotomy. The masses
      were excised while preserving the remaining ovarian tissue. Histopathology
      confirmed the diagnosis of multiple mature cystic teratomas with no presence of
      malignant tissue.

PMID- 29657688
TI  - Concurrent Mastoid Cellulitis and Langerhans Cells Histiocytosis: ?A Challenging
      Diagnosis.
AB  - Langerhans cell histiocytosis (LCH) is a rare proliferative disorder, which
      commonly arises in the bone and may involve other systems. To date, the diagnosis
      of temporal bone LCH remains a challenge as it may masquerade as a common ear
      infection. We report a case of a child who presented to us with persistent
      bilateral ear discharge for four months and was not responding to treatment. Her
      condition subsequently worsened, with clinical features and radiological findings
      suggestive of mastoid cellulitis. Nevertheless, further histopathology study
      revealed LCH.

PMID- 29657689
TI  - Successful Management of Abdominal Pregnancy: Two Case Reports.
AB  - Abdominal pregnancy is a rare, life-threatening condition defined as pregnancy in
      the peritoneal cavity exclusive of tubal, ovarian, or intraligamentary locations.
      It can be primarily located in the peritoneal cavity or secondary to a ruptured
      ectopic pregnancy or tubal abortion. We present two cases of abdominal pregnancy,
      one primary and another secondary, both diagnosed and successfully managed in our
      institution. The first patient, a para 2 at 14 weeks gestation, presented with
      abdominal pain, distension, and dizziness, which had started four days prior. The
      initial radiological scan reported an intrauterine pregnancy with ascites, but a
      bedside ultrasound revealed an empty uterus and a viable pregnancy located in the
      Pouch of Douglas (POD). This was a secondary abdominal pregnancy managed
      successfully by laparotomy. The second patient, a para 3 + 4 miscarriages with
      seven weeks amenorrhea was admitted with an initial diagnosis of pregnancy of
      unknown location. She had a beta human chorionic gonadotropin level of 14 444
      mIU/mL. Diagnostic laparoscopy revealed a hemoperitoneum, bulky uterus, normal
      looking right and left adnexa, and a dense irregular bleeding tissue of around 3
      * 4 cm firmly attached to the POD. The histopathology report of the tissue
      retrieved from the POD confirmed products of conception. This case report
      supports the importance of awareness and high clinical suspicion for such a life
      threatening condition to avoid maternal morbidity and mortality. To the best of
      our knowledge, no previous cases of abdominal pregnancy have been reported in the
      UAE to date.

PMID- 29657690
TI  - An Unusual Case of Cardiac Mass.

PMID- 29657691
TI  - Do Lay People in Oman Know How to Perform Cardiopulmonary Resuscitation?

PMID- 29657692
TI  - Effectiveness of Positive Thinking Skills Training on the Hope and Quality of
      Life of Drug-Dependent People.
AB  - Background: The increase of hope and quality of life (QOL) can play a significant
      role in improving the mental health of drug addicts. Accordingly, the present
      study aimed to determine the effectiveness of positive thinking skills training
      on hope and QOL of drug-dependent people. Methods: The present study is a quasi
      experimental research with pre- and post-test design with the control group. The
      study population consisted of all men dependent on drugs who visited addiction
      treatment centers in Tehran, Iran, in 2016. Thirty subjects were selected using
      cluster sampling and were randomly assigned to control and experimental groups.
      The results were analyzed using SPSS. Findings: The mean scores of pre-test and
      post-test for hope were 31.67 +/- 6.47 and 49.68 +/- 10.69, for physical fitness
      were 17.01 +/- 4.21 and 22.84 +/- 4.98, for psychological health were 15.36 +/-
      3.45 and 20.98 +/- 3.32, for social relations were 7.80 +/- 2.34 and 10.96 +/-
      2.64, and for environmental health were 20.47 +/- 4.36 and 27.50 +/- 4.80,
      respectively, in experimental group (P < 0.050). Conclusion: It is recommended
      that addiction treatment centers teach positive thinking skills to drug-dependent
      people in order to increase their hope and QOL.

PMID- 29657693
TI  - The Effects of Acceptance and Commitment Therapy on Man Smokers' Comorbid
      Depression and Anxiety Symptoms and Smoking Cessation: A Randomized Controlled
      Trial.
AB  - Background: Besides physical problems, cigarette smoking is associated with a
      high prevalence of comorbid depression and anxiety symptoms. One of the reasons
      behind high post-cessation smoking lapse and relapse rates is inattentiveness to
      these symptoms during the process of cessation. The aim of this study was to
      examine the effects of acceptance and commitment therapy (ACT) on male smokers'
      comorbid depression and anxiety symptoms and smoking cessation. Methods: This two
      group pre-test-post-test randomized controlled trial was done on a random sample
      of seventy male smokers. Participants were randomly and evenly allocated to an
      intervention and a control group. Patients in these groups received either
      acceptance or commitment therapy or routine psychological counseling services
      include cognitive behavior therapy, respectively. Study data were collected
      through a demographic questionnaire, the Structural Clinical Interview (SCI) for
      Diagnostic and Statistical Manual of Mental Disorders-4th Edition (DSM-IV)
      disorders, Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and
      Micro Smokerlyzer carbon monoxide monitor. The SPSS software was employed to
      analyze the data. Findings: After the intervention, depression and anxiety scores
      and smoking cessation rate in the intervention group were respectively lower and
      higher than the control group (P < 0.050). Conclusion: ACT can significantly
      improve comorbid depression and anxiety symptoms and smoking cessation rate.
      Thus, it can be used to simultaneously manage depression, anxiety, and cigarette
      smoking.

PMID- 29657694
TI  - Pattern of Alcohol Consumption among Men Consumers in Kerman, Iran.
AB  - Background: Alcohol consumption is a potential risk factor with acute and chronic
      health consequences and social impacts, which is more prominent among men. There
      is no precise statistics on the scope of alcohol consumption in Iran; however,
      there is some evidences showing an increasing trend, particularly among young
      generation. In order to evaluate the scope of this issue in Kerman, a large city
      in the south-east of Iran, this exploratory study was designed to approach a
      group of people having an experience of alcohol use in 2014. Methods: Samples
      were recruited to the study using a snowball sampling. 200 eligible subjects were
      questioned about the type of alcohol consumed, frequency of use, and other
      factors associated with alcohol consumption. In order to maximize the validity of
      responses, data were collected through self-administered questionnaires.
      Findings: The main alcoholic drinks consumed by individuals were the homemade
      distillates (46%), wine (22%), beer (14%), distilled spirits (11%), and medical
      alcohol (7%), respectively. The majority of individuals participating in the
      study (73%) used mostly homemade drinks; moreover, 63%, 26%, 9%, and 2% of
      subjects took monthly or less, two to four times a month, two to three times a
      week, and at least four times a week, respectively. Only 2% of the subjects were
      heavy consumers of alcoholic beverages. Conclusion: Due to the lack of control
      over homemade alcoholic beverages, its high levels can be a huge potential risk.
      Furthermore, it seems that both factors of access and price to be very effective
      in the amount of alcoholics taken by individuals. Therefore, further studies in
      this area will help to reduce the harm caused by alcohol consumption.

PMID- 29657695
TI  - Effectiveness of Transactional Analysis Group Therapy on Addiction Intensity of
      Woman Patients Treated with Methadone.
AB  - Background: Addiction brings about severe and profound physical, psychological
      and social damages such as divorce, crime, and unemployment. The present study
      was to investigate the effectiveness of transactional analysis (TA) therapy on
      addiction intensity of woman patients treated with methadone. Methods: The
      research design was quasi-experimental with a pretest-posttest and a control
      group. The statistical population consisted of all the addicted women who
      referred to any drug rehabilitation center of Tehran, Iran, in 2016. They were
      selected using available sampling. Forty addicted patients were placed randomly
      in both the experimental and control groups. Addiction severity index (ASI) and
      demographic questionnaires were used. Group therapy using TA approach was
      executed on the experimental group for 10 sessions, each session for 2 hours (one
      session per week). Findings: The results of covariance analysis after controlling
      pretest showed that the difference between test and control group was significant
      for three subscales of psychological, drug abuse and alcohol consumption status
      (P < 0.001). The difference between test and control groups was significant
      considering the seven-variable centroid (P < 0.001). The difference in dimensions
      of addiction intensity between the two groups was significant (P < 0.001). Also,
      analysis of the variables separately showed significant differences in
      psychiatric condition, drug and alcohol use dimensions (P < 0.001). Conclusion:
      Based on these findings, it seems that group therapy using TA approach is
      effective in reducing addiction intensity of woman patients treated with
      methadone. Therefore, it can be concluded that TA group interventions account for
      76% of the changes in psychological status, 43% of the changes in drug abuse
      status, and 49% of the changes in alcohol consumption status in woman patients
      under methadone treatment.

PMID- 29657696
TI  - Comparing Effectiveness of Mindfulness-Based Relapse Prevention with Treatment as
      Usual on Impulsivity and Relapse for Methadone-Treated Patients: A Randomized
      Clinical Trial.
AB  - Background: Impulsivity is one of the causes of relapse that can affect treatment
      outcomes. Studies have shown that addiction treatments can reduce impulsivity in
      drug-dependent individuals. Studies also have suggested that mindfulness is
      associated with impulsivity. However, no study has investigated the effectiveness
      of the mindfulness-based intervention on impulsivity in opioid-dependent
      individuals. This study aimed to compare the effectiveness of mindfulness-based
      relapse prevention (MBRP) with treatment as usual (TAU) in terms of impulsivity
      and relapse for methadone-treated patients. Methods: The present randomized
      controlled clinical trial was performed in Kashan, Iran, in 2015. The study
      population was opioid-dependent patients referred to Maintenance Treatment
      Centers. Seventy patients were selected by random sampling and were assigned in
      two groups (MBRP and TAU) randomly. The participants of two groups filled out
      Barratt impulsivity scale (BIS-11) as a pre-test and 8 weeks later as post-test
      and 2 months later as a follow-up. Both groups received methadone-therapy. The
      MBRP group received 8 sessions of group therapy, while the control group did not
      receive any group psychotherapy session. Finally, data from 60 patients were
      analyzed statistically. Findings: The MBRP group had decreased impulsivity
      significantly (P < 0.001). The mean impulsivity score was 74.76 +/- 4.72 before
      intervention that was significantly decreased to 57.66 +/- 3.73 and 58.86 +/-
      3.57 after the intervention and follow-up (P < 0.001), respectively. In addition,
      significant differences were observed between MBRP and TAU groups for relapse
      frequency (P < 0.050). Conclusion: This study showed that MBRP compared to TAU
      can decrease the mean impulsivity score in opioid-dependent and reduce relapse
      probability. These findings suggest that MBRP is useful for opioid-dependent
      individuals with high-level impulsivity, and relapse prevention.

PMID- 29657697
TI  - Characterizing Mortality from Substance Abuse in Iran: An Epidemiological Study
      during March 2014 to February 2015.
AB  - Background: Drug abuse is a severe and chronic disorder that leaves morbidity,
      disability and premature mortality in the society. The study of death due to
      substance abuse provides useful information for local, national and international
      administrators. Thus, by identifying the factors that have an impact on overdose
      related mortality we can provide suitable intervention for vulnerable groups. The
      aim of this study was an investigation of mortality rate caused by consumption of
      narcotic and psychoactive substances in Iran. Methods: In this cross-sectional
      study, demographic and epidemiological data about all people whose cause of death
      was substance abuse in March 2014 to February 2015 were collected from Legal
      Medicine Organization (LMO). Finally, the information that was extracted from two
      checklists was analyzed by descriptive statistics. Findings: In this study, 2986
      cases died from substances abuse were evaluated. Most deaths have befallen in
      unmarried young men with mean age of 36.9 +/- 12.3, in the private locations. The
      mortality rate of drug abuse in the whole country was 38.4 per 1000000
      population. The proportion of mortality was higher in Iranian nationality and in
      people who had a diploma and less education. History of overdose, suicide,
      hospitalization in a psychiatric hospital, staying in prison and substance abuse
      in the family were investigated in the study population. Conclusion: The present
      study revealed that mortality rate from substance abuse is more among unmarried
      young men aged 30-39 years with low education level and also in the self-employed
      group. We suggest that policies should be taken to prevent these people from
      accessing and using the drug.

PMID- 29657698
TI  - The Effectiveness of the Harm Reduction Group Therapy Based on Bandura's Self
      Efficacy Theory on Risky Behaviors of Drug-Dependent Sex Worker Women.
AB  - Background: The aim of this study was to investigate the effectiveness of the
      harm reduction group therapy based on Bandura's self-efficacy theory on risky
      behaviors of sex workers in Kerman, Iran. Methods: A quasi-experimental two-group
      design (a random selection with pre-test and post-test) was used. A risky
      behaviors questionnaire was used to collect. The sample was selected among sex
      workers referring to drop-in centers in Kerman. Subjects were allocated to two
      groups and were randomly classified into two experimental and control groups. The
      sample group consisted of 56 subjects. The experimental design was carried out
      during 12 sessions, and the post-test was performed one month and two weeks after
      the completion of the sessions. The results were analyzed statistically.
      Findings: By reducing harm based on Bandura's self-efficacy theory, the risky
      behaviors of the experimental group, including injection behavior, sexual
      behavior, violence, and damage to the skin, were significantly reduced in the pre
      test compared to the post-test (P < 0.010). Conclusion: The harm reduction group
      therapy based on Bandura's self-efficacy theory can reduce the risky behaviors of
      sex workers.

PMID- 29657699
TI  - Review on the Implementation of the Islamic Republic of Iran about Tobacco
      Control, Based on MPOWER, in the Framework Convention on Tobacco Control by the
      World Health Organization.
AB  - Background: Smoking is the largest preventable cause of death in the world,
      killing nearly 6 million people annually. This article is an investigation of
      measures implemented laws in the Iran to study the proposed strategy of control
      and reduce tobacco use based on the monitor, protect, offer, warn, enforce and
      raise (MPOWER) policy. Methods: All laws approved by the Parliament along with
      the instructions on tobacco control prepared by the Ministry of Health and
      Medical Education, Ministry of Industry, Mine and Trade were collected and
      studied. Moreover, practical steps of Ministry of Health and other organizations
      were examined in this regard. Findings: Iranian Parliament after the adoption of
      the Framework Convention on Tobacco Control (FCTC) acts to create a comprehensive
      and systematic program for tobacco control legislation as a first step towards
      comprehensive national tobacco control and combat. In this law and its
      implementing guidelines and based on the strategy of MPOWER, specific implement
      is done to monitor tobacco use and prevention policies, protect people from
      tobacco smoke, offer help to quit tobacco use, warn about the dangers of tobacco,
      enforce bans on tobacco advertising, promotion and sponsorship and raise taxes on
      tobacco. However, the full objectives of the legislation have not achieved yet.
      Conclusion: According to Iran's membership in the FCTC and executive producer of
      tobacco control laws and regulations, necessary infrastructure is ready for a
      serious fight with tobacco use. In Iran, in comparison with developed countries,
      there is a huge gap between ratified laws and performing of laws.

PMID- 29657700
TI  - Misleading hepatitis B serology following Rho (D) immune globulin (human)
      injection and influenza vaccine.
AB  - Having a hepatitis B surface antibody (HBsAb) titre of more than 10 mIU/mL after
      hepatitis B vaccination is generally considered to confer immunity to hepatitis
      B. This case report discusses an unusual case of a false positive hepatitis B
      core total antibody (HBcAb) following administration of either Rho (D) immune
      globulin (Human) injection or influenza vaccine in a patriuent who was previously
      immunised against hepatitis B.

PMID- 29657701
TI  - Early prenatal diagnosis of parapagus conjoined twins.
AB  - Conjoined twinning occurs in 1/100 of monozygotic twins, 1/50,000 gestations and
      1/250,000 live births. It is the consequence of a division event at the primitive
      streak stage of the human embryonic development, about 13-14 days after
      fertilisation, in monochorionic monoamniotic gestations. A healthy pregnant
      woman, Gravida 2 Para 1, was admitted into our Fetal Medicine Unit to perform the
      first trimester ultrasound. A diagnosis of conjoined parapagus twinning based on
      ultrasound features was made at 11 weeks of gestation, and the couple decided to
      terminate the pregnancy. The ultrasound showed two independent skulls and hearts,
      a shared spine below the thoracic level, and a shared stomach. The pathological
      findings were slightly different, showing two independent stomachs draining into
      a common duodenum. The karyotype was 46 XY. Early prenatal ultrasound may provide
      a window to counsel the family and to offer an early termination of pregnancy.

PMID- 29657702
TI  - Rectal leiomyoma, a rare entity.
AB  - Rectal tumors are often encountered as an incidental finding on screening
      colonoscopy. As per the World Health Organization, they are categorized according
      to their histologic appearance. These include epithelial tumors, mesenchymal
      tumors and lymphomas. Of interest, in our case, are mesenchymal tumors. These are
      sub-classified into leiomyomas and gastrointestinal stromal tumors. Our case is a
      33-year old male who was diagnosed with a rectal leiomyoma. The uncommon
      incidence and subsequent management of a rectal leiomyoma in a male, make this
      case worthy for literature review.

PMID- 29657703
TI  - DETERMINING THE ELEMENTAL AND ISOTOPIC COMPOSITION OF THE PRESOLAR NEBULA FROM
      GENESIS DATA ANALYSIS: THE CASE OF OXYGEN.
AB  - We compare element and isotopic fractionations measured in solar wind samples
      collected by NASA's Genesis mission with those predicted from models
      incorporating both the ponderomotive force in the chromosphere and conservation
      of the first adiabatic invariant in the low corona. Generally good agreement is
      found, suggesting that these factors are consistent with the process of solar
      wind fractionation. Based on bulk wind measurements, we also consider in more
      detail the isotopic and elemental abundances of O. We find mild support for an O
      abundance in the range 8.75 - 8.83, with a value as low as 8.69 disfavored. A
      stronger conclusion must await solar wind regime specific measurements from the
      Genesis samples.

PMID- 29657704
TI  - Successful treatment of three synchronous primary malignant tumours-reflection on
      surgical, pathological and oncological aspects and decision making.
AB  - We report a case of a patient with triple synchronous primary malignancies
      (breast, colon, kidney) which has not been previously reported in the literature.
      A 70-year-old woman was diagnosed with invasive ductal carcinoma of the left
      breast with axillary lymph node metastasis. During the staging period, renal cell
      carcinoma on the left kidney and mucinous adenocarcinoma in the proximal colon
      were found. Since the breast tumour demonstrated favourable biology, aromatase
      inhibitor therapy had been started and simultaneous right colectomy and left
      nephrectomy was performed. Six months after the first diagnosis, left sector
      excision and axillary block dissection were performed. Adjuvant FEC chemotherapy
      was administered, followed by radiotherapy. During the 16-month follow-up period
      disease recurrence was not detected.

PMID- 29657705
TI  - Laparoscopic transhiatal resection of a large mid-esophageal diverticulum: a case
      report.
AB  - This is a description of transhiatal laparoscopic approach for mid-esophageal
      diverticulum. Traditionally mid-esophageal diverticula are approached by
      thoracotomy or thoracoscopy, with the laparoscopic technique being reserved for
      epiphrenic diverticula. A 78-year-old Caucasian female with a secondary
      dilatative ischemic cardiomyopathy presented with dysphagia, tenderness in the
      epigastrium and a considerable weight loss. A large mid-esophageal diverticulum
      was found on barium swallow and confirmed by CT scan. Underlying achalasia was
      recorded on manometry. The patient underwent diverticulectomy via transhiatal
      approach, followed by Heller myotomy and Dor fundoplication. Throughout the
      procedure auxiliary, esophagoscopic image was provided by interventional
      gastroenterologist due to a very narrow operating field and lack of orientation
      points. Based on our experience with this case, we propose transhiatal approach
      as a feasible alternative to thoracoscopy, in particular with patients who suffer
      from cardiac or pulmonary co-morbidities which make traditional techniques of
      high risk.

PMID- 29657706
TI  - Kimura's disease of the parotid gland with cutaneous features in a Caucasian
      female patient.
AB  - Kimura's disease is a rare disease of unknown aetiology, commonly presenting with
      slow-growing head and neck subcutaneous nodules, lymphadenopathy, eosinophilia
      and elevated immunoglobulin E. This report describes a very rare case of a 41
      year-old female, of White-British ethnicity, with a new diagnosis of Kimura's
      disease of the parotid gland and associated cutaneous features. The patient was
      investigated for 3 years before a diagnosis of Kimura's disease was reached. A
      superficial parotidectomy was undertaken and no recurrence was observed in the 20
      months following surgery. Kimura's disease is easily misdiagnosed, owing to lack
      of clinical awareness. This case report highlights the troubling symptomatology
      as well as complexities of diagnosis and management of Kimura's disease. A high
      level of clinical suspicion is required, for patients of any ethnicity and sex
      presenting with features consistent with the disease, in order for prompt
      diagnosis, investigation and management to be achieved.

PMID- 29657707
TI  - Abdominal tattoo can be useful to avoid a midline abdominal incision.
AB  - We report a case in which abdominal tattoo margins were modified and used to hide
      the surgical incision for desmoid tumour removal. Our patient is a 37-year-old
      female with history remarkable for atrial septal defect closure at the age of
      ten, but not for previous abdominal surgeries or trauma. A desmoid tumour
      diagnosis was made upon needle biopsy of the 5 * 4 cm2 mass confined to the
      rectus abdominis. Subsequently, tumour was resected with an incision through the
      tattoo upper margin and abdominal wall was reconstructed with primary fascial
      closure mesh reinforced. Excision was radical, scar inconspicuous and no
      incisional hernia, bulging, nor tumour recurrence were detected at 2-year follow
      up. This report highlights the fact that an abdominal tattoo might be considered
      as incision access instead of typical midline incision.

PMID- 29657708
TI  - Comparative approaches to gentrification: Lessons from the rural.
AB  - The epistemologies and politics of comparative research are prominently debated
      within urban studies, with 'comparative urbanism' emerging as a contemporary
      lexicon of urban studies. The study of urban gentrification has, after some
      delay, come to engage with these debates, which can be seen to pose a major
      challenge to the very concept of gentrification. To date, similar debates or
      developments have not unfolded within the study of rural gentrification. This
      article seeks to address some of the challenges posed to gentrification studies
      through an examination of strategies of comparison and how they might be employed
      within a comparative study of rural gentrification. Drawing on Tilly (Big
      structures Large Processes Huge Comparisons. New York: Russell Sage), examples of
      four 'strategies of comparison' are identified within studies of urban and rural
      gentrification, before the paper explores how 'geographies of the concept' and
      'geographies of the phenomenon' of rural gentrification in the United Kingdom,
      United States and France may be investigated using Latour's (Pandora's Hope.
      London: Harvard University Press) notion of 'circulatory sociologies of
      translation'. The aim of our comparative discussion is to open up dialogues on
      the challenges of comparative studies that employ conceptions of gentrification
      and also to promote reflections of the metrocentricity of recent discussions of
      comparative research.

PMID- 29657709
TI  - Comparative ruralism and 'opening new windows' on gentrification.
AB  - In response to the five commentaries on our paper 'Comparative approaches to
      gentrification: lessons from the rural', we open up more 'windows' on rural
      gentrification and its urban counterpart. First, we highlight the issues of
      metrocentricity and urbanormativity within gentrification studies, highlighting
      their employment by our commentators. Second, we consider the issue of
      displacement and its operation within rural space, as well as gentrification as a
      coping strategy for neoliberal existence and connections to more-than-human
      natures. Finally, we consider questions of scale, highlighting the need to avoid
      naturalistic conceptions of scale and arguing that attention could be paid to the
      role of material practices, symbolizations and lived experiences in producing
      scaled geographies of rural and urban gentrification.

PMID- 29657710
TI  - A comparison of spatial heterogeneity with local cluster detection methods for
      chronic respiratory diseases in Thailand.
AB  - BACKGROUND: The Centers for Disease Control and Prevention reported that deaths
      from chronic respiratory diseases (CRDs) in Thailand increased by almost 13% in
      2010, along with an increased burden related to the disease. Evaluating the
      geographical heterogeneity of CRDs is important for surveillance. Previous
      studies have indicated that socioeconomic status has an effect on disease, and
      that this can be measured with variables such as night-time lights (NTLs) and
      industrial density (ID). However, there is no understanding of how NTLs and ID
      correlate with CRDs. We compared spatial heterogeneity obtained by using local
      cluster detection methods for CRDs and by correlating NTLs and ID with CRDs.
      METHODS: We applied the spatial scan statistic in SaTScan, as well as local
      indices of spatial association (LISA), Getis and Ord's local Gi*(d) statistic,
      and Pearson correlation. In our analysis, data were collected on gender, age,
      household income, education, family size, occupation, region, residential area,
      housing construction materials, cooking fuels, smoking status and previously
      diagnosed CRDs by a physician from the National Socioeconomic Survey, which is a
      cross-sectional study conducted by the National Statistical Office of Thailand in
      2010. RESULTS: According to our findings, the spatial scan statistic, LISA, and
      the local Gi*(d) statistic revealed similar results for areas with the highest
      clustering of CRDs. However, the hotspots for the spatial scan statistic covered
      a wider area than LISA and the local Gi*(d) statistic. In addition, there were
      persistent hotspots in Bangkok and the perimeter provinces. NTLs and ID have a
      positive correlation with CRDs. CONCLUSIONS: This study demonstrates that all the
      statistical methods used could detect spatial heterogeneity of CRDs. NTLs and ID
      can serve as new parameters for determining disease hotspots by representing the
      population and industrial boom that typically contributes to epidemics.

PMID- 29636897
TI  - Monocytes isolated by positive and negative magnetic sorting techniques show
      different molecular characteristics and immunophenotypic behaviour.
AB  - Background: Magnetic sorting of cells, based on  microbead conjugated antibodies
      (Abs), employs positive as well as negative immunomagnetic separation methods,
      for isolation of a specific cell population. These microbeads are suggested to be
      nontoxic, biodegradable carriers conjugated to various antibodies. Isolation of
      cells through positive selection involves the attachment of antibody conjugated
      microbeads to the cells of interest, followed by their isolation in the presence
      of a strong magnetic field to obtain higher purity. Negative selection involves
      attachment of microbead conjugated antibodies to all other cell populations
      except the cells of interest, which remain untagged. In the present study, we
      compared the two methods for their effect on functional and immunophenotypic
      behavior of isolated CD14+ monocytes. Methods: Peripheral blood mononuclear cells
      (PBMCs) were isolated from blood collected from healthy volunteers by density
      gradient centrifugation. Human blood derived monocytes were isolated through
      positive selection and negative selection, making use of the appropriate monocyte
      isolation kit. Monocytes were then stimulated with lipopolysaccharide (LPS) and
      their activation and proliferation capacity were examined. The degradation or
      dissociation of cell-bound microbeads was also investigated. Results: We observed
      an impaired LPS sensitivity as well as poor activation and proliferation capacity
      upon stimulation by LPS in positively sorted CD14+ monocytes as compared to
      negatively sorted CD14+ monocytes. The attached microbeads did not degrade and
      remained attached to the cells even after 6 days of culture. Conclusions: Our
      results suggest that positively sorted CD14+ cells exhibit hampered functionality
      and may result in inaccurate analysis and observations in downstream
      applications. However, these cells can be used for immediate analytical
      procedures.

PMID- 29657713
TI  - Mid-upper-arm circumference based case-detection, admission, and discharging of
      under five children in a large-scale community-based management of acute
      malnutrition program in Nigeria.
AB  - Background: Severe acute malnutrition (SAM) threatens the lives of millions of
      children worldwide particularly in low and middle-income countries (LMICs).
      Community-based management of acute malnutrition (CMAM) is an approach to
      treating large numbers of cases of severe acute malnutrition (SAM) in a community
      setting. There is a debate about the use of mid-upper arm circumference (MUAC)
      for admitting and discharging SAM children. This article describes the experience
      of using MUAC for screening, case-finding, referral, admission, and discharge in
      a large-scale CMAM program delivered through existing primary health care
      facilities in Nigeria. Methods: Over one hundred thousand (n = 102,245)
      individual CMAM beneficiary records were collected from two of the eleven states
      (i.e. Katsina and Jigawa) that provide CMAM programming in Nigeria. The data were
      double entered and checked using EpiData version 3.2 and analyzed using the R
      language for data-analysis graphics. Results: The median MUAC at admission was
      109 mm. Among admissions, 37.4% (38,275) had a comorbidity recorded at admission
      and 7.4% (7537) were recorded as having developed comorbidity during the
      treatment. Analysis in the better performing state program in the most recent
      year for which data were available found that 87.1% (n = 13,273) of admitted
      cases recovered and were discharged as cured, 9.2% (n = 1396) defaulted and were
      lost to follow-up, 2.9% (n = 443) were discharged as non-recovered, 0.7% (n =
      104) were transferred to inpatient services, and 0.2% (n = 27) were known (died,
      to be dead or to have passed) during the treatment episode. The program met
      SPHERE minimum standards for treatment outcomes for therapeutic feeding programs.
      Factors associated with negative outcomes (default, non-recovery, transfer, and
      death) were distance between home and the treatment center; lower MUAC, diarrhea
      and cough at admission; or developing diarrhea, vomiting, fever, or cough during
      the treatment episode. Conclusions: This study confirms that MUAC can be used for
      both admitting and discharging criteria in CMAM programs with MUAC < 115 mm for
      admission and MUAC > = 115 mm or at discharge (a higher discharge threshold could
      be used). Long distances between home and treatment centers, lower MUAC at
      admission, or having diarrhea, vomiting, fever, or cough during the treatment
      episode were factors associated with negative outcome. Providing CMAM services
      closer to the community, using mobile and / or satellite clinics, counseling of
      mothers by health workers to encourage early treatment seeking behavior, and
      screening of patients at each patient visit for early detection and treatment of
      comorbidities are recommended.

PMID- 29657712
TI  - Recent advances in understanding the biology of marginal zone lymphoma.
AB  - There are three different marginal zone lymphomas (MZLs): the extranodal MZL of
      mucosa-associated lymphoid tissue (MALT) type (MALT lymphoma), the splenic MZL,
      and the nodal MZL. The three MZLs share common lesions and deregulated pathways
      but also present specific alterations that can be used for their differential
      diagnosis. Although trisomies of chromosomes 3 and 18, deletions at 6q23,
      deregulation of nuclear factor kappa B, and chromatin remodeling genes are
      frequent events in all of them, the three MZLs differ in the presence of
      recurrent translocations, mutations affecting the NOTCH pathway, and the
      transcription factor Kruppel like factor 2 ( KLF2) or the receptor-type protein
      tyrosine phosphatase delta ( PTPRD). Since a better understanding of the
      molecular events underlying each subtype may have practical relevance, this
      review summarizes the most recent and main advances in our understanding of the
      genetics and biology of MZLs.

PMID- 29657714
TI  - Non-typeable Haemophilus Influenzae detection in the lower airways of patients
      with lung cancer and chronic obstructive pulmonary disease.
AB  - Background: Chronic airway inflammation and hypersensitivity to bacterial
      infection may contribute to lung cancer pathogenesis. Previous studies have
      demonstrated that nontypeable Haemophilus influenzae (NTHi) is the most common
      colonizing bacteria in the lower airways of patients with COPD. The objective of
      this study was to determine the presence of NTHi and immunoglobulin
      concentrations in patients with lung cancer, COPD and controls. Methods: Serum
      and bronchial wash samples were collected from patients undergoing diagnostic
      bronchoscopy. Total IgE, IgG and specific NTHi IgG were measured by enzyme linked
      immunosorbent assay. Bronchial wash samples were examined for the presence of
      NTHi via PCR. Results: Out of the 60 patients: 20 had confirmed Lung Cancer, 27
      had COPD only and 13 were used as Controls. NTHi was detected in the lower
      airways of all three groups (Lung Cancer 20%; COPD 22% and Controls 15%). Total
      IgE was highest in Lung Cancer subjects followed by COPD and control subjects
      (mean +/- SD: 870 +/- 944, 381 +/- 442, 159 +/- 115). Likewise total IgG was
      higher in Lung cancer (Mean +/- SD: 6.99 +/- 1.8) patients compared to COPD (Mean
      +/- SD: 5.43 +/- 2). Conclusions: The lack of difference in NTHi and specific
      antibodies between the three groups makes it less likely that NTHi has an
      important pathogenetic role in subjects with Lung Cancer. However the detection
      of higher IgE antibody in Lung Cancer subjects identifies a possible mechanism
      for carcinogenesis in these subjects and warrants further study.

PMID- 29657715
TI  - Multimodal Underwater Adhesion Using Self-assembled Dopa-bearing ABA Triblock
      Copolymer Networks.
AB  - Self-assembled mechanically robust Dopa-bearing triblock copolymer networks
      improve underwater adhesion through both energy dissipation and interfacial
      bonding. Polymer networks that incorporate energy dissipating motifs could
      improve the performance of high-performance wet adhesives rather than only by
      interfacial bonds.

PMID- 29657716
TI  - Seasonal physiological dynamics of maturing female southern flounder
      (Paralichthys lethostigma).
AB  - Physiological information is rarely used in descriptions of maturity for managed,
      wild fish species; however, the use of physiological data holds great promise to
      provide important detail on the complexities of oocyte development and maturity.
      Investigating southern flounder (Paralichthys lethostigma)-an overfished
      commercial and recreational fishery resource-we examined pre-spawn physiological
      changes in females to provide further detail of the maturation process. Given
      that adults of this species complete maturation and spawn in unknown offshore
      locations, information on pre-spawn physiological changes is particularly
      informative for both size- and age-based patterns of maturity. We evaluated
      seasonal and ontogenetic changes in hormone concentrations in blood plasma that
      are commonly associated with sexual maturation, in addition to quantifying and
      classifying lipid stored in liver tissue. We found a strong positive relationship
      between body weight and lipid content during all months, as well as evidence for
      mobilization of lipids among larger females in September and October, presumably
      for gonadal development. Throughout the sampling period, the lipid content of
      smaller individuals was dominated by structural lipids (as opposed to storage
      lipids). In contrast, larger individuals possessed greater amounts of storage
      lipids. This suggests that larger, putatively maturing individuals were
      accumulating storage lipids for later production of vitellogenin. Females sampled
      for blood sex steroids and ovarian histology showed different testosterone and
      estradiol concentrations between putatively maturing and immature fish, and
      temporal variation with peaks in October and November. Overall, emerging patterns
      of liver lipid content and composition and blood steroid concentrations describe
      a multi-month maturation process that is often managed one dimensionally over
      short time periods. Insights from this work will improve our understanding of the
      life history of southern flounder, with the potential for better understanding of
      the dynamics of offshore spawning migration and informing subsequent species
      management.

PMID- 29657717
TI  - Closure of a bronchopleural fistula complicating cryoprobe biopsy of the lung.
AB  - Cryoprobe biopsies are routinely performed by the interventional pulmonologist.
      Diagnostic yields are larger, with complication rates that are equal to or lower
      than that of traditional forceps biopsies. We will specifically evaluate one
      instance where a cryoprobe biopsy led to an alveolo-pleural fistula that did not
      resolve with simple tube thoracostomy. An endobronchial valve was placed and
      successfully resolved the pneumothorax and persistent air leak.

PMID- 29657718
TI  - Endotracheal tube clamping and extracorporeal membrane oxygenation to resuscitate
      massive pulmonary haemorrhage.
AB  - Massive pulmonary haemorrhage is a life-threatening and difficult-to-manage
      condition. In certain circumstances, traditional approaches for haemoptysis may
      not be effective. Here, we report a 64-year-old man presenting with dyspnoea and
      leg oedema. He was diagnosed with microscopic polyangiitis due to positive
      perinuclear anti-neutrophil cytoplasmic antibody and other supportive evidence.
      His hospital course was complicated with massive pulmonary haemorrhage, which led
      to hypoxic respiratory failure, shock, and pulseless electrical activity.
      Extracorporeal membrane oxygenation (ECMO) was employed during cardiopulmonary
      resuscitation. To control blood loss from his lungs, we clamped the endotracheal
      tube for tamponade therapy. The tube was clamped for 15 h till the haemorrhage
      subsided. ECMO and ventilator support were successfully weaned off after 5 and 10
      days, respectively. Our favourable experience suggests that endotracheal tube
      clamping with ECMO support is a viable management option for life-threatening
      pulmonary haemorrhage.

PMID- 29657719
TI  - Inpatient diabetes management by specialized diabetes team versus primary service
      team in non-critical care units: impact on 30-day readmission rate and hospital
      cost.
AB  - Objective: We compared the cost-effectiveness of two inpatient diabetes care
      models: one offered by a specialized diabetes team (SDT) versus a primary service
      team (PST). Research design and methods: We retrospectively evaluated 756
      hospital admissions of patients with diabetes to non-critical care units over 6
      months. Out of 392 patients who met the eligibility criteria, 262 were matched
      1:1 based on the mean of the initial four blood glucose (BG) values after
      admission. Primary outcomes were 30-day readmission rate and frequency, hospital
      length of stay (LOS) and estimated hospital cost. Secondary outcomes included
      glycemic control and BG variability. Results: Diabetes complexity and in-hospital
      complications were significantly higher among patients treated by SDT versus PST.
      Thirty-day readmission rate to medical services was lower by 30.5% in the SDT
      group versus the PST group (P<0.001), while 30-day readmission rate to surgical
      services was 5% higher in the SDT group versus the PST group (P<0.05), but
      frequency of 30-day readmissions was lower (1.1 vs 1.6 times, P<0.05). LOS in
      medical services was not different between the two groups, but it was
      significantly longer in surgical services in SDT (P<0.05). However, LOS was
      significantly lower in patients who were seen by SDT during the first 24 hours of
      admission compared with those who were seen after that (4.7 vs 6.1 days,
      P<0.001). Compliance to follow-up was higher in the SDT group. These changes were
      translated into considerable cost saving. Conclusions: Inpatient diabetes
      management by an SDT significantly reduces 30-day readmission rate to medical
      services, reduces inpatient diabetes cost, and improves transition of care and
      adherence to follow-up. SDT consultation during the first 24 hours of admission
      was associated with a significantly shorter hospital LOS.

PMID- 29657720
TI  - Promising novel therapy with hydrogen gas for emergency and critical care
      medicine.
AB  - It has been reported that hydrogen gas exerts a therapeutic effect in a wide
      range of disease conditions, from acute illness such as ischemia-reperfusion
      injury, shock, and damage healing to chronic illness such as metabolic syndrome,
      rheumatoid arthritis, and neurodegenerative diseases. Antioxidant and anti
      inflammatory properties of hydrogen gas have been proposed, but the molecular
      target of hydrogen gas has not been identified. We established the Center for
      Molecular Hydrogen Medicine to promote non-clinical and clinical research on the
      medical use of hydrogen gas through industry-university collaboration and to
      obtain regulatory approval of hydrogen gas and hydrogen medical devices
      (http://www.karc.keio.ac.jp/center/center-55.html). Studies undertaken by the
      Center have suggested possible therapeutic effects of hydrogen gas in relation to
      various aspects of emergency and critical care medicine, including acute
      myocardial infarction, cardiopulmonary arrest syndrome, contrast-induced acute
      kidney injury, and hemorrhagic shock.

PMID- 29657721
TI  - Past, present, and future of Emergency General Surgery in the USA.
AB  - Emergency General Surgery (EGS) patients represent a unique group of acutely ill
      surgical patients at high risk for death and complications. Since the inception
      of EGS as a surgical subspecialty in the early 2000s, there have been significant
      developments to further define the scope of EGS as well as to advance data
      collection, performance measurement, and quality improvement. This includes
      defining the EGS cohort by diagnosis and procedure and by overall burden,
      benchmarking of EGS outcomes, and creation of quality improvement programs aimed
      at reducing the excess morbidity and mortality associated with EGS. Going forward
      there exists a need for a more modern approach to quality improvement. This may
      include the creation of an EGS data registry, the use of electronic medical
      records data, wearable device technology, and a focus on patient reported
      outcomes.

PMID- 29657722
TI  - A summary of the Japan septic disseminated intravascular coagulation study.
AB  - Over the past few decades, the large, international, randomized controlled trials
      of anticoagulant therapies for patients with sepsis have not yielded any
      improvement in mortality rates. However, in Japan, anticoagulant therapies are
      administered for sepsis patients with disseminated intravascular coagulation
      (DIC), but not for sepsis patients without DIC. Furthermore, epidemiological data
      regarding sepsis in Japan are scarce. Therefore, a nationwide multicenter
      retrospective observational study, the Japan Septic Disseminated Intravascular
      Coagulation (JSEPTIC DIC) study, was undertaken. The JSEPTIC DIC study enrolled
      42 intensive care units and included 3,195 patients with sepsis. The results of
      the JSEPTIC DIC study indicated the following: (i) anticoagulant therapy may be
      effective in sepsis-induced DIC patients at high risk for death, (ii) recombinant
      human soluble thrombomodulin administration and antithrombin supplementation are
      associated with survival benefits in patients with sepsis-induced DIC.

PMID- 29657723
TI  - Accuracy of the smaller superior mesenteric vein sign for the detection of acute
      superior mesenteric artery occlusion.
AB  - Aims: The smaller superior mesenteric vein (SMV) sign is a well-known computed
      tomography (CT) parameter for acute superior mesenteric artery (SMA) occlusion.
      This CT sign is potentially beneficial for the early diagnosis of acute SMA
      occlusion; however, few reports have documented this sign. The present study
      aimed to determine the accuracy of the smaller SMV sign for the detection of
      acute SMA occlusion. Methods: We retrospectively reviewed CT images from 20
      patients with acute SMA occlusion and 1,216 controls. We measured the external
      diameters of the SMV and SMA, and calculated the SMV/SMA diameter ratio. A ratio
      <=1 indicated a positive smaller SMV sign. Results: Of the 20 patients, 14 had
      the smaller SMV sign, whereas of the 1,216 controls, 88 had the smaller SMV sign.
      Of the 88 controls with a positive sign, 79 had apparent reasons for the
      decreased flow in the SMA and nine patients had no reason for the decreased flow.
      The sensitivity and specificity of the smaller SMV sign for acute SMA occlusion
      were 70% and 99.2%, respectively. Conclusion: The smaller SMV sign is an accurate
      and important CT parameter for the detection of acute SMA occlusion.

PMID- 29657724
TI  - Quality of dispatch-assisted cardiopulmonary resuscitation by lay rescuers
      following a standard protocol in Japan: an observational simulation study.
AB  - Aim: Bystander cardiopulmonary resuscitation (CPR) is essential for improving the
      outcomes of sudden cardiac arrest patients. It has been reported that dispatch
      assisted CPR (DACPR) accounts for more than half of the incidence of CPR
      undertaken by bystanders. Its quality, however, can be suboptimal. We aimed to
      measure the quality of DACPR using a simulation study. Methods: We recruited
      laypersons at a shopping mall and measured the quality of CPR carried out in our
      simulation. Dispatchers provided instruction in accordance with the standard
      DACPR protocol in Japan. Results: Twenty-three laypersons (13 with CPR training
      experience within the past 2 years and 10 with no training experience)
      participated in this study. The median chest compression rate and depth were
      106/min and 33 mm, respectively. The median time interval from placing the 119
      call to the start of chest compressions was 119 s. No significant difference was
      found between the groups with and without training experience. However, subjects
      with training experience more frequently placed their hands correctly on the
      manikin (84.6% versus 40.0%; P = 0.026). Twelve participants (52.2%, seven in
      trained and five in untrained group) interrupted chest compressions for 3-18 s,
      because dispatchers asked if the patient started breathing or moving. Conclusion:
      This current simulation study showed that the quality of DACPR carried out by lay
      rescuers can be less than optimal in terms of depth, hand placement, and
      minimization of pauses. Further studies are required to explore better DACPR
      instruction methods to help lay rescuers perform CPR with optimal quality.

PMID- 29657725
TI  - Adherence rate of quality-of-care indicators for Staphylococcus aureus bacteremia
      is extremely low in Japanese emergency and critical care departments: a
      multicenter retrospective observational study.
AB  - Aim: Staphylococcus aureus bacteremia causes significant morbidity and mortality
      and requires specific management to prevent complications. Most studies
      evaluating quality of care have been carried out in Europe and North America, and
      accurate epidemiological data are lacking in Asia. We aimed to describe the
      epidemiology and evaluate the quality of care for S. aureus bacteremia in Japan.
      Methods: From February 2011 to January 2014, we undertook a multicenter
      retrospective observational study in 10 departments of emergency and critical
      care in Japan. We included 118 hospitalized adult patients with S. aureus
      bacteremia and evaluated three quality-of-care indicators: follow-up blood
      culture, treatment duration, and echocardiography. Results: The mean age of the
      patients was 63.5 +/- 17.0 years. The major source of bacteremia was pneumonia (n
      = 22, 19%), followed by skin and soft tissue infection (n = 18, 15%). Thirty
      patients (25%) died in the hospital. Follow-up blood culture was performed in
      21/112 patients (19%). The duration of antimicrobial treatment was sufficient in
      49/87 patients (56%). Echocardiography for patients with clinical indication was
      undertaken in 39/59 patients (66%). Any of the three indicators were inadequate
      in 101/118 (86%). Conclusion: The rate of adequate care for S. aureus bacteremia
      is low in Japan. The low adherence rate for follow-up blood culture was
      particularly notable. Staphylococcus aureus bacteremia can be an important target
      of quality improvement interventions.

PMID- 29657726
TI  - High-dose steroid therapy for acute respiratory distress syndrome lacking common
      risk factors: predictors of outcome.
AB  - Aim: Acute respiratory distress syndrome (ARDS) is a life-threatening lung
      disease that usually occurs in patients with the underling risk factors that
      triggers lung inflammation. We sometimes encounter patients with ARDS lacking
      common risk factors. Recent studies have indicated the effectiveness of
      corticosteroids for this cohort. However, the characteristics of survivors with
      ARDS who lack common risk factors, and who received high-dose methylprednisolone
      pulse therapy (MPPT), are not known. Methods: We undertook a retrospective study
      of patients with ARDS lacking common risk factors, who received i.v. MPPT for 3
      days. The patients (n = 46) were classified into two groups, survivors (n = 23)
      and non-survivors (n = 23), based on their survival at 60 days after the
      initiation of MPPT, and their clinical and radiological parameters were
      evaluated. Results: The patient characteristics and disease severity of the two
      groups were comparable. The percentage of consolidation/(ground-glass attenuation
      [GGA] + consolidation) on the chest computed tomography scans of survivors was
      significantly lower than that of non-survivors (survivors, 5.63% [2.31-13.8]
      versus non-survivors, 27.2% [5.97-41.4]; P = 0.01). In the stratified analysis,
      the percentage of consolidation/(GGA + consolidation) was significantly
      associated with 60-day survival. Conclusions: Our results show that the
      percentage of consolidation/(GGA + consolidation) on the chest CT scans is an
      independent prognostic factor for patients with ARDS lacking common risk factors
      after MPPT.

PMID- 29657727
TI  - Preoperative fluid restriction for trauma patients with hemorrhagic shock
      decreases ventilator days.
AB  - Aim: In recent years, with the concept of damage control resuscitation,
      hemostasis and preoperative fluid restriction have been carried out, but there is
      controversy regarding the effectiveness of fluid restriction. Methods: From April
      2007 to March 2013, 101 trauma patients presented with hemorrhagic shock
      (systolic blood pressure <=90 mmHg) at the prehospital or emergency department
      and were admitted to Hyogo Emergency Medical Center (Hyogo, Japan). They
      underwent emergency hemostasis by surgery and transcatheter arterial
      embolization. We compared two groups in a historical cohort study, the aggressive
      fluid resuscitation (AR) group, which included 59 cases treated in the period
      April 2007-March 2010, and the fluid restriction (FR) group, which included 42
      cases treated in the period April 2010-March 2013. Results: There was no
      difference between both groups in patient background (heart rate, 110 b.p.m.;
      systolic blood pressure, 70 mmHg). The Injury Severity Score was 34 (AR) versus
      38 (FR) (not significant). Preoperative infusion volume of crystalloid
      significantly decreased, from 2310 mL (AR) to 1025 mL (FR) (P <= 0.01). There was
      no difference in mortality (36% [AR] versus 41% [FR]). Ventilator days
      significantly decreased, from 8.5 days (AR) to 5.5 days (FR) (P = 0.02).
      Conclusions: Preoperative fluid restriction for trauma patients with hemorrhagic
      shock did not improve mortality, but it decreased ventilator days by reducing the
      perioperative plus water balance and it might contribute to perioperative
      intensive care.

PMID- 29657729
TI  - Risk factors for prolonged mechanical ventilation in patients with severe
      multiple injuries and blunt chest trauma: a single center retrospective case
      control study.
AB  - Aim: Blunt chest trauma is common and is associated with morbidity and mortality
      in patients with multiple injuries, frequently requiring invasive mechanical
      ventilation. The aim of this study was to elucidate risk factors for prolonged
      mechanical ventilation (PMV). Methods: Consecutive adult patients with multiple
      severe injuries and blunt chest trauma who treated in Chiba Emergency Medical
      Center (Chiba, Japan) between January 2008 and December 2015 were enrolled in
      this retrospective chart-review study. According to ventilatory time, the
      patients were divided into PMV (>=7 days) and shortened mechanical ventilation
      (SMV; <7 days) groups. Thoracic Trauma Severity Score (TTSS) was calculated. To
      identify risk factors for PMV, univariate and multivariate logistic analyses and
      receiver operating characteristic analysis were carried out. Results: Eighty-four
      and 49 patients were assigned to PMV and SMV groups, respectively. Compared with
      the SMV group, the PMV group had a significantly larger number of fractured ribs
      (P < 0.01), higher rate of severe Glasgow Coma Scale (GCS <=8) (P < 0.05) and
      flail chest (P < 0.001), higher TTSS (P < 0.001), or longer intensive care unit
      and hospital stay (both P < 0.001). Logistic analysis showed that severe GCS
      (odds ratio [OR] = 4.6, P < 0.01), flail chest (OR = 3.0, P < 0.05), and TTSS (OR
      = 1.2; P < 0.01) were independent significant risk factors. Receiver operating
      characteristic analyses showed that the area under the curves for TTSS, flail
      chest, and severe GCS were 0.74, 0.70, and 0.58, respectively. When the three
      factors were combined, the area under the curve increased to 0.8. Conclusion:
      Severe GCS (<=8), flail chest, or TTSS may be independent risk factors. Combining
      the three risk factors could provide high predictive performance for PMV.

PMID- 29657728
TI  - Can we predict delayed undesirable events after blunt injury to the torso
      visceral organs?
AB  - Aim: Blunt injuries to visceral organs have the potential to lead to delayed
      pseudoaneurysm formation or organ rupture, but current trauma and surgical
      guidelines do not recommend repetitive imaging. This study examined the incidence
      and timing of delayed undesirable events and established advisable timing for
      follow-up imaging and appropriate observational admission. Methods: Patients with
      blunt splenic (S), liver (L), or kidney (K) injury treated with non-operative
      management (NOM) in our institution were included and retrospectively reviewed.
      Results: From January 2013 to January 2017, 57 patients were admitted with
      documented blunt visceral organ injuries and 22 patients were excluded. Of 35
      patients (L, 10; S, 17; K, 6; L & S, 1; S & K, 1) treated with NOM, 14 (L, 4; S,
      9; K, 1) patients underwent transcatheter arterial embolization. Delayed
      undesirable events occurred in four patients: three patients with splenic
      pseudoaneurysm on hospital day 6-7 and one patient with splenic delayed rupture
      on hospital day 7. The second follow-up computed tomography scan carried out 1-2
      days after admission did not show any significant findings that could help
      predict undesirable results of delayed events. The patients with delayed events
      had longer continuous abdominal pain than that of event-free patients (P = 0.04).
      Conclusions: Undesirable delayed events were recognized on follow-up computed
      tomography scans in 11.4% of NOM patients at hospital day 6-7 and tended to be
      associated with high-grade splenic injuries and continuous symptoms. Repetitive
      screening of these patients 6-7 days after injury might be warranted because of
      the potential risk of delayed events.

PMID- 29657730
TI  - Lemierre's syndrome presented with acute pancreatitis.
AB  - Case: Lemierre's syndrome is a rare clinical condition that is characterized by
      infected internal jugular vein thrombosis with metastatic septicemia. The most
      common causative agent is Fusobacterium necrophorum. A previously healthy 37-year
      old woman presented to our emergency department with nausea, vomiting, and
      diarrhea. She was admitted to the general practice unit with a diagnosis of acute
      pancreatitis then was subsequently transferred to the intensive care unit due to
      shock. Physical examination revealed tenderness on right side of the neck. Blood
      cultures were remarkable for F. necrophorum. Clinical symptoms led to subsequent
      ultrasound and computed tomography scan of the neck, confirming internal jugular
      vein thrombosis. Outcome: The patient was treated with antibiotics for 6 weeks.
      Anticoagulation therapy was initiated. Conclusion: We report a case of Lemierre's
      syndrome that presented as acute pancreatitis. The high index of suspicion of
      this disease is important for early diagnosis.

PMID- 29657731
TI  - Coin pica-induced gastric perforation resulting from ingestion of 1,894 coins, 8
      kg in total: case report and review of published works.
AB  - Case: Pica is common among patients with psychiatric disorders, but only a few
      cases regarding coin pica have been reported. A 51-year-old man with depression
      complaining of fatigue was found to have numerous coins in the esophagus and the
      stomach on X-rays. He had a peritoneal sign and underwent an emergency
      laparotomy. Outcome: The surgical findings showed perforation on the anterior
      wall of the gastric body and coins in the stomach, which were removed manually,
      followed by an omental patch. Residual coins in the esophagus were removed by
      endoscopy. The coins totaled 1,894, weighing 8,076 grams. The patient was then
      diagnosed as schizophrenic. He was asymptomatic for metal toxicity and was
      finally transferred to a psychiatric hospital. Conclusion: This pica case is the
      first to show coin pica can lead to gastric perforation, and also reports the
      largest amounts of coins ingested by a person to date.

PMID- 29657732
TI  - Two cases of spontaneous cervical epidural hematoma without back or neck pain in
      elderly Japanese men.
AB  - Cases: Spontaneous spinal epidural hematoma (SSEH) is an uncommon disease. Most
      SSEH cases involve back and/or neck pain. We report the cases of two men who
      experienced SSEH with dysstasia but without back or neck pain. Outcomes: This
      study presents two cases involving elderly Japanese men who visited an emergency
      department because of sudden dysstasia without back or neck pain. The results of
      the neurological examinations revealed ataxic gait. Cervical spinal epidural
      hematomas were observed by computed tomography and magnetic resonance imaging.
      One patient underwent hematoma removal and decompression by corpectomy, whereas
      the other patient received conservative treatment and observation. The patients
      were discharged without sequelae. Conclusion: Spinal epidural hematomas are
      difficult to diagnose, and a delayed diagnosis can adversely affect the patient's
      quality of life. These hematomas should be considered in the differential
      diagnosis of cerebrovascular diseases.

PMID- 29657733
TI  - Contrast medium-induced transient severe leukopenia.
AB  - Case: Contrast medium-induced transient leukopenia is very rare. Here, we report
      a case of a 73-year-old man diagnosed with contrast media-induced transient
      leukopenia. The patient underwent abdominal contrast-enhanced computed
      tomography, where he was given non-ionic iodinated contrast medium i.v. His
      medical history included an allergic reaction to a different contrast medium. One
      hour later, the patient was admitted to the emergency department complaining of
      chest discomfort. He had leukopenia and a fever (temperature of 38.9 degrees C).
      Complete blood count showed a white blood cell count of 930/MUL and an absolute
      neutrophilic count of 232/MUL. Outcome: The patient was given i.v. antibiotics
      and 5 mg chlorpheniramine maleic acid, 20 mg famotidine, and 125 mg
      methylprednisolone. The patient's white blood cell count recovered the next day,
      and he was discharged after 2 days of hospitalization. Conclusion: We diagnosed
      the patient with contrast media-induced transient leukopenia, which is a rare
      phenomenon.

PMID- 29657734
TI  - Treatment of a patient with acute aortic dissection using extracorporeal
      cardiopulmonary resuscitation after an out-of-hospital cardiac arrest: a case
      report.
AB  - Case: Circulatory support using veno-arterial extracorporeal membrane oxygenation
      for aortic disease is conventionally contraindicated. In this case, a 66-year-old
      man experienced cardiopulmonary arrest caused by acute aortic dissection. When
      exercising in the gym, he experienced chest discomfort, so the staff immediately
      called an ambulance. While in the ambulance, he experienced cardiopulmonary
      arrest. His initial electrocardiogram showed ventricular fibrillation. At the
      emergency department, we immediately performed extracorporeal cardiopulmonary
      resuscitation. We suspected acute coronary syndrome, so coronary angiography was
      carried out. Enlargement of ascending aorta was noted. Whole-body enhanced
      computed tomography was subsequently performed, leading to a final diagnosis of
      acute aortic dissection. Outcome: Emergency ascending aorta prosthesis
      implantation was performed. The patient received intensive care and was
      discharged on day 49 of hospitalization. His cerebral performance category score
      was 4 at discharge. Conclusion: This case suggests that veno-arterial
      extracorporeal membrane oxygenation may be used for patients with aortic
      dissection presenting with cardiac arrest.

PMID- 29657735
TI  - Necrotizing enterocolitis associated with Clostridium butyricum in a Japanese
      man.
AB  - Case: Necrotizing enterocolitis (NEC) caused by Clostridium butyricum is common
      in neonates; however, a case of NEC in adults has not been previously reported.
      An 84-year-old Japanese man developed C. butyricum-related NEC during
      hospitalization for treatment of stab wounds to the left side of the neck and
      lower abdomen, without organ damage, and concomitant pneumonia. Outcome: The
      patient developed acute onset of emesis accompanied by shock during his
      admission; partial resection of the small intestine was carried out due to
      necrosis. Pathologic findings showed mucosal necrosis and extensive vacuolation
      with gram-positive rods in the necrotic small intestine. Blood culture tests
      revealed C. butyricum infection. The patient's condition improved after the
      surgery. He was moved to a rehabilitation hospital on day 66. Conclusion: This
      study suggests that hospitalized adult patients who receive antibiotic treatment
      are at risk for NEC.

PMID- 29657736
TI  - A new mutation of congenital methemoglobinemia exacerbated after methylene blue
      treatment.
AB  - Case: Methylene blue is useful for the treatment of methemoglobinemia. However,
      even after the patient's methemoglobin (metHb) rate has improved, careful
      observation is important because they could have undiagnosed congenital
      methemoglobinemia. In this case, a 67-year-old man underwent gastrointestinal
      endoscopy with the use of lidocaine for local anesthesia. During the examination,
      he complained of dyspnea and had low SpO2 despite normal PaO2 and SaO2. He was
      transferred to our department as a suspected case of acquired methemoglobinemia.
      Outcome: The patient's metHb level was 26.2%. We administered methylene blue i.v.
      and his metHb level subsequently decreased to 1.6%. However, his metHb level
      gradually increased to 18.2%, and we suspected that he had congenital
      methemoglobinemia. We administered riboflavin and ascorbic acid orally, and his
      metHb level decreased to 6.4%. We also obtained genomic DNA from the patient and
      identified a novel variant of CYB5R3. Conclusion: We report a novel variant of
      congenital methemoglobinemia that deteriorated after methylene blue treatment.

PMID- 29657737
TI  - Flunitrazepam overdose induces brilliant-blue gastric fluid.

PMID- 29657739
TI  - An atypical presentation of a pericardial cyst.
AB  - A pericardial cyst is a benign and rare congenital anomaly. The presentation of
      pericardial cysts varies with the extent of mediastinal involvement. Complaints
      can include dyspnea, pleuritic chest pain and systemic symptoms; however, the
      majority are asymptomatic. Imaging modalities such as MRI, CT and X-ray can
      visualize the cysts. Treatment approach includes aspiration or surgical
      resection. We describe an atypical presentation of a pericardial cyst and
      subsequent treatment and recommendations for these rare anomalies.

PMID- 29657740
TI  - Mechanical prosthetic heart valves: here to stay!

PMID- 29657741
TI  - A curious case of idiopathic subcutaneous emphysema.

PMID- 29657738
TI  - Lupus community panel proposals for optimising clinical trials: 2018.
AB  - Formidable impediments stand in the way of treatment development for lupus. These
      include the unwieldy size of current trials, international competition for scarce
      patients, complex outcome measures and a poor understanding of these outcomes in
      the world at large. The heterogeneity of the disease itself coupled to
      superimposition of variegated background polypharmacy has created enough
      immunological noise to virtually ensure the failure of lupus treatment trials,
      leaving an understandable suspicion that at least some of the results in testing
      failed drugs over the years may not have been negative, but merely
      uninterpretable. The authors have consulted with many clinical trial
      investigators, biopharmaceutical developers and stakeholders from government and
      voluntary sectors. This paper examines the available evidence that supports
      workable trial designs and proposes approaches to improve the odds of completing
      interpretable treatment development programs for lupus.

PMID- 29657742
TI  - Quantifying the relative effects of environmental and direct transmission of
      norovirus.
AB  - Norovirus is a common cause of outbreaks of acute gastroenteritis in health- and
      child-care settings, with serial outbreaks also frequently observed aboard cruise
      ships. The relative contributions of environmental and direct person-to-person
      transmission of norovirus have hitherto not been quantified. We employ a novel
      mathematical model of norovirus transmission, and fit the model to daily
      incidence data from a major norovirus outbreak on a cruise ship, and examine the
      relative efficacy of potential control strategies aimed at reducing environmental
      and/or direct transmission. The reproduction number for environmental and direct
      transmission combined is [Formula: see text] [6.1,9.5], and of environmental
      transmission alone is [Formula: see text] [0.9,2.6]. Direct transmission is
      overwhelmingly due to passenger-to-passenger contacts, but crew can act as a
      reservoir of infection from cruise to cruise. This is the first quantification of
      the relative roles of environmental and direct transmission of norovirus. While
      environmental transmission has the potential to maintain a sustained series of
      outbreaks aboard a cruise ship in the absence of strict sanitation practices,
      direct transmission dominates. We find that intensive promotion of good hand
      washing practices may prevent outbreaks. Isolation of ill passengers and cleaning
      are beneficial, but appear to be less efficacious at outbreak control.

PMID- 29657743
TI  - Rapid recalibration of speech perception after experiencing the McGurk illusion.
AB  - The human brain can quickly adapt to changes in the environment. One example is
      phonetic recalibration: a speech sound is interpreted differently depending on
      the visual speech and this interpretation persists in the absence of visual
      information. Here, we examined the mechanisms of phonetic recalibration.
      Participants categorized the auditory syllables /aba/ and /ada/, which were
      sometimes preceded by the so-called McGurk stimuli (in which an /aba/ sound, due
      to visual /aga/ input, is often perceived as 'ada'). We found that only one trial
      of exposure to the McGurk illusion was sufficient to induce a recalibration
      effect, i.e. an auditory /aba/ stimulus was subsequently more often perceived as
      'ada'. Furthermore, phonetic recalibration took place only when auditory and
      visual inputs were integrated to 'ada' (McGurk illusion). Moreover, this
      recalibration depended on the sensory similarity between the preceding and
      current auditory stimulus. Finally, signal detection theoretical analysis showed
      that McGurk-induced phonetic recalibration resulted in both a criterion shift
      towards /ada/ and a reduced sensitivity to distinguish between /aba/ and /ada/
      sounds. The current study shows that phonetic recalibration is dependent on the
      perceptual integration of audiovisual information and leads to a perceptual shift
      in phoneme categorization.

PMID- 29657744
TI  - Studying the association complex formation of atomoxetine and fluvoxamine with
      eosin Y and its application in their fluorimetric determination.
AB  - A simple, sensitive and non-extractive spectrofluorimetric method has been
      developed and validated for the determination of two psychoanaleptic drugs,
      atomoxetine and fluvoxamine, in pure forms and pharmaceutical dosage forms. The
      proposed method is based on the formation of binary complexes between eosin Y and
      the studied drugs in the presence of a Teorell-Stenhagen buffer. The quenching of
      the native fluorescence of eosin Y due to complex formation with the studied
      drugs was measured spectrofluorimetrically at 545 nm after excitation at 302 nm.
      At the optimum reaction conditions, the fluorescence quenching values (DeltaF)
      and concentrations were rectilinear over the concentration ranges of 0.2-2.2 and
      0.3-2.2 ug ml-1 for atomoxetine and fluvoxamine, respectively. The developed
      method was successfully applied for the determination of the studied drugs in
      their pharmaceutical formulations with average percentage recoveries of 100.13 +/
      0.66 and 99.69 +/- 0.44 for atomoxetine and fluvoxamine, respectively (n = 5),
      without interference from common excipients.

PMID- 29657745
TI  - Optimal random search using limited spatial memory.
AB  - Levy walks are known to be efficient movements because Levy walkers search wide
      areas while restricting returns to previously visited sites. A self-avoiding walk
      (SAW) is a series of moves on a lattice that visit the same place only once. As
      such, SAWs can also be effective search algorithms. However, it is not realistic
      that foragers memorize many visited positions for a long time. In this work, we
      investigated whether foragers performed optimal searches when having limited
      memory. The agent in our model followed SAWs to some extent by memorizing and
      avoiding visited places. However, the agent lost its memory after a while. In
      that situation, the agent changed its reactions to visited patches by considering
      global trail patterns based on local memorized information. As a result, we
      succeeded in making the agent occasionally produce ballistic walks related to
      power-law tailed movements across some ranges.

PMID- 29657746
TI  - A framework for estimating the determinants of spatial and temporal variation in
      vital rates and inferring the occurrence of unobserved extreme events.
AB  - We develop a general framework that combines long-term tag-recapture data and
      powerful statistical and modelling techniques to investigate how population,
      environmental and climate factors determine variation in vital rates and
      population dynamics in an animal species, using as a case study the population of
      brown trout living in Upper Volaja (Western Slovenia). This population has been
      monitored since 2004. Upper Volaja is a sink, receiving individuals from a source
      population living above a waterfall. We estimate the numerical contribution of
      the source population on the sink population and test the effects of temperature,
      population density and extreme events on variation in vital rates among 2647
      individually tagged brown trout. We found that individuals dispersing downstream
      from the source population help maintain high population densities in the sink
      population despite poor recruitment. The best model of survival for individuals
      older than juveniles includes additive effects of birth cohort and sampling
      occasion. Fast growth of older cohorts and higher population densities in 2004
      2005 suggest very low population densities in the late 1990s, which we
      hypothesize were caused by a flash flood that strongly reduced population size
      and created the habitat conditions for faster individual growth and transient
      higher population densities after the extreme event.

PMID- 29657747
TI  - Norm compliance affects perceptual decisions through modulation of a starting
      point bias.
AB  - Adaptive decisions in social contexts depend on both perceptual information and
      social expectations or norms. These are potentially in conflict when certain
      choices are beneficial for an individual, but societal rules mandate a different
      course of action. To resolve such a conflict, the reliability of information has
      to be balanced against potentially deleterious effects of non-compliance such as
      ostracism. In this study, we systematically investigated how interactions between
      perceptual and social influences affect decision-relevant cognitive processes. In
      a direction-of-motion discrimination task, participants received perceptual
      information alongside information on other players' choices. In addition, we
      created conflict scenarios where players' choices affected other participants'
      monetary rewards dependent on whether their choices were in line or against the
      opinion of the other players. Importantly, we altered the strength of this
      manipulation in two separate experiments by contrasting motivations of either
      preventing harm or providing a benefit to others. Behavioural analyses and
      computational models of perceptual decisions showed that participants
      successfully integrated perceptual with social information. Participants'
      reliance on social information was effectively modulated in conflict situations.
      Critically, these effects were augmented when the strength of social norms was
      increased, indexing conditions under which social norms effectively influence
      decisions. These results inform theories of social influence by providing an
      account of how higher order goals like social norm compliance affect perceptual
      decisions.

PMID- 29657748
TI  - A study of laser surface treatment in bonded repair of composite aircraft
      structures.
AB  - Surface pre-treatment is one of the key processes in bonded repair of aircraft
      carbon fibre reinforced polymer composites. This paper investigates the surface
      modification of physical and chemical properties by laser ablation and
      conventional polish treatment techniques. Surface morphology analysed by laser
      scanning confocal microscopy and scanning electron microscopy showed that a laser
      treated surface displayed higher roughness than that of a polish-treated
      specimen. The laser-treated laminate exhibited more functional groups in the form
      of O 1 s/C 1 s atomic ratio of 30.89% for laser-treated and 20.14% for polish
      treated as evidenced by X-ray photoelectron spectroscopy observation. Contact
      angle goniometry demonstrated that laser treatment can provide increased surface
      free energy and wettability. In the light of mechanical interlocking, molecular
      bonding and thermodynamics theories on adhesion, laser etching process displayed
      enhanced bonding performance relative to the polishing surface treatment. These
      properties resulted in an increased single lap shear strength and a cohesive
      failure mode for laser etching while an adhesive failure mode occurred in polish
      treated specimen.

PMID- 29657749
TI  - Aerodynamic efficiency of a bioinspired flapping wing rotor at low Reynolds
      number.
AB  - This study investigates the aerodynamic efficiency of a bioinspired flapping wing
      rotor kinematics which combines an active vertical flapping motion and a passive
      horizontal rotation induced by aerodynamic thrust. The aerodynamic efficiencies
      for producing both vertical lift and horizontal thrust of the wing are obtained
      using a quasi-steady aerodynamic model and two-dimensional (2D) CFD analysis at
      Reynolds number of 2500. The calculated efficiency data show that both
      efficiencies (propulsive efficiency-etap, and efficiency for producing lift-Pf )
      of the wing are optimized at Strouhal number (St) between 0.1 and 0.5 for a range
      of wing pitch angles (upstroke angle of attack alphau less than 45 degrees ); the
      St for high Pf (St = 0.1 ~ 0.3) is generally lower than for high etap (St = 0.2 ~
      0.5), while the St for equilibrium rotation states lies between the two. Further
      systematic calculations show that the natural equilibrium of the passive rotating
      wing automatically converges to high-efficiency states: above 85% of maximum Pf
      can be obtained for a wide range of prescribed wing kinematics. This study
      provides insight into the aerodynamic efficiency of biological flyers in cruising
      flight, as well as practical applications for micro air vehicle design.

PMID- 29657750
TI  - Anticipation from sensation: using anticipating synchronization to stabilize a
      system with inherent sensory delay.
AB  - We present a novel way of using a dynamical model for predictive tracking control
      that can adapt to a wide range of delays without parameter update. This is
      achieved by incorporating the paradigm of anticipating synchronization (AS),
      where a 'slave' system predicts a 'master' via delayed self-feedback. By treating
      the delayed output of the plant as one half of a 'sensory' AS coupling, the plant
      and an internal dynamical model can be synchronized such that the plant
      consistently leads the target's motion. We use two simulated robotic systems with
      differing arrangements of the plant and internal model ('parallel' and 'serial')
      to demonstrate that this form of control adapts to a wide range of delays without
      requiring the parameters of the controller to be changed.

PMID- 29657751
TI  - Enhancing multi-spot structured illumination microscopy with fluorescence
      difference.
AB  - Structured illumination microscopy is a super-resolution technique used
      extensively in biological research. However, this technique is limited in the
      maximum possible resolution increase. Here we report the results of simulations
      of a novel enhanced multi-spot structured illumination technique. This method
      combines the super-resolution technique of difference microscopy with structured
      illumination deconvolution. Initial results give at minimum a 1.4-fold increase
      in resolution over conventional structured illumination in a low-noise
      environment. This new technique also has the potential to be expanded to further
      enhance axial resolution with three-dimensional difference microscopy. The
      requirement for precise pattern determination in this technique also led to the
      development of a new pattern estimation algorithm which proved more efficient and
      reliable than other methods tested.

PMID- 29657752
TI  - Graphene foam as a biocompatible scaffold for culturing human neurons.
AB  - In this study, we explore the use of electrically active graphene foam as a
      scaffold for the culture of human-derived neurons. Human embryonic stem cell
      (hESC)-derived cortical neurons fated as either glutamatergic or GABAergic
      neuronal phenotypes were cultured on graphene foam. We show that graphene foam is
      biocompatible for the culture of human neurons, capable of supporting cell
      viability and differentiation of hESC-derived cortical neurons. Based on the
      findings, we propose that graphene foam represents a suitable scaffold for
      engineering neuronal tissue and warrants further investigation as a model for
      understanding neuronal maturation, function and circuit formation.

PMID- 29657754
TI  - The effect of ethylene glycol on pore arrangement of anodic aluminium oxide
      prepared by hard anodization.
AB  - The influence of the addition of ethylene glycol (EG) on the pore self-ordering
      process in anodic aluminium oxide (AAO) membranes prepared by hard anodization
      (HA) was investigated. It was illustrated that EG has a substantial effect on the
      pore arrangement of AAO, and it was found that a smaller pore size can be
      obtained with an EG concentration reaching 20 wt% in aqueous electrolyte. The
      number of estimated defects of AAO increases significantly with an increase in EG
      concentration to 50 wt%. Excellent ordering of pores was realized when the
      samples were anodized in the 30 wt%-EG-containing aqueous electrolyte.

PMID- 29657753
TI  - Comparing spatial diversification and meta-population models in the Indo
      Australian Archipelago.
AB  - Reconstructing the processes that have shaped the emergence of biodiversity
      gradients is critical to understand the dynamics of diversification of life on
      Earth. Islands have traditionally been used as model systems to unravel the
      processes shaping biological diversity. MacArthur and Wilson's island
      biogeographic model predicts diversity to be based on dynamic interactions
      between colonization and extinction rates, while treating islands themselves as
      geologically static entities. The current spatial configuration of islands should
      influence meta-population dynamics, but long-term geological changes within
      archipelagos are also expected to have shaped island biodiversity, in part by
      driving diversification. Here, we compare two mechanistic models providing
      inferences on species richness at a biogeographic scale: a mechanistic spatial
      temporal model of species diversification and a spatial meta-population model.
      While the meta-population model operates over a static landscape, the
      diversification model is driven by changes in the size and spatial configuration
      of islands through time. We compare the inferences of both models to floristic
      diversity patterns among land patches of the Indo-Australian Archipelago.
      Simulation results from the diversification model better matched observed
      diversity than a meta-population model constrained only by the contemporary
      landscape. The diversification model suggests that the dynamic re-positioning of
      islands promoting land disconnection and reconnection induced an accumulation of
      particularly high species diversity on Borneo, which is central within the island
      network. By contrast, the meta-population model predicts a higher diversity on
      the mainlands, which is less compatible with empirical data. Our analyses
      highlight that, by comparing models with contrasting assumptions, we can pinpoint
      the processes that are most compatible with extant biodiversity patterns.

PMID- 29657755
TI  - Landslides and dam damage resulting from the Jiuzhaigou earthquake (8 August
      2017), Sichuan, China.
AB  - At 21.19 on 8 August 2017, an Ms 7.0 earthquake struck the Jiuzhaigou scenic spot
      in northwestern Sichuan Province, China. The Jiuzhaigou earthquake is a strike
      slip earthquake with a focal depth of 20 km at 33.20 degrees  N and 103.82
      degrees  E, and was caused by two concealed faults. According to emergency
      investigations and remote sensing interpretations, the Jiuzhaigou earthquake
      triggered 1780 landslides, damaged one dam (Nuorilang Waterfall) and broke one
      dam (Huohua Lake). The landslides mainly occurred in the Rize Valley and Shuzheng
      Valley and in Jiuzhai Paradise. The landslides involved hanging wall and back
      slope effects, and the slope angle, slope aspect, seismic faults and valley trend
      were obviously related to the occurrence of the landslides. Specifically, most of
      the landslides were shallow landslides, rockfalls and rock avalanches and were
      small in scale. The failure modes of landslides mainly include wedge rock mass
      failure, residual deposit failure, relaxed rock mass failure and weathered rock
      mass failure. The initial low stability of the dam coupled with the topographic
      effect, back-slope effect and excess pore water pressure led to damage to the
      Nuorilang Waterfall dam.

PMID- 29657756
TI  - Synthesis of novel and stable g-C3N4-Bi2WO6 hybrid nanocomposites and their
      enhanced photocatalytic activity under visible light irradiation.
AB  - Graphitic carbon nitride (g-C3N4) nanosheets with a thickness of only a few
      nanometres were obtained by a facile deammoniation treatment of bulk g-C3N4 and
      were further hybridized with Bi2WO6 nanoparticles on the surface via a
      solvothermal method. The composite photocatalysts were characterized by powder X
      ray diffraction, scanning electron microscopy, transmission electron microscopy,
      UV-vis diffuse reflection spectroscopy and X-ray photoelectron spectroscopy
      (XPS). The HR-TEM results show that the nano-sized Bi2WO6 particles were finely
      distributed on g-C3N4 sheet surface, which forms heterojunction structure. The UV
      vis diffuse reflectance spectra (DRS) show that the absorption edge of composite
      photocatalysts shifts towards lower energy region in comparison with those of
      pure g-C3N4 and Bi2WO6. The degradation of methyl orange (MO) tests reveals that
      the optimum activity of 8 : 2 g-C3N4-Bi2WO6 photocatalyst is almost 2.7 and 8.5
      times higher than those of individual g-C3N4 and Bi2WO6. Moreover, the recycle
      experiments depict high stability of the composite photocatalysts. Through the
      study of the influencing factors, a possible photocatalytic mechanism is
      proposed. The enhancement in both photocatalytic performance and stability was
      caused by the synergistic effect, including the effective separation of the
      photogenerated electron-hole pairs at the interface of g-C3N4 and Bi2WO6, the
      smaller the particle size and the relatively larger specific surface area of the
      composite photocatalyst.

PMID- 29657757
TI  - Investigation on preferably oriented abnormal growth of CdSe nanorods along
      (0002) plane synthesized by henna leaf extract-mediated green synthesis.
AB  - The theme of this work is to highlight the significance of green plant extracts
      in the synthesis of nanostructures. In asserting this statement, herein, we
      report our obtained results on the synthesis of hexagonal CdSe nanorods
      preferably oriented along (0002) plane through henna leaf extract-mediated
      reaction along with a discussion about the structural, morphological and optical
      properties of the synthesized nanorods. The possible mechanism for the synthesis
      of CdSe nanorods was explored. The formation of nanorods along (0002) plane was
      confirmed by the relatively high intensity of the (0002) peak in X-ray
      diffraction pattern. To account for the experimentally realistic condition, we
      have calculated the surface energies of hexagonal CdSe surface slabs along the
      low indexed (0002), [Formula: see text] and [Formula: see text] plane surfaces
      using density functional theory approach and the calculated surface energy value
      for (0002) surface is 802.7 mJ m-2, which is higher than [Formula: see text] and
      [Formula: see text] surfaces. On realizing the calculated surface energies of
      these slabs, we determined that the combination of [Formula: see text] and
      [Formula: see text] planes with lower surface energies will lead to the formation
      of CdSe nanorods growth along (0002) orientation. Finally, we argue that the
      design of new greener route for the synthesis of novel functional nanomaterials
      is highly desired.

PMID- 29657758
TI  - Temporal and spatial changes in wall shear stress during atherosclerotic plaque
      progression in mice.
AB  - Wall shear stress (WSS) is involved in atherosclerotic plaque initiation, yet its
      role in plaque progression remains unclear. We aimed to study (i) the temporal
      and spatial changes in WSS over a growing plaque and (ii) the correlation between
      WSS and plaque composition, using animal-specific data in an atherosclerotic
      mouse model. Tapered casts were placed around the right common carotid arteries
      (RCCA) of ApoE-/- mice. At 5, 7 and 9 weeks after cast placement, RCCA geometry
      was reconstructed using contrast-enhanced micro-CT. Lumen narrowing was observed
      in all mice, indicating the progression of a lumen intruding plaque. Next, we
      determined the flow rate in the RCCA of each mouse using Doppler Ultrasound and
      computed WSS at all time points. Over time, as the plaque developed and further
      intruded into the lumen, absolute WSS significantly decreased. Finally at week 9,
      plaque composition was histologically characterized. The proximal part of the
      plaque was small and eccentric, exposed to relatively lower WSS. Close to the
      cast a larger and concentric plaque was present, exposed to relatively higher
      WSS. Lower WSS was significantly correlated to the accumulation of macrophages in
      the eccentric plaque. When pooling data of all animals, correlation between WSS
      and plaque composition was weak and no longer statistically significant. In
      conclusion, our data showed that in our mouse model absolute WSS strikingly
      decreased during disease progression, which was significantly correlated to
      plaque area and macrophage content. Besides, our study demonstrates the necessity
      to analyse individual animals and plaques when studying correlations between WSS
      and plaque composition.

PMID- 29657759
TI  - Colorimetric detection of hydrogen peroxide by dioxido-vanadium(V) complex
      containing hydrazone ligand: synthesis and crystal structure.
AB  - Dioxido-vanadium(V) complex has been synthesized in good yield, the complex was
      characterized by IR, UV-visible and 1H NMR spectroscopy. Single crystal X-ray
      crystallography techniques were used to assign the structure of the complex.
      Complex crystallized with monoclinic P21/c space group with cell parameters a (A)
      = 39.516(5), b (A) = 6.2571(11), c (A) = 17.424(2), alpha ( degrees ) = 90, beta
      ( degrees ) = 102.668(12) and gamma ( degrees ) = 90. The hydrazone ligand is
      coordinate to metal ion in tridentate fashion through -ONO- donor atoms forming a
      distorted square pyramidal geometry around the metal ion.

PMID- 29657760
TI  - Pseudo-enantiomeric chiral components and formation of the helical micro- and
      nanostructures in charge-transfer complexes.
AB  - Helical organic micro- and nanostructures are formed by a charge-transfer
      complex, cinchonidine-TCNQ. These unusual forms result from the chirality, the
      steric structure and specific interactions of cinchonidine molecules. These
      materials are semiconductors (10-4 S cm-1), with the typical absorption spectra
      in IR and UV-vis, but also have a characteristic of CD spectrum. Surprisingly,
      conductive micro and nano helices are not formed in pseudo-enantiomeric
      cinchonine, i.e. the complex of cinchonine and TCNQ.

PMID- 29657761
TI  - A Bayesian phylogenetic study of the Dravidian language family.
AB  - The Dravidian language family consists of about 80 varieties (Hammarstrom H. 2016
      Glottolog 2.7) spoken by 220 million people across southern and central India and
      surrounding countries (Steever SB. 1998 In The Dravidian languages (ed. SB
      Steever), pp. 1-39: 1). Neither the geographical origin of the Dravidian language
      homeland nor its exact dispersal through time are known. The history of these
      languages is crucial for understanding prehistory in Eurasia, because despite
      their current restricted range, these languages played a significant role in
      influencing other language groups including Indo-Aryan (Indo-European) and Munda
      (Austroasiatic) speakers. Here, we report the results of a Bayesian phylogenetic
      analysis of cognate-coded lexical data, elicited first hand from native speakers,
      to investigate the subgrouping of the Dravidian language family, and provide
      dates for the major points of diversification. Our results indicate that the
      Dravidian language family is approximately 4500 years old, a finding that
      corresponds well with earlier linguistic and archaeological studies. The main
      branches of the Dravidian language family (North, Central, South I, South II) are
      recovered, although the placement of languages within these main branches
      diverges from previous classifications. We find considerable uncertainty with
      regard to the relationships between the main branches.

PMID- 29657762
TI  - Bayesian model evidence as a practical alternative to deviance information
      criterion.
AB  - While model evidence is considered by Bayesian statisticians as a gold standard
      for model selection (the ratio in model evidence between two models giving the
      Bayes factor), its calculation is often viewed as too computationally demanding
      for many applications. By contrast, the widely used deviance information
      criterion (DIC), a different measure that balances model accuracy against
      complexity, is commonly considered a much faster alternative. However, recent
      advances in computational tools for efficient multi-temperature Markov chain
      Monte Carlo algorithms, such as steppingstone sampling (SS) and thermodynamic
      integration schemes, enable efficient calculation of the Bayesian model evidence.
      This paper compares both the capability (i.e. ability to select the true model)
      and speed (i.e. CPU time to achieve a given accuracy) of DIC with model evidence
      calculated using SS. Three important model classes are considered: linear
      regression models, mixed models and compartmental models widely used in
      epidemiology. While DIC was found to correctly identify the true model when
      applied to linear regression models, it led to incorrect model choice in the
      other two cases. On the other hand, model evidence led to correct model choice in
      all cases considered. Importantly, and perhaps surprisingly, DIC and model
      evidence were found to run at similar computational speeds, a result reinforced
      by analytically derived expressions.

PMID- 29657763
TI  - Synthesis and characterization of dextran-coated iron oxide nanoparticles.
AB  - Synthesis and characterization of iron oxide nanoparticles coated with a large
      molar weight dextran for environmental applications are reported. The first
      experiments involved the synthesis of iron oxide nanoparticles which were coated
      with dextran at different concentrations. The synthesis was performed by a co
      precipitation technique, while the coating of iron oxide nanoparticles was
      carried out in solution. The obtained nanoparticles were characterized by using
      scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray
      diffraction spectrometry, Fourier transform infrared spectroscopy and
      superconducting quantum interference device magnetometry. The results
      demonstrated a successful coating of iron oxide nanoparticles with large molar
      weight dextran, of which agglomeration tendency depended on the amount of dextran
      in the coating solution. SEM and TEM observations have shown that the iron oxide
      nanoparticles are of about 7 nm in size.

PMID- 29657764
TI  - Effects of elevated carbon dioxide on male and female behavioural lateralization
      in a temperate goby.
AB  - Behavioural abnormality in fishes has been proposed as a significant consequence
      of the increasing levels of carbon dioxide occurring in the oceans. Negative
      effects of elevated CO2 have been reported for behaviours such as predator-prey
      interactions, foraging, hearing and behavioural lateralization. Importantly, the
      effects vary greatly both within and between species, and some recent studies
      have shown minimal effects of CO2 on behaviour. Whether the effect of CO2 also
      varies between males and females is, however, virtually unexplored. According to
      resource allocation theory, females are expected to be more sensitive to elevated
      CO2, meaning that non-sex-specific studies may overlook ecologically important
      differences between the sexes. In this study, we investigated the possible
      differences between males and females in their response to elevated CO2 by
      performing behavioural lateralization tests in adult temperate two-spotted
      gobies, Gobiusculus flavescens. We found that the strength of the side bias
      (absolute lateralization) was unaffected by the CO2 treatment, and there was no
      difference between males and females. The control fish were slightly right-biased
      in their behavioural asymmetry (mean relative lateralization of 14). Exposure to
      high CO2 affected this pattern, such that treated fish were slightly left-biased
      (mean relative lateralization of -10), regardless of their sex. The same results
      were obtained yet again when the study was repeated during a second year. We
      discuss our results in light of the great variation in lateralization that has
      been reported to depend on variables such as species, ecological settings and
      environmental factors.

PMID- 29657765
TI  - Raptor migration in an oceanic flyway: wind and geography shape the migratory
      route of grey-faced buzzards in East Asia.
AB  - Flapping flight is relatively costly for soaring birds such as raptors. To avoid
      costly flight, migrating raptors generally avoid flying over water. As a result,
      all but one of the global raptor migration flyways are largely over land. The
      East Asian oceanic flyway for raptors is the exception. Raptor species using this
      flyway migrate by island-hopping, flying over open ocean for distances of up to
      300 km between islands. We used satellite telemetry data for grey-faced buzzards
      Butastur indicus, a species that dominates the southern part of the flyway, to
      investigate the geographical and atmospheric factors responsible for the
      suitability of this flyway for raptor migration. Using a combination of least
      cost path analysis and a step selection function, we found that the occurrence of
      numerous islands and also suitable wind support along the oceanic flyway are
      responsible for route selection in grey-faced buzzards. These results confirm the
      role of islands, but also wind, in shaping the East Asian oceanic flyway of long
      distance raptor migration.

PMID- 29657766
TI  - Mechanical characteristics of beta sheet-forming peptide hydrogels are dependent
      on peptide sequence, concentration and buffer composition.
AB  - Self-assembling peptide hydrogels can be modified regarding their
      biodegradability, their chemical and mechanical properties and their
      nanofibrillar structure. Thus, self-assembling peptide hydrogels might be
      suitable scaffolds for regenerative therapies and tissue engineering. Owing to
      the use of various peptide concentrations and buffer compositions, the self
      assembling peptide hydrogels might be influenced regarding their mechanical
      characteristics. Therefore, the mechanical properties and stability of a set of
      self-assembling peptide hydrogels, consisting of 11 amino acids, made from four
      beta sheet self-assembling peptides in various peptide concentrations and buffer
      compositions were studied. The formed self-assembling peptide hydrogels exhibited
      stiffnesses ranging from 0.6 to 205 kPa. The hydrogel stiffness was mostly
      affected by peptide sequence followed by peptide concentration and buffer
      composition. All self-assembling peptide hydrogels examined provided a
      nanofibrillar network formation. A maximum self-assembling peptide hydrogel
      dissolution of 20% was observed for different buffer solutions after 7 days. The
      stability regarding enzymatic and bacterial digestion showed less degradation in
      comparison to the self-assembling peptide hydrogel dissolution rate in buffer.
      The tested set of self-assembling peptide hydrogels were able to form stable
      scaffolds and provided a broad spectrum of tissue-specific stiffnesses that are
      suitable for a regenerative therapy.

PMID- 29657767
TI  - Graph analysis of cell clusters forming vascular networks.
AB  - This manuscript describes the experimental observation of vasculogenesis in chick
      embryos by means of network analysis. The formation of the vascular network was
      observed in the area opaca of embryos from 40 to 55 h of development. In the area
      opaca endothelial cell clusters self-organize as a primitive and approximately
      regular network of capillaries. The process was observed by bright-field
      microscopy in control embryos and in embryos treated with Bevacizumab
      (Avastin(r)), an antibody that inhibits the signalling of the vascular
      endothelial growth factor (VEGF). The sequence of images of the vascular growth
      were thresholded, and used to quantify the forming network in control and Avastin
      treated embryos. This characterization is made by measuring vessels density,
      number of cell clusters and the largest cluster density. From the original
      images, the topology of the vascular network was extracted and characterized by
      means of the usual network metrics such as: the degree distribution, average
      clustering coefficient, average short path length and assortativity, among
      others. This analysis allows to monitor how the largest connected cluster of the
      vascular network evolves in time and provides with quantitative evidence of the
      disruptive effects that Avastin has on the tree structure of vascular networks.

PMID- 29657768
TI  - Water-mediated green synthesis of PbS quantum dot and its glutathione and biotin
      conjugates for non-invasive live cell imaging.
AB  - This study addresses the cellular uptake of nanomaterials in the field of bio
      applications. In the present study, we have synthesized water-soluble lead
      sulfide quantum dot (PbS QD) with glutathione and 3-MPA (mercaptopropionic acid)
      as the stabilizing ligand using a green approach. 3-MPA-capped QDs were further
      modified with streptavidin and then bound to biotin because of its high
      conjugation efficiency. Labelling and bio-imaging of cells with these bio
      conjugated QDs were evaluated. The bright red fluorescence from these types of
      QDs in HeLa cells makes these materials suitable for deep tissue imaging.

PMID- 29657769
TI  - Simplified models of the symmetric single-pass parallel-plate counterflow heat
      exchanger: a tutorial.
AB  - The heat exchanger is important in practical thermal processes, especially those
      of (i) the molten-salt storage schemes, (ii) compressed air energy storage
      schemes and (iii) other load-shifting thermal storage presumed to undergird a
      Smart Grid. Such devices, although central to the utilization of energy from
      sustainable (but intermittent) renewable sources, will be unfamiliar to many
      scientists, who nevertheless need a working knowledge of them. This tutorial
      paper provides a largely self-contained conceptual introduction for such persons.
      It begins by modelling a novel quantized exchanger, impractical as a device, but
      useful for comprehending the underlying thermophysics. It then reviews the one
      dimensional steady-state idealization which demonstrates that effectiveness of
      heat transfer increases monotonically with (device length)/(device throughput).
      Next, it presents a two-dimensional steady-state idealization for plug flow and
      from it derives a novel formula for effectiveness of transfer; this formula is
      then shown to agree well with a finite-difference time-domain solution of the two
      dimensional idealization under Hagen-Poiseuille flow. These results are
      consistent with a conclusion that effectiveness of heat exchange can approach
      unity, but may involve unwelcome trade-offs among device cost, size and
      throughput.

PMID- 29657770
TI  - Structural characterization of alkali-soluble polysaccharides from Panax ginseng
      C. A. Meyer.
AB  - Panax ginseng C. A. Meyer (ginseng) has been widely used as a herb and functional
      food in the world. Polysaccharides are the main active components of ginseng. In
      this paper, the polysaccharides were sequentially extracted by 50 mM Na2CO3, 1 M
      KOH and 4 M KOH from ginseng roots treated sequentially with hot water, alpha
      amylase and ethylenediaminetetraacetic acid extraction. Na2CO3-soluble ginseng
      polysaccharide (NGP) was fractionated into one neutral and three acidic fractions
      by anion exchange and gel permeation chromatography. Fourier transform infrared,
      NMR and methylation analysis indicated acidic fractions in NGP were highly
      branched rhamnogalacturonan-I domains, with  -> 4)-alpha-GalpA-(1 -> 2)-alpha
      Rhap-(1 -> disaccharide repeating units as backbone and beta-1,4-galactan, alpha
      1,5/1,3,5-arabinan and type II arabinogalactan as side chains. 1-KGP (1 M KOH
      soluble ginseng polysaccharide) and 4-KGP (4 M KOH-soluble ginseng
      polysaccharide) were mainly composed of hemicellulose besides starch-like
      polysaccharides and minor pectin. Antibody detection, enzymic hydrolysis, high
      performance anion exchange chromatography and methylation analysis demonstrated
      xylan was the major component in 1-KGP, while xyloglucan was predominant in 4
      KGP. Comparing the polysaccharides obtained by different solvent extractions, we
      have a comprehensive understanding about total ginseng polysaccharides.

PMID- 29657771
TI  - Taphonomy of Isisfordia duncani specimens from the Lower Cretaceous (upper
      Albian) portion of the Winton Formation, Isisford, central-west Queensland.
AB  - Taphonomic analysis of fossil material can benefit from including the results of
      actualistic decay experiments. This is crucial in determining the autochthony or
      allochthony of fossils of juvenile and adult Isisfordia duncani, a basal
      eusuchian from the Lower Cretaceous (upper Albian) distal-fluvial-deltaic lower
      Winton Formation near Isisford. The taphonomic characteristics of the I. duncani
      fossils were documented using a combination of traditional taphonomic analysis
      alongside already published actualistic decay data from juvenile Crocodylus
      porosus carcasses. We found that the I. duncani holotype, paratypes and referred
      specimens show little signs of weathering and no signs of abrasion.
      Disarticulated skeletal elements are often found in close proximity to the rest
      of the otherwise articulated skeleton. The isolated and disarticulated skeletal
      elements identified, commonly cranial, maxillary and mandibular elements, are
      typical of lag deposits. The holotype QM F36211 and paratype QM F34642 were
      classified as autochthonous, and the remaining I. duncani paratypes and referred
      specimens are parautochthonous. We propose that I. duncani inhabited upper and
      lower delta plains near the Eromanga Sea in life. Their carcasses were buried in
      sediment-laden floodwaters in delta plain overbank and distributary channel
      deposits. Future studies should refer to I. duncani as a brackish water tolerant
      species.

PMID- 29657772
TI  - pH-responsive polymeric micelles self-assembled from amphiphilic copolymer
      modified with lipid used as doxorubicin delivery carriers.
AB  - In the present study, a novel pH-responsive amphiphilic copolymer, 1,2-distearoyl
      sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)] conjugated
      poly(beta-amino esters) (DSPE-b-PEG-b-PAE-b-PEG-b-DSPE), was designed and
      successfully synthesized via Michael-type step polymerization. The chemical
      structure of the pentablock copolymer was confirmed with proton nuclear magnetic
      resonance (1H-NMR) and Fourier transform infrared (FT-IR) spectroscopy. The
      copolymer was able to self-assemble into core/shell polymeric micelles in aqueous
      solution at low concentrations, and its critical micelle concentration (CMC)
      value was 4.5 mg l-1 determined by fluorescence spectrophotometry. The pKb value
      of the copolymer was about 6.5, confirmed by acid-base titration, indicating the
      pH-sensitivity of the polymeric micelle. The hydrodynamic diameter, distribution
      and zeta potential of the polymeric micelles at different pH conditions were
      monitored by dynamic light scattering (DLS). Doxorubicin (DOX) was encapsulated
      into the core of the micelles with a high drug loading content (15.9%) and
      entrapment efficacy (60.4%). In vitro experiments demonstrated that the release
      behaviour of DOX from the DOX-loaded polymeric micelles (DOX-PMs) was pH
      triggered. When the pH decreased from 7.4 to 5.0, the drug release rate was
      markedly accelerated. MTT assay showed that the copolymer had negligible
      cytotoxicity whereas the DOX-PMs displayed high toxicity for tumour cells such as
      B16F10, HepG2 and HeLa cell lines. The results demonstrated that these pH
      sensitive polymeric micelles could be used as potential anti-cancer drug carriers
      for cancer chemotherapy with controlled release.

PMID- 29657773
TI  - Preparation, characterization and luminescence properties of core-shell ternary
      terbium composites SiO2(600)@Tb(MABA-Si)*L.
AB  - Two novel core-shell structure ternary terbium composites SiO2(600)@Tb(MABA
      Si).L(L:dipy/phen) nanometre luminescence materials were prepared by ternary
      terbium complexes Tb(MABA-Si).L2.(ClO4)3.2H2O shell grafted onto the surface of
      SiO2 microspheres. And corresponding ternary terbium complexes were synthesized
      using (CONH(CH2)3Si(OCH2CH3)3)2 (denoted as MABA-Si) as first ligand and L as
      second ligand coordinated with terbium perchlorate. The as-synthesized products
      were characterized by means of IR spectra, 1HNMR, element analysis, molar
      conductivity, SEM and TEM. It was found that the first ligand MABA-Si of terbium
      ternary complex hydrolysed to generate the Si-OH and the Si-OH condensate with
      the Si-OH on the surface of SiO2 microspheres; then ligand MABA-Si grafted onto
      the surface of SiO2 microspheres. The diameter of SiO2 core of SiO2(600)@Tb(MABA
      Si).L was approximately 600 nm. Interestingly, the luminescence properties
      demonstrate that the two core-shell structure ternary terbium composites
      SiO2(600)Tb(MABA-Si).L(dipy/phen) exhibit strong emission intensities, which are
      2.49 and 3.35 times higher than that of the corresponding complexes Tb(MABA
      Si).L2.(ClO4)3.2H2O, respectively. Luminescence decay curves show that core-shell
      structure ternary terbium composites have longer lifetime. Excellent luminescence
      properties enable the core-shell materials to have potential applications in
      medicine, industry, luminescent fibres and various biomaterials fields.

PMID- 29657774
TI  - A mathematical model of marine bacteriophage evolution.
AB  - To explore how particularities of a host cell-virus system, and in particular
      host cell replication, affect viral evolution, in this paper we formulate a
      mathematical model of marine bacteriophage evolution. The intrinsic simplicity of
      real-life phage-bacteria systems, and in particular aquatic systems, for which
      the assumption of homogeneous mixing is well justified, allows for a reasonably
      simple model. The model constructed in this paper is based upon the Beretta-Kuang
      model of bacteria-phage interaction in an aquatic environment (Beretta & Kuang
      1998 Math. Biosci.149, 57-76. (doi:10.1016/S0025-5564(97)10015-3)). Compared to
      the original Beretta-Kuang model, the model assumes the existence of a multitude
      of viral variants which correspond to continuously distributed phenotypes. It is
      noteworthy that the model is mechanistic (at least as far as the Beretta-Kuang
      model is mechanistic). Moreover, this model does not include any explicit law or
      mechanism of evolution; instead it is assumed, in agreement with the principles
      of Darwinian evolution, that evolution in this system can occur as a result of
      random mutations and natural selection. Simulations with a simplistic linear
      fitness landscape (which is chosen for the convenience of demonstration only and
      is not related to any real-life system) show that a pulse-type travelling wave
      moving towards increasing Darwinian fitness appears in the phenotype space. This
      implies that the overall fitness of a viral quasi-species steadily increases with
      time. That is, the simulations demonstrate that for an uneven fitness landscape
      random mutations combined with a mechanism of natural selection (for this
      particular system this is given by the conspecific competition for the resource)
      lead to the Darwinian evolution. It is noteworthy that in this system the speed
      of propagation of this wave (and hence the rate of evolution) is not constant but
      varies, depending on the current viral fitness and the abundance of susceptible
      bacteria. A specific feature of the original Beretta-Kuang model is that this
      model exhibits a supercritical Hopf bifurcation, leading to the loss of stability
      and the rise of self-sustained oscillations in the system. This phenomenon
      corresponds to the paradox of enrichment in the system. It is remarkable that
      under the conditions that ensure the bifurcation in the Beretta-Kuang model, the
      viral evolution model formulated in this paper also exhibits a rise in self
      sustained oscillations of the abundance of all interacting populations. The
      propagation of the travelling wave, however, remains stable under these
      conditions. The only visible impact of the oscillations on viral evolution is a
      lower speed of the evolution.

PMID- 29657775
TI  - Nanostructured polyurethane perylene bisimide ester assemblies with tuneable
      morphology and enhanced stability.
AB  - Size control has been successfully achieved in inorganic materials, but it
      remains a challenge in polymer nanomaterials due to their polydispersity. Here,
      we report a facile approach to tailor the diameters of polyurethane (PU)
      nanoparticles (490 nm, 820 nm and 2.1 um) via perylene bisimide (PBI) assisted
      self-assembly. The formed morphologies such as spindle, spherical and core-shell
      structures depend on the ratio of PBI and polymer concentrations. It is shown
      that the formation of PU nanoparticles is directed by pi-pi stacking of PBI and
      the morphology transition is not only affected by the amount of PBI incorporated,
      but also influenced by solvent, which controls the initial evaporation balance.
      Furthermore, the prepared PUs exhibit retained optical stability and enhanced
      thermal stability. The PUs, designed to have conjugated PBI segments in
      backbones, were synthesized via ring-opening and condensation reactions. Compared
      with the neat PU, gel permeation chromatography shows narrower molecular weight
      distribution. Fluorescence spectra and ultraviolet-visible spectra indicate
      retained maximum emission wavelength of PBI at 574 nm and 5.2% quantum yields.
      Thermo-gravimetric analysis and differential scanning calorimetry reveal 79
      degrees C higher decomposition temperature and 22 degrees C higher glass
      transition temperature. This study provides a new way to fabricate well-defined
      nanostructures of functionalized PUs.

PMID- 29657776
TI  - Incorporation of Mn2+ into CdSe quantum dots by chemical bath co-deposition
      method for photovoltaic enhancement of quantum dot-sensitized solar cells.
AB  - A photoelectric conversion efficiency (PCE) of 4.9% was obtained under 100 mW cm
      2 illumination by quantum-dot-sensitized solar cells (QDSSCs) using a CdS/Mn :
      CdSe sensitizer. CdS quantum dots (QDs) were deposited on a TiO2 mesoporous oxide
      film by successive ionic layer absorption and reaction. Mn2+ doping into CdSe QDs
      is an innovative and simple method-chemical bath co-deposition, that is, mixing
      the Mn ion source with CdSe precursor solution for Mn : CdSe QD deposition.
      Compared with the CdS/CdSe sensitizer without Mn2+ incorporation, the PCE was
      increased from 3.4% to 4.9%. The effects of Mn2+ doping on the chemical, physical
      and photovoltaic properties of the QDSSCs were investigated by energy dispersive
      spectrometry, absorption spectroscopy, photocurrent density-voltage
      characteristics and electrochemical impedance spectroscopy. Mn-doped CdSe QDs in
      QDSSCs can obtain superior light absorption, faster electron transport and slower
      charge recombination than CdSe QDs.

PMID- 29657777
TI  - The preparation of Fe2O3-ZSM-5 catalysts by metal-organic chemical vapour
      deposition method for catalytic wet peroxide oxidation of m-cresol.
AB  - Fe2O3-ZSM-5 catalysts (0.6 wt% Fe load) prepared by metal-organic chemical vapour
      deposition (MOCVD) method were evaluated in the catalytic wet peroxide oxidation
      (CWPO) of m-cresol in a batch reactor. The catalysts have a good iron dispersion
      and small iron crystalline size, and exhibit high stability during reaction. In
      addition, the kinetics of the reaction were studied and the initial oxidation
      rate equation was given. Catalysts were first characterized by N2 adsorption
      desorption isotherms, scanning electronic microscopy, energy-dispersive
      spectroscopy, X-ray diffraction and X-ray photoelectron spectroscopy. Results
      show that extra-framework Fe3+ species (presenting in the form of Fe2O3) are
      successfully loaded on ZSM-5 supports by MOCVD method. Performances of catalysts
      were tested and effects of different temperature, stirring rate, catalyst amount
      on hydrogen peroxide, m-cresol, total organic carbon (TOC) conversion and Fe
      leaching concentration were studied. Results reveal that catalytic activity
      increased with higher temperature, faster stirring rate and larger catalyst
      amount. In all circumstances, m-cresol conversion could reach 99% in 0.5-2.5 h,
      and the highest TOC removal (80.5%) is obtained after 3 h under conditions of 60
      degrees C, 400 r.p.m. and catalyst amount of 2.5 g l-1. The iron-leaching
      concentrations are less than 1.1 mg l-1 under all conditions. The initial
      oxidation rate equation [Formula: see text] is obtained for m-cresol degradation
      with Fe2O3-ZSM-5 catalysts.

PMID- 29657778
TI  - Adopted daughters and adopted daughters-in-law in Taiwan: a mortality analysis.
AB  - Adoption is sometimes considered paradoxical from an evolutionary perspective
      because the costs spent supporting an adopted child would be better spent on
      rearing one's own. Kin selection theory is commonly used to solve this paradox,
      because the adoption of closely related kin contributes to the inclusive fitness
      of the adoptive parent. In this paper, we perform a novel test of kin selection
      theory in the context of adoption by asking whether adopted daughters-in-law, who
      contribute directly (i.e. genealogically) to the perpetuation of their adoptive
      families' lineages, experience lower mortality than daughters adopted for other
      purposes in historical Taiwan. We show that both classes of adopted daughter
      suffer lower mortality than biological daughters, but that the protective effect
      of adoption is stronger among daughters who were not adopted with the intention
      of perpetuating the family lineage. We speculate as to the possible benefits of
      such a pattern and emphasize the need to move beyond typological definitions of
      adoption to understand the specific costs and benefits involved in different
      forms of caring for others' children.

PMID- 29657779
TI  - Cleaner fish escape salmon farms and hybridize with local wrasse populations.
AB  - The genetic impact of farmed fish escaping aquaculture is a highly debated issue.
      However, non-target species, such as cleaner fish used to remove sea lice from
      farmed fish, are rarely considered. Here, we report that wild corkwing wrasse
      (Symphodus melops), which are transported long distances to be used as cleaner
      fish in salmon farms, escape and hybridize with local populations. Recently,
      increasing numbers of corkwing wrasse have been reported in Flatanger in Norway,
      north of its described distribution range, an area heavily relying on the import
      of cleaner fish from Skagerrak. Using genetic markers identified with 2bRAD
      sequencing, we show that, although the Flatanger population largely is a result
      of a northward range expansion, there is also evidence of considerable gene flow
      from southern populations in Skagerrak and Kattegat. Of the 40 corkwing wrasses
      sampled in Flatanger, we discovered two individuals with clear southern
      genotypes, one first-generation hybrid, and 12 potential second-generation
      hybrids. In summary, we provide evidence that corkwing wrasse escape from fish
      farms and hybridize with local populations at the leading edge of an ongoing
      range expansion. Although the magnitude and significance of escapees warrant
      further investigation, these results should be taken into consideration in the
      use of translocated cleaner fish.

PMID- 29657780
TI  - Phylogeny, biogeography and diversification patterns of side-necked turtles
      (Testudines: Pleurodira).
AB  - Pleurodires or side-necked turtles are today restricted to freshwater
      environments of South America, Africa-Madagascar and Australia, but in the past
      they were distributed much more broadly, being found also on Eurasia, India and
      North America, and marine environments. Two hypotheses were proposed to explain
      this distribution; in the first, vicariance would have shaped the current
      geographical distribution and, in the second, extinctions constrained a
      previously widespread distribution. Here, we aim to reconstruct pleurodiran
      biogeographic history and diversification patterns based on a new phylogenetic
      hypothesis recovered from the analysis of the largest morphological dataset yet
      compiled for the lineage, testing which biogeographical process prevailed during
      its evolutionary history. The resulting topology generally agrees with previous
      hypotheses of the group and shows that most diversification shifts were related
      to the exploration of new niches, e.g. littoral or marine radiations. In
      addition, as other turtles, pleurodires do not seem to have been much affected by
      either the Cretaceous-Palaeogene or the Eocene-Oligocene mass extinctions. The
      biogeographic analyses highlight the predominance of both anagenetic and
      cladogenetic dispersal events and support the importance of transoceanic
      dispersals as a more common driver of area changes than previously thought,
      agreeing with previous studies with other non-turtle lineages.

PMID- 29657781
TI  - Comparative limb proportions reveal differential locomotor morphofunctions of
      alligatoroids and crocodyloids.
AB  - Although two major clades of crocodylians (Alligatoroidea and Crocodyloidea) were
      split during the Cretaceous period, relatively few morphological and functional
      differences between them have been known. In addition, interaction of multiple
      morphofunctional systems that differentiated their ecology has barely been
      assessed. In this study, we examined the limb proportions of crocodylians to
      infer the differences of locomotor functions between alligatoroids and
      crocodyloids, and tested the correlation of locomotor and feeding
      morphofunctions. Our analyses revealed crocodyloids including Gavialis have
      longer stylopodia (humerus and femur) than alligatoroids, indicating that two
      groups may differ in locomotor functions. Fossil evidence suggested that
      alligatoroids have retained short stylopodia since the early stage of their
      evolution. Furthermore, rostral shape, an indicator of trophic function, is
      correlated with limb proportions, where slender-snouted piscivorous taxa have
      relatively long stylopodia and short overall limbs. In combination, trophic and
      locomotor functions might differently delimit the ecological opportunity of
      alligatoroids and crocodyloids in the evolution of crocodylians.

PMID- 29657782
TI  - Do an invasive organism's dispersal characteristics affect how we should search
      for it?
AB  - We investigated how an invading organism's dispersal characteristics affect the
      efficacy of different surveillance strategies aimed at detecting that organism as
      it spreads following a new incursion. Specifically, we assessed whether, out of
      the surveillance strategies tested, the best surveillance strategy for an
      organism varied depending on the way it disperses. We simulated the spread of
      invasive organisms with different dispersal characteristics including leptokurtic
      and non-leptokurtic kernels with different median dispersal distances and degrees
      of kurtosis. We evaluated surveillance strategies with different sampling
      arrangements, densities and frequencies. Surveillance outcomes compared included
      the time to detection, the total spread of the invasion and the likelihood of the
      invasion reaching new areas. Overall, dispersal characteristics affected the
      surveillance outcomes, but the grid surveillance arrangement consistently
      performed best in terms of early detection and reduced spread within and between
      fields. Additionally, the results suggest that dispersal characteristics may
      influence spread to new areas and surveillance strategies. Therefore, knowledge
      on an invasive organism's dispersal characteristics may influence how we search
      for it and how we manage the invasion to prevent spread to new areas.

PMID- 29657783
TI  - Research on preparation of phosphate-modified animal glue binder for foundry use.
AB  - In this paper, three phosphates were used as modifiers to modify animal glue
      binder. The structural characteristics and thermal properties of animal glue
      binder treated with phosphates were studied by Fourier transform-infrared
      spectroscopy, gel permeation chromatography and derivative thermogravimetric
      analysis. The results showed that the modified animal glue binder had better sand
      tensile strength and lower viscosity than untreated animal glue binder. The best
      modification process was as follows: the optimal amount of sodium carbonate was 4
      wt% to animal glue; the optimal weight ratio of the modifiers was sodium
      pyrophosphate : sodium tripolyphosphate : sodium hexametaphosphate : animal glue
      = 3 : 3 : 4 : 100, and the optimal reaction should be performed at 80 degrees C
      for a reaction time of 120 min. A final tensile strength of approximately 3.20
      MPa was achieved and the viscosity value was approximately 880 mPa s.

PMID- 29657784
TI  - Kin discrimination via odour in the cooperatively breeding banded mongoose.
AB  - Kin discrimination is often beneficial for group-living animals as it aids in
      inbreeding avoidance and providing nepotistic help. In mammals, the use of
      olfactory cues in kin discrimination is widespread and may occur through learning
      the scents of individuals that are likely to be relatives, or by assessing
      genetic relatedness directly through assessing odour similarity (phenotype
      matching). We use scent presentations to investigate these possibilities in a
      wild population of the banded mongoose Mungos mungo, a cooperative breeder in
      which inbreeding risk is high and females breed communally, disrupting
      behavioural cues to kinship. We find that adults show heightened behavioural
      responses to unfamiliar (extra-group) scents than to familiar (within-group)
      scents. Interestingly, we found that responses to familiar odours, but not
      unfamiliar odours, varied with relatedness. This suggests that banded mongooses
      are either able to use an effective behavioural rule to identify likely relatives
      from within their group, or that phenotype matching is used in the context of
      within-group kin recognition but not extra-group kin recognition. In other
      cooperative breeders, familiarity is used within the group and phenotype matching
      may be used to identify unfamiliar kin. However, for the banded mongoose this
      pattern may be reversed, most likely due to their unusual breeding system which
      disrupts within-group behavioural cues to kinship.

PMID- 29657785
TI  - Spatial variability in size at maturity of golden king crab (Lithodes
      aequispinus) and implications for fisheries management.
AB  - Many crab fisheries around the world are managed by size, sex and season, where
      males are given at least one opportunity to reproduce before being harvested.
      Golden king crab (Lithodes aequispinus) supports a commercial fishery in
      Southeast Alaska and legal size is based on growth and maturity information from
      other parts of their range. Size-at-maturity estimates varied for crabs among
      seven management areas in Southeast Alaska, where male maturity estimates
      increased in size with increases in latitude, while maturity estimates across
      their North Pacific range decreased in size with increases in latitude. Depth,
      temperature and harvest history were not related to variation observed in male
      maturity estimates. Management implications from this research include reducing
      legal size in some areas to maximize harvest potential and increasing in others
      to allow male crabs the opportunity to reproduce before being harvested. A more
      conservative strategy would incorporate the largest maturity estimate, thus
      increasing the legal size which would have a negative impact to the commercial
      fishery, but allow male crabs the opportunity to reproduce before being
      harvested. This study shows the importance of understanding how life-history
      characteristics change over space and the challenge incorporating spatial
      variability for improved fisheries management.

PMID- 29657786
TI  - Amphotericin B-conjugated polypeptide hydrogels as a novel innovative strategy
      for fungal infections.
AB  - The present work is focused on the design and development of novel amphotericin B
      (AmB)-conjugated biocompatible and biodegradable polypeptide hydrogels to improve
      the antifungal activity. Using three kinds of promoting self-assembly groups (2
      naphthalene acetic acid (Nap), naproxen (Npx) and dexamethasone (Dex)) and
      polypeptide sequence (Phe-Phe-Asp-Lys-Tyr, FFDKY), we successfully synthesized
      the Nap-FFDK(AmB)Y gels, Npx-FFDK(AmB)Y gels and Dex-FFDK(AmB)Y gels. The AmB
      conjugated hydrogelators are highly soluble in different aqueous solutions. The
      cryo-transmission electron microscopy and scanning electron microscopy
      micrographs of hydrogels afford nanofibres with a width of 20-50 nm. Powder X-ray
      diffraction analyses demonstrate that the crystalline structures of the AmB and
      Dex are changed into amorphous structures after the formation of hydrogels.
      Circular dichroism spectra of the solution of blank carriers and the
      corresponding drug deliveries further help elucidate the molecular arrangement in
      gel phase, indicating the existence of turn features. The in vitro drug releases
      suggest that the AmB-conjugated hydrogels are suitable as drug-controlled release
      vehicles for hydrophobic drugs. The antifungal effect of AmB-conjugated hydrogels
      significantly exhibits the antifungal activity against Candida albicans. The
      results of the present study indicated that the AmB-conjugated hydrogels are
      suitable carriers for poorly water soluble drugs and for enhancement of
      therapeutic efficacy of antifungal drugs.

PMID- 29657787
TI  - Pressure-induced enhancement in the thermoelectric properties of monolayer and
      bilayer SnSe2.
AB  - The electronic structures of monolayer and bilayer SnSe2 under pressure were
      investigated by using first-principles calculations including van der Waals
      interactions. For monolayer SnSe2, the variation of electronic structure under
      pressure is controlled by pressure-dependent lattice parameters. For bilayer
      SnSe2, the changes in electronic structure under pressure are dominated by
      intralayer and interlayer atomic interactions. The n-type thermoelectric
      properties of monolayer and bilayer SnSe2 under pressure were calculated on the
      basis of the semi-classical Boltzmann transport theory. It was found that the
      electrical conductivity of monolayer and bilayer SnSe2 can be enhanced under
      pressure, and such dependence can be attributed to the pressure-induced changes
      of the Se-Sn antibonding states in conduction band. Finally, the doping
      dependence of power factors of n-type monolayer and bilayer SnSe2 at three
      different pressures were estimated, and the results unveiled that thermoelectric
      performance of n-type monolayer and bilayer SnSe2 can be improved by applying
      external pressure. This study benefits to understand the nature of the transport
      properties for monolayer and bilayer SnSe2 under pressure, and it offers valuable
      insight for designing high-performance thermoelectric few-layered SnSe2 through
      strain engineering induced by external pressure.

PMID- 29657788
TI  - Lepidosaurian diversity in the Mesozoic-Palaeogene: the potential roles of
      sampling biases and environmental drivers.
AB  - Lepidosauria is a speciose clade with a long evolutionary history, but there have
      been few attempts to explore its taxon richness through time. Here we estimate
      patterns of terrestrial lepidosaur genus diversity for the Triassic-Palaeogene
      (252-23 Ma), and compare observed and sampling-corrected richness curves
      generated using Shareholder Quorum Subsampling and classical rarefaction.
      Generalized least-squares regression (GLS) is used to investigate the
      relationships between richness, sampling and environmental proxies. We found low
      levels of richness from the Triassic until the Late Cretaceous (except in the
      Kimmeridgian-Tithonian of Europe). High richness is recovered for the Late
      Cretaceous of North America, which declined across the K-Pg boundary but remained
      relatively high throughout the Palaeogene. Richness decreased following the
      Eocene-Oligocene Grande Coupure in North America and Europe, but remained high in
      North America and very high in Europe compared to the Late Cretaceous; elsewhere
      data are lacking. GLS analyses indicate that sampling biases (particularly, the
      number of fossil collections per interval) are the best explanation for long-term
      face-value genus richness trends. The lepidosaur fossil record presents many
      problems when attempting to reconstruct past diversity, with geographical
      sampling biases being of particular concern, especially in the Southern
      Hemisphere.

PMID- 29657789
TI  - Sensitive colorimetric assay using insulin G-quadruplex aptamer arrays on DNA
      nanotubes coupled with magnetic nanoparticles.
AB  - Described here is a methodology for fabrication of a sensitive colorimetric
      nanoassay for measurement of insulin using G-quadruplex aptamer arrays on DNA
      nanotubes (DNTs) coupled with magnetic nanoparticles. The spectroscopic findings
      (e.g. visible spectra, velocity assay and limit of detection determination)
      indicated a highly sensitive performance of this new nanoassay in comparison to
      those results obtained from the insulin assay with non-arrayed aptamers. The
      clinical performance statistics (i.e. paired sample t-test, Bland-Altman plot and
      scatter diagram) from the newly developed assay and the enzyme-linked
      immunosorbent assay suggested its reliable precision and its acceptable
      repeatability for measurement of insulin in human sera. This is, to our
      knowledge, the first study for the application of magnetic nanoparticle-coupled
      DNTs for carrying G-quadruplex aptamers for detection of biomolecules (such as
      insulin) in human serum.

PMID- 29657790
TI  - Quadrupedal locomotor simulation: producing more realistic gaits using dual
      objective optimization.
AB  - In evolutionary biomechanics it is often considered that gaits should evolve to
      minimize the energetic cost of travelling a given distance. In gait simulation
      this goal often leads to convincing gait generation. However, as the
      musculoskeletal models used get increasingly sophisticated, it becomes apparent
      that such a single goal can lead to extremely unrealistic gait patterns. In this
      paper, we explore the effects of requiring adequate lateral stability and show
      how this increases both energetic cost and the realism of the generated walking
      gait in a high biofidelity chimpanzee musculoskeletal model. We also explore the
      effects of changing the footfall sequences in the simulation so it mimics both
      the diagonal sequence walking gaits that primates typically use and also the
      lateral sequence walking gaits that are much more widespread among mammals. It is
      apparent that adding a lateral stability criterion has an important effect on the
      footfall phase relationship, suggesting that lateral stability may be one of the
      key drivers behind the observed footfall sequences in quadrupedal gaits. The
      observation that single optimization goals are no longer adequate for generating
      gait in current models has important implications for the use of biomimetic
      virtual robots to predict the locomotor patterns in fossil animals.

PMID- 29657791
TI  - Sulfur resistance of Ce-Mn/TiO2 catalysts for low-temperature NH3-SCR.
AB  - Ce-Mn/TiO2 catalyst prepared using a simple impregnation method demonstrated a
      better low-temperature selective catalytic reduction of NO with NH3 (NH3-SCR)
      activity in comparison with the sol-gel method. The Ce-Mn/TiO2 catalyst loading
      with 20% Ce had the best low-temperature activity and achieved a NO conversion
      rate higher than 90% at 140-260 degrees C with a 99.7% NO conversion rate at 180
      degrees C. The Ce-Mn/TiO2 catalyst only had a 6% NO conversion rate decrease
      after 100 ppm of SO2 was added to the stream. When SO2 was removed from the
      stream, the catalyst was able to recover completely. The crystal structure,
      morphology, textural properties and valence state of the metals involving the
      novel catalysts were investigated using X-ray diffraction, N2 adsorption and
      desorption analysis, X-ray photoelectron spectroscopy, scanning electron
      microscopy and energy dispersive spectroscopy, respectively. The decrease of NH3
      SCR performance in the presence of 100 ppm SO2 was due to the decrease of the
      surface area, change of the pore structure, the decrease of Ce4+ and Mn4+
      concentration and the formation of the sulfur phase chemicals which blocked the
      active sites and changed the valence status of the elements.

PMID- 29657792
TI  - Analysis of wild macaque stone tools used to crack oil palm nuts.
AB  - The discovery of oil palm (Elaeis guineensis) nut-cracking by wild long-tailed
      macaques (Macaca fascicularis) is significant for the study of non-human primate
      and hominin percussive behaviour. Up until now, only West African chimpanzees
      (Pan troglodytes verus) and modern human populations were known to use stone
      hammers to crack open this particular hard-shelled palm nut. The addition of non
      habituated, wild macaques increases our comparative dataset of primate lithic
      percussive behaviour focused on this one plant species. Here, we present an
      initial description of hammerstones used by macaques to crack oil palm nuts,
      recovered from active nut-cracking locations on Yao Noi Island, Ao Phang Nga
      National Park, Thailand. We combine a techno-typological approach with
      microscopic and macroscopic use-wear analysis of percussive damage to
      characterize the percussive signature of macaque palm oil nut-cracking tools.
      These artefacts are characterized by a high degree of battering and crushing on
      most surfaces, which is visible at both macro and microscopic levels. The degree
      and extent of this damage is a consequence of a dynamic interplay between a
      number of factors, including anvil morphology and macaque percussive techniques.
      Beyond the behavioural importance of these artefacts, macaque nut-cracking
      represents a new target for primate archaeological investigations, and opens new
      opportunities for comparisons between tool using primate species and with early
      hominin percussive behaviour, for which nut-cracking has been frequently
      inferred.

PMID- 29657793
TI  - Preparation of chitosan/MCM-41-PAA nanocomposites and the adsorption behaviour of
      Hg(II) ions.
AB  - A novel functional hybrid mesoporous composite material (CMP) based on chitosan
      and MCM-41-PAA was reported and its application as an excellent adsorbent for
      Hg(II) ions was also investigated. Innovatively, MCM-41-PAA was prepared by using
      diatomite and polyacrylic acid (PAA) with integrated polymer-silica hybrid
      frameworks, and then CMP was fabricated by introducing MCM-41-PAA to chitosan
      using glutaraldehyde as a cross-linking agent. The structure and morphology of
      CMP were characterized by X-ray diffraction, Fourier transform infrared spectra,
      thermogravimetric analysis, scanning electron microscopy and Brunauer-Emmett
      Teller measurements. The results showed that the CMP possessed multifunctional
      groups such as -OH, -COOH and -NH2 with large specific surface area. Adsorption
      behaviour of Hg(II) ions onto CMP was fitted better by the pseudo-second-order
      kinetic model and the Langmuir model when the initial Hg(II) concentration, pH,
      adsorption temperature and time were 200 mg l-1, 4, 298 K and 120 min,
      respectively, as the optimum conditions. The corresponding maximum adsorption
      capacity could reach 164 mg g-1. According to the thermodynamic parameters
      determined such as free energy, enthalpy and entropy, the adsorption process of
      Hg(II) ions was spontaneous endothermic adsorption.

PMID- 29657794
TI  - Unexpected solvent effects on the UV/Vis absorption spectra of o-cresol in
      toluene and benzene: in contrast with non-aromatic solvents.
AB  - Cresol is a prototype molecule in understanding intermolecular interactions in
      material and biological systems, because it offers different binding sites with
      various solvents and protonation states under different pH values. It is found
      that the UV/Vis absorption spectra of o-cresol in aromatic solvents (benzene,
      toluene) are characterized by a sharp peak, unlike the broad double-peaks in 11
      non-aromatic solvents. Both molecular dynamics simulations and electronic
      structure calculations revealed the formation of intermolecular pi-complexation
      between o-cresol and aromatic solvents. The thermal movements of solvent and
      solute molecules render the conformations of o-cresol changing between trans and
      cis isomers. The pi-interaction makes the cis configuration a dominant isomer,
      hence leading to the single keen-edged UV/Vis absorption peak at approximately
      283 nm. The free conformation changes between trans and cis in aqueous solution
      rationalize the broader absorption peaks in the range of 260-280 nm. The pH
      dependence of the UV/Vis absorption spectra in aqueous solutions is also
      rationalized by different protonation states of o-cresol. The explicit solvent
      model with long-ranged interactions is vital to describe the effects of pi
      complexation and electrostatic interaction on the UV/Vis absorption spectra of o
      cresol in toluene and alkaline aqueous (pH > 10.3) solutions, respectively.

PMID- 29657795
TI  - Adsorption of tetracycline on Fe (hydr)oxides: effects of pH and metal cation
      (Cu2+, Zn2+ and Al3+) addition in various molar ratios.
AB  - Iron (Fe) (hydr)oxides control the mobility and bioavailability of tetracycline
      (TC) in waters and soils. Adsorption of TC on Fe (hydr)oxides is greatly affected
      by polyvalent metals; however, impacts of molar metal/TC ratios on TC adsorptive
      behaviours on Fe (hydr)oxides remain unclear. Results showed that maximum TC
      adsorption on ferrihydrite and goethite occurred at pH 5-6. Such TC adsorption
      was generally promoted by the addition of Cu2+, Zn2+ and Al3+. The greatest
      increase in TC adsorption was found in the system with molar Cu/TC ratio of 3 due
      to the formation of Fe hydr(oxide)-Cu-TC ternary complexes. Functional groups on
      TC that were responsible for the complexation with Cu2+shifted from phenolic
      diketone groups at Cu/TC molar ratio < 1 to amide groups at Cu/TC molar ratio >=
      1. For the addition of Al3+, the complexation only took place with phenolic
      diketone groups, resulting in the enhanced TC adsorption at a molar Al/TC ratio
      of 1. However, TC adsorption decreased for Al/TC molar ratio > 1 as excess Al3+
      led to the competitive adsorption with Al/TC complexes. For the Zn2+ addition, no
      significant correlation was found between TC adsorption capacity and molar Zn/TC
      ratios.

PMID- 29657796
TI  - Synthesis, quantitative structure-property relationship study of novel
      fluorescence active 2-pyrazolines and application.
AB  - A variety of fluorescence-active fluorinated pyrazolines 13-33 was synthesized in
      good yields through cyclocondensation reaction of propenones 1-9 with aryl
      hydrazines 10-12. Some of the synthesized compounds provided promising
      fluorescence properties with quantum yield (Phi) higher than that of quinine
      sulfate (standard reference). Quantitative structure-property relationship
      studies were undertaken supporting the exhibited fluorescence properties and
      estimating the parameters governing properties. Five synthesized fluorescence
      active pyrazolines (13, 15, 18, 19 and 23) with variable Phi were selected for
      treating two types of paper sheets (Fabriano and Bible paper). These investigated
      fluorescence compounds, especially compounds 19 and 23, provide improvements in
      strength properties of paper sheets. Based on the observed performance they can
      be used as markers in security documents.

PMID- 29657797
TI  - Non-invasive paper-based microfluidic device for ultra-low detection of urea
      through enzyme catalysis.
AB  - This work describes the design, fabrication and characterization of a paper-based
      microfluidic device for ultra-low detection of urea through enzyme catalysis. The
      microfluidic system comprises an entry port, a fluidic channel, a reaction zone
      and two electrodes (contacts). Wax printing was used to create fluidic channels
      on the surface of a chromatography paper. Pre-conceptualized designs of the
      fluidic channel are wax-printed on the paper substrate while the electrodes are
      screen-printed. The paper printed with wax is heated to cause the wax reflow
      along the thickness of the paper that selectively creates hydrophilic and
      hydrophobic zones inside the paper. Urease immobilized in the reaction zone
      catalyses urea into releasing ions and, thereby, generating a current flow
      between the electrodes. A measure of current with respect to time at a fixed
      potential enables the detection of urea. The methodology enabled urea
      concentration down to 1 pM to be detected. The significance of this work lies in
      the use of simple and inexpensive paper-based substrates to achieve detection of
      ultra-low concentrations of analytes such as urea. The process is non-invasive
      and employs a less cumbersome two-electrode assembly.

PMID- 29657798
TI  - The importance of sampling standardization for comparisons of insect herbivory in
      deep time: a case study from the late Palaeozoic.
AB  - Sampling standardization has not been fully addressed for the study of insect
      herbivory in the fossil record. The effects of sampling within a single locality
      were explored almost a decade ago, but the importance of sampling standardization
      for comparisons of herbivory across space and time has not yet been evaluated.
      Here, we present a case study from the Permian in which we evaluate the impact of
      sampling standardization on comparisons of insect herbivory from two localities
      that are similar in age and floral composition. Comparisons of insect damage type
      (DT) diversity change dramatically when the number of leaves examined is
      standardized by surface area. This finding suggests that surface area should
      always be taken into account for comparisons of DT diversity. In addition, the
      three most common metrics of herbivory-DT diversity, proportion of leaves
      herbivorized and proportion of leaf surface area herbivorized-are inherently
      decoupled from each other. The decoupling of the diversity and intensity of
      insect herbivory necessitates a reinterpretation of published data because they
      had been conflated in previous studies. Future studies should examine the
      divergent ecological factors that underlie these metrics. We conclude with
      suggestions to guide the sampling and analysis of herbivorized leaves in the
      fossil record.

PMID- 29657799
TI  - Palaeoecological inferences for the fossil Australian snakes Yurlunggur and
      Wonambi (Serpentes, Madtsoiidae).
AB  - Madtsoiids are among the most basal snakes, with a fossil record dating back to
      the Upper Cretaceous (Cenomanian). Most representatives went extinct by the end
      of the Eocene, but some survived in Australia until the Late Cenozoic. Yurlunggur
      and Wonambi are two of these late forms, and also the best-known madtsoiids to
      date. A better understanding of the anatomy and palaeoecology of these taxa may
      shed light on the evolution and extinction of this poorly known group of snakes
      and on early snake evolution in general. A digital endocast of the inner ear of
      Yurlunggur was compared to those of 81 species of snakes and lizards with known
      ecological preferences using three-dimensional geometric morphometrics. The inner
      ear of Yurlunggur most closely resembles both that of certain semiaquatic snakes
      and that of some semifossorial snakes. Other cranial and postcranial features of
      this snake support the semifossorial interpretation. While the digital endocast
      of the inner ear of Wonambi is too incomplete to be included in a geometric
      morphometrics study, its preserved morphology is very different from that of
      Yurlunggur and suggests a more generalist ecology. Osteology, palaeoclimatic data
      and the palaeobiogeographic distribution of these two snakes are all consistent
      with these inferred ecological differences.

PMID- 29657800
TI  - Nanostructured mesoporous silica: influence of the preparation conditions on the
      physical-surface properties for efficient organic dye uptake.
AB  - A series of ordered mesoporous silica such as MCM-41, SBA-3 and SBA-15, in
      addition to silica micro- (SM) and nano- (SN) mesoporous particles, were
      prepared. The preparation conditions were found to greatly influence the physical
      surface properties including morphological structure, porosity, particle size,
      aggregate average size, surface area, pore size, pore volume and zeta potential
      of the prepared silica, while the chemical structure, predicted from FT-IR
      spectra, and the diffraction patterns, predicted from wide-angle X-ray
      diffraction spectra, were identical. Surface areas of approximately 1500, 1027,
      600, 552 and 317 m2 g-1, pore volumes of 0.93, 0.56, 0.82, 0.72 and 0.5 cm3 g-1,
      radii of 2.48, 2.2, 5.66, 6.6 and 8.98 nm, average aggregate sizes of 56, 65.4,
      220.9, 73, 61.1 and 261 nm and zeta potential values of -32.8, -46.1, -26.3, 
      31.4 and -25.9 mV were obtained for MCM-41, SBA-3, SBA-15, SN and SM,
      respectively. Methylene blue dye uptake capacity of the prepared silica types was
      investigated using the batch technique and, in addition, the most effective
      material was further studied by the column flow system. The kinetics and
      isotherms of the uptake process were studied. The morphological structure,
      surface area, pore radius and zeta potential values were the most correlated
      factors.

PMID- 29657801
TI  - Synthesis of diketopyrrolopyrrole-based polymers with polydimethylsiloxane side
      chains and their application in organic field-effect transistors.
AB  - Linear polydimethylsiloxane (PDMS) was investigated as a solubilizing group for
      pi-conjugated polymers with the aim of combining high solubility in organic
      solvents with the molecular packing in solid films that is advantageous for
      charge transport. Diketopyrrolopyrrole-based copolymers with different contents
      and substitution patterns of the PDMS side chains were synthesized and evaluated
      for application in organic field-effect transistors. The PDMS side chains greatly
      increased the solubility of the polymers and led to shorter d-spacings of the pi
      stacking in the thin films compared with polymers containing conventional
      branched alkyl side chains.

PMID- 29657802
TI  - Total synthesis of rupestine G and its epimers.
AB  - Rupestine G is a guaipyridine sesquiterpene alkaloid isolated from Artemisia
      rupestris L. The total synthesis of rupestine G and its epimers was accomplished
      employing a Suzuki reaction to build a terminal diene moiety. The diene was
      further elaborated into the desired guaipyridine structure by a ring-closing
      metathesis reaction. Over all, rupestine G and its three epimers were obtained as
      a mixture in a sequence of nine linear steps with 18.9% yield. Rupestine G and
      its optically pure isomers were isolated by chiral preparative HPLC and fully
      characterized by 1H ,13C NMR, HRMS, optical rotation value, and experimental and
      calculated electronic circular dichroism spectroscopy.

PMID- 29657803
TI  - Experiments and modelling of rate-dependent transition delay in a stochastic
      subcritical bifurcation.
AB  - Complex systems exhibiting critical transitions when one of their governing
      parameters varies are ubiquitous in nature and in engineering applications.
      Despite a vast literature focusing on this topic, there are few studies dealing
      with the effect of the rate of change of the bifurcation parameter on the tipping
      points. In this work, we consider a subcritical stochastic Hopf bifurcation under
      two scenarios: the bifurcation parameter is first changed in a quasi-steady
      manner and then, with a finite ramping rate. In the latter case, a rate-dependent
      bifurcation delay is observed and exemplified experimentally using a
      thermoacoustic instability in a combustion chamber. This delay increases with the
      rate of change. This leads to a state transition of larger amplitude compared
      with the one that would be experienced by the system with a quasi-steady change
      of the parameter. We also bring experimental evidence of a dynamic hysteresis
      caused by the bifurcation delay when the parameter is ramped back. A surrogate
      model is derived in order to predict the statistic of these delays and to
      scrutinize the underlying stochastic dynamics. Our study highlights the dramatic
      influence of a finite rate of change of bifurcation parameters upon tipping
      points, and it pinpoints the crucial need of considering this effect when
      investigating critical transitions.

PMID- 29657804
TI  - Modelling cointegration and Granger causality network to detect long-term
      equilibrium and diffusion paths in the financial system.
AB  - Microscopic factors are the basis of macroscopic phenomena. We proposed a network
      analysis paradigm to study the macroscopic financial system from a microstructure
      perspective. We built the cointegration network model and the Granger causality
      network model based on econometrics and complex network theory and chose stock
      price time series of the real estate industry and its upstream and downstream
      industries as empirical sample data. Then, we analysed the cointegration network
      for understanding the steady long-term equilibrium relationships and analysed the
      Granger causality network for identifying the diffusion paths of the potential
      risks in the system. The results showed that the influence from a few key stocks
      can spread conveniently in the system. The cointegration network and Granger
      causality network are helpful to detect the diffusion path between the
      industries. We can also identify and intervene in the transmission medium to curb
      risk diffusion.

PMID- 29657805
TI  - A longitudinal study of phenotypic changes in early domestication of house mice.
AB  - Similar phenotypic changes occur across many species as a result of
      domestication, e.g. in pigmentation and snout size. Experimental studies of
      domestication have concentrated on intense and directed selection regimes, while
      conditions that approximate the commensal and indirect interactions with humans
      have not been explored. We examine long-term data on a free-living population of
      wild house mice that have been indirectly selected for tameness by regular
      exposure to humans. In the course of a decade, this mouse population exhibited
      significantly increased occurrence of white patches of fur and decreased head
      length. These phenotypic changes fit to the predictions of the 'domestication
      syndrome'.

PMID- 29657806
TI  - Synthesis of a single-crystal Fe2O3 nanowire array based on stress-induced atomic
      diffusion used for solar water splitting.
AB  - In this study, we successfully fabricated a single-crystal Fe2O3 nanowire array
      based on stress-induced atomic diffusion and used this array as the
      photoelectrode for solar water splitting. With the surface polishing treatment on
      the sample surface, the density of the Fe2O3 nanowire array reached up to 28.75
      wire um-2 when heated for 90 min at 600 degrees C. The photocurrent density of
      the optimized sample was 0.9 mA cm-2 at 1.23 V versus a reversible hydrogen
      electrode in a three-electrode system under AM 1.5 G illumination. The incident
      photon-to-electron conversion efficiency was 6.8% at 400 nm.

PMID- 29657807
TI  - Trophic specialization drives morphological evolution in sea snakes.
AB  - Viviparous sea snakes are the most rapidly speciating reptiles known, yet the
      ecological factors underlying this radiation are poorly understood. Here, we
      reconstructed dated trees for 75% of sea snake species and quantified body shape
      (forebody relative to hindbody girth), maximum body length and trophic diversity
      to examine how dietary specialization has influenced morphological
      diversification in this rapid radiation. We show that sea snake body shape and
      size are strongly correlated with the proportion of burrowing prey in the diet.
      Specialist predators of burrowing eels have convergently evolved a
      'microcephalic' morphotype with dramatically reduced forebody relative to
      hindbody girth and intermediate body length. By comparison, snakes that
      predominantly feed on burrowing gobies are generally short-bodied and small
      headed, but there is no evidence of convergent evolution. The eel specialists
      also exhibit faster rates of size and shape evolution compared to all other sea
      snakes, including those that feed on gobies. Our results suggest that trophic
      specialization to particular burrowing prey (eels) has invoked strong selective
      pressures that manifest as predictable and rapid morphological changes. Further
      studies are needed to examine the genetic and developmental mechanisms underlying
      these dramatic morphological changes and assess their role in sea snake
      speciation.

PMID- 29657808
TI  - Hypothesized diprotomeric enzyme complex supported by stochastic modelling of
      palytoxin-induced Na/K pump channels.
AB  - The sodium-potassium pump (Na+/K+ pump) is crucial for cell physiology. Despite
      great advances in the understanding of this ionic pumping system, its mechanism
      is not completely understood. We propose the use of a statistical model checker
      to investigate palytoxin (PTX)-induced Na+/K+ pump channels. We modelled a system
      of reactions representing transitions between the conformational substates of the
      channel with parameters, concentrations of the substates and reaction rates
      extracted from simulations reported in the literature, based on
      electrophysiological recordings in a whole-cell configuration. The model was
      implemented using the UPPAAL-SMC platform. Comparing simulations and
      probabilistic queries from stochastic system semantics with experimental data, it
      was possible to propose additional reactions to reproduce the single-channel
      dynamic. The probabilistic analyses and simulations suggest that the PTX-induced
      Na+/K+ pump channel functions as a diprotomeric complex in which protein-protein
      interactions increase the affinity of the Na+/K+ pump for PTX.

PMID- 29657809
TI  - Investigation of the antibiofilm capacity of peptide-modified stainless steel.
AB  - Biofilm formation on surfaces is an important research topic in ship tribology
      and medical implants. In this study, dopamine and two types of synthetic peptides
      were designed and attached to 304 stainless steel surfaces, aiming to inhibit the
      formation of biofilms. A combinatory surface modification procedure was applied
      in which dopamine was used as a coupling agent, allowing a strong binding ability
      with the two peptides. X-ray photoelectron spectroscopy (XPS), elemental
      analysis, contact angle measurement and surface roughness test were used to
      evaluate the efficiency of the peptide modification. An antibiofilm assay against
      Staphylococcus aureus was conducted to validate the antibiofilm capacity of the
      peptide-modified stainless steel samples. XPS analysis confirmed that the optimal
      dopamine concentration was 40 ug ml-1 in the coupling reaction. Element analysis
      showed that dopamine and the peptides had bound to the steel surfaces. The
      robustness assay of the modified surface demonstrated that most peptide molecules
      had bound on the surface of the stainless steel firmly. The contact angle of the
      modified surfaces was significantly changed. Modified steel samples exhibited
      improved antibiofilm properties in comparison to untreated and dopamine-only
      counterpart, with the peptide 1 modification displaying the best antibiofilm
      effect. The modified surfaces showed antibacterial capacity. The antibiofilm
      capacity of the modified surfaces was also surface topography sensitive. The
      steel sample surfaces polished with 600# sandpaper exhibited stronger antibiofilm
      capacity than those polished with other types of sandpapers after peptide
      modification. These findings present valuable information for future antifouling
      material research.

PMID- 29657810
TI  - How successful are mutants in multiplayer games with fluctuating environments?
      Sojourn times, fixation and optimal switching.
AB  - Using a stochastic model, we investigate the probability of fixation, and the
      average time taken to achieve fixation, of a mutant in a population of wild
      types. We do this in a context where the environment in which the competition
      takes place is subject to stochastic change. Our model takes into account
      interactions which can involve multiple participants. That is, the participants
      take part in multiplayer games. We find that under certain circumstances, there
      are environmental switching dynamics which minimize the time that it takes for
      the mutants to fixate. To analyse the dynamics more closely, we develop a method
      by which to calculate the sojourn times for general birth-death processes in
      fluctuating environments.

PMID- 29657811
TI  - The evolutionary history of polycotylid plesiosaurians.
AB  - Polycotylidae is a clade of plesiosaurians that appeared during the Early
      Cretaceous and became speciose and abundant early in the Late Cretaceous.
      However, this radiation is poorly understood. Thililua longicollis from the
      Middle Turonian of Morocco is an enigmatic taxon possessing an atypically long
      neck and, as originally reported, a series of unusual cranial features that cause
      unstable phylogenetic relationships for polycotylids. We reinterpret the holotype
      specimen of Thililua longicollis and clarify its cranial anatomy. Thililua
      longicollis possesses an extensive, foramina-bearing jugal, a premaxilla-parietal
      contact and carinated teeth. Phylogenetic analyses of a new cladistic dataset
      based on first-hand observation of most polycotylids recover Thililua and
      Mauriciosaurus as successive lineages at the base of the earliest Late Cretaceous
      polycotyline radiation. A new dataset summarizing the Bauplan of polycotylids
      reveals that their radiation produced an early burst of disparity during the
      Cenomanian-Turonian interval, with marked plasticity in relative neck length, but
      this did not arise as an ecological release following the extinction of
      ichthyosaurs and pliosaurids. This disparity vanished during and after the
      Turonian, which is consistent with a model of 'early experimentation/late
      constraint'. Two polycotylid clades, Occultonectia clade nov. and Polycotylinae,
      survived up to the Maastrichtian, but with low diversity.

PMID- 29657812
TI  - Resurrected 'ancient' Daphnia genotypes show reduced thermal stress tolerance
      compared to modern descendants.
AB  - Understanding how populations adapt to rising temperatures has been a challenge
      in ecology. Research often evaluates multiple populations to test whether local
      adaptation to temperature regimes is occurring. Space-for-time substitutions are
      common, as temporal constraints limit our ability to observe evolutionary
      responses. We employed a resurrection ecology approach to understand how thermal
      tolerance has changed in a Daphnia pulicaria population over time. Temperatures
      experienced by the oldest genotypes were considerably lower than the youngest. We
      hypothesized clones were adapted to the thermal regimes of their respective time
      periods. We performed two thermal shock experiments that varied in length of heat
      exposure. Overall trends revealed that younger genotypes exhibited higher thermal
      tolerance than older genotypes; heat shock protein (hsp70) expression increased
      with temperature and varied among genotypes, but not across time periods. Our
      results indicate temperature may have been a selective factor on this population,
      although the observed responses may be a function of multifarious selection.
      Prior work found striking changes in population genetic structure, and in other
      traits that were strongly correlated with anthropogenic changes. Resurrection
      ecology approaches should help our understanding of interactive effects of
      anthropogenic alterations to temperature and other stressors on the evolutionary
      fate of natural populations.

PMID- 29657813
TI  - Extreme fertilization bias towards freshly inseminated sperm in a species
      exhibiting prolonged female sperm storage.
AB  - The storage of sperm by females across successive reproductive cycles is well
      documented in internal fertilizers, yet the fate of stored sperm when they
      compete with 'new' sperm to fertilize a female's eggs has rarely been considered.
      This gap in our understanding is likely due to the logistical difficulties of
      controlling behavioural interactions during or after mating, which in turn may
      influence how many sperm are inseminated and how stored sperm are ultimately used
      during successive bouts of sperm competition with freshly inseminated sperm.
      Here, we use artificial insemination (AI) in guppies (Poecilia reticulata), a
      polyandrous live-bearing poeciliid fish exhibiting prolonged sperm storage by
      females, to overcome these challenges. The use of AI enables us to control
      potential differential maternal effects (e.g. behaviourally mediated cryptic
      female choice) and specifically test for post-copulatory paternity biases that
      favour either stored or fresh sperm when they compete to fertilize eggs. Our
      paternity analyses revealed the almost complete dominance of freshly inseminated
      sperm over stored sperm, supporting previous studies reporting similar patterns
      following natural matings across successive brood cycles. However, our use of AI,
      which excluded behavioural interactions between males and females, most likely
      generated a far stronger pattern of fresh sperm precedence compared with those
      reported in previous studies, possibly implicating 'cryptic' forms of selection
      by females that may sometimes bolster the success of stored sperm.

PMID- 29657814
TI  - Division rate, cell size and proteome allocation: impact on gene expression noise
      and implications for the dynamics of genetic circuits.
AB  - The cell division rate, size and gene expression programmes change in response to
      external conditions. These global changes impact on average concentrations of
      biomolecule and their variability or noise. Gene expression is inherently
      stochastic, and noise levels of individual proteins depend on synthesis and
      degradation rates as well as on cell-cycle dynamics. We have modelled stochastic
      gene expression inside growing and dividing cells to study the effect of division
      rates on noise in mRNA and protein expression. We use assumptions and parameters
      relevant to Escherichia coli, for which abundant quantitative data are available.
      We find that coupling of transcription, but not translation rates to the rate of
      cell division can result in protein concentration and noise homeostasis across
      conditions. Interestingly, we find that the increased cell size at fast division
      rates, observed in E. coli and other unicellular organisms, buffers noise levels
      even for proteins with decreased expression at faster growth. We then investigate
      the functional importance of these regulations using gene regulatory networks
      that exhibit bi-stability and oscillations. We find that network topology affects
      robustness to changes in division rate in complex and unexpected ways. In
      particular, a simple model of persistence, based on global physiological
      feedback, predicts increased proportion of persister cells at slow division
      rates. Altogether, our study reveals how cell size regulation in response to cell
      division rate could help controlling gene expression noise. It also highlights
      that understanding circuits' robustness across growth conditions is key for the
      effective design of synthetic biological systems.

PMID- 29657815
TI  - Rewilding the world's large carnivores.
AB  - Earth's terrestrial large carnivores form a highly endangered group of species
      with unique conservation challenges. The majority of these species have
      experienced major geographical range contractions, which puts many of them at
      high risk of extinction or of becoming ecologically ineffective. As a result of
      these range contractions and the associated loss of intact predator guilds, the
      ecological effects of these species are now far less widespread and common, with
      inevitable consequences for ecosystem function. Rewilding-which includes
      reintroducing species into portions of their former ranges-is an important
      carnivore conservation tool and means for restoring top-down ecological
      regulation. We conducted a global analysis of potential reintroduction areas. We
      first considered protected areas where one or more large carnivore species have
      been extirpated, identifying a total of 130 protected areas that may be most
      suitable for carnivore reintroduction. These protected areas include sites in
      every major world region, and are most commonly found in Mongolia (n = 13),
      Canada (n = 11), Thailand (n = 9), Namibia (n = 6), Indonesia (n = 6) and
      Australia (n = 6). We considered the sizes of protected areas, their levels of
      protection, the extent of human impacts within and around the protected areas,
      and the status of prey species in the protected areas. Finally, we used the 'last
      of the wild' approach to identify contiguous low human footprint regions within
      the former ranges of each species, identifying an additional 150 areas which
      could be the focus of conservation efforts to create conditions conducive to
      reintroductions. These low footprint regions were most commonly found in the USA
      (n = 14), Russia (n = 14), Canada (n = 10), China (n = 9) and Mauritania (n = 8).
      Together, our results show the global-scale potential for carnivore rewilding
      projects to both conserve these species and provide critical ecological and
      social benefits.

PMID- 29657816
TI  - Evaluation and mechanism of ammonia nitrogen removal using sediments from a
      malodorous river.
AB  - Malodorous rivers are among the major environmental problems of cities in
      developing countries. In addition to the unpleasant smell, the sediments of such
      rivers can act as a sink for pollutants. The excessive amount of ammonia nitrogen
      (NH3-N) in rivers is the main factor that causes the malodour. Therefore, a
      suitable method is necessary for sediment disposition and NH3-N removal in
      malodorous rivers. The sediment in a malodorous river (PS) in Beijing, China was
      selected and modified via calcination (PS-D), Na+ doping (PS-Na) and calcination
      Na+ doping (PS-DNa). The NH3-N removal efficiency using the four sediment
      materials was evaluated, and results indicated that the NH3-N removal efficiency
      using the modified sediment materials could reach over 60%. PS-DNa achieved the
      highest NH3-N removal efficiency (90.04%). The kinetics study showed that the
      pseudo-second-order model could effectively describe the sorption kinetics and
      that the exterior activated site had the main function of P sorption. The results
      of the sorption isotherms indicated that the maximum sorption capacities of PS
      Na, PS-D and PS-DNa were 0.343, 0.831 and 1.113 mg g-1, respectively, and a high
      temperature was favourable to sorption. The calculated thermodynamic parameters
      suggested that sorption was a feasible or spontaneous (DeltaG < 0), entropy
      driven (DeltaS > 0), and endothermic (DeltaH > 0) reaction.

PMID- 29657817
TI  - A networked voting rule for democratic representation.
AB  - We introduce a general framework for exploring the problem of selecting a
      committee of representatives with the aim of studying a networked voting rule
      based on a decentralized large-scale platform, which can assure a strong
      accountability of the elected. The results of our simulations suggest that this
      algorithm-based approach is able to obtain a high representativeness for
      relatively small committees, performing even better than a classical voting rule
      based on a closed list of candidates. We show that a general relation between
      committee size and representatives exists in the form of an inverse square root
      law and that the normalized committee size approximately scales with the inverse
      of the community size, allowing the scalability to very large populations. These
      findings are not strongly influenced by the different networks used to describe
      the individuals' interactions, except for the presence of few individuals with
      very high connectivity which can have a marginal negative effect in the committee
      selection process.

PMID- 29657818
TI  - Developmental plasticity of the stress response in female but not in male
      guppies.
AB  - To survive, animals must respond appropriately to stress. Stress responses are
      costly, so early-life experiences with potential stressors could adaptively
      tailor adult stress responses to local conditions. However, how multiple
      stressors influence the development of the stress response remains unclear, as is
      the role of sex. Trinidadian guppies (Poecilia reticulata) are small fish with
      extensive life-history differences between the sexes and population variation in
      predation pressure and social density. We investigated how sex and early-life
      experience influence hormonal stress responses by manipulating conspecific
      density and perceived predation risk during development. In adults, we sampled
      cortisol twice to measure initial release and change over time in response to a
      recurring stressor. The sexes differed considerably in their physiological stress
      response. Males released more cortisol for their body mass than females and did
      not reduce cortisol release over time. By contrast, all females, except those
      reared at high density together with predation cues, reduced cortisol release
      over time. Cortisol responses of males were thus less dynamic in response to
      current circumstances and early-life experiences than females, consistent with
      life-history differences between the sexes. Our study underscores the importance
      of early-life experiences, interacting ecological factors and sex differences in
      the organization of the stress response.

PMID- 29657819
TI  - Substrate texture affects female cricket walking response to male calling song.
AB  - Field crickets are extensively used as a model organism to study female
      phonotactic walking behaviour, i.e. their attraction to the male calling song.
      Laboratory-based phonotaxis experiments generally rely on arena or trackball
      based settings; however, no attention has been paid to the effect of substrate
      texture on the response. Here, we tested phonotaxis in female Gryllus
      bimaculatus, walking on trackballs machined from methyl-methacrylate foam with
      different cell sizes. Surface height variations of the trackballs, due to the
      cellular composition of the material, were measured with profilometry and
      characterized as smooth, medium or rough, with roughness amplitudes of 7.3, 16
      and 180 um. Female phonotaxis was best on a rough and medium trackball surface, a
      smooth surface resulted in a significant lower phonotactic response. Claws of the
      cricket foot were crucial for effective walking. Females insert their claws into
      the surface pores to allow mechanical interlocking with the substrate texture and
      a high degree of attachment, which cannot be established on smooth surfaces.
      These findings provide insight to the biomechanical basis of insect walking and
      may inform behavioural studies that the surface texture on which walking insects
      are tested is crucial for the resulting behavioural response.

PMID- 29657820
TI  - Neopterygian phylogeny: the merger assay.
AB  - The phylogenetic relationships of the recently described genus ?Ticinolepis from
      the Middle Triassic of the Monte San Giorgio are explored through cladistic
      analyses of the so far largest morphological dataset for fossil actinopterygians,
      including representatives of the crown-neopterygian clades Halecomorphi,
      Ginglymodi and Teleostei, and merging the characters from previously published
      systematic studies together with newly proposed characters. ?Ticinolepis is
      retrieved as the most basal Ginglymodi and our results support the monophyly of
      Teleostei and Holostei, as well as Halecomorphi and Ginglymodi within the latter
      clade. The patterns of relationships within these clades mostly agree with those
      of previous studies, although a few important differences require future
      research. According to our results, ionoscopiforms are not monophyletic, caturids
      are not amiiforms and leptolepids and luisiellids form a monophyletic clade. Our
      phylogenetic hypothesis confirms the rapid radiation of the holostean clades
      Halecomorphi and Ginglymodi during the Early and Middle Triassic and the
      radiation of pholidophoriform teleosts during the Late Triassic. Crown-group
      Halecomorphi have an enormous ghost lineage throughout half of the Mesozoic, but
      ginglymodians and teleosts show a second radiation during the Early Jurassic. The
      crown-groups of Halecomorphi, Ginglymodi and Teleostei originated within parallel
      events of radiation during the Late Jurassic.

PMID- 29657821
TI  - Explicit solutions to correlation matrix completion problems, with an application
      to risk management and insurance.
AB  - We derive explicit solutions to the problem of completing a partially specified
      correlation matrix. Our results apply to several block structures for the
      unspecified entries that arise in insurance and risk management, where an
      insurance company with many lines of business is required to satisfy certain
      capital requirements but may have incomplete knowledge of the underlying
      correlation matrix. Among the many possible completions, we focus on the one with
      maximal determinant. This has attractive properties and we argue that it is
      suitable for use in the insurance application. Our explicit formulae enable easy
      solution of practical problems and are useful for testing more general algorithms
      for the maximal determinant correlation matrix completion problem.

PMID- 29657822
TI  - Increasing cell-device adherence using cultured insect cells for receptor-based
      biosensors.
AB  - Field-effect transistor (FET)-based biosensors have a wide range of applications,
      and a bio-FET odorant sensor, based on insect (Sf21) cells expressing insect
      odorant receptors (ORs) with sensitivity and selectivity, has emerged. To fully
      realize the practical application of bio-FET odorant sensors, knowledge of the
      cell-device interface for efficient signal transfer, and a reliable and low-cost
      measurement system using the commercial complementary metal-oxide semiconductor
      (CMOS) foundry process, will be indispensable. However, the interfaces between
      Sf21 cells and sensor devices are largely unknown, and electrode materials used
      in the commercial CMOS foundry process are generally limited to aluminium, which
      is reportedly toxic to cells. In this study, we investigated Sf21 cell-device
      interfaces by developing cross-sectional specimens. Calcium imaging of Sf21 cells
      expressing insect ORs was used to verify the functions of Sf21 cells as odorant
      sensor elements on the electrode materials. We found that the cell-device
      interface was approximately 10 nm wide on average, suggesting that the adhesion
      mechanism of Sf21 cells may differ from that of other cells. These results will
      help to construct accurate signal detection from expressed insect ORs using FETs.

PMID- 29657823
TI  - A biogeographic perspective on the evolution of fire syndromes in pine trees
      (Pinus: Pinaceae).
AB  - Our goals were to explore the relationship between biogeography and the evolution
      of fire-adaptive syndromes in the genus Pinus. We used a previously published
      time-calibrated phylogeny and conducted ancestral trait reconstruction to
      estimate the likely timing of diversification in Pinus, and to determine when
      fire-adaptive syndromes evolved in the lineage. To explore trait conservation
      among fire syndromes and to investigate historical biogeography, we constructed
      ancestral state reconstructions using the program RASP and estimated the degree
      of conservatism for fire-adapted traits in the program BaTS. Our reconstructions
      suggest that the Bering land bridge, which connected North America and Asia,
      probably played a major role in early pine evolution. Our estimates indicated
      that fire-adaptive syndromes seem to have evolved more frequently in New World
      taxa and probably are related to the uplift of major North American mountain
      ranges. Our data suggest that certain geographically widespread adaptations to
      fire evolved repeatedly, possibly due to localized changes in climate and
      environment, rather than resulting from large dispersal events of pre-adapted
      individuals.

PMID- 29657824
TI  - Genome-wide analyses of the bHLH superfamily in crustaceans: reappraisal of
      higher-order groupings and evidence for lineage-specific duplications.
AB  - The basic helix-loop-helix (bHLH) proteins represent a key group of transcription
      factors implicated in numerous eukaryotic developmental and signal transduction
      processes. Characterization of bHLHs from model species such as humans, fruit
      flies, nematodes and plants have yielded important information on their functions
      and evolutionary origin. However, relatively little is known about bHLHs in non
      model organisms despite the availability of a vast number of high-throughput
      sequencing datasets, enabling previously intractable genome-wide and cross
      species analyses to be now performed. We extensively searched for bHLHs in 126
      crustacean species represented across major Crustacea taxa and identified 3777
      putative bHLH orthologues. We have also included seven whole-genome datasets
      representative of major arthropod lineages to obtain a more accurate prediction
      of the full bHLH gene complement. With focus on important food crop species from
      Decapoda, we further defined higher-order groupings and have successfully
      recapitulated previous observations in other animals. Importantly, we also
      observed evidence for lineage-specific bHLH expansions in two basal crustaceans
      (branchiopod and copepod), suggesting a mode of evolution through gene
      duplication as an adaptation to changing environments. In-depth analysis on bHLH
      PAS members confirms the phenomenon coined as 'modular evolution' (independently
      evolved domains) typically seen in multidomain proteins. With the amphipod
      Parhyale hawaiensis as the exception, our analyses have focused on crustacean
      transcriptome datasets. Hence, there is a clear requirement for future analyses
      on whole-genome sequences to overcome potential limitations associated with
      transcriptome mining. Nonetheless, the present work will serve as a key resource
      for future mechanistic and biochemical studies on bHLHs in economically important
      crustacean food crop species.

PMID- 29657825
TI  - Diversity of late Neogene Monachinae (Carnivora, Phocidae) from the North
      Atlantic, with the description of two new species.
AB  - While the diversity of 'southern seals', or Monachinae, in the North Atlantic
      realm is currently limited to the Mediterranean monk seal, Monachus monachus,
      their diversity was much higher during the late Miocene and Pliocene. Although
      the fossil record of Monachinae from the North Atlantic is mainly composed of
      isolated specimens, many taxa have been erected on the basis of fragmentary and
      incomparable specimens. The humerus is commonly considered the most diagnostic
      postcranial bone. The research presented in this study limits the selection of
      type specimens for different fossil Monachinae to humeri and questions fossil
      taxa that have other types of bones as type specimens, such as for Terranectes
      parvus. In addition, it is essential that the humeri selected as type specimens
      are (almost) complete. This questions the validity of partial humeri selected as
      type specimens, such as for Terranectes magnus. This study revises Callophoca
      obscura, Homiphoca capensis and Pliophoca etrusca, all purportedly known from the
      Lee Creek Mine, Aurora, North Carolina, in addition to their respective type
      localities in Belgium, South Africa and Italy, respectively. C. obscura is
      retained as a monachine seal taxon that lived both on the east coast of North
      America and in the North Sea Basin. However, H. capensis from North America
      cannot be identified beyond the genus level, and specimens previously assigned to
      Pl. etrusca from North America clearly belong to different taxa. Indeed, we also
      present new material and describe two new genera of late Miocene and Pliocene
      Monachinae from the east coast of North America: Auroraphoca atlantica nov. gen.
      et nov. sp., and Virginiaphoca magurai nov. gen. et nov. sp. This suggests less
      faunal interchange of late Neogene Monachinae between the east and west coasts of
      the North Atlantic than previously expected.

PMID- 29657826
TI  - Heel impact forces during barefoot versus minimally shod walking among Tarahumara
      subsistence farmers and urban Americans.
AB  - Despite substantial recent interest in walking barefoot and in minimal footwear,
      little is known about potential differences in walking biomechanics when unshod
      versus minimally shod. To test the hypothesis that heel impact forces are similar
      during barefoot and minimally shod walking, we analysed ground reaction forces
      recorded in both conditions with a pedography platform among indigenous
      subsistence farmers, the Tarahumara of Mexico, who habitually wear minimal
      sandals, as well as among urban Americans wearing commercially available minimal
      sandals. Among both the Tarahumara (n = 35) and Americans (n = 30), impact peaks
      generated in sandals had significantly (p < 0.05) higher force magnitudes, slower
      loading rates and larger vertical impulses than during barefoot walking. These
      kinetic differences were partly due to individuals' significantly greater
      effective mass when walking in sandals. Our results indicate that, in general,
      people tread more lightly when walking barefoot than in minimal footwear. Further
      research is needed to test if the variations in impact peaks generated by walking
      barefoot or in minimal shoes have consequences for musculoskeletal health.

PMID- 29657827
TI  - Vertical exploration and dimensional modularity in mice.
AB  - Exploration is a central component of animal behaviour studied extensively in
      rodents. Previous tests of free exploration limited vertical movement to rearing
      and jumping. Here, we attach a wire mesh to the arena wall, allowing vertical
      exploration. This provides an opportunity to study the morphogenesis of behaviour
      along the vertical dimension, and examine the context in which it is performed.
      In the current set-up, the mice first use the doorway as a point reference for
      establishing a borderline linear path along the circumference of the arena floor,
      and then use this path as a linear reference for performing horizontal forays
      towards the centre (incursions) and vertical forays on the wire mesh (ascents).
      Vertical movement starts with rearing on the wall, and commences with straight
      vertical ascents that increase in extent and complexity. The mice first reach the
      top of the wall, then mill about within circumscribed horizontal sections, and
      then progress horizontally for increasingly longer distances on the upper edge of
      the wire mesh. Examination of the sequence of borderline segments, incursions and
      ascents reveals dimensional modularity: an initial series (bout) of borderline
      segments precedes alternating bouts of incursions and bouts of ascents, thus
      exhibiting sustained attention to each dimension separately. The exhibited
      separate growth in extent and in complexity of movement and the sustained
      attention to each of the three dimensions disclose the mice's modular perception
      of this environment and validate all three as natural kinds.

PMID- 29657829
TI  - Reviewers in 2017.

PMID- 29657828
TI  - An objective in vivo diagnostic method for inflammatory bowel disease.
AB  - Inflammatory damage to the bowel, as occurs in inflammatory bowel disease (IBD),
      is debilitating to patients. In both patients and animal experimental models,
      histological analyses of biopsies and endoscopic examinations are used to
      evaluate the disease state. However, such measurements often have delays and are
      invasive, while endoscopy is not quantitatively objective. Therefore, a real-time
      quantitative method to assess compromised mucosal barrier function is
      advantageous. We investigated the correlation of in vivo changes in electrical
      transmural impedance with histological measures of inflammation. Four platinum
      (Pt) ball electrodes were placed in the lumen of the rat small intestine, with a
      return electrode under the skin. Electrodes placed within the non-inflamed
      intestine generated stable impedances during the 3 h testing period. Following an
      intraluminal injection of 2,4,6-trinitrobenzene sulfonic acid (TNBS), an
      established animal model of IBD, impedances in the inflamed region significantly
      decreased relative to a region not exposed to TNBS (p < 0.05). Changes in
      intestinal transmural impedance were correlated (p < 0.05) with histologically
      assessed damage to the mucosa and increases in neutrophil, eosinophil and T-cell
      populations at 3 h compared with tissue from control regions. This quantitative,
      real-time assay may have application in the diagnosis and clinical management of
      IBD.

PMID- 29657830
TI  - Conversion to seronegative status after abatacept treatment in patients with
      early and poor prognostic rheumatoid arthritis is associated with better
      radiographic outcomes and sustained remission: post hoc analysis of the AGREE
      study.
AB  - Objective: To evaluate the effects of the T-cell costimulation blocker abatacept
      on anti-citrullinated protein antibodies (ACPA) and rheumatoid factor (RF) in
      early rheumatoid arthritis (RA), and associations between changes in serological
      status and clinical response. Methods: Post hoc analysis of the phase III AGREE
      study in methotrexate (MTX)-naive patients with early RA and poor prognostic
      factors. Patients were randomised to abatacept (~10 mg/kg intravenously according
      to weight range) or placebo, plus MTX over 12 months followed by open-label
      abatacept plus MTX for 12 months. Autoantibody titres were determined by ELISA at
      baseline and months 6 and 12 (double-blind phase). Conversion to seronegative
      status and its association with clinical response were assessed at months 6 and
      12. Results: Abatacept plus MTX was associated with a greater decrease in ACPA
      (but not RF) titres and higher rates of both ACPA and RF conversion to
      seronegative status versus MTX alone. More patients converting to ACPA
      seronegative status receiving abatacept plus MTX achieved remission according to
      Disease Activity Score in 28 joints (C-reactive protein) or Clinical Disease
      Activity Index than patients who remained ACPA seropositive. Patients who
      converted to ACPA seronegative status treated with abatacept plus MTX had a
      greater probability of achieving sustained remission and less radiographic
      progression than MTX alone or patients who remained ACPA seropositive (either
      treatment). Conclusions: Treatment with abatacept plus MTX was more likely to
      induce conversion to ACPA/RF seronegative status in patients with early, erosive
      RA. Conversion to ACPA seronegative status was associated with better clinical
      and radiographic outcomes. Trial registration number: NCT00122382.

PMID- 29657831
TI  - Pharmacodynamic and pharmacokinetic effects and safety of verinurad in
      combination with febuxostat in adults with gout: a phase IIa, open-label study.
AB  - Objective: Verinurad (RDEA3170) is a high-affinity, selective URAT1 inhibitor in
      development for treating gout and asymptomatic hyperuricaemia. This study
      evaluated the pharmacodynamics, pharmacokinetics and safety of verinurad in
      combination with febuxostat in adults with gout. Methods: The phase IIa, open
      label, multicentre study randomised 64 subjects into one of five cohorts to
      receive febuxostat (40 or 80 mg) alone or in combination with verinurad 2.5-20
      mg. Serial plasma/serum and urine samples were assayed for verinurad and uric
      acid. Safety was assessed by adverse events, chemistry panels, ECGs and physical
      examinations. Results: Serum pharmacodynamic data demonstrated the maximum
      percent decrease in serum urate (sUA) from baseline (Emax) at 8-12 hours after
      dosing. Verinurad with febuxostat decreased sUA in a dose-dependent manner. Emax
      for verinurad with febuxostat 40 mg ranged from 52% to 77% vs 42% for febuxostat
      40 mg alone; Emax for verinurad with febuxostat 80 mg was 62%-82% vs 55% for
      febuxostat 80 mg alone. Urinary uric acid excretion rate was reduced below
      baseline by febuxostat alone and was comparable to baseline for verinurad with
      febuxostat. Verinurad plasma exposure increased with dose and was comparable when
      combined with febuxostat. No drug-drug interactions were observed. Verinurad was
      well tolerated with no clinically meaningful changes in laboratory values.
      Conclusion: Verinurad administered with febuxostat produced dose-dependent
      decreases in sUA while maintaining urinary uric acid levels comparable to
      baseline. These dose combinations of verinurad and febuxostat were generally well
      tolerated. These data support continued investigation of oral verinurad in
      patients with gout. Trial registration number: NCT02246673.

PMID- 29657832
TI  - Predictive value of serum calprotectin (S100A8/A9) for clinical response after
      starting or tapering anti-TNF treatment in patients with rheumatoid arthritis.
AB  - Objectives: Calprotectin (S100A8/A9) has been correlated with disease activity in
      rheumatoid arthritis (RA). The aim of this study was to investigate the
      predictive value of serum calprotectin for clinical response after starting and
      tapering anti-tumour necrosis factor treatment in RA. Methods: Serum samples and
      clinical outcomes were derived from two longitudinal RA studies.At baseline
      (starting or tapering of adalimumab or etanercept), calprotectin levels were
      determined by ELISA. In the Biologic Individual Optimised Treatment Outcome
      Prediction (BIO-TOP) study, treatment effect was assessed after 6 months using
      the European League Against Rheumatism (EULAR) response criteria. In the Dose
      Reduction Strategies of Subcutaneous TNF Inhibitors (DRESS) study, patients were
      classified at 18 months as being successfully dose reduced, discontinued or not
      able to reduce the dose. Area under the receiver operating characteristic curves
      (AUC) were generated to evaluate the predictive value of calprotectin and
      logistic prediction models were created to assess its added value. Results: In
      the BIO-TOP study, calprotectin levels were higher in responders (n=50: 985 ng/mL
      (p25-p75: 558-1417)) compared with non-responders (n=75: 645 ng/mL (p25-p75: 415
      973), p=0.04).AUC for predicting EULAR good response was 0.61 (95% CI 0.50 to
      0.71). The prediction model with calprotectin (AUC 0.77, 95% CI 0.68 to 0.85)
      performed similarly to the baseline model (AUC 0.74, 95% CI 0.65 to 0.82,
      p=0.29). In the DRESS study, calprotectin levels were similar between the three
      groups (n=47; n=19; n=36) and calprotectin was not predictive for clinical
      response after tapering. Conclusions: Serum calprotectin has some predictive
      value for clinical response after starting anti-TNF treatment, although it has no
      added value to other clinical factors. In patients with low disease activity,
      serum calprotectin is not predictive for clinical response after tapering anti
      TNF treatment. Trial registration number: NTR4647 (BIO-TOP study) and NTR3216
      (DRESS study); Pre-results.

PMID- 29657833
TI  - Paradoxical arthritis occurring during anti-TNF in patients with inflammatory
      bowel disease: histological and immunological features of a complex synovitis.
AB  - Objective: Paradoxical arthritis under tumour necrosis factor inhibitor (TNF-i)
      for inflammatory bowel disease (IBD) has been described. This study aims to
      evaluate the histological features of paired synovial tissue (ST) and colonic
      mucosa (CM) tissue in patients with IBD developing paradoxical arthritis under
      TNF-i. Methods: Patients with IBD without history of coexisting joint involvement
      who developed arthritis under TNF-i were enrolled. Each patient underwent ST
      biopsy and ileocolonoscopy with CM biopsies. ST and CM paired samples were
      stained through immunohistochemistry (IHC) for CD68, CD21, CD20, CD3 and CD117.
      Clinical and immunological parameters (anticitrullinated peptides antibodies
      (ACPA)-immunoglobulin (Ig)M/IgA rheumatoid factor (RF)) were collected. Psoriatic
      arthritis (PsA) and ACPA/IgM-RF/IgA-RF negative rheumatoid arthritis (RA) were
      enrolled as comparison. Results: 10 patients with IBD (age 46.0+/-9.7 years,
      13.2+/-9.9 years of disease duration, 2.5+/-1.6 years of TNF-i exposure, six with
      Crohn's disease and four with ulcerative colitis, respectively) were studied. At
      ST level, IHC revealed that patients with IBD with paradoxical arthritis showed
      more similar histological findings in terms of synovial CD68+, CD21+, CD20+, CD3+
      and CD117+ cells compared with PsA than ACPA/IgM-RF/IgA-RF negative RA. Analysing
      the CM specimens, patients with IBD showed the presence of CD68+, CD3+, CD117+
      and CD20+ cells in 100%, 70%, 60% and 50% of cases, respectively, despite
      endoscopic remission. Finally, addition of conventional disease-modifying
      antirheumatic drugs and switch to ustekinumab were more effective than swapping
      into different TNF-i in patients with IBD with paradoxical arthritis. Conclusion:
      Patients with IBD may develop histologically proven synovitis during TNF-i,
      comparable to PsA. The inhibition of inflammatory pathways alternative to TNF
      (IL12/1L23) may be an effective therapeutic option for severe paradoxical
      articular manifestations.

PMID- 29657834
TI  - Use of EHR-based simulation to diagnose aetiology of information gathering issues
      in struggling learners: a proof of concept study.
AB  - Learners who struggle with clinical decision making are often the most
      challenging to identify and remediate. While for some learners, struggles can be
      directly traced to a poor knowledge base, for many others, it is more difficult
      to understand the reason for their struggles. One of the main component of
      effective decision making is access to accurate and complete clinical
      information. The electronic health record (EHR) is the main source of clinical
      information and, with its widespread adoption, has come increased realisation
      that a large fraction of users have difficulty in effectively gathering and
      subsequently processing information out of the EHR. We previously documented that
      high-fidelity EHR-based simulation improves EHR usability and, when combined with
      eye and screen tracking, generates important measures of usability. We
      hypothesised that the same simulation exercise could help distinguish whether
      learners had difficulty in knowledge, information gathering or information
      processing. We report the results of the first three struggling learners who
      participated in this exercise. In each case, the simulation was able to
      'diagnose' the aetiology for the learners' struggle and assist in formulating an
      appropriate solution. We suggest that high-fidelity EHR-based simulation can be a
      powerful tool in the standard approach to understanding struggling learners.

PMID- 29657835
TI  - What does patient engagement mean for Canadian National Transplant Research
      Program Researchers?
AB  - Plain English summary: In recent years, the importance of involving patients in
      research has been increasingly recognized because it increases the relevance and
      quality of research, facilitates recruitment, enhances public trust and allows
      for more effective dissemination of results. The Canadian National Transplant
      Research Program (CNTRP) is an interdisciplinary research team looking at a
      variety of issues related to organ and tissue donation and transplantation. The
      aim of this study was to gather the perspectives of CNTRP researchers on engaging
      patients in research.We conducted interviews with 10 researchers who attended a
      national workshop on priority-setting in organ donation and transplant research.
      The researchers viewed patient engagement in research as necessary and important.
      They also considered that patients could be engaged at every step of the research
      process. Participants in this study identified scientific language, time, money,
      power imbalance, patient selection and risk of tokenism as potential barriers to
      patient engagement in research. Training, adequate resources and support from the
      institution were identified as facilitators of patient engagement.This study
      showed a positive attitude among researchers in the field of organ donation and
      transplantation. Further studies are needed to study the implementation and
      impact of patient engagement in research within the CNTRP. Abstract: Background
      Involving patients in research has been acknowledged as a way to enhance the
      quality, relevance and transparency of medical research. No previous studies have
      looked at researchers' perspectives on patient engagement (PE) in organ donation
      and transplant research in Canada. Objective The aim of this study was to gather
      the perspectives of Canadian National Transplant Research Program (CNTRP)
      researchers on PE in research. Methods We conducted semi-structured interviews
      with ten researchers who attended a national workshop on priority-setting in
      organ donation and transplant research. The interviews were digitally recorded
      and transcribed verbatim, and the transcripts were subjected to qualitative
      thematic and content analyses. Results The researchers viewed PE in research as
      necessary and important. PE was a method to incorporate the voice of the patient.
      They also considered that patients could be engaged at every step of the research
      process. The following were identified as the main barriers to PE in research:
      (i) scientific jargon; (ii) resources (time and money); (iii) tokenism; (iv)
      power imbalance; and (v) patient selection. Facilitating factors included (i)
      training for patients and researchers, (ii) adequate resources and (iii)
      institutional support. Conclusion This study revealed a favourable attitude and
      willingness among CNTRP researchers to engage and partner with patients in
      research. Further studies are needed to assess the implementation of PE strategy
      within the CNTRP and its impact.

PMID- 29657836
TI  - Resistive index of ophthalmic artery correlates with retinal pigment epithelial
      alterations on spectral domain optical coherence tomography in diabetic
      retinopathy.
AB  - Background: Retinal pigment epithelium (RPE) plays a significant role in
      maintenance of integrity of retinal photoreceptors and choriocapillaries. RPE
      derives its blood supply through ophthalmic artery (OA) via choriocapillaries.
      RPE topographic alterations have been observed to be associated with severity of
      retinopathy. The present study was undertaken to assess the correlation between
      resistive index (RI) of the OA with RPE topographic alterations on Spectral
      Domain optical coherence tomography (SD-OCT), to our knowledge, it is for the
      first time. Methods: A tertiary care center based cross-sectional study was
      undertaken after informed consent. Sample size was calculated using 95%
      confidence interval. Seventy five consecutive cases of type 2 diabetes mellitus
      between the ages of 40 and 70 years were included. The cases were divided into
      three groups according to Early Treatment Diabetic Retinopathy Study
      classification: diabetes mellitus with no retinopathy (No DR) (n = 24); non
      proliferative diabetic retinopathy (n = 27); and proliferative diabetic
      retinopathy (n = 24). Healthy control subjects of similar age group were included
      (n = 24). RI in OA was studied using Color Doppler imaging. Grades of RPE
      topographic alterations and retinal photoreceptor ellipsoid zone (EZ) disruption
      were studied using SD-OCT. Data was analysed using Chi square (chi2) test,
      analysis of variance (ANOVA), Pearson correlation analysis and Neuman-Keuls test.
      Results: LogMAR best corrected visual acuity was found to increase significantly
      with the severity of DR (F = 105.74, p < 0.001). ANOVA revealed a significant
      increase in RI of OA (F = 14.23, p < 0.001) with severity of diabetic
      retinopathy. chi2 test revealed significant increase in grades of RPE alterations
      (chi2 = 71.83, p < 0.001) and EZ disruption (chi2 = 60.59, p < 0.001) with the
      severity of diabetic retinopathy. Pearson correlation analyses revealed a
      significant positive correlation between RI of OA with grades of RPE alterations
      (r = 0.48, p < 0.001) and also between grades of RPE alterations and EZ
      disruption (r = 0.82, p < 0.001). Conclusions: Decrease in ocular blood flow
      resulting from an increase in RI of OA correlates with severity of DR and grades
      of topographic alterations in RPE. Integrity of EZ was observed to be dependent
      on RPE.

PMID- 29657837
TI  - Inter- and intracontinental migrations and local differentiation have shaped the
      contemporary epidemiological landscape of canine parvovirus in South America.
AB  - Canine parvovirus (CPV) is a fast-evolving single-stranded DNA virus that causes
      one of the most significant infectious diseases of dogs. Although the virus
      dispersed over long distances in the past, current populations are considered to
      be spatially confined and with only a few instances of migration between specific
      localities. It is unclear whether these dynamics occur in South America where
      global studies have not been performed. The aim of this study is to analyze the
      patterns of genetic variability in South American CPV populations and explore
      their evolutionary relationships with global strains. Genomic sequences of sixty
      three strains from South America and Europe were generated and analyzed using a
      phylodynamic approach. All the obtained strains belong to the CPV-2a lineage and
      associate with global strains in four monophyletic groups or clades. European and
      South American strains from all the countries here analyzed are representative of
      a widely distributed clade (Eur-I) that emerged in Southern Europe during 1990-98
      to later spread to South America in the early 2000s. The emergence and spread of
      the Eur-I clade were correlated with a significant rise in the CPV effective
      population size in Europe and South America. The Asia-I clade includes strains
      from Asia and Uruguay. This clade originated in Asia during the late 1980s and
      evolved locally before spreading to South America during 2009-10. The third clade
      (Eur-II) comprises strains from Italy, Brazil, and Ecuador. This clade appears in
      South America as a consequence of an early introduction from Italy to Ecuador in
      the middle 1980s and has experienced extensive local genetic differentiation.
      Some strains from Argentina, Uruguay, and Brazil constitute an exclusive South
      American clade (SA-I) that emerged in Argentina in the 1990s. These results
      indicate that the current epidemiological scenario is a consequence of inter- and
      intracontinental migrations of strains with different geographic and temporal
      origins that set the conditions for competition and local differentiation of CPV
      populations. The coexistence and interaction of highly divergent strains are the
      main responsible for the drastic epidemiological changes observed in South
      America in the last two decades. This highlights the threat of invasion from
      external sources and the importance of whole-genome resolution to robustly infer
      the origin and spread of new CPV variants. From a taxonomic standpoint, the
      findings herein show that the classification system that uses a single amino acid
      to identify variants (2a, 2b, and 2c) within the CPV-2a lineage does not reflect
      phylogenetic relationships and is not suitable to analyze CPV evolution. In this
      regard, the identification of clades or sublineages within circulating CPV
      strains is the first step towards a genetic and evolutionary classification of
      the virus.

PMID- 29657838
TI  - Collective cell migration over long time scales reveals distinct phenotypes.
AB  - Introduction: Migratory phenotypes of metastasizing tumor cells include single
      and collective cell migration. While migration of tumor cells is generally less
      cooperative than that of normal epithelial cells, our understanding of precisely
      how they differ in long time behavior is incomplete. Objectives: We measure in a
      model system how cancer progression affects collective migration on long time
      scales, and determine how perturbation of cell-cell adhesions, specifically
      reduced E-cadherin expression, affects the collective migration phenotype.
      Methods: Time lapse imaging of cellular sheets and particle image velocimetry
      (PIV) are used to quantitatively study the dynamics of cell motion over ten
      hours. Long time dynamics are measured via finite time Lyapunov exponents (FTLE)
      and changes in FTLE with time. Results: We find that non-malignant MCF10A cells
      are distinguished from malignant MCF10CA1a cells by both their short time
      (minutes) and long time (hours) dynamics. In addition, short time dynamics
      distinguish non-malignant E-cadherin knockdown cells from the control, but long
      time dynamics and increasing spatial correlations remain unchanged. Discussion:
      Epithelial sheet collective behavior includes long time dynamics that cannot be
      captured by metrics that assess cooperativity based on short time dynamics, such
      as instantaneous speed or directionality. The use of metrics incorporating
      migration data over hours instead of minutes allows us to more precisely describe
      how E-cadherin, a clinically relevant adhesion molecule, affects collective
      migration. We predict that the long time scale metrics described here will be
      more robust and predictive of malignant behavior than analysis of instantaneous
      velocity fields alone.

PMID- 29657839
TI  - Current concepts for aligning knee implants: patient-specific or systematic?
AB  - Mechanical or anatomical alignment techniques create a supposedly
      'biomechanically friendly' but often functionally limited prosthetic
      knee.Alternative techniques for alignment in total knee arthroplasty (TKA) aim at
      being more anatomical and patient-specific, aiming to improve functional outcomes
      after TKA.The kinematic alignment (KA) technique for TKA has shown good early
      clinical outcomes. Its role in extreme anatomical variation remains to be
      defined.The restricted KA technique for TKA might be a reasonable option for
      patients with extreme anatomical variation.While unicompartmental knee
      arthroplasty (UKA) has many advantages over TKA, the revision rate remains higher
      compared with TKA. One major explanation is the relative ease with which a UKA
      can be converted to a TKA, compared with revising a TKA. This can be considered
      as an additional advantage of UKA. Another reason is that surgeons favour
      revising a UKA to a TKA in cases of degeneration of the other femorotibial
      compartment rather than performing a relatively simple re-operation of the knee
      by doing an additional UKA (staged bi-UKA). Cite this article: EFORT Open Rev
      2018;3:1-6. DOI: 10.1302/2058-5241.3.170021.

PMID- 29657840
TI  - Third-generation pure alumina and alumina matrix composites in total hip
      arthroplasty: What is the evidence?
AB  - Wear, corrosion and periprosthetic osteolysis are important causes of failure in
      joint arthroplasty, especially in young patients.Ceramic bearings, developed 40
      years ago, are an increasingly popular choice in hip arthroplasty. New
      manufacturing procedures have increased the strength and reliability of ceramic
      materials and reduced the risk of complications.In recent decades, ceramics made
      of pure alumina have continuously improved, resulting in a surgical-grade
      material that fulfills clinical requirements.Despite the track record of safety
      and long-term results, third-generation pure alumina ceramics are being replaced
      in clinical practice by alumina matrix composites, which are composed of alumina
      and zirconium.In this review, the characteristics of both materials are
      discussed, and the long-term results with third-generation alumina-on-alumina
      bearings and the associated complications are compared with those of other
      available ceramics. Cite this article: EFORT Open Rev 2018;3:7-14. DOI:
      10.1302/2058-5241.3.170034.

PMID- 29657841
TI  - Locked posterior dislocation of the shoulder: A systematic review.
AB  - Locked posterior dislocation of the shoulder is very rare. Seizures and trauma
      are the most common causes of this injury.There is no current benchmark treatment
      strategy for these rare cases.This study has shown that reconstruction of the
      shoulder joint in an anatomical way in acute and chronic cases up to 16 weeks
      provides good results.The purpose of this study is to evaluate the results of
      different treatment procedures with outcomes and to compare the results of the
      same procedures in acute and chronic cases. Cite this article: EFORT Open Rev
      2017;3:15-23. DOI: 10.1302/2058-5241.3.160089.

PMID- 29657842
TI  - Repair of syndesmosis injury in ankle fractures: Current state of the art.
AB  - Conventional treatment of syndesmosis injuries in rotationally unstable ankle
      fractures is associated with an unacceptably high rate of malreduction, and this
      has led to a paradigm shift in the approach to a newer concept of anatomical
      repair.In the anatomical approach, the principle is to 'directly fix what is
      broken and repair what is torn'. The approach is effective in reducing the rate
      of syndesmosis malreduction, increasing the biomechanical strength of syndesmosis
      fixation and avoiding the need for trans-syndesmotic fixation and its secondary
      removal.The objective of this review article is to compare the conventional
      treatment of these injuries (accepted usage, general consent, traditional,
      generally accepted) with a newer anatomical approach to be considered as a shift
      in thinking. Cite this article: EFORT Open Rev 2018;3:24-29. DOI: 10.1302/2058
      5241.3.170017.

PMID- 29657843
TI  - Impingement around the hip: beyond cam and pincer.
AB  - In this review, we bring to the attention of the reader three relatively unknown
      types of hip impingement. We explain the concept of low anterior inferior iliac
      spine (AIIS) impingement, also known as sub-spine impingement, ischio-femoral
      impingement (IFI) and pelvi-trochanteric impingement. For each type of
      impingement, we performed a search of relevant literature.We searched the PubMed,
      Medline (Ovid) and Embase databases from 1960 to March 2016. For each different
      type of impingement, a different search strategy was conducted.In total, 19
      studies were included and described. No data analysis was performed since there
      was not much comparable data between studies.An overview of symptoms, clinical
      tests and possible surgical treatment options for the three different types of
      extra-articular impingement is provided.Several disorders around the hip can
      cause similar complaints. Therefore, we plead for a standardized classification.
      In young and athletic patients, in particular, there is much to gain if hip
      impingement is diagnosed early. Cite this article: EFORT Open Rev 2018;3:30-38.
      DOI: 10.1302/2058-5241.3.160068.

PMID- 29657844
TI  - Spine-hip relations in patients with hip osteoarthritis.
AB  - Patients with hip osteoarthritis often have an abnormal spine-hip relation (SHR),
      meaning the presence of a clinically deleterious spine-hip and/or hip-spine
      syndrome.Definition of the individual SHR is ideally done using the EOS(r)
      imaging system or, if not available, with conventional lumbopelvic lateral
      radiographs.By pre-operatively screening patients with abnormal SHR, it is
      possible to refine total hip replacement (THR) surgical planning, which may
      improve outcomes.An important component of the concept of kinematically aligned
      total hip arthroplasty (KA THA) consists of defining the optimal acetabular cup
      design and orientation based on the assessment of an individual's SHR, and use of
      the transverse acetabular ligament to adjust the cup positioning.The Bordeaux
      classification might advance the understanding of SHR and hopefully help improve
      THR outcomes. Cite this article: EFORT Open Rev 2018;3:39-44. DOI: 10.1302/2058
      5241.3.170020.

PMID- 29657845
TI  - Long-term bone remodelling around 'legendary' cementless femoral stems.
AB  - Bone remodelling around a stem is an unavoidable long-term physiological process
      highly related to implant design. For some predisposed patients, it can lead to
      periprosthetic bone loss secondary to severe stress-shielding, which is thought
      to be detrimental by contributing to late loosening, late periprosthetic
      fracture, and thus rendering revision surgery more complicated.However, these
      concerns remain theoretical, since late loosening has yet to be documented among
      bone ingrowth cementless stems demonstrating periprosthetic bone loss associated
      with stress-shielding.Because none of the stems replicate the physiological load
      pattern on the proximal femur, each stem design is associated with a specific
      load pattern leading to specific adaptive periprosthetic bone remodelling. In
      their daily practice, orthopaedic surgeons need to differentiate physiological
      long-term bone remodelling patterns from pathological conditions such as
      loosening, sepsis or osteolysis.To aid in that process, we decided to clarify the
      behaviour of the five most used femoral stems. In order to provide translational
      knowledge, we decided to gather the designers' and experts' knowledge and
      experience related to the design rationale and the long-term bone remodelling of
      the following femoral stems we deemed 'legendary' and still commonly used: Corail
      (Depuy); Taperloc (Biomet); AML (Depuy); Alloclassic (Zimmer); and CLS-Spotorno
      (Zimmer). Cite this article: EFORT Open Rev 2018;3:45-57. DOI: 10.1302/2058
      5241.3.170024.

PMID- 29657847
TI  - Axillary nerve injury associated with glenohumeral dislocation: A review and
      algorithm for management.
AB  - Axillary nerve injury is a well-recognized complication of glenohumeral
      dislocation. It is often a low-grade injury which progresses to full recovery
      without intervention. There is, however, a small number of patients who have
      received a higher-grade injury and are less likely to achieve a functional
      recovery without surgical exploration and reconstruction.Following a review of
      the literature and consideration of local practice in a regional peripheral nerve
      injury unit, an algorithm has been developed to help identification of those
      patients with more severe nerve injuries.Early identification of patients with
      high-grade injuries allows rapid referral to peripheral nerve injury centres,
      allowing specialist observation or intervention at an early stage in their
      injury, thus aiming to maximize potential for recovery. Cite this article: EFORT
      Open Rev 2018;3:70-77. DOI:10.1302/2058-5241.3.170003.

PMID- 29657846
TI  - Reverse total shoulder arthroplasty.
AB  - Since the introduction of reverse total shoulder arthroplasty (RTSA) in 1987 (in
      Europe) and 2004 (in the United States), the number of RTSAs performed annually
      has increased.Although the main indication for RTSA has been rotator cuff tears,
      indications have expanded to include several shoulder conditions, many of which
      involve dysfunction of the rotator cuff.RTSA complications have been reported to
      affect 19% to 68% of patients and include acromial fracture, haematoma,
      infection, instability, mechanical baseplate failure, neurological injury,
      periprosthetic fracture and scapular notching.Current controversies in RTSA
      include optimal baseplate positioning, humeral neck-shaft angle (135 degrees 
      versus 155 degrees ), glenosphere placement (medial, lateral or bony increased
      offset RTSA) and subscapularis repair.Improvements in prosthesis design, surgeon
      experience and clinical results will need to occur to optimize this treatment for
      many shoulder conditions. Cite this article: EFORT Open Rev 2018;3:58-69 DOI:
      10.1302/2058-5241.3.170044.

PMID- 29657848
TI  - Medial subvastus versus the medial parapatellar approach for total knee
      replacement: A systematic review and meta-analysis of randomized controlled
      trials.
AB  - Twenty randomized controlled trials comprising 1893 primary total knee
      replacements were included in this review.The subvastus approach conferred
      superior results for mean difference (MD) in time to regain an active straight
      leg raise (1.7 days, 95% confidence interval [CI] 1.0 to 2.3), visual analogue
      score for pain on day one (0.8 points on a scale out of 10, 95% CI 0.2 to 1.4)
      and total range of knee movement at one week (7 degrees , 95% CI 3.2 to 10.7).
      The subvastus approach also resulted in fewer lateral releases (odds ratio 0.4,
      95% CI 0.2 to 0.7) and less peri-operative blood loss (MD 57 mL, 95% CI 10.5 to
      106.4) but prolonged surgical times (MD 9.7 min, 95% CI 3.9 to 15.6).There was no
      difference in Knee Society Score at six weeks or one year, or the rate of adverse
      events including superficial or deep infection, deep vein thrombosis or knee
      stiffness requiring manipulation under anaesthesia.This review demonstrates
      evidence of early post-operative benefits following the subvastus approach with
      equivalence between approaches thereafter. Cite this article: EFORT Open Rev
      2018;3:78-84. DOI: 10.1302/2058-5241.3.170030.

PMID- 29657849
TI  - Talar process fractures: An overview and update of the literature.
AB  - Fractures of the lateral and the posterior processes of the talus are uncommon
      and frequently missed because of a low level of suspicion and difficulty in
      interpretation on plain radiographs. Missed fractures can lead to persistent pain
      and reduced function.Lateral process fractures are usually a consequence of
      forced dorsiflexion and inversion of fixed pronated foot. These are also commonly
      known as snowboarder's fractures.The posterior process of the talus is composed
      of medial and lateral tubercles, separated by the groove for the flexor hallucis
      longus tendon.The usual mechanism of injury is forced hyperplantarflexion and
      inversion causing direct compression of the posterior talus, or an avulsion
      fracture caused by the posterior talofibular ligament. CT scans are helpful in
      cases of high clinical suspicion.There is a lack of consensus regarding optimal
      management of these fractures; however, management depends on the size, location
      and displacement of the fragment, the degree of cartilage damage and instability
      of the subtalar joint. Non-operative treatment includes immobilization and
      protected weight-bearing for six weeks. Surgical treatment includes open
      reduction and internal fixation or excision of the fragments, depending on the
      size.Fractures of the lateral and the posterior processes of the talus are
      uncommon but important injuries that may result in significant disability in
      cases of missed diagnosis or delayed or inadequate treatment. Early diagnosis and
      timely management of these fractures help to avoid long-term complications,
      including malunion, nonunion or severe subtalar joint osteoarthritis. Cite this
      article: EFORT Open Rev 2018;3:85-92. DOI: 10.1302/2058-5241.3.170040.

PMID- 29657850
TI  - Hamstring autograft size importance in anterior cruciate ligament repair surgery.
AB  - Graft size in hamstring autograft anterior cruciate ligament (ACL) surgery is an
      important factor directly related to failure. Most of the evidence in the field
      suggests that the size of the graft in hamstring autograft ACL reconstruction
      matters when the surgeon is trying to avoid failures.The exact graft diameter
      needed to avoid failures is not absolutely clear and could depend on other
      factors, but newer studies suggest than even increases of 0.5 mm up to a graft
      size of 10 mm are beneficial for the patient. There is still no evidence to
      recommend the use of grafts > 10 mm.Several methods - e.g. folding the graft in
      more strands - that are simple and reproducible have been published lately to
      address the problem of having an insufficient graft size when performing an ACL
      reconstruction. Due to the evidence presented, we think it is necessary for the
      surgeon to have them in his or her arsenal before performing an ACL
      reconstruction.There are obviously other factors that should be considered,
      especially age. Therefore, a larger graft size should not be taken as the only
      goal in ACL reconstruction. Cite this article: EFORT Open Rev 2018;3:93-97. DOI:
      10.1302/2058-5241.3.170038.

PMID- 29657851
TI  - Kinematic alignment technique for total hip and knee arthroplasty: The
      personalized implant positioning surgery.
AB  - Conventional techniques for hip and knee arthroplasty have led to good long-term
      clinical outcomes, but complications remain despite better surgical precision and
      improvements in implant design and quality.Technological improvements and a
      better understanding of joint kinematics have facilitated the progression to
      'personalized' implant positioning (kinematic alignment) for total hip (THA) and
      knee (TKA) arthroplasty, the true value of which remains to be determined.By
      achieving a true knee resurfacing, the kinematic alignment (KA) technique for TKA
      aims at aligning the components with the physiological kinematic axes of the knee
      and restoring the constitutional tibio-femoral joint line frontal and axial
      orientation and soft-tissue laxity.The KA technique for THA aims at restoring the
      native 'combined femoro-acetabular anteversion' and the hip's centre of rotation,
      and occasionally adjusting the cup position and design based on the assessment of
      the individual spine-hip relation.The key element for optimal prosthetic joint
      kinematics (hip or knee) is to reproduce the femoral anatomy.The transverse
      acetabular ligament (TAL) is the reference landmark to adjust the cup position.
      Cite this article: EFORT Open Rev 2018;3:98-105. DOI: 10.1302/2058-5241.3.170022.

PMID- 29657853
TI  - Training scientists as future industry leaders: teaching translational science
      from an industry executive's perspective.
AB  - PhDs and post-doctoral biomedical graduates, in greater numbers, are choosing
      industry based careers. However, most scientists do not have formal training in
      business strategies and venture creation and may find senior management positions
      untenable. To fill this training gap, "Biotechnology Industry: Structure and
      Strategy" was offered at New York University School of Medicine (NYUSOM). The
      course focuses on the business aspects of translational medicine and research
      translation and incorporates the practice of business case discussions, mock
      negotiation, and direct interactions into the didactic. The goal is to teach
      scientists at an early career stage how to create solutions, whether at the
      molecular level or via the creation of devices or software, to benefit those with
      disease. In doing so, young, talented scientists can develop a congruent mindset
      with biotechnology/industry executives. Our data demonstrates that the course
      enhances students' knowledge of the biotechnology industry. In turn, these
      learned skills may further encourage scientists to seek leadership positions in
      the field. Implementation of similar courses and educational programs will
      enhance scientists' training and inspire them to become innovative leaders in the
      discovery and development of therapeutics.

PMID- 29657854
TI  - Targeted drug discovery and development, from molecular signaling to the global
      market: an educational program at New York University, 5-year metrics.
AB  - Drug discovery and development (DDD) is a collaborative, dynamic process of great
      interest to researchers, but an area where there is a lack of formal training.
      The Drug Development Educational Program (DDEP) at New York University was
      created in 2012 to stimulate an improved, multidisciplinary DDD workforce by
      educating early stage scientists as well as a variety of other like-minded
      students. The first course of the program emphasizes post-compounding aspects of
      DDD; the second course focuses on molecular signaling pathways. In five years,
      196 students (candidates for PhD, MD, Master's degree, and post-doctoral MD/PhD)
      from different schools (Medicine, Biomedical Sciences, Dentistry, Engineering,
      Business, and Education) completed the course(s). Pre/post surveys demonstrate
      knowledge gain across all course topics. 26 students were granted career
      development awards (73% women, 23% underrepresented minorities). Some graduates
      of their respective degree-granting/post-doctoral programs embarked on DDD
      related careers. This program serves as a framework for other academic
      institutions to develop compatible programs designed to train a more informed DDD
      workforce.

PMID- 29657855
TI  - Developing sustainable research careers for KL2 scholars: The importance of an
      inclusive environment and mentorship.
AB  - Introduction: The National Clinical and Translational Science Award (CTSA)
      Consortium 2.0 has developed common metrics as a collaborative project for all
      participating sites. Metrics address several important aspects and functions of
      the consortium, including workforce development. The first workforce development
      metrics to be proposed for all CTSA hubs include the proportion of CTSA-supported
      trainees and scholars with sustainable careers in translational research and the
      diversity and inclusiveness of programs. Methods and results: The University of
      Utah Center for Clinical and Translational Science (CCTS), a CTSA hub, has been
      actively engaged in mentoring translational scientists for the last decade. We
      have developed programs, processes, and institutional policies that support
      translational scientists, which have resulted in 100% of our KL2 scholars
      remaining engaged in translational science and in increasing the inclusion of
      individuals under-represented in medicine in our research enterprise. In this
      paper, we share details of our program and what we believe are evidence-based
      best practices for developing sustainable translational research careers for all
      aspiring junior faculty members. Conclusions: The University of Utah Center for
      Clinical and Translational Science has been integral in catalyzing interactions
      across the campus to reverse the negative trends seen nationally in sustaining
      clinician scientists. Our programs and processes can serve as a model for other
      institutions seeking to develop translational scientists.

PMID- 29657852
TI  - Designing hydrogels for controlled drug delivery.
AB  - Hydrogel delivery systems can leverage therapeutically beneficial outcomes of
      drug delivery and have found clinical use. Hydrogels can provide spatial and
      temporal control over the release of various therapeutic agents, including small
      molecule drugs, macromolecular drugs and cells. Owing to their tunable physical
      properties, controllable degradability and capability to protect labile drugs
      from degradation, hydrogels serve as a platform in which various physiochemical
      interactions with the encapsulated drugs control their release. In this Review,
      we cover multiscale mechanisms underlying the design of hydrogel drug delivery
      systems, focusing on physical and chemical properties of the hydrogel network and
      the hydrogel-drug interactions across the network, mesh, and molecular (or
      atomistic) scales. We discuss how different mechanisms interact and can be
      integrated to exert fine control in time and space over the drug presentation. We
      also collect experimental release data from the literature, review clinical
      translation to date of these systems, and present quantitative comparisons
      between different systems to provide guidelines for the rational design of
      hydrogel delivery systems.

PMID- 29657856
TI  - Collaborative academic medical product development: An 8-year review of
      commercialization outcomes at the Institute of Translational Health Sciences.
AB  - Introduction: The Institute of Translational Health Sciences (ITHS), a Clinical
      and Translational Science Award (CTSA)-funded program at the University of
      Washington (UW), established the Drug and Device Advisory Committee (DDAC) to
      provide product-specific scientific and regulatory mentoring to investigators
      seeking to translate their discoveries into medical products. An 8-year
      retrospective analysis was undertaken to evaluate the impact of the DDAC programs
      on commercialization metrics. Methods: Tracked metrics included the number of
      teams who consulted with the DDAC, initiated a clinical trial, formed a startup,
      or were successful obtaining federal small business innovation awards or venture
      capital. The review includes historical comparisons of the startup rates for the
      UW School of Medicine and the Fred Hutchinson Cancer Research Center, two ITHS
      affiliated institutions that have had different DDAC utilization rates. Results:
      Between 2008 and 2016, the DDAC supported 161 unique project teams, 28% of which
      went on to form a startup. The commercialization rates for the UW School of
      Medicine increased significantly following integration of the DDAC into the
      commercialization programs offered by the UW technology transfer office.
      Conclusions: A formalized partnership between preclinical consulting and the
      technology transfer programs provides an efficient use of limited development
      funds and a more in-depth vetting of the business opportunity and regulatory path
      to development.

PMID- 29657857
TI  - The ASIBS Short Course: A unique strategy for increasing statistical competency
      of junior investigators in academic medicine.
AB  - As clinical researchers at academic medical institutions across the United States
      increasingly manage complex clinical databases and registries, they often lack
      the statistical expertise to utilize the data for research purposes. This
      statistical inadequacy prevents junior investigators from disseminating clinical
      findings in peer-reviewed journals and from obtaining research funding, thereby
      hindering their potential for promotion. Underrepresented minorities, in
      particular, confront unique challenges as clinical investigators stemming from a
      lack of methodologically rigorous research training in their graduate medical
      education. This creates a ripple effect for them with respect to acquiring full
      time appointments, obtaining federal research grants, and promotion to leadership
      positions in academic medicine. To fill this major gap in the statistical
      training of junior faculty and fellows, the authors developed the Applied
      Statistical Independence in Biological Systems (ASIBS) Short Course. The overall
      goal of ASIBS is to provide formal applied statistical training, via a hybrid
      distance and in-person learning format, to junior faculty and fellows actively
      involved in research at US academic medical institutions, with a special emphasis
      on underrepresented minorities. The authors present an overview of the design and
      implementation of ASIBS, along with a short-term evaluation of its impact for the
      first cohort of ASIBS participants.

PMID- 29657858
TI  - Adapting the buying funnel model of consumer behavior to the design of an online
      health research recruitment tool.
AB  - Introduction: UMHealthResearch is the University of Michigan's digital health
      research recruitment platform. It allows health researchers to connect
      efficiently with potentially eligible volunteers. Methods: In 2013, the
      UMHealthResearch team strategically adapted a consumer behavior model, the buying
      funnel, to create the Digital Health Research Participation Funnel. The Digital
      Health Research Participation Funnel was then used to design a more active way
      for potential participants to volunteer for research studies through
      UMHealthResearch. Results: In the 5 years before the redesign (2007-2012), an
      average of 1844 new accounts were created every year, whereas in the completed
      years after the redesign (2013-2016) the annual average improved to 3906, an
      increase of 111%. Conclusion: Although a randomized design was not possible in
      this instance, these preintervention and postintervention data suggest that the
      focus on user experience is an effective strategy for improving web-based
      research recruitment platforms.

PMID- 29657860
TI  - Toward a science of translational science.
AB  - Translational research as a discipline has experienced explosive growth over the
      last decade as evidenced by significant federal investment and the exponential
      increase in related publications. However, narrow project-focused or process
      based measurement approaches have resulted in insufficient techniques to measure
      the translational progress of institutions or large-scale networks. A shift from
      traditional industrial engineering approaches to systematic investigation using
      the techniques of scientometrics and network science will be required to assess
      the impact of investments in translational research.

PMID- 29657861
TI  - Assessing usefulness and researcher satisfaction with consent form templates.
AB  - Introduction: We aimed to improve the research consenting process by developing
      and evaluating simplified consent forms. Methods: Four templates written at the
      eighth-tenth grade reading level were developed and trialed by a group of experts
      in clinical research, health literacy, national regulatory requirements, and end
      users. Researchers from protocols which had received expedited review were
      surveyed at 2 time points regarding their use and assessment of the templates.
      Results: At baseline 18/86 (20.9%) responding researchers had heard of the
      templates and 5 (5.8%) reported that they had used them; 2 years later, 54.2%
      (32/59) had heard of the templates and 87.5% (28/32) had used them (p<0.001).
      Conclusions: Consent form templates may be one mechanism to improve patient
      comprehension of research protocols as well as efficiency of the review process,
      but require considerable time for development and implementation, and one key to
      their success is involvement and support from the IRB and technical staff.

PMID- 29657859
TI  - A survey of practices for the use of electronic health records to support
      research recruitment.
AB  - Electronic health records (EHRs) provide great promise for identifying cohorts
      and enhancing research recruitment. Such approaches are sorely needed, but there
      are few descriptions in the literature of prevailing practices to guide their
      use. A multidisciplinary workgroup was formed to examine current practices in the
      use of EHRs in recruitment and to propose future directions. The group surveyed
      consortium members regarding current practices. Over 98% of the Clinical and
      Translational Science Award Consortium responded to the survey. Brokered and self
      service data warehouse access are in early or full operation at 94% and 92% of
      institutions, respectively, whereas, EHR alerts to providers and to research
      teams are at 45% and 48%, respectively, and use of patient portals for research
      is at 20%. However, these percentages increase significantly to 88% and above if
      planning and exploratory work were considered cumulatively. For most approaches,
      implementation reflected perceived demand. Regulatory and workflow processes were
      similarly varied, and many respondents described substantive restrictions arising
      from logistical constraints and limitations on collaboration and data sharing.
      Survey results reflect wide variation in implementation and approach, and point
      to strong need for comparative research and development of best practices to
      protect patients and facilitate interinstitutional collaboration and multisite
      research.

PMID- 29657862
TI  - A review of social media methods and lessons learned from the National Children's
      Study.
AB  - Introduction: Given the reach and influence of social media, the National
      Children's Study Vanguard Study evaluated the feasibility, acceptability, and
      cost of using social media to support participant retention. Methods: We describe
      a social media experiment designed to assess the impact of social media on
      participant retention, discuss several key considerations for integrating social
      media into longitudinal research, and review factors that may influence
      engagement in research-related social media. Results: User participation varied
      but was most active when at launch. During the short life of the private online
      community, a total of 39 participants joined. General enthusiasm about the
      prospect of the online community was indicated. There were many lessons learned
      throughout the process in areas such as privacy, security, and Institutional
      Review Board clearance. These are described in detail. Conclusions: The
      opportunity to engage participants in longitudinal research using online social
      networks is enticing; however, more research is needed to consider the
      feasibility of their use in an ongoing manner. Recommendations are presented for
      future research seeking to use social media to improve retention in longitudinal
      research.

PMID- 29657863
TI  - Fluid resuscitation-associated increased mortality and inflammatory cytokine
      expression in murine polymicrobial sepsis.

PMID- 29657864
TI  - A Sequence-Dependent DNA Condensation Induced by Prion Protein.
AB  - Different studies indicated that the prion protein induces hybridization of
      complementary DNA strands. Cell culture studies showed that the scrapie isoform
      of prion protein remained bound with the chromosome. In present work, we used an
      oxazole dye, YOYO, as a reporter to quantitative characterization of the DNA
      condensation by prion protein. We observe that the prion protein induces greater
      fluorescence quenching of YOYO intercalated in DNA containing only GC bases
      compared to the DNA containing four bases whereas the effect of dye bound to DNA
      containing only AT bases is marginal. DNA-condensing biological polyamines are
      less effective than prion protein in quenching of DNA-bound YOYO fluorescence.
      The prion protein induces marginal quenching of fluorescence of the dye bound to
      oligonucleotides, which are resistant to condensation. The ultrastructural
      studies with electron microscope also validate the biophysical data. The GC bases
      of the target DNA are probably responsible for increased condensation in the
      presence of prion protein. To our knowledge, this is the first report of a human
      cellular protein inducing a sequence-dependent DNA condensation. The increased
      condensation of GC-rich DNA by prion protein may suggest a biological function of
      the prion protein and a role in its pathogenesis.

PMID- 29657865
TI  - Stress-Adaptive Responses Associated with High-Level Carbapenem Resistance in KPC
      Producing Klebsiella pneumoniae.
AB  - Carbapenem-resistant Enterobacteriaceae (CRE) organisms have emerged to become a
      major global public health threat among antimicrobial resistant bacterial human
      pathogens. Little is known about how CREs emerge. One characteristic phenotype of
      CREs is heteroresistance, which is clinically associated with treatment failure
      in patients given a carbapenem. Through in vitro whole-transcriptome analysis we
      tracked gene expression over time in two different strains (BR7, BR21) of
      heteroresistant KPC-producing Klebsiella pneumoniae, first exposed to a
      bactericidal concentration of imipenem followed by growth in drug-free medium. In
      both strains, the immediate response was dominated by a shift in expression of
      genes involved in glycolysis toward those involved in catabolic pathways. This
      response was followed by global dampening of transcriptional changes involving
      protein translation, folding and transport, and decreased expression of genes
      encoding critical junctures of lipopolysaccharide biosynthesis. The emerged high
      level carbapenem-resistant BR21 subpopulation had a prophage (IS1) disrupting
      ompK36 associated with irreversible OmpK36 porin loss. On the other hand, OmpK36
      loss in BR7 was reversible. The acquisition of high-level carbapenem resistance
      by the two heteroresistant strains was associated with distinct and shared
      stepwise transcriptional programs. Carbapenem heteroresistance may emerge from
      the most adaptive subpopulation among a population of cells undergoing a complex
      set of stress-adaptive responses.

PMID- 29657866
TI  - Portable lensless wide-field microscopy imaging platform based on digital inline
      holography and multi-frame pixel super-resolution.
AB  - In this paper, an irregular displacement-based lensless wide-field microscopy
      imaging platform is presented by combining digital in-line holography and
      computational pixel super-resolution using multi-frame processing. The samples
      are illuminated by a nearly coherent illumination system, where the hologram
      shadows are projected into a complementary metal-oxide semiconductor-based
      imaging sensor. To increase the resolution, a multi-frame pixel resolution
      approach is employed to produce a single holographic image from multiple frame
      observations of the scene, with small planar displacements. Displacements are
      resolved by a hybrid approach: (i) alignment of the LR images by a fast feature
      based registration method, and (ii) fine adjustment of the sub-pixel information
      using a continuous optimization approach designed to find the global optimum
      solution. Numerical method for phase-retrieval is applied to decode the signal
      and reconstruct the morphological details of the analyzed sample. The presented
      approach was evaluated with various biological samples including sperm and
      platelets, whose dimensions are in the order of a few microns. The obtained
      results demonstrate a spatial resolution of 1.55 um on a field-of-view of ~30
      mm2.

PMID- 29657867
TI  - The relationship of serum endocan levels and anti-TNF-alpha therapy in patients
      with ankylosing spondylitis.
AB  - Objective: Endocan is a marker for vascular pathogenesis and important mediator
      of angiogenesis that strongly associates with inflammation and vascular diseases.
      Growing evidence suggest that inflammatory cytokine tumor necrosis factor (TNF
      alpha) plays a role in its regulation and secretion, whereas TNF-alpha inhibitors
      may have the opposite influence. The aim of this research is to investigate the
      association between serum endocan and anti-TNF-alpha drug treatment in patients
      with ankylosing spondylitis (AS). Methods: Serum endocan levels were analyzed in
      42 patients with AS under anti-TNF-alpha usage. Control group consisted of 37
      patients with AS who are not receiving anti-TNF drugs. Endocan is analyzed using
      ESM-1 ELISA kits. The blood glucose and lipid measurements of patients were also
      assessed. Results: There was no significant change in serum endocan levels among
      groups. The total cholesterol, triglyceride, and LDL-C levels were higher in
      patients receiving anti-TNF-alpha; however, differences were not significant.
      There was no significant correlation between serum endocan levels and blood lipid
      measurements. Conclusion: Anti-TNF-alpha treatment does not affect serum endocan
      levels in patients with AS. This research has been first to evaluate the
      relationship between serum endocan and anti-TNF-alpha therapy in AS. Future
      studies are necessary to verify the exact role of anti-TNF-alpha therapy on serum
      endocan levels in patients with AS.

PMID- 29657868
TI  - Outcomes of hydralazine induced renal vasculitis.
AB  - Objective: Hydralazine has been implicated as an etiologic agent for lupus-like
      syndrome and vasculitis. Hydralazine-induced vasculitis frequently affects the
      kidney, but the long-term renal outcomes in these patients have not yet been
      studied. Methods: Patients who had a diagnosis of ANCA-associated vasculitis
      (AAV) and were on hydralazine at the time of AAV diagnosis were included in this
      retrospective cohort study. Clinical and laboratory data were obtained from the
      review of medical records. Results: Seven patients met the criteria for
      hydralazine-induced AAV. Five patients (71%) were African-American and four (57%)
      were female. The median age was 69 years at the time of diagnosis. All patients
      had renal involvement with two of them showing lung involvement as well. All
      patients had positive MPO antibody and one patient had positive PR3 antibody. ANA
      was positive in all patients, and three of seven patients had positive anti
      histone antibody. All of them were treated with immunosuppression and withdrawal
      of hydralazine. Three patients reached end-stage renal disease. The median follow
      up time was 13 months. Conclusion: Renal involvement in hydralazine-induced AAV
      was universal and can be associated with a poor renal outcome despite
      immunosuppressive therapy.

PMID- 29657869
TI  - Impaired cardiac and vascular motion in patients with Takayasu's arteritis: A
      velocity vector imaging-based study.
AB  - Objective: Takayasu's arteritis (TAK) is a chronic inflammatory vasculitis of the
      aorta and its major branches. In the present study, we aimed to evaluate the
      motion of the vascular wall and myocardial contractility by using a novel strain
      imaging method, velocity vector imaging (VVI), in patients with TAK. We also
      aimed to compare them with another inflammatory autoimmune disorder, systemic
      lupus erythematosus (SLE). Methods: We studied 33 patients with TAK, 18 patients
      with SLE, and 20 age- and sex-matched controls. All participants were subjected
      to carotid artery Doppler ultrasonography and transthoracic echocardiographic
      evaluation. VVI analysis was also performed to assess subclinical left
      ventricular (LV) systolic dysfunction and to determine tissue motion of the
      common carotid arteries (CCAs). Results: Aortic strain and distensibility were
      significantly impaired in patients with TAK, while the aortic stiffness and
      carotid artery stiffness indexes were increased. Aortic distensibility was the
      only parameter that was decreased among SLE patients. The values of CCA peak
      longitudinal strain, strain rate, and total longitudinal displacement (TLD) were
      also impaired in patients with TAK. Peak radial velocity was decreased while time
      to-peak radial velocity was increased. In the SLE group, peak longitudinal
      strain, strain rate, TLD, and peak radial velocity were impaired. LV longitudinal
      peak systolic strain and strain rate were reduced in patients with TAK.
      Similarly, we revealed impaired subclinical LV systolic function in patients with
      SLE. Conclusion: VVI is a novel strain imaging technique with additional value to
      determine early impairment in vascular and myocardial wall motion in patients
      with TAK.

PMID- 29657870
TI  - Is the serum oxytocin level altered by treatment in rheumatoid arthritis patients
      complicated with depression?
AB  - Objective: The objective of this study was to investigate the factors associated
      with depression, including serum oxytocin (OXT) levels, disease activity,
      activities of daily living (ADL), and quality of life (QOL), and their effects on
      rheumatoid arthritis (RA). Methods: This study included 42 RA patients who
      received treatment with a biological agent. We measured the following variables
      before and after 6 months of treatment: baseline characteristics, including age,
      sex, disease duration, smoking, and body mass index (BMI); prednisolone and
      methotrexate dose; serum level of matrix metalloproteinase-3 (MMP-3); erythrocyte
      sedimentation rate (ESR); and C-reactive protein (CRP) level. The disease
      activity of RA was assessed using the Simplified Disease Activity Index (SDAI);
      depression was assessed using the Hamilton Depression Rating Scale (HAM-D); ADL
      was assessed using the Health Assessment Questionnaire; and QOL was assessed
      using the Short Form (SF)-36. Serum OXT levels were determined using enzyme
      linked immunosorbent assay. Results: The HAM-D score significantly correlated
      with the SDAI, and the mental component summary (MCS) score of SF-36. However,
      the serum OXT levels did not correlate with the HAM-D score. Regression analysis
      using the HAM-D score as the objective variable identified female sex, smoking,
      BMI, and all the three component scores of SF-36, but not serum OXT levels, as
      significant factors. Comparisons between before and after treatment showed that
      the HAM-D score improved from 5 to 1.5; however, the serum OXT levels did not
      change. Conclusion: The variables of female sex, smoking, BMI, and QOL correlated
      with depression complicated with RA. However, serum OXT levels did not correlate
      directly.

PMID- 29657871
TI  - Investigation of the role of interleukin-1 receptor antagonist VNTR variant on
      the Behcet's disease.
AB  - Objective: Behcet's disease (BD), a chronic multisystem inflammatory disorder, is
      mainly characterized by relapsing periods of a wide range of clinical symptoms.
      Several cytokine genes may play important roles in the pathogenesis of BD.
      Therefore, interleukin-1 receptor antagonist (IL-1Ra) gene 86bp variable number
      tandem repeat (VNTR) variant was investigated in patients with BD in a Turkish
      population. Methods: One hundred nine patients (60 females, 49 males; the mean
      age+/-standard deviation [SD] was 36.56+/-9.571 years) with BD and one hundred
      healthy individuals (54 females, 46 males; the mean age+/-SD was 36.64+/-2.294
      years) were examined in the study. For genotyping, polymerase chain reaction
      restriction fragment length polymorphism analysis was employed. Data were
      analyzed using Statistical Package for Social Sciences (SPSS) 22.0 (IBM Corp.;
      Armonk, NY, USA) (p<0.05). Results: The genotype distribution and allele
      frequencies of the IL-1Ra VNTR variant did not differ significantly between the
      patients and the controls (p>0.05). The frequency of the a1/a1, a1/a2 genotypes
      and a1, a2 alleles were the most common both in patients and healthy controls
      (p=0.37, p=0.26, and p=0.53, respectively). Also, no statistically significant
      difference was found between the IL-1Ra VNTR variant genotypes and clinical
      characteristics (p>0.05). Conclusion: The results of this study do not support an
      association between the IL-1Ra VNTR variant and the risk of BD in a Turkish
      population. However, further studies of this variant with larger sample sizes and
      different ethnicities are required for confirmation.

PMID- 29657872
TI  - Therapeutic plasma exchange for refractory SLE: A comparison of outcomes between
      different sub-phenotypes.
AB  - Objective: Therapeutic plasma exchange (TPE) offers an alternative therapeutic
      modality for patients with systemic lupus erythematosus (SLE) and primary
      antiphospholipid syndrome (APS). However, there is conflicting evidence regarding
      its efficacy in different sub-phenotypes. This study aimed to investigate the
      main clinical characteristics and outcomes of patients with different phenotypes
      of SLE and APS treated with TPE at a tertiary care center. Methods: The database
      of the Blood and Apheresis Unit between 2001 and 2013 was screened for patients
      with SLE and primary APS. SLE disease activity index (SELENA-SLEDAI), the
      indications for treatment, complications, and outcomes were obtained from a
      review of medical records and phone calls. A total of 24 patients (SLE: 20, APS:
      4) were recruited for the study. Results: Mean ages of SLE (M/F: 1/19) and
      primary APS (PAPS) patients (M/F: 2/2) were 32.4+/-12.89 and 52.0+/-10.7 years,
      respectively. The main indications for TPE were hematologic, neurologic, and
      pulmonary involvement and APS-related symptoms. TPE was preferred in eight
      patients because of leucopenia and co-infection. SLEDAI was significantly
      decreased after TPE (16.7+/-8.3 before vs. 8.8+/-3.1 after, p=0.001). Both
      primary APS and SLE-related catastrophic APS (CAPS) patients had completely
      responded to TPE. The success rate of TPE in patients with thrombocytopenia was
      lower than patients with hemolytic anemia. The median (IQR 25%-75%) number of TPE
      sessions was 6.5 (5-10.5). In total, five patients experienced TPE-related major
      adverse events (catheter infections in three patients, bleeding in one patient,
      and hypotension in one patient). The median (IQR 25%-75%) follow-up time was 33.5
      (6.75-81.25) months. In total, four patients died during follow up, of which
      three died during the period of TPE administration. Conclusion: Our data suggest
      that CAPS and other APS-related problems respond well to the TPE treatment. TPE
      should be kept in mind for the treatment of patients with other features of SLE,
      especially those resistant to other agents and in the presence of leucopenia.

PMID- 29657873
TI  - Neuropathic pain in pregnant Turkish women with lumbopelvic pain and its impact
      on health-related quality of life.
AB  - Objectives: To investigate the prevalence of neuropathic pain in pregnant women
      and to state its influence on the functional status and health-related quality of
      life (HRQoL) in terms of physical, social, and emotional functioning. Methods: A
      total of 90 pregnant women with lumbopelvic pain (LPP) and non-pregnant and
      healthy controls were included. The presence of neuropathic pain was determined
      using the Leeds assessment of neuropathic symptoms and signs (LANNS)
      questionnaire. The HRQoL was assessed using the Nottingham Health Profile (NHP),
      and the functional status was evaluated using the Oswestry Disability Index
      (ODI). The severity of pain was measured using a visual analog scale. Results:
      The LANNS score was >=12 in 34 pregnant women (37.8%). The prevalence of
      neuropathic pain was higher in pregnant women with LPP (odds ratio=6.22; 95%
      confidence interval=2.68-14.44) (p<0.001) than in controls. The LANNS score was
      found to be correlated with the physical mobility subgroup in the NHP at high
      levels (p=0.002, r=0.32) and with the ODI and pain subgroup in the NHP at
      moderate levels (p=0.013, r=0.26 and p=0.038, r=0.22, respectively). Conclusion:
      The present study is the first to demonstrate that neuropathic pain is associated
      with pregnancy-related LPP and strongly correlated with functional impairment and
      deterioration in the HRQoL. A better understanding of neuropathic pain mechanisms
      in pregnancy-related LPP will help us find more effective treatment strategies.

PMID- 29657874
TI  - The reliability and validity of the Turkish version of the Fibromyalgia
      Participation Questionnaire.
AB  - Objective: The objective of this study was to test the reliability and validity
      of the Turkish version of the Fibromyalgia Participation Questionnaire (FPQ).
      Methods: One hundred and eighty-four female patients with fibromyalgia syndrome
      were included in the study. All patients filled out the Turkish FPQ (FPQ-T)
      questionnaire, which was obtained by translation from German according to the
      guideline for the process of cross-cultural adaptation The patients filled out
      the revised Fibromyalgia Impact Questionnaire (FIQ) and reevaluated the FPQ-T two
      hours later. Internal consistency reliability of the FPQ-T was assessed by
      calculating the "if item deleted" using Cronbach's alpha and the "item-total
      correction" coefficient for each item of the questionnaire. The consistency of
      the subscales and the correlation of the test-retest values were assessed. The
      test-retest values were compared using the Wilcoxon test. Criterion validity was
      measured using FIQ scales by Spearman's rank correlation coefficient. Results:
      For internal reliability, Cronbach's alpha coefficient was calculated as 0.957
      for nonworking patients and 0.958 for working patients. Cronbach's alpha values
      of 0.939, 0.871, and 0.914 were obtained for daily, social, and work life,
      respectively. Correlation coefficients were 0.888 for daily life, 0.859 for
      social life, and 0.901 overall in the nonworking group versus 0.896 the in
      working group. The comparison of scores obtained from test-retest measurements
      showed no significant difference except for Item 3. The correlation of the
      symptom severity score (SSS) and the FPQ-T was r=0.385 (p<0.001) and r=0.390
      (p<0.001) for the nonworking and working subgroups, respectively. The evaluation
      of construct validity showed a significant correlation between the SSS and FPQ-T.
      Conclusion: The results of our study showed that the FPQ-T is reliable and valid
      for assessing participation and social functioning in fibromyalgia patients in
      Turkish society.

PMID- 29657875
TI  - Relationship between diet and ankylosing spondylitis: A systematic review.
AB  - The question of whether diet plays a role in the onset of ankylosing spondylitis
      (AS) or can affect the course of the disease is an important one for many
      patients and healthcare providers. The aims of this study were to investigate
      whether: 1) patients with AS report different diets to those without AS; 2)
      amongst patients with AS, diet is related to severity; 3) persons with particular
      diets are less likely to develop AS; 4) specific dietary interventions improve
      the AS symptoms. The review was conducted according to the Preferred Reporting
      Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Medline,
      Embase, Cochrane Library, and reference lists of relevant articles were searched.
      Two authors independently selected eligible studies, assessed the quality of
      included trials, and extracted the data. Sixteen studies (nine observational and
      seven interventions) were included in the review. Due to the heterogeneity of the
      study designs and analyses, the results could not be aggregated. Evidence on a
      possible relationship between AS and diet is extremely limited and inconclusive
      due to the majority of included studies being small, single studies with moderate
      to-high risk of bias, and insufficient reporting of results.

PMID- 29657876
TI  - Magnesium disorders can cause calcium pyrophosphate deposition disease: A case
      report and literature review.
AB  - Calcium pyrophosphate deposition (CPPD) disease, also known as pseudogout, is one
      of the most common forms of inflammatory arthritis. A variety of comorbidities
      and metabolic conditions have been recognized to predispose to CPPD. We describe
      here a patient with chronic CPP arthritis due to hypomagnesemia, which is one of
      the metabolic etiologies associated with CPPD, especially in younger patients. We
      also performed a literature search and reviewed all reported cases of CPPD
      disease associated with hypomagnesemia. All cases of hypomagnesemia and its
      etiologies leading to CPP arthropathy identified in the literature by this
      systematic search are summarized in this paper.

PMID- 29657877
TI  - Semaphorin3A: A potential therapeutic tool in immune-mediated diseases.
AB  - The significance of semaphorin3A (sema3A) in regulating immune-mediated
      inflammation is widely reported. There are multiple mechanisms involved in the
      process of sema3A-mediated regulation. One of them is the ability of sema3A to
      maintain a sufficient regulation of both T-cell and B-cell activation. Because it
      is involved in the pathogenesis of many autoimmune, infectious, and malignant
      diseases, sema3A turns to be a promising therapeutic tool to be studied and
      applied in these diseases.

PMID- 29657878
TI  - A clinical threat in patients with granulomatosis polyangiitis in remission:
      Subglottic stenosis.
AB  - Granulomatosis with polyangiitis (GPA) is a systemic necrotizing granulomatous
      disease that involves small- and medium-sized arteries and affects the main
      respiratory tracts and kidneys. Upper respiratory tract involvement usually
      occurs in 90% of patients, who most frequently present with symptoms of chronic
      sinusitis. Subglottic stenosis (SS) is a rare and severe complication that is
      usually observed in approximately 15% of patients. Here we present a case of SS
      in a patient with limited form of GPA during remission.

PMID- 29657879
TI  - Primary hyperparathyroidism and Gougerot disease.
AB  - Primary hyperparathyroidism (PHPT) is a common endocrine disorder caused by the
      overactivation of the parathyroid glands due to the autonomous production of the
      parathyroid hormone (PTH). The resultant hypercalcemia leads to a myriad of
      symptoms. Here we report the case of a 54-year-old female with a previous
      diagnosis of Gougerot disease, in whom clinical (diffuse bone pain, asthenia
      polydipsia, and polyuria) and laboratory features (calcium level, 3.1 mmol/L;
      phosphate level, 0.55 mmol/L; alkaline phosphatase level, 70 U/L; and intact PTH
      level, 1028.9 pmol/L) prompted the diagnosis of PHPT caused by a parathyroid
      adenoma as confirmed by anatomopathology. After treatment with renal replacement
      therapy, intravenous fluids and zolendronic acid, and subtotal parathyroidectomy,
      the patient status improved, with normal laboratory tests. However, the
      fortuitous nature of the association between Gougerot disease and PHPT as well as
      the physiopathological links between these two diseases remain to be specified.

PMID- 29657880
TI  - Pulmonary aspergillosis after treatment with infliximab in Still's disease and a
      literature review of Still's disease and pulmonary aspergillosis.
AB  - The use of anti-tumor necrosis factor alpha (anti-TNF-alpha) agents has increased
      during the past decade in rheumatology practice. Opportunistic infections have
      been reported with anti-TNF-alpha agents in clinical trials and post-marketing
      usage. Aspergillus infection is a rare opportunistic infection that is associated
      with immunosuppression, and there are reported cases of pulmonary aspergillosis
      in various rheumatic diseases treated with anti-TNF-alpha agents. Here, we
      present the first case of pulmonary aspergillosis associated with infliximab
      treatment in a patient with Still's disease.

PMID- 29657881
TI  - Visceral Leishmaniasis in the Mediterranean area.

PMID- 29657882
TI  - Perianal skin peeling: An important clinical pointer toward Kawasaki disease.

PMID- 29657883
TI  - Tropical pyomyositis caused by Klebsiella pneumoniae with rheumatoid arthritis.

PMID- 29657884
TI  - Ultra-Rapid Crystallization of L-alanine Using Monomode Microwaves, Indium Tin
      Oxide and Metal-Assisted and Microwave-Accelerated Evaporative Crystallization.
AB  - The use of indium tin oxide (ITO) and focused monomode microwave heating for the
      ultra-rapid crystallization of L-alanine (a model amino acid) is reported.
      Commercially available ITO dots (< 5 mm) attached to blank
      poly(methyl)methacrylate (PMMA, 5 cm in diameter with 21-well silicon isolators:
      referred to as the iCrystal plates) were found to withstand prolonged microwave
      heating during crystallization experiments. Crystallization of L-alanine was
      performed at room temperature (a control experiment), with the use of two
      microwave sources: a 2.45 GHz conventional microwave (900 W, power level 1, a
      control experiment) and 8 GHz (20 W) solid state, monomode microwave source with
      an applicator tip that focuses the microwave field to a 5-mm cavity. Initial
      appearance of L-alanine crystals and on iCrystal plates with ITO dots took 47 +/-
      2.9 min, 12 +/- 7.6 min and 1.5 +/- 0.5 min at room temperature, using a
      conventional microwave and focused monomode microwave heating, respectively.
      Complete evaporation of the solvent using the focused microwaves was achieved in
      3.2 +/- 0.5 min, which is ~52-fold and ~172-fold faster than that observed at
      room temperature and using conventional microwave heating, respectively. The size
      and number of L-alanine crystals was dependent on the type of the 21-well
      iCrystal plates and the microwave heating method: 33 crystals of 585 +/- 137 MUm
      in size at room temperature > 37 crystals of 542 +/- 100 MUm in size with
      conventional microwave heating > 331 crystals of 311 +/- 190 MUm in size with
      focused monomode microwave. FTIR, optical microscopy and powder X-ray diffraction
      analysis showed that the chemical composition and crystallinity of the L-alanine
      crystals did not change when exposed to microwave heating and ITO surfaces. In
      addition, theoretical simulations for the binding of L-alanine molecules to ITO
      and other metals showed the predicted nature of hydrogen bonds formed between L
      alanine and these surfaces.

PMID- 29657885
TI  - First Step to Success: Applications to Preschoolers at Risk of Developing Autism
      Spectrum Disorders.
AB  - Preschool children with Autism Spectrum Disorder (ASD) may not always be
      recognized as such during their early years, but some of their behavioral
      problems may nonetheless prompt a referral for behavioral intervention. Whether
      such an intervention brings any benefit has not been well studied. We identified
      a subsample of 34 preschool children at risk for autism spectrum disorder from a
      large randomized controlled trial (N = 126) of the First Step to Success program.
      Children at risk of developing ASD demonstrated significant improvements on seven
      of 11 outcome measures and on a responder analyses based on symptom severity.
      Process and fidelity measures also suggested that First Step was both feasible
      and socially acceptable. Implications for early intervention for children at risk
      of developing ASD are discussed.

PMID- 29657886
TI  - Spectroscopic Investigation of the Electrosynthesis of Diphenyl Carbonate from CO
      and Phenol on Gold Electrodes.
AB  - In this work, we study the synthesis of diphenyl carbonate (DPC) from phenol and
      CO on gold electrodes studied by means of in situ Fourier transform infrared
      spectroscopy (FTIR). The results show that, on gold electrodes, the formation of
      DPC is observed at potentials as low as 0.4 V vs Ag/AgCl, together with the
      formation of dimethyl carbonate (DMC) from the carbonylation of methanol that was
      used as a solvent. The spectroelectrochemical results also suggest that the
      formation of DPC occurs via the replacement of the methoxy groups from DMC with
      phenoxy groups from phenol and not directly by the carbonylation of phenol.
      Although this transesterification process is known to occur with heterogeneous
      catalysts, it has not been reported under electrochemical conditions. These are
      interesting findings, since the direct DPC production by carbonylation of phenol
      to DPC is usually performed with Pd-based catalysts. With this reaction scheme of
      transesterification happening under electrochemical conditions, other non-Pd
      catalysts could be used as well for one-step DPC production from phenol and CO.
      These findings give important mechanistic insights into this reaction and open up
      possibilities to an alternative process for the production of DPC.

PMID- 29657888
TI  - Personal perspectives on the evolution of radiation therapy and future outlook
      for SRS.

PMID- 29657887
TI  - Supramolecular Approaches To Control Activity and Selectivity in Hydroformylation
      Catalysis.
AB  - The hydroformylation reaction is one of the most intensively explored reactions
      in the field of homogeneous transition metal catalysis, and many industrial
      applications are known. However, this atom economical reaction has not been used
      to its full potential, as many selectivity issues have not been solved.
      Traditionally, the selectivity is controlled by the ligand that is coordinated to
      the active metal center. Recently, supramolecular strategies have been
      demonstrated to provide powerful complementary tools to control activity and
      selectivity in hydroformylation reactions. In this review, we will highlight
      these supramolecular strategies. We have organized this paper in sections in
      which we describe the use of supramolecular bidentate ligands, substrate
      preorganization by interactions between the substrate and functional groups of
      the ligands, and hydroformylation catalysis in molecular cages.

PMID- 29657889
TI  - Pre-operative versus post-operative radiosurgery for brain metastasis: Effects on
      treatment volume and inter-observer variability.
AB  - Purpose/Objectives: Compared to post-operative whole brain radiotherapy,
      resection cavity radiosurgery reduces impact on neuro-cognitive function and
      improves quality-of-life. However, coverage of the operative tract, in addition
      to tumour bed, may lead to large treatment volumes and inter-observer
      variability. We hypothesized that pre-operative radiosurgery reduces target
      volume size and inter-observer variability compared to post-operative
      radiosurgery. Materials/Methods: We identified 10 consecutive patients, with
      solitary brain metastasis, treated with post-operative cavity radiosurgery.Pre-
      and post-operative axial T1 contrast MRI were co-registered with the planning CT
      scans. Three radiation oncologists independently contoured the target volumes on
      the pre- and post-operative imaging. A 2mm-PTV margin was utilized for both
      strategies and radiosurgery treatment plans were generated. The following
      parameters were evaluated in the 2 plans: Mean target volume (cc), 50% isodose
      volume (cc), Inter-observer variability (Jaccard Index JI) and Conformity Index
      (CI). Results: There was no significant difference in the mean target volume, nor
      50% isodose volume, between pre- and post-operative strategies. (17.6 (95% CI
      9.98 - 25.22) versus 19.4 (95% CI 10.11 - 28.69) cc, P=0.80; 61.7 (95% CI 38.4 -
      85.0) vs 77.7 (95% CI 34.94 - 120.46) cc, P=0.65). There was significantly less
      inter-observer variability and improved conformity in the pre-operative group
      (Mean JI 0.84(95% CI 0.82 - 0.86) versus 0.70 (95% CI 0.62 - 0.78), P = 0.005;
      Mean CI 1.32 (95% CI 1.26 - 1.38) vs 1.45 (95% CI 1.36 - 1.54), P= 0.01). Planned
      subgroup analysis did not reveal any significant difference (between pre- vs post
      op) in the mean volume of cystic versus non-cystic metastasis. Deep lesions
      (>2.5cm from dura) had a larger post-operative target volume (25.8 (95% CI 15.1 -
      36.5) vs 12.3 (95% CI 6.54 - 18.06) cc, P=0.06) compared to superficial lesions.
      Conclusion: Pre-operative radiosurgery has less inter-observer variability and
      improved plan conformity. However, there was no difference in mean target volume
      between the pre- versus post-operative radiation. Contouring guidelines, and peer
      review, may help to reduce inter-observer variability for cavity radiosurgery.

PMID- 29657890
TI  - Pain flare after stereotactic radiosurgery for spine metastases.
AB  - Purpose: Understanding of pain flare (PF) following spine stereotactic
      radiosurgery (sSRS) is lacking. This study sought to determine the incidence and
      risk factors associated with PF following single fraction sSRS.
      Materials/methods: An IRB-approved database was compiled to include patients who
      underwent sSRS. Patient and disease characteristics as well as treatment and
      dosimetric details were collected retrospectively. Pain relief post-sSRS was
      prospectively collected using the Brief Pain Inventory (BPI). These factors were
      correlated to the development of PF (defined as an increase in pain within 7 days
      of treatment which resolved with steroids). Survival was calculated using Kaplan
      Meier analysis and logistic regression was utilized to evaluate the association
      between the clinical and treatment factors and occurrence of PF. Results: A total
      of 348 patients with 507 treatments were included. Median age and prescription
      dose were 59 years and 15 Gy (range: 7-18), respectively, and 62% of patients
      were male. Renal cell carcinoma (24%), lung cancer (14%), and breast cancer (11%)
      were the most common histologies, and 74% had epidural disease and 43% had thecal
      sac compression. The most common location of metastases was in the
      cervical/thoracic spine (59%), followed by lumbar spine (32%), and sacral spine
      (9%). Most common reason for treatment was pain (73%), followed by pain and
      neurological deficit (13%), asymptomatic disease (10%), and neurologic deficit
      only (3%). Median time to pain relief was 1.8 months. Median overall survival,
      time to radiographic failure, and time to pain progression were 13.6 months, 26.5
      months, and 56.6 months, respectively. Only 14.4% of treatments resulted in the
      development of PF. Univariate analysis showed that higher Karnofsky performance
      score (KPS) (OR=1.03, p=0.03), female gender (OR=1.80, p=0.02), higher
      prescription dose (OR=1.30, p=0.008), and tumor location of cervical/thoracic
      spine vs lumbar spine (OR=1.81, p=0.047) were predictors for the development of
      PF. On multivariate analysis, higher consult KPS (OR=1.03, p=0.04), female gender
      (OR=1.93, p=0.01), higher prescription dose (OR=1.27, p=0.02), and tumor location
      of cervical/thoracic spine vs lumbar spine (OR=1.81, p=0.05) remained predictors
      of PF. No other dosimetric parameters were associated with the development of PF.
      Conclusion: PF is an infrequent complication of sSRS. Predictors for the
      development of PF include higher consult KPS, female gender, higher prescription
      dose, and cervical/thoracic tumor location. Dose to the spinal cord was not a
      predictor of PF. Since a minority (14.4%) of treatments result in PF, we do not
      routinely utilize prophylactic steroid treatment; however, prophylactic steroids
      may be considered in female patients with cervical/thoracic metastases receiving
      higher dose sSRS.

PMID- 29657891
TI  - Stereotactic radiosurgery for primary tumors of the spine and spinal cord?.
AB  - Purpose: The purpose of this study was to evaluate the role of stereotactic
      radiosurgery in the treatment of primary tumors of the spine and spinal cord.
      Methods: An Institutional Review Board approved retrospective analysis of 30
      patients with primary spine tumors treated at a single institution was performed.
      Post-treatment pain, neurological, and radiographic responses were the endpoints.
      Results: Nine patients were treated for benign tumors, and 21 patients were
      treated for malignant tumors. The median dose delivered was 16 Gy in one
      fraction. Median follow up was 13.13 months (range, 1 month-84 months). Pain
      relief was 88% initially. Pain recurred in five patients with a median time to
      recurrence of 5 months (range, 3.6 months - 80 months). Neurological improvement
      was achieved in 65% of patients. Three patients experienced a recurrence in their
      neurological deficit (at 3.6 months, 1.6 years, and 3.7 years after SRS).
      Radiographic control was achieved in 77% of sites treated with SRS. Thirteen of
      the treated sites recurred with a median time of 9.9 months. Two long-term
      toxicities were observed (asymptomatic radio-necrosis of the erector spinae
      muscle and foot drop). Conclusions: Our results suggest that SRS is a safe and
      effective treatment option for primary tumors of the spine and spinal cord.

PMID- 29657892
TI  - Inversion recovery sequences improve delineation of optic pathways in the
      proximity of suprasellar lesions.
AB  - Introduction: In Gamma Knife Radiosurgery (GKRS) of suprasellar lesions, the
      exact localization of the visual pathways is important to avoid radiation induced
      optic neuropathy (RION). Reliable identification of the optic nerve, chiasm and
      tracts can be challenging using routine magnetic resonance imaging, especially in
      patients with lesions compressing the optic structures or in patients who had
      prior operation of suprasellar tumors. This study investigates the application of
      inversion recovery sequences (Fast gray and white matter acquisition T1 inversion
      recovery, FGATIR) to improve identification of the optic pathway. Methods:
      Inversion recovery sequences were performed on 5 healthy volunteers, varying
      their inversion times between 400 and 500 ms, and between 800 and 1100 ms.
      Inversion times were optimized to either suppress or to preserve the signal of
      the optic structures, while increasing or suppressing the signal of processes
      within the surrounding cisterns. Inversion recovery sequences were performed
      before radiosurgery on 10 patients with suprasellar tumors that were compressing
      or displacing the optic structures. Signal intensities of gray and white matter,
      of CSF and tumors were measured and subtraction images were calculated. Results:
      Compared to a standard T1-weighted sequence, delineation of the visual pathways
      was superior on inversion recovery images, both on images with suppression of the
      optic structures as well on images with suppression of its surrounding tissues,
      and was rated best on subtraction images. Conclusion: For radiosurgery of
      suprasellar tumors, inversion recovery sequences can be of valuable benefit for
      accurate delineation of optic pathway and radiosurgical dose planning in order to
      avoid radiation-induced normal tissue effects.

PMID- 29657893
TI  - Targeting accuracy at couch kick for a frameless image guided radiosurgery
      system.
AB  - Purpose/Objectives: Targeting accuracy at all possible couch angles needs to be
      carefully evaluated prior to initiating a frameless image-guided stereotactic
      radiosurgery program on a Linac for treating functional disorders such as
      trigeminal neuralgia. In this study, we report positioning accuracy with
      stereoscopic x-ray imaging over the complete range of couch rotation using
      anthropomorphic head phantoms. Materials/Methods: An anthropomorphic head phantom
      with three 5 mm tungsten BBs as hidden targets was CT simulated. A group of 7
      arcs was planned with couch angles from 0 to 90 degrees  in 15 degrees 
      increments. A pair of stereoscopic x-ray images that auto-matches to planning CT
      according to bony anatomy was utilized to position each BB to machine isocenter
      at all planned couch angles. Targeting accuracy was measured by stereoscopic x
      ray imaging of the BB itself, which provides the distance from the centroid of BB
      to the x-ray imaging isocenter. For each BB, the hidden target test was repeated
      5 times at couch 0 degrees  and 3 times at other couch angles, resulting in a
      total of 69 measurements, each with random initial setup deviation. Following the
      same workflow, a second anthropomorphic head phantom with two 5 mm BBs was
      utilized to evaluate localization accuracy at couch angles of 0 through 270
      degrees  in 15 degrees  increments, resulting in another 18 measurements.
      Results: Residual setup deviation following image guidance in the first head
      phantom was 0.6+/-0.1, 0.4+/-0.1, and 0.4+/-0.1 mm, respectively, at the three
      BBs, and 0.5+/-0.1 mm overall (N=69). Comparable results of 0.4+/-0.1 mm (N=18)
      were achieved with the second head phantom. Combining results from both phantoms,
      the targeting accuracy was 0.5+/-0.1 mm (range 0.2-0.8 mm). No apparent
      correlation was observed between targeting accuracy and couch rotation.
      Conclusions: Accurate positioning within 1 mm can be achieved with stereoscopic x
      ray imaging at any couch angle. Frameless image-guided stereotactic radiosurgery
      could achieve targeting accuracy similar to that of frame-based systems for high
      dose treatment of trigeminal neuralgia.

PMID- 29657894
TI  - Evaluation of multiple factors affecting normal brain dose in single-isocenter
      multiple target radiosurgery.
AB  - We investigated the effects of multiple planning factors on normal brain dose for
      single-isocenter VMAT stereotactic radiosurgery (SRS). Ten patients were
      retrospectively planned using a standardized objective function and all 16
      combinations of 2 versus 4 arcs, collimator angle 45 degrees  versus selected per
      beam to minimize area of normal brain exposed in the beams-eye-view, fixed jaw
      versus following the trailing MLC leaf, and a 2 Gy mean dose objective for
      healthy brain versus no low dose objective. Limiting the normal brain mean dose
      in the optimization objective function significantly reduced the low dose spill
      into the normal brain without changing target coverage. Jaw tracking and
      appropriate selection of collimator also reduced the low dose volume, but to a
      lesser extent. To reduce low dose spill into normal brain for single isocenter
      VMAT radiosurgery of multiple targets, it is important to incorporate a limit on
      low dose spill into the objective function. This study has implications beyond
      single-isocenter VMAT radiosurgery. When comparing different inverse-planned
      treatment techniques, metrics that are important for evaluation of plan quality
      must be included the objective function.

PMID- 29657895
TI  - Restricted single isocenter for multiple targets dynamic conformal arc (RSIMT
      DCA) technique for brain stereotactic radiosurgery (SRS) planning.
AB  - Purpose/Objectives: In stereotactic radiosurgery (SRS), the multiple isocenters
      for multiple targets dynamic conformal arc (MIMT DCA) technique is traditionally
      used to treat multiple brain metastases, with one isocenter for each target. The
      single isocenter for multiple targets (SIMT) technique has recently been adopted
      to reduce the treatment time at the cost of plan quality. The objective of this
      study was to develop a restricted single isocenter for multiple targets DCA
      (RSIMT DCA) technique that can significantly reduce the treatment time but still
      maintain similar plan quality as the MIMT DCA technique. Materials and Methods:
      Treating multiple brain metastases with a single isocenter poses a challenge to
      SRS planning using DCA beams that are intrinsically 3D and do not modulate the
      beam intensity to spare the normal tissue between targets. To address this
      obstacle, we have developed a RSIMT DCA technique and used it to treat SRS
      patients with multiple brain metastases since February 2015. This planning
      approach is similar to the SIMT technique except that the number of targets for
      each isocenter is restricted and the distance between the isocenter and target is
      limited. In this technique, the targets are first split into batches so that all
      targets in a batch are within a chosen distance (e.g., 7 cm) of each other. All
      targets in a batch are combined into one target and the geometric center of the
      combined target is the isocenter for the group of DCA beams associated with that
      batch. Each DCA group typically consists of 3-4 DCA beams to irradiate 1-3
      targets. For each DCA beam, the collimator angle is adjusted to minimize the
      exposure of normal tissue between targets. The dose of each treatment group is
      normalized so that the maximal point dose to the combined target is 125% of the
      prescription dose, which is equivalent to normalize the prescription dose to 80%
      isodose line. If the maximal point dose of a target is <123%, an additional beam
      is used to boost the maximal point dose of that target to 125%. To evaluate the
      plan quality, we randomly selected 10 cases planned with the RSIMT DCA technique,
      and re-planned them using the MIMT DCA technique. There were in total 38 PTVs,
      and 22 isocenters were used to treat all of these targets. The prescription for
      each target was 20 Gy with a maximal point dose of 25 Gy. Plan quality indexes
      were calculated and compared. Paired sample t-test was performed to determine if
      the mean normalized difference, (RSIMT-MIMT)/MIMT of each plan index was
      statistically significantly (p-value < 5%) larger than 0. Results: Satisfactory
      PTV coverage (V20Gy>95% and V19Gy=100%) was achieved for all plans using either
      technique. Most PTVs have a maximal point dose between 24.9 and 25.1 Gy, with 2
      PTVs between 24.5 and 24.9 Gy. Overall, the plan quality was slightly better for
      the MIMT DCA technique and the normalized difference was statistically
      significantly larger than 0 for all investigated dose quality indexes. The
      normalized difference of body mean dose and conformity index (CI) between the
      RSIMT and MIMT techniques was respectively 4.2% (p=0.002) and 9.4% (p=0.001),
      indicating similar plan quality globally and in the high dose area. The
      difference was more pronounced for the mid-to-low dose spillage with the ratios
      of V12Gy and V10Gy/VPTV being 13.9% (p=3.8*10-6) and 14.9% (p=1.3*10-5),
      respectively. The treatment time was reduced by 30%-50% with the RSIMT DCA
      technique. Conclusion: The RSIMT DCA technique can produce satisfactory SRS plans
      for treating multiple targets and can significantly reduce the treatment time.

PMID- 29657896
TI  - A comparison of the convolution and TMR10 treatment planning algorithms for Gamma
      Knife(r) radiosurgery.
AB  - Aims: To compare the accuracies of the convolution and TMR10 Gamma Knife
      treatment planning algorithms, and assess the impact upon clinical practice of
      implementing convolution-based treatment planning. Methods: Doses calculated by
      both algorithms were compared against ionisation chamber measurements in
      homogeneous and heterogeneous phantoms. Relative dose distributions calculated by
      both algorithms were compared against film-derived 2D isodose plots in a
      heterogeneous phantom, with distance-to-agreement (DTA) measured at the 80%, 50%
      and 20% isodose levels. A retrospective planning study compared 19 clinically
      acceptable metastasis convolution plans against TMR10 plans with matched shot
      times, allowing novel comparison of true dosimetric parameters rather than total
      beam-on-time. Gamma analysis and dose-difference analysis were performed on each
      pair of dose distributions. Results: Both algorithms matched point dose
      measurement within +/-1.1% in homogeneous conditions. Convolution provided
      superior point-dose accuracy in the heterogeneous phantom (-1.1% v 4.0%), with no
      discernible differences in relative dose distribution accuracy. In our study
      convolution-calculated plans yielded D99% 6.4% (95% CI:5.5%-7.3%,p<0.001) less
      than shot matched TMR10 plans. For gamma passing criteria 1%/1mm, 16% of targets
      had passing rates >95%. The range of dose differences in the targets was 0.2
      4.6Gy. Conclusions: Convolution provides superior accuracy versus TMR10 in
      heterogeneous conditions. Implementing convolution would result in increased
      target doses therefore its implementation may require a revaluation of
      prescription doses.

PMID- 29657898
TI  - Slow Elevation in Protein C Activity without a PROC Mutation in a Neonate with
      Intracranial Hemorrhage.
AB  - Severe protein C (PC) deficiency leads to purpura fulminans and stroke in
      newborns. However, the clinical impact of plasma PC activity on the development
      of neonatal cerebral disease remains elusive. We report a case of hemorrhagic
      stroke associated with neonatal asphyxia and severe PC deficiency. Plasma PC and
      protein S activity 7 days after birth was 12% and 43%, respectively. No PROC
      mutation was found. PC levels did not exceed 20% until 2 months of age, even in
      the absence of consumption coagulopathy or vitamin K deficiency. Neither
      thromboembolic nor hemorrhagic events occurred during the infusion of activated
      PC concentrate (twice weekly, up to 68 days after birth). The PC activity levels
      gradually increased to the standard value for age by 9 months of age. The present
      case showed that neonatal PC deficiency without a PROC mutation caused an
      intracranial hemorrhage before a slow increase in PC activity.

PMID- 29657899
TI  - Exercise Endocrinology: Guidance for Future Research Direction and Focus.

PMID- 29657900
TI  - Occipital and Cingulate Hypometabolism are Significantly Under-Reported on 18
      Fluorodeoxyglucose Positron Emission Tomography Scans of Patients with Lewy Body
      Dementia.
AB  - Objective: To determine whether occipital and cingulate hypometabolism is being
      under-reported or missed on 18-fluorodeoxyglucose positron emission tomography
      (FDG-PET) CT scans in patients with Dementia with Lewy Bodies (DLB). Background:
      Recent studies have reported higher sensitivity and specificity for occipital and
      cingulate hypometabolism on FDG-PET of DLB patients. Methods: This retrospective
      chart review looked at regions of interest (ROI's) in FDG-PET CT scan reports in
      35 consecutive patients with a clinical diagnosis of probable, possible, or
      definite DLB as defined by the latest DLB Consortium Report. ROI's consisting of
      glucose hypometabolism in frontal, parietal, temporal, occipital, and cingulate
      areas were tabulated and charted separately by the authors from the reports. A
      blinded Nuclear medicine physician read the images independently and marked ROI's
      separately. A Cohen's Kappa coefficient statistic was calculated to determine
      agreement between the reports and the blinded reads. Results: On the radiology
      reports, 25.71% and 17.14% of patients reported occipital and cingulate
      hypometabolism respectively. Independent reads demonstrated significant
      disagreement with the proportion of occipital and cingulate hypometabolism being
      reported on initial reads: 91.43% and 85.71% respectively. Cohen's Kappa
      statistic determinations demonstrated significant agreement only with parietal
      hypometabolism (p<0.05). Conclusion: Occipital and cingulate hypometabolism is
      under-reported and missed frequently on clinical interpretations of FDG-PET scans
      of patients with DLB, but the frequency of hypometabolism is even higher than
      previously reported. Further studies with more statistical power and receiver
      operating characteristic analyses are needed to delineate the sensitivity and
      specificity of these in vivo biomarkers.

PMID- 29657901
TI  - Triggerable Multivalent Glyconanoparticles for Probing Carbohydrate-Carbohydrate
      Interactions.
AB  - Carbohydrate-carbohydrate interactions are proposed to be biologically
      significant but have lower affinities than the well-studied carbohydrate-protein
      interactions. Here we introduce multivalent glyconanostructures where the surface
      expression of lactose can be triggered by an external stimulus, and a gold
      nanoparticle core enables colorimetric signal outputs to probe binding.
      Macromolecular engineering of a responsive polymer "gate" enables the lactose
      moieties to be presented only when an external stimulus is present, mimicking how
      nature uses enzymes to dynamically regulate glycan expression. Two different
      carbohydrate-carbohydrate interactions are investigated using this tool.

PMID- 29657902
TI  - Inhibitory Effects of Angiotensin II Receptor Blockade on Human Tenon Fibroblast
      Migration and Reactive Oxygen Species Production in Cell Culture.
AB  - Purpose: We investigate the effect of angiotensin receptor blockade on the
      migration of human Tenon fibroblasts (HTF), using irbesartan, an angiotensin II
      receptor type 1 (AT1R) blocker (ARB) as a potential antifibrotic agent in
      glaucoma filtration surgery. Methods: Confluent HTF cultures were scratched with
      a 1 mL pipette tip and treated with either irbesartan (10, 50, and 100 MUg/mL) or
      angiotensin II (2 MUg/mL). The extent of HTF migration up to 30 hours, and cell
      number and morphology at 72 hours was evaluated. To assess the effect on reactive
      oxygen species (ROS) level, HTF were treated with either irbesartan (10 MUg/mL)
      or angiotensin II (2 MUg/mL) for 24 hours after scratching, and then stained with
      dihydroethidium (DHE) before evaluation by confocal microscopy. Results:
      Irbesartan inhibited HTF migration by 50% to 70% compared to controls (P < 0.05).
      Levels of ROS were almost completely attenuated by irbesartan (DHE fluorescence
      intensity of 5.68E-09) (P < 0.05). Irbesartan reduced cell numbers by 50% and
      induced morphologic changes with loss of pseudopods (P < 0.05). Conversely,
      angiotensin II increased cell numbers up to 4-fold while retaining cell
      viability. Conclusions: Irbesartan inhibited HTF migration and ROS production. It
      also reduced cell numbers and altered HTF morphology. Angiotensin II increased
      cell number without altering morphology. This initial study warrants future
      investigations for further potential antifibrotic effects of this drug.
      Translational Relevance: This in vitro study focused on investigations of
      irbesartan's effects on HTF migration, ROS production, as well as HTF cell
      numbers and morphology. It suggests a potential therapeutic strategy worth
      further exploration with a view towards postoperative wound healing modulation in
      glaucoma filtration surgery.

PMID- 29657903
TI  - Obstructive Sleep Apnea as a Risk Factor for Atrial Fibrillation: A Meta
      Analysis.
AB  - Objectives: To conducted a meta-analysis assessing the relationship between
      Obstructive Sleep Apnea (OSA) and the risk of Atrial Fibrillation (AF). Methods:
      We searched PUBMED, Medline, and Cochrane Library using the keywords "atrial
      fibrillation", "obstructive sleep apnea" and "sleep disordered breathing (SDB)".
      All subjects included had established diagnosis of OSA/SDB. We then compared the
      occurrence of AF versus no AF. Analysis done with Comprehensive Meta-Analysis
      package V3 (Biostat, USA). Results: A total of 579 results were generated.
      Duplicates were removed and 372 records were excluded based on irrelevant
      abstracts, titles, study design not consistent with the stated outcome, or full
      text unavailable. Twelve studies meeting the inclusion criteria were reviewed in
      full-text; 2 of these articles were eventually removed due to unconfirmed OSA
      diagnostic modality, and one was also removed based on a control group
      inconsistent with the other studies. Therefore, a total of 9 studies were
      included (n=19,837). Sample sizes ranged from n=160 patients to n=6841 patients.
      The risk of AF was found to be higher among OSA/SDB versus control group (OR;
      2.120, C.I: 1.845-2.436, Z; 10.598 p: <0.001). The heterogeneity observed for the
      pooled analysis was Q-value; 22.487 df (Q); 8 P-value; 0.004, I-squared; 64.424
      Tau2; 0.098, suggesting appropriate study selection and moderate heterogeneity.
      Conclusion: OSA/SDB is strongly associated with AFib confirming the notion that
      OSA/SDB populations are high risk for development of AF. Prospective studies are
      needed to ascertain the effect of the treatment of OSA/SDB for the prevention of
      AF, a growing health burden with serious consequences.

PMID- 29657905
TI  - Knowledge of Postgraduate Medical Trainees Regarding Epidemiology.
AB  - Introduction An understanding of epidemiology is fundamental for designing
      research and understanding evidence-based medicine (EBM). The purpose of our
      study was to determine the knowledge of epidemiology among postgraduate medical
      trainees. Methods We carried out a cross-sectional study from January 2017 to
      June 2017 at the Regional Centre Islamabad, College of Physicians and Surgeons
      Pakistan. About 204 postgraduate medical trainee were enrolled in the study after
      taking written consent. All of the participants were working as a postgraduate
      medical trainee in different hospitals of Rawalpindi and Islamabad. A self
      designed structured questionnaire containing 20 multiple choice questions
      regarding knowledge of epidemiology was given to all the participants. Knowledge
      of epidemiology was measured and compared with gender, hospital, and previous
      history of research. Statistical Package for the Social Sciences (SPSS), version
      21.0 (IBM, Armonk, NY) was used for data analysis. Results Out of 204
      participants, 46.1% participants were males while 53.9% were females. The mean
      age of the participant was 28.5 +/- 2.5. Majority fo the trainees (33.8%) were
      training in an Internal Medicine residency program. Most of the trainees (76%)
      had average knowledge of epidemiology while 18.6% of the trainees had good
      knowledge. Only 17.6% had some experience of research projects in the past, but
      this was not related to knowledge of epidemiology (p > 0.05). Conclusion Only
      18.6% of the postgraduate trainees had good knowledge regarding epidemiology and
      76% had average knowledge. This knowledge did not relate to their gender,
      hospital settings, and previous experience of conducting research proposals and
      articles.

PMID- 29657904
TI  - Immunotherapy for Breast Cancer: Current and Future Strategies.
AB  - Purpose of Review: The breast tumor microenvironment is immunosuppressive and is
      increasingly recognized to play a significant role in tumorigenesis. A deeper
      understanding of normal and aberrant interactions between malignant and immune
      cells has allowed researchers to harness the immune system with novel
      immunotherapy strategies, many of which have shown promise in breast cancer. This
      review discusses the application of immunotherapy to the treatment of breast
      cancer. Recent Findings: Both basic science and clinical trial data are rapidly
      developing in the use of immunotherapy for breast cancer. The current clinical
      trial landscape includes therapeutic vaccines, immune checkpoint blockade,
      antibodies, cytokines, and adoptive cell therapy. Summary: Despite early
      failures, the application of immunotherapeutic strategies to the treatment of
      breast cancer holds promise.

PMID- 29657906
TI  - Imaging Characteristics of Dural Arteriovenous Fistulas Involving the Vein of
      Galen: A Comprehensive Review.
AB  - Vein of Galen aneurysmal malformation (VGAM) is a rare angiopathy, which most
      commonly presents in infancy. Although very rare, it is associated with high
      morbidity and mortality rates. In order to minimize such morbid rates, a prompt
      diagnosis followed by a timely initiation of management is crucial. Multiple
      antenatal and postnatal imaging techniques for the diagnosis have been described
      and discussed in the literature. However, to our knowledge, a comprehensive
      review exploring such a list of imaging options for VGAM has never been
      established. We aim to review the diagnostic tools to aid in better understanding
      of the investigative modalities physicians may choose from when treating patients
      with a VGAM.

PMID- 29657907
TI  - Comparing Surgical Site Infection and Scar Cosmesis Between Conventional Linear
      Skin Closure Versus Purse-string Skin Closure in Stoma Reversal - A Randomized
      Controlled Trial.
AB  - Introduction Stoma closure is one of the most frequently performed surgeries. The
      common complications are surgical site infection (SSI) and poor scar cosmesis.
      Purse-string sutures are expected to have less incidence of SSI due to the free
      drainage of secretions from the wound and possibly the early detection of a wound
      infection. Compared to the conventional linear closure, the purse-string closure
      technique is expected to have less wound infection, improved scar cosmesis, and
      good patient satisfaction because of a smaller size scar. Hence, a well
      structured study is required to substantiate the advantage of this technique.
      Methodology This randomized control trial was carried out for two years in a
      tertiary care centre in Southern India. Patients with various stoma reversals,
      including colostomy, as well as ileostomy reversal, were included in the study.
      Patients were divided into Group I - conventional linear skin suturing (n = 40)
      and Group II - purse-string closure (n = 40). After the closure of rectus muscle,
      the skin is closed using the purse-string method (subcuticular) in the
      experimental group. Results Both the groups were comparable with respect to age,
      gender, body mass index (BMI), the presence of co-morbidities, and indication for
      surgery. Stomal procedures were done (26.3%) for malignant cases. The difference
      in mean hospital days for both groups were statistically insignificant (11.95 vs.
      9.9; p = 0.927). The incidence of SSI between the groups were statistically
      significant (17 vs. 3; p = 0.003). The mean Patient and Observer Scar Assessment
      Scoring (POSAS) scores between the groups (65.30 vs. 83.40; p = 0.012) were
      statistically significant. This proved significant improvement in scar cosmesis
      in purse-string skin closure. At one month postoperative, the purse-string group
      had better patient satisfaction (3.08 vs. 4.48; p = 0.001), which was evidenced
      by a mean Likert 3 scale score. The mean visual analogue scale (VAS) score did
      not show any significant difference in pain between the groups. Conclusion Purse
      string skin closure for stoma reversal had significantly less incidence of SSI.
      The duration of antibiotic therapy was also less in purse-string skin closure
      patients as compared to linear skin closure patients. Purse-string skin closures
      significantly improved the scar outcome and patient satisfaction.

PMID- 29657908
TI  - A Rare Case of Coronary Artery Embolism in a Patient with d-Transposition of the
      Great Arteries with Prior Mustard Repair.
AB  - The dextro-transposition of great arteries (d-TGA) is a rare, congenital,
      cyanotic heart disease and there is a paucity of data regarding long-term
      cardiovascular outcomes. We present a rare case of non-ST-elevation myocardial
      infarction (NSTEMI) in a patient with surgically repaired d-TGA. A 43-year-old
      male who had previously undergone a Mustard atrial switch palliative procedure
      presented with chest pain and diaphoresis and was diagnosed with NSTEMI. A
      coronary angiogram revealed a small, underdeveloped, left anterior descending and
      a large, left circumflex coronary artery with an acute embolic lesion. The
      embolic lesion was secondary to atrial fibrillation and was successfully treated
      with aspiration thrombectomy. This case highlights the variations in coronary
      anatomy in surgically repaired d-TGA and the importance of recognizing the
      potential for long-term complications in these cases.

PMID- 29657909
TI  - Exposure of Dural Venous Sinuses: A Review of Techniques and Description of a
      Single-piece Troughed Craniotomy.
AB  - Intracranial lesions along the falx and tentorium often require exposure of a
      dural venous sinus. Craniotomies that cross a sinus should maximize exposure
      while minimizing the risk of sinus injury and provide a cosmetically appealing
      result with simple reconstruction techniques.  We describe the published
      techniques for exposing dural venous sinuses, and introduce a new technique for a
      single-piece craniotomy exposing the superior sagittal sinus or transverse sinus
      using drilled troughs. A review of the literature was performed to identify
      articles detailing operative techniques for craniotomies over dural venous
      sinuses. Our troughed craniotomy for dural sinus exposure is described in detail
      as well as our experience using this technique in 82 consecutive cases from 2007
      2015. Five distinct techniques for exposure of the dural venous sinus were
      identified in the literature. In our series of patients undergoing a trough
      craniotomy, there were no sinus injuries despite a range of various locations and
      pathology along the sagittal and transverse sinuses. Our technique was found to
      be safe and simple to reconstruct compared to other techniques found in the
      literature. A variety of different techniques for exposing the dural venous
      sinuses are available. A single-piece craniotomy using a trough technique is a
      safe means to achieve venous sinus exposure with minimal reconstruction required.
      Surgeons should consider this method when removing lesions adjacent to the falx
      or tentorium.

PMID- 29657910
TI  - Anterolateral Triangle: A Cadaveric Study with Neurosurgical Significance.
AB  - The anterolateral triangle is one of 10 surgical triangles of the cavernous sinus
      and serves as an important anatomic landmark for the skull base surgeon. There
      are few studies in the English literature that have precisely defined and
      measured the borders of the anterolateral triangle and little agreement has been
      made regarding the nomenclature within the English literature. A total of 12
      midsagittally hemisected adult human cadaveric head halves were dissected to
      expose the anterolateral triangle. The triangle was defined and measurements of
      the anterior, posterior, and lateral borders were taken. The mean lengths and
      standard deviations of the anterior, posterior, and lateral borders were 8.3 +/-
      2.2 mm, 5.9 +/- 2.0 mm, and 11.5 +/- 2.9 mm, respectively. The mean area and
      standard deviation were 20.46 +/- 9.30 mm2. The anterolateral triangle is helpful
      in understanding and planning surgical approaches to the cavernous sinus and
      middle cranial fossa. As such, normal anatomic relationships and the sizes of the
      anterolateral triangle must first be recognized to better access the pathologic
      changes within and around this region.

PMID- 29657911
TI  - Origins of tropospheric ozone interannual variation (IAV) over Reunion: A model
      investigation.
AB  - Observations from long-term ozonesonde measurements show robust variations and
      trends in the evolution of ozone in the middle and upper troposphere over Reunion
      Island (21.1 degrees S, 55.5 degrees E) in June-August. Here we examine possible
      causes of the observed ozone variation at Reunion Island using hindcast
      simulations by the stratosphere-troposphere Global Modeling Initiative chemical
      transport model (GMI-CTM) for 1992-2014, driven by assimilated Modern-Era
      Retrospective Analysis for Research and Applications (MERRA) meteorological
      fields. Reunion Island is at the edge of the subtropical jet, a region of strong
      stratospheric-tropospheric exchange (STE). Our analysis implies that the large
      interannual variation (IAV) of upper tropospheric ozone over Reunion is driven by
      the large IAV of the stratospheric influence. The IAV of the large-scale, quasi
      horizontal wind patterns also contributes to the IAV of ozone in the upper
      troposphere. Comparison to a simulation with constant emissions indicates that
      increasing emissions do not lead to the maximum trend in the middle and upper
      troposphere over Reunion during austral winter implied by the sonde data. The
      effects of increasing emission over southern Africa are limited to the lower
      troposphere near the surface in August - September.

PMID- 29657912
TI  - Manufacturing Nanoparticles with Orthogonally Adjustable Dispersibility in
      Hydrocarbons, Fluorocarbons, and Water.
AB  - Invited for this month's cover picture is the group of Prof. Dr. Andreas Hirsch
      from Friedrich Alexander University (Germany). The cover picture shows shell-by
      shell coated nanoparticle 'chameleons'-wet-chemically surface-modified
      nanoparticles that can reversibly adjust their dispersibility to entirely
      orthogonal solvent environments. Read the full text of their Full Paper at
      https://doi.org/10.1002/open.201800011.

PMID- 29657913
TI  - Triple Helicene Cage: Three-Dimensional pi-Conjugated Chiral Cage with Six
      [5]Helicene Units.
AB  - A three-dimensional pi-conjugated chiral cage with six [5]helicene units (a
      triple helicene cage) was synthesized for the first time. Taking advantage of the
      Yamamoto coupling reaction, the triflate-substituted triple [5]helicene, a
      strained and preorganized precursor, was dimerized to afford the target compound.
      Single-crystal X-ray diffraction analysis revealed the unique structural features
      of the triple helicene cage: a cage-shaped rigid structure with outer helical
      grooves and an inner chiral cavity. All-P and all-M enantiomers were separated
      successfully by HPLC over a chiral column and their chiroptical properties were
      characterized by circular dichroism spectra.

PMID- 29657914
TI  - Manufacturing Nanoparticles with Orthogonally Adjustable Dispersibility in
      Hydrocarbons, Fluorocarbons, and Water.
AB  - We describe a universal wet-chemical shell-by-shell coating procedure resulting
      in colloidal titanium dioxide (TiO2) and iron oxide (Fe3O4) nanoparticles with
      dynamically and reversibly tunable surface energies. A strong covalent surface
      functionalization is accomplished by using long-chained alkyl-, triethylenglycol
      , and perfluoroalkylphosphonic acids, yielding highly stabilized core-shell
      nanoparticles with hydrophobic, hydrophilic, or superhydrophobic/fluorophilic
      surface characteristics. This covalent functionalization sequence is extended
      towards a second noncovalent attachment of tailor-made nonionic amphiphilic
      molecules to the pristine coated core-shell nanoparticles via solvophobic (i.e.
      either hydrophobic, lipophobic, or fluorophobic) interactions. Thereby,
      orthogonal tuning of the surface energies of nanoparticles via noncovalent
      interactions is accomplished. As a result, this versatile bilayer coating process
      enables reversible control over the colloidal stability of the metal oxide
      nanoparticles in fluorocarbons, hydrocarbons, and water.

PMID- 29657915
TI  - Macromolecular Crowding May Significantly Affect the Performance of an MRI
      Contrast Agent: A 1H NMR Spectroscopy, Microimaging, and Fast-Field-Cycling NMR
      Relaxometry Study.
AB  - Contrast enhancement agents are often employed in magnetic resonance imaging
      (MRI) for clinical diagnosis and biomedical research. However, the current theory
      on MRI contrast generation does not consider the ubiquitous presence of
      macromolecular crowders in biological systems, which poses the risk of inaccurate
      data interpretation and misdiagnosis. To address this issue, herein the
      macromolecular crowding effects on MRI contrast agent are investigated with the
      1H relaxation rate of water in aqueous solutions of Dotarem with different
      concentrations of macromolecules. Two representative macromolecular crowder
      systems are used: polyethylene glycol (with no specific secondary structure) and
      bovine serum albumin (with compact secondary and tertiary structures). The water
      1H relaxation rates in various solutions are measured in a fixed magnetic field
      and in variable magnetic fields. The results show significant crowding effects
      for both crowders. The relaxation rate is proportional to the concentration of
      the MRI contrast agent but shows conspicuous superlinearity with respect to the
      concentration of the crowder. The size of polyethylene glycol does not affect the
      relaxivity of water in Dotarem solutions. The above effects are verified with T1-
      and T2-weighted NMR microimages. These results highlight the importance of the
      effect of macromolecular crowding on the MRI contrast agent and are valuable for
      understanding the mechanism of MRI contrast agents and designing new-generation
      MRI contrast agents.

PMID- 29657917
TI  - Hemophagocytic lymphohistiocytosis (HLH) secondary to disseminated histoplasmosis
      in the setting of Acquired Immunodeficiency Syndrome (AIDS).
AB  - Hemophagocytic lymphohistiocytosis (HLH) is a rare and aggressive disease
      involving immune system over-activation leading to hemophagocytosis. HLH requires
      early diagnosis and prompt treatment initiation, especially in patients with
      Acquired Immunodeficiency Syndrome (AIDS). We present a case of a middle-aged
      male with AIDS and renal failure, who developed HLH secondary to disseminated
      histoplasmosis. Etoposide chemotherapy as recommended by the HLH 2004 Guidelines
      was deferred and treatment focused instead on anti-fungal therapy. Anti
      retroviral therapy followed thereafter.

PMID- 29657916
TI  - Using New Approaches in Neurobiology to Rethink Stress-Induced Amnesia.
AB  - Purpose of Review: Psychological stress can impact memory systems in several
      different ways. In individuals with healthy defense and coping systems, stress
      results in the formation of negatively valenced memories whose ability to induce
      emotional and somatic distress subsides with time. Vulnerable individuals,
      however, go on to develop stress-related disorders such as post-traumatic stress
      disorder (PTSD) and suffer from significant memory abnormalities. Whether
      expressed as intrusive trauma memories, partial amnesia, or dissociative amnesia,
      such abnormalities are thought to be the core source of patients' symptoms, which
      are often debilitating and implicate an entire socio-cognitive-affective
      spectrum. Recent Findings: With this in mind, and focusing on stress-responsive
      hippocampal microcircuits, this article highlights recent advances in the
      neurobiology of memory that allow us to (1) isolate and visualize memory
      circuits, (2) change their activity using genetic tools and state-dependent
      manipulations, and (3) directly examine their impact on socio-affective circuits
      and global network connectivity. By integrating these approaches, we are now in a
      position to address important questions that have troubled psychiatry for a long
      time-questions such as are traumatic memories special, and why are stress effects
      on memory diverse. Summary: Furthering our fundamental understanding of memory in
      the framework of adaptive and maladaptive stress responses has the potential to
      boost the development of new treatments that can benefit patients suffering from
      psychological trauma.

PMID- 29657918
TI  - Effect of arsenic acid withdrawal on hepatotoxicity and disruption of erythrocyte
      antioxidant defense system.
AB  - We investigated the effects of withdrawal from Sodium arsenite (NaAsO2) on the
      hepatic and antioxidant defense system in male Wistar rats using a before and
      after toxicant design. Rats were orally gavaged daily with varying doses of
      NaAsO2 for a period of 4 weeks. One half of the population was sacrificed and the
      remaining half had the toxicant withdrawn for another further 4 weeks.
      Biochemical and immunohistochemical techniques were used to assess the impact of
      withdrawal on the erythrocyte and hepatic systems. Exposure of Wistar rats to
      NaASO2 led to a significant (p < 0.05) increase in hepatic and erythrocyte
      markers of oxidative stress (malondialdehyde, thiol contents and hydrogen
      peroxide generation). Concurrently, there was a significant (p < 0.05) increase
      in hepatic and erythrocyte antioxidant enzymes (glutathione-S-transferase,
      glutathione peroxidase and superoxide dismutase) following exposure. Withdrawal
      from NaAsO2 exposure led to a decline in both erythrocyte and hepatic markers of
      oxidative stress and together with a significant improvement in antioxidant
      defense system. Histopathology and immunohistochemistry revealed varying degrees
      of recovery in hepatocyte ultrastructure alongside increased expression of the
      pro-survival protein Kinase B (Akt/PKB) after 4 weeks of NaAsO2 withdrawal.
      Conclusively, withdrawal from exposure led to a partial recovery from oxidative
      stress-mediated hepatotoxicity and derangements in erythrocyte antioxidant system
      through Akt/PKB pathway.

PMID- 29657919
TI  - Exposure to radio-frequency electromagnetic waves alters acetylcholinesterase
      gene expression, exploratory and motor coordination-linked behaviour in male
      rats.
AB  - Humans in modern society are exposed to an ever-increasing number of
      electromagnetic fields (EMFs) and some studies have demonstrated that these waves
      can alter brain function but the mechanism still remains unclear. Hence, this
      study sought to investigate the effect of 2.5 Ghz band radio-frequency
      electromagnetic waves (RF-EMF) exposure on cerebral cortex acetylcholinesterase
      (AChE) activity and their mRNA expression level as well as locomotor function and
      anxiety-linked behaviour in male rats. Animals were divided into four groups
      namely; group 1 was control (without exposure), group 2-4 were exposed to 2.5 Ghz
      radiofrequency waves from an installed WI-FI device for a period of 4, 6 and 8
      weeks respectively. The results revealed that WiFi exposure caused a significant
      increase in anxiety level and affect locomotor function. Furthermore, there was a
      significant decrease in AChE activity with a concomitant increase in AChE mRNA
      expression level in WiFi exposed rats when compared with control. In conclusions,
      these data showed that long term exposure to WiFi may lead to adverse effects
      such as neurodegenerative diseases as observed by a significant alteration on
      AChE gene expression and some neurobehavioral parameters associated with brain
      damage.

PMID- 29657920
TI  - Sub-acute administration of lower doses of nicotine caused sex-dependent
      improvement of renal function in Wistar rats.
AB  - The adverse and beneficial health effects of nicotine (NIC), the major alkaloid
      found in cigarettes and tobacco, are controversial. Most studies on NIC have
      focused on its effects on cardiovascular and nervous functions. This study aimed
      at determining dose- and sex-specific effects of sub-acute (28 days) NIC
      administration on some indices of kidney function in Wistar rats. Forty rats (20
      males and 20 females), 8-9 weeks old (each housed in separate metabolic cage),
      were used for this study such that graded doses of NIC (1, 2 and 4 mg/kg i.p. for
      28 days) were administered to both sexes while each control received distilled
      water at 0.2 mL/100 g i.p. Blood was collected under ketamine anesthesia (10
      mg/kg i.m) for analyses and results obtained were compared at p < 0.05. The
      result showed beneficial alterations in plasma and urine level of creatinine,
      urea and uric acid (p < 0.05) as well as plasma and urine electrolyte level (Na+
      and K+) in both sexes (p < 0.05). Also, there was significant improvement in
      creatinine clearance (p < 0.05) with no appreciable difference in their
      histological examination. Although these beneficial effects were more pronounced
      in the female than in the male (p < 0.05), administration at the highest dose
      showed potentially deleterious alterations from normal beneficial trend (p <
      0.05) in both sexes. It was concluded that sub-acute administration of lower
      doses of NIC improves kidney function of Wistar rats; an effect that was more
      pronounced in the females than their male counterparts.

PMID- 29657921
TI  - Toxic effects of polybrominated diphenyl ethers (BDE 47 and 99) and localization
      of BDE-99-induced cyp1a mRNA in zebrafish larvae.
AB  - Polybrominated diphenyl ethers (PBDEs) were once widely used as flame retardants
      in furniture and electronic products, and contamination persists in developing
      countries due to the dismantling of electronic waste. Our previous study
      confirmed that 2,2',4,4',5-pentabromodiphenyl ether (BDE-99) induced cytochrome
      P450 1A (Cyp1a) via aryl hydrocarbon receptor (Ahr)-mediated signaling in the
      zebrafish liver cell line (ZFL) in vitro. In this study, the toxicities of BDE-47
      and BDE-99 at environmentally relevant concentrations (50 and 500 nM) were
      evaluated in newly hatched zebrafish (Danio rerio) larvae in vivo. A time-course
      study (8, 24, 48, and 96 h) was performed. BDE-99 was observed to cause yolk sac
      edema and pericardial edema after 72 h of exposure. Real-time polymerase chain
      reaction assay and whole-mount in situ hybridization assay confirmed cyp1a
      induction by BDE-99 in the liver and intestine. Continuous down-regulation of
      trbeta by as much as 2.1-fold after 96 h and transient down-regulation of ttr by
      7.1-fold after 24 h indicated the interference of BDE-99 in the thyroid hormone
      system. cyp1a induction was also observed in BDE-47-treated larvae, but cellular
      localization of cyp1a was not confirmed by whole-mount in situ hybridization. The
      induction of four cyp1 genes (cyp1a, cyp1b1, cyp1c1 and cyp1c2) by both BDE
      congeners warrants further study to understand the in vivo metabolism of BDE-47
      and BDE-99 and the dioxin-like toxicity potencies of the OH-/MeO-PBDEs. The data
      obtained in this study will aid the characterization of molecular disorders
      caused by PBDEs in fish and help to delineate better models for toxicity
      assessment of environmental pollutants in ecological systems and in other
      vertebrates such as humans.

PMID- 29657922
TI  - Gastro-protective effect of methanol extract of Vernonia amygdalina (del.) leaf
      on aspirin-induced gastric ulcer in Wistar rats.
AB  - This study investigated the protective effects of methanol extract of Vernonia
      amygdalina leaf (MEVA) on aspirin induced gastric ulcer in rats. Thirty Wistar
      rats, 150-200 g were divided into six groups as follows: Group 1 (control) rats
      received 2 mL/kg of propylene glycol for 28 consecutive days. Group 2 (Ulcer
      Control) received 150 mg/kg/day of aspirin suspended in 3 mL of 1%
      carboxymethylcellulose in water orally for 3 consecutive days during which the
      rats were fasted for the induction of ulcer. Group 3 received cimetidine at 100
      mg/kg/day orally for 28 consecutive days and thereafter treated as group 2.
      Groups 4, 5 and 6 received MEVA orally at 200, 300 and 400 mg/kg/day respectively
      for 28 consecutive days and thereafter were treated with aspirin as group 2. All
      the animals were sacrifice at the end of the study to determine the gastric pH,
      gastric acidity, gastric ulcer score, haematological indices, superoxide
      dismutase (SOD) activity, reduced glutathione (GSH) and Lipid peroxidation (LPO)
      levels. The result showed that aspirin significantly (p < 0.05) increased gastric
      ulcer score and index, decreased gastric pH, gastric acidity, SOD activity, GSH
      level as well as increased LPO level. It induced significant necrosis of the
      stomach tissue. Administration of MEVA significantly (p < 0.05) increased gastric
      pH, but decreased gastric acid secretion and reversed alteration of
      haematological parameters. It also significantly (p < 0.05) increased SOD
      activity, GSH level and decreased LPO level. The results suggest that Vernonia
      amygdalina possesses gastro-protective properties against aspirin-induced gastric
      ulcer.

PMID- 29657923
TI  - A HYBRID APPROACH TO SIMULATE TISSUE BEHAVIOR DURING SURGICAL SIMULATION.
AB  - Modeling interaction between deformable and rigid objects efficiently and
      accurately is one of the most important tasks for interactive surgical
      simulation. The Finite Element Method (FEM) has become very popular in this
      context due to its versatility in representing elastic bodies with irregular
      geometric features and diverse material properties. In this work we propose a
      hybrid FEM approach to simulating realistic tissue behavior that uses a non
      linear formulation in the vicinity of the interaction while employing a less
      accurate and inexpensive linear formulation elsewhere. A semi-implicit time
      stepping is used for the non-linear portion of the domain. This avoids expensive
      domain decomposition strategies required to maintain consistency at the interface
      and allows for regular system assembly using a non-overlapping interface and
      single solver for both domains. This study demonstrates the advantages of our
      novel approach, especially for the case of real-time surgical simulation.

PMID- 29657925
TI  - Biofilm Formation in Nonmultidrug-resistant Escherichia coli Isolated from
      Patients with Urinary Tract Infection in Isfahan, Iran.
AB  - Background: Escherichia coli is a Gram-negative, opportunistic human pathogen in
      which increasing antibiotic resistance is a great concern for continued human
      survival. Although biofilm formation is a mechanism that helps E. coli to survive
      in unfavorable conditions, according to the importance of biofilm formation in
      developing the antibiotic resistance here, we studied the relation between
      antibiotic resistance and in vitro qualitative rating method biofilm formation in
      E. coli isolated from patients with urinary tract infection (UTI). Materials and
      Methods: The clinical isolates of E. coli (n = 100) were collected from urine of
      patients with UTI attending Isfahan Alzahra hospital. The strains were confirmed
      as E. coli using biochemical tests and molecular method. The Kirby-Bauer disk
      diffusion tests were done according to the Clinical and Laboratory Standards
      Institute protocol, and the biofilm synthesis was performed by microplate method.
      The binary logistic test was applied and P < 0.05 was considered statistically
      significant. Results: Our results showed a high outbreak of multidrug-resistant
      (MDR) E. coli strains (73%) and the highest resistance was observed toward
      ampicillin. The prevalence of biofilm producer isolates was 80% that 29% produced
      strong biofilm. The distribution of non-MDR isolates was high among strong
      biofilm producers, which shows a significant negative correlation between biofilm
      production and MDR pattern (P < 0.001). Conclusions: We found a negative
      correlation between MDR phenotype and biofilm formation capacity. This transmits
      the concept that more antibiotic susceptibility of strong biofilm producers may
      be due to the reduced exposure to multiple antibiotics.

PMID- 29657924
TI  - Palliative care for adolescents and young adults with cancer.
AB  - Adolescents and young adults (AYAs) with cancer represent a unique and
      challenging group of patients with distinct developmental and psychosocial needs
      that may be unrecognized or unmet during their cancer experience. Palliative care
      refers to the total care of a patient, regardless of his or her disease status,
      and aims to improve quality of life by controlling symptoms and alleviating
      physical, social, psychological, and spiritual suffering. Integrating palliative
      care into standard oncology practice for AYAs is therefore valuable, if not
      imperative, in improving their overall cancer experience. In this review, we
      aimed to describe the scope, benefits, and challenges of palliative care for AYA
      oncology patients. We provide a broad impression of the existing literature
      describing or investigating palliative care in this population. Put together, the
      evidence suggests that palliative care is not only needed, but can also be
      critically beneficial to patients, families, and health care professionals alike.
      As we increase public and professional awareness of the needs and applications of
      palliative care for AYA patients with cancer, we will ultimately enable better
      psychosocial outcomes of the AYA patients and their larger communities.

PMID- 29657926
TI  - Efficacy of Group Cognitive-behavioral Therapy in Maintenance Treatment and
      Relapse Prevention for Bipolar Adolescents.
AB  - Background: Despite conducting wide-ranging of pharmacotherapy for bipolar
      adolescents, many of them are showing a deficit in functioning with high relapse
      rate. The aim of the current study was to develop a manual and investigate the
      efficacy of group cognitive-behavioral therapy (G-CBT) for female bipolar
      adolescents. Materials and Methods: During the first qualitative phase of a mixed
      methods study, a manual of G-CBT was developed. Then, 32 female bipolar
      adolescents aged 12-19 years old, receiving usual maintenance medications (UMM),
      were selected. Participants were randomized to the control (UMM) and intervention
      group (5, 2 h weekly sessions based on G-CBT manual with UMM). The parents in
      intervention group participated in three parallel sessions. All participants
      filled the following questionnaires before 1, 3, and 6 months after the
      initiation of the study: Young Mania Rating Scale, Children Depression Inventory
      and Global Assessment of Functioning. The results were analyzed using SPSS 21
      software. The concurrent qualitative phase was analyzed through thematic
      analysis. Results: The results showed no significant differences in all
      questionnaires' scores through intervention and follow-up sessions (P > 0.05).
      However, using cutoff point of CDI, G-CBT was effective for intervention group
      (relapse rate: 25% vs. 44.4%). Two themes were extracted from the second
      qualitative phase: emotion recognition and emotion regulation, especially in
      anger control. Conclusions: The results showed that the addition of G-CBT to UMM
      leads to decrease in the depressive scores but has no effect on manic symptoms
      and relapse rate.

PMID- 29657928
TI  - Cytotoxicity of Sargassum angustifolium Partitions against Breast and Cervical
      Cancer Cell Lines.
AB  - Background: Marine organisms produce a variety of compounds with pharmacological
      activities including anticancer effects. This study attempt to find cytotoxicity
      of hexane (HEX), dichloromethane (DCM), and butanol (BUTOH) partitions of
      Sargassum angustifolium. Materials and Methods: S. angustifolium was collected
      from Bushehr, a Southwest coastline of Persian Gulf. The plant was extracted by
      maceration with methanol-ethyl acetate. The extract was evaporated under vacuum
      and partitioned by Kupchan method to yield HEX, DCM, and BUTOH partitions. The
      cytotoxic activity of the extract (150, 450, and 900 MUg/ml) was investigated
      against MCF-7 (breast cancer), HeLa (cervical cancer), and human umbilical vein
      endothelial cells cell lines by mitochondrial tetrazolium test assay after 72 h.
      Results: The cell survivals of HeLa and MCF-7 cell were decreased by increasing
      the concentration of extracts from 150 MUg/ml to 900 MUg/ml. The median growth
      inhibitory concentration value of HEX partition was 71 and 77 MUg/ml against HeLa
      and MCF-7, dichloromethane partition was 36 and 88 MUg/ml against HeLa and MCF-7,
      respectively. BUTOH partition was 25 MUg/ml against MCF-7. Conclusion: This study
      reveals that different partitions of S. angustifolium have cytotoxic activity
      against cancer cell lines.

PMID- 29657927
TI  - Gene Expression Analysis of Two Epithelial-mesenchymal Transition-related Genes:
      Long Noncoding RNA-ATB and SETD8 in Gastric Cancer Tissues.
AB  - Background: Cancer is the second cause of death after cardiovascular diseases
      worldwide. Tumor metastasis is the main cause of death in patients with cancer;
      therefore, unraveling the molecular mechanisms involved in metastasis is
      critical. Epithelial-mesenchymal transition (EMT) is believed to promote tumor
      metastasis. Based on the critical roles of long noncoding RNA-ATB (lncRNA-ATB)
      and SETD8 genes in cancer pathogenesis and EMT, in this study, we aimed to assess
      expression profile and clinicopathological relevance of these two genes in human
      gastric cancer. Materials and Methods: Quantitative real-time polymerase chain
      reaction was performed to assess these gene expressions in gastric cancer tissues
      and various cell lines. The associations between these gene expressions and
      clinicopathological characteristics were also analyzed. Results: Insignificant
      downregulation of lncRNA-ATB and significant upregulation of SETD8 in cancerous
      versus noncancerous gastric tissues were observed. Among different examined cell
      lines, all displayed both genes expression. Except for a significant inverse
      correlation between the expression levels of lncRNA-ATB and depth of invasion (T)
      and a direct association between SETD8 levels and advanced tumor grades, no
      significant association was found with other clinicopathological characteristics.
      Conclusion: lncRNA-ATB and SETD8 genes may play a critical role in gastric cancer
      progression and may serve as potential diagnostic/prognostic biomarkers in cancer
      patients.

PMID- 29657929
TI  - Poly(hydroxybutyrate)/chitosan Aligned Electrospun Scaffold as a Novel Substrate
      for Nerve Tissue Engineering.
AB  - Background: Reconstruction of nervous system is a great challenge in the
      therapeutic medical field. Nerve tissue engineering is a novel method to
      regenerate nervous system in human health care. Tissue engineering has introduced
      novel approaches to promote and guide peripheral nerve regeneration using
      submicron and nanoscale fibrous scaffolds. Materials and Methods: In this study,
      9 wt% poly(3-hydroxybutyrate) (PHB) solutions with two different ratios of
      chitosan (CTS) (15%, and 20%) were mixed in trifluoroacetic acid as a cosolvent.
      Thereafter, random and aligned PHB/CTS scaffolds were fabricated by
      electrospinning method in an appropriate condition. Results: Average diameters
      for aligned PHB, PHB/CTS 85:15 and PHB/CTS 80:20 were obtained as 675 nm, 740.3
      nm, and 870.74 nm, which was lesser than random fibers. The solution components
      entity authenticity was approved by Fourier transform infrared. The addition of
      CTS decreased both water droplet contact angle from 124.79 degrees  to 43.14
      degrees  in random and 110.87 degrees  to 33.49 degrees  in aligned PHB/CTS
      fibrous scaffold. Moreover, alignment of fibers causes tremendous increase in
      hydrophilicity of fibrous PHB/CTS substrate. Tensile strength increased from 6.41
      MPa for random to 8.73 MPa for aligned PHB/CTS 85:15. Conclusions: Our results
      indicated that aligned PHB/CTS 85:15 nanofibers are the desired scaffold than the
      random PHB/CTS nanofibers for application in nerve tissue regeneration.

PMID- 29657930
TI  - Establishment and Development of the First Biobank of Inflammatory Bowel Disease,
      Suspected to Primary Immunodeficiency Diseases in Iran.
AB  - Background: Inflammatory bowel disease (IBD) might be an immunodeficiency rather
      than an excessive inflammatory reaction. IBD, suspected to primary
      immunodeficiency diseases biobank (IBDSPIDB) as a resource for researches can
      help improve the prevention, diagnosis, and illness treatment and the health
      promotion throughout the society. Therefore, we launched the biobank of IBDSPID
      for the first time in Iran. Materials and Methods: This study was designed to
      provide the IBDSPIDB to have a high-quality DNA, RNA, and cDNA. Among of 365
      patients, 39 have inclusion criteria that were as below: (1) IBD diagnosis before
      5 years of age. (2) Resistance to conventional therapy of IBD. (3) Severe IBD.
      (4) Signs of SPID (including ear infections or pneumonia or recurrent sinus
      within the 1-year period; failure to thrive; poor response to the prolonged use
      of antibiotics; persistent thrush or skin abscesses; or a family history of PID).
      Results: Out of 39 patients, 51.3% were males. The mean age was 32.92 +/- 15.90
      years old. Ulcerative colitis (79.5%) was more than Crohn's disease. The majority
      of patients (50.0%) had severe IBDSPID. Resistance to drugs and consanguinity was
      12.9% and 47.4%, respectively. Age at onset in 65.8% of patients was after 17
      years old. Patients with autoimmune, allergy, and immunodeficiency disease
      history were 33.3%, 33.3%, and 10.36%, respectively. RNA and cDNA yields large
      quantities of high-quality DNA obtained and stored. Conclusion: Our biobank would
      be valuable for future genetic and molecular study to be more about the relation
      between IBD and PID.

PMID- 29657932
TI  - Normative Ulnar Nerve Conduction Study: Comparison of Two Measurement Methods.
AB  - Background: Given the high prevalence rate of ulnar neuropathy and importance of
      its proper management, to have a baseline information about the normative value
      of motor nerve conduction of first dorsal interosseous (FDI) muscle and abductor
      digiti minimi muscle (ADM) and their differences as well as their relation with
      different demographic characteristics of our population, we aimed to determine
      and compare the mean value of motor conduction velocity of FDI and ADM at forearm
      and across the elbow among the normal population. Materials and Methods: In this
      cross-sectional study, healthy participants were enrolled in the study. Ulnar
      nerve motor nerve conduction velocity (MNCV) was recorded from the ADM and the
      FDI at forearm and across the elbow. Mean MNCV of the ulnar nerve recorded from
      ADM and FDI was compared. In addition, MNCV of the ulnar nerve measured at the
      forearm and across the elbow was compared also. Results: During this study, 165
      healthy volunteers selected and participated in the study. Mean of ulnar nerve
      MNCV for ADM was significantly lower than FDI, both at forearm and across the
      elbow (P < 0.001). Mean of ulnar nerve MNCV was significantly lower at forearm
      comparing than elbow level for both ADM and FDI (P < 0.001). Conclusion: The
      findings of the current study provide us a baseline data regarding the normative
      mean value of ulnar nerve MNCV in different locations, which could be used for
      providing an appropriate diagnostic protocol for ulnar nerve neuropathy. However,
      further studies among patients suspected with ulnar nerve neuropathy are needed.

PMID- 29657931
TI  - Evaluation of Seizure Frequency Distribution in Epileptic Patients with Normal
      and Abnormal Electroencephalogram in Al-Zahra Hospital of Isfahan.
AB  - Background: Epilepsy is a chronic neurological disorder characterized by seizure
      recurrence in patients. Electroencephalogram (EEG) has a diagnostic and
      prognostic role in the management of patients. Studies have shown a significant
      relation between seizure recurrence and abnormal EEG in newly diagnosed epileptic
      patients, and people with first episode of unprovoked seizure. The aim of this
      study is to evaluate seizure frequency in chronic epileptic patients on drug
      therapy based on normal or abnormal EEG. Materials and Methods: This prospective
      cohort study examined seizure recurrence in 59 epileptic patients (50.8%
      generalized, 49.2% focal) with normal and abnormal EEG. Data were recorded in
      patient medical file, and patients were followed by telephone call or visiting by
      neurologist. Results: In this study, 59 patients with a mean age of 29.58 +/-
      10.37 years were assessed that 42.4% of them were males and 57.6% were females.
      Seizure frequency in patient with specific abnormal EEG was significantly more
      than other patients (specific abnormal: 78.9%, nonspecific abnormal: 45.5%, and
      normal: 31%, P = 0.005). Seizure recurrence in patients on polytherapy was
      significantly higher than others (polytherapy: 76.9% and monotherapy: 27.3%, P <
      0.001). In patient with abnormal imaging seizure, frequency was more than other
      patients which was nearly significant (P = 0.054). Conclusion: Abnormal EEG and
      number of anticonvulsant drugs have a role in seizure recurrence in epileptic
      patients.

PMID- 29657933
TI  - Relationship between Height of Ethmoid Skull Base and Length of Lateral Lamella
      by Sectional Coronal Computed Tomography Scan before Endoscopic Sinus Surgery.
AB  - Background: Damage to ethmoid skull base (ESB) and lateral lamella (LL) during
      endoscopic sinus surgery (ESS) causes penetration into the brain. This study is
      aimed to determine the relationship between the height of ESB and length of LL by
      sectional coronal computed tomography (CT) scans before ESS. Materials and
      Methods: In a cross-sectional study, 100 patients admitted to ENT clinic of Al
      Zahra Hospital, filled the consents regarding the use of CT scan stereotype. Each
      stereotype was evaluated and using the software on two sides the height of ESB
      and the length of LL were measured, investigated and recorded. Next, the maximum
      and minimum height and length in the two sides was measured, and its mean
      calculated. Then, the relationship between the length of LL and the height of ESB
      was investigated. Results: There was a direct correlation, with the rate of 0.25
      between the length of right LL and height of right ESB that was significant
      according to Pearson test (P = 0.013). Also, the rate of correlation between the
      left LL and height of left ESB was 0.15 that was not significant according to
      Pearson test (P = 0.15). Conclusion: Based on this study there was a direct
      correlation between height of the right ESB and the length of LL, but this
      correlation is very low, about 0.25 and even this correlation was lower in the
      case of left, about 0.15, which both of them are not significant. This may be due
      to other affecting factors, such as length, slope and angle of fovea ethmoidallis
      from the horizontal line.

PMID- 29657934
TI  - Comparison of Wound Tape and Suture Wounds on Traumatic Wounds' Scar.
AB  - Background: Several methods have been used in wound closure for traumatic wounds,
      but it is not clear that which of these methods has more safety and efficacy.
      This study aimed to compare scar width due to standard and current treatments in
      wound repair by suturing and method of wound restoration using wound tape in
      patients with traumatic ulcers. Materials and Methods: This randomized clinical
      trial was done in ninety patients with wounds in the facial area. They were
      divided randomly into two groups of 45. The wounds in the first group were
      sutured, and wound tapes were used to wound closure in the second group. After 2
      months, length and width of scar and results of life-size photography were
      recorded in a list, especially prepared for this purpose. Results: The mean age
      of the patients was 22.7 +/- 12.9 years with 46 males (56.1%) and 36 females
      (43.9%). After 2 months, scars width in suture wound group was 2.9 mm and in
      wound tape group was 2.5 mm, with no statistically significant difference (P =
      0.07). In patients with wound length of >20 mm, scars width was similar between
      groups and no significant differences was noted (P = 0.27), but in patients with
      wound length of <20 mm, scars width in wound tape group was significantly less
      than suture wound group (1.7 vs. 2.5 mm, respectively, P = 0.01). Wound
      complications were not significantly different between the two groups.
      Conclusion: Findings revealed that scar formation in wounds lower than 20 mm
      treated using wound tape was lower than suture, but for wounds between 20 and 50
      mm were similar between wound tape and suture.

PMID- 29657935
TI  - A Large Primary Subcutaneous Hydatid Cyst in Proximal Thigh: An Unusual
      Localization.
AB  - Primary muscular hydatidosis is a very rare condition with an incidence of 1%-4%
      in endemic regions. This case report describes an unusual location of hydatid
      cyst in the sartorius muscle and the application of imaging in its preoperative
      diagnosis, choosing a treatment strategy, and monitoring.

PMID- 29657936
TI  - Cellular Therapy for Chronic Traumatic Brachial Plexus Injury.
AB  - Cellular therapy is being actively pursued as a therapeutic modality in many of
      the neurological diseases. A variety of stem cells from diverse sources have been
      studied in detail and have been shown to exhibit angiogenetic and
      immunomodulatory properties in addition to other neuroprotective effects.
      Published clinical data have shown bone marrow mononuclear cell (BMMNC) injection
      in neurological disorders is safe and possesses regenerative potential. We
      illustrate a case of 27-year-old male with traumatic brachial plexus injury,
      administered with autologous BMMNCs intrathecally and intramuscularly, followed
      by multidisciplinary rehabilitation. At the follow-up assessment of 3 and 7
      months after first cell transplantation, improvements were recorded in muscle
      strength and movements. Electromyography (EMG) performed after the intervention
      showed a response in biceps and deltoid muscles suggesting the process of
      reinnervation at the site of injury. In view of the improvements observed after
      the treatment, the patient underwent second cell transplantation 8 months after
      the first transplantation. Muscle wasting had completely stopped with an increase
      in the muscle girth. No adverse effects were noted. Improvements were maintained
      for 4 years. A comprehensive randomized study for this type of injury is needed
      to establish the therapeutic benefits of cellular therapy.

PMID- 29657937
TI  - The Role of Angiotensin II Infusion on the Baroreflex Sensitivity and Renal
      Function in Intact and Bilateral Renal Denervation Rats.
AB  - Background: The role of renin-angiotensin system (RAS) in communication between
      renal system and cardiovascular system is extremely important. Baroreflex
      sensitivity (BRS) index defines as heart rate (HR) alteration versus mean
      arterial pressure (MAP) change ratio . Sympathetic nerve is arm of the
      baroreflexes and any change in its activity will lead to change in the BRS. The
      role of angiotensin II (Ang II) infusion in systemic circulation accompanied with
      bilateral renal denervation (RDN) on BRS index and renal function was studied.
      Materials and Methods: Seventy-two male and female Wistar rats in 12 groups were
      anesthetized and catheterized. The alteration of MAP and HR responses to
      phenylephrine infusion compared to control groups was determined in bilateral RDN
      rats subjected to treat with Ang II (300 or 1000 ng/kg/min) administration.
      Results: The BRS index was elevated in Ang II-treated non-RDN (normal) male rats
      gradually and dose dependently (P < 0.05), while this index was significantly
      different when compared with RDN male rats (P < 0.05). Accordingly, the BRS index
      was significantly lower in RDN than non-RDN male rats, and such observation was
      not observed in female rats. The creatinine clearance (insignificantly) and urine
      flow (significantly; P < 0.05) were decreased in both non-RDN and RDN male and
      female rats treated with Ang II. In RDN model, the serum nitrite levels were
      decreased in male and increased in female by Ang II infusion when compared with
      vehicle infusion. Conclusion: The Ang II infusion could increase the BRS index in
      non-RDN (normal) male rats which is significantly greater than BRS index in RDN
      rats.

PMID- 29657938
TI  - Formulation of Herbal Gel of Antirrhinum majus Extract and Evaluation of its Anti
      Propionibacterium acne Effects.
AB  - Background: Antirrhinum majus contains aurone with excellent antibacterial and
      antifungal activities. In addition, visible light activates the endogenous
      porphyrins of Propionibacterium acne, which results in bacterial death.
      Therefore, considering the above-mentioned facts, the aim of the present study
      was to prepare a topical herbal gel of A. majus hydroalcoholic extract and to
      evaluate its antiacne effects with or without blue light combination as an
      activator of the porphyrins. Materials and Methods: Antibacterial activity of the
      shoot or petal extracts was evaluated by disc diffusion method and the minimum
      inhibitory concentration (MIC) was calculated. Various gel formulations were
      developed by the Experimental Design software. The obtained gel formulations were
      prepared and tested for pharmaceutical parameters including organoleptic
      features, pH, viscosity, drug content, and release studies. Finally, the
      antibacterial activity was evaluated against (P. acnes) with or without blue
      light. Results: The MIC of the extracts showed to be 0.25 MUg/ml. Evaluation of
      the gel formulation showed acceptable properties of the best formulation in
      comparison to a gel in the market. Pharmaceutical parameters were also in
      accordance with the standard parameters of the marketed gel. Furthermore,
      statistical analyses showed significant antibacterial effect for gel when
      compared to negative control. However, combination of blue light with gel did not
      show any significant difference on the observed antibacterial effect. Conclusion:
      Because of the statistically significant in vitro antiacne effects of the
      formulated gel, further clinical studies for evaluation of the healing effects of
      the prepared gel formulation on acne lesions must be performed.

PMID- 29657939
TI  - Cisplatin Alters Sodium Excretion and Renal Clearance in Rats: Gender and Drug
      Dose Related.
AB  - Background: Nephrotoxicity is one of the side effects of cisplatin (CP) therapy
      which is gender related. CP disturbs renal function through glomerular filtration
      rate and electrolytes transport disturbances. This study was designed to compare
      some markers related to renal function in two protocols of CP treatment in rats.
      Materials and Methods: Male and female rats were subjected to receive single
      (treat 1; 7.5 mg/kg) and continues doses (treat 2; 3 mg/kg/day for 5 days) of CP,
      and the measurements were compared with control animals. Results: The serum level
      of blood urea nitrogen (BUN) and creatinine (Cr), and Cr-clearance, kidney tissue
      damage score, kidney weight, body weight change, and Na excretion was altered
      significantly (P < 0.05) in animals treated with continuous dose of CP (treat 2),
      while alteration of BUN and Cr was gender related. The kidney levels of
      malondialdehyde and nitrite were significantly different between male and female
      in two protocols of treatments. Conclusion: Renal function after CP therapy
      alters in rats' gender dependently, and it is related to protocol of treatment.

PMID- 29657940
TI  - Levofloxacin-containing versus Clarithromycin-containing Therapy for Helicobacter
      pylori Eradication: A Prospective Randomized Controlled Clinical Trial.
AB  - Background: This study evaluated the clinical efficacy and tolerability of a 14
      day course of bismuth-based quadruple therapy including tinidazole and
      levofloxacin in compare to a 14-day bismuth-based quadruple therapy including
      clarithromycin as first-line treatment for Helicobacter pylori infection in
      Iranian adults. Materials and Methods: The study was a prospective, parallel
      group, randomized controlled, clinical trial that conducted on 150 patients with
      H. pylori infection. Patients were randomly assigned to the two groups as
      follows: first group received pantoprazole 40 mg, bismuth subcitrate 240 mg,
      amoxicillin 1 g, and clarithromycin 500 mg (PBAC group), and other group received
      pantoprazole 40 mg, bismuth subcitrate 240 mg, amoxicillin 1 g, tinidazole 500 mg
      for 7 days, followed by levofloxacin 500 mg for the second 7 days (PBATL group).
      Main outcomes were eradication rate, tolerance of treatment, and dyspepsia
      severity. Results: The eradication rates for PBAC regimen was 81.1% (95%
      confidence interval [CI]: 71.9-90.2) and for PBATL regimen was 70.8% (95% CI:
      60.1-81.6), which was not significantly different (P = 0.147). Tolerance of
      treatment was similar between groups. The median of severity of dyspeptic after
      treatment in PBAC group was 10 [9-14.75], which was similar to PBATL group 10 [9
      13.5] (P = 0.690). Conclusion: There is no significant difference between PBAC
      and PBATL regimen, and efficacy was similar in both groups. The overall rate of
      treatment failure suggests that up to 18%-30% of patients will fail bismuth-based
      quadruple therapy and require retreatment for the infection.

PMID- 29657941
TI  - Investigation of Frequency Distribution of Breast Imaging Reporting and Data
      System (BIRADS) Classification and Epidemiological Factors Related to Breast
      Cancer in Iran: A 7-year Study (2010-2016).
AB  - Background: The first cause of women mortality due to cancer is breast cancer.
      Mammography plays a central part in early detection of breast cancers. The
      screening methods can play a major role to reduce the morbidity and mortality
      rate due to this malignancy. We sought the basic data in this study on our
      population because knowing about the baseline data is apt and vital. Materials
      and Methods: In this study, data were collected from a questionnaire, contained
      baseline bio data information, and mammographic imaging of the patients came
      during 7 years. Breast imaging reporting and data system (BIRADS) score, breast
      composition, presence of axillary lymph nodes, microcalcifications, and other
      incidental positive findings were determined by a radiologist and analysis was
      performed by SPSS package. Results: The most common indication for mammography
      was annual screening. The mean age of participants to the study was 55 +/- 7.9
      years. The majority (80%) of the patients with known breast cancer (BIRADS 6) had
      the extremely dense breast. The most common incidental findings in mammogram
      studies were focal asymmetry, architectural distortion, intramammary lymph node
      and accessory breasts, respectively. Conclusion: The frequency distribution of
      BIRADS classification in our society was clarified. It seems that the breast
      cancer risk is higher in women with dense breasts. Architectural distortion was
      also correlated to BIRADS score.

PMID- 29657942
TI  - Music Therapy and Social Skills in Autism: Underlying Biological Mechanisms.

PMID- 29657943
TI  - The Relationship between Tuberculosis and Lung Cancer.

PMID- 29657944
TI  - Driving Outcomes among Older Adults: A Systematic Review on Racial and Ethnic
      Differences over 20 Years.
AB  - The population of older adults (aged 65 years and older) in the United States
      will become more racially and ethnically diverse in the next three decades.
      Additionally, the growth of the aging population will come with an expansion in
      the number of older drivers and an increased prevalence of chronic neurological
      conditions. A major gap in the aging literature is an almost exclusive focus on
      homogenous, non-Hispanic white samples of older adults. It is unclear if this
      extends to the driving literature. A systematic review of SCOPUS, PubMed, CINAHL
      Plus, and Web of Science examined articles on driving and racial/ethnic
      differences among older adults. Eighteen studies met inclusion criteria and their
      results indicate that racial and ethnic minorities face a greater risk for
      driving reduction, mobility restriction, and driving cessation. The majority of
      studies compared African Americans to non-Hispanic whites but only examined race
      as a covariate. Only four studies explicitly examined racial/ethnic differences.
      Future research in aging and driving research needs to be more inclusive and
      actively involve different racial/ethnic groups in study design and analysis.

PMID- 29657945
TI  - THE ROLE OF PROTEIN CHAPERONES IN THE SURVIVAL FROM ANTHRACYCLINE-INDUCED
      OXIDATIVE STRESS IN SACCHAROMYCES CEREVISIAE.
AB  - Several S. cerevisiae deletion strains involving heat-shock response factors were
      among the most sensitive mutants identified in a previous genetic screen for
      doxorubicin hypersensitivity. These strains included ydj1Delta, ssz1Delta and
      zuo1Delta mutants. In addition, new1Delta, whose function was unknown, also
      displayed significant sensitivity to anthracyclines. We further investigated the
      basis for the sensitivity of these mutants. We determined that heat-shock could
      partially rescue the sensitivity of the strains to doxorubicin, including the
      homologous recombination mutant rad52Delta, which is sensitive to doxorubicin
      mediated DNA double strand breaks (DSBs). However, none of the heat-shock
      response mutants were sensitive to DSBs, but were highly sensitive to reactive
      oxygen species (ROS) generated by quinone-ring-containing agents, such as
      anthracyclines and menadione. A fluorescent-based assay indicates that
      doxorubicin causes protein aggregation. Interestingly, the disaggregase mutant
      hsp104Delta is not sensitive to anthracyclines or menadione suggesting that
      Hsp104p does not play a role in disaggregating doxorubicin-induced protein
      aggregates. However New1p, which has been recently shown to be a novel
      disaggregase, is essential for cell viability after exposure to anthracyclines
      and menadione and it is not involved in thermotolerance. Our data suggest that in
      S. cerevisiae, doxorubicin produces protein aggregation through ROS and requires
      Ydj1p and New1p for resolution.

PMID- 29657946
TI  - Too Cold to Clot? Does Intraoperative Hypothermia Contribute to Bleeding After
      Aortic Surgery?
AB  - Background: We determined the impact of intraoperative hypothermia on
      postoperative bleeding after thoracic aortic surgery. Methods: We retrospectively
      analyzed 98 consecutive patients who underwent aortic surgery with deep
      hypothermic circulatory arrest between 2010 and 2014. We evaluated lowest
      temperature, absolute decrease in temperature, and rewarming rate. Univariate and
      multivariate regression were used to determine relationships between temperature,
      clinical characteristics, and measures of postoperative bleeding. Results: The
      mean age of patients was 60.5 +/- 15.1 years, with 64.3% male and 60% Caucasian.
      The lowest temperatures recorded were 13.5 +/- 4.6 degrees C at the bypass
      circuit. Change in hematocrit was associated with ethnicity, preoperative
      hematocrit, and rewarming rate. Chest tube output was associated with body mass
      index, preoperative platelet count, prior cardiac surgery, cardiopulmonary bypass
      (CPB) duration, intraoperative blood product transfusion, lowest surface
      temperature, and change in surface temperature. Postoperative packed red blood
      cell transfusion was associated with ejection fraction, chronic obstructive
      pulmonary disease (COPD), platelet count, partial thromboplastin time, CPB
      duration, and lowest blood temperature. Fresh frozen plasma transfusion
      correlated with COPD, CPB duration, and final blood temperature. Platelet
      transfusion correlated with body mass index and preoperative platelet count.
      Unplanned reoperation for bleeding was associated with final temperature and
      change in temperature. Conclusion: We found no consistent associations between
      intraoperative temperature and indicators of bleeding. Intraoperative cooling
      strategies should be based on optimal end-organ protection rather than fear of
      postoperative bleeding; rewarming strategies may ameliorate the risk of
      coagulopathy.

PMID- 29657947
TI  - Modifiable Risk Factors for Early Mortality in Low-Risk Penn Class Aa Acute Type
      A Aortic Dissection Patients - A Descriptive Study.
AB  - Background: Acute Type A aortic dissection (ATAAD) without end-organ or
      generalized ischemia is Penn class Aa and considered low-risk. Nevertheless,
      surgical mortality can be considerable in this subgroup and may be related to
      modifiable factors. The objective of this study was to analyze 30-day mortality
      among ATAAD Penn class Aa patients with special reference to modifiable
      perioperative factors. Methods: Among all patients operated for ATAAD from 1990
      to 2010, all Penn class Aa patients dying within 30 days were included in a
      retrospective descriptive study. Pre- and intraoperative variables related to 30
      day mortality were retrieved from medical records and analyzed according to
      avoidable or modifiable errors such as initial misdiagnosis, preoperative delay,
      adverse events, and forced and unforced additional procedures. Results: Overall
      30-day mortality was 13% (31/235). Intraoperative death occurred in 32% (10/31)
      of patients. Among patients not dying intraoperatively, stroke was the most
      common complication (48%) and cause of death overall, followed by reoperation for
      bleeding (33%), respiratory failure (24%), and renal failure (14%). Preoperative
      errors were detected in 48% of patients; one-third had initial misdiagnosis
      and/or diagnostic delay >= 24 hours. Intraoperative error(s) was noted in 74% of
      patients, mainly involving adverse event(s), forced additional procedures, and
      assisted bleeding control, with each affecting approximately 45% of patients.
      Conclusion: Modifiable errors in pre- and intraoperative management are not
      uncommon among Penn class Aa patients and may contribute to 30-day mortality.
      Efforts should be made to mitigate the effects of modifiable factors to reduce
      early mortality in low-risk ATAAD.

PMID- 29657948
TI  - Early Results of the PETTICOAT Technique for the Management of Acute Type A
      Aortic Dissection.
AB  - Conventional surgical techniques for acute Type A aortic dissection (ATAAD)
      generally fail to address residual dissection in the descending aorta. The
      persistence of a false lumen is associated with visceral malperfusion in the
      acute setting and adverse aortic remodeling in the chronic setting. Hybrid aortic
      arch repair techniques may improve perioperative and long-term mortality by
      expanding the true lumen and obliterating the false lumen. However, there is a
      limit to the extent of aortic coverage due to the concomitant risk of spinal cord
      ischemia. In Type B dissection, the PETTICOAT (Provisional Extension To Induce
      Complete Attachment) technique, which entails stent graft coverage of the primary
      intimal tear followed by bare metal stent placement distally, may improve true
      lumen caliber and promote false lumen thrombosis without increasing the risk of
      spinal cord ischemia, as intercostal branches remain perfused through the bare
      metal stents. The technique of hybrid arch with surgical creation of a Dacron
      landing zone covering a stent graft in the proximal descending aorta and bare
      metal stents in the thoraco-abdominal aorta is a promising concept in the
      treatment of ATAAD.

PMID- 29657949
TI  - Page for the General Public.

PMID- 29657950
TI  - List of Upcoming Meetings.

PMID- 29657951
TI  - Distribution of Thoracic Aortic Calcifications in Patients Undergoing Coronary
      Artery Bypass Grafting.
AB  - Background: In procedures involving surgical maneuvers such as cannulation,
      clamping, or proximal anastomosis where aortic manipulation is inevitable, a
      preliminary assessment of atherosclerotic plaques bears clinical significance. In
      the present study, our aim was to evaluate the frequency and distribution of
      aortic calcifications in patients undergoing coronary artery bypass grafting
      (CABG) surgery to propose a morphological classification system. Methods: A total
      of 443 consecutive patients with coronary artery disease were included in this
      study. Preoperative non-contrast enhanced computed tomography images, in-hospital
      follow-up data, and patient characteristics were retrospectively evaluated.
      Results: Whereas 33% of patients had no calcifications at any site in the aorta,
      7.9%, 75.4%, and 16.7% had calcifications in the ascending aorta, aortic arch,
      and descending aorta, respectively. Focal small calcifications were the most
      common type of lesions in the ascending aorta (3.9%), whereas 9 patients (1.4%)
      had porcelain ascending aorta. We defined four types of patients with increasing
      severity and extent of calcifications. Conclusions: Based on the frequency and
      distribution of calcifications in the thoracic aorta, we propose a classification
      system from least to most severe for coronary artery disease patients who are
      candidates for CABG.

PMID- 29657952
TI  - Surgical Treatment of Annuloaortic Ectasia - Replace or Repair?
AB  - Background: Patients with annuloaortic ectasia may be surgically treated with
      modified Bentall or David I valve-sparing procedures. Here, we compared the long
      term results of these procedures. Methods: A total of 181 patients with
      annuloaortic ectasia underwent modified Bentall (102 patients, Group 1) or David
      I (79 patients, Group 2) procedures from 1994 to 2015. Mean age was 62 +/- 11
      years in Group 1 and 64 +/- 16 years in Group 2. Group 1 patients were in poorer
      health, with a lower ejection fraction and higher functional class. Results:
      Early mortality was 3% in Group 1 and 2.5% in Group 2. Patients undergoing a
      modified Bentall procedure had a higher incidence of thromboembolism and
      hemorrhage, whereas those undergoing a David I procedure had a higher incidence
      of endocarditis. Actuarial survival was 70 +/- 6% at 15 years in Group 1 and 84
      +/- 7% at 10 years in Group 2. Actuarial freedom from reoperation was 97 +/- 2%
      at 15 years in Group 1 and 84 +/- 7% at 10 years in Group 2. In Group 2, freedom
      from procedure-related reoperations was 98 +/- 2% at 10 years. At last follow-up,
      no cases of moderate or severe aortic regurgitation were observed. Conclusions:
      The modified Bentall and David I procedures showed excellent early and late
      results. The modified Bentall procedure with a mechanical conduit was associated
      with thromboembolic and hemorrhagic complications, whereas the David I procedure
      was associated with unexplained occurrences of endocarditis. Thus, the David I
      procedure appears to be safe, reproducible, and capable of achieving stable
      aortic valve repair and is therefore our currently preferred solution for
      patients with annuloaortic ectasia. However, the much shorter follow-up for David
      I patients limits the strength of our comparison between the two techniques.

PMID- 29657953
TI  - Factors Affecting Follow-Up Compliance in Patients After Endovascular Aneurysm
      Repair.
AB  - Objective: The purpose of this study was to evaluate potential factors affecting
      patient non-compliance after endovascular aneurysm repair. Method: We performed a
      retrospective review of patients undergoing elective or emergency endovascular
      repair for thoracic, abdominal aorta, or iliac artery aneurysm at a single
      institution from November 2007 to March 2014. Compliance to follow-up at 1, 6,
      and 12 months was assessed. Factors evaluated included patient demographics, size
      of aneurysm, distance between the patient's residence and outpatient clinic,
      urgency of surgery, and time of year in which the follow-up visits were
      scheduled. Results: During the study period, 205 patients (75% male and 25%
      female) fulfilled the inclusion criteria. One-month mortality was 1.1% for
      elective procedures and 16.1% for emergency procedures (p = 0.001). Overall
      mortality at 12 months was 6.3% and 32.3% for elective and emergency procedures,
      respectively (p = 0.0002). Highest compliance was observed at 1 month, with 184
      patients (93%) attending. A significant decrease was seen at 6 (n = 102, 54%) and
      12 (n = 89, 48%) months. At the 12-month mark, a larger proportion of minority
      patients were non-compliant compared with Caucasian patients. Confounders for non
      compliance were analyzed using multivariate analysis, and statistical
      significance was found for widowed marital status (p = 0.008), travel distance
      >25 miles to the outpatient clinic (p = 0.032), and emergency repair of aneurysms
      (p = 0.022). Conclusion: Despite emphasizing the importance of follow-up after
      endovascular aortic procedures, almost half of the treated patients were non
      compliant. Our study identified travel distance, marital status, and urgency of
      surgery as factors that may affect patients' compliance to scheduled follow-up
      visits.

PMID- 29657954
TI  - Automated Predictive Big Data Analytics Using Ontology Based Semantics.
AB  - Predictive analytics in the big data era is taking on an ever increasingly
      important role. Issues related to choice on modeling technique, estimation
      procedure (or algorithm) and efficient execution can present significant
      challenges. For example, selection of appropriate and optimal models for big data
      analytics often requires careful investigation and considerable expertise which
      might not always be readily available. In this paper, we propose to use semantic
      technology to assist data analysts and data scientists in selecting appropriate
      modeling techniques and building specific models as well as the rationale for the
      techniques and models selected. To formally describe the modeling techniques,
      models and results, we developed the Analytics Ontology that supports inferencing
      for semi-automated model selection. The SCALATION framework, which currently
      supports over thirty modeling techniques for predictive big data analytics is
      used as a testbed for evaluating the use of semantic technology.

PMID- 29657955
TI  - Challenges Across the HIV Care Continuum for Patients With HIV/1 TB Co-infection
      in Atlanta, GA.
AB  - Background: Antiretroviral therapy (ART) for persons with HIV infection prevents
      tuberculosis (TB) disease. Additionally, sequential ART after initiation of TB
      treatment improves outcomes. We examined ART use, retention in care, and viral
      suppression (VS) before, during, and 3 years following TB treatment for an inner
      city cohort in the United States. Methods: Retrospective cohort study among
      persons treated for culture-confirmed TB between 2008 and 2015 at an inner-city
      hospital. Results: Among 274 persons with culture-confirmed TB, 96 (35%) had HIV
      co-infection, including 23 (24%) new HIV diagnoses and 73 (76%) previous
      diagnoses. Among those with known HIV prior to TB, the median time of known HIV
      was 6 years, and only 10 (14%) were on ART at the time of TB diagnosis. The
      median CD4 at TB diagnosis was 87 cells/uL. Seventy-four (81%) patients received
      ART during treatment for TB, and 47 (52%) has VS at the end of TB treatment. Only
      32% of patients had continuous VS 3 years after completing TB treatment. There
      were 3 TB recurrences and 3 deaths post-TB treatment; none of these patients had
      retention or VS after TB treatment. Conclusions: Among persons with active TB co
      infected with HIV, we found that the majority had known HIV and were not on ART
      prior to TB diagnosis, and retention in care and VS post-TB treatment were very
      low. Strengthening the HIV care continuum is needed to improve HIV outcomes and
      further reduce rates of active TB/HIV co-infection in our and similar settings.

PMID- 29657956
TI  - Results of a Hepatitis C Virus Screening Program of the 1945-1965 Birth Cohort in
      a Large Emergency Department in New Jersey.
AB  - Background: Persons born between 1945 and 1965 account for an estimated 81% of
      those infected with hepatitis C virus (HCV) in the United States. However, up to
      60% remain undiagnosed. Prior studies have reported HCV screening results from
      large urban emergency departments. Methods: This is a retrospective cohort study
      of patients in the 1945-1965 birth cohort tested for HCV in a large emergency
      department (ED) in New Jersey from June 1, 2016, through December 31, 2016. The
      purpose was to report HCV antibody and viral load results of this testing program
      located in a small urban/suburban area and to analyze specific characteristics
      associated with positive results, such as race/ethnicity and insurance status.
      Descriptive statistics were performed, and, using a multivariate logistic
      regression model, adjusted odds ratios and 95% confidence intervals were
      calculated. Results: A total of 3046 patients were screened: 55.8% were white,
      and 17.9% were black; 52.1% had private insurance, 33.4% Medicare, 3.9% Medicaid.
      One hundred ninety-two were antibody positive (6.3%). Of 167 with HCV viral load
      testing results, 43% had a positive viral load. On multivariate analysis, black
      race and Medicaid were independently associated with a positive HCV viral load.
      Conclusions: HCV antibody seropositivity was above 6% and twice as high as the
      Centers for Disease Control and Prevention estimated prevalence in this birth
      cohort. These results indicate that EDs outside of large urban cities are also
      important sites for routine HCV screening. Other findings of interest include 43%
      with chronic HCV infection and the persistent association between black race and
      positive HCV viral load even when adjusted for insurance status.

PMID- 29657957
TI  - The Effect of Deep Brain Stimulation Therapy on Fear-Related Capture of Attention
      in Parkinson's Disease and Essential Tremor: A Comparison to Healthy Individuals.
AB  - In addition to motor symptoms, Parkinson's disease (PD) involves significant non
      motor sequelae, including disruptions in cognitive and emotional processing. Fear
      recognition appears to be affected both by the course of the disease and by a
      common interventional therapy, deep brain stimulation of the subthalamic nucleus
      (STN-DBS). Here, we examined if these effects extend to other aspects of
      emotional processing, such as attentional capture by negative emotional stimuli.
      Performance on an emotional attentional blink (EAB) paradigm, a common paradigm
      used to study emotional capture of attention, was examined in a cohort of
      individuals with PD, both on and off STN-DBS therapy (n=20). To contrast effects
      of healthy aging and other movement disorder and DBS targets, we also examined
      performance in a healthy elderly (n=20) and young (n=18) sample on the same task,
      and a sample diagnosed with Essential Tremor (ET) undergoing therapeutic deep
      brain stimulation of the ventral-intermediate nucleus (VIM-DBS, n=18). All four
      groups showed a robust attentional capture of emotional stimuli, irrespective of
      aging processes, movement disorder diagnosis, or stimulation. PD patients on
      average had overall worse performance, but this decrement in performance was not
      related to the emotional capture of attention. PD patients exhibited a robust
      EAB, indicating that the ability of emotion to direct attention remains intact in
      PD. Congruent with other recent data, these findings suggest that fear
      recognition deficits in PD may instead reflect a highly specific problem in
      recognition, rather than a general deficit in emotional processing of fearful
      stimuli.

PMID- 29657958
TI  - Soft-mode driven polarity reversal in ferroelectrics mapped by ultrafast x-ray
      diffraction.
AB  - Quantum theory has linked microscopic currents and macroscopic polarizations of
      ferroelectrics, but the interplay of lattice excitations and charge dynamics on
      atomic length and time scales is an open problem. Upon phonon excitation in the
      prototypical ferroelectric ammonium sulfate [(NH4)2SO4], we determine transient
      charge density maps by femtosecond x-ray diffraction. A newly discovered low
      frequency-mode with a 3 ps period and sub-picometer amplitudes induces periodic
      charge relocations over some 100 pm, a hallmark of soft-mode behavior. The
      transient charge density allows for deriving the macroscopic polarization,
      showing a periodic reversal of polarity.

PMID- 29657959
TI  - Improvement of Early Antenatal Care Initiation: The Effects of Training Local
      Health Volunteers in the Community.
AB  - Background: Although antenatal care (ANC) coverage has been increasing in low-
      and middle-income countries, the adherence to the ANC initiation standards at
      gestational age <12 weeks was inadequate including Thailand. The study aimed to
      improve the rate of early ANC initiation by training the existing local health
      volunteers (LHVs) in 3 southernmost provinces of Thailand. Methods: A clustered
      nonrandomized intervention study was conducted from November 2012 to February
      2014. One district of each province was selected to be the study intervention
      districts for that province. A total of 124 LHVs in the intervention districts
      participated in the knowledge-counseling intervention. It was organized as half
      day workshop using 2 training modules each comprising a 30-minute lecture
      followed by counseling practice in pairs for 1 hour. Outcome was the rate of
      early ANC initiation among women giving birth, and its association with
      intervention, meeting an LHV, and months after training was analyzed. Results: Of
      6677 women, 3178 and 3499 women were in the control and intervention groups,
      respectively. Rates of early ANC were significantly improved after the
      intervention (adjusted odds ratio [OR]: 1.29, 95% confidence interval [CI]: 1.17
      1.43, P < .001) and meeting an LHV (adjusted OR: 2.06, 95% CI: 1.86-2.29, P <
      .001), but lower at 6 months after training (adjusted OR: 0.76, 95% CI: 0.60
      0.96, P = .002). Almost all women (99.7%) in the intervention group who met an
      LHV reported that they were encouraged to attend early ANC. Conclusion: Training
      LHVs in communities by knowledge-counseling intervention significantly improved
      early ANC initiation, but the magnitude of change was still limited.

PMID- 29657960
TI  - Early Life Stress Alters Adult Inflammatory Responses in a Mouse Model for
      Depression.
AB  - Increased levels of pro-inflammatory cytokines and hypothalamic pituitary axis
      (HPA) activity are strongly associated with depression. Childhood stress and
      trauma predispose individuals for increased inflammatory tone and major
      depression in later life, suggesting that early life reprogramming of the
      stress/immune axis may be involved in the pathogenesis of depression. In this
      study, we are using a short duration neonatal maternal separation stress (MS)
      paradigm in mice to test if early life stress can impact plasma and brain
      inflammatory tone into adulthood. We use ELISA assays to investigate levels of
      the pro-inflammatory cytokines IL-1beta, IL-2, IL-6 and TNF-alpha, in both plasma
      and brain tissue of mice exposed to MS (STR), their unseparated littermates (LMC)
      and unhandled age matched controls (AMC). Cytokine levels are assessed in male
      and female adult mice with and without a bacterial lipopolysaccharide (LPS)
      induced immune challenge. We present evidence that stress exposure, during the
      first week of life, predisposes both male and female mice for increased
      inflammatory cytokine secretion, peripherally and in brain tissue, upon adult
      exposure to lipopolysaccharide (LPS).

PMID- 29657961
TI  - Reproductive Dysfunction from the Stress of Exercise Training is not Gender
      Specific: The "Exercise-Hypogonadal Male Condition".
AB  - Investigative studies point to participation in exercise training as having
      significant detrimental effects upon reproductive hormonal profiles in men.
      Specifically, men chronically exposed to training for endurance sports exhibit
      persistently reduced basal (resting-state) free and total testosterone
      concentrations without concurrent LH elevations. Men displaying these symptoms
      have been deemed to exhibit the "Exercise-Hypogonadal Male Condition" (EHMC). The
      exact physiological mechanism inducing the reduction of testosterone in these men
      is currently unclear, but is postulated to be a dysfunction within the
      hypothalamic-pituitary-gonadal regulatory axis. The potential exists for the
      reduced testosterone concentrations within EHMC men to be disruptive and
      detrimental to some anabolic-androgenic testosterone-dependent physiological
      processes. Findings, while limited, suggest spermatogenesis problems may exist in
      some cases; thus, infertility risk in such men is a critical concern. Present
      evidence suggests the EHMC condition is limited to men who have been persistently
      involved in chronic endurance exercise training for an extended period of time,
      and thus is not a highly prevalent occurrence. Nevertheless, it is critical that
      endocrinologist and fertility clinicians become more aware of the existence of
      EHMC as a potential problem-diagnosis in their male patients who exercise.

PMID- 29657962
TI  - A Robust Method for Estimating B0 Inhomogeneity Field in the Liver by Mitigating
      Fat Signals and Phase-Wrapping.
AB  - We developed an optimized and robust method to estimate liver B0 field
      inhomogeneity for monitoring and correcting susceptibility-induced geometric
      distortion in magnetic resonance images for precision therapy. A triple-gradient
      echo acquisition was optimized for the whole liver B0 field estimation within a
      single-exhale breath-hold scan on a 3 T scanner. To eliminate chemical-shift
      artifacts, fat signals were chosen in-phase between 2 echoes with an echo time
      difference (DeltaTE) of 2.3 milliseconds. To avoid phase-wrapping, other 2 echoes
      provided a large field dynamic range (1/DeltaTE) to cover the B0 field
      inhomogeneity. In addition, using high parallel imaging factor of 4 and a readout
      bandwidth of 1955 Hz/pixel, an ~18-second acquisition time for breath-held scans
      was achieved. A 2-step, 1-dimensional regularized method for the DeltaB0 field
      map estimation was developed, tested and validated in phantom and patient
      studies. Our method was validated on a water phantom with fat components and air
      pockets; it yielded DeltaB0-field maps that had no chemical-shift and phase
      wrapping artifacts, and it had a <0.5 mm of geometric distortion near the air
      pockets. The DeltaB0-field maps of the patients' abdominal regions were also free
      from phase-wrapping and chemical-shift artifacts. The maximum field inhomogeneity
      was found near the lung-liver interface, up to ~300 Hz, resulting in ~2 mm of
      distortions in anatomical images with a readout-bandwidth of 440 Hz/pixel. The
      field mapping method in the abdominal region is robust; it can be easily
      integrated in clinical workflow for patient-based quality control of magnetic
      resonance imaging geometric integrity.

PMID- 29657963
TI  - Hologenomics: Systems-Level Host Biology.
AB  - The hologenome concept of evolution is a hypothesis explaining host evolution in
      the context of the host microbiomes. As a hypothesis, it needs to be evaluated,
      especially with respect to the extent of fidelity of transgenerational
      coassociation of host and microbial lineages and the relative fitness
      consequences of repeated associations within natural holobiont populations.
      Behavioral ecologists are in a prime position to test these predictions because
      they typically focus on animal phenotypes that are quantifiable, conduct studies
      over multiple generations within natural animal populations, and collect metadata
      on genetic relatedness and relative reproductive success within these
      populations. Regardless of the conclusion on the hologenome concept as an
      evolutionary hypothesis, a hologenomic perspective has applied value as a systems
      level framework for host biology, including in medicine. Specifically, it
      emphasizes investigating the multivarious and dynamic interactions between
      patient genomes and the genomes of their diverse microbiota when attempting to
      elucidate etiologies of complex, noninfectious diseases.

PMID- 29657964
TI  - Vive la Persistence: Engineering Human Microbiomes in the 21st Century.
AB  - I imagine a future in which children grow up with healthy microbial communities.
      Engineering human microbiomes might actually be achievable in the near future, as
      we enter an era of hunting for human-adapted bacterial strains and phages.
      Furthermore, breath metabolites could allow us to track whether a probiotic
      colonizes persistently or a phage has knocked down a microbe of interest. Recent
      successes with probiotics, such as bifidobacteria that can break down human milk
      oligosaccharides, are making a future in which infants are intentionally
      colonized with health-promoting strains seem less unlikely. Viruses that infect
      bacteria, bacteriophages, are also important for human health both because of
      their role in the human microbiome and because of their potential for use in
      phage therapy. Monitoring the outcome of microbiome-focused interventions with
      breath volatile sampling is also on the horizon, which could mean real-time
      tracking of microbial metabolite production. Studies of early life during
      microbiome assembly, when the potential for effective interventions to reduce
      disease risk is greatest, are essential.

PMID- 29657965
TI  - Considering the Lives of Microbes in Microbial Communities.
AB  - Over the last decades, sequencing technologies have transformed our ability to
      investigate the composition and functional capacity of microbial communities.
      Even so, critical questions remain about these complex systems that cannot be
      addressed by the bulk, community-averaged data typically provided by sequencing
      methods. In this Perspective, I propose that future advances in microbiome
      research will emerge from considering "the lives of microbes": we need to create
      methods to explicitly interrogate how microbes exist and interact in native
      setting-like microenvironments. This approach includes developing approaches that
      expose the phenotypic heterogeneity of microbes; exploring the effects of
      coculture cues on cellular differentiation and metabolite production; and
      designing visualization systems that capture features of native microbial
      environments while permitting the nondestructive observation of microbial
      interactions over space and time with single-cell resolution.

PMID- 29657966
TI  - Engineering Complexity in Bacterial Regulatory Circuits for Biotechnological
      Applications.
AB  - Engineering microbial systems allows the generation of new technologies having
      significant impact in the biotechnological industry and on human health. In the
      past few years, several synthetic biology approaches have been implemented in
      bacteria to allow precise engineering of novel regulatory circuits for several
      applications. The advent of high-throughput technologies and clustered regularly
      interspaced short palindromic repeat (CRISPR)/Cas9-based DNA editing techniques
      have been pivotal in this process. Yet, despite the tremendous advances
      experienced recently, there are still a number of bottlenecks that need to be
      overcome in order to generate high-performance redesigned living machines, and
      the use of novel computer-aided approaches would be essential for this task. In
      this perspective, we discuss some of the main advances in the field of microbial
      engineering and the new technologies and approaches that should allow the
      construction of on demand synthetic microbial factories through the redesign of
      regulatory complexity.

PMID- 29657967
TI  - At the Nexus of History, Ecology, and Hydrobiogeochemistry: Improved Predictions
      across Scales through Integration.
AB  - To improve predictions of ecosystem function in future environments, we need to
      integrate the ecological and environmental histories experienced by microbial
      communities with hydrobiogeochemistry across scales. A key issue is whether we
      can derive generalizable scaling relationships that describe this multiscale
      integration. There is a strong foundation for addressing these challenges. We
      have the ability to infer ecological history with null models and reveal impacts
      of environmental history through laboratory and field experimentation. Recent
      developments also provide opportunities to inform ecosystem models with targeted
      omics data. A major next step is coupling knowledge derived from such studies
      with multiscale modeling frameworks that are predictive under non-steady-state
      conditions. This is particularly true for systems spanning dynamic interfaces,
      which are often hot spots of hydrobiogeochemical function. We can advance
      predictive capabilities through a holistic perspective focused on the nexus of
      history, ecology, and hydrobiogeochemistry.

PMID- 29657968
TI  - Inferring the Minimal Genome of Mesoplasma florum by Comparative Genomics and
      Transposon Mutagenesis.
AB  - The creation and comparison of minimal genomes will help better define the most
      fundamental mechanisms supporting life. Mesoplasma florum is a near-minimal, fast
      growing, nonpathogenic bacterium potentially amenable to genome reduction
      efforts. In a comparative genomic study of 13 M. florum strains, including 11
      newly sequenced genomes, we have identified the core genome and open pangenome of
      this species. Our results show that all of the strains have approximately 80% of
      their gene content in common. Of the remaining 20%, 17% of the genes were found
      in multiple strains and 3% were unique to any given strain. On the basis of
      random transposon mutagenesis, we also estimated that ~290 out of 720 genes are
      essential for M. florum L1 in rich medium. We next evaluated different genome
      reduction scenarios for M. florum L1 by using gene conservation and essentiality
      data, as well as comparisons with the first working approximation of a minimal
      organism, Mycoplasma mycoides JCVI-syn3.0. Our results suggest that 409 of the
      473 M. mycoides JCVI-syn3.0 genes have orthologs in M. florum L1. Conversely, 57
      putatively essential M. florum L1 genes have no homolog in M. mycoides JCVI
      syn3.0. This suggests differences in minimal genome compositions, even for these
      evolutionarily closely related bacteria. IMPORTANCE The last years have witnessed
      the development of whole-genome cloning and transplantation methods and the
      complete synthesis of entire chromosomes. Recently, the first minimal cell,
      Mycoplasma mycoides JCVI-syn3.0, was created. Despite these milestone
      achievements, several questions remain to be answered. For example, is the
      composition of minimal genomes virtually identical in phylogenetically related
      species? On the basis of comparative genomics and transposon mutagenesis, we
      investigated this question by using an alternative model, Mesoplasma florum, that
      is also amenable to genome reduction efforts. Our results suggest that the
      creation of additional minimal genomes could help reveal different gene
      compositions and strategies that can support life, even within closely related
      species.

PMID- 29657969
TI  - Earth Microbiome Project and Global Systems Biology.

PMID- 29657970
TI  - Nonpareil 3: Fast Estimation of Metagenomic Coverage and Sequence Diversity.
AB  - Estimations of microbial community diversity based on metagenomic data sets are
      affected, often to an unknown degree, by biases derived from insufficient
      coverage and reference database-dependent estimations of diversity. For instance,
      the completeness of reference databases cannot be generally estimated since it
      depends on the extant diversity sampled to date, which, with the exception of a
      few habitats such as the human gut, remains severely undersampled. Further,
      estimation of the degree of coverage of a microbial community by a metagenomic
      data set is prohibitively time-consuming for large data sets, and coverage values
      may not be directly comparable between data sets obtained with different
      sequencing technologies. Here, we extend Nonpareil, a database-independent tool
      for the estimation of coverage in metagenomic data sets, to a high-performance
      computing implementation that scales up to hundreds of cores and includes, in
      addition, a k-mer-based estimation as sensitive as the original alignment-based
      version but about three hundred times as fast. Further, we propose a metric of
      sequence diversity (Nd ) derived directly from Nonpareil curves that correlates
      well with alpha diversity assessed by traditional metrics. We use this metric in
      different experiments demonstrating the correlation with the Shannon index
      estimated on 16S rRNA gene profiles and show that Nd additionally reveals
      seasonal patterns in marine samples that are not captured by the Shannon index
      and more precise rankings of the magnitude of diversity of microbial communities
      in different habitats. Therefore, the new version of Nonpareil, called Nonpareil
      3, advances the toolbox for metagenomic analyses of microbiomes. IMPORTANCE
      Estimation of the coverage provided by a metagenomic data set, i.e., what
      fraction of the microbial community was sampled by DNA sequencing, represents an
      essential first step of every culture-independent genomic study that aims to
      robustly assess the sequence diversity present in a sample. However, estimation
      of coverage remains elusive because of several technical limitations associated
      with high computational requirements and limiting statistical approaches to
      quantify diversity. Here we described Nonpareil 3, a new bioinformatics algorithm
      that circumvents several of these limitations and thus can facilitate culture
      independent studies in clinical or environmental settings, independent of the
      sequencing platform employed. In addition, we present a new metric of sequence
      diversity based on rarefied coverage and demonstrate its use in communities from
      diverse ecosystems.

PMID- 29657972
TI  - Evaluation of effect of bevacizumab on central subfield macular thickness in the
      injected and contralateral (untreated) eye of patients with bilateral diabetic
      macular oedema.
AB  - Purpose: Antivascular endothelial growth factor (anti-VEGFs)-bevacizumab is
      routinely utilised for the treatment of diabetic macular oedema (DME). We plan to
      evaluate the impact of bevacizumab on the central subfield macular thickness
      (CSMT) of the treated and untreated eye. Methods: A sequential group of patients
      with bilateral DME who were treated with unilateral bevacizumab injection were
      assessed preinjection and postinjection by Spectral Domain-Optical Coherence
      Tomography (SD-OCT) by CSMT. Results: Thirty-one patients, 20 male and 11 female,
      were evaluated. Seven patients had type 1 diabetes mellitus and 24 had type 2
      diabetes mellitus. In regard to the duration of disease, 23 patients had diabetes
      for more than 10 years, seven patients had the condition for 5-10 years and one
      patient for more than 5 years. Mean age of the patients was 60.48 years (SD+/
      7.13) with the range of 46-72 years. Mean follow-up was 28 days (range 26-35
      days). The eyes which received intravitreal injection had median CSMT of 473.2
      um(range 321-566 um). The CSMT of the contralateral eye had median of 347.6 um
      (range 357-437 um). A median reduction of -132 um (range 93-156 um) could be
      observed in the treated eye and -18 um (range 15-22) in the untreated eye after
      treatment. Our study also found that eyes with greater CSMT, when injected with
      bevacizumab, produced higher responses in the contralateral eye (R2 0.538,
      P<0.05). Conclusions: Patients with bilateral DME treated with bevacizumab in one
      eye produced a bilateral response. Eyes with greater CSMT due to DME elicited
      higher levels of response in the untreated eye.

PMID- 29657971
TI  - Genome Reduction in Psychromonas Species within the Gut of an Amphipod from the
      Ocean's Deepest Point.
AB  - Amphipods are the dominant scavenging metazoan species in the Mariana Trench, the
      deepest known point in Earth's oceans. Here the gut microbiota of the amphipod
      Hirondellea gigas collected from the Challenger and Sirena Deeps of the Mariana
      Trench were investigated. The 11 amphipod individuals included for analyses were
      dominated by Psychromonas, of which a nearly complete genome was successfully
      recovered (designated CDP1). Compared with previously reported free-living
      Psychromonas strains, CDP1 has a highly reduced genome. Genome alignment showed
      deletion of the trimethylamine N-oxide (TMAO) reducing gene cluster in CDP1,
      suggesting that the "piezolyte" function of TMAO is more important than its
      function in respiration, which may lead to TMAO accumulation. In terms of
      nutrient utilization, the bacterium retains its central carbohydrate metabolism
      but lacks most of the extended carbohydrate utilization pathways, suggesting the
      confinement of Psychromonas to the host gut and sequestration from more variable
      environmental conditions. Moreover, CDP1 contains a complete formate
      hydrogenlyase complex, which might be involved in energy production. The genomic
      analyses imply that CDP1 may have developed adaptive strategies for a lifestyle
      within the gut of the hadal amphipod H. gigas. IMPORTANCE As a unique but poorly
      investigated habitat within marine ecosystems, hadal trenches have received
      interest in recent years. This study explores the gut microbial composition and
      function in hadal amphipods, which are among the dominant carrion feeders in
      hadal habitats. Further analyses of a dominant strain revealed genomic features
      that may contribute to its adaptation to the amphipod gut environment. Our
      findings provide new insights into animal-associated bacteria in the hadal
      biosphere.

PMID- 29657974
TI  - Monocular and binocular visual impairment in the UK Biobank study: prevalence,
      associations and diagnoses.
AB  - Objective: To determine the prevalence of, associations with and diagnoses
      leading to mild visual impairment or worse (logMAR >0.3) in middle-aged adults in
      the UK Biobank study. Methods and analysis: Prevalence estimates for monocular
      and binocular visual impairment were determined for the UK Biobank participants
      with fundus photographs and spectral domain optical coherence tomography images.
      Associations with socioeconomic, biometric, lifestyle and medical variables were
      investigated for cases with visual impairment and matched controls, using
      multinomial logistic regression models. Self-reported eye history and image
      grading results were used to identify the primary diagnoses leading to visual
      impairment for a sample of 25% of cases. Results: For the 65 033 UK Biobank
      participants, aged 40-69 years and with fundus images, 6682 (10.3%) and 1677
      (2.6%) had mild visual impairment or worse in one or both eyes, respectively.
      Increasing deprivation, age and ethnicity were independently associated with both
      monocular and binocular visual impairment. No primary diagnosis for the recorded
      level of visual impairment could be identified for 49.8% of eyes. The most common
      identifiable diagnoses leading to visual impairment were cataract, amblyopia,
      uncorrected refractive error and vitreoretinal interface abnormalities.
      Conclusions: The prevalence of visual impairment in the UK Biobank study cohort
      is lower than for population-based studies from other industrialised countries.
      Monocular and binocular visual impairment are associated with increasing
      deprivation, age and ethnicity. The UK Biobank dataset does not allow confident
      identification of the causes of visual impairment, and the results may not be
      applicable to the wider UK population.

PMID- 29657975
TI  - Visual pathway function and structure in Wolfram syndrome: patient age, variation
      and progression.
AB  - Background/aims: To report alterations in visual acuity and visual pathway
      structure over an interval of 1-3 years in a cohort of children, adolescents and
      young adults who have Wolfram syndrome (WFS) and to describe the range of disease
      severity evident in patients with WFS whose ages differed by as much as 20 years
      at first examination. Methods: Annual, prospective ophthalmological examinations
      were performed in conjunction with retinal nerve fibre layer (RNFL) analysis.
      Diffusion tensor MRI-derived fractional anisotropy was used to assess the
      microstructural integrity of the optic radiations (OR FA). Results: Mean age of
      the 23 patients with WFS in the study was 13.8 years (range 5-25 years). Mean log
      minimum angle resolution visual acuity was 0.66 (20/91). RNFL thickness was
      subnormal in even the youngest patients with WFS. Average RNFL thickness in
      patients with WFS was 57+/-8 u or ~40% thinner than that measured in normal (94+/
      10 u) children and adolescents (P<0.01). Lower OR FA correlated with worse visual
      acuity (P=0.006). Subsequent examinations showed declines (P<0.05) in visual
      acuity, RNFL thickness and OR FA at follow-up intervals of 12-36 months. However,
      a wide range of disease severity was evident across ages: some of the youngest
      patients at their first examination had deficits more severe than the oldest
      patients. Conclusion: The genetic mutation of WFS causes damage to both
      pregeniculate and postgeniculate regions of the visual pathway. The damage is
      progressive. The decline in visual pathway structure is accompanied by declines
      of visual function. Disease severity differs widely in individual patients and
      cannot be predicted from their age.

PMID- 29657976
TI  - Efficacy of additional topical betamethasone in persistent cystoid macular oedema
      after carbonic anhydrase inhibitor treatments in retinitis pigmentosa.
AB  - Objective: We investigated the efficacy of additional topical betamethasone in
      persistent cystoid macular oedema (CMO) after carbonic anhydrase inhibitors
      (CAIs) therapy. Methods and analysis: This retrospective cohort study included 16
      eyes of 10 patients with retinitis pigmentosa (RP). All patients were previously
      administered CAI for at least 3 months to treat CMO secondary to RP and lacking
      an effective reduction (>=11%) of central foveal thickness (CFT). We administered
      topical 0.1% betamethasone daily in each affected eye following a preceding
      course of the CAI medication as a first treatment. CMO was diagnosed using
      spectral-domain optical coherence tomography. CFT was regarded as the average of
      vertical and horizontal foveal thickness. Best-corrected visual acuity (BCVA) and
      intraocular pressure (IOP) were obtained from patient medical records. We
      compared the CFT and BCVA between baseline and the average of 1-3, 5-7, 10-14 and
      16-20 months period. Results: In treatments with brinzolamide in 14 eyes,
      dorzolamide in 2 eyes and bromfenac in 2 eyes, CFT effectively decreased in 12 of
      16 eyes (81%). CFT decreased significantly in 1-3 months (326+/-102 um; n=16;
      P=0.029) and 5-7 months (297+/-102 um; n=12; P=0.022) compared with baseline but
      not within 10-14 months (271+/-96 um; n=9; P=0.485) or 16-20 months (281+/-134
      um; n=9; P=0.289). There were no significant intergroup differences in BCVA
      throughout the study. Betamethasone treatment was stopped in three patients
      because of IOP elevation. Conclusion: Our data suggested that additional
      betamethasone might improve treatments for persistent CMO. Topical steroids could
      be an alternative option for managing persistent CMO in RP.

PMID- 29657977
TI  - Expert practice patterns and opinions on corneal cross-linking for infectious
      keratitis.
AB  - Objective: To assess the current opinion and practice patterns from cornea
      experts regarding the benefit of corneal cross-linking (CXL) for infectious
      keratitis (IK). Methods and analysis: An international survey was distributed to
      corneal specialists via an internet survey. The survey data collected were
      analysed with descriptive statistics. Results: A survey was sent to 190
      recipients, and 29 (15%) respondents completed the survey with an average of 7
      years' experience using CXL. A majority of respondents (66%) used CXL to treat IK
      due to bacterial, fungal, protozoan or unknown aetiology. Main indications to use
      CXL as adjuvant therapy were worsening infiltrate diameter or depth despite
      therapy (74%), followed by antibiotic resistance (68%), corneal thinning (53%),
      poor compliance with medication (26%) and other reasons (21%). Most respondents
      felt CXL would be at least moderately helpful as an adjuvant therapy for
      bacterial (96%) or fungal (75%) keratitis; about half (46%) thought it would be
      helpful for acanthamoeba keratitis. As sole therapy, fewer respondents believed
      CXL would be at least moderately helpful to treat bacterial (75%), fungal (58%)
      and acanthamoeba (43%) keratitis. Conclusion: The survey offered insights into
      current expert practices and opinions of using CXL as therapy for IK. The results
      of this survey serve to guide in the design of future clinical studies.

PMID- 29657978
TI  - Relationship between electronically measured medication adherence and vision
      related quality of life in a cohort of patients with open-angle glaucoma.
AB  - Objective: To investigate whether electronically measured medication adherence is
      associated with vision-related quality of life (VRQoL) in patients with open
      angle glaucoma. Methods and analysis: This is a 3-year prospective cohort study
      of 79 subjects with open-angle glaucoma at a Veterans Affairs medical centre.
      Participants returned a medication event monitoring system (MEMS) for their
      glaucoma eye-drops and had at least two visits with glaucoma during the study
      period. Those taking less than 80% of prescribed glaucoma medication doses were
      considered to be non-adherent. Subjects were interviewed using the National Eye
      Institute's Visual Function Questionnaire-25 (VFQ-25) at baseline and after 3
      years. Results: Thirty per cent (n=24/79) of participants took less than 80% of
      prescribed doses of their glaucoma medications at baseline. Patients who did not
      adhere to their medications at baseline had lower mean composite VFQ-25 scores at
      baseline (70.66+/-20.50 vs 75.91+/-19.12, standardised mean difference=0.27) and
      after 3 years (71.68+/-21.93 vs 76.25+/-21.67, standardised mean
      difference=0.21). Visual acuity (P=0.03), but not visual field severity (P=0.13)
      or medication adherence (P=0.30), was significantly associated with composite VFQ
      25 score in an adjusted model. Conclusions: Subjects who were non-adherent to
      their glaucoma medications at baseline as assessed by a MEMS device reported
      lower VRQoL than adherent subjects at baseline and after 3 years. However, visual
      acuity was significantly associated with VRQoL. Future studies should assess
      whether improved adherence to eye-drops impacts VRQoL in patients with glaucoma.

PMID- 29657980
TI  - Clinical safety of a minor eye conditions scheme in England delivered by
      community optometrists.
AB  - Objective: The aim of this study was to monitor the activity and evaluate the
      clinical safety of a minor eye conditions scheme (MECS) conducted by accredited
      community optometrists in Lambeth and Lewisham, London. Methods and analysis:
      Optometrists underwent an accredited training programme, including attendance at
      hospital eye services (HES) clinics. Patients who satisfied certain inclusion
      criteria were referred to accredited MECS optometrists by their general
      practitioners (GPs) or could self-refer. Data were extracted from clinical
      records. A sample of MECS clinical records was graded to assess the quality of
      the MECS optometrists' clinical management decisions. Referrals to the HES were
      assessed by the collaborating ophthalmologists and feedback was provided.
      Results: A total of 2123 patients (mean age 47 years) were seen over 12 months.
      Two-thirds of the patients (67.3%) were referred by their GP. The most common
      reasons for patients needing a MECS assessment were 'red eye' (36.7% of
      patients), 'painful white eye' (11.1%), 'flashes and floaters' (10.2%); 8.7% of
      patients had a follow-up appointment. Of the patients seen, 75.1% were retained
      in the community, 5.7% were referred to their GP and 18.9% were referred to the
      HES. Of the HES referrals, 49.1% were routine, 22.6% urgent and 28.3% emergency.
      Of the records reviewed, 94.5% were rated as appropriately managed; 89.2% of the
      HES referrals were considered appropriate. Conclusion: The findings of this study
      indicate that optometrists are in a good position to work very safely within the
      remits of the scheme and to assess risk.

PMID- 29657979
TI  - Ready-made and custom-made eyeglasses in India: a cost-effectiveness analysis of
      a randomised controlled trial.
AB  - Objective: Ready-made spectacles have been suggested as a less resource-intensive
      treatment for the millions of people living with uncorrected refractive error
      (URE) in low-income environments. In spite of this interest, there have been no
      published economic evaluations examining the cost-effectiveness of ready-made
      spectacles. This study aims to determine the relative cost-effectiveness of
      offering ready-made spectacles (RMS) relative to no intervention as well as the
      relative cost-effectiveness of custom-made spectacles (CS) relative to RMS to
      treat URE. Methods and analysis: The relative cost-effectiveness of RMS relative
      to CS and no intervention was tested through a cost-effectiveness analysis from
      the health service provider perspective conducted alongside a double-masked
      randomised controlled trial in an urban hospital in Delhi, India. Participants
      were adults aged 18-45 years with >=1 dioptre (D) of URE. Results: There was no
      significant difference between the effectiveness of the CS and RMS interventions
      in improving visual acuity, but the CS was over four times the price of the RMS
      per patient (204 INR (US$2.42) and 792 INR (US$11.22)). The cost per unit
      improvement in logarithm of the minimum angle of resolution (logMAR) relative to
      baseline with the RMS intervention was 407 INR (US$4.35). Existing estimates of
      utility resulting from improvements in visual acuity result in incremental cost
      per quality-adjusted life years gained of between 212 INR and 1137 INR (US$0.44
      US$23.74) depending on the source of the utility estimate and assumed expected
      life of the spectacles. Conclusion: RMS represent a significantly cost-effective
      option for spectacle provision in low-resource settings. The RMS programme was
      substantially cheaper than an equivalent CS intervention while being effective in
      improving visual acuity for the majority of adults with refractive error in this
      setting. These findings provide further support for including RMS in programmes
      to address URE. Trial registration number: NCT00657670, Results.

PMID- 29657981
TI  - Acceptability and use of glaucoma virtual clinics in the UK: a national survey of
      clinical leads.
AB  - Objective: The purpose of this paper is to describe the findings of a national
      survey that aimed to estimate the proportion of Hospital Eye Service (HES) units
      using glaucoma virtual clinics, to determine how these services differ and to
      gauge clinicians' views and opinions on the safety and acceptability of this
      model of care compared with usual care. Methods and analysis: This 12-question
      survey was disseminated nationally to 92 clinical lead consultant
      ophthalmologists using SurveyMonkey. Results: The response rate was 45.7%. There
      were 21 out of the total 42 respondents (50.0%) who were based at an NHS Trust
      where glaucoma virtual clinics were already being used and a further 9 (21.4%)
      were planning to establish one. Clinical leads largely rated efficiency and
      patient safety to be at least equivalent to usual care (92.9%) and 81.0%
      perceived glaucoma virtual clinics to be acceptable to patients. The main reasons
      for not running glaucoma virtual clinics were insufficient staff (71.4%) and
      inadequate space (47.6%). The majority of those running virtual clinics used this
      model of care for 'lower risk' patients such as ocular hypertensives (90.5%) and
      glaucoma suspects. Conclusion: Glaucoma virtual clinics are employed by a large
      proportion of HES units, with many seeking to develop such services. Clinical
      leads largely rate efficiency, patient safety and the perception of patient
      acceptability to be at least equivalent to usual care.

PMID- 29657982
TI  - Epithelial ingrowth following laser in situ keratomileusis (LASIK): prevalence,
      risk factors, management and visual outcomes.
AB  - The number of laser in situ keratomileusis (LASIK) procedures is continuing to
      rise. Since its first application for correcting simple refractive errors over 25
      years ago, the role of LASIK has extended to treat other conditions, including
      postkeratoplasty astigmatism/ametropia, postcataract surgery refractive error and
      presbyopia, among others. The long-term effectiveness, predictability and safety
      have been well established by many large studies. However, due to the creation of
      a potential interface between the flap and the underlying stroma, interface
      complications such as infectious keratitis, diffuse lamellar keratitis and
      epithelial ingrowth may occur. Post-LASIK epithelial ingrowth (PLEI) is an
      uncommon complication that usually arises during the early postoperative period.
      The reported incidence of PLEI ranged from 0%-3.9% in primary treatment to 10%
      20% in retreatment cases. It can cause a wide spectrum of clinical presentations,
      ranging from asymptomatic interface changes to severe visual impairment and flap
      melt requiring keratoplasty. PLEI can usually be treated with mechanical
      debridement of the affected interface; however, additional interventions, such as
      alcohol, mitomycin C, fibrin glue, ocular hydrogel sealant,
      neodymium:yttriumaluminum garnet laser and amniotic membrane graft, may be
      required for recurrent or refractory cases. The aims of this review are to
      determine the prevalence and risk factors of PLEI; to describe its pathogenesis
      and clinical features and to summarise the therapeutic armamentarium and the
      visual outcome of PLEI.

PMID- 29657983
TI  - Discrete microfluidics for the isolation of circulating tumor cell subpopulations
      targeting fibroblast activation protein alpha and epithelial cell adhesion
      molecule.
AB  - Circulating tumor cells consist of phenotypically distinct subpopulations that
      originate from the tumor microenvironment. We report a circulating tumor cell
      dual selection assay that uses discrete microfluidics to select circulating tumor
      cell subpopulations from a single blood sample; circulating tumor cells
      expressing the established marker epithelial cell adhesion molecule and a new
      marker, fibroblast activation protein alpha, were evaluated. Both circulating
      tumor cell subpopulations were detected in metastatic ovarian, colorectal,
      prostate, breast, and pancreatic cancer patients and 90% of the isolated
      circulating tumor cells did not co-express both antigens. Clinical sensitivities
      of 100% showed substantial improvement compared to epithelial cell adhesion
      molecule selection alone. Owing to high purity (>80%) of the selected circulating
      tumor cells, molecular analysis of both circulating tumor cell subpopulations was
      carried out in bulk, including next generation sequencing, mutation analysis, and
      gene expression. Results suggested fibroblast activation protein alpha and
      epithelial cell adhesion molecule circulating tumor cells are distinct
      subpopulations and the use of these in concert can provide information needed to
      navigate through cancer disease management challenges.

PMID- 29657986
TI  - Clinical and Translational Radiation Oncology, a new player among the radiation
      oncology journals.

PMID- 29657984
TI  - B cell, CD8 + T cell and gamma delta T cell lymphocytic alveolitis alters
      alveolar immune cell homeostasis in HIV-infected Malawian adults.
AB  - Background: HIV infection is associated with increased risk to lower respiratory
      tract infections (LRTI). However, the impact of HIV infection on immune cell
      populations in the lung is not well defined. We sought to comprehensively
      characterise the impact of HIV infection on immune cell populations in the lung.
      Methods: Twenty HIV-uninfected controls and 17 HIV-1 infected ART-naive adults
      were recruited from Queen Elizabeth Central Hospital, Malawi. Immunophenotyping
      of lymphocyte and myeloid cell populations was done on bronchoalveolar lavage
      fluid and peripheral blood cells. Results: We found that the numbers of CD8 + T
      cells, B cells and gamma delta T cells were higher in BAL fluid of HIV-infected
      adults compared to HIV-uninfected controls (all p<0.05). In contrast, there was
      no difference in the numbers of alveolar CD4 + T cells in HIV-infected adults
      compared to HIV-uninfected controls (p=0.7065). Intermediate monocytes were the
      predominant monocyte subset in BAL fluid (HIV-, 63%; HIV+ 81%), while the numbers
      of classical monocytes was lower in HIV-infected individuals compared to HIV
      uninfected adults (p=0.0006). The proportions of alveolar macrophages and myeloid
      dendritic cells was lower in HIV-infected adults compared to HIV-uninfected
      controls (all p<0.05). Conclusions: Chronic HIV infection is associated with
      broad alteration of immune cell populations in the lung, but does not lead to
      massive depletion of alveolar CD4 + T cells. Disruption of alveolar immune cell
      homeostasis likely explains in part the susceptibility for LRTIs in HIV-infected
      adults.

PMID- 29657985
TI  - The Chlamydia muridarum plasmid revisited : new insights into growth kinetics.
AB  - Background: Research in chlamydial genetics is challenging because of its
      obligate intracellular developmental cycle. In vivo systems exist that allow
      studies of different aspects of basic biology of chlamydiae, the murine Chlamydia
      muridarum model is one of great importance and thus an essential research tool.
      C. muridarum carries a plasmid that has a role in virulence.  Our aim was to
      compare and contrast the C. muridarum plasmid-free phenotype with that of a
      chromosomally isogenic plasmid-bearing strain, through the inclusion phase of the
      developmental cycle. Methods: We measured infectivity for plasmid bearing and
      plasmid-cured C. muridarum by inclusion forming assays in McCoy cells and in
      parallel bacterial chromosome replication by quantitative PCR, throughout the
      developmental cycle. In addition to these studies, we have carefully monitored
      chlamydial inclusion formation by confocal microscopy and transmission electron
      microscopy. A new E.coli/chlamydial shuttle vector (pNigg::GFP) was constructed
      using standard cloning technology and used to transform C. muridarum for further
      phenotypic studies. Results: We have advanced the definition of the chlamydial
      phenotype away from the simple static observation of mature inclusions and
      redefined the C. muridarum plasmid-based phenotype on growth profile and
      inclusion morphology. Our observations on the growth properties of plasmid-cured
      C. muridarum challenge the established interpretations, especially with regard to
      inclusion growth kinetics. Introduction of the shuttle plasmid pNigg::GFP into
      plasmid-cured C. muridarum restored the wild-type plasmid-bearing phenotype and
      confirmed that loss of the plasmid was the sole cause for the changes in growth
      and chromosomal replication. Conclusions: Accurate growth curves and sampling at
      multiple time points throughout the developmental cycle is necessary to define
      plasmid phenotypes.  There are subtle but important (previously unnoticed)
      differences in the overall growth profile of plasmid-bearing and plasmid-free C.
      muridarum.  We have proven that the differences described are solely due to the
      plasmid pNigg.

PMID- 29657987
TI  - Automatic treatment planning improves the clinical quality of head and neck
      cancer treatment plans.
AB  - Background: Treatment plans for head and neck (H&N) cancer are highly complex due
      to multiple dose prescription levels and numerous organs at risk (OARs) close to
      the target. The plan quality is inter-planner dependent since it is dependent on
      the skills and experience of the dosimetrist. This study presents a blinded
      prospective clinical comparison of automatic (AU) and manually (MA) generated H&N
      VMAT plans made for clinical use. Methods: MA and AU plans were generated for 30
      consecutive patients in Pinnacle3 using the IMRT optimisation module and the new
      Autoplan module, respectively. The plan quality was blindedly compared by three
      senior oncologists and the best plan was selected for treatment of the patient.
      Planning time was measured as the active operator time used. The plan quality was
      analysed with DVH metrics and the dose delivery accuracy validated on the
      ArcCheck phantom. Results: For twenty-nine out of the thirty patients the AU plan
      was chosen for treatment. Target doses were more homogenous with the AU plans and
      the OAR doses were significantly reduced, between 0.5 and 6.5 Gy. The average
      operator time spent on creating a manual plan was 64 min which was halved by
      Autoplan. The AU plans were more modulated as illustrated by an increase in MUs,
      which might cause the slightly lower pass rate of 97.7% in the ArcCheck
      measurements. Conclusions: Target doses were similar between MA and AU plan,
      while AU plans spared all OAR considerably better than the MA plans.

PMID- 29657988
TI  - Outcomes for pediatric patients with central nervous system germ cell tumors
      treated with proton therapy.
AB  - Purpose: We assessed outcomes after proton therapy (PT) for central nervous
      system germinomas or non-germinomatous germ cell tumors (NGGCTs) in children.
      Patients and methods: We identified children with germ cell tumors of the central
      nervous system who received proton therapy in 2006-2009 and extracted information
      on tumor response, treatment failures, and toxicity. Results: Of the 20
      identified patients (median age 12 years [range 3-16]), 9 had germinoma and 11
      NGGCTs; 19 patients received three-dimensional conformal PT and 1 scanning-beam
      PT. Fourteen patients had craniospinal irradiation (CSI), 4 had ventricular
      irradiation that excluded the 4th ventricle, and 2 had whole-ventricle
      irradiation. All received involved-field boosts. At a median follow-up interval
      of 5.6 years (range, 0.3-8.2 years), 1 patient with germinoma had an out-of-field
      failure in the 4th ventricle and 2 with NGGCT died from disease progression after
      CSI. Rates of local control, progression-free survival, and overall survival at 5
      years were 89%, 89%, and 100% for patients with germinoma; corresponding rates
      for NGGCTs were 82%, 82%, and 82%. The most common late toxicity (9 patients
      [45%]) was endocrinopathy. Conclusions: PT for CNS germ cell tumors is associated
      with acceptable disease control rates and toxicity profiles.

PMID- 29657989
TI  - Perspectives on medical education in radiation oncology and the role of the ESTRO
      School.
AB  - Radiation oncology is a medical specialty not just delivering ionizing radiation
      to cancer patients but also participating as an important partner in the care of
      the patient from diagnosis to cure, follow up or end of life. The specialty is
      rapidly evolving in a multi- and interdisciplinary setting as multimodality
      treatment is becoming frequent. This requires that the medical undergraduate and
      postgraduate training evolve to these changes. The ESTRO School has for more than
      30 years offered postgraduate training courses in and outside Europe and strives
      to develop its services to accommodate the educational needs of a specialty in
      constant development. Some of these developments are described in the present
      paper.

PMID- 29657990
TI  - Independent validation of the prognostic value of cancer stem cell marker
      expression and hypoxia-induced gene expression for patients with locally advanced
      HNSCC after postoperative radiotherapy.
AB  - Objective: To validate the impact of HPV status, cancer stem cell (CSC) marker
      expression and tumour hypoxia status in patients with locally advanced head and
      neck squamous cell carcinoma (HNSCC), who received postoperative radiotherapy.
      The results of the exploration cohort have previously been reported by the German
      Cancer Consortium Radiation Oncology Group (DKTK-ROG; Lohaus et al., 2014; Linge
      et al., 2016). Materials and methods: For 152 patients with locally advanced
      HNSCC the impact of HPV16 DNA status, CSC marker expression and hypoxia
      associated gene signatures on outcome of postoperative radiotherapy were
      retrospectively analysed. Out of them, 40 patients received postoperative
      radiochemotherapy. Cox models presented in a previous study were validated using
      the concordance index as a performance measure. The primary endpoint of this
      study was loco-regional control. Results were compared to those previously
      reported by DKTK-ROG. Results: Loco-regional control, freedom from distant
      metastases and overall survival were inferior to the previously reported cohort.
      Despite of this, the prognostic value of the combination of HPV infection status,
      CSC marker expression (SLC3A2) and tumour hypoxia status could be validated in
      univariate analyses using an independent validation cohort. For multivariate
      models, the concordance index was between 0.58 and 0.69 in validation, indicating
      a good prognostic performance of the models. The inclusion of CD44 and the 15
      gene hypoxia signature moderately improved the performance compared to a baseline
      model without CSC markers or hypoxia classifiers. Conclusions: The HPV status,
      CSC marker expression of CD44 and SLC3A2 as well as hypoxia status are potential
      prognostic biomarkers for patients with locally advanced HNSCC treated by
      postoperative radiotherapy.

PMID- 29657991
TI  - Impact of waiting time on nodal staging in head and neck squamous-cell carcinoma
      treated with radical intensity modulated radiotherapy.
AB  - Background and purpose: To evaluate the influence of delays for radiotherapy on
      survival, recurrence and upstaging for head and neck squamous-cell carcinoma
      (HNSCC) with no nodal involvement treated with intensity modulated radiotherapy
      (IMRT). Material and methods: This retrospective study included 63 consecutive
      patients with HNSCC located in the pharynx and larynx and treated with exclusive
      IMRT with or without chemotherapy. Survival, loco-regional or distant failure and
      upstaging were analyzed according to the waiting time. Results: Mean waiting time
      for treatment was 62.5 days for the hypopharynx subgroup (range = 37-102), 63
      days for the larynx subgroup (range = 19-128) and 58.5 days for the oropharynx
      subgroup (range = 29-99) (p = 0.725). Nine patients (14%) experienced upstaging.
      Loco-regional or distant failure occurred in 18 patients. Beyond a delay of 50
      days, 19% of patients had local failure, 17% nodal recurrence and 11% distant
      failure. Within a delay of 50 days, no nodal or distant failure was observed and
      only 1 patient experienced local recurrence. Upstaging and overall survival were
      not significantly affected by an increased waiting time. Conclusion: For N0
      patients treated with IMRT for HNSCC, waiting time around 50 days after the
      diagnosis was not significantly associated with an excessive risk of upstaging or
      recurrence.

PMID- 29657992
TI  - Single nucleotide polymorphisms might influence chemotherapy induced nausea in
      women with breast cancer.
AB  - Background: Women receiving FEC (5 fluorouracil, epirubicin and cyclophosphamide)
      chemotherapy (CT) for breast cancer (BC) often experience side effects such as
      nausea and vomiting. Individual variations of side effects occur in patients
      despite similar cancer therapy. The purpose of this study was to investigate a
      possible genetic background as a predictor for individual variations in nausea
      induced by CT. Methods: 114 women were included in the study. All women received
      adjuvant CT for BC. Self-reported nausea and vomiting was recorded in a
      structured diary over ten days following treatment. Blood samples were collected
      before the treatment and used for the detection of 48 single nucleotide
      polymorphisms (SNPs) in 43 genes. SNPs from each individual woman were analyzed
      for their relation to the patient-reported frequency and intensity of nausea and
      vomiting. Results: Eighty-four percent (n = 96) of the women reported acute or
      delayed nausea or combined nausea and vomiting during the ten days following CT.
      Three out of the forty-eight SNPs in the following genes: FAS/CD95, RB1/LPAR6 and
      CCL2 were found to be associated with a risk of nausea. Conclusion: SNPs in the
      FAS/CD95, RB1/LPAR6 and CCL2 genes were found to be associated with nausea among
      women treated with adjuvant FEC for BC. SNPs analysis is fast and cost effective
      and can be done prior to any cancer therapy. The association between individual
      SNPs and severe side effects from FEC may contribute to a more personalized care
      of patients with BC.

PMID- 29657993
TI  - The HIV protease and PI3K/Akt inhibitor nelfinavir does not improve the curative
      effect of fractionated irradiation in PC-3 prostate cancer in vitro and in vivo.
AB  - Background: Radiotherapy has a high curative potential in localized prostate
      cancer, however, there are still patients with locally advanced tumours who face
      a considerable risk of recurrence. Radiosensitization using molecular targeted
      drugs could help to optimize treatment for this high-risk group. The PI3K/Akt
      pathway is overexpressed in many prostate cancers and is correlated to
      radioresistance. Nelfinavir, an HIV protease inhibitor (HPI), was found to block
      this pathway and to radiosensitize cancer cells of different origin. This is the
      first study examining the effect of nelfinavir in combination with irradiation on
      prostate cancer cell survival in vitro as well as on growth time and local tumour
      control in vivo. Methods: The in vitro effect of nelfinavir on radioresponse of
      PC-3 was tested by colony formation assay with 10 MUM nelfinavir. In vivo, the
      effect of nelfinavir alone and in combination with irradiation was tested in nude
      mice carrying PC-3 xenografts. For evaluating tumour growth time, mice were
      treated with 80 mg nelfinavir/kg body weight, daily at 5 days per week over 6
      weeks. Simultaneous irradiation with 30 fractions and total doses between 30 and
      120 Gy was applied to calculate local tumour control for day 180 after treatment.
      Results: Nelfinavir inhibited Akt phosphorylation at Ser473 and showed a minor
      but significant effect on clonogenic cell survival in vitro with slightly higher
      cell survival rates after combined treatment. The treatment of PC-3 xenografts
      with nelfinavir alone led to no significant increase of tumour growth time and no
      improvement of local tumour control. Conclusions: Despite promising growth delay
      effects of nelfinavir in other tumour models and first clinical applications of
      this drug as anti-cancer agent, PC-3 prostate cancer cells express no or only
      minor sensitivity to nelfinavir treatment alone and no radiosensitizing effect in
      vitro or in vivo.

PMID- 29657994
TI  - Study of diffusion weighted MRI as a predictive biomarker of response during
      radiotherapy for high and intermediate risk squamous cell cancer of the
      oropharynx: The MeRInO study.
AB  - Introduction and background: A significant proportion of patients with
      intermediate and high risk squamous cell cancer of the oropharynx (OPSCC)
      continue to relapse locally despite radical chemoradiotherapy (CRT). The toxicity
      of the current combination of intensified dose per fraction radiotherapy and
      platinum based chemotherapy limits further uniform intensification. If a
      predictive biomarker for outcomes from CRT can be identified during treatment
      then individualised and adaptive treatment strategies may be employed.
      Methods/design: The MeRInO study is a prospective observational imaging study of
      patients with intermediate and high risk, locally advanced OPSCC receiving
      radical RT or concurrent CRT Patients undergo diffusion weighted MRI prior to
      treatment (MRI_1) and during the third week of RT (MRI_2). Apparent diffusion
      coefficient (ADC) measurements will be made on each scan for previously specified
      target lesions (primary and lymph nodes) and change in ADC calculated. Patients
      will be followed up and disease status for each target lesion noted. The primary
      aim of the MeRInO study is to determine the threshold change in ADC from baseline
      to week 3 of RT that may identify the sub-group of non-responders during
      treatment. Discussion: The use of DW-MRI as a predictive biomarker during RT for
      SCC H&N is in its infancy but studies to date have found that response to
      treatment may indeed be predicted by comparison of DW-MRI carried out before and
      during treatment. However, previous studies have included all sub-sites and
      biological sub-types. Establishing ADC thresholds that predict for local failure
      is an essential step towards using DW-MRI to improve the therapeutic ratio in
      treating SCC H&N. This would be done most robustly in a specific H&N sub-site and
      in sub-types with similar biological behaviour. The MeRInO study will help
      establish these thresholds in OPSCC.

PMID- 29657995
TI  - First reported treatment of aggressive hemangioma with intraoperative radiation
      therapy and kyphoplasty (Kypho-IORT).
AB  - Aggressive hemangiomas invade the spinal canal and/or paravertebral space and may
      cause cord compression and neurological symptoms. Radiation therapy was
      recognized as an effective strategy for the treatment of aggressive hemangiomas.
      Here, it is reported the first case of aggressive vertebral hemangioma treated by
      a combination of intraoperative radiation therapy and kyphoplasty (Kypho-IORT).

PMID- 29657996
TI  - Significant tumor shift in patients treated with stereotactic radiosurgery for
      brain metastasis.
AB  - Introduction: Linac-based stereotactic radiosurgery (SRS) for brain metastases
      may be influenced by the time interval between treatment preparation and
      delivery, related to risk of anatomical changes. We studied tumor position shifts
      and its relations to peritumoral volume edema changes over time, as seen on MRI.
      Methods: Twenty-six patients who underwent SRS for brain metastases in our
      institution were included. We evaluated the occurrence of a tumor shift between
      the diagnostic MRI and radiotherapy planning MRI. For 42 brain metastases the
      tumor and peritumoral edema were delineated on the contrast enhanced T1weighted
      and FLAIR images of both the diagnostic MRI and planning MRI examinations. Centre
      of Mass (CoM) shifts and tumor borders were evaluated. We evaluated the influence
      of steroids on peritumoral edema and tumor volume and the correlation with CoM
      and tumor border changes. Results: The median values of the CoM shifts and of the
      maximum distances between the tumor borders obtained from the diagnostic MRI and
      radiotherapy planning MRI were 1.3 mm (maximum shift of 5.0 mm) and 1.9 mm
      (maximum distance of 7.4 mm), respectively. We found significant correlations
      between the absolute change in edema volume and the tumor shift of the CoM (p <
      0.001) and tumor border (p = 0.040). Patients who received steroids did not only
      had a decrease in peritumoral edema, but also had a median decrease in tumor
      volume of 0.02 cc while patients who did not receive steroids had a median
      increase of 0.06 cc in tumor volume (p = 0.035). Conclusion: Our results show
      that large tumor shifts of brain metastases can occur over time. Because shifts
      may have a significant impact on the local dose coverage, we recommend minimizing
      the time between treatment preparation and delivery for Linac based SRS.

PMID- 29657998
TI  - Dosimetric assessment of an Atlas based automated segmentation for loco-regional
      radiation therapy of early breast cancer in the Skagen Trial 1: A multi
      institutional study.
AB  - The effect of Atlas-based automated segmentation (ABAS) on dose volume histogram
      (DVH) parameters compared to manual segmentation (MS) in loco-regional
      radiotherapy (RT) of early breast cancer was investigated in patients included in
      the Skagen Trial 1. This analysis supports implementation of ABAS in clinical
      practice and multi-institutional trials.

PMID- 29657999
TI  - Sequential histological findings and clinical response after carbon ion
      radiotherapy for unresectable sarcoma.
AB  - Background and purpose: The efficacy of carbon ion radiotherapy (CIRT) for bone
      and soft tissue sarcoma has been reported recently. Although histological
      assessment after CIRT requires skilled interpretation, little information is
      presently available. In this study, we report sequential histological findings
      after treatment with CIRT, and evaluate the association between these findings
      and clinical response. Material and methods: Seven patients with unresectable
      sarcoma underwent needle biopsy 12 times at an average of 14.3 months after CIRT
      and were included in this study. Results: One patient underwent two biopsies
      after CIRT for chordoma. Although a few suspected residual chordoma cells were
      observed at 19 and 30 months after CIRT, the tumor continued to shrink at 75
      months. Immunohistochemical analysis of post-CIRT specimens revealed CK AE1/3,
      EMA, and S100 expression, as in the pre-CIRT specimen. In total, viable tumor
      cells were found in 9 of 12 specimens; however, only 2 patients showed recurrent
      masses on radiological examination. The other 5 patients had stable disease.
      Conclusions: Viable tumor cells after CIRT did not always cause recurrence. This
      may be due to observation of dying cells or radiation-induced deformed cells.
      Histological evaluation after CIRT should be done carefully.

PMID- 29657997
TI  - Beyond checkpoint inhibition - Immunotherapeutical strategies in combination with
      radiation.
AB  - The revival of cancer immunotherapy has taken place with the clinical success of
      immune checkpoint inhibition. However, the spectrum of immunotherapeutic
      approaches is much broader encompassing T cell engaging strategies, tumour
      specific vaccination, antibodies or immunocytokines. This review focuses on the
      immunological effects of irradiation and the evidence available on combination
      strategies with immunotherapy. The available data suggest great potential of
      combined treatments, yet also poses questions about dose, fractionation, timing
      and most promising multimodal strategies.

PMID- 29658000
TI  - Plasma proteins as prognostic biomarkers in radiotherapy treated head and neck
      cancer patients.
AB  - Background: Blood-based protein biomarkers can be a useful tool as pre-treatment
      prognostic markers, as they can reflect both variations in the tumor
      microenvironment and the host immune response. We investigated the influence of a
      panel of plasma proteins for the development of any failure defined as recurrent
      disease in the T-, N-, or M-site in HNSCC. Methods: We used a multiplex bead
      based approach to analyze 19 proteins in 86 HNSCC patients and 15 healthy
      controls. We evaluated the associations between the biomarkers, loco-regional
      failure, failure in the T-, N-, or M-site, overall survival (OS), p16 status, and
      hypoxia. Results: In 41 p16 positive oropharynx cancer patients we identified a
      profile of biomarkers consisting of upregulation of IL-2, IL-4, IL-6, IL-8,
      eotaxin, GRO-a, and VEGF and downregulation of VEGFR-1 and VEGFR-2 with a
      significantly reduced risk of failure (p < 0.01). None of the individual proteins
      were associated with outcome. Conclusion: The identified plasma profile
      potentially reflects an activated immune response in a subgroup of the p16
      positive patients.

PMID- 29658001
TI  - Glut-1 expression in small cervical biopsies is prognostic in cervical cancers
      treated with chemoradiation.
AB  - Background/purpose: Chemoradiation (CRT) is standard therapy for locally advanced
      cervical cancer (LACC). However, there is a lack of biomarkers to identify
      patients at high relapse-risk. We examine metabolic (glucose transporter-1 [Glut
      1]), hypoxic (hypoxia inducible factor [HIF-1alpha]; carbonic anhydrase [CA-9])
      and proliferative (Ki-67) markers for prognostic utility in LACC.
      Materials/methods: 60 LACC patients treated with CRT had pre-treatment biopsies.
      Immunohistochemistry was performed for Glut-1, HIF-1a and CA-9, to generate a
      histoscore from intensity and percentage staining; and Ki-67 scored by percentage
      of positive cells. For each biomarker, treatment response and survival was
      compared between low and high-staining groups by logrank testing and multivariate
      analyses. Results: High Glut-1 expression was associated with inferior
      progression-free survival (PFS), (hazard ratio [HR] 2.8, p = 0.049) and overall
      survival (OS), (HR 5.0, p = 0.011) on multifactor analysis adjusting for stage,
      node positivity, tumour volume and uterine corpus invasion. High Glut-1
      correlated with increased risk of distant failure (HR 14.6, p = 0.001) but not
      local failure. Low Glut-1 was associated with higher complete metabolic response
      rate on post-therapy positron emission tomography scan (odds ratio 3.4, p =
      0.048). Ki-67 was significantly associated with PFS only (HR 1.19 per 10 units
      increase, p = 0.033). Biomarkers for hypoxia were not associated with outcome.
      Conclusions: High Glut-1 in LACC is associated with poor outcome post CRT. If
      prospectively validated, Glut-1 may help select patients for more intensive
      treatment regimens.

PMID- 29658002
TI  - Simultaneous integrated prophylactic cranial irradiation in sino-nasal cancer.
AB  - Therapy for small cell cancer and high grade neuroendocrine tumours of the
      paranasal sinuses is extrapolated from the treatment of small cell lung cancer
      and paranasal cancer of different histologies. Prophylactic cranial irradiation
      has proven survival benefit in small cell lung cancer. Two patients with
      aggressive cancer of the paranasal sinuses received radiotherapy with
      simultaneous integrated prophylactic brain irradiation, using two sequential
      plans. Chemotherapy was given before, during and after radiotherapy. None of the
      patients had intracranial recurrence. One patient experienced severe, but
      transient encephalitis-like symptoms that could only be attributed to
      radiotherapy. No long term side effects in the CNS were observed. The treatment
      was feasible, but with possible severe, but transient side effects. It should be
      considered in cases with head and neck cancer, with a high risk of intracerebral
      metastasis, as well as a significant overlap between the primary irradiated
      volume and the brain.

PMID- 29658003
TI  - Profiling of a panel of radioresistant prostate cancer cells identifies
      deregulation of key miRNAs.
AB  - Background: miRNAs are increasingly associated with the aggressive phenotype of
      prostate tumours. Their ability to control radiobiologically-relevant cellular
      processes strengthens their potential as novel markers of response to radiation
      therapy. Purpose: To identify miRNAs associated with increased clonogenic
      survival following radiation exposure. Material and methods: The miRNA expression
      profiles of a panel of 22RV1 cells with varying levels of radiosensitivities
      (hypoxic H-22Rv1 cells, RR-22Rv1 cells derived from WT-22Rv1 cells through 2-Gy
      fractionated repeated exposure, the associated aged matched cells (AMC-22Rv1) and
      the WT-22Rv1 cell lines) were generated and cross-analysed to identify common
      miRNAs associated with a radioresistant phenotype. Results: Increased clonogenic
      survival following irradiation was associated with significant modifications in
      miRNA expression pattern. miR-221 (up) and miR-4284 (down) in RR-22Rv1 and MiR-31
      and miR-200c in AMC-22Rv1 were the most uniquely significantly deregulated miRNAs
      when compared to WT-22Rv1 cells. miR-200c ranked as the most downregulated miRNAs
      in hypoxic, when compared to RR-22Rv1 cells. miR-200a was the only differentially
      expressed miRNA between RR-22Rv1 and AMC-22Rv1 cells. miR-210 yielded the highest
      fold change in expression in H-22Rv1, when compared to WT-22RV1 cells.
      Conclusion: This study identifies candidate miRNAs for the development of novel
      prognostic biomarkers for radiotherapy prostate cancer patients.

PMID- 29658004
TI  - In cancer cell lines inhibition of SCF/c-Kit pathway leads to radiosensitization
      only when SCF is strongly over-expressed.
AB  - Background and purpose: The SCF/c-Kit pathway is often overexpressed in human
      tumors leading to an enhanced tumorigenesis, proliferation and migration. It was
      now tested for NSCLC and prostate cancer cells growing in 2D and 3D whether the
      inhibition of this pathway can be used to achieve a significant
      radiosensitization and whether a respective biomarker may be identified. Material
      and methods: Experiments were performed with different cancer cell lines (NSCLC:
      H23, H520, H226, H1975 and PrCa: DU145) growing either under 2D or 3D conditions.
      Expression of SCF and c-Kit was determined by RT-PCR and Western blot, SCF was
      knocked down by siRNA, c-Kit was inhibited by ISCK03 inhibitor and cell survival
      was determined by colony formation assay. Results: There is a profound variation
      in the expression of both c-Kit and SCF with no association between each other.
      Neither levels did correlate with the respective cellular radiosensitivity
      determined for 2D or 3D with only a trend seen for SCF. Knock-down of SCF was
      generally found to result in no or only minor reduction of plating efficiency or
      cellular radioresistance. A significant reduction was only obtained for H520
      cells characterized by an extreme over-expression of SCF. The inhibition of c-Kit
      by a specific inhibitor was also found to result only in minor
      radiosensitization. Conclusion: Generally, the SCF/c-Kit pathway does not have a
      dominant effect on both, cell survival and radioresponse and, as a consequence,
      knockdown of this pathway does not result in a strong effect on radioresistance,
      except when SCF is strongly over-expressed.

PMID- 29658005
TI  - Follow up results of a prospective study to evaluate the impact of FDG-PET on CT
      based radiotherapy treatment planning for oesophageal cancer.
AB  - Background: This prospective study aims to determine the impact of PET/CT on
      radiotherapy planning and outcomes in patients with oesophageal cancer. Methods:
      All patients underwent PET/CT scanning in the radiotherapy treatment position,
      and received treatment planned using the PET/CT dataset. GTV was defined
      separately on PET/CT (GTV-PET) and CT (GTV-CT) datasets. A corresponding PTV was
      generated for each patient. Volumetric and spatial analysis quantified the
      proportion of FDG-avid disease not included in CT-based volumes. Clinical data
      was collected to determine locoregional control and overall survival rates.
      Results: 13 (24.1%) of 57 accrued patients had metastatic disease detected on
      PET. Median follow up was 4 years. FDG-avid disease would have been excluded from
      GTV-CT in 29 of 38 patients (76%). In 5 patients, FDG-avid disease would have
      been completely excluded from the PTV-CT. GTV-CT underestimated the cranial and
      caudal extent of FDG-avid tumour in 14 (36%) and 10 (26%) patients. 4-Year
      overall survival and locoregional failure free survival were 37% and 65%.
      Conclusions: PET/CT altered the delineation of tumour volumes when compared to CT
      alone, and should be considered standard for treatment planning. Although
      clinical outcomes were not improved with PET/CT planning, it did allow the use of
      smaller radiotherapy volumes.

PMID- 29658006
TI  - The clinical target volume in lung, head-and-neck, and esophageal cancer: Lessons
      from pathological measurement and recurrence analysis.
AB  - Radiotherapy research has achieved remarkable progress in target volume
      definition. Advances in medical imaging facilitate more precise localization of
      the gross tumor volume, alongside a more detailed understanding of the geometric
      uncertainties associated with treatment delivery that has enabled robust safety
      margins to be customized to the specific treatment scenario at hand. By contrast,
      the clinical target volume, meant to encompass gross tumor, as well as, adjacent
      sub-clinical disease, has evolved very little. It is more often defined by
      clinician experience and institutional convention than on a patient-specific
      basis. This disparity arises from the inherent invisibility of sub-clinical
      disease in current medical imaging. Its incidence and expanse can only be
      ascertained via indirect means. This article reviews two such strategies:
      histopathological measurements on resection specimen and analyses of locoregional
      recurrences after radiotherapy.

PMID- 29658007
TI  - Organ preservation in rectal cancer - Challenges and future strategies.
AB  - Neoadjuvant radiochemotherapy with subsequent total mesorectal excision is the
      standard of care for locally advanced rectal cancer. While this multimodal
      strategy has decreased local recurrences rates below 5%, long-term morbidities
      are considerable in terms of urinary, sexual or bowel functioning. At the same
      time approximately 10-20% of patients have no evidence of residual tumour in
      their surgical specimen. Pioneering studies from Brazil have suggested that
      surgery can safely be omitted in carefully selected patients with a clinical
      complete response after radiochemotherapy. Although confirmatory studies showed
      similar results, challenges in terms of optimizing radiochemotherapy for organ
      preservation, appropriate selection of patients for non-operative management and
      the safety of this approach remain. The present review will summarize the current
      data on organ-preservation in rectal cancer and discuss the challenges that need
      to be addressed in future trials.

PMID- 29658008
TI  - The role of Next-Generation Sequencing in tumoral radiosensitivity prediction.
AB  - Technological advances have led to more precise radiation delivery, which has
      resulted in significant clinical gains. A better understanding of tumoral
      radiosensitivity is still needed to develop strategies and further personalize
      radiation treatments. Next-Generation Sequencing (NGS) and system biology have
      significantly transformed the field of oncology in the last two decades, but have
      only a few clinical applications in radiation oncology. This review describes the
      technical aspects and evolutions of NGS and discusses the latest clinical
      applications of genomics to predict tumoral radiosensitivity.

PMID- 29658009
TI  - Biomarkers for nonclinical infusion reactions in marketed biotherapeutics and
      considerations for study design.
AB  - The observation of an infusion reaction (IR) in a nonclinical study can cause
      concern among investigators and regulators in the development of biotherapeutics.
      Biomarkers can be informative to determine whether the reactions are immune
      mediated or test-article related and if there is a potential risk to human
      subjects. IRs encompass a broad range of adverse events with a variety of
      triggers; the focus of this paper is IRs due to cytokine release syndrome or
      immune complex formation and the associated biomarkers. Such reactions generally
      do not preclude clinical development or marketing approval, because it is widely
      accepted that immune-mediated reactions in nonclinical species are not predictive
      of human outcomes. Several US approved products (from 2004 to 2016) have
      documented IRs in nonclinical species. This review article discusses recent
      examples, the biomarkers evaluated, and implications for study design and
      conduct.

PMID- 29658010
TI  - Impact of Intrinsic Structural Properties on the Hydration of 2:1 Layer
      Silicates.
AB  - Several 2:1 layer silicates comprising di- and trioctahedral smectites of
      different layer charge between 0.2 and 0.4 per formula unit and a trioctahedral
      vermiculite were studied by an in situ method that allowed Fourier transform
      infrared spectroscopy (FTIR) spectra and water vapor sorption isotherms to be
      obtained simultaneously. The particle size and shape of the selected materials
      were determined using X-ray diffraction and gas adsorption analyses, which
      provided an estimate of the particle size with resulting edge site proportion.
      The aim of this study was to elucidate the hydration mechanism in 2:1 layer
      silicates during desorption and adsorption of water vapor. Domains in the
      desorption and adsorption of water vapor of the smectite samples with a slightly
      increasing slope were explained by a heterogeneous layer charge distribution,
      which enables the coexistence of different hydration states even under controlled
      conditions. Whereas hysteresis was observed over the entire isothermal range of
      the smectites, the isotherm of the vermiculite sample only showed hysteresis in
      the transition from the monohydrated state (1W) to the bihydrated state (2W). We
      also revealed that hysteresis is a function of the layer charge distribution, the
      achieved water content, and the particle size with resulting edge site
      contribution. Increasing the edge site proportions led to an increased
      hysteresis. The findings from the experimental FTIR/gravimetric analysis showed
      that the transition from 2W to 1W and backward is visible using infrared
      spectroscopy. The shifting of delta(H-O-H) was influenced by the layer charge and
      octahedral substitutions. As a final point, we use water as a sensor molecule to
      describe the OH groups of the octahedral sheet and show that the observed shifts
      result from a change in the tilting angle. Our experimental results were
      supported by ab initio thermodynamic simulations that revealed the different
      shifting behavior of delta(H-O-H) and delta(M x+-OH-N y+) related to the
      differences in surface charge density and octahedral compositions.

PMID- 29658011
TI  - A Listeria-derived polypeptide promotes in vivo activation of NK cells for
      antitumor therapy.
AB  - Immunotherapies have shown promise in treatment of cancer, but more potent and
      targeted therapies are needed. Natural killer (NK) cells are lymphocytes with
      innate ability to recognize and lyse tumor cells. When activated, they also
      produce type II interferon (IFNgamma) to orchestrate the activity of other immune
      cells. Strategies to elicit NK cell activation in vivo have potential usefulness
      in anti-tumor immunotherapies. Here, we report on a strategy to stimulate NK cell
      activation and anti-tumor activity in mice with established B16.F10 murine
      melanomas. We and others previously observed that NK cells are rapidly activated
      during infection by pathogens such as the bacterium Listeria monocytogenes (Lm).
      A secreted Lm virulence protein, p60, and a fragment of p60 termed L1S were
      previously shown to stimulate innate immune responses and promote NK cell
      activation. We purified recombinant L1S and characterized its activity in cell
      culture studies. Recombinant L1S protein was also observed to promote
      accumulation and robust NK cell activation in the lungs when given via
      intratracheal instillation to control and tumor-bearing mice. Importantly,
      therapeutic administration of a single L1S dose was found to significantly reduce
      the number and area of "metastatic" tumor nodules on the lungs of mice with
      established B16.F10 murine melanomas. Depletion studies showed that these
      antitumor effects were dependent on NK cells and IFNgamma. These data provide
      proof of concept that administration of a single immune-modulating microbial
      polypeptide can be used to therapeutically boost NK cell in vivo activation and
      promote anti-tumor responses.

PMID- 29658012
TI  - Enzymatic Responses to Alcohol and Tobacco Nicotine-Derived Nitrosamine Ketone
      Exposures in Long Evans Rat Livers.
AB  - Background: Chronic feeding plus binge administration of ethanol causes very high
      blood alcohol concentrations. However, its co-administration with tobacco
      Nicotine-Derived Nitrosamine Ketone (NNK) results in somewhat lower blood alcohol
      levels, suggesting that NNK and therefore smoking, alters alcohol metabolism in
      the liver. To explore this hypothesis, we examined effects of ethanol and/or NNK
      exposures on the expression and activity levels of enzymes that regulate their
      metabolism in liver. Methods: This study utilized a 4-way model in which Long
      Evans rats were fed liquid diets containing 0% or 26% ethanol for 8 weeks, and
      respectively i.p injected with saline or 2 g/kg of ethanol 3 times/week during
      Weeks 7 and 8. The control and ethanol-exposed groups were each sub-divided and
      further i.p treated with 2 mg/kg of NNK or saline (3*/week) in Weeks 3-8. ADH,
      catalase and ALDH activities were measured using commercial kits. CYP450 mRNA
      levels (17 isoforms) were measured by qRT-PCR analysis. Results: Ethanol
      significantly increased hepatic ADH but not catalase or ALDH activity. NNK had no
      effect on ADH, ALDH, or catalase, but when combined with ethanol, it increased
      ADH activity above the levels measured in all other groups. Ethanol increased
      CYP2C7, while NNK increased CYP2B1 and CYP4A1mRNA levels relative to control. In
      contrast, dual ethanol + NNK exposures inhibited CYP2B1 and CYP4A1 expression
      relative to NNK. Conclusion: Dual exposures to ethanol and NNK increase hepatic
      ethanol metabolism, and ethanol and/or NNK exposures alter the expression of
      CYP450 isoforms that are utilized in NNK and fatty acid metabolism.

PMID- 29658013
TI  - Method for the Culture of Mouse Pulmonary Microvascular Endothelial Cells.
AB  - Pulmonary microvascular endothelial cells (ECs) are integral to the alveoli
      capillary barrier of the lung. The EC barrier integrity is known to be disrupted
      in severe lung diseases such as acute respiratory distress syndrome (ARDS),
      pneumonia and pulmonary edema. Mice are commonly used to model these diseases,
      dictating an increasingly high demand for murine ECs isolation and culture.
      Despite the significant number of protocols for the culture of various types of
      murine cells, the isolation of microvascular endothelial cells remains a
      challenging procedure. In our manuscript we developed adetailed step-by-step
      refined method for isolation murine pulmonary microvascular ECs for in vitro
      studies. We separated cells using platelet endothelial cell adhesion molecule
      antibody and characterized ECs with antibodies against intercellular adhesion
      molecule-1, acetylated-low density lipoprotein, and vascular endothelial (VE)
      cadherin. Further, we confirmed microvascular origin of these cells using
      Griffonia simplicifolia and Helix pomatia (negative control) staining. Barrier
      properties of EC monolayer were characterized by conducting electric cell
      substrate impedance sensing experiments with the edemagenic agents,
      lipopolysaccharide and nocodazole, and known barrier-protective agents, adenosine
      and sphingosine-1-phosphate. The described complete protocol provided consistent
      and reproducible results.

PMID- 29658014
TI  - Isomeric organic semiconductors containing fused-thiophene cores: molecular
      packing and charge transport.
AB  - Isomeric TF1 and TF2 with highly fused thiophene cores were designed and
      synthesized here, in which a highly planar molecular structure was obtained for
      TF1 with the face-to-face sulfur atoms in the lateral region and a twisted
      molecular backbone was observed for TF2 with the back-to-back sulfur atoms. It is
      worth noting that different intermolecular interactions dominated in TF1 and TF2
      caused by their isomeric thiophene cores, in which strong pi-pi stacking was
      achieved for TF1, whereas sulphur-involved nonbonding intermolecular interactions
      dominated in TF2, leading to the different fluorescence behaviors and also the
      altered liquid crystalline phases. Finally, typical P-type charge transport
      behaviors were achieved in both TF1- and TF2-based solution-processed OFETs. Also
      owing to the much ordered molecular packing in TF1, a higher charge carrier
      mobility of 3.7 * 10-3 cm2 V-1 s-1 was achieved for TF1-based OFETs compared to
      TF2-based OFETs.

PMID- 29658015
TI  - Stretchable V2O5/PEDOT supercapacitors: a modular fabrication process and
      charging with triboelectric nanogenerators.
AB  - Stretchable energy storage devices are of great importance for the viable
      applications of wearable/stretchable electronics. Studies on stretchable energy
      storage devices, especially supercapacitors (SCs), have shown encouraging
      progress. However, challenges still remain in the pursuit of high specific
      capacitances and facile fabrication methods. Herein, we report a modular
      materials fabrication and assembly process for stretchable SCs. With a V2O5/PEDOT
      composite as the active material, the resulting stretchable SCs exhibited high
      areal specific capacitances up to 240 mF cm-2 and good capacitance retention at a
      strain of 50%. To demonstrate the facile assembly process, a stretchable
      wristband was fabricated by simply assembling SC cells in series to deliver a
      voltage higher than 2 V. Charging the wristband with a triboelectric
      nanogenerator (TENG) to light an LED was further demonstrated, indicating the
      potential to integrate our SCs with environmental energy harvesters for self
      powered stretchable devices.

PMID- 29658016
TI  - Self-assembly study of nanometric spheres from polyoxometalate-phenylalanine
      hybrids, an experimental and theoretical approach.
AB  - Herein, we report on the study of supramolecular assemblies based on
      polyoxometalates (POMs) upon their modification with amino acids. Two POM-amino
      acid hybrids were synthesized by coupling a functionalized Keggin type
      polyoxoanion [PW11O39{Sn(C6H4)C[triple bond, length as m-dash]C(C6H4)COOH}]4-
      with carboxyl-protected (methyl-ester) phenylalanine or diphenylalanine peptides.
      Surprisingly, all compounds, including the initial POM, formed supramolecular
      nanospheres in different solvent mixtures, which were examined by scanning
      electron microscopy (SEM). Molecular dynamics (MD) simulations for the POM-amino
      acid species revealed that the hydrophobic forces are mainly responsible for the
      initial aggregation into incipient micelle type structures, in which the organic
      arms are buried inside the aggregate while POM polar heads are more exposed to
      the solvent with tetrabutyl-ammonium counter cations acting as linkers.

PMID- 29658017
TI  - Vertically-aligned Co3O4 arrays on Ni foam as monolithic structured catalysts for
      CO oxidation: effects of morphological transformation.
AB  - A generic hydrothermal synthesis route has been successfully designed and
      utilized to in situ grow highly ordered Co3O4 nanoarray (NA) precursors on Ni
      substrates, forming a series of Co3O4 nanoarray-based monolithic catalysts with
      subsequent calcination. The morphology evolution of Co3O4 nanostructures which
      depends upon the reaction time, with and without CTAB or NH4F is investigated in
      detail, which is used to further demonstrate the growth mechanism of Co3O4
      nanoarrays with different morphologies. CO is chosen as a probe molecule to
      evaluate the catalytic performance over the synthesized Co-based oxide catalysts,
      and the effect of morphological transformation on the catalytic activity is
      further confirmed via using TEM, H2-TPR, XPS, Raman spectroscopy and in situ
      Raman spectroscopy. As a proof of concept application, core-shell Co3O4 NAs-8
      presenting hierarchical nanosheets@nanoneedle arrays with a low density of
      nanoneedles exhibits the highest catalytic activity and long-term stability due
      to its low-temperature reducibility, the lattice distortion of the spinel
      structure and the abundance of surface-adsorbed oxygen (Oads). It is confirmed
      that CO oxidation on the surface of Co3O4 can proceed through the Langmuir
      Hinshelwood mechanism via using in situ Raman spectroscopy. It is expected that
      the in situ synthesis of well-defined Co3O4 monolithic catalysts can be extended
      to the development of environmentally-friendly and highly active integral
      materials for practical industrial catalysis.

PMID- 29658018
TI  - Combining photoredox and silver catalysis for azidotrifluoromethoxylation of
      styrenes.
AB  - The first example of an azidotrifluoromethoxylation of styrenes has been achieved
      by synergistic visible-light-mediated photoredox and silver catalysis.
      Trifluoromethyl arylsulfonate (TFMS) and the Zhdankin reagent were used as the
      trifluoromethoxylation reagent and the azide source, respectively. A good
      functional group tolerance and mild reaction conditions of this method are
      applicable to late-stage azidotrifluoromethoxylation of complex small molecules.
      Furthermore, the mechanistic investigations indicate the single-electron transfer
      involved in the reaction.

PMID- 29658019
TI  - Accurate theoretical characterization of dioxygen difluoride: a problem resolved.
AB  - Dioxygen difluoride is a tough molecule that has defied accurate theoretical
      description for many decades. In the present work we have identified the reason
      for this resistance: the flatness of the OO, and more important OF, stretching
      potential energy curves, which make it difficult to localise the global minimum.
      It is not related to the weak multi-reference character. Using high-level CCSD(T)
      F12/VTZ-F12 ab initio theory, the global minimum has been properly located and
      vibrationally averaged bond lengths obtained. These vibrationally averaged
      parameters agree with experimental data to within 0.01 A. Averaging was found
      essential to achieve this unprecedented accuracy. We have then simulated the IR
      and UV spectra, which compare well with experimental data and permit
      identification of the observed transitions.

PMID- 29658020
TI  - Human plasma proteome association and cytotoxicity of nano-graphene oxide grafted
      with stealth polyethylene glycol and poly(2-ethyl-2-oxazoline).
AB  - Polyethylene glycol (PEG) is a gold standard against protein fouling. However,
      recent studies have revealed surprising adverse effects of PEG, namely its
      immunogenicity and shortened bio-circulation upon repeated dosing. This
      highlights a crucial need to further examine 'stealth' polymers for controlling
      the protein 'corona', a new challenge in nanomedicine and bionanotechnology.
      Poly(2-ethyl-2-oxazoline) (PEtOx) is another primary form of stealth polymer
      that, despite its excellent hydrophilicity and biocompatibility, has found
      considerably less applications compared with PEG. Herein, we performed label-free
      proteomics to compare the associations of linear PEG- and PEtOx-grafted nano
      graphene oxide (nGO) sheets with human plasma proteins, complemented by
      cytotoxicity and haemolysis assays to compare the cellular interactions of these
      polymers. Our data revealed that nGO-PEG enriched apolipoproteins, while nGO
      PEtOx displayed a preferred binding with pro-angiogenic and structural proteins,
      despite high similarities in their respective top-10 enriched proteins. In
      addition, nGO-PEG and nGO-PEtOx exhibited similar levels of enrichment of
      complement proteins. Both PEG and PEtOx markedly reduced nGO toxicity to HEK 293
      cells while mitigating nGO haemolysis. This study provides the first detailed
      profile of the human plasma protein corona associated with PEtOx-grafted
      nanomaterials and, in light of the distinctions of PEtOx in chemical
      adaptability, in vivo clearance and immunogenicity, validates the use of PEtOx as
      a viable stealth alternative to PEG for nanomedicines and bionanotechnologies.

PMID- 29658021
TI  - Mechanistic studies on the palladium-catalyzed cross-dehydrogenative coupling of
      4-phenoxy-2-coumarins: experimental and computational insights.
AB  - Delineating the mechanistic features of C-H activation in aryl-heteroaryl
      coupling is an important step in the design of selective, catalytic processes.
      Herein we use the intramolecular dehydrogenative coupling of 4-phenoxy-2
      coumarins as a model study. Computational results and experimental studies
      suggest that CMD is operative in the cleavage of both C-H bonds, and that the
      heteroaryl C-H is cleaved initially.

PMID- 29658022
TI  - An alkaline-resistant Ag(i)-anchored pyrazolate-based metal-organic framework for
      chemical fixation of CO2.
AB  - An alkaline-resistant Ag(i)-anchored metal-organic framework has been achieved
      via postsynthetic modification of pyrazolate-based linkers. For the first time,
      the resultant MOF was completely heterogeneous and recyclable over at least ten
      cycles in cyclic carboxylation of propargyl amines and CO2 into oxazolidinones
      and tetramic acids under atmospheric pressure of CO2.

PMID- 29658023
TI  - Biodistribution studies of ultrasmall silicon nanoparticles and carbon dots in
      experimental rats and tumor mice.
AB  - Ultrasmall clearable nanoparticles possess enormous potential as cancer imaging
      agents. In particular, biocompatible silicon nanoparticles (Si NPs) and carbon
      quantum dots (CQDs) hold great potential in this regard. Their facile surface
      functionalization easily allows the introduction of different labels for in vivo
      imaging. However, to date, a thorough biodistribution study by in vivo positron
      emission tomography (PET) and a comparative study of Si vs. C particles of
      similar size are missing. In this contribution, ultrasmall (size <5 nm) Si NPs
      and CQDs were synthesized and characterized by high-resolution transmission
      electron microscopy (HR-TEM), Fourier-transform infrared (FTIR), absorption and
      steady-state emission spectroscopy. Subsequent functionalization of NPs with a
      near-infrared dye (Kodak-XS-670) or a radiolabel (64Cu) enabled a detailed in
      vitro and in vivo study of the particles. For radiolabeling experiments, the
      bifunctional chelating agent S-2-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane
      1,4,7-triacetic acid (p-SCN-Bn-NOTA) was conjugated to the amino surface groups
      of the respective NPs. Efficient radiolabeling of NOTA-functionalized NPs with
      the positron emitter 64Cu was found. The biodistribution and PET studies showed a
      rapid renal clearance from the in vivo systems for both variants of the
      nanoparticles. Interestingly, the different derivatives investigated exhibited
      significant differences in the biodistribution and pharmacokinetic properties.
      This can mostly be attributed to different surface charge and hydrophilicity of
      the NPs, arising from the synthetic strategy used to prepare the particles.

PMID- 29658025
TI  - Metallophthalocyanine-based redox active metal-organic conjugated microporous
      polymers for OER catalysis.
AB  - We report the design and synthesis of two Co2+ and Zn2+ phthalocyanine (PC)-based
      redox active metal-organic conjugated microporous polymers (MO-CMP), CoCMP and
      ZnCMP, respectively, obtained by a Schiff base condensation reaction. CoCMP,
      where Co2+ is stabilized by N4-coordination of PC, has shown stable and efficient
      electrocatalytic activity towards the OER with a low overpotential of 340 mV.

PMID- 29658026
TI  - Oral administration of rutile and anatase TiO2 nanoparticles shifts mouse gut
      microbiota structure.
AB  - The widespread application of TiO2 nanoparticles (NPs) as additives in foods such
      as gum, candy and puddings has dramatically increased the human ingestion and
      accumulation of these nanomaterials. Although the toxicity of TiO2 NPs has been
      extensively studied, their impact on gut microbiota in vivo still needs further
      research. In this study, TiO2 NPs with two main crystalline phases anatase and
      rutile were orally administrated to mice for 28 days. The dynamic influences of
      anatase and rutile on gut microbiota structures were investigated at doses
      equivalent to those consumed by people who love to eat candies. The results
      showed that titanium accumulated in the spleen, lung, and kidney but had no
      significant effects on organ histology. Gavage of rutile NPs but not anatase NPs
      resulted in longer intestinal villi and irregular arrangement of villus
      epithelial cells. Treatment with TiO2 NPs did not decrease gut microbiota
      diversity but shifted their structures in a time-dependent manner. Rutile NPs had
      a more pronounced influence on the gut microbiota than anatase NPs. The most
      influenced phylum was Proteobacteria, which was significantly increased by rutile
      but not by anatase. At the genus level, Prevotella was significantly decreased by
      both the TiO2 NPs, Rhodococcus was enriched by rutile NPs, and Bacteroides was
      increased by anatase NPs. Overall, these results suggested that chronic
      overconsumption of TiO2 NP-containing foods is likely to deteriorate the
      gastrointestinal tract and change the structures of microbiota. The crystalline
      phases may play an important role in mediating the intestinal impact of TiO2 NPs.

PMID- 29658028
TI  - Outstanding Reviewers for Integrative Biology in 2017.

PMID- 29658027
TI  - Acid- and reduction-sensitive micelles for improving the drug delivery efficacy
      for pancreatic cancer therapy.
AB  - One of the major challenges in anticancer therapy is the poor penetration of
      anticancer drugs into tumors, especially in solid tumors, resulting in decreased
      therapeutic efficacy in vivo. To solve some of these problems, in this study, a
      dual-responsive polymeric micellar system has been developed. This system
      exhibits an ultrasensitive response to the change of pH value from the
      extracellular environment to the intracellular environment, resulting in micellar
      swelling in cancer cells via the proton sponge effect. Moreover, once the swelled
      micelles escape from the lysosomes in cancer cells, the disulfide linkages are
      ruptured by GSH in the cytoplasm, leading to the rapid release of the
      encapsulated drugs into the cellular nuclei. The antitumor activity in pancreatic
      tumor-bearing mice reveals that this dual-responsive drug delivery system
      possesses a long blood circulation time and can significantly promote cell
      internalization and intracellular drug release, achieving a high anticancer
      efficacy with fewer side effects for normal tissues.

PMID- 29658029
TI  - In vitro lipid digestion in raw and roasted hazelnut particles and oil bodies.
AB  - Previous studies have proved that the physical encapsulation of nutrients by the
      cell walls of plant foods modulates macronutrient bioaccessibility during human
      digestion. In this study, we investigated structural factors that modulate lipid
      hydrolysis during in vitro digestion of raw and roasted hazelnut particles and
      isolated oil bodies. Isolated oil bodies exhibited a significantly higher lipid
      hydrolysis compared to hazelnut particles. Moreover, roasting had an impact on
      the structure of hazelnut cell walls implying a more efficient diffusion of
      digestive fluids and enzymes into the hazelnut cells. Heat treatment also caused
      destabilization of oil body interfacial protein membranes, facilitating their
      proteolysis under gastric conditions, altering the emulsion properties and
      enhancing fatty acid release during intestinal digestion. This study underlined
      the barrier role played by the plant cell wall as well as the impact of heat
      processing on lipid bioaccessibility in hazelnuts.

PMID- 29658030
TI  - Large-scale fabrication of free-standing and sub-MUm PDMS through-hole membranes.
AB  - Free-standing polydimethylsiloxane (PDMS) through-hole membranes have been
      studied extensively in recent years for chemical and biomedical applications.
      However, robust fabrication of such membranes with sub-MUm through-holes, and at
      a sub-MUm thickness over large areas is challenging. In this paper, we report a
      robust and simple method for large-scale fabrication of free-standing and sub-MUm
      PDMS through-hole membranes, combining soft-lithography with reactive plasma
      etching techniques. First, arrays of sub-MUm photoresist (PR) columns were
      patterned on another spin-coated sacrificial PR layer, using conventional
      photolithography processes. Subsequently, a solution of PDMS : hexane at a 1 : 10
      ratio was spin-coated over these fabricated arrays. The cured PDMS membrane was
      etched in a plasma mixture of sulfur hexafluoride (SF6) and oxygen (O2) to open
      the through-holes. This PDMS membrane can be smoothly released with a supporting
      ring by completely dissolving the sacrificial PR structures in acetone. Using
      this fabrication method, we demonstrated the fabrication of free-standing PDMS
      membranes at various sub-MUm thicknesses down to 600 +/- 20 nm, and nanometer
      sized through-hole (810 +/- 20 nm diameter) densities, over areas as large as 3
      cm in diameter. Furthermore, we demonstrated the potential of the as-prepared
      membranes as cell-culture substrates for biomedical applications by culturing
      endothelial cells on these membranes in a Transwell-like set-up.

PMID- 29658032
TI  - Silver triflate/p-TSA co-catalysed synthesis of 3-substituted isocoumarins from 2
      alkynylbenzoates.
AB  - In this paper, we describe the silver triflate/p-toluenesulfonic acid co
      catalysed synthesis of seventeen isocoumarins and two thieno[2,3-c]pyran-7-ones
      starting from 2-alkynylbenzoates and 3-alkynylthiophene-2-carboxylates,
      respectively. The reaction proceeds with absolute regioselectivity under mild
      reaction conditions and low catalyst loading, to afford the desired products in
      good to excellent yields. A conceivable reaction mechanism is proposed and
      supported by isotope-exchange tests, 1H NMR studies and ad hoc experiments.

PMID- 29658031
TI  - Fully automated, on-site isolation of cfDNA from whole blood for cancer therapy
      monitoring.
AB  - The potential utility of circulating tumour DNA (ctDNA) in patient blood for
      cancer diagnostics and real-time monitoring of disease progression is highly
      recognized. However, the lack of automated and efficient methods for cell-free
      DNA (cfDNA) isolation from peripheral blood has remained a challenge for broader
      acceptance of liquid biopsy in general clinical settings. Here, we demonstrate a
      lab-on-a-disc system equipped with newly developed, electromagnetically actuated,
      and reversible diaphragm valves that allows fully automated and rapid (<30 min)
      isolation of cfDNA from whole blood (>3 ml) to achieve high detection sensitivity
      by minimizing the degradation of fragile ctDNA as well as contamination of wild
      type DNA from abundant blood cells. As a proof of concept study, we used the lab
      on-a-disc to isolate cfDNA from patients with non-small cell lung cancer and
      successfully detected epidermal growth factor receptor gene mutations (L858R,
      T790M) during targeted drug therapy. The proposed lab-on-a-disc enables a fully
      automated, rapid, and point-of-care cfDNA enrichment starting from whole blood to
      facilitate the wide use of liquid biopsy in routine clinical practice.

PMID- 29658033
TI  - Metal-free oxidative coupling of quinoxalin-2(1H)-ones with arylaldehydes leading
      to 3-acylated quinoxalin-2(1H)-ones.
AB  - A facile TBHP-mediated direct oxidative coupling of quinoxalin-2(1H)-ones with
      arylaldehydes has been developed under metal-free conditions. This method
      provided a convenient and efficient approach to various 3-acylated quinoxalin
      2(1H)-ones from readily available starting materials with excellent
      regioselectivity. This reaction proceeded efficiently under mild conditions over
      a broad range of substrates and with functional group tolerance.

PMID- 29658034
TI  - Generation of 3-dimensional multi-patches on silica particles via printing with
      wrinkled stamps.
AB  - A simple route towards patchy particles with anisotropic patches with respect to
      a different functionality and directionality is presented. This method is based
      on microcontact printing of positively charged polyethylenimine (PEI) on silica
      particles using wrinkled stamps. Due to the wrinkled surface, the number of
      patches on the particles as well as the distance between two patches can be
      controlled.

PMID- 29658035
TI  - 1-Bromoethene-1-sulfonyl fluoride (1-Br-ESF), a new SuFEx clickable reagent, and
      its application for regioselective construction of 5-sulfonylfluoro isoxazoles.
AB  - A new fluorosulfonylation reagent 1-bromoethene-1-sulfonyl fluoride was developed
      (1-Br-ESF). This unique reagent possesses three addressable handles (vinyl,
      bromide, and sulfonyl fluoride) and has great potential to function as a tris
      electrophile and as a sulfur(vi) fluoride exchange (SuFEx) clickable material to
      enrich the SuFEx tool cabinet. The application of this reagent for regioselective
      synthesis of 5-sulfonylfluoro isoxazoles has been realized through a [3+2]
      cycloaddition with N-hydroxybenzimidoyl chlorides. This practical protocol
      provides a general and direct route to functionalized isoxazoles possessing
      sulfonyl fluoride moieties.

PMID- 29658036
TI  - Spirocyclic germanes via transannular insertion reactions of vinyl germylenes
      into Si-Si bonds.
AB  - The reactions of two cyclic germylene phosphane adducts with monosubstituted
      acetylenes caused the formation of spirocyclic germanes, which is postulated to
      occur by double acetylene insertion into germylene attached bonds. Further
      insertion of the formed cyclic divinylgermylene into transannular Si-Si or Si-Ge
      bonds provides the spirocyclic germanes. Thermal treatment of two
      germacyclopropenes, formed by the reaction of the two cyclic germylene phosphane
      adducts with tolane, also produced spirocyclogermanes. The structures of the
      latter require, however, a more complicated mechanistic proposal.

PMID- 29658037
TI  - Phase diagram and oxygen-vacancy ordering in the CeO2-Gd2O3 system: a theoretical
      study.
AB  - We present the phase diagram of Ce1-xGdxO2-x/2 (CGO), calculated by means of a
      combined Density Functional Theory (DFT), cluster expansion and lattice Monte
      Carlo approach. We show that this methodology gives reliable results for the
      whole range of concentrations (x = xGd <= 1). In the thermodynamic equilibrium,
      we observe two transitions: the onset of oxygen-vacancy (O-Va) ordering at ca.
      1200-3300 K for concentrations xGd = 0.3-1, and a phase separation into CeO2 and
      C-type Gd2O3 occurring below ca. 1000 K for all concentrations. We also model
      'quenched' systems, with cations immobile below 1500 K, and observe that the
      presence of random-like cation configurations does not prevent C-type vacancy
      ordering. The obtained transition temperatures for Va ordering agree rather well
      with existing experimental data. We analyse the effect of vacancy ordering and
      composition on the lattice parameters and relaxation pattern of cations.

PMID- 29658038
TI  - A giant 90-nucleus silver cluster templated by hetero-anions.
AB  - A 90-nucleus silver cluster (SD/Ag38) cocapped by tBuC6H4S- and PhCOO- ligands
      was synthesized using hetero-anion template method. Single-crystal X-ray
      diffraction (SCXRD) revealed a 90-nucleus metallic dumbbell-like core constructed
      by two large W5O19@Ag38 heads sandwiching one slender (SO4)2@Ag14 waist. Both
      W5O198- and SO42- templates were in situ generated and synergistically induced
      the formation of the largest known anion-templated silver cluster. Although
      SD/Ag38 is emission-silent at room temperature, increasingly brighter near
      infrared (NIR) emission at ca. 742 nm was detected on cooling from 293 to 93 K.

PMID- 29658040
TI  - Enhancing radical molecular beams by skimmer cooling.
AB  - A high-intensity supersonic beam source has been a key component in studies of
      molecular collisions, molecule-surface interaction, chemical reactions, and
      precision spectroscopy. However, the molecular density available for experiments
      in a downstream science chamber is limited by skimmer clogging, which constrains
      the separation between a valve and a skimmer to at least several hundred nozzle
      diameters. A recent experiment (Sci. Adv., 2017, 3, e1602258) has introduced a
      new strategy to address this challenge: when a skimmer is cooled to a temperature
      below the freezing point of the carrier gas, skimmer clogging can be effectively
      suppressed. We go beyond this proof-of-principle work in several key ways.
      Firstly, we apply the skimmer cooling approach to discharge-produced radical and
      metastable beams entrained in a carrier gas. We also identify two different
      processes for skimmer clogging mitigation-shockwave suppression at temperatures
      around the carrier gas freezing point and diffusive clogging at even lower
      temperatures. With the carrier clogging removed, we now fully optimize the
      production of entrained species such as hydroxyl radicals, resulting in a gain of
      30 in density over the best commercial devices. The gain arises from both
      clogging mitigation and favorable geometry with a much shorter valve-skimmer
      distance.

PMID- 29658039
TI  - Enantioselective palladium-catalyzed allylic alkylation reactions in the
      synthesis of Aspidosperma and structurally related monoterpene indole alkaloids.
AB  - Covering: up to the end of 2017 Enantioselective Pd-catalyzed allylic alkylations
      of prochiral enolates represent a powerful tool for the construction of all
      carbon quaternary stereocenters. This review describes the emergence of such
      reactions as strategic linchpins that enable efficient, stereocontrolled
      syntheses of Aspidosperma and related monoterpene indole alkaloids.

PMID- 29658041
TI  - Real-time monitoring of the Trojan-horse effect of silver nanoparticles by using
      a genetically encoded fluorescent cell sensor.
AB  - Silver nanoparticles (AgNPs) are widely incorporated into commercial products due
      to their antimicrobial properties. As a consequence, concerns about the adverse
      effects induced by AgNPs to humans and the environment need to be carefully
      examined. The existing literature reveals that AgNPs exhibit certain toxic
      effects, but it remains to be proved whether AgNPs or the ionic silver (Ag+)
      released from AgNPs are the main toxic species. Here, a genetically encoded
      fluorescent protein sensor with high affinity to Ag+ was developed. The resulting
      sensor, MT2a-FRET, was found to be ratiometric, sensitive and selective toward
      only Ag+ but inert against AgNPs. This makes this sensor a potential useful tool
      for monitoring the real-time intracellular dissolutions of AgNPs. Our data
      supported that AgNPs display the "Trojan-horse" mechanism, where AgNPs are
      internalized by cells and undergo dissolution intracellularly. We further found
      that cells exhibited a detoxification ability to remove active Ag+ from cells in
      48 hours.

PMID- 29658042
TI  - A pair of new chiral polyoxovanadates with decent NLO properties.
AB  - Two pure enantiomers of polyoxovanadate clusters [(l-/d-C4O6H2)2V4O8].2C6N2H18
      (abbreviated as 1-L and 1-D) have been synthesized by a two-step method. During
      the two-step synthesis process, we first carried out the solvothermal synthesis
      and then evaporated the solvent, ending up with orange-yellow crystals. The
      unique chiral architectures are built up by a single chiral ligand (tartaric
      acid) and polyoxovanadium. The chiralities of the products were confirmed by
      circular dichroism (CD) spectra. Due to the presence of protonated free
      tetramethyl ethylenediamine (TMEDA) cations, the adjacent clusters and TMEDA
      cations can be connected by hydrogen-bonding interactions. The {V4} cluster
      linked adjacent clusters via hydrogen bonds to form a 3D supramolecular network.
      The open aperture Z-scan spectra of two compounds show that molecular TPA cross
      section sigma of 1-L and 1-D are 1412 and 1094 GM, respectively, which illustrate
      that they feature decent third-order NLO properties and may have great potential
      applications as NLO materials.

PMID- 29658043
TI  - In situ follow-up of hybrid alginate-silicate microbeads formation by linear
      rheology.
AB  - Hybrid alginate-silicate microbeads of about 10-20 MUm were synthesized by
      combining alginate crosslinking, silica condensation in a one pot approach using
      a food grade emulsion as template. A fine tuning of the formulation composition
      (alginate, silica and calcium sources) is necessary in order to obtain core-shell
      microbeads instead of unshaped and irregular fragments or even perforated
      spherical beads. Importantly, in situ linear rheology provides insights into the
      reaction mechanism as a result of the rheological fingerprint profile obtained
      during beads formation.

PMID- 29658044
TI  - Unique and contrasting structures of homoleptic lanthanum(iii) and cerium(iii)
      3,5-dimethylpyrazolates.
AB  - Homoleptic [La(Me2pz)3]n (Me2pz = 3,5-dimethylpyrazolato) is a MU-eta2:eta5-Me2pz
      coordination polymer with 12-coordinate La atoms in an unusual eta5:eta5 Me2pz
      sandwich, whilst the cerium congener forms a molecular tetrametallic cage
      [Ce4(Me2pz)12] featuring six different Me2pz coordination modes.

PMID- 29658045
TI  - Potential of Borojoa patinoi Cuatrecasas water extract to inhibit nosocomial
      antibiotic resistant bacteria and cancer cell proliferation in vitro.
AB  - Borojo (Borojoa patinoi Cuatrec.) is a fruit used in Colombian traditional
      medicine with supposed antihypertensive, antitumoral, diuretic, healing,
      immunological, anti-inflammatory and aphrodisiac effects. To explore the relative
      merits in terms of biological activities of borojo aqueous extract (BAE), we
      investigated in vitro its antimicrobial activity on nosocomial pathogenic and
      multidrug resistant (MDR) strains of Pseudomonas aeruginosa (6), Staphylococcus
      aureus (1) and Candida species (6), as well as its cytotoxicity on human
      conjunctive Wong-Kilbourne derivative (WKD) cells and Caco-2 cells from
      heterogeneous human epithelial colorectal adenocarcinoma. The bacteriostatic
      activity was observed overall on P. aeruginosa strains, as evidenced by the
      increase of the lag phase (43 hours) and reduction of the maximum growth rate
      detected using 187.5 mg BAE per mL. The bactericidal activity, instead, was
      observed at 375 mg BAE per mL. On the other hand, BAE showed an anti
      proliferative effect against the Caco-2 cell line and was shown to be toxic on
      the WKD cell line at concentrations ranging from 0.05 to 187.5 MUg mL-1. The
      analysis of the phenolic fraction of the fruit aqueous extract (BAE) using UHPLC
      MS/MS showed the presence of 26 compounds, with vanillic, syringic and o-coumaric
      acids as the most abundant. Among these molecules, 7.81 ng mL-1 luteolin and
      myricetin, singly tested, were able to reduce bacterial growth. To the best of
      our knowledge, we are unaware of any previous studies demonstrating the anti
      bacterial activity of borojo aqueous extract against antibiotic resistant strains
      of P. aeruginosa, and its anti-proliferative effect against WKD and Caco-2 cell
      lines. The latter result offers a potential base for new interest and
      investigations in relation to colon carcinoma models and borojo fruit
      consumption, since in Colombia this fruit is consumed also for its supposed
      antitumoral effects.

PMID- 29658046
TI  - One-dimensional hierarchical MoO2-MoSx hybrids as highly active and durable
      catalysts in the hydrogen evolution reaction.
AB  - The hydrogen evolution reaction (HER) is a fundamental process in
      electrocatalysis and plays an important role in energy conversion through water
      splitting to produce hydrogen. Finding highly effective and scalable HER
      catalysts is becoming a very urgent task. In this work, we developed a facile
      method to synthesize a one-dimensional hierarchical MoO2-MoSx hybrid
      electrocatalyst via the calcination of a one-dimensional (1D) organic-inorganic
      MoO3-EDA precursor. The obtained MoO2-MoSx hybrids deliver a low onset potential
      of 155 mV, a low Tafel slope of 51.6 mV dec-1 and excellent cycling stability in
      acidic electrolytes, suggesting high electrocatalytic activity. Furthermore, MoO2
      MoS2 exhibited high cycling stability even after 10 h of continuous operation
      under high overpotential; the current density still remained unchanged. The
      enhanced HER performances are likely due to high conductivity and more exposed
      active sites and the effective integration of MoO2 and MoSx. In a word, these
      results fully demonstrated that 1D nanostructured MoO2-MoSx hybrid materials may
      have great potential in future clean energy applications.

PMID- 29658047
TI  - A structural comparison of casein micelles in cow, goat and sheep milk using X
      ray scattering.
AB  - The casein micelle is a flexible construct, with its key structural components
      being casein proteins and colloidal calcium phosphate nanoclusters. According to
      literature, milk from different species exhibits differences in composition and
      physicochemical properties. X-ray scattering techniques were used to investigate
      and compare the nanoscale structure of casein micelles present in cow, goat and
      sheep milk. Although there were differences in the size and density of larger
      scale protein structures, at an atomic level the protein structures were similar.
      There were also strong similarities in the structure of the calcium-containing
      nanoclusters, namely that they had similar sizes and separations within the
      casein micelle for all three species.

PMID- 29658048
TI  - Chromium chains as polydentate fluoride ligands for actinides and group IV
      metals.
AB  - The reactions of {Cr6} horseshoe chains {[nPr2NH2]3[Cr6F11(O2CtBu)10]}2, 1 and
      precursors of actinides and group IV metals led to a series of ring complexes
      [nPr2NH2][Cr7TiF6O2(O2CtBu)16], 2, [nPr2NH2][Cr6Ti2F5O3(O2CtBu)16], 3,
      [Cr6ThF7(O2CtBu)15 (Me2SO)], 4, [(nPr2NH2)2(Cr6Th2F12(O2CtBu)16)], 5 and
      [nPr2NH2][Cr6U2O2F8(O2CtBu)16(Me2SO)], 6. X-ray structure studies indicate that
      the {Cr6} chains maintain their structures in these complexes, acting as
      polydentate fluoride ligands. Their static magnetic properties were measured and
      fitted by isotropic exchange Hamiltonian. In accordance with 1, the magnetic
      exchanges between CrIII are antiferromagnetic, while the exchange interactions
      can be modified by the tetravalent metals. For compound 6, ferromagnetic
      exchanges JCr-U and JU-U are obtained. EPR spectra of compounds 2-5 were measured
      at Q band and were simulated. The spectrum of 2 has the same profile as {Cr7Cd}
      and {Cr7Zn} rings with a ground state S = 3/2. 3, 4 and 5 give similar EPR
      spectra with S = 0 ground states.

PMID- 29658049
TI  - A simple microfluidic platform for rapid and efficient production of the
      radiotracer [18F]fallypride.
AB  - Herein, we report the development of a simple, high-throughput and efficient
      microfluidic system for synthesizing radioactive [18F]fallypride, a PET imaging
      radiotracer widely used in medical research. The microfluidic chip contains all
      essential modules required for the synthesis and purification of radioactive
      fallypride. The radiochemical yield of the tracer is sufficient for multiple
      animal injections for preclinical imaging studies. To produce the on-chip
      concentration and purification columns, we employ a simple "trapping" mechanism
      by inserting rows of square pillars with predefined gaps near the outlet of
      microchannel. Microspheres with appropriate functionality are suspended in
      solution and loaded into the microchannels to form columns for radioactivity
      concentration and product purification. Instead of relying on complicated flow
      control elements (e.g., micromechanical valves requiring complex external
      pneumatic actuation), external valves are utilized to control transfer of the
      reagents between different modules. The on-chip ion exchange column can
      efficiently capture [18F]fluoride with negligible loss (~98% trapping
      efficiency), and subsequently release a burst of concentrated [18F]fluoride to
      the reaction cavity. A thin layer of PDMS with a small hole in the center
      facilitates rapid and reliable water evaporation (with the aid of azeotropic
      distillation and nitrogen flow) while reducing fluoride loss. During the solvent
      exchange and fluorination reaction, the entire chip is uniformly heated to the
      desired temperature using a hot plate. All aspects of the [18F]fallypride
      synthesis were monitored by high-performance liquid chromatography (HPLC)
      analysis, resulting in labelling efficiency in fluorination reaction ranging from
      67-87% (n = 5). Moreover, after isolating unreacted [18F]fluoride, remaining
      fallypride precursor, and various by-products via an on-chip purification column,
      the eluted [18F]fallypride is radiochemically pure and of a sufficient quantity
      to allow for PET imaging (~5 mCi). Finally, a positron emission tomography (PET)
      image of a rat brain injected with ~300 MUCi [18F]fallypride produced by our
      microfluidic chip is provided, demonstrating the utility of the product produced
      by the microfluidic reactor. With a short synthesis time (~60 min) and a highly
      integrated on-chip modular configuration that allows for concentration, reaction,
      and product purification, our microfluidic chip offers numerous exciting
      advantages with the potential for applications in radiochemical research and
      clinical production. Moreover, due to its simplicity and potential for
      automation, we anticipate it may be easily integrated into a clinical
      environment.

PMID- 29658050
TI  - Aggregation Pheromone of the Bearded Weevil, Rhinostomus barbirostris
      (Coleoptera: Curculionidae): Identification, Synthesis, Absolute Configuration
      and Bioactivity.
AB  - The bearded weevil, Rhinostomus barbirostris (Coleoptera: Curculionidae:
      Dryophthorinae), attacks coconut trees, oil palms and other species of Arecaceae.
      Besides direct damage, R. barbirostris may be a vector of diseases in coconut and
      oil palms, such as stem bleeding (resinosis) and red ring disease. Currently, the
      only method to control this weevil is by visual observation of damage and removal
      of infected plants. Semiochemical-based trapping could improve the effectiveness
      of monitoring and management of R. barbirostris. In comparisons of volatiles
      released by R. barbirostris males and females by gas chromatography (GC) two male
      specific compounds were observed. GC-mass spectrometry (MS) and GC-Fourier
      transform-infrared (FTIR) analyses of the natural compounds suggested these were
      diastereoisomers of 5-hydroxy-4-methylheptan-3-one, also known as sitophilure, a
      pheromone component of other dryophthorine species. Synthesis of the mixture of
      all four stereoisomers of sitophilure was performed in two steps, and the
      chemical structures were confirmed by comparing GC retention times and MS and
      FTIR spectra of natural and synthetic compounds. The absolute configurations of
      the two male-specific compounds were elucidated by enantioselective GC; the major
      component was the (4S,5R)-isomer, and the minor component (4S,5S)-sitophilure. In
      analyses by GC-electroantennography (EAG) the antennae of male and female R.
      barbirostris only responded to the (4S,5R)-isomer of the synthetic sitophilure.
      The stereoisomeric mixture of sitophilure was attractive to both sexes of R.
      barbirostris in laboratory experiments in the presence of sugar cane volatiles,
      and a similar result was obtained in a preliminary field trapping test.

PMID- 29658051
TI  - Strategies to enhance the production of pinoresinol and its glucosides by
      endophytic fungus (Phomopsis sp. XP-8) isolated from Tu-chung bark.
AB  - To improve the production yield of (+)-pinoresinol (Pin), (+)-pinoresinol
      monoglucoside (PMG), and (+)-pinoresinol diglucoside (PDG), different methods
      were conducted, including co-culture with resveratrol-producing Alternaria sp.
      MG1 spores and addition of Tu-chung in a medium at the start of cultivation,
      ultrasound treatment (40 kHZ, 10 min) on 5-day culture, and addition of ethanol
      and sodium butyrate on Day 3, followed by cultivation for an additional period of
      2 days. At the end of the cultivation period (5 days), the liquid phase was
      collected for product analysis. Cells were collected for the determination of
      gene expression levels and then used in bioconversion using resting cells for
      another period of 2 days. The liquid phase was measured to determine the output
      of the target products and the expression levels of the key genes related to the
      biosynthesis of these compounds. Consequently, co-culture with Alternaria MG1 and
      addition of Tu-chung bark in the medium efficiently increased Pin, PMG, and PDG
      production yield in the biosynthesis systems using potato dextrose broth medium
      and resting cells of Phomopsis sp. XP-8. The key genes related to the
      biosynthesis of these compounds were significantly upregulated. However, in the
      majority of cases, the addition of ethanol and sodium butyrate, and ultrasound
      treatment decreased the production yield of Pin, PMG, and PDG. The change in
      production yield was not consistently accompanied by a change in gene expression.

PMID- 29658052
TI  - Reduced alphaGlcNAc glycosylation on gastric gland mucin is a biomarker of
      malignant potential for gastric cancer, Barrett's adenocarcinoma, and pancreatic
      cancer.
AB  - Gastric gland mucin secreted from pyloric gland cells, mucous neck cells, and
      cardiac gland cells of the gastric mucosa harbors unique O-glycans carrying
      terminal alpha1,4-linked N-acetylglucosamine residues (alphaGlcNAc), which are
      primarily attached to the scaffold mucin core protein MUC6. alphaGlcNAc acts as
      an antibiotic against Helicobacter pylori (H. pylori), a microbe causing gastric
      cancer. In addition, mice deficient in A4gnt, which encodes the enzyme alpha1,4-N
      acetylglucosaminyltransferase (alpha4GnT) that catalyzes alphaGlcNAc
      biosynthesis, spontaneously develop gastric differentiated-type adenocarcinoma,
      even if not infected by H. pylori. Thus, alphaGlcNAc prevents gastric cancer as
      both an antibiotic and a tumor suppressor (Nakayama in Acta Histochem Cytochem
      47:1-9, 2014b). Indeed, in humans alphaGlcNAc loss on MUC6 in differentiated-type
      adenocarcinoma is closely associated with poor patient prognosis (Shiratsu et al.
      in Cancer Sci 105:126-133, 2014). Recently, we reported reduced alphaGlcNAc
      expression on MUC6 in both pyloric gland adenoma of the stomach and chronic
      atrophic gastritis, in Barrett's esophagus, and in pancreatic intraductal
      papillary-mucinous neoplasm (IPMN)/pancreatic intraepithelial neoplasia (PanIN),
      all potentially premalignant conditions. This review discusses whether relatively
      reduced levels of alphaGlcNAc in these lesions could serve as a biomarker to
      predict malignant potential and cancer progression.

PMID- 29658053
TI  - Flow and air conditioning simulations of computer turbinectomized nose models.
AB  - Air conditioning for the human respiratory system is the most important function
      of the nose. When obstruction occurs in the nasal airway, turbinectomy is used to
      correct such pathology. However, mucosal atrophy may occur sometime after this
      surgery when it is overdone. There is not enough information about long-term
      recovery of nasal air conditioning performance after partial or total surgery.
      The purpose of this research was to assess if, based on the flow and
      temperature/humidity characteristics of the air intake to the choana, partial
      resection of turbinates is better than total resection. A normal nasal cavity
      geometry was digitized from tomographic scans and a model was printed in 3D.
      Dynamic (sinusoidal) laboratory tests and computer simulations of airflow were
      conducted with full agreement between numerical and experimental results.
      Computational adaptations were subsequently performed to represent six
      turbinectomy variations and a swollen nasal cavity case. Streamlines along the
      nasal cavity and temperature and humidity distributions at the choana indicated
      that the middle turbinate partial resection is the best alternative. These
      findings may facilitate the diagnosis of nasal obstruction and can be useful both
      to plan a turbinectomy and to reduce postoperative discomfort. Graphical Abstract
      ?.

PMID- 29658054
TI  - Special issue on cognitive robotics.

PMID- 29658055
TI  - Salvage chemotherapy with the combination of oxaliplatin, leucovorin, and 5
      fluorouracil in advanced gastric cancer refractory or intolerant to
      fluoropyrimidines, platinum, taxanes, and irinotecan.
AB  - BACKGROUND: Although nivolumab showed survival benefit in patients with advanced
      gastric cancer (AGC) progressing after standard chemotherapy, there is a lack of
      data regarding oxaliplatin-based chemotherapy in this clinical setting. METHODS:
      We retrospectively evaluated the efficacy and safety of oxaliplatin with l
      leucovorin and bolus/continuous infusion of 5-fluorouracil as salvage treatment
      in patients with AGC refractory or intolerant to fluoropyrimidines, cisplatin,
      taxanes, and irinotecan. RESULTS: Overall, 50 patients treated between December
      2009 and December 2013 were included in this analysis. The overall response rate
      (ORR) was 21.2% among 33 patients with measurable disease. The median time to
      treatment failure (TTF) and overall survival (OS) were 2.4 and 4.2 months. In
      multivariate analysis, factors associated with OS included poor performance
      status [hazard ratio (HR) 3.20; 95% confidence interval (CI) 1.55-6.60], shorter
      time from the start of first-line therapy (HR 2.20; 95% CI 1.18-4.12), and higher
      neutrophil/lymphocyte ratio value (HR 4.87; 95% CI 2.32-10.25). In patients (n =
      35) with at most one risk factor, the ORR, median TTF, and OS were 26.1%, 3.6,
      and 6.7 months, respectively. The most common grade 3 or 4 adverse events were
      neutropenia (30%), anemia (22%), febrile neutropenia (8%), and peripheral
      neuropathy (8%). Initial and subsequent dose reduction was performed in 18 (36%)
      and 23 (46%) patients. There was one treatment-related death caused by septic
      infection. CONCLUSIONS: Salvage chemotherapy with the combination of oxaliplatin,
      leucovorin, and 5-fluorouracil has a potential activity and is tolerable for
      heavily treated AGC with appropriate dose modification and patient selection.

PMID- 29658056
TI  - Bone toughening through stress-induced non-collagenous protein denaturation.
AB  - Bone toughness emerges from the interaction of several multiscale toughening
      mechanisms. Recently, the formation of nanoscale dilatational bands and hence the
      accumulation of submicron diffuse damage were suggested as an important energy
      dissipation processes in bone. However, a detailed mechanistic understanding of
      the effect of this submicron toughening mechanism across multiple scales is
      lacking. Here, we propose a new three-dimensional ultrastructure volume element
      model showing the formation of nanoscale dilatational bands based on stress
      induced non-collagenous protein denaturation and quantify the total energy
      released through this mechanism in the vicinity of a propagating crack. Under
      tensile deformation, large hydrostatic stress develops at the nanoscale as a
      result of local confinement. This tensile hydrostatic stress supports the
      denaturation of non-collagenous proteins at organic-inorganic interfaces, which
      leads to energy dissipation. Our model provides new fundamental understanding of
      the mechanism of dilatational bands formation and its contribution to bone
      toughness.

PMID- 29658057
TI  - Combined effects of rat Schwann cells and 17beta-estradiol in a spinal cord
      injury model.
AB  - Spinal cord injury (SCI) is a devastating traumatic event which burdens the
      affected individuals and the health system. Schwann cell (SC) transplantation is
      a promising repair strategy after SCI. However, a large number of SCs do not
      survive following transplantation. Previous studies demonstrated that 17beta
      estradiol (E2) protects different cell types and reduces tissue damage in SCI
      experimental animal model. In the current study, we evaluated the protective
      potential of E2 on SCs in vitro and investigated whether the combination of
      hormonal and SC therapeutic strategy has a better effect on the outcome after
      SCI. Primary SC cultures were incubated with E2 for 72 h. In a subsequent
      experiment, thoracic contusion SCI was induced in male rats followed by sustained
      administration of E2 or vehicle. Eight days after SCI, DiI-labeled SCs were
      transplanted into the injury epicenter in vehicle and E2-treated animals. The
      combinatory regimen decreased neurological and behavioral deficits and protected
      neurons and oligodendrocytes in comparison to vehicle rats. Moreover, E2 and SC
      significantly decreased the number of Iba-1+ (microglia) and GFAP+ cells
      (astrocyte) in the SCI group. In addition, we found a significant reduction of
      mitochondrial fission-markers (Fis1) and an increase of fusion-markers (Mfn1 and
      Mfn2) in the injured spinal cord after E2 and SC treatment. These data
      demonstrated that E2 protects SCs against hypoxia-induced SCI and improves the
      survival of transplanted SCs.

PMID- 29658059
TI  - Visceral fat area, not body mass index, predicts postoperative 30-day morbidity
      in patients undergoing colon resection for cancer.
AB  - PURPOSE: Colectomy for cancer in obese patients is technically challenging and
      may be associated with worse outcomes. Whether visceral obesity, as measured on
      computed tomography, is a better predictor of complication than body mass index
      (BMI) or determines long-term oncologic outcomes has not been well characterized.
      This study examines the association between derived anthropometrics and
      postoperative complication and long-term oncologic outcomes. METHODS:
      Retrospective review of patients undergoing elective colectomy for cancer at a
      single tertiary-care center from 2010 to 2016. Adipose tissue distribution
      measurements, including visceral fat area (VFA), were determined from
      preoperative imaging. The primary outcome was 30-day postoperative complication;
      secondary outcomes included overall and disease-free survival. Multivariable
      logistic regression was performed to determine association between obesity
      metrics and outcome. RESULTS: Two hundred and sixty-four patients underwent 266
      primary resections of colon cancer. Twenty-eight patients (10.5%) developed major
      morbidity (Clavien-Dindo grade >= III). VFA but not BMI was significantly
      associated with morbidity in multivariate analysis (p = 0.004, odds ratio 1.99,
      95% confidence interval 1.25-3.19). No other imaging-derived anthropometric was
      associated with increased morbidity. In receiver operating characteristic
      analysis, VFA was predictive of major morbidity (area under curve 0.660). A
      cutoff value of VFA >= 191 cm2 was associated with 50% sensitivity and 76%
      specificity for predicting major morbidity. Patients with VFA >= 191cm2 had 19.4%
      risk of morbidity, whereas those with < 191 cm2 had 7.2% risk (relative risk
      ratio 2.69, unadjusted p = 0.004). Neither VFA nor BMI was associated with
      overall or disease-free survival. CONCLUSION: VFA but not BMI predicts morbidity
      following elective surgery for colon cancer.

PMID- 29658060
TI  - Decompressive craniectomy in traumatic brain injury-the discussion must continue.

PMID- 29658061
TI  - Tapping the Bioactivity Potential of Residual Stream from Its Pretreatments May
      Be a Green Strategy for Low-Cost Bioconversion of Rice Straw.
AB  - In this study, it was found that the residual stream from pretreatments of rice
      straw exhibited high antioxidant activity. Assays based on the Folin-Ciocalteu
      colorimetric method confirmed that the residual stream contained large amounts of
      phenolic compounds. Three antioxidant assays were employed to evaluate the
      bioactivity of the residual stream. Strong linear correlations existed among the
      release of phenolic compounds, saccharification efficiency, and antioxidant
      activity. The alkaline pretreatment provided a much greater release of phenolic
      compounds, especially phenolic acids, compared to the acid pretreatment, and
      consequently, it had stronger linear correlations than the acid pretreatment.
      Antibacterial experiments demonstrated the ability of the phenolic compounds in
      the residual stream to inhibit the growth of microorganisms, indicating the
      potential of these compounds as antimicrobial agents. To discuss the possibility
      of the co-production of antimicrobial agents and biofuels/biochemicals, both acid
      and alkaline pretreatments were optimized using response surface methodology.
      Under the optimal conditions, 285.7 g glucose could be produced from 1 kg rice
      straw with the co-production of 3.84 g FA and 6.98 g p-CA after alkaline
      pretreatment. These results show that the recovery of phenolic compounds from the
      residual stream could be a green strategy for the low-cost bioconversion of rice
      straw.

PMID- 29658063
TI  - Effects of Modified Palygorskite Supplementation on Egg Quality and Mineral
      Element Content, and Intestinal Integrity and Barrier Function of Laying Hens.
AB  - This study was conducted to investigate effects of modified palygorskite (MPal)
      supplementation on the laying performance, egg quality and mineral element
      content, immunity, oxidative status, and intestinal integrity and barrier
      function of laying hens. A total of 360 52-week-old Hyline Brown hens were
      randomly assigned into four dietary treatments for a 7-week feeding trial. The
      birds were fed a basal diet supplemented with 0 (control group), 0.25, 0.5, and 1
      g/kg MPal, respectively. The supplementation of MPal did not alter laying
      performance and egg quality among groups. Compared with the control group, MPal
      inclusion decreased lead (Pb) content in yolks at 49 days, and either 0.5- or 1
      g/kg MPal supplementation decreased Pb accumulation in yolks at 25 days and
      manganese (Mn) accumulation in yolks at 25 and 49 days. The contents of jejunal
      secretory immunoglobulin A (SIgA), ileal SIgA, and immunoglobulin G were
      decreased by the dietary 0.5-g/kg MPal supplementation. The supplementation of
      MPal also decreased malondialdehyde content in jejunum and ileum, and decreased
      serum diamine oxidase activity of the laying hens at 25 and 49 days. The
      inclusion of 0.5 and 1 g/kg MPal enhanced villus height in jejunum and ileum, and
      also increased the ratio of villus height to crypt depth in ileum. In conclusion,
      MPal supplementation decreased Pb and Mn contents in yolks, and exhibited
      beneficial effects on the intestinal immunity, oxidative status, and intestinal
      integrity and barrier function of laying hens and its optimal dosage was 0.5
      g/kg.

PMID- 29658062
TI  - Mental health insurance access and utilization among childhood cancer survivors:
      a report from the childhood cancer survivor study.
AB  - PURPOSE: To describe and compare the prevalence of mental health access,
      preference, and use among pediatric cancer survivors and their siblings. To
      identify factors associated with mental health access and use among survivors.
      METHODS: Six hundred ninety-eight survivors in the Childhood Cancer Survivor
      Study (median age = 39.4; median years from diagnosis = 30.8) and 210 siblings
      (median age = 40.4) were surveyed. Outcomes included having mental health
      insurance coverage, delaying care due to cost, perceived value of mental health
      benefits, and visiting a mental health provider in the past year. RESULTS: There
      were no differences in mental health access, preferences, and use between
      survivors and siblings (p > 0.05). Among respondents with a history of distress,
      most reported not having seen a mental health provider in the past year (80.9%
      survivors vs. 77.1% siblings; p = 0.60). Uninsured survivors were more likely to
      defer mental health services due to cost (24.6 vs. 8.4%; p < 0.001). In
      multivariable models, males (OR = 2.96) and survivors with public (OR = 6.61) or
      employer-sponsored insurance (ESI; OR = 14.37) were more likely to have mental
      health coverage. CONCLUSIONS: Most childhood cancer survivors value having mental
      healthcare benefits; however, coverage and use of mental health services remain
      suboptimal. The most vulnerable of survivors, specifically the uninsured and
      those with a history of distress, are at risk of experiencing challenges
      accessing mental health care. IMPLICATIONS FOR CANCER SURVIVORS: Childhood cancer
      survivors are at risk for experiencing high levels of daily life stress that is
      compounded by treatment-related sequelae. Integrative, system-based approaches
      that incorporate financial programs with patient education about insurance
      benefits can help reduce some of the financial barriers survivors face.

PMID- 29658064
TI  - Allele frequencies and forensic genetic parameters of 10 supplementary and two
      CODIS loci in a Japanese population genotyped using an Investigator HDplex Kit.
AB  - A total of 344 unrelated Japanese adults were genotyped to determine allele
      frequencies and evaluate forensic parameters for 10 autosomal supplementary non
      CODIS loci and 2 autosomal CODIS loci using an Investigator(r) HDplex Kit for
      complex relationship testing.

PMID- 29658065
TI  - Humification process in different kinds of organic residue by composting and
      vermicomposting: have microbioreactors really accelerated the process?
AB  - The organic matter existing in nature presents as a complex system of various
      substances. The humic fraction refers to the humic substances (HS) and consists
      of humic acids (HA), fulvic acids (FA), and humins, according to solubility in
      aqueous solution. The physical and chemical characteristics of HA, FA, and humins
      depend on many factors, among which is the type of original organic material. Two
      processes for the stabilization of organic materials are known worldwide:
      composting and vermicomposting. Cattle manure, rice straw, sugarcane bagasse, and
      vegetable wastes from leaves were the organic residues chosen for the composting
      and vermicomposting processes. In this study, the differences between the HS
      extracted from such composted and vermicomposted residues were evaluated. The so
      extracted HS were evaluated by spectroscopy in the regions of infrared and
      ultraviolet-visible, and pyrolysis coupled with gas chromatography with mass
      spectrometric detection is applied. Thus, we expect that the results obtained
      here indicate which of the two processes is more efficient in the
      biotransformation of organic residues in a short period with respect to the HS
      content. It was also observed that the basic units of the humic fractions
      generated (although they presented different degrees of maturation) are the same.
      Altogether, the data reported here bring to light that the structures of the HS
      are very similar, differing in quantities. These results can still be
      extrapolated to several other raw materials, since the most variable organic
      matrices were used here to allow this data extrapolation. In addition, the
      process seems to lead to the formation of more aliphatic substances,
      counterpoising what is found in the literature.

PMID- 29658066
TI  - The effect of simulated acid rain on the stabilization of cadmium in contaminated
      agricultural soils treated with stabilizing agents.
AB  - Stabilization technology is one of widely used remediation technologies for
      cadmium (Cd)-contaminated agricultural soils, but stabilized Cd in soil may be
      activated again when external conditions such as acid rain occurred. Therefore,
      it is necessary to study the effect of acid rain on the performance of different
      stabilizing agents on Cd-polluted agriculture soils. In this study, Cd
      contaminated soils were treated with mono-calcium phosphate (MCP), mono-ammonium
      phosphate (MAP), and artificial zeolite (AZ) respectively and incubated 3 months.
      These treatments were followed by two types of simulated acid rain (sulfuric acid
      rain and mixed acid rain) with three levels of acidity (pH = 3.0, 4.0, and 5.6).
      The chemical forms of Cd in the soils were determined by Tessier's sequential
      extraction procedure, and the leaching toxicities of Cd in the soils were
      assessed by toxicity characteristic leaching procedure (TCLP). The results show
      that the three stabilizing agents could decrease the mobility of Cd in soil to
      some degree with or without simulated acid rain (SAR) treatment. The
      stabilization performances followed the order of AZ < MAP < MCP. Acid rain
      soaking promoted the activation of Cd in stabilized soil, and both anion
      composition and pH of acid rain were two important factors that influenced the
      stabilization effect of Cd.

PMID- 29658067
TI  - Effect of mono and divalent salts on the conformation and composition of a humic
      acid and on atrazine adsorption.
AB  - We investigated the effects of sodium and calcium chlorides on the conformation
      and composition of a purified Aldrich humic acid (PAHA), as well as on the
      adsorption of atrazine. The PAHA was treated with 1, 10, and 100 mM NaCl, CaCl2,
      or a mixture of NaCl and CaCl2 (molar ratio 5:1) at pH 7.5 and 8.5. The
      conformation of treated PAHA was characterized by atomic force microscopy (AFM)
      and transmission electron microscopy (TEM) and spectral changes of functional
      groups of PAHA by Fourier transform infrared spectroscopy (FTIR). AFM and TEM
      images showed an increase in the aggregation of the PAHA as salinity increased.
      FTIR spectra revealed that changes in the aggregation of the PAHA were
      principally due to the formation of bridged interactions between calcium and
      carboxylate groups in the PAHA. The adsorption of atrazine on > 0.45 MUm PAHA
      decreased as salt concentrations and pH increased. This reduction of atrazine
      adsorption was explained by the decrease in available adsorption sites due to
      agglomeration of PAHA.

PMID- 29658068
TI  - Application of the Mahalanobis distance on evaluating the overall performance of
      moving-grate incineration of municipal solid waste.
AB  - In this study, there were 54 municipal solid waste (MSW) moving-grate
      incineration power plants investigated in China. The flue gas emission data of
      CO, NOx, SO2, HCl, and particles were collected as monthly means directly from
      the plants for 12 consecutive months from 2011 to 2012, as well as the annual
      cumulative consumption data of activated carbon, CaO/Ca(OH)2, and #0 diesel.
      Eventually, 37 out of the 54 plants were evaluated on the overall performance
      using the Mahalanobis distance. As a result, there were 31 total outliers
      (potential errors or risks in the operation) detected from the flue gas emission
      data in 9 out of 37 plants. The results revealed that the Mahalanobis distance
      was an effective method to evaluate the overall performance of MSW moving-gate
      incineration from the massive normal-looking flue gas emission data. It was also
      illustrated that reducing the frequency of the load changes was more important
      than reducing the magnitude of the load changes, especially in the range between 
      10 and 10% of the load changes. Furthermore, the average consumption of
      activated carbon, CaO/Ca(OH)2, and #0 diesel in the MSW moving-grate incineration
      power plants was 0.32 +/- 0.13 kg, 7.75 +/- 3.06 kg, and 0.15 +/- 0.12 kg per ton
      of MSW, respectively.

PMID- 29658069
TI  - Nine prophylactic polishing pastes: impact on discoloration, gloss, and surface
      properties of a CAD/CAM resin composite.
AB  - OBJECTIVES: To investigate discoloration reduction and changes of surface
      properties of a CAD/CAM resin composite after 14 days' storage in red wine and
      polishing with nine different prophylactic polishing pastes (PPPs). MATERIALS AND
      METHODS: Rectangular discs (N = 172) were fabricated and polished (P4000) using
      GC Cerasmart (GC Europe) to investigate different polishing protocols with 1-4
      related descending PPPs (22 in total): Cleanic/CLE-Kerr, CleanJoy/CLJ-Voco, Clean
      Polish/Super Polish/SPO-Kerr, Clinpro Prophy Paste/CPP-3M, Detartrine/DET
      Septodont, Nupro/NUP-Dentsply Sirona, Prophy Paste CCS/CCS-Directa, Proxyt/PXT
      Ivoclar Vivadent, and Zircate/ZIR Prophy Paste-Dentsply Sirona. Surface
      properties (roughness values (RV)/Ra, Rz, Rv, surface free energy (SFE), surface
      gloss (G), and discoloration (DeltaE)) were analyzed before and after storage and
      additional polishing. Data were examined using Kolmogorov-Smirnov test, three-way
      ANOVA followed by Tukey-B post hoc, Mann-Whitney U, and Kruskal-Wallis H tests
      (alpha < 0.05). RESULTS: Regarding RV, CLE, followed by CCS, and CPP showed the
      highest values; the lowest presented SPO and DET (p < 0.001). No impact of PPP
      was observed on DeltaE values (p = 0.160). The lowest SFE presented DET, followed
      by SPO; highest showed CCS followed by NUP and CPP (p < 0.001). Within G, lowest
      values were observed for CLE and NUP, followed by CCS, ZIP, and CLJ (p < 0.001);
      the highest presented SPO (p < 0.001). Polishing showed generally a positive
      impact on SFE values (p < 0.001-p = 0.007), except ZIP (p = 0.322) and CLE (p =
      0.083). G increased and RV decreased after polishing (p < 0.001), except SPO,
      with no significant change for G (p = 0.786). CONCLUSIONS: Polishing with PPPs
      improves the surface properties and is generally recommended. The choice of PPP
      has a minor role in removing discolorations. Multi-step systems should be carried
      out conscientiously. CLINICAL RELEVANCE: The proper selection of PPP is essential
      for the clinical outcome of surface properties of prosthetic restorations. Not
      every polishing paste leads to the same final surface quality.

PMID- 29658070
TI  - Effect of photobiomodulation therapy on postoperative pain after endodontic
      treatment: a randomized, controlled, clinical study.
AB  - OBJECTIVE: The aim of this prospective, randomized, clinical study was to assess
      the effect of photobiomodulation therapy (PBM) with low-level laser irradiation
      (LLLI) on postoperative pain after endodontic treatment. MATERIALS AND METHODS:
      Sixty patients, diagnosed with irreversible pulpitis in lower molar teeth,
      participated in the study. All treatments were performed by a single operator.
      Participants were randomly divided into two groups: in the experimental group
      (EG), endodontic treatment was performed with a reciprocating system, immediately
      followed by PBM with LLLI; and only endodontic treatment was performed in the
      control group (CG). Postoperative pain was assessed by a second examiner, who was
      blinded, using two scales: verbal rating scale (VRS) and numerical rating scale
      (NRS). Assessment was carried out at 6, 12, and 24 h after treatment. Data were
      analyzed using chi-squared, Fisher's exact, Mann-Whitney tests, ordinal, and non
      parametric regression analyses. RESULTS: For the prevalence of pain, the
      difference between the groups was significant for the evaluations performed after
      6 h (p = 0.04) and 24 h (p = 0.02). The difference after 24 h remained
      significant after stratification by sex and extrusion of filling material.
      Increased pain intensity was associated with extrusion of root canal filling
      material to the periapical region in the two scales used. CONCLUSION: The effect
      of PBM therapy after endodontic treatment showed a significant decreasein
      prevalence of postoperative pain. CLINICAL RELEVANCE: The PBM reduces the
      prevalence of postoperative pain and may benefit patients who need endodontic
      treatment.

PMID- 29658071
TI  - Pathological Remodeling of the Myocardium in Chronic Heart Failure: Role of PGC
      1alpha.
AB  - Pathological remodeling of the myocardium in chronic heart failure includes the
      development of pathological cardiac hypertrophy, reactivation of the fetal
      genetic program, and disorders in cardiac energy metabolism. Coactivator-1alpha
      of receptor gamma activated by peroxisome proliferator (PGC-1alpha), a
      transcription coactivator of nuclear receptors and metabolism master regulator,
      plays an important role in cardiac metabolism regulation. Studies on the animals
      models of chronic heart failure have demonstrated the development of pathological
      cardiac hypertrophy, metabolic disorders, and reactivation of the fetal genetic
      program; these processes are mutually related. An important role in regulation of
      these processes belongs to PGC-1alpha; its low expression indicates low activity
      and down-regulation of this coactivator. Pathological cardiac hypertrophy,
      decrease of PGC-1alpha activity, and reactivation of the fetal genetic program in
      chronic heart failure are demonstrated.

PMID- 29658072
TI  - Circular RNA: New Regulatory Molecules.
AB  - Circular RNA are a family of covalently closed circular RNA molecules, formed
      from pre-mRNA of coding genes by means of splicing (canonical and alternative
      noncanonical splicing). Maturation of circular RNA is regulated by cis- and trans
      elements. Complete list of biological functions of these RNA is not yet compiled;
      however, their capacity to interact with specific microRNA and play a role of a
      depot attracts the greatest interest. This property makes circular RNA active
      regulatory transcription factors. Circular RNA have many advantages over their
      linear analogs: synthesis of these molecules is conservative, they are universal,
      characterized by clearly determined specificity, and are resistant to
      exonucleases. In addition, the level of their expression is often higher than
      that of their linear forms. It should be noted that expression of circular RNA is
      tissue-specific. Moreover, some correlations between changes in the repertoire
      and intensity of expression of circular RNA and the development of some
      pathologies have been detected. Circular RNA have certain advantages and can
      serve as new biomarkers for the diagnosis, prognosis, and evaluation of response
      to therapy.

PMID- 29658073
TI  - Comparative Characteristics of Discrimination of S. enterica Isolates by
      Phagotyping Test and Dienes Test.
AB  - We propose an original methodological approach to discrimination of newly
      isolated Salmonella enterica strains with the use of Dienes test. Dienes test is
      used for identification of P. vulgaris and P. mirabilis strains. It consists in
      growth suppression by mobile bacterial strain cultures and the formation of a
      demarcation line (Dienes line) between the strains growing towards each other.
      Similarities and differences between salmonella phagotyping method and Dienes
      test-based discrimination of the strains are detected. The studied sample of
      salmonellas was divided into 12 phagotypes. Cluster analysis has shown that most
      of the salmonella strains could not be clusterized by both methods.
      Discrimination by different methods has shown that the largest clusters contain
      the same strains. Clusterization of salmonella strains by different methods shows
      moderate congruency. Rand index used for comparison of the results of the sample
      clusterization by different methods is 0.88. High heterogeneity of salmonella
      strains is presumably explained by heterogeneity of antagonism factors within the
      S. enterica species. Intraspecies antagonism is essential for limitation of the
      horizontal gene transfer in closely related strains and for increase of the
      genetic heterogeneity of salmonella population in the host.

PMID- 29658074
TI  - Injection of Multipotent Mesenchymal Stromal Cells as a Cause of Hemorrhages in
      the Regional Lymph Nodes: Experimental Study.
AB  - Hemorrhagic changes after subcutaneous injection of autologous bone marrow
      multipotent mesenchymal cells with transfected GFP gene and additionally stained
      cell membranes to WAG rats in the projection of ligated femoral vein were studied
      by fluorescent microscopy. Hemorrhages in tissues with experimental acute local
      venous occlusion were caused by a combination of venous hypertension with
      inflammation around the foreign body - the ligature used for ligation of the
      vein. Fibrin found in tissues together with erythrocytes in the hemorrhages could
      stimulate the formation of granulations and new vessels instead of damaged or
      thrombosed ones. Multipotent mesenchymal stromal cells and their detritus getting
      into the regional lymph nodes initiated immune reactions morphologically
      confirmed by stubborn hypertrophy and hyperplasia of the lymphoid nodules,
      hemorrhages, and manifest diapedesis of erythrocytes to the organ parenchyma and
      sinus system.

PMID- 29658075
TI  - Induced Pluripotent Stem Cell-Derived Hematopoietic Embryoid Bodies Secrete
      Sphingosine-1-Phosphate and Revert Endothelial Injury.
AB  - The possibility of sphingosine-1-phosphate production by induced pluripotent stem
      cells is examined to assess their potential in treatment of sepsis. The
      hematopoietic embryoid bodies were derived from the culture of 6-day-old
      differentiated induced pluripotent stem cells. These embryoid bodies secreted
      sphingosine-1-phosphate, an important bioactive lipid that regulates integrity of
      the pulmonary endothelial barrier, prevents elevation of its permeability, and
      impedes the formation of stress fibers in human endotheliocytes derived from
      umbilical vein. The data attest to potentiality of induced pluripotent stem cells
      in treatment of sepsis.

PMID- 29658076
TI  - Expression of Bcl-2 Family Proteins in the Ovarian Follicular Apparatus in the
      Acute Period after Experimental Hyperthermia.
AB  - The expression of apoptosis regulators (proapoptotic protein Bad and anti
      apoptotic protein Bcl-2) was analyzed and Bcl-2/Bad ratio in the follicular
      apparatus of the rat ovary was determined on day 3 after hyperthermia (rectal
      temperature 43.5 degrees C). Hyperthermia in the catabolic phase leads to
      different degrees of activation of the molecular "switches" of apoptosis in cells
      of ovarian follicular epithelium. This was seen from increased intensity of
      immunohistochemical staining for Bad protein against the background of more
      pronounced expression of Bcl-2 protein. On day 3 after exposure to hyperthermia,
      Bcl-2/Bad ratio increased, which reflects antiapoptotic protection of cells and
      conditions for blockade of mitochondrial pathway of apoptosis in the follicular
      apparatus of the ovaries during the acute period after hyperthermia.

PMID- 29658077
TI  - In Vivo Experimental Study of Biological Compatibility of Tissue Engineered
      Tracheal Construct in Laboratory Primates.
AB  - Biological compatibility of a tissue engineered construct of the trachea
      (synthetic scaffold) and allogenic mesenchymal stem cells was studied on
      laboratory Papio hamadryas primates. Subcutaneous implantation and orthotopic
      transplantations of tissue engineered constructs were carried out. Histological
      studies of the construct showed chaotically located filaments and mononuclear
      cells fixed to them. Development of a fine connective tissue capsule was found at
      the site of subcutaneous implantation of the tissue engineered construct. The
      intact structure of the scaffold populated by various cell types in orthotopic
      specimens was confirmed by expression of specific proteins. The results indicated
      biological compatibility of the tissue engineered construct with the mesenchymal
      stem cells; no tissue rejection reactions were recorded; simulation of
      respiratory disease therapy on Papio hamadryas proved to be an adequate model.

PMID- 29658078
TI  - Analysis of the Role of Carriership of Polymorphic Genotypes of ESR1, eNOS, and
      APOE4 Genes in the Development of Arterial Hypertension in Men.
AB  - We studied the role of the carrier status for polymorphic loci of genes encoding
      estrogen receptors (ESR1), endothelial NO synthase (eNOS), and apolipoprotein E
      (APOE4) and products of their expression nitrogen oxide (NO) and apolipoprotein
      (ApoE) in the development of arterial hypertension in men. Conventionally healthy
      volunteers and 149 men with clinical manifestations of stage I-II arterial
      hypertension were examined. In men with arterial hypertension, the frequency of
      minor allele A of ESR1 gene was higher (27.5 vs. 9.5% in the reference group;
      chi2=4.43, p=0.04). The level of NO in the peripheral blood was also higher in
      the main group (chi2=3.93, p=0.047). The increase in NO concentration did not
      depend on the presence of polymorphic genotypes (GG and GT) of eNOS gene, but the
      decrease in ApoE level in blood serum was associated with TC genotype of APOE4
      gene (p=0.04). Our results suggest that minor allele A of ESR1 gene is associated
      with the development of arterial hypertension in men. Reduced content of ApoE in
      blood serum of men with arterial hypertension was associated with APOE4 gene
      polymorphism. However, increased level of NO did not depend on polymorphic
      genotypes GG and GT of eNOS gene. These polymorphisms are of specific interest as
      additional markers of genetic predisposition to the development of arterial
      hypertension in middle-age men.

PMID- 29658079
TI  - TNFalpha-Induced Expression of Transport Protein Genes in HUVEC Cells Is
      Associated with Enhanced Expression of Transcription Factor Genes RELB and NFKB2
      of the Non-Canonical NF-kappaB Pathway.
AB  - Endothelial HUVEC cells used as an in vitro model of the endothelial monolayer in
      placental barrier were activated by TNFalpha in a dose of 2 ng/ml for 24 h.
      Significant changes in the expression of genes of the SLC family transport
      protein were observed: an increase in the expression of SLC7A2, SLC12A2, SLC9B2,
      SLC25A37, SLC16A9, and SLC41A2 and a decrease in the expression of SLC40A1. These
      transporters participate in the transport of iron, magnesium, sodium, potassium,
      and chloride ions, protons, and amino acids. It was also found that SLC7A2,
      SLC12A2, SLC9B2, SLC25A37, and SLC41A2 genes have binding sites for
      transcriptional factor RelB that together with NFKB2 is the main effector of the
      non-canonical NF-kappaB pathway. The expression of RELB and NFKB2 genes was also
      significantly enhanced in TNFalpha-activated HUVEC cells, which can attest to the
      important role of the non-canonical NF-kappaB pathway in the regulation of gene
      expression of transport proteins in response to TNFalpha stimulation.

PMID- 29658080
TI  - Effect of Nanocrystalline Particles of Chitin on Blood Components in Humans and
      Experimental Animals.
AB  - Nanocrystalline particles of chitin in the form of hydrosol in a concentration of
      0.63 mg/ml have no effect on aggregation of human platelets and clotting time of
      platelet-poor plasma in coagulation tests. ADP-induced aggregation of human
      platelets was inhibited by these nanoparticles in concentrations of 0.63 and 1.00
      mg/ml in comparison with the control. Intravenous administration of nanoparticles
      in a dose of 1 mg/kg to guinea pigs produced no anticoagulant effect. The
      nanocrystalline particles of chitin can be of interest as potential drug delivery
      systems.

PMID- 29658081
TI  - Changes in Activity of Matrix Metalloproteinases and Serum Concentrations of
      Proinsulin and C-Peptide Depending on the Compensation Stage of Type 2 Diabetes
      Mellitus.
AB  - In patients with type 2 diabetes mellitus, serum activities of MMP-2 and MMP-7
      were substantially decreased in comparison with apparently healthy individuals.
      At the decompensation stage, along with the increased content of glucose and
      glycated hemoglobin, a pronounced (3-fold) increase in proinsulin concentration
      was observed. On the contrary, MMP activity and C-peptide concentration decreased
      at this stage. The ratio of proinsulin concentration to MMP activity at the
      stages of diabetes mellitus compensation and subcompensation was approximately
      1:50, while at the stage of decompensation it was 1:12. Thus, the ratio of these
      blood serum parameters can be used as an additional diagnostic marker of diabetes
      decompensation and severity of its complications.

PMID- 29658082
TI  - Effect of Oxidized Dextran on Cytokine Production and Activation of IRF3
      Transcription Factor in Macrophages from Mice of Opposite Strains with Different
      Sensitivity to Tuberculosis Infection.
AB  - We studied differences in the production of pro- and anti-inflammatory cytokines
      and IRF3 transcription factor by peritoneal macrophages from mice of opposite
      strains CBA/J and C57Bl/6 and the effect of 60-kDa oxidized dextran on these
      parameters. Macrophages from C57Bl/6 mice were mainly characterized by the
      production of proinflammatory cytokines TNFalpha, IL-12, and MCP-1 (markers of M1
      polarization). By contrast, CBA/J mice exhibited a relatively high level of anti
      inflammatory cytokine IL-10 and lower expression of proinflammatory cytokines (M2
      phenotype). IRF3 content in peritoneal macrophages of CBA/J mice was higher than
      in C57Bl/6 mice. Oxidized dextran decreased the expression of IRF3 upon
      stimulation of cells from CBA/J mice with LPS, but increased this process in
      C57Bl/6 mice. Despite a diversity of oxidized dextran-induced changes in cytokine
      production, the data confirm our hypothesis that this agent can stimulate the
      alternative activation of macrophages.

PMID- 29658083
TI  - Antidiabetic Properties of Low-Molecular-Weight BDNF Mimetics Depend on the Type
      of Activation of Post-Receptor Signaling Pathways.
AB  - Reduced proliferation and enhanced apoptosis of beta cells in diabetes mellitus
      are associated with a deficiency of brain-derived neurotrophic factor (BDNF). Low
      molecular weight compounds similar to different BDNF loops were synthesized at
      the V. V. Zakusov Research Institute of Pharmacology. They produce a potentiating
      effect on TrkB phosphorylation, but differently activate post-receptor signaling
      pathways. We compared their effects on the severity of streptozotocin-induced
      diabetes mellitus in C57Bl/6 mice. The antidiabetic effect (estimated from the
      degree of hyperglycemia and dynamics of body weight) was typical of GSB-214
      compound that selectively activates PI3K/Akt. This activity was not revealed in
      GTS-201, selective activator of MAPK/Erk. GSB-106 compound activating both
      signaling pathways exhibited weak antidiabetic activity. Our results indicate
      that the antidiabetic effect is mainly related to activation of the PI3K/Akt
      signaling pathway.

PMID- 29658084
TI  - Modeling of 3D Structure of Chimeric Constructs Based on Hemagglutinin of
      Influenza Virus and Immunogenic Epitopes of Streptococcus Agalactiae.
AB  - A project of an experimental recombinant vector vaccine for prevention of
      diseases caused by pathogenic streptococci based on ScaAB lipoprotein of
      Streptococcus agalactiae and a coldadapted strain of live influenza vaccine as a
      vector was developed. The sequence of ScaAB lipoprotein was analyzed and
      fragments forming immunodominant epitopes were determined. Chimeric molecules of
      influenza virus hemagglutinin H7 carrying insertions of bacterial origin were
      constructed. Based on the results of simulation, the most promising variants were
      selected; they represented fragments of lipoprotein ScaAB lacking N-terminal
      domain bound to hemagglutinin via a flexible linker. These insertions should
      minimally modulate the properties of the influenza strain, while retaining
      potential immunogenicity to a wide group of pathogenic streptococci.

PMID- 29658086
TI  - Coupling of Lipoperoxidation Reactions with Changes in Arterial Blood Pressure in
      Hypertensive ISIAH Rats under Conditions of Chronic Stress.
AB  - Mature normotensive male WAG rats and stress-sensitive hypertensive ISIAH rats
      were exposed to "everyday life stress" modelled by alternation of immobilization
      and adaptation. Increased LPO intensity (increased content of substrates with
      unsaturated double bonds and primary and secondary LPO products) and reduced
      content of some antioxidant protection components (reduced retinol level and
      GSH/GSSG ratio) were revealed in the blood of ISIAH rats. These changes
      correlated with elevated mean BP. The results can reflect the significant role of
      LPO changes in the pathogenesis of stress-induced arterial hypertension.

PMID- 29658085
TI  - Effect of Natural Cytokine Complex on the Structure and Metabolism of the Cardiac
      Conduction System in the Myocardium under Normally and Increased Hemodynamic
      Load.
AB  - Effect of natural complex of cytokines with activity of IL-1, IL-2, IL-6, TNF,
      MIF, and GTFbeta on the structure and metabolism of conduction cardiomyocytes was
      assessed in the control and under acute experimental aortic stenosis. After
      systemic administration of the cytokine complex in the control, structural
      abnormalities were revealed in a relatively low number of conduction
      cardiomyocytes; their relative number increased in the left ventricle and
      interventricular septum. When the complex was administered against the background
      of aortic stenosis, morphological changes in the conduction system were seen in a
      significant number of cells with their plasma imbibition, especially in the left
      ventricle and interventricular septum. Systemic administration of the natural
      cytokine complex inhibited the major metabolic processes in the conduction
      system, both in the control and under conditions of sharply increased hemodynamic
      load. In conduction cardiomyocytes, deceleration of glycolysis and citric acid
      cycle, inhibition of oxidation of free fatty acids and their metabolites, and
      suppression of shuttle mechanisms and biosynthetic reactions were observed.
      Increased blood levels of cytokines, primarily of the proinflammatory ones, can
      cause structural and metabolic disturbances in the cardiac conduction system and
      promote the development of arrhythmias, especially in case of sharply increased
      hemodynamic load.

PMID- 29658087
TI  - Complex Analysis of Total and Fetal DNA and Cytokines in Blood Plasma of Pregnant
      Women with Preeclampsia.
AB  - We performed a complex analysis of total and fetal extracellular DNA, 8 cytokines
      (IL-2, IL-4, IL-6, IL-8, IL-10, granulocyte-macrophage CSF, IFNgamma, and
      TNFalpha) in blood plasma obtained from women with preeclampsia prior to labor
      onset. Total (sensitivity 89.47%, specificity 93.75%) and fetal extracellular DNA
      (sensitivity 73.68%, specificity 87.5%) were the most accurate parameters
      determining preeclampsia. We revealed a high correlation (p=3*10-6) between total
      and fetal extracellular DNA levels in the group of preeclampsia. Preeclampsia
      significantly increased the levels of macrophage factors IL-10 and IL-6. These
      cytokines significantly correlated with the levels of total and fetal
      extracellular DNA in the preeclampsia group. In the control group, such
      correlations were not observed. These findings obtained suggest that preeclampsia
      develops upon increased macrophage activity, leading to destruction of the
      placenta trophoblast cells.

PMID- 29658088
TI  - Pathogenetic Role of Endothelial Dysfunction in Idiopathic Vestibulopathy.
AB  - Comparative analysis of the groups of patients with idiopathic bilateral
      vestibular hypofunction and a group of vestibulopathy patients with
      vertebrobasilar insufficiency demonstrated identity of the basic and additional
      diagnostic parameters in these syndromes as well as similarity in clinical
      diagnostic and anamnesis data. In all cases, functional assessment of endothelium
      dependent vasodilation and selected biochemical marker sICAM-1 revealed
      endothelial dysfunction. Drug correction of endothelial dysfunction positively
      affected the manifestations of major and minor features of the syndrome, which
      confirmed the contribution of endothelial functional disturbances to the
      pathogenesis of bilateral vestibular hypofunction.

PMID- 29658089
TI  - Electrophysiological Properties of Rat Vestibular Labyrinth and Their Effect on
      Parameters of Transmitted Voltage Pulses.
AB  - We propose a new approach to optimization of electrical stimulation of the
      vestibular nerve and improving the transfer function of vestibular implant. A
      mathematical model of the vestibular organ is developed based on its anatomy, the
      model premises, 3D-analysis of MRI and CT images, and mathematical description of
      physical processes underlying propagation of alternating electric current across
      the tissues of vestibular labyrinth. This approach was tested in vitro on the rat
      vestibular apparatus and had been examined anatomically prior to the development
      of its mathematical model and equivalent electrical circuit. The experimental and
      theoretical values of changes of the gain-phase characteristics of vestibular
      tissues in relation to location of the reference electrode obtained in this study
      can be used to optimize the electrical stimulation of vestibular nerve.

PMID- 29658090
TI  - Bimodal Electrical Properties of Rat Major Artery Segment In Situ.
AB  - In experiments on narcotized rats, BP in the left femoral artery as well as local
      electrical potential and electrical impedance of the symmetric segment of the
      right femoral artery were simultaneously recorded in situ with two extracellular
      nonpolarizable Ag/AgCl electrodes located along the artery at a distance of 3 mm
      from each other. The pulsatile arterial electrical potentials with amplitude of
      100-200 MUV and duration of about 50 msec were recorded, which coincided with the
      front of BP wave corrected for a 10-msec delay of the pressure transducer. Under
      normal conditions, the pulsatile oscillations of arterial electroimpedance were
      in-phase with BP oscillations, so the rising phase of BP was paralleled by
      elevation of electroimpedance reflecting constriction of the arterial segment.
      This finding is viewed as indicative of periodic myogenic Ostroumov-Bayliss
      effect triggered by arterial pulse. After local application of tetrodotoxin (3*10
      7 M), procaine (0.5%), or lidocaine (spray 10%) to isolated arterial segment, its
      electroimpedance oscillated out-of-phase with BP, so the changes of
      electroimpedance were similar to the response of a passive elastic tube to
      pulsatile BP. The applied agents completely (tetrodotoxin) or pronouncedly
      (procaine, lidocaine) inhibited the pulsatile arterial electrical potential. The
      present data indicate the possibility of passive and active modes of arterial
      pulsing, which differ by the amplitude of pulsatile arterial electrical potential
      as well as by phasic relations between BP and electroimpedance. The possible
      physiological role of various modes of pulsing in major arteries is discussed.

PMID- 29658091
TI  - Improving the evidence base for services working with youth at-risk of
      involvement in the criminal justice system: developing a standardised program
      approach.
AB  - BACKGROUND: Young people who engage in multiple risk behaviour (high-risk young
      people) such as substance abuse, antisocial behaviour, low engagement in
      education and employment, self-harm or suicide ideation are more likely to
      experience serious harms later in life including homelessness, incarceration,
      violence and premature death. In addition to personal disadvantage, these harms
      represent an avoidable social and economic cost to society. Despite these harms,
      there is insufficient evidence about how to improve outcomes for high-risk young
      people. A key reason for this is a lack of standardisation in the way in which
      programs provided by services are defined and evaluated. METHODS: This paper
      describes the development of a standardised intervention model for high-risk
      young people. The model can be used by service providers to achieve greater
      standardisation across their programs, outcomes and outcome measures. To
      demonstrate its feasibility, the model is applied to an existing program for high
      risk young people. CONCLUSIONS: The development and uptake of a standardised
      intervention model for these programs will help to more rapidly develop a larger
      and more rigorous evidence-base to improve outcomes for high-risk young people.

PMID- 29658094
TI  - Modification of polydopamine-coated Fe3O4 nanoparticles with multi-walled carbon
      nanotubes for magnetic-MU-dispersive solid-phase extraction of antiepileptic
      drugs in biological matrices.
AB  - In this study, multi-walled carbon nanotubes were coated on the surface of
      magnetic nanoparticles modified by polydopamine. The synthesized composite was
      characterized and applied to magnetic-MU-dispersive solid-phase extraction of
      oxcarbazepine (OXC), phenytoin (PHT), and carbamazepine (CBZ) from human plasma,
      urine, and cerebrospinal fluid samples prior to analysis by a high-performance
      liquid chromatography-photodiode array detector. The extraction parameters were
      investigated and the optimum condition was obtained when the variables were set
      to the following: sorbent type, Fe3O4@polyDA-MWCNTs (length < 2 MUm); sample pH,
      6; amount of sorbent, 15 mg; sorption time, 1.5 min at room temperature; type and
      volume of the eluent, 2.5 mL methanol; and salt content, none added. Under the
      optimized conditions, the calibration curves are linear in the concentration
      range 2-2000 ng/mL, the limits of detection are in the range 0.4-3.1 ng/mL, and
      the relative standard deviations and relative recoveries of plasma (spiked at 200
      ng/mL) and CSF (spiked at 50 ng/mL) are in the ranges 1.4-8.2% and 92.8-96.5%,
      respectively. The applicability of the method was successfully confirmed by
      extraction and determination of OXC, PHT, and CBZ in biological matrices.
      Graphical abstract Magnetic multi-walled carbon nanotube core-shell composites
      were applied as magnetic-MU-dispersive solid-phase extraction adsorbents for
      determination of antiepileptic drugs in biological matrices.

PMID- 29658093
TI  - Metabolomic study of human tissue and urine in clear cell renal carcinoma by LC
      HRMS and PLS-DA.
AB  - Renal cell carcinoma (RCC) is the most prevalent and lethal malignancy of the
      kidney. Despite all the efforts made, no tissue biomarker is currently used in
      the clinical management of patients with kidney cancer. A search for possible
      biomarkers in urine for clear cell renal cell carcinoma (ccRCC) has been
      conducted. Non-targeted metabolomic analyses were performed on paired samples of
      surgically removed renal cancer and normal tissue, as well as on urine samples.
      Extracts were analyzed by liquid chromatography/high-resolution mass spectrometry
      (LC-HRMS). Hydroxybutyrylcarnitine, decanoylcarnitine, propanoylcarnitine,
      carnitine, dodecanoylcarnitine, and norepinephrine sulfate were found in much
      higher concentrations in both cancer tissues (compared with the paired normal
      tissue) and in urine of cancer patients (compared with control urine). In
      contrast, riboflavin and acetylaspartylglutamate (NAAG) were present at
      significantly higher concentrations both in normal kidney tissue as well as in
      urine samples of healthy persons. This preliminary study resulted in the
      identification of several compounds that may be considered potential clear cell
      renal carcinoma biomarkers. Graphical abstract PLS-DA plot based on LC-MS data
      for normal and cancer human tissue samples. The aim of this work was the
      identification of up- and downregulated compounds that could potentially serve as
      renal cancer biomarkers.

PMID- 29658095
TI  - Compatible above-ground biomass equations and carbon stock estimation for small
      diameter Turkish pine (Pinus brutia Ten.).
AB  - Small trees and saplings are important for forest management, carbon stock
      estimation, ecological modeling, and fire management planning. Turkish pine
      (Pinus brutia Ten.) is a common coniferous species and comprises 25.1% of total
      forest area of Turkey. Turkish pine is also important due to its flammable fuel
      characteristics. In this study, compatible above-ground biomass equations were
      developed to predict needle, branch, stem wood, and above-ground total biomass,
      and carbon stock assessment was also described for Turkish pine which is smaller
      than 8 cm diameter at breast height or shorter than breast height. Compatible
      biomass equations are useful for biomass prediction of small diameter individuals
      of Turkish pine. These equations will also be helpful in determining fire
      behavior characteristics and calculating their carbon stock. Overall, present
      study will be useful for developing ecological models, forest management plans,
      silvicultural plans, and fire management plans.

PMID- 29658096
TI  - Effect of low level laser and low intensity pulsed ultrasound therapy on bone
      remodeling during orthodontic tooth movement in rats.
AB  - BACKGROUND: Quality bone regeneration, which leads to the improvement of bone
      remodeling, is essential for orthodontic treatment. In order to improve bone
      regeneration and increase the amount of tooth movement, different techniques have
      been implemented. The object of this study is to compare the effects of low-level
      laser therapy (LLLT), low-intensity pulsed ultrasound (LIPUS), and their
      combination on bone remodeling during orthodontic tooth movement. METHODS: Eighty
      (80) male, 6-week-old Sprague Dawley rats were grouped in to four groups, the
      first group was irradiated with (940 nm) diode laser, second group with LIPUS,
      and third group with combination of both LLLT and LIPUS. A forth group used was a
      control group in an incomplete block split-mouth design. The LLLT and LIPUS were
      used to treat the area around the moving tooth once a day on days 0-7, then the
      experiment was ended in each experimental endpoint (1, 3, 7, 14, and 21 days).
      For amount of tooth movement, models were imaged and analyzed. Histological
      examination was performed after staining with (hematoxylin and eosin) and
      (alizarin red and Alcian Blue) stain. One step reverse transcription-polymerase
      chain reaction RT-PCR was also performed to elucidate the gene expression of
      RANK, RANKL, OPG, and RUNX-2. RESULTS: The amount of tooth movement, the
      histological bone remodeling, and the RT-PCR were significantly greater in the
      treatment groups than that in the control group. Among the treatment groups, the
      combination group was the highest and the LIPUS group was the lowest. CONCLUSION:
      These findings suggest that LLLT and LIPUS can enhance the velocity of tooth
      movement and improve the quality of bone remodeling during orthodontic tooth
      movement.

PMID- 29658097
TI  - Anesthetized by chloroform before hanging.
AB  - We present a unique case of suicidal hanging. The deceased was a 31-year-old male
      who was found hanging from a tree in a dense thicket, with his lower limbs in
      contact with the ground (partial suspension). There was an apparatus similar to a
      facial mask placed around his nose and mouth. A strong chemical smell was
      emanating from the apparatus, which was identified as chloroform (Formyl
      trichloride/CHCl3). A ligature with a soft cloth beneath it was around his neck.
      A ligature mark was present around the neck. The decedent's blood alcohol levels
      were 112 mg/dl. The blood and stomach contents were negative for chloroform. A
      complete death investigation, including scene investigation and complete autopsy
      examination, confirmed the cause of death as hanging. The manner of death was
      suicide. This case highlights how the deceased had used several methods whilst
      committing suicide to minimize pain, including the inhalation of chloroform,
      which would have also resulted in the inability to engage in protective actions
      during the act.

PMID- 29658098
TI  - Efficacy of a proactive health and safety risk management system in the fire
      service.
AB  - BACKGROUND: This study evaluated the efficacy of a fire department proactive risk
      management program aimed at reducing firefighter injuries and their associated
      costs. METHODS: Injury data were collected for the intervention fire department
      and a contemporary control department. Workers' compensation claim frequency and
      costs were analyzed for the intervention fire department only. Total, exercise,
      patient transport, and fireground operations injury rates were calculated for
      both fire departments. RESULTS: There was a post-intervention average annual
      reduction in injuries (13%), workers' compensation injury claims (30%) and claims
      costs (21%). Median monthly injury rates comparing the post-intervention to the
      pre-intervention period did not show statistically significant changes in either
      the intervention or control fire department. CONCLUSIONS: Reduced workers'
      compensation claims and costs were observed following the risk management
      intervention, but changes in injury rates were not statistically significant.

PMID- 29658099
TI  - Identification of serotoninergic system components in stallion sperm.
AB  - Assisted reproductive techniques have been used on several domestic animals to
      preserve desirable traits in strains of high genetic and commercial value;
      however in equines its efficiency rate is relatively low. To increase the
      conception ratio in stallions, some research groups have used pharmacological
      treatments which promote sperm hyperactivation in order to increase male's
      fertility rates. In this way, our previous work suggests that serotonin (5-HT)
      could be a good pharmacological candidate that facilitates conception rate in
      domestic horses. 5-HT is a neurohormone involved in several reproductive
      processes, i.e., it enhances hyperactivation, motility, and promotes the acrosome
      reaction in mammalian sperm, but it has not been described in the stallion sperm
      yet. Therefore, using both immunofluorescence and western blot techniques, we
      searched for and found some serotonin markers such as 5-HT, 5-HT1B, 5-HT2A, 5-HT3
      receptors, both TPH1 and MAOA enzymes, and serotonin transporter (5-HTT) in
      stallion sperm. In addition, we found a non-neuroendocrine cell, V-MAT1
      transporter, which has not been previously reported in mammalian sperm. Our
      results suggest that serotoninergic system is present in stallion sperm, which
      could be a pharmacological target to increase the conception rates in domestic
      horses.

PMID- 29658100
TI  - Excess iron stress reduces root tip zone growth through nitric oxide-mediated
      repression of potassium homeostasis in Arabidopsis.
AB  - The root tip zone is regarded as the principal action site for iron (Fe) toxicity
      and is more sensitive than other root zones, but the mechanism underpinning this
      remains largely unknown. We explored the mechanism underpinning the higher
      sensitivity at the Arabidopsis root tip and elucidated the role of nitric oxide
      (NO) using NO-related mutants and pharmacological methods. Higher Fe sensitivity
      of the root tip is associated with reduced potassium (K+ ) retention. NO in root
      tips is increased significantly above levels elsewhere in the root and is
      involved in the arrest of primary root tip zone growth under excess Fe, at least
      in part related to NO-induced K+ loss via SNO1 (sensitive to nitric oxide 1)/SOS4
      (salt overly sensitive 4) and reduced root tip zone cell viability. Moreover,
      ethylene can antagonize excess Fe-inhibited root growth and K+ efflux, in part by
      the control of root tip NO levels. We conclude that excess Fe attenuates root
      growth by effecting an increase in root tip zone NO, and that this attenuation is
      related to NO-mediated alterations in K+ homeostasis, partly via SNO1/SOS4.

PMID- 29658101
TI  - Abstracts of the 58th Annual Scientific Meeting of the British Society for
      Haematology, 16-18 April 2018, Liverpool, UK.

PMID- 29658102
TI  - Earfold: A New Technique for Correction of the Shape of the Antihelix.
AB  - An absent or poorly defined antihelix often plays a central role in the
      perception of the prominent ear. A wide variety of otoplasty techniques have been
      described over the last 50 years that aim to reshape, create, or enhance the
      definition of the antihelix, which can, in turn, help to reduce the prominence of
      an ear. In addition to conventional suture and cartilage-scoring techniques, a
      permanent implantable clip system (Earfold(r) ) has recently become available
      that is placed using a minimally invasive approach performed under local
      anesthesia. In this review, we summarize conventional otoplasty techniques to
      correct the antihelix and compare these with the Earfold implantable clip system.
      Laryngoscope, 128:2282-2290, 2018.

PMID- 29658104
TI  - Comparison of the seventh and eighth edition american joint committee on cancer
      oral cavity staging systems.
AB  - OBJECTIVE: For the first time in 30 years, the eighth edition of the American
      Joint Committee on Cancer (AJCC) Staging Manual offers major changes in the
      staging of oral cavity cancer. We evaluated the predictive ability of the new
      staging system for oral cavity cancer to validate these changes and hypothesized
      that the new system would improve prognostic accuracy. METHODS: We conducted a
      retrospective cohort study of patients with oral cavity squamous cell carcinoma
      in the National Cancer Data Base from 2009 to 2013 and applied the seventh and
      eighth edition staging AJCC staging systems to all patients. Stage-specific
      overall survival was calculated using the Kaplan-Meier method and concordance
      indices to measure the system's prognostic accuracy. RESULTS: We identified
      39,361 patients with a median follow-up of 27.1 months (range 0.1-80.4 months).
      In the seventh edition, there were 43.0%, 15.0%, 10.6%, and 25.7% of patients
      with pathologic stage I, II, III, and IV disease, respectively. After restaging
      based on eighth edition pathological guidelines, 10.0% of patients were upstaged
      (38.1%, 18.1%, 14.2%, and 25.2%, respectively, with stage I, II, III, and IV
      disease, respectively). The survival concordance index improved from the seventh
      to eighth edition for pathological staging (concordance index 0.699 and 0.704,
      respectively) and for clinical staging (concordance index 0.714 and 0.715,
      respectively). CONCLUSION: We provide validation of the new AJCC staging system
      for oral cavity cancer. Eighth edition AJCC staging guidelines upstage a
      substantial number of patients with greater depth of invasion or extranodal
      extension. This resulted in slightly improved prognostication. LEVEL OF EVIDENCE:
      2c. Laryngoscope, 128:2351-2360, 2018.

PMID- 29658103
TI  - Genioglossus reflex responses to negative upper airway pressure are altered in
      people with tetraplegia and obstructive sleep apnoea.
AB  - KEY POINTS: Protective reflexes in the throat area (upper airway) are crucial for
      breathing. Impairment of these reflexes can cause breathing problems during sleep
      such as obstructive sleep apnoea (OSA). OSA is very common in people with spinal
      cord injury for unknown reasons. This study shows major changes in protective
      reflexes that serve to keep the upper airway open in response to suction
      pressures in people with tetraplegia and OSA. These results help us understand
      why OSA is so common in people with tetraplegia and provide new insight into how
      protective upper airway reflexes work more broadly. ABSTRACT: More than 60% of
      people with tetraplegia have obstructive sleep apnoea (OSA). However, the
      specific causes are unknown. Genioglossus, the largest upper-airway dilator
      muscle, is important in maintaining upper-airway patency. Impaired genioglossus
      muscle function following spinal cord injury may contribute to OSA. This study
      aimed to determine if genioglossus reflex responses to negative upper-airway
      pressure are altered in people with OSA and tetraplegia compared to non
      neurologically impaired able-bodied individuals with OSA. Genioglossus reflex
      responses measured via intramuscular electrodes to ~60 brief (250 ms) pulses of
      negative upper-airway pressure (~-15 cmH2 O at the mask) were compared between 13
      participants (2 females) with tetraplegia plus OSA and 9 able-bodied controls (2
      females) matched for age and OSA severity. The initial short-latency excitatory
      reflex response was absent in 6/13 people with tetraplegia and 1/9 controls.
      Genioglossus reflex inhibition in the absence of excitation was observed in three
      people with tetraplegia and none of the controls. When the excitatory response
      was present, it was significantly delayed in the tetraplegia group compared to
      able-bodied controls: excitation onset latency (mean +/- SD) was 32 +/- 16 vs. 18
      +/- 9 ms, P = 0.045; peak excitation latency was 48 +/- 17 vs. 33 +/- 8 ms, P =
      0.038. However, when present, amplitude of the excitation response was not
      different between groups, 195 +/- 26 vs. 219 +/- 98% at baseline, P = 0.55. There
      are major differences in genioglossus reflex morphology and timing in response to
      rapid changes in airway pressure in people with tetraplegia and OSA. Altered
      genioglossus function may contribute to the increased risk of OSA in people with
      tetraplegia. The precise mechanisms mediating these differences are unknown.

PMID- 29658105
TI  - The impact of domestication and crop improvement on arbuscular mycorrhizal
      symbiosis in cereals: insights from genetics and genomics.
AB  - Contents Summary 1135 I. Introduction 1135 II. Recruitment of plant metabolites
      and hormones as signals in AM symbiosis 1136 III. Phytohormones are regulators of
      AM symbiosis and targets of plant breeding 1137 IV. Variation in host response to
      AM symbiosis 1137 V. Outlook 1137 Acknowledgements 1139 References 1139 SUMMARY:
      Cereals (rice, maize, wheat, sorghum and the millets) provide over 50% of the
      world's caloric intake, a value that rises to > 80% in developing countries.
      Since domestication, cereals have been under artificial selection, largely
      directed towards higher yield. Throughout this process, cereals have maintained
      their capacity to interact with arbuscular mycorrhizal (AM) fungi, beneficial
      symbionts that associate with the roots of most terrestrial plants. It has been
      hypothesized that the shift from the wild to cultivation, and above all the last
      c. 50 years of intensive breeding for high-input farming systems, has reduced the
      capacity of the major cereal crops to gain full benefit from AM interactions.
      Recent studies have shed further light on the molecular basis of establishment
      and functioning of AM symbiosis in cereals, providing insight into where the
      breeding process might have had an impact. Classic phytohormones, targets of
      artificial selection during the generation of Green Revolution semi-dwarf
      varieties, have emerged as important regulators of AM symbiosis. Although there
      is still much to be learnt about the mechanistic basis of variation in symbiotic
      outcome, these advances are providing an insight into the role of arbuscular
      mycorrhiza in agronomic systems.

PMID- 29658106
TI  - Acute sialadenitis associated with 2017-2018 influenza A infection: A case
      series.
AB  - The influenza A virus has accounted for the majority of influenza infections in
      the 2017 to 2018 flu season, with the typical clinical presentation including
      fever, myalgias, malaise, and nonproductive cough. Notably this season, we have
      recognized a cluster of influenza A cases presenting as severe neck and facial
      swelling, with the subsequent diagnosis of sialadenitis. Whereas previous authors
      have demonstrated isolated case reports of sialadenitis associated with influenza
      A infection, herein we describe the clinical history, laboratory values, and
      radiographic findings of four patients presenting to our institution in January
      2018 with acute sialadenitis and influenza A infection. Laryngoscope, 2500-2502,
      2018.

PMID- 29658107
TI  - Malleostapedotomy in stapes revision surgery: Is an endoscopic approach possible?
AB  - OBJECTIVES/HYPOTHESIS: The purpose of the present study was to show our
      preliminary results regarding the endoscopic ear surgery application in
      malleostapedotomy surgery. STUDY DESIGN: Case series. METHODS: Six patients (four
      females and two males) who underwent endoscopic ear surgery as revision surgery
      for otosclerosis were enrolled in this study. For endoscopic malleostapedotomy
      surgery, rigid angled endoscopes at 0  degrees  and 30  degrees  with a length of
      14 cm and an outer diameter of 3 and 4 mm were used. A superelastic nitinol
      stapes prosthesis was used to connect the malleus neck to the oval window.
      RESULTS: During endoscopic ear surgery, a lateral ossicular chain fixation was
      present in all cases. The mean operative time in the study group was 81 minutes
      (range, 73-89 minutes). A statistically significant difference between
      preoperative and postoperative hearing findings was observed (P = .007). No cases
      of sensorineural hearing loss or persistent vertigo were observed in the study
      sample. No cases of prosthesis displacement or prosthesis extrusion occurred
      after a mean follow-up of 11.5 months. CONCLUSIONS: In 100% of treated cases, the
      endoscope proved to be adequate for the visualization of the malleus handle and
      incus, and of their possible abnormalities. Despite the difficulty related to
      endoscopic single-handed work, none of the surgical steps of endoscopic
      malleostapedotomy were considered not feasible by endoscopic ear surgery. LEVEL
      OF EVIDENCE: 4. Laryngoscope, 2611-2614, 2018.

PMID- 29658108
TI  - Maternal residential pesticide use and risk of childhood leukemia in Costa Rica.
AB  - Evidence suggests that early-life exposure to pesticides inside the home may be
      associated with childhood leukemia, however data from Latin American countries
      are limited. We examined whether self-reported maternal residential pesticide use
      and nearby pesticide applications-before and after child's birth-were associated
      with acute lymphoblastic leukemia (ALL) in the Costa Rican Childhood Leukemia
      Study (CRCLS), a population-based case-control study (2001-2003). Cases (n = 251
      ALL) were diagnosed between 1995 and 2000 (age <15 years at diagnosis) and were
      identified through the Costa Rican Cancer Registry and National Children's
      Hospital. Population controls (n = 577) were drawn from the National Birth
      Registry. We fitted unconditional logistic regression models adjusted for child
      sex, birth year, and socioeconomic status to estimate the exposure-outcome
      associations and also stratified by child sex. We observed that self-reported
      maternal insecticide use inside the home in the year before pregnancy, during
      pregnancy, and while breastfeeding was associated with increased odds of ALL
      among boys [adjusted Odds Ratio (aOR) = 1.63 (95% confidence interval [95% CI]:
      1.05-2.53), 1.75 (1.13-2.73), and 1.75 (1.12-2.73), respectively. We also found
      evidence of exposure-response relationships between more frequent maternal
      insecticide use inside the home and increased odds of ALL among boys and girls
      combined. Maternal report of pesticide applications on farms or companies near
      the home during pregnancy and at any time period were also associated with ALL.
      Our study in Costa Rica highlights the need for education to minimize pesticide
      exposures inside and around the home, particularly during pregnancy and
      breastfeeding.

PMID- 29658109
TI  - PGE2 /EP4 antagonism enhances tumor chemosensitivity by inducing extracellular
      vesicle-mediated clearance of cancer stem cells.
AB  - Cells expressing mesenchymal/basal phenotypes in tumors have been associated with
      stem cell properties. Cancer stem cells (CSCs) are often resistant to
      conventional chemotherapy. We explored overcoming mesenchymal CSC resistance to
      chemotherapeutic agents. Our goal was to reduce CSC numbers in vivo, in
      conjunction with chemotherapy, to reduce tumor burden. Analysis of clinical
      samples demonstrated that COX-2/PGE2 /EP4 signaling is elevated in basal-like and
      chemoresistant breast carcinoma and is correlated with survival and relapse of
      breast cancer. EP4 antagonism elicts a striking shift of breast cancer cells from
      a mesenchymal/CSC state to a more epithelial non-CSC state. The transition was
      mediated by EP4 antagonist-induced extracellular vesicles [(EVs)/exosomes] which
      removed CSC markers, mesenchymal markers, integrins, and drug efflux transporters
      from the CSCs. In addition, EP4 antagonism-induced CSC EVs/exosomes can convert
      tumor epithelial/non-CSCs to mesenchymal/CSCs able to give rise to tumors and to
      promote tumor cell dissemination. Because of its ability to induce a CSC-to-non
      CSC transition, EP4 antagonist treatment in vivo reduced the numbers of CSCs
      within tumors and increased tumor chemosensitivity. EP4 antagonist treatment
      enhances tumor response to chemotherapy by reducing the numbers of chemotherapy
      resistant CSCs available to repopulate the tumor. EP4 antagonism can collaborate
      with conventional chemotherapy to reduce tumor burden.

PMID- 29658110
TI  - Prenatal diethylstilbestrol exposure and mammographic density.
AB  - In a prospective cohort study of the health effects associated with prenatal
      Diethylstilbestrol (DES) exposure, DES was associated with an increased breast
      cancer risk after 40 years of age. It is unknown whether it is associated with
      greater mammographic density, which strongly predicts breast cancer risk. A
      cohort of DES-exposed and unexposed women was assembled at the Mayo Clinic in
      1975, and followed through 2012 as part of the National Cancer Institute's DES
      follow-up study. Mammographic density from 3,637 mammograms for 332 (222 DES
      exposed, 110 unexposed) women in this cohort screened at the Mayo Clinic,
      Rochester between 1996 and 2015 was determined clinically using the Breast
      Imaging Reporting and Data System (BI-RADS). Any effect of prenatal DES exposure
      on mammographic density was estimated using repeated measures logistic
      regression. There was no association between prenatal DES exposure and high
      mammographic density for either premenopausal [Odds ratios (OR) = 0.92 (95%
      Confidence Interval (CI): 0.50, 1.7] or postmenopausal women (OR = 0.90; 95% CI:
      0.54, 1.5). Among premenopausal women, associations differed by body mass index
      (BMI), with ORs of 1.47 (0.70, 3.1) for women with BMI above the median and 0.53
      (0.23, 1.3) for those with BMI below the median (pinteraction  = 0.05). Overall,
      however, prenatal DES exposure was not associated with high mammographic density
      in this sample of DES Study participants. Consequently, this study does not
      provide evidence that high mammographic density is involved with the influence of
      DES on breast cancer risk.

PMID- 29658112
TI  - The influential factors on the morphological changes of upper airway associated
      with mouth opening.
AB  - OBJECTIVE: This study aimed to evaluate the influential factors on the
      morphological changes of upper airway caused by mouth opening (MO). METHODS: One
      hundred and thirty-eight obstructive sleep apnea-hypopnea syndrome (OSAHS)
      patients were enrolled. Anthropometric and demographic data, Friedman tongue
      position (FTP), and tonsil scores were recorded. Overnight polysomnography and
      upper airway computed tomography scans under two conditions (mouth closed [MC]
      and MO) were acquired. Morphological parameters of upper airway were compared
      between MC and MO. Stepwise multiple linear regression analyses were performed
      with the variation ratio of upper airway parameters (Para-VRs) from MC to MO as
      the dependent variable, with age, gender, body mass index, neck circumference,
      waist circumference, four mandibular indexes, net angle or amount of MO, FTP, and
      tonsil scores as the independent variables. RESULTS: Overall analysis and
      subgroup analyses based on OSAHS severity revealed that the minimal cross
      sectional area of oropharyngeal lumen (OXmin) significantly decreased (P < 0.05)
      with MO, whereas the minimal cross-sectional area of velopharyngeal lumen (VXmin)
      did not significantly change with MO (P > 0.05). The net angle of MO or amount of
      MO combined with tonsil scores were identified to have significant positive
      correlation with EXP (OXmin-VR), [OXmin-VR was logarithmically transformed with
      an exponential function, EXP(n) = en ]; FTP appeared to be more related to EXP
      (VXmin-VR). Mouth opening induced a significant increase VXmin for patient
      subgroup with FTP grading I and a significant decrease VXmin for patient subgroup
      with FTP grading IV (P < 0.05). CONCLUSION: Wider MO combined with larger tonsils
      lead to narrower oropharyngeal airway. The relative position of tongue to soft
      palate is the main factor influencing the changes of velopharyngeal lumen with
      MO. LEVEL OF EVIDENCE: IV. Laryngoscope, 2018.

PMID- 29658113
TI  - Has the management of pediatric mucoepidermoid carcinoma of the parotid gland
      changed?
AB  - OBJECTIVES/HYPOTHESIS: To examine the evolving changes in management of pediatric
      mucoepidermoid carcinoma of the parotid gland. STUDY DESIGN: Retrospective
      analysis of a large population database. METHODS: Pediatric patients in the
      Surveillance, Epidemiology, and End Results database were included from 1973 to
      2014 based on a diagnosis of mucoepidermoid carcinoma of the parotid gland using
      the International Classification of Diseases for Oncology, Third Edition codes:
      C07.9: parotid gland and 8430/3: mucoepidermoid carcinoma. Patients were included
      from ages 0 to 18 years. Patients were categorized into 5- or 6-year cohorts
      based on their year of diagnosis. Two-year and 5-year survival was calculated
      using actuarial or life-table analysis. RESULTS: One hundred sixty-nine pediatric
      cases were identified. Eighty of the 169 cases (47.4%) were diagnosed from 2005
      to 2014. The number of cases increased steadily across cohorts over time since
      1995. Pediatric patients tended to be diagnosed in adolescence (mean age: 13.4
      years, range: 3.0-18.0 years). Most patients received surgical management as a
      part of their case (95.3% of total cohort). The 5-year disease-specific survival
      was > 90% for each cohort. CONCLUSIONS: The age-adjusted incidence rate of
      pediatric mucoepidermoid carcinoma of the parotid gland remains low and is not
      greatly changing. This cancer is most likely diagnosed in adolescence affecting
      both male and female patients equally. Analysis of cases since 1973 revealed that
      most patients continue to receive surgical care. Survival for these pediatric
      patients continues to remain excellent. Healthcare providers should note these
      updates in pediatric mucoepidermoid carcinoma of the parotid gland as effective
      diagnosis and management continues to lead to good survival outcomes. LEVEL OF
      EVIDENCE: 4 Laryngoscope, 128:2408-2414, 2018.

PMID- 29658111
TI  - Architectonic characteristics of the visual thalamus and superior colliculus in
      titi monkeys.
AB  - Titi monkeys are arboreal, diurnal New World monkeys whose ancestors were the
      first surviving branch of the New World radiation. In the current study, we use
      cytoarchitectonic and immunohistochemical characteristics to compare titi monkey
      subcortical structures associated with visual processing with those of other well
      studied primates. Our goal was to appreciate features that are similar across all
      New World monkeys, and primates in general, versus those features that are unique
      to titi monkeys and other primate taxa. We examined tissue stained for Nissl
      substance, cytochrome oxidase (CO), acetylcholinesterase (AChE), calbindin (Cb),
      parvalbumin (Pv), and vesicular glutamate transporter 2 (VGLUT2) to characterize
      the superior colliculus, lateral geniculate nucleus, and visual pulvinar. This is
      the first study to characterize VGLUT2 in multiple subcortical structures of any
      New World monkey. Our results from tissue processed for VGLUT2, in combination
      with other histological stains, revealed distinct features of subcortical
      structures that are similar to other primates, but also some features that are
      slightly modified compared to other New World monkeys and other primates. These
      included subdivisions of the inferior pulvinar, sublamina within the stratum
      griseum superficiale (SGS) of the superior colliculus, and specific koniocellular
      layers within the lateral geniculate nucleus. Compared to other New World
      primates, many features of the subcortical structures that we examined in titi
      monkeys were most similar to those in owl monkeys and marmosets, with the lateral
      geniculate nucleus consisting of two main parvocellular layers and two
      magnocellular layers separated by interlaminar zones or koniocellular layers.

PMID- 29658114
TI  - Proton pump inhibitor use and cancer mortality.
AB  - Proton pump inhibitors (PPIs) are commonly used as a supplement to cancer
      therapy. Yet, their effect on cancer mortality is largely unknown. Using data
      from Danish nationwide registries and Cox models regressing of both propensity
      scores and drug use, we estimated hazard ratios (HRs) with 95% confidence
      intervals (CIs) for cancer-specific and noncancer death among PPI users (>=2
      prescriptions within six months after diagnosis; n = 36,066) compared with
      nonusers (<2 prescriptions, n = 311,853) or users of histamine H2 -receptor
      antagonists (H2 RA; n = 5,152). Adjusted HRs for cancer-specific mortality among
      postdiagnostic PPI users as compared with nonusers or H2 RA users were 1.29 (95%
      CI, 1.27-1.32) and 1.15 (95% CI, 1.10-1.20), respectively. HRs for cancer
      mortality associated with PPI use were highest for ovarian (1.35; 95% CI, 1.20
      1.52) and lowest for esophageal cancer (0.91; 95% CI, 0.81-1.04). The
      associations were stronger among new PPI users after cancer diagnosis, indicating
      potential confounding. To test the effect of PPIs on tumor growth in a model
      system free for confounding factors, we investigated the effect of pantoprazole
      on tumor growth in mice. Pantoprazole (5 mg/kg/day) enhanced tumor growth (p =
      0.033) and reduced the antitumor activity of gemcitabine (p = 0.008) in
      fibrosarcoma-bearing Balb/c mice, but not in immunodeficient Balb/c nude mice. In
      breast carcinoma-bearing FVB/N mice, pantoprazole had no effect on tumor growth
      alone but it reduced the life-prolonging effect of doxorubicin significantly (p =
      0.007). Taken together, these data raise concerns about the increasing use of
      PPIs and calls for further studies addressing their safety among cancer patients.

PMID- 29658115
TI  - Generalisation and specialisation in hoverfly (Syrphidae) grassland pollen
      transport networks revealed by DNA metabarcoding.
AB  - Pollination by insects is a key ecosystem service and important to wider
      ecosystem function. Most species-level pollination networks studied have a
      generalised structure, with plants having several potential pollinators, and
      pollinators in turn visiting a number of different plant species. This is in
      apparent contrast to a plant's need for efficient conspecific pollen transfer.
      The aim of this study was to investigate the structure of pollen transport
      networks at three levels of biological hierarchy: community, species and
      individual. We did this using hoverflies in the genus Eristalis, a key group of
      non-Hymenopteran pollinators. We constructed pollen transport networks using DNA
      metabarcoding to identify pollen. We captured hoverflies in conservation
      grasslands in west Wales, UK, removed external pollen loads, sequenced the pollen
      DNA on the Illumina MiSeq platform using the standard plant barcode rbcL, and
      matched sequences using a pre-existing plant DNA barcode reference library. We
      found that Eristalis hoverflies transport pollen from 65 plant taxa, more than
      previously appreciated. Networks were generalised at the site and species level,
      suggesting some degree of functional redundancy, and were more generalised in
      late summer compared to early summer. In contrast, pollen transport at the
      individual level showed some degree of specialisation. Hoverflies defined as
      "single-plant visitors" varied from 40% of those captured in early summer to 24%
      in late summer. Individual hoverflies became more generalised in late summer,
      possibly in response to an increase in floral resources. Rubus fruticosus agg.
      and Succisa pratensis were key plant species for hoverflies at our sites Our
      results contribute to resolving the apparent paradox of how generalised
      pollinator networks can provide efficient pollination to plant species.
      Generalised hoverfly pollen transport networks may result from a varied range of
      short-term specialised feeding bouts by individual insects. The generalisation
      and functional redundancy of Eristalis pollen transport networks may increase the
      stability of the pollination service they deliver.

PMID- 29658116
TI  - Differentiating the effects of anger and sadness: A perspective of spontaneous
      trait inference.
AB  - In the present research, three experiments were conducted to examine the effects
      of anger and sadness on spontaneous trait inferences (STIs). Using a probe
      recognition paradigm, Experiment 1 revealed that angry participants made more
      errors in response to probes following trait-implying behaviours than sad
      participants did. Using a false recognition paradigm, Experiments 2 and 3
      revealed that angry participants made more errors in response to systematic pair
      trials than sad participants did. The three experiments provided convergent
      evidence that angry individuals were more inclined to form STIs than sad
      individuals were. The current research first demonstrated the different effects
      of specific negative mood states (anger vs. sadness) on STIs, providing further
      insight into the relationship between mood and STIs.

PMID- 29658118
TI  - Transcription factor WRKY22 promotes aluminum tolerance via activation of OsFRDL4
      expression and enhancement of citrate secretion in rice (Oryza sativa).
AB  - Whilst WRKY transcription factors are known to be involved in diverse plant
      responses to biotic stresses, their involvement in abiotic stress tolerance is
      poorly understood. OsFRDL4, encoding a citrate transporter, has been reported to
      be regulated by ALUMINUM (Al) RESISTANCE TRANSCRIPTION FACTOR 1 (ART1) in rice,
      but whether it is also regulated by other transcription factors is unknown. We
      define the role of OsWRKY22 in response to Al stress in rice by using mutation
      and transgenic complementation assays, and characterize the regulation of OsFRDL4
      by OsWRKY22 via yeas one-hybrid, electrophoretic mobility shift assay and ChIP
      quantitative PCR. We demonstrate that loss of OsWRKY22 function conferred by the
      oswrky22 T-DNA insertion allele causes enhanced sensitivity to Al stress, and a
      reduction in Al-induced citrate secretion. We next show that OsWRKY22 is
      localized in the nucleus, functions as a transcriptional activator and is able to
      bind to the promoter of OsFRDL4 via W-box elements. Finally, we find that both
      OsFRDL4 expression and Al-induced citrate secretion are significantly lower in
      art1 oswrky22 double mutants than in the respective single mutants. We conclude
      that OsWRKY22 promotes Al-induced increases in OsFRDL4 expression, thus enhancing
      Al-induced citrate secretion and Al tolerance in rice.

PMID- 29658120
TI  - Erroneous conclusions about the safety of hydroxyethyl starch 130/0.4 in
      paediatric cardiac patients?

PMID- 29658119
TI  - Rice SPX6 negatively regulates the phosphate starvation response through
      suppression of the transcription factor PHR2.
AB  - Phosphorus (P) is an essential macronutrient for plant growth and development,
      but the molecular mechanism determining how plants sense external inorganic
      phosphate (Pi) levels and reprogram transcriptional and adaptive responses is
      incompletely understood. In this study, we investigated the function of OsSPX6
      (hereafter SPX6), an uncharacterized member of SPX domain (SYG1, Pho81 and XPR1)
      containing proteins in rice, using reverse genetics and biochemical approaches.
      Transgenic plants overexpressing SPX6 exhibited decreased Pi concentrations and
      suppression of phosphate starvation-induced (PSI) genes. By contrast, transgenic
      lines with decreased SPX6 transcript levels or spx6 mutant showed significant Pi
      accumulation in the leaf and upregulation of PSI genes. Overexpression of SPX6
      genetically suppressed the overexpression of PHOSPHATE STARVATION RESPONSE
      REGULATOR 2 (PHR2) in terms of the accumulation of high Pi content. Moreover,
      direct interaction of SPX6 with PHR2 impeded PHR2 translocation into the nucleus,
      and inhibited PHR2 binding to the P1BS (PHR1 binding sequence) element. SPX6
      protein was degraded in leaves under Pi-deficient conditions, whereas it
      accumulated in roots. We conclude that rice SPX6 is another important negative
      regulator in Pi starvation signaling through the interaction with PHR2. SPX6
      shows different responses to Pi starvation in shoot and root, which differ from
      those of other SPX proteins.

PMID- 29658117
TI  - Mapping the tumour human leukocyte antigen (HLA) ligandome by mass spectrometry.
AB  - The entirety of human leukocyte antigen (HLA)-presented peptides is referred to
      as the HLA ligandome of a cell or tissue, in tumours often termed
      immunopeptidome. Mapping the tumour immunopeptidome by mass spectrometry (MS)
      comprehensively views the pathophysiologically relevant antigenic signature of
      human malignancies. MS is an unbiased approach stringently filtering the
      candidates to be tested as opposed to epitope prediction algorithms. In the
      setting of peptide-specific immunotherapies, MS-based strategies significantly
      diminish the risk of lacking clinical benefit, as they yield highly enriched
      amounts of truly presented peptides. Early immunopeptidomic efforts were severely
      limited by technical sensitivity and manual spectra interpretation. The
      technological progress with development of orbitrap mass analysers and enhanced
      chromatographic performance led to vast improvements in mass accuracy,
      sensitivity, resolution, and speed. Concomitantly, bioinformatic tools were
      developed to process MS data, integrate sequencing results, and deconvolute multi
      allelic datasets. This enabled the immense advancement of tumour
      immunopeptidomics. Studying the HLA-presented peptide repertoire bears high
      potential for both answering basic scientific questions and translational
      application. Mapping the tumour HLA ligandome has started to significantly
      contribute to target identification for the design of peptide-specific cancer
      immunotherapies in clinical trials and compassionate need treatments. In contrast
      to prediction algorithms, rare HLA allotypes and HLA class II can be adequately
      addressed when choosing MS-guided target identification platforms. Herein, we
      review the identification of tumour HLA ligands focusing on sources, methods,
      bioinformatic data analysis, translational application, and provide an outlook on
      future developments.

PMID- 29658121
TI  - Epidural volume extension - a reply.

PMID- 29658123
TI  - Correction.

PMID- 29658122
TI  - Interpreting the Cormack and Lehane classification during videolaryngoscopy.

PMID- 29658124
TI  - Cerebral oximetry and postoperative delirium after cardiac surgery - a reply.

PMID- 29658125
TI  - Correction.

PMID- 29658126
TI  - Safety of hydroxyethyl starch 130/0.4 in paediatric cardiac patients -
      statistical note.

PMID- 29658127
TI  - Correction.

PMID- 29658128
TI  - End-tidal carbon dioxide monitoring during paediatric general anaesthesia - a
      reply.

PMID- 29658129
TI  - Airway spider or airway spiders?

PMID- 29658130
TI  - Cerebral oximetry and postoperative delirium after cardiac surgery.

PMID- 29658131
TI  - Epidural volume extension.

PMID- 29658132
TI  - Assessing the renal safety of hydroxyethyl starch 130/0.4 in paediatric cardiac
      patients.

PMID- 29658133
TI  - End-tidal carbon dioxide monitoring during paediatric general anaesthesia.

PMID- 29658134
TI  - Safety of hydroxyethyl starch 130/0.4 in paediatric cardiac patients - a reply.

PMID- 29658135
TI  - Cross-cultural invariance of NPI-13: Entitlement as culturally specific,
      leadership and grandiosity as culturally universal.
AB  - The current study explores the problem with the lack of measurement invariance
      for the Narcissistic Personality Inventory (NPI) by addressing two issues:
      conceptual heterogeneity of narcissism and methodological issues related to the
      binary character of data. We examine the measurement invariance of the 13-item
      version of the NPI in three populations in Japan, Poland and the UK. Analyses
      revealed that leadership/authority and grandiose exhibitionism dimensions of the
      NPI were cross-culturally invariant, while entitlement/exploitativeness was
      culturally specific. Therefore, we proposed NPI-9 as indicating scalar
      invariance, and we examined the pattern of correlations between NPI-9 and other
      variables across three countries. The results suggest that NPI-9 is valid brief
      scale measuring general levels of narcissism in cross-cultural studies, while the
      NPI-13 remains suitable for research within specific countries.

PMID- 29658136
TI  - Predatory journals: Enough is enough.

PMID- 29658137
TI  - Cutis tricolor parvimaculata in ring chromosome 15 syndrome: A case report.
AB  - Ring chromosome 15 syndrome is a rare condition, with approximately 50 cases
      reported in the literature. We report a 2-year-old girl with ring chromosome 15
      syndrome with hyperpigmented and hypopigmented patches and cognitive and physical
      manifestations.

PMID- 29658138
TI  - Describing and evaluating healthcare priority setting practices at the county
      level in Kenya.
AB  - BACKGROUND: Healthcare priority setting research has focused at the macro
      (national) and micro (patient level), while there is a dearth of literature on
      meso-level (subnational/regional) priority setting practices. In this study, we
      aimed to describe and evaluate healthcare priority setting practices at the
      county level in Kenya. METHODS: We used a qualitative case study approach to
      examine the planning and budgeting processes in 2 counties in Kenya. We collected
      the data through in-depth interviews of senior managers, middle-level managers,
      frontline managers, and health partners (n = 23) and document reviews. We
      analyzed the data using a framework approach. FINDINGS: The planning and
      budgeting processes in both counties were characterized by misalignment and the
      dominance of informal considerations in decision making. When evaluated against
      consequential conditions, efficiency and equity considerations were not
      incorporated in the planning and budgeting processes. Stakeholders were more
      satisfied and understood the planning process compared with the budgeting
      process. There was a lack of shifting of priorities and unsatisfactory
      implementation of decisions. Against procedural conditions, the planning process
      was more inclusive and transparent and stakeholders were more empowered compared
      with the budgeting process. There was ineffective use of data, lack of provisions
      for appeal and revisions, and limited mechanisms for incorporating community
      values in the planning and budgeting. CONCLUSION: County governments can improve
      the planning and budgeting processes by aligning them, implementing a systematic
      priority setting process with explicit resource allocation criteria, and adhering
      to both consequential and procedural aspects of an ideal priority setting
      process.

PMID- 29658139
TI  - Evaluating community participation: A comparison of participatory approaches in
      the planning and implementation of new primary health-care services in northern
      Australia.
AB  - Community participation is increasingly seen as a prerequisite for more
      acceptable and sustainable health services. It is difficult to evaluate the
      extent of participation in health planning and implementation of services, and
      there are limited tools available to assist in evaluating such processes. Our
      paper reports on community participation as part of the implementation of 2
      primary health programs in regional north Queensland, Australia. We define
      community participation as collective involvement of people, including
      consultation, from a community of place or interest in aspects of health service
      development. We pragmatically evaluate and compare the extent of participation by
      using a framework developed by Rifkin and colleagues in 1988 and subsequently
      refined. Data collected from the implementation of each program were analyzed and
      ranked on a spidergram against 5 process indicators: needs assessment,
      leadership, resource mobilization, management, and organization. Community
      participation was found to vary across the programs but was most extensive in
      both programs in identifying need and potential solutions. Both programs
      demonstrated high levels of integration of the implementation of health programs
      with preexisting community structures. Involving local communities in genuine
      opportunities in managing the programs and mobilizing resources was more
      challenging. Key differences emerged in the people involved in the programs, the
      settings and frameworks used to facilitate implementation. We conclude that
      Rifkin's process indicators are a useful starting point for assessing community
      participation, particularly for health planners who are required to include
      participatory approaches when planning and implementing services. We suggest
      areas that require further consideration.

PMID- 29658140
TI  - Texture analysis of second-harmonic-generation images for quantitative analysis
      of reticular dermal collagen fibre in vivo in human facial cheek skin.
AB  - Second-harmonic-generation (SHG) microscopy is a powerful tool for in vivo
      visualisation of collagen fibres in human skin because of its specific collagen
      selectivity without the need for staining, non-invasiveness and high-resolution
      three-dimensional imaging. Although texture analysis of SHG images is a promising
      method for the quantitative analysis of well-orientated collagen fibre structure
      in the tendon and cornea, there are few attempts to assess cutaneous ageing. In
      this study, we applied two texture analysis techniques, namely autocorrelation
      (2D-AC) analysis and two-dimensional Fourier transform (2D-FT), to evaluate the
      age-dependent changes in reticular dermal collagen fibres in in vivo human cheek
      skin. Age-dependent changes in the reticular dermal collagen fibres of female
      subjects in their 20s, 40s and 60s clearly appeared in these texture analyses.
      Furthermore, the parameter from 2D-AC analysis showed a significantly higher
      correlation with skin elasticity measured by a Cutometer(r) . These results
      clearly indicate that 2D-AC analysis of SHG images is highly promising for the
      quantitative evaluation of age-dependent change in facial collagen fibres as well
      as skin elasticity. An appropriate texture analysis will help to provide
      quantitative insight into collagen fibre structure and will be useful for the
      diagnosis of pathological conditions as well as cutaneous ageing in skin.

PMID- 29658141
TI  - Formal and informal inter-organizational coordination: How nurses adapt in
      complex pathways.
AB  - With the coordination of health care services becoming increasingly complex, the
      challenges of fragmentation cannot be solved by administrative restructuring
      alone. Attention must also be given to the coordination practices of professional
      groups, and, in this respect, the nursing profession is a particularly
      interesting case. Based on a qualitative case study of Danish nurses in hospital,
      municipality, and general practice, this article addresses the following
      question: How does the nursing profession practice formal and informal inter
      organisational coordination in complex pathways, and what is the interplay
      between the 2 types of coordination? The findings contribute to our knowledge of
      coordination at the operative level of health care by identifying specific
      informal practices in inter-organisational coordination and by showing how
      informal coordination is activated to support formal coordination in a concurrent
      organisational and professional ambition of integration. The nurses studied here
      proved very loyal to formal inter-organisational coordination mechanisms,
      prioritising them as first choices of action. When formal procedures were found
      insufficient, however, the nurses temporarily switched to informal coordination.
      This was triggered by random encounters with fragmentation, a strong professional
      engagement in making things work in the interest of the patient, and a constant
      striving to be on top of things. Informal inter-organisational coordination is
      broken down into supplementary and by-passing practices, and 4 specific by
      passing practices are identified. The discussion offers insight into how a lack
      of agency related to formal inter-organisational coordination can be related to
      negotiated settlements, and informal coordination is considered in terms of "rule
      bending" within complex systems.

PMID- 29658142
TI  - Firearm Storage Practices and Risk Perceptions Among a Nationally Representative
      Sample of U.S. Veterans With and Without Self-Harm Risk Factors.
AB  - Despite the disproportionate use of firearms in Veteran suicides and the well
      established link between firearm access and suicide, little is known about how
      Veterans store their firearms or what they think about the relationship between
      firearm access and suicide risk. Using data from 2015 nationally representative
      online survey (response rate 60.9%), we compare characteristics of Veteran
      firearm owners with and without self-harm risk factors with respect to how they
      store their firearms and their beliefs about suicide risk related to firearms.
      Overall, one in three U.S. Veteran firearm owners store household firearms loaded
      and unlocked, one in twenty believe that a firearm increases household suicide
      risk, and one in four consider their loaded and unlocked firearm to be
      inaccessible to suicidal household members. Storage practices and risk
      perceptions are similar among those with and without self-reported suicide risk
      factors. Affecting risk perceptions may be a critical aspect of interventions
      addressing lethal means safety among U.S. Veterans.

PMID- 29658143
TI  - A new prognostic model identifies patients aged 80 years and older with diffuse
      large B-cell lymphoma who may benefit from curative treatment: A multicenter,
      retrospective analysis by the Spanish GELTAMO group.
AB  - The means of optimally managing very elderly patients with diffuse large B-cell
      lymphoma (DLBCL) has not been established. We retrospectively analyzed 252
      patients aged 80-100 years, diagnosed with DLBCL or grade 3B follicular lymphoma,
      treated in 19 hospitals from the GELTAMO group. Primary objective was to analyze
      the influence of the type of treatment and comorbidity scales on progression-free
      survival (PFS) and overall survival (OS). One hundred sixty-three patients (63%)
      were treated with chemotherapy that included anthracyclines and/or rituximab,
      whereas 15% received no chemotherapeutic treatment. With a median follow-up of 44
      months, median PFS and OS were 9.5 and 12.5 months, respectively. In an analysis
      restricted to the 205 patients treated with any kind of chemotherapy, comorbidity
      scales did not influence the choice of treatment type significantly. Independent
      factors associated with better PFS and OS were: age < 86 years, cumulative
      illness rating scale (CIRS) score < 6, intermediate risk (1-2) R-IPI, and
      treatment with R-CHOP at full or reduced doses. We developed a prognostic model
      based on the multivariate analysis of the 108 patients treated with R-CHOP-like:
      median OS was 45 vs. 12 months (P = .001), respectively, for patients with 0-1
      vs. 2-3 risk factors (age > 85 years, R-IPI 3-5 or CIRS > 5). In conclusion,
      treatment with R-CHOP-like is associated with good survival in a significant
      proportion of patients. We have developed a simple prognostic model that may aid
      the selection patients who could benefit from a curative treatment, although it
      needs to be validated in larger series.

PMID- 29658144
TI  - Bone fragility in Turner syndrome: Fracture prevalence and risk factors
      determined by a national patient survey.
AB  - OBJECTIVE: Osteoporosis is considered a comorbidity of adult women with Turner
      syndrome (TS). Limited data are available on fracture prevalence in girls and
      women with this diagnosis. We aimed to determine the prevalence of fractures in
      individuals with TS in the United States and identify risk factors for fracture.
      DESIGN: Girls and women with TS were invited to participate in an anonymous, self
      report, national survey from November 2016 to March 2017. Non-TS controls were
      obtained through direct contacts of TS participants. RESULTS: During childhood (0
      12 years), adolescence (13-25 years) and young adulthood (26-45 years), there was
      no difference between TS and controls in fracture prevalence. Girls and women
      with TS were more likely to report upper extremity fractures, whereas controls
      were more likely to report phalangeal fractures. Older women (>45 years) with TS
      were more likely to fracture than non-TS controls (P = .01). Balance problems
      were more common in individuals with TS than controls (26.5% vs 14.8%, P =
      .0006). In TS, those reporting balance problems were 54% more likely to have a
      prior fracture than those without balance problems (OR=1.54, 95% CI 1.03, 2.30),
      even after controlling for age. There was no significant association between
      balance problems and fractures among controls. CONCLUSIONS: In a nationwide
      survey, there was no difference in fracture prevalence in younger women with TS
      compared with controls. However, the location of fractures differed. After
      controlling for age, impaired balance was associated with an increased fracture
      risk in TS and may be an underrecognized risk factor for fracture in this
      population.

PMID- 29658145
TI  - Long-lasting allergic contact dermatitis caused by methylisothiazolinone in wall
      paint: A case report.

PMID- 29658146
TI  - UVA, metabolism and melanoma: UVA makes melanoma hungry for metastasis.
AB  - Ultraviolet (UV) radiation has a plethora of effects on human tissues. In the UV
      spectrum, wavelengths above 320 nm fall into the UVA range, and for these, it has
      been shown that they induce reactive oxygen species (ROS), DNA mutations and are
      capable to induce melanoma in mice. In addition to this, it was recently shown
      that UVA irradiation and UVA-induced ROS also increase glucose metabolism of
      melanoma cells. UVA irradiation causes a persistent increase in glucose
      consumption, accompanied by increased glycolysis, increased lactic acid
      production and activation of the pentose phosphate pathway. Furthermore, it was
      shown that the enhanced secretion of lactic acid is important for invasion of
      melanoma in vitro. The current knowledge of this link between UVA, metabolism and
      melanoma, possible mechanisms of UVA-induced glucose metabolism and their
      starting points are discussed in this review with focus on ROS- and UVA-induced
      cellular stress signalling, DNA damage signalling and DNA repair systems. When
      looking at the benefits of UVA-induced glucose metabolism, it becomes apparent
      that there are more advantages of these metabolic changes than one would expect.
      Besides the role of lactic acid as initiator of protease expression and invasion,
      its role for immune escape of melanoma cells and the pentose phosphate pathway
      derived nicotinamide adenine dinucleotide phosphate (NADPH) as part of a ROS
      detoxification strategy are discussed.

PMID- 29658147
TI  - Vertical movement symmetry of the withers in horses with induced forelimb and
      hindlimb lameness at trot.
AB  - BACKGROUND: The main criteria for lameness assessment in horses are head movement
      for forelimb lameness and pelvic movement for hindlimb lameness. However,
      compensatory head nod in horses with primary hindlimb lameness is a well-known
      phenomenon. This compensatory head nod movement can be easily misinterpreted as a
      sign of primary ipsilateral forelimb lameness. Therefore, discriminating
      compensatory asymmetries from primary directly pain-related movement asymmetries
      is a prerequisite for successful lameness assessment. OBJECTIVES: To investigate
      the association between head, withers and pelvis movement asymmetry in horses
      with induced forelimb and hindlimb lameness. STUDY DESIGN: Experimental study.
      METHODS: In 10 clinically sound Warmblood riding horses, forelimb and hindlimb
      lameness were induced using a sole pressure model. The horses were then trotted
      on a treadmill. Three-dimensional optical motion capture was used to collect
      kinematic data from reflective markers attached to the poll, withers and tubera
      sacrale. The magnitude and side (left or right) of the following symmetry
      parameters, vertical difference in minimum position, maximum position and range
      up were calculated for head, withers, and pelvis. Mixed models were used to
      analyse data from induced forelimb and hindlimb lameness. RESULTS: For each mm
      increase in pelvic asymmetry in response to hindlimb lameness induction, withers
      movement asymmetry increased by 0.35-0.55 mm, but towards the contralateral side.
      In induced forelimb lameness, for each mm increase in head movement asymmetry,
      withers movement asymmetry increased by 0.05-0.10 mm, in agreement with the head
      movement asymmetry direction, both indicating lameness in the induced forelimb.
      MAIN LIMITATIONS: Results must be confirmed in clinically lame horses trotting
      overground. CONCLUSIONS: The vertical asymmetry pattern of the withers
      discriminated a head nod associated with true forelimb lameness from the
      compensatory head movement asymmetry caused by primary hindlimb lameness.
      Measuring movement symmetry of the withers may, thus, aid in determining primary
      lameness location.

PMID- 29658148
TI  - Biochemical and biomechanical characterisation of equine cervical facet joint
      cartilage.
AB  - BACKGROUND: The equine cervical facet joint is a site of significant pathology.
      Located bilaterally on the dorsal spine, these diarthrodial joints work in
      conjunction with the intervertebral disc to facilitate appropriate spinal motion.
      Despite the high prevalence of pathology in this joint, the facet joint is
      understudied and thus lacking in viable treatment options. OBJECTIVE: The goal of
      this study was to characterise equine facet joint cartilage and provide a
      comprehensive database describing the morphological, histological, biochemical
      and biomechanical properties of this tissue. STUDY DESIGN: Descriptive cadaver
      studies. METHODS: A total of 132 facet joint surfaces were harvested from the
      cervical spines of six skeletally mature horses (11 surfaces per animal) for
      compiling biomechanical and biochemical properties of hyaline cartilage of the
      equine cervical facet joints. Gross morphometric measurements and histological
      staining were performed on facet joint cartilage. Creep indentation and uniaxial
      strain-to-failure testing were used to determine the biomechanical compressive
      and tensile properties. Biochemical assays included quantification of total
      collagen, sulfated glycosaminoglycan and DNA content. RESULTS: The facet joint
      surfaces were ovoid in shape with a flat articular surface. Histological analyses
      highlighted structures akin to articular cartilage of other synovial joints. In
      general, biomechanical and biochemical properties did not differ significantly
      between the inferior and superior joint surfaces as well as among spinal levels.
      Interestingly, compressive and tensile properties of cervical facet articular
      cartilage were lower than those of articular cartilage from other previously
      characterised equine joints. Removal of the superficial zone reduced the tissue's
      tensile strength, suggesting that this zone is important for the tensile
      integrity of the tissue. MAIN LIMITATIONS: Facet surfaces were sampled at a
      single, central location and do not capture the potential topographic variation
      in cartilage properties. CONCLUSIONS: This is the first study to report the
      properties of equine cervical facet joint cartilage and may serve as the
      foundation for the development of future tissue-engineered replacements as well
      as other treatment strategies.

PMID- 29658149
TI  - Coagulation parameters following equine herpesvirus type 1 infection in horses.
AB  - BACKGROUND: Equine herpesvirus type 1 (EHV-1) is the cause of respiratory
      disease, abortion storms, and outbreaks of herpesvirus myeloencephalopathy (EHM).
      Infection of the spinal cord is characterised by multifocal regions of virally
      infected vascular endothelium, associated with vasculitis, thrombosis and
      haemorrhage that result in ischaemia and organ dysfunction. However, the
      mechanism of thrombosis in affected horses is unknown. OBJECTIVES: To evaluate
      tissue factor (TF) procoagulant activity and thrombin-antithrombin complex (TAT)
      levels in horses following infection with EHV-1. STUDY DESIGN: In vitro and in
      vivo studies following experimental EHV-1 infection. METHODS: Horses were
      infected with EHV-1 and levels of peripheral blood mononuclear cell (PBMC)
      associated TF activity; plasma and cerebrospinal fluid (CSF)-derived microvesicle
      (MV)-associated TF activity and TAT complexes in plasma were examined. RESULTS:
      EHV-1 infection increased PBMC TF procoagulant activity in vitro and in vivo. In
      infected horses, this increase was observed during the acute infection and was
      most marked at the onset and end of viraemia. However, no significant differences
      were observed between the horses that showed signs of EHM and the horses that did
      not develop EHM. Significant changes in MV-associated TF procoagulant activity
      and TAT complexes were not observed in infected horses. MAIN LIMITATIONS: A small
      number of horses typically exhibit clinical EHM following experimental infection.
      CONCLUSIONS: The results indicate that EHV-1 infection increases PBMC-associated
      TF procoagulant activity in vivo and in vitro. Additional in vivo studies are
      needed to better understand the role of TF-dependent coagulation during EHM
      pathogenesis in horses.

PMID- 29658150
TI  - Proximal patellar tendon pathology can develop during adolescence in young ballet
      dancers-A 2-year longitudinal study.
AB  - Patellar tendinopathy (tendon pain and dysfunction), or jumper's knee, is
      prevalent in adult jumping athletes. Pathology in the proximal patellar tendon is
      a key risk factor for developing patellar tendinopathy. When pathology develops
      in the proximal patellar tendon is not known, although it is reported to exist in
      adolescent athletes. The aim of this study was to follow young jumping athletes
      (ballet dancers) through adolescence to identify whether pathology develops and
      its relation to the adolescent growth spurt. Fifty-seven elite ballet students
      between ages 11 and 18 were monitored for 2 years. Data were collected every 6
      months, including an ultrasound scan on their left tendons using ultrasound
      tissue characterization (UTC) to quantify intratendinous changes, anthropometric
      data to calculate peak height velocity (adolescent growth spurt), participant
      reports of any injuries or dance modifications, and a VISA-P and single leg
      decline squat for patellar tendon pain. Nine percentage of adolescent dancers
      developed pathology during this study, and development was not associated with
      growth spurt. Peak height velocity and dance participation/volume both at the
      start and throughout the study were similar in those who did develop pathology
      and those who did not. Only 2 of 5 participants who developed pathology reported
      pain associated with their tendon. Pathology in the proximal patellar tendon can
      develop during adolescence.

PMID- 29658151
TI  - Towards the automated identification of Chrysomya blow flies from wing images.
AB  - The Old World screwworm fly (OWSF), Chrysomya bezziana (Diptera: Calliphoridae),
      is an important agent of traumatic myiasis and, as such, a major human and animal
      health problem. In the implementation of OWSF control operations, it is important
      to determine the geographical origins of such disease-causing species in order to
      establish whether they derive from endemic or invading populations. Gross
      morphological and molecular studies have demonstrated the existence of two
      distinct lineages of this species, one African and the other Asian. Wing
      morphometry is known to be of substantial assistance in identifying the
      geographical origin of individuals because it provides diagnostic markers that
      complement molecular diagnostics. However, placement of the landmarks used in
      traditional geometric morphometric analysis can be time-consuming and subject to
      error caused by operator subjectivity. Here we report results of an image-based
      approach to geometric morphometric analysis for delivering wing-based
      identifications. Our results indicate that this approach can produce
      identifications that are practically indistinguishable from more traditional
      landmark-based results. In addition, we demonstrate that the direct analysis of
      digital wing images can be used to discriminate between three Chrysomya species
      of veterinary and forensic importance and between C. bezziana genders.

PMID- 29658152
TI  - Extending health insurance coverage to the informal sector: Lessons from a
      private micro health insurance scheme in Lagos, Nigeria.
AB  - BACKGROUND: As a growing number of low- and middle-income countries commit to
      achieving universal health coverage, one key challenge is how to extend coverage
      to informal sector workers. Micro health insurance (MHI) provides a potential
      model to finance health services for this population. This study presents lessons
      from a pilot study of a mandatory MHI plan offered by a private insurance company
      and distributed through a microfinance bank to urban, informal sector workers in
      Lagos, Nigeria. METHODS: Study methods included a survey of microfinance clients,
      key informant interviews, and a review of administrative records. RESULTS:
      Demographic, health care seeking, and willingness-to-pay data suggested that
      microfinance clients, particularly women, could benefit from a comprehensive MHI
      plan that improved access to health care and reduced out-of-pocket spending on
      health services. However, administrative data revealed declining enrollment, and
      key informant interviews further suggested low use of the health insurance plan.
      Key implementation challenges, including changes to mandatory enrollment
      requirements, insufficient client education and marketing, misaligned incentives,
      and weak back-office systems, undermined enrollment and use of the plan.
      CONCLUSIONS: Mandatory MHI plans, intended to mitigate adverse selection and
      facilitate private insurers' entry into new markets, present challenges for
      covering informal sector workers, including when distributed through agents such
      as a microfinance bank. Properly aligning the incentives of the insurer and the
      agent are critical to effectively distribute and service insurance. Further, an
      urban environment presents unique challenges for distributing MHI, addressing
      client perceptions of health insurance, and meeting their health care needs.

PMID- 29658153
TI  - Cell size, photosynthesis and the package effect: an artificial selection
      approach.
AB  - Cell size correlates with most traits among phytoplankton species. Theory
      predicts that larger cells should show poorer photosynthetic performance, perhaps
      due to reduced intracellular self-shading (i.e. package effect). Yet current
      theory relies heavily on interspecific correlational approaches and causal
      relationships between size and photosynthetic machinery have remained untested.
      As a more direct test, we applied 250 generations of artificial selection (c. 20
      months) to evolve the green microalga Dunaliella teriolecta (Chlorophyta) toward
      different mean cell sizes, while monitoring all major photosynthetic parameters.
      Evolving larger sizes (> 1500% difference in volume) resulted in reduced oxygen
      production per chlorophyll molecule - as predicted by the package effect.
      However, large-evolved cells showed substantially higher rates of oxygen
      production - a finding unanticipated by current theory. In addition, volume
      specific photosynthetic pigments increased with size (Chla+b), while photo
      protectant pigments decreased (beta-carotene). Finally, larger cells displayed
      higher growth performances and Fv /Fm , steeper slopes of rapid light curves
      (alpha) and smaller light-harvesting antennae (sigmaPSII ) with higher
      connectivity (rho). Overall, evolving a common ancestor into different sizes
      showed that the photosynthetic characteristics of a species coevolves with cell
      volume. Moreover, our experiment revealed a trade-off between chlorophyll
      specific (decreasing with size) and volume-specific (increasing with size) oxygen
      production in a cell.

PMID- 29658154
TI  - Vitamin D and bone health: key involvement of physical activity.

PMID- 29658155
TI  - Syntheses and Properties of Metal Nanomaterials with Novel Crystal Phases.
AB  - In recent decades, researchers have devoted tremendous effort into the rational
      design and controlled synthesis of metal nanomaterials with well-defined size,
      morphology, composition, and structure, and great achievements have been reached.
      However, the crystal-phase engineering of metal nanomaterials still remains a big
      challenge. Recent research has revealed that the crystal phase of metal
      nanomaterials can significantly alter their properties, arising from the distinct
      atomic arrangement and modified electronic structure. Until now, it has been
      relatively uncommon to synthesize metal nanomaterials with novel crystal phases
      in spite of the fact that these nanostructures would be promising for various
      applications. Here, the research progress regarding the fine control of noble
      metal (Au, Ag, Ru, Rh, Pd) and non-noble metal (Fe, Co, Ni) nanomaterials with
      novel crystal phases is reviewed. First, synthesis strategies and their phase
      transformations are summarized, while highlighting the peculiar characteristics
      of each element. The phase-dependent properties are then discussed by providing
      representative examples. Finally, the challenges and perspectives in this
      emerging field are proposed.

PMID- 29658156
TI  - Rhizarian 'Novel Clade 10' Revealed as Abundant and Diverse Planktonic and
      Terrestrial Flagellates, including Aquavolon n. gen.
AB  - Rhizarian 'Novel Clade 10' (NC10) is frequently detected by 18S rRNA gene
      sequencing studies in freshwater planktonic samples. We describe a new genus and
      two species of eukaryovorous biflagellate protists, Aquavolon hoantrani n. gen.
      n. sp. and A. dientrani n. gen. n. sp., which represent the first morphologically
      characterized members of NC10, here named Aquavolonida ord. nov. The slightly
      metabolic cells possess naked heterodynamic flagella, whose kinetosomes lie at a
      right angle to each other and are connected by at least one fibril. Unlike their
      closest known relative Tremula longifila, they rotate around their longitudinal
      axis when swimming and only very rarely glide on surfaces. Screening of a wide
      range of environmental DNA extractions with lineage-specific PCR primers reveals
      that Aquavolonida consists of a large radiation of protists, which are most
      diversified in freshwater planktonic habitats and as yet undetected in marine
      environments. Earlier-branching lineages in Aquavolonida include less frequently
      detected organisms from soils and freshwater sediments. The 18S rRNA gene
      phylogeny suggests that Aquavolonida forms a common evolutionary lineage with
      tremulids and uncharacterized 'Novel Clade 12', which likely represents one of
      the deepest lineages in the Rhizaria, separate from Cercozoa (Filosa), Endomyxa,
      and Retaria.

PMID- 29658157
TI  - Temperature influences habitat preference of coral reef fishes: Will generalists
      become more specialised in a warming ocean?
AB  - Climate change is expected to pose a significant risk to species that exhibit
      strong behavioural preferences for specific habitat types, with generalist
      species assumed to be less vulnerable. In this study, we conducted habitat choice
      experiments to determine how water temperature influences habitat preference for
      three common species of coral reef damselfish (Pomacentridae) that differ in
      their levels of habitat specialisation. The lemon damselfish Pomacentrus
      moluccensis, a habitat specialist, consistently selected complex coral habitat
      across all temperature treatments (selected based on local average seasonal
      temperatures naturally experienced in situ: ambient winter 22 degrees C; ambient
      summer 28 degrees C; and elevated 31 degrees C). Unexpectedly, the neon
      damselfish Pomacentrus coelestis and scissortail sergeant Abudefduf sexfasciatus,
      both of which have more generalist habitat associations, developed strong habitat
      preferences (for complex coral and boulder habitat, respectively) at the elevated
      temperature treatment (31 degrees C) compared to no single preferred habitat at
      22 degrees C or 28 degrees C. The observed shifts in habitat preference with
      temperature suggest that we may be currently underestimating the vulnerability of
      some habitat generalists to climate change and highlight that the ongoing loss of
      complex live coral through coral bleaching could further exacerbate resource
      overlap and species competition in ways not currently considered in climate
      change models.

PMID- 29658158
TI  - Limited evidence for CO2 -related growth enhancement in northern Rocky Mountain
      lodgepole pine populations across climate gradients.
AB  - Forests sequester large amounts of carbon annually and are integral in buffering
      against effects of global change. Increasing atmospheric CO2 may enhance
      photosynthesis and/or decrease stomatal conductance (gs ) thereby enhancing
      intrinsic water-use efficiency (iWUE), having potential indirect and direct
      benefits to tree growth. While increasing iWUE has been observed in most trees
      globally, enhanced growth is not ubiquitous, possibly due to concurrent climatic
      constraints on growth. To investigate our incomplete understanding of
      interactions between climate and CO2 and their impacts on tree physiology and
      growth, we used an environmental gradient approach. We combined dendrochronology
      with carbon isotope analysis (delta13 C) to assess the covariation of basal area
      increment (BAI) and iWUE over time in lodgepole pine. Trees were sampled at 18
      sites spanning two climatically distinct elevation transects on the lee and
      windward sides of the Continental Divide, encompassing the majority of lodgepole
      pine's northern Rocky Mountain elevational range. We analyzed BAI and iWUE from
      1950 to 2015, and explored correlations with monthly climate variables. As
      expected, iWUE increased at all sites. However, concurrent growth trends depended
      on site climatic water deficit (CWD). Significant growth increases occurred only
      at the driest sites, where increases in iWUE were strongest, while growth
      decreases were greatest at sites where CWD has been historically lowest. Late
      summer drought of the previous year negatively affected growth across sites.
      These results suggest that increasing iWUE, if strong enough, may indirectly
      benefit growth at drier sites by effectively extending the growing season via
      reductions in gs . Strong growth decreases at high elevation windward sites may
      reflect increasing water stress as a result of decreasing snowpack, which was not
      offset by greater iWUE. Our results imply that increasing iWUE driven by
      decreasing gs may benefit tree growth in limited scenarios, having implications
      for future carbon uptake potential of semiarid ecosystems.

PMID- 29658159
TI  - The influence of developmental environment on courtship song in cactophilic
      Drosophila.
AB  - Closely related species often differ in the signals involved in sexual
      communication and mate recognition. Determining the factors influencing signal
      quality (i.e. signal's content and conspicuousness) provides an important insight
      into the potential pathways by which these interspecific differences evolve. Host
      specificity could bias the direction of the evolution of sexual communication and
      the mate recognition system, favouring sensory channels that work best in the
      different host conditions. In this study, we focus on the cactophilic sibling
      species Drosophila buzzatii and D. koepferae that have diverged not only in the
      sensory channel used for sexual communication and mate recognition but also in
      the cactus species that use as primary hosts. We evaluate the role of the
      developmental environment in generating courtship song variation using an
      isofemale line design. Our results show that host environment during development
      induces changes in the courtship song of D. koepferae males, but not in D.
      buzzatii males. Moreover, we report for the first time that host rearing
      environment affects the conspicuousness of courtship song (i.e. song volume). Our
      results are mainly discussed in the context of the sensory drive hypothesis.

PMID- 29658160
TI  - "Butterfly Wings" Stabilize Heptacene.
AB  - The synthesis of bisalkynylated derivatives of tetrabenzo[a,c,p,r]heptacene and
      tetrabenzo[a,c,l,n]pentacene via two-/fourfold Stille reactions involving a 9
      stannafluorene and suitable tetrabromoacenes is reported. These triphenylene
      "winged" heptacenes are surprisingly stable and maintain a significant portion of
      the electronic properties of heptacenes.

PMID- 29658161
TI  - Parallel evolutionary forces influence the evolution of male and female songs in
      a tropical songbird.
AB  - Given the important role that animal vocalizations play in mate attraction and
      resource defence, acoustic signals are expected to play a significant role in
      speciation. Most studies, however, have focused on the acoustic traits of male
      animals living in the temperate zone. In contrast to temperate environments, in
      the tropics, it is commonplace for both sexes to produce complex acoustic
      signals. Therefore, tropical birds offer the opportunity to compare the sexes and
      provide a more comprehensive understanding of the evolution of animal signals. In
      this study, we quantified patterns of acoustic variation in Rufous-and-white
      Wrens (Thryophilus rufalbus) from five populations in Central America. We
      quantified similarities and differences between male and female songs by
      comparing the role that acoustic adaptation, cultural isolation and neutral
      genetic divergence have played in shaping acoustic divergence. We found that
      males and females showed considerable acoustic variation across populations,
      although females exhibited greater population divergence than males. Redundancy
      analysis and partial-redundancy analysis revealed significant relationships
      between acoustic variation and ecological variables, genetic distance, and
      geographic distance. Both ambient background noise and geographic distance
      explained a high proportion of variance for both males and females, suggesting
      that both acoustic adaptation and cultural isolation influence song. Overall, our
      results indicate that parallel evolutionary forces act on male and female
      acoustic signals and highlight the important role that cultural drift and
      selection play in the evolution of both male and female songs.

PMID- 29658162
TI  - Web building and silk properties functionally covary among species of wolf
      spider.
AB  - Although phylogenetic studies have shown covariation between the properties of
      spider major ampullate (MA) silk and web building, both spider webs and silks are
      highly plastic so we cannot be sure whether these traits functionally covary or
      just vary across environments that the spiders occupy. As MaSp2-like proteins
      provide MA silk with greater extensibility, their presence is considered
      necessary for spider webs to effectively capture prey. Wolf spiders (Lycosidae)
      are predominantly non-web building, but a select few species build webs. We
      accordingly collected MA silk from two web-building and six non-web-building
      species found in semirural ecosystems in Uruguay to test whether the presence of
      MaSp2-like proteins (indicated by amino acid composition, silk mechanical
      properties and silk nanostructures) was associated with web building across the
      group. The web-building and non-web-building species were from disparate
      subfamilies so we estimated a genetic phylogeny to perform appropriate
      comparisons. For all of the properties measured, we found differences between web
      building and non-web-building species. A phylogenetic regression model confirmed
      that web building and not phylogenetic inertia influences silk properties. Our
      study definitively showed an ecological influence over spider silk properties. We
      expect that the presence of the MaSp2-like proteins and the subsequent
      nanostructures improves the mechanical performance of silks within the webs. Our
      study furthers our understanding of spider web and silk co-evolution and the
      ecological implications of spider silk properties.

PMID- 29658163
TI  - A Novel Oncolytic Herpes Capable of Cell-Specific Transcriptional Targeting of
      CD133+/- Cancer Cells Induces Significant Tumor Regression.
AB  - The topic of cancer stem cells (CSCs) is of significant importance due to its
      implications in our understanding of the tumor biology as well as the development
      of novel cancer therapeutics. However, the question of whether targeting CSCs can
      hamper the growth of tumors remains mainly unanswered due to the lack of specific
      agents for this purpose. To address this issue, we have developed the first
      mutated version of herpes simplex virus-1 that is transcriptionally targeted
      against CD133+ cells. CD133 has been portrayed as one of the most important
      markers in CSCs involved in the biology of a number of human cancers, including
      liver, brain, colon, skin, and pancreas. The virus developed in this work, Signal
      Smart 2, showed specificity against CD133+ cells in three different models
      (hepatocellular carcinoma, colorectal cancer, and melanoma) resulting in a loss
      of viability and invasiveness of cancer cells. Additionally, the virus showed
      robust inhibitory activity against in vivo tumor growth in both preventive and
      therapeutic mouse models as well as orthotopic model highly relevant to potential
      clinical application of this virus. Therefore, we conclude that targeting CD133+
      CSCs has the potential to be pursued as a novel strategy against cancer. Stem
      Cells 2018;36:1154-1169.

PMID- 29658164
TI  - Concise Review: Bipotent Megakaryocytic-Erythroid Progenitors: Concepts and
      Controversies.
AB  - Hematopoietic stem and progenitor cells maintain blood formation throughout our
      lifetime by undergoing long- and short-term self-renewal, respectively. As
      progenitor cells progress through the hematopoiesis process, their
      differentiation capabilities narrow, such that the precursors become committed to
      only one or two lineages. This Review focuses on recent advances in the
      identification and characterization of bipotent megakaryocytic-erythroid
      progenitors (MEP), the cells that can further produce two completely different
      functional outputs: platelets and red blood cells. The existence of MEP has
      sparked controversy as studies describing the requirement for this intermediate
      progenitor stage prior to commitment to the erythroid and megakaryocytic lineages
      have been potentially contradictory. Interpretation of these studies is
      complicated by the variety of species, cell sources, and analytical approaches
      used along with inherent challenges in the continuum of hematopoiesis, where
      hematopoietic progenitors do not stop at discrete steps on single paths as
      classically drawn in hematopoietic hierarchy models. With the goal of improving
      our understanding of human hematopoiesis, we discuss findings in both human and
      murine cells. Based on these data, MEP clearly represent a transitional stage of
      differentiation in at least one route to the generation of both megakaryocytes
      and erythroid cells. Stem Cells 2018;36:1138-1145.

PMID- 29658165
TI  - Electrochemical monitoring of malondialdehyde biomarker in biological samples via
      electropolymerized amino acid/chitosan nanocomposite.
AB  - This study reports on the electropolymerization of a low toxic and biocompatible
      nanopolymer with entitle poly arginine-graphene quantum dots-chitosan (PARG-GQDs
      CS) as a novel strategy for surface modification of glassy carbon surface and
      preparation of a new interface for measurement of malondialdehyde (MDA) in
      exhaled breath condensate. Electrochemical deposition, as a well-controlled
      synthesis procedure, has been used for subsequently layer-by-layer preparation of
      GQDs-CS nanostructures on a PARG prepolymerized on the surface of glassy carbon
      electrode using cyclic voltammetry techniques in the regime of -1.5 to 2 V. The
      modified electrode appeared as an effective electroactivity for detection of MDA
      by using cyclic voltammetry, linear sweep voltammetry, and differential pulse
      voltammetry. The prepared modified electrode demonstrated a noticeably good
      activity for electrooxidation of MDA than PARG. Enhancement of peak currents is
      ascribed to the fast heterogeneous electron transfer kinetics that arise from the
      synergistic coupling between the excellent properties of PARG and semiconducting
      polymer, GQDs as high density of edge plane sites and subtle electronic
      characteristics and unique properties of CS such as excellent film-forming
      ability, high permeability, good adhesion, nontoxicity, cheapness, and a
      susceptibility to chemical modification. The prepared sensor showed 1 oxidation
      processes for MDA at potentials about 1 V with a low limit of quantification 5.94
      nM. Finally, application of new sensor for determination of MDA in exhaled breath
      condensate was suited. In general, the simultaneous attachment of GQDs and CS to
      structure of poly amino acids provides new opportunities within the personal
      healthcare.

PMID- 29658166
TI  - 3D Nanofabrication via Chemo-Mechanical Transformation of Nanocrystal/Bulk
      Heterostructures.
AB  - Planar nanocrystal/bulk heterostructures are transformed into 3D architectures by
      taking advantage of the different chemical and mechanical properties of
      nanocrystal and bulk thin films. Nanocrystal/bulk heterostructures are fabricated
      via bottom-up assembly and top-down fabrication. The nanocrystals are capped by
      long ligands introduced in their synthesis, and therefore their surfaces are
      chemically addressable, and their assemblies are mechanically "soft," in contrast
      to the bulk films. Chemical modification of the nanocrystal surface, exchanging
      the long ligands for more compact chemistries, triggers large volume shrinkage of
      the nanocrystal layer and drives bending of the nanocrystal/bulk
      heterostructures. Exploiting the differential chemo-mechanical properties of
      nanocrystal and bulk materials, the scalable fabrication of designed 3D, cell
      sized nanocrystal/bulk superstructures is demonstrated, which possess unique
      functions derived from nanocrystal building blocks.

PMID- 29658167
TI  - Management of oral anticoagulation in patients with atrial fibrillation: newer
      agents, newer conundrums?

PMID- 29658168
TI  - Age differences in the prosocial influence effect.
AB  - Social influence occurs when an individual's thoughts or behaviours are affected
      by other people. There are significant age effects on susceptibility to social
      influence, typically a decline from childhood to adulthood. Most research has
      focused on negative aspects of social influence, such as peer influence on risky
      behaviour, particularly in adolescence. The current study investigated the impact
      of social influence on the reporting of prosocial behaviour (any act intended to
      help another person). In this study, 755 participants aged 8-59 completed a
      computerized task in which they rated how likely they would be to engage in a
      prosocial behaviour. Afterwards, they were told the average rating (in fact
      fictitious) that other participants had given to the same question, and then were
      asked to rate the same behaviour again. We found that participants' age affected
      the extent to which they were influenced by other people: children (8-11 years),
      young adolescents (12-14 years) and mid-adolescents (15-18 years) all
      significantly changed their ratings, while young adults (19-25 years) and adults
      (26-59 years) did not. Across the three youngest age groups, children showed the
      most susceptibility to prosocial influence, changing their reporting of prosocial
      behaviour the most. The study provides evidence that younger people's increased
      susceptibility to social influence can have positive outcomes.

PMID- 29658169
TI  - Love and Dating Patterns for Same- and Both-Gender Attracted Adolescents Across
      Europe.
AB  - Sexual orientation is a multidimensional phenomenon, which includes identity,
      behavior, and attraction. The attraction component, however, is less studied than
      the other two. In this article, we present the development of a two-item measure
      to identify adolescents who prefer same- and both-gender partners for love and
      dating. The questions were administered to nationally representative samples of
      15-year-old adolescents in eight European countries and regions participating in
      the Health Behaviour in School-aged Children (HBSC) cross-national study. The
      distribution of attraction, as operationalized by preference for the gender of
      love and dating partners, was similar across countries. These questions offer an
      alternative or supplementary approach to identify same- and both-gender attracted
      youth, without administering questions related to sexual identity.

PMID- 29658171
TI  - "Anatomists have ever been engaged in contention".

PMID- 29658170
TI  - New Ordered Structure of Amorphous Carbon Clusters Induced by Fullerene-Cubane
      Reactions.
AB  - As a new category of solids, crystalline materials constructed with amorphous
      building blocks expand the structure categorization of solids, for which
      designing such new structures and understanding the corresponding formation
      mechanisms are fundamentally important. Unlike previous reports, new amorphous
      carbon clusters constructed ordered carbon phases are found here by compressing
      C8 H8 /C60 cocrystals, in which the highly energetic cubane (C8 H8 ) exhibits
      unusual roles as to the structure formation and transformations under pressure.
      The significant role of C8 H8 is to stabilize the boundary interactions of the
      highly compressed or collapsed C60 clusters which preserves their long-range
      ordered arrangement up to 45 GPa. With increasing time at high pressure, the
      gradual random bonding between C8 H8 and carbon clusters, due to "energy release"
      of highly compressed cubane, leads to the loss of the ability of C8 H8 to
      stabilize the carbon cluster arrangement. Thus a transition from short-range
      disorder to long-range disorder (amorphization) occurs in the formed material.
      The spontaneous bonding reconstruction most likely results in a 3D network in the
      material, which can create ring cracks on diamond anvils.

PMID- 29658172
TI  - Limited evidence for screening for serious pathologies using red flags in
      patients with low back pain presenting to the emergency department.

PMID- 29658173
TI  - Contrasting results from GWAS and QTL mapping on wing length in great reed
      warblers.
AB  - A major goal in evolutionary biology is to understand the genetic basis of
      adaptive traits. In migratory birds, wing morphology is such a trait. Our
      previous work on the great reed warbler (Acrocephalus arundinaceus) shows that
      wing length is highly heritable and under sexually antagonistic selection.
      Moreover, a quantitative trait locus (QTL) mapping analysis detected a pronounced
      QTL for wing length on chromosome 2, suggesting that wing morphology is partly
      controlled by genes with large effects. Here, we re-evaluate the genetic basis of
      wing length in great reed warblers using a genomewide association study (GWAS)
      approach based on restriction site-associated DNA sequencing (RADseq) data. We
      use GWAS models that account for relatedness between individuals and include
      covariates (sex, age and tarsus length). The resulting association landscape was
      flat with no peaks on chromosome 2 or elsewhere, which is in line with
      expectations for polygenic traits. Analysis of the distribution of p-values did
      not reveal biases, and the inflation factor was low. Effect sizes were however
      not uniformly distributed on some chromosomes, and the Z chromosome had weaker
      associations than autosomes. The level of linkage disequilibrium (LD) in the
      population decayed to background levels within c. 1 kbp. There could be several
      reasons to why our QTL study and GWAS gave contrasting results including
      differences in how associations are modelled (cosegregation in pedigree vs. LD
      associations), how covariates are accounted for in the models, type of marker
      used (multi- vs. biallelic), difference in power or a combination of these. Our
      study highlights that the genetic architecture even of highly heritable traits is
      difficult to characterize in wild populations.

PMID- 29658174
TI  - High Capacity, Dendrite-Free Growth, and Minimum Volume Change Na Metal Anode.
AB  - Na metal anode attracts increasing attention as a promising candidate for Na
      metal batteries (NMBs) due to the high specific capacity and low potential.
      However, similar to issues faced with the use of Li metal anode, crucial problems
      for metallic Na anode remain, including serious moss-like and dendritic Na
      growth, unstable solid electrolyte interphase formation, and large infinite
      volume changes. Here, the rational design of carbon paper (CP) with N-doped
      carbon nanotubes (NCNTs) as a 3D host to obtain Na@CP-NCNTs composites electrodes
      for NMBs is demonstrated. In this design, 3D carbon paper plays a role as a
      skeleton for Na metal anode while vertical N-doped carbon nanotubes can
      effectively decrease the contact angle between CP and liquid metal Na, which is
      termed as being "Na-philic." In addition, the cross-conductive network
      characteristic of CP and NCNTs can decrease the effective local current density,
      resulting in uniform Na nucleation. Therefore, the as-prepared Na@CP-NCNT
      exhibits stable electrochemical plating/stripping performance in symmetrical
      cells even when using a high capacity of 3 mAh cm-2 at high current density.
      Furthermore, the 3D skeleton structure is observed to be intact following
      electrochemical cycling with minimum volume change and is dendrite-free in
      nature.

PMID- 29658175
TI  - MRI Visualization of Injectable Ureidopyrimidinone Hydrogelators by
      Supramolecular Contrast Agent Labeling.
AB  - Information about the in vivo location, shape, degradation, or erosion rate of
      injected in situ gelating hydrogels can be obtained with magnetic resonance
      imaging (MRI). Herein, an injectable supramolecular ureidopyrimidinone-based
      hydrogel (UPy-PEG) is functionalized with a modified Gadolinium(III)-DOTA complex
      (UPy-Gd) for contrast enhanced MRI. The contrast agent is designed to
      supramolecularly interact with the hydrogel network to enable high-quality
      imaging of this hydrogel. The applicability of the approach is demonstrated with
      successful visualization of the Gd-labeled UPy-PEG hydrogel after targeted
      intramyocardial catheter injection in a pig heart.

PMID- 29658176
TI  - A Polypyrrole Elastomer Based on Confined Polymerization in a Host Polymer
      Network for Highly Stretchable Temperature and Strain Sensors.
AB  - For the purpose of stretchable electronics, broad interests have been paid to
      elastic conductors by which high tensile strain over 100% can be readily
      achieved. Here, a scalable-processing, dyeing-like strategy for highly
      stretchable polypyrrole elastomer (1450% in strain) is conceived without
      particular topological design. This approach effectively improves the mechanical
      properties of the classic insoluble polypyrrole by confined polymerization within
      an elastic polymer network. In terms of the easy processing, it is technically
      possible to prepare stretchable electronics with arbitrary shape and size for
      wearable electronics with low cost. The mechanism of interpenetrated networks
      coexisting with microphase separation is comprehensively illustrated at molecular
      scale. The as-fabricated polypyrrole elastomers are utilized as temperature or
      strain sensors for automatic fishing and region-distinct dual signal sensing.
      Further integration of multiple sensors offers immediate alarm for old people
      falling at home, which thereby proves its promising potential in practical
      applications.

PMID- 29658177
TI  - Patterns of statin use and long-term adherence and persistence among older adults
      with diabetes.
AB  - BACKGROUND: Statins reduce the risk of cardiovascular disease in patients with
      diabetes. This study examined the prevalence of statin use and assessed long-term
      adherence and persistence among people aged >=65 years with diabetes. METHODS:
      Pharmaceutical Benefits Scheme data covering a 10% random sample of the
      Australian population were analyzed. Among older adults with diabetes, the yearly
      prevalence of statin use was compared via Poisson regression modeling using 2006
      as the reference year. A cohort of 7400 new statin users (mean age 72.9 years;
      46.2% female) was followed longitudinally. Adherence was assessed via the
      proportion of days covered (PDC). Statin discontinuation was defined as the first
      >=90 days without statin coverage. RESULTS: The prevalence of statin use
      increased from 52.0% in 2006 to 71.2% in 2016 (age and sex-adjusted rate ratio
      1.37; 95% confidence interval 1.33-1.41). No gender differences in statin use
      were observed, but the likelihood of being dispensed statin decreased with
      increasing age. Among the longitudinal cohort, the proportion adherent (PDC
      >=0.80) decreased from 54.0% at 6 months to 37.0% at 9 years. Over a mean follow
      up of 4.9 years, 66.8% discontinued, and the likelihood of stopping statin
      medication within the first year was 42.7%. No age or gender differences in
      statin discontinuation were evident. CONCLUSIONS: Statin use has increased among
      older adults with diabetes. However, adherence is low and discontinuation is
      high. Further investigations into the factors associated with non-adherence or
      discontinuation of statins are important so as to optimize statin use towards
      achieving the intended cardiovascular benefits among older people with diabetes.

PMID- 29658178
TI  - Porous Pt-Ni Nanowires within In Situ Generated Metal-Organic Frameworks for
      Highly Chemoselective Cinnamaldehyde Hydrogenation.
AB  - Although chemoselective hydrogenation of unsaturated aldehydes is the major route
      to highly valuable industrially demanded unsaturated alcohols, it is still
      challenging, as the production of saturated aldehydes is more favorable over
      unsaturated alcohols from the view of thermodynamics. By combining the structural
      features of porous nanowires (NWs) and metal-organic frameworks (MOFs), a unique
      class of porous Pt-Ni NWs in situ encapsuled by MOFs (Pt-Ni NWs@Ni/Fex-MOFs) is
      designed to enhance the unsaturated alcohols selectivity in the cinnamaldehyde
      (CAL) hydrogenation. A detailed catalytic study shows that the porous Pt-Ni
      NWs@Ni/Fex -MOFs exhibit volcano-type activity and selectivity in CAL
      hydrogenation as a function of Fe content. The optimized porous PtNi2.20
      NWs@Ni/Fe4 -MOF is highly active and selective with 99.5% CAL conversion and
      83.3% cinnamyl alcohol selectivity due to the confinement effect, appropriate
      thickness of MOF and its optimized electronic structure, and excellent durability
      with negligible activity and selectivity loss after five runs.

PMID- 29658179
TI  - Vav1 downmodulates Akt in different breast cancer subtypes: a new promising
      chance to improve breast cancer outcome.
AB  - Targeting different members of the Akt pathways is a promising therapeutic chance
      in solid tumors including breast cancer. The variable expression levels of Akt
      isoforms with opposite effects on tumor growth and metastasis, however, make it
      difficult to select the inhibitors to be used for specific breast tumor subtypes.
      Using in vitro and in vivo models, we demonstrated here that Vav1, ectopically
      expressed in invasive breast tumors derived cells, downmodulates Akt acting at
      expression and/or activation levels depending on tumor subtype. The decreased p
      Akt1 (Ser473) levels are a common effect of Vav1 upmodulation, suggesting that,
      in breast tumor-derived cells and independently of their phenotype, Vav1
      interferes with signaling pathways ended to specifically recruit Akt1. Only in ER
      negative cell lines, the silencing of Vav1 induced the expression but not the
      activation of Akt2. A retrospective analysis of early invasive breast tumors
      allowed to establish the prognostic significance of the p-Akt/Vav1 relationship.
      In particular, low Vav1 levels negatively influence the follow-up of patients
      with low p-Akt in their primary tumors and subjected to adjuvant chemotherapy. As
      the use of specific or pan Akt inhibitors may not be sufficient or may even be
      detrimental, increasing the levels of Vav1 could be a new approach to improve
      breast cancer outcomes. This might be particularly relevant for tumors with a
      triple-negative phenotype, for which target-based therapies are not currently
      available.

PMID- 29658180
TI  - Re: Medical student enquiries on the art of clinical inertia.

PMID- 29658181
TI  - Response to Comment on 'Nutrition Screening vs Nutrition Assessment: What's the
      Difference?'

PMID- 29658182
TI  - Editor's Note.

PMID- 29658184
TI  - Comment on 'Nutrition Screening vs Nutrition Assessment: What's the Difference?'

PMID- 29658183
TI  - Determining the Accuracy and Reliability of Indirect Calorimeters Utilizing the
      Methanol Combustion Technique.
AB  - BACKGROUND: Several indirect calorimetry (IC) instruments are commercially
      available, but comparative validity and reliability data are lacking. Existing
      data are limited by inconsistencies in protocols, subject characteristics, or
      single-instrument validation comparisons. The aim of this study was to compare
      accuracy and reliability of metabolic carts using methanol combustion as the
      cross-laboratory criterion. METHODS: Eight 20-minute methanol burn trials were
      completed on 12 metabolic carts. Respiratory exchange ratio (RER) and percent O2
      and CO2 recovery were calculated. RESULTS: For accuracy, 1 Omnical, Cosmed Quark
      CPET (Cosmed), and both Parvos (Parvo Medics trueOne 2400) measured all 3
      variables within 2% of the true value; both DeltaTracs and the Vmax Encore System
      (Vmax) showed similar accuracy in measuring 1 or 2, but not all, variables. For
      reliability, 8 instruments were shown to be reliable, with the 2 Omnicals ranking
      best (coefficient of variation [CV] < 1.26%). Both Cosmeds, Parvos, DeltaTracs, 1
      Jaeger Oxycon Pro (Oxycon), Max-II Metabolic Systems (Max-II), and Vmax were
      reliable for at least 1 variable (CV <= 3%). For multiple regression, humidity
      and amount of combusted methanol were significant predictors of RER (R2 = 0.33, P
      < .001). Temperature and amount of burned methanol were significant predictors of
      O2 recovery (R2 = 0.18, P < .001); only humidity was a predictor for CO2 recovery
      (R2 = 0.15, P < .001). CONCLUSIONS: Omnical, Parvo, Cosmed, and DeltaTrac had
      greater accuracy and reliability. The small number of instruments tested and
      expected differences in gas calibration variability limits the generalizability
      of conclusions. Finally, humidity and temperature could be modified in the
      laboratory to optimize IC conditions.

PMID- 29658185
TI  - Evaluating Changes in Handgrip Strength in Children With Cystic Fibrosis: A Pilot
      Study.
AB  - BACKGROUND: Body mass index (BMI) is used to determine nutrition status in
      children with cystic fibrosis (CF); however, lean body mass (LBM) is more
      strongly associated with pulmonary function. Handgrip strength (HGS) measures
      muscle function and is reflective of LBM. The aims of this study were to assess
      relationships among HGS, nutrition status, and pulmonary function; changes in HGS
      posthospitalization; and any relationship between HGS and nutrient intake.
      METHODS: Twenty-three children with CF aged 6-18 years participated. BMI z
      scores, nutrition risk scores, and pulmonary function were assessed about 5
      months before, days 5-7 of hospitalization, and about 6 weeks
      posthospitalization. HGS z scores and arm anthropometrics were measured during
      and after hospitalization. Nutrient intakes were assessed during hospitalization.
      RESULTS: Mean HGS z score at hospitalization was -1.95 +/- 0.92 and
      posthospitalization was -1.59 +/- 1.06 (P = .007). Mean BMI z score
      prehospitalization was -0.17 +/- 0.63, at hospitalization was -0.09 +/- 0.64, and
      posthospitalization was 0.06 +/- 0.54 (P = .065). Mean forced expiratory volume
      in 1 second (FEV1 ) prehospitalization was 93.52 +/- 17.35, at hospitalization
      was 85.65 +/- 21.57, and posthospitalization was 95.63 +/- 18.18 (P = .001). No
      significant relationship was found between HGS z scores and BMI z scores (P =
      .892) or HGS z scores and FEV1 (P = .340). CONCLUSIONS: HGS z scores and FEV1
      significantly increased at follow-up. HGS z scores were lower than the standard
      even though mean BMI z scores classified participants as normal nutrition status.

PMID- 29658186
TI  - Use of an In-line Digestive Cartridge With Enteral Nutrition Improves the Weight
      Trajectory of 2 Children With Cystic Fibrosis Complicated by Another Medical
      Diagnosis.
AB  - This clinical observation describes the enteral nutrition (EN) management of 2
      toddlers at high nutrition risk due to cystic fibrosis (CF), exocrine pancreatic
      insufficiency, and comorbid medical conditions. The first case report describes a
      boy with severe malabsorption after intestinal resection. The second case report
      reviews a boy with CF and neuroblastoma. When pancreatic enzyme replacement
      therapy with EN was not effective or appropriate, use of an in-line digestive
      cartridge was initiated. While using the digestive cartridge, both children
      showed improvements in their anthropometric measures. This observation reviews
      the nutrition management throughout their clinical course and describes the use
      of a digestive cartridge with EN.

PMID- 29658187
TI  - Overview of Intensive Care Unit-Related Physical and Functional Impairments and
      Rehabilitation-Related Devices.
AB  - Rehabilitation after critical illness requires a multidisciplinary effort.
      Nutrition support of critically ill patients aims to correct the imbalance
      between protein synthesis and protein degradation to maximize strengthening and
      muscle mass, whereas physical and occupational therapists focus on optimizing
      strength and mobility through functional activity to help intensive care (ICU)
      patients return to their precritical illness level of function and improve
      quality of life. Early mobility has become the new standard of care for ICU
      patients. Therapists utilize various devices and technologies to increase the
      feasibility of early mobility and enhance the rehabilitation process to ensure
      that patients reach their rehabilitation goals. Tools such as electrical
      stimulation, cycle ergometers, dynamic tilt tables, and resistive bands aid in
      strengthening. Therapists use safe patient-handling equipment and ambulation aids
      to address gait impairments. Adaptive toileting, dressing, bathing, and feeding
      tools facilitate greater independence with activities of daily living.
      Augmentative and alternative communication devices promote well-being and
      communication of basic needs. Splints prevent joint contracture and maintain
      functional range of motion. Overall, many rehabilitation devices are safe and
      feasible for use in an ICU setting and serve to maximize strength and functional
      independence. The purpose of this narrative review is to discuss the benefits and
      limitations of available rehabilitation devices in the context of critical
      illness rehabilitation goals.

PMID- 29658189
TI  - Side Effects of Long-Term Proton Pump Inhibitor Use: A Review.
AB  - Proton pump inhibitors (PPIs) are widely used, and concerns about overuse have
      been raised. Therefore, side effects are important to be aware of and several
      suggested side effects of long-term use have been studied. In this MiniReview, we
      sum up the evidence of side effects related to long-term PPI treatment. Suspected
      side effects are mainly related to increased susceptibility to infections,
      secondary hypergastrinaemia, impeded absorption of micronutrients or
      idiosyncratic reactions. Most of the potential side effects have only been
      evaluated in observational studies demonstrating conflicting and weak
      associations with a substantial risk of confounding. However, a high probability
      of causality seems to be established for the side effects increased risk of
      gastrointestinal infections and rebound acid hypersecretion following
      discontinuation of treatment due to secondary hypergastrinaemia. The risk of side
      effects should not be a reason to withhold PPIs from patients with a true
      indication, and worry about poorly proven side effects should not lead to
      unnecessary discontinuation. The most important safety issue regarding PPI
      therapy is to critically evaluate the indication when initiating treatment and
      reconsidering the indication in long-term-treated patients.

PMID- 29658190
TI  - The 2018 update of the American College of Physicians glycaemic management
      recommendations: An invitation to continued inertia?
AB  - The management of type 2 diabetes has become increasingly controversial. Tight
      control has been advocated for years; however, there was a recent revision
      published by the American College of Physicians in which limitations were made to
      liberalize glycaemic goals for most diabetics, targeting a level between 7% and
      8%. In recent years, the evolution of diabetes care has been such that more
      potent drugs, with low risk of hypoglycaemia when used in the absence of insulin
      or secretagogues, have made their way into the market place. Use of such agents
      has made it easier to achieve greater glycaemic control reasonably safely.
      Unfortunately, it appears that there has been a significant amount of inertia
      over the past decade, which continues to persist. Relaxing the glycaemic control
      targets, as recommended by the American College of Physicians, may only help to
      propagate this inertia.

PMID- 29658191
TI  - An international study on the feasibility of a standardized combined plasma clot
      turbidity and lysis assay: communication from the SSC of the ISTH.

PMID- 29658192
TI  - Using group-based trajectory modelling to enhance causal inference in interrupted
      time series analysis.
AB  - RATIONALE, AIMS, AND OBJECTIVES: Several enhancements have been proposed for
      interrupted time series analysis (ITSA) to improve causal inference. Presently,
      group-based trajectory modelling (GBTM) is introduced as a complement to ITSA.
      GBTM assumes a certain number of discrete groups in the sample have unique
      trajectories of the outcome. GBTM is used herein for 2 purposes: (1) to compare
      outcomes across all trajectory groups via a stand-alone GBTM and (2) to identify
      comparable non-treated units to serve as controls in the ITSA outcome model.
      Examples of each are offered. METHOD: The effect of California's Proposition 99
      (passed in 1988) for reducing cigarette sales is evaluated by comparing
      California to other states not exposed to smoking reduction initiatives. In the
      stand-alone GBTM, distinct trajectory groups are identified based on cigarette
      sales for the entire observation period (1970-2000). In the second approach, a
      GBTM is generated using only baseline period observations (1970-1988), and
      treatment effects (difference in post-intervention trends) are then estimated for
      the treatment unit versus non-treated units in the treated unit's trajectory
      group. RESULTS: In the stand-alone GBTM, 3 distinct trajectory groups were
      identified: low-decreasing, medium-decreasing, and high-decreasing (California
      and 26 other states were in the low-decreasing group). When using baseline data
      for matching, California and 19 non-treated states comprised the low group.
      California had a significantly larger decrease in post-intervention cigarette
      sales than these controls (P < 0.01). CONCLUSIONS: GBTM enhances ITSA by
      providing perspective for the outcome trajectory in the treated unit's group
      versus all others and can identify non-treated units to be used for estimating
      treatment effects.

PMID- 29658188
TI  - Strategy to targeting the immune resistance and novel therapy in colorectal
      cancer.
AB  - Assessing the CRC subtypes that can predict the outcome of colorectal cancer
      (CRC) in patients with immunogenicity seems to be a promising strategy to develop
      new drugs that target the antitumoral immune response. In particular, the
      disinhibition of the antitumoral T-cell response by immune checkpoint blockade
      has shown remarkable therapeutic promise for patients with mismatch repair (MMR)
      deficient CRC. In this review, the authors provide the update of the molecular
      features and immunogenicity of CRC, discuss the role of possible predictive
      biomarkers, illustrate the modern immunotherapeutic approaches, and introduce the
      most relevant ongoing preclinical study and clinical trials such as the use of
      the combination therapy with immunotherapy. Furthermore, this work is further to
      understand the complex interactions between the immune surveillance and develop
      resistance in tumor cells. As expected, if the promise of these developments is
      fulfilled, it could develop the effective therapeutic strategies and novel
      combinations to overcome immune resistance and enhance effector responses, which
      guide clinicians toward a more "personalized" treatment for advanced CRC
      patients.

PMID- 29658193
TI  - Update of Diabetes UK Evidence-Based Nutritional Guidelines for 2018: a
      celebration of two leading journals working together to improve nutritional
      science and dietetic care for people living with diabetes.

PMID- 29658194
TI  - A global climate niche for giant trees.
AB  - Rainforests are among the most charismatic as well as the most endangered
      ecosystems of the world. However, although the effects of climate change on
      tropical forests resilience is a focus of intense research, the conditions for
      their equally impressive temperate counterparts remain poorly understood, and it
      remains unclear whether tropical and temperate rainforests have fundamental
      similarities or not. Here we use new global data from high precision laser
      altimetry equipment on satellites to reveal for the first time that across
      climate zones 'giant forests' are a distinct and universal phenomenon, reflected
      in a separate mode of canopy height (~40 m) worldwide. Occurrence of these giant
      forests (cutoff height > 25 m) is negatively correlated with variability in
      rainfall and temperature. We also demonstrate that their distribution is sharply
      limited to situations with a mean annual precipitation above a threshold of 1,500
      mm that is surprisingly universal across tropical and temperate climates. The
      total area with such precipitation levels is projected to increase by ~4 million
      km2 globally. Our results thus imply that strategic management could in principle
      facilitate the expansion of giant forests, securing critically endangered
      biodiversity as well as carbon storage in selected regions.

PMID- 29658195
TI  - Extracellular vesicles from human saliva promote hemostasis by delivering
      coagulant tissue factor to activated platelets.
AB  - : Essentials Human salivary extracellular vesicles (EVs) expose coagulant tissue
      factor (TF). Salivary EVs expose CD24, a ligand of P-selectin. CD24 and coagulant
      TF co-localize on salivary EVs. TF+ /CD24+ salivary EVs bind to activated
      platelets and trigger coagulation. SUMMARY: Background Extracellular vesicles
      (EVs) from human saliva expose coagulant tissue factor (TF). Whether such TF
      exposing EVs contribute to hemostasis, however, is unknown. Recently, in a mice
      model, tumor cell-derived EVs were shown to deliver coagulant TF to activated
      platelets at a site of vascular injury via interaction between P-selectin
      glycoprotein ligand-1 (PSGL-1) and P-selectin. Objectives We hypothesized that
      salivary EVs may deliver coagulant TF to activated platelets via interaction with
      P-selectin. Methods We investigated the presence of two ligands of P-selectin on
      salivary EVs, PSGL-1 and CD24. Results Salivary EVs expose CD24 but PSGL-1 was
      not detected. Immune depletion of CD24-exposing EVs completely abolished the TF
      dependent coagulant activity of cell-free saliva, showing that coagulant TF and
      CD24 co-localize on salivary EVs. In a whole blood perfusion model, salivary EVs
      accumulated at the surface of activated platelets and promoted fibrin generation,
      which was abolished by an inhibitory antibody against human CD24. Conclusions A
      subset of EVs in human saliva expose coagulant TF and CD24, a ligand of P
      selectin, suggesting that such EVs may facilitate hemostasis at a site of skin
      injury where the wound is licked in a reflex action.

PMID- 29658196
TI  - Systematic study of protein sumoylation: Development of a site-specific predictor
      of SUMOsp 2.0.
AB  - Protein sumoylation is an important reversible post-translational modification on
      proteins, and orchestrates a variety of cellular processes. Recently,
      computational prediction of sumoylation sites has attracted much attention for
      its cost-efficiency and power in genomic data mining. In this work, we developed
      SUMOsp 2.0, an accurate computing program with an improved group-based
      phosphorylation scoring algorithm. Our analysis demonstrated that SUMOsp 2.0 has
      greater prediction accuracy than SUMOsp 1.0 and other existing tools, with a
      sensitivity of 88.17% and a specificity of 92.69% under the medium threshold.
      Previously, several large-scale experiments have identified a list of potential
      sumoylated substrates in Saccharomyces cerevisiae and Homo sapiens; however, the
      exact sumoylation sites in most of these proteins remain elusive. We have
      predicted potential sumoylation sites in these proteins using SUMOsp 2.0, which
      provides a great resource for researchers and an outline for further mechanistic
      studies of sumoylation in cellular plasticity and dynamics. The online service
      and local packages of SUMOsp 2.0 are freely available at:
      http://sumosp.biocuckoo.org/.

PMID- 29658197
TI  - Role of geranylgeranylacetone as non-toxic HSP70 inducer in liver surgery:
      clinical application.
AB  - Heat shock proteins (HSPs) are rapidly synthesized into cells in response to
      various types of physical or chemical insults and induce potent resistance to the
      stressors. A stress-inducible HSP70 is not expressed in normal conditions, but
      once HSP70 is excessively induced under various environmental stresses, HSP70
      expressing cells can survive even under lethal conditions. In this review, we
      focused on the potential role of HSPs particularly HSP70 in liver surgery. A non
      toxic HSP70 inducer, geranylgeranylacetone (GGA), has been introduced to exert a
      potent cytoprotective action against liver injury after ischemia/reperfusion,
      massive hepatectomy and liver transplantation in animal experiments. We have
      tried to explain possible therapeutic benefits of GGA in liver surgery. However,
      any dependable clinical application has not been done. One of the reasons is that
      any randomized clinical trial has not being carried out in clinical cases.
      Therefore, we have advocated the national scale randomized clinical trial for
      dependable clinical application of GGA.

PMID- 29658198
TI  - The Sapir-Whorf hypothesis and inference under uncertainty.

PMID- 29658199
TI  - The Added Value of the Lateral Chest Radiograph for Diagnosing Community Acquired
      Pneumonia in the Pediatric Emergency Department.
AB  - BACKGROUND: Opinions differ as to the need of a lateral radiograph for diagnosing
      community acquired pneumonia in children referred to the emergency department. A
      lateral radiograph increases the ionizing radiation burden but at the same time
      may improve specificity and sensitivity in this population. OBJECTIVES: To
      determine the value of the frontal and lateral chest radiographs compared to
      frontal view stand-alone images for the management of children with suspected
      community acquired pneumonia seen in a pediatric emergency department. METHODS:
      Chest radiographs from 451 children with clinically suspected pneumonia were
      retrospectively reviewed. Interpretation of frontal views was compared to
      interpretation of combined frontal and lateral view, the latter being the gold
      standard. RESULTS: Findings consistent with bacterial pneumonia were diagnosed in
      94 (20.8%) of the frontal stand-alone radiographs and in 109 (24.2%) of the
      combined frontal and lateral radiographs. The sensitivity, specificity, positive
      predictive value, and negative predictive value of the frontal radiograph alone
      were 86.2%, 93.9%, 81.7%, and 95.5%, respectively. False positive and false
      negative rates were 15% and 21%, respectively, for the frontal view alone. The
      number of lateral radiographs needed to diagnose one community acquired pneumonia
      was 29. CONCLUSIONS: The lateral chest radiograph improves the diagnosis of
      pediatric community acquired pneumonia to a certain degree and may prevent
      overtreatment with antibiotics.

PMID- 29658200
TI  - Detection of Ureaplasma Species by a Semi-Quantitative PCR Test in Urine Samples:
      Can It Predict Clinical Significance?
AB  - BACKGROUND: Ureaplasma species (Usp) are the most prevalent genital Mycoplasma
      isolated from the urogenital tract of both men and women. Usp may be commensals
      in the genital tract but may also be contributors to a number of pathological
      conditions of the genital tract. Because they can also just colonize the genital
      tract of healthy people, their pathogenic role can be difficult to prove.
      OBJECTIVES: The aim of the study was to evaluate the efficacy of a quantitative
      polymerase chain reaction (qPCR) method for the discrimination between infection
      and colonization by measuring prevalence of Usp in asymptomatic versus
      symptomatic patients. METHODS: Urine samples were tested for U. parvum and U.
      urealyticum using a semi-quantitative multiplex PCR technique for sexually
      transmitted diseases (AnyplexTM STI-7 Detection Kit, Seegene, South Korea). A
      total of 250 symptomatic and 250 asymptomatic controls were included. RESULTS: A
      strong positive result for U. parvum was significantly more prevalent in
      symptomatic compared to asymptomatic patients. This finding was observed
      especially in women and in the young group (15-35 years of age). No significant
      differences were observed between the prevalence in symptomatic and asymptomatic
      patients of U. parvum with low strength of positivity and for U. urealyticum in
      all groups by age, gender, and strength of positivity. CONCLUSIONS: The
      significant difference between the symptomatic and asymptomatic group in the
      highest positivity group for U. parvum using the AnyplexTM STI-7 detection kit in
      urine may indicate a high probability of infection rather than colonization,
      especially in women and young patients.

PMID- 29658201
TI  - Enhancement of Standard ECGs by a New Method for Multi-Cycle Superimposition and
      Summation.
AB  - BACKGROUND: Since the introduction of the electrocardiogram (ECG) in 1902, the
      fundamentals of ECG data acquisition, display, and interpretation in the clinical
      arena have not changed much. OBJECTIVES: To present a new method to enhance and
      improve acquisition, analysis, and display of the standard ECG. METHODS: We
      performed ECG enhancement by superimposition and summation of multiple standard
      ECG cycles of each lead, by temporal alignment to peak R wave and voltage
      alignment to an improved baseline, at the T-P segment. RESULTS: We enhanced ECG
      recordings of 504 patients who underwent coronary angiograms for routine
      indications. Several new ECG features were noted on the enhanced recordings.
      Examination of a subgroup of 152 patients with a normal rest 12-lead ECG led to
      the discovery of a new observation, which may help to distinguish between
      patients with and without coronary artery disease (CAD): namely, a spontaneous
      cycle-to-cycle voltage spread (VS) at the S-T interval, normalized to VS at the T
      P interval. The mean normalized VS was significantly greater in those with CAD
      (n=61, 40%) than without (n=91, 60%), 5.61 +/- 3.79 vs. 4.01 +/- 2.1 (P < 0.05).
      CONCLUSIONS: Our novel method of multiple ECG-cycle superimposition enhances the
      ECG display and improves detection of subtle electrical abnormalities, thus
      facilitating the standard rest ECG diagnostic power. We describe, for the first
      time, voltage spread at the S-T interval, an observed phenomenon that can help
      detect CAD among individuals with normal rest 12-lead ECG.

PMID- 29658202
TI  - Physical Training in a Medical Fitness Room for Patients with Chronic Diseases:
      Functional and Metabolic Outcomes.
AB  - BACKGROUND: Physical inactivity is a pivotal factor in the development and
      progression of various chronic diseases. However, most fitness facilities exclude
      unhealthy individuals. Therefore, an exercise program that admits such patients
      is imperative. OBJECTIVES: To evaluate the effectiveness of a fitness facility
      that admits adult subjects with multiple chronic diseases. METHODS: We conducted
      a retrospective screening of patient records from the Medical Fitness Facility at
      Meir Medical Center, Israel. Intake of subjects was done by a multidisciplinary
      team. For each individual, personalized diet and exercise plans were developed
      and patients attended the facility twice a week. Each participant was evaluated
      at enrolment and after 4 months for well-being, metabolic parameters, exercise
      capacity, and laboratory blood tests. RESULTS: A total of 838 individuals were
      enrolled, mean age 57 years. Their medical conditions included dyslipidemia
      (48.8%), hypertension (37.6%), and diabetes mellitus (24.9%), followed by
      musculoskeletal problems (arthropathy 19%, lower back pain 16.1%) and ischemic
      heart disease (13.4%). Less common diagnoses were vascular diseases, pulmonary
      diseases, and malignancy. Only 40.5% of participants adhered to the regimen with
      advanced age being the best predictor for adherence. At the follow-up visit, body
      mass index was lower (31.2 vs. 30.2 kg/m2, P <0.0001), exercise capacity
      increased (measured as maximal MET; 7.1 vs. 8.1, P < 0.0001), and well-being
      improved (measured by Short Form Survey [SF-36]; 69.3 vs. 76.0, P <0.0001).
      CONCLUSIONS: We show that a fitness program for patients with multiple chronic
      diseases is feasible and effective in improving prognostic parameters, albeit
      significantly challenged by adherence limitations.

PMID- 29658203
TI  - Crohn's Disease Behavior and Location is Altered when Associated with Primary
      Sclerosing Cholangitis.
AB  - BACKGROUND: Up to 3.4% of Crohn's disease (CD) patients will be diagnosed with
      concomitant primary sclerosing cholangitis (PSC). Despite the worldwide increase
      incidence of CD, data on the clinical characteristics of PSC-CD patients are
      scarce. OBJECTIVES: To clinically characterize CD in patients who have
      concomitant PSC. METHODS: A retrospective case-control analysis was conducted
      with 18 CD patients with concomitant PSC who attended the Inflammatory Bowel
      Disease Center at the Tel Aviv Sourasky Medical Center between 2011-2014 (PSC-CD
      patients). They were matched by age, gender, and disease duration to 90 control
      patients (those with CD who did not have concomitant PSC). Disease phenotype
      (according to the Montreal classification), demographics, and clinical data were
      compared in the two groups. RESULTS: PSC-CD patients were characterized by a
      disease that was more frequently limited to the colon (L2) (50% vs. 16%, P =
      0.004) and by a non-stricturing and non-penetrating inflammatory phenotype (83%
      vs. 33%, P = 0.0001) compared to controls who had an increased prevalence of the
      penetrating phenotype (B3) (6% vs. 33% P < 0.05). Use of 5-aminosalicylic acid
      agents as a single therapy was significantly more prevalent among PSC-CD patients
      than in controls (39% vs. 7%, P < 0.005). In contrast, biologic therapy was
      significantly less common among PSC-CD patients compared to controls (17% vs.
      52%, P = 0.0086). CONCLUSIONS: Patients with PSC-CD are clinically distinct from
      patients with isolated CD, and are characterized by predominant colonic
      involvement and an inflammatory, non-stricturing and non-penetrating phenotype.

PMID- 29658204
TI  - The Impact of Surgeons: Pathologists Dialog on Lymph Node Evaluation of
      Colorectal Cancer Patients.
AB  - BACKGROUND: Lymph node (LN) retrieval and assessment is essential for accurate
      staging and treatment planning in colorectal cancer (CRC). According to U.S.
      National Cancer Institute recommendations, the minimal number of LNs needed for
      accurately staging of node-negative CRC is 12. Awareness and implementation of
      the guidelines has been shown to improve after assigning an opinion leader who
      has a special interest in CRC. OBJECTIVES: To evaluate the impact of dialogue
      between surgeons and pathologists in LN evaluation. METHODS: Consecutively
      treated CRC patients at the Department of Surgery B at Rambam Medical Center from
      January 1, 2000 through July 30, 2005 were identified from hospital discharge
      files. Demographic, surgical, and pathological data were extracted. Patients were
      divided into two groups. Group I patients underwent surgery before the initiation
      of a structured surgical oncology service (January 1, 2000 to October 30, 2004).
      Group II patients underwent surgery after the initiation of the service (November
      1, 2004 to July 30, 2005). RESULTS: The study comprised 212 patients (Group I:
      n=170; Group II: n=42). The median number of LNs examined was 9 in Group I and 14
      in Group II (P = 0.003). Only 35% of patients in Group I received adequate LN
      evaluation compared to 79% in Group II (P = 0.0001). Patients with left-sided or
      rectal cancer were less likely to receive adequate LN evaluation than patients
      with right-sided cancers. CONCLUSIONS: A durable improvement in LN evaluation was
      realized through a multi-pronged change initiative aimed at both surgeons and
      pathologists.

PMID- 29658205
TI  - Reduced Suprathreshold Odor Identification in Patients with Pseudotumor Cerebri:
      A Non-Randomized Prospective Study.
AB  - BACKGROUND: Recent evidence suggests that olfaction is impaired in patients with
      pseudotumor cerebri (PTC). OBJECTIVES: To measure suprathreshold olfactory
      function by using the University of Pennsylvania Smell Identification Test
      (UPSIT), assessing its usefulness for routine clinical use. METHODS: Forty PTC
      patients underwent USPIT olfactory testing. RESULTS: Twenty-nine out of 40 (73%)
      PTC patients (36 women, 4 men; mean age 34 years) had reduced suprathreshold
      smell sensation according to UPSIT scores: 19 (47%) had mild microsmia, 9 (23%)
      had moderate microsmia, and one (3%) was classified as having severe microsmia.
      The mean UPSIT score of all patients was 32.4 (95% confidence interval 31.4
      33.4). Multivariate regression analysis found that UPSIT scores were not related
      to disease activity, disease duration, initial intracranial pressure (ICP), or
      visual function. CONCLUSIONS: Many PTC patients have reduced suprathreshold
      olfactory dysfunction that can be discovered by UPSIT, a rapidly administered
      smell test, which is suitable for clinical office use.

PMID- 29658206
TI  - Awareness and Functional Outcome of Hip Fracture-Related Falls among Patients
      with a History of Recurrent Falling.
AB  - BACKGROUND: There is little evidence about awareness and functional outcome of
      hip fracture-related falls among patients with a history of recurrent falling.
      OBJECTIVES: To measure the awareness of recurrent falling in patients and to
      compare their functional outcomes with those who suffered hip fracture after a
      sporadic isolated fall. METHODS: A prospective comparative study of patients
      after a hip fracture-related fall was conducted. Awareness of falls was measured
      and functional outcome was assessed by total and motor Functional Independence
      Measure (FIM) score changes and efficiency and scores at admission and on
      discharge. RESULTS: Of 97 eligible participants, 49 (50.5%) were recurrent
      fallers. Of these recurrent falls, 19 (38.8%) were not reported, 16 (32.7%) were
      reported but no action was taken, and 7 (14.3%) were reported and a partial
      assessment performed. A full assessment was performed in only 7 cases (14.3%).
      FIM scores on admission and discharge were significantly higher in once-fallers.
      A multiple linear regression analysis showed that being a once-faller was
      independently associated with higher total FIM at admission (beta coefficient =
      0.290, P = 0.004), higher motor FIM at admission (beta coefficient = 0.295, P =
      0.003), higher total FIM at discharge (beta Coefficient = 0.264, P = 0.009), and
      higher motor FIM at discharge (beta coefficient = 0.230, P = 0.023). CONCLUSIONS:
      Awareness of the syndrome of recurrent falling is extremely low. Recurrent falls
      before a hip fracture-related fall is associated with substantial loss of
      functional independence. Being a recurrent faller adversely affects
      rehabilitation outcome of hip fracture patients.

PMID- 29658207
TI  - Ablation-Induced Change in the Course of Fascicular Tachycardia.
AB  - BACKGROUND: Multiform fascicular tachycardia (FT) was recently described as a
      ventricular tachycardia (VT) that has a reentrant mechanism using multiple
      fascicular branches and produces alternate fascicular VT forms. Ablating the
      respective fascicle may cause a change in the reentrant circuit resulting in a
      change in morphology. Ablation of the septal fascicle is crucial for successful
      treatment. OBJECTIVES: To describe four cases of FT in which ablation induced a
      change in QRS morphologies and aggravated clinical course. METHODS: Four out of
      57 consecutive FT cases at three institutions were retrospectively analyzed and
      found to involve multiform FT. These cases underwent electrophysiological study,
      fascicular potential mapping, and electroanatomical mapping. All patients
      initially had FT with right bundle branch block (RBBB) and superior axis
      morphology. RESULTS: Radiofrequency catheter ablation (RFCA) targeting the distal
      left posterior fascicle (LPF) resulted in a second VT with an RBBB-inferior axis
      morphology that sometimes became faster and/or incessant and/or verapamil
      refractory in characteristics. RFCA in the upper septum abolished the second VT
      with no complications and uneventful long-term follow-up. CONCLUSIONS: The change
      in FT morphology during ablation may be associated with a change in clinical
      course when shifting from one route to another and may aggravate symptoms.
      Targeting of the proximal conduction system (such as bifurcation, LPF, left
      anterior fascicle, high septal/auxiliary pathway) may serve to solve this
      problem.

PMID- 29658208
TI  - Exercise in the Management of Chronic Diseases: An Underfilled Prescription.

PMID- 29658209
TI  - Upper Extremity Deep Vein Thrombosis: Symptoms, Diagnosis, and Treatment.
AB  - BACKGROUND: Upper extremity deep vein thrombosis (UEDVT) is defined as thrombosis
      of the deep venous system (subclavian, axillary, brachial, ulnar, and radial
      veins), which drains the upper extremities. It can be caused by thoracic outlet
      anatomic obstruction, such as Paget-Schroetter syndrome, (primary) or by central
      intravenous catheters (secondary). UEDVT may be asymptomatic or present with
      acute severe pain and arm swelling. Clinical suspicion should be confirmed by
      diagnostic imaging procedures such as duplex ultrasound, computed tomography
      scan, or magnetic resonance imaging. UEDVT is managed by anticoagulant treatment.
      In addition to that, early thrombolysis aimed at preventing post-deep vein
      thrombosis syndrome and thoracic outlet decompression surgery should be given to
      patients with primary UEDVT. Anticoagulation without thrombolysis is the
      treatment of choice for patients with catheter-related thrombosis. Mandatory
      functioning catheters can remain in place with anticoagulant treatment. All other
      catheters should be immediately removed. The management of patients with UEDVT
      requires an experience multidisciplinary team comprised of internists,
      radiologists, hematologists, and vascular surgeons. Understanding the risk
      factors for the development of UEDVT, the diagnostic procedures, and the
      treatment modalities will improve the outcome of those patients.

PMID- 29658210
TI  - Septic Sacroiliitis: A Diagnostic Challenge for the Clinician.

PMID- 29658211
TI  - A Case of a Retrocardiac Mass.

PMID- 29658212
TI  - Tick-Borne Relapsing Fever with Severe Jarisch-Herxheimer Reaction.

PMID- 29658214
TI  - My Medicine, My body: The Serious Physician becomes a Serious Patient.

PMID- 29658213
TI  - Successful Use of a Reduced Dose Regimen of Rituximab in a Case of Rheumatoid
      Arthritis with Raynaud's Syndrome.

PMID- 29658215
TI  - ?

PMID- 29658216
TI  - [Prevention of urinary tract infection in the elderly : what's new in long-term
      care facilities?]
AB  - Urinary tract infections are common in the elderly. They are a frequent reason
      for antibiotic prescription in nursing homes and hospitals. Doctors are
      confronted daily to the challenge that it is to diagnose urinary tract infections
      in older patients. The incidence of asymptomatic bacteriuria and the presence of
      unspecific symptoms and signs in this population transform guidelines for
      prevention and treatment into some kind of a battle. In this article we will : 1)
      make a reminder of the particular features of urinary tract infection in the
      elderly person ; 2) present the recommendations made by the experts and 3)
      emphasize the prevention of catheter-related urinary tract infection. The latter
      has already proven itself. We will also focus on the prevention of multi
      resistant bacterial infections through the correct use of antibiotics.

PMID- 29658217
TI  - [Management of infectious diarrhea in nursing homes].
AB  - Infectious diarrheas are of great concern in nursing homes and can engender
      outbreaks. Their importance in terms of morbidity, mortality and health economics
      justify the implementation of prevention and control measures. Although past
      studies emphasize the importance of infectious diarrheas occurring during
      hospitalization, data on nursing homes epidemiology remain scarce. This article
      is founded on recent data of the literature, on recommendations for the
      management of infectious diarrheas and for prevention and control of outbreaks in
      nursing homes.

PMID- 29658218
TI  - [Burden of healthcare-associated infections in outpatient care].
AB  - There is little evidence on healthcare-associated infections in outpatient care.
      The Swiss Federal Office for Public Health commissioned a systematic review to
      estimate the incidence of healthcare-associated infections in non-institutional
      settings. A total of 126 papers were eligible for data abstraction. The
      identified reports and studies were heterogeneous and generally of low quality.
      The main outcomes were surgical site infections, central venous catheter-related
      bloodstream infections, and urinary tract infections. While no comparison to
      inpatients was possible for surgical site infection, the incidence of urinary
      tract infection and central venous catheter-related bloodstream infection in
      haemodialysis and home intravenous therapy was similar to the incidence of these
      infections observed in acute care settings.

PMID- 29658219
TI  - [Vancomycine-resistant enterocci (VRE) : a new reality in our hospitals].
AB  - Limiting the emergence and spread of multi-resistant bacteria is a global concern
      and the management of colonized patient represents a real challenge, especially
      in the hospital setting, where risks of acquisition and transmission are
      increased. Switzerland is not protected from undesirable trends : for instance,
      recent outbreaks of vancomycin-resistant enterococci (VRE) have been reported in
      several hospitals in western Switzerland. Since 2011, more than 250 patients have
      been tested positive during these outbreak episodes and the molecular analysis of
      the documented strains shows an unexpected diversity, including both sporadic and
      epidemic strains. This emerging threat requires strict monitoring, prevention and
      infection control strategies in our healthcare facilities.

PMID- 29658220
TI  - [Multiresistant bacteria : practical aspects for doctors working in ambulatory
      practice].
AB  - Although preventive measures against the transmission of multidrug-resistant
      organisms (MDROs) are well established and protocolized in hospital settings,
      their implementation in private ambulatory practice are rarely addressed. Despite
      what is sometimes communicated, the risk of transmission of this type of bacteria
      outside of a hospital environment is real. Standard precautions are the key to
      minimizing this risk. In a number of situations in the ambulatory setting, MDRO
      screening (nasal or rectal) is needed and recommended. A system of communication
      among healthcare professionals concerning patients known to be carriers of MDROs
      should also be one of the strategies aimed at reducing the spread of these
      threatening bacteria throughout the health system.

PMID- 29658221
TI  - [Prevention of influenza in acute care settings : a multimodal intervention].
AB  - Preventing an influenza outbreak in an acute care requires a multimodal
      intervention, taking into account the actors involved (influenza virus, staff,
      patients, visitors), and the stage of the epidemic. Different means are used for
      this purpose : immunization, use of alcohol-based hand rub, identification of
      influenza cases, wearing of medical masks, social distance, and antiviral
      treatment. In addition, an epidemiological surveillance of influenza cases, in
      the general population and within the health facilities, must be associated.

PMID- 29658222
TI  - ?

PMID- 29658223
TI  - ?

PMID- 29658224
TI  - ?

PMID- 29658225
TI  - ?

PMID- 29658226
TI  - ?

PMID- 29658227
TI  - ?

PMID- 29658228
TI  - ?

PMID- 29658229
TI  - High-speed Raman-encoded molecular imaging of freshly excised tissue surfaces
      with topically applied SERRS nanoparticles.
AB  - Surface-enhanced Raman scattering (SERS) nanoparticles (NPs) are increasingly
      being engineered for a variety of disease-detection and treatment applications.
      For example, we have previously developed a fiber-optic Raman-encoded molecular
      imaging (REMI) system for spectral imaging of biomarker-targeted SERS NPs
      topically applied on tissue surfaces to identify residual tumors at surgical
      margins. Although accurate tumor detection was achieved, the commercial SERS NPs
      used in our previous studies lacked the signal strength to enable high-speed
      imaging with high pixel counts (large fields of view and/or high spatial
      resolution), which limits their use for certain time-constrained clinical
      applications. As a solution, we explored the use of surface-enhanced resonant
      Raman scattering (SERRS) NPs to enhance imaging speeds. The SERRS NPs were
      synthesized de novo, and then conjugated to HER2 antibodies to achieve high
      binding affinity, as validated by flow cytometry. Under identical tissue-staining
      and imaging conditions, the targeted SERRS NPs enabled reliable identification of
      HER2-overexpressed tumor xenografts with 50-fold-enhanced imaging speed compared
      with our standard targeted SERS NPs. This enables our REMI system to image tissue
      surfaces at a rate of 150  cm2 per minute at a spatial resolution of 0.5 mm.

PMID- 29658230
TI  - [Preparation of a polyclonal antibody against human LYZL4 and its expression in
      the testis].
AB  - Objective: To prepare a polyclonal antibody against human lysozyme-like protein 4
      (LYZL4) expressed in the prokaryotic system and identify the distribution of
      LYZL4 in the testis. METHODS: The full-length cDNA of LYZL4 was cloned into the
      pET32a plasmid and the expression of the recombinant LYZL4 (rLYZL4) was induced
      by IPTG. The rLYZL4 was purified by Ni-NTA and chitin affinity chromatography
      respectively and its bactericidal activity was observed by bilayer agar plate
      diffusion assay. The purified rLYZL4 was used as an immunogen to generate the
      polyclonal antibody, followed by examination of the antibody titer by ELISA and
      its specificity by Western blot. The distribution of LYZL4 in human tissue, sperm
      and seminal plasma was identified and its subcellular localization in the testis
      was determined by immunohistochemistry. RESULTS: rLYZL4 was expressed efficiently
      in the prokaryotic system and exhibited no bacteriolytic activity against M.
      lysodeikticus and E. coli. The anti-rLYZL4 polyclonal antibody could bind the
      recombinant protein with a high sensitivity and specificity. LYZL4 was identified
      in the testis, epididymis and sperm protein extracts and localized in the
      acrosomal region of round and elongating spermatids. CONCLUSIONS: An anti-rLYZL4
      polyclonal antibody was successfully prepared using the prokaryotic expression
      system. LYZL4 was detected in the acrosomal region of round and elongating
      spermatids, suggesting an association with the structure and function of the
      acrosome.

PMID- 29658231
TI  - [Molecular mechanisms of androgens regulating the eNOS expression in rat corpus
      cavernosum].
AB  - Objective: To investigate whether androgens can regulate the expression of eNOS
      in rat corpus cavernosum through AKT3, PIK3CA, CALM, and CAV1 and influence
      erectile function. METHODS: Thirty-six 8-week-old male SD rats were randomly
      divided into groups A (4-week control), B (6-week control), C (4-week
      castration), D (6-week castration), E (4-week castration + testosterone
      replacement), and F (6-week castration + testosterone replacement). Both the
      testis and epididymis were removed from the rats in groups C, D, E and F, and on
      the second day after surgery, the animals of groups E and F were subcutaneously
      injected with testosterone propionate at 3 mg per kg of the body weight qd alt
      while all the others with isodose oil instead. At 4 weeks (for groups A, C and E)
      and 6 weeks (for groups B, D and F) after treatment, we detected the maximum
      intracavernous pressure (ICPmax), the mean carotid arterial pressure (MAP) and
      their ratio (ICPmax/MAP), measured the level of serum testosterone (T), and
      determined the expressions of eNOS, P-eNOS, AKT3, PIK3CA, CALM and CAV1 in the
      corpus cavernosum by Western blot and immunohistochemistry. RESULTS: No
      statistically significant differences were observed in the body weight and MAP
      among different groups. The serum T level and ICPmax/MAP were remarkably lower in
      groups C and D than in the other four groups (P<0.01) as well as in groups E and
      F than in A and B (P<0.05) but exhibited no significant differences either
      between E and F or between A and B. Immunohistochemistry showed that eNOS and P
      eNOS were mainly expressed in the vascular endothelial cell membrane and
      cavernous vascular lumen, while AKT3, PIK3CA, CALM and CAV1 chiefly in the
      vascular endothelial cell cytoplasm and membrane, with a few in the smooth muscle
      cells. Western blot analysis manifested that the expressions of eNOS, P-eNOS,
      AKT3, PIK3CA, CALM and CAV1 were markedly lower in groups C and D than in A, B, E
      and F (P<0.01) as well as in D than in C (P<0.05) but those in groups E and F did
      not showed any significant difference from those in A and B, nor E from F or A
      from B. CONCLUSIONS: Androgens can improve erectile function by upregulating the
      expressions of AKT3, PIK3CA, CALM and CAV1 protein molecules and activating eNOS
      after its phosphorylation, though the exact molecular mechanisms are yet to be
      further studied.

PMID- 29658232
TI  - [Swimming plus medication reduces the expressions of cytokines in rats with
      chronic abacterial prostatitis].
AB  - Objective: To observe the effects of swimming plus medication on the expressions
      of cytokines in rats with chronic abacterial prostatitis (CAP). METHODS: Forty
      healthy adult male SD rats were randomly divided into five groups of equal
      number, normal control, CAP model control, medication, exercise therapy, and
      exercise + medication. The CAP model was made by Xiaozhiling injection, and at 7
      days after modeling, the rats in the medication and exercise + medication groups
      were treated intragastrically with Qianlie Shutong Capsules (0.016 g/ml) at 20 ml
      per kg of the body weight qd, those in the exercise therapy and exercise +
      medication groups were made swim at a regular time once a day, 35 minutes on the
      first day and 5 minutes more on the second until 50 minutes once, for 4
      successive weeks, and those in the normal control, model control and exercise
      therapy groups received normal saline only. After 14 and 28 days of treatment,
      all the rats were killed and their prostates harvested for observation of
      histopathological changes and determination of the expressions of TNF- alpha, IL
      1beta and IL-6 in the prostatic tissue homogenate by ELISA. RESULTS: After 14
      days of treatment, the expression levels of TNF-alpha, IL-1beta and IL-6 were
      significantly elevated in the groups of CAP model control ([183.08+/-8.07] pg/ml,
      [57.55+/-3.53] pg/ml and [256.15+/-13.95] ng/L), medication ([118.49+/-8.06]
      pg/ml, [42.64+/-4.64 ] pg/ml and [200.74+/-9.33] ng/L), exercise therapy
      ([169.63+/-10.64] pg/ml, [50.45+/-5.71] pg/ml and [245.23+/-6.49] ng/L), and
      exercise + medication ([107.82+/-7.81] pg/ml, [40.35+/-6.93] pg/ml and [187.04+/
      10.85] ng/L) as compared with those in the normal control ([20.36+/-1.82] pg/ml,
      [14.64+/-1.91] pg/ml and [70.58+/-2.09] ng/L) (P<0.05). At 28 days, the levels of
      TNF- alpha, IL-1beta, IL-6 were remarkably lower in the exercise + medication
      group ([29.30+/-3.78] pg/ml, [16.91+/-1.24] pg/ml and [ 88.65+/-6.74] ng/L) than
      in the medication group ([39.67+/-3.19] pg/ml, [26.27+/-3.49] pg/ml and [110.26+/
      6.33] ng/L) (P<0.05) and close to those of the normal control group ([19.34+/
      1.76] pg/ml, [13.68+/-1.06] pg/ml and [71.34+/-2.50] ng/L). During the treatment,
      no obvious pathological changes were found in the prostate tissue of the normal
      control rats, while significant chronic prostatic inflammation was observed in
      the CAP models, and the inflammation was relieved in different degrees after
      intervention, most significantly in the exercise + medication group. CONCLUSIONS:
      Swimming can relieve prostatic inflammation and swimming plus medication can
      effectively reduce the expressions of cytokines and alleviate histological damage
      in the prostatic tissue of CAP rats.

PMID- 29658233
TI  - [Anti-prostate cancer effect of roemerine: An experimental study].
AB  - Objective: To investigate the anti-prostate cancer (PCa) effect of roemerine in
      vitro and in vivo in the mouse model of PCa. METHODS: We detected the effects of
      roemerine on the proliferation, apoptosis and migration of PCa cells DU145,
      LNCaP, PC-3 and 22RV1, screened out the sensitive cell line and constructed a
      tumor-bearing model in mice for verification of the antitumor efficacy of
      roemerine in vivo. RESULTS: Roemerine inhibited the proliferation and migration
      of the DU145, LNCaP, PC-3 and 22RV1 cells and induced their apoptosis in
      different degrees, particularly those of the LNCaP cells. The average tumor
      weight was less in the roemerine intervention group ([1.99+/-0.95] g) than in the
      control ([2.95+/-1.04] g), the least in the high-dose roemerine (30 mg/kg) plus
      paclitaxel intervention group ([0.90+/-0.16] g). The mean heart, liver, and
      kidney indexes were markedly lower in the roemerine (0.58+/-0.06, 6.20+/-0.42 and
      1.49+/-0.33) than in the paclitaxel group (0.66+/-0.04, 6.99+/-0.72 and 1.95+/
      0.34), while the mean spleen and thymus indexes were remarkably higher in the
      former (0.54+/-0.11 and 0.06+/-0.01) than in the latter (0.41+/-0.09 and 0.05+/
      0.01). Pathological staining showed a lower degree of malignancy and metastasis
      in both the roemerine and the roemerine + paclitaxel intervention group than in
      the control, as well as a lower degree of visceral injury in the roemerine and
      roemerine + paclitaxel groups than in the paclitaxel group. CONCLUSIONS:
      Roemerine has some anti-PCa effect and alleviates adverse reactions in paclitaxel
      combination administration.

PMID- 29658234
TI  - [Retzius-sparing robot-assisted laparoscopic radical prostatectomy for early
      stage prostate cancer (with video)].
AB  - Objective: To investigate the application of Retzius-sparing robot-assisted
      radical prostatectomy (RS-RARP) in the treatment of early-stage prostate cancer.
      METHODS: We retrospectively analyzed the clinical data about 10 cases of early
      stage prostate cancer treated by RS-RARP with the Da Vinci Robot Surgical System
      from September to October 2016. RESULTS: All the operations were successfully
      completed without positive surgical margins. The operation time was 170-250 min
      ([196+/-25] min), the intraoperative blood loss was 150-500 ml ([260+/-128] ml),
      the postoperative hospital stay was 6-7 days, and the catheterization time was 14
      days. Urinary continence occurred after catheter removal in 1 patient and was
      recovered 1 month later. CONCLUSIONS: RS-RARP is a safe, effective and reliable
      method for the treatment of prostate cancer and conducive to the early recovery
      of urinary continence.

PMID- 29658235
TI  - [Modified Bianchi orchiopexy for median or low cryptorchidism].
AB  - Objective: To investigate the effect of modified Bianchi (single incision in the
      midline of the scrotum) orchiopexy (MBO) versus that of traditional surgery in
      the treatment of median or low cryptorchidism. METHODS: Eighty-two children with
      median or low cryptorchidism were treated from February 2013 to February 2014, 46
      (53 testes) by MBO and the other 36 by the traditional method of inguinal
      incision (control, 40 testes). Comparisons were made in the operation time and
      postoperative complications between the two surgical strategies. RESULTS: The
      mean operation time was significantly shorter in the MBO group than in the
      control ([25+/-6] vs [35+/-4] min, P<0.05). No testicular atrophy, hernias or
      hydrocele was found in either group during the 1-2 years of follow-up. Testis
      retraction was observed in 3 cases in the MBO group as compared with 2 in the
      control (P>0.05). The incision scar was obvious in all the controls, with 1 case
      of postoperative inguinal hematoma, but almost invisible in all the MBO cases.
      CONCLUSIONS: Modified Bianchi orchiopexy is superior to traditional surgery in
      the treatment of median or low cryptorchidism for its advantages of short
      operation time, few complications, and satisfactory appearance of the healed
      incision.

PMID- 29658236
TI  - [Safety and efficacy of China-made sildenafil citrate in the treatment of
      erectile dysfunction].
AB  - Objective: To evaluate the safety, efficacy and tolerability of China-made
      sildenafil citrate (Jinge) in the treatment of ED. METHODS: We conducted a multi
      center, randomized, double-blind and placebo-controlled clinical trial among 222
      ED patients in five urological or andrological clinics of China. The patients
      were randomly assigned to receive sildenafil citrate (SC, n = 111) or placebo (n
      = 111) for 8 weeks. We obtained and analyzed the demographic and clinical
      characteristics of the patients, the scores of International Index of Erectile
      Function (IIEF), the success rate of sexual intercourse, and the incidence of
      adverse events. RESULTS: No statistically significant differences were found
      between the patients of the SC and those of the placebo group in the mean age
      ([47.2+/-11.32] yr vs [46.67+/-13.08] yr, P>0.05), psychological etiology (27.93%
      vs 23.42%, P>0.05), organic etiology (21.62% vs 29.73%, P>0.05) or mixed etiology
      (50.45% vs 46.85%, P>0.05), nor in height, weight, nationality, or history of
      smoking, drinking or allergy. Compared with the placebo controls, the SC-treated
      patients showed significant increases in the excellence rate of effectiveness
      (29.91% vs 78.90%, P<0.01), success rate of sexual intercourse (29.16% vs 63.87%,
      P<0.01), and total effectiveness rate (34.58% vs 77.98%, P<0.01). The
      effectiveness rates on organic, psychogenic and mixed types ED were remarkably
      higher in the SC group (64.52%, 83.33%, and 82.14%) than in the placebo control
      (46.15%, 21.21%, and 25.00%) (P<0.01). Mild or temporary adverse events were
      observed in 32 cases in the SC group as compared with 13 in the placebo control.
      CONCLUSIONS: China-made sildenafil citrate is an effective, safe and well
      tolerated drug for ED of different etiologies in the Chinese population.

PMID- 29658237
TI  - [Impacts of Chk1 and Chk2 gene expressions on sperm concentration and motility].
AB  - Objective: To study the correlation of the gene expressions of Chk1 and Chk2 with
      sperm concentration and motility. METHODS: According to sperm concentration and
      motility (percentage of progressively motile sperm), we divided 80 semen samples
      into four groups of equal number: normal control, oligozoospermia (OS),
      asthenospermia (AS), and oligoasthenozoospermia (OAS). We detected the sperm DNA
      fragmentation index (DFI) and viability and determined the expressions of Chk1
      and Chk2 in the sperm by RT-PCR and Western blot. RESULTS: Statistically
      significant differences were not found in sperm DFI among the control, OS, AS,
      and OAS groups (21.24+/-6.93, 19.67+/-7.64, 21.52+/-6.92, and 19.28+/-11.55,
      P>0.05), but observed in sperm concentration, progressive motility, and viability
      between the DFI >30% and DFI <=30% groups (P<0.01). Compared with the normal
      control, sperm viability was remarkably decreased in the OS, AS, and OAS groups
      ([83.48+/-9.87]% vs [63.86+/-9.16]%, [50.45+/-16.99]%, and [39.21+/-15.74]%,
      P<0.05). RT-PCR showed remarkable differences among the control, OS, AS, and OAS
      groups in the relative expression level of Chk1 mRNA (0.73+/-0.22, 0.62+/-0.14,
      1.03+/-0.39, and 0.92+/-0.071, P<0.01), which was correlated positively with
      sperm concentration (b = 80.661, P<0.01) but negatively with sperm motility (b = 
      19.275, P < 0.01), as well as in that of Chk2 mRNA (0.66+/-0.30, 0.27+/-0.09,
      0.59+/-0.19, and 0.42 +/- 0.11, P<0.01), which was correlated negatively with
      sperm concentration (b = -90.809, P<0.01) but positively with sperm motility (b =
      27.507, P <0.01). The relative expression levels of the Chk1 protein were
      significantly different among the four groups (0.63+/-0.05, 0.42+/-0.03, 1.13+/
      0.08, and 0.87+/-0.07, P<0.01), which was correlated positively with sperm
      concentration (b = 55.74, P<0.01) but negatively with sperm motility (b =-22.649,
      P<0.01), and so were those of the Chk2 protein (1.23+/-0.36, 0.37+/-0.16, 0.87+/
      0.08, and 0.68+/-0.12, P<0.01), which was correlated negatively with sperm
      concentration (b =-53.001, P<0.01) but positively with sperm motility (b =
      16.676, P < 0.01). CONCLUSIONS: Chk1 and Chk2 are significantly expressed in
      human sperm. In case of sperm DNA damage, up-regulated Chk1 expression may
      enhance sperm apoptosis and lead to asthenospermia, while increased Chk2
      expression may inhibit spermatogenesis and result in oligospermia.

PMID- 29658238
TI  - [Routine semen parameters and sperm morphological index of infertile males with
      partial globozoospermia].
AB  - Objective: To investigate the routine semen parameters and sperm morphological
      indexes of the patients with partial globozoospermia (PGZ). METHODS: We included
      in this study 100 infertile males with PGZ and another 180 non-PGZ infertile men
      as controls. According to the proportion of round-headed sperm (RHS) in the
      semen, we classified the PGZ males into five subgroups: 25%-40%, 41%-55%, 56%
      70%, 71%-85%, and 86%-99% RHS. We obtained sperm concentration, total sperm
      motility, the percentage of progressively motile sperm, teratozoospermia index
      (TZI), and sperm deformity index (SDI) from the subjects and compared them among
      different groups. RESULTS: Statistically significant differences were found
      between the PGZ patients and non-PGZ controls in total sperm motility ([35.76+/
      24.88]% vs [62.03+/-10.20]%, P<0.01), the percentage of progressively motile
      sperm ([26.11+/-20.39]% vs [45.62+/-6.87]%, P<0.01), the percentage of
      morphologically normal sperm ([1.45+/-1.45]% vs [5.98+/-2.21]%, P<0.01), and SDI
      (1.33+/-0.11 vs 1.27+/-0.57, P<0.01), but not in age ([29.82+/-4.90] vs [30.33+/
      3.59 ] yr, P>0.05), sperm concentration ([46.01+/-40.38] vs [54.00+/-25.15]
      *106/ml, P>0.05), or TZI (1.35+/-0.11 vs 1.34+/-0.54, P>0.05). There were also
      significant differences among the five PGZ subgroups in total sperm motility,
      progressive sperm motility, normal sperm morphology, TZI, and SDI (P<0.01), but
      not in age or sperm concentration (P>0.05). Morphologically, the sperm head
      changed from heterogeneous to homogeneous with the increased proportion of round
      headed sperm. CONCLUSIONS: Different proportions of round-headed sperm are
      closely related to routine semen parameters and sperm morphological index in PGZ
      patients, which can help clinicians choose the proper assisted reproductive
      technology and predict the rate of fertilization for infertile males.

PMID- 29658239
TI  - [Gene polymorphisms of estrogen receptor alpha correlated with hypospadias in
      children].
AB  - Objective: To investigate the association of the polymorphisms of the gene of
      estrogen receptor alpha 1 (ESR1) with the risk of hypospadias in children of
      Northeast China. METHODS: This study included 95 hypospadias patients aged 3.2+/
      0.6 years and 105 children aged 3.1+/-0.7 years as normal controls. Using PCR and
      gene sequencing, we determined the genotypes of the polymorphisms of ESR1
      rs2077647 and rs6932902 in the two groups of subjects. RESULTS: The results of
      PCR and gene sequencing showed statistically significant differences in the
      genotype and allele frequency distribution of the polymorphisms rs2077647 (chi2 =
      8.552) and rs6932902 (chi2 = 16.251) (P<0.05) in the hypospadias and control
      groups. The hypospadias patients, in comparison with the normal controls,
      exhibited a markedly higher frequency of the SNP C allele in rs2077647 (OR =
      1.410 [1.130-1.759], P<0.05), but a remarkably lower frequency of the SNP G
      allele in rs6932902 (OR = 2.263 [1.503-3.408], P<0.01). CONCLUSIONS: The
      rs2077647 and rs6932902 polymorphisms of the ESR1 gene are associated with the
      risk of hypospadias, and so is its haplotype in children in Northeast China.

PMID- 29658240
TI  - [Clinical and genetic features of 45,X maleness: A case report and review of the
      literature].
AB  - Objective: To explore the relationship between the clinical and genetic features
      of a short-statured azoospermia male with the karyotype of 45,X. METHODS: Using
      GTG-banded chromosome analysis, we performed karyotyping for a 150 cm-high
      infertile male with azoospermia and investigated the presence and location of the
      genes on the Y chromosome by FISH and PCR. RESULTS: GTG-banded chromosome
      analysis showed the karyotype of the patient to be 45,X,add(14)(p11). The results
      of PCR manifested the deletion of AZFa, AZFb, AZFc, and AZFd in the SRY gene.
      FISH revealed the translocation of the short arm of the Y chromosome to that of
      chromosome 14 and deletion of most proportions of its long arm, with the
      disruption site close to the centromere region. The karyotype of the patient was
      45,X,der(Y)t(Y;14)(q11;q11.2), 14.ish (SRY+, CEP Y+ , DYZ1-). CONCLUSIONS: The
      karyotype of the patient was unbalanced Y/14 translocation. The SRY gene is the
      key to maleness. The deletion of AZFa- d induces spermatogenic disturbance, and
      the deletion of the q arm of the Y chromosome may be related with short stature.

PMID- 29658241
TI  - [Nursing care of prostate cancer patients against radiative proctitisinduced by
      CyberKnife treatment].
AB  - Objective: To investigate the nursing care of prostate cancer (PCa) patients
      againstradioactive proctitisinduced byCyberKnifetreatment. METHODS: Sixty
      eightPCapatients undergoingCyberKnife treatment in the observation group
      receivedspecialnursing care againstradioactive proctitis. The nursing measures
      includedthoserelevant toCyberKnife treatment, prevention ofradioactive proctitis,
      skin care, and discharge guidance. Meanwhile, another 54 prostate cancer patients
      received traditional nursing care as controls. We compared the incidence rate and
      severity of radioactive proctitis between the two groups of patients. RESULTS:
      The incidence rate of radioactive proctitiswas markedly lower in the observation
      group than in the control (2.9% vs 13.0%, P<0.05), but no statistically
      significant difference was observed in the severity of radioactive proctitis
      between the two groups of patients. CONCLUSIONS: The special nursing care
      againstCyberKnife-induced radioactiveproctitiscan significantlyreduce the
      incidence of radioactive proctitis andimprove the effect of CyberKnife treatment
      of prostate cancer, which therefore deserves wide clinical application.

PMID- 29658242
TI  - [Transcutaneous electrical acupoint stimulation for asthenozoospermia].
AB  - Objective: To study the effect of transcutaneous electrical acupoint stimulation
      (TEAS) in the treatment of asthenozoospermia. METHODS: We randomly divided 72
      asthenozoospermia patients into a 2 Hz TEAS (n = 29), a 100 Hz TEAS (n = 20), and
      a blank control group (n = 23), those in the former two groups treated by 30
      minutes of TEAS at 2 Hz and 100 Hz respectively, applied to the acupoints of
      bilateral Shenshu, left Zusanli, and Guanyuan, once a day for 60 days, while
      those in the blank control group left untreated. Using computer-assisted sperm
      analysis (CASA), we examined sperm concentration and motility as well as the
      percentages of grade a and grade a+b sperm in different groups of the patients.
      RESULTS: Compared with the baseline, 2 Hz TEAS significantly increased sperm
      motility ([12.76 +/- 1.39] vs [18.89 +/- 2.46]%, P<0.05) and the percentage of
      grade a+b sperm ( [10.68 +/- 1.22] vs [16.32 +/- 2.10]%, P<0.05) in the
      asthenozoospermic patients, while 100 Hz TEAS improved not only sperm motility
      ([12.32 +/- 2.21] vs [23.81 +/- 3.42]%, P<0.01) and the percentage of grade a+b
      sperm ([10.45 +/- 1.98] vs [20.25 +/- 2.82 ]%, P<0.01), but also the percentage
      of grade a sperm ([6.44 +/- 1.16] vs [13.31 +/- 2.30]%, P<0.05). Moreover, in
      comparison with the blank control group, 2 Hz TEAS also remarkably increased
      sperm motility ([9.57 +/- 1.60] vs [18.89 +/- 2.46]%, P<0.05) and the percentage
      of grade a+b sperm ([7.81 +/- 1.31] vs [16.32 +/- 2.10]%, P<0.05) in the
      asthenozoosperma patients, while 100 Hz TEAS improved not only sperm motility
      ([9.57 +/- 1.60] vs [23.81 +/- 3.42]%, P<0.01) and the percentage of grade a+b
      sperm ([7.81 +/- 1.31] vs [20.25 +/- 2.82]%, P<0.01) but also the percentage of
      grade a sperm ([4.87 +/- 1.01] vs [13.31 +/- 2.30]%, P<0.01). Meanwhile, the rate
      of clinical effectiveness was significantly higher in the 100 Hz TEASthan in the
      blank control group either in intention-to-treat (ITT) analysis (100% vs 18.18%)
      orper-protocol (PP) analysis (90% vs 0%), and so was it than in the 2 Hz TEAS
      group based on the data of ITT (100% vs 33.33%). CONCLUSIONS: Both 2 Hz and 100
      Hz TEAS are effective for the treatment of asthenozoospermia by improving sperm
      motility and vitality.

PMID- 29658243
TI  - [Radium-223 for the treatment of bone metastasis of prostate cancer].
AB  - Over 80% of the patients with prostate cancer (PCa) develop bone metastasis,
      which seriously affects the patients' quality of life and remains a major cause
      of morbidity. Radium-223 (Ra-223), a newly approved agent targeting bone
      metastasis of PCa, can improve the quality of life and prolong the overall
      survival of the PCa patients with bone metastasis. This article presents an
      overview of the clinical trials recently published on the management of bone
      metastasis of PCa with Ra-223.

PMID- 29658244
TI  - [Advances in the studies of lipoic acid in male infertility].
AB  - Lipoic acid (LA) is widely present in the body as a disulfide compound with an
      extensive biological activity and a strong antioxidant capacity. LA plays an
      antioxidant role by removing oxygen free radicals, chelating metal ions, and
      regenerating other antioxidants in the body. Recent studies have shown the
      effects of LA in the prevention or treatment of male reproductive disorders, such
      as idiopathic oligoasthenozoospermia, diabetes mellitus-induced erectile
      dysfunction and infertility, serious infection in the reproductive system, and
      reproductive system injuries caused by chemotherapeutic agents, ionizing
      radiation, environmental toxins, testicular ischemia reperfusion, excessive
      exercise, and so on.

PMID- 29658245
TI  - [Treatment of erectile dysfunction in patients with spinal cord injury].
AB  - The majority of men with spinal cord injury (SCI) suffer from different types and
      degrees of erectile dysfunction (ED). The impact of SCL on erectile function
      depends on the severity and location of the injury. Some patients can restore the
      residual sexual potential in the period of SCI recovery. Treatments of ED in men
      with SCI include psychotherapy, medication of oral PDE5 inhibitors,
      intracavernous injection of vasoactive drugs, transurethral medication,
      application of the vacuum erectile device and penile ring, penile prostheses,
      sacral neuromodulation, etc., among which PDE5 inhibitors remain the first option
      and usually give good clinical results for those with higher SCI. However,
      intracavernous injection of vasoactive drugs and combined treatment are
      preferable for those with lower SCI.

PMID- 29658246
TI  - [Expression characteristics of the Daxx gene in the mouse testis during
      spermatogenesis].
AB  - Objective: To investigate the expression characteristic of the Daxx gene in the
      mouse testis and its role in spermatogenesis. METHODS: Real-time PCR, Western
      blot and immunofluorescence were used in examining the expression characteristics
      of DAXX in the testis tissue from wild-type, Sertoli cell-specific androgen
      receptor knockout (SCARKO) and androgen receptor knockout (ARKO) mice at
      different postnatal weeks . RESULTS: The Daxx gene was highly expressed in the
      testis tissue and mainly in the nuclei of the wild-type mice at 4 postnatal
      weeks. Compared with the wild-type, the ARKO mice showed a markedly decreased
      expression of DAXX (0.299+/-0.026), which displayed a polar distribution in the
      spermatogenic cells (0.853+/-0.058) and exhibited no significant difference in
      the SCARKO mice (1.000+/-0.015). CONCLUSIONS: The Daxx gene expression is the
      highest in the middle-stage development of the mouse testis, significantly
      decreased in ARKO mice as compared with the wild-type, and its location
      influenced by specific AR knockout in Sertoli cells. DAXX may be involved in the
      regulation of spermatogenesis in mice.

PMID- 29658247
TI  - [Lentiviral vectors carrying siRNA inhibit S1PR3 gene expression in the corpus
      cavernosum smooth muscle cells of rats with spontaneous hypertension].
AB  - Objective: To screen lentiviral vectors carrying siRNA which can specifically
      down-regulate the gene expression of the sphingosine-1-phosphate receptor 3
      (S1PR3) in the corpus cavernosum smooth muscle (CCSM) cells of rats with
      spontaneous hypertension (SHT) and investigate the influence of the vectors on
      the signaling pathways of ROCK1, ROCK2 and eNOS in the CCSM cells of SHT rats.
      METHODS: Using the S1PR3 mRNA sequence of the rat as an interfering target, we
      designed and synthesized three pairs of siRNA sequences (siRNA1, 2 and 3)
      targeting S1PR3 and one pair of negative control, and then constructed and
      packaged them into lentiviral vectors. We cultured the CCSM cells of SHT and
      Wistar-Kyoto (WKY) rats in vitro and randomly divided them into groups A (SHT
      untransfected control), B (SHT transfected and carrying negative control virus),
      C (SHT transfected and carrying siRNA1 targeting S1PR3), D (SHT transfected and
      carrying siRNA2 targeting S1PR3), E (SHT transfected and carrying siRNA3
      targeting S1PR3), and F (WKY untransfected control). With the multiplicity of
      infection (MOI) = 60, we transfected the CCSM cells of the SHT rats with the
      lentiviral vector and then determined the expression of the green fluorescent
      protein (GFP) as well as the mRNA and protein expressions of S1PR3, ROCK1, ROCK2
      and eNOS in the CCSM cells of the SHT and WKY rats by RT-PCR and Western blot.
      RESULTS: Gene sequencing proved the successful construction of the lentiviral
      vector. The transfection efficiency of the CCSM cells of the rats was >80% in
      groups B, C, D and E. Compared with group A, the mRNA and protein expressions of
      S1PR3, ROCK1 and ROCK2 exhibited no significant difference in group B but were
      remarkably decreased in groups C, D, E and F (P< 0.05), most significantly in
      group E, with the inhibition rates of the mRNA and protein expressions of S1PR3
      of (34.2+/-2.9) and (77.7+/-4.7)%, those of ROCK1 of (33.3+/-1.4) and (51.1+/
      7.3)%, and those of ROCK2 of (30.8+/-3.6) and (58.32+/-5.5)%, respectively. The
      mRNA and protein expressions of eNOS in group A showed no significant difference
      from those in groups B, C, D and E (P>0.05) but remarkably lower than those in
      group F (P< 0.05). Compared with group F, the mRNA and protein expressions of
      S1PR3, ROCK1 and ROCK2 were not significantly different from those in group E
      (P>0.05) but markedly increased in groups A, B, C and D (P< 0.05), while those of
      eNOS remarkably decreased in groups A, B, C, D and E (P< 0.05). CONCLUSIONS: The
      three constructed lentiviral vectors carrying siRNA targeting different loci of
      the S1PR3 gene could significantly inhibit the expression of S1P3 as well as
      RhoA/Rho kinase signaling pathways in the CCSM cells of SHT rats, and the vector
      carrying siRNA3 exhibited the highest inhibitory effect.

PMID- 29658248
TI  - [Expression of long non-coding RNA H19 in prostate cancer and its effect on the
      proliferation and glycometabolism of human prostate cancer cells].
AB  - Objective: To study the expression of long non?coding RNA (lncRNA) H19 in human
      prostate cancer tissue and its effect on the glycometabolism and growth of human
      prostate cancer cells. METHODS: Real?time quantitative RT?PCR (qRT?PCR) was
      employed to detect the expression of lncRNA H19 in human prostate tissues from 20
      patients with prostate cancer (10 cases of high?Gleason score prostate cancer
      [HGPC] and 10 cases of low?Gleason score prostate cancer [LGPC]) and another 5
      with benign prostatic hyperplasia (BPH). After transfection of H19 siRNA into the
      DU145 and PC?3 prostate cancer cells, the growth of the cells and the H19
      expression in the cells were determined by MTT and qRT?PCR respectively, and the
      changes in the glycometabolism of the prostate cancer cells were analyzed by
      measuring the contents of glucose and lactate in the culture medium.
      Non?transfected and transfected negative vectors were used as blank and negative
      controls respectively. RESULTS: The relative expression of H19 was significantly
      increased in both the HGPC and LGPC tissues (0.725+/-0.385 and 2.086+/-0.542) as
      compared with that in the BPH tissue (0.210+/-0.068) (P< 0.01), even higher in
      the HGPC than in the LGPC tissue (P< 0.01). After transfection of H19 siRNA, the
      expressions of H19 were remarkably decreased in the DU145 and PC?3 prostate
      cancer cells in comparison with those in the blank control and negative control
      groups (P< 0.01), and so were the proliferation of and the glucose and lactate
      levels in the DU145 and PC?3 cells (P< 0.01).

PMID- 29658249
TI  - [Vasectomy has no obvious long?term influence on the levels of serum androgens in
      aging males].
AB  - Objective: To explore the long?term influence of vasectomy on the levels of serum
      androgens in aging males. METHODS: Using stratified random sampling, we conducted
      a questionnaire survey and physical examinations among 437 adult males aged >=40
      years, 232 with and 205 without the history of vasectomy. In addition, we
      measured the levels of serum total testosterone (TT), sex?hormone binding
      globulin (SHBG), calculated free testosterone (cFT), testosterone secreting index
      (TSI), free testosterone index (FTI), and luteinizing hormone (LH). RESULTS:
      Compared with the non?vasectomy group, the vasectomy group showed significantly
      increased levels of serum TT ([16.01+/-5.41] vs [17.39+/-6.57] nmol/L), SHBG
      ([58.91+/-36.89] vs [70.28+/-40.90] nmol/L), and LH ([8.86+/-6.49] vs [10.85+/
      11.73] IU/L) (all P< 0.05) and a decreased level of FTI (0.33+/-0.15 vs 0.30+/
      0.12, P< 0.05). There were no statistically significant differences between the
      non?vasectomy and vasectomy groups in cFT ([0.24+/-0.07] vs [0.23+/-0.09] nmol/L)
      or TSI ([2.42+/-1.34] vs [2.46+/-1.51] nmol/IU) (both P>0.05), nor after
      adjustment for relevant factors in TT (beta: 1.015, 95% CI: -0.180-2.210), SHBG
      (beta: 5.118, 95% CI: -2.069-12.305), cFT (beta: 0.003, 95% CI: -0.011-0.018),
      FTI (beta: -0.012, 95% CI: -0.035-0.011), TSI (beta: 0.138, 95% CI: -0.131
      0.407), and LH (beta: 1.011, 95% CI: -0.811-2.834) (all P>0.05). CONCLUSIONS:
      Vasectomy has no obvious long?term influence on the levels of serum androgens in
      aging males.

PMID- 29658250
TI  - [Dynamic changes of reproductive hormone levels and related factors in old and
      middle?aged men in health examination].
AB  - Objective: To investigate the dynamic changes of serum reproductive hormone
      levels in old and middle?aged males in health examination and their correlation
      with age and lipid profile. METHODS: This study included 4 333 men in health
      examination from January 2011 to December 2014. The men were aged from 40 to 85
      years old and divided into seven five?year?span age groups. We determined the
      levels of serum testosterone (T), luteinizing hormone (LH), follicle?stimulating
      hormone (FSH), estradiol (E2), progesterone (P), prolactin (PRL), total
      cholesterol (TC), triglyceride (TG), low?density lipoprotein cholesterol (LDL?C),
      high?density lipoprotein cholesterol (HDL?C), and the testosterone secretion
      index (TSI = T/LH). We analyzed the obtained data using SPSS Pram, Kruskal?Wallis
      H test, Mann?Whitney U test, exponential regression, and Spearman correlation
      analysis. RESULTS: Statistically significant differences were found in LH, FSH,
      E2 and TSI among the seven age groups (P< 0.05). The levels of serum LH, FSH and
      E2 were significantly higher (P< 0.05) while TSI remarkably lower (P< 0.05) in
      the >=70 yr group than in the other six groups. The serum T and E2 levels and TSI
      were markedly lower in the 40-44, 45-49 and 50-54 yr groups in 2014 than in the
      other three years (P< 0.05), and so were the levels of serum T and TSI in the 55
      59 yr group (P< 0.05). The levels of serum LH, FSH and E2 were correlated
      positively while those of P, PRL and TSI negatively with age. The serum T level
      was correlated positively with HDL?C but negatively with TC, TG and LDL?C. The
      levels of serum LH, FSH and E2 showed a yearly average increase of 1.9%, 2.7% and
      0.5%, respectively, while TSI an annual mean decline of 2.0% in the 40-85 yr
      group. CONCLUSIONS: LH, FSH and E2 were increased while TSI decreased with age in
      the >40 years old males. T and TSI were reduced in the 40-59 years old men from
      2011 to 2014, and so was E2 in the 40-54 yr group. Low?level testosterone is
      closely related to dyslipidemia.

PMID- 29658252
TI  - [Single nucleotide polymorphism of the TP53 gene is not correlated with male
      infertility].
AB  - Objective: To investigate the correlation of the single nucleotide polymorphism
      (SNP) rs1042522 of the tumor protein p53 (TP53) gene with the risk of male
      infertility. METHODS: This case?control study included 380 male patients with
      idiopathic infertility and 398 normal fertile men as controls from the Nanjing
      area. We genotyped the SNP rs1042522 of the TP53 gene by Sequence Mass Array and
      analyzed the correlation of the SNP with male infertility using the logistic
      regression model. RESULTS: Compared with the normal controls, the patients with
      idiopathic infertility showed significantly decreased sperm concentration
      ([77.34+/-49.24] vs [13.13+/-24.96] *106/ml), percentage of progressively motile
      sperm ([42.55+/-9.57] vs [10.38+/-5.57]%), serum testosterone level ([14.07+/
      5.36] vs [11.89+/-4.50] nmol/L), and follicle?stimulating hormone level ([16.80+/
      18.20] vs [4.55+/-7.17] U/L) (P < 0.05) but no statistically significant
      differences in other parameters. No correlation was observed between the SNP
      frequencies and male infertility and similar results were found in the subgroups
      of the cases. CONCLUSIONS: SNP rs1042522 of the TP53 gene is not significantly
      correlated with the risk of male infertility.

PMID- 29658251
TI  - [Nucleotide polymorphism rs4880 of the SOD2 gene and the risk of male
      infertility].
AB  - Objective: To investigate the correlation of the single nucleotide polymorphism
      (SNP) rs4880 of the superoxide dismutase 2 (SOD2) gene with the risk of male
      infertility. METHODS: This case?control study included 519 male patients with
      idiopathic infertility (aged 19-40 [28.93+/-4.93] years) in the case group and
      338 fertile men (aged 19-40 [28.40+/-4.25] years) in the control group. We
      collected the clinical data, genotyped the SNP rs4880 of the SOD2 gene by
      Sequenom Mass Array, and analyzed the association of different genotypes with
      male infertility using the logistic regression model. RESULTS: Statically
      significant differences were observed between the case and control groups in the
      level of follicle?stimulating hormone (FSH) ([4.72+/-2.51] vs [15.65+/-17.24]
      U/L, P< 0.01), the percentage of progressively mobile sperm ([9.12+/-13.5] vs
      [41.95+/-9.03]%, P< 0.01), and sperm concentration ([12.95+/-24.38] vs [72.88+/
      45.60] *106/ml, P< 0.01), but not in other parameters. No correlation was found
      between male infertility and the heterozygous genotype TC (OR = 0.90, 95% CI:
      0.65-1.25, P = 0.516) or the homozygous genotype CC (OR=1.49, 95% CI: 0.38-5.81,
      P = 0.566) as compared with the wild genotype TT, and similar results were
      obtained in the analysis of the subgroups. CONCLUSIONS: The SNP rs4880 of the
      SOD2 gene was not correlated with male infertility, which, however, is to be
      supported by further studies with larger samples from more areas.

PMID- 29658253
TI  - [Surgical treatment of advanced penile cancer without distant metastasis].
AB  - Objective: To investigate the effect of surgery on advanced penile cancer without
      distant metastasis and the factors influencing the prognosis. METHODS: Between
      September 2007 and July 2015, we treated 8 cases of advanced penile cancer
      without distant metastasis by penectomy and lymph node dissection. The patients
      were aged 37-67 (mean 51.1) years. We followed up the patients for 4-60 (mean
      19.25) months postoperatively and analyzed the surgical effects and the factors
      affecting the prognosis. RESULTS: Three of the patients remained alive while the
      other 5 (62.5%) died at 4-13 (mean 9) months after surgery. No significant
      complications were observed and myocutaneous flap repair showed good prognosis in
      4 of the patients with large?area skin defect. CONCLUSIONS: Surgery is
      comparatively a valuable option for the treatment of advanced penile cancer
      without distant metastasis, though with a poor prognosis, and the important
      factor affecting its prognosis is lymph node metastasis. Flap repair can solve
      the problem of large?area skin defect after surgery. However, evidence is not yet
      sufficient to prove the effectiveness of multimodality therapy of this
      malignancy.

PMID- 29658254
TI  - [Value of sperm acrosin activity detection in selecting the method of assisted
      reproduction for patients with unexplained infertility].
AB  - Objective: To investigate the clinical significance of sperm acrosin activity
      detection in selecting the method of assisted reproduction for patients with
      unexplained infertility (UI). METHODS: This retrospective study included 49 UI
      couples treated by IVF?ET (49 cycles) after three failures in intrauterine
      insemination (IUI) and another 95 couples with uterine tube obstruction (UTO)
      treated by IVF (131 cycles). We analyzed the laboratory data, clinical outcomes
      and sperm acrosin activity in the two groups of patients. According to the level
      of sperm acrosin activity of the males, we further divided the UI patients into
      two subgroups, a < 36 IU/106 sperm group (20 cycles) and a >=36 IU/106 sperm
      group (29 cycles), and compared the fertilization rates between the two groups.
      RESULTS: Compared with UI couples treated by IVF?ET, the UTO couples treated by
      IVF had a significantly lower rate of fertilization (67.0% vs 76.4%, P < 0.05)
      and a higher rate of remedial intracytoplasmic sperm injection (ICSI) (20.4% vs
      6.1%, P < 0.05), but showed no statistically significant differences in the rates
      of MII oocytes, available embryos, high?quality embryos, implantation, and
      clinical pregnancy from the latter group (P >0.05). The sperm acrosin activity
      was remarkably lower in the UI than in the UTO patients (36.03 vs 61.98 IU/106, P
      < 0.01), and so was the fertilization rate in the < 36 IU/106 than in the >=36
      IU/106 sperm subgroup (47.7% vs 80.3%, P < 0.01). CONCLUSIONS: The low
      fertilization rate caused by decreased sperm acrosin activity may be the main
      cause of infertility and the potential factor of UI. When sperm acrosin activity
      is < 36 IU/106 sperm, IVF plus short?term fertilization by remedial ICSI should
      be preferred to IUI.

PMID- 29658255
TI  - [Combination of musk and olibanum promotes proliferation of prostate stem cells
      in mice: An experimental study].
AB  - Objective: To study the effects of musk?olibanum combination on the proliferation
      and differentiation of prostate stem cells. METHODS: We cultured prostate
      epithelial cells and urogenital sinus mesenchymal (UGSM) cells from 7-10 d old
      C57BL/6 mice and 16-18 d old pregnant C57BL/6 mice, transplanted the mixed
      suspension of the two types of cells under the kidney envelope of SCIDCB.17 male
      mice, and harvested the transplants 30 days later. We randomly divided the
      SCIDCB.17 mice into four groups to be treated intragastrically with musk (n = 8),
      olibanum (n = 8), musk+olibanum (n = 7), and normal saline (blank control, n =
      8)) respectively, all for 14 days. Then we collected the kidney tissue for
      observation of the morphology of the glandular tubes and differentiation of
      different subsets of stem cells by HE staining and determination of the
      expressions and distribution of P63, CD133, CD117 and Sca?1 by
      immunohistochemistry and Western blot. RESULTS: A system was successfully
      established for the isolation and mixed culture of Sca?1 Lin?+ CD49f+ (LSC) cells
      of prostate stem cells and UGSM cells of the mouse embryonic prostate.
      Immunohistochemistry showed positive expressions of P63, CD133, Sca?1, and CD117
      in the prostatic acinar epithelia and proved the presence of prostatic acinar
      epithelial structure in the transplants. Compared with the blank control group,
      the expressions of CD133, Sca?1 and CD117 were significantly increased in the
      musk, olibanum, and musk+olibanum groups (P< 0.05), higher in the musk+olibanum
      than in the musk or olibanum group (P< 0.05), and their protein expressions were
      even more elevated in the musk+olibanum group (P< 0.01), with statistically
      significant difference from the olibanum group (P< 0.05). CONCLUSIONS: The
      combination of musk and olibanum can improve the proliferation and
      differentiation of prostate stem cells.

PMID- 29658256
TI  - [Bushen Daozhuo Granules for type III prostatitis: A multicenter randomized
      controlled clinical trial].
AB  - Objective: To study the safety and efficacy of Bushen Daozhuo Granules (BDG) in
      the treatment of type III prostatitis. METHODS: This multi?center randomized
      controlled clinical trial included 478 patients with type III prostatitis, 290 in
      the trial group and 188 as controls, the former treated with BDG at 200 ml bid
      and the latter with tamsulosin hydrochloride sustained?release capsules at 0.2 mg
      qd, both for 4 weeks. Before treatment, after 4 weeks of medication, and at 4
      weeks after drug withdrawal, we obtained the NIH Chronic Prostatitis Symptom
      Index (NIH?CPSI) scores and compared the safety and effectiveness rate between
      the two groups of patients. RESULTS: Compared with the baseline, the NIH?CPSI
      score was markedly decreased in the control group after 4 weeks of medication
      (21.42 +/- 4.02 vs 15.67 +/- 3.65, P < 0.05) but showed no statistically
      significant difference from that at 4 weeks after drug withdrawal (19.03 +/-
      3.86) (P>0.05), while the NIH?CPSI score in the trial group was remarkably lower
      than the baseline both after 4 weeks of medication and at 4 weeks after drug
      withdrawal (10.92 +/- 2.06 and 12.91 +/- 2.64 vs 21.58 +/- 3.67, P < 0.05). The
      trial group exhibited both a higher rate of total effectiveness and safety than
      the control (P < 0.05). CONCLUSIONS: BDG is safe and effective for the treatment
      of type III prostatitis.

PMID- 29658257
TI  - [Ningmitai Capsules combined with doxycycline hydrochloride for Ureaplasma
      urealyticum?positive chronic prostatitis].
AB  - Objective: To investigate the effects of Ningmitai Capsules (NMT) combined with
      doxycycline hydrochloride (DH) on chronic prostatitis induced by Ureaplasma
      urealyticum (Uu). METHODS: This randomized controlled trial included 240 male
      patients with Uu?positive chronic prostatitis, treated orally with NMT at 4
      capsules tid (n= 35), DH at 100 mg bid (n = 78), and NMT+DH at the corresponding
      doses (n = 127), respectively, all for 2 successive weeks. At 1 week after drug
      withdrawl, we conducted routine urine analysis, EPS examination, and drug
      sensitivity test of the cultured Uu. RESULTS: The positive?to?negative rate of Uu
      was significantly higher in the NMT+DH group than in the NMT and DH groups (89.0%
      [113/127] vs 54.3% [19/35] and 71.8% [56/78], P< 0.05), so were the cure rate
      (25.2% vs 20.0% and 20.5%, P< 0.05) and total effectiveness rate (89.0% vs 54.3%
      and 71.8%, P< 0.05). CONCLUSIONS: The combination of Ningmitai Capsules and
      doxycycline hydrochloride is more effective than either Ningmitai Capsules or
      doxycycline hydrochloride used alone in the treatment of Uu?positive chronic
      prostatitis.

PMID- 29658258
TI  - [Traditional Chinese medicine fumigation combined with Levofloxacin for type IIIA
      prostatitis with the symptoms of damp heat and blood stasis].
AB  - Objective: To investigate the clinical effects of traditional Chinese medicine
      (TCM) fumigation on type IIIA prostatitis with the symptoms of damp heat and
      blood stasis. METHODS: We randomly divided 72 cases of type IIIA prostatitis with
      the symptoms of damp heat and blood stasis into an experimental and a control
      group of equal number, the former treated with TCM fumigation plus oral
      Levofloxacin while the latter with oral Levofloxacin only. After 4 weeks of
      treatment, we compared the National Institute of Health Chronic Prostatitis
      Symptom Index (NIH?CPSI) score, TCM symptoms score, maxinum flow rate (Qmax), and
      average urinary flow rate (Qave) between the two groups of patients. RESULTS: The
      total effectiveness rate was significantly higher in the experimental than in the
      control group (91.7% vs 61.1%, P< 0.01), while the NIH?CPSI score in the
      experimental group was markedly decreased after treatment as compared with the
      baseline (14.5 +/- 8.2 vs 26.5 +/- 9.3, P< 0.05) and significantly lower than
      that in the control (14.5 +/- 8.2 vs 20.6 +/- 7.9, P< 0.05). Qmax was remarkably
      increased in the experimental group after treatment in comparison with the
      baseline ([21.2 +/- 4.3] vs [15.8 +/- 3.6] ml/s, P< 0.05) and the control group,
      and so was Qave as compared with pretreatment ([16.3 +/- 3.5] vs [10.5 +/- 2.8]
      ml/s, P< 0.05) and the control. However, the patients of the control group showed
      no statistically significant differences before and after treatment either in
      Qmax ([15.4 +/- 3.4] vs [16.1 +/- 2.9] ml/s, P>0.05) or in Qave ([10.9 +/- 2.4]
      vs [11.1 +/- 2.9] ml/s, P>0.05). CONCLUSIONS: TCM fumigation combined with
      Levofloxacin is an effective therapy for type IIIA prostatitis with the symptoms
      of damp heat and blood stasis, which can significantly improve the symptoms,
      reduce the NIH?CPSI score, and increase the Qmax and Qave of the patient.

PMID- 29658259
TI  - [Glycogen synthase kinase?3 and prostate cancer: An update].
AB  - Glycogen synthase kinase?3 (GSK?3alpha and GSK?3beta) are serine/threonine
      protein kinases acting on numerous substrates and involved in the regulation of
      various cellular functions such as their proliferation, survival, glycogen
      metabolism, and autophagy. Accumulating evidence indicates that the expression of
      GSK?3alpha is increased mainly in androgen?dependent while that of GSK?3beta in
      androgen?independent prostate cancer, and that GSK?3beta is also involved in the
      regulation of the transactivation of the androgen receptor (AR) and growth of
      prostate cancer. Animal experiments have proved that some GSK?3 inhibitors, such
      as lithium, can significantly suppress tumor growth in different animal models of
      prostate cancer. The GSK?3 inhibitor is promising to be an important agent for
      the clinical management of prostate cancer.

PMID- 29658260
TI  - [Impact of Mycoplasma and Chlamydia infections on male reproduction].
AB  - Infertility can be attributed to reproductive tract infections (RTI), most
      commonly non?gonococcal urethritis, mainly including Mycoplasma and Chlamydia
      infections, which may directly or indirectly damage spermatozoa and spermatogenic
      cells. In addition, a series of immune responses caused by such infections are
      also associated with male infertility. Methods for the clinical detection of
      these microbial infections are being constantly improved for more specific and
      precise control over the impact of Mycoplasma and Chlamydia infections on male
      fertility.

PMID- 29658261
TI  - Survivorship Care Preferences: A Pilot Study of Young Adults With Cancer
AB  - Background: Adolescents and young adults (AYAs) face increased risk for physical,
      social, and cognitive late complications of cancer therapy. Strategies are needed
      to better engage AYAs in survivorship research. Objectives: This study aimed to
      determine the feasibility of enrolling AYAs within six months of diagnosis to a
      survivorship study and assess their health concerns and survivorship care
      preferences. Methods: Patients aged 15-34 years who were diagnosed with leukemia,
      lymphoma, or sarcoma at three Connecticut hospitals from 2008-2011 were
      identified and recruited by mail. Participants and their physicians received a
      survivorship care plan. Participants completed surveys at 6 months and 18 months
      after diagnosis. Findings: Recruiting AYAs to survivorship research remains
      challenging, even when approaching them soon after diagnosis. Novel strategies
      are needed for nurses and other healthcare team members to engage AYAs in
      survivorship care and research.

PMID- 29658262
TI  - Novel Conductive Metal-Organic Framework for a High-Performance Lithium-Sulfur
      Battery Host: 2D Cu-Benzenehexathial (BHT).
AB  - Despite the high theoretical capacity of lithium-sulfur (Li-S) batteries, their
      commercialization is severely hindered by low cycle stability and low efficiency,
      stemming from the dissolution and diffusion of lithium polysulfides (LiPSs) in
      the electrolyte. In this study, we propose a novel two-dimensional conductive
      metal-organic framework, namely, Cu-benzenehexathial (BHT), as a promising sulfur
      host material for high-performance Li-S batteries. The conductivity of Cu-BHT
      eliminates the insulating nature of most S-based electrodes. The dissolution of
      LiPSs into the electrolyte is largely prevented by the strong interaction between
      Cu-BHT and LiPSs. In addition, orientated deposition of Li2S on Cu-BHT
      facilitates the kinetics of the LiPS redox reaction. Therefore, the use of Cu-BHT
      for Li-S battery cathodes is expected to suppress the LiPS shuttle effect and to
      improve the overall performance, which is ideal for practical application of Li-S
      batteries.

PMID- 29658264
TI  - Single Cell Titration-Type Assay for Plasma Membrane Cholesterol Chemical
      Potential.
AB  - In this paper, a titration-type assay is described that determines the minimum
      concentration of cholesterol in solution that is required to drive net influx of
      cholesterol to the plasma membrane and thus increase the cholesterol
      concentration. The increase in cholesterol in the plasma membrane is detected by
      cholesterol diffusion at the site of contact by a cholesterol oxidase-modified
      microelectrode. In the presented thermodynamic model, the minimum solution phase
      cholesterol concentration that drives influx to the plasma membrane is a close
      approximation of the true solution-phase equilibrium concentration of cholesterol
      produced from cellular cholesterol efflux and as such it is a quantitative
      measure of the chemical potential of cholesterol in the cellular plasma membrane.
      This assay provides a measure of cholesterol chemical potential in the living
      cellular plasma membrane through reference to a solution concentration which
      avoids invoking classic kinetic theory to relate a rate to a specific
      thermodynamic activity and which avoids uncertainty associated with mass transfer
      phenomena.

PMID- 29658263
TI  - Direct Correlations of Grain Boundary Potentials to Chemical States and
      Dielectric Properties of Doped CaCu3Ti4O12 Thin Films.
AB  - Colossal dielectric constant CaCu3Ti4O12 has been recognized as one of the rare
      materials having intrinsic interfacial polarization and thus unusual dielectric
      characteristics, in which the electrical state of the grain boundary is critical.
      Here, the direct correlation between the grain boundary potential and relative
      permittivity is proposed for the CaCu3Ti4O12 thin films doped with Zn, Ga, Mn,
      and Ag as characterized by Kelvin probe force microscopy. The dopants are
      intended to provide the examples of variable grain boundary potentials that are
      driven by chemical states including Cu+, Ti3+, and oxygen vacancy. Grain boundary
      potential is nearly linearly proportional to the dielectric constant. This effect
      is attributed to the increased charge accumulation near the grain boundary,
      depending on the choice of the dopant. As an example, 1 mol % Ag-doped
      CaCu3Ti4O12 thin films demonstrate the best relative permittivity as associated
      with a higher grain boundary potential of 120.3 mV compared with 82.6 mV for the
      reference film. The chemical states across grain boundaries were further verified
      by using spherical aberration-corrected scanning transmission electron microscopy
      with the simultaneous electron energy loss spectroscopy.

PMID- 29658265
TI  - Layer-by-Layer Assembly of Heparin and Peptide-Polyethylene Glycol Conjugates to
      Form Hybrid Nanothin Films of Biomatrices.
AB  - We investigated the utility of a heparin/peptide-polyethylene glycol conjugate
      system to build layer-by-layer (LbL) structures, to assemble tailored multilayer
      biomatrices for cell culture. The LbL assembly balances the advantages of
      polyelectrolyte systems and protein-based systems. Human umbilical vein
      endothelial cells showed distinct responses to the film thickness and structure;
      the presence, density, and spatial arrangement of a cell adhesion ligand within
      the nanothin film; and the pretreatment of the film with morphogens. The LbL
      technique presents a versatile tool for modifying cell culture substrates with
      defined and diverse biochemical and structural features, for investigating cell
      material interactions.

PMID- 29658266
TI  - Enzyme-Based Electrochemical Biosensor for Therapeutic Drug Monitoring of
      Anticancer Drug Irinotecan.
AB  - Therapeutic drug monitoring (TDM) is the clinical practice of measuring
      pharmaceutical drug concentrations in patients' biofluids at designated
      intervals, thus allowing a close and timely control of their dosage. To date, TDM
      in oncology can only be performed by trained personnel in centralized
      laboratories and core facilities employing conventional analytical techniques
      (e.g., MS). CPT-11 is an antineoplastic drug that inhibits topoisomerase type I,
      causing cell death, and is widely used in the treatment of colorectal cancer. CPT
      11 was also found to directly inhibit acetylcholine esterase (AChE), an enzyme
      involved in neuromuscular junction. In this work, we describe an enzymatic
      biosensor, based on AChE and choline oxidase (ChOx), which can quantify CPT-11.
      ACh (acetylcholine) substrate is converted to choline, which is subsequently
      metabolized by ChOx to give betaine aldehyde and hydrogen peroxide. The latter
      one is then oxidized at a suitably polarized platinum electrode, providing a
      current transient proportional to the amount of ACh. Such an enzymatic process is
      hampered by CPT-11. The biosensor showed a ~60% maximal inhibition toward AChE
      activity in the clinically relevant concentration range 10-10 000 ng/mL of CPT-11
      in both simple (phosphate buffer) and complex (fetal bovine serum) matrixes,
      while its metabolites showed negligible effects. These findings could open new
      routes toward a real-time TDM in oncology, thus improving the therapeutic
      treatments and lowering the related costs.

PMID- 29658267
TI  - Circular Dichroism Control of Tungsten Diselenide (WSe2) Atomic Layers with
      Plasmonic Metamolecules.
AB  - Controlling circularly polarized (CP) states of light is critical to the
      development of functional devices for key and emerging applications such as
      display technology and quantum communication, and the compact circular
      polarization-tunable photon source is one critical element to realize the
      applications in the chip-scale integrated system. The atomic layers of transition
      metal dichalcogenides (TMDCs) exhibit intrinsic CP emissions and are potential
      chiroptical materials for ultrathin CP photon sources. In this work, we
      demonstrated CP photon sources of TMDCs with device thicknesses approximately 50
      nm. CP photoluminescence from the atomic layers of tungsten diselenide (WSe2) was
      precisely controlled with chiral metamolecules (MMs), and the optical chirality
      of WSe2 was enhanced more than 4 times by integrating with the MMs. Both the
      enhanced and reversed circular dichroisms had been achieved. Through integrations
      of the novel gain material and plasmonic structure which are both low
      dimensional, a compact device capable of efficiently manipulating emissions of CP
      photon was realized. These ultrathin devices are suitable for important
      applications such as the optical information technology and chip-scale
      biosensing.

PMID- 29658268
TI  - Open-Source Potentiostat for Wireless Electrochemical Detection with Smartphones.
AB  - This paper describes the design and characterization of an open-source "universal
      wireless electrochemical detector" (UWED). This detector interfaces with a
      smartphone (or a tablet) using "Bluetooth Low Energy" protocol; the smartphone
      provides (i) a user interface for receiving the experimental parameters from the
      user and visualizing the result in real time, and (ii) a proxy for storing,
      processing, and transmitting the data and experimental protocols. This approach
      simplifies the design, and decreases both the size and the cost of the hardware;
      it also makes the UWED adaptable to different types of analyses by simple
      modification of the software. The UWED can perform the most common
      electroanalytical techniques of potentiometry, chronoamperometry, cyclic
      voltammetry, and square wave voltammetry, with results closely comparable to
      benchtop commercial potentiostats. Although the operating ranges of electrical
      current and voltage of the UWED (+/-1.5 V, +/-180 MUA) are more limited than most
      benchtop commercial potentiostats, its functional range is sufficient for most
      electrochemical analyses in aqueous solutions. Because the UWED is simple, small
      in size, assembled from inexpensive components, and completely wireless, it
      offers new opportunities for the development of affordable diagnostics, sensors,
      and wearable devices.

PMID- 29658269
TI  - Nonvolatile Control of Magnetocaloric Operating Temperature by Low Voltage.
AB  - The limited operating temperature is the main obstacle for the practical
      applications of magnetic refrigeration. In this work, the voltage control of
      magnetocaloric effect (MCE) is investigated in a La0.7Sr0.3MnO3 (LSMO)/CeO2/Pt
      device. Different from the conventional method of volatile manipulating MCE by
      large-voltage-induced strain, nonvolatile manipulation of magnetocaloric
      operating temperature with good stability is realized in the LSMO film by
      applying low voltages of less than 2.3 V. The experimental results demonstrate
      that the magnetic entropy change peak temperature for the LSMO film can be
      extended from 302 to 312 K by voltage. This nonvolatile effect can be well
      understood with the resistive switching mechanism and has potential in promoting
      microscale refrigeration technology.

PMID- 29658270
TI  - Dual-Mechanism and Multimotion Soft Actuators Based on Commercial Plastic Film.
AB  - Soft actuators have attracted a lot of attention owing to their biomimetic
      performance. However, the development of soft actuators that are easily prepared
      from readily available raw materials, conveniently utilized, and cost-efficient
      is still a challenge. Here, we present a simple method to fabricate a
      polyethylene-based soft actuator. It has controllable anisotropic structure and
      can realize multiple motions, including bidirectional bending and twisting based
      on dual mechanisms, which is a rare phenomenon. Especially, the soft actuators
      can response at a very small temperature difference (Delta T >= 2.3  degrees C);
      therefore, even skin touch can quickly drive the actuator, which greatly broadens
      its applications in daily life. The soft actuator could demonstrate a curvature
      up to 7.8 cm-1 accompanied by powerful actuation. We have shown that it can lift
      an object 27 times its own weight. We also demonstrate the application of this
      actuator as intelligent mechanical devices.

PMID- 29658271
TI  - Photosensitized Protein-Damaging Activity, Cytotoxicity, and Antitumor Effects of
      P(V)porphyrins Using Long-Wavelength Visible Light through Electron Transfer.
AB  - Photodynamic therapy (PDT) is a less-invasive treatment for cancer through the
      administration of less-toxic porphyrins and visible-light irradiation.
      Photosensitized damage of biomacromolecules through singlet oxygen (1O2)
      generation induces cancer cell death. However, a large quantity of porphyrin
      photosensitizer is required, and the treatment effect is restricted under a
      hypoxic cellular condition. Here we report the phototoxic activity of
      P(V)porphyrins: dichloroP(V)tetrakis(4-methoxyphenyl)porphyrin (CLP(V)TMPP),
      dimethoxyP(V)tetrakis(4-methoxyphenyl)porphyrin (MEP(V)TMPP), and
      diethyleneglycoxyP(V)tetrakis(4-methoxyphenyl)porphyrin (EGP(V)TMPP). These
      P(V)porphyrins damaged the tryptophan residue of human serum albumin (HSA) under
      the irradiation of long-wavelength visible light (>630 nm). This protein
      photodamage was barely inhibited by sodium azide, a quencher of 1O2. Fluorescence
      lifetimes of P(V)porphyrins with or without HSA and their redox potentials
      supported the electron-transfer-mediated oxidation of protein. The
      photocytotoxicity of these P(V)porphyrins to HeLa cells was also demonstrated.
      CLP(V)TMPP did not exhibit photocytotoxicity to HaCaT, a cultured human skin
      cell, and MEP(V)TMPP and EGP(V)TMPP did; however, cellular DNA damage was barely
      observed. In addition, a significant PDT effect of these P(V) porphyrins on a
      mouse tumor model comparable with the traditional photosensitizer was also
      demonstrated. These findings suggest the cancer selectivity of these
      P(V)porphyrins and lower carcinogenic risk to normal cells. Electron-transfer
      mediated oxidation of biomacromolecules by P(V)porphyrins using long-wavelength
      visible light should be advantageous for PDT of hypoxic tumor.

PMID- 29658272
TI  - Arsenite Targets the RING Finger Domain of Rbx1 E3 Ubiquitin Ligase to Inhibit
      Proteasome-Mediated Degradation of Nrf2.
AB  - Activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant
      response signaling pathway is a major mechanism for the cellular defense against
      oxidative stress. Arsenite, a widespread contaminant in drinking water, is known
      to induce oxidative stress and activate the Nrf2-dependent signaling pathway
      through the stabilization of the Nrf2 protein by inhibiting its ubiquitination
      via the Cul3-Rbx1-Keap1 (cullin 3, RING-box 1, and Kelch-like ECH-associated
      protein 1) E3 ubiquitin ligase, and its degradation by the 26S proteasome, though
      the underlying mechanism, remains elusive. In the present study, we demonstrated
      that arsenite could bind to the RING finger domain of Rbx1 in vitro and in cells,
      which led to the suppression of Cul3-Rbx1 E3 ubiquitin ligase activity, thereby
      impairing the Nrf2 ubiquitination and activating the Nrf2-induced antioxidant
      signaling pathway. Our finding provided novel insight into arsenic toxicity by
      uncovering a distinct mechanism accounting for arsenite-induced Nrf2 activation.

PMID- 29658274
TI  - Valley-Selective Exciton Bistability in a Suspended Monolayer Semiconductor.
AB  - We demonstrate robust optical bistability, the phenomenon of two well
      discriminated stable states depending upon the history of the optical input, in
      fully suspended monolayers of WSe2 at low temperatures near the exciton
      resonance. Optical bistability has been achieved under continuous-wave optical
      excitation that is red-detuned from the exciton resonance at an intensity level
      of 103 W/cm2. The observed bistability is originated from a photothermal
      mechanism, which provides both optical nonlinearity and passive feedback, two
      essential elements for optical bistability. The low thermal conductance of
      suspended samples is primarily responsible for the low excitation intensities
      required for optical bistability. Under a finite out-of-plane magnetic field, the
      exciton bistability becomes helicity dependent due to the exciton valley Zeeman
      effect, which enables repeatable switching of the sample reflectance by light
      polarization. Our study has opened up exciting opportunities in controlling light
      with light, including its wavelength, power, and polarization, using monolayer
      semiconductors.

PMID- 29658273
TI  - Dual Role of Humic Substances As Electron Donor and Shuttle for Dissimilatory
      Iron Reduction.
AB  - Dissimilatory iron-reducing bacteria (DIRB) are known to use humic substances
      (HS) as electron shuttles for dissimilatory iron reduction (DIR) by transferring
      electrons to HS-quinone moieties, which in turn rapidly reduce Fe(III) oxides.
      However, the potential for HS to serve as a source of organic carbon (OC) that
      can donate electrons for DIR is unknown. We studied whether humic acids (HA) and
      humins (HM) recovered from peat soil by sodium pyrophosphate extraction could
      serve as both electron shuttles and electron donors for DIR by freshwater
      sediment microorganisms. Both HA and HM served as electron shuttles in cultures
      amended with glucose. However, only HA served as an electron donor for DIR.
      Metagenomes from HA-containing cultures had an overrepresentation of genes
      involved in polysaccharide and to a lesser extent aromatic compound degradation,
      suggesting complex OC metabolism. Genomic searches for the porin-cytochrome
      complex involved in DIR resulted in matches to Ignavibacterium/Melioribacter,
      DIRB capable of polymeric OC metabolism. These results indicate that such taxa
      may have played a role in both DIR and decomposition of complex OC. Our results
      suggest that decomposition of HS coupled to DIR and other anaerobic pathways
      could play an important role in soil and sediment OC metabolism.

PMID- 29658275
TI  - Quantifying Reversible Surface Binding via Surface-Integrated Fluorescence
      Correlation Spectroscopy.
AB  - We present a simple and versatile single-molecule-based method for the accurate
      determination of binding rates to surfaces or surface bound receptors. To
      quantify the reversible surface attachment of fluorescently labeled molecules, we
      have modified previous schemes for fluorescence correlation spectroscopy with
      total internal reflection illumination (TIR-FCS) and camera-based detection. In
      contrast to most modern applications of TIR-FCS, we completely disregard spatial
      information in the lateral direction. Instead, we perform correlation analysis on
      a spatially integrated signal, effectively converting the illuminated surface
      area into the measurement volume. In addition to providing a high surface
      selectivity, our new approach resolves association and dissociation rates in
      equilibrium over a wide range of time scales. We chose the transient
      hybridization of fluorescently labeled single-stranded DNA to the complementary
      handles of surface-immobilized DNA origami structures as a reliable and well
      characterized test system. We varied the number of base pairs in the duplex,
      yielding different binding times in the range of hundreds of milliseconds to tens
      of seconds, allowing us to quantify the respective surface affinities and binding
      rates.

PMID- 29658276
TI  - Sous-Vide Nonenzymatic Browning of Glucosamine at Different Temperatures.
AB  - Sous-vide is an increasingly popular method of cooking under controlled
      conditions of temperature and time inside vacuumed pouches to preserve the
      nutritional and sensory qualities of food. Sous-vide nonenzymatic browning of
      glucosamine (GlcN) was investigated at 50, 60, and 70  degrees C for 12 h.
      Changes investigated were pH, color, level of browning, and the concentrations of
      the key Maillard and caramelization reaction products, including alpha
      dicarbonyls and pyrazines. The concentrations of undesired 4-methylimidazole (4
      MEI), 2-acetyl-4(5)-tetrahydroxybutyl imidazole (THI), and 5
      hydroxymethylfurfural (5-HMF) were also determined. Six types of caramels were
      produced of unique composition with no detectable levels of 4-MEI. GlcN caramels
      produced under vacuum were more acidic and lighter in color, containing
      significantly less flavorful diacetyl, but more fructosazine (FR) as compared to
      nonvacuum caramels. THI concentration was well below the toxicity levels for all
      studied caramels. Principal component analyses showed that the incubation
      temperature played a key role in determining the composition of caramels.

PMID- 29658278
TI  - Bioinspired Diastereoconvergent Synthesis of the Tricyclic Core of Palodesangrens
      via Diels-Alder Reaction, LiAlH4-Mediated Isomerization, and Acid-Mediated
      Cyclization.
AB  - The cyclohexene moiety of the tricyclic 6,7-diaryl-tetrahydro-6 H-benzo[
      c]chromene core of palodesangrens could be assembled in a biomimetic and step
      economical fashion by the Diels-Alder reaction between the electron-rich ( E)-1,3
      butadienylarenes as the diene and the electron-deficient chalcones as the
      dienophile. During the reduction of ketone to the corresponding alcohol by
      LiAlH4, the mixture of endo and exo isomers underwent a novel diastereoconvergent
      LiAlH4-mediated isomerization to install the desired stereochemistry at C10a.
      Subsequent pyran ring closure under acidic conditions installed the
      stereochemistry at the remaining C6. Overall, the tricyclic core of
      palodesangrens could be prepared in three steps and up to 38% yield.

PMID- 29658277
TI  - Cavitation Enhancement Increases the Efficiency and Consistency of Chromatin
      Fragmentation from Fixed Cells for Downstream Quantitative Applications.
AB  - One of the most sensitive, time-consuming, and variable steps of chromatin
      immunoprecipitation (ChIP) is chromatin sonication. Traditionally, this process
      can take hours to properly sonicate enough chromatin for multiple ChIP assays.
      Further, the length of sheared DNA is often inconsistent. In order to faithfully
      measure chemical and structural changes at the chromatin level, sonication needs
      to be reliable. Thus, chromatin fragmentation by sonication represents a
      significant bottleneck to downstream quantitative analysis. To improve the
      consistency and efficiency of chromatin sonication, we developed and tested a
      cavitation enhancing reagent based on sonically active nanodroplets. Here, we
      show that nanodroplets increase sonication efficiency by 16-fold and provide more
      consistent levels of chromatin fragmentation. Using the previously characterized
      chromatin in vivo assay (CiA) platform, we generated two distinct chromatin
      states in order to test nanodroplet-assisted sonication sensitivity in measuring
      post-translational chromatin marks. By comparing euchromatin to chemically
      induced heterochromatin at the same CiA:Oct4 locus, we quantitatively measure the
      capability of our new sonication technique to resolve differences in chromatin
      structure. We confirm that nanodroplet-assisted sonication results are
      indistinguishable from those of samples processed with traditional sonication in
      downstream applications. While the processing time for each sample was reduced
      from 38.4 to 2.3 min, DNA fragment distribution sizes were significantly more
      consistent with a coefficient of variation 2.7 times lower for samples sonicated
      in the presence of nanodroplets. In conclusion, sonication utilizing the
      nanodroplet cavitation enhancement reagent drastically reduces the amount of
      processing time and provides consistently fragmented chromatin of high quality
      for downstream applications.

PMID- 29658279
TI  - [The professional and family characteristics, difficulties, contentment and
      resources of physicians working at level 3 neonatal intensive care centres.
      General overview in Hungary].
AB  - INTRODUCTION: A survey that investigates the situation of physicians working at
      neonatal intensive care (NIC) centres has not been made since 1997. AIM: To give
      an overview of the sociodemographic characteristics; personal and professional
      problems; the satisfaction with their job and family roles; their levels of
      healthy lifestyle; resources in the families of physicians working at NIC.
      METHOD: We have made an examination in Hungary at NIC among physicians from April
      2015 till January 2016, with an anonym self-fill-in questionnaire. RESULTS: The
      physicians involved in the research (n = 111) are representatively middle-aged
      people. They are well-qualified and hold a subordinate post. Most of them have
      second jobs. The manager and deputy-manager positions are characteristic for the
      men. Most of them live in family. The main problems for them are financial and
      professional difficulties, not the family or personal problems. They have
      conflicts in families because of finding partners and having children as well as
      job problems. They are satisfied with their parenting, partnership and
      professional roles but they are not contented with their family role as a
      financial safety provider person and as a person living a healthy life. In
      difficult situations in their life, they can count on friends and family members,
      furthermore they can rely on their workmates and superiors. CONCLUSION: It is the
      first research that focuses on the general situation of physicians working at
      level 3 NIC centres. This is the first time when a survey investigates their
      professional-personal-family life. Orv Hetil. 2018; 159(16): 628-635.

PMID- 29658280
TI  - [Randomized, controlled clinical trials with observational follow-up
      investigations for evaluating efficacy of antihyperglycaemic treatment. II.
      Features of and lessons from the follow-up investigations].
AB  - Although the outcomes of the follow-up investigation period of the randomized
      clinical studies for evaluating the efficacy of a treatment or an antidiabetic
      drug may be confounded or potentially biased by several factors, the results are
      widely accepted by the diabetes community. In line with the theory of metabolic
      memory or metabolic legacy, early and intensive antihyperglycaemic treatment
      should be provided for all diabetic patients as this strategy can result in
      beneficial effects even in the long run. The recent cardiovascular safety trials
      with new, innovative antidiabetic drugs differ in several aspects from the former
      efficacy studies. Ten cardiovascular safety trials were completed so far enabling
      to define their unique and common features. It can be anticipated that the era of
      randomized, controlled efficacy studies with observational follow-up
      investigations came to an end in diabetes research. Nowadays, cardiovascular
      safety trials are in the focus of clinical research in diabetology and results of
      several ongoing studies are expected with interest in the near future. Orv Hetil.
      2018; 159(16): 615-619.

PMID- 29658281
TI  - [Treatment of metastatic progression following the synchronous occurrence of
      cutaneous and ocular primary melanomas].
AB  - The incidence rates of cutaneous melanoma in non-Hispanic whites show an
      increasing tendency with age. While uveal melanoma in general is a rare disease,
      representing only 4% of all melanomas with an incidence rate of 0.6 per 100 000,
      it is still the most frequent malignancy of the eye. Synchronous occurrence of
      ocular and cutaneous melanoma is an exceptional rarity, due to the distinct
      genetic background of the diseases. We report the case of a 80-year-old man who
      underwent total excision of a cutaneous melanoma in 2008. In 2013, he was
      diagnosed with uveal melanoma as part of a routine work-up for reduced vision.
      The uveal melanoma was treated by brachytherapy. In 2015, liver metastases were
      suspected by routine ultrasonography. Core biopsy was carried out, and the
      histology confirmed melanoma metastases. The molecular analysis of the cutaneous
      lesion showed gain of function mutation of the BRAF V600 K gene, while we found a
      wild-type BRAF gene in the metastatic lesion. Based on the recommendation of the
      oncoteam, hepatic intra-arterial Epirubicin-Platidiam therapy was introduced. He
      received 11 doses of intra-arterial chemotherapy (IAC), in 21 cycles. IAC was
      well tolerated without any catheter-related complications or toxicities. Partial
      regression of the hepatic metastases were documented in February 2016. After
      completing the eleventh cycle of intrahepatic chemotherapy, the disease remained
      in complete remission for over a year. The parallel occurrence of cutaneous and
      ocular melanoma is rare, however, the metastatic progression in such cases make
      the selection of optimal medical therapy challenging. The distinct genetic
      background of two melanoma types may help the identification of the source of the
      metastatic lesions, in order to guide the treatment decisions. Orv Hetil. 2018;
      159(16): 642-647.

PMID- 29658284
TI  - [Jozsef Honti MD would be 80].

PMID- 29658283
TI  - [Oligo- and polysacharides, proteoglycans].
AB  - After clearing up the confusion in the previously used nomenclature, the paper
      discusses the family of small-leucin-rich glycoproteins. After mentioning the
      family and its role in the organisation of the ground substance and in the
      regulation of inflammation, one unique molecule of proteoglycans is presented.
      This molecule is the inter-alpha-trypsin inhibitor. It has turned out that this
      peculiar molecule originally contains glycosaminoglycan beside the neutral
      carbohydrates. After summarizing the numerous connections of the proteoglycan
      molecule, the "self-sacrificing" nature of the molecule is presented. It is noted
      that the functions of the ovaries are also controlled by this molecule. The
      unique structure and fundamental function of the CD44 is also analysed. The CD44
      is a transmembrane proteoglycan receptor with diverse functions and actions. The
      organisation has intramolecular, transmembrane sections, a stalk and one globular
      part and contains glycosaminoglycan and oligosacharids, too. The construction
      contains sialic acid residues at end positions of the molecular chains, which
      hinder it from joining other sialic acid structures in terminal positions.
      Therefore, this molecule has to be separated to open up a way for the sequencing
      neutral molecule (e.g., hyaluronan) to be attached. CD44 is the most important,
      but not the only receptor of hyaluronan. It can form connections with a lot of
      constructions, e.g., blood cells, the human endothelial, adventitial and
      mesenchymal. Human extracellular matrix proteinases can change the receptor's
      structures. Both the molecular and the supramolecular complexes boast unique
      features. The giant hyaluronan chains can connect to hyaluronan-binding
      proteoglycans - particularly hyaladherins to hyaluronectins - to create
      supramolecular connections and networks. The molecular mass of the fragments of
      hyaluronan is in the range of some kDs, while the whole molecule weighs up to
      several million Ds. The fragments are independent masses and can form attachments
      by themselves. The fragments have important inflammatory effects. Previously
      unidentified proteoglycan fragments have also been identified. Five of the ten
      identified fragments are secreted after synthetizing and stored in the granula of
      human cells. These strange characteristics are connected to the features of
      chromogranins/secretogranins. Nevertheless, this is another system of the
      organism, the functional, molecular structures of which are synthetized in
      neuroendocrine cells. Orv Hetil. 2018; 159(16): 620-627.

PMID- 29658286
TI  - Personal Health Coaching as a Type 2 Diabetes Mellitus Self-Management Strategy:
      A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
AB  - OBJECTIVE: Personal health coaching (PHC) programs have become increasingly
      utilized as a type 2 diabetes mellitus (T2DM) self-management intervention
      strategy. This article evaluates the impact of PHC programs on glycemic
      management and related psychological outcomes. DATA SOURCES: Electronic databases
      (CINAHL, MEDLINE, PubMed, PsycINFO, and Web of Science). STUDY INCLUSION AND
      EXCLUSION CRITERIA: Randomized controlled trials (RCT) published between January
      1990 and September 2017 and focused on the effectiveness of PHC interventions in
      adults with T2DM. DATA EXTRACTION: Using prespecified format guided by the
      Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework.
      DATA SYNTHESIS: Quantitative synthesis for primary (ie, hemoglobin A1c [HbA1c])
      and qualitative synthesis for selected psychological outcomes. RESULTS: Meta
      analyses of 22 selected publications showed PHC interventions favorably impact
      HbA1c levels in studies with follow-ups at <=3 months (-0.32% [95% confidence
      interval, CI = -0.55 to -0.09%]), 4 to 6 months (-0.50% [95% CI = -0.65 to 
      0.35%], 7 to 9 months (-0.66% [95% CI = -1.04 to -0.28%]), and 12 to 18 months (
      0.24% [95% CI = -0.38 to -0.10%]). Subsequent subgroup analyses led to no
      conclusive patterns, except for greater magnitude of effect size in studies with
      conventional (2-arm) RCT design. CONCLUSIONS: The PHC appears effective in
      improving glycemic control. Further research is required to assess the
      effectiveness of specific program components, training, and supervision
      approaches and to determine the cost-effectiveness of PHC interventions.

PMID- 29658285
TI  - [Quality of life of patients with Raynaud's disease].
AB  - INTRODUCTION: Raynaud's disease is characterized by episodic vasospastic attacks
      and digital ischemia usually followed by pain, numbness and cold. Despite the
      severity of the symptoms, the investigation of the quality of life in this
      disease received less attention yet. AIM: The aim of the study was to examine how
      the disease affects the patients' quality of life. METHOD: Semi-structured
      interviews were made with 28 patients diagnosed with Raynaud's disease. RESULTS:
      Almost every domain of quality of life is negatively affected. The somatic
      symptoms cause significant suffering, they are accompanied by loss of
      functionality; frequent preventive actions are needed; furthermore they affect
      job performance, commuting and sleep quality. Emotional and cognitive burdens and
      negative changes in interpersonal relationships were found. CONCLUSION: The
      findings of this study show that the disease is present as significant hardship
      in every aspect of daily life. Because of the decrease in the quality of life and
      the psychological burdens caused by this chronic disease, not only the basic
      medical care, but psychological treatment is also indicated. Orv Hetil. 2018;
      159(16): 636-641.

PMID- 29658287
TI  - Perspectives on Providing And Receiving Preventive Health Care From Primary Care
      Providers and Their Patients With Mental Illnesses.
AB  - PURPOSE:: Individuals with mental illnesses have higher morbidity rates and
      reduced life expectancy compared to the general population. Understanding how
      patients and providers perceive the need for prevention, as well as the barriers
      and beliefs that may contribute to insufficient care, are important for improving
      service delivery tailored to this population. DESIGN:: Cross-sectional; mixed
      methods. SETTING:: An integrated health system and a network of federally
      qualified health centers and safety net clinics. PARTICIPANTS:: Interviews (n =
      30) and surveys (n = 249) with primary care providers. Interviews (n = 158) and
      surveys (n = 160) with patients diagnosed with schizophrenia, bipolar, anxiety,
      or major depressive disorders. MEASURES:: Semi-structured interviews and surveys.
      ANALYSIS:: Thematic analysis for qualitative data; frequencies for quantitative
      data. RESULTS:: More than half (n = 131, 53%) of clinicians believed patients
      with mental illnesses care less about preventive care than the general
      population, yet 88% (n = 139) of patients reported interest in improving health.
      Most providers (n = 216, 88%) lacked confidence that patients with mental
      illnesses would follow preventive recommendations; 82% (n = 129) of patients
      reported they would try to change lifestyles if their doctor recommended.
      Clinicians explained that their perception of patients' chaotic lives and lack of
      interest in preventive care contributed to their fatalistic attitudes on care
      delivery to this population. Clinicians and patients agreed on substantial need
      for additional support for behavior changes. Clinicians reported providing
      informational support by keeping messages simple; patients reported a desire for
      more detailed information on reasons to complete preventive care. Patients also
      detailed the need for assistive and tangible support to manage behavioral health
      changes. CONCLUSIONS:: Our results suggest a few clinical changes could help
      patients complete preventive care recommendations and improve health behaviors:
      improving clinician-patient collaboration on realistic goal setting, increasing
      visit time or utilizing behavioral health consultants that bridge primary and
      specialty mental health care, and increasing educational and tangible patient
      support services.

PMID- 29658288
TI  - Canadian Nutrition Society: Scientific Abstracts from the 9th Annual Scientific
      Meeting / Societe canadienne de nutrition : Resumes scientifiques de la 9e
      reunion scientifique annuelle.

PMID- 29658289
TI  - Cancer risk following alpha-emitter exposure.
AB  - The International Commission on Radiological Protection (ICRP) mandated a task
      group (Task Group 64) to review recently published epidemiological studies
      related to cancer risk and incorporated alpha emitters, and to evaluate whether
      the results might consolidate or challenge assumptions underlying the current
      radiation protection system. Three major alpha emitters were considered: radon
      and its decay products, plutonium, and uranium. Results came mainly from cohorts
      of workers, while for radon, major studies of the general population contributed
      to a better understanding of the risk of lung cancer at low and chronic exposure.
      Selection criteria for the review were: assessment of individual exposure of the
      target organ, long duration of the health survey, availability of attained age at
      end of follow-up, and adjustment for major co-factors. Task Group 64 is composed
      of members from ICRP Committees 1 and 2 (because epidemiological and dosimetric
      expertise were needed) and external experts. A first report (ICRP Publication
      115) considered the risk of lung cancer related to inhalation of radon and its
      decay products. As the estimated excess risk per unit of exposure was higher by a
      factor of 2 compared with a previous ICRP estimate in 1993, Task Group 64
      suggested a reconsideration of the reference levels for the workplace and for the
      general population. A second report, using the same standardised methodology
      (lung cancer baselines, population, life expectancy), will include estimation of
      the cancer risk of nuclear workers exposed to plutonium, focusing on the risk of
      lung cancer. A comparison of these risks with those of populations exposed to
      external gamma radiation alone will be made in the near future. For uranium, the
      results related to the organ-specific dose were too sparse to draw reliable
      conclusions, despite a recent publication. More research is needed on this topic.

PMID- 29658290
TI  - Dietary restriction slightly affects glucose homeostasis and delays plasma
      cholesterol removal in rabbits with dietary lipid lowering.
AB  - Dietary restriction (DR) has been reported to have beneficial effects on
      atherosclerotic progression as well as lipid and glucose metabolism, but little
      is known about whether these effects can be enhanced or weakened by dietary lipid
      lowering. Here, after 12 weeks of high-cholesterol diet feeding,
      hypercholesterolemic rabbits were fed with either a standard chow diet ad libitum
      (AL) or a standard chow diet with DR for 16 weeks of dietary lipid lowering. We
      found that the DR group exhibited a loss of body weight, smaller internal organs,
      and reduced fat mass, while the AL group accumulated more subcutaneous fat than
      the baseline group. DR treatment slightly worsened glucose tolerance but enhanced
      insulin sensitivity, and a slight effect of DR on insulin secretion was also
      observed. After dietary cholesterol withdrawal, rabbits showed persistent
      lowering of total cholesterol and triglycerides in plasma. However, the DR group
      had significantly higher plasma total cholesterol than the AL group at most time
      points during weeks 7 to 16 of lipid lowering. Although both the AL and DR groups
      developed more severe atherosclerosis than the baseline group, DR did not improve
      atherosclerotic progression or the accumulation of macrophages and smooth muscle
      cells. We conclude that DR affected glucose and lipid metabolism but did not
      ameliorate atherosclerosis in rabbits when associated with lipid lowering by
      dietary cholesterol withdrawal.

PMID- 29658292
TI  - Editorial.

PMID- 29658293
TI  - Corrigendum.
AB  - Corrigendum to ICRP Publication 128: Radiation dose to patients from
      radiopharmaceuticals: a compendium of current information related to frequently
      used substances. [Ann. ICRP 44(2S), 2015]. DOI: 10.1177/0146645314558019 . The
      following error has been identified in Table C.109, p. 280: The value of the
      absorbed dose per unit activity administered to the urinary bladder wall for the
      1-year-old child after oral administration of 131I-iodide should be 1.3E+00 mGy
      MBq-1, not 1.3E-01 as was originally stated. ICRP apologises for any
      inconvenience or confusion caused by this error.

PMID- 29658291
TI  - Teaching the Concepts of Quality Improvement for Challenging Patient Populations.

PMID- 29658294
TI  - ICRP Task Group 95: internal dose coefficients.
AB  - Internal doses are calculated using biokinetic and dosimetric models. These
      models describe the behaviour of the radionuclides after ingestion, inhalation,
      and absorption to the blood, and the absorption of the energy resulting from
      their nuclear transformations. The International Commission on Radiological
      Protection (ICRP) develops such models and applies them to provide dose
      coefficients and bioassay functions for the calculation of equivalent or
      effective dose from knowledge of intakes and/or measurements of activity in
      bioassay samples. Over the past few years, ICRP has devoted a considerable amount
      of effort to the revision and improvement of models to make them more
      physiologically realistic representations of uptake and retention in organs and
      tissues, and of excretion. Provision of new biokinetic models, dose coefficients,
      monitoring methods, and bioassay data is the responsibility of Committee 2 and
      its task groups. Three publications in a series of documents replacing the ICRP
      Publication 30 series and ICRP Publications 54, 68, and 78 have been issued
      [Occupational Intakes of Radionuclides (OIR) Parts 1-3]. OIR Part 1 describes the
      assessment of internal occupational exposure to radionuclides, biokinetic and
      dosimetric models, methods of individual and workplace monitoring, and general
      aspects of retrospective dose assessment. OIR Parts 2-5 provide data on
      individual elements and their radioisotopes. Work is also in progress on revision
      of dose coefficients for radionuclide intakes by members of the public.

PMID- 29658295
TI  - An Assessment of the Impact of Just Culture on Quality and Safety in US
      Hospitals.
AB  - In pursuit of high reliability, numerous organizations have promoted Just
      Culture, but its impact has never been assessed. This report combines data from a
      longitudinal survey-based study of clinical peer review practices in a cohort of
      457 acute care hospitals with 43 measures from the Hospital Compare database and
      interprets them in relation to the long-term trends of Agency for Healthcare
      Research and Quality (AHRQ) data on the Hospital Survey of Patient Safety
      Culture. In all, 211 of 270 respondents (79%) indicated that their hospital has
      adopted Just Culture. More than half believe that it has had a positive impact.
      Just Culture implementation and its degree of impact are associated with somewhat
      better peer review process, but not with objective measures of hospital
      performance. Non-Punitive Response to Error has consistently been the lowest
      scoring category (45% positive) in the AHRQ database. Widespread adoption of Just
      Culture has not reduced reluctance to report or the culture of blame it targets.

PMID- 29658296
TI  - Medical and health surveillance in postaccident recovery: experience after
      Fukushima.
AB  - The accident at Fukushima Daiichi nuclear power plant occurred following the huge
      tsunami and earthquake of 11 March 2011. After the accident, there was
      considerable uncertainty and concern about the health effects of radiation. In
      this difficult situation, emergency responses, including large-scale evacuation,
      were implemented. The Fukushima Health Management Survey (FHMS) was initiated 3
      months after the accident. The primary purposes of FHMS were to monitor the long
      term health of residents, promote their well-being, and monitor any health
      effects related to long-term, low-dose radiation exposure. Despite the severity
      of the Fukushima accident and the huge impact of the natural disaster, radiation
      exposure of the public was very low. However, there were other serious health
      problems, including deaths during evacuation, increased mortality among displaced
      elderly people, mental health and lifestyle-related health problems, and social
      issues after the accident. The Nuclear Emergency Situations - Improvement of
      Medical and Health Surveillance (SHAMISEN) project, funded by the Open Project
      For European Radiation Research Area, aimed to develop recommendations for
      medical and health surveillance of populations affected by previous and future
      radiation accidents. This paper briefly introduces the points that have been
      learned from the Fukushima accident from the perspective of SHAMISEN
      recommendations.

PMID- 29658297
TI  - Numerical investigation of bone remodelling around immediately loaded dental
      implants using sika deer (Cervus nippon) antlers as implant bed.
AB  - This study combines finite element method and animal studies, aiming to
      investigate tissue remodelling processes around dental implants inserted into
      sika deer antler and to develop an alternative animal consuming model for
      studying bone remodelling around implants. Implants were inserted in the antlers
      and loaded immediately via a self-developed loading device. After 3, 4, 5 and 6
      weeks, implants and surrounding tissue were taken out. Specimens were scanned by
      MUCT scanner and finite element models were generated. Immediate loading and
      osseointegration conditions were simulated at the implant-tissue interface. A
      vertical force of 10 N was applied on the implant. During the healing time,
      density and Young's modulus of antler tissue around the implant increased
      significantly. For each time point, the values of displacement, stresses and
      strains in the osseointegration model were lower than those of the immediate
      loading model. As the healing time increased, the displacement of implants was
      reduced. The 3-week immediate loading model (9878 +/- 1965 MUstrain) illustrated
      the highest strains in the antler tissue. Antler tissue showed similar
      biomechanical properties as human bone in investigating the bone remodelling
      around implants, therefore the use of sika deer antler model is a promising
      alternative in implant biomechanical studies.

PMID- 29658298
TI  - Anti-inflammatory lupane triterpenoids from Menyanthes trifoliata.
AB  - A new lupane triterpenoid, 23-O-trans-feruloylcylicodiscic acid (1), as well as
      four known analogues (2-5), was isolated from the EtOAc fraction of Menyanthes
      trefoliata. The structure of compound 1 was elucidated on the basis of extensive
      spectroscopic analysis, including 2D NMR data. The structures of the known
      compounds were established by comparison of their spectroscopic data with that in
      the literature. Compounds 1, 2, and 4 exhibited certain anti-NO production
      activities.

PMID- 29658299
TI  - Early to bed and early to rise makes a patient healthy, a hospital wealthy, and a
      doctor wise, or not?

PMID- 29658300
TI  - Professional ethics, mental health and dangerous decisions - reducing the risk of
      dangerousness in world leaders.

PMID- 29658301
TI  - Avoiding Pitfalls of Tibiotalocalcaneal Nail Malposition With Internal Rotation
      Axial Heel View.
AB  - BACKGROUND: Tibiotalocalcaneal (TTC) nails are often used for complex hind foot
      arthrodesis and deformity correction. The natural valgus alignment of the
      hindfoot creates a challenge to optimum placement of the guidewire and eventual
      nail with a straight or valgus-curved nail. METHODS: Five fresh frozen cadavers
      were used for placement of a TTC guidewire with standard anterior-posterior (AP),
      lateral, and Harris axial heel views as a reference for proper placement. The
      limb was then rotated 15 degrees , 30 degrees , and 45 degrees  both internally
      and externally to evaluate the perceived amount of osseous purchase within the
      calcaneus. The TTC nail was then inserted and dissection was performed to
      demonstrate proximity of the nail to the sustentaculum tali and neurovascular
      structures. RESULTS: A 30 degrees  internal rotation Harris axial heel view
      demonstrated the most accurate representation of osseous purchase within the
      calcaneus with the guidewire and nail placement. When the guidewire was placed
      with standard imaging the nail was often ultimately placed in close proximity to
      the sustentaculum tali and neurovascular structures. CONCLUSION: Careful
      placement of the guidewire prior to reaming and nail placement should be
      undertaken to avoid neurovascular injury and to increase osseous purchase. For
      optimal guidewire placement, the authors suggest using appropriate anatomic
      landmarks and using a 30 degrees  internally rotated Harris axial heel view to
      verify correct placement. LEVELS OF EVIDENCE: Level V: Expert opinion.

PMID- 29658303
TI  - Toxoplasma gondii infection induces the formation of host's nuclear granules
      containing poly(A)-binding proteins.
AB  - To study the mechanism by which human host cells respond to an infection of
      Toxoplasma gondii, we monitored the level of poly(A)-binding protein (PABP), an
      indicator of translation. Here, we report an observation of the relocalization of
      PABPs in human host cells upon T. gondii infection. Notably, the aggregates of
      PABPs formed upon infection are mainly found in the nucleus, which is a different
      response from that found after exposure to heat shock. Pyrimethamine treatment of
      the infected monolayers inhibits the multiplicity of the parasite and reverses
      the relocalization of PABP aggregates. This active interaction between the
      infected mammalian host cells and T. gondii appears to be different from that
      caused by viral infection.

PMID- 29658304
TI  - Victor W. Sidel (7 July 1931-30 January 2018).

PMID- 29658302
TI  - Molecular Epidemiology of HIV-1 Virus in Puerto Rico: Novel Cases of HIV-1
      Subtype C, D, and CRF-24BG.
AB  - HIV-1 subtype B virus is the most prevalent subtype in Puerto Rico (PR),
      accounting for about 90% of infection in the island. Recently, other subtypes and
      circulating recombinant forms (CRFs), including F(12_BF), A (01_BF), and CRF-39
      BF-like, have been identified. The purpose of this study is to assess the
      distribution of drug resistance mutations and subtypes in PR. A total of 846
      nucleotide sequences from the period comprising 2013 through 2017 were obtained
      from our "HIV Genotyping" test file. Phylogenetic and molecular epidemiology
      analyses were performed to evaluate the evolutionary dynamics and prevalence of
      drug resistance mutations. According to our results, we detected a decrease in
      the prevalence of protease inhibitor, nucleoside reverse transcriptase inhibitor
      (NRTI), and non-NRTI (NNRTI) resistance mutations over time. In addition, we also
      detected recombinant forms and, for the first time, identified subtypes C, D, and
      CRF-24BG in PR. Recent studies suggest that non-subtypes B are associated with a
      high risk of treatment failure and disease progression. The constant monitoring
      of viral evolution and drug resistance mutation dynamics is important to
      establish appropriate efforts for controlling viral expansion.

PMID- 29658305
TI  - Liver antioxidant and aerobic status improves after metformin and melatonin
      administration in a rat model of high-fat diet and mammary carcinogenesis.
AB  - Oxidative stress is involved in the development of various cancers. In the
      present study, the effect of long-term administration of peroral antidiabetic
      metformin and pineal hormone melatonin on liver antioxidant and aerobic status in
      female Sprague-Dawley rats carrying mammary tumors induced by N-methyl-N
      nitrosourea was evaluated. Both substances were administered in a preventive and
      curative manner (12 days before and 16 weeks after the carcinogen application).
      Carcinogen administration induced oxidative stress: the level of thiobarbituric
      acid reactive substances (TBARS) considered as a marker of reactive oxygen
      species (ROS) generation in liver increased as well as the level of oxidatively
      modified protein content (OMP; aldehyde and ketone derivates). Metformin
      administration restored succinate dehydrogenase and lactate dehydrogenase
      activity and associated ROS production and OMP content to the level of intact
      rats, with predominant activation of superoxide dismutase (SOD) and glutathione
      reductase (GR). Melatonin alone and in combination with metformin also decreased
      TBARS content. OMP content decreased in all groups receiving chemoprevention. The
      rise in total antioxidant capacity after melatonin and particularly metformin and
      melatonin combination might result from the initiation of anaerobic metabolism
      and increasing SOD, GR, and glutathione peroxidase activity. Long-term
      administration of metformin and melatonin exerts antioxidant properties in liver,
      especially in combination.

PMID- 29658306
TI  - 'How do they want to know?' Doctors' perspectives on making and communicating a
      diagnosis of dementia.
AB  - Recent drives to facilitate earlier identification of dementia have led to
      increased memory clinic referrals and diagnoses. This study explored the
      perspectives of memory clinic doctors on making and delivering diagnoses. Four
      focus groups were conducted with 13 psychiatrists and two geriatricians in the
      UK. Transcripts were coded line by line using NVIVO. Thematic analysis identified
      39 categories, 18 sub-themes and eight overarching themes. Inter-rater
      reliability on 31% of the data was 0.89. Increased public awareness of dementia
      was viewed positively in facilitating access to diagnosis and treatment. Doctors
      viewed diagnosis as a process and expressed concerns about limited pre-diagnostic
      counselling and post-diagnostic support. In diagnostic delivery doctors sought to
      develop a narrative drawing on the patient's report of symptoms and adjust
      explanations to patient preferences and awareness. However, tailoring the
      delivery to the individual patient was challenging when meeting for the first
      time. These consultations often involved three participants (doctor, patient and
      relative), who were felt to have differing needs and expectations. Doctors
      emphasized that delicacy was required in deciding in what could be discussed in
      front of both parties, however also stressed the importance of explicitly naming
      'dementia'. Efforts were made to balance honesty and hope when discussing
      prognosis and medication. The work was sometimes emotionally distressing, with
      limited supervision. Existing communication training was felt to be inadequate
      for consultations involving triads or people with cognitive impairment.
      Delivering a dementia diagnosis is a nuanced and challenging task. Negotiating
      honest descriptions of a life-limiting condition whilst instilling hope is
      further complicated when cognitive impairment affects comprehension.
      Misunderstandings at the time of feedback may limit patient opportunities for
      informed future planning afforded by early diagnosis. Doctors in memory clinics
      would benefit from evidence based training and supervision to prepare them for
      these emotionally challenging and complex consultations.

PMID- 29658307
TI  - Sunnybrook Protocol for Treatment of Toxic Epidermal Necrolysis.

PMID- 29658308
TI  - Granuloma Annulare-Like Granulomatous Reaction to Red Tattoo Pigment.
AB  - Cutaneous reactions to tattoos can be attributed either to trauma or to the
      exogenous pigment introduced into the skin. Red pigment is associated with a high
      sensitizing potential and is the most frequently implicated pigment inducing
      various types of histological reactions. Herein, we describe a patient with red
      tattoo pigment-induced granulomatous dermatitis that histologically revealed a
      very rare granuloma annulare-like reaction.

PMID- 29658310
TI  - The Impact of Maternal Depression on Children: A Call for Maternal Depression
      Screening.

PMID- 29658309
TI  - Individuals with HIV-1 Subtype C Infection and Cryptococcal Meningitis Exhibit
      Viral Genetic Intermixing of HIV-1 Between Plasma and Cerebrospinal Fluid and a
      High Prevalence of CXCR4-Using Variants.
AB  - The genotypic properties of human immunodeficiency virus type 1 (HIV-1) subtype C
      in individuals presenting with cryptococcal meningitis (CM) are not well
      established. Employing single-genome amplification as well as bulk PCR, cloning
      and sequencing strategies, we evaluated the genetic properties of HIV-1 subtype C
      env in 16 antiretroviral therapy-naive study participants with CM. Eleven of the
      16 participants had matched blood plasma and cerebrospinal fluid (CSF) evaluated,
      with the rest having either a plasma or CSF sample evaluated. Before
      antiretroviral therapy initiation, matched plasma and CSF-derived env sequences
      of all 11 participants displayed genetic intermixing between the two
      compartments. Overall, 7 of the 16 (~43.8%) participants harbored CXCR4-using
      variants in plasma and/or CSF, according to coreceptor usage prediction
      algorithms. This study suggests that HIV-1 subtype C genetic intermixing between
      peripheral blood and the central nervous system is common in individuals
      presenting with CM, and that CXCR4 usage is present in one or both compartments
      in approximately 44% of individuals.

PMID- 29658311
TI  - QTL mapping uncovers a semi-dwarf 1 (sdw1) allele in the barley (Hordeum vulgare)
      ND23049 line.
AB  - In barley, semi-dwarf varieties are attractive for their superior harvest index
      and lodging resistance, but many semi-dwarf barley genotypes suffer from poor
      spike emergence. We performed a genetic characterization of a semi-dwarf line
      (ND23049) that combines short stature, strong stiff culms, and adequate spike
      emergence. We developed a doubled haploid (DH) population derived by crossing
      ND23049 and the cultivar CLE253. A subset of 88 DH lines and parents were
      characterized for plant height in 2013 and 2014 and genotyped. In total, 1984
      SNPs (345 unique loci) were used to produce a linkage map of 1127.1 cM. Three
      QTLs for plant height were detected in this population and coincided with the
      HvGA20ox2/Sdw1, HvBRI1/Uzu1, and HvPRR95 gene loci. The phenotypic variation
      explained by each QTL was 75.8%, 7.7%, and 4.1%, respectively, and jointly
      explained 83.3% (2013) and 87.7% (2014) of plant height. Our results suggest that
      ND23049 contributed the "short" allele at the HvGA20ox2/sdw1 locus while CLE253
      provided "short" alleles at the HvBRI1/uzu1 and HvPRR95 loci. We identified a
      large deletion (at least 92.7 Kb), including HvGA20ox2 (Sdw1), as the causal
      mutation in ND23049. A set of tightly flanked SNP markers will help breeders to
      develop improved semi-dwarf varieties.

PMID- 29658312
TI  - Mice pancreatic islets protection from oxidative stress induced by single-walled
      carbon nanotubes through naringin.
AB  - The growing use of carbon nanotubes (CNTs) emphasizes the importance of its
      potential toxic effects on the human health. Previous studies proved that CNTs
      caused oxidative stress and decreased cell viability. On the other hand, reactive
      oxygen species (ROS) and oxidative stress impaired beta-cell functions and
      reduced the insulin secretion. However, there is not any study on the effects of
      CNTs on islets and beta-cells. Therefore, the present study aimed to evaluate the
      effects of single-walled CNTs (SWCNTs) on oxidative stress in islets in addition
      to the protective effects of naringin (NRG) as an antioxidant . We examined the
      effects of SWCNTs and naringin on islets by 3,4 3-(4,5-dimethylthiazol-2-yl)-2, 5
      diphenyltetrazolium bromide (MTT) assay; measurement of insulin secretion, ROS,
      and malondialdehyde (MDA); activities of superoxide dismutase (SOD), catalase
      (CAT), and glutathione (GSH) peroxidase (GSH-Px); and content of GSH and
      mitochondrial membrane potential (MMP). The MTT assay demonstrated that decreased
      viability of islets cells was dose-dependent with exposure to SWCNTs. Further
      studies revealed that SWCNTs decreased insulin secretion and MMP, induced the
      formation of ROS, increased the level of MDA, and decreased the activities of
      SOD, GSH-Px, and CAT and content of GSH. Furthermore, the pretreatment of islets
      with naringin significantly reverted back these changes. These findings revealed
      that SWCNTs might induce the oxidative stress to pancreatic islets, causing the
      occurrence of diabetes, and the protective effects of naringin that was mediated
      by augmentation of the antioxidant defense system of islets. Our research
      indicated the necessity for further in vivo and in vitro researches on the
      effects of SWCNTs and naringin on diabetes.

PMID- 29658313
TI  - Metabonomic analysis of toxic action of long-term low-level exposure to
      acrylamide in rat serum.
AB  - This study assessed the effects of long-term, low-dose acrylamide (AA)
      administration in rats using ultra-performance liquid chromatography-mass
      spectrometry. Forty male Wistar rats were randomly divided into the following
      four groups: control, low-dose AA (0.2 mg/kg BW), middle-dose AA (1 mg/kg BW),
      and high-dose AA (5 mg/kg BW). AA was administered to rats via drinking water ad
      libitum. After 16-week treatment, rat serum was collected for metabonomic
      analysis. Biochemical tests were further conducted to verify metabolic
      alterations. Eleven metabolites were identified with significant changes in
      intensities (increased or reduced) as a result of treatment. These metabolites
      included citric acid, pantothenic acid, isobutyryl-l-carnitine, eicosapentaenoic
      acid, docosahexaenoic acid, sphingosine 1-phosphate, LysoPC(20:4), LysoPC(22:6),
      LysoPE(20:3), undecanedioic acid, and dodecanedioic acid. Results indicate that
      chronic exposure to AA at no observed adverse effect level does not exert a toxic
      effect on rats at the body metabolism level. AA disturbed the metabolism of
      lipids and energy, affected the nervous system of rats, and induced oxidative
      stress and liver dysfunction.

PMID- 29658314
TI  - Comparing Strategies for Recruiting Small, Low-Wage Worksites for Community-Based
      Health Promotion Research.
AB  - BACKGROUND: HealthLinks is a workplace health promotion program developed in
      partnership with the American Cancer Society. It delivers a package of evidence
      based interventions and implementation support to small worksites in low-wage
      industries. As part of a randomized, controlled trial of HealthLinks, we studied
      approaches to recruiting these worksites. AIMS: This study aims to guide future
      recruitment for community-based worksite health promotion interventions by
      comparing three approaches, including leveraging relationships with community
      partners. METHOD: We recruited 78 small, low-wage worksites in King County,
      Washington, to participate in the trial via three approaches: phone calls to
      companies on a purchased list ("cold"), phone calls to a list of eligible
      companies provided by a health insurer ("lukewarm"), and personal referrals from
      local health insurers and brokers ("warm"). Eligible and interested worksites
      received an in-person visit from researchers and completed additional steps to
      enroll. RESULTS: Of the worksites screened and deemed eligible, 32% of the "cold"
      worksites enrolled in HealthLinks, as did 48% and 60%, respectively, of the
      "lukewarm" and "warm" worksites. Compared with "warm" worksites, "cold" worksites
      were twice as likely to be ineligible. DISCUSSION: Two distinct factors help
      explain why "warmer" worksites were more likely to enroll in HealthLinks. First,
      eligibility was significantly higher among warmer referrals. Second, most of the
      warm-referred worksites eligible for the study agreed to meet in person with the
      project team to hear more about the project. CONCLUSIONS: "Warmer" recruitment
      approaches yielded higher recruitment. Leveraging relationships with community
      partners can help researchers identify and successfully recruit small, low-wage
      worksites.

PMID- 29658315
TI  - The Use of Theory-Based Formative Research to Design Suicide Prevention Messaging
      for U.S. Veterans in Midlife.
AB  - BACKGROUND: Communication campaigns offer a viable mechanism to promote suicide
      prevention and reinforce mental health for U.S. veterans in midlife, a group with
      a high suicide burden. However, little empirical investigation of this type of
      messaging has been conducted, with formative campaign research conspicuously
      missing from the limited literature. AIMS: Using the theory of planned behavior
      as a guide, formative research was conducted to inform the design of suicide
      prevention messaging by (a) describing and measuring several theoretical
      constructs among our audience and (b) modeling associations between constructs
      and intentions to seek help for suicidal behaviors and mental health more
      broadly. METHODS: Telephone-based cross-sectional surveys were collected between
      2014 and 2016 from a nationally representative sample of veterans with analyses
      restricted to those aged between 44 and 65 years ( n = 809). Multiple logistic
      regression was used to identify significant factors associated with intentions to
      seek help for either suicidal behaviors or mental health. RESULTS: Perceived
      behavioral control was one of the largest predictors of intentions to seek help
      for both suicidal behaviors and mental health concerns. Descriptive norms were
      also significantly associated with suicide-related intentions. Data further
      suggest several types of attitudes (i.e., discordant beliefs, stereotypes) to
      consider when designing messages for this group. DISCUSSION: This study
      represents one of the first efforts to document and describe theoretical
      constructs and their influence on intentions among veterans in midlife to
      contribute to the development of evidence-based messaging for veterans informed
      by a conceptual framework. CONCLUSION: Findings have important implications as
      the use of communication strategies for suicide prevention grows increasingly
      popular.

PMID- 29658316
TI  - NMR-based metabolomics to evaluate the milk composition from Friesian and
      autochthonous cows of Northern Italy at different lactation times.
AB  - It is well established that different factors affect milk composition in cows and
      that milk composition, in turn, affect both technological and nutritional
      qualities. In this respect the comprehension of the metabolic variability of milk
      composition in relation to the lactation time as well as to the genetic
      background may be of paramount importance for the agri-food industries. In the
      present study we investigated the variations of the metabolic profiles during
      lactation in milks obtained from Friesian and autochthonous races from Northern
      Italy by 1H NMR metabolomics. Furthermore, the external factors influencing the
      milk composition were minimized: the cows were breeded in the same farm, were fed
      with the same diet and were paired for the lactation interval and lactation
      stage. Our results showed a difference in milk composition between races and in
      relation to late lactation. The PLS-DA analysis permitted to distinguish the
      Friesian and autochthonous cow milks at the investigated different lactation
      times. Interestingly, the metabolites significantly involved into the
      discrimination between races appeared to be also technological property
      parameters, highlighting the importance of maintaining the biodiversity of cow
      breeds. Therefore, NMR-based metabolomics of milk could represent an informative
      tool to identify metabolites involved in milk quality both from a nutritional and
      industrial perspective.

PMID- 29658317
TI  - Transcriptome characterization and screening of molecular markers in ecologically
      important Himalayan species (Rhododendron arboreum).
AB  - Rhododendron arboreum is an ecologically prominent species, which also lends
      commercial and medicinal benefits in the form of palatable juices and useful
      herbal drugs. Local abundance and survival of the species under a highly
      fluctuating climate make it an ideal model for genetic structure and functional
      analysis. However, a lack of genomic data has hampered additional research. In
      the present study, cDNA libraries from floral and foliar tissues of the species
      were sequenced to provide a foundation for understanding the functional aspects
      of the genome and to construct an enriched repository that will promote genomics
      studies in the genera. Illumina's platform facilitated the generation of ~100
      million high-quality paired-end reads. De novo assembly, clustering, and
      filtering out of shorter transcripts predicted 113 167 non-redundant transcripts
      with an average length of 1164.6 bases. Of these, 71 961 transcripts were
      categorized based on functional annotations in the Gene Ontology database,
      whereby 5710 were grouped into 141 pathways and 23 746 encoded for different
      transcription factors. Transcriptome screening further identified 35 419
      microsatellite regions, of which, 43 polymorphic loci were characterized on 30
      genotypes. Seven hundred and nineteen transcripts had 811 high-quality single
      nucleotide polymorphic variants with a minimum coverage of 10, a total score of
      20, and SNP% of 50.

PMID- 29658318
TI  - What makes children with cerebral palsy vulnerable to malnutrition? Findings from
      the Bangladesh cerebral palsy register (BCPR).
AB  - PURPOSE: To assess the nutritional status and underlying risk factors for
      malnutrition among children with cerebral palsy in rural Bangladesh. MATERIALS
      AND METHODS: We used data from the Bangladesh Cerebral Palsy Register; a
      prospective population based surveillance of children with cerebral palsy aged 0
      18 years in a rural subdistrict of Bangladesh (i.e., Shahjadpur). Socio
      demographic, clinical and anthropometric measurements were collected using
      Bangladesh Cerebral Palsy Register record form. Z scores were calculated using
      World Health Organization Anthro and World Health Organization AnthroPlus
      software. RESULTS: A total of 726 children with cerebral palsy were registered
      into the Bangladesh Cerebral Palsy Register (mean age 7.6 years, standard
      deviation 4.5, 38.1% female) between January 2015 and December 2016. More than
      two-third of children were underweight (70.0%) and stunted (73.1%). Mean z score
      for weight for age, height for age and weight for height were -2.8 (standard
      deviation 1.8), -3.1 (standard deviation 2.2) and -1.2 (standard deviation 2.3)
      respectively. Moderate to severe undernutrition (i.e., both underweight and
      stunting) were significantly associated with age, monthly family income, gross
      motor functional classification system and neurological type of cerebral palsy.
      CONCLUSIONS: The burden of undernutrition is high among children with cerebral
      palsy in rural Bangladesh which is augmented by both poverty and clinical
      severity. Enhancing clinical nutritional services for children with cerebral
      palsy should be a public health priority in Bangladesh. Implications for
      Rehabilitation Population-based surveillance data on nutritional status of
      children with cerebral palsy in Bangladesh indicates substantially high burden of
      malnutrition among children with CP in rural Bangladesh. Children with severe
      form of cerebral palsy, for example, higher Gross Motor Function Classification
      System (GMFCS) level, tri/quadriplegic cerebral palsy presents the highest
      proportion of severe malnutrition; hence, these vulnerable groups should be
      focused in designing nutrition intervention and rehabilitation programs.
      Disability inclusive and focused nutrition intervention programme need to be kept
      as priority in national nutrition policies and nutrition action plans specially
      in low- and middle-income countries. Community-based management of malnutrition
      has the potential to overcome this poor nutritional scenario of children with
      disability (i.e., cerebral palsy). The global leaders such as World Health
      Organization, national and international organizations should take this in
      account and conduct further research to develop nutritional guidelines for this
      vulnerable group of population.

PMID- 29658320
TI  - Screening of medicinal plants traditionally used in Peruvian Amazon for in vitro
      antioxidant and anticancer potential.
AB  - Plants mentioned in this study have numerous records in traditional Peruvian
      medicine being used in treatment of cancer and other diseases likely to be
      associated with oxidative stress. Amongst the eight plant species tested, only
      Dysphania ambrosioides exhibited combinatory antioxidant and anti-proliferative
      effect on a broad spectrum of cancer cells (DPPH and ORAC values = 80.6 and 687.3
      MUg TE/mg extract, respectively; IC50 against Caco-2, HT-29 and Hep-G2 = 129.2,
      69.9 and 130.6, respectively). Alkaloids and phenolic compounds might
      significantly contribute to anticancer/antioxidant activity of this plant. The
      results justify the traditional medicinal use of this plant. Our findings further
      suggest that D. ambrosioides might serve as a prospective material for further
      development of novel plant-based antioxidant and/or anti-proliferative agents.
      Detailed analysis of chemical composition together with toxicology assessments
      and in vivo antioxidant/anti-proliferative activity of this plant should be
      carried out in order to verify its potential practical use.

PMID- 29658319
TI  - Preparation of poly-l-lysine-based nanoparticles with pH-sensitive release of
      curcumin for targeted imaging and therapy of liver cancer in vitro and in vivo.
AB  - Poly-l-lysine (PLL) nanoparticle (NP) system was prepared for the controlled
      release of curcumin (CUR) by pH stimuli, and its theranostic efficacy on cancer
      was compared to that of CUR solution in vitro and in vivo. Deoxycholic acid
      (DOCA), methoxy polyethylene glycol (MPEG) and cyanine 5.5 (cy5.5) were
      conjugated to the amine group of PLL through condensation reaction (PLL-DOCA-MPEG
      cy5.5), followed by encapsulation of CUR by dialysis method (PLL-DOCA-MPEG
      cy5.5/CUR NPs). The composition, morphology and size distribution of PLL-DOCA
      MPEG-cy5.5 NPs were characterized by proton nuclear magnetic resonance (1H NMR),
      transmission electron microscopy (TEM) and dynamic light scattering (DLS),
      respectively. In vitro tests exhibited that changes in the charge and size of the
      NPs at low pH led to the improved cellular uptake of CUR into human hepatoma
      Hep3B cell line by electrostatically absorptive endocytosis. PEGylation with MPEG
      was turn out to be very effective to have a prolonged blood circulation time, in
      turn increased the EPR effect. In addition, the incorporation of Cy5.5 into NPs
      provided successful biodistribution images in vivo and ex vivo. Our findings
      suggest that PLL-DOCA-MPEG-cy5.5/CUR NPs may have promising applications in
      cancer theranosis.

PMID- 29658321
TI  - The neurobiology of focus and distraction: The case for incorporating mindfulness
      into leadership.
AB  - Increasingly health leaders are experiencing greater demands and pressures, which
      require the need for better focus while limiting unwarranted distractions. This
      article offers a neurobiological explanation of how the brain focuses and becomes
      distracted, in order to help health leaders gain insight into their own
      effectiveness. Two main neural circuits are contrasted: the mind-wandering
      default mode circuit and the attentional central executive system. These two
      systems act in an antagonistic pairing, where the degree of toggling between
      systems is associated with the degree a person can sustain focus and filter out
      unwarranted distractions. Excessive multitasking appears to compromise the neural
      switch of these two systems, thereby diminishing our focus and concentration. In
      contrast, mindfulness practice is shown to have the opposite effect by enhancing
      the neural switch, thereby enhancing leadership focus that can lead to greater
      flexibility, foresight, regulation, and creativity. To conclude, leaders who are
      excessively distracted, such as with multitasking, may be compromising cognitive
      brain functioning, while engaging in mindfulness may replenish the brain and
      thereby enhance leaders' ability to sustain focus and tap into higher cognitive
      functioning.

PMID- 29658322
TI  - Clinical effectiveness and versatility of a sealing hemostatic patch (HEMOPATCH)
      in multiple surgical specialties.
AB  - INTRODUCTION: Intraoperative surgical sealants and hemostatic agents have been
      shown to reduce postoperative complications, transfusions, and hospital resource
      utilization. Despite availability of these agents, the incidence and burden of
      bleeding remains high and surgeons' requirements for hemostatic control continue
      to evolve. A burgeoning class of hemostatic agents are hemostatic patches, which
      offer package-to-patient readiness and direct application. In addition,
      hemostatic patches may provide tissue sealing capabilities. Areas covered: This
      review focuses on the clinical effectiveness, versatility, and surgical
      efficiency of HEMOPATCH as a surgical sealant and hemostatic agent in various
      surgical specialties including: cardiac, digestive (hepatic, gastrointestinal,
      pancreatic), urological, neurological, and endocrine. Expert commentary: Among
      hemostatic patches, HEMOPATCH is a valuable tool to stop bleeding without adverse
      events across various surgical specialties. Clinical evidence demonstrates the
      safety, clinical effectiveness, and versatility of HEMOPATCH as a unique surgical
      adjunct in patients undergoing complex and routine surgical procedures. Larger
      randomized-controlled clinical studies, or clinical registries, will continue to
      be used to evaluate its performance and versatility, particularly for sealing
      tissues and closing the dura. In the current field of surgical sealing and
      hemostasis, however, HEMOPATCH represents the next step in improving patient
      outcomes.

PMID- 29658323
TI  - Two new anthraquinone derivatives and one new triarylbenzophenone analog from
      Selaginella tamariscina.
AB  - Two new anthraquinone derivatives, selaginones A (1) and B (2), and one new
      triarylbenzophenone analog, selagibenzophenone B (3), were isolated from
      Selaginella tamariscina (Beauv.) Spring. Their structures were established by 1D
      , 2D-NMR and HR-ESI-MS data. Compounds 1 and 2 represent the uncommon examples of
      aryl substituted anthraquinone derivatives. Especially, compound 2 is a unique
      anthranone with exceptional structural feature, in which a p-hydroxyphenyl moiety
      is attached to the C-10 position. Compound 3 is the second naturally occurring
      triarylbenzophenone and showed moderate activity against SMCC-7721 and MHCC97-H
      cell lines with IC50 values of 39.8, 51.5 MUM respectively.

PMID- 29658324
TI  - Prediagnostic body size and risk of amyotrophic lateral sclerosis death in 10
      studies.
AB  - OBJECTIVES AND METHODS: Using pooled multivariable-adjusted rate ratios (RR), we
      explored relationships between prediagnostic body-mass-index (BMI), waist-to-hip
      ratio (WHR), and weight-gain during adulthood, and ALS in 419,894 women and
      148,166 men from 10 community-based cohorts in USA, Europe, and Australia; 428
      ALS deaths were documented in women and 204 in men. RESULTS: Higher mid-to-later
      adulthood BMI was associated with lower ALS mortality. For 5 kg/m2 increased BMI,
      the rate was 15% lower (95% confidence interval [CI]: 4-24%; p = 0.005). Although
      a clear linear trend was not evident for WHR at enrollment (p = 0.099)
      individuals in the highest cohort-specific quartile had 27% (95% CI: 0-47%; p =
      0.053) lower ALS compared to those in the lowest. BMI in early adulthood did not
      predict ALS; fewer than 10% of participants had early adulthood BMI >25 kg/m2,
      limiting power. Weight-gain during adulthood was strongly associated with lower
      ALS; for an additional 1kg gain in weight/year, the RR = 0.43 (95% CI: 0.28-0.65;
      p < 0.001). Associations persisted when adjusted for diabetes at enrollment,
      restricted to never-smokers, and ALS deaths in the 5 years after enrollment were
      excluded (accounting for recent weight loss). CONCLUSIONS: These findings confirm
      somewhat conflicting, underpowered evidence that adiposity is inversely
      associated with ALS. We newly demonstrate that weight-gain during adulthood is
      strongly predictive of lower ALS risk.

PMID- 29658326
TI  - Cardioprotective Role of Colchicine Against Inflammatory Injury in a Rat Model of
      Acute Myocardial Infarction.
AB  - BACKGROUND: Inflammation plays a crucial role in the pathophysiology of
      myocardial ischemia/reperfusion (I/R) injury. A clinical trial has recently
      reported a smaller infarct size in a cohort of patients with ST-segment elevation
      myocardial infarction (MI) treated with a short colchicine course. The mechanism
      underlying colchicine-induced cardioprotection in the early MI phase remains
      unclear. We hypothesized that a short pretreatment with colchicine could induce
      acute beneficial effects by protecting the heart against inflammation in
      myocardial I/R injury. METHODS AND RESULTS: Rats were subjected to 40-minute left
      anterior descending coronary occlusion, followed by 120-minute reperfusion.
      Colchicine (0.3 mg/kg) or a vehicle was administered per os 24 hours and
      immediately before surgery. Infarct size was significantly reduced in the
      colchicine group (35.6% +/- 3.0% vs 46.6% +/- 3.3%, P < .05). The beneficial
      effects of colchicine were associated with an increased systemic interleukin-10
      (IL-10) level and decreased cardiac transforming growth factor-beta level.
      Interleukin-1beta was found to increase in a "time of reperfusion"-dependent
      manner. Colchicine inhibited messenger RNA expression of caspase-1 and pro-IL-18.
      Interleukin-1beta injected 10 minutes prior to myocardial ischemia induced
      greater infarct size (58.0% +/- 2.0%, P < .05) as compared to the vehicle.
      Colchicine combined to IL-1beta injection significantly decreased infarct size
      (47.1% +/- 2.2%, P < .05) as compared to IL-1beta alone, while colchicine alone
      exhibited a significantly more marked cardioprotective effect than the colchicine
      IL-1beta association. CONCLUSION: The cardioprotection induced by a short
      colchicine pretreatment was associated with an anti-inflammatory effect in the
      early reperfusion phase in our rat MI model.

PMID- 29658325
TI  - Fabrication of a drug delivery system that enhances antifungal drug corneal
      penetration.
AB  - Fungal keratitis (FK) remains a severe eye disease, and effective therapies are
      limited by drug shortages and critical ocular barriers. Despite the high
      antifungal potency and broad spectrum of econazole, its strong irritant and
      insolubility in water hinder its ocular application. We designed and fabricated a
      new drug delivery system based on a polymeric vector for the ocular antifungal
      application of econazole. This novel system integrates the advantages of its
      constituent units and exhibits superior comprehensive performance. Using the new
      system, drug content was significantly increased more than 600 folds. The results
      of in vivo and in vitro experiments demonstrated that the econazole-loaded
      formulation exhibited significantly enhanced corneal penetration after a single
      topical ocular administration, excellent antifungal activity, and good tolerance
      in rabbits. Drug concentrations and ocular relative bioavailability in the cornea
      were 59- and 29-time greater than those in the control group, respectively.
      Following the topical administration of one eye drop (50 MUL of 0.3% w/v
      econazole) in fungus-infected rabbits, a high concentration of antimycotic drugs
      in the cornea and aqueous humor was sustained and effective for 4 h. The
      mechanism of corneal penetration was also explored using dual fluorescent
      labeling. This novel drug delivery system is a promising therapeutic approach for
      oculomycosis and could serve as a candidate strategy for use with various
      hydrophobic drugs to overcome barriers in the treatment of many other ocular
      diseases.

PMID- 29658327
TI  - Adherence to Oral Anticoagulants in Atrial Fibrillation: An Australian Survey.
AB  - BACKGROUND: The aim of this study was to investigate the proportion of patients
      who have suboptimal adherence to oral anticoagulant (OAC), identify the
      predictors of adherence, and determine whether patient-related factors vary
      across adherence levels in Australia. METHODS: Respondents were recruited for an
      online survey using Facebook. Survey instruments included the Morisky Medication
      Adherence Scale, the Anticoagulation Knowledge Tool, the Perception of
      Anticoagulant Treatment Questionnaires, and a modified Cancer Information
      Overload scale. Predictors of medication adherence were identified using ordinal
      regression analysis. RESULTS: Of the 386 responses eligible for analysis, only
      54.9% reported a high level of adherence. Participants aged 65 years or younger
      were less likely to have high adherence compared to older participants (odds
      ratio [OR], 0.54; 95% confidence interval [CI], 0.33-0.88; P = .013), while
      females were more likely to be highly adherent compared to males (OR, 1.69; 95%
      CI, 1.08-2.64; P = .023). The analyses showed that age, gender, treatment
      satisfaction, information overload, concerns about making mistake when taking
      OACs, and cost of medication were significant predictors of adherence.
      CONCLUSION: Self-reported suboptimal adherence to OAC is common among patients
      with atrial fibrillation. A focus on supporting people who are at higher risk of
      suboptimal adherence is needed to maximize the benefit of OAC therapy in this
      population.

PMID- 29658328
TI  - Effects of Enoxaparin on Intravascular Sclerostin Release in Healthy Men.
AB  - Sclerostin (Scl) is implicated in vascular calcification and angiogenesis and
      localizes within vasculature. Its molecule incorporates a heparin-binding site
      that implies also binding to endothelial glycocalyx. We preliminary tested
      whether intravenous (IV) low-molecular-weight heparin enoxaparin can stimulate
      intravascular release of this calcification inhibitor in humans. Sixteen male
      volunteers were injected with a bolus of 1 mg/kg body weight of enoxaparin. After
      10 minutes, plasma immunoreactive Scl levels increased uniformly by a mean of
      184% versus baseline level of 0.56 +/- 0.17 ng/mL ( P = .0004). Plasma Scl levels
      were found still elevated after 2 and 6 hours (with a median of 20.9% and 8.69%,
      respectively) and became normal after 24 hours. The percentage of increase
      (Delta) in plasma Scl after 10 minutes was directly correlated with enoxaparin
      dose per kg/m2 of body mass index (rho = 0.587, P = .017) and strongly inversely
      correlated with the preinjection Scl levels (rho = -0.747, P = .0008). A robust
      negative association between the DeltaScl increase after 10 minutes and the
      DeltaScl decrease after 2 hours versus 10 minutes was observed (rho = -0.835, P <
      .0001). Complementary in vitro spiking experiment showed no effects of enoxaparin
      addition and whole blood incubation on plasma Scl levels when measured with the
      immunoassay. This study shows that enoxaparin has a stimulating effect on the
      intravascular release of calcification inhibitor Scl in healthy men. This novel
      pharmacological action of the popular anticoagulant drug seems important in
      cardiovascular medicine.

PMID- 29658329
TI  - Identification of a novel mutation in FGFR1 gene in patients with Kallmann
      syndrome by high throughput sequencing.
AB  - : Kallmann syndrome (KS) is a rare clinical and genetic heterogeneity disease,
      which is familial or sporadic. KS is known to have three patterns of inheritance:
      X linked recessive inheritance, autosomal dominant inheritance and rare autosomal
      recessive inheritance. Here, we report a sibling pedigree with autosomal dominant
      inheritance of KS, and we identified a novel heterozygous frameshift mutation
      c.299_300insCCGCAGACTCCGGCCTCTATGC (p.C101Rfs*17) in FGFR1 gene using whole-exome
      sequencing (WES). The mutation and affection status were cosegregated. The
      mutation is not present in the dbSNP, 1000 Genome, ExAC, and gnomAD databases.
      The discovery of this new mutation in the FGFR1 gene enriches the spectrum of
      FGFR1 mutations in patients with KS. ABBREVIATIONS: FGFR1: fibroblast growth
      factor receptor 1; HH: hypogonadotropic hypogonadism; KS: Kallmann syndrome; MRI:
      magnetic resonance imaging; WES: whole-exome sequencing.

PMID- 29658330
TI  - Comparative cytotoxicity and apoptotic pathways induced by nanosilver in human
      liver HepG2 and L02 cells.
AB  - Silver nanoparticles are used in many commercial products in daily life. Exposure
      to nanosilver has hepatotoxic effects in animals. This study investigated the
      cytotoxicity associated with polyvinylpyrrolidone-coated nanosilver (23.44 +/-
      4.92 nm in diameter) exposure in the human hepatoma cell line (HepG2) and normal
      hepatic cell line (L02), and the molecular mechanisms induced by nanosilver in
      HepG2 cells. Nanosilver, in doses of 20-160 MUg mL-1 for 24 and 48 h, reduced
      cell viability in a dose- and time-dependent manner and induced cell membrane
      leakage and mitochondria injury in both cell lines; these effects were more
      pronounced in HepG2 cells than in L02 cells. Intracellular oxidative stress was
      documented by reactive oxygen species (ROS) being generated in HepG2 cells but
      not in L02 cells, an effect possibly due to differential uptake of nanosilver by
      cancer cells and normal cells. In HepG2 cells, apoptosis was documented by
      finding that ROS triggered a decrease in mitochondrial membrane potential, an
      increase in cytochrome c release, activation of caspase 3 and caspase 9, and a
      decrease in the ratio of Bcl-2/Bax. Furthermore, nanosilver activated the Fas
      death receptor pathway by downregulation of nuclear factor-kappaB and activation
      of caspase 8 and caspase 3. These results suggest that apoptosis induced by
      nanosilver in HepG2 cells is mediated via a mitochondria-dependent pathway and
      the Fas death receptor pathway. These findings provide toxicological and
      mechanistic information that can help in assessing the effects of nanosilver in
      biological systems, including the potential for anticancer activities.

PMID- 29658331
TI  - Patients' exposure to PVC plasticizers from ECMO circuits.
AB  - BACKGROUND: ECMO is a therapeutic act with a high risk of exposure to
      diethylhexylphthalate (DEHP), plasticizer from PVC tubings. The replacement of
      this plasticizer with alternative compounds is recommended but the risks
      associated with the use of new plasticizers have not been evaluated in ECMO
      situations. METHODS: Ex vivo ECMO models were performed with different flow rates
      over 6 days to evaluate the migration of plasticizers and their potential toxic
      risk for patient. The release of plasticizers during ECMO was measured and
      compared to reference value (derived no effect level, DNEL) and to cytotoxic
      concentration carried out with MTT test. RESULTS: Trioctyltrimellitate (TOTM),
      main plasticizer present in circuit (44% w/w), is weakly released during ECMO.
      Concentrations are not cytotoxic and exposure doses are lower than DNEL. In
      contrast, DEHP doses are higher than the DNEL despite a lower presence of DEHP in
      the circuit (0.2%). We have shown that DEHP is not coming from the circuit but
      from the priming bag. Replacing this bag with a multilayer one avoids the
      exposure to DEHP. CONCLUSION: Our study shows that circuits made of PVC
      plasticized with TOTM against DEHP improves the safety of ECMO.

PMID- 29658332
TI  - Structurally diverse diterpenoids from Trigonostemon howii.
AB  - Phytochemical investigation on the stems and leaves of Trigonostemon howii
      resulted in the isolation of a new abietane diterpenoid, trigohowimine A (1),
      along with seven known structurally diverse diterpenoids (2-8). The structure of
      1 was elucidated by extensive spectroscopic methods and the known compounds were
      identified by comparison with data reported in the literature. New compound 1 was
      evaluated for its cytotoxicities against five human cancer cell lines: HL-60,
      SMMC-7721, A-549, MCF-7 and SW480. Compound 1 showed significant inhibitory
      effects against various human cancer cell lines with IC50 values ranging from
      0.82 to 8.53 MUM.

PMID- 29658334
TI  - The modified Brunelli procedure: a simple passage for the flexor carpi radialis
      tendon graft.

PMID- 29658333
TI  - Mucinous breast carcinoma with tall columnar cells.
AB  - Mucinous carcinoma of the breast represents 1%-4% of all breast cancers. The
      World Health Organization classification divides this type of tumour into three
      different subtypes: mucinous carcinoma, mucinous carcinoma with tall columnar
      cells (mucinous cystadenocarcinoma and columnar cell mucinous carcinoma) and
      signet ring cell carcinoma. A 74-year-old woman presented a tumour with
      inflammatory features in the upper outer quadrant of her left breast, 7 cm in
      diameter. The core biopsy showed infiltrating ductal carcinoma of no specific
      type. The tumour-node-metastasis clinical staging was T4cN3M0 (Stage IIIC). She
      received neoadjuvant chemotherapy, underwent left mastectomy with radical
      axillary resection and subsequently received radiotherapy and chemotherapy. The
      histological examination of the surgical specimen revealed two solid tumors in
      the tail of Spence, which corresponded to adenocarcinoma with high columnar
      cells. The patient died 16 months after the diagnosis, suffering from pulmonary
      metastases and anterior chest wall infiltration. A review of the literature
      revealed only 21 reports of mucinous carcinoma of the breast with tall columnar
      cells, including our case. This is only the third time that the specific
      histological type of columnar cell mucinous carcinoma has been reported in the
      literature.

PMID- 29658335
TI  - A case report of caecal herniation through the foramen of Winslow.
AB  - Caecal herniation through the foramen of Winslow is a rare entity of which
      radiologist should be aware. We present a case of this entity in a patient
      presenting with diabetic ketoacidosis and ongoing epigastric pain. Abdominal
      computed tomography demonstrated herniation of the caecum into the lesser sac via
      the foramen of Winslow. Despite the caecum appearing viable at the time of
      surgery, the surgeons performed a right hemicolectomy via laparotomy to prevent
      future recurrence.

PMID- 29658336
TI  - Nodular fasciitis involving the palm.
AB  - Nodular fasciitis (NF) is a self-limiting fibrous neoplasm that can be mistaken
      for a soft tissue sarcoma. It is characterised by rapid growth, slight pain and
      local tenderness. Although it is frequently found in the forearm, a lesion distal
      to the wrist is quite rare. We present two unusual cases of NF involving the
      palm, supported by detecting ubiquitin specific protease 6 gene rearrangement.
      The first patient had non-intraneural NF presenting as peripheral neuropathy
      affecting the digital nerve while the second patient suffered from painless, non
      tender NF in the palm, which had not regressed spontaneously during the five
      months prior to surgery.

PMID- 29658337
TI  - Surveillance imaging for sporadic renal angiomyolipoma less than 40 mm: lessons
      learnt and recommendations from the experience of a large district general
      hospital.
AB  - Introduction Sporadic renal angiomyolipomas, although benign in natural can cause
      life-threatening spontaneous haemorrhage. Surveillance of smaller lesions is
      recommended but there is no guidance on the surveillance interval or modality.
      Our aim was to study our sporadic angiomyolipoma population to determine the
      growth rate, factors that were associated with a higher growth rate and design a
      surveillance programme. Materials and methods All sporadic renal angiomyolipomas
      diagnosed between September 2009 and March 2015 were included. Patients with a
      diagnosis of tuberous sclerosis were excluded. Results A total of 217 sporadic
      renal angiomyolipomas were diagnosed. The median follow-up was 24 months (range
      10-118 months). The median size at diagnosis was 9.00 mm with a mean growth rate
      of 0.13 mm/year (standard deviation 0.88). One hundred and fifty angiomyolipomas
      (69%) were shown to have negative or zero growth. In the remaining 67, 59 had a
      growth rate of less than 2.00 mm/year. Size of angiomyolipoma, tumour burden and
      age were not associated with a higher growth rate on multivariate analysis.
      Conclusion The majority of sporadic angiomyolipomas are small and do not grow.
      Our practice is to perform surveillance for those greater than 20 mm, with five
      yearly ultrasound scans for 21-29 mm, and two-yearly surveillance for 30-39 mm
      tumours.

PMID- 29658338
TI  - Chyle leak following an axillary sentinel lymph node biopsy for breast cancer in
      a patient with superior vena caval thrombosis - a case report and review of the
      literature.
AB  - Chyle leak is a very rare complication following an axillary lymph node
      dissection. We report a case of chyle leak following sentinel lymph node biopsy
      in a patient with breast cancer with superior vena caval thrombosis. To our
      knowledge, this is the first case report of chyle leakage following axillary
      sentinel lymph node biopsy. We describe the aetiology, prevention and treatment
      strategy that can be adopted in these patients.

PMID- 29658340
TI  - A novel use of cement as a salvage procedure in patients with complex spinal
      injuries with proximal junctional failure.
AB  - Long-construct fixations can be complicated by proximal junctional kyphosis. In
      elderly, high-risk patients with numerous comorbidities, lengthy surgical times
      and increased blood loss associated with revision osteotomies and extension of
      fusions are not often tolerated and pose serious life-threatening risks. We
      present a salvage technique used in a patient with proximal junctional failure
      and demonstrate its role in improving symptoms and functionality in those not
      deemed fit for major surgery. Pre- and postoperative pain scores in accordance
      with the visual analogue scale, walking distances and radiographs were reviewed
      in a patient who underwent the salvage technique to ascertain the subjective and
      objective difference in pain and functionality. The patient showed marked
      improvement in pain scores and walking distances postoperatively. Additionally,
      the degree of proximal junctional kyphosis was lower on postoperative
      radiographs. While holding risks of its own, our described technique can be
      performed in select cases and is a good salvage procedure in high-risk patients.
      It prevents their exposure to the risks that accompany large revision operations
      and fusion models with further potential to fail. We recommend that our technique
      is performed only at specialist centres.

PMID- 29658339
TI  - Refractory hypercalcaemia secondary to localised gastrointestinal stromal tumour.
AB  - Gastrointestinal stromal tumours are a rare form of intra-abdominal neoplasm
      derived from mesenchymal tissue, typically presenting with abdominal pain,
      anaemia or bleeding into the bowel or abdominal cavity. Hypercalcaemia is an
      unusual complication, having been documented in only seven previous patients, all
      of whom had advanced metastatic disease. We present a case of treatment-resistant
      hypercalcaemia in a patient with non-metastatic gastrointestinal stromal tumour,
      which resolved following excision of the tumour.

PMID- 29658341
TI  - Calcific myonecrosis: diagnostic dilemma.
AB  - Calcific myonecrosis is a rare benign condition affecting mainly the muscles of a
      single leg compartment. It is thought to follow a history of trauma with a latent
      period of years. Patients present with a slowly growing mass. Differential
      diagnosis from a malignant tumour can be made from the history and the
      distinctive radiographical features of a fusiform lesion with predominantly
      peripheral calcifications. Magnetic resonance imaging may be necessary to confirm
      the diagnosis; treatment is largely symptomatic.

PMID- 29658342
TI  - A rare case of haemorrhagic shock secondary to spontaneous rupture of a branch of
      the left colic artery and the right gastric artery.
AB  - Spontaneous splanchnic artery rupture is associated with up to 70% mortality.
      Affected vessels are often aneurysmal, secondary to atherosclerosis. We report,
      to our knowledge, the only case of spontaneous rupture of a branch of the left
      colic artery and the right gastric artery, possibly secondary to vasculitis.

PMID- 29658344
TI  - Effect of 12-month treatment with metformin and/or oral contraceptives on health
      related quality of life in polycystic ovary syndrome.
AB  - Health-related quality of life (HRQoL) is impaired in polycystic ovary syndrome
      (PCOS), but the effect of treatment with metformin (M) and/or oral contraceptives
      (OCP) is undetermined. To assess changes in HRQoL during 12-month randomized
      treatment with M, OCP or M + OCP in PCOS. Ninety women with PCOS were randomized
      to treatment with M, OCP or M + OCP. HRQoL was evaluated by a PCOS-specific
      visual analog scale (PCOS-VAS) regarding 1: Facial hair, 2: Body hair, 3: Acne,
      4: Irregular menses, 5: Weight and 6: PCOS in general, and Short Form 36 (SF-36).
      PCOS-VAS1(facial hair) improved during treatment with OCP (n = 23) compared to M
      (n = 19), and during M + OCP (n = 23) compared to M treatment, whereas changes in
      PCOS-VAS2-6 and SF-36 scores were comparable between the three medical
      intervention groups. Pooled data (n = 65) showed improved PCOS-VAS scores during
      treatment (all p < .05), but changes in PCOS-VAS were unassociated with changes
      in BMI or FG-scores despite significant weight-loss during treatment with M (-3.0
      kg (-10.3; 0.6)) and M + OCP (-1.9 kg (-4.9; 0.1)) and decreased FG-score during
      M + OCP treatment (median (quartiles)). PCOS-VAS scores improved significantly
      and to the same extent during treatment with M, OCP or M + OCP.

PMID- 29658343
TI  - Older age, higher perceived disability and depressive symptoms predict the amount
      and severity of work-related difficulties in persons with multiple sclerosis.
AB  - PURPOSE: This cross-sectional study aims to identify the predictors of work
      related difficulties in a sample of employed persons with multiple sclerosis as
      addressed with the Multiple Sclerosis Questionnaire for Job Difficulties.
      MATERIALS AND METHODS: Hierarchical linear regression analysis was conducted to
      identify predictors of work difficulties: predictors included demographic
      variables (age, formal education), disease duration and severity, perceived
      disability and psychological variables (cognitive dysfunction, depression and
      anxiety). The targets were the questionnaire's overall score and its six
      subscales. RESULTS: A total of 177 participants (108 females, aged 21-63) were
      recruited. Age, perceived disability and depression were direct and significant
      predictors of the questionnaire total score, and the final model explained 43.7%
      of its variation. The models built on the questionnaire's subscales show that
      perceived disability and depression were direct and significant predictors of
      most of its subscales. CONCLUSIONS: Our results show that, among patients with
      multiple sclerosis, those who were older, with higher perceived disability and
      higher depression symptoms have more and more severe work-related difficulties.
      The Multiple Sclerosis Questionnaire for Job Difficulties can be fruitfully
      exploited to plan tailored actions to limit the likelihood of near-future job
      loss in persons of working age with multiple sclerosis. Implications for
      rehabilitation Difficulties with work are common among people with multiple
      sclerosis and are usually addressed in terms of unemployment or job loss. The
      Multiple Sclerosis Questionnaire for Job Difficulties is a disease-specific
      questionnaire developed to address the amount and severity of work-related
      difficulties. We found that work-related difficulties were associated to older
      age, higher perceived disability and depressive symptoms. Mental health issues
      and perceived disability should be consistently included in future research
      targeting work-related difficulties.

PMID- 29658345
TI  - Osmolyte taurine induction in UVA exposed human retinal pigment epithelial cells.
AB  - AIM: To explore the osmolytes expression in ultraviolet (UVA) stressed human
      retinal pigment epithelial cells. METHODS: Osmolyte transporters and vascular
      endothelial growth factor (VEGF) messenger RNA (mRNA) were determined by real
      time polymerase chain reaction (PCR). Osmolyte uptake was measured by
      radioimmunoassay. VEGF concentrations were determined by immunoassay and enzyme
      linked immunosorbent assay (ELISA). Osmolyte taurine transporter (TAUT) were
      silenced by siRNA technology. RESULTS: Hypertonicity accelerated osmolyte betaine
      uptake, myoinositol uptake, and taurine uptake, compared to normotonic stress.
      UVA irradiation also accelerated osmolyte transporters expression and osmolytes
      uptake. Especially, osmolyte taurine remarkably inhibited VEGF release induced by
      UVA irradiation. VEGF in the UVA stressed retinal pigment epithelial cell
      supernatant was accumulated slow after taurine preincubation. VEGF expression
      increased significantly in UVA-stressed cells after TAUT silencing. Moreover,
      taurine reduced the VEGF level in human ocular aqueous humor. CONCLUSION: The
      inhibition of VEGF by osmolyte taurine plays the crucial role in retina adaption
      to UVA irradiation.

PMID- 29658346
TI  - Association between thrombophilia gene polymorphisms and recurrent pregnancy loss
      risk in the Iranian population.
AB  - : Miscarriage is the most common complication in pregnancy. Considering the
      importance of the problem thrombophilia in pregnant women and its association
      with recurrent pregnancy loss (RPL), analysis of polymorphisms of genes involved
      in thrombophilia can be useful. We investigated the frequency and association
      between ten polymorphisms of seven thrombophilia genes and RPL in an Iranian
      population. This case-control study was conducted on 200 women with recurrent
      pregnancy loss and also on 200 women with at least one successful pregnancy as
      the control group. Using PCR-RFLP, DNA from samples were analyzed for carrying
      A5279G, A4070G, and FV Leiden of factor V; FXIII (Val34Leu); FII (A20210G); BF (
      455 G/A); ITGB3 (1565T/C); 677C/T and 1298A/C of MTHFR; and PAI-1 (-675 I/D,
      5G/4G) polymorphisms. The BF(-455 G/A), MTHFR (677 C/T, 1298A/ C), PAI-1 (-675
      I/D,4G/ 5G), FV Leiden, FV (A5279G), FXIII (Val34Leu) polymorphisms, which had
      shown positive relation, and ITGB3 1565T/C were the polymorphisms with negative
      relation to RPL. But in this study it is indicated that there is no significant
      association between FII (A20210G) and FV (A4070G) polymorphism and RPL. All the
      data acquired from the RPL patients in this experiment illustrate the importance
      of screening thrombophilia. Nevertheless, more studies on large-scale populations
      may be needed to identify novel genetic variants. ABBREVIATIONS: ASRM: American
      Society of Reproductive Medicine; HHCY: hyperhomocysteinemia; MTHFR:
      methylenetetrahydrofolate reductase; PCR: polymerase chain reaction; PAGE: poly
      acrylamide gel electrophoresis; RPL: recurrent pregnancy loss.

PMID- 29658348
TI  - No-Reflow Phenomenon. A New Target for Therapy of Acute Myocardial Infarction
      Independent of Myocardial Infarct Size.

PMID- 29658347
TI  - Contrast enhanced ultrasound (CEUS) imaging of solid benign focal liver lesions.
AB  - INTRODUCTION: Ultrasound is well accepted worldwide for imaging of the liver.
      Absences of radiation exposure, low cost and large diffusion are some of the
      advantages that make this technique the first to be used in the assessment of
      focal liver lesions (FLL). Areas covered: Contrast enhanced ultrasound (CEUS) has
      been introduced more than twenty years ago, and its detection rate is comparable
      to that of contrast enhanced magnetic resonance imaging (CEMRI) and contrast
      enhanced computed tomography (CECT). In this narrative review, we discuss the
      main CEUS features of benign liver lesions and controversies in published results
      including the gold standard chosen and the quality and knowledge of the preferred
      techniques. Expert commentary: CEUS is safe and allows an immediate evaluation of
      the nature of FLL. CEUS permits differentiation between malignant and benign FLL
      in healthy liver parenchyma by analysing the arterial, portal venous and late
      phases. CEMRI and CECT are reliable to characterize FLL but higher costs,
      radiation exposure, nephrotoxicity (in particular for CECT) and absence of real
      time imaging limit the appropriate evaluation of FLL. Therefore CEUS can be
      preferred in most clinical situations, and when results are unclear or suggestive
      for malignant FLL, biopsy and histological examination can be directly initiated
      avoiding unnecessary additional imaging.

PMID- 29658349
TI  - Biodegradable hybrid-structured nanofibrous membrane supported chemoprotective
      gene therapy enhances chemotherapy tolerance and efficacy in malignant glioma
      rats.
AB  - Chemotherapy is ineffective for treating malignant glioma (MG) because of the low
      therapeutic levels of pharmaceuticals in tumour tissues and the well-known tumour
      resistance. The resistance to alkylators is modulated by the DNA repair protein
      O6-alkylguanine-DNA alkyltransferase (AGT). O6-benzylguanine (O6-BG) can
      irreversibly inactivate AGT by competing with O6-methylguanine and has been
      confirmed to increase the therapeutic activity of alkylators. We developed hybrid
      structured poly[(d,l)-lactide-co-glycolide] nanofibrous membranes (HSNMs) that
      enable the sequential and sustained release of O6-BG and two alkylators
      (carmustine and temozolomide [TMZ]). HSNMs were surgically instilled into the
      cerebral cavity of pathogen-free rats and F98 glioma-bearing rats. The release
      behaviours of loaded drugs were quantified by using high-performance liquid
      chromatography. The treatment results were compared with the rats treated with
      intraperitoneal injection of O6-BG combined with surgical implantation of
      carmustine wafer and oral TMZ. The HSNMs revealed a sequential drug release
      behaviour with the elution of high drug concentrations of O6-BG in the early
      phase, followed by high levels of two alkylators. All drug concentrations
      remained high for over 14 weeks. Tumour growth was slower and the mean survival
      time was significantly prolonged in the HSNM-treated group. Biodegradable HSNMs
      can enhance therapeutic efficacy and prevent toxic systemic effects.

PMID- 29658350
TI  - Vascular endothelial growth factor C promotes cervical cancer cell invasiveness
      via regulation of microRNA-326/cortactin expression.
AB  - Vascular endothelial growth factor C (VEGF-C) accelerates cervical cancer
      metastasis, while the detailed mechanism remains largely unknown. Recent evidence
      indicates that microRNA play a crucial role in controlling cancer cell
      invasiveness. In the present study, we investigated the role of miR-326 in VEGF-C
      induced cervical cancer cell invasion. VEGF-C expression was higher and miR-326
      was much lower in primary cervical cancer specimens than that in non-cancerous
      specimens, and a negative correlation between VEGF-C and miR-326 was found. On
      cervical carcinoma cell line SiHa cells, treatment with VEGF-C downregulated miR
      326 level and increased cortactin protein expression. Transfection with miR-326
      mimic reversed cortactin expression induced by VEGF-C, suggesting that VEGF-C
      increased cortactin via downregulation of miR-326. VEGF-C activated c-Src and c
      Src inhibitor PP2 abolished VEGF-C effect on miR-326 and cortactin expression,
      implying that VEGF-C regulated miR-326/cortactin via c-Src signaling. VEGF-C
      promoted SiHa cell invasion index, which was largely inhibited by transfection
      with miR-326 antagonist or by siRNA against cortactin. In conclusion, our
      findings implied that VEGF-C reduced miR-326 expression and increased cortactin
      expression through c-Src signaling, leading to enhanced cervical cancer
      invasiveness. This may shed light on potential therapeutic strategies for
      cervical cancer therapy.

PMID- 29658351
TI  - High estrogen exposure may not be detrimental on endometrial receptivity in women
      with PCOS.
AB  - The study aimed to assess the effect of high estrogen exposure and coasting on
      cycle outcome in women at risk for developing ovarian hyperstimulation syndrome
      (OHSS). Retrospective case-control study was conducted to figure out the outcomes
      of GnRH antagonist cycles in which women were at risk to develop OHSS. Women who
      underwent coasting (n = 100) were compared with a control group of women who did
      not undergo coasting (n = 287). Effect of endometrial estrogen exposure was
      determined by calculating area under curve of temporal estrogen measurements
      (AUCEM) through the cycle. Among 387 women with PCOS, 100 cases were required to
      undergo coasting to avoid OHSS. All participants reached to embryo transfer stage
      and clinical pregnancy rate was 44% in group with coasting whereas 39% in group
      without coasting (p > .05). AUCEM was a significant predictor for the cases who
      required coasting to avoid OHSS (AUC = 0.754, p < .001). Optimal cut off value
      was calculated to be 6762 with 71% sensitivity and 67% specificity. ROC analysis
      showed no predictive value of AUCEM for clinical pregnancy in subgroup of women
      with coasting (AUC = 0.496, p > .05). Consistently, ROC analysis showed no
      predictive value of AUCEM for clinical pregnancy in subgroup of women without
      coasting (AUC = 0.494, p > .05). In conclusion, neither coasting nor the high
      endometrial estrogen exposure was found to have detrimental effect on endometrial
      receptivity and cycle outcome in PCOS.

PMID- 29658352
TI  - Chronic subdural collection overlying an intra-axial hemorrhagic lesion in
      chronic myelomonocytic leukemia: special report and review of the literature.
AB  - INTRODUCTION: Chronic myelomonocytic leukaemia (CMML) is a clonal hematopoietic
      stem cell disorder characterized by the presence of an absolute monocytosis in
      the peripheral blood (>1 x 109/L) and the presence of myelodysplastic and
      myeloproliferative features in the bone marrow. Involvement of the central
      nervous system (CNS) is uncommon in CMML. Areas covered: Herein described is a
      case report of a CMML patient who presents with symptomatic chronic subdural
      collection overlying a haemorrhagic brain lesion, along with diffuse dural
      infiltration, after two cycles of azacytidine. Surgical intervention was
      performed to alleviate the mass effect on the brain, and obtain a tissue sample
      for diagnosis. Histopathological report confirmed brain infiltration with myeloid
      leukemic cells. Expert commentary: Despite its rarity, cerebral dissemination
      should be considered even in patients with CMML. A multidisciplinary approach,
      lead by a hematologist, is mandatory in order to correct the underlying
      haematological disorder, with specific attention to the coagulation profile.
      Surgical intervention is necessary for symptomatic patients, and should be
      performed once an improvement of clinical conditions has been achieved. Despite
      appropriate surgical and medical therapy, the prognosis remains poor with high
      risk of perioperative complications, such as rebleeding, and progressive systemic
      involvement.

PMID- 29658353
TI  - Early initiation of zoledronic acid does not impact bone healing or clinical
      outcomes of hallux valgus orthomorphia.
AB  - Objective This prospective randomized controlled study was performed to determine
      whether early drug use for osteoporosis impacts bone healing after orthomorphic
      surgery for hallux valgus (HV) in menopausal patients with osteoporosis. Methods
      This study included 113 consecutive patients with osteoporosis who underwent a
      combination of Lapidus arthrodesis and Akin osteotomy for treatment of HV. The
      patients were randomly divided into a zoledronic acid (ZOL) group (5-mg
      intravenous injection of ZOL, n = 56) and a placebo group (n = 57); both ZOL and
      placebo were administered 1 week postoperatively. Radiographs were taken
      preoperatively and at 1, 6, 8, 10, and 12 weeks postoperatively to record the
      time of the first tarsometatarsal joint (FTJ) fusion and Akin osteotomy site
      healing. Clinical outcomes were evaluated using the American Orthopedic Foot and
      Ankle Society (AOFAS) scoring system 24 weeks after surgery. Results There were
      no statistically significant differences in the FTJ fusion time after Lapidus
      arthrodesis, healing time after Akin osteotomy, or postoperative AOFAS scores
      between the two groups. Conclusion Early initiation of ZOL does not impact the
      bone healing or clinical outcomes of orthomorphic surgery for HV in
      postmenopausal women diagnosed with osteoporosis after a combination of Lapidus
      arthrodesis and Akin osteotomy.

PMID- 29658354
TI  - Serum chemerin level in women with PCOS and its relation with the risk of
      spontaneous abortion.
AB  - BACKGROUND AND AIM: Insulin resistance (IR) was recognized as a risk factor for
      the occurrence of abortion in patients with polycystic ovary syndrome (PCOS).
      Chemerin was an adipokine which could induce IR and associated with reproductive
      process closely. However, few studies have inquired the relativity between
      chemerin and the occurrence of abortion in patients with PCOS. The aim of this
      study was to evaluate the relationship between serum chemerin and the occurrence
      of abortion in women with PCOS. METHODS: We recruited 198 women with PCOS to
      participate in our study. On the third day of menstrual cycle or a random day in
      women with amenorrhea, we obtained their venous blood and measured the fasting
      insulin, fasting plasma glucose, total cholesterol, high density lipoprotein
      cholesterol, triglyceride, chemerin, and hormones including FSH, E2, P, PRL, LH,
      and T. Additionally, BMI, HOMA-IR and LH/FSH of each subject were calculated.
      Finally, 58 of them were included in the study, in which 30 of them had normal
      pregnancy and the other 28 had an early miscarriage. We compared the biochemical
      characteristics between the normal pregnancy group and abortion group by
      independent-samples t test. RESULTS: In our study, those with a normal pregnancy
      had a lower level of BMI, FINs, HOMA-IR, and chemerin compared to abortion
      patients (p < .05). After adjusted for BMI, only chemerin was associated with the
      occurrence of abortion in PCOS patients (p < .05). CONCLUSIONS: Serum chemerin
      level is associated with the occurrence of abortion in patients with PCOS. Thus,
      serum chemerin may serve as a biomarker to identify pregnant women with PCOS who
      are at particular risk for later abortion, and who may benefit from prevention
      strategies.

PMID- 29658355
TI  - Procalcitonin and albumin as prognostic biomarkers in elderly patients with a
      risk of bacterial infection.
AB  - Aim This study was performed to investigate serum procalcitonin (PCT) and albumin
      (Alb) as prognostic biomarkers in elderly patients at risk of bacterial
      infection. Methods Serum PCT was measured in 270 hospitalized patients (mean age,
      77.4 years) with suspected bacterial infection. The PCT-negative (<0.5 ng/mL) and
      PCT-positive (>=0.5 ng/mL) groups comprised 155 and 115 patients, respectively.
      Logistic regression analysis was performed with various clinical laboratory test
      values as independent variables and PCT positivity/negativity as the dependent
      variable. Results C-reactive protein (CRP) was the only independent variable
      significantly associated with PCT positivity/negativity. In the survival
      analysis, the 30-day in-hospital death rate was significantly higher in the PCT
      positive than -negative group. Within the Alb-positive group (>2.5 g/dL), no
      significant difference in survival was observed between the PCT-positive and 
      negative groups. However, within the Alb-negative group (<=2.5 g/dL), the
      survival rate was significantly lower in the PCT-positive than -negative group.
      PCT was strongly associated with CRP and Alb, and having both PCT positivity and
      Alb negativity was a prognostic factor for elderly people at risk of bacterial
      infection. Conclusions Combined measurement of PCT with Alb is expected to be a
      valuable tool to assess prognosis in elderly people at risk of bacterial
      infection.

PMID- 29658356
TI  - Percutaneous full endoscopic treatment of cystic lymphangioma of cauda equina: a
      case report.
AB  - Intraspinal epidural lymphangioma of cauda equina are extremely rare, only three
      cases have been reported in the past. We report a 63-year-old female with
      lymphangioma at S1-S2 level which was resected under epidural anesthesia using a
      percutaneous full endoscope with no evidence of recurrence at 19 months follow
      up.

PMID- 29658357
TI  - Analysis of clinical data to determine the minimum number of sensors required for
      adequate skin temperature monitoring of superficial hyperthermia treatments.
AB  - PURPOSE: Tumor response and treatment toxicity are related to minimum and maximum
      tissue temperatures during hyperthermia, respectively. Using a large set of
      clinical data, we analyzed the number of sensors required to adequately monitor
      skin temperature during superficial hyperthermia treatment of breast cancer
      patients. METHODS: Hyperthermia treatments monitored with >60 stationary
      temperature sensors were selected from a database of patients with recurrent
      breast cancer treated with re-irradiation (23 * 2 Gy) and hyperthermia using
      single 434 MHz applicators (effective field size 351-396 cm2). Reduced
      temperature monitoring schemes involved randomly selected subsets of stationary
      skin sensors, and another subset simulating continuous thermal mapping of the
      skin. Temperature differences (DeltaT) between subsets and complete sets of
      sensors were evaluated in terms of overall minimum (Tmin) and maximum (Tmax)
      temperature, as well as T90 and T10. RESULTS: Eighty patients were included
      yielding a total of 400 hyperthermia sessions. Median DeltaT was <0.01  degrees C
      for T90, its 95% confidence interval (95%CI) decreased to <=0.5  degrees C when
      >50 sensors were used. Subsets of <10 sensors result in underestimation of Tmax
      up to -2.1  degrees C (DeltaT 95%CI), which decreased to -0.5  degrees C when >50
      sensors were used. Thermal profiles (8-21 probes) yielded a median DeltaT < 0.01 
      degrees C for T90 and Tmax, with a 95%CI of -0.2  degrees C and 0.4  degrees C,
      respectively. The detection rate of Tmax >=43  degrees C is >=85% while using >50
      stationary sensors or thermal profiles. CONCLUSIONS: Adequate coverage of the
      skin temperature distribution during superficial hyperthermia treatment requires
      the use of >50 stationary sensors per 400 cm2 applicator. Thermal mapping is a
      valid alternative.

PMID- 29658358
TI  - Association of MTHFR C677T gene polymorphism with metabolic syndrome in a Chinese
      population: a case-control study.
AB  - Objective To investigate the association of the MTHFR C677T gene polymorphism
      with metabolic syndrome (MetS) in people in Hubei Province, China. Methods A case
      control study was conducted with 651 subjects with MetS (MetS group) and 727
      healthy controls (control group) at Renmin Hospital of Wuhan University between
      January and December 2016. The MTHFR C677T genotype was detected by the gene chip
      technique and clinical data were collected. Results Body mass index, waist
      circumference, the waist-hip-ratio, systolic and diastolic blood pressure,
      fasting blood glucose, fasting insulin, triglyceride, total cholesterol, low
      density lipoprotein-cholesterol, and homocysteine levels, and the homeostasis
      model assessment of insulin resistance were higher in the MetS group than in
      controls. The risk of MetS was higher for the TT genotype and T allele carriers
      than for the CC genotype and C allele carriers. With MetS, the TT genotype
      increased the risk of elevated blood pressure, fasting glucose levels, and
      triglyceride levels. Patients with MetS and the TT genotype showed more severe
      abdominal obesity, dyslipidaemia, insulin resistance, elevated blood pressure,
      elevated fasting glucose levels, and hyperhomocysteinaemia compared with those
      with the CC genotype. Conclusions In this population, MTHFR C677T gene
      polymorphism may be a risk factor for MetS.

PMID- 29658359
TI  - Two new benzophenones and one new natural amide alkaloid isolated from a mangrove
      derived Fungus Penicillium citrinum.
AB  - Two new compounds penibenzophenones A-B (1-2), and the synthetic alpha,beta
      unsaturated amide alkaloid (E)-tert-butyl(3-cinnamamidopropyl)carbamate (4),
      newly identified as a natural product, alone with three known ones (3, 5-6) were
      isolated from the EtOAc extract of the endophytic fungus Penicillium citrinum HL
      5126 isolated from the mangrove Bruguiera sexangula var. rhynchopetala collected
      in the South China Sea. Compound 1 was a chlorinated benzophenone. The structures
      of 1-6 were elucidated by extensive NMR spectral interpretation, MS data and X
      ray analysis. The new compound 2 displayed cytotoxic activity against human A549
      cell lines with an IC50 value of 15.7 MUg/mL, and 1 showed antibacterial activity
      against Staphylococcus aureus with a MIC value of 20 MUg/mL.

PMID- 29658360
TI  - Hyaluronic acid promotes proliferation and migration of human meniscus cells via
      a CD44-dependent mechanism.
AB  - PURPOSE: Treatment of meniscal injury is important for osteoarthritis (OA)
      prevention. Meniscus cells are divided between inner and outer cells, which have
      different characteristics and vascularity. We evaluated the effects of hyaluronic
      acid (HA) on the proliferation and migration of human inner and outer meniscus
      cells, and investigated the underlying healing mechanisms. MATERIALS AND METHODS:
      Lateral menisci from 18 patients who underwent total knee arthroplasty were used.
      Meniscus cells were harvested from the outer and inner menisci and evaluated
      using migration and proliferation assays after treatment with HA or chondroitin
      sulfate (CS). The effects of HA on prostaglandin E2 (PGE2)-induced apoptosis and
      gene expression were evaluated. RESULTS: Cell migration and proliferation were
      increased by HA in a concentration-dependent manner, in both inner and outer
      meniscus cells. PGE2-induced apoptosis and caspase-3/7 activity were suppressed
      by HA in both inner and outer meniscus cells, and these effects were blocked by
      an anti-CD44 antibody. COL2A1 and ACAN mRNA levels were upregulated following HA
      treatment of inner meniscus cells. MMP13 mRNA was downregulated following CS
      stimulation of both inner and outer meniscus cells. These results suggest that CS
      treatment suppresses the inflammatory reaction rather than providing meniscal
      restoration. The phosphatidylinositol 3-kinase (PI3K) and mitogen-activated
      protein kinase (MAPK) pathways were activated by HA in both types of meniscus
      cells; these effects were blocked by treatment with an anti-CD44 antibody.
      CONCLUSIONS: HA promoted human meniscus regeneration by inhibiting apoptosis,
      promoting cell migration, and accelerating cell proliferation, potentially
      through the PI3K/MAPK pathway via the CD44 receptor.

PMID- 29658361
TI  - MyD88 as a therapeutic target for inflammatory lung diseases.
AB  - INTRODUCTION: Myeloid differentiation primary response protein 88 (MyD88) is a
      critical adaptor protein involved in Toll-like and IL-1 receptor family signaling
      controlling innate immune responses and inflammation. Genetic deletion of MyD88
      function results in profound suppression of inflammation and reduced resistance
      of the host to pathogens indicating non-redundant roles of MyD88. The TIR domain
      is critical for MyD88 dimerization and signaling for TLR and IL-1R family
      receptor. Areas covered: Emerging evidence suggests that chemical disruption of
      the TIR domain attenuates cell activation and inhibits in vivo MyD88-dependent
      inflammation. We review the development of MyD88 dimerization disruptors as a
      novel therapeutic approach of respiratory diseases with a focus on COPD. Expert
      opinion: There is a proof of concept that therapeutic targeting of MyD88 is
      feasible and first preclinical data are highly promising. This opens a great
      opportunity to treat exacerbations of COPD and other chronic respiratory
      diseases. However, extensive preclinical investigations and risk analyses are
      required with carefully evaluation of reduced host resistance and opportunistic
      infections.

PMID- 29658362
TI  - Experiences and psychological distress of fertility treatment and employment.
AB  - PURPOSE: This study examined experiences and psychological distress about
      fertility treatment in people combining work and treatment. METHODS: Five hundred
      and sixty-three participants in the UK completed an online survey asking about
      difficulties in combining work and treatment; workplace disclosure, support,
      absence and policy; and psychological distress about treatment. RESULTS: Absence
      from work and perceptions that treatment has an impact on work and career
      prospects were reported by the majority of participants and this was related to
      the psychological distress of treatment. Around three quarters of participants
      disclosed to their employer and colleagues. The key reason for disclosure was
      needing to ask for absence from work and the main reason for non-disclosure was
      privacy. Workplace policy relating to managing fertility treatment and support
      from colleagues and their employer was related to reduced psychological distress
      but workplace policy was reported by less than one quarter of participants.
      CONCLUSION: Difficulties experienced in combining work and treatment suggest that
      support is needed. Specific workplace policy, guidance for supervisors and
      flexibility in fertility clinic times should help support employees during
      treatment and reduce psychological distress, thereby potentially influencing
      physical health and treatment outcomes.

PMID- 29658363
TI  - Therapy of cervical cancer using 131I-labeled nanoparticles.
AB  - Objective To evaluate the effectiveness of two kinds of Arg-Gly-Asp (RGD)
      targeted 131I-containing nanoliposomes for the treatment of cervical cancer in
      vitro and in vivo. Methods The nanoparticle liposomes designated RGD-131I
      tyrosine peptide chain (TPC)-L and 131I-RGD-L were prepared. The emulsion solvent
      evaporation method was used to encapsulate the polypeptide into liposomes. The
      quantity of entrapped polypeptide was measured using UV spectrophotometry. The
      labeling rates, radiochemical purities, and total radioactivities were measured
      using paper chromatography. Cytotoxicity was assessed using the MTS assay and
      flow cytometry. Therapeutic efficacy was monitored using a mouse xenograft model
      of cervical cancer. Results The labeling efficiency, radiochemical purity, and
      specific radioactivity of RGD-131I-TPC-L were greater than those of 131I-RGD-L.
      The cytotoxicity test indicated that late apoptosis of cells treated with RGD
      131I-TPC-L and 131I-RGD-L was higher than that of cells treated with Na131I. The
      therapeutic effect of RGD-131I-TPC-L was better than that of 31I-RGD-L in the
      mouse model. Conclusions The specific activity of liposome-encapsulated RGD-131I
      TPC-L was higher than that of 131I-RGD-L, which labeled liposomes directly.
      Moreover, the RGD-131I-TPC-L liposomes were more effective for killing
      xenografted tumor cells.

PMID- 29658364
TI  - Prognostic value of PIVKA-II in hepatocellular carcinoma patients receiving
      curative ablation: A systematic review and meta-analysis.
AB  - BACKGROUND: Several studies have been conducted to evaluate the prognostic value
      of prothrombin induced by vitamin K absence-II (PIVKA-II) overexpression in
      hepatocellular carcinoma patients treated with curative ablation. However, the
      results remain controversial. The purpose of this meta-analysis was to explore
      the correlation between PIVKA-II expression and survival outcomes in these
      patients. METHODS: We performed a systematic literature search in PubMed, EMBASE,
      Medline, Cochrane Library, and Web of Science to identify the relevant articles
      investigating the prognostic value of PIVKA-II in patients with hepatocellular
      carcinoma. Combined hazard ratios (HR) and their 95% confidence intervals (CI)
      for overall survival and recurrence-free survival were calculated as the analysis
      endpoints. RESULTS: A total of 15 cohorts encompassing 5647 patients were
      included. The results indicated that elevated PIVKA-II was significantly
      associated with poorer overall survival (HR 1.59; 95% CI 1.40, 1.82; P < 0.001)
      and recurrence-free survival (HR 1.76; 95% CI 1.42, 2.17; P < 0.001). Similar
      results were observed in the subgroup analysis based on sample size, analytical
      method, treatment modality, and cut-off value. CONCLUSIONS: This meta-analysis
      suggests that elevated PIVKA-II is a predictor of unfavorable overall survival
      and recurrence-free survival in hepatocellular carcinoma patients receiving
      curative ablation. More rigorous studies are warranted to confirm the clinical
      utility of PIVKA-II in determining hepatocellular carcinoma prognosis.

PMID- 29658365
TI  - Resveratrol delivery by ultrasound-mediated nanobubbles targeting nucleus
      pulposus cells.
AB  - AIM: To improve nucleus pulposus cell-targeted therapy for intervertebral disc
      degeneration (IDD) by fabricating a novel kind of ultrasound (US)-mediated
      poly(lactic-co-glycolic acid) nanobubbles (NBs) as a means of targeted drug
      delivery. MATERIALS & METHODS: The resveratrol (RES)-embedded NBs were
      synthesized using a double-emulsion method. The active NP cell-targeting
      biomarker CDH2 antibody (AbCDH2) was further conjugated to the NBs using a
      carbodiimide method. Then, this RES/AbCDH2 NBs were examined by physical
      properties, specifc cell-targeting ability, anticatabolism effect in vitro and in
      vivo. RESULTS: RES/AbCDH2 NBs exhibited high RES-loading efficiency, and US
      triggered accelerated RES release. Furthermore, RES/AbCDH2 NB treatment exhibited
      excellent anticatabolic ability in vitro; and in an IDD rabbit model, US-mediated
      RES/AbCDH2 NB injection effectively retarded the degenerative process of the
      intervertebral disc in vivo. CONCLUSION: The combination of US irradiation and
      drug delivery through RES/AbCDH2 NBs can be considered as a novel treatment
      option for IDD.

PMID- 29658366
TI  - A novel case using femtosecond laser-acquired lenticule for recurrent pterygium:
      case report and literature review.
AB  - Small incision lenticule extraction (SMILE) is a minimally invasive, safe and
      flapless femtosecond laser technique used mainly to correct myopia through
      extraction of a corneal lenticule. Lenticules obtained in this way are
      transparent and of high quality, and thus, can be used to treat other corneal
      diseases. A 65-year-old male patient presented with recurrent pterygium
      complicated by thin cornea. The patient was treated surgically using a SMILE
      extracted lenticule to avoid further complications and to maintain eyeball
      integrity. The lenticule was sutured over the thin section of cornea using 10-0
      interrupted nylon sutures and enclosed by a single layer of amniotic membrane.
      The patient was evaluated using slit-lamp biomicroscopy and anterior-segment
      optical-coherence tomography. During an 8-month follow-up, the graft remained
      intact with no sign of rejection and corneal thickness was maintained. Tectonic
      keratoplasty using a SMILE-extracted lenticule appears to be a safe, cost
      effective and reliable method for treating thin cornea due to repeated surgeries
      for recurrent pterygium. This is the first case of recurrent pterygium
      complicated by thin cornea managed surgically using a SMILE-extracted lenticule.

PMID- 29658367
TI  - The evolution of graduate medical education over the past decade: Building a new
      pediatric residency program in an era of innovation.
AB  - AIM: In 2011, Johns Hopkins Medicine integrated with All Children's Hospital in
      St. Petersburg Florida to create an academic campus nearly 1000 miles from
      Baltimore. In 2014, the newly named Johns Hopkins All Children's Hospital
      established a new pediatric residency program. At that time, the Association for
      Graduate Medical Education had not accredited a new pediatric program in the USA
      in over 10 years. METHODS: A unique set of circumstances provided an opportunity
      for program developers to build the residency under newly identified core tenets
      to create a number of innovative features targeted to address the many calls for
      change in graduate medical education. RESULTS: This paper focuses on three of
      those innovations and demonstrates how they address the many challenges
      introduced by the changing landscape of graduate medical education. CONCLUSION:
      Although a full evaluation of our program is only possible after many years, this
      article presents the core tenets which guided curricular development and
      discusses our experiences thus far. We provide lessons learned for programs
      considering similar innovations.

PMID- 29658368
TI  - The AAA + ATPase Thorase is neuroprotective against ischemic injury.
AB  - Neuronal preconditioning in vitro or in vivo with a stressful but non-lethal
      stimulus leads to new protein expression that mediates a profound neuroprotection
      against glutamate excitotoxicity and experimental stroke. The proteins that
      mediate neuroprotection are relatively unknown and under discovery. Here we find
      that the expression of the AAA + ATPase Thorase is induced by preconditioning
      stimulation both in vitro and in vivo. Thorase provides neuroprotection in an ATP
      dependent manner against oxygen-glucose deprivation (OGD) neurotoxicity or
      glutamate N-Methyl-D-aspartate (NMDA) receptor-mediated excitotoxicity in vitro.
      Knock-down of Thorase prevents the establishment of preconditioning induced
      neuroprotection against OGD or NMDA neurotoxicity. Transgenic overexpression of
      Thorase provides neuroprotection in vivo against middle cerebral artery occlusion
      (MCAO)-induced stroke in mice, while genetic deletion of Thorase results in
      increased injury in vivo following stroke. These results define Thorase as a
      neuroprotective protein and understanding Thorase signaling could offer a new
      therapeutic strategy for the treatment of neurologic disorders.

PMID- 29658369
TI  - Hepatoprotective effect of chiisanoside against acetaminophen-induced acute liver
      injury in mice.
AB  - This study was designed to investigate the hepatoprotective effect of
      chiisanoside (CSS) and its possible mechanisms on acetaminophen (APAP)-induced
      acute liver damage in mice. The serum activities of alanine transaminase (ALT),
      aspartate transaminase (AST), tumor necrosis factor alpha (TNF-alpha),
      interleukin-1 beta (IL-1beta), interleukin-6 (IL-6), and the hepatic levels of
      superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and malondialdehyde
      (MDA) were determined using the commercially available assay kits. The hepatic
      mRNA levels were measured by RT-PCR. The hepatic protein expressions of nuclear
      factor-kappa B (NF-kappaB), MAPK and their phosphorylated isoforms were evaluated
      by western blot assays. The results indicated that CSS (240 mg/kg) exhibited the
      hepatoprotective effects by inhibiting oxidative stress and inflammation on APAP
      induced acute liver injury. Furthermore, the anti-inflammatory activity of CSS is
      largely related to the regulation of the NF-kappaB and MAPKs signaling pathways.
      These findings suggested that CSS possessed hepatoprotective effect against APAP
      induced hepatotoxicity in mice.

PMID- 29658370
TI  - Changes in endothelial function, arterial stiffness and blood pressure in
      pregnant women after consumption of high-flavanol and high-theobromine chocolate:
      a double blind randomized clinical trial.
AB  - OBJECTIVES: The aim of this 2-group, parallel, double blind single-centre RCT was
      to evaluate the acute and chronic impacts of high flavanol high theobromine
      (HFHT) chocolate consumption on endothelial function, arterial stiffness and
      blood pressure (BP) in women at risk of preeclampsia. METHODS: 131 pregnant women
      considered at risk of preeclampsia based on uterine artery Doppler ultrasound
      were divided into two groups (HFHT or low flavanol and theobromine chocolate
      (LFLT). Acute changes in plasma flavanol and theobromine, peripheral arterial
      tonometry and BP were evaluated at randomization (0, 60 and 120 min after a
      single 40-g dose of chocolate) and again 6 and 12 weeks after daily 30-g
      chocolate intake. The EndoPAT 2000 provided reactive hyperemia index (RHI) and
      adjusted augmentation index (AIx) as markers for endothelial function and
      arterial stiffness, respectively. RESULTS: Compared with LFLT, acute HFHT intake
      significantly increased plasma epicatechin and theobromine (p < 0.0001),
      decreased AIx (p < 0.0001) and increased diastolic BP (3.49 +/- 3.40 mmHg
      increase in HFHT group vs 1.55 +/- 2.59 mmHg increase in LFLT group, p = 0.0008).
      Chronic HFHT compared with LFLT intake significantly increased plasma theobromine
      (p < 0.0001). No other significant within group or between group changes were
      observed. CONCLUSIONS: Acute consumption of HFHT, compared to LFLT, increased
      plasma epicatechin and theobromine concentrations and decreased arterial
      stiffness, with no effect on endothelial function and a marginal increase in
      diastolic BP. Chronic HFHT intake increased plasma theobromine, though it did not
      have positive impacts on endothelial function, arterial stiffness or BP when
      compared to LFLT in pregnant women at risk of PE.

PMID- 29658371
TI  - Physician Consultations, Prostate Cancer Knowledge, and PSA Screening of African
      American Men in the Era of Shared Decision-Making.
AB  - African American (AA)/Black men are more likely to develop aggressive prostate
      cancer (PCa), yet less likely to be screened despite guidelines espousing shared
      decision-making regarding PCa screening and prostate-specific antigen (PSA)
      testing. Given the documented racial disparities in PCa incidence and mortality,
      engaging interactions with physicians are especially important for AA/Black men.
      Thus, this study evaluated occurrence of physician-patient conversations among
      AA/Black men, and whether such conversations were associated with PCa knowledge.
      We also quantified the serum PSA values of participants who had, and had not,
      discussed testing with their physicians. Self-identified AA/Black men living in
      California and New York, ages 21-85, donated blood and completed a comprehensive
      sociodemographic and health survey ( n = 414). Less than half (45.2%) of
      participants had discussed PCa screening with their physicians. Multivariate
      analyses were used to assess whether physician-patient conversations predicted
      PCa knowledge after adjusting for key sociodemographic/economic and health-care
      variables. Increased PCa knowledge was correlated with younger age, higher income
      and education, and having discussed the pros and cons of PCa testing with a
      physician. Serum PSA values were measured by ELISA. Higher-than-normal PSA values
      were found in 38.5% of men who had discussed PCa screening with a physician and
      29.1% who had not discussed PCa screening. Our results suggest that physician
      AA/Black patient conversations regarding PCa risk need improvement. Encouraging
      more effective communication between physicians and AA/Black men concerning PCa
      screening and PSA testing has the potential to reduce PCa health disparities.

PMID- 29658373
TI  - Talking emotions: vowel selection in fictional names depends on the emotional
      valence of the to-be-named faces and objects.
AB  - One prestudy based on a corpus analysis and four experiments in which
      participants had to invent novel names for persons or objects (N = 336
      participants in total) investigated how the valence of a face or an object
      affects the phonological characteristics of the respective novel name. Based on
      the articulatory feedback hypothesis, we predicted that /i:/ is included more
      frequently in fictional names for faces or objects with a positive valence than
      for those with a negative valence. For /o:/, the pattern should reverse. An
      analysis of the Berlin Affective Word List - Reloaded (BAWL-R) yielded a higher
      number of occurrences of /o:/ in German words with negative valence than in words
      with positive valence; with /i:/ the situation is less clear. In Experiments 1
      and 2, participants named persons showing a positive or a negative facial
      expression. Names for smiling persons included more /i:/s and fewer /o:/s than
      names for persons with a negative facial expression. In Experiments 3 and 4,
      participants heard a Swahili narration and invented pseudo-Swahili names for
      objects with positive, neutral, or negative valence. Names for positive objects
      included more /i:/s than names for neutral or negative objects, and names for
      negative objects included more /o:/s than names for neutral or positive objects.
      These finding indicate a stable vowel-emotion link.

PMID- 29658372
TI  - MiR-340 affects gastric cancer cell proliferation, cycle, and apoptosis through
      regulating SOCS3/JAK-STAT signaling pathway.
AB  - OBJECTIVE: Janus kinase (JAK)-signal transducer and activator of transcription
      (STAT) signaling pathway is closely related to tumorigenesis. Suppressors of
      cytokine signaling 3 (SOCS3) is a negative regulator of JAK-STAT signaling
      pathway. MiR-340 expression is significantly upregulated in gastric cancer (GC)
      tissue. This study investigated the role of miR-340 in regulating SOCS3
      expression and affecting GC cell proliferation, cycle, and apoptosis. PATIENTS
      AND METHODS: Dual luciferase assay was used to verify the targeted relationship
      between miR-340 and SOCS3. GC tissue was collected from patients. Normal gastric
      mucosal tissue was selected as control. MiR-340, SOCS3, p-JAK, p-STAT3, and
      Survivin protein expressions were compared with GES-1 and MKN-28 cells. MKN-28
      cells were cultured in vitro and divided into four groups, including miR-NC, anti
      miR-340, pSicoR-Blank, and pSicoR-SOCS3 groups. Cell proliferation, cycle, and
      apoptosis were detected by flow cytometry. RESULTS: Bioinformatics analysis
      revealed the targeted relationship between miR-340 and the 3'-UTR of SOCS3 mRNA.
      Dual luciferase assay demonstrated that miR-340 regulated SOCS3 expression. MiR
      340 level was significantly elevated, while SOCS3 level was obviously declined in
      GC tissue compared with normal mucosal tissue. MiR-340, p-JAK, p-STAT3, and
      Survivin expressions were upregulated, whereas SOCS3 expression was reduced in
      MKN-28 cells compared with that in GES-1 cells. Anti-miR-340 or pSicoR-SOCS3
      transfection markedly increased SOCS3 expression, reduced p-JAK, p-STAT3, and
      Survivin levels, attenuated cell proliferation, arrested cell cycle, and enhanced
      cell apoptosis in MKN-28 cells. CONCLUSIONS: Downregulation of miR-340 inhibited
      GC cell proliferation, arrested cell cycle, and facilitated apoptosis through
      upregulating SOCS3 expression to suppress JAK-STAT3 signaling pathway.

PMID- 29658374
TI  - Hypercalcemic crisis in third trimenon: evaluating the optimal treatment
      strategy.
AB  - Hypercalcemia due to primary hyperparathyroidism during pregnancy is a rare
      condition and associated with increased morbidity and mortality for the mother
      and the unborn child. Whereas parathyroidectomy is favored during the second
      trimester, no clear recommendations exist for its management during the third
      trimenon. We here report the case of a 26-year-old woman in the 29th week of her
      first pregnancy, who was admitted to our clinic with hypertension, intra-uterine
      growth retardation and polyhydramnios. Severe hypercalcemia due to primary
      hyperparathyroidism was diagnosed (total calcium 3.34 mmol/l; PTH 216 pg/ml), but
      no enlarged parathyroid gland could be localized by ultrasound. Treatment with
      calcitonin and cinacalcet could not control hypercalcemia. Therefore explorative
      surgery was performed and a single parathyroid adenoma was resected, resulting in
      normalization of serum calcium levels. The surgical procedure was tolerated well
      by the mother and fetus. Hypercalcemia-induced hypertension and polyhydramnios
      ameliorated before C-section was performed two weeks later and unrelated to the
      intervention. This case report underlines the importance of early diagnosis and
      treatment of primary hyperparathyroidism during pregnancy. If diagnosed in the
      third trimenon, an interdisciplinary approach is crucial. If medical treatment
      fails to sufficiently control hypercalcemia, surgical parathyroid exploration
      should be considered even in cases of unsuccessful localization of adenomatous
      parathyroid glands.

PMID- 29658375
TI  - Pharmacokinetic alterations in poloxamer 407-induced hyperlipidemic rats.
AB  - 1. Plasma lipid profile abnormalities in hyperlipidemia can potentially alter the
      pharmacokinetics of a drug in a complex manner. To evaluate these pharmacokinetic
      alterations in hyperlipidemia and to determine the underlying mechanism(s),
      poloxamer 407-induced hyperlipidemic rats (HL rats), a well-established animal
      model of hyperlipidemia have been used. 2. In this review, we summarize findings
      on the pathophysiological and gene expression changes in drug-metabolizing
      enzymes and transporters in HL rats. We discuss pharmacokinetic changes in drugs
      metabolized primarily via hepatic cytochrome P450 (CYPs) in terms of alterations
      in hepatic intrinsic clearance (CL'int), free fraction in plasma (fu) and hepatic
      blood flow rate (QH), depending on the hepatic excretion ratio, as well as drugs
      eliminated primarily by mechanisms other than hepatic CYPs. 3. For lipoprotein
      bound drugs, increased binding to lipoproteins resulted in lower fu values and
      volumes of distribution, with some exceptions. Generally, slower non-renal
      clearance (or total body clearance) of drugs that are substrates of hepatic CYP3A
      and CYP2C is well explained by the following factors: alterations in CL'int (due
      to down-regulation of hepatic CYPs), decreased fu and/or possible decreased QH.
      4. These consistent findings across studies in HL rats suggest more studies are
      needed at the clinical level for optimal pharmacotherapies for hyperlipidemia.

PMID- 29658376
TI  - A leftward perceptual asymmetry when judging the attractiveness of visual
      patterns.
AB  - Perceptual judgements concerning the magnitude of a stimulus feature are
      typically influenced more by the left side of the stimulus than by the right
      side. This research examined whether the leftward bias also applies to judgements
      of the attractiveness of abstract visual patterns. Across four experiments
      participants chose between two versions of a stimulus which either had an
      attractive left side or an attractive right side. Experiments 1 and 2 presented
      artworks and experiments 3 and 4 presented wallpaper designs. In each experiment
      participants showed a significant bias to choose the stimulus with an attractive
      left side more than the stimulus with an attractive right side. The leftward bias
      emerged at age 10/11, was not caused by a systematic asymmetry in the perception
      of colourfulness or complexity, and was stronger when the difference in
      attractiveness between the left and right sides was larger. The results are
      relevant to the aesthetics of product and packaging design and show that leftward
      biases extend to the perceptual judgement of everyday items. Possible causes of
      the leftward bias for attractiveness judgements are discussed and it is suggested
      that the size of the bias may not be a measure of the degree of hemispheric
      specialization.

PMID- 29658377
TI  - The Use of the Newest Vital Sign Health Literacy Instrument in Adolescents With
      Sickle Cell Disease.
AB  - The purpose of this article is to discuss the use of the Newest Vital Sign (NVS)
      health literacy instrument in adolescents with sickle cell disease. The NVS
      evaluates both literacy and numeracy (the ability to understand and work with
      numbers) as well as the ability to locate and apply information. It is important
      to validate the NVS for use in adolescents, as the only currently validated
      instrument, the Rapid Estimate of Adolescent Literacy in Medicine-Teen (REALM
      Teen), does not measure numeracy or the ability to locate or apply information.
      This cross-sectional, descriptive, exploratory correlational study included
      appraisal of data from completion of the REALM-Teen and NVS instruments by a
      convenience sample of 75 adolescents with sickle cell disease. The mean age of
      this study sample was 14.7 years ( SD = 2.2). The mean grade level of
      participants was 8.7 ( SD = 2.2). Internal consistency for the NVS in this
      population was acceptable (alpha = .63). Criterion validity was based on
      correlations between raw scores on the NVS and raw scores on the REALM-Teen.
      There was a significant moderate, positive correlation between NVS and REALM-Teen
      scores ( r = .38, p < .01), demonstrating good criterion validity. Preliminary
      evidence for reliability and validity of the NVS in this population was
      established.

PMID- 29658378
TI  - Improvement of depressive symptoms in patients with moderate-to-severe psoriasis
      treated with ustekinumab: an open label trial validated using beck depression
      inventory, Hamilton depression rating scale measures and 18fluorodeoxyglucose
      (FDG) positron emission tomography (PET).
AB  - BACKGROUND: Psoriasis is a chronic skin disease associated with psychiatric co
      morbidities, especially depression. Early detection of psychological
      vulnerability in patients with psoriasis seems to be of great clinical importance
      and significantly impacts the quality of life of the patients. OBJECTIVES: We
      sought to clarify the association between psoriasis and depressive symptoms in
      patients with moderate-to-severe psoriasis, and to determine the risk factors for
      depressive symptoms and analyze the effect of ustekinumab on the symptoms. We
      also aimed to evaluate the changes in glucose metabolism using
      18fluorodeoxyglucose (FDG) positron emission tomography (FDG-PET). METHODS:
      Fifteen patients with moderate-to-severe psoriasis scheduled to be treated with
      ustekinumab were enrolled. At baseline and after achieving a 75% reduction in the
      Psoriasis Area and Severity Index (PASI) score (PASI75), all patients underwent a
      psychiatric interview and FDG-PET. Fifteen healthy volunteers were enrolled for
      comparison. RESULTS: Patients with moderate-to-severe psoriasis were more
      depressed than those in the control group were (p < .05). The severity of
      psoriasis at baseline did not correlate with the depression symptoms. Treatment
      with ustekinumab significantly reduced the depressive symptoms, as verified using
      Beck Depression Inventory and Hamilton Depression Rating Scale psychiatric
      interviews (p < .05). However, FDG-PET of the brain showed no significant
      difference before and after PASI75 achievement using ustekinumab injection.
      CONCLUSIONS: Patients with moderate-to-severe psoriasis are at an increased risk
      for depressive symptoms, and treatment with ustekinumab may be beneficial. FDG
      PET does not reflect the changes in depressive symptoms in such patients.

PMID- 29658379
TI  - Letters about Published Papers.

PMID- 29658380
TI  - Genetic diversity and population genetic structure of the only population of
      Aoluguya Reindeer (Rangifer tarandus) in China.
AB  - Aoluguya Reindeer is the only reindeer species in China and currently
      approximately 1000 Aoluguya Reindeer remain semi-domesticated. A relative low
      diversity estimate was found by investigating genetic variability and demographic
      history of its population. Mismatch distribution curve of its nucleotide
      sequences and neutral test indicate its population has not experienced expansion.
      Genetic diversity and population structure were also analysed by using its mtDNA
      and microsatellites technology. Statistical results of these analyses showed
      there were varying degrees of population inbreeding and suggested that gene flow
      existed among its populations at one time. Three mutation models were also used
      to detect the bottleneck effect of reindeer population. The genetic variation of
      eight populations is relatively small. In addition, the clustering program
      STRUCTURE was used to analyse Aoluguya Reindeer population structure, to
      determine its optimal K and first time to analyse the phylogenetic status of
      Aoluguya Reindeer among other reindeer subspecies. It is recommended that the
      government establish a natural conservation area in Aoluguya Reindeer growing
      geography, forbade the trade and hunting of Aoluguya Reindeer, and strengthen the
      protection of this endangered species.

PMID- 29658382
TI  - The impact of digital technologies on point-of-care diagnostics in resource
      limited settings.
AB  - INTRODUCTION: Simple, rapid tests that can be used at the point-of-care (POC) can
      improve access to diagnostic services and overall patient management in resource
      limited settings where laboratory infrastructure is limited. Implementation of
      POC tests places tremendous strain on already fragile health systems as the
      demand for training, supply management and quality assurance are amplified.
      Digital health has a major role to play in ensuring effective delivery and
      management of POC testing services. Area covered: The ability to digitise
      laboratory and POC platforms, including lateral flow rapid diagnostic test
      results, can standardize the interpretation of results and allows data to be
      linked to proficiency testing to ensure testing quality, reducing interpretation
      and transcription errors. Remote monitoring of POC instrument functionality and
      utilization through connectivity, allows programs to optimize instrument
      placement, algorithm adoption and supply management. Alerts can be built into the
      system to raise alarm at unusual trends such as outbreaks. Expert commentary:
      Digital technology has had a powerful impact on POC testing in resource limited
      settings. Technology, markets, and medical devices have matured to enable
      connected diagnostics to become a useful tool for epidemiology, patient care and
      tracking, research, and antimicrobial resistance and outbreak surveillance.
      However, to unlock this potential, digital tools must first add value at the
      point of patient care. The global health community need to propose models for
      protecting intellectual property to foster innovation and for safeguarding data
      confidentiality.

PMID- 29658383
TI  - Comparison of the cost-effectiveness of biologic drugs used for moderate-to
      severe psoriasis treatment in the United States.
AB  - PURPOSE: To compare the cost-effectiveness of the newly approved biologic drug,
      brodalumab, with other commonly used biologics for the treatment of moderate-to
      severe psoriasis in the United States. METHODS: An economic model was constructed
      in Excel to compare average costs to achieve Psoriasis Area and Severity Index
      (PASI) 75, 90 and 100 among moderate-to-severe psoriasis patients treated with
      biologics. Total annual costs to health plans associated with treatment with five
      different biologics were estimated and cost-effectiveness compared using the
      estimated average cost per PASI 75, PASI 90 and PASI 100. RESULTS: Total annual
      costs to a health plan per patient with adalimumab, brodalumab, ixekizumab,
      secukinumab and ustekinumab were estimated at $51,246, $38,538, $65,484, $57,510
      and $57,013. Mean annual treatment costs per PASI 75, 90 and 100 were the lowest
      for brodalumab, with the annual cost per PASI 75 for brodalumab, adalimumab,
      ixekizumab, secukinumab and ustekinumab estimated at $48,782, $82,655, $77,957,
      $75,671 and $87,243, per PASI 90 at $51,383, $119,178, $94,904, $108,509 and
      $130,615, and per PASI 100 at $87,585, $284,702, $176,983, $205,393, and
      $366,645. CONCLUSIONS: Brodalumab, which had the lowest drug cost and high drug
      efficacy, was associated with the lowest cost per PASI 75, 90 and 100 among the
      biologics evaluated.

PMID- 29658381
TI  - Hydrogen peroxide: a potent inducer of differentiation of human adipose-derived
      stem cells into chondrocytes.
AB  - Common protocols for chondrogenic differentiation of adipose-derived mesenchymal
      stem cells (ADSCs) are generally expensive and time-consuming and, so far, have
      not successfully recreated pure chondrocytes. We hypothesise that a low level of
      H2O2 may induce differentiation of ADSCs into chondrocytes in a shorter
      incubation time and relatively lower cost. Therefore, this study aimed to
      comparatively investigate the effectiveness of H2O2-containing or free medium in
      the induction of ADSCs to chondrocytes. ADSCs were isolated from the lipoaspirate
      of four healthy females and evaluated by immunophenotyping for their CD90, CD73,
      CD44, CD34, and CD45 cell surface markers. Chondrogenic differentiation was
      carried out using differentiation medium in the presence or absence of 10 and 50
      uM H2O2 in normal and three-dimensional culture system. The intracellular
      contents of reactive oxygen species (ROS) were detected by flow cytometry and
      fluorescence microscopy. The hydroxyproline, was assessed as marker of collagen
      and the glycosaminoglycans (GAGs) content was both qualitatively detected and
      quantitatively determined. Real-time PCR was performed to determine the gene
      expression level of aggrecan (ACAN), type-II collagen, and transcription factor
      Sox9. H2O2-treated cells showed pre-chondrocyte morphology on day 1 and
      chondrocyte pellets were formed on day 14. H2O2-treated cells induced greater
      pellet sizes and showed significantly higher content of GAGs and hydroxyproline
      level compared with untreated cells. The gene expression levels of ACAN, collagen
      type-II, and Sox9 were markedly upregulated by H2O2. Our findings showed for the
      first time that H2O2-containing differentiation medium is potentially more
      effective than H2O2-free differentiation medium in the induction of chondrogensis
      of ADSCs.

PMID- 29658384
TI  - Complications of adult-onset Still's disease and their management.
AB  - INTRODUCTION: Adult-onset Still's disease (AOSD) is a rare systemic auto
      inflammatory disorder in which management and treatment have considerably
      progressed over the past decade. Despite wide use of interleukin (IL)-1 or IL-6
      inhibitors, serious complications remain possible. Areas covered: A comprehensive
      literature search in MEDLINE via Pubmed was performed to review AOSD's severe and
      sometimes life-threatening complications: reactive hemophagocytic
      lymphohystiocytosis, coagulation disorders, fulminant hepatitis, cardiac or
      pulmonary complications and amyloid A amyloidosis. Expert commentary: Early
      recognition and prompt management is essential to significantly decrease morbi
      mortality. The key question is to determine whether the complication is related
      to the disease itself or related to or favored by (e.g. infection) the ongoing
      treatment. For all severe AOSD-related complications, high-dose corticosteroids
      and supportive measures remain the first-line treatment. In case of inadequate
      response, combination with IL-1 or IL-6 blockers is justified. Cyclosporine A and
      etoposide remain of interest, especially in case of reactive hemophagocytic
      lymphohysitocytosis. Plasma exchange may be useful in case of thrombotic
      microangiopathy. In the near future, new biologic or non-biologic drugs targeting
      IL-18 or other cytokines or kinases could be of help.

PMID- 29658385
TI  - Toxicity of mixtures of zinc oxide and graphene oxide nanoparticles to aquatic
      organisms of different trophic level: particles outperform dissolved ions.
AB  - Concomitant releases of various engineered nanoparticles (NPs) into the
      environment have resulted in concerns regarding their combined toxicity to
      aquatic organisms. It is however, still elusive to distinguish the contribution
      to toxicity of components in NP mixtures. In the present study, we quantitatively
      evaluated the relative contribution of NPs in their particulate form
      (NP(particle)) and of dissolved ions released from NPs (NP(ion)) to the combined
      toxicity of binary mixtures of ZnO NPs and graphene oxide nanoplatelets (GO NPs)
      to three aquatic organisms of different trophic levels, including an alga species
      (Scenedesmus obliquus), a cladoceran species (Daphnia magna), and a freshwater
      fish larva (Danio rerio). Our results revealed that the effects of ZnO NPs and GO
      NPs were additive to S. obliquus and D. magna but antagonistic to D. rerio. The
      relative contribution to toxicity (RCT) of the mixture components to S. obliquus
      decreased in the order of RCTGO NP(particle) > RCTZnO NP(particle) > RCTZnO
      NP(ion), while the RCT of the mixture components to D. magna and D. rerio
      decreased in the order of RCTZnO NP(particle) > RCTGO NP(particle) > RCTZnO
      NP(ion). This finding also implies that the suspended particles rather than the
      dissolved Zn-ions dictated the combined toxicity of binary mixtures of ZnO NPs
      and GO NPs to the aquatic organisms of different trophic level. The alleviation
      of the contribution to toxicity of the ionic form of ZnO NPs was caused by the
      adsorption of the dissolved ions on GO NPs. Furthermore, the ZnO NP(particle) and
      GO NP(particle) displayed a different contribution to the observed mixture
      toxicity, dependent on the trophic level of the aquatic organisms tested. The
      difference of the contributions between the two particulate forms was mainly
      associated with differences in the intracellular accumulation of reactive oxygen
      species. Our findings highlight the important role of particles in the ecological
      impact of multi-nanomaterial systems.

PMID- 29658386
TI  - Finite element evaluation of the newest ISO testing standard for polyethylene
      total knee replacement liners.
AB  - Current treatment for end-stage osteoarthritis is total knee replacement. Given
      that the number of total knee replacement surgeries is expected to approach 3.48
      million by 2030, understanding long-term failure is important. One of the
      preclinical tests for total knee replacements is carried out using mechanical
      wear testing under generic walking conditions. Used for this purpose is the
      International Standards Organization's generic walking profile. Recently this
      standard was updated by reversing the direction of anterior/posterior translation
      and internal/external rotation. The effects of this change have not been
      investigated, and therefore, it is unknown if comparisons between wear tests
      utilizing the old and new version of the standard are valid. In this study, we
      used a finite element model along with a frictional energy-based wear model to
      compare the kinematic inputs, contact conditions, and wear from the older and
      newer versions of the ISO standard. Simulator-tested components were used to
      validate the computational model. We found that there were no visible
      similarities in the contact conditions between the old and new versions of the
      standard. The new version of the standard had a lower wear rate but covered a
      larger portion of the articular surface. Locations of wear also varied
      considerably. The results of the study suggest that major differences between the
      old and new standard exist, and therefore, historical wear results should be
      compared with caution to newly obtained results.

PMID- 29658388
TI  - Prostate Cancer Screening Perception, Beliefs, and Practices Among Men in
      Bamenda, Cameroon.
AB  - Prostate Cancer (CaP) is the most commonly diagnosed cancer among Cameroonian
      men. Due to inadequate infrastructure, record keeping, and resources, little is
      known about its true burden on the population. There are rural/urban disparities
      with regards to awareness, screening, treatment, and survivorship. Furthermore,
      use of traditional medicine and homeopathic remedies is widespread, and some men
      delay seeking conventional medical treatment until advanced stages of CaP. This
      study examined the perceptions, beliefs, and practices of men in Cameroon
      regarding late stage CaP diagnoses; identified factors that influence screening
      decision; and ascertained how men decided between traditional or conventional
      medicine for CaP diagnosis and treatment. Semistructured focus groups were used
      to collect data from men in Bamenda, Cameroon. Qualitative data analysis was used
      to analyze transcripts for emerging themes and constructs using a socio
      ecological framework. Twenty-five men participated in the study, with an average
      age of 59. Most of the participants had never received a prostate screening
      recommendation. Socioeconomic status, local beliefs, knowledge levels, awareness
      of CaP and screening methods, and stigma were prominent themes. A significant
      number of Cameroonian men receive late stage CaP diagnosis due to lack of
      awareness, attitudes, cultural beliefs, self-medication, and economic limitation.
      To effectively address these contributing factors to late stage CaP diagnosis, a
      contextually based health education program is warranted and should be tailored
      to fill knowledge gaps about the disease, dispel misconceptions, and focus on
      reducing barriers to utilization of health services.

PMID- 29658387
TI  - Identification of avian vasotocin receptor subtype-specific antagonists involved
      in the stress response of the chicken, Gallus gallus.
AB  - Vasotocin 1a and 1b receptors (V1aR and V1bR) have been shown to play important
      roles in the neuroendocrine regulation of stress responses via the anterior
      pituitary (AP) of birds. To identify effective subtype-specific antagonists for
      the chicken V1aR (cV1aR) and cV1bR, potential antagonists to the mammalian V1R
      were screened against the cV1aR and cV1bR 3D structural models by molecular
      docking analysis with determination of binding pocket/amino acid residues
      involved in the interaction. The antagonistic effects of the selected ligands
      were examined by measuring pro-opiomelanocortin (POMC) heteronuclear RNA (hnPOMC)
      levels following the in vitro stress administration to primary chicken AP cells.
      Results of in silico analysis showed that the Manning compound and several other
      antagonists were bound to cV1bR with higher affinity than the natural agonist,
      arginine vasotocin (AVT). Similarities and differences in the antagonist-receptor
      binding interface with receptors were characterized for each ligand. Non-peptide
      mammalian V1bR antagonists, SSR-149415 and L-368899, were shown to be effective
      and had an additive effect in blocking POMC hnRNA expression in pituitary cell
      culture studies. SR-49059 antagonized the effect(s) of AVT/CRH on the
      downregulation of the cV1aR and the upregulation of the cCRH-R2 expression but
      not the cV1bR and cCRH-R1. The Manning compound antagonized the downregulation of
      cV1aR, cV1bR and cCRH-R1 and the upregulation of cCRH-R2 expression. The
      specificity of antagonists apparently resulted from unique differences in the
      interacting residues and their binding affinities. Collectively, these results
      provide valuable leads for future development of novel compounds capable of
      blocking or attenuating the AP stress response of avian species and perhaps other
      non-mammalian vertebrates as well.

PMID- 29658389
TI  - Comparison of endoscopic-assisted and temporary keratoprosthesis-assisted
      vitrectomy in combat ocular trauma: experience at a tertiary eye center in
      Turkey.
AB  - Objective This study was performed to compare the functional and anatomical
      results of endoscopic-assisted and temporary keratoprosthesis (TKP)-assisted
      vitrectomy in patients with combat ocular trauma (COT). Methods The medical
      records of 14 severely injured eyes of 12 patients who underwent endoscopy or TKP
      implantation in combination with vitreoretinal surgery from 2007 to 2015 were
      retrospectively evaluated. The patients' ocular history and functional and
      anatomic anterior and posterior segment results were analyzed. Results Eight eyes
      (57%) underwent TKP-assisted vitrectomy and six eyes (43%) underwent endoscopic
      vitrectomy. The most common cause of COT was detonation of improvised explosive
      devices (72%), and the most common type of injury was an intraocular foreign body
      (50%). The median time from trauma to surgery and the median surgical time were
      significantly shorter in the endoscopy than TKP group. The postoperative
      functional and anatomical results were not significantly different between the
      two groups. Conclusions TKP-assisted vitrectomy should be performed in eyes
      requiring extensive bimanual surgery. In such cases, a corneal graft must be
      preserved for the TKP at the end of the surgery. Endoscopy shortens the surgical
      time and can reduce the complication rate.

PMID- 29658390
TI  - Spontaneous single nucleotide polymorphism in porcine microRNA-378 seed region
      leads to functional alteration.
AB  - Sequence variation in a microRNA (miRNA) seed region can influence its biogenesis
      and effects on target mRNAs; however, in mammals, few seed region mutations
      leading to functional alterations have been reported to date. Here, we report the
      identification of a single nucleotide polymorphism (SNP) with functional
      consequence located in the seed region of porcine miR-378. In vitro analysis of
      this rs331295049 A17G SNP showed significantly up-regulated expression of the
      mature miR-378 (miR-378/G). In silico target prediction indicated that the SNP
      would modulate secondary structure and result in functional loss affecting >85%
      of the known target genes of the wild-type miR-378 (miR-378/A), and functional
      gain affecting >700 new target genes, and dual-luciferase reporter assay verified
      this result. This report of a SNP in the seed region of miR-378 leads to
      functional alteration and indicates the potential for substantive functional
      consequences to the molecular physiology of a mammalian organism.

PMID- 29658391
TI  - TGFbeta1 Promotes Breast Cancer Local Invasion and Liver Metastasis by Increasing
      the CD44high/CD24- Subpopulation.
AB  - OBJECTIVE: Previous studies have shown that the transforming growth factor beta1
      pathway plays an important role in breast cancer metastasis to the liver.
      However, the mechanism of this metastasis has not been fully clarified. Cancer
      stem cells are essential for the initiation and propagation of tumor metastasis.
      The objective of our current study was to define the role of cancer stem cells in
      transforming growth factor beta1-mediated breast cancer hepatic metastases.
      METHOD: Hematoxylin and eosin staining was used to assess the formation of breast
      cancer liver metastases and local invasion. Cancer stem cells surface markers
      (CD44, CD24, and Epithelial cell adhesion molecule [EpCAM]), luminal/mesenchymal
      markers (keratin8 and alpha smooth muscle actin), and proliferation markers (Ki
      67 and cyclinD1) were detected by immunohistochemistry assays. Flow cytometry was
      used to evaluate the effect of transforming growth factor beta1 on the CD44+/CD24
      cancer stem cell population. Quantitative real-time polymerase chain reaction
      was employed to assess the gene expression of the stem cell self-renewal markers
      nanog, pou5f1 (coding for Oct4), and sox2. RESULTS: Transforming growth factor
      beta1 increased the formation of liver metastases by the MDA-MB231 (MDA) breast
      cancer cell line but did not affect the liver metastasis of CD44+/CD24+ noncancer
      stem cells. Transforming growth factor beta1 treatment did not significantly
      affect tumor proliferation in vitro or in vivo. Transforming growth factor beta1
      promoted mammary tumor local invasion. Furthermore, the CD44high/CD24- cancer
      stem cell population was also significantly increased by transforming growth
      factor beta1 treatment. Besides, the gene expression of the stem cell self
      renewal markers (nanog, pou5f1, and sox2) and another stem cell surface marker
      (EpCAM) was increased by transforming growth factor beta1 treatment. Finally,
      clusters of CD44-positive breast cancer cells were observed in the livers of mice
      from the control and transforming growth factor beta1 pretreatment groups.
      CONCLUSION: Our results indicate that transforming growth factor beta1 increases
      the local invasive capacity and liver metastasis of breast cancer cells by
      inducing the CD44high/CD24- cancer stem cell population.

PMID- 29658392
TI  - Reconstruction of a Deformed Tumor Based on Fiducial Marker Registration: A
      Computational Feasibility Study.
AB  - Interstitial photodynamic therapy has shown promising results in the treatment of
      locally advanced head and neck cancer. In this therapy, systemic administration
      of a light-sensitive drug is followed by insertion of multiple laser fibers to
      illuminate the tumor and its margins. Image-based pretreatment planning is
      employed in order to deliver a sufficient light dose to the complex locally
      advanced head-and-neck cancer anatomy, in order to meet clinical requirements.
      Unfortunately, the tumor may deform between pretreatment imaging for the purpose
      of planning and intraoperative imaging when the plan is executed. Tumor
      deformation may result from the mechanical forces applied by the light fibers and
      variation of the patient's posture. Pretreatment planning is frequently done with
      the assistance of computed tomography or magnetic resonance imaging in an
      outpatient suite, while treatment monitoring and control typically uses
      ultrasound imaging due to considerations of costs and availability in the
      operation room. This article presents a computational method designed to bridge
      the gap between the 2 imaging events by taking a tumor geometry, reconstructed
      during preplanning, and by following the displacement of fiducial markers, which
      are initially placed during the preplanning procedure. The deformed tumor shape
      is predicted by solving an inverse problem, seeking for the forces that would
      have resulted in the corresponding fiducial marker displacements. The
      computational method is studied on spheres of variable sizes and demonstrated on
      computed tomography reconstructed locally advanced head and neck cancer model.
      Results of this study demonstrate an average error of less than 1 mm in
      predicting the deformed tumor shape, where 1 mm is typically the order of
      uncertainty in distance measurements using magnetic resonance imaging or computed
      tomography imaging and high-quality ultrasound imaging. This study further
      demonstrates that the deformed shape can be calculated in a few seconds, making
      the proposed method clinically relevant.

PMID- 29658395
TI  - Delaying initiation of electroconvulsive treatment after administration of the
      anaesthetic agent and muscle relaxant reduces the necessity of re-stimulation.
AB  - OBJECTIVES: To investigate the effect of delaying initiation of electroconvulsive
      therapy (ECT) after administration of anaesthetic agent and muscle relaxant.
      METHODS: A retrospective cohort study utilizing a case-based analysis comparing
      number of re-stimulations, length of seizures, number of ECTs per series and
      stimulation dosage before and after introducing a new treatment regimen. In 2013,
      ECT was initiated approximately 60-90 seconds after administration of thiopental
      and succinylcholine. This interval was increased to 120 seconds in 2014. Ninety
      three patients were included (40 in 2013 and 53 in 2014). Outcome measures were
      length of seizure, number of re-stimulations, number of ECTs per series and
      stimulation dosage. Regression model analyses were conducted with entering year
      of treatment (2013 vs. 2014), sex and age as covariates. RESULTS: We showed that
      a lowered frequency of re-stimulation was independently associated with the 2014
      treatment regimen. No effect of treatment regimen on duration of seizures as
      measured clinically or by EEG, on number of treatments per series or on
      stimulation dosage was observed. CONCLUSIONS: We found an association between an
      increased time interval from administration of thiopental and succinylcholine to
      ECT and a lowered risk of re-stimulations. The current study substantially
      strengthens the evidence on the benefits of delaying ECT after administration of
      anaesthetic agent and muscle relaxant.

PMID- 29658394
TI  - Management of staghorn renal stones.
AB  - Staghorn stones are large branching stones that fill part of all of the renal
      pelvis and renal calyces and they can be complete or partial depending on the
      level of occupancy of the collecting system. Although kidney stones are commoner
      in men, staghorn stones are less often reported in men compared to women and they
      are usually unilateral. Due to the significant morbidity and potential mortality
      attributed to staghorn stones, prompt assessment and treatment is mandatory.
      Conversely, conservative treatment has been shown to carry a mortality rate of
      28% in 10-year period and 36% risk of developing significant renal impairment.
      Staghorn stones are, therefore, significant disease entity that should be managed
      aggressively and effectively. Generally, the gold standard treatment for staghorn
      stones is surgical with a view to achieve stone-free collecting system and
      preserve renal function. Percutaneous nephrolithotomy should be the recommended
      first-line treatment for staghorn stones. Other non-surgical options are usually
      considered in combination with surgery or as monotherapy only if patients are
      surgically unfit. The decision for optimal treatment of staghorn stones should be
      individualized according to the circumstances of the patient involved and in
      order to do so, a closer look at the advantages and disadvantages of each option
      is necessary.

PMID- 29658396
TI  - Case Studies of Men's Perceptions of Their Online Sexual Interactions With Young
      People: An Interpretative Phenomenological Analysis.
AB  - The aim of the present study was to gain an understanding of the perspectives of
      men who were convicted of committing a sexual offense that included online sexual
      grooming. It explores their experiences of illegal interactions with young people
      via Internet communication platforms, which progressed to physical meetings.
      Semistructured interviews were conducted with two men and analyzed using
      interpretative phenomenological analysis (IPA), providing in-depth accounts of
      their personal experiences. These are presented in a case study format. Three
      dominant themes emerged from the analysis: (a) fulfilling an unmet need, (b)
      spiraling cycle of use, and (c) confrontation with reality. Narrative tones
      employed by the two men were "being trapped in a lie," analogous to a problem
      narrative through which their Internet use was presented as a poor and/or failed
      coping strategy to deal with life stress. Through a process of habituation, their
      Internet use spiraled out of control. A progression was described in terms of
      time spent on the computer, frequency and intensity of online interactions, and
      the impact this had on the men's personal lives, highlighting the "compulsive"
      nature of such interactions for them. A consideration of individual and
      situational vulnerability factors provides new insight into the progression of
      online sexual behavior and contributes to our understanding thereof.

PMID- 29658393
TI  - Key strategies to improve systems for managing patient complaints within health
      facilities - what can we learn from the existing literature?
AB  - BACKGROUND: Information from patient complaints - a widely accepted measure of
      patient satisfaction with services - can inform improvements in service quality,
      and contribute towards overall health systems performance. While analyses of data
      from patient complaints received much emphasis, there is limited published
      literature on key interventions to improve complaint management systems.
      OBJECTIVES: The objectives are two-fold: first, to synthesise existing evidence
      and provide practical options to inform future policy and practice and, second,
      to identify key outstanding gaps in the existing literature to inform agenda for
      future research. METHODS: We report results of review of the existing literature.
      Peer-reviewed published literature was searched in OVID Medline, OVID Global
      Health and PubMed. In addition, relevant citations from the reviewed articles
      were followed up, and we also report grey literature from the UK and the
      Netherlands. RESULTS: Effective interventions can improve collection of
      complaints (e.g. establishing easy-to-use channels and raising patients'
      awareness of these), analysis of complaint data (e.g. creating structures and
      spaces for analysis and learning from complaints data), and subsequent action
      (e.g. timely feedback to complainants and integrating learning from complaints
      into service quality improvement). No one single measure can be sufficient, and
      any intervention to improve patient complaint management system must include
      different components, which need to be feasible, effective, scalable, and
      sustainable within local context. CONCLUSIONS: Effective interventions to
      strengthen patient complaints systems need to be: comprehensive, integrated
      within existing systems, context-specific and cognizant of the information
      asymmetry and the unequal power relations between the key actors. Four gaps in
      the published literature represent an agenda for future research: limited
      understanding of contexts of effective interventions, absence of system-wide
      approaches, lack of evidence from low- and middle-income countries and absence of
      focused empirical assessments of behaviour of staff who manage patient
      complaints.

PMID- 29658397
TI  - Inflammation-coagulation response and thrombotic effects induced by silica
      nanoparticles in zebrafish embryos.
AB  - Nowadays, nanotechnology environmental health and safety (nanoEHS) is gaining
      attention. We previously found that silica nanoparticles (SiNPs) could induce
      vascular endothelial damage. However, the subsequent toxicologic response to
      SiNPs-induced endothelial damage was still largely unknown. In this study, we
      explored the inflammation-coagulation response and thrombotic effects of SiNPs in
      endothelial cells and zebrafish embryos. For in vitro study, swollen mitochondria
      and autophagosome were observed in ultrastructural analysis. The cytoskeleton
      organization was disrupted by SiNPs in vascular endothelial cells. The release of
      proinflammatory and procoagulant cytokines including IL-6, IL-8, MCP-1, PECAM-1,
      TF and vWF, were markedly elevated in a dose-dependent manner. For in vivo study,
      based on the NOAEL for dosimetry selection, and using two transgenic zebrafish,
      Tg(mpo:GFP) and Tg(fli-1:EGFP), SiNPs-induced neutrophil-mediated inflammation
      and impaired vascular endothelial cells. With the dosage higher than NOAEL, SiNPs
      significantly decreased blood flow and velocity, exhibiting a blood
      hypercoagulable state in zebrafish embryos. The thrombotic effect was assessed by
      o-dianisidine staining, showed that an increasing of erythrocyte aggregation
      occurred in SiNPs-treated zebrafish. Microarray analysis was used to screen the
      possible genes for inflammation-coagulation response to SiNPs in zebrafish, and
      the JAK1/TF signaling pathway was further verified by qRT-PCR and Western blot
      assays. For in-deepth study, il6st was knocked down with specific morpholinos.
      The whole-mount in situ hybridization and qRT-PCR analysis showed that the
      expression jak1 and f3b were attenuated in il6st knockdown groups. In summary,
      our data demonstrated that SiNPs could induce inflammation-coagulation response
      and thrombotic effects via JAK1/TF signaling pathway.

PMID- 29658399
TI  - A Qualitative Study to Assess Barber Perceptions of the Feasibility of the
      Employer as a Health Advisor for Obesity Prevention.
AB  - Obesity has become a serious issue affecting millions of Americans, especially in
      the southern United States. One avenue for addressing obesity is the workplace
      setting. This formative research study examined the feasibility of an obesity
      prevention worksite intervention in the barbershop for African American
      barbershop owners (employers) and barbers (employees). The study proposes an
      intervention where the owner of the barbershop would be trained to educate his
      barbers about obesity prevention. Twenty in-depth interviews were conducted with
      the owners ( n = 5) and barbers ( n = 15) of five barbershops in Statesboro,
      Georgia, to determine the feasibility of the intervention. The results of this
      study indicated that the owners and barbers all felt that the intervention was
      feasible and could be implemented in the barbershop. The owners and barbers felt
      that obesity was an important issue in their community. Additional themes
      identified include program benefits, empowerment of owners and barbers, and
      motivational components to help produce healthy habits. The owners felt
      comfortable educating their barbers about obesity prevention, and the barbers
      were receptive toward the idea of being educated by their employer. In order for
      this intervention to be implemented and effective, it must be tailored to fit
      within the barbershop environment. This intervention addresses known health
      disparities that exist in the African American community and underscores the need
      for additional worksite health promotion programs in medically underserved
      communities.

PMID- 29658400
TI  - Corrigendum.
AB  - Naccashian Z, Hattar-Pollara M, Yu CH (A), et al. Prevalence and predictors of
      diabetes mellitus and hypertension in Armenian Americans in Los Angeles. Diabetes
      Educ. 2018;44(2):130-143. Original doi:10.1177/0145721718759981 The author name
      "Chong (Alex) Ho" was inadvertently published without the last name. The author's
      correct name is "Chong Ho (Alex) Yu."

PMID- 29658398
TI  - Live-cell imaging reveals the dynamics and function of single-telomere TERRA
      molecules in cancer cells.
AB  - Telomeres cap the ends of eukaryotic chromosomes, protecting them from
      degradation and erroneous recombination events which may lead to genome
      instability. Telomeres are transcribed giving rise to telomeric repeat-containing
      RNAs, called TERRA. The TERRA long noncoding RNAs have been proposed to play
      important roles in telomere biology, including heterochromatin formation and
      telomere length homeostasis. While TERRA RNAs are predominantly nuclear and
      localize at telomeres, little is known about the dynamics and function of TERRA
      molecules expressed from individual telomeres. Herein, we developed an assay to
      image endogenous TERRA molecules expressed from a single telomere in living human
      cancer cells. We show that single-telomere TERRA can be detected as TERRA RNA
      single particles which freely diffuse within the nucleus. Furthermore, TERRA
      molecules aggregate forming TERRA clusters. Three-dimensional size distribution
      and single particle tracking analyses revealed distinct sizes and dynamics for
      TERRA RNA single particles and clusters. Simultaneous time lapse confocal imaging
      of TERRA particles and telomeres showed that TERRA clusters transiently co
      localize with telomeres. Finally, we used chemically modified antisense
      oligonucleotides to deplete TERRA molecules expressed from a single telomere.
      Single-telomere TERRA depletion resulted in increased DNA damage at telomeres and
      elsewhere in the genome. These results suggest that single-telomere TERRA
      transcripts participate in the maintenance of genomic integrity in human cancer
      cells.

PMID- 29658401
TI  - Probabilistic risk assessment of gold nanoparticles after intravenous
      administration by integrating in vitro and in vivo toxicity with physiologically
      based pharmacokinetic modeling.
AB  - This study aimed to conduct an integrated and probabilistic risk assessment of
      gold nanoparticles (AuNPs) based on recently published in vitro and in vivo
      toxicity studies coupled to a physiologically based pharmacokinetic (PBPK) model.
      Dose-response relationships were characterized based on cell viability assays in
      various human cell types. A previously well-validated human PBPK model for AuNPs
      was applied to quantify internal concentrations in liver, kidney, skin, and
      venous plasma. By applying a Bayesian-based probabilistic risk assessment
      approach incorporating Monte Carlo simulation, probable human cell death
      fractions were characterized. Additionally, we implemented in vitro to in vivo
      and animal-to-human extrapolation approaches to independently estimate external
      exposure levels of AuNPs that cause minimal toxicity. Our results suggest that
      under the highest dosing level employed in existing animal studies (worst-case
      scenario), AuNPs coated with branched polyethylenimine (BPEI) would likely induce
      ~90-100% cellular death, implying high cytotoxicity compared to <10% cell death
      induced by low-to-medium animal dosing levels, which are commonly used in animal
      studies. The estimated human equivalent doses associated with 5% cell death in
      liver and kidney were around 1 and 3 mg/kg, respectively. Based on points of
      departure reported in animal studies, the human equivalent dose estimates
      associated with gene expression changes and tissue cell apoptosis in liver were
      0.005 and 0.5 mg/kg, respectively. Our analyzes provide insights into safety
      evaluation, risk prediction, and point of departure estimation of AuNP exposure
      for humans and illustrate an approach that could be applied to other NPs when
      sufficient data are available.

PMID- 29658402
TI  - Detoxification process of tolaasins, lipodepsipeptides, by Microbacterium sp. K3
      5.
AB  - Tolaasins are antimicrobial lipodepsipeptides. Here, we report the tolaasins
      detoxifying properties of Microbacterium sp. K3-5 (K3-5). The detoxification of
      tolaasins by K3-5 was performed by hydrolyzation of cyclic structure of tolaasins
      depending on the tolaasin-K3-5 cell interaction. Our data suggest that the cyclic
      structure of tolaasins is critical for its interaction to target cells.

PMID- 29658403
TI  - Endobronchial stenting on VV-ECMO in a 6-month-old girl with right lung agenesis
      and severe stenosis of the left main bronchus.
AB  - INTRODUCTION: Lung agenesis is a rare disorder with a variable, but potentially
      very bad clinical course. It necessitates complex clinical management, especially
      in life-threatening situations. CASE REPORT: We describe a case of a 6-month-old
      girl with right lung agenesis who required venovenous extracorporeal membrane
      oxygenation (VV-ECMO) due to pneumonia complicated by exacerbated previously
      diagnosed left main bronchus stenosis. The stenosis was resolved by endobronchial
      intervention and X-ray-guided stent insertion, which enabled weaning from ECMO
      and was aimed at preventing such a life-threatening respiratory failure in the
      future. Unfortunately, even with the functional stent, the baby died 2 months
      post-procedure due to unresolvable bronchial spasms. DISCUSSION: Despite high
      endobronchial stenting-related mortality in children, in cases where no effective
      pharmacological or surgical alternatives exist, stenting may be safely performed
      during VV-ECMO support and be a viable option to overcome critical respiratory
      failure caused by bronchial stenosis.

PMID- 29658404
TI  - Inhibition of miR-21-5p suppresses high glucose-induced proliferation and
      angiogenesis of human retinal microvascular endothelial cells by the regulation
      of AKT and ERK pathways via maspin.
AB  - The aim of the present study is to investigate the role of miR-21-5p in
      angiogenesis of human retinal microvascular endothelial cells (HRMECs). HRMECs
      were incubated with 5 mM glucose, 30 mM glucose or 30 mM mannitol for 24 h, 48 h
      or 72 h. Then, HRMECs exposed to 30 mM glucose were transfected with miR-21-5p
      inhibitor. We found that high glucose increased the expression of miR-21-5p,
      VEGF, VEGFR2 and cell proliferation activity. Inhibition of miR-21-5p reduced
      high glucose-induced proliferation, migration, tube formation of HRMECs, and
      reversed the decreased expression of maspin as well as the abnormal activation of
      PI3K/AKT and ERK pathways. Down-regulation of maspin by siRNA significantly
      increased the activities of PI3K/AKT and ERK pathways. In conclusion, inhibition
      of miR-21-5p could suppress high glucose-induced proliferation and angiogenesis
      of HRMECs, and these effects may partly dependent on the regulation of PI3K/AKT
      and ERK pathways via its target protein maspin.

PMID- 29658405
TI  - Real-time intracochlear imaging of automated cochlear implant insertions in whole
      decalcified cadaver cochleas using ultrasound.
AB  - OBJECTIVES: This study aimed to determine the feasibility of combining high
      frequency ultrasound imaging, automated insertion, and force sensing to yield
      more information about cochlear implant insertion dynamics. METHODS: An apparatus
      was developed combining these aspects along with software to control implant and
      imaging probe positions. Decalcified unfixed human cochleas were implanted at
      various speeds, insertion sites, and implant models while imaging near the
      implant tip throughout insertion and recording force data from the cochlea
      mounting stage. Ultrasound video data were also captured. RESULTS: The basilar
      membrane (BM) was frequently penetrated by the implant in either the mid-basal or
      lower middle turn. Measurements were also performed of apical BM motion in
      response to upstream implant movement at varying insertion speeds. Increasing
      insertion speed resulted in greater BM displacement. DISCUSSION: Multiple
      insertions per cochlea increase the volume of data per specimen while also
      reducing variability due to differences between cochleas. However, to image
      inside the cochlea with ultrasound, the bone had to be decalcified, which likely
      had a significant effect upon the response of tissue to contact by the implant.
      As calcified bone strongly reflects ultrasound, we also found ultrasound imaging
      to be an excellent method for easily assessing bone decalcification progress.
      CONCLUSION: This technique may be very useful for some studies, although the
      confounding effects of bone decalcification may make results of other studies too
      difficult to generalize. The approach could be adapted to other real-time imaging
      modalities, such as optical coherence tomography.

PMID- 29658406
TI  - Designing a neurofeedback device to quantify attention levels using coffee as a
      reward system.
AB  - PURPOSE: Work performance is closely related to one's attention level. In this
      study, a brain-computer interface (BCI) device suitable for office usage was
      chosen to quantify the individual's attention levels. METHODS: A BCI system was
      adopted to interface brainwave signals to a coffee maker via three ascending
      levels of laser detectors. The preliminary test with this prototype was to
      characterize the attention level through the collected coffee amount. Here, the
      preliminary testing was comparing the correlation between the attention level and
      the participants' cumulative grade point average (CGPA) and scores from the 21
      item depression, anxiety, and stress scale (DASS-21) and the attentional control
      scale (ACS) using ordinal regression. It was assumed that a greater CGPA would
      generate a greater attention level. RESULT: The generated coffee amount from the
      BCI system had a significant positive correlation with the CGPA (p = 0.004), mild
      depression (p = 0.019) and mild and extremely severe anxiety (p = 0.044 and p =
      0.019, respectively) and a negative correlation with the ACS score (p = 0.042).
      CONCLUSION: This simple and cost-effective prototype has the potential to enable
      everyone to know their immediate attention level and predict the possible
      correlation to their mental state.

PMID- 29658407
TI  - C-mix: A high-dimensional mixture model for censored durations, with applications
      to genetic data.
AB  - We introduce a supervised learning mixture model for censored durations (C-mix)
      to simultaneously detect subgroups of patients with different prognosis and order
      them based on their risk. Our method is applicable in a high-dimensional setting,
      i.e. with a large number of biomedical covariates. Indeed, we penalize the
      negative log-likelihood by the Elastic-Net, which leads to a sparse
      parameterization of the model and automatically pinpoints the relevant covariates
      for the survival prediction. Inference is achieved using an efficient Quasi
      Newton Expectation Maximization algorithm, for which we provide convergence
      properties. The statistical performance of the method is examined on an extensive
      Monte Carlo simulation study and finally illustrated on three publicly available
      genetic cancer datasets with high-dimensional covariates. We show that our
      approach outperforms the state-of-the-art survival models in this context, namely
      both the CURE and Cox proportional hazards models penalized by the Elastic-Net,
      in terms of C-index, AUC( t) and survival prediction. Thus, we propose a powerful
      tool for personalized medicine in cancerology.

PMID- 29658408
TI  - The compatibility of concurrent high intensity interval training and resistance
      training for muscular strength and hypertrophy: a systematic review and meta
      analysis.
AB  - The purpose of this systematic review and meta-analysis is to assess the effect
      of concurrent high intensity interval training (HIIT) and resistance training
      (RT) on strength and hypertrophy. Five electronic databases were searched using
      terms related to HIIT, RT, and concurrent training. Effect size (ES), calculated
      as standardised differences in the means, were used to examine the effect of
      concurrent HIIT and RT compared to RT alone on muscle strength and hypertrophy.
      Sub-analyses were performed to assess region-specific strength and hypertrophy,
      HIIT modality (cycling versus running), and inter-modal rest responses. Compared
      to RT alone, concurrent HIIT and RT led to similar changes in muscle hypertrophy
      and upper body strength. Concurrent HIIT and RT resulted in a lower increase in
      lower body strength compared to RT alone (ES = -0.248, p = 0.049). Sub analyses
      showed a trend for lower body strength to be negatively affected by cycling HIIT
      (ES = -0.377, p = 0.074) and not running (ES = -0.176, p = 0.261). Data suggests
      concurrent HIIT and RT does not negatively impact hypertrophy or upper body
      strength, and that any possible negative effect on lower body strength may be
      ameliorated by incorporating running based HIIT and longer inter-modal rest
      periods.

PMID- 29658410
TI  - Should developmental prosopagnosia, developmental body agnosia, and developmental
      object agnosia be considered independent neurodevelopmental conditions?

PMID- 29658409
TI  - The influence of marital intimacy on urinary and sexual symptom experience among
      patients with prostate cancer: a cross-sectional study.
AB  - BACKGROUND: Little is known about the influence of how patients with prostate
      cancer perceive emotional support from their spouses on their treatment-related
      symptoms. AIMS: To explore the influence of marital intimacy on urinary and
      sexual symptoms. METHODS: The research participants were 42 men diagnosed with
      prostate cancer recruited from a convenience sample from a university hospital in
      South Korea. The Expanded Prostate Cancer Index Composite, the Korean Marital
      Intimacy Scale, and the Hospital Anxiety and Depression Scale were used to
      measure variables of interest. RESULTS: In the hierarchical multiple regression
      analysis, higher marital intimacy was associated with more favorable symptom in
      the urinary domain. In the sexual domain, none of the models were significant,
      and no influence was found for marital intimacy. CONCLUSIONS: Marital intimacy,
      measured as perceived emotional support from spouses, was found to positively
      influence only the experience of urinary symptoms among South Korean men with
      prostate cancer.

PMID- 29658411
TI  - A possible neuronal account for the behavioural heterogeneity in congenital
      prosopagnosia.

PMID- 29658412
TI  - On defining and interpreting dissociations.

PMID- 29658413
TI  - Objects and faces, faces and objects ....

PMID- 29658414
TI  - Over time, the right results will emerge.
AB  - Scientific research involves going beyond the well-trodden and well-tested ideas
      and theories that form the core of scientific knowledge. During the time
      scientists are working things out, some results will be right, and others will be
      wrong. Over time, the right results will emerge. Lisa Randall (Frank B. Baird,
      Jr. Professor of Science, Physics Department, Harvard University) We are grateful
      to all the commentators for the important and thoughtful comments raised in
      response to the Geskin and Behrmann (G & B) literature survey. The issues raised
      in the introduction to this Special Issue and in these commentaries not only
      address and challenge aspects of the G & B literature review, but contribute
      perspectives and extensions that go well beyond the scope of the review. As is
      evident from G & B and from the 13 commentaries, many aspects of congenital
      prosopagnosia (CP) remain controversial. Adopting the language of the quote
      above, the intention of the G & B survey, along with the commentaries and this
      response, is to establish a collaborative process from which the right results
      (and right theory) will emerge in time. We are grateful to the editor of this
      Special Issue, Dr. Brad Mahon, for his support and for facilitating this
      collaborative exchange in Cognitive Neuropsychology.

PMID- 29658415
TI  - What do associations and dissociations between face and object recognition
      abilities tell us about the domain-generality of face processing?

PMID- 29658416
TI  - On the use of cognitive neuropsychological methods in developmental disorders.

PMID- 29658417
TI  - The face specificity of lifelong prosopagnosia.

PMID- 29658418
TI  - Association vs dissociation and setting appropriate criteria for object agnosia.

PMID- 29658419
TI  - Decoupling category level and perceptual similarity in congenital prosopagnosia.

PMID- 29658420
TI  - Face specificity of developmental prosopagnosia, moving beyond the debate on face
      specificity.

PMID- 29658421
TI  - The power of how-lessons learned from neuropsychology and face processing.

PMID- 29658423
TI  - Prosopdysgnosia? What could it tell us about the neural organization of face and
      object recognition?

PMID- 29658422
TI  - Congenital prosopagnosia: Deficit diagnosis and beyond.

PMID- 29658424
TI  - Commonly associated face and object recognition impairments have implications for
      the cognitive architecture.

PMID- 29658425
TI  - Work and Female Breast Cancer: The State of the Evidence, 2002-2017.
AB  - The authors undertook a scoping review to assess the literature from 2002 to 2017
      on the relationship between occupation and female breast cancer. Case-control,
      cohort, and meta-analytic studies suggest that women working as flight
      attendants, in medical professions, some production positions, sales and retail,
      and scientific technical staff are likely to have elevated risk of breast cancer.
      In addition, occupational exposures to night-shift work, ionizing radiation, some
      chemicals, job stress, and sedentary work may increase risk of breast cancer.
      Occupational physical activity appears to decrease risk. Workplace exposures to
      passive smoke and occupational exposure to nonionizing radiation do not appear to
      affect breast cancer risk. Some studies of occupational categories and workplace
      exposures indicate that risk may be modified by duration of exposure, timing of
      exposure, dose, hormone-receptor subtypes, and menopausal status at diagnosis.
      The compelling data from this review reveal a substantial need for further
      research on occupation and breast cancer.

PMID- 29658427
TI  - Acknowledgments to Translators of State of the Evidence Review articles.

PMID- 29658426
TI  - Work and Breast Cancer: Recommendations to Address Research Needs.
AB  - A review of case-control, cohort, and meta-analytic studies on breast cancer,
      occupation, and work-related exposures from 2002 to 2017 revealed significant
      methodological limitations in the current literature. As part of our review, we
      tabulated the demographic and life history data, breast cancer risk factors,
      occupational history, and exposure estimates collected and analyzed in each
      study. Opportunities exist for future research to explore occupation and breast
      cancer more rigorously and with greater nuance by gathering specific data on age
      at diagnosis, menopausal status, tumor characteristics, demographics, breast
      cancer risk factors, and occupational histories, work roles and settings, and
      exposures. Inclusion of workers in the planning and implementation of research on
      their occupational risks and exposures is one effective way to refine research
      questions and ensure research is relevant to workers' needs and concerns.

PMID- 29658428
TI  - Caregivers' Perspectives of Quality of Life of People With Young- and Late-Onset
      Alzheimer Disease.
AB  - BACKGROUND: Quality of life (QoL) is a growing area of interest in dementia
      research. This study aims to investigate the caregivers' perspective about the
      QoL of people with young-onset Alzheimer disease (YOAD) and late-onset Alzheimer
      disease (LOAD). We also aim to investigate factors that might be associated to
      caregivers' perspective in YOAD and LOAD. METHODS: We included 110 people with
      Alzheimer disease (PwAD; 53 YOAD) and their primary caregivers. The PwAD
      completed assessments about their QoL and cognition. The caregivers provided
      information about the PwAD (demographics, QoL, ability to perform activities of
      daily living, mood, and dementia severity) and had burden of care assessed.
      RESULTS: We did not find a difference in caregivers' perspectives of PwAD QoL
      according to the age at onset. However, the linear regression analysis indicated
      that caregivers' burden ( P < .01) and PwAD depressive symptoms ( P < .05) were
      significantly related to the caregivers' perspective of YOAD QoL. Caregivers'
      burden ( P < .01), years of education ( P < .05), and self-reported QoL ( P <
      .01) were significantly related to the caregivers' perspective of LOAD QoL.
      CONCLUSIONS: The factors that drive the perceptions of caregivers of PwAD QoL may
      vary according to the age at onset. The study provides basic information on
      caregivers' perspectives of PwAD QoL to create more effective interventions
      according to the age at onset.

PMID- 29658429
TI  - Color Vision Impairment Differentiates Alzheimer Dementia From Dementia With Lewy
      Bodies.
AB  - OBJECTIVE: Dementia with Lewy bodies (DLB) is frequently misdiagnosed for
      Alzheimer dementia (AD), especially in its earlier stages. We characterized color
      vision impairment (CVI) in patients with DLB versus patients with AD to determine
      its usefulness in improving accuracy of early diagnosis. METHODS: We
      retrospectively reviewed charts of patients with AD, DLB, and patients with mild
      cognitive impairment suspected to be in the prodromal phase of DLB (pro-DLB) or
      prodromal phase of AD (pro-AD). All patients underwent an online 15-hue color
      vision arrangement test. RESULTS: Fifty-two patients were included in this study
      with a median age of 77 years, of which 44% were female. No significant
      differences in gender, age, or Montreal Cognitive Assessment existed among
      patients with AD (n = 15), pro-AD (n = 5), pro-DLB (n = 8), and DLB (n = 24). Of
      the 52 patients, 4 (2 AD, 1 DLB, and 1 pro-AD) had CVI history from a young age
      and were excluded from final analyses. New-onset CVI prevalence differed
      significantly based on diagnosis: patients with pro-AD (20%), patients with AD
      (15%), patients with pro-DLB (38%), and patients with DLB (78%, P < .001). In a
      stepwise multivariate logistic regression analysis to determine factors
      associated with CVI, "diagnosis type" as a binary variable (DLB or pro-DLB vs AD
      or pro-AD) was the only variable retained in the model (odds ratio = 9.8 [95% CI:
      2.3-42.1], P < .001). CONCLUSIONS: Color vision impairment in patients with DLB
      showed a prevalence similar to the core features of DLB (~80%) and can be
      supportive to a diagnosis of DLB versus AD. Pending prospective confirmation of
      our findings, simple online color vision testing could be incorporated into
      multivariate diagnostic tools to possibly improve accuracy of early diagnosis of
      DLB.

PMID- 29658431
TI  - In silico identification and screening of CYP24A1 inhibitors: 3D QSAR
      pharmacophore mapping and molecular dynamics analysis.
AB  - Vitamin D is a key signalling molecule that plays a vital role in the regulation
      of calcium phosphate homeostasis and bone remodelling. The circulating
      biologically active form of vitamin D is regulated by the catabolic mechanism of
      cytochrome P450 24-hydroxylase (CYP24A1) enzyme. The over-expression of CYP24A1
      negatively regulates the vitamin D level, which is the causative agent of chronic
      kidney disease, osteoporosis and several types of cancers. In this study, we
      found three potential lead molecules adverse to CYP24A1 through structure-based,
      atom-based pharmacophore and e-pharmacophore-based screening methods. Analysis
      was done by bioinformatics methods and tools like binding affinity (binding free
      energy), chemical reactivity (DFT studies) and molecular dynamics simulation
      (protein-ligand stability). Combined computational investigation showed that the
      compounds NCI_95001, NCI_382818 and UNPD_141613 may have inhibitory effects
      against the CYP24A1 protein.

PMID- 29658430
TI  - Adjuvant Pembrolizumab versus Placebo in Resected Stage III Melanoma.
AB  - BACKGROUND: The programmed death 1 (PD-1) inhibitor pembrolizumab has been found
      to prolong progression-free and overall survival among patients with advanced
      melanoma. We conducted a phase 3 double-blind trial to evaluate pembrolizumab as
      adjuvant therapy in patients with resected, high-risk stage III melanoma.
      METHODS: Patients with completely resected stage III melanoma were randomly
      assigned (with stratification according to cancer stage and geographic region) to
      receive 200 mg of pembrolizumab (514 patients) or placebo (505 patients)
      intravenously every 3 weeks for a total of 18 doses (approximately 1 year) or
      until disease recurrence or unacceptable toxic effects occurred. Recurrence-free
      survival in the overall intention-to-treat population and in the subgroup of
      patients with cancer that was positive for the PD-1 ligand (PD-L1) were the
      primary end points. Safety was also evaluated. RESULTS: At a median follow-up of
      15 months, pembrolizumab was associated with significantly longer recurrence-free
      survival than placebo in the overall intention-to-treat population (1-year rate
      of recurrence-free survival, 75.4% [95% confidence interval {CI}, 71.3 to 78.9]
      vs. 61.0% [95% CI, 56.5 to 65.1]; hazard ratio for recurrence or death, 0.57;
      98.4% CI, 0.43 to 0.74; P<0.001) and in the subgroup of 853 patients with PD-L1
      positive tumors (1-year rate of recurrence-free survival, 77.1% [95% CI, 72.7 to
      80.9] in the pembrolizumab group and 62.6% [95% CI, 57.7 to 67.0] in the placebo
      group; hazard ratio, 0.54; 95% CI, 0.42 to 0.69; P<0.001). Adverse events of
      grades 3 to 5 that were related to the trial regimen were reported in 14.7% of
      the patients in the pembrolizumab group and in 3.4% of patients in the placebo
      group. There was one treatment-related death due to myositis in the pembrolizumab
      group. CONCLUSIONS: As adjuvant therapy for high-risk stage III melanoma, 200 mg
      of pembrolizumab administered every 3 weeks for up to 1 year resulted in
      significantly longer recurrence-free survival than placebo, with no new toxic
      effects identified. (Funded by Merck; ClinicalTrials.gov number, NCT02362594 ;
      EudraCT number, 2014-004944-37 .).

PMID- 29658433
TI  - Feasibility of Transabdominal Electrohysterography for Analysis of Uterine
      Activity in Nonpregnant Women.
AB  - PURPOSE: Uterine activity plays a key role in reproduction, and altered patterns
      of uterine contractility have been associated with important physiopathological
      conditions, such as subfertility, dysmenorrhea, and endometriosis. However, there
      is currently no method to objectively quantify uterine contractility outside
      pregnancy without interfering with the spontaneous contraction pattern.
      Transabdominal electrohysterography has great potential as a clinical tool to
      characterize noninvasively uterine activity, but results of this technique in
      nonpregnant women are poorly documented. The purpose of this study is to
      investigate the feasibility of transabdominal electrohysterography in nonpregnant
      women. METHODS: Longitudinal measurements were performed on 22 healthy women in 4
      representative phases of the menstrual cycle. Twelve electrohysterogram-based
      indicators previously validated in pregnancy have been estimated and compared in
      the 4 phases of the cycle. Using the Tukey honest significance test, significant
      differences were defined for P values below .05. RESULTS: Half of the selected
      electrohysterogram-based indicators showed significant differences between menses
      and at least 1 of the other 3 phases, that is the luteal phase. CONCLUSION: Our
      results suggest transabdominal electrohysterography to be feasible for analysis
      of uterine activity in nonpregnant women. Due to the lack of a golden standard,
      this feasibility study is indirectly validated based on physiological
      observations. However, these promising results motivate further research aiming
      at evaluating electrohysterography as a method to improve understanding and
      management of dysfunctions (possibly) related to altered uterine contractility,
      such as infertility, endometriosis, and dysmenorrhea.

PMID- 29658432
TI  - Novel assay system for acidic Peptide:N-glycanase (aPNGase) activity in crude
      plant extract.
AB  - Acidic peptide:N-glycanase (aPNGase) plays a pivotal role in plant glycoprotein
      turnover. For the construction of aPNGase-knockout or -overexpressing plants, a
      new method to detect the activity in crude plant extracts is required because
      endogenous peptidases present in the extract hamper enzyme assays using
      fluorescence-labeled N-glycopeptides as a substrate. In this study, we developed
      a new method for measuring aPNGase activity in crude extracts from plant
      materials.

PMID- 29658434
TI  - Bone Marrow-Derived Cells Trafficking to the Oviduct: Effect of Ischemia
      Reperfusion Injury.
AB  - The oviduct/fallopian tube is a crucial organ in the mammalian reproductive
      tract; it plays a critical role in gamete transportation and early embryo
      development. In women, torsion of the fallopian tubes can cause ischemia and
      reperfusion (IR) injury. In this study, we tested the effect of this injury on
      recruitment of bone marrow-derived cells (BMDCs) to the oviducts of reproductive
      age female mice. Bone marrow-derived cells were collected from ubiquitin-green
      fluorescent protein-positive male mice and transplanted into wild-type female
      mice. Ischemia and reperfusion injury was performed in half of the mice, while
      controls received equivalent surgery without oviduct injury. Two weeks following
      injury, recruitment of BMDCs to the oviducts was analyzed in both groups.
      Ischemia and reperfusion injury caused a greater than 2-fold increase in BMDC
      recruitment to the injured oviducts compared to those without injury.
      Specifically, the recruitment of BMDCs was localized to the stroma of the
      oviduct. We demonstrate that IR injury to oviduct recruits BMDCs to this tissue
      and suggest that BMDCs have function in the healing process.

PMID- 29658435
TI  - Combined Immunotherapy (OK-432, IL-2) With Chemotherapy Decrease the Recurrence
      Rate in Advanced Ovarian Cancer.
AB  - OBJECTIVE: In advanced ovarian cancer, traditional therapy included debulking
      surgery and postoperative chemotherapy. We proposed immunochemotherapy (IMCT)
      combined with picibanil (OK-432), interleukin-2 (IL-2), and traditional platinum-
      and taxol-based chemotherapy as a better treatment option for advanced ovarian
      cancer. METHODS: We retrospectively reviewed the medical records of 51 patients
      with advanced ovarian cancer between 2007 and 2015 at Chang Gung Memorial
      Hospital Linkou Medical Center, including 26 patients who were treated with OK
      432, IL-2, and platinum- and taxol-based chemotherapy (IMCT group) after
      debulking surgery; another 25 were treated with traditional platinum- and taxol
      based chemotherapy (traditional chemotherapy group) after debulking surgery. We
      analyzed the difference in age, follow-up period, recurrence rate, and diagnosis
      to-recurrence period between the 2 groups. We also analyzed the difference in
      complete blood cell counts, differentiating counts, and cancer antigen 125 (CA
      125) at 1 month after treatment. RESULTS: The recurrence rate between the IMCT
      and traditional chemotherapy groups showed a significant difference (53.8% vs
      88%; P = .0128). The diagnosis-to-recurrence duration was longer in the IMCT than
      in the traditional chemotherapy groups (33.21 vs 25.63 months), although no
      statistical significance was found ( P = .4668). In laboratory analysis at 1
      month after treatment, the white blood cell, absolute neutrophil, and absolute
      lymphocyte counts (ALCs) were significantly higher in the IMCT group. On the
      other hand, CA-125 was significantly lower, and ALC was significantly higher in
      the nonrecurrence group. CONCLUSIONS: Combined IMCT and chemotherapy have lower
      recurrence rate compared to traditional chemotherapy after debulking surgery for
      the treatment of advanced ovarian cancer.

PMID- 29658436
TI  - Thrombin Alters Human Endometrial Stromal Cell Differentiation During
      Decidualization.
AB  - Vaginal bleeding and subchorionic hematomas are associated with increased risk of
      both early and late pregnancy loss. Thrombin generation may play a pivotal role
      in the development of these complications. To determine the effects of thrombin
      on human endometrial stromal cells (hESCs), cells were treated with thrombin at
      baseline or during decidualization with cyclic adenosine monophosphate
      (cAMP)+medroxyprogesterone acetate (MPA). Next-generation RNA sequencing revealed
      that markers of decidualization (IGF-1, IGFBP-1, and prolactin [PRL]) were
      induced after the initiation of decidualization, whereas thrombin suppressed
      insulin-like growth factor ( IGF)-1, Insulin-like growth factor binding protein (
      IGFBP)-1, and PRL gene expression at baseline and during decidualization. These
      effects were mediated through protease activated receptor (PAR)-1- and PAR-1
      independent pathways. Thrombin decreased the secretion of a key marker of
      decidualization (PRL), altered the morphological transformation of decidualizing
      hESCs, and activated genes involved in matrix degradation and proinflammatory
      chemokines ( Interleukin-8 and Interleukin-6). Genes encoding factors important
      for matrix stability ( Col1alpha1, LOX) were suppressed. We suggest that
      intrauterine bleeding and generation of thrombin accentuates leukocyte
      extravasation and endometrial inflammation, impairs decidualization, and
      endometrial support of early pregnancy.

PMID- 29658437
TI  - Decreased Expression of HOXA10 May Activate the Autophagic Process in Ovarian
      Endometriosis.
AB  - Autophagy is a survival process that maintains homeostasis in all eukaryotic
      cells. Recent studies show an abnormal autophagic activity in endometriosis, but
      the role of autophagy is controversial. Homeobox A10 (HOXA10) is a transcription
      factor necessary for embryonic and adult uterine development, and studies
      indicate that its expression decreases in endometriosis. Homeobox A10 may
      negatively regulate autophagy in endometriosis. To test this hypothesis, we
      measured the expression levels of autophagic biomarkers (beclin-1 and LC3-II) and
      HOXA10 proteins by Western blotting and messenger RNA (mRNA) by quantitative real
      time polymerase chain reaction. Furthermore, we evaluated the serum cancer
      antigen 125 (CA125) levels by immunoassay. Most tested autophagic biomarker
      proteins and mRNAs were upregulated, whereas HOXA10 protein and mRNA were
      decreased in ovarian endometriomas compared with eutopic endometria of women with
      endometriosis and normal endometria. Compared with normal endometrium, only
      protein expression levels of autophagic biomarkers were increased in the eutopic
      endometrium of women with endometriosis. Moreover, HOXA10 was found to have a
      significant negative correlation with autophagy ( P < .01). Serum CA125 was at a
      high level in endometriosis and increased with elevated revised American
      Fertility Society staging (I-IV). There was a significant positive correlation
      between serum CA125 level and LC3-II protein level and/or LC3-II/LC3-I ratio ( P
      < .01) and a significant negative correlation between serum CA125 level and
      HOXA10 gene level ( P < .01). In conclusion, our studies support that the
      deficiency of HOXA10 may induce autophagy in endometriosis, and the relationship
      among CA125, autophagy, and HOXA10 in endometriosis requires additional research.

PMID- 29658438
TI  - A Systematic Review of First Trimester Biochemical and Molecular Predictive Tests
      for Preeclampsia.
AB  - BACKGROUND: Preeclampsia is a multisystem disorder affecting 5%-8% of pregnant
      women. Considering the ongoing debate over the predicting value of some
      commercial first trimester tests, the aim of this study was to compare the
      existing first-trimester screening tests for preeclampsia. METHODS: In this
      systematic review, relevant articles published during 2000-2017 were extracted
      from PubMed, Science Direct, Scopus, Cochrane Library, ISI Web of Science, and
      ProQuest databases. After a thorough evaluation of the 412 potentially eligible
      papers, only 28 papers were selected based on the inclusion criteria. RESULTS:
      From a total of 412 retrieved studies, 28 papers were found eligible. Most
      studies had casecontrol or nested case-control designs. A total of 15164 pregnant
      women were evaluated in the reviewed studies. Various tests were applied in the
      first trimester of pregnancy to predict the development of preeclampsia. The most
      commonly used biomarkers were uterine artery pulsatility index, pregnancy
      associated plasma protein A (PAPP-A), adiponectin, human chorionic gonadotropin
      (hCG) hormone and inhibin-A. Other tests were used in only one or two studies.
      CONCLUSION: Based on this review, a combination of markers should be evaluated
      for the identification of high-risk women. Novel methods measuring multiple
      markers will hopefully facilitate the development of clinically effective
      screening programs in the future.

PMID- 29658439
TI  - Hypertension and Aortic Stenosis: A Review.
AB  - BACKGROUND: Aortic stenosis is a common form of valvular heart disease which
      often coexists with hypertension. These diseases represent two distinct forms of
      left ventricular systolic overload and in combination may be associated with
      disadvantageous left ventricular remodeling, increased mortality and heart
      failure. The treatment of hypertension in aortic stenosis remains a challenging
      problem with limited data to guide clinical practice. METHODS: We performed a
      comprehensive online literature review to find relevant published literature on
      the topic of hypertension and aortic stenosis. RESULTS: In the present
      manuscript, we review the pathophysiology of aortic stenosis in combination with
      hypertension and the effects on the left ventricle. We also provide general
      recommendations for medical therapy for treatment of hypertension in aortic
      stenosis and review the available data on specific antihypertensive agents in
      this context. CONCLUSIONS: Aortic stenosis and hypertension commonly coexist and
      significantly impact the diagnosis and classification of aortic stenosis severity
      and symptoms. Treatment of hypertension among patients with severe aortic
      stenosis can be challenging. Among specific antihypertensive agents studied in
      this context, ACE-inhibitors are the most well studied.

PMID- 29658440
TI  - Effects of Transcutaneous Electrical Nerve Stimulation in Autonomic Nervous
      System of Hypertensive Patients: A Randomized Controlled Trial.
AB  - BACKGROUND: Patients with hypertension have altered autonomic nervous system
      function, which are increased sympathetic activity. Transcutaneous Electrical
      Nerve Stimulation (TENS) is a useful modality for pain control and has also been
      shown to be effective in the reduction of sympathetic activity in healthy
      subjects and individuals with cardiovascular diseases. OBJECTIVE: The aim of this
      study was to verify the effects of transcutaneous electrical nerve stimulation by
      the evaluation of heart rate variability (HRV) in patients with essential
      hypertension. METHOD: Twenty-eight patients received an application of low
      frequency TENS(4 Hz) n=8, highfrequency TENS (100 Hz) n=10 or placebo TENS n=10
      in paravertebral ganglionar region during thirty minutes. RESULTS: After 4 Hz
      TENS, there was a decrease in the low-frequency (LFn.u.) component (57.71+/-9.46
      vs 45.58+/-13.51, p<0.026) and an increase in the high-frequency (HFn.u.)
      component (33.03+/-13.83 vs 45.83+/-20.19, p <0.05) of HRV. After 100 Hz TENS and
      placebo, there were no changes in the LF and HF components. No significant
      differences were found in systolic blood pressure with low-frequency TENS
      (129.37+/- 15.48 vs 126.69 +/- 15.21, p<0.490). There was an increase, although
      not significant, with high-frequency TENS (131.00 +/- 15.97 vs 138.75 +/- 25.79,
      p<0.121) and placebo (133.80 +/- 29.85 vs 134.80 +/- 29.72, p< 0.800). No
      differences were found in the diastolic blood pressure with low-frequency TENS
      and placebo, but there was a significant increase in high-frequency TENS (81.00
      +/- 11.78 vs 85.65 +/- 13.68, p< 0.018). CONCLUSION: Low-frequency TENS decreases
      sympathetic nervous system activity and increases parasympathetic nervous system
      activity and high-frequency TENS increases diastolic blood pressure, when applied
      on the paravertebral ganglionar region in the hypertensive patients.

PMID- 29658441
TI  - Efficacy of Transcranial Direct Current Stimulation Combined with Cognitive
      Training in the Treatment of Apathy in Patients with Alzheimer's Disease: Study
      Protocol for a Randomized Trial.
AB  - BACKGROUND: Apathy, commonly defined as the loss of motivation, is a symptom
      frequently encountered in Alzheimer's Disease (AD). The treatment of apathy
      remains challenging in the absence of any truly effective medications.
      Transcranial Magnetic Stimulation (rTMS) or Transcranial Direct Current
      Stimulation (tDCS) can improve cognitive disorders, but do not appear to improve
      apathy. Isolated cognitive training also appears to have no effect on apathy. We
      propose to test the efficacy of a new procedure for the treatment of apathy in AD
      patients consisting of a combination of tDCS and cognitive training, based on the
      latest guidelines for the design of therapeutic trials in this field.
      METHODS/DESIGN: This article primarily describes the design of a monocentre,
      randomized, doubleblind trial to be conducted in France to evaluate the effect of
      the combination of tDCS and cognitive training on apathy compared to a group
      treated exclusively by cognitive training (sham tDCS). Twenty- four patients
      under the age of 90 years with mild-to-moderate Alzheimer's disease (Mini Mental
      State Examination score between 15 and 26/30) (MMSE)) presenting clinically
      significant apathy evaluated by the Apathy Inventory (AI) and the
      NeuroPsychiatric Inventory (NPI) apathy subscore will be enrolled. Severe
      depression will be excluded by using the NPI depression subscore. Treatment will
      comprise 10 sessions (D0-D11) including tDCS (bilateral prefrontal, temporal and
      parietal targets) and Cognitive Training (Cog) (6 simple tasks involving working
      memory, language and visuospatial function). After randomization (ratio 2:1), 16
      patients will receive the complete treatment comprising tDCS and Cog (group 1)
      and 8 patients will be treated exclusively by Cog (sham tDCS) (group 2). The
      primary endpoint will be a significant improvement of the AI score by comparing
      baseline measures (D-15) to those recorded one month after stopping treatment
      (D44). Secondary endpoints will be an improvement of this score immediately after
      treatment (D14), 2 weeks (D29) and 2 months (D74) after stopping treatment and
      improvement of the MMSE score, NPI apathy subscore, ADAS Cog (Alzheimer Disease
      Assessment cognitive Scale subsection), ADCS-ADL (Alzheimer Disease Cooperative
      Study-Activities of Daily Living), FAB (Frontal Assessment Battery) and the
      latency of P300 evoked potentials at the same timepoints. CONCLUSION: The purpose
      of our study is to check the assumption of tDCS and cognitive training efficacy
      in the treatment of apathy encountered in AD patients and we will discuss its
      effect over time.

PMID- 29658442
TI  - Evaluation of In Silico Anti-parkinson Potential of beta-asarone.
AB  - INTRODUCTION: Parkinson's disease is affecting millions of people worldwide. The
      prevalence of Parkinson's disease is 0.3% globally, rising to 1% in more than 60
      years of age and 4% in more than 80 years of age and the figures are thought to
      be doubled by 2030. Thus, there is a great need to identify novel therapeutic
      strategies or candidate drug molecule which can rescue neuronal degeneration.
      beta -asarone has the potential to act as a neuroprotective agent but regarding
      its role in Parkinson's disease, very few reports are available. Thus, this study
      was undertaken to unlock the potential of beta-asarone against Parkinson's
      disease. MATERIAL AND METHODS: The Absorption, Distribution, Metabolism, and
      Excretion (ADME) analysis has been done by using Swiss ADME Predictor. The
      interactions of beta-asarone with dopaminergic receptors were investigated by
      Glide Program 5.0. The crystal structures of dopamine receptors were retrieved
      from Research Collaboratory for Structural Bioinformatics- Protein Data Bank
      (RCSB-PDB). The structure of beta-asarone was drawn in Chem Draw Ultra 7.0.1.
      Finally, the toxicity of beta-asarone has been predicted by using online web
      servers like Lazar and Protox. RESULTS AND DISCUSSION: The ADME data of current
      investigation has shown good oral bioavailability of beta-asarone. It also showed
      a good binding affinity towards dopaminergic receptors. Further, it was found to
      be interacting through hydrogen bond with different amino acid residues of D2 and
      D3 receptors. However, beta-asarone was predicted to be toxic in various species
      of rodents, as per the results of toxicity online web servers. CONCLUSION: Based
      on the current finding from ADME and docking studies, these preliminary results
      may act as effective precursor tool for the development of beta-asarone as a
      promising anti-Parkinson agent. However, furthermore experimental validation
      using in-vitro & in-vivo studies is needed to explore their therapeutic andtoxic
      effects.

PMID- 29658443
TI  - Evaluation of the Effect of Uremic Serum on Hepatic Reductase Functional
      Expression.
AB  - BACKGROUND: The nonrenal clearance of drugs mediated by hepatic reduction is
      selectively altered by kidney disease. This study evaluated the influence of
      uremic serum on the expression and activity of reductase enzymes. METHODS: Human
      hepatocellular carcinoma cells (HepG2) were incubated with 5% pooled serum
      collected from patients with hemodialysis (pre- and post-dialysis session) or
      control subjects. The mRNA expression of various aldo-keto (AKR1C) and carbonyl
      (CBR) reductases were measured. Reductase metabolic activity was assessed in
      human liver cytosol or HepG2 cells using naltrexone as a substrate. RESULTS:
      Incubation of cells with pre-dialysis serum resulted in significant upregulation
      of AKR1C4 (by 63.2%) and CBR1 (by 34.6%) versus control serum. This increase was
      not observed for AKR1C1 and CBR1 with serum collected post-dialysis. While uremic
      serum had no effect on reductase activity, some instances with differences in
      metabolite formation among individual's pre- and post-dialysis samples were
      observed. CONCLUSION: Although uremic serum can upregulate mRNA expression of
      several reductases, this effect was not observed at the activity level. Future
      studies are necessary to improve our understanding of the mechanistic effects of
      impaired kidney function on drug reduction.

PMID- 29658444
TI  - Development of 225Ac Radiopharmaceuticals: TRIUMF Perspectives and Experiences.
AB  - BACKGROUND: The development of radiopharmaceuticals containing 225Ac for targeted
      alpha therapy is an active area of academic and commercial research worldwide.
      OBJECTIVES: Despite promising results from recent clinical trials, 225Ac
      radiopharmaceutical development still faces significant challenges that must be
      overcome to realize the widespread clinical use of 225Ac. Some of these
      challenges include the limited availability of the isotope, the challenging
      chemistry required to isolate 225Ac from any co-produced isotopes, and the need
      for stable targeting systems with high radiolabeling yields. RESULTS: Here we
      provide a review of available literature pertaining to these challenges in the
      225Acradiopharmaceutical field and also provide insight into how performed and
      planned efforts at TRIUMF - Canada's particle accelerator centre - aim to address
      these issues.

PMID- 29658446
TI  - Colorectal cancers survivors' adherence to lifestyle recommendations and cross
      sectional associations with health-related quality of life.
AB  - The lifestyle recommendations of the World Cancer Research Fund (WCRF)/American
      Institute for Cancer Research (AICR) are primarily intended for cancer
      prevention. In the absence of specific recommendations for cancer survivors, we
      investigated adherence of colorectal cancer (CRC) survivors to the WCRF/AICR
      lifestyle recommendations and associations with health-related quality of life
      (HRQoL). The cross-sectional part of the Energy for life after ColoRectal cancer
      (EnCoRe) study was conducted in 155 CRC survivors (stage I-III), 2-10 years post
      diagnosis. Dietary intake, physical activity and general body fatness were
      measured by 7-d food diaries, by questionnaires and accelerometers and BMI,
      respectively. Adherence to each of the ten WCRF/AICR recommendations was scored
      as 0 (no/low adherence), 0.5 (moderate adherence) or 1 point (complete
      adherence), and summed into an overall adherence score (range: 0-10). HRQoL,
      disability and distress were assessed by validated questionnaires. Associations
      of the overall WCRF/AICR adherence score with HRQoL outcomes were analysed by
      confounder-adjusted linear regression. The mean adherence score was 5.1 (sd 1.4,
      range: 1.5-8.5). In confounder-adjusted models, a higher adherence score was
      significantly associated with the HRQoL dimension better physical functioning
      (beta per 1 point difference in score: 2.6; 95 % CI 0.2, 5.1) and with less
      fatigue (beta: -3.3; 95 % CI -6.4, -0.1). In conclusion, higher adherence of CRC
      survivors to WCRF/AICR lifestyle recommendations for cancer prevention was
      associated with better physical functioning and with less fatigue. This study
      adds to the limited knowledge on adherence to lifestyle behaviours in CRC
      survivors and relationships with quality of life. Prospective studies are needed
      to investigate longitudinal associations.

PMID- 29658445
TI  - Improved Detection of Circulating miRNAs in Serum and Plasma Following Rapid
      Heat/Freeze Cycling.
AB  - BACKGROUND: The measurement of circulating miRNAs has proven to be a powerful
      biomarker tool for several disease processes. Current protocols for the detection
      of miRNAs usually involve an RNA extraction step, requiring a substantial volume
      of patient serum or plasma to obtain sufficient input material. OBJECTIVE: Here,
      we describe a novel methodology that allows detection of a large number of miRNAs
      from a small volume of serum or plasma without the need for RNA extraction.
      METHODS: Three MUl of serum or plasma was subjected to three cycles of high and
      low temperatures (heat/freeze cycles) followed by miRNA arrays. RESULTS: Our
      results indicate that miRNA detection following this process is highly
      reproducible when comparing multiple samples from the same subject. Moreover,
      this protocol increases the reproducibility of miRNA detection in samples that
      were previously subjected to multiple freeze-thaw cycles. Importantly, the
      detection of miRNAs from serum vs. plasma following heat/freeze cycling are
      highly comparable, indicating that this heat/freeze process effectively
      eliminates differences in detection between serum and plasma samples that have
      been reported using other sample preparation methodologies. CONCLUSION: We
      propose that this method is a potent alternative to current RNA extraction
      protocols, substantially reducing the amount of sample necessary for miRNA
      detection while simultaneously improving miRNA detection and reproducibility.

PMID- 29658447
TI  - [Treatment and prognosis of pulmonary hemorrhage in preterm infants during 2007
      2016].
AB  - OBJECTIVE: To study the treatment and prognosis of pulmonary hemorrhage in
      preterm infants. METHODS: A total of 106 preterm infants diagnosed with pulmonary
      hemorrhage, who were hospitalized in the neonatal ward of Peking University Third
      Hospital between 2007 and 2016, were enrolled. These patients were divided into
      2007-2011 group (34 cases) and 2012-2016 group (72 cases) according to the time
      of hospitalization, divided into conventional-frequency ventilation group (43
      cases) and high-frequency oscillatory ventilation (HFOV) group (63 cases)
      according to the respiratory support method used after the development of
      pulmonary hemorrhage, and divided into non-operation group (34 cases) and
      operation group (14 cases) according to whether PDA ligation was performed for
      the unclosed PDA before pulmonary hemorrhage. The general data, treatment, and
      prognosis were compared between different groups. RESULTS: Compared with the 2007
      2011 group, the 2012-2016 group had higher rates of HFOV and PDA ligation
      (P<0.05), a lower mortality rate during hospitalization (P<0.05), a longer length
      of hospital stay (P<0.05), and higher incidence rates of intracranial hemorrhage
      and bronchopulmonary dysplasia (P<0.05). Compared with the conventional-frequency
      ventilation group, the HFOV group had a lower mortality rate during
      hospitalization (P<0.05), a longer length of hospital stay (P<0.05), and higher
      incidence rates of intracranial hemorrhage and bronchopulmonary dysplasia
      (P<0.05). Compared with the non-operation group, the operation group had a lower
      mortality rate during hospitalization (P<0.05), a longer length of hospital stay
      (P<0.05), and higher incidence rates of intracranial hemorrhage and
      bronchopulmonary dysplasia (P<0.05). CONCLUSIONS: The application of HFOV and PDA
      ligation can improve the survival rate of preterm infants with pulmonary
      hemorrhage, but the incidence of intracranial hemorrhage and bronchopulmonary
      dysplasia is also increased.

PMID- 29658448
TI  - [Clinical features and prognosis of preterm infants with varying degrees of
      bronchopulmonary dysplasia].
AB  - OBJECTIVE: To study the clinical features and prognosis of preterm infants with
      varying degrees of bronchopulmonary dysplasia (BPD). METHODS: The clinical data
      of 144 preterm infants with a gestational age of <32 weeks who were admitted to
      the neonatal intensive care unit from March 2014 to March 2016 and were diagnosed
      with BPD were collected. According to the severity of BPD, these preterm infants
      were divided into mild group with 81 infants and moderate/severe group with 63
      infants. The two groups were compared in terms of perinatal risk factors,
      treatment, comorbidities, complications, and prognosis of the respiratory system.
      RESULTS: Compared with the mild BPD group, the moderate/severe BPD group had a
      significantly higher gestational age and rate of small-for-gestational-age (SGA)
      infants (P<0.05), as well as a significantly higher rate of severe preeclampsia
      and a significantly lower rate of threatened preterm labor (P<0.05). Compared
      with the mild BPD group, the moderate/severe BPD group had a significantly higher
      percentage of infants who needed mechanical ventilation at 2 weeks after birth,
      longer duration of mechanical ventilation, total time of oxygen therapy, and
      length of hospital stay, and higher incidence rates of pneumonia and cholestasis
      (P<0.05), as well as a significantly lower application rate of caffeine citrate
      (P<0.05). The multivariate logistic regression analysis showed that SGA birth
      (OR=5.974, P<0.05), pneumonia (OR=2.590, P<0.05), and mechanical ventilation
      required at 2 weeks after birth (OR=4.632, P<0.05) were risk factors for
      increased severity of BPD. The pulmonary function test performed at the corrected
      gestational age of 40 weeks showed that compared with the mild BPD group, the
      moderate/severe BPD group had significantly lower ratio of time to peak tidal
      expiratory flow to total expiratory time, ratio of volume to peak tidal
      expiratory flow to total expiratory volume, and tidal expiratory flow at 25%
      remaining expiration (P<0.05). The infants were followed up to the corrected
      gestational age of 1 year, and the moderate/severe BPD group had significantly
      higher incidence rates of recurrent hospital admission for pneumonia and
      recurrent wheezing (P<0.05). CONCLUSIONS: SGA birth, pneumonia, and prolonged
      mechanical ventilation are associated with increased severity of BPD. Infants
      with moderate or severe BPD have poor pulmonary function and may experience
      recurrent infection and wheezing.

PMID- 29658449
TI  - [Intrauterine growth status of twin neonates with a gestational age of 27-40
      weeks].
AB  - OBJECTIVE: To establish the intrauterine growth curve of twin neonates, and to
      investigate the intrauterine growth status of twin neonates. METHODS: Cross
      sectional cluster sampling was performed for an on-the-spot investigation of 1
      296 live twin neonates who were born in two hospitals in Shenzhen between April
      2013 and September 2015. The Lambda-Mu-Sigma method was used for the curve
      fitting of body weight, body length, head circumference, chest circumference, and
      crown-rump length. RESULTS: The means and 3rd-97th percentile intrauterine growth
      curves for body weight, body length, head circumference, chest circumference, and
      crown-rump length were obtained for the 1 296 twin neonates with a gestational
      age of 27-40 weeks. The curve values of the 1 296 twin neonates for body weight,
      body length, head circumference, chest circumference, and crown-rump length were
      all lower than those of singleton neonates in Shenzhen that had been reported,
      and the difference increased with increasing gestational age. CONCLUSIONS: The
      intrauterine growth curves for body weight, body length, head circumference,
      chest circumference, and crown-rump length of twin neonates with a gestational
      age of 27-40 weeks in Shenzhen obtained in this study can provide a reference for
      evaluating the intrauterine growth status of twin neonates among the current
      population in Shenzhen.

PMID- 29658450
TI  - [Influence of acute pancreatitis in pregnancy on pregnancy outcomes and
      neonates].
AB  - OBJECTIVE: To study the influence of acute pancreatitis in pregnancy (APIP) on
      pregnancy outcomes and neonates. METHODS: A retrospective analysis was performed
      for 33 APIP patients and 31 neonates born alive. RESULTS: Of the 33 APIP
      patients, 26 (79%) developed APIP in the late pregnancy. Fourteen (45%) patients
      had hyperlipidemic APIP, 13 (42%) had biliary APIP, and 4 (13%) had other types
      of APIP. According to the severity, 22 (67%) were mild APIP, 5 (15%) were
      moderate APIP, and 6 were severe APIP. None of the 33 APIP patients died. Among
      the 20 patients with term delivery, 11 underwent termination of pregnancy; among
      the 10 patients with preterm delivery, 9 underwent termination of pregnancy; two
      patients experienced intrauterine fetal death, and one experienced abortion
      during the second trimester. Among the 31 neonates born alive (two of them were
      twins), 1 (3%) died, 12 (39%) experienced neonatal hyperbilirubinemia, 8 (26%)
      had neonatal hypoglycemia, 6 (19%) had neonatal respiratory distress syndrome, 5
      (16%) experienced infectious diseases, and 2 (6%) experienced intracranial
      hemorrhage. The hyperlipidemic APIP group had a higher percentage of patients
      undergoing termination of pregnancy than the biliary APIP and other types of APIP
      groups (P<0.05). The incidence rate of preterm infants in the moderate APIP was
      higher than in the mild and severe APIP groups (P<0.05). The mean birth weights
      of neonates were the lowest in the moderate APIP group. The incidence rates of
      neonatal respiratory distress syndrome, intracranial hemorrhage, and infectious
      disease were the lowest in the mild APIP group (P<0.05). CONCLUSIONS: APIP can
      lead to adverse pregnancy outcomes and neonatal diseases, which are associated
      with the severity of pancreatitis.

PMID- 29658451
TI  - [Clinical and genetic analysis of a pediatric patient with sodium taurocholate
      cotransporting polypeptide deficiency].
AB  - Sodium taurocholate cotransporting polypeptide (NTCP) deficiency is an inborn
      error of bile acid metabolism caused by mutations of SLC10A1 gene. This paper
      reports the clinical and genetic features of a patient with this disease. A 3.3
      month-old male infant was referred to the hospital with the complaint of
      jaundiced skin and sclera over 3 months. Physical examination revealed moderate
      jaundice of the skin and sclera. The liver was palpable 3.5 cm below the right
      subcostal margin with a medium texture. Serum biochemistry analysis revealed
      markedly elevated bilirubin (predominantly direct bilirubin) and total bile acids
      (TBA), as well as decreased 25-OH-VitD level. On pathological analysis of the
      biopsied liver tissue, hepatocyte ballooning and cholestatic multinucleate giant
      cells were noted. The lobular architecture was distorted. Infiltration of
      inflammatory cells, predominantly lymphocytes, was seen in the portal tracts. In
      response to the anti-inflammatory and liver protective drugs as well as fat
      soluble vitamins over 2 months, the bilirubin and transaminases levels were
      improved markedly while the TBA kept elevated. Because of persisting
      hypercholanemia on the follow-up, SLC10A1 gene analysis was performed at his age
      of 17.2 months. The child proved to be a homozygote of the reportedly pathogenic
      variant c.800C>T (p. Ser267Phe), while the parents were both carriers. NTCP
      deficiency was thus diagnosed. The infant was followed up until 34.3 months old.
      He developed well in terms of the anthropometric indices and neurobehavioral
      milestones. The jaundice disappeared completely. The liver size, texture and
      function indices all recovered. However, the hypercholanemia persisted, and the
      long-term outcome needs to be observed.

PMID- 29658452
TI  - [Clinical features and gene mutations of primary immunodeficiency disease: an
      analysis of 7 cases].
AB  - This research investigated the clinical features of immunodeficiency disease and
      the features of the mutation of its pathogenic genes. All 7 patients were boys
      aged 5 months to 4 years and 6 months and had a history of recurrent respiratory
      infection and pneumonia, low levels of IgM and IgG, and abnormal absolute values
      or percentages of lymphocyte subsets. High-throughput sequencing showed c.1684C>T
      mutations in the BTK gene in patient 1 and IVS8+2T>C splice site mutations in the
      BTK gene in patient 2. Both of these mutations came from their mothers. Patients
      3, 4, and 5 had mutations in the IL2RG gene, i.e., c.298C>T, IVS3-2A>G, and
      c.164T>A, among which c.164T>A mutations had not been reported. Patient 6 had
      c.204C>G mutations in the RAG2 gene. Patient 7 had complex heterozygous mutations
      of c.913C>T and c.824G>A in the RAG2 gene, which came from his father and mother,
      respectively. Patients with immunodeficiency disease have abnormal immunological
      indices, and high-throughput sequencing helps to make a definite diagnosis.

PMID- 29658453
TI  - [BRAF-V600E mutation and its clinical significance in children with Langerhans
      cell histiocytosis].
AB  - OBJECTIVE: To investigate the clinical significance of BRAF-V600E mutation in
      children with Langerhans cell histiocytosis (LCH). METHODS: Real-time
      fluorescence quantitative PCR was used to detect BRAF-V600E mutation in paraffin
      embedded tissue samples from 26 children with LCH. A retrospective analysis was
      performed for the association of BRAF-V600E mutation with clinical features and
      prognosis of children with LCH. RESULTS: Of the 26 children, 25 received standard
      chemotherapy, with a 2-year overall survival (OS) rate of 100% and a 2-year event
      free survival (EFS) rate of 88%. Of the 26 pathological samples, 18 (70%) came
      from bone tissue, and the positive rate of BRAF-V600E mutation reached 50%
      (13/26). The positive rate of BRAF-V600E gene mutation was not associated with
      age, sex, affected organ, clinical classification, early treatment response,
      recurrence, and 2-year OS and EFS rates of the children with LCH (P>0.05), but it
      was associated with clinical grouping of LCH (P<0.05). CONCLUSIONS: Children with
      LCH tend to have a high OS rate and a high incidence rate of BRAF-V600E mutation.
      BRAF-V600E mutation is associated with clinical grouping of LCH.

PMID- 29658454
TI  - [Clinical features and prognosis of malignancy-associated hemophagocytic
      lymphohistiocytosis in children: a clinical analysis of 24 cases].
AB  - OBJECTIVE: To investigate the clinical features and prognosis of malignancy
      associated hemophagocytic lymphohistiocytosis (MAHS) in children. METHODS: A
      retrospective analysis was performed for the primary diseases, clinical features,
      and prognosis of 24 children with MAHS. RESULTS: Among the 24 children, 11 (46%)
      had MAHS induced by tumor and 13 (54%) had chemotherapy-associated MAHS. As for
      primary diseases, 17 children had acute leukemia, 6 had lymphoma, and 1 had
      neuroblastoma. The most common clinical manifestations were pyrexia, respiratory
      symptoms, and hepatosplenomegaly. The most common laboratory abnormalities were
      hemocytopenia, elevated serum ferritin, and elevated lactate dehydrogenase. Of
      the 24 children, 22 were treated according to the HLH-2004 protocol and 2 gave up
      treatment; 18 children died, 1 was lost to follow-up, and 5 survived. The
      survival time ranged from 3 days to 2 years and 4 months (median 28 days).
      CONCLUSIONS: Children with MAHS have various clinical features and extremely poor
      treatment outcomes.

PMID- 29658455
TI  - [Efficacy of early treatment via fiber bronchoscope in children with Mycoplasma
      pneumoniae pneumonia complicated by airway mucus obstruction].
AB  - OBJECTIVE: To study the efficacy of early treatment via fiber bronchoscope in
      children with Mycoplasma pneumoniae pneumonia (MPP) complicated by airway mucus
      obstruction. METHODS: According to the time from admission to the treatment via
      fiber bronchoscope, the children with MPP who were found to have airway mucus
      obstruction under a fiber bronchoscope were randomly divided into early
      intervention group (&le;3 days; n=40) and late intervention group (>3 days;
      n=56). The two groups were compared in terms of clinical data and imaging
      recovery.The children were followed for 1-3 months. RESULTS: Of the 96 children,
      38 were found to have the formation of plastic bronchial tree, among whom 10 were
      in the early intervention group and 28 were in the late intervention group
      (P=0.01). Compared with the late intervention group, the early intervention group
      had a shorter duration of fever, length of hospital stay, and time to the
      recovery of white blood cell count and C-reactive protein (P<0.05), as well as a
      higher atelectasis resolution rate (P<0.05). Compared with the late intervention
      group, the early intervention group had a higher percentage of children with a
      &ge; 60% absorbed area of pulmonary consolidation at discharge. After 3 months of
      follow-up, the early intervention group had a higher percentage of children with
      a &ge; 90% absorbed area of pulmonary consolidation than the late intervention
      group (80% vs 55%; P=0.01), and the early intervention group had a lower
      incidence rate of atelectasis than the late intervention group (P<0.05).
      CONCLUSIONS: Early treatment via fiber bronchoscope can shorten the course of the
      disease and reduce complications and sequelae in MPP children with airway mucus
      obstruction.

PMID- 29658456
TI  - [Predictive value of cord blood 25(OH)D3 for early infantile atopic dermatitis].
AB  - OBJECTIVE: To explore the predictive value of cord blood 25(OH)D3 [25(OH)D3] for
      infantile atopic dermatitis (AD), and to provide a reference for primary
      prevention of early infantile AD. METHODS: The neonates born from July to
      September, 2015 were enrolled. The cord blood samples were collected at birth to
      measure the level of 25(OH)D3. Outpatient follow-up was conducted for all the
      infants at 6 weeks, 3 months, and 6 months after birth. A survey was performed to
      investigate the incidence of AD. RESULTS: A total of 67 neonates completed a 6
      month follow-up. The incidence of AD was 34% (23/67), and 91% (21/23) of these
      cases occurred in the first month after birth. The 23 AD children had a
      significantly lower cord 25(OH)D3 level than those without AD (P<0.05). The
      children with a cord 25(OH)D3 level <30 nmol/L showed a significantly higher
      incidence of AD than those with a cord 25(OH)D3 level &ge;30 nmol/L (P<0.05). The
      receiver operating characteristic (ROC) analysis showed that the area under the
      ROC curve of cord 25(OH)D3 in predicting AD was 0.648 (standard error: 0.075;
      95%CI: 0.502-0.795). Its sensitivity, specificity, positive predictive value, and
      negative predictive value were 52.2%, 79.5%, 57.1%, and 76.1%, respectively.
      Logistic regression analysis showed that low cord 25(OH)D3 level, preference for
      seafood during pregnancy, atopic family history, and mixed feeding were risk
      factors for infantile AD (P<0.05). CONCLUSIONS: Cord 25(OH)D3 level is inversely
      associated with the risk of infantile AD, but it has a low diagnostic value for
      this disease.

PMID- 29658457
TI  - [Association between copy number variations and risk of overweight/obesity among
      Han, Uyghur, and Kazak children].
AB  - OBJECTIVE: To study the association between the prevalence of overweight/obesity
      and copy number variations (CNVs) among Han, Uyghur, and Kazak children in
      Xinjiang, China. METHODS: The kindergartens in Ili, Altay, and Karamay in
      Xinjiang were selected as research sites, and stratified cluster sampling was
      used to select the children aged 3-7 years. Body height and body weight were
      measured, and exfoliated buccal mucosa cells were collected. CNVplex(r) was used
      to measure the CNVs of FTO_1, IRX3_1, IRX3_2, MC4R_1, and MC4R_2. RESULTS: A
      total of 603 children were surveyed (307 boys and 296 girls). There were 261 Han
      children, 194 Uyghur children, and 148 Kazak children. The overweight/obesity
      rates in Han, Uyghur, and Kazak children were 28.3%, 10.3%, and 31.1%,
      respectively (P<0.001). In Kazak children, the CNVs of IRX3_1 and MC4R_2 were
      associated with overweight/obesity (P<0.05). The multivariate logistic regression
      analysis showed that the risk of overweight/obesity in Han and Kazak children was
      3.443 times (95%CI: 2.016-5.880) and 3.924 times (95%CI: 2.199-7.001),
      respectively, that in Uyghur children. The CNV of IRX3_1 was a risk factor for
      overweight/obesity (P=0.028, OR=2.251, 95%CI: 1.418-5.651). CONCLUSIONS: The CNV
      of IRX3_1 is associated with overweight/obesity in Han, Uyghur, and Kazak
      children, and the association between the CNV of IRX3_1 and overweight/obesity in
      Kazak children should be taken seriously.

PMID- 29658458
TI  - [Verbal and visual-spatial memory in Chinese children with developmental
      dyslexia].
AB  - OBJECTIVE: To explore the abilities of verbal and visual-spatial memory in
      Chinese children with developmental dyslexia. METHODS: Thirty-two children with
      developmental dyslexia (aged 8-12 years) and thirty-nine age- and gender-matched
      normal children were involved in the study. Their verbal short-term and verbal
      working memories were measured using the digit ordering and the digit span tests,
      respectively. Their visual-spatial short-term and visual-spatial working memories
      were examined using the forward and backward block-tapping tests, respectively.
      RESULTS: The DD children scored lower in the digit ordering and the digit span
      tests than the control children (P<0.05). The scores for the forward and backward
      block-tapping tests did not vary between the two groups (P>0.05). CONCLUSIONS:
      The children with DD have the deficits in both verbal short-term memory and
      verbal working memory.

PMID- 29658459
TI  - [Effect of ceftriaxone on the intestinal epithelium and microbiota in neonatal
      mice].
AB  - OBJECTIVE: To investigate the effect of ceftriaxone on the intestinal epithelium
      and microbiota in mice in the early-life stage, as well as the recovery of the
      intestinal epithelium and reconstruction of intestinal microbiota in adult mice.
      METHODS: A total of 36 BALB/C neonatal mice were randomly divided into control
      group and experimental group, with 18 mice in each group. The mice in the
      experimental group were given ceftriaxone 100 mg/kg every day by gavage within 21
      days after birth. Those in the control group were given an equal volume of normal
      saline by gavage. Immunohistochemistry was used to measure the expression of
      Ki67, Muc2, and ZO-1 in the intestinal epithelium. qPCR and next-generation
      sequencing were used to analyze the overall concentration and composition of
      fecal bacteria. RESULTS: After 21 days of ceftriaxone intervention, the
      experimental group had a significant reduction in body weight, a significant
      reduction in the expression of Ki67 and ZO-1 and a significant increase in the
      expression of Muc2 in intestinal epithelial cells, a significant reduction in the
      overall concentration of fecal bacteria, and a significant increase in the
      diversity of fecal bacteria compared with the control group (P<0.05). Firmicutes
      was the most common type of fecal bacteria in the experimental group, and there
      were large amounts of Staphylococcus and Enterococcus. The experimental group had
      a certain degree of recovery of the intestinal epithelium, but there were still
      significant differences in body weight and the structure of intestinal microbiota
      between the two groups at 56 days after birth (P<0.05). CONCLUSIONS: Early
      ceftriaxone intervention significantly affects the development of the intestinal
      epithelium and the construction of intestinal microbiota in the early-life stage.
      The injury of the intestinal microbiota in the early-life stage may continue to
      the adult stage and affect growth and development and physiological metabolism.

PMID- 29658460
TI  - [Neuroprotective effects of oligodendrocyte precursor cells on white matter
      damage in preterm infants].
AB  - White matter damage, characterized by demyelination due to the damage of
      oligodendrocyte precursor cells (OPCs), is the most common type of brain damage
      in preterm infants. Survivors are often subject to long-term neurodevelopmental
      sequelae because of the lack of effective treatment. In recent years, it has been
      found that cell transplantation has the potential for the treatment of white
      matter damage. OPCs are frequently used cells in cell transplantation therapy.
      With abilities of migration and myelinization, OPCs are the best seed cells for
      the treatment of white matter damage. Several studies have found that OPCs may
      not only replace impaired cells to reconstruct the structure and function of
      white matter, but also inhibit neuronal apoptosis, promote the proliferation of
      endogenous neural stem cells, and enhance the repairment of the blood-brain
      barrier. However, the clinical application of OPC transplantation therapy faces
      many challenges, such as the effectiveness, risk of tumorigenesis and immune
      rejection. With reference to these studies, this article reviewed the development
      of myelination, the obtainment of OPCs, the therapeutic mechanism as well as
      application research, and analyzed the current challenges of OPC transplantation,
      in order to provide a new direction for clinical treatment of white matter damage
      in preterm infants.

PMID- 29658461
TI  - [Monitoring of kidney injury in preterm infants].
AB  - Acute kidney injury (AKI) is a common complication in the neonatal intensive care
      unit that causes a high mortality of preterm infants and various chronic kidney
      diseases in adulthood. Preterm infants have immature development of the kidneys
      at birth. The kidneys continue to develop within a specific time window after
      birth. However, due to various factors during pregnancy and after birth, preterm
      infants tend to develop AKI. At present, serum creatinine and urine volume are
      used for the assessment of kidney injury, and their early sensitivity and
      specificity have attracted increasing attention. In recent years, various new
      biomarkers have been identified for early recognition of AKI. This article
      reviews the features, risk factors, renal function assessment, and
      prevention/treatment of AKI of preterm infants, in order to provide a reference
      for improving early diagnosis and treatment of AKI in preterm infants and long
      term quality of life.

PMID- 29658463
TI  - [Preserving humanity in tomorrow's medicine].

PMID- 29658462
TI  - [Research advances in immune tolerance of allogeneic cell transplantation in
      preterm infants].
AB  - Preterm infants are a special group, and related severe neurological,
      respiratory, and digestive disorders have high disability/fatality rates.
      Allogeneic cell transplantation may be an effective method for the prevention and
      treatment of these diseases. At present, animal studies have been conducted for
      allogeneic cell transplantation in the treatment of hypoxic-ischemic
      encephalopathy, bronchopulmonary dysplasia, and necrotizing enterocolitis. The
      main difficulty of this technique is graft-versus-host reaction (GVHR), and
      successful induction of immune tolerance needs to be achieved in order to solve
      this problem. This article reviews the research advances in immune tolerance of
      allogeneic cell transplantation in preterm infants.

PMID- 29658464
TI  - [Modulation by SUMO of PKR activation and stability].

PMID- 29658465
TI  - [Hypothalamic endospanin 1 dissociates obesity from type 2 diabetes].

PMID- 29658466
TI  - [Immunophage synergy is required for successful pulmonary phage therapy].

PMID- 29658467
TI  - [The enigmatic IgD class switch recombination].

PMID- 29658468
TI  - [Adipocyte cannabinoid receptor CB1: a relevant target for obesity!]

PMID- 29658469
TI  - [R-loop-associated genetic instability: why introns matter?]

PMID- 29658470
TI  - [Small but sturdy: neuronal-derived exosomes control brain vasculature
      integrity].

PMID- 29658471
TI  - [P-bodies: microscopic droplets to store mRNAs encoding regulatory proteins].

PMID- 29658473
TI  - ?

PMID- 29658472
TI  - [Evidence for the widespread use of neonatal screening for sickle cell disease].

PMID- 29658474
TI  - [Prospects for applications in human health of nanopore-based sequencing].
AB  - High throughput sequencing has opened up new clinical opportunities moving
      towards a medicine of precision. Oncology, infectious diseases or human genomics,
      many applications have been developed in recent years. The introduction of a
      third generation of nanopore-based sequencing technology, addressing some of the
      weaknesses of the previous generation, heralds a new revolution. Portability,
      real time, long reads and marginal investment costs, these promising new
      technologies point to a new shift of paradigm. What are the perspectives opened
      up by nanopores for clinical applications?

PMID- 29658475
TI  - [Aerobic glycolysis activation through canonical WNT/beta-catenin pathway in
      ALS].
AB  - Energy is the major determinant of neuronal viability. We focus our synthesis on
      the hypothesis of the development of aerobic glycolysis by the stimulation of the
      canonical WNT/beta-catenin pathway in amyotrophic lateral sclerosis (ALS). The
      stimulation of the canonical WNT/beta-catenin pathway induces the activation of
      aerobic glycolysis, also called Warburg effect, via the stimulation of glycolytic
      enzymes such as Glut (glucose transporter), PKM2 (pyruvate kinase M2), PDK1
      (pyruvate dehydrogenase kinase 1), LDH-A (lactate dehydrogenase A) and MCT-1
      (monocarboxylate transporter 1). The aerobic glycolysis consists to a supply of a
      large part of glucose into lactate regardless of oxygen. Aerobic glycolysis is
      less efficient in terms of ATP production than oxidative phosphorylation due to
      the shunt of the TCA cycle. Dysregulation of cellular energy metabolism promotes
      cell death and participates to the progression of ALS. Controlling the expression
      of the canonical WNT/beta-catenin signaling pathway is an attractive strategy to
      regulate aerobic glycolysis initiation and the progression of ALS.

PMID- 29658476
TI  - [Microbiota establishment: an in utero colonization decisive for future health?]
AB  - Some diseases seem to have a developmental origin. Today, the microbiota is
      recognized as a determinant in health and diseases and one important step is its
      establishment in the neonate. Some variations in its composition including an
      imbalance (also called dysbiosis) have been associated to several pathologies.
      Recent studies suggest a bacterial colonization in the non-pregnant uterus, in
      the amniotic fluid and in the placenta, which were previously thought sterile.
      So, during deve-lopmental phases, the fetus could have encounter bacteria in
      utero. These bacteria could contribute to its microbiota establishment before
      parturition and therefore before the encounter with all microorganisms from
      vaginal, fecal and cutaneous microbiotas according to the delivery mode. However,
      studies stating the existence of such in utero microbiota, characterized by a low
      biomass, are somewhat disputed.

PMID- 29658477
TI  - [PMNDTR mice: a new model to study neutrophils in vivo].
AB  - Neutrophils play a key role in host defense against pathogens. They can
      contribute to pathological inflammation, and are thought to exacerbate tissue
      injury upon exposure to bacterial products, such as endotoxin (LPS). Recent
      findings suggest that neutrophils can also participate in adaptive immune
      responses and contribute to inflammation resolution. Many discoveries regarding
      the in vivo role of neutrophils were made possible by the use of genetically
      modified neutrophil-deficient mice, or by the use of neutrophil-depleting
      antibodies. Here we describe a new mouse model, PMNDTR mice, in which neutrophils
      can be selectively depleted upon injection of diphtheria toxin. Using this model,
      we have recently demonstrated that neutrophils play a protective role during
      lethal endotoxin-induced systemic shock. This new mouse model presents several
      major advantages over more classical models of neutropenia, which are discussed
      herein.

PMID- 29658478
TI  - ?

PMID- 29658480
TI  - [Why are new drugs so expensive?]
AB  - Putting an end to an innovation crisis, the reality of which is the subject of
      debate, recent pharmaceutical innovations, the result of a combination of
      scientific, industrial, financial, political and economic reasons, lead to a
      diversification of products and to a strong interest of pharmaceutical companies
      for the so-called "niche" products (targeted therapies, rare diseases, etc.).
      These new molecules are put on the market at much higher prices than in the past.
      In the absence of reliable information on the costs borne by manufacturers, and
      knowing that high levels of margins have been observed, these prices raise
      legitimate questions. These are also motivated by the lack of relationship
      between the price and the therapeutic benefit of these new molecules. In France,
      faced with levels of expenditure likely to weaken the financial sustainability of
      the social protection system, the public authorities have so far always favored
      interventions on prices or the conditions and volume of reimbursement, in
      accordance with the existing regulation. Other regulations (use of the statutory
      license, group purchase, etc.) could in the future be used in a growing concern
      for the efficiency of public expenditure. The difficulties encountered in
      regulating a deeply transformed industrial sector call for a reform of national
      evaluation and regulation systems.

PMID- 29658479
TI  - [The zebrafish model in oncology].
AB  - Although cell culture and mouse models will remain a cornerstone of cancer
      research, the unique capabilities of the zebrafish outline the potential of this
      model for shedding light on cancer biology in vivo. Zebrafish develops cancers
      spontaneously, after chemical mutagenesis or through genetic manipulations.
      Furthermore, zebrafish cancers are similar to human tumors at the histological
      and molecular levels allowing the study of tumor initiation, progression and
      heterogeneity. Xenotransplantation of human cancer cells in embryos or adult
      zebrafish presents the advantage of following cancer cell behavior in vivo.
      Finally, zebrafish embryos are used in molecule screens and contribute to the
      identification of novel anti-cancer therapeutic strategies. Here, we review
      different involvements of the zebrafish model in cancer research.

PMID- 29658481
TI  - [Screening for asymptomatic cancers?]
AB  - A recent publication describes a sophisticated "liquid biopsy" procedure that
      analyses both tumoral DNA and proteins present in peripheral blood to provide
      sensitive detection of different types of cancer. These results represent a
      significant advance, but they still fall short of the sensitivity and specificity
      required, and it seems unlikely that they could progress to a level at which
      screening of the (asymptomatic) general population would have a really favourable
      benefit to risk ratio.

PMID- 29658482
TI  - Multidisciplinary care for better clinical outcomes: role of pharmacists in
      medication management.

PMID- 29658483
TI  - Bacteriology and risk factors associated with periprosthetic joint infection
      after primary total knee arthroplasty: retrospective study of 2543 cases.
AB  - INTRODUCTION: Periprosthetic joint infection after total knee arthroplasty is a
      serious complication. This study aimed to identify risk factors and
      bacteriological features associated with periprosthetic joint infection after
      primary total knee arthroplasty performed at a teaching hospital. METHODS: We
      reviewed 2543 elective primary total knee arthroplasties performed at our
      institution from 1993 to 2013. Data were collected from the Hong Kong Hospital
      Authority's Clinical Data Analysis and Reporting System, the Infection Control
      Team, and the joint replacement division registry. The association between
      potential risk factors and periprosthetic joint infection was examined by
      univariable analysis and multivariable logistic regression. Univariable analyses
      were also performed to examine the association between potential risk factors and
      bacteriology and between potential risk factors, including bacteriology, and
      early-onset infection. RESULTS: The incidence of periprosthetic joint infection
      in our series was 1.34% (n=34). The incidence of early-onset infection was 0.39%
      (n=24). Of the periprosthetic joint infections, 29.4% were early-onset
      infections. In both univariable and multivariable analyses, only rheumatoid
      arthritis was a significant predictor of periprosthetic joint infection.
      Methicillin-sensitive Staphylococcus aureus was the most common causative
      organism. We did not identify any significant association between potential risk
      factors and bacteriology. Periprosthetic joint infection caused by skin flora was
      positively associated with early-onset infection but the association was not
      statistically significant. CONCLUSION: The incidence of periprosthetic joint
      infection after elective primary total knee arthroplasty performed at our
      institution from 1993 to 2013 was 1.34%. Rheumatoid arthritis was a significant
      risk factor for periprosthetic joint infection.

PMID- 29658484
TI  - Complexity of syncope in elderly people: a comprehensive geriatric approach.
AB  - Syncope is a prevalent health problem among elderly people. It may be neurally
      mediated or caused by conditions such as orthostatic hypotension, postprandial
      hypotension, and cardiac disorders. A combination of different aetiologies is not
      uncommon in the elderly people. Many pathophysiological processes, including age
      related physiological changes, co-morbidities, concomitant medication use, and
      prolonged bedrest, coexist and predispose elderly people to syncope; advanced age
      and cardiac syncope are associated with increased mortality. Recurrent syncope
      and its co-morbidities, such as fall-related physical injury, negative
      psychological impact, and functional decline, may increase the dependency of
      elderly patients. Furthermore, the overlap between falls and syncope, and the
      interaction between syncope and frailty complicate management. Available clinical
      guidelines for the management of syncope that focus on diagnosis, investigation,
      and treatment are therefore insufficient to address syncope in elderly patients.
      A comprehensive geriatric approach that considers an individual's functional and
      cognitive capacities, as well as medical and psychosocial aspects, would be more
      appropriate.

PMID- 29658485
TI  - Hyperbaric oxygen therapy: its use in medical emergencies and its development in
      Hong Kong.
AB  - Hyperbaric oxygen therapy is widely accepted as life-saving treatment for
      decompression illness. Yet its use in acute carbon monoxide poisoning has
      remained controversial because of inconsistent findings in clinical trials.
      Hyperbaric oxygen therapy has an adjunctive role in managing gas gangrene,
      necrotising soft-tissue infection, and crush injury, as supported by case series.
      Several cases have been reported in the literature detailing the use of
      hyperbaric oxygen therapy in patients with severe anaemia in whom blood
      transfusion is not possible. Today, use of hyperbaric oxygen therapy in Hong Kong
      is limited by low awareness among physicians and patients, a lack of service
      access, and inadequate hospital and critical care support for the existing non
      hospital facility. The recent introduction of a hospital-based facility is
      expected to benefit more patients for whom hyperbaric oxygen therapy is
      appropriate. This article reviews the mechanistic basis of and emerging
      scientific evidence to support the use of hyperbaric oxygen therapy in a number
      of acute medical emergencies, as well as the past and future development of
      hyperbaric oxygen therapy in Hong Kong.

PMID- 29658486
TI  - Familial eruptive syringoma.

PMID- 29658487
TI  - Cystic artery pseudoaneurysm with haemobilia after laparoscopic cholecystectomy.

PMID- 29658488
TI  - Pancreatic pseudocyst rupture into the portal vein diagnosed by magnetic
      resonance imaging.

PMID- 29658489
TI  - Characteristic imaging features of clonorchiasis.

PMID- 29658490
TI  - Pleural adenosine deaminase cut-off value for the diagnosis of tuberculous
      pleural effusion using the Diazyme assay.

PMID- 29658491
TI  - GPU-based Green's function simulations of shear waves generated by an applied
      acoustic radiation force in elastic and viscoelastic models.
AB  - Shear wave calculations induced by an acoustic radiation force are very time
      consuming on desktop computers, and high-performance graphics processing units
      (GPUs) achieve dramatic reductions in the computation time for these simulations.
      The acoustic radiation force is calculated using the fast near field method and
      the angular spectrum approach, and then the shear waves are calculated in
      parallel with Green's functions on a GPU. This combination enables rapid
      evaluation of shear waves for push beams with different spatial samplings and for
      apertures with different f/#. Relative to shear wave simulations that evaluate
      the same algorithm on an Intel i7 desktop computer, a high performance nVidia GPU
      reduces the time required for these calculations by a factor of 45 and 700 when
      applied to elastic and viscoelastic shear wave simulation models, respectively.
      These GPU-accelerated simulations also compared to measurements in different
      viscoelastic phantoms, and the results are similar. For parametric evaluations
      and for comparisons with measured shear wave data, shear wave simulations with
      the Green's function approach are ideally suited for high-performance GPUs.

PMID- 29658492
TI  - Modeling the cost and benefit of proteome regulation in a growing bacterial cell.
AB  - Escherichia coli cells differentially regulate the production of metabolic and
      ribosomal proteins in order to stay close to an optimal growth rate in different
      environments, and exhibit the bacterial growth laws as a consequence. We present
      a simple mathematical model of a growing-dividing cell in which an internal
      dynamical mechanism regulates the allocation of proteomic resources between
      different protein sectors. The model allows an endogenous determination of the
      growth rate of the cell as a function of cellular and environmental parameters,
      and reproduces the bacterial growth laws. We use the model and its variants to
      study the balance between the cost and benefit of regulation. A cost is incurred
      because cellular resources are diverted to produce the regulatory apparatus. We
      show that there is a window of environments or a 'niche' in which the unregulated
      cell has a higher fitness than the regulated cell. Outside this niche there is a
      large space of constant and time varying environments in which regulation is an
      advantage. A knowledge of the 'niche boundaries' allows one to gain an intuitive
      understanding of the class of environments in which regulation is an advantage
      for the organism and which would therefore favour the evolution of regulation.
      The model allows us to determine the 'niche boundaries' as a function of cellular
      parameters such as the size of the burden of the regulatory apparatus. This class
      of models may be useful in elucidating various tradeoffs in cells and in making
      in-silico predictions relevant for synthetic biology.

PMID- 29658493
TI  - Novel inter-crystal scattering event identification method for PET detectors.
AB  - Here, we propose a novel method to identify inter-crystal scattering (ICS) events
      from a PET detector that is even applicable to light-sharing designs. In the
      proposed method, the detector observation was considered as a linear problem and
      ICS events were identified by solving this problem. Two ICS identification
      methods were suggested for solving the linear problem, pseudoinverse matrix
      calculation and convex constrained optimization. The proposed method was
      evaluated based on simulation and experimental studies. For the simulation study,
      an 8  *  8 photo sensor was coupled to 8  *  8, 10  *  10 and 12  *  12 crystal
      arrays to simulate a one-to-one coupling and two light-sharing detectors,
      respectively. The identification rate, the rate that the identified ICS events
      correctly include the true first interaction position and the energy linearity
      were evaluated for the proposed ICS identification methods. For the experimental
      study, a digital silicon photomultiplier was coupled with 8  *  8 and 10  *  10
      arrays of 3  *  3  *  20 mm3 LGSO crystals to construct the one-to-one coupling
      and light-sharing detectors, respectively. Intrinsic spatial resolutions were
      measured for two detector types. The proposed ICS identification methods were
      implemented, and intrinsic resolutions were compared with and without ICS
      recovery. As a result, the simulation study showed that the proposed convex
      optimization method yielded robust energy estimation and high ICS identification
      rates of 0.93 and 0.87 for the one-to-one and light-sharing detectors,
      respectively. The experimental study showed a resolution improvement after
      recovering the identified ICS events into the first interaction position. The
      average intrinsic spatial resolutions for the one-to-one and light-sharing
      detector were 1.95 and 2.25 mm in the FWHM without ICS recovery, respectively.
      These values improved to 1.72 and 1.83 mm after ICS recovery, respectively. In
      conclusion, our proposed method showed good ICS identification in both one-to-one
      coupling and light-sharing detectors. We experimentally validated that the ICS
      recovery based on the proposed identification method led to an improved
      resolution.

PMID- 29658495
TI  - Internal Hernia Following Robotic Assisted Pancreaticoduodenectomy.
AB  - BACKGROUND Robotic assisted pancreaticoduodenectomy (RPD) is reported to be safe
      and feasible. Internal hernia (IH) after RPD is a serious but rarely reported
      complication. MATERIAL AND METHODS We retrospectively reviewed data of 231
      patients who underwent RPD from October 2010 to December 2016. The incidence,
      symptoms, time of presentation, and outcome were investigated. RESULTS Five
      patients (2.6%) were diagnosed with IH. Significant correlation (P<0.001) between
      IH and transverse mesocolon defect was confirmed. In patients without defect
      closure, the incidence of IH was 62.5%, while patients who received defect
      closure experienced no IH. The median time between initial surgery and occurrence
      of IH was 76 days. The main symptoms were abdominal pain, nausea, and vomiting.
      All patients received abdominal computed tomography (CT) and were suspected to
      have IH according to imaging and symptoms. All patients underwent reoperation (2
      laparoscopic and 3 open surgery). The median length of hospital stay was 13 days.
      No patient experienced a relapse after treatment. CONCLUSIONS Abdominal pain,
      nausea, and vomiting were common symptoms in our study patients who underwent
      RPD. IH should be suspected if there is a positive finding on CT. Timely
      reoperation is necaAbdominal pain, nausea, and vomiting were common symptoms in
      our study patients who underwent RPD. IH should be suspected if there is a
      positive finding on CT. Timely reoperation is necessary because IH may cause
      intestinal ischemia. Meticulous closure of the mesenteric defect is vital to
      avoid IH.essary because IH may cause intestinal ischemia. Meticulous closure of
      the mesenteric defect is vital to avoid IH.

PMID- 29658496
TI  - [GESTASTRES cohort study protocol on the effects of stress during pregnancy by
      measuring the cortisol in women's and newborn's hair].
AB  - The aim was to present the longitudinal study protocol on the effects of
      perinatal stress from conception to one year of age. Stress is associated to
      psychopathological, cardiovascular and inmunological diseases. During pregnancy,
      the activation of the Hipotalamic-Pituitary-Adrenal results in an increased
      release of cortisol. Stress during pregnancy is related to maternal, fetal and
      infant negative outcomes that can last a lifetime. Nevertheless, contradictory
      findings have been reported. In this longitudinal study maternal stress is
      assessed from a sample of 807 pregnant women through hair cortisol levels and
      psychological question- naires during the three trimesters of pregnancy. Besides,
      associa- tions with the new-borns' hair cortisol levels, temperament and
      neurodevelopment at age 6 and 12 months are assessed. Sociode- mographic,
      obstetrics, delivery, fetal and newborn development variables are included in
      analysis. Findings will be able to pro- vide a better understanding of perinatal
      stress and will improve maternal, fetal and infant outcomes.

PMID- 29658494
TI  - Multi-resolution simulation of focused ultrasound propagation through ovine skull
      from a single-element transducer.
AB  - Transcranial focused ultrasound (tFUS) is emerging as a non-invasive brain
      stimulation modality. Complicated interactions between acoustic pressure waves
      and osseous tissue introduce many challenges in the accurate targeting of an
      acoustic focus through the cranium. Image-guidance accompanied by a numerical
      simulation is desired to predict the intracranial acoustic propagation through
      the skull; however, such simulations typically demand heavy computation, which
      warrants an expedited processing method to provide on-site feedback for the user
      in guiding the acoustic focus to a particular brain region. In this paper, we
      present a multi-resolution simulation method based on the finite-difference time
      domain formulation to model the transcranial propagation of acoustic waves from a
      single-element transducer (250 kHz). The multi-resolution approach improved
      computational efficiency by providing the flexibility in adjusting the spatial
      resolution. The simulation was also accelerated by utilizing parallelized
      computation through the graphic processing unit. To evaluate the accuracy of the
      method, we measured the actual acoustic fields through ex vivo sheep skulls with
      different sonication incident angles. The measured acoustic fields were compared
      to the simulation results in terms of focal location, dimensions, and pressure
      levels. The computational efficiency of the presented method was also assessed by
      comparing simulation speeds at various combinations of resolution grid settings.
      The multi-resolution grids consisting of 0.5 and 1.0 mm resolutions gave
      acceptable accuracy (under 3 mm in terms of focal position and dimension, less
      than 5% difference in peak pressure ratio) with a speed compatible with semi real
      time user feedback (within 30 s). The proposed multi-resolution approach may
      serve as a novel tool for simulation-based guidance for tFUS applications.

PMID- 29658497
TI  - [Addictions profiles as a tool for comparison of chemical and nonchemical
      dependencies].
AB  - AIM: A clinical and phenomenological comparative evaluation of addictions
      (alcoholism, drug addiction, sexual and tobacco dependence, pathological
      gambling) to develop integrative methods for the assessment of comparative
      performance profiles of addictive disorders. MATERIAL AND METHODS: One hundred
      and forty-six patients were examined using clinical, psychometric and statistical
      methods. RESULTS AND CONCLUSION: Addiction profiles were described and addictive
      potentials were compared. The most pronounced addictive symptoms were found in
      groups where the participants were addicted to drugs or to pathological gambling.
      The least pronounced symptoms were found in patients addicted to tobacco.
      Participants addicted to alcohol were in the middle range.

PMID- 29658498
TI  - [Clinical symptoms and personality traits in patients using psychostimulant drugs
      and other psychoactive substances].
AB  - AIM: To obtain preliminary data on personality and clinical/psychopathological
      predictors of combined use of psychoactive drugs in patients with psychostimulant
      dependence. MATERIAL AND METHODS: Eighty-nine inpatients were examined. Family
      history of drug dependence, personality disorders, clinical/psychopathological
      characteristics and disease course (breakdowns, relapses, remissions) were
      compared in patients with psychostimulant dependence (n=35) and patients who used
      other psychoactive substances (n=54). RESULTS AND CONCLUSION: Combined use of
      psychoactive substances is predicted by a complex of factors, including genetic,
      biological (neurochemical), psychological (personality characteristics of
      comorbidity and social influences). Based on their proportion, three types of
      psychostimulant dependence were determined.

PMID- 29658499
TI  - [The impact of abuse and neglect in childhood on the development of substance use
      disorders].
AB  - The review of literature over the last decade addresses the impact of childhood
      abuse and neglect on the further development of addictions and mental disorders.
      The results of the studies have been analyzed in the aspect of abuse, age and
      gender characteristics in childhood and variants of consequences: from
      neurodevelopment to behavioral disorders. Childhood abuse and neglect is
      associated with the higher risk of posttraumatic stress disorder, suicidal
      behavior and some psychiatric diseases. Attention is focused on the fact that
      adults with substance use disorders (SUDs) report higher rates of child abuse
      than adults without SUDs. The problem demands further investigation to find
      possible predictors of substance use disorders in patients who had experienced
      stressful life events in childhood.

PMID- 29658500
TI  - [The relationship between the family structure and characteristics of the stress
      reaction in adolescent addicts].
AB  - AIM: To study the relationship between the family structure and characteristics
      of the response to stress in adolescent addicts. MATERIAL AND METHODS: The study
      included 65 patients who used psychoactive substances and 42 healthy controls. A
      set of psychological methods was used. RESULTS AND CONCLUSION: In the group of
      adolescent addicts, a low result was revealed on the scale 'family cohesion'. A
      high level of development of such mechanisms of psychological defense as denial,
      suppression, repression, compensation, substitution, intellectualization and
      reactive education was diagnosed in both groups. Significant differences were
      revealed only in repression. Such stress coping strategies as self-control,
      escape-avoidance and problem-solving were more often used in the main group while
      confrontational coping, distancing, seeking social support, accepting
      responsibility and positive reassessment were used in the control group. Lower
      indices of resilience in adolescent addicts compared to the control group.

PMID- 29658501
TI  - [Anhedonia, depression, anxiety, and craving in opioid dependent patients
      stabilized on oral naltrexone or naltrexone implant].
AB  - AIM: To assess the relationship between long-term naltrexone treatment and
      anxiety, depression and craving in opioid dependent individuals. MATERIAL AND
      METHODS: Opioid dependent patients (n=306) were enrolled in a three cell
      (102ss/cell) randomized, double blind, double dummy, placebo-controlled 6-month
      trial comparing extended release implantable naltrexone with oral naltrexone and
      placebo (oral and implant). Monthly assessments of affective responses used a
      Visual Analog Scale for opioid craving, the Beck Depression Inventory,
      Spielberger Anxiety Inventory, and the Ferguson and Chapman Anhedonia Scales.
      Between-group outcomes were analyzed using mixed model analysis of variance
      (Mixed ANOVA) and repeated measures and the post hoc Tukey test. RESULTS AND
      CONCLUSION: Anhedonia, depression, anxiety, and craving for opiates were elevated
      at baseline but gradually reduced to normal within the first 1-2 months for
      patients who remained in treatment and did not relapse. There were no significant
      between-group differences prior to treatment dropout as well as between those who
      relapsed and who continued on naltrexone. CONCLUSION: These data do not support
      concerns that naltrexone treatment of opioid dependence precipitates anhedonia,
      depression, anxiety or craving for opiates.

PMID- 29658502
TI  - [Treatment of anxiety disorders in alcohol abusers].
AB  - The tendency to anxiety is a characteristic feature of alcohol abusers, and
      anxiety can be a symptom of alcohol withdrawal as well as comorbid disorder. The
      frequent comorbidity of alcohol use disorders and anxiety is due to a number of
      reasons including general hereditary predisposition, mutual conditioning and
      similar pathogenesis. Pharmacological therapy of anxiety disorders in alcohol
      dependent patients is carried out on the basis of general principles of anxiety
      treatment and involves the use of benzodiazepines, antidepressants and, in some
      cases, antipsychotics as second-line medicines.

PMID- 29658504
TI  - [Alcohol withdrawal syndrome dynamics during treatment with nooclerin (deanoli
      aceglumas)].
AB  - AIM: To study the efficacy of nooclerin (deanoli aceglumas) in alcohol withdrawal
      syndrome assessed by clinical and biochemical characteristics. MATERIAL AND
      METHODS: A multicenter, open, randomized, comparative study of nooclerin in the
      complex treatment of alcohol withdrawal syndrome included 90 patients. The
      patients were randomized into nooclerin group (n=55) and control group (n=35).
      RESULTS AND CONCLUSION: Nooclerin reduced alcohol withdrawal symptoms more
      significantly throughout the whole study period. There were significant between
      group differences on the Clinical Institute Withdrawal Assessment of Alcohol
      Scale (CIWA-Ar) and the Multidimensional Fatigue Inventory (MFI-20). However,
      patients exhibited no excessive activity. No adverse side-effects were observed.

PMID- 29658503
TI  - [The safety and efficacy of alimemazine (teraligen) in relieving anxiety in
      patients with alcohol addiction].
AB  - AIM: To assess the efficacy of monotherapy of anxiety in alcoholism with
      alimemazine (teraligen). MATERIAL AND METHODS: Thirty-six patients with alcohol
      addiction were treated with alimemazine in dose 15 mg during 9 month. In control
      group (11 patients) teraligen was no used. RESULTS AND CONCLUSION: A significant
      positive effect of treatment with teraligen was observed. There were the
      improvement in alcohol addiction course, decrease in scores on the Addiction
      Severity Index (ASI) from severe to mild level and decrease in trait and state
      anxiety measured with the Spielberger-Khanin scale from high to low levels. The
      reduction on symptoms of depression from moderate (at baseline) to subdepressive
      levels on the Beck Depression Inventory was noted in the end of treatment.

PMID- 29658505
TI  - [The possibilities of neurostimulation (sympathetic correction) in the treatment
      of amnestic (Korsakoff's) psychosis].
AB  - AIM: To evaluate the efficacy of non-invasive multichannel electrical stimulation
      (sympathetic correction) in patients with alcohol amnesic (Korsakoff's)
      psychosis. MATERIAL AND METHODS: Thirty-seven men, aged 33-48 years, with
      Korsakoff's (amnestic) psychosis were studied. The duration of disease varied
      from 12 to 24 month. The device of electrical stimulation of neck nerve
      structures was used for neuroelectrostimulation. Treatment included 15 sessions
      within 3 weeks. During this period, patients did not receive pharmacological
      therapy. The Frontal Assessment Battery (FAB), the Montreal Cognitive Assessment
      (MoCA) and the Mini-Mental State Examination (MMSE) were used to determine
      changes in cognitive state of patients. Electroencephalography with qEEG analysis
      and spectral analysis of heart rate variability (HRV) were carried out as well.
      RESULTS AND CONCLUSION: Positive effects of treatment were observed in all
      patients that suggested the high therapeutic potential of the
      neuroelectrostimulation method.

PMID- 29658506
TI  - [The relationship between indicators of drug users detection and the population
      referral to drug treatment services].
AB  - AIM: To examine the relationship between the results of drug users'
      identification through medical examination for drug intoxication and the rates of
      primary population' referral for drug treatment. MATERIAL AND METHODS: The data
      of the state federal statistical observation for period of 2009-2013 were used.
      Methods of descriptive statistics and regression analysis were applied. RESULTS
      AND CONCLUSION: It has been established that the identification of drug users
      during medical examination of citizens for the state of drug intoxication has a
      statistically significant effect on the population' drug treatment referral
      rates. According to linear regression equations, out of each 100 cases identified
      through medical examination, only 15 patients referred to drug treatment
      services. From practical point of view, the influence of the first indicator on
      the second one is not high: an increase in the number of identified drug users
      for each 100 cases leads to an increase in referral rate of patients with drug
      dependence syndrome for 2 cases, while the referral rate of drug users with
      established diagnosis of the harmful use of drugs increases for 10 patients. The
      results of the study highlight the urgent need for developing secondary
      prevention programs for those diagnosed with the harmful use of drugs. There is
      also a question of further improvement of legislation in the field of law
      governed motivation of exposed drug users to seek drug treatment.

PMID- 29658507
TI  - [Causes, consequences and overcoming ways of stigmatization of patients with
      substance abuse disorders].
AB  - Stigmatization of people with drug and alcohol use disorders, its types and main
      causes of stigmatization have been analyzed. Main symptoms, types and
      consequences of stigmatization as for people with drug and alcohol abuse as well
      for society in whole have been described. Based on the complex of traits studied,
      the key causes and factors of stigma were analyzed and the variants of
      destigmatization of patients were suggested.

PMID- 29658508
TI  - [Psychosocial characteristics of alcohol dependence patients committed self
      poisoning suicide attempt].
AB  - AIM: To determine s psychosocial characteristics of alcohol-dependent patients
      committed self-poisoning suicide attempt. MATERIAL AND METHODS: Individuals, who
      were admitted to the toxicology department after the self-poisoning suicidal
      attempt, were studied. The socio-demographic, personal history data together with
      experimental psychological methods (V.P. Dvorschenko Personality Accentuation
      Test, AUDIT, Beck Hopelessness and Suicide Intention Scales, Barratt Impulsivity
      Scale) were used. RESULTS AND CONCLUSION: Individuals, who attempted suicide and
      abused alcohol, were characterized by the higher level of impulsivity, tendency
      to drug addiction, reduced ability to self-control and activity planning. They
      had excitable accentuation types and committed demonstrative suicidal attempts
      more often. Alcohol abuse was positively correlated with a tendency to drug
      addiction, impulsivity and was negatively correlated with the true suicide
      attempt and tendency to depression. Psychological characteristics of individuals
      with alcohol dependence committed suicide attempt differ from individuals without
      alcohol abuse.

PMID- 29658509
TI  - [Experimental approaches to the investigation of behavioral disorders associated
      with prenatal alcohol exposure].
AB  - Fetal alcohol spectrum disorders (FASD) is an umbrella term which covers a wide
      range of deficits in prenatal and postnatal growth, anatomy and CNS functions
      produced by prenatal alcohol exposure. The most severe form of FASD is fetal
      alcohol syndrome (FAS) characterized by additional specific craniofacial and
      brain malformations. Despite a high prevalence and extensive clinical studies,
      the fundamental mechanisms of FASD are still poorly understood. Thereby,
      experimental models, which allow better control for both socio-environmental and
      genetic factors, are critical to our understanding of FASD. The review is focused
      on the effects of exposure to alcohol during the prenatal period in animal
      models. The authors outline that prenatally alcohol-induced changes in motor and
      executive functions, learning and memory, stress reactivity and affective state
      are remarkably parallel between animals and humans. Finally, the authors consider
      a potential impact of postnatal social and environmental factors on the outcome
      in experimental models of FASD.

PMID- 29658511
TI  - Immunometabolism: Old drug, new trick.

PMID- 29658510
TI  - A protocol for quantizing total bacterial 16S rDNA in plasma as a marker of
      microbial translocation in vivo.

PMID- 29658514
TI  - Maternal or neonatal infection: association with neonatal encephalopathy
      outcomes.
AB  - This corrects the article DOI: 10.1038/pr.2014.47.

PMID- 29658513
TI  - B2 adrenergic receptor gene polymorphism effect on childhood asthma severity and
      response to treatment.
AB  - BackgroundAlterations of B2 adrenergic receptor (beta2AR) can modulate the
      severity of asthma and the response to treatment. Therefore, we aimed to evaluate
      beta2AR gene polymorphism at codons 16 and 27 and their effect on asthma severity
      and response to treatment in asthmatic children.MethodsCase-control study was
      conducted on 156 children; 104 of them had bronchial asthma and 52 were healthy
      children (control group). Subjects of the study underwent history taking,
      clinical examination, pulmonary function tests, serum IgE level assessment, and
      identification of beta2AR-16 A46G and beta2AR-27 C79G polymorphism using PCR
      Restriction Fragment length polymorphisms (RFLP) test.ResultsThere was a higher
      frequency of Arg-Gly genotypes (odds ratio (OR)=6.57; confidence interval (CI):
      2.42-18.81, P<0.001) and lower frequency of Arg-Arg (OR=4.7; CI: 2.05-10.95,
      P<0.001) among asthmatic children compared with that among controls at codon 16.
      The presence or absence of Gly16 or Glu27 either homozygous or heterozygous for
      both correlated with the grade of asthma severity. The presence of heterozygous
      Arg-Gly and Gln-Glu gives a better response to drug therapy than the presence of
      Gly-Gly and Glu-Glu genotypes at codons 16 and 27.ConclusionPolymorphism of
      beta2AR at codons 16 and 27 correlates with asthma severity and response to
      treatment in asthmatic children.

PMID- 29658515
TI  - Assessment of corneal and fatty tissues biomechanical response in dynamic
      tonometry tests by using inverse models.
AB  - PURPOSE: The assessment of corneal biomechanics is essential for studying
      ophthalmological operations, such as refractive surgeries, and for more accurate
      estimation of intraocular pressure. The chief aim of the current study is to
      characterize corneal and fatty tissues in order to construct a model to predict
      eye globe behavior during dynamic tonometry tests. METHODS: In the present study,
      images from corneal deformation, acquired from Corvis ST tonometer, were
      processed. Then, corneal pure displacement and eye globe retraction were
      calculated. Utilizing inverse finite element method, corneal material properties
      were calculated in order to predict pure deformation obtained from Corvis ST.
      Using a similar approach, material parameters of fatty tissue were estimated in
      order to predict the eye globe retraction. The model used for fatty tissue was
      considered as corneal boundary condition in a forward finite element model to
      create a joint model, which could simulate corneal behavior in dynamic tonometry
      tests. RESULTS: It was shown that an isotropic material model is accurate enough
      to predict corneal deformation in dynamic tonometry tests. Moreover, effects of
      IOP on the estimated material properties were investigated. Finally, utilizing
      the joint model, it was demonstrated that there is strong correlation between
      corneal stiffness and the biomechanical parameter introduced by Corvis ST.
      CONCLUSIONS: An eye globe model was constructed and characterized by two distinct
      inverse models for corneal and fatty tissue. This model can be utilized for
      predicting eye globe behavior during dynamic tonometry tests besides other
      ophthalmological operations.

PMID- 29658516
TI  - Optimization of differentiation time of mesenchymal-stem-cell to tenocyte under a
      cyclic stretching with a microgrooved culture membrane and selected measurement
      cells.
AB  - PURPOSE: There is a need for efficient stem cell-to-tenocyte differentiation
      techniques for tendon tissue engineering. More than 1 week is required for
      tenogenic differentiation with chemical stimuli, including co-culturing. Research
      has begun to examine the utility of mechanical stimuli, which reduces the
      differentiation time to several days. However, the precise length of time
      required to differentiate human bone marrow-derived mesenchymal stem cells
      (hBMSCs) into tenocytes has not been clarified. Understanding the precise time
      required is important for future tissue engineering projects. Therefore, in this
      study, a method was developed to more precisely determine the length of time
      required to differentiate hBMSCs into tenocytes with cyclic stretching stimulus.
      METHODS: First, it had to be determined how stretching stimulation affected the
      cells. Microgrooved culture membranes were used to suppress cell orientation
      behavior. Then, only cells oriented parallel to the microgrooves were selected
      and evaluated for protein synthesis levels for differentiation. RESULTS: The
      results revealed that growing cells on the microgrooved membrane and selecting
      optimally-oriented cells for measurement improved the accuracy of the
      differentiation evaluation, and that hBMSCs differentiated into tenocytes in
      approximately 10 h. CONCLUSIONS: The differentiation time corresponded to the
      time required for cellular cytoskeleton reorganization and cellular morphology
      alterations. This suggests that cells, when subjected to mechanical stimulus,
      secrete mRNAs and proteins for both cytoskeleton reorganization and
      differentiation.

PMID- 29658517
TI  - Balance disturbances coefficient as a new value to assess ability to maintain
      balance on the basis of FFT curves.
AB  - PURPOSE: The aim of this study was to formulate a new balance disturbances
      coefficient enabling objective balance assessment on the basis of fast Fourier
      transform curves. The article presents the method of coefficient calculation and
      possible ways of its interpretation. METHODS: 11 healthy participants took part
      in the experiment. There were four measurements: two in real environment with
      eyes open and eyes closed as well as two in virtual environment with scenery
      (surroundings) oscillating with frequency 0.7 Hz and 1.4 Hz. Scenery was
      displayed by means of the Oculus Rift system, whereas position of centre of
      pressure was measured with the use of Zebris FDM-S platform. Obtained centre of
      pressure positions were used to calculate fast Fourier transform, and then
      balance disturbances coefficient. RESULTS: Comparisons of coefficient values
      obtained for the whole group and two selected participants were presented in
      order to explain how to interpret and use the coefficient. For better explanation
      of coefficient interpretation the most popular time domain stabilometric
      quantities and fast Fourier transform curves were presented as well. CONCLUSIONS:
      The balance disturbances coefficient makes it possible to quantitatively and
      objectively determine, on the basis of fast Fourier transform curves, the
      influence of the oscillating scenery on the tested person as well as show how the
      overall equilibrium of that person was disturbed.

PMID- 29658519
TI  - Biomechanical evaluation of tendon connection with novel suture techniques.
AB  - PURPOSE: Achilles tendon rupture is a severe injury with poor curative effect due
      to its anatomical characteristic and mechanical peculiarity. Internal fixation of
      limited loop (IFLL) with steel-wire has been applied on patients with tendon
      rupture to fix the broken ends before physical rehabilitation. The purpose of
      this study is to investigate the biomechanical property and radiological
      characteristic of such suture technique for the repairment of tendon rupture.
      METHODS: Tendons of pigs' hint feet were separated for the biomechanical study.
      Suture surgery was performed according to the protocol of IFLL. Biomechanical
      Testing Machine was adopted to conduct the biomechanical tensile load
      examination. The maximal load, elastic modulus and tendon stiffness of the
      stitched tendons with or without reinforcement were examined. RESULTS: The
      maximum tensile load of the stitched tendons using IFLL reached 1/4 of the
      uninjured tendon's maximum tensile load, indicating that such suture technique is
      capable of providing enough tension for the ruptured tendon. Surprisingly,
      tendons fixed with titanium wire showed the highest load tension, which was
      comparable to the undamaged tendon. Therefore, we found the biomechanical basis
      of using IFLL in effectively connecting the rupture ends of tendons. CONCLUSIONS:
      In conclusion, we provide biomechanical evidence for the use of IFLL in treatment
      of Achilles tendon rupture, by providing enough strength for the ankle function.
      Such suture technique could help the patients with better rehabilitation and
      reduced in-hospital stay after Achilles tendon injury.

PMID- 29658518
TI  - Stabilometric indicators as an element of verifying rehabilitation of patients
      before and after reconstruction of anterior cruciate ligament.
AB  - PURPOSE: The aim of the study was to evaluate effectiveness of rehabilitation in
      patients before and after rACL, based on stabilographic indicators. METHODS: The
      research group was comprised of 31 men aged 20-57 with anterior cruciate ligament
      injury, qualified for reconstruction surgery. A measurement of static
      stabilometric indicators and muscle strength was taken twice for each patient -
      before surgery and after 6 months. To assess stabilographic indicators the
      stabilographic platform was used and to asses muscle strength a dynamometer was
      used. In order to assess knee function the Lysholm scale and VAS scale were used.
      RESULTS: The rehabilitation programme improved static stability of the knee in
      the frontal plane, which is manifested by a significant shortening of the SPML
      path length. Rehabilitation proceedings should focus on improving static
      stability of the knee joint in the sagittal plane, because the results obtained
      indicate only a slight shortening of the SPAP length. The results of the Lysholm
      and VAS scales point to a positive influence of the applied rehabilitation.
      CONCLUSION: Inclusion into rehabilitation diagnostic tools to assess
      stabilometric indicators enables for effective verification of rehabilitation
      proceedings focused on restoring body posture control before and after the rACL.

PMID- 29658520
TI  - Biomechanical characterization of slope walking using musculoskeletal model
      simulation.
AB  - PURPOSE: Upslope and downslope walking are basic activities necessary for normal
      daily living in community, and they impose greater joint load on the lower
      extremities than during level walking. Thus, the purpose of this study was to
      quantify the resultant and shear forces in the hip and knee joints during slope
      walking. METHODS: Twelve healthy volunteers were evaluated when walking under
      level and 10 degrees  up- and downslope conditions. Three-dimensional gait
      analysis was conducted using a 7-camera optoelectronic motion analysis system
      combined with a force plate to measure ground reactive force. Joint forces in the
      hip and knee joints were estimated using musculoskeletal model simulation.
      RESULTS: Results showed that the resultant hip force was increased significantly
      to 117.2% and 126.9%, and the resultant knee force was increased to 133.5% and
      144.5% in up- and downslope walking, respectively, compared to that of level
      walking. Furthermore, increased shear force in the hip and knee joints was noted
      during both slope walking conditions. CONCLUSIONS: This information may be
      beneficial for therapists advising elderly people or patients with osteoarthrosis
      on an appropriate gait pattern, gait assistive devices, or orthoses according to
      their living environment.

PMID- 29658521
TI  - Ratios of torques of antagonist muscle groups in female soccer players.
AB  - PURPOSE: An increase in the value of the hamstring-to-quadriceps (H/Q) ratio with
      an increase in angular velocity may effectively prevent injuries of the back of
      the thigh. Previous studies have found that the conventional H/Q ratio was
      unaltered along with an increasing angular velocity in females. Therefore, this
      study aimed to investigate the relationships between the conventional H/Q ratio
      and angular velocity in a group of female soccer players. METHODS: The study was
      carried out on a group of 16 female soccer players (age: 20.7 +/- 3.9 years, body
      height: 166.1 +/- 5.8 cm, body mass: 58.4 +/- 6.2 kg, training experience: 8.8 +/
      4.1 years). Measurements of peak torque of extensors and flexors of the knee
      joint under static conditions and under isokinetic conditions (at angular
      velocities of 30 degrees /s, 60 degrees /s, 90 degrees /s and 120 degrees /s)
      were carried out using a Biodex dynamometer. RESULTS: There was a statistically
      significant increase in the conventional H/Q ratio with an increase in angular
      velocity. These differences occurred between measurements at angular velocities
      of 0 degrees /s and 30 degrees /s, and 30 degrees /s and 60 degrees /s.
      CONCLUSIONS: As previously found for males, an increase in conventional H/Q ratio
      with increased angular velocity was also present in this group of female players.
      This phenomenon should reduce the number of injuries of the muscles of back of
      the thigh. Coaches should pay attention to increasing the level of strength in
      the group of knee joint flexor muscles so as to make the value of the H/Q ratio
      appropriately high and increasing with increasing angular velocity.

PMID- 29658522
TI  - Effects of anthropometric factors on postural stability in individuals with
      hearing impairment.
AB  - PURPOSE: Identification of factors that affect postural stability may help to
      improve diagnostic accuracy and enhance the quality of treatment and
      rehabilitation. This study sought to assess the relationship between postural
      stability parameters and anthropometric factors of persons with hearing
      impairment (HI). METHODS: The study included 128 individuals - 42 subjects with
      HI and 86 without HI (healthy controls). Research methodology included an
      interview and a medical examination, anthropometric measurements and
      stabilometric tests on platforms with stable and unstable surfaces. RESULTS: In
      the group of female study participants with HI, significant correlations were
      only noted between body height and the Fall Risk Index (FRI). In the group of
      male subjects with HI, the study revealed significant correlations between FRI
      and body mass, BMI, % MM (muscle mass percentage) and % FAT (fat percentage).
      Moreover, moderate correlation was found between COP path with eyes open and body
      mass, while high correlation was observed between COP path with eyes open and
      BMI, % MM and % FAT. No significant correlation was noted between FRI and body
      height in men with HI. CONCLUSIONS: The examination of correlations between
      postural stability and body build of persons with HI did not confirm the effects
      of body height on postural stability in the examined group of individuals with
      HI, but revealed a greater influence of somatic parameters (body mass, BMI, % MM,
      % FAT) on postural stability in hearing-impaired men.

PMID- 29658523
TI  - Determination of electrophysical and structural properties of human cancellous
      bone and synthetic bone substitute material using impedance spectroscopy and X
      ray powder diffraction.
AB  - Electrophysical stimulation is used to support fracture healing and bone
      regeneration. For design optimization of electrostimulative implants, in
      combination with applied human donor bone or synthetic bone scaffolds, the
      knowledge of electrophysical properties is fundamental. Hence further
      investigations of the structural properties of native and synthetic bone is of
      high interest to improve biofunctionality of bone scaffolds and subsequent
      healing of the bone defect. The investigation of these properties was taken as an
      objective of this study. Therefore, surgically extracted fresh cylindrical and
      consecutively ashed cancellous bone samples from human osteoarthritic femoral
      heads were characterized and compared to synthetic bone substitute material.
      Thereby, impedance spectroscopy is used to determine the electrophysical
      properties and X-ray powder diffraction (XRD) for analysis of structural
      information of the bone samples. Conductivity and permittivity of fresh and ashed
      cancellous bone amounted to 1.7?10-2 S/m and 7.5?106 and 2?10-5 S/m and 7.2?103,
      respectively. Electrical conductivity and dielectric permittivity of bone
      scaffold resulted in 1.7?10-7 S/m and 49. Analysis of the structural properties
      showed that the synthetic bone scaffolds made of Brushite exhibited some
      reflections which correspond to the native bone samples. The information in
      present study of the bone material (synthetic and autologous) could be used for
      later patient individual application of electrostimulative implants.

PMID- 29658524
TI  - Reference values of spatiotemporal parameters, joint angles, ground reaction
      forces, and plantar pressure distribution during normal gait in young women.
AB  - PURPOSE: The aim of this study was to establish the reference values of
      spatiotemporal parameters, joint angles, ground reaction forces and plantar
      pressure distribution collected simultaneously on the same measurement path
      during normal gait in a homogenous group of young, healthy women. METHODS: The
      studied group consisted of 28 healthy women aged 21 years on average. The motion
      capture system BTS Smart-D, 2 AMTI force platforms and Footscan pedobarographic
      platform were used in this research. The 14-metre measurement path and the 6
      metre distance that examined women had to walk through before entering the
      measurement area ensured that a natural gait pattern was recorded. Statistical
      analysis was performed to evaluate differences between right and left lower
      extremities. RESULTS: The applied method enabled collecting several parameters
      regarding normal female gait biomechanics such as: spatiotemporal parameters,
      angle-time characteristics as well as range of motion of pelvis, hip, knee and
      ankle joints in gait cycle, force-time characteristics and peaks of ground
      reaction force components in stance phase, peak pressure and time of loading of
      defined foot regions in stance phase. CONCLUSIONS: The results may be used by
      clinicians, physiotherapists or researchers as a reference in diagnosing gait
      disorders or evaluating patient's walking pattern. In recent literature there are
      some disparities in gait parameters reference values even regarding similar
      research groups. These differences may arise from distinct method, slower or
      faster gait, other laboratory environment etc. This should be considered and more
      than one source of normative values should be checked when searching for
      reference data.

PMID- 29658525
TI  - Countermovement depth - a variable which clarifies the relationship between the
      maximum power output and height of a vertical jump.
AB  - PURPOSE: The aim of this study was to identify the determinants of peak power
      achieved during vertical jumps in order to clarify relationship between the
      height of jump and the ability to exert maximum power. METHODS: One hundred young
      (16.8+/-1.8 years) sportsmen participated in the study (body height 1.861 +/-
      0.109 m, body weight 80.3 +/- 9.2 kg). Each participant performed three jump
      tests: countermovement jump (CMJ), akimbo countermovement jump (ACMJ), and spike
      jump (SPJ). A force plate was used to measure ground reaction force and to
      determine peak power output. The following explanatory variables were included in
      the model: jump height, body mass, and the lowering of the centre of mass before
      launch (countermovement depth). A model was created using multiple regression
      analysis and allometric scaling. RESULTS: The model was used to calculate the
      expected power value for each participant, which correlated strongly with real
      values. The value of the coefficient of determination R2 equalled 0.89, 0.90 and
      0.98, respectively, for the CMJ, ACMJ, and SPJ jumps. The countermovement depth
      proved to be a variable strongly affecting the maximum power of jump. If the
      countermovement depth remains constant, the relative peak power is a simple
      function of jump height. CONCLUSIONS: The results suggest that the jump height of
      an individual is an exact indicator of their ability to produce maximum power.
      The presented model has a potential to be utilized under field condition for
      estimating the maximum power output of vertical jumps.

PMID- 29658526
TI  - Curve fitting problem: torque - velocity relationship with polynomials and
      Boltzmann sigmoid functions.
AB  - PURPOSE: The aim of this study was to investigate the curve fitting and model
      selection problem of the torque-velocity relationship of elbow flexors and
      extensors in untrained females. The second goal was to determine the optimal
      models in different function classes and the best, among the optimal ones.
      Lastly, test the best models to predict the torque were tested. METHODS: Using
      the polynomials (second - fourth degree) and Boltzmann sigmoid functions, and a
      different presentation of data points (averages, a point cloud, etc.), we
      determined the optimal models by both error criteria: minimum residual sum of
      squares and minimum of the maximal absolute residue. To assess the best models,
      we applied Akaike and Bayesian information criteria, Hausdorff distance and the
      minimum of the smallest maximal absolute residue and the predictive torque
      velocity relationships of the best models with torque values, calculated beyond
      the experimental velocity interval. RESULTS: The application of different error
      and model selection criteria showed that the best models in the majority of cases
      were polynomials of fourth degree, with some exceptions from second and third
      degree. The criteria values for the optimal Boltzmann sigmoids were very close to
      those of the best polynomial models. However, the predicted torque-velocity
      relationships had physiological behavior only in Boltzmann's sigmoid functions,
      and their parameters had a clear interpretation. CONCLUSION: The results obtained
      suggest that the Boltzmann sigmoid functions are suitable for modeling and
      predicting of the torque-velocity relationship of elbow flexors and extensors in
      untrained females, as compared to polynomials, and their curves are
      physiologically relevant.

PMID- 29658527
TI  - The differences between overground and treadmill walking in nonlinear, entropy
      based and frequency variables derived from accelerometers in young and older
      women - preliminary report.
AB  - PURPOSE: The aim of this study was to compare gait stability and variability
      between walking conditions and age groups. METHODS: Twenty-six healthy younger
      and older females participated. Trunk acceleration in the vertical (V), medial
      lateral (ML) and anteriorposterior (AP) directions during 5 minutes walking
      overground and 3 minutes walking on the treadmill at self-selected speed were
      recorded. Root mean square and standard deviations of acceleration, stride time
      and its variability, Lyapunov exponents (LE), multiscale entropy (MSE) and
      harmonic ratios (HR) were computed. RESULTS: Both age groups showed significantly
      higher stride time variability and short-term LE in all directions during
      overground walking. For the older group, overground walking showed higher V and
      AP standard deviation. Significantly lower values for overground walking were
      observed for long-term LE (V and ML for the younger group, ML for the older
      group), HR (ML for the older group) and MSE (V for the older group). Significant
      age-related differences were found for V long-term LE for overground walking.
      CONCLUSIONS: The present findings suggest that both linear and advanced
      computational techniques for gait stability and variability assessment in older
      adults are sensitive to walking conditions.

PMID- 29658528
TI  - Gait changes in patients after reconstruction of facial bones with fibula and
      iliac crest free vascularized flaps.
AB  - PURPOSE: Patients with malignant tumours of the oral cavity require its surgical
      removal and reconstruction of the bone and soft tissues. The grafts are obtained
      either from leg (fibula) or pelvis (iliac crest). The removal of grafts from the
      locomotor apparatus can impair the gait. The aim of this study was to find out
      how the localization of donor site influences the gait pattern. METHODS: Results
      obtained for 30 patients were analyzed (16 fibula graft, 14 iliac crest graft).
      Patients underwent instrumented gait analyses three times (VICON system): before
      surgery, 2-4 month after the surgery, and 4-8 months after the surgery. RESULTS:
      In both groups several gait parameters were changed. Two parameters changed in
      both groups: gait speed and cadence. In patients receiving iliac crest graft the
      changed gait variables were: pelvic rotation, hip range in sagittal plane
      (operated side), knee range in sagittal plane (operated side), foot dorsiflexion
      in swing on both sides. In patients receiving fibula flap the changed gait
      variables were: tilt, range motion of the tilt, minimum hip flexion (operated
      side), time to maximum knee flexion (non-operated side), GGI (non-operated side)
      and step length (nonoperated side). CONCLUSIONS: The primary gait deviations
      occurring after surgery, and the compensatory mechanisms which subsequently arise
      depend on the localization of graft donor site. The results indicate that the
      patients in whom fibula flap was used have less problems with gait pattern after
      the surgery than the patients receiving iliac crest graft.

PMID- 29658529
TI  - The effect of trabecular bone storage method on its elastic properties.
AB  - PURPOSE: The purpose of the study was to evaluate the effects of different
      methods of trabecular bone storage on changes in its elastic properties. METHODS:
      186 porcine trabecular bone samples were divided into 6 groups, approximately 30
      samples each. Five groups were stored using the following methods: in buffered
      10% formalin solution at room temperature, frozen at -21 ?C, in the open air at
      room temperature, in 96% alcohol solution and in 50% alcohol solution at room
      temperature. The samples were subjected to compression test to measure the
      elastic modulus. The samples after the first measurement were subjected to
      further measurements for 14 weeks, every 2 weeks. The sixth group was used to
      determine the effects of 10 freeze-thaw cycles on changes in the elastic modulus.
      A Kolmogorov-Smirnov test at significance level p = 0.05 was used to determine
      the significance of changes in time. RESULTS: The changes in elastic properties
      caused by the different storage methods were statistically insignificant, except
      for the group of samples stored in the open air. The changes in elastic modulus
      after 10 freeze-thaw cycles were also statistically insignificant. CONCLUSIONS:
      Except for the storage method in the open air, other storage methods did not
      significantly affect changes in elastic properties of the trabecular bones after
      14 weeks. No effects of 10 freeze-thaw cycles on changes in elastic modulus were
      observed.

PMID- 29658530
TI  - The comparative study of influence of lactic and glycolic acids copolymers type
      on properties of daunorubicin loaded nanoparticles and drug release.
AB  - PURPOSE: The aim of this study was to compare the physico-chemical and biological
      properties of polymeric nanoparticles obtained from poly(DL-lactide-co-glycolide)
      (PLGA) with different ratios of monomers loaded with daunorubicin (DNR). METHODS:
      DNR-loaded nanoparticles (NPs) were prepared with use of modified simultaneous
      double-emulsion solvent evaporation/diffusion technique. NPs were characterized
      using dynamic light scattering, atomic force microscopy, transmission electron
      microscopy, scanning electron microscopy, and differential scanning calorimetry
      and Fourier transform infrared spectroscopy. RESULTS: NPs with DNR were differing
      in size and zeta potential, depending on the type of polymer. The data obtained
      show that total content of DNR correlates with the values of the binding constant
      of DNR with polymers. The release of DNR from NPs proceeds predominantly for
      polymers with lower binding constants. The in vitro study of NPs on the MCF-7
      cells showed similar activity of particles and substances while for the
      anthracycline-resistant MCF-7Adr cells the cytotoxicity of the nanoparticles was
      3 to 7 times higher depending on the type of copolymer. CONCLUSIONS: PLGA DNR
      loaded nanoparticles can be used to overcome multidrug resistance (MDR) as well
      as for reducing the frequency of DNR reception due to the prolonged effect, which
      allows maintaining the concentration of the drug at the required level. The
      usefulness of binding constant calculations for obtaining nanoparticles with the
      maximum drug loading was proven. The rate of drug administration and the
      frequency of administration can be calculated based on the DNR release profiles
      and release parameters that depend on polymer type.

PMID- 29658531
TI  - Preliminary assessment of vibration impacts generated by the public transport
      systems on pregnant women based on subjective reactions.
AB  - PURPOSE: Research efforts summarised in this study were a part of preliminary
      investigation to evaluate the impact of pregnant women's exposure to vibrations
      generated by public transport system when using. METHODS: The assessment of the
      problem and discomfort for pregnant women, caused by the public transportation is
      based on a questionnaire including questions relating to the women's subjective
      feelings on well-being or discomfort when exposed to vibration during the ride in
      passenger cars or when using means of public transport. In the second stage of
      investigation, vibrations transmitted onto a sitting person during the tram or
      car ride were measured. RESULTS: The survey shows that when travelling on a tram
      the women complained mostly of digestive or neurological disorders, during the
      car ride they suffered most acutely from digestive disorders, sensed enhanced
      foetus movements and reported problems with the osteoarticular system. Amplitude
      frequency characteristics of the investigated vehicle types reveal that vibration
      amplitudes registered during the ride in a motor vehicle are higher than on tram
      (in the analysed frequency range). Furthermore, vibration accelerations in the z
      axis direction registered during the tram ride exceed the vibration discomfort
      threshold, particularly for the 1/3 octave bands 5 and 6.3 Hz. These are
      frequency ranges corresponding to resonance frequencies of vital organs in the
      abdominal cavity (4.5-10 Hz). CONCLUSIONS: Correlating these results with
      frequencies reported in literature associated with subjective human responses to
      vibration, shows that pregnant women using public transport are likely to suffer
      from a variety of ailments caused by vibrations generated during the ride.

PMID- 29658532
TI  - Changes of albumin secondary structure after palmitic acid binding. FT-IR
      spectroscopic study.
AB  - PURPOSE: Albumin is an universal transport protein. Plasma pool of free fatty
      acids arising from triglyceride hydrolysis, critical in energy metabolism and
      etiology of metabolic disorders is transported by albumin. According to various
      studies albumin has from seven to nine binding sites with diverse affinity to
      long chain fatty acids. X-ray diffraction crystallography measurements have
      provided data only for pure human serum albumin or albumin with fully saturated
      binding sites. These results have shown that amount of ?-helices is higher after
      fatty acids binding. Molecular mechanics simulations suggest that binding of
      fatty acids in two high-affinity sites leads to major conformational changes in
      albumin structure. The aim of this research was to investigate albumin secondary
      structure upon gradually increasing fatty acids to protein mole ratio. METHODS:
      Fourier transform infrared spectroscopy was applied to study changes of bovine
      serum albumin (as an analogue of human serum albumin) ?-helical structures after
      binding palmitic acid in a range of 0-20 palmitic acid: albumin molar ratios
      representing pure protein, partial, full saturation and excess binding sites
      capacity. RESULTS: Amount of ?-helices was increasing along with the amount of
      palmitic acid: bovine serum albumin molar ratio and reached maximum value around
      2 mol/mol. CONCLUSIONS: Our studies confirmed molecular mechanics simulations and
      crystallographic studies. Palmitic acid binding in two high-affinity sites leads
      to major structural changes, filling another sites only slightly influenced
      bovine serum albumin secondary structure. The systematic study of fatty acids and
      albumin interactions, using an experimental model mimicking metabolic disorders,
      may results in new tools for personalized nanopharmacotherapy.

PMID- 29658533
TI  - Accelerometer profile of motion of the pelvic girdle in butterfly swimming.
AB  - PURPOSE: The aim of the study was to develop a method to measure and analyse
      kinematics of movement of the pelvic girdle in butterfly swimming in order to
      support training of technical skills. METHODS: A device for recording triaxial
      accelerations and triaxial rotational angular velocities was mounted on the
      dorsal part of the pelvic girdle of athlete. The measurements were performed in
      ten elite butterfly swimmers (age: 23.1 +/- 3.7 years, body height: 187.6 +/- 4.3
      cm, body mass 83.4 +/- 6.33 kg). The task of the athlete was to swim one length
      of short course pool at maximal intensity. Individual mean graphical and
      numerical profiles of the kinematics of the movement of the pelvic girdle was
      computed, within the average cycle based on five consecutive cycles. RESULTS:
      Statistical analysis of numerical individual parameters of profiles of the
      athletes studied revealed statistically significant differences between the
      swimmers. Statistically significant correlations were also found between personal
      best times in 50 m swimming (r = -0.76, p < 0.05) and 100 m swimming (r = -0.76,
      p < 0.05) and duration of the part of the cycle connected with the decline in
      velocity from maximum translational motion velocity obtained during propulsion
      with the upper and lower limbs to minimum value of the velocity obtained before
      the beginning of propulsion only with the lower limbs. CONCLUSION: The proposed
      measurement method, presentation and analysis of the profile of the pelvic girdle
      motion in butterfly swimming represents a good tool for fast and effective
      qualitative and quantitative biomechanical evaluation of movement technique
      components.

PMID- 29658535
TI  - [Priorities for the future for a year celebrations of the past].

PMID- 29658534
TI  - The influence of osteoporotic bone structures of the pelvic-hip complex on stress
      distribution under impact load.
AB  - PURPOSE: The aim of this study was to determine the effect of bone mineral
      density (BMD) on the stress distribution in pelvic-hip complex (PHC) model which
      included bone structures and soft tissues. Bone mass changes in osteoporosis and
      osteopenia were considered in this analysis. In addition, the relations between
      force direction and stress distribution causing PHC fractures were determined.
      METHODS: This paper presents the development and validation of a detailed 3D
      finite element model with high anatomical fidelity of the PHC and BMD changes in
      trabecular and cortical bones, modelled based on CT scans. 10 kN loading was
      induced on a model consisting of 8 ligaments, the pelvis, sacrum, femur in front
      and side directions. RESULTS: For validation, the results of this model were
      compared to physiological stress in standing position and previous results with
      high-energy crashes under side impact load. Analysis of side-impact indicated the
      influence of BMD on femoral neck fractures, acetabular cartilage and sacroiliac
      joint delaminations. Front-impact analysis revealed the inferior pubic ramus,
      femoral neck fractures and soft tissue injuries, i.e., acetabular cartilage and
      symphysis pubis in osteoporosis and osteopenia. CONCLUSIONS: The elaborated PHC
      model enables effective prediction of pelvis injuries in high-energy trauma,
      according to Young-Burgess classification, and the determination of the influence
      of BMD reduction on pelvis trauma depending on force direction. The correlation
      between BMD and stress distribution causing varying injuries was determined.

PMID- 29658536
TI  - [Education, motivations and working conditions of a cohort of nurses attending to
      an open-competition].
AB  - : . Education, motivations and working conditions of a cohort of nurses attending
      to an open-competition. INTRODUCTION: In the last decade, the progressive
      reduction of staff turnover decreased together with the number of open
      competitions, now attended by thousands of candidates, portraying an image of
      massive unemployment in the nursing profession. AIM: To describe the socio
      demographic profile, the studies, previous work experiences and motivations of a
      cohort of nurses participats a maxi-competition in Lombardy region. METHODS: A
      questionnaire with 38 questions was administered to collect the socio-demographic
      data, information on education and work activities, their experiences and skills
      and the motivations for participating to the competition. RESULTS: The 6365
      candidates were mainly women; unmarried and young people (mean age 26 years),
      with a degree in nursing obtained mainly in three years (44%). Over all 80% of
      respondents started to work within 1 year post-graduation; 57% were participating
      for the first time to a competition; 27% of candidates were currently employed on
      a temporary or permanent basis. Nurses would like to work in specialty areas such
      as critical care units, emergency departments and operating rooms, although their
      practical training was mainly in medicines and general surgeries. CONCLUSIONS:
      Most nurses are employed few months after graduation. The massive participation
      to public competitions depends on the limited number of procedures and not on the
      excess of nurses. A public competition with thousands of candidates, does not
      allow to select the most competent nurses and should be reformed.

PMID- 29658537
TI  - [Missed nursing care terminologies, theoretical concepts and measurement
      instruments: a literature review].
AB  - : . Missed nursing care terminologies, theoretical concepts and measurement
      instruments: a literature review. INTRODUCTION: In the last 15 years the amount
      of studies on missed nursing care has increased, highlighting the global
      dimensions of this phenomenon. OBJECTIVE: To identify (a) the terms and the
      conceptual models currently available; (b) the measurement tools validated in the
      field of missed care both at the international and at the national levels.
      METHOD: In December 2017 a literature search was conducted by accessing Cochrane
      Library, MEDLINE, CINAHL, Scopus and Web of Science databases. The search
      provided 819 results; after removing duplicates, 273 abstracts were evaluated and
      33 studies included. RESULTS: In the field of missed care, three main approaches
      have been developed to date: (a) Tasks Undone (TU), (b) Implicit Rationing (IR)
      and (c) Missed Nursing Care (MC). Each of these approaches has used different
      definitions, conceptual frameworks and measurement tools and has originated in
      different contexts. Those studies conducted in Italy have been performed mostly
      within the MC approach, by adopting the same definition, conceptual framework and
      instrument. CONCLUSIONS: Overall the missed nursing care definition, its
      conceptual model and the MISSCARE survey tool reflect the most widespread
      approach in the field, both at the international and Italian levels. There is a
      need to develop a common theoretical approach, definition and tool aimed at
      increasing the consistency of evaluations as well as the opportunity of
      international comparisons.

PMID- 29658538
TI  - [Effectiveness of oral nutritional supplements to prevent hospital malnutrition.
      Overview of systematic reviews].
AB  - : . Effectiveness of oral nutritional supplements to prevent hospital
      malnutrition. Overview of systematic reviews. INTRODUCTION: Although oral
      nutritional supplements (ONSs) are among most popular interventions to prevent a
      condition of hospital malnutrition, their real benefits need to be clarified.
      AIM: To evaluate in adults the effectiveness of ONSs to prevent hospital
      malnutrition. METHODS: Papers retrieval by querying biomedical databases The
      Cochrane Library, Medline, Embase, CINAHL. Overview of systematic reviews
      evaluated for methodological quality according to R-AMSTAR checklist with
      narrative synthesis of results. RESULTS: Twenty-five systematic reviews met the
      inclusion criteria. Methodological quality was better in more recent studies. Low
      moderate quality evidence showed a trend for decreasing mortality, complications,
      length of stay; there was no clear reduction in readmissions. Inadequate data do
      not allow to assess the impact on quality of life. The intervention seems
      promising for subjects over 75 years, malnourished, with pathological conditions
      of geriatric interest, in hospital or long-term care services, but differences
      are not always significant. The definition of malnutrition, screening procedures
      and assessment tools adopted varies widely, as well as the characteristics of
      participants, intervention and duration of studies included in systematic
      reviews; this makes difficult to estimate the net benefit due to ONSs.
      CONCLUSIONS: The intervention should be included in a general approach to
      nutrition in clinical practice. At present the role of ONSs to prevent hospital
      malnutrition is still unclear.

PMID- 29658539
TI  - [The voice of nurses on cuts and restructurations of National Health Systems].
AB  - . The recent global economic recession has affected nursing working conditions in
      terms of salary reductions, increased workload and staff shortages. Poor nursing
      working conditions are associated with higher levels of burnout. A literature
      review was conducted to identify contributions of European nurses from 2010 on
      the consequences of the economic crisis on the health services. Only few
      contributions were identified and from a limited number of countries (UK, Italy,
      Spain and Greece).

PMID- 29658541
TI  - [Nurses and drugs. A new journal: Competence 4].

PMID- 29658540
TI  - [About meta-analyses].
AB  - . Based on the publication in this issue of AI&R of a metanalytic assessment of
      the degree and the quality of the available evidences on the clinical efficacy of
      an otherwise diffuse utilization of nutritional integration on a spectrum of
      fragile patients, the methodological comment is focused on the limitations,
      biases, misleading implications which are today threatening the role of
      metanalytical analyses of existing literature, to produce useful-reliable
      evidences in areas where the representativeness of the source of data is
      substantially scarce. The exposure to such risk appears to be specifically
      worrying in the field of nursing care, due to the very limited availability of
      randomized and other "controlled" prospective original studies with hard end
      points.

PMID- 29658542
TI  - [Precision medicine and omic sciences: promises and facts].
AB  - . Precision Medicine refers to the tailoring of medical treatment to the
      individual characteristics of each patient. It aims at classifying individuals
      into subpopulations that differ in their susceptibility to a disease, in the
      biology or prognosis, or in their response to a specific treatment. In this paper
      a general overview of precision medicine is offered, focusing on promises and
      limitations, and stressing its importance also for the nursing profession.

PMID- 29658543
TI  - Rosamine with pyronine-pyridinium skeleton: unique mitochondrial targetable
      structure for fluorescent probes.
AB  - Two rosamine-based probes (1a-b) with pyronine-pyridinium skeleton were designed
      and prepared. Probe 1a bearing boron ester unit was oxidized and eliminated upon
      addition of hydrogen peroxide (H2O2), and the emission spectrum exhibited OFF-ON
      response accompanied by 33-fold fluorescent enhancement. In contrast, the
      fluorescence intensity of probe 1b enhanced 58 times after the dinitrophenyl
      ether part within the probe was removed by nucleophilic substitution with
      hydrosulfide (H2S). The design concept was based on the d-PET process in pyronine
      pyridinium structures, and free 4-pyridinyl-substituted pyronine dye showing
      strong fluorescence was released followed by elimination. Furthermore, as
      biocompatible molecules, probes 1a-b have been successfully applied for imaging
      in live HeLa and Ges-1 cells, and all of them can serve as mitochondrial
      targetable probes in red channel for detecting independent species.

PMID- 29658544
TI  - Aerosol processing: a wind of innovation in the field of advanced heterogeneous
      catalysts.
AB  - Aerosol processing is long known and implemented industrially to obtain various
      types of divided materials and nanomaterials. The atomisation of a liquid
      solution or suspension produces a mist of aerosol droplets which can then be
      transformed via a diversity of processes including spray-drying, spray pyrolysis,
      flame spray pyrolysis, thermal decomposition, micronisation, gas atomisation,
      etc. The attractive technical features of these aerosol processes make them
      highly interesting for the continuous, large scale, and tailored production of
      heterogeneous catalysts. Indeed, during aerosol processing, each liquid droplet
      undergoes well-controlled physical and chemical transformations, allowing for
      example to dry and aggregate pre-existing solid particles or to synthesise new
      micro- or nanoparticles from mixtures of molecular or colloidal precursors. In
      the last two decades, more advanced reactive aerosol processes have emerged as
      innovative means to synthesise tailored-made nanomaterials with tunable surface
      properties, textures, compositions, etc. In particular, the "aerosol-assisted sol
      gel" process (AASG) has demonstrated tremendous potential for the preparation of
      high-performance heterogeneous catalysts. The method is mainly based on the low
      cost, scalable, and environmentally benign sol-gel chemistry process, often
      coupled with the evaporation-induced self-assembly (EISA) concept. It allows
      producing micronic or submicronic, inorganic or hybrid organic-inorganic
      particles bearing tuneable and calibrated porous structures at different scales.
      In addition, pre-formed nanoparticles can be easily incorporated or formed in a
      "one-pot" bottom-up approach within the porous inorganic or hybrid spheres
      produced by such spray drying method. Thus, multifunctional catalysts with
      tailored catalytic activities can be prepared in a relatively simple way. This
      account is an overview of aerosol processed heterogeneous catalysts which
      demonstrated interesting performance in various relevant chemical reactions like
      isomerisation, hydrogenation, olefin metathesis, pollutant total oxidation,
      selective oxidation, CO2 methanation, etc. A short survey of patents and
      industrial applications is also presented. Our objective is to demonstrate the
      tremendous possibilities offered by the coupling between bottom up synthesis
      routes and these aerosol processing technologies which will most probably
      represent a major route of innovation in the mushrooming field of catalyst
      preparation research.

PMID- 29658545
TI  - Current characterization methods for cellulose nanomaterials.
AB  - A new family of materials comprised of cellulose, cellulose nanomaterials (CNMs),
      having properties and functionalities distinct from molecular cellulose and wood
      pulp, is being developed for applications that were once thought impossible for
      cellulosic materials. Commercialization, paralleled by research in this field, is
      fueled by the unique combination of characteristics, such as high on-axis
      stiffness, sustainability, scalability, and mechanical reinforcement of a wide
      variety of materials, leading to their utility across a broad spectrum of high
      performance material applications. However, with this exponential growth in
      interest/activity, the development of measurement protocols necessary for
      consistent, reliable and accurate materials characterization has been outpaced.
      These protocols, developed in the broader research community, are critical for
      the advancement in understanding, process optimization, and utilization of CNMs
      in materials development. This review establishes detailed best practices,
      methods and techniques for characterizing CNM particle morphology, surface
      chemistry, surface charge, purity, crystallinity, rheological properties,
      mechanical properties, and toxicity for two distinct forms of CNMs: cellulose
      nanocrystals and cellulose nanofibrils.

PMID- 29658546
TI  - Influence of molecular weight between crosslinks on the mechanical properties of
      polymers formed via ring-opening metathesis.
AB  - The apparent molecular weight between crosslinks (Mc,a) in a polymer network
      plays a fundamental role in the network mechanical response. We systematically
      varied Mc,a independent of strong noncovalent bonding by using ring-opening
      metathesis polymerization (ROMP) to co-polymerize dicyclopentadiene (DCPD) with a
      chain extender that increases Mc,a or a di-functional crosslinker that decreases
      Mc,a. We compared the ROMP series quasi-static modulus (E), tensile yield stress
      (sigmay), and fracture toughness (KIC and GIC) in the glassy regime with
      literature data for more polar thermosets. ROMP resins showed high KIC (>1.5 MPa
      m0.5), high GIC (>1000 J m-2), and 4-5 times higher high rate impact resistance
      than typical polar thermosets with similar Tg values (100  degrees C to 178 
      degrees C). The overall E values were lower for ROMP systems. The sigmay
      dependence on Mc,a and T-Tg for ROMP resins was qualitatively similar to more
      polar thermosets, but the overall sigmay values were lower. In contrast to more
      polar thermosets, the KIC and GIC values of the ROMP resins showed strong Mc,a
      and T-Tg dependence. High rate impact (~104-105 s-1) trends were similar to the
      KIC and GIC behavior, but were also correlated to sigmay. Overall, a ductile
      failure mode was observed for quasi-static and high rate results for a linear
      ROMP polymer (Mc,a = 1506 g mol-1 due to chain entanglement), and this gradually
      transitioned to a fully brittle failure mode for highly crosslinked ROMP polymers
      (Mc,a <= 270 g mol-1). Molecular dynamics (MD) simulations showed that low Mc,a
      ROMP resins were more likely to form molecular scale nanovoids. The higher chain
      stiffness in low Mc,a ROMP resins inhibited stress relaxation in the vicinity of
      these nanovoids, which correlated with brittle mechanical responses. Overall,
      these differences in mechanical properties were attributed to the weak non
      covalent interactions in ROMP resins.

PMID- 29658547
TI  - A ratiometric iron probe enables investigation of iron distribution within tumour
      spheroids.
AB  - Iron dysregulation is implicated in numerous diseases, and iron homeostasis is
      profoundly influenced by the labile iron pool (LIP). Tools to easily observe
      changes in the LIP are limited, with calcein AM-based assays most widely used. We
      describe here FlCFe1, a ratiometric analogue of calcein AM, which also provides
      the capacity for imaging iron in 3D cell models.

PMID- 29658548
TI  - A solution NMR toolset to probe the molecular mechanisms of amyloid inhibitors.
AB  - The self-association of the amyloid beta (Abeta) peptide into toxic oligomers is
      implicated in the early events leading to Alzheimer's disease (AD). Blocking the
      formation of Abeta oligomers and their interactions with the extracellular and
      cellular environment through small molecules and biopharmaceuticals is therefore
      a promising preventive strategy for AD. However, given the heterogeneity and
      transient nature of the Abeta oligomeric species, detailed structural and kinetic
      characterizations of such oligomers and oligomer:inhibitor complexes have proven
      to be challenging. Here, we discuss recent advancements in solution NMR that have
      been instrumental in overcoming these limitations and we provide two
      representative examples of Abeta inhibitors from our work to demonstrate the
      applications of such experiments, i.e. EGCG and human serum albumin.

PMID- 29658552
TI  - Exfoliation of ultrathin FePS3 layers as a promising electrocatalyst for the
      oxygen evolution reaction.
AB  - Few-layer ternary FePS3 nanosheets, prepared via chemical vapor transport
      synthesis and ball-milling exfoliation, exhibit excellent electrocatalytic
      performance for the oxygen evolution reaction in an alkaline medium. Combined
      with first principles calculations, our X-ray spectroscopy and HRTEM results
      clearly reveal that the introduction of in-plane defects in FePS3 layers after
      exfoliation and formation of a FePS3-FeOOH heterostructure during the OER process
      largely contribute to the catalytic activity enhancement.

PMID- 29658553
TI  - Protein-protein interactions within photosystem II under photoprotection: the
      synergy between CP29 minor antenna, subunit S (PsbS) and zeaxanthin at all-atom
      resolution.
AB  - The assembly and disassembly of protein complexes within cells are crucial life
      sustaining processes. In photosystem II (PSII) of higher plants, there is a
      delicate yet obscure balance between light harvesting and photo-protection under
      fluctuating light conditions, that involves protein-protein complexes. Recent
      breakthroughs in molecular dynamics (MD) simulations are combined with new
      approaches herein to provide structural and energetic insight into such a complex
      between the CP29 minor antenna and the PSII subunit S (PsbS). The microscopic
      model involves extensive sampling of bound and dissociated states at atomic
      resolution in the presence of photo-protective zeaxanthin (Zea), and reveals well
      defined protein-protein cross-sections. The complex is placed within PSII, and
      macroscopic connections are emerging (PsbS-CP29-CP24-CP47) along the energy
      transfer pathways from the antenna to the PSII core. These connections explain
      macroscopic observations in the literature, while the previously obscured atomic
      scale details are now revealed. The implications of these findings are discussed
      in the context of the Non-Photochemical Quenching (NPQ) of chlorophyll
      fluorescence, the down-regulatory mechanism of photosynthesis, that enables the
      protection of PSII against excess excitation load. Zea is found at the PsbS-CP29
      cross-section and a pH-dependent equilibrium between PsbS dimer/monomers and the
      PsbS-CP29 dissociation/association is identified as the target for engineering
      tolerant plants with increased crop and biomass yields. Finally, the new MD based
      approaches can be used to probe protein-protein interactions in general, and the
      PSII structure provided can initiate large scale molecular simulations of the
      photosynthetic apparatus, under NPQ conditions.

PMID- 29658554
TI  - A sinter-resistant catalyst using an alumina support recycled from AlP fumigation
      residue: trash to treasure.
AB  - Sintering is a long-standing issue especially in high temperature catalytic
      applications. In this paper, we report an effective method to slow down metal
      particle migration and coalescence (PMC) by using a thermally stable alumina
      support. Noteworthily, the alumina sample was developed from AlP fumigation
      residue, which is a very dangerous substance for living creatures and environment
      protection. By optimizing the heated hydrolysis and ball-milling conditions, we
      recycled a phosphate-stabilized alumina material that retained a 117 m2 g-1
      surface area after 1050  degrees C hydrothermal aging. The catalyst using this
      newly developed alumina support had Pd dispersion 1.7 times higher than that
      using a commercial alumina support after aging. The kinetics and XPS experiments
      showed that phosphate neither participated in the catalytic reaction process nor
      changed the active sites. This catalyst also exhibited extraordinary water
      tolerance and durability, making it a promising material in automotive exhaust
      purification and other catalytic applications.

PMID- 29658556
TI  - Thermodynamic versus non-equilibrium stability of palmitic acid monolayers in
      calcium-enriched sea spray aerosol proxy systems.
AB  - Of the major cations in seawater (Na+, Mg2+, Ca2+, K+), Ca2+ is found to be the
      most enriched in fine sea spray aerosols (SSA). In this work, we investigate the
      binding of Ca2+ to the carboxylic acid headgroup of palmitic acid (PA), a marine
      abundant fatty acid, and the impact such binding has on the stability of PA
      monolayers in both equilibrium and non-equilibrium systems. A range of Ca2+
      conditions from 10 MUM to 300 mM was utilized to represent the relative
      concentration of Ca2+ in high and low relative humidity aerosol environments. The
      CO2- stretching modes of PA detected by surface-sensitive infrared reflection
      absorption spectroscopy (IRRAS) reveal ionic binding motifs of the Ca2+ ion to
      the carboxylate group with varying degrees of hydration. Surface tensiometry was
      used to determine the thermodynamic equilibrium spreading pressure (ESP) of PA on
      the various aqueous CaCl2 subphases. Up to concentrations of 1 mM Ca2+, each
      system reached equilibrium, and Ca2+:PA surface complexation gave rise to a lower
      energy state revealed by elevated surface pressures relative to water. We show
      that PA films are not thermodynamically stable at marine aerosol-relevant Ca2+
      concentrations ([Ca2+] >= 10 mM). IRRAS and vibrational sum frequency generation
      (VSFG) spectroscopy were used to investigate the surface presence of PA on high
      concentration Ca2+ aqueous subphases. Non-equilibrium relaxation (NER)
      experiments were also conducted and monitored by Brewster angle microscopy (BAM)
      to determine the effect of the Ca2+ ions on PA stability. At high surface
      pressures, the relaxation mechanisms of PA varied among the systems and were
      dependent on Ca2+ concentration.

PMID- 29658557
TI  - Ab initio quantum transport in polycrystalline graphene.
AB  - Synthesis techniques such as chemical vapor deposition yield graphene in
      polycrystalline flakes where single-crystal domains are separated by grain
      boundaries (GBs) of irregular shape. These structural defects are mostly made up
      of pentagon-heptagon pairs and represent an important source of scattering, thus
      strongly affecting electronic mobilities in polycrystalline graphene (PG). In the
      present article, first-principles simulations are performed to explore charge
      transport through a GB in PG using the Landauer-Buttiker formalism implemented
      within the Green's function approach. In ideal GB configurations, electronic
      transport is found to depend on their topology as already suggested in the
      literature. However, more realistic GBs constructed out of various carbon rings
      and with more complex periodicities are also considered, possibly inducing
      leakage currents. Finally, additional realistic disorder such as vacancies, a
      larger inter-connectivity region and out-of plane buckling is investigated. For
      specific energies, charge redistribution effects related to the detailed GB
      topology are found to substantially alter the transmissions. Altogether, the
      transport gap is predicted to be inversely proportional to the smallest
      significant periodic pattern and nearly independent of the interface
      configuration.

PMID- 29658555
TI  - Membrane-containing virus particles exhibit the mechanics of a composite material
      for genome protection.
AB  - The protection of the viral genome during extracellular transport is an absolute
      requirement for virus survival and replication. In addition to the almost
      universal proteinaceous capsids, certain viruses add a membrane layer that
      encloses their double-stranded (ds) DNA genome within the protein shell. Using
      the membrane-containing enterobacterial virus PRD1 as a prototype, and a
      combination of nanoindentation assays by atomic force microscopy and finite
      element modelling, we show that PRD1 provides a greater stability against
      mechanical stress than that achieved by the majority of dsDNA icosahedral viruses
      that lack a membrane. We propose that the combination of a stiff and brittle
      proteinaceous shell coupled with a soft and compliant membrane vesicle yields a
      tough composite nanomaterial well-suited to protect the viral DNA during
      extracellular transport.

PMID- 29658559
TI  - Modern science of a legacy problem: mercury biogeochemical research after the
      Minamata Convention.

PMID- 29658558
TI  - Nanoencapsulation of phase change materials for advanced thermal energy storage
      systems.
AB  - Phase change materials (PCMs) allow the storage of large amounts of latent heat
      during phase transition. They have the potential to both increase the efficiency
      of renewable energies such as solar power through storage of excess energy, which
      can be used at times of peak demand; and to reduce overall energy demand through
      passive thermal regulation. 198.3 million tons of oil equivalent were used in the
      EU in 2013 for heating. However, bulk PCMs are not suitable for use without prior
      encapsulation. Encapsulation in a shell material provides benefits such as
      protection of the PCM from the external environment and increased specific
      surface area to improve heat transfer. This review highlights techniques for the
      encapsulation of both organic and inorganic PCMs, paying particular attention to
      nanoencapsulation (capsules with sizes <1 MUm). We also provide insight on future
      research, which should focus on (i) the development of multifunctional shell
      materials to improve lifespan and thermal properties and (ii) advanced mass
      manufacturing techniques for the economically viable production of PCM capsules,
      making it possible to utilize waste heat in intelligent passive thermal
      regulation systems, employing controlled, "on demand" energy release/uptake.

PMID- 29658560
TI  - A substituent-tolerant synthetic approach to N/P-"loaded" heteroarenes.
AB  - Tetrazines react with OCP-1 through a reverse electron demand Diels-Alder process
      to produce 3,6-disubstituted-1,2,4-diazaphosphinin-5-olates. DFT calculations
      reveal that both Diels-Alder and subsequent aromatization barriers are low for
      both EWG and ED tetrazine substituents. The structure of the solid sodium salt
      shows the interaction of Na+ with aryloxide and also both nitrogens of a
      neighboring anion, leading to coordination polymer character. 1,2,4
      Diazaphosphinin-5-olates react as nucleophiles towards MeI and R3SiCl,
      respectively, and were installed on the (Ph3P)2Ru(CO)H fragment to investigate
      their properties as ligands.

PMID- 29658561
TI  - Plasma cholesterol lowering in an AngII-infused atherosclerotic mouse model with
      moderate hypercholesterolemia.
AB  - Atherosclerosis is the main underlying causes of cardiovascular disease. There is
      a well-established association between high blood cholesterol levels and the
      extent of atherosclerosis. Furthermore, atherosclerosis has been proposed to
      augment abdominal aortic aneurysm (AAA) formation. As patients with AAA often
      have parallel atherosclerotic disease and are therefore often on cholesterol
      lowering therapy, it is not possible to fully address the independent effects of
      plasma cholesterol lowering (PCL) treatment on AAA. The present study
      investigated the effect of angiotensin II (AngII)-infusion in modestly
      hypercholesterolemic Ldlr-/-Apob100/100Mttpflox/floxMx1-Cre mice with or without
      PCL treatment on a morphological and molecular level, in terms of atherosclerosis
      and AAA development. AngII infusion in the study mice resulted in an increased
      atherosclerotic lesion area and increased infiltration of inflammatory
      leukocytes, which was not observed in mice with PCL induced prior to AngII
      infusion. This suggested that AngII infusion in this mouse model induced
      atherosclerosis development, and that plasma cholesterol levels represent a
      controlling factor. Furthermore, AngII infusion in Ldlr-/
      Apob100/100Mttpflox/floxMx1-Cre mice caused a modest aneurysmal phenotype, and no
      differences in AAA development were observed between the different study groups.
      However, the fact that modest hypercholesterolemic mice did not develop AAA in a
      classical aneurysmal model indicated that plasma cholesterol levels are important
      for disease development.

PMID- 29658562
TI  - MicroRNA-34a mediates atrial fibrillation through regulation of Ankyrin-B
      expression.
AB  - Atrial fibrillation (AF) has a high prevalence and recurrence rate, and is
      associated with substantial mortality. However, its underlying mechanisms are not
      thoroughly understood. Increasing attention has been paid to the roles of
      microRNAs (miRs) in the pathogenesis of cardiovascular disease, including miR-1
      and miR-133 (in the electrophysiological response), and miR-34a (in cardiac
      fibrosis). Recently, Ankyrin-B (Ank-B), an adaptor protein, has been demonstrated
      to be associated with AF. As a predicted target gene of miR-34a, the present
      study aimed to investigate if miR-34a has a role in AF via regulation of Ank-B
      expression. Western blot analysis revealed that the expression levels of Ank-B
      was lower in the atrial tissue of AF patients than in individuals with sinus rate
      (SR); however, reverse transcription-quantitative polymerase chain reaction data
      demonstrated that miR-34a expression exhibited the opposite pattern. Dual
      luciferase assays following the specific overexpression or inhibition of miR-34a
      indicated that the 3' untranslated region of Ankyrin 2 (the gene encoding Ank-B)
      contained binding sites for miR-34a. Furthermore, the expression levels of Ank-B
      and sodium-calcium exchanger 1 (an Ank-B binding partner important in Ca2+
      homeostasis), as well as intracellular Ca2+ signaling detected by Fluoro-3 AM,
      were altered following the modulation of miR-34a expression. Thus, miR-34a may
      serve an important role in early electrophysiological remodeling and the
      development of AF via the regulation of Ank-B expression. These results offer
      valuable insight into the underlying mechanism of AF, and provide a promising
      target for developing clinical diagnostic tools and potential therapies for
      patients with AF.

PMID- 29658563
TI  - Preclinical evaluation of a novel engineered recombinant human anti-CD44v6
      antibody for potential use in radio-immunotherapy.
AB  - CD44v6 is overexpressed in a variety of cancers, rendering it a promising target
      for radio-immunotherapy (RIT). In this study, we have characterized a novel
      engineered recombinant monoclonal anti-CD44v6 antibody, AbN44v6, and assessed its
      potential for use in RIT using either 177Lu or 131I as therapeutic radionuclides.
      In vitro affinity and specificity assays characterized the binding of the
      antibody labeled with 177Lu, 125I or 131I. The therapeutic effects of 177Lu
      AbN44v6 and 131I-AbN44v6 were investigated using two in vitro 3D tumor models
      with different CD44v6 expression. Finally, the normal tissue biodistribution and
      dosimetry for 177Lu-AbN44v6 and 125I-AbN44v6/131I-AbN44v6 were assessed in vivo
      using a mouse model. All AbN44v6 radioconjugates demonstrated CD44v6-specific
      binding in vitro. In the in vitro 3D tumor models, dose-dependent therapeutic
      effects were observed with both 177Lu-AbN44v6 and 131I-AbN44v6, with a greater
      significant therapeutic effect observed on the cells with a higher CD44v6
      expression. Biodistribution experiments demonstrated a greater uptake of 177Lu
      AbN44v6 in the liver, spleen and bone, compared to 125I-AbN44v6, whereas 125I
      AbN44v6 demonstrated a longer circulation time. In dosimetric calculations, the
      critical organs for 177Lu-AbN44v6 were the liver and spleen, whereas the kidneys
      and red marrow were considered the critical organs for 131I-AbN44v6. The
      effective dose was in the order of 0.1 mSv/MBq for both labels. In conclusion,
      AbN44v6 bound specifically and with high affinity to CD44v6. Furthermore, in
      vitro RIT demonstrated growth inhibition in a CD44v6-specific activity-dependent
      manner for both radioconjugates, demonstrating that both 177Lu-AbN44v6 and 131I
      AbN44v6 may be promising RIT candidates. Furthermore, biodistribution and
      dosimetric analysis supported the applicability of both conjugates for RIT. The
      CD44v6-specific therapeutic effects observed with radiolabeled AbN44v6 in the 3D
      tumor models in vitro, combined with the beneficial dosimetry in vivo, render
      AbN44v6 a potential candidate for RIT.

PMID- 29658564
TI  - C-terminal binding protein-2 mediates cisplatin chemoresistance in esophageal
      cancer cells via the inhibition of apoptosis.
AB  - C-terminal binding protein-2 (CtBP2) is a transcriptional co-repressor that is
      associated with tumorigenesis and tumor progression. It has been reported to
      predict a poor prognosis in several human cancers, including esophageal squamous
      cell carcinoma (ESCC). The present study aimed to investigate the involvement of
      CtBP2 in the cisplatin (DDP) resistance of the ECA109 ESCC cell line and its
      effect on the expression of apoptosis-associated proteins. Constructed
      recombinant lentiviruses were used for the knockdown or overexpression of CtBP2
      in ECA109 cells, and the expression of CtBP2 was measured using reverse
      transcription-quantitative polymerase chain reaction and western blotting
      following transfection. MTT assays, Hoechst 33342 staining and flow cytometry
      (FCM) were applied to detect the influence of CtBP2 on the DDP-induced viability
      and apoptosis of the transfected ECA109 cells. In addition, the levels of
      apoptosis-associated proteins, including p53, B-cell lymphoma 2 (Bcl-2), Bcl-2
      associated X protein (Bax) and activated caspase-3 were investigated in the
      transfected ECA109 cells. Stable ECA109 cells with CtBP2 overexpression or
      knockdown were successfully established. The results of the MTT, Hoechst 33342
      and FCM assays demonstrated that overexpression of CtBP2 attenuated the reduction
      of cell viability and inhibited the cell apoptosis induced by DDP. Furthermore,
      the western blotting results indicated that CtBP2 overexpression inhibited the
      DDP-induced apoptosis of ECA109 cells via the reduction of p53, activated caspase
      3 and Bax expression, and promotion of Bcl-2 expression. Therefore, the present
      study indicated that CtBP2 reduced the susceptibility of ECA109 cells to DDP by
      regulating the expression of apoptosis-related proteins, suggesting that it may
      be a promising therapeutic target in ESCC in the future.

PMID- 29658565
TI  - (-)-Epicatechin protects against myocardial ischemia-induced cardiac injury via
      activation of the PTEN/PI3K/AKT pathway.
AB  - Flavonol (-)-epicatechin (EPI) is primarily contained in green tea (Camellia
      sinensis) and cocoa beans (Theobroma cacao), and has been demonstrated to be
      beneficial for the health of the cardiovascular system. However, the effect and
      the underlying mechanism of EPI on myocardial ischemia induced cardiac injury has
      not yet been determined. Therefore, the present study aimed to detect whether EPI
      inhibited myocardial ischemia injury. An in vivo mouse myocardial ischemia model
      was induced by the ligation of left descending coronary artery for 7 days. EPI (1
      mg/kg/day) was administrated 10 days prior to myocardial ischemia operation. The
      in vitro mouse myocardial ischemia model was induced by cultivating neonatal
      mouse cardiomyocytes under anoxia condition for 12 h. Cardiomyocytes were treated
      with EPI (5 uM) for 1 h and then incubated under anoxia conditions. Mouse hearts
      and cultured cardiomyocytes were used for hematoxylin-eosin, masson,
      ultrasonography, terminal dUTP nick end-labeling, immunofluorescence, western
      blotting and MTT assays. Results revealed that myocardial ischemia-induced mouse
      cardiac injury was significantly inhibited by EPI, as evidenced by decreased
      myocardial apoptosis, cardiac fibrosis and myocardial hypertrophy and improved
      cardiac function. In addition, it was confirmed that EPI serves a protective
      effect against myocardial ischemia via the phosphatase and tensin homolog
      (PTEN)/phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway,
      which was reversed by the PI3K inhibitor, LY294002. The protective role of EPI in
      myocardial apoptosis was further confirmed on mouse cardiomyocytes following
      anoxia treatment in vitro. In conclusion, the data suggested that EPI protects
      against myocardial ischemia induced cardiac injury through the PTEN/PI3K/AKT
      signaling pathway in vivo and in vitro, which may provide clinical therapeutic
      approaches and targets for cardiac ischemia injury.

PMID- 29658566
TI  - PEEK-biphasic bioceramic composites promote mandibular defect repair and
      upregulate BMP-2 expression in rabbits.
AB  - The present study aimed to investigate whether bone morphogenetic protein-2 (BMP
      2) was involved in the repair of mandibular defects using polyether-ether-ketone
      biphasic bioceramic (PEEK-BBC) composites in rabbits. PEEK-BBC composites with
      abundant and interconnected pores were prepared by calcination and characterized
      by scanning electron microscope. A mandibular defect model in rabbits was
      established using dental grinder to produce a square hole. A total of 60 rabbits
      were divided into four groups: Control, sham, surgery, and PEEK. In the PEEK
      group, the holes were filled with the PEEK-BBC composite stents. In the surgery
      group, the holes were produced but not filled with the composite stents. In the
      sham group, only the molar grooves were exposed and grinding was not performed.
      Animals without any treatment served as the control group. The success rate of
      model establishment was 100%. At 4, 8, and 16 weeks after the model was
      established, samples were collected from the molding sites. Bone repair was
      evaluated by H&E staining and Goldner trichrome staining. Bone structures in both
      control and sham groups were intact. A small number of osteocytes were observed
      in the surgery group. However, in the PEEK group, osteocytes were already
      evidently present in the composites at 4 weeks after surgery. At 8 and 16 weeks,
      there were large numbers of osteocytes in the pores of the composites. The mRNA
      and protein expression levels of BMP-2 were determined by reverse transcription
      quantitative polymerase chain reaction and western blotting, respectively. The
      mRNA and protein expression levels of BMP-2 between the control and sham groups
      were similar and were continuously stable. However, following defect treatment,
      BMP-2 mRNA and protein expression was upregulated, which was enhanced by the PEEK
      BBC composites. In conclusion, PEEK-BBC composites promoted the growth of
      osteocytes and repaired mandibular defects in rabbits, potentially via the
      upregulation of BMP-2 expression.

PMID- 29658567
TI  - HepaCAM inhibits the malignant behavior of castration-resistant prostate cancer
      cells by downregulating Notch signaling and PF-3084014 (a gamma-secretase
      inhibitor) partly reverses the resistance of refractory prostate cancer to
      docetaxel and enzalutamide in vitro.
AB  - Castration-resistant prostate cancer (CRPC) continues to be a major challenge in
      the treatment of prostate cancer (PCa). The expression of hepatocyte cell
      adhesion molecule (HepaCAM), a novel tumor suppressor, is frequently
      downregulated or lost in PCa. Overactivated Notch signaling is involved in the
      development and progression of PCa, including CRPC. In this study, we found that
      the activities of Notch signaling were elevated, while HepaCAM expression was
      decreased in CRPC tissues compared with matched primary prostate cancer (PPC)
      tissues. In addition, HepaCAM negativity was found to be associated with a worse
      progression-free survival (PFS). Furthermore, the overexpression of HepaCAM
      induced by transfection with a HepaCAM overexpression vector (Ad-HepaCAM) exerted
      antitumor effects by decreasing the proliferation, and suppressing the invasion
      and migration of bicalutamide-resistant (Bica-R) cells and enzalutamide-resistant
      (Enza-R) cells. Importantly, we found that the antitumor effects of HepaCAM on
      the resistant cells were associated with the downregulation of Notch signaling.
      Moreover, we revealed that PF-3084014 (a gamma-secretase inhibitor) re-sensitized
      Enza-R cells to enzalutamide, and sequential dual-resistant (E+D-R) cells to
      docetaxel. Additionally, the findings of this study demonstrated that the use of
      PF-3084014 alone exerted potent antitumor effect on the resistant cells in vitro.
      On the whole, this study indicates that HepaCAM potentially represents a
      therapeutic target and PF-3084014 may prove to a promising agent for use in the
      treatment of refractory PCa.

PMID- 29658568
TI  - Circular RNA circCDK13 suppresses cell proliferation, migration and invasion by
      modulating the JAK/STAT and PI3K/AKT pathways in liver cancer.
AB  - Circular RNAs have recently been disclosed as potential biomarkers for human
      cancers. This study aimed to characterize the expression and function of a novel
      circular RNA, circCDK13, in liver cancer progression, as well as to elucide the
      underlying mechanisms. For this purpose, circCDK13 expression was quantitatively
      analyzed by RT-PCR in various liver cancer cell lines and human cancerous
      tissues. The migration, cell cycle progression, proliferation and invasion of
      liver cancer cells with an enhanced circCDK13 expression were evaluated by 3-(4,5
      dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H
      tetrazolium, inner salt (MTS) assay, flow cytometry and the Transwell culture
      system. Microarray and western blot analyses were performed to explore the
      underlying signaling mechanisms. The role of circCDK13 in liver cancer was
      finally examined by tumorigenicity assay using nude mice. The results revealed
      that circCDK13 expression was suppressed in various liver cancer lines and tissue
      samples from patients with liver cancer (hepatocellular carcinoma). The induced
      overexpression of circCDK13 in the liver cancer cells markedly inhibited their
      migration rates, altered cell cycle progression, and suppressed the cell
      migratory and invasive capacities. Microarray analysis also identified numerous
      downstream genes regulated by circCDK13, particularly those in the Janus tyrosine
      kinase (JAK)/signal transducer and activator of transcription (STAT) and
      phosphoinositide 3-kinase (PI3K)/AKT signaling pathways. The results of the
      tumorigenicity assay revealed that circCDK13 overexpression significantly
      inhibited liver cancer progression in nude mice. On the whole, the findings of
      this study indicate that circCDK13 is a novel circular RNA that suppresses liver
      cancer progression, and that these suppressive effects are possibly mediated via
      the JAK/STAT and PI3K/AKT signaling pathways.

PMID- 29658569
TI  - beta-catenin nuclear translocation induced by HIF-1alpha overexpression leads to
      the radioresistance of prostate cancer.
AB  - Hypoxia-inducible factor-1alpha (HIF-1alpha) is known to play crucial roles in
      tumor radioresistance; however, the molecular mechanisms responsible for the
      promotion of tumor radioresistance by HIF-1alpha remain unclear. beta-catenin is
      known to be involved in the metastatic potential of prostate cancer (PCa). In
      this study, to investigate the role of HIF-1alpha and beta-catenin in the
      radioresistance of PCa, two PCa cell lines, LNCaP and C4-2B, were grouped as
      follows: Negative control (no treatment), HIF-1alpha overexpression group
      (transfected with HIF-1alpha overexpression plasmid) and beta-catenin silenced
      group (transfected with HIF-1alpha plasmids and beta-catenin-shRNA). Cell
      proliferation, cell cycle, cell invasion and radiosensitivity were examined under
      normal or hypoxic conditions. In addition, radiosensitivity was examined in two
      mouse PCa models (the LNCaP orthotopic BALB/c-nu mice model and the C4-2B
      subcutaneous SCID mice model). Our results revealed that in both the LNCaP and C4
      2B cells, transfection with HIF-1alpha overexpression plasmid led to an enhanced
      beta-catenin nuclear translocation, while beta-catenin silencing inhibited beta
      catenin nuclear translocation. The enhanced beta-catenin nuclear translocation
      induced by HIF-1alpha overexpression resulted in an enhanced cell proliferation
      and cell invasion, an altered cell cycle distribution, decreased apoptosis, and
      improved non-homologous end joining (NHEJ) repair under normal and irradiation
      conditions. Similar results were observed in the animal models. HIF-1alpha
      overexpression enhanced beta-catenin nuclear translocation, which led to the
      activation of the beta-catenin/NHEJ signaling pathway and increased cell
      proliferation, cell invasion and DNA repair. These results thus suggest that HIF
      1alpha overexpression promotes the radioresistance of PCa cells.

PMID- 29658570
TI  - JWA suppresses the invasion of human breast carcinoma cells by downregulating the
      expression of CXCR4.
AB  - Breast cancer is the second leading cause of cancer-associated mortality, and
      metastatic breast cancer is responsible for 90% of patient mortalities. Given
      that JWA represses the proliferation, invasion and metastasis of a number of
      other human tumor cells, including melanoma, esophageal, hepatocellular and
      gastric carcinomas, via mitogen-activated protein kinase or integrin signaling,
      the present study investigated the expression and function of JWA in human breast
      cancers. The results showed that the expression level of JWA was significantly
      reduced in human primary breast cancers when compared with the paired adjacent
      tissues. Downregulating JWA enhanced, while overexpressing JWA suppressed, the
      migration and invasion abilities of the two breast cancer cell lines, MDA-MB-468
      and MDA-MB-231, without affecting their proliferations in vitro. In addition, JWA
      negatively regulated the surface expression of CXCR4 in the two cell lines via
      proteasome degradation, though not via transcriptional inhibition. Functionally,
      normalizing the disturbed expressions of CXCR4 largely reversed the inhibitory
      effect of JWA on cell invasion. These data demonstrated that JWA suppressed the
      migration/invasion of breast carcinoma cells by downregulating the expression of
      CXCR4, and suggested that JWA may harbor prognostic and therapeutic potential in
      patients with breast cancer.

PMID- 29658571
TI  - Upregulation of HOXA1 promotes tumorigenesis and development of non-small cell
      lung cancer: A comprehensive investigation based on reverse transcription
      quantitative polymerase chain reaction and bioinformatics analysis.
AB  - Homeobox A1 (HOXA1) serves an oncogenic role in multiple cancer types. However,
      the role of HOXA1 in non-small cell lung cancer (NSCLC) remains unclear. In the
      present study, use of reverse transcription-quantitative polymerase chain
      reaction and the databases of The Cancer Genome Atlas (TCGA), Oncomine, Gene
      Expression Profiling Interactive Analysis and the Multi Experiment Matrix were
      combined to assess the expression of HOXA1 and its co-expressed genes in NSCLC.
      Bioinformatic analyses, such as Gene Ontology (GO), Kyoto Encyclopedia of Genes
      and Genomes (KEGG), and network and protein-protein interaction analyses, were
      used to investigate the underlying molecular mechanism effected by the co
      expressed genes. Additionally, the potential miRNAs targeting HOXA1 were
      investigated. The results showed that HOXA1 was upregulated in NSCLC. The area
      under the curve of HOXA1 indicated a moderate diagnostic value of the HOXA1 level
      in NSCLC. According to GO and KEGG analyses, the co-expressed genes may be
      involved in 'dGTP metabolic processes', 'network-forming collagen trimers',
      'centromeric DNA binding' and 'the p53 signaling pathway'. Three miRNAs (miR-181b
      5p, miR-28-5p and miR-181d-5p) targeting HOXA1 were each predicted by 10
      algorithms; miR-181b and miR-181d levels were downregulated in LUSC tissues
      compared with those in normal lung tissues based on data from the TCGA database,
      and inverse correlations were found between HOXA1 and miR-181b (r=-0.205,
      P<0.001) and miR-181d (r=-0.106, P=0.020). We speculate that HOXA1 may be the
      direct target of miR-181b-5p or miR-181d-5p in LUSC, and HOXA1 may serve a
      significant role in NSCLC by regulating various pathways, particularly the p53
      signaling pathway. However, the detailed mechanism should be verified by
      functional experiments.

PMID- 29658572
TI  - PKR inhibition mediates endotoxin tolerance in macrophages through inactivation
      of PI3K/AKT signaling.
AB  - Following long-term exposure to endotoxins, macrophages enter an
      immunosuppressive state that renders them unable respond to subsequent exposures
      to endotoxin, a phenomenon that is termed 'endotoxin tolerance'. Endotoxin
      tolerance increases the risks of secondary infection and mortality in patients
      with sepsis. In endotoxin-tolerant macrophages, the mixed variation of gene
      transcription is referred to as macrophage reprogramming. The mechanisms
      underlying macrophage reprogramming remain unclear at present. Interferon-induced
      double-stranded RNA-dependent protein kinase (PKR) is a widely expressed
      serine/threonine protein kinase. In addition to antiviral effects, PKR regulates
      the transcription of inflammatory cytokines by affecting transcription factors.
      However, the role of PKR in macrophage reprogramming remains to be elucidated. In
      the present study, the expression of inflammatory cytokines differed in
      lipopolysaccharide (LPS)-tolerant RAW264.7 macrophages compared with LPS
      activated macrophages. Specifically, reverse transcription-quantitative
      polymerase chain reaction results demonstrated that the mRNA levels of tumor
      necrosis factor-alpha, interleukin-1beta (IL-1beta), C-X-C motif chemokine ligand
      11, C-C motif chemokine ligand (CCL17), CCL22 and suppressor of cytokine
      signaling 3 were decreased, and mRNAs levels of arginase-1 (Arg1) and nitric
      oxide synthase 2 (iNOS) were increased, in LPS-tolerant macrophages compared with
      LPS-activated macrophages. Furthermore, western blot analysis demonstrated that
      the protein levels of phosphorylated (p)-PKR were significantly decreased in the
      LPS-tolerant cells. PKR activation with rotenone (10 uM) abrogated endotoxin
      tolerance by increasing the levels of the IL-1beta, CCL17 and CCL22 mRNAs and
      decreasing the levels of the Arg1 and iNOS mRNAs. Furthermore, western blotting
      demonstrated that AKT was markedly inactivated in endotoxin-tolerant cells, as
      indicated by reduced p-AKT levels. However, levels of p-AKT were markedly
      increased following rotenone-induced PKR activation in endotoxin-tolerant cells.
      Ly294002 (10 uM), a phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/AKT
      signaling inhibitor, partially reversed the rotenone-induced alleviation of
      endotoxin tolerance. These results demonstrated that PKR inhibition mediated
      endotoxin tolerance in macrophages, and these effects were partially mediated by
      PI3K/AKT signaling. PKR may be a potential target for the treatment of endotoxin
      tolerance in patients with sepsis.

PMID- 29658573
TI  - Hedgehog signaling regulates the expression levels of inflammatory mediators in
      cigarette-induced airway inflammation.
AB  - Chronic obstructive pulmonary disease (COPD) is a persistent airway inflammation
      influenced by cigarette smoke. Previous studies have reported that Hedgehog (Hh)
      signaling is aberrantly activated by cigarette smoke and dysregulated in COPD.
      The present study explored the role of the Hh signaling pathway on the expression
      levels of certain inflammatory mediators in cigarette-induced airway
      inflammation. Herein, a total of three A549 cell populations were generated: The
      A0 group as control cells, the A1 group cells treated with nicotine at a
      concentration of 10 uM for 12, 24 and 48 h, and the A2 group cultured
      simultaneously with nicotine and cyclopamine for the same duration. The total
      concentrations of the inflammatory mediators interleukin-6 (IL-6), IL-8 and tumor
      necrosis factor (TNF)-alpha, and an anti-inflammatory cytokine, IL-10, were
      assessed in all of the cells by ELISA and western blotting. The protein levels of
      sonic hedgehog (Shh), glioma-associated oncoprotein 1 (Gli1) and Smoothened (Smo)
      in nicotine-induced Hh signaling were also detected. The results indicated that
      A549 had increased levels of IL-6, IL-8 and TNF-alpha when cultured with nicotine
      when compared with the control cells. By contrast, the expression levels of these
      inflammatory mediators decreased with varying degrees when treated with
      cyclopamine that blocked the Hh signaling pathway. The IL-10 expression levels
      exhibited the reverse. The expressions of the Shh, Gli1 and Smo proteins were
      higher in the A1 group when compared with the control and decreased with
      cyclpoamine treatment. In conclusion, the Hh signaling pathway may partly have an
      impact on cigarette-induced airway inflammation via the regulation of
      inflammatory mediators. Thus, blocking Hh signaling and diminishing the airway
      inflammation reaction may serve as a potential therapy for COPD.

PMID- 29658574
TI  - Screening for implicated genes in colorectal cancer using whole-genome gene
      expression profiling.
AB  - To identify biologically relevant genes associated with the pathogenesis of
      colorectal cancer (CRC), genome wide expression profiles of 17 pairs of CRC tumor
      and adjacent tissues, previously published in a DNA microarray study, were
      analyzed. Cytoscape, String tools and DAVID tools were used to investigate the
      biological pathways encoded by the genes identified as being either upregulated
      or downregulated in CRC, to determine protein-protein interactions and to
      identify potential hub genes associated with CRC. As a result, a total of 3,264
      genes were identified as being differentially expressed in CRC and adjacent
      tissues, including 1,594 downregulated and 1,670 upregulated genes. Furthermore,
      306 genes were revealed to be clustered in a complex interaction network, and the
      top 20 hub genes in this network were determined by application of the Matthews
      Correlation Coefficient algorithm. In addition, the patterns of the expression
      levels of the 20 hub genes were investigated using reverse transcription
      quantitative polymerase chain reaction. Gene Ontology analysis revealed that four
      of the 20 hub genes encoded small subunit processome components (UTP3 small
      subunit processome component; UTP14 small subunit processome component; UTP 18
      small subunit processome component; and UTP20 small subunit processome component)
      and a further four encoded WD repeat domains (WD repeat-containing protein 3, WD
      repeat domain 12, WD repeat-containing protein 43 and WD repeat-containing
      protein 75). In conclusion, the present DNA microarray study identified genes
      involved in the pathogenesis of CRC. Furthermore, it was revealed that hub genes
      identified from among the total identified upregulated and downregulated genes in
      CRC encoding subunit processome components and WD repeat domains may represent
      novel target molecules for future treatments of CRC.

PMID- 29658575
TI  - Differences between carcinoma of the cecum and ascending colon: Evidence based on
      clinical and embryological data.
AB  - Developing rapidly from the cecal diverticulum in a 5-week-old embryo, the cecum,
      which is developed from the caudal limb of the midgut loop, is different from the
      ascending colon. The aim of this study was to analyze the different
      clinicopathological and biological characteristics of patients with carcinoma of
      the cecum and ascending colon. We accessed data for 59,035 patients with
      adenocarcinomas of the cecum and ascending colon from the Surveillance,
      Epidemiology and End Results database to explore the potential associations
      between the clinicopathological characteristics and overall survival.
      Furthermore, we analyzed the differences in gene expression between the two
      segments in the Gene Expression Omnibus database. The results were validated in
      The Cancer Genome Atlas database, as well as with another independent dataset
      from the First Affiliated Hospital of Xi'an Jiaotong University. The results of
      this study revealed the potential prognostic differences between adenocarcinoma
      of the cecum and ascending colon, which may be caused by the differential
      expression levels of the SLCO1B3 gene. When including the expression levels of
      SLCO1B3 in intraoperatively examined lymph nodes, 8 factors were found able to
      predict the prognosis of patients with carcinomas of the cecum and ascending
      colon. As regards the surgical therapeutic strategies, the resection of >15 local
      lymph nodes is appropriate for improving the prognosis of patients.

PMID- 29658576
TI  - Paclitaxel suppresses proliferation and induces apoptosis through regulation of
      ROS and the AKT/MAPK signaling pathway in canine mammary gland tumor cells.
AB  - Paclitaxel is a diterpenoid compound, derived from the pacific yew (Taxus
      brevifolia) berry, which exhibits antineoplastic effects against various types of
      cancer. However, the antitumor effects and the molecular mechanisms of paclitaxel
      on canine CHMm cells remain to be elucidated. The aim of the present study was to
      investigate the antitumor effects of paclitaxel on CHMm cells and identify
      relevant signal transduction pathways modulated by paclitaxel using multiple
      methods including MTT assay, flow cytometry, acridine orange/ethidium bromide
      staining, transmission electron microscopy, determination of cellular reactive
      oxygen species (ROS), superoxide dismutase (SOD) and malondiadehyde (MDA) and
      western blotting, the data indicated that paclitaxel decreased cell viability,
      induced G2/M-phase cell cycle arrest, suppressed the expression of cyclin B1 and
      induced apoptosis in a dose-dependent manner. In addition, paclitaxel upregulated
      the expression of Bax and cytochrome c, but reduced expression of apoptosis
      regulator Bcl-2, resulting in activation of caspase-3, chromatin condensation,
      karyopyknosis, intracellular vacuolization, increased production of ROS and MDA,
      and decreased activity of SOD. However, these effects were inhibited when CHMm
      cells were treated with N-acetyl-L-cysteine. Furthermore, treatment with
      paclitaxel inhibited the level of of phospho (p)-RAC-alpha serine/threonine
      protein kinase (AKT) and p-ribosomal protein S6 kinase proteins, and promoted
      phosphorylation of P38 mitogen-activated protein kinase (MAPK) and p-90 kDa
      ribosomal protein S6 kinase 1 proteins in CHMm cells. It was observed that
      paclitaxel in combination with pharmacological inhibitors of the P38 and
      phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) signaling pathways
      (SB203580 and LY294002, respectively) exerted synergistic inhibitory effects on
      the proliferation of the CHMm cells. The results of the present study
      demonstrated that paclitaxel inhibited tumor cell proliferation by increasing
      intrinsic apoptosis through inhibition of the PI3K/AKT signaling pathway and
      activation of MAPK signaling pathway in CHMm cells.

PMID- 29658577
TI  - Interleukin 29 activates expression of tissue inhibitor of metalloproteinase 1 in
      macrophages via toll-like receptor 2.
AB  - Obesity and diabetes are characterized by low grade chronic inflammation status
      and insulin resistance in adipose tissue associated with metalloproteinase
      inhibitor 1 (TIMP1). Interleukin (IL)29, exhibits multiple immune regulatory
      activities. However, the role of IL29 and its effects on TIMP1 remain to be
      elucidated. The present study was designed to investigate the effects of IL29 on
      expression of TIMP1 in macrophages associated with inflammation in adipose
      tissue. IL29 and high glucose were used to activate Raw264.7 cells and primary
      macrophages with or without antibody-mediated inhibition of toll like receptor
      (TLR) 2 and TLR4. TIMP1 was measured in culture media of Raw264.7 cells and
      primary macrophages by ELISA. IL29 and high glucose increased TIMP1 levels in
      Raw264.7 cells and primary macrophages. Antibody-mediated inhibition of TLR2 or
      TLR2 gene knockout decreased TIMP1 levels activated by IL29, however not by high
      glucose in the medium of Raw264.7 cells and primary macrophages. Furthermore,
      antibody-mediated inhibition of TLR4 or TLR4 gene knockout decreased TIMP1 levels
      which were stimulated by high glucose, not by IL29 in the medium of Raw264.7
      cells and primary macrophages. The results of the present study indicate that
      TLR2 is involved in IL29-stimulated TIMP1 expression in Raw264.7 cells and
      primary macrophages.

PMID- 29658578
TI  - Combined bioinformatics analysis reveals gene expression and DNA methylation
      patterns in osteoarthritis.
AB  - Osteoarthritis (OA) is a common type of arthritis, which may cause pain and
      disability. Alterations in gene expression and DNA methylation have been proven
      to be associated with the development of OA. The aim of the present study was to
      identify potential therapeutic targets and associated processes for OA via the
      combined analysis of gene expression and DNA methylation datasets. The gene
      expression and DNA methylation profiles were obtained from the Gene Expression
      Omnibus, and differentially expressed genes (DEGs) and differentially methylated
      sites (DMSs) were identified in the present study, using R programming software.
      The enriched functions of DEGs and DMSs were obtained via the Database for
      Annotation, Visualization and Integrated Discovery. Finally, cross analysis of
      DEGs and DMSs was performed to identify genes that exhibited differential
      expression and methylation simultaneously. The protein-protein interaction (PPI)
      network of overlaps between DEGs and DMSs was obtained using the Human Protein
      Reference Database; the topological properties of PPI network overlaps were
      additionally obtained. Hub genes in the PPI network were further confirmed via
      reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The
      results of the present study revealed that the majority of DEGs and DMSs were
      upregulated and hypomethylated in patients with OA, respectively. DEGs and DMSs
      were primarily involved in inflammatory, immune and gene expression regulation
      associated processes and pathways. Cross analysis revealed 30 genes that
      exhibited differential expression and methylation in OA simultaneously.
      Topological analysis of the PPI network revealed that numerous genes, including G
      protein subunit alpha1 (GNAI1), runt related transcription factor 2 (RUNX2) and
      integrin subunit beta2 (ITGB2), may be involved in the development of OA.
      Additionally, RT-qPCR analysis of GNAI1, RUNX2 and ITGB2 provided further
      confirmation. Numerous known and novel therapeutic targets were obtained via
      network analysis. The results of the present study may be beneficial for the
      diagnosis and treatment of OA.

PMID- 29658579
TI  - Identification of TYR mutations in patients with oculocutaneous albinism.
AB  - Oculocutaneous albinism (OCA) is a set of autosomal recessive disorders
      characterized by hypopigmented hair, skin and eyes. Homozygous or compound
      heterozygous mutations in the tyrosinase (TYR) gene can cause OCA1, which is the
      most common and severe subtype of albinism. In the present study, 17 patients
      with non-syndromic OCA were enrolled from eight provinces of China and were non
      consanguineous, with the exception of Patient 4000301. Total genomic DNA was
      isolated from peripheral blood. Screening was performed for the whole exons and
      their flanking regions of the TYR gene using Sanger sequencing and the
      pathogenicity of variants was predicted using in silico analysis. In total, 12
      TYR mutations were identified in 10 patients, respectively. Of these, two
      patients carried homozygous mutations and eight patients carried compound
      heterozygous mutations. Among the 12 TYR mutations, two missense mutations
      c.1198T>G (p.W400G) and c.819G>T (p.Q273H) were novel. The results of the present
      study expand the mutation spectrum of the TYR gene, which may further assist in
      the prenatal examination and genetic diagnosis of OCA.

PMID- 29658580
TI  - Norepinephrine inhibits the cytotoxicity of NK92-MI cells via the beta2
      adrenoceptor/cAMP/PKA/p-CREB signaling pathway.
AB  - Norepinephrine (NE) can regulate natural killer (NK) cell activity, but the
      mechanism remains unclear. In the present study the roles of adrenergic receptors
      (ARs) in inhibiting NK92-MI cells-mediated cytotoxicity by NE were investigated.
      To examine the effect of NE on NK92-MI cytotoxicity, a lactate dehydrogenase
      release cytotoxicity assay was used to determine the cytotoxicity of NK92-MI
      cells against K562 cells. To evaluate the possible function of the alpha, beta1
      and beta2 AR in mediating NE-induced effects, NK92-MI cells were pre-incubated
      with phenol-amine, CGP20712A and ICI118551 prior to stimulation by NE. To
      evaluate the role of cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA)
      signaling pathway in the inhibitory effect on cytotoxicity of NK92-MI cell by NE,
      NK92-MI cells were pre-incubated with PKA inhibitor Rp-8-Br-cAMP prior to
      stimulation by NE. It was demonstrated that NE decreased cytotoxicity and
      downregulated the expression of perforin, granzyme B and interferon (IFN)-gamma
      of NK92-MI cells in a dose-dependent manner. Blocking NE functional receptors by
      ARs antagonists, particularly of beta2 AR antagonist, suppressed the inhibitory
      effect of NE on cytotoxicity and expression of perforin, granzyme B, IFN-gamma of
      NK92-MI cells significantly. Blockade of beta2 AR in NE treated NK92-MI cells
      resulted in a reduction of the expression of phosphorylated (p)-cAMP-responsive
      element-binding protein (CREB) and intracellular cAMP concentration. Inhibiting
      the activity of PKA by Rp-8-Br-cAMP in NE treated NK92-MI cells resulted in
      increased cytotoxicity. The results of the present study suggest that NE can
      inhibit cytotoxicity and expression of perforin, granzyme B, IFN-gamma of NK92-MI
      cell mainly via the beta2-AR/cAMP/PKA/p-CREB signaling pathway.

PMID- 29658581
TI  - MicroRNA-146a/Toll-like receptor 4 signaling protects against severe burn-induced
      remote acute lung injury in rats via anti-inflammation.
AB  - The present study investigated the preventive effects of microRNA (miR)-146a
      against severe burn-induced remote acute lung injury (ALI) in rats and the
      underlying mechanism. The surface area of the skin was immersed in 100C water for
      5-10 sec on the dorsal surface. The expression level of miR-146a was
      significantly downregulated in rats with burn-induced ALI. Downregulation of miR
      146a increased inflammation, and inducible nitric oxide synthase (iNOS) and
      cyclooxygenase-2 (COX-2) expression in a model of ALI in vitro via the promotion
      of the Toll-like receptor (TLR)4/nuclear factor (NF)-kappaB signaling pathway. In
      addition, the overexpression of miR-146a reduced inflammation, and iNOS and COX-2
      protein expression in the model of ALI in vitro via the suppression of the
      TLR4/NF-kappaB signaling pathway. A TLR4 inhibitor reduced the function of anti
      miR-146a on inflammation in the model of ALI. Collectively, the results of the
      present study demonstrated the preventive effects of miR-146a against severe burn
      induced remote ALI in rats through the anti-inflammatory-regulated TLR4/NF-kappaB
      signaling pathway.

PMID- 29658582
TI  - Sirt1/Nrf2 signalling pathway prevents cognitive impairment in diabetic rats
      through anti-oxidative stress induced by miRNA-23b-3p expression.
AB  - In the present study the exact roles and mechanisms underlying the effect of
      miRNA-23b-3p on the cognitive impairment of diabetic rats were investigated. The
      in vivo model of diabetes was established in Wistar rats via a single injection
      of streptozotocin (STZ). Cognitive function was evaluated using a Morris water
      maze test. Oxidative stress was measured using ELISA kits, and the protein
      expression levels of B-cell lymphoma 2-associated X protein, silent information
      regulator 1 (SIRT1), nuclear factor erythroid 2-related factor 2 (Nrf2) and GAPDH
      were measured by western blot analysis. Micro (mi)RNA-23b-3p mimics were employed
      to increase miRNA-23b-3p expression in the in vitro model. Overexpression of
      miRNA-23b-3p increased oxidative stress (as indicated by the levels of
      glutathione peroxidase, glutathione, superoxide dismutase and malondialdehyde)
      and apoptosis in neurocytes following high-glucose treatment. The overexpression
      of miRNA-23b-3p also suppressed SIRT1 and Nrf2 expression in neurocytes following
      high-glucose treatment; it also promoted the SIRT1-induced inhibition of
      apoptosis and oxidative stress. The promotion of SIRT1 also decreased the effect
      of miRNA-23b-3p on cognitive impairment in diabetic rats. In conclusion, miRNA
      23b-3p prevents the cognitive impairment of diabetic rats via anti-oxidative
      stress effects and the Sirt1/Nrf2 signaling pathway.

PMID- 29658584
TI  - miR-145-5p reduces proliferation and migration of hepatocellular carcinoma by
      targeting KLF5.
AB  - MicroRNAs (miRs) are important in hepatocellular carcinoma (HCC) progression. miR
      145-5p acts as a tumor suppressor in certain malignancies, however, its role in
      HCC remains unclear. The present study aimed to perform a functional analysis of
      miR-145-5p in HCC in order to elucidate its role in the pathogenesis of HCC.
      Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was
      performed to analyze tissue and cellular expression of miR-145-5p in HCC.
      Following miRNA mimics transfection, cell viability, apoptosis and cells
      migration were determined by Cell Counting kit-8, Annexin V-FITC/propidium iodide
      staining and Transwell analyses. The target of miR-145-5p was analyzed by
      luciferase reporter assay and western blot analysis. It was observed that miR-145
      5p was significantly decreased in HCC tissues and cell lines. Overexpression of
      miR-145-5p significantly increased apoptosis, reduced cell proliferation and
      suppressed HCC cell migration. Kruppel-like factor 5 (KLF5) is regarded as a
      target of miR-145-5p in HCC cells. In addition, KLF5 overexpression partially
      attenuated the tumor suppressive effects of miR-145-5p. KLF5 expression was
      negatively associated with levels of miR-145-5p in HCC tissues. The present study
      demonstrated that miRNA-145-5p may, by targeting KLF5, partially suppress HCC
      cell growth and motility. The results of the present study suggested that miRNA
      145-5p alteration in HCC may serve a role in the progression of HCC.

PMID- 29658583
TI  - Intraductal papillary mucinous neoplasms of the pancreas: Clinical association
      with KRAS.
AB  - Intraductal papillary mucinous neoplasms of the pancreas (IPMN) are among the
      most important precancerous lesions in the pancreas. V-Ki-ras 2 Kirsten rat
      sarcoma viral oncogene homolog (KRAS) is one of the most important genes involved
      in pancreatic neoplasms, and exhibits a high mutation rate in pancreatic ductal
      adenocarcinomas and pancreatic intraepithelial neoplasia. The present study aimed
      to further elucidate the associations among IPMN subtypes (gastric, intestinal,
      pancreatobiliary and oncocytic), pathological classifications [low-grade,
      intermediate-grade, and high-grade IPMN, and associated minimally invasive
      carcinoma (invasive depth <=0.5 cm) and advanced invasive carcinoma (invasive
      depth >0.5 cm)]. A total of 56 cases of IPMN were studied using scorpion
      amplified refractory mutation system analysis of KRAS mutations, pathological
      features and prognosis. KRAS mutations were identified in 50% (28/56 cases). The
      frequency was 60% (9/15 cases) in gastric-type, 52.6% (10/19 cases) in intestinal
      type, 47.3% (9/19 cases) in pancreatobiliary-type and zero (0/3 cases) in
      oncocytic-type IPMN. Except for oncocytic type IPMN, the frequencies of KRAS
      mutations in IPMN with low, intermediate and high grade, and IPMN-associated
      carcinoma were 58.3% (7/12 cases), 27.3% (3/11 cases), 80% (4/5 cases) and 56%
      (14/25 cases), respectively. With more advanced dysplasia and invasion, the
      prevalence of KRAS mutations in intestinal-type IPMN increased (P=0.012). The
      Kaplan-Meier survival curve demonstrated that survival rate was not associated
      with KRAS mutation (log-rank test; P=0.308). The prevalence of KRAS mutations was
      lowest in intestinal-type IPMN, and was in proportion to the degree of dysplasia
      and invasion. Therefore, KRAS mutation in IPMN does not correlate with
      histological subtype, dysplasia grade, depth of invasion or survival.

PMID- 29658585
TI  - Inhibitors of heat shock protein 90 augment endothelin-1-induced heat shock
      protein 27 through the SAPK/JNK signaling pathway in osteoblasts.
AB  - It has been previously reported that endothelin-1 (ET-1) stimulates the induction
      of heat shock protein (HSP) 27 through the activation of p38 mitogen-activated
      protein (MAP) kinase and stress-activated protein kinase/c-Jun N-terminal kinase
      (SAPK/JNK) in osteoblast-like MC3T3-E1 cells. The present study investigated
      whether HSP90, a high-molecular-weight HSP, was implicated in the ET-1-stimulated
      HSP27 induction in MC3T3-E1 cells. The effects of HSP90 inhibitors on the
      induction of HSP27 were examined. The HSP90 inhibitors geldanamycin and 17
      demethoxygeldanamycin (17-DMAG) significantly amplified HSP27 induction
      stimulated by ET-1 in a dose-dependent manner. In addition, onalespib (another
      HSP90 inhibitor) significantly strengthened the ET-1-induced HSP27 protein
      levels. The ET-1-stimulated phosphorylation of p38 MAP kinase was minimally
      affected by geldanamycin, 17-DMAG or onalespib. Onalespib and 17-DMAG
      significantly enhanced the ET-1-induced phosphorylation of SAPK/JNK. In addition,
      SP600125, a SAPK/JNK inhibitor, notably reduced the amplification by onalespib of
      ET-1-induced HSP27. These results suggest that HSP90 limits ET-1-stimulated HSP27
      induction at a point upstream of SAPK/JNK in osteoblasts. These results suggest
      that HSP90 may be a novel clinical target for metabolic bone diseases, including
      osteoporosis.

PMID- 29658586
TI  - Preparation and characterization of calcium carbonate microspheres and their
      potential application as drug carriers.
AB  - The influence of lecithin from egg yolk (LE) on calcium carbonate (CaCO3)
      biomineralization was investigated. In the present study, spherical CaCO3
      particles were synthesized via coprecipitation in the presence of LE. LE
      multilamellar liposomes were first tuned by sonication to provide better control
      over the nucleation of CaCO3. Subsequently, monodisperse microspheres ~2 um in
      size were generated by controlling the aggregation and growth of CaCO3 under
      appropriate concentrations of LE. In contrast to unstable vaterite, the
      microspheres generated in aqueous solution remained stable for at least 10 days
      without transforming into calcite, due to the strong interaction between the LE
      and calcium ions. The microspheres as drug carriers of doxorubicin (DOX) were
      assessed and were observed to have a good encapsulation efficiency, sustained
      drug release without a burst release and notable pH sensitivity. In addition, in
      vivo tumor inhibition examination demonstrated that DOX-loaded CaCO3 microspheres
      formulation had more superior efficacy to significantly restrain tumor growth.
      These novel LE/CaCO3 hybrids may provide novel options for various biomedical
      applications.

PMID- 29658588
TI  - Autophagy inhibition potentiates SAHA-mediated apoptosis in glioblastoma cells by
      accumulation of damaged mitochondria.
AB  - Glioblastoma multiforme (GBM), often referred to as a grade IV astrocytoma, is
      the most invasive type of tumor arising from glial cells. The main treatment
      options for GBM include surgery, radiation and chemotherapy. However, these
      treatments tend to be only palliative rather than curative. Poor prognosis of GBM
      is due to its marked resistance to standard therapy. Currently, temozolomide
      (TMZ), an alkylating agent is used for treatment of GBM. However, GBM cells can
      repair TMZ-induced DNA damage and therefore diminish the therapeutic efficacy of
      TMZ. The potential to evade apoptosis by GBM cells accentuates the need to target
      the non-apoptotic pathway and/or inhibition of pro-survival strategies that
      contribute to its high resistance to conventional therapies. In recent studies,
      it has been demonstrated that HDAC inhibitors, such as vorinostat (suberoyl
      anilide hydroxamic acid; SAHA) can induce autophagy in cancer cells, thereby
      stimulating autophagosome formation. In addition, a lysosomotropic agent such as
      chloroquine (CQ) can result in hyper-accumulation of autophagic vacuoles by
      inhibiting autophagosome-lysosome fusion, which can drive the cell towards
      apoptosis. Hence, we postulated that combination treatment with SAHA and CQ may
      lead to increased formation of autophagosomes, resulting in its hyper
      accumulation and ultimately inducing cell death in GBM cells. In the present
      study, we demonstrated that CQ co-treatment enhanced SAHA-mediated GBM cell
      apoptosis. Inhibition of the early stage of autophagy by 3-methyladenine pre
      treatment reduced cell death confirming that apoptosis induced by CQ and SAHA was
      dependent on autophagosome accumulation. We also demonstrated that autophagy
      inhibition led to enhanced ROS, mitochondria accumulation and reduced
      mitochondrial membrane potential resulting in cell death. The present study
      provides cellular and molecular evidence concerning the combined effect of SAHA
      and CQ which can be developed as a therapeutic strategy for the treatment of
      glioblastoma in the future.

PMID- 29658587
TI  - Androgen receptor-mediated upregulation of quaking affects androgen receptor
      related prostate cancer development and anti-androgen receptor therapy.
AB  - The androgen receptor (AR) has a crucial role in prostate cancer. RNA-binding
      protein-mediated post-transcriptional regulation is important in the initiation
      and development of cancer. The present study attempted to elucidate the mutual
      association of AR and RNA-binding protein quaking (QKI) in the development of
      prostate cancer. Dual-luciferase reporter demonstrated that AR can positively
      regulate the expression of QKI in prostate cancer cell lines due to its effective
      transcription regulating function. In addition, QKI may increase expression of AR
      by heat shock protein 90, which is a coactivator of AR, and silencing QKI can
      increase the sensitive of Casodex, which is an antagonist of AR in castration
      resistant prostate cancer. This may be a new strategy for advanced prostate
      cancer.

PMID- 29658589
TI  - Autophagy regulation and its dual role in blood cancers: A novel target for
      therapeutic development (Review).
AB  - Autophagy, a physiological process in which cellular components are degraded by
      the lysosome for cell homeostasis, plays an important role in cell metabolism,
      including cell proliferation, differentiation, survival and apoptosis. Recent
      studies indicate that autophagy serves as a survival mechanism by eliminating
      misfolded proteins and attenuating DNA damage. Autophagy can also suppress tumor
      growth, depending upon the cell context and functional status. Dysfunction of
      autophagy may be closely linked to the initiation and development of various
      diseases, including hematological malignancies. Mounting evidence highlights the
      dual role of autophagy in blood cancers through multifarious signal pathways.
      Therefore, strategies targeting autophagy will develop innovative therapeutic
      approaches for blood cancers, improve the efficacy of chemotherapy, and bring
      significant benefits for patients.

PMID- 29658590
TI  - Cucurbitacin D impedes gastric cancer cell survival via activation of the iNOS/NO
      and inhibition of the Akt signalling pathway.
AB  - Cucurbitacin D (CuD), isolated from plants from the Cucurbitaceae family, is a
      potential antitumour agent since it inhibits proliferation, migration and
      metastasis of cancer cells. Despite CuD antitumour activity in cancer cells, the
      effects of CuD on gastric cancer cell lines remain unclear. The present study
      aimed to investigate the effects of CuD on gastric cancer cell growth and death.
      Human gastric cancer cell lines (AGS, SNU1 and Hs746T) were cultured and treated
      with different concentrations of CuD (0, 0.25, 0.5, 1 and 2 uM). Cell
      proliferation was assessed using Cell Counting Kit-8 assay. Oxidative stress was
      evaluated by generation of reactive oxygen species (ROS). Cell apoptosis was
      assessed by terminal deoxynucleotidyl transferase 2'-deoxyuridine-5'-triphosphate
      nick-end labelling (TUNEL) staining. Levels of intracellular Ca2+ and adenosine
      triphosphate (ATP) were also assessed. In the present study, CuD effectively
      inhibited cell proliferation, triggered ROS generation and induced apoptosis in
      gastric cancer cells (AGS, SNU1 and Hs746T). Treatment with CuD increased
      intracellular Ca2+ and ATP levels. CuD also stimulated the expression of
      inducible nitric oxide synthase (iNOS), which augmented nitric oxide production.
      In addition, CuD activated the mitochondrial apoptosis pathway, which increased
      the expression of Bax and the release of cleaved caspace-9 (C-caspase-9) and
      cytochrome c, decreased the expression of B-cell lymphoma 2 (Bcl-2). The
      mechanism of action of CuD involved the regulation of the protein kinase
      B/mechanistic target of rapamycin (Akt/mTOR) pathway. We confirmed the effects of
      CuD on gastric tumours via an in vivo xenograft gastric tumour model. In
      conclusion, CuD inhibited Akt and activated the iNOS pathway, leading to higher
      ROS and nitric oxide production, which accelerated gastric cancer cell apoptosis.

PMID- 29658591
TI  - The biological role of autophagy in regulating and controlling the proliferation
      of liver cancer cells induced by bufalin.
AB  - Autophagy is an important mechanism which regulates the processes of cell growth
      and death. The biological role of autophagy in regulating and controlling the
      proliferation of liver cancer cells by bufalin remains unknown. In the present
      study we investigated the effect of bufalin on autophagy of liver cancer cells.
      The growth inhibition and autophagy of liver cancer cells were detected using
      acridine orange fluorescence staining, flow cytometry and transmission electron
      microscopy. Combined with autophagy inhibitors (3-MA and CQ), CCK8 staining and
      western blot analysis were used to detect the effect of bufalin on the
      proliferation and autophagy-related protein expression in HCC-LM3 cells at the
      indicated time-points. Results indicated that combined with autophagy inhibitors
      3-MA and CQ, the inhibitive effect of bufalin on the proliferation of HCC-LM3
      cells was significantly enhanced. When combined with autophagy inhibitors 3-MA or
      CQ, bufalin significantly reduced the autophagosome and acidic vesicles in HCC
      LM3 cells. When combined with autophagy inhibitors 3-MA and/or CQ for 12 h,
      bufalin significantly inhibited the expression of LC3-I and Beclin-1 in HCC-LM3
      cells, and upregulated the expression of LC3-II and P62 in HCC-LM3 cells. When
      combined with autophagy inhibitors 3-MA and/or CQ for 24 h, bufalin significantly
      inhibited the LC3-II expression in HCC-LM3 cells, and upregulated the LC3-I, P62
      and Beclin-1 expression in HCC-LM3 cells. When combined with autophagy inhibitors
      3-MA and/or CQ for 48 h, bufalin significantly inhibited the expression of LC3-II
      and Beclin-1 in HCC-LM3 cells, and upregulated the expression of LC3-I and P62 in
      HCC-LM3 cells. These findings indicated that bufalin induced cell autophagy and
      inhibited proliferation of liver cancer cells by influencing the expression of
      autophagy related proteins including LC3-I, LC3-II, P62 and Beclin-1 in liver
      cancer cells. The autophagic state of liver cancer cells affected the inhibitory
      effect of bufalin on the proliferation of liver cancer cells.

PMID- 29658592
TI  - In vitro cytotoxic effect of PARP inhibitor alone and in combination with nab
      paclitaxel on triple-negative and luminal A breast cancer cells.
AB  - In the present study, the in vitro cytotoxic effect of poly(ADP-ribose)
      polymerase (PARP) inhibitor alone and in combination with nab-paclitaxel was
      evaluated on human triple-negative breast cancer (TNBC) cell line MDA-MB-231 and
      human luminal A breast cancer cell line MCF-7. For this purpose, cell index (CI)
      values obtained from xCELLigence Real-Time Cell Analysis (RTCA) DP instrument,
      mitotic index (MI), labelling index (LI) and apoptotic index (AI) analysis among
      cell kinetic parameters were used. As a result of PARP inhibitor application,
      there was a significant decrease in CI, MI and LI and a significant increase in
      AI for all the experimental groups. After application of PARP inhibitor in
      combination with nab-paclitaxel, the CI values were decreased for both cell
      lines, and the differences between the control and all the experimental groups
      were statistically significant (P<0.01) for all applications. PARP inhibitor,
      alone or in combination with nab-paclitaxel offers a promising treatment modality
      in different breast cancer subtypes.

PMID- 29658593
TI  - Laterally spreading features of gastrointestinal stromal tumors: A
      clinicopathological study.
AB  - To elucidate the histopathological features of laterally spreading
      gastrointestinal stromal tumors (GISTs), we retrospectively examined 52 GISTs
      grossly completely resected from 50 patients. Laterally spreading features were
      identified in 7 GISTs (13%), and were localized within non-thickened regions of
      the muscularis propria adjacent to the main GISTs, ranging in length from 0.12 to
      0.7 cm (mean, 0.3 cm). The laterally spreading features involved the muscular
      surgical margins in 2 cases. The morphologies of the laterally spreading cells
      resembled those of tumor cells in 4 cases, but were comprised of more slender
      spindle cells with smaller nuclei compared with those in the respective main
      GISTs. Compared with the main GISTs, KIT+ and discovered on GIST 1+
      immunostaining features of the spreading lesions were similar in 4 cases, and
      were weaker or diminished in the other 3 cases. There were no differences in
      CD34+ staining features between the main GISTs and the laterally spreading
      lesions. One patient with laterally spreading GIST succumbed to the disease 2.5
      years after the surgery, while the other 6 patients were alive without the
      recurrence of disease 0.4-19.2 years after the surgery. The laterally spreading
      features were associated with a pedunculated GIST (P=0.006), but not older age
      (P=0.312), sex (P=0.969), tumor size (P=0.430), mucosal invasion (P=0.666) or
      higher risk category (P=0.872). Results of the present study indicate that
      resection of a >=1-cm muscular safety margin, and not mucosa or submucosa, is
      required for microscopically negative surgical margins, particularly for
      pedunculated GISTs.

PMID- 29658594
TI  - Age-dependent decreases in insulin-like growth factor-I and its receptor
      expressions in the gerbil olfactory bulb.
AB  - Insulin-like growth factor-I (IGF-I) is a multifunctional protein present in the
      central nervous system. A number of previous studies have revealed alterations in
      IGF-I and its receptor (IGF-IR) expression in various regions of the brain.
      However, there are few reports on age-dependent alterations in IGF-I and IGF-IR
      expressions in the olfactory bulb, which contains the secondary neurons of the
      olfactory system. The present study examined the cellular morphology in the
      olfactory bulb by using cresyl violet (CV) staining at postnatal month (PM) 3 in
      the young group, PM 6 in the adult group and PM 24 in the aged group in gerbils.
      In addition, detailed examinations were performed of the protein levels and
      immunoreactivities of IGF-I and IGF-IR in the olfactory bulb in each group. There
      were no significant changes in the cellular morphology between the three groups.
      The protein levels and immunoreactivities of the IGF-I and IGF-IR were the
      highest in the young group and they decreased with age. He protein levels and
      immunoreactivities of the IGF-I and IGF-IR were the lowest in the aged group. In
      brief, our results indicate that IGF-I and IGF-IR expressions are strong in young
      olfactory bulbs and significantly reduced in aged olfactory bulbs. In conclusion,
      subsequent decreases in IGF-I and IGF-IR expression with age may be associated
      with olfactory decline. Further studies are required to investigate the roles of
      IFG-I and IGF-IR in disorders of the olfactory system.

PMID- 29658595
TI  - Huaier suppresses proliferative and metastatic potential of prostate cancer PC3
      cells via downregulation of Lamin B1 and induction of autophagy.
AB  - Prostate cancer is one of the most common malignancies occurring in males.
      Although large advances have been made in the pathogenesis of prostate cancer,
      the development of drugs with high efficacy and low toxicity for the treatment of
      prostate cancer is urgently needed. Recently, more and more attention has been
      paid to the antitumor effect of Traditional Chinese Medicine (TCM) worldwide.
      Trametes robiniophila Murr. (Huaier) has been applied as a type of TCM drug for
      ~1,600 years. Huaier exhibits excellent clinical efficacy in the treatment of
      cancer, including prostate cancer. However, the mechanisms underlying the anti
      prostate cancer effect of Huaier remain largely unclear. In the present study, we
      revealed that Huaier aqueous extract inhibited the proliferative and metastatic
      capabilities of human prostate cancer PC3 cells through CCK-8 assay, in vitro
      scratch assay and Transwell assay. Moreover, decreased Lamin B1 was implicated in
      Huaier-induced suppression of proliferative and metastatic potential of PC3
      cells. Intriguingly, we demonstrated that Huaier treatment induced autophagic
      cell death in PC3 cells. This study sheds new light on the mechanisms underlying
      the activity of Huaier against prostate cancer and provides a new theoretical
      basis for the clinical application of Huaier in prostate cancer.

PMID- 29658596
TI  - MicroRNA-616 promotes the progression of ovarian cancer by targeting TIMP2.
AB  - MicroRNAs (miRNAs), a group of short (~20 nt) non-coding RNAs, play critical
      roles in the development and progression of ovarian cancer (OC). The role of miR
      616, a recently identified cancer-associated miRNA, has never been examined in OC
      before. The present study demonstrated that the level of miR-616 was increased in
      OC tissues. A high miR-616 level was associated with poor tumor differentiation
      and advanced tumor-node-metastasis (TNM) stage. Survival analysis revealed that
      an elevated level of miR-616 was associated with poor prognosis of OC patients as
      demonstrated by decreased overall survival (OS) and disease-free survival (DFS).
      Overexpression of miR-616 promoted the migration, invasion as well as epithelial
      mesenchymal transition (EMT) of A2780 cells. Knockdown of miR-616 inhibited these
      biological functions. Immunohistochemical (IHC) staining revealed that OC tissues
      with high miR-616 levels exhibited a significantly decreased level of E-cadherin
      and an increased level of N-cadherin. Furthermore, tissue inhibitor of
      metalloproteinases 2 (TIMP2) was confirmed to be a direct downstream target of
      miR-616. Inhibition of TIMP2 expression was required for the promoting effects of
      miR-616 on the metastasis and EMT of OC cells. Collectively, this study revealed
      that miR-616 promoted the progression of OC by enhancing cell migration, invasion
      and EMT.

PMID- 29658597
TI  - Antitumoral effect of Ocoxin, a natural compound-containing nutritional
      supplement, in small cell lung cancer.
AB  - Lung cancer is the most frequently diagnosed neoplasia and represents the leading
      cause of cancer-related deaths worldwide. Due to this fact, efforts to improve
      patient survival through the introduction of novel therapies, as well as
      preventive actions, are urgently required. Considering this scenario, the
      antitumoral action of the composite formulation Ocoxin(r) oral solution (OOS),
      that contains several antitumoral compounds including antioxidants, was tested in
      small cell lung cancer (SCLC) in vitro and in vivo preclinical models. OOS
      exhibited anti-SCLC action that was both time and dose dependent. In vivo OOS
      decreased the growth of tumors implanted in mice without showing signs of
      toxicity. The antitumoral effect was due to inhibition of cell proliferation and
      increased cell death. Genomic and biochemical analyses indicated that OOS
      augmented p27 and decreased the functioning of several routes involved in cell
      proliferation. In addition, OOS caused cell death by activation of caspases.
      Importantly, OOS favored the action of several standard of care drugs used in the
      SCLC clinic. Our results suggest that OOS has antitumoral action on SCLC, and
      could be used to supplement the action of drugs commonly used to treat this type
      of tumor.

PMID- 29658598
TI  - Protein kinase, membrane-associated tyrosine/threonine 1 is associated with the
      progression of colorectal cancer.
AB  - The protein kinase, membrane-associated tyrosine/threonine 1 (PKMYT1) is known to
      inhibit precocious entry into mitosis by phosphorylating CDK1 at Thr14 and Tyr15
      residues. However, the functional importance of PKMYT1 in colorectal cancer (CRC)
      remains unknown. Thus, it is important to elucidate whether PKYMT1 is
      indispensable in the tumorigenesis of CRC. To investigate the functional
      importance of PKMYT1 in CRC tumorigenesis, PKMYT1 was knocked down in CRC cell
      lines such as SW480, SW620, HCT116 and HT29 by siRNA. PKMYT1-depleted CRC cells
      were analyzed to determine proliferation, migration, invasion and colony forming
      ability. In addition, 179 patient-derived samples were used to find the
      correlation of the expression of PKMYT1 with the prognosis of CRC patients. By
      siRNA-mediated loss of function of PKMYT1, we observed that proliferation,
      migration, invasion and colony forming ability of CRC cell lines were
      significantly impaired in the absence of PKMYT1 in vitro. Furthermore, by
      analyzing patient-derived samples, we revealed the association of PKMYT1 with the
      overall survival rate of CRC patients. These results indicated that PKMYT1 plays
      an essential oncogenic role in CRC and could serve as a good therapeutic target
      for the treatment of CRC.

PMID- 29658599
TI  - Screening potential biomarkers for colorectal cancer based on circular RNA chips.
AB  - The aim of the present study was to screen colorectal cancer (CRC) tissue and
      adjacent tissue for differences in circular RNA (circRNA) expression, to analyze
      the related miRNAs and messenger RNAs (mRNAs), and to investigate the circRNA
      expression in CRC and its function. The circRNA expression profile was generated
      using CapitalBio microarray technology. The differentially expressed circRNAs
      were identified with GeneSpring 12.5 software. Subsequently, the related mRNAs of
      the differentially expressed circRNAs were annotated with the molecule annotation
      system (MAS) 3.0, and the diseases, pathways and functional enrichment analysis
      of these mRNAs were performed using the KEGG orthology-based annotation system
      (KOBAS) 3.0. In addition, the target miRNAs of differentially expressed circRNAs
      were screened using the miRanda algorithm. The circRNA/miRNA network was
      constructed for the top 8 most significant differentially expressed circRNAs with
      Cytoscape software 3.4.0. A total of 10,245 differentially expressed circRNAs
      were identified, including 6,264 upregulated ones, and 3,981 downregulated ones.
      The related mRNAs were enriched in 462 KEGG diseases, 411 FunDO, 669 NHGRI GWAS
      catalog, and 845 OMIM; and 1,334 Reactomes, 281 KEGG pathways, 117 PANTHER and
      193 BioCyc; and 11,606 Gene Ontology (GO) terms. A total of 133 circRNA/miRNA
      pairs were involved in the circRNA/miRNA network. hsa_circ_0126897_CBC1 may be a
      potential biomarker for CRC, and the cell cycle was closely associated with the
      occurrence and development of CRC.

PMID- 29658600
TI  - PDK1 inhibitor GSK2334470 synergizes with proteasome inhibitor MG-132 in multiple
      myeloma cells by inhibiting full AKT activity and increasing nuclear accumulation
      of the PTEN protein.
AB  - Phosphoinositide-dependent kinase 1 (PDK1) is generally active in multiple
      myeloma (MM) and higher expression than other hematopoietic cells, which is
      associated with the drug resistance and the disease progression. Previous studies
      have demonstrated that PDK1 can be targeted therapeutically in MM. In the present
      study, we examined the combination effect of GSK2334470 (GSK-470), a novel and
      highly specific inhibitor of PDK1, with proteasome inhibitor MG-132 in MM cell
      lines. GSK-470 monotherapy significantly inhibited growth of MM cell lines and
      induced apoptosis that was associated with the activation of both the intrinsic
      mitochondrial pathway and the extrinsic death receptor pathway. Moreover, GSK-470
      demonstrated synergistic growth inhibitory effects with MG-132. Notably,
      treatment with these inhibitors resulted in an almost complete inhibition of
      phosphorylation of mammalian target of rapamycin on Ser2448 and Ser2481 and full
      activation of AKT. The combination therapy also caused an upregulation of PTEN
      and an increased nuclear accumulation of PTEN protein. Collectively, our results
      provide the rationale for novel combination treatment with PDK1 inhibitor and
      proteasome inhibitors to improve outcomes in patients with MM.

PMID- 29658601
TI  - Silencing of casein kinase 2 inhibits PKC-induced cell invasion by targeting MMP
      9 in MCF-7 cells.
AB  - Casein kinase 2 (CK2) is a serine/threonine protein kinase that has been
      considered to represent an important factor in mammary tumorigenesis. Increased
      expression of matrix metalloproteinase-9 (MMP-9) via nuclear factor-kappaB (NF
      kappaB) activation has been demonstrated to promote breast cancer cell invasion.
      In the present study, the involvement of CK2 in protein kinase C (PKC) induced
      cell invasion in MCF-7 breast cancer cells was investigated as well as the
      underlying molecular mechanisms. The mRNA and protein levels of MMP-9 in MCF-7
      cells were investigated using reverse transcription-quantitative polymerase chain
      reaction, western blot analyses and a zymography assay. Cell invasiveness was
      investigated using a Matrigel invasion assay, and it was revealed that small
      interfering RNA specific for CK2 suppressed PKC induced cell invasion by
      regulating MMP-9 expression via activation of the p38 kinase/c-Jun N-terminal
      kinase/NF-kappaB pathway. In addition, it was demonstrated that CK2 inhibitors
      [apigenin (20 uM), emodin (20 uM) or 2-dimethylamino-4,5,6,7-tetrabromo-1H
      benzimidazole (2 uM)] suppressed PKC induced cell invasion and MMP-9 expression.
      The results of the present study suggested that CK2 is an important factor
      involved in the induction of MCF-7 breast cancer cell invasion by PKC. Therefore,
      CK2 may represent novel candidates for therapy intended to inhibit invasion in
      breast cancer.

PMID- 29658602
TI  - Expression and significance of autonomic nerves and alpha9 nicotinic
      acetylcholine receptor in colorectal cancer.
AB  - The present study evaluated the distribution of sympathetic and parasympathetic
      nerves and the expression of the alpha9 nicotinic acetylcholine receptor
      (alpha9nAChR) and investigated their potential association with colorectal cancer
      (CRC) development. The distribution of autonomic nerves and alpha9nAChR in CRC
      was detected by immunohistochemistry, which was then used to analyze their
      association with clinicopathological parameters and prognosis. Sympathetic fibers
      were primarily observed in the stroma adjacent to cancer cells, whereas
      parasympathetic fibers were primarily observed in the stroma away from cancer
      cells. Patients with samples positive for sympathetic nerve fibers had less lymph
      node invasion and a better prognosis compared with patients with samples negative
      for sympathetic nerve fibers. The expression of parasympathetic nerves in
      patients >60 years old was increased compared with patients <=60 years old. The
      expression of parasympathetic nerves in patients with lymph node invasion was
      increased compared with patients without lymph node invasion. The detection of
      parasympathetic nerves gradually increased as CRC (T stage) advanced. Patients
      with parasympathetic negative samples had better prognoses compared with patients
      with parasympathetic positive samples. The expression of alpha9nAChR was
      principally localized in cellular membranes and the cytoplasm of CRC tissues and
      it was revealed to have a positive association with the number of parasympathetic
      nerves. Increased alpha9nAChR expression was observed in patients >60 years old
      compared with patients <60 years old. The detection rate of alpha9nAChR in
      tissues from patients with lymph node invasion was increased compared with
      patients without lymph node invasion. The detection of alpha9nAChR gradually
      increased as the CRC stage advanced. The prognoses for patients with alpha9nAChR
      negative tissue were improved compared with the prognoses for patients with
      alpha9nAChR positive tissue. Sympathetic nerves were primarily detected in the
      early phases of CRC and indicated a good prognosis. Parasympathetic nerves and
      alpha9nAChR were principally observed in the late phases of cancer and indicated
      a poor prognosis. The present study revealed that parasympathetic nerves may
      promote the progression of CRC through alpha9nAChR.

PMID- 29658603
TI  - Anticancer effect of exogenous hydrogen sulfide in cisplatin-resistant A549/DDP
      cells.
AB  - Despite huge advances in lung cancer treatment, resistance to cisplatin-based
      chemotherapy remains one of the major obstacles, and the elucidation of cisplatin
      resistance remains challenging. As an important biological and pharmacological
      mediator, hydrogen sulfide (H2S) performs a variety of homeostatic functions
      related to cancer formation and development. However, the effects of H2S on
      cisplatin-resistance lung cancer remain largely unknown. In the present study, we
      investigated the anticancer effects and relevant mechanisms of NaHS (an exogenous
      donor of H2S) on A549/DDP cells (cisplatin-resistant). The intracellular H2S was
      first evaluated using a fluorescence probe in A549 (cisplatin-sensitive) and
      A549/DDP cells. We found that H2S production was markedly decreased in A549/DDP
      cells compared with that in A549 cells, accomplished by the downregulation of
      cystathionine beta-synthase (CBS), an endogenous H2S-producing enzyme. In view of
      these findings, we then observed the effects of NaHS treatment on A549/DDP cells.
      The results showed that NaHS exposure exhibited an inhibitory effect on cell
      viability and the IC50 of cisplatin in A549/DDP cells decreased markedly during
      NaHS treatment (800 umol/l). In addition, our data revealed that NaHS treatment
      of A549/DDP cells resulted in the induction of apoptosis, cell cycle arrest and
      inhibition of cell migration and invasion. Finally, we demonstrated that the
      marked changes in the A549/DDP cell response to NaHS may be triggered by the
      activation of p53, and overexpression of p21, caspase-3, Bax and MMP-2, as well
      as the downregulation of Bcl-xL. The findings of the present study provide novel
      evidence that NaHS administration may represent a new strategy for the treatment
      of cisplatin-resistant lung cancer.

PMID- 29658604
TI  - Oncogenic miR-96-5p inhibits apoptosis by targeting the caspase-9 gene in
      hepatocellular carcinoma.
AB  - The aberrant expression or alteration of microRNAs (miRNAs/miRs) contributes to
      the development and progression of cancer. In the present study, the functions of
      miR-96-5p in hepatocellular carcinoma (HCC) were investigated. It was identified
      that miR-96-5p expression was significantly upregulated in primary HCC tumors
      compared with their non-tumorous counterparts. A copy number gain was frequently
      observed at chromosomal region 7q32.2 in which the MIR96 locus is located,
      suggesting that gene amplification may be one of the mechanisms by which miR-96
      5p expression is increased in HCC. Transfection of miR-96-5p mimic into HCC cells
      decreased the expression of CASP9, which encodes caspase-9, the essential
      initiator caspase in the mitochondrial apoptotic pathway, at the mRNA and protein
      levels. A putative binding site for miR-96-5p was identified in the CASP9 3'
      untranslated region, and the results of a luciferase assay indicated that CASP9
      is a potential direct target of miR-96-5p. The miR-96-5p mimic increased
      resistance to doxorubicin- and ultraviolet-induced apoptosis through the decrease
      in caspase-9 expression in HCC cells. Transfection of miR-96-5p inhibitor
      enhanced the cytotoxic effect of doxorubicin by increasing caspase-9 expression
      in the HCC cells, suggesting a synergistic effect between the miR-96-5p inhibitor
      and doxorubicin. In conclusion, the results of the present study suggest that miR
      96-5p, which is frequently upregulated in HCC, inhibits apoptosis by targeting
      CASP9. Therefore, miR-96-5p may be a potential therapeutic target for HCC.

PMID- 29658605
TI  - Aerobic exercise regulates blood lipid and insulin resistance via the toll-like
      receptor 4-mediated extracellular signal-regulated kinases/AMP-activated protein
      kinases signaling pathway.
AB  - Diabetes mellitus is a complicated metabolic disease with symptoms of
      hyperglycemia, insulin resistance, chronic damage and dysfunction of tissues, and
      metabolic syndrome for insufficient insulin production. Evidence has indicated
      that exercise treatments are essential in the progression of type-II diabetes
      mellitus, and affect insulin resistance and activity of islet beta-cells. In the
      present study, the efficacy and signaling mechanism of aerobic exercise on blood
      lipids and insulin resistance were investigated in the progression of type-II
      diabetes mellitus. Body weight, glucose metabolism and insulin serum levels were
      investigated in mouse models of type-II diabetes mellitus following experienced
      aerobic exercise. Expression levels of inflammatory factors, interleukin (IL)-6,
      high-sensitivity C-reactive protein, tumor necrosis factor-alpha and leucocyte
      differentiation antigens, soluble CD40 ligand in the serum were analyzed in the
      experimental mice. In addition, expression levels of toll-like receptor 4 (TLR-4)
      were analyzed in the liver cells of experimental mice. Changes of oxidative
      stress indicators, including reactive oxygen species, superoxide dismutase,
      glutathione and catalase were examined in the liver cells of experimental mice
      treated by aerobic exercise. Expression levels and activity of extracellular
      signal-regulated kinases (ERK) and AMP-activated protein kinase (AMPK) signaling
      pathways were investigated in the liver cells of mouse models of type-II diabetes
      mellitus after undergoing aerobic exercise. Aerobic exercise decreased the
      expression levels of inflammatory factors in the serum of mouse models of type-II
      diabetes mellitus. The results indicated that aerobic exercise downregulated
      oxidative stress indicators in liver cells from mouse models of type-II diabetes
      mellitus. In addition, the ERK and AMPK signaling pathways were inactivated by
      aerobic exercise in liver cells in mouse models of type-II diabetes mellitus. The
      activity of ERK and AMPK, and the function of islet beta-cells were observed to
      be improved in experimental mice treated with aerobic exercise. Furthermore,
      blood lipid metabolism and insulin resistance were improved by treatment with
      aerobic exercise. Body weight and glucose concentration of serology was markedly
      improved in mouse models of type-II diabetes mellitus. Furthermore, TLR-4
      inhibition markedly promoted ERK and AMPK expression levels and activity. Thus,
      these results indicate that aerobic exercise may improve blood lipid metabolism,
      insulin resistance and glucose plasma concentration in mouse models of type-II
      diabetes mellitus. Thus indicating aerobic exercise is beneficial for improvement
      of blood lipid and insulin resistance via the TLR-4-mediated ERK/AMPK signaling
      pathway in the progression of type-II diabetes mellitus.

PMID- 29658606
TI  - Chloroquine inhibits cell growth in human A549 lung cancer cells by blocking
      autophagy and inducing mitochondrial-mediated apoptosis.
AB  - Chloroquine (CQ) has been revealed to exhibit antitumor activity in several human
      tumors including lung cancer as mono- or add-on therapy. The antitumor effect of
      CQ appears to depend on the tumor type, stage and genetic context. Few studies
      have focused on the mechanism concerning the antitumor effect of CQ monotherapy
      and the cause and effect relationship among autophagy, apoptosis and CQ in human
      lung A549 cells. Therefore, the present study aimed to identify the antitumor
      effect of CQ monotherapy and analyze the possible mechanism. In the present
      study, we demonstrated that CQ suppressed human A549 cell growth in a dose- and
      time-dependent manner. CQ-mediated growth inhibition in A549 cells was
      characterized by the targeting of the PI3K/AKT pathway, thus, inducing
      mitochondria-mediated apoptosis at relatively higher concentrations by
      downregulating Bcl-2 expression, increasing the expression level of Bax,
      decreasing mitochondrial membrane potential, releasing cytochrome c from the
      mitochondria into the cytosol, activating caspase-3 and cleaving PARP.
      Collectively, these findings may offer a new rationale for using CQ as a lung
      cancer therapy drug in clinical practice.

PMID- 29658607
TI  - Key signaling pathways, genes and transcription factors associated with
      hepatocellular carcinoma.
AB  - The purpose of the present study was to investigate the underlying molecular
      mechanism of hepatocellular carcinoma (HCC) using bioinformatics approaches. The
      microarray dataset GSE64041 was downloaded from the Gene Expression Omnibus
      database, which included 60 tumor liver samples and 60 matched control samples.
      Differentially expressed genes (DEGs) between HCC and control groups were
      identified. Then functional enrichment analyses, protein-protein interaction
      (PPI) network, sub-network and integrated transcription factor (TF)-microRNA
      (miRNA)-target network analyses were performed for these DEGs. A total of 378
      DEGs were obtained, including 101 upregulated and 277 downregulated DEGs. In
      addition, functional enrichment analysis for DEGs in the sub-network revealed
      'cell division' and 'cell cycle' as key Gene Ontology (GO) terms and pathways.
      Topoisomerase (DNA) IIalpha (TOP2A) and integrin subunit alpha2 (ITGA2) were hub
      nodes in the PPI network. TOP2A, cyclin dependent kinase 1 (CDK1) and polo like
      kinase 1 (PLK1) were revealed to be hub nodes in the sub-network. Finally, 4 TFs
      including forkhead box M1 (FOXM1), E2F transcription factor 4 (E2F4), SIN3
      transcription regulator family member A (SIN3A) and transcription factor 7 like 1
      (TCF7L1) were obtained through integrated network analysis. TOP2A, ITGA2, PLK1
      and CDK1 may be key genes involved in HCC development. 'Cell division' and 'cell
      cycle' were indicated to act as key GO terms and Kyoto Encyclopedia of Genes and
      Genomes pathways in HCC. In addition, FOXM1, TCF7L1, E2F4 and SIN3A were revealed
      to be key TFs associated with HCC.

PMID- 29658608
TI  - IPSC-MSC inhibition assessment in Raw 264.7 cells following oxygen and glucose
      deprivation reveals a distinct function for cardiopulmonary resuscitation.
AB  - Hypoxia is a serious stress state. The nervous system is less tolerant to
      hypoxia, and cell death due to hypoxia is irreversible. With the incidence of
      cardiovascular disease gradually increasing, the sudden cardiac death rate is
      additionally increasing. Although cardiopulmonary resuscitation (CPR) is an
      important development, recovery is frequently poor. In a successful recovery
      population, ~40% of the population was in a vegetative state or subsequently
      succumbed to their condition, and ~20% had brain damage. Therefore, the recovery
      of the brain is of particular importance in CPR. Immune disorders are one of the
      major mechanisms of cerebral resuscitation following CPR. Studies have
      demonstrated that induced pluripotent stem cell-derived mesenchymal stem cells
      (IPSC-MSCs) have a strong immune regulatory effect during tissue repair and anti
      inflammatory effects. IPSC-MSCs may inhibit the inflammatory response by means of
      the inflammatory reaction network to improve brain function following CPR,
      although the cellular and molecular mechanisms remain unclear. Macrophages are a
      bridge between innate immune and specific immune responses in the body;
      therefore, it was hypothesized that macrophages may be the important effector
      cell of the role of IPSC-MSCs in improving brain function following recovery of
      spontaneous respiration and circulation subsequent to cardiopulmonary
      resuscitation. In the present study, IPSC-MSCs were applied to the oxygen and
      glucose deprivation (OGD) model. It was observed that intervention with IPSC-MSCs
      was able to alter the polarization direction of macrophages. The difference in
      the proportions of M1 and M2 macrophages was statistically significant at 6, 12,
      24 and 48 h (P=0.037, P<0.05) in the OGD + IPSC-MSCs group (M1, 33.48+/-5.6%; M2,
      50.84+/-6.9%) and in the OGD group (M1, 83.55+/-7.3%; M2, 11.41+/-3.2%), and over
      time this trend was more obvious. The polarization direction of macrophages is
      associated with the neurogenic locus notch homolog protein 1 (Notch-1) signaling
      pathway. In conclusion, it was observed that IPSC-MSCs may be associated with
      altered macrophage polarization, which may be accomplished by inhibiting the
      Notch-1 signaling pathway.

PMID- 29658610
TI  - Overexpression of IL-9 induced by STAT3 phosphorylation is mediated by miR-155
      and miR-21 in chronic lymphocytic leukemia.
AB  - Interleukin-9 (IL-9) can function as both a positive and negative regulator of
      immune response, however the role of IL-9 in tumor immunity is poorly understood.
      Chronic lymphocytic leukemia (CLL) is the most common chronic lympho
      proliferative disorder. Twenty CLL patients from 2010 to 2011 were recruited in
      the study. Expression and phosphorylation of transcription factor STAT3 and
      differential microRNAs (miRs) in peripheral blood mononuclear cells (PBMCs) from
      CLL patient samples were analyzed. In a previous study, we found a high level of
      IL-9 in CLL patients. Concomitantly, overexpression of pSTAT3, miR-155, and miR
      21 were observed in PBMCs from CLL patients in the present study. To elucidate
      whether there was interaction among IL-9, STAT3, miR-155, and miR-21, MEC-1 cells
      were used for further study. Our results revealed that there was no detectable IL
      9 in the culture medium of MEC-1 cells. However, the IL-9 protein could be
      detected using western blotting in MEC-1 cells. Notably, when recombinant human
      IL-9 (rIL-9) was added to the medium of culturing MEC-1 cells, the expression
      levels of pSTAT3 and IL-9 in MEC-1 cells were increased in a time-dependent
      manner, which could be blocked by STAT3 inhibitor. Both miR-155 and miR-21 could
      increase IL-9 expression, which could also be suppressed by the inhibitor of
      STAT3. Our data indicated that the existence of the novel 'extracellular IL
      9/pSTAT3/miR-155/miR-21/intracellular IL-9' positive feedback system in CLL
      cells, provides a novel insight in the pathogenesis and possible therapeutic
      strategy of CLL.

PMID- 29658609
TI  - Survivin knockdown induces senescence in TTF-1-expressing, KRAS-mutant lung
      adenocarcinomas.
AB  - Survivin plays a key role in regulating the cell cycle and apoptosis, and is
      highly expressed in the majority of malignant tumors. However, little is known
      about the roles of survivin in KRAS-mutant lung adenocarcinomas. In the present
      study, we examined 28 KRAS-mutant lung adenocarcinoma tissues and two KRAS-mutant
      lung adenocarcinoma cell lines, H358 and H441, in order to elucidate the
      potential of survivin as a therapeutic target. We found that 19 (68%) of the 28
      KRAS-mutant lung adenocarcinomas were differentiated tumors expressing thyroid
      transcription factor-1 (TTF-1) and E-cadherin. Patients with tumors
      immunohistochemically positive for survivin (n=18) had poorer outcomes than those
      with survivin-negative tumors (n=10). In the H358 and H441 cells, which expressed
      TTF-1 and E-cadherin, survivin knockdown alone induced senescence, not apoptosis.
      However, in monolayer culture, the H358 cells and H441 cells in which survivin
      was silenced, underwent significant apoptosis following combined treatment with
      ABT-263, a Bcl-2 inhibitor, and trametinib, a MEK inhibitor. Importantly, the
      triple combination of survivin knockdown with ABT-263 and trametinib treatment,
      clearly induced cell death in a three-dimensional cell culture model and in an in
      vivo tumor xenograft model. We also observed that the growth of the H358 and H441
      cells was slightly, yet significantly suppressed in vitro when TTF-1 was
      silenced. These findings collectively suggest that the triple combination of
      survivin knockdown with ABT-263 and trametinib treatment, may be a potential
      strategy for the treatment of KRAS-mutant lung adenocarcinoma. Furthermore, our
      findings indicate that the well-differentiated type of KRAS-mutant lung tumors
      depends, at least in part, on TTF-1 for growth.

PMID- 29658611
TI  - Effects of nicotine on the metabolism and gene expression profile of Sprague
      Dawley rat primary osteoblasts.
AB  - Smoking is a risk factor associated with bone and oral diseases, particularly
      periodontitis. Nicotine, the major toxic component of tobacco, is able to affect
      the quality and quantity of bone. Osteoblasts serve an important role in bone
      formation. Thus far, the effects of nicotine on metabolism-associated gene and
      protein expression in osteoblasts have been controversial and the mechanisms
      remain unclear. The present study assessed alterations in osteogenic activity by
      performing a Cell Counting kit-8 assay to investigate proliferation, Annexin V
      fluorescein isothiocyanate/propidium iodide staining to investigate apoptosis,
      alizarin red staining to investigate the formation of mineralized nodules,
      reverse transcription-quantitative polymerase chain reaction and western blotting
      to investigate the mRNA and protein levels of collagen I, alkaline phosphatase,
      bone osteocalcin, bone sialoprotein and osteopontin; and mRNA microarray
      expression analysis, Kyoto Encyclopedia of Genes and Genomes and Gene Ontology
      analysis to investigate the whole genome expression profile of Sprague-Dawley
      (SD) rat primary osteoblasts following treatment with different concentrations of
      nicotine. The results demonstrated that nicotine inhibited proliferation,
      promoted early apoptosis and inhibited mineralized nodule formation in a dose
      dependent manner by regulating alkaline phosphatase activity and the expression
      of osteoblast metabolism-associated genes and proteins. According to microarray
      analysis, several genes associated with bone metabolism and genes in the Hedgehog
      and Notch signaling pathways were downregulated significantly in nicotine-treated
      osteoblasts. The results of the present study indicated that nicotine may serve
      an inhibitory, dose-dependent role in SD rat primary osteoblasts that may be
      caused by the perturbation of genes and signaling pathways associated with bone
      formation. These results may provide a theoretical basis for future research
      regarding bone metabolism and targeted treatment of oral diseases associated with
      smoking.

PMID- 29658612
TI  - let-7d-3p is associated with apoptosis and response to neoadjuvant chemotherapy
      in ovarian cancer.
AB  - Altered expression of microRNAs contributes to the heterogeneous biological
      behavior of human malignancies and it may correlate with the clinical
      pathological features of patients. The let-7 microRNA family is frequently
      downregulated in human cancers and its aberrant expression may be a useful marker
      for prediction of the clinical response to therapy in patients. In the present
      study, we analyzed the expression of three members of the let-7 family (let-7a
      3p, let-7d-3p and let-7f), which remains largely uncharacterized in ovarian
      cancer tissues. We also investigated the function of let-7d-3p in the apoptosis
      and sensitization to chemotherapy in ovarian cancer cells. Our data from stem
      loop quantitative RT-PCR showed that expression of let-7a-3p and let-7d-3p, but
      not let-7f, was significantly (P<0.04) upregulated in ovarian tumors relative to
      that noted in normal ovarian tissues. Markedly, an increased expression of let-7d
      3p (also known as let-7d-3*) was associated with positive response to
      carboplatin/paclitaxel treatment in ovarian cancer patients. To investigate the
      biological relevance of let-7d-3p, we knocked down its expression in SKOV-3
      ovarian cancer cell line using antagomiRs. Loss of function analysis showed that
      inhibition of let-7d-3p significantly (P<0.05) impaired cell proliferation and
      activated apoptosis. In contrast, scratch/wound healing and Transwell chamber
      assays showed that migration and invasion abilities were not affected in the let
      7d-3p-deficient SKOV-3 cancer cells. Notably, Annexin V assays showed a
      significant (P<0.05) increase in cell death of cancer cells treated with the let
      7d-3p inhibitor plus carboplatin indicating a synergistic effect of the drug with
      antagomiR therapy. Gene ontology classification of predicted targets of let-7d-3p
      identified a number of genes involved in cellular pathways associated with
      therapy resistance such as ABC transporters, HIF-1, RAS and ErbB signaling. In
      summary, our findings showed that inhibition of let-7d-3 activates apoptosis and
      that its upregulation is associated with a positive response of ovarian cancer
      patients to carboplatin/paclitaxel chemotherapy.

PMID- 29658613
TI  - Detection of survivin expression in bladder cancer and renal cell carcinoma using
      specific monoclonal antibodies.
AB  - Survivin, which is highly expressed in the majority of tumors, but not in most
      normal adult tissues, has been identified to have significant clinical
      applications. In the present study, using survivin-specific monoclonal antibodies
      (mAbs), we aimed to establish methods for detecting the expression of survivin in
      cancer cell lines, serum samples, urine samples and cancer tissues from patients
      with bladder cancer (BCa) and renal cell carcinoma (RCC), and to evaluate the
      efficacy of survivin as a tumor marker in the surveillance of BCa and RCC. First,
      mAbs were labeled with horseradish peroxidase (HRP), and a sandwich enzyme-linked
      immunosorbent assay (ELISA) with mAbs and HRP-conjugated mAbs was developed to
      detect survivin expression in serum and urine samples from BCa and RCC patients,
      with samples from healthy controls (HCs) used for comparison. The HRP-conjugated
      mAbs were also used to detect survivin expression in cancer cell lines by western
      blotting. Survivin expression in cancer tissues from BCa patients was also
      evaluated by immunohistochemistry. The results showed that the sandwich ELISA was
      successfully established, and significantly higher expression of survivin was
      subsequently detected in BCa and RCC patients as compared with HCs in both
      urinary and serum samples (P<0.05), and was more pronounced in urine. The HRP
      mAbs could recognize survivin in cancer cell lines. Western blotting and
      immunohistochemistry results confirmed survivin expression in the 5637 BCa cell
      line, as well as BCa tissues. In addition, the expressions of survivin in BCa
      tissues, urine and serum were consistent in our study. In conclusion, the
      sandwich ELISA successfully established in the present study was of high
      sensitivity and specificity in the detection of survivin expression. The results
      also indicated that survivin is a potential tumor marker for the surveillance of
      BCa and RCC.

PMID- 29658614
TI  - Scaling up action on the prevention and control of noncommunicable diseases in
      the WHO Eastern Mediterranean Region.

PMID- 29658615
TI  - The integration and management of noncommunicable diseases in primary health
      care.

PMID- 29658616
TI  - Multiple tobacco use among young adult waterpipe smokers in Egypt.
AB  - Background: The use of multiple tobacco products is an emerging trend. Studies on
      multiple use among waterpipe smokers are limited. Objectives: We aimed to
      estimate the proportion of other tobacco products used by current adult waterpipe
      smokers in Egypt and identify the determinants of multiple tobacco product use.
      Methods: Population-based surveys were conducted using interview questionnaires
      during 2015-2017 in urban Cairo and rural Menoufia. Participants aged 18 years
      and older were selected using purposive quota non-random sampling. The total
      sample included 2 014 participants. We analysed the data on 1 490 current
      waterpipe smokers. Variables recorded included: tobacco use, health beliefs,
      waterpipe smoking behaviour, sociodemographic characteristics, and perceived
      effectiveness of pictorial health warnings on waterpipe tobacco packs. Current
      waterpipe smokers were classified as waterpipe-only users and multiple tobacco
      product users. Results: Almost half (47.9%) of the current waterpipe smokers used
      multiple tobacco products; 93.4% were dual users and 6.6% poly-users. The other
      tobacco products used were cigarettes (86.4%), electronic nicotine delivery
      systems (ENDS) (7.0%) or both (6.6%). Multiple users were more likely to be
      younger than waterpipe-only users. Young adult female waterpipe smokers used ENDS
      12 times more than young adult males (48.8% versus 4.1% respectively). Non-daily
      waterpipe smoking, usually smoking at cafes, higher education and knowledge of
      pictorial health warnings were independent predictors of multiple tobacco product
      use. Conclusion: Multiple tobacco product use was common among current waterpipe
      smokers in our study. Interventions to tackle non-cigarette and multiple tobacco
      use, especially in young adults, are urgently needed.

PMID- 29658617
TI  - Assessment of salt concentration in bread commonly consumed in the Eastern
      Mediterranean Region.
AB  - Background: Hypertension is the most important cardiovascular risk factor in the
      World Health Organization (WHO) Eastern Mediterranean Region. Excessive salt and
      sodium intake is directly related to hypertension, and its reduction is a
      priority of WHO. Bread is the leading staple food in the Region; therefore,
      reducing the amount of salt added to bread could be an effective measure for
      reducing salt intake. Aim: The study sought to determine the levels of sodium and
      salt in locally produced staple bread from 8 countries in the Region. Methods:
      Bread samples were collected randomly from bakeries located in the capital cities
      of the selected countries. The samples were analysed for sodium content using
      atomic absorption spectroscopy. Results: The mean salt content of breads varied
      from 4.28 g/kg in Jordan to 12.41 g/kg in Tunisia. The mean salt and sodium
      content in bread for all countries was 7.63 (SD 3.12) and 3.0 (SD 1.23) g/kg,
      respectively. The contribution of bread to daily salt intake varied considerably
      between countries, ranging from 1.3 g (12.5%) in Jordan to 3.7 g (33.5%) in
      Tunisia. Conclusion: Interventions to reduce population salt intake should target
      reduction of salt in bread in all countries. The amount of salt added to bread
      should be standardized and relevant legislation developed to guide bakers.
      Setting an upper limit for salt content in flat bread (pita or Arabic bread) at
      0.5% is strongly recommended. However, salt levels at <= 1% would be appropriate
      for other kind of breads.

PMID- 29658618
TI  - Implementation of the International Code of Marketing of Breastmilk Substitutes
      in the Eastern Mediterranean Region.
AB  - Background: Optimal breastfeeding practices and appropriate complementary feeding
      improve child health, survival and development. The countries of the Eastern
      Mediterranean Region have made significant strides in formulation and
      implementation of legislation to protect and promote breastfeeding based on The
      International Code of Marketing of Breast-milk Substitutes (the Code) and
      subsequent relevant World Health Assembly resolutions. Aim: To assess the
      implementation of the Code in the Region. Methods: Assessment was conducted by
      the World Health Organization (WHO) Regional Office for the Eastern Mediterranean
      using a WHO standard questionnaire. Results: Seventeen countries in the Region
      have enacted legislation to protect breastfeeding. Only 6 countries have
      comprehensive legislation or other legal measures reflecting all or most
      provisions of the Code; 4 countries have legal measures incorporating many
      provisions of the Code; 7 countries have legal measures that contain a few
      provisions of the Code; 4 countries are currently studying the issue; and only 1
      country has no measures in place. Further analysis of the legislation found that
      the text of articles in the laws fully reflected the Code articles in only 6
      countries. Conclusion: Most countries need to revisit and amend existing national
      legislation to implement fully the Code and relevant World Health Assembly
      resolutions, supported by systematic monitoring and reporting.

PMID- 29658619
TI  - Prevalence of risk factors for noncommunicable diseases in adults: key findings
      from the Pakistan STEPS survey.
AB  - Background: Pakistan lacks data on the prevalence of risk factors for common
      noncommunicable diseases (NCDs). Objectives: This study aimed to determine the
      prevalence of risk factors for NCDs among a population-based sample in Punjab and
      Sindh provinces, Pakistan. Methods: This study was conducted in 2013-2014. The
      NCD risk factors examined were: current daily smoking, eating fewer than 5
      servings of fruits/vegetable a day, low physical activity, overweight and
      obesity. A total of 7 710 households were selected and 1 adult was enrolled from
      each household. Data were collected using the WHO STEPS instrument (Step 1 and
      2), and analysed according to the STEPS statistical plan. Results: The prevalence
      of tobacco use was 19.7%. The majority of the respondents (96.5%) consumed fewer
      than 5 servings of fruits/vegetables a day, 41.5% had a low level of physical
      activity, 26.3% were overweight and 14.9% were obese. The prevalence of stage I
      and stage II hypertension, including those on medication, was 37% and 15.9%
      respectively. The prevalence of NCD risk factors differed significantly by sex
      and occupation (P = 0.0001) but not by age group (P = 0.118), level of education
      (P = 0.668) and province (P = 0.056). Only 0.6% of the sample had none of the 5
      NCD risk factors while 40% had 3-5. Conclusion: The high prevalence of NCD risk
      factors in Punjab and Sindh provinces is of concern. Urgent public health
      interventions are needed to reduce them, especially in youth and young adults.

PMID- 29658620
TI  - Impact of economic sanctions on access to noncommunicable diseases medicines in
      the Islamic Republic of Iran.
AB  - Background: It has been argued that economic sanctions and the economic crisis
      have adversely affected access to drugs. Aim: To assess the impact of economic
      sanctions on the Iranian banking system in 2011 and Central Bank in 2012 on
      access to and use of drugs for noncommunicable diseases (NCDs). Methods: An
      interrupted time series study assessed the effects of sanctions on drugs for
      diabetes (5 drug groups), asthma (5 drug groups), cancer (14 drugs) and multiple
      sclerosis (2 drugs). We extracted data from national reference databases on the
      list of drugs on the Iranian pharmaceutical market before 2011 for each selected
      NCD and their monthly sales. For cancer drugs, we used stratified random sampling
      by volume and value of sales, and source of supply (domestic or imported). Data
      were analysed monthly from 2008 to 2013. Results: Market availability of 13 of 26
      drugs was significantly reduced. Ten other drugs showed nonsignificant reductions
      in their market availability. Interferon alpha2b usage reduced from 0.014 defined
      daily doses per 1000 inhabitants per day (DID) in 2010 to 0.008 in 2013; and
      cytarabine from 1.40 mg per 1000 population per day in 2010 to 0.96 in 2013.
      Selective beta2-adrenoreceptor agonists usage reduced from 8.4 to 6.8 DID in the
      same time period. Conclusion: There is strong evidence that sanctions have had a
      negative effect on access to drugs, particularly those that depended on the
      import of their raw material or finished products.

PMID- 29658621
TI  - Scaling up prevention and control of noncommunicable diseases in the WHO Eastern
      Mediterranean Region.
AB  - Surveillance is an essential component in the campaign to prevent and control
      noncommunicable diseases (NCDs), both globally and in the Eastern Mediterranean
      Region (EMR). In order to address the increasing burden from these diseases,
      countries must first evaluate their own systems and see what steps need to be
      taken to improve preparedness. Therefore, the WHO Regional Office for the Eastern
      Mediterranean in Cairo, Egypt, conducts country capacity surveys on a regular
      basis to compare each Member State's NCD provision to the Framework for Action to
      implement the UN Political Declaration (2011). Ten progress indicators cover
      governance and planning, reducing risk factors and healthcare provision. Each one
      is scored for whether a country is fully, partially or not achieving this goal.
      This review focuses on comparing the Progress Monitor reports for the 22 EMR
      countries in 2015 and 2017. While the criteria used to assess some of the
      indicators have been updated over this period, many categories still show strong
      improvements. However, others still require extensive work if countries are to
      meet the sustainable development goal of reducing by 25% the number of premature
      deaths from NCDs by the year 2025.

PMID- 29658622
TI  - MPOWER, needs and challenges: trends in the implementation of the WHO FCTC in the
      Eastern Mediterranean Region.
AB  - Background: WHO MPOWER aims to help countries prioritize tobacco control measures
      in line with the WHO Framework Convention on Tobacco Control. Objectives: This
      paper assessed the progress and challenges in implementing the 6 priority
      policies of MPOWER in countries of the WHO Eastern Mediterranean Region since
      2011. Methods: A checklist was developed and scores assigned based on the MPOWER
      indicators (maximum score 37). MPOWER data for the Region in the 2015 and 2017
      tobacco control reports were extracted and scored. Data from similar analyses for
      2011 and 2013 were also included. Countries were ranked by scores for each
      indicator for 2015 and 2017 and for overall scores for 2011 to 2017. Results: The
      Islamic Republic of Iran, Egypt and Pakistan had the highest scores in 2015 (33,
      29 and 27 respectively) and the Islamic Republic of Iran, Pakistan and Yemen had
      the highest scores in 2017 (34, 31 and 27 respectively). The indicators with the
      highest and lowest combined score for all countries were for advertising bans and
      compliance with smoke-free policies: 67 and 18 respectively in 2015, and 73 and
      15 respectively in 2017. Most countries (15/22) had higher total scores in 2017
      than 2015: Afghanistan, Bahrain and Syrian Arab Republic had the greatest
      increases. The total score for the Region increased from 416 out of a maximum
      score of 814 in 2011 to 471 in 2017. Conclusions: Although notable achievements
      have been made in the Region, many challenges to policy implementation remain and
      require urgent action by governments of the countries of the Region.

PMID- 29658623
TI  - Tobacco advertising, promotion and sponsorship in entertainment media: a
      phenomenon requiring stronger controls in the Eastern Mediterranean Region.
AB  - Tobacco use and placement of tobacco products in television (TV) productions and
      movies is a way to promote tobacco use while avoiding tobacco advertising bans
      that exist in most countries. The fact that such productions are broadcast widely
      and viewed by millions, including children and young people, is of concern. This
      paper reviews the evidence on the use of tobacco advertising, promotion and
      sponsorship (TAPS) in TV and films in the Eastern Mediterranean Region and the
      ways to combat it. Evidence from Egypt shows considerable and increasing use of
      tobacco products by actors on screen, including female actors, in programmes
      aired during Ramadan in 2015-2017. A study of Iranian movies in 2015 showed that
      tobacco scenes in Iranian movies were increasing. In 2014, the WHO Regional
      Office for the Eastern Mediterranean held a consultative meeting on TAPS in
      drama. The consultation recommended regulating the tobacco presence in movies and
      TV through complete implementation of Article 13 of the WHO FCTC, and raising the
      issue to the WHO FCTC Conference of the Parties. In 2016, the Conference of the
      Parties called on parties to consider scaling up the implementation of WHO FCTC
      Article 13 and monitoring the use of TAPS in entertainment media in accordance
      with national legislation. A comprehensive approach is essential to end the
      tobacco industry's use of TV productions and movies to promote their products.

PMID- 29658624
TI  - Review of the nutrition situation in the Eastern Mediterranean Region.
AB  - This situation analysis for the World Health Organization Eastern Mediterranean
      Region focuses on specific nutrition indicators, namely low birth weight,
      exclusive breastfeeding, under- and overnutrition (anthropometric indicators) and
      anaemia. The regional average prevalence of low birth weight and exclusive
      breastfeeding was estimated at 19.31% and 29.3%, respectively. Stunting, wasting
      and underweight had an average prevalence of 28%, 8.69% and 18%, respectively.
      Afghanistan, Djibouti, Pakistan, Sudan and Yemen had the highest burden of
      stunting (> 30%). Prevalence of anaemia ranged from 7.4% to 88% in children aged
      < 5 years and from 19.9% to 63% in women of childbearing age. Of concern is the
      increasing trend in overweight and obesity among adults and children. Average
      prevalence of overweight and obesity was 27% and 24% in adults and 16.5% and 4.8%
      in school-aged children, respectively. The highest levels of obesity were
      reported from Bahrain, Kuwait, Qatar and the United Arab Emirates. This review
      highlights the double burden of malnutrition in countries of the Region and calls
      for the prioritization of policies aimed at improving the population's
      nutritional status.

PMID- 29658625
TI  - The development of the noncommunicable diseases emergency health kit.
AB  - The noncommunicable diseases (NCDs) emergency health kit was developed in
      response to the growing prevalence of NCDs in low and middle-income countries.
      Under conditions of conflict or following natural disasters, regular treatment of
      this category of diseases is often disrupted and rarely prioritized. This leads
      to greater morbidity and mortality both in the short and long term. The Eastern
      Mediterranean Region (EMR) has both a high incidence of NCDs and currently is the
      site of several major conflicts and hosts most of the world's refugees.
      Therefore, the WHO Regional Office for the Eastern Mediterranean initiated the
      development of the NCD emergency health kit to provide a structured set of
      medications, equipment and renewables to supply the needs of a population of 10
      000 people over a period of 3 months following disruption of normal medical
      services. This report discusses the rationale and anticipated use of the NCD
      emergency health kit followed by the selection criteria, structure, content and
      quantification process of the kit. Finally, the next steps are examined,
      including the procurement, logistics and monitoring and evaluation process of the
      kit.

PMID- 29658626
TI  - GABRIC Diabetes School: an innovative education centre for people with diabetes.
AB  - Diabetes prevalence and deaths attributable to diabetes continue to rise across
      globally. Diabetes Self-Management Education and Support (DSME/S) is a critical
      resource designed to help people with diabetes (PWD) successfully selfmanage
      their disease; however, its utilization is too low. In the Islamic Republic of
      Iran, there are currently limited structured educational programmes and no
      national standards for DSME/S protocol. In response to this, the GABRIC Diabetes
      Education Association (GDEA) has been developed as a school for diabetics, which
      has a comprehensive DSME/S programme for PWD with 18 distinct courses on 5 levels
      for 8 target groups. In addition, GABRIC has developed a database registry with
      more than 100 000 members throughout the country, of whom 95% are diabetic with a
      proportion of 82% Type 2 diabetes and 13% Type 1 diabetes. The success of the
      GABRIC school model results is yet to be investigated through study trials, and
      offers a fruitful line of research.

PMID- 29658627
TI  - Scaling up cancer care in the WHO Eastern Mediterranean Region.

PMID- 29658628
TI  - Workshop on WHO Framework Convention on Tobacco Control to promote the Protocol
      to eliminate illicit trade in tobacco products.

PMID- 29658629
TI  - Scaling up implementation of the United Nations Declaration on Prevention and
      Control of Noncommunicable Diseases.

PMID- 29658631
TI  - Royal Australasian College of Surgeons 87th Annual Scientific Congress Sydney,
      New South Wales, 7-11 May 2018.

PMID- 29658630
TI  - Lumbar sympathectomy versus prostanoids for critical limb ischaemia due to non
      reconstructable peripheral arterial disease.
AB  - BACKGROUND: Peripheral arterial disease (PAD) is a common circulatory problem
      that can lead to reduced blood flow to the limbs, which may result in critical
      limb ischaemia (CLI), a painful manifestation that occurs when a person is at
      rest. The mainstay of treatment for CLI is surgical or endovascular repair.
      However, when these means of treatment are not suitable, due to anatomical
      reasons or comorbidities, treatment for pain is limited. Lumbar sympathectomy and
      prostanoids have both been shown to reduce pain from CLI in people who suffer
      from non-reconstructable PAD, but there is currently insufficient evidence to
      determine if one treatment is superior. Due to the severity of the rest pain
      caused by CLI, and its impact on quality of life, it is important that people are
      receiving the best pain relief treatment available, therefore interest in this
      area of research is high. OBJECTIVES: To compare the efficacy of lumbar
      sympathectomy with prostanoid infusion in improving symptoms and function and
      avoiding amputation in people with critical limb ischaemia (CLI) due to non
      reconstructable peripheral arterial disease (PAD). SEARCH METHODS: The Cochrane
      Vascular Information Specialist (CIS) searched the Specialised Register (last
      searched 29 March 2017) and CENTRAL (2017, Issue 2). The CIS also searched
      clinical trials databases for ongoing or unpublished studies. SELECTION CRITERIA:
      Randomised controlled trials (RCTs), with parallel treatment groups, that
      compared lumbar sympathectomy (surgical or chemical) with prostanoids (any type
      and dosage) in people with CLI due to non-reconstructable PAD. DATA COLLECTION
      AND ANALYSIS: Three review authors independently selected trials, extracted data
      and assessed risk of bias. Any disagreements were resolved by discussion. We
      performed fixed-effect model meta-analyses, when there was no overt sign of
      heterogeneity, with risk ratios (RRs) and 95% confidence intervals (CIs). We
      graded the quality of evidence according to GRADE. MAIN RESULTS: We included a
      single study in this review comparing lumbar sympathectomy with prostanoids for
      the treatment of CLI in people with non-reconstructable PAD. The single study
      included 200 participants with Buerger's disease, a form of PAD, 100 in each
      treatment group, but only 162 were actually included in the analyses. The study
      compared an open surgical technique for lumbar sympathectomy with the prostanoid,
      iloprost, and followed participants for 24 weeks.Risk of bias was low for most
      evaluated domains. Due to the nature of the treatment, blinding of the
      participants and those providing the treatment would be impossible as a surgical
      procedure was compared with intravenous injections. It was not mentioned if
      blinded assessors evaluated the study outcomes, therefore, we judged subjective
      outcomes (i.e. pain reduction) to be at unclear risk of detection bias and
      objective outcomes (i.e. ulcer healing, amputation and mortality) at low risk of
      detection bias. We also rated the risk of attrition bias as unclear; 38 out of
      200 (19%) participants were not included in the analysis without clear
      explanation (16 of 100 in the iloprost arm and 22 of 100 in the sympathectomy
      arm). The quality of evidence was low due to serious imprecision because the
      study numbers were low and there was only one study included.The single included
      study reported on the outcome of complete healing without pain or major
      amputation, which fell under three separate outcomes for our review: relief of
      rest pain, complete ulcer healing and avoidance of major amputation. We chose to
      keep the outcome as a singularly reported outcome in order to not introduce bias
      into the outcomes, which may have been the case if reported separately. The
      limited evidence suggests participants who received prostaglandins had improved
      complete ulcer healing without rest pain or major amputation when compared with
      those who received lumbar sympathectomy (RR 1.63, 95% CI 1.30 to 2.05), but as it
      was the only included study, we rated the data as low-quality and could not draw
      any overall conclusions. The study authors stated that more participants who
      received prostaglandins reported adverse effects, such as headache, flushing,
      nausea and abdominal discomfort, but only one participant experienced severe
      enough adverse effects to drop out. Five participants who underwent lumbar
      sympathectomy reported minor wound infection (low-quality evidence). There was no
      reported mortality in either of the treatment groups (low-quality evidence).The
      included study did not report on claudication distances, quality of life or
      functional status, ankle brachial pressure index (ABPI), tissue oxygenation or
      toe pressures, or progression to minor amputation, complications or provide any
      cost-effectiveness data. AUTHORS' CONCLUSIONS: Low-quality evidence from a single
      study in a select group of participants (people with Buerger's disease) suggests
      that prostaglandins are superior to open surgical lumbar sympathectomy for
      complete ulcer healing without rest pain or major amputation, but possibly incur
      more adverse effects. Further studies are needed to better understand if
      prostaglandins truly are more efficacious than open surgical lumbar sympathectomy
      and if there are any concerns with adverse effects. It would be of great
      importance for future studies to include other forms of PAD (as Buerger's disease
      is a select type of PAD), other methods of sympathectomy as well as data on
      quality of life, complications and cost-effectiveness.

PMID- 29658632
TI  - Abstract Journal Rural Surgery.

PMID- 29658633
TI  - Abstract Journal Quality & Safety with Surgical Directors Program.

PMID- 29658634
TI  - Measurement of concentrations of four chemical ultraviolet filters in human
      breast tissue at serial locations across the breast.
AB  - The human population is widely exposed to benzophenone-3 (BP-3),
      octylmethoxycinnamate (OMC), 4-methylbenzilidenecamphor (4-MBC) and homosalate
      from their use in consumer goods to absorb ultraviolet (UV) light. Their
      oestrogenic activity and presence in human milk suggest a potential to influence
      breast cancer development. In this study, high-performance liquid chromatography
      tandem mass spectrometry was used to measure concentrations of these UV filters
      in human breast tissue from three serial locations across the breast from 40
      women undergoing mastectomy for primary breast cancer. One or more of these UV
      filters were quantifiable in 101 of 120 (84%) of the tissue samples and at least
      one breast region for 38 of 40 women. BP-3 was measured in 83 of 120 (69%) tissue
      samples and at least one breast region for 33 of 40 women (range 0-26.0 ng g-1
      tissue). OMC was measured in 89 of 120 (74%) tissue samples and at least one
      breast region for 33 of 40 women (range 0-58.7 ng g-1 tissue). 4-MBC was measured
      in 15 of 120 (13%) tissue samples and at least one breast region for seven of 40
      women (range 0-25.6 ng g-1 tissue). Homosalate was not detected in any sample.
      Spearman's analyses showed significant positive correlations between
      concentrations of BP-3 and OMC in each of the three breast regions. For ethical
      reasons cancerous tissue was not available, but as the location of the cancer was
      known, Mann-Whitney U-tests investigated any link between chemical concentration
      and whether a tumour was present in that region or not. For the lateral region,
      more BP-3 was measured when a tumour was present (P = .007) and for OMC the P
      value was .061. For seven (of 40) women with measurable 4-MBC, six of seven had
      measurable 4-MBC at the site of the tumour.

PMID- 29658635
TI  - Carlos L. Ballare.

PMID- 29658636
TI  - Taking the step: from Evo-Devo to plant-microbe interaction evolution with the
      liverwort Marchantia.

PMID- 29658637
TI  - Gaining a global perspective on Fagaceae genomic diversification and adaptation.

PMID- 29658638
TI  - Unravelling the mode of action of plant proteases.

PMID- 29658639
TI  - Endoscopic full-thickness resection for gastrointestinal submucosal tumors.
AB  - Endoscopic full-thickness resection (EFTR) is a "changing-concept" endoscopic
      resection technique, which safely allows resecting deep submucosal tumors (SMTs)
      in the gastrointestinal (GI) wall. It's a highly promising endoscopic procedure
      that allows full-thickness excision of a small piece of the complete GI wall by
      using only a flexible endoscope. EFTR is a meeting point between surgery and
      endoscopy and probably the onset of many prospective combined minimally invasive
      therapeutic techniques that science will explore. In this review, use of the EFTR
      technique for gastrointestinal SMTs is highlighted, focusing on some technical
      aspects, indications, contraindications and outcomes.

PMID- 29658640
TI  - Treatment for difficult bile duct stones: Balloon enteroscopy assisted-endoscopic
      retrograde cholangiopancreatography.

PMID- 29658641
TI  - Current strategies for the endoscopic management of difficult-to-treat bile duct
      stones in Japan.

PMID- 29658642
TI  - Endoscopic management of colorectal tumors less than 10 mm in size: Current
      status and future perspectives in Japan from a questionnaire survey.

PMID- 29658643
TI  - Laparoscopic endoscopic cooperative surgery for gastric cancer with severe
      fibrosis.

PMID- 29658644
TI  - Current status and future perspectives of endoscopic full-thickness resection.
AB  - Flexible endoscopy has developed from a diagnostic tool for tissue biopsy
      sampling to a treatment tool for endoscopic resection of neoplasms in the
      digestive tract. In the near future, one of the advanced endoscopic techniques,
      endoscopic full-thickness resection (EFTR), is expected to be a feasible
      endoscopic procedure. In the present review, systematic review of conventional
      exposed EFTR was carried out. Search queries were (endoscopic full-thickness
      resection or EFTR) (over-the-scope clip or OTSC) (Overstitch System) from 2015 to
      2017. Four retrospective, single-center studies with regard to conventional EFTR
      were identified. With regard to indication for conventional exposed EFTR,
      gastrointestinal stromal tumor was a good indication for EFTR. Mean tumor size of
      all four studies was 20.71 mm. In two studies, endoclips were used to close the
      resected opening without any complications, but the other two studies reported
      complications such as delayed perforation even using OTSC. Procedure times were
      reported from a minimum of 40 min to a maximum of 105 min. We also refer to
      introduction of a newly developed procedure of EFTR (non-exposed EFTR), and
      development of a new suturing device in Japan.

PMID- 29658645
TI  - Preface.

PMID- 29658646
TI  - Case of multiple cholesterol common bile duct stones that were refractory to
      endoscopic mechanical lithotripsy.

PMID- 29658647
TI  - Potential of artificial intelligence-assisted colonoscopy using an endocytoscope
      (with video).

PMID- 29658648
TI  - Current status and feasibility of endoscopic full-thickness resection in Japan:
      Results of a questionnaire survey.

PMID- 29658649
TI  - Challenges associated with the pathological diagnosis of colorectal tumors less
      than 10 mm in size.
AB  - Various techniques including cold snare polypectomy and endoscopic mucosal
      resection are used for the removal of small colorectal polyps. Specimens of
      resected polyps are prepared in pathology laboratories and analyzed to make a
      pathological diagnosis. However, reports on how different resection methods
      influence the pathological diagnosis are limited. This article discusses the
      problems associated with the failure of polyp retrieval and fragmentation of
      small specimens during collection and the effects of certain parameters on the
      pathological diagnosis, particularly with regard to surgical margins. In the
      future, although pathologists are expected to encounter problems as a result of
      minor findings that are not clinically problematic, relatively rare cases such as
      submucosal invasion by a small carcinoma should not be overlooked.

PMID- 29658650
TI  - Endoscopic management of bile duct stones in patients with surgically altered
      anatomy.
AB  - Bile duct stones in patients with surgically altered anatomy still pose a
      challenge to endoscopists. For successful endoscopic management of bile duct
      stones, there are multiple hurdles: Intubation to the afferent limb, biliary
      cannulation, ampullary intervention and stone extraction. The major advancement
      in this area is the development of dedicated device-assisted endoscopes for
      endoscopic retrograde cholangiopancreatography (ERCP). In patients with Billroth
      II reconstruction, a high technical success rate is reported using a duodenoscope
      but can be complicated by a potentially high perforation rate. In patients with
      Roux-en-Y reconstruction, device-assisted ERCP shows high technical success and
      low adverse event rates. Meanwhile, endoscopic papillary large balloon dilation
      enables safe and effective stone extraction with less use of endoscopic
      mechanical lithotripsy in patients with a dilated distal bile duct, but
      intraductal lithotripsy is sometimes necessary for management of very large bile
      duct stones. In cases with difficult stones, alternative approaches such as
      laparoscopy-assisted ERCP and endoscopic ultrasound (EUS)-guided intervention are
      increasingly reported with preliminary but promising results. However,
      comparative studies are still lacking in this area and prospective randomized
      controlled trials are warranted in terms of safety, efficacy and cost
      effectiveness.

PMID- 29658651
TI  - Peroral endoscopic submucosal tumor resection.

PMID- 29658652
TI  - Additional chromoendoscopy for colorectal lesions initially diagnosed with low
      confidence by magnifying narrow-band imaging: Can it improve diagnostic accuracy?
AB  - BACKGROUND AND AIM: Magnifying chromoendoscopy has been one of the most reliable
      diagnostic methods for distinguishing neoplastic from non-neoplastic lesions. The
      aim of this prospective study was to clarify the clinical usefulness of
      magnifying chromoendoscopy for colorectal polyps initially diagnosed with low
      confidence (LC) by magnifying narrow-band imaging (NBI). METHODS: Consecutive
      adult patients who underwent total colonoscopic examination with magnifying NBI
      between July and December 2016 at Sano Hospital were prospectively recruited.
      Endoscopists were asked to carry out additional magnifying chromoendoscopy for
      cases that had been initially diagnosed as Japan NBI Expert Team (JNET) Type 1 or
      2A with LC by magnifying NBI. We investigated the diagnostic performance of
      magnifying NBI for polyps diagnosed as JNET Type 1 or 2A with LC (first phase)
      and that of subsequent magnifying chromoendoscopy (second phase) in
      differentiating neoplasia from non-neoplasia. RESULTS: In 50 patients, we
      analyzed 53 polyps classified as JNET Type 1 or 2A with LC prediction. Accuracy
      and negative predictive value of magnifying NBI (first phase) were 58.5% (95% CI,
      44.1-71.9%) and 66.0% (95% CI, 36.6-77.9%), and those of magnifying
      chromoendoscopy (second phase) were 66.0% (95% CI, 51.7-78.5%) and 61.1% (95% CI,
      43.5-76.9%), respectively. CONCLUSION: Regardless of the findings of additional
      chromoendoscopy, all polyps should be resected and submitted for
      histopathological examination when the confidence level in differentiating
      adenomatous from hyperplastic polyps by magnifying NBI is low.

PMID- 29658653
TI  - Endoscopic excavation technique for gastric gastrointestinal stromal tumor: A
      case report.

PMID- 29658654
TI  - Cold snare polypectomy technique is a procedure with a low bleeding risk.

PMID- 29658655
TI  - Current endoscopic strategies for managing large bile duct stones.
AB  - Common bile duct stones are a relatively common occurrence and can often lead to
      devastating complications. Endoscopic retrograde cholangiopancreatography was
      introduced in the 1970s for management of common bile duct stones. Most common
      bile duct stones can be removed with simple techniques such as endoscopic
      sphincterotomy and balloon trawling. However, large bile duct stones continue to
      pose some difficulty in achieving complete extraction. In this article, we will
      review some of the established techniques such as the use of endoscopic papillary
      large balloon dilatation, mechanical lithotripsy, and cholangioscopy-assisted
      techniques. We will look at the recent literature to help clarify the particular
      methods and answer some of the questions surrounding these methods.

PMID- 29658656
TI  - Comparison between endoscopic and laparoscopic removal of gastric submucosal
      tumor.
AB  - BACKGROUND AND AIM: A retrospective study was conducted to compare two resection
      methods, namely, endoscopic resection (ER) procedures (endoscopic submucosal
      dissection [ESD], endoscopic muscularis dissection [EMD], and endoscopic full
      thickness resection [EFTR]) and laparoscopic resections (LR) (laparoscopic
      endoscopic cooperative surgery [LECS] and laparoscopic wedge resection). METHODS:
      Seventy-three patients who underwent ER (N = 33: ESD, N = 4; EMD, N = 15; EFTR, N
      = 14) or LR (N = 39: LECS, N = 16; wedge resection, N = 23) for gastric
      submucosal tumor (G-SMT) smaller than 50 mm were included in this study.
      Patient/tumor characteristics and intra/postoperative factors were compared
      between the ER and LR groups. RESULTS: The ER group had a significantly higher
      percentage of intraluminal growing type of tumor (100% vs 41%) and smaller tumor
      size (23 vs 33 mm) than the LR group. The ER group had a significantly shorter
      operative time (93 vs 145 min) and less blood loss (13 vs 30 mL) than the LR
      group. In the ER group, three patients who had tumors located on the anterior
      wall of the stomach required laparoscopic closure after EFTR because of
      difficulty in endoscopic closure of the gastric-wall defect. Postoperative
      complication rates and duration of postoperative hospital stays did not differ
      between the two groups. CONCLUSIONS: ER may be technically feasible, safe, less
      invasive, and oncologically appropriate options for selected patients with the
      intraluminal growing type of G-SMT smaller than 30 mm. EFTR may be more
      reasonable alternatives to LR in selected patients with a small G-SMT located on
      the lesser curvature side.

PMID- 29658657
TI  - Endoscopic ultrasonography-guided antegrade treatment for bile duct stone with
      multi-step approach in a patient with surgically altered anatomy.

PMID- 29658658
TI  - [Icaritin promotes maturation and mineralization of mouse osteoblast MC3T3-E1
      cells through CXCR4/SDF-1 signal pathway].
AB  - <b>Objective:</b> To investigate the effect of icaritin on maturation and
      mineralization of mouse osteoblast MC3T3-E1 cells and its mechanism.
      <b>Methods:</b> The cultured MC3T3-E1 cells were divided into blank control
      group, CXC chemokine receptor type 4 (CXCR4) inhibitor (AMD3100) group, icaritin
      group, and icaritin plus AMD3100 group. The expression of CXCR4, stromal cell
      derived factor 1 (SDF-1) and osteogenesis-related genes and proteins were
      detected by real-time RT-PCR and Western blotting after drug treatment for 24 h.
      The alkaline phosphatase (ALP) activity was determined with ALP kit on d3 and d6;
      calcium nodules were detected by alizarin red staining after drug treatment for
      14 d. <b>Results:</b> Real time RT-PCR showed that compared with the blank
      control group, relative expressions of <i>CXCR4, SDF-1</i> and osteogenesis
      related genes in icaritin group were significantly increased (<i>P</i><0.05 or
      <i>P</i><0.01); After AMD3100 treatment, the relative expression of <i>CXCR4</i>
      gene was decreased (<i>P</i><0.05). Western blot showed that compared with the
      blank control group, relative expressions of CXCR4, SDF-1 and osteogenesis
      related proteins in the icaritin group were significantly increased (all
      <i>P</i><0.01), but were decreased after AMD3100 was added (all <i>P</i><0.01).
      The ALP activity of icaritin group was significantly higher than that of blank
      control group (all <i>P</i><0.01) on d3 and d6 after drug treatment, while the
      activity of ALP was significantly decreased after AMD3100 treatment (all
      <i>P</i><0.01). At d14 after drug treatment, compared with the blank control
      group, the area of alizarin red staining was increased in the icaritin group,
      while it was significantly reduced after the addition of AMD3100.
      <b>Conclusion:</b> Icaritin may promote maturation and mineralization of mouse
      osteoblast MC3T3-E1 cells through CXCR4/SDF-1 signaling pathway.

PMID- 29658659
TI  - [Effect of resveratrol on peak bone mass in growing rats].
AB  - <b>Objective:</b> To investigate the effect of resveratrol on peak bone mineral
      density and bone mass in growing rats. <b>Methods:</b> Thirty-six female healthy
      Wistar rats were randomly divided into control group, icariin group and
      resveratrol group with 12 rats in each group. Icariin (25 mg.kg<sup>
      1</sup>.d<sup>-1</sup>), resveratrol (8.4 mg.kg<sup>-1</sup>.d<sup>-1</sup>) or
      equal volume of distilled water were given by gavage to icariin group,
      resveratrol group and control group, respectively. The rats were sacrificed after
      12 weeks. The organ indexes were calculated and pathology sections were observed;
      the bone mineral density (BMD), bone biomechanics, serum bone metabolism index,
      and results of micro-CT scan were analyzed. <b>Results:</b> During the
      experiment, the body weight of rats showed an increasing trend and there was no
      significant difference among three groups (<i>P</i>>0.05). There were no
      significant differences in organ index of vital organs and pathological changes
      among the groups (all <i>P</i>>0.05). Compared with the control group, the whole
      body BMD, and the BMDs of femur and vertebrae in icariin and resveratrol groups
      were significantly increased after 12 weeks (all <i>P</i><0.05). The maximum load
      values of femur and vertebrae, as well as elastic modulus of vertebrae in icariin
      and resveratrol groups were significantly higher than those in control group
      (<i>P</i><0.05 or <i>P</i><0.01). Micro-CT scan showed that the volumetric BMD,
      number of trabecular, trabecular thickness and bone volume/tissue volume of the
      cancellous bone in icariin and resveratrol groups were significantly higher and
      the trabecular separation was significantly lower than those in the control group
      (<i>P</i><0.05 or <i>P</i><0.01); while there was no significant difference in
      volumetric BMD of cortical bone for femur. The contents of osteocalcin in icariin
      and resveratrol groups were significantly higher than those in control group (all
      <i>P</i><0.05), while the contents of tartarte-resistant acid phosphatase 5b
      (TRACP5b) were significantly lower than those in control group (all
      <i>P</i><0.05).<b>Conclusion:</b> Resveratrol can inhibit bone resorption and
      enhance bone formation, so as to improve the peak bone mass and bone density,
      enhance bone strength and improve the microstructure of bone tissue in young
      rats.

PMID- 29658660
TI  - [Effect of low frequency low intensity electromagnetic fields on maturation and
      mineralization of rat skull osteoblasts <i>in vitro</i>].
AB  - <b>Objective:</b> To compare the effects of 50 Hz 1.8 mT sinusoidal magnetic
      field (SEMF) and 50 Hz 0.6 mT pulsed electromagnetic field(PEMF) on the
      maturation and mineralization of rat calvaria osteoblasts. <b>Methods:</b>
      Primary cultured rat calvarial osteoblasts were divided into 3 groups:blank
      control group, SEMF group and PEMF group. The rats in SEMT and PEMT groups were
      treated with 50 Hz 1.8 mT SEMF or 50 Hz 0.6 mT PEMF for 90 min/d, respectively.
      Western blotting and Real-time RT-PCR were used to detect the protein and mRNA
      expressions of Collagen-1, bone morphogenetic protein 2 (BMP-2), osterix (OSX)
      and Runt-associated transcription factor 2(Runx-2). The alkaline phosphatase(ALP)
      activity was detected by ALP test kits at d6 and d9 after treatment, and by ALP
      staining using azo coupling at d10 after treatment. The formation of calcium
      nodules was observed by alizarin red staining. <b>Results:</b> Compared with
      blank control group, the protein and mRNA expressions of Collagen-1, BMP-2, OSX
      and Runx-2 in SEMT and PEMT groups were significantly increased (<i>P</i> <0.01
      or <i>P</i> <0.05); while the mRNA expressions of Collagen-1 and BMP-2 in PEMF
      group were significantly higher than those in SEMF group. After 6 days treatment,
      the activity of ALP in PEMF group was significantly higher than that in blank
      control group (<i>P</i><0.05), while such difference was not observed in SEMF
      group (<i>P</i>>0.05); after 9 days treatment, the activities of ALP in both PEMF
      and SEMP groups were significantly higher than that in blank control group (all
      <i>P</i><0.05), but the difference between PEMF and SEMF groups was not
      significant (<i>P</i>>0.05). After 10 days treatment, ALP staining was increased
      in both PEMF and SEMF groups compared with that in blank control group (all
      <i>P</i><0.01), and the stained area was bigger in PEMF group than that in SEMF
      group (<i>P</i><0.05). After 12 days treatment, calcium nodules were increased in
      PEMF and SEMF groups compared with that in blank control group (all
      <i>P</i><0.01), and more calcium nodules were observed in PEMF group than SEMF
      group (<i>P</i><0.05). <b>Conclusion:</b> Both 50 Hz 1.8 mT that in SEMF and 50
      Hz 0.6 mT PEMF can promote the maturation and mineralization of osteoblasts, and
      the effect of PEMF is more marked.

PMID- 29658661
TI  - [Biomechanical and biocompatible enhancement of reinforced calcium phosphate
      cement via RGD peptide grafted chitosan nanofibers].
AB  - <b>Objective:</b> To analysis the biomechanical and biocompatible properties of
      calcium phosphate cement (CPC) enhanced by chitosan short nanofibers(CSNF) and
      Arg-Gly-Asp (RGD). <b>Methods:</b> Chitosan nanofibers were prepared by
      electrospinning, and cut into short fibers by high speed dispersion. CPC with
      calcium phosphorus ratio of 1.5:1 was prepared by Biocement D method. The
      composition and structure of CPC, CSNF, RGD modified CSNF (CSNF-RGD), CSNF
      enhanced CPC (CPC-CSNF), RGD modified CPC-CSNF (CPC-CSNF-RGD) were observed by
      infrared spectrum, X-ray diffraction (XRD) and scan electron microscopy (SEM).
      The mechanical properties were measured by universal mechanical testing
      instrument. The adhesion and proliferation of MC3T3 cells were assessed using
      immunofluorescence staining and MTT method. <b>Results:</b> The distribution of
      CSNF in the scaffold was homogeneous, and the porous structure between the
      nanofibers was observed by SEM. The infrared spectrum showed the characteristic
      peaks at 1633 nm and 1585 nm, indicating that RGD was successfully grafted on
      chitosan nanofibers. The XRD pattern showed that the bone cement had a certain
      curability. The stain-stress test showed that break strengths were (17.74+/-0.54)
      MPa for CPC-CSNF and (16.67+/-0.56) MPa for CPCP-CSNF-RGD, both were higher than
      that of CPC(all <i>P</i><0.05). The immunofluorescence staining and MTT results
      indicated that MC3T3 cells grew better on CPC-CSNF-RGD after 240 min of
      culture(all <i>P</i><0.05). <b>Conclusion:</b> CSNF-RGD can improve the
      biomechanical property and biocompatibility of CPC, indicating its potential
      application in bone tissue repair.

PMID- 29658662
TI  - [Application of mechanically reinforced 45S5 Bioglass<sup>(r)</sup>-derived
      bioactive glass-ceramic porous scaffolds for bone defect repairing in rabbits].
AB  - <b>Objective:</b> To evaluate the application of mechanically reinforced 45S5
      Bioglass<sup>(r)</sup>-derived glass ceramic porous scaffolds for repair of bone
      defect in rabbits. <b>Methods:</b> The BG-ZnB powders were added into the 45S5
      Bioglass<sup>(r)</sup> powder/paraffin microsphere mixtures and were sintered at
      900C to obtain porous scaffolds with highly bioactive BG-ZnB of 0%, 2% or 4% of
      mass fraction (denoted as 45S5/ZnB0, 45S5/ZnB2, 45S5/ZnB4). Phase composition,
      porosity and compression properties of three kinds of as-sintered scaffolds were
      characterized by X-ray analysis, mercury porosimetry, and mechanical test. Thirty
      six male New Zealand rabbits with critical-sized femoral bone defects were
      randomly divided into three groups (45S5/ZnB0 group, 45S5/ZnB2 group and
      45S5/ZnB4 group, 12 for each), and were implanted with three kinds of porous
      scaffolds respectively. X-ray, micro-CT three-dimensional reconstruction and
      tissue slice staining were used to detected the efficiency of bone regeneration
      at 6 and 16 weeks after operation. The growth of newly formed bone was observed
      using HE, Masson staining and EnVision method. <b>Results:</b> Phase compositions
      of 45S5/ZnB2 and 45S5/ZnB4 were the same with 45S5/ZnB0, but the average pore
      size and porosity of the scaffolds were decreased with the increase of BG-ZnB
      content. 45S5/ZnB2 and 45S5/ZnB4 scaffolds exhibited higher compressive strength,
      osteogenesis and trabecular density than those of the 45S5/ZnB0 scaffold (all
      <i>P</i><0.05). With the mechanical reinforcement of BG-ZnB increased, the
      content of new bone, collagen type I and osteocalcin increased.
      <b>Conclusion:</b> Low-melt BG-ZnB-assisted sintering is a promising approach to
      improve the mechanical strength of 45S5 Bioglass<sup>(r)</sup>.

PMID- 29658663
TI  - [microRNA-222 regulates proliferation and apoptosis of fibroblasts in
      hypertrophic scar via matrix metalloproteinase 1].
AB  - <b>Objective:</b> To explore the effect of microRNA(miR)-222 on cell
      proliferation and apoptosis of fibroblasts in hypertrophic scar (HS) and the
      underlying mechanisms. <b>Methods:</b> The expression of miR-222 in the HS and
      the normal skin tissues was detected by real-time RT-PCR. The HS fibroblasts were
      transfected with miR-222 mimic and miR-222 inhibitor respectively. The cell
      viability was tested with MTT assay, cell cycle distribution and apoptosis were
      detected with flow cytometry and the expression levels of proliferation,
      apoptosis and cell cycle related proteins were determined with Western blot.
      Direct target of miR-222 was evaluated by dual-luciferase reporter assay.
      <b>Results:</b> miR-222 was significantly up-regulated in HS tissues compared
      with normal skin tissues(<i>P</i><0.05). Overexpression of miR-222 enhanced the
      cell viability of HS fibroblasts; increased mRNA and protein expressions of
      proliferating cell nuclear antigen (PCNA), collagen alpha-1 (I) chain (Col1A1)
      and collagen alpha-1 (III) chain (Col3A1); increased cell population in S phase
      and protein expressions of cyclin D1, cyclin E1 and cyclin-dependent kinases 1
      (CDK1); inhibited cell apoptosis and reduced protein expressions of caspase-3/9.
      Overexpression of MMP1 attenuated the effects of miR-222 on the cell viability
      and apoptosis in fibroblasts, reduced expression levels of PCNA, cyclin D1 and
      the expression of caspase-3 was increased. <b>Conclusion:</b> miR-222 enhances
      cell proliferation and inhibits cell apoptosis of HS fibroblasts through negative
      regulation of MMP1, which suggests that miR-222 and MMP1 might be used as novel
      biomarkers and targets in diagnostic and therapeutic approaches for HS.

PMID- 29658664
TI  - [Primary cilium acts as an oxygen sensor in PC12 cells].
AB  - <b>Objective:</b> To investigate the function of primary cilium as an oxygen
      sensor in PC12 cells. <b>Methods:</b> The PC12 cells were transfected with IFT88
      siRNA. The nuclear translocation of hypoxia inducible factor-1alpha (HIF-1alpha),
      nuclear factor erythroid-2 related factor 2 (Nrf2), and ciliogenesis were
      observed by immunofluorescence staining; and the mRNA expressions of <i>HIF
      1alpha, Nrf2</i>, vascular endothelial growth factor (<i>VEGF</i>) and superoxide
      dismutase (<i>SOD</i>) were detected by real-time RT-PCR. <b>Results:</b> The
      ciliogenesis was inhibited in PC12 cells transfected with IFT88 siRNA. In hypoxia
      group and scramble control group, nuclear translocations of HIF-1alpha and Nrf2
      were observed and mRNA expressions of <i>HIF-1alpha, Nrf2, VEGF</i> were
      increased, and those of <i>SOD</i> were decreased. While in PC12 cells
      transfected with IFT88 siRNA, nuclear translocations of HIF-1alpha and Nrf2 were
      not observed, and mRNA expressions of <i>HIF-1alpha, Nrf2, VEGF</i> were
      inhibited, and mRNA expression of <i>SOD</i> was increased. <b>Conclusion:</b>
      Primary cilia may act as an oxygen sensor to transfer the information related to
      hypoxia and oxidative stress into cells, activating intracellular defense
      mechanism against the hypoxic injuries.

PMID- 29658665
TI  - [Application of enhanced recovery program in laparoscopic distal pancreatectomy].
AB  - <b>Objective:</b> To evaluate the feasibility and safety of applying enhanced
      recovery after surgery (ERAS) protocol in patients undergoing laparoscopic distal
      pancreatectomy. <b>Methods:</b> Data of 36 patients undergoing laparoscopic
      distal pancreatectomy from May 2016 to May 2017 in the First Affiliated Hospital,
      Zhejiang University School of Medicine were reviewed. The patients were divided
      into ERAS group (<i>n</i>=12) and control group (<i>n</i>=24). The patients in
      ERAS group received a series of enhanced recovery procedures, including
      multimodal analgesia, early off-bed activity and early oral food-taking, etc.
      Operation time, intraoperative blood loss, time to first flatus, postoperative
      complications, and length of postoperative hospital stay were evaluated.
      <b>Results:</b> There were no statistically significant differences in operation
      time and intraoperative blood loss between ERAS group and control group (all
      <i>P</i>>0.05). The time to first flatus and length of postoperative hospital
      stay were significantly shortened in ERAS group (all <i>P</i><0.05). The ERAS
      group had lower incidence of postoperative complications (41.7% vs. 66.7%), and
      the complications in ERAS group tended to be milder, but the differences failed
      to show statistical significance (all <i>P</i>>0.05). <b>Conclusion:</b> The ERAS
      protocol for laparoscopic distal pancreatectomy can significantly promote
      gastrointestinal function recovery and shorten postoperative hospital stay, and
      may reduce the incidence of postoperative complications.

PMID- 29658666
TI  - [Application of modified lateral window for maxillary sinus floor augmentation].
AB  - <b>Objective:</b> To evaluate the clinical efficacy of modified lateral window
      for maxillary sinus floor augmentation (MSFA). <b>Methods:</b> Fifty-five
      patients who visited the Stomatology Hospital Affiliated to Zhejiang University
      School of Medicine between June 2012 and October 2014 were enrolled in the study.
      Patients underwent MSFA with Bio-Oss grafts based on modified access window.
      During the operation the vertical height of the bony window was reduced from 6-8
      mm of conventional oval window to 4-5 mm of slot-shaped window. The sinus
      membrane was detached completely via the lateral access and large particle Bio
      Oss graft was placed in the sub-mucosal space. The implant survival, graft
      height, graft volume and resorption rates were measured. Intra-op and post-op
      complications were recorded. <b>Results:</b> There were 86 implants inserted. The
      2-4 year cumulative survival rates were 97.67% by implant-based analysis and
      96.36% by patient-based analysis. The residual bone height was (4.7+/-2.6) mm and
      bone width was (8.4+/-2.7) mm. The bone height of implantation site immediately
      after operation was (16.1+/-2.5) mm and it was (16.2+/-2.2) mm at restoration.
      The bone heights at 1 and 2 years after operation were (14.9+/-2.5) mm and
      (13.6+/-2.6) mm, respectively. The graft height was (10.6+/-2.8) mm and the graft
      volume was (1569+/-745) mm<sup>3</sup> immediately after operation. The
      resorption rate of graft height 6 months after operation was 3.79% and that of
      graft volume was 7.87%. The 1-year accumulative resorption rate of graft height
      was 6.63% and that of graft volume was 10.89%. The 2-year accumulative resorption
      rate of graft height was 7.58% and that of graft volume was 15.26%. Small
      membrane perforation during MSFA was observed in 5 cases and all were
      successfully repaired by a collagen Bio-Gide membrane. <b>Conclusion:</b> The
      modified lateral technique obtains high implant survival rate, excellent graft
      stability and low complication rate at 2-4 year clinical follow-up, indicating
      that it is a safe, predictable and minimally invasive surgical method for severe
      atrophic maxillary posterior dentition.

PMID- 29658667
TI  - [Endoscopic trans-fistula drainage for gastroesophageal anastomotic fistula with
      para-fistula abscess after esophagectomy].
AB  - <b>Objective:</b> To evaluate the efficiency and safety of endoscopic trans
      fistula drainage (ETFD) for gastroesophageal anastomotic fistula with para
      fistula abscess after esophagectomy. <b>Methods:</b> Among 456 esophageal cancer
      patients receiving esophagectomy between February 2012 and February 2017 in Sir
      Run Run Shaw Hospital, 15 cases were diagnosed as gastroesophageal anastomotic
      fistula with para-fistula abscess after surgery. Seven cases received ETFD
      treatment (ETFD group), and 8 cases received conventional treatment (control
      group). Recovery of inflammatory markers and fistula, length of hospital stay
      after esophagectomy and total medical expenses were compared between ETFD group
      and control group. <b>Results:</b> All patients recovered in ETFD group. Time of
      white cell count returning to normal and decline of C-reactive protein, time of
      fistula healing and length of hospital stay after esophagectomy in ETFD group
      were significantly shorter than those of control group (all <i>P</i><0.05). And
      medical expenses in ETFD group was also lower (<i>P</i><0.05). <b>Conclusion:</b>
      ETFD is effective and safe for gastroesophageal anastomotic fistula with para
      fistula abscess after esophagectomy.

PMID- 29658668
TI  - [Effect of Arg188Gln (G/A) mutation on enzymatic activity of kynureninase].
AB  - <b>Objective:</b> To verify whether the enzymatic activity of kynureninase (KYNU)
      could be changed by the Arg188Gln (G/A) mutation. <b>Methods:</b> The total RNA
      of human hepatic tissue was extracted and the <i>KYNU</i> gene cDNA was amplified
      by RT-PCR. Primers were designed according to the sequences around the site
      Arg188Gln of <i>KYNU</i> gene and the Arg188Gln (G/A) mutant <i>KYNU</i> cDNA was
      generated by site-directed mutagenesis. Both the wild-type and mutant-type
      <i>KYNU</i> genes were subcloned into pcDNA vectors and the recombinant plasmids
      were constructed. After being transfected into human embryonic kidney 293
      (HEK293) cells, the expression of KYNU recombinant plasmids were assessed by
      Western blot. The enzymatic activities of KYNU were detected by high performance
      liquid chromatography (HPLC). <b>Results:</b> The KYNU enzyme activities were
      expressed in both wild and mutant HEK293 cells. Michaelis constants (Km) of the
      wild and mutant KYNU were (9.833+/-0.513) MUmol/L and (29.900+/-0.265) MUmol/L,
      respectively (<i>P</i><0.05). The maximum velocities (Vmax) of the wild and
      mutant KYNU were (0.700+/-0.096) nmol.mg<sup>-1</sup>.min<sup>-1</sup> and
      (0.084+/-0.003) nmol.mg<sup>-1</sup>.min<sup>-1</sup>, respectively
      (<i>P</i><0.05). <b>Conclusion:</b> Arg188Gln (G/A) mutation can decrease the
      enzymatic activity of KYNU.

PMID- 29658669
TI  - [Segmented biodegradable esophageal stents in a porcine model: preclinical
      evaluation of degradation, complications and tissue reactions].
AB  - <b>Objective:</b> To evaluate the feasibility of two types of segmented
      biodegradable esophageal stents in treatment of refractory benign esophagus
      strictures. <b>Methods:</b> Uncovered biodegradable segmented stent and fully
      covered biodegradable segmented stent were implanted into the porcine esophagus
      (6 for each). Data on biodegradation, complications, and tissue reactions were
      compared between two groups. <b>Results:</b> All animals kept good general
      conditions; no death, decreased food intake, weight loss and malnutrition were
      observed. No perforation, ulcer, hemorrhage, stent migration and severe
      complications occurred. Stents degradation commenced at week 3. Stents structure
      breakage and complete stents absorption occurred at week 7-8 and week 9-10 in
      uncovered stents. While in fully-covered stents, stents structure breakage and
      complete stents absorption occurred at week 8-9 and week 10-11. Hyperplasia was
      prominent at week 1-3 and ameliorated at week 6 after stent implantation. A
      longer degradation period was present in fully-covered stents than in uncovered
      stents, while fully-covered stents induced tissue reactions at early stage were
      mild. <b>Conclusions:</b> The application of biodegradable esophageal stents with
      a segmented trunk in refractory benign esophagus strictures worth further
      investigation. The fully-covered stent has longer degradation period, which may
      be more suitable for clinical use.

PMID- 29658670
TI  - [Effect of exogenous L-arginie on survival of extended dorsal perforator flaps in
      rats].
AB  - <b>Objective:</b> To investigate the effect of exogenous L-Arg on the survival of
      extended perforator flap in rats. <b>Methods:</b> Sixteen male Sprague Dawley
      rats were randomly divided into L-Arg group (<i>n</i>=8) and control
      group(<i>n</i>=8). The extended dorsal three-vascular territory perforator flaps
      were made in rats. L-Arg (400 mg.kg<sup>-1</sup>.d<sup>-1</sup>) was injected
      intraperitoneally in L-Arg group 1d before operation, immediately and 1-7 d after
      operation, while the same volume of saline was injected intraperitoneally in
      control group at the same time points. The appearance and distribution of blood
      vessels were observed, and the flap survival areas were measured 7d after
      operation. The tissue samples were harvested from choke zone II for histological
      study and the expression of vascular endothelial growth factor (VEGF) was
      detected by immunohistochemistry and Western blot, respectively. <b>Results:</b>
      After 7d, the clearer vascular structure and more new vessels in choke zone II
      were observed in L-Arg group. The survival rate of flap in L-Arg group was
      (88.42+/-4.19)%, which was significantly higher than that in control
      group[(76.52+/-5.37)%, <i>t</i>=3.707, <i>P</i><0.01]. The microvessel density
      and caliber of choke zone II in L-Arg group was (29.47+/-5.28)/mm<sup>2</sup>
      and(47.27+/-5.32)MUm, which were significantly higher than those in control group
      (t=2.694 and 2.389, <i>P</i><0.05 or <i>P</i><0.01). The immunohistochemistry and
      Western blot showed that the expression of VEGF in choke zone II of L-Arg group
      was significantly higher than that in control group (<i>t</i>=9.428 and 
      3.054,<i>P</i><0.05 or <i>P</i><0.01). <b>Conclusion:</b> Exogenous L-Arg can
      increase the survival rate of extended dorsal perforator skin flap through
      promoting vascularization and dilatation of vessels in choke zone II in rats.

PMID- 29658671
TI  - [A case of insulinoma complicated with secondary adrenal insufficiency].
AB  - A middle-aged male patient with recurrent hypoglycemia was diagnosed as
      insulinoma according to the symptoms and the laboratory tests. Laboratory tests
      also showed low cortisol and adrenocortico-tropic hormone (ACTH) levels,
      therefore adrenal insufficiency was diagnosed and hydrocortisone was given. The
      hormone replacement therapy was terminated after surgery, and ACTH and cortisol
      levels returned to normal.

PMID- 29658672
TI  - [Present situation and prospect of enhanced recovery after surgery in pancreatic
      surgery].
AB  - Enhanced recovery after surgery is a multimodal perioperative strategy according
      to the evidence-based medicine and multidisciplinary collaboration, aiming to
      improve the restoration of functional capacity after surgery by reducing surgical
      stress, optimal control of pain, early oral diet and early mobilization. Compared
      with other sub-specialty in general surgery, pancreatic surgery is characterized
      by complex disease, highly difficult procedure and more postoperative
      complications. Accordingly, pancreatic surgery shares a slow development in
      enhanced recovery after surgery. In this review, the feasibility, safety,
      application progress, prospect and controversy of enhanced recovery after surgery
      in pancreatic surgery are discussed.

PMID- 29658673
TI  - [Application of rehabilitation medicine in enhanced recovery after surgery].
AB  - Enhanced recovery after surgery (ERAS) has been widely used in perioperative
      optimization. As an important component of ERAS, rehabilitation medicine mainly
      focuses on perioperative physical fitness management, respiratory training,
      exercise training to reduce the incidence of postoperative pulmonary infection,
      improve gastrointestinal and cardiopulmonary function. This paper explains
      rehabilitation medicine for respiratory, musculoskeletal, cardiovascular and
      digestive systems during the perioperative period.

PMID- 29658674
TI  - Resection of the caudate lobe for the treatment of hilar cholangiocarcinoma.
      Systematic review and meta-analysis.
AB  - INTRODUCTION: Whether the resection of the caudate lobe, in association with
      major hepatectomy, improves outcomes in hilar cholangiocarcinoma is
      controversial. EVIDENCE ACQUISITION: We performed a systematic literature review
      on all studies published from June 1979 to September 2016. Inclusion criteria for
      eligibility were the presence of parallel-groups of patients treated with major
      hepatectomy with either caudate lobe resection (CLR), or not (NCLR), in adult
      population, reporting data on overall survival (OS). We ran out a random-effect
      meta-analysis for survival data. EVIDENCE SYNTHESIS: Six retrospective studies
      with 969 patients (643 CLR and 326 NCLR) were included. The probability of death
      was significantly lower in CLR group than in NCLR group (HR 0.65; 95%CI 0.44
      0.97; p = 0.035). The median survival time was in favor of CLR (WMD 3.46; 95%CI
      1.02-5.90, p = 0.005]. Patients who underwent CLR were more likely to receive a
      R0 resection than those who did not (OR 8.26; 95% CI 2.45- 27.87; p = 0.001). No
      moderator effects were detected at meta-regression for operative time,
      postoperative complication rate and pathologic findings. CONCLUSIONS: Despite the
      paucity of data and the retrospective nature of the included studies, our results
      suggest that major hepatectomy plus caudate lobe resection may improve the
      likelihood of R0 resection and the overall survival in patients with hilar
      cholangiocarcinoma.

PMID- 29658676
TI  - A historical perspective on rectal cancer treatment: from the prehistoric era to
      the future.

PMID- 29658675
TI  - Local excision for rectal cancer: a minimally invasive option.
AB  - Transanal excision (TAE) with conventional retractors and transanal endoscopic
      microsurgery (TEM) are two well established minimally invasive surgical options
      for the treatment of selected rectal cancers. TEM is nowadays considered the
      standard of care for the transanal excision of rectal tumors, since it is
      associated with significantly better quality of excision and lower rates of
      recurrence than TAE. When compared with rectal resection and total mesorectal
      excision, TEM has lower postoperative morbidity and better functional outcomes,
      with similar long-term survival rates in selected early rectal cancers. More
      recently, transanal minimally invasive surgery (TAMIS) has been developed as an
      alternative to TEM. Possible benefits of TAMIS are under evaluation.

PMID- 29658677
TI  - Acute complications following endoscopic intragastric balloon insertion for
      treatment of morbid obesity in elderly patients. A single center experience.
AB  - BACKGROUND: Obesity is a serious disease, with an increasing incidence also among
      subjects over 60 years old; surgical management has proven to be the most
      effective in the production of significant and durable weight loss. Intragastric
      balloon (IGB) treatment, promotes a reduction of five to nine body mass index
      (BMI) units in 6 months with an impressive improvement of obesity-associated
      comorbidities. METHODS: Two hundred and twenty five patients, 106 men (47.1%) and
      119 women (52.9%), were evaluated at our institution to be submitted to a IGB
      positioning. Of these, 12 patients (8 women and 4 men) were more than 60 years
      old. For all patients BMI, co-morbidities, weight loss and complications were
      recorded. Chi-square test was used to evaluate differences in complications rate
      between elderly and other patients. RESULTS: For the 12 elderly patients, we
      recorded a mean excess weight loss rate (EWL%) of 31.4. About complications, we
      recorded 2 severe esophagitis requiring IGB removal and 1 late gastric
      perforation. A higher complications rate was found in elderly population and the
      comparison with other patients revealed a significant difference (p<0.001).
      CONCLUSIONS: Our results underline that IGB treatment in elderly patients is safe
      and effective in terms of weight loss and improvement in comorbidities. IGB can
      cause complications which, sometimes, can be severe such as esophageal damage and
      gastric perforation. For the management of complications, we highly recommend a
      close follow-up in all patients and a deepened instrumental study in every
      suspect case.

PMID- 29658678
TI  - Emergency surgery for bowel obstruction in extremely aged patients.
AB  - BACKGROUND: As a result of the increasing of life expectancy, the incidence of
      pathologies that can lead to operation for bowel obstruction is also increasing.
      Comorbidities and reduced physiological reserve can decrease elderly patients'
      ability to tolerate operations especially in an emergency context. We
      retrospectively evaluated the treatment and outcomes of a cohort of patients aged
      more than 85 years who underwent emergency surgery for intestinal occlusion.
      METHODS: 278 patients who were admitted to our Institution and operated for acute
      bowel obstruction have been included in our study. We divided the study
      population in 2 groups (group A: patients aged > 85 years old; group B patients
      aged <= 85 years). We evaluated the differences between the two groups in terms
      of intestinal occlusion aetiology, surgical procedures, morbidity and mortality
      rates. RESULTS: Group A consisted of 57 patients, group B of 221; elderly
      patients trend in ASA score classification was significantly towards high risk
      for elderly group; statistical analysis did not show differences in terms of
      bowel obstruction aetiology (except colon volvulus, more frequent in advanced
      age), type of procedure, duration of hospital stay, procedure - related
      complication rate. Perioperative mortality was significantly higher in elderly
      group, due to the mayor incidence of cardiovascular and respiratory fatal events
      directly related to pre - existing comorbidities. CONCLUSIONS: Despite the high
      surgical risk, early diagnosis and treatment of the obstructive disease can lead
      to achieve encouraging outcomes also in extremely advanced age; an aggressive
      evaluation of comorbidies and the cardio - respiratory risks reduction, when
      possible, could be useful in improve postoperative outcomes in terms of
      mortality.

PMID- 29658679
TI  - Iatrogenic spleen injury during minimally invasive left colonic flexure
      mobilization: the quest for evidence-based results.
AB  - INTRODUCTION: To assess the frequency, risk factors and outcomes of iatrogenic
      spleen injury during minimally invasive colo-rectal surgery with a particular
      focus on the routine splenic flexure mobilization tehcnique. EVIDENCE
      ACQUISITION: Exclusion criteria: 1) topic not pertinent to the main topic of the
      review; 2) all case reports, editorials, conference highlights were excluded.
      After a title and abstract first selection and a final full-text analysis has
      been performed. The results of the selected articles are presented. EVIDENCE
      SYNTHESIS: The iatrogenic splenic injury rate during colorectal surgery is 0.96%.
      The iatrogenic injuries cause around 20% of all splenectomy. Ligaments over
      traction is the most frequent mechanism of damage. The routine splenic flexure
      mobilization is a matter of scientific debate. Risk factors - open surgery, male
      sex, peripheral vascular disease, malignant neoplasia, diverticulitis, emergency
      surgery and teaching-hospital status. There is a risk difference according to the
      procedure: transverse colectomy has the highest risk, followed by left colectomy
      and total colectomy. CONCLUSIONS: The routine mobilization of the left colonic
      flexure is a debated topic. However, according to some authors (including our
      experience), this procedure is not a risk factor and it may be advantageous: 1)
      it does not excessively prolong the total operative time; 2) better surgical
      skills development; 3) the tension-related ischemia is avoided; 4) wider
      oncological dissection. Technical accuracy with cautious dissection/visualization
      can reduce the rate of iatrogenic splenic damage. Laparoscopy decreases the rate
      of splenic injury by almost 3.5 times. Robotic surgery may have the potential to
      further reduce this complication, but more data are needed on the topic.

PMID- 29658680
TI  - Rectal cancer and the pathologist.
AB  - Examination of the rectum by pathologists is instrumental in the management of
      patients affected by rectal carcinoma. That role includes evaluation of multiple
      gross and microscopic features that convey prognostic implications. The analysis
      is based on the authors' experience handling rectal specimens along with review
      of the pertinent literature in these areas: margins of excision, quality of the
      mesorectum, diligence and techniques to sample lymph nodes, tumor budding,
      grading of residual amount of carcinoma after preoperative therapy,
      vascular/perineural invasion, and staging the tumor. Pathologists must
      communicate the findings in a clear manner. Evaluation of margins and
      completeness of mesorectum are markers of the quality of surgical excision. The
      number of lymph nodes obtained and examined is dependent in great part on the
      diligence of the pathologist finding them in the mesenteric adipose tissue. There
      are grades for budding and response to prior chemoradiation therapy. The location
      of vascular invasion (extramural vs. intramural) may predict aggressive behavior.
      Pathologists proactively are to choose sections of tumor for molecular testing.
      Meticulous macro- and microscopic evaluation of specimens for rectal carcinoma by
      pathologist is needed to determine an accurate assessment of staging and other
      prognostic factors. The modern pathologists play a pivotal part in the care and
      management of patients suffering from rectal adenocarcinoma. That role goes from
      the initial histological diagnosis to the gross and microscopic examination of
      the excised specimens. Based on that examination pathologists issue statements
      that not only evaluate the quality of the surgical procedure, but also through
      the application of molecular tests they give light on prognostic factors and
      information for therapeutic purposes.

PMID- 29658681
TI  - Laparoscopic radical prostatectomy in 2018: 20 years of worldwide experiences,
      experimentations, researches and refinements.
AB  - INTRODUCTION: After the first feasibility report in 1997, a growing interest has
      risen in the urologic community for laparoscopic radical prostatectomy (LRP) and
      several authors have contributed to the evolution of the technique. We attempt a
      review of the available evidences and provide a broad framework of different
      technical refinements considering their impact on pentafecta. EVIDENCE
      ACQUISITION: The PubMed/Medline database was searched. Duplicates and "Expert
      opinion" papers were removed. Studies were included according to the aim of the
      present paper to present a selected review on LRP and report our personal
      experience. EVIDENCE SYNTHESIS: In 1999 Guillonneau et al codified their
      transperitoneal-posterior-antegrade technique for LRP. Since then, several
      modifications of the transperitoneal approach were published and the
      extraperitoneal route was also proposed. Sparing the bladder neck and
      reconstructing the posterior muscolofascial plate were proven to improve
      continence rate. Nerve- sparing LRP were performed in order to maximize post
      operative recovery of the sexual function. Novel techniques to ligate the
      Santorini plexus and sew the urethrovesical anastomosis provided improvement in
      operative time, intraoperative blood loss and reduced the incidence of
      postoperative urinary-leakages. In the recent years, the single-site approach as
      pushed the limits of LRP and three-dimensional (3D) systems for endoscopic
      surgery were developed. CONCLUSIONS: Thanks to several technical improvements,
      LRP provides brilliant oncologic and functional outcomes and it is now considered
      the treatment of choice in many institutions worldwide. Although it is a
      technically demanding procedure, the recent introduction of 3D systems will
      reduce the steepness of its learning curve.

PMID- 29658683
TI  - Extrafascial robot-assisted laparoscopic radical prostatectomy (EF-RALP) in
      locally advanced prostate cancer.
AB  - INTRODUCTION: Up to 26.5% of new dewly diagnosed prostate cancers (PCa) are
      locally advanced (LA). Although traditionally discouraged in this setting,
      radical prostatectomy (RP) lowers the risk of metastatic progression and cancer
      specific death. We report a review of the available evidences and describe our
      surgical technique of Extrafascial robot-assisted RP. EVIDENCE ACQUISITION: The
      PubMed/Medline database was searched for "prostate cancer", "high-risk", "locally
      advanced", "prostatectomy". Duplicates and expert opinion papers were removed.
      EVIDENCE SYNTHESIS: RP is an option in selected patients with LA-PCa and >10
      years life expectancy. Five, 10 and 15 years after open RP, disease free survival
      rates were 85%, 73% and 67%. At the same time-points, cancer specific survival
      and overall survival were 95%, 90%, 79% and 90%, 76%, 53%, respectively. Post
      operative potency was achieved by 25% of the patients while 79% were continent.
      Robotic prostatectomy provides comparable cancer control outcomes, but it is
      associated with a lower transfusion rate and a shorter hospitalization time. The
      concept of "extrafascial prostatectomy" was introduced in 2000 by Villers: this
      surgical approach reduces the incidence of mid- and postero-lateral positive
      margins (28% vs 51%, when compared to intrafascial; p = 0.08), expecially in pT3
      cancers, but markedly affects potency. CONCLUSIONS: Robot-assisted RP is an
      option in patients with LA-PCa. Removing the prostate gland and the seminal
      vesicles still contained inside their aponeurotic covering, minimize the risk of
      positive surgical margins and clinical recurrence.

PMID- 29658682
TI  - Sphincter-saving proctectomy for rectal cancer with transanal tube NO COIL and
      without ostoma: clinical outcomes, cost effectiveness and quality of life in
      elderly.
AB  - BACKGROUND: Colorectal cancer is one of the most common invasive cancers, and it
      is responsible for considerable physical and psychosocial morbidity specially in
      older patients. However, only few reports focused on quality of life, cost
      effectiveness and clinical outcomes of rectal cancer patients undergone to
      surgery. This retrospective study compares short-term and long- term outcomes in
      rectal cancer patients with more and less 75 years of age. METHODS: Four hundred
      consecutive patients underwent to radical surgery for rectal adenocarcinoma and
      they were collected in a prospective institutional database and divided into two
      groups: group 1 (>= 75 years, n =98); group 2 (<75 years, n=302). Rectal anterior
      resection (RAR) with sphincter-saving restorative proctectomy and with
      application of silicone transanal tube NO COIL (r) 60-80 mm long, was the only
      procedure considered. Main clinical and pathological data were assessed and
      compared. RESULTS: Statistically significant differences between the two groups
      were detected regard to comorbidities and the emergency presentation. Overall
      survival is lower in patients over 75 age, but cancer-related survival is not
      different between the two groups. CONCLUSIONS: Although advanced age is
      associated with higher morbidity and mortality, in our experience, itself is not
      a contraindication for surgical sphincter-saving proctetomy in rectal cancer
      patients. The absence of a stoma improve also, in both groups, the cost
      effectiveness and the patients quality of life: psychological morbidity,
      sexuality, levels of anxiety and depression, body image.

PMID- 29658684
TI  - Role of adjuvant chemoradiotherapy after endoscopic treatment of early-stage
      esophageal cancer: a systematic review.
AB  - INTRODUCTION: Esophagectomy combined with lymphadenectomy is currently
      recommended for patients with high-risk early-stage esophageal cancer after
      endoscopic treatment (i.e. submucosal tumor invasion [sm2-3], presence of
      lymphovascular invasion and/or poor tumor differentiation) given the high risk of
      lymph node metastases. Unfortunately, some patients do not have the physiologic
      capability to endure surgery. For these patients chemoradiotherapy (CRT)
      following endoscopic treatment could be an alternative. The aim of this
      systematic review was to evaluate the evidence on the safety and efficacy of
      endoscopic treatment combined with CRT in patients with high-risk early-stage
      esophageal cancer. EVIDENCE ACQUISITION: A systematic literature search was
      performed to identify studies reporting on the safety and efficacy of CRT
      following endoscopic mucosal resection (EMR) or endoscopic submucosal dissection
      (ESD) in patients with esophageal cancer invading the muscularis mucosae or
      submucosa. Primary outcomes were locoregional recurrence (LRR), disease-free
      survival (DFS) and overall survival (OS). The secondary outcome was the
      occurrence of treatment-related adverse events. EVIDENCE SYNTHESIS: Six studies
      were included, comprising a total of 168 patients with early-stage esophageal
      cancer that underwent endoscopic treatment followed by CRT. Most studies were
      retrospective case series and included small numbers of patients (11 to 66). All
      patients had T1a(m3) or T1b(sm1-3) esophageal squamous cell carcinoma. Adjuvant
      treatment consisted of cisplatin and 5-fluorouracil with concurrent radiotherapy;
      doses ranging from 40 to 60 Gy. The overall LRR rate ranged between 0-9%.
      Reported 3-year DFS and OS rates ranged between 69-100% and 87-100%,
      respectively. In all studies ESD and/or EMR was safely performed without serious
      complications. The observed CRT treatment-related toxicity (grade >=3) ranged
      between 0% and 32%. CONCLUSIONS: This review demonstrates that the current
      available literature lacks large prospective adequately powered studies and does
      not allow any firm conclusion regarding the role of endoscopic treatment combined
      with adjuvant CRT for patients with high-risk early-stage esophageal cancer.

PMID- 29658685
TI  - Minimally invasive posterior extraforaminal approach for presacral schwannoma of
      L5: a technical note.

PMID- 29658686
TI  - Management decisions in treating large vestibular schwannoma: a staged technique.

PMID- 29658687
TI  - Influence of Growth Temperature on the Characteristics of Single-Junction p-i-n
      InGaP Solar Cells.
AB  - Single-junction p-i-n InGaP solar cells are grown at various temperatures from
      620 to 700  degrees C by low pressure metalorganic chemical vapor deposition on
      GaAs (001) substrates. The short circuit current density of the p-i-n InGaP solar
      cells increases by up to 38.8% when the growth temperature is reduced from 700 to
      620  degrees C, while the open circuit voltage and fill factor show relatively
      small changes. The external quantum efficiency, especially, in the wavelength
      regime below 500 nm, is improved for the p-i-n InGaP solar cells grown at lower
      temperatures. The improvement might be attributed to the reduced absorption loss
      of the photons in the n-InGaP emitter region. The highest conversion efficiency
      of 11.01% is attributed from the p-i-n InGaP solar cell grown at 640  degrees C.
      Electron mobility and concentration of undoped InGaP layers are investigated as a
      function of the growth temperature and correlated with the p-i-n InGaP solar cell
      performance.

PMID- 29658688
TI  - Low Permeable Hydrocarbon Polymer Electrolyte Membrane for Vanadium Redox Flow
      Battery.
AB  - Polymer electrolyte membrane (PEM) confirms the life span of vanadium redox flow
      battery (VRFB). Products from Dupont, Nafion membrane, is mainly used for PEM in
      VRFB. However, permeation of vanadium ion occurs because of Nafion's high
      permeability. Therefore, the efficiency of VRFB decreases and the prices becomes
      higher, which hinders VRFB's commercialization. In order to solve this problem,
      poly(phenylene oxide) (PPO) is sulfonated for the preparation of low-priced
      hydrocarbon polymer electrolyte membrane. sPPO membrane is characterized by
      fundamental properties and VRFB cell test.

PMID- 29658689
TI  - Direct Conversion of Methane Over Oxide-Type Catalysts Supported on Mesoporous
      Silica Under Electric Discharge.
AB  - Direct conversion of methane over oxide-type catalysts supported on mesoporous
      material under the dielectric barrier discharge plasma was investigated in the
      present study. The oxide catalysts (MgO and NiO) supported on SBA-15 was prepared
      by a hydrothermal and wet-impregnation method. The low-angle XRD patterns and TEM
      indicate that the ordered mesoporous structure was well maintained during the
      catalyst preparation and reaction processes. We also conducted direct conversion
      of methane using the catalysts under the plasma. As a result, the specific
      surface area of bare SBA-15 was much higher than that of the NiO/SBA-15, followed
      by MgO/SBA-15. Overall, the CH4 conversion increased with increasing the specific
      surface area. And C2 selectivity decreased with increasing the specific surface
      area.

PMID- 29658690
TI  - Tin Oxide/Carbon Nanocomposites as the Electrode Material for Supercapacitors
      Using a Liquid Phase Plasma Method.
AB  - Tin oxide/carbon nanocomposite (TOCNC) was synthesized using a liquid phase
      plasma method, to be used as the electrode of supercapacitor. Spherical tin oxide
      amorphous nanoparticles with the size of 5 nm were dispersed uniformly on
      activated carbon powder (ACP) surface. The quantity of tin oxide nanoparticle
      precipitate increased with increasing LPP duration and the specific capacitance
      of TOCNC increased with increasing LPP duration. The TOCNC prepared through the
      LPP process showed smaller resistances and larger initial resistance slopes than
      bare ACP and this effect was intensified by increasing the LPP process duration.

PMID- 29658691
TI  - Design and Fabrication of Implantable Neural Probes with Monolithically
      Integrated Light-Emitting Diodes for Optogenetic Applications.
AB  - We report an implantable neural probe with monolithically integrated light
      emitting diodes (LEDs) and recording site for optogenetic applications. The
      device were designed and fabricated with 2-inch gallium nitride on silicon
      epitaxial wafer. The neural probe consisted of three MULEDs (a mesa size of 310 *
      41 mm2) and four electrical recording sites, which had a total length of 6.72 mm
      (PCB bonding region + implanting region). The designed implantable neural probe
      was successfully processed by the conventional LED fabrication and Si
      microfabrcation. These methods can offer relatively rapid and easy fabrication.
      For fabricated MULEDs, the optical and electrical properties were measured and
      characterized. At 1 mA, the emission wavelength was around 460 nm and it was
      slightly blue-shifted with the increase of injection current. Also, the optical
      power density was about 1 mW/mm2 at an electrical input power of 3.5 mW, and it
      was increased to 6.3 mW/mm2 at 24 mW.

PMID- 29658692
TI  - Efficient Transport Networks in a Dual Electron/Lithium-Conducting Polymeric
      Composite for Electrochemical Applications.
AB  - In this work, an all-functional polymer material composed of the electrically
      conductive poly(3,4-ethylenedioxythiophene):poly(4-styrenesulfonic acid)
      (PEDOT:PSS) and lithium-conducting poly(ethylene oxide) (PEO) was developed to
      form a dual conductor for three-dimensional electrodes in electrochemical
      applications. The composite exhibits enhanced ionic conductivity (~10-4 S cm-1)
      and, counterintuitively, electronic conductivity (~45 S cm-1) with increasing PEO
      proportion, optimal at a monomer ratio of 20:1 PEO:PEDOT. Microscopy reveals a
      unique morphology, where PSS interacts favorably with PEO, destabilizing PEDOT to
      associate into highly branched, interconnected networks that allow for more
      efficient electronic transport despite relatively low concentrations. Thermal and
      X-ray techniques affirm that the PSS-PEO domain suppresses crystallinity,
      explaining the high ionic conductivity. Electrochemical experiments in lithium
      cell environments indicate stability as a function of cycling and improved
      overpotential due to dual transport characteristics despite known issues with
      both individual components.

PMID- 29658693
TI  - Polyacrylamide Gel-Contained Zinc Finger Peptide as the "Lock" and Zinc Ions as
      the "Key" for Construction of Ultrasensitive Prostate-Specific Antigen SERS
      Immunosensor.
AB  - In this work, we adopted polyacrylamide gel-contained zinc finger peptide (PZF)
      as a "lock" of Raman signal and zinc ions (Zn2+) as a sensitive "key", which was
      converted from target-captured ZnO NPs, to achieve the measurement of prostate
      specific antigen (PSA). Owing to the lock effect from PZF, the surface-enhanced
      Raman scattering (SERS) tag toluidine blue (TB) connected on Ag NP-coating silica
      wafer was sheltered leading to low Raman response. Meanwhile, target PSA can
      specifically connect with antibody 2-coupled ZnO nanocomplexes (ZnO@Au@Ab2) and
      antibody 1-coupled magnetic (CoFe2O4@Au@Ab1) nanocomposite through sandwich
      immunoassay. In the presence of HCl, the ZnO NPs would convert into Zn2+ to open
      the PZF because Zn2+ can specifically react with zinc finger peptide to destroy
      the PZF structure forming abundant pores. In this way, Zn2+ could act as the key
      of Raman signal to open the PZF structure obtaining a strong Raman signal of TB.
      The proposed SERS sensor can have a quantitative detection of PSA within the
      range of 1 pg mL-1 to 10 ng mL-1 with a detection limit of 0.65 pg mL-1. The
      interaction between zinc finger peptide and Zn2+ was firstly applied in SERS
      sensor for the sensitive detection of PSA. These results demonstrated that the
      new designed SERS biosensor could be a promising tool in biomarker diagnosis.

PMID- 29658694
TI  - Giant Negative Piezoresistive Effect in Diamond-like Carbon and Diamond-like
      Carbon-Based Nickel Nanocomposite Films Deposited by Reactive Magnetron
      Sputtering of Ni Target.
AB  - Piezoresistive properties of hydrogenated diamond-like carbon (DLC) and DLC-based
      nickel nanocomposite (DLC:Ni) films were studied in the range of low
      concentration of nickel nanoparticles. The films were deposited by reactive high
      power pulsed magnetron sputtering (HIPIMS) of Ni target, and some samples were
      deposited by direct current (dc) reactive magnetron sputtering for comparison
      purposes. Raman scattering spectroscopy, energy-dispersive X-ray spectrometry
      (EDS), and X-ray photoelectron spectroscopy (XPS) were used to study the
      structure and chemical composition of the films. A four-point bending test was
      applied to study piezoresistive properties of the films. For some samples
      containing less than 4 at. % Ni and for the samples containing no Ni (as defined
      by both EDS and XPS), a giant negative piezoresistive effect was observed. The
      giant negative piezoresistive effect in DLC films deposited by either reactive
      HIPIMS or dc magnetron sputtering of Ni target was explained by possible
      clustering of the sp2-bonded carbon and/or formation of areas with the decreased
      hydrogen content. It was suggested that the tensile stress-induced rearrangements
      of these conglomerations have resulted in the increased conductivity paths.

PMID- 29658695
TI  - PdAg Bimetallic Nanoalloy-Decorated Graphene: A Nanohybrid with Unprecedented
      Electrocatalytic, Catalytic, and Sensing Activities.
AB  - Recent reports about the promising and tunable electrocatalytic activity and
      stability of nanoalloys have stimulated an intense research activity toward the
      design and synthesis of homogeneously alloyed novel bimetallic
      nanoelectrocatalysts. We herein present a simple one-pot facile wet-chemical
      approach for the deposition of high-quality bimetallic palladium-silver (PdAg)
      homogeneous nanoalloy crystals on reduced graphene (Gr) oxide sheets.
      Morphological, structural, and chemical characterizations of the so-crafted
      nanohybrids establish a homogeneous distribution of 1:1 PdAg nanoalloy crystals
      supported over reduced graphene oxide (PdAg-Gr). The PdAg-Gr nanohybrids exhibit
      outstanding electrocatalytic, catalytic, and electroanalytical performances. The
      PdAg-Gr samples were found to exhibit exceptional durability when subjected to
      repeated potential cycles or long-term electrolysis. In the CVs recorded for fuel
      cell reactions, viz. methanol oxidation reaction and oxygen reduction reaction,
      and for detoxification of environmental pollutants, viz. electroreduction of
      methyl iodide and chloroacetonitrile over PdAg-Gr with potential sweep rate of 25
      mVs-1, the peak potentials were observed to be just -0.221, -0.297, (vs Ag/AgCl,
      3 M KCl) -1.508, and -1.189 V (vs Fc+/Fc), respectively. The potential of PdAg-Gr
      nanohybrid for simultaneous and sensitive electrochemical sensing and estimation
      of hydroxybenzene isomers with very low detection limits (0.05 MUM for
      hydroquinone, 0.06 MUM for catechol, 6.7 nM for 4-aminophenol, and 13.7 nM for 2
      aminophenol) is demonstrated. Additionally, PdAg-Gr was observed to offer
      excellent solution-phase catalytic performance in bringing about the reduction of
      notorious environmental pollutant 4-nitrophenol to pharmaceutically important 4
      aminophenol with an apparent rate constant ( kapp) of 3.106 * 10-2 s-1 and a
      normalized rate constant ( knor) of 6.21 * 102 s-1 g-1. The presented synthetic
      scheme besides being high yielding, low cost, and easy to carry out results in
      the production of PdAg-Gr nanohybrids with stability and activity significantly
      better than most of the nanomaterials purposefully designed and testified so far
      by various groups.

PMID- 29658697
TI  - Enhanced Impact Resistance of Three-Dimensional-Printed Parts with Structured
      Filaments.
AB  - Net-shape manufacture of customizable objects through three-dimensional (3D)
      printing offers tremendous promise for personalization to improve the fit,
      performance, and comfort associated with devices and tools used in our daily
      lives. However, the application of 3D printing in structural objects has been
      limited by their poor mechanical performance that manifests from the layer-by
      layer process by which the part is produced. Here, this interfacial weakness is
      overcome using a structured, core-shell polymer filament where a polycarbonate
      (PC) core solidifies quickly to define the shape, whereas an olefin ionomer shell
      contains functionality (crystallinity and ionic) that strengthen the interface
      between the printed layers. This structured filament leads to improved
      dimensional accuracy and impact resistance in comparison to the individual
      components. The impact resistance from structured filaments containing 45 vol %
      shell can exceed 800 J/m. The origins of this improved impact resistance are
      probed using X-ray microcomputed tomography. Energy is dissipated by delamination
      of the shell from PC near the crack tip, whereas PC remains intact to provide
      stability to the part after impact. This structured filament provides tremendous
      improvements in the critical properties for manufacture and represents a major
      leap forward in the impact properties obtainable for 3D-printed parts.

PMID- 29658696
TI  - Improved Method for the Incorporation of Heme Cofactors into Recombinant Proteins
      Using Escherichia coli Nissle 1917.
AB  - Recombinant production of heme proteins in Escherichia coli is often limited by
      the availability of heme in the host. Therefore, several methods, including the
      reconstitution of heme proteins after production but prior to purification or the
      HPEX system, conferring the ability to take up external heme have been developed
      and used in the past. Here we describe the use of the apathogenic E. coli strain
      Nissle 1917 (EcN) as a suitable host for the recombinant production of heme
      proteins. EcN has an advantage over commonly used lab strains in that it is able
      to take up heme from the environment through the heme receptor ChuA. Expression
      of several heme proteins from different prokaryotic sources led to high yield and
      quantitative incorporation of the cofactor when heme was supplied in the growth
      medium. Comparative UV-vis and resonance Raman measurements revealed that the
      method employed has significant influence on heme coordination with the EcN
      system representing the most native situation. Therefore, the use of EcN as a
      host for recombinant heme protein production represents an inexpensive and
      straightforward method to facilitate further investigations of structure and
      function.

PMID- 29658698
TI  - Hydrophobic Antifouling Electrospun Mats from Zwitterionic Amphiphilic
      Copolymers.
AB  - A porous material that is both hydrophobic and fouling-resistant is needed in
      many applications, such as water purification by membrane distillation. In this
      work, we take a novel approach to fabricating such membranes. Using the
      zwitterionic amphiphilic copolymer poly(trifluoroethyl methacrylate- random
      sulfobetaine methacrylate), we electrospin nonwoven, porous membranes that
      combine high hydrophobicity with resistance to protein adsorption. By changing
      the electrospinning parameters and the solution composition, membranes can be
      prepared with a wide range of fiber morphologies including beaded, bead-free,
      wrinkly, and ribbonlike fibers, with diameters ranging between ~150 nm and 1.5
      MUm. The addition of LiCl to the spinning solution not only helps control the
      fiber morphology but also increases the segregation of zwitterionic groups on the
      membrane surface. The resultant electrospun membranes are highly porous and very
      hydrophobic, yet resist the adsorption of proteins and retain a high contact
      angle (~140 degrees ) even after exposure to a protein solution. This makes these
      materials promising candidates for the membrane distillation of contaminated
      wastewater streams and as self-cleaning materials.

PMID- 29658699
TI  - Facile Synthesis of a Pentiptycene-Based Highly Microporous Organic Polymer for
      Gas Storage and Water Treatment.
AB  - Rigid H-shaped pentiptycene units, with an intrinsic hierarchical structure, were
      employed to fabricate a highly microporous organic polymer sorbent via Friedel
      Crafts reaction/polymerization. The obtained microporous polymer exhibits good
      thermal stability, a high Brunauer-Emmett-Teller surface area of 1604 m2 g-1,
      outstanding CO2, H2, and CH4 storage capacities, as well as good adsorption
      selectivities for the separation of CO2/N2 and CO2/CH4 gas pairs. The CO2 uptake
      values reached as high as 5.00 mmol g-1 (1.0 bar and 273 K), which, along with
      high adsorption selectivity values (e.g., 47.1 for CO2/N2), make the pentiptycene
      based microporous organic polymer (PMOP) a promising sorbent material for carbon
      capture from flue gas and natural gas purification. Moreover, the PMOP material
      displayed superior absorption capacities for organic solvents and dyes. For
      example, the maximum adsorption capacities for methylene blue and Congo red were
      394 and 932 mg g-1, respectively, promoting the potential of the PMOP as an
      excellent sorbent for environmental remediation and water treatment.

PMID- 29658700
TI  - 3D-Printed Graphene/Polylactic Acid Electrodes Promise High Sensitivity in
      Electroanalysis.
AB  - Additive manufacturing provides a unique tool for prototyping structures toward
      electrochemical sensing, due to its ability to produce highly versatile, tailored
      shaped devices in a low-cost and fast way with minimized waste. Here we present
      3D-printed graphene electrodes for electrochemical sensing. Ring- and disc-shaped
      electrodes were 3D-printed with a Fused Deposition Modeling printer and
      characterized using cyclic voltammetry and scanning electron microscopy.
      Different redox probes K3Fe(CN)6:K4Fe(CN)6, FeCl3, ascorbic acid, Ru(NH3)6Cl3,
      and ferrocene monocarboxylic acid) were used to assess the electrochemical
      performance of these devices. Finally, the electrochemical detection of picric
      acid and ascorbic acid was carried out as proof-of-concept analytes for sensing
      applications. Such customizable platforms represent promising alternatives to
      conventional electrodes for a wide range of sensing applications.

PMID- 29658701
TI  - Functional Annotation of LigU as a 1,3-Allylic Isomerase during the Degradation
      of Lignin in the Protocatechuate 4,5-Cleavage Pathway from the Soil Bacterium
      Sphingobium sp. SYK-6.
AB  - Sphingobium sp. SYK-6 is a Gram-negative soil bacterium that contributes to the
      degradation of lignin. Lignin provides structural support and protection to
      plants as a complex aromatic heteropolymer. The lignin degradation pathway of
      guaiacyl moieties leads to the intermediate, protocatechuate (PCA), which is
      further degraded via the 4,5-cleavage pathway in which PCA is ultimately
      metabolized to pyruvate and oxaloacetate. In this pathway, LigI has been shown to
      catalyze the hydrolysis of 2-pyrone-4,6-dicarboxylate to (4 E)-oxalomesaconate
      (OMA). Here we have demonstrated, using 1H and 13C nuclear magnetic resonance
      spectroscopy, that LigU catalyzes the isomerization of the double bond between C4
      and C5 in (4 E)-OMA to (3 Z)-2-keto-4-carboxy-3-hexenedioate (KCH), where the
      double bond has migrated to be between C3 and C4 via a 1,3-allylic isomerization.
      LigU is most closely related in amino acid sequence to methylaconitate isomerase
      (PrpF) from Shewanella oneidensis and methylitaconate-Delta-isomerase (Mii) from
      Eubacterium barkeri. The kinetic constants for the isomerization of OMA to KCH by
      LigU at pH 8.0 were determined to be 1300 +/- 120 s-1 and (7.7 +/- 1.5) * 106 M-1
      s-1 for kcat and kcat/ Km, respectively. We have also shown that the product of
      the LigU-catalyzed reaction is the preferred substrate for the LigJ hydratase. In
      this reaction, LigJ catalyzes the hydration of KCH to 4-carboxy-4-hydroxy-2
      oxoadipate.

PMID- 29658702
TI  - Inhibition and Regulation of the Ergothioneine Biosynthetic Methyltransferase
      EgtD.
AB  - Ergothioneine is an emerging factor in cellular redox homeostasis in bacteria,
      fungi, plants, and animals. Reports that ergothioneine biosynthesis may be
      important for the pathogenicity of bacteria and fungi raise the question as to
      how this pathway is regulated and whether the corresponding enzymes may be
      therapeutic targets. The first step in ergothioneine biosynthesis is catalyzed by
      the methyltransferase EgtD that converts histidine into N-alpha
      trimethylhistidine. This report examines the kinetic, thermodynamic and
      structural basis for substrate, product, and inhibitor binding by EgtD from
      Mycobacterium smegmatis. This study reveals an unprecedented substrate binding
      mechanism and a fine-tuned affinity landscape as determinants for product
      specificity and product inhibition. Both properties are evolved features that
      optimize the function of EgtD in the context of cellular ergothioneine
      production. On the basis of these findings, we developed a series of simple
      histidine derivatives that inhibit methyltransferase activity at low micromolar
      concentrations. Crystal structures of inhibited complexes validate this structure
      and mechanism-based design strategy.

PMID- 29658703
TI  - Robust and Conductive Red MoSe2 for Stable and Fast Lithium Storage.
AB  - Two-dimensional (2D) layered transition-metal dichalcogenides (LTMDs) display
      various crystal phases with distinct symmetries, structures, and physical
      properties. Exploring and designing different structural phases in two dimensions
      could provide an avenue for switching material properties, aiming at practical
      applications for potential fields. Here we demonstrate a conceptually designed
      approach to narrow the band gap of MoSe2 and obtain a conductive red MoSe2
      nanosheet. By introducing the high valence state of Mo species and constructing
      the Mo-O bonding on the surface of the MoSe2 nanosheets, the electronic
      properties can be modified and the conductivity is accordingly improved, an
      effect that significantly improves their lithium storage capacity and high-rate
      capability. We anticipate that the exploration of the conductive red MoSe2 with
      tunable band gap could help us unlock more potential crystal structures of LTMD
      based and even other 2D materials for further applications.

PMID- 29658704
TI  - Identification of Noncatalytic Lysine Residues from Allosteric Circuits via
      Covalent Probes.
AB  - Covalent modifications of nonactive site lysine residues by small molecule probes
      has recently evolved into an important strategy for interrogating biological
      systems. Here, we report the discovery of a class of bioreactive compounds that
      covalently modify lysine residues in DegS, the rate limiting protease of the
      essential bacterial outer membrane stress response pathway. These modifications
      lead to an allosteric activation and allow the identification of novel residues
      involved in the allosteric activation circuit. These findings were validated by
      structural analyses via X-ray crystallography and cell-based reporter systems. We
      anticipate that our findings are not only relevant for a deeper understanding of
      the structural basis of allosteric activation in DegS and other HtrA serine
      proteases but also pinpoint an alternative use of covalent small molecules for
      probing essential biochemical mechanisms.

PMID- 29658705
TI  - Tungsten Hydride Phosphorus- and Arsenic-Bearing Molecules with Double and Triple
      W-P and W-As Bonds.
AB  - Laser ablation of tungsten metal provides W atoms which react with phosphine and
      arsine during condensation in excess argon and neon, leading to major new
      infrared (IR) absorptions. Annealing, UV irradiation, and deuterium substitution
      experiments coupled with electronic structure calculations at the density
      functional theory level led to the assignment of the observed IR absorptions to
      the E=WH3 and HE?WH2 molecules for E = P and As. The potential energy surfaces
      for hydrogen transfer from PH3 to the W were calculated at the coupled-cluster
      CCSD(T)/complete basis set level. Additional weak bands in the phosphide and
      arsenide W-H stretching region are assigned to the molecules with loss of H from
      W, E=WH2. The electronic structure calculations show that the E=WH3 molecules
      have a W-E triple bond, the HE?WH2 molecules have a W-E double bond, and the H2E
      WH molecules have a W-E single bond. The formation of multiple E-W bonds leads to
      increasing stability for the isomers.

PMID- 29658706
TI  - Differences in the Triacylglycerol and Fatty Acid Compositions of Human Colostrum
      and Mature Milk.
AB  - Human colostrum is important for immune system development and plays a protective
      role for infants. However, the comprehensive exploration of lipids, which account
      for 3-5% of milk, and their biological functions in human colostrum was limited.
      In present study, the triacylglycerol (TAG) and fatty acid (FA) compositions of
      human colostrum and mature milk were analyzed and compared. Variations were
      observed in both the TAG and FA compositions. The concentrations of
      18:1/18:1/16:0 TAG, high-molecular-weight and unsaturated TAGs were significantly
      higher in colostrum, whereas mature milk contained more low/medium-molecular
      weight TAGs and medium-chain FAs. Furthermore, there were also specific TAGs in
      both colostrum and mature milk. Our data highlighted targets for further
      investigation to elucidate the biological function of lipids in colostrum milk.
      In addition, the comprehensive analysis of TAGs in Chinese colostrum might help
      in designing infant formula for Chinese babies, especially the preterm ones.

PMID- 29658708
TI  - Halogen Photoelimination from SbV Dihalide Corroles.
AB  - Main-group p-block metals are ideally suited for mediating two-electron reactions
      because they cycle between M n and M n+2 redox states, as the one-electron state
      is thermodynamically unstable. Here, we report the synthesis and structure of an
      SbIII corrole and its SbVX2 (X = Cl, Br) congeners. SbIII sits above the corrole
      ring, whereas SbV resides in the corrole centroid. Electrochemistry suggests
      interconversion between the SbIII and SbVX2 species. TD-DFT calculations indicate
      a HOMO -> LUMO+2 parentage for excited states in the Soret spectral region that
      have significant antibonding character with respect to the Sb-X fragment. The
      photochemistry of 2 and 3 in THF is consistent with the computational results, as
      steady-state photolysis at wavelengths coincident with the Soret absorption of
      SbVX2 corrole lead to its clean conversion to the SbIII corrole. This ability to
      photoactivate the Sb-X bond reflects the proclivity of the pnictogens to rely on
      the PnIII/V couple to drive the two-electron photochemistry of M-X bond
      activation, an essential transformation needed to develop HX-splitting cycles.

PMID- 29658709
TI  - Transformation of Polycyclic Aromatic Hydrocarbons and Formation of
      Environmentally Persistent Free Radicals on Modified Montmorillonite: The Role of
      Surface Metal Ions and Polycyclic Aromatic Hydrocarbon Molecular Properties.
AB  - This paper presents the transformation of PAHs (phenanthrene, anthracene,
      benzo[a]anthracene, pyrene, and benzo[a]pyrene) on montmorillonite clays that are
      modified by transition-metal ions [Fe(III), Cu(II), Ni(II), Co(II), or Zn(II)] at
      room temperature (~23  degrees C). The decay of these PAHs follows first-order
      kinetics, and the dependence of the observed rate constants ( kobs, day-1) on the
      presence of metal ions follows the order Fe(III) > Cu(II) > Ni(II) > Co(II) >
      Zn(II). The values of kobs show reasonable linear relationships with the
      oxidation potentials of the PAHs and the redox potentials of the metal ions.
      Notably, transformation of these PAHs results in the formation of environmentally
      persistent free radicals (EPFRs), which are of major concern due to their adverse
      effects on human health. The potential energy surface (PES) calculations using
      density functional theory were performed to understand the trends in kobs and the
      plausible mechanisms for radical formation from the PAHs on modified clays. The
      yields and stability of these EPFRs from anthracene and benzo[a]pyrene on clay
      surfaces varies with both the parent PAH and the metal ion. The results
      demonstrated the potential role of metals in the formation and fate of PAH
      induced EPFR at co-contaminated sites.

PMID- 29658710
TI  - [Ag2M(Te2O5)2]SO4 (M = CeIV or ThIV): A New Purely Inorganic d/f-Heterometallic
      Cationic Material.
AB  - Two new isotypic d/f-heterometallic purely inorganic cationic materials,
      [Ag2M(Te2O5)2]SO4 (M = CeIV or ThIV), were synthesized using the metal oxides
      (MO2 and TeO2), silver nitrate, and sulfuric acid under mild hydrothermal
      conditions. The prepared materials were characterized via single-crystal X-ray
      diffraction, which revealed that the materials possess a 3D framework of corner
      sharing Te2O52- units. The tellurite framework creates four unique pores, three
      of which are occupied by the MIV and AgI metal centers. The tellurite network,
      metal coordination, and total charge yield a cationic framework, which is charge
      balanced by electrostatically bound sulfate anions residing in the largest of the
      four framework pores. These materials also possess AgI in a ligand-imposed linear
      geometry.

PMID- 29658711
TI  - Oxidative Radical Intermolecular Trifluoromethylthioarylation of Styrenes by
      Arenediazonium Salts and Copper(I) Trifluoromethylthiolate.
AB  - An efficient oxidative radical intermolecular trifluoromethylthioarylation of
      styrenes with arenediazonium salts and copper(I) trifluoromethylthiolate under
      mild conditions is described for the first time. The reactions provide good
      yields of the corresponding trifluoromethylthioarylation products with broad
      substrate scope and excellent functional group compatibility.

PMID- 29658712
TI  - Sharp Transition from Nonmetallic Au246 to Metallic Au279 with Nascent Surface
      Plasmon Resonance.
AB  - The optical properties of metal nanoparticles have attracted wide interest.
      Recent progress in controlling nanoparticles with atomic precision (often called
      nanoclusters) provide new opportunities for investigating many fundamental
      questions, such as the transition from excitonic to plasmonic state, which is a
      central question in metal nanoparticle research because it provides insights into
      the origin of surface plasmon resonance (SPR) as well as the formation of
      metallic bond. However, this question still remains elusive because of the
      extreme difficulty in preparing atomically precise nanoparticles larger than 2
      nm. Here we report the synthesis and optical properties of an atomically precise
      Au279(SR)84 nanocluster. Femtosecond transient absorption spectroscopic analysis
      reveals that the Au279 nanocluster shows a laser power dependence in its excited
      state lifetime, indicating metallic state of the particle, in contrast with the
      nonmetallic electronic structure of the Au246(SR)80 nanocluster. Steady-state
      absorption spectra reveal that the nascent plasmon band of Au279 at 506 nm shows
      no peak shift even down to 60 K, consistent with plasmon behavior. The sharp
      transition from nonmetallic Au246 to metallic Au279 is surprising and will
      stimulate future theoretical work on the transition and many other relevant
      issues.

PMID- 29658713
TI  - Stabilization Mechanism of the Tetragonal Structure in a Hydrothermally
      Synthesized BaTiO3 Nanocrystal.
AB  - Higher OH concentration is identified in tetragonal barium titanate (BaTiO3)
      nanorods synthesized by a hydrothermal method with a 10 vol % ethylene glycol
      solvent (Inada, M.; et al. Ceram. Int. 2015, 41, 5581-5587). This is apparently
      inconsistent with the known fact that higher OH concentration in the conventional
      hydrothermal synthesis makes pseudocubic BaTiO3 nanocrystals more stable than the
      tetragonal one. To understand where and how the introduced OH anions are located
      and behave in the nanocrystals, we applied ab initio analysis to several possible
      microscopic geometries of OH locations, confirming the relative stability of the
      tetragonal distortion over the pseudocubic one because of the preference of trans
      type configurations of OH anions. We also performed Fourier transform infrared
      and X-ray diffraction analysis, all being consistent with the microscopic picture
      established by the ab initio geometrical optimizations.

PMID- 29658714
TI  - Activation of TRPV3 by Wood Smoke Particles and Roles in Pneumotoxicity.
AB  - Wood/biomass smoke particulate materials (WBSPM) are pneumotoxic, but the
      mechanisms by which these materials affect lung cells are not fully understood.
      We previously identified transient receptor potential (TRP) ankyrin-1 as a sensor
      for electrophiles in WBSPM and hypothesized that other TRP channels expressed by
      lung cells might also be activated by WBSPM, contributing to pneumotoxicity.
      Screening TRP channel activation by WBSPM using calcium flux assays revealed
      TRPV3 activation by materials obtained from burning multiple types of wood under
      fixed conditions. TRPV3 activation by WBSPM was dependent on the chemical
      composition, and the pattern of activation and chemical components of PM agonists
      was different from that of TRPA1. Chemical analysis of particle constituents by
      gas chromatography-mass spectrometry and principal component analysis indicated
      enrichment of cresol, ethylphenol, and xylenol analogues, plus several other
      chemicals among the most potent samples. 2,3-, 2,4-, 2,5-, 2,6-, 3,4-, and 3,5
      xylenol, 2-, 3-, and 4-ethylphenol, 2-methoxy-4-methylphenol, and 5,8
      dihydronaphthol were TRPV3 agonists exhibiting preferential activation versus
      TRPA1, M8, V1, and V4. The concentration of 2,3- and 3,4-xylenol in the most
      potent samples of pine and mesquite smoke PM (<3 MUm) was 0.1-0.3% by weight,
      while that of 5,8-dihydronaphthol was 0.03%. TRPV3 was expressed by several human
      lung epithelial cell lines, and both pine PM and pure chemical TRPV3 agonists
      found in WBSPM were more toxic to TRPV3-over-expressing cells via TRPV3
      activation. Finally, mice treated sub-acutely with pine particles exhibited an
      increase in sensitivity to inhaled methacholine involving TRPV3. In summary,
      TRPV3 is activated by specific chemicals in WBSPM, potentially contributing to
      the pneumotoxic properties of certain WBSPM.

PMID- 29658715
TI  - Accurate and Efficient Parallel Implementation of an Effective Linear-Scaling
      Direct Random Phase Approximation Method.
AB  - An efficient algorithm for calculating the random phase approximation (RPA)
      correlation energy is presented that is as accurate as the canonical molecular
      orbital resolution-of-the-identity RPA (RI-RPA) with the important advantage of
      an effective linear-scaling behavior (instead of quartic) for large systems due
      to a formulation in the local atomic orbital space. The high accuracy is achieved
      by utilizing optimized minimax integration schemes and the local Coulomb metric
      attenuated by the complementary error function for the RI approximation. The
      memory bottleneck of former atomic orbital (AO)-RI-RPA implementations (
      Schurkus, H. F.; Ochsenfeld, C. J. Chem. Phys. 2016 , 144 , 031101 and Luenser,
      A.; Schurkus, H. F.; Ochsenfeld, C. J. Chem. Theory Comput. 2017 , 13 , 1647 -
      1655 ) is addressed by precontraction of the large 3-center integral matrix with
      the Cholesky factors of the ground state density reducing the memory requirements
      of that matrix by a factor of [Formula: see text]. Furthermore, we present a
      parallel implementation of our method, which not only leads to faster RPA
      correlation energy calculations but also to a scalable decrease in memory
      requirements, opening the door for investigations of large molecules even on
      small- to medium-sized computing clusters. Although it is known that AO methods
      are highly efficient for extended systems, where sparsity allows for reaching the
      linear-scaling regime, we show that our work also extends the applicability when
      considering highly delocalized systems for which no linear scaling can be
      achieved. As an example, the interlayer distance of two covalent organic
      framework pore fragments (comprising 384 atoms in total) is analyzed.

PMID- 29658716
TI  - Effects of Substituents on the Aromatic Ring of Lignano-9,9'-lactone on Plant
      Growth Inhibitory Activity.
AB  - The relationship between the structure of lignano-9,9'-lactone (2,3
      dibenzylbutyrolactone) and its activity as a plant growth regulator has been
      clarified. Derivatives with higher plant growth inhibitory activity than natural
      dimethylmatairesinol 4 were synthesized. The 2-hydroxy-7- Z-ene derivative 42
      displayed growth inhibitory activity against both the shoots (IC50 = 0.65 mM) and
      roots (IC50 = 0.43 mM) of lettuce seedlings. Regiospecific activity was observed.
      The 2,3-dihydroxy derivative 24 showed the highest growth inhibitory activity
      against both the shoots (IC50 = 0.36 mM) and roots (IC50 = 0.13 mM) of Italian
      ryegrass seedlings. A similar level of activity to 24 against just the roots of
      Italian ryegrass seedlings was maintained when the hydroxy group at position 3 of
      the 2,3-dihydroxy derivative 24 was replaced by a fluorine atom. The (2-hydroxy,4
      fluoro)-derivative 33 also showed growth inhibitory activity against both the
      shoots (IC50 = 0.79 mM) and roots (IC50 = 0.14 mM) of Italian ryegrass seedlings.
      The level of activity was found to depend on the positions of the two hydroxy
      groups or the hydroxy group and fluorine atom on the aromatic ring. The
      importance of the lignano-9,9'-lactone structure was also shown.

PMID- 29658718
TI  - Metal-Controlled Switching of Enantioselectivity in the Mukaiyama-Michael
      Reaction of alpha,beta-Unsaturated 2-Acyl Imidazoles Catalyzed by Chiral Metal
      Pybox Complexes.
AB  - Metal-directed switching of enantioselectivity in the Mukaiyama-Michael reaction
      of silyl enol ethers to alpha,beta-unsaturated 2-acyl imidazoles using the same
      chiral indapybox ligand has been reported. The utility of this approach has been
      portrayed in the synthesis of both enantiomers of optically active delta-keto
      acid and ester as well as 3,4-dihydropyran-2-one. Moreover, enantioswitching in
      the construction of the tertiary stereocenter adjacent to a gem-dimethyl group
      has been achieved.

PMID- 29658707
TI  - Metal Catalysts for Heterogeneous Catalysis: From Single Atoms to Nanoclusters
      and Nanoparticles.
AB  - Metal species with different size (single atoms, nanoclusters, and nanoparticles)
      show different catalytic behavior for various heterogeneous catalytic reactions.
      It has been shown in the literature that many factors including the particle
      size, shape, chemical composition, metal-support interaction, and metal
      reactant/solvent interaction can have significant influences on the catalytic
      properties of metal catalysts. The recent developments of well-controlled
      synthesis methodologies and advanced characterization tools allow one to
      correlate the relationships at the molecular level. In this Review, the
      electronic and geometric structures of single atoms, nanoclusters, and
      nanoparticles will be discussed. Furthermore, we will summarize the catalytic
      applications of single atoms, nanoclusters, and nanoparticles for different types
      of reactions, including CO oxidation, selective oxidation, selective
      hydrogenation, organic reactions, electrocatalytic, and photocatalytic reactions.
      We will compare the results obtained from different systems and try to give a
      picture on how different types of metal species work in different reactions and
      give perspectives on the future directions toward better understanding of the
      catalytic behavior of different metal entities (single atoms, nanoclusters, and
      nanoparticles) in a unifying manner.

PMID- 29658717
TI  - Asymmetric Synthesis of Gonytolide A: Strategic Use of an Aryl Halide Blocking
      Group for Oxidative Coupling.
AB  - The first synthesis of the chromanone lactone dimer gonytolide A has been
      achieved employing vanadium(V)-mediated oxidative coupling of the monomer
      gonytolide C. An o-bromine blocking group strategy was employed to favor para-
      para coupling and to enable kinetic resolution of (+/-)-gonytolide C. Asymmetric
      conjugate reduction enabled practical kinetic resolution of a chiral, racemic
      precursor and the asymmetric synthesis of (+)-gonytolide A and its atropisomer.

PMID- 29658719
TI  - Treated Wastewater Changes the Export of Dissolved Inorganic Carbon and Its
      Isotopic Composition and Leads to Acidification in Coastal Oceans.
AB  - Human-induced changes in carbon fluxes across the land-ocean interface can
      influence the global carbon cycle, yet the impacts of rapid urbanization and
      establishment of wastewater treatment plants (WWTPs) on coastal ocean carbon
      cycles are poorly known. This is unacceptable as at present ~64% of global
      municipal wastewater is treated before discharge. Here, we report surface water
      dissolved inorganic carbon (DIC) and sedimentary organic carbon concentrations
      and their isotopic compositions in the rapidly urbanized Jiaozhou Bay in
      northeast China as well as carbonate parameters in effluents of three large WWTPs
      around the bay. Using DIC, delta13CDIC and total alkalinity (TA) data and a
      tracer model, we determine the contributions to DIC from wastewater DIC input,
      net ecosystem production, calcium carbonate precipitation, and CO2 outgassing.
      Our study shows that high-DIC and low-pH wastewater effluent represents an
      important source of DIC and acidification in coastal waters. In contrast to the
      traditional view of anthropogenic organic carbon export and degradation, we
      suggest that with the increase of wastewater discharge and treatment rates,
      wastewater DIC input may play an increasingly more important role in the coastal
      ocean carbon cycle.

PMID- 29658720
TI  - Adsorption Behavior of Lysozyme at Titanium Oxide-Water Interfaces.
AB  - We present an in situ X-ray reflectivity study of the adsorption behavior of the
      protein lysozyme on titanium oxide layers under variation of different
      thermodynamic parameters, such as temperature, hydrostatic pressure, and pH
      value. Moreover, by varying the layer thickness of the titanium oxide layer on a
      silicon wafer, changes in the adsorption behavior of lysozyme were studied. In
      total, we determined less adsorption on titanium oxide compared with silicon
      dioxide, while increasing the titanium oxide layer thickness causes stronger
      adsorption. Furthermore, the variation of temperature from 20 to 80  degrees C
      yields an increase in the amount of adsorbed lysozyme at the interface.
      Additional measurements with variation of the pH value of the system in a region
      between pH 2 and 12 show that the surface charge of both protein and titanium
      oxide has a crucial role in the adsorption process. Further pressure-dependent
      experiments between 50 and 5000 bar show a reduction of the amount of adsorbed
      lysozyme with increasing pressure.

PMID- 29658721
TI  - Interception of Secondary Amide Ylide with Sulfonamides: Catalyst-Controlled
      Synthesis of N-Sulfonylamidine Derivatives.
AB  - A novel, secondary amide activation strategy has been developed through the in
      situ generation of ylides from amides and diazoacetates. Under the developed
      reaction conditions, Mn-catalyzed ylide formation and interception reaction by
      sulfonamide delivered a variety of N-sulfonylamidines. Notably, when highly
      active Zn(OTf)2 was used as the catalyst, further N-H insertion products were
      obtained. In contrast with traditional methods, our amide activation strategy is
      distinguished by accessible starting material, inexpensive catalyst, and broad
      substrate scope.

PMID- 29658722
TI  - Evidence for cis Amide Bonds in Peptoid Nanosheets.
AB  - Peptoid nanosheets are supramolecular protein-mimetic materials that form from
      amphiphilic polypeptoids with aromatic and ionic side chains. Nanosheets have
      been studied at the nanometer scale, but the molecular structure has been
      difficult to probe. We report the use of 13C-13C dipolar recoupling solid-state
      NMR measurements to reveal the configuration of backbone amide bonds selected by
      13C isotopic labeling of adjacent alpha-carbons. Measurements on the same
      molecules in the amorphous state and in nanosheets revealed that amide bonds in
      the center of the amino block of peptoid (NaeNpe)7-(NceNpe)7 (B28) favor the
      trans configuration in the amorphous state and the cis configuration in the
      nanosheet. This unexpected result contrasts with previous NMR and theoretical
      studies of short solvated peptoids. Furthermore, examination of the amide bond at
      the junction of the two charged blocks within B28 revealed a mixture of both cis
      and trans configurational states, consistent with the previously predicted
      brickwork-like intermolecular organization.

PMID- 29658723
TI  - When fruits lose to animals: Disorganized search of semantic memory in
      Parkinson's disease.
AB  - OBJECTIVE: The semantic fluency task is widely used in both clinical and research
      settings to assess both the integrity of the semantic store and the effectiveness
      of the search through it. Our aim was to investigate whether nondemented
      Parkinson's disease (PD) patients show an impairment in the strategic exploration
      of the semantic store and whether the tested semantic category has an impact on
      multiple measures of performance. METHOD: We compared 74 nondemented PD patients
      with 254 healthy subjects in a semantic fluency test using relatively small
      (fruits) and large (animals) semantic categories. Number of words produced,
      number of explored semantic subcategories, and degree of order in the produced
      sequences were computed as dependent variables. RESULTS: PD patients produced
      fewer words than healthy subjects did, regardless of the category. Number of
      subcategories was also lower in PD patients than in healthy subjects, without a
      significant difference between categories. Critically, PD patients' sequences
      were less semantically organized than were those of controls, but this effect
      appeared in only the smaller category (fruits), thus pointing to a lack of
      strategy in exploring the semantic store. CONCLUSIONS: Our results show that the
      semantic fluency deficit in PD patients has a strategic component, even though
      that may not be the only cause of the impaired performance. Furthermore, our
      evidence suggests that the semantic category used in the test influences
      performance, hence providing an explanation for the failure by previous studies,
      which often used large categories such as animals, to detect strategy deficits in
      PD. (PsycINFO Database Record

PMID- 29658724
TI  - Sustaining prospective memory functioning in amnestic mild cognitive impairment:
      A lifespan approach to the critical role of encoding.
AB  - OBJECTIVE: Prospective memory (PM), the ability to remember to perform future
      activities, is a fundamental requirement for independent living. PM tasks pervade
      our daily lives, and PM failures represent one of the most prominent memory
      concerns across the entire life span. This study aimed to address this issue by
      exploring the potential benefits of specific encoding strategies on memory for
      intentions across healthy adulthood and in the early stages of cognitive
      impairment. METHOD: PM performance was explored through an experimental paradigm
      in 96 participants: 32 amnestic mild cognitively impaired patients aged 64-87
      years (M = 6.75, SD = 5.88), 32 healthy older adults aged 62-84 years (M = 76.06,
      SD = 6.03), and 32 younger adults 18-22 years (M = 19.75, SD = 1.16). The
      potential benefit of the use of enactment (i.e., physically simulating the
      intended action) at encoding to support an autonomous performance despite
      neuronal degeneration was assessed. RESULTS: PM was consistently identified as a
      sensitive and specific indicator of cognitive impairment. Importantly, enacted
      encoding was consistently beneficial for PM performance of all the participants,
      but especially so in the case of healthy and cognitively impaired older adults.
      These positive results have unveiled the potential of this encoding technique to
      optimize attentional demands through an adaptive allocation of strategic
      resources across both healthy and cognitively impaired samples. Theoretical
      implications of this work are discussed as well as the considerable translational
      potential to improve social well-being. CONCLUSIONS: A better understanding of
      the strategies that can enhance PM offers the potential for cost-effective and
      widely applicable tools which may support independent living across the adult
      life span. (PsycINFO Database Record

PMID- 29658725
TI  - I scan, therefore I decline: The time course of difficulty monitoring in humans
      (homo sapiens) and macaques (macaca mulatta).
AB  - The study of nonhumans' metacognitive judgments about trial difficulty has grown
      into an important comparative literature. However, the potential for associative
      learning confounds in this area has left room for behaviorist interpretations
      that are strongly asserted and hotly debated. This article considers how
      researchers may be able to observe animals' strategic cognitive processes more
      clearly by creating temporally extended problems within which associative cues
      are not always immediately available. We asked humans and rhesus macaques to
      commit to completing spatially extended mazes or to decline completing them
      through a trial-decline response. The mazes could sometimes be completed
      successfully, but other times had a constriction that blocked completion. A
      deliberate, systematic scanning process could preevaluate a maze and determine
      the appropriate response. Latency analyses charted the time course of the
      evaluative process. Both humans and macaques appeared, from the pattern of their
      latencies, to scan the mazes through before committing to completing them. Thus
      monkeys, too, can base trial-decline responses on temporally extended evaluation
      processes, confirming that those responses have strategic cognitive-processing
      bases in addition to behavioral-reactive bases. The results also show the value
      of temporally and spatially extended problems to let researchers study the
      trajectory of animals' online cognitive processes. (PsycINFO Database Record

PMID- 29658726
TI  - Factor structure and criterion validity across the full scale and ten short forms
      of the CES-D among Chinese adolescents.
AB  - We systematically examined the factor structure and criterion validity across the
      full scale and 10 short forms of the Center for Epidemiological Studies
      Depression Scale (CES-D) with Chinese youth. Participants were 5,434 Chinese
      adolescents in Grades 7 to 12 who completed the full CES-D; 612 of them further
      completed a structured diagnostic interview with the major depressive disorder
      (MDD) module of the Kiddie Schedule for Affective Disorder and Schizophrenia for
      School-age Children. Using a split-sample approach, a series of 4-, 3-, 2-, and 1
      factor models were tested using exploratory structural equation modeling and
      cross-validated using confirmatory factor analysis; the dimensionality was also
      evaluated by parallel analysis in conjunction with the scree test and aided by
      factor mixture analysis. The results indicated that a single-factor model of
      depression with a wording method factor fitted the data well, and was the optimal
      structure underlying the scores of the full and shortened CES-D. Additionally,
      receiver operating characteristic curve analyses for MDD case detection showed
      that the CES-D full-scale scores accurately detected MDD youth (area under the
      curve [AUC] = .84). Furthermore, the short-form scores produced comparable AUCs
      with the full scale (.82 to .85), as well as similar levels of sensitivity and
      specificity when using optimal cutoffs. These findings suggest that depression
      among Chinese adolescents can be adequately measured and screened for by a single
      factor structure underlying the CES-D scores, and that the short forms provide a
      viable alternative to the full instrument. (PsycINFO Database Record

PMID- 29658727
TI  - The influence of context in the subjective evaluation of "negative" alcohol
      related consequences.
AB  - College students may subjectively evaluate the consequences of drinking in
      unexpected ways, rating "negative" consequences as neutral or even positive
      experiences. We previously gathered qualitative evidence for several contextual
      factors that may influence one's subjective evaluations (e.g., social influences,
      intoxication level, concurrent positive consequences). The purpose of the present
      study was to quantitatively investigate whether student evaluations of
      consequences differ by various contextual factors. We administered an anonymous
      online survey to 214 college students (76% female, 69% drinkers, 48% heavy
      drinkers) in return for academic credit, on which they reported how positively or
      negatively they would evaluate 6 alcohol-related consequences (e.g., vomiting,
      being rude, blacking out) under different conditions. Paired samples t tests were
      used to compare evaluation ratings, averaged across consequences, under different
      hypothetical contextual conditions (e.g., among friends vs. strangers). Out of 16
      contextual comparisons, all but one (first-time vs. repeated consequence)
      revealed significant differences in subjective evaluations; the pattern held in
      reduced samples of just drinkers or just heavy drinkers. Examples include that
      consequences were viewed more negatively (a) if occurring at either a party or
      bar versus alone in one's home/dorm, (b) if friends express concern versus find
      it funny, (c) if the consequence was expected versus unexpected, and (d) if there
      are lasting consequences versus none. When using recent consequences in feedback
      based interventions to build motivation to change, it may be useful to discuss
      the context of a consequence and how this influences the perceived aversiveness
      of that consequence. (PsycINFO Database Record

PMID- 29658728
TI  - "Beyond sacrificial harm: A two-dimensional model of utilitarian psychology":
      Correction.
AB  - Reports an error in "Beyond Sacrificial Harm: A Two-Dimensional Model of
      Utilitarian Psychology" by Guy Kahane, Jim A. C. Everett, Brian D. Earp, Lucius
      Caviola, Nadira S. Faber, Molly J. Crockett and Julian Savulescu (Psychological
      Review, Advanced Online Publication, Dec 21, 2017, np). 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 presented in the erratum. All versions
      of this article have been corrected. (The following abstract of the original
      article appeared in record 2017-57422-001.) Recent research has relied on trolley
      type sacrificial moral dilemmas to study utilitarian versus nonutilitarian modes
      of moral decision-making. This research has generated important insights into
      people's attitudes toward instrumental harm-that is, the sacrifice of an
      individual to save a greater number. But this approach also has serious
      limitations. Most notably, it ignores the positive, altruistic core of
      utilitarianism, which is characterized by impartial concern for the well-being of
      everyone, whether near or far. Here, we develop, refine, and validate a new scale
      the Oxford Utilitarianism Scale-to dissociate individual differences in the
      'negative' (permissive attitude toward instrumental harm) and 'positive'
      (impartial concern for the greater good) dimensions of utilitarian thinking as
      manifested in the general population. We show that these are two independent
      dimensions of proto-utilitarian tendencies in the lay population, each exhibiting
      a distinct psychological profile. Empathic concern, identification with the whole
      of humanity, and concern for future generations were positively associated with
      impartial beneficence but negatively associated with instrumental harm; and
      although instrumental harm was associated with subclinical psychopathy, impartial
      beneficence was associated with higher religiosity. Importantly, although these
      two dimensions were independent in the lay population, they were closely
      associated in a sample of moral philosophers. Acknowledging this dissociation
      between the instrumental harm and impartial beneficence components of utilitarian
      thinking in ordinary people can clarify existing debates about the nature of
      moral psychology and its relation to moral philosophy as well as generate
      fruitful avenues for further research. (PsycINFO Database Record (c) 2018 APA,
      all rights reserved).

PMID- 29658729
TI  - A structural model of intrinsic motivation: On the psychology of means-ends
      fusion.
AB  - The term intrinsic motivation refers to an activity being seen as its own end.
      Accordingly, we conceptualize intrinsic motivation (IM) as (perceived) means-ends
      fusion and define an intrinsicality continuum reflecting the degree to which such
      fusion is experienced. Our means-ends fusion (MEF) theory assumes four major
      antecedents of activity-goal fusion: (a) repeated pairing of the activity and the
      goal, (b) uniqueness of the activity-goal connection, (c) perceived similarity
      between the activity and its goal, and (d) temporal immediacy of goal attainment
      following the activity. MEF theory further identifies two major consequences of
      the activity-goal fusion (i.e., manifestations of intrinsic motivation): (a)
      perceived instrumentality of the activity to goal attainment and consequent
      activity engagement, and (b) goal-related affective experience of the activity.
      Empirical evidence for MEF theory comes from diverse fields of psychological
      inquiry, including animal learning, brain research, and social cognition.
      (PsycINFO Database Record

PMID- 29658730
TI  - A dynamic dual process model of risky decision making.
AB  - Many phenomena in judgment and decision making are often attributed to the
      interaction of 2 systems of reasoning. Although these so-called dual process
      theories can explain many types of behavior, they are rarely formalized as
      mathematical or computational models. Rather, dual process models are typically
      verbal theories, which are difficult to conclusively evaluate or test. In the
      cases in which formal (i.e., mathematical) dual process models have been
      proposed, they have not been quantitatively fit to experimental data and are
      often silent when it comes to the timing of the 2 systems. In the current
      article, we present a dynamic dual process model framework of risky decision
      making that provides an account of the timing and interaction of the 2 systems
      and can explain both choice and response-time data. We outline several
      predictions of the model, including how changes in the timing of the 2 systems as
      well as time pressure can influence behavior. The framework also allows us to
      explore different assumptions about how preferences are constructed by the 2
      systems as well as the dynamic interaction of the 2 systems. In particular, we
      examine 3 different possible functional forms of the 2 systems and 2 possible
      ways the systems can interact (simultaneously or serially). We compare these dual
      process models with 2 single process models using risky decision making data from
      Guo, Trueblood, and Diederich (2017). Using this data, we find that 1 of the dual
      process models significantly outperforms the other models in accounting for both
      choices and response times. (PsycINFO Database Record

PMID- 29658731
TI  - Supporting and enhancing scientific rigor.
AB  - The purpose of this editorial is to provide an update on recent, ongoing, and new
      practices the Journal of Applied Psychology has implemented to further support
      and enhance scientific rigor. In line with the previous editorial, the practices
      discussed in the following text broadly seek to enhance scientific rigor and
      transparency in the empirical research published by providing the reader
      sufficient information needed to verify the accuracy and validity of study
      findings and inferences and enable the accumulation of knowledge through
      replications and extensions of primary research as well as meta-analyses.
      (PsycINFO Database Record

PMID- 29658732
TI  - When and how experienced incivility dissuades proactive performance: An
      integration of sociometer and self-identity orientation perspectives.
AB  - In this article we build on relational Sociometer Theory (Leary, 2005; Leary &
      Baumeister, 2000) to posit the impact of the belongingness threat of experienced
      incivility in one's work team on employee feelings of ostracism and subsequent
      engagement in proactive performance. Integrating the social-relational framework
      of Self-Identity Orientation Theory (Brewer & Gardner, 1996; Cooper & Thatcher,
      2010), we nuance our predictions by hypothesizing that chronic self
      identification orientations influence both the effect that experiencing
      incivility in one's work team exerts on feeling ostracized, and the impact that
      feeling ostracized has on subsequent employee proactive performance. Using a
      sample of 212 employees and their 51 supervising managers employed in an Internet
      service and solution company in China, we found support for our hypothesized
      model. Implications for theory and practice are discussed. (PsycINFO Database
      Record

PMID- 29658733
TI  - The paradox of agency: Feeling powerful reduces brokerage opportunity recognition
      yet increases willingness to broker.
AB  - Research suggests positions of brokerage in organizational networks provide many
      benefits, but studies tend to assume everyone is equally able to perceive and
      willing to act on brokerage opportunities. Here we challenge these assumptions in
      a direct investigation of whether people can perceive brokerage opportunities and
      are willing to broker. We propose that the psychological experience of power
      diminishes individuals' ability to perceive opportunities to broker between
      people who are not directly connected in their networks, yet enhances their
      willingness to broker. In Study 1, we find that employees in a marketing and
      media agency who had a high sense of power were likely to see fewer brokerage
      opportunities in their advice networks. In Study 2, we provide causal evidence
      for this claim in an experiment where the psychological experience of power is
      manipulated. Those who felt powerful, relative to those who felt little power,
      tended to see fewer brokerage opportunities than actually existed, yet were more
      willing to broker, irrespective of whether there was a brokerage opportunity
      present. Collectively, these findings present a paradox of agency: Individuals
      who experience power are likely to underperceive the very brokerage opportunities
      for which their sense of agency is suited. (PsycINFO Database Record

PMID- 29658734
TI  - Build or buy? The individual and unit-level performance of internally versus
      externally selected managers over time.
AB  - At some point, hiring managers in all organizations face the decision of whether
      to fill open positions with internal candidates (e.g., through promotions) or to
      hire external candidates (e.g., from competitors or new entrants into the labor
      market). Despite this ubiquitous choice, surprisingly little research has
      compared the effectiveness of internal and external selection or has identified
      situations in which 1 approach may be better than the other. The authors use
      theory on human capital resources to predict differences between internal and
      external hires on manager- and unit-level outcomes. Analysis of data from a quick
      service retail organization (N = 3,697) suggested that internally hired managers
      demonstrated higher levels of individual job performance and commanded lower
      starting salaries than externally hired managers. At the unit-level, operations
      led by internal hires demonstrated higher performance on organization-specific
      criteria (i.e., service performance), whereas no internal-external differences
      were found on more general criteria (i.e., financial performance). They also
      found some evidence that differences in unit service performance decreased over
      time (but did not diminish completely) as external hires improved at a slightly
      faster rate than internal hires. Overall, these findings underscore the
      complexity of the recurring "build or buy" decision. The results also suggest
      that internal hires generally outperform external hires, both individually and
      collectively, and they do so for less money. (PsycINFO Database Record

PMID- 29658735
TI  - Centralization of member voice in teams: Its effects on expertise utilization and
      team performance.
AB  - Voice, or the expression of work-related suggestions or opinions, can help teams
      access and utilize members' privately held knowledge and skills and improve
      collective outcomes. However, recent research has suggested that sometimes,
      rather than encourage positive outcomes for teams, voice from members can have
      detrimental consequences. Extending this research, we highlight why it is
      important to consider voice centralization within teams, or the extent to which
      voice is predominantly emanating from only a few members rather than equally
      spread across all members. We argue that, under certain circumstances, voice
      centralization is harmful to the utilization of members' expertise in the team
      and, thereby, to team performance. Specifically, we propose that voice
      centralization is likely to have negative effects when it occurs around members
      who are more socially dominant or are less reflective. We find support for our
      arguments in a sample of 78 teams (319 team members) working on graduate student
      projects in a business school over a semester. Overall, through our theory and
      results, we showcase why it is important for future studies to examine the
      distribution of voice among team members. (PsycINFO Database Record

PMID- 29658736
TI  - Seeing their side versus feeling their pain: Differential consequences of
      perspective-taking and empathy at work.
AB  - Perspective taking and empathic concern (empathy) have each been proposed as
      constructive approaches to social relationships. However, their potential
      distinctions, limitations, and consequences in task contexts are not well
      understood. We meta-analytically examined 304 independent samples to uncover
      unique effects of perspective taking and empathic concern on important work
      related outcomes. We develop and test a contingency model of those effects, based
      on three facets of psychological interdependence: outcome, hierarchical (or power
      asymmetry), and social category (or in-group/out-group distinctions). Results
      revealed perspective taking and empathic concern to have positive impacts on
      being supportive of others, but the effects of empathic concern were stronger. In
      contrast, perspective taking was an asset and empathy was a liability for
      capturing value in strategic interactions (e.g., negotiations). Effects of
      perspective taking and empathic concern were differentially contingent on
      psychological interdependence. The impact of perspective taking, but not of
      empathic concern, was attenuated or reversed under negative outcome
      interdependence; perspective-taking leads to advantage taking in competitive
      contexts. Perspective taking was particularly beneficial when the actor had high
      power, but empathic concern's benefits were independent of hierarchy. Finally,
      social dissimilarity had no detectable impact on the effects of perspective
      taking or empathic concern, contrary to our theorizing. Overall results suggest
      two key conclusions. First, perspective taking and empathic concern have powerful
      effects on work-related outcomes. Second, each construct has its own distinctive
      and predictable impacts. We conclude by offering practical suggestions for
      improving workplace interactions through perspective taking and empathic concern.
      (PsycINFO Database Record

PMID- 29658737
TI  - Negative beliefs about accepting coworker help: Implications for employee
      attitudes, job performance, and reputation.
AB  - For more than 30 years, researchers have investigated interpersonal helping in
      organizations, with much of this work focusing on understanding why employees
      help their colleagues. Although this is important, it is also critical that
      employees are willing to accept assistance that is offered by peers. Indeed,
      helping behavior should only enhance individual and organizational effectiveness
      if employees are actually willing to accept offers of assistance. Unfortunately,
      employees may sometimes have reservations about accepting help from their peers.
      In four studies, we examine the negative beliefs that employees have about
      accepting help from coworkers. In Study 1, we use inductive research to
      qualitatively understand why employees accept or decline coworker help. In Study
      2, we develop a preliminary, second-order reflective measure of negative beliefs
      about accepting coworker help that is indicated by the five specific (first
      order) reservations about accepting help identified in Study 1-diminished image,
      reciprocity obligation, self-reliance, coworker mistrust, and coworker
      incompetence. In Study 3, we refine our scale and demonstrate its convergent,
      discriminant, and criterion-related validity. Finally, in Study 4, we investigate
      the consequences of negative beliefs about accepting coworker help. We find that
      those who hold more negative beliefs are less likely to receive help from peers
      (and supervisors), report more negative job attitudes, and have lower levels of
      in-role performance, citizenship behavior, and creativity. Furthermore, employees
      with more negative beliefs about accepting help from coworkers are seen less
      favorably by their supervisors. Implications and future research directions are
      discussed. (PsycINFO Database Record

PMID- 29658738
TI  - "Revised scoring and improved reliability for the Communication Patterns
      Questionnaire": Correction to Crenshaw et al. (2017).
AB  - Reports an error in "Revised scoring and improved reliability for the
      Communication Patterns Questionnaire" by Alexander O. Crenshaw, Andrew
      Christensen, Donald H. Baucom, Norman B. Epstein and Brian R. W. Baucom
      (Psychological Assessment, 2017[Jul], Vol 29[7], 913-925). In the article, Table
      5 item content was incorrectly ordered. The corrected table is present in the
      erratum. (The following abstract of the original article appeared in record 2016
      43610-001.) The Communication Patterns Questionnaire (CPQ; Christensen, 1987) is
      a widely used self-report measure of couple communication behavior and is well
      validated for assessing the demand/withdraw interaction pattern, which is a
      robust predictor of poor relationship and individual outcomes (Schrodt, Witt, &
      Shimkowski, 2014). However, no studies have examined the CPQ's factor structure
      using analytic techniques sufficient by modern standards, nor have any studies
      replicated the factor structure using additional samples. Further, the current
      scoring system uses fewer than half of the total items for its 4 subscales,
      despite the existence of unused items that have content conceptually consistent
      with those subscales. These characteristics of the CPQ have likely contributed to
      findings that subscale scores are often troubled by suboptimal psychometric
      properties such as low internal reliability (e.g., Christensen, Eldridge, Catta
      Preta, Lim, & Santagata, 2006). The present study uses exploratory and
      confirmatory factor analyses on 4 samples to reexamine the factor structure of
      the CPQ to improve scale score reliability and to determine if including more
      items in the subscales is warranted. Results indicate that a 3-factor solution
      (constructive communication and 2 demand/withdraw scales) provides the best fit
      for the data. That factor structure was confirmed in the replication samples.
      Compared with the original scales, the revised scales include additional items
      that expand the conceptual range of the constructs, substantially improve
      reliability of scale scores, and demonstrate stronger associations with
      relationship satisfaction and sensitivity to change in therapy. Implications for
      research and treatment are discussed. (PsycINFO Database Record

PMID- 29658740
TI  - Twin classroom dilemma: To study together or separately?
AB  - There is little research to date on the academic implications of teaching twins
      in the same or different classroom. Consequently, it is not clear whether twin
      classroom separation is associated with positive or negative educational
      outcomes. As a result, parents and teachers have insufficient evidence to make a
      well-informed decision when twins start school. This study addresses two research
      questions: Are there average positive or negative effects of classroom
      separation? Are twins taught in different classes more different from each other
      than twins taught in the same class? Twin pairs from two large representative
      samples from Quebec (Canada) and the United Kingdom were evaluated across a large
      age range (7 to 16 years) on academic achievement, several cognitive abilities
      and motivational measures. Our results show almost no sizable positive or
      negative average effect of classroom separation on twins' achievement, cognitive
      ability and motivation. Twin pairs at age 12 (Quebec, Canada) and at age 16
      (United Kingdom) were slightly more similar on achievement if placed in the same
      classroom, with slightly greater similarity among monozygotic twins than
      dizygotic twins. However, the few effects found were weak, and it remains unclear
      whether they result from classroom separation or other factors. These results
      suggest that in terms of educational outcomes, policymakers should not impose
      rigid guidelines to separate twin pairs during their education. The choice of
      whether to educate twin pairs together or separately should be up to parents,
      twins and teachers, in response to twins' individual needs. (PsycINFO Database
      Record

PMID- 29658739
TI  - Child inhibitory control and maternal acculturation moderate effects of maternal
      parenting on Chinese American children's adjustment.
AB  - The goals of this study were to examine: (a) bidirectional associations between
      maternal parenting (physical punishment and guilt induction) and Chinese American
      preschool children's psychosocial adjustment and (b) the role of maternal
      cultural orientation and child temperament in moderating parenting effects.
      Participants were Chinese American mothers and children (N = 163, Mage = 4.56,
      53% boys). Mothers reported on their parenting practices at both Wave 1 (W1) and
      Wave 2 (W2) and their cultural orientations and children's inhibitory control at
      W1. Teachers rated children's prosocial, internalizing, and externalizing
      behaviors at both W1 and W2. A Bayesian approach to path analysis was utilized to
      investigate how parenting, child inhibitory control, and maternal cultural
      orientations work together to predict the development of children's prosociality
      and psychosocial problems. Results showed that for Chinese immigrant mothers who
      were highly acculturated toward the American culture and for children with low
      levels of inhibitory control, maternal use of physical punishment predicted more
      externalizing problems in children. Child inhibitory control and maternal
      enculturation were directly associated with less W2 child internalizing and
      externalizing behaviors. Moreover, physical punishment predicted more
      internalizing behavior, whereas guilt induction predicted less child
      internalizing behavior. Maternal guilt induction also prospectively predicted
      more prosocial behavior but only for children with low levels of inhibitory
      control. Finally, only one child effect was significant: More W1 internalizing
      behavior predicted less W2 physical punishment. These effects held after
      controlling for temporal stabilities of the constructs and demographic
      covariates. Findings are discussed within the cultural context of the study.
      (PsycINFO Database Record

PMID- 29658742
TI  - Child and contextual effects in the emergence of differential maternal
      sensitivity across siblings.
AB  - The present study examined the effects of socioeconomic status (SES) and sibling
      differences in birth weight on sibling differences in the receipt of maternal
      sensitivity (i.e., differential parenting). It was hypothesized that sibling
      differences in birth weight would predict absolute differential parenting across
      the sibship (i.e., the more different siblings' birth weight, the more different
      the level of sensitivity in the family, overall) and child-specific differential
      parenting (i.e., relatively heavier siblings receiving more sensitivity, compared
      to his or her counterpart within the family). It was also hypothesized that there
      would be greater sibling differences in birth weight in lower SES settings.
      Multiparous mothers were recruited within two weeks of childbirth and filmed
      interacting with each of their children when younger siblings were 1.60 years (SD
      = .16, N = 396 younger siblings) and next-older siblings were 4.05 (SD = .75; N =
      396 older siblings). Videotapes were coded for maternal sensitivity. Multilevel
      path-analysis revealed that lower-SES families exhibited greater sibling
      differences in birth weight, which corresponded to greater absolute differential
      parenting. Also, heavier siblings received relatively higher levels of
      sensitivity within the family. This study demonstrates that child and contextual
      factors operate together in predicting differential parenting. (PsycINFO Database
      Record

PMID- 29658741
TI  - Interparental hostility and children's externalizing symptoms: Attention to anger
      as a mediator.
AB  - This study examined children's attention biases to negative emotional stimuli as
      mediators of associations between interparental hostility and children's
      externalizing symptoms. Participants included 243 children (Mage = 4.60 years)
      and their parents and teachers across three annual measurement occasions. Cross
      lagged latent change analyses revealed that the association between interparental
      hostility and children's externalizing symptoms was mediated by children's
      attention to angry, but not sad or fearful, adult faces. Consistent with
      defensive exclusion models, the multimethod, multi-informant assessment of
      interparental hostility at Wave 1 specifically predicted decreases in children's
      attention to angry faces from Waves 1 to 2 in a visual search task. Declines in
      children's attention to anger, in turn, predicted increases in teacher reports of
      their externalizing problems across the three waves. Follow-up analyses further
      indicated that children's decreasing levels of emotional security in the
      interparental relationship were associated with the decreases in children's
      attention to angry stimuli. Results are discussed in relation to how they inform
      and advance information processing and social threat models in developmental
      psychopathology. (PsycINFO Database Record

PMID- 29658743
TI  - Which button will I press? Preference for correctly ordered counting sequences in
      18-month-olds.
AB  - Correct counting respects the stable order principle whereby the count terms are
      recited in a fixed order every time. The 4 experiments reported here tested
      whether precounting infants recognize and prefer correct stable-ordered counting.
      The authors introduced a novel preference paradigm in which infants could freely
      press two buttons to activate videos of counting events. In the "correct"
      counting video, number words were always recited in the canonical order ("1, 2,
      3, 4, 5, 6"). The "incorrect" counting video was identical except that the number
      words were recited in a random order (e.g., "5, 3, 1, 6, 4, 2"). In Experiment 1,
      18-month-olds (n = 21), but not 15-month-olds (n = 24), significantly preferred
      to press the button that activated correct counting events. Experiment 2 revealed
      that English-learning 18-month-olds' (n = 21) preference for stable-ordered
      counting disappeared when the counting was done in Japanese. By contrast,
      Experiment 3 showed that multilingual 18-month-olds (n = 24) preferred correct
      stable-ordered counting in an unfamiliar foreign language. In Experiment 4,
      multilingual 18-month-olds (N = 21) showed no preference for stable-ordered
      alphabet sequences, ruling out some alternative explanations for the Experiment 3
      results. Overall these findings are consistent with the idea that implicit
      recognition of the stable order principle of counting is acquired by 18 months of
      age, and that learning more than one language may accelerate infants'
      understanding of abstract counting principles. (PsycINFO Database Record

PMID- 29658744
TI  - When does cognitive decline begin? A systematic review of change point studies on
      accelerated decline in cognitive and neurological outcomes preceding mild
      cognitive impairment, dementia, and death.
AB  - Older adults who ultimately develop dementia experience accelerated cognitive
      decline long before diagnosis. A similar acceleration in cognitive decline occurs
      in the years before death as well. To evaluate preclinical and terminal cognitive
      decline, past researchers have incorporated change points in their analyses of
      longitudinal data, identifying point estimates of how many years prior to
      diagnosis or death that decline begins to accelerate. The current systematic
      review aimed to summarize the published literature on preclinical and terminal
      change points in relation to mild cognitive impairment (MCI), dementia, and
      death, identifying the order in which cognitive and neurological outcomes decline
      and factors that modify the onset and rate of decline. A systematic search
      protocol yielded 35 studies, describing 16 longitudinal cohorts, modeling change
      points for cognitive and neurological outcomes preceding MCI, dementia, or death.
      Change points for cognitive abilities ranged from 3-7 years prior to MCI
      diagnosis, 1-11 years prior to dementia diagnosis, and 3-15 years before death.
      No sequence of decline was observed preceding MCI or death, but the following
      sequence was tentatively accepted for Alzheimer's disease: verbal memory,
      visuospatial ability, executive functions and fluency, and last, verbal IQ. Some
      of the modifiers of the onset and rate of decline examined by previous
      researchers included gender, education, genetics, neuropathology, and
      personality. Change point analyses evidence accelerated decline preceding MCI,
      dementia, and death, but moderators of the onset and rate of decline remain
      ambiguous due to between-study modeling differences, and coordinated analyses may
      improve comparability across future studies. (PsycINFO Database Record

PMID- 29658745
TI  - Stability of genetic and environmental influences on executive functions in
      midlife.
AB  - Research on executive functions (EFs) has revealed that individual differences in
      general EF abilities are highly correlated across the first few decades of life,
      especially at the level of genetic influences. Our work has also provided
      evidence for substantial heritability of this Common EF factor in midlife, but it
      remains unclear whether individual differences in Common EFs continue to show
      strong stability in middle age. We examined data from 1,464 middle-aged twins
      from the Vietnam Era Twin Study of Aging, most of whom completed 7
      neuropsychological measures of EFs at 2 points in middle age (Mages = 56 and 62).
      Confirmatory factor analysis indicated that individual differences in Common EF,
      a latent factor explaining variation in seven neuropsychological EF tasks, were
      highly correlated across this 6-year period (r = .97), and that the same genetic
      and environmental influences were operating across this interval (genetic and
      shared environmental correlations = 1.0, nonshared environment correlation =
      .95). Similar phenotypic and genetic stability was observed for a Working Memory
      (WM)-Specific latent factor, which explained additional variance in working
      memory span tasks not captured by Common EF (r = .98, genetic correlation = 1.0,
      nonshared environmental correlation = .88). There was a large mean-level
      performance decline in Common EF (d = -.60) but not WM-Specific (d = -.03). These
      results suggest that there is substantial decline in Common EF abilities across
      middle age but that individual differences are almost perfectly stable. (PsycINFO
      Database Record

PMID- 29658747
TI  - Is subjective memory change in old age based on accurate monitoring of age
      related memory change? Evidence from two longitudinal studies.
AB  - Subjective memory change (SMC) in adulthood involves the perception that one's
      memory has declined from earlier levels of function. SMC has been conjectured to
      be more accurate than concurrent subjective memory because people use themselves
      as a standard of comparison. We used data from two longitudinal studies to
      contrast the accurate-monitoring-of-change hypothesis-actual memory change
      predicts SMC-against a constructed-judgment hypothesis that rated SMC is a
      function of rescaling concurrent memory beliefs without accessing actual memory
      change. It states that actual memory change has no predictive validity for SMC
      independent of concurrent memory beliefs. Data from both the Berlin Aging Study
      and the Health and Retirement Study (HRS) showed that older adults' current
      memory complaints strongly predicted current SMC, and that there was little
      relationship of longitudinally measured memory change to SMC, controlling on
      memory complaints. In the HRS there were reliable latent-growth-curve slope
      correlations of over .20 for change in episodic memory with both slopes of change
      in SMC and in memory complaints, yet little relationship of SMC slopes to
      episodic memory slopes, controlling on memory-complaint slopes. The results
      falsify the accurate-monitoring-of-change hypothesis regarding the origins of SMC
      in older adults. (PsycINFO Database Record

PMID- 29658746
TI  - Older adults show impaired modulation of attentional alpha oscillations: Evidence
      from dichotic listening.
AB  - Auditory attention is critical for selectively listening to speech from a single
      talker in a multitalker environment (e.g., Cherry, 1953). Listening in such
      situations is notoriously more difficult and more poorly encoded to long-term
      memory in older than in young adults (Tun, O'Kane, & Wingfield, 2002). Recent
      work by Payne, Rogers, Wingfield, and Sekuler (2017) in young adults demonstrated
      a neural correlate of auditory attention in the directed dichotic listening task
      (DDLT), where listeners attend to one ear while ignoring the other. Measured
      using electroencephalography, differences in alpha band power (8-14 Hz) between
      left and right hemisphere parietal regions mark the direction to which auditory
      attention is focused. Little prior research has been conducted on alpha power
      modulations in older adults, particularly with regard to auditory attention
      directed toward speech stimuli. In the current study, an older adult sample was
      administered the DDLT and delayed recognition procedures used by Payne et al.
      (2017). Compared to young adults, older adults showed reduced selective attention
      in the DDLT, evidenced by a higher rate of intrusions from the unattended ear.
      Moreover, older adults did not exhibit attention-related alpha modulation
      evidenced by young adults, nor did their event-related potentials (ERPs) to
      recognition probes differentiate between attended or unattended probes. Older
      adults' delayed recognition did not reveal a pattern of suppression of unattended
      items evidenced by young adults. These results serve as evidence for an age
      related decline in selective auditory attention, potentially mediated by age
      related decline in the ability to modulate alpha oscillations. (PsycINFO Database
      Record

PMID- 29658748
TI  - Cognitive ability does not predict objectively measured sedentary behavior:
      Evidence from three older cohorts.
AB  - Higher cognitive ability is associated with being more physically active. Much
      less is known about the associations between cognitive ability and sedentary
      behavior. Ours is the first study to examine whether historic and contemporaneous
      cognitive ability predicts objectively measured sedentary behavior in older age.
      Participants were drawn from 3 cohorts (Lothian Birth Cohort, 1936 [LBC1936] [n =
      271]; and 2 West of Scotland Twenty-07 cohorts: 1950s [n = 310] and 1930s [n =
      119]). Regression models were used to assess the associations between a range of
      cognitive tests measured at different points in the life course, with sedentary
      behavior in older age recorded over 7 days. Prior simple reaction time (RT) was
      significantly related to later sedentary time in the youngest, Twenty-07 1950s
      cohort (p = .04). The relationship was nonsignificant after controlling for long
      standing illness or employment status, or after correcting for multiple
      comparisons in the initial model. None of the cognitive measures were related to
      sedentary behavior in either of the 2 older cohorts (LBC1936, Twenty-07 1930s).
      There was no association between any of the cognitive tests and the number of sit
      to-stand transitions in any of the 3 cohorts. The meta-analytic estimates for the
      measures of simple and choice RT that were identical in all cohorts (n = 700)
      were also not significant. In conclusion, we found no evidence that objectively
      measured sedentary time in older adults is associated with measures of cognitive
      ability at different time points in life, including cognitive change from
      childhood to older age. (PsycINFO Database Record

PMID- 29658749
TI  - Age-related within-task adaptations in sequential decision making: Considering
      cognitive and motivational factors.
AB  - Many decisions require sequentially searching through the available alternatives.
      In these tasks, older adults have been shown to perform worse than younger
      adults, but the reasons why age differences occur are still unclear. In the
      present research, we tackle this question by investigating which strategies older
      and younger adults adopt and how these strategies relate to individual
      differences in cognitive (mental speed, working memory capacity) and motivational
      (need for cognitive closure) variables. To achieve this goal, we conducted two
      studies in which older and younger adults performed a computerized sequential
      choice task. Study 1 indicated that older adults changed their decision-making
      strategies throughout the task by reducing the number of options they considered.
      This change in strategy did not decrease performance because searching less
      allowed older adults to choose more promising options. In the second study we
      manipulated whether a long or short search was optimal. In the beginning older
      adults performed worse than younger adults independent of whether short or long
      search was adaptive. However, in the second half of the task we found age
      differences in performance when long search was required, but not when short
      search was required. In both studies whether or not older adults changed their
      strategy depended on their need for cognitive closure, suggesting that avoiding
      cognitive closure facilitates adaptive flexibility. Together, the two studies
      provide evidence for compensatory strategy adaptations among older adults
      completing sequential choice tasks. (PsycINFO Database Record

PMID- 29658750
TI  - Emotional arousal may increase susceptibility to fraud in older and younger
      adults.
AB  - Financial fraud is a societal problem for adults of all ages, but financial
      losses are especially damaging to older adults who typically live on fixed
      incomes and have less time to recoup losses. Persuasion tactics used by fraud
      perpetrators often elicit high levels of emotional arousal; thus, studying
      emotional arousal may help to identify the conditions under which individuals are
      particularly susceptible to fraud. We examined whether inducing high-arousal
      positive (HAP) and high-arousal negative (HAN) emotions increased susceptibility
      to fraud. Older (ages 65 to 85) and younger (ages 30 to 40) adults were randomly
      assigned to 1 of 3 emotional arousal conditions in a laboratory task: HAP, HAN,
      or low arousal (LA). Fraud susceptibility was assessed through participants'
      responses to misleading advertisements. Both HAP and HAN emotions were
      successfully induced in older and younger participants. For participants who
      exhibited the intended induced emotional arousal, both the HAP and HAN
      conditions, relative to the LA condition, significantly increased participants'
      reported intention to purchase falsely advertised items. These effects did not
      differ significantly between older and younger adults and were mitigated in
      participants who did not exhibit the intended emotional arousal. However,
      irrespective of the emotional arousal condition to which older adults were
      assigned (HAP, HAN, or LA), they reported greater purchase intention than did
      younger adults. These results inform the literature on fraud susceptibility and
      aging. Educating consumers to postpone financial decisions until they are in calm
      emotional states may protect against this common persuasion tactic. (PsycINFO
      Database Record

PMID- 29658752
TI  - Age-related changes in older adults' anger and sadness: The role of perceived
      control.
AB  - This longitudinal study examined the experience of sadness and anger in a sample
      of older adults. Based on the discrete emotion theory of affective aging, it was
      expected that sadness, but not anger, would increase in older adulthood over
      time. In addition, we hypothesized that inter- and intraindividual differences in
      low perceptions of control would be more strongly associated with sadness than
      anger. The 10-year study followed 187 community-dwelling older adults (Mage =
      72.25, SDage = 5.81). At each of six waves, participants' levels of sadness,
      anger, perceived control, and sociodemographic characteristics were assessed.
      Hierarchical linear modeling demonstrated that sadness, but not anger, linearly
      increased over time. These increases in sadness were evident only among older
      adults who reported low (but not high) levels of perceived control across the
      study period, and who experienced longitudinal declines (but not increases) in
      perceived control. In addition, nonlinear within-person reductions in perceived
      control predicted participants' sadness in the entire sample, but were associated
      with anger only in early, and not in advanced, old age. These findings support
      the discrete emotion theory of affective aging by documenting the distinctiveness
      of older adults' anger and sadness. These two negative emotions differ in terms
      of both age-related changes and predictive person-related perceptions of control.
      (PsycINFO Database Record

PMID- 29658751
TI  - Age differences in emotion regulation effort: Pupil response distinguishes
      reappraisal and distraction for older but not younger adults.
AB  - In previous research, older adults show greater emotional benefits from
      distracting themselves than from reappraising an event when strategically
      regulating emotion. Older adults also demonstrate an attentional preference to
      avoid, while younger adults show a bias toward approaching negative stimuli. This
      suggests a possible age-related differentiation of cognitive effort across
      approach and avoidance of negative stimuli during emotion regulation. In this
      study, we tracked cognitive effort via pupil dilation during the use of
      distraction (avoidance) and reappraisal (approach) strategies across age. Forty
      eight younger adults (M = 20.94, SD = 1.78; 19 men) and 48 older adults (M =
      68.82, SD = 5.40; 15 men) viewed a slideshow of negative images and were
      instructed to distract, reappraise, or passively view each image. Older adults
      showed greater pupil dilation during reappraisal than distraction, but younger
      adults displayed no difference between conditions-an effect that survived when
      controlling for gaze patterns. Gaze findings revealed that older adults looked
      less within images during active emotion regulation compared with passive viewing
      (no difference between distraction and reappraisal), and younger adults showed no
      difference across strategies. Younger adults gazed less within the most emotional
      image areas during distraction, but this did not significantly contribute to
      pupil response. Our findings support that distraction is less cognitively
      effortful than reinterpreting negative information in later life. These findings
      could be explained by older adults' motivational bias to disengage from negative
      information because of the age-related positivity effect, or compensation for
      decreased working memory resources across the life span. (PsycINFO Database
      Record

PMID- 29658753
TI  - Aging and attention to self-selected emotional content: A novel application of
      mobile eye tracking to the study of emotion regulation in adulthood and old age.
AB  - Previous studies of attentional deployment to a single stream of experimenter
      selected affective stimuli have found that compared to younger adults, older
      adults attend relatively more to positive and less to negative stimuli, and this
      can relate to better mood for them. Past studies of situation selection have
      yielded a contrasting picture of age similarity. In everyday life, attentional
      deployment is fundamentally and dynamically related to situation selection, but
      prior studies have investigated them only in isolation. We present new research
      using mobile eye tracking to test for age differences in selections of emotional
      stimuli and attention to self-selected choices after a negative mood induction.
      Younger, middle-aged, and older individuals (N = 150) were either instructed to
      specifically try to regulate their mood state or not before having their
      selections, attention, and mood recorded. We used a database-oriented method to
      analyze fixations to positive, negative, and neutral videos once selected.
      Findings suggested more similarities than differences among age groups in what
      material was selected, how participants attended to selected material, and how
      their choices and attention predicted mood. Situation selection also had a more
      consistent relationship with mood than attentional deployment. These results
      suggest that age differences in attention are less apparent when participants
      have flexibility to avoid and choose stimuli than when viewing a predetermined
      fixed set of stimuli. Thus, emotion regulation strategies of selection and
      attention may show more age similarities when they interact than when studied in
      isolation. (PsycINFO Database Record

PMID- 29658754
TI  - Family rituals in pediatric epilepsy: Links to parental competence and
      adaptation.
AB  - This cross-sectional study examined the associations between family ritual
      meaning and 3 indicators of parental adaptation (anxious and depressive symptoms
      and quality of life) via 2 dimensions of parental competence-satisfaction and
      efficacy-in parents of children with epilepsy. Two hundred Portuguese parents of
      children diagnosed with epilepsy for at least 6 months completed self-report
      measures assessing the main study variables. Our results showed that when parents
      reported stronger family ritual meaning, they also reported higher levels of
      parental satisfaction and efficacy, which were in turn were associated with lower
      psychological distress (anxious and depressive symptoms) and better quality of
      life of parents. This pattern of results was significant regardless of the
      severity of children's epilepsy, age group, and family socioeconomic level. In
      the context of pediatric epilepsy, empirical evidence was found for the role of
      family ritual meaning in being directly and indirectly associated with parents'
      adaptation outcomes by higher levels of parental satisfaction and efficacy.
      Focusing intervention targets on what families naturally do and recognize as
      their own ritual meaning may be a favorable route to address those at risk of
      psychological distress and lower quality of life. (PsycINFO Database Record

PMID- 29658755
TI  - Interparental conflict and long-term adolescent substance use trajectories: The
      role of adolescent threat appraisals.
AB  - Although interparental conflict (IPC) has been linked directly and indirectly
      (via adolescents' appraisals) with a wide range of adolescent outcomes, little is
      known about the implications of IPC and related adolescent threat appraisals for
      substance use. Drawing on the cognitive-contextual framework, we test competing
      hypotheses about how IPC may impact adolescent substance use outcomes,
      specifically testing whether (a) threat appraisals are directly related to
      escalation in alcohol and tobacco use over adolescence, or (b) threat appraisals
      are indirectly associated with substance use through their impact on adolescent
      internalizing problems. Family data from 768 2-caregiver families were analyzed
      for this study. Adolescents (53% female) were followed on 7 occasions starting in
      the fall of 6th grade (mean age = 11.3 years) through the spring of 11th grade.
      IPC and family demographic data were collected from parents. Youth provided data
      on their appraisals of conflict, internalizing problems, and substance use. Using
      longitudinal growth curve models, findings supported threat appraisals as a
      direct risk factor for escalating cigarette use, but not escalating alcohol use,
      during adolescence. In the alcohol trajectory model, IPC was a direct predictor
      of increases in alcohol use over time. These findings indicate that high levels
      of threat appraisals are a specific and direct risk for greater increases in
      cigarette use over the course of adolescence and that IPC confers risk for
      increasing rates of alcohol use over adolescence. (PsycINFO Database Record

PMID- 29658756
TI  - Stress spillover, African Americans' couple and health outcomes, and the stress
      buffering effect of family-centered prevention.
AB  - This study investigated (a) the stress spillover pathways linking contextual
      stressors, changes in couple relationship functioning and depressive symptoms,
      and changes in individuals' physical health, and (b) the stress-buffering effect
      of participation in an efficacious, family centered prevention program designed
      to protect couples from the deleterious effects of stressors. The sample
      consisted of 346 rural African American couples (63% married) who participated in
      a randomized controlled trial of the Protecting Strong African American Families
      (ProSAAF) program. Participants were assessed at three time points across 17
      months. Results examining stress spillover within the control group indicated
      that elevated current, but not prior, financial hardship was associated with
      decreased effective communication, relationship satisfaction, and relationship
      confidence as well as increased depressive symptoms; current levels of racial
      discrimination also predicted greater depressive symptoms. Relationship
      confidence and relationship satisfaction, but not communication or depressive
      symptoms, in turn predicted declines in self-reported physical health. Results
      examining stress-buffering effects suggested that participation in ProSAAF
      protected individuals' relationship confidence from declines associated with
      elevated financial hardship. In addition, the indirect effect linking financial
      hardship to declines in physical health through relationship confidence that
      emerged among participants in the control group was no longer evident for ProSAAF
      couples. Results highlight the effect of contextual stressors on African
      Americans' couple and individual well-being and the potential for the ProSAAF
      program to provide a constructed resilience resource, protecting couple's
      confidence in their relationship from the negative effects of financial hardship
      and, consequently, promoting physical health. (PsycINFO Database Record

PMID- 29658757
TI  - Adult adiposity linked to relationship hostility for low-cortisol reactors.
AB  - Past research on the relation between hostility in intimate relationships and
      adiposity has yielded mixed findings. The present study investigated whether the
      association between relationship hostility and adiposity is moderated by people's
      biological reactions to couple conflict. Cohabiting adult couples (N = 117
      couples) engaged in two conflict interactions, before and after which salivary
      cortisol levels were measured. Results revealed an association between
      relationship hostility and adiposity, but this association was concentrated among
      people with relatively low levels of cortisol reactivity to couple conflict.
      Results are interpreted in light of research demonstrating that cortisol
      reactivity can become blunted over time in response to repeated stressors. These
      results provide precision to etiological models of obesity by identifying
      cortisol reactivity as a factor that moderates the association between
      relationship hostility and adiposity. (PsycINFO Database Record

PMID- 29658758
TI  - Coparenting in the family of origin and new parents' couple relationship
      functioning.
AB  - To better understand the long-term implications of coparenting quality for adult
      child outcomes, we examined the associations between coparenting quality in the
      family of origin (Generation 1; G1), and attachment avoidance and anxiety and
      perceived relationship functioning of new parents (Generation 2; G2) using a
      dyadic approach. Dual-earner families expecting their first child (n = 182) were
      followed across the transition to parenthood and assessed at the third trimester
      of pregnancy (3T) and 9 months after childbirth (9M). At 3T, parents reported on
      the coparenting quality in their families of origin, and attachment avoidance and
      anxiety. At 9M, the participants reported their perceptions of couple
      relationship functioning-dyadic adjustment and negative interaction. We found
      that at 9M, G1's coparenting quality predicted not only G2's own perceptions but
      also G2's partners' perceptions of relationship functioning. Further, mediational
      analyses showed that parents' G1 coparenting quality was associated with higher
      G2 self- and partner-perceived dyadic adjustment and lower G2 self-perceived
      negative interaction through G2 parents' lower attachment anxiety and avoidance.
      G1 coparenting quality was negatively associated with G2 partner-perceived
      negative interaction through G2 parents' lower attachment anxiety. Our findings
      suggest that coparenting relationships have long-term implications for human
      development even into adulthood. (PsycINFO Database Record

PMID- 29658759
TI  - Parent contributions to friendship stability during the primary school years.
AB  - The present study examines whether characteristics of parents predict the
      stability of a child's best friendships across the primary school years.
      Participants included 1,523 Finnish children (766 boys) who reported involvement
      in a total of 1,326 reciprocated friendship dyads in the 1st grade (M = 7.16
      years old). At the onset of the study, mothers and fathers completed
      questionnaires describing their own parenting (i.e., behavioral control,
      psychological control, and affection toward the child) and depressive symptoms.
      Child scores for peer status (i.e., acceptance and rejection) were derived from
      1st grade peer nomination data. Discrete-time survival analyses predicted the
      occurrence and timing of friendship dissolution, across 1st to 6th grades, for
      friendships that began in 1st grade. Parent depression and parent psychological
      control uniquely predicted subsequent child friendship dissolution, above and
      beyond the contribution of peer status variables. (PsycINFO Database Record

PMID- 29658762
TI  - Relationships with former stepgrandparents after remarriage dissolution.
AB  - Increases in stepfamily formation and longevity suggest that more children have
      stepgrandparent relationships than ever before. Because remarriages end in
      divorce more often than first marriages, many children experience the involuntary
      dissolution of stepgrandparent ties. Little is known about stepgrandparent
      relationships in general, and even less is known about how these relationships
      are affected by remarriage dissolution. Guided by symbolic interaction theory,
      the purpose of this study was to understand how stepgrandchildren make sense of
      their relationships with former stepgrandparents. We explored their perceptions
      of why relationships were or were not maintained and the impact of continued or
      dissolved ties on their personal well-being. Former stepgrandchildren (N = 29)
      aged 18 to 37 were interviewed about their former stepgrandparents. The quality
      and continuity of these relationships were contingent on stepgrandchildren's
      relationships with former stepparents, biological parents' relationships with
      former stepgrandparents, and efforts by former stepgrandparents to remain
      involved. Losing ties with former stepgrandparents was upsetting, especially when
      relationships with biological grandparents were not close. Individuals who
      maintained relationships with former stepgrandparents benefitted from continued
      access to valuable resources (e.g., positive role models, additional sources of
      love and support). Our findings have important implications for clinicians' and
      researchers' understanding of the effects of remarriage dissolution on children
      as well as the intergenerational efforts that may be critical for preserving
      meaningful stepfamily ties. (PsycINFO Database Record

PMID- 29658760
TI  - Child internalizing problems and mother-child discrepancies in maternal
      rejection: Evidence for bidirectional associations.
AB  - We investigated the bidirectional associations between mother-child discrepancies
      in their perceptions of maternal rejection and children's internalizing problems
      over 10 years from pre/early adolescence to early adulthood. Mothers' reports of
      rejection and involvement in the parent-child relationship, the children's
      perception of the mother's rejection, and children's self-report of internalizing
      problems were collected from a sample of 360 low-income ethnically diverse urban
      mother-child dyads at three time points (T1, T2, and T3) with 5-year intervals.
      Children were on average 12.6 years old at T1 (54% girls). Using a series of
      nested path analyses, we found that mother-child discrepancies while reporting
      maternal rejection at T1 were predictive of lower ratings of maternal involvement
      at T2 (beta = -.14), which predicted higher levels of internalizing problems at
      T3 (beta = -.16). The presence of mother's affective disorder was related to T1
      mother-child discrepancies (beta = .14). Regarding bidirectional associations,
      children's internalizing problems predicted maternal involvement across all time
      points, whereas T2 maternal involvement predicted T3 child internalizing
      problems. Discrepancies showed small associations with child internalizing
      problems both concurrently and over time. The findings highlight the importance
      of early discrepancies in the perception of maternal rejection for child
      internalizing symptoms. (PsycINFO Database Record

PMID- 29658763
TI  - The Birth Experiences Questionnaire: A brief measure assessing psychosocial
      dimensions of childbirth.
AB  - Childbirth is an important life event that has been understudied by
      psychologists. Parents may find birth to be stressful, painful, and frightening,
      or feel supported and calm. Birth experiences can be shaped both by preexisting
      psychological vulnerabilities and by medical events that occur during childbirth.
      The birth experience may influence both parent and child well-being, helping to
      shape the health of the new family. This paper introduces the Birth Experiences
      Questionnaire (BEQ), a brief 10-item measure designed to assess stress, fear, and
      partner support during birth. We administered the BEQ to 51 couples (102 parents)
      within 1-2 days of their child's birth. Categorical principal component analysis
      was used to test reliability and factor structure. The BEQ showed good
      reliability (Cronbach's alpha = .81 for mothers, 0.80 for fathers) and internal
      consistency, suggesting it is acceptable for use as a unifactorial measure. The
      most variability was explained by a 3-factor solution, with the 3 factors
      reflecting Stress, Support, and Fear for mothers and Stress, Support, and
      Violation of Expectations for fathers. Prenatally assessed stress, depression,
      pregnancy-specific anxiety, and social support were all predictive of parents'
      BEQ scores. BEQ scores were also associated with infant Apgar scores and with
      couples' negative emotion word usage during an open-ended birth narrative. The
      BEQ differentiated between parents who had more medically complex births (e.g.,
      labor induction, complications, and C-section delivery) versus less complex
      births. In conclusion, the BEQ can be administered shortly after birth to both
      parents, and may capture important dimensions of the perinatal experience.
      (PsycINFO Database Record

PMID- 29658761
TI  - Longitudinal associations of maternal depression and adolescents' depression and
      behaviors: Moderation by maltreatment and sex.
AB  - This study explored the longitudinal relationships among maternal depressive
      symptoms, children's depressive symptoms, aggression, and rule breaking and
      tested the moderating effects of maltreatment and child sex. A sample of 175
      biological mother-child dyads (86 maltreated and 89 comparison) were seen at
      three time points, beginning at an average child age of 10.87 years. Results from
      cross-lagged models showed maternal depressive symptoms were related to higher
      levels of children's depressive symptoms but not children's aggression or rule
      breaking. Rule breaking predicted maternal depressive symptoms only in the
      comparison group. Child sex moderated some relationships. Boys' depression
      predicted maternal depressive symptoms, whereas maternal depressive symptoms
      predicted aggression among girls. There was no evidence in this sample that child
      maltreatment increased the effects of maternal depressive symptoms on child
      outcomes. These results suggest that attention in clinical practice to the
      importance of addressing maternal depression as well as addressing children's
      functioning should continue into adolescence. (PsycINFO Database Record

PMID- 29658764
TI  - A randomized controlled trial comparing family mediation with and without
      motivational interviewing.
AB  - Family mediation is a widely used approach to assist separated parents to resolve
      conflicts about parenting arrangements for their children, yet frequently parents
      undertaking mediation do not reach a mutually agreeable resolution. In Australia,
      where the current study was conducted, separated parents must attempt family
      mediation before they can seek to appear in the family court for custody issues.
      We compared mediation enhanced with motivational interviewing (MI) with mediation
      as usual (MAU) in a randomized controlled trial. One hundred and seventy-seven
      separated-parent dyads were recruited from a community-based telephone mediation
      service, and randomized to receive MI or MAU. Outcome of mediation was classified
      as no agreement, partial agreement on some of the areas in dispute, and full
      agreement. We assessed parental psychological distress, emotional attachment to
      former partner by the coparent, child adjustment, and coparental conflict before
      and after the mediation, and at 3-month follow-up. MI had double the rate of full
      agreements of MAU (33% vs. 16%), and a lower rate of no agreement than MAU
      parents (33% vs. 42%). Psychological distress, coparental conflict and attachment
      to the former partner declined from pre- to postmediation in both conditions, but
      child adjustment was unchanged. There was no difference between MAU and MI on any
      of these outcomes. MI enhanced achievement of agreements but did not enhance
      other outcomes. Conducting the study in a busy community mediation service
      created some challenges that compromised implementation of the study which might
      influence the reliability of findings. However, the possibility that MI enhances
      agreement in mediation warrants further investigation. (PsycINFO Database Record

PMID- 29658765
TI  - Premarital education and later relationship help-seeking.
AB  - Despite evidence that empirically supported couple therapies improve marital
      relationships, relatively few couples seek help when they need it. Low-income
      couples are particularly unlikely to engage in relationship interventions despite
      being at greater risk for distress and dissolution than their higher-income
      counterparts. The present study aimed to clarify how premarital education
      influences couples' progression through different stages of later help-seeking,
      as identified in prior research. Using 5 waves of self-report data from a sample
      of 431 ethnically diverse newlywed couples living in low-income neighborhoods,
      analyses revealed that wives who received premarital education later considered
      seeking therapy at a higher level of relationship satisfaction and lower level of
      problem severity than those who did not receive premarital education, though this
      was not true for husbands. Wives who received premarital education were also more
      likely as newlyweds to say that they would seek therapy if their relationship was
      in trouble, though husbands were not. Spouses who considered seeking therapy were
      more likely to follow through with participation if they had received premarital
      education, whereas if they had not received premarital education they were more
      likely to consider seeking therapy without following through. Similarly, among
      couples who received therapy, those who also received premarital education sought
      therapy earlier than those who did not receive premarital education, though not
      at a higher level of relationship satisfaction. Taken together, these results
      suggest that participation in premarital education is linked with later help
      seeking by empowering couples to take steps throughout their marriage to maintain
      their relationship. (PsycINFO Database Record

PMID- 29658766
TI  - (Why) do victims become perpetrators? Intergenerational transmission of parental
      violence in a representative German sample.
AB  - Child maltreatment can severely impair children's emotional and physical well
      being as well as their individual development across the life span. In 2011, the
      Criminological Research Institute of Lower Saxony (Germany), conducted a
      nationally representative victim survey on diverse forms of victimizations (N =
      11,428). Among other things, experienced and exerted parental violence as well as
      participants' knowledge regarding the abolition of the parental right of corporal
      punishment were assessed. Apart from providing current estimates of the
      prevalence of experienced and exerted parental violence in Germany, we identified
      specific risk markers for the intergenerational transmission of parental
      violence. In summary, 52.6% of the participants reported experiences of at least
      one incident of at least minor parental violence until the age of 16 years, and
      22.9% had exerted at least once at least one act of minor violence against their
      own children. Nonparametric conditional inference tree analyses revealed
      experienced parental violence as the most important risk marker for exerting
      parental violence. Furthermore, the number of children currently cared for,
      parental age, and origin as well as knowledge about the current legal situation
      regarding corporal punishment were significantly associated with exerting
      parental violence. For individuals without a history of parental violence, lack
      of experienced parental warmth and an age between 33 and 40 years increased the
      risk of exerting parental violence. The results are discussed in terms of their
      implications for designing effective prevention and intervention strategies.
      (PsycINFO Database Record

PMID- 29658767
TI  - Quality indicators in colonoscopy. The colonoscopy procedure.
AB  - The aim of the project this paper is part of was to propose quality and safety
      procedures and indicators to facilitate quality improvement in digestive
      endoscopy units. In this second issue, procedures and indicators are suggested
      regarding colonoscopy. First, a diagram charting the previous and subsequent
      steps of colonoscopy was designed. A group of experts in health care quality
      and/or endoscopy, under the auspices of the Sociedad Espanola de Patologia
      Digestiva (SEPD), performed a qualitative review of the literature regarding
      colonoscopy-related quality indicators. Subsequently, using a paired-analysis
      method, the aforementioned literature was selected and analyzed. A total of 13
      specific indicators were found aside of the common markers elsewhere described,
      ten of which are process-related (one pre-procedure, seven procedure, and two
      post-procedure markers) while the remaining three are outcome-related. Quality of
      evidence was assessed for each one of them using the GRADE (Grading of
      Recommendations Assessment, Development and Evaluation) classification.

PMID- 29658768
TI  - Idiopathic portal hypertension with regard to thiopurine treatment.
AB  - Idiopathic portal hypertension (IPH) is an infrequent adverse reaction to the use
      of thiopurines that tends to be overlooked. Herein, we present a patient with
      ileocolic Crohn's disease treated with azathioprine who presented ascites,
      esophageal varices and splenomegaly without any signs of liver cirrhosis. A
      portal hemodynamics study revealed a normal portosystemic gradient compatible
      with presinusoidal portal hypertension. Finally, IPH was diagnosed after a liver
      biopsy. IPH secondary to thiopurines is due to a 6-thioguanine nucleotide (6-TGN)
      dependent reaction and occurs predominantly between three months and three years
      after the start of treatment. The onset is usually insidious and thrombocytopenia
      is the first manifestation. The definitive diagnosis is obtained by liver biopsy.

PMID- 29658770
TI  - The new mandate and work of ICRP Committee 4.
AB  - Committee 4 of the International Commission on Radiological Protection (ICRP) is
      charged with the development of principles and recommendations on radiological
      protection of people and the environment in all exposure situations. For the term
      beginning in July 2017, the Committee has a total of 18 members from 12
      countries. The programme of work includes a wide range of activities in five
      major thematic areas. The first is the consolidation and preparation of reports
      elaborating application of the system of protection in existing exposure
      situations. Second is the continuation of work on emergency exposure situations,
      and ICRP updates to recommendations in light of the accident at Fukushima Daiichi
      nuclear power plant. Third is examination of fundamentals of protection
      recommendations, including the ethical principles underlying the recommendations
      and application of those principles in practical decision making. Fourth is the
      new area of integration of protection of the environment into the system of
      protection. Finally, Committee 4 continues work to prepare specific topical
      reports on subjects in which additional information is useful to understand and
      apply the Commission's recommendations in particular circumstances.

PMID- 29658769
TI  - Multimodality imaging assessment of endoleaks post-endovascular aortic repair.
AB  - Endoleaks are a common complication of endovascular aortic repair (EVAR). As a
      result, patients require lifelong imaging surveillance following EVAR. In current
      clinical practice, evaluation for endoleaks is predominantly performed with CT
      angiography (CTA). Due to the significant cumulative radiation burden associated
      with repetitive CTA imaging, as well as the repeated administration of
      nephrotoxic contrast agent, contrast-enhanced ultrasound (CEUS) and magnetic
      resonance angiography (MRA) have evolved as potential modalities for lifelong
      surveillance post-EVAR. In this paper, multimodality imaging, including CTA, CEUS
      and MRA, for the surveillance of endoleaks is discussed. Further, new CTA
      techniques for radiation reduction are elaborated. Additionally, imagery for
      three cases of aortic endoleak detection using CTA and five cases using MRA are
      presented. Imaging for different types of endoleaks with CTA, MRA and CEUS are
      presented. For lifelong endoleak surveillance post-EVAR, CTA is still regarded as
      the imaging modality of choice. However, advancements in CEUS and MRA technique
      enable partial replacement of CTA in certain patients.

PMID- 29658771
TI  - Diagnostic performances of superb microvascular imaging, shear wave elastography
      and shape index in pediatric lymph nodes categorization: a comparative study.
AB  - OBJECTIVE: To determine the diagnostic utility of a vascularity index via superb
      microvascular imaging in lymph nodes of children with malignant lymphoma and
      acute lymphadenitis compared to normal lymph nodes. METHODS: We performed a
      retrospective study for multiparametric lymph node (LN) evaluation. Malignant
      lymphoma diagnosed via histopathological examination and lymph nodes receiving an
      acute lymphadenitis diagnosis based on clinical and laboratory findings
      constituted the study subgroups. We calculated a shape index [SI (percent of
      shortest to longest diameter)] using grayscale ultrasonography and elasticity and
      velocity values via shear wave elastography (SWE) as well as a vascularity index
      (VI) using superb microvascular imaging (SMI) for comparison with normal lymph
      nodes. RESULTS: 45 lymph nodes diagnosed with malignant lymphoma, 72 lymph nodes
      diagnosed with acute lymphadenitis and 146 normal lymph nodes were evaluated. For
      differentiating lymphoma from normal lymph nodes, vascularity index cut-off
      values higher than 15% represented a diagnostic accuracy of 95%; cut-off
      elasticity values higher than 17 kPa exhibited a diagnostic accuracy of 99%.
      Optimal VI, elasticity, velocity and SI cut-off values in differentiating
      lymphoma from lymphadenitis were 15%, 17 kPa, 2.45 m sn-1 (p < 0.001) and 65% (p
      < 0.002) with calculated diagnostic accuracies of 83, 87, 88 and 68%,
      respectively. CONCLUSION: Vascularity index values obtained via superb
      microvascular imaging and SWE would be reasonably useful in differentiating
      malignant lymphoma and acute lymphadenitis from normal LNs. SWE would be more
      efficient in distinguishing malignant lymph nodes from acute lymphadenitis
      compared with superb microvascular imaging. Advances in knowledge: Vascularity
      index by superb microvascular imaging would be a novel Doppler parameter in
      differentiating both lymphoma from lymphadenitis and also lymphadenitis from
      normal lymph nodes.

PMID- 29658773
TI  - How Tapping into "Energy" Can Trigger a Paradigm Shift in Biomedicine.

PMID- 29658772
TI  - The role of ketogenic diets in the therapeutic management of adult and paediatric
      gliomas: a systematic review.
AB  - AIM: We performed a systematic review of the evidence for effectiveness and
      acceptability of different ketogenic diets (KDs) in the therapeutic management of
      gliomas. METHODS: The search strategy included searches of seven electronic
      databases. Data extraction and quality assessment were undertaken independently
      by two authors. RESULTS: No randomized clinical trials were identified. Six
      studies (n = 39) met the eligibility criteria for this review - all were case
      series or reports and therefore at high risk of bias. All studies reported
      overall or progression-free survival; however the effectiveness of KD
      interventions could not be established. Dietary acceptability was not reported.
      CONCLUSION: The effectiveness and acceptability of KDs in the management of
      gliomas is unknown and high quality randomized controlled trials are needed.

PMID- 29658774
TI  - A Simple Linear Space Algorithm for Computing Nonoverlapping Inversion and
      Transposition Distance in Quadratic Average Time.
AB  - In the sequence alignment problem, it is important to compare DNA sequences to
      retrieve relevant information and align these sequences. An inversion and a
      translocation are important operations in comparing DNA sequences in biosequence
      analysis. The alignment problem with nonoverlapping inversions and translocations
      is to find an alignment with nonoverlapping inversions and translocations for the
      given two strings X and Y. This problem has interesting application for finding a
      common sequence from two mutated sequences. A linear space and quadratic average
      time algorithm to compute the mutation distance between two strings of the same
      length under nonoverlapping inversions and transpositions is presented in this
      article. The recursive formula for this purpose is novel to the best of our
      knowledge. The space costs of the algorithms to solve the same problem are
      typically quadratic, and thus, our original algorithm is the first linear space
      algorithm to solve the mutation distance problem.

PMID- 29658775
TI  - Altering allergenicity of cow's milk by food processing for applications in
      infant formula.
AB  - Cow's milk-based infant formulas have a long tradition in infant nutrition,
      although some infants are unable to use them due to presence of several known
      allergens. Various processing methods have been identified capable of reducing
      cow's milk protein allergenicity including thermal and non-thermal methods and
      their combinations. Heat treatment and enzymatic hydrolysis have been in
      production of hypoallergenic infant formulas. However, modulation of allergenic
      epitopes depends on the extent of heat treatment applied, which consequently may
      also reduce a nutritional value of these proteins. In addition, enzymatic
      hydrolysis may not target allergenic epitopes thus allergenicity may persist;
      however released peptides may have detrimental impact on taste and functional
      properties of final products. Modulation of allergenicity of milk proteins
      appears to require a concerted effort to minimize detrimental effects as clinical
      studies conducted on commercial hypoallergenic formulas demonstrated persistence
      of allergic symptoms. This article covers traditional and novel processing
      methods and their impact on reduction of cow's milk allergenicity in milk-based
      infant formulas.

PMID- 29658776
TI  - Toward Recovering Allele-specific Cancer Genome Graphs.
AB  - Integrated analysis of structural variants (SVs) and copy number alterations in
      aneuploid cancer genomes is key to understanding tumor genome complexity. A
      recently developed algorithm, Weaver, can estimate, for the first time, allele
      specific copy number of SVs and their interconnectivity in aneuploid cancer
      genomes. However, one major limitation is that not all SVs identified by Weaver
      are phased. In this article, we develop a general convex programming framework
      that predicts the interconnectivity of unphased SVs with possibly noisy allele
      specific copy number estimations as input. We demonstrated through applications
      to both simulated data and HeLa whole-genome sequencing data that our method is
      robust to the noise in the input copy numbers and can predict SV phasings with
      high specificity. We found that our method can make consistent predictions with
      Weaver even if a large proportion of the input variants are unphased. We also
      applied our method to The Cancer Genome Atlas (TCGA) ovarian cancer whole-genome
      sequencing samples to phase SVs left unphased by Weaver. Our work provides an
      important new algorithmic framework for recovering more complete allele-specific
      cancer genome graphs.

PMID- 29658777
TI  - Simple Comparative Analyses of Differentially Expressed Gene Lists May
      Overestimate Gene Overlap.
AB  - Comparing the overlap between sets of differentially expressed genes (DEGs)
      within or between transcriptome studies is regularly used to infer similarities
      between biological processes. Significant overlap between two sets of DEGs is
      usually determined by a simple test. The number of potentially overlapping genes
      is compared to the number of genes that actually occur in both lists, treating
      every gene as equal. However, gene expression is controlled by transcription
      factors that bind to a variable number of transcription factor binding sites,
      leading to variation among genes in general variability of their expression.
      Neglecting this variability could therefore lead to inflated estimates of
      significant overlap between DEG lists. With computer simulations, we demonstrate
      that such biases arise from variation in the control of gene expression.
      Significant overlap commonly arises between two lists of DEGs that are randomly
      generated, assuming that the control of gene expression is variable among genes
      but consistent between corresponding experiments. More overlap is observed when
      transcription factors are specific to their binding sites and when the number of
      genes is considerably higher than the number of different transcription factors.
      In contrast, overlap between two DEG lists is always lower than expected when the
      genetic architecture of expression is independent between the two experiments.
      Thus, the current methods for determining significant overlap between DEGs are
      potentially confounding biologically meaningful overlap with overlap that arises
      due to variability in control of expression among genes, and more sophisticated
      approaches are needed.

PMID- 29658778
TI  - ShRangeSim: Simulation of Single Nucleotide Polymorphism Clusters in Next
      Generation Sequencing Data.
AB  - Genomic variations are in the focus of research to uncover mechanisms of host
      pathogen interactions and diseases such as cancer. Nowadays, next-generation
      sequencing (NGS) data are analyzed through dedicated pipelines to detect them.
      Surrogate NGS data in conjunction with genomic variations help to evaluate
      pipelines and validate their outcomes, fostering selection of proper tools for a
      given scientific question. I describe how existing approaches for simulating NGS
      data in conjunction with genomic variations fail to model local enrichments of
      single nucleotide polymorphisms (SNPs), so called SNP clusters. Two distributions
      for count data are applied to publicly available collections of genomic
      variations. The results suggest modeling of SNP cluster sizes by overdispersion
      aware distributions.

PMID- 29658779
TI  - Fully Closed-Loop Multiple Model Probabilistic Predictive Controller Artificial
      Pancreas Performance in Adolescents and Adults in a Supervised Hotel Setting.
AB  - BACKGROUND: Initial Food and Drug Administration-approved artificial pancreas
      (AP) systems will be hybrid closed-loop systems that require prandial meal
      announcements and will not eliminate the burden of premeal insulin dosing.
      Multiple model probabilistic predictive control (MMPPC) is a fully closed-loop
      system that uses probabilistic estimation of meals to allow for automated meal
      detection. In this study, we describe the safety and performance of the MMPPC
      system with announced and unannounced meals in a supervised hotel setting.
      RESEARCH DESIGN AND METHODS: The Android phone-based AP system with remote
      monitoring was tested for 72 h in six adults and four adolescents across three
      clinical sites with daily exercise and meal challenges involving both three
      announced (manual bolus by patient) and six unannounced (no bolus by patient)
      meals. Safety criteria were predefined. Controller aggressiveness was adapted
      daily based on prior hypoglycemic events. RESULTS: Mean 24-h continuous glucose
      monitor (CGM) was 157.4 +/- 14.4 mg/dL, with 63.6 +/- 9.2% of readings between 70
      and 180 mg/dL, 2.9 +/- 2.3% of readings <70 mg/dL, and 9.0 +/- 3.9% of readings
      >250 mg/dL. Moderate hyperglycemia was relatively common with 24.6 +/- 6.2% of
      readings between 180 and 250 mg/dL, primarily within 3 h after a meal. Overnight
      mean CGM was 139.6 +/- 27.6 mg/dL, with 77.9 +/- 16.4% between 70 and 180 mg/dL,
      3.0 +/- 4.5% <70 mg/dL, 17.1 +/- 14.9% between 180 and 250 mg/dL, and 2.0 +/-
      4.5%> 250 mg/dL. Postprandial hyperglycemia was more common for unannounced meals
      compared with announced meals (4-h postmeal CGM 197.8 +/- 44.1 vs. 140.6 +/- 35.0
      mg/dL; P < 0.001). No participants met safety stopping criteria. CONCLUSIONS:
      MMPPC was safe in a supervised setting despite meal and exercise challenges.
      Further studies are needed in a less supervised environment.

PMID- 29658781
TI  - Evaluation of the radiation dose in the thyroid gland using different protective
      collars in panoramic imaging.
AB  - BACKGROUND: The value for the use of thyroid shield is one of the issues in
      radiation protection of patients in dental panoramic imaging. OBJECTIVES: The
      objective of this research is to investigate the attenuation characteristics of
      some models of thyroid shielding in dental panoramic examinations. METHODS: The
      effects of five different types of lead and lead-free (Pb-equivalent) shields on
      dose reduction of thyroid gland were investigated using implanted
      Thermoluminescence Dosemeters (TLDs) in head-neck parts of a Rando phantom.
      RESULTS: The results show that frontal lead and Pb-equivalent shields can reduce
      the thyroid dose around 50% and 19%, respectively. CONCLUSIONS: It can be
      concluded that the effective shielding area is an important parameter in thyroid
      gland dose reduction. Lead frontal collars with large effective shielding areas
      (>~300 cm2 but not necessarily very large) are appropriate for an optimized
      thyroid gland dose reduction particularly for the critical patients in dental
      panoramic imaging. Regardless of the shape and thickness, using the Pb-equivalent
      shields is not justifiable in dental panoramic imaging.

PMID- 29658780
TI  - Inter- and intra-observer variability of an anatomical landmark-based, manual
      segmentation method by MRI for the assessment of skeletal muscle fat content and
      area in subjects from the general population.
AB  - OBJECTIVES: Changes in skeletal muscle composition, such as fat content and mass,
      may exert unique metabolic and musculoskeletal risks; however, the
      reproducibility of their assessment is unknown. We determined the variability of
      the assessment of skeletal muscle fat content and area by MRI in a population
      based sample. METHODS: A random sample from a prospective, community-based cohort
      study (KORA-FF4) was included. Skeletal muscle fat content was quantified as
      proton-density fat fraction (PDFF) and area as cross-sectional area (CSA) in
      multi-echo Dixon sequences (TR 8.90 ms, six echo times, flip angle 4 degrees ) by
      a standardized, anatomical landmark-based, manual skeletal muscle segmentation at
      level L3 vertebra by two independent observers. Reproducibility was assessed by
      intraclass correlation coefficients (ICC), scatter and Bland-Altman plots.
      RESULTS: From 50 subjects included (mean age 56.1 +/- 8.8 years, 60.0% males,
      mean body mass index 28.3 +/- 5.2) 2'400 measurements were obtained.
      Interobserver agreement was excellent for all muscle compartments (PDFF: ICC0.99,
      CSA: ICC0.98) with only minor absolute and relative differences (-0.2 +/- 0.5%,
      31 +/- 44.7 mm2; -2.6 +/- 6.4% and 2.7 +/- 3.9%, respectively). Intra-observer
      reproducibility was similarly excellent (PDFF: ICC1.0, 0.0 +/- 0.4%, 0.4%; CSA:
      ICC1.0, 5.5 +/- 25.3 mm2, 0.5%, absolute and relative differences, respectively).
      All agreement was independent of age, gender, body mass index, body height and
      visceral adipose tissue (ICC0.96-1.0). Furthermore, PDFF reproducibility was
      independent of CSA (ICC0.93-0.99).  Conclusions:  Quantification of skeletal
      muscle fat content and area by MRI using an anatomical landmark-based, manual
      skeletal muscle segmentation is highly reproducible. Advances in knowledge: An
      anatomical landmark-based, manual skeletal muscle segmentation provides high
      reproducibility of skeletal muscle fat content and area and may therefore serve
      as a robust proxy for myosteatosis and sarcopenia in large cohort studies.

PMID- 29658782
TI  - Phylogenetic Copy-Number Factorization of Multiple Tumor Samples.
AB  - Cancer is an evolutionary process driven by somatic mutations. This process can
      be represented as a phylogenetic tree. Constructing such a phylogenetic tree from
      genome sequencing data is a challenging task due to the many types of mutations
      in cancer and the fact that nearly all cancer sequencing is of a bulk tumor,
      measuring a superposition of somatic mutations present in different cells. We
      study the problem of reconstructing tumor phylogenies from copy-number
      aberrations (CNAs) measured in bulk-sequencing data. We introduce the Copy-Number
      Tree Mixture Deconvolution (CNTMD) problem, which aims to find the phylogenetic
      tree with the fewest number of CNAs that explain the copy-number data from
      multiple samples of a tumor. We design an algorithm for solving the CNTMD problem
      and apply the algorithm to both simulated and real data. On simulated data, we
      find that our algorithm outperforms existing approaches that either perform
      deconvolution/factorization of mixed tumor samples or build phylogenetic trees
      assuming homogeneous tumor samples. On real data, we analyze multiple samples
      from a prostate cancer patient, identifying clones within these samples and a
      phylogenetic tree that relates these clones and their differing proportions
      across samples. This phylogenetic tree provides a higher resolution view of copy
      number evolution of this cancer than published analyses.

PMID- 29658784
TI  - Fast Metagenomic Binning via Hashing and Bayesian Clustering.
AB  - We introduce GATTACA, a framework for fast unsupervised binning of metagenomic
      contigs. Similar to recent approaches, GATTACA clusters contigs based on their
      coverage profiles across a large cohort of metagenomic samples; however, unlike
      previous methods that rely on read mapping, GATTACA quickly estimates these
      profiles from kmer counts stored in a compact index. This approach can result in
      over an order of magnitude speedup, while matching the accuracy of earlier
      methods on synthetic and real data benchmarks. It also provides a way to index
      metagenomic samples (e.g., from public repositories such as the Human Microbiome
      Project) offline once and reuse them across experiments; furthermore, the small
      size of the sample indices allows them to be easily transferred and stored.
      Leveraging the MinHash technique, GATTACA also provides an efficient way to
      identify publicly available metagenomic data that can be incorporated into the
      set of reference metagenomes to further improve binning accuracy. Thus, enabling
      easy indexing and reuse of publicly available metagenomic data sets, GATTACA
      makes accurate metagenomic analyses accessible to a much wider range of
      researchers.

PMID- 29658783
TI  - Fibrosarcoma arising in the paranasal sinus: a clinicopathological and
      radiological analysis.
AB  - OBJECTIVES: To analyze the clinicopathological features and the CT and MRI
      features of patients with paranasal sinus fibrosarcoma. METHODS: Seven patients
      with surgically and pathologically confirmed paranasal sinus fibrosarcoma were
      enrolled. Their CT and MRI data and imaging features were retrospectively
      analyzed in detail. RESULTS: The study participants were two males and five
      females (median age, 43 years; range, 22-73 years). CT or MRI showed a well
      defined (n = 5) or ill-defined (n = 2), irregular (n = 6) or oval (n = 1) mass,
      with heterogeneous (n = 7) density. The lesions were isointense (n = 4) or
      hypointense (n = 2) on T1 weighted images, and showed heterogeneous (n = 6) mild
      hypointensity on T2 weighted images. Expansive (n = 6) and osteolytic (n = 1)
      bone destruction were observed. The tumors showed marked heterogeneous delayed
      enhancement (n = 6) on contrast-enhanced MRI images. CONCLUSION: Paranasal sinus
      fibrosarcomas should be included in the differential diagnosis when a sinonasal
      neoplasm appears as a well- or ill-defined unilateral large irregular mass with
      characteristic mild hypointensity on T2 weighted MR images and shows expansive or
      osteolytic bone destruction and a marked heterogeneous delayed contrast
      enhancement pattern.

PMID- 29658785
TI  - Smartphone use and schema-based learning in dentomaxillofacial radiology
      practice: a case report from one College of Dentistry.
AB  - OBJECTIVES: This study investigates the students' satisfaction and awareness of
      competency towards smartphone use and schema-based learning in dental radiology
      practice. METHODS: Third year students undertaking a dental radiology practicum
      at a dental school were divided into two groups: one group received traditional
      clinical training, whereas the other group used smartphones in classes and
      received new training using schema assignments. At the end of the course,
      students' satisfaction with the training and self-awareness of their competency
      were surveyed, and their achievement was assessed. RESULTS: Although students'
      satisfaction with smartphone-based training was generally high, it was less than
      that of students trained by traditional instruction. However, most students that
      received smartphone-based training had higher self-scored competency before than
      after training. The smartphone group scored higher on true/false or multiple
      choice questions, whereas the traditional group scored higher on short-answer
      questions. CONCLUSIONS: Smartphone education with schema based assignment proved
      to be attractive in dental radiology, but students showed less satisfaction, and
      need to meet the requirements of evidence-based practice. Although the full use
      of smartphone education with schema is not recommended in dental education, we
      think that it could be try to use as a supplementary approach with traditional
      didactic method to facilitate student's exploration and self-study to cope with
      rapid change in educational environment.

PMID- 29658786
TI  - Imaging findings of mammary and systemic silicone deposition secondary to breast
      implants.
AB  - In patients with silicone breast implants, implant rupture can occur, which can
      be intra- or extracapsular. Following implant rupture, silicone can travel
      through the lymphatic system into regional and distant lymph nodes. The purpose
      of this pictorial essay is to present findings of silicone implant rupture with
      intramammary and systemic silicone deposition as seen on dual energy CT,
      ultrasound, mammogram, PET/CT and MRI. We include imaging findings of silicone
      deposition in the breast in cases of intra- and extracapsular rupture. We also
      present silicone deposition in mediastinal, axillary, and internal mammary lymph
      nodes, as well as in the liver and spleen. To our knowledge, deposition of
      silicone in the liver and spleen has not been previously demonstrated on cross
      sectional imaging. While all imaging modalities were able to detect silicone in
      the spleen, ultrasound appeared to be more sensitive than dual energy CT or MRI
      for detection of silicone deposition in the liver.

PMID- 29658787
TI  - Sodium Phenylbutyrate Inhibits Tumor Growth and the Epithelial-Mesenchymal
      Transition of Oral Squamous Cell Carcinoma In Vitro and In Vivo.
AB  - Sodium phenylbutyrate (SPB) as a salt of 4-phenylbutyric acid (4-PBA) has been
      reported to be an ammonia scavenger, histone deacetylase inhibitor, and an
      endoplasmic reticulum stress inhibitor in various diseases, including
      neurological diseases, inflammatory disorders, and carcinogenesis. Although
      phenylbutyrate showed effective antitumor properties in many cancers, its role in
      oral squamous cell carcinoma (OSCC) remains further characterized. Thus, the OSCC
      cell lines CAL27, HSC3, and SCC4 were treated with a series of doses of SPB for
      different times. The IC50 of three cell lines for SPB was determined to be 4.0,
      3.7, and 3.0 mM. The CCK-8 assay indicated that the treatment of SPB induced
      continuous inhibition of cell vitality of three cell lines. Apoptosis was
      assessed by Hoechst assay that showed that SPB could significantly promote cell
      apoptosis. Moreover, the apoptosis-related pathway was analyzed, and the results
      showed that the expression of antiapoptosis factor BCL-2 was downregulated by SPB
      but the cleavage of caspase-3 was increased. Meanwhile, it was found that SPB
      also impaired the migration and invasion of OSCC cells in vitro. Mechanistically,
      the transforming growth factor-beta (TGFB) related epithelial-mesenchymal
      transition (EMT) was inhibited by SPB with decreased mesenchymal marker N
      cadherin and increased epithelial marker E-cadherin. Furthermore, the antitumor
      effect of SPB in vivo was also demonstrated. The administration of SPB induced
      remarkably tumor regression with decreased tumor volume, and the TGFB level and
      EMT phenotype in vivo were also inhibited. These data demonstrated that the
      treatment of SPB could function as antitumor therapeutics for OSCC.

PMID- 29658788
TI  - Literature Search and Review.

PMID- 29658789
TI  - Effect of 2-Phenylethanol as Antifungal Agent and Common Antifungals
      (Amphotericin B, Fluconazole, and Itraconazole) on Candida Species Isolated from
      Chronic and Recurrent Cases of Candidal Vulvovaginitis.
AB  - The antifungal effects of 2-phenylethanol are clearly visible through its
      intervention in Candida morphogenesis. Chronic and recurrent vulvovaginitis,
      however, does not respond to this standard experimental therapy; therefore, the
      study presented in this article investigated the effect of common antifungal
      drugs (amphotericin B [AMB], fluconazole [FLU], and itraconazole [ITC]), in
      combination with 2-phenylethanol, on the Candida species isolated from cases of
      chronic and recurrent vulvovaginitis, thereby allowing the recommendation of a
      more appropriate treatment option. Forty isolates from patients with chronic and
      recurrent vaginal candidiasis were investigated in this experimental study. The
      specimens were examined by direct microscopy, culturing, and PCR to identify the
      species. The antifungal effects of 2-phenylethanol and conventional drugs, both
      alone and in combination, were determined in duplicate. Finally, the findings
      were analyzed. In this study, 40 strains of Candida species were identified,
      whose agents were Candida albicans (95%) and Candida africana (5%). After 48 h,
      the minimum inhibitory concentration (MIC) range of the 2-phenylethanol was 800
      3,200 MUg/mL. Also, in the final study on the MIC levels of common antifungal
      drugs, AMB (0.42 MUg/mL) had the lowest MIC, FLU (40.51 MUg/mL) had the highest
      MIC, and the combination of ITC and 2-phenylethanol had the lowest fractional
      inhibitory concentration index (FICI) of any of the combinations (FICI range,
      0.26-1.03). Combining FLU and ITC with 2-phenylethanol can effectively increase
      their antifungal effect.

PMID- 29658790
TI  - A High-Throughput Time-Resolved Fluorescence Energy Transfer Assay to Screen for
      Modulators of RGS7/Gbeta5/R7BP Complex.
AB  - G protein-coupled receptors (GPCRs) are excellent drug targets exploited by
      majority of the Food and Drug Administration-approved medications, but when
      modulated, are often accompanied by significant adverse effects. Targeting of
      other elements in GPCR pathways for improved safety and efficacy is thus an unmet
      need. The strength of GPCR signaling is tightly regulated by regulators of G
      protein signaling (RGS) proteins, making them attractive drug targets. We focused
      on a prominent RGS complex in the brain consisting of RGS7 and its binding
      partners Gbeta5 and R7BP. These complexes play critical roles in regulating
      multiple GPCRs and essential physiological processes, yet no small molecule
      modulators are currently available to modify its function. In this study, we
      report a novel high-throughput approach to screen for small molecule modulators
      of the intramolecular transitions in the RGS7/Gbeta5/R7BP complex known to be
      involved in its allosteric regulation. We developed a time-resolved fluorescence
      energy transfer-based in vitro assay that utilizes full-length recombinant
      proteins and shows consistency, excellent assay statistics, and high level of
      sensitivity. We demonstrated the potential of this approach by screening two
      compound libraries (LOPAC 1280 and MicroSource Spectrum). This study confirms the
      feasibility of the chosen strategy for identifying small molecule modulators of
      RGS7/Gbeta5/R7BP complex for impacting signaling downstream of the GPCRs.

PMID- 29658791
TI  - High-Throughput Gene Expression Profiles to Define Drug Similarity and Predict
      Compound Activity.
AB  - By adding biological information, beyond the chemical properties and desired
      effect of a compound, uncharted compound areas and connections can be explored.
      In this study, we add transcriptional information for 31K compounds of Janssen's
      primary screening deck, using the HT L1000 platform and assess (a) the
      transcriptional connection score for generating compound similarities, (b)
      machine learning algorithms for generating target activity predictions, and (c)
      the scaffold hopping potential of the resulting hits. We demonstrate that the
      transcriptional connection score is best computed from the significant genes only
      and should be interpreted within its confidence interval for which we provide the
      stats. These guidelines help to reduce noise, increase reproducibility, and
      enable the separation of specific and promiscuous compounds. The added value of
      machine learning is demonstrated for the NR3C1 and HSP90 targets. Support Vector
      Machine models yielded balanced accuracy values >=80% when the expression values
      from DDIT4 & SERPINE1 and TMEM97 & SPR were used to predict the NR3C1 and HSP90
      activity, respectively. Combining both models resulted in 22 new and confirmed
      HSP90-independent NR3C1 inhibitors, providing two scaffolds (i.e., pyrimidine and
      pyrazolo-pyrimidine), which could potentially be of interest in the treatment of
      depression (i.e., inhibiting the glucocorticoid receptor (i.e., NR3C1), while
      leaving its chaperone, HSP90, unaffected). As such, the initial hit rate
      increased by a factor 300, as less, but more specific chemistry could be
      screened, based on the upfront computed activity predictions.

PMID- 29658792
TI  - Scandium and terbium radionuclides for radiotheranostics: current state of
      development towards clinical application.
AB  - Currently, different radiometals are in use for imaging and therapy in nuclear
      medicine: 68Ga and 111In are examples of nuclides for positron emission
      tomography (PET) and single photon emission computed tomography (SPECT),
      respectively, while 177Lu and 225Ac are used for beta-- and alpha-radionuclide
      therapy. The application of diagnostic and therapeutic radionuclides of the same
      element (radioisotopes) would utilize chemically-identical radiopharmaceuticals
      for imaging and subsequent treatment, thereby enabling the radiotheranostic
      concept. There are two elements which are of particular interest in this regard:
      Scandium and Terbium. Scandium presents three radioisotopes for theranostic
      application. 43Sc (T1/2 = 3.9 h) and 44Sc (T1/2 = 4.0 h) can both be used for
      PET, while 47Sc (T1/2 = 3.35 d) is the therapeutic match-also suitable for SPECT.
      Currently, 44Sc is most advanced in terms of production, as well as with pre
      clinical investigations, and has already been employed in proof-of-concept
      studies in patients. Even though the production of 43Sc may be more challenging,
      it would be advantageous due to the absence of high-energetic gamma-ray emission.
      The development of 47Sc is still in its infancy, however, its therapeutic
      potential has been demonstrated preclinically. Terbium is unique in that it
      represents four medically-interesting radioisotopes. 155Tb (T1/2 = 5.32 d) and
      152Tb (T1/2 = 17.5 h) can be used for SPECT and PET, respectively. Both
      radioisotopes were produced and tested preclinically. 152Tb has been the first Tb
      isotope that was tested (as 152Tb-DOTATOC) in a patient. Both radionuclides may
      be of interest for dosimetry purposes prior to the application of radiolanthanide
      therapy. The decay properties of 161Tb (T1/2 = 6.89 d) are similar to 177Lu, but
      the coemission of Auger electrons make it attractive for a combined beta-/Auger
      electron therapy, which was shown to be effective in preclinical experiments.
      149Tb (T1/2 = 4.1 h) has been proposed for targeted alpha-therapy with the
      possibility of PET imaging. In terms of production, 161Tb and 155Tb are most
      promising to be made available at the large quantities suitable for future
      clinical translation. This review article is dedicated to the production routes,
      the methods of separating the radioisotopes from the target material, preclinical
      investigations and clinical proof-of-concept studies of Sc and Tb radionuclides.
      The availability, challenges of production and first (pre)clinical application,
      as well as the potential of these novel radionuclides for future application in
      nuclear medicine, are discussed.

PMID- 29658793
TI  - Growing BI-RADS category 3 lesions on follow-up breast ultrasound: malignancy
      rates and worrisome features.
AB  - OBJECTIVE:   To determine the frequency and malignancy rate among growing Breast
      Imaging Reporting and Data System (BI-RADS) category 3 lesions diagnosed on
      follow-up breast ultrasound and to evaluate the radiological and clinical
      features associated with malignancy.  Methods:  Of the 38,482 women who underwent
      breast ultrasound between January 2010 and December 2011, 11,582 (30.1%) patients
      had 12,514 BI-RADS category 3 lesions. Patients whose lesions showed >=20%
      enlargement on follow-up ultrasound were selected for this study. Radiological
      and clinical features including increase in the maximum diameter and
      anteroposterior dimension, morphological changes determined via ultrasound,
      palpability, multiplicity, new mass, baseline breast ultrasound indication and
      mammographic BI-RADS category were evaluated to determine their association with
      malignancy. Multivariate analyses were used to identify independent predictors of
      malignancy.  Results:  The frequency of growing BI-RADS category 3 lesions on
      follow-up ultrasound was 5.9% (738 of 12,514). Of 527 lesions examined in 459
      patients with a follow-up duration of at least 24 months or with available
      pathological results, 26 proved to be malignant (4.9%). Multivariate analyses
      further indicated that sonographic morphological changes (OR, 7.662, p < 0.001)
      and development of suspicious features on follow-up mammography (OR, 3.812, p =
      0.009) were associated with malignancy. Enlargement without associated suspicious
      mammography or sonographic morphological abnormalities had only 1.9 % (BI-RADS
      category 3) chance of malignancy.  Conclusion:  The malignancy rate for growing
      BI-RADS category 3 lesions is 4.9%. Sonographic morphological changes and
      suspicious mammographic features in these tumors are significantly associated
      with malignancy. Advances in knowledge: For lesions with an interval growth in
      the anteroposterior dimension of <=50% without morphological changes, together
      with a benign mammogram, follow-up rather than an immediate biopsy can be
      recommended to reduce false-positive biopsy results. The risk of malignancy in
      lesions with a size increment but with no morphologic change on sonography is
      only 1.9%, compatible with continued BI-RADS category 3 classification.

PMID- 29658794
TI  - Views of general practitioners toward physiotherapy management of osteoarthritis
      a qualitative study.
AB  - BACKGROUND: Osteoarthritis (OA) is a major cause of pain and physical disability,
      and general practitioners (GPs) are usually the first point of contact for
      patients. Physiotherapy has been shown as effective in the management of lower
      limb OA. The aim was to explore the beliefs of GPs on the physiotherapy
      management of lower-limb OA in primary care. METHODS: This is a qualitative study
      evaluating GP views about physiotherapy in Sheffield, South Yorkshire, UK.
      Participating GPs were recruited by systematic sampling, and invitation was given
      to GPs in 10 practices in the four localities in Sheffield. Semistructured
      interviews were completed and framework analysis was used to analyze the data.
      RESULTS: Eight GPs were interviewed and six themes emerged from analysis of the
      data: perspective on OA, management strategy, views on patients, views on
      physiotherapy, working collaboratively, and suggestions for service improvements.
      GPs had a positive impression and knowledge of physiotherapy, but lacked
      understanding of the processes involved in treatment and limited awareness of
      clinical guidelines regarding the management of OA. Improvements in communication
      and collaborative working were critical issues suggested by the participants.
      CONCLUSION: This study found that GPs who were interviewed had a limited
      understanding on the role of physiotherapists and of clinical guidelines.
      Interprofessional communication was not as good as it should have been. A
      reconfiguration of the Sheffield musculoskeletal pathway may help achieve more
      effective collaborative working and a better outcome for patients.

PMID- 29658796
TI  - Lichen sclerosus of the oral mucosa: clinical and histopathological findings.
      Review of the literature and a case report.
AB  - OBJECTIVES: Lichen sclerosus (LS) is a rare, chronic mucocutaneous disease that
      most frequently affects the female genital area. Oral manifestations are seldom
      detected; only 36 well-documented and histopathologically verified oral LS cases
      have been published. MATERIALS AND METHODS: Here we describe one patient affected
      by oral (LS) and review of the literature 1957-2017. RESULTS: Findings in our
      review suggest a female to male ratio of 1.64:1. It is most commonly diagnosed at
      the age of 10-29 years (46%). Oral LS can appear as symptomless, irregular
      shaped, porcelain-white and flat lesions situated asymmetrically. Lesion is
      commonly sole, well-demarcated area and its size varies from 2 mm (small macula)
      to 7 cm (large plaque). The most common sites in the oral cavity include the
      labial mucosa, lips and gingiva. The histopathological criteria include atrophy
      and sometimes hyperkeratosis of the epithelium, hydropic degeneration of basal
      cells, hyalinization of the lamina propria, lymphocyte infiltration beneath the
      zone of hyalinization and scantiness of elastin. Surgical excision is an
      effective treatment for small lesions; intralesional triamcinolone or
      corticosteroid injections are used for larger lesions. CONCLUSIONS: Oral LS may
      be under-recognized due to its asymptomatic nature and rarity.

PMID- 29658797
TI  - Physical activity during hospitalization: Activities and preferences of adults
      versus older adults.
AB  - OBJECTIVE: Inactivity during hospitalization leads to a functional decline and an
      increased risk of complications. To date, studies focused on older adults. This
      study aims to compare the physical activities performed by older adult and adult
      hospitalized patients. METHODS: Patients hospitalized for >3 days at a university
      hospital completed a questionnaire regarding their physical activities (% of days
      on which an activity was performed divided by the length of stay) and physical
      activity needs during hospitalization. Crude and adjusted comparisons of older
      adult (>60 years) and adult (<=60 years) patients were performed using parametric
      testing and regression analyses. RESULTS: Of 524 patients, 336 (64%) completed
      the questionnaire, including 166 (49%) older adult patients. On average, the
      patients were physically active on 35% or less of the days during their
      hospitalization. Linear regression analysis showed no significant associations
      between being an older adult and performing physical activities after adjusting
      for gender, length of stay, surgical intervention, and meeting physical activity
      recommendations prior to hospitalization. Most patients were well informed
      regarding physical activity during hospitalization; however, the older adult
      patients reported a need for information regarding physical activities after
      hospitalization more frequently (odds ratios, 2.47) after adjusting for
      educational level, gender, and physical therapy during hospitalization.
      CONCLUSIONS: Both older adult and adult patients are physically inactive during
      hospitalization, and older adult patients express a greater need for additional
      information regarding physical activity after hospitalization than adult
      patients. Therefore, personalized strategies that inform and motivate patients to
      resume physical activities during hospitalization are needed regardless of age.

PMID- 29658795
TI  - An update and systematic review on drug therapies for the treatment of refractory
      chronic cough.
AB  - INTRODUCTION: Chronic Cough (CC) is common and often associated with significant
      comorbidity and decreased quality of life. In up to 50% of cases, the cough is
      refractory despite extensive investigation and treatment trials. It is likely
      that the key abnormality in refractory CC is dysfunctional, hypersensitive
      sensory nerves, similar to conditions such as laryngeal hypersensitivity and
      neuropathic pain. Areas covered: The aim of this systematic review is to assess
      drug therapies for refractory CC. The authors review the current management of CC
      and provide discussion of the similarities between neuropathic pain and
      refractory CC. They review repurposed and new pharmacological treatments. Several
      meta-analyses were performed to compare the efficacy of treatments where
      possible. Expert opinion: Repurposed pain medications such as gabapentin and
      pregabalin reduce the frequency of cough and improve quality of life. Along with
      speech pathology, they are important and alternate treatments for refractory CC.
      However, more treatments are needed and the P2X3 ion channel receptor antagonists
      show the most promise. With a better understanding of neuronal activation and
      sensitisation and their signal processing in the brain, improved animal models of
      cough, and the use of validated cough measurement tools, more effective
      treatments will develop.

PMID- 29658798
TI  - Mock ECHO: A Simulation-Based Medical Education Method.
AB  - PROBLEM: This study was designed to develop a deeper understanding of the
      learning and social processes that take place during the simulation-based medical
      education for practicing providers as part of the Project ECHO(r) model, known as
      Mock ECHO training. The ECHO model is utilized to expand access to care of common
      and complex diseases by supporting the education of primary care providers with
      an interprofessional team of specialists via videoconferencing networks.
      INTERVENTION: Mock ECHO trainings are conducted through a train the trainer model
      targeted at leaders replicating the ECHO model at their organizations. Trainers
      conduct simulated teleECHO clinics while participants gain skills to improve
      communication and self-efficacy. CONTEXT: Three focus groups, conducted between
      May 2015 and January 2016 with a total of 26 participants, were deductively
      analyzed to identify common themes related to simulation-based medical education
      and interdisciplinary education. Principal themes generated from the analysis
      included (a) the role of empathy in community development, (b) the value of
      training tools as guides for learning, (c) Mock ECHO design components to
      optimize learning, (d) the role of interdisciplinary education to build community
      and improve care delivery, (e) improving care integration through collaboration,
      and (f) development of soft skills to facilitate learning. OUTCOME: Mock ECHO
      trainings offer clinicians the freedom to learn in a noncritical environment
      while emphasizing real-time multidirectional feedback and encouraging knowledge
      and skill transfer. LESSONS LEARNED: The success of the ECHO model depends on
      training interprofessional healthcare providers in behaviors needed to lead a
      teleECHO clinic and to collaborate in the educational process. While building a
      community of practice, Mock ECHO provides a safe opportunity for a diverse group
      of clinician experts to practice learned skills and receive feedback from
      coparticipants and facilitators.

PMID- 29658799
TI  - The validity and reliability of the ADL-Glittre test for children.
AB  - OBJECTIVE: The ADL-Glittre was created to assess more comprehensively the
      essential activities of daily living in adults with chronic obstructive pulmonary
      disease. The aim of this study was to validate the ADL-Glittre test adapted for
      children (TGlittre-P) and verify its reliability. METHODS: This is a cross
      sectional study with 87 healthy children aged 6 to 14 years (mean 10.36 +/- 2.32
      years). Biometric and spirometry data were collected from all participants. On
      the same day, part of the sample (36 children included in the validation process)
      performed two 6MWT and two TGlittre-P (30-minute interval between them). The
      other part of the sample just performed two TGlittre-P for the reliability
      process. Pearson and Spearman correlation tests were used to verify the
      correlation between the time spent on the TGlittre-P and the distance walked in
      the 6MWT. The intraclass correlation coefficient (ICC) was also used to assess
      the reproducibility of the TGlittre-P. RESULTS: The TGlittre-P showed a moderate
      negative correlation with the 6MWT (r = -0.490; p = 0.002; 95%CI -0.712 to 
      0.233). However, the behavior of the physiological variables that were monitored
      during the tests was similar and showed to be reproducible (ICC = 0.843; p =
      0.000; 95%CI 0.695 to 0.911). CONCLUSION: The TGlittre-P proved to be a valid and
      reliable assessment of the functional capacity of healthy children aged 6 to 14
      years.

PMID- 29658800
TI  - Nail involvement in patients with moderate-to-severe alopecia areata treated with
      oral tofacitinib.
AB  - BACKGROUND: A few anecdotal case reports demonstrated that tofacitinib improved
      nail changes associated with AA. OBJECTIVE: To investigate nail changes in
      patients with AA treated with tofacitinib and evaluate the relationship between
      nail and hair responses to tofacitinib. METHODS: This is a retrospective study of
      33 adult patients with moderate-to-severe AA treated with oral tofacitinib
      monotherapy for at least 4 months. RESULTS: Fifteen patients had nail involvement
      and demonstrated more severe hair loss than those without nail involvement (p =
      .040). However, there was no significant difference in hair regrowth between two
      groups. Of 15 patients with nail involvement, 11 (73.3%) showed improvement
      regardless of type of nail change; the first improvement was observed at a median
      of 5 months (range, 1-11) after administration. Nail improvement was associated
      with neither initial severity of hair loss nor hair response to tofacitinib. Nail
      improvement tended to occur later than hair regrowth. CONCLUSIONS: Oral
      tofacitinib monotherapy improves nail involvement associated with AA. Nail
      involvement is not a poor prognosis factor in hair regrowth with tofacitinib
      treatment and there is no evident relationship between nail and hair responses.

PMID- 29658801
TI  - The effects of tandem skiing on posture and heart rate in children with profound
      intellectual and multiple disabilities.
AB  - PURPOSE: The objective of study was to determine the effect of tandem ski (TS)
      activity on postural control and cardiac activity in children with profound
      intellectual and multiple disabilities (PIMDs). METHOD: Twenty children with PIMD
      and 20 age-matched controls (typically developed (TD) children) participated.
      Body segment movements were measured with inertial sensors (Physilog(r)) placed
      on the head, C7, trunk (including ECG) and pelvis with a seat reference. Each
      participant was measured during a 12-turn slalom pattern. RESULTS: In each group,
      significant differences were observed between the head vs. trunk and head vs.
      pelvis angular speeds (p<0.001). In both groups, heart rate differed
      significantly during rest (PIMD 99 bpm, TD 97 bpm), exercise (PIMD 140 bpm, TD
      139 bpm; rest vs. exercise p<0.001) and recovery (PIMD 101 bpm, TD 107 bpm;
      exercise vs. recovery p<0.001). CONCLUSIONS: In children with PIMD, TS elicits
      active postural control associated with cardiac activities similar to that of the
      controls.

PMID- 29658802
TI  - A Qualitative Analysis of Narrative Preclerkship Assessment Data to Evaluate
      Teamwork Skills.
AB  - : Construct: Students entering the health professions require competency in
      teamwork. BACKGROUND: Although many teamwork curricula and assessments exist,
      studies have not demonstrated robust longitudinal assessment of preclerkship
      students' teamwork skills and attitudes. Assessment portfolios may serve to fill
      this gap, but it is unknown how narrative comments within portfolios describe
      student teamwork behaviors. APPROACH: We performed a qualitative analysis of
      narrative data in 15 assessment portfolios. Student portfolios were randomly
      selected from 3 groups stratified by quantitative ratings of teamwork performance
      gathered from small-group and clinical preceptor assessment forms. Narrative data
      included peer and faculty feedback from these same forms. Data were coded for
      teamwork-related behaviors using a constant comparative approach combined with an
      identification of the valence of the coded statements as either "positive
      observation" or "suggestion for improvement." RESULTS: Eight codes related to
      teamwork emerged: attitude and demeanor, information facilitation, leadership,
      preparation and dependability, professionalism, team orientation, values team
      member contributions, and nonspecific teamwork comments. The frequency of codes
      and valence varied across the 3 performance groups, with students in the low
      performing group receiving more suggestions for improvement across all teamwork
      codes. CONCLUSIONS: Narrative data from assessment portfolios included specific
      descriptions of teamwork behavior, with important contributions provided by both
      faculty and peers. A variety of teamwork domains were represented. Such feedback
      as collected in an assessment portfolio can be used for longitudinal assessment
      of preclerkship student teamwork skills and attitudes.

PMID- 29658803
TI  - Evening types demonstrate reduced SSRI treatment efficacy.
AB  - Selective serotonin reuptake inhibitors (SSRIs) have a profound effect on the
      circadian system's response to environmental light, which may impact treatment
      outcomes for patients depending on their habitual light exposure patterns. Here,
      we investigated the relationship between time-of-day preference, depressive
      symptoms and self-reported antidepressant treatment response. Evening types
      reported having taken a higher number of antidepressant medications in the
      previous 5 years and lower SSRI efficacy than morning types. While undergoing
      SSRI treatment, evening types also reported more depressive symptoms and
      suicidality. It is concluded that time-of-day preference may prove informative in
      predicting SSRI treatment responses.

PMID- 29658804
TI  - Comparison of Effects of Endurance and Strength Training Programs in Patients
      with COPD.
AB  - : Comparisons between endurance and strength training in chronic obstructive
      pulmonary disease (COPD) patients have produced equivocal findings when examining
      physical function and health-related quality of life (HRQL). One reason for these
      differences may be due to individual patient responses to the different training
      modalities. PURPOSE: To compare changes in physical function and HRQL in a group
      of COPD patients completing both an endurance and a strength training program.
      METHODS: Eleven mildly diseased patients completed a three month endurance
      training program and, approximately 5 years later, completed a three month
      strength training program. Changes in 6 minute walk distance (6 MW), time to rise
      from a chair five times (CRT), and the total score and subscores from the SF-36
      and Chronic Respiratory Disease Questionnaire (CRQ) were examined. RESULTS: The
      forced expiratory volume as a percent of predicted remained relatively constant
      over the 5 years (61.1 +/- 5.9 vs. 60.0 +/- 10.3). Endurance and strength
      training increased 6 MW by 48.2 +/- 11.2 (p = 0.008) and 39.8 +/- 9.8 (p = 0.001)
      meters, respectively. Endurance and strength training decreased CRT by 4.8 +/-
      0.7 (p = 0.001) and 1.3 +/- 1.2 (p = 0.056) seconds, respectively. Endurance
      training resulted in greater improvements in HRQL as compared to strength
      training. CONCLUSION: These results show that walk distance improves as a result
      of participating in either an endurance or a strength training program. However,
      an endurance training program leads to greater improvements in both general and
      disease specific measures of HRQL.

PMID- 29658805
TI  - Subclinical hypothyroidism is not a risk factor for polycystic ovary syndrome in
      obese women of reproductive age.
AB  - Obese women are at high risk for polycystic ovary syndrome (PCOS). Subclinical
      hypothyroidism (SCH) has been associated with weight gain, insulin resistance and
      impaired fertility, which are also factors involved in PCOS. However, there is
      limited information regarding the influence of SCH on the presence of PCOS. In
      order to determine whether SCH increases the prevalence of PCOS, we performed a
      cross-sectional study in a cohort of reproductive-aged obese women. All subjects
      underwent anthropometric evaluation, laboratory tests and ultrasound examination.
      Diagnosis of PCOS was based on the Rotterdam criteria. A total of 534 obese women
      were included and 108 (20.2%) of them were diagnosed with SCH. Patients with SCH
      showed similar insulin resistance, comparable androgen levels, and higher
      triglycerides levels (1.7 vs. 1.5 mmol/L, p = .002) compared to those with normal
      thyroid status. The frequency of PCOS did not differ between the two groups
      (56.1% for normal thyroid function vs. 60.2% for subclinical hypothyroidism, p =
      .514). In logistic regression analysis, SCH was not an independent risk factor
      for PCOS after adjusting for confounding factors (OR = 0.984, 95% CI 0.581
      1.667). For the first time, our results suggest that SCH does not increase the
      risk of PCOS in obese women of reproductive age.

PMID- 29658806
TI  - Nanobodies and Cancer: Current Status and New Perspectives.
AB  - Reducing the dimension of antigen-binding proteins to an only immunoglobulin
      domain has been one of the objectives of antibody manufacturing. Heavy chain
      antibodies were encountered while attempting to separate the blood serum proteins
      of dromedaries. Later the term "nanobodies" (Nbs) was introduced. The
      advantageous features of Nbs comprise little immunogenicity, stability at
      low/high pH, capacity to target antigens that are less antigenic, and, lastly,
      easy capability to be used for therapy against tumor cells. Presently, Nbs have
      been used for several medical and biotechnological purposes. Numerous Nb-derived
      formats have been positively proved useful for targeting drug delivery, and
      bioimaging.

PMID- 29658807
TI  - Effect of bright light therapy on delayed sleep/wake cycle and reaction time of
      athletes participating in the Rio 2016 Olympic Games.
AB  - This study investigated the effect of using an artificial bright light on the
      entrainment of the sleep/wake cycle as well as the reaction times of athletes
      before the Rio 2016 Olympic Games. A total of 22 athletes from the Brazilian
      Olympic Swimming Team were evaluated, with the aim of preparing them to compete
      at a time when they would normally be about to go to bed for the night. During
      the 8-day acclimatization period, their sleep/wake cycles were assessed by
      actigraphy, with all the athletes being treated with artificial light therapy for
      between 30 and 45 min (starting at day 3). In addition, other recommendations to
      improve sleep hygiene were made to the athletes. In order to assess reaction
      times, the Psychomotor Vigilance Test was performed before (day 1) and after (day
      8) the bright light therapy. As a result of the intervention, the athletes slept
      later on the third (p = 0.01), seventh (p = 0.01) and eighth (p = 0.01) days
      after starting bright light therapy. Regarding reaction times, when tested in the
      morning the athletes showed improved average (p = 0.01) and minimum reaction time
      (p = 0.03) when comparing day 8 to day 1. When tested in the evening, they showed
      improved average (p = 0.04), minimum (p = 0.03) and maximum reaction time (p =
      0.02) when comparing day 8 to day 1. Light therapy treatment delayed the
      sleep/wake cycles and improved reaction times of members of the swimming team.
      The use of bright light therapy was shown to be effective in modulating the
      sleep/wake cycles of athletes who had to perform in competitions that took place
      late at night.

PMID- 29658808
TI  - Defining antimicrobial stewardship competencies for undergraduate health
      professional education in the United Kingdom: A study protocol.
AB  - Multi-drug resistant infections have been identified as one of the greatest
      threats to human health. Healthcare professionals are involved in an array of
      patient care activities for which an understanding of antimicrobial stewardship
      is important. Although antimicrobial prescribing and stewardship competencies
      have been developed for healthcare professionals who adopt the role of a
      prescriber, competencies do not exist for other medicine-related stewardship
      activities. Undergraduate education provides an ideal opportunity to prepare
      healthcare professionals for these roles and activities. This report presents a
      protocol for a study designed to provide national consensus on antimicrobial
      stewardship competencies appropriate for undergraduate healthcare professional
      education. A modified Delphi process will be used in which a panel of Experts,
      comprising members from across the United Kingdom, with expertise in prescribing
      and medicines management with regard to the education and practice of healthcare
      professionals, and antimicrobial prescribing and stewardship, will be invited to
      take part in two survey rounds. The competencies developed will be applicable to
      all undergraduate healthcare professional education programmes. They will help to
      standardise curricula content and enhance the impact of antimicrobial stewardship
      education.

PMID- 29658809
TI  - The Gaussian Graphical Model in Cross-Sectional and Time-Series Data.
AB  - We discuss the Gaussian graphical model (GGM; an undirected network of partial
      correlation coefficients) and detail its utility as an exploratory data analysis
      tool. The GGM shows which variables predict one-another, allows for sparse
      modeling of covariance structures, and may highlight potential causal
      relationships between observed variables. We describe the utility in three kinds
      of psychological data sets: data sets in which consecutive cases are assumed
      independent (e.g., cross-sectional data), temporally ordered data sets (e.g., n =
      1 time series), and a mixture of the 2 (e.g., n > 1 time series). In time-series
      analysis, the GGM can be used to model the residual structure of a vector
      autoregression analysis (VAR), also termed graphical VAR. Two network models can
      then be obtained: a temporal network and a contemporaneous network. When
      analyzing data from multiple subjects, a GGM can also be formed on the covariance
      structure of stationary means-the between-subjects network. We discuss the
      interpretation of these models and propose estimation methods to obtain these
      networks, which we implement in the R packages graphicalVAR and mlVAR. The
      methods are showcased in two empirical examples, and simulation studies on these
      methods are included in the supplementary materials.

PMID- 29658810
TI  - Early Changes in eDiary COPD Symptoms Predict Clinically Relevant Treatment
      Response at 12 Weeks: Analysis from the CRYSTAL Study.
AB  - Early detection of treatment response is important in the long-term treatment and
      management of patients with chronic obstructive pulmonary disease (COPD). This
      analysis evaluated whether early improvement in symptoms, recorded in the first 7
      or 14 days via an electronic diary (eDiary) compared with baseline, can predict
      clinically meaningful treatment responders at 12 weeks. CRYSTAL was a 12-week,
      randomized, open-label study that demonstrated the increased effectiveness of
      indacaterol/glycopyrronium (IND/GLY) or glycopyrronium (GLY), after a direct
      switch from on-going baseline therapies, in patients with symptomatic COPD and
      moderate airflow obstruction. The co-primary endpoints were trough forced
      expiratory volume in 1 second (FEV1) and transition dyspnea index (TDI) at Week
      12. Patients' symptom status was recorded daily in an eDiary. Of 4,389 patients
      randomized, 3,936 and 3,855 reported symptoms on Days 7 and 14, respectively.
      Patients who reported an early decrease in symptoms on Day 7 or 14 were more
      likely to achieve the minimal clinically important difference of >=100 mL in
      trough FEV1 or >= 1 point in TDI at Week 12. Using stepwise multivariate
      regression models we identified as best predictors of FEV1 responders the
      decrease in wheeze on Day 7, and nighttime symptoms and wheeze on Day 14; best
      predictors of TDI responders were decrease in nighttime symptoms and wheeze on
      Day 7, and nighttime symptoms, sputum and wheeze on Day 14. Early symptom
      improvement at Day 7 or 14, especially wheeze and nighttime symptoms, may
      identify patients with clinically important improvement in lung function and
      dyspnea at Week 12.

PMID- 29658811
TI  - Parathyroid Autotransplantation During thyroid Surgery. Where we are? A
      Systematic Review on Indications and Results.
AB  - INTRODUCTION: Hypoparathyroidism still represents an important concern in thyroid
      surgery. Careful dissection with identification and preservation of parathyroid
      glands in situ remains the best way to maintain gland vitality and avoid post
      operative failure. Nevertheless, parathyroid glands are still inadvertently
      removed in up to 11% of cases. Parathyroid autotransplantation may represent the
      only way to restore parathyroid gland functionality in case of inadvertent
      removal or devascularization during thyroid surgery. Despite this, there is still
      no agreement on the effectiveness of this procedure. The present systematic
      review is focused on the mainly debated matters regarding the procedure,
      indications, technique and results. METHODS: This review has been carried out
      according to PRISMA statement and checklist. The research item was:
      (((parathyroid autotransplantation[Title]) OR parathyroid reimplantation[Title])
      NOT hyperparathyroidism[Title]) AND english[Language]. RESULTS: A total of 31
      studies have been found according to limitations already described, reporting
      from 4 to 890 procedures, with a total amount of 4088 PA. Among these studies,
      there are only 7 prospective case-series evaluations, 2 prospective randomized
      trials, while the other 22 studies are retrospective evaluations. The main
      concerns are: when and how to perform autotransplantation; in which anatomical
      site; which result to be expected, and how to manage and control the graft.
      Conslusions: Parathyroid autotransplantatin is an important tool to avoid or
      minimize the risk for hypoparathyroidism following thyroid surgery in selected
      cases. Parathormone assay can help the surgeon to determine when reimplantation
      is indicated or not. Further studies could theoretically give definitive results.

PMID- 29658812
TI  - Late chronotype and high social jetlag are associated with burnout in evening
      shift workers: Assessment using the Chinese-version MCTQshift.
AB  - Chronotypes are associated with shift work tolerance and sleep in shift workers,
      and sleep mediates the impact of shift work on mental health. However, the role
      of chronotype in the association between shift work and mental health has not
      been clarified. In this study, we aimed to examine the association between
      chronotype and burnout in shift workers, using the validated Munich ChronoType
      Questionnaire for shift workers (MCTQshift). A total of 288 shift workers with
      irregular shift frequencies were recruited and completed the Chinese-version
      MCTQshift and the Morningness-Eveningness Questionnaire (MEQ). Chronotypes were
      assessed by the calculation of corrected mid-sleep time (MSFSC) from mid-sleep
      time on free days (MSF) based on their exact shift schedules. Another 26 evening
      shift nurses were monitored with actigraphy for at least two consecutive evening
      shifts and the following two free days. Burnout was evaluated using the
      Copenhagen Burnout Inventory. We found that MSFESC, MSFE and mid-sleep time on
      workdays (MSWE) had normal distributions and correlated significantly with MEQ
      scores (r = - 0.47, -0.45 and -0.47, respectively; all p < 0.001). MSW was more
      closely correlated with actigraphy-derived mid-sleep time on the free day before
      workdays than that on workdays (r = 0.61 and 0.48, respectively, p < 0.05). Sleep
      duration was significantly longer on workdays among evening-shift workers who
      slept late on workdays than those who slept early (beta = 0.59, p < 0.001). After
      demographic and work characteristics were adjusted for in linear regression
      models, late chronotype and high social jetlag were associated with burnout
      scores in evening-shift workers. In conclusion, the Chinese-version MCTQshift is
      a valid tool for chronotype assessment. Interventions to improve sleep in shift
      workers should be tailored to chronotype due to variations in sleep behavior.
      Late chronotype may be an inherent feature of mental health problems, because the
      association with burnout was significant in both day workers in previous studies
      and shift workers.

PMID- 29658813
TI  - Kinematic upper extremity performance in people with near or fully recovered
      sensorimotor function after stroke.
AB  - BACKGROUND: Clinical scales for upper extremity motor function may not capture
      improvement among higher functioning people with stroke. OBJECTIVE: To describe
      upper extremity kinematics in people with stroke who score within the upper 10%
      of the Fugl-Meyer Assessment (FMA-UE) and explore the ceiling effects of the FMA
      UE. DESIGN: A cross-sectional study design was used. PARTICIPANTS: People with
      stroke were included from the Stroke Arm Longitudinal Study at University of
      Gothenburg together with 30 healthy controls. The first analysis included
      participants who achieved FMA-UE score > 60 within the first year of stroke
      (assessed at 3 days, 2 weeks, 4 weeks, 3 months, or 12 months post stroke). The
      second analysis included participants with submaximal FMA-UE (60-65 points, n =
      24) or maximal FMA-UE score (66 points, n = 21) at 3 months post stroke.
      MEASUREMENTS: The kinematic analysis of a standardized drinking task included
      movement time, velocity and strategy, joint angles of the elbow, and shoulder and
      trunk displacement. RESULTS: The high FMA-UE stroke group showed deficits in
      seven of eight kinematic variables. The submaximal FMA-UE stroke group was
      slower, had lower tangential and angular peak velocity, and used more trunk
      displacement than the controls. In addition, the maximal FMA-UE stroke group
      showed larger trunk displacement and arm abduction during drinking and lower peak
      angular velocity of the elbow. CONCLUSIONS: Participants with near or fully
      recovered sensorimotor function after stroke still show deficits in movement
      kinematics; however, the FMA-UE may not be able to detect these impairments.

PMID- 29658814
TI  - Combined Spring and Deltoid Ligament Repair in Adult-Acquired Flatfoot.
AB  - BACKGROUND: Adult-acquired flatfoot deformity (AAFD) is usually due to a
      combination of mechanical failure of the osteoligamentous complex that maintains
      the medial longitudinal arch of the foot and attenuation or complete tear of the
      posterior tibial tendon. Magnetic resonance imaging studies in patients with
      flatfoot deformities have reported the posterior tibial tendon to be pathologic
      in up to 100% of patients, the spring ligament in up to 87%, and the deltoid
      ligament in 33%. Many studies in the literature describe reconstruction of the
      spring ligament or the deltoid ligament associated with AAFD, but there is no
      study in which both (spring and deltoid) ligaments are reconstructed at the same
      time. We describe a novel technique to reconstruct the deltoid ligament and the
      spring ligament at the same time. METHODS: We described the technique and
      evaluated 10 consecutive patients with AAFD and insufficient ankle and midfoot
      ligaments. RESULTS: We found no postoperative complications, stiffness, or loss
      of correction. CONCLUSION: We present a novel technique to reconstruct the failed
      deltoid and spring ligament during flatfoot correction. It is unique in that it
      uses internal brace augmentation with FiberTape(r) to help and protect the soft
      tissue healing. LEVEL OF EVIDENCE: Level IV, retrospective case series.

PMID- 29658815
TI  - Oxidative stress, NOx/l-arginine ratio and glutathione/glutathione S-transferase
      ratio as predictors of 'sterile inflammation' in patients with alcoholic
      cirrhosis and hepatorenal syndrome type II.
AB  - Continuous intake of alcohol leads to liver cirrhosis because of imbalance of
      oxidative stress/antioxidative defense and chronic 'sterile inflammation'.
      Hepatorenal syndrome (HRS) is the most severe complication of liver cirrhosis.
      The aim of our study was to assess: (1) the oxidative stress/antioxidative
      defense markers such as malondialdehyde (MDA), oxidative glutathione (GSH) and
      glutathione S-transferase (GST), (2) inflammation [C-reactive protein (CRP)], and
      (3) nitrate/nitrite levels (NOx) and its substrate L-arginine level. The study
      enrolled three groups: a group with cirrhosis and HRS (48 patients), a group with
      cirrhosis without HRS (32 patients), and a control group (40 healthy blood
      donors). All the patients with cirrhosis and HRS had type II HRS. MDA
      concentration was significantly higher in the groups with cirrhosis with and
      without HRS. Significant positive correlation was documented between the MDA
      level and de Ritis coefficient (AST/ALT), a marker of liver damage severity;
      between MDA and inflammation (CRP); between MDA and NOx concentration in the
      groups with cirrhosis with and without HRS. The correlation between MDA and
      creatinine level was significant in the group with HRS. The levels of GSH and GST
      were significantly lower in the groups with cirrhosis with and without HRS. The
      results of the study revealed that an increase in MDA and NOx concentration,
      along with decreased values of antioxidative defense and L-arginine, may indicate
      that liver damage can have an influence on progression to renal failure.

PMID- 29658816
TI  - A mixed treatment comparison of toxicity of gemcitabine combined with different
      targeted drugs in the treatment of advanced or metastatic pancreatic cancer.
AB  - The mixed treatment comparison study was performed in order to compare the
      toxicities of Gemcitabine and different targeted drug combinations in the
      treatment of advanced/metastatic pancreatic cancer (PC). Searches were performed
      from the inception of PubMed and Cochrane Library databases to February 2017.
      This study included randomized controlled trials (RCTs) of Gemcitabine and
      different targeted drug combinations in the treatment of advanced/metastatic PC.
      Odds ratio (OR) values were calculated by direct and indirect comparisons, and
      the surface under the cumulative ranking curves (SUCRA) were drawn. A total of
      six RCTs were finally incorporated into the study. These studies included six
      therapy regimens: Gemcitabine + Axitinib, Gemcitabine + Trametinib, Gemcitabine +
      Sorafenib, Gemcitabine + Bevacizumab, Gemcitabine + Erlotinib and Gemcitabine +
      Tipifarnib. The results showed that Gemcitabine + Axitinib combinations showed
      lower incidence rates of rashes (all grades) in comparison to Gemcitabine +
      Trametinib and Gemcitabine + Erlotinib combinations. Compared with Gemcitabine+
      Trametinib combinations, Gemcitabine + Axitinib combinations showed lower
      incidence rates of diarrhea (grade >= 3). Moreover, the cluster analyses results
      revealed that Gemcitabine + Axitinib combinations and Gemcitabine + Sorafenib
      combinations showed lower incidence rates of hematotoxicity, while Gemcitabine +
      Axitinib combinations showed lower incidence rates of non-hematotoxicity.
      Collectively, the data provided strong evidence of Gemcitabine + Axitinib
      combinations showing lower incidence rates of non-hematotoxicity, and Gemcitabine
      + Axitinib and Gemcitabine + Sorafenib combinations may have lower incidence
      rates of hematotoxicity in the treatment of advanced/metastatic PC.

PMID- 29658817
TI  - Racial and Ethnic Differences in Advance Care Planning: Results of a Statewide
      Population-Based Survey.
AB  - BACKGROUND: Few studies have focused on racial and ethnic differences in advance
      care planning other than advance directives among population-based samples of
      adults across the lifespan. METHODS: Using data from a statewide random-digit
      dial telephone survey of adults 18 years or older (n = 1851), we investigated
      racial and ethnic differences in (1) designation of a healthcare agent (HCA); and
      (2) communication of goals, values, and preferences for end-of-life care with
      healthcare providers, a HCA, or other family members and friends. RESULTS: Less
      than half (44%, 95% confidence interval [CI] = 41.3%-47.0%) of all participants
      had named a HCA. In multivariable analyses, participants who identified as
      Hispanic (adjusted odds ratio [aOR] = 0.4, 95% CI = 0.2-0.7) or non-Hispanic
      other (aOR = 0.6, 95% CI = 0.4-0.9) were less likely than non-Hispanic whites to
      have named a HCA. Only 14.5% (95% CI = 12.6%-16.5%) of all participants had ever
      had a conversation with a healthcare provider about their end-of-life care
      wishes, with no differences by race/ethnicity. Over half (53.9%, 95% CI = 51.0%
      56.8%) of all participants reported having had conversations with someone other
      than a healthcare provider about their end-of-life wishes. In multivariable
      analyses, non-Hispanic whites were more likely than Hispanics (aOR = 0.5, 95% CI
      = 0.3-0.7), black/African Americans (aOR = 0.5, 95% CI = 0.3-0.9), and non
      Hispanic others (aOR = 0.7, 95% CI = 0.5-1.0) to report having had such
      conversations. CONCLUSIONS: Racial and ethnic minorities may be disadvantaged in
      the quality of care they receive if they have a serious illness and are unable to
      make decisions for themselves because most have not talked to anyone about their
      goals, values, or preferences for care.

PMID- 29658819
TI  - Child and Family Factors Associated With Child Maltreatment in Vietnam.
AB  - This study aims to explore possible risk factors for child maltreatment in
      Vietnam by investigating the association of child and family factors with
      different types of child maltreatment (i.e., sexual abuse, physical abuse,
      emotional abuse, witnessing parental conflict, and neglect) and the occurrence of
      multiple types of child maltreatment. Cross-sectional data of 1,851 secondary and
      high school students aged 12 to 17 years (47.3% boys) in four provinces of
      Northern Vietnam were obtained using self-report questionnaires. Results
      indicated that the likelihood of emotional abuse, witnessing parental conflict,
      and experiencing multiple types of child maltreatment during lifetime increased
      with age. Boys had a higher risk than girls on lifetime sexual abuse, and past
      year and lifetime physical abuse. Living in a single parent family was the risk
      factor related to most types of child maltreatment including lifetime sexual
      abuse, neglect, and multiple types of child maltreatment, and both past year and
      lifetime witnessing parental conflict. Interestingly, low socioeconomic status
      (SES) and parental unemployment were associated with a decreased risk on
      experiencing emotional abuse in the past year and during lifetime, respectively.
      "Tiger parenting," a parenting style observed frequently in East Asian parents,
      may be more common in families with high SES and might explain this finding. This
      study highlights the importance of prioritizing single parent families in
      parenting programs and implementing child maltreatment interventions early
      because of the risk on child maltreatment increased with age. More research on
      emotional abuse and "Tiger parenting" in Vietnam could clarify the association of
      emotional abuse with high SES and parental employment. Finally, the underlying
      mechanisms of the risk factors in Vietnam should be studied more to inform
      interventions.

PMID- 29658818
TI  - A long non-coding SINEUP RNA boosts semi-stable production of fully human
      monoclonal antibodies in HEK293E cells.
AB  - Use of monoclonal antibodies is emerging as a highly promising and fast
      developing scenario for innovative treatment of viral, autoimmune and tumour
      diseases. The search for diagnostic and therapeutic antibodies currently depends
      on in vitro screening approaches, such as phage and yeast display technologies.
      Antibody production still represents a critical step for preclinical and clinical
      evaluations. Accordingly, improving production of monoclonal antibodies
      represents an opportunity, to facilitate downstream target validations. SINEUP
      RNAs are long non-coding transcripts, possessing the ability to enhance
      translation of selected mRNAs. We applied SINEUP technology to semi-stable
      production of monoclonal antibodies in HEK293E cells, which allows for episomal
      propagation of the expression vectors encoding the heavy and light chains of
      IgGs. Co-expression of SINEUP RNA with mRNAs encoding heavy and light chains of
      IgG4s was able to increase the production of different anti-CLDN1 antibodies up
      to three-fold. Improved production of monoclonal antibodies was achieved both in
      transiently transfected HEK293E cells and in cellular clones with stable
      expression of the SINEUP. Compared to antibody preparations obtained under
      standard conditions, the anti-CLDN1 IgG4s produced in the presence of the SINEUP
      transcript showed unaltered post-translational modifications, and retained the
      ability to recognize their target. We thus propose SINEUP technology as a
      valuable tool to enhance semi-stable antibody production in human cell lines.

PMID- 29658820
TI  - Umbilical Microbiome and Laparoscopic Surgery: A Descriptive Clinical Study.
AB  - BACKGROUND: The human skin microbiome consists of colonizing and pathogen germs.
      The umbilical dimple is a humid environment prone to bacterial colonization and
      growth. In the laparoscopic era, the umbilicus has become the most common site of
      entrance into the peritoneum. The aim of this study was to describe the
      characteristics of umbilical microflora before antiseptic skin preparation.
      METHODS: Descriptive single-center study. A series of patients who underwent
      laparoscopic/open and elective/urgent abdominal surgery over a 2-month period
      were included. Patients were admitted the same day or the day before surgery.
      Before antiseptic skin preparation, microbiological samples were taken from the
      umbilicus, left upper abdominal quadrant, and nostril. A delayed referral time
      (>30 minutes) of the skin swabs to the microbiology laboratory was an exclusion
      criterion. RESULTS: Overall, 70 patients were included. The median age was 64
      years (range 16-89) and a laparoscopic approach was used in 82.8% of cases. The
      most commonly performed operation was laparoscopic fundoplication for
      gastroesophageal reflux (25.8%). In the umbilicus, the most frequent colonizing
      bacteria were coagulase-negative Staphylococcus species and Corynebacterium.
      Opportunistic pathogens were found in 10 umbilical swabs compared with 8 in the
      left upper quadrant (14.2% versus 11.4%, p = .800). Overall, 50% of patients with
      umbilical opportunistic pathogens had a medium/high bacterial load compared with
      62.5% in the left upper quadrant (p = .958). No postoperative surgical site
      infection was recorded in the study sample. CONCLUSIONS: Both the umbilicus and
      the left upper quadrant appear to be safe entry sites in laparoscopic surgery.
      Meticulous hygiene of these anatomical areas is strongly recommended before
      surgery regardless of the type of antiseptic solution and the short-term
      antibiotic prophylaxis. In-hospital preoperative showers may be unnecessary for
      well-educated patients.

PMID- 29658821
TI  - Top Ten Tips for Palliative Care Clinicians Caring for Cancer Patients Receiving
      Immunotherapies.
AB  - Patients with cancer face an ever-changing landscape of tumor-directed therapies
      available to improve quality of life and potentially increase survival. The most
      recent advances, immunotherapeutics, offer a novel way to target cancer cells by
      engaging the body's own immune system. Using an expert panel of oncologists,
      palliative medicine physicians, and dual-trained specialists, we discuss current
      immunotherapies and their clinical uses, potential side effects and management
      strategies, and the implications of these newer treatments on goals of care
      conversations and care coordination. We aim to further engage palliative care
      specialists in the active care of cancer patients receiving immunotherapeutics
      and use a "Top 10" tips format to concisely present practical learning points to
      busy clinicians.

PMID- 29658822
TI  - [Cluster-randomized, controlled evaluation of stress management training for high
      school students].
AB  - : Cluster-randomized, controlled evaluation of stress management training for
      high school students Abstract. OBJECTIVE: One fifth of German adolescents show
      elevated levels of mental health problems. The development of mental health
      problems is often closely related to experiences of stress. Hence, fostering
      competences in coping with stress offers an approach for counteracting the
      development of psychological problems. The aim of the present study is to test a
      stress management training of 3 x 90 minutes in a German high school, 11th grade.
      METHOD: A cluster-randomized, controlled design was used. The primary outcome was
      stress. Secondary outcome criteria were knowledge about stress, coping behaviour,
      emotional and behavioural problems as well as health-related quality of life.
      Students from twenty-one courses from four schools participated in the study.
      RESULTS: The sample comprised 286 students (58.25 % girls; mean age 16.58 +/-
      0.65). Changes in stress levels from pre- to post-evaluation did not differ
      significantly between intervention and control group. With regard to secondary
      criteria, apart from a significant increase in knowledge no further effects were
      observed. An exploratory moderation analysis hints at a positive association
      between baseline levels of stress and effectiveness of the training. CONCLUSIONS:
      The results question whether the universal application of a brief cognitive
      behavioural intervention is appropriate to prevent stress in this population.
      Future research should, inter alia, investigate the potential of indicated
      prevention regarding stress.

PMID- 29658823
TI  - Totally Laparoscopic Mini-ALPPS Using a Novel Approach of Laparoscopic-Assisted
      Transmesenteric Portal Vein Embolization.
AB  - BACKGROUND: The initial mortality rates of associating liver partition and portal
      vein occlusion for staged hepatectomy (ALPPS) were high. However, recent data
      from the International Registry show a continuous reduction of early mortality
      and major morbidity due to risk adjustment in patient selection and less invasive
      techniques in stage-1 surgery. During the first ALPPS International Consensus in
      2015, we introduced a paradigm inversion of ALPPS, the so-called "Mini-ALPPS."
      METHODS: We combined a partial liver partition with a novel technique of
      laparoscopic-assisted percutaneous cannulation of the inferior mesenteric vein
      for intraoperative transmesenteric portal vein embolization. We report here for
      the first time, a case of a successful totally laparoscopic Mini-ALPPS, and
      describe in detail the technical aspects of this new approach. RESULTS: A 61-year
      old man with a 6 cm hepatocellular carcinoma compromising the right glissonian
      pedicle in a fibrotic liver was treated by an extended right hepatectomy using
      the laparoscopic Mini-ALPPS approach. The patient had an uneventful first stage
      and was discharged 3 days after. A CT scan performed on postoperative day 8
      showed sufficient future liver remnant volume after a 59% hypertrophy. An
      extended right hepatectomy was uneventfully completed and the patient was
      discharged 5 days after surgery. The histopathological analysis indicated
      advanced F4 liver fibrosis and negative tumor margins. CONCLUSIONS: This
      technical innovation allows avoiding a laparotomy to access the mesenteric venous
      territory and the risks of liver remnant injuries during percutaneous
      transhepatic approach. This new alternative may result of great utility not only
      in ALPPS but also for many different circumstances and scenarios.

PMID- 29658824
TI  - Video-Assisted Thoracoscopic Surgery Lobectomy Performed Satisfaction and
      Complications of Patients During Hands-On Training Courses.
AB  - AIM: It was aimed to concern about the satisfaction and procedural complications
      of patients during the thoracoscopy exist of hands-on training in this present
      study. PATIENTS AND METHODS: The patients with non-small-cell carcinoma underwent
      video-assisted thoracoscopic surgery (VATS) lobectomy during hands-on training
      courses at thoracoscopic center in our hospital and collected from January 2009
      and December 2014. The rates of satisfaction and complications of patients were
      compared from hands-on training group and control group. Potential risk factors
      associated with post-VATS complications of patients and thoracoscopist-related
      variables were analyzed. There were 54 patients join in six meetings with hands
      on thoracoscopy training in our center. RESULTS: There was no significant
      difference between patients for hands-on training group (n = 54) and control
      group (n = 54), including sex, age, BMI, smoking, PpoFEV1 and comorbidities. The
      satisfaction rate and the incidence of complication were similar between the two
      groups. CONCLUSION: Univariate analyses showed that elder age, heart disease,
      chronic obstructive pulmonary disease, long operative time, and first-time
      mentorship were significantly associated with post-VATS complications of patients
      in hands-on training group. We should pay more attention to the characteristics
      of patent and the experience of mentor before VATS hands-on training courses.

PMID- 29658825
TI  - Alternative kinship structures, resilience and social support among immigrant
      trans Latinas in the USA.
AB  - Latinas comprise the largest racial/ethnic group of trans women (male-to-female
      transgender people) in New York City, where HIV seroprevalence among trans
      Latinas has been found to be as high as 49%. Despite this population's high risk
      of HIV, little is known about resilience among trans Latinas that may provide
      protective health factors. Six focus groups and one in-depth interview were
      conducted with 34 low-income trans/gender-variant people of colour who attended
      transgender support groups at harm reduction programmes in New York City. This
      paper reports on data from 13 participants who identified as immigrant trans
      Latinas. Focus groups were coded and analysed using thematic qualitative methods.
      The majority of immigrants were undocumented but reported having robust social
      support. Unique characteristics of immigrant trans Latinas included alternative
      kinship structures and sources of income. Social creativity was used to develop
      achievable ways in which to improve their health outcomes. Resilience was evident
      in informal kinship dynamics, formal support groups, gender-transition,
      educational access and skills training and substance use reduction. Individual
      level resilience increased as a result of strong community-level resilience.

PMID- 29658826
TI  - College Students' Experiences with, and Willingness to Use, Different Types of
      Telemental Health Resources: Do Gender, Depression/Anxiety, or Stress Levels
      Matter?
AB  - OBJECTIVE: Telemental health (TMH) resources are plentiful; however, we know
      little about college students' opinions about such resources. We aimed to examine
      students' previous use of and willingness to use several types of TMH resources.
      PARTICIPANTS: Students (N = 662) from two U.S. Midwestern colleges participated.
      METHODS: Using an online survey in spring 2017, we measured students' depression,
      anxiety, stress, and suicidal thoughts, preferences for care options during
      distress, and use and interest in anonymous chats with trained nonprofessionals,
      online therapy, and self-help resources. RESULTS: Overall, 10.1-13.8% had
      experience with these TMH resources; however, 24.6-40.1% expressed willingness to
      try them. At-risk students, especially those higher in depression/anxiety scores,
      showed greater use of and willingness to use some applications. CONCLUSIONS:
      Counseling centers might consider endorsing TMH resources as potential pathways
      to care. TMH resources might help broaden reach with minimal cost, reduce mental
      health help-seeking barriers, and provide support to at-risk populations.

PMID- 29658827
TI  - Finite Element Method-Based Kinematics and Closed-Loop Control of Soft, Continuum
      Manipulators.
AB  - This article presents a modeling methodology and experimental validation for soft
      manipulators to obtain forward kinematic model (FKM) and inverse kinematic model
      (IKM) under quasi-static conditions (in the literature, these manipulators are
      usually classified as continuum robots. However, their main characteristic of
      interest in this article is that they create motion by deformation, as opposed to
      the classical use of articulations). It offers a way to obtain the kinematic
      characteristics of this type of soft robots that is suitable for offline path
      planning and position control. The modeling methodology presented relies on
      continuum mechanics, which does not provide analytic solutions in the general
      case. Our approach proposes a real-time numerical integration strategy based on
      finite element method with a numerical optimization based on Lagrange multipliers
      to obtain FKM and IKM. To reduce the dimension of the problem, at each step, a
      projection of the model to the constraint space (gathering actuators, sensors,
      and end-effector) is performed to obtain the smallest number possible of
      mathematical equations to be solved. This methodology is applied to obtain the
      kinematics of two different manipulators with complex structural geometry. An
      experimental comparison is also performed in one of the robots, between two other
      geometric approaches and the approach that is showcased in this article. A closed
      loop controller based on a state estimator is proposed. The controller is
      experimentally validated and its robustness is evaluated using Lypunov stability
      method.

PMID- 29658828
TI  - Sustainable Telemedicine: Designing and Building Infrastructure to Support a
      Comprehensive Telemedicine Practice.
AB  - BACKGROUND: Telemedicine services in medical institutions are often developed in
      isolation of one another and not as part of a comprehensive telemedicine program.
      The Center for Connected Care is the administrative home for a broad range of
      telehealth services at Mayo Clinic. This article speaks of real-time video
      services, referenced as telemedicine throughout. INTRODUCTION: This article
      discusses how a large healthcare system designed and built the infrastructure to
      support a comprehensive telemedicine practice. MATERIALS AND METHODS: Based on
      analysis of existing services, Mayo Clinic developed a multifaceted operational
      plan that addressed high-priority areas and outlined clear roles and
      responsibilities of the Center for Connected Care and that of the clinical
      departments. The plan set priorities and a direction that would lead to long-term
      success. The plan articulated the governing and operational infrastructure
      necessary to support telemedicine by defining the role of the Center for
      Connected Care as the owner of core administrative operations and the role of the
      clinical departments as the owners of clinical telemedicine services. Additional
      opportunities were identified to develop product selection processes,
      implementation services, and staffing models that would be applied to ensure
      successful telemedicine deployment. RESULTS: The telemedicine team within the
      Center for Connected Care completed 45 business cases resulting in 54
      implementations. The standardization of core products along with key operational
      offerings around implementation services, and the establishment of a 24/7 support
      model resulted in improved provider satisfaction and fewer reported technical
      issues. CONCLUSION: The foundation for long-term scalability and growth was
      developed by centralizing operations of telemedicine services, implementing
      sustainable processes, employing dedicated qualified personnel, and deploying
      robust products.

PMID- 29658829
TI  - Playground love: sex work, pleasure, and self-affirmation in the urban nightlife
      of Indonesian waria.
AB  - Indonesian transgender women, locally and internationally recognised as waria,
      share some lifestyle patterns that have emerged under conditions of limited
      social acceptance. These patterns include involvement in sex work. The high
      number of waria who are sex workers is usually explained in economic terms.
      However, their presence in certain locations around the city known for waria sex
      work is not only for work, and quite often not even for sex. Waria street
      nightlife fosters waria agency, which emerges from self-affirmation through
      pleasurable bodily practices involving intimate (sexual partners) and both
      proximate (other waria and men nearby) and distant others (structuring ideals).
      Drawing on fieldwork conducted between 2010 and 2015 in Java and West Papua, this
      paper describes the political and economic organisation of sex work among waria,
      then highlights the social and sensorial qualities of waria street nightlife.

PMID- 29658830
TI  - 'You'll always stay right': understanding vaginal products and the motivations
      for use among adolescent and young women in rural KZN.
AB  - The use of vaginal products may increase the risk of HIV infection by affecting
      the vaginal biome. Understanding what vaginal products young women are using, and
      why, is key to assessing the complexity of sexual health and risk. This study
      reports on findings from research with adolescent and young women in rural
      KwaZulu-Natal about the vaginal products they use and motivations for using them.
      The study identified over 26 products that young women used to enhance their
      sexual experience and found some young women spent time preparing and sourcing
      vaginal products in order to pleasure and retain partners. Opinions differed
      about vaginal product use. While some women perceived that vaginal products could
      provide a means of out-performing other women, retaining a partner and providing
      sexual autonomy, there was a stigma attached to using them. Study findings
      highlight the social value of using vaginal products, especially in settings
      where partner retention is linked to economic survival. Expanding our
      understanding of what products are used and the reasons young women use them
      warrants continued investigation.

PMID- 29658831
TI  - Short-burst interval treadmill training walking capacity and performance in
      cerebral palsy: a pilot study.
AB  - PURPOSE: To examine the effect of short-burst interval locomotor treadmill
      training (SBLTT) on walking capacity and performance in cerebral palsy (CP).
      METHODS: Twelve children with spastic diplegic CP (average 8.6 years) across
      Gross Motor Function Classification System levels II (8) and III (4) were
      randomized to 20 SBLTT sessions over 4 or 10 weeks. SBLTT consisted of
      alternating 30 seconds of slow and fast walking for 30 minutes/session. Outcomes
      included the 10 m walk test, one-minute walk test (1MWT), and timed-up-and go
      (TUG) (capacity) and StepWatch (performance) collected at baseline, post, and 6
      weeks post. RESULTS: Fast speed (+.11, p = .04; +.11 m/s, p = .006), 1MWT (+11.2;
      +11.7 m, p = .006) and TUG (-1.7; -1.9 seconds, p = .006) improved post SBLTT and
      6 weeks, respectively. Walking performance increased: average strides/day (+948;
      +1712, p < .001) and percent time in high strides rates (+0.4, p = 0.07; +0.2, p
      = .008). CONCLUSIONS: Pilot study suggests SBLTT may improve short-term walking
      capacity and performance.

PMID- 29658832
TI  - THE ASSOCIATIONS BETWEEN HYPOVITAMINOSIS D, HIGHER PTH LEVELS WITH BONE MINERAL
      DENSITIES, AND RISK OF THE 10-YEAR PROBABILITY OF MAJOR OSTEOPOROTIC FRACTURES IN
      CHINESE PATIENTS WITH T2DM.
AB  - OBJECTIVE: In the current study, we investigated the vitamin D status, and its
      relationships with parathyroid hormone (PTH) levels, bone mineral density (BMD),
      and the 10-year probability of fractures in Chinese patients with type 2 diabetes
      mellitus (T2DM). METHODS: This was a cross-sectional study of 785 patients. BMDs
      at the lumbar spine (L2-4), femoral neck (FN), and total hip (TH) were measured
      by dual-energy X-ray absorptiometry (DXA). Serum levels of 25-hydroxyvitamin D
      (25(OH)D) and intact PTH were also quantified. The 10-year probability of
      fracture risk (major osteoporotic fracture [MOF] and hip fracture [HF]) was
      assessed using the fracture risk assessment tool (FRAX). RESULTS: The prevalence
      of vitamin D deficiency was 82.3%, and the mean 25(OH)D level was 36.9 +/- 15.2
      nmol/L. The adequate group had higher BMDs at the FN and TH and lower MOF risk
      than the inadequate groups. Lower 25(OH)D was associated with higher PTH ( r = 
      0.126, P<.001). PTH was negatively correlated with BMDs at 3 sites and positively
      correlated with MOF and HF, but this relationship disappeared in the adequate
      subgroup. Multivariate stepwise regression analysis revealed that PTH was the
      determinant of MOF (standard beta = 0.073, P = .010) and HF (standard beta =
      0.094, P = .004). CONCLUSION: Our results identified a significantly high rate of
      vitamin D deficiency among Chinese patients with T2DM. PTH is an important risk
      factor responsible for the higher 10-year probability of osteoporotic fractures
      in diabetic patients, especially in those with lower vitamin D levels.
      ABBREVIATIONS: AKP = alkaline phosphatase; ALB = serum albumin; BMD = bone
      mineral density; BMI = body mass index; Ca = calcium; CKD = chronic kidney
      disease; Cr = creatinine; FN = femoral neck; FRAX = fracture risk assessment
      tool; HbA1c = glycated hemoglobin A1c; HF = hip fracture; L2-4 = lumbar spine;
      MOF = major osteoporotic fracture; 25(OH)D = 25-hydroxyvitamin D; P = phosphorus;
      PTH = parathyroid hormone; T2DM = type 2 diabetes mellitus; TH = total hip; UA =
      uric acid.

PMID- 29658833
TI  - GONADOPENIA AND AGING IN MEN.
AB  - OBJECTIVE: The decrease in testosterone levels that occurs with aging has become
      an important clinical issue both due to the growth of the geriatric population
      and patient interest in testosterone therapy. The decision to assess for
      testosterone deficiency and the ability to determine whether the benefits exceed
      the risks require a comprehensive evaluation of the aging patient. This article
      is part of a series of papers focused on the endocrinology of aging. This review
      addresses common issues needed for clinical decision making, including how to
      interpret test results, differential diagnosis, potential impact of testosterone
      treatment on insulin resistance and cardiovascular disease, and options for
      therapy. METHODS: Papers reviewed were identified through literature searches
      conducted on PubMed. RESULTS: Assessment of testosterone levels in the geriatric
      male requires an understanding of the limitations of the assay that is used, the
      symptoms associated with low testosterone, the impact of comorbid conditions on
      levels, and risks of therapy. Successful treatment requires setting realistic
      expectations of the benefits of replacement therapy. CONCLUSION: While the
      prevalence of low testosterone concentrations is increased with aging, the common
      comorbidities such as obesity and diabetes may contribute to changes in
      testosterone levels. Clinical trial evidence shows modest benefit for treatment
      of low testosterone in the presence of symptoms. Assessment of the geriatric male
      should include evaluation of their testosterone level in the context of their
      functional status and comorbidities. ABBREVIATIONS: CDC = Centers for Disease
      Control and Prevention; CI = confidence interval; CVD = cardiovascular disease;
      DXA = dual-energy X-ray absorptiometry; EMAS = European Male Aging Study; FDA =
      U.S. Food and Drug Administration; FHS = Framingham Heart Study; HDL = high
      density lipoprotein; HOMA-IR = homeostasis model assessment of insulin
      resistance; LH = luteinizing hormone; OR = odds ratio; PSA = prostate-specific
      antigen; SHBG = sex hormone-binding globulin; T2DM = type 2 diabetes mellitus;
      vBMD = volumetric bone mineral density.

PMID- 29658834
TI  - ALTERATIONS IN THYROID HORMONE LEVELS FOLLOWING GROWTH HORMONE REPLACEMENT EXERT
      COMPLEX BIOLOGICAL EFFECTS.
AB  - OBJECTIVE: Alterations in the thyroid axis are frequently observed following
      growth hormone (GH) replacement, but uncertainty exists regarding their clinical
      significance. We aimed to compare fluctuations in circulating thyroid hormone
      levels, induced by GH, to changes in sensitive biological markers of thyroid
      hormone action. METHODS: This was a prospective observational clinical study.
      Twenty hypopituitary men were studied before and after GH replacement. Serum
      thyroid-stimulating hormone (TSH), thyroid hormones, and insulin-like growth
      factor 1 were measured. Changes in thyroid hormone concentrations were compared
      to alterations in resting metabolic rate and cardiac time intervals. Health
      related quality of life (QOL) was assessed by disease-sensitive and generic
      questionnaires. RESULTS: Following GH replacement, free thyroxine concentration
      declined and free triiodothyronine level increased. Resting energy expenditure
      increased, particularly in subjects with profound hypopituitarism, including TSH
      deficiency (16.73 +/- 1.75 kcal/kg/min vs. 17.96 +/- 2.26 kcal/kg/min; P = .01).
      Alterations in the thyroid axis were more pronounced in subjects with a
      low/normal baseline respiratory quotient (RQ) who experienced a paradoxical rise
      in RQ (0.81 vs. 0.86; P = .01). Subjects with a high baseline RQ experienced a
      slight but nonsignificant fall in RQ without alteration in thyroid axis. The
      isovolumetric contraction time was shortened during the study; however, this did
      not reach statistical significance. Improvements in QOL were observed despite
      alterations in thyroid axis. CONCLUSION: Changes in the thyroid axis following GH
      replacement are associated with complex tissue-specific effects. These
      fluctuations may induce a hypothyroid phenotype in some tissues while appearing
      to improve the biological action of thyroid hormone in other organs.
      ABBREVIATIONS: AGHDA = Assessment of Growth Hormone Deficiency in Adulthood;
      CHOox = carbohydrate oxidation; ET = ejection time; fT3 = free triiodothyronine;
      fT4 = free thyroxine; GH = growth hormone; GHD = growth hormone deficiency; HB-RQ
      = high baseline respiratory quotient; HPT = hypothalamic-pituitary-thyroid; ICT =
      isovolumetric contraction time; IGF-1 = insulin-like growth factor 1; IRT =
      isovolumetric relaxation time; LB-RQ = low baseline respiratory quotient; LV =
      left ventricular; NHP = Nottingham Health Profile; QOL = quality of life; REE =
      resting energy expenditure; RQ = respiratory quotient; rT3 = reverse
      triiodothyronine; SF-36 = Short Form 36; TSH = thyroid-stimulating hormone; T3 =
      triiodothyronine; T4 = thyroxine; TT3 = total triiodothyronine; TT4 = total
      thyroxine.

PMID- 29658835
TI  - SONOGRAPHIC FEATURES OF MULTIFOCAL PAPILLARY THYROID CARCINOMAS.
AB  - OBJECTIVE: It is uncertain whether papillary thyroid carcinomas (PTCs) of the
      same subtype display similar sonographic features. This retrospective analysis of
      pre-operative sonographic and pathologic findings aimed to assess whether PTCs of
      the same subtype share sonographic features. METHODS: Before undergoing thyroid
      surgery, 137 patients underwent ultrasound (US) examination. A single radiologist
      used a picture archiving and communication system and pathologic reports to
      investigate all sonographic features of the largest and second largest PTCs.
      Additionally, the radiologist evaluated the similarity of sonographic features
      between primary (largest), secondary (second largest), and daughter (secondary
      with same subtype as the primary) PTCs. RESULTS: Of the 137 PTC patients, 48
      (35.0%) had multiple PTCs; however, 5 had no US images of the secondary PTC. Of
      the 43 secondary PTCs with US images, 9 (20.9%) secondary PTCs were of a
      different subtype than the primary PTC and revealed sonographic features that
      differed from those of the primary PTC. Of the 48 patients with multiple PTCs,
      the subtype was the same in the primary and secondary PTCs in 34 (70.8%)
      patients. Of the 34 daughter PTCs, 32 (94.1%) had sonographic features similar to
      those of the primary PTC, whereas 2 (5.9%) showed different sonographic features
      than the primary PTC. There was no significant difference between primary and
      daughter PTCs in the size, location, sonographic features, or Korean Thyroid
      Imaging Reporting and Data System category ( P>.05). CONCLUSION: Daughter PTCs
      show similar sonographic features as the primary PTC. ABBREVIATIONS: K-TIRADS =
      Korean Thyroid Imaging Reporting and Data System; PTC = papillary thyroid
      carcinoma; US = ultrasound.

PMID- 29658836
TI  - Lawrence A. Frohman, MD, An "Outstanding Leader in Endocrinology" (1935-2018).

PMID- 29658837
TI  - Immigration as a crisis tendency for HIV vulnerability among racialised women
      living with HIV in Ontario, Canada: an anti-oppressive lens.
AB  - South Asian immigrant women in Canada face unique structural barriers that
      influence their HIV vulnerability. Using an intersectional and anti-oppressive
      lens, we explored the role of immigration in bringing about changes in gender
      roles and the structure of gender relations and their effect on HIV risk among
      immigrant women as they experienced crisis tendencies in the face of hegemonic
      masculinity. Informed by Connell's theory of gender, the study entailed in-depth
      interviews with 12 self-identified South Asian immigrant women living in the
      Greater Toronto Area, in Ontario, Canada. A thematic analysis yielded four
      themes: power relations, emotional relations, gendered division of labour and
      social norms. Our findings revealed interdependencies between immigration and
      each of structural, individual and normative factors (the themes) as they pertain
      to crisis tendencies when patriarchy is disrupted. Given the rapid increase in
      global immigration, the connections between transnationalism and hegemony, and
      the established link between immigration and HIV, future research should extend
      this work to other immigrant communities.

PMID- 29658838
TI  - Effectiveness of translational manipulation under interscalene block for the
      treatment of adhesive capsulitis of the shoulder: A nonrandomized clinical trial.
AB  - STUDY DESIGN: Nonrandomized controlled trial. OBJECTIVE: To determine whether
      translational manipulation under anesthesia/local block (TMUA) adds to the
      benefit of mobilization and range of motion exercise for improving pain and
      functional status among patients with adhesive capsulitis of the shoulder (AC).
      BACKGROUND: TMUA has been shown to improve pain and dysfunction in patients with
      AC. This intervention has not been directly compared to physical therapy
      treatment without TMUA in a prospective trial. METHODS: Sixteen consecutive
      patients with a primary diagnosis of AC were divided into two groups. Patients in
      the first (TMUA) group received a session of translational manipulation under
      interscalene block, followed by six sessions of manipulation and exercise.
      Patients in the comparison group received seven sessions of manipulation and
      exercise. Outcome measures taken at baseline and 3, 6, 12 months and 4 years
      included Shoulder Pain and Disability Index (SPADI) scores. Four-year outcomes
      included percent of normal ratings, medication use, and activity limitations.
      RESULTS: Both groups showed improved SPADI scores across all follow-up times
      compared to baseline. The TMUA group showed a greater improvement in SPADI scores
      than the comparison group at 3 weeks, with no significant differences in SPADI
      scores at other time points. However, at 4 years, significantly more subjects in
      the comparison group (5 of 8) had activity limitations versus subjects in the
      TMUA group (1 of 8). No subject experienced a complication from either
      intervention protocol. CONCLUSION: Physical therapy consisting of manual therapy
      and exercise provides benefit for patients with AC. Translational manipulation
      under local block may be a useful adjunct to manual therapy and exercise for
      patients with AC.

PMID- 29658839
TI  - Comparison of Emergency Cholecystectomy with Delayed Cholecystectomy After
      Percutaneous Transhepatic Gallbladder Drainage in Patients with Moderate Acute
      Cholecystitis.
AB  - INTRODUCTION: Patients with moderate (grade II) acute cholecystitis patients, as
      defined by the 2013 Tokyo Guidelines, were retrospectively compared with respect
      to emergency cholecystectomy (EC) and delayed cholecystectomy (DC) after
      percutaneous transhepatic gallbladder drainage (PTGBD) to determine the better
      treatment strategy. METHODS: Forty-nine of 103 patients with PTGBD and 47 of 54
      patients with EC were assessed for eligibility from January 2013 to January 2017.
      Patients with the following conditions were included: (i) moderate (grade II)
      acute cholecystitis diagnosed by the 2013 Tokyo Guidelines; (ii) no common bile
      duct stones; (iii) no atrophic cholecystitis; (iv) no decompensated liver
      cirrhosis and massive ascites; (v) no diffuse peritonitis; (vi) surgeons are
      professors or associate professors; and (vii) PTGBD is not the only procedure for
      the patient defined by clinicians. The preoperative characteristics and
      postoperative outcomes were analyzed. PTGBD was performed by experienced
      interventional radiologists and cholecystectomy was performed by professors or
      associate professors. RESULTS: Patients in the EC and PTGBD + DC groups had
      similar demographic, clinical, preoperative laboratory, and imaging
      characteristics. Both PTGBD and EC resolved the cholecystitis quickly. Compared
      to the PTGBD + DC group, EC patients had more intraoperative bleeding (101 +/-
      125 mL versus 33 +/- 37 mL, P = .003), longer duration of postoperative abdominal
      drainage (9.0 +/- 12.9 days versus 3.4 +/- 2.1 days, P = .041), more patients
      converted to open cholecystectomy (OC; 19.1% versus 4.1%, P = .021), more OC
      patients (14.9% versus 0%, P = .005), more patients with gangrenous cholecystitis
      (40.4% versus 8.2%, P < .001), more cholecystitis patients with perforation
      (12.8% versus 0%, P = .012), a higher incidence of respiratory failure (14.8%
      versus 2.0%, P = .029), more admissions to the intensive care unit (ICU) (21.3%
      versus 2.0%, P = .003), and longer postoperative hospital stays (8.2 +/- 3.2 days
      versus 11.6 +/- 4.6 days, P < .001) in the PTGBD + DC group. In addition, there
      were statistically more OC patients (63.2% versus 14.3%, P = .001) in the
      nonbiliary surgeon group than the biliary surgeon group. CONCLUSION(S): In
      patients with moderate (grade II) acute cholecystitis, PTGBD and EC were highly
      efficient in resolving cholecystitis. DC patients after PTGBD had better outcomes
      with a lower rate of OC, less intraoperative bleeding, shorter duration of
      postoperative abdominal drainage, shorter hospital stays after cholecystectomy, a
      lower incidence of respiratory failure, fewer admissions to the ICU than EC, and
      reversed the pathologic process affecting the gallbladder. The total
      postoperative hospital stay was longer in the PTGBD + DC group.

PMID- 29658840
TI  - Neuropharmacological and molecular docking studies of xanthones from Swertia
      corymbosa.
AB  - Anxiety represents a public health problem consistently found to be the most
      prevalent class of mental disorders among people of all ages. Xanthones possess
      many biological properties, including neuroprotective, antioxidant or
      antidepressant-like. In this study, we aimed to investigate anxiolytic-like
      antidepressant and anticonvulsant properties of isolated xanthones from Swertia
      corymbosa. We evaluated anxiolytic-like activity of compounds 1-3 in the mouse
      elevated plus maze (EPM) and open field test (OF). We examined the influence on
      locomotor activity in mouse to determine if the effect observed in the
      actophotometer specific. We used step-through rotarod tests to evaluate the motor
      function and muscle grip. Compounds 1-3 significantly induced an increase in the
      number of entries into open arms and a decrease in time spent into closed arms at
      the dose of 50 mg/kg body weight (BW). The compounds also induced increase of
      rearing and decrease grooming at the doses of 25 and 50 mg/kg BW during the OF
      test. In addition, compounds induced a significant increase of time taken to
      enter at the center of the experimental set at the dose of 50 mg/kg BW during the
      open field test. The compounds 1-3 significantly delayed the onset as well as
      decreased the pentylenetetrazole and isoniazid-induced seizure tests. Compound 3
      pretreatment significantly improved survivals in pentylenetetrazole and isoniazid
      induced seizure tests. In silico studies reveal its possible mechanism of action
      shed on light to develop novel drugs against CNS disorders.

PMID- 29658841
TI  - Genetic Structure of Zymoseptoria tritici in Northern France at Region, Field,
      Plant, and Leaf Layer Scales.
AB  - Population genetic structure of the worldwide-distributed wheat pathogen
      Zymoseptoria tritici has been extensively studied at large geographical scales,
      but to a much less extent at small or local spatial scales. A total of 627 single
      conidial fungal isolates were sampled from several locations in northern France
      (Hauts-de-France Region) to assess fungal genetic structure at region, field,
      plant, and leaf layer scales, using highly polymorphic microsatellite markers and
      mating type idiomorphs. Important and overall similar levels of both gene and
      genotype diversities (gene diversity values of >=0.44 and haplotype frequencies
      of >=94%) were found at all the examined scales. Such rates of diversity are
      likely due to an active sexual recombination in the investigated areas, as
      revealed by equal proportions of the two mating types scored in all sampled
      populations. Interestingly, a rare occurrence of clones among lesions from a same
      leaf, as well as among leaves from different plant leaf layers (e.g., upper
      versus lower leaves), was highlighted, indicating that ascospores contribute much
      more than expected to Z. tritici epidemics, compared with pycnidiospores.
      Population structure and analyses of molecular variance revealed significant
      genetic differentiation at the regional scale (GST = 0.23) and, as expected, not
      at the other more local scales (GST <= 0.01). Further analyses using Bayesian and
      unweighted neighbor-joining statistical methods detected six genetic clusters
      within the regional population, overall distributed according to the locations
      from which the isolates were sampled. Neither clear directional relative
      migration linked to the geographical distribution of the locations, nor isolation
      by distance, were observed. Separate evolutionary trajectories caused by
      selection and adaptations to habitat heterogeneity could be the main forces
      shaping such structuration. This study provides new insights into the
      epidemiology and the genetic structure of Z. tritici at small local and, for the
      first time, at single plant and leaf layer scales. Such findings would be helpful
      in implementing effective control strategies.

PMID- 29658842
TI  - Pathogenic Streptomyces spp. Abundance Affected by Potato Cultivars.
AB  - Potato cultivars vary in their tolerance to common scab; however, how they affect
      common scab-causing Streptomyces spp. populations over time is poorly understood.
      This study investigated the effects of potato cultivar on pathogenic Streptomyces
      spp. abundance, measured using quantitative PCR, in three spatial locations in a
      common scab-infested field: (i) soil close to the plant (SCP); (ii) rhizosphere
      soil (RS); and (iii) geocaulosphere soil (GS). Two tolerant (Gold Rush,
      Hindenburg) and two susceptible cultivars (Green Mountain, Agria) were tested.
      The abundance of pathogenic Streptomyces spp. significantly increased in late
      August compared with other dates in RS of susceptible cultivars in both years.
      Abundance of pathogenic Streptomyces spp., when averaged over locations and time,
      was significantly greater in susceptible cultivars compared with tolerant
      cultivars in 2014. Principal coordinates analysis showed that SCP and RS soil
      properties (pH, organic carbon, and nitrogen concentrations) explained 68 and 76%
      of total variation in Streptomyces spp. abundance among cultivars in 2013,
      respectively, suggesting that cultivars influenced common scab pathogen growth
      conditions. The results suggested that the genetic background of potato cultivars
      influenced the abundance of pathogenic Streptomyces spp., with five to six times
      more abundant Streptomyces spp. in RS of susceptible cultivars compared with
      tolerant cultivars, which would result in substantially more inoculum left in the
      field after harvest.

PMID- 29658843
TI  - Perceptions of Midwestern Crop Advisors and Growers on Foliar Fungicide Adoption
      and Use in Maize.
AB  - Foliar fungicide use in hybrid maize in the United States was rare before 2000.
      The decade from 2000 to 2010 saw foliar fungicides increasingly applied to maize
      in the absence of appreciable disease pressure, a practice seemingly at odds with
      integrated pest management philosophy. Yet, it is commonly believed that growers
      do not employ management strategies unless there are perceived benefits. Maize
      (corn) growers (CGs) and certified crop advisors (CCAs) across four Midwestern
      states (Iowa, Illinois, Ohio, and Wisconsin) were surveyed to better understand
      their practices, values and perceptions concerning the use of foliar fungicides
      during 2005 to 2009. The survey results demonstrated the rapid rise in maize
      foliar fungicide applications from 2000 through 2008, with 84% of CGs who sprayed
      having used a foliar fungicide in maize production for the very first time during
      2005 to 2009. During 2005 to 2009, 73% of CCAs had recommended using a foliar
      fungicide, but only 35% of CGs sprayed. Perceived yield gains, conditional on
      having sprayed, were above the break-even point on average. However, negative
      yield responses were also observed by almost half of CCAs and a quarter of CGs.
      Hybrid disease resistance was a more important factor to economically successful
      maize production than foliar fungicides. Diseases as a yield-limiting factor were
      more important to CGs than CCAs. As a group, CGs were not as embracing of foliar
      fungicide as were CCAs, and remained more conservative about the perceived
      benefits to yield.

PMID- 29658844
TI  - Functional Interactions Between Major Rice Blast Resistance Genes, Pi-ta and Pi
      b, and Minor Blast Resistance Quantitative Trait Loci.
AB  - Major blast resistance (R) genes confer resistance in a gene-for-gene manner.
      However, little information is available on interactions between R genes. In this
      study, interactions between two rice blast R genes, Pi-ta and Pi-b, and other
      minor blast resistance quantitative trait loci (QTLs) were investigated in a
      recombinant inbred line (RIL) population comprising 243 RILs from a Cybonnet
      (CYBT) * Saber (SB) cross. CYBT has the R gene Pi-ta and SB has Pi-b. Ten
      differential isolates of four Magnaporthe oryzae races (IB-1, IB-17, IB-49, and
      IE-1K) were used to evaluate disease reactions of the 243 RILs under greenhouse
      conditions. Five resistance QTLs were mapped on chromosomes 2, 3, 8, 9, and 12
      with a linkage map of 179 single nucleotide polymorphism markers. Among them,
      qBR12 (Q1), was mapped at the Pi-ta locus and accounted for 45.41% of phenotypic
      variation while qBR2 (Q2) was located at the Pi-b locus and accounted for 24.81%
      of disease reactions. The additive-by-additive epistatic interaction between Q1
      (Pi-ta) and Q2 (Pi-b) was detected; they can enhance the disease resistance by an
      additive 0.93 using the 0 to 9 standard phenotyping method. These results suggest
      that Pi-ta interacts synergistically with Pi-b.

PMID- 29658845
TI  - Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden.
AB  - BACKGROUND: Nivolumab plus ipilimumab showed promising efficacy for the treatment
      of non-small-cell lung cancer (NSCLC) in a phase 1 trial, and tumor mutational
      burden has emerged as a potential biomarker of benefit. In this part of an open
      label, multipart, phase 3 trial, we examined progression-free survival with
      nivolumab plus ipilimumab versus chemotherapy among patients with a high tumor
      mutational burden (>=10 mutations per megabase). METHODS: We enrolled patients
      with stage IV or recurrent NSCLC that was not previously treated with
      chemotherapy. Those with a level of tumor programmed death ligand 1 (PD-L1)
      expression of at least 1% were randomly assigned, in a 1:1:1 ratio, to receive
      nivolumab plus ipilimumab, nivolumab monotherapy, or chemotherapy; those with a
      tumor PD-L1 expression level of less than 1% were randomly assigned, in a 1:1:1
      ratio, to receive nivolumab plus ipilimumab, nivolumab plus chemotherapy, or
      chemotherapy. Tumor mutational burden was determined by the FoundationOne CDx
      assay. RESULTS: Progression-free survival among patients with a high tumor
      mutational burden was significantly longer with nivolumab plus ipilimumab than
      with chemotherapy. The 1-year progression-free survival rate was 42.6% with
      nivolumab plus ipilimumab versus 13.2% with chemotherapy, and the median
      progression-free survival was 7.2 months (95% confidence interval [CI], 5.5 to
      13.2) versus 5.5 months (95% CI, 4.4 to 5.8) (hazard ratio for disease
      progression or death, 0.58; 97.5% CI, 0.41 to 0.81; P<0.001). The objective
      response rate was 45.3% with nivolumab plus ipilimumab and 26.9% with
      chemotherapy. The benefit of nivolumab plus ipilimumab over chemotherapy was
      broadly consistent within subgroups, including patients with a PD-L1 expression
      level of at least 1% and those with a level of less than 1%. The rate of grade 3
      or 4 treatment-related adverse events was 31.2% with nivolumab plus ipilimumab
      and 36.1% with chemotherapy. ical; CheckMate 227 ClinicalTrials.gov number,
      NCT02477826 .). CONCLUSIONS: Progression-free survival was significantly longer
      with first-line nivolumab plus ipilimumab than with chemotherapy among patients
      with NSCLC and a high tumor mutational burden, irrespective of PD-L1 expression
      level. The results validate the benefit of nivolumab plus ipilimumab in NSCLC and
      the role of tumor mutational burden as a biomarker for patient selection. (Funded
      by Bristol-Myers Squibb and Ono Pharmaceut

PMID- 29658846
TI  - Tobacco-Free Policies and Tobacco Cessation Systems at Health Centers Serving
      Lesbian, Gay, Bisexual, and Transgender Clients.
AB  - PURPOSE: LGBT populations have high rates of tobacco use. Health centers serving
      LGBT clients are an important source of care. The researchers aimed to assess the
      implementation of recommended systems-level tobacco cessation interventions at
      these health centers. METHODS: Using systematic searching, directories, and
      expert review, we identified health centers serving LGBT clients that provide
      primary care. We conducted phone-based, semi-structured interviews with
      administrators (n = 11) between September 2016 and March 2017 regarding
      implementation of the Clinical Practice Guideline, Treating Tobacco Use and
      Dependence: 2008 Update (the Guideline). Two authors confirmed saturation and two
      authors conducted thematic coding. RESULTS: Eight themes were identified,
      including clear evidence of systems-level procedures for asking about, advising
      on, and assessing tobacco use. Interviewees viewed tobacco use as important given
      existing disparities. However, there was room for improvement in the following
      areas: (1) Education for staff on tobacco cessation was ad hoc and not
      formalized; (2) materials and resources for tobacco cessation available in the
      center varied widely and changed when a staff champion arrived or left; (3) no
      point person was assigned to coordinate tobacco cessation efforts; and, (4)
      assessment of tobacco use as a vital sign is not consistent-some centers met
      meaningful use quality metrics (e.g., once or more in the past 24 months) instead
      of the Guideline recommendation (every visit). Addressing tobacco use competes
      with addressing other health risk behaviors. CONCLUSIONS: Administrators at
      health centers serving LGBT clients viewed tobacco use as an important issue.
      However, there was room for improvement in implementation of systems recommended
      in the Guideline. Targeted outreach is warranted to improve standardization of
      implementation and promote cessation of tobacco use.

PMID- 29658847
TI  - Non-Face-to-Face Chronic Care Management: A Qualitative Study Assessing the
      Implementation of a New CMS Reimbursement Strategy.
AB  - Diabetes and its comorbidities are leading causes of morbidity and mortality in
      the United States and disproportionately in Louisiana. Chronic care management
      (CCM) efforts, such as care coordination models, are important initiatives in
      mitigating the impact of diabetes, such as poorer health outcomes and increased
      costs. This study examined one such effort, the Centers for Medicare & Medicaid
      Services' non-face-to-face CCM reimbursement program, for patients with diabetes
      and at least 1 other chronic condition in Louisiana. This qualitative study
      included interviews with patients in this program and health care providers and
      system leaders implementing the program. Results include lessons learned from
      health system leadership relating to CCM design and implementation, challenges
      experienced, overlapping initiatives, perceived benefits, performance, billing,
      and health information technology. Another key finding is that co-pays seem to be
      a barrier to patient interest in participation in non-face-to-face CCM,
      especially given that the value of the program is not completely clear to
      patients. A common strategy to address this co-pay barrier is to target dual
      eligibles, as Medicaid will cover the co-pay. However, widespread use of such
      strategies may indirectly exclude individuals who need and may also benefit from
      non-face-to-face CCM.

PMID- 29658850
TI  - Healthy Communities-The Role of the School Nurse: Position Statement.

PMID- 29658849
TI  - Suicide Prevention for School Communities: An Educational Initiative for Student
      Safety.
AB  - A knowledge gap exists in school communities regarding suicide prevention and
      means reduction education. The article highlights two core interrelated topics:
      school nurse engagement in dialogue with students' families and the
      implementation of an innovative, community-based suicide prevention educational
      program at a suburban public school district. The authors provide an overview of
      the public health problem of suicide for students, current student challenges,
      role of the school nurse in suicide prevention, and a key gap in current school
      nursing practice. At the request of the school counselors and principal, an
      innovative suicide prevention educational program was initiated as a community
      based project at a large suburban public school district in Texas. The two
      overarching goals for this community-based collaboration are the following:
      school nurses will engage in frank, productive conversations with students'
      parents and families about suicidality concerns and increase the school
      community's knowledge about suicide prevention. This school community knowledge
      includes effective risk mitigation and means reduction strategies to better
      manage suicidality in students. Ultimately, this ongoing family and school
      community collaboration aims to prevent student deaths by suicide.

PMID- 29658851
TI  - An Eye on Vision: Five Questions About Vision Screening and Eye Health.
AB  - Current evidence-based and best-practice vision screening and eye health
      approaches, tools, and procedures are the result of revised national guidelines
      in the past 3 years and advances in research during the past 18 years. In
      providing answers to the five questions in this article, the National Center for
      Children's Vision and Eye Health at Prevent Blindness used published, peer
      reviewed research; vision screening and eye health national guidelines; and
      consensus-based best practices from eye care professionals and public health
      experts. The answers may differ from your state or district vision screening
      guidelines and mandates. This is the second installment of the "An Eye on Vision"
      frequently asked questions section that will appear in future editions of NASN
      School Nurse. To review the first installment, see the March 2018 edition of NASN
      School Nurse. The authors encourage vision screeners to submit their vision
      screening and eye health questions to the email address that appears at the end
      of this article.

PMID- 29658848
TI  - Neoadjuvant PD-1 Blockade in Resectable Lung Cancer.
AB  - BACKGROUND: Antibodies that block programmed death 1 (PD-1) protein improve
      survival in patients with advanced non-small-cell lung cancer (NSCLC) but have
      not been tested in resectable NSCLC, a condition in which little progress has
      been made during the past decade. METHODS: In this pilot study, we administered
      two preoperative doses of PD-1 inhibitor nivolumab in adults with untreated,
      surgically resectable early (stage I, II, or IIIA) NSCLC. Nivolumab (at a dose of
      3 mg per kilogram of body weight) was administered intravenously every 2 weeks,
      with surgery planned approximately 4 weeks after the first dose. The primary end
      points of the study were safety and feasibility. We also evaluated the tumor
      pathological response, expression of programmed death ligand 1 (PD-L1),
      mutational burden, and mutation-associated, neoantigen-specific T-cell responses.
      RESULTS: Neoadjuvant nivolumab had an acceptable side-effect profile and was not
      associated with delays in surgery. Of the 21 tumors that were removed, 20 were
      completely resected. A major pathological response occurred in 9 of 20 resected
      tumors (45%). Responses occurred in both PD-L1-positive and PD-L1-negative
      tumors. There was a significant correlation between the pathological response and
      the pretreatment tumor mutational burden. The number of T-cell clones that were
      found in both the tumor and peripheral blood increased systemically after PD-1
      blockade in eight of nine patients who were evaluated. Mutation-associated,
      neoantigen-specific T-cell clones from a primary tumor with a complete response
      on pathological assessment rapidly expanded in peripheral blood at 2 to 4 weeks
      after treatment; some of these clones were not detected before the administration
      of nivolumab. CONCLUSIONS: Neoadjuvant nivolumab was associated with few side
      effects, did not delay surgery, and induced a major pathological response in 45%
      of resected tumors. The tumor mutational burden was predictive of the
      pathological response to PD-1 blockade. Treatment induced expansion of mutation
      associated, neoantigen-specific T-cell clones in peripheral blood. (Funded by
      Cancer Research Institute-Stand Up 2 Cancer and others; ClinicalTrials.gov
      number, NCT02259621 .).

PMID- 29658853
TI  - Moving an Evidence-Based Policy Agenda Forward: Leadership Tips From the Field.
AB  - Advancing evidence-based policy change is a leadership challenge that nurses
      should embrace. Key tips to ensure that evidence-based policy changes are
      successful at the individual, community, and population levels are offered to
      help nurses through the change process. The public trust in the nursing
      profession is a leverage point that should be used to advance the use of
      evidence, expedite change, and improve health for students and across
      communities.

PMID- 29658852
TI  - Evidence-based Practice: Making the Research Relevant to Your Situation-CLUE #4:
      Apply.
AB  - Evidence-based practice (EBP) is often thought to be synonymous with research and
      literature. This article focuses on the fourth step in the EBP process: Apply. In
      this step, we fully integrate the EBP Venn diagram, which illustrates that EBP
      occurs at the intersection of evidence and data, clinical expertise and
      resources, and population's values and cultures. Only when school nurses include
      each component into their practice decision will true EBP occur.

PMID- 29658854
TI  - School Nurses: Leading the Development of Healthy Communities.

PMID- 29658855
TI  - The Enhanced Nurse Licensure Compact (eNLC): Unlocking Access to Nursing Care
      Across the Nation.
AB  - Nurses, including school nurses, may reside in a state with compact licensing. On
      July 20, 2017, an enhanced Nurse Licensure Compact (eNLC) was enacted with
      implementation beginning on January 19, 2018. Nurses must be knowledgeable about
      the status of their state's participation in the compact licensure, both their
      state of residence and their state of practice. Nurses must also be knowledgeable
      about what is entailed in compact licensure. This brief article provides basic
      information about compact licensing, along with considerations about nursing
      delegation, for the practicing school nurse.

PMID- 29658857
TI  - Editorial: Perioperative Pharmacological Management: From Prescription
      Medications to Dietary Supplements.

PMID- 29658859
TI  - Identification and genetic characterization of equine Pegivirus in China.
AB  - In 2013, two new viruses, equine pegivirus (EPgV) and Theiler's disease
      associated virus (TDAV), both belonging to the genus Pegivirus within the family
      Flaviviridae, were identified. To investigate the geographical distribution and
      genetic diversity of these two viruses in China, we screened EPgV and TDAV
      infection in imported race horses and Chinese work horses by using reverse
      transcription polymerase chain reaction (RT-PCR). EPgV was detected in 10.8 %
      (8/74) of the total horses tested, with a prevalence of 5.8 and 22.7 % in the
      race horses and work horses, respectively. No TDAV infection was found. A near
      full-length genome sequence of EPgV was obtained that showed an identity of 89.5
      90.6 % at the nucleotide level and 98.1-98.3 % at the amino acid level with an
      American strain, C0035, and another Chinese strain, LW/216, respectively.
      Phylogenetic analysis showed two different clusters of the sequences from the
      race horses and work horses, indicating a difference in virus origin. Our results
      demonstrated a higher positive rate of EPgV in the Chinese work horses than in
      the imported race horses, a moderate genetic diversity of EPgV strains worldwide
      and possibly no liver pathogenesis for EPgV infection.

PMID- 29658858
TI  - Carboxylicivirga sediminis sp. nov., isolated from coastal sediment.
AB  - A yellow-pigmented bacterial strain (JR1T) isolated from a sediment sample was
      subjected to a taxonomic study, based on phenotypic, genetic and physiological
      characterization. Here, we describe the cultivation and characteristics of strain
      JR1T, a novel member of the genus Carboxylicivirga in the family
      Marinilabiliaceae. Cells of strain JR1T were rod-shaped, Gram-stain-negative, non
      motile and facultatively anaerobic. The temperature range for growth was 15-42 
      degrees C (optimum, 33  degrees C) and the pH range for growth was pH 6.0-8.5
      (optimum, pH 7.0-7.5). Growth occurred in the presence of 0.0-10.0 % (w/v) NaCl
      (optimum 2.0-3.0 %). 16S rRNA gene sequence analysis produced results with 97.4 %
      similarity to Carboxylicivirga taeanensisMEBiC 08903T, 96.8 % similarity to
      Carboxylicivirga mesophilaMEBiC 07026T, 94.9 % similarity to Carboxylicivirga
      linearis FB218T and 94.6 % similarity to Carboxylicivirga flava Q15T. The DNA G+C
      content was 42.3 mol% and the major fatty acids were iso-C15 : 0, C15 : 0,
      anteiso-C15 : 0, C17 : 1omega6c and iso-C17 : 0-3OH. The major polar lipids
      detected were phosphatidylethanolamine and two unidentified lipids; the major
      respiratory quinone detected was MK-7. The results of the phenotypical,
      phylogenetic and biochemical analyses between the study strain and some related
      type strains indicated that this strain represent a novel species of the genus
      Carboxylicivirga within the family Marinilabiliaceae, for which the name
      Carboxylicivirga sediminis sp. nov. is proposed. The type strain is JR1T (=MCCC
      1K03323T=KCTC 52869T).

PMID- 29658860
TI  - Pressure Support Breaths Triggered by Total Artificial Heart in Invasive and Non
      Invasive Mechanical Ventilation.
AB  - Because of the risks associated with extended mechanical ventilation, it is
      desirable to extubate patients as early as possible. However, weaning patients
      from mechanical ventilation too early has risks associated with it as well. Thus,
      it is important to note that in the two cases presented here, pressure-supported
      breaths were falsely triggered by a patient's a Syncardia(r) total artificial
      heart (TAH), influencing decisions about weaning the patient from mechanical
      ventilation.

PMID- 29658861
TI  - Monster Lung Cavity in a Heart Transplant Recipient.
AB  - Invasive mucormycosis infections occur in less than 1% of recipients of
      orthotopic heart transplants. Given the angioinvasive nature of these infections,
      the mortality rate is high. Little literature exists regarding the presentation
      and management of these infections. We present a case of a patient who developed
      an infection after orthotopic heart transplant, describe the successful
      multidisciplinary management surrounding his care, and review the available
      literature regarding mucormycosis infections in heart transplant recipients.

PMID- 29658862
TI  - Progress in Gene Therapy for Chronic Heart Failure.
AB  - Chronic heart failure (CHF) is still the leading cause of morbidity and mortality
      worldwide, and carries with it large economic and social burdens. Although steady
      and substantial progress has been made in reducing mortality from heart failure
      using conventional treatments, novel pharmacologic and surgical interventions
      have not been effective in extending five year survival rates. Therefore, it is
      necessary to explore new therapies. Gene therapy was introduced in 1970s with the
      development of recombinant DNA technology. Due to recent progress in the
      understanding of myocardial metabolism and application of vector based gene
      transfer strategies in animal models and initial clinical trials, gene therapy
      possibly affords an ideal treatment alternative for CHF. In last 2 decades, much
      research has been done on gene therapy, using various genes, signal transduction
      passages and delivery methods to treat advanced heart failure. Current research
      in ischemic heart disease (IHD) mainly focuses on stimulating angiogenesis,
      modifying the coronary vascular environment, and improving the vascular
      endothelial function with localized gene coated catheters and stents. Compared
      with standard ischemic heart disease treatment, the main goal of gene therapy for
      CHF is to inhibit apoptosis, reduce the undesirable remodeling and increase
      contractility through the most efficient cardiomyocyte transfection [Katz 2012a].
      In this paper, we review various gene transfer technologies in ischemic heart
      disease and heart failure models, and discuss the advantages and disadvantages of
      these strategies in vector-mediated cardiac gene delivery, with the main focus on
      the high efficiency approach of a molecular cardiac surgery delivery system.

PMID- 29658856
TI  - Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer.
AB  - BACKGROUND: First-line therapy for advanced non-small-cell lung cancer (NSCLC)
      that lacks targetable mutations is platinum-based chemotherapy. Among patients
      with a tumor proportion score for programmed death ligand 1 (PD-L1) of 50% or
      greater, pembrolizumab has replaced cytotoxic chemotherapy as the first-line
      treatment of choice. The addition of pembrolizumab to chemotherapy resulted in
      significantly higher rates of response and longer progression-free survival than
      chemotherapy alone in a phase 2 trial. METHODS: In this double-blind, phase 3
      trial, we randomly assigned (in a 2:1 ratio) 616 patients with metastatic
      nonsquamous NSCLC without sensitizing EGFR or ALK mutations who had received no
      previous treatment for metastatic disease to receive pemetrexed and a platinum
      based drug plus either 200 mg of pembrolizumab or placebo every 3 weeks for 4
      cycles, followed by pembrolizumab or placebo for up to a total of 35 cycles plus
      pemetrexed maintenance therapy. Crossover to pembrolizumab monotherapy was
      permitted among the patients in the placebo-combination group who had verified
      disease progression. The primary end points were overall survival and progression
      free survival, as assessed by blinded, independent central radiologic review.
      RESULTS: After a median follow-up of 10.5 months, the estimated rate of overall
      survival at 12 months was 69.2% (95% confidence interval [CI], 64.1 to 73.8) in
      the pembrolizumab-combination group versus 49.4% (95% CI, 42.1 to 56.2) in the
      placebo-combination group (hazard ratio for death, 0.49; 95% CI, 0.38 to 0.64;
      P<0.001). Improvement in overall survival was seen across all PD-L1 categories
      that were evaluated. Median progression-free survival was 8.8 months (95% CI, 7.6
      to 9.2) in the pembrolizumab-combination group and 4.9 months (95% CI, 4.7 to
      5.5) in the placebo-combination group (hazard ratio for disease progression or
      death, 0.52; 95% CI, 0.43 to 0.64; P<0.001). Adverse events of grade 3 or higher
      occurred in 67.2% of the patients in the pembrolizumab-combination group and in
      65.8% of those in the placebo-combination group. CONCLUSIONS: In patients with
      previously untreated metastatic nonsquamous NSCLC without EGFR or ALK mutations,
      the addition of pembrolizumab to standard chemotherapy of pemetrexed and a
      platinum-based drug resulted in significantly longer overall survival and
      progression-free survival than chemotherapy alone. (Funded by Merck; KEYNOTE-189
      ClinicalTrials.gov number, NCT02578680 .).

PMID- 29658863
TI  - Swallow Syncope After Whiplash Neck Injury.
AB  - Swallow syncope is a rare dysautonomic syndrome characterized by temporary loss
      of consciousness upon swallowing solid foods or liquids, displaying primarily in
      individuals with an underlying structural or functional esophageal or cardiac
      pathology. However, the evidence also suggests that isolated vagal dysfunction or
      abnormal reactions of esophageal mechanoreceptors after mechanical irritation,
      demyelination, or trauma can potentially evoke  a cardioinhibitory response or
      vasodepression upon swallowing. We present a case of a 49-year-old otherwise
      healthy female patient who developed swallow syncope two weeks after whiplash
      neck injury acquired in a rear-end collision. After no evident anatomical and/or
      functional cardiac or esophageal pathology was diagnosed using several diagnostic
      procedures, the final diagnosis was confirmed by a provocative tilt-table test
      while ingesting solid food. Subsequently, a dual-chamber pacemaker was implanted,
      relieving the patient from troublesome symptoms. Abnormal reactions of esophageal
      mechanoreceptors to stimuli associated with food ingestion and/or dysfunction of
      afferent and efferent vagal fibers due to stretch injury and related neck trauma
      (acquired during the car accident) may be the leading pathophysiological
      mechanisms of swallow syncope in our patient.

PMID- 29658864
TI  - Right Ventricular Perforation by a Defibrillator Lead Migrating to the Left
      Breast.
AB  - Cardiac perforation after an ICD implantation is a rare complication, with a
      reported incidence between 0.6-5.2%. Its manifestation might be acute, subacute,
      or delayed, with an acute perforation occurring within the first 24 hours after
      implantation, frequently accompanied by severe clinical signs, while subacute and
      delayed perforations have a more benign progression. Here, we report a case of a
      69-year old patient with an acute right ventricular perforation by a
      defibrillator lead migrating all the way through the pericardium and thoracic
      wall into the left breast, with an unusually mild and benign clinical course,
      delaying prompt diagnosis and postponing subsequent surgical treatment. Heart
      perforation with a defibrillator electrode is a rare but dangerous complication,
      which may lead to pacing failure, cardiac tamponade, cardiogenic shock, and even
      death. Even with a benign clinical course, one must think of cardiac wall
      perforation at any time after device implantation, and a contrast enhanced
      computer tomography (CTA) must be performed if perforation is suspected. At re
      implantation, the lead should be located at a different anatomical position
      within the RV, preferably at the interventricular septal site, and manipulation
      of the injury site within the RV avoided.

PMID- 29658865
TI  - Hemodynamic Consequence of Different Pacing Modes after Aortic Valve Replacement.
AB  - OBJECTIVES: Ventricular pacemaker stimulation may cause deterioration of
      hemodynamics in patients with left-ventricular hypertrophy following aortic valve
      replacement. Since the diastolic function is often impaired, it remains unclear
      which heart rate best optimizes cardiac output. Low heart rates are suggested to
      treat impaired diastolic function chronically, but it is possible that cardiac
      output may be augmented by increasing the heart rate in patients with a fixed
      stroke volume (SV). The aim of this study is the identification of the best
      pacing mode and heart rate for the surrogate parameter SV and cardiac index(CI)
      in patients with left ventricular hypertrophy. METHODS: Various pacemaker
      stimulation modes and different heart rates, as well as their influence on
      hemodynamics, were tested following aortic valve replacement in 48 patients with
      severe left-ventricular hypertrophy (Intraventricular septum (IVS)>1.5 cm) and
      aortic stenosis. SV and cardiac output were recorded by pulse curve analysis.
      Four modes of stimulation (right ventricular pacemaker stimulation (DDDright),
      left ventricular pacemaker stimulation (DDDleft), biventricular pacemaker
      stimulation (DDDbi), atrial pacemaker stimulation (AAI)) were documented at five
      different rates (60, 80, 100, 120, 140 beats/min) and three different
      postoperative time points (intraoperatively, 3h and 24h postoperatively).
      RESULTS: The highest CI was found at linear rates between 60 to 140bpm. AAI was
      the best mode of stimulation in the majority of cases (35%), but in others,
      either left, right and/or biventricular stimulation was found to be better (15%).
      SV showed a u-shaped trend with a peak at 100 beats/min. CONCLUSION: An increase
      in the heart rate does not lead to a notable drop in SV postoperatively in left
      ventricular hypertrophy; hence a rise in cardiac output can be anticipated up to
      a rate of 100 beats/min. A standardized response in terms of an ideal pacemaker
      stimulation mode could not be identified.

PMID- 29658866
TI  - Mechanical Valve Replacement for Congenital Heart Disease Complicated by Native
      Pulmonary Valve Endocarditis: A Case Report and Literature Review.
AB  - Congenital heart disease (CHD) is one of the most common risk factors for
      infective endocarditis. However, it is rare to find a CHD patient complicated by
      isolated pulmonary valve endocarditis. Here, we report an adult patient with
      congenital heart disease complicated by native pulmonary valve endocarditis who
      underwent a mechanical valve replacement. We also review previous literature to
      examine key points in the treatment of such patients.

PMID- 29658867
TI  - Repair of Partial Anomalous Pulmonary Venous Connection: A Rare Case Evaluated by
      Multi-Slice Computed Tomographic Angiography.
AB  - Partial anomalous pulmonary venous connection (PAPVC) is an uncommon congenital
      heart disease, which may be difficult to identify and often remains undiagnosed.
      Accurate diagnosis of major aortopulmonary collaterals and partial anomalous
      pulmonary venous drainage in patients with congenital heart disease is important
      but problematic. The goal of this publication is to present the diagnosis and
      surgical repair of this rare pathology in an eight-year-old boy. Atrial septal
      defect was found by echocardiography, but no anomalous pulmonary vein was found.
      However, multi-slice computed tomographic angiography (MSCTA) revealed that the
      isolated right superior pulmonary vein was replaced by right superior pulmonary
      vein 1 (RSPV1), right superior pulmonary vein 2 (RSPV2) and right superior
      pulmonary vein 3 (RSPV3), which connected to the superior vena cava (SVC), the
      orifice of SVC, and the left atrium, respectively. The patient underwent the
      repair of PAPVC with division of the SVC and re-implantation on the right atrial
      appendage to restore normal systemic venous drainage. Postoperative course was
      uneventful. In conclusion, PAPVC is a rare congenital cardiac pathology. MSCTA
      could contribute to an accurate anatomic and functional definition of this
      variant.

PMID- 29658868
TI  - Serum Levels of miR-155, miR-326, and miR-133b as Early Diagnostic Biomarkers for
      the Detection of Human Acute Heart Allograft Rejection in Comparison with Serum
      Cardiac Troponin T.
AB  - BACKGROUND: Acute heart allograft rejection occurs as a result of antibody
      mediated rejection that presents during the first month after transplantation.
      Finding a non-invasive biomarker is essential for diagnosis of heart allograft
      rejection. In this research, we intended to compare expression levels of several
      microRNAs across cardiac troponin T levels between rejected patients (who died
      before one month following transplantation), non-rejected patients (who survived
      for at least one month after transplantation), and non-transplanted patients
      (CABG surgery patients). METHODS: Serum levels of miR-155, miR-326, and miR-133b
      were evaluated by the q-RT-PCR method. Furthermore, cardiac troponin T levels
      were measured by a highly sensitive electrochemiluminescence assay. Finally, the
      data were analyzed by independent sample t-test using SPSS 21(r) computer
      software. Results: It was observed that miR-326 and miR-155 expression levels
      increased after 24h and 72h of surgery in rejected patients compared with the two
      other groups, but these increases were not statistically significant. Moreover,
      the decrease in miR-133b expression level was non-significant after
      transplantation in the rejected group compared with the non-rejected group.
      However, cTnT levels in rejected patients increased significantly compared with
      the other groups (P < .05). After ROC curve analysis, the cTnT marker with the
      most area under the curve (AUC = 1.00, 95% confidence interval, 1.00 to 1.00; P =
      .006), had the best discriminatory power, and among microRNAs, miR-326 had the
      largest area under curve (AUC = 0.81), and consequently the highest
      discriminatory power. CONCLUSIONS: We demonstrated that troponin T can be a more
      efficient biomarker than miRNAs for early prediction of human death caused by
      acute heart rejection, and the ROC curves analysis verified this finding.

PMID- 29658869
TI  - Predictive Model for Secundum Atrial Septal Defect Closure with Pulmonary Artery
      Hypertension in Adult: When to Close.
AB  - BACKGROUND: Secundum atrial septal defect (SASD) closure is contraindicated in
      the presence of severe pulmonary artery hypertension (PAH). However, there is no
      consensus on the threshold of severe PAH, in terms of mean pulmonary artery
      pressure (mPAP), which would contraindicate for defect closure surgery in adults.
      Furthermore, PAH can persist, or even increase in severity, after the closure.
      The aim of this study was to produce a predictive model correlating mPAP in adult
      SASD patients with PAH after defect closure surgery. Methods: Between January
      2014 and March 2017, 29 consecutive adult SASD patients who had PAH and underwent
      defect closure surgery were included in the study. Age, right atrium (RA)
      dimension, right ventricle (RV) dimension, and mPAP before surgery were analyzed
      using multiple regression to produce the model. RESULTS: Multiple regression
      produced the following model: mPAP prediction = (0.24)(Age) + (0.06)(mPAP before
      surgery) + (0.17)(RA dimension) + (0.47)(RV dimension) - 13.79 (P = .0008). The
      mPAP prediction was compared to mPAP of the patients six to nine months after
      surgery, and showed no significant difference (P = .9562). Conclusion: In adult
      SASD patients with PAH, our model can significantly predict the mPAP after the
      closure. If the predicted mPAP is within its normal range, the closure is
      indicated.

PMID- 29658870
TI  - Descending Thoracic Aortic Aneurysm Rupture Treated with Thoracic Endovascular
      Aortic Repair in a Patient with Peripheral Artery Disease.
AB  - Descending thoracic aortic aneurysm rupture is a life-threatening disease
      associated with high rates of morbidity and mortality. Treatment in these cases
      is a surgical emergency. Less invasive therapies for the treatment of this
      pathology have been developed over time. For descending thoracic aneurysm
      rupture, endovascular stent grafting is less invasive, life-saving, and a unique
      alternative to open repair. However, this approach is subject to anatomical and
      logistic limitations. The purpose of the present study is to report a case of an
      emergency endovascular repair for a ruptured thoracic aortic aneurysm in a
      patient with peripheral arterial disease, and to discuss some important issues
      related to this approach. Severe calcifications were discovered in this patient
      on both iliac arteries, and the remaining circulated lumen was less than 2 to 3
      mm. Unfortunately, only catheter insertion into the left iliac artery for
      angiography was able to determine the development of a dissection in the arterial
      wall. We decided to dilate both iliac arteries with partial stabilization of the
      dissection on the right iliac artery which allowed us to successfully continue
      the endovascular procedure. After 24 hours, the patient experienced right limb
      ischemia, and revascularization of the affected limb was achieved by performing a
      right axillofemoral bypass.

PMID- 29658872
TI  - Reoperative Cardiac Surgery - Part II.
AB  - The preparation for a reoperative cardiac surgical case was covered in Part I of
      this two part review [Tribble 2018]. Part II will cover primarily intraoperative
      strategies and techniques.  As noted in Part I, there has been surprisingly
      little written about the strategies and techniques of reoperative cardiac
      surgery. Thus, the goal of this two-part review is to collect and collate some of
      the lessons, abjurations, and tenets related to reoperative cardiac surgery that
      may be valuable to cardiac surgeons, especially those in training or early in
      their careers.Some time-honored admonitions that can apply to all complex
      operations, often enunciated by "old salts," bear repeating:*  Everything
      matters. Nothing is neutral.*  Some say that a "life or death" decision is made,
      on average, every 10 seconds during cardiac surgery. *  If something can go
      wrong, presume that it will.*  If it seems absolutely impossible for something to
      go wrong, it will anyway, at least some of the time.*  When something does go
      wrong, it generally does so all at once.*  If what you are doing is working, keep
      on doing it. If it ain't working, do something else.

PMID- 29658871
TI  - New-Onset Ventricular Arrhythmias in Patients with Left Ventricular Dysfunction
      after Coronary Surgery: Incidence, Risk Factors, and Prognosis.
AB  - BACKGROUND: The incidence, risk factors, and long-term prognosis of new-onset
      ventricular tachycardia (VT) and ventricular fibrillation (VF) after coronary
      artery bypass graft surgery (CABG) in patients with impaired left ventricular
      function have not been thoroughly examined. Methods: This study enrolled 612
      consecutive patients with impaired left ventricular function (ejection fraction
      <50%) undergoing CABG at a single institution between March, 1996, and September,
      2015. Outcomes were analyzed and compared, including in-hospital mortality and
      long-term survival. After a propensity-score, matching was performed to adjust
      for differences between the two cohorts. Factors significantly associated with
      VT/VF were also investigated using multivariate logistic regression. RESULTS: Of
      the 600 patients included in the analyses, 92 (15.3%; 95% confidence interval
      [CI] 12.5-18.3%) had new-onset VT/VF postoperatively. Before propensity matching,
      patients with postoperative VT/VF were more likely to have renal failure, intra
      aortic balloon pump support, lower preoperative ejection fraction (EF), and a
      larger left ventricle than those without VT/VF. Multivariate regression
      identified three preoperative risk factors and one protective factor that were
      independently associated with new-onset VT/VF: previous renal failure (odds ratio
      [OR] 4.42, P = .02), left ventricular end-diastolic dimension enlargement (OR
      1.83, P = .03), ejection fraction (OR 1.88, P = .02 for EF >=30 and <40% versus
      >=40% and <50%; OR 5.46, P = .00 for EF <30% versus >=40% and <50%), and
      preoperative beta-blockers (OR 0.58, P = .03). The median follow-up time was 46.6
      months. In the propensity-matched cohorts, survival for patients who had in
      hospital VT/VF was lower than that of the non-VT/VF group (89.9% versus 97.6%; P
      < .05). CONCLUSION: This study shows a high incidence of new-onset VT/VF after
      CABG in patients with impaired left ventricular function. The early and long-term
      survival rates were significantly lower in the VT/VF group. Preoperative renal
      failure, left ventricular end-systolic dimension enlargement, and the severity of
      left ventricular function were independently associated with the development of
      new-onset VT/VF after CABG surgery. Preoperative use of beta-blocker was proved
      to be protective in reducing both VT/VF incidence and in-hospital mortality in
      CABG patients with impaired left ventricular function following CABG. When
      considering these data, a prescription of beta-blockers is prognostically
      indicated to CABG patients, especially those with new-onset VT/VF
      postoperatively.

PMID- 29658873
TI  - A Prototype Lip Balm: Summary of Three Dermatological Studies Demonstrating
      Safety and Acceptability for Sensitive Skin.
AB  - Data were generated from three studies to assess the tolerability and
      acceptability of a prototype cosmetic lip balm. Dermatological assessments of
      topical compatibility (primary and cumulative irritability and sensitization),
      photoirritant and topical photosensitizer potential, and acceptability for safe
      use of a prototype cosmetic lip balm on sensitive skin are summarized. In Study
      1, the product was applied to the volunteers' backs under a semiocclusive patch
      followed by patch removal/reapplication over 6 weeks to assess the irritant and
      allergic potential of the product. Dermatological assessments were performed at
      the beginning and end of the study or when there was evidence of positivity or
      adverse event. Study 2 was conducted by applying the product to the volunteers'
      backs under a semiocclusive patch, followed by patch removal/reapplication and
      irradiation of the test area with ultraviolet A (UVA) radiation at various
      intervals over 5 weeks. Dermatological assessments were performed to assess the
      product's role in the induction of photoirritancy and photosensitization.
      Clinical and subjective assessments for acceptability were obtained during Study
      3 in volunteers with a diagnosis of sensitive skin and those who used the product
      as per instructions for use during the study period. The data generated from the
      three studies demonstrated no evidence of primary or cumulative dermal irritation
      or of dermal sensitization. In addition, no photoirritation potential or
      photosensitization potential was observed. As assessed by dermatologic monitoring
      and subject diary entries, the prototype lip balm did not cause irritation or
      sensitization reactions when used for 28 days in volunteers with a diagnosis of
      sensitive skin. Based on these findings, the prototype lip balm can be considered
      suitable for use for people with sensitive skin.

PMID- 29658874
TI  - Evaluation on an Optical Scanning Device for Skin Profile Measurement.
AB  - This paper describes experimental evaluations of an optical scanning device for
      skin surface recovery using multiple light source photometric stereo method. The
      portable optical device based on the principle of six-light photometric stereo
      was developed and subjected to evaluation and advancement through clinical trials
      for the purpose of monitoring skin conditions. As the device can provide
      objective topographic data for the description of the skin surface condition, the
      evaluation processes are mainly applied on skin in vitro and in vivo and compared
      with a commercial product, PRIMOS, which has been so far considered as a standard
      device used for skin surface measurement. The results of the experiment show that
      the topography measured by the device is significantly closer to that of the
      ground truth. Meanwhile, the new optical scanning device demonstrates better
      performance in measuring skin surface in vivo, superior to that of the PRIMOS.

PMID- 29658875
TI  - New Aspects of the Structure of Human Scalp Hair-II: Tubular Structure and
      Material Flow Property of the Medulla.
AB  - Asian scalp hair fibers were made thin by treatment with papain or sliced along
      the longitudinal axis or randomly cut by mechanical means. Optical microscopic
      observations of the resulting specimens indicated that (i) the medulla (M)
      consisted of two types of the M-surrounding cells which were linearly linked one
      another to form a tubular structure running through the fiber and (ii) the drum
      shaped vesicles containing small proteinous granules were neatly or sparsely
      stored within the tube. On the other hand, H+ and OH- ions were able to move
      spontaneously from one end to another through the M tube. Large molecules such as
      an anthocyanin dye (from purple sweet potato) were also capable of flowing
      through the M tube, especially rapidly when DC voltage was applied between the
      two ends of the hair fiber. The possible function of the M is briefly discussed
      in conjunction with the tubular structure and the material flow property.

PMID- 29658876
TI  - Use of L-Glutamic Acid in a New Enrichment Broth (R-TATP Broth) for Detecting the
      Presence or Absence of Molds in Raw Ingredients/Personal Care Product
      Formulations by Using an ATP Bioluminescence Assay.
AB  - The present study reports the effects of adding L-glutamic acid to a new
      enrichment broth designated as R-TATP broth, to promote the growth of slow
      growing mold microorganisms such as Aspergillus brasiliensis and Aspergillus
      oryzae, without interfering in the growth of other types of microorganisms. This
      L-glutamic acid containing enrichment broth would be particularly valuable in a
      rapid microbial detection assay such as an adenosine triphosphate (ATP)
      bioluminescence assay. By using this new enrichment broth, the amount of ATP
      (represented as relative light unit ratio after normalized with the negative test
      control) from mold growth was significantly increased by reducing the time of
      detection of microbial contamination in a raw ingredient or personal care product
      formulation from an incubation period of 48-18 h. By using L-glutamic acid in
      this enrichment broth, the lag phase of the mold growth cycle was shortened. In
      response to various concentrations of L-glutamic acid in R-TATP broth, there was
      an increased amount of ATP that had been produced by mold metabolism in an ATP
      bioluminescence assay. By using L-glutamic acid in R-TATP broth in an ATP
      bioluminescence assay, the presence of mold could be detected in 18 h as well as
      other types of microorganisms that may or may not be present in a test sample. By
      detecting the presence or absence of microbial contamination in 18 h, it is
      superior in comparison to a 48-96 h incubation period by using either a standard
      or rapid detection method.

PMID- 29658877
TI  - Simulation of the Elastin and Fibrillin in Non-Irradiated or UVA Radiated
      Fibroblasts, and Direct Inhibition of Elastase or Matrix Metalloptoteinases
      Activity by Nicotinamide or Its Derivatives.
AB  - Skin aging/photoaging is associated with altered the structure of collagen and
      elastin fibers, and increased activity of matrix metalloproteinases (MMP) and
      elastase. Nicotinamide and its derivatives, 2,6-dihydroxynicotinamide, 2,4,5,6
      tetrahydroxynicotinamide, and 3-hydroxypicolinamide (collectively niacin
      derivatives) stimulate fibrillar collagen and heat shock proteins in dermal
      fibroblasts. The goal of this research was to extend the understanding of the
      anti-skin aging mechanism of these niacin derivatives through the stimulation of
      elastin (at the protein and promoter levels), fibrillin (1 and 2) in
      nonirradiated or ultraviolet (UVA) radiated dermal fibroblasts, and through the
      direct inhibition of MMP (1, 3, and 9) and elastase activities. UVA radiation
      stimulated elastin and inhibited fibrillin-1 and fibrillin-2 in dermal
      fibroblasts. The niacin derivatives significantly stimulated the expression of
      elastin (transcriptionally), fibrillin-1 and fibrillin-2 in nonirradiated and UVA
      radiated fibroblasts, and directly inhibited MMP or elastase activity. Overall,
      the niacin derivatives, more so nicotinamide and 2,6-dihydroxynicotinamide, have
      anti-skin aging potential through the stimulation of elastin and fibrillin, and
      the direct inhibition of the extracellular matrix proteolytic enzymes.

PMID- 29658878
TI  - Comparing the Influence of Five Patch Types on the Result of a 12-Day Cumulative
      Irritancy Patch Test.
AB  - A 12-day cumulative irritancy patch test is available for predicting skin
      irritation potential. This study is important to determine the ideal patch type
      to be used in the irritancy patch test. This study was conducted to determine the
      cumulative skin irritation potential of five different patch types using
      predictive patch test techniques. Five types of patches were tested in a 12 day
      repeated insult test. The patch types were Hill Top Chamber occlusive, Finn
      Chamber occlusive, Band-Aid semiocclusive, Webril(r) semiocclusive, and Webril(r)
      occlusive. The test materials applied to the patches were cream, lotion, 2% bath
      cream, and controls of 1% sodium lauryl sulfate (1% SLS), respectively. A
      dermatologist performed the grading. The test results revealed that with cream,
      the cumulative scores of Hill Top Chamber occlusive, Finn Chamber occlusive, Band
      Aid semiocclusive, Webril(r) semiocclusive, and Webril(r) occlusive were 22, 27,
      16, 9, and 21, respectively; with lotion, the cumulative scores were 192, 200,
      192, 200, and 70, respectively; with 2% bath cream, the cumulative scores were
      523, 306, 523, 306, and 506, respectively; with 1% sodium dodecyl sulfate
      solution, the cumulative scores were 792, 801, 753, 526, and 841, respectively.
      Comparison of the five different patch types revealed that Webril(r)
      semiocclusive had the lowest cumulative irritation scores and incidence of
      adverse reactions. Comparison of the three test materials revealed that cream was
      the mildest material with the lowest cumulative irritation scores.

PMID- 29658879
TI  - The Rheological and Skin Sensory Properties of Cosmetic Emulsions: Influence of
      Thickening Agents.
AB  - Hydrophilic polymers are widely used in the cosmetics industry as thickening
      agents/rheology modifiers. These thickening agents have different chemical
      structures which affect the rheological properties, as well as the sensory
      attributes of the formula. Systematic study is important to determine the
      relationship among them. Six commonly used hydrophilic polymers, including
      cellulose derivatives and synthetic polymers, were used as thickening agents in a
      series of oil-in-water emulsions. The rheological properties were evaluated in
      relation to the thickening mechanism and polymer structures. Comprehensive skin
      sensory studies were carried out to test factors such as the pick-up, rub-in, and
      after-feel of these emulsions and the control sample. Results showed that all the
      samples demonstrated a non-Newtonian and shear-thinning behavior, and synthetic
      polymer-based formulas were more viscous than cellulose derivative-based ones.
      All eight attributes for the factors of appearance, pick-up, and rub-in showed
      statistically significant differences (p <= 0.05), whereas all five attributes
      for the after-feel factor exhibited no statistically significant differences (p >
      0.05) for different thickening agents. According to the results calculated using
      Pearson's correlation coefficients, four sensory attributes were mostly
      correlated with the rheological parameters.

PMID- 29658880
TI  - Crystal structure of intraflagellar transport protein 80 reveals a homo-dimer
      required for ciliogenesis.
AB  - Oligomeric assemblies of intraflagellar transport (IFT) particles build cilia
      through sequential recruitment and transport of ciliary cargo proteins within
      cilia. Here we present the 1.8 A resolution crystal structure of the
      Chlamydomonas IFT-B protein IFT80, which reveals the architecture of two N
      terminal beta-propellers followed by an alpha-helical extension. The N-terminal
      beta-propeller tethers IFT80 to the IFT-B complex via IFT38 whereas the second
      beta-propeller and the C-terminal alpha-helical extension result in IFT80 homo
      dimerization. Using CRISPR/Cas to create biallelic Ift80 frameshift mutations in
      IMCD3 mouse cells, we demonstrate that IFT80 is absolutely required for
      ciliogenesis. Structural mapping and rescue experiments reveal that human disease
      causing missense mutations do not cluster within IFT80 and form functional IFT
      particles. Unlike missense mutant forms of IFT80, deletion of the C-terminal
      dimerization domain prevented rescue of ciliogenesis. Taken together our results
      may provide a first insight into higher order IFT complex formation likely
      required for IFT train formation.

PMID- 29658881
TI  - Negative regulation of G2-M by ATR (mei-41)/Chk1(Grapes) facilitates tracheoblast
      growth and tracheal hypertrophy in Drosophila.
AB  - Imaginal progenitors in Drosophila are known to arrest in G2 during larval stages
      and proliferate thereafter. Here we investigate the mechanism and implications of
      G2 arrest in progenitors of the adult thoracic tracheal epithelium
      (tracheoblasts). We report that tracheoblasts pause in G2 for ~48-56 h and grow
      in size over this period. Surprisingly, tracheoblasts arrested in G2 express
      drivers of G2-M like Cdc25/String (Stg). We find that mechanisms that prevent G2
      M are also in place in this interval. Tracheoblasts activate Checkpoint Kinase
      1/Grapes (Chk1/Grp) in an ATR/mei-41-dependent manner. Loss of ATR/Chk1 led to
      precocious mitotic entry ~24-32 h earlier. These divisions were apparently normal
      as there was no evidence of increased DNA damage or cell death. However,
      induction of precocious mitoses impaired growth of tracheoblasts and the tracheae
      they comprise. We propose that ATR/Chk1 negatively regulate G2-M in developing
      tracheoblasts and that G2 arrest facilitates cellular and hypertrophic organ
      growth.

PMID- 29658883
TI  - A question of time.
AB  - How does a scientist balance establishing a career and starting a family?

PMID- 29658884
TI  - Modal analysis of the thermal conductivity of nanowires: examining unique thermal
      transport features.
AB  - In this study, unique thermal transport features of nanowires over bulk materials
      are investigated using a combined analysis based on lattice dynamics and
      equilibrium molecular dynamics (EMD). The evaluation of the thermal conductivity
      (TC) of Lenard-Jones nanowires becomes feasible due to the multi-step normal mode
      decomposition (NMD) procedure implemented in the study. A convergence issue of
      the TC of nanowires is addressed by the NMD implementation for two case studies,
      which employ pristine nanowires (PNW) and superlattice nanowires. Interestingly,
      mode relaxation times at low frequencies of acoustic branches exhibit signs of
      approaching constant values, thus indicating the convergence of TC. The TC
      evaluation procedure is further verified by implementing EMD-based Green-Kubo
      analysis, which is based on a fundamentally different physical perspective.
      Having verified the NMD procedure, the non-monotonic trend of the TC of nanowires
      is addressed. It is shown that the principal cause for the observed trend is due
      to the competing effects of long wavelength phonons and phonon-surface
      scatterings as the nanowire's cross-sectional width is changed. A computational
      procedure is developed to decompose the different modal contribution to the TC of
      shell alloy nanowires (SANWs) using virtual crystal NMD and the Allen-Feldman
      theory. Several important conclusions can be drawn from the results. A propagons
      to non-propagons boundary appeared, resulting in a cut-off frequency (omega cut);
      moreover, as alloy atomic mass is increased, omega cut shifts to lower
      frequencies. The existence of non-propagons partly causes the low TC of SANWs. It
      can be seen that modes with low frequencies demonstrate a similar behavior to
      corresponding modes of PNWs. Moreover, lower group velocities associated with
      higher alloy atomic mass resulted in a lower TC of SANWs.

PMID- 29658882
TI  - Transcriptomic analyses reveal rhythmic and CLOCK-driven pathways in human
      skeletal muscle.
AB  - Circadian regulation of transcriptional processes has a broad impact on cell
      metabolism. Here, we compared the diurnal transcriptome of human skeletal muscle
      conducted on serial muscle biopsies in vivo with profiles of human skeletal
      myotubes synchronized in vitro. More extensive rhythmic transcription was
      observed in human skeletal muscle compared to in vitro cell culture as a large
      part of the in vivo mRNA rhythmicity was lost in vitro. siRNA-mediated clock
      disruption in primary myotubes significantly affected the expression of ~8% of
      all genes, with impact on glucose homeostasis and lipid metabolism. Genes
      involved in GLUT4 expression, translocation and recycling were negatively
      affected, whereas lipid metabolic genes were altered to promote activation of
      lipid utilization. Moreover, basal and insulin-stimulated glucose uptake were
      significantly reduced upon CLOCK depletion. Our findings suggest an essential
      role for the circadian coordination of skeletal muscle glucose homeostasis and
      lipid metabolism in humans.

PMID- 29658885
TI  - A CE-FL based method for real-time detection of in-capillary self-assembly of the
      nanoconjugates of polycysteine ligand and quantum dots.
AB  - Small molecules with free thiol groups always show high binding affinity to
      quantum dots (QDs). However, it is still highly challenging to detect the binding
      capacity between thiol-containing molecules and QDs inside a capillary. To
      conquer this limitation, a capillary electrophoresis with fluorescence detection
      (CE-FL) based assay was proposed and established to investigate the binding
      capacity between QDs and a poly-thiolated peptide (ATTO 590-DDSSGGCCPGCC, ATTO
      C4). Interestingly, the results showed that interval time had a great influence
      on QDs and ATTO-C4 self-assembly, which can be attributed to longer interval time
      benefitting the binding of QDs to ATTO-C4. The stability assays on ATTO-C4-QD
      assembly indicated that high concentration of imidazole or GSH had a high
      capability of competing with the bound ATTO-C4, evidenced by dramatically
      dropping of S 625/S 565 ratio from 0.78 to 0.30 or 0.29. Therefore, all these
      results above suggested that this novel CE-FL based detection assay could be
      successfully applied to the binding studies between QDs and thiol-containing
      biomolecules.

PMID- 29658886
TI  - Swelling kinetics and electrical charge transport in PEDOT:PSS thin films exposed
      to water vapor.
AB  - We report the swelling kinetics and evolution of the electrical charge transport
      in poly(3,4-ethylene dioxythiophene) polystyrene sulfonate (PEDOT:PSS) thin films
      subjected to water vapor. Polymer films swell by the diffusion of water vapor and
      are found to undergo structural relaxations. Upon exposure to water vapor,
      primarily the hygroscopic PSS shell, which surrounds the conducting PEDOT-rich
      cores, takes up water vapor and subsequently swells. We found that the degree of
      swelling largely depends on the PEDOT to PSS ratio. Swelling driven microscopic
      rearrangement of the conducting PEDOT-rich cores in the PSS matrix strongly
      influences the electrical charge transport of the polymer film. Swelling induced
      increase as well as decrease of electrical resistance are observed in polymer
      films having different PEDOT to PSS ratio. This anomalous charge transport
      behavior in PEDOT:PSS films is reconciled by taking into account the contrasting
      swelling behavior of the PSS and the conducting PEDOT-rich cores leading to
      spatial segregation of PSS in films with PSS as a minority phase and by a net
      increase in mean separation between conducting PEDOT-rich cores for films having
      abundance of PSS.

PMID- 29658887
TI  - Two-qubit logical operations in three quantum dots system.
AB  - We consider a model of two interacting always-on, exchange-only qubits for which
      controlled phase (CPHASE), controlled NOT (CNOT), quantum Fourier transform (QFT)
      and SWAP operations can be implemented only in a few electrical pulses in a
      nanosecond time scale. Each qubit is built of three quantum dots (TQD) in a
      triangular geometry with three electron spins which are always kept coupled by
      exchange interactions only. The qubit states are encoded in a doublet subspace
      and are fully electrically controlled by a voltage applied to gate electrodes.
      The two qubit quantum gates are realized by short electrical pulses which change
      the triangular symmetry of TQD and switch on exchange interaction between the
      qubits. We found an optimal configuration to implement the CPHASE gate by a
      single pulse of the order 2.3 ns. Using this gate, in combination with single
      qubit operations, we searched for optimal conditions to perform the other gates:
      CNOT, QFT and SWAP. Our studies take into account environment effects and leakage
      processes as well. The results suggest that the system can be implemented for
      fault tolerant quantum computations.

PMID- 29658888
TI  - Estimation of degree of polymerization of poly-acrylonitrile-grafted carbon
      nanotubes using Guinier plot of small angle x-ray scattering.
AB  - Small angle x-ray scattering (SAXS) was used to estimate the degree of
      polymerization of polymer-grafted carbon nanotubes (CNTs) synthesized using a
      'grafting from' method. This analysis characterizes the grafted polymer chains
      without cleaving them from CNTs, and provides reliable data that can complement
      conventional methods such as thermogravimetric analysis or transmittance electron
      microscopy. Acrylonitrile was polymerized from the surface of the CNTs by using
      redox initiation to produce poly-acrylonitrile-grafted CNTs (PAN-CNTs).
      Polymerization time and the initiation rate were varied to control the degree of
      polymerization. Radius of gyration (R g ) of PAN-CNTs was determined using the
      Guinier plot obtained from SAXS solution analysis. The results showed consistent
      values according to the polymerization condition, up to a maximum R g  = 125.70 A
      whereas that of pristine CNTs was 99.23 A. The dispersibility of PAN-CNTs in N,N
      dimethylformamide was tested using ultraviolet-visible-near infrared spectroscopy
      and was confirmed to increase as the degree of polymerization increased. This
      analysis will be helpful to estimate the degree of polymerization of any polymer
      grafted CNTs synthesized using the 'grafting from' method and to fabricate
      polymer/CNT composite materials.

PMID- 29658889
TI  - Cross-correlation analysis of pulse wave propagation in arteries: in vitro
      validation and in vivo feasibility.
AB  - The stiffness of the arteries is known to be an indicator of the progression of
      various cardiovascular diseases. Clinically, the pulse wave velocity (PWV) is
      used as a surrogate for arterial stiffness. Pulse wave imaging (PWI) is a non
      invasive, ultrasound-based imaging technique capable of mapping the motion of the
      vessel walls, allowing the local assessment of arterial properties.
      Conventionally, a distinctive feature of the displacement wave (e.g. the 50%
      upstroke) is tracked across the map to estimate the PWV. However, the presence of
      reflections, such as those generated at the carotid bifurcation, can bias the PWV
      estimation. In this paper, we propose a two-step cross-correlation based method
      to characterize arteries using the information available in the PWI spatio
      temporal map. First, the area under the cross-correlation curve is proposed as an
      index for locating the regions of different properties. Second, a local peak of
      the cross-correlation function is tracked to obtain a less biased estimate of the
      PWV. Three series of experiments were conducted in phantoms to evaluate the
      capabilities of the proposed method compared with the conventional method. In the
      ideal case of a homogeneous phantom, the two methods performed similarly and
      correctly estimated the PWV. In the presence of reflections, the proposed method
      provided a more accurate estimate than conventional processing: e.g. for the soft
      phantom, biases of  -0.27 and -0.71 m . s-1 were observed. In a third series of
      experiments, the correlation-based method was able to locate two regions of
      different properties with an error smaller than 1 mm. It also provided more
      accurate PWV estimates than conventional processing (biases:  -0.12 versus -0.26
      m . s-1). Finally, the in vivo feasibility of the proposed method was
      demonstrated in eleven healthy subjects. The results indicate that the
      correlation-based method might be less precise in vivo but more accurate than the
      conventional method.

PMID- 29658890
TI  - Optical absorption by indirect excitons in a transition metal
      dichalcogenide/hexagonal boron nitride heterostructure.
AB  - We study optical transitions in spatially indirect excitons in transition metal
      dichalcogenide (TMDC) heterostructures separated by an integer number of
      hexagonal boron nitride (h-BN) monolayers. By solving the Schrodinger equation
      with the Keldysh potential for a spatially indirect exciton, we obtain
      eigenfunctions and eigenenergies for the ground and excited states and study
      their dependence on the interlayer separation, controlled by varying the number
      of h-BN monolayers. The oscillator strength, optical absorption coefficient, and
      optical absorption factor, the fraction of incoming photons absorbed in the
      TMDC/h-BN/TMDC heterostructure, are evaluated and studied as a function of the
      interlayer separation. Using input parameters from the existing literature which
      give the largest and the smallest spatially indirect exciton binding energy, we
      provide upper and lower bounds on all quantities presented.

PMID- 29658891
TI  - Dynamic mechanical control of local vacancies in NiO thin films.
AB  - The manipulation of local ionic behavior via external stimuli in oxide systems is
      of great interest because it can help in directly tuning material properties.
      Among external stimuli, mechanical force has attracted intriguing attention as
      novel stimulus for ionic modulation. Even though effectiveness of mechanical
      force on local ionic modulation has been validated in terms of static effect, its
      real-time i.e., dynamic, behavior under an application of the force is barely
      investigated in spite of its crucial impact on device performance such as force
      or pressure sensors. In this study, we explore dynamic ionic behavior modulated
      by mechanical force in NiO thin films using electrochemical strain microscopy
      (ESM). Ionically mediated ESM hysteresis loops were significantly varied under an
      application of mechanical force. Based on these results, we were able to
      investigate relative relationship between the force and voltage effects on ionic
      motion and, further, control effectively ionic behavior through combination of
      mechanical and electrical stimuli. Our results can provide comprehensive
      information on the effect of mechanical forces on ionic dynamics in ionic
      systems.

PMID- 29658892
TI  - Compact DD generator-based in vivo neutron activation analysis (IVNAA) system to
      determine sodium concentrations in human bone.
AB  - OBJECTIVE: This study presents the development of a noninvasive method for
      monitoring Na in human bone. Many diseases, such as hypertension and
      osteoporosis, are closely associated with sodium (Na) retention in the human
      body. Na retention is generally evaluated by calculating the difference between
      dietary intake and excretion. There is currently no method to directly quantify
      Na retained in the body. Bone is a storage for many elements, including Na, which
      renders bone Na an ideal biomarker to study Na metabolism and retention.
      APPROACH: A customized compact deuterium-deuterium (DD) neutron generator was
      used to produce neutrons for in vivo neutron activation analysis (IVNAA), with a
      moderator/reflector/shielding assembly optimized for human hand irradiation in
      order to maximize the thermal neutron flux inside the irradiation cave and to
      limit radiation exposure to the hand and the whole body. MAIN RESULTS: The
      experimental results show that the system is able to detect sodium levels in the
      bone as low as 16 ug Na g-1 dry bone with an effective dose to the body of about
      27 uSv. The simulation results agree with the numbers estimated from the
      experiment. SIGNIFICANCE: This is expected to be a feasible method for measuring
      the change of Na in bone. The low detection limit indicates this will be a useful
      system to study the association between Na retention and related diseases.

PMID- 29658893
TI  - Role of zero-point effects in stabilizing the ground state structure of bulk
      Fe2P.
AB  - Structural stability of Fe2P is investigated in detail using first-principles
      calculations based on density functional theory. While the orthorhombic C23 phase
      is found to be energetically more stable, the experiments suggest it to be
      hexagonal C22 phase. In the present study, we show that in order to obtain the
      correct ground state structure of Fe2P from the first-principles based methods it
      is utmost necessary to consider the zero-point effects such as zero-point
      vibrations and spin fluctuations. This study demonstrates an exceptional case
      where a bulk material is stabilized by quantum effects, which are usually
      important in low-dimensional materials. Our results also indicate the possibility
      of magnetic field induced structural quantum phase transition in Fe2P, which
      should form the basis for further theoretical and experimental efforts.

PMID- 29658895
TI  - Observation of surface plasmon polaritons in 2D electron gas of surface electron
      accumulation in InN nanostructures.
AB  - Recently, heavily doped semiconductors have been emerging as an alternative to
      low-loss plasmonic materials. InN, belonging to the group III nitrides, possesses
      the unique property of surface electron accumulation (SEA), which provides a 2D
      electron gas (2DEG) system. In this report, we demonstrated the surface plasmon
      properties of InN nanoparticles originating from SEA using the real-space mapping
      of the surface plasmon fields for the first time. The SEA is confirmed by Raman
      studies, which are further corroborated by photoluminescence and photoemission
      spectroscopic studies. The frequency of 2DEG corresponding to SEA is found to be
      in the THz region. The periodic fringes are observed in the near-field scanning
      optical microscopic images of InN nanostructures. The observed fringes are
      attributed to the interference of propagated and back-reflected surface plasmon
      polaritons (SPPs). The observation of SPPs is solely attributed to the 2DEG
      corresponding to the SEA of InN. In addition, a resonance kind of behavior with
      the enhancement of the near-field intensity is observed in the near-field images
      of InN nanostructures. Observation of SPPs indicates that InN with SEA can be a
      promising THz plasmonic material for light confinement.

PMID- 29658894
TI  - Assessing mental stress from the photoplethysmogram: a numerical study.
AB  - OBJECTIVE: Mental stress is detrimental to cardiovascular health, being a risk
      factor for coronary heart disease and a trigger for cardiac events. However, it
      is not currently routinely assessed. The aim of this study was to identify
      features of the photoplethysmogram (PPG) pulse wave which are indicative of
      mental stress. APPROACH: A numerical model of pulse wave propagation was used to
      simulate blood pressure signals, from which simulated PPG pulse waves were
      estimated using a transfer function. Pulse waves were simulated at six levels of
      stress by changing the model input parameters both simultaneously and
      individually, in accordance with haemodynamic changes associated with stress.
      Thirty-two feature measurements were extracted from pulse waves at three
      measurement sites: the brachial, radial and temporal arteries. Features which
      changed significantly with stress were identified using the Mann-Kendall
      monotonic trend test. MAIN RESULTS: Seventeen features exhibited significant
      trends with stress in measurements from at least one site. Three features showed
      significant trends at all three sites: the time from pulse onset to peak, the
      time from the dicrotic notch to pulse end, and the pulse rate. More features
      showed significant trends at the radial artery (15) than the brachial (8) or
      temporal (7) arteries. Most features were influenced by multiple input
      parameters. SIGNIFICANCE: The features identified in this study could be used to
      monitor stress in healthcare and consumer devices. Measurements at the radial
      artery may provide superior performance than the brachial or temporal arteries.
      In vivo studies are required to confirm these observations.

PMID- 29658897
TI  - Estimating and reporting error rates, and detecting improvements.

PMID- 29658896
TI  - Safety and quality of procedural sedation and analgesia practice for adult
      patients throughout Europe: A step forward.

PMID- 29658898
TI  - Reply to: estimating and reporting rates, and detecting improvements.

PMID- 29658899
TI  - Alveolar recruitment manoeuvres after cardiac surgery.

PMID- 29658900
TI  - Reply to: alveolar recruitment manoeuvres after cardiac surgery.

PMID- 29658901
TI  - Predictive models for acute kidney injury after cardiac surgery.

PMID- 29658902
TI  - Reply to: predictive models for acute kidney injury after cardiac surgery.

PMID- 29658903
TI  - High versus low PEEP for abdominal surgery.

PMID- 29658904
TI  - Reply to: high versus low positive end-expiratory pressure for abdominal surgery.

PMID- 29658905
TI  - Aprotinin and coronary artery bypass surgery.

PMID- 29658906
TI  - Reply to: aprotinin and coronary artery bypass surgery.

PMID- 29658907
TI  - Dobutamine and its haemodynamic effects in pleural effusion.

PMID- 29658908
TI  - Reply to: dobutamine and its haemodynamic effects in pleural effusion.

PMID- 29658909
TI  - Pretreatment With Argon Protects Human Cardiac Myocyte-Like Progenitor Cells from
      Oxygen Glucose Deprivation-Induced Cell Death by Activation of AKT and
      Differential Regulation of Mapkinases.
AB  - BACKGROUND: The noble gas argon induces cardioprotection in a rabbit model of
      myocardial ischemia and reperfusion. However, no studies in human primary cells
      or subjects have been performed so far. We used human cardiac myocyte-like
      progenitor cells (HCMs) to investigate the protective effect on the cellular
      level. METHODS: HCMs were pretreated with 30% or 50% argon before oxygen-glucose
      deprivation (OGD) and reperfusion. We evaluated apoptotic states by flow
      cytometry and the activation of mitogen-activated protein kinase (MAPKs) members
      extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK), p38
      MAPkinase, and protein kinase B (Akt) by Westernblot analysis and by activity
      assays of downstream transcription factors. Specific inhibitors were used to
      proof a significant participation of these pathways in the protection by argon.
      Beneficial effects were further assessed by TdT-mediated dUTP-biotin nick end
      labeling (TUNEL) assay, lactate dehydrogenase (LDH), mitochondrial
      deoxyribonucleic acid (mtDNA), and cytokine release. RESULTS: Pretreatment with
      30% or 50% argon for 90 min before OGD resulted in a significant protection of
      HCMs against apoptosis. This effect was reversed by the application of MAPK and
      Akt inhibitors during argon exposure. Argon 30% reduced the release of LDH by 33%
      and mtDNA by 45%. The release of interleukin 1beta was reduced by 44% after OGD
      and more than 90% during reperfusion. CONCLUSIONS: Pretreatment with argon
      protects HCMs from apoptosis under ischemic conditions via activation of Akt,
      Erk, and biphasic regulation of JNK. Argon gas is cheap and easily administrable,
      and might be a novel therapy to reduce myocardial ischemia-reperfusion injury.

PMID- 29658910
TI  - Metabolic Syndrome, Anxiety and Depression in a Sample of Italian Primary Care
      Patients.
AB  - This cross-sectional study aimed at measuring the correlation and association of
      anxiety, depression and comorbid anxiety-depression symptoms with metabolic
      syndrome (MetS) in a sample of Italian primary care patients who attended their
      General Practitioner clinics over a 1-month period in 2013. The Hospital Anxiety
      and Depression Scale (HADS) was used to assess anxiety and depressive symptoms.
      The sample was made up of 129 patients (57% women; mean age, 61 +/- 12 years).
      The prevalence of MetS varied from 40% (Adult Treatment Panel III-Revised
      criteria) to 48% (International Diabetes Federation criteria). The prevalence of
      symptoms of anxiety, depression and comorbid anxiety and depression was,
      respectively, 26%, 2%, and 15%. MetS (defined according to Adult Treatment Panel
      III-Revised criteria) was associated with comorbid anxiety-depressive symptoms
      (odds ratio [OR] = 3.84, 95% confidence interval [CI] = 1.26-11.71), but not with
      anxiety or depressive symptoms only. Out of the individual components of MetS,
      enlarged waist circumference was associated with anxiety symptoms (OR = 4.22, 95%
      CI = 1.56-11.44).

PMID- 29658911
TI  - Concern about US Preventive Services Task Force recommendation on hormone therapy
      for the primary prevention of chronic conditions in postmenopausal women.

PMID- 29658912
TI  - Hysterectomy with ovarian conservation: is there a downside?

PMID- 29658913
TI  - Visualization of Thalamocortical Axon Branching and Synapse Formation in
      Organotypic Cocultures.
AB  - Axon branching and synapse formation are crucial processes for establishing
      precise neuronal circuits. During development, sensory thalamocortical (TC) axons
      form branches and synapses in specific layers of the cerebral cortex. Despite the
      obvious spatial correlation between axon branching and synapse formation, the
      causal relationship between them is poorly understood. To address this issue, we
      recently developed a method for simultaneous imaging of branching and synapse
      formation of individual TC axons in organotypic cocultures. This protocol
      describes a method which consists of a combination of an organotypic coculture
      and electroporation. Organotypic cocultures of the thalamus and cerebral cortex
      facilitate gene manipulation and observation of axonal processes, preserving
      characteristic structures such as laminar configuration. Two distinct plasmids
      encoding DsRed and EGFP-tagged synaptophysin (SYP-EGFP) were co-transfected into
      a small number of thalamic neurons by an electroporation technique. This method
      allowed us to visualize individual axonal morphologies of TC neurons and their
      presynaptic sites simultaneously. The method also enabled long-term observation
      which revealed the causal relationship between axon branching and synapse
      formation.

PMID- 29658914
TI  - Visualization and Quantification of Mesenchymal Cell Adipogenic Differentiation
      Potential with a Lineage Specific Marker.
AB  - Several dyes are currently available for use in detecting differentiation of
      mesenchymal cells into adipocytes. Dyes, such as Oil Red O, are cheap, easy to
      use and widely utilized by laboratories analyzing the adipogenic potential of
      mesenchymal cells. However, they are not specific to changes in gene
      transcription. We have developed a gene-specific differentiation assay to analyze
      when a mesenchymal cell has switched its fate to an adipogenic lineage. Immuno
      labelling against fatty acid binding protein-4 (FABP4), a lineage-specific marker
      of adipogenic differentiation, enabled visualization and quantification of
      differentiated cells. The ability to quantify adipogenic differentiation
      potential of mesenchymal cells in a 96 well microplate format has promising
      implications for a number of applications. Hundreds of clinical trials involve
      the use of adult mesenchymal stromal cells and it is currently difficult to
      correlate therapeutic outcomes within and especially between such clinical
      trials. This simple high-throughput FABP4 assay provides a quantitative assay for
      assessing the differentiation potential of patient-derived cells and is a robust
      tool for comparing different isolation and expansion methods. This is
      particularly important given the increasing recognition of the heterogeneity of
      the cells being administered to patients in mesenchymal cell products. The assay
      also has potential utility in high throughput drug screening, particularly in
      obesity and pre-diabetes research.

PMID- 29658915
TI  - Adapting 3' Rapid Amplification of CDNA Ends to Map Transcripts in Cancer.
AB  - Maturation of eukaryotic mRNAs involves 3' end formation, which involves the
      addition of a poly(A) tail. In order to map the 3' end of a gene, the traditional
      method of choice is 3' rapid amplification of cDNA ends (3' RACE). Protocols for
      3' RACE require the careful design and selection of nested primers within the 3'
      untranslated region (3' UTR) of the target gene of interest. However, with a few
      modifications the protocol can be used to include the entire 3' UTR and sequences
      within the open reading frame (ORF), providing a more comprehensive picture of
      the relationship between the ORF and the 3' UTR. This is in addition to
      identification of the polyadenylation signal (PAS), as well as the cleavage and
      polyadenylation site provided by conventional 3' RACE. Expanded 3' RACE can
      detect unusual 3' UTRs, including gene fusions within the 3' UTR, and the
      sequence information can be used to predict potential miRNA binding sites as well
      as AU rich destabilizing elements that may affect the stability of the
      transcript.

PMID- 29658916
TI  - Microdissection of Primary Renal Tissue Segments and Incorporation with Novel
      Scaffold-free Construct Technology.
AB  - Kidney transplantation is now a mainstream therapy for end-stage renal disease.
      However, with approximately 96,000 people on the waiting list and only one-fourth
      of these patients achieving transplantation, there is a dire need for
      alternatives for those with failing organs. In order to decrease the harmful
      consequences of dialysis along with the overall healthcare costs it incurs,
      active investigation is ongoing in search of alternative solutions to organ
      transplantation. Implantable tissue-engineered renal cellular constructs are one
      such feasible approach to replacing lost renal functionality. Here, described for
      the first time, is the microdissection of murine kidneys for isolation of living
      corticomedullary renal segments. These segments are capable of rapid
      incorporation within scaffold-free endothelial-fibroblast constructs which may
      enable rapid connection with host vasculature once implanted. Adult mouse kidneys
      were procured from living donors, followed by stereoscope microdissection to
      obtain renal segments 200 - 300 um in diameter. Multiple renal constructs were
      fabricated using primary renal segments harvested from only one kidney. This
      method demonstrates a procedure which could salvage functional renal tissue from
      organs that would otherwise be discarded.

PMID- 29658917
TI  - Chemical Synthesis of Porous Barium Titanate Thin Film and Thermal Stabilization
      of Ferroelectric Phase by Porosity-Induced Strain.
AB  - Barium titanate (BaTiO3, hereafter BT) is an established ferroelectric material
      first discovered in the 1940s and still widely used because of its well-balanced
      ferroelectricity, piezoelectricity, and dielectric constant. In addition, BT does
      not contain any toxic elements. Therefore, it is considered to be an eco-friendly
      material, which has attracted considerable interest as a replacement for lead
      zirconate titanate (PZT). However, bulk BT loses its ferroelectricity at
      approximately 130  degrees C, thus, it cannot be used at high temperatures.
      Because of the growing demand for high-temperature ferroelectric materials, it is
      important to enhance the thermal stability of ferroelectricity in BT. In previous
      studies, strain originating from the lattice mismatch at hetero-interfaces has
      been used. However, the sample preparation in this approach requires complicated
      and expensive physical processes, which are undesirable for practical
      applications. In this study, we propose a chemical synthesis of a porous material
      as an alternative means of introducing strain. We synthesized a porous BT thin
      film using a surfactant-assisted sol-gel method, in which self-assembled
      amphipathic surfactant micelles were used as an organic template. Through a
      series of studies, we clarified that the introduction of pores had a similar
      effect on distorting the BT crystal lattice, to that of a hetero-interface,
      leading to the enhancement and stabilization of ferroelectricity. Owing to its
      simplicity and cost effectiveness, this fabrication process has considerable
      advantages over conventional methods.

PMID- 29658918
TI  - Whole-mount Confocal Microscopy for Adult Ear Skin: A Model System to Study Neuro
      vascular Branching Morphogenesis and Immune Cell Distribution.
AB  - Here, we present a protocol of a whole-mount adult ear skin imaging technique to
      study comprehensive three-dimensional neuro-vascular branching morphogenesis and
      patterning, as well as immune cell distribution at a cellular level. The analysis
      of peripheral nerve and blood vessel anatomical structures in adult tissues
      provides some insights into the understanding of functional neuro-vascular wiring
      and neuro-vascular degeneration in pathological conditions such as wound healing.
      As a highly informative model system, we have focused our studies on adult ear
      skin, which is readily accessible for dissection. Our simple and reproducible
      protocol provides an accurate depiction of the cellular components in the entire
      skin, such as peripheral nerves (sensory axons, sympathetic axons, and Schwann
      cells), blood vessels (endothelial cells and vascular smooth muscle cells), and
      inflammatory cells. We believe this protocol will pave the way to investigate
      morphological abnormalities in peripheral nerves and blood vessels as well as the
      inflammation in the adult ear skin under different pathological conditions.

PMID- 29658920
TI  - Identification of Dopamine D1-Alpha Receptor Within Rodent Nucleus Accumbens by
      an Innovative RNA In Situ Detection Technology.
AB  - In the central nervous system, the D1-alpha subtype receptor (Drd1alpha) is the
      most abundant dopamine (DA) receptor, which plays a vital role in regulating
      neuronal growth and development. However, the mechanisms underlying Drd1alpha
      receptor abnormalities mediating behavioral responses and modulating working
      memory function are still unclear. Using a novel RNA in situ hybridization assay,
      the current study identified dopamine Drd1alpha receptor and tyrosine hydroxylase
      (TH) RNA expression from DA-related circuitry in the nucleus accumbens (NAc) area
      and substantia nigra region (SNR), respectively. Drd1alpha expression in the NAc
      shows a "discrete dot" staining pattern. Clear sex differences in Drd1alpha
      expression were observed. In contrast, TH shows a "clustered" staining pattern.
      Regarding TH expression, female rats displayed a higher signal expression per
      cell relative to male animals. The methods presented here provide a novel in situ
      hybridization technique for investigating changes in dopamine system dysfunction
      during the progression of central nervous system diseases.

PMID- 29658919
TI  - Generating Transgenic Plants with Single-copy Insertions Using BIBAC-GW Binary
      Vector.
AB  - When generating transgenic plants, generally the objective is to have stable
      expression of a transgene. This requires a single, intact integration of the
      transgene, as multi-copy integrations are often subjected to gene silencing. The
      Gateway-compatible binary vector based on bacterial artificial chromosomes
      (pBIBAC-GW), like other pBIBAC derivatives, allows the insertion of single-copy
      transgenes with high efficiency. As an improvement to the original pBIBAC, a
      Gateway cassette has been cloned into pBIBAC-GW, so that the sequences of
      interest can now be easily incorporated into the vector transfer DNA (T-DNA) by
      Gateway cloning. Commonly, the transformation with pBIBAC-GW results in an
      efficiency of 0.2-0.5%, whereby half of the transgenics carry an intact single
      copy integration of the T-DNA. The pBIBAC-GW vectors are available with
      resistance to Glufosinate-ammonium or DsRed fluorescence in seed coats for
      selection in plants, and with resistance to kanamycin as a selection in bacteria.
      Here, a series of protocols is presented that guide the reader through the
      process of generating transgenic plants using pBIBAC-GW: starting from
      recombining the sequences of interest into the pBIBAC-GW vector of choice, to
      plant transformation with Agrobacterium, selection of the transgenics, and
      testing the plants for intactness and copy number of the inserts using DNA
      blotting. Attention is given to designing a DNA blotting strategy to recognize
      single- and multi-copy integrations at single and multiple loci.

PMID- 29658921
TI  - Site-Directed Immobilization of Bone Morphogenetic Protein 2 to Solid Surfaces by
      Click Chemistry.
AB  - Different therapeutic strategies for the treatment of non-healing long bone
      defects have been intensively investigated. Currently used treatments present
      several limitations that have led to the use of biomaterials in combination with
      osteogenic growth factors, such as bone morphogenetic proteins (BMPs). Commonly
      used absorption or encapsulation methods require supra-physiological amounts of
      BMP2, typically resulting in a so-called initial burst release effect that
      provokes several severe adverse side effects. A possible strategy to overcome
      these problems would be to covalently couple the protein to the scaffold.
      Moreover, coupling should be performed in a site-specific manner in order to
      guarantee a reproducible product outcome. Therefore, we created a BMP2 variant,
      in which an artificial amino acid (propargyl-L-lysine) was introduced into the
      mature part of the BMP2 protein by codon usage expansion (BMP2-K3Plk). BMP2-K3Plk
      was coupled to functionalized beads through copper catalyzed azide-alkyne
      cycloaddition (CuAAC). The biological activity of the coupled BMP2-K3Plk was
      proven in vitro and the osteogenic activity of the BMP2-K3Plk-functionalized
      beads was proven in cell based assays. The functionalized beads in contact with
      C2C12 cells were able to induce alkaline phosphatase (ALP) expression in locally
      restricted proximity of the bead. Thus, by this technique, functionalized
      scaffolds can be produced that can trigger cell differentiation towards an
      osteogenic lineage. Additionally, lower BMP2 doses are sufficient due to the
      controlled orientation of site-directed coupled BMP2. With this method, BMPs are
      always exposed to their receptors on the cell surface in the appropriate
      orientation, which is not the case if the factors are coupled via non-site
      directed coupling techniques. The product outcome is highly controllable and,
      thus, results in materials with homogeneous properties, improving their
      applicability for the repair of critical size bone defects.

PMID- 29658922
TI  - Three-dimensional Rendering and Analysis of Immunolabeled, Clarified Human
      Placental Villous Vascular Networks.
AB  - Nutrient and gas exchange between mother and fetus occurs at the interface of the
      maternal intervillous blood and the vast villous capillary network that makes up
      much of the parenchyma of the human placenta. The distal villous capillary
      network is the terminus of the fetal blood supply after several generations of
      branching of vessels extending out from the umbilical cord. This network has a
      contiguous cellular sheath, the syncytial trophoblast barrier layer, which
      prevents mixing of fetal blood and the maternal blood in which it is continuously
      bathed. Insults to the integrity of the placental capillary network, occurring in
      disorders such as maternal diabetes, hypertension and obesity, have consequences
      that present serious health risks for the fetus, infant, and adult. To better
      define the structural effects of these insults, a protocol was developed for this
      study that captures capillary network structure on the order of 1 - 2 mm3 wherein
      one can investigate its topological features in its full complexity. To
      accomplish this, clusters of terminal villi from placenta are dissected, and the
      trophoblast layer and the capillary endothelia are immunolabeled. These samples
      are then clarified with a new tissue clearing process which makes it possible to
      acquire confocal image stacks to z- depths of ~1 mm. The three-dimensional
      renderings of these stacks are then processed and analyzed to generate basic
      capillary network measures such as volume, number of capillary branches, and
      capillary branch end points, as validation of the suitability of this approach
      for capillary network characterization.

PMID- 29658923
TI  - Micro-dissection of Enamel Organ from Mandibular Incisor of Rats Exposed to
      Environmental Toxicants.
AB  - Enamel defects resulting from environmental conditions and ways of life are
      public health concerns because of their high prevalence. These defects result
      from altered activity of cells responsible for enamel synthesis named
      ameloblasts, which present in enamel organ. During amelogenesis, ameloblasts
      follow a specific and precise sequence of events of proliferation,
      differentiation, and death. A rat continually growing incisors is a suitable
      experimental model to study ameloblast activity and differentiation stages in
      physiological and pathological conditions. Here, we describe a reliable and
      consistent method to micro-dissect enamel organ of rats exposed to environmental
      toxicants. The micro-dissected dental epithelia contain secretion- and maturation
      stage ameloblasts that may be used for qualitative experiments, such as
      immunohistochemistry assays and in situ hybridization, as well as for
      quantitative analyses such as RT-qPCR, RNA-seq, and Western blotting.

PMID- 29658924
TI  - An Efficient and Simple Method to Establish NK and T Cell Lines from Patients
      with Chronic Active Epstein-Barr Virus Infection.
AB  - A number of methods have been described to establish NK/T cell lines from
      patients with lymphoma or lymphoproliferative syndrome. These methods employed
      feeder cells, purified NK or T cells with as much as 10 mL of blood, or a high
      dose of IL-2. This study presents a new method with a powerful and simple
      strategy to establish NK and T cell lines by culturing the peripheral blood
      mononuclear cells (PBMC) with the addition of recombinant human IL-2 (rhIL-2),
      and uses as little as 2 mL of whole blood. The cells can proliferate quickly in
      two weeks and be maintained for more than 3 months. With this method, 7 NK or T
      cell lines have been established with a high success rate. This method is simple,
      reliable, and applicable to establishing cell lines from more cases of CAEBV or
      NK/T cell lymphoma.

PMID- 29658925
TI  - Measuring Gene Expression in Bombarded Barley Aleurone Layers with Increased
      Throughput.
AB  - The aleurone layer of barley grains is an important model system for hormone
      regulated gene expression in plants. In aleurone cells, genes required for
      germination or early seedling development are activated by gibberellin (GA),
      while genes associated with stress responses are activated by abscisic acid
      (ABA). The mechanisms of GA and ABA signaling can be interrogated by introducing
      reporter gene constructs into aleurone cells via particle bombardment, with the
      resulting transient expression measured using enzyme assays. An improved protocol
      is reported that partially automates and streamlines the grain homogenization
      step and the enzyme assays, allowing significantly more throughput than existing
      methods. Homogenization of the grain samples is carried out using an automated
      tissue homogenizer, and GUS (beta-glucuronidase) assays are carried out using a
      96-well plate system. Representative results using the protocol suggest that
      phospholipase D activity may play an important role in the activation of HVA1
      gene expression by ABA, through the transcription factor TaABF1.

PMID- 29658927
TI  - Tumor Engraftment in a Xenograft Mouse Model of Human Mantle Cell Lymphoma.
AB  - B lymphocytes are key players in immune cell circulation and they mainly home to
      and reside in lymphoid organs. While normal B cells only proliferate when
      stimulated by T lymphocytes, oncogenic B cells survive and expand autonomously in
      undefined organ niches. Mantle cell lymphoma (MCL) is one such B cell disorder,
      where the median survival rate of patients is 4 - 5 years. This calls for the
      need of effective mechanisms by which the homing and engraftment of these cells
      are blocked in order to increase the survival and longevity of patients.
      Therefore, the effort to develop a xenograft mouse model to study the efficacy of
      MCL therapeutics by blocking the homing mechanism in vivo is of utmost
      importance. Development of animal recipients for human cell xenotransplantation
      to test early stage drugs have long been pursued, as relevant preclinical mouse
      models are crucial to screen new therapeutic agents. This animal model is
      developed to avoid human graft rejection and to establish a model for human
      diseases, and it may be an extremely useful tool to study disease progression of
      different lymphoma types and to perform preclinical testing of candidate drugs
      for hematologic malignancies, like MCL. We established a xenograft mouse model
      that will serve as an excellent resource to study and develop novel therapeutic
      approaches for MCL.

PMID- 29658926
TI  - Evaluation of Stem Cell Therapies in a Bilateral Patellar Tendon Injury Model in
      Rats.
AB  - Regenerative medicine provides novel alternatives to conditions that challenge
      traditional treatments. The prevalence and morbidity of tendinopathy across
      species, combined with the limited healing properties of this tissue, have
      prompted the search for cellular therapies and propelled the development of
      experimental models to study their efficacy. Umbilical cord matrix-derived
      mesenchymal stem cells (UCM-MSC) are appealing candidates because they are
      abundant, easy to collect, circumvent the ethical concerns and risk of teratoma
      formation, yet resemble primitive embryonic stem cells more closely than adult
      tissue-derived MSCs. Significant interest has focused on chitosan as a strategy
      to enhance the properties of MSCs through spheroid formation. This paper details
      techniques to isolate UCM-MSCs, prepare spheroids on chitosan film, and analyze
      the effect of spheroid formation on surface marker expression. Consequently,
      creation of a bilateral patellar tendon injury model in rats is described for in
      vivo implantation of UCM-MSC spheroids formed on chitosan film. No complication
      was observed in the study with respect to morbidity, stress rising effects, or
      tissue infection. The total functional score of the operated rats at 7 days was
      lower than that of normal rats, but returned to normal within 28 days after
      surgery. Histological scores of tissue-healing confirmed the presence of a clot
      in treated defects evaluated at 7 days, absence of foreign body reaction, and
      progressing healing at 28 days. This bilateral patella tendon defect model
      controls inter-individual variation via creation of an internal control in each
      rat, was associated with acceptable morbidity, and allowed detection of
      differences between untreated tendons and treatments.

PMID- 29658928
TI  - A Burrowing/Tunneling Assay for Detection of Hypoxia in Drosophila melanogaster
      Larvae.
AB  - Oxygen deprivation in animals can result from exposure to low atmospheric oxygen
      levels or from internal tissue damage that interferes with oxygen distribution.
      It is also possible that aberrant behavior of oxygen-sensing neurons could induce
      hypoxia-like behavior in the presence of normal oxygen levels. In D.
      melanogaster, development at low oxygen levels results in inhibition of growth
      and sluggish behavior during the larval phases. However, these established
      manifestations of oxygen deficit overlap considerably with the phenotypes of many
      mutations that regulate growth, stress responses or locomotion. As result, there
      is currently no assay available to identify i) cellular hypoxia induced by a
      mutation or ii) hypoxia-like behavior when induced by abnormal neuronal behavior.
      We have recently identified two distinctive behaviors in D. melanogaster larvae
      that occur at normal oxygen levels in response to internal detection of hypoxia.
      First, at all stages, such larvae avoid burrowing into food, often straying far
      away from a food source. Second, tunneling into a soft substratum, which normally
      occurs during the wandering third instar stage is completely abolished if larvae
      are hypoxic. The assay described here is designed to detect and quantitate these
      behaviors and thus to provide a way to detect hypoxia induced by internal damage
      rather than low external oxygen. Assay plates with an agar substratum and a
      central plug of yeast paste are used to support animals through larval life. The
      positions and state of the larvae are tracked daily as they proceed from first to
      third instar. The extent of tunneling into the agar substratum during wandering
      phase is quantitated after pupation using NIH ImageJ. The assay will be of value
      in determining when hypoxia is a component of a mutant phenotype and thus provide
      insight into possible sites of action of the gene in question.

PMID- 29658929
TI  - Partial Bile Duct Ligation in the Mouse: A Controlled Model of Localized
      Obstructive Cholestasis.
AB  - In rodents, complete bile duct ligation (cBDL) of the common bile duct is an
      established surgical technique for studying obstructive cholestasis and bile duct
      proliferation. However, long-term experiments can lead to increased morbidity and
      mortality. In select mouse strains with underlying liver disease, meaningful
      comparisons can be made even with ligation of a single lobe of the liver, which
      can reduce animal losses and expenses. Here, we describe partial bile duct
      ligation (pBDL) in the mouse, in which only the left hepatic bile duct is
      ligated, causing biliary obstruction in the left lobe but not the remaining
      lobes. With careful microsurgical technique, pBDL experiments can be cost
      effective, since the unligated lobe serves as an internal control to the ligated
      lobes, when subjected to the same conditions in the same animal. Unlike cBDL, a
      separate sham-operated control group is not necessary. pBDL is highly useful to
      directly compare localized versus systemic effects of cholestasis and other
      retained bile components. pBDL can also be repurposed as a novel method to
      investigate mechanisms related to medications and cell migration.

PMID- 29658930
TI  - Preparation and High-temperature Anti-adhesion Behavior of a Slippery Surface on
      Stainless Steel.
AB  - Anti-adhesion surfaces with high-temperature resistance have a wide application
      potential in electrosurgical instruments, engines, and pipelines. A typical anti
      wetting superhydrophobic surface easily fails when exposed to a high-temperature
      liquid. Recently, Nepenthes-inspired slippery surfaces demonstrated a new way to
      solve the adhesion problem. A lubricant layer on the slippery surface can act as
      a barrier between the repelled materials and the surface structure. However, the
      slippery surfaces in previous studies rarely showed high-temperature resistance.
      Here, we describe a protocol for the preparation of slippery surfaces with high
      temperature resistance. A photolithography-assisted method was used to fabricate
      pillar structures on stainless steel. By functionalizing the surface with saline,
      a slippery surface was prepared by adding silicone oil. The prepared slippery
      surface maintained the anti-wetting property for water, even when the surface was
      heated to 300  degrees C. Also, the slippery surface exhibited great anti
      adhesion effects on soft tissues at high temperatures. This type of slippery
      surface on stainless steel has applications in medical devices, mechanical
      equipment, etc.

PMID- 29658931
TI  - Optical Cross-Sectional Muscle Area Determination of Drosophila Melanogaster
      Adult Indirect Flight Muscles.
AB  - Muscle mass wasting, known as muscle atrophy, is a common phenotype in Drosophila
      models of neuromuscular diseases. We have used the indirect flight muscles (IFMs)
      of flies, specifically the dorso-longitudinal muscles (DLM), as the experimental
      subject to measure the atrophic phenotype brought about by different genetic
      causes. In this protocol, we describe how to embed fly thorax muscles for semi
      thin sectioning, how to obtain a good contrast between muscle and the surrounding
      tissue, and how to process optical microscope images for semiautomatic
      acquisition of quantifiable data and analysis. We describe three specific
      applications of the methodological pipeline. First, we show how the method can be
      applied to quantify muscle degeneration in a myotonic dystrophy fly model;
      second, measurement of muscle cross-sectional area can help to identify genes
      that either promote or prevent muscle atrophy and/or muscle degeneration; third,
      this protocol can be applied to determine whether a candidate compound is able to
      significantly modify a given atrophic phenotype induced by a disease-causing
      mutation or by an environmental trigger.

PMID- 29658932
TI  - In Situ High Pressure Hydrogen Tribological Testing of Common Polymer Materials
      Used in the Hydrogen Delivery Infrastructure.
AB  - High pressure hydrogen gas is known to adversely affect metallic components of
      compressors, valves, hoses, and actuators. However, relatively little is known
      about the effects of high pressure hydrogen on the polymer sealing and barrier
      materials also found within these components. More study is required in order to
      determine the compatibility of common polymer materials found in the components
      of the hydrogen fuel delivery infrastructure with high pressure hydrogen. As a
      result, it is important to consider the changes in physical properties such as
      friction and wear in situ while the polymer is exposed to high pressure hydrogen.
      In this protocol, we present a method for testing the friction and wear
      properties of ethylene propylene diene monomer (EPDM) elastomer samples in a 28
      MPa high pressure hydrogen environment using a custom-built in situ pin-on-flat
      linear reciprocating tribometer. Representative results from this testing are
      presented which indicate that the coefficient of friction between the EPDM sample
      coupon and steel counter surface is increased in high pressure hydrogen as
      compared to the coefficient of friction similarly measured in ambient air.

PMID- 29658933
TI  - Grafting Multiwalled Carbon Nanotubes with Polystyrene to Enable Self-Assembly
      and Anisotropic Patchiness.
AB  - We demonstrate a straightforward protocol to graft pristine multiwalled carbon
      nanotubes (MWCNTs) with polystyrene (PS) chains at the sidewalls through a free
      radical polymerization strategy to enable the modulation of the nanotube surface
      properties and produce supramolecular self-assembly of the nanostructures. First,
      a selective hydroxylation of the pristine nanotubes through a biphasic
      catalytically mediated oxidation reaction creates superficially distributed
      reactive sites at the sidewalls. The latter reactive sites are subsequently
      modified with methacrylic moieties using a silylated methacrylic precursor to
      create polymerizable sites. Those polymerizable groups can address further
      polymerization of styrene to produce a hybrid nanomaterial containing PS chains
      grafted to the nanotube sidewalls. The polymer-graft content, amount of silylated
      methacrylic moieties introduced and hydroxylation modification of the nanotubes
      are identified and quantified by Thermogravimetric Analysis (TGA). The presence
      of reactive functional groups hydroxyl and silylated methacrylate are confirmed
      by Fourier Transform Infrared Spectroscopy (FT-IR). Polystyrene-grafted carbon
      nanotube solutions in tetrahydrofuran (THF) provide wall-to-wall collinearly self
      assembled nanotubes when cast samples are analyzed by transmission electron
      microscopy (TEM). Those self-assemblies are not obtained when suitable blanks are
      similarly cast from analogous solutions containing non-grafted counterparts.
      Therefore, this method enables the modification of the nanotube anisotropic
      patchiness at the sidewalls which results into spontaneous auto-organization at
      the nanoscale.

PMID- 29658934
TI  - Using Brain Activation (nir-HEG/Q-EEG) and Execution Measures (CPTs) in a ADHD
      Assessment Protocol.
AB  - Attention Deficit Hyperactivity Disorder (ADHD) is a problem that impacts
      academic performance and has serious consequences that result in difficulties in
      scholastic, social and familial contexts. One of the most common problems in the
      identification of this disorder relates to the apparent over diagnosis of the
      disorder due to the absence of global protocols for assessment. The research
      group of School Learning, Difficulties and Academic Performance (ADIR) from the
      University of Oviedo, has developed a complete protocol that suggests the
      existence of certain patterns of cortical activation and executive control for
      identifying ADHD more objectively. This protocol takes into consideration some of
      the hypothetical determinants of ADHD, including the relationship between
      activation of selected areas of the brain, and differences in performance on
      various aspects of executive functioning such as omissions, commissions or
      response times, using innovative tools of Continuous Performance Testing (based
      on Virtual Reality CPT and Traditional CPT) and brain activation measures (two
      different tools, based on Hemoencephalography- nirHEG; and Quantified
      Electroencephalography --Q-EEG, respectively). This model of assessment aims to
      provide an effective assessment of ADHD symptomatology in order to design an
      accurate intervention and make appropriate recommendations for parents and
      teachers.

PMID- 29658935
TI  - Fabrication of Custom Agarose Wells for Cell Seeding and Tissue Ring Self
      assembly Using 3D-Printed Molds.
AB  - Engineered tissues are being used clinically for tissue repair and replacement,
      and are being developed as tools for drug screening and human disease modeling.
      Self-assembled tissues offer advantages over scaffold-based tissue engineering,
      such as enhanced matrix deposition, strength, and function. However, there are
      few available methods for fabricating 3D tissues without seeding cells on or
      within a supporting scaffold. Previously, we developed a system for fabricating
      self-assembled tissue rings by seeding cells into non-adhesive agarose wells. A
      polydimethylsiloxane (PDMS) negative was first cast in a machined polycarbonate
      mold, and then agarose was gelled in the PDMS negative to create ring-shaped cell
      seeding wells. However, the versatility of this approach was limited by the
      resolution of the tools available for machining the polycarbonate mold. Here, we
      demonstrate that 3D-printed plastic can be used as an alternative to machined
      polycarbonate for fabricating PDMS negatives. The 3D-printed mold and revised
      mold design is simpler to use, inexpensive to produce, and requires significantly
      less agarose and PDMS per cell seeding well. We have demonstrated that the
      resulting agarose wells can be used to create self-assembled tissue rings with
      customized diameters from a variety of different cell types. Rings can then be
      used for mechanical, functional, and histological analysis, or for fabricating
      larger and more complex tubular tissues.

PMID- 29658936
TI  - Two-dimensional Gel Electrophoresis Coupled with Mass Spectrometry Methods for an
      Analysis of Human Pituitary Adenoma Tissue Proteome.
AB  - Human pituitary adenoma (PA) is a common tumor that occurs in the human pituitary
      gland in the hypothalamus-pituitary-targeted organ axis systems, and may be
      classified as either clinically functional or nonfunctional PA (FPA and NFPA).
      NFPA is difficult for early stage diagnosis and therapy due to barely elevating
      hormones in the blood compared to FPA. Our long-term goal is to use proteomics
      methods to discover reliable biomarkers for clarification of PA molecular
      mechanisms and recognition of effective diagnostic, prognostic markers and
      therapeutic targets. Effective two-dimensional gel electrophoresis (2DE) coupled
      with mass spectrometry (MS) methods were presented here to analyze human PA
      proteomes, including preparation of samples, 2D gel electrophoresis, protein
      visualization, image analysis, in-gel trypsin digestion, peptide mass fingerprint
      (PMF), and tandem mass spectrometry (MS/MS). 2-Dimensional gel electrophoresis
      matrix-assisted laser desorption/ionization mass spectrometry PMF (2DE-MALDI MS
      PMF), 2DE-MALDI MS/MS, and 2DE-liquid chromatography (LC) MS/MS procedures have
      been successfully applied in an analysis of NFPA proteome. With the use of a high
      sensitivity mass spectrometer, many proteins were identified with the 2DE-LC
      MS/MS method in each 2D gel spot in an analysis of complex PA tissue to maximize
      the coverage of human PA proteome.

PMID- 29658937
TI  - Kinematic Analysis Using 3D Motion Capture of Drinking Task in People With and
      Without Upper-extremity Impairments.
AB  - Kinematic analysis is a powerful method for objective assessment of upper
      extremity movements in a three-dimensional (3D) space. Three-dimensional motion
      capture with an optoelectronic camera system is considered as golden standard for
      kinematic movement analysis and is increasingly used as outcome measure to
      evaluate the movement performance and quality after an injury or disease
      involving upper extremity movements. This article describes a standardized
      protocol for kinematic analysis of drinking task applied in individuals with
      upper extremity impairments after stroke. The drinking task incorporates
      reaching, grasping and lifting a cup from a table to take a drink, placing the
      cup back, and moving the hand back to the edge of the table. The sitting position
      is standardized to the individual's body size and the task is performed in a
      comfortable self-paced speed and compensatory movements are not constrained. The
      intention is to keep the task natural and close to a real-life situation to
      improve the ecological validity of the protocol. A 5-camera motion capture system
      is used to gather 3D coordinate positions from 9 retroreflective markers
      positioned on anatomical landmarks of the arm, trunk, and face. A simple single
      marker placement is used to ensure the feasibility of the protocol in clinical
      settings. Custom-made Matlab software provides automated and fast analyses of
      movement data. Temporal kinematics of movement time, velocity, peak velocity,
      time of peak velocity, and smoothness (number of movement units) along with
      spatial angular kinematics of shoulder and elbow joint as well as trunk movements
      are calculated. The drinking task is a valid assessment for individuals with
      moderate and mild upper extremity impairment. The construct, discriminative and
      concurrent validity along with responsiveness (sensitivity to change) of the
      kinematic variables obtained from the drinking task have been established.

PMID- 29658938
TI  - Formaldehyde-assisted Isolation of Regulatory Elements to Measure Chromatin
      Accessibility in Mammalian Cells.
AB  - Appropriate gene expression in response to extracellular cues, that is, tissue-
      and lineage-specific gene transcription, critically depends on highly defined
      states of chromatin organization. The dynamic architecture of the nucleus is
      controlled by multiple mechanisms and shapes the transcriptional output programs.
      It is, therefore, important to determine locus-specific chromatin accessibility
      in a reliable fashion that is preferably independent from antibodies, which can
      be a potentially confounding source of experimental variability. Chromatin
      accessibility can be measured by various methods, including the Formaldehyde
      Assisted Isolation of Regulatory Elements (FAIRE) assay, that allow the
      determination of general chromatin accessibility in a relatively low number of
      cells. Here we describe a FAIRE protocol that allows simple, reliable, and fast
      identification of genomic regions with a low protein occupancy. In this method,
      the DNA is covalently bound to the chromatin proteins using formaldehyde as a
      crosslinking agent and sheared to small pieces. The free DNA is afterwards
      enriched using phenol:chloroform extraction. The ratio of free DNA is determined
      by quantitative polymerase chain reaction (qPCR) or DNA sequencing (DNA-seq)
      compared to a control sample representing total DNA. The regions with a looser
      chromatin structure are enriched in the free DNA sample, thus allowing the
      identification of genomic regions with lower chromatin compaction.

PMID- 29658940
TI  - Separation of Aldehydes and Reactive Ketones from Mixtures Using a Bisulfite
      Extraction Protocol.
AB  - The purification of organic compounds is an essential component of routine
      synthetic operations. The ability to remove contaminants into an aqueous layer by
      generating a charged structure provides an opportunity to use extraction as a
      simple purification technique. By combining the use of a miscible organic solvent
      with saturated sodium bisulfite, aldehydes and reactive ketones can be
      successfully transformed into charged bisulfite adducts that can then be
      separated from other organic components of a mixture by the introduction of an
      immiscible organic layer. Here, we describe a simple protocol for the removal of
      aldehydes, including sterically-hindered neopentyl aldehydes and some ketones,
      from chemical mixtures. Ketones can be separated if they are sterically
      unhindered cyclic or methyl ketones. For aliphatic aldehydes and ketones,
      dimethylformamide is used as the miscible solvent to improve removal rates. The
      bisulfite addition reaction can be reversed by basification of the aqueous layer,
      allowing for the re-isolation of the reactive carbonyl component of a mixture.

PMID- 29658939
TI  - Simultaneous Recordings of Cortical Local Field Potentials, Electrocardiogram,
      Electromyogram, and Breathing Rhythm from a Freely Moving Rat.
AB  - Monitoring the physiological dynamics of the brain and peripheral tissues is
      necessary for addressing a number of questions about how the brain controls body
      functions and internal organ rhythms when animals are exposed to emotional
      challenges and changes in their living environments. In general experiments,
      signals from different organs, such as the brain and the heart, are recorded by
      independent recording systems that require multiple recording devices and
      different procedures for processing the data files. This study describes a new
      method that can simultaneously monitor electrical biosignals, including tens of
      local field potentials in multiple brain regions, electrocardiograms that
      represent the cardiac rhythm, electromyograms that represent awake/sleep-related
      muscle contraction, and breathing signals, in a freely moving rat. The recording
      configuration of this method is based on a conventional micro-drive array for
      cortical local field potential recordings in which tens of electrodes are
      accommodated, and the signals obtained from these electrodes are integrated into
      a single electrical board mounted on the animal's head. Here, this recording
      system was improved so that signals from the peripheral organs are also
      transferred to an electrical interface board. In a single surgery, electrodes are
      first separately implanted into the appropriate body parts and the target brain
      areas. The open ends of all of these electrodes are then soldered to individual
      channels of the electrical board above the animal's head so that all of the
      signals can be integrated into the single electrical board. Connecting this board
      to a recording device allows for the collection of all of the signals into a
      single device, which reduces experimental costs and simplifies data processing,
      because all data can be handled in the same data file. This technique will aid
      the understanding of the neurophysiological correlates of the associations
      between central and peripheral organs.

PMID- 29658941
TI  - Surgical Swine Model of Chronic Cardiac Ischemia Treated by Off-Pump Coronary
      Artery Bypass Graft Surgery.
AB  - Chronic cardiac ischemia that impairs cardiac function, but does not result in
      infarct, is termed hibernating myocardium (HM). A large clinical subset of
      coronary artery disease (CAD) patients have HM, which in addition to causing
      impaired function, puts them at higher risk for arrhythmia and future cardiac
      events. The standard treatment for this condition is revascularization, but this
      has been shown to be an imperfect therapy. The majority of pre-clinical cardiac
      research focuses on infarct models of cardiac ischemia, leaving this subset of
      chronic ischemia patients largely underserved. To address this gap in research,
      we have developed a well-characterized and highly reproducible model of
      hibernating myocardium in swine, as swine are ideal translational models for
      human heart disease. In addition to creating this unique disease model, we have
      optimized a clinically relevant treatment model of coronary artery bypass surgery
      in swine. This allows us to accurately study the effects of bypass surgery on
      heart disease, as well as investigate additional or alternate therapies. This
      model surgically induces single vessel stenosis by implanting a constrictor on
      the left anterior descending (LAD) artery in a young pig. As the pig grows, the
      constrictor creates a gradual stenosis, resulting in chronic ischemia with
      impaired regional function, but preserving tissue viability. Following the
      establishment of the hibernating myocardium phenotype, we perform off-pump
      coronary artery bypass graft surgery to revascularize the ischemic region,
      mimicking the gold-standard treatment for patients in the clinic.

PMID- 29658942
TI  - Neuron-Macrophage Co-cultures to Activate Macrophages Secreting Molecular Factors
      with Neurite Outgrowth Activity.
AB  - There is strong evidence that macrophages can participate in the regeneration or
      repair of injured nervous system. Here, we describe a protocol in which
      macrophages are induced to produce conditioned medium (CM) that promotes neurite
      outgrowth. Adult dorsal root ganglion (DRG) neurons are acutely dissociated and
      plated. After the neurons are stably attached, peritoneal macrophages are co
      cultured on a cell culture insert overlaid on the same well. Dibutyryl cyclic AMP
      (db-cAMP) is applied to the co-cultures for 24 h, after which the cell culture
      insert containing the macrophages is moved to another well to collect CM for 72
      h. The CM from the co-cultures treated with db-cAMP, when applied to a separate
      adult DRG neuron culture, exhibits robust neurite outgrowth activity. The CM
      obtained from the db-cAMP-treated cultures consisting of single cell type alone,
      either DRG neuron or peritoneal macrophage, did not exhibit neurite outgrowth
      activity. This indicates that the interaction between neurons and macrophages is
      indispensable for the activation of macrophages secreting molecular factors with
      neurite outgrowth activity into CM. Thus, our co-culture paradigm will also be
      useful to study intercellular signaling in the neuron-macrophage interaction to
      stimulate the macrophages to be endowed with a pro-regenerative phenotype.

PMID- 29658943
TI  - Deep learning massively accelerates super-resolution localization microscopy.
AB  - The speed of super-resolution microscopy methods based on single-molecule
      localization, for example, PALM and STORM, is limited by the need to record many
      thousands of frames with a small number of observed molecules in each. Here, we
      present ANNA-PALM, a computational strategy that uses artificial neural networks
      to reconstruct super-resolution views from sparse, rapidly acquired localization
      images and/or widefield images. Simulations and experimental imaging of
      microtubules, nuclear pores, and mitochondria show that high-quality, super
      resolution images can be reconstructed from up to two orders of magnitude fewer
      frames than usually needed, without compromising spatial resolution. Super
      resolution reconstructions are even possible from widefield images alone, though
      adding localization data improves image quality. We demonstrate super-resolution
      imaging of >1,000 fields of view containing >1,000 cells in ~3 h, yielding an
      image spanning spatial scales from ~20 nm to ~2 mm. The drastic reduction in
      acquisition time and sample irradiation afforded by ANNA-PALM enables faster and
      gentler high-throughput and live-cell super-resolution imaging.

PMID- 29658946
TI  - Association between overweight and obesity with school performance in secondary
      students in Merida, Mexico.
AB  - Background: Some studies have found a negative relationship between obesity and
      school performance in scholars. However, this topic has not been studied in depth
      in Mexico. The aim of this study was to analyze the association between
      overweight and obesity with school performance in secondary school students from
      Merida. Methods: Weight and height were measured, and body mass index was
      calculated in a sample of 566 secondary students in Merida. Nutritional status
      was classified in normal weight (-2-<+1 standard deviation [SD]), overweight (+1
      <2 SD) and obesity (> + 2 SD) according to the World Health Organization
      criteria. The scores in language, mathematics and sciences were used as
      indicators of school performance. Good performance was considered when the scores
      were >=8 points, and poor performance when scores were <8 points. Logistic
      regression models were used to analyse the association between the variables.
      Results: The 44% of the sample met the criteria for overweight and obesity. After
      adjusting for school grade, type of school, number of absences, and Mayan
      surnames, we found that girls classified as obese had a significant risk of a
      poor performance in mathematics (odds ratio [OR]: 3.07; 95% confidence interval
      [CI]: 1.39-6.80) and language (OR: 2.55; 95% CI: 1.14-5.71) compared with those
      with healthy weight. Conclusions: Our results suggest that obesity represents a
      risk of having a lower school performance in girls but not in boys.

PMID- 29658945
TI  - Experience with OK-432 in lymphatic vascular malformations in a hospital from
      northern Mexico.
AB  - Background: Lymphatic vascular malformations (LVM) or formerly called
      lymphangiomas are congenital malformations present in about 1 out of 6000 to 
      16000 births. The most relevant classification system for lymphangioma management
      is based on the size of the cysts. Spontaneous resolution is uncommon; thus,
      expectant management is not recommended. The classic treatment is excisional
      surgery, but it can affect adjacent structures or have relapses, so, sclerosing
      substances like OK-432 are being studied. The majority of the studies are small
      in number of patients and are from Japan; the largest studies in Mexico are
      focused on specific lesions (macrocystic) or a determined anatomical region. To
      date, there are no studies of the population of the north of Mexico. Method: The
      experience with OK-432 was described through a retrospective, descriptive study
      in patients with LVM, from 2011 to 2016, in a reference hospital of northern
      Mexico. Results: A total of 26 patients with LVM were treated with OK-432. The
      majority of the lesions were macrocystic (69 %), microcystic (19 %) and mixed (12
      %). From the total number of patients, 11 fully healed, and 72 % of the study
      population had >50 % reduction in lesion size, with only 2 applications. There
      were no recurrences. Complications were reported in 2 patients who had skin
      hyperpigmentation. Conclusions: OK-432 probed to be an effective treatment for
      LVM in a reference hospital in the north of Mexico.

PMID- 29658944
TI  - An in vivo model of functional and vascularized human brain organoids.
AB  - Differentiation of human pluripotent stem cells to small brain-like structures
      known as brain organoids offers an unprecedented opportunity to model human brain
      development and disease. To provide a vascularized and functional in vivo model
      of brain organoids, we established a method for transplanting human brain
      organoids into the adult mouse brain. Organoid grafts showed progressive neuronal
      differentiation and maturation, gliogenesis, integration of microglia, and growth
      of axons to multiple regions of the host brain. In vivo two-photon imaging
      demonstrated functional neuronal networks and blood vessels in the grafts.
      Finally, in vivo extracellular recording combined with optogenetics revealed
      intragraft neuronal activity and suggested graft-to-host functional synaptic
      connectivity. This combination of human neural organoids and an in vivo
      physiological environment in the animal brain may facilitate disease modeling
      under physiological conditions.

PMID- 29658947
TI  - Pulmonary sequestration associated with congenital pulmonary airway malformation.
AB  - Introduction: Congenital pulmonary malformations are a rare cause of neonatal
      morbidity. Some of them have a common origin, which allows the identification of
      combined lesions. Its diagnosis can be made prenatally by ultrasound, with the
      limitation that this study is performed in specialized centers and depends on the
      expertise of the operator. The association of pulmonary sequestration and
      congenital malformation of the airway has been described in approximately 40-60
      cases since its first description in 1949. Many lesions are not perceptible in
      intrauterine life and in the neonatal period there are recurrent respiratory
      symptoms that in some cases are associated with a congenital pulmonary
      malformation. Case report: We report the case of a young infant, who was
      diagnosed with pulmonary sequestration at 24 weeks of gestational age, undergoing
      intrauterine surgical treatment with a report of complete resolution of the
      malformation in posterior ultrasounds. She was valued by pediatric pneumology at
      4 months of age, where angiotomography was performed and the presence of
      pulmonary sequestration was confirmed by lobectomy. The histopathological study
      reported extralobar pulmonary sequestration with congenital malformation of the
      pulmonary airway type 2. These combined lesions were identified by
      histopathological study. The treatment of choice was surgical. Conclusions: Upon
      the confirmation of a malformation, we emphasize the importance of performing a
      screening in order to search for other that could be associated.

PMID- 29658948
TI  - Maternal employment and Mexican school-age children overweight in 2012: the
      importance of households features.
AB  - Background: International evidence regarding the relationship between maternal
      employment and school-age children overweight and obesity shows divergent
      results. In Mexico, this relationship has not been confirmed by national data
      sets analysis. Consequently, the objective of this article was to evaluate the
      role of the mothers' participation in labor force related to excess body weight
      in Mexican school-age children (aged 5-11 years). Method: A cross-sectional study
      was conducted on a sample of 17,418 individuals from the National Health and
      Nutrition Survey 2012, applying binomial logistic regression models. Results:
      After controlling for individual, maternal and contextual features, the mothers'
      participation in labor force was associated with children body composition.
      However, when the household features (living arrangements, household ethnicity,
      size, food security and socioeconomic status) were incorporated, maternal
      employment was no longer statically significant. Conclusions: Household features
      are crucial factors for understanding the overweight and obesity prevalence
      levels in Mexican school-age children, despite the mother having a paid job.

PMID- 29658949
TI  - Urinary tract infections, immunity, and vaccination.
AB  - Urinary tract infections (UTI) are considered one of the main causes of morbidity
      worldwide, and uropathogenic Escherichia coli (UPEC) is the etiological agent
      associated with these infections. The high morbidity produced by the UTI and the
      limitation of antibiotic treatments promotes the search for new alternatives
      against these infections. The knowledge that has been generated regarding the
      immune response in the urinary tract is important for the development of
      effective strategies in the UTI prevention, treatment, and control. Molecular
      biology and bioinformatic tools have allowed the construction of fusion proteins
      as biomolecules for the development of a viable vaccine against UTI. The fimbrial
      adhesins (FimH, CsgA, and PapG) of UPEC are virulence factors that contribute to
      the adhesion, invasion, and formation of intracellular bacterial communities. The
      generation of recombinant proteins from fimbrial adhesins as a single molecule is
      obtained by fusion technology. A few in vivo and in vitro studies have shown that
      fusion proteins provide an efficient immune response and protection against UTI
      produced by UPEC. Intranasal immunization of immunogenic molecules has generated
      a response in the urinary tract mucosa compared with other routes of
      immunization. The objective of this review was to propose a vaccine designed
      against UTI caused by UPEC, describing the general scenario of the infection, the
      mechanism of pathogenicity of bacteria, and the immune response of the host.

PMID- 29658950
TI  - Microbial biofilms and their impact on medical areas: physiopathology, diagnosis
      and treatment.
AB  - Biofilms are communities of microorganisms that grow aggregated and surrounded by
      an extracellular matrix, which they produce and favors them to adhere covalently
      to inert and living surfaces; it also helps them to develop high tolerance to
      molecules with antimicrobial activity. Moreover, biofilms are associated with
      chronic and persistent infections, which negatively impact different medical
      areas since they generate high costs to health care systems and patients every
      year because they are difficult to treat with conventional antimicrobial drugs.
      Additionally, they generate high rates of morbidity and mortality. The objective
      of this review was to present extensive and up-to-date information on the origin,
      biosynthesis, and pathophysiology of biofilms. Also, its relationship with
      chronic infections, diagnosis, current antimicrobial treatments with antibiotic
      activity, and perspectives on the search for new treatments, since the latter
      still represent an important area of research.

PMID- 29658951
TI  - Prevalence of plaque and dental decay in the first permanent molar in a school
      population of south Mexico City.
AB  - Background: The first permanent molar is susceptible to acquire tooth decay since
      its eruption, due to its anatomy and because it has been exposed before other
      teeth. Method: An observational, prolective, transversal and comparative study in
      194 students, with an average age of 9.9 +/- 1.8 years. The evaluation of the
      dentobacterial plate (DBP) was analyzed using the O'Leary index and the tooth
      decay experience with the DMFS (sum of decayed, missing, extracted and filling
      dental surfaces) and DMFT (sum of decayed, missing, extracted and filling per
      tooth) indexes. Results: The prevalence of DBP in the first permanent molar was
      of 99.4% and tooth decay of 57.2%. The value of DMFT was 1.4 +/- 1.4. The tooth
      decay experience was higher in children from 7.10 years old with a value of 2.2
      +/- 2.3, who are 7.9 times more likely to develop lesions than younger children
      (odds ratio: 8.9; 95% confidence interval: 4.1-19.5; p < 0.0001). We found an
      association between age and the values of the tooth decay experience indexes;
      even though these were weak in the case of DMF (r = 0.439), the model allowed to
      explain 19% of the association, and 22% for DMFT (r = 0.464). Conclusions: Tooth
      decay develops rapidly in the first permanent molars; however, it does not
      receive the necessary care because it is usually unknown that it is a permanent
      tooth.

PMID- 29658953
TI  - Corrigendum.
AB  - [This corrects the article DOI: 10.1111/j.1447-0578.2006.00148.x.].

PMID- 29658954
TI  - Correction to 'Bifunctional fluorescent probes for detection of amyloid
      aggregates and reactive oxygen species'.
AB  - [This corrects the article DOI: 10.1098/rsos.171399.].

PMID- 29658955
TI  - The effect of a loss of model structural detail due to network skeletonization on
      contamination warning system design: case studies.
AB  - The effect of limitations in the structural detail available in a network model
      on contamination warning system (CWS) design was examined in case studies using
      the original and skeletonized network models for two water distribution systems
      (WDSs). The skeletonized models were used as proxies for incomplete network
      models. CWS designs were developed by optimizing sensor placements for worst-case
      and mean-case contamination events. Designs developed using the skeletonized
      network models were transplanted into the original network model for evaluation.
      CWS performance was defined as the number of people who ingest more than some
      quantity of a contaminant in tap water before the CWS detects the presence of
      contamination. Lack of structural detail in a network model can result in CWS
      designs that (1) provide considerably less protection against worst-case
      contamination events than that obtained when a more complete network model is
      available and (2) yield substantial underestimates of the consequences associated
      with a contamination event. Nevertheless, CWSs developed using skeletonized
      network models can provide useful reductions in consequences for contaminants
      whose effects are not localized near the injection location. Mean-case designs
      can yield worst-case performances similar to those for worst-case designs when
      there is uncertainty in the network model. Improvements in network models for
      WDSs have the potential to yield significant improvements in CWS designs as well
      as more realistic evaluations of those designs. Although such improvements would
      be expected to yield improved CWS performance, the expected improvements in CWS
      performance have not been quantified previously. The results presented here
      should be useful to those responsible for the design or implementation of CWSs,
      particularly managers and engineers in water utilities, and encourage the
      development of improved network models.

PMID- 29658952
TI  - Transcriptional Regulation of the First Cell Fate Decision.
AB  - Understanding how the first cell fate decision has chosen is a fascinating
      biological question that was received consider attention over the last decade.
      Numerous transcription factors are required, and many have been shown to have
      essential roles in this process. Here we reexamine the function that
      transcription factors play primarily in the mouse-the model system most
      thoroughly examined in this process. We address how the first embryonic lineage
      is established and maintained, with a particular emphasis on subsequent
      trophectoderm development and the role of the recently established Arid3a
      transcription factor in this process. In addition, we review relevant aspects of
      embryonic stem cell reprogramming into trophoblast stem cells -the equivalent of
      the epiblast (inner cell mass) and the establishment of induced trophoblast stem
      cells-the in vitro equivalent of the trophectoderm.

PMID- 29658956
TI  - Deletion of the Neurotrophin Receptor p75NTR Prevents Diabetes-Induced Retinal
      Acellular Capillaries in Streptozotocin-Induced Mouse Diabetic Model.
AB  - Diabetic retinopathy is characterized by early stage of retinal neuro
      inflammation that triggers development of acellular capillaries and a late stage
      of pathological neovascularization. Due to limited treatment options, there is a
      pressing need to develop new therapeutics. Our group discovered that diabetes
      impaired processing of the nerve growth factor precursor (proNGF) resulting in
      its accumulation and its receptor p75NTR. Here, we examine the protective effects
      of modulating p75NTR in experimental model of diabetic retinopathy. Diabetes was
      induced using streptozotocin in both wild type (WT) and p75NTR knockout (p75KO)
      mice. Retinal inflammation and microvascular dysfunction were assessed. Western
      blot analysis was performed to assess expression of apoptotic and inflammatory
      markers and levels of the neurotrophin, p75NTR and ephrin-B2. Deletion of p75NTR
      did not alter body weight or diabetes status compared to WT mice. In WT-mice,
      diabetes triggered retinal inflammation, significant decrease in pericyte count
      and marked increase in development of occluded (acellular) capillary formation
      after 24-weeks. Deletion of p75NTR prevented acellular capillary, restored
      pericyte count, and inhibited the retinal Ephrin-B2, activation of the stress
      kinase JNK and apoptotic marker cleaved caspase-3 in the diabetic retina.
      Deletion of p75NTR reduced retinal inflammation, and proNGF expression. These
      effects coincided with increased NGF level and TrkA activation in the diabetic
      retina. Targeting p75NTR using genetic approach protected the retina from the
      impact of long-term diabetes in mediating microvascular degeneration and
      maintains the balance of NGF/proNGF level. Together, these results provide
      rationale that targeting p75NTR may offer novel and effective therapeutic
      strategy to combat diabetic retinopathy.

PMID- 29658957
TI  - Corrigendum: Factors Affecting Quality and Health Promoting Compounds during
      Growth and Postharvest Life of Sweet Cherry (Prunus avium L.).
AB  - [This corrects the article on p. 2166 in vol. 8, PMID: 29312407.].

PMID- 29658958
TI  - Treatment with Src inhibitor Dasatinib results in elevated metastatic potential
      in the 4T1 murine mammary carcinoma model.
AB  - Introduction: The src inhibitor Dasatinib has been widely studied as an anti
      metastatic agent. The aims of this study were to examine the effect of Src
      inhibition on the metastatic potential of the 4T1 murine mammary carcinoma.
      Context: Src is a non-receptor tyrosine kinase well-known to contribute to the
      metastatic potential of tumour cells. It does so through alteration of signalling
      pathways important to metastasis. Elevated levels of Src are common in many
      cancer types, and have been correlated with tumour progression and poor patient
      prognosis. Aims: This study examined whether disruption of the Src signalling
      pathway could inhibit metastases formation. Settings and Design: The Src
      inhibitor Dasatinib was evaluated in vitro and in vivo using the highly
      metastatic 4T1 murine mammary adenocarcinoma cell line. Methods and Material: In
      vitro assays included growth curve, western blot, migration, and invasion assays.
      In vivo assays included intradermal and tail vein injection models. Statistical
      analysis used: In vitro data were analysed using one-way ANOVA with Dunnett's
      multiple comparisons in GraphPad Prism 6.0. In vivo data were analysed using
      GraphPad Prism 6.0, using the Wilcoxon matched pairs test. Results: Dasatinib is
      effective at inhibiting in vitro phosphorylation of Src, migration and invasion
      in the 4T1 cell line, as well as angiogenesis in vivo. In vitro treatment with
      Dasatinib impaired the metastatic ability of tumour cells as assessed by a tail
      vein injection model. However, both the syngeneic BALB/c and the athymic nu/nu
      mice receiving oral doses of the drug developed significantly higher numbers of
      4T1 lung metastases. This effect was not seen in a different breast carcinoma
      cell line, the MDA-MB-231-4175-LM2, nor was this effect seen in the murine
      fibrosarcoma KHT cell line. Conclusions: The 4T1 cell line is not an appropriate
      model to study Src inhibition.

PMID- 29658959
TI  - Are Gasoline Prices a Factor in Residential Relocation Decisions? Preliminary
      Findings from the American Housing Survey, 1996-2008.
AB  - Residential relocation choice is affected by numerous factors, but gasoline
      prices as a potential factor have not been investigated. This study examines
      gasoline price changes and residential relocation choice using 1996-2008 American
      Housing Survey data. We found higher gasoline prices are associated with a higher
      percentage of movers choosing locations closer to workplaces. The findings have
      implications for addressing the impacts of volatile gasoline prices on land use
      planning and policies; resilient "smart cities or communities" are one possible
      solution.

PMID- 29658960
TI  - Entropy of Convex Functions on R d.
AB  - Let Omega be a bounded closed convex set in R d with non-empty interior, and let
      ?? r (Omega) be the class of convex functions on Omega with Lr -norm bounded by
      1. We obtain sharp estimates of the epsilon-entropy of ?? r (Omega) under Lp
      (Omega) metrics, 1 <= p < r <= infinity. In particular, the results imply that
      the universal lower bound epsilon-d/2 is also an upper bound for all d-polytopes,
      and the universal upper bound of [Formula: see text] for [Formula: see text] is
      attained by the closed unit ball. While a general convex body can be approximated
      by inscribed polytopes, the entropy rate does not carry over to the limiting
      body. Our results have applications to questions concerning rates of convergence
      of nonparametric estimators of high-dimensional shape-constrained functions.

PMID- 29658961
TI  - Correction to 'Multiple optimality criteria support Ornithoscelida'.
AB  - [This corrects the article DOI: 10.1098/rsos.170833.].

PMID- 29658963
TI  - Correction to 'The reproducibility of research and the misinterpretation of p
      values'.
AB  - [This corrects the article DOI: 10.1098/rsos.171085.].

PMID- 29658962
TI  - A Pilot Randomized Controlled Trial of a New Supplementary Food Designed to
      Enhance Cognitive Performance during Prevention and Treatment of Malnutrition in
      Childhood.
AB  - Background: Cognitive impairment associated with childhood malnutrition and
      stunting is generally considered irreversible. Objective: The aim was to test a
      new nutritional supplement for the prevention and treatment of moderate-acute
      malnutrition (MAM) focused on enhancing cognitive performance. Methods: An 11-wk,
      village-randomized, controlled pilot trial was conducted in 78 children aged 1-3
      or 5-7 y living in villages in Guinea-Bissau. The supplement contained 291 kcal/d
      for young children and 350 kcal/d for older children and included 5 nutrients and
      2 flavan-3-ol-rich ingredients not present in current food-based recommendations
      for MAM. Local bakers prepared the supplement from a combination of locally
      sourced items and an imported mix of ingredients, and it was administered by
      community health workers 5 d/wk. The primary outcome was executive function
      abilities at 11 wk. Secondary outcomes included additional cognitive measures and
      changes in z scores for weight (weight-for-age) and height (height-for-age) and
      hemoglobin concentrations at 11 wk. An index of cerebral blood flow (CBF) was
      also measured at 11 wk to explore the use of this measurement as a biological
      index of cognitive impairment. Results: There were no significant differences in
      any outcome between groups at baseline. There was a beneficial effect of random
      assignment to the supplement group on working memory at 11 wk in children aged 1
      3 y (P < 0.05). This difference contrasted with no effect in older children and
      was not associated with faster growth rate. In addition, CBF correlated with task
      switching performance (P < 0.05). Conclusions: These preliminary data suggest
      that cognitive impairment can be monitored with measurement of CBF. In addition,
      the findings provide preliminary data that suggest that it may be possible to
      improve poor cognitive performance in young children through changes in the
      nutritional formulation of supplementary foods used to prevent and treat MAM.
      Powered studies of the new supplement formulation are needed. This trial was
      registered at clinicaltrials.gov as NCT03017209.

PMID- 29658964
TI  - Micropassage-embedding composite hydrogel fibers enable quantitative evaluation
      of cancer cell invasion under 3D coculture conditions.
AB  - Cell migration and invasion are of significant importance in physiological
      phenomena, including wound healing and cancer metastasis. Here we propose a new
      system for quantitatively evaluating cancer cell invasion in a three-dimensional
      (3D), in vivo tissue-like environment. This system uses composite hydrogel
      microfibers whose cross section has a relatively soft micropassage region and
      that were prepared using a multilayered microfluidic device; cancer cells are
      encapsulated in the core and fibroblasts are seeded in the shell regions
      surrounding the core. Cancer cell proliferation is guided through the
      micropassage because of the physical restriction imposed by the surrounding solid
      shell regions. Quantitative analysis of cancer cell invasion is possible simply
      by counting the cancer cell colonies that form outside the fiber. This platform
      enables the evaluation of anticancer drug efficacy (cisplatin, paclitaxel, and 5
      fluorouracil) based on the degree of invasion and the gene expression of cancer
      cells (A549 cells) with or without the presence of fibroblasts (NIH-3T3 cells).
      The presented hydrogel fiber-based migration assays could be useful for studying
      cell behaviors under 3D coculture conditions and for drug screening and
      evaluation.

PMID- 29658965
TI  - A comprehensive transcriptome analysis of skeletal muscles in two Polish pig
      breeds differing in fat and meat quality traits.
AB  - Pork is the most popular meat in the world. Unfortunately, the selection pressure
      focused on high meat content led to a reduction in pork quality. The present
      study used RNA-seq technology to identify metabolic process genes related to pork
      quality traits and fat deposition. Differentially expressed genes (DEGs) were
      identified between pigs of Pulawska and Polish Landrace breeds for two the most
      important muscles (semimembranosus and longissimus dorsi). A total of 71
      significant DEGs were reported: 15 for longissimus dorsi and 56 for
      semimembranosus muscles. The genes overexpressed in Pulawska pigs were involved
      in lipid metabolism (APOD, LXRA, LIPE, AP2B1, ENSSSCG00000028753 and OAS2) and
      proteolysis (CST6, CTSD, ISG15 and UCHL1). In Polish Landrace pigs, genes playing
      a role in biological adhesion (KIT, VCAN, HES1, SFRP2, CDH11, SSX2IP and PCDH17),
      actin cytoskeletal organisation (FRMD6, LIMK1, KIF23 and CNN1) and calcium ion
      binding (PVALB, CIB2, PCDH17, VCAN and CDH11) were transcriptionally more active.
      The present study allows for better understanding of the physiological processes
      associated with lipid metabolism and muscle fiber organization. This information
      could be helpful in further research aiming to estimate the genetic markers.

PMID- 29658966
TI  - Methylation in the promoter regions of WT1, NKX6-1 and DBC1 genes in cervical
      cancer tissues of Uygur women in Xinjiang.
AB  - This study aimed to explore: 1) DNA methylation in the promoter regions of Wilms
      tumor gene 1 (WT1), NK6 transcription factor related locus 1 gene (NKX6-1) and
      Deleted in bladder cancer 1 (DBC1) gene in cervical cancer tissues of Uygur women
      in Xinjiang, and 2) the correlation of gene methylation with the infection of
      HPV16/18 viruses. We detected HPV16/18 infection in 43 normal cervical tissues,
      30 cervical intraepithelial neoplasia lesions (CIN) and 48 cervical cancer
      tissues with polymerase chain reaction (PCR) method. Methylation in the promoter
      regions of the WT1, NKX6-1 and DBC1 genes in the above-mentioned tissues was
      measured by methylation-specific PCR (MSP) and cloning sequencing. The expression
      level of these three genes was measured by real-time PCR (qPCR) in 10 methylation
      positive cervical cancer tissues and 10 methylation-negative normal cervical
      tissues. We found that the infection of HPV16 in normal cervical tissues, CIN and
      cervical cancer tissues was 14.0, 36.7 and 66.7%, respectively. The infection of
      HPV18 was 0, 6.7 and 10.4%, respectively. The methylation rates of WT1, NKX6-1
      and DBC1 genes were 7.0, 11.6 and 23.3% in normal cervical tissues, 36.7, 46.7
      and 30.0% in CIN tissues, and 89.6, 77.1 and 85.4% in cervical cancer tissues.
      Furthermore, WT1, NKX6-1 and DBC1 genes were hypermethylated in the high-grade
      squamous intraepithelial lesion (CIN2, CIN3) and in the cervical cancer tissues
      with infection of HPV16/18 (both P< 0.05). The expression of WT1, NKX6-1 and DBC1
      was significantly lower in the methylation-positive cervical cancer tissues than
      in methylation-negative normal cervical tissues. Our findings indicated that
      methylation in the promoter regions of WT1, NKX6-1 and DBC1 is correlated with
      cervical cancer tumorigenesis in Uygur women. The infection of HPV16/18 might be
      correlated with methylation in these genes. Gene inactivation caused by
      methylation might be related to the incidence and development of cervical cancer.

PMID- 29658967
TI  - Identification of microRNA signature in different pediatric brain tumors.
AB  - Understanding pediatric brain tumor biology is essential to help on disease
      stratification, and to find novel markers for early diagnosis. MicroRNA (miRNA)
      expression has been linked to clinical outcomes and tumor biology. Here, we aimed
      to detect the expression of different miRNAs in different pediatric brain tumor
      subtypes to discover biomarkers for early detection and develop novel therapies.
      Expression of 82 miRNAs was detected in 120 pediatric brain tumors from fixed
      formalin paraffin-embedded tissues, low-grade glioma, high-grade glioma,
      ependymoma, and medulloblastoma, using quantitative real-time PCR. Low-expression
      of miR-221, miR-9, and miR-181c/d and over-expression of miR-101, miR-222, miR
      139, miR-1827, and miR-34c was found in medulloblastoma; low expression of miR
      10a and over-expression of miR-10b and miR-29a in ependymoma; low expression of
      miR-26a and overexpression of miR-19a/b, miR-24, miR-27a, miR- 584, and miR-527
      in low-grade glioma. Cox regression showed differential miRNA expression between
      responders and non-responders. The most specific were miR-10a and miR-29a low
      expression in LGG non-responders, miR-135a and miR-146b over-expression in
      ependymoma non-responders, and miR-135b overexpression in medulloblastoma non
      responders. MicroRNAs are differentially expressed in subtypes of brain tumors
      suggesting that they may help diagnosis. A greater understanding of aberrant
      miRNA in pediatric brain tumors may support development of novel therapies.

PMID- 29658968
TI  - Comet and cytogenetic tests as tools for evaluating genomic instability in seeds
      of Oryza sativa L. and Phaseolus vulgaris L. from gene banks.
AB  - This study aimed to assess the feasibility of comet and cytogenetic tests as
      tools for evaluating genomic instability in seeds of Oryza sativa L. (rice) and
      Phaseolus vulgaris (beans) L. from gene banks. Rice and beans were exposed to
      methyl methanesulfonate (MMS) as a reference DNA damaging agent. Seeds of two
      accessions of rice and beans were obtained from Embrapa Rice and Beans - Brazil.
      Seed groups were imbibed in three concentrations of MMS for three periods of time
      to carry out cytogenetic tests, and for one period for the comet test. At
      concentrations of 10 and 15 mg/L, MMS induced cytotoxic and/or mutagenic effects
      in the meristematic cells of roots from all the accessions of both species. In
      the comet test, MMS induced genotoxic effects at all the concentrations in the
      evaluated accessions of rice and beans, except in one accession of beans at the
      lowest concentration (5 mg/L). Both species showed sensitivity to MMS. The comet
      test can be proposed for the measurement of genomic instability in accessions of
      rice and beans in gene banks, as being more sensitive than the cytogenetic tests
      used.

PMID- 29658969
TI  - Combined GSTM1 and GSTT1 null genotypes are strong risk factors for atherogenesis
      in a Serbian population.
AB  - Oxidative stress (OS) plays an important role in atherogenesis and since
      glutathione S-transferases (GSTs) provide protection against OS, we have tested
      the hypothesis that deletion polymorphisms in two GSTs (GSTM1 and GSTT1) may
      affect the risk of developing atherosclerosis. A total of 382 individuals (200
      patients with atherosclerosis and 182 healthy controls) were included in this
      association study. Genomic DNA was isolated from peripheral blood cells or from
      buccal epithelial cells and genotyping was performed using multiplex-PCR or real
      time PCR methods. GSTM1 null genotype was significantly more frequent in
      atherosclerotic patients than in controls (52.0% vs 34.1%) and individuals with
      the GSTM1 null genotype had an approximately 2-fold increase in atherosclerosis
      risk (OR: 2.1, 95%CI=1.39-3.17, P=0.0004). GSTT1 null genotype alone did not show
      a statistically significant effect on atherosclerosis risk modulation, but the
      association approached significance (OR: 1.57, 95%CI=0.94-2.64, P=0.08). The
      combined analysis showed that the presence of both genes had a protective effect
      against atherosclerosis (OR=0.55, 95%CI=0.37-0.83, P=0.005) while double null
      genotypes led to a robust atherosclerosis risk increase (OR: 8.14, 95%CI= 2.41
      27.51, P < 0.0001). This study demonstrated that the GSTM1 null and combined
      GSTM1/GSTT1 null genotypes are susceptibility factors for development of
      atherosclerosis in a Serbian population.

PMID- 29658970
TI  - Differential gene expression profiles in peripheral blood in Northeast Chinese
      Han people with acute myocardial infarction.
AB  - This study aimed to use gene chips to investigate differential gene expression
      profiles in the occurrence and development of acute myocardial infarction (AMI).
      The study included 12 AMI patients and 12 healthy individuals. Total mRNA of
      peripheral bloodwas extracted and reversed-transcribed to cDNA for microarray
      analysis. After establishing two pools with three subjects each (3 AMI patients
      and 3 healthy individuals), the remaining samples were used for RT-qPCR to
      confirm the microarray data. From the microarray results, seven genes were
      randomly selected for RT-qPCR. RT-qPCR results were analyzed by the 2
      DeltaDeltaCt method. Microarray analysis showed that 228 genes were up- regulated
      and 271 were down-regulated (p <= 0.05, |logFC| > 1). Gene ontology showed that
      these genes belong to 128 cellular components, 521 biological processes, and 151
      molecular functions. KEGG pathway analysis showed that these genes are involved
      in 107 gene pathways. RT-qPCR results for the seven genes showed expression
      levels consistent with those obtained by microarray. Thus, microarray data could
      be used to select the pathogenic genes for AMI. Investigating the abnormal
      expression of these differentially expressed genes might suggest efficient
      strategies for the prevention, diagnosis, and treatment of AMI.

PMID- 29658971
TI  - Characterization and expression of the ABC family (G group) in 'Dangshansuli'
      pear (Pyrus bretschneideri Rehd.) and its russet mutant.
AB  - The plant genes encoding ABCGs that have been identified to date play a role in
      suberin formation in response to abiotic and biotic stress. In the present study,
      80 ABCG genes were identified in 'Dangshansuli' Chinese white pear and designated
      as PbABCGs. Based on the structural characteristics and phylogenetic analysis,
      the PbABCG family genes could be classified into seven main groups: classes A-G.
      Segmental and dispersed duplications were the primary forces underlying the
      PbABCG gene family expansion in 'Dangshansuli' pear. Most of the PbABCG
      duplicated gene pairs date to the recent whole-genome duplication that occurred
      30~45 million years ago. Purifying selection has also played a critical role in
      the evolution of the ABCG genes. Ten PbABCG genes screened in the transcriptome
      of 'Dangshansuli' pear and its russet mutant 'Xiusu' were validated, and the
      expression levels of the PbABCG genes exhibited significant differences at
      different stages. The results presented here will undoubtedly be useful for
      better understanding of the complexity of the PbABCG gene family and will
      facilitate the functional characterization of suberin formation in the russet
      mutant.

PMID- 29658972
TI  - Genetic and phenotypic variability of iris color in Buenos Aires population.
AB  - The aim of this work was to describe the phenotypic and genotypic variability
      related to iris color for the population of Buenos Aires province (Argentina),
      and to assess the usefulness of current methods of analysis for this country. We
      studied five Single Nucleotide Polymorphisms (SNPs) included in the IrisPlex kit,
      in 118 individuals, and we quantified eye color with Digital Iris Analysis Tool.
      The markers fit Hardy-Weinberg equilibrium for the whole sample, but not for
      rs12913832 within the group of brown eyes (LR=8.429; p=0.004). We found a
      remarkable association of HERC2 rs12913832 GG with blue color (p < 0.01) but the
      other markers did not show any association with iris color. The results for the
      Buenos Aires population differ from those of other populations of the world for
      these polymorphisms (p < 0,01). The differences we found might respond to the
      admixed ethnic composition of Argentina; therefore, methods of analysis used in
      European populations should be carefully applied when studying the population of
      Argentina. These findings reaffirm the importance of this investigation in the
      Argentinian population for people identification based on iris color.

PMID- 29658974
TI  - Physician Rating Scales Do Not Accurately Rate Physicians.
AB  - The purpose of this study was to determine the proportion of questions used by
      online physician rating scales to directly rate physicians themselves. A
      systematic review was performed of online, patient-reported physician rating
      scales. Fourteen websites were identified containing patient-reported physician
      rating scales, with the most common questions pertaining to office staff
      courtesy, wait time, overall rating (entered, not calculated), trust/confidence
      in physician, and time spent with patient. Overall, 28% directly rated the
      physician, 48% rated both the physician and the office, and 24% rated the office
      alone. There is great variation in the questions used, and most fail to directly
      rate physicians themselves. [Orthopedics. 2018; 41(4):e445-e456.].

PMID- 29658973
TI  - Searching for ancient balanced polymorphisms shared between Neanderthals and
      Modern Humans.
AB  - Hominin evolution is characterized by adaptive solutions often rooted in
      behavioral and cognitive changes. If balancing selection had an important and
      long-lasting impact on the evolution of these traits, it can be hypothesized that
      genes associated with them should carry an excess of shared polymorphisms (trans-
      SNPs) across recent Homo species. In this study, we investigate the role of
      balancing selection in human evolution using available exomes from modern (Homo
      sapiens) and archaic humans (H. neanderthalensis and Denisovan) for an excess of
      trans-SNP in two gene sets: one associated with the immune system (IMMS) and
      another one with behavioral system (BEHS). We identified a significant excess of
      trans-SNPs in IMMS (N=547), of which six of these located within genes previously
      associated with schizophrenia. No excess of trans-SNPs was found in BEHS, but
      five genes in this system harbor potential signals for balancing selection and
      are associated with psychiatric or neurodevelopmental disorders. Our approach
      evidenced recent Homo trans-SNPs that have been previously implicated in
      psychiatric diseases such as schizophrenia, suggesting that a genetic repertoire
      common to the immune and behavioral systems could have been maintained by
      balancing selection starting before the split between archaic and modern humans.

PMID- 29658975
TI  - Thumb Basal Joint Arthroplasty: Prospective Comparison of Perioperative Analgesia
      and Opioid Consumption.
AB  - Trapeziectomy alone or in combination with a suspensionplasty technique is a
      common surgical treatment for symptomatic thumb basal joint arthritis. The
      authors undertook a prospective comparative study to test the hypothesis that
      peripheral nerve blocks would provide better pain control than local anesthesia
      with bupivacaine or liposomal bupivacaine regarding pain scores and opioid pill
      consumption. Patients who elected to undergo basal joint arthroplasty were
      allocated to 1 of 3 postoperative pain management groups: (1) peripheral nerve
      block, (2) local anesthesia with bupivacaine, or (3) local anesthesia with
      liposomal bupivacaine. Total opioid pill consumption and visual analog scale pain
      scores were reported for the first 5 postoperative days (PODs). Seventy-eight
      patients were enrolled, with 27, 23, and 28 patients in the peripheral nerve
      block, bupivacaine, and liposomal bupivacaine groups, respectively. All groups
      experienced an increase in opioid pill consumption and visual analog scale pain
      scores from POD 0 to POD 1. Postoperative visual analog scale pain scores were
      lowest in group 3 from POD 0 to POD 2. Average visual analog scale pain scores
      were highest in group 1, except for on POD 0. After POD 2, visual analog scale
      pain scores normalized between all groups and decreased uniformly thereafter.
      Total opioid consumption was lowest in group 3 (average, 11 pills) compared with
      group 1 (average, 17 pills) and group 2 (average, 19 pills). Overall, these
      findings did not support the authors' hypothesis that peripheral nerve blocks are
      superior in terms of postoperative pain control and opioid consumption. Although
      there were advantages regarding opioid consumption and pain control with
      liposomal bupivacaine, these were limited to the first POD. The effectiveness of
      each modality, as well as potential risks and costs, should be considered when
      determining the optimal strategy. [Orthopedics. 2018; 41(3):e410-e415.].

PMID- 29658976
TI  - Current Trends in the Use of Shoulder Arthroplasty in the United States.
AB  - Reverse total shoulder arthroplasty (rTSA) has become increasingly popular since
      its introduction to the United States. The purpose of this study was to assess
      the current trends and use of rTSA, anatomic total shoulder arthroplasty (aTSA),
      and hemiarthroplasty (HA) from 2011 to 2014. Shoulder arthroplasty data from the
      National (Nationwide) Inpatient Sample database were analyzed for the years 2011
      to 2014 using International Classification of Diseases, Ninth Revision, Clinical
      Modification procedure codes. For each procedure, use and patient and hospital
      characteristics were identified. Shoulder arthroplasties increased by 24% between
      2011 and 2014, to 79,105 procedures. The proportion of arthroplasties that were
      aTSA did not change substantially (44% for both years; P=.0585), while the
      proportion that were rTSA surpassed aTSA in 2014, increasing from 33% to 46%
      (P<.0001). Use of rTSA topped use of aTSA by 2013 for Medicare patients. The
      proportion that were HA procedures declined from 23% to 11% (P<.0001). The use of
      rTSA for fracture increased from 26% to 58% (P<.0001) of all arthroplasties for
      this indication, while the use of HA for fracture decreased from 69% to 40%
      (P<.0001). Orthopedists performed rTSA more often than aTSA for Medicare patients
      by 2013 and the general population by 2014. The use of rTSA for fracture has
      grown significantly, with rTSA being performed more frequently than HA for this
      indication. [Orthopedics. 2018; 41(3):e416-e423.].

PMID- 29658977
TI  - A Systematic Review and Meta-Analysis of Procalcitonin as a Marker of
      Postoperative Orthopedic Infections.
AB  - Procalcitonin is a serologic marker that increases in response to inflammatory
      stimuli, especially those of bacterial origin. Postoperative orthopedic
      periprosthetic infections are often difficult to diagnose. This study
      systematically reviewed the literature to evaluate the statistical measures of
      performance of procalcitonin as a marker of postoperative orthopedic infection.
      This study showed that procalcitonin has a weighted pooled sensitivity of 67.3%,
      specificity of 69.4%, positive likelihood ratio of 1.778, negative likelihood
      ratio of 0.423, and diagnostic odds ratio of 5.770. These results illustrate that
      procalcitonin is an effective serologic marker for postoperative bacterial
      infections. [Orthopedics. 2018; 41(3):e303-e309.].

PMID- 29658978
TI  - Innovation and Entrepreneurship: Perspectives From Orthopedic Surgery.
AB  - Orthopedic surgeons are tasked with treating complex patients while employing
      critical surgical skills, clinical knowledge, and new technologies. The constant
      inundation of information, coupled with hours in the hospital setting, provides
      unique perspectives on various aspects of how health care is delivered, thereby
      creating a milieu ripe for innovation. The rigors of an orthopedic career make it
      challenging for physicians to translate an idea into a great product. Through the
      authors' experiences at a tertiary orthopedic practice, they review the process
      of taking an idea from concept to fruition. [Orthopedics. 2018; 41(3):135-140.].

PMID- 29658979
TI  - Mini-Fragment Fixation Is Equivalent to Bicortical Screw Fixation for Horizontal
      Medial Malleolus Fractures.
AB  - Horizontal fractures of the medial malleolus occur through application of valgus
      or abduction force through the ankle that creates a tension failure of the medial
      malleolus. The authors hypothesize that mini-fragment T-plates may offer improved
      fixation, but the optimal fixation construct for these fractures remains unclear.
      Forty synthetic distal tibiae with identical osteotomies were randomized into 4
      fixation constructs: (1) two parallel unicortical cancellous screws; (2) two
      parallel bicortical cortical screws; (3) a contoured mini-fragment T-plate with 2
      unicortical screws in the fragment and 2 bicortical screws in the shaft; and (4)
      a contoured mini-fragment T-plate with 2 bicortical screws in the fragment and 2
      unicortical screws in the shaft. Specimens were subjected to offset axial tension
      loading on a servohydraulic testing system and tracked using high-resolution
      video. Failure was defined as 2 mm of articular displacement. Analysis of
      variance followed by a Tukey-Kramer post hoc test was used to assess for
      differences between groups, with significance defined as P<.05. The mean
      stiffness (+/-SD) values of both mini-fragment T-plate constructs (239+/-83 N/mm
      and 190+/-37 N/mm) and the bicortical screw construct (240+/-17 N/mm) were not
      statistically different. The mean stiffness values of both mini-fragment T-plate
      constructs and the bicortical screw construct were higher than that of a parallel
      unicortical screw construct (102+/-20 N/mm). Contoured T-plate constructs provide
      stiffer initial fixation than a unicortical cancellous screw construct. The T
      plate is biomechanically equivalent to a bicortical screw construct, but may be
      superior in capturing small fragments of bone. [Orthopedics. 2018; 41(3):e395
      e399.].

PMID- 29658980
TI  - Relative Complications and Trends of Outpatient Total Shoulder Arthroplasty.
AB  - Outpatient arthroplasty is an appealing option among select patient populations
      as a mechanism for reducing health care expenditure. The purpose of this study
      was to determine the nationwide trends and complication profile of outpatient
      total shoulder arthroplasty (TSA). The authors reviewed a national administrative
      claims database to identify patients undergoing TSA as outpatients and inpatients
      from 2007 to 2016. The incidence of perioperative surgical and medical
      complications was determined by querying for relevant International
      Classification of Diseases, Ninth Revision, and Current Procedural Terminology
      codes. Multivariate logistic regression adjusted for age, sex, and Charlson
      Comorbidity Index was used to calculate odds ratios of complications among
      outpatients relative to inpatients undergoing TSA. The query identified 1555
      patients who underwent outpatient TSA and 15,987 patients who underwent inpatient
      TSA. The median age was in the 70 to 74 years age group in both the outpatient
      and the inpatient cohorts, and the age distribution was comparable between the 2
      cohorts (P=.287). The incidence of both outpatient (P<.001) and inpatient
      (P<.001) TSA increased during the study period. On adjustment for age, sex, and
      comorbidities, patients undergoing outpatient TSA had significantly lower rates
      of stiffness requiring manipulation under anesthesia (outpatient, 1.09%;
      inpatient, 2.35%; odds ratio, 0.52; 95% confidence interval, 0.38-0.71; P<.001)
      and higher rates of postoperative surgical site infections requiring reoperation
      (outpatient, 0.90%; inpatient, 0.65%; odds ratio, 1.65; 95% confidence interval,
      1.15-2.35; P<.001) at 1 year. Rates of all other postoperative complications were
      comparable. Ambulatory TSA is increasing in incidence nationwide and is
      associated with an overall favorable postoperative complication profile.
      [Orthopedics. 2018; 41(3):e400-e409.].

PMID- 29658981
TI  - Mobility device use in people with Parkinson's disease: A 3-year follow-up study.
AB  - OBJECTIVES: This study aimed to investigate how the use and perceived unmet need
      of mobility devices (MD) in people with Parkinson's disease (PD) evolve over a 3
      year period. METHODS: The study reports baseline assessments (n = 255) and
      comparisons for participants with complete data at baseline and the 3-year follow
      up (n = 165). Structured questions addressed the use and perceived unmet need of
      various MDs indoor and outdoor (eg, canes, wheeled walkers, and manual and
      powered wheelchairs). McNemar tests were used to investigate differences over
      time. RESULTS: In the total sample at baseline, 30% and 52% of the participants
      reported using MDs indoors and outdoors, respectively. Among those with complete
      data also at the 3-year follow-up, the proportion of participants using MDs
      increased significantly (P < .001) from 22% to 40% for indoors and from 48% to
      66% for outdoors, with transition of MD toward more assistive potential (ie,
      wheeled walker and manual wheelchair). Wheeled walkers were the most commonly
      used MD indoors as well as outdoors on both occasions. Among the users of
      multiple MDs, the most common combination was cane and wheeled walker on both
      occasions. The proportion of participants who reported a perceived unmet need of
      MDs was 5% at baseline, whereas it was 21%, 3 years later. CONCLUSIONS: The use
      and perceived unmet need of MDs in people with PD increase over time. There is a
      need for addressing MDs at clinical follow-ups of people with PD, with continuous
      attention in primary health care and municipality contexts.

PMID- 29658982
TI  - Behavioural changes in patients with intellectual disability treated with
      brivaracetam.
AB  - OBJECTIVE: The purpose of this study was to evaluate the tolerability and
      efficacy of brivaracetam (BRV) in residential patients at our epilepsy centre.
      PATIENTS AND METHODS: We assessed retrospectively 33 patients (14 females; mean
      age 38.2 years, with range 17-63 years) with intellectual disability (ID) and
      drug-resistant epilepsy using an industry-independent, non-interventional study
      design based on standardized daily seizure records. Mean seizure frequency was
      compared between the 3-month baseline period and subsequent 3-month treatment
      period. Evaluation, including calculation of retention rate, was carried out for
      the intervals 3-6 and 9-12 months after brivaracetam initiation. Responders were
      defined as having a 50% reduction in seizure frequency. The Clinical Global
      Impression scale (CGI) was applied to allow assessment of qualitative changes in
      seizure severity, and the Aggressive Behaviour Scale (ABS) gave further insights
      into challenging behaviour. RESULTS: The responder rate was 19%, and one non
      responder attained an improvement in CGI score. The retention rate after 12
      months was 37%. Brivaracetam treatment was stopped because of adverse events (n =
      3), lack of efficacy (n = 8) or both (n = 6). Thirteen patients experienced
      behavioural changes, with aggressive behaviour being the commonest effect. We
      also observed ataxia (n = 2), gastrointestinal disorder (n = 3) and sedation (n =
      2). The ABS showed deterioration, or new occurrence, of aggressive behaviour in
      13 patients. CONCLUSIONS: Brivaracetam seems to be effective in a small number of
      patients suffering from difficult-to-treat epilepsy and intellectual disability.
      Challenging behaviour was documented in a relevant number of patients, with
      psychiatric illness being a risk factor for this.

PMID- 29658983
TI  - Subclinical vestibular dysfunction in migraineurs without vertigo: A Clinical
      study.
AB  - OBJECTIVES: This observational study aimed to investigate the presence of
      potential vestibular system subclinical dysfunction among migraineurs without a
      history of vertigo and dizziness compared with healthy controls. METHODS:
      Patients diagnosed with episodic migraine with and without aura were enrolled.
      All patients and healthy controls underwent vestibular examination using the
      following conventional tests: sitting position, Pagnini-McClure's, Dix
      Hallpike's, head hanging, video head impulse, subjective visual vertical,
      Romberg, Fukuda, and caloric vestibular stimulation by Fitzgerald-Hallpike's
      tests. Nystagmus and angular velocity of the slow phase during culmination phase
      was analyzed by video-nystagmography. RESULTS: Overall, 33 patients (76% female,
      7 with aura and 26 without aura; mean age (mean +/- SD): 29.1 +/- 4.3 years) and
      22 controls (33% female, mean age: 30.8 +/- 9.4 years) were enrolled. There were
      no statistically significant differences in demographic features between patients
      and controls. Caloric vestibular stimulation test results were found to differ
      among patients and controls. In particular, right and left angular velocity (AV)
      were highly correlated one another (r = 0.88, P < .001). Right AV (53.0 +/- 6.7
      vs 44.0 +/- 9.6) and left AV (54.3 +/- 5.3 vs 43.3 +/- 9.0) were statistically
      higher in migraineurs as compared to controls (P < .001). Also right V-HIT (1.1
      +/- 0.1 vs 0.8 +/- 0.4) and left V-HIT (1.1 +/- 0.1 vs 0.7 +/- 0.2) were
      statistically higher in migraineurs compared to controls (P < .001). CONCLUSION:
      Our findings suggest a subclinical alteration of vestibular pathway in
      migraineurs who have never complained vertigo or postural imbalance. This finding
      supports the hypothesis of a vestibular-cerebellar dysfunction in migraineurs,
      particularly among those with aura.

PMID- 29658984
TI  - The SSAI fully supports the suspension of hydroxyethyl-starch solutions
      commissioned by the European Medicines Agency.

PMID- 29658985
TI  - Using rotational thromboelastometry clot firmness at 5 minutes (ROTEM(r) EXTEM
      A5) to predict massive transfusion and in-hospital mortality in trauma: a
      retrospective analysis of 1146 patients.
AB  - Viscoelastic assays such as TEG(r) and ROTEM(r) are increasingly used to guide
      transfusion of blood products. The EXTEM assay maximum clot firmness (MCF) is a
      ROTEM measure available after 25-29 min used to guide early decisions. EXTEM A10,
      the clot firmness at 10 min, is an accepted early surrogate, but investigators
      differ on whether A5, the clot firmness at 5 min, is acceptable. We re-examined
      this in a retrospective observational analysis of 1146 trauma patients in one
      centre who had ROTEM data recorded. A5 and A10 both correlated well with maximum
      clot firmness, with Pearson coefficients of r = 0.92 and r = 0.96, respectively.
      The correlations of A5, A10 and maximum clot firmness with requirement for
      massive transfusion were all similarly high, with c-stats of 0.87, 0.89 and 0.90,
      respectively. The correlations with mortality were also similar but weaker, with
      c-stats of 0.67, 0.69 and 0.69, respectively. Using a previously validated cut
      off of A5 < 35 mm to predict massive transfusion gave a sensitivity of 95%,
      specificity 83%, positive predictive value 9.3% and negative predictive value
      100%. Using a value of A5 < 29 mm, for a pragmatic positive predictive value of
      20%, gave a sensitivity of 67%, specificity 95% and negative predictive value
      99%. Whether aiming for a high sensitivity or a strong predictive value, A5 was
      non-inferior to A10 and actually missed fewer cases needing massive transfusion.
      A5 has similar utility to both A10 and maximum clot firmness as an early measure
      of clot firmness, and a low A5 value is strongly predictive of the need for
      massive transfusion.

PMID- 29658986
TI  - Natural fertility, infertility and the role of medically assisted reproduction:
      The knowledge amongst women of reproductive age in North Queensland.
AB  - BACKGROUND: The demand for medically assisted reproduction continues to increase,
      with more women encountering challenges with fertility. Due to misconceptions and
      gaps in knowledge, women are often unaware of the risks related to delayed
      childbearing. Lack of understanding of natural fertility, infertility and the
      role of medically assisted reproduction can lead to emotional suffering and
      changes in family plans. AIMS: To assess the understanding and knowledge that
      women of reproductive age in North Queensland have regarding natural fertility,
      infertility and the role of medically assisted reproduction. MATERIALS AND
      METHODS: Data were collected from 120 women (30 nurses, 30 teachers, 30
      university students and 30 Technical and Further Education students) via the
      distribution of a structured questionnaire. Participants were surveyed in person
      about their personal plans and opinions, knowledge about natural fertility,
      infertility and medically assisted reproduction, and their preferred source of
      information. RESULTS: Participants demonstrated suboptimal knowledge levels
      throughout all sections of the questionnaire, in particular when asked about
      medically assisted reproduction. When asked to identify their main source of
      information, 'friends and family' was the most popular choice. CONCLUSIONS:
      Results from this North Queensland study add to the existing international
      literature, highlighting the widespread nature of the problem. Without adequate
      understanding of natural fertility, the risks of infertility, and the role and
      limitations of medically assisted reproduction, women make uninformed decisions.
      Development of local reproductive health education programs need to be instigated
      in response.

PMID- 29658988
TI  - Merkel cell carcinoma in a patient treated with infliximab: Beware of the
      subcutaneous nodule.

PMID- 29658987
TI  - Does bilingualism increase brain or cognitive reserve in patients with temporal
      lobe epilepsy?
AB  - OBJECTIVE: Bilingual healthy adults have been shown to exhibit an advantage in
      executive functioning (EF) that is associated with microstructural changes in
      white matter (WM) networks. Patients with temporal lobe epilepsy (TLE) often show
      EF deficits that are associated with WM compromise. In this study, we investigate
      whether bilingualism can increase cognitive reserve and/or brain reserve in
      bilingual patients with TLE, mitigating EF impairment and WM compromise. METHODS:
      Diffusion tensor imaging was obtained in 19 bilingual and 26 monolingual patients
      with TLE, 12 bilingual healthy controls (HC), and 21 monolingual HC. Fractional
      anisotropy (FA) and mean diffusivity (MD) were calculated for the uncinate
      fasciculus (Unc) and cingulum (Cing), superior frontostriatal tract (SFS), and
      inferior frontostriatal tract (IFS). Measures of EF included Trail Making Test-B
      (TMT-B) and Delis-Kaplan Executive Function System Color-Word
      Inhibition/Switching. Analyses of covariance were conducted to compare FA and MD
      of the Unc, Cing, SFS, and IFS and EF performance across groups. RESULTS: In
      bilingual patients, FA was lower in the ipsilateral Cing and Unc compared to all
      other groups. For both patient groups, MD of the ipsilateral Unc was higher
      relative to HC. Despite more pronounced reductions in WM integrity, bilingual
      patients performed similarly to monolingual TLE and both HC groups on EF
      measures. By contrast, monolingual patients performed worse than HC on TMT-B. In
      addition, differences in group means between bilingual and monolingual patients
      on TMT-B approached significance when controlling for the extent of WM damage (P
      = .071; d = 0.62), suggesting a tendency toward higher performance for bilingual
      patients. SIGNIFICANCE: Despite poorer integrity of regional frontal lobe WM,
      bilingual patients performed similarly to monolingual patients and HC on EF
      measures. These findings align with studies suggesting that bilingualism may
      provide a protective factor for individuals with neurological disease,
      potentially through reorganization of EF networks that promote greater cognitive
      reserve.

PMID- 29658990
TI  - Finding an unfamiliar face in a line-up: Viewing multiple images of the target is
      beneficial on target-present trials but costly on target-absent trials.
AB  - When viewing unfamiliar faces, photographs of the same person often are perceived
      as belonging to different people and photographs of different people as belonging
      to the same person. Identity matching of unfamiliar faces is especially
      challenging when the photographs are of a person whose ethnicity differs from
      that of the observer. In contrast, matching is trivial when viewing familiar
      faces, regardless of race. Viewing multiple images of an own-race target identity
      improves accuracy on a line-up task when the target is known to be present
      (Dowsett et al., 2016, Q J Exp Psychol, 69, 1), suggesting that exposure to
      within-person variability in appearance is key to face learning. Across three
      experiments, we show that viewing multiple images of a target identity also
      improves accuracy for other-race faces on target-present trials. However, viewing
      multiple images decreases accuracy (i.e., increases false alarms) on target
      absent trials for both own- and other-race faces. We discuss the implications of
      our findings for models of face recognition and for forensic settings.

PMID- 29658989
TI  - The effectiveness of a group self-management education course for adults with
      poorly controlled epilepsy, SMILE (UK): A randomized controlled trial.
AB  - OBJECTIVE: Epilepsy is one of the most common neurological conditions affecting
      about 1% of adults. Up to 40% of people with epilepsy (PWE) report recurring
      seizures while on medication. And optimal functioning requires good self
      management. Our objective was to evaluate a group self-management education
      courses for people with epilepsy and drug-resistant seizures by means of a
      multicenter, pragmatic, parallel group, randomized controlled trial. METHODS: We
      recruited adults with epilepsy, having >=2 seizures in the prior 12 months, from
      specialist clinics. Consenting participants were randomized 1:1 to a group course
      or treatment as usual. The primary outcome measure was quality of life 12 months
      after randomization using Quality of Life 31-P (QOLIE-31-P). Secondary outcome
      measures were seizure frequency and recency, psychological distress, impact and
      stigma of epilepsy, self-mastery, medication adherence, and adverse effects.
      Analysis of outcomes followed the intention-to-treat principle using mixed
      effects regression models. RESULTS: We enrolled 404 participants (intervention: n
      = 205, control: n = 199) with 331 (82%) completing 12-month follow-up
      (intervention: n = 163, control: n = 168). Mean age was 41.7 years, ranging from
      16 to 85, 54% were female and 75% were white. From the intervention arm, 73.7%
      attended all or some of the course. At 12-month follow-up, there were no
      statistically significant differences between trial arms in QOLIE-31-P
      (intervention mean: 67.4, standard deviation [SD]: 13.5; control mean: 69.5, SD
      14.8) or in secondary outcome measures. SIGNIFICANCE: This is the first pragmatic
      trial of group education for people with poorly controlled epilepsy. Recruitment,
      course attendance, and follow-up rates were higher than expected. The results
      show that the primary outcome and quality of life did not differ between the
      trial arms after 12 months. We found a high prevalence of felt-stigma and
      psychological distress in this group of people with drug-resistant seizures. To
      address this, social and psychological interventions require evaluation, and may
      be necessary before or alongside self-management-education courses.

PMID- 29658991
TI  - Novel de novo synthesized phosphate carrier compound ABA-PEG20k-Pi20 suppresses
      collagenase production in Enterococcus faecalis and prevents colonic anastomotic
      leak in an experimental model.
AB  - BACKGROUND: Previous work has demonstrated that anastomotic leak can be caused by
      collagenolytic bacteria such as Enterococcus faecalis via an effect on wound
      collagen. In humans, E. faecalis is the organism cultured most commonly from a
      leaking anastomosis, and is not routinely eliminated by standard oral or
      intravenous antibiotics. Novel strategies are needed to contain the virulence of
      this pathogen when present on anastomotic tissues. METHODS: Polyphosphorylated
      polymer ABA-PEG20k-Pi20 was tested in mice for its ability to prevent anastomotic
      leak caused by collagenolytic E. faecalis. The study design included a distal
      colonic resection and anastomosis followed by introduction of E. faecalis to
      anastomotic tissues via enema. Mice were assigned randomly to receive either ABA
      PEG20-Pi20 or its unphosphorylated precursor ABA-PEG20k in their drinking water.
      The development of anastomotic leak was determined after the animals had been
      killed. RESULTS: Overnight incubation of two different E. faecalis collagenolytic
      strains with 2 mmol/l of ABA-PEG20k-Pi20 led to near complete inhibition of
      collagenase production (from 21 000 to 1000 and from 68 000 to 5000 units; P <
      0.001; 6 samples per group) without suppressing bacterial growth. In mice
      drinking 1 per cent ABA-PEG20k-Pi20, the phosphate concentration in the distal
      colonic mucosa increased twofold and leak rates decreased from eight of 15 to
      three of 15 animals (P < 0.001). In mice drinking ABA-PEG20k-Pi20, the percentage
      of collagenolytic colonies among E. faecalis populations present at anastomotic
      tissue sites was decreased by 6-4800-fold (P = 0.008; 5 animals). CONCLUSION:
      These data indicate that oral intake of ABA-PEG20k-Pi20 may be an effective agent
      to contain the virulence of E. faecalis and may prevent anastomotic leak caused
      by this organism. Clinical relevance Progress in understanding the pathogenesis
      of anastomotic leak continues to point to intestinal bacteria as key causative
      agents. The presence of pathogens such as Enterococcus faecalis that predominate
      on anastomotic tissues despite antibiotic use, coupled with their ability to
      produce collagenase, appears to alter the process of healing that leads to
      leakage. Further antibiotic administration may seem logical, but carries the
      unwanted risk of eliminating the normal microbiome, which functions competitively
      to exclude and suppress the virulence of pathogens such as E. faecalis.
      Therefore, non-antibiotic strategies that can suppress the production of
      collagenase by E. faecalis without affecting its growth, or potentially normal
      beneficial microbiota, may have unique advantages. The findings of this study
      demonstrate that drinking a phosphate-based polymer can achieve the goal of
      preventing anastomotic leak by suppressing collagenase production in E. faecalis
      without affecting its growth.

PMID- 29658992
TI  - Can mutation-mediated effects occurring early in development cause long-term
      seizure susceptibility in genetic generalized epilepsies?
AB  - Epilepsy has a strong genetic component, with an ever-increasing number of
      disease-causing genes being discovered. Most epilepsy-causing mutations are germ
      line and thus present from conception. These mutations are therefore well
      positioned to have a deleterious impact during early development. Here we review
      studies that investigate the role of genetic lesions within the early
      developmental window, specifically focusing on genetic generalized epilepsy
      (GGE). Literature on the potential pathogenic role of sub-mesoscopic structural
      changes in GGE is also reviewed. Evidence from rodent models of genetic epilepsy
      support the idea that functional and structural changes can occur in early
      development, leading to altered seizure susceptibility into adulthood. Both
      animal and human studies suggest that sub-mesoscopic structural changes occur in
      GGE. The existence of sub-mesoscopic structural changes prior to seizure onset
      may act as biomarkers of excitability in genetic epilepsies. We also propose that
      presymptomatic treatment may be essential for limiting the long-term consequences
      of disease-causing mutations in genetic epilepsies.

PMID- 29659000
TI  - Commentary on Bridging the Science-Practice Gap in Aging, Dementia, and Mental
      Health: Nursing Home Culture Change As an Exemplar.

PMID- 29658993
TI  - Does the Primary Care Behavioral Health Model Reduce Emergency Department Visits?
AB  - OBJECTIVE: To examine the impact of integrating behavioral health services using
      the primary care behavioral health (PCBH) model on emergency department (ED)
      utilization. DATA SOURCES: Utilization data from three Dane County, Wisconsin
      hospitals and four primary care clinics from 2003 to 2011. STUDY DESIGN: We used
      a retrospective, quasi-experimental, controlled, pre-post study design. Starting
      in 2007, two clinics began integrating behavioral health into their primary care
      practices with a third starting in 2010. A fourth, nonimplementing, community
      clinic served as control. Change in emergency department and primary care
      utilization (number of visits) for patients diagnosed with mood and anxiety
      disorders was the outcomes of interest. DATA COLLECTION: Retrospective data were
      obtained from electronic patient records from the three main area hospitals along
      with primary care data from participating clinics. PRINCIPAL FINDINGS: Following
      the introduction of the PCBH model, one clinic experienced a statistically
      significant (p < .01, 95 percent CI 6.3-16.3 percent), 11.3 percent decrease in
      the ratio of ED visits to primary care encounters, relative to a control site,
      but two other intervention clinics did not. CONCLUSIONS: The PCBH model may be
      associated with a reduction in ED utilization, but better-controlled studies are
      needed to confirm this result.

PMID- 29659002
TI  - Commentary on Apathy as a Model for Investigating Behavioral and Psychological
      Symptoms in Dementia.

PMID- 29659001
TI  - State of the Science: Apathy As a Model for Investigating Behavioral and
      Psychological Symptoms in Dementia.
AB  - Apathy is one of the most common and pervasive of the behavioral and
      psychological symptoms of dementia (BPSDs). Apathy has profound consequences for
      morbidity, mortality, and caregiver burden. Treatment of apathy has been hindered
      because of poor understanding of the mechanisms underlying this heterogeneous
      syndrome. Research has demonstrated that apathy is associated with disruption of
      the frontal-striatal system in individuals with neurodegenerative disease. As
      with other BPSDs, these neural mechanisms alone do not completely account for the
      syndrome; individual, caregiver, and environmental factors also contribute to
      apathy. In this article, we modify a current conceptual model of the factors
      contributing to BPSDs to examine determinants of apathy. This integrative model
      provides a more complete and theoretically informed understanding of apathy,
      allowing for greater insight into potential targets for research, intervention,
      and care. We end by proposing an agenda for moving the science of BPSDs in
      general, and apathy in particular, forward.

PMID- 29659003
TI  - State of Science: Bridging the Science-Practice Gap in Aging, Dementia and Mental
      Health.
AB  - The workforce available to care for older adults has not kept pace with the need.
      In response to workforce limitations and the growing complexity of healthcare,
      scientists have tested new models of care that redesign clinical practice. This
      article describes why new models of care in aging, dementia, and mental health
      diffuse inadequately into the healthcare systems and communities where they might
      benefit older adults. We review a general framework for the diffusion of
      innovations and highlight the importance of other features of innovations that
      deter or facilitate diffusion. Although scientists often focus on generating
      evidence-based innovations, end-users apply their own criteria to determine an
      innovation's value. In 1962, Rogers suggested six features of an innovation that
      facilitate or deter diffusion suggested: relative advantage, compatibility with
      the existing environment, ease or difficulty of implementation, trial-ability or
      ability to "test drive", adaptability, and observed effectiveness. We describe
      examples of models of care in aging, dementia and mental health that enjoy a
      modicum of diffusion into practice and place the features of these models in the
      context of deterrents and facilitators for diffusion. Developers of models of
      care in aging, dementia, and mental health typically fail to incorporate the
      complexities of health systems, the barriers to diffusion, and the role of
      emotion into design considerations of new models. We describe agile
      implementation as a strategy to facilitate the speed and scale of diffusion in
      the setting of complex adaptive systems, social networks, and dynamic
      macroenvironments.

PMID- 29659004
TI  - Commentary on State of the Science: Interprofessional Approaches to Aging,
      Dementia, and Mental Health.

PMID- 29659005
TI  - State of the Science of Neural Systems in Late-Life Depression: Impact on
      Clinical Presentation and Treatment Outcome.
AB  - Major depression in older adults, or late-life depression (LLD), is a common and
      debilitating psychiatric disorder that increases the risk of morbidity and
      mortality. Although the effects of LLD make it important to achieve a diagnosis
      and start treatment quickly, individuals with LLD are often inadequately or
      unsuccessfully treated. The latest treatment developments suggest that
      interventions targeting executive dysfunction and neuroticism, constructs
      associated with poor response to antidepressants in older adults, are successful
      in treating LLD. Specific behavioral interventions (computerized cognitive
      training, mindfulness meditation, aerobic exercise) appear to decrease depressive
      symptoms and ameliorate executive dysfunction and neuroticism, but we do not
      fully understand the mechanisms by which these treatments work. We review recent
      research on neural network changes underlying executive dysfunction and
      neuroticism in LLD and their association with clinical outcomes (e.g., treatment
      response, cognitive functioning).

PMID- 29659006
TI  - Health and Aging Policy Fellows: Dementia and Mental Health Policy to Improve
      Lives of Older Adults.
AB  - The Health and Aging Policy Fellows (HAPF) Program has, since its inception in
      2008, provided health policy training and mentorship for 113 gerontological
      professionals across a wide range of disciplines and stages of careers. The
      fellows' shared passion is the effective engagement of policy levers to improve
      the lives of older adults. This article briefly describes the HAPF Program and
      provides a sample of policies with which fellows have been engaged related to
      dementia and late-life mental health. Approximately 20% of the fellows have
      specifically addressed one of these areas during their fellowship year. This
      would be expected, given that 14% of older adults aged 71 and older have a
      diagnosis of dementia, and although new mental health diagnoses decline as adults
      age, mental health conditions remain prevalent. Thus, we conclude by describing
      opportunities for future advocacy and policy efforts in dementia and mental
      health in the areas of funding, translating science to practice,
      interprofessional education and innovative models of care for persons with these
      conditions.

PMID- 29659007
TI  - Challenges in Aging, Dementia, and Mental Health: New Knowledge and Energy to
      Inform Solutions.

PMID- 29659008
TI  - Commentary on Neural Systems in Late-Life Depression: Clinical Presentation and
      Treatment Outcome.

PMID- 29659009
TI  - State of the Science: Interprofessional Approaches to Aging, Dementia, and Mental
      Health.
AB  - Interprofessional education (IPE) is essential to develop the healthcare
      workforce of the future. Geriatrics healthcare professionals have long championed
      innovations in IPE and patient care, but there is increased urgency to address
      challenges in aging, dementia, and geriatric mental health in America. In 2010,
      the Partnership for Health in Aging multidisciplinary competencies and a related
      position statement in the Journal of the American Geriatrics Society addressed
      interdisciplinary team (IDT) training in geriatrics. The position statement
      reported that training in higher education, academic, and continuing education
      settings has not been sufficiently responsive to workforce needs. In recent
      years, health professions educators and health systems leaders have increasingly
      recognized that IPE should be integrally linked with, and performed within,
      emerging models of team-based, value-driven health care. In this way, IPE will
      align with learning healthcare systems' pursuit of the Quadruple Aim: improving
      patient experience, provider experience, and the health of populations, and
      reducing per capita health care costs. Backed by decades of developing effective
      team care models and the skill set needed to care for older adults with complex
      needs, geriatrics healthcare providers from multiple disciplines are uniquely
      positioned to lead learning healthcare systems in a new effort to develop,
      implement, and sustain IPE and practice models congruent with these Aims. We
      provide recommendations for health professions educators, healthcare systems
      leaders, and policymakers to realize the potential of IPE and interprofessional
      collaborative practice (IPCP) to improve the health of all Americans in aging,
      dementia, and mental health.

PMID- 29659010
TI  - Helping Consumers Make High-Value Health Care Choices: The Devil Is in the
      Details.

PMID- 29659011
TI  - Immune system augmentation via humanization using stem/progenitor cells and
      bioengineering in a breast cancer model study.
AB  - Despite significant advances, most current in vivo models fail to fully
      recapitulate the biological processes that occur in humans. Here we aimed to
      develop an advanced humanized model with features of an organ bone by providing
      different bone tissue cellular compartments including preosteoblasts, mesenchymal
      stem/stromal (MSCs), endothelial and hematopoietic cells in an engineered
      microenvironment. The bone compartment was generated by culturing the human MSCs,
      umbilical vein endothelial cells with gelatin methacryloyl hydrogels in the
      center of a melt-electrospun polycaprolactone tubular scaffolds, which were
      seeded with human preosteoblasts. The tissue engineered bone (TEB) was
      subcutaneously implanted into the NSG mice and formed a morphologically and
      functionally organ bone. Mice were further humanized through the tail vein
      injection of human cord blood derived CD34+ cells, which then populated in the
      mouse bone marrow, spleen and humanized TEB (hTEB). 11 weeks after CD34+
      transplantation, metastatic breast cancer cells (MDA-MB-231BO) were
      orthotopically injected. Cancer cell injection resulted in the formation of a
      primary tumor and metastasis to the hTEB and mouse organs. Less frequent
      metastasis and lower tumor burden were observed in hematochimeric mice,
      suggesting an immune-mediated response against the breast cancer cells. Overall,
      our results demonstrate the efficacy of tissue engineering approaches to study
      species-specific cancer-bone interactions. Further studies using genetically
      modified hematopoietic stem cells and bioengineered microenvironments will enable
      us to address the specific roles of signaling molecules regulating hematopoietic
      niches and cancer metastasis in vivo.

PMID- 29659012
TI  - Global burden of cutaneous melanoma attributable to ultraviolet radiation in
      2012.
AB  - Ultraviolet radiation (UVR) is a strong and ubiquitous risk factor for cutaneous
      melanoma, emitted naturally by the sun but also artificial sources. To shed light
      on the potential impact of interventions seeking to reduce exposure to UVR in
      both high and low risk populations, we quantified the number of cutaneous
      melanomas attributable to UVR worldwide. Population attributable fractions and
      numbers of new melanoma cases in adults due to ambient UVR were calculated by age
      and sex for 153 countries by comparing the current melanoma burden with
      historical data, i.e., the melanoma burden observed in a population with minimal
      exposure to UVR. Secondary analyses were performed using contemporary melanoma
      incidence rates in dark-skinned African populations with low UVR susceptibility
      as reference. Globally, an estimated 168,000 new melanoma cases were attributable
      to excess UVR in 2012, corresponding to 75.7% of all new melanoma cases and 1.2%
      of all new cancer cases. This burden was concentrated in very highly developed
      countries with 149,000 attributable cases and was most pronounced in Oceania,
      where 96% of all melanomas (representing 9.3% of the total cancer burden) were
      attributable to excess UVR. There would be approximately 151,000 fewer melanoma
      cases worldwide were incidence rates in every population equivalent to those
      observed in selected low-risk (dark-skinned, heavily pigmented) reference
      populations. These findings underline the need for public health action, an
      increasing awareness of melanoma and its risk factors, and the need to promote
      changes in behavior that decrease sun exposure at all ages.

PMID- 29659013
TI  - Dietary fat and fiber interact to uniquely modify global histone post
      translational epigenetic programming in a rat colon cancer progression model.
AB  - Dietary fermentable fiber generates short-chain fatty acids (SCFA), for example,
      butyrate, in the colonic lumen which serves as a chemoprotective histone
      deacetylase inhibitor and/or as an acetylation substrate for histone acetylases.
      In addition, n-3 polyunsaturated fatty acids (n-3 PUFA) in fish oil can affect
      the chromatin landscape by acting as ligands for tumor suppressive nuclear
      receptors. In an effort to gain insight into the global dimension of post
      translational modification of histones (including H3K4me3 and H3K9ac) and clarify
      the chemoprotective impact of dietary bioactive compounds on transcriptional
      control in a preclinical model of colon cancer, we generated high-resolution
      genome-wide RNA (RNA-Seq) and "chromatin-state" (H3K4me3-seq and H3K9ac-seq) maps
      for intestinal (epithelial colonocytes) crypts in rats treated with a colon
      carcinogen and fed diets containing bioactive (i) fish oil, (ii) fermentable
      fiber (a rich source of SCFA), (iii) a combination of fish oil plus pectin, or
      (iv) control, devoid of fish oil or pectin. In general, poor correlation was
      observed between differentially transcribed (DE) and enriched genes (DERs) at
      multiple epigenetic levels. The combinatorial diet (fish oil + pectin) uniquely
      affected transcriptional profiles in the intestinal epithelium, for example,
      upregulating lipid catabolism and beta-oxidation associated genes. These genes
      were linked to activated ligand-dependent nuclear receptors associated with n-3
      PUFA and were also correlated with the mitochondrial L-carnitine shuttle and the
      inhibition of lipogenesis. These findings demonstrate that the chemoprotective
      fish oil + pectin combination diet uniquely induces global histone state
      modifications linked to the expression of chemoprotective genes.

PMID- 29659015
TI  - Possible repurposing of pyrvinium pamoate for the treatment of mesothelioma: A
      pre-clinical assessment.
AB  - Malignant mesothelioma (MM) is a very aggressive asbestos-related cancer, whose
      incidence is increasing worldwide. Unfortunately, no effective therapies are
      currently available and the prognosis is extremely poor. Recently, the anti
      helminthic drug pyrvinium pamoate has attracted a strong interest for its anti
      cancer activity, which has been demonstrated in many cancer models. Considering
      the previously established inhibitory effect of pyrvinium pamoate on the Wnt/beta
      catenin pathway and given the important role of this pathway in MM, we
      investigated the potential anti-tumor activity of this drug in MM cell lines. We
      observed that pyrvinium pamoate significantly impairs MM cell proliferation,
      cloning efficiency, migration, and tumor spheroid formation. At the molecular
      level, our data show that pyrvinium pamoate down-regulates the expression of beta
      catenin and Wnt-regulates genes. Overall, our study suggests that the repurposing
      of pyrvinium pamoate for MM treatment could represent a new promising therapeutic
      approach.

PMID- 29659014
TI  - Single CpG hypermethylation, allele methylation errors, and decreased expression
      of multiple tumor suppressor genes in normal body cells of mutation-negative
      early-onset and high-risk breast cancer patients.
AB  - To evaluate the role of constitutive epigenetic changes in normal body cells of
      BRCA1/BRCA2-mutation negative patients, we have developed a deep bisulfite
      sequencing assay targeting the promoter regions of 8 tumor suppressor (TS) genes
      (BRCA1, BRCA2, RAD51C, ATM, PTEN, TP53, MLH1, RB1) and the estrogene receptor
      gene (ESR1), which plays a role in tumor progression. We analyzed blood samples
      of two breast cancer (BC) cohorts with early onset (EO) and high risk (HR) for a
      heterozygous mutation, respectively, along with age-matched controls. Methylation
      analysis of up to 50,000 individual DNA molecules per gene and sample allowed
      quantification of epimutations (alleles with >50% methylated CpGs), which are
      associated with epigenetic silencing. Compared to ESR1, which is representative
      for an average promoter, TS genes were characterized by a very low (< 1%) average
      methylation level and a very low mean epimutation rate (EMR; < 0.0001% to 0.1%).
      With exception of BRCA1, which showed an increased EMR in BC (0.31% vs. 0.06%),
      there was no significant difference between patients and controls. One of 36 HR
      BC patients exhibited a dramatically increased EMR (14.7%) in BRCA1, consistent
      with a disease-causing epimutation. Approximately one third (15 of 44) EO BC
      patients exhibited increased rates of single CpG methylation errors in multiple
      TS genes. Both EO and HR BC patients exhibited global underexpression of blood TS
      genes. We propose that epigenetic abnormalities in normal body cells are
      indicative of disturbed mechanisms for maintaining low methylation and
      appropriate expression levels and may be associated with an increased BC risk.

PMID- 29659016
TI  - Effects of attention during encoding on sex differences in object location
      memory.
AB  - Attention plays a key role in memory processes and has been widely studied in
      various memory tasks. The role of attention in sex differences in object location
      memory is not clearly understood. In the present study, two experiments involving
      186 participants and using an object array presented on paper were conducted to
      examine two encoding conditions: incidental and intentional. In each experiment,
      the participants were randomly assigned to divided versus full attention
      conditions. In the first experiment, which involved incidental encoding, women
      outperformed men in memorising location-exchanged objects in both the full and in
      the divided attention condition. In the second experiment, which involved
      intentional encoding, women outperformed men in memorising location-exchanged
      objects in the full attention condition, but not the divided attention condition.
      These findings deepen our knowledge regarding the role of attention in object
      location memory, specifically in terms of the conditions under which females have
      an advantage for detecting changes in an array of objects.

PMID- 29659017
TI  - Experiences of physical and relational victimization in children with ADHD: The
      role of social problems and aggression.
AB  - The social risk factors for physical and relational peer victimization were
      examined within a mixed-gender sample of children with and without attention
      deficit/hyperactivity disorder (ADHD). Participants were 124 children (ages 8-12
      years; 48% boys), with 47% exhibiting sub-clinical or clinical elevations in ADHD
      symptoms. ADHD and oppositional defiant disorder (ODD) symptom counts were
      assessed based on parent- and teacher-reports; parents rated children's social
      problems and teachers rated children's use of physical and relational aggression
      and experiences of physical and relational victimization. A multiple mediator
      model was used to test whether there were indirect effects of ADHD or ODD
      symptoms on physical and relational victimization through social problems,
      physical aggression, or relational aggression. At the bivariate level, ADHD and
      ODD symptoms were both significantly associated with higher rates of physical and
      relational victimization. In the mediational model, there were significant
      indirect effects of ADHD symptoms on relational victimization via social
      problems, of ODD on relational victimization via relational aggression, and of
      ODD symptoms on physical victimization via physical aggression. Results suggest
      that there are distinct risk factors implicated in the physical and relational
      victimization of youth with ADHD and that the co-occurrence of ODD symptoms is
      important to assess. Clinical implications for addressing victimization in
      children with ADHD are discussed.

PMID- 29659018
TI  - VMAT optimization with dynamic collimator rotation.
AB  - PURPOSE: Although collimator rotation is an optimization variable that can be
      exploited for dosimetric advantages, existing Volumetric Modulated Arc Therapy
      (VMAT) optimization uses a fixed collimator angle in each arc and only rotates
      the collimator between arcs. In this study, we develop a novel integrated
      optimization method for VMAT, accounting for dynamic collimator angles during the
      arc motion. METHODS: Direct Aperture Optimization (DAO) for Dynamic Collimator in
      VMAT (DC-VMAT) was achieved by adding to the existing dose fidelity objective an
      anisotropic total variation term for regulating the fluence smoothness, a binary
      variable for forming simple apertures, and a group sparsity term for controlling
      collimator rotation. The optimal collimator angle for each beam angle was
      selected using the Dijkstra's algorithm, where the node costs depend on the
      estimated fluence map at the current iteration and the edge costs account for the
      mechanical constraints of multi-leaf collimator (MLC). An alternating
      optimization strategy was implemented to solve the DAO and collimator angle
      selection (CAS). Feasibility of DC-VMAT using one full-arc with dynamic
      collimator rotation was tested on a phantom with two small spherical targets, a
      brain, a lung and a prostate cancer patient. The plan was compared against a
      static collimator VMAT (SC-VMAT) plan using three full arcs with 60 degrees of
      collimator angle separation in patient studies. RESULTS: With the same target
      coverage, DC-VMAT achieved 20.3% reduction of R50 in the phantom study, and
      reduced the average max and mean OAR dose by 4.49% and 2.53% of the prescription
      dose in patient studies, as compared with SC-VMAT. The collimator rotation co
      ordinated with the gantry rotation in DC-VMAT plans for deliverability. There
      were 13 beam angles in the single-arc DC-VMAT plan in patient studies that
      requires slower gantry rotation to accommodate multiple collimator angles.
      CONCLUSIONS: The novel DC-VMAT approach utilizes the dynamic collimator rotation
      during arc delivery. In doing so, DC-VMAT affords more sophisticated intensity
      modulation, alleviating the limitation previously imposed by the square beamlet
      from the MLC leaf thickness and achieves higher effective modulation resolution.
      Consequently, DC-VMAT with a single arc manages to achieve superior dosimetry
      than SC-VMAT with three full arcs.

PMID- 29659019
TI  - An enduring legacy: Dr. Alina Szczesniak's classification of food texture.

PMID- 29659020
TI  - Surgical management of chronic otitis secondary to craniomandibular osteopathy in
      three West Highland white terriers.
AB  - Three West Highland white terriers were presented for investigation of left-sided
      para-aural abscessation. CT revealed chronic otitis media with extensive osseous
      proliferation surrounding the horizontal and vertical ear canals contiguous with
      the expanded temporal bone, consistent with a unilateral variant of
      craniomandibular osteopathy. A left total ear canal ablation with lateral bulla
      osteotomy was performed in all dogs. An ultrasonic bone curette (Sonopet;
      Stryker) proved useful when removing the osseous proliferation in two dogs.
      Histopathological examination of the ear canals was consistent with
      craniomandibular osteopathy and the treatment led to resolution of the presenting
      clinical signs in all dogs. To our knowledge, this is the first report of
      craniomandibular osteopathy engulfing the external ear canal, presumably leading
      to chronic otitis media and para-aural abscess formation. This is also the first
      reported use of an ultrasonic bone curette in canine otic surgery.

PMID- 29659021
TI  - Absence of a moderating effect of parent health literacy on Early Head Start
      enrollment and dental use.
AB  - OBJECTIVES: To examine the moderating effect of parents' health literacy (HL) on
      the effectiveness of North Carolina Early Head Start (EHS) in improving
      children's dental use. METHODS: Parents of 479 children enrolled in EHS and 699
      Medicaid-matched parent-child dyads were interviewed at baseline when children
      were approximately 10 months old and 24 months later. We used in-person computer
      assisted, structured interviews to collect information on sociodemographic
      characteristics, dental use, and administer the Short Assessment of Health
      Literacy - Spanish and English (SAHL-S&E). This quasi-experimental study tested
      whether the interaction effect between EHS and parents' HL was associated with
      dental use. Logit (any use) and marginalized zero-inflated negative binomial
      count models (number of dental visits) included random effects to account for
      clustering and controlled for baseline dental use, dental need, survey language,
      and a propensity score covariate. RESULTS: Nineteen percent of parents in EHS had
      low literacy compared to 12 percent of parents in the non-EHS group (P < 0.01).
      The interaction term between EHS and parent's HL was not significant in the
      adjusted logit model (ratio of aORs 0.98, 95 percent CI: 0.43-2.20) or the
      adjusted count model (ratio of aRRs 0.88, 95 percent CI: 0.72-1.09). CONCLUSIONS:
      Parents in EHS had a higher prevalence of low HL compared to non-EHS parents.
      Parents' HL did not moderate the relationship between EHS and child dental use,
      suggesting that EHS results in similar improvements in dental use regardless of
      parent's HL levels.

PMID- 29659022
TI  - Transcription factor RD26 is a key regulator of metabolic reprogramming during
      dark-induced senescence.
AB  - Leaf senescence is a key process in plants that culminates in the degradation of
      cellular constituents and massive reprogramming of metabolism for the recovery of
      nutrients from aged leaves for their reuse in newly developing sinks. We used
      molecular-biological and metabolomics approaches to identify NAC transcription
      factor (TF) RD26 as an important regulator of metabolic reprogramming in
      Arabidopsis thaliana. RD26 directly activates CHLOROPLAST VESICULATION (CV),
      encoding a protein crucial for chloroplast protein degradation, concomitant with
      an enhanced protein loss in RD26 overexpressors during senescence, but a reduced
      decline of protein in rd26 knockout mutants. RD26 also directly activates LKR/SDH
      involved in lysine catabolism, and PES1 important for phytol degradation.
      Metabolic profiling revealed reduced gamma-aminobutyric acid (GABA) in RD26
      overexpressors, accompanied by the induction of respective catabolic genes.
      Degradation of lysine, phytol and GABA is instrumental for maintaining
      mitochondrial respiration in carbon-limiting conditions during senescence. RD26
      also supports the degradation of starch and the accumulation of mono- and
      disaccharides during senescence by directly enhancing the expression of AMY1,
      SFP1 and SWEET15 involved in carbohydrate metabolism and transport. Collectively,
      during senescence RD26 acts by controlling the expression of genes across the
      entire spectrum of the cellular degradation hierarchy.

PMID- 29659023
TI  - A dynamic model-based approach to motion and deformation tracking of prosthetic
      valves from biplane x-ray images.
AB  - PURPOSE: Transcatheter aortic valve replacement (TAVR) is a minimally invasive
      procedure in which a prosthetic heart valve is placed and expanded within a
      defective aortic valve. The device placement is commonly performed using two
      dimensional (2D) fluoroscopic imaging. Within this work, we propose a novel
      technique to track the motion and deformation of the prosthetic valve in three
      dimensions based on biplane fluoroscopic image sequences. METHODS: The tracking
      approach uses a parameterized point cloud model of the valve stent which can
      undergo rigid three-dimensional (3D) transformation and different modes of
      expansion. Rigid elements of the model are individually rotated and translated in
      three dimensions to approximate the motions of the stent. Tracking is performed
      using an iterative 2D-3D registration procedure which estimates the model
      parameters by minimizing the mean-squared image values at the positions of the
      forward-projected model points. Additionally, an initialization technique is
      proposed, which locates clusters of salient features to determine the initial
      position and orientation of the model. RESULTS: The proposed algorithms were
      evaluated based on simulations using a digital 4D CT phantom as well as
      experimentally acquired images of a prosthetic valve inside a chest phantom with
      anatomical background features. The target registration error was 0.12 +/- 0.04
      mm in the simulations and 0.64 +/- 0.09 mm in the experimental data. CONCLUSIONS:
      The proposed algorithm could be used to generate 3D visualization of the
      prosthetic valve from two projections. In combination with soft-tissue sensitive
      imaging techniques like transesophageal echocardiography, this technique could
      enable 3D image guidance during TAVR procedures.

PMID- 29659024
TI  - Predictors of Farmers' Market Shopping among People Receiving Supplemental
      Nutrition Assistance Program Benefits.
AB  - Promoting use of farmers' markets (FMs) is a promising community-level strategy
      to increase access to nutritious foods such as fruits and vegetables. Yet, FM
      shopping among people with Supplemental Nutrition Assistance Program (SNAP)
      benefits remains low. This research examined predictors of FM shopping among SNAP
      recipients living within 1 mile of a FM. A cross-sectional survey of SNAP
      participants (N = 270) was conducted in 2015 in Cleveland and East Cleveland, OH,
      USA. Multinomial regression and zero-truncated Poisson regression analyses were
      conducted to examine factors associated with FM shopping. Results indicate 48%
      reported shopping at a FM at least once in the past year, 26% had shopped at a FM
      before, but not in the last year, and 26% had never shopped at a FM. The
      multivariable analyses found awareness of FMs and a healthy food incentive
      program, and four dimensions of healthy food access are significantly associated
      with FM shopping among SNAP recipients. The food access dimensions included
      service delivery, spatial-temporal, personal, and social access. Findings
      highlight modifiable leverage points for improving the reach of FMs among low
      income populations.

PMID- 29659025
TI  - Synaptic depression induced by postsynaptic cAMP production in the Drosophila
      mushroom body calyx.
AB  - KEY POINTS: Synaptic potentiation in Drosophila is observed at cholinergic
      synapses between antennal lobe (AL) and mushroom body (MB) neurons in the adult
      brain; however, depression at the AL-MB synapses has not yet been identified. By
      ex vivo Ca2+ imaging in an isolated cultured Drosophila brain, we found novel
      activity-dependent depression at the AL-MB synapses. The degree of Ca2+ responses
      after repetitive AL stimulation is significantly reduced in the dendritic region
      of MB neurons (calyx) compared with those before AL stimulation, and this
      reduction of Ca2+ responses remains for at least 30 min. The expression of
      rutabaga, which encodes Ca2+ /calmodulin-dependent adenylyl cyclase, is essential
      in the MB neurons for the reduction of Ca2+ responses in the calyx. Our study
      reveals that elevation of cAMP production in the calyx during repetitive AL
      stimulation induces the depression at the AL-MB synapses. ABSTRACT: Synaptic
      plasticity has been studied to reveal the molecular and cellular mechanisms of
      associative and non-associative learning. The fruit fly Drosophila melanogaster
      can be used to identify the molecular mechanisms of synaptic plasticity because
      vast genetic information or tools are available. Here, by ex vivo Ca2+ imaging of
      an isolated cultured Drosophila brain, we examined the novel activity-dependent
      synaptic depression between the projection neurons of the antennal lobe (AL) and
      mushroom body (MB). Ex vivo Ca2+ imaging analysis revealed that electrical
      stimulation of AL elicits Ca2+ responses in the dendritic (calyx) and axonal
      (alpha lobe) regions of MB neurons, and the responses are reduced after
      repetitive AL stimulation. Since the cAMP signalling pathway plays an important
      role in synaptic plasticity in invertebrates and vertebrates, we examined whether
      the reduction of Ca2+ responses is also regulated by the cAMP signalling pathway.
      The expression of rutabaga (rut), which encodes Ca2+ /calmodulin-dependent
      adenylyl cyclase, was essential for the reduction of Ca2+ responses in the calyx
      and alpha lobe. Furthermore, imaging analysis using a fluorescence resonance
      energy transfer-based cAMP indicator revealed that the cAMP level increased in
      the wild-type calyx during repetitive AL stimulation, whereas it decreased in
      rut1 mutant flies with a loss-of-function mutation of rut. Thus, our study
      suggests that an increase in postsynaptic cAMP level during repetitive AL
      stimulation contributes to the attenuation of inputs at AL-MB synapses.

PMID- 29659027
TI  - Perioperative hematoma with subcutaneous ICD implantation: Impact of
      anticoagulation and antiplatelet therapies.
AB  - BACKGROUND: The safety of perioperative anticoagulation (AC) and antiplatelet
      (AP) therapy with subcutaneous implantable cardioverter-defibrillator (S-ICD)
      implantation is unknown. The purpose of this study was to identify the risk
      factors associated with hematoma complicating S-ICD implantation. METHODS:
      Records were retrospectively reviewed from 200 consecutive patients undergoing S
      ICD implantation at two academic medical centers. A hematoma was defined as a
      device site blood accumulation requiring surgical evacuation, extended hospital
      stay, or transfusion. RESULTS: Among 200 patients undergoing S-ICD implantation
      (age 49 +/- 17 years, 67% men), 10 patients (5%) had a hematoma, which required
      evacuation in six patients (3%). Warfarin was bridged or uninterrupted in 12 and
      13 patients, respectively (6% and 6.5%). Four of 12 patients with warfarin and
      bridging AC (33%) and two of 13 patients with uninterrupted warfarin (15%)
      developed a hematoma. Neither of the two patients with uninterrupted DOAC had a
      hematoma. No patients on interrupted AC without bridging (n = 26, 13 with
      warfarin, 13 with DOAC) developed a hematoma. A hematoma was also more likely
      with the use of clopidogrel (n = 4/10 vs 10/190, 40% vs 5.3%, P < 0.0001) in
      combination with aspirin in 12/14 patients. Any bridging AC (odds ratio [OR]
      10.3, 1.8-60.8, P = 0.01), clopidogrel (OR 10.0, 1.7-57.7, P = 0.01), and
      uninterrupted warfarin without bridging (OR 11.1, 1.7-74.3, P = 0.013) were
      independently associated with hematoma formation. CONCLUSION: AC and/or AP
      therapy with clopidogrel appears to increase the risk for hematoma following S
      ICD implantation. Interruption of AC without bridging should be considered when
      it is an acceptable risk to hold AC.

PMID- 29659026
TI  - beta1 subunit stabilises sodium channel Nav1.7 against mechanical stress.
AB  - KEY POINTS: The voltage-gated sodium channel Nav1.7 is a key player in neuronal
      excitability and pain signalling. In addition to voltage sensing, the channel is
      also modulated by mechanical stress. Using whole-cell patch-clamp experiments, we
      discovered that the sodium channel subunit beta1 is able to prevent the impact of
      mechanical stress on Nav1.7. An intramolecular disulfide bond of beta1 was
      identified to be essential for stabilisation of inactivation, but not activation,
      against mechanical stress using molecular dynamics simulations, homology
      modelling and site-directed mutagenesis. Our results highlight the role of
      segment 6 of domain IV in fast inactivation. We present a candidate mechanism for
      sodium channel stabilisation against mechanical stress, ensuring reliable channel
      functionality in living systems. ABSTRACT: Voltage-gated sodium channels are key
      players in neuronal excitability and pain signalling. Precise gating of these
      channels is crucial as even small functional alterations can lead to pathological
      phenotypes such as pain or heart failure. Mechanical stress has been shown to
      affect sodium channel activation and inactivation. This suggests that stabilising
      components are necessary to ensure precise channel gating in living organisms.
      Here, we show that mechanical shear stress affects voltage dependence of
      activation and fast inactivation of the Nav1.7 channel. Co-expression of the
      beta1 subunit, however, protects both gating modes of Nav1.7 against mechanical
      shear stress. Using molecular dynamics simulation, homology modelling and site
      directed mutagenesis, we identify an intramolecular disulfide bond of beta1
      (Cys21-Cys43) which is partially involved in this process: the beta1-C43A mutant
      prevents mechanical modulation of voltage dependence of activation, but not of
      fast inactivation. Our data emphasise the unique role of segment 6 of domain IV
      for sodium channel fast inactivation and confirm previous reports that the
      intracellular process of fast inactivation can be modified by interfering with
      the extracellular end of segment 6 of domain IV. Thus, our data suggest that
      physiological gating of Nav1.7 may be protected against mechanical stress in a
      living organism by assembly with the beta1 subunit.

PMID- 29659028
TI  - The Classroom Environment Questionnaire (CEQ): Development and preliminary
      structural validity.
AB  - BACKGROUND/AIM: Occupational therapists offer a unique perspective regarding the
      contribution of the environment to occupational performance. Therefore, a scale
      that measures the unique characteristics of the primary school classroom
      environment where children complete their daily schoolwork occupations is needed.
      The aim of this study was to develop and psychometrically evaluate a new teacher
      report questionnaire that measures a number of environmental characteristics of
      primary school classrooms. METHODS: Participants (N = 117) completed the
      Classroom Environment Questionnaire (CEQ), which utilises a 4-point Likert scale
      where teachers rate 51 environmental characteristics of their classroom. Teachers
      also rate the extent to which they believe the physical, social, temporal,
      institutional and cultural classroom environmental domains contribute to
      students' schoolwork performance using a 10-point scale. The structural validity
      of the CEQ was examined using principal component analysis (PCA). Inter-item
      correlations were examined using Pearson r correlations, while the internal
      consistency of the CEQ was assessed using Cronbach's alpha. RESULTS: PCA revealed
      the CEQ to be multidimensional, with 31 items loading onto nine viable factors,
      representing the unique nature of classroom environments. Based on the PCA
      results, 20 items were removed from the CEQ. Cronbach's alpha and correlation
      analysis indicated that most CEQ subsections had acceptable internal consistency
      (alpha range 0.70-0.82), with four subsections demonstrating a lower level of
      internal consistency (alpha range 0.55-0.69). CONCLUSION: Preliminary structural
      validity and internal consistency analysis findings confirm that the CEQ has
      potential to be a useful scale for professionals wishing to examine the unique
      characteristics of primary school classrooms that influence the occupational
      performance of students. Ongoing analyses will be undertaken to further explore
      the CEQ's validity and reliability.

PMID- 29659029
TI  - Circular-shaped microfluidic device to study the effect of shear stress on
      cellular orientation.
AB  - Understanding the effects of shear stress on mammalian cells is a crucial factor
      for understanding a number of biological processes and diseases. Here, we show
      the development of a circular-shaped microfluidic device for the facile
      generation of shear stress gradients. With this microfluidic device, the effect
      of shear stress on orientation of human umbilical vein endothelial cells was
      studied. This microfluidic device, which enables to control the alignment of
      human umbilical vein endothelial cells within a microchannel, can be a valuable
      tool to mimic blood vessels.

PMID- 29659030
TI  - Can night shift workers benefit from light exposure?

PMID- 29659031
TI  - Staff perceptions of borderline personality disorder and recovery: A Q-sort
      method approach.
AB  - OBJECTIVES: This study was the first to explore how staff that work with people
      diagnosed with borderline personality disorder (BPD) perceive recovery in this
      client group. These views are important because of the crucial role that staff
      play in the care of people with BPD, and the challenges that staff experience
      with these clients. DESIGN: A Q methodology design was used, containing 58
      statements about recovery. METHODS: Twenty-nine mental health staff sorted
      recovery statements according to perceived importance to recovery in BPD.
      RESULTS: There were two different viewpoints about recovery in BPD. A medically
      oriented group viewed coping with symptoms and behaviours specific to BPD as
      being most important to recovery, whereas participants who were more well-being
      oriented viewed achieving overall well-being that was universally valued
      regardless of diagnosis as more important. Both groups reported that engaging in
      socially valued activities such as work and education was not an important aspect
      of recovery and that people with BPD could be considered to have recovered
      despite continued impairments in everyday functioning. CONCLUSIONS: Staff
      perceptions of recovery in BPD can differ, which poses risks for consistent team
      working, a particularly important issue in this client group due to the
      relational difficulties associated with the diagnosis. Multidisciplinary teams
      working with people diagnosed with BPD therefore need to find a forum to promote
      a shared understanding of each patient's needs and support plans. We advocate
      that team formulation is a promising approach to achieve more consistent ways of
      working within teams. PRACTITIONER POINTS: Findings Multidisciplinary teams
      working with people with borderline personality disorder should use team
      formulations to create a shared understanding of individual patient's needs and
      goals for recovery, so they can deliver a consistent approach to care. Recovery
      questionnaires should be used to develop an understanding of a patient's
      individual recovery goals. Limitations Opportunity sampling was utilized in
      recruitment, and the sample was not representative of the general population of
      staff working with borderline personality disorder. Although views from a wide
      range of professions were sampled in this research, the views of psychiatrists
      were not represented.

PMID- 29659032
TI  - At, with and beyond risk: expectations of living with the possibility of future
      dementia.
AB  - Biomedical research aimed at the development of therapies for chronic and late
      onset conditions increasingly concentrates on the early treatment of symptom-less
      disease. This broad trend is evidenced in prominent shifts in contemporary
      dementia research. Revised diagnostic criteria and new approaches to clinical
      trials propose a focus on earlier stages of disease and prompt concerns about the
      implications of communicating test results associated with the risk of developing
      dementia when no effective treatments are available. This article examines
      expectations of the implications of learning test results related to dementia
      risk, based on focus group research conducted in the UK and Spain. It points to
      the extended social and temporal aspects of the dementia risk experience. Three
      key dimensions of this risk experience are elaborated: living 'at risk',
      represented in efforts to reduce risk and plan for the future; 'with risk',
      through vigilance towards cognitive health and earlier or prolonged contact with
      healthcare services; and finally, 'beyond risk' through a cessation of the self
      in its current social, legal and financial form. A virtual abstract of this paper
      can be viewed at: https://www.youtube.com/channel/UC_979cmCmR9rLrKuD7z0ycA.

PMID- 29659034
TI  - Embryo-fetal toxicity assessment of vonoprazan in rats and rabbits.
AB  - Vonoprazan is a new potassium-competitive acid blocker to treat acid-related
      diseases. However, its safety during pregnancy is unclear. The aim of the study
      was to investigate the potential reproductive toxicity on the embryo-fetal
      development of vonoprazan. Vonoprazan acetate was administered by intravenous
      injection to pregnant rats (0, 2, 6 and 20 mg kg-1 day-1 ) and rabbits (0, 1.2,
      3.6 and 12 mg kg-1 day-1 ) during the organogenetic period (gestation day 6-15
      [rats] and 6-18 [rabbits]). Maternal reproductive endpoints were evaluated,
      together with effects on fetal growth and morphological development. In rats, no
      treatment-related effects were found in the highest dose group (20 mg kg-1 ) and
      the maternal plasma exposure was >=50-fold the expected clinical human exposure.
      However, in rabbits, dose-related clinical signs (soft or liquid feces) occurred
      in the 12 mg kg-1 group, which was regarded as a maternal toxicity. Besides,
      decreased maternal weight gain also was considered as a minimal maternal
      toxicity. At 12 mg kg-1 , delayed fetal ossification was found as evidence of
      embryo-fetal growth retardation, which was related to decreased fetal and
      placental weights. There was no maternal and developmental toxicity in the 1.2
      and 3.6 mg kg-1 groups. Thus, the no-observed-adverse-effect levels of vonoprazan
      acetate in rabbits are considered 3.6 mg kg-1 day-1 , which produced plasma
      exposure that was about 18-fold human clinical exposure.

PMID- 29659033
TI  - GNA11 differentially mediates fibroblast growth factor 2- and vascular
      endothelial growth factor A-induced cellular responses in human fetoplacental
      endothelial cells.
AB  - KEY POINTS: Fetoplacental vascular growth is critical to fetal growth. Fibroblast
      growth factor 2 (FGF2) and vascular endothelial growth factor A (VEGFA) are two
      major regulators of fetoplacental vascular growth. G protein alpha subunit 11
      (GNA11) transmits signals from many external stimuli to the cellular interior and
      may mediate endothelial function. It is not known whether GNA11 mediates FGF2-
      and VEGFA-induced endothelial cell responses under physiological chronic low O2 .
      In the present study, we show that knockdown of GNA11 significantly decreases
      FGF2- and VEGFA-induced fetoplacental endothelial cell migration but not
      proliferation and permeability. Such decreases in endothelial migration are
      associated with increased phosphorylation of phospholipase C-beta3. The results
      of the present study suggest differential roles of GNA11 with respect to
      mediating FGF2- and VEGFA-induced fetoplacental endothelial function. ABSTRACT:
      During pregnancy, fetoplacental angiogenesis is dramatically increased in
      association with rapidly elevated blood flow. Any disruption of fetoplacental
      angiogenesis may lead to pregnancy complications such as intrauterine growth
      restriction. Fibroblast growth factor 2 (FGF2) and vascular endothelial growth
      factor A (VEGFA) are crucial regulators of fetoplacental angiogenesis. G protein
      alpha subunits q (GNAq) and 11 (GNA11) are two members of the Galphaq/11
      subfamily involved in mediating vascular growth and basal blood pressure.
      However, little is known about the roles of GNA11 alone with respect to mediating
      the FGF2- and VEGFA-induced fetoplacental endothelial function. Using a cell
      model of human umbilical cord vein endothelial cells cultured under physiological
      chronic low O2 (3% O2 ), we showed that GNA11 small interfering RNA (siRNA)
      dramatically inhibited (P < 0.05) FGF2- and VEGFA-stimulated fetoplacental
      endothelial migration (by ~36% and ~50%, respectively) but not proliferation and
      permeability. GNA11 siRNA also elevated (P < 0.05) FGF2- and VEGFA-induced
      phosphorylation of phospholipase C-beta3 (PLCbeta3) at S537 in a time-dependent
      fashion but not mitogen-activated protein kinase 3/1 (ERK1/2) and v-akt murine
      thymoma viral oncogene homologue 1 (AKT1). These data suggest that GNA11 mediates
      FGF2- and VEGFA-stimulated fetoplacental endothelial cell migration partially via
      altering the activation of PLCbeta3.

PMID- 29659035
TI  - Metabolomics-on-a-chip approach to study hepatotoxicity of DDT, permethrin and
      their mixtures.
AB  - Despite the diversity of studies on pesticide toxicities, there is a serious lack
      of information concerning the toxic effect of pesticides mixtures.
      Dichlorodiphenyl-trichloroethane (DDT) and permethrin (PMT) are among the most
      prevalent pesticides in the environment and have been the subject of several
      toxicological studies. However, there are no data on the toxicity of their
      mixtures. In this study, we used an approach combining cell culture in
      microfluidic biochips with gas chromatography-mass spectrometry metabolomics
      profiling to investigate the biomarkers of toxicity of DDT, PMT and their
      mixtures. All parameters observed indicated that no significant effect was
      observed in hepatocytes cultures exposed to low doses (15 MUm) of DDT and PMT.
      Conversely, combined low doses induce moderate oxidative stress and cell death.
      The toxic signature of high doses of pesticides (150 MUm) was illustrated by
      severe oxidative stress and cell mortality. Metabolomics profiling revealed that
      hepatocytes exposure to DDT150, PMT150 and DDT150 and PMT150 cause important
      modulation in intermediates of glutathione pathway and tricarboxylic acid cycle,
      amino acids and metabolites associated to hepatic necrosis and inflammation
      (alpha-ketoglutarate, arginine and 2-hydroxybutyrate). These changes were more
      striking in the combined group. Finally, DDT150 led to a significant increase of
      benzoate, decanoate, octanoate, palmitate, stearate and tetradecanoate, which
      illustrates the estrogen modulation. This study demonstrates the potential of
      metabolomics-on-a-chip approach to improve knowledge on the mode of action of
      pesticides.

PMID- 29659036
TI  - Therapeutic effect of thymoquinone against lead-induced testicular histological
      damage in male Wistar rats.
AB  - Lead (Pb) is a nonthreshold multi-targeted toxicant that causes alterations in
      different organs of the body, especially the gonads. This study was aimed to
      investigate the possible protective effect of thymoquinone (TQ), the major active
      ingredient of volatile oil of Nigella sativa seeds, against Pb-induced testicular
      histological damage. Adult male rats were randomised into four groups as follows:
      control group received no treatment, Pb group was exposed to 2000 ppm of Pb
      acetate in drinking water, Pb-TQ group was cotreated with Pb plus TQ (5
      mg/kg/day, per os) and TQ group receiving only TQ. All treatments were applied
      for five weeks. Results showed that Pb exposure produced morphological changes in
      the testis, especially degeneration of germinal epithelium, sloughing of germ
      cells into the lumen of seminiferous tubules and reduction in the number of
      luminal spermatozoa. Interestingly, coadministration of TQ to the metal-treated
      animals prevented the testicular adverse effects. In conclusion, our data
      indicate for the first time a remarkable protective effect of TQ against Pb
      induced testicular histopathological lesions in rat. On this basis, TQ deserves
      more consideration and further examination as a potential therapeutic option.

PMID- 29659038
TI  - Implementation Science: You've Come a Long Way, Baby.

PMID- 29659037
TI  - Optimization of drying process and pressurized liquid extraction for recovery of
      bioactive compounds from avocado peel by-product.
AB  - The aim of the present study was to optimize the extraction of phenolic compounds
      in avocado peel using pressurized liquid extraction (PLE) with GRAS solvents.
      Response surface methodology (RSM) based on Central Composite Design 22 model was
      used in order to optimize PLE conditions. Moreover, the effect of air drying
      temperature on the total polyphenol content (TPC) and individual phenolic
      compounds concentration were evaluated. The quantification of individual
      compounds was performed by HPLC-DAD-ESI-TOF-MS. The optimized extraction
      conditions were 200 degrees C as extraction temperature and 1:1 v/v as
      ethanol/water ratio. Regarding to the effect of drying, the highest TPC was
      obtained with a drying temperature of 85 degrees C. Forty seven phenolic
      compounds were quantified in the obtained extracts, showing that phenolic acids
      found to be the more stables compounds to drying process, while procyanidins were
      the more thermolabiles analytes. To our knowledge, this is the first available
      study in which phenolic compounds extraction was optimized using PLE and such
      amount of phenolic compounds was quantified in avocado peel. These results
      confirm that PLE represents a powerful tool to obtain avocado peel extracts with
      high concentration in bioactive compounds suitable for its use in the food,
      cosmetic or pharmaceutical sector.

PMID- 29659039
TI  - A meta-analysis of the relationships between body checking, body image avoidance,
      body image dissatisfaction, mood, and disordered eating.
AB  - OBJECTIVE: Body checking (BC) and body image avoidance (BIA) have been proposed
      as etiological and maintaining mechanisms for eating disorder (ED) pathology. To
      date, no comprehensive review summarizes the relationships of BC and BIA with ED
      pathology, body image dissatisfaction, or mood/affect. METHOD: Meta-analyses
      examined the relationships of BC and BIA with ED pathology, body image
      dissatisfaction, and mood/affect. Gender, publication status, and presence or
      absence of ED diagnoses were examined as potential moderators. RESULTS: Results
      showed strong relationships between BC and ED pathology (rho = 0.588) and BC and
      body image dissatisfaction (rho = 0.631) and a moderate relationship between BC
      and mood/affect (rho = 0.385). Similarly, results showed strong relationships
      between BIA and ED pathology (rho = 0.553) and BIA and body image dissatisfaction
      (rho = 0.543) and a moderate relationship between BIA and mood/affect (rho =
      0.392). Overall, limited evidence supported publication bias; however,
      publication bias may exist in the relationship between BIA and body image
      dissatisfaction in the literature. Subgroup moderator analyses suggested that
      gender moderates the strength of the relationships between BC and ED pathology,
      body image dissatisfaction, and mood/affect and between BIA and body image
      dissatisfaction. DISCUSSION: Results are consistent with cognitive-behavioral
      models of ED pathology that suggest BC and BIA are behavioral expressions of
      overvaluation of weight and shape. Notably, more published research has
      investigated BC than BIA. Future studies, incorporating methods such as meta
      analytic structural equation modeling, should examine these variables to further
      test cognitive-behavioral models of ED development and maintenance.

PMID- 29659040
TI  - The prognostic value of monosomal karyotype (MK) in higher-risk patients with
      myelodysplastic syndromes treated with 5-Azacitidine: A retrospective analysis of
      the Hellenic (Greek) Myelodysplastic syndromes Study Group.
AB  - In this study, we investigated the incidence and prognostic impact of monosomal
      karyotype (MK) in 405 higher-risk Myelodysplastic Syndromes (MDS) patients
      treated with 5-AZA. The MK was present in 66 out of 405 (16.3%) patients, most of
      whom had complex karyotype (CK). MK was strongly associated with CK and the
      cytogenetic risk defined according to IPSS-R, as well as with high-risk disease,
      according to IPSS (P = .029), IPSS-R (P < .001), and WPSS (P < .001)
      classification systems. The overall response rate (ORR) was not different between
      MK+ and MK- patients (46.6% vs. 46.2%). At 28 months median follow-up, the median
      duration of response was 11 months in the entire cohort, 9.5 months in MK+
      patients and 11 months in MK-patients (P = .024). The estimated median time to
      transformation to acute myeloid leukemia for MK+ patients was 17 months vs. 23
      months for MK- patients (P = .025). The estimated median OS for MK+ patients was
      12 months vs. 18 months for MK- patients (P < .001). Multivariate Cox regression
      analysis revealed that performance status (P < .001), IPSS-R (P < .001), and MK
      (P = .002) were independently associated with overall survival (OS). In a
      subgroup consisting of high and very-high risk patients according to IPSS-R, MK-
      patients showed better OS rates compared to MK+ patients (estimated median OS: 17
      months vs. 12 months, P = .002). In conclusion, we found that MK is associated
      with reduced OS in patients with higher-risk MDS treated with 5-AZA. Furthermore,
      we showed that in MDS with high or very-high IPSS-R risk score, MK can further
      distinguish patients with worse outcome.

PMID- 29659041
TI  - Association of added sugar intake and caries-related experiences among
      individuals of Mexican origin.
AB  - OBJECTIVE: Determine the association between key dental outcomes and added sugar
      intake using a survey instrument to assess added sugars, which was specifically
      tailored to immigrant and US-born adults of Mexican origin. METHODS: Hispanic
      adults of Mexican origin (n = 326; 36.2 +/- 12.1 years) completed a self
      administered survey to gather acculturation, self-reported dental experiences and
      self-care practices (eg brushing, flossing, pain, bleeding gums), and socio
      demographic information. The survey included a culturally tailored 22-item Added
      Sugar Intake Estimate (ASIE) that assessed added sugar intake from processed
      foods and sugar-sweetened beverages in a semiquantitative food frequency
      questionnaire format. Linear regression, 2-sample t test, and ANOVA were used to
      evaluate associations of demographic and dental outcomes with daily added sugar
      intake. RESULTS: Of the mean total daily added sugar intake (99.6 +/- 94.6 g),
      36.5 +/- 44.4 g was derived from sugar-containing foods and snacks, and 63.1 +/-
      68.2 g from beverages. Participants who reported greater added sugar intake were
      more likely to have reported the presence of a toothache in the preceding 12
      months, having been prescribed antibiotics for dental reasons, being less likely
      to floss daily, have reported eating or drinking within 1 hour before bed and
      have lower psychological acculturation (P < .05 for all). Results were comparable
      when assessing intake from sugar-containing foods/snacks and sugar-sweetened
      beverages. CONCLUSIONS: This study confirmed the association between added sugar
      intake and self-reported dental outcomes among adults of Mexican origin and
      points to an urgent need to improve dietary behaviours in this population.

PMID- 29659043
TI  - Utilizing Mechanistic Biomarkers in Treating Paracetamol Hepatotoxicity.

PMID- 29659042
TI  - Physician decision making in selection of second-line treatments in immune
      thrombocytopenia in children.
AB  - Immune thrombocytopenia (ITP) is an acquired autoimmune bleeding disorder which
      presents with isolated thrombocytopenia and risk of hemorrhage. While most
      children with ITP promptly recover with or without drug therapy, ITP is
      persistent or chronic in others. When needed, how to select second-line therapies
      is not clear. ICON1, conducted within the Pediatric ITP Consortium of North
      America (ICON), is a prospective, observational, longitudinal cohort study of 120
      children from 21 centers starting second-line treatments for ITP which examined
      treatment decisions. Treating physicians reported reasons for selecting
      therapies, ranking the top three. In a propensity weighted model, the most
      important factors were patient/parental preference (53%) and treatment-related
      factors: side effect profile (58%), long-term toxicity (54%), ease of
      administration (46%), possibility of remission (45%), and perceived efficacy
      (30%). Physician, health system, and clinical factors rarely influenced decision
      making. Patient/parent preferences were selected as reasons more often in chronic
      ITP (85.7%) than in newly diagnosed (0%) or persistent ITP (14.3%, P = .003).
      Splenectomy and rituximab were chosen for the possibility of inducing long-term
      remission (P < .001). Oral agents, such as eltrombopag and immunosuppressants,
      were chosen for ease of administration and expected adherence (P < .001).
      Physicians chose rituximab in patients with lower expected adherence (P = .017).
      Treatment choice showed some physician and treatment center bias. This study
      illustrates the complexity and many factors involved in decision-making in
      selecting second-line ITP treatments, given the absence of comparative trials. It
      highlights shared decision-making and the need for well-conducted, comparative
      effectiveness studies to allow for informed discussion between patients and
      clinicians.

PMID- 29659044
TI  - A case series describing causes of death in pregnant women with sickle cell
      disease in a low-resource setting.

PMID- 29659045
TI  - Surgical pulmonary embolectomy and catheter-directed thrombolysis for treatment
      of submassive pulmonary embolism.
AB  - BACKGROUND: Acute pulmonary embolism (PE) with preserved hemodynamics but right
      ventricular dysfunction, classified as submassive PE, carries a high risk of
      mortality. We report the results for patients who did not qualify for medical
      therapy and required treatment of submassive PE with surgical pulmonary
      embolectomy and catheter-directed thrombolysis (CDT). METHODS: Between October
      1999 and May 2015, 133 submassive PE patients underwent treatment with pulmonary
      embolectomy (71) and CDT (62). A multidisciplinary PE response team helped to
      determine the most appropriate treatment strategy on a case-by-case basis. The
      EkoSonic ultrasound-facilitated thrombolysis system (EKOS) was used for CDT,
      which was introduced in 2010. RESULTS: The mean age of submassive PE patients was
      57.3 years, which included 36.8% females. PE risk factors included previous deep
      venous thrombosis (46.6%), immobility (36.1%), recent surgery (30.8%), and cancer
      (22.6%), P < 0.05. The most common indication for advanced treatment was right
      ventricular strain (42.9%), P = 0.03. The frequency of surgical pulmonary
      embolectomy remained stable even after incorporating the EKOS procedure into our
      treatment algorithm, with statistically similar operative mortality. Bleeding was
      observed in six CDT patients and one pulmonary embolectomy patient (P < 0.05).
      Follow-up echocardiography was available for 61% of the overall cohort, of whom
      76.5% had no residual moderate or severe right ventricular dysfunction.
      CONCLUSIONS: Pulmonary embolectomy and CDT are important contemporary advanced
      treatment options for selected high-risk patients with submassive PE, who do not
      qualify for medical therapy.

PMID- 29659046
TI  - Polyethylene glycol treated allografts not tissue matched nor immunosuppressed
      rapidly repair sciatic nerve gaps, maintain neuromuscular functions, and restore
      voluntary behaviors in female rats.
AB  - Many publications report that ablations of segments of peripheral nerves produce
      the following unfortunate results: (1) Immediate loss of sensory signaling and
      motor control; (2) rapid Wallerian degeneration of severed distal axons within
      days; (3) muscle atrophy within weeks; (4) poor behavioral (functional) recovery
      after many months, if ever, by slowly-regenerating (~1mm/d) axon outgrowths from
      surviving proximal nerve stumps; and (5) Nerve allografts to repair gap injuries
      are rejected, often even if tissue matched and immunosuppressed. In contrast,
      using a female rat sciatic nerve model system, we report that neurorrhaphy of
      allografts plus a well-specified-sequence of solutions (one containing
      polyethylene glycol: PEG) successfully addresses each of these problems by: (a)
      Reestablishing axonal continuity/signaling within minutes by nonspecific ally PEG
      fusing (connecting) severed motor and sensory axons across each anastomosis; (b)
      preventing Wallerian degeneration by maintaining many distal segments of
      inappropriately-reconnected, PEG-fused axons that continuously activate nerve
      muscle junctions; (c) maintaining innervation of muscle fibers that undergo much
      less atrophy than otherwise-denervated muscle fibers; (d) inducing remarkable
      behavioral recovery to near-unoperated levels within days to weeks, almost
      certainly by CNS and PNS plasticities well-beyond what most neuroscientists
      currently imagine; and (e) preventing rejection of PEG-fused donor nerve
      allografts with no tissue matching or immunosuppression. Similar behavioral
      results are produced by PEG-fused autografts. All results for Negative Control
      allografts agree with current neuroscience data 1-5 given above. Hence, PEG
      fusion of allografts for repair of ablated peripheral nerve segments expand on
      previous observations in single-cut injuries, provoke reconsideration of some
      current neuroscience dogma, and further extend the potential of PEG-fusion in
      clinical practice.

PMID- 29659047
TI  - The changing face of adult posttransplant lymphoproliferative disorder: Changes
      in histology between 1999 and 2013.
AB  - Posttransplant lymphoproliferative disorder (PTLD) typically presents with either
      polymorphic or monomorphic histology. While both are the end result of
      immunosuppressive therapies, their origins are felt to be different with
      different prognoses and responsiveness to therapy, resulting in 2 different
      malignancies. We attempted to confirm reports suggesting that the relative
      frequency of these 2 histologies is shifting over time. We analyzed 3040 adult
      PTLD cases in the UNOS OPTN database from 1999 to 2013. Changes in PTLD cases
      over time were analyzed for histology, time from transplant to diagnosis, and
      patient EBV serostatus. We found that the relative proportion of polymorphic
      versus monomorphic histology has changed with an increase in the proportion of
      monomorphic cases with time (1999-2003, 54.9% vs. 45.1%; 2004-2008, 58.3% vs.
      41.7%; 2009-2013, 69.7% vs. 30.3%; P = <.001). The change is driven by a gradual
      increase in the number of monomorphic PTLD with a steady number of polymorphic
      PTLD. The change is most strongly seen in transplant recipients who were EBV
      serostatus positive at the time of transplant. Potential causes are changes in
      immunosuppressive regimens with increased tacrolimus use (P = .009) and increased
      survival among transplant patients leading to later occurrence of PTLD (P = .001)
      that have occurred during the time frame analyzed. As organ transplantation has
      evolved over time, PTLD has coevolved. These changes in histology have important
      implications regarding the origin and clinical management of PTLD.

PMID- 29659048
TI  - Time to plateau as a predictor of survival in newly diagnosed multiple myeloma.
AB  - Response rates in newly diagnosed multiple myeloma have improved dramatically
      with the introduction of highly effective novel therapies. However, survival in
      patients achieving optimal responses to initial treatment can vary significantly,
      and new prognostic indicators are required to improve risk stratification. We
      investigated the relationship between time to plateau (TPlat ) and survival in
      1099 newly diagnosed patients treated with novel agents at our institution from
      2005 to 2015. TPlat was defined as time from initiation of first-line therapy to
      best response to first-line therapy. The median TPlat was 4.9 months (0.7-58.6)
      and plateau duration was 1.8 years (0.2-11.0). Patients who required > 120 days
      to achieve a plateau had longer modified overall survival (mOS) and progression
      free survival (mPFS) calculated from a landmark of best response (P < .001 for
      both comparisons). Statistically significant improvement in mOS was retained in
      subgroup analysis based on age and whether patients received upfront autologous
      hematopoietic stem cell transplantation (ASCT) (P < .001 for all comparisons).
      Our results suggest that patients who respond more gradually to initial therapy
      (TPlat  > 120 days) experience longer survival compared to more rapid responders.
      Patients with a prolonged TPlat could represent an "ongoing responder" phenotype
      that portends a survival advantage independent of treatment with upfront ASCT,
      depth of response, and biologic markers such as ISS stage and cytogenetic risk.

PMID- 29659049
TI  - Clinical characteristics of peri-implant mucositis and peri-implantitis.
AB  - OBJECTIVES: To evaluate and correlate clinical parameters associated with peri
      implant diseases based on established case definitions. MATERIALS AND METHODS: A
      total of 75 patients exhibiting 269 implants (healthy: 77; peri-implant
      mucositis: 77; peri-implantitis: 115) were included in this observational study.
      Clinical parameters included bleeding on probing (BOP), probing depths (PDs), and
      suppuration (Supp). RESULTS: Healthy sites were associated with the absence of
      BOP, while mean BOP in peri-implant mucositis and peri-implantitis patients
      amounted to 20.83% and 71.33%, corresponding to 43% and 86% at the implant level
      (p < .001), respectively. Peri-implantitis patients exhibited significantly
      higher mean PD values (4.46 mm) when compared with the peri-implant mucositis
      group (2.70 mm, p < .001). Supp was limited to peri-implantitis cases and
      detected in 30.16% of the patients (implant level: 17.39%). The regression model
      revealed a significant linear association between the number of BOP-positive
      sites around the implant (minimum 0, maximum 6) and mean PD values at peri
      implant mucositis and peri-implantitis sites at both patient and implant levels.
      CONCLUSIONS: The clinical parameters investigated were shown to be associated
      with the severity of peri-implant diseases.

PMID- 29659050
TI  - Continuous electroencephalography predicts delayed cerebral ischemia after
      subarachnoid hemorrhage: A prospective study of diagnostic accuracy.
AB  - OBJECTIVE: Delayed cerebral ischemia (DCI) is a common, disabling complication of
      subarachnoid hemorrhage (SAH). Preventing DCI is a key focus of neurocritical
      care, but interventions carry risk and cannot be applied indiscriminately.
      Although retrospective studies have identified continuous electroencephalographic
      (cEEG) measures associated with DCI, no study has characterized the accuracy of
      cEEG with sufficient rigor to justify using it to triage patients to
      interventions or clinical trials. We therefore prospectively assessed the
      accuracy of cEEG for predicting DCI, following the Standards for Reporting
      Diagnostic Accuracy Studies. METHODS: We prospectively performed cEEG in
      nontraumatic, high-grade SAH patients at a single institution. The index test
      consisted of clinical neurophysiologists prospectively reporting prespecified EEG
      alarms: (1) decreasing relative alpha variability, (2) decreasing alpha-delta
      ratio, (3) worsening focal slowing, or (4) late appearing epileptiform
      abnormalities. The diagnostic reference standard was DCI determined by blinded,
      adjudicated review. Primary outcome measures were sensitivity and specificity of
      cEEG for subsequent DCI, determined by multistate survival analysis, adjusted for
      baseline risk. RESULTS: One hundred three of 227 consecutive patients were
      eligible and underwent cEEG monitoring (7.7-day mean duration). EEG alarms
      occurred in 96.2% of patients with and 19.6% without subsequent DCI (1.9-day
      median latency, interquartile range = 0.9-4.1). Among alarm subtypes, late onset
      epileptiform abnormalities had the highest predictive value. Prespecified EEG
      findings predicted DCI among patients with low (91% sensitivity, 83% specificity)
      and high (95% sensitivity, 77% specificity) baseline risk. INTERPRETATION: cEEG
      accurately predicts DCI following SAH and may help target therapies to patients
      at highest risk of secondary brain injury. Ann Neurol 2018;83:958-969.

PMID- 29659051
TI  - PSA-alpha-2-macroglobulin complex is enzymatically active in the serum of
      patients with advanced prostate cancer and can degrade circulating peptide
      hormones.
AB  - BACKGROUND: Prostate cancer cells produce high levels of the serine protease
      Prostate-Specific Antigen (PSA). PSA is enzymatically active in the tumor
      microenvironment but is presumed to be enzymatically inactive in the blood due to
      complex formation with serum protease inhibitors alpha-1-antichymotrypsin and
      alpha-2-macroglobulin (A2M). PSA-A2M complexes cannot be measured by standard
      ELISA assays and are also rapidly cleared from the circulation. Thus the exact
      magnitude of PSA production by prostate cancer cells is not easily measured. The
      PSA complexed to A2M is unable to cleave proteins but maintains the ability to
      cleave small peptide substrates. Thus, in advanced prostate cancer, sufficient
      PSA-A2M may be in circulation to effect total A2M levels, levels of cytokines
      bound to A2M and hydrolyze small circulating peptide hormones. METHODS: Total A2M
      levels in men with advanced prostate cancer and PSA levels above 1000 ng/mL were
      measured by ELISA and compared to controls. Additional ELISA assays were used to
      measure levels of IL-6 and TGF-beta which can bind to A2M. The ability of PSA-A2M
      complexes to hydrolyze protein and peptide substrates was analyzed +/- PSA
      inhibitor. Enzymatic activity of PSA-A2M in serum of men with high PSA levels was
      also assayed. RESULTS: Serum A2M levels are inversely correlated with PSA levels
      in men with advanced prostate cancer. Il-6 Levels are significantly elevated in
      men with PSA >1000 ng/mL compared to controls with PSA <0.1 ng/mL. PSA-A2M
      complex in serum of men with PSA levels >1000 ng/mL can hydrolyze small
      fluorescently labeled peptide substrates but not large proteins that are PSA
      substrates. PSA can hydrolyze small peptide hormones like PTHrP and osteocalcin.
      PSA complexed to A2M retains the ability to degrade PTHrP. CONCLUSIONS: In
      advanced prostate cancer with PSA levels >1000 ng/mL, sufficient PSA-A2M is
      present in circulation to produce enzymatic activity against circulating small
      peptide hormones. Sufficient PSA is produced in advanced prostate cancer to alter
      total A2M levels, which can potentially alter levels of a variety of growth
      factors such as IL-6, TGF-beta, basic FGF, and PDGF. Alterations in levels of
      these cytokines and proteolytic degradation of small peptide hormones may have
      profound effect on host-cancer interaction.

PMID- 29659052
TI  - Is the management of diabetes different in dialysis patients?
AB  - Diabetes is highly and increasingly prevalent in the dialysis population and
      negatively impacts both quality and quantity of life. Nevertheless, the best
      approach to these patients is still debatable. The question of whether the
      management of diabetes should be different in dialysis patients does not have a
      clear yes or no answer but is divided into too many sub-issues that should be
      carefully considered. In this review, lifestyle, cardiovascular risk, and
      hyperglycemia management are explored, emphasizing the possible pros and cons of
      a similar approach to diabetes in dialysis patients compared to the general
      population.

PMID- 29659053
TI  - Chiral syntheses of methyl (R)-2-Sulfanylcarboxylic esters and acids with optical
      purity determination using HPLC.
AB  - Accessible chiral syntheses of 3 types of (R)-2-sulfanylcarboxylic esters and
      acids were performed: (R)-2-sulfanylpropanoic (thiolactic) ester (53%, 98%ee) and
      acid (39%, 96%ee), (R)-2-sulfanylsucciinic diester (59%, 96%ee), and (R)-2
      mandelic ester (78%, 90%ee) and acid (59%, 96%ee). The present practical and
      robust method involves (i) clean SN 2 displacement of methanesulfonates of (S)-2
      hydroxyesters by using commercially available AcSK with tris(2-[2
      methoxyethoxy])ethylamine and (ii) sufficiently mild deacetylation. The optical
      purity was determined by the corresponding (2R,5R)-trans-thiazolidin-4-one and
      (2S,5R)-cis-thiazolidin-4-one derivatives based on accurate high-performance
      liquid chromatography analysis with high-resolution efficiency. Compared with the
      reported method utilizing AcSCs (generated from AcSH and CsCO3 ), the present
      method has several advantages, that is, the use of odorless AcCOSK reagent,
      reasonable reaction velocity, isolation procedure, and accurate, reliable optical
      purity determination. The use of accessible AcSK has advantages because of easy
      to-handle odorless and hygroscopic solid that can be used in a bench-top
      procedure. The Ti(OiPr)4 catalyst promoted smooth trans-cyclo-condensation to
      afford (2R,5R)-trans-thiazolidin-4-one formation of (R)-2-sulfanylcarboxylic
      esters with available N-(benzylidene)methylamine under neutral conditions without
      any racemization, whereas (2S,5R)-cis-thiazollidin-4-ones were obtained via cis
      cyclo-condensation and no catalysts. Direct high-performance liquid
      chromatography analysis of methyl (R)-mandelate was also performed; however, the
      resolution efficiency was inferior to that of the thaizolidin-4-one
      derivatizations.

PMID- 29659054
TI  - Tuning in C-nociceptors to reveal mechanisms in chronic neuropathic pain.
AB  - OBJECTIVE: Develop and validate a low-intensity sinusoidal electrical stimulation
      paradigm to preferentially activate C-fibers in human skin. METHODS: Sinusoidal
      transcutaneous stimulation (4Hz) was assessed psychophysically in healthy
      volunteers (n = 14) and neuropathic pain patients (n = 9). Pursuing laser Doppler
      imaging and single nociceptor recordings in vivo in humans (microneurography) and
      pigs confirmed the activation of "silent" C-nociceptors. Synchronized C-fiber
      compound action potentials were evoked in isolated human nerve fascicles in
      vitro. Live cell imaging of L4 dorsal root ganglia in anesthetized mice verified
      the recruitment of small-diameter neurons during transcutaneous 4-Hz stimulation
      of the hindpaw (0.4mA). RESULTS: Transcutaneous sinusoidal current (0.05-0.4mA,
      4Hz) activated "polymodal" C-fibers (50% at ~0.03mA) and "silent" nociceptors
      (50% at ~0.04mA), intensities substantially lower than that required with
      transcutaneous 1-ms rectangular pulses ("polymodal" ~3mA, "silent" ~50mA). The
      stimulation induced delayed burning (nonpulsating) pain and a pronounced axon
      reflex erythema, both indicative of C-nociceptor activation. Pain ratings to
      repetitive stimulation (1 minute, 4Hz) adapted in healthy volunteers by Numeric
      Rating Scale (NRS) -3 and nonpainful skin sites of neuropathic pain patients by
      NRS -0.5, whereas pain even increased in painful neuropathic skin by
      approximately NRS +2. INTERPRETATION: Sinusoidal electrical stimulation at 4Hz
      enables preferential activation of C-nociceptors in pig and human skin that
      accommodates during ongoing (1-minute) stimulation. Absence of such accommodation
      in neuropathic pain patients suggest axonal hyperexcitability that could be
      predictive of alterations in peripheral nociceptor encoding and offer a potential
      therapeutic entry point for topical analgesic treatment. Ann Neurol 2018;83:945
      957.

PMID- 29659055
TI  - Porphyrin Organic Framework Hollow Spheres and Their Applications in Lithium
      Sulfur Batteries.
AB  - Organic frameworks represent an emerging family of advanced materials that can be
      precisely controlled at the atomic level. However, morphology control of organic
      frameworks remains perplexing and difficult, strongly limiting the advantages of
      organic frameworks in multiple practical applications. Herein, porphyrin organic
      framework hollow spheres (POF-HSs) are fabricated by a template method as a proof
      of concept of organic frameworks with precisely controlled morphology. POF-HS
      exhibits explicit chemical structures of 2D POF and an expected hollow structure.
      The morphology of POF-HS is further regulated in terms of void size and shell
      thickness. Benefited from the polar chemical structures and the hollow spherical
      morphology, POF-HS sufficiently mitigates the shuttle of polysulfides by taking
      the dual effects of chemical adsorption and physical confinement and functions as
      a desirable host material for sulfur cathode to endow lithium-sulfur batteries
      with high capacity, long cycling life, and excellent rate performance. The
      accurate synthesis of POF-HSs demonstrates the highly controllable and versatile
      morphology of organic framework materials beyond precise integration of organic
      building blocks and represents infinite possibility of offering exotic organic
      frameworks for chemistry, sustainable energy, and material science.

PMID- 29659056
TI  - In honor of Professor Li-He Zhang on the occasion of his 80th birthday.

PMID- 29659059
TI  - High Electrical Conductivity of Single Metal-Organic Chains.
AB  - Molecular wires are essential components for future nanoscale electronics.
      However, the preparation of individual long conductive molecules is still a
      challenge. MMX metal-organic polymers are quasi-1D sequences of single halide
      atoms (X) bridging subunits with two metal ions (MM) connected by organic
      ligands. They are excellent electrical conductors as bulk macroscopic crystals
      and as nanoribbons. However, according to theoretical calculations, the
      electrical conductance found in the experiments should be even higher. Here, a
      novel and simple drop-casting procedure to isolate bundles of few to single MMX
      chains is demonstrated. Furthermore, an exponential dependence of the electrical
      resistance of one or two MMX chains as a function of their length that does not
      agree with predictions based on their theoretical band structure is reported.
      This dependence is attributed to strong Anderson localization originated by
      structural defects. Theoretical modeling confirms that the current is limited by
      structural defects, mainly vacancies of iodine atoms, through which the current
      is constrained to flow. Nevertheless, measurable electrical transport along
      distances beyond 250 nm surpasses that of all other molecular wires reported so
      far. This work places in perspective the role of defects in 1D wires and their
      importance for molecular electronics.

PMID- 29659058
TI  - Polyethylene glycol solutions rapidly restore and maintain axonal continuity,
      neuromuscular structures, and behaviors lost after sciatic nerve transections in
      female rats.
AB  - Complete severance of major peripheral mixed sensory-motor nerve proximally in a
      mammalian limb produces immediate loss of action potential conduction and
      voluntary behaviors mediated by the severed distal axonal segments. These severed
      distal segments undergo Wallerian degeneration within days. Denervated muscles
      atrophy within weeks. Slowly regenerating (~1 mm/day) outgrowths from surviving
      proximal stumps that often nonspecifically reinnervate denervated targets produce
      poor, if any, restoration of lost voluntary behaviors. In contrast, in this study
      using completely transected female rat sciatic axons as a model system, we
      provide extensive morphometric, immunohistochemical, electrophysiological, and
      behavioral data to show that these adverse outcomes are avoided by microsuturing
      closely apposed axonal cut ends (neurorrhaphy) and applying a sequence of well
      specified solutions, one of which contains polyethylene glycol (PEG). This "PEG
      fusion" procedure within minutes reestablishes axoplasmic and axolemmal
      continuity and signaling by nonspecifically fusing (connecting) closely apposed
      open ends of severed motor and/or sensory axons at the lesion site. These PEG
      fused axons continue to conduct action potentials and generate muscle action
      potentials and muscle twitches for months and do not undergo Wallerian
      degeneration. Continuously innervated muscle fibers undergo much less atrophy
      compared with denervated muscle fibers. Dramatic behavioral recovery to near
      unoperated levels occurs within days to weeks, almost certainly by activating
      many central nervous system and peripheral nervous system synaptic and other
      plasticities, some perhaps to a greater extent than most neuroscientists would
      expect. Negative control transections in which neurorrhaphy and all solutions
      except the PEG-containing solution are applied produce none of these remarkably
      fortuitous outcomes observed for PEG-fusion.

PMID- 29659060
TI  - Technical Note: A proposal of air ventilation system design criteria for a
      clinical room in a heavy-ion medical facility.
AB  - PURPOSE: An optimized air ventilation system design for a treatment room in Heavy
      ion Medical Facility is an important issue in the aspects of nuclear safety
      because the activated air produced in a treatment room can directly affect the
      medical staff and the general public in the radiation-free area. METHODS:
      Optimized design criteria of air ventilation system for a clinical room in 430
      MeV/u carbon ion beam medical accelerator facility was performed by using a
      combination of MCNPX2.7.0 and CINDER'90 codes. Effective dose rate and its
      accumulated effective dose by inhalation and residual gamma were calculated for a
      normal treatment scenario (2 min irradiation for one fraction) as a function of
      decay time. Natural doses around the site were measured before construction and
      used as reference data. RESULTS: With no air ventilation system, the maximum
      effective dose rate was about 3 MUSv/h (total dose of 90 mSv/y) and minimum 0.2
      MUSv/h (total dose of 6 mSv/y), which are over the legal limits for medical staff
      and for the general public. Although inhalation dose contribution was relatively
      small, it was considered seriously because of its long-lasting effects in the
      body. The integrated dose per year was 1.8 mSv/y in the radiation-free area with
      the 20-min rate of air ventilation system. CONCLUSION: An optimal air ventilation
      rate of 20 min is proposed for a clinical room, which also agrees with the best
      mechanical design value.

PMID- 29659061
TI  - Intermolecular interaction of fosinopril with bovine serum albumin (BSA): The
      multi-spectroscopic and computational investigation.
AB  - The intermolecular interaction of fosinopril, an angiotensin converting enzyme
      inhibitor with bovine serum albumin (BSA), has been investigated in physiological
      buffer (pH 7.4) by multi-spectroscopic methods and molecular docking technique.
      The results obtained from fluorescence and UV absorption spectroscopy revealed
      that the fluorescence quenching mechanism of BSA induced by fosinopril was
      mediated by the combined dynamic and static quenching, and the static quenching
      was dominant in this system. The binding constant, Kb , value was found to lie
      between 2.69 * 103 and 9.55 * 103  M-1 at experimental temperatures (293, 298,
      303, and 308 K), implying the low or intermediate binding affinity between
      fosinopril and BSA. Competitive binding experiments with site markers
      (phenylbutazone and diazepam) suggested that fosinopril preferentially bound to
      the site I in sub-domain IIA on BSA, as evidenced by molecular docking analysis.
      The negative sign for enthalpy change (DeltaH0 ) and entropy change (DeltaS0 )
      indicated that van der Waals force and hydrogen bonds played important roles in
      the fosinopril-BSA interaction, and 8-anilino-1-naphthalenesulfonate binding
      assay experiments offered evidence of the involvements of hydrophobic
      interactions. Moreover, spectroscopic results (synchronous fluorescence, 3
      dimensional fluorescence, and Fourier transform infrared spectroscopy) indicated
      a slight conformational change in BSA upon fosinopril interaction.

PMID- 29659062
TI  - Coacervation-Mediated Combinatorial Synthesis of Biomatrices for Stem Cell
      Culture and Directed Differentiation.
AB  - Combinatorial screening represents a promising strategy to discover biomaterials
      for tailored cell culture applications. Although libraries incorporating
      different biochemical cues have been investigated, few simultaneously
      recapitulate relevant biochemical, physical, and dynamic features of the
      extracellular matrix (ECM). Here, a noncovalent system based on liquid-liquid
      phase separation (coacervation) and gelation mediated by glycosaminoglycan (GAG)
      peptide interactions is reported. Multiple biomaterial libraries are generated
      using combinations of sulfated glycosaminoglycans and poly(ethylene glycol)
      conjugated peptides. Screening these biomaterials reveals preferred biomatrices
      for the attachment of six cell types, including primary mesenchymal stromal cells
      (MSCs) and primary neural precursor cells (NPCs). Incorporation of GAGs sustains
      the expansion of all tested cell types comparable to standard cell culture
      surfaces, while osteogenic differentiation of MSC and neuronal differentiation of
      NPC are promoted on chondroitin and heparan biomatrices, respectively. The
      presented noncovalent system provides a powerful tool for developing tissue
      specific ECM mimics.

PMID- 29659063
TI  - Parents' acceptance and their children's choice of pet for animal-assisted
      therapy (A.A.T.) in 3- to 12-year-old children in the dental operatory -A
      questionnaire-based pilot study.
AB  - AIM: To evaluate the parents' acceptance to therapy pets, child's most favoured
      pet, child's choice of soft toy as compared to live pet, and child's preference
      of his own pet versus therapy pet. METHODS: Sixty-two children of age groups 3-6
      year, 6-9 year, and 9-12 year were selected. The data from completed
      questionnaires were statistically analysed and subjected to z test, Chi-squared
      test with P value<0.05 considered as significant. RESULTS: The consent to the
      presence of pet was given by 41.47% parents of 9- to 12-year-old children, 34.15%
      parents of 6- to 9-year-old children and 24.39% parents of 3- to 6-year-old
      children. Children who chose dog as their preferred pet were 56.7%; those who
      chose cat as their preferred pet were 44%. A majority of 3-to 6-year-olds
      (63.15%) had dog & cat as their choice, while 6- to 9-year-olds (65.21%) & 9- to
      12-year-olds (40%) preferred dogs over all others. Dog was the favourite pet of
      46.8% children. More percentage of children wanted pet provided by clinic.
      CONCLUSIONS: Animal-Assisted Therapy (AAT) can prove to be a good behaviour
      management technique if more parents are made aware and informed about AAT; dog
      is one of the highly recommended pets for AAT, and therapy pet should be
      preferred over home pet.

PMID- 29659064
TI  - Beliefs and advice-seeking behaviours for fertility and pregnancy: a cross
      sectional study of a global sample.
AB  - BACKGROUND: Pregnancy can motivate individuals to adopt lifestyle behaviours that
      protect the health of their offspring. The aims of the present study were to
      explore men's and women's beliefs about lifestyle, fertility and pregnancy, as
      well as where they seek advice. METHODS: Participants (2185 women and 221 men,
      six unspecified) from 104 countries completed a questionnaire that explored their
      beliefs about what was important for a healthy pregnancy and their advice-seeking
      behaviours. Recruitment was via a Massive Open Online Course entitled 'Food as
      Medicine', with food, nutrient and health content. Comparisons of categorical
      data were performed using a chi-squared test (P = 0.05). RESULTS: Eating a
      variety of fruits and vegetables and not smoking (both 93.7%) were the most
      frequently and equally ranked in the top-five factors for a healthy pregnancy.
      Taking prenatal supplements (26.8%) was considered to be less important.
      Participants in Westernised countries ranked not smoking or drinking alcohol as
      being significantly more important than those in other countries. Overall,
      doctors (47.7%) were the most common source of fertility and pregnancy advice.
      Larger proportions of those aged <40 years used the Internet (<40 years 44.1%,
      >40 years 18.2% chi2 = 152.7, P < 0.01) and social media (<40 years 16.1%, >40
      years 3.6%; chi2 = 110.18, P < 0.01) for health information. CONCLUSIONS: There
      is disconnection between beliefs and actions regarding the lifestyle behaviours
      considered to be important for a healthy pregnancy, particularly nutrition.
      Pregnancy advice-seeking has evolved, with younger men and women utilising the
      Internet and social media. Health professionals must consider new communication
      strategies to deliver evidence-based lifestyle advice, particularly for younger
      men and women and where access to healthcare is limited.

PMID- 29659065
TI  - Comparing the reproducibility of commonly used magnetic resonance spectroscopy
      techniques to quantify cerebral glutathione.
AB  - BACKGROUND: Cerebral glutathione (GSH), a marker of oxidative stress, has been
      quantified in neurodegenerative diseases and psychiatric disorders using proton
      magnetic resonance spectroscopy (MRS). Using a reproducible MRS technique is
      important, as it minimizes the impact of measurement technique variability on the
      study results and ensures that other studies can replicate the results.
      HYPOTHESIS: We hypothesized that very short echo time (TE) acquisitions would
      have comparable reproducibility to a long TE MEGA-PRESS acquisition, and that the
      short TE PRESS acquisition would have the poorest reproducibility. STUDY TYPE:
      Prospective. SUBJECTS/PHANTOMS: Ten healthy adults were scanned during two
      visits, and six metabolite phantoms containing varying concentrations of GSH and
      metabolites with resonances that overlap with GSH were scanned once. FIELD
      STRENGTH/SEQUENCE: At 3T we acquired MRS data using four different sequences:
      PRESS, SPECIAL, PR-STEAM, and MEGA-PRESS. ASSESSMENT: Reproducibility of each MRS
      sequence across two visits was assessed. STATISTICAL TESTS: Mean coefficients of
      variation (CV) and mean absolute difference (AD) were used to assess
      reproducibility. Linear regressions were performed on data collected from
      phantoms to examine the agreement between known and quantified levels of GSH.
      RESULTS: Of the four techniques, PR-STEAM had the lowest mean CV and AD (5.4% and
      7.5%, respectively), implying excellent reproducibility, followed closely by
      PRESS (5.8% and 8.2%) and SPECIAL (8.0 and 10.1%), and finally by MEGA-PRESS
      (13.5% and 17.1%). Phantom data revealed excellent fits (R2 >= 0.98 or higher)
      using all methods. DATA CONCLUSION: Our data suggest that GSH can be quantified
      reproducibly without the use of spectral editing. LEVEL OF EVIDENCE: 2 Technical
      Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.

PMID- 29659066
TI  - A mass spectrometry based predictive strategy reveals ADAP1 is phosphorylated at
      tyrosine 364.
AB  - RATIONALE: The goal of this work was to identify phosphorylation sites within the
      amino acid sequence of human ADAP1. Using traditional mass spectrometry based
      techniques we were unable to produce interpretable spectra demonstrating
      modification by phosphorylation. This prompted us to employ a strategy in which
      phosphorylated peptides were first predicted using peptide mapping followed by
      targeted MS/MS acquisition. METHODS: ADAP1 was immunoprecipitated from extracts
      of HEK293 cells stably transfected with ADAP1 cDNA. Immunoprecipitated ADAP1 was
      digested with proteolytic enzymes and analyzed by LC/MS in MS1 mode by high
      resolution quadrupole time-of-flight mass spectrometry (QTOF-MS). Peptide
      molecular features were extracted using an untargeted data-mining algorithm.
      Extracted peptide neutral masses were matched against the ADAP1 amino acid
      sequence with phosphorylation included as a predicted modification. Peptides with
      predicted phosphorylation sites were analyzed by targeted LC/MS2 . Acquired MS2
      spectra were then analyzed using database search engines to confirm
      phosphorylation. Spectra of phosphorylated peptides were validated by manual
      interpretation. Further confirmation was performed by manipulating phospho
      peptide abundance using calf intestinal phosphatase (CIP) and the phorbol ester,
      phorbol 12-myristate 13-acetate (PMA). RESULTS: Of five predicted
      phosphopeptides, one, comprised of the sequence AVDRPMLPQEYAVEAHFK, was confirmed
      to be phosphorylated on a tyrosine at position 364. Pre-treatment of cells with
      PMA prior to immunoprecipitation increased the ratio of phosphorylated to
      unphosphorylated peptide as determined by area counts of extracted ion
      chromatograms (EIC). Addition of CIP to immunoprecipitation reactions eliminated
      the phosphorylated form. CONCLUSIONS: A novel phosphorylation site was identified
      at tyrosine 364. Phosphorylation at this site is increased by treatment with PMA.
      PMA promotes membrane translocation and activation of protein kinase C (PKC),
      indicating that tyrosine 364 is phosphorylated by a PKC-dependent mechanism.

PMID- 29659067
TI  - Computer-aided diagnosis of prostate cancer using a deep convolutional neural
      network from multiparametric MRI.
AB  - BACKGROUND: Deep learning is the most promising methodology for automatic
      computer-aided diagnosis of prostate cancer (PCa) with multiparametric MRI (mp
      MRI). PURPOSE: To develop an automatic approach based on deep convolutional
      neural network (DCNN) to classify PCa and noncancerous tissues (NC) with mp-MRI.
      STUDY TYPE: Retrospective. SUBJECTS: In all, 195 patients with localized PCa were
      collected from a PROSTATEx database. In total, 159/17/19 patients with 444/48/55
      observations (215/23/23 PCas and 229/25/32 NCs) were randomly selected for
      training/validation/testing, respectively. SEQUENCE: T2 -weighted, diffusion
      weighted, and apparent diffusion coefficient images. ASSESSMENT: A radiologist
      manually labeled the regions of interest of PCas and NCs and estimated the
      Prostate Imaging Reporting and Data System (PI-RADS) scores for each region.
      Inspired by VGG-Net, we designed a patch-based DCNN model to distinguish between
      PCa and NCs based on a combination of mp-MRI data. Additionally, an enhanced
      prediction method was used to improve the prediction accuracy. The performance of
      DCNN prediction was tested using a receiver operating characteristic (ROC) curve,
      and the area under the ROC curve (AUC), sensitivity, specificity, positive
      predictive value (PPV), and negative predictive value (NPV) were calculated.
      Moreover, the predicted result was compared with the PI-RADS score to evaluate
      its clinical value using decision curve analysis. STATISTICAL TEST: Two-sided
      Wilcoxon signed-rank test with statistical significance set at 0.05. RESULTS: The
      DCNN produced excellent diagnostic performance in distinguishing between PCa and
      NC for testing datasets with an AUC of 0.944 (95% confidence interval: 0.876
      0.994), sensitivity of 87.0%, specificity of 90.6%, PPV of 87.0%, and NPV of
      90.6%. The decision curve analysis revealed that the joint model of PI-RADS and
      DCNN provided additional net benefits compared with the DCNN model and the PI
      RADS scheme. DATA CONCLUSION: The proposed DCNN-based model with enhanced
      prediction yielded high performance in statistical analysis, suggesting that DCNN
      could be used in computer-aided diagnosis (CAD) for PCa classification. LEVEL OF
      EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;48:1570
      1577.

PMID- 29659068
TI  - Evolving standards of care in the age of cybertechnology.
AB  - Behavioral health professionals are making increased use of cybertechnology to
      deliver services to patients, communicate with patients, gather information about
      patients, and communicate with colleagues. The advent of cybertechnology -
      included the Internet, text (SMS), email, video, cloud storage of electronic
      records, and other forms of electronic communication and documentation - has
      introduced novel and unprecedented ethical and risk-management challenges. This
      article provides an overview of emerging issues related to informed consent;
      delivery of services; privacy, confidentiality, and privileged communication;
      boundary issues and dual relationships; documentation; and practitioners'
      relationships with colleagues. The author highlights new standards of care that
      are being incorporated into licensing statutes and regulations; professional
      codes of ethics; and practice guidelines adopted by the professions of
      psychiatry, psychology, mental health counseling, marriage and family therapy,
      and clinical social work.

PMID- 29659069
TI  - Regulating mobile mental health apps.
AB  - Mobile medical apps (MMAs) are a fast-growing category of software typically
      installed on personal smartphones and wearable devices. A subset of MMAs are
      aimed at helping consumers identify mental states and/or mental illnesses.
      Although this is a fledgling domain, there are already enough extant mental
      health MMAs both to suggest a typology and to detail some of the regulatory
      issues they pose. As to the former, the current generation of apps includes those
      that facilitate self-assessment or self-help, connect patients with online
      support groups, connect patients with therapists, or predict mental health
      issues. Regulatory concerns with these apps include their quality, safety, and
      data protection. Unfortunately, the regulatory frameworks that apply have failed
      to provide coherent risk-assessment models. As a result, prudent providers will
      need to progress with caution when it comes to recommending apps to patients or
      relying on app-generated data to guide treatment.

PMID- 29659070
TI  - Introduction to this Special Issue: The Internet, cybertechnology and the law.

PMID- 29659071
TI  - Traditional and new media's influence on suicidal behavior and contagion.
AB  - The role of nonfictional and fictional media in suicide contagion has been well
      established, ostensibly beginning with the publication of Goethe's The Sorrows of
      Young Werther in 1774. In recent decades, the emergence of several new forms of
      media (e.g. websites, social media, blogs, smartphone applications) has
      revolutionized the communication and social interaction paradigms. This article
      reviews "the Werther effect" (or suicide contagion related to media), special
      populations who are more influential or susceptible, current media reporting
      guidelines and their effectiveness, and the latest research on new media and its
      effect on suicide and suicide contagion. The aim is to update recommendations on
      how to mitigate the potential negative effects of both traditional and new media
      on suicidal behavior and suicide contagion.

PMID- 29659072
TI  - Characteristics and treatment of internet child pornography offenders.
AB  - In the realm of sexual offenses, there has been a decrease in hands-on offenses,
      but an increase in online offenses against children. The current issue is whether
      online and offline sexual offenders are alike or differ. This literature review
      investigates the differences among individuals who have committed child
      pornography offenses, individuals who have committed contact offenses against
      children, and individuals who have committed both. This review discusses the
      various typologies that have been proposed of those who have committed online
      offenses against children, the diagnostic implications of having committed child
      pornography offenses, and the current state of treatment and prevention of
      individuals who have committed online sex offenses against children. The studies
      examined were found from psychology databases, listserv links, and references of
      those collected articles. Only articles in English were included in the review.
      Overall, Internet child pornography offenders (ICPOs) tend to score significantly
      differently from contact offenders on various psychological measures. These
      findings may imply that ICPOs have different treatment needs than contact
      offenders.

PMID- 29659073
TI  - Online sexual activity involving webcams-An overview of existing literature and
      implications for sexual boundary violations of children and adolescents.
AB  - Despite the relevance of the Internet and its increasing use for sexual purposes,
      research into online sexual activity (OSA) involving webcams is limited. Aside
      from positive experiences, OSA may implicate violations of sexual boundaries,
      reaching from minor issues to serious forms of sexual abuse. To provide a basis
      for a classification of sexual boundary violations online and a conceptualization
      of preventive measures, a systematic review of the literature on OSA involving
      webcams was conducted, resulting in publications from four thematic categories:
      webcam use in common OSA, psychopathological phenomena, sex work, and crime and
      indecency (commercial sexual exploitation, trafficking, and sexual boundary
      violations). The discussion addresses the implications of different types of
      sexual boundary violation of children and adolescents on the Internet. The
      study's Internet findings could promote prevention and law enforcement strategies
      tailored to these types of offense as well as different target groups.

PMID- 29659074
TI  - Demographic, mental health, and offending characteristics of online child
      exploitation material offenders: A comparison with contact-only and dual sexual
      offenders.
AB  - Technological advances have dramatically increased the ability to access,
      distribute and produce child exploitation material (CEM) online, resulting in
      increased numbers of individuals being charged with CEM offences. This study
      examined the demographic, mental health, and offending characteristics of CEM
      offenders (n = 456) in comparison to child contact sexual offenders (n = 493) and
      offenders with a history of both CEM and contact offences (dual offenders, n =
      256). A robust data linkage methodology was employed to link records from
      statewide corrections services with policing and mental health records in
      Victoria, Australia. The results indicated that CEM offenders differed from both
      contact and dual offenders, and that the groups were primarily differentiated
      based on two factors: antisocial orientation and sexual deviance. CEM offenders
      demonstrated high rates of sexual deviance but low rates of antisociality,
      contact offenders exhibited the opposite pattern, and dual offenders had both
      high sexual deviance and antisociality. The findings suggest that existing sexual
      offender assessment and treatment frameworks are unlikely to be suitable for
      exclusive CEM offenders. The implications for future research are discussed.

PMID- 29659075
TI  - Glutathione transferases catalyze recycling of auto-toxic cyanogenic glucosides
      in sorghum.
AB  - Cyanogenic glucosides are nitrogen-containing specialized metabolites that
      provide chemical defense against herbivores and pathogens via the release of
      toxic hydrogen cyanide. It has been suggested that cyanogenic glucosides are also
      a store of nitrogen that can be remobilized for general metabolism via a
      previously unknown pathway. Here we reveal a recycling pathway for the cyanogenic
      glucoside dhurrin in sorghum (Sorghum bicolor) that avoids hydrogen cyanide
      formation. As demonstrated in vitro, the pathway proceeds via spontaneous
      formation of a dhurrin-derived glutathione conjugate, which undergoes reductive
      cleavage by glutathione transferases of the plant-specific lambda class (GSTLs)
      to produce p-hydroxyphenyl acetonitrile. This is further metabolized to p
      hydroxyphenylacetic acid and free ammonia by nitrilases, and then glucosylated to
      form p-glucosyloxyphenylacetic acid. Two of the four GSTLs in sorghum exhibited
      high stereospecific catalytic activity towards the glutathione conjugate, and
      form a subclade in a phylogenetic tree of GSTLs in higher plants. The expression
      of the corresponding two GSTLs co-localized with expression of the genes encoding
      the p-hydroxyphenyl acetonitrile-metabolizing nitrilases at the cellular level.
      The elucidation of this pathway places GSTs as key players in a remarkable scheme
      for metabolic plasticity allowing plants to reverse the resource flow between
      general and specialized metabolism in actively growing tissue.

PMID- 29659076
TI  - How to effectively design public health interventions: Implications from the
      interaction effects between socioeconomic status and health locus of control
      beliefs on healthy dietary behaviours among US adults.
AB  - This study investigated whether individuals with different socioeconomic status
      (SES) should be provided differently tailored health messages to promote healthy
      dietary behaviour (HDB). Prior research has suggested that people with different
      SESs tend to exhibit different types of beliefs about health, but it remains
      unclear how SES interacts with these beliefs to influence health outcomes. To
      better understand the differences in HDB between high- and low-SES populations
      and propose effective intervention strategies, we examined (i) how SES is
      associated with HDB, (ii) how internal health locus of control (HLC) and powerful
      others HLC are associated with HDB, and (iii) how SES interacts with internal and
      powerful others HLC to influence HDB. Using data from the Annenberg National
      Health Communication Survey, collected from 2005 to 2012 (N = 6,262) in the
      United States, hierarchical multiple regression analyses were conducted.
      Education level was found to be positively associated with HDB, while income
      level was not. Both internal and powerful others HLC beliefs were positively
      associated with HDB. The positive relationship between internal HLC and HDB
      strengthened as the level of education and income increased, whereas the positive
      relationship between powerful others HLC and HDB weakened as respondents'
      education level increased. These results suggest that the design and delivery of
      communication messages should be tailored to populations' specific SES and HLC
      beliefs for effective public health interventions. For example, messages
      enhancing internal HLC (e.g. providing specific skills and knowledge about health
      behaviours) might be more helpful for the richer and more-educated, while
      messages appealing to one's powerful others HLC beliefs (e.g. advice on health
      lifestyles given by well-known health professionals) might be more effective for
      less-educated people.

PMID- 29659077
TI  - Total choline quantification measured by 1H MR spectroscopy as early predictor of
      response after neoadjuvant treatment for locally advanced breast cancer: The
      impact of immunohistochemical status.
AB  - BACKGROUND: Validation of new biomarkers is essential for the early evaluation of
      neoadjuvant treatments. PURPOSE: To determine whether measurements of total
      choline (tCho) by 1H spectroscopy could predict morphological or pathological
      complete response (pCR) of neoadjuvant treatment and whether breast cancer
      subgroups are related to prediction accuracy. STUDY TYPE: Prospective,
      nonrandomized, monocentric, diagnostic study. POPULATION: Sixty patients were
      initially included with 39 women participating in the final cohort. FIELD
      STRENGTH/SEQUENCE: A 1.5T scanner was used for acquisition and MRS was performed
      using the syngo GRACE sequence. ASSESSMENT: MRS and MRI examinations were
      performed at baseline (TP1), 24-72 hours after first chemotherapy (TP2), after
      the end of anthracycline treatment (TP3), and MRI only after the end of taxane
      treatment (TP4). Early (EMR) and late (LMR) morphological response were defined
      as %DeltaDmax13 or %DeltaDmax14, respectively. Responders were patients with
      %DeltaDmax >30. Pathological complete response (pCR) patients achieved a residual
      cancer burden score of 0. STATISTICAL TESTS: T-test, receiver operating
      characteristic (ROC) curves, multiple regression, logistic regression, one-way
      analysis of variance (ANOVA) analysis were used for the analysis. RESULTS: At TP1
      there was a significant difference between response groups for tCho1 concerning
      EMR prediction (P = 0.05) and pCR (P < 0.05) and for Kep 1 (P = 0.03) concerning
      LMR prediction. At TP2, no modification of tCho and other parameters could
      predict response. At TP3, DeltatCho, DeltaDmax, and DeltaVol could predict LMR (P
      < 0.05 for all parameters), pCR (P < 0.05 for all parameters), and DeltaKtrans
      could predict only pCR (P = 0.04). Logistic regression at baseline showed the
      highest area under the curve (AUC) of 0.9 for prediction of pCR. The triple
      negative (TN) subgroup showed significantly higher tCho at baseline (P = 0.02)
      and higher DeltatCho levels at TP3 (P < 0.05). DATA CONCLUSION: Baseline
      measurements of tCho in combination with clinicopathological criteria could
      predict non-pCR with a high AUC. Furthermore, tCho quantification for prediction
      of pCR was more sensitive for TN tumors. LEVEL OF EVIDENCE: 1 Technical Efficacy:
      Stage 4 J. Magn. Reson. Imaging 2018;48:982-993.

PMID- 29659078
TI  - Mechanistic subtypes of focal right ventricular tachycardia.
AB  - Idiopathic sustained focal right ventricular tachycardia (VT) is most frequently
      due to outflow tract (OT) tachycardia. This arrhythmia is recognized by its
      characteristic ECG pattern and sensitivity to adenosine. However, there are other
      forms of idiopathic, focal sustained VT that originate from the right ventricle
      (RV), which are less well appreciated and easily overlooked. This review will
      identify the characteristic features and electrophysiologic properties of these
      forms of RV VT, including those originating from the tricuspid annulus, right
      ventricular papillary muscles, and moderator band as well as variants of classic
      RVOT tachycardia and those due to microreentry in the presence of preclinical
      disease. Recognition of these subtypes of focal RV tachycardia should facilitate
      targeted therapy.

PMID- 29659079
TI  - The impact of sex on disease phenotype and prognostic thresholds of anemia in
      myelodysplastic syndromes.

PMID- 29659080
TI  - Influence of fitness and age on the endothelial response to acute inflammation.
AB  - NEW FINDINGS: What is the central question of the study? What are the effects of
      age and fitness on the vascular response to acute inflammation in younger and
      older adults? What is the main finding and its importance? In older adults,
      cardiorespiratory fitness level has a differential impact on endothelial function
      after acute inflammation. Compared with older adults with low fitness, older,
      moderately fit adults have a greater decrease in endothelial function, similar to
      that of younger adults. These findings have important implications in support of
      the beneficial effects of higher cardiorespiratory fitness in maintaining
      vascular reactivity and the ability to respond to stressors. ABSTRACT:
      Inflammation is associated with greater risk of cardiovascular events and reduced
      vascular function with ageing. Higher cardiorespiratory fitness is associated
      with lower risk of cardiovascular events and better vascular function. We
      evaluated the role of fitness in the vascular response to acute inflammation in
      26 younger adults (YA) and 62 older adults (OA). We used an influenza vaccine to
      induce acute inflammation. Blood pressure, flow-mediated dilatation (FMD),
      augmentation index, carotid elastic modulus and inflammatory markers were
      measured before and 24 h after vaccination. Peak oxygen uptake was measured via a
      treadmill test. 'Fit' was defined as a peak oxygen uptake greater than the age-
      and sex-determined 50th percentile according to the American College of Sports
      Medicine. An interaction effect existed for the FMD response during acute
      inflammation (P < 0.05). The YA (low fit, from 11.5 +/- 1.8 to 9.2 +/- 1.3%;
      moderately fit, from 11.9 +/- 0.8 to 9.0 +/- 0.8%) and moderately fit OA (from
      7.5 +/- 1.0 to 3.9 +/- 0.8%) had similar reductions in FMD at 24 h (P < 0.05).
      Low-fit OA did not reduce FMD at 24 h (from 5.5 +/- 0.4 to 5.2 +/- 0.5%, P >
      0.05). The reduction in FMD in YA was similar between fitness groups (P > 0.05).
      All groups had similar reductions in mean arterial pressure and increases in
      inflammatory markers. The augmentation index and carotid elastic modulus did not
      change during acute inflammation. In conclusion, in OA, higher fitness is
      associated with a greater decrease in endothelial function during acute
      inflammation, and this response is similar to that of young adults. This suggests
      that moderately fit OA may maintain vascular reactivity in response to stress,
      indicating preserved vascular function in moderately fit versus low-fit OA.

PMID- 29659081
TI  - Gastrointestinal: Ulcerative colitis-associated duodenitis.

PMID- 29659082
TI  - Is hepatic peroxisome proliferator-activated receptor alpha essential for the
      metabolic effects of fibrates?

PMID- 29659083
TI  - Hepatobiliary and Pancreatic: Primary acinar cell carcinoma of the liver showing
      good response to chemotherapy.

PMID- 29659084
TI  - Hepatobiliary and Pancreatic: A case of pure squamous cell carcinoma of the
      gallbladder.

PMID- 29659085
TI  - Gastrointestinal: Recurrent acute pancreatitis with a large fluid collection:
      Pseudocyst or else?

PMID- 29659086
TI  - Gastrointestinal: An unusual cause of biliary colic: Biliary ascariasis.

PMID- 29659087
TI  - Robust spinal cord resting-state fMRI using independent component analysis-based
      nuisance regression noise reduction.
AB  - BACKGROUND: Physiological noise reduction plays a critical role in spinal cord
      (SC) resting-state fMRI (rsfMRI). PURPOSE: To reduce physiological noise and
      increase the robustness of SC rsfMRI by using an independent component analysis
      (ICA)-based nuisance regression (ICANR) method. STUDY TYPE: Retrospective.
      SUBJECTS: Ten healthy subjects (female/male = 4/6, age = 27 +/- 3 years, range 24
      34 years). FIELD STRENGTH/SEQUENCE: 3T/gradient-echo echo planar imaging (EPI).
      ASSESSMENT: We used three alternative methods (no regression [Nil], conventional
      region of interest [ROI]-based noise reduction method without ICA [ROI-based],
      and correction of structured noise using spatial independent component analysis
      [CORSICA]) to compare with the performance of ICANR. Reduction of the influence
      of physiological noise on the SC and the reproducibility of rsfMRI analysis after
      noise reduction were examined. The correlation coefficient (CC) was calculated to
      assess the influence of physiological noise. Reproducibility was calculated by
      intraclass correlation (ICC). STATISTICAL TESTS: Results from different methods
      were compared by one-way analysis of variance (ANOVA) with post-hoc analysis.
      RESULTS: No significant difference in cerebrospinal fluid (CSF) pulsation
      influence or tissue motion influence were found (P = 0.223 in CSF, P = 0.2461 in
      tissue motion) in the ROI-based (CSF: 0.122 +/- 0.020; tissue motion: 0.112 +/-
      0.015), and Nil (CSF: 0.134 +/- 0.026; tissue motion: 0.124 +/- 0.019). CORSICA
      showed a significantly stronger influence of CSF pulsation and tissue motion
      (CSF: 0.166 +/- 0.045, P = 0.048; tissue motion: 0.160 +/- 0.032, P = 0.048) than
      Nil. ICANR showed a significantly weaker influence of CSF pulsation and tissue
      motion (CSF: 0.076 +/- 0.007, P = 0.0003; tissue motion: 0.081 +/- 0.014, P =
      0.0182) than Nil. The ICC values in the Nil, ROI-based, CORSICA, and ICANR were
      0.669, 0.645, 0.561, and 0.766, respectively. DATA CONCLUSION: ICANR more
      effectively reduced physiological noise from both tissue motion and CSF pulsation
      than three alternative methods. ICANR increases the robustness of SC rsfMRI in
      comparison with the other three methods. LEVEL OF EVIDENCE: 2 Technical Efficacy:
      Stage 1 J. Magn. Reson. Imaging 2018;47:1421-1431.

PMID- 29659089
TI  - Recurrent aortic root pseudoaneurysm after transcatheter occlusion-A word of
      caution.
AB  - A 48-year-old male developed a recurrent aortic-root pseudoaneurysm after
      surgical repair for acute dissection. Although the initial closure of the
      pseudoaneurysm was successfully managed by transcatheter endovascular occlusion
      and coiling utilizing a hybrid transapical and transfemoral approach, the
      pseudoaneurysm was recanalized after 3 months and a third-time surgical repair
      was required. The potential risk for recurrence of pseudoaneurysms should be
      considered when applying endovascular occlusion devices to treat aortic root
      anatomy.

PMID- 29659088
TI  - Tunable Fano Resonance and Plasmon-Exciton Coupling in Single Au Nanotriangles on
      Monolayer WS2 at Room Temperature.
AB  - Tunable Fano resonances and plasmon-exciton coupling are demonstrated at room
      temperature in hybrid systems consisting of single plasmonic nanoparticles
      deposited on top of the transition metal dichalcogenide monolayers. By using
      single Au nanotriangles (AuNTs) on monolayer WS2 as model systems, Fano
      resonances are observed from the interference between a discrete exciton band of
      monolayer WS2 and a broadband plasmonic mode of single AuNTs. The Fano lineshape
      depends on the exciton binding energy and the localized surface plasmon resonance
      strength, which can be tuned by the dielectric constant of surrounding solvents
      and AuNT size, respectively. Moreover, a transition from weak to strong plasmon
      exciton coupling with Rabi splitting energies of 100-340 meV is observed by
      rationally changing the surrounding solvents. With their tunable plasmon-exciton
      interactions, the proposed WS2 -AuNT hybrids can open new pathways to develop
      active nanophotonic devices.

PMID- 29659090
TI  - Detection of intra-cardiac thrombi and congestive heart failure in cats using
      computed tomographic angiography.
AB  - Arterial thromboembolism is a life-threatening condition in cats most commonly
      secondary to cardiac disease. Echocardiography is the reference standard to
      evaluate for presence of a thrombus. In humans, computed tomographic (CT)
      angiography is becoming widely used to detect left atrial thrombi precluding the
      use of sedation. The purpose of this prospective, controlled, methods comparison
      pilot study was threefold: (1) describe new CT angiography protocol used in awake
      cats with cardiac disease and congestive heart failure; (2) determine accuracy of
      continuous and dynamic acquisition CT angiography to identify and characterize
      cardiac thrombi from spontaneous echocardiographic contrast using transthoracic
      echocardiography as our reference standard; (3) identify known negative
      prognostic factors and comorbidities of the thorax that CT angiography may
      provide that complement or supersede echocardiographic examination. Fourteen cats
      with heart disease were recruited; 7 with thrombi and 7 with spontaneous
      echocardiographic contrast. Echocardiography and awake CT angiography were
      performed using a microdose of contrast. Six of 7 thrombi were identified on CT
      angiography as filling defects by at least one reviewer within the left auricle
      (n = 6) and right heart (n = 1). Highest sensitivity (71.4%) was in continuous
      phase and highest specificity (85.7%) was in dynamic studies with fair to
      moderate interobserver agreement (0.38 and 0.44). CT angiography identified
      prognostic cardiac information (left atrial enlargement, congestive heart
      failure, arterial thromboembolism) and comorbidities (suspected idiopathic
      pulmonary fibrosis, asthma). This study indicates CT angiography can readily
      identify cardiac thrombi, important prognostic information and comorbidities, and
      can be safely performed in cats with cardiac disease and congestive heart
      failure.

PMID- 29659091
TI  - An argument against the implementation of an 'overarching universal addiction
      model' in alcohol and other drug treatment.

PMID- 29659092
TI  - Diffusion tensor imaging parameters in testes with nonobstructive azoospermia.
AB  - BACKGROUND: The development of noninvasive imaging parameters having the capacity
      to identify the population of men with nonobstructive azoospermia (NOA) where a
      successful sperm retrieval outcome is of great clinical significance.
      PURPOSE/HYPOTHESIS: To assess differences of apparent diffusion coefficient (ADC)
      and fractional anisotropy (FA) in NOA testes with impaired spermatogenesis and
      the possible association with the presence of spermatozoa after testicular sperm
      extraction (TESE). STUDY TYPE: Retrospective. POPULATION: Twenty NOA men (35
      testes) and 21 age-matched controls (36 testes). FIELD STRENGTH/SEQUENCE: 1.5T,
      T1 WI-SE T2 WI-FSE FS SS-EP-DTI. ASSESSMENTS: The MRI data were analyzed by two
      radiologists in consensus. The average ADC and FA of testicular parenchyma was
      measured. NOA testes were classified as NOA with higher Johnsen score (JS) >=8
      (group 1) and JS <8 (group 2). STATISTICAL TESTS: Parametric and nonparametric
      statistical tests were used to compare ADC and FA between NOA groups and normal
      testes (group 3) and to evaluate a possible association with the presence of
      spermatozoa after TESE. RESULTS: Differences in ADC were found between groups 1
      and 2 (P = 0.043) and groups 2 and 3 (P = 0.004), but not between groups 1 and 3
      (P = 0.418). Higher values of FA were found both in NOA testes with JS >=8 (P <
      0.001) and JS <8 (P < 0.001) compared to controls. ADC (P = 0.096) and FA (P =
      0.516) did not demonstrate differences in NOA testes with or without spermatozoa
      at TESE. DATA CONCLUSION: Both ADC and FA are increased in NOA testes compared to
      a normal population. ADC was proven to be a more useful diagnostic adjunct tool
      in the identification of the population of NOA men with foci of advanced
      spermatogenesis. However, DTI parameters were not predictive of sperm retrieval
      after TESE. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 3 J. Magn. Reson.
      Imaging 2018;47:1318-1325.

PMID- 29659093
TI  - Oral intake evaluation in patients following critical illness: an ICU cohort
      study.
AB  - Timely and adequate nutrition improves health outcomes for the critically ill
      patient. Despite clinical guidelines recommending early oral nutrition, survivors
      of critical illness experience significant nutritional deficits. This cohort
      study evaluates the oral nutrition intake in intensive care unit (ICU) patients
      who have experienced recent critical illness. The oral nutrition intake of a
      convenience sample of ICU patients post-critical illness was observed during a 1
      month period. Data pertaining to both the amount of oral nutrition intake and
      factors impacting optimal oral nutrition intake were collected and analysed.
      Inadequate oral intake was identified in 62% of the 79 patients assessed (n =
      49). This was noted early in the ICU stay, around day 1-2, for most of the
      patients. A significant proportion (25%) of patients remained in the hospital
      with poor oral intake that persisted beyond ICU day 5. Unsurprisingly, these were
      the patients who had longer ICU stays. Critical illness weakness was a factor in
      the assessment of poor oral intake. To conclude, patients who have experienced
      critical illness also experience suboptimal oral nutrition. The three key factors
      that were identified as impacting optimal oral nutrition were early removal of
      nasogastric tubes, critical illness weakness and poor appetite post-critical
      illness. Seven key recommendations are made based on this cohort study. These
      recommendations are related to patient assessment, monitoring, documentation and
      future guidelines. Future research opportunities are highlighted, including the
      investigation of strategies to improve the transition of patients' post-critical
      illness to oral nutrition.

PMID- 29659094
TI  - MERTK mutation update in inherited retinal diseases.
AB  - MER tyrosine kinase (MERTK) encodes a surface receptor localized at the apical
      membrane of the retinal pigment epithelium. It plays a critical role in
      photoreceptor outer segment internalization prior to phagocytosis. Mutations in
      MERTK have been associated with severe autosomal recessive retinal dystrophies in
      the RCS rat and in humans. We present here a comprehensive review of all reported
      MERTK disease causing variants with the associated phenotype. In addition, we
      provide further data and insights of a large cohort of 1,195 inherited retinal
      dystrophies (IRD) index cases applying state-of-the-art genotyping techniques and
      summarize current knowledge. A total of 79 variants have now been identified
      underlying rod-cone dystrophy and cone-rod dystrophy including 11 novel variants
      reported here. The mutation spectrum in MERTK includes 33 missense, 12 nonsense,
      12 splice defects, 12 small deletions, two small insertion-deletions, three small
      duplications, and two exonic and three gross deletions. Altogether, mutations in
      MERTK account for ~2% of IRD cases with a severe retinal phenotype. These data
      are important for current and future therapeutic trials including gene
      replacement therapy or cell-based therapy.

PMID- 29659095
TI  - Catalytic Direct-Type Addition Reactions of Alkylarenes with Imines and Alkenes.
AB  - Catalytic addition reactions of very weakly acidic nonactivated alkylarenes such
      as toluene and its derivatives were developed by using a strongly basic mixed
      catalyst system under mild reaction conditions. The addition reactions with
      imines and alkenes proceeded smoothly under proton-transfer conditions to afford
      the desired products in good to high yields, and high levels of regio- and
      stereoselectivity were achieved. It was also revealed that the asymmetric
      addition reaction of an alkylarene was possible.

PMID- 29659096
TI  - Liquid chromatography/mass spectrometry for the detection of ash tree metabolites
      following Emerald Ash Borer infestation.

PMID- 29659097
TI  - Regioselective Formation of (E)-beta-Vinylstannanes with a Topologically
      Controlled Molybdenum-Based Alkyne Hydrostannation Catalyst.
AB  - The regioselective formation of (E)-beta-vinylstannanes has been a long-standing
      challenge in transition-metal-catalyzed alkyne hydrostannation. Herein, we report
      a well-defined molybdenum-based system featuring two encumbering m-terphenyl
      isocyanides that reliably and efficiently delivers (E)-beta-vinylstannanes from a
      range of terminal and internal alkynes with high regioselectivity. The system is
      particularly effective for aryl alkynes and can discriminate between alkyl chains
      of low steric hindrance in unsymmetrically substituted dialkyl alkynes. Catalytic
      hydrostannation with this system is also characterized by an electronic effect
      that leads to a decrease in regioselectivity when electron-withdrawing groups are
      present on the alkyne substrate.

PMID- 29659098
TI  - The tangled duo of anaemia and transfusion travel together, that is the problem.

PMID- 29659100
TI  - 2D Porous TiO2 Single-Crystalline Nanostructure Demonstrating High Photo
      Electrochemical Water Splitting Performance.
AB  - Porous single crystals are promising candidates for solar fuel production owing
      to their long range charge diffusion length, structural coherence, and sufficient
      reactive sites. Here, a simple template-free method of growing a selectively
      branched, 2D anatase TiO2 porous single crystalline nanostructure (PSN) on
      fluorine-doped tin oxide substrate is demonstrated. An innovative ion exchange
      induced pore-forming process is designed to successfully create high porosity in
      the single-crystalline nanostructure with retention of excellent charge mobility
      and no detriment to crystal structure. PSN TiO2 film delivers a photocurrent of
      1.02 mA cm-2 at a very low potential of 0.4 V versus reversible hydrogen
      electrode (RHE) for photo-electrochemical water splitting, closing to the
      theoretical value of TiO2 (1.12 mA cm-2 ). Moreover, the current-potential curve
      featuring a small potential window from 0.1 to 0.4 V versus RHE under one-sun
      illumination has a near-ideal shape predicted by the Gartner Model, revealing
      that the charge separation and surface reaction on the PSN TiO2 photoanode are
      very efficient. The photo-electrochemical water splitting performance of the
      films indicates that the ion exchange-assisted synthesis strategy is effective in
      creating large surface area and single-crystalline porous photoelectrodes for
      efficient solar energy conversion.

PMID- 29659101
TI  - Lessons from Queensland's last-drinks legislation: The use of extended trading
      permits.
AB  - INTRODUCTION AND AIMS: The association between alcohol availability, alcohol
      consumption and, in turn, alcohol-related harms is well established. Policies to
      reduce alcohol-related harms focus on limiting accessibility through the
      regulation of the liquor industry, including trading hours. On 1 July 2016, the
      Queensland Government introduced legislation to reduce ordinary liquor trading
      hours, replacing 5 am closing times with 3 am cessation of liquor sales in
      designated entertainment precincts and 2 am cessation of sales across the rest of
      the state. However, the amendment was under-inclusive and did not apply to
      temporary extended trading permits, a provision of the Liquor Act 1992 allowing
      one-off variations in trading hours for special events. DESIGN AND METHODS: We
      use 24 months of data (1 January 2015 to 31 December 2016) from the Office of
      Liquor Gaming and Regulation to explore patterns of extended trading permit use
      across Queensland, pre- and post- 1 July 2016. RESULTS: We find that following
      the Amendment in 2016 there was also a distinct shift in the utilisation of
      temporary extended trading permits, with a 63% increase in approved permits
      between 2015 and 2016. Temporal clustering around key calendar events dissipated
      following 1 July 2016 with consistent concentration of permit utilisation over
      consecutive weeks. DISCUSSION AND CONCLUSIONS: Using temporary extended trading
      permits venue owners avoided earlier closing times and continued to operate until
      5 am. The findings provide lessons for future policy implementation by
      illustrating the capacity for under-inclusive legislation to result in the
      dilution of intended effects.

PMID- 29659102
TI  - Initial severity and antidepressant efficacy for anxiety disorders, obsessive
      compulsive disorder, and posttraumatic stress disorder: An individual patient
      data meta-analysis.
AB  - BACKGROUND: It has been suggested that antidepressant benefits are smaller for
      mild than severe depression. Because antidepressants are also used for anxiety
      disorders, obsessive-compulsive disorder (OCD), and posttraumatic stress disorder
      (PTSD), we examined the influence of severity for these disorders. METHODS: We
      used individual patient data of eight trials (3,430 participants) for generalized
      anxiety disorder (GAD); four trials (1,195 participants) for social anxiety
      disorder (SAD); four trials (1,132 participants) for OCD; three trials (1,071
      participants) for PTSD; and 10 trials (2,151 participants) for panic disorder
      (PD). Mixed-effects models were used to investigate an interaction between
      severity and treatment group. RESULTS: For GAD and PD, severity moderated
      antidepressant efficacy. The antidepressant-placebo difference was 1.4 (95% CI:
      0.4-2.5; SMD: 0.21) Hamilton Anxiety Rating Scale (HAM-A) points for participants
      with mild GAD (baseline HAM-A = 10), increasing to 4.0 (3.4-4.6; SMD: 0.45) or
      greater for severely ill participants (HAM-A >= 30). For PD, the difference was
      0.4 (0.3-0.6) panic attacks/2 weeks for participants with 10 panic attacks/2
      weeks at baseline, increasing to 4.7 (3.0-6.4) for participants with 40. For SAD,
      OCD, and PTSD, no interaction was found. Across severity levels, the differences
      were 16.1 (12.9-19.3; SMD: 0.59) Liebowitz Social Anxiety Scale points, 3.4 (2.5
      4.4, SMD: 0.39) Yale-Brown Obsessive-Compulsive Scale points, and 10.3 (6.9-13.6;
      SMD: 0.41) Clinician-Administered PTSD Scale points. CONCLUSIONS: Antidepressants
      are equally effective across severity levels for SAD, OCD, and PTSD. For GAD and
      PD, however, benefits are small at low severity, and the benefit-risk ratio may
      be unfavorable for these patients.

PMID- 29659103
TI  - Real-time lexical comprehension in young children learning American Sign
      Language.
AB  - When children interpret spoken language in real time, linguistic information
      drives rapid shifts in visual attention to objects in the visual world. This
      language-vision interaction can provide insights into children's developing
      efficiency in language comprehension. But how does language influence visual
      attention when the linguistic signal and the visual world are both processed via
      the visual channel? Here, we measured eye movements during real-time
      comprehension of a visual-manual language, American Sign Language (ASL), by 29
      native ASL-learning children (16-53 mos, 16 deaf, 13 hearing) and 16 fluent deaf
      adult signers. All signers showed evidence of rapid, incremental language
      comprehension, tending to initiate an eye movement before sign offset. Deaf and
      hearing ASL-learners showed similar gaze patterns, suggesting that the in-the
      moment dynamics of eye movements during ASL processing are shaped by the
      constraints of processing a visual language in real time and not by differential
      access to auditory information in day-to-day life. Finally, variation in
      children's ASL processing was positively correlated with age and vocabulary size.
      Thus, despite competition for attention within a single modality, the timing and
      accuracy of visual fixations during ASL comprehension reflect information
      processing skills that are important for language acquisition regardless of
      language modality.

PMID- 29659104
TI  - Photon Yield Enhancement of Red Fluorophores at Cryogenic Temperatures.
AB  - Single Molecule Localization Microscopy has become one of the most successful and
      widely applied methods of Super-resolution Fluorescence Microscopy. Its
      achievable resolution strongly depends on the number of detectable photons from a
      single molecule until photobleaching. By cooling a sample from room temperature
      down to liquid nitrogen temperatures, the photostability of dyes can be enhanced
      by more than 100 fold, which results in an improvement in localization precision
      greater than 10 times. Here, we investigate a variety of fluorescent dyes in the
      red spectral region, and we find an average photon yield between 3.5 ? 106 to 11
      ? 106 photons before bleaching at liquid nitrogen temperatures, corresponding to
      a theoretical localization precision around 0.1 nm.

PMID- 29659106
TI  - Individual treatment selection for patients with posttraumatic stress disorder.
AB  - BACKGROUND: Trauma-focused cognitive behavioral therapy (Tf-CBT) and eye movement
      desensitization and reprocessing (EMDR) are two highly effective treatment
      options for posttraumatic stress disorder (PTSD). Yet, on an individual level,
      PTSD patients vary substantially in treatment response. The aim of the paper is
      to test the application of a treatment selection method based on a personalized
      advantage index (PAI). METHOD: The study used clinical data for patients
      accessing treatment for PTSD in a primary care mental health service in the north
      of England. PTSD patients received either EMDR (N = 75) or Tf-CBT (N = 242). The
      Patient Health Questionnaire (PHQ-9) was used as an outcome measure for
      depressive symptoms associated with PTSD. Variables predicting differential
      treatment response were identified using an automated variable selection approach
      (genetic algorithm) and afterwards included in regression models, allowing the
      calculation of each patient's PAI. RESULTS: Age, employment status, gender, and
      functional impairment were identified as relevant variables for Tf-CBT. For EMDR,
      baseline depressive symptoms as well as prescribed antidepressant medication were
      selected as predictor variables. Fifty-six percent of the patients (n = 125) had
      a PAI equal or higher than one standard deviation. From those patients, 62 (50%)
      did not receive their model-predicted treatment and could have benefited from a
      treatment assignment based on the PAI. CONCLUSIONS: Using a PAI-based algorithm
      has the potential to improve clinical decision making and to enhance individual
      patient outcomes, although further replication is necessary before such an
      approach can be implemented in prospective studies.

PMID- 29659105
TI  - Lyso-DGTS lipid isolated from microalgae enhances PON1 activities in vitro and in
      vivo, increases PON1 penetration into macrophages and decreases cellular lipid
      accumulation.
AB  - High-density lipoprotein (HDL) plays an important role in preventing
      atherosclerosis. The antioxidant effect of HDL is mostly associated with
      paraoxonase 1 (PON1) activity. Increasing PON1 activity using nutrients might
      improve HDL function and quality and thus, decrease atherosclerotic risk. We
      previously isolated and identified a novel active compound, lyso-DGTS (C20:5,0)
      from Nannochloropsis sp. ethanol extract. In the present study, its effect on
      PON1 activities was examined and the mechanism by which the compound affects PON1
      activity was explored. Lyso-DGTS elevated recombinant PON1 (rePON1) lactonase and
      esterase activities in a dose- and time-responsive manner, and further stabilized
      and preserved rePON1 lactonase activity. Incubation of lyso-DGTS with human serum
      for 4 h at 37  degrees C also increased PON1 lactonase activity in a dose
      responsive manner. Using tryptophan-fluorescence-quenching assay, lyso-DGTS was
      found to interact with rePON1 spontaneously with negative free energy (DeltaG = 
      22.87 kJ mol-1 at 25  degrees C). Thermodynamic parameters and molecular modeling
      calculations showed that the main interaction of lyso-DGTS with the enzyme is
      through a hydrogen bond with supporting van der Waals interactions. Furthermore,
      lyso-DGTS significantly increased rePON1 influx into macrophages and prevented
      lipid accumulation in macrophages stimulated with oxidized low-density lipid dose
      dependently. In vivo supplementation of lyso-DGTS to the circulation of mice fed
      a high-fat diet via osmotic mini-pumps implanted subcutaneously significantly
      increased serum PON1 lactonase activity and decreased serum glucose
      concentrations to the level of mice fed a normal diet. Our findings suggest a
      beneficial effect of lyso-DGTS on increasing PON1 activity and thus, improving
      HDL quality and atherosclerotic risk factors. (c) 2018 BioFactors, 44(3):299-310,
      2018.

PMID- 29659107
TI  - Knowledge and practice of healthcare professionals relating to oral medicine use
      in swallowing-impaired patients: a scoping review.
AB  - OBJECTIVES: Swallowing impairment is a growing problem that affects 16% of the
      overall population and can significantly affect medicine-taking. However, little
      is known about the knowledge and practice of healthcare professionals (HCPs)
      relating to swallowing-impaired (SI) patients. The aim of this scoping review was
      to investigate the knowledge and practice of HCPs in supporting SI patients with
      their medicine-taking, to identify their reference sources, and to describe their
      training and information needs. METHOD: Databases searched included Scopus, Web
      of Science, Medline and Google Scholar from inception to August 2017. Qualitative
      and quantitative studies describing knowledge and practice of HCPs relating to
      medicine use in SI patients were included. KEY FINDINGS: The nine included
      studies, from an initial 142, involved nurses (nine studies), pharmacists (one
      study) and doctors (two studies) in hospitals or aged-care facilities. A
      knowledge deficit linked to lack of training was revealed, particularly with
      identification of modified-release dosage forms, medication that can/cannot be
      crushed, vehicle for safe dispersion, consequences of inappropriate modification,
      drug stability and legal aspects. Written information sources were named, but not
      used in practice. Pharmacists were the primary experts for consultation, and were
      involved in nurse education, and were members of multidisciplinary teams.
      CONCLUSIONS: Knowledge in nurses was inadequate, with practice indicating
      potentially serious medication-related errors. Additional training, either
      undergraduate or as continuing professional development, is recommended.
      Information to guide safe medicine modification practice should be accessible to
      all practitioners. Pharmacists could take the lead role in offering training to
      nurses.

PMID- 29659108
TI  - BEL1-LIKE HOMEODOMAIN 11 regulates chloroplast development and chlorophyll
      synthesis in tomato fruit.
AB  - Chloroplast development and chlorophyll(Chl)metabolism in unripe tomato
      contribute to the growth and quality of the fruit, however these mechanisms are
      poorly understood. In this study, we initially investigated seven homeobox
      containing transcription factors (TFs) with specific ripening-associated
      expression patterns using virus-induced gene silencing (VIGS) technology and
      found that inhibiting the expression of one of these TFs, BEL1-LIKE HOMEODOMAIN11
      (SlBEL11), significantly increased Chl levels in unripe tomato fruit. This
      enhanced Chl accumulation was further validated by generating stable RNA
      interference (RNAi) transgenic lines. RNA sequencing (RNA-seq) of RNAi-SlBEL11
      fruit at the mature green (MG) stage showed that 48 genes involved in Chl
      biosynthesis, photosynthesis and chloroplast development were significantly
      upregulated compared with the wild type (WT) fruit. Genomic global scanning for
      Homeobox TF binding sites combined with RNA-seq differential gene expression
      analysis showed that 22 of these 48 genes were potential target genes of SlBEL11
      protein. These genes included Chl biosynthesis-related genes encoding for
      protochlorophyllide reductase (POR), magnesium chelatase H subunit (CHLH) and
      chlorophyllide a oxygenase (CAO), and chloroplast development-related genes
      encoding for chlorophyll a/b binding protein (CAB), homeobox protein knotted 2
      (TKN2) and ARABIDOPSIS PSEUDO RESPONSE REGULATOR 2-LIKE (APRR2-like).
      Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation
      quantitative polymerase chain reaction (PCR) (ChIP-qPCR) assays were employed to
      verify that SlBEL11 protein could bind to the promoters for TKN2, CAB and POR.
      Taken together, our findings demonstrated that SlBEL11 plays an important role in
      chloroplast development and Chl synthesis in tomato fruit.

PMID- 29659109
TI  - A tool for assessment of heart failure prescribing quality: A systematic review
      and meta-analysis.
AB  - INTRODUCTION: Heart failure (HF) guidelines aim to standardise patient care.
      Internationally, prescribing practice in HF may deviate from guidelines and so a
      standardised tool is required to assess prescribing quality. A systematic review
      and meta-analysis were performed to identify a quantitative tool for measuring
      adherence to HF guidelines and its clinical implications. METHODS: Eleven
      electronic databases were searched to include studies reporting a comprehensive
      tool for measuring adherence to prescribing guidelines in HF patients aged >=18
      years. Qualitative studies or studies measuring prescription rates alone were
      excluded. Study quality was assessed using the Good ReseArch for Comparative
      Effectiveness Checklist. RESULTS: In total, 2455 studies were identified. Sixteen
      eligible full-text articles were included (n = 14 354 patients, mean age 69 +/- 8
      y). The Guideline Adherence Index (GAI), and its modified versions, was the most
      frequently cited tool (n = 13). Other tools identified were the Individualised
      Reconciled Evidence Recommendations, the Composite Heart Failure Performance, and
      the Heart Failure Scale. The meta-analysis included the GAI studies of good to
      high quality. The average GAI-3 was 62%. Compared to low GAI, high GAI patients
      had lower mortality rate (7.6% vs 33.9%) and lower rehospitalisation rates (23.5%
      vs 24.5%); both P <= .05. High GAI was associated with reduced risk of mortality
      (hazard ratio = 0.29, 95% confidence interval, 0.06-0.51) and rehospitalisation
      (hazard ratio = 0.64, 95% confidence interval, 0.41-1.00). No tool was used to
      improve prescribing quality. CONCLUSION: The GAI is the most frequently used tool
      to assess guideline adherence in HF. High GAI is associated with improved HF
      outcomes.

PMID- 29659110
TI  - Rapid Aqueous Late-Stage Radiolabelling of [GaF3 (BnMe2 -tacn)] by 18 F/19 F
      Isotopic Exchange: Towards New PET Imaging Probes.
AB  - A simple and rapid method for 18 F radiolabelling of [GaF3 (BnMe2 -tacn)] by 18
      F/19 F isotopic exchange is described. The use of MeCN/H2 O or EtOH/H2 O (75:25)
      and aqueous [18 F]F- (up to 200 MBq) with heating (80  degrees C, 10 min) gave
      66+/-4 % 18 F incorporation at a concentration of 268 nm, and 37+/-5 % 18 F
      incorporation at even lower concentration (27 nm), without the need for a Lewis
      acid promoter. A solid-phase extraction method was established to give [Ga18 F19
      F2 (BnMe2 -tacn)] in 99 % radiochemical purity in an EtOH/H2 O mixture.

PMID- 29659111
TI  - Trends in body mass index and obesity prevalence in Western Australian adults,
      2002 to 2015.
AB  - ISSUE ADDRESSED: Continued increases in overweight and obesity across most parts
      of the world in recent decades have seen maintaining or reaching a healthy weight
      become a major public health priority. This study reports on body mass index
      (BMI) and obesity prevalence trends in Western Australian adults between 2002 and
      2015. METHODS: Self-reported height and weight were collected from Western
      Australian adults (16+ years) via 81 867 computer-assisted telephone interviews
      conducted between 2002 and 2015 as part of the WA Health and Wellbeing
      Surveillance System. Linear and quadratic trends in annual mean BMI and obesity
      prevalence estimates were generated from self-report data. These trends were
      subject to sequential sum of squares analysis to examine whether annual increases
      in mean BMI and obesity prevalence estimates diminished or were maintained over
      the 2002 to 2015 period. RESULTS: The analyses showed a preference for a
      quadratic model (with plots suggesting diminishing increases between 2002 and
      2015) in mean BMI for males, 25- to 64-year-olds and across all adults, and in
      obesity prevalence estimates across all adults. CONCLUSIONS: The results suggest
      the rate at which mean BMI and obesity prevalence are increasing may be slowing
      overall and within specific groups in WA. SO WHAT?: The findings are potentially
      a positive news story for health in Western Australia. Even so, 2-thirds of the
      population are overweight or obese and there remains a strong need for sustained
      obesity prevention action.

PMID- 29659112
TI  - Characterization of Carboxylic Acid Reductases for Biocatalytic Synthesis of
      Industrial Chemicals.
AB  - Carboxylic acid reductases (CARs) catalyze the reduction of a broad range of
      carboxylic acids into aldehydes, which can serve as common biosynthetic
      precursors to many industrial chemicals. This work presents the systematic
      biochemical characterization of five carboxylic acid reductases from different
      microorganisms, including two known and three new ones, by using a panel of short
      chain dicarboxylic acids and hydroxy acids, which are common cellular
      metabolites. All enzymes displayed broad substrate specificities. Higher
      catalytic efficiencies were observed when the carbon chain length, either of the
      dicarboxylates or of the terminal hydroxy acids, was increased from C2 to C6 . In
      addition, when substrates of the same carbon chain length are compared,
      carboxylic acid reductases favor hydroxy acids over dicarboxylates as their
      substrates. Whole-cell bioconversions of eleven carboxylic acid substrates into
      the corresponding alcohols were investigated by coupling the CAR activity with
      that of an aldehyde reductase in Escherichia coli hosts. Alcohol products were
      obtained in yields ranging from 0.5 % to 71 %. The de novo stereospecific
      biosynthesis of propane-1,2-diol enantiomer was successfully demonstrated with
      use of CARs as the key pathway enzymes. E. coli strains accumulated 7.0 mm (R)
      1,2-PDO (1.0 % yield) or 9.6 mm (S)-1,2-PDO (1.4 % yield) from glucose. This
      study consolidates carboxylic acid reductases as promising enzymes for
      sustainable synthesis of industrial chemicals.

PMID- 29659113
TI  - Landscape evolution and nutrient rejuvenation reflected in Amazon forest canopy
      chemistry.
AB  - Terra firme forests make up more than three quarters of the western Amazon basin
      and are often considered functionally homogeneous in regional scale mapping and
      modelling efforts. However, the landforms underlying these systems are subject to
      dynamic processes of landscape evolution occurring within an otherwise
      geomorphically stable terrace formation. These processes may introduce systematic
      variability in local nutrient status of terra firme ecosystems. We utilised high
      resolution airborne topographic and imaging spectroscopy data, with directed
      field soil surveys, to reveal that active stream incision and patterns of soil
      rock derived nutrient availability drive foliar canopy chemistry distributions
      across seven catchments within a single terrace formation. These results strongly
      suggest that fine-scale geomorphic processes directly affect biogeochemical
      cycles throughout the lowland western Amazon. Furthermore, links between
      landscape evolution and foliar chemical distributions indicate that geomorphic
      processes drive the fine-scale spatial organisation of this tropical ecosystem,
      with implications for the functional assembly and biogeography of Amazonian
      forests.

PMID- 29659114
TI  - Cobalt-Catalyzed Intramolecular Reactions between a Vinylcyclopropane and an
      Alkyne: Switchable [5+2] Cycloaddition and Homo-Ene Pathways.
AB  - Cobalt-diphosphine catalysts have been found to promote intramolecular reactions
      between a vinylcyclopropane and an alkyne to selectively afford either the [5+2]
      cycloaddition product or the homo-ene reaction product under solvent control. The
      former product is exclusively formed in noncoordinating 1,2-dichloroethane,
      whereas the latter is dominant in coordinating solvents, such as acetonitrile and
      dimethylacetamide. Furthermore, a highly enantioselective variant of the homo-ene
      reaction afforded chiral tetrahydrofuran, pyrrolidine, and cyclopentane
      derivatives bearing 1,3-diene and alkylidene substituents.

PMID- 29659115
TI  - Topography shapes the structure, composition and function of tropical forest
      landscapes.
AB  - Topography is a key driver of tropical forest structure and composition, as it
      constrains local nutrient and hydraulic conditions within which trees grow. Yet,
      we do not fully understand how changes in forest physiognomy driven by topography
      impact other emergent properties of forests, such as their aboveground carbon
      density (ACD). Working in Borneo - at a site where 70-m-tall forests in alluvial
      valleys rapidly transition to stunted heath forests on nutrient-depleted dip
      slopes - we combined field data with airborne laser scanning and hyperspectral
      imaging to characterise how topography shapes the vertical structure, wood
      density, diversity and ACD of nearly 15 km2 of old-growth forest. We found that
      subtle differences in elevation - which control soil chemistry and hydrology -
      profoundly influenced the structure, composition and diversity of the canopy.
      Capturing these processes was critical to explaining landscape-scale
      heterogeneity in ACD, highlighting how emerging remote sensing technologies can
      provide new insights into long-standing ecological questions.

PMID- 29659116
TI  - Efficacy and safety of a new 5% minoxidil formulation in male androgenetic
      alopecia: A randomized, placebo-controlled, double-blind, noninferiority study.
AB  - BACKGROUND: Androgenetic alopecia (AGA) is the most common cause of hair loss in
      men. Topical minoxidil solutions can help to treat AGA but have to be applied
      continuously to be effective. OBJECTIVES: A new minoxidil formulation with
      improved cosmetic characteristics (DC0120, Pierre-Fabre Dermatologie) was tested
      for noninferiority vs a comparator minoxidil product (ALOSTIL(r) , Johnson &
      Johnson) in stimulating hair growth in men with AGA. METHODS: Two 10 cm2 areas on
      the scalp of each subject were randomized to receive DC0120, the comparator, or
      one of their corresponding vehicles, applied twice per day for 16 weeks.
      Nonvellus target area hair count (TAHC) was measured within treatment areas at
      baseline (day 1) and after 8 and 16 weeks by digital phototrichogram. RESULTS:
      Two hundred and twenty subjects were included and randomized, of which 210
      completed the study. The mean change in nonvellus TAHC between baseline and week
      16 was +22.0 hairs/cm2 (95% CI: 18.1; 25.9) in the DC0120 group and +20.5
      hairs/cm2 (95% CI: 16.6; 24.4) in the comparator group. The adjusted mean
      difference in TAHC changes between the two treatments was +1.5 hairs/cm2 (95% CI 
      2.3; 5.2), with the lower 95% confidence interval above the noninferiority
      threshold of -7 hairs/cm2 . This indicated that DC0120 was noninferior to the
      comparator. Both minoxidil treatments also increased nonvellus TAHC compared to
      vehicle groups at 8 and 16 weeks. No new safety signals were observed.
      CONCLUSIONS: DC0120 was as safe and effective as a similar marketed minoxidil
      product for stimulating hair growth in men with AGA.

PMID- 29659117
TI  - Evaluation of the relationship between peripheral pulse palpation and Doppler
      systolic blood pressure in dogs presenting to an emergency service.
AB  - OBJECTIVE: To assess the association between peripheral pulse palpation and
      Doppler-derived systolic blood pressure (SBP) measurement in dogs presenting to
      an emergency service. DESIGN: Prospective observational study. SETTING:
      University veterinary teaching hospital. ANIMALS: Ninety-three dogs that were
      presented to the emergency service. Dogs were eligible for inclusion in the study
      if a physical examination and a SBP measurement were performed prior to any
      interventions. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Both the
      femoral pulse quality and dorsal metatarsal pulse quality were digitally palpated
      and assessed as either strong, weak, or absent. The mean SBP in all dogs was 139
      mm Hg (+/- 39 mm Hg). Seventeen (17/93; 18%) dogs were hypotensive with a SBP <
      90 mm Hg (range, 40-88 mm Hg). The median SBP was not significantly different
      between dogs in the absent and present femoral pulse groups (P = 0.120) but the
      median SBP was significantly different between absent and present metatarsal
      pulse groups (P = 0.002). Dogs with absent metatarsal pulses were 7.6 times more
      likely to be hypotensive with a SBP < 90 mm Hg (OR, 7.6; 95% CI, 1.8-32) as
      compared to dogs with palpable metatarsal pulses. The sensitivity of absent
      metatarsal pulses to diagnose hypotension (SBP < 90 mm Hg) was 33% (95% CI, 10
      65%) and the specificity was 94% (95% CI, 86-98%). CONCLUSIONS: Absent metatarsal
      pulses are highly specific in the diagnosis of hypotension. However, dogs with
      palpable metatarsal pulses can still be hypotensive. Dorsal metatarsal pulse
      palpation is useful during triage assessment of dogs presenting to an emergency
      service, though it should not be used as the only indicator of a dog's
      cardiovascular stability and should not replace an actual blood pressure
      measurement.

PMID- 29659118
TI  - Risk of stroke associated with use of nonsteroidal anti-inflammatory drugs during
      acute respiratory infection episode.
AB  - BACKGROUND: Previous studies suggested that acute respiratory infection (ARI)
      could trigger stroke and that use of nonsteroidal anti-inflammatory drugs
      (NSAIDs) was associated with increased risk of stroke. In many countries, NSAIDs
      have been widely used among patients with ARI or common cold for pain and fever
      relief. However, studies evaluating whether NSAIDs use during ARI episodes may
      further increase the risk of stroke were very limited. METHODS AND RESULTS:
      During 2007 to 2011, 29 518 patients with an incident hospitalization of stroke
      were identified. The date of admission was defined as the index date. Using case
      crossover design, we compared the following exposure status between the case
      period (1- to 7-d period before the index date) and matched control period (366-
      to 372-d period before the index date): NSAIDs use during ARI episodes, ARI
      episodes without NSAIDs use, NSAIDs use only, or no exposure. Multivariable
      conditional regression models were used to estimate odds ratios adjusting
      potential confounders. The results suggested that NSAIDs use during ARI episodes
      was associated with a 2.3-fold increased risk of stroke (ischemic: adjusted odds
      ratio, aOR 2.27, 95% confidence interval, 95% CI, 2.00-2.58; hemorrhagic: aOR
      2.28, 95% CI, 1.71-3.02). We also determined that parenteral NSAIDs were
      associated with much higher risk of stroke in patients with ARI. CONCLUSIONS:
      Nonsteroidal anti-inflammatory drugs use during ARI episodes, especially
      parenteral NSAIDs use, was associated with a further increased risk of stroke.

PMID- 29659120
TI  - Patterns of depressive symptom remission during the treatment of seasonal
      affective disorder with cognitive-behavioral therapy or light therapy.
AB  - BACKGROUND: To elucidate mechanisms related to remission in winter seasonal
      affective disorder (SAD), we explored the course of individual depressive symptom
      offset across two distinct treatment modalities that show comparable outcomes at
      treatment endpoint: cognitive-behavioral therapy for SAD (CBT-SAD) and light
      therapy (LT). METHOD: One hundred seventy-seven adults with SAD in a depressive
      episode were randomized to 6-weeks of CBT-SAD (n = 88) or LT (n = 89). Symptoms
      were assessed via the 29-item Structured Interview Guide for the Hamilton Rating
      Scale for Depression-SAD Version (SIGH-SAD) at pretreatment and weekly during
      treatment. Survival analyses were conducted for the 17 SIGH-SAD items endorsed by
      more than 40 participants at pretreatment. Within each of the included symptoms,
      data from participants who endorsed the symptom at pretreatment and who had 3 or
      fewer weeks missing were included. RESULTS: For most (13/17; 76%) symptoms, CBT
      SAD and LT did not differ in time to remission. However, for four symptoms (early
      insomnia, psychic anxiety, hypersomnia, and social withdrawal), LT led to symptom
      remission more quickly than CBT-SAD. CONCLUSIONS: Symptom remission progressed
      comparably across CBT-SAD and LT for most symptoms. Despite the fact that the two
      treatments led to similar remission rates and improvements at treatment endpoint,
      for early insomnia, psychic anxiety, hypersomnia, and social withdrawal, LT led
      to symptom remission faster than CBT-SAD. These results suggest different
      mechanisms and pathways to the same therapeutic end. Speedier remission of early
      insomnia and hypersomnia is consistent with the theory that SAD is related to a
      pathological circadian phase-shift that can be corrected with LT.

PMID- 29659121
TI  - Glucagon-like peptide-1 ameliorates cardiac lipotoxicity in diabetic
      cardiomyopathy via the PPARalpha pathway.
AB  - Lipotoxicity cardiomyopathy is the result of excessive accumulation and oxidation
      of toxic lipids in the heart. It is a major threat to patients with diabetes.
      Glucagon-like peptide-1 (GLP-1) has aroused considerable interest as a novel
      therapeutic target for diabetes mellitus because it stimulates insulin secretion.
      Here, we investigated the effects and mechanisms of the GLP-1 analog exendin-4
      and the dipeptidyl peptidase-4 inhibitor saxagliptin on cardiac lipid metabolism
      in diabetic mice (DM). The increased myocardial lipid accumulation, oxidative
      stress, apoptosis, and cardiac remodeling and dysfunction induced in DM by low
      streptozotocin doses and high-fat diets were significantly reversed by exendin-4
      and saxagliptin treatments for 8 weeks. We found that exendin-4 inhibited
      abnormal activation of the (PPARalpha)-CD36 pathway by stimulating protein kinase
      A (PKA) but suppressing the Rho-associated protein kinase (ROCK) pathway in DM
      hearts, palmitic acid (PA)-treated rat h9c2 cardiomyocytes (CMs), and isolated
      adult mouse CMs. Cardioprotection in DM mediated by exendin-4 was abolished by
      combination therapy with the PPARalpha agonist wy-14643 but mimicked by PPARalpha
      gene deficiency. Therefore, the PPARalpha pathway accounted for the effects of
      exendin-4. This conclusion was confirmed in cardiac-restricted overexpression of
      PPARalpha mediated by adeno-associated virus serotype-9 containing a cardiac
      troponin T promoter. Our results provide the first direct evidence that GLP-1
      protects cardiac function by inhibiting the ROCK/PPARalpha pathway, thereby
      ameliorating lipotoxicity in diabetic cardiomyopathy.

PMID- 29659122
TI  - Short-term prey field lability constrains individual specialisation in resource
      selection and foraging site fidelity in a marine predator.
AB  - Spatio-temporally stable prey distributions coupled with individual foraging site
      fidelity are predicted to favour individual resource specialisation. Conversely,
      predators coping with dynamic prey distributions should diversify their
      individual diet and/or shift foraging areas to increase net intake. We studied
      individual specialisation in Scopoli's shearwaters (Calonectris diomedea) from
      the highly dynamic Western Mediterranean, using daily prey distributions together
      with resource selection, site fidelity and trophic-level analyses. As
      hypothesised, we found dietary diversification, low foraging site fidelity and
      almost no individual specialisation in resource selection. Crucially, shearwaters
      switched daily foraging tactics, selecting areas with contrasting prey of varying
      trophic levels. Overall, information use and plastic resource selection of
      individuals with reduced short-term foraging site fidelity allow predators to
      overcome prey field lability. Our study is an essential step towards a better
      understanding of individual responses to enhanced environmental stochasticity
      driven by global changes, and of pathways favouring population persistence.

PMID- 29659123
TI  - Advanced oxidation protein products induce pre-osteoblast apoptosis through a
      nicotinamide adenine dinucleotide phosphate oxidase-dependent, mitogen-activated
      protein kinases-mediated intrinsic apoptosis pathway.
AB  - Osteoblast apoptosis contributes to age-related bone loss. Advanced oxidation
      protein products (AOPPs) are recognized as the markers of oxidative stress and
      potent inducers of apoptosis. We have demonstrated that AOPP accumulation was
      correlated with age-related bone loss. However, the effect of AOPPs on the
      osteoblast apoptosis still remains unknown. Exposure of osteoblastic MC3T3-E1
      cells to AOPPs caused the excessive generation of reactive oxygen species (ROS)
      by activating nicotinamide adenine dinucleotide phosphate (NADPH) oxidases.
      Increased ROS induced phosphorylation of mitogen-activated protein kinases
      (MAPKs), which subsequently triggered intrinsic apoptosis pathway by inducing
      mitochondrial dysfunction, endoplasmic reticulum stress, and Ca2+ overload and
      eventually leads to apoptosis. Chronic AOPP loading in aged Sprague-Dawley rats
      induced osteoblast apoptosis and activated NADPH oxidase signaling cascade, in
      combination with accelerated bone loss and deteriorated bone microstructure. Our
      study suggests that AOPPs induce osteoblast apoptosis by the NADPH oxidase
      dependent, MAPK-mediated intrinsic apoptosis pathway.

PMID- 29659124
TI  - Evaluation of the effect of self-cutting and nonself-cutting thread designed
      implant with different thread depth on variable insertion torques: An
      histomorphometric analysis in rabbits.
AB  - PURPOSE: To evaluate of the effect of self-cutting and nonself-cutting thread
      designed implant with different thread depth on variable insertion torques. To
      evaluate the bone volume (BV) and bone to implant contact (BIC) in these
      variables MATERIALS AND METHODS: Mainly two thread design, V-shaped thread which
      is self-cutting and power thread design, which is nonself-cutting implants were
      considered for this study with a variation in thread depth of 0.4 and 0.6 mm for
      both the designs, respectively. A total of 32 CAD designed machined surface
      implant prototypes were manufactured of 4 mm in diameter and 8 mm in length were
      made, which were machined surfaced, which was placed in the femur of 16 New
      Zealand white rabbits. These were categorized under 2 groups; Group 1 and Group 2
      with insertion torques of <30 and >50 Ncm, respectively. After 4 weeks of
      healing, rabbits were sacrificed and histomophometric and histologic analyses
      were done to evaluate the bone response. RESULTS: Significantly, more BIC was
      recorded for high torque implants compared with low torque in power-shaped thread
      design (P value = .01*). BV for new bone formation was statistically significant
      for V-shaped thread design in high torque when compared with low torque (P value
      = .02*). CONCLUSION: The effect of the depth of the thread design was significant
      for the power-shaped design in enhancing BIC when compared with V-shaped thread
      design. With high torque V-shaped thread design had more new bone formation as
      compared with power-shaped thread design.

PMID- 29659125
TI  - Extremely preterm children exhibit increased interhemispheric connectivity for
      language: findings from fMRI-constrained MEG analysis.
AB  - Children born extremely preterm are at significant risk for cognitive impairment,
      including language deficits. The relationship between preterm birth and
      neurological changes that underlie cognitive deficits is poorly understood. We
      use a stories-listening task in fMRI and MEG to characterize language network
      representation and connectivity in children born extremely preterm (n = 15, <28
      weeks gestation, ages 4-6 years), and in a group of typically developing control
      participants (n = 15, term birth, 4-6 years). Participants completed a brief
      neuropsychological assessment. Conventional fMRI analyses revealed no significant
      differences in language network representation across groups (p > .05,
      corrected). The whole-group fMRI activation map was parcellated to define the
      language network as a set of discrete nodes, and the timecourse of neuronal
      activity at each position was estimated using linearly constrained minimum
      variance beamformer in MEG. Virtual timecourses were subjected to connectivity
      and network-based analyses. We observed significantly increased beta-band
      functional connectivity in extremely preterm compared to controls (p < .05).
      Specifically, we observed an increase in connectivity between left and right
      perisylvian cortex. Subsequent effective connectivity analyses revealed that
      hyperconnectivity in preterms was due to significantly increased information flux
      originating from the right hemisphere (p < 0.05). The total strength and density
      of the language network were not related to language or nonverbal performance,
      suggesting that the observed hyperconnectivity is a "pure" effect of prematurity.
      Although our extremely preterm children exhibited typical language network
      architecture, we observed significantly altered network dynamics, indicating
      reliance on an alternative neural strategy for the language task.

PMID- 29659126
TI  - Guanfacine decreases symptoms of cannabis withdrawal in daily cannabis smokers.
AB  - The alpha2a-adrenergic agonist, lofexidine, reduced cannabis withdrawal-related
      sleep disruption in the laboratory, but side effects (e.g. fatigue, hypotension)
      limit its utility as a treatment for cannabis use disorder. This study tested the
      potential efficacy and tolerability of a daily bedtime administration of the FDA
      approved alpha2a-adrenergic agonist, guanfacine, in a human laboratory model of
      cannabis use disorder. Daily, nontreatment-seeking cannabis smokers (13M, 2F)
      completed a within-subject study comprising two 9-day inpatient study phases.
      Each phase tested the effects of daily placebo or immediate-release guanfacine (2
      mg) on cannabis intoxication (5.6 percent THC; 2 days), withdrawal (4 days of
      abstinence) and subsequent 'relapse' (3 days of cannabis self-administration).
      Ratings of mood, sleep, cardiovascular effects, food intake, psychomotor
      performance and cannabis self-administration were assessed. An outpatient phase
      preceded each inpatient phase for medication clearance or dose induction. Under
      placebo medication conditions, cannabis abstinence produced significant
      withdrawal, including irritability, sleep disruption and anorexia. Guanfacine
      reduced ratings of irritability and improved objective measures of sleep during
      cannabis withdrawal relative to placebo but did not reduce cannabis self
      administration. Guanfacine was well tolerated with little evidence of fatigue and
      only small decreases in blood pressure: no dose was held due to hypotension.
      Thus, a single daily administration of guanfacine at bedtime improved sleep and
      mood during cannabis withdrawal relative to placebo. This positive signal
      supports further studies varying the guanfacine dose, formulation or frequency of
      administration, or combining it with other medications to increase the likelihood
      of having an impact on cannabis use.

PMID- 29659127
TI  - Launching Environmental Microbiology: 'The most effective way to do it, is to do
      it'.

PMID- 29659128
TI  - Activation of DNA demethylases attenuates aging-associated arterial stiffening
      and hypertension.
AB  - DNA methylation increases with age. The objective of this study was to
      investigate whether compound H, a potential activator of DNA demethylases,
      attenuates aging-related arterial stiffness and hypertension. Aged mice (24-27
      months) and adult mice (12 months) were used. Pulse wave velocity (PWV), a direct
      measure of arterial stiffness, and blood pressure (BP) were increased
      significantly in aged mice. Notably, daily treatments with compound H (15 mg/kg,
      IP) for 2 weeks significantly attenuated the aging-related increases in PWV and
      BP. Compound H abolished aging-associated downregulation of secreted Klotho (SKL)
      levels in both kidneys and serum likely by enhancing DNA demethylase activity and
      decreasing DNA methylation. Aging-related arterial stiffness was associated with
      accumulation of stiffer collagen and degradation of compliant elastin which are
      accompanied by increased expression of MMP2, MMP9, TGF-beta1, and TGF-beta3.
      These changes were effectively attenuated by compound H, suggesting rejuvenation
      of aged arteries. Compound H also rescued downregulation of Sirt1 deacetylase,
      AMPKalpha, and eNOS activities in aortas of aged mice. In cultured smooth muscle
      cells (SMCc) Klotho-deficient serum upregulated expression of MMPs and TGFbeta
      which, however, was not affected by compound H. In conclusion, compound H
      attenuates aging-associated arterial stiffness and hypertension by activation of
      DNA demethylase which increases renal SKL expression and consequently circulating
      SKL levels leading to activation of the Sirt1-AMPK-eNOS pathway in aortas of aged
      mice.

PMID- 29659129
TI  - Electrochemical Functional-Group-Tolerant Shono-type Oxidation of Cyclic
      Carbamates Enabled by Aminoxyl Mediators.
AB  - An electrochemical method has been developed for alpha-oxygenations of cyclic
      carbamates by using a bicyclic aminoxyl as a mediator and water as the
      nucleophile. The mediated electrochemical process enables substrate oxygenation
      to proceed at a potential that is approximately 1 V lower than the redox
      potential of the carbamate substrate. This feature allows for functional-group
      compatibility that is inaccessible with conventional Shono oxidations, which
      proceed by direct electrochemical substrate oxidation. This reaction also
      represents the first alpha-functionalization of non-activated cyclic carbamates
      with oxoammonium oxidants.

PMID- 29659130
TI  - MicroRNA-21 drives the switch to a synthetic phenotype in human saphenous vein
      smooth muscle cells.
AB  - Cardiovascular disease is a leading cause of morbidity and mortality. Smooth
      muscle cells (SMC) comprising the vascular wall can switch phenotypes from
      contractile to synthetic, which can promote the development of aberrant
      remodelling and intimal hyperplasia (IH). MicroRNA-21 (miR-21) is a short, non
      coding RNA that has been implicated in cardiovascular diseases including
      proliferative vascular disease and ischaemic heart disease. However, its
      involvement in the complex development of atherosclerosis has yet to be
      ascertained. Smooth muscle cells (SMC) were isolated from human saphenous veins
      (SV). miR-21 was over-expressed and the impact of this on morphology,
      proliferation, gene and protein expression related to synthetic SMC phenotypes
      monitored. Over-expression of miR-21 increased the spread cell area and
      proliferative capacity of SV-SMC and expression of MMP-1, whilst reducing RECK
      protein, indicating a switch to the synthetic phenotype. Furthermore, platelet
      derived growth factor BB (PDGF-BB; a growth factor implicated in
      vasculoproliferative conditions) was able to induce miR-21 expression via the
      PI3K and ERK signalling pathways. This study has revealed a mechanism whereby
      PDGF-BB induces expression of miR-21 in SV-SMC, subsequently driving conversion
      to a synthetic SMC phenotype, propagating the development of IH. Thus, these
      signaling pathways may be attractive therapeutic targets to minimise progression
      of the disease. (c) 2018 IUBMB Life, 70(7):649-657, 2018.

PMID- 29659131
TI  - Quantitative susceptibility mapping across two clinical field strengths: Contrast
      to-noise ratio enhancement at 1.5T.
AB  - BACKGROUND: Quantitative susceptibility mapping (QSM) is an MRI postprocessing
      technique that allows quantification of the spatial distribution of tissue
      magnetic susceptibility in vivo. Contributing sources include iron, blood
      products, calcium, myelin, and lipid content. PURPOSE: To evaluate the
      reproducibility and consistency of QSM across clinical field strengths of 1.5T
      and 3T and to optimize the contrast-to-noise ratio (CNR) at 1.5T through
      bandwidth tuning. STUDY TYPE: Prospective. SUBJECTS: Sixteen healthy volunteers
      (10 men, 6 women; age range 24-37; mean age 27.8 +/- 3.2 years). FIELD
      STRENGTHS/SEQUENCES: 1.5T and 3T systems from the same vendor. Four spoiled
      gradient echo (SPGR) sequences were designed with different acquisition
      bandwidths. ASSESSMENT: QSM reconstruction was achieved through a nonlinear
      morphology-enabled dipole inversion (MEDI) algorithm employing L1 regularization.
      CNR was calculated in seven regions of interest (ROIs), while reproducibility and
      consistency of QSM measurements were evaluated through voxel-based and region
      specific linear correlation analyses and Bland-Altman plots. STATISTICAL TESTS:
      Interclass correlation, Wilcoxon rank sum test, linear regression analysis, Bland
      Altman analysis, Welch's t-test. RESULTS: CNR analysis showed a statistically
      significant (P < 0.05) increase in four out of seven ROIs for the lowest
      bandwidth employed with respect to the highest (25.18% increase in CNR of caudate
      nucleus). All sequences reported an excellent correlation across field strength
      and bandwidth variation (R >= 0.96, widest limits of agreement from -18.7 to 25.8
      ppb) in the ROI-based analysis, while the correlation was found to be good for
      the voxel-based analysis of averaged maps (R >= 0.90, widest limits of agreement
      from -9.3 to 9.1 ppb). DATA CONCLUSION: CNR of QSM images reconstructed from 1.5T
      acquisitions can be enhanced through bandwidth tuning. MEDI-based QSM
      reconstruction demonstrated to be reproducible and consistent both across field
      strengths (1.5T and 3T) and bandwidth variation. LEVEL OF EVIDENCE: 1 Technical
      Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:1410-1420.

PMID- 29659133
TI  - An unusual case of coronary artery compression that did not preclude successful
      transcatheter pulmonary valve placement.
AB  - During transcatheter pulmonary valve placement, coronary compression observed
      during simultaneous right ventricular outflow tract angioplasty and coronary
      angiography typically contraindicates valve implantation. We present a unique
      patient with tetralogy of Fallot who underwent successful transcatheter Melody
      valve placement despite coronary compression observed during right ventricular
      outflow tract balloon angioplasty.

PMID- 29659132
TI  - Three dimensional extrusion printing induces polymer molecule alignment and cell
      organization within engineered cartilage.
AB  - Proper cell-material interactions are critical to remain cell function and thus
      successful tissue regeneration. Many fabrication processes have been developed to
      create microenvironments to control cell attachment and organization on a three
      dimensional (3D) scaffold. However, these approaches often involve heavy
      engineering and only the surface layer can be patterned. We found that 3D
      extrusion based printing at high temperature and pressure will result an aligned
      effect on the polymer molecules, and this molecular arrangement will further
      induce the cell alignment and different differentiation capacities. In
      particular, articular cartilage tissue is known to have zonal collagen fiber and
      cell orientation to support different functions, where collagen fibers and
      chondrocytes align parallel, randomly, and perpendicular, respectively, to the
      surface of the joint. Therefore, cell alignment was evaluated in a cartilage
      model in this study. We used small angle X-ray scattering analysis to
      substantiate the polymer molecule alignment phenomenon. The cellular response was
      evaluated both in vitro and in vivo. Seeded mesenchymal stem cells (MSCs) showed
      different morphology and orientation on scaffolds, as a combined result of
      polymer molecule alignment and printed scaffold patterns. Gene expression results
      showed improved superficial zonal chondrogenic marker expression in parallel
      aligned group. The cell alignment was successfully maintained in the animal model
      after 7 days with distinct MSC morphology between the casted and parallel printed
      scaffolds. This 3D printing induced polymer and cell alignment will have a
      significant impact on developing scaffold with controlled cell-material
      interactions for complex tissue engineering while avoiding complicated surface
      treatment, and therefore provides new concept for effective tissue repairing in
      future clinical applications. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res
      Part A: 106A: 2190-2199, 2018.

PMID- 29659134
TI  - Corrigendum.

PMID- 29659135
TI  - Response to the query raised by Lydia Bernardo.

PMID- 29659136
TI  - Response to Aggarwal and Das, Thiodigalactoside shows antitumour activity by beta
      galactoside-binding protein and regulatory T cells inhibition in oral squamous
      cell carcinoma.

PMID- 29659137
TI  - Treatment of acrodermatitis continua of Hallopeau with ustekinumab as monotherapy
      after failure of anti-TNF agents.

PMID- 29659139
TI  - Hydroxyapatite with Permanent Electrical Polarization: Preparation,
      Characterization, and Response against Inorganic Adsorbates.
AB  - Permanently polarized hydroxyapatite (HAp) particles have been prepared by
      applying a constant DC of 500 V at 1000  degrees C for 1 h to the sintered
      mineral. This process causes important chemical changes, as the formation of OH-
      defects (vacancies), the disappearance of hydrogenophosphate ions at the mineral
      surface layer, and structural variations reflected by the increment of the
      crystallinity. As a consequence, the electrochemical properties and electrical
      conductivity of the polarized mineral increase noticeably compared with as
      prepared and sintered samples. Moreover, these increments remain practically
      unaltered after several months. In addition, permanent polarization favours
      significantly the ability of HAp to adsorb inorganic bioadsorbates in comparison
      with as-prepared and sintered samples. The adsorbates cause a significant
      increment of the electrochemical stability and electrical conductivity with
      respect to bare polarized HAp, which may have many implications for biomedical
      applications of permanently polarized HAp.

PMID- 29659138
TI  - Quantification of airway fibrosis in asthma by flow cytometry.
AB  - Airway fibrosis is a prominent feature of asthma, contributing to the detrimental
      consequences of the disease. Fibrosis in the airway is the result of collagen
      deposition in the reticular lamina layer of the subepithelial tissue.
      Myofibroblasts are the leading cell type involved with this collagen deposition.
      Established methods of collagen deposition quantification present various issues,
      most importantly their inability to quantify current collagen biosynthesis
      occurring in airway myofibroblasts. Here, a novel method to quantify
      myofibroblast collagen expression in asthmatic lungs is described. Single cell
      suspensions of lungs harvested from C57BL/6 mice in a standard house dust mite
      model of asthma were employed to establish a flow cytometric method and compare
      collagen production in asthmatic and non-asthmatic lungs. Cells found to be CD45-
      alphaSMA+ , indicative of myofibroblasts, were gated, and median fluorescence
      intensity of the anti-collagen-I antibody labeling the cells was calculated. Lung
      myofibroblasts with no, medium, or high levels of collagen-I expression were
      distinguished. In asthmatic animals, collagen-I levels were increased in both
      medium and high expressers, and the number of myofibroblasts with high collagen-I
      content was elevated. Our findings determined that quantification of collagen-I
      deposition in myofibroblastic lung cells by flow cytometry is feasible in mouse
      models of asthma and indicative of increased collagen-I expression by asthmatic
      myofibroblasts. (c) 2018 International Society for Advancement of Cytometry.

PMID- 29659140
TI  - Enantioselective Formation of 2-Azetidinones by Ring-Assisted Cyclization of
      Interlocked N-(alpha-Methyl)benzyl Fumaramides.
AB  - The synthesis of optically active interlocked and non-interlocked 2-azetidinones
      by intramolecular cyclization of N-(alpha-methyl)benzyl fumaramide [2]rotaxanes
      is described. Two different strategies of asymmetric induction were tested in
      which the chiral group was located either proximal or distal to the reacting
      center of the thread. During these experiments, an interesting equilibration
      process inside the macrocyclic void occurred, thus leading to the cyclization
      through the (alpha-methyl)benzyl carbon atom and giving rise to beta-lactams,
      with a quaternary carbon atom, in an enantio- and diastereocontrolled manner.
      This cyclization also proceeds in kinetically stable chiral pseudo[2]rotaxanes,
      thus allowing further dethreading to provide enantioenriched 3,4-disubstituted
      trans-2-azetidinones. The stereochemical outcomes of the cyclizations inside and
      outside the macrocycle demonstrated noticeable differences.

PMID- 29659141
TI  - Risk and protective factors underlying depression and suicidal ideation in Autism
      Spectrum Disorder.
AB  - BACKGROUND: People with Autism Spectrum Disorder (ASD) are at significantly
      increased risk of suicidal thoughts and behavior. Given that social difficulties
      in ASD often lead to social isolation, which can in turn increase the risk for
      depression, this study examined loneliness and social support as potential risk
      and protective factors associated with depression and suicidal ideation. METHOD:
      The sample comprised 185 people (92 females) with ASD aged 14 to 80 years who
      were participating in a national survey. RESULTS: Forty-nine percent of
      participants returned scores in the clinical range for depression and 36%
      reported recent suicidal ideation. Females, comprising almost 50% of the sample,
      returned higher depression scores than males, however no differences were
      identified between males and females in terms of suicidal ideation. Regression
      analyses revealed that loneliness, satisfaction with social support, and ASD
      traits predicted depression scores. Satisfaction with social support predicted
      suicidal ideation, however, it was no longer a significant predictor after the
      effects of depression were taken into account. Path analysis showed that ASD
      trait severity was independently related to depression, that the effect of number
      of social supports on depression was mediated by loneliness and satisfaction with
      social support, and that effects of loneliness and satisfaction with social
      support on suicidal ideation were mediated by depression. The pattern of
      relationships was nearly identical for males and females. CONCLUSIONS: This study
      supports a model whereby loneliness and social support operate respectively as
      protective and risk factors for depression and suicidal ideation in ASD.

PMID- 29659142
TI  - An uneasy alliance: a nesting association between aggressive ants and equally
      fierce social wasps.
AB  - Although the Neotropical territorially dominant arboreal ant Azteca chartifex
      Forel is very aggressive towards any intruder, its populous colonies tolerate the
      close presence of the fierce polistine wasp Polybia rejecta (F.). In French
      Guiana, 83.33% of the 48 P. rejecta nests recorded were found side by side with
      those of A. chartifex. This nesting association results in mutual protection from
      predators (i.e., the wasps protected from army ants; the ants protected from
      birds). We conducted field studies, laboratory-based behavioral experiments and
      chemical analyses to elucidate the mechanisms allowing the persistence of this
      association. Due to differences in the cuticular profiles of the two species, we
      eliminated the possibility of chemical mimicry. Also, analyses of the carton
      nests did not reveal traces of marking on the envelopes. Because ant forager
      flows were not perturbed by extracts from the wasps' Dufour's and venom glands,
      we rejected any hypothetical action of repulsive chemicals. Nevertheless, we
      noted that the wasps "scraped" the surface of the upper part of their nest
      envelope using their mandibles, likely removing the ants' scent trails, and an
      experiment showed that ant foragers were perturbed by the removal of their scent
      trails. This leads us to use the term "erasure hypothesis." Thus, this nesting
      association persists thanks to a relative tolerance by the ants towards wasp
      presence and the behavior of the wasps that allows them to "contain" their
      associated ants through the elimination of their scent trails, direct attacks,
      "wing-buzzing" behavior and ejecting the ants.

PMID- 29659143
TI  - RASopathies are associated with a distinct personality profile.
AB  - Personality is a complex, yet partially heritable, trait. Although some Mendelian
      diseases like Williams-Beuren syndrome are associated with a particular
      personality profile, studies have failed to assign the personality features to a
      single gene or pathway. As a family of monogenic disorders caused by mutations in
      the Ras/MAPK pathway known to influence social behavior, RASopathies are likely
      to provide insight into the genetic basis of personality. Eighty subjects
      diagnosed with cardiofaciocutaneous syndrome, Costello syndrome,
      neurofibromatosis type 1, and Noonan syndrome were assessed using a parent-report
      BFQ-C (Big Five Questionnaire for Children) evaluating agreeableness,
      extraversion, conscientiousness, intellect/openness, and neuroticism, along with
      55 unaffected sibling controls. A short questionnaire was added to assess sense
      of humor. RASopathy subjects and sibling controls were compared for individual
      components of personality, multidimensional personality profiles, and individual
      questions using Student tests, analysis of variance, and principal component
      analysis. RASopathy subjects were given lower scores on average compared to
      sibling controls in agreeableness, extraversion, conscientiousness, openness, and
      sense of humor, and similar scores in neuroticism. When comparing the
      multidimensional personality profile between groups, RASopathies showed a
      distinct profile from unaffected siblings, but no difference in this global
      profile was found within RASopathies, revealing a common profile for the Ras/MAPK
      related disorders. In addition, several syndrome-specific strengths or weaknesses
      were observed in individual domains. We describe for the first time an
      association between a single pathway and a specific personality profile,
      providing a better understanding of the genetics underlying personality, and new
      tools for tailoring educational and behavioral approaches for individuals with
      RASopathies.

PMID- 29659144
TI  - The more-individuals hypothesis revisited: the role of community abundance in
      species richness regulation and the productivity-diversity relationship.
AB  - Species richness increases with energy availability, yet there is little
      consensus as to the exact processes driving this species-energy relationship. The
      most straightforward explanation is the more-individuals hypothesis (MIH). It
      states that higher energy availability promotes a higher total number of
      individuals in a community, which consequently increases species richness by
      allowing for a greater number of species with viable populations. Empirical
      support for the MIH is mixed, partially due to the lack of proper formalisation
      of the MIH and consequent confusion as to its exact predictions. Here, we review
      the evidence of the MIH and evaluate the reliability of various predictions that
      have been tested. There is only limited evidence that spatial variation in
      species richness is driven by variation in the total number of individuals. There
      are also problems with measures of energy availability, with scale-dependence,
      and with the direction of causality, as the total number of individuals may
      sometimes itself be driven by the number of species. However, even in such a case
      the total number of individuals may be involved in diversity regulation. We
      propose a formal theory that encompasses these processes, clarifying how the
      different factors affecting diversity dynamics can be disentangled.

PMID- 29659145
TI  - Ocular trauma in the Finnish elderly - Helsinki Ocular Trauma Study.
AB  - PURPOSE: To describe epidemiology, causes, treatments and outcomes of all ocular
      injuries in southern Finland among people aged 61 and older. METHODS: All new
      ocular trauma patients, admitted to the Helsinki University Eye Hospital, during
      1 year in 2011-2012. The data were from hospital records and prospectively from
      patient questionnaires. The follow-up time was 3 months. RESULTS: The incidence
      for ocular injuries among the elderly was 38/100 000/year. From 118 patients 69%
      were men. The mean age was 70.9 years old (median 67). The hospitalization rate
      was 14%. Injury types were minor traumas (48%), contusions (22%), chemical
      injuries (10%), eyelid wounds (8%), open globe injuries (OGI; 7%) and orbital
      fractures (5%). The injuries occurred at home (58%), institutions (12%) and in
      other public places (12%). The main causes of ocular injury were falls (22%),
      sticks (19%), superficial foreign bodies (18%) and chemicals (12%). All OGI and
      88% of contusions needed a lifelong follow-up. A permanent visual or functional
      impairment occurred in 15 (13%) patients. Of these 53% were OGI, 40% contusions
      and 7% chemical injuries. The causes of permanent injuries were falls (seven
      cases, 47%), work tools, sports equipment, sticks, chemicals and eyeglasses. The
      incidence for legal blindness was 2.3/100 000. CONCLUSION: Minor trauma was the
      most frequent type, and home was the location of the most occurred eye injuries.
      Falls were the most frequent and serious cause, but behavioural causes were not
      significant. Preventive measures should be directed towards the main identified
      causes and risk factors of the eye injuries in the elderly.

PMID- 29659146
TI  - Curcumin accelerates cutaneous wound healing via multiple biological actions: The
      involvement of TNF-alpha, MMP-9, alpha-SMA, and collagen.
AB  - Curcumin, a constituent of the turmeric plant, has antitumor, anti-inflammatory,
      and antioxidative effects, but its effects on wound healing are unclear. We
      created back wounds in 72 mice and treated them with or without topical curcumin
      (0.2 mg/mL) in Pluronic F127 gel (20%) daily for 3, 5, 7, 9, and 12 days. Healing
      in wounds was evaluated from gross appearance, microscopically by haematoxylin
      and eosin staining, by immunohistochemistry for tumour necrosis factor alpha and
      alpha smooth muscle actin, and by polymerase chain reaction amplification of mRNA
      expression levels. Treatment caused fast wound closure with well-formed
      granulation tissue dominated by collagen deposition and regenerating epithelium.
      Curcumin increased the levels of tumour necrosis factor alpha mRNA and protein in
      the early phase of healing, which then decreased significantly. However, these
      levels remained high in controls. Levels of collagen were significantly higher in
      curcumin-treated wounds. Immunohistochemical staining for alpha smooth muscle
      actin was increased in curcumin-treated mice on days 7 and 12. Curcumin treatment
      significantly suppressed matrix metallopeptidase-9 and stimulated alpha smooth
      muscle levels in tumour necrosis factor alpha-treated fibroblasts via nuclear
      factor kappa B signalling. Thus, topical curcumin accelerated wound healing in
      mice by regulating the levels of various cytokines.

PMID- 29659147
TI  - Cross-Plane Carrier Transport in Van der Waals Layered Materials.
AB  - The mechanisms of carrier transport in the cross-plane crystal orientation of
      transition metal dichalcogenides are examined. The study of in-plane electronic
      properties of these van der Waals compounds has been the main research focus in
      recent years. However, the distinctive physical anisotropies, short-channel
      physics, and tunability of cross layer interactions can make the study of their
      electronic properties along the out-of-plane crystal orientation valuable. Here,
      the out-of-plane carrier transport mechanisms in niobium diselenide and hafnium
      disulfide are explored as two broadly different representative materials.
      Temperature-dependent current-voltage measurements are preformed to examine the
      mechanisms involved. First principles simulations and a tunneling model are used
      to understand these results and quantify the barrier height and hopping distance
      properties. Using Raman spectroscopy, the thermal response of the chemical bonds
      is directly explored and the insight into the van der Waals gap properties is
      acquired. These results indicate that the distinct cross-plane carrier transport
      characteristics of the two materials are a result of material thermal properties
      and thermally mediated transport of carriers through the van der Waals gaps.
      Exploring the cross-plane electron transport, the exciting physics involved is
      unraveled and potential new avenues for the electronic applications of van der
      Waals layers are inspired.

PMID- 29659148
TI  - Hydrogen sulphide increases pulmonary veins and atrial arrhythmogenesis with
      activation of protein kinase C.
AB  - Hydrogen sulphide (H2 S), one of the most common toxic air pollutants, is an
      important aetiology of atrial fibrillation (AF). Pulmonary veins (PVs) and left
      atrium (LA) are the most important AF trigger and substrate. We investigated
      whether H2 S may modulate the arrhythmogenesis of PVs and atria. Conventional
      microelectrodes and whole-cell patch clamp were performed in rabbit PV,
      sinoatrial node (SAN) or atrial cardiomyocytes before and after the perfusion of
      NaHS with or without chelerythrine (a selective PKC inhibitor), rottlerin (a
      specific PKC delta inhibitor) or KB-R7943 (a NCX inhibitor). NaHS reduced
      spontaneous beating rates, but increased the occurrences of delayed
      afterdepolarizations and burst firing in PVs and SANs. NaHS (100 MUmol/L)
      increased IKATP and INCX in PV and LA cardiomyocytes, which were attenuated by
      chelerythrine (3 MUmol/L). Chelerythrine, rottlerin (10 MUmol/L) or KB-R7943 (10
      MUmol/L) attenuated the arrhythmogenic effects of NaHS on PVs or SANs. NaHS
      shortened the action potential duration in LA, but not in right atrium or in the
      presence of chelerythrine. NaHS increased PKC activity, but did not translocate
      PKC isoforms alpha, epsilon to membrane in LA. In conclusion, through protein
      kinase C signalling, H2 S increases PV and atrial arrhythmogenesis, which may
      contribute to air pollution-induced AF.

PMID- 29659150
TI  - Chronic obstructive pulmonary disease in patients with chronic thromboembolic
      pulmonary hypertension: Prevalence and implications for surgical treatment
      outcome.
AB  - OBJECTIVE: The aim of our study was to investigate the prevalence of chronic
      obstructive pulmonary disease (COPD) in patients with chronic thromboembolic
      pulmonary hypertension (CTEPH) and examine their impact on the results of
      pulmonary thrombendarterectomy (PEA). METHODS: We enrolled 136 patients with
      CTEPH who scheduled for elective PEA. Pulmonary function tests (PFTs) including
      full-body plethysmography with bronchodilation test and lung diffusion capacity
      assessment were performed in all patients prior to surgery treatment. The
      diagnosis of COPD was verified in accordance with the recommendations of the
      Global Initiative for Chronic Obstructive Lung Disease 2017. The effect of COPD
      on perioperative characteristics, complications, in-hospital and one-year
      mortality of patients with CTEPH were analysed. RESULTS: In the study group with
      CTEPH the prevalence of COPD was 23%. In 13% of patients, COPD was first
      detected. The results of PFTs showed more severe airflow limitations with
      obstructive pattern in patients with concomitant COPD, as well as a more
      pronounced decrease in the lung diffusion capacity. The presence of COPD in
      patients with CTEPH significantly increases the risk of residual pulmonary
      hypertension in the early postoperative period of PEA (OR = 6.2 (1.90-10.27), P =
      .002), duration of hospital stay (OR = 1.1 (1.01-1.20), P = .020) and the risk of
      in-hospital mortality (OR = 4.4 (1.21-16.19), P = .023). The lung diffusion
      capacity revealed significant negative associations with the duration of hospital
      stay and in-hospital mortality (OR 0.87 (0.74-0.98), P = .012). CONCLUSION: COPD
      in patients with CTEPH significantly increases the risk of residual pulmonary
      hypertension, in-hospital mortality and increases the duration of hospital stay
      after PEA.

PMID- 29659149
TI  - Exploring the effect of previous inactivated influenza vaccination on seasonal
      influenza vaccine effectiveness against medically attended influenza: Results of
      the European I-MOVE multicentre test-negative case-control study, 2011/2012
      2016/2017.
AB  - BACKGROUND: Results of previous influenza vaccination effects on current season
      influenza vaccine effectiveness (VE) are inconsistent. OBJECTIVES: To explore
      previous influenza vaccination effects on current season VE among population
      targeted for vaccination. METHODS: We used 2011/2012 to 2016/2017 I-MOVE primary
      care multicentre test-negative data. For each season, we compared current season
      adjusted VE (aVE) between individuals vaccinated and unvaccinated in previous
      season. Using unvaccinated in both seasons as a reference, we then compared aVE
      between vaccinated in both seasons, current only, and previous only. RESULTS: We
      included 941, 2645 and 959 influenza-like illness patients positive for influenza
      A(H1N1)pdm09, A(H3N2) and B, respectively, and 5532 controls. In 2011/2012,
      2014/2015 and 2016/2017, A(H3N2) aVE point estimates among those vaccinated in
      previous season were -68%, -21% and -19%, respectively; among unvaccinated in
      previous season, these were 33%, 48% and 46%, respectively (aVE not computable
      for influenza A(H1N1)pdm09 and B). Compared to current season vaccination only,
      VE for both seasons' vaccination was (i) similar in two of four seasons for
      A(H3N2) (absolute difference [ad] 6% and 8%); (ii) lower in three of four seasons
      for influenza A(H1N1)pdm09 (ad 18%, 26% and 29%), in two seasons for influenza
      A(H3N2) (ad 27% and 39%) and in two of three seasons for influenza B (ad 26% and
      37%); (iii) higher in one season for influenza A(H1N1)pdm09 (ad 20%) and
      influenza B (ad 24%). CONCLUSIONS: We did not identify any pattern of previous
      influenza vaccination effect. Prospective cohort studies documenting influenza
      infections, vaccinations and vaccine types are needed to understand previous
      influenza vaccinations' effects.

PMID- 29659151
TI  - Story-Making as Methodology: Disrupting Dominant Stories through Multimedia
      Storytelling.
AB  - In this essay, we discuss multimedia story-making methodologies developed through
      Re*Vision: The Centre for Art and Social Justice that investigates the power of
      the arts, especially story, to positively influence decision makers in diverse
      sectors. Our story-making methodology brings together majority and minoritized
      creators to represent previously unattended experiences (e.g., around mind-body
      differences, queer sexuality, urban Indigenous identity, and Inuit cultural
      voice) with an aim to building understanding and shifting policies/practices that
      create barriers to social inclusion and justice. We analyze our ongoing efforts
      to rework our storytelling methodology, spotlighting acts of revising carried out
      by facilitators and researchers as they/we redefine methodological terms for each
      storytelling context, by researcher-storytellers as they/we rework material from
      our lives, and by receivers of the stories as we revise our assumptions about
      particular embodied histories and how they are defined within dominant cultural
      narratives and institutional structures. This methodology, we argue, contributes
      to the existing qualitative lexicon by providing innovative new approaches not
      only for chronicling marginalized/misrepresented experiences and critically
      researching selves, but also for scaffolding intersectional alliances and for
      imagining more just futures.

PMID- 29659152
TI  - Cranial Pair I: The Olfactory Nerve.
AB  - The olfactory nerve constitutes the first cranial pair. Compared with other
      cranial nerves, it depicts some atypical features. First, the olfactory nerve
      does not form a unique bundle. The olfactory axons join other axons and form
      several small bundles or fascicles: the fila olfactoria. These fascicles leave
      the nasal cavity, pass through the lamina cribrosa of the ethmoid bone and enter
      the brain. The whole of these fascicles is what is known as the olfactory nerve.
      Second, the olfactory sensory neurons, whose axons integrate the olfactory nerve,
      connect the nasal cavity and the brain without any relay. Third, the olfactory
      nerve is composed by unmyelinated axons. Fourth, the olfactory nerve contains
      neither Schwann cells nor oligodendrocytes wrapping its axons. But it contains
      olfactory ensheathing glia, which is a type of glia unique to this nerve. Fifth,
      the olfactory axons participate in the circuitry of certain spherical structures
      of neuropil that are unique in the brain: the olfactory glomeruli. Sixth, the
      axons of the olfactory nerve are continuously replaced and their connections in
      the central nervous system are remodeled continuously. Therefore, the olfactory
      nerve is subject to lifelong plasticity. Finally seventh, the olfactory nerve can
      be a gateway for the direct entrance of viruses, neurotoxins and other
      xenobiotics to the brain. In the same way, it can be used as a portal of entry to
      the brain for therapeutic substances, bypassing the blood-brain barrier. In this
      article, we analyze some features of the anatomy and physiology of the first
      cranial pair. Anat Rec, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29659153
TI  - Neural crest and the patterning of vertebrate craniofacial muscles.
AB  - Patterning of craniofacial muscles overtly begins with the activation of lineage
      specific markers at precise, evolutionarily conserved locations within
      prechordal, lateral, and both unsegmented and somitic paraxial mesoderm
      populations. Although these initial programming events occur without influence of
      neural crest cells, the subsequent movements and differentiation stages of most
      head muscles are neural crest-dependent. Incorporating both descriptive and
      experimental studies, this review examines each stage of myogenesis up through
      the formation of attachments to their skeletal partners. We present the
      similarities among developing muscle groups, including comparisons with trunk
      myogenesis, but emphasize the morphogenetic processes that are unique to each
      group and sometimes subsets of muscles within a group. These groups include
      branchial (pharyngeal) arches, which encompass both those with clear homologues
      in all vertebrate classes and those unique to one, for example, mammalian facial
      muscles, and also extraocular, laryngeal, tongue, and neck muscles. The presence
      of several distinct processes underlying neural crest:myoblast/myocyte
      interactions and behaviors is not surprising, given the wide range of both
      quantitative and qualitative variations in craniofacial muscle organization
      achieved during vertebrate evolution.

PMID- 29659154
TI  - Comparison of local versus general anesthesia in patients undergoing
      transcatheter aortic valve replacement: An updated meta-analysis.

PMID- 29659155
TI  - Breaking with tradition: A scoping meta-analysis analyzing the effects of student
      centered learning and computer-aided instruction on student performance in
      anatomy.
AB  - While prior meta-analyses in anatomy education have explored the effects of
      laboratory pedagogies and histology media on learner performance, the effects of
      student-centered learning (SCL) and computer-aided instruction (CAI) have not
      been broadly evaluated. This research sought to answer the question, "How
      effective are student-centered pedagogies and CAI at increasing student knowledge
      gains in anatomy compared to traditional didactic approaches?" Relevant studies
      published within the past 51 years were searched using five databases.
      Predetermined eligibility criteria were applied to the screening of titles and
      abstracts to discern their appropriateness for study inclusion. A summary effect
      size was estimated to determine the effects of SCL and CAI on anatomy performance
      outcomes. A moderator analysis of study features was also performed. Of the 3,035
      records screened, 327 underwent full-text review. Seven studies, which comprised
      1,564 participants, were included in the SCL analysis. An additional 19 studies
      analyzed the effects of CAI in the context of 2,570 participants. Upon comparing
      SCL to traditional instruction, a small positive effect on learner performance
      was detected (standardized mean difference (SMD = 0.24; [CI = 0.07, 0.42]; P =
      0.006). Likewise, students with CAI exposure moderately outscored those with
      limited or no access to CAI (SMD = 0.59; [CI = 0.20, 0.98]; P = 0.003). Further
      analysis of CAI studies identified effects (P <= 0.001) for learner population,
      publication period, interventional approach, and intervention frequency. Overall,
      learners exposed to SCL and supplemental CAI outperformed their more classically
      trained peers as evidenced by increases in short-term knowledge gains. Anat Sci
      Educ. (c) 2018 American Association of Anatomists.

PMID- 29659156
TI  - Mosaic patterns of B-vitamin synthesis and utilization in a natural marine
      microbial community.
AB  - Aquatic environments contain large communities of microorganisms whose
      synergistic interactions mediate the cycling of major and trace nutrients,
      including vitamins. B-vitamins are essential coenzymes that many organisms cannot
      synthesize. Thus, their exchange among de novo synthesizers and auxotrophs is
      expected to play an important role in the microbial consortia and explain some of
      the temporal and spatial changes observed in diversity. In this study, we
      analyzed metatranscriptomes of a natural marine microbial community, diel sampled
      quarterly over one year to try to identify the potential major B-vitamin
      synthesizers and consumers. Transcriptomic data showed that the best-represented
      taxa dominated the expression of synthesis genes for some B-vitamins but lacked
      transcripts for others. For instance, Rhodobacterales dominated the expression of
      vitamin-B12 synthesis, but not of vitamin-B7 , whose synthesis transcripts were
      mainly represented by Flavobacteria. In contrast, bacterial groups that
      constituted less than 4% of the community (e.g., Verrucomicrobia) accounted for
      most of the vitamin-B1 synthesis transcripts. Furthermore, ambient vitamin-B1
      concentrations were higher in samples collected during the day, and were
      positively correlated with chlorophyll-a concentrations. Our analysis supports
      the hypothesis that the mosaic of metabolic interdependencies through B-vitamin
      synthesis and exchange are key processes that contribute to shaping microbial
      communities in nature.

PMID- 29659157
TI  - Francis Fontan 1929-2018.

PMID- 29659158
TI  - Standard abbreviations.

PMID- 29659159
TI  - Spinal Accessory Motor Neurons in the Mouse: A Special Type of Branchial Motor
      Neuron?
AB  - The spinal accessory nerve arises from motor neurons in the upper cervical spinal
      cord. The axons of these motor neurons exit dorsal to the ligamentum denticulatum
      and form the spinal accessory nerve. The nerve ascends in the spinal subarachnoid
      space to enter the posterior cranial fossa through the foramen magnum. The spinal
      accessory nerve then turns caudally to exit through the jugular foramen alongside
      the vagus and glossopharyngeal nerves, and then travels to supply the
      sternomastoid and trapezius muscles in the neck. The unusual course of the spinal
      accessory nerve has long prompted speculation that it is not a typical spinal
      motor nerve and that it might represent a caudal remnant of the branchial motor
      system. Our cell lineage tracing data, combined with images from public
      databases, show that the spinal accessory motor neurons in the mouse transiently
      express Phox2b, a transcription factor that is required for development of brain
      stem branchial motor nuclei. While this is strong prima facie evidence that the
      spinal accessory motor neurons should be classified as branchial motor, the
      evolutionary history of these motor neurons in anamniote vertebrates suggests
      that they may be considered to be an atypical branchial group that possesses both
      branchial and somatic characteristics. Anat Rec, 2018. (c) 2018 Wiley
      Periodicals, Inc.

PMID- 29659160
TI  - The Accessory Nerve: A Comprehensive Review of Its Anatomy, Development,
      Variations, Landmarks and Clinical Considerations.
AB  - INTRODUCTION: The eleventh cranial nerve, the accessory nerve, has a complex and
      unique anatomy and has been the subject of much debate. Herein, we review the
      morphology, embryology, surgical anatomy, and clinical manifestations of the
      accessory nerve. Included in this review, we mention variant anatomy, molecular
      development, histology, and imaging of the accessory nerve. CONCLUSIONS: The
      accessory nerve continues to be a topic of much discussion regarding its exact
      function and in particular to its cranial roots. Recently, various surgical
      procedures have been devised that repurpose the accessory nerve (e.g.,
      lengthening procedures, contralateral neurotization procedures). Currently, we
      continue to learn and have much to learn about this lower cranial nerve. Anat
      Rec, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29659161
TI  - Neurovascular Relations of the Trigeminal Nerve in Asymptomatic Individuals
      Studied with High-Resolution Three-Dimensional Magnetic Resonance Imaging.
AB  - Neurovascular compression (NVC) is considered the main cause of classic
      trigeminal neuralgia (TN) and may be surgically addressed with microvascular
      decompression (MVD). Preoperative high-resolution three-dimensional magnetic
      resonance has proven a reliable tool to diagnose NVC in patients with refractory
      TN undergoing MVD. However, there is still scarce data regarding the rate,
      degree, and characteristics of neurovascular compression in asymptomatic
      individuals. This article describes the vascular relations of the trigeminal
      nerve in the cerebellopontine angle (CPA) in 100 subjects without known TN
      studied with 3.0T FIESTA (Fast Imaging Employing Steady-state Acquisition) MRI
      sequence. A NVC was observed in 142 (71%) of the 200 nerves with a 75% rate of
      bilateral NVC. Of the nerves with NVC, 92.3% showed a mere contact (Grade 1)
      without distortion and 78% occurred at the cisternal segment. This most common
      vessel causing the NVC was a vein (66%) followed by the superior cerebellar
      artery (28%). No significant reduction in diameter suggesting atrophy was seen in
      the nerves with NVC. The results indicate a high rate of mild, distal and
      predominantly venous vascular contact with the trigeminal nerve at the CPA in
      asymptomatic individuals. This clearly contrasts with the usual pattern of NVC
      observed in TN that is generally a severe, proximal, and arterial compression.
      Knowledge about the frequent NVC in asymptomatic individuals and its features is
      essential for interpreting preoperative MRI in patients with refractory classical
      TN considered for surgery. Anat Rec, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29659162
TI  - Clinical utility of complement-dependent C3d assay in kidney recipients
      presenting with late allograft dysfunction.
AB  - The objective of this study was to evaluate the utility of a complement-dependent
      C3d assay to risk stratify donor-specific antibodies (DSA) in a multicenter
      cohort of kidney recipients presenting with new-onset clinical dysfunction. A
      total of 106 subjects with evidence of DSA at a mean period of 5.3 +/- 5.0 years
      posttransplant underwent testing using C3d reagents. C3d positivity was strongly
      associated with both the peak and sum IgG DSA MFI, with 98.3% (n = 57/58) of
      strongly reactive sera (peak MFI > 10 000) eliciting a positive signal. Patients
      with C3d+ DSA had a higher creatinine (P = .03), more significant graft fibrosis
      (P = .035), and a faster rate of graft loss posttest compared to those with C3d-
      DSA (P = .05). Subanalysis of patients with low-moderate level DSA confirmed the
      inferior outcome associated with C3d positivity. Despite the prognostic value of
      C3d as a stand-alone test, the assay did not provide independent risk prediction
      after incorporation of graft fibrosis in a multivariate model (P = .94). Overall,
      C3d offered limited discriminatory value for strong DSA with peak IgG MFI > 10
      000 and in patients where histologic data is available, but its utilization may
      be considered in those with low-moderate level DSA and where an allograft biopsy
      is not accessible.

PMID- 29659163
TI  - Synthesis, Characterization, and Initial Biological Evaluation of [99m Tc]Tc
      Tricarbonyl-labeled DPA-alpha-MSH Peptide Derivatives for Potential Melanoma
      Imaging.
AB  - alpha-Melanocyte stimulating hormone (alpha-MSH) derivatives target the
      melanocortin-1 receptor (MC1R) specifically and selectively. In this study, the
      alpha-MSH-derived peptide NAP-NS1 (Nle-Asp-His-d-Phe-Arg-Trp-Gly-NH2 ) with and
      without linkers was conjugated with 5-(bis(pyridin-2-ylmethyl)amino)pentanoic
      acid (DPA-COOH) and labeled with [99m Tc]Tc-tricarbonyl by two methods. With the
      one-pot method the labeling was faster than with the two-pot method, while
      obtaining similarly high yields. Negligible trans-chelation and high stability in
      physiological solutions was determined for the [99m Tc]Tc-tricarbonyl-peptide
      conjugates. Coupling an ethylene glycol (EG)-based linker increased the
      hydrophilicity. The peptide derivatives displayed high binding affinity in murine
      B16F10 melanoma cells as well as in human MeWo and TXM13 melanoma cell
      homogenates. Preliminary in vivo studies with one of the [99m Tc]Tc-tricarbonyl
      peptide conjugates showed good stability in blood and both renal and
      hepatobiliary excretion. Biodistribution was performed on healthy rats to gain
      initial insight into the potential relevance of the 99m Tc-labeled peptides for
      in vivo imaging.

PMID- 29659164
TI  - Development and Functional Organization of the Cranial Nerves in Lampreys.
AB  - Lampreys, together with hagfishes, are the only extant representatives of the
      oldest branch of vertebrates, the agnathans, which are the sister group of
      gnathostomes; therefore, studies on these animals are of great evolutionary
      significance. Lampreys exhibit a particular life cycle with remarkable changes in
      their behavior, concomitant, in part, with important modifications in the head
      and its musculature, which might influence the development of the cranial nerves.
      In this context, some cranial nerves such as the optic nerve and the ocular motor
      nerves, which develop slowly during an extremely long larval period lasting more
      than five years, have been more thoroughly investigated; however, much less
      experimental information is available about others, such as the facial or the
      hypoglossal nerves. In addition, the possible existence of a "true" accessory
      nerve in these animals is still a matter of conjecture. Although growing in last
      decades, investigations on the physiology of the lamprey cranial nerves is
      scanty. This review focuses on past and recent findings that have contributed to
      characterize the anatomical organization of the cranial nerves in lampreys,
      including their components and nuclei, and their relations in the brain; in
      addition, comments on their development and functional role are also included.
      Anat Rec, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29659165
TI  - Improving academic performance of sport and exercise science undergraduate
      students in gross anatomy using a near-peer teaching program.
AB  - Peer and near-peer teaching programs are common in medical undergraduate courses.
      However, there are no studies that have investigated the effectiveness of a near
      peer teaching program on the academic performance of undergraduate students
      pursuing sport and exercise science coursework. This study was conducted to
      analyze the effectiveness of such a program for students who participated in a
      course on the functional anatomy of the locomotor apparatus. A total of 39
      student participants were divided into two groups: students in one group
      voluntarily attended at least one session of a near-peer teaching program, and
      students in the other group attended no sessions. The final grade (range 0-100%)
      was recorded and used as an indicator of academic performance. The final grade of
      students who attended the near-peer teaching program (69.5 +/- 16.0%) was 38.7%
      higher (P = 0.002, d = 1.06) than those who did not (50.1 +/- 20.4%). When the
      academic performance of the same students was evaluated in another course
      (exercise physiology) that did not offer a near-peer teaching program, there were
      no significant differences between the groups (students who attended or did not
      attend the near-peer teaching program). A significant positive association was
      found between near-peer teaching program frequency and the number of students
      approved and not approved in the course (P = 0.041). A significant difference (P
      = 0.001) was found in the attendance at regular classes between the group who
      participated in the near-peer teaching program (median: 62 hours; IQR
      [interquartile ranges]: 4.0 hours) and those who did not (median: 58 hours; IQR:
      4.0 hours). Gender was not a moderating factor on academic performance or near
      peer teaching program attendance. These results highlight the effectiveness of a
      near-peer teaching program on the academic performance of students from a sport
      and exercise science degree program while enrolled in an anatomy course. Anat Sci
      Educ. (c) 2018 American Association of Anatomists.

PMID- 29659166
TI  - Strategies to improve tumor penetration of nanomedicines through nanoparticle
      design.
AB  - Nanoparticles (NPs) have emerged as an effective means to deliver therapeutic
      drugs for cancer treatment, as they can preferentially accumulate at tumor site
      through the enhanced permeability and retention effect. Various forms of NPs
      including liposomes, polymeric micelles, and inorganic particles have been used
      for therapeutic applications. However, the therapeutic benefits of nanomedicines
      are suboptimal. Although many possible reasons may account for the compromised
      therapeutic efficacy, the inefficient tumor penetration can be a vital obstacle.
      Tumor develops characteristic pathological environment, such as abnormal
      vasculature, elevated interstitial fluid pressure, and dense extracellular
      matrix, which intrinsically hinder the transport of nanomedicines in the tumor
      parenchyma. The physicochemical properties of the NPs such as size, shape, and
      surface charge have profound effect on tumor penetration. In this review, we will
      highlight the factors that affect the transport of NPs in solid tumor, and then
      elaborate on designing strategies to improve NPs' penetration and uniform
      distribution inside the tumor interstitium. This article is categorized under:
      Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

PMID- 29659167
TI  - The bidirectional association among female hormone-related cancers: breast,
      ovary, and uterine corpus.
AB  - Breast, ovarian, and uterine corpus cancers are common female cancers and
      categorized as hormone-related diseases. Previous studies reported a
      unidirectional relationship for each cancer, but few studied the reciprocal
      association in the same cohort. A population-based study was carried out in
      Taiwan to test the hypothesis that there are pairwise bidirectional associations
      among these cancers. Using the same cohort of 110,112 cases with primary female
      cancers including uterine corpus cancer (11,146 cases), ovarian cancer (12,139
      cases), or breast cancer (86,827 cases) from the Taiwan Cancer Registry from 1979
      to 2008, the pairwise risks of second cancer among uterine corpus, ovary, and
      breast cancer cases were evaluated by standardized incidence ratios (SIRs) and
      the corresponding 95% confidence intervals (CIs) to quantify the excess of second
      malignancies. A reciprocal relationship was found for these three female cancers,
      particularly most prominent between uterine and ovarian cancers, followed by
      breast and uterine cancers as well as breast and ovarian cancers. The overall
      risk of second cancers was highest within the first 5 years after the diagnosis
      of primary cancer. The bidirectional relationships suggest common risk factors
      among these three female cancers. This is the largest cohort study to focus on
      the bidirectional associations among hormone-related cancers in Asian women, and
      these results could aid in the development of early prevention strategies and
      follow-up surveillance programs.

PMID- 29659168
TI  - Metformin alleviates human cellular aging by upregulating the endoplasmic
      reticulum glutathione peroxidase 7.
AB  - Metformin, an FDA-approved antidiabetic drug, has been shown to elongate lifespan
      in animal models. Nevertheless, the effects of metformin on human cells remain
      unclear. Here, we show that low-dose metformin treatment extends the lifespan of
      human diploid fibroblasts and mesenchymal stem cells. We report that a low dose
      of metformin upregulates the endoplasmic reticulum-localized glutathione
      peroxidase 7 (GPx7). GP*7 expression levels are decreased in senescent human
      cells, and GPx7 depletion results in premature cellular senescence. We also
      indicate that metformin increases the nuclear accumulation of nuclear factor
      erythroid 2-related factor 2 (Nrf2), which binds to the antioxidant response
      elements in the GPX7 gene promoter to induce its expression. Moreover, the
      metformin-Nrf2-GPx7 pathway delays aging in worms. Our study provides mechanistic
      insights into the beneficial effects of metformin on human cellular aging and
      highlights the importance of the Nrf2-GPx7 pathway in pro-longevity signaling.

PMID- 29659169
TI  - Single nucleotide variant counts computed from RNA sequencing and cellular
      traffic into human kidney allografts.
AB  - Advances in bioinformatics allow identification of single nucleotide
      polymorphisms (variants) from RNA sequence data. In an allograft biopsy, 2
      genomes contribute to the RNA pool, 1 from the donor organ and the other from the
      infiltrating recipient's cells. We hypothesize that imbalances in genetic
      variants of RNA sequence data of kidney allograft biopsies provide an objective
      measure of cellular infiltration of the allograft. We performed mRNA sequencing
      of 40 kidney allograft biopsies, selected to represent a comprehensive range of
      diagnostic categories. We analyzed the sequencing reads of these biopsies and of
      462 lymphoblastoid cell lines from the 1000 Genomes Project, for RNA variants.
      The ratio of heterozygous to nonreference genome homozygous variants (Het/Hom
      ratio) on all autosomes was determined for each sample, and the estimation of
      stromal and immune cells in malignant tumors using expression data (ESTIMATE)
      score was computed as a complementary estimate of the degree of cellular
      infiltration into biopsies. The Het/Hom ratios (P = .02) and the ESTIMATE scores
      (P < .001) were associated with the biopsy diagnosis. Both measures correlated
      significantly (r = .67, P < .0001), even though the Het/Hom ratio is based on
      mRNA sequence variation, while the ESTIMATE score uses mRNA expression. Het/Hom
      ratio and the ESTIMATE score may offer unbiased and quantitative parameters for
      characterizing cellular traffic into human kidney allografts.

PMID- 29659170
TI  - Association of peripheral blood leukocyte KIBRA methylation with gastric cancer
      risk: a case-control study.
AB  - KIBRA was reported to be involved in various types of cancer and can be detected
      in blood. The purpose of this study was to investigate the relationship between
      the status of KIBRA methylation in peripheral blood leukocytes and gastric cancer
      (GC) risk. A case-control study was carried out to evaluate the association of
      blood cell-derived KIBRA methylation with the risk of GC using methylation
      sensitive high-resolution melting analysis. A total of 393 cases and 393 controls
      were detected, respectively. Compared with the subjects in the KIBRA negative
      methylation (NM) group, positive methylation (PM) subjects exhibited a 1.52-fold
      (95% CI: 1.030-2.251, P = 0.035) increased risk for GC. Stratified analyses
      demonstrated that the significant association of KIBRA methylation with GC risk
      existed in the older group (>= 60 years; ORa  = 1.846, 95% CI: 1.037-3.287, P =
      0.037) and Helicobacter pylori (H. pylori) positive subjects (ORa  = 1.933, 95%
      CI: 1.103-3.386, P = 0.021). Statistically significant combination effects
      between the environmental factors and KIBRA methylation on the GC risk were
      observed except for storing food under refrigeration. KIBRA methylation derived
      from blood cells and combinations thereof with environmental factors may be
      associated with the risk of GC.

PMID- 29659172
TI  - Optic disc drusen: understanding an old problem from a new perspective.
AB  - Optic disc drusen (ODD) are acellular deposits located in the optic nerve head of
      up to 2.4% of the population. They may develop as by-products of impaired axonal
      metabolism in genetically predisposed individuals, in whom a narrow scleral canal
      is hypothesized to play a role. Although ODD are often considered as benign
      innocent bystanders, recognized as part of a routine ophthalmological
      examination, the vast majority of patients with ODD have visual field defects.
      Optic disc drusen (ODD)-associated complications with severe visual loss, most
      often due to anterior ischaemic optic neuropathy, are also known to occur. There
      are no treatments available to prevent or ameliorate the vision loss caused by
      ODD. In children, the ODD are usually uncalcified and buried within the optic
      nerve head tissue. In these cases, the condition can be difficult to diagnose, as
      it often resembles a papilloedema with optic nerve head swelling caused by raised
      intracranial pressure. During the teenage years, the ODD progressively become
      more calcified and probably also larger, which allow them to be visible on
      ophthalmoscopy. With the advent and proper utilization of high-resolution
      modalities of optical coherence tomography (OCT), it has now become possible to
      detect even the smallest and most deeply located ODD. This allows for ODD
      detection at a much earlier developmental stage than has previously been possible
      and enhances the possibilities of research in underlying mechanisms. A review of
      the literature on ODD was conducted using the PUBMED database. The review focuses
      on the current knowledge regarding pathogenesis, diagnostics, clinical disease
      tracking methodologies, structure-function relationships and treatment strategies
      of ODD.

PMID- 29659171
TI  - Lipin-1 determines lung cancer cell survival and chemotherapy sensitivity by
      regulation of endoplasmic reticulum homeostasis and autophagy.
AB  - Cancer cells undergo comprehensive metabolic reprogramming to meet the increased
      requirements of energy and building blocks for proliferation. Lipin-1, a
      phosphatidic acid phosphatase converting phosphatidic acid (PA) to diacylglycerol
      (DAG), is upregulated in lung adenocarcinoma (LUAD) cell lines and tumor tissues.
      In this study, we reveal high lipin-1 expression is correlated with poor
      prognosis of patients with LUAD. Knockdown of lipin-1 decreases cell viability
      and proliferation in LUAD cells, whereas it has less effect on nontumorigenic
      lung cells. Autophagy and ER stress play important roles in tumor initiation and
      progression. Lipin-1 knockdown induces the initiation of autophagy while disrupts
      formation of autolysosome. Lipin-1 silencing induces the activation of ER stress
      through the IRE1alpha pathway. Furthermore, we demonstrate disrupted ER
      homeostasis contributes to the cell phenotype, and the elevated autophagy
      initiation is due to the ER stress in part. For the first time, we show lack of
      lipin-1 enhances the sensitivity of LUAD cells to cisplatin treatment. Our
      results suggest that lipin-1 is a potential target, alone or combined with other
      treatment, for lung cancer therapy.

PMID- 29659173
TI  - Usefulness of CD200 in the differential diagnosis of SDRPL, SMZL, and HCL.

PMID- 29659174
TI  - Water-Soluble Phospholo[3,2-b]phosphole-P,P'-Dioxide-Based Fluorescent Dyes with
      High Photostability.
AB  - We recently reported that fluorescent dye PB430, which consisted of a 2-phenyl
      substituted benzophosphole P-oxide skeleton that was reinforced by a methylene
      bridge, showed pronounced photostability and, thus, high utility for applications
      in super-resolution stimulated emission depletion (STED) microscopy. Herein, we
      replaced the methylene bridge with another P=O group to 1) investigate the role
      of the bridging moieties; and 2) further modulate the fluorescence properties of
      this skeleton. We synthesized a series of phospholo[3,2-b]phosphole-based dyes
      trans-PO-PB430, cis-PO-PB430, and trans-PO-PB460-all of which showed sufficient
      water solubility. Moreover, trans-PO-PB430 and trans-PO-PB460 exhibited intense
      green and orange fluorescence, respectively, and a high photostability that was
      comparable to that of PB430. In contrast, cis-PO-PB430 underwent rapid
      photobleaching upon continuous photoirradiation, which demonstrated the
      importance of steric shielding of the polycyclic skeleton by the substituents on
      the bridging moieties. The fluorescence properties of these dyes were insensitive
      to concentration, pH value, and polarity changes of the environment in solution.
      In addition, even in the solid state, these dyes showed strong green to orange
      emissions. These results demonstrate the potential utility of trans-PO-PB430 and
      trans-PO-PB460 as highly photostable fluorescent dyes.

PMID- 29659175
TI  - Extracranial Course of the Facial Nerve Revisited.
AB  - INTRODUCTION: The extrapetrous course of the facial nerve has been a matter of
      study and debate since XIX century. Two different classifications have been
      classically proposed and widely accepted by most of the authors. Nevertheless,
      there are reported cases which do not fit in any of those. The aim of this study
      is to propose a new and useful classification. MATERIAL AND METHODS: We have used
      23 embalmed Caucasian adult cadavers (11 male and 12 female) belonging to the
      Bodies Donation and Dissecting Rooms Centre of the University Complutense of
      Madrid. The extra-petrous facial nerve was dissected in the possible specimens
      resulting in 38 facial nerves. The studied parameters were length, diameter of
      divisions, terminal branches, and nerve connections. RESULTS: In every specimen
      two main divisions were found, temporofacial and cervicofacial. They divided into
      five terminal branches from cranial to caudal: temporal, zygomatic, buccal,
      marginal or mandibular, and cervical. Based on the comparison with previous
      proposed classifications, we have unified the patterns in 12 types being the most
      frequent types the type 3 (eight cases, 21.05%), with connections between
      temporal, zygomatic and buccal branches and the type 8 (eight cases, 21.05%), a
      complex network between temporal, zygomatic, buccal, and mandibular branches. The
      number of terminal branches was so variable. CONCLUSION: We propose a new 12
      patterned classification which summarizes the previous ones. However, we consider
      that a good study of the number of terminal branches, connections between
      branches or with other cranial nerves are more useful for surgeons to avoid
      injuries to the facial nerve during surgery than complex classifications. Anat
      Rec, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29659176
TI  - Nrf2 attenuates inflammatory response in COPD/emphysema: Crosstalk with
      Wnt3a/beta-catenin and AMPK pathways.
AB  - Chronic obstructive pulmonary disease (COPD) is characterized by persistent
      airflow limitation and abnormal inflammatory response. Wnt/beta-catenin and AMP
      activated protein kinase (AMPK) have been shown to modulate lung inflammatory
      responses and injury. However, it remains elusive whether Wnt/beta-catenin and
      AMPK modulate nuclear factor erythroid-2 related factor-2 (Nrf2)-mediated
      protective responses during the development of emphysema. Here we showed that
      treatment with a Wnt pathway activator (LiCl) reduced elastase-induced airspace
      enlargement and cigarette smoke extract (CSE)-induced lung inflammatory responses
      in WT mice, which was associated with increased activation of Nrf2 pathway.
      Interestingly, these effects of LiCl were not observed in Nrf2-/- mice exposed to
      elastase. In normal human bronchial epithelial (NHBE) cells, Wnt3a overexpression
      up-regulated, whereas Wnt3a knockdown further down-regulated the levels of Nrf2
      and its target proteins heme oxygenase-1 (HO-1) and NAD(P)H: quinone
      oxidoreductase 1 (NQO1) by CSE treatment. In contrast, Nrf2 deficiency did not
      have any effects on Wnt/beta-catenin pathway in mouse lungs and NHBE cells. Both
      elastase and CSE exposures reduced AMPK phosphorylation. A specific AMPK
      activator metformin increased Wnt3a, beta-catenin, Nrf2 phosphorylation and
      activation but reduced the levels of IL-6 and IL-8 in NHBE cells and mouse lungs
      exposed to CSE. Furthermore, Nrf2 deficiency abolished the protection of
      metformin against CSE-induced increase in IL-6 and IL-8 in NHBE cells. In
      conclusion, Nrf2 mediates the protective effects of both Wnt3a/beta-catenin and
      AMPK on lung inflammatory responses during the development of COPD/emphysema.
      These findings provide potential therapeutic targets for the intervention of
      COPD/emphysema.

PMID- 29659177
TI  - The Anatomical Relationships of the Ocular Motor Nerves with an Emphasis on
      Surgical Anatomy of the Orbit.
AB  - The surgical procedures directed to the orbit are invariably reported to be one
      of the most challenging procedures of the neurosurgery and it is very important
      to take measures to protect the ocular nerves. Many researchers have tried to
      identify safe approaches or safe regions in the orbit but the suggestions and
      results vary among published studies. The ocular motor nerves are under risk of
      injury during various approaches to the orbit. Simple but careful attention to
      potential variations in the origin and anatomical course of the ocular nerves and
      their relationships to the orbit may help to define "safe zones" during various
      approaches, thus, help to enhance clinical outcomes. The objective of this
      review, therefore, is to discuss the surgical anatomy of the orbit with special
      emphasis on oculomotor, trochlear, and abducens nerves and further emphasize
      their relationships with a surgical point of view during various approaches
      directed to the orbit. Anat Rec, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29659178
TI  - A Prospective Randomized, Double-Blind, Two-Period Crossover Pharmacokinetic
      Trial Comparing Green Coffee Bean Extract-A Botanically Sourced Caffeine-With a
      Synthetic USP Control.
AB  - Coffee is a primary dietary source of the chlorogenic acids (CGAs) of phenolic
      compounds. Coffee contains caffeine and other phytonutrients, including CGAs.
      Caffeine on its own has been well characterized and descried pharmacokinetically
      in the literature, less so for CGAs. The purpose of this double-blind crossover
      study was to determine the comparative pharmacokinetics of CGAs with caffeine
      (natural extract) with synthetic caffeine (US Pharmacopeia [USP] standard).
      Sixteen healthy male subjects were randomly assigned to take 1 dose of product 1,
      60 mg of botanically sourced caffeine from 480 mg of green coffee bean extract,
      or product 2, 60 mg of synthetic USP caffeine, with 5 days between. Blood
      analysis was done to determine the levels of CGA compounds, more specifically 3-,
      4-, and 5-caffeoylquinic acid (CQA), and serum caffeine. The natural caffeine
      extract exhibited mean peak concentrations (Cmax ) of 3-CQA (11.4 ng/mL), 4-CQA
      (6.84 ng/mL), and 5-CQA (7.20 ng/mL). The mean systemic 4-hour exposure (AUC0-4 h
      ) was 3-CQA (27.3 ng.h/mL), 4-CQA (16.1 ng.h/mL), and 5-CQA (15.7 ng.h/mL). The
      median tmax was 3-CQA (1.00 hour), 4-CQA (1.00 hour), and 5-CQA (1.50 hours). The
      tmax of caffeine was 0.75 hours (natural extract) and 0.63 hours (synthetic
      caffeine). Cmax and AUC0-4 h of serum caffeine were statistically equivalent
      between products. The geometric least-squares mean ratios (GMRs) of Cmax and AUC0
      4 h of caffeine were 97.77% (natural extract) and 98.33% (synthetic caffeine). It
      would appear that CGA compounds from the natural caffeine extract are
      bioavailable, and 3-CGA may be the compound most absorbed. In addition, caffeine
      sourced from natural extract versus synthetic were statistically similar for
      pharmacokinetic parameters. There were no adverse events or safety concerns.

PMID- 29659180
TI  - Envisioning Democracy: Participatory Filmmaking with Homeless Youth.
AB  - This paper explores the democratic potential for participatory filmmaking with
      homeless youth, as well as the constraints and dilemmas associated with this
      visual method. Theorizing democracy through the work of Hannah Arendt and Pierre
      Bourdieu, the paper approaches democracy not as an end, but rather as a process
      that seeks to lessen social injustice. Bourdieu's work helps us appreciate,
      however, that this process is constrained by structures of inequality that shape
      access to the political dispositions that enable such engagement. Consistent with
      other research on low-income and marginalized young people, this study found that
      homeless youth engage with democracy through forms of community participation and
      mutual support, and are disinclined to orient toward liberal democratic
      structures such as voting and political parties, which they see as harmful or
      problematic. With a focus on one particular dilemma faced by the research team
      namely, the question of how to make sense of and represent the issue of
      legalizing marijuana, which had been signaled by the youth participants as of
      primary political importance to them-the paper uses Arendt and Bourdieu to
      discuss how participatory filmmaking can help to expand the space of appearances
      available to homeless youth in Canadian society, and create a space at a shared
      table of understanding with middle class power brokers.

PMID- 29659181
TI  - Combination of anginex gene therapy and radiation decelerates the growth and
      pulmonary metastasis of human osteosarcoma xenografts.
AB  - Investigate whether rAAV-anginex gene therapy combined with radiotherapy could
      decrease growth and pulmonary metastasis of osteosarcoma in mice and examine the
      mechanisms involved in this therapeutic strategy. During in vitro experiment,
      multiple treatment regimes (rAAV-eGFP, radiotherapy, rAAV-anginex, combination
      therapy) were applied to determine effects on proliferation of endothelial cells
      (ECs) and G-292 osteosarcoma cells. During in vivo analysis, the same multiple
      treatment regimes were applied to osteosarcoma tumor-bearing mice. Use
      microcomputed tomography to evaluate tumor size. Eight weeks after tumor cell
      inoculation, immunohistochemistry was used to assess the therapeutic efficacy
      according to microvessel density (MVD), proliferating cell nuclear antigen
      (PCNA), and terminal-deoxynucleotidyl transferase-mediated nick-end labeling
      (TUNEL) assays. Metastasis of lungs was also evaluated by measuring number of
      metastatic nodules and wet weight of metastases. The proliferation of ECs and the
      tumor volumes in combination therapy group were inhibited more effectively than
      the other three groups at end point (P < 0.05). Cell clone assay showed anginex
      had radiosensitization effect on ECs. Immunohistochemistry showed tumors from
      mice treated with combination therapy exhibited the lowest MVD and proliferation
      rate, with highest apoptosis rate, as confirmed by IHC staining for CD34 and PCNA
      and TUNEL assays (P < 0.05). Combination therapy also induced the fewest
      metastatic nodules and lowest wet weights of the lungs (P < 0.05). rAAV-anginex
      combined with radiotherapy induced apoptosis of osteosarcoma cells and inhibited
      tumor growth and pulmonary metastasis on the experimental osteosarcoma models. We
      conclude that the primary mechanism of this process may be due to sensitizing
      effect of anginex to radiotherapy.

PMID- 29659179
TI  - NK cell and Th17 responses are differentially induced in murine cytomegalovirus
      infected renal allografts and vary according to recipient virus dose and strain.
AB  - Human cytomegalovirus (HCMV) donor positive (D+) serostatus with acute rejection
      is associated with renal allograft loss, but the impact of recipient positive
      (R+) serostatus is unclear. In an allogeneic renal transplant model, antiviral
      natural killer (NK) and CD8+ T cell memory responses in murine CMV (MCMV) D+/R+
      transplants were compared to D-/R- and D+/R- transplants, with recipient
      infection varied by MCMV dose and strain. D+/R- transplants had high primary
      antiviral cytolytic (interferon-gamma+) and cytotoxic (granzyme B+) NK responses,
      whereas NK memory responses were lower in D+/R+ recipients receiving a high
      primary MCMV dose. Despite MCMV immunity, D+/R+ recipients receiving a low MCMV
      dose showed primary-like high cytolytic and cytotoxic NK responses. D+/R+
      transplants infected with different D/R strains had low cytolytic NK responses
      but high cytotoxic NK responses. NK memory also induced a novel TNF-alpha+ NK
      response among high-dose virus recipients. MCMV+ transplants had greater Th17
      responses than MCMV-uninfected transplants and Th17 inhibition ameliorated graft
      injury. All MCMV+ recipients had similar CD8+ T cell responses. In sum, NK and
      Th17 responses, but not CD8+ T cells, varied according to conditions of primary
      recipient infection. This variability could contribute to variable graft outcomes
      in HCMV D+/R+ renal transplantation.

PMID- 29659182
TI  - Ropivacaine Wound Infiltration for Pain Management After Breast Cancer
      Mastectomy: A Population Pharmacokinetic Analysis.
AB  - Ropivacaine continuous wound infusions (CWIs) are extensively used as a component
      of multimodal analgesia. The rational application of CWI of ropivacaine requires
      a thorough understanding of its pharmacokinetics to investigate the risk of
      potential systemic toxicity. A population pharmacokinetic (popPK) study was
      undertaken to describe the pharmacokinetics of ropivacaine CWI during 75 hours.
      Women undergoing a unilateral mastectomy were scheduled to receive CWI for 40
      hours for postoperative analgesia. A 10-mL ropivacaine 0.75% bolus followed by
      continuous infusion (400 mL of 0.2% ropivacaine at a flow rate of 10 mL/h) was
      administered via a multihole catheter placed on the major pectoral muscle. PopPK
      analysis was performed using the nonlinear mixed-effects model. A 1-compartment
      disposition model with an absorption compartment and a transit compartment for
      the infusion best describes the data (67 observations from 10 women). Population
      parameter estimates (between-subject variability, %) are apparent central volume
      (V/F) 269 L (39.1%), apparent clearance (CL/F) 18.8 h-1 (74.9%), and absorption
      rate (K12) 0.406 h-1 . The model predicted Cmax as 1.45 +/- 0.80 MUg/mL, which
      occurred in the 42.4th hour (39-45.9 hours). This popPK model describes the
      pharmacokinetics of ropivacaine during continuous wound infusion and confirms the
      safety profile of the present technique.

PMID- 29659183
TI  - Predictors of visual outcomes in patients with neovascular age-related macular
      degeneration treated with anti-vascular endothelial growth factor therapy: post
      hoc analysis of the VIEW studies.
AB  - PURPOSE: Identify predictors for response to anti-vascular endothelial growth
      factor (VEGF) therapy in patients with neovascular (wet) age-related macular
      degeneration (nAMD). METHODS: Retrospective, post hoc analysis of VIEW 1/2.
      Patients were randomized 1:1:1:1 to 0.5 mg intravitreal aflibercept (IVT-AFL)
      injection every 4 weeks (0.5q4); 2 mg IVT-AFL every 4 weeks (2q4); 2 mg IVT-AFL
      every 8 weeks (2q8) after an initial three injections at weeks 0, 4 and 8 or 0.5
      mg intravitreal ranibizumab every 4 weeks (0.5q4). RESULTS: 1815 patients [IVT
      AFL 2q4 (n = 613); IVT-AFL 2q8 (n = 607); ranibizumab 0.5q4 (n = 595)] were
      included. Baseline demographics/characteristics were evenly balanced. Younger age
      (49-69 years), lower visual acuity (VA) [10.0-<=45.0 Early Treatment Diabetic
      Retinopathy Study (ETDRS) letters] and smaller choroidal neovascularization (CNV)
      size [0.0-<=3.1 disc areas (DA)] at baseline were associated with the most vision
      gain (>=15 letters) over 52 weeks (all nominal p < 0.0001).Younger age, higher
      baseline VA (>64.0-<=83.0 letters) and smaller CNV size were associated with a VA
      >=20/40 at week 52. Predominantly classic CNV at baseline (nominal p = 0.0007),
      older age (>=90 years), lower baseline VA (10.0-<= 45.0 ETDRS letters) and larger
      CNV size (>10.1-<=32.6 DA) were all associated with a VA <=20/200 at week 52 (all
      nominal p < 0.0001). Along with treatment (nominal p < 0.0001), lower VA (p =
      0.0166) and smaller central retinal thickness (both nominal p = 0.0190) were
      predictors for dry retina development. CONCLUSION: Younger age, lower VA and
      smaller CNV size at baseline were all associated with greater vision gains over
      52 weeks while younger age, higher VA and smaller CNV size at treatment start
      were more likely to achieve best-corrected VA 20/40 or better after a year's
      treatment, suggesting the benefit of early anti-VEGF treatment.

PMID- 29659184
TI  - The Human Laryngeal Innervation Revisited. The Role of the Neural Connections.
AB  - In spite that vascular inconvenients or immunological rejections have been solved
      in relation with larynx transplant, a successful functional reinnervation has not
      been achieved. Some studies have suggested that laryngeal nerve connection may
      contain motor fibers, which could explain unexpected evoked responses in
      electromyographic studies or the different positions adopted of the vocal folds
      after similar nerve lesions. Ten patients with unexpected evoked responses after
      laryngeal nerve stimulation were selected. All the patients underwent a total
      laryngectomy due to oncological causes. In every case, laryngeal nerve
      connections were observed. All of them were morphologic and histologic processed
      for choline-acetyltransferase immunohistochemistry. The presence of motor axons
      in the nerve connections has been demonstrated, which would explain that the
      motor innervation to the laryngeal muscles could be dual through these variable
      connections. This also would justify the difficulty of carrying out laryngeal
      nerve reinnervation procedures. Anat Rec, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29659185
TI  - The Cochlear Spiral Ganglion Neurons: The Auditory Portion of the VIII Nerve.
AB  - The VIII nerve is formed by sensory neurons that innervate the inner ear, i.e.,
      the vestibular and the auditory receptors. Neurons of the auditory portion, the
      cochlear afferent fibers that innervate the sensory hair cells of the organ of
      Corti, have their somas in the cochlear spiral ganglion where two types of
      neurons can be distinguished. Afferent Type-I neurons are the 95% of the total
      population. Bipolar and myelinated fibers, each one innervates only one cochlear
      inner hair cell (IHC). In contrast, afferent Type-II neurons are only the 5% of
      the spiral ganglion population. They are pseudounipolar and unmyelinated fibers
      and innervate the cochlear outer hair cells (OHC) so that one afferent Type-II
      fiber contacts with multiple OHCs, but each OHC only receives one contact from
      one Type-II neuron. Both types of VIII nerve fibers are glutamatergic, but these
      asymmetric innervations of the cochlear sensory cells could suggest that the IHC
      codifies the truly auditory message but the OHC only informs about mechanical
      aspects of the state of the organ of Corti. In fact, the central nervous system
      (CNS) has control over the information transmitted by the Type-I neuron by means
      of axons from the superior olivary complex that innervate them to modulate,
      filter and/or inhibit the entry of auditory message to CNS. The aim of this paper
      is to review the current knowledge about the anatomy and physiology of the
      auditory portion of the VIII nerve. Anat Rec, 2018. (c) 2018 Wiley Periodicals,
      Inc.

PMID- 29659186
TI  - Nursing Outcomes for Patients with Risk of Perioperative Positioning Injury.
AB  - PURPOSE: To select and refine the outcomes and indicators of Nursing Outcomes
      Classification for the diagnosis of risk for perioperative positioning injury.
      METHOD: Validation study on expert consensus and refinement through pilot study.
      FINDINGS: Eight outcomes and 35 indicators were selected in consensus. After
      clinical testing was performed, in which 10 patients were assessed at five
      different times. Eight outcomes and 33 indicators remained in the protocol.
      CONCLUSION: This study made it possible to select the most relevant outcomes and
      indicators to be measured for this diagnosis in clinical practice. IMPLICATIONS
      FOR NURSING PRACTICE: Validation studies by consensus and clinical testing are
      important to promote the accuracy, creating opportunities to legitimize, and
      improve the concepts of taxonomies.

PMID- 29659188
TI  - Dissecting through barriers: A follow-up study on the long-term effects of
      interprofessional education in a dissection course with healthcare professional
      students.
AB  - Several studies have shown significant improvements in the attitudes and
      perceptions of healthcare professional students toward interprofessional
      education (IPE) immediately following intervention with IPE courses. However,
      there remains little evidence on the lasting effects of IPE courses and the long
      term influences of these IPE experiences are poorly documented. The purpose of
      this study is to assess the long-term effects of an intensive, ten-week
      interprofessional gross anatomy dissection course at McMaster University.
      Attitudes and perceptions of past participants towards interprofessional learning
      were evaluated, now that they have started working with other healthcare
      professionals outside of the IPE course setting. Thirty-four past participants
      who have clinical experience working in interprofessional settings or are
      currently working in the healthcare field completed a follow-up questionnaire
      consisting of a modified Readiness for Interprofessional Learning Scale (RIPLS)
      and open-ended questions. Quantitative analysis revealed a significant decrease
      in their attitude towards teamwork and collaboration and respect for other health
      professions, but a significant improvement in their understanding of roles and
      responsibilities compared to their results immediately after the IPE
      intervention. Qualitative analysis of open-ended questions revealed several
      themes such as developing interprofessional competencies, developing
      relationships, and remembering the strengths of the IPE dissection course. The
      results of this study indicate that the IPE experience in anatomy was highly
      valued by the students and that past participants maintain a clear understanding
      of their scope of practice, but the reality of clinical practice may have eroded
      gains made in the program. Anat Sci Educ. (c) 2018 American Association of
      Anatomists.

PMID- 29659187
TI  - Bioequivalence of Oral Formulations of Anastrozole in Healthy Chinese Male
      Volunteers: A Randomized, Single-Dose, Two-Period, Two-Sequence Crossover Study.
AB  - Anastrozole is currently used as first-line treatment in locally advanced or
      metastatic breast cancer. A generic anastrozole tablet was developed to offer an
      alternative to the marketed tablet formulation. The aim of the current study was
      to evaluate the bioequivalence between the test and reference formulations of
      anastrozole in a single-dose, 2-period, 2-sequence crossover study with a 14-day
      washout interval. A total of 20 healthy male Chinese volunteers were enrolled and
      completed the study, after oral administration of a single dose of 1.0-mg test
      and reference formulations of anastrozole. The blood samples were collected at
      different times and were determined by a fully validated high-pressure liquid
      chromatography-tandem mass spectrometry method. The evaluated pharmacokinetic
      parameters, including Cmax , AUC0-t , and AUC0-infinity , were assessed for
      bioequivalence based on current guidelines. The observed pharmacokinetic
      parameters of anastrozole of the test drug were similar to those of the reference
      formulation. The 90% confidence intervals of test/reference ratios for Cmax ,
      AUC0-t , and AUC0-infinity were within the bioequivalence acceptance range of 80%
      125%. The results obtained from these healthy Chinese subjects in this study
      suggest that the test formulation of anastrozole 1.0-mg tablet is bioequivalent
      to the reference formulation (Arimidex 1.0-mg tablet).

PMID- 29659189
TI  - The effect of tea consumption on the steroid profile.
AB  - Green tea (GT), along with its flavonol epigallocatechin-3-gallate (EGCG), has
      shown to inhibit the UGT2B17 isoenzyme, which is highly involved in the
      glucuronidation of testosterone (T) and its metabolites. Since the steroid
      profile (SP) is composed of urinary concentrations of T and related metabolites
      excreted in both the free and the glucuronide fractions, GT consumption could
      alter the SP, leading to misunderstanding in doping controls. The aim of the
      present work was to study the effect of GT consumption on the SP. This study was
      performed with 29 male volunteers, which could be classified in 2 arms depending
      on their T/E values (0.12 +/- 0.02, n = 12; 1.64 +/- 0.90, n = 17). The clinical
      protocol was designed to evaluate the effect of GT administration on the SP
      biomarkers. Participants were asked to consume GT with a high content of EGCG for
      7 days (5 GT beverages along the whole day for days 1-6 and 9 GT beverages on day
      7, corresponding to 520 and 936 mg/day of EGCG, respectively). Urine samples were
      collected before and during GT consumption at different time periods. The SP was
      measured using gas chromatography-mass spectrometry. The excretion rates of the
      SP metabolites did not change after GT consumption. Moreover, the individual
      evaluation of the subject's steroidal biological passport resulted in normal
      sequences. The results obtained show that GT consumption does not distort the
      establishment of normal ranges of SP parameters. Therefore, GT consumption does
      not need to be considered a confounding factor in the SP evaluation.

PMID- 29659190
TI  - Light-Induced Buckles Localized by Polymeric Inks Printed on Bilayer Films.
AB  - Buckling instabilities generate microscale features in thin films in a facile
      manner. Buckles can form, for example, by heating a metal/polymer film stack on a
      rigid substrate. Thermal expansion differences of the individual layers generate
      compressive stress that causes the metal to buckle over the entire surface. The
      ability to dictate and confine the location of buckle formation can enable
      patterns with more than one length scale, including hierarchical patterns. Here,
      sacrificial "ink" patterned on top of the film stack localizes the buckles via
      two mechanisms. First, stiff inks suppress buckles such that only the non-inked
      regions buckle in response to infrared light. The metal in the non-inked regions
      absorbs the infrared light and thus gets sufficiently hot to induce buckles.
      Second, soft inks that absorb light get hot faster than the non-inked regions and
      promote buckling when exposed to visible light. The exposed metal in the non
      inked regions reflects the light and thus never get sufficiently hot to induce
      buckles. This second method works on glass substrates, but not silicon
      substrates, due to the superior thermal insulation of glass. The patterned ink
      can be removed, leaving behind hierarchical patterns consisting of regions of
      buckles among non-buckled regions.

PMID- 29659193
TI  - Pharmacologic and Pharmacodynamic Equivalence of 2 Formulations of Orlistat.
AB  - We sought to establish the bioequivalence of 2 weight-loss aids: orlistat 27-mg
      chewable tablet and orlistat 60-mg capsule, measured pharmacodynamically as
      percentage fecal fat excretion. Two open-label, single-center, randomized, 3
      period, 3-treatment crossover studies were conducted in adults with body mass
      index 25-33 kg/m2 . For each 9-day treatment period, subjects received orlistat
      27-mg chewable tablet, 60-mg capsule, or 120-mg capsules (2 60-mg capsules) 3
      times daily; a 2-day washout separated treatments. Primary bioequivalence
      analyses were based on 2 1-sided tests of the 90% CI of the ratio of geometric
      means using log-transformed data (study 1) and by the dose-scale method to
      calculate bias-corrected and accelerated 90% CI of relative bioavailability (f)
      using nontransformed data (study 2). Bioequivalence was established if 90% CIs
      fell within 0.80-1.25. In total, 48 and 144 subjects were randomized in study 1
      and study 2, respectively. Bioequivalence between the formulations was
      established in both studies: study 1 ratio of geometric means of percentage fecal
      fat excretion was 0.96 (2 1-sided tests, 90% CI 0.87-1.06); study 2-point
      estimate of f was 1.09 (bias-corrected and accelerated 90% CI 0.98-1.22).
      Tolerability of the 27-mg tablet was consistent with the 60-mg capsule; mild
      gastrointestinal effects were most common.

PMID- 29659191
TI  - Optimised ARID1A immunohistochemistry is an accurate predictor of ARID1A
      mutational status in gynaecological cancers.
AB  - ARID1A is a tumour suppressor gene that is frequently mutated in clear cell and
      endometrioid carcinomas of the ovary and endometrium and is an important clinical
      biomarker for novel treatment approaches for patients with ARID1A defects.
      However, the accuracy of ARID1A immunohistochemistry (IHC) as a surrogate for
      mutation status has not fully been established for patient stratification in
      clinical trials. Here we tested whether ARID1A IHC could reliably predict ARID1A
      mutations identified by next-generation sequencing. Three commercially available
      antibodies - EPR13501 (Abcam), D2A8U (Cell Signaling), and HPA005456 (Sigma) -
      were optimised for IHC using cell line models and human tissue, and screened
      across a cohort of 45 gynaecological tumours. IHC was scored independently by
      three pathologists using an immunoreactive score. ARID1A mutation status was
      assessed using two independent sequencing platforms and the concordance between
      ARID1A mutation and protein expression was evaluated using Receiver Operating
      Characteristic statistics. Overall, 21 ARID1A mutations were identified in 14/43
      assessable tumours (33%), the majority of which were predicted to be deleterious.
      Mutations were identified in 6/17 (35%) ovarian clear cell carcinomas, 5/8 (63%)
      ovarian endometrioid carcinomas, 2/5 (40%) endometrial carcinomas, and 1/7 (14%)
      carcinosarcomas. ROC analysis identified greater than 95% concordance between
      mutation status and IHC using a modified immunoreactive score for all three
      antibodies allowing a definitive cut-point for ARID1A mutant status to be
      calculated. Comprehensive assessment of concordance of ARID1A IHC and mutation
      status identified EPR13501 as an optimal antibody, with 100% concordance between
      ARID1A mutation status and protein expression, across different gynaecological
      histological subtypes. It delivered the best inter-rater agreement between all
      pathologists, as well as a clear cost-benefit advantage. This could allow
      patients to be accurately stratified based on their ARID1A IHC status into early
      phase clinical trials.

PMID- 29659192
TI  - Ruthenium(II)-Bipyridine/NanoC3 N4 Hybrids: Tunable Photochemical Properties by
      Using Exchangeable Alkali Metal Cations.
AB  - A series of nanoporous carbon nitrides that contained a range of alkali metal
      cations (M@nanoC3 N4 : M=Li+ , Na+ , K+ , Rb+ , and Cs+ ) have been successfully
      synthesized from as-synthesized g-C3 N4 by delamination with concentrated
      sulfuric acid, followed by neutralization with aqueous solutions of the
      corresponding alkali metal hydroxides. Tris(2,2'-bipyridine)ruthenium(II)
      complexes, [Ru(bpy)3 ]2+ , were grafted onto the carbon nitrides in an effort to
      explore the physicochemical properties of the deposited [Ru(bpy)3 ]2+ , as well
      as its photocatalytic activity in the aerobic photooxidation of phenylboronic
      acid and H2 production from aqueous media in the presence of a Pt co-catalyst
      under visible-light irradiation. Highly porous nanoC3 N4 could significantly
      enhance photocatalytic activity, because of its high surface area, owing to its
      unique porous structure. More interestingly, the photoluminescence intensities of
      [Ru(bpy)3 ]2+ complexes that were associated with M@nanoC3 N4 increased in the
      presence of lighter alkali metal cations, which correlated with increased
      photocatalytic activities for both reactions. This study demonstrates that
      M@nanoC3 N4 are fascinating supports, in which the local environment of an
      immobilized metal complex can be precisely controlled by varying the alkali metal
      cation from Li+ to Cs+ .

PMID- 29659194
TI  - Detection of hepatitis E virus RNA in saliva for diagnosis of acute infection.
AB  - Diagnosis of acute hepatitis E virus (HEV) infection is established by detection
      of anti-HEV IgM antibodies by ELISA or by amplification of serum viral RNA. Here,
      we evaluate the diagnostic value of testing HEV RNA in saliva to identify
      patients with acute HEV infection. Prospective proof-of-concept study including
      patients with acute hepatitis. Whole blood and neat saliva samples were obtained
      from all patients. Saliva samples were processed and analysed for HEV RNA by RT
      PCR within 2 hr after collection. A total of 34 patients with acute hepatitis and
      12 healthy donors were included in the study. HEV RNA in serum was confirmed by
      RT-PCR in eight of these patients (23.5%; 95% CI: 12.2%-40.2%). HEV was isolated
      in the saliva of eight of 34 patients (23.5%; 95% CI: 12.2%-40.2%). All patients
      with HEV RNA amplified in saliva had detectable HEV RNA in serum. HEV was
      isolated neither in the saliva of any of the 26 patients without detectable HEV
      RNA in serum nor in healthy donors. Our study suggests that acute HEV infection
      could be diagnosed by assessing viral load in saliva.

PMID- 29659195
TI  - miR-541 suppresses proliferation and invasion of squamous cell lung carcinoma
      cell lines via directly targeting high-mobility group AT-hook 2.
AB  - An increasing number of studies have demonstrated that micro-ribonucleic acids
      (miRNAs) are important tumor suppressors during carcinogenesis. However, the
      function of miRNA-541 (miR-541) in malignancies, especially lung cancer, has not
      been widely reported. In this study, miR-541 expression was significantly
      decreased in squamous cell lung carcinoma (SCLC) cancerous tissue and SCLC cell
      lines. To analyze miR-541 function in SCLC, we overexpressed miR-541 in SCLC cell
      lines (SK-MES-1 and H226). According to the CCK8, wound scratch, and transwell
      invasion assay results, miR-541 overexpression significantly inhibited SCLC cell
      proliferation, migration, and invasion ability. Next, using RT-PCR, Western
      blotting, immunocytochemistry, and luciferase assays, HMGA2 was identified, for
      the first time, as a direct regulatory target of miR-541 in SK-MES-1 and H226
      cells. Furthermore, upregulating HMGA2 expression significantly alleviated the
      suppressive effects of miR-541 on SK-MES-1 and H226 cell proliferation,
      migration, and invasion. In summary, our study revealed that miR-541 inhibited
      SCLC proliferation and invasion by directly targeting HMGA2.

PMID- 29659196
TI  - Lessons from Amphioxus Bauplan About Origin of Cranial Nerves of Vertebrates That
      Innervates Extrinsic Eye Muscles.
AB  - Amphioxus is the living chordate closest to the ancestral form of vertebrates,
      and in a key position to reveal essential aspects of the evolution of the brain
      Bauplan of vertebrates. The dorsal neural cord of this species at the larval
      stage is characterized by a small cerebral vesicle at its anterior end and a
      large posterior region. The latter is comparable in some aspects to the hindbrain
      and spinal cord regions of vertebrates. The rostral end of the cerebral vesicle
      contains a median pigment spot and associated rows of photoreceptor and other
      nerve cells; this complex is known as "the frontal eye." However, this is not a
      complete eye in the sense that it has neither eye muscles nor lens (only a
      primitive retina-like tissue). Cranial nerves III, IV, and VI take part in the
      motor control of eye muscles in all vertebrates. Using a recent model that
      postulates distinct molecularly characterized hypothalamo-prethalamic and
      mesodiencephalic domains in the early cerebral vesicle of amphioxus, we analyze
      here possible scenarios for the origin from the common ancestor of
      cephalochordates and vertebrates of the cranial nerves related with extrinsic eye
      muscle innervations. Anat Rec, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29659197
TI  - Morphological Features of the Branching Pattern of the Hypoglossal Nerve.
AB  - The hypoglossal or twelfth cranial nerve is the motor nerve to the extrinsic and
      intrinsic muscles of the tongue, and the superior root of the ansa cervicalis and
      the thyrohyoid and geniohyoid branches are delivered through the nerve. This
      study investigated the muscular branches of the hypoglossal nerve to clarify
      their spatial relationships with the muscles of the tongue and the neighboring
      structures. The muscles and the nerve were gross anatomically examined in 42
      cadavers. The superior root and the thyrohyoid branch left the nerve near the
      occipital and lingual arteries, respectively. The extrinsic muscles consisted of
      some components, and the geniohyoid branch and the lingual branches arose on the
      hyoglossus. The ascending lingual branches formed a plexus on the anterior part
      of the hyoglossus and were divided into the proximal and distal groups. They
      supplied the two parts of the hyoglossus, the three bundles of the styloglossus
      and the superior and inferior longitudinal muscles and communicated with the
      lingual nerve. The descending lingual branches supplied the inferior part of the
      genioglossus, and the terminal branches gave intramuscular twigs to its main part
      and the transverse and vertical muscles. The findings indicated that the
      branching pattern of the hypoglossal nerve is characterized by the positional
      relationships to the components of the extrinsic muscles. The hyoid bone can be
      an effective marker to identify the branches and affected position if it was used
      in combination with the morphology of the extrinsic muscles, and the knowledge of
      their variations is also beneficial. Anat Rec, 2018. (c) 2018 Wiley Periodicals,
      Inc.

PMID- 29659198
TI  - In silico modeling of oxygen-enhanced MRI of specific ventilation.
AB  - Specific ventilation imaging (SVI) proposes that using oxygen-enhanced 1H MRI to
      capture signal change as subjects alternatively breathe room air and 100% O2
      provides an estimate of specific ventilation distribution in the lung. How well
      this technique measures SV and the effect of currently adopted approaches of the
      technique on resulting SV measurement is open for further exploration. We
      investigated (1) How well does imaging a single sagittal lung slice represent
      whole lung SV? (2) What is the influence of pulmonary venous blood on the
      measured MRI signal and resultant SVI measure? and (3) How does inclusion of
      misaligned images affect SVI measurement? In this study, we utilized two patient
      based in silico models of ventilation, perfusion, and gas exchange to address
      these questions for normal healthy lungs. Simulation results from the two healthy
      young subjects show that imaging a single slice is generally representative of
      whole lung SV distribution, with a calculated SV gradient within 90% of that
      calculated for whole lung distributions. Contribution of O2 from the venous
      circulation results in overestimation of SV at a regional level where major
      pulmonary veins cross the imaging plane, resulting in a 10% increase in SV
      gradient for the imaging slice. A worst-case scenario simulation of image
      misalignment increased the SV gradient by 11.4% for the imaged slice.

PMID- 29659199
TI  - Analysis of potential genes and pathways associated with the colorectal normal
      mucosa-adenoma-carcinoma sequence.
AB  - This study aimed to identify differentially expressed genes (DEGs) related to the
      colorectal normal mucosa-adenoma-carcinoma sequence using bioinformatics
      analysis. Raw data files were downloaded from Gene Expression Omnibus (GEO) and
      underwent quality assessment and preprocessing. DEGs were analyzed by the limma
      package in R software (R version 3.3.2). Gene Ontology (GO) enrichment analysis
      and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were
      performed with the DAVID online tool. In a comparison of colorectal adenoma (n =
      20) and colorectal cancer (CRC) stage I (n = 31), II (n = 38), III (n = 45), and
      IV (n = 62) with normal colorectal mucosa (n = 19), we identified 336 common
      DEGs. Among them, seven DEGs were associated with patient prognosis. Five
      (HEPACAM2, ITLN1, LGALS2, MUC12, and NXPE1) of the seven genes presented a
      sequentially descending trend in expression with tumor progression. In contrast,
      TIMP1 showed a sequentially ascending trend. GCG was constantly downregulated
      compared with the gene expression level in normal mucosa. The significantly
      enriched GO terms included extracellular region, extracellular space, protein
      binding, and carbohydrate binding. The KEGG categories included HIF-1 signaling
      pathway, insulin secretion, and glucagon signaling pathway. We discovered seven
      DEGs in the normal colorectal mucosa-adenoma-carcinoma sequence that was
      associated with CRC patient prognosis. Monitoring changes in these gene
      expression levels may be a strategy to assess disease progression, evaluate
      treatment efficacy, and predict prognosis.

PMID- 29659200
TI  - Atypical tuberous sclerosis complex presenting as familial renal cell carcinoma
      with leiomyomatous stroma.
AB  - We report an atypical tuberous sclerosis complex (TSC) phenotype presenting as
      familial multiple renal cell carcinomas (RCCs) with (angio)leiomyomatous stroma
      (RCCLS) (5/7 familial RCCs) on a background of multiple angiomyolipomas,
      hypopigmented skin macules, and absence of neurological anomalies. In the index
      case and three relatives, germline genetic testing identified a heterozygous TSC2
      missense pathogenic variant [c.2714 G > A, (p.Arg905Gln)], a rare TSC-associated
      alteration which has previously been associated with a milder TSC phenotype.
      Whole-exome sequencing of five RCCs from the index case and one RCC from his
      mother demonstrated either unique tumour-specific deleterious second hits in TSC2
      or significant allelic imbalance at the TSC2 gene locus (5/6 RCCs). This study
      confirms the key tumourigenic role of tumour-specific TSC2 second hits in TSC
      associated RCCs and supports the notion that RCCLS may be strongly related to
      abnormalities of the mTOR pathway.

PMID- 29659201
TI  - Evaluation of Eluxadoline Effect on Cardiac Repolarization.
AB  - This study evaluated the effects of eluxadoline, a mixed MU-opioid receptor (OR)
      and kappa-OR agonist and delta-OR antagonist, on cardiac repolarization. This
      evaluator-blinded, placebo- and positive-controlled, 4-period crossover study
      randomized healthy men and women to single oral doses of eluxadoline (therapeutic
      dose 100 mg or supratherapeutic dose 1000 mg), moxifloxacin 400 mg, or placebo.
      QT data were corrected using individual custom correction (QTcI). The primary
      endpoint was the change from baseline in QTcI intervals (DeltaQTcI) between
      eluxadoline and placebo (DeltaDeltaQTcI). An upper bound of the 95% confidence
      interval around DeltaDeltaQTcI of 10 milliseconds was considered clinically
      significant. Concentration-QTc data were analyzed using a repeated-measures,
      mixed-effects linear model. Sixty-four volunteers were treated, and 58 completed
      the study. Assay sensitivity was demonstrated with moxifloxacin (noted by
      DeltaDeltaQTcI of 11.94 milliseconds). The maximum DeltaDeltaQTcI for eluxadoline
      1000 mg was 4.10 milliseconds 1 hour postdose (1-sided 95% upper confidence
      bound, 5.81 milliseconds), and for eluxadoline 100 mg was 1.20 milliseconds at
      0.5 hours postdose (1-sided 95% upper confidence bound, 2.91 milliseconds).
      Primary DeltaDeltaQTcI results were confirmed using Fridericia's formula for QTc.
      Categorical, morphological, and concentration-QTc analyses were consistent with
      the primary and secondary findings. There were no significant gender effects on
      DeltaDeltaQTcI values. The most common adverse events were contact dermatitis and
      nausea (12.5% each) and dizziness (10.9%); adverse events were more frequent in
      the eluxadoline 1000 mg group. In conclusion, eluxadoline, at therapeutic or
      supratherapeutic doses, did not significantly prolong QT intervals, and was safe
      and generally well tolerated in this study population.

PMID- 29659202
TI  - Lamotrigine Rechallenge in Treatment-Resistant Bipolar Disorder.
AB  - Background: Although lamotrigine may be useful for treating patients with
      treatment-resistant bipolar disorder, some lamotrigine-associated adverse
      effects, including mild to moderate skin rash, may prevent the continuation of
      treatment. Methods: We investigated lamotrigine rechallenge for the treatment of
      bipolar disorder. The present study was based on retrospective chart review of
      outpatients with bipolar disorder (DSM-5 criteria) who visited the hospital's
      psychiatric department between July 2011 and August 2017. The review revealed 12
      patients with bipolar disorder who underwent lamotrigine rechallenge following
      lamotrigine discontinuation due to various adverse reactions, including skin
      rash. None of the patients showed Stevens-Johnson syndrome. All patients suffered
      from treatment-resistant bipolar disorder that was refractory to treatments other
      than lamotrigine. For each patient, the severity of the adverse reaction to
      lamotrigine was weighed against the potential for therapeutic benefit. Results:
      In 9 of 12 cases, a positive outcome of lamotrigine rechallenge was observed. In
      all cases with initial skin rash with very slow titration of lamotrigine,
      rechallenge was successful with no recurrence of the rash. In the 3 cases for
      which lamotrigine was unsuccessful, lamotrigine was discontinued owing to
      movement disorders, ie, oral dyskinesia and action tremor, and liver dysfunction,
      respectively. Conclusions: The present results suggest that lamotrigine
      rechallenge may be a viable option for treatment-resistant bipolar disorder.

PMID- 29659203
TI  - A Qualitative Study to Assess How Primary Care Versus Psychiatric Providers
      Evaluate and Treat Pediatric Patients With Irritability.
AB  - Objective: To determine how primary care versus specialist practitioners assess
      and treat school-aged children with irritability. Methods: Seventeen providers
      from family medicine, pediatrics, and psychiatry participated in in-depth
      interviews from June to August 2016 about the process they use to evaluate
      irritability. Data on demographic traits and measures of confidence were also
      collected. Results: Primary care (family medicine and pediatrics) participants
      expressed frustration over the lack of time and specialized knowledge they had to
      accurately assess children with irritability, even though they were often the
      first clinician consulted when problems arose. There were clear and sometimes
      contradictory differences between how practitioners with a general versus
      specialized practice assessed mental health status in the clinic setting. Input
      on treatment approaches revealed that medication prescription was more common by
      primary care participants, and therapy was preferred by the psychiatry
      participants. Conclusions: Overall, family medicine and pediatric practitioners
      were significantly less confident in their ability to evaluate mental health
      status, while child and adolescent psychiatry participants were supportive of
      having more initial triage and possible treatment occur at the primary care
      level, suggesting a need for more training about childhood irritability in the
      primary care setting.

PMID- 29659204
TI  - Rethinking the Approach to Veteran Suicides.

PMID- 29659205
TI  - Executive Function Predicts Antidepressant Treatment Noncompletion in Late-Life
      Depression.
AB  - OBJECTIVE: To examine whether executive function (EF) is associated with
      nonremission and noncompletion of antidepressant pharmacotherapy in older adults
      with depression. DESIGN: In this prospective study (July 2009 to May 2014), older
      adults (aged >= 60 years; n = 468) with a DSM-IV-defined major depressive episode
      diagnosed via structured interview received 12 weeks of venlafaxine extended
      release with the goal of achieving remission. A hypothesis was made that worse
      baseline EF would predict both nonremission and noncompletion (primary outcomes).
      Treatment-related factors, including side effects and nonadherence, were also
      studied. METHODS: Baseline EF, including response inhibition and set-shifting,
      was assessed with subtests of the Delis-Kaplan Executive Function System and the
      semantic fluency subtest of the Repeatable Battery for the Assessment of
      Neuropsychological Status (RBANS). Attention, immediate memory, delayed memory,
      visuospatial ability, and global cognition were also assessed with the RBANS.
      RESULTS: Of 468 participants, 96 (21%) failed to complete the treatment trial,
      191 (41%) completed and remitted, and 181 (39%) completed and did not remit.
      Univariate analyses indicated that some EFs (set-shifting and semantic fluency)
      and other cognitive variables (attention, immediate memory, visuospatial ability,
      and global cognition) predicted treatment noncompletion, whereas no cognitive
      variables predicted nonremission. In a multivariate logistic regression model,
      semantic fluency (P = .003), comorbid medical burden (P < .001), and early
      nonadherence (P < .001) were significant predictors of treatment noncompletion.
      CONCLUSIONS: Poorer EF predicted treatment noncompletion. These findings suggest
      that EFs of initiation and set maintenance (examined by the semantic fluency
      task) may allow depressed elderly individuals to engage and stay in treatment.
      Identification of those at risk for noncompletion may help implementation
      strategies for personalized care. TRIAL REGISTRATION: ClinicalTrials.gov
      identifier: NCT00892047.

PMID- 29659206
TI  - Effects of Antipsychotics on Secular Mortality Trends in Patients With
      Alzheimer's Disease.
AB  - OBJECTIVE: To investigate secular changes in mortality rates between patients
      with Alzheimer's disease (AD) and the general population as well as changes in
      antipsychotic drug treatment and the association between drug treatment and
      mortality in patients with AD in Denmark during a 12-year study period. METHODS:
      This nationwide, retrospective cohort study identified all-cause mortality in all
      Danish patients with incident ICD-10-defined AD from 2000 through 2011. The
      cumulative antipsychotic dosages from dementia diagnosis until end of study for
      each participant were calculated and categorized in 1 of 5 groups per the World
      Health Organization Defined Daily Doses (DDDs). Data were obtained from relevant
      Danish national registers. RESULTS: The study included 32,001 patients (11,194
      male and 20,807 female). During the study period, an increasing trend was found
      in median survival time, but no decline was seen in standardized mortality
      ratios, which spanned from 1.19 (95% CI, 0.98-1.46) in 2001 to 1.52 (95% CI, 1.38
      1.68) in 2011. The findings showed a decline in proportion of patients with
      incident AD exposed to antipsychotic drugs as well as decline in mean annual
      cumulative DDDs. Adjusted Cox regression analyses revealed that current exposure
      to antipsychotic drugs was associated with increased mortality, although hazard
      ratios declined during the study period from 2.24 (95% CI, 2.07-2.43) in 2000
      2002 to 1.24 (95% CI, 1.09-1.41) in 2009-2011, with P values < .001. CONCLUSIONS:
      These findings appear to underscore the current guideline recommendations for
      using antipsychotic drugs at only the lowest effective dose and only in patients
      for whom all non-pharmacologic options have been exhausted. Furthermore, these
      results seem to indicate that the reduced use of antipsychotic drugs has no
      impact on relative mortality, suggesting that the AD population has gained less
      from improvements in care of other diseases that impact mortality rates in
      patients with AD as well as in the general population.

PMID- 29659207
TI  - Trajectories of Acute Antidepressant Efficacy: How Long to Wait for Response? A
      Systematic Review and Meta-Analysis of Long-Term, Placebo-Controlled Acute
      Treatment Trials.
AB  - BACKGROUND: In patients who are not responding to antidepressant pharmacotherapy,
      information regarding the future probability of response with the same treatment
      is scarce. Specifically, it is unclear at what point in time the probability to
      respond or remit ceases to increase, because few studies report data on response
      or remission at repeated time points beyond 4 or 8 weeks of treatment.
      Consequently, treatment recommendations in clinical practice guidelines differ
      widely. DATA SOURCES: We systematically searched MEDLINE, Embase, PsycINFO, and
      CENTRAL databases through March 2014 using generic terms for depressive or
      affective disorders, individual drug names, and placebo (Prospero Registration:
      CRD42014010105). STUDY SELECTION: We identified double-blind, randomized studies
      with continuous outcome reporting from 4 weeks up to at least 12 weeks that
      compared antidepressant monotherapy to placebo in adult patients suffering from
      acute depressive disorder. DATA EXTRACTION: Data extraction and synthesis
      followed Cochrane Collaboration guidelines. Primary outcome was response;
      secondary outcomes were remission and changes in rating scale scores in
      previously unresponsive patients, respectively. RESULTS: Of 6,043 articles
      screened, we selected 9 studies including 3,466 patients. Altogether, 21.6%
      (18.6%, 24.9%) of previously nonresponsive patients achieved response with
      ongoing antidepressant treatment between weeks 5 and 8, and 9.9% (7.5%, 12.7%),
      between weeks 9 and 12. Probability of response when taking placebo was 13.0%
      (9.9%, 16.5%) between weeks 5 and 8 and 2.4% (1.2%, 4.6%) between weeks 9 and 12.
      Differences in the probability of response between antidepressant and placebo
      translated into a number needed to treat of 11 after 4 weeks and 17 after 8
      weeks. Heterogeneity was low to moderate, and results remained stable across
      subgroup and sensitivity analyses. CONCLUSIONS: In patients unresponsive to
      antidepressant pharmacotherapy, improvements in psychopathology can be expected
      with ongoing antidepressant treatment for up to 3 months. After 8 weeks of
      treatment, improvement with ongoing monotherapy is relatively small.

PMID- 29659208
TI  - Posttraumatic Stress Disorder as a Significant Correlate of Voluntary
      Antiretroviral Treatment Interruption in Adult HIV-Infected Patients Followed up
      in French Hospitals: Data From the ANRS-VESPA2 National Survey.
AB  - OBJECTIVE: Although antiretroviral treatment (ART) no longer requires 100%
      adherence, voluntary treatment interruption (VTI) still may have a negative
      impact on virologic success. Previous studies have shown that posttraumatic
      stress disorder (PTSD) is more prevalent in HIV-infected patients than in the
      general population. However, no study has yet investigated the relationship
      between PTSD and VTI. We analyzed this relationship using data from a French
      national survey representative of HIV-infected adults followed up in hospitals.
      METHODS: A total of 3,022 HIV-infected adults participated in the ANRS-VESPA2
      survey (April 2011-January 2012) and answered a face-to-face questionnaire that
      included the Composite International Diagnostic Interview Short-Form to diagnose
      PTSD and assess sociobehavioral variables such as VTI. Multivariable logistic
      regression models were used to study the relationship between PTSD and VTI.
      RESULTS: Among the 2,768 ART-treated participants with available data for both
      PTSD screening and ART interruption (study sample), prevalence of PTSD was 13.3%,
      and 7.2% of individuals reported VTI during the previous month. After adjustment
      for being a female Sub-Saharan African immigrant and reporting harmful alcohol
      consumption (Alcohol Use Disorders Identification Test score >= 8), lifetime PTSD
      was found to be independently associated with VTI (adjusted odds ratio [95% CI] =
      1.64 [1.07-2.53], P = .025). CONCLUSIONS: PTSD is highly prevalent in HIV
      infected patients followed up in French hospitals and is a significant predictor
      of VTI. PTSD is a psychiatric disorder that is still underdiagnosed and
      undertreated in many countries despite its negative consequences on health
      behaviors. As there is evidence of effective treatment for PTSD, HIV care
      providers need to be trained in screening for this disorder.

PMID- 29659209
TI  - Improving the Diagnosis and Treatment of Pediatric Bipolar Disorder.
AB  - Reconsidering Insomnia as a Disorder Rather Than Just a Symptom in Psychiatric
      Practice Click to enlarge page Awareness of the prevalence and impact of bipolar
      disorder in pediatric patients has grown in recent years. Youths with this
      disorder are at risk for poor long-term outcomes, but with careful screening,
      clinicians may be able to detect early signs or subthreshold symptoms and provide
      a timely diagnosis and effective treatment. Although several pharmacologic
      options are available for patients aged 10 years and up, they differ in their
      safety and tolerability profiles. Clinicians should select the agent that best
      balances benefit and risk-at the lowest efficacious dose-and provide careful
      monitoring for adverse events throughout treatment. Johns Hopkins University and
      the Kennedy Krieger Institute, Baltimore, Maryland. (Dr Findling); Private
      practice, Menlo Park, California (Dr Chang) mask .

PMID- 29659210
TI  - Toward Understanding Sex Differences in the Prevalence of Posttraumatic Stress
      Disorder: Results From the National Epidemiologic Survey on Alcohol and Related
      Conditions.
AB  - BACKGROUND: It is unclear whether the higher prevalence of posttraumatic stress
      disorder (PTSD) in women than in men is due to sex differences in the prevalence
      of the exposure to traumatic events or to differences in vulnerability to
      traumatic events among those exposed to them. METHODS: We applied mediation and
      moderated mediation models to a large nationally representative sample of US
      adults (N = 34,653) drawn from Wave 2 (2004-2005) of the National Epidemiologic
      Survey on Alcohol and Related Conditions. RESULTS: A model that assumed that the
      effect of 19 traumatic events was the same across sexes and examined whether sex
      differences in the prevalence of DSM-IV PTSD were due exclusively to sex
      differences in exposure to traumatic events predicted similar prevalence of PTSD
      among men and women (indirect effect standardized beta = 0.04, P = .61), contrary
      to empirical findings. By contrast, a model that allowed the effect of 19
      traumatic events on risk of PTSD to vary by gender, while taking into account sex
      differences in the prevalence of exposure, indicated that, for 13 of the
      traumatic events, the effect was significantly greater in women than in men
      (range of standardized beta coefficients = 0.02-0.12, P < .05). The total
      indirect and direct effects of sex on PTSD in this model were, respectively, beta
      = 0.42 (P < .01) and beta = -0.03 (P = .76), indicating that all of the effect of
      sex on PTSD was explained by this moderated mediation model. CONCLUSIONS: The
      higher prevalence of PTSD among women appears to be due mainly to their greater
      vulnerability to the effects of traumatic events.

PMID- 29659211
TI  - Ketamine for Depression, 6: Effects on Suicidal Ideation and Possible Use as
      Crisis Intervention in Patients at Suicide Risk.
AB  - A growing body of literature suggests that ketamine, administered in
      subanesthetic doses, has early-onset antidepressant action in patients with
      severe and even treatment-refractory depression. Many case reports, open-label
      studies, and randomized controlled trials (RCTs) suggest that ketamine may have
      dramatic antisuicidal effects, as well. This article examines the benefits of
      ketamine in patients with suicidal ideation with particular focus on the findings
      of recent RCTs and meta-analyses. Important findings are that a single dose of
      ketamine is associated with antisuicidal benefits that emerge within an hour of
      administration and persist for up to a week. The benefits are seen in patients
      with mild as well as clinically significant suicidal ideation. The benefits are
      observed in midazolam- as well as saline-controlled trials. Effect sizes are
      medium to large. The improvement in suicidal ideation is only partly explained by
      improvement in depression severity. It is concluded that there is consistent
      evidence that a single dose of ketamine has dramatic antisuicidal action that
      emerges almost immediately after dosing and persists for at least a week. The
      short- and intermediate-term safety and efficacy of ketamine as a crisis
      intervention treatment for suicidal patients merit study. Areas that need
      research are outlined.

PMID- 29659212
TI  - Successful Use of Electroconvulsive Therapy in the Setting of Multiple Risk
      Factors for Retinal Detachment.

PMID- 29659213
TI  - Interfacial Property of Dental Cobalt-Chromium Alloys and Their Bonding Strength
      with Porcelains.
AB  - Porcelain-fused-to-metal crown is one of the widely-used prostheses among the
      dental porcelain restorations. Nonprecious metals like Ni-Cr and Co-Cr have
      extensively been used for metal-ceramic restorations due to advantages such as
      inexpensive price, hardness, durability, resistance to deformation, thin
      thickness of metal of porcelain area, and other mechanical and physical
      properties. However, the immediate advantage of the Co-Cr alloy is comparable
      performance to other base metal alloys, but without an allergenic nickel
      component. To achieve clinical longevity of porcelain-fused-to-metal (PFM)
      crowns, it is essential to have adequate bond strength between the metal
      substrate and porcelain. Any type of metal-ceramic fracture failure can become a
      costly and timeconsuming problem, both in the clinic and laboratory. Therefore,
      the suitability of the Co-Cr alloy for dental applications is critically
      associated with its ceramic bonding capacity. In this study, Co-Cr metal alloys
      modified by acid-etching and sandblasting, oxide layer was formed for subsequent
      bonding to porcelain ceramics. By both acid-etching and sandblasting oxide layer
      was formed and showed higher bonding strength at a proper condition, but
      debonding was occurred at porcelain layer so that they showed highest bonding
      strength by combined these two kind of surface treatment. Because the oxide film
      was formed more densely in a vacuum at the portions where more sophisticated
      concavo-convex were formed on the surface of a metal.

PMID- 29659214
TI  - Investigations of Magnetic Properties of Oleic Acid and Oleyl Amine Capped
      Nanostructured Co( x) Ni(1-x)  (0.2 <= x <= 0.8) Alloys.
AB  - In this study, nanocrystalline oleic acid and oleyl amine capped Co x Ni1-x 
      alloys (x = 0.2, 0.4, 0.6, 0.8) have been synthesized via chemical reduction
      route. As-prepared as well as annealed samples were characterized using FTIR
      spectroscopy, X-ray diffraction and transmission electron microscopy. CoNi alloys
      were found to be capped with oleic acid-oleylamine complex even after heat
      treatment up to 400  degrees BC. XRD patterns confirm that the CoNi alloys
      crystallize in pure fcc phase with average crystallite sizes in the range of 8-11
      nm. TEM micrographs confirm nearly spherical morphologies with narrow particle
      size distribution of the synthesized CoNi alloys. Average TEM particle sizes
      range from 7 nm to 12 nm. As-prepared as well as annealed CoNi alloys are
      ferromagnetic in nature at 298 K. M s values for annealed CoNi alloys are found
      to be in the range of 25-59.6 emu/g after correction for weight fraction of
      capped matrix and H c values are in the range of 52-314 Oe. Observed magnetic
      properties have been interpreted on the basis of size effects, altered crystal
      anisotropies and spin canting on the surface. FC/ZFC magnetization measurements
      show magnetic irreversibility and superparamagnetic blocking of nanoparticles due
      to strong dipolar interactions and particle size distribution. A structure
      property correlation in CoNi alloys has been attempted in this investigation.

PMID- 29659215
TI  - The effect of recasting on biological properties of Ni-Cr dental alloy.
AB  - Introduction: Increases in market prices of gold over the last 20 years have led
      to expansion of basicdental alloys, which, primarily due to their good mechanical
      properties and acceptable prices, havefound their place in everyday dental
      practice. However, within the procedure of making dental prostheticrestorations,
      the alloys are melted and cast, which leads to changes in their physical,
      mechanical andbiological properties. Objective: The objective of the study was to
      test biocompatibility of a Ni-Cr dental alloy (WIRON99) depending on the number
      of melting and casting processes. Methods: The working method included the
      testing of cytotoxicity of the alloy obtained by castingafter one, after four,
      and after eight successive processes of melting. Cytotoxicity of samples
      wastested by means of a 24-hour and a three-day cytotoxicity test, done on L929
      fibroblasts. Results: A repeatedly melted and cast alloy shows a reduced
      biocompatibility and causes specificresponses of the tissues in the surrounding
      area. Since the cytotoxic effect is more significant inthe extended contact with
      the culture cells, a three-day cytotoxicity test showed discrete changeswhich
      were the indicator of cell growth inhibition in the cell culture. Conclusion: The
      obtained results confirm the working hypothesis that repeated alloy melting
      andcasting will decrease biocompatibility of dental alloys and will lead to
      specific responses of thetissue in the surrounding area.

PMID- 29659216
TI  - Self-perception and satisfaction with dental appearance and aesthetics with
      respect to patients' age, gender, and level of education.
AB  - Introduction: Patient's subjective evaluation of dental appearance and aesthetics
      is becoming an increasinglyimportant factor in aesthetic treatments and
      prosthetic therapy. Objective: The aim of this study was to investigate the
      influence of age, education level, gender, anddifferent dental status and the
      appearance of the upper anterior teeth (color, size, shape, position andalignment
      of the anterior teeth) on the satisfaction of the respondents with dental
      appearance andaesthetics of their upper anterior teeth and their desire for
      improvement. Methods: The study encompassed 480 people aged 20 to 50 years with
      an average age of 30.84 years.There were 236 male and 244 female subjects. The
      respondents were interviewed using a questionnairespecially designed for the
      purpose of this research. For the study, the subjects were divided into
      thefollowing three age groups: the younger age group (20-30 years of age), the
      middle age group (31-40years of age), and the older age group (41-50 years of
      age). Results: The conducted study did not reveal statistical significance with
      respect to gender in any of theexamined parameters (p > 0.05). A little more than
      one half of the respondents in each age group weresatisfied with their dental
      appearance and aesthetics (60.3% of the respondents in the age group of 20
      30years, 55.7% in the age group of 31-40, and 53.7% in the age group of 41-50
      years of age). Satisfactionwith dental appearance and aesthetics increases
      linearly with the increase in the level of education andwas the highest among the
      respondents with university degree (33.3%). Conclusion: Female respondents were
      more dissatisfied with their dental appearance and aestheticsas compared with
      male respondents, but the difference was found to be non-significant. Patients
      withhigher education level were more satisfied with their dental appearance and
      aesthetics than those withlower education.

PMID- 29659217
TI  - The effects of implementation of guideline-directed medical therapy on relief of
      angina in patients with stable coronary artery disease in Serbia.

PMID- 29659218
TI  - Is pacemaker therapy the right key to patients with vasovagal syncope?
AB  - Introduction: Vasovagal syncope is the most common type of reflex syncope.
      Efficacy of cardiac pacingin this indication has not been the subject of many
      studies and pacemaker therapy in patients withvasovagal syncope is still
      controversial. Objective: This study aimed to assess the efficacy and safety of
      pacing therapy in treatment of patientswith vasovagal syncope, to determine
      contribution of new therapeutic models in increasing its success,and to identify
      risk factors associated with a higher rate of symptoms after pacemaker
      implantation. Methods: A retrospective study included 30 patients with pacemaker
      implanted due to vasovagal syncopein the Pacemaker Center, Clinical Center of
      Serbia, between November 2003 and June 2014. Head-uptilt test was performed to
      diagnose vasovagal syncope. Patients with cardioinhibitory and mixed typeof
      disease were enrolled in the study. Results: Mean age was 48.1 +/- 11.1 years and
      18 (60%) patients were men. Mean follow-up period was5.9 +/- 3.0 years.
      Primarily, implantable loop recorder was implanted in 10 (33.3%) patients. Twenty
      (66.7%)patients presented cardioinhibitory and 10 (33.3%) mixed type of vasovagal
      syncope. After pacemakerimplantation, 11 (36.7%) patients had syncope. In
      multiple logistic regression analysis we showed thatsyncope is statistically more
      likely to occur after pacemaker implantation in patients with mixed type
      ofvasovagal syncope (p = 0.018). There were two (6.7%) perioperative surgical
      complications. Conclusion: Pacemaker therapy is a safe treatment for patients
      with vasovagal syncope, whose efficacycan be improved by strict selection of
      patients. We showed that symptoms occur statistically more oftenin patients with
      mixed type of disease after pacemaker implantation.

PMID- 29659219
TI  - The role of the color Doppler ultrasonography and computed tomography in
      estimation of portal hypertension.
AB  - Introduction: Liver diseases with disturbances of hepatic and splanchnic
      circulation lead to the portal hypertension, with or without a portal vein
      thrombosis. Objective: This study was based on the testing of hypothesis that
      more data and more precise diagnosisin patients with disorders of portal
      circulation can be obtained by using color Doppler ultrasonography(CDU) and
      computed tomography (CT) with contrast. Methods: The study was conducted from
      February 2011 to May 2014 and it comprised 120 patientswho were suspected to have
      portal hypertension or already had clinical confirmation of the portal
      hypertension,patients with hepatitis, and some patients with hematological
      diseases. The first group of40 patients was examined by conventional
      ultrasonography and CDU, the second group by contrast CT,and the third group of
      patients was examined by both methods (CDU and contrast CT). After six monthsof
      adequate therapy, the patients had control examinations with the same diagnostic
      technique usedduring their first examination. Results: Retrospective analysis
      showed that CDU is more sensitive than CT in the assessment of presenceand age of
      thrombi (CDU 93.9%; CT 86.1%). CT gives precise data in detection of
      portosystemiccollaterals. Sensitivity of CT is 100% and its specificity is 67%.
      Cumulative sensitivity and specificity formost parameters were increased in
      patients with portal hypertension when both methods were applied. Conclusion:
      This study emphasizes the possibility of early and more accurate diagnosis
      achieved whencombining two radiological techniques (CDU and contrast CT scan),
      which is not the case when thesemethods are used separately.

PMID- 29659220
TI  - Nanosized Hydroxyapatite Precipitation on the Ti-30Ta-xHf Alloys.
AB  - In this study, we prepared hydroxyapatite (HAp) layer on the alkali treated Ti
      30Ta-xHf alloys using electrochemical deposition method. Ti-30Ta-xHf alloys was
      anodized in 5 M NaOH solution at 0.3 A for 10 min. Alkali treated Ti-30Ta-xHf
      surface formed by anodization step which acted as templates and anchorage for
      growth of the HAp during subsequent pulsed electrochemical deposition process at
      85  degrees C. The phase and morphologies of deposited HAp layer were affected by
      the Hf contents of Ti-30Ta-xHf alloys. The nano-scale rod-like HAp layer was
      formed on untreated Ti-30Ta-xHf alloys with partially low crystallinity. In the
      case of alkali treated Ti-30Ta-xHf, nano-sized needle-like layers were
      transferred to nano-flake surface and denser morphology as Hf content increased.

PMID- 29659221
TI  - Prevalence and risk factors of vascular calcification in pre-dialysis patients
      with Balkan endemic nephropathy.
AB  - Introduction: Vascular calcifications (VC) are common in patients with chronic
      kidney disease and presentone of manifestations of mineral and bone disorders in
      these patients. Objective: The aim of this pilot study was to examine the
      prevalence and risk factors of VC in pre-dialysispatients with Balkan endemic
      nephropathy (BEN) and other kidney diseases. Methods: The study involved 32 pre
      dialysis patients, 15 with BEN and 17 with other kidney diseases. Allthe patients
      underwent an interview, objective examination, routine laboratory analyses and
      measurementof serum concentration of intact parathyroid hormone (iPTH), 25
      hydroxyvitamin D3 [25(OH)D3]and osteopontin. VCs in iliac, femoral, radial, and
      digital arteries were evaluated and Adragao VC scorewas calculated. The samples
      of radial artery were collected during the first creation of an
      arteriovenousfistula, and expression of osteocalcin, bone morphogenic protein-2
      osteopontin, and matrix Gla-proteinin arterial wall were examined. Results:
      Patients with BEN were significantly older (71.1 +/- 6.1 vs. 54.7 +/- 11.1
      years), but they had significantlylower systolic and mean blood pressure (95.7 +/
      13.2 mmHg vs. 104.3 +/- 7.4 mmHg) and lower serumconcentration of phosphorus
      (1.32 +/- 0.36 mmol/l vs. 1.65 +/- 0.35 mmol/l) and cholesterol (4.3 +/- 1.1
      mmol/lvs. 5.2 +/- 0.8 mmol/l) than patients with other kidney diseases. Mean VC
      score was significantly lowerin patients with BEN than in those with other kidney
      diseases (2.8 +/- 1.7 vs. 4.6 +/- 1.8; p = 0.009), butexpression of four examined
      proteins in arterial wall differed insignificantly between the two groups.VC
      score correlated significantly with serum concentrations of cholesterol,
      triglycerides (positively), andiPTH (negatively). Conclusion: Pre-dialysis BEN
      patients had a significantly lower mean score of VC than patients with
      otherkidney diseases.

PMID- 29659222
TI  - Biochemical liver function test parameter levels in relation to treatment
      response in liver metastatic colorectal patients treated with FOLFOX4 with or
      without bevacizumab.
AB  - Introduction: Combined use of bevacizumab and conventional anticancer drugs leads
      to a significantimprovement of treatment response in patients with metastatic
      colorectal carcinoma (CRC). Conventionaltreatment protocols exert undesired
      effects on the liver tissue. Hepatotoxic effects are manifested as adisturbance
      of liver function test parameters. The relation between clinical outcome and
      disorder ofbiochemical parameters has not been completely evaluated. Objective:
      The objective of our study was to examine whether clinical outcome in patients
      with livermetastatic CRC correlates with the level of liver function test
      parameters. Methods: The study included 96 patients with untreated liver
      metastatic CRC who received FOLFOX4protocol with or without bevacizumab.
      Biochemical liver parameters were performed before and afterthe treatment
      completion. Treatment response was evaluated as disease regression, stable
      disease, anddisease progression. The patients were divided into three groups
      according to the accomplished treatmentresponse. Results: In the group of
      patients with disease regression the post-treatment levels of aspartate
      aminotransferase,alanine aminotransferase, and bilirubin were statistically
      significantly increased. In contrastto this, gamma-glutamyltransferase and
      protein post-treatment values were significantly lower in relationto initial
      values. In patients with stable disease, difference was found only in the level
      of proteins beinglower after the treatment. In patients with disease progression,
      values of aspartate aminotransferase andbilirubin were significantly increased
      after completed treatment. Conclusion: Treatment responses are not completely
      associated with the level of liver function test parameters.The only parameter
      which correlated with treatment response is gamma-glutamyltransferase.Its
      decrease is accompanied with disease regression.

PMID- 29659223
TI  - Bismuth Oxychloride Nanoplates Prepared by a Single-Source Organometallic
      Reactant Bismuth Hexafluoroacetylacetonate and Their Excellent Photocatalytic
      Performance.
AB  - Bismuth oxychloride (BiOCl) is well known for its photocatalytic activity and
      many methods are reported to prepare this layered-structure material. In this
      study, bismuth hexafluoroacetylacetonate Bi(C5HF6O2)3 was chosen as Bi source in
      the synthesis of BiOCl. Uniform BiOCl nanoplates were fabricated without any
      organic additive to control the morphology. In the formation process,
      Bi(C5HF6O2)3 acted as both reagent and soft-template agent. Moreover BiOCl
      nanoplates exhibited quite high photocatalytic activity. Both P25 and BiOCl
      nanoplates can decompose the whole RhB dye within 30 minutes, which indicates
      that BiOCl nanoplates are of the comparative photocatalytic performance as P25.

PMID- 29659224
TI  - Negative-pressure wound therapy for deep groin vascular infections.
AB  - Introduction: Infection of synthetic graft in the groin is a rare but devastating
      complication. When itoccurs, several possibilities of treatment are available.
      Extra-anatomic reconstruction and in-situ implantationof new, infection resistant
      grafts are associated with high mortality and morbidity. Therefore,more
      conservative approach is needed in some cases. Negative-pressure wound therapy is
      one of theoptions in treating such patients. Objective: The aim of this study was
      to assess the outcome for deep groin vascular graft infection treatedwith
      negative-pressure wound therapy. Methods: Seventeen patients (19 wounds), treated
      for Szilagyi grade III groin infections between October2011 and June 2014, were
      enrolled into this observational study. Results: Majority of the wounds (11/19)
      were healed by secondary intention, and the rest of the wounds(8/19) were healed
      by primary intention after initial negative-pressure wound therapy and graft
      substitutionwith silver-coated prostheses or autologous artery/vein implantation.
      No early mortality wasobserved. Minor bleeding was observed in one patient.
      Reinfection was noted in three wounds. Onlyone graft occlusion was noted. Late
      mortality was observed in three patients. Conclusion: Negative-pressure wound
      therapy seems to be safe for groin vascular graft infections andcomfortable for
      both patient and surgeon. However, the rate of persistent infection is high. This
      technique,in our opinion, can be used as a "bridge" from initial wound
      debridement to definitive woundmanagement, when good local conditions are
      achieved for graft substitution, either with new syntheticgraft with
      antimicrobial properties or autologous artery/vein. In selected cases of deep
      groin infectionsit can be used as the only therapeutic approach in wound
      treatment.

PMID- 29659225
TI  - Risk factors for severe influenza A virus infections in post-2009 pandemic
      period.
AB  - Introduction: Literature data concerning risk factors for severe influenza in
      post-2009 pandemic period,from low- and middle-income Central and Eastern
      European countries are very limited. Objective: The aim of this study was to
      investigate the risk factors for severe A(H1N1)pdm09 and A(H3N2)influenza during
      the post-2009 pandemic period. Methods: During four consecutive seasons of
      2010/2011-2013/2014, nasopharyngeal or nasal and pharyngealswab samples from 153
      patients with mild and 147 patients with severe influenza were testedusing real
      time reverse transcription polymerase chain reaction (real-time RT PCR) assays.
      Results: The study indicated three statistically significant risk factors of
      influenza severity, including presenceof chronic underlying illness/condition
      [odds ratio (OR) of 15.2, 95% confidence interval (CI) of1.8-125.4, p = 0.001),
      age >=15 years (OR 9.2, 95% CI 3.5-24.1, p < 0.001), and delay in medical care
      ofmore than two days after the symptoms onset (OR 3.2, 95% CI 1.6-6.4, p =
      0.001). Conclusion: Obtained results confirmed that patients with chronic
      underlying illness/condition andolder than 15 years had the highest risk for
      serious complications from influenza and highlighted theimportance of start of
      antiviral therapy within the first two days of illness in order to reduce the
      risk forthe most severe outcomes of influenza, such as acute respiratory distress
      syndrome and lethal outcome.

PMID- 29659228
TI  - Quality of osteoarthritis care in family medicine - A cross-sectional study.
AB  - Introduction: Effective treatments for osteoarthritis are available, yet little
      is known about the quality ofprimary care in the Republic of Srpska for this
      disabling condition. Objective: The main objective of this study was to analyze
      the overall quality of osteoarthritis treatmentin a family medicine setting, as
      well as to explore whether the achievement of quality indicators wasassociated
      with particular patient characteristics and severity of osteoarthritis. Methods:
      The cross-sectional study included 120 patients with confirmed hand, knee, and
      hip osteoarthritis,recruited at seven family practices in the town of Ugljevik,
      Republic of Srpska, Bosnia and Herzegovina.Data were extracted from a patient
      questionnaire on quality indicators, as well as from their electronicand paper
      records, to assess care against 14 indicators. The included quality indicators
      were based onthe Arthritis Foundation's Quality Indicator set for Osteoarthritis.
      Summary achievement rates for hip,knee, or hand osteoarthritis, as well as for
      the total sample, were calculated. Results: The mean achievement rate for all 14
      quality indicators obtained from medical records was74%, and 77% obtained from
      patient interview. The quality indicators concerning referral for weightreduction
      (23%) and pharmacological treatment (24%) had the lowest achievement rates,
      whereas thehighest achievement rates were related to physical examination (100%),
      pain and functional assessment(100%), and education (90.8%). Patients physical
      functioning was significantly associated with the qualityindicator achievement
      rate (p = 0.001). Conclusion: Pharmacological therapy and the referral of
      osteoarthritis patients in need of weight reductionseem to have the greatest
      potential for improvement in primary health care.

PMID- 29659229
TI  - The onset of systemic lupus erythematosus and thyroid dysfunction following
      Graves' disease - A case report and literature review.
AB  - Introduction: Graves' disease is a multifactorial autoimmune thyroid disease,
      with the presence of typicalcirculating autoantibodies that can activate the
      thyroid hormone receptors, resulting in hyperthyroidism,goiter, and
      ophthalmopathy. Systemic lupus erythematosus is a multi-systemic autoimmune
      diseasethat involves almost all the organs of the human body and is characterized
      by autoantibodies formation.Several studies have reported that autoimmune thyroid
      and rheumatic disorders can present anunusual relationship. Case Outline: We
      report a case of a middle-aged woman who presented with systemic lupus
      erythematosusone year after being diagnosed with Graves' disease. Prednisone and
      cyclophosphamide wereadministered to control the development of systemic lupus
      erythematosus. Furthermore, a percutaneousthyroid biopsy was performed for
      further confirmation of Graves' disease. Methimazole instead ofpropylthiouracil
      was added into the therapeutic scheme. A month later, the patient's clinical
      manifestationand laboratory tests got significant improvement, except that new
      thyr o id dysfunction appearedopposite to the original one. The administration of
      anti-thyroid drug was discontinued. With a periodof decreased administration of
      prednisone, the patient's thyroid function gradually got back to normallevels
      without any levothyroxine replacement. Conclusion: In conclusion, the clinical
      use of prednisone and antithyroid drugs may result in instabilityof the
      hypothalamus-pituitary-thyroid axis, and thyroid function should be carefully
      monitored in suchpatients.

PMID- 29659230
TI  - The Effect of Temperature on Photoluminescence Enhancement of Quantum Dots in
      Brain Slices.
AB  - In this paper, we investigated the effect of temperature on photoluminescence of
      quantum dots immobilized on the surface of an optical fiber in a rat brain slice.
      The optical fiber was silanized with 3-aminopropyl trimethoxysilane (APTMS),
      following which quantum dots with carboxyl functional group were immobilized on
      the optical fiber via amide bond formation. The effect of temperature on the
      fluorescence intensity of the quantum dots in rat brain slices was studied. This
      report shows that the fluorescence intensity of quantum dots increases with the
      increase of temperature of the brain slice. The fluorescence enhancement
      phenomenon appears to take place via electron transfer related to pH increase.
      With the gradual increase of temperature, the fluorescence intensity of quantum
      dots in solution decreased, while that in the brain slice increased. This
      enhanced thermal performance of QDs in brain slice makes suggestion for the study
      of QDs-based brain temperature sensors.

PMID- 29659231
TI  - Synchronous advanced pulmonary tuberculosis and acute virus myocarditis mimicked
      Wegener granulomatosis in a 26-year-old man - A case report.
AB  - Introduction: Tuberculosis patients are rarely asymptomatic. Acute virus
      myocarditis presents with a widerange of symptoms, from mild dyspnea or chest
      pain to cardiogenic shock and death. Case Outline: A 26-year-old Caucasian man
      non-smoker presented with one-week history of lower extremities'swelling. The
      patient's medical history also revealed a two-day episode of subfebrile
      temperaturewith scanty hemoptysis three weeks prior to admission. The episode had
      not provoked him toseek medical care. Physical examination revealed generalized
      oedema, and laboratory analysis showedsigns of acute renal insufficiency.
      Enlarged heart and hilar shadows, bilateral massive cavitary pulmonaryopacities
      and pleural effusion were found at chest radiography. Sputum smears were
      Mycobacterianegative on direct microscopy. Electrocardiogram changes and
      echocardiography were suggestive ofacute myocarditis with dilated cardiomyopathy.
      IgM titer to adenovirus was positive. Under diuretics,angiotensin-converting
      enzyme inhibitor, beta-blocker, antibiotics and bed rest, fast heart
      compensationand renal function repair were achieved. Radiographic pulmonary
      changes promptly regressed exceptfor a cavity in the right upper lobe. Bronchial
      aspirate from the affected lobe was Mycobacteria positiveon direct microscopy and
      culture positive for Mycobacterium tuberculosis. Standard anti-tuberculosisdrug
      regimen led to recovery. Conclusion: In the unusual common existence of two
      diseases whose presentation initially mimickedWegener's granulomatosis, acute
      dilated cardiomyopathy contributed to pulmonary tuberculosis detection.To prevent
      diagnostic delay in tuberculosis, further efforts in population education are
      necessarytogether with continual medical education

PMID- 29659232
TI  - Atypical, polyarticular lipoma arborescens in a child.
AB  - Introduction: Lipoma arborescens is a rare, tumor-like lesion commonly involving
      synovial joints andless commonly bursae and synovial tendon sheaths. Case
      Outline: We report a case of a 12-year-old boy with symmetric involvement of the
      bicipitoradialbursae, synovial sheaths of extensor compartments of both hands and
      medial ankles. The diagnosis ofpolyarticular lipoma arborescens was proposed on
      magnetic resonance (MR) imaging and this diagnosiswas histologically proven after
      biopsy of the bursae and later by open surgery of the synovial sheath ofthe right
      ankle tendons. Literature search was performed and twelve cases with
      polyarticular involvementwere analyzed. Lipoma arborescens commonly involves
      suprapatellar recess of the knee and very rarelyother joints or bursae.
      Histological analysis revealed an accompanying non-necrotizing
      granulomatoussynovial inflammation. Conclusion: Polyarticular lipoma arborescens
      is a rare entity and symmetrical involvement of the jointsother than the knees is
      exceedingly rare. MR imaging plays a significant role in the diagnostic
      protocol,and the characteristic fatty signal on MR imaging is highly suggestive
      of lipoma arborescens.

PMID- 29659233
TI  - Fondaparinux monitoring in a patient with heparin-induced thrombocytopenia on
      hemodialysis.
AB  - Introduction: Heparin-induced thrombocytopenia associated to hemodialysis is
      rare. In case when citratedialysis and/or non-heparin anticoagulants are not
      available, only possible medication to use foranticoagulation during hemodialysis
      is fondaparinux. However, laboratory monitoring of fondaparinuxbased on anti-Xa
      activity in dialysis patients has not been sufficiently documented yet. Case
      Outline: We created a local anti-factor Xa assay for measuring fondaparinux
      plasma concentrationand efficacy in a patient with heparin-induced
      thrombocytopenia during hemodialysis. Fondaparinuxgiven subcutaneously increases
      risk of adverse events due to its extended release and prolonged maintenanceof
      toxic levels. When used intravenously fondaparinux remains safe, with reached
      steady-statelevel within dialysis and low risk of toxicity afterwards.
      Conclusion: Fondaparinux may be used as an alternative anticoagulant medication
      during hemodialysisin patients who develop heparin-induced thrombocytopenia.
      Adequate dose must be adjusted topatients' dry weight (0.03 mg/kg intravenously)
      and fondaparinux anti-coagulation monitoring mustbe provided.

PMID- 29659235
TI  - Hepatocellular carcinoma and impact of aflatoxin difuranocoumarin derivative
      system - A case report.
AB  - Introduction: Hepatocellular carcinoma (HCC) is the most frequent type of liver
      malignancy. As a carcinogen,aflatoxin B1 (AFB1) causes HCC by inducing
      deoxyribonucleic acid adducts that lead to geneticchanges in liver cells and may
      be the cause of HCC in up to 30% of cases. The incidence of HCC has beenon the
      rise and is an issue in the countries of the Western Balkans. Case Outline: This
      paper presents a case of a 37-year-old woman who was diagnosed with HCC,
      withouthepatitis B, hepatitis C, or liver cirrhosis. The patient consumed milk
      and dairy products in quantities ofover two liters per day over the course of 20
      years, which indicates the impact of aflatoxin in milk onHCC. A positive signal
      for the presence of AFB1 was detected by ELISA (enzyme-linked immunosorbentassay)
      in-house using immunoperoxidase screening test. Conclusion: As carcinogenic
      difuranocoumarin derivative, aflatoxin B1 is the most likely cause of
      malignanttransformation of hepatocytes, which resulted in hepatocellular
      carcinoma in this patient.

PMID- 29659234
TI  - Mucormycosis of the paranasal sinuses in a patient with acute myeloid leukemia.
AB  - Introduction: Invasive fungal infection is among the leading causes of morbidity,
      mortality, and economicburden for patients with acute leukemia after induction of
      chemotherapy. In the past few decades, theincidence of invasive fungal infection
      has increased dramatically. Its management has been furthercomplicated by the
      increasing frequency of infection by non-Aspergillus molds (e.g. Mucorales).
      Neutropenicpatients are at a high risk of developing an invasive mucormycosis
      with fulminant course andhigh mortality rate (35-100%). Case Outline: We are
      presenting the case of a 72-year-old male with an acute monoblastic leukemia.The
      patient was treated during five days with hydroxycarbamide 2 * 500 mg/day,
      followed by cytarabine2 * 20 mg/sc over the next 10 days. He developed febrile
      neutropenia, headache, and edema ofthe right orbital region of the face. Computed
      tomography of the sinuses revealed shadow in sinuseswith thickening of mucosa of
      the right paranasal sinuses. Lavage and aspirate from the sinuses
      revealedRhizopus oryzae. Mucormycosis was successfully treated with amphotericin
      B (5 mg/kg/day) followed byketoconazole (400 mg/day). Two months later the
      patient died from primary disease. Conclusion: In patients with acute leukemia
      who developed aplasia, febrile neutropenia, and pain inparanasal sinuses, fungal
      infection should be taken into consideration. New and non-invasive methods
      fortaking samples from sinuses should be standardized in order to establish an
      early and accurate diagnosisof mucormycosis with the source in paranasal sinuses,
      and to start early treatment by a proper antifungaldrug. Clear communication
      between physician and mycologist is critical to ensure proper and timelysampling
      of lavage and aspirate from sinuses and correct specimen processing when
      mucormycosis issuspected clinically.

PMID- 29659236
TI  - Shiga toxin-producing Escherichia coli hemolytic uremic syndrome.
AB  - The hemolytic-uremic syndrome (HUS) is characterized by microangiopathic
      hemolytic anemia, thrombocytopenia,and acute kidney injury (AKI). The major cause
      of HUS in childhood (>90%) is infection withverocytotoxin (Shiga-like toxin -
      "Stx")-producing bacteria, usually enterohemorrhagic Escherichia coli(VTEC/STEC).
      The infection may be transmitted by the consumption of undercooked meat,
      pasteurizeddairy products, contaminated vegetables, fruits and water, or by
      contact with STEC diarrhea. After anincubation period of three to eight days,
      patients commonly develop bloody diarrhea followed in 5-22%by HUS that may be
      complicated by central nervous system, pancreatic, skeletal, and myocardial
      involvement.HUS is one of the main causes of AKI in children in Europe. The
      management of HUS includes theusual treatment of children with AKI. Transfusion
      with packed red blood cells is needed in case of a severeanemia, while platelet
      transfusions are limited to the need for a surgical procedure or in active
      bleeding.Currently, there is no consensus on the use of antibiotic therapy.
      Treatment with plasma and/or plasmaexchange has not been proven beneficial in
      STEC-HUS. Eculizumab has been used for the treatment ofSTEC-HUS, but the value of
      this treatment remains to be determined. The mortality of HUS is reportedto be 3
      5%. About 12% of patients will progress to end-stage renal failure within four
      years and about25% will have long-term complications, including hypertension,
      proteinuria, renal insufficiency, andinsulin-dependent diabetes mellitus.
      Transplantation can be performed without increased risk for therecurrence of the
      disease.

PMID- 29659237
TI  - Development of cardiopulmonary bypass - A historical review.
AB  - The idea of isolated organ perfusion, a precursor of cardiopulmonary bypass, came
      by Legalois in 1812.First isolated organ perfusion was described by Loebell in
      1849. The first closed system for oxygenationand returning the blood through
      arteries was created by Frey and Gruber in 1885. Gibbon Jr. is consideredthe
      father of extracorporeal circulation. In spring of 1934 he began constructing a
      machine for extracorporealcirculation in Boston. He published the first
      description of this system in 1937. Gibbon won thegrant of the International
      Business Machines Corporation for developing the machine in 1947. Togetherthey
      developed Model I in 1949 and Model II in 1951. After a few unsuccessful attempts
      in 1952, thefirst successful surgical intervention on the heart (closure of
      atrial septal defect) using cardiopulmonarybypass was performed on May 6, 1953.
      In 1945, Kirklin and his working group reported on a series ofeight successfully
      treated patients in a row who underwent surgery with extracorporeal circulation.
      Firstsuccessful valve surgery under the direct vision was performed by Dodrill in
      1952, using his "MichiganHeart" machine as a right heart bypass. Using
      cardiopulmonary bypass, cardiac surgeons can deal withthe complex cardiac
      pathology and save millions of lives.

PMID- 29659238
TI  - Postponed diagnosis of alpha-1 antitrypsin deficiency.

PMID- 29659239
TI  - Adverse Reproductive Health Outcomes and Exposure to Gaseous and Particulate
      Matter Air Pollution in Pregnant Women.
AB  - Introduction: There is growing epidemiologic evidence of associationsbetween
      maternal exposure to ambient airpollution and adverse birth outcomes, such
      aspreterm birth (PTB). Recently, a few studies havealso reported that exposure to
      ambient air pollutionmay also increase the risk of some commonpregnancy
      complications, such as preeclampsiaand gestational diabetes mellitus (GDM).
      Researchfindings, however, have been mixed. These inconsistentresults could
      reflect genuine differences inthe study populations, the study locations, the
      specificpollutants considered, the designs of the study,its methods of analysis,
      or random variation.Dr. Jun Wu of the University of California-Irvine, a
      recipient of HEI's Walter A. RosenblithNew Investigator Award, and colleagues
      haveexamined the association between air pollutionand adverse birth and pregnancy
      outcomes inCalifornia women. In addition, they examined theeffect modification by
      socioeconomic status (SES)and other factors. Approach: A retrospective nested
      case-control study wasconducted using birth certificate data from about4.4
      million birth records in California from 2001 to2008. Wu and colleagues analyzed
      data on lowbirth weight (LBW) at term (infants born between37 and 43 weeks of
      gestation and weighing lessthan 2500 g), PTB (infants born before 37 weeks
      ofgestation), and preeclampsia (including eclampsia)of the mother during the
      pregnancy. In addition,they obtained data on GDM for the years 2006-2008. In the
      analyses, all outcomes were includedas binary variables.Maternal residential
      addresses at the time ofdelivery were geocoded, and a large suite of airpollution
      exposure metrics was considered, suchas (1) regulatory monitoring data on
      concentrationsof criteria pollutants NO2, PM2.5 (particulatematter <= 2.5 MUm in
      aerodynamic diameter), andozone (O3) estimated by empirical Bayesian kriging;(2)
      concentrations of primary and secondaryPM2.5 and PM0.1 components and sources
      estimatedby the University of California-DavisChemical Transport Model; (3)
      traffic-related ultrafineparticles and concentrations of carbonmonoxide (CO) and
      nitrogen oxides (NOx) estimatedby a modified CALINE4 air pollution
      dispersionmodel; and (4) proximity to busy roads, roadlength, and traffic density
      calculated for differentbuffer sizes using geographic information systemtools. In
      total, 50 different exposure metrics wereavailable for the analyses. The exposure
      of primaryinterest was the mean of the entire pregnancyperiod for each mother.For
      the health analyses, controls were randomlyselected from the source population.
      PTB controlswere matched on conception year. Term LBW, preeclampsia,and GDM were
      analyzed using generalizedadditive mixed models with inclusion of arandom effect
      per hospital. PTB analyses were conductedusing conditional logistic regression,
      withno adjustment for hospital. The main results-adjusted for race and education
      as categorical variablesand adjusted for maternal age and medianhousehold income
      at the census-block level-werederived from single-pollutant models. Main results
      and interpretation: In its independent review of the study, the HEIHealth Review
      Committee concluded that Wu andcolleagues had conducted a comprehensive
      nestedcase-control study of air pollution and adversebirth and pregnancy
      outcomes. The very large dataset and the extensive exposure assessment
      werestrengths of the study.The study documented associations betweenincreases in
      various air pollution metrics andincreased risks of PTB, whereas the evidence
      wasweaker overall for term LBW; in addition, decreasesin many air pollution
      metrics were associated withan increased risk of preeclampsia and GDM,
      anunexpected result.The investigators suggested that underreportingin the
      registry data, especially in lower-SESgroups, might have caused the many negative
      associationsfound for preeclampsia and GDM. In addition,poor geocoding was listed
      as a potentialexplanation, affecting in particular the results thatwere based on
      measures of proximity to busy roadsand traffic density in the smallest buffer
      size (50m). However, those issues were not fully explored.In general, the
      Committee thought that the analysisof road traffic indicators in the 50 m buffer
      washampered by the lack of contrast and that theresults are therefore difficult
      to interpret.Some other issues with the analytical approachesshould be considered
      when interpreting the results.Only a subset of controls was used, to reduce
      computationaldemands. Hence, some models did notconverge, especially in the
      subgroup analyses.Most of the results in the report were based onanalyses using
      single-pollutant models, which is areasonable approach but ignores that people
      areexposed to complex mixtures of pollutants. TheCommittee believed that the few
      two-pollutantmodels that were run provided important insights:these models showed
      the strongest association forPM2.5 mass, whereas components and source
      specificpositive associations largely disappearedafter adjusting for PM2.5 mass.
      This study adds tothe ongoing debate about whether some particlecomponents and
      sources are of greater publichealth concern than others.

PMID- 29659240
TI  - Ambient Air Pollution and Adverse Pregnancy Outcomes in Wuhan, China.
AB  - Background: Several recent studies have suggested that maternalexposures to air
      pollution and temperature extremesmight contribute to low birth weight
      (LBW),preterm birth (PTB), and other outcomes that can adverselyaffect infant
      health. At the time the currentstudy began, most other studies had been
      conductedin the United States or Europe. Dr. Zhengmin Qianproposed to extend work
      he had done on ambientparticulate air pollution and daily mortality inWuhan,
      China (Qian et al. 2010), as part of the HEIsponsoredPublic Health and Air
      Pollution in Asiaprogram, to study adverse birth outcomes. Wuhan isthe capital
      city of Hubei province, has a large populationof about 6.4 million within the
      urban study area,experiences temperature extremes, and generally hashigher air
      pollution levels than those observed in theUnited States and Europe, thus
      providing a good opportunityto explore questions about air pollutionand health.
      Approach: Qian and colleagues planned a cohort and nestedcase-control design with
      four specific aims, examiningwhether increased exposures to air pollutants(PM2.5,
      PM10, SO2, NO2, O3, and CO) during vulnerablepregnancy periods were associated
      withincreased rates of PTB, LBW (<2500 g), or intrauterinegrowth retardation
      (IUGR, defined as havinga birth weight below the 10th percentile of singletonlive
      births in Wuhan) after adjusting for major riskfactors and whether the
      associations were confoundedby copollutant exposures, affected byresidual
      confounding, or modified by temperatureextremes, socioeconomic status (SES), or
      secondhandsmoke (SHS) exposure.The cohort study included 95,911 births
      thatoccurred from June 10, 2011, to June 9, 2013, andmet typical prespecified
      inclusion criteria used inother birth outcome studies. The case-controlstudy
      included 3146 cases (PTB, LBW, or both, butnot IUGR) and 4263 controls (matched
      to the casesby birth month) for whom investigators were able tocomplete home
      visits and questionnaires.The investigators obtained air pollution and
      dailyweather data for August 2010 to June 2013 from ninemonitoring stations
      representing background air pollutionsites in seven Wuhan inner-city districts.
      Onlytwo of these stations provided PM2.5 data. For thecohort study, the
      investigators assigned exposures tomothers according to the daily mean
      concentrationsfrom the monitor nearest the residential communityin which the
      mother lived at the time of the birth. Forthe case-control study, they assigned
      exposuresbased on the inverse distance weighted average ofdaily mean
      concentrations from the three nearestmonitors, for all but PM2.5 for which the
      method wasnot specified.They also collected data on various factors thatmight
      confound or modify the impact of the pollutantson the adverse outcomes, including
      data collectedin the cohort from mothers at the time of deliveryand, in the case
      control study, from questionnairesadministered to mothers. In the case-control
      study,covariates representing SES (as indicated by themother's educational
      attainment and household income)and SHS exposures were of particular interest.The
      primary statistical analyses of the pollutantassociations with PTB, LBW, and IUGR
      were conductedusing logistic regression models. In thecohort study, exposures
      during the pregnancyperiod of interest (full term, trimesters, and
      selectedmonths) were included as continuous variables. Inthe case-control study,
      the exposures were modeledas binary variables (i.e., above or below themedian
      pollutant concentrations). Numerous sensitivityanalyses were conducted. Results
      and interpretation: Although originally planning a nested case-controlstudy, the
      investigators encountered challenges thatled them to analyze the cohort and case
      controlstudies using different ways of assigning exposuresand characterizing them
      in their statistical models.These decisions precluded direct comparisonsbetween
      the sets of results, making it difficult toanswer the questions about residual
      confounding thatnested case-control studies are designed to answer.The odds
      ratios from the two study designs using differentexposures also have different
      interpretations.Still, one can ask whether the sets of findings werequalitatively
      consistent with each other or withthose of similar studies. There were some
      similarities.Both studies suggested that increased PM(2.5),PM(10), CO, and O(3)
      exposures over the full pregnancywere associated with small increases in the odds
      ofPTB (the case-control study also showed an associationwith NO2) and that
      increased PM(2.5) exposureswere associated with significantly increased odds
      ofLBW. However, most of the other pollutants had noeffect on LBW, except CO in
      the cohort study and O(3)in the case-control study, both of which increasedthe
      odds of LBW. The exposures over the entire pregnancywere generally associated
      with decreasedodds of IUGR. Adjustments for potential confounderswere greatest
      for the delivery covariates.The investigators found no systematic associationof
      any of these outcomes with particular trimestersor months, another result that
      differed fromthose of some other studies. They found little evidencethat their
      main results were confounded ormodified by the presence of copollutants,
      althoughwith the exception of O3, most of the pollutantswere highly correlated,
      making it difficult to disentanglethe effects of individual pollutants.Could the
      two sets of data be analyzed in a morecomparable way, as in a standard nested
      case-controlstudy? At the Committee's request, the investigatorsreanalyzed the
      case-control data using the sameexposures and models as in the cohort study.
      Theresults were strikingly different from those usingthe inverse distance
      weighted exposures, modeledas binary variables - the pollutants had either
      noeffect or an apparent beneficial effect on PTB andLBW. The Committee was not
      convinced by theexplanations offered for these differences, leavingthe reasons
      for them unresolved. Conclusions: This study set out to answer important
      questionsabout the effects of air pollution exposure on threemeasures of adverse
      birth outcomes - LBW, PTB,and IUGR - in a large cohort of mothers and newbornsin
      Wuhan, China. Given the cohort size, highpollution levels and temperatures, and
      detailedcovariate data, the investigators were well poised toaddress these
      questions. They sought to patterntheir work on other studies of birth outcomes,
      werevery responsive to Committee questions, and providedmany additional analyses
      and explanations.In the Committee's view, however, the study wasunable to address
      with confidence several of its specificaims. Most important, the differences
      inresults when the case-control data were analyzedwith different exposure metrics
      remain unexplained,raising concerns about the ability to drawconclusions from
      subsequent analyses assessingresidual confounding and effect modification
      bytemperature extremes, SES, and SHS exposure.Consequently, any individual
      findings from thecohort and case-control studies should be consideredsuggestive
      rather than conclusive, and shouldbe interpreted carefully together.

PMID- 29659241
TI  - Protective Role of Eosinophils and TNFa after Ozone Inhalation.
AB  - Introduction: Exposure to ozone induces deleterious responsesin the airways that
      include shortness of breath,inflammation, and bronchoconstriction. Peoplewith
      asthma have increased airway sensitivity toozone and other irritants. Dr. Allison
      Fryer andcolleagues addressed how exposure to ozone affectsthe immune and
      physiological responses inguinea pigs. Guinea pigs are considered a usefulanimal
      model for studies of respiratory and physiologicalresponses in humans; their
      response toairborne allergens is similar to that in humans andshares some
      features of allergic asthma.Fryer and colleagues had previously observedthat
      within 24 hours of exposure, ozone not onlyinduced bronchoconstriction but also
      stimulatedthe production of new cells in the bone marrow,where all white blood
      cells develop. As a resultof ozone exposure, increased numbers of
      newlysynthesized white blood cells, particularly eosinophils,moved into the blood
      and lungs.The central hypothesis of the current study wasthat newly synthesized
      eosinophils recruited tothe lungs 3 days after ozone exposure were beneficialto
      the animals because they reduced ozoneinducedbronchoconstriction. The
      investigatorsalso hypothesized that the beneficial effect seenin normal
      (nonsensitized) animals was lost in animalsthat had been injected with an
      allergen, ovalbumin(sensitized). They also planned to explorethe effects of
      inhibitors of certain cytokines (cellsignalingmolecules).Immune responses in
      sensitized animals aredominated by a Th2 pattern, which is characterizedby the
      synthesis of cytokines (interleukin[IL]-4, IL-5, and IL-13) and the Th2 subset of
      CD4+T lymphocytes and the cells they activate (predominantlyeosinophils, and B
      lymphocytes thatswitch to making immunoglobulin E [IgE]). Thus,sensitized animals
      were used as a model of allergichumans, whose immune responses tend to
      bedominated by IgE. Approach: Fryer and colleagues exposed normal and
      sensitized(allergic) guinea pigs to 2 ppm ozone or filteredair for 4 hours and
      measured changes in cellnumbers and airway responses 1 or 3 days later.They
      counted the numbers of eosinophils and otherwhite blood cells (macrophages,
      neutrophils, andlymphocytes) in bone marrow, blood, and bronchoalveolarlung
      lavage fluid. The investigatorsalso measured important physiological
      responses,including bronchoconstriction. Some animals werepretreated with
      etanercept and monoclonal anti-IL-5,which block tumor necrosis factor-a (TNFa)
      and IL-5,respectively. TNFa and IL-5 blockers have been usedto treat patients
      with asthma.A key feature of the study was a technique to distinguishwhich white
      blood cells were synthesized afterexposure from those that already existed, by
      injectinganimals with bromodeoxyuridine (BrdU). BrdUis a thymidine analogue that
      is incorporated into theDNA of dividing cells, serving as a marker of
      newlyproduced cells. Therefore, a snapshot can be obtainedof the proportion of
      newly synthesized (BrdU-positive)versus pre-existing (BrdU-negative) cell types.
      Key results: 1. Allergic and normal animals differed in the timecourse of
      bronchoconstriction and changes in celltypes after ozone exposure. In normal
      animals,bronchoconstriction increased substantially atday 1 but decreased by day
      3 after ozone exposure.In contrast, in allergic animals
      bronchoconstrictionremained high at day 3. Ozone also increasedthe percentage of
      newly formed, BrdU2positive eosinophils in the bone marrow andlungs of normal but
      not allergic animals.2. Pretreatment with the TNFa blocker etanercepthad complex
      effects, which differed betweennormal and allergic animals. In normal
      animals,etanercept decreased ozone-induced new synthesisof eosinophils in the
      bone marrow andblocked eosinophil migration to the lung; it alsoincreased
      bronchoconstriction at day 3 (relativeto day 1 without etanercept). In allergic
      animals,etanercept had no effect on any cell type in thebone marrow or lung after
      exposure to ozone anddid not change bronchoconstriction comparedwith allergic
      animals not treated with etanercept.Etanercept tended to increase the numbers
      ofblood monocytes and lymphocytes in air- andozone-exposed normal and allergic
      animals atday 3, but had no effect on eosinophils in bloodat this time point.
      This was one of the few statisticallysignificant findings in the blood of
      exposedanimals in the study.3. Anti-IL-5 reduced bronchoconstriction at day 3
      afterexposure of allergic animals to ozone. In contrast,bronchoconstriction was
      greatly increasedin normal animals treated with anti-IL-5. Conclusions: Fryer and
      colleagues explored the airway and cellularresponses in guinea pigs exposed to
      ozone. TheHEI Review Committee, which conducted an independentreview of the
      study, agreed that the findingssupported the authors' hypothesis (1) that
      exposureto ozone stimulates production of eosinophils in bonemarrow, (2) that
      these newly formed eosinophils migrateto the lungs, and (3) that those
      eosinophils playa delayed but potentially beneficial role in reducingozone
      induced inflammation in the airways of healthynormal animals, but not in allergen
      sensitized animals.The Committee also agreed that guinea pigswere a good model
      for studying responses to an allergen,because a major subtype of asthma (the
      highTh2 or allergic type) is associated with high levels ofeosinophils in the
      blood.A novel finding was that the TNFa blocker etanerceptdecreased ozone-induced
      formation of eosinophilsin the bone marrow and blocked eosinophilmigration to the
      lung in normal animals. However,because injecting etanercept had little effect on
      eosinophilsand did not decrease bronchoconstriction inallergic guinea pigs, the
      potential for treating patientswith allergic asthma with TNFa blockers is
      uncertain.This is consistent with the poor performance of TNFablockers in
      clinical studies of asthma treatment.Blocking the cytokine IL-5 with an anti-IL-5
      antibodysubstantially decreased bronchoconstriction insensitized animals. This
      suggests that therapies targetingIL-5 and eosinophils would be promising in
      atleast some types of asthma. The Committee expressedcaution toward experiments
      with cytokine blockers,both in animal models and humans, because suchblockers are
      often not specific to a particular cell typeand may differ at different sites in
      the body. Withoutfurther detailed confirmation of the effects of theblockers,
      interpreting these experiments can be challenging.The Committee concluded that
      the study by Fryerand colleagues raises several intriguing directions forfuture
      research, including exploring ways in whichnewly formed eosinophils differ from
      pre-existingones, and how such findings apply to humans withallergy or asthma.

PMID- 29659242
TI  - Exploring the Promiscuity of Phenol Hydroxylase from Pseudomonas stutzeri OX1 for
      the Biosynthesis of Phenolic Compounds.
AB  - Enzyme promiscuity plays an important role in developing biosynthetic pathways
      for novel target products. Phenol hydroxylase (PH) from Pseudomonas stutzeri OX1
      is capable of ortho-hydroxylation of phenol and cresol isomers into counterpart
      catechols. A small ferredoxin-like protein PHQ was clustered together with the ph
      gene cluster in the genome of P. stutzeri OX1, and its function was not known. In
      this study, we found that the existence of PHQ has a promotion effect on the
      catalytic efficiency of PH. Then, we tested the substrate range of PH using nine
      different non-natural substrates. We found that PH was a promiscuous hydroxylase
      that could catalyze ortho-hydroxylation of several non-natural substrates,
      including catechol, 4-hydroxybenzoic acid and resorcinol. On this basis, linking
      the catechol biosynthetic pathway with the hydroxylation reaction catalyzed by PH
      enabled construction of a novel biosynthetic pathway for the synthesis of
      pyrogallol. This work not only characterized a well-performed PH, but also
      provided a promising hydroxylation platform for the production of high-value
      phenolic compounds.

PMID- 29659243
TI  - Carbonization of Human Fingernails: Toward the Sustainable Production of
      Multifunctional Nitrogen and Sulfur Codoped Carbon Nanodots with Highly
      Luminescent Probing and Cell Proliferative/Migration Properties.
AB  - A simple yet effective method is employed to prepare multifunctional fluorescent
      carbon nanodots (CNDs) from human fingernails. The results demonstrate that the
      CNDs have excellent optical properties and a quantum yield of 81%, which is
      attributed to the intrinsic composition of the precursor material itself. The
      CNDs are used to develop an ultrasensitive fluorescent probe for the detection of
      hexavalent chromium (limit of detection: 0.3 nM) via a combined inner-filter and
      static mechanism. Moreover, the toxicity of the CNDs over four epithelial cell
      lines is assessed. A negligible toxicity is induced on the three of the cell
      lines, whereas an increase in HEK-293 cell viability is demonstrated, granting
      cell proliferation properties to the as-synthesized CNDs. According to cell cycle
      analysis, cell proliferation is achieved by enhancing the transition of cells
      from the S phase to the G2/M one. Interestingly, CNDs are found to significantly
      promote cell migration, maybe because of their free-radical scavenging ability,
      making the CNDs suitable for wound healing applications. In addition, relevant
      experiments have revealed the blood compatibility of the CNDs. Finally, the CNDs
      were found suitable for cell imaging applications, and all of the aforementioned
      merits make it possible for them to be used for extraordinary, more advanced
      biological applications.

PMID- 29659244
TI  - Chemical Mapping of Nanodefects within 2D Covalent Monolayers by Tip-Enhanced
      Raman Spectroscopy.
AB  - Nanoscale defects in monolayers (MLs) of two-dimensional (2D) materials, such as
      graphene, transition-metal dichalcogenides, and 2D polymers, can alter their
      physical, mechanical, optoelectronic, and chemical properties. However, detailed
      information about nanodefects within 2D covalent monolayers is difficult to
      obtain because it requires highly selective and sensitive techniques that can
      provide chemical information at the nanoscale. Here, we report a 2D imine-linked
      ML prepared from two custom-designed building blocks by dynamic imine chemistry
      at the air/water interface, in which an acetylenic moiety in one of the blocks
      was used as a spectroscopic reporter for nanodefects. Combined with density
      functional theory calculations that take into account surface selection rules,
      tip-enhanced Raman spectroscopy (TERS) imaging provides information on the
      chemical bonds, molecular orientation, as well as nanodefects in the resulting
      ML. Additionally, TERS imaging visualizes the topography and integrity of the ML
      at Au(111) terrace edges, suggesting possible ductility of the ML. Furthermore,
      edge-induced molecular tilting and a stronger signal enhancement were observed at
      the terrace edges, from which a spatial resolution around 8 nm could be deduced.
      The present work can be used to study covalent 2D materials at the nanoscale,
      which are expected to be of use when engineering their properties for specific
      device applications.

PMID- 29659245
TI  - Mechanisms of Enhanced Hemoglobin Electroactivity on Carbon Electrodes upon
      Exposure to a Water-Miscible Primary Alcohol.
AB  - Exposing a carbon electrode to hemoglobin (Hb) and alcoholic solvents, such as
      methanol, ethanol or 1-propanol, drastically changes Hb electroactivity, but
      until this work, the important underlying mechanisms were unclear. For the first
      time, we show that these alcohols impact Hb electroactivity via three mechanisms:
      modification of the carbon surface oxides on the glassy carbon (GC) electrode, Hb
      film formation, and structural changes to Hb. C1s X-ray photoelectron
      spectroscopy provided evidence for significant alcohol-induced modification of
      the carbon surface oxides, and differential pulse voltammetry showed links
      between these modifications and Hb electroactivity. Spectroscopic ellipsometry
      showed that Hb films formed during exposure to Hb- and alcohol-containing
      electrolytes increased in thickness with increasing alcohol content, although
      film thickness played only a minor role in Hb electroactivity. Alcohol-induced
      structural changes in Hb are confirmed with UV-visible absorption and
      fluorescence data, showing that Hb denaturation also was a significant factor in
      increasing Hb electroactivity. Carbon-surface-oxide modification and Hb
      denaturation worked in tandem to maximally increase the Hb electroactivity in 60%
      methanol. While in ethanol and 1-propanol, the significant increases in Hb
      electroactivity caused by Hb denaturation were offset by an increase in Hb
      inhibiting carbon surface oxides. Knowledge of these mechanisms shows the impact
      of alcohols on both Hb and carbon electrodes, allows for thoughtful design of the
      Hb-sensing system, is vital for proper analysis of Hb electroactivity in the
      presence of these alcohols (e.g., when used as binder solvents for immobilizing
      Hb into films), and provides fundamental understanding of the Hb-carbon
      interactions.

PMID- 29659246
TI  - Membrane Nanotubes Increase the Robustness of Giant Vesicles.
AB  - Giant unilamellar vesicles (GUVs) provide a direct connection between the nano-
      and the microregime. On the one hand, these vesicles represent biomimetic
      compartments with linear dimensions of many micrometers. On the other hand, the
      vesicle walls are provided by single molecular bilayers that have a thickness of
      a few nanometers and respond sensitively to molecular interactions with small
      solutes, biopolymers, and nanoparticles. These nanoscopic responses are amplified
      by the GUVs and can then be studied on much larger scales. Therefore, GUVs are
      increasingly used as a versatile research tool for basic membrane science,
      bioengineering, and synthetic biology. Conventional GUVs have one major drawback,
      however: they have only a limited capability to cope with external perturbations
      such as osmotic inflation, adhesion, or micropipette aspiration that tend to
      rupture the membranes. In contrast, cell membranes tolerate the same kinds of
      mechanical perturbations without rupture because the latter membranes are coupled
      to reservoirs of membrane area. Here, we introduce GUVs with membrane nanotubes
      as model systems that include such area reservoirs. To demonstrate the increased
      robustness of these tubulated vesicles, we use micropipette aspiration and
      changes in the osmotic conditions applied to phospholipid membranes doped with
      the glycolipid GM1. A quantitative comparison between theory and experiment
      reveals that the response of the GUVs is governed by the membranes' spontaneous
      tension, a curvature-elastic material parameter that describes the bilayer
      asymmetry on the nanoscale. Because of their increased robustness, GUVs with
      nanotubes represent improved research tools for membrane science, in general,
      with potential applications as storage and delivery systems and as cell-like
      microcompartments in bioengineering, pharmacology, and synthetic biology.

PMID- 29659247
TI  - Computational Design of High-chi Block Oligomers for Accessing 1 nm Domains.
AB  - Molecular dynamics simulations are used to design a series of high-chi block
      oligomers (HCBOs) that can self-assemble into a variety of mesophases with domain
      sizes as small as 1 nm. The exploration of these oligomers with various chain
      lengths, volume fractions, and chain architectures at multiple temperatures
      reveals the presence of ordered lamellae, perforated lamellae, and hexagonally
      packed cylinders. The achieved periods are as small as 3.0 and 2.1 nm for
      lamellae and cylinders, respectively, which correspond to polar domains of
      approximately 1 nm. Interestingly, the detailed phase behavior of these oligomers
      is distinct from that of either solvent-free surfactants or block polymers. The
      simulations reveal that the behavior of these HCBOs is a product of an interplay
      between both "surfactant factors" (headgroup interactions, chain flexibility, and
      interfacial curvature) and "block polymer factors" (chi, chain length N, and
      volume fraction f). This insight promotes the understanding of molecular features
      pivotal for mesophase formation at the sub-5 nm length scale, which facilitates
      the design of HCBOs tailored toward particular desired morphologies.

PMID- 29659248
TI  - SnO2@C@VO2 Composite Hollow Nanospheres as an Anode Material for Lithium-Ion
      Batteries.
AB  - Porous SnO2@C@VO2 composite hollow nanospheres were ingeniously constructed
      through the combination of layer-by-layer deposition and redox reaction.
      Moreover, to optimize the electrochemical properties, SnO2@C@VO2 composite hollow
      nanospheres with different contents of the external VO2 were also studied. On the
      one hand, the elastic and conductive carbon as interlayer in the SnO2@C@VO2
      composite can not only buffer the huge volume variation during repetitive cycling
      but also effectively improve electronic conductivity and enhance the utilizing
      rate of SnO2 and VO2 with high theoretical capacity. On the other hand, hollow
      nanostructures of the composite can be consolidated by the multilayered
      nanocomponents, resulting in outstanding cyclic stability. In virtue of the above
      synergetic contribution from individual components, SnO2@C@VO2 composite hollow
      nanospheres exhibit a large initial discharge capacity (1305.6 mAhg-1) and
      outstanding cyclic stability (765.1 mAhg-1 after 100 cycles). This design of
      composite hollow nanospheres may be extended to the synthesis of other
      nanomaterials for electrochemical energy storage.

PMID- 29659249
TI  - Analysis of Crystalline Silica Aerosol Using Portable Raman Spectrometry:
      Feasibility of Near Real-Time Measurement.
AB  - A Raman spectroscopy based method has been developed for measurement of trace
      airborne concentrations of respirable crystalline silica (RCS) using various
      aerosol sampling and analysis techniques. Three aerosol microconcentration
      techniques were investigated for effective coupling of collected particulate
      samples with micro-Raman spectroscopy: (i) direct analysis on a particulate
      filter after focused aerosol collection using a converging nozzle; (ii) analysis
      of dried particulate deposit on a filter obtained directly from the aerosol phase
      using the Spotsampler device; and (iii) analysis of a dried spot (~1-3 mm
      diameter) obtained by redepositing the particulate sample, after low-temperature
      plasma ashing of the filter sample. The deposition characteristics (i.e., spot
      diameter, shape, and deposit uniformity) of each technique were investigated.
      Calibration curves were constructed and detection limits were estimated for alpha
      quartz using the A1 Raman Si-O-Si stretching-bending phonon mode at 465 cm-1. The
      measurement sensitivity could be substantially improved by increasing the signal
      integration time and by reducing the particle deposition area. Detection limits
      in the range of 8-55 ng could be achieved by microconcentrating the aerosol
      sample over a spot measuring 400-1000 MUm in diameter. These detection limits
      were two to three orders of magnitude lower compared to those attainable using
      current standardized X-ray diffraction and infrared spectroscopy methods. The low
      detection limits suggest that near real-time measurements of RCS could be
      achieved with limits of quantification ranging from 2 to 18.5 MUg/m3 (at 10 min
      collection time and 1.2 L/min sampling flow rate), depending on
      microconcentration technique used. The method was successfully extended to the
      measurement of alpha-quartz air concentration in representative workplace aerosol
      samples. This study demonstrates the potential of portable micro-Raman
      spectroscopy for near-real time measurement of trace RCS in air.

PMID- 29659250
TI  - Concurrent Harvesting of Ambient Energy by Hybrid Nanogenerators for Wearable
      Self-Powered Systems and Active Remote Sensing.
AB  - Harvesting energy available from ambient environment is highly desirable for
      powering personal electronics and health applications. Due to natural process and
      human activities, steam can be produced by boilers, human perspiration, and the
      wind exists ubiquitously. In the outdoor environment, these two phenomena usually
      exist at the same place, which contain heat and mechanical energies
      simultaneously. However, previous studies have isolated them as separate sources
      of energy to harvest and hence failed to utilize them effectively. Herein, we
      present unique hybrid nanogenerators for individually/simultaneously harvesting
      thermal energy from water vapors and mechanical energy from intermittent wind
      blowing from the bottom side, which consist of a wind-driven triboelectric
      nanogenerator (TENG) and pyroelectric-piezoelectric nanogenerators (PPENGs). The
      output power of the PPENG and the TENG can be up to about 184.32 MUW and 4.74 mW,
      respectively, indicating the TENG plays the dominant role. Our hybrid
      nanogenerators could provide different applications such as to power digital
      watch and enable self-powered sensing with wireless transmission. The device
      could also be further integrated into a face mask for potentially wearable
      applications. This work not only provides a promising approach for renewable
      energy harvesting but also enriches potential applications for self-powered
      systems and wireless sensors.

PMID- 29659251
TI  - Enhancing the Strength of Graphene by a Denser Grain Boundary.
AB  - From a device application point of view, the extreme mechanical strength of
      graphene is highly desirable. However, the unavoidable polycrystalline nature of
      graphene films produced by chemical vapor deposition (CVD) leads to significant
      fluctuations in mechanical properties. Although the effects of atomic defects or
      grain boundaries (GBs) on mechanical strength have been widely studied and some
      modifications have been applied to enhance the stiffness of graphene, the
      problems of fragility as well as significantly reduced breaking strength arise.
      Here we report a systematic study on the effect of elastic modulus and breaking
      strength of CVD-derived graphene films with a controlled density and distribution
      of GBs. We find that graphene films become much stronger by hugely increasing the
      density of GBs without triple junctions (TJs) formed inside, in analogy to the
      two-dimensional (2D) plum pudding structures. The comprehensive performance with
      a 2D Young's modulus of 436 N/m (~1.3 TPa) and 2D breaking strength of 43 N/m
      (~128 GPa) can be achieved with the average grain size of 20 nm. Moreover, the
      existence of TJs will slightly reduce the strength in these GB structures. Due to
      defect types, the graphene films will show various tearing behaviors after
      indentation. All these mechanical studies of GBs provide a guideline to obtain
      the optimal performance of 2D materials through GB structure engineering.

PMID- 29659252
TI  - Poly(vinyl alcohol)-Assisted Fabrication of Hollow Carbon Spheres/Reduced
      Graphene Oxide Nanocomposites for High-Performance Lithium-Ion Battery Anodes.
AB  - Three-dimensional hollow carbon spheres/reduced graphene oxide (DHCSs/RGO)
      nanocomposites with high-level heteroatom doping and hierarchical pores are
      fabricated via a versatile method. Poly(vinyl alcohol) (PVA) that serves as a
      dispersant and nucleating agent is used as the nonremoval template for
      synthesizing melamine resin (MR) spheres with abundant heteroatoms, which are
      subsequently composited with graphene oxide (GO). Use of PVA and implementation
      of freezing treatment prevent agglomeration of MR spheres within the GO network.
      Molten KOH is used to achieve the one-step carbonization/activation/reduction for
      the synthesis of DHCSs/RGO. DHCSs/RGO annealed at 700  degrees C shows superior
      discharge capacity of 1395 mA h/g at 0.1 A/g and 606 mA h/g at 5 A/g as well as
      excellent retentive capacity of 755 mA h/g after 600 cycles at a current density
      of 2 A/g. An extra CO2 activation leads to further enhancement of electrochemical
      performance with outstanding discharge capacity of 1709 mA h/g at 0.1 A/g and 835
      mA h/g at 2 A/g after 600 cycles. This work may improve our understanding of the
      synthesis of graphene-like nanocomposites with hollow and porous carbon
      architectures and fabrication of high-performance functional devices.

PMID- 29659253
TI  - Novel Sulfonated Co-poly(ether imide)s Containing Trifluoromethyl, Fluorenyl and
      Hydroxyl Groups for Enhanced Proton Exchange Membrane Properties: Application in
      Microbial Fuel Cell.
AB  - A hydroxyl group containing new cardo diamine monomer was synthesized, namely 9,9
      bis (hydroxy- (4'-amino(3-trifluoromethyl)biphenyl-4-oxy)-phenyl)-9H-fluorene
      (mixture of isomers, HAPHPF). HAPHPF, along with a sulfonated diamine monomer,
      4,4'-diaminostilbene-2,2'-disulfonic acid (DSDSA), was used to prepare a series
      of new sulfonated copolyimides by polycondensation with 1,4,5,8
      naphthalenetetracarboxylic dianhydride (NTDA). The degree of sulfonation (DS < 1)
      was adjusted by the feed ratio of DSDSA/HAPHPF and the copolymers were named as
      DHN-XX, where XX denotes the mole percentage of DSDSA (XX = 50, 60, and 70). The
      copolymers showed high molecular weights. The copolymer structure and composition
      were confirmed by FTIR and NMR techniques. Copolymer membranes were prepared
      through solution cast route by using dimethyl sulfoxide as a solvent. The
      membranes showed high thermal, mechanical, hydrolytic and peroxide radical
      stability, and low water uptake and low swelling ratios. Well-separated
      hydrophilic and hydrophobic phase morphology was observed in TEM and AFM images
      of the copolymer membranes and was further supported by the SAXS studies. The
      proton conductivity of the DHN-70 was as high as 97 mS cm-1 at 80  degrees C and
      the value is significantly higher than that of the nonhydroxylated analogue. The
      membranes also showed superior microbial fuel cell (MFC) performance, similar
      like Nafion 117 under similar test conditions. The chemical oxygen demand removal
      values provide substantial evidence that the fabricated membranes can be utilized
      in bioelectrochemical systems.

PMID- 29659254
TI  - Occurrence and Distribution of Organophosphate Flame Retardants/Plasticizers in
      Surface Waters, Tap Water, and Rainwater: Implications for Human Exposure.
AB  - The occurrence and profiles of 14 triester organophosphate flame retardants
      (OPFRs) and plasticizers were investigated in surface water, tap water,
      rainwater, and seawater collected from New York State. In total, 150 samples
      collected from rivers ( n = 35), lakes ( n = 39), tap water ( n = 58),
      precipitation/rainwater ( n = 15), and seawater ( n = 3) were analyzed for 14
      organophosphate esters (OPEs). An additional nine Hudson River water samples were
      collected periodically to delineate seasonal trends in OPE levels. The total
      concentrations of OPEs were found at part-per-trillion ranges, with average
      concentrations that ranged from 0.01 ng/L for tripropyl phosphate (TPP) in river
      water to 689 ng/L for tris(2-butoxyethyl)phosphate (TBOEP) in lake water. Tris(1
      chloro-2-propyl)phosphate (TCIPP) was the most abundant compound among the
      investigated OPEs in all types of water. The concentrations of OPEs in river-,
      lake-, and rainwater were similar but >3 times higher than those found in tap
      water. Chlorinated alkyl OPFRs accounted for a major proportion of total
      concentrations. TCIPP, TBOEP, and triethyl phosphate (TEP) were found in >90% of
      the samples analyzed. Wet deposition fluxes for 14 OPFRs were estimated, on the
      basis of the concentrations measured in rainwater in Albany, New York, and the
      values were between 440 and 5250 ng/m2. Among several surface water bodies
      analyzed, samples from the Hudson River and Onondaga Lake contained elevated
      concentrations of OPEs. Estimated daily intake of OPEs via the ingestion of
      drinking water was up to 9.65 ng/kg body weight/day.

PMID- 29659255
TI  - Stimulation of Innate Immune Function by Panax ginseng after Heat Processing.
AB  - Panax ginseng Meyer has been used for the treatment of immune diseases and for
      strengthening the immune function. In this study, we evaluated the innate immune
      stimulating functions and action mechanisms of white ginseng (WG) and heat
      processed ginseng (HPG) in RAW264.7 cells. According to LC-MS analysis results,
      WG contained typical ginsenosides, such as Rb1, Rc, Rb2, Rd, and Rg1, whereas HPG
      contained Rg3, Rk1, and Rg5 as well as typical ginsenosides. HPG, not WG,
      enhanced NF-kappaB transcriptional activity, cytokine production (IL-6 and TNF
      alpha), and MHC class I and II expression in RAW264.7 cells. In addition, HPG
      phosphorylated MAPKs and NF-kB pathways. In experiments with inhibitors, the ERK
      inhibitor completely suppressed the effect of HPG on IL-6 and TNF-alpha
      production. HPG-induced c-Jun activation was suppressed by an ERK inhibitor and
      partially suppressed by JNK, p38, and IkappaBalpha inhibitors. Collectively,
      these results suggested that HPG containing Rg3, Rg5, and Rk1 increased
      macrophage activation which was regulated by the ERK/c-Jun pathway in RAW264.7
      cells.

PMID- 29659256
TI  - Initial Biochemical and Functional Evaluation of Murine Calprotectin Reveals
      Ca(II)-Dependence and Its Ability to Chelate Multiple Nutrient Transition Metal
      Ions.
AB  - Calprotectin (CP) is an abundant host-defense protein that contributes to the
      metal-withholding innate immune response by sequestering nutrient metal ions from
      microbial pathogens in the extracellular space. Over the past decade, murine
      models of infectious disease have advanced understanding of the physiological
      functions of CP and its ability to compete with microbes for essential metal
      nutrients. Despite this extensive work, murine CP (mCP) has not been
      biochemically evaluated, and structural and biophysical understanding of CP is
      currently limited to the human orthologue. We present the reconstitution,
      purification, and characterization of mCP as well as the cysteine-null variant
      mCP-Ser. Apo mCP is a mS100A8/mS100A9 heterodimer, and Ca(II) binding causes two
      heterodimers to self-associate and form a heterotetramer. Initial metal-depletion
      studies demonstrate that mCP depletes multiple first-row transition metal ions,
      including Mn, Fe, Ni, Cu, and Zn, from complex microbial growth medium,
      indicating that mCP binds multiple nutrient metals with high affinity. Moreover,
      antibacterial activity assays show that mCP inhibits the growth of a variety of
      bacterial species. The metal-depletion and antibacterial activity studies also
      provide evidence that Ca(II) ions enhance these functional properties of mCP.
      This contribution provides the groundwork for understanding the similarities and
      differences between the human and murine orthologues of CP and for further
      elucidation of its biological coordination chemistry.

PMID- 29659258
TI  - Oil Spills and Dispersants Can Cause the Initiation of Potentially Harmful
      Dinoflagellate Blooms ("Red Tides").
AB  - After oil spills and dispersant applications the formation of red tides or
      harmful algal blooms (HABs) has been observed, which can cause additional
      negative impacts in areas affected by oil spills. However, the link between oil
      spills and HABs is still unknown. Here, we present experimental evidence that
      demonstrates a connection between oil spills and HABs. We determined the effects
      of oil, dispersant-treated oil, and dispersant alone on the structure of natural
      plankton assemblages in the Northern Gulf of Mexico. In coastal waters, large
      tintinnids and oligotrich ciliates, major grazers of phytoplankton, were
      negatively affected by the exposure to oil and dispersant, whereas bloom-forming
      dinoflagellates ( Prorocentrum texanum, P. triestinum, and Scrippsiella
      trochoidea) notably increased their concentration. The removal of key grazers due
      to oil and dispersant disrupts the predator-prey controls ("top-down controls")
      that normally function in plankton food webs. This disruption of grazing pressure
      opens a "loophole" that allows certain dinoflagellates with higher tolerance to
      oil and dispersants than their grazers to grow and form blooms when there are no
      growth limiting factors (e.g., nutrients). Therefore, oil spills and dispersants
      can act as disrupters of predator-prey controls in plankton food webs and as
      indirect inducers of potentially harmful dinoflagellate blooms.

PMID- 29659257
TI  - Diurnal Variability and Emission Pattern of Decamethylcyclopentasiloxane (D5)
      from the Application of Personal Care Products in Two North American Cities.
AB  - Decamethylcyclopentasiloxane (D5) is a cyclic volatile methyl siloxane (cVMS)
      that is widely used in consumer products and commonly observed in urban air. This
      study quantifies the ambient mixing ratios of D5 from ground sites in two North
      American cities (Boulder, CO, USA, and Toronto, ON, CA). From these data, we
      estimate the diurnal emission profile of D5 in Boulder, CO. Ambient mixing ratios
      were consistent with those measured at other urban locations; however, the
      diurnal pattern exhibited similarities with those of traffic-related compounds
      such as benzene. Mobile measurements and vehicle experiments demonstrate that
      emissions of D5 from personal care products are coincident in time and place with
      emissions of benzene from motor vehicles. During peak commuter times, the
      D5/benzene ratio (w/w) is in excess of 0.3, suggesting that the mass emission
      rate of D5 from personal care product usage is comparable to that of benzene due
      to traffic. The diurnal emission pattern of D5 is estimated using the measured
      D5/benzene ratio and inventory estimates of benzene emission rates in Boulder.
      The hourly D5 emission rate is observed to peak between 6:00 and 7:00 AM and
      subsequently follow an exponential decay with a time constant of 9.2 h. This
      profile could be used by models to constrain temporal emission patterns of
      personal care products.

PMID- 29659259
TI  - Exploring Lanthanide Doping in UiO-66: A Combined Experimental and Computational
      Study of the Electronic Structure.
AB  - Lanthanide-based metal-organic frameworks show very limited stabilities, which
      impedes their use in applications exploiting their extraordinary electronic
      properties, such as luminescence and photocatalysis. This study demonstrates a
      fast and easy microwave procedure to dope UiO-66, an exceptionally stable and
      tunable Zr-based metal-organic framework. The generally applicable synthesis
      methodology is used to incorporate different transition metal and lanthanide
      ions. Selected experiments on these newly synthesized materials allow us to
      construct an energy scheme of lanthanide energy levels with respect to the UiO-66
      host. The model is confirmed via absolute intensity measurements and provides an
      intuitive way to understand charge transfer mechanisms in these doped UiO-66
      materials. Density functional theory calculations on a subset of materials
      moreover improve our understanding of the electronic changes in doped UiO-66 and
      corroborate our empirical model.

PMID- 29659260
TI  - Critical Problems Stalling Progress in Natural Bioactive Polysaccharide Research
      and Development.
AB  - Natural polysaccharides are attracting increasing attention from food and
      pharmaceutical industries for their wide range of valuable biological activities.
      However, the poor repeatability of the methods used in sample preparation and
      chemical characterization is hampering both research and product development. The
      unstandardized quality, in turn, undermines efforts to understand the mechanism
      by which they work via oral dose, which is essential to realize the full
      beneficial potential of polysaccharides. Some scientists believe polysaccharides
      work by direct gut absorption; however, increasing evidence points to the gut
      microbiome and intestinal Peyer's patches as holding the keys to how they work.

PMID- 29659261
TI  - Three Cd(II) MOFs with Different Functional Groups: Selective CO2 Capture and
      Metal Ions Detection.
AB  - Three Cd(II) iso-frameworks {[Cd(BIPA)(IPA)].DMF} n (1), {[Cd(BIPA)(HIPA)].DMF} n
      (2), and {[Cd(BIPA)(NIPA)].2H2O} n (3) were synthesized from the self-assembly of
      the BIPA ligand (BIPA = bis(4-(1 H-imidazol-1-yl)phenyl)amine) and different
      carboxylic ligands (H2IPA = isophthalic acid, H2HIPA = 5-hydroxyisophthalic acid,
      H2NIPA = 5-nitroisophthalic acid) with Cd(II), which have amino groups, amino and
      phenolic hydroxyl groups, and amino and nitro groups, respectively. Both 1 and 2
      exhibit CO2 uptakes of more than 20 wt %, indicating that amino and phenolic
      hydroxyl functionalized groups are beneficial to CO2 adsorption. Their
      applications and mechanisms in detecting metal ions were researched. The results
      exhibit that 1 and 2 are dual-responsive photoluminescent sensors for Hg2+ and
      Pb2+ ions with low detection concentration and high quenching constant. Besides,
      like most MOFs, 3 can detect a trace quantity of Fe3+ and Cu2+.

PMID- 29659262
TI  - Fluorescent BODIPY-Anionic Boron Cluster Conjugates as Potential Agents for Cell
      Tracking.
AB  - A series of novel fluorescent BODIPY-anionic boron cluster conjugates bearing
      [B12H12]2- (5, 6), [3,3'-Co(1,2-C2B9H11)2]- (7, 8), and [3,3'-Fe(1,2-C2B9H11)2]-
      (9) anions have been readily synthesized from meso-(4-hydroxyphenyl)-4,4-difluoro
      4-bora-3 a,4 a-diaza- s-indacene (BODIPY 4), and their structure and
      photoluminescence properties have been assessed. Linking anionic boron clusters
      to the BODIPY (4) does not alter significantly the luminescent properties of the
      final fluorophores, showing all of them similar emission fluorescent quantum
      yields (3-6%). Moreover, the cytotoxicity and cellular uptake of compounds 5-9
      have been analyzed in vitro at different concentrations of B (5, 50, and 100 MUg
      B/mL) using HeLa cells. At the lowest concentration, none of the compounds shows
      cytotoxicity and they are successfully internalized by the cells, especially
      compounds 7 and 8, which exhibit a strong cytoplasmic stain indicating an
      excellent internalization efficiency. To the best of our knowledge, these are the
      first BODIPY-anionic boron cluster conjugates developed as fluorescent dyes
      aiming at prospective biomedical applications. Furthermore, the cellular
      permeability of the starting BODIPY (4) was improved after the functionalization
      with boron clusters. The exceptional cellular uptake and intracellular boron
      release, together with the fluorescent and biocompatibility properties, make
      compounds 7 and 8 good candidates for in vitro cell tracking.

PMID- 29659263
TI  - Secondary Oxide Phosphines to Promote Tandem Acyl-Alkyl Coupling/Hydrogen
      Transfer to Afford (Hydroxyalkyl)rhodium Complexes. Theoretical and Experimental
      Studies.
AB  - Acyl(sigma-norbornenyl)rhodium(III) dimer [Rh(MU-Cl)(C9H6NCO)(C7H9)L]2 (1) (C7H9
      = sigma-norbornenyl; L = 4-picoline, isoquinoline) reacts with diphenylphosphine
      oxide (SPO) to undergo a one-pot reaction involving (i) cleavage of the chloride
      bridges and coordination of the phosphine, (ii) C-C bond coupling between acyl
      and norbornenyl in a 18e species, and (iii) ligand-assisted outer-sphere O(P)-to
      O(C) hydrogen transfer, to afford mononuclear 16e species
      [RhCl{(C9H6NC(O)C7H9)(Ph2PO)H}(L)] (2) containing a quinolinyl
      (norbornenylhydroxyalkyl) fragment hydrogen-bonded to a kappa1- P-phosphinite
      ligand. Pentacoordinated 2, which adopt a distorted trigonal bipyramidal
      structure, are kinetic reaction products that transform into the thermodynamic
      favored isomers 3. Structures 3 contain an unusual weak eta1-C anagostic
      interaction involving the rhodium atom and one carbon atom of the olefinic C-H
      bond of the norbornenyl substituent in the chelating quinolinyl-hydroxyalkyl
      moiety. Their structure can be described as pseudoctahedral, through a 5 + 1
      coordination, with the anagostic interaction in a trans disposition with respect
      to the phosphorus atom of the phosphinite ligand. Complexes were characterized in
      solution by NMR spectroscopy and electrospray ionization mass spectrometry.
      Complex [RhCl{(C9H6NC(O)C7H9)(Ph2PO)H}(4-picoline)] (3a) was also identified by X
      ray diffraction. Density functional theory calculations confirm the proposed
      structures by a plausible set of mechanisms that accounts for the 1 (monomer) ->
      2 -> 3 transformation. Lowest-energy pathways involve reductive elimination of
      quinolinylnorbornenylketone, still coordinated in the rhodium(I) species thus
      formed, followed by O-to-O hydrogen transfer from kappa1- P-SPO to the sp3
      hybridized carbonyl group (formal alkoxide) avoiding the otherwise expected
      classical release of ketone. Theoretical 13C NMR studies also confirm the
      experimental spectral data for the considered structures.

PMID- 29659264
TI  - Kinetics and Mechanism of Oxirane Formation by Darzens Condensation of Ketones:
      Quantification of the Electrophilicities of Ketones.
AB  - The kinetics of epoxide formation by Darzens condensation of aliphatic ketones 1
      with arylsulfonyl-substituted chloromethyl anions 2 (ArSO2CHCl-) have been
      determined photometrically in DMSO solution at 20  degrees C. The reactions
      proceed via nucleophilic attack of the carbanions at the carbonyl group to give
      intermediate halohydrin anions 4, which subsequently cyclize with formation of
      the oxiranes 3. Protonation of the reaction mixture obtained in THF solution at
      low temperature allowed the intermediates to be trapped and the corresponding
      halohydrins 4-H to be isolated. Crossover experiments, i.e., deprotonation of the
      halohydrins 4-H in the presence of a trapping reagent for the regenerated
      arylsulfonyl-substituted chloromethyl anions 2, provided the relative rates of
      backward ( k-CC) and ring closure ( krc) reactions of the intermediates.
      Combination of the kinetic data ( k2exptl) with the splitting ratio ( k-CC/ krc)
      gave the second-order rate constants kCC for the attack of the carbanions 2 at
      the ketones 1. These kCC values and the previously reported reactivity parameters
      N and sN for the arylsulfonyl-substituted chloromethyl anions 2 allowed us to use
      the linear free energy relationship log k2(20  degrees C) = sN( N + E) for
      deriving the electrophilicity parameters E of the ketones 1 and thus predict
      potential nucleophilic reaction partners. Density functional theory calculations
      of the intrinsic reaction pathways showed that the reactions of the ketones 1
      with the chloromethyl anions 2 yield two rotational isomers of the intermediate
      halohydrin anions 4, only one of which can cyclize while the other undergoes
      retroaddition because the barrier for rotation is higher than that for reversal
      to the reactants 1 and 2. The electrophilicity parameters E correlate moderately
      with the lowest unoccupied molecular orbital energies of the carbonyl groups,
      very poorly with Parr's electrophilicity indices, and best with the methyl anion
      affinities calculated for DMSO solution.

PMID- 29659265
TI  - Response to Comment on The Case Against Charge Transfer Interactions in Dissolved
      Organic Matter Photophysics.

PMID- 29659266
TI  - Dechlorinated Analogues of Dechlorane Plus.
AB  - Degradation products of the chlorinated additive flame retardant Dechlorane Plus
      (DP) have been discovered globally. However, the identity of many of these
      species remains unknown due to a lack of available analytical standards,
      hindering the ability to quantitatively measure the amounts of these compounds in
      the environment. In the present study, synthetic routes to possible dechlorinated
      DP derivatives were investigated in an effort to identify the environmentally
      significant degradation products. The methano-bridge chlorines of anti- and syn
      DP were selectively replaced by hydrogen atoms to give six new hydrodechlorinated
      DP analogues. The identity and absolute configuration of all of these compounds
      were confirmed by GC-MS, NMR spectroscopy, and X-ray diffraction studies. These
      compounds were observed in sediment samples from streams and rivers in relatively
      rural areas of Ontario and are thus environmentally relevant.

PMID- 29659267
TI  - Comment on The Case Against Charge Transfer Interactions in Dissolved Organic
      Matter Photophysics.

PMID- 29659268
TI  - Human Liver Microsomes Atropselectively Metabolize 2,2',3,4',6
      Pentachlorobiphenyl (PCB 91) to a 1,2-Shift Product as the Major Metabolite.
AB  - Polychlorinated biphenlys (PCBs) and their hydroxylated metabolites (OH-PCBs)
      have been implicated in neurodevelopmental disorders. Several neurotoxic PCBs,
      such as PCB 91, are chiral because they form stable rotational isomers, or
      atropisomers, that are nonsuperimposable mirror images of each other. Because
      only limited information about the metabolism of these PCBs by human cytochrome
      P450 (P450) enzymes is available, we investigated the biotransformation of PCB 91
      to OH-PCBs by human liver microsomes (HLMs). Racemic PCB 91 was incubated with
      pooled or individual donor HLMs at 37  degrees C, and levels and chiral
      signatures of PCB 91 and its metabolites were determined. Several OH-PCBs were
      formed in the order 2,2',4,4',6-pentachlorobiphenyl-3-ol (3-100; 1,2 shift
      product) > 2,2',3,4',6-pentachlorobiphenyl-5-ol (5-91) ? 2,2',3,4',6
      pentachlorobiphenyl-4-ol (4-91) ? 4,5-dihydroxy-2,2',3,4',6-pentachlorobiphenyl
      (4,5-91). Metabolite formation rates displayed interindividual variability. The
      first eluting atropisomers of PCB 91, 3-100 and 4-91, and the second eluting
      atropisomer of 5-91 were enriched in most metabolism studies. The unexpected,
      preferential formation of a 1,2-shift product and the variability of the OH-PCBs
      profiles in experiments with individual donor HLMs underline the need for further
      systematic studies of the atropselective metabolism of PCBs in humans.

PMID- 29659269
TI  - Aqueous-Processed, High-Capacity Electrodes for Membrane Capacitive Deionization.
AB  - Membrane capacitive deionization (MCDI) is a low-cost technology for
      desalination. Typically, MCDI electrodes are fabricated using a slurry of
      nanoparticles in an organic solvent along with polyvinylidene fluoride (PVDF)
      polymeric binder. Recent studies of the environmental impact of CDI have pointed
      to the organic solvents used in the fabrication of CDI electrodes as key
      contributors to the overall environmental impact of the technology. Here, we
      report a scalable, aqueous processing approach to prepare MCDI electrodes using
      water-soluble polymer poly(vinyl alcohol) (PVA) as a binder and ion-exchange
      polymer. Electrodes are prepared by depositing aqueous slurry of activated carbon
      and PVA binder followed by coating with a thin layer of PVA-based cation- or
      anion-exchange polymer. When coated with ion-exchange layers, the PVA-bound
      electrodes exhibit salt adsorption capacities up to 14.4 mg/g and charge
      efficiencies up to 86.3%, higher than typically achieved for activated carbon
      electrodes with a hydrophobic polymer binder and ion-exchange membranes (5-13
      mg/g). Furthermore, when paired with low-resistance commercial ion-exchange
      membranes, salt adsorption capacities exceed 18 mg/g. Our overall approach
      demonstrates a simple, environmentally friendly, cost-effective, and scalable
      method for the fabrication of high-capacity MCDI electrodes.

PMID- 29659270
TI  - Response to Comments on "Assessing the Risk of Engineered Nanomaterials in the
      Environment: Development and Application of the nanoFate Model".

PMID- 29659271
TI  - Structural Series in the Ternary A-Mn-As System (A = Alkali Metal): Double-Layer
      Type CsMn4As3 and RbMn4As3 and Tunnel-Type KMn4As3.
AB  - New manganese arsenides CsMn4As3, RbMn4As3, and KMn4As3 were synthesized by solid
      state reaction. They consist of edge-sharing MnAs4 tetrahedra, which are a
      building block similar to those of Fe-based superconductors. CsMn4As3 and
      RbMn4As3 adopt the KCu4S3-type structure (tetragonal P4/ mmm space group, No.
      123) with a Mn4As3 double layer, while KMn4As3 has the CaFe4As3-type structure
      (orthorhombic Pnma space group, No. 62) with a Mn4As3 tunnel framework. The
      structural change from CsMn4As3 and RbMn4As3 to KMn4As3 as well as the structural
      trend of the other ternary A-Mn-As (A = alkali metal) and AE-Mn-As (AE = alkaline
      earth metal) compounds is understood as a consequence of reduction of the
      coordination number around the A and AE sites owing to the decrease of the ionic
      radius from Cs+ to Mg2+. Electrical resistivity measurements confirm that the
      three new phases are Mott insulators with band gaps of 0.52 (CsMn4As3), 0.43
      (RbMn4As3), and 0.31 eV (KMn4As3). Magnetic and heat capacity measurements
      revealed that CsMn4As3 and RbMn4As3 are antiferromagnets without apparent phase
      transitions below 400 K, which is similar to the magnetism of LaMnAsO and
      BaMn2As2, while the existence of the ferromagnetic component was indicated in
      KMn4As3 with a magnetic transition at 179 K.

PMID- 29659272
TI  - Comment on "Assessing the Risk of Engineered Nanomaterials in the Environment:
      Development and Application of the nanoFate Model".

PMID- 29659273
TI  - Nontarget Mass Spectrometry Reveals New Perfluoroalkyl Substances in Fish from
      the Yangtze River and Tangxun Lake, China.
AB  - Nontarget high-resolution mass spectrometry (Nt-HRMS) has been proven useful for
      the identification of unknown poly- and perfluoroalkyl substances (PFASs) in
      commercial products and water, but applications to biological samples are
      limited. China is the major PFAS-manufacturing nation; thus, here, we adapted our
      Nt-HRMS methods to fish collected from the Yangtze River and Tangxun Lake to
      discover potentially bioaccumulative PFASs in aquatic organisms destined for
      human consumption. In addition to traditional PFASs, over 330 other fluorinated
      analytes belonging to 10 classes of PFASs were detected among the pooled fish
      livers, including 6 sulfonate classes, 2 amine classes, 1 carboxylate class, and
      1 N-heterocycle class. One class was detected in samples from both locations, 8
      classes were detected exclusively in Tangxun Lake fish, and 1 class was detected
      exclusively in Yangtze River fish, 10 km downstream of a fluorochemical
      manufacturing site where we first reported these substances in wastewater 3 years
      ago. Overall, 4 of the PFAS classes (>165 analytes) are reported for the first
      time here. Wider monitoring and toxicological testing should be a priority for
      understanding the health risks posed to people and wildlife exposed to these
      substances.

PMID- 29659274
TI  - Quantitative Understanding of SHAPE Mechanism from RNA Structure and Dynamics
      Analysis.
AB  - The selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) method
      probes RNA local structural and dynamic information at single nucleotide
      resolution. To gain quantitative insights into the relationship between
      nucleotide flexibility, RNA 3D structure, and SHAPE reactivity, we develop a 3D
      Structure-SHAPE Relationship model (3DSSR) to rebuild SHAPE profiles from 3D
      structures. The model starts from RNA structures and combines nucleotide
      interaction strength and conformational propensity, ligand (SHAPE reagent)
      accessibility, and base-pairing pattern through a composite function to quantify
      the correlation between SHAPE reactivity and nucleotide conformational stability.
      The 3DSSR model shows the relationship between SHAPE reactivity and RNA structure
      and energetics. Comparisons between the 3DSSR-predicted SHAPE profile and the
      experimental SHAPE data show correlation, suggesting that the extracted
      analytical function may have captured the key factors that determine the SHAPE
      reactivity profile. Furthermore, the theory offers an effective method to sieve
      RNA 3D models and exclude models that are incompatible with experimental SHAPE
      data.

PMID- 29659275
TI  - Globally Accurate Potential Energy Surface for HCS(A2A") by Extrapolation to the
      Complete Basis Set Limit.
AB  - A global potential energy surface (PES) representation of the C(3P) + SH(X 2Pi) 
      > H(2S) + CS(a 3Pi) system is developed by fitting plenty of precise energies
      obtained through the ab initio calculation with aug-cc-pV QZ and aug-cc-pV5Z
      basis sets via extrapolation to the complete basis set limit. The topographical
      characteristics of the PES are examined in detail, and it is found that they
      agree well with previous calculations available in the literature. By utilizing
      the PES of HCS(A2A"), the corresponding reaction is investigated using the quasi
      classical trajectory (QCT) method in the collision energy range of 0.08-1.0 eV.
      The minimum energy paths (MEPs) calculated on the basis of the present PES
      indicate that the C(3P) + SH(X 2Pi) -> H(2S) + CS(a 3Pi) reaction is exothermic,
      with the exothermicity ~0.204 eV. The calculation for the capture time indicates
      that the reaction is mainly governed by the indirect mechanism at the lower
      collision energy, while, for higher collision energy, the direct mechanism is in
      coexistence with the indirect mechanism, and the latter one plays a dominant
      role.

PMID- 29659276
TI  - Protocols for Requirement-Driven Protein Design in the Rosetta Modeling Program.
AB  - We have developed a set of protocols in the molecular modeling program Rosetta
      for performing requirement-driven protein design. First, the user specifies a set
      of structural features that need to be present in the designed protein. These
      requirements can be general (e.g., "create a protein with five helices"), or they
      can be very specific and require the correct placement of a set of amino acids to
      bind a ligand. Next, a large set of protein models are generated that satisfy the
      design requirements. The models are built using a method that we recently
      introduced into Rosetta, called SEWING, that rapidly assembles novel protein
      backbones by combining pieces of naturally occurring proteins. In the last step
      of the process, rotamer-based sequence optimization and backbone refinement are
      performed with Rosetta, and a variety of quality metrics are used to pick
      sequences for experimental characterization. Here we describe the input files and
      user options needed to run SEWING and perform requirement-driven design and
      provide detailed instructions for two specific applications of the process: the
      design of new structural elements at a protein-protein interface and the design
      of ligand binding sites.

PMID- 29659277
TI  - QM/MM Study of the Formation of the Dioxetanone Ring in Fireflies through a
      Superoxide Ion.
AB  - The bioluminescence emission from fireflies is an astounding tool to mark and
      view cells. However, the bioluminescent mechanism is not completely deciphered,
      limiting the comprehension of key processes. We use a theoretical approach to
      study for the first time the arrival of a dioxygen molecule inside the fireflies
      protein and one path of the formation of the dioxetanone ring, the high-energy
      intermediate precursor of the bioluminescence. To describe this reaction step, a
      joint approach combining classical molecular dynamics (MD) simulations and hybrid
      quantum mechanics/molecular mechanics (QM/MM) calculations is used. The formation
      of the dioxetanone ring has been studied for both singlet and triplet states with
      the help of MS-CASPT2 calculations. We also emphasize the role played by the
      proteinic environment in the formation of the dioxetanone ring. The results
      obtained shed some light on an important reaction step and give new insights
      concerning the bioluminescence in fireflies.

PMID- 29659278
TI  - Mechanism of Photoinduced Triplet Intermolecular Hydrogen Transfer between
      Cycloxydim and Chlorothalonil.
AB  - The possible reaction mechanisms for the experimentally observed hydrogen
      transfer between the herbicide cycloxydim (CD) and the triplet fungicide
      chlorothalonil (CT) were identified with density functional theory (DFT) and time
      dependent density function theory (TDDFT) computations. Excited energy transfer
      (EET) calculations indicate that reactants for intermolecular hydrogen transfer
      were formed via energy transfer from triplet CT to ground state CD. Three
      possible reaction pathways after EET were identified, and hydrogen transfer from
      the hydroxyl group on the cyclohexane ring of CD to CT exhibited the lowest
      energy barrier. Natural population analysis (NPA) along the reaction pathways has
      confirmed that the pathways involved either electron transfer induced proton
      transfer or coupled electron-proton transfer, leading to different potential
      energy profiles. Electrostatic potential (ESP) study substantiated the reaction
      mechanisms in different pathways. This study suggests an explanation for the
      accelerated photodegradation of CD by CT and provides a pipeline for future
      studies of photoinduced intermolecular hydrogen transfer.

PMID- 29659279
TI  - Hydration of an Acid Anhydride: The Water Complex of Acetic Sulfuric Anhydride.
AB  - The complex formed from acetic sulfuric anhydride (CH3COOSO2OH, ASA) and water
      has been observed by pulsed nozzle Fourier transform microwave spectroscopy. ASA
      was formed in situ in the supersonic jet via the reaction of SO3 and CH3COOH, and
      subsequently complexed with water using a concentric, dual injection needle that
      allows reagents to be introduced at different points along the expansion axis.
      Spectroscopic constants for the parent, fully deuterated, and CH313COOSO2OH
      species are reported. Both A and E internal rotor states have been observed and
      analyzed. The fitted internal rotation barrier of the methyl group is 219.598(21)
      cm-1 for the parent species, indicating that complexation with water lowers the
      internal rotation barrier of the methyl group by 9% relative to that of the free
      ASA. M06-2X/6-311++G(3df,3pd) calculations predict at least two distinct isomeric
      forms of ASA...H20. Spectroscopic constants for the observed species agree with
      those for the lower energy isomer in which the water inserts into the
      intramolecular hydrogen bond of the ASA monomer. CCSD(T)/CBS(D-T) calculations
      place the binding energy of this isomer at 13.3 kcal/mol below that of the
      isolated ASA and H2O monomers. The calculations further indicate that the doubly
      hydrogen bonded complex CH3COOH...H2SO4, which contains the hydrolysis products
      of ASA, lies even lower in energy, but this species was not observed in this
      study. This system represents the first stage of microsolvation of an acid
      anhydride, and the results indicate that a single water molecule does not induce
      spontaneous hydrolysis in a cold molecular cluster.

PMID- 29659280
TI  - Synthesis and Binding Properties of Monohydroxycucurbit[7]uril: A Key Derivative
      for the Functionalization of Cucurbituril Hosts.
AB  - We present a simple, direct method to prepare monohydroxylated cucurbit[7]uril
      (CB7-OH) through the direct oxidation of its precursor host, cucurbit[7]uril
      (CB7). Although the conversion takes place in low yield (14%), the isolation of
      CB7-OH from the reaction mixture is straightforward, and the unreacted CB7 can be
      easily recovered. ITC measurements with several selected guests confirmed that
      CB7-OH binds all of them in aqueous solution with similar, albeit slightly lower,
      binding affinities than those observed with the unmodified CB7 host. ESI mass
      spectrometric competition experiments are consistent with the ITC measurements. A
      variety of spectroscopic and voltammetric measurements also verify that the CB7
      OH complexes exhibit properties essentially identical to those of the CB7
      complexes. DFT computational data also confirm the similar thermodynamic
      stabilities and structures of the CB7-OH and CB7 inclusion complexes. Finally,
      the high thermodynamic stability of the CB7-OH complexes was used to improve on
      the extraction efficiency of stir bar sorptive extraction methods after suitable
      modification of the active coating with CB7-OH.

PMID- 29659281
TI  - Theoretical and Experimental Study on the Reaction of tert-Butylamine with OH
      Radicals in the Atmosphere.
AB  - The OH-initiated atmospheric degradation of tert-butylamine (tBA), (CH3)3CNH2,
      was investigated in a detailed quantum chemistry study and in laboratory
      experiments at the European Photoreactor (EUPHORE) in Spain. The reaction was
      found to mainly proceed via hydrogen abstraction from the amino group, which in
      the presence of nitrogen oxides (NO x), generates tert-butylnitramine,
      (CH3)3CNHNO2, and acetone as the main reaction products. Acetone is formed via
      the reaction of tert-butylnitrosamine, (CH3)3CNHNO, and/or its isomer tert
      butylhydroxydiazene, (CH3)3CN?NOH, with OH radicals, which yield nitrous oxide
      (N2O) and the (CH3)3C radical. The latter is converted to acetone and
      formaldehyde. Minor predicted and observed reaction products include
      formaldehyde, 2-methylpropene, acetamide and propan-2-imine. The reaction in the
      EUPHORE chamber was accompanied by strong particle formation which was induced by
      an acid-base reaction between photochemically formed nitric acid and the reagent
      amine. The tert-butylaminium nitrate salt was found to be of low volatility, with
      a vapor pressure of 5.1 * 10-6 Pa at 298 K. The rate of reaction between tert
      butylamine and OH radicals was measured to be 8.4 (+/-1.7) * 10-12 cm3 molecule-1
      s-1 at 305 +/- 2 K and 1015 +/- 1 hPa.

PMID- 29659282
TI  - Quest for Insight into Ultrashort C-H...pi Proximities in Molecular "Iron
      Maidens".
AB  - Molecular iron maidens are a strained type of cyclophane in which a methine
      hydrogen, by the action of the bridges, is placed closer to the center of an
      aromatic ring. Such constrained molecular frameworks are in fact a noteworthy
      synthetic challenge. The present study provides a comprehensible theoretical
      analysis that elucidates unique structural and energetic aspects of this class of
      molecules, evaluating, in the light of quantum chemistry, both the influence of
      the aromatic moiety, from pi-basic to pi-acid, and the nature of the heteroatoms
      located at the bridges. Our results not only propose the shortest intramolecular
      centered C-H...pi distance to date, which is supported by calculated 1H chemical
      shifts, but also shed light on the main factors that rationalize and justify such
      proximity. QTAIM, NBO, and NCI analyses allow us prematurely to conclude that the
      ultrashort C-H...pi distance is sustained by an interplay between a large
      stabilizing electrostatic component with a non-negligible covalent character.
      However, the energetics involving such strained molecular scaffolds, addressed by
      means of isodesmic reactions, revealed that the C-H...pi proximity is modulated
      mainly by the capacity of the bridges to support the strain imposed by the whole
      structure, hence compressing the C-H bond against the pi-system.

PMID- 29659283
TI  - Submonomer Strategy toward Divergent Solid-Phase Synthesis of alpha-ABpeptoids.
AB  - A novel submonomer solid-phase synthetic method for alpha-ABpeptoid oligomers is
      reported. Iterative submonomer coupling and Fukuyama-Mitsunobu alkylation enable
      facile, divergent synthesis of alpha-ABpeptoid oligomers substituted with
      chemically diverse side chains in excellent yields.

PMID- 29659284
TI  - Accessing the Vibrational Signatures of Amino Acid Ions Embedded in Water
      Clusters.
AB  - We present an infrared predissociation (IRPD) study of microsolvated GlyH+(H2O) n
      and GlyH+(D2O) n clusters, formed inside of a cryogenic ion trap via condensation
      of H2O or D2O onto the protonated glycine ions. The resulting IRPD spectra,
      showing characteristic O-H and O-D stretches, indicate that H/D exchange
      reactions are quenched when the ion trap is held at 80 K, minimizing the presence
      of isotopomers. Comparisons of GlyH+(H2O) n and GlyH+(D2O) n spectra clearly
      highlight and distinguish the vibrational signatures of the water solvent
      molecules from those of the core GlyH+ ion, allowing for quick assessment of
      solvation structures. Without the aid of calculations, we can already infer
      solvation motifs and the presence of multiple conformations. The use of a
      cryogenic ion trap to cluster solvent molecules around ions of interest and
      control H/D exchange reactions is broadly applicable and should be extendable to
      studies of more complex peptidic ions in large solvated clusters.

PMID- 29659285
TI  - Tuning Confinement in Colloidal Silicon Nanocrystals with Saturated Surface
      Ligands.
AB  - The optical properties of silicon nanocrystals (Si NCs) are a subject of intense
      study and continued debate. In particular, Si NC photoluminescence (PL)
      properties are known to depend strongly on the surface chemistry, resulting in
      electron-hole recombination pathways derived from the Si NC band-edge, surface
      state defects, or combined NC-conjugated ligand hybrid states. In this Letter, we
      perform a comparison of three different saturated surface functional groups
      alkyls, amides, and alkoxides-on nonthermal plasma-synthesized Si NCs. We find a
      systematic and size-dependent high-energy (blue) shift in the PL spectrum of Si
      NCs with amide and alkoxy functionalization relative to alkyl. Time-resolved
      photoluminescence and transient absorption spectroscopies reveal no change in the
      excited-state dynamics between Si NCs functionalized with alkyl, amide, or
      alkoxide ligands, showing for the first time that saturated ligands-not only
      surface-derived charge-transfer states or hybridization between NC and low-lying
      ligand orbitals-are responsible for tuning the Si NC optical properties. To
      explain these PL shifts we propose that the atom bound to the Si NC surface
      strongly interacts with the Si NC electronic wave function and modulates the Si
      NC quantum confinement. These results reveal a potentially broadly applicable
      correlation between the optoelectronic properties of Si NCs and related quantum
      confined structures based on the interaction between NC surfaces and the ligand
      binding group.

PMID- 29659286
TI  - Biomimetic Syntheses of Callistrilones A-E via an Oxidative [3 + 2]
      Cycloaddition.
AB  - Concise total syntheses of callistrilones A-E have been achieved from 7 and
      commercially available alpha-phellandrene (8). The synthetic strategy, which was
      primarily inspired by the biogenetic hypothesis, was enabled by an oxidative [3 +
      2] cycloaddition followed by a Michael addition and an intramolecular
      nucleophilic addition to construct the target molecules. Moreover, viminalin I
      was also synthesized, and its absolute configuration was unambiguously confirmed.

PMID- 29659287
TI  - Polymeric Precipitation Inhibitors Promote Fenofibrate Supersaturation and
      Enhance Drug Absorption from a Type IV Lipid-Based Formulation.
AB  - The ability of lipid-based formulations (LBFs) to increase the solubilization,
      and prolong the supersaturation, of poorly water-soluble drugs (PWSDs) in the
      gastrointestinal (GI) fluids has generated significant interest in the past
      decade. One mechanism to enhance the utility of LBFs is to prolong
      supersaturation via the addition of polymers that inhibit drug precipitation
      (polymeric precipitation inhibitors or PPIs) to the formulation. In this work, we
      have evaluated the performance of a range of PPIs and have identified PPIs that
      are sufficiently soluble in LBF to allow the construction of single phase
      formulations. An in vitro model was first employed to assess drug (fenofibrate)
      solubilization and supersaturation on LBF dispersion and digestion. An in vitro
      in situ model was subsequently employed to simultaneously evaluate the impact of
      PPI enhanced drug supersaturation on drug absorption in rats. The stabilizing
      effect of the polymers was polymer specific and most pronounced at higher drug
      loads. Polymers that were soluble in LBF allowed simple processing as single
      phase formulations, while formulations containing more hydrophilic polymers
      required polymer suspension in the formulation. The lipid-soluble polymers
      Eudragit (EU) RL100 and poly(propylene glycol) bis(2-aminopropyl ether) (PPGAE)
      and the water-soluble polymer hydroxypropylmethyl cellulose (HPMC) E4M were
      identified as the most effective PPIs in delaying fenofibrate precipitation in
      vitro. An in vitro model of lipid digestion was subsequently coupled directly to
      an in situ single pass intestinal perfusion assay to evaluate the influence of
      PPIs on fenofibrate absorption from LBFs in vivo. This coupled model allowed for
      real-time evaluation of the impact of supersaturation stabilization on absorptive
      drug flux and provided better discrimination between the different PPIs and
      formulations. In the presence of the in situ absorption sink, increased
      fenofibrate supersaturation resulted in increased drug exposure, and a good
      correlation was found between the degree of in vitro supersaturation and in vivo
      drug exposure. An improved in vitro-in vivo correlation was apparent when
      comparing the same formulation under different supersaturation conditions. These
      observations directly exemplify the potential utility of PPIs in promoting drug
      absorption from LBF, via stabilization of supersaturation, and further confirm
      that relatively brief periods of supersaturation may be sufficient to promote
      drug absorption, at least for highly permeable drugs such as fenofibrate.

PMID- 29659288
TI  - Redox-Neutral Atom-Economic Pd(0)-Catalyzed Dearomatization of beta-Naphthols
      with Alkynes toward Naphthalenones.
AB  - A dearomative coupling of beta-naphthols with alkynes via Pd hydride catalysis
      has been developed. This redox-neutral strategy provides a straightforward
      platform to access diverse naphthalenones bearing congested quarternary
      stereocenters with excellent atom and step economy since no leaving groups are
      needed to preinstall on the allylic reagents. The overall utility of this
      protocol is exemplified by broad functional group compatibility and gram-scale
      capacity.

PMID- 29659289
TI  - Copper-Catalyzed Synthesis of Polysubstituted Pyrroles through [3+1+1]
      Cycloaddition Reaction of Nitrones and Isocyanides.
AB  - An efficient, copper-catalyzed [3+1+1] cycloaddition reaction was developed for
      the expedient synthesis of pharmacologically interesting polysubstituted pyrroles
      from easily available nitrones and alpha-acidic isocyanides. The given approach
      features a new mode of cycloaddition between nitrones and isocyanides with wide
      substrate scope, good functional group tolerance, and operational simplicity. The
      operando infrared spectroscopy was used for the characterization of reaction
      intermediates.

PMID- 29659290
TI  - Controlling Self-Assembly and Topology at Micro-Nano Length Scales Using a
      Contact-Free Mixed Nanocolloid Droplet Architecture.
AB  - Spatially varying the ordering of colloids of multiple sizes at micro-nano scales
      finds application in different industrial processes including manufacturing of
      photonic crystals. In this work, we showcase a unique physics-based architecture
      through which we have been able to control the morphology of the precipitates
      evolving out of the drying of a contact-free droplet at micro to nano length
      scales. We show that by varying the relative concentration of the larger sized
      colloids, one can modulate evaporation, subsequent particle transport, and
      particle ordering at the droplet interface, thereby controlling the rates of
      certain instabilities like buckling. In this way, we have produced evaporation
      induced self-assembly structures (devoid of any substrate effect) with striking
      topological and surface features. Furthermore, we proved that these instabilities
      can be further tuned using a measured amount of external heating through the
      alteration of the evaporation rates. Notwithstanding, we also quantified that the
      ordering of the mixed colloids varies, in a spatial sense, across the droplet
      surface, exhibiting unique patterns, porosity, and lattice arrangements, all at
      the nanoscale. The results assure that the fine-tuning of the macroscale
      parameters like heating rate and particle loading can be used to fine-tune the
      micro-nanoscale features in a droplet-based high-throughput bottom-up framework.

PMID- 29659291
TI  - Synthesis, Characterization, and Rapid Cycloadditions of 5-Nitro-1,2,3-triazine.
AB  - The synthesis, characterization, and a study of the cycloaddition reactions of 5
      nitro-1,2,3-triazine (3) are reported. The electron-deficient nature of 3 permits
      rapid cycloaddition with a variety of electron-rich dienophiles, including
      amidines, enamines, enol ethers, ynamines, and ketene acetals in high to moderate
      yields. 1H NMR studies of a representative cycloaddition reaction between 3 and
      an amidine revealed a remarkable reaction rate and efficiency (1 mM, <60 s,
      CD3CN, 23  degrees C, >95%).

PMID- 29659292
TI  - Cu-Catalyzed Aerobic Oxidative Sulfuration/Annulation Approach to Thiazoles via
      Multiple Csp3-H Bond Cleavage.
AB  - A novel and practical Cu-catalyzed aerobic oxidative synthesis of thiazoles was
      developed. This chemistry for the first time achieved thiazole construction from
      simple aldehydes, amines, and element sulfur through multiple Csp3-H bond
      cleavage processes. Molecular oxygen was used as a green oxidant in this
      oxidative protocol. The substrate scope is broad with the tolerance of aliphatic
      amines. The mechanistic study might promote the reaction design for a new
      sulfuration/annulation reaction with readily available element sulfur.

PMID- 29659293
TI  - Solid-State Characterization and Relative Formation Enthalpies To Evaluate
      Stability of Cocrystals of an Antidiabetic Drug.
AB  - The current study integrates formation enthalpy and traditional slurry
      experiments to quickly assess the physical stability of cocrystal drug substance
      candidates for their potential to support drug development. Cocrystals of an
      antidiabetic drug (GKA) with nicotinamide (NMA), vanillic acid (VLA), and ethyl
      vanillin (EVL) were prepared and characterized by powder X-ray diffractometry
      (PXRD), spectroscopic, and thermal techniques. The formation enthalpies of the
      cocrystals, and their physical mixtures (GKA + coformer) were measured by the
      differential scanning calorimetry (DSC) method reported by Zhang et al. [ Cryst.
      Growth Des. 2012 , 12 ( 8 ), 4090 - 4097 ]. The experimentally measured
      differences in the relative formation enthalpies obtained by integrating the heat
      flow of each cocrystal against the respective physical mixture were correlated to
      the physical stability of the cocrystals in the solid state. The relative
      formation enthalpies of all of the cocrystals studied suggest that the cocrystals
      are not physically stable at room temperature versus their physical mixtures. To
      further address relative stability, the cocrystals were slurried in 30% v/v
      aqueous ethanol, and it was observed that all of the cocrystals revert to GKA
      within 48 h at room temperature. The slurry experiments are consistent with the
      relative instability of the cocrystals with respect to their physical mixtures
      suggested by the DSC results.

PMID- 29659294
TI  - Palladium-Catalyzed Direct C-H Arylation of 3-(Methylsulfinyl)thiophenes.
AB  - A palladium-catalyzed direct arylation of (3-thiophene)S(O)Me derivatives has
      been developed. This protocol is effective for the selective synthesis of 2
      arylated and 2,5-diarylated sulfinylthiophene derivatives with as low as 0.5 mol
      % catalyst loading. Various functional groups are well tolerated. A method to
      install two different aryl groups on 3-(methylsulfinyl)thiophenes is also
      introduced.

PMID- 29659295
TI  - Total Synthesis of Selligueain A, a Sweet Flavan Trimer.
AB  - The first total synthesis of selligueain A (4), a plant-derived sweet polyphenol,
      has been achieved. The key step was the de novo synthetic approach to the
      selectively protected epiafzelechin unit 10, which was divergently converted to
      three flavan units 7, 8, and 9. These components were combined by an orthogonal
      activation and annulation method, enabling assembly of the characteristic
      trimeric structure with single and double interflavan linkages.

PMID- 29659297
TI  - Erratum.

PMID- 29659296
TI  - Mental health knowledge and training needs among direct care workers: a mixed
      methods study.
AB  - OBJECTIVES: Direct care providers (DCWs) spend the most time with clients in the
      home, and as such, play an integral role in identifying mental health problems.
      However, DCWs receive little preparation in mental health and there is little
      research regarding their role in the mental health care of clients. The purpose
      of this study was to explore DCWs' knowledge, attitudes, and experiences of
      caring for clients with mental health problems from the perspectives of DCWs and
      key administrators (KAs). METHOD: Mixed method design. Structured interviews were
      conducted with DCWs. Focus groups were conducted with KAs. RESULTS: Twenty-nine
      DCWs and 12 KAs took part in the study. Loneliness and memory problems in clients
      were the most prevalent challenges identified by DCWs. DCWs' self-reported mental
      health knowledge was mid to high across all domains, although they had many
      misconceptions about mental health and aging. Helpful strategies in working with
      clients included communication skills, rapport-building, behavioral, cognitive,
      emotion-regulation, and making use of external resources. KAs noted individual
      differences in DCWs' mental health knowledge and indicated that mental health
      issues were often viewed by DCWs as dispositional problems or a normal part of
      aging. KAs viewed DCWs' greatest challenges as personalizing difficult client
      behaviors, lack of knowledge about how to manage specific behaviors, and
      difficulties managing their own emotions towards clients. CONCLUSION: Data from
      this study suggest important areas for DCW development. However, system issues
      that affect DCWs such as workload, resources, mental health stigma, and diverse
      client populations should be addressed concurrently.

PMID- 29659298
TI  - Agreement Between Visual Assessment and 2-Dimensional Analysis During Jump
      Landing Among Healthy Female Athletes.
AB  - CONTEXT:   Altered movement patterns, including increased frontal-plane knee
      movement and decreased sagittal-plane hip and knee movement, have been associated
      with several knee disorders. Nevertheless, the ability of clinicians to visually
      detect such altered movement patterns during high-speed athletic tasks is
      relatively unknown. OBJECTIVE:   To explore the association between visual
      assessment and 2-dimensional (2D) analysis of frontal-plane knee movement and
      sagittal-plane hip and knee movement during a jump-landing task among healthy
      female athletes. DESIGN:   Cross-sectional study. SETTING:   Gymnasiums of
      participating volleyball teams. PATIENTS OR OTHER PARTICIPANTS:   A total of 39
      healthy female volleyball players (age = 21.0 +/- 5.2 years, height = 172.0 +/-
      8.6 cm, mass = 64.2 +/- 7.2 kg) from Divisions I and II of the Israeli Volleyball
      Association. MAIN OUTCOME MEASURE(S):   Frontal-plane knee movement and sagittal
      plane hip and knee movement during jump landing were visually rated as good,
      moderate, or poor based on previously established criteria. Frontal-plane knee
      excursion and sagittal-plane hip and knee excursions were measured using free
      motion-analysis software and compared among athletes with different visual
      ratings of the corresponding movements. RESULTS:   Participants with different
      visual ratings of frontal-plane knee movement displayed differences in 2D frontal
      plane knee excursion ( P < .01), whereas participants with different visual
      ratings of sagittal-plane hip and knee movement displayed differences in 2D
      sagittal-plane hip and knee excursions ( P < .01). CONCLUSIONS:   Visual ratings
      of frontal-plane knee movement and sagittal-plane hip and knee movement were
      associated with differences in the corresponding 2D hip and knee excursions.
      Visual rating of these movements may serve as an initial screening tool for
      detecting altered movement patterns during jump landings.

PMID- 29659299
TI  - Low 1-Year Return-to-Sport Rate After Anterior Cruciate Ligament Reconstruction
      Regardless of Patient and Surgical Factors: A Prospective Cohort Study of 272
      Patients.
AB  - BACKGROUND: There is insufficient knowledge about the way that concomitant
      injuries affect the short-term likelihood of a return to a knee-strenuous sport
      after anterior cruciate ligament (ACL) reconstruction. Hypotheses/Purpose: The
      purpose was to study whether patient characteristics, concomitant injuries, and
      graft choice at primary ACL reconstruction can predict return to sport (RTS) 1
      year after surgery. The hypotheses were that younger age at the time of ACL
      reconstruction would positively affect RTS, while the presence of concomitant
      injuries would negatively affect RTS 1 year after surgery. STUDY DESIGN: Case
      control study; Level of evidence, 3. METHODS: Data were extracted from a
      rehabilitation-specific register and the Swedish National Knee Ligament Register.
      Twelve months after surgery, all patients were evaluated for RTS via the Tegner
      Activity Scale. The primary outcome was a return to knee-strenuous sport, defined
      as a Tegner Activity Scale >=6. Univariable and multivariable logistic regression
      analyses were performed with patient characteristics, concomitant knee injuries,
      and graft choice as independent variables. RESULTS: A total of 272 patients (51%
      female) with a mean +/- SD age of 25.0 +/- 9.2 years were included. In the
      multivariable analysis, a favorable odds ratio (OR) for returning to sport was
      found for patients of male sex (OR, 2.58; 95% CI, 1.43-4.65; P = .0016), younger
      age at the time of ACL reconstruction (OR, 2.32; 95% CI, 1.59-3.33; P < .0001), a
      higher preinjury score on the Tegner Activity Scale (OR, 1.45; 95% CI, 1.13-1.87;
      P = .0038), and an absence of injury to the meniscus (OR, 1.92; 95% CI, 1.10
      3.36; P = .023) and medial collateral ligament (OR, 7.61; 95% CI, 1.42-40.87; P =
      .018). In addition, the absence of cartilage injury was favorable in terms of RTS
      in the univariable analysis (OR, 2.48; 95% CI, 1.40-4.39; P = .0018). CONCLUSION:
      Positive predictors of a return to knee-strenuous sport 1 year after ACL
      reconstruction were male sex, younger age, a high preinjury level of physical
      activity, and the absence of concomitant injuries to the medial collateral
      ligament and meniscus.

PMID- 29659300
TI  - Otic drug delivery systems: formulation principles and recent developments.
AB  - Disorders of the ear severely impact the quality of life of millions of people,
      but the treatment of these disorders is an ongoing, but often overlooked
      challenge particularly in terms of formulation design and product development.
      The prevalence of ear disorders has spurred significant efforts to develop new
      therapeutic agents, but perhaps less innovation has been applied to new drug
      delivery systems to improve the efficacy of ear disease treatments. This review
      provides a brief overview of physiology, major diseases, and current therapies
      used via the otic route of administration. The primary focuses are on the various
      administration routes and their formulation principles. The article also presents
      recent advances in otic drug deliveries as well as potential limitations. Otic
      drug delivery technology will likely evolve in the next decade and more efficient
      or specific treatments for ear disease will arise from the development of less
      invasive drug delivery methods, safe and highly controlled drug delivery systems,
      and biotechnology targeting therapies.

PMID- 29659301
TI  - Cross-cultural validation of a Brazilian version of the adapted manual wheelchair
      circuit (AMWC-Brazil).
AB  - PURPOSE: To translate, culturally adapt and validate the Adapted Manual
      Wheelchair Circuit (AMWC) into Brazilian-Portuguese. DESIGN: Cross-sectional
      study. METHODS: Sixty-six men (median age of 30.5 years [percentiles 25 and 75:
      24.0; 38.3 years]) with traumatic spinal cord injury were consecutively enrolled
      and divided into two groups: tetraplegia (TP) and paraplegia (PP). The
      participants performed the AMWC-Brazil and were evaluated by the Spinal Cord
      Injury Measure version III (SCIM-III). Translation, translation synthesis, back
      translation, committee review and construct validity were adopted for the cross
      cultural adaptation. Construct validity was performed by testing whether the test
      scores were significantly correlated (Spearman's correlation coefficient) to the
      subjects' injury level, age, time since injury, body mass index (BMI) and SCIM
      III scale. RESULTS: All the AMWC-Brazil's outcomes were significantly correlated
      with SCIM-III total score and subscales (P <= 0.01). However, when the analyses
      were stratified over injury level, only the TP showed a high correlation between
      the AMWC-Brazil's outcomes and the SCIM-III. For construct validity, 4 of 5
      hypotheses were confirmed. Only BMI was not a significant predictor of the AMWC
      Brazil outcomes. CONCLUSION: The AMWC was successfully translated to the
      Brazilian-Portuguese (AMWC-Brazil) and presented high and satisfactory construct
      validity.

PMID- 29659302
TI  - Substantial contribution and accountability: best authorship practices for
      medical writers in biomedical publications.
AB  - OBJECTIVE: To provide clarity on the professional medical writer as author or
      contributor by examining what "a substantial contribution" and "accountability"
      mean with respect to authorship in a biomedical publication. These terms relate
      to criteria 1 and 4 of the International Committee of Medical Journal Editors
      (ICMJE) authorship guidelines. METHODS: We reviewed the ICMJE and Good
      Publication Practice authorship guidelines, which recommend that individuals not
      meeting all four authorship criteria should be acknowledged as contributors. We
      also surveyed and assessed selected journals for published guidance on authorship
      versus contributorship. RESULTS: We found that journals often vary in their
      authorship guidelines for medical writers. Notwithstanding, and to assist in
      determining the contribution made by the medical writer, we have expanded on
      current guidelines to develop recommendations for important intellectual
      contribution to the design of the work (developing the protocol, choosing
      endpoints) or the interpretation of data for the work (developing the discussion,
      interpreting new statistical output), which should result in inclusion of the
      medical writer as an author, as well as when accountability is relevant. If the
      medical writer does not qualify as an author, then their inclusion in the
      acknowledgements section is appropriate. CONCLUSIONS: Authors and contributors
      have a responsibility to create a publication that is accurate and true to the
      study results, but only authors must provide a substantial contribution and are
      accountable for that contribution. Contributions made by authors and non-author
      contributors should be fully described in the publication, to enable the reader
      to assess credit and responsibility.

PMID- 29659303
TI  - Activity training on the ground in children with cerebral palsy: Systematic
      review and meta-analysis.
AB  - PURPOSE: To systematically review the evidence about whether activity training on
      the ground is effective on activity or participation in children with cerebral
      palsy. METHODS: Randomized controlled trials (RCTs) were searched in databases
      using relevant keywords. RCTs were included with children (<=18 years) with
      cerebral palsy who received activity training on the ground only or activity
      training on the ground combined with another type of physiotherapy. Outcome
      measures classified as measures of activity or participation according to the
      International Classification of Functioning, Disability, and Health were
      analyzed. RESULTS: Nine RCTs (257 participants) were included in this review.
      Individual studies resulted in conflicting results when activity training on the
      ground was compared to no intervention. Based on meta-analysis, activity training
      on the ground was not more effective than no intervention (standardized mean
      difference [SMD]: 0.18; confidence interval [CI]: -1.49 to 1.86) or other
      therapies (SMD: -0.09; CI: -0.86 to 0.69) (I2 > 75%) on improving activity or
      participation. Results from a single study demonstrated that activity training on
      the ground combined with other physiotherapy intervention was not more effective
      than no intervention (SMD: -0.18 CI: -0.89 to 0.54). CONCLUSIONS: The available
      evidence shows little effect of activity training on the ground on activity or
      participation in children with cerebral palsy, suggesting that rigorous trials
      with larger samples and larger "dosage" of activity training on the ground are
      needed in the future.

PMID- 29659304
TI  - Diet-induced obesity reduces core body temperature across the estrous cycle and
      pregnancy in the rat.
AB  - Obesity during pregnancy causes adverse maternal and fetal health outcomes and
      programs offspring for adult-onset diseases, including cardiovascular disease.
      Obesity also disrupts core body temperature (Tc) regulation in nonpregnant
      rodents; however, it is unknown whether obesity alters normal maternal Tc
      adaptations to pregnancy. Since Tc is influenced by the circadian system, and
      both obesity and pregnancy alter circadian biology, it was hypothesized that
      obesity disrupts the normal rhythmic patterns of Tc before and during gestation.
      Obesity was induced by cafeteria (CAF) feeding in female Wistar rats for 8 weeks
      prior to and during gestation, whereas control (CON) animals had free access to
      chow. Intraperitoneal temperature loggers measured daily Tc profiles throughout
      the study, while maternal body composition and leptin levels were assessed near
      term. Daily temperature profiles were examined for rhythmic features (mesor,
      amplitude and acrophase) by cosine regression analysis. CAF animals exhibited
      increased fat mass (93%) and associated hyperleptinemia (3.2-fold increase)
      compared to CON animals. CAF consumption reduced the average Tc (by up to 0.29
      degrees C) across the estrous cycle and most of pregnancy; however, Tc for CAF
      and CON animals converged toward the end of gestation. Obesity reduced the
      amplitude of Tc rhythms at estrus and proestrus and on day 8 of pregnancy, but
      increased the amplitude at day 20 of pregnancy. Photoperiod analysis revealed
      that obesity reduced Tc exclusively in the light period during pre-pregnancy but
      only during the dark period in late gestation. In conclusion, obesity alters
      rhythmic Tc profiles and reduces the magnitude of the Tc decline late in rat
      gestation, which may have implications for maternal health and fetal development.

PMID- 29659305
TI  - Exposure to radiation from single or combined radio frequencies provokes
      macrophage dysfunction in the RAW 264.7 cell line.
AB  - PURPOSE: The aim of this study was to determine whether exposure to radiation
      from single or multiple radio-frequency (RF) signals at 900 and 2450 MHz would
      induce effects in the RAW 264.7 cell line. MATERIALS AND METHODS: Cell cultures
      were exposed to single or combined RF for 4, 24, 48, or 72 h in a GTEM
      electromagnetic test chamber. At the end of the radiation exposure time,
      viability and cell growth were analyzed by flow cytometry, nitric oxide (NO)
      production was measured by colorimetry, the expression of HSP70 and TNF-alpha was
      ascertained by qPCR, and the phagocytic activity was observed by microscopy.
      RESULTS: NO production increased after 48 h exposure at 2450 MHz, compared with
      controls. The group subjected to the combined interaction of two RFs showed an
      increase of HSP70 after 48 h exposure and a significant increase of NO and TNF
      alpha after 72 h. The phagocytic activity of macrophages decreased in all groups
      as exposure time increased. CONCLUSIONS: Our results indicated a decrease in
      phagocytic activity and an increase in inflammatory, cytoprotective, and
      cytotoxic responses in macrophages after continuous and combined exposure of
      multiple RF signals. Multiple RF interact in everyday life, the immune response
      in humans is unknown.

PMID- 29659306
TI  - Physical activity levels and self-determined motivation among future healthcare
      professionals: Utility of the Behavioral Regulation in Exercise Questionnaire
      (BREQ-2).
AB  - BACKGROUND: Healthcare professionals (HCPs) who are physically active are
      regarded as more likely to act as credible physical activity (PA) role models and
      promote healthy lifestyles. This study explores PA levels and underlying
      motivations, within and between HCP students, first testing the validity and
      reliability of the Behavioral Regulation in Exercise Questionnaire (BREQ-2).
      METHODS: The International Physical Activity Questionnaire (IPAQ) and BREQ-2 were
      administered to 296 HCP university students (physiotherapy n = 47, medicine n =
      105, nursing n = 121, radiography n = 23). Data were summarized using descriptive
      statistics. Mann Whitney and Kruskal Wallis tests compared scores between
      subgroups. Confirmatory factor analysis and internal consistency testing of the
      BREQ-2 was also undertaken. RESULTS: Fifty-six percent (n = 166) of respondents
      were moderately active, 40% (n = 118) highly active and 4% (n = 12) inactive.
      Participants' responses indicated mainly self-determined motivation for exercise.
      Significantly different Relative Autonomy Index (RAI) (p <= 0.001), identified (p
      <= 0.001) and intrinsic (p <= 0.001) motivation subscale scores were noted
      between HCP groups and among low, moderate and high-level PA groups. CONCLUSIONS:
      This HCP cohort were found to be active and intrinsically motivated to exercise.
      The BREQ-2 was shown to be a valid and reliable tool with strong subscale
      internal consistency.

PMID- 29659307
TI  - Recent advances in ultrasound-triggered therapy.
AB  - As a non-invasive and real-time diagnostic technique, ultrasound has provided a
      novel strategy for targeted treatment. With the rapid development of ultrasonic
      technique and ultrasound contrast agents (UCAs), spatiotemporally controllable
      application of ultrasound with or without UCAs makes it possible for site
      specific delivery of therapeutic agents and targeted modulation with minimal side
      effects, which indicated a promising therapy in clinical use. This review will
      describe the main mechanism of targeted therapy induced by ultrasound briefly,
      then focus on the current application of ultrasound mediated targeted therapy in
      various fields including tumour, cardiovascular disease, central nervous system,
      skeletal muscle system diseases and stem cells therapy. In addition, ongoing
      challenges of ultrasound-mediated targeted therapy for further research and its
      clinical use are reviewed.

PMID- 29659308
TI  - The evaluation of non-use of the upper limb in chronic hemiparesis is influenced
      by the level of motor impairment and difficulty of the activities-proposal of a
      new version of the Motor Activity Log.
AB  - This study aims to evaluate the influence of the degree of difficulty of the
      activities in Motor Activity Log (MAL) scores for patients with mild, moderate,
      and severe hemiparesis, and to estimate the correlation between motor impairment
      levels of hemiparesis and MAL scores in post-stroke patients. Sixty-six patients
      with chronic hemiparesis (49 with mild-moderate hemiparesis, and 17 with severe
      hemiparesis) were evaluated by the Fugl-Meyer upper-limb section and versions of
      MAL for different degrees of motor impairment. The Rasch model was used to
      analyze the level of difficulty of the activities of the different versions of
      MAL. The Spearman's correlation tested the relationship between the Fugl-Meyer
      Assessment upper-limb section and MAL. The MAL version, developed to evaluate
      patients with severe hemiparesis, does not contain the easier activities as
      employed by the Rasch analysis. There was positive correlation between the Fugl
      Meyer Assessment upper-limb section scores and Amount of Use of the three
      versions of the MAL (r = 0.76, 0.78, and 0.77). The difficulty of the activities
      seems to influence the quantity and quality of use of the affected upper limb in
      individuals with chronic hemiparesis. A new version of MAL is proposed for
      individuals with severe motor impairment.

PMID- 29659309
TI  - Peak expiratory flow in obese subjects in different positions.
AB  - OBJECTIVE: To analyze the peak expiratory flow (PEF) in obese subjects in
      standing (ST), seated (SE), supine (SU), prone (PR), and right and left lateral
      decubitus (RL and LL) positions. METHODS: 36 obese volunteers, aged between 18
      and 54 years, and nonsmokers, were evaluated by anthropometric data; spirometry;
      international physical activity questionnaire (IPAQ); and PEF in ST, SE, SU, PR,
      RL, and LL positions, randomly. RESULTS: The mean age was 27.3 +/- 7.4 years and
      BMI of 38.7 +/- 3.2 kg/m2; IPAQ results: active (50%), irregularly active (25%),
      very active (16.7%), and sedentary (08.3%); spirometry results: FVC = 100.33%,
      FEV1 = 92.83%, FEV1/FVC ratio = 0.95, FEF25-75% = 85.55%. The PEF (L/min) were
      within the normal range and there was no difference between the ST and SE (428.6
      +/- 100.9 and 430.0 +/- 100.1). Comparing ST and SE to the other positions, in
      absolute and percent of predicted values (L/min and %), there was a decrease in
      the SU (85.4 +/- 14.9), PR (401.1 +/- 92.4 and 84.1 +/- 14.4), RL (398.6 +/- 94.7
      and 83.3 +/- 14.9) (p < 0.05), and there was no difference to SU (409.4 +/-
      102.8) and LL (410.3 +/- 93.9 and 85.8 +/- 14.5). CONCLUSION: The PEF of healthy
      obese are similar in the standing and seated positions. The PEF decreases in the
      lying positions, except for the LL, that could be used as an alternative for
      measurements.

PMID- 29659310
TI  - Effect of feeding broccoli floret residues on leghorn layer performance and egg
      quality and nutrient digestibility.
AB  - 1. A study was conducted to determine the effects of dried broccoli floret (DBF)
      on egg production parameters, egg quality and apparent nutrient digestibility of
      laying hens. It was hypothesised that feeding DBF can improve egg quality without
      adversely affecting layer performance.2. Seventy-two White Leghorn layers aged 62
      weeks were randomly allotted to 4 dietary treatments (6 cage replicates with 3
      hens each) and fed diets containing 0, 40, 80 and 120 g/kg DBF in feed for 56
      d.3. Inclusion of DBF had no effect on feed intake, egg production, feed
      conversion ratio or egg components. However, egg weight increased (linear effect,
      P < 0.05) as the level of DBF in the diet increased. Egg breakage strength,
      eggshell strength and Haugh unit were not influenced by dietary treatments. Egg
      yolk colour (quadratic effect, P = 0.002) and alpha-tocopherol concentration
      (quadratic effect, P < 0.0001) improved as a result of DBF inclusion. Egg yolk
      cholesterol concentration was not altered by DBF inclusion. Apparent total tract
      nutrient (dry matter, organic matter and crude protein) digestibility
      coefficients decreased (linear effect, P < 0.05) as the level of DBF increased.4.
      Feeding DBF to layers up to 120 g/kg of the diet had no negative effects on feed
      intake, egg production and feed efficiency and improved egg yolk colour and alpha
      tocopherol concentration. However, total tract nutrient digestibility
      coefficients were negatively decreased as a result of DBF inclusion.

PMID- 29659311
TI  - A knowledge translation intervention designed using audit and feedback and the
      Theoretical Domains Framework for physical therapists working in inpatient
      rehabilitation: A case report.
AB  - BACKGROUND AND PURPOSE: Little is known about the process of engaging key
      stakeholders to select and design a knowledge translation (KT) intervention to
      increase the use of an outcome measure using audit and feedback. The purpose of
      this case report was to describe the development of a KT intervention designed
      with organizational support to increase physical therapists' (PTs) use of a
      selected outcome measure in an inpatient sub-acute rehabilitation hospital. CASE
      DESCRIPTION: Eleven PTs who worked at a sub-acute rehabilitation hospital
      participated. After determining organizational support, a mixed methods barrier
      assessment including a chart audit, questionnaire, and a focus group with audit
      and feedback was used to select an outcome measure and design a locally tailored
      intervention. The intervention was mapped using the Theoretical Domains Framework
      (TDF). One investigator acted as knowledge broker and co-designed the
      intervention with clinician and supervisor support. OUTCOMES: The 4-m walk test
      was selected through a group discussion facilitated by the knowledge broker.
      Support from the facility and input from the key stakeholders guided the design
      of a tailored KT intervention to increase use of gait speed. The intervention
      design included an interactive educational meeting, with documentation and
      environmental changes. DISCUSSION: Input from the clinicians on the educational
      meeting, documentation changes and placement of tracks, and support from the
      supervisor were used to design and locally adapt a KT intervention to change
      assessment practice among PTs in an inpatient sub-acute rehabilitation hospital.
      Implementation and evaluation of the intervention is underway.

PMID- 29659312
TI  - Anatomical distribution of musculoskeletal disorders following a road traffic
      collision in litigants presenting to physiotherapists within a private-clinic in
      North-East England.
AB  - INTRODUCTION: Musculoskeletal disorders (MSDs) are common following a road
      traffic collision (RTC) in England. Establishing the anatomical distribution of
      MSDs following RTC that present to physiotherapists may improve understanding and
      clinical practice. This study examined anatomical distribution of MSDs that
      present to physiotherapists within a litigant population following a RTC in
      England. METHODS: A retrospective review of physiotherapy records was conducted
      at a private practice in North-East England. Data were collected from 2105
      patients between January 2014 and December 2015. The primary outcome was
      anatomical regions with MSDs. Descriptive data is reported. RESULTS: Overall, 90%
      of patients presented with a neck/upper back disorder, while 52% presented with a
      lower back disorder. Of the assessed patients, 46% presented with one MSD, 45%
      presented with two MSDs while 9% presented with >=3 MSDs. Further analysis showed
      that those who presented to physiotherapy later and were not motor vehicle
      occupants (MVOs) were more likely to have upper-limb, lower-limb, or lumbar MSDs.
      Younger patients, who presented sooner and were non-MVO were more likely to have
      multiple regions affected by MSDs. CONCLUSIONS: This study presents
      epidemiological evidence that MSDs following a RTC occur primarily in the
      neck/upper back or lower back regions, and that multiple MSDs are common.

PMID- 29659313
TI  - Shoulder external rotation range of motion and pectoralis minor length in
      individuals with and without shoulder pain.
AB  - BACKGROUND: There is evidence that pectoralis minor (PM) length influences
      scapula position and that scapula position relates to glenohumeral joint (GHJ)
      external rotation (ER) range of motion (ROM). OBJECTIVES: To explore the
      association between PM resting length and GHJ ER ROM in individuals with and
      without shoulder pain. The influence of GHJ ER ROM measurement position on this
      association was also evaluated. DESIGN: Cross-Sectional. METHODS: Fifty
      individuals (25 asymptomatic and 25 with shoulder pain) participated. PM resting
      length was measured using a tape measure with subjects standing, while GHJ ER ROM
      was quantified using a digital inclinometer with participants in both supine and
      seated positions. The same blinded investigator took all measurements.
      RESULTS/FINDINGS: A significant negative correlation between PM resting length
      and GHJ ER ROM in the seated position was noted in the asymptomatic group (r = 
      0.41; p = 0.04), but not in the symptomatic group (r = -0.33; p = 0.11). A
      nonsignificant negative correlation was also demonstrated in the supine position
      for both groups (r ranged from -0.35 to -0.17; p > 0.05). There was a significant
      group x position interaction (F = 4.06; p = 0.04) with more GHJ ER ROM (6.80
      degrees ) for asymptomatic group in the seated position. CONCLUSIONS: PM length
      is not strongly correlated with GHJ ER ROM in individuals with or without
      shoulder pain. However, the position in which GHJ ER ROM is measured influenced
      the motion in asymptomatic individuals.

PMID- 29659314
TI  - Level of physical activity in men and women with chronic stroke.
AB  - INTRODUCTION: Community-dwelling stroke survivors generally show low levels of
      physical activity (PA). An improved understanding of the factors influencing
      participation in PA after stroke is imperative to improve levels of PA.
      Furthermore, gender differences in PA have received little attention in stroke
      research. The objective of this study was to examine gender differences in PA,
      physical functioning and psychological factors and the association between these
      factors and PA in men and women 1-3-year post-stroke. MATERIALS AND METHODS: A
      total of 187 community-dwelling individuals with stroke (65-85 years old, 29%
      women) were included in a secondary analysis based on data from a cross-sectional
      study. The exclusion criteria were severe cognitive or language dysfunction or
      dementia. The level of PA was measured by the Physical Activity Scale for the
      Elderly. Physical function included balance, walking speed and mobility.
      Psychological factors included depression, health-related quality of life and
      fall-related self-efficacy. Falls and fear of falling were each measured with a
      single question. RESULTS: There were no significant differences in PA levels
      between men and women. In multiple regression analyses, walking speed (p < 0.001)
      was associated with PA in men, and balance (p = 0.038) was associated with PA in
      women. CONCLUSIONS: The results indicate that strategies to increase PA levels 1
      3-year post-stroke could be improved by considering gender-specific factors.

PMID- 29659315
TI  - Association between pain drawing and psychological factors in musculoskeletal
      chronic pain: A systematic review.
AB  - BACKGROUND: It has been speculated that there is an association between pain area
      and psychological factors in chronic musculoskeletal pain conditions; however,
      this relation is not well established. PURPOSE: To investigate the association
      between pain distribution and psychological factors in chronic musculoskeletal
      pain conditions. STUDY DESIGN: Systematic review. METHODS: We searched the
      following databases using optimized search strategies: MEDLINE, PsycINFO, Scopus,
      Web of Science and Cochrane. Studies were included if they investigated the
      relation between pain area using a pain drawing (PD) and psychological factors
      measured by any consistent available method. RESULTS: Eleven articles were
      included. A total of 1301 participants with different musculoskeletal pain
      conditions, including low back pain, whiplash-associated disorders and
      fibromyalgia took part in the studies. In three studies, the correlation between
      pain area and depression was weak (r = 0.15, p = N/A; r = 0.26, p < 0.05; r =
      0.25, p = 0.01). Depression seemed to be a risk factor for pain in more body
      areas in one study (relative risk = 6.09, 95% CI = 1.1-33.5; p < 0.05). The
      relation between pain area and other psychological factors such as anxiety,
      kinesiophobia, catastrophizing, memory disturbances and concentration
      difficulties was also reported. CONCLUSIONS: A definitive answer on the relation
      of psychological factors and pain area is not available; the findings suggest
      that only depression might have a weak relation with pain area. Future studies
      that investigate sensory, psychological, emotional, cognitive and behavioral
      aspects, and also more accurate methods of PD assessment, are needed.

PMID- 29659316
TI  - Longitudinal changes in gray matter regions after cranial radiation and
      comparative analysis with whole body radiation: a DTI study.
AB  - PURPOSE: Radiation-induced white matter changes are well known and vastly
      studied. However, radiation-induced gray matter alterations are still a research
      question. In the present study, these changes were assessed in a longitudinal
      manner using Diffusion Tensor Imaging (DTI) and further compared for cranial and
      whole body radiation exposure. MATERIALS AND METHODS: Male mice (C57BL/6) were
      irradiated with cranial or whole body radiation followed by DTI study at 7T
      animal MRI system during predose, subacute and early delayed phases of radiation
      sickness. Fractional anisotropy (FA) and mean diffusivity (MD) values were
      obtained from brain's gray matter regions. RESULTS: Decreased FA with increased
      MD was observed prominently in animals exposed to cranial radiation showing most
      changes at 8 months post irradiation. However, whole body radiation induced FA
      changes were mostly observed at 1 month post irradiation as compared to controls.
      CONCLUSIONS: The differential response after whole body and cranial irradiation
      observed in the study depicts that radiation exposure of 5 Gy could induce
      permanent alterations in gray matter regions prominently as observed in
      Caudoputamen region at all the time points. Thus, our study has bolstered the
      role of DTI to probe microstructural changes in gray matter regions of brain
      after radiation exposure.

PMID- 29659317
TI  - Multiple response optimisation of processing and formulation parameters of pH
      sensitive sustained release pellets of capecitabine for targeting colon.
AB  - PURPOSE: To optimise the Eudragit/Surelease(r)-coated pH-sensitive pellets for
      controlled and target drug delivery to the colon tissue and to avoid frequent
      high dosing and associated side effects which restrict its use in the colorectal
      cancer therapy. METHODS: The pellets were prepared using extrusion-spheronisation
      technique. Box-Behnken and 32 full factorial designs were applied to optimise the
      process parameters [extruder sieve size, spheroniser-speed, and spheroniser-time]
      and the coating levels [%w/v of Eudragit S100/Eudragit-L100 and Surelease(r)],
      respectively, to achieve the smooth optimised size pellets with sustained drug
      delivery without prior drug release in upper gastrointestinal tract (GIT).
      RESULTS: The design proposed the optimised batch by selecting independent
      variables at; extruder sieve size (X1 = 1 mm), spheroniser speed (X2 = 900
      revolutions per minute, rpm), and spheroniser time (X3 = 15 min) to achieve
      pellet size of 0.96 mm, aspect ratio of 0.98, and roundness 97.42%. The 16%w/v
      coating strength of Surelease(r) and 13%w/v coating strength of Eudragit showed
      pH-dependent sustained release up to 22.35 h (t99%). The organ distribution study
      showed the absence of the drug in the upper part of GIT tissue and the presence
      of high level of capecitabine in the caecum and colon tissue. Thus, the presence
      of Eudragit coat prevent the release of drug in stomach and the inner
      Surelease(r) coat showed sustained drug release in the colon tissue. CONCLUSION:
      The study demonstrates the potential of optimised Eudragit/Surelease(r)-coated
      capecitabine-pellets for effective colon-targeted delivery system to avoid
      frequent high dosing and associated systemic side effects of drug.

PMID- 29659318
TI  - Synthesis, characterization, radiolabeling and biodistribution of a novel
      cyclohexane dioxime derivative as a potential candidate for tumor imaging.
AB  - PURPOSE: Dioxime derivative is reported to exhibit high affinity towards tumor
      cells. The objective of the present study is to synthesize a new dioxime
      derivative to be labeled with technetium-99m for using as a solid tumor marker.
      MATERIALS AND METHODS: ((2E,2',3E,3')-3,3'-(cyclohexane-1,2-diylbis
      (azanylylidene)) bis-(butan-2-one)dioxime) was synthesized by condensation of
      Butan-2,3-dione monooxime and diaminocyclohexane and labeled with 99mTc. The in
      vivo distribution of the agent was studied by carrying out biodistribution in
      tumor bearing Albino mice. RESULTS: A new cyclohexane dioxime derivative was
      synthesized with a good yield of 93 +/- 2% and its complexation with 99mTc was
      prepared with 85 +/- 4% radiochemical yield under the optimized conditions and
      the preparation exhibited in-vitro stability up to 6 h. Biodistribution studies
      showed high uptake in tumor cells with T/NT (target to non-target ratio) = 3.4 +/
      0.2 after 0.5 h post injection. CONCLUSION: As a result of biodistribution
      studies, the newly synthesized cyclohexane dioxime derivative showed its good
      uptake in tumor cells, which affords a potential radiopharmaceutical that could
      be used as a good tumor imaging agent.

PMID- 29659319
TI  - Disposition of tris(4-chlorophenyl)methanol and tris(4-chlorophenyl)methane in
      male and female Harlan Sprague Dawley rats and B6C3F1/N mice following oral and
      intravenous administration.
AB  - Tris(4-chlorophenyl)methane (TCPME) and tris(4-chlorophenyl)methanol (TCPMOH)
      have been detected in various biota and human tissues. The current studies were
      undertaken to investigate the disposition and metabolism of TCPME and TCPMOH in
      rats and mice. [14C]TCPME was well absorbed (>=66%) in male rats and mice
      following a single oral administration of 1, 10, or 100 mg/kg. The excretion of
      [14C]TCPME-derived radioactivity in urine (<=2.5%) and feces (<=18%) was low. The
      administered dose was retained in tissues (>= 64%) with adipose containing the
      highest concentrations. The metabolism of TCPME was minimal. The disposition and
      metabolism of [14C]TCPME in females was similar to males. The time to reach
      maximum concentration was <=7 h, the plasma elimination half-life was >=31 h, and
      the bioavailability was >=82% following a 10 mg/kg oral dose of [14C]TCPME in
      male rats and mice. The disposition of [14C]TCPMOH was similar to that of
      [14C]TCPME. Following an intravenous administration of [14C]TCPME or [14C]TCPMOH
      in male rats and mice, the pattern of disposition was similar to that of oral
      administration. In conclusion, both TCPME and TCPMOH are readily absorbed and
      highly bioavailable following a single oral administration pointing to importance
      of assessing the toxicity of these chemicals.

PMID- 29659320
TI  - Opioid Discussion in the Twittersphere.
AB  - BACKGROUND: The rise in opioid use and overdose has increased the importance of
      improving data collection methods for the purpose of targeting resources to high
      need populations and responding rapidly to emerging trends. OBJECTIVE: To
      determine whether Twitter data could be used to identify geographic differences
      in opioid-related discussion and whether opioid topics were significantly
      correlated with opioid overdose death rate. METHODS: We filtered approximately 10
      billion tweets for keywords related to opioids between July 2009 and October
      2015. The content of the messages was summarized into 50 topics generated using
      Latent Dirchlet Allocation, a machine learning analytic tool. The correlation
      between topic distribution and census region, census division, and opioid
      overdose death rate were quantified. RESULTS: We evaluated a tweet cohort of
      84,023 tweets from 72,211 unique users across the US. Unique opioid-related
      topics were significantly correlated with different Census Bureau divisions and
      with opioid overdose death rates at the state and county level. Drug-related
      crime, language of use, and online drug purchasing emerged as themes in various
      Census Bureau divisions. Drug-related crime, opioid-related news, and pop culture
      themes were significantly correlated with county-level opioid overdose death
      rates, and online drug purchasing was significantly correlated with state-level
      opioid overdoses. CONCLUSIONS: Regional differences in opioid-related topics
      reflect geographic variation in the content of Twitter discussion about opioids.
      Analysis of Twitter data also produced topics significantly correlated with
      opioid overdose death rates. Ongoing analysis of Twitter data could provide a
      means of identifying emerging trends related to opioids.

PMID- 29659321
TI  - The influence of redox status on inter-individual variability in the response of
      human peripheral blood lymphocytes to ionizing radiation.
AB  - PURPOSE: Ionizing radiation (IR) can act on atomic structures, producing damage
      to biomolecules. Earlier investigations evaluating individual radiosensitivity in
      vitro were focused on cytogenetic biomarkers (chromosomal aberrations - CA and
      micronuclei - MN). Since IR can also cause oxidative damage by producing reactive
      oxygen species, the main goal of this investigation was to establish the
      influence of redox status on CA and MN frequency in human peripheral blood
      lymphocytes. MATERIALS AND METHODS: Blood samples from 56 healthy donors were
      irradiated at doses of 0, 0.75, 1.5 and 3 Gy and then analyzed cytogenetically
      and biochemically. RESULTS: The results showed inter-individual variability in
      all analyzed parameters, as well as dose-dependent increases in almost all of
      them. Correlation analysis indicated no association between CA, MN and oxidative
      stress parameters. However, findings for overall response (HRR) parameters showed
      that donors with lower values for parameters of antioxidant status had increased
      levels of cytogenetic damage and higher responses to irradiation and vice versa.
      CONCLUSION: Besides well-established cytogenetic biomarkers of radiation
      exposure, our results indicated promising future use for biochemical oxidative
      status parameters in routine radiation protection practice, since together they
      can provide a complete radiation response profile in cases of continuous low-dose
      exposure, as well as in a radiation emergency.

PMID- 29659323
TI  - How strong is the Social Security safety net? Using the Elder Index to assess
      gaps in economic security.
AB  - Older Americans rely heavily on Social Security benefits (SSBs) to support
      independent lifestyles, and many have few or no additional sources of income. We
      establish the extent to which SSBs adequately support economic security,
      benchmarked by the Elder Economic Security Standard Index. We document
      variability across U.S. counties in the adequacy levels of SSBs among older
      adults. We find that the average SSBs fall short of what is required for economic
      security in every county in the United States, but the level of shortfall varies
      considerably by location. Policy implications relating to strengthening Social
      Security and other forms of retirement income are discussed.

PMID- 29659322
TI  - Applications of FT-NIRS combined with PLS multivariate methods for the detection
      & quantification of saccharin adulteration in commercial fruit juices.
AB  - Detection of adulteration in carbohydrate-rich foods like fruit juices is
      particularly difficult because of the variety of the commercial sweeteners
      available that match the concentration profiles of the major carbohydrates in the
      foods. In present study, a new sensitive and robust assay using Fourier Transform
      Near-Infrared Spectroscopy (FT-NIRS) combined with partial least square (PLS)
      multivariate methods has been developed for detection and quantification of
      saccharin adulteration in different commercial fruit juice samples. For this
      investigation, six different commercially available fruit juice samples were
      intentionally adulterated with saccharin at the following percentage levels: 0%,
      0.10%, 0.30%, 0.50%, 0.70%, 0.90%, 1.10%, 1.30%, 1.50%, 1.70% and 2.00%
      (weight/volume). Altogether, 198 samples were used including 18 pure juice
      samples (unadulterated) and 180 juice samples adulterated with saccharin. PLS
      multivariate methods including partial least-squares discriminant analysis (PLS
      DA) and partial least-squares regressions (PLSR) were applied to the obtained
      spectral data to build models. The PLS-DA model was employed to differentiate
      between pure fruit juice samples and those adulterated with saccharin. The R2
      value obtained for the PLS-DA model was 97.90% with an RMSE error of 0.67%.
      Similarly, a PLS regression model was also developed to quantify the amount of
      saccharin adulterant in juice samples. The R2 value obtained for the PLSR model
      was 97.04% with RMSECV error of 0.88%. The employed model was then cross
      validated by using a test set which included 30% of the total adulterated juice
      samples. The excellent performance of the model was proved by the low root mean
      squared error of prediction value of 0.92% and the high correlation factor of
      0.97. This newly developed method is robust, nondestructive, highly sensitive and
      economical.

PMID- 29659324
TI  - Montelukast attenuates radioactive I131-induced pulmonary damage on rats.
AB  - PURPOSE: Radioactive I131 (RAI) therapy is a standard method to ablate the
      remnant thyroidal tissue after total thyroidectomy and its metastases in
      differentiated thyroid carcinomas; however, I131 also accumulates in nonthyroidal
      tissue, which may cause adverse effects and limit the I131 dose required for
      treatment. We hypothesized that montelukast, a known agent with anti-inflammatory
      and anti-oxidant properties, would ameliorate the radiation-induced
      histopathological characteristics such as pneumonitis and fibrosis in rat lungs
      after RAI. METHODS: Fifty female Wistar albino rats were randomly separated into
      five groups of 10. Group 1 was the control group; Group 2 was administered RAI
      only; Group 3 was administered RAI and montelukast, Group 4 was administered RAI
      after total thyroidectomy and Group 5 was administered RAI and montelukast after
      total thyroidectomy. All rats were sacrificed after 12 weeks and the lungs were
      evaluated in the histological examination to determine the degree of inflammation
      and fibrosis and for immunohistochemical (IHC) staining for tissue expression of
      IL-1, IL-6 and TNF-alpha and TGF-beta. RESULTS: The RAI-administered groups,
      Group 2 and Group 4, were significantly different from the control group,
      however, the groups medicated with both RAI and montelukast, Group 3 and Group 5,
      were not significantly different from the control group. All histopathological
      and IHC parameters were significantly less in the groups administered with
      montelukast compared to the groups not administered with montelukast.
      CONCLUSIONS: The results of this study demonstrated the radioprotective effect of
      montelukast in the pulmonary system through histopathological and IHC
      examination.

PMID- 29659325
TI  - Reactive oxygen species mediates 50-Hz magnetic field-induced EGF receptor
      clustering via acid sphingomyelinase activation.
AB  - PURPOSE: Exposure to extremely low frequency electromagnetic fields (ELF-EMFs)
      could elicit biological effects including carcinogenesis. However, the detailed
      mechanisms by which these ELF-EMFs interact with biological system are currently
      unclear. Previously, we found that a 50-Hz magnetic field (MF) exposure could
      induce epidermal growth factor receptor (EGFR) clustering and phosphorylation on
      cell membranes. In the present experiment, the possible roles of reactive oxygen
      species (ROS) in MF-induced EGFR clustering were investigated. MATERIALS AND
      METHODS: Human amnion epithelial (FL) cells were exposed to a 50-Hz MF with or
      without N-acetyl-l-cysteine (NAC) or pyrrolidine dithiocarbamate (PDTC). EGFR
      clustering on cellular membrane surface was analyzed using confocal microscopy
      after indirect immunofluorescence staining. The intracellular ROS level and acid
      sphingomyelinase (ASMase) activity were detected using an ROS assay kit and an
      Amplex(r) Red Sphingomyelinase Assay Kit, respectively. RESULTS: Results showed
      that exposure of FL cells to a 50-Hz MF at 0.4 mT for 15 min significantly
      enhanced the ROS level, induced EGFR clustering and increased ASMase activity.
      However, pretreatment with NAC or PDTC, the scavenger of ROS, not only
      counteracted the effects of a 50-Hz MF on ROS level and AMS activity, but also
      inhibited the EGFR clustering induced by MF exposure. CONCLUSIONS: The present
      and previous data suggest that ROS mediates the MF-induced EGFR clustering via
      ASMase activation.

PMID- 29659326
TI  - Author reply to VA-MENGOC-BC cross-protection (2018HV0022).

PMID- 29659327
TI  - Rehabilitative vs palliative care for the temporomandibular joint disc
      displacement patient.

PMID- 29659328
TI  - Outsourcing within the Nordic context: Care services for older people in Finland.
AB  - The early 1990s economic setback brought significant reforms favoring the
      outsourcing of care in Finnish municipalities. Here, outsourcing refers to the
      practice of municipalities employing private organizations through different
      means (e.g., open tendering) to deliver public care services. In this context,
      this study examines the growth in the outsourcing of service housing and home
      help services in 311 municipalities from 2001 to 2015 and investigates the
      municipal factors associated with outsourcing using four dimensions: care needs,
      population size, economic situation, and political ideology of the municipality.
      The findings reveal a steep increase in the outsourcing of home-help and service
      housing. Care needs of older people are the most influential factor for
      outsourcing, particularly for service housing. Overall, the findings show a
      growing trend in private care provision in Finnish municipalities.

PMID- 29659329
TI  - Cost-Effectiveness Analyses of the 21-Gene Assay in Breast Cancer: Systematic
      Review and Critical Appraisal.
AB  - Purpose Prior studies examining cost effectiveness of the 21-gene assay (Oncotype
      DX [ODX]) for women with hormone receptor-positive, early-stage breast cancer
      have yielded disparate results. We aimed to explore why these analyses may have
      yielded different conclusions. Methods We conducted a systematic literature
      review of cost-effectiveness analyses (CEAs) of ODX. We examined the extent to
      which the structure of CEA modeling, the assumptions of the models, and the
      selection of input parameters influenced cost-effectiveness estimates. We also
      explored the prevalence of industry funding and whether industry funding was
      associated with study designs favoring ODX. Results We identified 27 analyses, 15
      of which received industry funding. In 18 studies, the clinical characteristics
      (eg, tumor size and grade) commonly used to make chemotherapy decisions were not
      incorporated into simulation modeling; thus, these studies would favor ODX being
      cost effective and might not reflect clinical practice. Most studies ignored the
      heterogeneous effect of ODX on chemotherapy use; only five studies assumed that
      ODX would increase chemotherapy use for clinically low-risk patients but decrease
      chemotherapy use for clinically high-risk patients. No study used population
      based joint distributions of ODX recurrence score and tumor characteristics, and
      12 studies inappropriately assumed that chemotherapy would increase distant
      recurrence for the low recurrence score group; both approaches overestimated the
      benefits of ODX. Industry-funded studies tended to favor ODX; all five studies
      that reported ODX as being cost saving were industry funded. In contrast, two
      studies that reported an incremental cost-effectiveness ratio > $50,000 per
      quality-adjusted life-year were not funded by industry. Conclusion Although a
      majority of published analyses indicated that ODX is cost effective, they
      incorporated study designs that can increase the risk of bias.

PMID- 29659331
TI  - Comparative analysis of aging policy reforms in Argentina, Chile, Costa Rica, and
      Mexico.
AB  - This investigation uses case studies and comparative analysis to review and
      analyze aging policy in Argentina, Chile, Costa Rica, and Mexico and uncovers
      similarities and relevant trends in the substance of historical and current aging
      policy across countries. Initial charity-based approaches to poverty and illness
      have been gradually replaced by a rights-based approach considering broader
      notions of well-being, and recent reforms emphasize the need for national,
      intersectoral, evidence-based policy. The results of this study have implications
      for understanding aging policy in Latin America from a welfare regime and policy
      makers' perspective, identifying priorities for intervention and informing policy
      reforms in developing countries worldwide.

PMID- 29659330
TI  - Treatment of Stage IV Favorable Histology Wilms Tumor With Lung Metastases: A
      Report From the Children's Oncology Group AREN0533 Study.
AB  - Purpose The National Wilms Tumor Study (NWTS) treatment of favorable histology
      Wilms tumor with lung metastases was vincristine/dactinomycin/doxorubicin (DD4A)
      and lung radiation therapy (RT). The AREN0533 study applied a new risk
      stratification and treatment strategy to improve event-free survival (EFS) while
      reducing exposure to lung RT. Methods Patients with favorable histology Wilms
      tumor and isolated lung metastases showing complete lung nodule response (CR)
      after 6 weeks of DD4A continued receiving chemotherapy without lung RT. Patients
      with incomplete response (IR) or loss of heterozygosity at chromosomes 1p/16q
      received lung RT and four cycles of cyclophosphamide/etoposide in addition to
      DD4A drugs (Regimen M). AREN0533 was designed to preserve a 4-year EFS of 85% for
      lung nodule CR and improve 4-year EFS from 75% to 85% for lung nodule IR. Results
      Among 292 assessable patients, 133 had CR and 159 had IR. For patients with CR, 4
      year EFS and overall survival (OS) estimates were 79.5% (95% CI, 71.2% to 87.8%)
      and 96.1% (95% CI, 92.1% to 100%), respectively. Expected versus observed event
      rates were 15% and 20.2% ( P = .052), respectively. For patients with IR, 4-year
      EFS and OS estimates were 88.5% (95% CI, 81.8% to 95.3%) and 95.4% (95% CI, 90.9%
      to 99.8%), respectively. Expected versus observed event rates were 25% and 12.2%
      ( P < .001), respectively. Overall, 4-year EFS and OS were 85.4% (95% CI, 80.5%
      to 90.2%) and 95.6% (95% CI, 92.8% to 98.4%) compared with 72.5% (95% CI, 66.9%
      to 78.1%; P < .001) and 84.0% (95% CI, 79.4% to 88.6%; P < .001), respectively,
      in the predecessor NWTS-5 study. Conclusion Excellent OS was achieved after
      omission of primary lung RT in patients with lung nodule CR, although there were
      more events than expected. EFS was significantly improved, with excellent OS, in
      patients with lung nodule IR using four cycles of cyclophosphamide/etoposide in
      addition to DD4A drugs. The overall AREN0533 treatment strategy yielded EFS and
      OS estimates that were superior to previous studies.

PMID- 29659332
TI  - Learning from your mistakes: does it matter if you're out in left foot, I mean
      field?
AB  - Studies have shown that generating errors prior to studying information (pencil
      ?) can improve target retention relative to passive (i.e., errorless) study,
      provided that cues and targets are semantically related (pencil-ink) and not
      unrelated (pencil-frog). In two experiments, we manipulated semantic proximity of
      errors to targets during trial-and-error to examine whether it would modulate
      this error generation benefit. In Experiment 1, participants were shown a cue
      (band-?) and asked to generate a related word (e.g., drum). Critically, they were
      given a target that either matched the semantic meaning of their guess (guitar)
      or mismatched it (rubber). In Experiment 2, participants studied Spanish words
      where the English translation either matched their expectations (pariente
      relative) or mismatched it (carpeta-folder). Both experiments show that errors
      benefit memory to the extent that they overlap semantically with targets. Results
      are discussed in terms of the retrieval benefits of activating related concepts
      during learning.

PMID- 29659333
TI  - Floc Performance parameters during water treatment in a micro-vortex flocculation
      process determined by machine vision.
AB  - The coagulant dosage of an existing water plant is mainly determined based on the
      experience of water treatment process and influent/effluent water quality indexes
      that have time hysteresis effects. To solve this problem, the effect of coagulant
      dosage on a number of parameters used to evaluate the efficiency of flocculation
      in a setup was determined by using the micro-vortex flocculation technology in
      conjunction with the investigation of the relation between the equivalent
      diameter and the fractal dimension. By means of the machine vision system and
      computerized analysis, the effects of floc quantity, floc equivalent diameter and
      fractal dimension can be assessed. The correlations of these parameters with
      turbidity and zeta potential of the settling water, taken as measures for
      effluent quality, were explored. The study results show that the optimal
      flocculation effect with a turbidity removal rate of 97.9% is achieved at the
      poly-aluminum chloride dosage of 20 mg/L. Meanwhile, a power exponential relation
      between the floc equivalent diameter and the fractal dimension was established
      with a correlation coefficient R2 of 0.826; relations among the effluent
      turbidity and the floc quantity, equivalent diameter, fractal dimension were
      established with a correlation coefficient R2 of 0.982, 0.851, and 0.875,
      respectively; equations between the zeta potential and the floc quantity,
      equivalent diameter, fractal dimension were also established where the
      correlation coefficient R2 were 0.868, 0.879, and 0.942, respectively. These
      results may provide excellent reference data for water plants to feed back the
      coagulant by floc performance parameters, which could relieve the hysteresis
      effect efficiently.

PMID- 29659334
TI  - Influencing Republicans' and Democrats' attitudes toward Obamacare: Effects of
      imagined vicarious cognitive dissonance on political attitudes.
AB  - The field of experimental social psychology is appropriately interested in using
      novel theoretical approaches to implement change in the social world. In the
      current study, we extended cognitive dissonance theory by creating a new
      framework of social influence: imagined vicarious dissonance. We used the
      framework to influence attitudes on an important and controversial political
      attitude: U.S. citizens' support for the Affordable Care Act (ACA). 36
      Republicans and 84 Democrats were asked to imagine fellow Republicans and
      Democrats, respectively, making attitude discrepant statements under high and low
      choice conditions about support for the ACA. The data showed that vicarious
      dissonance, established by imagining a group member make a counterattitudinal
      speech under high-choice conditions (as compared to low-choice conditions),
      resulted in greater support for the Act by Republicans and marginally diminished
      support by Democrats. The results suggest a promising role for the application of
      vicarious dissonance theory to relevant societal issues and for further
      understanding the relationship of dissonance and people's identification with
      their social groups.

PMID- 29659335
TI  - Lymphatics and the Pathogenesis of Hypertension.

PMID- 29659337
TI  - Hyperandrogenic athletes: performance differences in elite-standard 200m and 800m
      finals.
AB  - The purpose of this study was to examine whether the difference in elite-standard
      track and field performance between women athletes with and without
      hyperandrogenism reaches the 10-12% difference in performance between men and
      women, using only results from elite-standard track and field final competitions.
      Officially available data from two hyperandrogenic women (Caster Semenya and
      Dutee Chand) were compared with the characteristic performance of 200m and 800m
      elite-standard finals. The finishing times of Caster Semenya, before her
      ineligibility to compete in 2009 and after the suspension of the 2011 IAAF
      Hyperandrogenism Regulations were found to be respectively 1.24% and 1.49% faster
      than the predicted performance in 800m finals. When compared with the result of
      the second classified, the difference was respectively 0.65% and 2.08%. The
      analysis of the finishing times of Dutee Chand did not lead to any conclusions
      due to the lack of available data. The present study indicates that the
      percentage difference in performance between women with and women without
      hyperandrogenism does not reach the 3% difference requested by the Court of
      Arbitration for Sport for the reinstatement of the Hyperandrogenism Regulations,
      neither does it reach the 10% accepted range of difference in performance between
      men and women.

PMID- 29659338
TI  - An Improved PCR Protocol For Detection of Babesia duncanI In Wildlife and Vector
      Samples.
AB  - Human babesiosis is a tick-borne protozoal disease of increasing clinical
      significance in North America. Most cases in the eastern and Midwestern regions
      of the United States are reportedly due to Babesia microti infections. By
      contrast, most human infections reported in California and Washington have been
      attributed to a new species that was first identified in 1991 and subsequently
      named Babesia duncani. Although the tick vector and mammalian reservoir hosts for
      B. microti are well characterized, the vector and reservoir hosts for B. duncani
      are unknown. As a result, specific risk factors for human infections cannot be
      characterized. Identification of potential hosts and vector species has been
      hampered by the lack of specific and sensitive molecular diagnostic tools to
      amplify parasite DNA. To address this need, a nested PCR assay targeting the beta
      tubulin gene, a well-conserved locus in piroplasm parasites with a highly
      variable intron region among species, was developed. The assay was evaluated by
      spiking tick and mammalian DNA extracts with DNA from a B. duncani isolate
      derived from a human patient (WA-1) as well as related Babesia spp. from
      Californian wildlife. This assay was highly specific, with a sensitivity of
      approximately 1 copy of template DNA in a background of tick DNA. At this level
      of detection B. duncani was detectable in larval tick samples, and the target
      locus allowed for visual differentiation between species by gel electrophoresis.
      This assay offers researchers a new tool for elucidating the natural transmission
      cycle of B. duncani.

PMID- 29659339
TI  - Failure of eruption of first permanent molar teeth: a diagnostic challenge.
AB  - Ankylosis, mechanical and primary failure of eruption of molar teeth are rare and
      often difficult to distinguish between. All may have significant repercussions on
      the occlusion and successful management may involve invasive procedures. We
      present a case where an initial presentation characteristic of mechanical failure
      of eruption (ankylosis) of a first permanent molar tooth was excluded following a
      period of monitoring. Subsequent relief of crowding using a removable and then
      sectional fixed orthodontic appliance allowed spontaneous eruption of the tooth
      obviating the need for surgical intervention. This case highlights the
      utilisation of conservative treatment options until a diagnosis was confirmed to
      minimise the risk of iatrogenic damage and unnecessary treatment.

PMID- 29659340
TI  - Is Implicit Theory of Mind a Real and Robust Phenomenon? Results From a
      Systematic Replication Study.
AB  - Recently, theory-of-mind research has been revolutionized by findings from novel
      implicit tasks suggesting that at least some aspects of false-belief reasoning
      develop earlier in ontogeny than previously assumed and operate automatically
      throughout adulthood. Although these findings are the empirical basis for far
      reaching theories, systematic replications are still missing. This article
      reports a preregistered large-scale attempt to replicate four influential
      anticipatory-looking implicit theory-of-mind tasks using original stimuli and
      procedures. Results showed that only one of the four paradigms was reliably
      replicated. A second set of studies revealed, further, that this one paradigm was
      no longer replicated once confounds were removed, which calls its validity into
      question. There were also no correlations between paradigms, and thus, no
      evidence for their convergent validity. In conclusion, findings from anticipatory
      looking false-belief paradigms seem less reliable and valid than previously
      assumed, thus limiting the conclusions that can be drawn from them.

PMID- 29659342
TI  - Lactation Education Accreditation and Approval Review Committee.

PMID- 29659341
TI  - Impediments to Effective Altruism: The Role of Subjective Preferences in
      Charitable Giving.
AB  - Charity could do the most good if every dollar donated went to causes that
      produced the greatest welfare gains. In line with this proposition, the effective
      altruism movement seeks to provide individuals with information regarding the
      effectiveness of charities in hopes that they will contribute to organizations
      that maximize the social return of their donation. In this research, we
      investigated the extent to which presenting effectiveness information leads
      people to choose more effective charities. We found that even when effectiveness
      information is made easily comparable across options, it has a limited impact on
      choice. Specifically, people frequently choose less effective charity options
      when those options represent more subjectively preferred causes. In contrast to
      making a personal donation decision, outcome metrics are used to a much greater
      extent when choosing financial investments and when allocating aid resources as
      an agent of an organization. Implications for effective altruism are discussed.

PMID- 29659343
TI  - JHL News.

PMID- 29659345
TI  - An Interview With Brooke Bauer, MPH.

PMID- 29659346
TI  - #MeToo Against Racism.

PMID- 29659347
TI  - Social Justice at the Core of Breastfeeding Protection, Promotion and Support: A
      Conceptualization.
AB  - Despite widespread awareness of the health benefits for both mothers and babies
      we are far from achieving universal breastfeeding. Breastfeeding rates globally
      are lower than recommended levels and there are concerns that some global
      breastfeeding efforts have stalled (1, 2). In addition, we see persistent
      disparities in breastfeeding rates by race, ethnicity, class and status (3). A
      growing literature documents how a range of injustices, including gender
      inequality (7), racism (8), poverty (9), and violence (10, 11) shape whether, how
      exclusive, and for how long mothers and others will be able to breastfeed or feed
      their infants human milk. These social injustices and inequities work to
      privilege breastfeeding even as the health message becomes more mainstreamed and
      human milk more desirable. A social justice approach could help us address the
      gender, race, and sexuality-based inequities and injustices in opportunities,
      resources, status, and power that are influencing the patterns of breastfeeding
      we see today. The 12th Breastfeeding and Feminism International Conference held
      in 2017 took as its theme Breastfeeding as Social Justice: From Crucial
      Conversation to Inspired Action. The planning team for that conference identified
      seven core domains that could help us conceptualize a framework for placing
      social justice at the core of our work. This paper presents this framework and
      suggestions for policy and practice that follow.

PMID- 29659348
TI  - Evaluation of estrogen and G protein-coupled estrogen receptor 1 (GPER) levels in
      drug-naive patients with attention deficit hyperactivity disorder (ADHD).
AB  - Estrogen has a crucial role in the regulation of reproductive and neuroendocrine
      function and exerts its effects through two classes of receptors, nuclear and
      membrane estrogen receptors (mERs). G protein-coupled estrogen receptor 1 (GPER)
      is a member of mERs, and despite limited research on the levels of GPER in
      patients with psychiatric diseases, a role of GPER in such conditions has been
      suggested. Here we evaluated serum estrogen and GPER levels in children with
      attention deficit hyperactivity disorder (ADHD) in relation to their age- and
      gender-matched healthy controls. A total of 82 children were included in the
      study, 47 drug- naive patients with ADHD (age: 6-12 years; male/female: 34/13)
      and 35 healthy controls (age: 6-12 years; male/female: 19/16). The subgroups
      according to ADHD types were inattentive, hyperactive/impulsive, and combined.
      Serum estrogen was measured using an immunoassay system, while serum GPER was
      determined using a commercial sandwich enzyme-linked immunosorbent assay kit.
      Estrogen levels in children with ADHD were similar as in control group, while
      GPER levels were significantly lower in ADHD group compared to controls (p <
      0.05). Logistic regression analysis showed a significant association between GPER
      levels and ADHD (p < 0.05), and no association between estrogen levels and ADHD
      (p > 0.05). No significant differences were found in GPER and estrogen levels
      between ADHD subgroups (p > 0.05). To the best of our knowledge, this study is
      the first to investigate estrogen and GPER levels in ADHD. Our preliminary
      findings suggest a relationship between serum GPER levels and ADHD, and this
      should be further investigated.

PMID- 29659349
TI  - Control of body temperature and immune function in patients undergoing open
      surgery for gastric cancer.
AB  - The influence of mild perioperative hypothermia on the immune function and
      incidence of postoperative wound infections has been suggested, but the specific
      mechanism is unclear. This study aimed to analyze the body temperature, immune
      function, and wound infection rates in patients receiving open surgery for
      gastric cancer. Body temperature was controlled in each patient using one of four
      different methods: wrapping limbs, head and neck; insulated blankets; warming
      infusion fluids and insulated blankets; and warming fluids without insulated
      blankets. One hundred patients were randomly divided into four groups of 25
      patients each, and every group received a different intraoperative treatment for
      maintaining normal body temperature. Nasopharyngeal and rectal temperatures,
      transforming growth factor beta (TGF-beta), interleukin 10 (IL-10) levels, and
      cluster of differentiation (CD)3+T and CD4+/CD25+ regulatory T cell (Treg) counts
      were measured before surgery and at 2 and 4 hours postoperatively. Patients were
      evaluated at one week after surgery for signs of infection. Intraoperative body
      temperature and measures of immune function varied significantly between the four
      groups, with the largest temperature changes observed in the group in which only
      the limbs were wrapped in cotton pads to control the body temperature. The lowest
      temperature change (i.e., close to normal temperature) and cytokine response
      after surgery were observed in the group in which infusion fluids and transfused
      blood (if needed) were heated to 37C, peritoneal irrigation fluid was heated to
      37C, and an insulation blanket was heated to 39C and placed under the patient. No
      intergroup differences were found in the infection rates at one week after
      surgery. In conclusion, body temperature variation during surgery affects the
      immune function of patients, and maintaining body temperature close to normal
      results in the least variation of immune function.

PMID- 29659350
TI  - Does dental caries affect dental development in children and adolescents?
AB  - Although a link between dietary changes, caries, and dental development has been
      observed, the literature provides little insight about this relationship. The aim
      of our study was to investigate the association between dental caries and dental
      development in a clinical sample of Albanian children and adolescents. In total,
      118 children and adolescents, born between 1995 and 2004 and aged 6-15 years,
      were included. Dental caries in the deciduous dentition was assessed using the
      Decayed, Filled Teeth (dft) index and dental caries in the permanent dentition
      was assessed using the Decayed, Missing, Filled Teeth (DMFT) index. Dental
      development during the permanent dentition was determined using the Demirjian
      method. Linear and ordinal regression models were applied to analyze the
      associations of dental caries with dental age and developmental stages of each
      left mandibular tooth. Dental caries in the deciduous dentition, estimated as a
      median dft of 2.0 (90% range, 0.0-9.1), was significantly associated with lower
      dental age (beta = -0.21; 90% CI: -0.29, -0.12) and with delayed development of
      the canine, both premolars, and the second molar. Untreated dental caries (dt)
      was associated with lower dental age (beta = -0.19; 90% CI: -0.28, -0.10). Dental
      caries in the permanent dentition, estimated as a median DMFT of 1.0 (90% range,
      0.0-8.0), was not significantly associated with dental age (beta = 0.05; 90% CI: 
      0.04, 0.14). However, the DMFT was associated with the advanced stages of
      development of both premolars and the second molar. The untreated dental caries
      in the deciduous dentition delays the development of permanent teeth.

PMID- 29659351
TI  - Control of voluntary and optogenetically perturbed locomotion by spike rate and
      timing of neurons of the mouse cerebellar nuclei.
AB  - Neurons of the cerebellar nuclei (CbN), which generate cerebellar output, are
      inhibited by Purkinje cells. With extracellular recordings during voluntary
      locomotion in head-fixed mice, we tested how the rate and coherence of inhibition
      influence CbN cell firing and well-practiced movements. Firing rates of Purkinje
      and CbN cells were modulated systematically through the stride cycle (~200-300
      ms). Optogenetically stimulating ChR2-expressing Purkinje cells with light steps
      or trains evoked either asynchronous or synchronous inhibition of CbN cells.
      Steps slowed CbN firing. Trains suppressed CbN cell firing less effectively, but
      consistently altered millisecond-scale spike timing. Steps or trains that
      perturbed stride-related modulation of CbN cell firing rates correlated well with
      irregularities of movement, suggesting that ongoing locomotion is sensitive to
      alterations in modulated CbN cell firing. Unperturbed locomotion continued more
      often during trains than steps, however, suggesting that stride-related
      modulation of CbN spiking is less readily disrupted by synchronous than
      asynchronous inhibition.

PMID- 29659353
TI  - [Genetic polymorphisms of thiopurine methyltransferase and incidence of adverse
      events in patients with medical indication of azathioprine].
AB  - Azathioprine is a thiopurine which has a narrow therapeutic index and marked
      hematological and hepatic toxicity. Thiopurine s-methyltransferase is an enzyme
      involved in the metabolism of thiopurines. Mutations in the gene that encodes the
      enzyme may augment the risk of adverse events. For that reason, pharmacogenetic
      determinations prior to the initiation of therapy can provide useful information
      for the future therapeutic strategy. Nevertheless, its utility in the local
      environment is not completely established. Forty-five subjects (13 men) who had
      been prescribed azathioprine were included. The presence of *2, *3A, *3B and *3C
      mutations were determined by PCR-RFLP, and the relationship between genotype and
      incidence of adverse events related to the drug was analyzed. Nine carried at
      least one non-functional allele, one of them with *3A/*3A genotype. Among the
      eighteen patients who initiated treatment with azathioprine, toxicity was
      detected in 3 cases: 2 mild events were observed in patients with normal
      genotype, and the only serious event (bone marrow suppression) occurred in the
      individual with homozygous mutant genotype. The only homozygous mutant patient
      developed the most severe of the registered events, in spite of being under
      treatment with low doses of azathioprine. This is the reason why enzymatic
      determination could be of utility, even though it does not replace clinical and
      biochemical follow-up in patients under thiopurine treatment.

PMID- 29659352
TI  - First spikes in visual cortex enable perceptual discrimination.
AB  - Visually guided perceptual decisions involve the sequential activation of a
      hierarchy of cortical areas. It has been hypothesized that a brief time window of
      activity in each area is sufficient to enable the decision but direct
      measurements of this time window are lacking. To address this question, we
      develop a visual discrimination task in mice that depends on visual cortex and in
      which we precisely control the time window of visual cortical activity as the
      animal performs the task at different levels of difficulty. We show that
      threshold duration of activity in visual cortex enabling perceptual
      discrimination is between 40 and 80 milliseconds. During this time window the
      vast majority of neurons discriminating the stimulus fire one or no spikes and
      less than 16% fire more than two. This result establishes that the firing of the
      first visually evoked spikes in visual cortex is sufficient to enable a
      perceptual decision.

PMID- 29659354
TI  - [Electrocardiographic differences between apical hypertrophic cardiomyopathy and
      apical non-ST segment myocardial infarction].
AB  - Apocal hypertrophic cardiomyopathy (AHCM) is a phenotypic variant within
      hypertrophic cardiomyopathies, in which ventricular repolarization alterations
      are present. These electrocardiographic disturbances can mimic an anterior
      infarction which triggers a series of studies and treatments that may be
      unnecessary. The aim of this study was to describe and compare
      electrocardiographic differences in a series of patients with AHCM and apical non
      ST segment elevation myocardial infarction in patients (NSTEMI) with T-wave
      changes. We conducted an observational and retrospective study, including
      patients with diagnosed AHCM (N = 19) and apical NSTEMI (N = 19) with negative T
      waves in V1 and V6 lead of the EKG. Those with AHCM presented higher T-wave
      voltage (7 mV vs. 5 mV, p = 0.001) and peak voltage (29 mV vs. 17 mV, p = 0.003),
      higher R-waves (25 mV vs. 10 mV, p = 0.0001), and a maximum voltage of R and T
      sum (R + T) significantly higher (33 vs. 14, p = 0.00001). They also showed a
      greater T-wave asymmetry, with a TiTp / TpTf ratio > 1. At a cut-off value of
      26.5 mV for the R + T variable, 68% sensitivity and 100% specificity were
      obtained to diagnose AHCM. This study shows the existence of major differences in
      electrocardiographic presentation of AHCM and apical NSTEMI.

PMID- 29659355
TI  - [Assessment of the use in adults of four vaccines: a population survey in
      Argentina].
AB  - Vaccination is one of the most effective strategies for disease prevention.
      Argentina initiated the transition from child vaccination to family vaccination
      through the incorporation of an adult schedule. One of the difficulties with this
      last group is to assess the percentage of use (PU) of the vaccines. With the aim
      of determining the PU of adult vaccines in Argentina, a vaccination module was
      included in the National Survey of Risk Factors carried out in 2013 by the
      National Ministry of Health. The sampling had a stratified multistage design. A
      total of 32 365 people = 18 year-old were surveyed about the use of four vaccines
      included in the National Vaccination Calendar: hepatitis B, tetanus, influenza,
      and pneumococcus. The entire population was surveyed for tetanus and hepatitis B
      while certain groups at risk were evaluated for influenza and pneumococcus,
      according to current recommendations. PU varied according to the vaccine
      analyzed: tetanus 49.8%, hepatitis B 21.7%, influenza 51.6% and pneumococcus
      16.2%. The main information sources on adult vaccination were media (television,
      internet, etc.) followed by health personnel (70.8% and 27.9%, respectively). The
      survey is a suitable tool to assess the use of vaccines by adults, identify low
      coverage populations, and to plan and implement strategies to improve coverage.

PMID- 29659356
TI  - Acromegaly: A rare disease?
AB  - Acromegaly is generally considered a benign and uncommon disease. However, some
      recent data bring support to the idea that it is more frequent than previously
      thought. Besides, acromegaly can significantly shorten the length of life due to
      its cardiovascular and metabolic complications. Since its clinical signs are
      insidiously progressive for many years, there is a considerable delay in its
      detection. Usually, many different specialists have been consulted before
      reaching diagnosis of acromegaly. Those specialists include cardiologists,
      pulmonologists, dentists, rheumatologists, and diabetes specialists. Possible
      means to achieve earlier detection are based on increasing awareness of doctors
      and the public in general. In this paper, the author analyzes the factors related
      to delayed diagnosis and the potential ways to ameliorate awareness of the
      disease with particular attention to screening procedures.

PMID- 29659357
TI  - [Post-stroke epilepsy].
AB  - Stroke is the most common cause of seizures and epilepsy in population stuies of
      adults. Seizures occur within 24 hours of the stroke in a high percent of
      patients. The pathogenesis of these early-onset seizures may be related to local
      ion shifts and release of high levels of excitotoxic neurotransmitters in the
      area of ischemic injury. The risk of late-onset seizures may increase over time,
      an underlying permanent lesion that leads to persistent chnges in neuronal
      excitability appears to be responsible for late-onset seizures after stroke. The
      most consistently identified risk factors for acute and late post-stroke seizures
      are stroke severity and cortical location. Most seizures following stroke are
      focal at onset, but secondary generalization is common, particularly in patients
      with late-onset seizures. Status epilepticus is relatively uncommon. The efficacy
      of antiepileptic drugs for these post-stroke seizures has not been rigorously
      assessed in controlled trials, although most seizures can be controlled with a
      single agent. Given the relatively low frequency of recurrent seizures after
      stroke, and an absence of absolute predictors of poststroke epilepsy, the
      decision of when to treat patients for a post-stroke seizure is difficult.

PMID- 29659358
TI  - [Role of the enterocyte in type 2 diabetes mellitus associated dyslipidemia].
AB  - In type 2 diabetes mellitus there is an overproduction of chylomicron in the
      postprandial state that is associated with increased cardiovascular risk. Current
      evidence points out a leading role of enterocyte in dyslipidemia of type 2
      diabetes mellitus, since it increases the production of apolipoprotein B-48 in
      response to a raise in plasma free fatty acids and glucose. The chylomicron
      metabolism is regulated by many factors apart from ingested fat, including
      hormonal and metabolic elements. More recently, studies about the role of gut
      hormones, have demonstrated that glucagon-like peptide-1 decreases the production
      of apolipoprotein B-48 and glucagon-like peptide-2 enhances it. Insulin acutely
      inhibits intestinal chylomicron production in healthy humans, whereas this acute
      inhibitory effect on apolipoprotein B-48 production is blunted in type 2 diabetes
      mellitus. Understanding these emerging regulators of intestinal chylomicron
      secretion may offer new mechanisms of control for its metabolism and provide
      novel therapeutic strategies focalized in type 2 diabetes mellitus postprandial
      hyperlipidemia with the reduction of cardiovascular disease risk.

PMID- 29659359
TI  - [Pneumonia associated with mechanical ventilation. Update and recommendations
      inter- Societies SADI-SATI].
AB  - Representatives of the Argentine Society of Infectious Diseases (SADI) and the
      Argentine Society of Intensive Therapy (SATI) worked together on the development
      of specific recommendations for the diagnosis, treatment and prevention of
      ventilator-associated pneumonia (VAP). The methodology used was the analysis of
      the literature published in the last 15 years, complemented with the opinion of
      experts and local data. This document aims to offer basic tools to optimize
      diagnosis based on clinical and microbiological criteria, orientation in
      empirical and targeted antibiotic schemes, news on posology and administration of
      antibiotics in critical patients and to promote effective measures to reduce the
      risk of VAP. It also offers a diagnostic and treatment algorithm and
      considerations on inhaled antibiotics. The joint work of both societies 
      infectious diseases and intensive care- highlights the concern for the management
      of VAP and the importance of ensuring improvement in daily practices. This
      guideline established recommendations to optimize the diagnosis, treatment and
      prevention of VAP in order to reduce morbidity and mortality, days of
      hospitalization, costs and resistance to antibiotics due to misuse of
      antimicrobials.

PMID- 29659360
TI  - [Development of a product anti-Shiga toxin for prevention of the hemolytic uremic
      syndrome].
AB  - The typical hemolytic uremic syndrome (HUS) is an orphan disease caused by Shiga
      toxin(Stx) producing Escherichia coli strains and characterized by acute kidney
      damage, microangiopathic hemolytic anemia and low platelet count. It is endemic
      in Argentina, the country with the highest incidence of HUS in the world. Stx is
      essential for its development and therefore, HUS is considered a toxemic non
      bacteremic disorder, which could be treated with antibodies. Herein we describe
      the development of a new treatment capable of neutralizing the toxic effect of
      Stx and its variants. The treatment consists of F(ab')2 fragments from an equine
      antiserum whose efficacy and potency against Stx1 and Stx2 were proved in
      different preclinical models. The product was shown to be safe in animals.
      Furthermore, the anti-Stx F(ab')2 pharmacokinetic was shown to be similar to that
      of analogous compounds and a therapeutic window for its administration was
      determined. Altogether, these preclinical results warrant testing in humans. The
      phase I clinical trial will be performed at the Hospital Italiano in Buenos Aires
      to evaluate the safety and pharmacokinetics of the product in healthy adult
      volunteers. Based on the results of this study, a phase II clinical trial will be
      planned in pediatric patients diagnosed with infection by Stx-producing E. coli
      strains.

PMID- 29659361
TI  - [One hundred years after the "Spanish" flu].
AB  - The "Spanish" flu pandemic, which occurred a century ago, is considered the most
      devastating in human history. An estimated one third of world population fell ill
      with flu and more than 2.5% of them died. The course of the epidemic had two main
      waves (1918 and 1919) and showed an unusual W-shaped morbidity/mortality
      distribution. Death was not a direct outcome of flu itself but rather a
      consequence of secondary bacterial bronchopneumonia, for which antibiotics had
      not yet been discovered. Pre-existing pulmonary tuberculosis was also accountable
      for increased flu death rates during the pandemic. As it happened in Europe, in
      Argentina the epidemic had two main waves, with ample variation in mortality by
      region. Available treatment at the time included diet, throat antiseptic rinses,
      low doses of quinine valerianate, salicylates, codeine as a cough suppressant,
      and camphor oil. Primitive anti-pneumococcal vaccines and immune sera were also
      applied. Upon the disclosure of the whole RNA sequence of the 1918 influenza
      virus genome, by means of reverse genetics it was possible to assemble viral
      particles resembling those of the deadly pandemic. The reconstituted virus proved
      to be extraordinarily virulent for mice. Current seasonal flu vaccines help to
      reduce, but not to abolish, the risk of another pandemic. The ongoing development
      of "universal" vaccines against influenza conferring reliable and long-lasting
      immunity may prevent its global spread in the future.

PMID- 29659362
TI  - [Recurrent atypical hemolytic uremic syndrome after renal transplantation:
      treatment with eculizumab].
AB  - Atypical hemolytic uremic syndrome (aHUS) is a rare entity. It is characterized
      by a thrombotic microangiopathy (nonimmune hemolytic anemia, thrombocytopenia,
      and acute renal failure), with a typical histopathology of thickening of
      capillary and arteriolar walls and an obstructive thrombosis of the vascular
      lumen. The syndrome is produced by a genetic or acquired deregulation of the
      alternative pathway of the complement system, with high rates of end stage renal
      disease, post-transplant recurrence, and high mortality. Mutations associated
      with factor H, factor B and complement C3 show the worst prognosis. Even though
      plasma therapy is occasionally useful, eculizumab is effective both for treatment
      and prevention of post-transplant recurrence. We describe here an adult case of
      congenital aHUS (C3 mutation) under preventive treatment with eculizumab after
      renal transplantation, with neither disease recurrence nor drug-related adverse
      events after a 36-months follow-up.

PMID- 29659363
TI  - [Late diagnosis of WHIM sydrome].
AB  - WHIM syndrome is a primary autosomal dominant immuno deficiency due to CXCR4
      mutations characterized by mucocutaneous warts, hypogammaglobulinemia, recurrent
      bacterial infections and myelokathesis. Treatment consists in prophylactic
      antibiotics, immunoglobulin replacement and granulocyte or granulocyte/monocyte
      colony stimulating factors. We present the case of a 21 year old woman who showed
      leukopenia at 10 months of age and one year later multiple infections with
      hypogammaglobulinemia requiring intravenous immunoglobulin. During follow up she
      developed chronic neutropenia. A bone marrow aspiration showed increased myeloid
      series with predominance of immature elements. On the basis of infections, low
      levels of IgG, IgA, IgM and lymphopenia with absent memory B cells, a diagnosis
      of common variable immunodeficiency was made. She started intravenous
      immunoglobulin replacement and prophylactic antibiotics. At age 20, small warts
      in hands that progressed to forearms, knees, abdomen and face were recorded.
      CXCR4 gene sequencing was done detecting a heterozygous p.Arg334STOP mutation,
      confirming WHIM syndrome. This disease is infrequent and difficult to diagnose.

PMID- 29659364
TI  - [Association between central diabetes insipidus and type 2 diabetes mellitus].
AB  - Central diabetes insipidus is a rare disease of the hypothalamus and
      neurohypophysis. It is very unusually found in the adult with type 2 diabetes
      mellitus. It is manifested by a polydipsic polyuric syndrome, which must be
      distinguished from the poorly controlled type 2 diabetes mellitus. Given the
      similarity of both entities and the unusual nature of their coexistence, their
      suspicion is difficult. The case of a 72-year-old male with type 2 diabetes
      mellitus with poor insulin control (fasting hyperglycemia greater than 180 mg/dl)
      who had a long-standing polyuric syndrome is here presented. Hypernatremia and
      plasma osmolality elevated together with a low urinary osmolality led to the
      suspicion of diabetes insipidus, which was subsequently confirmed by the
      dehydration test and the administration of desmopressin sc. With 61% increase in
      the calculated urinary osmolarity one hour post desmopressin s.c., diabetes
      insipidus of central type was diagnosed. Nuclear Magnetic Resonance showed a
      bright spot with normal neurohypophysis, contributing to the diagnosis of the
      idiopathic form.

PMID- 29659365
TI  - [Association between diabetic ketoacidosis and acromegaly].
AB  - Diabetes mellitus occurs in nearly 10% of patients with acromegaly and is
      secondary to insulin resistance caused by high levels of growth hormone. Diabetes
      ketoacidosis has been described as a rare complication of acromegaly, resulting
      from a relative insulin deficiency caused by growth hormone excess. We described
      the case of a 38 year-old man who presented to the emergency room with a 6-week
      history of polydipsia, polyuria, polyphagia and weight loss. He also had nausea,
      vomiting and abdominal pain from two days before admission. His plasma glucose
      level was 880 mg/dl, plasma osmolarity 368 mOsm/l, arterial pH 7.06 and serum
      bicarbonate 8.6 mEq/l. At the clinical examination, he had features of
      acromegaly. Magnetic resonance imaging showed a pituitary macro adenoma and
      growth hormone dosages were abnormally high. After tumor removal, plasma glucose
      levels became normal. This case shows the rare association between diabetic
      ketoacidosis and acromegaly. Surgery, in this case, was the definite modality of
      treatment.

PMID- 29659367
TI  - [Answers by heart: hypertrophy and healing].

PMID- 29659366
TI  - [Epigenetics and hepatocellular carcinoma: ?a therapeutic opportunity?]

PMID- 29659368
TI  - [Screening for breast cancer and its potential damage].

PMID- 29659369
TI  - [The benefits of breast cancer screening outweigh the potential harm].

PMID- 29659370
TI  - Improving the photovoltaic performance of the all-solid-state TiO2 NR/CuInS2
      solar cell by hydrogen plasma treatment.
AB  - The interfacial properties of the heterojunction between p-type and n-type
      materials play an important role in the performance of the solar cell. In this
      paper, a p-type CuInS2 film was deposited on TiO2 nanorod arrays by spin coating
      to fabricate an all-solid-state solar cell and the TiO2 nanorod arrays were
      treated with hydrogen plasma(H:TiO2) to ameliorate the interfacial properties.
      The influence of the hydrogen plasma treatment on the performance of the solar
      cell was investigated. The short-circuit current density was obviously raised and
      the power conversion efficiency of the solar cell improved to 0.30%, which is
      three times that of solar cells without hydrogen plasma treatment. The
      enhancement of the performance is attributed to not only the enhancement of
      carrier separation and transport, but the reduction of the recombination of
      electrons and holes, which is caused by hydrogen plasma treatment.

PMID- 29659371
TI  - Real-world use, safety, and survival of ipilimumab in metastatic cutaneous
      melanoma in The Netherlands.
AB  - Phase III trials with ipilimumab showed an improved survival in patients with
      metastatic melanoma. We evaluated the use and safety of ipilimumab, and the
      survival of all patients with metastatic cutaneous melanoma (N=807) receiving
      ipilimumab in real-world clinical practice in The Netherlands using data from the
      Dutch Melanoma Treatment Registry. Patients who were registered between July 2012
      and July 2015 were included and analyzed according to their treatment status:
      treatment-naive (N=344) versus previously-treated (N=463). Overall, 70% of
      treatment-naive patients and 62% of previously-treated patients received all four
      planned doses of ipilimumab. Grade 3 and 4 immune-related adverse events occurred
      in 29% of treatment-naive patients and 21% of previously-treated patients. No
      treatment-related deaths occurred. Median time to first event was 5.4 months [95%
      confidence interval (CI): 4.7-6.5 months] in treatment-naive patients and 4.4
      months (95% CI: 4.0-4.7 months) in previously-treated patients. Median overall
      survival was 14.3 months (95% CI: 11.6-16.7 months) in treatment-naive patients
      and 8.7 months (95% CI: 7.6-9.6 months) in previously-treated patients. In both
      patient groups, an elevated lactate dehydrogenase level (hazard ratio: 2.25 and
      1.70 in treatment-naive and previously-treated patients, respectively) and
      American Joint Committee on Cancer M1c-stage disease (hazard ratio: 1.81 and
      1.83, respectively) were negatively associated with overall survival. These real
      world outcomes of ipilimumab slightly differed from outcomes in phase III trials.
      Although phase III trials are crucial for establishing efficacy, real-world data
      are of great added value enhancing the generalizability of outcomes of ipilimumab
      in clinical practice.

PMID- 29659372
TI  - Consequences of Antepartum Depression.
AB  - To counsel women about risks and benefits of depression treatment during
      pregnancy, clinicians must appreciate the potential consequences of untreated
      depression on the mother and her unborn child. Many studies have demonstrated
      associations between untreated depression during pregnancy and a range of adverse
      outcomes, including low birth weight, preterm delivery, preeclampsia, emergent
      operative delivery, postpartum depression, and both cognitive and behavioral
      deficits in the child. Although most of these associations are marked by low odds
      ratios and a host of potential confounding issues, they collectively provide
      considerable rationale for identifying depression in pregnancy and offering
      treatment for mothers at risk.

PMID- 29659373
TI  - Association of Academic Physiatrists Federal Funding of Disability and
      Rehabilitation Research Position Statement.
AB  - The Association of Academic Physiatrists seeks to advocate for policies that are
      supportive of academic rehabilitation, with elected officials, agency leaders,
      and other policy makers. Accordingly, the Association of Academic Physiatrists'
      Public Policy Committee identifies policy issues of importance to the
      organizational mission, conducts background research on those issues, and
      develops position statements that articulate the organization's position. These
      position statements require approval by the Board of Trustees and are used to
      support advocacy efforts by Association of Academic Physiatrists' members.
      Federal funding for disability and rehabilitation research is an important issue
      for the Association of Academic Physiatrists and its members. This position
      statement addresses the need for greater federal funding in this area, better
      coordination of the agencies providing funding, and an appropriate balance of
      merit-based funding with funding targeted to building capacity in critical
      rehabilitation-relevant methodology and content areas.

PMID- 29659374
TI  - Intravenous Immunoglobulin and Methylprednisolone for Clozapine-Associated
      Perimyocarditis.
AB  - CLINICAL FEATURES: Cardiotoxicity is a rare but serious side effect of clozapine.
      We present a case of a psychiatric patient on chronic clozapine 75 mg daily, who
      presented with congestive heart failure secondary to the cardiotoxic effects of
      the psychiatric medication. THERAPEUTIC CHALLENGE: Conventional heart failure
      treatment failed to improve symptoms. SOLUTION: A course of 40 mg of intravenous
      immunoglobulin and 125 mg of steroids was implemented, after which the patient
      made a full recovery. We hope to raise awareness of concurrent clozapine-induced
      pericarditis and myocarditis and propose a role of intravenous immunoglobulin and
      steroids in the treatment of drug-induced cardiomyopathy.

PMID- 29659375
TI  - Validity, Reliability, Feasibility, and Usefulness of Pain Monitor: A
      Multidimensional Smartphone App for Daily Monitoring of Adults With Heterogenous
      Chronic Pain.
AB  - OBJECTIVES: Ecological momentary assessment has been recommended in the
      management of chronic pain. Smartphone apps might be a useful tool for that
      purpose. This goal of this study was to develop and test a multidimensional
      smartphone app for adults with chronic pain. A multidisciplinary team developed
      the app content after a series of meetings, considering clinical guidelines for
      pain measurement. The content included pain intensity and interference, fatigue,
      mood, perceived health status, activity level, side effects of the medication,
      use of rescue medication, and pain-related sychological constructs
      (catastrophizing, acceptance, fear, and coping). METHODS: Thirty-eight
      participants (21 to 59 y) used the app, called Pain Monitor, twice a day during
      30 consecutive days. Patients completed a set of well-established measures at the
      beginning and end of the study via paper-and-pencil. Weekly phone assessments
      were also made for pain intensity, pain interference, fatigue, and mood. RESULTS:
      Construct validity was revealed by moderate-to-strong correlations between app
      content and traditional measures. Feasibility was supported by high compliance
      (between 70% and 82%) and high acceptability and ease of use. Both side effects
      of the medication and use of rescue medication were found to be useful tools to
      guide treatment. DISCUSSION: The new assessment protocol in the app allows for an
      easy and rapid multidimensional assessment of chronic pain patients.

PMID- 29659376
TI  - When a Child Dies Unexpectedly: No Truth Be Told.
AB  - Sudden death of a child beyond infancy is a rare event. We report a child who
      presented to the emergency care system with asystole and the caregiver's report
      of an asthma attack as the preceding event. After unsuccessful attempts at
      resuscitation, an autopsy was performed by the medical examiner. Despite only
      scattered bruises with no clear-cut signs of abuse, aortic rupture and spinal
      fractures were found. This case highlights the crucial role of the medical
      examiner in evaluating sudden childhood death, even in the setting of underlying
      illness.

PMID- 29659377
TI  - Anorectal complications in patients with haematological malignancies.
AB  - BACKGROUND: Anorectal complications are common in patients with haematological
      malignancies. OBJECTIVES: The objectives are to characterize anorectal
      complications in these patients, identify risk factors and shed light on
      treatment, morbidity and mortality rates. PATIENTS AND METHODS: A retrospective,
      observational study that included 83 inpatients with haematological malignancies
      and proctological symptoms from January 2010 to September 2015 was conducted.
      Clinical outcomes were obtained through a detailed review of medical records.
      RESULTS: The median age was 56 years, and 52 (62.7%) patients were men. Fifty-six
      (67.5%) patients had nonseptic anorectal complications and 27 (32.5%) patients
      had septic anorectal complications. RISKS FACTORS: Patients with septic anorectal
      complications were more commonly male, older, and had lower absolute neutrophil
      counts, but the differences were not statistically significant (P=0.79, 0.67 and
      0.89, respectively). In positive blood cultures [23/70 (32.9%)], Enterococcus
      faecium, Klebsiella pneumonia, and Escherichia coli were the most common isolated
      agents. TREATMENT: In nonseptic anorectal complications, conservative
      treatments/minor proctological procedures were adopted, and patients with septic
      anorectal complications were treated with antibiotics+/-major proctological
      procedures and/or surgical drainage/debridement. RESULTS OF TREATMENT: Forty
      eight (85.7%) patients in the nonseptic complications group improved compared
      with 23 (85.2%) patients in the septic complications group. The overall mortality
      rate was 2.4% (n=2), with one (1.2%) death related to perianal sepsis.
      CONCLUSION: Enterococcus spp. were more commonly identified in this study and can
      be increasing in this specific population. In contrast to other reports, we did
      not identify an association between septic anorectal complications and possible
      risk factors such as male sex, younger age or a low absolute neutrophil count.
      Most patients had nonseptic anorectal complications. A major proctological
      procedure/surgical debridement should always be applied in septic complications,
      which have better prognoses now than in the past.

PMID- 29659378
TI  - Osteoimmunology: Effects of Standard Orthopaedic Interventions on Inflammatory
      Response and Early Fracture Healing.
AB  - Achieving fracture union is highly dependent on the initial inflammatory phase of
      fracture healing, which is influenced by both the local and systemic inflammatory
      environments. The rapidly emerging field of osteoimmunology involves the study of
      the interactions between the immune system and the skeletal system. Recent
      research has advanced the current state of knowledge regarding the effects of the
      surrounding soft-tissue injury, fracture hematoma, and the method of fracture
      fixation on the inflammatory phase of fracture healing. Acute systemic
      inflammation, as seen in patients with polytrauma, and chronic systemic
      inflammation, as seen in patients with diabetes or rheumatoid arthritis, affects
      the inflammatory phase of fracture healing. The use of NSAIDs can influence early
      fracture healing. Understanding the effects of standard orthopaedic interventions
      on the local and systemic inflammatory responses and early fracture healing is
      important for optimizing fracture union.

PMID- 29659379
TI  - Bony Reconstruction of the Anterior Glenoid Rim.
AB  - Recurrent anterior shoulder instability is associated with glenohumeral bone
      loss. Glenoid deficiency compromises the concavity-compression mechanism. Medial
      Hill-Sachs lesions can result in an off-track humeral position. Anterior glenoid
      reconstruction or augmentation prevents recurrence by addressing the
      pathomechanics. In Bristow and Latarjet procedures, the coracoid process is
      harvested for conjoint tendon transfer, capsular reinforcement, and glenoid rim
      restoration. Complications and the nonanatomic nature of the procedure have
      spurred research on graft sources. The iliac crest is preferred for autogenous
      structural grafts. Tricortical, bicortical, and J-bone grafts have shown
      promising results despite the historical association of Eden-Hybinette procedures
      with early degenerative joint disease. Allogeneic osteochondral grafts may
      minimize the risk of arthropathy and donor site morbidity. Tibial plafond and
      glenoid allografts more closely match the native glenoid geometry and restore the
      articular chondral environment, compared with conventional grafts. Graft
      availability, cost, risk of disease transmission, and low chondrocyte viability
      have slowed the acceptance of osteochondral allografts.

PMID- 29659380
TI  - Effect of pioglitazone and simvastatin in lipopolysaccharide-induced
      amyloidogenesis and cognitive impairment in mice: possible role of glutamatergic
      pathway and oxidative stress.
AB  - Neuroinflammation and beta-amyloid (Abeta) deposition in the brain are well known
      characteristics of neurodegeneration. Diabetes and hypercholesterolemia are the
      main risk factors leading to memory loss and cognitive impairment. Recently, it
      was found that statins and thiazolidinediones have promising anti-inflammatory
      and neuroprotective effects that could delay neurodegeneration and neuronal loss
      in diabetic and hypercholesterolemic patients. The aim of the present study was
      to investigate the protective effect of simvastatin, pioglitazone, and their
      combination in lipopolysaccharide (LPS)-induced neuroinflammation and
      amyloidogenesis. Mice were divided into five groups: group 1 received 0.9%
      saline, group 2 received LPS (0.8 mg/kg in saline), group 3 received LPS (0.8 mgl
      kg)+simvastatin (5 mg/kg in saline), group 4 received LPS (0.8
      mg/kg)+pioglitazone (20 mg/kg in saline), group 5 receiving LPS (0.8
      mg/kg)+simvastatin (5 mg/kg)+pioglitazone (20 mg/kg). Y-maze and novel object
      recognition were used to assess the spatial and nonspatial behavioral changes.
      Nitric oxide levels and glutamate levels were measured to elucidate the anti
      glutamatergic and anti-inflammatory effects of the tested drugs.
      Immunohistochemistry was performed to detect the presence of Abeta1-42 in the
      mice brain. LPS impaired memory, and increased Abeta deposition, nitric oxide,
      and glutamate brain levels. Both drugs produced a significant improvement in all
      parameters. We conclude that simvastatin and pioglitazone may have a protective
      effect against cognitive impairment induced by LPS, through targeting the
      glutamatergic and inflammatory pathways, especially in patients having
      hypercholesterolemia and diabetes.

PMID- 29659382
TI  - Tenofovir Versus Entecavir for the Treatment of Acute-on-Chronic Liver Failure
      due to Reactivation of Chronic Hepatitis B With Genotypes B and C.
AB  - BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) can be triggered by
      reactivation of chronic hepatitis B (CHB). Tenofovir disoproxil fumarate (TDF)
      and entecavir (ETV) are now the most potent antiviral agents for CHB. This study
      aimed to compare the short-term safety and efficacy of TDF with ETV in the
      treatment of ACLF due to reactivation of CHB [hepatitis B virus (HBV)-ACLF].
      PATIENTS AND METHODS: In total, 67 consecutive patients with HBV-ACLF were
      divided into TDF group (n=32) receiving daily TDF (300 mg/d) and ETV group (n=35)
      receiving daily ETV (0.5 mg/d). They were prospectively followed-up and the
      primary endpoint was overall survival at 3 months. RESULTS: At 2 weeks, the TDF
      group had significantly higher HBV-DNA reduction (P=0.003), lower HBV-DNA level
      (P=0.001), higher rate of HBV-DNA undetectbility (P=0.007), lower Child-Turcotte
      Pugh (CTP; P=0.003), and model for end-stage liver disease (P=0.002) scores than
      the ETV group. At 3 months, HBV-DNA was undetectable in all survived patients;
      CTP (P=0.970) and model for end-stage liver disease (P=0.192) scores were
      comparable between the 2 groups, but markedly lower than at baseline (P<0.01);
      the TDF group had significantly higher cumulative survival rate than the ETV
      group (P=0.025). The white blood cell count (hazard ratio, 2.726; 95% confidence
      interval, 2.691-7.897; P=0.000), and HBV-DNA reduction (hazard ratio, 0.266; 95%
      confidence interval, 0.033-0.629; P=0.013) at 2 weeks were independent predictors
      for mortality. Both drugs were well tolerated. CONCLUSIONS: The short-term
      efficacy of TDF was superior to ETV for the treatment of HBV-ACLF. The white
      blood cell count and HBV-DNA reduction at 2 weeks were independent predictors for
      mortality at 3 months.

PMID- 29659383
TI  - Prostate-Specific Membrane Antigen-Negative Metastases-A Potential Pitfall in
      Prostate-Specific Membrane Antigen PET.
AB  - Ga-PSMA-11 PET/CT was performed in a 74-year-old man because of biochemical
      recurrence of prostate cancer following radiation therapy of the prostate gland
      24 months earlier. Besides focal nuclide accumulation in the prostate gland
      suggestive of local recurrence, PET scan revealed no further pathologic uptake.
      However, CT showed multiple pulmonic nodules suggestive of metastases.
      Thoracotomy and pathologic examination revealed the nodules to be prostate cancer
      metastasis. Furthermore, immunohistochemical staining with PSMA antibodies
      demonstrated a virtual lack of PSMA expression. This case demonstrates the
      possibility of PSMA-negative metastases of prostate cancer an important pitfall
      that should be known to physicians interpreting PSMA PET.

PMID- 29659384
TI  - Tumor-Induced Osteomalacia Caused by a Parotid Basal Cell Adenoma Detected by
      68Ga-DOTANOC PET/CT.
AB  - Tumor-induced osteomalacia is a rare paraneoplastic syndrome, usually caused by
      small benign mesenchymal tumors. The tumors most arise within the extremities,
      whereas occurrence within the parotid gland is quite rare. A 54-year-old woman
      who presented with bone pain and muscle weakness for 2 years was clinically
      suspected of having tumor-induced osteomalacia. A Ga-DOTANOC PET/CT was performed
      for localization of the causative tumor. The images demonstrated intense
      radiotracer accumulation in a soft tissue nodule in deep lobe of the right
      parotid gland. Subsequent surgical resection and pathologic analysis confirmed
      the diagnosis of parotid basal cell adenoma.

PMID- 29659381
TI  - Methodological Aspects for Preclinical Evaluation of Gadolinium Presence in Brain
      Tissue: Critical Appraisal and Suggestions for Harmonization-A Joint Initiative.
AB  - Gadolinium (Gd)-based contrast agents (GBCAs) are pharmaceuticals that have been
      approved for 30 years and used daily in millions of patients worldwide. Their
      clinical benefits are indisputable. Recently, unexpected long-term presence of Gd
      in the brain has been reported by numerous retrospective clinical studies and
      confirmed in preclinical models particularly after linear GBCA (L-GBCA) compared
      with macrocyclic GBCA (M-GBCA). Even if no clinical consequences of Gd presence
      in brain tissue has been demonstrated so far, in-depth investigations on
      potential toxicological consequences and the fate of Gd in the body remain
      crucial to potentially adapt the clinical use of GBCAs, as done during the
      nephrogenic systemic fibrosis crisis. Preclinical models are instrumental in the
      understanding of the mechanism of action as well as the potential safety
      consequences. However, such models may be associated with risks of biases, often
      related to the protocol design. Selection of adequate terminology is also
      crucial. This review of the literature intends to summarize and critically
      discuss the main methodological aspects for accurate design and translational
      character of preclinical studies.

PMID- 29659385
TI  - Lateral Recumbent or Prone Positioning for PET of the Urinary Bladder.
AB  - Evaluation of the urinary bladder on PET with F-FDG is hampered by accumulation
      of activity in the urinary bladder due to physiological excretion of F-FDG in
      urine. We present 2 examples that demonstrate the utility of delayed scanning in
      lateral recumbent or prone position to improve evaluation of the bladder by
      differentiating between active bladder wall lesions and intraluminal activity.
      Changing the body position from a supine to a lateral recumbent or prone position
      can result in migration of intraluminal activity due to gravitational force,
      whereas F-FDG uptake in bladder wall lesions will show no migration.

PMID- 29659386
TI  - Added Value of SPECT/CT in the Evaluation of Sacral Fracture in Patients With
      Lung Cancer.
AB  - We describe the sacral fractures from 2 lung cancer patients that were confirmed
      by SPECT/CT. The utilization of SPECT/CT in lung cancer patients can help
      characterizing the nature of sacral lesions on planar bone scintigraphy.

PMID- 29659388
TI  - Imaging of Metastatic Epithelioid Trophoblastic Tumor With 18F-FDG PET/CT.
AB  - Epithelioid trophoblastic tumors are exceptionally rare malignant forms of
      gestational trophoblastic neoplasia arising from the placenta. We present here a
      case of a 33-year-old woman with an epithelioid trophoblastic tumor with
      metastatic disease to the lungs that was initially thought to represent cervical
      carcinoma. After appropriate diagnosis and treatment, the tumor responded to
      therapy and was in remission. The cancer recurred 5 years later with new lung
      metastases. F-FDG PET/CT was used for initial tumor staging, to evaluate
      treatment response, and to help detect the recurrence.

PMID- 29659387
TI  - Bilateral Adrenal Hyperplasia Due to Adrenocorticotropic Hormone-Secreting
      Esthesioneuroblastoma on FDG PET and 111In-Pentetreotide Scintigraphy.
AB  - A 53-year-old woman with metastatic esthesioneuroblastoma was referred for FDG
      PET/CT imaging. FDG PET/CT showed symmetrical uptake in bilaterally enlarged
      adrenal glands, in addition to abnormal uptake in bone and lymph node metastases.
      In-pentetreotide scintigraphy was further performed and revealed the lack of
      adrenal uptake. The patient's serum adrenocorticotropic hormone (ACTH) level was
      extremely high, suggesting that hyperplastic condition in the adrenal glands due
      to ACTH stimulation from the metastatic esthesioneuroblastoma was responsible for
      increased FDG uptake. The combination of FDG PET and In-pentetreotide
      scintigraphy was useful for the pathophysiological evaluation of ACTH-secreting
      esthesioneuroblastoma.

PMID- 29659389
TI  - FDG-PET/CT Focal Uptake on an Ocular Prosthesis.
AB  - We present a case of an unexpected focally increased radiotracer uptake in an
      artificial eye in an FDG-PET/CT scan that was performed on a woman with a history
      of choroidal melanoma. It is crucial to know the type of prosthesis used and the
      timing of replacement for a correct interpretation of the findings. Recently, an
      FDG PET/CT was proposed to monitor the vascularity of the prosthesis instead of
      gadolinium MRI or of Tc bone scintigraphy.

PMID- 29659390
TI  - Combined [18F]-Fluoroethylcholine PET/CT and 99mTc-Macroaggregated Albumin
      SPECT/CT Predict Survival in Patients With Intermediate-Stage Hepatocellular
      Carcinoma.
AB  - AIM: The aim of this study was to retrospectively analyze the prognostic value of
      combined Tc-macroaggregated albumin (MAA) SPECT/CT and [F]-fluoroethylcholine
      (FEC) PET/CT before radioembolization for survival of patients with intermediate
      stage hepatocellular carcinoma. METHODS: Twenty-four patients with known
      hepatocellular carcinoma Barcelona Clinic Liver Cancer stage B were eligible for
      this analysis. All patients were scheduled for radioembolization and received a
      pretherapeutic [F]FEC PET/CT scan as well as Tc-MAA SPECT/CT for hepatopulmonary
      shunting. Laboratory and semiquantitative PET parameters and morphologic and
      metabolic (intersection) volumes of MAA and FEC were evaluated. Spearman
      correlation with overall survival, receiver operating curve analyses, univariate
      and multivariate Cox regression, and Kaplan-Meier-analysis was applied. RESULTS:
      All patients (5 female/19 male) are deceased within the observational period.
      Median survival was 395 days (+/-51 days; range, 23-1122 days). The percentage of
      hypervascularized metabolically active tumor volume (vascularized tumor ratio;
      defined as high MAA and FEC uptake) correlated significantly with survival.
      Vascularized tumor ratio was a significant predictor in univariate and
      multivariate analyses (P = 0.026; hazard ratio, 11.65; 95% confidence interval,
      1.62-83.73; P = 0.015). Statistical significance was not reached by all other
      variables in multivariate analysis. Receiver operating curve analysis for 1-year
      survival revealed an area under the curve of 0.77 (P = 0.024) for vascularized
      tumor ratio. At a cutoff value of 9%, sensitivity, specificity, and positive and
      negative prediction were 83%, 67%, and 71% and 80% (P = 0.036). Patients with a
      higher tumor vascularization had a median survival of 274 +/- 80 versus 585 +/-
      284 days (P = 0.015). CONCLUSIONS: Hepatocellular carcinoma with high
      vascularization in metabolic active areas as assessed by combined FEC PET/CT and
      Tc-MAA SPECT/CT represents an unfavorable subgroup with reduced overall survival
      after radioembolization.

PMID- 29659391
TI  - Pediatric Patient With Cerebral Metastasis From Papillary Thyroid Cancer.
AB  - Brain metastasis from papillary thyroid carcinoma is uncommon. Concurrent
      cerebral and pulmonary metastases from papillary thyroid carcinoma is rare,
      especially in pediatric patients. We report a case of a brain metastasis revealed
      on post-therapy I scan in a 12 year old girl with thyroid cancer who also had
      diffuse pulmonary metastases which were partially responsive to sequential I
      therapy.

PMID- 29659392
TI  - Pedunculated Hepatocellular Carcinoma Mimicking Right Adrenal Tumor on FDG
      PET/CT.
AB  - Pedunculated hepatocellular carcinoma is an unusual form of hepatocellular
      carcinoma protruding from the liver with or without a pedicle. We present a case
      of pedunculated hepatocellular carcinoma misdiagnosed as right adrenal tumor on
      MRI and FDG PET/CT. Intraoperative exploration revealed the mass was attached to
      the liver, but the right adrenal gland was intact. Laparoscopic biopsy revealed
      poorly differentiated hepatocellular carcinoma. This case indicates it may be
      difficult to diagnose pedunculated hepatocellular carcinoma because it is hard to
      define its origin on imaging. Elevated alpha-fetoprotein level and a history of
      viral hepatitis may be helpful for the diagnosis.

PMID- 29659393
TI  - Unexpected Vesicoureteral Reflux Into a Nonfunctioning Transplant Kidney on Renal
      Scintigraphy.
AB  - Vesicoureteral reflux after renal transplantation is associated with increase
      risk of urinary tract infections, renal scarring, and graft failure. We describe
      a case of a 46-year-old woman with 2 transplant kidneys, one functioning and
      another nonfunctioning, presenting with pelvic pain after a bilateral
      periureteral bulking procedure. Diuretic renography was performed to exclude
      iatrogenic ureteral obstruction. This showed a normally functioning transplant
      kidney without obstruction and subsequent vesicoureteral reflux into the
      collecting system of the nonfunctioning transplant kidney. This inadvertent
      indirect nuclear cystogram illustrates an unusual imaging presentation of a
      common disease process requiring further treatment.

PMID- 29659394
TI  - A Bizarre Bone Scan of Fibrodysplasia Ossificans Progressiva.
AB  - A 27-year-old woman had progressive bony ankylosis over both hands since she was
      5 years old. Bony ankylosing over the peripheral joints and spine slowly
      progressed, and scoliosis surgery was performed at age 14. Recently, she
      developed difficulty walking, changing position, and opening her mouth. A
      neurologist was consulted and ruled out the suspicion of narcolepsy. Chest CT
      showed ankylosing spondylitis. A bone scan showed a bizarre pattern with
      radiouptake to the left maxilla, bilateral sacroiliac joints, left middle third
      femur, and soft tissue uptake over bilateral arms, legs, and pelvis. Regional
      radiograph suggested fibrodysplasia ossificans progressiva.

PMID- 29659395
TI  - Loss of PSMA Expression in Non-neuroendocrine Dedifferentiated Acinar Prostate
      Cancer.
AB  - The introduction of tracers targeting the prostate-specific membrane antigen
      (PSMA) has revolutionized PET imaging of acinar prostate adenocarcinoma. In
      general, an increasing PSMA expression is assumed with increasing
      dedifferentiation. Whereas loss of PSMA expression has been reported in case of
      neuroendocrine dedifferentiation, we present a patient with acinar prostate
      adenocarcinoma with a loss of PSMA expression after chemotherapy on PET/CT and in
      histological and immunohistochemical analyses. All tissue samples indicated the
      retention of acinar features but no expression of neuroendocrine markers (NSE,
      synaptophysin, chromogranin, and CD56), corresponding to nonelevated serum NSE.

PMID- 29659396
TI  - Sequential Sentinel Node Scintigraphy With Planar and SPECT/CT Images Revealed
      Contralateral Drainage From Ipsilateral Breast Tumor Relapse in a Patient With
      Bilateral Breast Cancer.
AB  - Radio-guided sentinel node (SN) biopsy is routinely performed in patients with
      early breast cancer. However, repeated SN scintigraphy in ipsilateral breast
      tumor relapse (IBTR) often shows extra-axillary drainage, including contralateral
      axilla. A patient diagnosed with bilateral breast cancer, of which one was IBTR,
      was studied by sequential radio-guided SN mapping, radiocolloid injection to an
      IBTR breast and scanning, and then radiocolloid injection to the other breast and
      scanning. This revealed the lymphatic flow from the IBTR breast to the
      contralateral axilla. Sequential method may help to depict contralateral axillary
      lymphatic flow from an IBTR breast in patients with bilateral breast cancer.

PMID- 29659397
TI  - Scintigraphic and Sonographic Findings of Subcapsular Cortical Necrosis in a
      Transplanted Kidney.
AB  - Renal transplant scintigraphy, performed in a 23-year-old man who had renal graft
      from a living donor, showed nearly normal perfusion and moderately low function
      of the graft. But the margins of the graft were blurred, and it was interestingly
      appearing enlarged late in the study. Ultrasound demonstrated a hypoechoic rim
      surrounding the whole kidney. Biopsy revealed necrosis besides normal cortical
      tissue. Necrosis was thought to be limited to the subcapsular cortical area. It
      should be considered that these scintigraphic findings could be due to greatly
      reduced and delayed perfusion of edematous subcapsular necrotic area of the graft
      even in normal perfusion images.

PMID- 29659398
TI  - Mixed Epithelial and Stromal Tumor of the Kidney Mimicking Malignancy on 18F-FDG
      PET/CT in a Patient With Breast Cancer.
AB  - Mixed epithelial and stromal tumor of the kidney (MESTK) is a rare renal tumor
      composed of solid and cystic components. Mixed epithelial and stromal tumor of
      the kidney has no pathognomonic imaging feature. It is difficult to distinguish
      MESTK from other cystic renal neoplasms using current radiological methods. We
      report a rare case of MESTK that was diagnosed in a 46-year-old woman with breast
      cancer. F-FDG PET/CT and contrast-enhanced CT features of MESTK are presented,
      which could potentially provide useful information in the differential diagnoses
      of cystic renal neoplasms.

PMID- 29659399
TI  - Top-Down Systematic Approach to Interpretation of FDG-PET for Dementia.
AB  - Dementia is an important cause of morbidity and mortality worldwide and
      encompasses a very heterogenous group of disease processes. Positron emission
      tomography (PET) of the brain using fluorodeoxyglucose (FDG) is a useful modality
      for differentiating types of dementia. Because FDG does not bind to pathologic
      proteins, FDG-PET requires that the reader recognize characteristic patterns of
      glucose hypometabolism to identify pathology. These patterns have been documented
      in the literature for both primary neurodegenerative disorders and secondary
      causes of dementia. This article presents an algorithm for organizing these
      findings and systematically applying them to interpret FDG-PET brain imaging for
      dementia.

PMID- 29659400
TI  - Peliosis Hepatis Simulating Metastatic Liver Disease on FDG PET/CT.
AB  - A 20-year-old man with gastrointestinal symptoms and weight loss underwent FDG
      PET/CT, which revealed multiple hypermetabolic hepatic lesions concerning for
      metastatic liver disease. The outcome of liver biopsy was consistent with the
      diagnosis of peliosis hepatis which is a rare benign disease characterized by
      multiple blood-filled cystic spaces in the hepatic parenchyma. The findings of
      peliosis on FDG PET/CT are not well reported in the literature. These interesting
      images emphasize the importance of including peliosis hepatis in the differential
      diagnosis of multiple hypermetabolic hepatic lesions on FDG PET/CT, which could
      simulate malignancy.

PMID- 29659402
TI  - Features of Irradiated Skeletal Muscle on Mohs Frozen Section Examination.

PMID- 29659401
TI  - Effects of Different Footwear Properties and Surface Instability on Neuromuscular
      Activity and Kinematics During Jumping.
AB  - Lesinski, M, Prieske, O, Borde, R, Beurskens, R, and Granacher, U. Effects of
      different footwear properties and surface instability on neuromuscular activity
      and kinematics during jumping. J Strength Cond Res XX(X): 000-000, 2018-The
      purpose of this study was to examine sex-specific effects of different footwear
      properties vs. barefoot condition during the performance of drop jumps (DJs) on
      stable and unstable surfaces on measures of jump performance, electromyographic
      (EMG) activity, and knee joint kinematics. Drop jump performance, EMG activity of
      lower-extremity muscles, as well as sagittal and frontal knee joint kinematics
      were tested in 28 healthy male (n = 14) and female (n = 14) physically active
      sports science students (23 +/- 2 years) during the performance of DJs on stable
      and unstable surfaces using different footwear properties (elastic vs. minimal
      shoes) vs. barefoot condition. Analysis revealed a significantly lower jump
      height and performance index (Delta7-12%; p < 0.001; 2.22 <= d = 2.90) during DJs
      on unstable compared with stable surfaces. This was accompanied by lower
      thigh/shank muscle activities (Delta11-28%; p < 0.05; 0.99 <= d = 2.16) and knee
      flexion angles (Delta5-8%; p < 0.05; 1.02 <= d = 2.09). Furthermore, knee valgus
      angles during DJs were significantly lower when wearing shoes compared with
      barefoot condition (Delta22-32%; p < 0.01; 1.38 <= d = 3.31). Sex-specific
      analyses indicated higher knee flexion angles in females compared with males
      during DJs, irrespective of the examined surface and footwear conditions
      (Delta29%; p < 0.05; d = 0.92). Finally, hardly any significant footwear-surface
      interactions were detected. Our findings revealed that surface instability had an
      impact on DJ performance, thigh/shank muscle activity, and knee joint kinematics.
      In addition, the single factors "footwear" and "sex" modulated knee joint
      kinematics during DJs. However, hardly any significant interaction effects were
      found. Thus, additional footwear-related effects can be neglected when performing
      DJs during training on different surfaces.

PMID- 29659403
TI  - Dermatologic Surgery and Reconstruction Photograph Booklet as a Tool to Improve
      Informed Consent Before Skin Surgery.
AB  - BACKGROUND: Skin surgery is a high-risk area of litigation and tools to improve
      consent are welcomed. OBJECTIVE: This project aimed to strengthen the consenting
      process for dermatological surgery by introducing a photograph booklet. MATERIALS
      AND METHODS: The authors designed a booklet containing skin surgery images.
      Patients attending surgery completed an anonymous questionnaire immediately after
      their procedures before the booklet introduction (Group 1). The questionnaire was
      then repeated (Group 2) with the introduction of the photograph booklet during
      consent. The authors looked for changes in the following: understanding of
      procedure, scar, and postoperative care as well as addressing of patients'
      concerns using a subjective scale of 1 to 5 (1 = poor, 2 = fair, 3 = okay, 4 =
      good, and 5 = great). RESULTS: Results indicated greater patient satisfaction
      among patients in Group 2 who had been shown relevant surgical images compared
      with Group 1, with improvements from ratings of 3 and 4 on the scale to 5. The
      difference in the 2 groups for the highest ratings of 5/5 was significant (p <
      .05) for understanding of procedure and resulting scars. CONCLUSION: The use of
      photograph booklets containing simple and relevant images to support the consent
      process for dermatologic surgery improves patients' understanding, expectations,
      and experience of skin surgery.

PMID- 29659404
TI  - Prospective Cohort Study Investigating Changes in Body Image, Quality of Life,
      and Self-Esteem Following Minimally Invasive Cosmetic Procedures.
AB  - BACKGROUND: Minimally invasive cosmetic injectable procedures are increasingly
      common. However, a few studies have investigated changes in psychosocial
      functioning following these treatments. OBJECTIVE: To assess changes in body
      image, quality of life, and self-esteem following cosmetic injectable treatment
      with soft tissue fillers and neuromodulators. METHODS: Open, prospective study of
      75 patients undergoing cosmetic injectable procedures for facial aging to
      evaluate changes in psychosocial functioning within 6 weeks of treatment. Outcome
      measures included the Derriford appearance scale (DAS-24), body image quality of
      life inventory (BIQLI), and the Rosenberg self-esteem scale. RESULTS: Body image
      dissatisfaction, as assessed by the DAS-24, improved significantly 6 weeks after
      the treatment. Body image quality of life, as assessed by the BIQLI, improved,
      but the change did not reach statistical significance. Self-esteem was unchanged
      after the treatment. CONCLUSION: Minimally invasive cosmetic injectable
      procedures were associated with reductions in body image dissatisfaction. Future
      research, using recently developed cosmetic surgery-specific instruments, may
      provide further insight into the psychosocial benefits of minimally invasive
      procedures.

PMID- 29659405
TI  - The Safety and Efficacy of Treatment With a 1,927-nm Diode Laser With and Without
      Topical Hydroquinone for Facial Hyperpigmentation and Melasma in Darker Skin
      Types.
AB  - BACKGROUND: The nonablative, fractional, 1,927-nm diode laser is theoretically a
      safe and effective treatment for hyperpigmentation and melasma in darker skin and
      may potentiate topical cosmeceutical delivery. OBJECTIVE: To evaluate the use of
      a nonablative, fractional, 1,927-nm diode laser with and without topical 2%
      hydroquinone (HQ) cream for moderate-to-severe facial hyperpigmentation in
      Fitzpatrick skin Types III-V. METHODS: Forty adults underwent 4 laser treatments
      at 2-week intervals and were randomized to daily application of 2% HQ cream or
      moisturizer. Follow-ups were conducted 4 and 12 weeks after the final laser
      treatment. RESULTS: Hydroquinone and moisturizer groups demonstrated Mottled
      Pigmentation Area and Severity Index improvements of approximately 50% at post
      treatment Weeks 4 and 12. Blinded investigator-assessed hyperpigmentation and
      photodamage improved significantly for both the groups at post-treatment Weeks 4
      and 12. Subject satisfaction improved significantly in both the groups by post
      treatment Week 4. Although investigator-rated Global Aesthetic Improvement Scale
      scores were significantly better in the HQ group at post-treatment Week 12,
      satisfaction was higher among those using moisturizer. No adverse events were
      noted. CONCLUSION: The nonablative, fractional, 1,927-nm diode laser produced
      significant improvement in hyperpigmentation in Fitzpatrick skin Types III-V by 4
      weeks, with maintenance of results at 12 weeks after treatment even without HQ.

PMID- 29659406
TI  - Topical Botulinum Toxin Type A Liposomal Cream for Primary Axillary
      Hyperhidrosis: A Double-Blind, Randomized, Split-Site, Vehicle-Controlled Study.
AB  - BACKGROUND: Despite its effectiveness in treating primary axillary hyperhidrosis
      (PAH), topical botulinum toxin type A (BTX-A) is highly resistant to transdermal
      absorption. Topical BTX-A liposomal cream is recommended as a novel, noninvasive
      modality to enhance skin penetration. OBJECTIVE: To evaluate the efficacy and
      safety of topical BTX-A liposomal cream in comparison with liposomal vehicle
      cream alone in the treatment of PAH. MATERIALS AND METHODS: A prospective,
      randomized, double-blinded, split-site study was conducted in 20 subjects, aged
      18 to 50 years, all of whom had symmetrical axillary sweating with Hyperhidrosis
      Disease Severity Scale scores between 2 to 4. All subjects were double-blinded to
      treatment regimens and randomly given 2 bottles, one containing topical BTX-A
      liposomal cream and one containing the vehicle cream without BTX-A, to be applied
      consistently to the same axilla nightly for 7 consecutive days. Clinical
      improvement and adverse reactions were evaluated at every follow-up visit.
      RESULTS: Axillary skin treated with topical BTX-A demonstrated superior sweat
      reduction and patient satisfaction to vehicle cream-treated axillary skin, with
      clinical and statistical significance, at baseline, weeks 2, 4, 6, and 8 of
      follow-up, without adverse effects. CONCLUSION: Topical BTX-A liposomal cream
      pharmaceutically enhances drug delivery, is painless, cost-effective, and overall
      an innovative treatment of PAH.

PMID- 29659407
TI  - Trends in Dermatologic Surgery: Results of the American Society for Dermatologic
      Surgery Procedure and Consumer Surveys.

PMID- 29659408
TI  - Pseudohalo Basal Cell Carcinoma.

PMID- 29659409
TI  - Liposarcoma Preoperatively Diagnosed as Lipoma: 10-Year Experience at a Single
      Institution.
AB  - BACKGROUND: On rare occasions, a lesion preoperatively diagnosed as a lipoma is
      ultimately diagnosed as a liposarcoma. It is important to differentiate
      liposarcomas from lipomas preoperatively. OBJECTIVE: To examine characteristic
      features of liposarcomas preoperatively diagnosed as lipomas. METHODS: Patients
      (n = 637) who underwent resection of tumors preoperatively diagnosed as lipomas
      from January 2006 to October 2016 were retrospectively reviewed. RESULTS: Based
      on pathological examination, 8 of 637 lesions were diagnosed as liposarcomas
      postoperatively. All the liposarcomas were well-differentiated liposarcomas. The
      rate of male patients was higher (87.5% vs 38.9%) and the size of tumors was
      larger (8.75 vs 4.64 cm) in these cases than in accurately diagnosed lipoma
      cases. On imaging, nonfatty septa were more frequently observed (71.4% vs 20.0%)
      and were thicker (2.22 vs 1.33 mm) than in true lipoma cases. CONCLUSION: If the
      patient with a lipomatous tumor is male and the tumor is large, we should
      consider the possibility of it being a liposarcoma. A thick internal septum in
      the image findings is a good predictor of malignancy.

PMID- 29659410
TI  - In Vivo Degradation of Crosslinked Hyaluronic Acid Fillers by Exogenous
      Hyaluronidases.
AB  - BACKGROUND: An advantage of hyaluronic acid (HA)-based fillers is reversibility.
      OBJECTIVE: To evaluate the ability of 2 hyaluronidases to degrade 3 HA-based
      fillers using a novel in vivo model. MATERIALS AND METHODS: Rats were injected
      with 3 HA fillers (HYC-24L+, VYC-20L, and RES-L) to create a projecting bolus.
      After 4 days, recombinant human hyaluronidase (HX) or ovine hyaluronidase (VIT)
      was administered at (1) varying doses (5 U, 10 U, or 30 U per 0.1 mL filler) or
      (2) different dilutions (10 U diluted 3-fold). The impact of tissue integration
      was assessed by administering 10 U/0.1 mL filler 4 weeks after filler injection.
      Three-dimensional images quantified projection loss over 72 hours. RESULTS:
      Complete loss of projection was achieved for all fillers with the highest HX and
      VIT doses; lower doses achieved less degradation. No difference in degradation
      was observed between HYC-24L+ and VYC-20L using HX or VIT. RES-L was slightly
      more degraded with 10 U VIT but not with 10 U HX. Enzyme dilution resulted in
      less degradation. Tissue integration did not impact the degree of degradation.
      CONCLUSION: This model incorporates the biological system while controlling
      variables including filler depth and volume and location of hyaluronidase
      delivery. Hyaluronic acid filler degradation by exogenous hyaluronidase was not
      hindered by differences among fillers.

PMID- 29659411
TI  - ACCURACY AND PRECISION OF INTRAVITREAL INJECTIONS OF ANTI-VASCULAR ENDOTHELIAL
      GROWTH FACTOR AGENTS IN REAL LIFE: What Is Actually in the Syringe?
AB  - PURPOSE: To evaluate the accuracy and precision of anti-vascular endothelial
      growth factor volume delivery by intravitreal injections in the clinical setup.
      METHODS: Volume output was measured in 669 intravitreal injections administered
      to patients, calculated from the difference in syringe weight before and after
      expelling the drug. Three groups were included: prefilled bevacizumab 1.0 mL
      syringe (Group 1, n = 432), pre-filled ranibizumab in a small-volume syringe with
      low dead-space plunger design (Group 2, n = 125), and aflibercept drawn and
      injected using a 1.0-mL syringe (Group 3, n = 112). Accuracy was analyzed by mean
      absolute percentage error, and precision by coefficient of variation. RESULTS:
      Volume outputs in all 3 groups were significantly different from the target of 50
      MUL (P < 0.0001 for all), and mean absolute percentage error values were 12.25%
      +/- 5.92% in Group 1, 13.60% +/- 8.75% in Group 2, and 24.69% +/- 14.84% in Group
      3. No difference was found between groups 1 and 2, but both were significantly
      more accurate than Group 3 (P < 0.0001 for both). CONCLUSION: The current
      practices used for intravitreal injections are highly variable, with overdelivery
      of the anti-vascular endothelial growth factor drugs measured in most cases, but
      underdelivery in 16.3% of injections. Use of a prefilled syringe was associated
      with improved accuracy, and low dead-space plunger design may improve precision.

PMID- 29659412
TI  - PHOTODYNAMIC THERAPY AS PRIMARY TREATMENT FOR SMALL CHOROIDAL MELANOMA.
AB  - PURPOSE: To report outcomes of photodynamic therapy (PDT) as primary treatment
      for small amelanotic choroidal melanoma. METHODS: Retrospective interventional
      case series of 12 patients with small choroidal melanoma treated with standard
      fluence PDT (83 seconds; 50 J/cm) using verteporfin. OUTCOME MEASURES: Tumor
      regression, subretinal fluid resolution, best-corrected visual acuity, and PDT
      complications. RESULTS: There were 12 eyes with melanoma, demonstrating
      amelanotic (10 [83%]) or lightly pigmented (n = 2, 17%) appearance. The mean
      tumor thickness was 2.7 mm (median, 2.8; range 1.8-3.7 mm). After PDT, mean
      follow-up was 56 months (median, 53; range, 14-91). Outcomes revealed complete
      tumor regression after 1 session (n = 3, 25%), 2 sessions (n = 3, 25%), and 3
      sessions (n = 2, 17%) of PDT, reduced to mean thickness of 2.1 mm (median, 2.0;
      range 1.2-3.4 mm). Tumors that failed to regress (n = 4, 33%) were further
      controlled with transpupillary thermotherapy (n = 1) or plaque brachytherapy (n =
      3). Subretinal fluid, present in six eyes, demonstrated resolution (n = 5) or
      progression (n = 1), and one tumor developed new subretinal fluid after PDT (n =
      1). Visual outcome was stable (n = 11 eyes) or improved (n = 1). Photodynamic
      therapy complications included local retina pigment epithelium atrophy at the
      site of treatment in 3 (25%) eyes, with no effect on macular or optic nerve
      function. CONCLUSION: Primary PDT resulted in complete tumor regression of small
      amelanotic choroidal melanoma in 67% at mean 5 years, with no major effect on
      visual acuity.

PMID- 29659413
TI  - A Smartphone Application to Reduce the Time to Automated External Defibrillator
      Delivery After a Witnessed Out-of-Hospital Cardiac Arrest: A Randomized
      Simulation-Based Study.
AB  - INTRODUCTION: We developed a new smartphone application to deliver an automated
      external defibrillator (AED) to out-of-hospital cardiac arrest scene. The aim of
      this study was to evaluate whether an AED could be delivered earlier with or
      without an application in a simulated randomized controlled trial. METHODS:
      Participants, who were asked to work as bystanders, were randomly assigned to
      either an application group or control group and were asked to bring an AED in
      both groups. The bystanders in the application group sent a signal notification
      using the application to two responders, who were stationed within 200 meters of
      the arrest scene, to carry an AED. The primary outcome was the AED delivery time
      by either the bystander or his/her responder. RESULTS: In total, 61 bystanders
      were eligible and randomized to either the application group (32) or the control
      group (29). The 52 with time data were available and analyzed. The AED delivery
      time by either the bystander or his/her responder was significantly shorter in
      the application group than in the control group [133.6 (44.4) seconds vs. 202.2
      (122.2) seconds, P = 0.01]. CONCLUSIONS: In this simulation-based trial, AED
      delivery time was shortened by our newly developed smartphone application for the
      bystander to ask nearby responders to find and bring an AED to the cardiac arrest
      scene (UMIN-Clinical Trials Registry 000016506).

PMID- 29659414
TI  - Repeated Audiometry After Bacterial Meningitis: Consequences for Future
      Management.
AB  - OBJECTIVE: Sensorineural hearing loss is a common sequela of bacterial
      meningitis. The objective of this study is to delineate the incidence and course
      of hearing loss after bacterial meningitis. STUDY DESIGN: Retrospective cohort
      study. SETTING: Tertiary referral center. PATIENTS: Data of 655 patients who
      suffered from bacterial meningitis between 1985 and 2015 were analyzed.
      INTERVENTIONS: None. MAIN OUTCOME MEASUREMENTS: Availability of audiometric data,
      incidence of hearing loss, and onset and course of hearing loss. RESULTS: In this
      cohort the incidence of hearing loss (>25 dB) was 28% (95% confidence interval 23
      34%). The incidence of profound hearing loss (>80 dB) was 13% (95% confidence
      interval 10-18%). Normal hearing at the first assessment after treatment for
      meningitis remained stable over time in all these patients. In 19 of the 28
      patients with diagnosed hearing loss, the hearing level remained stable over
      time. Hearing improved in six patients and deteriorated in two patients. One
      patient showed a fluctuating unilateral hearing loss. CONCLUSION: Audiological
      tests in patients with bacterial meningitis, especially children, should be
      started as soon as possible after the acute phase is over. As we found no
      deterioration of initial normal hearing after bacterial meningitis, repeated
      audiometry seems indicated only for those with diagnosed hearing loss at first
      assessment.

PMID- 29659415
TI  - Functional Status Change Among Children With Extracorporeal Membrane Oxygenation
      to Support Cardiopulmonary Resuscitation in a Pediatric Cardiac ICU: A Single
      Institution Report.
AB  - OBJECTIVES: The purpose of this study is to describe the functional status of
      survivors from extracorporeal cardiopulmonary resuscitation instituted during in
      hospital cardiac arrest using the Functional Status Scale. We aimed to determine
      risk factors leading to the development of new morbidity and unfavorable
      functional outcomes. DESIGN: This was a single-center retrospective chart review
      abstracting patient characteristics/demographic data, duration of cardiopulmonary
      resuscitation, duration of extracorporeal membrane oxygenation support, as well
      as maximum lactate levels within 2 hours before and after extracorporeal
      cardiopulmonary resuscitation. Cardiac arrest was defined as the administration
      of chest compressions for a nonperfusing cardiac rhythm. Extracorporeal
      cardiopulmonary resuscitation was defined by instituting extracorporeal membrane
      oxygenation during active chest compressions. Functional Status Scale scores were
      calculated at admission and on hospital discharge for patients who survived.
      SETTING: Patients admitted in the pediatric cardiac ICU at C.S. Mott Children's
      Hospital from January 1, 2005, to December 31, 2015. PATIENTS: Children less than
      18 years who underwent extracorporeal cardiopulmonary resuscitation.
      INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: Of 608
      extracorporeal membrane oxygenation events during the study period, 80 were
      extracorporeal cardiopulmonary resuscitation (14%). There were 40 female patients
      (50%). Median age was 40 days (interquartile range, 9-342 d). Survival to
      hospital discharge was 48% (38/80). Median Functional Status Scale score at
      admission was 6 (interquartile range, 6-6) and at hospital discharge 9
      (interquartile range, 8-11). Out of 38 survivors, 19 (50%) had a change of
      Functional Status Scale score greater than or equal to 3, that is consistent with
      new morbidity, and 26 (68%) had favorable functional outcomes with a change in
      Functional Status Scale score of less than 5. CONCLUSIONS: This is the first
      extracorporeal cardiopulmonary resuscitation report to examine changes in
      Functional Status Scale from admission (baseline) to discharge as a measure of
      overall functional outcome. Half of surviving patients (19/38) had new morbidity,
      while 68% (26/38) had favorable outcomes. Lactate levels, duration of
      cardiopulmonary resuscitation, and duration of extracorporeal membrane
      oxygenation were not found to be risk factors for the development of new
      morbidity and poor functional outcomes. Functional Status Scale may be used as a
      metric to monitor improvement of extracorporeal cardiopulmonary resuscitation
      outcomes and help guide research initiatives to decrease morbidity in this
      patient population.

PMID- 29659416
TI  - A Pilot Randomized Controlled Trial of an Intervention to Promote Psychological
      Well-Being in Critically Ill Children: Soothing Through Touch, Reading, and
      Music.
AB  - OBJECTIVES: To examine the feasibility and acceptability of a PICU Soothing
      intervention using touch, reading, and music. DESIGN: Nonblinded, pilot
      randomized controlled trial. SETTING: The PICU and medical-surgical wards of one
      Canadian pediatric hospital. PATIENTS: Twenty PICU patients age 2-14 years old
      and their parents, randomized to an intervention group (n = 10) or control group
      (n = 10). INTERVENTION: PICU Soothing consisted of: 1) parental comforting (touch
      and reading), followed by 2) a quiet period with music via soft headbands,
      administered once daily throughout hospitalization. MEASUREMENTS AND MAIN
      RESULTS: Acceptability and feasibility of the intervention and methods were
      assessed via participation rates, observation, measurement completion rates,
      semistructured interviews, and telephone calls. Psychological well-being was
      assessed using measures of distress, sleep, and child and parent anxiety in the
      PICU, on the wards and 3 months post discharge. Forty-four percent of parents
      agreed to participate. Seventy percent and 100% of intervention group parents
      responded positively to comforting and music, respectively. Most intervention
      group parents (70%) and all nurses felt children responded positively. All nurses
      found the intervention acceptable and feasible. Measurement completion rates
      ranged from 70% to 100%. Pilot data suggested lower intervention group child and
      parent anxiety after transfer to hospital wards. CONCLUSIONS: PICU Soothing is
      acceptable and feasible to conduct. Results support the implementation of a full
      scale randomized controlled trial to evaluate intervention effectiveness.

PMID- 29659417
TI  - Circulating microRNA as Emerging Biomarkers of Exercise.
AB  - An interest has recently emerged in the role of circulating microRNAs (c-miRNAs)
      as posttranscriptional regulators, intercellular communicators and, especially,
      as potential biomarkers of the systemic response to acute exercise and training.
      We propose that, with the limited, heterogeneous, and mainly descriptive
      information currently available, c-miRNAs do not provide a reliable biomarker of
      exercise in healthy or diseased individuals.

PMID- 29659418
TI  - Enhancing Lesbian, Gay, Bisexual, and Transgender Cultural Competence in a
      Midwestern Primary Care Clinic Setting.
AB  - The process of initiating lesbian, gay, bisexual, and transgender (LGBT) cultural
      competencies and educational interventions developed to increase staff knowledge
      on LGBT culture and health issues is discussed, including a computer-based module
      and panel discussion. The module intervention showed a statistically significant
      increase (p = .033) of staff LGBT knowledge from pretest to posttest scores. An
      evaluation after the panel discussion showed that 72% of staff indicated they
      were more prepared for LGBT patient care.

PMID- 29659419
TI  - Primary Tracheal Carcinoma.

PMID- 29659421
TI  - Air-splinting Maneuver During Flexible Bronchoscopy: A Cross-sectional Study.
AB  - BACKGROUND: Magazine's maneuver was developed for ease of insertion of the
      flexible bronchoscope, on encountering a closed lumen at the nasopharynx
      oropharynx junction. The purposes of this study were to find the frequency of
      occurrence of such luminal closures and to compare the efficacy of Magazine's
      maneuver, with other variations of the maneuver, in improving visualization of
      the upper airway. MATERIALS AND METHODS: Patients aged 18 years and above who
      were undergoing flexible bronchoscopy were included, and their demographic and
      clinical data were noted. The bronchoscope was inserted using the transnasal
      approach, and, at the junction of nasopharynx with oropharynx, the patency of the
      lumen between the soft palate and the posterior pharyngeal wall was recorded. The
      subjects were instructed to perform 4 variations of the maneuver. Observations at
      each variation were recorded as lumen open or closed; if the lumen was open, the
      size was noted as small or large and whether it closed during expiration.
      RESULTS: Among 443 subjects, obstruction at the nasopharynx-oropharynx junction
      was observed, at baseline, in 105 (23.7%); whereas 338 (76.3%) had an open lumen.
      An open lumen was observed during nose and mouth breathing in 294 (66.4%)
      subjects, and, when head-tilt chin-lift was added to it, it was observed in 303
      (68.4%). During Magazine's maneuver the lumen remained open in all 443 (100%)
      subjects. Half of the subjects (n=8) with body mass index >30 and one-third
      (n=29) above 65 years of age had luminal closure at baseline. CONCLUSION:
      Magazine's maneuver opens up the obstruction at the nasopharynx-oropharynx
      junction, whereas mouth and nose breathing mostly fails to do so. Adding head
      tilt chin-lift to either of the 2 breathing techniques does not provide any
      additional benefit.

PMID- 29659420
TI  - Needle-based Optical Coherence Tomography to Guide Transbronchial Lymph Node
      Biopsy.
AB  - BACKGROUND: Transbronchial needle aspiration (TBNA), often used to sample lymph
      nodes for lung cancer staging, is subject to sampling error even when performed
      with endobronchial ultrasound. Optical coherence tomography (OCT) is a high
      resolution imaging modality that rapidly generates helical cross-sectional
      images. We aim to determine if needle-based OCT can provide microstructural
      information in lymph nodes that may be used to guide TBNA, and improve sampling
      error. METHODS: We performed ex vivo needle-based OCT on thoracic lymph nodes
      from patients with and without known lung cancer. OCT imaging features were
      compared against matched histology. RESULTS: OCT imaging was performed in 26
      thoracic lymph nodes, including 6 lymph nodes containing metastatic carcinoma.
      OCT visualized lymphoid follicles, adipose tissue, pigment-laden histiocytes, and
      blood vessels. OCT features of metastatic carcinoma were distinct from benign
      lymph nodes, with microarchitectural features that reflected the morphology of
      the carcinoma subtype. OCT was also able to distinguish lymph node from adjacent
      airway wall. CONCLUSIONS: Our results demonstrate that OCT provides critical
      microstructural information that may be useful to guide TBNA lymph node sampling,
      as a complement to endobronchial ultrasound. In vivo studies are needed to
      further evaluate the clinical utility of OCT in thoracic lymph node assessment.

PMID- 29659422
TI  - Bending of an Aspirated Pin During Rigid Bronchoscopy: Safeguards and Pitfalls.
AB  - BACKGROUND: Pin aspiration is a common problem in Muslim countries, where many
      women wear veils (hijab). This condition is usually treated using either a rigid
      or a flexible bronchoscope, and yet occasionally requires surgical approach. Pin
      bending may be necessary to extract impacted pins during the therapeutic rigid
      bronchoscopy. METHODS: Medical records of patients who had pins extracted with a
      bending technique during the period from January 2012 to December 2016 in 1
      institution were analyzed. Information on intraoperative and postoperative
      complications was collected. RESULTS: Between 2012 and 2016, 315 rigid
      bronchoscopies were performed for pin extraction; in 38 cases, bending of the pin
      was required for the extraction because they were in a position that did not
      allow simple extraction. The procedure was successful in cases and there were no
      major complications. CONCLUSION: The extraction of visible, distally located or
      impacted pins can be safely performed by experienced bronchoscopists using the
      bending technique. Some safeguards and pitfalls must be noted to ensure maximum
      safety.

PMID- 29659423
TI  - Safety and Efficacy of Oki Stenting Used to Treat Obstructions in the Right
      Mainstem Bronchus.
AB  - BACKGROUND: Silicone stenting has been used to palliatively manage respiratory
      symptoms in patients with airway stenoses. Oki and Saka recently developed stents
      that can be used to manage stenoses around the carina between the bronchus to the
      right upper lobe and the bronchus intermedius (termed the primary right carina).
      The aim of this study was to assess the efficacy and safety of Oki stenting used
      to treat airway stenosis around the primary right carina. METHODS: We included 5
      patients with airway stenoses. All Oki stenting procedures were performed with
      the patients under general anesthesia using either rigid or flexible
      bronchoscopy. RESULTS: Oki stents were successfully placed in all 5 patients, and
      the dyspnea index improved in all. Modified Oki stenting was performed at the
      anastomotic site of 1 patient who had undergone sleeve resection. Four patients
      had airway obstructions caused by malignant disease. No serious procedural or
      early complication was noted. One patient died of liver insufficiency, and
      another with a malignancy died from cranial metastasis of the primary tumor.
      CONCLUSION: Oki stenting of the primary right carina is safe, efficient, and
      acceptable when used for palliative management of airway obstruction, even after
      sleeve resection; in the latter case, some procedural modifications are required.

PMID- 29659424
TI  - Utility of Magnetic Resonance Imaging for Predicting Severity of Sciatic Nerve
      Injury.
AB  - OBJECTIVE: This study aimed to investigate the diagnostic accuracy of magnetic
      resonance (MR) imaging for categorizing sciatic peripheral nerve injury (PNI) as
      high-grade (Sunderland grades IV-V) or low-grade (Sunderland grades I-III) PNI.
      METHODS: In this institutional review board-approved, Health Insurance
      Portability and Accountability Act-compliant retrospective study, consecutive MR
      imaging of the pelvis and thighs, performed for the evaluation of traumatic
      sciatic neuropathy, was reviewed for sciatic nerve signal intensity, size,
      architectural distortion, bulbous enlargement, perineural fibrosis,
      discontinuity, and muscle denervation changes. Clinical data, electrodiagnostic
      testing, and surgical history were used to determine PNI grade (high, low).
      Descriptive and diagnostic performance statistics were applied. RESULTS: Of 24
      patients, there were 12 high-grade and 12 low-grade PNI. There was no significant
      difference in signal intensity or size between high-grade and low-grade PNI (1.3
      +/- 0.5 cm vs 0.9 +/- 0.3 cm, P = 0.09). The sensitivity and specificity for the
      presence of individual features in predicting high-grade injury were 83% and 67%
      for architectural distortion, 58% and 75% for bulbous enlargement, 50% and 83%
      for perineural fibrosis, 25% and 100% for discontinuity, and 67% and 75% for
      skeletal muscle denervation changes, respectively. Overall, the sensitivity and
      specificity of MR imaging for categorizing sciatic PNI as high grade was 75% and
      83%, respectively. CONCLUSIONS: The MR characterization of PNI severity remains
      challenging. Useful features indicative of high-grade PNI include bulbous
      enlargement, perineural fibrosis, muscle denervation changes, and nerve
      discontinuity.

PMID- 29659425
TI  - Dual-Energy Computed Tomography in Patients With Small Hepatocellular Carcinoma:
      Utility of Noise-Reduced Monoenergetic Images for the Evaluation of Washout and
      Image Quality in the Equilibrium Phase.
AB  - PURPOSE: This study aimed to evaluate the utility of virtual monoenergetic images
      for detecting washout of small (<=2 cm) hepatocellular carcinoma (HCC) in the
      equilibrium phase. METHODS: We performed 120-kVp-equivalent linear-blended (M120)
      and monoenergetic reconstructions from 40 to 90 keV by standard (40, 50, 60, 70,
      80, 90) and novel noise-reduced (nMERA: 40+, 50+, 60+, 70+, 80+, 90+)
      monoenergetic reconstruction algorithms. Image quality and tumor visibility of
      delayed washout of HCCs in the equilibrium phase were compared between standard
      monoenergetic reconstruction algorithm and nMERA by objective and subjective
      analyses. RESULTS: Contrast-to-noise ratio of the tumor at 40+ was the highest,
      whereas the score of tumor visibility peaked at 50+. The score of overall image
      quality at 40+ was significantly lower than those on all other image series, and
      the image quality among other image series were not significantly different.
      CONCLUSIONS: Virtual monoenergetic image reconstructed with nMERA 50+ was most
      appropriate to detect washout of small HCCs.

PMID- 29659426
TI  - Evaluation of Virtual Monoenergetic Images on Pulmonary Vasculature Using the
      Dual-Layer Detector-Based Spectral Computed Tomography.
AB  - OBJECTIVE: To evaluate the ability of retrospectively generated virtual
      monoenergetic images (VMIs) from the detector-based spectral computed tomography
      (SDCT) to augment pulmonary artery enhancement in CT and if iodine map can
      predict the optimal monoenergetic level. METHODS: The study included 79 patients
      with contrast-enhanced chest CT scans on an SDCT scanner. Conventional 120-kVp
      images and VMI from 40 to 80 keV were generated. Attenuation, noise, signal-to
      noise ratio (SNR), and contrast-to-noise ratio (CNR) were measured at 7 different
      locations in the pulmonary arterial system. The iodine concentration (in
      milligrams per milliliter) was calculated using the iodine-density images. The
      overall image quality was subjectively graded on a 5-point scale, with 1 being
      the worst and 5 the best. Fifty-four patients with suboptimal pulmonary
      enhancement (<200 Hounsfield units [HU]) were then identified. From the VMIs, an
      ideal set was chosen that maintained mean vascular attenuation greater than 200
      HU while maintaining at least diagnostically acceptable quality (ie, IQ score
      >=3). At this ideal energy level, quantitative and qualitative parameters were
      compared with the standard 120-kVp polyenergetic study. Average iodine
      concentrations were correlated with the optimal keV levels used for salvaging
      suboptimal studies. RESULTS: The mean attenuation of all the measured pulmonary
      arterial regions in the suboptimal cases was 136.1 +/- 18.1 HU in conventional
      120-kVp images. Attenuations of the VMIs at 40, 50, and 60 keV were significantly
      higher than conventional images measuring 357.5 +/- 19.5, 243.6 +/- 16.7, and
      176.6 +/- 15.0 HU, respectively (P < 0.001). Similar results were seen with SNR
      and CNR. In total, 50 studies can be salvaged, with 50 keV being the optimal
      energy for 21, 60 keV optimal for 17, and 40 keV optimal for 12 studies. At the
      optimal energy level, there were improvements of attenuation, SNR, and CNR by
      71%, 63%, and 137% compared with conventional images. There was a positive
      correlation between iodine value and optimal reconstruction energy with a linear
      equation y = 5.9539x + 27.434 and R = 0.8093. CONCLUSIONS: Suboptimal enhanced
      pulmonary arterial CT studies can be salvaged using low-energy VMI generated from
      the SDCT scanner. There were significant improvements of attenuation, SNR, and
      CNR at the optimal monoenergetic level.

PMID- 29659427
TI  - Opportunistic Bone Density Measurement on Abdomen and Pelvis Computed Tomography
      to Predict Fracture Risk in Women Aged 50 to 64 Years Without Osteoporosis Risk
      Factors.
AB  - OBJECTIVE: The aim of this study is to evaluate opportunistic vertebral bone
      density measurement in abdominal and pelvic computed tomography (CT) to predict
      future osteoporotic fracture in women aged 50 to 64 years without known
      osteoporosis risk factors. METHODS: Consecutive female patients 50 to 64 years
      old without osteoporosis risk factors with 2 CT examinations more than 10 years
      apart were included. Vertebral height and bone density in each vertebra from T10
      to L5 were measured. Vertebral fractures were diagnosed on CT preformed 10 years
      after the original CT and through online medical records. RESULTS: Thirty (15%)
      of 199 patients developed osteoporotic fracture. Bone density was lower in
      patients who developed fractures compared with those who did not (P < 0.05).
      Development of osteoporotic fracture of any grade was predicted for patients
      having bone density less than 180 HU at L4 with sensitivity of 90% (95%
      confidence interval, 74%-97%) and specificity of 43% (95% confidence interval,
      34%-50%). CONCLUSIONS: Opportunistic bone density screening can identify women at
      elevated risk of developing fractures within 10 years.

PMID- 29659428
TI  - Rotator Cuff Tear Morphologic Parameters at Magnetic Resonance Imaging:
      Relationship With Muscle Atrophy and Fatty Infiltration and Patient-Reported
      Function and Health-Related Quality of Life.
AB  - OBJECTIVE: The aim of this study was to determine the relationship between
      rotator cuff tear (RCT) morphologic parameters and muscle atrophy and fatty
      infiltration, and patient-reported outcome measures, in patients with symptomatic
      full-thickness RCT. METHODS: Rotator cuff tear location, length, width,
      thickness, and musculotendinous junction position were assessed in 57 magnetic
      resonance imaging scans and correlated to the outcome measures using multivariate
      regression analysis. RESULTS: Supraspinatus tendon tear length (odds ratio [OR],
      2.218; 95% confidence interval [CI], 1.460-3.370), supraspinatus musculotendinous
      junction position (OR, 2.037; 95% CI, 1.322-3.137), and infraspinatus tendon tear
      width (OR, 2.371; 95% CI, 1.218-4.615) were identified as the strongest
      determinants of supraspinatus muscle atrophy, supraspinatus muscle fatty
      infiltration, and infraspinatus muscle fatty infiltration, respectively.
      CONCLUSIONS: The extent of supraspinatus tendon and musculotendinous junction
      retraction influences the development of supraspinatus muscle atrophy and fatty
      infiltration, whereas the extent of infraspinatus tendon tear width influences
      the development of infraspinatus muscle fatty infiltration. Morphologic
      parameters defining RCT at magnetic resonance imaging did not correlate with
      clinical shoulder function scores.

PMID- 29659429
TI  - Spectral Detector Computed Tomography Pulmonary Angiography: Improved Diagnostic
      Assessment and Automated Estimation of Window Settings Angiography of Pulmonary
      Arteries From Novel Spectral Detector Computed Tomography Provides Improved Image
      Quality if Settings are Adjusted.
AB  - OBJECTIVE: This study aimed to evaluate image quality (IQ) of virtual
      monoenergetic images (VMIs) from novel spectral detector computed tomography
      angiography of the pulmonary arteries and to identify appropriate window settings
      for each kiloelectron volt level. MATERIALS: Forty consecutive patients were
      included in this institutional review board-approved, Health Insurance
      Portability and Accountability Act-compliant study.Signal- and contrast-to-noise
      ratios were calculated within the pulmonary trunk, and pulmonary/lobar/segmental
      arteries were calculated. The IQ and diagnostic certainty were rated by 2
      radiologists on 5-point scales. In addition, they recorded appropriate window
      settings (center/width) that were linearly modeled against attenuation within the
      pulmonary trunk to generate generable results. RESULTS: Signal- and contrast-to
      noise ratios, IQ, and diagnostic certainty are significantly increased in low
      kiloelectron volt VMIs (<=60 keV). Interrater agreement was excellent (K = 0.89).
      We developed 2 linear models (R: 0.91-0.97 and R: 0.43-0.91, respectively, P <=
      0.01), that suggest appropriate window settings. CONCLUSIONS: The VMIs from
      spectral detector computed tomography improve objective and subjective IQ in
      angiography of the pulmonary arteries, if window settings are adjusted; they can
      be automatically estimated using reported linear models.

PMID- 29659430
TI  - Risk Factors Associated With Incomplete Colonoscopy Based on the Analysis of
      Computed Tomographic Colonography Findings.
AB  - OBJECTIVE: This study aimed to identify the computed tomographic colonography
      (CTC) findings of incomplete colonoscopy compared with those of complete
      colonoscopy. METHODS: The clinical data and CTC imaging data from January 2004 to
      December 2012 were retrospectively obtained at 2 different institutions and
      reviewed by the central review system. A total of 71 patients who underwent both
      videocolonoscopy and CTC were included in this study. The CTC findings and
      clinical data were evaluated for the completeness of colonoscopy. RESULTS: In the
      CTC analysis, differences in total colon length, abdominal circumference, and
      sigmoid colon diameter were statistically significant between both groups (P <
      0.05). Body mass index (BMI) and height were identified as significant clinical
      factors influencing the completeness of colonoscopy. In multiple logistic
      regression tests, only BMI and sigmoid colon diameter were independent factors (P
      < 0.05). CONCLUSIONS: High BMI larger diameter of sigmoid colon was associated
      with incomplete colonoscopy based on CTC.

PMID- 29659431
TI  - Preliminary Study on Molecular Subtypes of Breast Cancer Based on Magnetic
      Resonance Imaging Texture Analysis.
AB  - OBJECTIVE: The aim of the study was to investigate the molecular subtypes of
      breast cancer based on the texture features derived from magnetic resonance
      images (MRIs). METHODS: One hundred seven patients with preoperative confirmed
      breast cancer were recruited. One hundred eight breast lesions were divided into
      4 subtypes according to the status of estrogen receptor, progesterone receptor,
      human epidermal growth factor receptor type 2, and Ki67. Fisher discriminant
      analysis was performed on the texture features that extracted from the enhanced
      high-resolution T1-weighted images and diffusion weighted images to establish the
      classification model of molecular subtypes. RESULTS: The differentiation
      accuracies of Fisher discriminant analysis on the enhanced high-resolution T1
      weighted images were 82.8% and 86.4% for 1.5T and 3.0T imaging. Fisher
      discriminant analysis on diffusion weighted imaging texture features were
      achieved with a classification ability of 73.4% and 88.6%. The combined
      discriminant results for 2 kinds magnetic resonance images were 95.0%, 97.7% in
      1.5T and 3.0T imaging, respectively. CONCLUSIONS: The fine results indicated a
      promising approach to predict the molecular subtypes of breast cancer.

PMID- 29659432
TI  - Orbital Inflammatory Syndrome Secondary to Flea Bite.
AB  - A 34-year-old previously healthy Hispanic male presented to the emergency room
      complaining of progressive left upper eyelid swelling and pain for more than 2
      weeks. He was previously diagnosed and treated for a "pink eye" but failed to
      improve. He reported a previous "bug bite" around the left lateral canthus a few
      weeks prior to admission. Computer tomography orbit with contrast showed left
      exophthalmos, an enhancing left lacrimal gland and orbital inflammatory signs
      suggestive of possible intraorbital abscess. Intravenous antibiotics did not
      improve his symptoms. Surgical debridement showed no abscess but inflamed soft
      tissues and lacrimal gland. Intravenous steroids failed to improve his symptoms.
      On postoperative day 3, the patient reported that an insect had "jumped" out from
      his left orbit. Identification of the specimen proved to be a mature flea. Biopsy
      of the lacrimal gland showed degranulation of eosinophils and foreign body
      material consistent with probable insect leg parts.

PMID- 29659433
TI  - Congenital Accessory Palpebral Fissure and Eyelid in a Newborn: A Case Report.
AB  - The occurrence of an accessory palpebral fissure and eyelid is an extremely rare
      phenomenon. An isolated accessory palpebral fissure and eyelid have been reported
      only twice in the literature, and in one case as an extension of Delleman
      syndrome, or oculocerebrocutaneous syndrome. The authors report a case of a full
      term newborn who presented with an accessory palpebral fissure and eyelid
      associated with microcornea, skin polyps and tags, cutis dysplasia, and
      hypoplasia of the corpus callosum with an otherwise normal systemic workup and
      negative genetic screening. Detailed surgical management and histopathological
      analysis of the accessory findings are also described.

PMID- 29659434
TI  - Similarity in Bilateral Isolated Internal Orbital Fractures.
AB  - PURPOSE: In evaluating patients sustaining bilateral isolated internal orbital
      fractures, the authors have observed both similar fracture locations and also
      similar expansion of orbital volumes. In this study, we aim to investigate if
      there is a propensity for the 2 orbits to fracture in symmetrically similar
      patterns when sustaining similar trauma. METHODS: A retrospective chart review
      was performed studying all cases at our institution of bilateral isolated
      internal orbital fractures involving the medial wall and/or the floor at the time
      of presentation. The similarity of the bilateral fracture locations was evaluated
      using the Fisher's exact test. The bilateral expanded orbital volumes were
      analyzed using the Wilcoxon signed-rank test to assess for orbital volume
      similarity. RESULTS: Twenty-four patients with bilateral internal orbital
      fractures were analyzed for fracture location similarity. Seventeen patients
      (70.8%) had 100% concordance in the orbital subregion fractured, and the
      association between the right and the left orbital fracture subregion locations
      was statistically significant (P < 0.0001). Fifteen patients were analyzed for
      orbital volume similarity. The average orbital cavity volume was 31.2 +/- 3.8 cm
      on the right and 32.0 +/- 3.7 cm on the left. There was a statistically
      significant difference between right and left orbital cavity volumes (P =
      0.0026). CONCLUSIONS: The data from this study suggest that an individual who
      suffers isolated bilateral internal orbital fractures has a statistically
      significant similarity in the location of their orbital fractures. However, there
      does not appear to be statistically significant similarity in the expansion of
      the orbital volumes in these patients.

PMID- 29659435
TI  - Frontalis Muscle Flap Versus Maximal Anterior Levator Resection as First Option
      for Patients With Severe Congenital Ptosis.
AB  - PURPOSE: To compare 2 surgical techniques (frontalis flap versus maximal anterior
      levator resection) as first surgical options for the treatment of congenital
      ptosis with poor levator function in patients younger than 2 years of age with a
      follow up of 10 years. METHODS: A retrospective study of 58 patients (71 eyelids)
      with severe ptosis and poor levator function who underwent frontalis muscle flap
      (FMF = 47) or maximal anterior levator resection (ALR = 24) for correction of
      their ptosis. Eyelid measurements were taken at baseline, 1, 5, and 10 years
      after surgery. The presence of complications, need for reoperations, and
      palpebral contour were evaluated. RESULTS: Most patients in both groups required
      only one surgical procedure with a stable average margin-reflex distance 1 over
      the 10-year follow-up period in both groups, with no statistically significant
      difference between the 2 techniques in achieving an adequate palpebral height
      after one single procedure. Eleven eyelids treated with FMF (23%) and 12 treated
      with ALR (50%) needed a reoperation, with a statistically significant difference
      between the 2 techniques. Five ALR patients (21%) and 6 FMF patients (13%) had
      alterations of eyelid contour. Pop-eyelid and eyelash ptosis were observed in 8%
      of patients operated with FMF. CONCLUSION: Good functional and aesthetic results
      were obtained with both surgical techniques. FMF required fewer reoperations
      compared with maximal ALR, offering a better long-term result without residual
      ptosis.

PMID- 29659436
TI  - A Novel Technique of Ultrasound-Guided Selective Mandibular Nerve Block With a
      Lateral Pterygoid Plate Approach: A Cadaveric Study.
AB  - BACKGROUND AND OBJECTIVES: We aimed to describe a novel technique of ultrasound
      guided selective mandibular nerve block with a lateral pterygoid plate (LPP)
      approach and to assess its feasibility and accuracy in a soft cadaver model.
      METHODS: Ten soft cadavers were studied. A curved array ultrasound transducer was
      applied over 1 side of the face of the cadaver, in an open-mouth position. The
      transducer was placed transversely below the zygomatic arch and tilted in the
      caudal-to-cranial direction to identify the boundary of the LPP. The needle was
      inserted in-plane, in an anterior-to-posterior direction, into the posterior
      border of the uppermost part of the LPP, and 3 mL of methylene blue was injected.
      RESULTS: Mandibular nerve block was successfully performed in all 10 cadavers
      using an LPP approach under ultrasound guidance. The mandibular nerve and its
      branches were seen to be stained with methylene blue in all cadaveric specimens.
      No accidental injection into the facial nerve or maxillary artery was observed.
      CONCLUSIONS: This cadaveric study suggests that this novel technique, using an
      LPP approach under ultrasound guidance, is helpful for selective mandibular nerve
      block, with high accuracy and feasibility. Further studies are required to
      establish its safety and efficacy for clinical application. CLINICAL TRIAL
      REGISTRATION: This study was registered at the Thai Clinical Trials Registry
      (ClinicalTrials.in.th), identifier TCTR20160601004.

PMID- 29659437
TI  - The Impact of Spinal Needle Selection on Postdural Puncture Headache: A Meta
      Analysis and Metaregression of Randomized Studies.
AB  - BACKGROUND AND OBJECTIVES: Potentially broadened indications for spinal
      anesthesia require increased understanding of the risk factors and prevention
      measures associated with postdural puncture headache (PDPH). This review is
      designed to examine the association between spinal needle characteristics and
      incidence of PDPH. METHODS: Meta-analysis and metaregression was performed on
      randomized controlled trials to determine the effect of needle design and gauge
      on the incidence of PDPH after controlling for patient confounders such as age,
      sex, and year of publication. RESULTS: Fifty-seven randomized controlled trials
      (n = 16416) were included in our analysis, of which 32 compared pencil-point
      design with cutting-needle design and 25 compared individual gauges of similar
      design. Pencil-point design was associated with a statistically significant
      reduction in incidence of PDPH (risk ratio, 0.41; 95% confidence interval, 0.31
      0.54; P < 0.001; I = 29%) compared with cutting needles among studies that
      assessed both design types. Subgroup analysis among obstetric and nonobstetric
      procedures yielded similar results. After adjustment for significant covariates,
      metaregression analysis among all 57 included trials revealed a significant
      correlation between needle gauge and rate of PDPH among cutting needles (slope = 
      2.65, P < 0.001), but not pencil-point needles (slope = -0.01, P = 0.819).
      CONCLUSIONS: Pencil-point needles are associated with significantly lower
      incidence of PDPH compared with the cutting-needle design. Whereas a significant
      relationship was noted between needle gauge and PDPH for cutting-needle design, a
      similar association was not shown for pencil-point needles. Providers may
      consider selection of larger-caliber pencil-point needle to maximize technical
      proficiency without expensing increased rates of PDPH.

PMID- 29659438
TI  - Selective Suprascapular and Axillary Nerve Block Versus Interscalene Plexus Block
      for Pain Control After Arthroscopic Shoulder Surgery: A Noninferiority Randomized
      Parallel-Controlled Clinical Trial.
AB  - BACKGROUND AND OBJECTIVES: This randomized trial aimed to assess if a combined
      suprascapular-axillary nerve block (SSB) is noninferior (margin = 1.3 on a 0- to
      10-point scale) to interscalene block (ISB) in treating pain after arthroscopic
      shoulder surgery. Secondary end points included opioid consumption, dyspnea,
      discomfort associated with muscle weakness, and patient satisfaction. METHODS:
      One hundred patients undergoing arthroscopic shoulder surgery were randomized to
      receive ultrasound-guided ISB (n = 50) or SSB (n = 50). Pain intensity at rest,
      dyspnea, and discomfort were recorded upon arrival in the recovery room,
      discharge to the ward, and at 4, 8, and 24 hours after surgery. Piritramide
      consumption was recorded for the first 24 hours. Patient satisfaction was
      assessed on the second postoperative day. RESULTS: During the first 4 hours after
      surgery, the difference in mean pain score between SSB and ISB was higher than
      2.5 (+/-0.8). The difference gradually decreased to 1.1 (+/-1.0) at 8 hours
      before resulting in noninferiority during the night and at 24 hours. Piritramide
      consumption was significantly higher in the SSB group in the first 8 hours. The
      incidence of dyspnea and discomfort was higher after ISB. Treatment satisfaction
      was similar in both groups. CONCLUSIONS: Suprascapular-axillary nerve block is
      inferior to ISB in terms of analgesia and opioid requirement in the immediate
      period after arthroscopic shoulder surgery but is associated with a lower
      incidence of dyspnea and discomfort. The difference in pain and opioid
      consumption gradually decreases as the blocks wear off in order to reach similar
      pain scores during the first postoperative night and at 24 hours. CLINICAL TRIAL
      REGISTRATION: This study was registered at ClinicalTrials.gov, identifier
      NCT02415088.

PMID- 29659439
TI  - Clotting-Factor Concentrations 5 Days After Discontinuation of Warfarin.
AB  - BACKGROUND: The American Society of Regional Anesthesia and Pain Medicine
      guidelines recommend discontinuation of warfarin and an international normalized
      ratio (INR) of 1.2 or less before a neuraxial injection. The European and
      Scandinavian guidelines accept an INR of 1.4 or less. We evaluated INR and levels
      of clotting factors (CFs) II, VII, IX, and X 5 days after discontinuation of
      warfarin. METHODS: Patients who discontinued warfarin for 5 days and had an INR
      of 1.4 or less had activities of factors II, VII, IX, and X measured. The primary
      outcome was the frequency of subjects with CF activities of less than 40%.
      RESULTS: Twenty-three patients were studied; 21 (91%) had an INR of 1.2 or less.
      In these 21 patients, the median (interquartile range) activities of factors II,
      VII, IX, and X were 66% (52%-80%), 114% (95%-132%), 101% (84%-121%), and 55% (46%
      63%), respectively. Ninety-five percent (99% confidence interval, 69%-99%) had CF
      activities of greater than 40%. The patient who did not CF activities greater
      than 40% had end-stage renal disease. Two subjects had an INR of greater than
      1.2; the activities of factor II, VII, IX, and X were 37% and 46%, 89% and 105%,
      66% and 78%, and 20% and 36%, respectively. Neither patient had CF activities of
      greater than 40%. CONCLUSIONS: Based on 40% activity of CFs, patients with INRs
      of 1.2 or less can be considered to have adequate CFs to undergo neuraxial
      injections. The number of patients with an INR of 1.3 and 1.4 is too small to
      make conclusions.

PMID- 29659440
TI  - Measurement Properties of the Functional Rating Index: A Systematic Review and
      Meta-analysis.
AB  - STUDY DESIGN: A systematic review and meta-analysis. OBJECTIVE: To assess the
      measurement properties of the Functional Rating Index (FRI) and determine whether
      its measurement properties are comparable with other region-specific
      questionnaires. SUMMARY OF BACKGROUND DATA: In addition to low back pain (LBP)
      and neck pain (NP), multiregion spinal pain (SP) is a common problem with a
      considerable prevalence in the general population. The FRI was built to assess
      physical functioning in patients with SP. However, a systematic review assessing
      evidence of its measurement properties in separated populations and a comparison
      with other questionnaires regarding each measurement property is lacking.
      METHODS: Articles concerning the FRI's measurement properties or head-to-head
      comparison with other questionnaires on measurement properties were obtained from
      MEDLINE, Embase, CINAHL, and PsycINFO. Two reviewers independently reviewed the
      articles, extracted data, and conducted the methodological quality assessment.
      The COnsensus-based Standards for the selection of health Measurement INstruments
      (COSMIN) checklist was used to assess the methodological quality of the included
      studies. RESULTS: A total of 18 studies evaluating the FRI's measurement
      properties, including seven that carried out head-to-head comparisons in at least
      one measurement property with other questionnaires, were included in the current
      review. Our findings show strong positive evidence for structural validity and
      internal consistency in patients with SP and LBP. Evidence for most of the FRI's
      measurement properties is limited, conflicting, or even unknown. The current
      evidence shows that the FRI is comparable with both the Oswestry Disability Index
      and the Neck Disability Index in responsiveness. However, relevant information
      about the majority of the other measurement properties is lacking. CONCLUSION:
      Our finding suggests that clinicians and researchers should use the FRI with
      caution until there are more studies with high methodological quality that
      support the view that it is positive in all measurement properties, especially in
      regard to patients with multiregion SP. LEVEL OF EVIDENCE: 1.

PMID- 29659441
TI  - Inter/Intraobserver Reliability of T1 Pelvic Angle (TPA), a Novel Radiographic
      Measure for Global Sagittal Deformity.
AB  - STUDY DESIGN: Reliability analysis. OBJECTIVE: To assess intra- and interobserver
      agreement of the T1 pelvic angle (T1PA), a novel radiographic measure of spinal
      sagittal alignment. Orthopedic surgeons of various levels of experience measured
      the T1PA in a series of healthy adult volunteers. The relationship of the TIPA to
      pelvic position was also assessed. SUMMARY OF BACKGROUND DATA: Recent literature
      suggests that the T1PA is a more reliable measure of global sagittal alignment
      than traditional measurements (i.e., sagittal vertical axis). Previous research
      focuses on postoperative patients with known spinal deformity. No published
      research exists evaluating the use of T1PA on healthy subjects without spinal
      deformity. The purpose of this study is: (1) to assess the reliability of
      measurements of the T1PA, (2) to examine its relationship to pelvic position.
      METHODS: Seven evaluators of varying orthopedic experience measured the T1PA in
      50 healthy adult volunteers. Subjects were radiographed in each of three pelvic
      positions: resting, maximal anterior pelvic rotation, and maximal posterior
      pelvic rotation. After a washout period, the measurement was repeated. Using
      intraclass correlation coefficients, the intra- and inter-rater agreement for the
      T1PA was measured. The collected data was also used to determine the accuracy of
      this measurement and its relationship to pelvic position. RESULTS: A very high
      level of agreement was found in measurements of the T1PA (intraclass correlation
      coefficients r = 0.98). At each pelvic position, all examiners had excellent
      intrarater reliability, > 0.85. The inter-rater reliability, compared with a gold
      standard, consistently measured the T1PA within +/- 2 degrees . The data also
      shows that the T1PA changes with pelvic rotation. CONCLUSION: T1PA is a
      reproducible and reliable measure of global sagittal alignment regardless of the
      level of training. The T1PA varies based on pelvic rotation; this variation must
      be taken into account when assigning an absolute target for correction. LEVEL OF
      EVIDENCE: 4.

PMID- 29659442
TI  - Simplified Chinese Version of the Japanese Orthopaedic Association Back Pain
      Evaluation Questionnaire: Agreement, Responsiveness, and Minimal Important Change
      for Patients With Chronic Low Back Pain.
AB  - STUDY DESIGN: Psychometric test of the cross-cultural adaptation the Japanese
      Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) in low back
      pain (LBP) patients. OBJECTIVE: To investigate the agreement, responsiveness, and
      minimal important change (MIC) of the simplified Chinese version of the JOABPEQ
      in LBP patients. SUMMARY OF BACKGROUND DATA: The factor structure, internal
      consistency, test-retest reliability, validity, floor and ceiling effect of
      simplified Chinese JOABPEQ have been tested, while the agreement, responsiveness,
      and MIC were required. METHODS: The agreement, responsiveness, and MIC of the
      simplified Chinese version were assessed by completing the Chinese JOABPEQ twice.
      Agreement was tested with Bland-Altman plot. Responsiveness was operationalized
      using receiver operating characteristic analyses. The anchor-based method was
      used to calculate MIC. RESULTS: One hundred sixty-two of 184 patients returned to
      finish the booklet twice were available for analysis (response rate: 88.0%).
      While the responsiveness, the area under the curves of each subscale were ranged
      from 0.746 to 0.875, which meant a good responsiveness. While the MIC (MIC%) of
      simplified Chinese JOABPEQ was 19.28 (44.98%) for Q1 Low back pain, 15.20
      (24.13%) for Q2 Lumbar function, 15.79 (22.76%) for Q3 Walking ability, 9.58
      (19.86%) for Q4 Social life function, 7.33 (17.28%) for Q5 Mental health. While
      compared with the MIC, only the Q3 Walking ability had a positive rating for
      agreement in the Bland-Altman plot. CONCLUSION: The simplified Chinese JOABPEQ
      has positive agreement of Q3 Walk ability and acceptable to excellent
      responsiveness of all the subscales. The MICs for subscales of the simplified
      Chinese JOABPEQ ranged from 7.33 to 19.28 points. LEVEL OF EVIDENCE: 3.

PMID- 29659443
TI  - Evaluation of apoptotic pathways in dorsal root ganglion neurons following
      peripheral nerve injury.
AB  - Peripheral nerve injuries induce significant sensory neuronal cell death in the
      dorsal root ganglia (DRG); however, the role of specific apoptotic pathways is
      still unclear. In this study, we performed peripheral nerve transection on adult
      rats, after which the corresponding DRGs were harvested at 7, 14, and 28 days
      after injury for subsequent molecular analyses with quantitative reverse
      transcription-PCR, western blotting, and immunohistochemistry. Nerve injury led
      to increased levels of caspase-3 mRNA and active caspase-3 protein in the DRG.
      Increased expression of caspase-8, caspase-12, caspase-7, and calpain suggested
      that both the extrinsic and the endoplasmic reticulum (ER) stress-mediated
      apoptotic pathways were activated. Phosphorylation of protein kinase R-like ER
      kinase further implied the involvement of ER-stress in the DRG. Phosphorylated
      protein kinase R-like ER kinase was most commonly associated with isolectin B4
      (IB4)-positive neurons in the DRG and this may provide an explanation for the
      increased susceptibility of these neurons to die following nerve injury, likely
      in part because of an activation of the ER-stress response.

PMID- 29659444
TI  - Cerebellar transcranial magnetic stimulation facilitates excitability of spinal
      reflex, but does not affect cerebellar inhibition and facilitation in
      spinocerebellar ataxia.
AB  - Transcranial magnetic stimulation (TMS) over the cerebellum facilitates the
      spinal reflex in healthy humans. The aim of this study was to investigate whether
      such cerebellar spinal facilitation (CSpF) appears in patients with
      spinocerebellar ataxia (SCA) presenting with atrophy in the cerebellar gray
      matter and dentate nucleus. One patient with SCA type 6 and another with SCA type
      31 participated in this study. TMS over the right primary motor cortex was used
      to induce motor-evoked potentials in the right first dorsal interosseous muscle,
      which were detected using electromyography. Conditioning TMS using interstimulus
      intervals of 1-8 ms was performed over the right cerebellum as a test to measure
      cerebellar brain inhibition (CBI). To assess the H-reflex and the M-wave
      recruitment curve of the right soleus muscle, we performed electrical stimulation
      of the right tibial nerve. The stimulation intensity was set to that at the
      center of the H-reflex curve of the ascending limb. To measure CSpF, we delivered
      TMS over the right cerebellum 100, 110, 120, and 130 ms before the right tibial
      nerve stimulation. Voxel-based morphometry was used to verify the presence of
      atrophy in the cerebellar gray matter and dentate nucleus. CBI was absent in both
      cases. However, a significant facilitation of the H-reflex occurred with an
      interstimulus interval of 120 ms in both cases. These findings indicate that the
      pathways associated with the induction of CSpF and CBI are different, and that
      the cerebellar gray matter and dentate nucleus are not needed for the induction
      of CSpF. The possible origin of CSpF may be examined by stimulation of other
      cerebellar deep nuclei or the brainstem.

PMID- 29659445
TI  - Ten-eleven translocation 1 regulates methylation of autophagy-related genes in
      human glioma.
AB  - Ten-eleven translocation 1 catalyzes the conversion of 5-methylcytosine (5mC) to
      5-hydroxymethylcytosine (5hmC), which plays an important role in epigenetics and
      is related to the malignant biological behavior of tumors. However, its
      regulatory role in glioma remains unclear. In this study, the levels of 5mC and
      5hmC were detected using immunohistochemistry, dot-blot, hMeDIP-chip, and western
      blot in glioma tissues and normal brain tissues, whereas 5hmC differentially
      enriched genes were determined and further validated. The level of 5hmC in
      gliomas was decreased, whereas 5mC was increased. 5hmC highly enriched 10
      functional protein-coding genes and 10 signaling pathways were identified using
      hMeGIP-chip in glioma tissues. Two autophagy-related genes, ATG13 and DNA damage
      regulated autophagy modulator protein 1, with low enrichment of 5hmC in glioma
      tissues were verified in the promoter region, and hMeGIP-PCR further confirmed
      this result in U251 cells. Immunohistochemistry further confirmed that autophagy
      level in glioma tissues was lower than that of normal controls, and negatively
      correlated with WHO grade. This study indicates that ten-eleven translocation 1
      may be involved in the development and progression of glioma through
      demethylation regulating a variety of cellular functions and signaling pathways,
      and autophagy is one of the regulatory mechanisms.

PMID- 29659446
TI  - Event-related brain potential correlates of brain reorganization of episodic
      memory throughout the adult lifespan.
AB  - The main aim of this study was to characterize the age-related evolution of the
      event-related brain potentials correlates of successful to tackle the neural
      reorganization patterns associated with this episodic retrieval. We thus examined
      the evolution of the event-related brain potential old/new effect across the
      adult lifespan, in five groups, aged 21-70 years (21-30, 31-40, 41-50, 51-60, and
      61-70 years), equalized on their memory performance through a word-stem cued
      recall task. This procedure makes it possible to examine the evolution of age
      related changes in brain organization during adulthood and to specify the age
      onset of these changes. Results confirm the hypothesis that aging is associated
      with major changes in brain functioning. These changes appear to be consistent
      with both the HAROLD and PASA hypotheses, which postulate an age-related
      reduction in hemispheric asymmetry and a shift from posterior to anterior areas,
      respectively. What is notable is that these patterns of brain reorganization are
      not specific to older stages of life as they begin to develop very early in adult
      life, around the 30s, and the shift toward frontal regions strengthens in the
      60s.

PMID- 29659448
TI  - Reply: Sural Nerve Splitting in Reverse Sural Artery Perforator Flap: Anatomical
      Study in 40 Cadaver Legs.

PMID- 29659447
TI  - The Cost of Contralateral Prophylactic Mastectomy in Women with Unilateral Breast
      Cancer.
AB  - BACKGROUND: Contralateral prophylactic mastectomy may be unnecessary from an
      oncologic perspective; therefore, the debate persists about the value of
      contralateral prophylactic mastectomy in women with early-stage unilateral breast
      cancer. Given finite health care resources, this study aims to evaluate the cost
      of contralateral prophylactic mastectomy and breast reconstruction. METHODS:
      Women with unilateral breast cancer undergoing either unilateral mastectomy or
      unilateral mastectomy with contralateral prophylactic mastectomy and immediate
      breast reconstruction were selected from the Truven MarketScan databases between
      2009 and 2013. Demographic and treatment data were recorded, and over an 18-month
      follow-up period, the treatment cost was tallied. A log-transformed linear model
      was used to compare cost between the groups. RESULTS: A total of 2343 women were
      identified who met our inclusion criteria, with 1295 undergoing unilateral
      mastectomy and 1048 undergoing contralateral prophylactic mastectomy.
      Complication rates within 18 months were similar for women undergoing unilateral
      mastectomy and contralateral prophylactic mastectomy (39 percent versus 42
      percent; p = 0.17). Management with unilateral mastectomy with reconstruction
      required an adjusted cumulative mean cost of $33,557. Contralateral prophylactic
      mastectomy with reconstruction was an additional $11,872 in expenditure (p <
      0.001). The cost of initial procedures (mean difference, $6467) and secondary
      procedures (mean difference, $2455) were the greatest contributors to cost.
      CONCLUSIONS: In women with unilateral breast cancer, contralateral prophylactic
      mastectomy with reconstruction is more costly. The increased monetary cost of
      contralateral prophylactic mastectomy may be offset by improved quality of life.
      However, this financial reality is an important consideration when ongoing
      efforts toward reimbursement reform may not pay for contralateral prophylactic
      mastectomy if outcomes data are not presented to justify this procedure.

PMID- 29659449
TI  - Evolution in Monitoring of Free Flap Autologous Breast Reconstruction after
      Nipple-Sparing Mastectomy: Is There a Best Way?
AB  - BACKGROUND: Free flap monitoring in autologous reconstruction after nipple
      sparing mastectomy remains controversial. The authors therefore examined outcomes
      in nipple-sparing mastectomy with buried free flap reconstruction versus free
      flap reconstruction incorporating a monitoring skin paddle. METHODS: Autologous
      free flap reconstructions with nipple-sparing mastectomy performed from 2006 to
      2015 were identified. Demographics and operative results were analyzed and
      compared between buried flaps and those with a skin paddle for monitoring.
      RESULTS: Two hundred twenty-one free flaps for nipple-sparing mastectomy
      reconstruction were identified: 50 buried flaps and 171 flaps incorporating a
      skin paddle. The most common flaps used were deep inferior epigastric perforator
      (64 percent), profunda artery perforator (12.1 percent), and muscle-sparing
      transverse rectus abdominis myocutaneous flaps (10.4 percent). Patients
      undergoing autologous reconstructions with a skin paddle had a significantly
      greater body mass index (p = 0.006). Mastectomy weight (p = 0.017) and flap
      weight (p < 0.0001) were significantly greater in flaps incorporating a skin
      paddle. Comparing outcomes, there were no significant differences in flap failure
      (2.0 percent versus 2.3 percent; p = 1.000) or percentage of flaps requiring
      return to the operating room (6.0 percent versus 4.7 percent; p = 0.715) between
      groups. Buried flaps had an absolute greater mean number of revision procedures
      per nipple-sparing mastectomy (0.82) compared with the skin paddle group (0.44);
      however, rates of revision procedures per nipple-sparing mastectomy were
      statistically equivalent between the groups (p = 0.296). CONCLUSION: Although
      buried free flap reconstruction in nipple-sparing mastectomy has been shown to be
      safe and effective, the authors' technique has evolved to favor incorporating a
      skin paddle, which allows for clinical monitoring and can be removed at the time
      of secondary revision. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

PMID- 29659450
TI  - Aseptic Freeze-Dried versus Sterile Wet-Packaged Human Cadaveric Acellular Dermal
      Matrix in Immediate Tissue Expander Breast Reconstruction: A Propensity Score
      Analysis.
AB  - BACKGROUND: Although multiple acellular dermal matrix sources exist, it is
      unclear how its processing impacts complication rates. The authors compared
      complications between two preparations of human cadaveric acellular dermal matrix
      (freeze dried and ready-to-use) in immediate tissue expander breast
      reconstruction to analyze the effect of processing on complications. METHODS: The
      authors retrospectively reviewed all alloplastic breast reconstructions with
      freeze-dried or ready-to-use human acellular dermal matrices between 2006 and
      2016. The primary outcome measure was surgical-site occurrence defined as seroma,
      skin dehiscence, surgical-site infection, or reconstruction failure. The two
      groups were compared before and after propensity score matching. RESULTS: The
      authors included 988 reconstructions (freeze-dried, 53.8 percent; ready-to-use,
      46.2 percent). Analysis of 384 propensity score-matched pairs demonstrated a
      slightly higher rate of surgical-site occurrence (21.4 percent versus 16.7
      percent; p = 0.10) and surgical-site infection (9.6 percent versus 7.8 percent; p
      = 0.13) in the freeze-dried group than in the ready-to-use group, but the
      difference was not significant. However, failure was significantly higher for the
      freeze-dried versus ready-to-use group (7.8 percent versus 4.4 percent; p =
      0.050). CONCLUSIONS: This is the largest study comparing the outcomes of
      alloplastic breast reconstruction using human acellular dermal matrix materials
      prepared by different methods. The authors demonstrated higher early
      complications with aseptic, freeze-dried matrix than with sterile ready-to-use
      matrix; reconstructive failure was the only outcome to achieve statistical
      significance. The authors conclude that acellular dermal matrix preparation has
      an independent impact on patient outcomes in their comparison of one company's
      product. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

PMID- 29659451
TI  - The Use of Surgical Delay for Partial Mastectomy Reconstruction in the Previously
      Irradiated Breast: A Matched-Control Case Series.

PMID- 29659452
TI  - Supratrochlear Artery Based Periosteal Flaps: A New Alternative Technique for
      Nasal Lining Reconstruction.

PMID- 29659453
TI  - Commentary on: Supratrochlear Artery Based Periosteal Flaps: A New Alternative
      Technique for Nasal Lining Reconstruction.

PMID- 29659454
TI  - Adipose Tissue-Preserved Skin Graft: Applicability and Long-Term Results.

PMID- 29659455
TI  - Miller-Meyerson Maneuver for Left-Handed Surgeons.

PMID- 29659456
TI  - Philtrum Repair in Upper Lip Recosntruction.

PMID- 29659457
TI  - Reply: Upper Lip Reconstruction.

PMID- 29659458
TI  - Reply: Evidence-Based Medicine: Current Evidence in the Diagnosis and Management
      of Carpal Tunnel Syndrome.

PMID- 29659459
TI  - Pediatric Zygomaticomaxillary Complex Fracture Repair: Location and Number of
      Fixation Sites in Growing Children.
AB  - BACKGROUND: Relatively few reports have been published investigating the
      operative management of pediatric zygomaticomaxillary complex fractures. The
      purpose of this study was to assess pediatric zygomaticomaxillary complex
      fracture management and associated complications, and potentially describe a
      standard treatment paradigm for these cases. METHODS: A retrospective cohort
      review was performed of all patients younger than 15 years presenting to a single
      institution with zygomaticomaxillary complex fractures from 1990 to 2010. Patient
      demographics, concomitant injuries, management details, and complications were
      recorded. Complications were compared among patients by dentition stage, number
      of fixation points, and identity of fixation sites. RESULTS: A total of 36
      patients with 44 unique zygomaticomaxillary complex fractures met the authors'
      inclusion criteria. Thirty-two fractures exhibited at least 2.0 mm of diastasis
      along at least one buttress (73 percent), and all but one of these were managed
      operatively. Among operatively managed patients with deciduous dentition, two
      point fixation was associated with a lower overall complication rate compared
      with one- and three-point fixation (0 percent versus 75 percent and 75 percent; p
      = 0.01). Furthermore, rigid plate-and-screw fixation at the zygomaticomaxillary
      buttress was not associated with an increased complication rate in operatively
      managed patients with deciduous dentition (40 percent versus 50 percent; p =
      0.76). CONCLUSIONS: The authors' results suggest that two-point fixation is an
      effective management strategy for repair of displaced zygomaticomaxillary complex
      fractures in children. In addition, rigid plate-and-screw fixation at the
      zygomaticomaxillary buttress in children with deciduous dentition appears to be
      safe and effective when performed. CLINICAL QUESTION/LEVEL OF EVIDENCE:
      Therapeutic, III.

PMID- 29659460
TI  - Clozapine Titration for People in Early Psychosis: A Chart Review and Treatment
      Guideline.
AB  - PURPOSE/BACKGROUND: The use of clozapine, particularly in young people, is often
      limited by early treatment-emergent adverse effects including drowsiness and
      lethargy. Concerns about adverse effects, medication adherence, and the need for
      blood monitoring often impede the use of clozapine in this population, leading to
      repeated trials of less effective medications. Current clozapine dosing
      recommendations are based on people further in the course of their illness and
      thus reflect different responsiveness and sensitivities to antipsychotic
      medication. As such, there is a need for evidence-based guidelines for titration
      and dosing of clozapine among people in early psychosis. METHODS/PROCEDURES: We
      performed a chart review of 14 people treated with clozapine within our early
      psychosis team. Data regarding dose titration, response, time to discontinuation,
      symptom severity, weight gain, and other adverse effects were gathered at
      clozapine initiation, 3 months, and last available visit on clozapine.
      FINDINGS/RESULTS: People treated with slow titration within their first year of
      psychosis onset achieved sustained response at very low maintenance doses (mean
      dose = 81 mg/d, mean duration of treatment = 200 weeks) compared with slow
      titration with longer duration of illness (mean dose = 350 mg/d, mean duration of
      treatment = 68 weeks) or standard dose titration in early psychosis (mean dose =
      112 mg/d, mean duration of treatment = 38 weeks). The most common adverse effects
      in all groups were weight gain and sedation, with the groups requiring higher
      mean doses reporting a broader range of adverse effects. There was no apparent
      difference in the clinical global impression for severity or improvement between
      the slow titration and standard titration groups in people with early psychosis.
      These observations are synthesized into a proposed treatment guideline for use of
      clozapine among people in early psychosis. IMPLICATIONS/CONCLUSIONS: We describe
      development of a slow titration approach to initiating clozapine among people in
      early psychosis. This approach resulted in clinical response at remarkably low
      maintenance doses of clozapine among people within their first year of illness,
      but not in those with longer duration of symptoms. Slow titration also led to
      good tolerability and acceptance of clozapine treatment for some patients.

PMID- 29659461
TI  - The Year of Advocacy.

PMID- 29659462
TI  - Making an Infusion Error: The Second Victims of Infusion Therapy-Related
      Medication Errors.
AB  - Infusion therapy-related adverse events can result in distress and professional
      suffering for the nurse involved with the event, with long-lasting consequences.
      This article discusses the second victim syndrome and its impacts on nurses.
      Original research on 168 recent nursing graduates and their experiences with
      second victim syndrome after making an infusion-related error is also presented.
      The article concludes with strategies to help nurses cope with the aftermath of
      making an infusion therapy-related medication error.

PMID- 29659463
TI  - Maintaining Short Peripheral Catheter Patency: A Comparison of Saline Lock Versus
      Continuous Infusion in the Acute Care Setting.
AB  - Sparse evidence exists about how short peripheral catheter (SPC) duration is
      affected by the presence of a saline lock versus continually infusing fluids.
      Often the choice to lock an SPC with saline is based on provider preference,
      rather than available evidence or patient-centered factors. This study compared
      the duration of 85 SPCs: locked with saline versus continuously running fluids. A
      secondary analysis considered the influence of a number of intermittent
      medications and flushes. Although the saline-locked group had a slightly longer
      duration time, it was not statistically significant. Factors such as desire to
      ambulate or nighttime saline flushes merit consideration in SPC care decisions
      and standardized nurse-driven protocols.

PMID- 29659464
TI  - Transitioning Patients With Iron Overload From Exjade to Jadenu.
AB  - Iron overload is a concern for patients who require chronic transfusions as a
      result of inherited or acquired anemias, including sickle cell disease,
      thalassemia, and myelodysplastic syndromes. Iron chelation therapy (ICT) is the
      primary treatment for iron overload in these patients. The ICT deferasirox, which
      has been available as an oral dispersible tablet for liquid suspension, is now
      also available as a once-daily, film-coated tablet (FCT). Deferasirox FCT allows
      greater convenience and may be associated with fewer gastrointestinal side
      effects versus the original formulation. Dose adjustment increments, determined
      by titration monitoring, are lower for the FCT because of greater
      bioavailability.

PMID- 29659465
TI  - Does Hyperglycemia Affect Risk of Peripherally Inserted Central Catheter-Related
      Upper Extremity Venous Thrombosis?
AB  - It is not clear whether blood glucose (BG) affects the risk of peripherally
      inserted central catheter (PICC)-related upper extremity venous thrombosis
      (PRUEVT). A case-control study was conducted comparing patients with PRUEVT
      versus patients with PICCs who did not develop PRUEVT. BG on admission was
      significantly higher among cases with PRUEVT than controls. No significant
      differences were found between the groups in hemoglobin A1c or BG on the third
      day of hospitalization. PRUEVT cases were more likely to be diabetic, but this
      did not reach statistical significance. The time that a PICC was in place before
      PRUEVT was diagnosed was longer for diabetic patients, but the authors believe
      this result must be viewed with caution.

PMID- 29659466
TI  - Levels of Hemolysis Markers in Erythrocyte Concentrates Administered Using a
      Syringe Infusion Pump.
AB  - Syringe infusion pumps (SIPs) led to major advances in infusion therapy and were
      gradually applied to the transfusion of packed red blood cells (RBCs), raising
      questions about possible cell damage. The objectives of this study were to
      determine levels of hematocrit (%), total hemoglobin (g/dL), free hemoglobin
      (g/dL), lactate dehydrogenase (units/L), potassium (mmol/L), the degree of
      hemolysis (%) of RBCs infused by an SIP, and to investigate the influence of the
      infusion rate. The experimental study comprised 14 RBCs, 3 SIPs, and infusion
      rates of 5, 10, and 20 mL/h. The results showed total hemoglobin reduction (P =
      .003), and increased free hemoglobin and hemolysis (P <.001) were identified. The
      conclusion reached was that RBCs presented changes in free hemoglobin and degree
      of hemolysis.

PMID- 29659468
TI  - Routine Versus Clinically Indicated Short Peripheral Catheter Replacement: An
      Evidence-based Practice Project.
AB  - Despite current, high-quality, level 1 evidence that supports clinically
      indicated short peripheral catheter (SPC) replacement, the current practice in
      the health care system studied was to change SPCs routinely every 96 hours. A
      before-and-after design was used to evaluate the impact of SPC replacement when
      clinically indicated. Following the practice change, there were no SPC-related
      infections, monthly phlebitis rates ranged from 1.9% to 3.5%, and SPC use
      decreased by 14.2%, resulting in estimated cost savings of $2100 and 70 hours of
      nursing time saved. The translation of evidence on timing of SPC replacement into
      practice was a success.

PMID- 29659469
TI  - Alloknesis and hyperknesis-mechanisms, assessment methodology, and clinical
      implications of itch sensitization.
AB  - Itch and pain share numerous mechanistic similarities. Patients with chronic itch
      conditions (for instance atopic dermatitis or neuropathic itch) often experience
      symptoms such as mechanical alloknesis and hyperknesis. These dysesthesias are
      analogous to the pain-associated phenomena allodynia and hyperalgesia, which are
      often observed, for example, in neuropathic pain conditions. Mechanical itch
      dysesthesias represent abnormal sensory states (caused by neuroplastic changes),
      wherein considerable itch is evoked, for instance by light cutaneous stimuli such
      as from clothing (alloknesis), or where increased itch is perceived in response
      to normally itch-evoking stimuli (hyperknesis). These itch sensitization
      phenomena have been explored in experimental human studies, observed in chronic
      itch patients, and in animal models of itch. Limited attention has been paid to
      these sensory phenomena in clinical studies, and it is unknown how they respond
      to antipruritics. Psychophysical quantitative sensory testing can quantify the
      presence, severity, and spatial extent of itch dysesthesias in chronic itch
      patients, providing a proxy measurement of itch sensitization. This review
      outlines current assessment techniques, knowledge on the mechanisms of mechanical
      alloknesis and hyperknesis, and presents the diverse results derived from
      clinical studies exploring the presence of itch dysesthesias in chronic itch
      patients. A key role of quantitative sensory testing and neuronal sensitization
      in patients with chronic pain is accepted and used in clinical assessments.
      However, the precise mechanisms and potential clinical implications of itch
      sensitization in chronic itch patients remain to be evaluated.

PMID- 29659467
TI  - A Standard Push-Pull Protocol for Waste-Free Sampling in the Pediatric Intensive
      Care Unit.
AB  - Blood sampling is a major source of blood loss in the pediatric intensive care
      unit (PICU). Blood-sparing sampling techniques such as the push-pull method can
      significantly reduce sampling-related blood loss and protect patients from anemia
      and blood transfusions. The push-pull method is supported by research evidence
      for central venous catheter (CVC) sampling, but research protocols differ and not
      all CVCs and laboratory tests have been studied. A standard push-pull protocol
      for the PICU was developed, implemented, and evaluated in this evidence-based
      practice project. Results show that the protocol can be used safely and reliably
      as a standard waste-free sampling method in the PICU.

PMID- 29659470
TI  - Meta-analysis of perioperative outcomes of acute laparoscopic versus open repair
      of perforated gastroduodenal ulcers.
AB  - BACKGROUND: Surgery is the treatment of choice for perforated peptic ulcer
      disease. The aim of the present review was to compare the perioperative outcomes
      of acute laparoscopic versus open repair for peptic ulcer disease. METHODS: A
      systematic literature search was performed for randomized controlled trials
      (RCTs) published in PubMed, SCOPUS, and Web of Science. RESULTS: The search
      included eight RCTs: 615 patients comparing laparoscopic (307 patients) versus
      open peptic perforated ulcer repair (308 patients). Only few studies reported the
      Boey score, the Acute Physiologic Assessment and Chronic Health Evaluation score,
      and the Mannheim Peritonitis Index. In the RCTs, there is a significant
      heterogeneity about the gastric or duodenal location of peptic ulcer and
      perforation size. All trials were with high risk of bias. This meta-analysis
      reported a significant advantage of laparoscopic repair only for postoperative
      pain in first 24 hours (-2.08; 95% confidence interval, -2.79 to -1.37) and for
      postoperative wound infection (risk ratio, 0.39; 95% confidence interval, 0.23
      0.66). An equivalence of the other clinical outcomes (postoperative mortality
      rate, overall reoperation rate, overall leaks of the suture repair, intra
      abdominal abscess rate, operative time of postoperative hospital stay,
      nasogastric aspiration time, and time to return to oral diet) was reported.
      CONCLUSION: In this meta-analysis, there were no significant differences in most
      of the clinical outcomes between the two groups; there was less early
      postoperative pain and fewer wound infections after laparoscopic repair. The
      reported equivalence of clinical outcomes is an important finding. These results
      parallel the results of several other comparisons of open versus laparoscopic
      general surgery operations-equally efficacious with lower rates of wound
      infection and improvement in some measures of enhanced speed or comfort in
      recovery. Notably, the trials included have been published throughout a
      considerable time span during which several changes have occurred in most health
      care systems, not least a widespread use of laparoscopy and increase in the
      laparoscopic skills. LEVEL OF EVIDENCE: Systematic review and meta-analysis,
      level III.

PMID- 29659471
TI  - Management of colorectal injuries: A Western Trauma Association critical
      decisions algorithm.

PMID- 29659472
TI  - Evaluation and management of abdominal stab wounds: A Western Trauma Association
      critical decisions algorithm.
AB  - This is a recommended management algorithm from the Western Trauma Association
      addressing the management of adult patients with abdominal stab wounds. Because
      there is a paucity of published prospective randomized clinical trials that have
      generated Class I data, these recommendations are based primarily on published
      observational studies and expert opinion of Western Trauma Association members.
      The algorithm and accompanying comments represent a safe and sensible approach
      that can be followed at most trauma centers. We recognize that there will be
      patient, personnel, institutional, and situational factors that may warrant or
      require deviation from the recommended algorithm. We encourage institutions to
      use this as a guideline to develop their own local protocols.

PMID- 29659473
TI  - External validation of a five-variable clinical prediction rule for identifying
      children at very low risk for intra-abdominal injury after blunt abdominal
      trauma.
AB  - BACKGROUND: A clinical prediction rule was previously developed by the Pediatric
      Surgery Research Collaborative (PedSRC) to identify patients at very low risk for
      intra-abdominal injury (IAI) and intra-abdominal injury receiving an acute
      intervention (IAI-I) who could safely avoid abdominal computed tomography (CT)
      scans after blunt abdominal trauma (BAT). Our objective was to externally
      validate the rule. METHODS: The public-use dataset was obtained from the
      Pediatric Emergency Care Applied Research Network (PECARN) Intra-abdominal Injury
      Study. Patients 16 years of age and younger with chest x-ray, completed abdominal
      history and physical examination, aspartate aminotransferase (AST), and amylase
      or lipase collected within 6 hours of arrival were included. We excluded patients
      who presented greater than 6 hours after injury or missing any of the five
      clinical prediction variables from the PedSRC prediction rule. RESULTS: We
      included 2,435 patients from the PECARN dataset, with a mean age of 9.4 years.
      There were 235 patients with IAI (9.7%) and 60 patients with IAI-I (2.5%). The
      clinical prediction rule had a sensitivity of 97.5% for IAI and 100% for IAI-I.
      In patients with no abnormality in any of the five prediction rule variables, the
      rule had a negative predictive value of 99.3% for IAI and 100.0% for IAI-I. Of
      the "very low-risk" patients identified by the rule, 46.8% underwent abdominal CT
      imaging. CONCLUSIONS: A highly sensitive clinical prediction rule using history
      and abdominal physical examination, laboratory values, and chest x-ray was
      successfully validated using a large public-access dataset of pediatric BAT
      patients. LEVEL OF EVIDENCE: Epidemiologic/prognostic study, level III;
      therapeutic care/management study, level IV.

PMID- 29659474
TI  - Comparing appendectomies performed by trauma surgeons and pediatric surgeons in
      children 5 to 10 years of age.

PMID- 29659475
TI  - Frailty screening and a frailty pathway decrease length of stay, loss of
      independence, and 30-day readmission rates in frail geriatric trauma and
      emergency general surgery patients.
AB  - BACKGROUND: Frail geriatric trauma and emergency general surgery (TEGS) patients
      have longer lengths of stay (LOS), more readmissions, and higher rates of
      postdischarge institutionalization than their nonfrail counterparts. Despite
      calls to action by national trauma coalitions, there are few published reports of
      prospective interventions. The objective of this quality improvement project was
      to first develop a frailty screening program, and, then, if frail, implement a
      novel frailty pathway to reduce LOS, 30-day readmissions, and loss of
      independence. METHODS: This was a before-after study of a prospective cohort of
      all geriatric (>=65-years-old) patients admitted to the TEGS service from October
      2016 to October 2017. All patients were screened for frailty for 3 months
      (preintervention) to obtain baseline outcomes. Subsequently, frail patients were
      entered into our frailty pathway (postintervention). Nonparametric statistical
      tests were used to assess significant differences in continuous variables; chi
      and Fisher exact tests were used for categorical variables, where appropriate.
      Both process and outcome measures were evaluated. RESULTS: Of 239 geriatric TEGS
      patients screened, 70 (29.3%) were frail. All TEGS geriatric patients were
      screened within 24 hours of admission. Following frailty pathway implementation,
      median LOS for frail patients decreased from 9 to 6 days (p = 0.4), readmissions
      decreased from 36.4% to 10.2% (p = 0.04), and loss of independence decreased by
      40%, (100% vs 60%; p = 0.01). Outcomes for nonfrail geriatric patients did not
      differ between cohorts. CONCLUSIONS: Screening for frailty followed by
      implementing a frailty pathway decreased LOS, loss of independence, and 30-day
      readmission rates for frail geriatric TEGS patients at a single urban academic
      institution. The pathway required no additional resources; rather, we shifted
      focus toward frail patients without negatively affecting outcomes in nonfrail
      geriatric TEGS patients. Implementation of this pathway with larger patient
      cohorts and in varied settings is needed to confirm a causal relationship between
      our intervention and improved outcomes. LEVEL OF EVIDENCE: Therapeutic study,
      level IV.

PMID- 29659476
TI  - Prospective evaluation of low health literacy and its impact on outcomes in
      trauma patients.
AB  - BACKGROUND: Health literacy is an emerging focus of interest in public health and
      is evolving as an important component of national health policy. Low health
      literacy (LHL) is associated with poor outcomes. We aimed to identify factors
      associated with LHL and its relationship with health outcomes in trauma patients.
      METHODS: We prospectively enrolled all adult trauma patients (age, > 18 years) in
      our analysis. Patients were surveyed at discharge and followed up at 4 weeks
      postdischarge. At discharge, patient's health literacy was assessed using the
      Short-Assessment of Health Literacy score. Low health literacy was defined as
      Short-Assessment of Health Literacy score less than 14. Patients were surveyed
      regarding their understanding of their injuries, treatment received, discharge
      instructions, and interaction with the physician. Four weeks postdischarge, all
      patients were inquired about clinic follow-up details and recovery. RESULTS: We
      enrolled 140 patients, of which 70% were white. Mean age was 45 +/- 20 years, and
      median Injury Severity Score was 10 (6-12). Overall, 24% (34) patients had LHL.
      There was no difference in the Injury Severity Score between LHL and health
      literate (HL) patients (p = 0.41). The LHL patients were more likely to be
      Hispanic-white (78% vs. 41%, p = 0.02), had lower socioeconomic status (91% vs.
      51%, p = 0.01), uninsured (45% vs. 18%, p = 0.01), and were less likely to have
      graduated (0% vs. 49%, p = 0.01) compared with the HL patients. At discharge,
      both groups were satisfied with the time spent by a physician to explain the
      condition, however, the LHL patients were less likely to recall their injuries (p
      = 0.03) or how they were treated (p = 0.01). Patients with LHL had lower follow
      up rates (p = 0.01) with no difference in the readmission rate (p = 0.71)
      compared with HL. CONCLUSION: Every 1 in 4 trauma patients have LHL. Low health
      literacy is associated with poor understanding of injuries and treatment provided
      to them, leading to a decrease in compliance with discharge instructions and
      longer time to recovery. Identifying LHL in high-risk patients and developing
      appropriate intervention before discharge may help improve outcomes. LEVEL OF
      EVIDENCE: Prognostic study, level I.

PMID- 29659477
TI  - Alpha-Toxin Contributes to Biofilm Formation among Staphylococcus aureus Wound
      Isolates.
AB  - Biofilms complicate treatment of Staphylococcus aureus (SA) wound infections.
      Previously, we determined alpha-toxin (AT)-promoted SA biofilm formation on
      mucosal tissue. Therefore, we evaluated SA wound isolates for AT production and
      biofilm formation on epithelium and assessed the role of AT in biofilm formation.
      Thirty-eight wound isolates were molecularly typed by pulsed-field gel
      electrophoresis (PFGE), multilocus sequence typing (ST), and spa typing. We
      measured biofilm formation of these SA isolates in vitro and ex vivo and
      quantified ex vivo AT production. We also investigated the effect of an anti-AT
      monoclonal antibody (MEDI4893*) on ex vivo biofilm formation by methicillin
      resistant SA (USA 300 LAC) and tested whether purified AT rescued the biofilm
      defect of hla mutant SA strains. The predominant PFGE/ST combinations were
      USA100/ST5 (50%) and USA300/ST8 (33%) for methicillin-resistant SA (MRSA, n =
      18), and USA200/ST30 (20%) for methicillin-susceptible SA (MSSA, n = 20). Ex vivo
      AT production correlated significantly with ex vivo SA wound isolate biofilm
      formation. Anti-alpha-toxin monoclonal antibody (MEDI4893*) prevented ex vivo
      biofilm formation by MRSA USA300 strain LAC. Wild-type AT rescued the ex vivo
      biofilm defect of non-AT producing SA strains. These findings provide evidence
      that AT plays a role in SA biofilm formation on epithelial surfaces and suggest
      that neutralization of AT may be useful in preventing and treating SA infections.

PMID- 29659478
TI  - Taekwondo Training Improves Mood and Sociability in Children from Multicultural
      Families in South Korea: A Randomized Controlled Pilot Study.
AB  - PURPOSE: Children from multicultural families face physical, social, mental, and
      intellectual hurdles; however, relative interventions are lacking in South Korea
      (hereafter Korea) in this regard. The purpose of this study was to investigate
      the effects of regular Taekwondo (TKD) training on physical fitness, mood,
      sociability, and cognitive functions in these children. METHODS: This study
      included 30 children from multicultural families in Korea who were randomly
      assigned to a TKD group (n = 15) and control group (n = 15). The children in TKD
      group underwent 16 weeks of TKD training once a week for 60 min. Each participant
      underwent a basic fitness test and sociability questionnaire before and after the
      intervention. Furthermore, we examined the changes in the mood and cognitive
      function by determining the profile of mood states (POMS), and Stroop color and
      word test, respectively. RESULTS: Results of the Stork test of balance were
      significantly higher in the TKD group after intervention (p < 0.05). In terms of
      sub-variables, POMS, tension, and depression scores were significantly lower (p <
      0.05) after the intervention, while the vigor score was significantly higher in
      the intervention group than those in the control group (p < 0.05). Furthermore,
      sociability and 'being left out' score, a sub-variable of sociability, was
      significantly lower (p < 0.05) after the intervention, while sociability score
      was significantly higher (p < 0.05). CONCLUSIONS: Our findings suggest that
      participation in regular TKD training can be effective for balanced improvements
      in variables of basic fitness and that it exerts a positive effect on the mood
      and development of sociability.

PMID- 29659479
TI  - Oral Dysbiotic Communities and Their Implications in Systemic Diseases.
AB  - The human body supports the growth of a wide array of microbial communities in
      various niches such as the oral cavity, gastro-intestinal and urogenital tracts,
      and on the surface of the skin. These host associated microbial communities
      include yet-un-cultivable bacteria and are influenced by various factors.
      Together, these communities of bacteria are referred to as the human microbiome.
      Human oral microbiome consists of both symbionts and pathobionts. Deviation from
      symbiosis among the bacterial community leads to &ldquo;dysbiosis&rdquo;, a state
      of community disturbance. Dysbiosis occurs due to many confounding factors that
      predispose a shift in the composition and relative abundance of microbial
      communities. Dysbiotic communities have been a major cause for many microbiome
      related systemic infections. Such dysbiosis is directed by certain important
      pathogens called the &ldquo;keystone pathogens&rdquo;, which can modulate
      community microbiome variations. One such persistent infection is oral infection,
      mainly periodontitis, where a wide array of causal organisms have been implied to
      systemic infections such as cardio vascular disease, diabetes mellitus,
      rheumatoid arthritis, and Alzheimer&rsquo;s disease. The keystone pathogens co
      occur with many yet-cultivable bacteria and their interactions lead to dysbiosis.
      This has been the focus of recent research. While immune evasion is one of the
      major modes that leads to dysbiosis, new processes and new virulence factors of
      bacteria have been shown to be involved in this important process that determines
      a disease or health state. This review focuses on such dysbiotic communities,
      their interactions, and their virulence factors that predispose the host to other
      systemic implications.

PMID- 29659480
TI  - Source Apportionment of Polycyclic Aromatic Hydrocarbons in Sediment by the
      Application of Non-Negative Factor Analysis: A Case Study of Dalian Bay.
AB  - An improved method, factor analysis with non-negative constraints (FA-NNC) was
      adopted to apportion the sources of sediment polycyclic aromatic hydrocarbons
      (PAHs) in Dalian Bay, China. Cosine similarity and Monte Carlo uncertainty
      analysis were used to assist the FA-NNC source resolution. The results identified
      three sources for PAHs, which were overall traffic, diesel engine emissions and
      residential coal combustion. The contributions of these sources were quantified
      as 78 &plusmn; 4.6% from overall traffic, 12 &plusmn; 3.2% from diesel engine
      emissions, and 10 &plusmn; 1.9% from residential coal combustion. The results
      from the Monte Carlo uncertainty analysis indicated that the model was robust and
      convergent.

PMID- 29659481
TI  - Retooling CalEnviroScreen: Cumulative Pollution Burden and Race-Based
      Environmental Health Vulnerabilities in California.
AB  - The California Community Environmental Health Screening Tool (CalEnviroScreen)
      advances research and policy pertaining to environmental health vulnerability.
      However, CalEnviroScreen departs from its historical foundations and comparable
      screening tools by no longer considering racial status as an indicator of
      environmental health vulnerability and predictor of cumulative pollution burden.
      This study used conceptual frameworks and analytical techniques from
      environmental health and inequality literature to address the limitations of
      CalEnviroScreen, especially its inattention to race-based environmental health
      vulnerabilities. It developed an adjusted measure of cumulative pollution burden
      from the CalEnviroScreen 2.0 data that facilitates multivariate analyses of the
      effect of neighborhood racial composition on cumulative pollution burden, net of
      other indicators of population vulnerability, traffic density, industrial zoning,
      and local and regional clustering of pollution burden. Principal component
      analyses produced three new measures of population vulnerability, including
      Latina/o cumulative disadvantage that represents the spatial concentration of
      Latinas/os, economic disadvantage, limited English-speaking ability, and health
      vulnerability. Spatial error regression analyses demonstrated that concentrations
      of Latinas/os, followed by Latina/o cumulative disadvantage, are the strongest
      demographic determinants of adjusted cumulative pollution burden. Findings have
      implications for research and policy pertaining to cumulative impacts and race
      based environmental health vulnerabilities within and beyond California.

PMID- 29659482
TI  - Educational Attainment and Smoking Status in a National Sample of American
      Adults; Evidence for the Blacks' Diminished Return.
AB  - BACKGROUND: Although higher socioeconomic status (SES) indicators such as
      educational attainment are linked with health behaviors, the Blacks&rsquo;
      Diminished Return theory posits that the protective effects of SES are
      systemically smaller for Blacks than Whites. AIMS: To explore the Black/White
      differences in the association between education and smoking. METHODS: This cross
      sectional study used the Health Information National Trends Survey (HINTS) 2017
      (n = 3217). HINTS is a national survey of American adults. The current analysis
      included 2277 adults who were either Whites (n = 1868; 82%) or Blacks (n = 409;
      18%). The independent variable was educational attainment, and the dependent
      variables were ever and current (past 30-day) smoking. Demographic factors (age
      and gender) were covariates. Race was the focal moderator. RESULTS: In the pooled
      sample, higher educational attainment was associated with lower odds of ever and
      current smoking. Race interacted with the effects of higher educational
      attainment on current smoking, suggesting a stronger protective effect of higher
      education against current smoking for Whites than Blacks. Race did not interact
      with the effect of educational attainment on odds of ever smoking. CONCLUSIONS:
      In line with previous research in the United States, education is more strongly
      associated with health and health behaviors in Whites than Blacks. Smaller
      protective effects of education on health behaviors may be due to the existing
      racism across institutions such as the education system and labor market.

PMID- 29659483
TI  - Lewis Pair Polymerization for New Reactivity and Structure in Polymer Synthesis.

PMID- 29659484
TI  - Fretting Wear Damage Mechanism of Uranium under Various Atmosphere and Vacuum
      Conditions.
AB  - A fretting wear experiment with uranium has been performed on a linear
      reciprocating tribometer with ball-on-disk contact. This study focused on the
      fretting behavior of the uranium under different atmospheres (Ar, Air (21% O2 +
      78% N2), and O2) and vacuum conditions (1.05 and 1 &times; 10&minus;4 Pa).
      Evolution of friction was assessed by coefficient of friction (COF) and friction
      dissipated energy. The oxide of the wear surface was evaluated by Raman
      spectroscopy. The result shows that fretting wear behavior presents strong
      atmosphere and vacuum condition dependence. With increasing oxygen content, the
      COF decreases due to abrasive wear and formation of oxide film. The COF in the
      oxygen condition is at least 0.335, and it has a maximum wear volume of about
      1.48 &times; 107 &mu;m3. However, the COF in a high vacuum condition is maximum
      about 1.104, and the wear volume is 1.64 &times; 106 &mu;m3. The COF in the low
      vacuum condition is very different: it firstly increased and then decreased
      rapidly to a steady value. It is caused by slight abrasive wear and the formation
      of tribofilm after thousands of cycles.

PMID- 29659485
TI  - Continuous-Wave Fiber Cavity Ringdown Pressure Sensing Based on Frequency-Shifted
      Interferometry.
AB  - We present a continuous-wave fiber cavity ringdown (FCRD) pressure-sensing method
      based on frequency-shifted interferometry (FSI). Compared with traditional CRD or
      FCRD techniques, this FSI-FCRD scheme deduces pressure by measuring the decay
      rate of continuous light exiting the fiber ringdown cavity (RDC) in the spatial
      domain (i.e., the CRD distance), without the requirement for optical pulsation
      and fast electronics. By using a section of fiber with the buffer layer stripped
      in the fiber RDC as the sensor head, pressures were measured within the range
      from 0 to 10.4 MPa. The sensitivity of 0.02356/(km?MPa) was obtained with a
      measurement error of 0.1%, and the corresponding pressure resolution was 0.05
      MPa. It was found that the measurement sensitivity can be improved by enlarging
      the interaction length of the sensor head. The results show the proposed sensor
      has the advantages of simple structure, low cost, high sensitivity, and high
      stability in pressure detection.

PMID- 29659487
TI  - Cultivar and Harvest Month Influence the Nutrient Content of Opuntia spp. Cactus
      Pear Cladode Mucilage Extracts.
AB  - Mucilage extracted from cactus pear cladodes is a hydrocolloid gum. It is a
      novel, natural, low-kilojoule, cost-effective texture-modifying ingredient in
      functional food products. Yet, the cultivar with the most optimal nutrient
      content and the preferred harvest times are as yet unknown. For this reason,
      mucilage from three Opuntia ficus-indica (Algerian, Morado and Gymno-Carpo) and
      one Opuntia robusta (Robusta) cultivar were investigated to determine their
      nutrient content over six months. Nutrients that contribute energy (10.2 kJ/g)
      were low. The mineral content was high (ash 17.7/100 g), particularly calcium
      (3.0 g/100 g) and phosphorous (109.5 mg/kg). Low insoluble acid-detergent fibre
      (1.4 g/kg) and neutral-detergent fibre (2.1 g/kg) values indicated that mucilage
      was mostly soluble fibre. Calcium oxalate crystals were not detected in dried
      mucilage. Opuntia robusta powders had higher protein, extractable fat and
      potassium content, while Opuntia ficus-indica mucilage powders had higher
      polyunsaturated (Linoleic and &alpha;-Linolenic acid) fat content. O. robusta
      Robusta mucilage, harvested after the fruit harvest (February) had the lowest
      energy content and the highest mineral and protein content. Mucilage powders were
      highly soluble, low-kilojoule and mineral-rich. This is a functional ingredient
      that is produced from an easily cultivated crop, as cactus pears grow in areas
      with poor soil, extremely high daytime temperatures and limited water supplies.

PMID- 29659486
TI  - Vascular Endothelial Growth Factor-A Exerts Diverse Cellular Effects via Small G
      Proteins, Rho and Rap.
AB  - Vascular endothelial growth factors (VEGFs) include five molecules (VEGF-A, -B, 
      C, -D, and placental growth factor), and have various roles that crucially
      regulate cellular functions in many kinds of cells and tissues. Intracellular
      signal transduction induced by VEGFs has been extensively studied and is usually
      initiated by their binding to two classes of transmembrane receptors: receptor
      tyrosine kinase VEGF receptors (VEGF receptor-1, -2 and -3) and neuropilins (NRP1
      and NRP2). In addition to many established results reported by other research
      groups, we have previously identified small G proteins, especially Ras homologue
      gene (Rho) and Ras-related protein (Rap), as important mediators of VEGF-A
      stimulated signaling in cancer cells as well as endothelial cells. This review
      article describes the VEGF-A-induced signaling pathways underlying diverse
      cellular functions, including cell proliferation, migration, and angiogenesis,
      and the involvement of Rho, Rap, and their related molecules in these pathways.

PMID- 29659488
TI  - Does a Consumer-Targeted Deprescribing Intervention Compromise Patient-Healthcare
      Provider Trust?
AB  - One in four community-dwelling older adults is prescribed an inappropriate
      medication. Educational interventions aimed at patients to reduce inappropriate
      medications may cause patients to question their prescriber&rsquo;s judgment. The
      objective of this study was to determine whether a patient-focused deprescribing
      intervention compromised trust between older adults and their healthcare
      providers. An educational brochure was distributed to community-dwelling older
      adults by community pharmacists in order to trigger deprescribing conversations.
      At baseline and 6-months post-intervention, participants completed the Primary
      Care Assessment Survey, which measures patient trust in doctors and pharmacists.
      Changes in trust were ascertained post-intervention. Proportions with 95%
      confidence intervals (CI), and logistic regression were used to determine a shift
      in trust and associated predictors. 352 participants responded to the
      questionnaire at both time points. The majority of participants had no change or
      gained trust in their doctors for items related to the choice of medical care
      (78.5%, 95% CI = 74.2&ndash;82.8), communication transparency (75.4%, 95% CI =
      70.7&ndash;79.8), and overall trust (81.9%, 95% CI = 77.9&ndash;86.0). Similar
      results were obtained for participants&rsquo; perceptions of their pharmacists,
      with trust remaining intact for items related to the choice of medical care
      (79.4%, 95% CI = 75.3&ndash;83.9), transparency in communicating (82.0%, 95% CI =
      78.0&ndash;86.1), and overall trust (81.6%, 95% CI = 77.5&ndash;85.7). Neither
      age, sex nor the medication class targeted for deprescribing was associated with
      a loss of trust. Overall, the results indicate that patient-focused deprescribing
      interventions do not shift patients&rsquo; trust in their healthcare providers in
      a negative direction.

PMID- 29659489
TI  - Characterizing Depression Issues on Sina Weibo.
AB  - The prevalence of depression has increased significantly over the past few years
      both in developed and developing countries. However, many people with symptoms of
      depression still remain untreated or undiagnosed. Social media may be a tool to
      help researchers and clinicians to identify and support individuals who
      experience depression. More than 394,000,000 postings were collected from China's
      most popular social media website, Sina Weibo. 1000 randomly selected depression
      related postings was coded and analyzed to learn the themes of these postings,
      and a text classifier was built to identify the postings indicating depression.
      The identified depressed users were compared with the general population on
      demographic characteristics, diurnal patterns, and patterns of emoticon usage. We
      found that disclosure of depression was the most popular theme; depression
      displayers were more engaged with social media compared to non-depression
      displayers, the depression postings showed geographical variations, depression
      displayers tended to be active during periods of leisure and sleep, and
      depression displayers used negative emoticons more frequently than non-depression
      displayers. This study offers a broad picture of depression references on China's
      social media, which may be cost effectively developed to detect and help
      individuals who may suffer from depression disorders.

PMID- 29659490
TI  - A Comparative Genomic Survey Provides Novel Insights into Molecular Evolution of
      l-Aromatic Amino Acid Decarboxylase in Vertebrates.
AB  - Melatonin is a pleiotropic molecule with various important physiological roles in
      vertebrates. l-aromatic amino acid decarboxylase (AAAD) is the second enzyme for
      melatonin synthesis. By far, a clear-cut gene function of AAAD in the
      biosynthesis of melatonin has been unclear in vertebrates. Here, we provide novel
      insights into the evolution of AAAD based on 77 vertebrate genomes. According to
      our genome-wide alignments, we extracted a total of 151 aaad nucleotide
      sequences. A phylogenetic tree was constructed on the basis of these sequences
      and corresponding protein alignments, indicating that tetrapods and diploid bony
      fish genomes contained one aaad gene and a new aaad-like gene, which formed a
      novel AAAD family. However, in tetraploid teleosts, there were two copies of the
      aaad gene due to whole genome duplication. A subsequent synteny analysis
      investigated 81 aaad sequences and revealed their collinearity and systematic
      evolution. Interestingly, we discovered that platypus (Ornithorhynchus anatinus),
      Atlantic cod (Guadus morhua), Mexican tetra (Astyanax mexicanus), and a
      Sinocyclocheilus cavefish (S. anshuiensis) have long evolutionary branches in the
      phylogenetic topology. We also performed pseudogene identification and selection
      pressure analysis; however, the results revealed a deletion of 37 amino acids in
      Atlantic cod and premature stop codons in the cave-restricted S. anshuiensis and
      A. mexicanus, suggesting weakening or disappearing rhythms in these cavefishes.
      Selective pressure analysis of aaad between platypus and other tetrapods showed
      that rates of nonsynonymous (Ka) and synonymous (Ks) substitutions were higher
      when comparing the platypus to other representative tetrapods, indicating that,
      in this semiaquatic mammal, the aaad gene experienced selection during the
      process of evolution. In summary, our current work provides novel insights into
      aaad genes in vertebrates from a genome-wide view.

PMID- 29659492
TI  - Comparative Analysis of Warp Function for Digital Image Correlation-Based
      Accurate Single-Shot 3D Shape Measurement.
AB  - Digital image correlation (DIC)-based stereo 3D shape measurement is a kind of
      single-shot method, which can achieve high precision and is robust to vibration
      as well as environment noise. The efficiency of DIC has been greatly improved
      with the proposal of inverse compositional Gauss-Newton (IC-GN) operators for
      both first-order and second-order warp functions. Without the algorithm itself,
      both the registration accuracy and efficiency of DIC-based stereo matching for
      shapes with different complexities are closely related to the selection of warp
      function, subset size, and convergence criteria. Understanding the similarity and
      difference of the impacts of prescribed subset size and convergence criteria on
      first-order and second-order warp functions, and how to choose a proper warp
      function and set optimal subset size as well as convergence criteria for
      different shapes are fundamental problems in realizing efficient and accurate 3D
      shape measurement. In this work, we present a comparative analysis of first-order
      and second-order warp functions for DIC-based 3D shape measurement using IC-GN
      algorithm. The effects of subset size and convergence criteria of first-order and
      second-order warp functions on the accuracy and efficiency of DIC are
      comparatively examined with both simulation tests and real experiments. Reference
      standards for the selection of warp function for different kinds of 3D shape
      measurement and the setting of proper convergence criteria are recommended. The
      effects of subset size on the measuring precision using different warp functions
      are also concluded.

PMID- 29659491
TI  - Antivenom Production against Bothrops jararaca and Bothrops erythromelas Snake
      Venoms Using Cross-Linked Chitosan Nanoparticles as an Immunoadjuvant.
AB  - In Brazil, envenomation by snakes of the genus Bothrops is clinically relevant,
      particularly for the species Bothrops jararaca and B. erythromelas. The most
      effective treatment for envenomation by snakes is the administration of
      antivenoms associated with adjuvants. Novel adjuvants are required to reduce side
      effects and maximize the efficiency of conventional serum and vaccine
      formulations. The polymer chitosan has been shown to have immunoadjuvant
      properties, and it has been used as a platform for delivery systems. In this
      context, we evaluated the potential immunoadjuvant properties of chitosan
      nanoparticles (CNPs) loaded with B. jararaca and B. erythromelas venoms in the
      production of sera against these venoms. Stable CNPs were obtained by ionic
      gelation, and mice were immunized subcutaneously for 6 weeks with 100 &micro;L of
      each snake venom at concentrations of 5.0 or 10.0% (w/w), encapsulated in CNPs or
      associated with aluminium hydroxide (AH). The evaluation of protein interactions
      with the CNPs revealed their ability to induce antibody levels equivalent to
      those of AH, even with smaller doses of antigen. In addition, the CNPs were less
      inflammatory due to their modified release of proteins. CNPs provide a promising
      approach for peptide/protein delivery from snake venom and will be useful for new
      vaccines.

PMID- 29659493
TI  - Cloning, Characterization, and Functional Investigation of VaHAESA from Vitis
      amurensis Inoculated with Plasmopara viticola.
AB  - Plant pattern recognition receptors (PRRs) are essential for immune responses and
      establishing symbiosis. Plants detect invaders via the recognition of pathogen
      associated molecular patterns (PAMPs) by PRRs. This phenomenon is termed PAMP
      triggered immunity (PTI). We investigated disease resistance in Vitis amurensis
      to identify PRRs that are important for resistance against downy mildew, analyzed
      the PRRs that were upregulated by incompatible Plasmopara viticola infection, and
      cloned the full-length cDNA of the VaHAESA gene. We then analyzed the structure,
      subcellular localization, and relative disease resistance of VaHAESA. VaHAESA and
      PRR-receptor-like kinase 5 (RLK5) are highly similar, belonging to the leucine
      rich repeat (LRR)-RLK family and localizing to the plasma membrane. The
      expression of PRR genes changed after the inoculation of V. amurensis with
      compatible and incompatible P. viticola; during early disease development,
      transiently transformed V. vinifera plants expressing VaHAESA were more resistant
      to pathogens than those transformed with the empty vector and untransformed
      controls, potentially due to increased H2O2, NO, and callose levels in the
      transformants. Furthermore, transgenic Arabidopsis thaliana showed upregulated
      expression of genes related to the PTI pathway and improved disease resistance.
      These results show that VaHAESA is a positive regulator of resistance against
      downy mildew in grapevines.

PMID- 29659494
TI  - Deep Brain Stimulation of the Subthalamic Nucleus in Patients with Parkinson
      Disease with Prior Pallidotomy or Thalamotomy.
AB  - Objective. To evaluate the efficacy of deep brain stimulation of the subthalamic
      nucleus (STN DBS) in patients with Parkinson disease (PD) who previously
      underwent lesioning of the basal ganglia. Material and methods. The study
      included 22 patients who underwent STN DBS. Eleven patients had undergone prior
      unilateral pallidotomy (n = 6) or VL/VIM thalamotomy (n = 5) while the other 11
      patients had not. The primary outcome was the change from baseline in the motor
      subscore of the Unified Parkinson Disease Rating Scale (UPDRS-III) 12 months
      after STN DBS. Secondary outcomes included change in motor response complications
      (UPDRS-IV) and change in levodopa equivalent daily dose (LEDD). Results. In the
      group with prior lesioning UPDRS-III improved by 45%, from 51.5 &plusmn; 9.0%
      (range, 35&ndash;65) to 26.5 &plusmn; 8.4 (range, 21&ndash;50) (p < 0.01) and
      UPDRS-IV by 75%, from 8.0 &plusmn; 2.01 (range, 5&ndash;11) to 2.1 &plusmn; 0.74
      (range, 1&ndash;3) (p < 0.01). In the group without prior lesioning UPDRS-III
      improved by 61%, from 74.2% &plusmn; 7.32 (range, 63&ndash;82) to 29.3 &plusmn;
      5.99 (range, 20&ndash;42) (p < 0.01) and UPDRS-IV by 77%, from 9.1 &plusmn; 2.46
      (range, 5&ndash;12) to 2.0 &plusmn; 1.1 (range, 1&ndash;4) (p < 0.01). Comparing
      the two groups (with and without lesioning) no significant differences were found
      either in UPDRS-III (p > 0.05) or UPDRS-IV scores (p > 0.05) at 12 months post
      DBS. The LEDD was reduced by 51.4%, from 1008.2 &plusmn; 346.4 to 490.0 &plusmn;
      194.3 in those with prior surgery (p < 0.01) and by 55.0%, from 963.4 &plusmn;
      96.2 to 433.3 &plusmn; 160.2 in those without (p < 0.01).UPDRS-III improved by
      51.8%, from 53.7 &plusmn; 4.6 (range, 50&ndash;62) to 25.0 &plusmn; 3.8 (range,
      21&ndash;31) in those with prior pallidotomy (p < 0.01), and by 37.5%, from 48.8
      &plusmn; 12.6 (range, 35&ndash;65) to 29.8 &plusmn; 13.6 (range, 22&ndash;50) in
      those with prior thalamotomy (p < 0.01). This numerical difference in improvement
      was not statistically significant (p > 0.05). Conclusion. Our comparative study
      indicates that bilateral STN DBS is effective and can be used in patients with
      Parkinson disease with prior unilateral stereotactic destructive operations on
      subcortical structures. The results in our patient cohort are generally
      consistent with previously published reports of smaller series from multiple
      centers worldwide.

PMID- 29659495
TI  - Transient Recombinant Protein Production in Glycoengineered Nicotiana benthamiana
      Cell Suspension Culture.
AB  - Transient recombinant protein production is a promising alternative to stable
      transgenic systems, particularly for emergency situations in which rapid
      production of novel therapeutics is needed. In plants, Agrobacterium tumefaciens
      can be used as a gene delivery vector for transient expression. A potential
      barrier for plant-based production of human therapeutics is that different
      glycosylation patterns are found on plant and mammalian proteins. Since
      glycosylation can affect the efficacy, safety and stability of a therapeutic
      protein, methods to control glycan structures and distributions in plant-based
      systems would be beneficial. In these studies, we performed Agrobacterium
      mediated transient expression in glycoengineered plant cell suspension cultures.
      To reduce the presence of plant-specific glycans on the product, we generated and
      characterized cell suspension cultures from &beta;-1,2-xylosyltransferase and
      &alpha;-1,3-fucosyltransferase knockdown Nicotiana benthamiana. An anthrax decoy
      fusion protein was transiently produced in these glycoengineered plant cell
      suspension cultures through co-culture with genetically engineered Agrobacterium.
      The mass ratio of Agrobacterium to plant cells used was shown to impact
      recombinant protein expression levels. N-glycosylation analysis on the anthrax
      decoy fusion protein produced in glycoengineered N. benthamiana showed a dramatic
      reduction in plant-specific N-glycans. Overall, the results presented here
      demonstrate the feasibility of a simple, rapid and scalable process for transient
      production of recombinant proteins without plant-specific glycans in a
      glycoengineered plant cell culture host.

PMID- 29659497
TI  - Nutritional Combined Greenhouse Gas Life Cycle Analysis for Incorporating
      Canadian Yellow Pea into Cereal-Based Food Products.
AB  - Incorporating low cost pulses, such as yellow peas, that are rich in nutrients
      and low in fertilizer requirements, into daily food items, can improve the
      nutritional and sustainability profile of national diets. This paper
      systematically characterized the effect of using Canadian grown whole yellow pea
      and refined wheat flours on nutritional density and carbon footprint in cereal
      based food products. Canada-specific production data and the levels of 27 macro-
      and micronutrients were used to calculate the carbon footprint and nutrient
      balance score (NBS), respectively, for traditional and reformulated pan bread,
      breakfast cereal, and pasta. Results showed that partial replacement of refined
      wheat flour with yellow pea flour increased the NBS of pan bread, breakfast
      cereal, and pasta by 11%, 70%, and 18%, and decreased the life cycle carbon
      footprint (kg CO2 eq/kg) by 4%, 11%, and 13%, respectively. The cultivation stage
      of wheat and yellow peas, and the electricity used during the manufacturing stage
      of food production, were the hotspots in the life cycle. The nutritional and
      greenhouse gas (GHG) data were combined as the nutrition carbon footprint score
      (NCFS) (NBS/g CO2 per serving), a novel indicator that reflects product-level
      nutritional quality per unit environmental impact. Results showed that yellow pea
      flour increased the NCFS by 15% for pan bread, 90% for breakfast cereal, and 35%
      for pasta. The results and framework of this study are relevant for food
      industry, consumers, as well as global and national policy-makers evaluating the
      effect of dietary change and food reformulation on nutritional and climate change
      targets.

PMID- 29659496
TI  - Synthesis of Theaflavins and Their Functions.
AB  - Numerous epidemiological and interventional clinical studies have consistently
      reported that black tea is good for human health. The polyphenolic compound,
      theaflavin, and its galloyl esters (theaflavins) are the primary red pigments in
      black tea that possess several health benefits, including fat-reducing and
      glucose-lowering capabilities and lifestyle-related disease prevention related to
      anti-obesity, anticancer, anti-atherosclerotic, anti-inflammatory, antiviral,
      antibacterial, anti-osteoporotic, and anti-dental caries properties. These
      compounds are produced by key enzymes, such as polyphenol oxidase and peroxidase,
      from parent green tea catechins present in fresh green tea leaves during the
      production of black tea leaves or the fermentation of green tea. However,
      theaflavins are only present in low concentrations in black tea; thus, their
      extraction from black tea leaves at sufficient levels for use in medical studies
      has been difficult. To circumvent this issue, different procedures for the
      synthesis of theaflavins using chemical oxidizing reagents or enzymes have been
      studied; however, low yields have limited their utility. Recently, however,
      several biosynthetic methods have been developed for the mass production of
      theaflavins. Using these methods, the physiological functions of theaflavins in
      lifestyle-related diseases in mice and humans have also been studied. In this
      review, we present the synthesis of theaflavins and their health benefits.

PMID- 29659498
TI  - MicroRNAs Targeting Caspase-3 and -7 in PANC-1 Cells.
AB  - MicroRNAs (miRNAs), a critical part of the RNA silencing machinery, are known to
      play important regulatory roles in cancer. However, the consequence of miRNA
      deregulation in cancer is unknown for many miRNAs. Here, we define that miRNAs,
      miR-17-5p, miR-132-3p/-212-3p, and miR-337-3p are significantly up-regulated in
      the pancreatic ductal adenocarcinomas (PDAC) compared to the normal and benign
      tissues. Furthermore, by using PANC-1 cells, we demonstrate that overexpressed
      miR-337-3p and miR-17-5p/miR-132-3p/-212-3p can regulate executioner caspases-3
      and -7, respectively. In addition, over-expression of miRNAs, especially miR-337
      3p, attenuates tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)
      cytotoxicity in PANC-1 cells. Our findings unveil an important biological
      function for miRNAs up-regulated in PDAC in coordinately regulating caspases,
      potentially contributing to the malignant progression of PDAC.

PMID- 29659499
TI  - Study on the Coupling Mechanism of the Orthogonal Dipoles with Surface Plasmon in
      Green LED by Cathodoluminescence.
AB  - We analyzed the coupling behavior between the localized surface plasmon (LSP) and
      quantum wells (QWs) using cathodoluminescence (CL) in a green light-emitting
      diodes (LED) with Ag nanoparticles (NPs) filled in photonic crystal (PhC) holes.
      Photoluminescence (PL) suppression and CL enhancement were obtained for the same
      green LED sample with the Ag NP array. Time-resolved PL (TRPL) results indicate
      strong coupling between the LSP and the QWs. Three-dimensional (3D) finite
      difference time domain (FDTD) simulation was performed using a three-body model
      consisting of two orthogonal dipoles and a single Ag NP. The LSP&ndash;QWs
      coupling effect was separated from the electron-beam (e-beam)&ndash;LSP&ndash;QW
      system by linear approximation. The energy dissipation was significantly reduced
      by the z-dipole introduction under the e-beam excitation. In this paper, the
      coupling mechanism is discussed and a novel emission structure is proposed.

PMID- 29659500
TI  - A Facile Approach to Prepare Black TiO2 with Oxygen Vacancy for Enhancing
      Photocatalytic Activity.
AB  - Black TiO2 has triggered worldwide research interest due to its excellent
      photocatalytic properties. However, the understanding of its
      structure&ndash;property relationships and a more effective, facile and versatile
      method to produce it remain great challenges. We have developed a facile approach
      to synthesize black TiO2 nanoparticles with significantly improved light
      absorption in the visible and infrared regions. The experimental results show
      that oxygen vacancies are the major factors responsible for black coloration.
      More importantly, our black TiO2 nanoparticles have no Ti3+ ions. These oxygen
      vacancies could introduce localized states in the bandgap and act as trap
      centers, significantly decreasing the electron&ndash;hole recombination. The
      photocatalytic decomposition of both rhodamine B and methylene blue demonstrated
      that, under ultraviolet light irradiation, better photocatalytic performance is
      achieved with our black TiO2 nanoparticles than with commercial TiO2
      nanoparticles.

PMID- 29659501
TI  - The Stability of Medicinal Plant microRNAs in the Herb Preparation Process.
AB  - Herbal medicine is now globally accepted as a valid alternative system of
      pharmaceutical therapies. Various studies around the world have been initiated to
      develop scientific evidence-based herbal therapies. Recently, the therapeutic
      potential of medicinal plant derived miRNAs has attracted great attraction.
      MicroRNAs have been indicated as new bioactive ingredients in medicinal plants.
      However, the stability of miRNAs during the herbal preparation process and their
      bioavailability in humans remain unclear. Viscum album L. (European mistletoe)
      has been widely used in folk medicine for the treatment of cancer and
      cardiovascular diseases. Our previous study has indicated the therapeutic
      potential of mistletoe miRNAs by using bioinformatics tools. To evaluate the
      stability of these miRNAs, various mistletoe extracts that mimic the clinical
      medicinal use as well as traditional folk medicinal use were prepared. The
      mistletoe miRNAs including miR166a-3p, miR159a, miR831-5p, val-miR218 and val
      miR11 were quantified by stem-loop qRT-PCR. As a result, miRNAs were detectable
      in the majority of the extracts, indicating that consumption of medicinal plant
      preparations might introduce miRNAs into mammals. The factors that might cause
      miRNA degradation include ultrasonic treatment, extreme heat, especially RNase
      treatment, while to be associated with plant molecules (e.g., proteins, exosomes)
      might be an efficient way to protect miRNAs against degradation. Our study
      confirmed the stability of plant derived miRNAs during herb preparations,
      suggesting the possibility of functionally intact medicinal plant miRNAs in
      mammals.

PMID- 29659502
TI  - First Detection of the CTXM-15 Producing Escherichia coli O25-ST131 Pandemic
      Clone in Ecuador.
AB  - Our aim was identify of the pandemic B2-ST131 Escherichia coli clone by to the
      Institute Pasteur and Achtman scheme, and investigate the resistance profile
      phenotypic-genotypic, with identification of class 1 integron. Of thirty-five
      ESBL-producing isolates recovered of patients with diagnosis of urinary tract
      infections (UTI), six E. coli strains serotype O25 were identified with
      resistance antimicrobial to several groups of antibiotics such as broad-spectrum
      cephalosporins, fluoroquinolones and aminoglycosides, harboring blaSHV, blaCTX-M
      genes in all isolates and blaTEM in two isolates. Sequencing of blaCTX-M revealed
      CTX-M-15 in all strains. The PMQR aac(6&acute;)-Ib-cr and qnrB19 genes were
      presented in five and four isolates respectively, AMEs genes aac(6&acute;)-Ib and
      aac(3)-IIa were presented in strain amikacin-gentamicin-resistant. Sequencing of
      the variable regions of the class 1 integron revealed dfrA and aadA genes
      cassette. The analysis of multilocus sequence typing (MLST) confirms the presence
      of the pandemic B2-ST131 E. coli clone by Achtman scheme in all ST43 isolates
      obtained by of the Institute Pasteur scheme. The results presented herein, reveal
      the presence of B2-ST131 E. coli clone in Ecuador, disseminated in hospitals and
      community settings.

PMID- 29659504
TI  - Microstructure and Mechanical Properties of Graphene-Reinforced Titanium
      Matrix/Nano-Hydroxyapatite Nanocomposites.
AB  - Biomaterial composites made of titanium and hydroxyapatite (HA) powder are among
      the most important biomedicalmaterials due to their good mechanical properties
      and biocompatibility. In this work, graphene-reinforced titanium matrix/nano
      hydroxyapatite nanocomposites were prepared by vacuum hot-pressing sintering. The
      microstructure and mechanical properties of graphene-reinforced titanium
      matrix/nano-hydroxyapatite nanocomposites with different graphene content were
      systematically investigated. Microstructures of the nanocomposites were examined
      by X-ray diffraction (XRD), back scattered electron imaging (BSE), scanning
      electron microscope (SEM) equipped with energy dispersive spectrometer (EDS),
      electron probe microanalyzer (EPMA), and transmission electron microscope (TEM).
      The mechanical properties were determined from microhardness, shear strength, and
      compressive strength. Results showed that during the high-temperature sintering
      process, complex chemical reactions occurred, resulting in new phases of
      nucleation such as Ca3(PO4)2, TixPy, and Ti3O.The new phases, which easily
      dropped off under the action of external force, could hinder the densification of
      sintering and increase the brittleness of the nanocomposites. Results
      demonstrated that graphene had an impact on the microstructure and mechanical
      properties of the nanocomposites. Based on the mechanical properties and
      microstructure of the nanocomposites, the strengthening and fracture mechanisms
      of the graphene-reinforced titanium matrix/nano-hydroxyapatite nanocomposites
      with different graphene content were analyzed.

PMID- 29659503
TI  - Tribute to Marcelle Grenson (1925-1996), A Pioneer in the Study of Amino Acid
      Transport in Yeast.
AB  - The year 2016 marked the 20th anniversary of the death of Marcelle Grenson and
      the 50th anniversary of her first publication on yeast amino acid transport, the
      topic to which, as Professor at the Free University of Brussels (ULB), she
      devoted the major part of her scientific career. M. Grenson was the first
      scientist in Belgium to introduce and apply genetic analysis in yeast to dissect
      the molecular mechanisms that were underlying complex problems in biology. Today,
      M. Grenson is recognized for the pioneering character of her work on the
      diversity and regulation of amino acid transporters in yeast. The aim of this
      tribute is to review the major milestones of her forty years of scientific
      research that were conducted between 1950 and 1990.

PMID- 29659505
TI  - NF-kappaB Signaling Regulates Epstein-Barr Virus BamHI-Q-Driven EBNA1 Expression.
AB  - Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) is one of the few viral
      proteins expressed by EBV in nasopharyngeal carcinoma (NPC), most likely because
      of its essential role in maintaining the viral genome in EBV-infected cells. In
      NPC, EBNA1 expression is driven by the BamHI-Q promoter (Qp), which is regulated
      by both cellular and viral factors. We previously determined that the expression
      of another group of EBV transcripts, BamHI-A rightward transcripts (BARTs), is
      associated with constitutively activated nuclear factor-kappaB (NF-kappaB)
      signaling in NPC cells. Here, we show that, like the EBV BART promoter, the EBV
      Qp also responds to NF-kappaB signaling. NF-kappaB p65, but not p50, can activate
      Qp in vitro, and NF-kappaB signaling regulates Qp-EBNA1 expression in NPC cells,
      as well as in other EBV-infected epithelial cells. The introduction of mutations
      in the putative NF-kappaB site reduced Qp activation by the NF-kappaB p65
      subunit. Binding of p65 to Qp was shown by chromatin immunoprecipitation (ChIP)
      analysis, while electrophoretic mobility shift assays (EMSAs) demonstrated that
      p50 can also bind to Qp. Inhibition of NF-kappaB signaling by the IkappaB kinase
      inhibitor PS-1145 resulted in the downregulation of Qp-EBNA1 expression in C666-1
      NPC cells. Since EBNA1 has been reported to block p65 activation by inhibiting
      IKKalpha/beta through an unknown mechanism, we suggest that, in NPC, NF-kappaB
      signaling and EBNA1 may form a regulatory loop which supports EBV latent gene
      expression, while also limiting NF-kappaB activity. These findings emphasize the
      role of NF-kappaB signaling in the regulation of EBV latency in EBV-associated
      tumors.

PMID- 29659506
TI  - In Vitro Inhibitory Effects of Synthetic Cannabinoid EAM-2201 on Cytochrome P450
      and UDP-Glucuronosyltransferase Enzyme Activities in Human Liver Microsomes.
AB  - EAM-2201, a synthetic cannabinoid, is a potent agonist of the cannabinoid
      receptors that is widely abused as an illicit recreational drug in combination
      with other drugs. To evaluate the potential of EAM-2201 as a perpetrator of
      drug&ndash;drug interactions, the inhibitory effects of EAM-2201 on major drug
      metabolizing enzymes, cytochrome P450s (CYPs) and uridine 5&prime;-diphospho
      glucuronosyltransferases (UGTs) were evaluated in pooled human liver microsomes
      using liquid chromatography&ndash;tandem mass spectrometry (LC-MS/MS). EAM-2201
      at doses up to 50 &micro;M negligibly inhibited the activities of eight major
      human CYPs (1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6 and 3A4) and five UGTs (1A1, 1A4,
      1A6, 1A9 and 2B7) in human liver microsomes. EAM-2201 exhibited time-dependent
      inhibition of CYP2C8-catalyzed amodiaquine N-deethylation, CYP2C9-catalyzed
      diclofenac 4&prime;-hydroxylation, CYP2C19-catalyzed [S]-mephenytoin 4&prime;
      hydroxylation and CYP3A4-catalyzed midazolam 1&prime;-hydroxylation with Ki
      values of 0.54 &micro;M (kinact: 0.0633 min&minus;1), 3.0 &micro;M (kinact:
      0.0462 min&minus;1), 3.8 &micro;M (kinact: 0.0264 min&minus;1) and 4.1 &micro;M
      (kinact: 0.0250 min&minus;1), respectively and competitively inhibited UGT1A3
      catalyzed chenodeoxycholic acid 24-acyl-glucuronidation, with a Ki value of 2.4
      &micro;M. Based on these in vitro results, we conclude that EAM-2201 has the
      potential to trigger in vivo pharmacokinetic drug interactions when co
      administered with substrates of CYP2C8, CYP2C9, CYP2C19, CYP3A4 and UGT1A3.

PMID- 29659507
TI  - Customized Peptide Biomaterial Synthesis via an Environment-Reliant Auto
      Programmer Stigmergic Approach.
AB  - Stigmergy, a form of self-organization, was employed here to engineer a self
      organizing peptide capable of forming a nano- or micro-structure and that can
      potentially be used in various drug delivery and biomedical applications. These
      self-assembling peptides exhibit several desirable qualities for drug delivery,
      tissue engineering, cosmetics, antibiotics, food science, and biomedical surface
      engineering. In this study, peptide biomaterial synthesis was carried out using
      an environment-reliant auto-programmer stigmergic approach. A model protein,
      &alpha;-gliadin (31, 36, and 38 kD), was forced to attain a primary structure
      with free &ndash;SH groups and broken down enzymatically into smaller fragments
      using chymotrypsin. This breakdown was carried out at different environment
      conditions (37 and 50 &deg;C), and the fragments were allowed to self-organize at
      these temperatures. The new peptides so formed diverged according to the
      environmental conditions. Interestingly, two peptides (with molecular weights of
      13.8 and 11.8 kD) were isolated when the reaction temperature was maintained at
      50 &deg;C, while four peptides with molecular weights of 54, 51, 13.8, and 12.8
      kD were obtained when the reaction was conducted at 37 &deg;C. Thus, at a higher
      temperature (50 &deg;C), the peptides formed, compared to the original protein,
      had lower molecular weights, whereas, at a lower temperature (37 &deg;C), two
      peptides had higher molecular weights and two had lower molecular weights.

PMID- 29659508
TI  - Escalator: An Autonomous Scheduling Scheme for Convergecast in TSCH.
AB  - Time Slotted Channel Hopping (TSCH) is widely used in the industrial wireless
      sensor networks due to its high reliability and energy efficiency. Various
      timeslot and channel scheduling schemes have been proposed for achieving high
      reliability and energy efficiency for TSCH networks. Recently proposed autonomous
      scheduling schemes provide flexible timeslot scheduling based on the routing
      topology, but do not take into account the network traffic and packet forwarding
      delays. In this paper, we propose an autonomous scheduling scheme for
      convergecast in TSCH networks with RPL as a routing protocol, named Escalator.
      Escalator generates a consecutive timeslot schedule along the packet forwarding
      path to minimize the packet transmission delay. The schedule is generated
      autonomously by utilizing only the local routing topology information without any
      additional signaling with other nodes. The generated schedule is guaranteed to be
      conflict-free, in that all nodes in the network could transmit packets to the
      sink in every slotframe cycle. We implement Escalator and evaluate its
      performance with existing autonomous scheduling schemes through a testbed and
      simulation. Experimental results show that the proposed Escalator has lower end
      to-end delay and higher packet delivery ratio compared to the existing schemes
      regardless of the network topology.

PMID- 29659509
TI  - Antartin, a Cytotoxic Zizaane-Type Sesquiterpenoid from a Streptomyces sp.
      Isolated from an Antarctic Marine Sediment.
AB  - Antartin (1), a new zizaane-type sesquiterpene, was isolated from Streptomyces
      sp. SCO736. The chemical structure of 1 was assigned from the interpretation of
      1D and 2D NMR in addition to mass spectrometric data. The relative
      stereochemistry of 1 was determined by analysis of NOE data, while the absolute
      stereochemistry was decided based on a comparison of experimental and calculated
      electronic circular dichroism (ECD) spectra. Antartin (1) showed cytotoxicity
      against A549, H1299, and U87 cancer cell lines by causing cell cycle arrest at
      the G1 phase.

PMID- 29659510
TI  - Multi-Fault Diagnosis of Rolling Bearings via Adaptive Projection Intrinsically
      Transformed Multivariate Empirical Mode Decomposition and High Order Singular
      Value Decomposition.
AB  - Rolling bearings are important components in rotary machinery systems. In the
      field of multi-fault diagnosis of rolling bearings, the vibration signal
      collected from single channels tends to miss some fault characteristic
      information. Using multiple sensors to collect signals at different locations on
      the machine to obtain multivariate signal can remedy this problem. The adverse
      effect of a power imbalance between the various channels is inevitable, and
      unfavorable for multivariate signal processing. As a useful, multivariate signal
      processing method, Adaptive-projection has intrinsically transformed multivariate
      empirical mode decomposition (APIT-MEMD), and exhibits better performance than
      MEMD by adopting adaptive projection strategy in order to alleviate power
      imbalances. The filter bank properties of APIT-MEMD are also adopted to enable
      more accurate and stable intrinsic mode functions (IMFs), and to ease mode mixing
      problems in multi-fault frequency extractions. By aligning IMF sets into a third
      order tensor, high order singular value decomposition (HOSVD) can be employed to
      estimate the fault number. The fault correlation factor (FCF) analysis is used to
      conduct correlation analysis, in order to determine effective IMFs; the
      characteristic frequencies of multi-faults can then be extracted. Numerical
      simulations and the application of multi-fault situation can demonstrate that the
      proposed method is promising in multi-fault diagnoses of multivariate rolling
      bearing signal.

PMID- 29659511
TI  - Quorum Sensing and Quorum Quenching in Agrobacterium: A "Go/No Go System"?
AB  - The pathogen Agrobacterium induces gall formation on a wide range of
      dicotyledonous plants. In this bacteria, most pathogenicity determinants are
      borne on the tumour inducing (Ti) plasmid. The conjugative transfer of this
      plasmid between agrobacteria is regulated by quorum sensing (QS). However,
      processes involved in the disturbance of QS also occur in this bacteria under the
      molecular form of a protein, TraM, inhibiting the sensing of the QS signals, and
      two lactonases BlcC (AttM) and AiiB that degrade the acylhomoserine lactone (AHL)
      QS signal. In the model Agrobacteriumfabrum strain C58, several data, once
      integrated, strongly suggest that the QS regulation may not be reacting only to
      cell concentration. Rather, these QS elements in association with the quorum
      quenching (QQ) activities may constitute an integrated and complex &ldquo;go/no
      go system&rdquo; that finely controls the biologically costly transfer of the Ti
      plasmid in response to multiple environmental cues. This decision mechanism
      permits the bacteria to sense whether it is in a gall or not, in a living or
      decaying tumor, in stressed plant tissues, etc. In this scheme, the role of the
      lactonases selected and maintained in the course of Ti plasmid and agrobacterial
      evolution appears to be pivotal.

PMID- 29659512
TI  - A Universal Vacant Parking Slot Recognition System Using Sensors Mounted on Off
      the-Shelf Vehicles.
AB  - An automatic parking system is an essential part of autonomous driving, and it
      starts by recognizing vacant parking spaces. This paper proposes a method that
      can recognize various types of parking slot markings in a variety of lighting
      conditions including daytime, nighttime, and underground. The proposed method can
      readily be commercialized since it uses only those sensors already mounted on off
      the-shelf vehicles: an around-view monitor (AVM) system, ultrasonic sensors, and
      in-vehicle motion sensors. This method first detects separating lines by
      extracting parallel line pairs from AVM images. Parking slot candidates are
      generated by pairing separating lines based on the geometric constraints of the
      parking slot. These candidates are confirmed by recognizing their entrance
      positions using line and corner features and classifying their occupancies using
      ultrasonic sensors. For more reliable recognition, this method uses the
      separating lines and parking slots not only found in the current image but also
      found in previous images by tracking their positions using the in-vehicle motion
      sensor-based vehicle odometry. The proposed method was quantitatively evaluated
      using a dataset obtained during the day, night, and underground, and it
      outperformed previous methods by showing a 95.24% recall and a 97.64% precision.

PMID- 29659514
TI  - Coronial Practice, Indigeneity and Suicide.
AB  - All available data suggest that, like many other Indigenous peoples, Australian
      Aborigines are significantly more likely to kill themselves than are non
      Aboriginal Australians. This statistical disparity is normally positioned an
      objective, ontological and undeniable social fact, a fact best explained as a
      function of endemic community disadvantage and disenfranchisement. This research
      explores the possibility that higher-than-normal Aboriginal suicide rates may
      also be a function of coronial decision-making practices. Based upon in-depth
      interviews with 32 coroners from across Australia, the following conclusions
      emerged from the data. First, coroners have differing perceptions of Indigenous
      capacity, and are less likely to have concerns about intent when the suicide is
      committed by an Indigenous person. Second, coroners have identified divergent
      scripts of Indigenous suicide, particularly its spontaneity and public location,
      and this supports rather than challenges, a finding of suicide. Third, the
      coronial perception of Indigenous life is a factor which influences a suicide
      determination for Indigenous deaths. Finally, the low level of Indigenous
      engagement with the coronial system, and the unlikelihood of a challenge to the
      finding of suicide by Indigenous families, means that a coronial determination of
      suicide is more likely.

PMID- 29659513
TI  - Chromatin Architectural Changes during Cellular Senescence and Aging.
AB  - Chromatin 3D structure is highly dynamic and associated with many biological
      processes, such as cell cycle progression, cellular differentiation, cell fate
      reprogramming, cancer development, cellular senescence, and aging. Recently, by
      using chromosome conformation capture technologies, tremendous findings have been
      reported about the dynamics of genome architecture, their associated proteins,
      and the underlying mechanisms involved in regulating chromatin spatial
      organization and gene expression. Cellular senescence and aging, which involve
      multiple cellular and molecular functional declines, also undergo significant
      chromatin structural changes, including alternations of heterochromatin and
      disruption of higher-order chromatin structure. In this review, we summarize
      recent findings related to genome architecture, factors regulating chromatin
      spatial organization, and how they change during cellular senescence and aging.

PMID- 29659515
TI  - Can Zymomonas mobilis Substitute Saccharomyces cerevisiae in Cereal Dough
      Leavening?
AB  - Baker&rsquo;s yeast intolerance is rising among Western populations, where
      Saccharomyces cerevisiae is spread in fermented food and food components.
      Zymomonas mobilis is a bacterium commonly used in tropical areas to produce
      alcoholic beverages, and it has only rarely been considered for dough leavening
      probably because it only ferments glucose, fructose and sucrose, which are
      scarcely present in flour. However, through alcoholic fermentation, similarly to
      S. cerevisiae, it provides an equimolar mixture of ethanol and CO2 that can rise
      a dough. Here, we propose Z. mobilis as a new leavening agent, as an alternative
      to S. cerevisiae, overcoming its technological limit with different strategies:
      (1) adding glucose to the dough formulation; and (2) exploiting the maltose
      hydrolytic activity of Lactobacillus sanfranciscensis associated with Z. mobilis.
      CO2 production, dough volume increase, pH value, microbial counts, sugars
      consumption and ethanol production were monitored. Results suggest that glucose
      addition to the dough lets Z. mobilis efficiently leaven a dough, while glucose
      released by L. sanfranciscensis is not so well fermented by Z. mobilis, probably
      due to the strong acidification. Nevertheless, the use of Z. mobilis as a
      leavening agent could contribute to increasing the variety of baked goods
      alternative to those leavened by S. cerevisiae.

PMID- 29659516
TI  - "Skin-Core-Skin" Structure of Polymer Crystallization Investigated by Multiscale
      Simulation.
AB  - &ldquo;Skin-core-skin&rdquo; structure is a typical crystal morphology in
      injection products. Previous numerical works have rarely focused on crystal
      evolution; rather, they have mostly been based on the prediction of temperature
      distribution or crystallization kinetics. The aim of this work was to achieve the
      &ldquo;skin-core-skin&rdquo; structure and investigate the role of external flow
      and temperature fields on crystal morphology. Therefore, the multiscale algorithm
      was extended to the simulation of polymer crystallization in a pipe flow. The
      multiscale algorithm contains two parts: a collocated finite volume method at the
      macroscopic level and a morphological Monte Carlo method at the microscopic
      level. The SIMPLE (semi-implicit method for pressure linked equations) algorithm
      was used to calculate the polymeric model at the macroscopic level, while the
      Monte Carlo method with stochastic birth-growth process of spherulites and shish
      kebabs was used at the microscopic level. Results show that our algorithm is
      valid to predict &ldquo;skin-core-skin&rdquo; structure, and the initial melt
      temperature and the maximum velocity of melt at the inlet mainly affects the
      morphology of shish-kebabs.

PMID- 29659517
TI  - Energy Consumption Research of Mobile Data Collection Protocol for Underwater
      Nodes Using an USV.
AB  - The Unmanned Surface Vehicle (USV) integrated with an acoustic modem is a novel
      mobile vehicle for data collection, which has an advantage in terms of mobility,
      efficiency, and collection cost. In the scenario of data collection, the USV is
      controlled autonomously along the planning trajectory and the data of underwater
      nodes are dynamically collected. In order to improve the efficiency of data
      collection and extend the life of the underwater nodes, a mobile data collection
      protocol for underwater nodes using the USV was proposed. In the protocol, the
      stop-and-wait ARQ transmission mechanism is adopted, where the duty cycle is
      designed considering the ratio between the sleep mode and the detection mode, and
      the transmission ratio is defined by the duty cycle, wake-up signal cycles, and
      USV&rsquo;s speed. According to protocol, the evaluation index for energy
      consumption is constructed based on the duty cycle and the transmission ratio.
      The energy consumption of the protocol is simulated and analyzed using the mobile
      communication experiment data of USV, taking into consideration USV&rsquo;s
      speed, data sequence length, and duty cycle. Optimized protocol parameters are
      identified, which in turn denotes the proposed protocol&rsquo;s feasibility and
      effectiveness.

PMID- 29659518
TI  - Examining the Genetic Background of Porcine Muscle Growth and Development Based
      on Transcriptome and miRNAome Data.
AB  - Recently, selection in pigs has been focused on improving the lean meat content
      in carcasses; this focus has been most evident in breeds constituting a paternal
      component in breeding. Such sire-breeds are used to improve the meat quantity of
      cross-breed pig lines. However, even in one breed, a significant variation in the
      meatiness level can be observed. In the present study, the comprehensive analysis
      of genes and microRNA expression profiles in porcine muscle tissue was applied to
      identify the genetic background of meat content. The comparison was performed
      between whole gene expression and miRNA profiles of muscle tissue collected from
      two sire-line pig breeds (Pietrain, Hampshire). The RNA-seq approach allowed the
      identification of 627 and 416 differentially expressed genes (DEGs) between pig
      groups differing in terms of loin weight between Pietrain and Hampshire breeds,
      respectively. The comparison of miRNA profiles showed differential expression of
      57 microRNAs for Hampshire and 34 miRNAs for Pietrain pigs. Next, 43 genes and 18
      miRNAs were selected as differentially expressed in both breeds and potentially
      related to muscle development. According to Gene Ontology analysis, identified
      DEGs and microRNAs were involved in the regulation of the cell cycle, fatty acid
      biosynthesis and regulation of the actin cytoskeleton. The most deregulated
      pathways dependent on muscle mass were the Hippo signalling pathway connected
      with the TGF-beta signalling pathway and controlling organ size via the
      regulation of ubiquitin-mediated proteolysis, cell proliferation and apoptosis.
      The identified target genes were also involved in pathways such as the FoxO
      signalling pathway, signalling pathways regulating pluripotency of stem cells and
      the PI3K-Akt signalling pathway. The obtained results indicate molecular
      mechanisms controlling porcine muscle growth and development. Identified genes
      (SOX2, SIRT1, KLF4, PAX6 and genes belonging to the transforming growth factor
      beta superfamily) could be considered candidate genes for determining muscle mass
      in pigs.

PMID- 29659519
TI  - Temperature Variability and Gastrointestinal Infections: A Review of Impacts and
      Future Perspectives.
AB  - The objectives of this research are to review and assess the current state of
      knowledge of the association between environmental temperature and
      gastrointestinal (GI) infections. A review of the published literature was
      undertaken using standard approaches. Initially, four electronic databases
      including Embase, Medline, Scopus, and Web of Science were chosen to retrieve
      studies published from 1 January 2006 to 31 December 2017 based on selected
      keywords used in the primary search. After the elimination of duplicates, the
      titles were reviewed for relevance to the principal research question. Secondly,
      the abstracts of titles deemed to be relevant were reviewed for significance and
      finally the articles were reviewed in their entirety to identify their
      contribution to the principal research question. Initially, 8201 articles were
      identified, and eight studies finally met the inclusion criteria. A secondary
      phase involving scrutiny of the references of key identified articles found three
      further studies. Consequently, 11 papers were selected for the final review.
      Current literature confirms a significant association between temperature and
      infectious gastroenteritis worldwide. Also, a most-likely non-linear correlation
      between rainfall and GI infections has been identified in that the rate of such
      infections can be increased with either high or low precipitation. Finally, some
      studies suggest high relative humidity may not increase the rate of GI infections
      and some have found it may decrease it. These findings help inform predictions of
      risk, particularly under future climate change scenarios.

PMID- 29659520
TI  - Comparative microRNA-seq Analysis Depicts Candidate miRNAs Involved in Skin Color
      Differentiation in Red Tilapia.
AB  - Differentiation and variation in body color has been a growing limitation to the
      commercial value of red tilapia. Limited microRNA (miRNA) information is
      available on skin color differentiation and variation in fish so far. In this
      study, a high-throughput Illumina sequencing of sRNAs was conducted on three
      color varieties of red tilapia and 81,394,491 raw reads were generated. A total
      of 158 differentially expressed miRNAs (|log2(fold change)| &ge; 1 and q-value
      &le; 0.001) were identified. Target prediction and functional analysis of color
      related miRNAs showed that a variety of putative target genes&mdash;including
      slc7a11, mc1r and asip&mdash;played potential roles in pigmentation. Moreover;
      the miRNA-mRNA regulatory network was illustrated to elucidate the pigmentation
      differentiation, in which miR-138-5p and miR-722 were predicted to play important
      roles in regulating the pigmentation process. These results advance our
      understanding of the molecular mechanisms of skin pigmentation differentiation in
      red tilapia.

PMID- 29659521
TI  - Boy Smokers' Rationalisations for Engaging in Potentially Fatal Behaviour: In
      Depth Interviews in The Netherlands.
AB  - Adolescent smokers engage in cognitive rationalisation processes that lower
      perceptions of personal vulnerability to the health consequences of smoking.
      There is, however, hardly any evidence that provides in-depth insights on
      adolescents&rsquo; recurring rationalisations. Therefore, we explored how boy
      smokers deal with the knowledge that they are engaging in potentially fatal
      behaviour. Interviews were held with 16 boy smokers aged 16 to 17 years old. The
      qualitative analysis focussed on combining boys&rsquo; reasons about why they
      think they will not experience severe health consequences into coherent
      rationalisations that recurred among interviewees. Three rationalisations emerged
      from the analysis. First, boys trivialize the immediate consequences and think
      these can be compensated for and are outweighed by the benefits of smoking.
      Second, boys assume that smoking will only take place during adolescence and they
      will, therefore, recover from the damage inflicted. Third, boys believe that they
      have control over the amount and frequency of smoking and, thereby, can ensure
      that they will not experience fatal consequences. Boys&rsquo; recurring
      rationalisations build on their view that they are supposed to have fun and will
      not become typical adult smokers. Interventions should address these
      rationalisations in order to increase adolescents&rsquo; perceptions of personal
      vulnerability, and thereby contribute to decreasing adolescent smoking.

PMID- 29659522
TI  - Rice Phyllosphere Bacillus Species and Their Secreted Metabolites Suppress
      Aspergillus flavus Growth and Aflatoxin Production In Vitro and In Maize Seeds.
AB  - The emergence of super-toxigenic strains by recombination is a risk from an
      intensive use of intraspecific aflatoxin (AF) biocontrol agents (BCAs).
      Periodical alternation with interspecific-BCAs will be safer since they preclude
      recombination. We are developing an AF-biocontrol system using rice-associated
      Bacilli reported previously (RABs). More than 50% of RABs inhibited the growth of
      multiple A. flavus strains, with RAB4R being the most inhibitory and RAB1 among
      the least. The fungistatic activity of RAB4R is associated with the lysis of A.
      flavus hyphal tips. In field trails with the top five fungistatic RABs, RAB4R
      consistently inhibited AF contamination of maize by Tox4, a highly toxigenic A.
      flavus strain from Louisiana corn fields. RAB1 did not suppress A. flavus growth,
      but strongly inhibited AF production. Total and HPLC-fractionated lipopeptides
      (LPs) isolated from culture filtrates of RAB1 and RAB4R also inhibited AF
      accumulation. LPs were stable in vitro with little loss of activity even after
      autoclaving, indicating their potential field efficacy as a tank-mix application.
      A. flavus colonization and AF were suppressed in RAB1- or RAB4R-coated maize
      seeds. Since RAB4R provided both fungistatic and strong anti-mycotoxigenic
      activities in the laboratory and field, it can be a potent alternative to
      atoxigenic A. flavus strains. On the other hand, RAB1 may serve as an
      environmentally safe helper BCA with atoxigenic A. flavus strains, due its lack
      of strong fungistatic and hemolytic activities.

PMID- 29659524
TI  - Sensor Technologies for Intelligent Transportation Systems.
AB  - Modern society faces serious problems with transportation systems, including but
      not limited to traffic congestion, safety, and pollution. Information
      communication technologies have gained increasing attention and importance in
      modern transportation systems. Automotive manufacturers are developing in-vehicle
      sensors and their applications in different areas including safety, traffic
      management, and infotainment. Government institutions are implementing roadside
      infrastructures such as cameras and sensors to collect data about environmental
      and traffic conditions. By seamlessly integrating vehicles and sensing devices,
      their sensing and communication capabilities can be leveraged to achieve smart
      and intelligent transportation systems. We discuss how sensor technology can be
      integrated with the transportation infrastructure to achieve a sustainable
      Intelligent Transportation System (ITS) and how safety, traffic control and
      infotainment applications can benefit from multiple sensors deployed in different
      elements of an ITS. Finally, we discuss some of the challenges that need to be
      addressed to enable a fully operational and cooperative ITS environment.

PMID- 29659523
TI  - Antibacterial Efficacy of Silver Nanoparticles on Endometritis Caused by
      Prevotella melaninogenica and Arcanobacterum pyogenes in Dairy Cattle.
AB  - Bovine postpartum diseases remain one of the most significant and highly
      prevalent illnesses with negative effects on the productivity, survival, and
      welfare of dairy cows. Antibiotics are generally considered beneficial in the
      treatment of endometritis; however, frequent usage of each antibiotic drug is
      reason for the emergence of multidrug resistance (MDR) of the pathogenic
      microorganisms, representing a major impediment for the successful diagnosis and
      management of infectious diseases in both humans and animals. We synthesized
      silver nanoparticles (AgNPs) with an average size of 10 nm using the novel
      biomolecule apigenin as a reducing and stabilizing agent, and evaluated the
      efficacy of the AgNPs on the MDR pathogenic bacteria Prevotella melaninogenica
      and Arcanobacterium pyogenes isolated from uterine secretion samples. AgNPs
      inhibited cell viability and biofilm formation in a dose- and time-dependent
      manner. Moreover, the metabolic toxicity of the AgNPs was assessed through
      various cellular assays. The major toxic effect of cell death was caused by an
      increase in oxidative stress, as evidenced by the increased generation of
      reactive oxygen species (ROS), malondialdehyde, protein carbonyl content, and
      nitric oxide. The formation of ROS is considered to be the primary mechanism of
      bacterial death. Therefore, the biomolecule-mediated synthesis of AgNPs shows
      potential as an alternative antimicrobial therapy for bovine metritis and
      endometritis.

PMID- 29659525
TI  - Transcriptomic Analysis of Flower Bud Differentiation in Magnolia sinostellata.
AB  - Magnolias are widely cultivated for their beautiful flowers, but despite their
      popularity, the molecular mechanisms regulating flower bud differentiation have
      not been elucidated. Here, we used paraffin sections and RNA-seq to study the
      process of flower bud differentiation in Magnolia sinostellata. Flower bud
      development occurred between 28 April and 30 May 2017 and was divided into five
      stages: undifferentiated, early flower bud differentiation, petal primordium
      differentiation, stamen primordium differentiation, and pistil primordium
      differentiation. A total of 52,441 expressed genes were identified, of which
      11,592 were significantly differentially expressed in the five bud development
      stages. Of these, 82 genes were involved in the flowering. In addition, MADS-box
      and AP2 family genes play critical roles in the formation of flower organs and 20
      differentially expressed genes associated with flower bud differentiation were
      identified in M. sinostellata. A qRT-PCR analysis verified that the MADS-box and
      AP2 family genes were expressed at high levels during flower bud differentiation.
      Consequently, this study provides a theoretical basis for the genetic regulation
      of flowering in M. sinostellata, which lays a foundation for further research
      into flowering genes and may facilitate the development of new cultivars.

PMID- 29659526
TI  - Improved Seam-Line Searching Algorithm for UAV Image Mosaic with Optical Flow.
AB  - Ghosting and seams are two major challenges in creating unmanned aerial vehicle
      (UAV) image mosaic. In response to these problems, this paper proposes an
      improved method for UAV image seam-line searching. First, an image matching
      algorithm is used to extract and match the features of adjacent images, so that
      they can be transformed into the same coordinate system. Then, the gray scale
      difference, the gradient minimum, and the optical flow value of pixels in
      adjacent image overlapped area in a neighborhood are calculated, which can be
      applied to creating an energy function for seam-line searching. Based on that, an
      improved dynamic programming algorithm is proposed to search the optimal seam
      lines to complete the UAV image mosaic. This algorithm adopts a more adaptive
      energy aggregation and traversal strategy, which can find a more ideal splicing
      path for adjacent UAV images and avoid the ground objects better. The
      experimental results show that the proposed method can effectively solve the
      problems of ghosting and seams in the panoramic UAV images.

PMID- 29659527
TI  - Anti-Diabetic Effects and Anti-Inflammatory Effects of Laminaria japonica and
      Hizikia fusiforme in Skeletal Muscle: In Vitro and In Vivo Model.
AB  - Laminaria japonica (LJ) and Hizikia fusiforme (HF) are brown seaweeds known to
      have various health-promoting effects. In this study, we investigated the anti
      diabetic effects and possible mechanism(s) of LJ and HF by using both in vitro
      and in vivo models. C2C12 myotubes, mouse-derived skeletal muscle cells, treated
      with LF or HF extracts were used for the in vitro model, and muscle tissues from
      C57BL/6N mice fed a high-fat diet supplemented with 5% LF or HF for 16 weeks were
      used for the in vivo model. Although both the LF and HF extracts significantly
      inhibited &alpha;-glucosidase activity in a dose-dependent manner, the HF extract
      had a superior &alpha;-glucosidase inhibition than the LF extract. In addition,
      glucose uptake was significantly increased by LJ- and HF-treated groups when
      compared to the control group. Phosphorylation of protein kinase B and AMP
      activated protein kinase was induced by LJ and HF in both the vivo and in vitro
      skeletal muscle models. Furthermore, LJ and HF significantly decreased tumor
      necrosis factor-&alpha; whereas both extracts increased interleukin (IL)-6 and IL
      10 production in lipopolysaccharide-stimulated C2C12 myotubes. Taken together,
      these findings imply that the brown seaweeds LJ and HF could be useful
      therapeutic agents to attenuate muscle insulin resistance due to diet-induced
      obesity and its associated inflammation.

PMID- 29659528
TI  - Automated Quality Control for Sensor Based Symptom Measurement Performed Outside
      the Lab.
AB  - The use of wearable sensing technology for objective, non-invasive and remote
      clinimetric testing of symptoms has considerable potential. However, the accuracy
      achievable with such technology is highly reliant on separating the useful from
      irrelevant sensor data. Monitoring patient symptoms using digital sensors outside
      of controlled, clinical lab settings creates a variety of practical challenges,
      such as recording unexpected user behaviors. These behaviors often violate the
      assumptions of clinimetric testing protocols, where these protocols are designed
      to probe for specific symptoms. Such violations are frequent outside the lab and
      affect the accuracy of the subsequent data analysis and scientific conclusions.
      To address these problems, we report on a unified algorithmic framework for
      automated sensor data quality control, which can identify those parts of the
      sensor data that are sufficiently reliable for further analysis. Combining both
      parametric and nonparametric signal processing and machine learning techniques,
      we demonstrate that across 100 subjects and 300 clinimetric tests from three
      different types of behavioral clinimetric protocols, the system shows an average
      segmentation accuracy of around 90%. By extracting reliable sensor data, it is
      possible to strip the data of confounding factors in the environment that may
      threaten reproducibility and replicability.

PMID- 29659529
TI  - High-Intensity Intermittent Exercise Increases Fat Oxidation Rate and Reduces
      Postprandial Triglyceride Concentrations.
AB  - (1) Background: This study investigated the effect of acute barehanded whole body
      high-intensity intermittent exercise (HIIE) and moderate intensity and continuous
      exercise (MICE) at the same quantity of energy expenditure on postprandial
      triglyceride (TG) concentrations. (2) Methods: Nine healthy males completed three
      trials (HIIE, MICE and control (CON)) in a random order separated by at least 14
      days. After each intervention, the participants rested for 12 h and consumed a
      high-fat test meal on the next day. The blood samples and respiratory exchange
      ratio were observed in the fasted state and for 4 h after consuming the test
      meal. (3) Results: The HIIE had a significantly higher area under the curve of
      postprandial fat oxidation rate than MICE (p = 0.027) and CON (p = 0.035) and
      exhibited significantly lower postprandial TG concentration than the MICE and CON
      at 2 and 4 h after the test meal. Moreover, the HIIE displayed a higher
      postprandial TG concentration area under the curve than MICE (p = 0.013) and CON
      (p = 0.048). (4) Conclusions: The present study concluded that acute barehanded
      whole body HIIE could significantly lower postprandial TG concentrations. It
      possibly can induce a rise in the postprandial fat oxidation rate.

PMID- 29659530
TI  - Genome Sequence of the Freshwater Yangtze Finless Porpoise.
AB  - The Yangtze finless porpoise (Neophocaena asiaeorientalis ssp. asiaeorientalis)
      is a subspecies of the narrow-ridged finless porpoise (N. asiaeorientalis). In
      total, 714.28 gigabases (Gb) of raw reads were generated by whole-genome
      sequencing of the Yangtze finless porpoise, using an Illumina HiSeq 2000
      platform. After filtering the low-quality and duplicated reads, we assembled a
      draft genome of 2.22 Gb, with contig N50 and scaffold N50 values of 46.69
      kilobases (kb) and 1.71 megabases (Mb), respectively. We identified 887.63 Mb of
      repetitive sequences and predicted 18,479 protein-coding genes in the assembled
      genome. The phylogenetic tree showed a relationship between the Yangtze finless
      porpoise and the Yangtze River dolphin, which diverged approximately 20.84
      million years ago. In comparisons with the genomes of 10 other mammals, we
      detected 44 species-specific gene families, 164 expanded gene families, and 313
      positively selected genes in the Yangtze finless porpoise genome. The assembled
      genome sequence and underlying sequence data are available at the National Center
      for Biotechnology Information under BioProject accession number PRJNA433603.

PMID- 29659531
TI  - Gold Nanoparticles Grafted with PLL-b-PNIPAM: Interplay on Thermal/pH Dual
      Response and Optical Properties.
AB  - Narrowly distributed poly(l-lysine-b-N-isopropylacrylamide) (PLL-b-PNIPAM) was
      prepared through ring-opening polymerization of &epsilon;-benzyloxycarbonyl-l
      lysine N-carboxy-&alpha;-amino anhydride and atom transfer radical polymerization
      of NIPAM, followed with the removal of &epsilon;-benzyloxycarbonyl group. Then
      gold nanoparticles (AuNPs) grafted with PLL-b-PNIPAM (PNIPAM-PLL-AuNPs) were
      obtained by the reduction of chloroauric acid with sodium citrate in the presence
      of PLL-b-PNIPAM. PNIPAM-PLL-AuNPs and its precursors were thoroughly
      characterized by proton magnetic resonance spectroscope, Fourier transform
      infrared spectroscope, UV-vis spectroscope, transmission electron microscopy,
      dynamic light scattering, thermogravimetric analysis, and circular dichroism. The
      obtained PNIPAM-PLL-AuNPs exhibited high colloid stability even at strong
      alkaline (pH = 12) and acidic (pH = 2) conditions. The thermal and pH dual
      responsive behaviors of the grafting PLL-b-PNIPAM chains was observed to be
      affected by AuNPs, while not for the secondary structure of PLL chains.
      Correspondingly, the surface plasmon resonance (SPR) of AuNPs was found to be
      sensitive to both pH value and temperature. A blue shift in the SPR happened both
      with increasing pH value and increasing temperature. The stimuli-response was
      reversible in heating-cooling cycles. The gold nanoparticles with both pH and
      temperature response may have potential applications in biomedical areas and
      biosensors.

PMID- 29659533
TI  - Novel Mutations in pncA Gene of Pyrazinamide Resistant Clinical Isolates of
      Mycobacterium tuberculosis.
AB  - In clinical isolates of Mycobacterium tuberculosis (MTB), resistance to
      pyrazinamide occurs by mutations in any positions of the pncA gene (NC_000962.3)
      especially in nucleotides 359 and 374. In this study we examined the pncA gene
      sequence in clinical isolates of MTB. Genomic DNA of 33 clinical isolates of MTB
      was extracted by the Chelex100 method. The polymerase chain reactions (PCR) were
      performed using specific primers for amplification of 744 bp amplicon comprising
      the coding sequences (CDS) of the pncA gene. PCR products were sequenced by an
      automated sequencing Bioscience system. Additionally, semi Nested-allele specific
      (sNASP) and polymerase chain reaction-restriction fragment length polymorphism
      (PCR-RFLP) methods were carried out for verification of probable mutations in
      nucleotides 359 and 374. Sequencing results showed that from 33 MTB clinical
      isolates, nine pyrazinamide-resistant isolates have mutations. Furthermore, no
      mutation was detected in 24 susceptible strains in the entire 561 bp of the pncA
      gene. Moreover, new mutations of G&rarr;A at position 3 of the pncA gene were
      identified in some of the resistant isolates. Results showed that the sNASP
      method could detect mutations in nucleotide 359 and 374 of the pncA gene, but the
      PCR-RFLP method by the SacII enzyme could not detect these mutations. In
      conclusion, the identification of new mutations in the pncA gene confirmed the
      probable occurrence of mutations in any nucleotides of the pncA gene sequence in
      resistant isolates of MTB.

PMID- 29659532
TI  - Genetic Heterogeneity of SLC22 Family of Transporters in Drug Disposition.
AB  - An important aspect of modern medicine is its orientation to achieve more
      personalized pharmacological treatments. In this context, transporters involved
      in drug disposition have gained well-justified attention. Owing to its broad
      spectrum of substrate specificity, including endogenous compounds and
      xenobiotics, and its strategical expression in organs accounting for drug
      disposition, such as intestine, liver and kidney, the SLC22 family of
      transporters plays an important role in physiology, pharmacology and toxicology.
      Among these carriers are plasma membrane transporters for organic cations (OCTs)
      and anions (OATs) with a marked overlap in substrate specificity. These two major
      clades of SLC22 proteins share a similar membrane topology but differ in their
      degree of genetic variability. Members of the OCT subfamily are highly
      polymorphic, whereas OATs have a lower number of genetic variants. Regarding drug
      disposition, changes in the activity of these variants affect intestinal
      absorption and target tissue uptake, but more frequently they modify plasma
      levels due to enhanced or reduced clearance by the liver and secretion by the
      kidney. The consequences of these changes in transport-associated function
      markedly affect the effectiveness and toxicity of the treatment in patients
      carrying the mutation. In solid tumors, changes in the expression of these
      transporters and the existence of genetic variants substantially determine the
      response to anticancer drugs. Moreover, chemoresistance usually evolves in
      response to pharmacological and radiological treatment. Future personalized
      medicine will require monitoring these changes in a dynamic way to adapt the
      treatment to the weaknesses shown by each tumor at each stage in each patient.

PMID- 29659535
TI  - Adaptive Aggregation Routing to Reduce Delay for Multi-Layer Wireless Sensor
      Networks.
AB  - The quality of service (QoS) regarding delay, lifetime and reliability is the key
      to the application of wireless sensor networks (WSNs). Data aggregation is a
      method to effectively reduce the data transmission volume and improve the
      lifetime of a network. In the previous study, a common strategy required that
      data wait in the queue. When the length of the queue is greater than or equal to
      the predetermined aggregation threshold ( N t ) or the waiting time is equal to
      the aggregation timer ( T t ), data are forwarded at the expense of an increase
      in the delay. The primary contributions of the proposed Adaptive Aggregation
      Routing (AAR) scheme are the following: (a) the senders select the forwarding
      node dynamically according to the length of the data queue, which effectively
      reduces the delay. In the AAR scheme, the senders send data to the nodes with a
      long data queue. The advantages are that first, the nodes with a long data queue
      need a small amount of data to perform aggregation; therefore, the transmitted
      data can be fully utilized to make these nodes aggregate. Second, this scheme
      balances the aggregating and data sending load; thus, the lifetime increases. (b)
      An improved AAR scheme is proposed to improve the QoS. The aggregation deadline (
      T t ) and the aggregation threshold ( N t ) are dynamically changed in the
      network. In WSNs, nodes far from the sink have residual energy because these
      nodes transmit less data than the other nodes. In the improved AAR scheme, the
      nodes far from the sink have a small value of T t and N t to reduce delay, and
      the nodes near the sink are set to a large value of T t and N t to reduce energy
      consumption. Thus, the end to end delay is reduced, a longer lifetime is
      achieved, and the residual energy is fully used. Simulation results demonstrate
      that compared with the previous scheme, the performance of the AAR scheme is
      improved. This scheme reduces the delay by 14.91%, improves the lifetime by
      30.91%, and increases energy efficiency by 76.40%.

PMID- 29659534
TI  - Clinical Management of Low Vitamin D: A Scoping Review of Physicians' Practices.
AB  - The role of vitamin D in the prevention and treatment of non-skeletal health
      issues has received significant media and research attention in recent years.
      Costs associated with clinical management of low vitamin D (LVD) have increased
      exponentially. However, no clear evidence supports vitamin D screening to improve
      health outcomes. Authoritative bodies and professional societies do not recommend
      population-wide vitamin D screening in community-dwelling adults who are
      asymptomatic or at low risk of LVD. To assess patterns of physicians&rsquo;
      management of LVD in this conflicting environment, we conducted a scoping review
      of three electronic databases and the gray literature. Thirty-eight records met
      inclusion criteria and were summarized in an evidence table. Thirteen studies
      published between 2006 and 2015 across seven countries showed a consistent
      increase in vitamin D lab tests and related costs. Many vitamin D testing
      patterns reflected screening rather than targeted testing for individuals at high
      risk of vitamin D deficiency or insufficiency. Interventions aimed at managing
      inappropriate clinical practices related to LVD were effective in the short term.
      Variability and controversy were pervasive in many aspects of vitamin D
      management, shining a light on physicians&rsquo; practices in the face of
      uncertainty. Future research is needed to inform better clinical guidelines and
      to assess implementation practices that encourage evidence-based management of
      LVD in adult populations.

PMID- 29659536
TI  - Glucose Sensor Using U-Shaped Optical Fiber Probe with Gold Nanoparticles and
      Glucose Oxidase.
AB  - In this study, we proposed a U-shaped optical fiber probe fabricated using a
      flame heating method. The probe was packaged in glass tube to reduce human
      factors during experimental testing of the probe as a glucose sensor. The U
      shaped fiber probe was found to have high sensitivity in detecting the very small
      molecule. When the sensor was dipped in solutions with different refractive
      indexes, its wavelength or transmission loss changed. We used electrostatic self
      assembly to bond gold nanoparticles and glucose oxidase (GOD) onto the
      sensor&rsquo;s surface. The results over five cycles of the experiment showed
      that, as the glucose concentration increased, the refractive index of the sensor
      decreased and its spectrum wavelength shifted. The best wavelength sensitivity
      was 2.899 nm/%, and the linearity was 0.9771. The best transmission loss
      sensitivity was 5.101 dB/%, and the linearity was 0.9734. Therefore, the proposed
      U-shaped optical fiber probe with gold nanoparticles and GOD has good potential
      for use as a blood sugar sensor in the future.

PMID- 29659537
TI  - Recent Developments in C-H Activation for Materials Science in the Center for
      Selective C-H Activation.
AB  - Abstract: Organic electronics is a rapidly growing field driven in large part by
      the synthesis of ?-conjugated molecules and polymers. Traditional aryl cross
      coupling reactions such as the Stille and Suzuki have been used extensively in
      the synthesis of ?-conjugated molecules and polymers, but the synthesis of
      intermediates necessary for traditional cross-couplings can include multiple
      steps with toxic and hazardous reagents. Direct arylation through C-H bond
      activation has the potential to reduce the number of steps and hazards while
      being more atom-economical. Within the Center for Selective C-H Functionalization
      (CCHF), we have been developing C-H activation methodology for the synthesis of ?
      conjugated materials of interest, including direct arylation of difficult-to
      functionalize electron acceptor intermediates and living polymerization of ?
      conjugated polymers through C-H activation.

PMID- 29659538
TI  - Cell Adhesion Molecules are Mediated by Photobiomodulation at 660 nm in Diabetic
      Wounded Fibroblast Cells.
AB  - Diabetes affects extracellular matrix (ECM) metabolism, contributing to delayed
      wound healing and lower limb amputation. Application of light
      (photobiomodulation, PBM) has been shown to improve wound healing. This study
      aimed to evaluate the influence of PBM on cell adhesion molecules (CAMs) in
      diabetic wound healing. Isolated human skin fibroblasts were grouped into a
      diabetic wounded model. A diode laser at 660 nm with a fluence of 5 J/cm2 was
      used for irradiation and cells were analysed 48 h post-irradiation. Controls
      consisted of sham-irradiated (0 J/cm2) cells. Real-time reverse transcription
      (RT) quantitative polymerase chain reaction (qPCR) was used to determine the
      expression of CAM-related genes. Ten genes were up-regulated in diabetic wounded
      cells, while 25 genes were down-regulated. Genes were related to transmembrane
      molecules, cell&ndash;cell adhesion, and cell&ndash;matrix adhesion, and also
      included genes related to other CAM molecules. PBM at 660 nm modulated gene
      expression of various CAMs contributing to the increased healing seen in clinical
      practice. There is a need for new therapies to improve diabetic wound healing.
      The application of PBM alongside other clinical therapies may be very beneficial
      in treatment.

PMID- 29659540
TI  - Detection of Ultrasonic Stress Waves in Structures Using 3D Shaped Optic Fiber
      Based on a Mach-Zehnder Interferometer.
AB  - This work proposes a 3D shaped optic fiber sensor for ultrasonic stress waves
      detection based on the principle of a Mach&ndash;Zehnder interferometer. This
      sensor can be used to receive acoustic emission signals in the passive damage
      detection methods and other types of ultrasonic signals propagating in the active
      damage detection methods, such as guided wave-based methods. The sensitivity of
      an ultrasonic fiber sensor based on the Mach&ndash;Zehnder interferometer mainly
      depends on the length of the sensing optical fiber; therefore, the proposed
      sensor achieves the maximum possible sensitivity by wrapping an optical fiber on
      a hollow cylinder with a base. The deformation of the optical fiber is produced
      by the displacement field of guided waves in the hollow cylinder. The sensor was
      first analyzed using the finite element method, which demonstrated its basic
      sensing capacity, and the simulation signals have the same characteristics in the
      frequency domain as the excitation signal. Subsequently, the primary
      investigations were conducted via a series of experiments. The sensor was used to
      detect guided wave signals excited by a piezoelectric wafer in an aluminum plate,
      and subsequently it was tested on a reinforced concrete beam, which produced
      acoustic emission signals via impact loading and crack extension when it was
      loaded to failure. The signals obtained from a piezoelectric acoustic emission
      sensor were used for comparison, and the results indicated that the proposed 3D
      fiber optic sensor can detect ultrasonic signals in the specific frequency
      response range.

PMID- 29659539
TI  - Post-Game High Protein Intake May Improve Recovery of Football-Specific
      Performance during a Congested Game Fixture: Results from the PRO-FOOTBALL Study.
AB  - The effects of protein supplementation on performance recovery and inflammatory
      responses during a simulated one-week in-season microcycle with two games (G1,
      G2) performed three days apart were examined. Twenty football players
      participated in two trials, receiving either milk protein concentrate (1.15 and
      0.26 g/kg on game and training days, respectively) (PRO) or an energy-matched
      placebo (1.37 and 0.31 g/kg of carbohydrate on game and training days,
      respectively) (PLA) according to a randomized, repeated-measures, crossover,
      double-blind design. Each trial included two games and four daily practices.
      Speed, jump height, isokinetic peak torque, and muscle soreness of knee flexors
      (KF) and extensors (KE) were measured before G1 and daily thereafter for six
      days. Blood was drawn before G1 and daily thereafter. Football-specific locomotor
      activity and heart rate were monitored using GPS technology during games and
      practices. The two games resulted in reduced speed (by 3-17%), strength of knee
      flexors (by 12-23%), and jumping performance (by 3-10%) throughout recovery, in
      both trials. Average heart rate and total distance covered during games remained
      unchanged in PRO but not in PLA. Moreover, PRO resulted in a change of smaller
      magnitude in high-intensity running at the end of G2 (75-90 min vs. 0-15 min)
      compared to PLA (P = 0.012). KE concentric strength demonstrated a more prolonged
      decline in PLA (days 1 and 2 after G1, P = 0.014-0.018; days 1, 2 and 3 after G2,
      P = 0.016-0.037) compared to PRO (days 1 after G1, P = 0.013; days 1 and 2 after
      G2, P = 0.014-0.033) following both games. KF eccentric strength decreased
      throughout recovery after G1 (PLA: P=0.001-0.047-PRO: P =0.004-0.22) in both
      trials, whereas after G2 it declined throughout recovery in PLA (P = 0.000-0.013)
      but only during the first two days (P = 0.000-0.014) in PRO. No treatment effect
      was observed for delayed onset of muscle soreness, leukocyte counts, and creatine
      kinase activity. PRO resulted in a faster recovery of protein and lipid
      peroxidation markers after both games. Reduced glutathione demonstrated a more
      short-lived reduction after G2 in PRO compared to PLA. In summary, these results
      provide evidence that protein feeding may more efficiently restore football
      specific performance and strength and provide antioxidant protection during a
      congested game fixture.

PMID- 29659542
TI  - Secure and Usable User-in-a-Context Continuous Authentication in Smartphones
      Leveraging Non-Assisted Sensors.
AB  - Smartphones are equipped with a set of sensors that describe the environment
      (e.g., GPS, noise, etc.) and their current status and usage (e.g., battery
      consumption, accelerometer readings, etc.). Several works have already addressed
      how to leverage such data for user-in-a-context continuous authentication, i.e.,
      determining if the porting user is the authorized one and resides in his regular
      physical environment. This can be useful for an early reaction against robbery or
      impersonation. However, most previous works depend on assisted sensors, i.e.,
      they rely upon immutable elements (e.g., cell towers, satellites, magnetism),
      thus being ineffective in their absence. Moreover, they focus on accuracy
      aspects, neglecting usability ones. For this purpose, in this paper, we explore
      the use of four non-assisted sensors, namely battery, transmitted data, ambient
      light and noise. Our approach leverages data stream mining techniques and offers
      a tunable security-usability trade-off. We assess the accuracy, immediacy,
      usability and readiness of the proposal. Results on 50 users over 24 months show
      that battery readings alone achieve 97.05% of accuracy and 81.35% for audio,
      light and battery all together. Moreover, when usability is at stake, robbery is
      detected in 100 s for the case of battery and in 250 s when audio, light and
      battery are applied. Remarkably, these figures are obtained with moderate
      training and storage needs, thus making the approach suitable for current
      devices.

PMID- 29659543
TI  - Preliminary In-Situ Evaluation of an Innovative, Semi-Flexible Pavement Wearing
      Course Mixture Using Fast Falling Weight Deflectometer.
AB  - In the last forty, years semi-flexible pavements have been successfully employed,
      especially in those areas subjected to heavy and slow-moving loads. They usually
      comprise a wearing course of Grouted Macadam, a composite pavement material that
      provides significant advantages in comparison to both concrete and asphalt
      pavements. On the other hand, the laying process of this material is a two-stage
      operation, and the realization complexity leads to long realization times and
      high initial costs. Therefore, the use of semi-flexible pavements has been
      limited to some fields of application and areas. Recently, an innovative material
      has been developed to be used as an alternative to Grouted Macadam for semi
      flexible pavement wearing course realization. This material should provide
      similar or even superior characteristics compared to traditional Grouted Macadam.
      This will reduce semi-flexible pavement construction time and avoid the need for
      dividing the laying process. This paper presents an experimental program
      involving the use of FastFWD, as an APT device, to evaluate in-situ properties
      and performance of this material. The achieved results regarding the validation
      of this new material by means of FastFWD appear promising both in terms of the
      material's properties and resistance to dynamic load repetitions.

PMID- 29659541
TI  - Zika Virus in the Male Reproductive Tract.
AB  - Arthropod-borne viruses (arboviruses) are resurging across the globe. Zika virus
      (ZIKV) has caused significant concern in recent years because it can lead to
      congenital malformations in babies and Guillain-Barr&eacute; syndrome in adults.
      Unlike other arboviruses, ZIKV can be sexually transmitted and may persist in the
      male reproductive tract. There is limited information regarding the impact of
      ZIKV on male reproductive health and fertility. Understanding the mechanisms that
      underlie persistent ZIKV infections in men is critical to developing effective
      vaccines and therapies. Mouse and macaque models have begun to unravel the
      pathogenesis of ZIKV infection in the male reproductive tract, with the testes
      and prostate gland implicated as potential reservoirs for persistent ZIKV
      infection. Here, we summarize current knowledge regarding the pathogenesis of
      ZIKV in the male reproductive tract, the development of animal models to study
      ZIKV infection at this site, and prospects for vaccines and therapeutics against
      persistent ZIKV infection.

PMID- 29659544
TI  - Health-Related Quality of Life in Patients with Arthritis: A Cross-Sectional
      Survey among Middle-Aged Adults in Chongqing, China.
AB  - : Background: Arthritis is a common disease in China, but few studies have been
      conducted to explore the associated health-related quality of life (HRQoL) and
      its influencing factors in Chongqing, China. This study aimed to explore the
      association of arthritis and HRQoL and probe factors affecting HRQoL among
      arthritis patients. METHODS: A cross-sectional survey was conducted in Chongqing,
      China. A total of 1224 adults were included in the analysis. Medical Outcomes
      Study Short Form 36 Health Survey (SF-36) was used to measure HRQoL. Multiple
      linear regression models (stepwise) and covariance analysis models were used to
      examine the association of arthritis with HRQoL and analyze factors associated
      with HRQoL among arthritis patients. Results: Participants with arthritis had
      poorer HRQoL than those without. Among arthritis patients, the female was
      associated with a poorer state of physical functioning (p < 0.05); unemployed
      patients had a poorer state of role-physical than employed patients (p < 0.05);
      low average monthly income was associated with a poorer state of physical
      functioning (p < 0.01); childhood non-breastfeeding history was associated with a
      poorer state of social functioning (p < 0.01); average or dissatisfied attitude
      to current living conditions was associated with a poorer state of vitality and
      mental health (p < 0.05 for all); moreover, poor or general appetite was
      associated with a poorer state of role-physical, general health, social
      functioning, bodily pain, and role-emotional (p < 0.01 for all). Conclusions:
      Arthritis patients have worse HRQoL than those without in the Chinese population.
      Female, low socioeconomic status, childhood non-breastfeeding history, average or
      dissatisfied attitude to current living conditions and poor or general appetite
      were associated with poorer state of HRQoL among Chinese arthritis patients.

PMID- 29659545
TI  - Identification of Major Rhizobacterial Taxa Affected by a Glyphosate-Tolerant
      Soybean Line via Shotgun Metagenomic Approach.
AB  - The worldwide commercial cultivation of transgenic crops, including glyphosate
      tolerant (GT) soybeans, has increased widely during the past 20 years. However,
      it is accompanied with a growing concern about potential effects of transgenic
      crops on the soil microbial communities, especially on rhizosphere bacterial
      communities. Our previous study found that the GT soybean line NZL06-698 (N698)
      significantly affected rhizosphere bacteria, including some unidentified taxa,
      through 16S rRNA gene (16S rDNA) V4 region amplicon deep sequencing via Illumina
      MiSeq. In this study, we performed 16S rDNA V5-V7 region amplicon deep sequencing
      via Illumina MiSeq and shotgun metagenomic approaches to identify those major
      taxa. Results of these processes revealed that the species richness and evenness
      increased in the rhizosphere bacterial communities of N698, the beta diversity of
      the rhizosphere bacterial communities of N698 was affected, and that certain
      dominant bacterial phyla and genera were related to N698 compared with its
      control cultivar Mengdou12. Consistent with our previous findings, this study
      showed that N698 affects the rhizosphere bacterial communities. In specific, N698
      negatively affects Rahnella, Janthinobacterium, Stenotrophomonas, Sphingomonas
      and Luteibacter while positively affecting Arthrobacter, Bradyrhizobium,
      Ramlibacter and Nitrospira.

PMID- 29659546
TI  - Physical Activity on Prescription with Counsellor Support: A 4-Year Registry
      Based Study in Routine Health Care in Sweden.
AB  - Background: Public health gains from physical activity on prescription (PAP)
      depend on uptake in routine care. We performed an evaluation of the
      implementation, in a Swedish county council, of counsellors who give personalized
      support to PAP recipients aimed at facilitating PAP delivery. The aim was to
      compare characteristics between PAP recipients and the health care population as
      well as between PAP recipients who used and did not use counsellor support. We
      also investigated professional belonging and health care setting of health care
      professionals who prescribed PAP. Methods: All patients&rsquo; &ge;18 years who
      received PAP during 2009&ndash;2012 in primary and secondary care in the County
      Council of Kronoberg were included (n = 4879). Data were retrieved from
      electronic medical records. Main outcome measures were patient and professional
      characteristics. Results: A third of the PAP recipients had diseases in &ge;5
      diagnostic groups and more than half had &ge;11 office visits the year before
      receiving PAP. Counsellor support was used by one-third and PAP recipients who
      used counsellor support had more multiple diagnoses and office visits compared
      with non-users. Physicians issued 44% of prescriptions and primary care was the
      predominant setting. The amount of PAP did not change over time, but the
      proportion of physicians&rsquo; prescriptions decreased while the proportion of
      nurses&rsquo; prescriptions increased. Conclusions: PAP recipients had high
      morbidity and were frequent health care attenders, indicating that PAP was
      predominantly used for secondary or tertiary prevention. PAP rates did not
      increase as intended after the implementation of counsellor support.

PMID- 29659547
TI  - Multi-Sensor Registration in High-Precision CMM Based on a Composite Standard.
AB  - Registration is a critical step in multi-sensor dimensional measurement. As the
      accuracy of registration directly impacts the quality of final results, a
      reference sphere as a common standard is problematic in high-precision
      registration. In this paper, a novel method based on a composite standard is
      proposed to fuse the multiple heterogeneous sensors in high-precision coordinate
      measuring machines (CMMs), which will void the drawbacks of a reference sphere.
      The composite standard consists of a cone and cylinder, which share a same
      central axis. To ensure high precision in the submicron range, or better, the
      standard is manufactured by an ultra-precision machine. Three features of the
      composite standard are inspected by three sensors: a video camera (VC), a tactile
      probe (TP), and a chromatic confocal displacement sensor (CC). All features will
      concentrate on a common point through which the relation between the three
      sensors will be obtained. The errors of each measurement were analyzed
      theoretically, and simulations and real experiments were carried out to verify
      the composite standard. This study demonstrates that the proposed registration
      method is stable and that the standard has potential use for the registration of
      multiple sensors in high-precision dimensional measurement.

PMID- 29659548
TI  - Intelligent Fault Diagnosis of HVCB with Feature Space Optimization-Based Random
      Forest.
AB  - Mechanical faults of high-voltage circuit breakers (HVCBs) always happen over
      long-term operation, so extracting the fault features and identifying the fault
      type have become a key issue for ensuring the security and reliability of power
      supply. Based on wavelet packet decomposition technology and random forest
      algorithm, an effective identification system was developed in this paper. First,
      compared with the incomplete description of Shannon entropy, the wavelet packet
      time-frequency energy rate (WTFER) was adopted as the input vector for the
      classifier model in the feature selection procedure. Then, a random forest
      classifier was used to diagnose the HVCB fault, assess the importance of the
      feature variable and optimize the feature space. Finally, the approach was
      verified based on actual HVCB vibration signals by considering six typical fault
      classes. The comparative experiment results show that the classification accuracy
      of the proposed method with the origin feature space reached 93.33% and reached
      up to 95.56% with optimized input feature vector of classifier. This indicates
      that feature optimization procedure is successful, and the proposed diagnosis
      algorithm has higher efficiency and robustness than traditional methods.

PMID- 29659549
TI  - Blackcurrant Anthocyanins Increase the Levels of Collagen, Elastin, and
      Hyaluronic Acid in Human Skin Fibroblasts and Ovariectomized Rats.
AB  - Blackcurrants (Ribes nigrum L.) contain high levels of anthocyanin polyphenols,
      which have beneficial effects on health, owing to their antioxidant and
      anticarcinogenic properties. Phytoestrogens are plant-derived substances with
      estrogenic activity, which could have beneficial effects on the skin. Estradiol
      secretion decreases during menopause, reducing extracellular matrix (ECM)
      component production by skin fibroblasts. Using a normal human female skin
      fibroblast cell line (TIG113) and ovariectomized rats, the present study
      investigated whether an anthocyanin-rich blackcurrant extract (BCE) and four
      blackcurrant anthocyanins have novel phytoestrogenic activities that could
      benefit the skin in menopausal women. In TIG113 cells, a microarray and the
      Ingenuity(r) Pathway Analysis showed that 1.0 MUg/mL of BCE upregulated the
      expression of many estrogen signaling-related genes. A quantitative RT-PCR
      analysis confirmed that BCE (1.0 or 10.0 MUg/mL) and four types of anthocyanins
      (10 MUM) altered the mRNA expression of ECM proteins and enzymes involved in ECM
      turnover. Immunofluorescence staining indicated that the anthocyanins stimulated
      the expression of ECM proteins, such as collagen (types I and III) and elastin.
      Dietary administration of 3% BCE to ovariectomized rats for 3 months increased
      skin levels of collagen, elastin, and hyaluronic acid. This is the first study to
      show that blackcurrant phytoestrogens have beneficial effects on skin
      experimental models.

PMID- 29659550
TI  - Use of Olive Oil Industrial By-Product for Pasta Enrichment.
AB  - BACKGROUND: During recent years food industries generally produce a large volume
      of wastes both solid and liquid, representing a disposal and potential
      environmental pollution problem. OBJECTIVE: The goal of the study was to
      optimize, from both sensory and nutritional points of view, the formulation of
      durum wheat spaghetti enriched with an olive oil industrial by-product, indicated
      as olive paste. METHODS: Three consecutive steps were carried out. In the first
      one, the olive paste was air-dried at low temperature, milled to record olive
      paste flour and properly analyzed for its biochemical composition. In the second
      step, the olive paste flour was added to the pasta dough at 10% and 15% (w/w). In
      the last step, different concentrations of transglutaminase were added to
      enriched pasta (10% olive paste) to further improve the quality. Sensory
      properties and nutritional content of enriched and control pasta were properly
      measured. RESULTS: Spaghetti with 10% olive paste flour and 0.6% transglutaminase
      were considered acceptable to the sensory panel test. Nutritional analyses showed
      that addition of 10% olive paste flour to pasta considerably increased content of
      flavonoids and total polyphenols. CONCLUSIONS: The proper addition of olive paste
      flour and transglutaminase for pasta enrichment could represent a starting point
      to valorize olive oil industrial by-products and produce new healthy food
      products.

PMID- 29659551
TI  - Time-Course Investigation of Small Molecule Metabolites in MAP-Stored Red Blood
      Cells Using UPLC-QTOF-MS.
AB  - Red blood cells (RBCs) are routinely stored for 35 to 42 days in most countries.
      During storage, RBCs undergo biochemical and biophysical changes known as RBC
      storage lesion, which is influenced by alternative storage additive solutions
      (ASs). Metabolomic studies have been completed on RBCs stored in a number of ASs,
      including SAGM, AS-1, AS-3, AS-5, AS-7, PAGGGM, and MAP. However, the reported
      metabolome analysis of laboratory-made MAP-stored RBCs was mainly focused on the
      time-dependent alterations in glycolytic intermediates during storage. In this
      study, we investigated the time-course of alterations in various small molecule
      metabolites in RBCs stored in commercially used MAP for 49 days using ultra-high
      performance liquid chromatography quadruple time-of-flight mass spectrometry
      (UPLC-QTOF-MS). These alterations indicated that RBC storage lesion is related to
      multiple pathways including glycolysis, pentose phosphate pathway, glutathione
      homeostasis, and purine metabolism. Thus, our findings might be useful for
      understanding the complexity of metabolic mechanisms of RBCs in vitro aging and
      encourage the deployment of systems biology methods to blood products in
      transfusion medicine.

PMID- 29659552
TI  - Improving Pharmacists' Targeting of Patients for Medication Review and
      Deprescription.
AB  - Background: In an acute hospital setting, a multi-disciplinary approach to
      medication review can improve prescribing and medicine selection in patients with
      frailty. There is a need for a clear understanding of the roles and
      responsibilities of pharmacists to ensure that interventions have the greatest
      impact on patient care. Aim: To use a consensus building process to produce
      guidance for pharmacists to support the identification of patients at risk from
      their medicines, and to articulate expected actions and escalation processes.
      Methods: A literature search was conducted and evidence used to establish a set
      of ten scenarios often encountered in hospitalised patients, with six or more
      possible actions. Four consultant physicians and four senior pharmacists ranked
      their levels of agreement with the listed actions. The process was redrafted and
      repeated until consensus was reached and interventions were defined. Outcome:
      Generalised guidance for reviewing older adults' medicines was developed,
      alongside escalation processes that should be followed in a specific set of
      clinical situations. The panel agreed that both pharmacists and physicians have
      an active role to play in medication review, and face-to-face communication is
      always preferable to facilitate informed decision making. Only prescribers should
      deprescribe, however pharmacists who are not also trained as prescribers may
      temporarily "hold" medications in the best interests of the patient with
      appropriate documentation and a follow up discussion with the prescribing team.
      The consensus was that a combination of age, problematic polypharmacy, and the
      presence of medication-related problems, were the most important factors in the
      identification of patients who would benefit most from a comprehensive medication
      review. Conclusions: Guidance on the identification of patients on inappropriate
      medicines, and subsequent pharmacist-led intervention to prompt and promote
      deprescribing, has been developed for implementation in an acute hospital.

PMID- 29659555
TI  - The CiCs(SiI)n Defect in Silicon from a Density Functional Theory Perspective.
AB  - Carbon constitutes a significant defect in silicon (Si) as it can interact with
      intrinsic point defects and affect the operation of devices. In heavily
      irradiated Si containing carbon the initially produced carbon interstitial-carbon
      substitutional (CiCs) defect can associate with self-interstitials (SiI's) to
      form, in the course of irradiation, the CiCs(SiI) defect and further form larger
      complexes namely, CiCs(SiI)n defects, by the sequential trapping of self
      interstitials defects. In the present study, we use density functional theory to
      clarify the structure and energetics of the CiCs(SiI)n defects. We report that
      the lowest energy CiCs(SiI) and CiCs(SiI)2 defects are strongly bound with -2.77
      and -5.30 eV, respectively.

PMID- 29659553
TI  - Therapeutic Potential of Annexin A1 in Ischemia Reperfusion Injury.
AB  - Cardiovascular disease (CVD) continues to be the leading cause of death in the
      world. Increased inflammation and an enhanced thrombotic milieu represent two
      major complications of CVD, which can culminate into an ischemic event. Treatment
      for these life-threatening complications remains reperfusion and restoration of
      blood flow. However, reperfusion strategies may result in ischemia-reperfusion
      injury (I/RI) secondary to various cardiovascular pathologies, including
      myocardial infarction and stroke, by furthering the inflammatory and thrombotic
      responses and delivering inflammatory mediators to the affected tissue. Annexin
      A1 (AnxA1) and its mimetic peptides are endogenous anti-inflammatory and pro
      resolving mediators, known to have significant effects in resolving inflammation
      in a variety of disease models. Mounting evidence suggests that AnxA1, which
      interacts with the formyl peptide receptor (FPR) family, may have a significant
      role in mitigating I/RI associated complications. In this review article, we
      focus on how AnxA1 plays a protective role in the I/R based vascular pathologies.

PMID- 29659556
TI  - Electrochemical Determination of Norepinephrine by Means of Modified Glassy
      Carbon Electrodes with Carbon Nanotubes and Magnetic Nanoparticles of Cobalt
      Ferrite.
AB  - This study describes the electrochemical preparation of the electrocatalytic
      oxidation/reduction of noradrenaline in modified glassy carbon of cobalt ferrite
      nanoparticles and carbon nanotubes (GC/MWCNT/FCo98). The cobalt ferrite powder
      was characterized by X-ray diffraction (XRD) and transmission electron microscopy
      (TEM). The optimum conditions found in an electrode composition were 4 MUL of
      cobalt ferrite and 10 MUL of carbon nanotubes in 0.1 mol L-1 PBS at pH 7.0. The
      electrode displays electrochemical behavior in a wide potential range (-0.4 to
      1.0 V vs. Ag/AgCl), high conductivity, and electrode stability/durability in 0.1
      mol L-1 PBS. Catalytic oxidation of noradrenaline was performed at the unmodified
      GC electrode at +0.60 V vs. Ag/AgCl and current of 0.17 MUA and modified GC with
      cobalt ferrite nanoparticles and carbon nanotubes at +0.54 V vs. Ag/AgCl and
      current of 0.23 mA. With regard to the anodic peak current (Ipa) versus
      noradrenaline concentration by means of the amperometric method at the modified
      electrode, (which is linear in the 0.16 and 1.91 mmol L-1 concentration range),
      the concentration limit was 0.76 MUmol L-1. In this way, the modified electrode
      GC/MWCNT/FCo98 was found to be a promising application for the determination of
      this neurotransmitter in the area of neuroscience.

PMID- 29659557
TI  - Development of a 2 MHz Sonar Sensor for Inspection of Bridge Substructures.
AB  - Hydraulic factors account for a large part of the causes of bridge collapse. Due
      to the nature of the underwater environment, quick and accurate inspection is
      required when damage occurs. In this study, we developed a 2 MHz side scan sonar
      sensor module and effective operation technique by improving the limitations of
      existing sonar. Through field tests, we analyzed the correlation of factors
      affecting the resolution of the sonar data such as the angle of survey, the
      distance from the underwater structure and the water depth. The effect of the
      distance and the water depth and the structure on the survey angle was 66~82%. We
      also derived the relationship between these factors as a regression model for
      effective operating techniques. It is considered that application of the
      developed 2 MHz side scan sonar and its operation method could contribute to
      prevention of bridge collapses and disasters by quickly and accurately checking
      the damage of bridge substructures due to hydraulic factors.

PMID- 29659554
TI  - Demyelination in Multiple Sclerosis: Reprogramming Energy Metabolism and
      Potential PPARgamma Agonist Treatment Approaches.
AB  - Demyelination in multiple sclerosis (MS) cells is the site of several energy
      metabolic abnormalities driven by dysregulation between the opposed interplay of
      peroxisome proliferator-activated receptor gamma (PPARgamma) and WNT/beta-catenin
      pathways. We focus our review on the opposing interactions observed in
      demyelinating processes in MS between the canonical WNT/beta-catenin pathway and
      PPARgamma and their reprogramming energy metabolism implications. Demyelination
      in MS is associated with chronic inflammation, which is itself associated with
      the release of cytokines by CD4+ Th17 cells, and downregulation of PPARgamma
      expression leading to the upregulation of the WNT/beta-catenin pathway.
      Upregulation of WNT/beta-catenin signaling induces activation of glycolytic
      enzymes that modify their energy metabolic behavior. Then, in MS cells, a large
      portion of cytosolic pyruvate is converted into lactate. This phenomenon is
      called the Warburg effect, despite the availability of oxygen. The Warburg effect
      is the shift of an energy transfer production from mitochondrial oxidative
      phosphorylation to aerobic glycolysis. Lactate production is correlated with
      increased WNT/beta-catenin signaling and demyelinating processes by inducing
      dysfunction of CD4+ T cells leading to axonal and neuronal damage. In MS,
      downregulation of PPARgamma decreases insulin sensitivity and increases
      neuroinflammation. PPARgamma agonists inhibit Th17 differentiation in CD4+ T
      cells and then diminish release of cytokines. In MS, abnormalities in the
      regulation of circadian rhythms stimulate the WNT pathway to initiate the
      demyelination process. Moreover, PPARgamma contributes to the regulation of some
      key circadian genes. Thus, PPARgamma agonists interfere with reprogramming energy
      metabolism by directly inhibiting the WNT/beta-catenin pathway and circadian
      rhythms and could appear as promising treatments in MS due to these interactions.

PMID- 29659558
TI  - Special Issue Introduction: Inherited Retinal Disease: Novel Candidate Genes,
      Genotype-Phenotype Correlations, and Inheritance Models.
AB  - Inherited retinal diseases (IRDs) are genetically and clinically heterogeneous
      disorders.[...].

PMID- 29659559
TI  - Vitamin D and the Liver-Correlation or Cause?
AB  - Vitamin D is becoming increasingly accepted as an important physiological
      regulator outside of its classical role in skeletal homeostasis. A growing body
      of evidence connects vitamin D with hepatic disease. This review summarises the
      role of vitamin D in liver homeostasis and disease and discusses the therapeutic
      potential of vitamin D-based treatments to protect against hepatic disease
      progression and to improve response to treatment. While pre-clinical experimental
      data is promising, clinical trials around liver diseases have mostly been under
      powered, and further studies will be required to clarify whether vitamin D or
      vitamin D analogues have beneficial effects on liver disease.

PMID- 29659560
TI  - Androgen Receptor Is Inactivated and Degraded in Bladder Cancer Cells by Phenyl
      Glucosamine via miR-449a Restoration.
AB  - BACKGROUND Bladder cancer caused by exposure to aniline dyes, chronic cystitis,
      and smoking is detected in approximately 70 000 new cases annually. In the USA
      alone, it leads to 15 000 deaths every year. In the present study, we
      investigated the role of 3-((4'-amino-[1,1'-biphenyl]-4-yl)amino)-4-bromo-5-oxo
      2,5-dihydrofuran-2-yl acetate (ABDHFA) in the inhibition of bladder cancer cell
      viability. MATERIAL AND METHODS Viability of cells was examined using MTT assay
      and distribution of cell cycle was assessed by flow cytometry. Expression of
      cyclin D1, androgen, prostate-specific antigen (PSA), and miR-449a was analyzed
      using Western blot and quantitative real-time polymerase chain reaction assays.
      RESULTS The results demonstrated that ABDHFA treatment inhibited viability of
      UMUC3 and TCCSUP AR-positive bladder cancer cells. ABDHFA treatment led to break
      down of AR in UMUC3 and TCCSUP cells after 48 h in a dose-dependent manner. Up
      regulation of miR-449a by lentivirus transfection down-regulated the AR
      signalling pathway. In UMUC3 and TCCSUP cells, ABDHFA treatment led to inhibition
      of mRNA and protein expression corresponding to AR. CONCLUSIONS In summary, the
      present study demonstrates that proliferation of AR-positive bladder carcinoma
      cells is markedly reduced by ABDHFA treatment through arrest of cell cycle and
      degradation of AR protein. Thus, ABDHFA, a novel compound, can be used for the
      treatment of bladder cancer.

PMID- 29659561
TI  - Origins of scale invariance in vocalization sequences and speech.
AB  - To communicate effectively animals need to detect temporal vocalization cues that
      vary over several orders of magnitude in their amplitude and frequency content.
      This large range of temporal cues is evident in the power-law scale-invariant
      relationship between the power of temporal fluctuations in sounds and the sound
      modulation frequency (f). Though various forms of scale invariance have been
      described for natural sounds, the origins and implications of scale invariant
      phenomenon remain unknown. Using animal vocalization sequences, including
      continuous human speech, and a stochastic model of temporal amplitude
      fluctuations we demonstrate that temporal acoustic edges are the primary acoustic
      cue accounting for the scale invariant phenomenon. The modulation spectrum of
      vocalization sequences and the model both exhibit a dual regime lowpass structure
      with a flat region at low modulation frequencies and scale invariant 1/f2 trend
      for high modulation frequencies. Moreover, we find a time-frequency tradeoff
      between the average vocalization duration of each vocalization sequence and the
      cutoff frequency beyond which scale invariant behavior is observed. These results
      indicate that temporal edges are universal features responsible for scale
      invariance in vocalized sounds. This is significant since temporal acoustic edges
      are salient perceptually and the auditory system could exploit such statistical
      regularities to minimize redundancies and generate compact neural representations
      of vocalized sounds.

PMID- 29659562
TI  - Organic cation transporter 1 (OCT1) modulates multiple cardiometabolic traits
      through effects on hepatic thiamine content.
AB  - A constellation of metabolic disorders, including obesity, dysregulated lipids,
      and elevations in blood glucose levels, has been associated with cardiovascular
      disease and diabetes. Analysis of data from recently published genome-wide
      association studies (GWAS) demonstrated that reduced-function polymorphisms in
      the organic cation transporter, OCT1 (SLC22A1), are significantly associated with
      higher total cholesterol, low-density lipoprotein (LDL) cholesterol, and
      triglyceride (TG) levels and an increased risk for type 2 diabetes mellitus, yet
      the mechanism linking OCT1 to these metabolic traits remains puzzling. Here, we
      show that OCT1, widely characterized as a drug transporter, plays a key role in
      modulating hepatic glucose and lipid metabolism, potentially by mediating
      thiamine (vitamin B1) uptake and hence its levels in the liver. Deletion of Oct1
      in mice resulted in reduced activity of thiamine-dependent enzymes, including
      pyruvate dehydrogenase (PDH), which disrupted the hepatic glucose-fatty acid
      cycle and shifted the source of energy production from glucose to fatty acids,
      leading to a reduction in glucose utilization, increased gluconeogenesis, and
      altered lipid metabolism. In turn, these effects resulted in increased total body
      adiposity and systemic levels of glucose and lipids. Importantly, wild-type mice
      on thiamine deficient diets (TDs) exhibited impaired glucose metabolism that
      phenocopied Oct1 deficient mice. Collectively, our study reveals a critical role
      of hepatic thiamine deficiency through OCT1 deficiency in promoting the metabolic
      inflexibility that leads to the pathogenesis of cardiometabolic disease.

PMID- 29659563
TI  - Backbone Brackets and Arginine Tweezers delineate Class I and Class II aminoacyl
      tRNA synthetases.
AB  - The origin of the machinery that realizes protein biosynthesis in all organisms
      is still unclear. One key component of this machinery are aminoacyl tRNA
      synthetases (aaRS), which ligate tRNAs to amino acids while consuming ATP.
      Sequence analyses revealed that these enzymes can be divided into two
      complementary classes. Both classes differ significantly on a sequence and
      structural level, feature different reaction mechanisms, and occur in diverse
      oligomerization states. The one unifying aspect of both classes is their function
      of binding ATP. We identified Backbone Brackets and Arginine Tweezers as most
      compact ATP binding motifs characteristic for each Class. Geometric analysis
      shows a structural rearrangement of the Backbone Brackets upon ATP binding,
      indicating a general mechanism of all Class I structures. Regarding the origin of
      aaRS, the Rodin-Ohno hypothesis states that the peculiar nature of the two aaRS
      classes is the result of their primordial forms, called Protozymes, being encoded
      on opposite strands of the same gene. Backbone Brackets and Arginine Tweezers
      were traced back to the proposed Protozymes and their more efficient successors,
      the Urzymes. Both structural motifs can be observed as pairs of residues in
      contemporary structures and it seems that the time of their addition, indicated
      by their placement in the ancient aaRS, coincides with the evolutionary trace of
      Proto- and Urzymes.

PMID- 29659564
TI  - Multiscale modelization in a small virus: Mechanism of proton channeling and its
      role in triggering capsid disassembly.
AB  - In this work, we assess a previously advanced hypothesis that predicts the
      existence of ion channels in the capsid of small and non-enveloped icosahedral
      viruses. With this purpose we examine Triatoma Virus (TrV) as a case study. This
      virus has a stable capsid under highly acidic conditions but disassembles and
      releases the genome in alkaline environments. Our calculations range from a
      subtle sub-atomic proton interchange to the dismantling of a large-scale system
      representing several million of atoms. Our results provide structure-based
      explanations for the three roles played by the capsid to enable genome release.
      First, we observe, for the first time, the formation of a hydrophobic gate in the
      cavity along the five-fold axis of the wild-type virus capsid, which can be
      disrupted by an ion located in the pore. Second, the channel enables protons to
      permeate the capsid through a unidirectional Grotthuss-like mechanism, which is
      the most likely process through which the capsid senses pH. Finally, assuming
      that the proton leak promotes a charge imbalance in the interior of the capsid,
      we model an internal pressure that forces shell cracking using coarse-grained
      simulations. Although qualitatively, this last step could represent the mechanism
      of capsid opening that allows RNA release. All of our calculations are in
      agreement with current experimental data obtained using TrV and describe a
      cascade of events that could explain the destabilization and disassembly of
      similar icosahedral viruses.

PMID- 29659565
TI  - Cyclic di-AMP regulation of osmotic homeostasis is essential in Group B
      Streptococcus.
AB  - Cyclic nucleotides are universally used as secondary messengers to control
      cellular physiology. Among these signalling molecules, cyclic di-adenosine
      monophosphate (c-di-AMP) is a specific bacterial second messenger recognized by
      host cells during infections and its synthesis is assumed to be necessary for
      bacterial growth by controlling a conserved and essential cellular function. In
      this study, we sought to identify the main c-di-AMP dependent pathway in
      Streptococcus agalactiae, the etiological agent of neonatal septicaemia and
      meningitis. By conditionally inactivating dacA, the only diadenyate cyclase gene,
      we confirm that c-di-AMP synthesis is essential in standard growth conditions.
      However, c-di-AMP synthesis becomes rapidly dispensable due to the accumulation
      of compensatory mutations. We identified several mutations restoring the
      viability of a DeltadacA mutant, in particular a loss-of-function mutation in the
      osmoprotectant transporter BusAB. Identification of c-di-AMP binding proteins
      revealed a conserved set of potassium and osmolyte transporters, as well as the
      BusR transcriptional factor. We showed that BusR negatively regulates busAB
      transcription by direct binding to the busAB promoter. Loss of BusR repression
      leads to a toxic busAB expression in absence of c-di-AMP if osmoprotectants, such
      as glycine betaine, are present in the medium. In contrast, deletion of the gdpP
      c-di-AMP phosphodiesterase leads to hyperosmotic susceptibility, a phenotype
      dependent on a functional BusR. Taken together, we demonstrate that c-di-AMP is
      essential for osmotic homeostasis and that the predominant mechanism is dependent
      on the c-di-AMP binding transcriptional factor BusR. The regulation of osmotic
      homeostasis is likely the conserved and essential function of c-di-AMP, but each
      species has evolved specific c-di-AMP mechanisms of osmoregulation to adapt to
      its environment.

PMID- 29659566
TI  - Biocuration: Distilling data into knowledge.
AB  - Data, including information generated from them by processing and analysis, are
      an asset with measurable value. The assets that biological research funding
      produces are the data generated, the information derived from these data, and,
      ultimately, the discoveries and knowledge these lead to. From the time when Henry
      Oldenburg published the first scientific journal in 1665 (Proceedings of the
      Royal Society) to the founding of the United States National Library of Medicine
      in 1879 to the present, there has been a sustained drive to improve how
      researchers can record and discover what is known. Researchers' experimental work
      builds upon years and (collectively) billions of dollars' worth of earlier work.
      Today, researchers are generating data at ever-faster rates because of advances
      in instrumentation and technology, coupled with decreases in production costs.
      Unfortunately, the ability of researchers to manage and disseminate their results
      has not kept pace, so their work cannot achieve its maximal impact. Strides have
      recently been made, but more awareness is needed of the essential role that
      biological data resources, including biocuration, play in maintaining and linking
      this ever-growing flood of data and information. The aim of this paper is to
      describe the nature of data as an asset, the role biocurators play in increasing
      its value, and consistent, practical means to measure effectiveness that can
      guide planning and justify costs in biological research information resources'
      development and management.

PMID- 29659567
TI  - Cytokinin stabilizes WUSCHEL by acting on the protein domains required for
      nuclear enrichment and transcription.
AB  - Concentration-dependent transcriptional regulation and the spatial regulation of
      transcription factor levels are poorly studied in plant development. WUSCHEL, a
      stem cell-promoting homeodomain transcription factor, accumulates at a higher
      level in the rib meristem than in the overlying central zone, which harbors stem
      cells in the shoot apical meristems of Arabidopsis thaliana. The differential
      accumulation of WUSCHEL in adjacent cells is critical for the spatial regulation
      and levels of CLAVATA3, a negative regulator of WUSCHEL transcription. Earlier
      studies have revealed that DNA-dependent dimerization, subcellular partitioning
      and protein destabilization control WUSCHEL protein levels and spatial
      accumulation. Moreover, the destabilization of WUSCHEL may also depend on the
      protein concentration. However, the roles of extrinsic spatial cues in
      maintaining differential accumulation of WUS are not understood. Through
      transient manipulation of hormone levels, hormone response patterns and analysis
      of the receptor mutants, we show that cytokinin signaling in the rib meristem
      acts through the transcriptional regulatory domains, the acidic domain and the
      WUSCHEL-box, to stabilize the WUS protein. Furthermore, we show that the same
      WUSCHEL-box functions as a degron sequence in cytokinin deficient regions in the
      central zone, leading to the destabilization of WUSCHEL. The coupled functions of
      the WUSCHEL-box in nuclear retention as described earlier, together with
      cytokinin sensing, reinforce higher nuclear accumulation of WUSCHEL in the rib
      meristem. In contrast a sub-threshold level may expose the WUSCHEL-box to
      destabilizing signals in the central zone. Thus, the cytokinin signaling acts as
      an asymmetric spatial cue in stabilizing the WUSCHEL protein to lead to its
      differential accumulation in neighboring cells, which is critical for
      concentration-dependent spatial regulation of CLAVATA3 transcription and meristem
      maintenance. Furthermore, our work shows that cytokinin response is regulated
      independently of the WUSCHEL function which may provide robustness to the
      regulation of WUSCHEL concentration.

PMID- 29659568
TI  - Introduced bullfrog facilitates pathogen invasion in the western United States.
AB  - Batrachochytrium dendrobatidis (Bd), a causal agent of the amphibian fungal skin
      disease chytridiomycosis, has been implicated in the decline and extinction of
      over 200 species worldwide since the 1970s. Despite almost two decades of
      research, the history of Bd and its global spread is not well understood.
      However, the spread of the Global Panzootic Lineage of Bd (Bd-GPL), the lineage
      associated with amphibian die-offs, has been linked with the American bullfrog
      (Rana [Aqurana] catesbeiana) and global trade. Interestingly, R. catesbeiana is
      native to the eastern U.S., where no Bd-related declines have been observed
      despite Bd's presence since the late 1800s. In contrast Bd has been found to have
      emerged in California and Mexico in the 1960s and 1970s, after which epizootics
      (i.e., epidemics in wildlife) ensued. We hypothesize that Bd-GPL spread from the
      eastern U.S. with the introduction of R. catesbeiana into the western US,
      resulting in epizootics and declines of native host species. Using museum
      records, we investigated the historical relationship between R. catesbeiana and
      Bd invasion in the western US and found that R. catesbeiana arrived in the same
      year or prior to Bd in most western watersheds that had data for both species,
      suggesting that Bd-GPL may have originated in the eastern US and R. catesbeiana
      may have facilitated Bd invasion in the western US. To predict areas with
      greatest suitability for Bd, we created a suitability model by integrating
      habitat suitability and host availability. When we incorporated invasion history
      with high Bd suitability, we found that watersheds with non-native R. catesbeiana
      in the mountain ranges of the West Coast have the highest disease risk. These
      findings shed light on the invasion history and disease dynamics of Bd in North
      America. Targeted historical surveys using archived specimens in natural history
      collections and present-day field surveys along with more localized, community
      level studies, monitoring, and surveillance are needed to further test this
      hypothesis and grow our understanding of the disease ecology and host-pathogen
      dynamics of Bd.

PMID- 29659569
TI  - Targeted next generation sequencing identifies functionally deleterious germline
      mutations in novel genes in early-onset/familial prostate cancer.
AB  - Considering that mutations in known prostate cancer (PrCa) predisposition genes,
      including those responsible for hereditary breast/ovarian cancer and Lynch
      syndromes, explain less than 5% of early-onset/familial PrCa, we have sequenced
      94 genes associated with cancer predisposition using next generation sequencing
      (NGS) in a series of 121 PrCa patients. We found monoallelic
      truncating/functionally deleterious mutations in seven genes, including ATM and
      CHEK2, which have previously been associated with PrCa predisposition, and five
      new candidate PrCa associated genes involved in cancer predisposing recessive
      disorders, namely RAD51C, FANCD2, FANCI, CEP57 and RECQL4. Furthermore, using in
      silico pathogenicity prediction of missense variants among 18 genes associated
      with breast/ovarian cancer and/or Lynch syndrome, followed by KASP genotyping in
      710 healthy controls, we identified "likely pathogenic" missense variants in ATM,
      BRIP1, CHEK2 and TP53. In conclusion, this study has identified putative PrCa
      predisposing germline mutations in 14.9% of early-onset/familial PrCa patients.
      Further data will be necessary to confirm the genetic heterogeneity of inherited
      PrCa predisposition hinted in this study.

PMID- 29659570
TI  - Laboratory mouse housing conditions can be improved using common environmental
      enrichment without compromising data.
AB  - Animal welfare requires the adequate housing of animals to ensure health and well
      being. The application of environmental enrichment is a way to improve the well
      being of laboratory animals. However, it is important to know whether these
      enrichment items can be incorporated in experimental mouse husbandry without
      creating a divide between past and future experimental results. Previous small
      scale studies have been inconsistent throughout the literature, and it is not yet
      completely understood whether and how enrichment might endanger comparability of
      results of scientific experiments. Here, we measured the effect on means and
      variability of 164 physiological parameters in 3 conditions: with nesting
      material with or without a shelter, comparing these 2 conditions to a "barren"
      regime without any enrichments. We studied a total of 360 mice from each of 2
      mouse strains (C57BL/6NTac and DBA/2NCrl) and both sexes for each of the 3
      conditions. Our study indicates that enrichment affects the mean values of some
      of the 164 parameters with no consistent effects on variability. However, the
      influence of enrichment appears negligible compared to the effects of other
      influencing factors. Therefore, nesting material and shelters may be used to
      improve animal welfare without impairment of experimental outcome or loss of
      comparability to previous data collected under barren housing conditions.

PMID- 29659571
TI  - Allostery in the dengue virus NS3 helicase: Insights into the NTPase cycle from
      molecular simulations.
AB  - The C-terminus domain of non-structural 3 (NS3) protein of the Flaviviridae
      viruses (e.g. HCV, dengue, West Nile, Zika) is a nucleotide triphosphatase
      (NTPase) -dependent superfamily 2 (SF2) helicase that unwinds double-stranded RNA
      while translocating along the nucleic polymer. Due to these functions, NS3 is an
      important target for antiviral development yet the biophysics of this enzyme are
      poorly understood. Microsecond-long molecular dynamic simulations of the dengue
      NS3 helicase domain are reported from which allosteric effects of RNA and NTPase
      substrates are observed. The presence of a bound single-stranded RNA
      catalytically enhances the phosphate hydrolysis reaction by affecting the
      dynamics and positioning of waters within the hydrolysis active site. Coupled
      with results from the simulations, electronic structure calculations of the
      reaction are used to quantify this enhancement to be a 150-fold increase, in
      qualitative agreement with the experimental enhancement factor of 10-100.
      Additionally, protein-RNA interactions exhibit NTPase substrate-induced
      allostery, where the presence of a nucleotide (e.g. ATP or ADP) structurally
      perturbs residues in direct contact with the phosphodiester backbone of the RNA.
      Residue-residue network analyses highlight pathways of short ranged interactions
      that connect the two active sites. These analyses identify motif V as a highly
      connected region of protein structure through which energy released from either
      active site is hypothesized to move, thereby inducing the observed allosteric
      effects. These results lay the foundation for the design of novel allosteric
      inhibitors of NS3.

PMID- 29659572
TI  - A computational study of astrocytic glutamate influence on post-synaptic neuronal
      excitability.
AB  - The ability of astrocytes to rapidly clear synaptic glutamate and purposefully
      release the excitatory transmitter is critical in the functioning of synapses and
      neuronal circuits. Dysfunctions of these homeostatic functions have been
      implicated in the pathology of brain disorders such as mesial temporal lobe
      epilepsy. However, the reasons for these dysfunctions are not clear from
      experimental data and computational models have been developed to provide further
      understanding of the implications of glutamate clearance from the extracellular
      space, as a result of EAAT2 downregulation: although they only partially account
      for the glutamate clearance process. In this work, we develop an explicit model
      of the astrocytic glutamate transporters, providing a more complete description
      of the glutamate chemical potential across the astrocytic membrane and its
      contribution to glutamate transporter driving force based on thermodynamic
      principles and experimental data. Analysis of our model demonstrates that
      increased astrocytic glutamate content due to glutamine synthetase downregulation
      also results in increased postsynaptic quantal size due to gliotransmission.
      Moreover, the proposed model demonstrates that increased astrocytic glutamate
      could prolong the time course of glutamate in the synaptic cleft and enhances
      astrocyte-induced slow inward currents, causing a disruption to the clarity of
      synaptic signalling and the occurrence of intervals of higher frequency
      postsynaptic firing. Overall, our work distilled the necessity of a low
      astrocytic glutamate concentration for reliable synaptic transmission of
      information and the possible implications of enhanced glutamate levels as in
      epilepsy.

PMID- 29659573
TI  - Whole-body iron transport and metabolism: Mechanistic, multi-scale model to
      improve treatment of anemia in chronic kidney disease.
AB  - Iron plays vital roles in the human body including enzymatic processes, oxygen
      transport via hemoglobin and immune response. Iron metabolism is characterized by
      ~95% recycling and minor replenishment through diet. Anemia of chronic kidney
      disease (CKD) is characterized by a lack of synthesis of erythropoietin leading
      to reduced red blood cell (RBC) formation and aberrant iron recycling. Treatment
      of CKD anemia aims to normalize RBC count and serum hemoglobin. Clinically, the
      various fluxes of iron transport and accumulation are not measured so that
      changes during disease (e.g., CKD) and treatment are unknown. Unwanted iron
      accumulation in patients is known to lead to adverse effects. Current whole-body
      models lack the mechanistic details of iron transport related to RBC maturation,
      transferrin (Tf and TfR) dynamics and assume passive iron efflux from
      macrophages. Hence, they are not predictive of whole-body iron dynamics and
      cannot be used to design individualized patient treatment. For prediction, we
      developed a mechanistic, multi-scale computational model of whole-body iron
      metabolism incorporating four compartments containing major pools of iron and RBC
      generation process. The model accounts for multiple forms of iron in vivo,
      mechanisms involved in iron uptake and release and their regulation. Furthermore,
      the model is interfaced with drug pharmacokinetics to allow simulation of
      treatment dynamics. We calibrated our model with experimental and clinical data
      from peer-reviewed literature to reliably simulate CKD anemia and the effects of
      current treatment involving combination of epoietin-alpha and iron dextran. This
      in silico whole-body model of iron metabolism predicts that a year of treatment
      can potentially lead to 90% downregulation of ferroportin (FPN) levels, 15-fold
      increase in iron stores with only a 20% increase in iron flux from the reticulo
      endothelial system (RES). Model simulations quantified unmeasured iron fluxes,
      previously unknown effects of treatment on FPN-level and iron stores in the RES.
      This mechanistic whole-body model can be the basis for future studies that
      incorporate iron metabolism together with related clinical experiments. Such an
      approach could pave the way for development of effective personalized treatment
      of CKD anemia.

PMID- 29659574
TI  - The impact of school water, sanitation, and hygiene improvements on infectious
      disease using serum antibody detection.
AB  - BACKGROUND: Evidence from recent studies assessing the impact of school water,
      sanitation and hygiene (WASH) interventions on child health has been mixed. Self
      reports of disease are subject to bias, and few WASH impact evaluations employ
      objective health measures to assess reductions in disease and exposure to
      pathogens. We utilized antibody responses from dried blood spots (DBS) to measure
      the impact of a school WASH intervention on infectious disease among pupils in
      Mali. METHODOLOGY/PRINCIPAL FINDINGS: We randomly selected 21 beneficiary primary
      schools and their 21 matched comparison schools participating in a matched
      control trial of a comprehensive school-based WASH intervention in Mali. DBS were
      collected from 20 randomly selected pupils in each school (n = 807). We analyzed
      eluted IgG from the DBS using a Luminex multiplex bead assay to 28 antigens from
      17 different pathogens. Factor analysis identified three distinct latent
      variables representing vector-transmitted disease (driven primarily by dengue),
      food/water-transmitted enteric disease (driven primarily by Escherichia coli and
      Vibrio cholerae), and person-to-person transmitted enteric disease (driven
      primarily by norovirus). Data were analyzed using a linear latent variable model.
      Antibody evidence of food/water-transmitted enteric disease (change in latent
      variable mean (beta) = -0.24; 95% CI: -0.53, -0.13) and person-to-person
      transmitted enteric disease (beta = -0.17; 95% CI: -0.42, -0.04) was lower among
      pupils attending beneficiary schools. There was no difference in antibody
      evidence of vector-transmitted disease (beta = 0.11; 95% CI: -0.05, 0.33).
      CONCLUSIONS/SIGNIFICANCE: Evidence of enteric disease was lower among pupils
      attending schools benefitting from school WASH improvements than students
      attending comparison schools. These findings support results from the parent
      study, which also found reduced incidence of self-reported diarrhea among pupils
      of beneficiary schools. DBS collection was feasible in this resource-poor field
      setting and provided objective evidence of disease at a low cost per antigen
      analyzed, making it an effective measurement tool for the WASH field. TRIAL
      REGISTRATION: The trial was registered at ClinicalTrials.gov (NCT01787058).

PMID- 29659575
TI  - Synergistic co-regulation and competition by a SOX9-GLI-FOXA phasic
      transcriptional network coordinate chondrocyte differentiation transitions.
AB  - The growth plate mediates bone growth where SOX9 and GLI factors control
      chondrocyte proliferation, differentiation and entry into hypertrophy. FOXA
      factors regulate hypertrophic chondrocyte maturation. How these factors integrate
      into a Gene Regulatory Network (GRN) controlling these differentiation
      transitions is incompletely understood. We adopted a genome-wide whole tissue
      approach to establish a Growth Plate Differential Gene Expression Library (GP
      DGEL) for fractionated proliferating, pre-hypertrophic, early and late
      hypertrophic chondrocytes, as an overarching resource for discovery of pathways
      and disease candidates. De novo motif discovery revealed the enrichment of SOX9
      and GLI binding sites in the genes preferentially expressed in proliferating and
      prehypertrophic chondrocytes, suggesting the potential cooperation between SOX9
      and GLI proteins. We integrated the analyses of the transcriptome, SOX9, GLI1 and
      GLI3 ChIP-seq datasets, with functional validation by transactivation assays and
      mouse mutants. We identified new SOX9 targets and showed SOX9-GLI directly and
      cooperatively regulate many genes such as Trps1, Sox9, Sox5, Sox6, Col2a1, Ptch1,
      Gli1 and Gli2. Further, FOXA2 competes with SOX9 for the transactivation of
      target genes. The data support a model of SOX9-GLI-FOXA phasic GRN in chondrocyte
      development. Together, SOX9-GLI auto-regulate and cooperate to activate and
      repress genes in proliferating chondrocytes. Upon hypertrophy, FOXA competes with
      SOX9, and control toward terminal differentiation passes to FOXA, RUNX, AP1 and
      MEF2 factors.

PMID- 29659576
TI  - The non-linear and lagged short-term relationship between rainfall and
      leptospirosis and the intermediate role of floods in the Philippines.
AB  - BACKGROUND: Leptospirosis is a worldwide bacterial zoonosis. Outbreaks of
      leptospirosis after heavy rainfall and flooding have been reported. However, few
      studies have formally quantified the effect of weather factors on leptospirosis
      incidence. We estimated the association between rainfall and leptospirosis cases
      in an urban setting in Manila, the Philippines, and examined the potential
      intermediate role of floods in this association. METHODS/PRINCIPAL FINDINGS:
      Relationships between rainfall and the weekly number of hospital admissions due
      to leptospirosis from 2001 to 2012 were analyzed using a distributed lag non
      linear model in a quasi-Poisson regression framework, controlling for seasonally
      varying factors other than rainfall. The role of floods on the rainfall
      leptospirosis relationship was examined using an indicator. We reported relative
      risks (RRs) by rainfall category based on the flood warning system in the
      country. The risk of post-rainfall leptospirosis peaked at a lag of 2 weeks
      (using 0 cm/week rainfall as the reference) with RRs of 1.30 (95% confidence
      interval: 0.99-1.70), 1.53 (1.12-2.09), 2.45 (1.80-3.33), 4.61 (3.30-6.43), and
      13.77 (9.10-20.82) for light, moderate, heavy, intense and torrential rainfall
      (at 2, 5, 16, 32 and 63 cm/week), respectively. After adjusting for floods, RRs
      (at a lag of 2 weeks) decreased at higher rainfall levels suggesting that flood
      is on the causal pathway between rainfall and leptospirosis. CONCLUSIONS:
      Rainfall was strongly associated with increased hospital admission for
      leptospirosis at a lag of 2 weeks, and this association was explained in part by
      floods.

PMID- 29659577
TI  - Transcription factor HAT1 is a substrate of SnRK2.3 kinase and negatively
      regulates ABA synthesis and signaling in Arabidopsis responding to drought.
AB  - Drought is a major threat to plant growth and crop productivity. The phytohormone
      abscisic acid (ABA) plays a critical role in plant response to drought stress.
      Although ABA signaling-mediated drought tolerance has been widely investigated in
      Arabidopsis thaliana, the feedback mechanism and components negatively regulating
      this pathway are less well understood. Here we identified a member of Arabidopsis
      HD-ZIP transcription factors HAT1 which can interacts with and be phosphorylated
      by SnRK2s. hat1hat3, loss-of-function mutant of HAT1 and its homolog HAT3, was
      hypersensitive to ABA in primary root inhibition, ABA-responsive genes
      expression, and displayed enhanced drought tolerance, whereas HAT1 overexpressing
      lines were hyposensitive to ABA and less tolerant to drought stress, suggesting
      that HAT1 functions as a negative regulator in ABA signaling-mediated drought
      response. Furthermore, expression levels of ABA biosynthesis genes ABA3 and NCED3
      were repressed by HAT1 directly binding to their promoters, resulting in the ABA
      level was increased in hat1hat3 and reduced in HAT1OX lines. Further evidence
      showed that both protein stability and binding activity of HAT1 was repressed by
      SnRK2.3 phosphorylation. Overexpressing SnRK2.3 in HAT1OX transgenic plant made a
      reduced HAT1 protein level and suppressed the HAT1OX phenotypes in ABA and
      drought response. Our results thus establish a new negative regulation mechanism
      of HAT1 which helps plants fine-tune their drought responses.

PMID- 29659578
TI  - Cell adhesion and fluid flow jointly initiate genotype spatial distribution in
      biofilms.
AB  - Biofilms are microbial collectives that occupy a diverse array of surfaces. It is
      well known that the function and evolution of biofilms are strongly influenced by
      the spatial arrangement of different strains and species within them, but how
      spatiotemporal distributions of different genotypes in biofilm populations
      originate is still underexplored. Here, we study the origins of biofilm genetic
      structure by combining model development, numerical simulations, and microfluidic
      experiments using the human pathogen Vibrio cholerae. Using spatial correlation
      functions to quantify the differences between emergent cell lineage segregation
      patterns, we find that strong adhesion often, but not always, maximizes the size
      of clonal cell clusters on flat surfaces. Counterintuitively, our model predicts
      that, under some conditions, investing in adhesion can reduce rather than
      increase clonal group size. Our results emphasize that a complex interaction
      between fluid flow and cell adhesiveness can underlie emergent patterns of
      biofilm genetic structure. This structure, in turn, has an outsize influence on
      how biofilm-dwelling populations function and evolve.

PMID- 29659580
TI  - Preprints in medical research: Progress and principles.
AB  - In this month's editorial, the PLOS Medicine Editors discuss the role of
      preprints in human health research and propose a 3-part framework for ensuring
      benefit.

PMID- 29659579
TI  - Replication-incompetent rabies virus vector harboring glycoprotein gene of
      lymphocytic choriomeningitis virus (LCMV) protects mice from LCMV challenge.
AB  - BACKGROUND: Lymphocytic choriomeningitis virus (LCMV) causes a variety of
      diseases, including asymptomatic infections, meningitis, and congenital
      infections in the fetus of infected mother. The development of a safe and
      effective vaccine against LCMV is imperative. This study aims to develop a new
      candidate vaccine against LCMV using a recombinant replication-incompetent rabies
      virus (RV) vector. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we have
      generated a recombinant deficient RV expressing the LCMV glycoprotein precursor
      (GPC) (RVDeltaP-LCMV/GPC) which is lacking the RV-P gene. RVDeltaP-LCMV/GPC is
      able to propagate only in cells expressing the RV-P protein. In contrast, the
      LCMV-GPC can be expressed in general cells, which do not express RV-P protein.
      The ability of RVDeltaP-LCMV/GPC to protect mice from LCMV infection and induce
      cellular immunity was assessed. Mice inoculated intraperitoneally with RVDeltaP
      LCMV/GPC showed higher survival rates (88.2%) than those inoculated with the
      parental recombinant RV-P gene-deficient RV (RVDeltaP) (7.7%) following a LCMV
      challenge. Neutralizing antibody (NAb) against LCMV was not induced, even in the
      sera of surviving mice. CD8+ T-cell depletion significantly reduced the survival
      rates of RVDeltaP-LCMV/GPC-inoculated mice after the LCMV challenge. These
      results suggest that CD8+ T cells play a major role in the observed protection
      against LCMV. In contrast, NAbs against RV were strongly induced in sera of mice
      inoculated with either RVDeltaP-LCMV/GPC or RVDeltaP. In safety tests, suckling
      mice inoculated intracerebrally with RVDeltaP-LCMV/GPC showed no symptoms.
      CONCLUSIONS/SIGNIFICANCE: These results show RVDeltaP-LCMV/GPC might be a
      promising candidate vaccine with dual efficacy, protecting against both RV and
      LCMV.

PMID- 29659582
TI  - Using pseudoalignment and base quality to accurately quantify microbial community
      composition.
AB  - Pooled DNA from multiple unknown organisms arises in a variety of contexts, for
      example microbial samples from ecological or human health research. Determining
      the composition of pooled samples can be difficult, especially at the scale of
      modern sequencing data and reference databases. Here we propose a novel method
      for taxonomic profiling in pooled DNA that combines the speed and low-memory
      requirements of k-mer based pseudoalignment with a likelihood framework that uses
      base quality information to better resolve multiply mapped reads. We apply the
      method to the problem of classifying 16S rRNA reads using a reference database of
      known organisms, a common challenge in microbiome research. Using simulations, we
      show the method is accurate across a variety of read lengths, with different
      length reference sequences, at different sample depths, and when samples contain
      reads originating from organisms absent from the reference. We also assess
      performance in real 16S data, where we reanalyze previous genetic association
      data to show our method discovers a larger number of quantitative trait
      associations than other widely used methods. We implement our method in the
      software Karp, for k-mer based analysis of read pools, to provide a novel
      combination of speed and accuracy that is uniquely suited for enhancing
      discoveries in microbial studies.

PMID- 29659581
TI  - An interplay between multiple sirtuins promotes completion of DNA replication in
      cells with short telomeres.
AB  - The evolutionarily-conserved sirtuin family of histone deacetylases regulates a
      multitude of DNA-associated processes. A recent genome-wide screen conducted in
      the yeast Saccharomyces cerevisiae identified Yku70/80, which regulate
      nonhomologous end-joining (NHEJ) and telomere structure, as being essential for
      cell proliferation in the presence of the pan-sirtuin inhibitor nicotinamide
      (NAM). Here, we show that sirtuin-dependent deacetylation of both histone H3
      lysine 56 and H4 lysine 16 promotes growth of yku70Delta and yku80Delta cells,
      and that the NAM sensitivity of these mutants is not caused by defects in DNA
      double-strand break repair by NHEJ, but rather by their inability to maintain
      normal telomere length. Indeed, our results indicate that in the absence of
      sirtuin activity, cells with abnormally short telomeres, e.g., yku70/80Delta or
      est1/2Delta mutants, present striking defects in S phase progression. Our data
      further suggest that early firing of replication origins at short telomeres
      compromises the cellular response to NAM- and genotoxin-induced replicative
      stress. Finally, we show that reducing H4K16ac in yku70Delta cells limits
      activation of the DNA damage checkpoint kinase Rad53 in response to replicative
      stress, which promotes usage of translesion synthesis and S phase progression.
      Our results reveal a novel interplay between sirtuin-mediated regulation of
      chromatin structure and telomere-regulating factors in promoting timely
      completion of S phase upon replicative stress.

PMID- 29659583
TI  - A modelling approach for exploring muscle dynamics during cyclic contractions.
AB  - Hill-type muscle models are widely used within the field of biomechanics to
      predict and understand muscle behaviour, and are often essential where muscle
      forces cannot be directly measured. However, these models have limited accuracy,
      particularly during cyclic contractions at the submaximal levels of activation
      that typically occur during locomotion. To address this issue, recent studies
      have incorporated effects into Hill-type models that are oftentimes neglected,
      such as size-dependent, history-dependent, and activation-dependent effects.
      However, the contribution of these effects on muscle performance has yet to be
      evaluated under common contractile conditions that reflect the range of
      activations, strains, and strain rates that occur in vivo. The purpose of this
      study was to develop a modelling framework to evaluate modifications to Hill-type
      muscle models when they contract in cyclic loops that are typical of locomotor
      muscle function. Here we present a modelling framework composed of a damped
      harmonic oscillator in series with a Hill-type muscle actuator that consists of a
      contractile element and parallel elastic element. The intrinsic force-length and
      force-velocity properties are described using Bezier curves where we present a
      system to relate physiological parameters to the control points for these curves.
      The muscle-oscillator system can be geometrically scaled while preserving dynamic
      and kinematic similarity to investigate the muscle size effects while controlling
      for the dynamics of the harmonic oscillator. The model is driven by time-varying
      muscle activations that cause the muscle to cyclically contract and drive the
      dynamics of the harmonic oscillator. Thus, this framework provides a platform to
      test current and future Hill-type model formulations and explore factors
      affecting muscle performance in muscles of different sizes under a range of
      cyclic contractile conditions.

PMID- 29659584
TI  - Long-term survival of patients with thyroid cancer according to the methods of
      tumor detection: A nationwide cohort study in Korea.
AB  - In this retrospective cohort study, we compared the survival of patients detected
      by screening with those detected based on symptoms, according to their tumor
      stages. After propensity score matching, 2,130 patients with papillary or
      follicular thyroid cancer, identified by screening detection (SD) and clinical
      detection (CD), were included. We compared the survival rates of patients
      identified by SD and CD in the early and advanced stages of thyroid cancer. Cox
      proportional hazard models were used to compare the hazard ratios (HRs) for
      mortality between the two groups. Of the 1,065 patients in each group, 12 (1.1%)
      died in the SD group, compared to 44 (4.1%) in the CD group, during an average
      9.4 years (p<0.001). For early stage, there was no significant difference in all
      cause and thyroid cancer-specific mortality between the two groups (p = 0.08, p =
      0.0502). However, for advanced stage, the survival rates in the SD group were
      significantly higher than in the CD group (p<0.001, p = 0.004). Moreover, after
      adjusting for covariates, the HRs of all-cause mortality of the SD group was
      significantly lower than that of the CD group for the advanced stage patients
      (HRs: 0.37 [95% CIs: 0.17-0.80]), while no significant difference was observed in
      the early stage. While screening for thyroid cancer was not beneficial for early
      stage patients, our findings suggest that detection via screening is associated
      with better survival for patients with advanced stage cancer. However, the
      effects of selection bias and lead time bias could not be entirely excluded.

PMID- 29659585
TI  - Protective effect of nicorandil on myocardial injury following percutaneous
      coronary intervention in older patients with stable coronary artery disease:
      Secondary analysis of a randomized, controlled trial (RINC).
AB  - BACKGROUND: Our previous study examined an effect of remote ischemic
      preconditioning (RIPC) or intravenous nicorandil on reduction of periprocedural
      myocardial injury (pMI) following percutaneous coronary intervention (PCI) in
      patients with stable coronary artery disease (CAD). We further investigated the
      effect of RIPC or nicorandil on pMI in older patients. METHODS: Patients with
      stable CAD who planned to undergo PCI were assigned to a 1:1:1 ratio to control,
      intravenous nicorandil, or upper-limb RIPC groups. This substudy analyzed
      patients aged >65 years (n = 282) from the principal cohort. The primary outcome
      was the incidence of pMI following PCI. We defined pMI as an elevated level of
      high-sensitive cardiac troponin T or creatine kinase myocardial band 12 or 24
      hours after PCI. RESULTS: We found that pMI following PCI was significantly
      reduced in the nicorandil group compared with the control group (37.2% vs. 53.7%,
      multiplicity-adjusted p = 0.046), but not in the RIPC group compared with the
      control group (43.0% vs. 53.7%, multiplicity-adjusted p = 0.245). The adjusted
      odds ratios (95% confidence interval) for pMI in the RIPC and nicorandil groups
      versus the control group were 0.63 (0.34 to 1.16) and 0.51 (0.27 to 0.96),
      respectively. CONCLUSION: Intravenous nicorandil significantly reduces pMI
      following PCI in a subgroup of older patients with stable CAD. Phase 3 trials are
      required to validate our results. TRIAL REGISTRATION: UMIN Clinical Trials
      Registry UMIN000005607.

PMID- 29659586
TI  - Supply-side interventions to improve health: Findings from the Salud Mesoamerica
      Initiative.
AB  - BACKGROUND: Results-based aid (RBA) is increasingly used to incentivize action in
      health. In Mesoamerica, the region consisting of southern Mexico and Central
      America, the RBA project known as the Salud Mesoamerica Initiative (SMI) was
      designed to target disparities in maternal and child health, focusing on the
      poorest 20% of the population across the region. METHODS AND FINDINGS: Data were
      first collected in 365 intervention health facilities to establish a baseline of
      indicators. For the first follow-up measure, 18 to 24 months later, 368
      facilities were evaluated in these same areas. At both stages, we measured a near
      identical set of supply-side performance indicators in line with country-specific
      priorities in maternal and child health. All countries showed progress in
      performance indicators, although with different levels. El Salvador, Honduras,
      Nicaragua, and Panama reached their 18-month targets, while the State of Chiapas
      in Mexico, Guatemala, and Belize did not. A second follow-up measurement in
      Chiapas and Guatemala showed continued progress, as they achieved previously
      missed targets nine to 12 months later, after implementing a performance
      improvement plan. CONCLUSIONS: Our findings show an initial success in the supply
      side indicators of SMI. Our data suggest that the RBA approach can be a motivator
      to improve availability of drugs and services in poor areas. Moreover, our
      innovative monitoring and evaluation framework will allow health officials with
      limited resources to identify and target areas of greatest need.

PMID- 29659588
TI  - Effects of mTOR-Is on malignancy and survival following renal transplantation: A
      systematic review and meta-analysis of randomized trials with a minimum follow-up
      of 24 months.
AB  - BACKGROUND: mTOR-Is positively influence the occurrence and course of certain
      tumors after solid organ transplantation. The effect of mTOR-Is on the overall
      incidence of tumors irrespective of their origin is not entirely clear.
      Furthermore, conflicting data have been shown on mortality under mTOR-Is.
      METHODS: The current literature was searched for prospective randomized
      controlled renal transplantation trials. There were 1415 trials screened of which
      13 could be included (pts. = 5924). A minimum follow-up of 24 months was
      mandatory for inclusion. Incidence of malignancies and patient survival was
      assessed in meta-analyses. RESULTS: The average follow-up of all trials was 40.6
      months. Malignancy was significantly reduced under mTOR-Is compared to CNIs (RR
      0.70, CI 0.49-0.99, p = 0.046). This effect remained stable when combined with
      CNIs (RR 0.58, CI 0.34-1.00, p = 0.05). When NMSCs were excluded the risk for
      malignancy remained significantly reduced under mTOR-I therapy (mono and combi)
      (RR 0.43, CI 0.24-0.77, p = 0.0046). Graft survival was minimally decreased under
      mTOR-Is (RR 0.99, CI 0.98-1.00, p = 0.054). This effect was abrogated when mTOR
      Is were combined with CNIs (RR 0.99, CI 0.97-1.02, p = 0.50). Patient survival
      was not different (RR 1.00, CI 0.99-1.01, p = 0.54). CONCLUSIONS: Posttransplant
      patients have a lower incidence of malignancy when treated with an mTOR-I no
      matter if it is used in combination with CNIs or not. This beneficial effect
      remains significant even when NMSCs are excluded. With currently used mTOR-I
      based regimen patient and graft survival is not different compared to CNI
      therapies.

PMID- 29659587
TI  - Can chimerism explain breast/ovarian cancers in BRCA non-carriers from BRCA
      positive families?
AB  - Hereditary breast and ovarian cancer syndrome (HBOC) is most frequently caused by
      mutations in BRCA1 or BRCA2 (in short, BRCA) genes. The incidence of hereditary
      breast and ovarian cancer in relatives of BRCA mutation carriers who test
      negative for the familial mutation (non-carriers) may be increased. However, the
      data is controversial, and at this time, these individuals are recommended the
      same cancer surveillance as general population. One possible explanation for BRCA
      phenocopies (close relatives of BRCA carriers who have developed cancer
      consistent with HBOC but tested negative for a familial mutation) is natural
      chimerism where lack of detectable mutation in blood may not rule out the
      presence of the mutation in the other tissues. To test this hypothesis, archival
      tumor tissue from eleven BRCA phenocopies was investigated. DNA from the tumor
      tissue was analyzed using sequence-specific PCR, capillary electrophoresis, and
      pyrosequencing. The familial mutations were originally detected in the patients'
      first-degree relatives by commercial testing. The same testing detected no
      mutations in the blood of the patients under study. The test methods targeted
      only the known familial mutation in the tumor tissue. Tumor diagnoses included
      breast, ovarian, endometrial and primary peritoneal carcinoma. None of the
      familial mutations were found in the tumor samples tested. These results do not
      support, but do not completely exclude, the possibility of chimerism in these
      patients. Further studies with comprehensive sequence analysis in a larger
      patient group are warranted as a chimeric state would further refine the
      predictive value of genetic testing to include BRCA phenocopies.

PMID- 29659589
TI  - Correlation between physical markers and psychiatric health in a Portuguese
      systemic lupus erythematosus cohort: The role of suffering in chronic autoimmune
      disease.
AB  - BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease
      that affects a large number of people throughout the world. Anxiety, depression
      and fatigue are common symptoms of SLE that substantially contribute to decreased
      quality of life. This study investigates the interplay between physical and
      psychiatric manifestations of lupus. To this end, an SLE patient cohort was
      examined for correlations between clinical presentation, laboratory tests, and
      psychological indicators. METHODS: Seventy-two lupus patients were evaluated for
      psychological status using a battery of instruments, including assessments for
      fatigue (CFS & FSS), depression (HADS), anxiety (HADS), overall health (SF-36 &
      PSQI) and intimate relationship satisfaction (RAS & CSI). Scores from these
      assessments were correlated with lupus clinical profiles and laboratory test
      values. RESULTS: The prevalence of depression in the SLE patient cohort was
      41.7%, as measured by the hospital depression and anxiety scale. The study
      identified that pain (p = 0.001), body mass index (p = 0.026), Chalder's fatigue
      scale (p < 0.001), fatigue severity scale (p < 0.001), and anxiety (p = 0.001)
      are all positively correlated with depression in SLE patients. Total complement
      (CH50) (p = 0.032), and SF-36 physical and mental characteristic assessments are
      negatively correlated with depression. Longitudinal analysis indicated that the
      disease related complaint alopecia (p = 0.008) and relationship assessment scale
      scores (p = 0.004) may also be correlated to depression in SLE patients.
      Multivariant scrutiny of the clinical and psychosocial characteristics identified
      the fatigue severity scale (p = 0.026), SF-36 physical function (p = 0.040),
      physical role function (0.030), and mental health (p = 0.002) as the best
      indicators directly correlated with depression for the SLE cohort. CONCLUSION:
      These results reveal the influence of physical manifestations of lupus including
      fatigue, pain, body mass index and anxiety, as well as decreased physical and
      mental function, on depression. Fatigue is the strongest factor correlated with
      depression in SLE patients in the cohort. Both physical and social/psychological
      aspects likely contribute to the depression and anxiety in lupus.

PMID- 29659590
TI  - Organic cultivation of Ashwagandha with improved biomass and high content of
      active Withanolides: Use of Vermicompost.
AB  - Withania somnifera (Ashwagandha) has recently been studied extensively for its
      health-supplementing and therapeutic activities against a variety of ailments.
      Several independent studies have experimentally demonstrated pharmaceutical
      potential of its active Withanolides, Withaferin A (Wi-A), Withanone (Wi-N) and
      Withanolide A (Wil-A). However, to promote its use in herbal industry, an
      environmentally sustainable cultivation and high yield are warranted. In modern
      agriculture strategies, there has been indiscriminate use of chemical fertilizers
      to boost the crop-yield, however the practice largely ignored its adverse effect
      on the quality of soil and the environment. In view of these, we attempted to
      recruit Vermicompost (Vcom, 20-100%) as an organic fertilizer of choice during
      the sowing and growing phases of Ashwagandha plants. We report that (i) pre
      soaking of seeds for 12 h in Vermicompost leachate (Vcom-L) and Vermicompost tea
      (Vcom-T) led to higher germination, (ii) binary combination of pre-soaking of
      seeds and cultivation in Vcom (up to 80%) resulted in further improvement both in
      germination and seedling growth, (iii) cultivated plants in the presence of
      Vcom+Vcom-L showed higher leaf and root mass, earlier onset of flowering and
      fruiting and (iv) leaves from the Vcom+Vcom-L cultivated plants showed higher
      level of active Withanolides, Withanone (Wi-N), Withanolide A (Wil-A) and
      Withaferin A (Wi-A) and showed anticancer activities in cell culture assays.
      Taken together, we report a simple and inexpensive method for improving the yield
      and pharmaceutical components of Ashwagandha leaves.

PMID- 29659591
TI  - Does interferon-free direct-acting antiviral therapy for hepatitis C after
      curative treatment for hepatocellular carcinoma lead to unexpected recurrences of
      HCC? A multicenter study by the Japanese Red Cross Hospital Liver Study Group.
AB  - BACKGROUND AND AIM: This study aimed to elucidate whether interferon (IFN)-free
      direct-acting antiviral (DAA) therapy for hepatitis C after curative treatment of
      hepatocellular carcinoma (HCC) promotes HCC recurrence in a real-world large
      scale cohort. METHODS: This multicenter study was conducted by the Japanese Red
      Cross Hospital Liver Study Group. This retrospective study analyzed 516 patients
      who underwent antiviral treatment for hepatitis C with either IFN (n = 148) or
      IFN-free DAA (n = 368) after curative HCC treatment; 78 IFN-treated patients and
      347 IFN-free DAA-treated patients achieved sustained virological response (SVR).
      The recurrence rate of HCC was compared between the antiviral therapies. Logistic
      analysis and Cox proportional hazards analysis identified factors associated with
      early recurrence of HCC within 24 weeks of antiviral therapy and recurrence
      throughout the observation period, respectively. RESULTS: AFP at the completion
      of antiviral therapy, clinical stage of HCC, and non-SVR were independent factors
      associated with early recurrence of HCC. Among patients who had achieved SVR, the
      clinical stage of HCC and the level of AFP at completion of antiviral therapy
      were independent factors associated with early recurrence of HCC. For recurrence
      throughout the observation period in SVR patients, AFP at completion of antiviral
      therapy, duration between last HCC treatment to antiviral therapy, and the number
      of treatments were independent factors. There was no significant difference in
      the rate of early recurrence of HCC or recurrence throughout the observation
      period between IFN and IFN-free DAA treated patients. CONCLUSIONS: There were no
      differences in the early recurrence rate of HCC between patients who underwent
      IFN and those who underwent IFN-free DAA as antiviral therapies.

PMID- 29659592
TI  - Motor (but not auditory) attention affects syntactic choice.
AB  - Understanding the determinants of syntactic choice in sentence production is a
      salient topic in psycholinguistics. Existing evidence suggests that syntactic
      choice results from an interplay between linguistic and non-linguistic factors,
      and a speaker's attention to the elements of a described event represents one
      such factor. Whereas multimodal accounts of attention suggest a role for
      different modalities in this process, existing studies examining attention
      effects in syntactic choice are primarily based on visual cueing paradigms.
      Hence, it remains unclear whether attentional effects on syntactic choice are
      limited to the visual modality or are indeed more general. This issue is
      addressed by the current study. Native English participants viewed and described
      line drawings of simple transitive events while their attention was directed to
      the location of the agent or the patient of the depicted event by means of either
      an auditory (monaural beep) or a motor (unilateral key press) lateral cue. Our
      results show an effect of cue location, with participants producing more passive
      voice descriptions in the patient-cued conditions. Crucially, this cue location
      effect emerged in the motor-cue but not (or substantially less so) in the
      auditory-cue condition, as confirmed by a reliable interaction between cue
      location (agent vs. patient) and cue type (auditory vs. motor). Our data suggest
      that attentional effects on the speaker's syntactic choices are modality-specific
      and limited to the visual and motor, but not the auditory, domain.

PMID- 29659593
TI  - The complexity of patients hospitalized in Internal Medicine wards evaluated by
      FADOI-COMPLIMED score(s). A hypothetical approach.
AB  - OBJECTIVES: The aim of this study is to develop a new predictive model to measure
      complexity of patients in medical wards. SETTING: 29 Internal Medicine
      departments in Italy. MATERIALS AND METHODS: The study cohort was made of 541
      consecutive patients hospitalized for any cause, aged more than 40 years and with
      at least two chronic diseases. First, we applied a hierarchical cluster analysis
      and the principal component analysis (PCA) to a panel of questionnaires
      [comorbidity (Charlson, CIRS), clinical stability (MEWS), social frailty
      (Flugelman), cognitive dysfunction (SPSMQ), depression (5-item GDS), functional
      dependence (ADL, IADL, Barthel), risk of sore threats (Exton-Smith scale),
      nutrition (MNA), pain (NRPS), adherence to therapy (Morisky scale)], in order to
      select domains informative for the definition of complexity. The following step
      was to create the score(s) needed to quantify it. RESULTS: Two main clusters were
      identified: the first includes 7 questionnaires whose common denominator is
      dependence and frailty, the second consists of 3 questionnaires representative of
      comorbidity. Globally, they account for about 70% of the total variance (55.2%
      and 13.8%, respectively). The first principal component was simplified in
      "Complimed Score 1" (CS1) as a recalibrated average between the Barthel Index and
      the Exton Smith score, whereas the second cluster was approximated to "Complimed
      Score 2" (CS2), by using the Charlson score only. CONCLUSIONS: Complexity is a
      two-dimensional clinical phenomenon. The FADOI-Complimed Score(s) is a new tool
      useful for the routine evaluation of complexity in medical patients, simple to
      use and taking around 10 minutes to complete.

PMID- 29659594
TI  - Determining carnivore habitat use in a rubber/forest landscape in Brazil using
      multispecies occupancy models.
AB  - Understanding the factors that influence the presence and distribution of
      carnivores in human-dominated agricultural landscapes is one of the main
      challenges for biodiversity conservation, especially in landscapes where setting
      aside large protected areas is not feasible. Habitat use models of carnivore
      communities in rubber plantations are lacking despite the critical roles
      carnivores play in structuring ecosystems and the increasing expansion of rubber
      plantations. We investigated the habitat use of a mammalian carnivore community
      within a 4,200-ha rubber plantation/forest landscape in Bahia, Brazil. We placed
      two different brands of camera traps in a 90-site grid. We used a multispecies
      occupancy model to determine the probabilities of habitat use by each species and
      the effect of different brands of camera traps on their detection probabilities.
      Species showed significant differences in habitat use with domestic dogs (Canis
      familiaris) and crab-eating foxes (Cerdocyon thous) having higher probabilities
      of using rubber groves and coatis (Nasua nasua) having a higher probability of
      using forest. The moderate level of captures and low detection probabilities (<=
      0.1) of tayras (Eira barbara) and wildcats (Leopardus spp.) precluded a precise
      estimation of habitat use probabilities using the multispecies occupancy model.
      The different brands of camera traps had a significant effect on the detection
      probability of all species. Given that the carnivore community has persisted in
      this 70-year-old landscape, the results show the potential of rubber/forest
      landscapes to provide for the long-term conservation of carnivore communities in
      the Atlantic forest, especially in mosaics with 30-40% forest cover and guard
      patrolling systems. The results also provide insights for mitigating the impact
      of rubber production on biodiversity.

PMID- 29659595
TI  - Emotional and economic intimate partner violence as key drivers of depression and
      suicidal ideation: A cross-sectional study among young women in informal
      settlements in South Africa.
AB  - TRIAL REGISTRATION: NCT03022370. Registered 13 January 2017, retrospectively
      registered.

PMID- 29659596
TI  - Universal expression for the drag on a fluid sphere.
AB  - An expression was developed for prediction of drag coefficients for any spherical
      particle, drop or bubble in an infinite, homogeneous liquid. The formula
      reproduces the limiting cases for gas bubbles and solid spheres, as well as the
      exact Hadamard-Rybczynski solution. The accuracy of the expression, which is
      valid for Reynolds numbers up to a few hundred, was confirmed by comparison with
      published numerical predictions of the drag coefficient for a range of physical
      circumstances.

PMID- 29659597
TI  - Measuring movement into residential care institutions in Haiti after Hurricane
      Matthew: A pilot study.
AB  - BACKGROUND: Governments have an ethical imperative to safeguard children in
      residential care institutions at all times, including in the aftermath of an
      emergency. Yet, a lack of accurate data about how the magnitude and
      characteristics of this population may change due to an emergency impedes
      leaders' ability to formulate responsive policies and services, mobilize
      resources and foster accountability. The purpose of this study was therefore to
      determine the feasibility of evaluating movement of children into residential
      care following an emergency. METHODS: The pilot study took place in Les Cayes
      commune in the Sud Department of Haiti in April 2017. Six months prior to the
      pilot, the area was severely affected by Hurricane Matthew, with widespread
      devastation to property, livestock and livelihoods. Using a two-stage process,
      the team created a comprehensive list of residential care institutions in Les
      Cayes. At each facility, the data collectors attempted to administer four
      separate tools: a group count tool, a record review tool, interviews with staff,
      and interviews with children 10 years of age and older. RESULTS: Out of 27 known
      institutions in Les Cayes, 22 institutions consented to participate in the
      research. Within these 22 institutions, the prevalence of new arrivals to
      residential care since Hurricane Matthew varied significantly across the four
      tools, ranging from 0.69% according to the aggregated child interviews to 20.96%
      according to the aggregated staff interviews. Record availability and quality was
      very poor and child participation was difficult to arrange due to travel and
      scheduling constraints. INTERPRETATION: Robust measurement of new arrivals to
      residential care institutions was not feasible in Haiti following Hurricane
      Matthew. Moreover, many of the challenges encountered are likely to be
      encountered in humanitarian emergencies in other settings. Therefore, the
      research team does not recommend scale-up of these methods in most humanitarian
      settings. Alternative approaches that incorporate household survey methods to
      ascertain movement into residential care based on reports from caregivers may be
      more realistic in places with poor pre-existing governance systems and weak
      registries and records for residential care institutions.

PMID- 29659598
TI  - Reducing health inequalities with interventions targeting behavioral factors
      among individuals with low levels of education - A rapid review.
AB  - Individuals with low levels of education systematically have worse health than
      those with medium or high levels of education. Yet there are few examples of
      attempts to summarize the evidence supporting the efficacy of interventions
      targeting health-related behavior among individuals with low education levels,
      and a large part of the literature is descriptive rather than analytical. A rapid
      review was carried out to examine the impact of such interventions. Special
      attention was given to the relative impact of the interventions among individuals
      with low education levels and their potential to reduce health inequality. Of
      1,365 articles initially identified, only 31 were deemed relevant for the review,
      and of those, nine met the inclusion and quality criteria. The comparability of
      included studies was limited due to differences in study design, sample
      characteristics, and definitions of exposure and outcome variables. Therefore,
      instead of performing a formal meta-analysis, an overall assessment of the
      available evidence was made and summarized into some general conclusions. We
      found no support for the notion that the methods used to reduce smoking decrease
      inequalities in health between educational groups. Evidence was also limited for
      decreasing inequality through interventions regarding dietary intake, physical
      activity and mental health. Only one study was found using an intervention
      designed to decrease socioeconomic inequalities by increasing the use of breast
      cancer screening. Thus, we concluded that there is a lack of support regarding
      this type of intervention as well. Therefore, the main conclusion is that solid
      evidence is lacking for interventions aimed at individual determinants of health
      and that more research is needed to fill this gap in knowledge.

PMID- 29659599
TI  - Profiling extracellular vesicle release by the filarial nematode Brugia malayi
      reveals sex-specific differences in cargo and a sensitivity to ivermectin.
AB  - The filarial nematode Brugia malayi is an etiological agent of Lymphatic
      Filariasis. The capability of B. malayi and other parasitic nematodes to modulate
      host biology is recognized but the mechanisms by which such manipulation occurs
      are obscure. An emerging paradigm is the release of parasite-derived
      extracellular vesicles (EV) containing bioactive proteins and small RNA species
      that allow secretion of parasite effector molecules and their potential
      trafficking to host tissues. We have previously described EV release from the
      infectious L3 stage B. malayi and here we profile vesicle release across all
      intra-mammalian life cycle stages (microfilariae, L3, L4, adult male and female
      worms). Nanoparticle Tracking Analysis was used to quantify and size EVs
      revealing discrete vesicle populations and indicating a secretory process that is
      conserved across the life cycle. Brugia EVs are internalized by murine
      macrophages with no preference for life stage suggesting a uniform mechanism for
      effector molecule trafficking. Further, the use of chemical uptake inhibitors
      suggests all life stage EVs are internalized by phagocytosis. Proteomic profiling
      of adult male and female EVs using nano-scale LC-MS/MS described quantitative and
      qualitative differences in the adult EV proteome, helping define the biogenesis
      of Brugia EVs and revealing sexual dimorphic characteristics in immunomodulatory
      cargo. Finally, ivermectin was found to rapidly inhibit EV release by all Brugia
      life stages. Further this drug effect was also observed in the related filarial
      nematode, the canine heartworm Dirofilaria immitis but not in an ivermectin
      unresponsive field isolate of that parasite, highlighting a potential mechanism
      of action for this drug and suggesting new screening platforms for anti-filarial
      drug development.

PMID- 29659602
TI  - A direct Primitive Variable Recovery Scheme for hyperbolic conservative
      equations: The case of relativistic hydrodynamics.
AB  - In this article we develop a Primitive Variable Recovery Scheme (PVRS) to solve
      any system of coupled differential conservative equations. This method obtains
      directly the primitive variables applying the chain rule to the time term of the
      conservative equations. With this, a traditional finite volume method for the
      flux is applied in order avoid violation of both, the entropy and "Rankine
      Hugoniot" jump conditions. The time evolution is then computed using a forward
      finite difference scheme. This numerical technique evades the recovery of the
      primitive vector by solving an algebraic system of equations as it is often used
      and so, it generalises standard techniques to solve these kind of coupled
      systems. The article is presented bearing in mind special relativistic
      hydrodynamic numerical schemes with an added pedagogical view in the appendix
      section in order to easily comprehend the PVRS. We present the convergence of the
      method for standard shock-tube problems of special relativistic hydrodynamics and
      a graphical visualisation of the errors using the fluctuations of the numerical
      values with respect to exact analytic solutions. The PVRS circumvents the
      sometimes arduous computation that arises from standard numerical methods
      techniques, which obtain the desired primitive vector solution through an
      algebraic polynomial of the charges.

PMID- 29659600
TI  - Reconstruction of a 10-mm-long median nerve gap in an ischemic environment using
      autologous conduits with different patterns of blood supply: A comparative study
      in the rat.
AB  - The aim of this study was to evaluate in the Wistar rat the efficacy of various
      autologous nerve conduits with various forms of blood supply in reconstructing a
      10-mm-long gap in the median nerve (MN) under conditions of local ischemia. A 10
      mm-long median nerve defect was created in the right arm. A loose silicone tube
      was placed around the nerve gap zone, in order to simulate a local ischemic
      environment. Rats were divided in the following experimental groups (each with 20
      rats): the nerve Graft (NG) group, in which the excised MN segment was
      reattached; the conventional nerve flap (CNF) and the arterialized neurovenous
      flap (ANVF) groups in which the gap was bridged with homonymous median nerve
      flaps; the prefabricated nerve flap (PNF) group in which the gap was
      reconstructed with a fabricated flap created by leaving an arteriovenous fistula
      in contact with the sciatic nerve for 5 weeks; and the two control groups, Sham
      and Excision groups. In the latter group, the proximal stump of the MN nerve was
      ligated and no repair was performed. The rats were followed for 100 days. During
      this time, they did physiotherapy. Functional, electroneuromyographic and
      histological studies were performed. The CNF and ANVF groups presented better
      results than the NG group in the following assessments: grasping test,
      nociception, motor stimulation threshold, muscle weight, and histomorphometric
      evaluation. Radial deviation of the operated forepaw was more common in rats that
      presented worse results in the other outcome variables. Overall, CNFs and ANVFs
      produced a faster and more complete recovery than NGs in the reconstruction of a
      10-mm-long median nerve gap in an ischemic environment in the Wistar rat.
      Although, results obtained with CNFs were in most cases were better than ANVFs,
      these differences were not statistically significant for most of the outcome
      variables.

PMID- 29659601
TI  - In vitro assessment of cytotoxic activities of Lachesis muta muta snake venom.
AB  - Envenomation by the bushmaster snake Lachesis muta muta is considered severe,
      characterized by local effects including necrosis, the main cause of permanent
      disability. However, cellular mechanisms related to cell death and tissue
      destruction, triggered by snake venoms, are poorly explored. The purpose of this
      study was to investigate the cytotoxic effect caused by L. m. muta venom in
      normal human keratinocytes and to identify the cellular processes involved in in
      cellulo envenomation. In order to investigate venom effect on different cell
      types, Alamar Blue assay was performed to quantify levels of cellular metabolism
      as a readout of cell viability. Apoptosis, necrosis and changes in mitochondrial
      membrane potential were evaluated by flow cytometry, while induction of autophagy
      was assessed by expression of GFP-LC3 and analyzed using fluorescence microscopy.
      The cytotoxic potential of the venom is shown by reduced cell viability in a
      concentration-dependent manner. It was also observed the sequential appearance of
      cells undergoing autophagy (by 6 hours), apoptosis and necrosis (12 and 24
      hours). Morphologically, incubation with L. m. muta venom led to a significant
      cellular retraction and formation of cellular aggregates. These results indicate
      that L. m. muta venom is cytotoxic to normal human keratinocytes and other cell
      lines, and this toxicity involves the integration of distinct modes of cell
      death. Autophagy as a cell death mechanism, in addition to apoptosis and
      necrosis, can help to unravel cellular pathways and mechanisms triggered by the
      venom. Understanding the mechanisms that underlie cellular damage and tissue
      destruction will be useful in the development of alternative therapies against
      snakebites.

PMID- 29659603
TI  - Genetic diversity and distribution of Senegalia senegal (L.) Britton under
      climate change scenarios in West Africa.
AB  - Climate change is predicted to impact species' genetic diversity and
      distribution. We used Senegalia senegal (L.) Britton, an economically important
      species distributed in the Sudano-Sahelian savannah belt of West Africa, to
      investigate the impact of climate change on intraspecific genetic diversity and
      distribution. We used ten nuclear and two plastid microsatellite markers to
      assess genetic variation, population structure and differentiation across
      thirteen sites in West Africa. We projected suitable range, and potential impact
      of climate change on genetic diversity using a maximum entropy approach, under
      four different climate change scenarios. We found higher genetic and haplotype
      diversity at both nuclear and plastid markers than previously reported. Genetic
      differentiation was strong for chloroplast and moderate for the nuclear genome.
      Both genomes indicated three spatially structured genetic groups. The
      distribution of Senegalia senegal is strongly correlated with extractable
      nitrogen, coarse fragments, soil organic carbon stock, precipitation of warmest
      and coldest quarter and mean temperature of driest quarter. We predicted 40.96 to
      6.34 per cent of the current distribution to favourably support the species'
      ecological requirements under future climate scenarios. Our results suggest that
      climate change is going to affect the population genetic structure of Senegalia
      senegal, and that patterns of genetic diversity are going to influence the
      species' adaptive response to climate change. Our study contributes to the
      growing evidence predicting the loss of economically relevant plants in West
      Africa in the next decades due to climate change.

PMID- 29659604
TI  - Similarity in replication timing between polytene and diploid cells is associated
      with the organization of the Drosophila genome.
AB  - Morphologically, polytene chromosomes of Drosophila melanogaster consist of
      compact "black" bands alternating with less compact "grey" bands and interbands.
      We developed a comprehensive approach that combines cytological mapping data of
      FlyBase-annotated genes and novel tools for predicting cytogenetic features of
      chromosomes on the basis of their protein composition and determined the genomic
      coordinates for all black bands of polytene chromosome 2R. By a PCNA
      immunostaining assay, we obtained the replication timetable for all the bands
      mapped. The results allowed us to compare replication timing between polytene
      chromosomes in salivary glands and chromosomes from cultured diploid cell lines
      and to observe a substantial similarity in the global replication patterns at the
      band resolution level. In both kinds of chromosomes, the intervals between black
      bands correspond to early replication initiation zones. Black bands are depleted
      of replication initiation events and are characterized by a gradient of
      replication timing; therefore, the time of replication completion correlates with
      the band length. The bands are characterized by low gene density, contain
      predominantly tissue-specific genes, and are represented by silent chromatin
      types in various tissues. The borders of black bands correspond well to the
      borders of topological domains as well as to the borders of the zones showing
      H3K27me3, SUUR, and LAMIN enrichment. In conclusion, the characteristic pattern
      of polytene chromosomes reflects partitioning of the Drosophila genome into two
      global types of domains with contrasting properties. This partitioning is
      conserved in different tissues and determines replication timing in Drosophila.

PMID- 29659606
TI  - Humoral immunity to memory antigens and pathogens is maintained in patients with
      chronic kidney disease.
AB  - Patients with chronic kidney disease (CKD) have an increased risk of infection
      and poorer responses to vaccination. This suggests that CKD patients have an
      impaired responsiveness to all antigens, even those first encountered before CKD
      onset. To examine this we evaluated antibody responses against two childhood
      vaccine antigens, tetanus (TT) and diphtheria toxoids (DT) and two common
      pathogens, cytomegalovirus (CMV) and Salmonella enterica serovar Enteritidis
      (SEn) in two independent cohorts consisting of age-matched individuals with and
      without CKD. Sera were evaluated for antigen-specific IgG titres and the
      functionality of antibody to SEn was assessed in a serum bactericidal assay.
      Surprisingly, patients with CKD and control subjects had comparable levels of IgG
      against TT and DT, suggesting preserved humoral memory responses to antigens
      encountered early in life. Lipopolysaccharide-specific IgG titres and serum
      bactericidal activity in patients with CKD were also not inferior to controls.
      CMV-specific IgG titres in seropositive CKD patients were similar or even
      increased compared to controls. Therefore, whilst responses to new vaccines in
      CKD are typically lower than expected, antibody responses to antigens commonly
      encountered prior to CKD onset are not. The immunodeficiency of CKD is likely
      characterised by failure to respond to new antigenic challenges and efforts to
      improve patient outcomes should be focussed here.

PMID- 29659607
TI  - Phenotypic plasticity of pre-adult egg maturation in a parasitoid: Effects of
      host-starvation and brood size.
AB  - Larvae of parasitoid wasps develop on a single arthropod host, and often face
      resource limitation that induces a tradeoff between egg maturation and somatic
      growth. Part of the variation in the growth-reproduction allocation was shown to
      be heritable, but how the larval developmental environment affects this
      allocation is not well-known. Detection of life history tradeoffs is often
      facilitated under stress conditions. We therefore exposed developing female
      larvae of the polyembryonic parasitoid Copidosoma koehleri (Hymenoptera:
      Encyrtidae) to laboratory manipulations aimed to restrict host resources (either
      host-starvation or high larval density). We compared the females' body sizes and
      egg loads shortly after adult emergence (<24 h) to those of closely related
      control females, which developed at a lower larval density within non-starved
      hosts. Host-starvation reduced the females' body sizes but not their initial egg
      loads. Females that experienced high larval density produced more eggs but were
      similar in body size to the low-density controls. Thus, the relative allocation
      to reproduction increased in response to both manipulations of host condition.
      Developmental duration and longevity were similar in all treatments. The negative
      correlation between body size and reproductive allocation, observed in the host
      starvation treatment, is compatible with previous evidence from other
      parasitoids. In the high larval density treatment, however, reproductive
      allocation increased while body size was maintained, suggesting that the higher
      density increased rather than limited host resources per developing parasitoid
      female. The additional host resources that were diverted into egg production
      possibly resulted from increased feeding and body mass gain by hosts parasitized
      by large broods of wasps. Our results demonstrate phenotypic plasticity in
      resource allocation between growth and reproduction in a developing parasitoid.
      This plasticity may contribute to an adaptive balance between longevity and
      mobility vs. fecundity during the adult stage.

PMID- 29659605
TI  - Chronic kidney disease in the global adult HIV-infected population: A systematic
      review and meta-analysis.
AB  - INTRODUCTION: The widespread use of antiretroviral therapies (ART) has increased
      life expectancy in HIV patients, predisposing them to chronic non-communicable
      diseases including Chronic Kidney Disease (CKD). We performed a systematic review
      and meta-analysis (PROSPERO registration number CRD42016036246) to determine the
      global and regional prevalence of CKD in HIV patients. METHODS: We searched
      PubMed, Web of Science, EBSCO and AJOL for articles published between January
      1982 and May 2016. CKD was defined as estimated glomerular filtration rate (eGFR)
      <60ml/min using the MDRD, Cockcroft-Gault or CKD-EPI equations. Random effects
      model was used to combine prevalence estimates from across studies after variance
      stabilization via Freeman-Tukey transformation. RESULT: Sixty-one eligible
      articles (n = 209,078 HIV patients) in 60 countries were selected. The overall
      CKD prevalence was 6.4% (95%CI 5.2-7.7%) with MDRD, 4.8% (95%CI 2.9-7.1%) with
      CKD-EPI and 12.3% (95%CI 8.4-16.7%) with Cockcroft-Gault; p = 0.003 for
      difference across estimators. Sub-group analysis identified differences in
      prevalence by WHO region with Africa having the highest MDRD-based prevalence at
      7.9% (95%CI 5.2-11.1%). Within Africa, the pooled MDRD-based prevalence was
      highest in West Africa [14.6% (95%CI 9.9-20.0%)] and lowest in Southern Africa
      (3.2%, 95%CI 3.0-3.4%). The heterogeneity observed could be explained by WHO
      region, comorbid hypertension and diabetes mellitus, but not by gender, hepatitis
      B or C coinfection, CD4 count or antiretroviral status. CONCLUSION: CKD is common
      in HIV-infected people, particularly in Africa. HIV treatment programs need to
      intensify screening for CKD with added need to introduce global guidelines for
      CKD identification and treatment in HIV positive patients.

PMID- 29659608
TI  - Clinical impact of endometrial cancer stratified by genetic mutational profiles,
      POLE mutation, and microsatellite instability.
AB  - BACKGROUND: The molecular characterization of endometrial cancer (EC) can
      facilitate identification of various tumor subtypes. Although EC patients with
      POLE mutations reproducibly demonstrate better prognosis, the outcome of patients
      with microsatellite instability (MSI) remains controversial. This study attempted
      to interrogate whether genetic stratification of EC can identify distinct subsets
      with prognostic significance. MATERIALS AND METHODS: A cohort of 138 EC patients
      who underwent surgical resection with curative intent was enrolled. Sanger
      sequencing was used to evaluate mutations in the POLE and KRAS genes. MSI
      analysis was performed using four mononucleotide repeat markers and methylation
      status of the MLH1 promoter was measured by a fluorescent bisulfite polymerase
      chain reaction (PCR). Protein expression for mismatch repair (MMR) proteins was
      evaluated by immunohistochemistry (IHC). RESULTS: Extensive hypermethylation of
      the MLH1 promoter was observed in 69.6% ECs with MLH1 deficiency and 3.5% with
      MMR proficiency, but in none of the ECs with loss of other MMR genes (P < .0001).
      MSI-positive and POLE mutations were found in 29.0% and 8.7% EC patients,
      respectively. Our MSI analysis showed a sensitivity of 92.7% for EC patients with
      MMR deficiency, and a specificity of 97.9% for EC patients with MMR proficiency.
      In univariate and multivariate analyses, POLE mutations and MSI status was
      significantly associated with progression-free survival (P = 0.0129 and 0.0064,
      respectively) but not with endometrial cancer-specific survival. CONCLUSIONS:
      This study provides significant evidence that analyses of proofreading POLE
      mutations and MSI status based on mononucleotide repeat markers are potentially
      useful biomarkers to identify EC patients with better prognosis.

PMID- 29659609
TI  - Patients' perceived needs of osteoarthritis health information: A systematic
      scoping review.
AB  - BACKGROUND: Optimal management of osteoarthritis requires active patient
      participation. Understanding patients' perceived health information needs is
      important in order to optimize health service delivery and health outcomes in
      osteoarthritis. We aimed to review the existing literature regarding patients'
      perceived health information needs for OA. METHODS: A systematic scoping review
      was performed of publications in MEDLINE, EMBASE, CINAHL and PsycINFO (1990
      2016). Descriptive data regarding study design and methodology were extracted and
      risk of bias assessed. Aggregates of patients' perceived needs of osteoarthritis
      health information were categorized. RESULTS: 30 studies from 2876 were included:
      16 qualitative, 11 quantitative and 3 mixed-methods studies. Three areas of
      perceived need emerged: (1) Need for clear communication: terms used were
      misunderstood or had unintended connotations. Patients wanted clear explanations.
      (2) Need for information from various sources: patients wanted accessible health
      professionals with specialist knowledge of arthritis. The Internet, whilst a
      source of information, was acknowledged to have dubious reliability. Print media,
      television, support groups, family and friends were utilised to fulfil diverse
      information needs. (3) Needs of information content: patients desired more
      information about diagnosis, prognosis, management and prevention. CONCLUSIONS:
      Patients desire more information regarding the diagnosis of osteoarthritis, its
      impact on daily life and its long-term prognosis. They want more information not
      only about pharmacological management options, but also non-pharmacological
      options to help them manage their symptoms. Also, patients wanted this
      information to be delivered in a clear manner from multiple sources of health
      information. To address these gaps, more effective communication strategies are
      required. The use of a variety of sources and modes of delivery may enable the
      provision of complementary material to provide information more successfully,
      resulting in better patient adherence to guidelines and improved health outcomes.

PMID- 29659610
TI  - DNA metabarcoding and microscopic analyses of sea turtles biofilms: Complementary
      to understand turtle behavior.
AB  - Sea turtles are distributed in tropical and subtropical seas worldwide. They play
      several ecological roles and are considered important indicators of the health of
      marine ecosystems. Studying epibiotic diatoms living on turtle shells
      suggestively has great potential in the study of turtle behavior because diatoms
      are always there. However, diatom identification at the species level is time
      consuming, requires well-trained specialists, and there is a high probability of
      finding new taxa growing on turtle shells, which makes identification tricky. An
      alternative approach based on DNA barcoding and high throughput sequencing (HTS),
      metabarcoding, has been developed in recent years to identify species at the
      community level by using a DNA reference library. The suitabilities of
      morphological and molecular approaches were compared. Diatom assemblages were
      sampled from seven juvenile green turtles (Chelonia mydas) from Mayotte Island,
      France. The structures of the epibiotic diatom assemblages differed between both
      approaches. This resulted in different clustering of the turtles based on their
      diatom communities. Metabarcoding allowed better discrimination between turtles
      based on their epibiotic diatom assemblages and put into evidence the presence of
      a cryptic diatom diversity. Microscopy, for its part, provided more ecological
      information of sea turtles based on historical bibliographical data and the
      abundances of ecological guilds of the diatom species present in the samples.
      This study shows the complementary nature of these two methods for studying
      turtle behavior.

PMID- 29659611
TI  - Preoperative evaluation of the efficacy of radio-hyperthermo-chemotherapy for
      soft tissue sarcoma in a case series.
AB  - PURPOSE: Radio-hyperthermo-chemo (RHC) therapy, which combines radiotherapy,
      hyperthermia, and chemotherapy, for malignant soft tissue tumors has been
      introduced with the aim of decreasing the possibility of local recurrence after
      surgery. To avoid unnecessary neoadjuvant therapy and to plan the appropriate
      surgical treatment, surveillance of RHC therapeutic efficacy during treatment is
      necessary. In this study, we determined the optimal response criteria to evaluate
      the efficacy of RHC by comparing preoperative images before and after RHC with
      pathological evaluation of necrosis in the resected tumor. PATIENTS AND METHODS:
      From 2004 to 2014, 20 patients were enrolled into this study. Needle biopsy
      revealed 6 cases of myxoid liposarcoma, 6 cases of undifferentiated pleomorphic
      sarcoma, 4 cases of myxofibrosarcoma, and 4 cases of synovial sarcoma. Based on
      the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or modified RECIST,
      we calculated the responses to RHC therapy by comparing pre- and post-RHC therapy
      images. In addition, resected specimens underwent pathological analysis to
      evaluate response based on tumor necrosis. The correlation between assessment
      based on preoperative images and resected tumors were evaluated by the Spearman's
      rank-order correlation coefficient. RESULT: From the surgical specimens,
      pathological assessment of necrosis in resected tumor were assessed as less than
      50% (2 cases), 50-90% (9 cases), 90-99% (6 cases), and total necrosis (3 cases).
      Use of the RECIST 1.1 underestimated good responders as stable disease (SD) or
      progressive disease (PD) in 5 out of 15 cases; on the other hand, use of the
      modified RECIST did not underestimate the pathological assessment of necrosis.
      The correlations between responses based on preoperative images and those based
      on histological assessments were 0.23 (RECIST 1.1) and 0.76 (modified RECIST).
      CONCLUSION: Because pathological responses can be underestimated using the RECIST
      1.1, the modified RECIST, which take into consideration tumor viability, as
      assessed by contrast MRI, should also be considered when evaluating the efficacy
      of RHC.

PMID- 29659612
TI  - Effects of shortened scanning intervals on calculated regional rates of cerebral
      protein synthesis determined with the L-[1-11C]leucine PET method.
AB  - To examine effects of scan duration on estimates of regional rates of cerebral
      protein synthesis (rCPS), we reanalyzed data from thirty-nine previously reported
      L-[1-11C]leucine PET studies. Subjects consisted of 12 healthy volunteers studied
      twice, awake and under propofol sedation, and 15 subjects with fragile X syndrome
      (FXS) studied once under propofol sedation. All scans were acquired on a high
      resolution scanner. We used a basis function method for voxelwise estimation of
      parameters of the kinetic model of L-[1-11C]leucine and rCPS over the interval
      beginning at the time of tracer injection and ending 30, 45, 60, 75 or 90 min
      later. For each study and scan interval, regional estimates in nine regions and
      whole brain were obtained by averaging voxelwise estimates over all voxels in the
      region. In all three groups rCPS was only slightly affected by scan interval
      length and was very stable between 60 and 90 min. Furthermore, statistical
      comparisons of rCPS between awake and sedated healthy volunteers provided almost
      identical results when they were based on 60 min scan data as when they were
      based on data from the full 90 min interval. Statistical comparisons between
      sedated healthy volunteers and sedated subjects with FXS also yielded almost
      identical results when based on 60 and 90 min scan intervals. We conclude that,
      under the conditions of our studies, scan duration can be shortened to 60 min
      without loss of precision.

PMID- 29659613
TI  - Diagnostic delay and mortality of active tuberculosis in patients after kidney
      transplantation in a tertiary care hospital in China.
AB  - TB infection in patients after kidney transplantation remains a concern in a
      successful long-term outcome. This retrospective, descriptive study was performed
      on tuberculosis infection after kidney transplantation in the Department of
      Infectious Disease of the First Affiliated Hospital of Zhejiang University, a
      tertiary care hospital in China, from January 2011 to April 2017, with the aim to
      explain the clinical features of active tuberculosis after kidney transplantation
      and explore the correlated factors for diagnostic delay and mortality. It
      included 48 cases. All these cases were followed up for at least 12 months after
      anti-tuberculosis therapy, except the ones who died during this period. The
      median time of transplantation to active tuberculosis of these 48 patients was
      about 5.4 years. The time from a first hospital visit to the diagnosis
      (diagnostic delay) of 12 (25%) cases was more than 30 days. The correlated
      factors for the diagnostic delay more than 30 days were a fever for more than 2
      weeks and antibiotic use for more than 2 weeks. Nine (18.8%) cases died during
      the anti-tuberculosis therapy or following-up period due to TB relapse. The risk
      factors for mortality were severe complications, such as encephaledema, severe
      pneumonia, intestinal perforation, liver function failure, and the following
      multiple-organ failure. In conclusion, the possibility of tuberculosis infection
      should be carefully assessed and sometimes diagnostic anti-tuberculosis therapy
      may be required for patients who had a fever for more than 2 weeks or used
      antibiotics for more than 2 weeks after kidney transplantation. Severe
      complications and the following multiple-organ failure might increase the
      mortality among these patients.

PMID- 29659614
TI  - KSHV induces immunoglobulin rearrangements in mature B lymphocytes.
AB  - Kaposi sarcoma herpesvirus (KSHV/HHV-8) is a B cell tropic human pathogen, which
      is present in vivo in monotypic immunoglobulin lambda (Iglambda) light chain but
      polyclonal B cells. In the current study, we use cell sorting to infect specific
      B cell lineages from human tonsil specimens in order to examine the
      immunophenotypic alterations associated with KSHV infection. We describe IL-6
      dependent maturation of naive B lymphocytes in response to KSHV infection and
      determine that the Iglambda monotypic bias of KSHV infection in vivo is due to
      viral induction of BCR revision. Infection of immunoglobulin kappa (Igkappa)
      naive B cells induces expression of Iglambda and isotypic inclusion, with
      eventual loss of Igkappa. We show that this phenotypic shift occurs via re
      induction of Rag-mediated V(D)J recombination. These data explain the selective
      presence of KSHV in Iglambda B cells in vivo and provide the first evidence that
      a human pathogen can manipulate the molecular mechanisms responsible for
      immunoglobulin diversity.

PMID- 29659615
TI  - Natural regeneration on seismic lines influences movement behaviour of wolves and
      grizzly bears.
AB  - Across the boreal forest of Canada, habitat disturbance is the ultimate cause of
      caribou (Rangifer tarandus caribou) declines. Habitat restoration is a focus of
      caribou recovery efforts, with a goal to finding ways to reduce predator use of
      disturbances, and caribou-predator encounters. One of the most pervasive
      disturbances within caribou ranges in Alberta, Canada are seismic lines cleared
      for energy exploration. Seismic lines facilitate predator movement, and although
      vegetation on some seismic lines is regenerating, it remains unknown whether
      vegetation regrowth is sufficient to alter predator response. We used Light
      Detection and Ranging (LiDAR) data, and GPS locations, to understand how
      vegetation and other attributes of seismic lines influence movements of two
      predators, wolves (Canis lupus) and grizzly bears (Ursus arctos). During winter,
      wolves moved towards seismic lines regardless of vegetation height, while during
      spring wolves moved towards seismic lines with higher vegetation. During summer,
      wolves moved towards seismic lines with lower vegetation and also moved faster
      near seismic lines with vegetation <0.7 m. Seismic lines with lower vegetation
      height were preferred by grizzly bears during spring and summer, but there was no
      relationship between vegetation height and grizzly bear movement rates. These
      results suggest that wolves use seismic lines for travel during summer, but
      during winter wolf movements relative to seismic lines could be influenced by
      factors additional to movement efficiency; potentially enhanced access to areas
      frequented by ungulate prey. Grizzly bears may be using seismic lines for
      movement, but could also be using seismic lines as a source of vegetative food or
      ungulate prey. To reduce wolf movement rate, restoration could focus on seismic
      lines with vegetation <1 m in height. However our results revealed that seismic
      lines continue to influence wolf movement behaviour decades after they were
      built, and even at later stages of regeneration. Therefore it remains unknown at
      what stage of natural regeneration, if any, wolves cease to respond to seismic
      lines. To reduce wolf response to seismic lines, active restoration tactics like
      blocking seismic lines and tree planting, along with management of alternate
      prey, could be evaluated.

PMID- 29659616
TI  - Estimating nearshore coral reef-associated fisheries production from the main
      Hawaiian Islands.
AB  - Currently, information on nearshore reef-associated fisheries is frequently
      disparate or incomplete, creating a challenge for effective management. This
      study utilized an existing non-commercial fishery dataset from Hawai'i, covering
      the period 2004-13, to estimate a variety of fundamental fishery parameters,
      including participation, effort, gear use, and catch per unit effort. We then
      used those data to reconstruct total catches per island. Non-commercial fisheries
      in this case comprise recreational, subsistence, and cultural harvest, which may
      be exchanged, but are not sold. By combining those data with reported commercial
      catch data, we estimated annual catch of nearshore reef-associated fisheries in
      the main Hawaiian Islands over the study period to be 1,167,758 +/- 43,059 kg
      year-1 (mean +/- standard error). Average annual commercial reef fish catch over
      the same time period-184,911 kg year-1-was 16% of the total catch, but that
      proportion varied greatly among islands, ranging from 23% on O'ahu to 5% on
      Moloka'i. These results emphasize the importance of reef fishing in Hawai'i for
      reasons beyond commerce, such as food security and cultural practice, and
      highlight the large differences in fishing practices across the Hawaiian Islands.

PMID- 29659617
TI  - Resistance and resilience of small-scale recirculating aquaculture systems (RAS)
      with or without algae to pH perturbation.
AB  - The experimental set-up of this study mimicked recirculating aquaculture systems
      (RAS) where water quality parameters such as dissolved oxygen, pH, temperature,
      and turbidity were controlled and wastes produced by fish and feeding were
      converted to inorganic forms. A key process in the RAS was the conversion of
      ammonia to nitrite and nitrite to nitrate through nitrification. It was
      hypothesized that algae inclusion in RAS would improve the ammonia removal from
      the water; thereby improving RAS water quality and stability. To test this
      hypothesis, the stability of the microbiota community composition in a freshwater
      RAS with (RAS+A) or without algae (RAS-A) was challenged by introducing an acute
      pH drop (from pH 7 to 4 during three hours) to the system. Stigeoclonium nanum, a
      periphytic freshwater microalga was used in this study. No significant effect of
      the algae presence was found on the resistance to the acute pH drop on ammonia
      conversion to nitrite and nitrite conversion to nitrate. Also the resilience of
      the ammonia conversion to the pH drop disruption was not affected by the addition
      of algae. This could be due to the low biomass of algae achieved in the RAS.
      However, with regard to the conversion step of nitrite to nitrate, RAS+A was
      significantly more resilient than RAS-A. In terms of overall bacterial
      communities, the composition and predictive function of the bacterial communities
      was significantly different between RAS+A and RAS-A.

PMID- 29659618
TI  - Vitamin D receptor suppresses proliferation and metastasis in renal cell
      carcinoma cell lines via regulating the expression of the epithelial Ca2+ channel
      TRPV5.
AB  - We previously demonstrated that transient receptor potential vanilloid subfamily
      5 (TRPV5) expression was decreased in renal cell carcinoma (RCC) compared with
      that in normal kidney tissues, a finding that was correlated with vitamin D
      receptor (VDR) expression, but further investigations is warranted. The aim of
      this study was to elucidate whether VDR could regulate the expression of TRPV5
      and affect proliferation and metastasis in RCC. In this study, we used lentivirus
      to conduct the model of VDR overexpression and knockdown caki-1 and 786-O RCC
      cell lines in vitro. The results demonstrated that VDR overexpression
      significantly inhibited RCC cells proliferation, migration and invasion, and
      promoted apoptosis by the MTT, transwell cell migration/invasion and flow
      cytometry assays, respectively. However, VDR knockdown in RCC cells had the
      opposite effect. The RNA-sequence assay, which was assessed in caki-1 cells after
      VDR overexpression and knockdown, also indicated that significantly
      differentially expressed genes were associated with cell apoptotic,
      differentiation, proliferation and migration. RT-PCR and western blot analysis
      showed that VDR knockdown increased TRPV5 expression and VDR overexpression
      decreased TRPV5 expression in caki-1 cells. Furthermore, knockdown of TRPV5
      expression suppressed the VDR knockdown-induced change in the proliferation,
      migration and invasion in caki-1 cells. Taken together, these findings confirmed
      that VDR functions as a tumour suppressor in RCC cells and suppresses the
      proliferation, migration and invasion of RCC through regulating the expression of
      TRPV5.

PMID- 29659619
TI  - Characterisation of two Toxoplasma PROPPINs homologous to Atg18/WIPI suggests
      they have evolved distinct specialised functions.
AB  - Toxoplasma gondii is a parasitic protist possessing a limited set of proteins
      involved in the autophagy pathway, a self-degradative machinery for protein and
      organelle recycling. This distant eukaryote has even repurposed part of this
      machinery, centered on protein ATG8, for a non-degradative function related to
      the maintenance of the apicoplast, a parasite-specific organelle. However, some
      evidence also suggest Toxoplasma is able to generate autophagic vesicles upon
      stress, and that some autophagy-related proteins, such as ATG9, might be involved
      solely in the canonical autophagy function. Here, we have characterised TgPROP1
      and TgPROP2, two Toxoplasma proteins containing WD-40 repeat that can bind lipids
      for their recruitment to vesicular structures upon stress. They belong to the
      PROPPIN family and are homologues to ATG18/WIPI, which are known to be important
      for the autophagic process. We conducted a functional analysis of these two
      Toxoplasma PROPPINs. One of them is dispensable for normal in vitro growth,
      although it may play a role for parasite survival in specific stress conditions
      or for parasite fitness in the host, through a canonical autophagy-related
      function. The other, however, seems important for parasite viability in normal
      growth conditions and could be primarily involved in a non-canonical function.
      These divergent roles for two proteins from the same family illustrate the
      functional versatility of the autophagy-related machinery in Toxoplasma.

PMID- 29659620
TI  - Why do placentas evolve? Evidence for a morphological advantage during pregnancy
      in live-bearing fish.
AB  - A live-bearing reproductive strategy can induce large morphological changes in
      the mother during pregnancy. The evolution of the placenta in swimming animals
      involves a shift in the timing of maternal provisioning from pre-fertilization
      (females supply their eggs with sufficient yolk reserves prior to fertilization)
      to post-fertilization (females provide all nutrients via a placenta during the
      pregnancy). It has been hypothesised that this shift, associated with the
      evolution of the placenta, should confer a morphological advantage to the females
      leading to a more slender body shape during the early stages of pregnancy. We
      tested this hypothesis by quantifying three-dimensional shape and volume changes
      during pregnancy and in full-grown virgin controls of two species within the live
      bearing fish family Poeciliidae: Poeciliopsis gracilis (non-placental) and
      Poeciliopsis turneri (placental). We show that P. turneri is more slender than P.
      gracilis at the beginning of the interbrood interval and in virgins, and that
      these differences diminish towards the end of pregnancy. This study provides the
      first evidence for an adaptive morphological advantage of the placenta in live
      bearing fish. A similar morphological benefit could drive the evolution of
      placentas in other live-bearing (swimming) animal lineages.

PMID- 29659622
TI  - The association of single and combined factors of sedentary behavior and physical
      activity with subjective cognitive complaints among community-dwelling older
      adults: Cross-sectional study.
AB  - Subjective cognitive complaints (SCC) might be a meaningful indicator of dementia
      onset or mild cognitive impairment, and identifying the related factors of SCC
      could contribute to preventing these diseases. However, the relationship between
      SCC and lifestyle factors remains largely unproven. The purpose of this study was
      to examine the association of type of sedentary behavior, physical activity, or
      their combination with SCC among community-dwelling older adults. In 2016, 6677
      community-living elderly were recruited to participate in a survey investigating
      cognition, physical activity, and sedentary behavior. In total, 5328 participants
      responded to the questionnaire (79.8% valid response rate). SCC was assessed
      using the National Functional Survey Questionnaire (Kihon checklist). The
      relationships between SCC and physical activity, sedentary behavior (reading
      books or newspapers, and television viewing), or combined physical activity and
      sedentary behavior were examined via multiple logistic regression analysis. The
      analysis revealed that moderate-to-vigorous physical activity (>=150 min/week)
      was significantly related with a lower risk of SCC (odds ratio [OR] = 0.85; 95%
      confidence interval [CI] = 0.74-0.97), and that reading behavior showed a dose
      response relationship with SCC (OR for 10-20 min/day = 0.63; 95% CI = 0.53-0.75;
      OR for 20-30 min/day = 0.59; 95% CI = 0.49-0.71; OR for >=30 min/day = 0.47; 95%
      CI = 0.39-0.57). In addition, among those reporting high physical activity and
      >=30 min/day for reading time, the OR for SCC was 0.40 (95% CI = 0.32-0.50)
      compared with the combined group reporting lower physical activity and non
      readers. The present study shows that increased physical activity and reading
      time may be related to a reduced risk for SCC among community-dwelling older
      adults.

PMID- 29659621
TI  - Referral bias in ALS epidemiological studies.
AB  - BACKGROUND: Despite concerns about the representativeness of patients from ALS
      tertiary centers as compared to the ALS general population, the extent of
      referral bias in clinical studies remains largely unknown. Using data from EURALS
      consortium we aimed to assess nature, extent and impact of referral bias.
      METHODS: Four European ALS population-based registries located in Ireland,
      Piedmont, Puglia, Italy, and Limousin, France, covering 50 million person-years,
      participated. Demographic and clinic characteristics of ALS patients diagnosed in
      tertiary referral centers were contrasted with the whole ALS populations enrolled
      in registries in the same geographical areas. RESULTS: Patients referred to ALS
      centers were younger (with difference ranging from 1.1 years to 2.4 years), less
      likely to present a bulbar onset, with a higher proportion of familial
      antecedents and a longer survival (ranging from 11% to 15%) when compared to the
      entire ALS population in the same geographic area. CONCLUSIONS: A trend for
      referral bias is present in cohorts drawn from ALS referral centers. The
      magnitude of the possible referral bias in a particular tertiary center can be
      estimated through a comparison with ALS patients drawn from registry in the same
      geographic area. Studies based on clinical cohorts should be cautiously
      interpreted. The presence of a registry in the same area may improve the complete
      ascertainment in the referral center.

PMID- 29659623
TI  - Loss of CXCR6 coreceptor usage characterizes pathogenic lentiviruses.
AB  - Pandemic HIV-1 originated from the cross-species transmission of SIVcpz, which
      infects chimpanzees, while SIVcpz itself emerged following the cross-species
      transmission and recombination of monkey SIVs, with env contributed by the
      SIVgsn/mus/mon lineage that infects greater spot-nosed, mustached and mona
      monkeys. SIVcpz and HIV-1 are pathogenic in their respective hosts, while the
      phenotype of their SIVgsn/mus/mon ancestors is unknown. However, two well-studied
      SIV infected natural hosts, sooty mangabeys (SMs) and African green monkeys
      (AGMs), typically remain healthy despite high viral loads; these species express
      low levels of the canonical coreceptor CCR5, and recent work shows that CXCR6 is
      a major coreceptor for SIV in these hosts. It is not known what coreceptors were
      used by the precursors of SIVcpz, whether coreceptor use changed during emergence
      of the SIVcpz/HIV-1 lineage, and what T cell subsets express CXCR6 in natural
      hosts. Using species-matched coreceptors and CD4, we show here that SIVcpz uses
      only CCR5 for entry and, like HIV-1, cannot use CXCR6. In contrast, SIVmus
      efficiently uses both CXCR6 and CCR5. Coreceptor selectivity was determined by
      Env, with CXCR6 use abrogated by Pro326 in the V3 crown, which is absent in
      monkey SIVs but highly conserved in SIVcpz/HIV-1. To characterize which cells
      express CXCR6, we generated a novel antibody that recognizes CXCR6 of multiple
      primate species. Testing lymphocytes from SM, the best-studied natural host, we
      found that CXCR6 is restricted to CD4+ effector memory cells, and is expressed by
      a sub-population distinct from those expressing CCR5. Thus, efficient CXCR6 use,
      previously identified in SM and AGM infection, also characterizes a member of the
      SIV lineage that gave rise to SIVcpz/HIV-1. Loss of CXCR6 usage by SIVcpz may
      have altered its cell tropism, shifting virus from CXCR6-expressing cells that
      may support replication without disrupting immune function or homeostasis,
      towards CCR5-expressing cells with pathogenic consequences.

PMID- 29659624
TI  - A 'smart' tube holder enables real-time sample monitoring in a standard lab
      centrifuge.
AB  - The centrifuge is among the oldest and most widely used pieces of laboratory
      equipment, with significant applications that include clinical diagnostics and
      biomedical research. A major limitation of laboratory centrifuges is their "black
      box" nature, limiting sample observation to before and after centrifugation.
      Thus, optimized protocols require significant trial and error, while unoptimized
      protocols waste time by centrifuging longer than necessary or material due to
      incomplete sedimentation. Here, we developed an instrumented centrifuge tube
      receptacle compatible with several commercial benchtop centrifuges that can
      provide real-time sample analysis during centrifugation. We demonstrated the
      system by monitoring cell separations during centrifugation for different spin
      speeds, concentrations, buffers, cell types, and temperatures. We show that the
      collected data are valuable for analytical purposes (e.g. quality control), or as
      feedback to the user or the instrument. For the latter, we verified an adaptation
      where complete sedimentation turned off the centrifuge and notified the user by a
      text message. Our system adds new functionality to existing laboratory
      centrifuges, saving users time and providing useful feedback. This add-on
      potentially enables new analytical applications for an instrument that has
      remained largely unchanged for decades.

PMID- 29659625
TI  - ST waveform analysis for monitoring hypoxic distress in fetal sheep after
      prolonged umbilical cord occlusion.
AB  - INTRODUCTION: The inconclusive clinical results for ST-waveform analysis (STAN)
      in detecting fetal hypoxemia may be caused by the signal processing of the STAN
      device itself. We assessed the performance of a clinical STAN device in signal
      processing and in detecting hypoxemia in a fetal sheep model exposed to prolonged
      umbilical cord occlusion (UCO). METHODS: Eight fetal lambs were exposed to 25
      minutes of UCO. ECG recordings were analyzed during a baseline period and during
      UCO. STAN-event rates and timing of episodic T/QRS rise, baseline T/QRS rise and
      the occurrence of biphasic ST-waveforms, as well as signal loss, were assessed.
      RESULTS: During baseline conditions of normoxemia, a median of 40 (IQR, 25-70)
      STAN-events per minute were detected, compared to 10 (IQR, 2-22) during UCO.
      During UCO STAN-events were detected in five subjects within 10 minutes and in
      six subjects after 18 minutes, respectively. Two subjects did not generate any
      STAN-event during UCO. Biphasic ST event rate was reduced during UCO (median 0,
      IQR 0-5), compared to baseline (median 32, IQR, 6-55). ST-waveforms could not be
      assessed in 62% of the recording time during UCO, despite a good quality of the
      ECG signal. CONCLUSIONS: The STAN device showed limitations in detecting
      hypoxemia in fetal sheep after prolonged UCO. The STAN device produced high false
      positive event rates during baseline and did not detect T/QRS changes adequately
      after prolonged fetal hypoxemia. During 14% of baseline and 62% of the UCO
      period, the STAN-device could not process the ECG signal, despite its good
      quality. Resolving these issues may improve the clinical performance of the STAN
      device.

PMID- 29659626
TI  - Influence of respiratory mechanics and drive on genioglossus movement under
      ultrasound imaging.
AB  - METHODS: Twenty healthy subjects (10 males, age 28+/-5 years [mean +/- SD]) lay
      supine, awake, with the head in a neutral position. Ventilation was monitored
      with inductance bands. Real-time B-mode ultrasound movies were analysed. We
      measured genioglossus motion (i) during spontaneous breathing, voluntary targeted
      breathing (normal tidal volume Vt), and voluntary hyperpnoea (at 1.5Vt and 2 Vt);
      (ii) during inspiratory flow resistive loading; (iii) with changes in end
      expiratory lung volume (EELV). RESULTS: Average peak inspiratory displacement of
      the infero-posterior region of genioglossus was 0.89+/-0.56 mm; 1.02+/-0.88 mm;
      1.27+/-0.70 mm respectively for voluntary Vt, and during voluntary hyperpnoea at
      1.5Vt and 2Vt. A change in genioglossus motion was observed with increased Vt.
      During increasing inspiratory resistive loading, the genioglossus displaced less
      anteriorly (p = 0.005) but more inferiorly (p = 0.027). When lung volume was
      altered, no significant changes in genioglossus movement were observed (p =
      0.115). CONCLUSION: In healthy subjects, we observed non-uniform heterogeneous
      inspiratory motion within the inferoposterior part of genioglossus during
      spontaneous quiet breathing with mean peak displacement between 0.5-2 mm, with
      more displacement in the posterior region than the anterior. This regional
      heterogeneity disappeared during voluntary targeted breathing. This may be due to
      different neural drive to genioglossus during voluntary breathing. During
      inspiratory resistive loading, the observed genioglossus motion may serve to
      maintain upper airway patency by balancing intraluminal negative pressure with
      positive pressure generated by upper airway dilatory muscles. In contrast,
      changes in EELV were not accompanied by major changes in genioglossus motion.

PMID- 29659627
TI  - N6-methyladenosine modification and the YTHDF2 reader protein play cell type
      specific roles in lytic viral gene expression during Kaposi's sarcoma-associated
      herpesvirus infection.
AB  - Methylation at the N6 position of adenosine (m6A) is a highly prevalent and
      reversible modification within eukaryotic mRNAs that has been linked to many
      stages of RNA processing and fate. Recent studies suggest that m6A deposition and
      proteins involved in the m6A pathway play a diverse set of roles in either
      restricting or modulating the lifecycles of select viruses. Here, we report that
      m6A levels are significantly increased in cells infected with the oncogenic human
      DNA virus Kaposi's sarcoma-associated herpesvirus (KSHV). Transcriptome-wide m6A
      sequencing of the KSHV-positive renal carcinoma cell line iSLK.219 during lytic
      reactivation revealed the presence of m6A across multiple kinetic classes of
      viral transcripts, and a concomitant decrease in m6A levels across much of the
      host transcriptome. However, we found that depletion of the m6A machinery had
      differential pro- and anti-viral impacts on viral gene expression depending on
      the cell-type analyzed. In iSLK.219 and iSLK.BAC16 cells the pathway functioned
      in a pro-viral manner, as depletion of the m6A writer METTL3 and the reader
      YTHDF2 significantly impaired virion production. In iSLK.219 cells the defect was
      linked to their roles in the post-transcriptional accumulation of the major viral
      lytic transactivator ORF50, which is m6A modified. In contrast, although the
      ORF50 mRNA was also m6A modified in KSHV infected B cells, ORF50 protein
      expression was instead increased upon depletion of METTL3, or, to a lesser
      extent, YTHDF2. These results highlight that the m6A pathway is centrally
      involved in regulating KSHV gene expression, and underscore how the outcome of
      this dynamically regulated modification can vary significantly between cell
      types.

PMID- 29659629
TI  - Characterization of cocoa production, income diversification and shade tree
      management along a climate gradient in Ghana.
AB  - Reduced climatic suitability due to climate change in cocoa growing regions of
      Ghana is expected in the coming decades. This threatens farmers' livelihood and
      the cocoa sector. Climate change adaptation requires an improved understanding of
      existing cocoa production systems and farmers' coping strategies. This study
      characterized current cocoa production, income diversification and shade tree
      management along a climate gradient within the cocoa belt of Ghana. The
      objectives were to 1) compare existing production and income diversification
      between dry, mid and wet climatic regions, and 2) identify shade trees in cocoa
      agroforestry systems and their distribution along the climatic gradient. Our
      results showed that current mean cocoa yield level of 288kg ha-1yr-1 in the dry
      region was significantly lower than in the mid and wet regions with mean yields
      of 712 and 849 kg ha-1 yr-1, respectively. In the dry region, farmers diversified
      their income sources with non-cocoa crops and off-farm activities while farmers
      at the mid and wet regions mainly depended on cocoa (over 80% of annual income).
      Two shade systems classified as medium and low shade cocoa agroforestry systems
      were identified across the studied regions. The medium shade system was more
      abundant in the dry region and associated to adaptation to marginal climatic
      conditions. The low shade system showed significantly higher yield in the wet
      region but no difference was observed between the mid and dry regions. This study
      highlights the need for optimum shade level recommendation to be climatic region
      specific.

PMID- 29659628
TI  - Interactions between genetic variation and cellular environment in skeletal
      muscle gene expression.
AB  - From whole organisms to individual cells, responses to environmental conditions
      are influenced by genetic makeup, where the effect of genetic variation on a
      trait depends on the environmental context. RNA-sequencing quantifies gene
      expression as a molecular trait, and is capable of capturing both genetic and
      environmental effects. In this study, we explore opportunities of using allele
      specific expression (ASE) to discover cis-acting genotype-environment
      interactions (GxE)-genetic effects on gene expression that depend on an
      environmental condition. Treating 17 common, clinical traits as approximations of
      the cellular environment of 267 skeletal muscle biopsies, we identify 10
      candidate environmental response expression quantitative trait loci (reQTLs)
      across 6 traits (12 unique gene-environment trait pairs; 10% FDR per trait)
      including sex, systolic blood pressure, and low-density lipoprotein cholesterol.
      Although using ASE is in principle a promising approach to detect GxE effects,
      replication of such signals can be challenging as validation requires
      harmonization of environmental traits across cohorts and a sufficient sampling of
      heterozygotes for a transcribed SNP. Comprehensive discovery and replication will
      require large human transcriptome datasets, or the integration of multiple
      transcribed SNPs, coupled with standardized clinical phenotyping.

PMID- 29659630
TI  - Body Mass Index of 92,027 patients acutely admitted to general hospitals in
      Denmark: Associated clinical characteristics and 30-day mortality.
AB  - BACKGROUND: Data are sparse on the range of BMI among patients acutely admitted
      to general hospitals. We investigated BMI values and associated patient
      characteristics, reasons for hospital admission, and mortality in Denmark.
      METHODS: We identified all persons with an acute inpatient admission 2011-2014 in
      Central Denmark Region and assessed BMI measurements recorded in the Clinical
      Information System. We used cross-sectional and cohort analyses to examine the
      BMI distribution and its association with demographic characteristics,
      comorbidities, medication use, tobacco smoking, reasons for admission, and 30-day
      mortality. RESULTS: Among 92,027 acutely admitted patients (median age 62 years,
      49% female) with a BMI measurement, 4% had a BMI (kg/m2) <18.5, 42% a BMI between
      18.5 and 25, 34% a BMI between 25 and 30, and 20% a BMI >=30. Compared with
      normal-weight patients, 30-day mortality was high among patients with BMI <18.5
      (7.5% vs. 2.8%, age- and smoking-adjusted odds ratio (aOR) 2.4; 95% confidence
      interval (CI): 2.0-2.9, whereas patients with overweight (aOR 0.7; 95% CI: 0.6
      0.8) and obesity class I (aOR 0.8; 95% CI: 0.6-0.9)). Compared with the total
      population, patients with BMI <18.5 were older (68 years median); more were
      female (73%); more had comorbidities (Charlson Comorbidity Index score >0 in 42%
      vs. 33% overall), more were current smokers (45% vs. 27% overall), and acute
      admissions due to respiratory diseases or femoral fractures were frequent. In
      contrast, patients with BMI >=30 were relatively young (59 years median), fewer
      smoked (24%): type 2 diabetes, sleep disorders, cholelithiasis, and heart failure
      were frequent diagnoses. Prevalence of therapies for metabolic syndrome, pain,
      and psychiatric disorders increased with higher BMI, while patients with BMI
      <18.5 frequently used asthma medications, glucocorticoids, and antibiotics.
      CONCLUSION: In patients acutely admitted to general hospitals, reasons for
      hospital admission and associated clinical characteristics differ substantially
      according to BMI range. BMI <18.5 is a clinical predictor of high short-term
      mortality.

PMID- 29659631
TI  - The hemodynamic effects of intravenous paracetamol (acetaminophen) vs normal
      saline in cardiac surgery patients: A single center placebo controlled randomized
      study.
AB  - The hemodynamic effects of intravenous (IV) paracetamol in patients undergoing
      cardiac surgery are unknown. We performed a prospective single center placebo
      controlled randomized study with parallel group design in adult patients
      undergoing elective cardiac surgery. Participants received paracetamol (1 gram)
      IV or placebo (an equal volume of 0.9% saline) preoperatively followed by two
      postoperative doses 6 hours apart. The primary endpoint was the absolute change
      in systolic (SBP) 30 minutes after the preoperative infusion, analysed using an
      ANCOVA model. Secondary endpoints included absolute changes in mean arterial
      pressure (MAP) and diastolic blood pressure (DPB), and other key hemodynamic
      variables after each infusion. All other endpoints were analysed using random
      effect generalized least squares regression modelling with individual patients
      treated as random effects. Fifty participants were randomly assigned to receive
      paracetamol (n = 25) or placebo (n = 25). Post preoperative infusion, paracetamol
      decreased SBP by a mean (SD) of 13 (18) mmHg, p = 0.02, compared to a mean (SD)
      of 1 (11) mmHg with saline. Paracetamol decreased MAP and DBP by a mean (SD) of 9
      (12) mmHg and 8 (9) mmHg (p = 0.01 and 0.02), respectively, compared to a mean
      (SD) of 1 (8) mmHg and 0 (6) mmHg with placebo. Postoperatively, there were no
      significant differences in pressure or flow based hemodynamic parameters in both
      groups. This study provides high quality evidence that the administration of IV
      paracetamol in patients undergoing cardiac surgery causes a transient decrease in
      preoperative blood pressure when administered before surgery but no adverse
      hemodynamic effects when administered in the postoperative setting.

PMID- 29659632
TI  - Correction: Enterohemorrhagic Escherichia coli O157 subclade 8b strains in Chiba
      Prefecture, Japan, produced larger amounts of Shiga toxin 2 than strains in
      subclade 8a and other clades.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0191834.].

PMID- 29659633
TI  - Correction: Transporter genes identified in landraces associated with high zinc
      in polished rice through panicle transcriptome for biofortification.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0192362.].

PMID- 29659635
TI  - Correction: Psychometric properties of the Resilience Scale for Adults (RSA) and
      its relationship with life-stress, anxiety and depression in a Hispanic Latin
      American community sample.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0187954.].

PMID- 29659634
TI  - Genome-wide analysis of basic helix-loop-helix superfamily members in peach.
AB  - The basic helix-loop-helix (bHLH) transcription factor family is a superfamily
      found in all eukaryotes that plays important roles in regulating growth and
      development. Over the past several decades, many bHLH superfamily genes have been
      identified and characterized in herbaceous and woody plants. However, the genes
      belonging to the bHLH superfamily in peach (Prunus persica) have not yet been
      comprehensively identified and characterized. Here, we identified 95 members of
      the bHLH superfamily in the peach genome, and these genes were classified into 19
      subfamilies based on a phylogenetic comparison with bHLH proteins from
      Arabidopsis. The members within each subfamily were highly conserved according to
      the analysis of motif compositions and exon/intron organizations. The 95 bHLH
      genes were unevenly distributed on chromosomes 1 to 8 of the peach genome. We
      identified 57 pairs of bHLH members that were orthologous between peach and
      Arabidopsis. Additionally, 48 pairs of paralogous bHLH genes were identified on
      the eight chromosomes of the peach genome. Coupled with relative expression
      analysis of bHLH genes in red-fleshed peach fruit at five developmental stages,
      we identified several bHLH genes that might be involved in fruit development and
      anthocyanin biosynthesis. This study provides insight into the molecular
      mechanisms through which these genes are involved in the regulation of biological
      and biochemical processes in peach and lays the foundation for further studies on
      these genes.

PMID- 29659637
TI  - [Restoration of pathological tooth wear].
AB  - On account of tooth wear, a 30-year-old man and a 23-year-old woman were referred
      to a clinic for specialised dental services by their general dentist. The man
      suffered from degradation of hard dental tissues. He was not in pain but had some
      functional problems. In addition, the diminishing aesthetics bothered him. The
      woman suffered from pain frequently, had mild functional complaints and a deep
      bite. Treatment of pathological tooth wear begins with a sound diagnosis and
      investigating and eliminating aetiological factors. Sufficient motivation on the
      patient's side is also important. The treatment should be as minimally invasive
      as possible. When indirect restorations are absent a dynamic treatment plan would
      be preferred, in which new spatial relations can be tested in composites. For the
      treatment of localised loss of dental tissue the Dahl Concept might be
      considered. Both cases emphasise the importance of evaluating the implemented
      treatment. Long-term follow-up is necessary for the enhancement of knowledge and
      experience in the interpretation of the aetiology of and approach to severe tooth
      wear.

PMID- 29659636
TI  - Prognostic score to predict mortality during TB treatment in TB/HIV co-infected
      patients.
AB  - BACKGROUND: Estimating mortality risk during TB treatment in HIV co-infected
      patients is challenging for health professionals, especially in a low TB
      prevalence population, due to the lack of a standardized prognostic system. The
      current study aimed to develop and validate a simple mortality prognostic scoring
      system for TB/HIV co-infected patients. METHODS: Using data from the CDC's
      Tuberculosis Genotyping Information Management System of TB patients in Texas
      reported from 01/2010 through 12/2016, age >=15 years, HIV(+), and outcome being
      "completed" or "died", we developed and internally validated a mortality
      prognostic score using multiple logistic regression. Model discrimination was
      determined by the area under the receiver operating characteristic (ROC) curve
      (AUC). The model's good calibration was determined by a non-significant Hosmer
      Lemeshow's goodness of fit test. RESULTS: Among the 450 patients included in the
      analysis, 57 (12.7%) died during TB treatment. The final prognostic score used
      six characteristics (age, residence in long-term care facility, meningeal TB,
      chest x-ray, culture positive, and culture not converted/unknown), which are
      routinely collected by TB programs. Prognostic scores were categorized into three
      groups that predicted mortality: low-risk (<20 points), medium-risk (20-25
      points) and high-risk (>25 points). The model had good discrimination and
      calibration (AUC = 0.82; 0.80 in bootstrap validation), and a non-significant
      Hosmer-Lemeshow test p = 0.71. CONCLUSION: Our simple validated mortality
      prognostic scoring system can be a practical tool for health professionals in
      identifying TB/HIV co-infected patients with high mortality risk.

PMID- 29659638
TI  - [The prevalence of tooth wear in the Dutch adult population].
AB  - This study, performed in 2013, aimed to assess the prevalence of tooth wear in
      the Dutch adult population. The prevalence of tooth wear was not only determined
      for different age groups but also according to gender, socioeconomic status and
      types of teeth. Results were compared with the outcomes of a previous study in a
      comparable population in 2007. The data were collected as part of a comprehensive
      dental-epidemiological research project. The 1,125 adults from the city of 's
      Hertogenbosch who participated in the project were subdivided into 5 age groups.
      Tooth wear was quantified using a 5-point ordinal occlusal/incisal grading scale.
      The number of teeth affected by tooth wear was higher in older age groups. Men
      showed more tooth wear than women, as did individuals with lower socioeconomic
      status, among whom a similar tendency was observed. Tooth wear prevalence found
      in 2013 was higher in all age groups than in 2007. One can conclude that tooth
      wear is a common condition in the Dutch adult population.

PMID- 29659639
TI  - [Preventive dentistry 10. Erosive tooth wear].
AB  - Erosive tooth wear has recently been at the centre of attention and its
      prevalence of erosive tooth wear among adolescents in the Netherlands appears to
      be rising. The multifactorial nature of the aetiology of the condition makes it
      difficult to identify the relevant causal factors, both in individual cases and
      within the general population. Preventive intervention is indicated in those
      cases where (active) erosive tooth wear is diagnosed. Early diagnosis is
      important, especially in younger patients. Preventive measures, such as dietary
      advice and the use of fluoride, are recommended but the scientific evidence for
      their effectiveness is still limited. In cases where acid reflux disease is the
      cause, treatment with medicines can have the effect of reducing the progression
      of tooth wear. Recognising a non-active condition, for example after successful
      preventive treatment, is difficult, but will be supported with digital methods in
      the near future.

PMID- 29659640
TI  - [European statement of consensus regarding the treatment of severe tooth wear].
AB  - In 2016, a European consensus meeting was held regarding the treatment of severe
      tooth wear. This meeting resulted in the publication of the European statement of
      consensus on the treatment of severe tooth wear in 2017. In the statement, new
      definitions of physiological and pathological tooth wear are described,
      recommendations for diagnosis and taking preventive measure are presented, and
      advice for counseling and monitoring is offered to better elucidate the
      underlying aetiological factors causing tooth wear in the patient. The decision
      whether restorative treatment is appropriate is multifactorial and partially
      dependent on the severity and the consequences of the wear and on the aesthetic
      and functional wishes of the patient. Restorative intervention should be delayed
      as long as possible, but when such intervention is indicated, the preference is
      for minimally invasive techniques using direct, indirect or hybrid treatment
      methods.

PMID- 29659641
TI  - Introduction.

PMID- 29659642
TI  - The Disease Burden of Atopic Dermatitis.
AB  - Recent studies have shed light on the nature of the burden of atopic dermatitis.
      Analysis of observational data has revealed the effect of atopic dermatitis in
      diverse areas such as work productivity, physical activity, mood, and risk of
      comorbidities beyond other atopic conditions. Studies on adults with moderate to
      severe disease show that the symptoms and consequences of atopic dermatitis
      affect many aspects of their lives. A clearer understanding of the burden for
      patients can inform open, sensitive discussions about goals of therapy. Semin
      Cutan Med Surg 36(supp4):S92-S94.

PMID- 29659643
TI  - Food Allergy and Atopic Dermatitis: Fellow Travelers or Triggers?
AB  - Many children with atopic dermatitis also have an allergy to one or more foods,
      but the presence of these two conditions in an individual does not necessarily
      indicate a causal link between them. Testing and interpretation, sometimes with
      specialist consultation, may be required to discern whether food allergy is
      present in a child with atopic dermatitis and-if it is present-whether the food
      is triggering or exacerbating signs and symptoms of atopic dermatitis. Recent
      milestone trials have demonstrated that early introduction of peanuts can reduce
      the development of peanut allergy in at-risk children. Parents may benefit from
      education about current revised guidelines that now recommend offering peanut
      containing foods to most children at the time he or she is ready for solid food.
      Semin Cutan Med Surg 36(supp4):S95-S97.

PMID- 29659644
TI  - Topical Therapy for Atopic Dermatitis: New and Investigational Agents.
AB  - Recently a new class of topical medications for mild to moderate atopic
      dermatitis has been introduced with US Food and Drug Administration (FDA)
      approval of the first new prescription medication for this condition in more than
      a decade. Crisaborole, the newly approved medication, has relieved pruritus in
      more than one-third of patients within as little as 48 hours. It also has
      demonstrated efficacy in patients with skin of color. Topical therapies
      representing other new approaches to atopic dermatitis, with novel mechanisms of
      action, have shown promise in clinical development. Semin Cutan Med Surg
      36(supp4):S99-S102.

PMID- 29659645
TI  - Systemic Therapy of Atopic Dermatitis: Welcome to the Revolution.
AB  - Until recently, systemic therapy of atopic dermatitis was limited to off-label
      use of immunomodulators, which can pose significant safety concerns, and
      treatment with systemic corticosteroids, not recommended in the most recent
      guidelines. The introduction of dupilumab in 2017 marked a major advance in
      systemic therapy for atopic dermatitis. It has demonstrated long-term efficacy in
      adults with moderate to severe disease, and is being studied in children. Several
      other biologic agents and "small molecules" with varying mechanisms of action are
      in phase 2 or 3 development. Semin Cutan Med Surg 36(supp4):S103-S105.

PMID- 29659646
TI  - Improving Outcomes Through Therapeutic Patient Education.
AB  - Therapeutic patient education is a nascent movement in the care of atopic
      dermatitis, offering patients-and, for children, their caregivers-knowledge,
      skills, support, and coping strategies for managing what for many is a relapsing/
      remitting chronic disease that severely compromises quality of life.
      Interventions range from a written treatment plan provided in the office to a 6
      week education program. Studies indicate that this approach yields benefits for
      patients and their caregivers. Most of these studies involved children and their
      parents or other caregivers, but reduced signs and symptoms of disease and
      improved quality of life also has been documented in adults. Semin Cutan Med Surg
      36(supp4):S106-S107.

PMID- 29659648
TI  - Single-gene prognostic signatures for advanced stage serous ovarian cancer based
      on 1257 patient samples.
AB  - OBJECTIVE: We sought to identify stable single-gene prognostic signatures based
      on a large collection of advanced stage serous ovarian cancer (AS-OvCa) gene
      expression data and explore their functions. METHODS: The empirical Bayes (EB)
      method was used to remove the batch effect and integrate 8 ovarian cancer
      datasets. Univariate Cox regression was used to evaluate the association between
      gene and overall survival (OS). The Database for Annotation, Visualization and
      Integrated Discovery (DAVID) tool was used for the functional annotation of genes
      for Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG)
      pathways. RESULTS: The batch effect was removed by the EB method, and 1257
      patient samples were used for further analysis. We selected 341 single-gene
      prognostic signatures with FDR < 0.05, in which 110 and 231 genes were positively
      and negatively associated with OS, respectively. The functions of these genes
      were mainly involved in extracellular matrix organization, focal adhesion and DNA
      replication which are closely associated with cancer. CONCLUSION: We used the EB
      method to remove the batch effect of 8 datasets, integrated these datasets and
      identified stable prognosis signatures for AS-OvCa.

PMID- 29659649
TI  - Systems analysis of the genetic interaction network of yeast molecular
      chaperones.
AB  - Molecular chaperones are typically promiscuous interacting proteins that function
      globally in the cell to maintain protein homeostasis. Recently, we had carried
      out experiments that elucidated a comprehensive interaction network for the core
      67 chaperones and 15 cochaperones in the budding yeast Saccharomyces cerevisiae
      [Rizzolo et al., Cell Rep., 2017, 20, 2735-2748]. Here, the genetic (i.e.
      epistatic) interaction network obtained for chaperones was further analyzed,
      revealing that the global topological parameters of the resulting network have a
      more central role in mediating interactions in comparison to the rest of the
      proteins in the cell. Most notably, we observed Hsp10, Hsp70 Ssz1 chaperone, and
      Hsp90 cochaperone Cdc37 to be the main drivers of the network architecture.
      Systematic analysis on the physicochemical properties for all chaperone
      interactors further revealed the presence of preferential domains and folds that
      are highly interactive with chaperones such as the WD40 repeat domain. Further
      analysis with established cellular complexes revealed the involvement of R2TP
      chaperone in quaternary structure formation. Our results thus provide a global
      overview of the chaperone network properties in yeast, expanding our
      understanding of their functional diversity and their role in protein
      homeostasis.

PMID- 29659650
TI  - Statistical analysis of multi-dimensional, temporal gene expression of stem cells
      to elucidate colony size-dependent neural differentiation.
AB  - High throughput gene expression analysis using qPCR is commonly used to identify
      molecular markers of complex cellular processes. However, statistical analysis of
      multi-dimensional, temporal gene expression data is complicated by limited
      biological replicates and large number of measurements. Moreover, many available
      statistical tools for analysis of time series data assume that the data sequence
      is static and does not evolve over time. With this assumption, the parameters
      used to model the time series are fixed and thus, can be estimated by pooling
      data together. However, in many cases, dynamic processes of biological systems
      involve abrupt changes at unknown time points, making the assumption of
      stationary time series break down. We addressed this problem using a combination
      of statistical methods including hierarchical clustering, change point detection,
      and multiple testing. We applied this multi-step method to multi-dimensional,
      temporal gene expression data that resulted from our study of colony size
      dependent neural cell differentiation of stem cells. The gene expression data
      were time series as the observations were recorded sequentially over time.
      Hierarchical clustering segregated the genes into three distinct clusters based
      on their temporal expression profiles; change point detection identified specific
      time points at which the entire dataset was divided into several homogenous
      subsets to allow a separate analysis of each subset; and multiple testing
      procedure identified the differentially expressed genes in each cluster within
      each subset of data. We established that our multi-step approach pinpoints
      specific sets of genes that underlie colony size-mediated neural differentiation
      of stem cells and demonstrated its advantages over conventional parametric and
      non-parametric tests that do not take into account temporal dynamics of the data.
      Importantly, our proposed approach is broadly applicable to any multivariate data
      sets of limited sample size from high throughput and high content screening such
      as in drug and biomarker discovery studies.

PMID- 29659651
TI  - STAT3 is required for proliferation and exhibits a cell type-specific binding
      preference in mouse female germline stem cells.
AB  - LIF-mediated STAT3 signaling is critically involved in stem cells and
      development. However, its function in mouse female germline cells (FGSCs) remains
      elusive. In this study, we demonstrated that LIF-induced STAT3 activation
      contributes to the proliferation and undifferentiation maintenance of mouse
      FGSCs. Characterization of the STAT3-mediated transcriptional network by
      intersecting ChIP-seq and RNA-seq datasets revealed 405 direct target genes of
      STAT3, which are primarily involved in proliferation and germline development. In
      particular, we observed that STAT3 exhibits a FGSC-specific binding pattern when
      compared with mouse embryonic stem cells. Taken together, our study reported that
      the LIF-mediated STAT3 activation is actively involved in FGSCs and functions
      through a distinctive binding pattern across the FGSC genome. This cell-type
      specific binding preference provides an insight into understanding the genetic
      base for STAT3-driven cellular functions in germline stem cells.

PMID- 29659654
TI  - LIFE-COURSE LONGITUDINAL STUDIES ARE NEEDED TO ADVANCE INTEGRATION OF GENOMICS
      AND SOCIAL EPIDEMIOLOGY.

PMID- 29659655
TI  - Poor Encoding and Weak Early Consolidation Underlie Memory Acquisition Deficits
      in Multiple Sclerosis: Retroactive Interference, Processing Speed, or Working
      Memory?
AB  - Objective: Learning and memory impairments are common in multiple sclerosis (MS)
      and may be related to difficulty acquiring (encoding or consolidating) new
      information. We evaluate the role of retroactive interference and investigate
      whether minimizing interference immediately following encoding (early during
      consolidation) will improve MS participants' ability to remember new verbal
      information. Additionally, we investigate processing speed differences between
      memory-impaired and unimpaired participants and present an exploratory analysis
      of how the dual-components of working memory (capacity vs. processing) relate to
      memory impairment. Method: MS memory-unimpaired (N = 12) and MS memory-impaired
      participants (N = 12) were compared to healthy controls (N = 15). Interference
      onset following encoding (early, mid, late, no interference) was manipulated over
      the retention interval of a verbal learning and memory task. Response times (RT)
      were recorded during interference trials. Results: MS memory-impaired
      participants encoded less information and lost proportionally more information
      over the retention interval (weak consolidation). Lengthening the onset of
      interference did not benefit memory performance in this sample. Memory
      performance was unrelated to RT but was related to performance on the Symbol
      Digit Modalities Test. Primary capacity of working memory did not differ across
      groups; however, secondary memory processing was reduced for MS memory-impaired
      participants. Conclusion: Minimizing interference following encoding did not
      improve memory in this sample. Both initial encoding and early consolidation were
      reduced for memory-impaired MS participants. Evidence for a relationship between
      processing speed and memory was mixed and depended on the processing speed
      assessment used. Memory impairment in MS may be partially due to inefficient
      processing within working memory.

PMID- 29659656
TI  - Sexual risk-taking and subcortical brain volume in adolescence.
AB  - Background : The developmental period of adolescence marks the initiation of new
      socioemotional and physical behaviors, including sexual intercourse. However,
      little is known about neurodevelopmental influences on adolescent sexual decision
      making. Purpose: We sought to determine how subcortical brain volume correlated
      with condom use, and whether those associations differed by gender and pubertal
      development. Methods: We used FreeSurfer to extract subcortical volume among N =
      169 sexually experienced youth (mean age 16.07 years; 31.95% female). We
      conducted multiple linear regressions to examine the relationship between
      frequency of condom use and subcortical volume, and whether these associations
      would be moderated by gender and pubertal development. Results: We found that the
      relationship between brain volume and condom use was better accounted for by
      pubertal development than by gender, and moderated the association between limbic
      brain volume and condom use. No significant relationships were observed in reward
      areas (e.g., nucleus accumbens) or prefrontal cortical control areas.
      Conclusions: These data highlight the potential relevance of subcortical
      socioemotional processing structures in adolescents' sexual decision-making.

PMID- 29659657
TI  - Prognostic Value of Electrocardiographic Left Ventricular Hypertrophy on
      Cardiovascular Risk in a Non-Hypertensive Community-Based Population.
AB  - BACKGROUND: The appearance of left ventricular hypertrophy on 12-lead
      electrocardiography (ECG-LVH) has been clarified to be associated with the risk
      of incidence of cardiovascular events (CVEs) in hypertensive individuals and the
      general population, but not enough in non-hypertensive individuals. METHODS: A
      total of 4,927 non-hypertensive individuals >=40 years of age who were free of
      CVE in the general population were followed for the incidence of CVE. ECG-LVH was
      defined according to criteria of the Sokolow-Lyon (SL) voltage, Cornell voltage
      (CV), or Cornell voltage product (CP). RESULTS: During the average 9.8 +/- 2.0
      years of follow-up, 267 individuals (5.4%) had their first CVE. The hazard ratio
      (HR) for the incidence of CVE after full adjustment by potential confounders
      significantly increased in the individuals with ECG-LVH by any criteria of the SL
      voltage, CV, and CP (HR = 1.77, P < 0.001) compared to those with no ECG-LVH.
      This association was also significant in individuals without any of obesity,
      dyslipidemia, and diabetes mellitus or those with systolic blood pressure (BP)
      <120 mm Hg and diastolic BP <80 mm Hg. Furthermore, ECG-LVH by each criteria
      provided the reclassification improvement for the CVE risk prediction model by
      the Framingham 10-year risk score (the net reclassification improvement = 0.17
      0.22, each P value < 0.010). CONCLUSIONS: In the absence of hypertension, ECG-LVH
      parameters are associated with the increased risk of developed CVEs independent
      of the established risk factors and provide the additional prognostic value in an
      assessment of the CVE risk using the traditional risk factors.

PMID- 29659658
TI  - Effect of dietary fat intake and genetics on fat taste sensitivity: a co-twin
      randomized controlled trial.
AB  - Background: Individuals with impaired fat taste (FT) sensitivity have reduced
      satiety responses after consuming fatty foods, leading to increased dietary fat
      intake. Habitual consumption of dietary fat may modulate sensitivity to FT, with
      high consumption decreasing sensitivity [increasing fatty acid taste threshold
      (FATT)] and low consumption increasing sensitivity (decreasing FATT). However,
      some individuals may be less susceptible to diet-mediated changes in FATT due to
      variations in gene expression. Objective: The objective of this study was to
      determine the effect of an 8-wk low-fat or high-fat diet on FATT while
      maintaining baseline weight (<2.0 kg variation) to assess heritability and to
      explore the effect of genetics on diet-mediated changes in FATT. Design: A co
      twin randomized controlled trial including 44 pairs (mean +/- SD age: 43.7 +/-
      15.4 y; 34 monozygotic, 10 dizygotic; 33 women, 10 men, 1 gender-discordant) was
      conducted. Twins within a pair were randomly allocated to an 8-wk low-fat (<20%
      of energy from fat) or high-fat (>35% of energy from fat) diet. FATT was assessed
      by a 3-alternate forced choice methodology and transformed to an ordinal scale
      (FT rank) at baseline and at 4 and 8 wk. Linear mixed models were fit to assess
      diet effect on FT rank and diet effect modification due to zygosity. A variance
      components model was fit to calculate baseline heritability. Results: There was a
      significant time * diet interaction for FT rank after the 8-wk trial (P < 0.001),
      with the same conclusions for the subset of participants maintaining baseline
      weight (low-fat; n = 32; high-fat: n = 35). There was no evidence of zygosity
      effect modification (interaction of time * diet * zygosity: P = 0.892).
      Heritability of baseline FT rank was 8%. Conclusions: There appears to be little
      to no genetic contribution on heritability of FATT or diet-mediated changes to
      FATT. Rather, environment, specifically dietary fat intake, is the main
      influencer of FT sensitivity, regardless of body weight. This trial was
      registered with the Australian New Zealand Clinical Trials Registry at
      http://www.anzctr.org.au/ as ACTRN12613000466741.

PMID- 29659659
TI  - An examination of the heterogeneity in the pattern and association between rates
      of change in grip strength and global cognition in late life. A multivariate
      growth mixture modelling approach.
AB  - Background: previous research has demonstrated how older adults exhibit different
      patterns of change in cognitive and physical functioning, suggesting differences
      in the underlying causal processes. Objective: to (i) identify subgroups of older
      adults that best account for different patterns of longitudinal change in
      performance on global cognition and grip strength, (ii) examine the
      interrelationship between global cognition and grip strength trajectories within
      these subgroups and (iii) identify demographic and health-related markers of
      class membership. Methods: multivariate growth mixture models (GMM) were used to
      identify groups of individuals with similar developmental trajectories of muscle
      strength measured by grip strength, and global cognition measured by Mini Mental
      State Examination (MMSE). Results: GMM analyses indicated high, moderate and low
      functioning groups. Individuals in the high and moderate classes demonstrated
      better cognitive and physical functioning at the start of the study and less
      decline than those in the low functioning group. Notably, cognitive performance
      was related to physical functioning at study entry only among individuals in the
      low functioning group. Conclusion: the study demonstrates the applicability of
      the multivariate GMM to achieve a better understanding of the heterogeneity of
      various aging related processes.

PMID- 29659660
TI  - Bioinformatics-guided connection of a biosynthetic gene cluster to the antitumor
      antibiotic gilvusmycin.

PMID- 29659662
TI  - Erratum to "Breastfeeding and Maternal Hypertension".

PMID- 29659661
TI  - RNA and microRNA Stability in PAXgene-Fixed Paraffin-Embedded Tissue Blocks After
      Seven Years' Storage.
AB  - Objectives: To evaluate the stability of RNA and microRNA (miRNA) in PAXgene
      fixed paraffin-embedded tissue blocks after 7 years' storage. Methods: RNA and
      miRNA were extracted from PAXgene-fixed paraffin-embedded (PFPE) blocks in 2009
      then stored at -80 degrees C. Seven years later, RNA and miRNA were again
      extracted from the same blocks. RNA and miRNA integrity in the 2009 and 2016
      extractions were compared using RNA integrity number (RIN), paraffin-embedded RNA
      metric (PERM), reverse transcription polymerase chain reaction (RT-PCR) for
      different amplicon lengths, and quantitative RT-PCR (qRT-PCR) for three mRNA and
      three miRNA targets. Results: In PFPE blocks, mRNA was poorer in 2016 extractions
      compared to the 2009 extractions in all blocks and all assays applied, with
      transcripts degrading at different rates in the same blocks. For miRNA, qRT-PCR
      showed no statistically significant differences between 2009 and 2016
      extractions. Conclusions: mRNA in PFPE tissue blocks degrades at room temperature
      storage over 7 years.

PMID- 29659663
TI  - Real-World Evidence for Regulatory Decisions: Concomitant Administration of
      Zoster Vaccine Live and Pneumococcal Polysaccharide Vaccine.
AB  - The US Food and Drug Administration is charged with expanding the use of real
      world evidence for regulatory decisions. As a test case for real-world evidence
      to support regulatory decisions, we present the scenario of concomitant
      vaccination with zoster vaccine live (ZVL) and 23-valent pneumococcal
      polysaccharide vaccine (PPSV23). The prescribing information states that these
      vaccines should not be given concurrently, based on a small trial using varicella
      zoster virus antibody levels as a correlate of ZVL efficacy, even though ZVL
      protects against herpes zoster via cell-mediated immunity. We conducted an
      observational cohort study involving more than 35,000 members of Kaiser
      Permanente Southern California receiving concomitant ZVL and PPSV23 versus PPSV23
      prior to ZVL. Occurrence of herpes zoster was assessed through electronic health
      records from January 1, 2007, to June 30, 2016. The adjusted hazard ratio
      comparing incidence rates of herpes zoster in the concomitant vaccination cohort
      and the prior vaccination cohort was 1.04 (95% confidence interval: 0.92, 1.16).
      This real-world evidence study provides direct evidence for a lack of vaccine
      interference, relying on herpes zoster occurrence rather than an intermediate
      marker of immunity. Real-world evidence is essential for regulators and policy
      makers in addressing evidentiary gaps regarding safety, effectiveness,
      compliance, and vaccine interactions for the new recombinant zoster vaccine.

PMID- 29659665
TI  - The Influence of Cognitive Reserve on Recovery from Traumatic Brain Injury.
AB  - Objective: we sought to determine the degree to which cognitive reserve, as
      assessed by the Test of Premorbid Functioning in combination with demographic
      variables, could act as a buffer against the effect of traumatic brain injury
      (TBI) on cognitive test performance. Method: retrospective analysis of a cohort
      of 121 persons with TBI who completed the Wechsler Adult Intelligence Scale
      Fourth Edition (WAIS-IV) within 1-12 months after injury. Results: regression
      analyses indicated that cognitive reserve was a statistically significant
      predictor of all postinjury WAIS-IV factor index scores, after controlling for
      various premorbid and comorbid confounding variables. Only for Processing Speed
      did injury severity make an additional statistically significant contribution to
      the prediction model. Conclusions: cognitive reserve has a protective effect with
      regard to the impact of TBI on cognitive test performance but this effect is
      imperfect and does not completely negate the effect of injury severity.

PMID- 29659664
TI  - Depletion of sucrose induces changes in the tip growth mechanism of tobacco
      pollen tubes.
AB  - Background and Aims: Pollen tubes are rapidly growing, photosynthetically
      inactive cells that need high rates of energy to support growth. Energy can
      derive from internal and external storage sources. The lack of carbon sources can
      cause various problems during pollen tube growth, which in turn could affect the
      reproduction of plants. Methods: We analysed the effects of energy deficiency on
      the development of Nicotiana tabacum pollen tubes by replacing sucrose with
      glycerol in the growth medium. We focused on cell growth and related processes,
      such as metabolite composition and cell wall synthesis. Key Results: We found
      that the lack of sucrose affects pollen germination and pollen tube length during
      a specific growth period. Both sugar metabolism and ATP concentration were
      affected by sucrose shortage when pollen tubes were grown in glycerol-based
      media; this was related to decreases in the concentrations of glucose, fructose
      and UDP-glucose. The intracellular pH and ROS levels also showed a different
      distribution in pollen tubes grown in sucrose-depleted media. Changes were also
      observed at the cell wall level, particularly in the content and distribution of
      two enzymes related to cell wall synthesis (sucrose synthase and callose
      synthase). Furthermore, both callose and newly secreted cell wall material
      (mainly pectins) showed an altered distribution corresponding to the lack of
      oscillatory growth in pollen tubes. Growth in glycerol-based media also
      temporarily affected the movement of generative cells and, in parallel, the
      deposition of callose plugs. Conclusion: Pollen tubes represent an ideal model
      system for studying metabolic pathways during the growth of plant cells. In our
      study, we found evidence that glycerol, a less energetic source for cell growth
      than sucrose, causes critical changes in cell wall deposition. The evidence that
      different aspects of pollen tube growth are affected is an indication that pollen
      tubes adapt to metabolic stress.

PMID- 29659666
TI  - Reliable Digit Span: Does it Adequately Measure Suboptimal Effort in an Adult
      Epilepsy Population?
AB  - Objective: Assessment of performance validity is a necessary component of any
      neuropsychological evaluation. Prior research has shown that cutoff scores of <=6
      or <=7 on Reliable Digit Span (RDS) can detect suboptimal effort across numerous
      adult clinical populations; however, these scores have not been validated for
      that purpose in an adult epilepsy population. This investigation aims to
      determine whether these previously established RDS cutoff scores could detect
      suboptimal effort in adults with epilepsy. Method: Sixty-three clinically
      referred adults with a diagnosis of epilepsy or suspected seizures were
      administered the Digit Span subtest of the Wechsler Adult Intelligence Scale
      (WAIS-III or WAIS-IV). Most participants (98%) passed Trial 2 of the Test of
      Memory Malingering (TOMM), achieving a score of >=45. Results: Previously
      established cutoff scores of <=6 and <=7 on RDS yielded a specificity rate of 85%
      and 77% respectively. Findings also revealed that RDS scores were positively
      related to attention and intellectual functioning. Given the less than ideal
      specificity rate associated with each of these cutoff scores, together with their
      strong association to cognitive factors, secondary analyses were conducted to
      identify more optimal cutoff scores. Preliminary results suggest that an RDS
      cutoff score of <=4 may be more appropriate in a clinically referred adult
      epilepsy population with a low average IQ or lower. Conclusions: Preliminary
      findings indicate that cutoff scores of <=6 and <=7 on RDS are not appropriate in
      adults with epilepsy, especially in individuals with low average IQ or below.

PMID- 29659667
TI  - Exploration of older people's perceptions of behavioural factors associated with
      falls.
AB  - Background: falls rates in older people continue to rise despite concerted
      efforts to manage falls risks. As more effective strategies to reduce falls in
      older people may arise from better understanding their perspectives on falls
      risk, this study aimed to explore perceptions and behavioural decisions that may
      affect risk of falling among older people living in regional Australia. Method:
      this qualitative research, informed by hermeneutics, explored older people's
      perspectives on decisions they made that could affect their falls risk. The study
      involved 26 participants (21 females) aged 65-84 years, residing in regional
      Australia. In total, 13 participated in semi-structured focus groups and 13 in
      semi-structured, in-depth interviews. Results: six key themes illuminated the
      challenges older people faced in relation to falls risk. These were: the role
      that independence played in decision making regarding risk; the influence of
      previous falls experience; older people's level of understanding of risks;
      ability and willingness to engage with support; the need or desire to cover up a
      fall history; and the influence of finances in managing risk. Older people's
      accounts demonstrated they experienced competing influences that impacted upon
      decisions they made with respect to falls risks. Most significantly, the complex
      interplay of these influences drove the decisions older people made, sometimes
      placing them at greater risk of falling. Conclusion: consideration of the
      multifaceted issues older people face when managing falls risk, and the influence
      these factors have on their behaviours, is vital to successfully reducing rates
      of fall related injuries in this population.

PMID- 29659668
TI  - Cytology cell blocks are suitable for immunohistochemical testing for PD-L1 in
      lung cancer.
AB  - Background: PD-L1 immunohistochemistry (IHC) testing is usually carried out on
      tissue blocks from core needle biopsy or surgical resections. In this study, we
      assessed the feasibility of using cytology cell blocks for PD-L1 IHC assay.
      Methods: A total of 1419 consecutive cases of non-small-cell lung cancer (NSCLC),
      including 371 cytology cell blocks, 809 small biopsies, and 239 surgical
      specimens, were included in the study. The cytology cell blocks were prepared
      with formalin only, methanol/alcohol only or both. PD-L1 expression was examined
      by staining with Dako PD-L1 IHC 22C3 pharmDx kit. A Tumor Proportion Score (TPS)
      was categorized as <1%, 1%-49% and >=50% tumor cells. A total of 100 viable tumor
      cells were required for adequacy. Results: Of the cytology cell blocks, 92% of
      the specimens had an adequate number of tumor cells, not significantly different
      from small biopsies. The rate of TPS >=50% differed between sample types and was
      observed in 42% of cytology cell blocks versus 36% of small biopsies (P = 0.04),
      and 29% of surgical resections (P = 0.001). The fixative methods did not affect
      the immunostaining, with overall PD-L1 high expression (TPS >=50%) rates of 42%
      in formalin-fixed specimens versus 40% in specimens with combined fixation by
      methanol/alcohol and formalin (NS). The PD-L1 high expression rate was not
      associated with EGFR, ALK or KRAS molecular alterations. Higher stage (IV) was
      associated with higher PD-L1 TPS (P= 0.001). Conclusion: Our results show that
      when the TPS >=50% is used as the end point, PD-L1 IHC performs well with
      cytology cell blocks. Cell blocks should be considered as a valuable resource for
      PD-L1 testing in advanced NSCLC. The clinical significance of higher PD-L1 IHC
      scores in cytology specimens needs to be evaluated prospectively.

PMID- 29659669
TI  - Overexpression of FIBCD1 Is Predictive of Poor Prognosis in Gastric Cancer.
AB  - Objectives: Fibrinogen C domain containing 1 (FIBCD1) is a newly identified
      acetyl group recognition receptor. The aim of this study was to evaluate the
      prognostic significance of FIBCD1 in gastric cancer. Methods: This study included
      706 samples, and the clinical data of all patients were recorded in detail. We
      studied messenger RNA (mRNA) and protein expression of FIBCD1 in cancerous and
      normal tissues by quantitative real-time polymerase chain reaction (n = 54) and
      tissue microarray immunohistochemistry analysis (n = 706), respectively. Results:
      mRNA and protein expression levels of FIBCD1 were significantly higher in gastric
      cancer than in normal tissues. High FIBCD1 protein level showed significant
      correlations with age (P = .011), TNM stage (P < .001), serum carcinoembryonic
      antigen (CEA) level (P = .002), and the expression of human epidermal growth
      factor receptor 2 (P < .001). Kaplan-Meier survival analysis revealed that
      patients with gastric cancer with high levels of FIBCD1 had a significantly
      shorter survival time than those with low expression levels. In univariate
      analysis, high FIBCD1 expression, older age, histologic type, differentiation,
      TNM stage, serum CEA, and serum CA19-9 level correlated with overall survival.
      Multivariate analysis suggested that FIBCD1 expression was an independent
      prognostic factor. Conclusions: FIBCD1 may be a novel biomarker to evaluate the
      prognosis of gastric cancer.

PMID- 29659670
TI  - Histone deacetylase SIRT6 inhibits glioma cell growth through down-regulating
      NOTCH3 expression.
AB  - Gliomas are the most common brain tumors of the central nervous system. In this
      study, we investigated the molecular mechanisms and biological function of SIRT6
      in human gliomas. The expression levels of SIRT6 in glioma tissues and cells were
      analyzed by qRT-PCR and western blot analysis. CCK8 and clonogenicity assays were
      performed to detect the cell proliferation. Furthermore, the migration and
      invasion of glioma cells were examined by transwell assays. It was found that the
      expression of SIRT6 was significantly lower in human glioma tissues or cell lines
      compared with the normal brain tissue or NHA. Up-regulated SIRT6 significantly
      decreased cell proliferation, migration and invasion of U87 and U251 cells. By
      contrast, knockdown of SIRT6 dramatically increased cell proliferation, migration
      and invasion of U87 and U251 cells. Moreover, over expression of NOTCH3
      significantly increased the cell proliferation, migration, and invasion of U87
      and U251 cells. However, these effects were abolished after overexpression of
      SIRT6. These results suggest that SIRT6 may suppress cell proliferation,
      migration, and invasion via inhibition of the NOTCH3 signaling pathway in glioma.

PMID- 29659671
TI  - Early life determinants of frailty in old age: the Helsinki Birth Cohort Study.
AB  - Background: there is evidence suggesting that several chronic diseases have their
      origins in utero and that development taking place during sensitive periods may
      affect the aging process. We investigated whether early life determinants would
      be associated with frailty in old age. Methods: at a mean age of 71 years, 1,078
      participants belonging to the Helsinki Birth Cohort Study were assessed for
      frailty according to the Fried frailty criteria. Early life measurements (birth
      weight, length, mother body mass index [BMI] and parity) were obtained from
      birth, child welfare and school health records. Multinomial regression analysis
      was used to assess the association between early life determinants and frailty in
      old age. Results: weight, length and BMI at birth were all inversely associated
      with frailty in old age. A 1 kg increase in birth weight was associated with a
      lower relative risk ratio (RRR) of frailty (age and sex-adjusted RRR = 0.40, 95%
      CI: 0.19, 0.82) compared to non-frailty. Associations persisted after adjusting
      for several confounding factors. Compared to cohort members in the upper middle
      class, those who as adults worked as manual workers or belonged to the lower
      middle class, were at an increased risk of frailty. Conclusions: those who were
      small at birth were at an increased risk of developing frailty in old age,
      suggesting that frailty is at least partly programmed in early life. A less
      privileged socioeconomic status in adulthood was associated with an increased
      risk of frailty in old age.

PMID- 29659672
TI  - Phase III randomized study of second line ADI-PEG 20 plus best supportive care
      versus placebo plus best supportive care in patients with advanced hepatocellular
      carcinoma.
AB  - Background: Arginine depletion is a putative target in hepatocellular carcinoma
      (HCC). HCC often lacks argininosuccinate synthetase, a citrulline to arginine
      repleting enzyme. ADI-PEG 20 is a cloned arginine degrading enzyme-arginine
      deiminase-conjugated with polyethylene glycol. The goal of this study was to
      evaluate this agent as a potential novel therapeutic for HCC after first line
      systemic therapy. Methods and patients: Patients with histologically proven
      advanced HCC and Child-Pugh up to B7 with prior systemic therapy, were randomized
      2 : 1 to ADI-PEG 20 18 mg/m2 versus placebo intramuscular injection weekly. The
      primary end point was overall survival (OS), with 93% power to detect a 4-5.6
      months increase in median OS (one-sided alpha = 0.025). Secondary end points
      included progression-free survival, safety, and arginine correlatives. Results: A
      total of 635 patients were enrolled: median age 61, 82% male, 60% Asian, 52%
      hepatitis B, 26% hepatitis C, 76% stage IV, 91% Child-Pugh A, 70% progressed on
      sorafenib and 16% were intolerant. Median OS was 7.8 months for ADI-PEG 20 versus
      7.4 for placebo (P = 0.88, HR = 1.02) and median progression-free survival 2.6
      months versus 2.6 (P = 0.07, HR = 1.17). Grade 3 fatigue and decreased appetite
      occurred in <5% of patients. Two patients on ADI-PEG 20 had >=grade 3
      anaphylactic reaction. Death rate within 30 days of end of treatment was 15.2% on
      ADI-PEG 20 versus 10.4% on placebo, none related to therapy. Post hoc analyses of
      arginine assessment at 4, 8, 12 and 16 weeks, demonstrated a trend of improved OS
      for those with more prolonged arginine depletion. Conclusion: ADI-PEG 20
      monotherapy did not demonstrate an OS benefit in second line setting for HCC. It
      was well tolerated. Strategies to enhance prolonged arginine depletion and
      synergize the effect of ADI-PEG 20 are underway. Clinical Trial number:
      www.clinicaltrials.gov (NCT 01287585).

PMID- 29659673
TI  - Evaluation of the Utility of Bone Marrow Morphology and Ancillary Studies in
      Pediatric Patients Under Surveillance for Myelodysplastic Syndrome.
AB  - Objectives: To evaluate the utility of flow cytometry, karyotype, and a
      fluorescence in situ hybridization (FISH) panel in screening children for
      myelodysplastic syndrome (MDS). Methods: Bone marrow morphology, flow cytometry,
      karyotype, and FISH reports from 595 bone marrow specimens (246 patients) were
      analyzed. Results: By morphology, 8.7% of cases demonstrated at least unilineage
      dysplasia and/or increased blasts. Flow cytometry identified definitive
      abnormalities in 2.8% of cases, all of which had abnormal morphology. Of the 42
      cases (7.2%) with acquired karyotypic abnormalities, 26 had no morphologic
      dysplasia. With a 98.2% concordance between karyotype and MDS FISH, FISH only
      identified two additional cases, both with low-level (<4%) abnormalities.
      Peripheral blood count evaluation only identified the absence of thrombocytopenia
      to correlate with an absence of abnormal ancillary tests. Conclusions: The
      combination of morphologic evaluation and karyotype with judicious use of flow
      cytometry and MDS FISH is sufficient to detect abnormalities for these
      indications.

PMID- 29659674
TI  - GETTING SERIOUS ABOUT EMBODIMENT: CAUTIONS ABOUT INTERPRETING NOVEL FINDINGS OF
      SOCIOECONOMIC PATTERNS IN BIOLOGICAL FUNCTION.

PMID- 29659675
TI  - Facing the Inevitable: Being Prepared for Regulatory Requirements for Laboratory
      Developed Tests.
AB  - Objectives: We introduce regulatory terms, definitions, and the Quality System
      Regulation as proposed by the US Food and Drug Administration in the 2014 draft
      guidance entitled Framework for Regulatory Oversight of Laboratory Developed
      Tests and explore medical device requirements applicable to a laboratory
      environment to design, develop, and validate laboratory developed tests (LDTs).
      Methods: We performed nine interviews with laboratory professionals to explore
      concerns and challenges regarding the draft, translated the results into
      operational factors, and surveyed professionals to test the factors that would
      comprise a regulatory quality management system framework. Results: Nine
      interviewees and 35 survey respondents shared concerns of risk classification,
      process validation, patient safety, and general ambiguity regarding the proposed
      requirements for development of LDTs. Conclusions: Respondents agree that a
      regulatory quality management system is needed in laboratories that develop LDTs,
      but the translation and method for design control to a clinical laboratory do not
      exist. As a result, laboratories are taking the wait-and-see approach.

PMID- 29659676
TI  - Methodology of clinical trials evaluating the incorporation of new drugs in the
      first-line treatment of patients with diffuse large B-cell lymphoma (DLBCL): a
      critical review.
AB  - Background: The first-line treatment of diffuse large B-cell lymphoma (DLBCL) is
      the combination of rituximab with CHOP (cyclophosphamide, doxorubicin,
      vincristine, prednisone) chemotherapy, curing approximately 60% of patients. Many
      clinical trials have been carried out over the last 10 years trying to improve
      the results of this treatment, but the appropriateness of their planning
      strategies could be rediscussed. Patients and methods: Reports of phase III
      trials evaluating the addition of molecularly targeted agents or new monoclonal
      antibodies to the classic R-CHOP backbone in first-line induction or maintenance
      treatment were reviewed. The trial design, primary end point, number of patients
      enrolled, patient selection criteria, treatment schedule and results were
      registered for each one. In addition, the phases I and II trials which preceded
      these phase III trials were also reviewed. Results: Among six phase III trials
      with results, only one trial evaluating lenalidomide maintenance after response
      to R-CHOP induction was positive and reached its primary end point. The other
      five trials did not show an improved outcome with the addition of the new agent.
      The preceding phases I and II trials were very heterogeneous in their end points
      and design. Even though most of these trials were considered positive, thus
      encouraging further investigation, so far they failed to predict the results of
      the subsequent phase III trials. Conclusion: The standard of care for DLBCL is
      still R-CHOP. Phase I/II trials failed to predict the results of subsequent phase
      III trials evaluating non-chemotherapeutic agents added to R-CHOP. The
      methodology of phase II trials evaluating new agents in DLBCL needs to be better
      defined in the future.

PMID- 29659678
TI  - Test Cost and Test Accuracy in Clinical Laboratories in Kampala, Uganda.
AB  - Objectives: To assess the accuracy and costs of laboratory tests in Kampala,
      Uganda. Methods: A random selection of 78 laboratories tested external quality
      assurance samples at market rates. There were 40 moderate- to high-complexity and
      38 low-complexity laboratories. Four percent (3/78) of these laboratories were
      accredited and 94% (73/78) were private. The 40 moderate- to high-complexity
      laboratories performed malaria blood smear, urine human chorionic gonadotropin
      (hCG), human immunodeficiency virus (HIV), syphilis, glucose, and three-panel
      tests: CBC, liver function tests, and kidney function tests. The 38 low
      complexity laboratories performed malaria blood smear, urine hCG, and syphilis
      testing only. Hematology, HIV, syphilis, and malarial proficiency testing samples
      were prepared by accredited laboratories in Kampala. All other samples were
      provided by the Royal College of Pathologists of Australia. Results: 77.1% of all
      results were accurate (met target values). It varied widely by laboratory (50%
      100%), test identity (malaria blood smear, 96%; serum urea nitrogen, 38%), and
      test type (quantitative: 66% [31%-89%], qualitative: 91% [68%-97%]). Test prices
      varied by up to 3,600%, and there was no correlation between test cost and
      accuracy (r2 = 0.02). Conclusions: There were large differences in accuracy and
      price across laboratories in Kampala. Price was not associated with quality.

PMID- 29659677
TI  - Targeting the human epidermal growth factor receptor 2 (HER2) oncogene in
      colorectal cancer.
AB  - Human epidermal growth factor receptor 2 (HER2) is an oncogenic driver, and a
      well-established therapeutic target in breast and gastric cancers. Using
      functional and genomic analyses of patient-derived xenografts, we previously
      showed that a subset (approximately 5%) of metastatic colorectal cancer (CRC)
      tumors is driven by amplification or mutation of HER2. This paper reviews the
      role of HER2 amplification as an oncogenic driver, a prognostic and predictive
      biomarker, and a clinically actionable target in CRC, considering the specifics
      of HER2 testing in this tumor type. While the role of HER2 as a biomarker for
      prognosis in CRC remains uncertain, its relevance as a therapeutic target has
      been established. Indeed, independent studies documented substantial clinical
      benefit in patients treated with biomarker-driven HER2-targeted therapies, with
      an impact on response rates and duration of response that compared favorably with
      immunotherapy and other examples of precision oncology. HER2-targeted therapeutic
      strategies have the potential to change the treatment paradigm for a clinically
      relevant subgroup of metastatic CRC patients.

PMID- 29659679
TI  - Surveillance imaging with FDG-PET/CT in the post-operative follow-up of stage 3
      melanoma.
AB  - Background: As early detection of recurrent melanoma maximizes treatment options,
      patients usually undergo post-operative imaging surveillance, increasingly with
      FDG-PET/CT (PET). To assess this, we evaluated stage 3 melanoma patients who
      underwent prospectively applied and sub-stage-specific schedules of PET
      surveillance. Patients and methods: From 2009, patients with stage 3 melanoma
      routinely underwent PET +/- MRI brain scans via defined schedules based on sub
      stage-specific relapse probabilities. Data were collected regarding patient
      characteristics and outcomes. Contingency analyses were carried out of imaging
      outcomes. Results: One hundred and seventy patients (stage 3A: 34; 3B: 93; 3C:
      43) underwent radiological surveillance. Relapses were identified in 65 (38%)
      patients, of which 45 (69%) were asymptomatic. False-positive imaging findings
      occurred in 7%, and 6% had treatable second (non-melanoma) malignancies. Positive
      predictive values (PPV) of individual scans were 56%-83%. Negative scans had
      predictive values of 89%-96% for true non-recurrence [negative predictive values
      (NPV)] until the next scan. A negative PET at 18 months had NPVs of 80%-84% for
      true non-recurrence at any time in the 47-month (median) follow-up period.
      Sensitivity and specificity of the overall approach of sub-stage-specific PET
      surveillance were 70% and 87%, respectively. Of relapsed patients, 33 (52%)
      underwent potentially curative resection and 10 (16%) remained disease-free after
      24 months (median). Conclusions: Application of sub-stage-specific PET in stage 3
      melanoma enables asymptomatic detection of most recurrences, has high NPVs that
      may provide patient reassurance, and is associated with a high rate of detection
      of resectable and potentially curable disease at relapse.

PMID- 29659680
TI  - Reply to the letter to the editor 'ESMO-MCBS v1.1: statistical and patient
      relevant shortcomings' by Emprechtinger et al.

PMID- 29659681
TI  - Snacking Recommendations Worldwide: A Scoping Review.
AB  - Across the globe, dietary habits include the consumption of foods and drinks
      between main meals. Although often described as "snacks" or "snacking," there is
      no scientific consensus of what constitutes a snack, either as an eating occasion
      or as a snack food. Nonetheless, food-based dietary guidelines, compiled at
      national or regional levels by governments, learned societies, and health
      organizations, frequently refer to snacking habits and desirable or undesirable
      snack food choices. This review aims to provide a comprehensive snapshot of
      snacking recommendations worldwide. From a search of 207 countries and
      organizations, 49 countries and 7 regional or global organizations were
      identified that referred to snacks, snack foods, or snacking. A total of 136
      snacking-specific recommendations or examples were identified, which varied in
      nature whereby some provided advice on the quality of the snack food choice and
      others focused on the frequency or energy and nutrient composition of such
      snacks. Guidelines varied in terms of the detail of foods and drinks identified,
      wherein some recommendations focused only on foods or food categories to include
      (e.g., fruit or dairy) or to exclude (e.g., processed foods), whereas other
      recommendations made reference to both. Both individual foods (e.g., apples) and
      food categories (e.g., fruit) were mentioned. Reasons or rationales to support
      the snacking choices were less frequently identified and varied across regions.
      It is hoped that this analysis will stimulate discussion on the need for a
      consensus in the scientific community and beyond with regard to snacking. An
      agreed-upon definition of snacks, snacking, and snack foods could be used to
      inform a number of stakeholders and ultimately help consumers adhere to healthful
      diets as defined locally.

PMID- 29659682
TI  - Xanthophylls.

PMID- 29659683
TI  - Review of 100% Fruit Juice and Chronic Health Conditions: Implications for Sugar
      Sweetened Beverage Policy.
AB  - Whether or not drinking 100% fruit juice causes poor health is controversial.
      Although 100% fruit juice may contain as much sugar as regular soda, it provides
      needed nutrients to Americans' diets. We systematically reviewed the current
      evidence of the association of 100% fruit juice consumption and chronic health
      conditions in children and adults. We focused on data from systematic reviews and
      meta-analyses about cardiometabolic health outcomes, liver disease, and caries.
      Aside from increased risk of tooth decay in children and small amounts of weight
      gain in young children and adults, there is no conclusive evidence that
      consumption of 100% fruit juice has adverse health effects. Guidelines from
      groups like the American Academy of Pediatrics and Dietary Guidelines for
      Americans recommending that 100% fruit juice may be consumed in moderation are
      consistent with the available evidence and should be used to inform food
      policies.

PMID- 29659684
TI  - omega-3 Fatty Acids, Impaired Fetal Growth, and Cardiovascular Risk: Nutrition as
      Precision Medicine.
AB  - Precision medicine refers to treatment or prevention strategies in a group of
      individuals identified by their phenotype or genotype. Dietary components or
      patterns may play an important role in precision medicine. There is emerging
      evidence to support a role for n-3 (omega-3) fatty acids in lowering blood
      pressure and reducing the extent of subclinical atherosclerosis in people born
      with impaired fetal growth, a group at increased risk of coronary artery disease
      partly due to an increased risk of hypertensive disorders. The evidence linking n
      3 fatty acid intake with less atherosclerosis and lower blood pressure in people
      with impaired fetal growth has been derived from studies in young children,
      adolescents, and adults and has included dietary assessments by questionnaires
      and circulating biomarkers. Furthermore, results appear to be similar for shorter
      chain n-3 fatty acids from plant sources and long-chain n-3 fatty acids from
      marine sources. The general framework used to develop this evidence, consisting
      of hypothesis-driven analyses from observational studies and post hoc analyses of
      a randomized clinical trial, before a priori testing as a primary outcome in
      randomized trials, is presented and proposed as a potential model for the
      identification and development of dietary precision medicine strategies.

PMID- 29659686
TI  - Erratum: Food groups and risk of hypertension: a systematic review and dose
      response meta-analysis of prospective studies.

PMID- 29659685
TI  - Can Curcumin Counteract Cognitive Decline? Clinical Trial Evidence and Rationale
      for Combining omega-3 Fatty Acids with Curcumin.
AB  - The rate of cognitive decline in the elderly is highly variable. One potential
      factor contributing to accelerated cognitive decline is chronic systemic
      inflammation, because it has been linked to cognitive impairment and increased
      dementia risk. Certain lifestyle factors, such as excess body weight and
      sedentary behavior, can exacerbate a proinflammatory state in older adults,
      resulting in chronic low-grade inflammation. Supplementing the diet with
      curcumin, an anti-inflammatory polyphenolic compound from the curry spice
      turmeric, is a potential approach to prevent accelerated cognitive decline by
      counteracting chronic inflammatory processes. Although the anti-inflammatory
      effects of curcumin are well established, the potential cognitive benefits of
      curcumin were discovered more recently. Several animal and epidemiologic studies
      on the effect of curcumin supplementation on cognition showed promising results;
      however, randomized controlled trials in humans are limited. In this review, we
      identified 5 randomized controlled trials, of which only 2 observed a beneficial
      effect of curcumin supplementation on cognition by improving working memory. By
      critically examining the methodologies of those studies, we identified some
      limitations, one of which is that none of the studies explored the possibility
      that anti-inflammatory mechanisms were mediating cognitive benefits (i.e., no
      study tested participants with low-grade inflammation or measured inflammatory
      biomarkers). Other factors influencing the likelihood of conclusive outcomes
      include choice of study population (cognitively unimpaired compared with
      impaired), study duration, curcumin dose and its bioavailability, and
      neurocognitive test battery. On the basis of these findings, we offer
      recommendations for future studies to examine the potential cognitive benefits of
      curcumin in humans, which include evaluating its effects on cerebral endothelial
      vasodilator function and boosting its cognitive effects by combining it with long
      chain omega-3 (n-3) fatty acids.

PMID- 29659688
TI  - Thriving, Not Just Surviving: Skills Essential to Leveraging Your Scientific
      Career.

PMID- 29659687
TI  - Obesity Interventions for Older Adults: Diet as a Determinant of Physical
      Function.
AB  - Throughout the world, a high prevalence of obesity in older populations has
      created a new phenotype of frailty: the obese, functionally frail older adult.
      The convergence of the obesity epidemic with global graying will undoubtedly
      increase the prevalence of this concern. Barriers to treatment include
      ambiguities about the appropriate level of obesity that should trigger an
      intervention, due to age-related physiologic changes and a lack of consensus on
      specific criteria and cutoffs. Moreover, obesity interventions for this
      population have been limited by concerns about negative effects on lean mass,
      bone mineral density, and even mortality. However, newly reported approaches for
      restoring physical function by obesity reduction have shown good short-term
      efficacy. Because the majority of these interventions have used exercise as part
      of the treatment, this review focuses specifically on current understanding of
      the discrete effects of dietary interventions for geriatric obesity with regards
      to functional outcomes on tests including the Short Physical Performance Battery,
      the Physical Performance Test, and the Western Ontario and McMaster Universities
      Osteoarthritis Index. The literature showed roughly equal benefits to function
      from a weight reduction diet or exercise regimen, although neither modality was
      as efficacious alone as the 2 combined. Only 1 of 3 studies of protein intake
      during weight loss showed a positive effect of protein on function, but findings
      to date are too limited to prove or disprove a protein benefit. We conclude that
      although diet and exercise should be combined whenever possible, it remains
      important to further investigate the beneficial and likely unique effects that
      calorie restriction and/or nutrient modification can provide, particularly for
      obese and functionally frail older populations.

PMID- 29659689
TI  - Perspective: Total, Added, or Free? What Kind of Sugars Should We Be Talking
      About?
AB  - There is consistent public guidance to limit sugars intakes. However, WHO
      recommendations are for "free" sugars, whereas some other guidance documents and
      public discussion focus on "added" sugars, and globally most food labeling states
      "total" sugars. Total sugars comprise all mono- and disaccharides, regardless of
      source, whereas both added and free sugars exclude the sugars that naturally
      occur in dairy products and intact fruit and vegetables. Definitions of added and
      free sugars differ mainly in their respective exclusion or inclusion of sugars in
      juiced or pureed fruit and vegetables. To date, there has been little evidence
      based analysis of the scientific basis for these different sugar classifications
      or implications of their adoption for consumer communication and nutrition
      labeling. Evidence of discriminating relations of total compared with added or
      free sugars with weight gain or energy intake, type 2 diabetes, and dental caries
      was identified from recent systematic reviews and meta-analyses. The relations
      were weakest for total sugars and most consistent for dietary sources
      corresponding to free sugars (including sugars added to and in fruit juices).
      Consideration of these health outcomes suggests that the emphasis for intake
      monitoring, public health guidance, and consumer communication should be on free
      sugars. However, at present, the adoption of free sugars for these purposes would
      also carry challenges related to implementation, including consumer
      understanding, consensus on specifications, and current (labeling) regulations.

PMID- 29659690
TI  - Perspective: Challenges and Controversial Issues in the Dietary Guidelines for
      Americans, 1980-2015.
AB  - Since 1980, every edition of the Dietary Guidelines for Americans (DGAs) has
      recommended increased consumption of fruits, vegetables, and whole grains, but
      reduced consumption of saturated fat, sugars, and sodium and, therefore, their
      primary food sources. Every edition has generated controversy, mainly from
      producers of foods affected by "eat less" recommendations, particularly meat.
      Objections to the 2015 DGAs focused on environmental as well as scientific
      issues, but also on purported conflicts of interest among members of the Dietary
      Guidelines Advisory Committee. On this basis, critics induced Congress to
      authorize the National Academy of Medicine (NAM) to review the process of drawing
      up the guidelines. The NAM's 2017 reports should strengthen the process, but as
      long as science continues to support advice to reduce consumption of targeted
      foods, the guidelines will continue to elicit political controversy.

PMID- 29659691
TI  - Perspective: Cardiovascular Responses to Sugar-Sweetened Beverages in Humans: A
      Narrative Review with Potential Hemodynamic Mechanisms.
AB  - Cardiovascular diseases are still the primary cause of mortality worldwide, with
      high blood pressure and type 2 diabetes as major promoters. Over the past 3
      decades, almost in parallel with the rise in cardiovascular disease incidence,
      the consumption of sugar-sweetened beverages (SSBs) has increased. In this
      context, SSBs are potential contributors to weight gain and increase the risk for
      elevations in blood pressure, type 2 diabetes, coronary heart disease, and
      stroke. Nevertheless, the mechanisms underlying the cardiovascular and metabolic
      responses to SSBs, in particular on blood pressure, are poorly understood. We
      discuss and propose potential mechanisms underlying differential effects of
      sugars on postprandial blood pressure regulation; provide evidence for additional
      molecular contributors, i.e., fibroblast growth factor 21, towards sugar-induced
      cardiovascular responses; and discuss potential cardiovascular neutral sugars.
      Furthermore, we explore whether pre-existing glucose intolerance in humans
      exacerbates the cardiovascular responses to SSBs, thus potentially aggravating
      the cardiovascular risk in already-susceptible individuals.

PMID- 29659693
TI  - The History and Future of Dietary Guidance in America.
AB  - Evidence-based dietary guidance in the United States has progressed substantially
      since its inception >100 y ago. This review describes the historical development
      and significance of dietary guidance in the United States, including the Dietary
      Guidelines for Americans (DGAs), and emphasizes the foundations upon which they
      were developed, the process in the formation of past and current guidelines, and
      present and future applications. Dietary guidance during the first half of the
      20th century was focused primarily on food groups in a healthy diet, food safety,
      safe food storage, and the role of some minerals and vitamins in the prevention
      of disease. This was punctuated by World War II messaging to reduce food waste
      and increase food storage. In 1980, the first DGA report was released, and later,
      the USDA and the Department of Health and Human Services (HHS) were given a
      mandate for reissuance and reassessment every 5 y. An ad hoc advisory committee
      made up of nongovernmental experts was established for each edition to review the
      scientific evidence and provide content recommendations to the Secretaries of the
      USDA and the HHS. Wording was changed from negative (avoid) to positive (choose)
      and emphasis was increasingly placed on reducing the prevalence of overweight and
      obesity and prevention of chronic diseases. Today, the DGAs guide all federally
      funded feeding and educational programs, including food policies, food assistance
      programs, and consumer education programs, as well as these programs at the
      regional, state, and local levels. Additional users include dietitians and other
      health professionals, food service personnel, food and beverage manufacturers,
      schools, and day care facilities. Currently, the DGAs are intended for
      individuals aged >=2 y. Future editions of the DGAs will include guidance for
      infants and children <2 y, as well as pregnant women.

PMID- 29659692
TI  - Bone Health following Bariatric Surgery: Implications for Management Strategies
      to Attenuate Bone Loss.
AB  - Bariatric surgery (BS) is an effective treatment for morbid obesity and its
      associated comorbidities. Following such a procedure, however, patients are at
      risk of developing metabolic bone disease owing to the combination of rapid
      weight loss, severely restricted dietary intake, and reduced intestinal nutrient
      absorption. Patients undergoing malabsorptive procedures are at a higher risk of
      postoperative bone health deterioration than those undergoing restrictive
      procedures; however, studies have demonstrated negative skeletal consequences of
      restrictive procedures as well. The clinical practice guidelines of some
      international associations have previously addressed preoperative evaluation and
      postoperative clinical care in order to maintain bone health in BS patients.
      Nevertheless, some issues regarding bone health in BS patients remain unclear
      owing to the lack of relevant randomized clinical trials, including doses of
      nutritional supplements pre- and post-BS. This review summarizes the current data
      regarding the skeletal consequences of BS and its mechanisms, with an emphasis on
      the preventive strategies and nutritional care that may be warranted in order to
      attenuate bone deterioration following BS.

PMID- 29659694
TI  - Nutritional Genomics and Direct-to-Consumer Genetic Testing: An Overview.
AB  - The increasing prevalence in polygenic diseases, such as obesity, cardiovascular
      disease, and type 2 diabetes, observed over the past few decades is more likely
      linked to a rapid transition in lifestyle rather than to changes in the sequence
      of the nuclear genome. In the new era of precision medicine, nutritional genomics
      holds the promise to be translated into tailored nutritional strategies to
      prevent and manage polygenic diseases more effectively. Nutritional genomics aims
      to prevent, treat, and manage polygenic diseases through targeted therapies
      formulated from individuals' genetic makeup and dietary intake. Direct-to
      consumer genetic testing (DTC-GT) has become commercially available to equip
      individuals with information on their genetic vulnerability to different
      diseases. This information may potentially prompt behavioral changes against
      adverse factors. However, scientific evidence behind the clinical recommendations
      is a matter of continuous debate, and behavioral modifications after disclosing
      genetic information remain inconclusive. In this review, we provide an overview
      of nutritional genomics and related nutritional DTC-GT services and discuss
      whether available data are sufficient to be translated into clinical
      recommendations and public health initiatives. Overall, the scientific evidence
      supporting the dissemination of genomic information for nutrigenomic purposes
      remains sparse. Therefore, additional knowledge needs to be generated,
      particularly for polygenic traits.

PMID- 29659696
TI  - An Alternative to the Lateral Direct Browlift.

PMID- 29659695
TI  - DeepSimulator: a deep simulator for Nanopore sequencing.
AB  - Motivation: Oxford Nanopore sequencing is a rapidly developed sequencing
      technology in recent years. To keep pace with the explosion of the downstream
      data analytical tools, a versatile Nanopore sequencing simulator is needed to
      complement the experimental data as well as to benchmark those newly developed
      tools. However, all the currently available simulators are based on simple
      statistics of the produced reads, which have difficulty in capturing the complex
      nature of the Nanopore sequencing procedure, the main task of which is the
      generation of raw electrical current signals. Results: Here we propose a deep
      learning based simulator, DeepSimulator, to mimic the entire pipeline of Nanopore
      sequencing. Starting from a given reference genome or assembled contigs, we
      simulate the electrical current signals by a context-dependent deep learning
      model, followed by a base-calling procedure to yield simulated reads. This
      workflow mimics the sequencing procedure more naturally. The thorough experiments
      performed across four species show that the signals generated by our context
      dependent model are more similar to the experimentally obtained signals than the
      ones generated by the official context-independent pore model. In terms of the
      simulated reads, we provide a parameter interface to users so that they can
      obtain the reads with different accuracies ranging from 83 to 97%. The reads
      generated by the default parameter have almost the same properties as the real
      data. Two case studies demonstrate the application of DeepSimulator to benefit
      the development of tools in de novo assembly and in low coverage SNP detection.
      Availability and implementation: The software can be accessed freely at:
      https://github.com/lykaust15/DeepSimulator. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 29659697
TI  - Variations in leaf growth parameters within the tree structure of adult Coffea
      arabica in relation to seasonal growth, water availability and air carbon dioxide
      concentration.
AB  - Background and Aims: Dynamics in branch and leaf growth parameters, such as the
      phyllochron, duration of leaf expansion, leaf life span and bud mortality,
      determine tree architecture and canopy foliage distribution. We aimed to estimate
      leaf growth parameters in adult Arabica coffee plants based on leaf supporter
      axis order and position along the vertical profile, considering their
      modifications related to seasonal growth, air [CO2] and water availability.
      Methods: Growth and mortality of leaves and terminal buds of adult Arabica coffee
      trees were followed in two independent field experiments in two sub-tropical
      climate regions of Brazil, Londrina-PR (Cfa) and Jaguariuna-SP (Cwa). In the Cwa
      climate, coffee trees were grown under a FACE (free air CO2 enrichment) facility,
      where half of those had been irrigated. Plants were observed at a 15-30 d
      frequency for 1 year. Leaf growth parameters were estimated on five axes orders
      and expressed as functions of accumulated thermal time ( degrees Cd per leaf).
      Key Results: The phyllochron and duration of leaf expansion increased with axis
      order, from the seond to the fourth. The phyllochron and life span during the
      reduced vegetative seasonal growth were greater than during active growth. It
      took more thermal time for leaves from the first- to fourth-order axes to expand
      their blades under irrigation compared with rainfed conditions. The compensation
      effects of high [CO2] for low water availability were observed on leaf retention
      on the second and third axes orders, and duration of leaf expansion on the first-
      and fourth-order axes. The second-degree polynomials modelled leaf growth
      parameter distribution in the vertical tree profile, and linear regressions
      modelled the proportion of terminal bud mortality. Conclusions: Leaf growth
      parameters in coffee plants were determined by axis order. The duration of leaf
      expansion contributed to phyllochron determination. Leaf growth parameters varied
      according the position of the axis supporter along the vertical profile,
      suggesting an effect of axes age and micro-environmental light modulations.

PMID- 29659698
TI  - Molecular subtyping of cancer: current status and moving toward clinical
      applications.
AB  - Cancer is a collection of genetic diseases, with large phenotypic differences and
      genetic heterogeneity between different types of cancers and even within the same
      cancer type. Recent advances in genome-wide profiling provide an opportunity to
      investigate global molecular changes during the development and progression of
      cancer. Meanwhile, numerous statistical and machine learning algorithms have been
      designed for the processing and interpretation of high-throughput molecular data.
      Molecular subtyping studies have allowed the allocation of cancer into
      homogeneous groups that are considered to harbor similar molecular and clinical
      characteristics. Furthermore, this has helped researchers to identify both
      actionable targets for drug design as well as biomarkers for response prediction.
      In this review, we introduce five frequently applied techniques for generating
      molecular data, which are microarray, RNA sequencing, quantitative polymerase
      chain reaction, NanoString and tissue microarray. Commonly used molecular data
      for cancer subtyping and clinical applications are discussed. Next, we summarize
      a workflow for molecular subtyping of cancer, including data preprocessing,
      cluster analysis, supervised classification and subtype characterizations.
      Finally, we identify and describe four major challenges in the molecular
      subtyping of cancer that may preclude clinical implementation. We suggest that
      standardized methods should be established to help identify intrinsic subgroup
      signatures and build robust classifiers that pave the way toward stratified
      treatment of cancer patients.

PMID- 29659699
TI  - A Different Perspective on Breast Implant Surface Texturization and Anaplastic
      Large Cell Lymphoma (ALCL).
AB  - Anaplastic large cell lymphoma (ALCL) is a rare form of lymphoma involving cells
      of the immune system. It is currently gaining interest because of an association
      between the development of ALCL and an increased risk in women who have had
      breast implant surgery. Although not confirmed, many theories exist as to the
      etiology of this association in women, and there is growing concern that ALCL is
      more prevalent in women with textured breast implants. In particular, the risk of
      developing ALCL appears to be related to increasing implant texturization or
      "surface roughness." This paper examines the current manner of defining and
      characterizing breast implant surface texture and challenges the appropriateness
      of applying this technology and linking it to ALCL. It is not a comprehensive
      review of the etiology of capsular contracture and ALCL, but it proposes an
      alternative perspective on surface texture measurements from that currently
      employed and its role in researching the etiology of ALCL. The authors hope that
      their article will provoke thought and reflection when considering the issues
      currently being highlighted with regard to texturing of breast implants.

PMID- 29659700
TI  - Sex steroids drive the remodeling of oviductal extracellular matrix in cattle.
AB  - The extracellular matrix (ECM) is a group of molecules that offer structural and
      biochemical support to cells and interact with them to regulate their function.
      Also, growth factors (GFs) stored in the ECM can be locally released during ECM
      remodeling. Here, we hypothesize that the balance between ECM components and
      remodelers is regulated according to the ovarian steroid milieu to which the
      oviduct is exposed during the periovulatory period. Follicular growth was
      manipulated to generate cows that ovulated small follicles (SF-small corpus
      luteum [SCL]; n = 20) or large follicles (LF-large corpus luteum [LCL]; n = 21)
      and possess corresponding Estradiol (E2) and Progesterone (P4) plasmatic
      concentrations. Ampulla and isthmus samples were collected on day 4 (day 0 =
      ovulation induction) and immediately frozen or fixed. The transcriptional profile
      (n = 3/group) was evaluated by RNA sequencing. MMP Antibody Array was used to
      quantify ECM remodelers' protein abundance and immunohistochemistry to quantify
      type I collagen. Transcriptome analysis revealed the over-representation of ECM
      organization and remodeling pathways in the LF-LCL group. Transcription of ECM
      components (collagens), remodelers (ADAMs and MMPs), and related GFs were
      upregulated in LF-LCL. Protein intensities for MMP3, MMP8, MMP9, MMP13, and TIMP4
      were greater for the LF-LCL group. Type I collagen content in the mucosa was
      greater in SF-SCL group. In conclusion, that the earlier and more intense
      exposure to E2 and P4 during the periovulatory period in LF-LCL animals
      stimulates ECM remodeling. We speculate that differential ECM regulation may
      contribute to oviductal receptivity to the embryo.

PMID- 29659701
TI  - Gain-of-function mutation of AtDICE1, encoding a putative endoplasmic reticulum
      localized membrane protein, causes defects in anisotropic cell elongation by
      disturbing cell wall integrity in Arabidopsis.
AB  - Background and Aims: Anisotropic cell elongation depends on cell wall relaxation
      and cellulose microfibril arrangement. The aim of this study was to characterize
      the molecular function of AtDICE1 encoding a novel transmembrane protein involved
      in anisotropic cell elongation in Arabidopsis. Methods: Phenotypic
      characterizations of transgenic Arabidopsis plants mis-regulating AtDICE1
      expression with different pharmacological treatments were made, and biochemical,
      cell biological and transcriptome analyses were performed. Key Results:
      Upregulation of AtDICE1 in Arabidopsis (35S::AtDICE1) resulted in severe
      dwarfism, probably caused by defects in anisotropic cell elongation. Epidermal
      cell swelling was evident in all tissues, and abnormal secondary wall thickenings
      were observed in pith cells of stems. These phenotypes were reproduced not only
      by inducible expression of AtDICE1 but also by overexpression of its poplar
      homologue in Arabidopsis. RNA interference suppression lines of AtDICE1 resulted
      in no observable phenotypic changes. Interestingly, wild-type plants treated with
      isoxaben, a cellulose biosynthesis inhibitor, phenocopied the 35S::AtDICE1
      plants, suggesting that cellulose biosynthesis was compromised in the
      35S::AtDICE1 plants. Indeed, disturbed cortical microtubule arrangements in
      35S::AtDICE1/GFP-TuA6 plants were observed, and the cellulose content was
      significantly reduced in 35S::AtDICE1 plants. A promoter::GUS analysis showed
      that AtDICE1 is mainly expressed in vascular tissue, and transient expression of
      GFP:AtDICE1 in tobacco suggests that AtDICE1 is probably localized in the
      endoplasmic reticulum (ER). In addition, the external N-terminal conserved domain
      of AtDICE1 was found to be necessary for AtDICE1 function. Whole transcriptome
      analyses of 35S::AtDICE1 revealed that many genes involved in cell wall
      modification and stress/defence responses were mis-regulated. Conclusions:
      AtDICE1, a novel ER-localized transmembrane protein, may contribute to
      anisotropic cell elongation in the formation of vascular tissue by affecting
      cellulose biosynthesis.

PMID- 29659702
TI  - Ribopeaks: a web tool for bacterial classification through m/z data from
      ribosomal proteins.
AB  - Summary: MALDI-TOF MS is a rapid, sensitive and economic tool for bacterial
      identification. Highly abundant bacterial proteins are detected by this
      technique, including ribosomal proteins (r-protein), and the generated mass
      spectra are compared with a MALDI-TOF MS spectra database. Currently, it allows
      mainly the classification of clinical bacteria due to the limited number of
      environmental bacteria included in the spectra database. We present a wide
      ranging bacterium classifier tool, called Ribopeaks, which was created based on r
      protein data from the Genbank. The Ribopeaks database has more than 28 500
      bacterial taxonomic records. It compares the incoming m/z data from MALDI-TOF MS
      analysis with models stored in the Ribopeaks database created by machine learning
      and then taxonomically classifies the bacteria. Availability and implementation:
      The software is available at http://www.ribopeaks.com. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 29659703
TI  - B-cell receptor reconstruction from single-cell RNA-seq with VDJPuzzle.
AB  - Motivation: The B-cell receptor (BCR) performs essential functions for the
      adaptive immune system including recognition of pathogen-derived antigens. The
      vast repertoire and adaptive variation of BCR sequences due to V(D)J
      recombination and somatic hypermutation necessitates single-cell characterization
      of BCR sequences. Single-cell RNA sequencing presents the opportunity for
      simultaneous capture of paired BCR heavy and light chains and the transcriptomic
      signature. Results: We developed VDJPuzzle, a novel bioinformatic tool that
      reconstructs productive, full-length B-cell receptor sequences of both heavy and
      light chains and extract somatic mutations on the VDJ region. VDJPuzzle
      successfully reconstructed BCRs from 100% (n=117) human and 96.5% (n=200) murine
      B cells. The reconstructed BCRs were successfully validated with single-cell
      Sanger sequencing. Availability and implementation: VDJPuzzle is available at
      https://bitbucket.org/kirbyvisp/vdjpuzzle2. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 29659704
TI  - Development of the sphagnoid areolation pattern in leaves of Palaeozoic
      protosphagnalean mosses.
AB  - Background and Aims: Protosphagnalean mosses constitute the largest group of
      extinct mosses of still uncertain affinity. Having the general morphology of the
      Bryopsida, some have leaves with an areolation pattern characteristic of modern
      Sphagna. This study describes the structure and variation of these patterns in
      protosphagnalean mosses and provides a comparison with those of modern Sphagna.
      Methods: Preparations of fossil mosses showing preserved leaf cell structure were
      obtained by dissolving rock, photographed, and the resulting images were
      transformed to graphical format and analysed with Areoana computer software. Key
      Results: The sphagnoid areolation pattern is identical in its basic structure for
      both modern Sphagnum and Palaeozoic protosphagnalean mosses. However, in the
      former group the pattern develops through unequal oblique cell divisions, while
      in the latter the same pattern is a result of equal cell divisions taking place
      in a specific order with subsequent uneven cell growth. The protosphagnalean
      pathway leads to considerable variability in leaf structure. Conclusions:
      Protosphagnalean mosses had a unique ability to switch the development of leaf
      areolation between a pathway unique to Sphagnum and another one common to all
      other mosses. This developmental polyvariancy hinders attempts to classify these
      mosses, as characters previously considered to be of generic significance can be
      shown to co-occur in one individual leaf. New understanding of the ontogeny has
      allowed us to re-evaluate the systematic significance of such diagnostic
      characters in these Palaeozoic plants, showing that their similarity to Sphagnum
      is less substantial.

PMID- 29659705
TI  - IRscope: an online program to visualize the junction sites of chloroplast
      genomes.
AB  - Motivation: Genome plotting is performed using a wide range of visualizations
      tools each with emphasis on a different informative dimension of the genome.
      These tools can provide a deeper insight into the genomic structure of the
      organism. Results: Here, we announce a new visualization tool that is
      specifically designed for chloroplast genomes. It allows the users to depict the
      genetic architecture of up to ten chloroplast genomes in the vicinity of the
      sites connecting the inverted repeats to the short and long single copy regions.
      The software and its dependent libraries are fully coded in R and the reflected
      plot is scaled up to realistic size of nucleotide base pairs in the vicinity of
      the junction sites. We introduce a website for easier use of the program and R
      source code of the software to be used in case of preferences to be changed and
      integrated into personal pipelines. The input of the program is an annotation
      GenBank (.gb) file, the accession or GI number of the sequence or a DOGMA output
      file. The software was tested using over a 100 embryophyte chloroplast genomes
      and in all cases a reliable output was obtained. Availability and implementation:
      Source codes and the online suit available at https://irscope.shinyapps.io/irapp/
      or https://github.com/Limpfrog/irscope.

PMID- 29659706
TI  - Body Composition Remodeling and Incident Mobility Limitations in African Ancestry
      Men.
AB  - Background: Mobility limitations are common, with higher prevalence in African
      Americans compared to whites, and are associated with disability,
      institutionalization and death. Aging is associated with losses of lean mass and
      a shift to central adiposity, which are more pronounced in African Americans. We
      aimed to examine the association of body composition remodeling with incident
      mobility limitations in older men of African Ancestry. Methods: Seven-year
      changes in body composition were measured using peripheral computed tomography
      (pQCT) of the calf and whole-body dual x-ray absorptiometry (DXA) in 505 African
      Ancestry men aged >=60 years and free of self-reported mobility limitations at
      baseline. Self-reported incident mobility limitations were assessed at 7-year
      follow-up. Odds of developing mobility limitations associated with baseline and
      change in body composition were quantified using separate logistic regression
      models. Results: Seventy-five men (14.9%) developed incident mobility limitations
      over 6.2+/-0.6 years. Baseline body composition was not associated with incident
      mobility limitations. After adjustment for covariates, gaining total and
      intermuscular fat were associated with incident mobility limitations a (OR: 1.60;
      95% CI: 1.21-2.13; OR: 1.51; 95% CI: 1.18-1.94). Changes in DXA lean mass were
      not related to mobility limitations; however, maintaining pQCT calf muscle area
      was protective against mobility limitations (OR: 0.65; 95% CI: 0.48-0.87).
      Conclusions: Increases in body fat, and particularly intermuscular fat, and
      decreases in calf skeletal muscle were associated with a higher risk of
      developing mobility limitations. Our findings emphasize the importance of body
      composition remodeling in the development of mobility limitations among African
      ancestry men.

PMID- 29659708
TI  - PhyloProfile: dynamic visualization and exploration of multi-layered phylogenetic
      profiles.
AB  - Summary: Phylogenetic profiles form the basis for tracing proteins and their
      functions across species and through time. Novel genome sequences nowadays often
      represent species from the remotest corner of the tree of life. Thus,
      phylogenetic profiling becomes increasingly important for functionally annotating
      this data and to integrate it into a comprehensive view on organismal evolution.
      To strengthen the link between the sharing of a gene across species and of the
      corresponding function, it is meanwhile common to complement phylogenetic
      profiles with additional information, such as domain architecture similarities
      between orthologs, or pairwise similarities of other protein features. However,
      there are few visualization tools that facilitate an intuitive integration of
      these various information layers. Here, we present PhyloProfile, an R-based tool
      to visualize, explore and analyze multi-layered phylogenetic profiles.
      Availability and implementation: PhyloProfile is available as open source code
      under the MIT license at https://github.com/BIONF/phyloprofile. An online version
      for testing PhyloProfile and for small to medium-scale analyses is available at
      http://applbio.biologie.uni-frankfurt.de/phyloprofile.

PMID- 29659707
TI  - Therapist-Client Interactions in Motivational Interviewing: The Effect of
      Therapists' Utterances on Client Change Talk.
AB  - Aims: Motivational Interviewing is an effective treatment for a range of
      problematic behaviours, however, previous studies have revealed substantial
      variability in the effectiveness of therapists. Curiously, the specific
      behaviours which contribute to positive outcomes have rarely been studied. The
      aim of this study was to investigate hypothesised relationships between
      therapists' utterances and clients' change talk by analysing interactions sampled
      from the United Kingdom Alcohol Treatment Trial (UKATT). Methods: This study
      comprised secondary analysis of process data and recordings selectively sampled
      from the UKATT database using sequential analyses of utterance categories,
      defined using the Motivational Interviewing Sequential Code for Observing Process
      Exchanges (MI-SCOPE). MI-SCOPE categories were modified on the basis of the
      existing literature. Observed and expected frequencies of change talk,
      transitional probabilities and their significance levels both immediately
      following therapists' statements (Lag 1), and after a delay (Lag 2) were
      calculated using the Generalised Sequential Querier (GSEQ) programme. Regression
      analyses were conducted using SPSS 21.0. Results: In successful alcohol treatment
      sessions, therapists' open questions and complex reflections were significantly
      positively associated with client preparatory talk at Lag 1. Therapists' complex
      reflections were significantly positively associated with and predictive of
      strong client commitment talk at Lag 2. Conclusions: The findings extend those of
      previous studies, suggesting that open questions and complex reflections play a
      central role in preparing clients for, and facilitating strong commitment to,
      behaviour change.

PMID- 29659709
TI  - Progress in single-access information systems for wheat and rice crop
      improvement.
AB  - Improving productivity of the staple crops wheat and rice is essential to feed
      the growing global population, particularly in the context of a changing climate.
      However, current rates of yield gain are insufficient to support the predicted
      population growth. New approaches are required to accelerate the breeding
      process, and many of these are driven by the application of large-scale crop
      data. To leverage the substantial volumes and types of data that can be applied
      for precision breeding, the wheat and rice research communities are working
      towards the development of integrated systems to access and standardize the
      dispersed, heterogeneous available data. Here, we outline the initiatives of the
      International Wheat Information System (WheatIS) and the International Rice
      Informatics Consortium (IRIC) to establish Web-based single-access systems and
      data mining tools to make the available resources more accessible, drive
      discovery and accelerate the production of new crop varieties. We discuss the
      progress of WheatIS and IRIC towards unifying specialized wheat and rice
      databases and building custom software platforms to manage and interrogate these
      data. Single-access crop information systems will strengthen scientific
      collaboration, optimize the use of public research funds and help achieve the
      required yield gains in the two most important global food crops.

PMID- 29659710
TI  - SnapperDB: a database solution for routine sequencing analysis of bacterial
      isolates.
AB  - Summary: Real-time surveillance of infectious disease using whole genome
      sequencing data poses challenges in both result generation and communication.
      SnapperDB represents a set of tools to store bacterial variant data and
      facilitate reproducible and scalable analysis of bacterial populations. We also
      introduce the 'SNP address' nomenclature to describe the relationship between
      isolates in a population to the single nucleotide resolution. We announce the
      release of SnapperDB v1.0 a program for scalable routine SNP analysis and storage
      of microbial populations. Availability and implementation: SnapperDB is
      implemented as a python application under the open source BSD license. All code
      and user guides are available at https://github.com/phe-bioinformatics/snapperdb.
      Reference genomes and SnapperDB configs are available at https://github.com/phe
      bioinformatics/snapperdb_references.

PMID- 29659711
TI  - Corrigendum: Real-time monitoring using a breathalyzer-based eHealth system can
      identify lapse/relapse patterns in alcohol use disorder patients.

PMID- 29659712
TI  - Visually-sensitive networks in essential tremor: evidence from structural and
      functional imaging.

PMID- 29659713
TI  - Primary Squamous Cell Carcinoma Arising From a Breast Implant Capsule: A Case
      Report and Review of the Literature.
AB  - Level of Evidence 5: 

PMID- 29659714
TI  - Computation and application of tissue-specific gene set weights.
AB  - Motivation: Gene set testing, or pathway analysis, has become a critical tool for
      the analysis of high-dimensional genomic data. Although the function and activity
      of many genes and higher-level processes is tissue-specific, gene set testing is
      typically performed in a tissue agnostic fashion, which impacts statistical power
      and the interpretation and replication of results. Results: To address this
      challenge, we have developed a bioinformatics approach to compute tissue-specific
      weights for individual gene sets using information on tissue-specific gene
      activity from the Human Protein Atlas (HPA). We used this approach to create a
      public repository of tissue-specific gene set weights for 37 different human
      tissue types from the HPA and all collections in the Molecular Signatures
      Database. To demonstrate the validity and utility of these weights, we explored
      three different applications: the functional characterization of human tissues,
      multi-tissue analysis for systemic diseases and tissue-specific gene set testing.
      Availability and implementation: All data used in the reported analyses is
      publicly available. An R implementation of the method and tissue-specific weights
      for MSigDB gene set collections can be downloaded at
      http://www.dartmouth.edu/~hrfrost/TissueSpecificGeneSets.

PMID- 29659715
TI  - The cost-effectiveness of follow-up strategies after cancer treatment: a
      systematic literature review.
AB  - Introduction: The cost of treatment and follow-up of cancer patients in the UK is
      substantial. In a budget-constrained system such as the NHS, it is necessary to
      consider the cost-effectiveness of the range of management strategies at
      different points on cancer patients' care pathways to ensure that they provide
      adequate value for money. Sources of data: We conducted a systematic literature
      review to explore the cost-effectiveness of follow-up strategies of patients
      previously treated for cancer with the aim of informing UK policy. All papers
      that were considered to be economic evaluations in the subject areas described
      above were extracted. Areas of agreement: The existing literature suggests that
      intensive follow-up of patients with colorectal disease is likely to be cost
      effective, but the opposite holds for breast cancer. Areas of controversy:
      Interventions and strategies for follow-up in cancer patients were variable
      across type of cancer and setting. Drawing general conclusions about the cost
      effectiveness of these interventions/strategies is difficult. Growing points: The
      search identified 2036 references but applying inclusion/exclusion criteria a
      total of 44 articles were included in the analysis. Breast cancer was the most
      common (n = 11) cancer type followed by colorectal (n = 10) cancer. In general,
      there were relatively few studies of cost-effectiveness of follow-up that could
      influence UK guidance. Where there was evidence, in the most part, NICE guidance
      broadly reflected this evidence. Areas timely to develop research: In terms of
      future research around the timing, frequency and composition of follow-ups, this
      is dependent on the type of cancer being considered. Nevertheless, across most
      cancers, the possibility of remote follow-up (or testing) by health professionals
      other than hospital consultants in other settings appears to warrant further
      work.

PMID- 29659716
TI  - The Effect of Smoking in the Cosmetic Surgery Population: Analysis of 129,007
      Patients.
AB  - Background: Smoking has been associated with several postoperative adverse
      outcomes across multiple surgical disciplines, but the literature is limited for
      aesthetic surgical procedures. Objectives: To compare complication rates between
      smokers and nonsmokers undergoing common cosmetic procedures, identify specific
      cosmetic procedures where smoking increases the risk of complications, and
      evaluate smoking as an independent risk factor for major complications following
      aesthetic surgery. Methods: A prospective cohort of patients undergoing cosmetic
      surgery between 2008 and 2013 was identified from the CosmetAssureTM database.
      Smoking was evaluated as a risk factor for major complications requiring
      emergency room visit, hospital admission, or reoperation within 30 days after
      surgery. Multivariate regression analysis was performed controlling for the
      effects of age, gender, body mass index, type of surgical facility, type of
      procedure, and combined procedures. Results: Of the 129,007 patients, 10,621
      (8.2%) were smokers. All procedures examined, except breast augmentation, were
      more frequently performed in the nonsmoker cohort. Overall major complications
      were similar between smokers and nonsmokers (2.0% vs 1.9%, p=0.57). In univariate
      analysis, surgical site infections (0.6% vs 0.5%, p=0.04) were significantly
      higher among smokers, but suspected venous thromboembolism (0.2% vs 0.1%, p=0.01)
      significantly higher among nonsmokers. Notably, smokers had a higher risk of
      major complications after body procedures (2.9% vs 1.0%, p=0.01), as well as
      thigh lifts (23.8% vs 3.6%, p<0.01) and male breast surgery (3.7% vs 1.4%,
      p=0.03). In multivariate analysis, smoking was found to be an independent
      predictor of surgical site infections (relative risk 1.61, p<0.01). Conclusions:
      Smoking is an independent risk factor of major surgical site infections following
      aesthetic surgery. Body procedures, as well as thigh lifts and male breast
      surgery have higher complication rates in smokers.

PMID- 29659717
TI  - Statin Treatment Is Associated With a Neutral Effect on Health-Related Quality of
      Life Among Community-Dwelling Octogenarian Men: The Helsinki Businessmen Study.
AB  - Background: Statin treatment is common among 80+ people, but little is known
      about statin effects on health-related quality of life (HRQoL) in this oldest age
      group. Methods: In the Helsinki Businessmen Study (HBS), men born from 1919 to
      1934 (original n = 3,490), have been followed-up since the 1960s. In 2015, a
      questionnaire about lifestyle, diseases, and medications, and including RAND
      36/SF-36 HRQoL instrument was mailed to survivors. About 612 men (72.6%)
      responded, 530 of them reporting their medications (98% community-living).
      Propensity score analysis was used to compare statin users and nonusers for
      HRQoL. Results: We compared 229 current statin users (median age 85 years,
      interquartile range 84-88 years) with 301 nonusers (86; 84-89 years). Current
      statin users had had significantly higher serum cholesterol level in midlife (p <
      .001), but current lifestyle-related characteristics were similar in users and
      nonusers. Statin users reported more hypertension (61.1%, p < .001), diabetes
      (23.6%, p <.001), and atherosclerotic cardiovascular disease (ASCVD, 33.6%, p
      <.001), than nonusers. Statin users reported higher mean scores than nonusers in
      all eight RAND-36 subscales, but after adjustments for multiplicity and a
      propensity score we found no significant differences between statin users and
      nonusers. Stratification for primary (no ASCVD) and secondary (with CVD)
      prevention supported the main results. Conclusions: Our study suggests that
      statin treatment has no significant effect on health-related quality of life
      among octogenarian, community-dwelling men. The results contradict concerns about
      statin treatment in the oldest-old, and may caution against deprescribing of
      statins due to old age alone.

PMID- 29659718
TI  - A sequence family database built on ECOD structural domains.
AB  - Motivation: The ECOD database classifies protein domains based on their
      evolutionary relationships, considering both remote and close homology. The
      family group in ECOD provides classification of domains that are closely related
      to each other based on sequence similarity. Due to different perspectives on
      domain definition, direct application of existing sequence domain databases, such
      as Pfam, to ECOD struggles with several shortcomings. Results: We created
      multiple sequence alignments and profiles from ECOD domains with the help of
      structural information in alignment building and boundary delineation. We
      validated the alignment quality by scoring structure superposition to demonstrate
      that they are comparable to curated seed alignments in Pfam. Comparison to Pfam
      and CDD reveals that 27 and 16% of ECOD families are new, but they are also
      dominated by small families, likely because of the sampling bias from the PDB
      database. There are 35 and 48% of families whose boundaries are modified
      comparing to counterparts in Pfam and CDD, respectively. Availability and
      implementation: The new families are now integrated in the ECOD website. The
      aggregate HMMER profile library and alignment are available for download on ECOD
      website (http://prodata.swmed.edu/ecod). Supplementary information: Supplementary
      data are available at Bioinformatics online.

PMID- 29659719
TI  - pysster: classification of biological sequences by learning sequence and
      structure motifs with convolutional neural networks.
AB  - Summary: Convolutional neural networks (CNNs) have been shown to perform
      exceptionally well in a variety of tasks, including biological sequence
      classification. Available implementations, however, are usually optimized for a
      particular task and difficult to reuse. To enable researchers to utilize these
      networks more easily, we implemented pysster, a Python package for training CNNs
      on biological sequence data. Sequences are classified by learning sequence and
      structure motifs and the package offers an automated hyper-parameter optimization
      procedure and options to visualize learned motifs along with information about
      their positional and class enrichment. The package runs seamlessly on CPU and GPU
      and provides a simple interface to train and evaluate a network with a handful
      lines of code. Using an RNA A-to-I editing dataset and cross-linking
      immunoprecipitation (CLIP)-seq binding site sequences, we demonstrate that
      pysster classifies sequences with higher accuracy than previous methods, such as
      GraphProt or ssHMM, and is able to recover known sequence and structure motifs.
      Availability and implementation: pysster is freely available at
      https://github.com/budach/pysster. Supplementary information: Supplementary data
      are available at Bioinformatics online.

PMID- 29659720
TI  - MP-LAMP: parallel detection of statistically significant multi-loci markers on
      cloud platforms.
AB  - Summary: Exhaustive detection of multi-loci markers from genome-wide association
      study datasets is a computationally challenging problem. This paper presents a
      massively parallel algorithm for finding all significant combinations of alleles
      and introduces a software tool termed MP-LAMP that can be easily deployed in a
      cloud platform, such as Amazon Web Service, as well as in an in-house computer
      cluster. Multi-loci marker detection is an unbalanced tree search problem that
      cannot be parallelized by simple tree-splitting using generic parallel
      programming frameworks, such as Map-Reduce. We employ work stealing and periodic
      reduce-broadcast to decrease the running time almost linearly to the number of
      cores. Availability and implementation: MP-LAMP is available at
      https://github.com/tsudalab/mp-lamp. Supplementary information: Supplementary
      data are available at Bioinformatics online.

PMID- 29659721
TI  - JAMI: fast computation of conditional mutual information for ceRNA network
      analysis.
AB  - Motivation: Genome-wide measurements of paired miRNA and gene expression data
      have enabled the prediction of competing endogenous RNAs (ceRNAs). It has been
      shown that the sponge effect mediated by protein-coding as well as non-coding
      ceRNAs can play an important regulatory role in the cell in health and disease.
      Therefore, many computational methods for the computational identification of
      ceRNAs have been suggested. In particular, methods based on Conditional Mutual
      Information (CMI) have shown promising results. However, the currently available
      implementation is slow and cannot be used to perform computations on a large
      scale. Results: Here, we present JAMI, a Java tool that uses a non-parametric
      estimator for CMI values from gene and miRNA expression data. We show that JAMI
      speeds up the computation of ceRNA networks by a factor of ~70 compared to
      currently available implementations. Further, JAMI supports multi-threading to
      make use of common multi-core architectures for further performance gain.
      Requirements: Java 8. Availability and implementation: JAMI is available as open
      source software from https://github.com/SchulzLab/JAMI. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 29659722
TI  - A joint spatial factor analysis model to accommodate data from misaligned areal
      units with application to Louisiana social vulnerability.
AB  - With the threat of climate change looming, the public health community has an
      interest in identifying communities at the highest risk of devastation based not
      only on geographic features but also on social characteristics. Indices of
      community social vulnerability can be created by applying a spatial factor
      analysis to a set of relevant social variables measured for each community;
      however, current spatial factor analysis methodology is ill-equipped to handle
      spatially misaligned data. We introduce a joint spatial factor analysis model
      that can accommodate spatial data from two distinct partitions of a geographic
      space and identify a common set of latent factors underlying them. By defining
      the latent factors over the intersection of the two partitions, the model
      minimizes loss of information. Using simulated data constructed to mimic the
      spatial structure of our real data, we confirm the reliability of the model and
      demonstrate its superiority over competing ad hoc methods for dealing with
      misaligned data in spatial factor analysis. Finally, we construct an index of
      community social vulnerability for each census tract in Louisiana, a state prone
      to environmental disasters, which could be exacerbated by climate change, by
      applying the joint spatial factor analysis model to a set of misaligned social
      indicator data from the state. To demonstrate the utility of this index, we
      integrate it with Louisiana flood insurance claims data to identify communities
      that may be at particularly high risk during natural disasters, based on both
      social and geographic features.

PMID- 29659723
TI  - Age-Related Slowing of Contractile Properties Differs Between Power, Endurance,
      and Nonathletes: A Tensiomyographic Assessment.
AB  - Although master athletes maintain high levels of physical activity, they also
      suffer from an age-related decline in skeletal muscle function. There are
      indications of disproportional age- and physical inactivity-induced muscle
      wasting between muscles. Tensiomyography is a noninvasive tool that has been used
      to study the effects of a variety of sports on the contraction time (Tc) in
      different skeletal muscles. The aim of this cross-sectional study was to assess
      age-related changes in the Tc of the vastus lateralis, gastrocnemius medialis,
      and biceps femoris muscles with Tensiomyography in older nonathletes (age = 62.1
      +/- 12.7 years; NMALES = 133; NFEMALES = 246), and power (age = 56.9 +/- 13.5
      years; NMALES = 100; NFEMALES = 78) and endurance master athletes (age = 56.5 +/-
      14.5 years; NMALES = 76; NFEMALES = 73). We found an age-related slowing in all
      muscles, irrespective of discipline, where endurance master athletes had the
      longest and power master athletes had the shortest Tc. The longer Tc in endurance
      master athletes than in nonathletes suggests that regular endurance sport
      activity aggravates slowing of skeletal muscles during aging.

PMID- 29659724
TI  - Efficient population-scale variant analysis and prioritization with VAPr.
AB  - Summary: With the growing availability of population-scale whole-exome and whole
      genome sequencing, demand for reproducible, scalable variant analysis has spread
      within genomic research communities. To address this need, we introduce the
      Python package Variant Analysis and Prioritization (VAPr). VAPr leverages
      existing annotation tools ANNOVAR and MyVariant.info with MongoDB-based flexible
      storage and filtering functionality. It offers biologists and bioinformatics
      generalists easy-to-use and scalable analysis and prioritization of genomic
      variants from large cohort studies. Availability and implementation: VAPr is
      developed in Python and is available for free use and extension under the MIT
      License. An install package is available on PyPi at
      https://pypi.python.org/pypi/VAPr, while source code and extensive documentation
      are on GitHub at https://github.com/ucsd-ccbb/VAPr.

PMID- 29659725
TI  - Bone Morphogenetic Proteins, Satellite Cells, and Sarcopenia: Perspective in
      Translational Medicine.

PMID- 29659726
TI  - Dubious space for Artelon joint resurfacing for basal thumb (trapeziometacarpal
      joint) osteoarthritis. A systematic review.
AB  - Introduction: Trapeziometacarpal arthritis is a common and disabling condition.
      There is no evidence in the literature of superiority of one surgical procedure
      over others. Several prosthetic implants have been introduced to preserve joint
      mobility. Sourced of data: We searched the on Medline (PubMed), Web of Science
      and Scopus databases using the combined keywords 'artelon', 'thumb',
      'carpometacarpal', 'trapeziometacarpal' and 'rhizoarthrosis'; 11 studies were
      identified. Areas of agreement: The use of Artelon implant is not recommended
      because of its high revision rate and worse outcomes compared to conventional
      techniques. Areas of controversy: Inert materials subjected to compressive and
      shearing forces could produce debris and subsequent inflammatory response. There
      is debate in the published scientific literature regarding the role of
      preoperative antibiotic profilaxis and post-surgery inflammatory response.
      Growing points: Standard techniques such as trapeziectomy alone or combined with
      interposition or suspensionplasty offer effective treatment for thumb basal joint
      arthritis. Areas timely for developing research: Several prosthetic implants show
      promising results in terms of pain relief and functional request, but there is a
      need of long-term randomized controlled trials to demonstrate their equivalence,
      and eventually superiority, compared to standard techniques.

PMID- 29659727
TI  - Nitrite circumvents platelet resistance to nitric oxide in patients with heart
      failure preserved ejection fraction and chronic atrial fibrillation.
AB  - Aims: Heart failure (HF) is a pro-thrombotic state. Both platelet and vascular
      responses to nitric oxide (NO) donors are impaired in HF patients with reduced
      ejection fraction (HFrEF) compared with healthy volunteers (HVs) due to
      scavenging of NO, and possibly also reduced activity of the principal NO sensor,
      soluble guanylate cyclase (sGC), limiting the therapeutic potential of NO donors
      as anti-aggregatory agents. Previous studies have shown that nitrite inhibits
      platelet activation presumptively after its reduction to NO, but the mechanism(s)
      involved remain poorly characterized. Our aim was to compare the effects of
      nitrite on platelet function in HV vs. HF patients with preserved ejection
      fraction (HFpEF) and chronic atrial fibrillation (HFpEF-AF), vs. patients with
      chronic AF without HF, and to assess whether these effects occur independent of
      the interaction with other formed elements of blood. Methods and results:
      Platelet responses to nitrite and the NO donor sodium nitroprusside (SNP) were
      compared in age-matched HV controls (n = 12), HFpEF-AF patients (n = 29), and
      chronic AF patients (n = 8). Anti-aggregatory effects of nitrite in the presence
      of NO scavengers/sGC inhibitor were determined and vasodilator-stimulated
      phosphoprotein (VASP) phosphorylation was assessed using western blotting. In HV
      and chronic AF, both nitrite and SNP inhibited platelet aggregation in a
      concentration-dependent manner. Inhibition of platelet aggregation by the NO
      donor SNP was impaired in HFpEF-AF patients compared with healthy and chronic AF
      individuals, but there was no impairment of the anti-aggregatory effects of
      nitrite. Nitrite circumvented platelet NO resistance independently of other blood
      cells by directly activating sGC and phosphorylating VASP. Conclusion: We here
      show for the first time that HFpEF-AF (but not chronic AF without HF) is
      associated with marked impairment of platelet NO responses due to sGC dysfunction
      and nitrite circumvents the 'platelet NO resistance' phenomenon in human HFpEF,
      at least partly, by acting as a direct sGC activator independent of NO.

PMID- 29659728
TI  - Racial Disparities in Invasive Methicillin-resistant Staphylococcus aureus
      Infections, 2005-2014.
AB  - Background: Despite substantial attention to the individual topics, little is
      known about the relationship between racial disparities and antimicrobial
      resistant and/or healthcare-associated infection trends, such as for methicillin
      resistant Staphylococcus aureus (MRSA). Methods: We analyzed Emerging Infections
      Program 2005-2014 surveillance data (9 US states) to determine whether reductions
      in invasive MRSA incidence (isolated from normally sterile body sites) affected
      racial disparities in rates. Case classification included hospital-onset (HO,
      culture >3 days after admission), healthcare-associated community onset (HACO,
      culture <=3 days after admission and dialysis, hospitalization, surgery, or long
      term care residence within 1 year prior), or community-associated (CA, all
      others). Negative binomial regression models were used to evaluate the adjusted
      rate ratio (aRR) of MRSA in black patients (vs in white patients) controlling for
      age, sex, and temporal trends. Results: During 2005-2014, invasive HO and HACO
      (but not CA) MRSA rates decreased. Despite this, blacks had higher rates for HO
      (aRR, 3.20; 95% confidence interval [CI], 2.35-4.35), HACO (aRR, 3.84; 95% CI,
      2.94-5.01), and CA (aRR, 2.78; 95% CI, 2.30-3.37) MRSA. Limiting the analysis to
      chronic dialysis patients reduced, but did not eliminate, the higher HACO MRSA
      rates among blacks (aRR, 1.83; 95% CI, 1.72-1.96), even though invasive MRSA
      rates among dialysis patients decreased during 2005-2014. These racial
      differences did not change over time. Conclusions: Previous reductions in
      healthcare-associated MRSA infections have not affected racial disparities in
      MRSA rates. Improved understanding of the underlying causes of these differences
      is needed to develop effective prevention interventions that reduce racial
      disparities in MRSA infections.

PMID- 29659729
TI  - T helper 17.1 cells associate with multiple sclerosis disease activity:
      perspectives for early intervention.
AB  - Interleukin-17-expressing CD4+ T helper 17 (Th17) cells are considered as
      critical regulators of multiple sclerosis disease activity. However, depending on
      the species and pro-inflammatory milieu, Th17 cells are functionally
      heterogeneous, consisting of subpopulations that differentially produce
      interleukin-17, interferon-gamma and granulocyte macrophage colony-stimulating
      factor. In the current study, we studied distinct effector phenotypes of human
      Th17 cells and their correlation with disease activity in multiple sclerosis
      patients. T helper memory populations single- and double-positive for C-C
      chemokine receptor 6 (CCR6) and CXC chemokine receptor 3 (CXCR3) were
      functionally assessed in blood and/or cerebrospinal fluid from a total of 59
      patients with clinically isolated syndrome, 35 untreated patients and 24
      natalizumab-treated patients with relapsing-remitting multiple sclerosis, and
      nine patients with end-stage multiple sclerosis. Within the clinically isolated
      syndrome group, 23 patients had a second attack within 1 year and 26 patients did
      not experience subsequent attacks during a follow-up of >5 years. Low frequencies
      of T helper 1 (Th1)-like Th17 (CCR6+CXCR3+), and not Th17 (CCR6+CXCR3-) effector
      memory populations in blood strongly associated with a rapid diagnosis of
      clinically definite multiple sclerosis. In cerebrospinal fluid of clinically
      isolated syndrome and relapsing-remitting multiple sclerosis patients, Th1-like
      Th17 effector memory cells were abundant and showed increased production of
      interferon-gamma and granulocyte macrophage colony-stimulating factor compared to
      paired CCR6+ and CCR6-CD8+ T cell populations and their blood equivalents after
      short-term culturing. Their local enrichment was confirmed ex vivo using
      cerebrospinal fluid and brain single-cell suspensions. Across all pro
      inflammatory T helper cells analysed in relapsing-remitting multiple sclerosis
      blood, Th1-like Th17 subpopulation T helper 17.1 (Th17.1; CCR6+CXCR3+CCR4-)
      expressed the highest very late antigen-4 levels and selectively accumulated in
      natalizumab-treated patients who remained free of clinical relapses. This was not
      found in patients who experienced relapses during natalizumab treatment. The
      enhanced potential of Th17.1 cells to infiltrate the central nervous system was
      supported by their predominance in cerebrospinal fluid of early multiple
      sclerosis patients and their preferential transmigration across human brain
      endothelial layers. These findings reveal a dominant contribution of Th1-like
      Th17 subpopulations, in particular Th17.1 cells, to clinical disease activity and
      provide a strong rationale for more specific and earlier use of T cell-targeted
      therapy in multiple sclerosis.

PMID- 29659730
TI  - An Information-Driven 2-Pathway Characterization of Occipitotemporal and
      Posterior Parietal Visual Object Representations.
AB  - Recent studies have demonstrated the existence of rich visual representations in
      both occipitotemporal cortex (OTC) and posterior parietal cortex (PPC). Using
      fMRI decoding and a bottom-up data-driven approach, we showed that although
      robust object category representations exist in both OTC and PPC, there is an
      information-driven 2-pathway separation among these regions in the
      representational space, with occipitotemporal regions arranging hierarchically
      along 1 pathway and posterior parietal regions along another pathway. We obtained
      10 independent replications of this 2-pathway distinction, accounting for 58-81%
      of the total variance of the region-wise differences in visual representation.
      The separation of the PPC regions from higher occipitotemporal regions was not
      driven by a difference in tolerance to changes in low-level visual features, did
      not rely on the presence of special object categories, and was present whether or
      not object category was task relevant. Our information-driven 2-pathway structure
      differs from the well-known ventral-what and dorsal-where/how characterization of
      posterior brain regions. Here both pathways contain rich nonspatial visual
      representations. The separation we see likely reflects a difference in neural
      coding scheme used by PPC to represent visual information compared with that of
      OTC.

PMID- 29659733
TI  - How the coming of the NHS changed British neurology.

PMID- 29659731
TI  - Reply: ATAD1 encephalopathy and stiff baby syndrome: a recognizable clinical
      presentation.

PMID- 29659732
TI  - Dalbavancin as Primary and Sequential Treatment for Gram-Positive Infective
      Endocarditis: 2-Year Experience at the General Hospital of Vienna.
AB  - The clinical outcomes and safety of dalbavancin as primary and sequential
      treatment of gram-positive bacteremia with infective endocarditis were evaluated
      retrospectively. The clinical success rate was high (92.6%), but in 24 of 27
      patients dalbavancin was used only after clearance of bacteria from the
      bloodstream.

PMID- 29659735
TI  - A Multispecific Investigation of the Metal Effect in Mammalian Odorant Receptors
      for Sulfur-Containing Compounds.
AB  - Metal-coordinating compounds are generally known to have strong smells, a
      phenomenon that can be attributed to the fact that odorant receptors for intense
      smelling compounds, such as those containing sulfur, may be metalloproteins. We
      previously identified a mouse odorant receptor (OR), Olfr1509, that requires
      copper ions for sensitive detection of a series of metal-coordinating odorants,
      including (methylthio)methanethiol (MTMT), a strong-smelling component of male
      mouse urine that attracts female mice. By combining mutagenesis and quantum
      mechanics/molecular mechanics (QM/MM) modeling, we identified candidate binding
      sites in Olfr1509 that may bind to the copper-MTMT complex. However, whether
      there are other receptors utilizing metal ions for ligand-binding and other sites
      important for receptor activation is still unknown. In this study, we describe a
      second mouse OR for MTMT with a copper effect, namely Olfr1019. In an attempt to
      investigate the functional changes of metal-coordinating ORs in multiple species
      and to decipher additional sites involved in the metal effect, we cloned various
      mammalian orthologs of the 2 mouse MTMT receptors, and a third mouse MTMT
      receptor, Olfr15, that does not have a copper effect. We found that the function
      of all 3 MTMT receptors varies greatly among species and that the response to
      MTMT always co-occurred with the copper effect. Furthermore, using ancestral
      reconstruction and QM/MM modeling combined with receptor functional assay, we
      found that the amino acid residue R260 in Olfr1509 and the respective R261 site
      in Olfr1019 may be important for receptor activation.

PMID- 29659734
TI  - Quantitative Analysis of Multi-components by Single Marker and Fingerprint
      Analysis of Achyranthes bidentata Blume.
AB  - A simple and effective method of high performance liquid chromatography (HPLC)
      with diode array detection was established to identify the origin of Achyranthes
      bidentata Blume and evaluate its quality, based on chromatographic fingerprint
      combined with the similarity analysis, hierarchical cluster analysis and the
      quantitative analysis of multi-components by single marker (QAMS). In the
      chromatographic fingerprint, 16 peaks were selected as the common model to
      evaluate the similarities among 18 batches (S1-S18) of A. bidentata Blume samples
      collected from different origins in China. The similarities values for 18 batches
      of samples were more than 0.75, which compared with control fingerprint.
      Furthermore, 18 batches of A. bidentata Blume samples were categorized into two
      groups for quantitative analysis, the quantification of three bioactive
      constituents (beta-ecdysterone, cyasterone and 5-hydroxymethyl furfural) between
      QAMS and external standard method proved the consistency of the two methods, the
      three constituents showed good regression (R > 0.9995) within linear ranges, and
      their recoveries were within the range of 97.6-101.5%. This study demonstrated
      that the quality of A. bidentata Blume can be successfully evaluated by means of
      a combination of HPLC chromatographic fingerprint and QAMS approach.

PMID- 29659736
TI  - ATAD1 encephalopathy and stiff baby syndrome: a recognizable clinical
      presentation.

PMID- 29659737
TI  - Feeding-Related Gut Microbial Composition Associates With Peripheral T-Cell
      Activation and Mucosal Gene Expression in African Infants.
AB  - Background: Exclusive breastfeeding reduces the rate of postnatal human
      immunodeficiency virus (HIV) transmission compared to nonexclusive breastfeeding;
      however, the mechanisms of this protection are unknown. Our study aimed to
      interrogate the mechanisms underlying the protective effect of exclusive
      breastfeeding. Methods: We performed a prospective, longitudinal study of infants
      from a high-HIV-prevalence, low-income setting in South Africa. We evaluated the
      role of any non-breast milk feeds, excluding prescribed medicines on stool
      microbial communities via 16S rRNA gene sequencing, peripheral T-cell activation
      via flow cytometry, and buccal mucosal gene expression via quantitative
      polymerase chain reaction assay. Results: A total of 155 infants were recruited
      at birth with mean gestational age of 38.9 weeks and mean birth weight of 3.2 kg.
      All infants were exclusively breastfed (EBF) at birth, but only 43.5% and 20%
      remained EBF at 6 or 14 weeks of age, respectively. We observed lower stool
      microbial diversity and distinct microbial composition in exclusively breastfed
      infants. These microbial communities, and the relative abundance of key taxa,
      were correlated with peripheral CD4+ T-cell activation, which was lower in EBF
      infants. In the oral mucosa, gene expression of chemokine and chemokine receptors
      involved in recruitment of HIV target cells to tissues, as well as epithelial
      cytoskeletal proteins, was lower in EBF infants. Conclusions: These data suggest
      that nonexclusive breastfeeding alters the gut microbiota, increasing T-cell
      activation and, potentially, mucosal recruitment of HIV target cells. Study
      findings highlight a biologically plausible mechanistic explanation for the
      reduced postnatal HIV transmission observed in EBF infants.

PMID- 29659738
TI  - Disseminated Infection of Encephalitozoon cuniculi Associated With Osteolysis of
      Hip Periprosthetic Tissue.
AB  - Background: Among patients with hip joint endoprosthesis, periprosthetic
      osteolysis is the most common complication following primary arthroplasty, and
      subsequent implant loosening is the leading cause of arthroplasty revision.
      Causes of stability loss, though not always evident, can be mechanical, allergic,
      or infectious (bacterial and fungal agents) in nature. Microsporidia, widespread
      opportunistic fungal pathogens that infect most human tissues, are a potential
      infectious cause of stability loss. Infections caused by Encephalitozoon species
      one of the most common microsporidial pathogens in humans-primarily localize to
      intestinal and respiratory tracts, but can disseminate to tissues throughout the
      body. Methods: We examined 53 immunocompetent patients, 23 after revision and 30
      after primary hip arthroplasty, for infection by Encephalitozoon species.
      Periprosthetic tissue, urine sediments, and stool samples were tested by
      microscopic examination and genus-specific nested polymerase chain reaction
      followed by genotyping. Results: Ten patients had Encephalitozoon-positive
      periprosthetic tissues, 9 (39%) after revision and 1 (3.3%) after primary hip
      arthroplasty. Among the tissue-positive postrevision patients, 7 had a positive
      urine sample and 1 had a positive stool sample. Encephalitozoon cuniculi genotype
      II was identified in 88.8% (16/18) of samples. Two urine samples were positive
      for a novel Encephalitozoon species. Conclusions: Encephalitozoon cuniculi should
      be considered as a cause of osteolysis in hip periprosthetic tissue, leading to a
      loss of implant stability.

PMID- 29659739
TI  - Physical Exercise Improves Aging-Related Changes in Angiotensin, IGF-1, SIRT1,
      SIRT3, and VEGF in the Substantia Nigra.
AB  - Dysregulation of tissue renin-angiotensin system (RAS) is involved in oxidative
      and inflammatory processes observed in major aging-related diseases, including
      neurodegenerative diseases such as Parkinson's disease (PD). Physical exercise
      has beneficial effects against aging-related changes, dopaminergic neuron
      vulnerability, and PD progression. The present study indicates that sedentary
      aged rats have an increase in activity of the nigral angiotensin (Ang) II/Ang
      type 1 receptor (AT1) axis (ie, the pro-oxidative pro-inflammatory arm), and a
      decrease in the activity of the RAS protective arm (ie, Ang II/AT2 and Ang 1
      7/Mas receptor axis) in comparison with young rats. In addition, sedentary aged
      rats showed a decrease in levels of nigral IGF-1, SIRT1, SIRT3, and VEGF.
      Treadmill running induced a significant increase in levels of IGF-1, SIRT1,
      SIRT3, and VEGF, as well as an increase in expression of the protective Ang 1
      7/Mas axis and inhibition of the Ang II/AT1 axis. The exercise-induced increase
      in IGF-1 and sirtuins may mediate the effects of exercise on the nigral RAS.
      However, exercise may induce the increase in VEGF and modulation of RAS activity
      by different pathways. Exercise, via RAS, contributes to inhibition of the pro
      oxidative and proinflammatory state that increase dopaminergic neuron
      vulnerability and risk of PD with aging.

PMID- 29659740
TI  - Cross-Border Transmission of Ebola Virus as the Cause of a Resurgent Outbreak in
      Liberia in April 2016.

PMID- 29659741
TI  - Formin 2 Regulates Lysosomal Degradation of Wnt-Associated beta-Catenin in Neural
      Progenitors.
AB  - Although neural progenitor proliferation along the ventricular zone is regulated
      by beta-catenin through Wnt signaling, the cytoskeletal mechanisms that regulate
      expression and localization of these proteins are not well understood. Our prior
      studies have shown that loss of the actin-binding Filamin A (FlnA) and actin
      nucleating protein Formin 2 (Fmn2) impairs endocytosis of low-density-lipoprotein
      receptor-related protein 6 (Lrp6), thereby disrupting beta-catenin activation,
      resulting in decreased brain size. Here, we report that activated RhoA-GTPase
      disengages Fmn2 N- to C-terminal binding to promote Fmn2 activation and
      redistribution into lysosomal vesicles. Fmn2 colocalizes with beta-catenin in
      lysosomes and promotes its degradation. Further, Fmn2 binds the E3 ligase Smurf2,
      enhances Smurf2-dependent ubiquitination, and degradation of Dishevelled-2
      (Dvl2), thereby initiates beta-catenin degradation. Finally, Fmn2 overexpression
      disrupts neuroepithelial integrity, neuronal migration, and proliferation
      phenotypes in E13 mouse embryos, as seen with loss of Fmn2+FlnA function.
      Conversely, co-expression of Dvl2 with Fmn2 rescues the proliferation defect due
      to Fmn2 overexpression in mouse embryos. These findings suggest that there is a
      homeostatic feedback mechanism in the cytoskeletal-dependent regulation of neural
      proliferation within the cerebral cortex. Upstream, Fmn2 promotes proliferation
      by stabilizing the Lrp6 receptor, leading to beta-catenin activation. Downstream,
      RhoA-activated Fmn2 promotes lysosomal degradation of Dvl2, leading to beta
      catenin degradation.

PMID- 29659742
TI  - Sample Pretreatment Method for Determination of Indicator Polychlorinated
      Biphenyls in Seafood using Ultrasonic Extraction Followed by Dispersive Solid
      Phase Extraction and Gas Chromatography - Electron Capture Detection.
AB  - A simple, rapid and novel method has been developed and validated for the
      determination of seven indicator polychlorinated biphenyls (PCBs) in seafood
      samples by gas chromatography coupled to electron capture detector. Freeze-dried
      samples were done first ultrasonic extraction by n-hexane:methylene
      chloride:acetone (3:1:1, v/v), and then one-step clean-up (dispersive solid-phase
      extraction clean-up) or two-step clean-up (concentrated sulfuric acid
      purification and dispersive solid-phase extraction clean-up) was selected
      according to the lipid contents of the samples, if the lipid content was no more
      than 1%, one-step clean-up was used, otherwise, two-step clean-up was chose. The
      linearity of this method ranged from 1.25 to 100 MUg/L, with regression
      coefficients ranging between 0.9991 and 0.9998. The limits of detection were in
      low ng/g level, ranging between 0.005 and 0.0076 ng/g (wet weight). The
      recoveries of spiked seven PCBs with external calibration method at different
      concentration levels in Pseudosciaena polyactis, Penaeus vannamei and
      Sinonovacula constricta were in the range of 78-105%, 73-110% and 75-107%,
      respectively, and with relative standard deviations of 3.3-5.1%, 3.5-6.3% and 3.4
      5.1% (n = 5), respectively. The performance of the proposed method was also
      compared with traditional soxhlet extraction and column chromatography clean-up
      on the same real seafood samples and comparable efficiencies were obtained. It is
      concluded that this method can be successfully applied for the determination of
      PCBs in different seafood samples.

PMID- 29659743
TI  - Association of biomarker and physiologic indices with mortality in older adults:
      Cardiovascular Health Study.
AB  - Background: A goal of gerontology is discovering aging phenotypes that reflect
      biological aging distinct from disease pathogenesis. Biomarkers strongly and
      independently associated with mortality and which statistically attenuate
      chronologic age could be used to define such a phenotype. We determined the
      association of a Biomarker Index (BI) with mortality and compared it to a
      validated Physiologic Index (PI) in older adults. Methods: The indices were
      constructed in the Cardiovascular Health Study, mean (SD) age 74.5 (5.1) years.
      The BI incorporated circulating levels of new biomarkers, including insulin-like
      growth factor (IGF)-1, IGF binding protein 3, amino-terminal pro-B-type
      natriuretic peptide, dehydroepiandrosterone sulfate, and interleukin-6, and was
      built in test (N=2197) and validation (N=1124) samples. The PI included carotid
      intima-media thickness, pulmonary capacity, brain white matter grade, cystatin-C,
      and fasting glucose. Multivariable Cox proportional hazards models predicting
      death were calculated with 10 years of follow-up. Results: In separate age
      adjusted models, the hazard ratio (HR) for mortality per point of the BI was 1.30
      (95% CI 1.25, 1.34) and the BI attenuated age by 25%. The HR for the PI was 1.28
      (1.24, 1.33) (29% age attenuation). In the same model, the HR for the BI was 1.23
      (1.18, 1.28) and for the PI was 1.22 (1.17, 1.26), and age was attenuated 42.5%.
      Associations persisted after further adjustment. Conclusions: The BI and PI were
      significantly and independently associated with mortality. Both attenuated the
      age effect on mortality substantially. The indices may be feasible phenotypes for
      developing interventions hoping to alter the trajectory of aging.

PMID- 29659744
TI  - Human adipose mesenchymal stem cells overexpressing dual chemotactic gene showed
      enhanced angiogenic capacity in ischaemic hindlimb model.
AB  - Aims: In present study, we sought to characterize the angio-vasculogenic property
      of human adipose mesenchymal stem cells (ASCs) overexpressing dual chemokine GCP
      2 and SDF-1alpha (ASC-G/S) and to determine the therapeutic potential of ASC-G/S
      in the context of experimental ischaemia. Methods and results: We generated ASC
      G/S line and performed flow cytometry, quantitative (q)-PCR, Matrigel tube
      formation, Matrigel plug assays, and in vivo therapeutic assays using hind limb
      ischaemia mouse model. Q-PCR results showed that the representative pro
      angiogenic factors were highly upregulated in ASC-G/S compared with ASCs single
      chemokine overexpressing GCP-2 (ASC-G). In addition, ASC-G/S exhibited high
      expression of endothelium-specific genes shch as vWF and Flk-1 and showed robust
      in vitro micro-vascular formation. ASC-G/S was transplanted into ischaemic mouse
      hind limbs and compared with control groups. ASC-G/S injection prevented limb
      loss and augmented blood perfusion, suggesting that ASC-G/S enhances
      neovascularization in hind limb ischaemia. In addition, transplanted ASC-G/S
      revealed high vasculogenic potential in vivo compared with transplanted ASC-G.
      Conclusion: Our data suggest that ASC-G/S has high therapeutic effects on hind
      limb ischaemia via robust angiogenic and vasculogenic action.

PMID- 29659745
TI  - Reply to Mercuro et al.

PMID- 29659746
TI  - Reply: Visually-sensitive networks in essential tremor: evidence from structural
      and functional imaging.

PMID- 29659748
TI  - Burden, Etiology, and Risk Factors of Respiratory Virus Infections Among
      Symptomatic Preterm Infants in the Tropics: A Retrospective Single-Center Cohort
      Study.
AB  - Background: The burden of respiratory viral infections (RVIs) among preterm
      infants in the first few years of life, especially those living in the tropics
      with year-long transmissions of respiratory viruses, remains unknown. We aimed to
      describe the clinical epidemiology and associated risk factors for RVIs among
      symptomatic preterm infants <=32 weeks up to 2 years of life. Methods: We
      performed a data linkage analysis of clinical and hospital laboratory databases
      for preterm infants born at KK Women's and Children's Hospital, Singapore, from
      2005 to 2015. RVI episodes during initial admission and subsequent hospital
      readmissions were included. Results: Of 1854 infants in the study, 270 (14.5%)
      infants were diagnosed with at least 1 RVI. A total of 285 (85.3%) episodes were
      diagnosed postdischarge, with the highest risk for RVIs being from 3 to 5 months
      of age. The incidence of RVI in this population was 116 per 1000 infant-years and
      respiratory syncytial virus was the main overall causative pathogen. Infants with
      RVIs were more likely to be born at <=27 weeks' gestational age (odds ratio [OR],
      1.7; 95% confidence interval [CI], 1.2-2.3), to have received postnatal steroids
      (OR, 1.5; 95% CI, 1.0-2.1), and to be diagnosed with bronchopulmonary dysplasia
      (OR, 1.7; 95% CI, 1.2-2.4). Conclusions: The burden of RVIs is high in preterm
      infants in the tropics, affecting >1 of 10 infants born at <=32 weeks' gestation
      before 2 years of age. Respiratory syncytial virus was the main causative
      pathogen identified. Risk factors for RVI included extremely low gestational age,
      receipt of postnatal steroids, and bronchopulmonary dysplasia.

PMID- 29659747
TI  - Two Distinct Patterns of Clostridium difficile Diversity Across Europe Indicating
      Contrasting Routes of Spread.
AB  - Background: Rates of Clostridium difficile infection vary widely across Europe,
      as do prevalent ribotypes. The extent of Europe-wide diversity within each
      ribotype, however, is unknown. Methods: Inpatient diarrheal fecal samples
      submitted on a single day in summer and winter (2012-2013) to laboratories in 482
      European hospitals were cultured for C. difficile, and isolates the 10 most
      prevalent ribotypes were whole-genome sequenced. Within each ribotype, country
      based sequence clustering was assessed using the ratio of the median number of
      single-nucleotide polymorphisms between isolates within versus across different
      countries, using permutation tests. Time-scaled Bayesian phylogenies were used to
      reconstruct the historical location of each lineage. Results: Sequenced isolates
      (n = 624) were from 19 countries. Five ribotypes had within-country clustering:
      ribotype 356, only in Italy; ribotype 018, predominantly in Italy; ribotype 176,
      with distinct Czech and German clades; ribotype 001/072, including distinct
      German, Slovakian, and Spanish clades; and ribotype 027, with multiple
      predominantly country-specific clades including in Hungary, Italy, Germany,
      Romania, and Poland. By contrast, we found no within-country clustering for
      ribotypes 078, 015, 002, 014, and 020, consistent with a Europe-wide
      distribution. Fluoroquinolone resistance was significantly more common in within
      country clustered ribotypes (P = .009). Fluoroquinolone-resistant isolates were
      also more tightly clustered geographically with a median (interquartile range) of
      43 (0-213) miles between each isolate and the most closely genetically related
      isolate, versus 421 (204-680) miles in nonresistant pairs (P < .001).
      Conclusions: Two distinct patterns of C. difficile ribotype spread were observed,
      consistent with either predominantly healthcare-associated acquisition or Europe
      wide dissemination via other routes/sources, for example, the food chain.

PMID- 29659749
TI  - A Brief History of Evolving Diagnostics and Therapy for Gonorrhea: Lessons
      Learned.
AB  - Progressively decreasing susceptibility of Neisseria gonorrhoeae to the
      antibiotics recommended for treatment has raised concerns about the public health
      threat of antibiotic resistant gonorrhea. This is not a new process, and the
      organism has reliably developed resistance to all modern antibiotics used for
      treatment since the dawn of the antibiotic era. The history of changing
      recommendations for gonorrhea therapy is complex, however, and has been
      influenced by diagnostic test methods and surveillance. Understanding the impact
      of these influences may provide insights into current approaches to address this
      reemerging public health challenge. We reviewed available methods for gonorrhea
      diagnosis, and public health recommendations for gonorrhea treatment. The
      literature review was supplemented by qualitative interviews with senior
      investigators whose research helped shape gonorrhea management strategies over
      the past 50 years. The process of development of antimicrobial resistance to the
      antibiotics widely used for treatment seems to be inexorable. Many currently
      voiced concerns are similar to those raised in the past. The public health threat
      of increasing antimicrobial resistance by N. gonorrhoeae has been amplified as a
      result of a smaller pipeline introducing new drugs for gonorrhea treatment.
      Improved methods for gonorrhea diagnosis have also repeatedly influenced
      appreciation of the burden of disease caused by N. gonorrhoeae. US Public Health
      Service leadership has also shaped and improved the management of this important
      public health problem.

PMID- 29659750
TI  - Simultaneous Qualitative and Quantitative Study of Main Compounds in Commelina
      communis Linn. by UHPLC-Q-TOF-MS-MS and HPLC-ESI-MS-MS.
AB  - This study reported the identification and determination of the main components
      of Commelina communis Linn. A total of 62 compounds were identified in C.
      communis Linn. extract, which included 29 flavonoids and flavonoid glycosides, 17
      phenolic acids, 4 alkaloids, 1 pyrimidine alkaloids, 3 sterols and 8 fatty acids
      and others by ultra high performance liquid chromatography coupled with hybrid
      triple quadrupole time-of-flight mass spectrometry. Moreover, a specific, simple,
      rapid and sensitive high performance liquid chromatography with tandem mass
      spectrometry method was developed and validated for determination of 13
      components of C. communis Linn., which included orientin, iso-orientin, vitexin,
      isovitexin, rutin, apigenin, protocatechuate, vanillic acid, caffeic acid,
      ferulic acid, luteolin, quercetin and isorhamnetin. All calibration curves showed
      good linearity (r >= 0.9991) within the test range. The intra- and inter-day
      precisions (relative standard deviation%, RSD%) were within 1.04 and 0.92%, and
      the recoveries ranged from 98.64 to 100.8%. These results may contribute to the
      further study and quality control for C. communis Linn.

PMID- 29659751
TI  - A Randomized, Placebo-Controlled Trial of the Quadrivalent Human Papillomavirus
      Vaccine in Human Immunodeficiency Virus-Infected Adults Aged 27 Years or Older:
      AIDS Clinical Trials Group Protocol A5298.
AB  - Background: Adults living with human immunodeficiency virus (HIV) are at
      increased risk for anal and oropharyngeal cancer caused by human papillomavirus
      (HPV). The efficacy of HPV vaccines in this population is unknown. Methods: In
      this phase 3, double-blind, randomized, controlled trial, we assigned HIV
      infected adults aged >=27 years to the quadrivalent HPV (types 6, 11, 16, 18)
      vaccine or placebo (1:1) stratified by sex and presence of anal high-grade
      squamous intraepithelial lesions on biopsy (bHSIL). The primary endpoint was
      vaccine efficacy against incident persistent anal infection with quadrivalent
      vaccine types or single detection at the final visit that were not present at
      baseline. Secondary endpoints included vaccine efficacy for anal bHSIL after week
      52, persistent oral HPV infection. Results: A total of 575 participants were
      randomized. The Data and Safety Monitoring Board stopped the study early due to
      futility. Vaccine efficacy was 22% (95.1% confidence interval [CI], -31%, 53%)
      for prevention of persistent anal infection or single detection at the final
      visit, 0% (95% CI -44%, 31%) for improving bHSIL outcomes and 88% (95.1% CI 2%,
      98%) for preventing persistent oral HPV infection, but was 32% (95.1% CI -80%,
      74%) for 6-month persistent oral HPV infection or single detection at the final
      visit. Conclusions: These results do not support HPV vaccination of HIV-infected
      adults aged >=27 years to prevent new anal HPV infections or to improve anal HSIL
      outcomes. However, our data suggest a role for prevention of oral HPV infections,
      but this finding should be confirmed in future studies. Clinical Trials
      Registration: NCT01461096.

PMID- 29659752
TI  - Performance of Anal Cytology Compared With High-Resolution Anoscopy and Histology
      in Women With Lower Anogenital Tract Neoplasia.
AB  - Background: Information on the performance of anal cytology in women who are high
      risk for human papillomavirus-related lesions and the factors that might
      influence cytology are largely lacking. Methods: Retrospective study including
      all new referrals of women with a previous history of anogenital neoplasia from
      January 2012 to July 2017, with concomitant anal cytology and high-resolution
      anoscopy with or without biopsies. Results: Six hundred and thirty six anal
      cytology samples and 323 biopsies obtained from 278 women were included. Overall
      sensitivity and specificity of "any abnormality" on anal cytology to predict any
      abnormality in histology was 47% (95% confidence interval [CI], 41%-54%) and 84%
      (95% CI, 73%-91%), respectively. For detecting high-grade squamous
      intraepithelial lesions (HSIL)/cancer, sensitivity was 71% (95% CI, 61%-79%) and
      specificity was 73% (95% CI, 66%-79%). There was a poor concordance between
      cytological and histological grades (kappa = 0.147). Cytology had a higher
      sensitivity to predict HSIL/cancer in immunosuppressed vs nonimmunosuppressed
      patients (92% vs 60%, P = .002). The sensitivity for HSIL detection was higher
      when 2 or more quadrants were affected compared with 1 (86% vs 57%, P = .006). A
      previous history of vulvar HSIL/cancer (odds ratio [OR], 1.71, 1.08-2.73; P =
      .023), immunosuppression (OR, 1.88, 1.17-3.03; P = .009), and concomitant genital
      HSIL/cancer (OR, 2.51, 1.47-4.29; P = .001) were risk factors for abnormal
      cytology. Conclusions: Women characteristics can influence the performance of
      anal cytology. The sensitivity for detecting anal HSIL/cancer was higher in those
      immunosuppressed and with more extensive disease.

PMID- 29659753
TI  - Patient and Strain Characteristics Associated With Clostridium difficile
      Transmission and Adverse Outcomes.
AB  - Background: No study has used whole-genome sequencing (WGS) to investigate risk
      factors for Clostridium difficile (CD) transmission between cases, or assessed
      the impact of recent acquisition on patient outcome. Methods: This 20 month
      retrospective cohort study included consecutive cytotoxin-positive diarrheal
      samples, which underwent culture, ribotyping, and WGS (Illumina). Sequenced
      isolates were compared using single nucleotide variants (SNVs). Independent
      predictors of acquisition from another case, onward transmission, 120-day
      recurrence, and 30-day mortality were identified using logistic regression with
      backwards elimination. Results: Of 660 CD cases, 640 (97%) were sequenced, of
      which 567 (89%) shared a ribotype with a prior case, but only 227 (35%) were <=2
      SNVs from a prior case, supporting recent acquisition. Plausible (<2 SNVs) recent
      ward-based acquisition from a symptomatic case was more frequent in certain
      ribotypes; 64% (67/105) for ribotype-027 cases, compared with 11% (6/57) for
      ribotype-078. Independent risk factors (adjusted P < .05) for CD acquisition
      included older age, longer inpatient duration, and ribotype; these factors, and
      male sex, increased onward transmission. Patients with a plausible donor had a
      greater risk of recurrence (adjusted P = .001) and trended towards greater 30-day
      mortality (adjusted P = .06). Ribotype had no additional mortality or recurrence
      impact after adjusting for acquisition (P > .1). Conclusions: Greater
      transmission of certain lineages suggests CD may have different reservoirs and
      modes of transmission. Acquiring CD from a recent case is associated with poorer
      clinical outcomes. Clinical characteristics associated with increased healthcare
      associated CD transmission could be used to target preventative interventions.

PMID- 29659754
TI  - A Randomized Study Evaluating the Effectiveness of Oseltamivir Initiated at the
      Time of Hospital Admission in Adults Hospitalized With Influenza-Associated Lower
      Respiratory Tract Infections.
AB  - Background: Influenza-associated hospitalizations result in high morbidity and
      mortality. We sought to determine if early empiric anti-influenza therapy
      improves outcomes of hospitalized patients with influenza-associated lower
      respiratory tract infections (I-LRTIs). Methods: This was a randomized,
      unblinded, trial of adult patients hospitalized with I-LRTIs in Kentucky during
      2009-2012. Patients were randomized to group A (standard of care) or group B
      (standard of care plus oseltamivir as early as possible but within 24 hours of
      enrollment). The primary outcome was development of clinical failure (composite
      variable including failure to reach clinical improvement within 7 days, transfer
      to intensive care 24 hours after admission, or rehospitalization or death within
      30 days). Intent-to-treat (ITT) (all LRTI) and per-protocol (PP) (I-LRTI)
      analyses were done. Results: A total of 1107 patients were enrolled and included
      in the ITT analysis, 556 in group A and 551 in group B. The median time from
      symptom onset to hospital admission was 5 days (interquartile range, 5) for both
      groups; oseltamivir was initiated median day 6 in group B. There was no
      difference in the development of clinical failure (group A, 25%, and group B,
      24%; P = .561). In the PP analysis, 11 of 45 (24%) patients in group A and 4 of
      29 (14%) patients in group B had clinical failure (P = .414). Conclusions:
      Initiation of oseltamivir more than 5 days after illness onset did not reduce
      clinical failures among hospitalized patients with I- LRTIs. However, we did not
      enroll our projected sample size of I-LRTI. Clinical Trials Registration:
      NCT01248715.

PMID- 29659755
TI  - Mechanical Thrombectomy for Patients With Infective Endocarditis and Ischemic
      Large-Vessel Stroke.

PMID- 29659756
TI  - Six of one is not half a dozen of the other.

PMID- 29659757
TI  - Depression and Anxiety as Risk Factors for Delayed Care-Seeking Behavior in Human
      Immunodeficiency Virus-Infected Individuals in South Africa.
AB  - Background: Facility- and community-based efforts to improve human
      immunodeficiency virus (HIV) testing in sub-Saharan Africa may benefit from
      understanding how mental health influences HIV care-seeking behavior. Methods: We
      conducted a study among adults presenting for HIV testing in the Umlazi township
      of South Africa. Prior to testing, we measured depression using the 9-item
      Patient Health Questionnaire and anxiety using the 7-item Generalized Anxiety
      Disorder scale. We categorized patients as delayed presenters (presenting to
      clinic >3 months after first HIV-positive test), late testers (presenting within
      3 months of diagnosis with a CD4 count <=200 cells per uL), or neither. We used
      multinomial logistic regression adjusting for sociodemographic and behavioral
      characteristics to determine the effects of depression and anxiety on HIV care
      seeking behavior. Results: Among 1482 HIV-infected adults, 59% were female and
      mean age was 33 years. The prevalence of depression in the cohort was 33% and
      anxiety was 9%. In adjusted models, mild to moderate depression was not
      associated with delayed presentation or late testing. HIV-infected adults with
      severe depression had 3.6 greater odds (95% confidence interval [CI], 1.2-10.2)
      of delayed presentation and 2.2 greater odds (95% CI, 1.01-4.8) of late testing
      compared with those without depression. Individuals with generalized anxiety had
      2.3 greater odds (95% CI, 1.3-4.2) of delayed presentation compared with those
      without anxiety. Conclusions: Severe depression was associated with delayed
      presentation and late testing, while anxiety was associated only with delayed
      presentation. Screening for mental health services may improve antiretroviral
      therapy initiation and linkage to care following HIV testing.

PMID- 29659758
TI  - Accelerated Clearance of Infliximab is Associated With Treatment Failure in
      Patients With Corticosteroid-Refractory Acute Ulcerative Colitis.
AB  - Background and Aims: A significant proportion of patients with corticosteroid
      refractory acute ulcerative colitis [UC] fail therapy. We aimed to assess the
      pharmacokinetics [PK] of infliximab [IFX] in patients with corticosteroid
      refractory acute UC and determine the association between induction IFX PK and
      short- and long-term therapy outcome. Methods: A population PK model was
      developed using data from 51 patients with UC [n = 42] and Crohn's disease [n =
      9]. A subset of patients [n = 36] with acute corticosteroid-refractory UC (median
      Mayo score 11 [range 8-12]; 33 of 36 hospitalized; median corticosteroid dose at
      study entry 50mg prednisolone equivalent IV/oral) commencing IFX were studied to
      assess further correlations between PK from the first induction dose and therapy
      outcomes. Serial induction drug levels from the 36 UC patients were collected,
      facilitating population-based PK analysis. IFX and antibodies-to-infliximab
      [ATIs] concentrations were determined using AnsrTM IFX assay [Prometheus Inc.].
      Results: The Week 14 clinical response and Week 54 corticosteroid-free remission
      rates were 78% [28/36] and 53% [19/36], respectively. The estimated effective IFX
      half-life [T1/2] (median [range]) and clearance (median [range]) were 8.42 [3.94
      22.03] days and 0.50 [0.19-1.41] L/day respectively. Longer induction IFX T1/2
      and lower clearance were associated with the Week 14 clinical response [p =
      0.005] and the Week 54 corticosteroid-free remission rates [p = 0.007].
      Conclusions: Accelerated IFX clearance occurs in corticosteroid-refractory acute
      UC and is associated with therapy failure. These data support the use of
      accelerated IFX induction regimens in patients with corticosteroid-refractory
      acute UC failing conventional dosing regimens.

PMID- 29659759
TI  - Community-Acquired Legionella Pneumonia in Human Immunodeficiency Virus-Infected
      Adult Patients: A Matched Case-Control Study.
AB  - We investigate whether the clinical presentations and outcomes of Legionella
      pneumonia in human immunodeficiency virus (HIV)-infected patients were comparable
      to those seen in non-HIV-infected patients (case-control design). HIV-infected
      individuals presented neither a more severe disease nor a worse clinical outcome
      than matched HIV-negative control patients.

PMID- 29659760
TI  - Coxiella burnetii: A Hidden Pathogen in Interstitial Lung Disease?
AB  - We report 7 patients with interstitial lung disease seen at computed tomographic
      scan review. Coxiella burnetii infection was diagnosed in situ in 1 lung biopsy
      specimen. Q fever may be a cofactor of interstitial lung disease, especially in
      endemic areas.

PMID- 29659761
TI  - Reply to Kendall.

PMID- 29659763
TI  - The Distribution and Habitat Affinities of the Invasive Ant Myrmica rubra
      (Hymenoptera: Formicidae) in Southern New England.
AB  - The Eurasian ant Myrmica rubra (L.) (Hymenoptera: Formicidae) was first
      discovered in North America in the early 1900s in Massachusetts. Populations have
      since appeared in at least seven states within the United States and in seven
      Canadian provinces. We conducted a systematic search for the ant across southern
      New England-the states of Connecticut, Massachusetts, and Rhode Island-where M.
      rubra is spreading from multiple loci. The species occurs in two large regions in
      Massachusetts, each spanning approximately 75 km, and in several smaller
      populations in Massachusetts and Rhode Island. No populations were discovered
      anywhere in Connecticut or across large expanses of central Massachusetts and
      northern Rhode Island, despite the presence of apparently favorable habitat. This
      pattern of distribution suggests a combination of long-distance dispersal by
      human transport coupled with slow local spread. Resurveys of sites previously
      known to support M. rubra showed that populations persist for decades. Within
      invaded areas, M. rubra was strongly associated with particular habitats.
      Colonies were most prevalent in freshwater wetlands and in moist forests near
      wetlands and water; they were uncommon in drier forests and were rare in open
      habitats outside of wetlands. The slow rate of spread over the last 110 yr
      suggests that the ants do not easily disperse between patches of suitable
      habitat.

PMID- 29659762
TI  - Activation of sigma20-dependent recombination and horizontal gene transfer in
      Mycoplasma genitalium.
AB  - In the human pathogen Mycoplasma genitalium, homologous recombination is under
      the control of sigma20, an alternative sigma factor that boosts the generation of
      genetic and antigenic diversity in the population. Under laboratory growth
      conditions, sigma20 activation is rare and the factors governing its intermittent
      activity are unknown. Two sigma20-regulated genes, rrlA and rrlB, showed to be
      important for recombination of homologous DNA sequences in this bacterium.
      Herein, we demonstrate that rrlA and rrlB code for two small proteins that
      participate in a feed-forward loop essential for sigma20 function. In addition,
      we identify novel genes regulated by sigma20 and show that several non-coding
      regions, which function as a reservoir for the generation of antigenic diversity,
      are also activated by this alternative sigma factor. Finally, we reveal that M.
      genitalium cells can transfer DNA horizontally by a novel mechanism that requires
      RecA and is facilitated by sigma20 over-expression. This DNA transfer system is
      arguably fundamental for persistence of M. genitalium within the host since it
      could facilitate a rapid dissemination of successful antigenic variants within
      the population. Overall, these findings impose a novel conception of genome
      evolution, genetic variation and survival of M. genitalium within the host.

PMID- 29659764
TI  - Ambulatory Quinolone Prescribing: Moving From Opportunity to Implementation.

PMID- 29659765
TI  - Physiological Response of Pedunculate Oak Trees to Gall-Inducing Cynipidae.
AB  - Gall-inducing Cynipidae (Hymenoptera) manipulate the leaves of their host plants
      and induce local resistance, resulting in a diversity of physiological changes.
      In this study, three gall morphotypes caused by the asexual generation of Cynips
      quercusfolii L., Neuroterus numismalis (Fourc.) and Neuroterus quercusbaccarum L.
      (Hymenoptera: Cynipidae) on pedunculate oaks (Quercus robur L. (Fagales:
      Fagaceae)), were used as a model to examine physiological alterations in galls
      and foliar tissues, compared to non-galled tissues. Our goal was to investigate
      whether plant physiological response to insect feeding on the same host plant
      varies depending on gall-wasp species. In particular, the cytoplasmic membrane
      condition, hydrogen peroxide (H2O2) concentration and changes in antioxidative
      enzyme activities, including guaiacol peroxidase (GPX) and ascorbate peroxidase
      (APX) were examined in this study. All cynipid species increased H2O2 levels in
      the leaves with galls, while the level of H2O2 in galls depended on the species.
      The presence of galls of all species on oak leaves caused an increase of
      electrolyte leakage and lipid peroxidation level. A significant induction of GPX
      activity was observed in the leaves with galls of all species, indicating stress
      induction. Conversely, the decrease in APX activity in both leaves with galls and
      galled tissues exposed to feeding of all cynipid species.

PMID- 29659766
TI  - Food Suitability and Population Dynamics of Lorryia formosa (Acari: Tydeidae).
AB  - Lorryia formosa Cooreman (Acari: Tydeidae) is a species of mite commonly
      associated with citrus in many countries including the United States. A survey
      report in 1957 suggested phytophagous nature, while other studies claimed that L.
      formosa populations are associated with honeydew producing insects and sooty mold
      and it acts as a sanitizing agent. We investigated the effect of various diets on
      the survival and progeny production of L. formosa on excised leaves and the
      survival and potential to cause feeding damage to leaves of potted plants in a
      greenhouse study. A 2-yr field survey of a mandarin orchard was also conducted to
      elucidate the seasonal infestation, damage potential and population structure of
      L. formosa in a natural habitat. Results showed that all L. formosa adults and
      immatures died in less than 14 d on excised leaves, did not survive beyond 7 d on
      potted citrus plants alone, and caused no observable feeding damage to leaves or
      fruit. When sugar water, honeydew, or cottony cushion scale, Icerya purchasi
      Maskell (Hemiptera: Margarodidae), was present, adults and immatures survived the
      duration of the experiments and produced additional generations. The field survey
      showed that all stages of L. formosa were present in a mandarin orchard
      throughout the year and insecticide applications affected but did not eliminate
      mite populations. Fruit generally had a greater percentage infestation of mites
      (44.8 +/- 4.0) than leaves (16.0 +/- 4.7). These studies confirmed that L.
      formosa cannot sustain a population on leaf tissue alone and is nondamaging to
      citrus in California.

PMID- 29659768
TI  - Digital chest drainage is better than traditional chest drainage following
      pulmonary surgery: a meta-analysis.
AB  - In this systematic review with meta-analysis, we sought to determine the current
      strength of evidence for or against digital and traditional chest drainage
      systems following pulmonary surgery with regards to hard clinical end points and
      cost-effectiveness. PubMed, EMBASE and Web of Science were searched from their
      inception to 31 July 2017. The weighted mean difference (WMD) and the risk ratio
      were used for continuous and dichotomous outcomes, respectively, each with 95%
      confidence intervals (CIs). The heterogeneity and risk of bias were also
      assessed. A total of 10 randomized controlled trials enrolling 1268 patients were
      included in this study. Overall, digital chest drainage reduced the duration of
      chest tube placement (WMD -0.72 days; 95% CI -1.03 to -0.40; P < 0.001), length
      of hospital stay (WMD -0.97 days; 95% CI -1.46 to -0.48; P < 0.001), air leak
      duration (WMD -0.95 days; 95% CI -1.51 to 0.39; P < 0.001), and postoperative
      cost (WMD -443.16 euros; 95% CI -747.60 to -138.73; P = 0.004). However, the
      effect differences between the 2 groups were not significant for the duration of
      a prolonged air leak and the percentage of patients discharged home on a device.
      The stability of these studies was strong. No publication bias was detected. It
      may be necessary to use a digital chest drainage system for patients who
      underwent pulmonary surgery to reduce the duration of chest tube placement,
      length of hospital stay and air leak duration.

PMID- 29659769
TI  - Landscape Context Affects Aphid Parasitism by Lysiphlebus testaceipes
      (Hymenoptera: Aphidiinae) in Wheat Fields.
AB  - Winter wheat is Oklahoma's most widely grown crop, and is planted during
      September and October, grows from fall through spring, and is harvested in June.
      Winter wheat fields are typically interspersed in a mosaic of habitats in other
      uses, and we hypothesized that the spatial and temporal composition and
      configuration of landscape elements, which contribute to agroecosystem diversity
      also influence biological control of common aphid pests. The parasitoid
      Lysiphlebus testaceipes (Cresson; Hymenoptera: Aphidiinae) is highly effective at
      reducing aphid populations in wheat in Oklahoma, and though a great deal is known
      about the biology and ecology of L. testaceipes, there are gaps in knowledge that
      limit predicting when and where it will be effective at controlling aphid
      infestations in wheat. Our objective was to determine the influence of landscape
      structure on parasitism of cereal aphids by L. testaceipes in wheat fields early
      in the growing season when aphid and parasitoid colonization occurs and later in
      the growing season when aphid and parasitoid populations are established in wheat
      fields. Seventy fields were studied during the three growing seasons. Significant
      correlations between parasitism by L. testaceipes and landscape variables existed
      for patch density, fractal dimension, Shannon's patch diversity index, percent
      wheat, percent summer crops, and percent wooded land. Correlations between
      parasitism and landscape variables were generally greatest at a 3.2 km radius
      surrounding the wheat field. Correlations between parasitism and landscape
      variables that would be expected to increase with increasing landscape diversity
      were usually positive. Subsequent regression models for L. testaceipes parasitism
      in wheat fields in autumn and spring showed that landscape variables influenced
      parasitism and indicated that parasitism increased with increasing landscape
      diversity. Overall, results indicate that L. testaceipes utilizes multiple
      habitats throughout the year depending on their availability and acceptability,
      and frequently disperses among habitats. Colonization of wheat fields by L.
      testaceipes in autumn appears to be enhanced by proximity to fields of summer
      crops and semi-natural habitats other than grasslands.

PMID- 29659770
TI  - Reply to Ngu et al.

PMID- 29659771
TI  - Infectious Complications After Deployment Trauma: Following Wounded US Military
      Personnel Into Veterans Affairs Care.
AB  - Background: Infectious complications related to deployment trauma significantly
      contribute to the morbidity and mortality of wounded service members. The Trauma
      Infectious Disease Outcomes Study (TIDOS) collects data on US military personnel
      injured in Iraq and Afghanistan in an observational cohort study of infectious
      complications. Patients enrolled in TIDOS may also consent to follow-up through
      the Department of Veterans Affairs (VA). We present data from the first 337 TIDOS
      enrollees to receive VA healthcare. Methods: Data were collected from the
      Department of Defense (DoD) Trauma Registry, TIDOS infectious disease module, DoD
      and VA electronic medical records, and telephone interview. Cox proportional
      hazard analysis was performed to identify predictors of post-discharge infections
      related to deployment trauma. Results: Among the first 337 TIDOS enrollees who
      entered VA healthcare, 111 (33%) had 244 trauma-related infections during their
      initial trauma hospitalization (2.1 infections per 100 person-days). Following
      initial discharge, 127 (38%) enrollees had 239 trauma-related infections (170
      during DoD follow-up and 69 during VA time). Skin and soft-tissue infections and
      osteomyelitis were predominant during and after the initial trauma
      hospitalization. In a multivariate model, a shorter time to development of a new
      infection following discharge was independently associated with injury severity
      score >=10 and occurrence of >=1 inpatient infection during initial trauma
      hospitalization. Conclusions: Incident infections related to deployment trauma
      continue well after initial hospital discharge and into VA healthcare. Overall,
      38% of enrolled patients developed a new trauma-related infection after their
      initial hospital discharge, with 29% occurring after the patient left military
      service.

PMID- 29659772
TI  - Interaction Between Two Leafminer Parasitoids, Halticoptera arduine (Hymenoptera:
      Pteromalidae) and Diglyphus isaea (Hymenoptera: Eulophidae), in the Management of
      Liriomyza huidobrensis (Diptera: Agromyzidae).
AB  - Liriomyza spp., leafminer flies (Mik; Diptera: Agromyzidae), are economically
      important quarantine pests that puncture and mine leaves and fruits of various
      horticultural crops worldwide, affecting yield and trade. Halticoptera arduine
      (Walker; Hymenoptera: Pteromalidae), a key parasitoid from the pests' areas of
      origin in South America, was introduced as a potential alternative management
      strategy. Prior to H. arduine release, its potential interactions with the
      dominant local ectoparasitoid, Diglyphus isaea (Walker; Hymenoptera: Eulophidae),
      were assessed. Halticoptera arduine and D. isaea were released in single,
      sequential and simultaneous combinations on Liriomyza huidobrensis (Blanchard;
      Diptera: Agromyzidae) to evaluate possible effect on the parasitism rate,
      reproduction and host mortality. The combination of both parasitoids did not
      significantly affect the specific parasitism rates of either of them, an
      indication that H. arduine and D. isaea can coexist. Parasitism rates of the
      exotic H. arduine were significantly superior to the indigenous D. isaea in all
      release combinations except when both species were released simultaneously. While
      50 individuals of D. isaea resulted only in 21.23 +/- 2.1% parasitism, 50
      parasitoids composed of 25 H. arduine and 25 D. isaea caused 53.27 +/- 4.99%.
      Both parasitoids further induced significant nonreproductive host mortalities.
      Both parasitoids' F1 progenies sex ratios were female-biased in all parasitoid
      release combinations except in single release of D. isaea with a balanced sex
      ratio. The improvement in D. isaea's sex ratio induced by the presence of H.
      arduine suggests a synergetic effect on D. isaea's reproductive performance. The
      introduction of H. arduine in horticulture production systems may therefore
      improve natural control of Liriomyza leafminers in East Africa.

PMID- 29659774
TI  - Are intestinal worms nature's anti-atherosclerosis vaccine?

PMID- 29659773
TI  - Gut Barrier Dysfunction-A Primary Defect in Twins with Crohn's Disease
      Predominantly Caused by Genetic Predisposition.
AB  - Background and Aims: The aetiology of Crohn's disease is poorly understood. By
      investigating twin pairs discordant for Crohn's disease, we aimed to assess
      whether the dysregulated barrier represents a cause or a consequence of
      inflammation and to evaluate the impact of genetic predisposition on barrier
      function. Methods: Ileal biopsies from 15 twin pairs discordant for Crohn's
      disease [monozygotic n = 9, dizygotic n = 6] and 10 external controls were
      mounted in Ussing chambers to assess paracellular permeability to 51Chromium [Cr]
      EDTA and trancellular passage to non-pathogenic E. coli K-12. Experiments were
      performed with and without provocation with acetylsalicylic acid.
      Immunofluorescence and ELISA were used to quantify the expression level of tight
      junction proteins. Results: Healthy co-twins and affected twins displayed
      increased 51Cr-EDTA permeability at 120 min, both with acetylsalicylic acid [p <
      0.001] and without [p < 0.001] when compared with controls. A significant
      increase in 51Cr-EDTA flux was already seen at 20 min in healthy monozygotic co
      twins compared with controls [p<=0.05] when stratified by zygosity, but not in
      healthy dizygotic co-twins. No difference in E. coli passage was observed between
      groups. Immunofluorescence of the tight junction proteins claudin-5 and
      tricellulin showed lower levels in healthy co-twins [p < 0.05] and affected twins
      [p < 0.05] compared with external controls, while ELISA only showed lower
      tricellulin in Crohn's disease twins [p < 0.05]. Conclusion: Our results suggest
      that barrier dysfunction is a primary defect in Crohn's disease, since changes
      were predominantly seen in healthy monozygotic co-twins. Passage of E. coli seems
      to be a consequence of inflammation, rather than representing a primary defect.

PMID- 29659775
TI  - Ustekinumab Rescue Therapy in a Patient With Chronic Refractory Pouchitis.

PMID- 29659776
TI  - Disseminated Infection of Encephalitozoon cuniculi Associated With Osteolysis of
      Hip Periprosthetic Tissue: Association Versus Causation.

PMID- 29659777
TI  - Number of pregnancies and subsequent phenotype in a cross-sectional cohort of
      women with arrhythmogenic cardiomyopathy.
AB  - Aims: We aimed to assess the relation between number of pregnancies and cardiac
      structure, function, and arrhythmic events in women with arrhythmogenic
      cardiomyopathy (AC). Methods and results: We included female AC patients in a
      cross-sectional study. Number of pregnancies and pregnancy related symptoms were
      recorded. Ventricular arrhythmias were defined as aborted cardiac arrest,
      sustained ventricular tachycardia, or appropriate implantable cardioverter
      defibrillator therapy. Right and left ventricular dimensions and function,
      including strain analyses, were assessed by echocardiography and magnetic
      resonance imaging. We created a new AC severity score to grade the severity of AC
      disease. We included 77 women (age 47 +/- 16, 43 probands and 34 AC mutation
      positive female relatives), 19 +/- 14 years after last pregnancy. Median number
      of pregnancies was 2 (0-4); 19 had no previous pregnancies, 16 had 1 pregnancy,
      30 had 2, and 12 had >=3 pregnancies. Presence of a definite AC diagnosis (P =
      0.36), severity of AC disease (P = 0.53), and arrhythmic events (P = 0.25) did
      not differ between groups of pregnancies. Number of pregnancies was related to
      increased right ventricular outflow tract diameter in single variable analyses
      [odds ratio (OR) 1.76, 95% confidence interval (CI) 1.08-2.87; P = 0.02], but not
      when adjusted for body surface area and age (OR 1.56, 95% CI 0.91-2.66; P =
      0.11). The number of pregnancies was not associated with any other measures of
      cardiac structure and function. Conclusion: Higher number of pregnancies did not
      seem to relate to a worse phenotype in women with AC.

PMID- 29659778
TI  - Impact of diabetes mellitus on the contractile properties of the left and right
      atrial myofilaments.
AB  - OBJECTIVES: The incidence of diabetes mellitus in patients with ischaemic
      cardiomyopathy is increasing. To evaluate the impact of diabetes mellitus on
      contractility, we examined the calcium-induced force in left and right atrial
      myofilaments of patients with and without diabetes. METHODS: We included 149
      patients (106 without diabetes, 43 with diabetes), scheduled for elective
      coronary artery bypass grafting from August 2016 to June 2017. The left and right
      atria were excised and prepared for skinned fibre measurements (pCa-force curve).
      The unit for the force measurements is Millinewton (mN). Comprehensive
      demographic data as well as echocardiographic findings of the patients were
      collected. RESULTS: We observed a significant decrease of left atrial force
      values in patients with diabetes, averaged over all calcium concentrations
      (patients with diabetes 0.50 +/- 0.19 mN vs 0.68 +/- 0.23 mN in patients without
      diabetes, P = 0.002) as well as in right atrial fibres (patients with diabetes
      0.35 +/- 0.17 mN vs 0.47 +/- 0.21 mN in patients without diabetes, P = 0.005).
      There was a significant influence of repeated measurements (of the calcium
      concentrations) on force in left atrial myofilaments (P < 0.001). There was also
      a significant impact of diabetes on the force values of the different calcium
      concentrations in left atrial myofilaments (P 0.002). In right atrial
      myofilaments we also found a significant influence of repeated measurements (of
      the calcium concentrations) on force (P < 0.001). Additionally the impact of
      diabetes on the force values was significant (P = 0.005). CONCLUSIONS: We
      demonstrated that diabetes mellitus has a significantly negative impact on
      calcium-induced force development in left and right atrial myofilaments.

PMID- 29659781
TI  - Intraoperative analgesic regimens may affect postoperative pain: single-port
      versus multi-port video-assisted thoracic surgery.

PMID- 29659780
TI  - Health Outcomes for Clients of Needle and Syringe Programs in Prisons.
AB  - High levels of drug dependence have been observed in the prison population
      globally, and the sharing of injecting drug equipment in prisons has contributed
      to higher prevalence of bloodborne diseases in prisoners than in the general
      population. Few prison needle and syringe programs (PNSPs) exist. We conducted a
      systematic review to assess evidence regarding health outcomes of PNSPs. We
      searched peer-reviewed databases for data relating to needle and syringe programs
      in prisons. The search methodology was conducted in accordance with accepted
      guidelines. Five studies met review inclusion criteria, and all presented
      evidence associating PNSPs with one or more health benefits, but the strength of
      the evidence was low. The outcomes for which the studies collectively
      demonstrated the strongest evidence were prevention of human immunodeficiency
      virus and viral hepatitis. Few negative consequences from PNSPs were observed,
      consistent with previous evidence assessments. More research is needed on PNSP
      effectiveness, and innovative study designs are needed to overcome methodological
      limitations of previous research. Until stronger evidence becomes available,
      policymakers are urged to recognize that not implementing PNSPs has the potential
      to cause considerable harm, in light of what is currently known about the risks
      and benefits of needle and syringe programs and PNSPs and about the high
      prevalence of human immunodeficiency virus and viral hepatitis in prisons.

PMID- 29659782
TI  - Right ventricular outflow tract reconstruction using a polytetrafluoroethylene
      conduit in Ross patients.
AB  - OBJECTIVES: The type of conduit used for right ventricular outflow tract (RVOT)
      reconstruction during the Ross procedure remains problematic because of the
      limited availability of pulmonary allografts and the unsatisfactory long-term
      results associated with the use of xenografts. Polytetrafluoroethylene (PTFE)
      conduits have been proposed as an alternative. This study evaluated the results
      of RVOT reconstruction using a PTFE conduit during the Ross procedure. METHODS:
      Between 2007 and 2015, 28 patients underwent RVOT reconstruction using PTFE
      conduits. The mean age of the patients was 35.9 +/- 18.1 (range 4-58) years. The
      total root replacement technique was used in all patients. The mean PTFE conduit
      size was 25.3 +/- 2.3 mm. RESULTS: The early mortality rate was 3.6% (1 patient).
      The mean follow-up duration was 48.5 +/- 31.2 months; there were no late deaths.
      The transprosthetic gradients increased significantly over time. The conduit size
      was the only independent predictor of peak RVOT gradient progression (P = 0.02).
      None of the patients demonstrated significant RVOT regurgitation. One patient
      required an RVOT reoperation. CONCLUSIONS: The PTFE conduit demonstrates
      acceptable haemodynamic results at the mid-term follow-up and could be considered
      as an alternative substitute for RVOT reconstruction during the Ross procedure.

PMID- 29659783
TI  - Managed Fire Frequency Significantly Influences the Litter Arthropod Community in
      Longleaf Pine Flatwoods.
AB  - Frequent prescribed burns are essential to pine forest restoration and
      management. Research studies have assessed effects of prescribed fire and burn
      frequency on plants and vertebrates, but impacts of fire on terrestrial
      invertebrate communities are still poorly understood. This case study
      investigated effects of burning frequency on species richness and community
      composition of social insects (ants, Hymenoptera: Formicidae and termites,
      Blattodea: Isoptera) in fire-managed Southern longleaf pine flatwoods in central
      Florida. Community response to different fire frequencies was assessed: burned
      annually, every 2 yr, or every 3 yr, 30 yr unburned and 75 yr unburned. Richness
      was similar across all treatments, but ant community composition and species
      density significantly differed between frequently burned (1, 2, and 3 yr) and
      long-unburned (30 and 75 yr) treatments. Long-unburned treatments had higher ant
      abundance, but the species present were less characteristic of open canopy
      longleaf pine habitat than ants in frequently burned treatments. The annual burn
      treatment differed from 2-yr burn in species density, but to a lesser degree.
      Exotic species abundance was highest in frequently burned sites; only native
      species were detected in the 75-yr unburned plot. The red imported fire ant,
      Solenopsis invicta Buren (Hymenoptera: Formicidae), was detected in all regularly
      burned plots but not in long-unburned sites. Frequent burning at this site
      increased habitat suitability for ant species adapted to the sunny, open canopy,
      and diverse niches characteristic of longleaf pine forest; however, regular fire
      disturbance also increased the likelihood of exotic ant species establishment.

PMID- 29659784
TI  - Left atrial geometry and outcome of atrial fibrillation ablation: results from
      the multicentre LAGO-AF study.
AB  - Aims: Left atrial (LA) remodelling is a key determinant of atrial fibrillation
      (AF) ablation outcome. Optimal methods to assess this process are scarce. LA
      sphericity is a shape-based parameter shown to be independently associated to
      procedural success. In a multicentre study, we aimed to test the feasibility of
      assessing LA sphericity and evaluate its capability to predict procedural
      outcomes. Methods and results: This study included consecutive patients
      undergoing first AF ablation during 2013. A 3D model of the LA chamber, excluding
      pulmonary veins and LA appendage, was used to quantify LA volume (LAV) and LA
      sphericity (>=82.1% was considered spherical LA). In total, 243 patients were
      included across 9 centres (71% men, aged 56 +/- 10 years, 44% with hypertension
      and 76% CHA2DS2-VASc <= 1). Most patients had paroxysmal AF (66%) and underwent
      radiofrequency ablation (60%). Mean LA diameter (LAD), LAV, and LA sphericity
      were 42 +/- 6 mm, 100 +/- 33 mL, and 82.6 +/- 3.5%, respectively. Adjusted Cox
      models identified paroxysmal AF [hazard ratio (HR 0.54, P = 0.032)] and LA
      sphericity (HR 1.87, P = 0.035) as independent predictors for AF recurrence. A
      combined clinical-imaging score [Left Atrial Geometry and Outcome (LAGO)]
      including five items (AF phenotype, structural heart disease, CHA2DS2-VASc <= 1,
      LAD, and LA sphericity) classified patients at low (<=2 points) and high risk
      (>=3 points) of procedural failure (35% vs. 82% recurrence at 3-year follow-up,
      respectively; HR 3.10, P < 0.001). Conclusion: In this multicentre, real-life
      cohort, LA sphericity and AF phenotype were the strongest predictors of AF
      ablation outcome after adjustment for covariates. The LAGO score was easy to
      implement, identified high risk of procedural failure, and could help select
      optimal candidates. Clinical Trial Registration Information: NCT02373982
      (http://clinicaltrials.gov/ct2/show/NCT02373982).

PMID- 29659786
TI  - Impact of Pregnancy and Lactation on the Long-Term Regulation of Energy Balance
      in Female Mice.
AB  - During pregnancy and lactation, the maternal body undergoes many changes in the
      regulation of appetite, body weight, and glucose homeostasis to deal with the
      metabolic demands of the growing fetus and subsequent demands of providing milk
      for offspring. The aim of the current study was to investigate the consequences
      of one reproductive cycle of pregnancy and lactation on the long-term regulation
      of energy homeostasis. After weaning of pups, reproductively experienced (RE)
      mice maintained a higher body weight compared with age-matched control mice.
      Although there was no difference in daily food intake or the feeding response to
      exogenous leptin administration, RE mice were less active than age-matched
      control mice as measured by average daily x + y beam breaks or average daily
      ambulatory distance. RE and age-matched controls were also subjected to either a
      high-fat diet or control diet for 6 weeks to determine if experiencing a major
      challenge to energy homeostasis such as pregnancy and lactation leads to
      increased susceptibility to a second challenge to this system. Although both RE
      and control mice gained a similar amount of body weight on the high-fat diet,
      only the RE mice had impaired glucose tolerance when consuming the high-fat diet,
      thus demonstrating an increased susceptibility to the negative consequences of a
      high-fat diet after pregnancy and lactation. Overall, these data indicate that
      pregnancy and lactation have long-term consequences on energy homeostasis in
      mothers.

PMID- 29659785
TI  - Glucocorticoid-Induced Metabolic Disturbances Are Exacerbated in Obese Male Mice.
AB  - The purpose of this study was to determine the effects of glucocorticoid-induced
      metabolic dysfunction in the presence of diet-induced obesity. C57BL/6J adult
      male lean and diet-induced obese mice were given dexamethasone, and levels of
      hepatic steatosis, insulin resistance, and lipolysis were determined. Obese mice
      given dexamethasone had significant, synergistic effects on fasting glucose,
      insulin resistance, and markers of lipolysis, as well as hepatic steatosis. This
      was associated with synergistic transactivation of the lipolytic enzyme adipose
      triglyceride lipase. The combination of chronically elevated glucocorticoids and
      obesity leads to exacerbations in metabolic dysfunction. Our findings suggest
      lipolysis may be a key player in glucocorticoid-induced insulin resistance and
      fatty liver in individuals with obesity.

PMID- 29659787
TI  - Large dissecting intramural haematoma of the oesophagus and stomach and major
      gastro-oesophageal bleeding after transoesophageal echocardiography during
      transcatheter aortic valve replacement procedures.

PMID- 29659788
TI  - The Burden and Benefits of Caregiving: A Latent Class Analysis.
AB  - Background and Objectives: Informal caregiving to older adults is a key part of
      the U.S. long-term care system. Caregivers' experiences consist of burden and
      benefits, but traditional analytic approaches typically consider dimensions
      independently, or cannot account for burden and benefit levels and combinations
      that co-occur. This study explores how benefits and burden simultaneously shape
      experiences of caregiving to older adults, and factors associated with experience
      types. Research Design and Methods: 2015 National Health and Aging Trends Study
      (NHATS) and National Study of Caregiving (NSOC) data were linked to obtain
      reports from caregivers and recipients. Latent class and regression analysis were
      conducted on a nationally representative sample of U.S. informal caregivers to
      older persons. Results: Five distinguishable caregiving experiences types and
      their population prevalence were identified. Subjective burden and benefits level
      and combination uniquely characterize each group. Primary stressors (recipient
      depression, medical diagnoses), primary appraisal (activities of daily living,
      instrumental activities of daily living, medical task assistance, hours
      caregiving), and background/contextual factors (caregiver age, race, relationship
      to recipient, mental health, coresidence, long-term caregiving) are associated
      with experience types. Discussion and Implications: Findings highlight
      caregivers' experience multiplicity and ambivalence, and identify groups that may
      benefit most from support services. In cases where it is not possible to reduce
      burden, assistance programs may focus on increasing the benefits perceptions.

PMID- 29659789
TI  - Bipolar disorder in primary care: a qualitative study of clinician and patient
      experiences with diagnosis and treatment.
AB  - Objective: To understand primary care patients' and clinicians' experiences with
      diagnosis and treatment of patients with bipolar disorder in primary care.
      Methods: We conducted a qualitative study using thematic content analysis of
      individual interviews with nine primary care clinicians and six patients from
      Federally Qualified Health Centers to understand their experiences with the
      diagnosis and treatment of bipolar disorder. Results: Themes of bipolar disorder
      detection, referral to specialty mental health care and medication treatment
      emerged from individual interviews with primary care patients and clinicians.
      Clinicians and patients faced challenges deciding to continue with care in
      primary care that is easier to access, but less intensive, than specialty care
      that can be harder to access but at times of higher quality. Conclusions:
      Potential next steps in research include identifying ways to support primary care
      clinicians in detection of patients with bipolar disorder, and strategies to
      support treatment of patients in primary care with easier access to specialty
      care including consultation in primary care or co-management with specialty care.

PMID- 29659791
TI  - Human Placental Growth Hormone Variant in Pathological Pregnancies.
AB  - Growth hormone (GH), an endocrine hormone, primarily secreted from the anterior
      pituitary, stimulates growth, cell reproduction, and regeneration and is a major
      regulator of postnatal growth. Humans have two GH genes that encode two versions
      of GH proteins: a pituitary version (GH-N/GH1) and a placental GH-variant (GH
      V/GH2), which are expressed in the syncytiotrophoblast and extravillous
      trophoblast cells of the placenta. During pregnancy, GH-V replaces GH-N in the
      maternal circulation at mid-late gestation as the major circulating form of GH.
      This remarkable change in spatial and temporal GH secretion patterns is proposed
      to play a role in mediating maternal adaptations to pregnancy. GH-V is associated
      with fetal growth, and its circulating concentrations have been investigated
      across a range of pregnancy complications. However, progress in this area has
      been hindered by a lack of readily accessible and reliable assays for measurement
      of GH-V. This review will discuss the potential roles of GH-V in normal and
      pathological pregnancies and will touch on the assays used to quantify this
      hormone.

PMID- 29659790
TI  - Ratio of transmitral early filling velocity to early diastolic strain rate
      predicts long-term risk of cardiovascular morbidity and mortality in the general
      population.
AB  - Aims: It has previously been demonstrated that the ratio of early mitral inflow
      velocity to global diastolic strain rate (E/e'sr) is a significant predictor of
      cardiac events in specific patient populations. The utility of this measurement
      to predict cardiovascular events in a general population has not been evaluated.
      Methods and results: A total of 1238 participants in a general population study
      underwent a health examination including echocardiography where global
      longitudinal strain (GLS) and E/e'sr were determined. The primary endpoint was
      the composite of incident heart failure (HF), acute myocardial infarction (AMI)
      or cardiovascular death (CVD). During follow-up (median 11 years), 140 (11.3%)
      participants reached the composite endpoint. E/e'sr was associated with adverse
      outcome [HR 1.17 95% CI (1.13-1.21); P < 0.001, per 10 cm increase]. After
      multivariable adjustment for echocardiographic and clinical parameters, E/e'sr
      remained an independent predictor of the composite endpoint [HR 1.08, 95% CI
      (1.02-1.13); P = 0.003] as opposed to E/e' [HR 1.03, 95% CI (0.99-1.06); P = 0.11
      per 1 unit increase]. Global longitudinal strain modified the relationship
      between E/e'sr and outcome (P for interaction = 0.015). E/e'sr was a stronger
      predictor in participants with good systolic function as determined by GLS (GLS >
      18%) after multivariable adjustment, when compared to participants with reduced
      systolic function (GLS < 18%) [HR 1.28 95% CI (1.06-1.54); P = 0.011, and HR 1.08
      95% CI (1.02-1.14); P = 0.012, respectively). E/e'sr provided incremental
      information [Harrell's C-index: 0.839 (0.81-0.87) vs. 0.844 (0.82-0.87); P =
      0.045] beyond the SCORE risk chart. Conclusion: In the general population, E/e'sr
      provides independent and incremental prognostic information regarding
      cardiovascular morbidity and mortality. Additionally, E/e'sr is a stronger
      predictor of cardiac events than E/e'.

PMID- 29659792
TI  - Tracking the NGS revolution: managing life science research on shared high
      performance computing clusters.
AB  - Background: Next-generation sequencing (NGS) has transformed the life sciences,
      and many research groups are newly dependent upon computer clusters to store and
      analyze large datasets. This creates challenges for e-infrastructures accustomed
      to hosting computationally mature research in other sciences. Using data gathered
      from our own clusters at UPPMAX computing center at Uppsala University, Sweden,
      where core hour usage of ~800 NGS and ~200 non-NGS projects is now similar, we
      compare and contrast the growth, administrative burden, and cluster usage of NGS
      projects with projects from other sciences. Results: The number of NGS projects
      has grown rapidly since 2010, with growth driven by entry of new research groups.
      Storage used by NGS projects has grown more rapidly since 2013 and is now limited
      by disk capacity. NGS users submit nearly twice as many support tickets per user,
      and 11 more tools are installed each month for NGS projects than for non-NGS
      projects. We developed usage and efficiency metrics and show that computing jobs
      for NGS projects use more RAM than non-NGS projects, are more variable in core
      usage, and rarely span multiple nodes. NGS jobs use booked resources less
      efficiently for a variety of reasons. Active monitoring can improve this
      somewhat. Conclusions: Hosting NGS projects imposes a large administrative burden
      at UPPMAX due to large numbers of inexperienced users and diverse and rapidly
      evolving research areas. We provide a set of recommendations for e
      infrastructures that host NGS research projects. We provide anonymized versions
      of our storage, job, and efficiency databases.

PMID- 29659793
TI  - Good practices and challenges in addressing poliomyelitis and measles in the
      European Union.
AB  - Background: All European Union (EU) and European Economic Area (EEA) Member
      States have pledged to ensure political commitment towards sustaining the
      region's poliomyelitis-free status and eliminating measles. However, there remain
      significant gaps between policy and practice in many countries. This article
      reports on an assessment conducted for the European Commission that aimed to
      support improvements in preparedness and response to poliomyelitis and measles in
      Europe. Methods: A documentary review was complemented by qualitative interviews
      with professionals working in International and EU agencies, and in at-risk or
      recently affected EU/EEA Member States (six each for poliomyelitis and measles).
      Twenty-six interviews were conducted on poliomyelitis and 24 on measles; the data
      were subjected to thematic analysis. Preliminary findings were then discussed at
      a Consensus Workshop with 22 of the interviewees and eight other experts.
      Results: Generic or disease-specific plans exist in the participating countries
      and cross-border communications during outbreaks were generally reported as
      satisfactory. However, surveillance systems are of uneven quality, and clinical
      expertise for the two diseases is limited by a lack of experience. Serious
      breaches of protocol have recently been reported from companies producing
      poliomyelitis vaccines, and vaccine coverage rates for both diseases were also
      sub-optimal. A set of suggested good practices to address these and other
      challenges is presented. Conclusions: Poliomyelitis and measles should be brought
      fully onto the policy agendas of all EU/EEA Member States, and adequate resources
      provided to address them. Each country must abide by the relevant commitments
      that they have already made.

PMID- 29659794
TI  - Understanding medical overuse: the case of problematic polypharmacy and the
      potential of ethnography.

PMID- 29659795
TI  - Managing uncertainty: a qualitative study of GPs' views on the diagnosis and
      immediate management of transient ischaemic attack and the potential of a
      diagnostic tool.
AB  - Background: Most patients with transient ischaemic attack (TIA) present to their
      GP. Early identification and treatment reduces the risk of subsequent stroke and
      consequent disability and mortality. Objective: To explore GPs' views on the
      diagnosis and immediate management of suspected TIA, and the potential utility of
      a diagnostic tool. Methods: This is a qualitative interview study based in
      Leicestershire, UK. A purposive sample of 10 GPs participated in 30-minute semi
      structured telephone interviews. Data were analysed thematically. Results: GPs
      reported that TIA was more likely to be suspected when patients were more obvious
      candidates for TIA based on their history, characteristics and symptom
      presentation. Referrals were in part a strategy to manage risk under conditions
      of uncertainty and to seek reassurance. GPs valued using a TIA risk
      stratification tool but felt this did not inform their diagnostic decision
      making. A diagnostic tool for TIA in primary care was seen to have potential to
      improve the decision-making process about diagnosis and management and enhance
      confidence of GPs, particularly in ruling out TIAs. GPs saw benefits of using
      hard thresholds, but remained concerned about missing TIAs and saw a tool as an
      adjunct to clinical judgement. Conclusions: GPs weigh up the likelihood of TIA in
      the context of assessments of candidacy and diverse, often vague, symptoms. A
      diagnostic tool could support GPs in this process and help reduce reliance on
      referrals to TIA clinics for reassurance, provided the tool was designed to
      support decision making in cases of less 'typical' presentations.

PMID- 29659796
TI  - Dissemination of multi-resistant Gram-negative bacteria into German wastewater
      and surface waters.
AB  - Carbapenem antibiotics constitute the mainstay therapy of nosocomial infections
      with extended spectrum beta-lactamase producing Gram-negative bacteria; however,
      resistance against these compounds is increasing. This study was designed to
      demonstrate that carbapenemase-producing bacteria are disseminated from hospitals
      into the environment. To this end, resistant bacteria were isolated from a
      clinical/urban and from a rural catchment system in Germany in 2016/17. The study
      followed the dissemination of resistant bacteria from the wastewater through the
      wastewater treatment plant (WWTP) into the receiving surface waters. The bacteria
      were cultivated on selective agar and characterized by antibiotic testing, real
      time PCR targeting carbapenemase genes and typing. Bacteria with resistance to
      third generation cephalosporins were isolated from all sample sites. 134 isolates
      harboring carbapenemase genes encoding VIM, NDM and OXA-48 and 26 XDR
      (extensively drug-resistant) strains with susceptibility to only one or two
      antibiotics were isolated from the clinical/urban system. The rural system
      yielded eight carbapenemase producers and no XDR strains. In conclusion, clinical
      wastewaters were charged with a high proportion of multidrug resistant bacteria.
      Although most of these bacteria were eliminated during wastewater treatment,
      dissemination into surface waters is possible as single carbapenemase producers
      were still present in the effluent of the WWTP.

PMID- 29659797
TI  - Apixaban compared to heparin/vitamin K antagonist in patients with atrial
      fibrillation scheduled for cardioversion: the EMANATE trial.
AB  - Aim: The primary objective was to compare apixaban to heparin/vitamin K
      antagonist (VKA) in patients with atrial fibrillation (AF) and <=48 h
      anticoagulation prior to randomization undergoing cardioversion. Methods: One
      thousand five hundred patients were randomized. The apixaban dose of 5 mg b.i.d.
      was reduced to 2.5 mg b.i.d. in patients with two of the following: age >= 80
      years, weight <= 60 kg, or serum creatinine >= 133 umol/L. To expedite
      cardioversion, at the discretion of the investigator, imaging and/or a loading
      dose of 10 mg (down-titrated to 5 mg) was allowed. The endpoints for efficacy
      were stroke, systemic embolism (SE), and death. The endpoints for safety were
      major bleeding and clinically relevant non-major (CRNM) bleeding. Results: There
      were 1038 active and 300 spontaneous cardioversions; 162 patients were not
      cardioverted. Imaging was performed in 855 patients, and 342 received a loading
      dose of apixaban. Comparing apixaban to heparin/VKA in the full analysis set,
      there were 0/753 vs. 6/747 strokes [relative risk (RR) 0; 95% confidence interval
      (95% CI) 0-0.64; nominal P = 0.015], no SE, and 2 vs. 1 deaths (RR 1.98; 95% CI
      0.19-54.00; nominal P > 0.999). In the safety population, there were 3/735 vs.
      6/721 major (RR 0.49; 95% CI 0.10-2.07; nominal P = 0.338) and 11 vs. 13 CRNM
      bleeding events (RR 0.83; 95% CI 0.34-1.89; nominal P = 0.685). On imaging, 60/61
      with thrombi continued randomized treatment; all (61) were without outcome
      events. Conclusions: Rates of strokes, systemic emboli, deaths, and bleeds were
      low for both apixaban and heparin/VKA treated AF patients undergoing
      cardioversion. Clinical Trials.gov number: NCT02100228.

PMID- 29659798
TI  - Can certain infections protect against atherosclerosis?

PMID- 29659799
TI  - Exposure of Escherichia coli to human hepcidin results in differential expression
      of genes associated with iron homeostasis and oxidative stress.
AB  - Hepcidin belongs to the antimicrobial peptide family but has weak activity with
      regards to bacterial killing. The regulatory function of hepcidin in humans
      serves to maintain an iron-restricted environment that limits the growth of
      pathogens; this study explored whether hepcidin affected bacterial iron
      homeostasis and oxidative stress using the model organism Escherichia coli. Using
      the Miller assay it was determined that under low iron availability exposure to
      sub-inhibitory doses of hepcidin (4-12MUM) led to 2-fold and 4-fold increases in
      the expression of ftnA and bfd, respectively (P < 0.05), in both a wild type (WT)
      and Deltafur (ferric uptake regulator) background. Quantitative real-time PCR
      analysis of oxyR and sodA, treated with 4 or 8 MUM of hepcidin showed that
      expression of these genes was significantly (P < 0.05) increased, whereas
      expression of lexA was unchanged, indicating that hepcidin likely mediated
      oxidative stress but did not induce DNA damage.

PMID- 29659800
TI  - Activity Patterns and Health Outcomes in Later Life: The Role of Nature of
      Engagement.
AB  - Background and Objectives: The health benefit of activity participation at older
      ages is documented in the current literature. Many studies, however, only
      explored the health benefits of engaging in a few activities and did not examine
      mechanisms connecting activity participation to health. We investigated the
      pathway between activity and health by testing the mediation role of the nature
      of engagement (physical, cognitive, and social) on physical, mental, and
      cognitive health of older adults. Research Design and Methods: We analyzed data
      of 6,044 older adults from the 2010 and 2012 Health and Retirement Study linked
      with 2011 Consumption and Activity Mail Survey. We used latent class analysis to
      identify the patterns of participating in 33 activities as well as patterns of
      nature of engagement, and examined how these patterns were associated with
      cognition, depressive symptoms, and self-rated health in later life. Results:
      Meaningful patterns of activity (high, medium, low, passive leisure, and working)
      and the nature of activity engagement (full, partial, and minimal) were
      identified. High and working groups, compared to the passive leisure group,
      showed better health and cognition outcomes. The nature of engagement mediated
      the relationship between activity patterns and health, especially for older
      adults who were either full or partially engaged. Discussion and Implications:
      The nature of engagement may play a more important role than the activity itself
      in relation to health. Identifying the heterogeneity in activity engagement in
      later life is critical for tailoring interventions and designing programs that
      can improve the health of older adults.

PMID- 29659801
TI  - Long-term performance of homografts versus stented bioprosthetic valves in the
      pulmonary position in patients aged 10-20 years.
AB  - OBJECTIVES: We aimed to compare the long-term performance of pulmonary homografts
      and stented bioprosthetic valves in the pulmonary position in patients aged 10-20
      years. METHODS: Between January 1995 and December 2015, 188 patients aged 10-20
      years undergoing pulmonary valve replacement were identified retrospectively from
      hospital databases in both congenital cardiac centres in Brisbane. Valve
      performance was evaluated using previously described standard criteria.
      Propensity score matching was used to balance the 2 treatment groups. RESULTS:
      Freedom from structural valve degeneration in homografts (n = 131) was 97%, 92%
      and 85% at 3, 5 and 10 years, respectively, and 91% and 53% at 3 and 5 years,
      respectively, in the bioprosthesis group (n = 57). Freedom from reintervention in
      homografts was 96%, 93% and 88% at 3, 5 and 10 years, respectively, and 93% and
      68% at 3 and 5 years, respectively, in the bioprosthesis group. The unadjusted
      Cox regression analysis demonstrated that a bioprosthesis was at 5.64 times the
      risk of structural valve degeneration and 3.89 times the risk of reintervention.
      The Cox regression analysis performed on the propensity matched sample (45 pairs
      of patients) revealed that a bioprosthesis was at almost 10 times the risk of
      experiencing structural valve degeneration [hazard ratio (HR) = 9.18] and at more
      than 8 times the risk of undergoing a reintervention (HR = 8.34). CONCLUSIONS: In
      our patient population, pulmonary homografts outperformed stented bioprosthetic
      valves within 5 years when implanted in the pulmonary position in patients aged
      10-20 years. We recommend the use of a pulmonary homograft for pulmonary valve
      replacement in this age group in patients undergoing surgery for congenital heart
      disease.

PMID- 29659802
TI  - Cancer incidence in patients with a high normal platelet count: a cohort study
      using primary care data.
AB  - Background: A platelet count >400 * 109/l (i.e. thrombocytosis) is a recently
      discovered risk marker of cancer. The risk of undiagnosed cancer in patients with
      thrombocytosis is 11.6% for men and 6.2% for women, well above the 3% risk
      threshold set by National Institute for Health and Care Excellence (NICE) for
      cancer investigation. Patients with a platelet count at the upper end of the
      normal range (325-400 * 109/l) could be at increased risk of undiagnosed
      malignancy. Objective: To quantify the risk of an undiagnosed cancer in patients
      with a platelet count at the upper end of the normal range. Methods: A primary
      care-based cohort study using Clinical Practice Research Datalink (CPRD) data
      from 2000 to 2013. The study sample comprised 2704 individuals stratified by
      platelet count: 325-349 * 109/l; 350-374 * 109/l; 375-399 * 109/l. Incident
      cancer diagnoses in the year following that platelet count were obtained from
      patient records. Results: Cancer incidence rose with increasing platelet count:
      2.6% [95% confidence interval (CI) 1.9 to 3.6] in subjects with a count of 325
      349 * 109/l, 3.7% (95% CI 2.5 to 5.3) in subjects with a count of 350-374 * 109/l
      and 5.1% (95% CI 3.4 to 7.5) in those with a count of 375-399 * 109/l. Colorectal
      cancer was most commonly diagnosed in all three groups. Cancer incidence was
      consistently higher in males than in females. Conclusion: These results suggest
      that clinicians should consider cancer in patients with a platelet count >375 *
      109/l, review reasons for testing and any additional reported symptoms. Until
      these results are replicated on a larger scale, recommendations for clinical
      action cannot be made.

PMID- 29659803
TI  - Corrigendum: Level of agreement between physician and patient assessment of non
      medical health factors.

PMID- 29659805
TI  - The new hypertension guideline: logical but unwise.

PMID- 29659804
TI  - High-content screen for modifiers of Niemann-Pick type C disease in patient
      cells.
AB  - Niemann-Pick type C (NPC) disease is a rare lysosomal storage disease caused
      primarily by mutations in NPC1. NPC1 encodes the lysosomal cholesterol transport
      protein NPC1. The most common NPC1 mutation is a missense mutation (NPC1I1061T)
      that causes misfolding and rapid degradation of mutant protein in the endoplasmic
      reticulum. Cholesterol accumulates in enlarged lysosomes as a result of decreased
      levels of lysosomal NPC1I1061T protein in patient cells. There is currently no
      cure or FDA-approved treatment for patients. We sought to identify novel
      compounds that decrease lysosomal cholesterol storage in NPC1I1061T/I1061T
      patient fibroblasts using a high-content screen with the cholesterol dye, filipin
      and the lysosomal marker, LAMP1. A total of 3532 compounds were screened,
      including 2013 FDA-approved drugs, 327 kinase inhibitors and 760 serum
      metabolites. Twenty-three hits were identified that decreased both filipin and
      LAMP1 signals. The majority of hits (16/21) were histone deacetylase (HDAC)
      inhibitors, a previously described class of modifiers of NPC cholesterol storage.
      Of the remaining hits, the antimicrobial compound, alexidine dihydrochloride had
      the most potent lysosomal cholesterol-reducing activity. Subsequent analyses
      showed that alexidine specifically increased levels of NPC1 transcript and mature
      protein in both control and NPC patient cells. Although unsuitable for systemic
      therapy, alexidine represents a unique tool compound for further NPC studies and
      as a potent inducer of NPC1. Together, these findings confirm the utility of high
      content image-based compound screens of NPC1 patient cells and support extending
      the approach into larger compound collections.

PMID- 29659806
TI  - Evolution of conservative treatment of acute traumatic aortic injuries: lights
      and shadows.
AB  - OBJECTIVES: The objective of this study is to compare early and long-term results
      in terms of survival and aortic complications for traumatic aortic injuries
      depending on the initial management strategy. METHODS: From January 1980 to
      January 2017, 101 patients with aortic injuries were divided into 3 groups
      according to management strategy at admission: 60 patients, conservative
      management; 26 patients, open surgery and 15 patients, endovascular repair. The
      groups were similar in terms of gender and trauma severity scores. RESULTS: All
      but 1 aortic-related complications and aortic-related mortality occurred in the
      conservative group (11.6% conservative vs 2.4% in both surgical and endovascular
      groups, P = 0.091). Total follow-up was 1109.27 patient-years. Survival in the
      conservative, surgical and endovascular group was 71.7%, 80.8% and 79.4% at 1
      year, 68.2%, 80.8% and 79.4% at 5 years and 63.9%, 72.7% and 79.4% at 10 years,
      respectively (log-rank = 0.218). The rate of aortic-related complications was
      58.3% in the conservative cohort. Cox regression identified the following risk
      factors for aortic-related complications: aortic injuries grade >I [odds ratio
      (OR), 3.05; P = 0.021], Trauma Injury Severity Score >50% (OR 1.21; P = 0.042)
      and the decade of treatment (OR 0.49; P = 0.011). CONCLUSIONS: Minimal aortic
      injuries seem to be an amenable target for medical management, but patients
      remain at risk of developing aortic-related complications. Close, long-term
      imaging surveillance is mandatory to detect such complications at an early stage.

PMID- 29659808
TI  - Knowledge and application of European Society of Cardiology (ESC) Guidelines in
      the management of mitral regurgitation: this is not bad but we can do much
      better.

PMID- 29659807
TI  - The Genome Sequence of "Candidatus Fokinia solitaria": Insights on Reductive
      Evolution in Rickettsiales.
AB  - "Candidatus Fokinia solitaria" is an obligate intracellular endosymbiont of a
      unicellular eukaryote, a ciliate of the genus Paramecium. Here, we present the
      genome sequence of this bacterium and subsequent analysis. Phylogenomic analysis
      confirmed the previously reported positioning of the symbiont within the
      "Candidatus Midichloriaceae" family (order Rickettsiales), as well as its high
      sequence divergence from other members of the family, indicative of fast sequence
      evolution. Consistently with this high evolutionary rate, a comparative genomic
      analysis revealed that the genome of this symbiont is the smallest of the
      Rickettsiales to date. The reduced genome does not present flagellar genes, nor
      the pathway for the biosynthesis of lipopolysaccharides (present in all the other
      so far sequenced members of the family "Candidatus Midichloriaceae") or genes for
      the Krebs cycle (present, although not always complete, in Rickettsiales). These
      results indicate an evolutionary trend toward a stronger dependence on the host,
      in comparison with other members of the family. Two alternative scenarios are
      compatible with our results; "Candidatus Fokinia solitaria" could be either a
      recently evolved, vertically transmitted mutualist, or a parasite with a high
      host-specificity.

PMID- 29659809
TI  - A new mouse model of ARX dup24 recapitulates the patients' behavioral and fine
      motor alterations.
AB  - The aristaless-related homeobox (ARX) transcription factor is involved in the
      development of GABAergic and cholinergic neurons in the forebrain. ARX mutations
      have been associated with a wide spectrum of neurodevelopmental disorders in
      humans, among which the most frequent, a 24 bp duplication in the polyalanine
      tract 2 (c.428_451dup24), gives rise to intellectual disability, fine motor
      defects with or without epilepsy. To understand the functional consequences of
      this mutation, we generated a partially humanized mouse model carrying the
      c.428_451dup24 duplication (Arxdup24/0) that we characterized at the behavior,
      neurological and molecular level. Arxdup24/0 males presented with hyperactivity,
      enhanced stereotypies and altered contextual fear memory. In addition, Arxdup24/0
      males had fine motor defects with alteration of reaching and grasping abilities.
      Transcriptome analysis of Arxdup24/0 forebrains at E15.5 showed a down-regulation
      of genes specific to interneurons and an up-regulation of genes normally not
      expressed in this cell type, suggesting abnormal interneuron development.
      Accordingly, interneuron migration was altered in the cortex and striatum between
      E15.5 and P0 with consequences in adults, illustrated by the defect in the
      inhibitory/excitatory balance in Arxdup24/0 basolateral amygdala. Altogether, we
      showed that the c.428_451dup24 mutation disrupts Arx function with a direct
      consequence on interneuron development, leading to hyperactivity and defects in
      precise motor movement control and associative memory. Interestingly, we
      highlighted striking similarities between the mouse phenotype and a cohort of 33
      male patients with ARX c.428_451dup24, suggesting that this new mutant mouse line
      is a good model for understanding the pathophysiology and evaluation of
      treatment.

PMID- 29659810
TI  - Conservation of Sex-Linked Markers among Conspecific Populations of a Viviparous
      Skink, Niveoscincus ocellatus, Exhibiting Genetic and Temperature-Dependent Sex
      Determination.
AB  - Sex determination systems are exceptionally diverse and have undergone multiple
      and independent evolutionary transitions among species, particularly reptiles.
      However, the mechanisms underlying these transitions have not been established.
      Here, we tested for differences in sex-linked markers in the only known reptile
      that is polymorphic for sex determination system, the spotted snow skink,
      Niveoscincus ocellatus, to quantify the genomic differences that have accompanied
      this transition. In a highland population, sex is determined genetically, whereas
      in a lowland population, offspring sex ratio is influenced by temperature. We
      found a similar number of sex-linked loci in each population, including shared
      loci, with genotypes consistent with male heterogamety (XY). However, population
      specific linkage disequilibrium suggests greater differentiation of sex
      chromosomes in the highland population. Our results suggest that transitions
      between sex determination systems can be facilitated by subtle genetic
      differences.

PMID- 29659811
TI  - Complete Genome Sequence of Streptococcus ruminantium sp. nov. GUT-187T (=DSM
      104980T =JCM 31869T), the Type Strain of S. ruminantium, and Comparison with
      Genome Sequences of Streptococcus suis Strains.
AB  - Streptococcus ruminantium sp. nov. of type strain GUT-187T, previously classified
      as Streptococcus suis serotype 33, is a recently described novel streptococcal
      species. This study was designed to determine the complete genome sequence of S.
      ruminantium GUT-187T using a combination of Oxford Nanopore and the Illumina
      platform, and to compare this sequence with the genomes of 27 S. suis
      representative strains. The genome of GUT-187T was 2,090,539 bp in size, with a
      GC content of 40.01%. This genome contained 1,961 predicted protein coding DNA
      sequences (CDSs); of these, 1,685 (85.9%) showed similarity with S. suis CDSs. Of
      the remaining 276 CDSs, 81 (29.3%) showed some degree of similarity with CDSs of
      other streptococcal species. The genome of GUT-187T contained no intact prophage.
      The numbers of prophages and CRISPR spacers, as well as the presence or absence
      of genes encoding CRISPR-associated proteins, differed in S. ruminantium and S.
      suis. A phylogenetic analysis indicates that GUT-187T may be outgroup to the S.
      suis strains in our sample, thereby justifying its classification as distinct
      species. Gene mapping indicated 10.2 times of massive genome rearrangements in
      average occurred between S. ruminantium and S. suis. There was no significant
      statistical difference in clusters of orthologous group distribution between S.
      ruminantium and S. suis.

PMID- 29659812
TI  - The genome sequence and transcriptome of Potentilla micrantha and their
      comparison to Fragaria vesca (the woodland strawberry).
AB  - Background: The genus Potentilla is closely related to that of Fragaria, the
      economically important strawberry genus. Potentilla micrantha is a species that
      does not develop berries but shares numerous morphological and ecological
      characteristics with Fragaria vesca. These similarities make P. micrantha an
      attractive choice for comparative genomics studies with F. vesca. Findings: In
      this study, the P. micrantha genome was sequenced and annotated, and RNA-Seq data
      from the different developmental stages of flowering and fruiting were used to
      develop a set of gene predictions. A 327 Mbp sequence and annotation of the
      genome of P. micrantha, spanning 2674 sequence contigs, with an N50 size of
      335,712, estimated to cover 80% of the total genome size of the species was
      developed. The genus Potentilla has a characteristically larger genome size than
      Fragaria, but the recovered sequence scaffolds were remarkably collinear at the
      micro-syntenic level with the genome of F. vesca, its closest sequenced relative.
      A total of 33,602 genes were predicted, and 95.1% of bench-marking universal
      single-copy orthologous genes were complete within the presented sequence. Thus,
      we argue that the majority of the gene-rich regions of the genome have been
      sequenced. Conclusions: Comparisons of RNA-Seq data from the stages of floral and
      fruit development revealed genes differentially expressed between P. micrantha
      and F. vesca.The data presented are a valuable resource for future studies of
      berry development in Fragaria and the Rosaceae and they also shed light on the
      evolution of genome size and organization in this family.

PMID- 29659814
TI  - The first whole transcriptomic exploration of pre-oviposited early chicken
      embryos using single and bulked embryonic RNA-sequencing.
AB  - Background: The chicken is a valuable model organism, especially in evolutionary
      and embryology research because its embryonic development occurs in the egg.
      However, despite its scientific importance, no transcriptome data have been
      generated for deciphering the early developmental stages of the chicken because
      of practical and technical constraints in accessing pre-oviposited embryos.
      Findings: Here, we determine the entire transcriptome of pre-oviposited avian
      embryos, including oocyte, zygote, and intrauterine embryos from Eyal-giladi and
      Kochav stage I (EGK.I) to EGK.X collected using a noninvasive approach for the
      first time. We also compare RNA-sequencing data obtained using a bulked embryo
      sequencing and single embryo/cell sequencing technique. The raw sequencing data
      were preprocessed with two genome builds, Galgal4 and Galgal5, and the expression
      of 17,108 and 26,102 genes was quantified in the respective builds. There were
      some differences between the two techniques, as well as between the two genome
      builds, and these were affected by the emergence of long intergenic noncoding RNA
      annotations. Conclusion: The first transcriptome datasets of pre-oviposited early
      chicken embryos based on bulked and single embryo sequencing techniques will
      serve as a valuable resource for investigating early avian embryogenesis, for
      comparative studies among vertebrates, and for novel gene annotation in the
      chicken genome.

PMID- 29659813
TI  - Draft genome of the protandrous Chinese black porgy, Acanthopagrus schlegelii.
AB  - Background: As one of the most popular and valuable commercial marine fishes in
      China and East Asian countries, the Chinese black porgy (Acanthopagrus
      schlegelii), also known as the blackhead seabream, has some attractive
      characteristics such as fast growth rate, good meat quality, resistance to
      diseases, and excellent adaptability to various environments. Furthermore, the
      black porgy is a good model for investigating sex changes in fish due to its
      protandrous hermaphroditism. Here, we obtained a high-quality genome assembly of
      this interesting teleost species and performed a genomic survey on potential
      genes associated with the sex-change phenomenon. Findings: We generated 175.4
      gigabases (Gb) of clean sequence reads using a whole-genome shotgun sequencing
      strategy. The final genome assembly is approximately 688.1 megabases (Mb),
      accounting for 93% of the estimated genome size (739.6 Mb). The achieved scaffold
      N50 is 7.6 Mb, reaching a relatively high level among sequenced fish species. We
      identified 19 465 protein-coding genes, which had an average transcript length of
      17.3 kb. By performing a comparative genomic analysis, we found 3 types of genes
      potentially associated with sex change, which are useful for studying the genetic
      basis of the protandrous hermaphroditism. Conclusions: We provide a draft genome
      assembly of the Chinese black porgy and discuss the potential genetic mechanisms
      of sex change. These data are also an important resource for studying the biology
      and for facilitating breeding of this economically important fish.

PMID- 29659816
TI  - The relative price of healthy and less healthy foods available in Australian
      school canteens.
AB  - School canteens have an important role in modelling a healthy food environment.
      Price is a strong predictor of food and beverage choice. This study compared the
      relative price of healthy and less healthy lunch and snack items sold within
      Australian school canteens. A convenience sample of online canteen menus from
      five Australian states were selected (100 primary and 100 secondary schools).
      State-specific canteen guidelines were used to classify menu items into 'green'
      (eat most), 'amber' (select carefully) and 'red' (not recommended in schools).
      The price of the cheapest 'healthy' lunch (vegetable-based 'green') and snack
      ('green' fruit) item was compared to the cheapest 'less healthy' ('amber/red')
      lunch and snack item, respectively, using an un-paired t-test. The relative price
      of the 'healthy' items and the 'less healthy' items was calculated to determine
      the proportion of schools that sold the 'less healthy' item cheaper. The mean
      cost of the 'healthy' lunch items was greater than the 'less healthy' lunch items
      for both primary (AUD $0.70 greater) and secondary schools ($0.50 greater; p <
      0.01). For 75% of primary and 57% of secondary schools, the selected 'less
      healthy' lunch item was cheaper than the 'healthy' lunch item. For 41% of primary
      and 48% of secondary schools, the selected 'less healthy' snack was cheaper than
      the 'healthy' snack. These proportions were greatest for primary schools located
      in more, compared to less, disadvantaged areas. The relative price of foods sold
      within Australian school canteens appears to favour less healthy foods. School
      canteen healthy food policies should consider the price of foods sold.

PMID- 29659817
TI  - Effect of resource availability on evolution of virulence and competition in an
      environmentally transmitted pathogen.
AB  - Understanding ecological and epidemiological factors driving pathogen evolution
      in contemporary time scales is a major challenge in modern health management.
      Pathogens that replicate outside the hosts are subject to selection imposed by
      ambient environmental conditions. Increased nutrient levels could increase
      pathogen virulence by pre-adapting for efficient use of resources upon contact to
      a nutrient rich host or by favouring transmission of fast-growing virulent
      strains. We measured changes in virulence and competition in Flavobacterium
      columnare, a bacterial pathogen of freshwater fish, under high and low nutrient
      levels. To test competition between strains in genotype mixtures, we developed a
      quantitative real-time PCR assay. We found that a virulent strain maintained its
      virulence and outcompeted less virulent strains independent of the nutrient level
      and resource renewal rate while a less virulent strain further lost virulence in
      chemostats under low nutrient level and over long-term serial culture under high
      nutrient level. Our results suggest that increased outside-host nutrient levels
      might maintain virulence in less virulent strains and increase their contribution
      to epidemics in aquaculture. The results highlight a need to further explore the
      role of resource in the outside-host environment in maintaining strain diversity
      and driving evolution of virulence among environmentally growing pathogens.

PMID- 29659815
TI  - Plant Lineage-Specific Amplification of Transcription Factor Binding Motifs by
      Miniature Inverted-Repeat Transposable Elements (MITEs).
AB  - Transposable elements are one of the main drivers of plant genome evolution.
      Transposon insertions can modify the gene coding capacity or the regulation of
      their expression, the latter being a more subtle effect, and therefore
      particularly useful for evolution. Transposons have been show to contain
      transcription factor binding sites that can be mobilized upon transposition with
      the potential to integrate new genes into transcriptional networks. Miniature
      inverted-repeat transposable elements (MITEs) are a type of noncoding DNA
      transposons that could be particularly suited as a vector to mobilize
      transcription factor binding sites and modify transcriptional networks during
      evolution. MITEs are small in comparison to other transposons and can be excised,
      which should make them less mutagenic when inserting into promoters. On the other
      hand, in spite of their cut-and-paste mechanisms of transposition, they can reach
      very high copy numbers in genomes. We have previously shown that MITEs have
      amplified and redistributed the binding motif of the E2F transcription factor in
      different Brassicas. Here, we show that MITEs have amplified and mobilized the
      binding motifs of the bZIP60 and PIF3 transcription factors in peach and Prunus
      mume, and the TCP15/23 binding motif in tomato. Our results suggest that MITEs
      could have rewired new genes into transcriptional regulatory networks that are
      responsible for important adaptive responses and breeding traits in plants, such
      as stress responses, flowering time, or fruit ripening. The results presented
      here therefore suggest a general impact of MITEs in the evolution of
      transcriptional regulatory networks in plants.

PMID- 29659818
TI  - Surgical treatment of huge left ventricular outflow tract pseudoaneurysm.
AB  - Pseudoaneurysms arising from the left ventricular outflow tract are rarely
      reported. We report a 26-year-old man who was admitted with paroxysmal chest pain
      and dyspnoea on exertion. Computed tomography revealed the presence of a
      pseudoaneurysm (93 * 77 mm), and the communication was below the aortic annulus.
      Through median sternotomy, a huge pulsatile pseudoaneurysm was exposed, and an 8
      mm-diameter communication of the pseudoaneurysm in the left ventricular outflow
      tract wall was visualized. The defect was successfully repaired, and the
      postoperative course was uneventful.

PMID- 29659819
TI  - Mindfulness-based lifestyle programs for the self-management of Parkinson's
      disease in Australia.
AB  - Despite emerging evidence suggesting positive outcomes of mindfulness training
      for the self-management of other neurodegenerative diseases, limited research has
      explored its effect on the self-management of Parkinson's disease (PD). We aimed
      to characterize the experiences of individuals participating in a facilitated,
      group mindfulness-based lifestyle program for community living adults with Stage
      2 PD and explore how the program influenced beliefs about self-management of
      their disease. Our longitudinal qualitative study was embedded within a
      randomized controlled trial exploring the impact of a 6-week mindfulness-based
      lifestyle program on patient-reported function. The study was set in Melbourne,
      Australia in 2012-2013. We conducted semi-structured interviews with participants
      before, immediately after, and 6 months following participation in the program.
      Sixteen participants were interviewed prior to commencing the program. Of these,
      12 were interviewed shortly after its conclusion, and 9 interviewed at 6 months.
      Prior to the program, participants felt a lack of control over their illness. A
      desire for control and a need for alternative tools for managing the progression
      of PD motivated many to engage with the program. Following the program, where
      participants experienced an increase in mindfulness, many became more accepting
      of disease progression and reported improved social relationships and self
      confidence in managing their disease. Mindfulness-based lifestyle programs have
      the potential for increasing both participants' sense of control over their
      reactions to disease symptoms as well as social connectedness. Community-based
      mindfulness training may provide participants with tools for self-managing a
      number of the consequences of Stage 2 PD.

PMID- 29659820
TI  - Recent mouse models and vaccine candidates for preventing chronic/latent
      tuberculosis infection and its reactivation.
AB  - Tuberculosis (TB) remains a major challenge in public health worldwide. Until
      today, the only widely used and approved vaccine is the Mycobacterium bovis
      bacille Calmette-Guerin (BCG). This vaccine provides a highly variable level of
      protection against the active, pulmonary form of tuberculosis, and practically
      none against the latent form of TB infection. This disparity in protection has
      been extensively studied, and for this reason, several groups have focused their
      research on the quest for attenuated vaccines based on M. tuberculosis or on the
      identification of latency-associated antigens that can be incorporated into
      modified BCG, or that can be used as adjuvanted subunit vaccines. In order to
      seek new potential antigens relevant for infection, some researchers have
      performed experiments with highly sensitive techniques such as transcriptomic and
      proteomic analyses using sputum samples from humans or by using mouse models
      resembling several aspects of TB. In this review, we focus on reports of new
      mouse models or mycobacterial antigens recently tested for developing vaccine
      candidates against chronic/latent tuberculosis and its reactivation.

PMID- 29659821
TI  - Finnish NGOs promoting health equity in the context of welfare economy.
AB  - Health inequality is a national challenge in Finland. The WHO global strategy of
      Health for All implies that all people should have an equal opportunity to
      develop and maintain their health through fair and just access to health
      resources. This article examines the role of Finnish Non-Governmental
      Organizations (NGO) in strengthening the health equity. The article presents the
      strategy and specific criteria constructed by the NGOs to promote health equity
      in society. The health equity criteria and welfare economy strategy are combined
      to a framework which NGOs can utilize in their work to promote health equity. The
      welfare economy strategy describes the important issues that NGOs have to address
      when working towards a specific societal goal, in this case equity. The health
      equity criteria in turn are an instrument for the practical implementation of the
      preconditions of equity.

PMID- 29659822
TI  - Development and application of CRISPR/Cas9 technologies in genomic editing.
AB  - Genomic editing to correct disease-causing mutations is a promising approach for
      the treatment of human diseases. As a simple and programmable nuclease-based
      genomic editing tool, the clustered regularly interspaced short palindromic
      repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system has substantially
      improved the ability to make precise changes in the human genome. Rapid
      development of CRISPR-based technologies in recent years has expanded its
      application scope and promoted CRISPR-based therapies in preclinical trails.
      Here, we review the application of the CRISPR system over the last 2 years;
      including its development and application in base editing, transcription
      modulation and epigenetic editing, genomic-scale screening, and cell and embryo
      therapy. Finally, the prospects and challenges related to application of
      CRISPR/Cas9 technologies are discussed.

PMID- 29659823
TI  - A hyperactivating proinflammatory RIPK2 allele associated with early-onset
      osteoarthritis.
AB  - Osteoarthritis (OA) is a common debilitating disease characterized by abnormal
      remodeling of the cartilage and bone of the articular joint. Ameliorating
      therapeutics are lacking due to limited understanding of the molecular pathways
      affecting disease initiation and progression. Notably, although a link between
      inflammation and overt OA is well established, the role of inflammation as a
      driver of disease occurrence is highly disputed. We analyzed a family with
      dominant inheritance of early-onset OA and found that affected individuals
      harbored a rare variant allele encoding a significant amino acid change
      (p.Asn104Asp) in the kinase domain of receptor interacting protein kinase 2
      (RIPK2), which transduces signals from activated bacterial peptidoglycan sensors
      through the NF-kappaB pathway to generate a proinflammatory immune response.
      Functional analyses of RIPK2 activity in zebrafish embryos indicated that the
      variant RIPK2104Asp protein is hyperactive in its signaling capacity, with
      augmented ability to activate the innate immune response and the NF-kappaB
      pathway and to promote upregulation of OA-associated genes. Further we show a
      second allele of RIPK2 linked to an inflammatory disease associated with
      arthritis also has enhanced activity stimulating the NF-kappaB pathway. Our
      studies reveal for the first time the inflammatory response can function as a
      gatekeeper risk factor for OA.

PMID- 29659824
TI  - Education Corner.

PMID- 29659825
TI  - Differential effects of 14-3-3 dimers on Tau phosphorylation, stability and
      toxicity in vivo.
AB  - Neurodegenerative dementias collectively known as Tauopathies involve aberrant
      phosphorylation and aggregation of the neuronal protein Tau. The largely neuronal
      14-3-3 proteins are also elevated in the central nervous system (CNS) and
      cerebrospinal fluid of Tauopathy patients, suggesting functional linkage. We use
      the simplicity and genetic facility of the Drosophila system to investigate in
      vivo whether 14-3-3s are causal or synergistic with Tau accumulation in
      precipitating pathogenesis. Proteomic, biochemical and genetic evidence
      demonstrate that both Drosophila 14-3-3 proteins interact with human wild-type
      and mutant Tau on multiple sites irrespective of their phosphorylation state. 14
      3-3 dimers regulate steady-state phosphorylation of both wild-type and the R406W
      mutant Tau, but they are not essential for toxicity of either variant. Moreover,
      14-3-3 elevation itself is not pathogenic, but recruitment of dimers on
      accumulating wild-type Tau increases its steady-state levels ostensibly by
      occluding access to proteases in a phosphorylation-dependent manner. In contrast,
      the R406W mutant, which lacks a putative 14-3-3 binding site, responds
      differentially to elevation of each 14-3-3 isoform. Although excess 14-3-3zeta
      stabilizes the mutant protein, elevated D14-3-3E has a destabilizing effect
      probably because of altered 14-3-3 dimer composition. Our collective data
      demonstrate the complexity of 14-3-3/Tau interactions in vivo and suggest that 14
      3-3 attenuation is not appropriate ameliorative treatment of Tauopathies.
      Finally, we suggest that 'bystander' 14-3-3s are recruited by accumulating Tau
      with the consequences depending on the composition of available dimers within
      particular neurons and the Tau variant.

PMID- 29659826
TI  - Association between ambient air pollution and pregnancy rate in women who
      underwent IVF.
AB  - STUDY QUESTION: Are the concentrations of five criteria air pollutants associated
      with probabilities of biochemical pregnancy loss and intrauterine pregnancy in
      women? SUMMARY ANSWER: Increased concentrations of ambient particulate matter
      (PM10), nitrogen dioxide (NO2), carbon monoxide (CO) during controlled ovarian
      stimulation (COS) and after embryo transfer were associated with a decreased
      probability of intrauterine pregnancy. WHAT IS KNOWN ALREADY: Exposure to high
      ambient air pollution was suggested to be associated with low fertility and high
      early pregnancy loss in women. STUDY DESIGN, SIZE, DURATION: Using a
      retrospective cohort study design, we analysed 6621 cycles of 4581 patients who
      underwent one or more fresh IVF cycles at a fertility centre from January 2006 to
      December 2014, and lived in Seoul at the time of IVF treatment.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: To estimate patients' individual
      exposure to air pollution, we computed averages of hourly concentrations of five
      air pollutants including PM10, NO2, CO, sulphur dioxide (SO2) and ozone (O3)
      measured at 40 regulatory monitoring sites in Seoul for each of the four exposure
      periods: period 1 (start of COS to oocyte retrieval), period 2 (oocyte retrieval
      to embryo transfer), period 3 (embryo transfer to hCG test), and period 4 (start
      of COS to hCG test). Hazard ratios (HRs) from the time-varying Cox-proportional
      hazards model were used to estimate probabilities of biochemical pregnancy loss
      and intrauterine pregnancy for an interquartile range (IQR) increase in each air
      pollutant concentration during each period, after adjusting for individual
      characteristics. We tested the robustness of the result using generalised linear
      mixed model, accounting for within-woman correlation. MAIN RESULTS AND THE ROLE
      OF CHANCE: Mean age of the women was 35 years. Average BMI was 20.9 kg/m2 and the
      study population underwent 1.4 IVF cycles on average. Cumulative pregnancy rate
      in multiple IVF cycles was 51.3% per person. Survival analysis showed that air
      pollution during periods 1 and 3 was generally associated with IVF outcomes.
      Increased NO2 (adjusted HR = 0.93, 95% CI: 0.87, 0.99) and CO (0.94, 95% CI:
      0.89, 1.00) during period 1 were associated with decreased probability of
      intrauterine pregnancy. PM10 (0.92, 95% CI: 0.85, 0.99), NO2 (0.93, 95% CI =
      0.86, 1.00) and CO (0.93, 95% CI: 0.87, 1.00) levels during period 3 were also
      inversely associated with intrauterine pregnancy. Both PM10 (1.17, 95% CI: 1.04
      1.33) and NO2 (1.18, 95% CI: 1.03, 1.34) during period 3 showed positive
      associations with biochemical pregnancy loss. LIMITATIONS, REASONS FOR CAUTION:
      The district-specific ambient air pollution treated as an individual exposure may
      not represent the actual level of each woman's exposure to air pollution.
      Smoking, working status, parity or gravidity of women, and semen analysis data
      were not included in the analysis. WIDER IMPLICATIONS OF THE FINDINGS: This study
      provided evidence of an association between increased ambient concentrations of
      PM10, NO2 and CO and reduced probabilities for achieving intrauterine pregnancy
      using multiple IVF cycle data. Specifically, our results indicated that lower
      intrauterine pregnancy rates in IVF cycles may be linked to ambient air pollution
      during COS and the post-transfer period. STUDY FUNDING/COMPETING INTEREST(S):
      This research was supported by Basic Science Research Program through the
      National Research Foundation of Korea (NRF) funded by the Ministry of Education
      (2013 R1A6A3A04059017, 2016 R1D1A1B03933410 and 2018 R1A2B6004608) and the
      National Cancer Center of Korea (NCC-1810220-01). The authors report no conflicts
      of interest. TRIAL REGISTRATION NUMBER: N/A.

PMID- 29659827
TI  - A MEI1 homozygous missense mutation associated with meiotic arrest in a
      consanguineous family.
AB  - Although meiotic arrest in males is observed in about 25% of azoospermic
      patients, pure homogeneous arrest in all seminiferous tubules is less frequent,
      and may be due to mutation of a single gene. However, given the large number of
      genes involved in meiosis, this gives rises to extensive genetic heterogeneity.
      Only two genetic abnormalities have been reported on a regular basis: the X
      linked exonic TEX11 deletion, and the AZFb microdeletion on the Y chromosome.
      Other single gene defects were private and found in consanguineous families.
      Here, we report on a homozygous missense mutation in the gene coding for meiotic
      double-stranded break formation protein 1 (MEI1; c.C3307T:p.R1103W) observed in
      two brothers (from a consanguineous Tunisian family) with non-obstructive
      azoospermia and meiotic arrest. A fertile brother was heterozygous for the
      mutation. All the queried databases predicted that this mutation is damaging, and
      it has previously been reported that Mei1 knock-out is associated with meiotic
      arrest in a murine model. Hence, meiotic arrest in the two brothers was probably
      caused by an alteration in a gene known to be fundamental for chromosome
      synapsis.

PMID- 29659828
TI  - The next generation of precision medicine: observational studies, electronic
      health records, biobanks and continuous monitoring.
AB  - Precision medicine can utilize new techniques in order to more effectively
      translate research findings into clinical practice. In this article, we first
      explore the limitations of traditional study designs, which stem from (to name a
      few): massive cost for the assembly of large patient cohorts; non-representative
      patient data; and the astounding complexity of human biology. Second, we propose
      that harnessing electronic health records and mobile device biometrics coupled to
      longitudinal data may prove to be a solution to many of these problems by
      capturing a 'real world' phenotype. We envision that future biomedical research
      utilizing more precise approaches to patient care will utilize continuous and
      longitudinal data sources.

PMID- 29659829
TI  - Take a break!

PMID- 29659831
TI  - Institutional delivery in India, 2004-14: unravelling the equity-enhancing
      contributions of the public sector.
AB  - To achieve faster and equitable improvements in maternal and child health
      outcomes, the government of India launched the National Rural Health Mission in
      2005. This paper describes the equity-enhancing role of the public sector in
      increasing use of institutional delivery care services in India between 2004 and
      2014. Information on 24 661 births from nationally representative survey data for
      2004 and 2014 is analysed. Concentration index is computed to describe
      socioeconomic-rank-related relative inequalities in institutional delivery and
      decomposition is used to assess the contributions of public and private sectors
      in overall socioeconomic inequality. Multilevel logistic regression is applied to
      examine the changes in socioeconomic gradient between 2004 and 2014. The analysis
      finds that utilization of institutional delivery care in India increased from 43%
      in 2004 to 83% in 2014. The bulk of the increase was in public sector use (21% in
      2004 to 53% in 2014) with a modest increase in private sector use (22% in 2004 to
      30% in 2014). The shift from a pro-rich to pro-poor distribution of public sector
      use is confirmed. Decomposition analysis indicates that 51% of these reductions
      in socioeconomic inequality are associated with improved pro-poor distribution of
      public sector births. Multilevel logistic regressions confirm the disappearance
      of a wealth-based gradient in public sector births between 2004 and 2014. We
      conclude that public health investments in India have significantly contributed
      towards an equitable increase in the coverage of institutional delivery care.
      Sustained policy efforts are necessary, however, with an emphasis on education,
      sociocultural and geographical factors to ensure universal coverage of
      institutional delivery care services in India.

PMID- 29659832
TI  - Average sperm count remains unchanged despite reduction in maternal smoking:
      results from a large cross-sectional study with annual investigations over 21
      years.
AB  - STUDY QUESTION: How are temporal trends in lifestyle factors, including exposure
      to maternal smoking in utero, associated to semen quality in young men from the
      general population? SUMMARY ANSWER: Exposure to maternal smoking was associated
      with lower sperm counts but no overall increase in sperm counts was observed
      during the study period despite a decrease in this exposure. WHAT IS KNOWN
      ALREADY: Meta-analyses suggest a continuous decline in semen quality but few
      studies have investigated temporal trends in unselected populations recruited and
      analysed with the same protocol over a long period and none have studied
      simultaneous trends in lifestyle factors. STUDY DESIGN, SIZE, DURATION: Cross
      sectional population-based study including ~300 participants per year (total
      number = 6386) between 1996 and 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS:
      The study is based on men from the Greater Copenhagen area, Denmark, with a
      median age of 19 years, and unselected with regard to fertility status and semen
      quality. The men delivered a semen sample, had a blood sample drawn and a
      physical examination performed and answered a comprehensive questionnaire,
      including information on lifestyle and the mother's pregnancy. Temporal trends in
      semen quality and lifestyle were illustrated graphically, and trends in semen
      parameters and the impact of prenatal and current lifestyle factors were explored
      in multiple regression analyses. MAIN RESULTS AND THE ROLE OF CHANCE: Throughout
      the study period, 35% of the men had low semen quality. Overall, there were no
      persistent temporal trends in semen quality, testicular volume or levels of
      follicle-stimulating hormone over the 21 years studied. The men's alcohol intake
      was lowest between 2011 and 2016, whereas BMI, use of medication and smoking
      showed no clear temporal trends. Parental age increased, and exposure in utero to
      maternal smoking declined from 40% among men investigated in 1996-2000 to 18%
      among men investigated in 2011-2016. Exposure to maternal smoking was associated
      with lower sperm counts but no overall increase in sperm counts was observed
      despite the decrease in this exposure. LIMITATIONS, REASONS FOR CAUTION:
      Information of current and prenatal lifestyle was obtained by self-report, and
      the men delivered only one semen sample each. WIDER IMPLICATIONS OF THE FINDINGS:
      The significant decline in in utero exposure to maternal smoking, which was not
      reflected in an overall improvement of semen quality at the population level,
      suggest that other unknown adverse factors may maintain the low semen quality
      among Danish men. STUDY FUNDING/COMPETING INTEREST(S): The study has received
      financial support from the ReproUnion; the Research fund of Rigshospitalet,
      Copenhagen University Hospital; the European Union (Contract numbers BMH4-CT96
      0314,QLK4-CT-1999-01422, QLK4-CT-2002-00603, FP7/2007-2013, DEER Grant agreement
      no. 212844); the Danish Ministry of Health; the Danish Environmental Protection
      Agency; A.P. Moller and wife Chastine McKinney Mollers foundation; and Svend
      Andersens Foundation. None of the funders had any role in the study design,
      collection, analysis or interpretation of data, writing of the paper or
      publication decisions. TRIAL REGISTRATION NUMBER: N/A.

PMID- 29659830
TI  - Genome-wide association study identifies nine novel loci for 2D:4D finger ratio,
      a putative retrospective biomarker of testosterone exposure in utero.
AB  - The ratio of the length of the index finger to that of the ring finger (2D:4D) is
      sexually dimorphic and is commonly used as a non-invasive biomarker of prenatal
      androgen exposure. Most association studies of 2D:4D ratio with a diverse range
      of sex-specific traits have typically involved small sample sizes and have been
      difficult to replicate, raising questions around the utility and precise meaning
      of the measure. In the largest genome-wide association meta-analysis of 2D:4D
      ratio to date (N = 15 661, with replication N = 75 821), we identified 11 loci (9
      novel) explaining 3.8% of the variance in mean 2D:4D ratio. We also found weak
      evidence for association (beta = 0.06; P = 0.02) between 2D:4D ratio and
      sensitivity to testosterone [length of the CAG microsatellite repeat in the
      androgen receptor (AR) gene] in females only. Furthermore, genetic variants
      associated with (adult) testosterone levels and/or sex hormone-binding globulin
      were not associated with 2D:4D ratio in our sample. Although we were unable to
      find strong evidence from our genetic study to support the hypothesis that 2D:4D
      ratio is a direct biomarker of prenatal exposure to androgens in healthy
      individuals, our findings do not explicitly exclude this possibility, and
      pathways involving testosterone may become apparent as the size of the discovery
      sample increases further. Our findings provide new insight into the underlying
      biology shaping 2D:4D variation in the general population.

PMID- 29659834
TI  - An open-source, integrated pedigree data management and visualization tool for
      genetic epidemiology.
AB  - With advances in genetic epidemiology, increasingly large amounts of pedigree
      related information are being collected by family studies, including twin
      studies. To date, biomedical data management systems that cater for family data
      have usually done so as part of their standard (non-family-centric) data model.
      Consequently, data managers with computing expertise are needed to extract family
      datasets and perform family-centric operations. We present a robust approach to
      handling large family datasets. Our approach is implemented as a new module which
      extends the capabilities of The Ark, an open-source web-based biomedical data
      management tool. Using an algorithm designed by the authors, the pedigree module
      dynamically infers family relationships for any selected subject (not necessarily
      the proband). A web interface allows researchers to create, update, delete and
      navigate parental and twin relationships between subjects, and bulk import/export
      pedigrees. Consanguineous relationships can be captured, and configurable
      pedigree visualizations generated. A web services interface provides
      interoperability.

PMID- 29659833
TI  - Ift172 conditional knock-out mice exhibit rapid retinal degeneration and protein
      trafficking defects.
AB  - Intraflagellar transport (IFT) is a bidirectional transport process that occurs
      along primary cilia and specialized sensory cilia, such as photoreceptor
      outersegments. Genes coding for various IFT components are associated with
      ciliopathies. Mutations in IFT172 lead to diseases ranging from isolated retinal
      degeneration to severe syndromic ciliopathies. In this study, we created a mouse
      model of IFT172-associated retinal degeneration to investigate the ocular disease
      mechanism. We found that depletion of IFT172 in rod photoreceptors leads to a
      rapid degeneration of the retina, with severely reduced electroretinography (ERG)
      responses by 1 month and complete outer-nuclear layer (ONL) degeneration by 2
      months. We investigated molecular mechanisms of degeneration and show that IFT172
      protein reduction leads to mislocalization of specific photoreceptor outersegment
      (OS) proteins (RHO, RP1, IFT139), aberrant light-driven translocation of alpha
      transducin and altered localization of glioma-associated oncogene family member 1
      (GLI1). This mouse model exhibits key features of the retinal phenotype observed
      in patients with IFT172-associated blindness and can be used for in vivo testing
      of ciliopathy therapies.

PMID- 29659835
TI  - Anti-Mullerian hormone levels and incidence of early natural menopause in a
      prospective study.
AB  - STUDY QUESTION: Are anti-Mullerian hormone (AMH) levels assessed in women aged 32
      44 associated with risk of incident early natural menopause? SUMMARY ANSWER: We
      observed strong, significant associations between lower AMH levels and higher
      risk of early menopause. WHAT IS KNOWN ALREADY: The ability to predict risk early
      menopause, defined as menopause before age 45, prior to fertility decline would
      improve options for family planning and cardiovascular disease prevention. Though
      AMH is an established marker of menopause timing in older reproductive-aged
      women, whether AMH is associated with risk of early menopause has not been
      evaluated. STUDY DESIGN, SIZE, DURATION: We assessed these relations in a nested
      case-control study within the prospective Nurses' Health Study II cohort.
      Premenopausal blood samples were collected in 1996-1999. Participants were
      followed until 2011 for early natural menopause, with follow-up rates >94%.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: Early menopause cases (n = 327) were
      women reporting natural menopause between blood collection and age 45. Controls
      (n = 491) experienced menopause after age 45 and included 327 cases matched to
      controls on the basis of age at blood draw (+/-4 months) and other factors. AMH
      levels up to 12 years before early menopause were assayed in 2016. MAIN RESULTS
      AND THE ROLE OF CHANCE: In multivariable conditional logistic regression models
      adjusting for matching factors, body mass index, smoking, parity, oral
      contraceptive use, and other factors, each 0.10 ng/ml decrease in AMH was
      associated with a 14% higher risk of early menopause (95% confidence interval
      (CI) 1.10 to 1.18; P < 0.001). In polynomial regression models including linear
      and quadratic terms for AMH, odds ratios for early menopause for women with AMH
      levels of 1.5, 1.0 and 0.5 ng/ml compared to 2.0 ng/ml were 2.6, 7.5 and 23 (all
      P < 0.001). Significant associations were observed irrespective of smoking
      status, adiposity, infertility history and menstrual cycle characteristics.
      Furthermore, models assessing the predictive ability of AMH showed high
      concordance, and C-statistics were high, ranging from 0.68 (age <=35) to 0.93
      (age 42). LIMITATIONS, REASONS FOR CAUTION: Our population was relatively
      homogenous with respect to race/ethnicity. Further work in more ethnically
      diverse populations is needed. WIDE IMPLICATION OF THE FINDINGS: To our
      knowledge, this is the first prospective study to evaluate whether AMH levels are
      associated with early menopause. These findings support the utility of AMH as a
      clinical marker of early menopause in otherwise healthy women. STUDY
      FUNDING/COMPETING INTEREST(S): This project was supported by UM1CA176726,
      R01CA67262, and R01HD078517 from the U.S. Department of Health and Human
      Services, National Institutes of Health. No competing interests declared.

PMID- 29659836
TI  - Efficacy and safety of ceftazidime/avibactam: a systematic review and meta
      analysis.
AB  - Background: Ceftazidime/avibactam is approved for complicated intra-abdominal and
      urinary tract infections (UTIs) based on results from randomized controlled
      trials (RCTs). Data regarding its effectiveness in treating hospital-acquired
      infections or resistant pathogens have not been systematically compiled. Methods:
      A systematic review and meta-analysis including RCTs evaluating
      ceftazidime/avibactam versus comparator for the treatment of any infection.
      Primary outcome was 30 day all-cause mortality. Subgroups of hospital-acquired
      infections and specific resistance phenotypes were planned. Results: Seven
      publications (eight trials, 4093 patients) were included, reporting a baseline
      ~25% of ESBL-carrying Enterobacteriaceae. No significant difference between
      ceftazidime/avibactam and comparator (mostly carbapenem) was demonstrated for 30
      day all-cause mortality, late follow-up mortality and clinical response [relative
      risk (RR) 1.10, 95% CI 0.70-1.72, P = 0.69; RR 1.23, 95% CI 0.87-1.76, P = 0.25;
      RR 0.98, 95% CI 0.96-1.01, P = 0.21, respectively, without significant
      heterogeneity]. Higher microbiological response rate was demonstrated with
      ceftazidime/avibactam in patients with UTI (RR 1.14, 1.0-1.29, P = 0.05, I2 =
      51%). No significant difference in clinical response was demonstrated for
      patients with ceftazidime-resistant pathogens (RR 1.02, 95% CI 0.94-1.10, P =
      0.66, I2 = 0%). Results for other subgroups of resistant pathogens or hospital
      acquired infection were not available. Serious adverse events (SAEs) were
      significantly more common with ceftazidime/avibactam (RR 1.24, 95% CI 1.00-1.54,
      P = 0.05, I2 = 0%). Conclusions: Ceftazidime/avibactam is clinically and
      microbiologically as effective as carbapenems for treatment of infections in a
      setting of ~25% ESBL-carrying Enterobacteriaceae. Safety of the drug should be
      further evaluated owing to a higher rate of SAEs compared with carbapenems.
      Further studies should assess the drug's effectiveness in the treatment of
      carbapenemase-producing Enterobacteriaceae.

PMID- 29659838
TI  - Comparative methylome analysis of ICF patients identifies heterochromatin loci
      that require ZBTB24, CDCA7 and HELLS for their methylated state.
AB  - Alterations of DNA methylation landscapes and machinery are a hallmark of many
      human diseases. A prominent case is the ICF syndrome, a rare autosomal recessive
      immunological/neurological disorder diagnosed by the loss of DNA methylation at
      (peri)centromeric repeats and its associated chromosomal instability. It is
      caused by mutations in the de novo DNA methyltransferase DNMT3B in about half of
      the patients (ICF1). In the remainder, the striking identification of mutations
      in factors devoid of DNA methyltransferase activity, ZBTB24 (ICF2), CDCA7 (ICF3)
      or HELLS (ICF4), raised key questions about common or distinguishing DNA
      methylation alterations downstream of these mutations and hence, about the
      functional link between the four factors. Here, we established the first
      comparative methylation profiling in ICF patients with all four genotypes and we
      provide evidence that, despite unifying hypomethylation of pericentromeric
      repeats and a few common loci, methylation profiling clearly distinguished ICF1
      from ICF2, 3 and 4 patients. Using available genomic and epigenomic annotations
      to characterize regions prone to loss of DNA methylation downstream of ICF
      mutations, we found that ZBTB24, CDCA7 and HELLS mutations affect CpG-poor
      regions with heterochromatin features. Among these, we identified clusters of
      coding and non-coding genes mostly expressed in a monoallelic manner and
      implicated in neuronal development, consistent with the clinical spectrum of
      these patients' subgroups. Hence, beyond providing blood-based biomarkers of
      dysfunction of ICF factors, our comparative study unveiled new players to
      consider at certain heterochromatin regions of the human genome.

PMID- 29659837
TI  - Noonan syndrome-causing SHP2 mutants impair ERK-dependent chondrocyte
      differentiation during endochondral bone growth.
AB  - Growth retardation is a constant feature of Noonan syndrome (NS) but its
      physiopathology remains poorly understood. We previously reported that
      hyperactive NS-causing SHP2 mutants impair the systemic production of insulin
      like growth factor 1 (IGF1) through hyperactivation of the RAS/extracellular
      signal-regulated kinases (ERK) signalling pathway. Besides endocrine defects, a
      direct effect of these mutants on growth plate has not been explored, although
      recent studies have revealed an important physiological role for SHP2 in
      endochondral bone growth. We demonstrated that growth plate length was reduced in
      NS mice, mostly due to a shortening of the hypertrophic zone and to a lesser
      extent of the proliferating zone. These histological features were correlated
      with decreased expression of early chondrocyte differentiation markers, and with
      reduced alkaline phosphatase staining and activity, in NS murine primary
      chondrocytes. Although IGF1 treatment improved growth of NS mice, it did not
      fully reverse growth plate abnormalities, notably the decreased hypertrophic
      zone. In contrast, we documented a role of RAS/ERK hyperactivation at the growth
      plate level since 1) NS-causing SHP2 mutants enhance RAS/ERK activation in
      chondrocytes in vivo (NS mice) and in vitro (ATDC5 cells) and 2) inhibition of
      RAS/ERK hyperactivation by U0126 treatment alleviated growth plate abnormalities
      and enhanced chondrocyte differentiation. Similar effects were obtained by
      chronic treatment of NS mice with statins. In conclusion, we demonstrated that
      hyperactive NS-causing SHP2 mutants impair chondrocyte differentiation during
      endochondral bone growth through a local hyperactivation of the RAS/ERK
      signalling pathway, and that statin treatment may be a possible therapeutic
      approach in NS.

PMID- 29659840
TI  - What is the optimal target for the second arterial graft in patients undergoing
      coronary bypass surgery?
AB  - A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed was whether the anterolateral or the inferior
      wall served as a better location for the 2nd arterial graft in a 3-system
      coronary artery bypass grafting procedure. In total, more than 1800 papers were
      found, of which 6 represented the best evidence to answer the clinical question.
      All papers demonstrated equivalent early postoperative mortality and morbidity.
      The 3 largest studies comparing bilateral internal thoracic arteries showed no
      difference in perioperative mortality and morbidity regardless of whether the 2nd
      internal thoracic artery was used to graft the left or right system. One of these
      studies, however, showed significant survival benefit for the left-sided group at
      8 years, whereas another study showed a reduced patency of right internal
      thoracic arteries when grafted to the right coronary artery and when used in
      situ. One study compared radial grafts to the right- and left-sided targets and
      showed no difference in long-term patency. Another study also reported on the
      angiographic patency of right internal thoracic arteries. The authors noted a non
      significant increase in graft failure when non-left anterior descending arteries
      were grafted but no difference between circumflex or posterior descending
      arteries. All studies demonstrated similar or better mid- and long-term outcomes
      and patency rates when using the 2nd arterial graft to revascularize left-sided
      targets when compared with the right. However, all outcomes were similar when
      comparing non-left anterior descending left-sided targets with non-right coronary
      artery right-sided targets. Therefore, the right coronary artery itself should
      probably be avoided as the 2nd arterial target.

PMID- 29659839
TI  - Airway glycomic and allergic inflammatory consequences resulting from keratan
      sulfate galactose 6-O-sulfotransferase (CHST1) deficiency.
AB  - Siglec-F is a pro-apoptotic receptor on mouse eosinophils that recognizes 6'
      sulfated sialyl Lewis X and 6'-sulfated sialyl N-acetyl-lactosamine as well as
      multivalent sialyl N-acetyl-lactosamine structures on glycan arrays. We
      hypothesized that attenuation of the carbohydrate sulfotransferase 1 (CHST1) gene
      encoding keratan sulfate galactose 6-O-sulfotransferase, an enzyme likely
      required for 6'-sulfation of some of these putative Siglec-F glycan ligands,
      would result in decreased Siglec-F lung ligand levels and enhanced allergic
      eosinophilic airway inflammation. Tissue analysis detected CHST1 expression
      predominantly not only in parenchymal cells but not in airway epithelium, the
      latter being a location where Siglec-F ligands are located. Western blotting of
      lung extracts with Siglec-F-Fc fusion proteins detected ~500 kDa and ~200 kDa
      candidate Siglec-F ligands that were not appreciably altered in CHST1-/- lungs
      compared with normal mouse lungs. Characterization of the O-linked glycans of
      lung tissue and bronchoalveolar lavage fluid detected altered sialylation but
      minimal change in sulfation. Eosinophilic airway inflammation was induced in wild
      type (WT) and CHST1-/- mice via sensitization to ovalbumin (OVA) and repeated
      airway challenge. After OVA sensitization and challenge, Siglec-F ligands on
      airway cells, and numbers of eosinophils and neutrophils accumulating in the
      airways, both increased to a similar degree in WT and CHST1-/- mouse lungs, while
      macrophages and lymphocytes increased significantly more in CHST1-/- mouse airway
      compared with normal mouse lungs. Therefore, keratan sulfate galactose 6-O
      sulfotransferase does not contribute to the synthesis of glycan ligands for
      Siglec-F in the airways, although its absence results in exaggerated accumulation
      of airway macrophages and lymphocytes.

PMID- 29659841
TI  - Incidence and mortality from adverse effects of medical treatment in the UK, 1990
      2013: levels, trends, patterns and comparisons.
AB  - Objective: To present an update on incidence and mortality from adverse effects
      (AEs) of medical treatment in the UK, its four countries and nine English regions
      between 1990 and 2013. Design: Descriptive epidemiological study on AEs of
      medical treatment. AEs are shown as a single cause-of-injury category from the
      Global Burden of Disease (GBD) 2013 study. Data sources: The GBD 2013 interactive
      data visualisation tools 'Epi Visualisation' and 'GBD Compare'. Outcome measures:
      The means of incidence and mortality rates with 95% uncertainty intervals (UIs).
      The estimates are age-standardised. Results: Incidence rate was 175 and 176 cases
      per 100 000 men, 173 and 174 cases per 100 000 women in 1990 and 2013, in the UK
      (UI 170-180). The mortality from AEs declined from 1.33 deaths (UI 0.99-1.5) to
      0.92 deaths (UI 0.75-1.2) per 100 000 individuals in the UK between 1990 and 2013
      (30.8% change). Although mortality trends were descending in every region of the
      UK, they varied by geography and gender. Mortality rates in Scotland, North East
      England and West Midlands were highest. Mortality rates in South England and
      Northern Ireland were lowest. In 2013, age-specific mortality rates were higher
      in males in all 20 age groups compared with females. Conclusions: Despite gains
      in reducing mortality from AEs of medical treatment in the UK between 1990 and
      2013, the incidence of AEs remained the same. The results of this analysis
      suggest revising healthcare policies and programmes aimed to reduce incidence of
      AEs in the UK.

PMID- 29659843
TI  - A computed tomography-based planning tool for predicting difficulty of minimally
      invasive aortic valve replacement.
AB  - OBJECTIVES: Minimally invasive aortic valve replacement has proven its value over
      the last decade by its significant advancement and reduction in mortality,
      morbidity and admission time. However, minimally invasive aortic valve
      replacement is associated with some on-site difficulties such as limited aortic
      annulus exposure. Currently, computed tomography scans are used to evaluate the
      anatomical relationship among the intercostal spaces, ascending aorta and aortic
      valve prior to surgery. We hypothesized that quantitative measurements of access
      distance and access angle are associated with outcome and access difficulty.
      METHODS: We introduce a novel minimally invasive aortic valve replacement
      planning prototype that allows automatic measurements of access angle, access
      distance and aortic annulus dimensions. The prototype visualizes these
      measurements on the chest cage as ISO contours. The association of these measures
      with outcome parameters such as extracorporeal circulation time, aortic cross
      clamping time and access difficulty score was assessed. We included 14 patients
      who received a new valve by ministernotomy. RESULTS: The mean access angle was
      40.3 +/- 5.1 degrees . It was strongly associated with aortic cross-clamping time
      (Pearson correlation coefficient = 0.60, P = 0.02) and access difficulty score
      (Spearman's rank correlation coefficient = 0.57, P = 0.03). Access angles were
      significantly different between easy and difficult access groups (P = 0.03).
      There was no significant association between access distance and outcome
      parameters. CONCLUSIONS: Access angle is strongly associated with procedure
      complexity. The automated presentation of this measure suggests added value of
      the prototype in clinical practice.

PMID- 29659842
TI  - Insights into the pathogenesis of dominant retinitis pigmentosa associated with a
      D477G mutation in RPE65.
AB  - RPE65 is the essential trans-cis isomerase of the classical retinoid (visual)
      cycle. Mutations in RPE65 give rise to severe retinal dystrophies, most of which
      are associated with loss of protein function and recessive inheritance. The only
      known exception is a c.1430G>A (D477G) mutation that gives rise to dominant
      retinitis pigmentosa with delayed onset and choroidal and macular involvement.
      Position 477 is distant from functionally critical regions of RPE65. Hence, the
      mechanism of D477G pathogenicity remains unclear, although protein misfolding and
      aggregation mechanisms have been suggested. We characterized a D477G knock-in
      mouse model which exhibited mild age-dependent changes in retinal structure and
      function. Immunoblot analysis of protein extracts from the eyes of these knock-in
      mice demonstrated the presence of ubiquitinated RPE65 and reduced RPE65
      expression. We observed an accumulation of retinyl esters in the knock-in mice as
      well as a delay in rhodopsin regeneration kinetics and diminished
      electroretinography responses, indicative of RPE65 functional impairment induced
      by the D477G mutation in vivo. However, a cell line expressing D477G RPE65
      revealed protein expression levels, cellular localization and retinoid isomerase
      activity comparable to cells expressing wild-type protein. Structural analysis of
      an RPE65 chimera suggested that the D477G mutation does not perturb protein
      folding or tertiary structure. Instead, the mutation generates an aggregation
      prone surface that could induce cellular toxicity through abnormal complex
      formation as suggested by crystal packing analysis. These results indicate that a
      toxic gain-of-function induced by the D477G RPE65 substitution may play a role in
      the pathogenesis of this form of dominant retinitis pigmentosa.

PMID- 29659844
TI  - Surgery for acute infective endocarditis: epidemiological data from a Spanish
      nationwide hospital-based registry.
AB  - OBJECTIVES: Infective endocarditis (IE) is a serious and eventually lethal
      disease with rising incidence in the past couple of decades. The aim of this
      study was to evaluate the contemporary epidemiological trends of surgical
      endocarditis patients, to analyse the clinical outcomes and to study their
      profile, associated prognostic factors and costs. METHODS: This is a
      retrospective study of all patients admitted for IE in Spanish hospitals and
      discharged between 1 January 1997 and 31 December 2014. Data were extracted from
      the minimum basic data set of the National Surveillance System for Hospital Data
      in Spain provided by the Spanish Ministry of Health. Hospitalizations,
      comorbidities, outcomes and costs were analysed. RESULTS: In total, 34 399
      patients with IE were included; 15.7% of patients received surgical treatment and
      84.3% received medical treatment only. Surgical patients were mostly men (71.9%)
      and had a lower mean age (59.2 +/- 16.08 years) than the medical treatment group
      (P < 0.0001). Mortality among surgical patients showed a decreasing trend between
      1997 (32.0%) and 2014 (22.7%) and increased with age (47.6% in >=85 years of
      age). Length of hospital stay and the percentage of patients with organ
      dysfunction were also higher in this group. The cost of the surgical treatment
      group was higher and increased since 1997 (15 259.22 euros), remaining stable
      from 2010 (40 700 euros) (P < 0.0001). CONCLUSIONS: Surgical treatment in IE has
      trended upwards in Spain during the last 2 decades. Patients are getting older
      and more frequently experience organ dysfunction. Mortality ratio steadily
      declined without changes in the length of hospital stay.

PMID- 29659845
TI  - Data Resource Profile: Danish Conscription Registry Data (DCRD).

PMID- 29659846
TI  - Is administration of dual-antiplatelet therapy beneficial for patients following
      off-pump coronary artery bypass grafting?
AB  - A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed was whether administration of dual-antiplatelet
      therapy (DAPT) following off-pump coronary artery bypass grafting (OPCAB) would
      improve postoperative clinical outcomes or minimize the incidence of
      postoperative graft failure. In total, 101 papers were found using the reported
      search, 14 of which represented the best evidence to answer the clinical
      question. The authors, journal, date and country of publication, patient group
      studied, study type, relevant outcomes and results of these papers are tabulated.
      One meta-analysis and 3 randomized controlled trials showed that DAPT following
      OPCAB is associated with decreased incidence of saphenous vein graft occlusion.
      One randomized controlled trial and 4 observational studies showed no effect of
      DAPT on mortality following OPCAB, whereas 3 observational studies showed that
      DAPT decreased mortality. One meta-analysis and 4 observational studies showed
      that DAPT reduced the incidence of cardiac events following OPCAB. One randomized
      controlled trial and 4 observational studies showed that DAPT did not increase
      the incidence of major or minor bleeding complications following OPCAB. The
      results presented suggest that administration of DAPT in patients following OPCAB
      for at least 3 months improves saphenous vein graft patency and could be
      protective against recurrence of cardiac events, especially acute coronary
      syndrome, in comparison with aspirin monotherapy. The administration of DAPT
      following OPCAB is safe and is not associated with increased incidence of major
      or minor bleeding complications when compared with aspirin alone.

PMID- 29659847
TI  - Follicle growth and endocrine dynamics in women with spontaneous luteinized
      unruptured follicles versus ovulation.
AB  - STUDY QUESTION: Do growth patterns and endocrine profiles differ between
      ovulatory follicles (OvFs) and luteinized unruptured follicles (LUFs) in women?
      SUMMARY ANSWER: Growth rates, diameters and associated endocrine profiles
      differed between OvFs and LUFs in unstimulated cycles. WHAT IS KNOWN ALREADY: Two
      three waves of antral follicles develop during the menstrual cycle in ovulatory
      women of reproductive age, with the second or third wave terminating in
      ovulation. In contrast, some women can develop LUFs, where a preovulatory
      follicle fails to rupture and there is subsequent luteinization of the follicle
      wall. However, no study has compared OvFs and LUFs in unstimulated cycles. STUDY
      DESIGN, SIZE, DURATION: This retrospective observational study was conducted in
      56 healthy women of reproductive age (range: 19-41 years) and with a history of
      regular menstrual cycles. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants
      who met inclusion criteria were enrolled, as previously reported. Daily
      transvaginal ultrasonography was performed for one interovulatory interval (IOI)
      to measure the diameters of all follicles >2 mm. Blood samples were collected
      every 3 days during the IOI to measure serum concentrations of FSH, LH, estradiol
      and progesterone. MAIN RESULTS AND THE ROLE OF CHANCE: The interval from
      emergence to deviation (i.e. follicle selection) was shorter (P < 0.05) for LUFs
      compared to OvFs. However, the intervals from emergence to maximum diameter and
      deviation to maximum diameter were longer (P < 0.05) for LUFs compared to OvFs.
      Follicle deviation in LUFs occurred at a larger diameter (P < 0.05) compared to
      OvFs, and LUFs grew to larger (P < 0.0001) diameters compared to OvFs. Moreover,
      LUFs grew faster (P < 0.05) from emergence to deviation and from deviation to
      maximum diameter, compared to OvFs. LUFs were associated with low (P < 0.05)
      systemic LH levels at emergence and maximum diameter compared to OvFs. LUFs were
      also associated with low (P < 0.05) systemic FSH and high (P < 0.05) systemic
      progesterone at deviation and maximum diameter, respectively. Estradiol was
      higher (P < 0.05) at deviation and lower (P < 0.05) at maximum diameter for LUFs
      compared to OvFs. LIMITATIONS, REASONS FOR CAUTION: A 3-day interval of blood
      sampling for hormonal analyses was conducted, as a more frequent sampling
      interval was not considered acceptable by the study volunteers. A 3-day sampling
      interval did not allow characterization of acute changes in hormone production
      during the IOI. In addition, study visits were less frequent when LUFs persisted
      long after the expected day of the second ovulation of the IOI. WIDER
      IMPLICATIONS OF THE FINDINGS: Information about the growth and endocrine dynamics
      of OvFs and LUFs developing in unstimulated cycles in women may be applied to the
      early detection of LUF-associated anovulatory infertility and clinical management
      of women with this condition. STUDY FUNDING/COMPETING INTEREST(S): No external
      funding sources were used for this study. The authors have no conflicts of
      interest in publishing this manuscript. TRIAL REGISTRATION NUMBER:
      ClinicalTrials.gov Identifier: NCT01389141.

PMID- 29659849
TI  - Corrigendum to: 'Onchocerciasis: the beginning of the end'.

PMID- 29659848
TI  - Why after 50 years of effective contraception do we still have unintended
      pregnancy? A European perspective.
AB  - Unintended pregnancy is a public health concern throughout Europe. There is no
      common definition and no standard way to measure unintended pregnancy.
      Identifying unintended births is difficult and prevalence estimates vary
      depending on how and when the question is asked. Abortion rates are not a proxy
      and are themselves notoriously inaccurate. An estimated 34% (in Western Europe)
      to 54% (in Eastern Europe) of pregnancies are unintended. The determinants of
      unintended pregnancy are the length of the reproductive span and exposure to the
      risk of conception; the desired number of children and contraceptive use and
      effectiveness. The age of sexual debut fell during the 20th century in Europe to
      between 15 and 18 years of age. Mean age at first birth for women is now over 30
      years in most European countries and most couples want no more than two children.
      Thus most couples must use contraception perfectly for many years in order to
      avoid unintended pregnancy. Use of effective contraception is high throughout
      most of Europe but there is scope, through better provision of sexual health
      services, better formal sex education and better training of providers, to
      increase the uptake of the most effective contraceptives and improve use of all
      methods. For individual women unintended pregnancy can be a disaster and recourse
      to induced abortion should be freely available.

PMID- 29659850
TI  - Orthologues of Streptococcus pyogenes nuclease A (SpnA) and Streptococcal 5'
      nucleotidase A (S5nA) found in Streptococcus iniae.
AB  - Streptococcus pyogenes nuclease A (SpnA) and streptococcal 5' nucleosidase A
      (S5nA) are two recently described virulence factors from the human pathogen S.
      pyogenes. In vitro studies have shown that SpnA is a nuclease that cleaves ssDNA
      and dsDNA, including the DNA backbone of neutrophil extracellular traps. S5nA was
      shown to hydrolyse AMP and ADP, but not ATP, to generate the immunomodulatory
      molecule adenosine. S5nA also generates the macrophage-toxic deoxyadenosine from
      dAMP. However, detailed in vivo studies of the two enzymes have been hampered by
      difficulties with using current animal models for this exclusive human pathogen.
      Here we report the identification of two novel enzymes from the fish pathogen
      Streptococcus iniae that show similarities to SpnA and S5nA in amino acid
      sequence, protein domain structure and biochemical properties. We propose that
      SpnAi and S5nAi are orthologues of the S. pyogenes enzymes, providing a rationale
      to analyse the in vivo function of the two enzymes using a S. iniae-zebrafish
      infection model.

PMID- 29659851
TI  - Causes of death at the University of Ghana Hospital in Accra-a 37-year review
      (1979-2015).
AB  - Background: An analysis of the causes of death in developing countries is needed
      to improve healthcare delivery. The aim of this study was to conduct a
      descriptive analysis of the causes of death at the University of Ghana Hospital
      from 1979 to 2015. Methods: Data were extracted from the electronic database of
      the University of Ghana Hospital. Diseases were grouped into three broad groups
      of causes of death as per the Global Burden of Disease cause list, with some
      diseases of epidemiological importance outlined and analysed by age, gender and
      time in years. Results: Of 3263 deaths, almost 60% were caused by non
      communicable diseases (NCDs) that consisted of cancers, diabetes mellitus,
      cardiovascular diseases and other systemic conditions. Deaths by malaria,
      tuberculosis, diarrhoeal diseases and immunizable childhood diseases declined
      over the years while deaths from NCDs increased. The majority of cases of NCDs
      were due to cardiovascular disorders. Conclusions: The study suggests that Ghana
      has a double burden of disease with predominantly NCDs from cardiovascular
      diseases, metabolic disorders and cancers. Although malaria and other childhood
      related illnesses have declined significantly, human immunodeficiency virus is
      fuelling the communicable disease mortalities. There is an urgent need to scale
      up NCD control interventions while strengthening communicable disease control.

PMID- 29659852
TI  - Determinants of primary healthcare seeking behaviours for children during the
      first 18 months of life in Benin.
AB  - Background: Primary healthcare is a key element of management of childhood
      illness in Africa. The objectives were to identify primary care seeking
      determinants among infants and young children up to 18 mo in a birth cohort from
      Benin. Methods: From 2007 to 2009 in Benin, a birth cohort was followed until the
      age of 18 mo in three health centres. Multilevel Poisson regression models were
      fitted to identify the factors related to the monthly number of consultations.
      Maternal and newborn characteristics and infant general health parameters were
      considered. Results: A total of 566 children were followed. On average, 0.46
      consultations per month per child were recorded. The number of consultations was
      significantly lower after the first 6 mo of life (p<0.001). A distance >1000 m
      was associated with fewer consultations (p=0.01). Primiparity was significantly
      associated with higher care seeking (relative risk 1.17 [95% CI 1.05 to 1.30],
      p<0.01). No child characteristics at birth were significantly associated with the
      number of consultations (all p>0.16). Conclusions: Development of health
      structures and improvement of access remain important goals for strengthening of
      the primary care health system. Studying factors of care seeking behaviour, like
      parity, can help to identify women more prone to seek care for their child during
      the first year of life.

PMID- 29659853
TI  - In vitro activity of ceftaroline against clinical Staphylococcus aureus isolates
      collected during a national survey conducted in Belgian hospitals.

PMID- 29659854
TI  - Prospective Evaluation of Operating Room Inefficiency.
AB  - Previously, they identified that 60 per cent of their facility's total operative
      time is nonoperative. They performed a review of their operating room to
      determine where inefficiencies exist in nonoperative time. Live video of
      operations performed in a burn operating room from June 23, 2017 to August 16,
      2017 was prospectively reviewed. Preparation (end of induction to procedure
      start) and turnover (patient out of room to next patient in room) were divided
      into the following activities: 1) Preparation: remove dressing, position patient,
      clean patient, drape patient, and 2) Turnover: clean operating room, scrub tray
      setup, anesthesia setup. Ideal preparation time was calculated as the sum of time
      needed to perform preparation activities consecutively. Ideal turnover time was
      calculated as the sum of time needed to clean the operating room and to set up
      either the scrub tray or anesthesia (the larger of the two times as these can be
      done in parallel). They reviewed 101 consecutive operations. An average of 2.4 +/
      0.8 cases per day were performed. Ideal preparation and turnover time were 16.6
      and 30.1 minutes, a 38.3 and 32.5 per cent reduction compared with actual times.
      Attending surgeon presence in the operating room within 10 minutes of a patient's
      arrival was found to significantly decrease time to incision by 33 per cent (52.7
      +/- 14.3 minutes down to 35.7 +/- 20.4, P < .0001). A reduction in preparation
      and turnover time could save $1.02 million and generate $1.76 million in
      additional revenue annually. Reducing preparation and turnover to ideal times
      could increase caseload to 4 per day, leading to millions of dollars of savings
      annually.

PMID- 29659856
TI  - Integration of physical abuse clinical decision support into the electronic
      health record at a Tertiary Care Children's Hospital.
AB  - Objective: To evaluate the effect of a previously validated electronic health
      record-based child abuse trigger system on physician compliance with clinical
      guidelines for evaluation of physical abuse. Methods: A randomized controlled
      trial (RCT) with comparison to a preintervention group was performed. RCT
      experimental subjects' providers received alerts with a direct link to a physical
      abuse-specific order set. RCT-control subjects' providers had no alerts, but
      could manually search for the order set. Preintervention subjects' providers had
      neither alerts nor access to the order set. Compliance with clinical guidelines
      was calculated. Results: Ninety-nine preintervention subjects and 130 RCT
      subjects (73 RCT-experimental and 57 RCT-control) met criteria to undergo a
      physical abuse evaluation. Full compliance with clinical guidelines was 84% pre
      intervention, 86% in RCT-control group, and 89% in RCT-experimental group. The
      physical abuse order set was used 43 times during the 7-month RCT. When the abuse
      order set was used, full compliance was 100%. The proportion of cases in which
      there was partial compliance decreased from 10% to 3% once the order set became
      available (P = .04). Male gender, having >10 years of experience and completion
      of a pediatric emergency medicine fellowship were associated with increased
      compliance. Discussion/Conclusion: A child abuse clinical decision support system
      comprised of a trigger system, alerts and a physical abuse order set was quickly
      accepted into clinical practice. Use of the physical abuse order set always
      resulted in full compliance with clinical guidelines. Given the high baseline
      compliance at our site, evaluation of this alert system in hospitals with lower
      baseline compliance rates will be more valuable in assessing the efficacy in
      adherence to clinical guidelines for the evaluation of suspected child abuse.

PMID- 29659855
TI  - Mobile colistin resistance gene mcr-5 in porcine Aeromonas hydrophila.
AB  - Objectives: To characterize the mobile colistin resistance gene mcr-5 in
      Aeromonas hydrophila from backyard pigs in rural areas of China. Methods: Pig
      faecal samples from 194 households were directly tested for the presence of mcr-5
      by PCR assay and the phenotypic antimicrobial susceptibility profiles of the mcr
      5-positive isolates were determined using the broth dilution method. The genomic
      location and transferability of mcr-5 were analysed by S1-PFGE with Southern
      blotting and DNA hybridization, and natural transformation, respectively. One
      strain isolated from an mcr-5-positive sample was subjected to WGS and the
      stability of the mcr-5-harbouring plasmid over successive generations was
      examined by subculturing. Results: One mcr-5-positive A. hydrophila isolate
      showing resistance, with a colistin MIC of 4 mg/L, was isolated from a backyard
      pig faecal sample. mcr-5 was located on a 7915 bp plasmid designated pI064-2,
      which could naturally transform into a colistin-susceptible A. hydrophila strain
      of porcine origin and mediated colistin resistance in both the original isolate
      and its transformants. The plasmid backbone (3790 bp) of pI064-2 showed 81%
      nucleotide sequence identity to the corresponding region of the ColE2-type
      plasmid pAsa1 from Aeromonas salmonicida, while similar replication primases are
      widely distributed among aeromonads, Enterobacteriaceae and Pseudomonas species.
      Conclusions: To the best of our knowledge, this is the first identification of
      the novel colistin resistance gene mcr-5 in an A. hydrophila isolate from the
      faeces of a backyard pig. mcr-5 is expected to be able to disseminate among
      different bacterial species and genera.

PMID- 29659857
TI  - Evaluation of a recommender app for apps for the treatment of depression and
      anxiety: an analysis of longitudinal user engagement.
AB  - Objective: While depression and anxiety are common mental health issues, only a
      small segment of the population has access to standard one-on-one treatment. The
      use of smartphone apps can fill this gap. An app recommender system may help
      improve user engagement of these apps and eventually symptoms. Methods:
      IntelliCare was a suite of apps for depression and anxiety, with a Hub app that
      provided app recommendations aiming to increase user engagement. This study
      captured the records of 8057 users of 12 apps. We measured overall engagement and
      app-specific usage longitudinally by the number of weekly app sessions
      ("loyalty") and the number of days with app usage ("regularity") over 16 weeks.
      Hub and non-Hub users were compared using zero-inflated Poisson regression for
      loyalty, linear regression for regularity, and Cox regression for engagement
      duration. Adjusted analyses were performed in 4561 users for whom we had baseline
      characteristics. Impact of Hub recommendations was assessed using the same
      approach. Results: When compared to non-Hub users in adjusted analyses, Hub users
      had a lower risk of discontinuing IntelliCare (hazard ratio = 0.67, 95% CI, 0.62
      0.71), higher loyalty (2- to 5-fold), and higher regularity (0.1-0.4 day/week
      greater). Among Hub users, Hub recommendations increased app-specific loyalty and
      regularity in all 12 apps. Discussion/Conclusion: Centralized app recommendations
      increase overall user engagement of the apps, as well as app-specific usage.
      Further studies relating app usage to symptoms can validate that such a
      recommender improves clinical benefits and does so at scale.

PMID- 29659858
TI  - ZAAPS programme results for 2016: an activity and spectrum analysis of linezolid
      using clinical isolates from medical centres in 42 countries.
AB  - Objectives: To report the linezolid activity, resistance mechanisms and
      epidemiological typing of selected isolates observed during the 2016 Zyvox(r)
      Annual Appraisal of Potency and Spectrum (ZAAPS) programme. Methods: A total of
      8325 organisms were consecutively collected from 76 centres in 42 countries
      (excluding the USA). Broth microdilution susceptibility testing was performed and
      isolates displaying linezolid MICs of >=4 mg/L were molecularly characterized.
      Results: Linezolid inhibited 99.8% of all Gram-positive pathogens at the
      respective susceptible breakpoints and showed a modal MIC of 1 mg/L, except for
      CoNS, for which the modal MIC result was 0.5 mg/L. Among isolates displaying
      linezolid MICs of >=4 mg/L, one Staphylococcus aureus (linezolid MIC of 4 mg/L)
      harboured cfr and belonged to ST72, while four CoNS (MICs of 16-32 mg/L; ST2)
      showed drug target alterations. Two Enterococcus faecium (ST117) from a single
      site in Rome were linezolid non-susceptible (MICs of 8 mg/L) and had G2576T
      mutations. Eight linezolid-non-susceptible Enterococcus faecalis (MICs of 4 mg/L;
      4 sites in 4 countries; ST256, ST480, ST766 and ST775) carried optrA and isolates
      carrying optrA from the same medical centre were genetically related. One
      Streptococcus gallolyticus (MIC of 4 mg/L) and one Streptococcus mitis (MIC of 16
      mg/L) carried optrA and G2576T mutations, respectively. Conclusions: These
      results document the continued long-term in vitro potency of linezolid.
      Alterations in the 23S rRNA and/or L3/L4 proteins remain the main oxazolidinone
      resistance mechanisms in E. faecium and CoNS, whereas optrA emerged as the sole
      mechanism in E. faecalis. Surveillance and infection control will be important
      strategies to detect optrA and prevent it from disseminating.

PMID- 29659860
TI  - Analyzing the effects of instillation volume on intravesical delivery using
      biphasic solute transport in a deformable geometry.
AB  - Ailments of the bladder are often treated via intravesical delivery-direct
      application of therapeutic into the bladder through a catheter. This technique is
      employed hundreds of thousands of times every year, but protocol development has
      largely been limited to empirical determination. Furthermore, the numerical
      analyses of intravesical delivery performed to date have been restricted to
      static geometries and have not accounted for bladder deformation. This study uses
      a finite element analysis approach with biphasic solute transport to investigate
      several parameters pertinent to intravesical delivery including solute
      concentration, solute transport properties and instillation volume. The volume of
      instillation was found to have a substantial impact on the exposure of solute to
      the deeper muscle layers of the bladder, which are typically more difficult to
      reach. Indeed, increasing the instillation volume from 50-100 ml raised the
      muscle solute exposure as a percentage of overall bladder exposure from 60-70%
      with higher levels achieved for larger instillation volumes. Similar increases
      were not seen for changes in solute concentration or solute transport properties.
      These results indicate the role that instillation volume may play in targeting
      particular layers of the bladder during an intravesical delivery.

PMID- 29659859
TI  - Seroprevalence of Toxoplasma gondii and Neospora caninum infection in sheep,
      goats, and fallow deer farmed on the same area.
AB  - Toxoplasma gondii and Neospora caninum are coccidian parasites with a global
      distribution that cause reproductive failure and production losses in livestock.
      The seroprevalence of both parasite species in ruminants and Cervidae has been
      investigated worldwide and found to vary greatly. Studies carried out on mixed
      flocks with 3 ruminant species (sheep, goats, and fallow deer) living under the
      same conditions are excellent models for identifying any differences in the rate
      of infection with the 2 parasites between the animal species. Additionally, the
      species used in the present study differ in their feeding categories: grazers,
      browsers, and intermediate feeders. The aim of the study is to identify any
      variation in the prevalence of the 2 parasites in mixed flocks and to identify
      any possible relationships with food choice. The seroprevalence against T. gondii
      and N. caninum in 167 captive fallow deer, 64 sheep, and 39 goats were detected
      using commercially available ELISA. The seroprevalence for T. gondii achieved 10%
      in fallow deer, 21% in goats, and 47% in sheep. The seroprevalence for N. caninum
      achieved 13% in sheep and fallow deer and 21% in goats. Overall, 53% of the
      sheep, 33% of the goats, and 22% of the fallow deer were seropositive for both
      infections. Coinfection of T. gondii and N. caninum was detected in 6% of sheep,
      8% of goats, and 2% of fallow deer. Statistical analyses of the seroprevalence
      levels observed between 2 parasites for each animal species revealed that only
      the results obtained for sheep were significant (P < 0.01). Additionally, the
      differences in the seroprevalence levels for T. gondii between sheep and goats
      and between sheep and fallow deer were statistically significant (P < 0.01). The
      results of the N. caninum seroprevalence levels observed among animal species
      were not significant. Although the variations in susceptibility to T. gondii and
      N. caninum infections demonstrated by the examined animals may affect the
      differences in seropositivity, these appear to be related to the feeding habits
      of the animal species. Therefore, the risk of infection by agents found close to
      the ground, such as coccidian oocysts, varies. Sheep as grazers are at a greater
      risk of infection by T. gondii than goats and fallow deer.

PMID- 29659861
TI  - In vitro activity of imipenem/relebactam against Gram-negative ESKAPE pathogens
      isolated in 17 European countries: 2015 SMART surveillance programme.
AB  - Objectives: Relebactam is an inhibitor of class A beta-lactamases, including KPC
      beta-lactamases, and class C beta-lactamases, and is currently under clinical
      development in combination with imipenem. The objective of the current study was
      to evaluate the in vitro activity of imipenem/relebactam against Gram-negative
      ESKAPE pathogens (Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas
      aeruginosa and Enterobacter spp.) submitted by clinical laboratories in 17
      European countries to the Study for Monitoring Antimicrobial Resistance Trends
      (SMART) global surveillance programme in 2015. Methods: MICs were determined
      using the CLSI standard broth microdilution method and interpreted using EUCAST
      clinical breakpoints. Relebactam was tested at a fixed concentration of 4 mg/L in
      combination with doubling dilutions of imipenem. Imipenem/relebactam MICs were
      interpreted using breakpoints for imipenem. Results: Rates of susceptibility to
      imipenem and imipenem/relebactam for isolates of P. aeruginosa (n = 1705), K.
      pneumoniae (n = 1591) and Enterobacter spp. (n = 772) were 72.0/94.7%, 88.7/94.8%
      and 95.6/96.8%, respectively. Relebactam restored imipenem susceptibility to
      81.1%, 54.2% and 26.5% of imipenem-non-susceptible isolates of P. aeruginosa (n =
      477), K. pneumoniae (n = 179) and Enterobacter spp. (n = 34). Most
      imipenem/relebactam-non-susceptible isolates carried MBLs, OXA-48 or GES
      carbapenemases. Relebactam did not increase the number of isolates of A.
      baumannii (n = 486) susceptible to imipenem. Conclusions: Relebactam restored
      susceptibility to imipenem for the majority of imipenem-non-susceptible isolates
      of P. aeruginosa and K. pneumoniae tested as well as some isolates of imipenem
      non-susceptible Enterobacter spp. Based on our results, imipenem/relebactam
      appears to be a promising therapeutic option for treating patients with
      infections caused by antimicrobial-resistant Gram-negative bacilli.

PMID- 29659863
TI  - Frequent use of emergency departments by older people: a comparative cohort study
      of characteristics and outcomes.
AB  - Objective: To characterise older people who frequently use emergency departments
      (EDs) and compare patient outcomes with older non-frequent ED attenders. Design:
      Retrospective comparative cohort study. Logistic regression modelling of patient
      characteristics and health service usage, comparing older frequent ED attenders
      (>=4 ED attendances in 12 months) to non-frequent ED attenders. Setting: Three
      Australian public hospital EDs, with a total of 143 327 emergency attendances in
      the 12 months. Participants: People aged >=65 years attending the ED in financial
      year 2013/2014. Main Outcome Measures: The primary outcome was frequent ED use;
      secondary outcomes were ED length of stay, discharge destination from ED,
      hospital length of stay, re-presentation within 48 h, hospital readmission within
      30 days and in-hospital mortality. Results: Five percent of older people were
      frequent attenders (n = 1046/21 073), accounting for 16.9% (n = 5469/32 282) of
      all attendances by older people. Frequent ED attenders were more likely to be
      male, aged 75-84 years, arrive by ambulance and have a diagnosis relating to
      chronic illness. Frequent attenders stayed 0.4 h longer in ED (P < 0.001), were
      more likely to be admitted to hospital (69.2% vs 67.2%; P = 0.004), and had a 1
      day longer hospital stay (P < 0.001). In-hospital mortality for older frequent ED
      attenders was double that of non-frequent attenders (7.0% vs 3.2%, P < 0.001)
      over 12 months. Conclusions: Older frequent ED attenders had more chronic disease
      and care needs requiring hospital admission than non-frequent attenders. A new
      approach to care planning and coordination is recommended, to optimise the
      patient journey and improve outcomes.

PMID- 29659862
TI  - Effects of hormonal growth promotants on beef quality: a meta-analysis.
AB  - Benefits of hormonal growth promotants (HGPs) include production efficiency,
      profit, and reduced environmental effects for beef cattle. Questions remain about
      effects of HGP on beef quality, particularly on measures of toughness such as
      Warner-Bratzler shear force (WBSF), tenderness, and other taste-panel attributes
      of beef. The objective of this meta-analysis was to assess the effects of HGP on
      beef quality using the results of randomized controlled trials identified from 3
      searched databases. Thirty-one experiments with 181 treatment comparisons were
      used to evaluate the effects of HGP on WBSF and sensory measures of beef quality.
      Experiments varied in design, used many different hormonal treatments and
      combinations, which were single or repeated, in different breeds and sex groups
      of cattle, with or without electrical stimulation, and with different lengths of
      time on feed and beef aging. The effects of multiple treatment comparisons in
      experiments were evaluated using robust regression models and compared to Knapp
      Hartung and permutation meta-analytical methods. Increased WBSF was associated
      with HGP treatment. Use of multiple HGP implants was associated with an increase
      in WBSF of 0.248 kg (95% CI = 0.203 to 0.292). Effects of a single implant only
      increased WBSF by 0.176 kg (95% CI = 0.109 to 0.242). Aging of beef did not alter
      the association of HGP with increased WBSF (P = 0.105); however, the point
      direction was toward a reduced effect with aging (standardized mean difference
      [SMD] = -0.005 per day aged). While aging lowered WBSF, it did not reduce the SMD
      between HGP treatment and reference groups. Comparisons using trenbolone acetate
      did not differ in WBSF from those using other implants (P > 0.15). The findings
      on sensory panel tenderness differ from those using WBSF as HGP treatment was not
      associated with reduced tenderness (P > 0.3) and multiple HGP treatments improved
      tenderness (SMD = 0.468) compared to a single implant. Further, juiciness,
      flavor, and connective tissue were not associated with HGP use, whereas there was
      a marked 5.5-point decrease in the Meat Standards Australia meat quality 4 score,
      albeit with limited experiments. In general, the true variance of experiments,
      tau2 (tau2) was low (<0.1), but heterogeneity, I2 was high (>50%) indicating that
      much of the variance was due to factors other than measurement error. More
      targeted studies on the role of HGP in influencing beef quality are needed.

PMID- 29659864
TI  - Type VI collagen alpha1 chain polypeptide in non-triple helical form is an
      alternative gene product of COL6A1.
AB  - Expression of type IV collagen alpha1 chain in non-triple helical form, NTH
      alpha1(IV), is observed in cultured human cells, human placenta and rabbit
      tissues. Biological functions of NTH alpha1(IV) are most likely to be distinct
      from type IV collagen, since their biochemical characteristics are quite
      different. To explore the biological functions of NTH alpha1(IV), we prepared
      some anti-NTH alpha1(IV) antibodies. In the course of characterization of these
      antibodies, one antibody, #141, bound to a polypeptide of 140 kDa in size in
      addition to NTH alpha1(IV). In this study, we show evidence that the 140 kDa
      polypeptide is a novel non-triple helical polypeptide of type VI collagen alpha1
      chain encoded by COL6A1, or NTH alpha1(VI). Expression of NTH alpha1(VI) is
      observed in supernatants of several human cancer cell lines, suggesting that the
      NTH alpha1(VI) might be involved in tumourigenesis. Reactivity with lectins
      indicates that sugar chains of NTH alpha1(VI) are different from those of the
      alpha1(VI) chain in triple helical form of type VI collagen, suggesting a
      synthetic mechanism and a mode of action of NTH alpha1(VI) is different from type
      VI collagen.

PMID- 29659866
TI  - Corrigendum to: A proposed fractional-order Gompertz model and its application to
      tumour growth data.

PMID- 29659865
TI  - Effects of a multielement trace mineral injection and vitamin E supplementation
      on performance, carcass characteristics, and color stability of strip steaks from
      feedlot heifers.
AB  - The objective was to evaluate the interaction of a trace mineral (TM) injection
      (Multimin 90) and a supranutritional concentration of dietary vitamin E (VITE) on
      performance, carcass characteristics, and color stability of strip steaks from
      feedlot heifers. Prior to trial initiation, Angus * Simmental cross heifers (N =
      48) were managed on a common diet supplemented to meet the NRC recommendations.
      Heifers were stratified by BW and allotted to a 2 * 2 factorial arrangement: 1)
      no supplemental vitamin E and saline injection (CONT + SAL), 2) 1,000 IU vitamin
      E.heifer-1.d-1 and saline injection (VITE + SAL), 3) no supplemental vitamin E
      and TM injection (CONT + MM), or 4) vitamin E and TM injection (VITE + MM). Trace
      mineral injection contained 15, 10, 5, and 60 mg/mL of Cu, Mn, Se, and Zn,
      respectively, and TM injection or saline injection (1 mL/68 kg BW) were given on
      day 0 of the 89-d finishing period. All heifers were fed a common diet containing
      a basal concentration of 19.8 IU/kg DM vitamin E. Heifers were slaughtered and
      loins sections were collected. Strip steaks were cut and placed in overwrap trays
      for evaluation of color stability for 16 d. Data were analyzed using the MIXED
      procedure of SAS. Color stability data were analyzed as repeated measures.
      Neither TM injection nor VITE had an effect on final BW, DMI, or G:F (P >= 0.12).
      There was a tendency (P = 0.09) for TM injection to increase ADG. A tendency (P =
      0.08) was observed for TM injection to increase DMI of heifers receiving
      supranutritional VITE. Trace mineral injection and VITE had no effect on HCW,
      yield grade, 12th-rib backfat thickness, or ribeye area (P >= 0.34). Marbling
      scores tended to increase (P = 0.08) in VITE heifers compared with control-fed
      heifers. Vitamin E supplementation decreased final lipid oxidation (1.00 vs. 1.97
      ug malondialdehyde/g fat, P = 0.03) and total visual discoloration (15.82% vs.
      33.96%, P = 0.04) of steaks compared with steaks from nonsupplemented heifers.
      Heifers fed supranutritional VITE produced steaks that maintained retail color
      longer shown by lower hue angle values (38.17 degrees  vs. 38.66 degrees , P <
      0.01) than nonsupplemented heifers. A TM injection * vitamin E * day interaction
      (P < 0.01) revealed by day 16 steaks from the CONT + MM heifers exhibited greater
      discoloration than VITE + SAL and VITE + MM steaks with CONT + SAL intermediate.
      Overall, VITE improved color stability and TM injection appeared to increase
      discoloration of strip steaks from feedlot heifers after day 14 of display.

PMID- 29659867
TI  - Gastric Emptying Impacts the Timing of Meal Glucose Peak in Subjects With
      Uncomplicated Type 1 Diabetes.
AB  - Context: Diabetes mellitus is associated with gastrointestinal (GI) motility
      dysfunction, ranging from delayed to accelerated gastric emptying (GE).
      Objective: To evaluate GE in patients with type 1 diabetes mellitus (T1DM)
      without chronic complications and to investigate its relation with postprandial
      glucose and GI hormone responses. Design: Cross-sectional study.
      Setting/Participants: Forty-two patients with T1DM free of chronic complications
      referred to Federico II University and 31 healthy controls similar for age, sex,
      and body mass index. Interventions/Main Outcome Measures: GE was assessed by
      using the 13C-octanoate breath test with a standardized solid meal. During the
      meal, plasma glucose, ghrelin, and glucagon-like peptide 1 (GLP-1) responses were
      assessed, and GI symptoms were evaluated by a specific questionnaire. Results:
      Patients with T1DM showed a significantly slower GE half-emptying time (GE t1/2)
      (113 +/- 34 minutes) than did controls (89 +/- 17 minutes; P < 0.001). Thirty-six
      percent of T1DM showed a delayed GE (t1/2 > 120 minutes), whereas all controls
      showed a normal GE. When patients with T1DM were stratified according to GE t1/2,
      postmeal glucose response was significantly different between those with delayed
      and those with normal GE (P = 0.013). In particular, patients with T1DM and
      delayed GE showed a significantly longer mean time to peak glucose than did
      patients with normal GE (P = 0.004). In addition, GE t1/2 was an independent
      predictor of the time to peak glucose (beta = 0.329; P = 0.025). GLP-1 and
      ghrelin responses to the test meal, as well as the prevalence of GI symptoms,
      were similar between patients with T1DM and controls and between patients with
      T1DM with normal GE and those with delayed GE. Conclusions: Delayed GE time is
      associated with a longer time to peak glucose. GE evaluation could be useful for
      individualizing the timing of preprandial insulin bolus in patients with T1DM.

PMID- 29659868
TI  - Automatic population of eMeasurements from EHR systems for inpatient falls.
AB  - Objective: Representing nursing data sets in a standard way will help to
      facilitate sharing relevant information across settings. We aimed to populate
      nursing process and outcome metrics with electronic health record (EHR) data and
      then compare the results with event reporting systems. Methods: We used the
      "eMeasure" development process of the National Quality Forum adopted by the
      American Nurses Association. We used operational definitions of quality measures
      from the American Nurses Association and the US Institute for Healthcare
      Improvement and employed concept mapping of local data elements to 2 controlled
      vocabularies to define a standard data dictionary: (1) Logical Observation
      Identifiers Names and Codes and (2) International Classification for Nursing
      Practice. We assessed feasibility using the nursing data set of 7829 and 8199
      patients from 2 general hospitals with different EHR systems. Using inpatient
      falls as a use case, we compared the populated measures with results from the
      event reporting systems. Results: We identified 17 care components and 118 unique
      concepts and matched them with data elements in the EHRs. Including suboptimal
      mapping, 98% of the assessment concepts mapped to Logical Observation Identifiers
      Names and Codes and 52.9% of intervention concepts mapped to International
      Classification for Nursing Practice. While not all process indicators were
      available from event reporting systems, we successfully populated 9 fall
      prevention process indicators and the fall rate outcome indicator from the 2
      EHRs. We were unable to populate the falls with an injury rate indicator.
      Conclusions: EHR data can populate fall prevention process measure metrics and at
      least one inpatient fall prevention outcome metric.

PMID- 29659869
TI  - Comment on: MIC-based dose adjustment: facts and fables.

PMID- 29659870
TI  - Corrigendum.

PMID- 29659871
TI  - Rare Variants in the Gene ALPL That Cause Hypophosphatasia Are Strongly
      Associated With Ovarian and Uterine Disorders.
AB  - Context: Mutations in alkaline phosphatase (AlkP), liver/bone/kidney (ALPL),
      which encodes tissue-nonspecific isozyme AlkP, cause hypophosphatasia (HPP). HPP
      is suspected by a low-serum AlkP. We hypothesized that some patients with bone or
      dental disease have undiagnosed HPP, caused by ALPL variants. Objective: Our
      objective was to discover the prevalence of these gene variants in the Vanderbilt
      University DNA Biobank (BioVU) and to assess phenotypic associations. Design: We
      identified subjects in BioVU, a repository of DNA, that had at least one of three
      known, rare HPP disease-causing variants in ALPL: rs199669988, rs121918007,
      and/or rs121918002. To evaluate for phenotypic associations, we conducted a
      sequential phenome-wide association study of ALPL variants and then performed a
      de-identified manual record review to refine the phenotype. Results: Out of
      25,822 genotyped individuals, we identified 52 women and 53 men with HPP disease
      causing variants in ALPL, 7/1000. None had a clinical diagnosis of HPP. For
      patients with ALPL variants, the average serum AlkP levels were in the lower
      range of normal or lower. Forty percent of men and 62% of women had documented
      bone and/or dental disease, compatible with the diagnosis of HPP. Forty percent
      of the female patients had ovarian pathology or other gynecological abnormalities
      compared with 15% seen in controls. Conclusions: Variants in the ALPL gene cause
      bone and dental disease in patients with and without the standard biomarker, low
      plasma AlkP. ALPL gene variants are more prevalent than currently reported and
      underdiagnosed. Gynecologic disease appears to be associated with HPP-causing
      variants in ALPL.

PMID- 29659872
TI  - Evaluating the microbiome of two sampling locations in the nasal cavity of cattle
      with bovine respiratory disease complex (BRDC).
AB  - Bovine respiratory disease complex (BRDC) is a multifactor disease, and disease
      incidence may be associated with an animal's commensal bacterial populations
      (microbiome) in the upper nasal cavity. Identifying these commensal bacterial
      populations in the upper nasal cavity may help us to understand the impact of the
      microbiome on incidence of BRDC in cattle. Various sampling techniques have
      previously been utilized to evaluate the microbiome of different locations of the
      upper nasal cavity in cattle. Therefore, our objective was to determine whether
      bacterial populations of the nasal cavity vary based on these sampling locations.
      Two common sampling techniques were evaluated, including 6-inch nasal swabs and
      deep nasopharyngeal swabs. Nasal swabs from calves were collected when the animal
      was diagnosed with BRDC after weaning in the feedlot in addition to collection of
      samples from asymptomatic cohorts. Samples were pooled in groups based on year
      the animal was in the feedlot (2015 or 2016), when the animal was diagnosed with
      BRDC (1 to 5 weeks after weaning), type of sample (6-inch nasal swab or deep
      nasopharyngeal swab), and health status (diagnosis with BRDC or control).
      Variable regions 1 through 3 along the 16S rRNA gene were amplified by PCR and
      sequenced using next-generation sequencing (Illumina MiSeq) for identification of
      the bacterial taxa present. Overall, sampling site did not consistently influence
      diversity of the bacterial populations of the upper nasal cavity. However, the
      effect of disease incidence on the microbiome was depended on sampling time after
      weaning (P = 0.0462) for 2015, while the main effects of sampling time after
      weaning (P = 0.00992) and disease phenotype (P = 0.012) were significant for
      2016. These data for 2016 demonstrate that in addition to bacterial profiles
      changing throughout weaning, calves diagnosed with BRDC have different bacterial
      profiles compared to their control cohorts. In addition, evaluation of the
      microbiome identified predominant bacteria genera in the upper nasal cavity
      included those previously reported to be associated with cattle diagnosed with
      BRDC including Mycoplasma sp., Psychrobacter sp., and Mannheimia sp. In summary,
      these results demonstrate that shorter, less invasive 6-inch nasal swabs produce
      similar results to deep nasopharyngeal swabs.

PMID- 29659873
TI  - Two new Salmonella genomic islands 1 from Proteus mirabilis and description of
      blaCTX-M-15 on a variant (SGI1-K7).
AB  - Objectives: To characterize the structure of Salmonella genomic islands 1 (SGI1s)
      from two clinical Proteus mirabilis isolates: one producing an ESBL and the other
      a penicillinase. Methods: WGS completed by PCR and Sanger sequencing was
      performed to determine sequences of SGI1s from Pm2CHAMA and Pm37THOMI strains.
      Results: Two new variants of SGI1 named SGI1-Pm2CHAMA (53.6 kb) and SGI1-K7 (55.1
      kb) were identified. The backbone of SGI1-Pm2CHAMA shared 99.9% identity with
      that of SGI1. Its MDR region (26.3 kb) harboured two class 1 integrons (an In2
      type integron and an In4-type integron) containing in particular a qacH cassette
      (encoding a quaternary ammonium compound efflux pump). These two integrons framed
      a complex region (harbouring among others blaCARB-4) resulting from transposon
      insertions mediated by IS26 and successive transposition events of ISs (ISAba14
      isoform and the new ISPmi2). The second variant (SGI1-K7) had the same backbone
      as SGI1-K. Its MDR region (29.7 kb) was derived from that of SGI1-K and was
      generated by three events. The two main events were mediated by IS26: inversion
      of a large portion of the MDR region of SGI1-K and insertion of a structure
      previously reported on plasmids carried by prevalent and successful MDR clones of
      Enterobacteriaceae. This last event led to the insertion of the blaCTX-M-15 gene
      into SGI1-K7. Conclusions: This study confirmed the great plasticity of the MDR
      region of SGI1 and its potential key role for the dissemination of clinically
      significant antibiotic resistance among Enterobacteriaceae.

PMID- 29659874
TI  - Carfentanil in Impaired Driving Cases and the Importance of Drug Seizure Data.
AB  - Drug seizures containing carfentanil continue to increase in Palm Beach County,
      FL, USA despite international efforts to control the distribution of the drug.
      The analysis of drug seizures from the county in 2016 and 2017 demonstrated that
      carfentanil was the most commonly identified fentanyl analog and was most often
      detected in combination with heroin, fentanyl, furanyl fentanyl and/or other
      fentanyl analogs. Carfentanil is an ultra-potent opioid requiring a method with
      adequate sensitivity for detection in blood specimens from impairment cases.
      Previous research indicated that carfentanil could not be identified in
      biological specimens by routine drug testing protocols and that detection
      requires targeted analysis with greater sensitivity. Due to the prevalence of
      carfentanil in drug seizures, a sensitive targeted qualitative method by liquid
      chromatography tandem mass spectrometry in antemortem blood samples was
      evaluated, validated and implemented. The method included identification of
      carfentanil, acetyl fentanyl, beta-hydroxythiofentanyl, butyryl fentanyl,
      fentanyl, furanyl fentanyl, kavain, mitragynine, MT-45 and U-47700. In 2017
      carfentanil was the second most frequently detected drug, after ethanol, in
      driving under the influence blood cases. Of all blood cases in which drug testing
      was performed (n = 145), carfentanil was detected in 38% followed by alprazolam
      (29%), fentanyl (27%), delta-9-tetrahydrocannabinol (24%) and morphine (23%). In
      toxicology cases carfentanil was rarely identified alone (only four cases) and
      was most commonly identified with other opioids (73% of cases), benzodiazepines
      (43%) and stimulants (29%). The high incidence of carfentanil-positive cases
      detected by this method underscores the importance of continually monitoring
      regional drug seizure trends, and evaluating the adequacy of toxicology testing
      panels based on these trends.

PMID- 29659875
TI  - Sensitive and simultaneous determination of nine anticoagulant rodenticides in
      human blood by UPLC-MS-MS with phospholipid removal pretreatment.
AB  - A sensitive and rapid method for the simultaneous determination of nine
      anticoagulant rodenticides (ARs) in human blood is reported herein. The method
      involves phospholipid removal pretreatment for reduced matrix effect (ME) and
      detection with ultra-performance liquid chromatography coupled with tandem mass
      spectrometry. Satisfactory recoveries were achieved ranging from 80.6% to 113.1%
      for the nine analytes, with the intra-day relative standard deviations (RSDs) in
      the range of 3.4-7.9% and inter-day RSDs in the range of 4.1-8.3%, indicating
      good precision. Linear relationships with correlation coefficients above 0.998 (n
      = 6) were found in the range of 1-2,000 ng/mL. High sensitivity was achieved with
      limits of detection ranging from 0.02 to 0.3. The application of phospholipid
      removal step significantly optimized the ME, and the reduction of ME ranged from
      6.1% to 15.5%. This method was successfully applied to the determination of ARs
      for blood samples from real forensic cases. These results prove that this method
      is reliable for rapid forensic and clinical diagnosis. The removal capabilities
      for five representative phospholipids that are abundant in blood were evaluated
      individually with PhreeTM phospholipid removal plates. While significant
      capabilities for phospholipid removal were confirmed, the results showed that the
      removal capability for certain phospholipid could be improved.

PMID- 29659876
TI  - Effects of Lactobacillus reuteri LR1 on the growth performance, intestinal
      morphology, and intestinal barrier function in weaned pigs.
AB  - The objective of this study was to investigate the effects of Lactobacillus
      reuteri LR1, a new strain isolated from the feces of weaned pigs, on the growth
      performance, intestinal morphology, immune responses, and intestinal barrier
      function in weaned pigs. A total of 144 weaned pigs (Duroc * Landrace *
      Yorkshire, 21 d of age) with an initial BW of 6.49 +/- 0.02 kg were randomly
      assigned to 3 dietary treatments with 8 replicate pens, each of per treatment and
      6 pigs. Pigs were fed a basal diet (CON, controls), the basal diet supplemented
      with 100 mg/kg olaquindox and 75 mg/kg aureomycin (OA) or the basal diet
      supplemented with 5 * 1010 cfu/kg L. reuteri LR1 for a 14-d period. At the end of
      study, the ADG, ADFI, and G:F were calculated, and 1 randomly selected pig from
      each pen was euthanized for sample collection. The LR1 increased ADG (22.73%, P <
      0.05) compared with CON. The villus height of the ileum was increased (P < 0.05)
      and crypt depth in duodenum was reduced (P < 0.05), along with increased (P <
      0.05) villus height to crypt depth ratio of the jejunum and ileum by LR1 compared
      with CON and OA. LR1 increased (P < 0.05) ileal mucosal content of IL-22 and
      transforming growth factor-beta compared with OA. Compared with CON, LR1
      increased (P < 0.05) and OA decreased (P < 0.05) the ileal content of secretory
      immunoglobulin A (sIgA), and the abundance of transcripts of porcine beta
      defensin 2 and protegrin 1-5. Compared with CON, LR1 increased (P < 0.05) tight
      junction protein zonula occludens-1 and occludin transcripts in the mucosa of the
      jejunum and ileum, and those of mucin-2 in ileal mucosa. The relative expression
      of toll-like receptor 2 (TLR2) and TLR4 were increased (P < 0.05) in ileal mucosa
      in pigs fed LR1 compared with CON. In conclusion, these data indicated that
      dietary LR1 supplementation at 5 * 1010 cfu/kg improved growth performance,
      intestinal morphology, and intestinal barrier function in weaned pigs.

PMID- 29659877
TI  - Cytosolic phosphoenolpyruvate carboxykinase is a response gene involved in
      porcine adipocyte adaptation to heat stress.
AB  - Heat stress (HS) leads to increased lipid storage and expression of cytosolic
      phosphoenolpyruvate carboxykinase (PCK1) in pig adipocytes. However, the
      importance of PCK1 activation and lipid storage in the adaptive response to HS is
      unknown. Therefore, in vitro experiments were conducted to investigate the effect
      of PCK1 inhibition with 3-mercaptopicolinic acid (3MPA) on lipid storage and
      adipocyte response during HS. In vitro culture of adipocytes under HS (41.0 
      degrees C) increased (P < 0.05) triacylglycerol accumulation compared with
      control (37.0  degrees C). HS increased (P < 0.05) reactive oxygen species level
      and 3MPA further upregulated (P < 0.05) its level. Heat shock protein 70 (HSP70)
      gene expression was induced (P < 0.05) by HS compared to control, and PCK1
      inhibition with 3MPA attenuated (P < 0.05) its induction by HS. The endoplasmic
      reticulum (ER) stress markers, C/EBP homologous protein (CHOP) was also
      upregulated by HS and 3MPA further upregulated (P < 0.05) CHOP mRNA level. These
      results suggest that with inhibition of PCK1 during HS, in vitro cultured
      adipocytes were less able to induce adaptive responses such as upregulation of
      HSP70 and triglycerides, and this exacerbated ER stress during HS. Thus, PCK1 may
      function to alleviate ER stress that occurs during HS.

PMID- 29659878
TI  - Retail stability of three beef muscles from grass-, legume-, and feedlot-finished
      cattle.
AB  - This study aimed to determine the influence of finishing diet on beef appearance
      and lipid oxidation of three beef muscles. A total of 18 Angus steers were
      selected from three diet treatments: grass-finished (USUGrass), legume-finished
      (USUBFT), and grain-finished (USUGrain). After processing, longissimus thoracis
      (LT), triceps brachii (TB), and gluteus medius (GM) steaks were evaluated over a
      7-d display period. A muscle * diet interaction was observed for instrumental
      lightness (L*) and redness (a*) (P <= 0.001). Within each combination, USUGrass
      was considered darker with lower (P < 0.05) L* compared with USUGrain. For
      USUBFT, L* was similar to USUGrain for the TB and LT, while the L* of USUBFT and
      USUGrain GM differed (P < 0.05). In terms of redness, LT a* values were elevated
      (P < 0.05) in USUGrass compared with USUBFT and USUGrain. For GM steaks, a* of
      USUBFT and USUGrass were each greater (P < 0.05) than USUGrain. Surface a* of TB
      steaks were greatest (P < 0.05) for USUGrass followed by USUBFT, and with
      USUGrain, being lowest (P < 0.05). An overall increase in L* was observed
      throughout display dependent on diet (P = 0.013). During display, USUGrain steaks
      had the greatest (P < 0.05) L* followed by USUBFT and USUGrass. Additionally, a
      day * muscle interaction was observed for a* (P = 0.009). Initially, TB steaks
      had the greatest (P < 0.05) a* values. However, at day 3, a* values were similar
      (P > 0.05) among muscles. Visual color scores were in agreement with loss of
      redness (a*) during display, dependent on diet and muscle type (P < 0.001).
      Similarly, a day * diet * muscle interaction was observed for visual
      discoloration (P < 0.001). Day and diet interacted to influence thiobarbituric
      acid reactive substances (TBARS) (P < 0.001). Initial values did not differ (P >
      0.05) between USUGrain and USUBFT; however, USUGrass had lower initial (P < 0.05)
      TBARS than both USUGrain and USUBFT. At days 3 and 7, TBARS were greatest (P <
      0.05) in USUGrain steaks, followed by USUBFT, which was greater (P < 0.05) than
      USUGrass. A diet * muscle interaction was observed for 10 volatile compounds
      originating from lipid degradation (P <= 0.013). These compounds were less (P <
      0.05) abundant in USUGrass compared to TB or GM of USUGrain. This study
      determined grass-finished beef to have a darker more red color and less lipid
      oxidation in multiple muscles. Possible mechanisms for this may include an
      increase in endogenous antioxidants in grass-finished beef.

PMID- 29659879
TI  - Orlistat Therapy for Children With Type 1 Hyperlipoproteinemia: A Randomized
      Clinical Trial.
AB  - Context: Patients with type 1 hyperlipoproteinemia (T1HLP), a rare genetic
      disorder, have extreme chylomicronemia and recurrent episodes of acute
      pancreatitis. Currently, the only therapeutic option is to consume an extremely
      low-fat diet because the triglyceride-lowering medications are not efficacious.
      Objective: To determine the efficacy of orlistat, a gastric and pancreatic lipase
      inhibitor, in reducing serum triglyceride levels in patients with T1HLP. Design
      and Setting: We conducted a randomized, open-label, clinical trial with a four
      period, two-sequence ("orlistat" and "off orlistat" for 3 months), crossover
      study design. Patients: Two unrelated young Asian Indian males (11 and 9 years
      old) with T1HLP due to homozygous large GPIHBP1 deletions were enrolled at the UT
      Southwestern Medical Center. The patients were randomized to receive 3 months of
      orlistat or no therapy (off), then crossed over to the other arm, and this
      sequence was then repeated. Fasting serum triglyceride levels, fat-soluble
      vitamins, and gastrointestinal side effects were assessed. Results: Compared with
      the two off periods, orlistat therapy reduced serum triglycerides by 53.3% and
      53.0% in patient 1 and 45.8% and 62.2% in patient 2. There was no deficiency of
      fat-soluble vitamin levels, and their growth continued. There were no serious
      adverse effects of orlistat; patient 1 had a mild increase in passage of gas and
      bloating, and patient 2 had constipation with mild stool leakage. Conclusion:
      Orlistat is safe and highly efficacious in lowering serum triglycerides in
      children with T1HLP and should be the first-line therapy in conjunction with an
      extremely low-fat diet.

PMID- 29659880
TI  - Eight Years of Clinical Legionella PCR Testing Illustrates a Seasonal Pattern.

PMID- 29659881
TI  - Results from the Survey of Antibiotic Resistance (SOAR) 2014-16 in Russia.
AB  - Objectives: To determine antibiotic susceptibility in isolates of Streptococcus
      pneumoniae and Haemophilus influenzae collected in 2014-16 from Russia. Methods:
      MICs were determined by CLSI broth microdilution and susceptibility was assessed
      using CLSI, EUCAST and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints.
      Results: A total of 279 S. pneumoniae and 279 H. influenzae were collected.
      Overall, 67.0% of S. pneumoniae were penicillin susceptible by CLSI oral/EUCAST
      and 93.2% by CLSI intravenous (iv) breakpoints. All were fluoroquinolone
      susceptible, with amoxicillin, amoxicillin/clavulanic acid and ceftriaxone
      susceptibility >=92.8% by CLSI and PK/PD breakpoints. Isolates showed lower
      susceptibility to cefuroxime, cefaclor, macrolides and
      trimethoprim/sulfamethoxazole by CLSI criteria: 85.0%, 76.7%, 68.8% and 67.7%,
      respectively. Generally, susceptibility was slightly lower by EUCAST criteria,
      except for cefaclor, for which the difference in susceptibility was much greater.
      Penicillin-resistant isolates had low susceptibility (<=60%) to all agents except
      fluoroquinolones. All 279 H. influenzae were ceftriaxone susceptible, 15.4% were
      beta-lactamase positive and >=97.5% were amoxicillin/clavulanic acid susceptible
      (CLSI, EUCAST and PK/PD breakpoints). Four isolates were fluoroquinolone non
      susceptible by current EUCAST criteria. A major discrepancy was found with
      azithromycin susceptibility between CLSI (99.3%) and EUCAST and PK/PD (2.2%)
      breakpoints. Trimethoprim/sulfamethoxazole was poorly active (62.7% susceptible).
      Conclusions: Susceptibility to penicillin (oral), macrolides and
      trimethoprim/sulfamethoxazole was low in S. pneumoniae from Russia. However,
      isolates were fully susceptible to fluoroquinolones and >=92.8% were susceptible
      to amoxicillin, amoxicillin/clavulanic acid and ceftriaxone. Isolates of H.
      influenzae only showed reduced susceptibility to ampicillin, cefaclor,
      clarithromycin and trimethoprim/sulfamethoxazole. Some differences were detected
      between CLSI, EUCAST and PK/PD breakpoints, especially with cefaclor, cefuroxime
      and macrolides. These data suggest further efforts are required to harmonize
      international breakpoints.

PMID- 29659882
TI  - Results from the Survey of Antibiotic Resistance (SOAR) 2014-16 in Bulgaria,
      Romania, Serbia and Croatia.
AB  - Objectives: To determine antibiotic susceptibility of isolates of Streptococcus
      pneumoniae (n = 573) and Haemophilus influenzae (n = 345) collected in 2014-16
      from Bulgaria, Romania, Serbia and Croatia. Methods: MICs were determined by CLSI
      broth microdilution and susceptibility was assessed using CLSI, EUCAST and
      pharmacokinetic/pharmacodynamic (PK/PD) breakpoints. Results: Among S.
      pneumoniae, susceptibility was generally lowest in Romania and Serbia and highest
      in Bulgaria. Rates of susceptibility to penicillin (CLSI oral or EUCAST) were
      22.3% and 21.8% in Romania and Serbia respectively, 57% in Croatia and 86.6% in
      Bulgaria. Similarly, macrolide susceptibility using CLSI/EUCAST breakpoints was
      low in Romania and Serbia (~28% and 34.5%, respectively), higher in Croatia
      (55.9%) and highest in Bulgaria (~75%). Only fluoroquinolones were active against
      all isolates in all four countries. Susceptibility was higher and variability
      across countries less pronounced for H. influenzae. Susceptibility by CLSI
      criteria to amoxicillin/clavulanic acid, azithromycin, cefuroxime, ceftriaxone
      and fluoroquinolones was >=98% in all countries. Ampicillin susceptibility ranged
      from 85.3% in Romania to 100% in Bulgaria. Much greater variability was seen
      across breakpoints. Susceptibility to azithromycin and cefuroxime using CLSI
      criteria was >=98% in all four countries, but was 0%-1% by EUCAST criteria.
      Conclusions: The variability in antimicrobial susceptibility using different
      breakpoints makes it difficult for clinicians to interpret antimicrobial
      resistance data, and efforts should be made to harmonize breakpoints. The
      variability found across the four neighbouring countries demonstrates the need to
      monitor and publish national and local resistance patterns. These findings
      provide information critical for the selection of appropriate antimicrobial
      agents for the treatment of S. pneumoniae and H. influenzae.

PMID- 29659883
TI  - Results from the Survey of Antibiotic Resistance (SOAR) 2014-16 in the Czech
      Republic.
AB  - Objectives: To determine the antibiotic susceptibility of isolates of
      Streptococcus pneumoniae and Haemophilus influenzae collected in 2014-16 from
      patients with community-acquired respiratory infections in the Czech Republic.
      Methods: MICs were determined by CLSI broth microdilution and susceptibility was
      assessed using CLSI, EUCAST and pharmacokinetic/pharmacodynamic (PK/PD)
      breakpoints. Results: S. pneumoniae isolates (n = 200) showed high rates of
      susceptibility (>95%) to amoxicillin, amoxicillin/clavulanic acid, penicillin
      [intravenous (iv) non-meningitis], ceftriaxone, cefuroxime and the
      fluoroquinolones using CLSI breakpoints. Susceptibility to cefaclor and
      trimethoprim/sulfamethoxazole was 94%-94.5%, to penicillin (oral) 91.5% and to
      the macrolides 89.5%. Susceptibility of H. influenzae (n = 197) to
      amoxicillin/clavulanic acid, ceftriaxone, cefuroxime, azithromycin and the
      fluoroquinolones was >=98% by CLSI criteria. Rates of susceptibility to the
      remaining agents were >=75% except for clarithromycin at 37.1%. Great variability
      was seen across breakpoints, especially for the macrolides, cefaclor and
      cefuroxime (oral), 98.0% of H. influenzae showing susceptibility to the latter by
      CLSI criteria, 69.5% by PK/PD and 1.5% by EUCAST standards. The beta-lactamase
      rate was 13.7% with no beta-lactamase-negative-ampicillin-resistant (BLNAR)
      isolates by CLSI criteria. Conclusions: Antibiotic resistance among the two major
      respiratory pathogens remained low in the Czech Republic. These findings support
      local clinicians in continuing the historically restrictive use of antibiotics in
      the Czech Republic, with selection of narrower-spectrum agents for the empirical
      therapy of community-acquired respiratory tract infections. This highlights one
      of the great benefits of continuous surveillance of antimicrobial resistance:
      knowledge of current local resistance patterns reduces the need to choose broad
      spectrum agents that contribute to increasing resistance worldwide.

PMID- 29659884
TI  - Results from the Survey of Antibiotic Resistance (SOAR) 2014-16 in Greece.
AB  - Objectives: To determine antimicrobial susceptibility in isolates of
      Streptococcus pneumoniae and Haemophilus influenzae collected in 2014-16 from
      patients with community-acquired respiratory tract infections in Greece. Methods:
      MICs were determined by CLSI broth microdilution and susceptibility assessed
      using CLSI, EUCAST and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints.
      Results: A total of 99 S. pneumoniae and 52 H. influenzae isolates were
      collected. Overall, 36.4% of S. pneumoniae were penicillin susceptible by CLSI
      oral/EUCAST and 88.9% by CLSI intravenous (iv) breakpoints. All were
      fluoroquinolone susceptible with >=94% of isolates also susceptible to
      amoxicillin, amoxicillin/clavulanic acid and ceftriaxone by CLSI and PK/PD
      breakpoints. Trimethoprim/sulfamethoxazole, cefuroxime, cefaclor and macrolides
      were less active, with rates of susceptibility of 83.8%, 69.7%, 50.5% and 49.5%,
      respectively, by CLSI. Generally susceptibility was the same or slightly lower by
      EUCAST, but the cefaclor difference was much greater. Among H. influenzae, 15.4%
      of isolates were beta-lactamase positive. Susceptibility to
      amoxicillin/clavulanic acid, ceftriaxone, cefuroxime and the fluoroquinolones was
      seen in >95% of isolates by CLSI criteria. Susceptibility to azithromycin was
      seen in 94.2% of isolates using CLSI breakpoints, but clarithromycin
      susceptibility was lower (61.5%). However, susceptibility to both macrolides was
      seen in <5% of isolates by PK/PD and EUCAST criteria. Susceptibility to
      trimethoprim/sulfamethoxazole was seen in 71.2% of isolates. Conclusions: Owing
      to the high prevalence of macrolide resistance among S. pneumoniae and the
      reduced activity of clarithromycin against H. influenzae, it appears that these
      agents are not appropriate as monotherapy for community-acquired pneumonia in
      Greece. Amoxicillin/clavulanic acid, on the other hand, maintained excellent in
      vitro activity and, as opposed to the similarly effective fluoroquinolones, is
      safe to use in paediatric patients.

PMID- 29659885
TI  - Results from the Survey of Antibiotic Resistance (SOAR) 2014-16 in Ukraine and
      the Slovak Republic.
AB  - Objectives: To determine antibiotic susceptibility in isolates of Streptococcus
      pneumoniae and Haemophilus influenzae collected in 2014-16 from Ukraine and the
      Slovak Republic. Methods: MICs were determined by CLSI broth microdilution and
      susceptibility was assessed using CLSI, EUCAST and
      pharmacokinetic/pharmacodynamic (PK/PD) breakpoints. Results: S. pneumoniae
      isolates collected in Ukraine (n = 100) showed susceptibility rates >=97% for
      amoxicillin, amoxicillin/clavulanic acid, penicillin [intravenous (iv) non
      meningitis] and fluoroquinolones, between 83% and 86% for oral penicillin,
      macrolides and cefaclor, and 75% for trimethoprim/sulfamethoxazole.
      Susceptibility was substantially lower in the Slovak Republic (n = 95). All
      isolates were susceptible to the fluoroquinolones, but susceptibility to
      penicillin, amoxicillin, amoxicillin/clavulanic acid, cefuroxime and
      trimethoprim/sulfamethoxazole varied between 61% and 64%, with only 44% of
      isolates susceptible to the macrolides. Susceptibility of H. influenzae was more
      homogeneous, with susceptibility to amoxicillin/clavulanic acid, ceftriaxone,
      cefuroxime, azithromycin and the fluoroquinolones seen in >90% of isolates by
      CLSI criteria in both countries. Much greater variability was seen across
      breakpoints, especially for azithromycin, cefaclor and cefuroxime. The beta
      lactamase rate was 5.1% (5/98) in the Slovak Republic and 7.3% (7/96) in Ukraine,
      but the Slovak Republic also had a relatively high rate of beta-lactamase
      negative-ampicillin-resistant (BLNAR) isolates (7.1%; 7/98). Conclusions: The
      variability found across these two neighbouring countries illustrates the need to
      monitor and publish national and local resistance patterns. This information is
      not only critical for effective empirical therapy but can also be used to help
      shape and support antimicrobial stewardship efforts in order to limit antibiotic
      resistance.

PMID- 29659886
TI  - Bone Parameters in Anorexia Nervosa and Athletic Amenorrhea: Comparison of Two
      Hypothalamic Amenorrhea States.
AB  - Objective: We have reported low bone mineral density (BMD), impaired bone
      structure, and increased fracture risk in participants with anorexia nervosa (AN)
      and normal-weight oligoamenorrheic athletes (OAs). However, data directly
      comparing compartment-specific bone parameters in participants with AN, OAs, and
      controls are lacking. Design: A total of 468 female participants 14 to 21.9 years
      old were included: 269 with AN, 104 OAs, and 95 normal-weight eumenorrheic
      controls. Dual-energy x-ray absorptiometry was used to assess areal BMD (aBMD) of
      the whole body less head (WBLH), spine, and hip. High-resolution peripheral
      quantitative computed tomography was used to assess volumetric BMD (vBMD), bone
      geometry, and structure at the non-weight-bearing distal radius and weight
      bearing distal tibia. Results: Participants with AN had lower WBLH and hip aBMD z
      scores than OAs and controls (P < 0.0001). Participants with AN and OAs had lower
      spine aBMD z scores than controls (P < 0.01). At the radius, total and cortical
      vBMD, percentage cortical area, and thickness were lower in the AN and OA groups
      than in controls (P <= 0.04); trabecular vBMD was lower in participants with AN
      than controls. At the tibia, participants with AN had lower measures for most
      parameters compared with OAs and controls (P < 0.05); OAs had lower cortical vBMD
      than controls (P = 0.002). Participants with AN and OAs had higher fracture rates
      than controls. Stress fracture prevalence was highest in OAs (P < 0.0001);
      nonstress fracture prevalence was highest in participants with AN (P < 0.05).
      Conclusion: AN is deleterious to bone at all sites and both bone compartments. A
      high stress fracture rate in OAs, who have comparable WBLH and hip aBMD measures
      to controls, indicates that BMD in these women may need to be even higher to
      avoid fractures.

PMID- 29659887
TI  - Homeostasis Model Assessment of Insulin Resistance and Survival in Patients With
      Diabetes and Acute Coronary Syndrome.
AB  - Objective: Insulin resistance has been linked to development and progression of
      atherosclerosis and is present in most patients with type 2 diabetes. Whether the
      degree of insulin resistance predicts adverse outcomes in patients with type 2
      diabetes and acute coronary syndrome (ACS) is uncertain. Design: The Effect of
      Aleglitazar on Cardiovascular Outcomes after Acute Coronary Syndrome in Patients
      with Type 2 Diabetes Mellitus trial compared the peroxisome proliferator
      activated receptor-alpha/gamma agonist aleglitazar with placebo in patients with
      type 2 diabetes and recent ACS. In participants not treated with insulin, we
      determined whether baseline homeostasis model assessment of insulin resistance
      (HOMA-IR; n = 4303) or the change in HOMA-IR on assigned study treatment (n =
      3568) was related to the risk of death or major adverse cardiovascular events
      (cardiovascular death, myocardial infarction, and stroke) in unadjusted and
      adjusted models. Because an inverse association of HOMA-IR with N-terminal pro-B
      type natriuretic peptide (NT-proBNP) has been described, we specifically examined
      effects of adjustment for the latter. Results: In unadjusted analysis, twofold
      higher baseline HOMA-IR was associated with lower risk of death [hazard ratio
      (HR): 0.79, 95% CI: 0.68 to 0.91, P = 0.002]. Adjustment for 24 standard
      demographic and clinical variables had minimal effect on this association.
      However, after further adjustment for NT-proBNP, the association of HOMA-IR with
      death was no longer present (adjusted HR: 0.99, 95% CI: 0.83 to 1.19, P = 0.94).
      Baseline HOMA-IR was not associated with major adverse cardiovascular events, nor
      was the change in HOMA-IR on study treatment associated with death or major
      adverse cardiovascular events. Conclusions: After accounting for levels of NT
      proBNP, insulin resistance assessed by HOMA-IR is not related to the risk of
      death or major adverse cardiovascular events in patients with type 2 diabetes and
      ACS.

PMID- 29659888
TI  - Randomized, Placebo-Controlled Trial to Evaluate Effects of Eplerenone on
      Metabolic and Inflammatory Indices in HIV.
AB  - Context: HIV-infected individuals demonstrate increased renin-angiotensin
      aldosterone system activation in association with visceral adiposity, insulin
      resistance, and inflammation. A physiologically based treatment approach
      targeting mineralocorticoid receptor (MR) blockade may improve metabolic and
      inflammatory indices in HIV. Objective: To investigate effects of eplerenone on
      insulin sensitivity, inflammatory indices, and other metabolic parameters in HIV.
      Design: Six-month, double-blind, randomized, placebo-controlled trial. Setting:
      Academic clinical research center. Participants: HIV-infected individuals with
      increased waist circumference and abnormal glucose homeostasis. Intervention:
      Eplerenone 50 mg or placebo daily. Outcome: The primary end point was change in
      insulin sensitivity measured by the euglycemic-hyperinsulinemic clamp technique.
      Secondary end points included change in body composition and inflammatory
      markers. Results: Forty-six individuals were randomized to eplerenone (n = 25) vs
      placebo (n = 21). Eplerenone did not improve insulin sensitivity [0.48 (-1.28 to
      1.48) vs 0.43 (-1.95 to 2.55) mg/min/MUIU/mL insulin; P = 0.71, eplerenone vs
      placebo] when measured by the gold standard euglycemic-hyperinsulinemic clamp
      technique. Intramyocellular lipids (P = 0.04), monocyte chemoattractant protein-1
      (P = 0.04), and high-density lipoprotein (P = 0.04) improved among those
      randomized to eplerenone vs placebo. Trends toward decreases in interleukin-6 (P
      = 0.10) and high-sensitivity C-reactive protein (P = 0.10) were also seen with
      eplerenone vs placebo. Plasma renin activity and aldosterone levels increased in
      the eplerenone vs placebo-treated group, demonstrating expected physiology. MR
      antagonism with eplerenone was well tolerated among the HIV population, with no
      considerable changes in blood pressure or potassium. Conclusion: MR blockade may
      improve selected metabolic and inflammatory indices in HIV-infected individuals.
      Further studies are necessary to understand the clinical potential of MR
      antagonism in HIV.

PMID- 29659889
TI  - Anti-Ebola Virus Antibody Levels in Convalescent Plasma and Viral Load After
      Plasma Infusion in Patients With Ebola Virus Disease.
AB  - Background: Ebola virus (EBOV) neutralizing antibody in plasma may reduce viral
      load following administration of plasma to patients with Ebola virus disease
      (EVD), but measurement of these antibodies is complex. Methods: Anti-EBOV
      antibody was measured by 2 neutralization and 2 enzyme-linked immunosorbent
      assays (ELISAs) in convalescent plasma (ECP) from 100 EVD survivor donors in
      Liberia. Viral load was assessed repetitively in patients with EVD participating
      in a clinical trial of enhanced standard of care plus ECP. Results: All 4 anti
      EBOV assays were highly concordant for detection of EBOV antibody. Antibodies
      were not detected in plasma specimens obtained from 15 of 100 donors, including 7
      with documented EBOV-positive reverse-transcription polymerase chain reaction
      during EVD. Viral load was reduced following each dose in the 2 clinical trial
      participants who received ECP with higher antibody levels but not in the 2 who
      received ECP with lower antibody levels. Conclusions: Recovery from EVD can occur
      with absence of detectable anti-EBOV antibody several months after disease onset.
      ELISAs may be useful to select ECP donors or identify ECP units that contain
      neutralizing antibody. ECP with higher anti-EBOV antibody levels may have greater
      effect on EBOV load-an observation that requires further investigation. Clinical
      Trials Registration: NCT02333578.

PMID- 29659890
TI  - Postharvest Irradiation Treatment for Quarantine Control of Western Flower Thrips
      (Thysanoptera: Thripidae).
AB  - The western flower thrips, Frankliniella occidentalis (Pergande) (Thysanoptera:
      Thripidae), is an important pest of fresh horticultural produce and as such is
      considered a biosecurity risk in many countries from which it is absent.
      Information is needed on the radiation tolerance of important surface pests of
      quarantine importance such as F. occidentalis so that phytosanitary irradiation
      treatments for exported fresh commodities can be lowered to below the 400 Gy
      generic treatment currently approved for most insects in the United States and
      Australia. Lowering the dose will help minimize any product quality problems,
      reduce costs, and shorten treatment time. In large-scale confirmatory trials
      conducted in two independent laboratories in Hawaii and Australia, a dose of 250
      Gy (measured doses 222-279 Gy) applied to adult F. occidentalis on green beans
      resulted in no reproduction in 5,050 treated individuals. At 250 Gy, the
      effective dose is significantly below the 400 Gy generic dose, demonstrating that
      irradiation at this lowered level is an effective method for the disinfestation
      of F. occidentalis from fresh horticultural produce.

PMID- 29659891
TI  - Sampling Transgenic Corn Producing Bt Toxins for Corn Earworm Injury.
AB  - Transgenic corn, Zea mays L., hybrids expressing insecticidal proteins from
      Bacillus thuringiensis (Bt) and non-Bt near isolines were sampled for injury from
      Helicoverpa zea (Boddie) in North and South Carolina from 2012 to 2017. A total
      of 7,260 ears were sampled, with an average kernel injury from H. zea feeding of
      1.22 +/- 0.02 (SEM) cm2. The chi2 statistics for observed and Poisson predicted
      distributions of the area of kernel injury indicated nonrandom distributions for
      all hybrids (P < 0.0001), which were confirmed by all variance to mean ratios
      (ID) being significantly greater than one. Slopes b of Taylor's power law and
      beta of Iwao's patchiness regressions for the area of kernel injury were all
      either not significantly (P > 0.05) different from a value of one or
      significantly (P < 0.05) less than a value of one. Within each family of hybrids,
      relationships between proportions of ear samples with injury and area of kernel
      injury were similar among Bt and non-Bt hybrids. For the same level of injury, to
      reach a population estimate within 10% of the mean (Dx = 0.1), the number of
      sample units required was large (>100), particularly at low levels of injury.
      Sample sizes for estimates within 30% of the mean (Dx = 0.3) were considerable
      smaller. Sample size for Bt hybrids relative to non-Bt hybrids varied with the
      levels of injury and with family. Our study has provided the first sampling
      recommendations for population estimates of H. zea injury to corn ears.

PMID- 29659892
TI  - Effect of Physiological State on Female Melon Fly (Diptera: Tephritidae)
      Attraction to Host and Food Odor in the Field.
AB  - Foraging behavior of wild female melon fly, Bactrocera (Zeugodacus) cucurbitae
      Coquillett, a worldwide pest of economically important cucurbit crops, was
      examined through mark and recapture studies in both wild (Kona: dominated by the
      invasive weed ivy gourd, Coccinea grandis [L.] Voigt [Cucurbitaceae]), and
      cultivated (Kapoho: dominated by papaya, Carica papaya L. [Caricaceae] orchards)
      habitats on Hawaii Island. In particular, the extent to which wild melon flies
      and color-marked F2 females responded to cucumber odor and Solulys yeast
      hydrolysate laced with ammonium acetate (1%, wt/vol) according to sexual maturity
      stage and degree of protein hunger was documented. Kona results indicated that
      more wild and color-marked F2 females responded to cucumber (Cucumis sativus L.
      [Cucurbitaceae]) odor than to protein odor with the exception of captured wild
      flies without eggs, which responded similarly to protein bait and cucumber odor.
      Results with captured wild females and color-marked F2 females in Kapoho
      suggested a significant preference for cucumber odor over protein odor regardless
      of whether or not they had eggs in their ovaries with the exception of protein
      deprived color-marked F2 females, which responded to both odors in equal numbers.
      Implications of these new findings based on wild melon flies in natural habitats
      are discussed with respect to integrated pest management control strategies with
      protein bait sprays used in Hawaii. The possibility of adding cucurbit volatiles
      to protein-based baits is discussed.

PMID- 29659893
TI  - Temporal Mitogenomics of the Galapagos Giant Tortoise from Pinzon Reveals
      Potential Biases in Population Genetic Inference.
AB  - Empirical population genetic studies generally rely on sampling subsets of the
      population(s) of interest and of the nuclear or organellar genome targeted,
      assuming each is representative of the whole. Violations of these assumptions may
      impact population-level parameter estimation and lead to spurious inferences.
      Here, we used targeted capture to sequence the full mitochondrial genome from 123
      individuals of the Galapagos giant tortoise endemic to Pinzon Island (Chelonoidis
      duncanensis) sampled at 2 time points pre- and postbottleneck (circa 1906 and
      2014) to explicitly assess differences in diversity estimates and demographic
      reconstructions based on subsets of the mitochondrial genome versus the full
      sequences and to evaluate potential biases associated with diversity estimates
      and demographic reconstructions from postbottlenecked samples alone. Haplotypic
      diversities were equal between the temporal samples based on the full
      mitochondrial genome, but single gene estimates suggested either decreases or
      increases in diversity depending upon the region. Demographic reconstructions
      based on the full sequence were more similar between the temporal samples than
      those based on the control region alone, or a subset of 3 regions, where the
      trends in population size changes shifted in magnitude and direction between the
      temporal samples. In all cases, the estimated coalescent point was more distant
      for the historical than contemporary sample. In summary, our results empirically
      demonstrate the influence of sampling bias when interpreting population genetic
      patterns and punctuate the need for careful consideration of potentially
      conflicting evolutionary signal across the mitochondrial genome.

PMID- 29659894
TI  - Usability of American Sign Language Videos for Presenting Mathematics Assessment
      Content.
AB  - There is considerable interest in determining whether high-quality American Sign
      Language videos can be used as an accommodation in tests of mathematics at both K
      12 and postsecondary levels; and in learning more about the usability (e.g.,
      comprehensibility) of ASL videos with two different types of signers - avatar
      (animated figure) and human. The researchers describe the results of
      administering each of nine pre-college mathematics items in both avatar and human
      versions to each of 31 Deaf participants with high school and post-high school
      backgrounds. This study differed from earlier studies by obliging the
      participants to rely on the ASL videos to answer the items. While participants
      preferred the human version over the avatar version (apparently due largely to
      the better expressiveness and fluency of the human), there was no discernible
      relationship between mathematics performance and signed version.

PMID- 29659895
TI  - Identification of Differential Transcriptional Patterns in Primary and Secondary
      Hyperparathyroidism.
AB  - Context: Hyperparathyroidism is associated with hypercalcemia and the excess of
      parathyroid hormone secretion; however, the alterations in molecular pattern of
      functional genes during parathyroid tumorigenesis have not been unraveled. We
      aimed at establishing transcriptional patterns of normal and pathological
      parathyroid glands (PGs) in sporadic primary (HPT1) and secondary
      hyperparathyroidism (HPT2). Objective: To evaluate dynamic alterations in
      molecular patterns as a function of the type of PG pathology, a comparative
      transcript analysis was conducted in subgroups of healthy samples, sporadic HPT1
      adenoma and hyperplasia, and HPT2. Design: Normal, adenomatous, HPT1, and HPT2
      hyperplastic PG formalin-fixed paraffin-embedded samples were subjected to
      NanoString analysis. In silico microRNA (miRNA) analyses and messenger RNA-miRNA
      network in PG pathologies were conducted. Individual messenger RNA and miRNA
      levels were assessed in snap-frozen PG samples. Results: The expression levels of
      c-MET, MYC, TIMP1, and clock genes NFIL3 and PER1 were significantly altered in
      HPT1 adenoma compared with normal PG tissue when assessed by NanoString and
      quantitative reverse transcription polymerase chain reaction. RET was affected in
      HPT1 hyperplasia, whereas CaSR and VDR transcripts were downregulated in HPT2
      hyperplastic PG tissue. CDH1, c-MET, MYC, and CaSR were altered in adenoma
      compared with hyperplasia. Correlation analyses suggest that c-MET, MYC, and
      NFIL3 exhibit collective expression level changes associated with HPT1 adenoma
      development. miRNAs, predicted in silico to target these genes, did not exhibit a
      clear tendency upon experimental validation. Conclusions: The presented gene
      expression analysis provides a differential molecular characterization of PG
      adenoma and hyperplasia pathologies, advancing our understanding of their
      etiology.

PMID- 29659896
TI  - Does Metformin Treatment During Pregnancy Modify the Future Metabolic Profile in
      Women With PCOS?
AB  - Context: Worldwide, metformin is prescribed to improve pregnancy outcome in
      polycystic ovary syndrome (PCOS). Metformin may also benefit future health by
      modulating increased metabolic stress during pregnancy. Objective: To investigate
      whether metformin during pregnancy modified future metabolic health in women with
      PCOS. Design: Follow-up study of a randomized controlled trial that compared
      metformin with placebo in women with PCOS. Mean follow-up period was 7.7 years
      (range, 5 to 11 years). Setting: Three university hospitals, seven local
      hospitals, and one gynecological specialist practice. Participants: Women with
      PCOS according to Rotterdam criteria; all former participants in the Metformin in
      Pregnant PCOS Women Study. Intervention: Metformin 2000 mg daily or placebo from
      first trimester to delivery in the original study. No intervention in the present
      follow-up study. Main Outcomes and Measures: Main outcome measure was weight gain
      in the follow-up period. Weight, body mass index (BMI), waist and hip
      circumferences, and blood pressure (BP) were registered. Body composition was
      assessed by bioelectrical impedance analysis, and fasting lipids, glucose, and
      insulin were analyzed. Results: Of 239 invited women, 131 (55%) participated in
      the follow-up. Weight gain was similar in women given metformin (2.1 +/- 10.5 kg)
      and women given placebo (1.8 +/- 11.2 kg) at 7.7 years' follow-up after pregnancy
      (P = 0.834). No difference was found in BMI, waist/hip ratio, BP, body
      composition, lipids, glucose and insulin levels, or prevalence of metabolic
      syndrome at follow-up between those treated with metformin and those treated with
      placebo during pregnancy. Conclusion: Metformin treatment during pregnancy did
      not influence the metabolic profile in women with PCOS at 7.7 years of follow-up.

PMID- 29659897
TI  - Additional Screening and Treatment of Malaria During Pregnancy Provides Further
      Protection Against Malaria and Nonmalarial Fevers During the First Year of Life.
AB  - Background: Although consensus exists that malaria in pregnancy (MiP) increases
      the risk of malaria in infancy, and eventually nonmalarial fevers (NMFs), there
      is a lack of conclusive evidence of benefits of MiP preventive strategies in
      infants. Methods: In Burkina Faso, a birth cohort study was nested to a clinical
      trial assessing the effectiveness of a community-based scheduled screening and
      treatment of malaria in combination with intermittent preventive treatment with
      sulfadoxine-pyrimethamine (CSST/IPTp-SP) to prevent placental malaria. Clinical
      episodes and asymptomatic infections were monitored over 1 year of follow-up to
      compare the effect of CSST/IPTp-SP and standard IPTp-SP on malaria and NMFs.
      Results: Infants born during low-transmission season from mothers receiving
      CSST/IPTp-SP had a 26% decreased risk of experiencing a first clinical episode
      (hazard ratio, 0.74 [95% confidence interval, .55-0.99]; P = .047). CSST/IPTp-SP
      interacted with birth season and gravidity to reduce the incidence of NMFs. No
      significant effects of CSST/IPTp-SP on the incidence of clinical episodes,
      parasite density, and Plasmodium falciparum infections were observed.
      Conclusions: Our findings indicate that CSST/IPTp-SP strategy may provide
      additional protection against both malaria and NMFs in infants during the first
      year of life, and suggest that malaria control interventions during pregnancy
      could have long-term benefits in infants.

PMID- 29659899
TI  - Reply to Rucinski et al.

PMID- 29659898
TI  - Cholesterol Metabolism Is Enhanced in the Liver and Brain of Children With Citrin
      Deficiency.
AB  - Context: Citrin-deficient infants present neonatal intrahepatic cholestasis
      caused by citrin deficiency (NICCD), which resolves at 12 months. Thereafter,
      they have normal liver function associated with hypercholesterolemia, and a
      preference for lipid-rich carbohydrate-restricted diets. However, some develop
      adult-onset type II citrullinemia, which is associated with metabolic
      abnormalities. Objectives: To identify the causes of hypercholesterolemia in
      citrin-deficient children post-NICCD. Design and Setting: We determined the
      concentrations of sterol markers of cholesterol synthesis, absorption, and
      catabolism by liquid chromatography-electrospray ionization-tandem mass
      spectrometry and evaluated serum lipoprotein profiles. Subjects: Twenty citrin
      deficient children aged 5 to 13 years and 37 age-matched healthy children.
      Intervention: None. Main Outcome Measures: Relationship between serum
      lipoproteins and sterol markers of cholesterol metabolism. Results: The citrin
      deficient group had a significantly higher high-density lipoprotein cholesterol
      (HDL-C) concentration than did the control group (78 +/- 11 mg/dL vs 62 +/- 14
      mg/dL, P < 0.001), whereas the two groups had similar low-density lipoprotein
      cholesterol and triglyceride concentrations. The concentrations of markers of
      cholesterol synthesis (lathosterol and 7-dehydrocholesterol) and bile acids
      synthesis (7alpha-hydroxycholesterol and 27-hydroxycholesterol) were 1.5- to 2.8
      fold and 1.5- to 3.9-fold, respectively, higher in the citrin-deficient group
      than in the control group. The concentration of 24S-hydroxycholesterol, a marker
      of cholesterol catabolism in the brain, was 2.5-fold higher in the citrin
      deficient group. In both groups, the HDL-C concentration was significantly
      positively correlated with that of 27-hydroxycholesterol, the first product of
      the alternative bile acid synthesis pathway. Conclusions: HDL-C and sterol marker
      concentrations are elevated in citrin-deficient children post-NICCD. Moreover,
      cholesterol synthesis and elimination are markedly enhanced in the liver and
      brain of citrin-deficient children.

PMID- 29659900
TI  - Monitoring of the Cowpea Bruchid, Callosobruchus maculatus (Coleoptera:
      Bruchidae), Feeding Activity in Cowpea Seeds: Advances in Sensing Technologies
      Reveals New Insights.
AB  - Cowpea provides a significant source of protein for over 200 million people in
      Sub-Saharan Africa. The cowpea bruchid, Callosobruchus maculatus (F) (Coleoptera:
      Bruchidae), is a major pest of cowpea as the larval stage attacks stored cowpea
      grains, causing postharvest loss. Cowpea bruchid larvae spend all their time
      feeding within the cowpea seed. Past research findings, published over 25 yr ago,
      have shown that feeding activity of several bruchids within a cowpea seed emit
      mechanical vibrations within the frequency range 5-75 kHz. This work led to the
      development of monitoring technologies that are both important for basic research
      and practical application. Here, we use newer and significantly improved
      technologies to re-explore the nature of the vibration signals produced by an
      individual C. maculatus, when it feeds in cowpea seeds. Utilizing broadband
      frequency sensing, individual fourth-instar bruchid larvae feeding activities
      (vibration events) were recorded to identify specific key emission frequencies.
      Verification of recorded events and association to actual feeding activities was
      achieved through mass measurements over 24 h for a series of replicates. The
      measurements identified variable peak event emission frequencies across the
      replicate sample set ranging in frequency from 16.4 to 26.5 kHz. A positive
      correlation between the number of events recorded and the measured mass loss of
      the cowpea seed was observed. The procedure and verification reported in this
      work provide an improved basis for laboratory-based monitoring of single larval
      feeding. From the rich dataset captured, additional analysis can be carried out
      to identify new key variables of hidden bruchid larval activity.

PMID- 29659901
TI  - Considerations on the Species Complex of the Cortelezzii series (Diptera:
      Psychodidae) and Description of Evandromyia chacuensis sp. nov., a New
      Phlebotomine Species of the Chaco Region, Argentina.
AB  - A new species of phlebotomine sand fly is described and illustrated based on male
      and female specimens collected in rural and semi-urban areas of the Chaco
      Province, Argentina. A separation of the Cortelezzii series in two species
      complexes is proposed, as is a species key for its identification. The
      morphological characters of the new species permit its inclusion in the
      Cortelezzii series of genus Evandromyia, subgenus Barrettomyia (Diptera:
      Psychodidae). The species is named Evandromyia chacuensis sp. nov. Szelag, Rosa,
      Galati, Andrade Fhilo & Salomon (Diptera: Psychodidae).

PMID- 29659902
TI  - Seasonal Reproductive Performance and Pre-diapausing Mating Status of Female
      Riptortus pedestris (Hemiptera: Alydidae) Collected in Fields.
AB  - Two unexplained phenomena are found in Riptortus pedestris (Fabricius)
      (Hemiptera: Alydidae): the first is that it tends to enter reproductive diapause
      much earlier in the season and to occur on host plants until late fall before
      finding hibernation site. The second is that they emerge in early spring when
      primary food sources such as leguminous plants are unavailable. To understand
      these phenological trends, the reproductive seasonality of both field-collected
      and laboratory-reared R. pedestris were compared under conditions of with/without
      food or access to mates. Females collected in spring or fall produced very few
      eggs in laboratory. But, when food sources were provided, all the bugs produced
      more eggs. Eggs also hatched normally except those produced by the females
      collected in fall. This indicates that females collected in the spring were
      already mated while those collected in the fall were not, most likely because
      they were in reproductive diapause. Similarly, when food was provided, all
      laboratory-reared bugs produced eggs, regardless of diapause status, with longer
      preoviposition period in diapausing bugs which might be due to the termination of
      reproductive diapause, but only eggs from mated females hatched. In conclusion,
      while spring reproduction (oviposition and egg hatch) of R. pedestris can occur
      in the presence of food resources, any lack of food can be limiting factor
      impeding these activities. In fall, reproduction is greatly reduced even when
      food resources are available, and under these conditions failure of females to
      become mated, due to reproductive diapause, is likely the limiting factor.

PMID- 29659903
TI  - Feasibility study of cancer genome alterations identified by next generation
      sequencing: ABC study.
AB  - Background: To confirm the feasibility and explore the clinical applicability of
      amplicon sequencing by next generation sequencing (NGS) of biopsy samples from
      patients with advanced solid tumors, we conducted a prospective study. Methods:
      Patients with unresectable, advanced, or recurrent solid tumors were included.
      Key eligibility criteria were as follows: 20 years or older, any planned systemic
      therapy, adequate lesion for biopsy, and written informed consent. Samples were
      fixed in 10% buffered formalin and embedded in paraffin. Cancer-derived DNA was
      extracted, and amplicon sequencing was performed using Ion AmpliseqTM Cancer
      Hotspot Panel version 1.0 or version 2.0 by central vendor. We evaluated the
      success rate of sequencing, and the proportion of the patients with actionable
      mutations. We organized an expert panel to share the results of targeted
      sequence, make annotations and reports, and discuss concomitant
      ethical/legal/social issues. Results: A total of 232 patients were included, and
      208 were successfully analyzed (success rate of 89.7%). The biopsy procedures
      were safe, with only one case of Grade 3 vasovagal reaction. The proportion of
      actionable/druggable mutations was 38.9% (81/208), which was not significantly
      different between the cancer panel version 1.0 and version 2.0 (P = 0.476).
      Expert panel could discuss the findings and make sufficient reports. Conclusions:
      We confirmed the feasibility of NGS-based amplicon sequencing using biopsy
      samples, making the basis for nationwide genome screening for cancer patients
      using biopsy samples. Our results suggest that focused panel may be sufficient to
      detect major mutations.

PMID- 29659905
TI  - Parasitism of Two Spodoptera spp. by Microplitis prodeniae (Hymenoptera:
      Braconidae).
AB  - Early instar larvae of the tobacco cutworm Spodoptera litura (Lepidoptera:
      Noctuidae) and the beet armyworm Spodoptera exigua (Lepidoptera: Noctuidae) are
      recognized hosts of the parasitic wasp Microplitis prodeniae Rao and Kurian
      (Hymenoptera: Braconidae), although M. prodeniae has previously been regarded as
      monophagous. In this study, we found the immature period and longevity of M.
      prodeniae developing in S. exigua was similar to that in S. litura. It was shown
      that the development time of M. prodeniae in S. exigua was 15.1 +/- 0.3 d, not
      significantly different from 15.0 +/- 0.2 d in S. litura. The parasitism rate of
      M. prodeniae attacking S. exigua was significantly lower than on S. litura (65.48
      +/- 2.29 and 43.83 +/- 2.20%, respectively), whilst the female ratio of the
      wasp's offspring was not significantly different when developing on the two
      species. M. prodeniae females prefer to oviposit on the second- and third-instar
      host larvae of S. exigua, rather than other instars. The effects of development
      of M. prodeniae on two important lepidopterous pests are discussed.

PMID- 29659904
TI  - Coinfection with Zika Virus (ZIKV) and Dengue Virus Results in Preferential ZIKV
      Transmission by Vector Bite to Vertebrate Host.
AB  - Background: Several tropical cities are permissive to Aedes aegypti and dengue
      virus (DENV) endemicity and have allowed for invasion and circulation of Zika
      virus (ZIKV) in the same areas. People living in arbovirus-endemic regions have
      been simultaneously infected with >=2 arboviruses. Methods: A. aegypti mosquitoes
      from Manaus, the capital city of Amazonas State in Brazil, were coinfected with
      circulating strains of DENV and ZIKV. The coinfected vectors were allowed to bite
      BALB/c mice. Results: A. aegypti from Manaus is highly permissive to
      monoinfection and coinfection with DENV and ZIKV and is capable of cotransmitting
      both pathogens by bite. Coinfection strongly influences vector competence,
      favoring transmission of ZIKV to the vertebrate host. Conclusions: This finding
      suggests that A. aegypti is an efficient vector of ZIKV and that ZIKV would be
      preferentially transmitted by coinfected A. aegypti. Coinfection in the vector
      population should be considered a new critical epidemiological factor and may
      represent a major public health challenge.

PMID- 29659906
TI  - Increased Chromogranin A-Positive Hormone-Negative Cells in Chronic Pancreatitis.
AB  - Context: Chronic pancreatitis (CP) is characterized by inflammation, fibrosis,
      and a loss of pancreatic acinar cells, which can result in exocrine and
      eventually endocrine deficiency. Pancreatitis has been reported to induce
      formation of new endocrine cells (neogenesis) in mice. Our recent data have
      implicated chromogranin A-positive hormone-negative (CPHN) cells as potential
      evidence of neogenesis in humans. Objective: We sought to establish if CPHN cells
      were more abundant in CP in humans. Design, Setting, and Participants: We
      investigated the frequency and distribution of CPHN cells and the expression of
      the chemokine C-X-C motif ligand 10 (CXCL10) and its receptor chemokine C-X-C
      motif receptor 3 in pancreas of nondiabetic subjects with CP. Results: CPHN cell
      frequency in islets was increased sevenfold in CP [2.1% +/- 0.67% vs 0.35% +/-
      0.09% CPHN cells in islets, CP vs nonpancreatitis (NP), P < 0.01], as were the
      CPHN cells found as scattered cells in the exocrine areas (17.4 +/- 2.9 vs 4.2 +/
      0.6, CP vs NP, P < 0.001). Polyhormonal endocrine cells were also increased in
      CP (2.7 +/- 1.2 vs 0.1 +/- 0.04, CP vs NP, % of polyhormonal cells of total
      endocrine cells, P < 0.01), as was expression of CXCL10 in alpha and beta cells.
      Conclusion: There is increased islet endogenous expression of the inflammation
      marker CXCL10 in islets in the setting of nondiabetic CP and an increase in
      polyhormonal (insulin-glucagon expressing) cells. The increase in CPHN cells in
      CP, often in a lobular distribution, may indicate foci of attempted endocrine
      cell regeneration.

PMID- 29659907
TI  - Effect of Cold Storage on Biological Traits of Psix saccharicola (Hymenoptera:
      Platygastridae), an Egg Parasitoid of Acrosternum arabicum (Hemiptera:
      Pentatomidae).
AB  - Psix saccharicola (Mani) (Hymenoptera: Platygastridae) is a solitary egg
      parasitoid of the pistachio green stink bug, Acrosternum arabicum (Wagner)
      (Hemiptera: Pentatomidae), which is one of the most important pests of pistachio
      in Iran. Augmentation of P. saccharicola field populations using mass-reared
      individuals may provide an alternative to conventional pesticide use for
      pistachio green stink bug control. Cold storage is an important component of mass
      rearing protocols for optimum timing of host egg parasitization and potentially
      extended storage of P. saccharicola pupae prior to adult emergence. The impact of
      cold storage on A. arabicum eggs for various time intervals at 4.0 degrees C was
      investigated. Results indicated that host eggs stored at 4.0 degrees C for up to
      60 d could be exploited by P. sacchricola, whereas no offspring were produced
      when eggs were stored for 120 d. The emergence rates of the F1 and F2 generations
      declined with increased host egg storage time. Both sex ratio and survival rate
      of the F2 generation decreased as the refrigeration time of host eggs increased.
      The impact of cold storage on P. saccharicola pupae was evaluated. Reared pupae
      of P. saccharicola were held for 1 wk at three temperatures and compared with a
      control (27 +/- 1 degrees C). Psix saccharicola pupae were tolerant to cold
      storage at 8 and 12 degrees C. Cold storage adversely affected mean adult
      emergence at 4 degrees C, which decreased following low temperature exposure.
      Furthermore, mean percentage survivorship was unaffected by storage at low
      temperatures in the F1 generation, but was reduced at 4 degrees C. The sex ratio
      of the F1 generation became more male-biased when held at lower storage
      temperatures. The highest female proportion was observed at 12 degrees C.

PMID- 29659908
TI  - Prototheca zopfii Colitis in Inherited CARD9 Deficiency.
AB  - Human protothecosis is a rare microalgae infection, and its dissemination
      typically occurs in immunocompromised individuals, but no specific immune defect
      has been reported. Here, we describe an 8-year-old daughter of a consanguineous
      union with abdominal pain and bloody diarrhea for 3 months who was found to have
      pancolitis with numerous microalgae identified as Prototheca zopfii. In the
      absence of a known immunodeficiency, exome sequencing was performed, which
      uncovered a novel recessive frameshift mutation in CARD9 (p.V261fs). This report
      highlights that CARD9 deficiency should be investigated in patients with
      unexplained systemic/visceral protothecosis and suggests a new mechanistic
      insight into anti-Prototheca immunity.

PMID- 29659909
TI  - Sexually Transmitted Bedfellows: Exquisite Association Between HIV and Herpes
      Simplex Virus Type 2 in 21 Communities in Southern Africa in the HIV Prevention
      Trials Network 071 (PopART) Study.
AB  - Background: Human immunodeficiency virus (HIV) and herpes simplex virus type 2
      (HSV2) are strongly associated, although mechanisms are not fully understood. An
      HIV prevention trial allowed reexamination of this association at individual and
      community levels. Methods: The HIV Prevention Trials Network 071 (PopART) study
      evaluates a combination prevention intervention in 21 urban communities in Zambia
      and South Africa. To measure impact on HIV infection incidence, a cohort of
      approximately 2000 adults (age range, 18-44 years) was selected randomly from
      each community. Baseline data on sociodemographic characteristics, behavior, and
      HIV/HSV2 serologic findings were used to examine the association between HIV and
      HSV2. At the community level, HIV prevalence was plotted against HSV2 prevalence.
      Results: A total of 38691 adults participated. HSV2 prevalence among women and
      men was 50% and 22%, respectively, in Zambia and 60% and 27%, respectively, in
      South Africa. Estimated HSV2 infection incidence among those aged 18-24 years was
      8.06 cases/100 person-years (95% confidence interval [CI], 6.76-9.35) and 1.76
      cases/100 person-years (95% CI, 1.30-2.22) among women and men, respectively. A 6
      fold higher odds of HIV infection was seen in HSV2-infected individuals in both
      sexes, after adjustment for confounders (odds ratio, 6.66 [95% CI, 6.07-7.31]
      among women and 6.57 [95% CI, 5.56-7.77] among men). At the community-level,
      there was a strong linear relationship between HIV and HSV2 prevalence (rho =
      0.92; P < .001). Conclusions: There was an exquisite association between these 2
      infections, at the individual and community levels, likely due in part to a
      powerful cofactor effect of HSV2 on HIV transmission. HSV2 control could
      contribute to HIV prevention.

PMID- 29659911
TI  - Comparative Bio-Efficacy and Synergism of New Generation Polyfluorobenzyl and
      Conventional Pyrethroids Against Culex quinquefasciatus (Diptera: Culicidae).
AB  - Intensive exposure to insecticides has resulted in the evolution of insecticide
      resistance in the mosquitoes. We tested the bio-efficacy of two Culex
      quinquefasciatus Say (Diptera: Culicidae) laboratory strains differentially bio
      responsive to pyrethroids to understand the comparative efficacy of different
      polyfluorobenzyle and conventional pyrethroid molecules and the role of piperonyl
      butoxide (PBO) in synergizing these molecules in increased tolerance of
      mosquitoes to these molecules. We have taken deltamethrin (alpha-cyano pyrethroid
      with phenoxybenzyl moiety); permethrin (phenoxybenzyl pyrethroid without an alpha
      cyano group); transfluthrin, dimefluthrin, metofluthrin, and meperfluthrin
      (polyfluorinated benzyl compounds); and prallethrin (modified cyclopentadienone
      compound) for this study. We found higher bio-efficacy in dimefluthrin,
      metofluthrin, and meperfluthrin compared with transfluthrin against tested
      mosquito strains. We found that transfluthrin exhibited synergism with PBO, which
      supports the hypothesis that P450 enzymes could play a role in the detoxification
      process of transfluthrin, which was earlier not believed. However, other
      polyfluorobenzyl pyrethroids with a 4-(methoxymethyl) phenyl capping in the
      tetrafluorobenzyl ring (dimefluthrin, metofluthrin, and meperfluthrin) exhibit
      greater synergism with PBO compared with transfluthrin. Further study is required
      to understand the mechanism for higher synergistic ratios in polyfluorobenzyl
      pyrethroids with 4-(methoxymethyl) phenyl moiety and ascertain the possible
      involvement of novel mechanisms that may involve in developing resistance. This
      is the first report of comparative bio-efficacy of multiple polyfluorobenzyl
      pyrethroids and PBO synergism against mosquitoes.

PMID- 29659910
TI  - Household Transmission of Ebola Virus: Risks and Preventive Factors, Freetown,
      Sierra Leone, 2015.
AB  - Background: Knowing risk factors for household transmission of Ebola virus is
      important to guide preventive measures during Ebola outbreaks. Methods: We
      enrolled all confirmed persons with Ebola who were the first case in a household,
      December 2014-April 2015, in Freetown, Sierra Leone, and their household
      contacts. Cases and contacts were interviewed, contacts followed prospectively
      through the 21-day incubation period, and secondary cases confirmed by laboratory
      testing. Results: We enrolled 150 index Ebola cases and 838 contacts; 83 (9.9%)
      contacts developed Ebola during 21-day follow-up. In multivariable analysis, risk
      factors for transmission included index case death in the household, Ebola
      symptoms but no reported fever, age <20 years, more days with wet symptoms; and
      providing care to the index case (P < .01 for each). Protective factors included
      avoiding the index case after illness onset and a piped household drinking water
      source (P < .01 for each). Conclusions: To reduce Ebola transmission, communities
      should rapidly identify and follow-up all household contacts; isolate those with
      Ebola symptoms, including those without reported fever; and consider closer
      monitoring of contacts who provided care to cases. Households could consider
      efforts to minimize risk by designating one care provider for ill persons with
      all others avoiding the suspected case.

PMID- 29659912
TI  - Turning Off the Tap: Using the FAST Approach to Stop the Spread of Drug-Resistant
      Tuberculosis in the Russian Federation.
AB  - Background: We report the association of the FAST strategy (find cases actively,
      separate safely, and treat effectively) with reduction of hospital-based
      acquisition of multidrug-resistant tuberculosis in the Russian Federation.
      Methods: We used preintervention and postintervention cohorts in 2 Russian
      hospitals to determine whether the FAST strategy was associated with a reduced
      odds of converting MDR tuberculosis within 12 months among patients with
      tuberculosis susceptible to isoniazid and rifampin at baseline. Results: Sixty
      three of 709 patients (8.9%) with isoniazid and rifampin-susceptible tuberculosis
      acquired MDR tuberculosis; 55 (12.2%) were in the early cohort, and 8 (3.1%) were
      in the FAST cohort. The FAST strategy was associated with a reduced odds
      (adjusted odds ratio, 0.16; 95% confidence interval, .07-.39) and 9.2% absolute
      reduction in the risk of MDR tuberculosis acquisition. Conclusion: Use of the
      FAST strategy in 2 Russian hospitals was associated with significantly less MDR
      tuberculosis 12 months after implementation.

PMID- 29659913
TI  - A randomized, double-blind, non-inferiority study of hydromorphone hydrochloride
      immediate-release tablets versus oxycodone hydrochloride immediate-release powder
      for cancer pain: efficacy and safety in Japanese cancer patients.
AB  - Background: Hydromorphone is a standard opioid analgesic for cancer pain that,
      prior to this study, was not approved in Japan, where options for opioid
      switching are limited. We aimed to investigate the efficacy and safety of
      hydromorphone (DS-7113b) immediate-release tablets in opioid-naive cancer
      patients with moderate to severe cancer pain. Methods: Multicenter, active
      controlled, randomized, double-blind, parallel-group, non-inferiority study of
      183 cancer patients over 20 years of age at 50 clinical sites in Japan.
      Hydromorphone tablets or oxycodone hydrochloride powder was orally administered
      four times daily for 5 days. The initial doses of hydromorphone and oxycodone
      hydrochloride were 4 mg/day and 10 mg/day, respectively, and adjusted as
      necessary. Efficacy was evaluated as the intergroup difference (95% confidence
      interval [CI]) of the least squares mean by analysis of covariance, using the
      baseline visual analog scale (VAS) as a covariate for change in VAS score at
      treatment completion/discontinuation in the full analysis set. Results: Non
      inferiority of hydromorphone versus oxycodone was confirmed, with an intergroup
      difference (95% CI) in the least squares mean of -3.4 mm (-9.8 to 3.1 mm) for
      change in VAS scores, which was below the upper limit of the 95% CI at 10 mm, the
      non-inferiority limit determined during study planning. Adverse events occurred
      in 83.0% (73/88) of patients in the hydromorphone group and 77.4% (65/84) in the
      oxycodone group. The most frequently observed adverse events were somnolence,
      constipation, vomiting and nausea. Conclusions: The efficacy and safety of
      hydromorphone tablets are equivalent to those of oxycodone immediate-release
      powder.

PMID- 29659914
TI  - Cognitive Abilities Moderate the Effect of Disease Severity on Health-Related
      Quality of Life in Pediatric Sickle Cell Disease.
AB  - Objective: Complications that can arise from sickle cell disease (SCD) have the
      potential to negatively affect health-related quality of life (HRQL). SCD
      manifests in varying degrees of severity, but effects on HRQL are not uniform.
      Cognitive abilities influence HRQL in other pediatric groups, potentially through
      variability in treatment adherence and psychological coping. This study examined
      the effect of SCD severity on HRQL and explored cognitive abilities as a
      moderator of this relationship. Methods: A total of 86 children and adolescents
      with SCD (ages 7-16 years) completed a cognitive assessment (Wechsler Scale of
      Intelligence for Children, Fifth Edition), and primary caregivers rated their
      child's SCD severity and HRQL (PedsQL Sickle Cell Disease Module). A hierarchical
      linear regression was conducted to evaluate the interactive effect of SCD
      severity and cognitive functioning on HRQL. Results: Caregiver-rated SCD severity
      predicted HRQL and cognitive abilities interacted with disease severity to
      influence HRQL. Youth with milder SCD and cognitive abilities in the average
      range or higher demonstrated significantly better HRQL compared with youth with
      mild SCD but below average cognitive abilities. Youth with more severe disease
      appeared to exhibit similarly low levels of HRQL, with only a minimal influence
      of cognitive abilities. Conclusions: Cognitive factors modify the effect of SCD
      severity on HRQL, particularly among youth with milder forms of SCD. Future
      studies are warranted to clarify the role of cognitive abilities in determining
      HRQL. Clinicians should monitor youth with milder forms of SCD and limited
      cognitive abilities for worsening HRQL and opportunities to provide support
      around disease self-management.

PMID- 29659915
TI  - Temperature Alters the Response to Insecticides in Drosophila suzukii (Diptera:
      Drosophilidae).
AB  - Drosophila suzukii Matsumura (Diptera: Drosophilidae) is an invasive pest in
      Europe and is a major threat to the soft fruit industry. Because of an ample
      temperature range, the pest spans from low to high elevation crops in mountain
      areas of the Southern Alps. Starting from field observations on the variable
      efficacy of insecticides under different temperatures, experiments were designed
      to test the efficacy of chemical families of insecticides available against this
      pest. Pyrethroids and spynosins proved to be the most effective under all
      temperature conditions (14, 22, and 30 degrees C) in all assays. Organophosphates
      and neonicotinoids showed significantly lower efficacy at low temperatures,
      indicating that they are not suitable to protect crops under those conditions.
      The management of the pest in cold habitats, which are suitable for the
      cultivation of high-quality berries as for example in mountain farming systems,
      is constrained by a limited number of molecules available for fruit protection.
      Temperature has to be considered among factors affecting the decision-making
      process for the choice of registered formulations to be used in pest control.

PMID- 29659917
TI  - Jumonji domain-containing protein family: the functions beyond lysine
      demethylation.

PMID- 29659918
TI  - Association of dairy intake with weight change in adolescents undergoing obesity
      treatment.
AB  - Background: The role of dairy products in obesity treatment for adolescents is
      unclear. The study purpose was to assess the association between dairy intake and
      changes in BMI z-score (zBMI) during adolescent obesity treatment. Methods:
      Observational study nested within a randomized control trial. Linear mixed
      effects regression models were adjusted for important non-lifestyle factors then
      further adjusted for dietary and physical activity variables. In total, 91
      adolescents were studied. Results: Each serving of total dairy (beta = -0.0054, P
      < 0.01), unflavored milk (beta = -0.012, P < 0.01), reduced fat (beta = -0.0078,
      P < 0.05), and low fat/fat-free products (beta = -0.0149, P < 0.01) was
      associated with a decrease in zBMI over 12 months. These associations were no
      longer significant after adjustment for other dietary and physical activity
      factors. Sugar-sweetened beverage intake was inversely associated with intake of
      total dairy (beta = -0.186, P = 0.001), unflavored milk (beta = -0.115, P =
      0.003) and low fat/fat-free dairy (beta = -0.125, P = 0.001). Conclusions:
      Intakes of total dairy, unflavored milk, reduced fat dairy and low fat/fat-free
      dairy products are associated with improved obesity treatment outcomes among
      adolescents. This could be due to co-occurring healthy lifestyle behaviors or to
      replacement of other food and beverages associated with obesity, such as sugar
      sweetened beverages, by dairy products.

PMID- 29659916
TI  - Human Gut Microbiota Predicts Susceptibility to Vibrio cholerae Infection.
AB  - Background: Cholera is a public health problem worldwide, and the risk factors
      for infection are only partially understood. Methods: We prospectively studied
      household contacts of patients with cholera to compare those who were infected to
      those who were not. We constructed predictive machine learning models of
      susceptibility, using baseline gut microbiota data. We identified bacterial taxa
      associated with susceptibility to Vibrio cholerae infection and tested these taxa
      for interactions with V. cholerae in vitro. Results: We found that machine
      learning models based on gut microbiota, as well as models based on known
      clinical and epidemiological risk factors, predicted V. cholerae infection. A
      predictive gut microbiota of roughly 100 bacterial taxa discriminated between
      contacts who developed infection and those who did not. Susceptibility to cholera
      was associated with depleted levels of microbes from the phylum Bacteroidetes. By
      contrast, a microbe associated with cholera by our modeling framework, Paracoccus
      aminovorans, promoted the in vitro growth of V. cholerae. Gut microbiota
      structure, clinical outcome, and age were also linked. Conclusion: These findings
      support the hypothesis that abnormal gut microbial communities are a host factor
      related to V. cholerae susceptibility.

PMID- 29659919
TI  - Response to Hashiguchi and Gomez (2018).

PMID- 29659921
TI  - Co-circulation of Flanders Virus and West Nile Virus in Culex Mosquitoes
      (Diptera: Culicidae) from Chicago, Illinois.
AB  - West Nile virus (WNV) and Flanders virus (FLAV) co-occur in regions of North
      America. Because both viruses are maintained in a transmission cycle involving
      Culex mosquitoes and birds, screening mosquitoes for FLAV has been suggested as
      an enhancement to WNV surveillance and epidemic prediction. Using samples
      collected in 2010 and 2012 in Chicago, IL, USA, we demonstrate the presence of
      FLAV in four out of 287 (1.4%) Culex pools. We estimated minimum infection rates
      for WNV and FLAV to be 5.66 and 1.22 in 2010 and 8.74 and 0.61 in 2012,
      respectively. FLAV occurred 1 and 3 wk prior to the peak of WNV transmission in
      2010 and 2012, respectively. FLAV sequences from Chicago were genetically diverse
      and phylogenetically representative of lineage A viruses from across the United
      States.

PMID- 29659922
TI  - Chronology of the Intrapuparial Development of the Blowfly Chrysomya albiceps
      (Diptera: Calliphoridae): Application in Forensic Entomology.
AB  - Insects display different patterns of development, and blow flies have one of the
      most specialized patterns of intrapuparial development of all. In forensic
      entomology, pupae can be used as a tool to estimate the minimum postmortem time
      interval (minPMI). We analyzed the intrapuparial development of Chrysomya
      albiceps (Diptera: Caloricidade), whose larvae had been fed pig lungs and reared
      in a climate-controlled room at 28 degrees C day/26 degrees C night, 70 +/- 10%
      RH, and 12 h of photophase and monitored daily. After the third-instar larvae
      abandoned their diet, the process of pupariation and pupation was monitored. At
      pre-established times, five pupae were collected, euthanized, and fixed in 5%
      formaldehyde, inside polypropylene test tubes with caps. Since they were the
      first, they were classified as 0 h pupae. Twelve collections occurred until the
      emergence of the adults, at 0, 2, 4, 6, 8, 10, 24, 30, 48, 54, 72, 78, 96, and 99
      h (n = 84). The fixed pupae were dissected under the microscope, with the aid of
      anatomical tweezers and hypodermic needles, and photographed. The stages of
      metamorphosis and the morphological alterations occurring during the process were
      identified, described, and recorded before and after pupation. These phases were:
      pupation, larval pupal apolysis, cryptocephalic, phanerocephalic, pharate adult,
      emergence, and adult. The cryptophalic phase occurred between 4 and 6 h after
      pupation; the phanerocephalic phase between 6 and 10 h after; the pharate adult
      phase between 24 and 96 h after; and the imago/emergence phase 99 h after
      pupation.

PMID- 29659920
TI  - Chromosome 14q32.2 Imprinted Region Disruption as an Alternative Molecular
      Diagnosis of Silver-Russell Syndrome.
AB  - Context: Silver-Russell syndrome (SRS) (mainly secondary to 11p15 molecular
      disruption) and Temple syndrome (TS) (secondary to 14q32.2 molecular disruption)
      are imprinting disorders with phenotypic (prenatal and postnatal growth
      retardation, early feeding difficulties) and molecular overlap. Objective: To
      describe the clinical overlap between SRS and TS and extensively study the
      molecular aspects of TS. Patients: We retrospectively collected data on 28
      patients with disruption of the 14q32.2 imprinted region, identified in our
      center, and performed extensive molecular analysis. Results: Seventeen (60.7%)
      patients showed loss of methylation of the MEG3/DLK1 intergenic differentially
      methylated region by epimutation. Eight (28.6%) patients had maternal uniparental
      disomy of chromosome 14 and three (10.7%) had a paternal deletion in 14q32.2.
      Most patients (72.7%) had a Netchine-Harbison SRS clinical scoring system >=4/6,
      and consistent with a clinical diagnosis of SRS. The mean age at puberty onset
      was 7.2 years in girls and 9.6 years in boys; 37.5% had premature pubarche. The
      body mass index of all patients increased before pubarche and/or the onset of
      puberty. Multilocus analysis identified multiple methylation defects in 58.8% of
      patients. We identified four potentially damaging genetic variants in genes
      encoding proteins involved in the establishment or maintenance of DNA
      methylation. Conclusions: Most patients with 14q32.2 disruption fulfill the
      criteria for a clinical diagnosis of SRS. These clinical data suggest similar
      management of patients with TS and SRS, with special attention to their young age
      at the onset of puberty and early increase of body mass index.

PMID- 29659923
TI  - A Nonsynonymous Variant in the GOLM1 Gene in Cutaneous Malignant Melanoma.
AB  - Background: Statistically significant linkage of melanoma to chromosome 9q21 was
      previously reported in a Danish pedigree resource and independently confirmed in
      Utah high-risk pedigrees, indicating strong evidence that this region contains a
      melanoma predisposition gene. Methods: Whole-exome sequencing of pairs of related
      melanoma case subjects from two pedigrees with evidence of 9q21 linkage was
      performed to identify the responsible predisposition gene. Candidate variants
      were tested for association with melanoma in an independent set of 454 unrelated
      familial melanoma case subjects and 396 unrelated cancer-free control subjects
      from Utah, and 1534 melanoma case subjects and 1146 noncancer control subjects
      from Texas (MD Anderson) via a two-sided Fisher exact test. Results: A rare
      nonsynonymous variant in Golgi Membrane Protein 1 (GOLM1), rs149739829, shared in
      two hypothesized predisposition carriers in one linked pedigree was observed.
      Segregation of this variant in additional affected relatives of the index
      carriers was confirmed. A statistically significant excess of carriers of the
      variant was observed among Utah case subjects and control subjects (odds ratio
      [OR] = 9.81, 95% confidence interval [CI] = 8.35 to 11.26, P < .001) and
      statistically significantly confirmed in Texas case subjects and control subjects
      (OR = 2.45, 95% CI = 1.65 to 3.25, P = .02). Conclusion: These findings support
      GOLM1 as a candidate melanoma predisposition gene.

PMID- 29659925
TI  - Tobacco Smoking-Associated Alterations in the Immune Microenvironment of Squamous
      Cell Carcinomas.
AB  - Background: Tobacco smoking creates DNA damage, inducing mutations and
      potentially altering the tumor immune microenvironment. These types of genetic
      and immune microenvironment alterations are critical factors known to affect
      tumor response to immunotherapy. Here we analyze the association between the
      mutational signature of tobacco smoking, tumor mutational load, and metrics of
      immune activity in squamous cell carcinomas arising in the head and neck and
      lung. Methods: Using RNA and DNA sequencing data from The Cancer Genome Atlas
      head and neck (HNSC; n = 287) and lung (LUSC; n = 130) squamous cell carcinoma
      data sets and two independent gene expression data sets (HNSC, n = 136; LUSC, n =
      75), we examined associations between the mutational smoking signature, mutation
      count, immune cell infiltration, cytolytic activity, and interferon-gamma
      signaling. Results: An increasing mutational smoking signature was associated
      with statistically significantly increased overall mutational load in both HNSC
      (rho = .33, P = 1.01 * 10-7) and LUSC (rho = .49, P = 2.80 * 10-9). In HNSC, a
      higher mutational smoking signature was associated with lower levels of immune
      infiltration (rho = -.37, P = 1.29 * 10-10), cytolytic activity (rho = -.28, P =
      4.07 * 10-6), and interferon-gamma pathway signaling (rho = .39, P = 3.20 * 10
      11). In LUSC, these associations were reversed (rho = .19, P = .03; rho = .20, P
      = .02; and rho = .18, P = .047, respectively). Differentially expressed genes
      between smoking-high and smoking-low tumors revealed broad tobacco-induced
      immunosuppression in HNSC, in contrast to a tumor-inflamed microenvironment in
      smokers with LUSC. Conclusions: In squamous cell carcinomas, the genetic smoking
      signature is associated with higher mutational load, but variable effects on
      tumor immunity can occur, depending on anatomic site. In HNSC, smoking is
      predominantly immunosuppressive; in LUSC, more pro-inflammatory. Both tumor
      mutation load and immune microenvironment affect clinical response to
      immunotherapy. Thus, the mutational smoking signature is likely to have relevance
      for immunotherapeutic investigation in smoking-associated cancers.

PMID- 29659924
TI  - Evaluation of a Booster Dose of Pentavalent Rotavirus Vaccine Coadministered With
      Measles, Yellow Fever, and Meningitis A Vaccines in 9-Month-Old Malian Infants.
AB  - Background: Rotavirus vaccines given to infants are safe and efficacious. A
      booster dose of rotavirus vaccine could extend protection into the second year of
      life in low-resource countries. Methods: We conducted an open-label, individual
      randomized trial in Bamako, Mali. We assigned 600 infants aged 9-11 months to
      receive measles vaccine (MV), yellow fever vaccine (YFV), and meningococcal A
      conjugate vaccine (MenAV) with or without pentavalent rotavirus vaccine (PRV). We
      assessed the noninferiority (defined as a difference of <=10%) of seroconversion
      and seroresponse rates to MV, YFV, and MenAV. We compared the seroresponse to
      PRV. Results: Seroconversion to MV occurred in 255 of 261 PRV recipients (97.7%)
      and 246 of 252 control infants (97.6%; difference, 0.1% [95% confidence interval
      {CI}, -4.0%-4.2%]). Seroresponse to YFV occurred in 48.1% of PRV recipients (141
      of 293), compared with 52.2% of controls (153 of 293; difference, -4.1% [95% CI, 
      12.2%-4.0%]). A 4-fold rise in meningococcus A bactericidal titer was observed in
      273 of 292 PRV recipients (93.5%) and 276 of 293 controls (94.2%; difference, 
      0.7% [95% CI, -5.2%-3.8%]). Rises in geometric mean concentrations of
      immunoglobulin A and immunoglobulin G antibodies to rotavirus were higher among
      PRV recipients (118 [95% CI, 91-154] and 364 [95% CI, 294-450], respectively),
      compared with controls (68 [95% CI, 50-92] and 153 [95% CI, 114-207],
      respectively). Conclusions: PRV did not interfere with MV and MenAV; this study
      could not rule out interference with YFV. PRV increased serum rotavirus antibody
      levels. Clinical Trials Registration: NCT02286895.

PMID- 29659926
TI  - Evidence-based cancer prevention recommendations for Japanese.
AB  - A comprehensive evidence-based cancer prevention recommendation for Japanese was
      developed. We evaluated the magnitude of the associations of lifestyle factors
      and infection with cancer through a systematic review of the literature, meta
      analysis of published data, and pooled analysis of cohort studies in Japan. Then,
      we judged the strength of evidence based on the consistency of the associations
      between exposure and cancer and biological plausibility. Important factors were
      extracted and summarized as an evidence-based, current cancer prevention
      recommendation: 'Cancer Prevention Recommendation for Japanese'. The
      recommendation addresses six important domains related to exposure and cancer,
      including smoking, alcohol drinking, diet, physical activity, body weight and
      infection. The next step should focus on the development of effective behavior
      modification programs and their implementation and dissemination.

PMID- 29659927
TI  - H1N1pdm09 Influenza Virus and Its Descendants Lack Extra-epitopic Amino Acid
      Residues Associated With Reduced Recognition by M158-66-Specific CD8+ T Cells.
AB  - Extra-epitopic amino acid residues affect recognition of human influenza A
      viruses (IAVs) by CD8+ T-lymphocytes (CTLs) specific for the highly conserved HLA
      A*0201 restricted M158-66 epitope located in the matrix 1 (M1) protein. These
      residues are absent in the M1 protein of the 2009-pandemic IAV (H1N1pdm09).
      Consequently, stimulation with M1 protein of H1N1pdm09 IAV resulted in stronger
      activation and lytic activity of M158-66-specific CTLs than stimulation with
      seasonal H3N2 IAVs. During >6 years of circulation in the human population,
      descendants of the H1N1pdm09 virus had accumulated 4 other amino acid
      substitutions. However, these did not affect M158-66-specific CTL activation.

PMID- 29659928
TI  - Detection of Aedes (Stegomyia) aegypti (Diptera: Culicidae) Populations in
      Southern Alabama Following a 26-yr Absence and Public Perceptions of the Threat
      of Zika Virus.
AB  - With the establishment of Zika virus in the Americas, an accurate understanding
      of the geographic range of its primary vector, Aedes (Stegomyia) aegypti (L.)
      (Diptera: Culicidae), is vital to assessing transmission risk. In an article
      published in June 2016, Hahn and colleagues compiled county-level records in the
      United States for the presence of Ae. aegypti and Aedes (Stegomyia) albopictus
      (Skuse) (Diptera: Culicidae) reported between January 1995 and March 2016.
      Despite ecological suitability for both mosquito species along the Gulf Coast,
      Ae. aegypti was not reported in Alabama during the time interval, a result
      consistent with research suggesting that interactions between these two species
      often result in displacement of Ae. aegypti. Herein, we report the detection of
      Ae. aegypti populations in Mobile, Alabama, after a 26-yr absence and present
      findings on human perceptions of Zika virus relevant to transmission. It is
      unclear whether the specimens (69 out of 1074) represent a recent re-introduction
      or belong to a previously undetected remnant population. Sequencing of mtDNA from
      identified Ae. aegypti matched closest to a specimen collected in Kerala, India.
      A survey of residents in the surveillance area suggests high encounter rates with
      mosquitoes in and around homes. Despite high self-reported knowledge about Zika
      virus, the survey revealed gaps in knowledge regarding its transmission cycle and
      relative degrees of vulnerability to serious illness among segments of the human
      population. These findings highlight the importance of continued surveillance,
      vector control, and public-health education in Gulf Coast states, as well as the
      potential threat of Ae. Aegypti-transmitted pathogens in southern Alabama.

PMID- 29659929
TI  - Cross-associations between physical activity and sedentary time on metabolic
      health: a comparative assessment using self-reported and objectively measured
      activity.
AB  - Purpose: Physical activity and sedentary time have distinct physiologic and
      metabolic effects, but little is known about their joint associations. Methods:
      The Canadian Health Measures Survey (n = 5950) was used to (i) examine the joint
      relationship between active/non-sedentary (referent group), active/sedentary,
      inactive/non-sedentary and inactive/sedentary phenotypes on obesity and metabolic
      health; and (ii) compare these relationships when using objective (accelerometer)
      total activity or subjective (self-report) leisure-time measures. Weighted
      associations for the metabolic syndrome (MetS), individual MetS components, 1+
      disease (1 or more of diabetes, myocardial infarction, stroke, cardiovascular
      disease) and obesity were estimated using logistic regression. Results: After
      adjustments, the odds (OR, 95% CI) of 1+ disease (OR = 3.05, 1.47-6.34) and
      abdominal obesity (OR = 2.75, 1.16-6.55) were higher in the inactive/sedentary
      group versus the referent group (OR = 1.00) when measured objectively. Within
      self-report leisure-time groups, elevated odds were observed for the
      inactive/sedentary group for MetS, obesity, abdominal obesity and elevated
      triglycerides. Inactive/non-sedentary and active/sedentary groups were similarly
      protective when measured by accelerometer. Conclusion: Using accelerometer data,
      the inactive/sedentary group was at higher risk for 1+ disease and abdominal
      obesity only, whereas the active/sedentary and inactive/non-sedentary groups were
      not at higher risk for any health outcome.

PMID- 29659930
TI  - Automated Cervical Screening and Triage, Based on HPV Testing and Computer
      Interpreted Cytology.
AB  - Background: State-of-the-art cervical cancer prevention includes human
      papillomavirus (HPV) vaccination among adolescents and screening/treatment of
      cervical precancer (CIN3/AIS and, less strictly, CIN2) among adults. HPV testing
      provides sensitive detection of precancer but, to reduce overtreatment, secondary
      "triage" is needed to predict women at highest risk. Those with the highest-risk
      HPV types or abnormal cytology are commonly referred to colposcopy; however,
      expert cytology services are critically lacking in many regions. Methods: To
      permit completely automatable cervical screening/triage, we designed and
      validated a novel triage method, a cytologic risk score algorithm based on
      computer-scanned liquid-based slide features (FocalPoint, BD, Burlington, NC). We
      compared it with abnormal cytology in predicting precancer among 1839 women
      testing HPV positive (HC2, Qiagen, Germantown, MD) in 2010 at Kaiser Permanente
      Northern California (KPNC). Precancer outcomes were ascertained by record
      linkage. As additional validation, we compared the algorithm prospectively with
      cytology results among 243 807 women screened at KPNC (2016-2017). All
      statistical tests were two-sided. Results: Among HPV-positive women, the
      algorithm matched the triage performance of abnormal cytology. Combined with
      HPV16/18/45 typing (Onclarity, BD, Sparks, MD), the automatable strategy referred
      91.7% of HPV-positive CIN3/AIS cases to immediate colposcopy while deferring
      38.4% of all HPV-positive women to one-year retesting (compared with 89.1% and
      37.4%, respectively, for typing and cytology triage). In the 2016-2017
      validation, the predicted risk scores strongly correlated with cytology (P <
      .001). Conclusions: High-quality cervical screening and triage performance is
      achievable using this completely automated approach. Automated technology could
      permit extension of high-quality cervical screening/triage coverage to currently
      underserved regions.

PMID- 29659932
TI  - Effects of Bacterial Dose and Fly Sex on Persistence and Excretion of Salmonella
      enterica serovar Typhimurium From Adult House Flies (Musca domestica L.; Diptera:
      Muscidae).
AB  - Salmonella Typhimurium (Le Minor and Popoff 1987; Enterobacteriales:
      Enterobacteriaceae) is a pathogen that causes gastroenteritis in humans and can
      be harbored by house flies. Factors influencing excretion of S. Typhimurium from
      infected flies have not been elucidated but are essential for assessing
      transmission potential. We determined the persistence and excretion of a green
      fluorescent protein (GFP) expressing strain of S. Typhimurium from house flies.
      Individual male and female flies were fed either sterile Luria-Bertani (LB) broth
      (controls) or cultures of "high" (~105 colony forming units [CFU]) or "low" (~104
      CFU) doses of bacteria (treatments). Bacterial persistence was determined over 16
      h by culturing whole-fly homogenate. Both sex and dose affected persistence
      between 6 and 12 h postingestion. In a separate experiment, fly excretion events
      were monitored during this time interval and excreta droplets were individually
      cultured for bacteria. Female flies had more excretion events than males across
      treatments. We observed interactions of fly sex and bacterial abundance (dose),
      both on the proportion of Salmonella-positive droplets and the CFU shed per
      droplet (CFU/droplet). In the low-dose treatment, males excreted a greater
      proportion of positive droplets than females. In the high-dose treatment, males
      excreted more CFU/droplet than females. High-dose male flies excreted more
      CFU/droplet than low-dose males, but low-dose females excreted more CFU/droplet
      than high-dose females. Irrespective of sex, low-dose flies excreted a greater
      dose-adjusted CFU (CFU droplet/CFU fed) than high-dose flies. This study
      demonstrates that both bacterial abundance and fly sex may influence excretion of
      bacteria from flies, and should be considered when assessing the risk of house
      fly transmission of pathogens.

PMID- 29659931
TI  - Shade compromises the photosynthetic efficiency of NADP-ME less than that of PEP
      CK and NAD-ME C4 grasses.
AB  - The high energy cost and apparently low plasticity of C4 photosynthesis compared
      with C3 photosynthesis may limit the productivity and distribution of C4 plants
      in low light (LL) environments. C4 photosynthesis evolved numerous times, but it
      remains unclear how different biochemical subtypes perform under LL. We grew
      eight C4 grasses belonging to three biochemical subtypes [NADP-malic enzyme (NADP
      ME), NAD-malic enzyme (NAD-ME), and phosphoenolpyruvate carboxykinase (PEP-CK)]
      under shade (16% sunlight) or control (full sunlight) conditions and measured
      their photosynthetic characteristics at both low and high light. We show for the
      first time that LL (during measurement or growth) compromised the CO2
      concentrating mechanism (CCM) to a greater extent in NAD-ME than in PEP-CK or
      NADP-ME C4 grasses by virtue of a greater increase in carbon isotope
      discrimination (?P) and bundle sheath CO2 leakiness (phi), and a greater
      reduction in photosynthetic quantum yield (Phimax). These responses were partly
      explained by changes in the ratios of phosphoenolpyruvate carboxylase
      (PEPC)/initial Rubisco activity and dark respiration/photosynthesis (Rd/A). Shade
      induced a greater photosynthetic acclimation in NAD-ME than in NADP-ME and PEP-CK
      species due to a greater Rubisco deactivation. Shade also reduced plant dry mass
      to a greater extent in NAD-ME and PEP-CK relative to NADP-ME grasses. In
      conclusion, LL compromised the co-ordination of the C4 and C3 cycles and, hence,
      the efficiency of the CCM to a greater extent in NAD-ME than in PEP-CK species,
      while CCM efficiency was less impacted by LL in NADP-ME species. Consequently,
      NADP-ME species are more efficient at LL, which could explain their agronomic and
      ecological dominance relative to other C4 grasses.

PMID- 29659934
TI  - A New Species of Sucking Louse (Phthiraptera: Anoplura: Polyplacidae) From the
      Gray Mouse Lemur, Microcebus murinus (Primates: Cheirogaleidae), in Madagascar.
AB  - Lemurpediculus madagascariensis sp. nov. (Phthiraptera: Anoplura: Polyplacidae)
      is described from the Gray Mouse lemur, Microcebus murinus (J. F. Miller)
      (Primates: Cheirogaleidae), from Ankarafantsika National Park, Madagascar. Lemurs
      were trapped using Sherman Live Traps and visually inspected for lice, which were
      preserved in 90% ethanol. Adults of both sexes and the third-instar nymph of the
      new species are illustrated and distinguished from the four previously known
      species of Lemurpediculus: L. verruculosus (Ward); L. petterorum Paulian; L.
      claytoni Durden, Blanco, and Seabolt; and L. robbinsi Durden, Blanco, and
      Seabolt. It is not known if the new species of louse is a vector of any pathogens
      or parasites.

PMID- 29659933
TI  - Circulating Tumor Cells in Breast Cancer Patients Treated by Neoadjuvant
      Chemotherapy: A Meta-analysis.
AB  - Background: We conducted a meta-analysis in nonmetastatic breast cancer patients
      treated by neoadjuvant chemotherapy (NCT) to assess the clinical validity of
      circulating tumor cell (CTC) detection as a prognostic marker. Methods: We
      collected individual patient data from 21 studies in which CTC detection by
      CellSearch was performed in early breast cancer patients treated with NCT. The
      primary end point was overall survival, analyzed according to CTC detection,
      using Cox regression models stratified by study. Secondary end points included
      distant disease-free survival, locoregional relapse-free interval, and
      pathological complete response. All statistical tests were two-sided. Results:
      Data from patients were collected before NCT (n = 1574) and before surgery (n =
      1200). CTC detection revealed one or more CTCs in 25.2% of patients before NCT;
      this was associated with tumor size (P < .001). The number of CTCs detected had a
      detrimental and decremental impact on overall survival (P < .001), distant
      disease-free survival (P < .001), and locoregional relapse-free interval (P <
      .001), but not on pathological complete response. Patients with one, two, three
      to four, and five or more CTCs before NCT displayed hazard ratios of death of
      1.09 (95% confidence interval [CI] = 0.65 to 1.69), 2.63 (95% CI = 1.42 to 4.54),
      3.83 (95% CI = 2.08 to 6.66), and 6.25 (95% CI = 4.34 to 9.09), respectively. In
      861 patients with full data available, adding CTC detection before NCT increased
      the prognostic ability of multivariable prognostic models for overall survival (P
      < .001), distant disease-free survival (P < .001), and locoregional relapse-free
      interval (P = .008). Conclusions: CTC count is an independent and quantitative
      prognostic factor in early breast cancer patients treated by NCT. It complements
      current prognostic models based on tumor characteristics and response to therapy.

PMID- 29659935
TI  - Importance of Leishmania Species and Vector Sand Fly (Diptera: Psychodidae)
      Identification.

PMID- 29659936
TI  - Longitudinal Seroprevalence Study Elucidates High Norovirus Burden in Sub-Saharan
      Africa.

PMID- 29659937
TI  - Pioneer Paper: An Accidental Scientist: Chance, Failure, Risk-Taking, and
      Mentoring.
AB  - I never intended to become a scientist. My career developed on the basis of
      chance happenings, repeated failure, the willingness to take risks and the
      acceptance and provision of mentoring. My career has included periods of
      difficulty and shifted back and forth between academic health centers and
      universities in Canada. Although I have been amply recognized for my successes,
      my greatest learning has come from my failures. My greatest satisfaction has been
      in the development, evaluation and dissemination of interventions. The
      combination of intellectual stimulation and emotional gratification has meant a
      rewarding career.

PMID- 29659938
TI  - Mutual Risks of Cutaneous Melanoma and Specific Lymphoid Neoplasms: Second Cancer
      Occurrence and Survival.
AB  - Background: It is unclear whether the established association between cutaneous
      melanoma (CM) and lymphoid neoplasms (LNs) differs across LN subtypes. This study
      quantifies risk for developing CM after specific LNs and, conversely, for
      developing specific LNs after CM, as well as assessing clinical impact. Methods:
      We identified a cohort of Caucasian adults (age 20-83 years) initially diagnosed
      with CM or LN, as reported to 17 US population-based cancer registries, 2000
      2014. Standardized incidence ratios (SIRs) quantified second cancer risk. We
      assessed impact of second cancer development on risk of all-cause mortality using
      Cox regression. Results: Among 151 949 one-or-more-year survivors of first
      primary LN, second primary CM risk was statistically significantly elevated after
      chronic lymphocytic leukemia/small lymphocytic lymphoma (SIR = 1.96, 95%
      confidence interval [CI] = 1.74 to 2.21), follicular lymphoma (SIR = 1.32, 95% CI
      = 1.09 to 1.58), and plasma cell neoplasms (SIR = 1.33, 95% CI = 1.07 to 1.63).
      Risks for these same subtypes were statistically significantly elevated among 148
      336 survivors of first primary CM (SIR = 1.44, 95% CI = 1.25 to 1.66; SIR = 1.47,
      95% CI = 1.21 to 1.77; SIR = 1.25, 95% CI = 1.06 to 1.47; respectively). Risk for
      CM was statistically significantly elevated after diffuse large B-cell lymphoma
      (SIR = 1.22, 95% CI = 1.02 to 1.45) and Hodgkin lymphoma (SIR = 1.75, 95% CI =
      1.33 to 2.26), but the reciprocal relationship was not observed. There were no
      statistically significant associations between marginal zone lymphoma and CM.
      Among survivors of most LN subtypes, CM statistically significantly increased
      risk of death (hazard ratio [HR] range = 1.52, 95% CI = 1.25 to 1.85, to 2.46,
      95% CI = 1.45 to 4.16). Among survivors of CM, LN statistically significantly
      increased risk of death (HR range = 1.75, 95% CI = 1.15 to 2.65, to 6.28, 95% CI
      = 5.00 to 7.88), with the highest risks observed for the most aggressive LN
      subtypes. Conclusions: Heterogeneous associations between CM and specific LN
      subtypes provide novel insights into the etiology of these malignancies, with the
      mutual association between CM and certain LN suggesting shared etiology.
      Development of second primary CM or LN substantially reduces overall survival.

PMID- 29659939
TI  - Persistence of Zika Virus After Birth.

PMID- 29659940
TI  - Risk factors for pericardial effusion after chemoradiotherapy for thoracic
      esophageal cancer-comparison of four-field technique and traditional two opposed
      fields technique.
AB  - Pericardial effusion is an important late toxicity after concurrent
      chemoradiotherapy (CCRT) for locally advanced esophageal cancer. We investigated
      the clinical and dosimetric factors that were related to pericardial effusion
      among patients with thoracic esophageal cancer who were treated with definitive
      CCRT using the two opposed fields technique (TFT) or the four-field technique
      (FFT), as well as the effectiveness of FFT. During 2007-2015, 169 patients with
      middle and/or lower thoracic esophageal cancer received definitive CCRT, and 94
      patients were evaluable (51 FFT cases and 43 TFT cases). Pericardial effusion was
      observed in 74 patients (79%) and appeared at 1-18.5 months (median: 5.25 months)
      after CCRT. The 1-year incidences of pericardial effusions were 73.2% and 76.7%
      in the FFT and TFT groups, respectively (P = 0.6395). The mean doses to the
      pericardium were 28.6 Gy and 31.8 Gy in the FFT and TFT groups, respectively (P =
      0.0259), and the V40 Gy proportions were 33.5% and 48.2% in the FFT and TFT
      groups, respectively (P < 0.0001). Grade 3 pericardial effusion was not observed
      in patients with a pericardial V40 Gy of <40%, or in patients who were treated
      using the FFT. Although the mean pericardial dose and V40 Gy in the FFT group
      were smaller than those in the TFT group, the incidences of pericardial effusion
      after CCRT were similar in both groups. As symptomatic pericardial effusion was
      not observed in patients with a pericardial V40 Gy of <40% or in the FFT group,
      it appears that FFT with a V40 Gy of <40% could help minimize symptomatic
      pericardial effusion.

PMID- 29659941
TI  - Circulating Tumor Cells in Patients Receiving Neoadjuvant Chemotherapy: Refining
      the Paradigm of Prognosis and Treatment Individualization.

PMID- 29659942
TI  - Evolutionary Associations of Endosymbiotic Ciliates Shed Light on the Timing of
      the Marsupial-Placental Split.
AB  - Trichostome ciliates are among the most conspicuous protists in the
      gastrointestinal tract of a large variety of vertebrates. However, little is
      still known about phylogeny of the trichostome/vertebrate symbiotic systems,
      evolutionary correlations between trichostome extrinsic traits, and character
      dependent diversification of trichostomes. These issues were investigated here,
      using the relaxed molecular clock technique along with stochastic mapping of
      character evolution, and binary-state speciation and extinction models. Clock
      analyses revealed that trichostomes colonized the vertebrate gastrointestinal
      tract ~135 Ma, that is, near the paleontological minimum for the split of therian
      mammals into marsupials and placentals. According to stochastic mapping, the last
      common ancestor of trichostomes most likely invaded the hindgut of a mammal.
      Although multiple shifts to fish/amphibian or avian hosts and to the foregut
      compartments took place during the trichostome phylogeny, only transition to the
      foregut was recognized as a key innovation responsible for the explosive
      radiation of ophryoscolecid trichostomes after the Cretaceous/Tertiary boundary,
      when ungulates began their diversification. Since crown radiations of main
      trichostome lineages follow those of their mammalian hosts and are in agreement
      with their historic dispersal routes, the present time-calibrated phylogeny might
      help to elucidate controversies in the geological and molecular timing of the
      split between marsupials and placental mammals.

PMID- 29659944
TI  - Factors Related to Aedes aegypti (Diptera: Culicidae) Populations and Temperature
      Determine Differences on Life-History Traits With Regional Implications in
      Disease Transmission.
AB  - Aedes aegypti (L.) (Diptera: Culicidae) is a vector of many medically significant
      viruses in the Americas, including dengue virus, chikungunya virus, and Zika
      virus. Traits such as longevity, fecundity, and feeding behavior contribute to
      the ability of Ae. aegypti to serve as a vector of these pathogens. Both local
      environmental factors and population genetics could contribute to variability in
      these traits. We performed a comparative study of Ae. aegypti populations from
      four geographically and environmentally distinct collection sites in Argentina in
      which the cohorts from each population were held at temperature values simulating
      a daily cycle, with an average of 25 degrees C in order to identify the influence
      of population on life-history traits. In addition, we performed the study of the
      same populations held at a daily temperature cycle similar to that of the
      surveyed areas. According to the results, Aguaray is the most outstanding
      population, showing features that are important to achieve high fitness. Whereas
      La Plata gathers features consistent with low fitness. Iguazu was outstanding in
      blood-feeding rate while Posadas's population showed intermediate values. Our
      results also demonstrate that climate change could differentially affect unique
      populations, and that these differences have implications for the capacity for
      Ae. aegypti to act as vectors for medically important arboviruses.

PMID- 29659943
TI  - Cooperation process between a local government and experts in official voluntary
      decontamination of environmental radioactivity.
AB  - Kashiwa city, inside the Tokyo metropolitan area and located ~200 km south of the
      Fukushima Dai-ichi Nuclear Power Plant, received a raised environmental ambient
      radiation dose due to the disaster relative to the rest of area. In this paper,
      the challenging process of the official voluntary decontamination activity in
      Kashiwa city, Chiba prefecture, which was carried out with strong cooperation
      between a local government and experts, is described and reviewed in terms of the
      effectiveness of the radiation protection. The support system for the official
      voluntary decontamination work was constructed by the citizens. It was completed
      within ~15 months after the accident, by way of the following five main steps.
      (i) A local forum was organized, commencing an open discussion. (ii) (a) Some
      civic groups started their own activities independent of the national and local
      governments' policies and measures, and (b) Kashiwa city office held information
      symposia and risk communication meetings with key persons as a kind of
      stakeholders as well as education and training of official leaders for voluntary
      decontamination work. (iii) Joint positive discussion and work projects between
      civic groups and the local government were started by key personnel. (iv) Local
      government planned and fixed its official decontamination strategy based on the
      results of several open discussions. (v) A guidance book for official voluntary
      decontamination by citizens was distributed by Kashiwa city office. The
      systematic framework for voluntary decontamination by citizens in Kashiwa city
      was developed through cooperation between a local government and decontamination
      experts, which was rare at that time. The authors believe that the process is
      valuable and should be shared with experts from various fields around the world.

PMID- 29659946
TI  - Ethylene responsive factor ERF110 mediates ethylene-regulated transcription of a
      sex determination-related orthologous gene in two Cucumis species.
AB  - In plants, unisexual flowers derived from developmental sex determination form
      separate stamens and pistils that facilitate cross pollination. In cucumber and
      melon, ethylene plays a key role in sex determination. Six sex determination
      related genes have been identified in ethylene biosynthesis in these Cucumis
      species. The interactions among these genes are thought to involve ethylene
      signaling; however, the underlying mechanism of regulation remains unknown. In
      this study, hormone treatment and qPCR assays were used to confirm expression of
      these sex determination-related genes in cucumber and melon is ethylene
      sensitive. RNA-Seq analysis subsequently helped identify the ethylene responsive
      factor (ERF) gene, CsERF110, related to ethylene signaling and sex determination.
      CsERF110 and its melon ortholog, CmERF110, shared a conserved AP2/ERF domain and
      showed ethylene-sensitive expression. Yeast one-hybrid and ChIP-PCR assays
      further indicated that CsERF110 bound to at least two sites in the promoter
      fragment of CsACS11, while transient transformation analysis showed that CsERF110
      and CmERF110 enhance CsACS11 and CmACS11 promoter activity, respectively. Taken
      together, these findings suggest that CsERF110 and CmERF110 respond to ethylene
      signaling, mediating ethylene-regulated transcription of CsACS11 and CmACS11 in
      cucumber and melon, respectively. Furthermore, the mechanism involved in its
      regulation is thought to be conserved in these two Cucumis species.

PMID- 29659945
TI  - Plasmodium falciparum Falcipain-2a Polymorphisms in Southeast Asia and Their
      Association With Artemisinin Resistance.
AB  - Background: Falcipain-2a ([FP2a] PF3D7_1115700) is a Plasmodium falciparum
      cysteine protease and hemoglobinase. Functional FP2a is required for potent
      activity of artemisinin, and in vitro selection for artemisinin resistance
      selected for an FP2a nonsense mutation. Methods: To investigate associations
      between FP2a polymorphisms and artemisinin resistance and to characterize the
      diversity of the enzyme in parasites from the China-Myanmar border, we sequenced
      the full-length FP2a gene in 140 P falciparum isolates collected during 2004
      2011. Results: The isolates were grouped into 8 different haplotype groups.
      Haplotype group I appeared in samples obtained after 2008, coinciding with
      implementation of artemisinin-based combination therapy in this region. In
      functional studies, compared with wild-type parasites, the FP2a haplotypes
      demonstrated increased ring survival, and all haplotype groups exhibited
      significantly reduced FP2a activity, with group I showing the slowest protease
      kinetics and reduced parasite fitness. Conclusions: These results suggest that
      altered hemoglobin digestion due to FP2a mutations may contribute to artemisinin
      resistance.

PMID- 29659947
TI  - Pediatric Thoracic Trauma in Iraq and Afghanistan.
AB  - Introduction: The objective of this study is to review available data on
      pediatric thoracic trauma seen at U.S. military treatment facilities in Iraq and
      Afghanistan and describe the scope of injuries, patterns seen, and associated
      mortality. The results were compared with adults injured in Iraq and Afghanistan
      and other reports of pediatric thoracic trauma in the literature. Materials and
      Methods: The investigators received approval from the Uniformed Services
      University of the Health Sciences' institutional review board before the study.
      The Joint Theatre Trauma Registry was queried for all patients with an ICD-9 code
      for thoracic trauma. Two-tailed Student's t-test, Mann-Whitney rank sum, chi2,
      ANOVA, or multiple logistic regression was used as indicated. Results: There were
      955 patients under the age of 18 yr, just over 12% of all thoracic trauma.
      Penetrating injuries were common (73.6%), including gunshot wounds. The most
      common pediatric diagnoses were contusions (45%), pneumothorax (40%), and rib
      and/or sternal fractures (18%). The overall mortality for children was 15.2%
      compared with 13.8% and 9% for civilian adults and Coalition members with
      thoracic trauma, respectively. Mortality was inversely related to age among
      pediatric patients. Children under 2 yr of age had the highest mortality (25.1%).
      Patients under 12 yr of age were more likely to die than those between 12 and 18
      (OR 2.02, 95% CI 1.27-3.22) yr. Thoracic vascular injuries and cardiac injuries
      resulted in the highest mortality among pediatric patients. The presence of a
      hemothorax was independently associated with an increased risk for mortality (OR
      1.78, 95% CI 1.06-2.99) as was a concomitant head injury (OR 2.17, 95% CI 1.33
      3.54). There was a 2.7% incidence of burns among pediatric patients with a high
      associated mortality (46.2%). Nearly one-half of all the children identified
      required a transfusion (47%). Conclusion: Penetrating injuries predominated and
      these children commonly required a transfusion. Mortality was inversely related
      to age. Children with a hemothorax or a concomitant head injury had significant
      increases in mortality. Children with thoracic injury as the result of a burn
      suffered the highest mortality.

PMID- 29659949
TI  - EMC10 governs male fertility via maintaining sperm ion balance.
AB  - Infertility is a severe public health problem worldwide that prevails up to 15%
      in reproductive-age couples, and male infertility accounts for half of total
      infertility. Studies on genetically modified animal models have identified lots
      of genes involved in the pathogenesis of male infertility. The underlying causes,
      however, remain largely unclear. In this study, we provide evidence that EMC10,
      one subunit of endoplasmic reticulum (ER) membrane protein complex (EMC), is
      required for male fertility. EMC10 is significantly decreased in spermatozoa from
      patients with asthenozoospermia and positively associated with human sperm
      motility. Male mice lacking Emc10 gene are completely sterile. Emc10-null
      spermatozoa exhibit multiple defects including abnormal morphology, decreased
      motility, impaired capacitation, and impotency of acrosome reaction, thereby
      which are incapable of fertilizing intact or ZP-free oocytes. However, intra
      cytoplasmic sperm injection (ICSI) could rescue this defect caused by EMC10
      deletion. Mechanistically, EMC10 deficiency leads to inactivation of Na/K-ATPase,
      in turn giving rise to an increased level of intracellular Na+ in spermatozoa,
      which contributes to decreased sperm motility and abnormal morphology. Other
      mechanistic investigations demonstrate that the absence of EMC10 results in a
      reduction of HCO3- entry and subsequent decreases of both cAMP-dependent protein
      kinase A (PKA) substrate phosphorylation and protein tyrosine phosphorylation.
      These data demonstrate that EMC10 is indispensable to male fertility via
      maintaining sperm ion balance of Na+ and HCO3-, and also suggest that EMC10 is a
      promising biomarker for male fertility and a potential pharmaceutical target to
      treat male infertility.

PMID- 29659948
TI  - miR156-SPL modules regulate induction of somatic embryogenesis in citrus callus.
AB  - miR156 is a highly conserved plant miRNA and has been extensively studied because
      of its versatile roles in plant development. Here, we report a novel role of
      miR156 in regulating somatic embryogenesis (SE) in citrus, one of the most widely
      cultivated fruit crops in the world. SE is an important means of in vitro
      regeneration, but over the course of long-term sub-culturing there is always a
      decline in the SE potential of the preserved citrus embryogenic callus, and this
      represents a key obstacle for citrus biotechnology. In this study, the SE
      competence of citrus callus of wild kumquat (Fortunella hindsii) was
      significantly enhanced by either overexpression of csi-miR156a or by individual
      knock-down of the two target genes, CsSPL3 and CsSPL14, indicating that the
      effect of miR156-SPL modules was established during the initial phases of SE
      induction. Biological processes that might promote SE in response to miR156
      overexpression were explored using RNA-seq, and mainly included hormone signaling
      pathways, stress responses, DNA methylation, and the cell cycle. CsAKIN10 was
      identified as interacting protein of CsSPL14. Our results provide insights into
      the regulatory pathway through which miR156-SPL modules enhance the SE potential
      of citrus callus, and provide a theoretical basis for improvement of plant SE
      competence.

PMID- 29659950
TI  - Vitamin D3, 25-Hydroxyvitamin D3, and Food Fortification.

PMID- 29659951
TI  - l-Glutamine Attenuates Apoptosis in Porcine Enterocytes by Regulating Glutathione
      Related Redox Homeostasis.
AB  - Background: Programmed cell death plays a fundamental role in intestinal
      development and mucosal homeostasis. Dysregulation of these processes is
      associated with an impaired intestinal-mucosal barrier, reduced nutrient
      absorption, and initiation and progression of intestinal diseases. 4-Hydroxy-2
      nonenal (4-HNE), a product of lipid peroxidation, is commonly used to induce
      oxidative stress in cells. l-Glutamine is known to protect cells from apoptosis.
      However, the underlying mechanisms are largely unknown. Objective: This study was
      conducted to test the hypothesis that l-glutamine attenuates 4-HNE-induced
      apoptosis by modulating glutathione (GSH) and thioredoxin (TXN) antioxidant
      systems and the expression of genes involved in 4-HNE metabolism in enterocytes.
      Methods: Intestinal porcine epithelial cell line 1 (IPEC-1) cells were cultured
      with or without 4-HNE (30 MUmol/L) in the presence of 0.05 or 0.25 mmol l
      glutamine/L (a physiological concentration in the lumen of the small intestine)
      for indicated time periods. Cell viability, abundances of apoptotic proteins,
      mitochondrial membrane depolarization, production of reactive oxygen species
      (ROS) and GSH, and expression of genes involved in the biosynthesis of GSH,
      thioredoxin, and 4-HNE metabolism were determined. Results: Compared with basal
      medium containing 0.05 mmol l-glutamine/L, 4-HNE enhanced apoptosis by 19.6% (P <
      0.05) in a caspase-3-dependent manner. This effect was accompanied by elevated
      intracellular ROS production (39.5% and 85.3% for 2- and 4-h treatment,
      respectively), increased mitochondrial depolarization by 80%, and decreased
      intracellular GSH concentrations by 17.7%. These effects of 4-HNE were reduced by
      0.25 mmol l-glutamine/L. Further study showed that the protective effect of l
      glutamine was associated with the enhanced expression of genes involved in GSH
      production (including GCLC, GCLM, GSR, CBS, and CTH) by 3.9-14-fold, as well as
      genes involved in 4-HNE metabolism [e.g., glutathione S-transferase A (GSTA)1 and
      GSTA4] by 1.9-7.2-fold. The mRNA levels for ADH5, AKR1C1, AKR1A1, and TXNRD1 were
      enhanced 1.4-8.8-fold by 4-HNE but were not changed in cells co-treated with 4
      HNE and l-glutamine. Conclusion: These findings indicate that l-glutamine
      attenuates 4-HNE-induced apoptosis by regulating GSH-related redox homeostasis
      and enhancing GSTA-mediated metabolism in enterocytes.

PMID- 29659952
TI  - ABO Genotype Does Not Modify the Association between the "Blood-Type" Diet and
      Biomarkers of Cardiometabolic Disease in Overweight Adults.
AB  - Background: Although 7 million copies of Eat Right 4 Your Type have been sold in
      >60 languages, there has been a lack of evidence supporting the "blood-type" diet
      hypothesis. Objective: The present study aimed to examine the validity of this
      diet in overweight adults. Methods: A total of 973 adults [mean +/- SEM age: 44.6
      +/- 0.4 y; mean +/- SEM body mass index (BMI; kg/m2): 32.5 +/- 0.2; 758 women,
      215 men] were participants of the Toronto Healthy Diet Study. A 1-mo, 196-item
      food-frequency questionnaire was used to determine dietary intakes before and
      after a 6-mo dietary intervention. Diet scores were calculated to determine
      relative adherence to each of the 4 blood-type diets as a secondary analysis. ABO
      blood group was determined by genotyping rs8176719 and rs8176746. ANCOVA was used
      to compare cardiometabolic risk factors across tertiles of diet scores. Results:
      At baseline, individuals with a higher adherence score to the type A diet had
      lower diastolic blood pressure (tertile 3 compared with tertile 1: 70.9 +/- 1.1
      compared with 73.3 +/- 1.1 mm Hg; P < 0.01). Lower waist circumference was
      observed in individuals with higher adherence to the type B (tertile 3 compared
      with tertile 1: 100.8 +/- 1.8 compared with 105.4 +/- 1.7 cm; P < 0.01) and type
      AB (tertile 3 compared with tertile 1: 101.2 +/- 1.8 compared with 104.8 +/- 1.7
      cm; P < 0.01) diets. After a 6-mo dietary intervention, individuals with
      increased adherence to the type A and type B diets had greater reductions in BMI
      and waist circumference, respectively (P < 0.01). Individuals with an increase in
      type O diet adherence showed decreases in both BMI and waist circumference (P <
      0.01). However, matching the diets with the corresponding ABO genotype of each
      individual did not change the effect size of any of these associations either at
      baseline or at 6 mo. Conclusions: ABO genotype does not modify any association
      between blood-type diets and biomarkers of cardiometabolic disease in overweight
      adults, suggesting that the theory behind this diet is not valid This study was
      based on the data of a trial that was registered at www.clinicaltrials.gov as
      NCT00516620.

PMID- 29659953
TI  - Test-Retest Reproducibility of Adult-Reported High School Diet Varies among
      Racially and Ethnically Diverse US Men and Women.
AB  - Background: Adolescent diet is thought to play an important role in future
      chronic disease risk. However, few studies have examined the reproducibility of
      adult-reported adolescent diet, and evidence for possible differences in
      reproducibility by demographic characteristics is limited. Objective: We assessed
      the ability of adults to consistently report past high school diet over a 1-y
      period and examined differences in reproducibility by selected demographic
      characteristics. Methods: By using age-adjusted partial Spearman (rho) or Pearson
      (r) correlations, we assessed 1-y reproducibility for 33 line items, 20 food
      groups, and 2 dietary patterns of high school diet reported in adulthood via a
      questionnaire completed by 742 participants in the Cancer Prevention Study 3 (CPS
      3) Diet Substudy. Results: Participants' median age was 53 y (range: 31-70 y),
      65.2% were women, 59.8% were non-Hispanic white, 24.8% were non-Hispanic black,
      and 15.4% were Hispanic. The mean Spearman correlation assessing reproducibility
      across the 33 line items was 0.60 and ranged from 0.44 to 0.72, with no
      differences in mean correlations by age, sex, race/ethnicity, education, or body
      mass index (BMI). Reproducibility was similar across food groups (rho = 0.62;
      range: 0.44-0.68), with differences by sex, ethnicity, age, or BMI observed for
      some food groups (e.g., sugar-sweetened beverages). Pearson correlations for the
      reproducibility of 2 major eating patterns, "fast food" and "whole food," were
      0.73 and 0.72, respectively. Conclusion: These results show good 1-y
      reproducibility of assessed high school diet, as reported from memory in
      adulthood, by line item, food group, and dietary pattern, with noted differences
      by demographic characteristics.

PMID- 29659954
TI  - The Ossabaw Pig Is a Suitable Translational Model to Evaluate Dietary Patterns
      and Coronary Artery Disease Risk.
AB  - Background: Animal models that mimic diet-induced human pathogenesis of chronic
      diseases are of increasing importance in preclinical studies. The Ossabaw pig is
      an established model for obesity-related metabolic disorders when fed extreme
      diets in caloric excess. Objective: To increase the translational nature of this
      model, we evaluated the effect of diets resembling 2 human dietary patterns, the
      Western diet (WD) and the Heart Healthy Diet (HHD), without or with atorvastatin
      (-S or +S) therapy, on cardiometabolic risk factors and atherosclerosis
      development. Methods: Ossabaw pigs (n = 32; 16 boars and 16 gilts, aged 5-8 wk)
      were randomized according to a 2 * 2 factorial design into 4 groups (WD-S, WD+S,
      HHD-S, and HHD+S) and were fed the respective diets for 6 mo. The WD (high in
      saturated fat, cholesterol, and refined grain) and the HHD (high in unsaturated
      fat, whole grain, and fruit and vegetables) were isocaloric [38% of energy (%E)
      from fat, 47%E from carbohydrate, and 15%E from protein]. Body composition was
      determined by using dual-energy X-ray absorptiometry, serum fatty acid (FA)
      profiles by gas chromatography, cardiometabolic risk profile by standard
      procedures, and degree of atherosclerosis by histopathology. Results: Serum FA
      profiles reflected the predominant dietary FA. Pigs fed the WD had 1- to 4-fold
      higher concentrations of LDL cholesterol, non-HDL cholesterol, HDL cholesterol,
      high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor alpha (TNF
      alpha), alkaline phosphatase (ALP), and alanine aminotransferase (ALT) compared
      with HHD-fed pigs (all P-diet < 0.05). Statin therapy significantly lowered
      concentrations of LDL cholesterol (-39%), non-HDL cholesterol (-38%), and
      triglycerides (-6%) (P-statin < 0.02). A greater degree of atheromatous changes
      (macrophage infiltration, foam cells, fatty streaks) and lesion incidence was
      documented in the coronary arteries (P-diet < 0.05), as well as 2- to 3-fold
      higher lipid deposition in the aortic arch or thoracic aorta of WD- compared with
      HHD-fed pigs (P-diet < 0.001). Conclusions: Ossabaw pigs manifested a
      dyslipidemic and inflammatory profile accompanied by early-stage atherosclerosis
      when fed a WD compared with an HHD, which was moderately reduced by atorvastatin
      therapy. This phenotype presents a translational model to examine mechanistic
      pathways of whole food-based dietary patterns on atherosclerosis development.

PMID- 29659955
TI  - Accretion of Fat-Free Mass Rather Than Fat Mass in Infancy Is Positively
      Associated with Linear Growth in Childhood.
AB  - Background: We have previously shown that fat-free mass (FFM) at birth is
      associated with height at 2 y of age in Ethiopian children. However, to our
      knowledge, the relation between changes in body composition during early infancy
      and later linear growth has not been studied. Objective: This study examined the
      associations of early infancy fat mass (FM) and FFM accretion with linear growth
      from 1 to 5 y of age in Ethiopian children. Methods: In the infant Anthropometry
      and Body Composition (iABC) study, a prospective cohort study was carried out in
      children in Jimma, Ethiopia, followed from birth to 5 y of age. FM and FFM were
      measured <=6 times from birth to 6 mo by using air-displacement plethysmography.
      Linear mixed-effects models were used to identify associations between
      standardized FM and FFM accretion rates during early infancy and linear growth
      from 1 to 5 y of age. Standardized accretion rates were obtained by dividing FM
      and FFM accretion by their respective SD. Results: FFM accretion from 0 to 6 mo
      of age was positively associated with length at 1 y (beta = 0.64; 95% CI: 0.19,
      1.09; P = 0.005) and linear growth from 1 to 5 y (beta = 0.63; 95% CI: 0.19,
      1.07; P = 0.005). The strongest association with FFM accretion was observed at 1
      y. The association with linear growth from 1 to 5 y was mainly engendered by the
      1-y association. FM accretion from 0 to 4 mo was positively associated with
      linear growth from 1 to 5 y (beta = 0.45; 95% CI: 0.02, 0.88; P = 0.038) in the
      fully adjusted model. Conclusions: In Ethiopian children, FFM accretion was
      associated with linear growth at 1 y and no clear additional longitudinal effect
      from 1 to 5 y was observed. FM accretion showed a weak association from 1 to 5 y.
      This trial was registered at www.controlled-trials.com as ISRCTN46718296.

PMID- 29659956
TI  - Polyphenols Have No Impact on Endothelial Function in Patients with Obstructive
      Sleep Apnea: A Randomized Controlled Trial.
AB  - Background: Endothelial dysfunction, a pathophysiologic determinant of
      atherogenesis, has been found to occur in obstructive sleep apnea syndrome (OSA)
      and is improved by continuous positive airway pressure (CPAP). However, the
      efficacy of CPAP therapy is limited by variable adherence. Alternative treatment
      strategies are needed. The impact of polyphenols on endothelial function has
      never been evaluated in OSA. Objective: We evaluated the impact of 1-mo
      supplementation with grape juice polyphenols (GJPs) on the reactive hyperemia
      index (RHI), a validated measure of endothelial function in patients with severe
      OSA. Methods: Forty participants [75% men, median (IQR) age: 61 y (34, 64 y), BMI
      (in kg/m2): 30.6 (20.9, 33.7)] with severe OSA [median apnea-hypopnea index 43/h
      (33/h, 56/h)] were randomly assigned to receive GJPs (300 mg/d; n = 20) or
      placebo (n = 20) for 1 mo. The primary outcome was the change in RHI between
      baseline and after 1 mo of GJPs or placebo. Secondary outcome measures included
      changes in blood pressure (BP), heart rate (HR), and polysomnographic indexes.
      Results: No significant differences in RHI and BP outcomes were observed between
      the GJPs and placebo groups. A significant between-group difference was observed
      for HR changes [-1 bpm (-5, +5 bpm) in the GJPs group compared with +6 bpm (+3,
      +10 bpm) in the placebo group; P = 0.001]. A significant decrease in total sleep
      time was observed in the GJPs group compared with the placebo group [-10 min (
      33, 6 min) compared with +15 min (-12, 40 min), respectively; P = 0.02], with no
      between-group differences in the distribution of sleep stages. Conclusions: In
      participants with severe OSA and no overt cardiovascular disease, 1-mo GJP
      supplementation had no effect on endothelial function. This trial was registered
      at clinicaltrials.gov as NCT01977924.

PMID- 29659957
TI  - Dietary Fermentable Fibers Attenuate Chronic Kidney Disease in Mice by Protecting
      the Intestinal Barrier.
AB  - Background: Chronic kidney disease (CKD) is a worldwide health problem. Although
      the pathogenesis of CKD is still unclear, recent studies suggest that systemic
      inflammation caused by a dysregulated microflora and an impaired intestinal
      barrier is involved in CKD development. Objective: We investigated the effects of
      the fermentable dietary fibers (DFs), unmodified guar gum (GG), and partially
      hydrolyzed GG (PHGG) (i.e., substances with distinct viscosity characteristics)
      on CKD development, with a particular focus on colonic tight junction (TJ)
      barriers in mice. Methods: Male 7-wk-old ICR mice were fed an AIN-93G diet that
      contained 0.25% adenine for 2 wk to induce CKD. Mice fed adenine were then
      divided into 3 groups and fed the unsupplemented diet (CKD) or a diet containing
      10% PHGG (CKD+PHGG) or GG (CKD+GG) for 3 wk. Control (CON) mice were fed an AIN
      93G diet without adenine throughout the 5-wk experiment. Plasma urea
      concentration; the colonic TJ proteins zonula occludens (ZO) 1, ZO2, occludin,
      junctional adhesion molecule A (JAMA), and claudin isoforms; renal inflammatory
      cytokines tumor necrosis factor alpha (Tnfa), interleukin (Il ) 1beta (Il1b), and
      Il6; and cecal short-chain fatty acids (SCFAs) and microflora were analyzed.
      Results: Compared with the CON, CKD+PHGG, and CKD+GG groups, the CKD group had a
      2.2- to 4.4-fold higher plasma urea concentration and greater expression of
      inflammatory cytokine genes in the kidney, including Tnfa (4.4- to 48-fold), Il1b
      (4.6- to 56-fold), and Il6 (8.8- to 115-fold). The CON, CKD+PHGG, and CKD+GG
      groups had greater expression of colonic TJ proteins including ZO1 (2.9- to 3.7
      fold), ZO2 (3.4- to 4.3-fold), occludin (3.0- to 3.3-fold), JAMA (4.4- to 5.4
      fold), and claudin 7 (2.1- to 2.6-fold) and higher cecal SCFA (1.8- to 3.5-fold)
      and Lactobacillus (2.7- to 4.0-fold) concentrations than the CKD group.
      Conclusion: Supplemental feeding with fermentable DFs, such as GG and PHGG, might
      be effective for the prevention or management of CKD by restoring colonic barrier
      integrity and microflora composition, as shown in mice.

PMID- 29659959
TI  - Reply to TR Hill and I Kyriazakis.

PMID- 29659958
TI  - Food Photography Is Not an Accurate Measure of Energy Intake in Obese, Pregnant
      Women.
AB  - Background: To improve weight management in pregnant women, there is a need to
      deliver specific, data-based recommendations on energy intake. Objective: This
      cross-sectional study evaluated the accuracy of an electronic reporting method to
      measure daily energy intake in pregnant women compared with total daily energy
      expenditure (TDEE). Methods: Twenty-three obese [mean +/- SEM body mass index
      (kg/m2): 36.9 +/- 1.3] pregnant women (aged 28.3 +/-1.1 y) used a smartphone
      application to capture images of their food selection and plate waste in free
      living conditions for >=6 d in early (13-16 wk) and late (35-37 wk) pregnancy.
      Energy intake was evaluated by the smartphone application SmartIntake and
      compared with simultaneous assessment of TDEE obtained by doubly labeled water.
      Accuracy was defined as reported energy intake compared with TDEE (percentage of
      TDEE). Ecological momentary assessment prompts were used to enhance data
      reporting. Two-one-sided t tests for the 2 methods were used to assess
      equivalency, which was considered significant when accuracy was >80%. Results:
      Energy intake reported by the SmartIntake application was 63.4% +/- 2.3% of TDEE
      measured by doubly labeled water (P = 1.00). Energy intake reported as snacks
      accounted for 17% +/- 2% of reported energy intake. Participants who used their
      own phones compared with participants who used borrowed phones captured more
      images (P = 0.04) and had higher accuracy (73% +/- 3% compared with 60% +/- 3% of
      TDEE; P = 0.01). Reported energy intake as snacks was significantly associated
      with the accuracy of SmartIntake (P = 0.03). To improve data quality, excluding
      erroneous days of likely underreporting (<60% TDEE) improved the accuracy of
      SmartIntake, yet this was not equivalent to TDEE (-22% +/- 1% of TDEE; P = 1.00).
      Conclusions: Energy intake in obese, pregnant women obtained with the use of an
      electronic reporting method (SmartIntake) does not accurately estimate energy
      intake compared with doubly labeled water. However, accuracy improves by applying
      criteria to eliminate erroneous data. Further evaluation of electronic reporting
      in this population is needed to improve compliance, specifically for reporting
      frequent intake of small meals. This trial was registered at
      www.clinicaltrials.gov as NCT01954342.

PMID- 29659961
TI  - Multi-Copper Ferroxidase-Deficient Mice Have Increased Brain Iron Concentrations
      and Learning and Memory Deficits.
AB  - Background: The accumulation of iron occurs in the central nervous system (CNS)
      in several neurodegenerative diseases. Although multi-copper ferroxidases (MCFs)
      play an important role in cellular iron metabolism and homeostasis, the mechanism
      of MCFs in the CNS remains unclear. Objective: The aim was to study the role of
      MCFs in CNS iron metabolism and homeostasis by using hephaestin/ceruloplasmin
      (Heph/Cp) double knockout (KO) mice. Methods: Heph/Cp double KO male mice were
      generated by crossing both single KO mice. In Heph/Cp KO and wild-type (WT)
      control mice at 4 wk and 6 mo of age, iron concentrations of selected brain
      regions were measured by atomic absorption spectrophotometry, and gene
      expressions of Heph, Cp, ferroportin 1 (Fpn1) [+ iron responsive element (IRE)],
      L-ferritin, H-ferritin, transferrin receptor 1 (Tfrc), and divalent metal
      transporter 1 (Dmt1) (+IRE) were quantitated by quantitative reverse
      transcriptase-polymerase chain reaction. Brain region L-ferritin protein
      concentration, superoxide dismutase (SOD), and glutathione peroxidase (GPx)
      activities and malondialdehyde (MDA) concentration were also determined. Learning
      and memory abilities in Heph/Cp KO and WT control mice at 6 mo of age were tested
      by the IntelliCage system (New Behavior). Results: Iron concentration was
      significantly higher in Heph/Cp KO mice than in WT control mice at 4 wk of age in
      the cortex (50%), hippocampus (120%), brainstem (35%), and cerebellum (220%) and
      at 6 mo of age in the cortex (140%), hippocampus (420%), brainstem (560%), and
      cerebellum (340%). L-Ferritin and MDA concentrations were significantly higher
      and SOD and GPx activities were significantly lower in the cortex, hippocampus,
      brainstem, and cerebellum of KO mice than in those of WT controls at both 4 wk
      and 6 mo of age. Iron-related gene expressions also differed significantly
      between groups. Learning and memory deficits occurred in Heph/Cp KO mice at 6 mo
      of age. Conclusion: Mutation of both MCFs in mice induces iron accumulation in
      brain regions, oxidative damage, and learning and memory defects.

PMID- 29659960
TI  - Obese Mice Losing Weight Due to trans-10,cis-12 Conjugated Linoleic Acid
      Supplementation or Food Restriction Harbor Distinct Gut Microbiota.
AB  - Background: trans-10,cis-12 Conjugated linoleic acid (t10,c12-CLA) is a dietary
      supplement that promotes weight loss by increasing fat oxidation and energy
      expenditure. We previously reported that in the absence of t10,c12-CLA, mice
      forced to lose equivalent body weight by food restriction (FR) do not exhibit
      increases in fat oxidation or energy expenditure but have improved glucose
      metabolism, consistent with FR as a metabolically healthy weight-loss method.
      Objective: Because diet is a primary determinant of gut bacterial populations, we
      hypothesized that the disparate metabolic effects accompanying weight loss from
      t10,c12-CLA or FR could be related to altered intestinal microbiota. Methods: Ten
      week-old male LDL receptor-deficient (Ldlr-/-) mice were fed a high-fat, high
      sucrose diet (HFHS; 36% lard fat, 36.2% sucrose + 0.15% cholesterol) for 12 wk
      (baseline), then switched to the HFHS diet alone (obese control), HFHS + 1%
      c9,t11-CLA (obese fatty acid control), HFHS + 1% t10,c12-CLA (weight-loss
      inducing fatty acid), or HFHS + FR (weight-loss control group with 75-85% ad
      libitum HFHS food intake) for a further 8 wk. Fecal microbial content, short
      chain fatty acids (butyrate, acetate), tissue CLA concentrations, and intestinal
      nutrient transporter expression were quantified. Results: Mice fed t10,c12-CLA or
      assigned to FR lost 14.5% of baseline body weight. t10,c12-CLA-fed mice had
      elevated concentrations of fecal butyrate (2-fold) and plasma acetate (1.5-fold)
      compared with HFHS-fed controls. Fecal alpha diversity decreased by 7.6-14% in
      all groups. Butyrivibrio and Roseburia, butyrate-producing microbes, were
      enriched over time by t10,c12-CLA. By comparing with each control group, we also
      identified bacterial genera significantly enriched in the t10,c12-CLA recipients,
      including Lactobacillus, Actinobacteria, and the newly identified Ileibacterium
      valens of the Allobaculum genus, whereas other taxa were enriched by FR,
      including Clostridiales and Bacteroides. Conclusion: Modalities resulting in
      equivalent weight loss but with divergent metabolic effects are associated with
      compositional differences in the mouse intestinal microbiota.

PMID- 29659962
TI  - Low Dietary Folate Interacts with MTHFD1 Synthetase Deficiency in Mice, a Model
      for the R653Q Variant, to Increase Incidence of Developmental Delays and Defects.
AB  - Background: Suboptimal folate intake, a risk factor for birth defects, is common
      even in areas with folate fortification. A polymorphism in
      methylenetetrahydrofolate dehydrogenase 1 (MTHFD1), R653Q (MTHFD1 c.1958 G > A),
      has also been associated with increased birth defect risk, likely through reduced
      purine synthesis. Objective: We aimed to determine if the interaction of MTHFD1
      synthetase deficiency and low folate intake increases developmental abnormalities
      in a mouse model for MTHFD1 R653Q. Methods: Female Mthfd1S+/+ and Mthfd1S+/- mice
      were fed control or low-folate diets (2 and 0.3 mg folic acid/kg diet,
      respectively) before mating and during pregnancy. Embryos and placentas were
      examined for anomalies at embryonic day 10.5. Maternal 1-carbon metabolites were
      measured in plasma and liver. Results: Delays and defects doubled in litters of
      Mthfd1S+/- females fed low-folate diets compared to wild-type females fed either
      diet, or Mthfd1S+/- females fed control diets [P values (defects): diet 0.003,
      maternal genotype 0.012, diet * maternal genotype 0.014]. These adverse outcomes
      were associated with placental dysmorphology. Intrauterine growth restriction was
      increased by embryonic Mthfd1S+/- genotype, folate deficiency, and interaction of
      maternal Mthfd1S+/- genotype with folate deficiency (P values: embryonic genotype
      0.045, diet 0.0081, diet * maternal genotype 0.0019). Despite a 50% increase in
      methylenetetrahydrofolate reductase expression in low-folate maternal liver (P
      diet = 0.0007), methyltetrahydrofolate concentration decreased 70% (P diet
      <0.0001) and homocysteine concentration doubled in plasma (P diet = 0.0001); S
      adenosylmethionine decreased 40% and S-adenosylhomocysteine increased 20% in low
      folate maternal liver (P diet = 0.002 and 0.0002, respectively). Conclusions:
      MTHFD1 synthetase-deficient mice are more sensitive to low folate intake than
      wild-type mice during pregnancy. Reduced purine synthesis due to synthetase
      deficiency and altered methylation potential due to low folate may increase
      pregnancy complications. Further studies and individualized intake
      recommendations may be required for women homozygous for the MTHFD1 R653Q
      variant.

PMID- 29659963
TI  - Saturated Fats from Butter but Not from Cheese Increase HDL-Mediated Cholesterol
      Efflux Capacity from J774 Macrophages in Men and Women with Abdominal Obesity.
AB  - Background: Recent evidence suggests that the association between dietary
      saturated fatty acids (SFAs) and coronary artery disease risk varies according to
      food sources. How SFAs from butter and cheese influence HDL-mediated cholesterol
      efflux capacity (CEC), a key process in reverse cholesterol transport, is
      currently unknown. Objective: In a predefined secondary analysis of a previously
      published trial, we have examined how diets rich in SFAs from either cheese or
      butter influence HDL-mediated CEC, compared with diets rich in either
      monounsaturated fatty acids (MUFAs) or polyunsaturated fatty acids (PUFAs).
      Methods: In a randomized crossover controlled consumption trial, 46 men and women
      with abdominal obesity consumed 5 isocaloric diets, each for 4 wk. Two diets were
      rich in SFAs either from cheese (CHEESE) or butter (BUTTER) [12.4-12.6% of energy
      (%E) as SFAs, 32%E as fat, 52%E as carbohydrates]. In 2 other diets, SFAs (5.8%E)
      were replaced with either MUFAs from refined olive oil (MUFA) or PUFAs from corn
      oil (PUFA). Finally, a lower fat and carbohydrate diet was used as a control
      (5.8%E as SFAs, 25.0%E as fat, 59%E as carbohydrates; CHO). Post-diet HDL
      mediated CEC was determined ex vivo using radiolabelled J774 macrophages
      incubated with apolipoprotein B-depleted serum from the participants. Results:
      Mean (+/-SD) age was 41.4 +/- 14.2 y, and waist circumference was 107.6 +/- 11.5
      cm in men and 94.3 +/- 12.4 cm in women. BUTTER and MUFA increased HDL-mediated
      CEC compared with CHEESE (+4.3%, P = 0.026 and +4.7%, P = 0.031, respectively).
      Exploring the significant diet * sex interaction (P = 0.044) revealed that the
      increase in HDL-mediated CEC after BUTTER compared with CHEESE was significant
      among men (+6.0%, P = 0.047) but not women (+2.9%, P = 0.19), whereas the
      increase after MUFA compared with CHEESE was significant among women (+9.1%, P =
      0.008) but not men (-0.6%, P = 0.99). Conclusion: These results provide evidence
      of a food matrix effect modulating the impact of dairy SFAs on HDL-mediated CEC
      with potential sex-related differences that deserve further investigation. This
      trial was registered at clinicaltrials.gov as NCT02106208.

PMID- 29659964
TI  - Universal Salt Iodization Provides Sufficient Dietary Iodine to Achieve Adequate
      Iodine Nutrition during the First 1000 Days: A Cross-Sectional Multicenter Study.
AB  - Background: Dietary iodine requirements are high during pregnancy, lactation, and
      infancy, making women and infants vulnerable to iodine deficiency. Universal salt
      iodization (USI) has been remarkably successful for preventing iodine deficiency
      in the general population, but it is uncertain if USI provides adequate iodine
      intakes during the first 1000 d. Objective: We set out to assess if USI provides
      sufficient dietary iodine to meet the iodine requirements and achieve adequate
      iodine nutrition in all vulnerable population groups. Methods: We conducted an
      international, cross-sectional, multicenter study in 3 study sites with mandatory
      USI legislation. We enrolled 5860 participants from 6 population groups (school
      age children, nonpregnant nonlactating women of reproductive age, pregnant women,
      lactating women, 0-6-mo-old infants, and 7-24-mo-old infants) and assessed iodine
      status [urinary iodine concentration (UIC)] and thyroid function in Linfen, China
      (n = 2408), Tuguegarao, the Philippines (n = 2512), and Zagreb, Croatia (n =
      940). We analyzed the iodine concentration in household salt, breast milk,
      drinking water, and cow's milk. Results: The salt iodine concentration was low
      (<15 mg/kg) in 2.7%, 33.6%, and 3.1%, adequate (15-40 mg/kg) in 96.3%, 48.4%, and
      96.4%, and high (>40 mg/kg) in 1.0%, 18.0%, and 0.5% of household salt samples in
      Linfen (n = 402), Tuguegarao (n = 1003), and Zagreb (n = 195), respectively. The
      median UIC showed adequate iodine nutrition in all population groups, except for
      excessive iodine intake in school-age children in the Philippines and borderline
      low intake in pregnant women in Croatia. Conclusions: Salt iodization at ~25
      mg/kg that covers a high proportion of the total amount of salt consumed supplies
      sufficient dietary iodine to ensure adequate iodine nutrition in all population
      groups, although intakes may be borderline low during pregnancy. Large variations
      in salt iodine concentrations increase the risk for both low and high iodine
      intakes. Strict monitoring of the national salt iodization program is therefore
      essential for optimal iodine nutrition. This trial was registered at
      clinicaltrials.gov as NCT02196337.

PMID- 29659965
TI  - A Healthy Asian A Posteriori Dietary Pattern Correlates with A Priori Dietary
      Patterns and Is Associated with Cardiovascular Disease Risk Factors in a
      Multiethnic Asian Population.
AB  - Background: Healthful dietary patterns are associated with cardiovascular disease
      risk factors in Western populations. However, a consistent healthful dietary
      pattern across major Asian ethnic groups has yet to be identified. Objective: We
      aimed to identify a posteriori dietary patterns for Chinese, Malay, and Indian
      ethnic groups in an urban Asian setting, compare these with a priori dietary
      patterns, and ascertain associations with cardiovascular disease risk factors
      including hypertension, obesity, and abnormal blood lipid concentrations.
      Methods: We used cross-sectional data from 8433 Singapore residents (aged 21-94
      y) from the Multi-Ethnic Cohort study of Chinese, Malay, and Indian ethnicity.
      Food consumption was assessed using a validated 169-item food-frequency
      questionnaire. With the use of 28 food groups, dietary patterns were derived by
      principal component analysis, and their association with cardiovascular disease
      risk factors was assessed using multiple linear regression. Associations between
      derived patterns and a priori patterns (aHEI-2010-Alternative Healthy Eating
      Index-2010, aMED-alternate Mediterranean Diet, and DASH-Dietary Approaches to
      Stop Hypertension) were assessed, and the magnitude of associations with risk
      factors compared. Results: We identified a "healthy" dietary pattern, similar
      across ethnic groups, and characterized by high intakes of whole grains, fruit,
      dairy, vegetables, and unsaturated cooking oil and low intakes of Western fast
      foods, sugar-sweetened beverages, poultry, processed meat, and flavored rice.
      This "healthy" pattern was inversely associated with body mass index (BMI; in
      kg/m2) (-0.26 per 1 SD of the pattern score; 95% CI: -0.36, -0.16), waist
      circumference (-0.57 cm; 95% CI: -0.82, -0.32), total cholesterol (-0.070 mmol/L;
      95% CI: -0.091, -0.048), LDL cholesterol (-0.054 mmol/L; 95% CI: -0.074, -0.035),
      and fasting triglycerides (-0.22 mmol/L; 95% CI: -0.04, -0.004) and directly
      associated with HDL cholesterol (0.013 mmol/L; 95% CI: 0.006, 0.021). Generally,
      "healthy" pattern associations were at least as strong as a priori pattern
      associations with cardiovascular disease risk factors. Conclusion: A healthful
      dietary pattern that correlated well with a priori patterns and was associated
      with lower BMI, serum LDL cholesterol, total cholesterol, and fasting
      triglyceride concentrations was identified across 3 major Asian ethnic groups.

PMID- 29659966
TI  - Peri-Urban, but Not Urban, Residence in Bolivia Is Associated with Higher Odds of
      Co-Occurrence of Overweight and Anemia among Young Children, and of Households
      with an Overweight Woman and Stunted Child.
AB  - Background: Urban populations have grown globally alongside emerging simultaneous
      burdens of undernutrition and obesity. Yet, how heterogeneous urban environments
      are associated with this nutritional double burden is poorly understood.
      Objective: We aimed to determine: 1) the prevalence of the nutritional double
      burden and its components in urban, peri-urban, and rural areas of Bolivia; and
      2) the association of residence in these areas with the nutritional double burden
      and its components. Design: We surveyed 3946 randomly selected households from 2
      metropolitan regions of Bolivia. Census data and remotely sensed imagery were
      used to define urban, peri-urban, and rural districts along a transect in each
      region. We defined 5 nutritional double burdens: concurrent overweight and anemia
      among women of reproductive age (15-49 y), and children (6-59 mo), respectively;
      concurrent overweight and stunting among children; and households with an
      overweight woman and, respectively, an anemic or stunted child. Capillary
      hemoglobin concentrations were measured to assess anemia (women: hemoglobin <120
      g/L; children: hemoglobin <110 g/L), and overweight and stunting were calculated
      from height, weight, and age data. Results: In multiple logistic regression
      models, peri-urban, but not urban residence, was associated with higher odds of
      concurrent overweight and anemia among children (OR: 1.8; 95% CI; 1.0, 3.2) and
      of households with an overweight woman and stunted child (1.8; 1.2, 2.7).
      Examining the components of the double burden, peri-urban women and children,
      respectively, had higher odds of overweight than rural residents [women (1.5;
      1.2, 1.8); children (1.5; 1.0, 2.4)], and children from peri-urban regions had
      higher odds of stunting (1.5; 1.1, 2.2). Conclusions: Peri-urban, but not urban,
      residence in Bolivia is associated with a higher risk of the nutritional double
      burden than rural areas. Understanding how heterogeneous urban environments
      influence nutrition outcomes could inform integrated policies that simultaneously
      address both undernutrition and obesity.

PMID- 29659967
TI  - Carbohydrate Replacement of Rice or Potato with Lentils Reduces the Postprandial
      Glycemic Response in Healthy Adults in an Acute, Randomized, Crossover Trial.
AB  - Background: The postprandial blood glucose response (PBGR) following carbohydrate
      replacement of high-glycemic index (GI) foods with pulses, in a mixed meal, has
      not been accurately defined. Objective: We aimed to determine the extent to which
      PBGR and relative glycemic response (RGR) are lowered when half of the available
      carbohydrate (AC) from rice or potato is replaced with cooked lentils. Methods:
      Using a crossover design, 2 groups of 24 healthy adults randomly consumed 50 g AC
      from control white rice alone [mean +/- SD body mass index (BMI, in kg/m2): 24.3
      +/- 0.5; mean +/- SD age: 27.7 +/- 1.2 y], instant potato alone (BMI: 24.0 +/-
      0.5; age: 27.4 +/- 1.2 y), or the same starch source in a 50:50 AC combination
      with each of 3 types of commercially available lentils (large green, small green,
      split red). Fasting and postprandial blood samples were analyzed for glucose and
      insulin, and used to derive incremental area under the curve (iAUC), RGR, and
      maximum concentration (Cmax). Treatment effects were assessed with the use of
      repeated-measures ANOVA within the rice and potato treatments. Results: In
      comparison to rice alone, blood glucose iAUC and Cmax (P < 0.001) were lowered
      after consumption of rice with large green (P = 0.057), small green (P = 0.002),
      and split red (P = 0.006) lentils. Blood glucose iAUC and Cmax were also
      significantly lowered (P < 0.0001) after consumption of potato combined with each
      lentil, compared to potato alone. Plasma insulin iAUC and Cmax were significantly
      (P < 0.001) decreased when lentils were combined with potato, but not with rice.
      The RGRs of rice and potato were lowered by ~20% and 35%, respectively, when half
      of their AC was replaced with lentils. Conclusions: Replacing half of the AC from
      high-GI foods with lentils significantly attenuates PBGR in healthy adults; this
      can contribute to defining a health claim for pulses and blood glucose lowering.
      This trial was registered at clinicaltrials.gov as NCT02426606.

PMID- 29659968
TI  - Healthy Plant-Based Diets Are Associated with Lower Risk of All-Cause Mortality
      in US Adults.
AB  - Background: Plant-based diets, often referred to as vegetarian diets, are
      associated with health benefits. However, the association with mortality is less
      clear. Objective: We investigated associations between plant-based diet indexes
      and all-cause and cardiovascular disease mortality in a nationally representative
      sample of US adults. Methods: Analyses were based on 11,879 participants (20-80 y
      of age) from NHANES III (1988-1994) linked to data on all-cause and
      cardiovascular disease mortality through 2011. We constructed an overall plant
      based diet index (PDI), which assigns positive scores for plant foods and
      negative scores for animal foods, on the basis of a food-frequency questionnaire
      administered at baseline. We also constructed a healthful PDI (hPDI), in which
      only healthy plant foods received positive scores, and a less-healthful
      (unhealthy) PDI (uPDI), in which only less-healthful plant foods received
      positive scores. Cox proportional hazards models were used to estimate the
      association between plant-based diet consumption in 1988-1994 and subsequent
      mortality. We tested for effect modification by sex. Results: In the overall
      sample, PDI and uPDI were not associated with all-cause or cardiovascular disease
      mortality after controlling for demographic characteristics, socioeconomic
      factors, and health behaviors. However, among those with an hPDI score above the
      median, a 10-unit increase in hPDI was associated with a 5% lower risk in all
      cause mortality in the overall study population (HR: 0.95; 95% CI: 0.91, 0.98)
      and among women (HR: 0.94; 95% CI: 0.88, 0.99), but not among men (HR: 0.95; 95%
      CI: 0.90, 1.01). There was no effect modification by sex (P-interaction > 0.10).
      Conclusions: A nonlinear association between hPDI and all-cause mortality was
      observed. Healthy plant-based diet scores above the median were associated with a
      lower risk of all-cause mortality in US adults. Future research exploring the
      impact of quality of plant-based diets on long-term health outcomes is necessary.

PMID- 29659969
TI  - Aspartame Consumption for 12 Weeks Does Not Affect Glycemia, Appetite, or Body
      Weight of Healthy, Lean Adults in a Randomized Controlled Trial.
AB  - Background: Low-calorie sweeteners are often used to moderate energy intake and
      postprandial glycemia, but some evidence indicates that they may exacerbate these
      aims. Objective: The trial's primary aim was to assess the effect of daily
      aspartame ingestion for 12 wk on glycemia. Effects on appetite and body weight
      were secondary aims. Methods: One hundred lean [body mass index (kg/m2): 18-25]
      adults aged 18-60 y were randomly assigned to consume 0, 350, or 1050 mg
      aspartame/d (ASP groups) in a beverage for 12 wk in a parallel-arm design. At
      baseline, body weight and composition were determined, a 240-min oral-glucose
      tolerance test (OGTT) was administered, and measurements were made of appetite
      and selected hormones. Participants also collected a 24-h urine sample. During
      the intervention, the 0-mg/d ASP group consumed capsules containing 680 mg
      dextrose and 80 mg para-amino benzoic acid. For the 350-mg/d ASP group, the
      beverage contained 350 mg aspartame and the 1050-mg/d ASP group consumed the same
      beverage plus capsules containing 680 mg dextrose and 700 mg aspartame. Body
      weight, blood pressure, heart rate, and waist circumference were measured weekly.
      At weeks 4, 8, and 12, participants collected 24-h urine samples and kept
      appetite logs. Baseline measurements were repeated at week 12. Results: With the
      exception of the baseline OGTT glucose concentration at 60 min (and resulting
      area under the curve value), there were no group differences for glucose,
      insulin, resting leptin, glucagon-like peptide 1, or gastric inhibitory peptide
      at baseline or week 12. There also were no effects of aspartame ingestion on
      appetite, body weight, or body composition. Compliance with the beverage
      intervention was ~95%. Conclusions: Aspartame ingested at 2 doses for 12 wk had
      no effect on glycemia, appetite, or body weight among healthy, lean adults. These
      data do not support the view that aspartame is problematic for the management of
      glycemia, appetite, or body weight. This trial was registered at
      www.clinicaltrials.gov as NCT02999321.

PMID- 29659970
TI  - Cholic Acid Supplementation of a High-Fat Obesogenic Diet Suppresses Hepatic
      Triacylglycerol Accumulation in Mice via a Fibroblast Growth Factor 21-Dependent
      Mechanism.
AB  - Background: Supplementation of a high-fat obesogenic diet (HFD) with cholic acid
      (CA) suppresses the development of obesity, insulin resistance, and hepatic
      steatosis in mice. Objective: We investigated the role of fibroblast growth
      factor 21 (FGF21) in mediating the beneficial actions of CA on metabolic
      syndrome. Methods: Male 7-wk-old wild-type (WT) mice and FGF21 knockout (FGF21KO)
      mice were fed an HFD for 12 wk followed by a 4-wk period in which the mice were
      fed the HFD alone or supplemented with 0.5% CA. Body composition, gross energy
      efficiency, glucose tolerance, homeostasis model assessment of insulin resistance
      (HOMA-IR), and hepatic triacylglycerol (TG) concentrations were measured.
      Results: CA administration improved glucose tolerance and decreased total body
      fat accretion, gross energy efficiency, fasting blood glucose concentrations, and
      HOMA-IR in both WT mice and FGF21KO mice. The extent of the effect of CA on
      glucose tolerance, fasting blood glucose concentrations, and HOMA-IR was similar
      in both mouse strains, whereas the extent of the effect of CA on total body fat
      accretion and gross energy efficiency was 4.2- to 4.4-fold greater in FGF21KO
      mice than in WT mice. Further analyses showed that CA decreased hepatic TG
      concentrations in WT mice (49%) but had no effect on hepatic TG concentrations in
      FGF21KO mice. CA decreased the activation state of hepatic acetyl-CoA carboxylase
      1 (ACC1) and adipose tissue hormone-sensitive lipase (HSL) in WT mice but was not
      effective in decreasing the activation of ACC1 and HSL in FGF21KO mice.
      Conclusions: FGF21 signaling is required for the beneficial effect of CA on
      hepatic TG accumulation in mice fed an HFD. We propose that FGF21 signaling
      potentiates the ability of CA to decrease the activation of ACC1 and HSL, key
      enzymes controlling the supply of long-chain fatty acid precursors for hepatic TG
      synthesis.

PMID- 29659971
TI  - New Insight about Height: Body-Composition Changes in Infancy Predict Later
      Linear Growth.

PMID- 29659972
TI  - Acceleration of Olfactory Receptor Gene Loss in Primate Evolution: Possible Link
      to Anatomical Change in Sensory Systems and Dietary Transition.
AB  - Primates have traditionally been regarded as vision-oriented animals with low
      olfactory ability, though this "microsmatic primates" view has been challenged
      recently. To clarify when and how degeneration of the olfactory system occurred
      and to specify the relevant factors during primate evolution, we here examined
      the olfactory receptor (OR) genes from 24 phylogenetically and ecologically
      diverse primate species. The results revealed that strepsirrhines with curved
      noses had functional OR gene repertoires that were nearly twice as large as those
      for haplorhines with simple noses. Neither activity pattern (nocturnal/diurnal)
      nor color vision system showed significant correlation with the number of
      functional OR genes while phylogeny and nose structure (haplorhine/strepsirrhine)
      are statistically controlled, but extent of folivory did. We traced the
      evolutionary fates of individual OR genes by identifying orthologous gene groups,
      demonstrating that the rates of OR gene losses were accelerated at the ancestral
      branch of haplorhines, which coincided with the acquisition of acute vision. The
      highest rate of OR gene loss was observed at the ancestral branch of leaf-eating
      colobines; this reduction is possibly linked with the dietary transition from
      frugivory to folivory because odor information is essential for fruit foraging
      but less so for leaf foraging. Intriguingly, we found accelerations of OR gene
      losses in an external branch to every hominoid species examined. These findings
      suggest that the current OR gene repertoire in each species has been shaped by a
      complex interplay of phylogeny, anatomy, and habitat; therefore, multiple factors
      may contribute to the olfactory degeneration in primates.

PMID- 29659973
TI  - The Diagnostic Challenge of Acquired Thrombotic Thrombocytopenic Purpura in
      Children: Case Report and Review of the Literature.
AB  - Acquired thrombotic thrombocytopenic purpura (TTP) is a rare disease in children.
      Despite advances in diagnosis and treatment, acquired TTP remains a challenging
      disease due to the lack of a simple diagnostic test and the variable response to
      plasma exchange. Herein, we describe a case of a 5-year-old of black ethnicity
      boy who presented with a sudden onset of fatigue and body aches. Laboratory
      investigations revealed a thrombotic microangiopathic manifestation. TTP was
      diagnosed, and plasma exchange and corticosteroids were initiated, with an
      excellent response. Subsequently, reduced disintegrin and metalloprotease with
      thrombospodin-2-like repeats (ADAMTS-13) activity and human immunodeficiency
      virus (HIV) were confirmed. Antiretroviral treatment was started as long-term
      management. At last follow-up, he continues in stable remission.

PMID- 29659974
TI  - Active Host Response to Algal Symbionts in the Sea Slug Elysia chlorotica.
AB  - Sacoglossan sea slugs offer fascinating systems to study the onset and
      persistence of algal-plastid symbioses. Elysia chlorotica is particularly
      noteworthy because it can survive for months, relying solely on energy produced
      by ingested plastids of the stramenopile alga Vaucheria litorea that are
      sequestered in cells lining its digestive diverticula. How this animal can
      maintain the actively photosynthesizing organelles without replenishment of
      proteins from the lost algal nucleus remains unknown. Here, we used RNA-Seq
      analysis to test the idea that plastid sequestration leaves a significant
      signature on host gene expression during E. chlorotica development. Our results
      support this hypothesis and show that upon exposure to and ingestion of V.
      litorea plastids, genes involved in microbe-associated molecular patterns and
      oxidative stress-response mechanisms are significantly up-regulated.
      Interestingly, our results with E. chlorotica mirror those found with corals that
      maintain dinoflagellates as intact cells in symbiosomes, suggesting parallels
      between these animal-algal symbiotic interactions.

PMID- 29659975
TI  - Synergistic Binding of bHLH Transcription Factors to the Promoter of the Maize
      NADP-ME Gene Used in C4 Photosynthesis Is Based on an Ancient Code Found in the
      Ancestral C3 State.
AB  - C4 photosynthesis has evolved repeatedly from the ancestral C3 state to generate
      a carbon concentrating mechanism that increases photosynthetic efficiency. This
      specialized form of photosynthesis is particularly common in the PACMAD clade of
      grasses, and is used by many of the world's most productive crops. The C4 cycle
      is accomplished through cell-type-specific accumulation of enzymes but cis
      elements and transcription factors controlling C4 photosynthesis remain largely
      unknown. Using the NADP-Malic Enzyme (NADP-ME) gene as a model we tested whether
      mechanisms impacting on transcription in C4 plants evolved from ancestral
      components found in C3 species. Two basic Helix-Loop-Helix (bHLH) transcription
      factors, ZmbHLH128 and ZmbHLH129, were shown to bind the C4NADP-ME promoter from
      maize. These proteins form heterodimers and ZmbHLH129 impairs trans-activation by
      ZmbHLH128. Electrophoretic mobility shift assays indicate that a pair of cis
      elements separated by a seven base pair spacer synergistically bind either
      ZmbHLH128 or ZmbHLH129. This pair of cis-elements is found in both C3 and C4
      Panicoid grass species of the PACMAD clade. Our analysis is consistent with this
      cis-element pair originating from a single motif present in the ancestral C3
      state. We conclude that C4 photosynthesis has co-opted an ancient C3 regulatory
      code built on G-box recognition by bHLH to regulate the NADP-ME gene. More
      broadly, our findings also contribute to the understanding of gene regulatory
      networks controlling C4 photosynthesis.

PMID- 29659976
TI  - A novel radiation-shielding undergarment using tungsten functional paper for
      patients with permanent prostate brachytherapy.
AB  - Tungsten functional paper (TFP) is a paper-based radiation-shielding material,
      which is lead-free and easy to cut. We developed a radiation protection
      undergarment using TFP for prostate cancer patients treated with permanent 125I
      seed implantation (PSI). The aim of this study was to evaluate the shielding
      ability of the undergarment with respect to household contacts and members of the
      public. Between October 2016 and April 2017, a total of 10 prostate cancer
      patients treated with PSI were enrolled in this prospective study. The external
      radiation exposure from each patient 1 day after PSI was measured with and
      without the undergarment. Measurements were performed using a survey meter at 100
      cm from the surface of the patient's body. The exposure rates were measured from
      five directions: anterior, anteriorly oblique, lateral, posteriorly oblique, and
      posterior. The measured radiation exposure rates without the undergarment,
      expressed as mean +/- standard deviation, from the anterior, anteriorly oblique,
      lateral, posteriorly oblique, and posterior directions were 1.28 +/- 0.43 MUSv/h,
      0.70 +/- 0.34 MUSv/h, 0.21 +/- 0.062 MUSv/h, 0.65 +/- 0.33 MUSv/h and 1.24 +/-
      0.41 MUSv/h, respectively. The undergarment was found to have (mean +/- standard
      deviation) shielding abilities of 88.7 +/- 5.8%, 44.0 +/- 42.1%, 50.6 +/- 15.9%,
      72.9 +/- 27.0% and 90.4 +/- 10.7% from the anterior, anteriorly oblique, lateral,
      posteriorly oblique, and posterior directions, respectively. In conclusion, this
      shielding undergarment is a useful device that has the potential to reduce
      radiation exposure for the general public and the patient's family.

PMID- 29659977
TI  - Quantification of variation in dose-volume parameters for the heart, pericardium
      and left ventricular myocardium during thoracic tumor radiotherapy.
AB  - Cardiac activity can induce dose-volume evaluation errors for cardiac structures.
      The purpose of this study was to quantify the variation in dose-volume parameters
      for the heart, pericardium and left ventricular myocardium (LVM) throughout the
      cardiac circle. The heart, pericardium and LVM of 22 patients were contoured on
      20 phases of electrocardiography-gated 4D computed tomography (4DCT) images
      acquired during breath-hold. Radiotherapy plans were designed on 0% phase of the
      4DCT images, and the dose distributions of the plans were imported into MIM
      Maestro and deformed to each phase to generate distributions for all phases.
      Variations in dose-volume parameters for the heart, pericardium and LVM were
      compared among different phases. The rates of variation in Dmean for the heart
      and pericardium were 3.33 +/- 1.04% and 2.66 +/- 1.15%, respectively. The mean
      values of the maximum difference in V5, V10, V20, V30 and V40 were all <2% for
      the heart and pericardium and were not statistically significant (P > 0.05). The
      rate of variation in Dmean for the LVM reached 87.05 +/- 38.34%, and the maximum
      differences in V5, V10, V20, V30 and V40 were 13.76 +/- 4.46%, 13.64 +/- 4.33%,
      12.84 +/- 4.55%, 11.62 +/- 4.85% and 3.63 +/- 2.56%, respectively; all
      differences were statistically significant (P < 0.05). Variations in dose-volume
      parameters were more significant in the LVM than in the heart and pericardium (P
      < 0.05). The dose-volume parameters for the LVM were significantly influenced by
      cardiac activity, whereas those for the heart and pericardium were not;
      therefore, individual dosimetric evaluation and limitation must be performed for
      the LVM.

PMID- 29659978
TI  - Consideration of the usefulness of a size-specific dose estimate in pediatric CT
      examination.
AB  - Computed tomography (CT) has recently been utilized in various medical settings,
      and technological advances have resulted in its widespread use. However, medical
      radiation exposure associated with CT scans accounts for the largest share of
      examinations using radiation; thus, it is important to understand the organ dose
      and effective dose in detail. The CT dose index and dose-length product are used
      to evaluate the organ dose. However, evaluations using these indicators fail to
      consider the age and body type of patients. In this study, we evaluated the
      effective dose based on the CT examination data of 753 patients examined at our
      hospital using the size-specific dose estimate (SSDE) method, which can calculate
      the exposure dose with consideration of the physique of a patient. The results
      showed a large correlation between the SSDE conversion factor and physique, with
      a larger exposure dose in patients with a small physique when a single scan is
      considered. Especially for children, the SSDE conversion factor was found to be 2
      or more. In addition, the patient exposed to the largest dose in this study was a
      10-year-old, who received 40.4 mSv (five series/examination). In the future, for
      estimating exposure using the SSDE method and in cohort studies, the diagnostic
      reference level of SSDE should be determined and a low-exposure imaging protocol
      should be developed to predict the risk of CT exposure and to maintain the
      quality of diagnosis with better radiation protection of patients.

PMID- 29659979
TI  - Redox-dependent control of nuclear transcription in plants.
AB  - Redox-dependent regulatory networks are affected by altered cellular or
      extracellular levels of reactive oxygen species (ROS). Perturbations of ROS
      production and scavenging homeostasis have a considerable impact on the nuclear
      transcriptome. While the regulatory mechanisms by which ROS modulate gene
      transcription in prokaryotes, lower eukaryotes, and mammalian cells are well
      established, new insights into the mechanism underlying redox control of gene
      expression in plants have only recently been known. In this review, we aim to
      provide an overview of the current knowledge on how ROS and thiol-dependent
      transcriptional regulatory networks are controlled. We assess the impact of redox
      perturbations and oxidative stress on transcriptome adjustments using cat2
      mutants as a model system and discuss how redox homeostasis can modify the
      various parts of the transcriptional machinery.

PMID- 29659980
TI  - Management of Bullet Emboli to the Heart and Great Vessels.
AB  - Introduction: Firearm-related injuries account for 20% of all injury-related
      deaths and are responsible for 105,000 injuries annually. The occurrence of
      bullet emboli to the heart is exceedingly rare. Given the rarity of emboli,
      controversy exists over management. The primary endpoint of this study is to
      establish a management algorithm for venous bullet emboli to the heart. Materials
      and methods: A literature search was performed using PubMed and Google Scholar
      with the following search terms: cardiac bullet embolus, cardiac missile embolus,
      and bullet embolus. Any discoverable case report(s) or series after 1960 were
      included in the review. The following data points were collected: age, sex,
      presentation, imaging, foreign body entry site, foreign body destination site,
      management, and outcomes. Results: Fifty-four articles met our search criteria. A
      total of 62 patients with thoracic venous bullet emboli were identified with the
      following distributions: right atrium (9.7%), right ventricle (54.8%), pulmonary
      arterial tree (32.3%), and intra-thoracic inferior vena cava (3.2%). Only 11.3%
      of patients had symptoms directly related to the cardiac venous emboli; however,
      all patients with acute symptoms underwent immediate intervention. Of those
      patients with bullet emboli to the pulmonary arterial tree, 45% were observed;
      whereas, only 20% with emboli to the right heart were observed. Those without
      signs or symptoms usually underwent an intervention (72.7%). Endovascular
      retrieval was successful in 53% of attempts. Of the endovascular attempts that
      failed, 28.6% were observed and 71.4% underwent open retrieval. Those who were
      asymptomatic and observed had no reported adverse sequelae during the follow-up.
      No mortalities were discovered in this review. Conclusion: Bullet emboli can
      prove to be a clinical challenge. Adjuncts such as X-ray, computed tomography,
      transthoracic, and/or transesophageal echocardiography help establish the emboli
      location. While observation in the asymptomatic patient is reasonable in some
      circumstances, most patients undergo removal. Removal of bullet cardiac emboli is
      safe with the availability of modern techniques.

PMID- 29659981
TI  - Neutral Variation in the Context of Selection.
AB  - In its initial formulation by Motoo Kimura, the neutral theory was concerned
      solely with the level of variability maintained by random genetic drift of
      selectively neutral mutations, and the rate of molecular evolution caused by the
      fixation of such mutations. The original theory considered events at a single
      genetic locus in isolation from the rest of the genome. It did not take long,
      however, for theoreticians to wonder whether selection at one or more loci might
      influence neutral variability at linked sites. Once DNA sequence variability
      could be studied, and especially when resequencing of whole genomes became
      possible, it became clear that patterns of neutral variability in genomes are
      affected by selection at linked sites, and that these patterns could advance our
      understanding of natural selection, and can be used to detect the action of
      selection in genomic regions, including selection much weaker than could be
      detected by direct measurements of the relative fitnesses of different genotypes.
      We outline the different types of processes that have been studied, in
      approximate order of their historical development.

PMID- 29659983
TI  - Inorganic carbon and pH dependency of photosynthetic rates in Trichodesmium.
AB  - Increasing atmospheric CO2 concentrations are leading to increases in dissolved
      CO2 and HCO3- concentrations and decreases in pH and CO32- in the world's oceans.
      There remain many uncertainties as to the magnitude of biological responses of
      key organisms to these chemical changes. In this study, we established the
      relationship between photosynthetic carbon fixation rates and pH, CO2, and HCO3-
      concentrations in the diazotroph, Trichodesmium erythraeum IMS101. Inorganic 14C
      assimilation was measured in TRIS-buffered artificial seawater medium where the
      absolute and relative concentrations of CO2, pH, and HCO3- were manipulated.
      First, we varied the total dissolved inorganic carbon concentration (TIC) (<0 to
      ~5 mM) at constant pH, so that ratios of CO2 and HCO3- remained relatively
      constant. Second, we varied pH (~8.54 to 7.52) at constant TIC, so that CO2
      increased whilst HCO3- declined. We found that 14C-assimilation could be
      described by the same function of CO2 for both approaches, but it showed
      different dependencies on HCO3- when pH was varied at constant TIC than when TIC
      was varied at constant pH. A numerical model of the carbon-concentrating
      mechanism (CCM) of Trichodesmium showed that carboxylation rates are modulated by
      HCO3- and pH. The decrease in assimilation of inorganic carbon (Ci) at low CO2,
      when TIC was varied, was due to HCO3- uptake limitation of the carboxylation
      rate. Conversely, when pH was varied, Ci assimilation declined due to a high-pH
      mediated increase in HCO3- and CO2 leakage rates, potentially coupled to other
      processes (uncharacterised within the CCM model) that restrict Ci assimilation
      rates under high-pH conditions.

PMID- 29659984
TI  - Molecular Biology and Evolution, Volume 35, Issue 4.

PMID- 29659982
TI  - Transcription start site analysis reveals widespread divergent transcription in
      D. melanogaster and core promoter-encoded enhancer activities.
AB  - Mammalian gene promoters and enhancers share many properties. They are composed
      of a unified promoter architecture of divergent transcripton initiation and gene
      promoters may exhibit enhancer function. However, it is currently unclear how
      expression strength of a regulatory element relates to its enhancer strength and
      if the unifying architecture is conserved across Metazoa. Here we investigate the
      transcription initiation landscape and its associated RNA decay in Drosophila
      melanogaster. We find that the majority of active gene-distal enhancers and a
      considerable fraction of gene promoters are divergently transcribed. We observe
      quantitative relationships between enhancer potential, expression level and core
      promoter strength, providing an explanation for indirectly related histone
      modifications that are reflecting expression levels. Lowly abundant unstable RNAs
      initiated from weak core promoters are key characteristics of gene-distal
      developmental enhancers, while the housekeeping enhancer strengths of gene
      promoters reflect their expression strengths. The seemingly separable layer of
      regulation by gene promoters with housekeeping enhancer potential is also
      indicated by chromatin interaction data. Our results suggest a unified promoter
      architecture of many D. melanogaster regulatory elements, that is universal
      across Metazoa, whose regulatory functions seem to be related to their core
      promoter elements.

PMID- 29659985
TI  - Grapevine fatty acid hydroperoxide lyase generates actin-disrupting volatiles and
      promotes defence-related cell death.
AB  - Fatty acid hydroperoxides can generate short-chained volatile aldehydes that may
      participate in plant defence. A grapevine hydroperoxide lyase (VvHPL1) clustering
      to the CYP74B class was functionally characterized with respect to a role in
      defence. In grapevine leaves, transcripts of this gene accumulated rapidly to
      high abundance in response to wounding. Cellular functions of VvHPL1 were
      investigated upon heterologous expression in tobacco BY-2 cells. A C-terminal
      green fluorescent protein (GFP) fusion of VvHPL1 was located in plastids. The
      overexpression lines were found to respond to salinity stress or the bacterial
      elicitor harpin by increasing cell death. This signal-dependent mortality
      response was mitigated either by addition of exogenous jasmonic acid or by
      treatment with diphenyleneiodonium (DPI), an inhibitor of NADPH oxidases. By
      feeding different substrates to recombinantly expressed enzyme, VvHPL1 could also
      be functionally classified as true 13-HPL. The cognate products generated by this
      13-HPL were cis-3-hexenal and trans-2-hexenal. Using a GFP-tagged actin marker
      line, one of these isomeric products, cis-3-hexenal, was found specifically to
      elicit a rapid disintegration of actin filaments. This response was not only
      observed in the heterologous system (tobacco BY-2), but also in a grapevine cell
      strain expressing this marker, as well as in leaf discs from an actin marker
      grape used as a homologous system. These results are discussed in the context of
      a role for VvHPL1 in a lipoxygenase-dependent signalling pathway triggering cell
      death-related defence that bifurcates from jasmonate-dependent basal immunity.

PMID- 29659987
TI  - An in vitro verification of strength estimation for moving an 125I source during
      implantation in brachytherapy.
AB  - This study aims to demonstrate the feasibility of a method for estimating the
      strength of a moving brachytherapy source during implantation in a patient.
      Experiments were performed under the same conditions as in the actual treatment,
      except for one point that the source was not implanted into a patient. The
      brachytherapy source selected for this study was 125I with an air kerma strength
      of 0.332 U (MUGym2h-1), and the detector used was a plastic scintillator with
      dimensions of 10 cm * 5 cm * 5 cm. A calibration factor to convert the counting
      rate of the detector to the source strength was measured and then the accuracy of
      the proposed method was investigated for a manually driven source. The accuracy
      was found to be under 10% when the shielding effect of additional needles for
      implantation at other positions was corrected, and about 30% when the shielding
      was not corrected. Even without shielding correction, the proposed method can
      detect dead/dropped source, implantation of a source with the wrong strength, and
      a mistake in the number of the sources implanted. Furthermore, when the
      correction was applied, the achieved accuracy came close to within 7% required to
      find the Oncoseed 6711 (125I seed with unintended strength among the commercially
      supplied values of 0.392, 0.462 and 0.533 U).

PMID- 29659986
TI  - Brassica yellows virus P0 protein impairs the antiviral activity of NbRAF2 in
      Nicotiana benthamiana.
AB  - In interactions between poleroviruses and their hosts, few cellular proteins have
      been identified that directly interact with the multifunctional virus P0 protein.
      To help explore the functions of P0, we identified a Brassica yellows virus
      genotype A (BrYV-A) P0BrA-interacting protein from Nicotiana benthamiana, Rubisco
      assembly factor 2 (NbRAF2), which localizes in the nucleus, cell periphery,
      chloroplasts, and stromules. We found that its C-terminal domain (amino acids 183
      211) is required for self-interaction. A split ubiquitin membrane-bound yeast two
      hybrid system and co-immunoprecipitation assays showed that NbRAF2 interacted
      with P0BrA, and co-localized in the nucleus and at the cell periphery.
      Interestingly, the nuclear pool of NbRAF2 decreased in the presence of P0BrA and
      during BrYV-A infection, and the P0BrA-mediated reduction of nuclear NbRAF2
      required dual localization of NbRAF2 in the chloroplasts and nucleus. Tobacco
      rattle virus-based virus-induced gene silencing of NbRAF2 promoted BrYV-A
      infection in N. benthamiana, and the overexpression of nuclear NbRAF2 inhibited
      BrYV-A accumulation. Potato leafroll virus P0PL also interacted with NbRAF2 and
      decreased its nuclear accumulation, indicating that NbRAF2 may be a common target
      of poleroviruses. These results suggest that nuclear NbRAF2 possesses antiviral
      activity against BrYV-A infection, and that BrYV-A P0BrA interacts with NbRAF2
      and alters its localization pattern to facilitate virus infection.

PMID- 29659988
TI  - VK-phantom male with 583 structures and female with 459 structures, based on the
      sectioned images of a male and a female, for computational dosimetry.
AB  - The anatomical structures in most phantoms are classified according to tissue
      properties rather than according to their detailed structures, because the tissue
      properties, not the detailed structures, are what is considered important.
      However, if a phantom does not have detailed structures, the phantom will be
      unreliable because different tissues can be regarded as the same. Thus, we
      produced the Visible Korean (VK) -phantoms with detailed structures (male, 583
      structures; female, 459 structures) based on segmented images of the whole male
      body (interval, 1.0 mm; pixel size, 1.0 mm2) and the whole female body (interval,
      1.0 mm; pixel size, 1.0 mm2), using house-developed software to analyze the text
      string and voxel information for each of the structures. The density of each
      structure in the VK-phantom was calculated based on Virtual Population and a
      publication of the International Commission on Radiological Protection. In the
      future, we will standardize the size of each structure in the VK-phantoms. If the
      VK-phantoms are standardized and the mass density of each structure is precisely
      known, researchers will be able to measure the exact absorption rate of
      electromagnetic radiation in specific organs and tissues of the whole body.

PMID- 29659989
TI  - Estimating Improved Partitioning Schemes for Ultraconserved Elements.
AB  - Ultraconserved (UCEs) are popular markers for phylogenomic studies. They are
      relatively simple to collect from distantly-related organisms, and contain
      sufficient information to infer relationships at almost all taxonomic levels.
      Most studies of UCEs use partitioning to account for variation in rates and
      patterns of molecular evolution among sites, for example by estimating an
      independent model of molecular evolution for each UCE. However, rates and
      patterns of molecular evolution vary substantially within as well as between
      UCEs, suggesting that there may be opportunities to improve how UCEs are
      partitioned for phylogenetic inference. We propose and evaluate new partitioning
      methods for phylogenomic studies of UCEs: Sliding-Window Site Characteristics
      (SWSC), and UCE Site Position (UCESP). The first method uses site characteristics
      such as entropy, multinomial likelihood, and GC content to generate partitions
      that account for heterogeneity in rates and patterns of molecular evolution
      within each UCE. The second method groups together nucleotides that are found in
      similar physical locations within the UCEs. We examined the new methods with
      seven published data sets from a variety of taxa. We demonstrate the UCESP method
      generates partitions that are worse than other strategies used to partition UCE
      data sets (e.g., one partition per UCE). The SWSC method, particularly when based
      on site entropies, generates partitions that account for within-UCE heterogeneity
      and leads to large increases in the model fit. All of the methods, code, and data
      used in this study, are available from
      https://github.com/Tagliacollo/PartitionUCE. Simplified code for implementing the
      best method, the SWSC-EN, is available from
      https://github.com/Tagliacollo/PFinderUCE-SWSC-EN.

PMID- 29659990
TI  - Erratum: In vitro activity of isavuconazole against fluconazole-resistant
      isolates of Histoplasma capsulatum.

PMID- 29659992
TI  - Neutral Theory: From Complex Population History to Natural Selection and
      Sociocultural Phenomena in Human Populations.
AB  - Here, we present a synthetic view on how Kimura's Neutral theory has helped us
      gaining insight on the different evolutionary forces that shape human evolution.
      We put this perspective in the frame of recent emerging challenges: the use of
      whole genome data for reconstructing population histories, natural selection on
      complex polygenic traits, and integrating cultural processes in human evolution.

PMID- 29659991
TI  - Consequences of Asexuality in Natural Populations: Insights from Stick Insects.
AB  - Recombination is a fundamental process with significant impacts on genome
      evolution. Predicted consequences of the loss of recombination include a reduced
      effectiveness of selection, changes in the amount of neutral polymorphisms
      segregating in populations, and an arrest of GC-biased gene conversion. Although
      these consequences are empirically well documented for nonrecombining genome
      portions, it remains largely unknown if they extend to the whole genome scale in
      asexual organisms. We identify the consequences of asexuality using de novo
      transcriptomes of five independently derived, obligately asexual lineages of
      stick insects, and their sexual sister-species. We find strong evidence for
      higher rates of deleterious mutation accumulation, lower levels of segregating
      polymorphisms and arrested GC-biased gene conversion in asexuals as compared with
      sexuals. Taken together, our study conclusively shows that predicted consequences
      of genome evolution under asexuality can indeed be found in natural populations.

PMID- 29659993
TI  - Neutral Theory and Phenotypic Evolution.
AB  - Although the neutral theory of molecular evolution was proposed to explain DNA
      and protein sequence evolution, in principle it could also explain phenotypic
      evolution. Nevertheless, overall, phenotypes should be less likely than genotypes
      to evolve neutrally. I propose that, when phenotypic traits are stratified
      according to a hierarchy of biological organization, the fraction of evolutionary
      changes in phenotype that are adaptive rises with the phenotypic level
      considered. Consistently, molecular traits are frequently found to evolve
      neutrally whereas a large, random set of organismal traits were recently reported
      to vary largely adaptively. Many more studies of unbiased samples of phenotypic
      traits are needed to test the general validity of this hypothesis.

PMID- 29659994
TI  - Resident and Staff Satisfaction of Pediatric Graduate Medical Education Training
      on Transition to Adult Care of Medically Complex Patients.
AB  - Introduction: This study aims to describe the quantity and satisfaction current
      residents and experienced pediatricians have with graduate medical education on
      transitioning medically complex patients to adult care. There is an increasing
      need for transitioning medically complex adolescents to adult care. Over 90% now
      live into adulthood and require transition to adult healthcare providers. The
      2010 National Survey of Children with Special Health Care Needs found that only
      40% of youth 12-17 yr receive the necessary services to appropriately transition
      to adult care. Materials and Methods: Prospective, descriptive, anonymous, web
      based survey of pediatric residents and staff pediatricians at Army pediatric
      residency training programs was sent in March 2017. Questions focused on
      assessing knowledge of transition of care, satisfaction with transition training,
      and amount of education on transition received during graduate medical education
      training. Results: Of the 145 responders (310 potential responders, 47% response
      rate), transition was deemed important with a score of 4.3 out of 5. The comfort
      level with transition was rated 2.6/5 with only 4.2% of participants receiving
      formal education during residency. The most commonly perceived barriers to
      implementing a curriculum were time constraints and available resources. Of the
      five knowledge assessment questions, three had a correct response rate of less
      than 1/3. Conclusions: The findings show the disparity between the presence of
      and perceived need for a formal curriculum on transitioning complex pediatric
      patients to adult care. This study also highlighted the knowledge gap of the
      transition process for novice and experienced pediatricians alike.

PMID- 29659995
TI  - The Importance of Wall Apposition in Flow Diverters.
AB  - BACKGROUND: It is assumed that high pore densities in flow diverters (FDs) are
      beneficial for intracranial aneurysm (IA) healing. However, various animal
      studies are not conclusive on the issue, suggesting that other factors are in
      play. One important factor might be wall apposition. OBJECTIVE: To (1) determine
      the relationship between FD pore density and aneurysm occlusion, and (2)
      determine the relationship between FD wall apposition and aneurysm occlusion.
      METHODS: Saccular aneurysms were microsurgically created in the aorta of 36
      Wistar rats. Twelve rats received a low pore density FD (10 pores/mm2), 12 rats
      received a high pore density FD (23 pores/mm2), and the remaining 12 rats served
      as a control group. Six animals from each group were sacrificed 1 and 3 mo after
      surgery. We determined aneurysm occlusion, the number of struts not in contact
      with the aorta wall, and the average distance from malapposed struts to aorta
      wall through histology. RESULTS: No significant differences were found in
      aneurysm occlusion between the low pore density and high pore density groups (P >
      .05) after 1 and 3 mo of follow-up. The average number of malapposed struts was
      lower for the occluded aneurysm group (4.4 +/- 1.9) compared to the nonoccluded
      aneurysm group (7.7 +/- 2.6, P < .01). The average distance between malapposed
      struts and parent artery wall was lower for the occluded aneurysm group (33.9 MUm
      +/- 11.5 MUm) than for the nonoccluded aneurysm group (48.7 MUm +/- 18.8 MUm, P <
      .05). CONCLUSION: Wall apposition is more important than pore density for
      aneurysm occlusion.

PMID- 29659996
TI  - My favourite flowering image: an Arabidopsis inflorescence expressing fluorescent
      reporters for the APETALA3 and SUPERMAN genes.

PMID- 29659997
TI  - Image quality improvement in cone-beam CT using the super-resolution technique.
AB  - This study was conducted to improve cone-beam computed tomography (CBCT) image
      quality using the super-resolution technique, a method of inferring a high
      resolution image from a low-resolution image. This technique is used with two
      matrices, so-called dictionaries, constructed respectively from high-resolution
      and low-resolution image bases. For this study, a CBCT image, as a low-resolution
      image, is represented as a linear combination of atoms, the image bases in the
      low-resolution dictionary. The corresponding super-resolution image was inferred
      by multiplying the coefficients and the high-resolution dictionary atoms
      extracted from planning CT images. To evaluate the proposed method, we computed
      the root mean square error (RMSE) and structural similarity (SSIM). The resulting
      RMSE and SSIM between the super-resolution images and the planning CT images
      were, respectively, as much as 0.81 and 1.29 times better than those obtained
      without using the super-resolution technique. We used super-resolution technique
      to improve the CBCT image quality.

PMID- 29659999
TI  - Increased Body Mass Index Associated With Reduced Risk of Delayed Cerebral
      Ischemia and Subsequent Infarction After Aneurysmal Subarachnoid Hemorrhage.
AB  - BACKGROUND: Increased body mass index (BMI) may be protective against cerebral
      ischemia in certain clinical contexts. OBJECTIVE: To investigate whether
      increased BMI was associated with delayed cerebral ischemia (DCI) and subsequent
      infarction after aneurysmal subarachnoid hemorrhage (aSAH). METHODS: We
      retrospectively reviewed the clinical course of patients presenting to our
      institution for management of aSAH. Patient were segregated according to BMI< or
      >=29.4, a value determined by Classification and Regression Tree analysis.
      Predictors of DCI and delayed infarction were identified using stepwise
      multivariate logistic regression analysis. RESULTS: There were 161 patients
      included for analysis. Average BMI within our patient cohort was 28.9, with 67
      patients presenting with a BMI of >=29.4 on admission. DCI occurred in 50
      patients (31.1%) and was complicated by delayed infarction in 15 patients (9.3%).
      On stepwise multivariate analysis, BMI >= 29.4 was independently associated with
      reduced likelihood of DCI (odds ratio [OR] 0.42, 95% confidence interval [CI]
      0.18-0.92) and delayed infarction (OR 0.13, 95% CI 0.02-0.61; P = .008).
      Increasing maximum flow velocity on transcranial Doppler ultrasound was
      independently associated with increased odds of both DCI (Unit OR 1.19, 95% CI
      1.09-1.30; P < .001) and delayed infarction (Unit OR 1.31, 95% CI 1.13-1.56; P <
      .001), while intracerebral hemorrhage was independently associated with increased
      odds of delayed infarction (OR 6.99, 95% CI 1.82-30.25; P = .005). CONCLUSION: We
      report an association between elevated BMI and reduced incidence of DCI and
      delayed infarction, suggesting a protective effect of increasing BMI on the risk
      of ischemic complications after aSAH.

PMID- 29659998
TI  - The arginine methyltransferase CARM1 represses p300*ACT*CREMtau activity and is
      required for spermiogenesis.
AB  - CARM1 is a protein arginine methyltransferase (PRMT) that has been firmly
      implicated in transcriptional regulation. However, the molecular mechanisms by
      which CARM1 orchestrates transcriptional regulation are not fully understood,
      especially in a tissue-specific context. We found that Carm1 is highly expressed
      in the mouse testis and localizes to the nucleus in spermatids, suggesting an
      important role for Carm1 in spermiogenesis. Using a germline-specific conditional
      Carm1 knockout mouse model, we found that it is essential for the late stages of
      haploid germ cell development. Loss of Carm1 led to a low sperm count and
      deformed sperm heads that can be attributed to defective elongation of round
      spermatids. RNA-seq analysis of Carm1-null spermatids revealed that the
      deregulated genes fell into similar categories as those impacted by p300-loss,
      thus providing a link between Carm1 and p300. Importantly, p300 has long been
      known to be a major Carm1 substrate. We found that CREMtau, a key testis-specific
      transcription factor, associates with p300 through its activator, ACT, and that
      this interaction is negatively regulated by the methylation of p300 by Carm1.
      Thus, high nuclear Carm1 levels negatively impact the p300*ACT*CREMtau axis
      during late stages of spermiogenesis.

PMID- 29660000
TI  - Spermatogonial behavior in marmoset: a new generation, their kinetics and niche.
AB  - STUDY QUESTION: Could a more detailed evaluation of marmoset spermatogonial
      morphology, kinetics and niches using high-resolution light microscopy (HRLM)
      lead to new findings? SUMMARY ANSWER: Three subtypes of marmoset undifferentiated
      spermatogonia, which were not evenly distributed in terms of number and position
      along the basal membrane, and an extra premeiotic cell division not present in
      humans were identified using HRLM. WHAT IS KNOWN ALREADY: The seminiferous
      epithelium cycle (SEC) of marmosets is divided into nine stages when based on the
      acrosome system, and several spermatogenic stages can usually be recognized
      within the same tubular cross-section. Three spermatogonial generations have been
      previously described in marmosets: types Adark, Apale and B spermatogonia. STUDY
      DESIGN, SIZE, DURATION: Testes from five adult Callithrix penicillata were fixed
      by glutaraldehyde perfusion via the cardiac route and embedded in Araldite
      plastic resin for HRLM evaluation. Semi-thin sections (1 MUm) were analyzed
      morphologically and morphometrically to evaluate spermatogonial morphology and
      kinetics (number, mitosis and apoptosis), spermatogenesis efficiency and the
      spermatogonial niche. PARTICIPANTS/MATERIALS, SETTING, METHODS: Shape and nuclear
      diameter, the presence and distribution of heterochromatin, the granularity of
      the euchromatin, as well as the number, morphology and degree of nucleolar
      compaction were observed for morphological characterization. Kinetics analyses
      were performed for all spermatogonial subtypes and preleptotene spermatocytes,
      and their mitosis and apoptosis indexes determined across all SEC stages.
      Spermatogenesis parameters (mitotic, meiotic, Sertoli cell workload and general
      spermatogenesis efficiency) were determined through the counting of Adark and
      Apale spermatogonia, preleptotene and pachytene primary spermatocytes, round
      spermatids, and Sertoli cells at stage IV of the SEC. MAIN RESULTS AND THE ROLE
      OF CHANCE: This is the first time that a study in marmosets demonstrates: the
      existence of a new spermatogonial generation (B2); the presence of two subtypes
      of Adark spermatogonia with (AdVac) and without (AdNoVac) nuclear rarefaction
      zones; the peculiar behavior of AdVac spermatogonia across the stages of the SEC,
      suggesting that they are quiescent stem spermatogonia; and that AdVac
      spermatogonia are located close to areas in which blood vessels, Leydig cells and
      macrophages are concentrated, suggesting a niche area for these cells. LARGE
      SCALE DATA: Not applicable. LIMITATIONS, REASONS FOR CAUTION: The C. penicillata
      spermatogonial kinetics evaluated here consider spermatogonial number across the
      SEC and their mitotic and apoptotic figures identified in HRLM sections.
      Therefore, caution is required when comparing absolute values between species.
      Although morphometric evaluation has suggested that AdVac spermatogonia are stem
      cells, a functional proof of this is still missing. It is known that parameters
      of the spermatogenic process in C. penicillata have similarities with those of
      the common marmoset C. jacchus, however, a detailed study of spermatogonial
      morphology, kinetics and niche has not yet been performed in C. jacchus, and a
      full comparison of the two species is not possible. WIDER IMPLICATIONS OF THE
      FINDINGS: Our findings in C. penicillata contribute to a better understanding of
      the spermatogonial behavior and spermatogenesis efficiency in non-human primates.
      Given the phylogenetic closeness of the marmoset to the human species, similar
      processes might occur in humans. Therefore, marmosets may be an excellent model
      for studies regarding human testicular biology, fertility and related disorders.
      STUDY FUNDING/COMPETING INTEREST(S): Experiments were partially supported by
      Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), Fundacao de
      Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG) and Conselho Nacional de
      Desenvolvimento Cientifico e Tecnologico (CNPq). The authors declare that there
      are no conflicts of interest.

PMID- 29660001
TI  - Translatome analysis at the egg-to-embryo transition in sea urchin.
AB  - Early embryogenesis relies on the translational regulation of maternally stored
      mRNAs. In sea urchin, fertilization triggers a dramatic rise in translation
      activity, necessary for the onset of cell division. Here, the full spectrum of
      the mRNAs translated upon fertilization was investigated by polysome profiling
      and sequencing. The translatome of the early sea urchin embryo gave a complete
      picture of the polysomal recruitment dynamics following fertilization. Our
      results indicate that only a subset of maternal mRNAs were selectively recruited
      onto polysomes, with over-represented functional categories in the translated
      set. The increase in translation upon fertilization depends on the formation of
      translation initiation complexes following mTOR pathway activation. Surprisingly,
      mTOR pathway inhibition differentially affected polysomal recruitment of the
      newly translated mRNAs, which thus appeared either mTOR-dependent or mTOR
      independent. Therefore, our data argue for an alternative to the classical cap
      dependent model of translation in early development. The identification of the
      mRNAs translated following fertilization helped assign translational activation
      events to specific mRNAs. This translatome is the first step to a comprehensive
      analysis of the molecular mechanisms governing translation upon fertilization and
      the translational regulatory networks that control the egg-to-embryo transition
      as well as the early steps of embryogenesis.

PMID- 29660002
TI  - Convergent Acquisition of Nonembryonic Development in Styelid Ascidians.
AB  - Asexual propagation and whole body regeneration are forms of nonembryonic
      development (NED) widespread across animal phyla and central in life history and
      evolutionary diversification of metazoans. Whereas it is challenging to
      reconstruct the gains or losses of NED at large phylogenetic scale, comparative
      studies could benefit from being conducted at more restricted taxonomic scale, in
      groups for which phylogenetic relationships are well established. The ascidian
      family of Styelidae encompasses strictly sexually reproducing solitary forms as
      well as colonial species that combine sexual reproduction with different forms of
      NED. To date, the phylogenetic relationships between colonial and solitary
      styelids remain controversial and so is the pattern of NED evolution. In this
      study, we built an original pipeline to combine eight genomes with 18 de novo
      assembled transcriptomes and constructed data sets of unambiguously orthologous
      genes. Using a phylogenomic super-matrix of 4,908 genes from these 26 tunicates
      we provided a robust phylogeny of this family of chordates, which supports two
      convergent acquisitions of NED. This result prompted us to further describe the
      budding process in the species Polyandrocarpa zorritensis, leading to the
      discovery of a novel mechanism of asexual development. Whereas the pipeline and
      the data sets produced can be used for further phylogenetic reconstructions in
      tunicates, the phylogeny provided here sets an evolutionary framework for future
      experimental studies on the emergence and disappearance of complex characters
      such as asexual propagation and whole body regeneration.

PMID- 29660003
TI  - Temperature and nitrogen supply interact to determine protein distribution
      gradients in the wheat grain endosperm.
AB  - Gradients exist in the distribution of storage proteins in the wheat (Triticum
      aestivum) endosperm and determine the milling properties and protein recovery
      rate of the grain. A novel image analysis technique was developed to quantify
      both the gradients in protein concentration, and the size distribution of protein
      bodies within the endosperm of wheat plants grown under two different (20 or 28 
      degrees C) post-anthesis temperatures, and supplied with a nutrient solution with
      either high or low nitrogen content. Under all treatment combinations, protein
      concentration was greater in the endosperm cells closest to the aleurone layer
      and decreased towards the centre of the two lobes of the grain, i.e. a negative
      gradient. This was accompanied by a decrease in size of protein bodies from the
      outer to the inner endosperm layers in all but one of the treatments. Elevated
      post-anthesis temperature had the effect of increasing the magnitude of the
      negative gradients in both protein concentration and protein body size, whilst
      limiting nitrogen supply decreased the gradients.

PMID- 29660004
TI  - Renal transplant outcomes and de novo donor-specific anti-human leukocyte antigen
      antibodies: a systematic review.
AB  - Background: Pre-transplant donor-specific anti-human leukocyte antigen antibodies
      (DSAs) are known risk factors for acute rejection and reduced graft survival
      after kidney transplantation. DSAs may also develop de novo DSAs (dnDSAs) after
      transplantation but the clinical implications of these antibodies remain
      uncertain. Methods: We undertook a systematic review of observational studies
      that examined the association between dnDSAs and graft and patient outcomes
      (through August 2017) with the Grading of Recommendations Assessment, Development
      and Evaluation (GRADE) system of reporting used to assess the quality of evidence
      available. Results: Thirty-six studies involving 10 535 transplant recipients
      were eligible. There was moderate quality evidence that transplant recipients who
      developed dnDSAs had increased risks of acute antibody-mediated rejection (AMR)
      [relative risk (RR) 9.66; 95% confidence interval (CI) 6.79-13.73, 16 studies, n
      = 4174]. For all other outcomes, the evidence was low to very low due to moderate
      high heterogeneity and low study quality (acute cellular rejection, RR 2.92; 95%
      CI 2.16-3.94, 22 studies, n = 4991, low-quality evidence; chronic AMR and
      transplant glomerulopathy RR 6.78; 95% CI 4.31-10.66, 3 studies, n = 1617, very
      low-quality evidence; and graft loss RR 4.95; 95% CI 3.81-6.43, 19 studies, n =
      5473, low-quality evidence). Meta-regression indicated that deceased kidney
      donation (R2 = 1.00, P < 0.001) and region of study conduction (R2 = 0.50, P =
      0.005) modified associations between dnDSAs and outcomes. Conclusions: dnDSAs are
      associated with increased risks of adverse graft and patient outcomes after
      kidney transplantation, but estimation uncertainty of the augmented risks exist
      due to limitations such as heterogeneity within the existing literature.
      Therapeutic interventions targeted to eliminate or prevent these antibodies
      evaluated in randomized controlled trials are needed to establish whether dnDSAs
      are causal to transplantation outcomes.

PMID- 29660005
TI  - Volumetric response quantified using T1 subtraction predicts long-term survival
      benefit from cabozantinib monotherapy in recurrent glioblastoma.
AB  - Background: To overcome challenges with traditional response assessment in anti
      angiogenic agents, the current study uses T1 subtraction maps to quantify
      volumetric radiographic response in monotherapy with cabozantinib, an orally
      bioavailable tyrosine kinase inhibitor with activity against vascular endothelial
      growth factor receptor 2 (VEGFR2), hepatocyte growth factor receptor (MET), and
      AXL, in an open-label, phase II trial in patients with recurrent glioblastoma
      (GBM) (NCT00704288). Methods: A total of 108 patients with adequate imaging data
      and confirmed recurrent GBM were included in this retrospective study from a
      phase II multicenter trial of cabozantinib monotherapy (XL184-201) at either 100
      mg (N = 87) or 140 mg (N = 21) per day. Contrast enhanced T1-weighted digital
      subtraction maps were used to define volume of contrast-enhancing tumor at
      baseline and subsequent follow-up time points. Volumetric radiographic response
      (>65% reduction in contrast-enhancing tumor volume from pretreatment baseline
      tumor volume sustained for more than 4 wk) was tested as an independent predictor
      of overall survival (OS). Results: Volumetric response rate for all therapeutic
      doses was 38.9% (41.4% and 28.6% for 100 mg and 140 mg doses, respectively). A
      log-linear association between baseline tumor volume and OS (P = 0.0006) and a
      linear correlation between initial change in tumor volume and OS (P = 0.0256)
      were observed. A significant difference in OS was observed between responders
      (median OS = 20.6 mo) and nonresponders (median OS = 8.0 mo) (hazard ratio [HR] =
      0.3050, P < 0.0001). Multivariable analyses showed that continuous measures of
      baseline tumor volume (HR = 1.0233, P < 0.0001) and volumetric response (HR =
      0.2240, P < 0.0001) were independent predictors of OS. Conclusions: T1
      subtraction maps provide value in determining response in recurrent GBM treated
      with cabozantinib and correlated with survival benefit.

PMID- 29660007
TI  - Uric acid is not associated with diabetic nephropathy and other complications in
      type 1 diabetes.
AB  - Background: To examine the association between plasma uric acid (UA) and the
      presence of diabetic complications including diabetic nephropathy and
      cardiovascular risk factors in patients with type 1 diabetes. Methods: This
      study, which is cross-sectional in design, included 676 Caucasian type 1 diabetes
      patients from the Steno Diabetes Center Copenhagen. Participants with UA within
      the three lowest sex-specific quartiles were compared with participants with
      levels in the highest quartile. Unadjusted and adjusted linear regression
      analyses were applied. Adjustment included sex, age, diabetes duration, body mass
      index, high-density lipoprotein cholesterol, smoking, haemoglobin A1c, 24-h pulse
      pressure, urinary albumin excretion rate (UAER), estimated glomerular filtration
      rate (eGFR) and treatment with renin-angiotensin-aldosterone system blockers.
      Results: Of the 676 patients, 372 (55%) were male, mean +/- SD age was 55 +/- 13
      years and eGFR was 82 +/- 26 mL/min/1.73 m2. The median UA was 0.30
      (interquartile range 0.23-0.37) mmol/L. UA in the upper sex-specific quartile was
      associated with lower eGFR, higher UAER and carotid-femoral pulse wave velocity
      and lower 24 h and daytime diastolic blood pressure (BP) in unadjusted analyses
      (P < 0.001). Moreover, UA in the upper sex-specific quartile was associated with
      higher nighttime systolic BP and the presence of cardiovascular disease in
      unadjusted analyses (P <= 0.01), but significance was lost after adjustment (P >=
      0.17). UA was higher across the retinopathy groups [nil (n = 142), simplex (n =
      277), proliferative (n = 229) and blind (n = 19)] in unadjusted analyses (P <
      0.0001), but not after adjustment (P = 0.12). Patients with an accelerated
      decline in eGFR (>=3 mL/min/year) had significantly higher UA at baseline (P =
      0.006) compared with slow decliners (<3 mL/min/year), but significance was lost
      after adjustment (P = 0.10). Conclusions: In type 1 diabetes patients, higher UA
      was associated with lower kidney function and other diabetic complications. The
      association between higher UA and lower eGFR and lower diastolic BP was
      independent of traditional risk factors.

PMID- 29660006
TI  - Validation of postoperative residual contrast-enhancing tumor volume as an
      independent prognostic factor for overall survival in newly diagnosed
      glioblastoma.
AB  - Background: In the current study, we pooled imaging data in newly diagnosed
      glioblastoma (GBM) patients from international multicenter clinical trials,
      single institution databases, and multicenter clinical trial consortiums to
      identify the relationship between postoperative residual enhancing tumor volume
      and overall survival (OS). Methods: Data from 1511 newly diagnosed GBM patients
      from 5 data sources were included in the current study: (i) a single institution
      database from UCLA (N = 398; Discovery); (ii) patients from the Ben and Cathy Ivy
      Foundation for Early Phase Clinical Trials Network Radiogenomics Database (N =
      262 from 8 centers; Confirmation); (iii) the chemoradiation placebo arm from an
      international phase III trial (AVAglio; N = 394 from 120 locations in 23
      countries; Validation); (iv) the experimental arm from AVAglio examining
      chemoradiation plus bevacizumab (N = 404 from 120 locations in 23 countries;
      Exploratory Set 1); and (v) an Alliance (N0874) phase I/II trial of vorinostat
      plus chemoradiation (N = 53; Exploratory Set 2). Postsurgical, residual enhancing
      disease was quantified using T1 subtraction maps. Multivariate Cox regression
      models were used to determine influence of clinical variables, O6-methylguanine
      DNA methyltransferase (MGMT) status, and residual tumor volume on OS. Results: A
      log-linear relationship was observed between postoperative, residual enhancing
      tumor volume and OS in newly diagnosed GBM treated with standard chemoradiation.
      Postoperative tumor volume is a prognostic factor for OS (P < 0.01), regardless
      of therapy, age, and MGMT promoter methylation status. Conclusion: Postsurgical,
      residual contrast-enhancing disease significantly negatively influences survival
      in patients with newly diagnosed GBM treated with chemoradiation with or without
      concomitant experimental therapy.

PMID- 29660008
TI  - Exosomal miR-214 from endometrial stromal cells inhibits endometriosis fibrosis.
AB  - STUDY QUESTION: Is it possible to improve fibrosis in endometriosis by microRNA
      214 delivery in exosomes? SUMMARY ANSWER: Upregulation of miR-214 may inhibit
      fibrogenesis and its delivery by exosomes derived from ectopic endometrial
      stromal cells (ESCs), offers an alternative therapeutic approach for
      endometriosis fibrosis. WHAT IS KNOWN ALREADY: Fibrosis is the primary
      pathological feature of endometriosis. MiR-214 plays an important role in
      fibrotic disease. Connective tissue growth factor (CTGF) is a critical fibrogenic
      mediator of miR-214. The expression of miR-214 is decreased in ectopic ESCs
      compared with normal ESCs. miRNAs are a natural cargo of exosomes and these could
      be exploited as carriers of miRNA in replacement therapy. STUDY DESIGN, SIZE,
      DURATION: Paired eutopic and ectopic endometrial tissue samples were obtained
      from 10 women with ovarian endometrioma. ESCs and epithelial cells from both were
      cultured in vitro. RT-PCR, western blot and immunohistochemistry were used to
      study the effect of transfection with miR-214 mimics on CTGF expression and
      fibrogenesis respectively, with and without TGFbeta stimulation. Exosomes were
      isolated from ectopic ESCs and Endometrioma tissue was isolated from four
      patients, dispersed an injected (ip) into nude mice and allowed to implant. The
      mice were treated with miR-214-enriched exosomes or controls to confirm the
      effect of inhibiting CTGF overexpression on endometriosis fibrosis.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: The primary ectopic ESCs were
      transfected with miR-214 mimics. The levels of miR-214, CTGF and fibrotic markers
      were measured by RT-PCR and Immunohistochemistry. A mouse model of endometriosis
      was established by ip injection of human ectopic endometrial tissues into nude
      mice. MiR-214-enriched exosomes were injected into the mice and endometriotic
      lesions were measured on Day 28. Changes in fibrosis of the endometriotic
      implants were studied by histopathological staining. MAIN RESULTS AND THE ROLE OF
      CHANCE: CTGF and fibrotic markers upregulation in endometriosis is associated
      with a reciprocal down-regulation of miR-214. By using miR-214 mimics and
      antagomirs to investigate expression of fibrotic markers, we found that increased
      production of miR-214 reduced Collagen alphaI and CTGF expression in
      endometriosis stromal and endometrial epithelial cells in response to fibrosis
      inducing stimuli (P < 0.001 versus non-treatment). Ectopic ESCs yielded nano
      sized exosomes which expressed miR-214. Loading exosomes with miR-214 mimics and
      injecting them into an experimental endometriosis mouse model resulted in a
      decrease in the expression of fibrosis-associated proteins (P < 0.001 versus PBS
      control group). LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: We only
      isolated exosomes from ectopic ESCs, whether this is the optimum source requires
      further study. WIDER IMPLICATIONS OF THE FINDINGS: Upregulation of miRNA-214
      potentially offers an alternative therapeutic approach for endometriosis
      fibrosis. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by grants
      from the National Natural Science Foundation of China (Grant no. 81771549 Jinwei
      Miao). The authors declare that there is no conflict of interest.

PMID- 29660009
TI  - Critical Care in the Military Health System: A 24-h Point Prevalence Study.
AB  - Background: Healthcare expenditures are a significant economic cost with critical
      care services constituting one of its largest components. The Military Health
      System (MHS) is the largest, global healthcare system of its kind. In this
      project, we sought to describe critical care services and the patients who
      receive them in the MHS. Methods: We surveyed 26 military treatment facilities
      (MTFs) representing 38 critical care services or intensive care units (ICUs).
      MTFs with multiple ICUs and critical care services responded to the survey as
      services (e.g., surgical or medical ICU service), whereas MTFs with only one ICU
      responded as a unit and gave information about all types of patients (i.e.,
      medical and surgical). Our survey was divided into an administrative portion and
      a 24-h point prevalence survey of patients and patient care. The administrative
      portion is reported separately in this journal. The 24-h point prevalence survey
      collected information about all patients present in, admitted to, or discharged
      from participating services/units during the same 24-h period in December 2014.
      The survey was anonymous and protected health information was not collected.
      Findings: Sixteen MTFs (69%) and 27 ICU services/units (71%) returned the point
      prevalence survey. MTFs with >200 beds (n = 3, 22%) were categorized as "high
      capacity centers" (HCCs) whereas those with <=200 beds (n = 13, 78%) were
      characterized as low capacity centers (LCCs). Two MTFs (one HCC and one LCC)
      returned only administrative data. The remaining 16 MTFs reported data about 151
      patients. In all, 100 (67%) of the patients were at three HCCs during this study
      period. One HCC accounted for 39% (59 patients) of all patient care during this
      study. Most patients were cared for in mixed medical/surgical ICUs (34.4%),
      followed by medical (21.2%), surgical (18.5%), trauma (11.9%), cardiac (7.9%),
      and burn (6.0%) ICUs. The most common medical indication for admission was
      cardiac followed by general medical. The most common surgical indications for
      admission were trauma, other, and cardiothoracic surgery. The average APACHE II
      score of all patients across both LCCs and HCCs was 11 +/- 8.1 (8 +/- 7.8 vs. 13
      +/- 7.7 p = 0.008). The lower acuity of patients in this study is reflected in a
      high turnover rate, low rate of arterial and central line placements (33%), and
      low rates of life support (all types, 30%; mechanical ventilation only, 21.2%;
      noninvasive mechanic ventilation only, 7.9%; and vasoactive medications, 6.6%).
      Thirty-five (23.2%) patients within the study were affected by a total of 57
      complications. The three most common complications experienced were acute kidney
      injury, bleeding, and sepsis. Discussion: This is the first detailed report about
      MHS critical care services and the patients receiving care. It describes a low
      acuity ICU patient population, concentrated at larger MTFs. This study highlights
      the need for the establishment of a system that allows for the continuous
      collection of high priority information about clinical care in the MHS in order
      to facilitate implementation of standardized protocols and process improvements.

PMID- 29660010
TI  - Costs for Breast Cancer Care in the Military Health System: An Analysis by
      Benefit Type and Care Source.
AB  - Introduction: Breast cancer care imposes a significant financial burden to U.S.
      healthcare systems. Health services factors, such as insurance benefit type and
      care source, may impact costs to the health system. Beneficiaries in the U.S.
      Military Health System (MHS) have universal healthcare coverage and access to a
      network of military facilities (direct care) and private practices (purchased
      care). This study aims to quantify and compare breast cancer care costs to the
      MHS by insurance benefit type and care source. Materials and Methods: We
      conducted a retrospective analysis of data linked between the MHS data repository
      administrative claims and central cancer registry databases. The institutional
      review boards of the Walter Reed National Military Medical Center, the Defense
      Health Agency, and the National Institutes of Health Office of Human Subjects
      Research reviewed and approved the data linkage. We used the linked data to
      identify records for women aged 40-64 yr who were diagnosed with breast cancer
      between 2003 and 2007 and to extract information on insurance benefit type, care
      source, and cost to the MHS for breast cancer treatment. We estimated per capita
      costs for breast cancer care by benefit type and care source in 2008 USD using
      generalized linear models, adjusted for demographic, pathologic, and treatment
      characteristics. Results: The average per capita (n = 2,666) total cost for
      breast cancer care was $66,300 [standard error (SE) $9,200] over 3.31 (1.48)
      years of follow-up. Total costs were similar between benefit types, but varied by
      care source. The average per capita cost was $34,500 ($3,000) for direct care (n
      = 924), $96,800 ($4,800) for purchased care (n = 622), and $60,700 ($3,900) for
      both care sources (n = 1,120), respectively. Care source differences remained by
      tumor stage and for chemotherapy, radiation, and hormone therapy treatment types.
      Conclusions: Per capita costs to the MHS for breast cancer care were similar by
      benefit type and lower for direct care compared with purchased care. Further
      research is needed in breast and other tumor sites to determine patterns and
      determinants of cancer care costs between benefit types and care sources within
      the MHS.

PMID- 29660011
TI  - Craniotomy and Survival for Primary Central Nervous System Lymphoma.
AB  - BACKGROUND: Cytoreductive surgery is considered controversial for primary central
      nervous system lymphoma (PCNSL). OBJECTIVE: To investigate survival following
      craniotomy or biopsy for PCNSL. METHODS: The National Cancer Database-Participant
      User File (NCDB, n = 8936), Surveillance, Epidemiology, and End Results Program
      (SEER, n = 4636), and an institutional series (IS, n = 132) were used. We
      retrospectively investigated the relationship between craniotomy, prognostic
      factors, and survival for PCNSL using case-control design. RESULTS:  In NCDB,
      craniotomy was associated with increased median survival over biopsy (19.5 vs
      11.0 mo), independent of subsequent radiation and chemotherapy (hazard ratio [HR]
      0.80, P < .001). We found a similar trend with survival for craniotomy vs biopsy
      in the IS (HR 0.68, P = .15). In SEER, gross total resection was associated with
      increased median survival over biopsy (29 vs 10 mo, HR 0.68, P < .001). The
      survival benefit associated with craniotomy was greater within recursive
      partitioning analysis (RPA) class 1 group in NCDB (95.1 vs 29.1 mo, HR 0.66, P <
      .001), but was smaller for RPA 2-3 (14.9 vs 10.0 mo, HR 0.86, P < .001). A
      surgical risk category (RC) considering lesion location and number, age, and
      frailty was developed. Craniotomy was associated with increased survival vs
      biopsy for patients with low RC (133.4 vs 41.0 mo, HR 0.33, P = .01), but not
      high RC in the IS. CONCLUSION: Craniotomy is associated with increased survival
      over biopsy for PCNSL in 3 retrospective datasets. Prospective studies are
      necessary to adequately evaluate this relationship. Such studies should evaluate
      patients most likely to benefit from cytoreductive surgery, ie, those with
      favorable RPA and RC.

PMID- 29660013
TI  - Rethinking the Career Landscape for Nicotine and Tobacco Trainees and Early
      Career Professionals.

PMID- 29660012
TI  - Coordination of Rad1-Rad10 interactions with Msh2-Msh3, Saw1 and RPA is essential
      for functional 3' non-homologous tail removal.
AB  - Double strand DNA break repair (DSBR) comprises multiple pathways. A subset of
      DSBR pathways, including single strand annealing, involve intermediates with 3'
      non-homologous tails that must be removed to complete repair. In Saccharomyces
      cerevisiae, Rad1-Rad10 is the structure-specific endonuclease that cleaves the
      tails in 3' non-homologous tail removal (3' NHTR). Rad1-Rad10 is also an
      essential component of the nucleotide excision repair (NER) pathway. In both
      cases, Rad1-Rad10 requires protein partners for recruitment to the relevant DNA
      intermediate. Msh2-Msh3 and Saw1 recruit Rad1-Rad10 in 3' NHTR; Rad14 recruits
      Rad1-Rad10 in NER. We created two rad1 separation-of-function alleles,
      rad1R203A,K205A and rad1R218A; both are defective in 3' NHTR but functional in
      NER. In vitro, rad1R203A,K205A was impaired at multiple steps in 3' NHTR. The
      rad1R218A in vivo phenotype resembles that of msh2- or msh3-deleted cells;
      recruitment of rad1R218A-Rad10 to recombination intermediates is defective.
      Interactions among rad1R218A-Rad10 and Msh2-Msh3 and Saw1 are altered and
      rad1R218A-Rad10 interactions with RPA are compromised. We propose a model in
      which Rad1-Rad10 is recruited and positioned at the recombination intermediate
      through interactions, between Saw1 and DNA, Rad1-Rad10 and Msh2-Msh3, Saw1 and
      Msh2-Msh3 and Rad1-Rad10 and RPA. When any of these interactions is altered, 3'
      NHTR is impaired.

PMID- 29660014
TI  - IGF2BP1 enhances an aggressive tumor cell phenotype by impairing miRNA-directed
      downregulation of oncogenic factors.
AB  - The oncofetal IGF2 mRNA binding proteins (IGF2BPs) are upregulated in most
      cancers but their paralogue-specific roles in tumor cells remain poorly
      understood. In a panel of five cancer-derived cell lines, IGF2BP1 shows highly
      conserved oncogenic potential. Consistently, the deletion of IGF2BP1 impairs the
      growth and metastasis of ovarian cancer-derived cells in nude mice. Gene
      expression analyses in ovarian cancer-derived cells reveal that the knockdown of
      IGF2BPs is associated with the downregulation of mRNAs that are prone to miRNA
      regulation. All three IGF2BPs preferentially associate upstream of miRNA binding
      sites (MBSs) in the 3'UTR of mRNAs. The downregulation of mRNAs co-regulated by
      miRNAs and IGF2BP1 is abrogated at low miRNA abundance or when miRNAs are
      depleted. IGF2BP1 associates with these target mRNAs in RISC-free complexes and
      its deletion enhances their association with AGO2. The knockdown of most miRNA
      regulated target mRNAs of IGF2BP1 impairs tumor cell properties. In four primary
      cancers, elevated synthesis of these target mRNAs is largely associated with
      upregulated IGF2BP1 mRNA levels. In ovarian cancer, the enhanced expression of
      IGF2BP1 and most of its miRNA-controlled target mRNAs is associated with poor
      prognosis. In conclusion, these findings indicate that IGF2BP1 enhances an
      aggressive tumor cell phenotype by antagonizing miRNA-impaired gene expression.

PMID- 29660016
TI  - An Interview with Major General (Retired) Melissa Rank: The Evolution of Air
      Force Nurse Corps Leaders.

PMID- 29660015
TI  - Structural basis of DNA target recognition by the B3 domain of Arabidopsis
      epigenome reader VAL1.
AB  - Arabidopsis thaliana requires a prolonged period of cold exposure during winter
      to initiate flowering in a process termed vernalization. Exposure to cold induces
      epigenetic silencing of the FLOWERING LOCUS C (FLC) gene by Polycomb group (PcG)
      proteins. A key role in this epigenetic switch is played by transcriptional
      repressors VAL1 and VAL2, which specifically recognize Sph/RY DNA sequences
      within FLC via B3 DNA binding domains, and mediate recruitment of PcG silencing
      machinery. To understand the structural mechanism of site-specific DNA
      recognition by VAL1, we have solved the crystal structure of VAL1 B3 domain (VAL1
      B3) bound to a 12 bp oligoduplex containing the canonical Sph/RY DNA sequence 5'
      CATGCA-3'/5'-TGCATG-3'. We find that VAL1-B3 makes H-bonds and van der Waals
      contacts to DNA bases of all six positions of the canonical Sph/RY element. In
      agreement with the structure, in vitro DNA binding studies show that VAL1-B3 does
      not tolerate substitutions at any position of the 5'-TGCATG-3' sequence. The VAL1
      B3-DNA structure presented here provides a structural model for understanding the
      specificity of plant B3 domains interacting with the Sph/RY and other DNA
      sequences.

PMID- 29660018
TI  - Sexual Assault and Disabling PTSD in Active Duty Service Women.
AB  - Introduction: Sexual assault in the military is a major concern and may result in
      significant health problems, such as post-traumatic stress disorder (PTSD). Those
      developing disabling PTSD symptoms may require a disability evaluation. We
      examined disability evaluation trends for service women with PTSD to better
      understand characteristics associated with inability to continue Active Duty
      service. Methods: This is a retrospective review of disability reports and
      electronic medical records for 322 Active Duty women diagnosed with and treated
      for PTSD by psychiatrists and psychologists at a large military treatment
      facility between 2011 and 2014. Service women requiring medical disability
      evaluation for PTSD (n = 159) were included in the study as "IDES cases"
      (Integrated Disability Evaluation System - IDES). A similar number of women,
      randomly selected from those seeking care for PTSD but not requiring disability
      evaluation during the same period, were included in the "control" group (n =
      163). Analyzes done to evaluate differences between groups (IDES cases vs.
      controls) included demographic and service-related characteristics, history of
      chronic pain, and PTSD index trauma types, such as pre-military trauma and
      military sexual trauma (MST). Logistic regression was performed to identify the
      factors associated with inclusion in IDES. Results: MST was the most frequent
      PTSD index trauma in the IDES group (73.6% vs. 44.8% of control group) and the
      most significant factor associated with IDES inclusion (OR 2.6, p = 0.032). Those
      in the IDES group had significantly greater number of mental health visits for
      PTSD (IDES: m = 68.6 vs. controls: m = 29.6) and more frequent chronic pain
      history (IDES 40.9% vs. controls 19.6%) than those in the control group.
      Approximately 65% of women in both groups had a history of childhood abuse, but
      childhood abuse, as a PTSD index trauma, was negatively associated with IDES
      inclusion (OR 0.293, p = 0.006). Conclusions: Active Duty service women with PTSD
      and a MST index trauma are much more likely to require disability evaluation
      (IDES) than those with PTSD due to other trauma types. IDES evaluation for
      conditions such as PTSD may result in early termination of military service and
      is a potential downstream consequence of MST. Service women requiring greater
      numbers of mental health visits for PTSD treatment may benefit from a
      multidisciplinary approach to treating concurrent health conditions, such as
      chronic pain. Those providing care for service women should evaluate for MST,
      chronic pain and pre-military trauma, such as childhood abuse; and aggressively
      treat these conditions to prevent PTSD and disability.

PMID- 29660017
TI  - Defining the impact of sumoylation on substrate binding and catalysis by thymine
      DNA glycosylase.
AB  - Thymine DNA glycosylase (TDG) excises thymine from mutagenic G.T mispairs
      generated by deamination of 5-methylcytosine (mC) and it removes two mC
      derivatives, 5-formylcytosine (fC) and 5-carboxylcytosine (caC), in a multistep
      pathway for DNA demethylation. TDG is modified by small ubiquitin-like modifier
      (SUMO) proteins, but the impact of sumoylation on TDG activity is poorly defined
      and the functions of TDG sumoylation remain unclear. We determined the effect of
      TDG sumoylation, by SUMO-1 or SUMO-2, on substrate binding and catalytic
      parameters. Single turnover experiments reveal that sumoylation dramatically
      impairs TDG base-excision activity, such that G.T activity is reduced by >=45
      fold and fC and caC are excised slowly, with a reaction half-life of >=9 min (37
      degrees C). Fluorescence anisotropy studies reveal that unmodified TDG binds
      tightly to G.fC and G.caC substrates, with dissociation constants in the low
      nanomolar range. While sumoylation of TDG weakens substrate binding, the residual
      affinity is substantial and is comparable to that of biochemically-characterized
      readers of fC and caC. Our findings raise the possibility that sumoylation
      enables TDG to function, at least transiently, as reader of fC and caC. Notably,
      sumoylation could potentially facilitate TDG recruitment of other proteins,
      including transcription factors or epigenetic regulators, to these sites in DNA.

PMID- 29660019
TI  - Modeling the diffusion of D-2-hydroxyglutarate from IDH1 mutant gliomas in the
      central nervous system.
AB  - Background: Among diffusely infiltrative gliomas in adults, 20%-30% contain a
      point mutation in isocitrate dehydrogenase 1 (IDH1mut), which increases
      production of D-2-hydroxyglutarate (D2HG). This is so efficient that D2HG often
      reaches 30 mM within IDH1mut gliomas. Yet, while up to 100 uM D2HG can be
      detected in the circulating cerebrospinal fluid of IDH1mut glioma patients, the
      exposure of nonneoplastic cells within and surrounding an IDH1mut glioma to D2HG
      is unknown and difficult to measure directly. Methods: Conditioned medium from
      patient-derived wild type IDH1 (IDH1wt) and IDH1mut glioma cells was analyzed for
      D2HG by liquid chromatography-mass spectrometry (LC-MS). Mathematical models of
      D2HG release and diffusion around an IDH1mut glioma were independently generated
      based on fluid dynamics within the brain and on previously reported intratumoral
      and cerebrospinal D2HG concentrations. Results: LC-MS analysis indicates that
      patient-derived IDH1mut glioma cells release 3.7-97.0 pg D2HG per cell per week.
      Extrapolating this to an average-sized tumor (30 mL glioma volume and 1 * 108
      cells/mL tumor), the rate of D2HG release by an IDH1mut glioma (SA) is estimated
      at 3.2-83.0 * 10-12 mol/mL/sec. Mathematical models estimate an SA of 2.9-12.9 *
      10-12 mol/mL/sec, within the range of the in vitro LC-MS data. In even the most
      conservative of these models, the extracellular concentration of D2HG exceeds 3
      mM within a 2 cm radius from the center of an IDH1mut glioma. Conclusions: The
      microenvironment of an IDH1mut glioma is likely being exposed to high
      concentrations of D2HG, in the low millimolar range. This has implications for
      understanding how D2HG affects nonneoplastic cells in an IDH1mut glioma.

PMID- 29660020
TI  - Analysis of Anterior Cervical Discectomy and Fusion Healthcare Costs via the
      Value-Driven Outcomes Tool.
AB  - BACKGROUND: Examining the costs of single- and multilevel anterior cervical
      discectomy and fusion (ACDF) is important for the identification of cost drivers
      and potentially reducing patient costs. A novel tool at our institution provides
      direct costs for the identification of potential drivers. OBJECTIVE: To assess
      perioperative healthcare costs for patients undergoing an ACDF. METHODS: Patients
      who underwent an elective ACDF between July 2011 and January 2017 were identified
      retrospectively. Factors adding to total cost were placed into subcategories to
      identify the most significant contributors, and potential drivers of total cost
      were evaluated using a multivariable linear regression model. RESULTS: A total of
      465 patients (mean, age 53 +/- 12 yr, 54% male) met the inclusion criteria for
      this study. The distribution of total cost was broken down into supplies/implants
      (39%), facility utilization (37%), physician fees (14%), pharmacy (7%), imaging
      (2%), and laboratory studies (1%). A multivariable linear regression analysis
      showed that total cost was significantly affected by the number of levels
      operated on, operating room time, and length of stay. Costs also showed a narrow
      distribution with few outliers and did not vary significantly over time.
      CONCLUSION: These results suggest that facility utilization and supplies/implants
      are the predominant cost contributors, accounting for 76% of the total cost of
      ACDF procedures. Efforts at lowering costs within these categories should make
      the most impact on providing more cost-effective care.

PMID- 29660021
TI  - Mapping of genomic EGFRvIII deletions in glioblastoma: insight into rearrangement
      mechanisms and biomarker development.
AB  - Background: Epidermal growth factor receptor (EGFR) variant III (vIII) is the
      most common oncogenic rearrangement in glioblastoma (GBM), generated by deletion
      of exons 2 to 7 of EGFR. The proximal breakpoints occur in variable positions
      within the 123-kb intron 1, presenting significant challenges in terms of
      polymerase chain reaction (PCR)-based mapping. Molecular mechanisms underlying
      these deletions remain unclear. Methods: We determined the presence of EGFRvIII
      and its breakpoints for 29 GBM samples using quantitative PCR, arrayed PCR
      mapping, Sanger sequencing, and whole genome sequencing (WGS). Patient-specific
      breakpoint PCR was performed on tumors, plasma, and cerebrospinal fluid (CSF)
      samples. The breakpoint sequences and single nucleotide polymorphisms (SNPs) were
      analyzed to elucidate the underlying biogenic mechanism. Results: PCR mapping and
      WGS independently unveiled 8 EGFRvIII breakpoints in 6 tumors. Patient-specific
      primers yielded EGFRvIII PCR amplicons in matched tumors and in cell-free DNA
      (cfDNA) from a CSF sample, but not in cfDNA or extracellular-vesicle DNA from
      plasma. The breakpoint analysis revealed nucleotide insertions in 4 samples, an
      insertion of a region outside of the EGFR locus in 1, microhomologies in 3, as
      well as a duplication or an inversion accompanied by microhomologies in 2,
      suggestive of distinct DNA repair mechanisms. In the GBM samples that harbored
      distinct breakpoints, the SNP compositions of EGFRvIII and amplified non-vIII
      EGFR were identical, suggesting that these rearrangements arose from amplified
      non-vIII EGFR. Conclusion: Our approach efficiently "fingerprints" each sample's
      EGFRvIII breakpoints. Breakpoint sequence analyses suggest that independent
      breakpoints arose from precursor amplified non-vIII EGFR through different DNA
      repair mechanisms.

PMID- 29660022
TI  - Molecular ablation of tumor blood vessels inhibits therapeutic effects of
      radiation and bevacizumab.
AB  - Background: Glioblastoma (GBM) is an aggressive and highly vascular tumor with
      median survival below 2 years. Despite advances in surgery, radiotherapy, and
      chemotherapy, survival has improved modestly. To combat glioma vascular
      proliferation, anti-angiogenic agents targeting vascular endothelial growth
      factor (VEGF) were introduced. Preclinically these agents were effective, yet
      they did not improve overall survival in phase III trials. We tested the
      hypothesis that ganciclovir (GCV)-mediated killing of proliferating endothelial
      cells expressing herpes simplex virus type 1 thymidine kinase (HSV1-TK) would
      have direct antitumor effects, and whether vessel ablation would affect the
      antitumor activity of anti-VEGF antibodies and radiotherapy. Methods:
      Proliferating endothelial cells were eliminated using GCV-mediated killing of
      proliferating endothelial cells expressing HSV1-TK (in Tie2-TK-IRES-GFP mice).
      Syngeneic NRAS/p53 (NP) gliomas were implanted into the brains of Tie2-TK-IRES
      GFP mice. Endothelial proliferation activates the Tie2 promoter and HSV1-TK
      expression. Administration of GCV kills proliferating tumor endothelial cells and
      slows tumor growth. The effects of endothelial cell ablation on anti-angiogenic
      therapy were examined using anti-VEGF antibodies or irradiation. Results: GCV
      administration reduced tumor growth and vascular density, increased tumor
      apoptosis, and prolonged survival. Anti-VEGF antibodies or irradiation also
      prolonged survival. Surprisingly, combining GCV with irradiation, or with anti
      VEGF antibodies, reduced their individual therapeutic effects. Conclusion: GCV
      mediated killing of proliferating endothelial cells expressing HSV1-TK, anti-VEGF
      antibodies, or irradiation all reduced growth of a murine glioma. However,
      elimination of microvascular proliferation decreased the efficacy of anti-VEGF or
      irradiation therapy. We conclude that, in our model, the integrity of
      proliferating vessels is necessary for the antiglioma effects of anti-VEGF and
      radiation therapy.

PMID- 29660023
TI  - Radiation induces age-dependent deficits in cortical synaptic plasticity.
AB  - Background: Radiation-induced cognitive dysfunction is a significant side effect
      of cranial irradiation for brain tumors. Clinically, pediatric patients are more
      vulnerable than adults. However, the underlying mechanisms of dysfunction,
      including reasons for age dependence, are still largely unknown. Previous studies
      have focused on the loss of hippocampal neuronal precursor cells and deficits in
      memory. However, survivors may also experience deficits in attention, executive
      function, or other non-hippocampal-dependent cognitive domains. We hypothesized
      that brain irradiation induces age-dependent deficits in cortical synaptic
      plasticity. Methods: In vivo recordings were used to test neuronal plasticity
      along the direct pathway from the cornu ammonis 1 (CA1)/subicular region to the
      prefrontal cortex (PFC). Specifically, long-term potentiation (LTP) in the
      CA1/subicular-PFC pathway was assessed after cranial irradiation of juvenile and
      adult Sprague Dawley rats. We further assessed a potential role for glutamate
      toxicity by evaluating the potential neuroprotective effects of memantine.
      Results: LTP was greatly inhibited in both adult and juvenile animals at 3 days
      after radiation but returned to near-normal levels by 8 weeks-only in adult rats.
      Memantine given before, but not after, irradiation partially prevented LTP
      inhibition in juvenile and adult rats. Conclusion: Cranial radiation impairs
      neuroplasticity along the hippocampal-PFC pathway; however, its effects vary by
      age. Pretreatment with memantine offered protection to both juvenile and adult
      animals. Deficits in cortical plasticity may contribute to radiation-induced
      cognitive dysfunction, including deficits in attention and age-dependent
      sensitivity of such pathways, which may underlie differences in clinical outcomes
      between juveniles and adults after cranial irradiation.

PMID- 29660025
TI  - Morning Cortisol Is Associated With Stress and Sleep in Elite Military Men: A
      Brief Report.
AB  - Introduction: Accumulating evidence suggests that trends in salivary cortisol
      after awakening may be reliable biological predictors of morbidity and mortality.
      In a sample of elite military men, our lab recently established summary
      parameters of morning cortisol as well as their stability across 2 d of repeated
      sampling. Materials and Methods: In this follow-on study, we evaluated summary
      parameters and their relationships to theoretically relevant demographic (i.e.,
      age, body mass index) and biobehavioral correlates (i.e., blood pressure [BP],
      sleep parameters, fatigue, and perceived stress). Fifty-eight male active duty
      U.S. Navy SEALs self-collected salivary samples on 2 consecutive, midweek
      workdays upon waking (WAKE), WAKE+30 min, WAKE+60 min, 4 p.m., and 9 p.m. in a
      nondeployed, free-living setting. Resting BP was measured manually, and sleep
      wake periods were objectively derived using actigraphy. Daily fatigue and
      perceived stress were measured by self-report. Summary parameters of morning
      cortisol magnitude (i.e., peak value [Peak], area under the curve in terms of
      ground [AUCG], and average of morning samples [AVE]) were assessed with respect
      to each demographic and biobehavioral item via correlational analyses. A subgroup
      of 29 participants was selected for compliance with salivary sampling in the
      morning across 2 d. Results: Perceived stress was positively associated with Peak
      (r[27] = 0.437, p < 0.05), AUCG (r[25] = 0.500, p < 0.01), and AVE (r[25] =
      0.506, p < 0.01). Total sleep time was also positively associated with Peak
      (r[26] = 0.378, p < 0.05). There were borderline associations between some
      summary parameters and diastolic BP, percent sleep, and wake after sleep onset.
      Age, systolic BP, body mass index, time in bed, sleep efficiency, and fatigue did
      not associate with morning cortisol. Conclusions: Preliminary evidence of morning
      cortisol summary parameters as biobehavioral indicators was established, and
      these parameters appeared to associate with stress and sleep in elite military
      men.

PMID- 29660024
TI  - Crystal structure of the novel lesion-specific endonuclease PfuEndoQ from
      Pyrococcus furiosus.
AB  - Because base deaminations, which are promoted by high temperature, ionizing
      radiation, aerobic respiration and nitrosative stress, produce mutations during
      replication, deaminated bases must be repaired quickly to maintain genome
      integrity. Recently, we identified a novel lesion-specific endonuclease,
      PfuEndoQ, from Pyrococcus furiosus, and PfuEndoQ may be involved in the DNA
      repair pathway in Thermococcales of Archaea. PfuEndoQ recognizes a deaminated
      base and cleaves the phosphodiester bond 5' of the lesion site. To elucidate the
      structural basis of the substrate recognition and DNA cleavage mechanisms of
      PfuEndoQ, we determined the structure of PfuEndoQ using X-ray crystallography.
      The PfuEndoQ structure and the accompanying biochemical data suggest that
      PfuEndoQ recognizes a deaminated base using a highly conserved pocket adjacent to
      a Zn2+-binding site and hydrolyses a phosphodiester bond using two Zn2+ ions. The
      PfuEndoQ-DNA complex is stabilized by a Zn-binding domain and a C-terminal
      helical domain, and the complex may recruit downstream proteins in the DNA repair
      pathway.

PMID- 29660026
TI  - Familial Syndromes Involving Meningiomas Provide Mechanistic Insight Into
      Sporadic Disease.
AB  - Currently, there is an incomplete understanding of the molecular pathogenesis of
      meningiomas, the most common primary brain tumor. Several familial syndromes are
      characterized by increased meningioma risk, and the genetics of these syndromes
      provides mechanistic insight into sporadic disease. The best defined of these
      syndromes is neurofibromatosis type 2, which is caused by a mutation in the NF2
      gene and has a meningioma incidence of approximately 50%. This finding led to the
      subsequent discovery that NF2 loss-of-function occurs in up to 60% of sporadic
      tumors. Other important familial diseases with increased meningioma risk include
      nevoid basal cell carcinoma syndrome, multiple endocrine neoplasia 1 (MEN1),
      Cowden syndrome, Werner syndrome, BAP1 tumor predisposition syndrome, Rubinstein
      Taybi syndrome, and familial meningiomatosis caused by germline mutations in the
      SMARCB1 and SMARCE1 genes. For each of these syndromes, the diagnostic criteria,
      incidence in the population, and frequency of meningioma are presented to review
      the relevant clinical information for these conditions. The genetic mutations,
      molecular pathway derangements, and relationship to sporadic disease for each
      syndrome are described in detail to identify targets for further investigation.
      Familial syndromes characterized by meningiomas often affect genes and pathways
      that are also implicated in a subset of sporadic cases, suggesting key molecular
      targets for therapeutic intervention. Further studies are needed to resolve the
      functional relevance of specific genes whose significance in sporadic disease
      remains to be elucidated.

PMID- 29660027
TI  - The 6-hydroxychromanol derivative SUL-109 ameliorates renal injury after deep
      hypothermia and rewarming in rats.
AB  - Background: Mitochondrial dysfunction plays an important role in kidney damage in
      various pathologies, including acute and chronic kidney injury and diabetic
      nephropathy. In addition to the well-studied ischaemia/reperfusion (I/R) injury,
      hypothermia/rewarming (H/R) also inflicts acute kidney injury. Substituted 6
      hydroxychromanols are a novel class of mitochondrial medicines that ameliorate
      mitochondrial oxidative stress and protect the mitochondrial network. To identify
      a novel 6-hydroxychromanol that protects mitochondrial structure and function in
      the kidney during H/R, we screened multiple compounds in vitro and subsequently
      assessed the efficacy of the 6-hydroxychromanol derivatives SUL-109 and SUL-121
      in vivo to protect against kidney injury after H/R in rats. Methods: Human
      proximal tubule cell viability was assessed following exposure to H/R for 48/4 h
      in the presence of various 6-hydroxychromanols. Selected compounds (SUL-109, SUL
      121) or vehicle were administered to ketamine-anaesthetized male Wistar rats (IV
      135 ug/kg/h) undergoing H/R at 15 degrees C for 3 h followed by rewarming and
      normothermia for 1 h. Metabolic parameters and body temperature were measured
      throughout. In addition, renal function, renal injury, histopathology and
      mitochondrial fitness were assessed. Results: H/R injury in vitro lowered cell
      viability by 94 +/- 1%, which was counteracted dose-dependently by multiple 6
      hydroxychomanols derivatives. In vivo, H/R in rats showed kidney injury molecule
      1 expression in the kidney and tubular dilation, accompanied by double-strand DNA
      breaks and protein nitrosylation. SUL-109 and SUL-121 ameliorated tubular kidney
      damage, preserved mitochondrial mass and maintained cortical adenosine 5'
      triphosphate (ATP) levels, although SUL-121 did not reduce protein nitrosylation.
      Conclusions: The substituted 6-hydroxychromanols SUL-109 and SUL-121 ameliorate
      kidney injury during in vivo H/R by preserving mitochondrial mass, function and
      ATP levels. In addition, both 6-hydroxychromanols limit DNA damage, but only SUL
      109 also prevented protein nitrosylation in tubular cells. Therefore SUL-109
      offers a promising therapeutic strategy to preserve kidney mitochondrial
      function.

PMID- 29660028
TI  - Reoperation for Medulloblastoma Prior to Adjuvant Therapy.
AB  - BACKGROUND: Surgery remains an integral part of the treatment of medulloblastoma.
      We present our experience with repeat surgery for this tumor before initiation of
      adjuvant therapy. OBJECTIVE: To report what was found intraoperatively and where
      at time of second-look surgery and detail any postoperative events or
      readmissions within 90 days of surgery. METHODS: Two separate institutional
      databases were queried to identify patients who underwent repeat resection of
      suspected residual medulloblastoma from January 2003 to January 2017. RESULTS: We
      identified 51 patients (36 male, 15 female) who underwent repeat surgery. Average
      age at diagnosis was 8.31 years (range, 1.3-21.2). Imaging prior to repeat
      surgery demonstrated unequivocal residual tumor in 37 patients, but indeterminate
      in 14 patients. All but 1 patient had histopathologically confirmed residual
      tumor (50/51, 98%). The fourth ventricle was the primary site in 39 (76%) cases,
      compared with hemispheric in 12 cases (24%). Thirty (59%) tumors were non-WNT/non
      SHH. All indeterminate cases (except for 1 patient) had residual tumor.
      Hemostatic agents were found within the resection cavity in 80% of indeterminate
      cases. The most common sites of residual tumor were lateral (26/39, 67%, lateral
      recess and/or foramen of Luschka) and roof (25/39, 64%); the superior medullary
      velum was the most common region of the roof (19/25, 76%). Eight (16%) patients
      developed new neurological deficits: cranial nerve palsies in 5 patients and
      posterior fossa syndrome in 3 patients. CONCLUSION: Meticulous inspection of the
      resection cavity is necessary, paying particular attention to the roof and
      lateral recess. Hemostatic agents can conceal residual tumor.

PMID- 29660029
TI  - Chloride: from Nutrient to Toxicant.
AB  - In salinized soils in which chloride (Cl-) is the dominant salt anion, growth of
      plants that tolerate only low concentrations of salt (glycophytes) is disturbed
      by Cl- toxicity. Chlorotic discolorations precede necrotic lesions, causing yield
      reductions. Little is known about the effects of Cl- toxicity on these
      dysfunctions. A lack of understanding exists regarding (i) the molecular and
      physiological mechanisms that lead to Cl--induced damage and (ii) the adaptive
      aspects of induced tolerance to Cl- salinity. Here, mechanistic explanations for
      the Cl--induced stress responses are proposed and novel ideas and strategies by
      which glycophytic plants avoid the excessive accumulation of Cl- are reviewed.
      New experiments are suggested to test the proposed hypotheses. Cl- salinity
      constrains global food security and thus we urgently need more research into the
      causes and consequences of Cl- salinity.

PMID- 29660030
TI  - Letter: Angio-Architectural Features of High-Grade Intracranial Dural
      Arteriovenous Fistulas: Correlation With Aggressive Clinical Presentation and
      Hemorrhagic Risk.

PMID- 29660031
TI  - Meningioma transcription factors link cell lineage with systemic metabolic cues.
AB  - Background: Tumor cells recapitulate cell-lineage transcriptional programs that
      are characteristic of normal tissues from which they arise. It is unclear why
      such lineage programs are fatefully maintained in tumors and if they contribute
      to cell proliferation and viability. Methods: Here, we used the most common brain
      tumor, meningioma, which is strongly associated with female sex and high body
      mass index (BMI), as a model system to address these questions. We screened
      expression profiling data to identify the transcription factor (TF) genes which
      are highly enriched in meningioma, and characterized the expression pattern of
      those TFs and downstream genes in clinical meningioma samples as well as normal
      brain tissues. Meningioma patient-derived cell lines (PDCLs) were used for
      further validation and characterization. Results: We identified 8 TFs highly
      enriched in meningioma. Expression of these TFs, which included sine oculis
      homeobox 1 (SIX1), readily distinguished meningiomas from other primary brain
      tumors and was maintained in PDCLs and even in pulmonary meningothelial nodules.
      In meningioma PDCLs, SIX1 and its coactivator eyes absent 2 (EYA2) supported the
      expression of the leptin receptor (LEPR), the cell-surface receptor for leptin
      (LEP), the adipose-specific hormone that is high in women and in individuals with
      high BMI. Notably, these transcriptional regulatory factors, LEPR and LEP, both
      contributed to support meningioma PDCLs proliferation and survival, elucidating a
      survival dependency on both a core transcriptional program and a metabolic cell
      surface receptor. Conclusions: These findings provide one rationale for why
      lineage TF expression is maintained in meningioma and for the epidemiological
      association of female sex and obesity with meningioma risk.

PMID- 29660032
TI  - FCTC Implementation in Nigeria: Lessons for Low and Middle-Income Countries.
AB  - Background: Nigeria is a significant tobacco market and influential country in
      Africa. Nigeria ratified the WHO Framework Convention on Tobacco Control (FCTC)
      in 2005. We reviewed Nigeria's tobacco control legislation since 2000 and
      compliance of the National Tobacco Control Act (NTCA) 2015 with the FCTC.
      Methods: We reviewed the National Tobacco Control Bills 2011 (proposed by
      legislature) and 2014 (proposed by Executive), the NTCA 2015, and media stories
      on tobacco control from 2008 to 2017. Results: The NTCA, despite being more
      comprehensive than Nigeria's first Tobacco Smoking (Control) law of 1990,
      maintained provisions promoted by the tobacco industry. Examples include:
      allowing designated smoking areas in hospitality venues, higher educational
      institutions, and transportation venues; a loophole in the advertising
      restictions allowing communications with consenting adults; having the
      Manufacturers Association of Nigeria (MAN) (which includes tobacco companies) on
      the National Tobacco Control Committee charged with working with the Ministry of
      Health to implement the law. The industry is also directly involved with the
      Standards Organisation of Nigeria (SON) in preparing regulations on cigarette
      constituents and emissions. In an unprecedented step globally, the law requires
      that implementing regulations be approved by the National Assembly, giving the
      industry another opportunity to weaken this law further by lobbying the
      legislators to favour the industry. As of January 2018 the law was still not
      being enforced. Conclusion: The NTCA can be strengthened through implementation
      guidelines still being developed. The industry should be prevented from
      interfering with through MAN and SON, as required by FCTC Article 5.3.
      Implications: The tobacco industry works to block FCTC implementation even after
      a country ratifies the treaty. The Nigerian case illustrates that it is essential
      for health authorities to remain vigilant and ensure that the tobacco industry
      does not play a decision-making role in the process of tobacco legislation and
      regulation either directly or indirectly. The unprecedented step of requiring
      approval of implementing regulations for the Nigerian law should not be allowed
      to become a precedent in other countries.

PMID- 29660034
TI  - E-cigarettes May Support Smokers With High Smoking-Related Risk Awareness to Stop
      Smoking in the Short Run: Preliminary Results by Randomized Controlled Trial.
AB  - Introduction: E-cigarettes may be positively used in tobacco cessation
      treatments. However, neither the World Health Organization nor the American Food
      and Drug Administration has recognized them as effective cessation aids. Data
      about the efficacy and safety of e-cigarettes are still limited and
      controversial. Methods: This was a double-blind randomized controlled study. The
      main aim was to assess the efficacy of the use of e-cigarettes in a tobacco
      cessation program with a group of chronic smokers voluntarily involved in long
      term lung cancer screening. Participants were randomized into three arms: e
      cigarettes (Arm 1), placebo (Arm 2), and control (Arm 3). All subjects also
      received a low-intensity counseling. Results: About 25% of participants who
      followed a cessation program based on the use of e-cigarettes (Arm 1 and Arm 2)
      were abstinent after 3 months. Conversely, only about 10% of smokers in Arm 3
      stopped. Participants in Arm 1 also reported a higher reduction rate (M = 
      11.6441, SD = 7.574) than participants in Arm 2 (M = -10.7636, SD = 8.156) and
      Arm 3 (M = -9.1379, SD = 8.8127). Conclusions: Our findings support the efficacy
      and safety of e-cigarettes in a short-term period. E-cigarettes use led to a
      higher cessation rate. Furthermore, although all participants reported a
      significant reduction of daily cigarette consumption compared to the baseline,
      the use of e-cigarettes (including those without nicotine) allowed smokers to
      achieve better results. Implications: E-cigarettes increased the stopping rate as
      well as the reduction of daily cigarettes in participants who continued smoking.
      In fact, although all participants reported a significant reduction of tobacco
      consumption compared to the baseline, the use of e-cigarettes allowed smokers to
      achieve a better result. It could be worthwhile to associate this device with new
      ICT-driven models of self-management support in order to enable people to better
      handle behavioral changes and side effects. This is true for ready-to-quit
      smokers (such as our participants) but can also be advantageous for less
      motivated smokers engaged in clinical settings.

PMID- 29660033
TI  - Phosphorylation of xeroderma pigmentosum group C regulates ultraviolet-induced
      DNA damage repair.
AB  - Nucleotide excision repair (NER) is the most versatile DNA repair system that
      removes bulky DNA damage induced by various endogenous and exogenous factors,
      including UV radiation. Defects in NER can lead to the xeroderma pigmentosum (XP)
      syndrome, mainly characterized by increased carcinogenesis in the skin. The
      function of NER factors, including xeroderma pigmentosum group C (XPC), can be
      regulated by post-translational modifications such as ubiquitination. However,
      the role of phosphorylation in XPC function remains unknown. Here, we show that
      phosphorylation of XPC acts as a novel post-translational regulatory mechanism of
      the NER pathway. We show that XPC is phosphorylated at serine 94. Moreover, after
      UVB irradiation, XPC phosphorylation regulates recruitment of ubiquitinated XPC
      and its downstream NER factors to the chromatin. In addition, upon evaluating the
      predicted kinases for XPC phosphorylation, we found that casein kinase II (CK2)
      promotes NER. Furthermore, CK2 kinase mediates XPC phosphorylation at serine 94,
      and also promotes recruitment of ubiquitinated XPC to the chromatin after UVB
      irradiation. Our findings have identified XPC phosphorylation as a new mechanism
      for regulating NER following UV-induced DNA damage.

PMID- 29660035
TI  - The preventable burden of work-related ill-health.
AB  - Background: The fraction of ill-health overall attributable to occupational
      conditions has not been extensively evaluated, thus contributing to the
      perception of a lesser relevance of education and research in occupational health
      in respect to other fields of medical research and practice. Aims: To assess the
      relevance of work-related conditions on the aetiology of human ill-health in
      different health domains. Methods: We extracted the risk estimates associated
      with heritability and with occupational risk factors for chronic lymphocytic
      leukaemia (CLL), major depressive disorder (MDD) and long QT syndrome (LQTS) from
      13 published international reports. The selection criteria for the eligible
      studies were: genome-wide studies, or studies of the occupational risk factors
      associated with one of the three diseases of interest. We calculated and compared
      the respective population attributable fraction for the combined occupational
      risk factors, and for heritability. Results: We estimated that occupational risk
      factors would account for 12% (95% confidence interval (CI) 4-19) of CLL, 11%
      (95% CI 7-15) of MDD and 10% (95% CI 2-13) of LQTS burden in the general
      population. The corresponding figures for heritability would be 16% (95% CI 11
      22), 28% (95% CI 20-5) and 17% (95% CI 7-27). Conclusions: More efforts in
      capacity building and research in occupational health are warranted aiming to
      prevent ill-health and to preserve a productive life for the ageing work
      population.

PMID- 29660036
TI  - Exercise therapy and work-related musculoskeletal disorders in sedentary workers.
AB  - Background: Work-related upper limb disorders (WRULDs) are a syndrome of symptoms
      affecting the upper quadrant of the body and are a significant cause of pain,
      disability and sickness absence among workers. Exercise therapy is considered to
      be a clinical and cost-effective strategy in WRULD management. Aims: To evaluate
      the effectiveness of exercise therapy for WRULDs in sedentary workers. Methods:
      This review follows an a priori protocol to maintain internal validity describing
      essential procedures to be followed (e.g. a comprehensive search strategy, duel
      extraction and critical appraisal). The methodological quality of the studies
      were assessed using Cochrane Risk of Bias Tool for all randomized controlled
      trials and the Assessing the Methodological Quality of Systematic Reviews
      (AMSTAR) tool for systematic reviews. Results: A total of 11 articles were
      selected for inclusion. There was moderate evidence to suggest exercise is
      effective in reducing the symptoms of pain and improved function in WRULDs in
      sedentary workers when compared to a control group. Conclusions: The results were
      comparable to recent systematic reviews, which have found evidence to support the
      use of exercise therapy, in mixed populations of workers. There is a need for
      further research to highlight the most effective form of exercise, optimal dosage
      and delivery method.

PMID- 29660037
TI  - Twelve Million Smokers Look Online for Smoking Cessation Help Annually: Health
      Information National Trends Survey Data, 2005-2017.
AB  - Background: This study quantified the potential reach of Internet smoking
      cessation interventions to support calculations of potential population impact
      (reach * effectiveness). Using a nationally representative survey, we calculated
      the number and proportion of adult smokers that look for cessation assistance
      online each year. Methods: Five waves (2005, 2011, 2013, 2015, 2017) of the
      National Cancer Institute's Health Information National Trends Survey were
      examined. The survey asked US adults whether they ever go online to use the
      Internet, World Wide Web, or email and had used the Internet to look for
      information about quitting smoking within the past 12 months. We estimated the
      proportion and number of (1) all US adult smokers, and (2) online US adult
      smokers that searched for cessation information online. Cross-year comparisons
      were assessed with logistic regression. Results: The proportion of all smokers
      who searched online for cessation information increased over the past decade (p <
      .001): 16.5% in 2005 (95% CI = 13.2% to 20.4%), 20.9% in 2011 (95% CI = 15.55% to
      28.0%), 25.6% in 2013 (95% CI = 19.7% to 33.0%), 23.4% in 2015 (95% CI = 16.9% to
      31.0%), and 35.9% in 2017 (95% CI = 24.8% to 48.9%). Among online smokers only,
      approximately one third searched online for cessation information each year from
      2005 through 2015. In 2017, that proportion increased to 43.7% (95% CI = 29.7% to
      58.7%), when an estimated 12.4 million online smokers searched for cessation
      help. Conclusions: More than one third of all smokers turn to the Internet for
      help quitting each year, representing more than 12 million US adults.
      Implications: This research provides contemporary estimates for the reach of
      Internet interventions for smoking cessation. Such estimates are necessary to
      estimate the population impact of Internet interventions on quit rates. The
      research finds more than 12 million US smokers searched online for cessation
      information in 2017.

PMID- 29660038
TI  - External Ventricular Drain and Hemorrhage in Aneurysmal Subarachnoid Hemorrhage
      Patients on Dual Antiplatelet Therapy: A Retrospective Cohort Study.
AB  - BACKGROUND: Stenting and flow diversion for aneurysmal sub arachnoid hemorrhage
      (aSAH) require the use of dual antiplatelet therapy (DAPT). OBJECTIVE: To
      investigate whether DAPT is associated with hemorrhagic complication following
      placement of external ventricular drains (EVD) in patients with aSAH. METHODS:
      Rates of radiographically identified hemorrhage associated with EVD placement
      were compared between patients who received DAPT for stenting or flow diversion,
      and patients who underwent microsurgical clipping or coiling and did not receive
      DAPT by way of a backward stepwise multivariate analysis. RESULTS: Four hundred
      forty-three patients were admitted for aSAH management. Two hundred ninety-eight
      patients required placement of an EVD. One hundred twenty patients (40%) were
      treated with stent-assisted coiling or flow diversion and required DAPT, while
      178 patients (60%) were treated with coiling without stents or microsurgical
      clipping and did not receive DAPT. Forty-two (14%) cases of new hemorrhage along
      the EVD catheter were identified radiographically. Thirty-two of these
      hemorrhages occurred in patients on DAPT, while 10 occurred in patients without
      DAPT. After multivariate analysis, DAPT was significantly associated with
      radiographic hemorrhage [odds ratio: 4.92, 95% confidence interval: 2.45-9.91, P
      = .0001]. We did not observe an increased proportion of symptomatic hemorrhage in
      patients receiving DAPT (10 of 32 [31%]) vs those without (5 of 10 [50%]; P =
      .4508). CONCLUSION: Patients with aSAH who receive stent-assisted coiling or flow
      diversion are at higher risk for radiographic hemorrhage associated with EVD
      placement. The timing between EVD placement and DAPT initiation does not appear
      to be of clinical significance. Stenting and flow diversion remain viable options
      for aSAH patients.

PMID- 29660039
TI  - Trial Readiness in Cavernous Angiomas With Symptomatic Hemorrhage (CASH).
AB  - BACKGROUND: Brain cavernous angiomas with symptomatic hemorrhage (CASH) are
      uncommon but exact a heavy burden of neurological disability from recurrent
      bleeding, for which there is no proven therapy. Candidate drugs to stabilize the
      CASH lesion and prevent rebleeding will ultimately require testing of safety and
      efficacy in multisite clinical trials. Much progress has been made in
      understanding the epidemiology of CASH, and novel biomarkers have been linked to
      the biological mechanisms and clinical activity in lesions. Yet, the ability to
      enroll and risk-stratify CASH subjects has never been assessed prospectively at
      multiple sites. Biomarkers and other outcomes have not been evaluated for their
      sensitivity and reliability, nor have they been harmonized across sites.
      OBJECTIVE: To address knowledge gaps and establish a research network as
      infrastructure for future clinical trials, through the Trial Readiness grant
      mechanism, funded by National Institute of Neurological Disorders and
      Stroke/National Institutes of Health. METHODS: This project includes an
      observational cohort study to assess (1) the feasibility of screening, enrollment
      rates, baseline disease categorization, and follow-up of CASH using common data
      elements at multiple sites, (2) the reliability of imaging biomarkers including
      quantitative susceptibility mapping and permeability measures that have been
      shown to correlate with lesion activity, and (3) the rates of recurrent
      hemorrhage and change in functional status and biomarker measurements during
      prospective follow-up. EXPECTED OUTCOMES: We propose a harmonized multisite
      assessment of enrollment rates of CASH, baseline features relevant to
      stratification in clinical trials, and follow-up assessments of functional
      outcomes in relation to clinical bleeds. We introduce novel biomarkers of
      vascular leak and hemorrhage, with firm mechanistic foundations, which have been
      linked to clinical disease activity. We shall test their reliability and validity
      at multiple sites, and assess their changes over time, with and without clinical
      rebleeds, hence their fitness as outcome instruments in clinical trials.
      DISCUSSION: The timing cannot be more opportune, with therapeutic targets
      identified, exceptional collaboration among researchers and the patient
      community, along with several drugs ready to benefit from development of a path
      to clinical testing using this network in the next 5 years.

PMID- 29660040
TI  - Commentary: La Pitie-Salpetriere Hospital in Paris: the Historic Cradle of
      Neurosurgery.

PMID- 29660041
TI  - Cardiovascular Effects of Hookah Smoking: Potential Implications for
      Cardiovascular Risk.
AB  - Implications: This review provides an overview on the potential impact of hookah
      smoking on cardiovascular health. Readers will gain an insight into evidence on
      its toxicological constituents, human health effects, and pathophysiological
      mechanisms by which hookah smoking might cause cardiovascular disease. The review
      also highlights current research gaps regarding the cardiovascular consequences
      of hookah smoking, specifically the long-term consequences in the U.S. and Europe
      among flavored hookah tobacco users.

PMID- 29660042
TI  - Pediatric Irritable Bowel Syndrome: Perspectives on Pain and Adolescent Social
      Functioning.
AB  - Objective: The goal of the study was to describe the experiences of adolescents
      with irritable bowel syndrome (IBS) from the perspective of adolescents, their
      parents, and health care providers who treat adolescents who have IBS. Design:
      The study consisted of semistructured interviews. Setting: Participants were
      recruited from multidisciplinary pain clinics. Subjects: Thirty-six people
      participated in the study: 12 adolescents, 12 parents, and 12 health care
      providers. Results: Two main themes associated with the impact of IBS on
      adolescents' social functioning emerged from the qualitative interview data: 1)
      disconnection from peers and 2) strain on family relationships, with subthemes
      reflecting the perspectives of adolescents, parents, and health care providers.
      Conclusions: Participants in our study described that adolescents with IBS
      encounter significant peer- and family-related social stress. Helpful
      interventions may be those that focus on social support from other adolescents
      with similar conditions, as well as family-based therapeutic interventions.

PMID- 29660043
TI  - Delayed Occipitocervical Instability With Cranial Settling After Far-Lateral
      Transcondylar Surgery for Invasive Skull Base Tumor.
AB  - BACKGROUND: Occipitocervical instability is a rare but potentially severe
      complication of a far-lateral transcondylar surgical approach to the skull base.
      OBJECTIVE: To investigate the incidence of clinically significant
      occipitocervical instability after transcondylar surgery via a far-lateral
      approach and to determine whether the extent of occipital condyle resection
      relative to the hypoglossal canal was associated with the development of
      occipitocervical instability. METHODS: A retrospective review of patients
      undergoing far-lateral transcondylar surgery was performed at our institution to
      identify patients who developed postoperative occipitocervical instability.
      RESULTS: Of the 61 far-lateral transcondylar operations performed, the authors
      identified 2 cases of delayed occipitocervical instability after surgery. In each
      case, the patient had tumor invading into the occipital condyle and supracondylar
      region and a resection extending anterior to the hypoglossal canal was performed.
      Both patients presented with pathological fractures and a severe occipitocervical
      deformity. CONCLUSION: Patients who have tumor involvement of the occipital
      condyle and supracondylar region and undergo partial unilateral condylar
      resection are at risk for occipitocervical instability and should be considered
      for occipitocervical fusion.

PMID- 29660044
TI  - Multimodal Neuroimaging Differences in Nicotine Abstinent vs. Satiated Smokers.
AB  - Introduction: Research on cigarette smokers suggests cognitive and behavioral
      impairments. However, much remains unclear how the functional neurobiology of
      smokers is influenced by nicotine state. Therefore, we sought to determine which
      state, be it acute nicotine abstinence or satiety, would yield the most robust
      differences compared to non-smokers when assessing neurobiological markers of
      nicotine dependence. Methods: Smokers(N=15) and sociodemographically matched non
      smokers(N=15) were scanned twice using a repeated-measures design. Smokers were
      scanned after a 24-hour nicotine abstinence, and immediately after smoking their
      usual brand cigarette. The neuroimaging battery included a stop-signal task of
      response inhibition and pseudo-continuous arterial spin labeling to measure
      cerebral blood flow (CBF). Whole brain voxel-wise ANCOVAs were carried out on
      stop success and stop fail SST contrasts and CBF maps to assess differences among
      non-, abstinent and satiated smokers. Cluster-correction was performed using
      AFNI's 3dClustSim to achieve a significance of p<0.05. Results: Smokers exhibited
      higher brain activation in bilateral inferior frontal gyrus (IFG), a brain region
      known to be involved in inhibitory control, during successful response
      inhibitions relative to non-smokers. This effect was significantly higher during
      nicotine abstinence relative to satiety. Smokers also exhibited lower CBF in the
      bilateral IFG than non-smokers. These hypo-perfusions were not different between
      abstinence and satiety. Conclusions: These findings converge on alterations in
      smokers in prefrontal circuits known to be critical for inhibitory control. These
      effects are present, even when smokers are satiated, but the neural activity
      required to achieve performance equal to controls is increased when smokers are
      in acute abstinence. Implications: Our multi-modal neuroimaging study gives
      neurobiological insights into the cognitive demands of maintaining abstinence and
      suggest targets for assessing the efficacy of therapeutic interventions.

PMID- 29660045
TI  - Effect of dietary supplementation with Moringa oleifera leaf on performance, meat
      quality, and oxidative stability of meat in broilers.
AB  - The objective of this study was to evaluate the effects of dietary
      supplementation with Moringa oleifera leaf (MOL) on performance, carcass
      characteristics, meat quality, and oxidative stability of breast muscle in
      broilers. A total of 720 1-d-old male Arbor Acres birds were randomly divided
      into 6 dietary groups, which were fed a basal diet supplemented with 0, 1, 2, 5,
      10, and 15% MOL, respectively. Each group had 6 replicates of 20 birds each. The
      feeding trial lasted for 42 d. The results showed dietary MOL supplementation
      linearly and quadratically decreased body weight and average daily gain (P <
      0.01), and increased feed conversion ratio (P < 0.001). Abdominal fat decreased
      linearly and quadratically in response to the supplementation of MOL in diets,
      both on d 21 and 42 (P < 0.001). In breast muscle, dietary supplementation with
      MOL quadratically increased the contents of C18:2, C18:3n-3, C20:4,
      polyunsaturated fatty acids (PUFA), n-3 PUFA, n-6 PUFA (P < 0.01), and decreased
      thrombogenic index (TI; P = 0.019). Dietary inclusion of MOL improved meat color,
      evidenced by quadratically reduced b* (yellowness) values (45 min postmortem, P =
      0.001; 24 h postmortem, P = 0.018) and increased a* (redness) values (24 h
      postmortem, P < 0.001). Besides, diets supplemented with MOL quadratically
      decreased malondialdehyde (MDA) levels in breast muscle during storage (P <
      0.001). Plasma total anti-oxidative capacity, total superoxide dismutase,
      glutathione peroxidase activities increased quadratically (P < 0.01), whereas MDA
      decreased quadratically (P < 0.001), in response to dietary MOL supplementation.
      In summary, MOL could be used as a feed ingredient for broilers to improve PUFA
      contents, oxidative stability, color of breast muscle, and abdominal fat without
      adverse effects on growth performance, with an inclusion of 1.56% in the diets.

PMID- 29660046
TI  - Seeing new opportunities to help smokers quit: A UK national survey of
      optometrist delivered smoking cessation behavioural support interventions.
AB  - Background: Smoking is a risk factor for various eye conditions. Brief smoking
      cessation interventions have demonstrated effectiveness when delivered by a range
      of healthcare professionals. Optometrists are well-placed in the community to
      advise otherwise healthy smokers to quit, yet remain relatively neglected in
      smoking cessation research and policy. In a national survey, this study
      investigated self-reported practices of UK optometrists for delivering brief
      tobacco smoking cessation interventions to patients. Methods: A randomly selected
      sample of 1,200 optometrists out of the 9000 optometrists registered on the UK
      College of Optometrists database were invited to complete a 40-item, web-based
      survey assessing: training related to smoking cessation; current practice [i.e.
      the proportion of patients to which components of very brief advice (Ask, Advise,
      Assist) and other evidence-based smoking cessation behaviour change techniques
      were delivered]; and barriers/enablers to intervention delivery. Results: In
      total, 408 (34%) responses were received. Most (83%) optometrists received no
      training in practical skills for delivering smoking cessation support. A third
      (34%) routinely assessed smoking status. Fewer self-reported advising smokers to
      quit (22%), offering assistance (via referral to dedicated services) (3%), or
      advice on smoking cessation medications (2%). Perceived barriers included
      insufficient knowledge/training (81%) and time (65%). Optometrists were more
      likely to assess and advise on smoking cessation if they practised in Scotland
      (chi2(2)=32.95,  p<0.001), an independent optometry practice (chi2(1)=4.27, 
      p=0.39), or had received smoking cessation training chi2(1)=13.1,  p<0.001).
      Conclusions: Substantial gaps exist in UK optometrists' current smoking cessation
      training and practice. Evidence-based training resources are needed to support
      the implementation of smoking cessation interventions into routine optometry
      practice. Implications: Optometrists are well placed in the community to delivery
      brief advice interventions to a large population of smokers. This survey provides
      a comprehensive description of current UK optometry practice related to the
      provision of evidence-based brief tobacco smoking cessation interventions to
      patients. Although optometrists perceive advising on smoking cessation as part of
      their role, numerous substantial gaps in current practice and training remain
      which need to be addressed through targeted interventions to increase
      implementation.

PMID- 29660048
TI  - FDA Policy on Setting Maximum Nicotine Content in Cigarettes.

PMID- 29660047
TI  - Trigeminal Nerve Atrophy Predicts Pain Recurrence After Gamma Knife Stereotactic
      Radiosurgery for Classical Trigeminal Neuralgia.
AB  - BACKGROUND: Trigeminal nerve atrophy and neurovascular compression (NVC) are
      frequently observed in classical trigeminal neuralgia (CTN). OBJECTIVE: To
      determine whether nerve characteristics contribute to Gamma Knife (Elekta AB,
      Stockholm, Sweden) surgery (GKS) outcomes in unilateral CTN without previous
      surgery. METHODS: From 2006 to 2012, 67 patients with unilateral CTN without
      previous surgery received GKS with a maximal dose of 90 Gy delivered to the
      trigeminal nerve juxta brainstem. Two evaluators, blinded to the side of pain,
      analyzed the magnetic resonance images before GKS to obtain the parameters,
      including nerve cross-sectional area (CSA), vessel type of NVC, and site of NVC
      along the nerve. Correlations of the parameters with pain relief (Barrow
      Neurological Institute [BNI] grades I-IIIb) and recurrence (BNI grades VI-V) were
      made by using Cox regression and Kaplan-Meier analyses. RESULTS: The median CSA
      of the symptomatic nerves was significantly smaller than that of the asymptomatic
      nerves (4.95 vs 5.9 mm2, P < .001). After adjustment for age and sex, larger
      nerve CSA was associated with lower initial pain relief (hazard ratio 0.81, P =
      .03) and lower pain recurrence after initial response (hazard ratio 0.58, P =
      .02). Patients with nerve atrophy (CSA of <= 4.4 mm2 after receiver operating
      characteristic curve analysis) had a lower 5-yr probability of maintaining pain
      relief after initial response than those without nerve atrophy (65% vs 86%, P =
      .04). CONCLUSION: Trigeminal nerve atrophy may predict pain recurrence in
      patients with initial post-GKS relief of CTN. Arterial and proximal NVC are not
      predictive of GKS outcomes. Future studies are required to determine optimal
      treatments for long-term pain relief in patients with CTN and trigeminal nerve
      atrophy.

PMID- 29660049
TI  - Ginsenoside Rg1 enhanced immune responses to infectious bursal disease vaccine in
      chickens with oxidative stress induced by cyclophosphamide.
AB  - This study was designed to evaluate the effect of oral administration of
      ginsenoside Rg1 on oxidative stress induced by cyclophosphamide in chickens.
      Ninety-six chickens were randomly divided into 4 groups, each consisting of 24
      birds. Groups 2 and 3 received intramuscular injection of cyclophosphamide at 100
      mg/kg body weight for 3 d to induce oxidative stress and immune suppression.
      Groups 1 and 4 were injected with saline in the same way as groups 2 and 3. Then
      chickens in group 3 were orally administrated Rg1 of 1 mg/kg body weight in
      drinking water for 7 d. After that, groups 1 to 3 were orally vaccinated with
      attenuated infectious bursal disease vaccine (Strain B87). Blood samples were
      collected for determination of infectious bursal disease virus-specific
      antibodies, cytokines, and oxidative parameters. Splenocytes were prepared for
      lymphocyte proliferation assay. The results showed that oral administration of
      ginsenoside Rg1 significantly enhanced specific antibody, IFN-gamma, and IL-6
      responses, and lymphocyte proliferation induced by concanavalin A and
      lipopolysaccharide in chickens injected with cyclophosphamide. Antioxidant
      activity of ginsenoside Rg1 was also observed in chickens by increased total
      antioxidant capacity, total superoxide dismutase, catalase, glutathione
      peroxidase, glutathione, ascorbic acid, and alpha-tocopherol, as well as
      decreased malondialdehyde and protein carbonyl. Therefore, oral administration of
      Rg1 was shown to improve the immune responses to infectious bursal disease
      vaccine in chickens suffering from oxidative stress.

PMID- 29660050
TI  - In Reply: Incidence and Predictive Factors of Sepsis Following Adult Spinal
      Deformity Surgery.

PMID- 29660051
TI  - Resection of Right Frontal Arteriovenous Malformation: 3-Dimensional Operative
      Video.
AB  - The video demonstrates resection of a Grade II Spetzler-Martin unruptured, medium
      sized arteriovenous malformation (AVM). A young woman presented with headaches
      and seizures. The right frontal lesion measured 4.5 cm in largest dimension and
      had superficial venous drainage. Partial Onyx embolization, primarily of the
      anterior cerebral feeding arteries, was performed. Bone removal for exposure
      allowed identification of indentation from the large superficial draining vein.
      The video demonstrates careful microsurgical dissection on the AVM/brain
      interface, with selective interruption of feeding arteries circumferentially. The
      lesion was removed after ligation of the large superficial draining vein.
      Postoperative day 1 and 1-yr angiography demonstrated complete resection. The
      patient's symptoms abated after resection. This case is presented with a waiver
      of informed consent as per the Institutional Review Board.

PMID- 29660052
TI  - Side-to-Side and End-to-Side Double Anastomosis Using the Parietal-Branch of the
      Superficial Temporal Artery-A Novel Technique for Extracranial to Intracranial
      Bypass Surgery: 3-Dimensional Operative Video.
AB  - In this 3-dimensional video, we perform a side-to-side and end-to-side double
      anastomosis using the parietal-branch of the superficial temporal artery (STA) to
      provide flow augmentation in a symptomatic 59-yr-old male with bilateral internal
      carotid artery occlusion at the origin, and left M1 segment occlusion. The
      patient suffered multiple left hemispheric strokes despite maximal medical
      therapy and was found to have poor hemodynamic reserve in the left hemisphere
      during evaluation with regional and global blood oxygenation level-dependent
      functional magnetic resonance imaging with CO2-challenge as well as quantitative
      magnetic resonance angiography and noninvasive optimal vessel analysis pre- and
      post-acetazolamide challenge. Postoperatively, the patient did very well and his
      hemodynamic studies improved significantly. The importance of this technique
      relies on the fact that we are using a single donor vessel to perform 2
      anastomoses, and carries the following advantages: (1) the frontal STA branch
      remains intact and therefore can still be used at a later time if further
      revascularization is needed; (2) wound complications related to devascularizing
      the scalp from harvesting both STA branches are reduced; (3) 2 vascular
      territories are augmented (frontal and temporal) while using a single donor; (4)
      we are maximizing donor potential and optimizing cut flow index (CFI; total
      bypass flow postanastomosis divided by bypass cut flow) by flow augmenting 2
      separate vascular beds therefore increasing demand. To explain that fourth point
      further: if the STA donor is able to carry a maximum 100 mL/min when cut, and
      after performing the first anastomosis bypass flow is only 37 mL/min, CFI will be
      37/100 = 0.37, reflecting low demand, a poor indicator of graft patency, as
      previously published.1,2 By adding a second anastomosis which demands an
      additional 60 mL/min from the same STA donor, CFI (60 + 37)/100 improves to 1.
      Institutional Review Board approval was obtained for the review of patient chart
      and video files. Informed consent was obtained directly from the patient via
      telephone regarding use of media for educational and publication purposes.

PMID- 29660053
TI  - Translational Science: Basic Science to Public Policy and Back Again.

PMID- 29660054
TI  - The Gateway Effect of e-cigarettes; Reflections on main Criticisms.

PMID- 29660055
TI  - Accuracy Assessment of Pedicle and Lateral Mass Screw Insertion Assisted by
      Customized 3D-Printed Drill Guides: A Human Cadaver Study.
AB  - BACKGROUND: Accurate cervical screw insertion is of paramount importance
      considering the risk of damage to adjacent vital structures. Recent research in 3
      dimensional (3D) technology describes the advantage of patient-specific drill
      guides for accurate screw positioning, but consensus about the optimal guide
      design and the accuracy is lacking. OBJECTIVE: To find the optimal design and to
      evaluate the accuracy of individualized 3D-printed drill guides for lateral mass
      and pedicle screw placement in the cervical and upper thoracic spine. METHODS:
      Five Thiel-embalmed human cadavers were used for individualized drill-guide
      planning of 86 screw trajectories in the cervical and upper thoracic spine. Using
      3D bone models reconstructed from acquired computed tomography scans, the drill
      guides were produced for both pedicle and lateral mass screw trajectories. During
      the study, the initial minimalistic design was refined, resulting in the advanced
      guide design. Screw trajectories were drilled and the realized trajectories were
      compared to the planned trajectories using 3D deviation analysis. RESULTS: The
      overall entry point and 3D angular accuracy were 0.76 +/- 0.52 mm and 3.22 +/-
      2.34 degrees , respectively. Average measurements for the minimalistic guides
      were 1.20 mm for entry points, 5.61 degrees  for the 3D angulation, 2.38 degrees 
      for the 2D axial angulation, and 4.80 degrees  for the 2D sagittal angulation.
      For the advanced guides, the respective measurements were 0.66 mm, 2.72 degrees ,
      1.26 degrees , and 2.12 degrees , respectively. CONCLUSION: The study ultimately
      resulted in an advanced guide design including caudally positioned hooks,
      crosslink support structure, and metal inlays. The novel advanced drill guide
      design yields excellent drilling accuracy.

PMID- 29660056
TI  - Pyomyositis: an unusual cause of hip pain in a patient on certolizumab pegol and
      leflunomide.

PMID- 29660057
TI  - Letter: Incidence and Predictive Factors of Sepsis Following Adult Spinal
      Deformity Surgery.

PMID- 29660058
TI  - Histological parameters to evaluate intestinal health on broilers challenged with
      Eimeria and Clostridium perfringens with or without enramycin as growth promoter.
AB  - The maintenance of integrity of the gastrointestinal tract is an important aspect
      for animal productivity, since it is able to absorb nutrients more efficiently
      and serves as a barrier against microorganisms. To control agents detrimental to
      intestinal integrity, growth-promoting antibiotics (AGP) are used, which reduce
      the number of toxin-producing microorganisms in the intestinal lumen, acting as
      anti-inflammatory agents. There is a demand for restriction of use of AGP in
      animal feed, but there are few studies showing what parameters we should observe
      to search for alternative additives. The aim of this study was to establish
      histological parameters that explain the effect of enramycin as growth promoter
      on intestinal health in broilers challenged with Eimeria and Clostridium
      perfringens. The zootechnical performance and the histology by I See Inside (ISI)
      methodology were evaluated on liver and ileum samples. Chickens challenged
      without AGP have the worst BWG, FCR, and histological ISI score (ISI score 9) in
      the ileum compared to non-challenged (ISI score 5). The use of enramycin on
      challenged group significantly minimized the ISI score in the ileum at 21 and 28
      d (ISI score 7.4 and 8.0, respectively) compared with the challenged group not
      fed with enramycin (ISI score 9.2 and 9.9, respectively), associated with reduced
      lamina propria thickness and inflammatory cell infiltration. We suggest these 2
      histological parameters as a standard to compare products for gut health.

PMID- 29660059
TI  - Menthol Cigarette use in Young Adult Smokers with Severe Mental Illnesses.
AB  - Introduction: Smokers with severe mental illness (SMI) are more likely to start
      smoking and less likely to quit. Menthol may facilitate smoking progression,
      dependence and maintenance by reducing harshness and irritation from smoking and
      providing a unique sensory experience during use. High rates of menthol use have
      been reported in smokers with SMI, but information on young adults with SMI has
      not been reported. Methods: This study provides a secondary analysis to assess
      the impact of menthol use in a pilot trial of brief tobacco interventions.
      Participants were assessed at baseline and again at a three-month follow-up with
      structured interviews and breath carbon monoxide to confirm self-reported 7-day
      abstinence at follow-up. Results: Participants included 81 young adult smokers
      with SMI, mean age of 24.2 years (SD=3.6; range 18-30). Overall, 58% of the group
      reported that they recently used a menthol-flavored product. Menthol use was
      correlated with race (African American [18/21, 85.7%] vs. White [24/53, 45.3%] or
      Other race [5/7, 71.4%]; X2=10.7, p=.005) and more lifetime psychiatric
      hospitalizations (t=2.39, p=.02), but not with cigarettes per day, nicotine
      dependence, quit attempts over the follow-up period, nor with achieving
      biologically confirmed abstinence at the follow-up assessment. Conclusions: The
      high prevalence of menthol flavored cigarette use in this study group is
      consistent with previous reports of high rates of menthol use among young adults,
      Blacks, and middle-aged SMI smokers. This study supports existing evidence that
      policies to restrict menthol flavoring in combustible tobacco products could
      reduce smoking in young adults with SMI. Implications: High rates of menthol use
      have been reported in middle-aged smokers with severe mental illness, but
      information on young adults with severe mental illness has not been reported. In
      this study, over half (58%) of 81 young adult smokers with severe mental illness
      used a menthol-flavored product. Menthol use was associated with race and with
      history of psychiatric hospitalizations. The research supports existing evidence
      that policies to restrict menthol flavoring in combustible tobacco products could
      reduce smoking in young adults with severe mental illness.

PMID- 29660060
TI  - Dietary effects of Bacillus subtilis fmbj on growth performance, small intestinal
      morphology, and its antioxidant capacity of broilers.
AB  - This paper aimed to study the dietary effects of Bacillus subtilis fmbj (BS fmbj)
      on growth performance, small intestinal histomorphology, and its antioxidant
      capacity of broilers at 21 d of raising. A total of 300 1-d old male Arbor Acres
      broilers were randomly assigned to 5 groups: broilers fed the basal diets with 0
      g/kg BS fmbj (CON), 0.2 g/kg BS fmbj (BS-1), 0.3 g/kg BS fmbj (BS-2), 0.4 g/kg BS
      fmbj (BS-3), and 0.5 g/kg BS fmbj (BS-4). The results showed that there were no
      differences in the growth performance among treatments during the trail. Dietary
      BS fmbj in broiler diets increased (P < 0.05) the serum immunoglobulin A (IgA)
      and immunoglobulin G (IgG) concentration, and enhanced the secretory
      immunoglobulin A (sIgA) level of small intestine (jejunum and ileum) compared
      with those in the CON group. The BS groups could improve (P < 0.05) the values of
      villus length, villus width, crypt depth, and villus area of small intestine
      compared with that in the CON group. Compared with the CON group, the BS group
      increased (P < 0.05) small intestinal antioxidant capacity and its mitochondrial
      antioxidant capacity, and also improved the antioxidant related-gene expression.
      The BS group exerted a lower (P < 0.05) level of oxidative damages in small
      intestine than that of the CON group. In conclusion, dietary BS fmbj in broiler
      diets was potential to improve the small intestinal histomorphology, small
      intestinal antioxidant capacity, and its mitochondrial antioxidant capacity. Thus
      this BS fmbj might be considered to be an important additive for the poultry
      industry.

PMID- 29660061
TI  - The change of volatile compounds of two kinds of vinasse-cured ducks during
      processing.
AB  - Vinasse-cured duck was processed by boiling, salting, and vinasse-dry-curing or
      vinasse-wet-curing. Volatile compounds, moisture contents, reducing sugars, and
      thiobarbituric acid reactive substances (TBARS) values during processing were
      determined. Reducing sugars decreased during boiling and increased after vinasse
      curing. TBARS values increased throughout the processing. The volatiles of ducks
      during processing and vinasse-curing agents (dry vinasse and vinasse sauce) were
      125 compounds. The first principal component (PC1) belonged to the flavor of
      cooked duck, whereas the second principal component (PC2) represented the flavor
      of yellow rice wine. The 66.49 and 29.61% of typical aroma of vinasse-dry-cured
      product were from dry vinasse and lipid oxidation, respectively, whereas the
      75.58 and 21.89% of aroma of vinasse-wet-cured product were from vinasse sauce
      and lipid oxidation, respectively. Lipid oxidation products increased after
      boiling, whereas salting promoted their release. Compared with vinasse-wet-cured
      duck, vinasse-dry-cured product presented richer aroma of lipid oxidation and
      weaker flavor of vinasse-curing agents. Besides, protein denaturation which was
      caused by ethanol could influence the retention and release of flavor. In
      conclusion, two kinds of vinasse-curing methods influenced the characteristic
      volatiles of products and their generation during processing.

PMID- 29660062
TI  - Minimally Invasive Exposure of the Maxillary Artery at the Anteromedial
      Infratemporal Fossa.
AB  - BACKGROUND: The maxillary artery (MA) has been described as a reliable donor for
      extracranial-intracranial high-flow bypass. Existing techniques to harvest MA
      require brain retraction and drilling of the middle fossa (with or without a
      zygomatic osteotomy), carrying the potential risks of venous bleeding, injury to
      the branches of the maxillary or mandibular nerves, muscular transection, or
      temporomandibular junction disorders. OBJECTIVE: To describe a novel technique to
      expose the MA without bony drilling and with minimal impact to surrounding
      structures. METHODS: A conventional curvilinear incision was performed in 10
      cadaveric specimens, prior to elevating the scalp to expose the zygomatic root
      and lateral orbital rim. The sphenozygomatic suture was followed to the
      anterolateral edge of the inferior orbital fissure (IOF) to locate and harvest
      the pterygoid segment of the MA. Topographic anatomy was assessed using
      surrounding landmarks and 3D Cartesian coordinates to define the surgical area.
      The number of visible MA branches and their lengths were recorded. RESULTS: The
      MA was successfully exposed in all specimens. This approach allowed 6 branches of
      MA to be exposed. The average length of exposure was 23.3 +/- 8.3 mm and the
      average surgical area was 2.8 +/- 0.9 cm2. The IOF was 11.5 +/- 4.2 mm from the
      MA. CONCLUSION: Our technique provides landmarks to identify the distal pterygoid
      segment of MA as a donor for extracranial-intracranial bypasses without the need
      for additional craniectomies. Clear anatomical landmarks, including the
      sphenozygomatic suture, anterolateral edge of IOF, infraorbital artery, and the
      pterygomaxillary fissure defined a trajectory to efficiently localize the MA with
      minimal risk to surrounding structures.

PMID- 29660063
TI  - Five successful pregnancies with antenatal anakinra exposure.
AB  - Objectives: Our aim is to add to the limited existing prospective data on IL-1
      inhibitor use in pregnancy. Methods: Data were obtained from the Organization of
      Teratology Information Specialists Autoimmune Disease in Pregnancy Project, a
      prospective cohort study of pregnancy outcomes in the USA and Canada. Eligible
      women were enrolled prior to 19 weeks' gestation between 2004 and 2017. Outcomes
      were obtained by maternal interview and medical record abstraction. Results: Five
      pregnancies with anakinra exposure were identified, all resulting in full-term
      singleton live births with no major or long-term complications. Three maternal
      subjects used anakinra for adult-onset Still's disease and two for systemic JIA.
      For all individuals who discontinued anakinra, some amount of steroid medication
      was necessary for treatment of disease flare. Two maternal subjects developed
      oligohydramnios, one also with pregnancy-induced hypertension. Two women had
      Caesarian sections, one medically indicated and one scheduled. One infant had low
      birth weight, but follow-up records indicated normal adjusted weight at 1 year.
      Three women successfully breastfed their infants, at least two of whom continued
      anakinra while breastfeeding. Conclusion: Anakinra was used successfully in five
      full-term pregnancies; however, two subjects developed oligohydramnios, a process
      that can be linked to fetal renal anomalies. Given previously reported cases of
      congenital renal anomalies associated with both antenatal anakinra use and
      maternal hyperthermia, the relationship between maternal IL-1 inhibitor use,
      uncontrolled maternal febrile disease and fetal outcomes should be further
      explored.

PMID- 29660065
TI  - In Reply: Angio-Architectural Features of High-Grade Intracranial Dural
      Arteriovenous Fistulas: Correlation With Aggressive Clinical Presentation and
      Hemorrhagic Risk.

PMID- 29660064
TI  - Health and Housework in Later Life: A Longitudinal Study of Retired Couples.
AB  - Objectives: To examine how changes in wives' and husbands' health influenced
      housework time and domestic outsourcing in retired couples. Method: We estimated
      fixed-effects models to test hypotheses about the gendered influence of health
      declines on absolute and relative measures of time spent on routine and
      nonroutine housework as well as the probability of outsourcing housework. The
      data were obtained from 23 waves of the German Socio-Economic Panel Study,
      comprising N = 25,119 annual observations of N = 3,889 retired couples aged 60-85
      years. Results: Wives' and husbands' housework time declined with health status,
      but these effects were large only for serious health problems. We found evidence
      for within-couple compensation of spouses' health declines, a mechanism that was
      limited to indispensable tasks of routine housework. The probability of getting
      paid help from outside the household increased with declining health, and this
      increase was more strongly tied to wives' health declines than to husbands'
      health declines. Discussion: The results demonstrate the relevance of health
      status for the performance of housework in retired couples. The evidence attests
      to the resilience of couples during later-life stages in which health issues may
      severely inhibit domestic productivity.

PMID- 29660066
TI  - Accidental Hypothermia Cardiac Arrest Treated Successfully with Invasive Body
      Cavity Lavage.

PMID- 29660067
TI  - Japanese spotted fever.

PMID- 29660069
TI  - Nocardia - A rare cause of brain Abscess.

PMID- 29660068
TI  - Re: Validation of the medical admission risk system (MARS): a combined
      physiological and laboratory risk prediction tool for 5- to 7-day in-hospital
      mortality. Ohman MC, et al. QJM. 2018. PMID: 29538743.

PMID- 29660070
TI  - Full-Length Transcriptome Sequencing and Modular Organization Analysis of the
      Naringin/Neoeriocitrin-Related Gene Expression Pattern in Drynaria roosii.
AB  - Drynaria roosii (Nakaike) is a traditional Chinese medicinal fern, known as
      'GuSuiBu'. The effective components, naringin and neoeriocitrin, share a highly
      similar chemical structure and medicinal function. Our HPLC-tandem mass
      spectrometry (MS/MS) results showed that the accumulation of
      naringin/neoeriocitrin depended on specific tissues or ages. However, little was
      known about the expression patterns of naringin/neoeriocitrin-related genes
      involved in their regulatory pathways. Due to a lack of basic genetic
      information, we applied a combination of single molecule real-time (SMRT)
      sequencing and second-generation sequencing (SGS) to generate the complete and
      full-length transcriptome of D. roosii. According to the SGS data, the
      differentially expressed gene (DEG)-based heat map analysis revealed that
      naringin/neoeriocitrin-related gene expression exhibited obvious tissue- and time
      specific transcriptomic differences. Using the systems biology method of modular
      organization analysis, we clustered 16,472 DEGs into 17 gene modules and studied
      the relationships between modules and tissue/time point samples, as well as
      modules and naringin/neoeriocitrin contents. We found that naringin/neoeriocitrin
      related DEGs distributed in nine distinct modules, and DEGs in these modules
      showed significantly different patterns of transcript abundance to be linked to
      specific tissues or ages. Moreover, weighted gene co-expression network analysis
      (WGCNA) results further identified that PAL, 4CL and C4H, and C3H and HCT acted
      as the major hub genes involved in naringin and neoeriocitrin synthesis,
      respectively, and exhibited high co-expression with MYB- and basic helix-leucine
      helix (bHLH)-regulated genes. In this work, modular organization and co
      expression networks elucidated the tissue and time specificity of the gene
      expression pattern, as well as hub genes associated with naringin/neoeriocitrin
      synthesis in D. roosii. Simultaneously, the comprehensive transcriptome data set
      provided important genetic information for further research on D. roosii.

PMID- 29660071
TI  - Assessing effects of yeast cell wall supplementation on threonine requirements in
      broilers as measured by performance and intestinal morphology.
AB  - The objective of this study was to evaluate whether or not the use of a prebiotic
      yeast cell wall (YCW) affects threonine requirements in starter broilers. Two
      hundred and forty 1-d-old Ross 308 broiler chickens were distributed among 2
      Petersime battery brooder units (48 pens; 5 birds per pen). Different threonine
      to lysine ratios (0.60, 0.65, and 0.70 to 1.0) with 1.22% available lysine with
      and without YCW at 250 ppm was fed to the chickens in order to evaluate
      performance and intestinal morphology over a 21-d trial. A basal diet with 22%
      protein and 2,980 kcal/kg ME was prepared to create the 6 dietary treatments. The
      calculated lysine concentration was 1.34%, whereas threonine was 0.81, 0.88, and
      0.94%, respectively. Pen weights and feed consumption were recorded at d 1, 7,
      14, and 21 of the experiment. Jejunal and ileal samples were collected on d 21
      for histology analysis to evaluate villi height (VH), crypt depth, villi width
      (VW), and muscularis thickness. A threonine to lysine ratio of 0.7:1.0 resulted
      in significant improvement of performance variables with increased jejunum VW and
      ileum VH compared with the other threonine to lysine ratios. Adding YCW to
      starter broiler did not affect the requirement for threonine.

PMID- 29660073
TI  - Creation of a formate: malate oxidoreductase by fusion of dehydrogenase enzymes
      with PEGylated cofactor swing arms.
AB  - Enzymatic biocatalysis can be limited by the necessity of soluble cofactors.
      Here, we introduced PEGylated nicotinamide adenine dinucleotide (NAD(H)) swing
      arms to two covalently fused dehydrogenase enzymes to eliminate their
      nicotinamide cofactor requirements. A formate dehydrogenase and cytosolic malate
      dehydrogenase were connected via SpyCatcher-SpyTag fusions. Bifunctionalized
      polyethylene glycol chains tethered NAD(H) to the fusion protein. This produced a
      formate:malate oxidoreductase that exhibited cofactor-independent ping-pong
      kinetics with predictable Michaelis constants. Kinetic modeling was used to
      explore the effective cofactor concentrations available for electron transfer in
      the complexes. This approach could be used to create additional cofactor
      independent transhydrogenase biocatalysts by swapping fused dehydrogenases.

PMID- 29660072
TI  - Bacterial communication between Lactobacillus spp. isolated from poultry in the
      inhibition of Salmonella Heidelberg-proof of concept.
AB  - Bacterial communication has become an increasingly studied topic aiming at the
      discovery of new products to aid the treatment of diseases for which conventional
      options do not work. The production of safe foods, free of pathogens, has been
      receiving increasing attention due to market demands for food products of high
      quality and free of residues. This study assessed the communication between
      Lactobacillus spp. during the in vitro inhibition of Salmonella Heidelberg (SH)
      and the impact an autoinducer produced by a strain of Lactobacillus plantarum has
      on communication in the normal microbiota and inhibiting SH in newborn chicks.
      For this purpose, the isolates of Lactobacillus spp. were isolated cloacal swabs
      of broilers and identified through biochemical and molecular assays and were
      obtained from broiler farms. They later had their inhibitory potential against SH
      stimulated after contact with the autoinducer. For assessing bacterial
      communication (quorum sensing) during the inhibition of SH by Lactobacillus spp.,
      a spot on the lawn assay was conducted. For the in vivo, 75 one-day-old chicks
      were divided in 5 experimental groups: control with no treatment; treatment with
      a Lactobacillus spp. pool on the first day; treatment with autoinducer on the
      second day; treatment with Lactobacillus spp. on the first day; and autoinducer
      on the second day and treatment without autoinducer. The autoinducer was assessed
      through an SH count in the ceca of the birds. The autoinducer produced by the
      strain of L. plantarum proved to be efficient for communicating with the other
      Lactobacillus spp. isolates as previous contact with SH induced the production of
      an autoinducer capable of increasing inhibition of SH both in vitro (in average
      132.73%) and in vivo, acting similarly to the Lactobacillus spp. pool (probiotic)
      by decreasing the SH count in the ceca (64%-24 h, 42%-96 h, and 46%-168 h).

PMID- 29660075
TI  - Acute medical risk scores: is MARS out of this world?

PMID- 29660076
TI  - Stereotype Threat Reduces the Positivity of Older Adults' Recall.
AB  - Objectives: As people get older, they show a relative preference to remember
      positive information over negative information. In two experiments, we tested
      whether the positivity of older adults' memory is affected by stereotype threat
      about age-related cognitive declines. We also tested whether highlighting a
      positive aging stereotype (older adults are wise) would inoculate older adults
      from stereotype threat's adverse effects. Method: In Experiments 1 and 2, we
      manipulated whether stereotypes about age-related cognitive decline were
      highlighted (stereotype threat) or mitigated (stereotype alleviation). In
      Experiment 2, we included a third condition (intervention + stereotype threat),
      which highlighted positive and negative aging stereotypes. Participants then saw
      emotionally evocative pictures and completed a memory test. Results: In both
      experiments, stereotype threat selectively reduced older adults' memory for
      positive pictures but did not affect their memory for negative pictures. This
      eliminated the positivity effect (i.e., the Age * Valence interaction; Experiment
      1). Our positive stereotype intervention did not reduce stereotype threat's
      adverse effect (Experiment 2). Discussion: Our findings show that the positivity
      effect is more robust when testing situations minimize stereotype threat. They
      also suggest that health interventions designed to capitalize on the positivity
      effect should ensure that ageist stereotypes are mitigated in the environment.

PMID- 29660074
TI  - The effect of triple therapy on the mortality of catastrophic anti-phospholipid
      syndrome patients.
AB  - Objectives: The objective of this study was to assess the effect that triple
      therapy (anticoagulation plus CS plus plasma exchange and/or IVIGs) has on the
      mortality risk of patients with catastrophic APS (CAPS) included in the CAPS
      Registry. Methods: Patients from the CAPS Registry were grouped based on their
      treatments: triple therapy; drugs included in the triple therapy but in different
      combinations; and none of the treatments included in the triple therapy. The
      primary endpoint was all-cause mortality. Multivariate logistic regression models
      were used to compare mortality risk between groups. Results: The CAPS Registry
      cohort included 525 episodes of CAPS accounting for 502 patients. After excluding
      54 episodes (10.3%), a total of 471 patients with CAPS were included [mean (s.d.)
      age 38.5 years (17); 68.2% female; primary APS patients 62%]. Overall, 174
      (36.9%) patients died. Triple therapy was prescribed in 189 episodes (40.1%),
      other combinations in 270 (57.3%) and none of those treatments in 12 episodes
      (2.5%); the mortality rate in the three groups was 28.6, 41.1 and 75%,
      respectively. Triple therapy was positively associated with a higher chance of
      survival when compared with non-treatment [adjusted odds ratio (OR) = 9.7, 95%
      CI: 2.3, 40.6] or treatment with other combinations of drugs included in the
      triple therapy (adjusted OR = 1.7, 95% CI: 1.2, 2.6). No statistical differences
      were found between patients that received triple therapy with plasma exchange or
      IVIGs (P = 0.92). Conclusion: Triple therapy is independently associated with a
      higher survival rate among patients with CAPS.

PMID- 29660077
TI  - Immediate Effects of a Single Session of Motor Skill Training on the Lumbar
      Movement Pattern During a Functional Activity in People With Low Back Pain: A
      Repeated-Measures Study.
AB  - Background: People with low back pain (LBP) may display an altered lumbar
      movement pattern of early lumbar motion compared to people with healthy backs.
      Modifying this movement pattern during a clinical test decreases pain. It is
      unknown whether similar effects would be seen during a functional activity.
      Objective: The objective of this study was to examine the lumbar movement
      patterns before and after motor skill training, effects on pain, and
      characteristics that influenced the ability to modify movement patterns. Design:
      The design consisted of a repeated-measures study examining early-phase lumbar
      excursion in people with LBP during a functional activity test. Methods: Twenty
      six people with chronic LBP received motor skill training, and 16 people with
      healthy backs were recruited as a reference standard. Twenty minutes of motor
      skill training to decrease early-phase lumbar excursion during the performance of
      a functional activity were used as a treatment intervention. Early-phase lumbar
      excursion was measured before and after training. Participants verbally reported
      increased pain, decreased pain, or no change in pain during performance of the
      functional activity test movement in relation to their baseline pain. The
      characteristics of people with LBP that influenced the ability to decrease early
      phase lumbar excursion were examined. Results: People with LBP displayed greater
      early-phase lumbar excursion before training than people with healthy backs (LBP:
      mean = 11.2 degrees , 95% CI = 9.3 degrees -13.1 degrees ; healthy backs: mean =
      7.1 degrees , 95% CI = 5.8 degrees -8.4 degrees ). Following training, the LBP
      group showed a decrease in the amount of early-phase lumbar excursion (mean
      change = 4.1 degrees , 95% CI = 2.4 degrees -5.8 degrees ); 91% of people with
      LBP reported that their pain decreased from baseline following training. The
      longer the duration of LBP (beta = - 0.22) and the more early-phase lumbar
      excursion before training (beta = - 0.82), the greater the change in early-phase
      lumbar excursion following training. Limitations: The long-term implications of
      modifying the movement pattern and whether the decrease in pain attained was
      clinically significant are unknown. Conclusions: People with LBP were able to
      modify their lumbar movement pattern and decrease their pain with the movement
      pattern within a single session of motor skill training.

PMID- 29660079
TI  - Completion task to uncover consumer's perception: a case study using distinct
      types of hen's eggs.
AB  - The choice and consumption of eggs are made considering a consumers'
      multidimensional perception, and their understanding becomes essential to the
      production targeting and the products' success in the market. In this context,
      this work aimed to verify the consumers' perception about the distinct types of
      hens' eggs, using a projective technique of completion task combined with
      presentation of images. A hundred consumers (n = 100) evaluated the main factors,
      both positive and negative, involved at the purchase time of eggs besides
      estimating their price. Between the positive factors that guide the eggs'
      consumption and purchase, the category with highest mention of terms was
      "Health," whereas negatively it was highlighted the category "Price." Concerning
      the perception of price, the results showed that the factory farm white eggs'
      value was the one that least differed from the average market price, possibly due
      to the nearness and familiarity with this variety. The methodology of completion
      task combined with presentation of images proved as being a practical and
      efficient tool to capture the consumers' perception of eggs, capable of providing
      valuable information to the ones involved in the production chain and
      commercialization of these products.

PMID- 29660078
TI  - Respirable Uranyl-Vanadate-Containing Particulate Matter Derived From a Legacy
      Uranium Mine Site Exhibits Potentiated Cardiopulmonary Toxicity.
AB  - Exposure to windblown particulate matter (PM) arising from legacy uranium (U)
      mine sites in the Navajo Nation may pose a human health hazard due to their
      potentially high metal content, including U and vanadium (V). To assess the toxic
      impact of PM derived from Claim 28 (a priority U mine) compared with background
      PM, and consider the putative role of metal species U and V. Two representative
      sediment samples from Navajo Nation sites (Background PM and Claim 28 PM) were
      obtained, characterized in terms of chemistry and morphology, and fractioned to
      the respirable (<= 10 MUm) fraction. Mice were dosed with either PM sample,
      uranyl acetate, or vanadyl sulfate via aspiration (100 ug), with assessments of
      pulmonary and vascular toxicity 24 h later. Particulate matter samples were also
      examined for in vitro effects on cytotoxicity, oxidative stress, phagocytosis,
      and inflammasome induction. Claim 28 PM10 was highly enriched with U and V and
      exhibited a unique nanoparticle ultrastructure compared with background PM10.
      Claim 28 PM10 exhibited enhanced pulmonary and vascular toxicity relative to
      background PM10. Both U and V exhibited complementary pulmonary inflammatory
      potential, with U driving a classical inflammatory cytokine profile (elevated
      interleukin [IL]-1beta, tumor necrosis factor-alpha, and keratinocyte
      chemoattractant/human growth-regulated oncogene) while V preferentially induced a
      different cytokine pattern (elevated IL-5, IL-6, and IL-10). Claim 28 PM10 was
      more potent than background PM10 in terms of in vitro cytotoxicity, impairment of
      phagocytosis, and oxidative stress responses. Resuspended PM10 derived from U
      mine waste exhibit greater cardiopulmonary toxicity than background dusts.
      Rigorous exposure assessment is needed to gauge the regional health risks
      imparted by these unremediated sites.

PMID- 29660080
TI  - Contributions of Ankle, Knee, Hip, and Trunk Muscle Function to Gait Performance
      in People With Multiple Sclerosis: A Cross-Sectional Analysis.
AB  - Background: The relative importance of lower extremity and trunk muscle function
      to gait in people with multiple sclerosis (MS) is unknown. Objective: This study
      aimed to investigate the association of lower extremity and trunk muscle function
      with gait performance in people who have MS and mild-to-moderate disability.
      Design: This was a cross-sectional, observational study. Methods: Participants
      were people who had an Expanded Disability Status Scale score of <= 5.5. Eleven
      lower extremity and trunk muscles were assessed using handheld dynamometry or
      endurance tests. Gait performance was assessed with the Timed 25-Foot (7.62 m)
      Walk (T25FW) and 6-Minute Walk Test (6MWT). Regression analysis was used to
      quantify the association between gait outcomes and muscle variables. Results:
      Seventy-two participants with MS and a mean Expanded Disability Status Scale
      score of 3.5 (SD = 1.14) were enrolled. Adjusted for age and sex, the
      multivariate model including hip abduction, ankle plantar flexion, trunk flexion,
      and knee flexion explained 57% of the adjusted variance in the T25FW; hip
      abduction, ankle plantar flexion, and trunk flexion explained 61% of the adjusted
      variance in the 6MWT. The strongest predictors were ankle plantar flexion
      endurance for the T25FW and hip abduction strength for the 6MWT: a 1-SD increase
      in ankle plantar flexion (15.2 heel-raise repetitions) was associated with a 0.33
      second reduction in the T25WT (95% CI = - 0.71 to - 0.14 seconds); a 1-SD
      increase in normalized hip abduction strength (0.14 kg/body mass index) was
      associated with a 54.4-m increase in the 6MWT (28.99 to 79.81 m). Limitations:
      Different measurement scales for independent variables were included because the
      muscle function assessment used either force or endurance. Conclusions: For the
      major muscles in the lower extremity and trunk, hip abduction, ankle plantar
      flexion, trunk flexion, and knee flexion were the strongest predictors of gait
      performance.

PMID- 29660081
TI  - Data-Driven Analysis of Functional Connectivity Reveals a Potential Auditory
      Verbal Hallucination Network.
AB  - Schizophrenia is a severe global health problem, with over half of such patients
      experiencing auditory verbal hallucinations (AVHs). A better understanding of the
      neural correlates differentiating patients experiencing AVHs from patients not
      experiencing AVHs and healthy controls may identify targets that lead to better
      treatment strategies for AVHs. Employing 2 data-driven, voxel-based measure of
      functional connectivity, we studied 46 patients with schizophrenia or
      schizoaffective disorder (28 experiencing AVHs and 18 not experiencing AVHs).
      Twenty healthy controls matched for age, gender, ethnicity, education level,
      handedness, and estimated verbal intelligence were included for comparison. The
      intrinsic connectivity distribution (ICD) was used to model each voxel's
      connectivity to the rest of the brain using a Weibull distribution. To
      investigate lateralization of connectivity, we used cross-hemisphere ICD, a
      method that separates the contribution of each hemisphere to interrogate
      connectivity laterality. Patients with AVHs compared with patients without AVHs
      exhibited significantly decreased whole-brain connectivity in the medial
      prefrontal cortex and posterior cingulate cortex, less lateralized connectivity
      in left putamen, and more lateralized connectivity in left interior frontal
      gyrus. Correlations with Auditory Hallucination Rating Scale (AHRS) and post hoc
      seed connectivity analyses revealed significantly altered network connectivity.
      Using the results from all analyses comparing the patient groups and correlations
      with AHRS, we identified a potential AVH network, consisting of 25 nodes, showing
      substantial overlap with the default mode network and language processing
      networks. This network as a whole, instead of individual nodes, may represent
      actionable targets for interventions.

PMID- 29660083
TI  - Limy bile syndrome.

PMID- 29660082
TI  - Molecular Components of Arabidopsis Intact Vacuoles Clarified with Metabolomic
      and Proteomic Analyses.
AB  - We analyzed the metabolites and proteins contained in pure intact vacuoles
      isolated from Arabidopsis suspension-cultured cells using capillary
      electrophoresis-mass spectrometry (CE-MS), Fourier transform-ion cyclotron
      resonance (FT-ICR)-MS and liquid chromatography (LC)-MS. We identified 21 amino
      acids and five organic acids as major primary metabolites in the vacuoles with CE
      MS. Further, we identified small amounts of 27 substances including well-known
      vacuolar molecules, but also some unexpected substances (e.g. organic phosphate
      compounds). Non-target analysis of the vacuolar sample with FT-ICR-MS suggested
      that there are 1,106 m/z peaks that could predict the 5,090 molecular formulae,
      and we have annotated 34 compounds in these peaks using the KNapSAck database. By
      conducting proteomic analysis of vacuolar sap, we found 186 proteins in the same
      vacuole samples. Since the vacuole is known as a major degradative compartment,
      many of these were hydrolases, but we also found various oxidoreductases and
      transferases. The relationships between the proteins and metabolites in the
      vacuole are discussed.

PMID- 29660084
TI  - Recent developments in biologic therapies for the treatment of patients with
      systemic lupus erythematosus.
AB  - SLE has a complex pathogenesis, and multiple therapeutic targets have been
      discovered in recent years. In spite of belimumab being approved by the US Food
      and Drug Administration and the widespread use of rituximab, there have been many
      failed attempts to treat SLE successfully using biologic agents. In this review,
      we consider newer biologic approaches that might offer the hope of improving the
      outcome of SLE patients. These include the fully humanized anti-CD20 mAbs,
      PEGylated anti-CD40L, IFNalpha inhibitors, rigerimod and immune complexes
      blockade.

PMID- 29660085
TI  - Pneumo-orbita causing optic nerve compression.

PMID- 29660086
TI  - How to improve success rates of endoscopic management for buried bumper syndrome.
AB  - Background: Buried bumper syndrome (BBS) is a rare complication of percutaneous
      endoscopic gastrostomy. Complete BBS without visible parts of the inner bumper is
      a challenge for endoscopic treatment. Methods and Aims: Data base analysis of all
      procedures performed at our tertiary university endoscopy center between 2000 and
      2015 was conducted. Our aim was to improve the success rates of endoscopic
      treatment using a standardized approach and a pull-modification of the
      papillotome-based extraction technique in a prospective cohort. Results:
      Retrospectively, 55 patients were identified (37 men; age 54 +/- 16 years). The
      prospective series comprised 11 patients (8 men; age 63 +/- 27 years). Patients
      with partial BBS were effectively treated by endoscopy in both cohorts (24/25 and
      4/4 patients, respectively). For complete BBS (Cyrany grade 3), success rates of
      endoscopic therapy differed significantly between the cohorts (P = 0.017). In the
      retrospective cohort, only 38% of patients (9/24 patients) were successfully
      treated. In the prospective cohort, all six patients (deep-type in five cases)
      were managed without complications. Patients with extra-gastric tubes underwent
      primary surgery in both cohorts (six and one patients, respectively). Conclusion:
      A structured approach improved success rates of endoscopic treatment. All
      patients with an internal bumper verified to lie within the gastric wall can be
      treated by an experienced investigator using a papillotome-based technique.

PMID- 29660087
TI  - Older Adults Pay an Additional Cost When Texting and Walking: Effects of Age,
      Environment, and Use of Mixed Reality on Dual-Task Performance.
AB  - Background: Texting while walking (TeWW) has become common among people of all
      ages, and mobile phone use during gait is increasingly associated with pedestrian
      injury. Although dual-task walking performance is known to decline with age, data
      regarding the effect of age on dual-task performance in ecological settings are
      limited. Objective: The objective of this study was to evaluate the effect of
      age, environment (indoors/outdoors), and mixed reality (merging of real and
      virtual environments) on TeWW performance. Design: A cross-sectional design was
      used. Methods: Young (n = 30; 27.8 +/- 4.4 years) and older (n = 20; 68.9 +/- 3.9
      years) adults performed single- and dual-task texting and walking indoors and
      outdoors, with and without a mixed reality display. Participants also completed
      evaluations of visual scanning and cognitive flexibility (Trail Making Test) and
      functional mobility (Timed "Up & Go" Test). Results: Indoors, similar
      interference to walking and texting occurred for both groups, but only older
      adults' gait variability increased under dual task conditions. Outdoors, TeWW was
      associated with larger age-related differences in gait variability, texting
      accuracy, and gait dual-task costs. Young adults with better visual scanning and
      cognitive flexibility performed TeWW with lower gait costs (r = 0.52-0.65). The
      mixed reality display was unhelpful and did not modify walking or texting.
      Limitations: Older adults tested in this study were relatively high functioning.
      Gaze of participants was not directly monitored. Conclusions: Although young and
      older adults possess the resources necessary for TeWW, older adults pay an
      additional "price" when dual-tasking, especially outdoors. TeWW may have
      potential as an ecologically valid assessment and/or an intervention paradigm for
      dual-task performance among older adults as well as for clinical populations.

PMID- 29660088
TI  - The MYB96 Transcription Factor Regulates Triacylglycerol Accumulation by
      Activating DGAT1 and PDAT1 Expression in Arabidopsis Seeds.
AB  - Maturing seeds stimulate fatty acid (FA) biosynthesis and triacylglycerol (TAG)
      accumulation to ensure carbon and energy reserves. Transcriptional reprogramming
      is a key regulatory scheme in seed oil accumulation. In particular, TAG assembly
      is mainly controlled by the transcriptional regulation of two key enzymes, acyl
      CoA:diacylglycerol acyltransferase 1 (DGAT1) and phospholipid:diacylglycerol
      acyltransferase 1 (PDAT1), in Arabidopsis seeds. However, the transcriptional
      regulators of these enzymes are as yet unknown. Here, we report that the R2R3
      type MYB96 transcription factor regulates seed oil accumulation by activating the
      genes encoding DGAT1 and PDAT1, the rate-limiting enzymes of the last step of TAG
      assembly. Total FA levels are significantly elevated in MYB96-overexpressing
      transgenic seeds, but reduced in MYB96-deficient mutant seeds. Notably, MYB96
      regulation of TAG accumulation is independent of WRINKLED 1 (WRI1)-mediated FA
      biosynthesis. Taken together, our findings indicate that FA biosynthesis and TAG
      accumulation are under independent transcriptional control, and MYB96 is mainly
      responsible for TAG assembly in seeds.

PMID- 29660089
TI  - A case of undetectable Glycated hemoglobin (HbA1C).

PMID- 29660091
TI  - Context before implementation: a qualitative study of decision makers' views of a
      peer-led healthy lifestyle intervention for people with serious mental illness in
      supportive housing.
AB  - People with serious mental illness die at an earlier age than people in the
      general population largely due to cardiovascular disease. Healthy lifestyle
      interventions can help reduce this health inequity. In this qualitative study, we
      examined the perceptions that decision makers in supportive housing agencies had
      toward a peer-led healthy lifestyle intervention and their views of contextual
      factors that could shape implementation at these agencies. A purposive sample of
      12 decision makers from three supportive housing agencies was recruited. We
      presented participants a vignette describing our peer-led intervention and used
      semistructured qualitative interviews to examine their views. Interviews were
      recorded, professionally transcribed, and analyzed using directed content
      analysis. Participants reported positive views toward the intervention with the
      most valued intervention attributes being relative advantage over existing
      services, compatibility to clients' needs, ability to pilot the intervention, and
      cost. A model emerged from our data depicting multilevel contextual factors
      believed to shape the implementation of our intervention at these agencies,
      including system- (funding, marketability, and external regulations),
      organization- (leadership support, fit with organization, staff buy-in and
      burden), and client-level (adaptability to clients' needs, and clients' buy-in)
      factors. Study findings illustrate the importance of understanding the context of
      practice before implementation. This examination can help identify critical views
      from decision makers that could undermine or advance the integration of peer-led
      interventions in supportive housing agencies and help identify structures,
      policies, and organizational practices that can inform the implementation
      process.

PMID- 29660090
TI  - Inhibition of left anterior intraparietal sulcus shows that mutual adjustment
      marks dyadic joint-actions in humans.
AB  - Creating real-life dynamic contexts to study interactive behaviors is a
      fundamental challenge for the social neuroscience of interpersonal relations.
      Real synchronic interpersonal motor interactions involve online, inter-individual
      mutual adaptation (the ability to adapt one's movements to those of another in
      order to achieve a shared goal). In order to study the contribution of the left
      anterior Intra Parietal Sulcus (aIPS) (i.e. a region supporting motor functions)
      to mutual adaptation, here, we combined a behavioral grasping task where pairs of
      participants synchronized their actions when performing mutually adaptive
      imitative and complementary movements, with the inhibition of activity of aIPS
      via non-invasive brain stimulation. This approach allowed us to investigate
      whether aIPS supports online complementary and imitative interactions. Behavioral
      results showed that inhibition of aIPS selectively impairs pair performance
      during complementary compared to imitative interactions. Notably, this effect
      depended on pairs' mutual adaptation skills and was higher for pairs composed of
      participants who were less capable of adapting to each other. Thus, we provide
      the first causative evidence for a role of the left aIPS in supporting mutually
      adaptive interactions and show that the inhibition of the neural resources of one
      individual of a pair is compensated at the dyadic level.

PMID- 29660092
TI  - Sandoz receives positive CHMP opinion for proposed biosimilar infliximab.

PMID- 29660093
TI  - Posts, pics, or polls? Which post type generates the greatest engagement in a
      Facebook physical activity intervention?
AB  - Social networking websites have attracted considerable attention as a delivery
      platform for physical activity interventions. Current evidence highlights a need
      to enhance user engagement with these interventions to actualize their potential.
      The purpose of this study was to determine which post type generates the most
      engagement from participants and whether engagement was related to change in
      physical activity in an intervention delivered via Facebook. Subgroup analysis of
      the intervention condition of a randomized controlled trial was conducted. The
      group moderator posted a new message to the private Facebook group each day of
      the program. The Facebook posts (n = 118) were categorized into the following
      types: moderator-initiated running program, multimedia, motivational, opinion
      polls, or discussion question and participant-initiated experience shares, or
      questions. Four metrics were used to measure volume of engagement with each post
      type, "likes," "comments," "poll votes," and "photo uploads." One-way ANOVA was
      used to determine whether engagement differed by post type and an independent
      samples t-test to determine differences in engagement between moderator and
      participant-initiated posts. Pearson correlation was used to examine associations
      between total engagement and change in physical activity. Engagement varied by
      post type. Polls elicited the greatest engagement (p <= .01). The most common
      form of engagement was "likes," and engagement was higher for moderator-initiated
      rather than participant-initiated posts (mean = 8.0 [SD 6.8] vs. 5.3 [SD 3.2]; p
      <= .01). Total engagement with the Facebook group was not directly associated
      with change in physical activity (r = -.13, p = .47). However, engagement was
      associated with compliance with the running program (r = .37, p = .04) and there
      was a nonsignificant positive association between compliance and change in
      physical activity (r = .32, p = .08). Posts requiring a simple response generated
      the most engagement. Intervention moderators should facilitate familiarity
      between participants at the intervention outset, to encourage engagement between
      participants. Engagement was related to change in physical activity, and these
      recommendations should be incorporated to enhance engagement and efficacy of
      interventions.

PMID- 29660094
TI  - Identifying which conduits are moving water in woody plants: a new HRCT-based
      method.
AB  - In vivo imaging methods are useful for examination of plant vascular tissues,
      particularly in the identification of fluid vs gas-filled conduits; however,
      these methods may not allow for the simple identification of conductive conduits.
      Our aim in the present study was to develop a method that would allow for the in
      vivo identification of conductive conduits. Intact plants and segments of
      grapevine (Vitis vinifera L.) and intact American chestnut (Castanea dentata
      (Marshall) Borkh.) saplings were examined. We found that iohexol, a water soluble
      iodine-rich molecule, was a useful contrast agent. We also stained the xylem of
      segments and gas- dried samples to compare between intact scans and excised
      segments. Iohexol could be readily fed through cut roots or stems into the
      transpiration stream, was successfully transported through the xylem and marked
      conductive vessels within high-resolution computed tomography (HRCT) scans.
      Iohexol results were comparable to those obtained by staining cut segments, with
      iohexol detecting greater numbers of smaller conduits in some samples. Samples
      contained gas-filled conduits, as well as both conductive (containing iohexol
      tracer) and non-conductive (no iohexol tracer) fluid-filled vessels. Fluid-filled
      non-conductive vessels were likely still developing or were not connected to the
      sap stream by a low resistance pathway. We found minimal differences between
      intact and excised segments other than excision-related dilution of iohexol. Both
      vessels and vasicentric tracheids were filled with iohexol in chestnut, providing
      a new tool to study the functions of these different cell types. The use of
      iohexol as a tracer to identify conductive vessels may greatly improve the
      utility of HRCT as a tool in the study of plant hydraulic function. Future
      studies using HRCT will likely need to incorporate conductive vessel markers or
      controls into experiments due to the presence of non-conductive fluid-filled
      vessels within the xylem.

PMID- 29660095
TI  - Effect of dietary Bacillus coagulans supplementation on growth performance and
      immune responses of broiler chickens challenged by Salmonella enteritidis.
AB  - This study was conducted to evaluate the protective efficacy of dietary Bacillus
      coagulans (B. coagulans) supplementation in birds receiving Salmonella
      enteritidis (SE). Two hundred and forty 1-day-old Cobb broilers were randomly
      assigned to 2 * 2 factorial arrangements of treatments with 2 levels of dietary
      B. coagulans (0 or 400 mg/kg) and 2 levels of SE challenge (0 or 1 * 109 SE
      between d 9 to 11). Results showed that SE infection did not affect growth
      performance, but caused intestinal inflammation and barrier function impairment
      by reducing intestinal goblet cells and beneficial bacteria numbers, increasing
      cecal Salmonella colonization and liver Salmonella invasion, downregulating
      jejunal mucin-2 (at 7 and 17 d post-infection, DPI), TLR2 (at 7 and 17 DPI), TLR4
      (at 17 DPI), TNFSF15 (at 7 and 17 DPI) gene mRNA levels, and upregulating jejunal
      IFN-gamma mRNA levels (at 17 DPI) compared to uninfected birds. Moreover, SE
      infection also elevated the concentration of jejunal anti-Salmonella IgA and sera
      anti-Salmonella IgG compared to uninfected birds. However, chickens received B.
      coagulans diets showed significant increase in body weight gain and weight gain
      to feed intake ratio from d 15 to 21, alkaline phosphatase activity (at 7 DPI),
      cecal Lactobacilli and Bifidobacterium numbers (at 7 DPI; at 17 DPI), villous
      height: crypt ratio (at 17 DPI), and goblet cell numbers (at 7 and 17 DPI),
      whereas exhibiting reduced jejunal crypt depth (at 17 DPI), cecal Escherichia
      coli (at 7, 17, and 31 DPI), and Salmonella (at 7 and 17 DPI) levels compared
      with the non-supplemented birds, regardless of SE infection. In addition, B.
      coagulans supplement upregulated lysozyme mRNA levels (at 17 DPI), downregulated
      IFN-gamma mRNA levels (at 7 and 17 DPI), showed an increased trend in Fowlicidin
      2 mRNA levels (at 7 DPI) and a reduced trend in liver Salmonella load compared to
      the non-supplemented control. These data indicated that B. coagulans has a
      protective effect in SE infected broilers.

PMID- 29660097
TI  - Personal Account: One Out of a Hundred.

PMID- 29660096
TI  - REFERENCE NEUTRON FIELDS IN CALIBRATION LABORATORY; SIMPLE DOSIMETRIC PARAMETERS
      AND THEIR CHANGES IN TIME.
AB  - The calibration laboratory revises periodically the dosimetric properties of its
      calibration fields. For reference neutron fields based on radionuclide sources,
      it is due to presence of isotopic impurities in the source ingredients.
      Consequently, in long term, the admixtures and their decay products become
      significant. Neglecting the impact of such effect leads to inconsistencies
      between the neutron emission rate observed during the measurements and the
      emission rate derived from the decay curve of the main isotope. In the Radiation
      Protection Measurements Laboratory at the National Centre for Nuclear Research
      the neutron fields of the bare sources of 252Cf, 241AmBe and 239PuBe have been
      examined for nearly 30 years, regularly, in fixed geometry. Additionally, at the
      particular point of a calibration bench, determination of neutron fluence rate,
      ambient dose equivalent rate and its scattered component, total neutron and gamma
      dose rate, gamma to total dose ratio, radiation quality factor and total tissue
      kerma are occasionally determined. In this article, we would like to present
      recently achieved results and their comparison with the measurement data formerly
      presented. The growth of the neutron emission of 239PuBe source, as well as
      discrepancies between the decay curves of relevant isotopes and the emission rate
      of 252Cf and 241AmBe will be presented.

PMID- 29660098
TI  - ESTIMATION OF RADIATION DOSES FROM ABDOMINAL COMPUTED TOMOGRAPHY SCANS.
AB  - A total of 120 adult female and male patients randomly selected from 10 hospitals
      in the West Bank and Gaza Strip were investigated for organ and effective doses
      from abdominal computed tomography scan. The organs considered in this study are
      liver, stomach and colon. Assessment of radiation doses was performed by using a
      commercially available Monte Carlo based software VirtualDoseTM CT, a product of
      Virtual Phantoms, Inc. The software utilizes male and female tissue equivalent
      mathematical phantoms of all ages and sizes from new born up to morbidly obese
      patients. The corresponding phantom was selected for every patient according to
      patient's demographic parameters. Patient demographic data, scanning parameters
      and dose indicators (including patient body mass index (BMI), milliampere-second
      (mAs), X-ray tube kilovoltage (kVp), computed tomography dose index (CTDIvol),
      dose length product (DLP), manufacturer, name and type of operated CT scanner)
      were recorded for every examination. The collected parameters were used to
      calculate the organ and effective doses for every patient. The highest estimated
      patient organ doses were 25 mGy for liver, 20 mGy for stomach and 30 mGy for
      colon for a male patient with BMI of 30 kg/m2 and 90 kg of weight. This patient
      correspondent effective dose was 9 mSv. The average effective dose for the entire
      patient population was 5.5 mSv with a range between 2 and 10 mSv. The highest
      effective dose was found for a female patient with a BMI of 26.6 kg/m2, and 77 kg
      of weight. This patient correspondent organ doses were 14, 9 and 14 mGy for the
      liver, stomach and colon, respectively. The average organs doses per patient
      estimated for patients from all investigated hospitals were 13.1, 7.6 and 13.2
      mGy for liver, stomach and colon, respectively. Both effective dose and organ
      doses increase with BMI and body weight. In general, the estimated radiation
      doses from abdominal CT examinations in this study are low and comparable with
      those published in the literature.

PMID- 29660099
TI  - Age alters uptake pattern of organic and inorganic nitrogen by rubber trees.
AB  - Several studies have explored plant nutrient acquisition during ecosystem
      succession, but it remains unclear how age affects nitrogen (N) acquisition by
      the same tree species. Clarifying the age effect will be beneficial to
      fertilization management through improving N-use efficiency and reducing the risk
      of environmental pollution due to NO3- leaching. To clarify the effect of age on
      N uptake, rubber (Hevea brasiliensis (Willd. ex A. Juss.) Muell. Arg.)
      plantations of five ages (7, 16, 24, 32 and 49 years) were selected in
      Xishuangbanna of southern China for brief 15N exposures of intact roots using
      field hydroponic experiments. 15N-labeled NH4+, NO3- or glycine were applied in
      this study. All targeted rubber trees uptake rates followed an order of NH4+ >
      glycine > NO3-. As age increased, NH4+ uptake increased first and then decreased
      sharply, partly consistent with the pattern of soil NH4+ concentrations. Uptake
      of glycine decreased first and then increased gradually, while no significant
      change of NO3- uptake rates existed with increasing age. Overall, rubber trees
      with ages from 7 to 49 years all showed a preference for NH4+ uptake. Young
      rubber trees (7 and 16 years) had higher NH4+ and lower glycine preferences than
      older trees (24, 32 and 49 years). Mycorrhizal colonization rates of rubber trees
      were higher in intermediately aged plantations (16, 24 and 32 years) than in
      plantations aged 7 and 49 years. A positive relationship was observed between
      arbuscular mycorrhizal colonization rates and NO3- preference. The results from
      this study demonstrate that rubber trees do not change their preference for NH4+
      but strongly decreased their reliance on it with age. These findings indicate
      that the shift of N uptake patterns with age should be taken into account for
      rubber fertilization management to improve N-use efficiency and reduce the risk
      of environmental pollution during rubber production.

PMID- 29660100
TI  - Assessment of Iodine Nutritional Status of School-Age Children in Kolkata
      District of West Bengal State in Post-Iodation Scenario.
AB  - To evaluate the state of iodine nutrition in post-iodation scenario, 3500
      children were examined clinically for endemic goitre. Iodine and thiocyanate were
      measured in 240 urine samples; iodine content in 210 salt samples was measured.
      Total goitre prevalence was 6.1%. Median urinary iodine level was 21.80 ug/dl,
      and mean (+/-SD) urinary thiocyanate was 0.89 +/- 0.49 mg/dl. Iodine content of
      only 11.9% salt samples was below recommended level of 15 ppm, 25.2% was between
      15 and 30 ppm and 62.9% was >30 ppm. Iodine deficiency disorders are thus
      clinically mild public health problem of the studied population; however, they
      have no biochemical iodine deficiency. Studied population found exposed to
      thiocyanate load that might be the possible cause for persistence of endemic
      goitre. People of Kolkata should be advised to eat commonly consumed goitrogenic
      foods after boiling and decanting the water. Periodical monitoring and evaluation
      of iodine status should be mandatory.

PMID- 29660101
TI  - Stand development and other intrinsic factors largely control fine-root dynamics
      with only subtle modifications from resource availability.
AB  - Forest productivity depends on resource acquisition by ephemeral roots and
      leaves. A combination of intrinsic and environmental factors influences ephemeral
      organs; however, difficulties in studying belowground organs impede mechanistic
      understanding of fine-root production and turnover. To quantify factors
      controlling fine-root dynamics, we grew a deciduous hardwood (Populus deltoides
      Bartr.) and an evergreen conifer (Pinus taeda L.) with distinct soil moisture and
      nutrient availability treatments. We monitored fine-root dynamics with
      minirhizotrons for 6 years during early stand development and expressed results
      on a root length, biomass and mortality-risk basis. Stand development and other
      intrinsic factors consistently influenced both species in the same direction and
      by similar magnitude. Live-root length increased to a peak during establishment
      and slowly declined after roots of neighboring trees overlapped. Root longevity
      was highest during establishment and decreased thereafter. Root longevity
      consistently increased with depth of appearance and initial root diameter. Season
      of appearance affected root longevity in the following order: spring > summer >
      fall > winter. The influence of soil resource availability on fine-root dynamics
      was inconsistent between species, and ranked below that of rooting depth, initial
      diameter, stand development and phenology. Fine-root biomass either increased or
      was unaffected by greater resource availability. Fine-root production and live
      root length decreased with irrigation for both species, and increased with
      fertilization only for poplar. Fine-root mortality risk both increased and
      decreased depending on species and amendment treatment. Differing responses to
      soil moisture and nutrient availability between species suggests we should
      carefully evaluate generalizations about the response of fine-root dynamics to
      resource availability. While attempting to describe and explain carbon allocation
      to fine-root production and turnover, modelers and physiologists should first
      consider consistent patterns of allocation caused by different depth, diameter,
      stand development, phenology and species before considering allocation due to
      soil resource availability.

PMID- 29660102
TI  - Psychopathic traits influence amygdala-anterior cingulate cortex connectivity
      during facial emotion processing.
AB  - There is accumulating evidence that youths with antisocial behavior or
      psychopathic traits show deficits in facial emotion recognition, but little is
      known about the neural mechanisms underlying these impairments. A number of
      neuroimaging studies have investigated brain activity during facial emotion
      processing in youths with Conduct Disorder (CD) and adults with psychopathy, but
      few of these studies tested for group differences in effective connectivity-i.e.
      changes in connectivity during emotion processing. Using functional magnetic
      resonance imaging and psycho-physiological interaction methods, we investigated
      the impact of CD and psychopathic traits on amygdala activity and effective
      connectivity in 46 male youths with CD and 25 typically-developing controls when
      processing emotional faces. All participants were aged 16-21 years. Relative to
      controls, youths with CD showed reduced amygdala activity when processing angry
      or sad faces relative to neutral faces, but the groups did not significantly
      differ in amygdala-related effective connectivity. In contrast, psychopathic
      traits were negatively correlated with amygdala-ventral anterior cingulate cortex
      connectivity for angry vs neutral faces, but were unrelated to amygdala responses
      to angry or sad faces. These findings suggest that CD and psychopathic traits
      have differential effects on amygdala activation and functional interactions
      between limbic regions during facial emotion processing.

PMID- 29660103
TI  - Submicroscopic Plasmodium falciparum parasitaemia in human immunodeficiency virus
      infected adults living in Gabon (Central Africa)-a pilot study.
AB  - Background: Submicroscopic malaria infections contribute to malaria transmission.
      Describing the extent of the parasite reservoir is of importance. In people
      living with human immunodeficiency virus (HIV), the frequency of subpatent
      malaria infections is rarely reported. The aim of the present study was to
      determine the frequency of submicroscopic infections in people living with HIV in
      Gabon and its relationship with cotrimoxazole (CTX) use. Methods: A survey was
      conducted in two health care centres in rural areas (Koulamoutou and Oyem) and
      three in urban areas (Libreville) of Gabon from March 2015 to June 2016. Blood
      samples were collected from consenting people living with HIV with a negative
      blood smear. Information on CTX and antiretroviral therapy intake was recorded
      from the medical file of the patient and through an interview. For molecular
      analysis, the Plasmodium small subunit ribosomal RNA gene was amplified by nested
      polymerase chain reaction. Results: Submicroscopic infections were detected in
      10.1% (n=12/119) of the people living with HIV, more frequently in those residing
      in rural areas (15.1%) compared with urban areas (2.1%) (p<0.01). The proportion
      of anaemic patients was 1.74-fold more frequent in malaria-infected patients,
      although not statistically significant. Submicroscopic infections frequency did
      not vary according to CTX intake (p=0.6). Conclusions: The present pilot study
      highlights a non-negligible frequency of submicroscopic malaria infections in
      people living with HIV from rural areas, but no relationship with CTX intake was
      found.

PMID- 29660104
TI  - DEVELOPMENT OF AN IONIZATION CHAMBER FOR LOW AND MEDIUM ENERGY PHOTON DOSIMETRY.
AB  - Measurement of dose due to low and medium energy X-ray using an ionization
      chamber needs special considerations as the wall thickness of the detector plays
      an important role in signal generation. A thin and plane wall ionization chamber
      having 900 cc volume was developed to study its calibration coefficient with air
      kerma (Kair) rate and ambient dose equivalent (H*(10)) rate at various X-ray beam
      qualities generated from a dosimetry grade X-ray machine. Optimized ionization
      chamber wall thickness was determined through measurements where a flat energy
      response of the ionization chamber could be established. The measurement shows
      that the air kerma rate based calibration coefficient for ionization chamber
      varies up to 45% and ambient dose equivalent rate based calibration coefficient
      varies up to 20% for wall thickness 1.2-1200 mg/cm2 in the energy range 17.6-213
      keV.

PMID- 29660105
TI  - The impact of non-persistence on the direct and indirect costs in patients
      treated with subcutaneous tumour necrosis factor-alpha inhibitors in Germany.
AB  - Objective: The goal of the present study was to estimate the treatment costs in
      immune-mediated rheumatic disease patients initiating treatment with an s.c.
      biologic agent based on treatment persistence. Methods: This is a retrospective
      cohort study based on the German statutory health insurance funds database.
      Patients ?18 years of age with a diagnosis of AS, PsA or RA treated with s.c. TNF
      alpha inhibitors (TNFis) were included. Persistence was estimated as the duration
      of time from s.c. TNFi therapy initiation to discontinuation, which was defined
      as at least 60 days without therapy. We performed 1:1 matching based on a
      propensity score that was constructed as the conditional probability of being
      persistent as a function of age, gender, index year, physician specialty and
      Charlson comorbidity index. Finally, the cost differences between the matched
      pairs were estimated using the Wilcoxon test. Results: After 1:1 matching, 678
      persistent and 678 non-persistent patients were available for cost analyses.
      Using a 2-year time period, the costs for office-based visits per patient were
      ?2319 in the persistent cohort compared with ?3094 in the non-persistent cohort
      (P < 0.001). Co-medication costs were ?2828 in the persistent cohort compared
      with ?5498 in the non-persistent cohort, hospitalization costs were ?3551 in the
      persistent cohort compared with ?5890 in the non-persistent cohort and sick leave
      costs were ?717 in the persistent cohort compared with ?1241 in the non
      persistent cohort (all P < 0.001). Conclusion: The results of this study indicate
      that persistence with s.c. TNFi treatment can be associated with several cost
      offsets for immune-mediated rheumatic disease patients.

PMID- 29660106
TI  - Safety, effectiveness and feasibility of outpatient management of children with
      pneumonia with chest indrawing at Port Moresby General Hospital, Papua New
      Guinea.
AB  - Implementing the World Health Organization (WHO) recommendations on home-based
      management of pneumonia with chest indrawing is challenging in many settings. In
      Papua New Guinea, 120 children presenting with the WHO definition of pneumonia
      were screened for danger signs, comorbidities and hypoxaemia using pulse
      oximetry; 117 were appropriate for home care. We taught mothers about danger
      signs and when to return, using structured teaching materials and a video. The
      children were given a single dose of intramuscular benzylpenicillin, then sent
      home on oral amoxicillin for 5 days, with follow-up at Days 2 and 6. During the
      course of treatment, five (4%) of the 117 children were admitted and 15 (13%)
      were lost to follow-up. There were no deaths. Treating children with pneumonia
      with chest indrawing but no danger signs is feasible as long as safeguards are in
      place-excluding high-risk patients, checking for danger signs and hypoxemia and
      providing education for mothers and follow-up.

PMID- 29660107
TI  - Recess environment and curriculum intervention on children's physical activity:
      IPLAY.
AB  - Understanding the impacts of the built environment on physical activity (PA) is
      essential to promoting children's PA. The purpose of this study was to
      investigate the effects of schoolyard renovations and a PA recess curriculum
      alone and in combination on children's PA. This was a 2 (learning landscape [LL]
      vs. non-LL) * 2 (curriculum intervention vs. no curriculum intervention)
      factorial design with random assignment to the curriculum intervention, and six
      elementary schools per condition. PA outcomes were assessed preprogram, mid
      program, immediate postprogram, and one year postprogram. No meaningful
      intervention effects were found. Lack of an effect may be due to the brief dose
      of recess, the curriculum not being integrated within the schoolyard, the LL
      implementation occurring prior to the study, or the already high levels of PA.
      Potential avenues to promote PA include making recess longer, integrating recess
      into the school curricula, and developing recess PA curricula integrating
      schoolyards.

PMID- 29660108
TI  - Early development of the longsnout seahorse Hippocampus reidi (Syngnathidae)
      within the male brood pouch.
AB  - Fertilized and unfertilized eggs and embryos of the longsnout seahorse
      Hippocampus reidi were collected at different stages of development and provided
      the basis for a description of morphological development from fertilization until
      release from the paternal pouch. Images of fertilized eggs, as well as their
      rupture after a few minutes in seawater are reported for the first time. The yolk
      sac transitioned from ovoid to spherical shape and was reabsorbed progressively
      until release. The tail began rising from the surface of the deuteroplasm while
      embryos were in the egg envelope. Embryos lacked a primordial fin fold and
      developed some species characteristics, such as rays in the dorsal fin, before
      resorption of the yolk sac. At release, juvenile seahorses were in an advanced
      stage of development even if they lacked important adult characteristics, such as
      ring plates and coronet. The tail was not prehensile in juveniles at release; a
      small caudal fin was present, although this fin is lost in adults.

PMID- 29660109
TI  - Screening for emotional disorders in patients with cancer using the Brief Symptom
      Inventory (BSI) and the BSI-18 versus a standardized psychiatric interview (the
      World Health Organization Composite International Diagnostic Interview).
AB  - BACKGROUND: Given the adverse consequences of psychiatric and psychosocial
      morbidity on the quality of life for patients with cancer, prompt detection of
      psychological symptoms is mandatory. The authors examined the properties and
      accuracy of the Brief Symptom Inventory (the 53-item version [BSI] and the 18
      item version [BSI-18]) for the detection of psychiatric morbidity compared with
      the World Health Organization Composite International Diagnostic Interview (CIDI)
      for International Classification of Diseases-10th Revision psychiatric diagnoses.
      METHODS: A convenience sample of 498 patients with newly diagnosed cancer who
      were recruited in cancer outpatient services participated in the CIDI interview
      and in BSI and BSI-18 assessments. RESULTS: The prevalence of psychiatric
      morbidity was 39.75%. When participants were classified as cases using the BSI
      standard case rule, agreement with the CIDI was potentially acceptable
      (sensitivity, 72.7%; specificity, 88.7%). In contrast, the accuracy of the BSI-18
      in identifying cases was poor according to the standard case rule, with very low
      sensitivity (29.3%) (misclassification rate, 28.7%). By using a first alternative
      case-rule system (a BSI-18 global severity index [GSI] T-score >=57), sensitivity
      marginally improved (45%), whereas a second alternative case-rule system (a GSI T
      score >=50) significantly increased sensitivity (77.3%). In receiver operating
      characteristic curve analysis, a further cutoff GSI T-score >=48 exhibited good
      discrimination levels (sensitivity, 82.3%; specificity, 72.4%). There were some
      differences in GSI cutoff T-scores according to the International Classification
      of Diseases-10th Revision diagnosis and sex. CONCLUSIONS: The BSI appeared to
      have acceptable diagnostic accuracy compared with a standardized psychiatric
      interview. For the BSI-18, it is mandatory to use alternative case-rule systems,
      to identify patients with psychiatric morbidity. Cancer 2018;124:2415-26. (c)
      2018 American Cancer Society.

PMID- 29660110
TI  - Preparation of high-purity lactulose through efficient recycling of catalyst
      sodium aluminate and nanofiltration: a pilot-scale purification.
AB  - BACKGROUND: Lactulose, a valuable lactose-originated 'bifidus factor' product, is
      exclusively produced by chemical-based isomerization commercially. A complexing
      agent of sodium aluminate exhibiting high conversion efficiency and strong
      recyclable stability is more practical for industrial applications. In this
      study, efficient purification of high-purity lactulose through recycling of
      sodium aluminate and further desalination by nanofiltration (NF) was implemented
      on a pilot scale. RESULTS: Over 99.5% of the catalyst was prior recycled in the
      form of Al(OH)3 precipitate by pH-induced precipitation and centrifugation;
      residual aluminum was further absorbed by ion exchange resin to an acceptable
      level (<=10 mg kg-1 ). Subsequently, impurities (monosaccharides and NaCl) were
      ideally separated from lactulose syrup by NF based on their significant retention
      differences (lactulose 94.8-97.2% > lactose 86.2-93.5% > monosaccharides 36.3
      48.7% > NaCl 9.5-31.1%). High-purity (>95%) lactulose was obtained with >90%
      yield in both constant and variable volume diafiltration (CVD and VVD) modes when
      the volume dilution ratio (Vc /Vf ) was 4.0 and 2.5 respectively. Both
      experimental and predicted results showed that the VVD mode was more water-saving
      in practice. CONCLUSION: This is the first trial purification of lactulose syrup
      from chemical isomerization of lactose catalyzed by sodium aluminate, and the
      applied methodology is a promising industrial-scale purification strategy. (c)
      2018 Society of Chemical Industry.

PMID- 29660111
TI  - Confidence in Attachment Relationships and Marital Status as Protective Factors
      for Self-Perceived Parental Role and In-Person Visitation with Children Among
      Incarcerated Fathers.
AB  - The study aimed at investigating the role of confidence in attachment
      relationships and marital status as protective factors for incarcerated fathers'
      self-perceived parental role and in-person contacts with their children.
      Participants included 150 inmate fathers and 145 nonincarcerated control fathers
      who provided background sociodemographic information and completed two self
      reports, the Attachment Style Questionnaire and the Self-Perception of Parental
      Role. A two-phased cluster analytic plan allowed us to highlight two profiles of
      self-perceived parental roles, with incarceration and low confidence in
      attachment relationships increasing the risk of the less optimal of the two
      profiles. Higher confidence in attachment relationships and having a stable
      romantic relationship increased the likelihood of incarcerated fathers engaging
      in frequent contacts with their children, while the profile of self-perceived
      parental role had no effect. Implications for practice are discussed, and
      suggestions for further research are provided.

PMID- 29660113
TI  - Systematic review of the influence of socioeconomic deprivation on mortality
      after colorectal surgery.
AB  - BACKGROUND: Socioeconomic deprivation is a potentially important factor
      influencing surgical outcomes. This systematic review aimed to summarize the
      evidence for any association between socioeconomic group and mortality after
      colorectal surgery, and to report the definitions of deprivation used and the
      approaches taken to adjust for co-morbidity in this patient population. METHODS:
      MEDLINE, Embase, the Cochrane Library and Web of Science were searched for
      studies up to November 2016 on adult patients undergoing major colorectal
      surgery, which reported on mortality according to socioeconomic group. Risk of
      bias and study quality were assessed by extracting data relating to study size,
      and variations in inclusion and exclusion criteria. Quality was assessed using a
      modification of a previously described assessment tool. RESULTS: The literature
      search identified 59 studies published between 1993 and 2016, reporting on 2 698
      403 patients from eight countries. Overall findings showed evidence for higher
      mortality in more deprived socioeconomic groups, both in the perioperative period
      and in the longer term. Studies differed in how they defined socioeconomic
      groups, but the most common approach was to use one of a selection of
      multifactorial indices based on small geographical areas. There was no consistent
      approach to adjusting for co-morbidity but, where this was considered, the
      Charlson Co-morbidity Index was most frequently used. CONCLUSION: This systematic
      review suggests that socioeconomic deprivation influences mortality after
      colorectal surgery.

PMID- 29660112
TI  - Evaluation of membrane-bound and soluble forms of human leucocyte antigen-G in
      systemic sclerosis.
AB  - Systemic sclerosis (SSc) is a complex disease characterized by immune
      dysregulation, extensive vascular damage and widespread fibrosis. Human leucocyte
      antigen-G (HLA-G) is a non-classic class I major histocompatibility complex (MHC)
      molecule characterized by complex immunomodulating properties. HLA-G is expressed
      on the membrane of different cell lineages in both physiological and pathological
      conditions. HLA-G is also detectable in soluble form (sHLA-G) deriving from the
      shedding of surface isoforms (sHLA-G1) or the secretion of soluble isoforms (HLA
      G5). Several immunosuppressive functions have been attributed to both membrane
      bound and soluble HLA-G molecules. The plasma levels of sHLA-G were higher in SSc
      patients (444.27 +/- 304.84 U/ml) compared to controls (16.74 +/- 20.58 U/ml) (P
      < 0.0001). The plasma levels of transforming growth factor (TGF)-beta were higher
      in SSc patients (18 937 +/- 15 217 pg/ml) compared to controls (11 099 +/- 6081
      pg/ml; P = 0.003), and a significant correlation was found between TGF-beta and
      the plasma levels of total sHLA-G (r = 0.65; P < 0.01), sHLA-G1 (r = 0.60; P =
      0.003) and HLA-G5 (r = 0.47; P = 0.02). The percentage of HLA-G-positive
      monocytes (0.98 +/- 1.72), CD4+ (0.37 +/- 0.68), CD8+ (2.05 +/- 3.74) and CD4+
      CD8+ double-positive cells (14.53 +/- 16.88) was higher in SSc patients than in
      controls (0.11 +/- 0.08, 0.01 +/- 0.01, 0.01 +/- 0.01 and 0.39 +/- 0.40,
      respectively) (P < 0.0001). These data indicate that in SSc the secretion and/or
      shedding of soluble HLA-G molecules and the membrane expression of HLA-G by
      peripheral blood mononuclear cells (PBMC) is clearly elevated, suggesting an
      involvement of HLA-G molecules in the immune dysregulation of SSc.

PMID- 29660114
TI  - Molecular evolution of key metabolic genes during transitions to C4 and CAM
      photosynthesis.
AB  - PREMISE OF THE STUDY: Next-generation sequencing facilitates rapid production of
      well-sampled phylogenies built from very large genetic data sets, which can then
      be subsequently exploited to examine the molecular evolution of the genes
      themselves. We present an evolutionary analysis of 83 gene families (19
      containing carbon-concentrating mechanism (CCM) genes, 64 containing non-CCM
      genes) in the portullugo clade (Caryophyllales), a diverse lineage of mostly arid
      adapted plants that contains multiple evolutionary origins of all known
      photosynthesis types in land plants (C3 , C4 , CAM, C4 -CAM, and various
      intermediates). METHODS: We inferred a phylogeny of 197 individuals from 167 taxa
      using coalescent-based approaches and individual gene family trees using maximum
      likelihood. Positive selection analyses were conducted on individual gene family
      trees with a mixed effects model of evolution (MEME). We devised new indices to
      compare levels of convergence and prevalence of particular residues between CCM
      and non-CCM genes and between species with different photosynthetic pathways. KEY
      RESULTS: Contrary to expectations, there were no significant differences in the
      levels of positive selection detected in CCM versus non-CCM genes. However, we
      documented a significantly higher level of convergent amino acid substitutions in
      CCM genes, especially in C4 taxa. CONCLUSIONS: Our analyses reveal a new suite of
      amino acid residues putatively important for C4 and CAM function. We discuss both
      the advantages and challenges of using targeted enrichment sequence data for
      exploratory studies of molecular evolution.

PMID- 29660115
TI  - A working model for hypothermic neuroprotection.
AB  - Therapeutic hypothermia significantly improves survival without disability in
      near-term and full-term newborns with moderate to severe hypoxic-ischaemic
      encephalopathy. However, hypothermic neuroprotection is incomplete. The challenge
      now is to find ways to further improve outcomes. One major limitation to progress
      is that the specific mechanisms of hypothermia are only partly understood.
      Evidence supports the concept that therapeutic cooling suppresses multiple
      extracellular death signals, including intracellular pathways of apoptotic and
      necrotic cell death and inappropriate microglial activation. Thus, the optimal
      depth of induced hypothermia is that which effectively suppresses the cell death
      pathways after hypoxia-ischaemia, but without inhibiting recovery of the cellular
      environment. Thus mild hypothermia needs to be continued until the cell
      environment has recovered until it can actively support cell survival. This
      review highlights that key survival cues likely include the inter-related
      restoration of neuronal activity and growth factor release. This working model
      suggests that interventions that target overlapping mechanisms, such as
      anticonvulsants, are unlikely to materially augment hypothermic neuroprotection.
      We suggest that further improvements are most likely to be achieved with late
      interventions that maximise restoration of the normal cell environment after
      therapeutic hypothermia, such as recombinant human erythropoietin or stem cell
      therapy.

PMID- 29660117
TI  - Polymorphisms of genes involved in inflammation and blood vessel development
      influence the risk of varicose veins.
AB  - Heredity plays an important role in the etiology of varicose veins (VVs).
      However, the genetic basis underlying this condition remains poorly understood.
      Our aim was to replicate top association signals from genome-wide association
      studies (GWASs) for VVs of lower extremities using 2 independent datasets-our
      sample of ethnic Russian individuals (709 cases and 278 controls) and a large
      cohort of British residents from UK Biobank (10 861 cases and 397 594 controls).
      Associations of polymorphisms rs11121615, rs6712038, rs507666, rs966562,
      rs7111987, rs6062618, and rs6905288 were validated in the UK Biobank individuals
      at a Bonferroni-corrected significance level. In Russian cohort, only rs11121615
      reached a nominal significance level of P < .05. Results of original GWAS and
      replication studies were combined by a meta-analysis, and polymorphisms listed
      above as well as rs111434909 and rs4463578 passed a genome-wide significant
      threshold. Notably, the majority of these polymorphisms were located within or
      near genes involved in vascular development and remodeling, and regulation of
      inflammatory response. Our results confirm the role of these polymorphisms in
      genetic susceptibility to VVs and indicate the revealed genomic regions as good
      candidates for further fine-mapping studies and functional analysis. Moreover,
      our findings implicate inflammation and abnormal vascular architecture in VVs
      pathogenesis.

PMID- 29660116
TI  - A novel histochemistry assay to assess and quantify focal cytochrome c oxidase
      deficiency.
AB  - Defects in the respiratory chain, interfering with energy production in the cell,
      are major underlying causes of mitochondrial diseases. In spite of this, the
      surprising variety of clinical symptoms, disparity between ages of onset, as well
      as the involvement of mitochondrial impairment in ageing and age-related diseases
      continue to challenge our understanding of the pathogenic processes. This
      complexity can be in part attributed to the unique metabolic needs of organs or
      of various cell types. In this view, it remains essential to investigate
      mitochondrial dysfunction at the cellular level. For this purpose, we developed a
      novel enzyme histochemical method that enables precise quantification in fresh
      frozen tissues using competing redox reactions which ultimately lead to the
      reduction of tetrazolium salts and formazan deposition in cytochrome c oxidase
      deficient mitochondria. We demonstrate that the loss of oxidative activity is
      detected at very low levels - this achievement is unequalled by previous
      techniques and opens up new opportunities for the study of early disease
      processes or comparative investigations. Moreover, human biopsy samples of
      mitochondrial disease patients of diverse genotypic origins were used and the
      successful detection of COX-deficient cells suggests a broad application for this
      new method. Lastly, the assay can be adapted to a wide range of tissues in the
      mouse and extends to other animal models, which we show here with the fruit fly,
      Drosophila melanogaster. Overall, the new assay provides the means to quantify
      and map, on a cell-by-cell basis, the full extent of COX deficiency in tissues,
      thereby expending new possibilities for future investigation. (c) 2018 The
      Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of
      Pathological Society of Great Britain and Ireland.

PMID- 29660118
TI  - Effects of high-power ultrasound on microflora, enzymes and some quality
      attributes of a strawberry drink.
AB  - BACKGROUND: The objective of the present work was to study the effect of high
      power ultrasound (HPU) on the microflora, enzymes and some quality attributes of
      a strawberry drink and to provide a theoretical basis for strawberry drink
      processing conducive to the development of more nutritious and healthier
      strawberry drinks. RESULTS: Fresh strawberry drink was subjected to HPU treatment
      at 20 kHz (242, 605 and 968 W cm-2 ) for 2, 4, 6, 8 and 10 min in an ice bath.
      Results showed that polyphenol oxidase (PPO), pectin methyl esterase (PME) and
      beta-glucosidase activities were decreased by 44.90, 89.11 and 84.71%
      respectively at 968 W cm-2 for 10 min. Lower L*, a* and b* values and higher
      browning degree (BD) were observed in HPU-treated samples, resulting in a
      significant increase in DeltaE value (P < 0.05). HPU treatment caused loss of
      viscosity and turbidity, while total soluble solids (TSS) and pH of the
      strawberry drink were stable. Total phenol content and antioxidant capacity
      increased while anthocyanin content decreased compared with untreated samples.
      Total aerobic bacteria (TAB) and molds and yeasts (M&Y) were reduced by 2.07 and
      1.13 log10 cycles respectively at 968 W cm-2 for 10 min. CONCLUSIONS: HPU can
      effectively achieve the effect of pasteurization and maintain the nutrients of
      strawberry drink. (c) 2018 Society of Chemical Industry.

PMID- 29660122
TI  - Significance of Pharmacogenomics in Precision Medicine.
AB  - Precision medicine-a term widely used in modern medicine-emphasizes the goal to
      overcome still existing limitations of therapeutic interventions by tailoring
      medical treatments to individual patient characteristics. Pharmacogenetics was
      one of the first scientific approaches taking molecular biomarkers into
      consideration of diagnostics and therapeutic decisions. This issue of Clinical
      Pharmacology & Therapeutics on the significance of pharmacogenomics inprecision
      medicine discusses the ongoing challenges on different levels. Access and usage
      of clinical biobanks, gain of specific information of medication from electronic
      health records, and tools to combine clinical and molecular information in order
      to develop advanced clinical decision support are subjects of numerous research
      initiatives. Implementation in clinical routine, however, remains the subject of
      evaluation of clinical- and cost-effectiveness, so far.

PMID- 29660123
TI  - A new species of Hemibrycon (Characiformes, Characidae, Stevardiinae) from the
      upper Magdalena River basin in Colombia.
AB  - Hemibrycon iqueima sp. nov., is described from small streams in the Magdalena
      drainage at the foothills of the western slope of the Eastern Cordillera of the
      Colombian Andes, Suarez municipality, Tolima Department, Colombia. The new
      species is distinguished from its congeners in the Magdalena-Cauca River basin by
      a combination of characters related to snout-anal-fin origin length, head length,
      dorsal-pectoral fin distance, dorsal-fin-hypural distance, postorbital distance,
      orbital diameter, snout length, number of total vertebrae, pre-dorsal scales,
      scale rows between anal-fin origin and lateral line, number of branched rays of
      the anal fin, maxillary teeth number and number and arrangement of hooks on the
      branched rays of the pectoral and dorsal fins. In addition, the validity of this
      species is supported by previous molecular analyses that included specimens of
      the new species that had been erroneously identified. Phylogenetic relationships
      between the new species and congeners from Pacific coast basins are discussed.

PMID- 29660124
TI  - Age and growth of the endemic Xingu River stingray Potamotrygon leopoldi
      validated using fluorescent dyes.
AB  - Between 2003 and 2005, vertebrae of 151 Xingu River Potamotrygon leopoldi
      (Potamotrygonidae) (75 males and 76 females) were analysed to derive a growth
      curve for this species. The disc width (WD ) was significantly different between
      sexes, with females measuring 149-700 mm WD and males 109-500 mm WD . The average
      percentage error for vertebrae readings of the whole sample was 2.7%. The
      marginal increment ratio (RMI ) showed an increasing trend with the highest value
      in November, decreasing from December on. The majority of vertebrae displaying
      RMI zero, occurred in September, but the annual periodicity of ring deposition
      throughout the year was not conclusive. Tetracycline (TCN) injected specimens
      were held in captivity for 13 months and displayed a fluorescent mark in
      vertebrae confirming a yearly periodicity of band pair formation with the
      translucent ring deposited in September-October. The Akaike information criterion
      (AIC) showed that, among the seven models considered, the best fit was obtained
      for the von Bertalanffy modified with W0 (where W0 = WD at birth) for both sexes.
      Growth parameters for females were: W0 = 149 mm; Winfinity = 763.06 mm; k = 0.12
      year- 1 , whereas for males: W0 = 109 mm; Winfinity = 536.4 and k = 0.22 year-1 .
      Maximal ages were 7.2 years in males and 14.3 years in females. The species shows
      sexual dimorphism expressed in the growth pattern, size at maturity, longevity
      and asymptotic sizes. Concern for sustainability is raised due to the
      construction of the Belo Monte Hydroelectric Power Plant (2015 and 2016) in the
      State of Para causing changes to the habitat of this species, which is endemic to
      the Xingu River and two of its tributaries.

PMID- 29660125
TI  - Study of virgin olive oil clarification by settling under dynamic conditions.
AB  - BACKGROUND: Vertical centrifugation is the main method for virgin olive oil (VOO)
      clarification. However, in recent years, settling tanks are also being used to
      clarify the oils from decanters. They can operate under static or dynamic
      conditions. In this work, vertical centrifugation and settling under dynamic
      conditions for VOO clarification and their effects on VOO characteristics were
      compared. RESULTS: VOO quality parameters were not affected by the clarification
      systems studied. The vertical centrifugal separator (VCS) showed higher
      clarification efficiency, giving clarified oils with higher phenol content and
      better sensory characteristics. VOOs clarified by dynamic settling showed notable
      losses of phenols and worse sensory characteristics, since the tank purge system
      was not efficient, with most of the impurities remaining in the tanks.
      CONCLUSION: The VCS with minimal water addition is a quick operation with low
      water consumption and is a better option to produce VOOs of improved quality,
      especially in terms of longer shelf life and preservation of positive sensory
      notes. (c) 2018 Society of Chemical Industry.

PMID- 29660126
TI  - GrigoraSNPs: Optimized Analysis of SNPs for DNA Forensics.
AB  - High-throughput sequencing (HTS) of single nucleotide polymorphisms (SNPs)
      enables additional DNA forensic capabilities not attainable using traditional STR
      panels. However, the inclusion of sets of loci selected for mixture analysis,
      extended kinship, phenotype, biogeographic ancestry prediction, etc., can result
      in large panel sizes that are difficult to analyze in a rapid fashion. GrigoraSNP
      was developed to address the allele-calling bottleneck that was encountered when
      analyzing SNP panels with more than 5000 loci using HTS. GrigoraSNPs uses a
      MapReduce parallel data processing on multiple computational threads plus a novel
      locus-identification hashing strategy leveraging target sequence tags. This tool
      optimizes the SNP calling module of the DNA analysis pipeline with runtimes that
      scale linearly with the number of HTS reads. Results are compared with SNP
      analysis pipelines implemented with SAMtools and GATK. GrigoraSNPs removes a
      computational bottleneck for processing forensic samples with large HTS SNP
      panels.

PMID- 29660127
TI  - On the thermal behavior of protein isolated from different legumes investigated
      by DSC and TGA.
AB  - BACKGROUND: Pea, lentil, faba bean, chickpea and bean proteins are potentially
      renewable raw materials for bioplastic production that can be obtained from
      agricultural waste. Plastics are usually processed under heating, and thus
      thermal stability is a mandatory requirement for the application. In this study,
      the thermal behavior of several legume protein isolates at different purity
      degrees was investigated. RESULTS: The thermal stability of proteins extracted
      from legumes was maximum for chickpeas and minimum for beans and decreased with
      decreasing protein purity in the range 30-88%. A similar dependence on purity was
      observed for the glass transition temperature. On the contrary, the denaturation
      temperature was found not to depend on sample purity and origin and was lower
      than the degradation temperature only in the case of protein samples with purity
      higher than 60%. CONCLUSION: Proteins from legumes are suitable to produce
      thermoplastic biopolymeric materials if isolated at purity higher than 60%. In
      fact, under this circumstance, they can be denaturized without degrading and thus
      are suitable for extrusion processing. (c) 2018 Society of Chemical Industry.

PMID- 29660128
TI  - Multi-factor accelerated aging of neutral pudding packed in retort pouches
      determined by instrumental and fluorescence techniques.

PMID- 29660129
TI  - Midwives' and women's views on accessing dental care during pregnancy: an
      Australian qualitative study.
AB  - BACKGROUND: Maternal behaviours during pregnancy are likely to play a significant
      role in the development of dental caries in children. Although midwives are well
      placed to discuss oral health and provide information to women, dental attendance
      by women during pregnancy is minimal. This study aimed to explore midwives'
      experience of facilitating pregnant women's access to dental care and to document
      women's experience of receiving dental information and care during pregnancy.
      METHODS: Focus groups with midwives and telephone interviews with women who were
      referred to Monash Health Dental Services were conducted to explore their
      perspectives and experiences. The qualitative data was thematically analysed.
      RESULTS: Three focus groups with 13 midwives and telephone interviews with eight
      women who recently gave birth were conducted. Three key themes were identified:
      maternal oral health knowledge; barriers to accessing dental information and care
      during pregnancy; and suggested recommendations. CONCLUSIONS: This study
      highlighted the barriers that exist for midwives to discuss oral health with
      women and refer women to dental care, and women's experiences of accessing dental
      care during pregnancy. Ongoing collaboration between the maternity and dental
      services is required to strengthen midwives' knowledge, confidence and practise
      in supporting women to access dental care during pregnancy.

PMID- 29660131
TI  - Hats Off to the Editorial Board.

PMID- 29660130
TI  - Impact of Listeria Inoculation and Aerated Steam Sanitization on Volatile
      Emissions of Whole Fresh Cantaloupes.
AB  - : Rapid methods to detect bacterial pathogens on food and strategies to control
      them are needed to mitigate consumer risk. This study assessed volatile emissions
      from whole cantaloupe melons (Cucumis melo) as an indicator of Listeria
      contamination and in response to steam vapor decontamination. Cantaloupe were
      inoculated with Listeria innocua, a nonpathogenic surrogate for L. monocytogenes,
      then exposed to 85  degrees C steam for 240 s (4 min) followed by rapid chilling
      and storage for 0, 7, 10, or 14 days at 4, 7, or 10  degrees C. Volatile
      emissions from whole melons were collected on Carbopack B/Carboxen 1000 headspace
      collection tubes and analyzed by gas chromatography-mass spectroscopy following
      thermal desorption. Introduction of L. innocua to cantaloupe rind resulted in a
      reduction of aromatic compound emission. However, this response was not unique to
      Listeria contamination in that steam vapor treatment also reduced emission of
      these compounds. As well, steam vapor treatment diminished the number of viable
      Listeria and indigenous microflora while causing physiological injury to melon
      rind. Heat treatment had no significant effects on flesh firmness, color,
      titratable acidity, or soluble solids, but the production of typical aroma
      volatiles during postharvest ripening was inhibited. No unique volatile compounds
      were detected in Listeria contaminated melons. While changes in volatile
      emissions were associated with Listeria inoculation, they could not be
      differentiated from heat treatment effects. Results indicate that volatile
      emissions cannot be used as a diagnostic tool to identify Listeria contamination
      in whole cantaloupe melons. PRACTICAL APPLICATION: The detection of pathogen
      contamination on fresh produce is a continuing challenge. Using a nondestructive
      screening method, the presence of surrogate Listeria innocua on fresh whole
      cantaloupes was shown to alter the emissions of aromatic volatiles from whole
      cantaloupes. However, these altered emissions were not found to be unique to
      Listeria spp. and therefore cannot be used as a definitive indicator of Listeria
      contamination.

PMID- 29660132
TI  - A Comparison of Temporal Dominance of Sensation (TDS) and Quantitative
      Descriptive Analysis (QDATM) to Identify Flavors in Strawberries.
AB  - : Temporal dominance of sensations (TDS) is a rapid descriptive method that
      offers a different magnitude of information to traditional descriptive analysis
      methodologies. This methodology considers the dynamic nature of eating, assessing
      sensory perception of foods as they change throughout the eating event. Limited
      research has applied the TDS methodology to strawberries and subsequently
      validated the results against Quantitative Descriptive Analysis (QDATM). The aim
      of this research is to compare the TDS methodology using an untrained consumer
      panel to the results obtained via QDATM with a trained sensory panel. The trained
      panelists (n = 12, minimum 60 hr each panelist) were provided with six strawberry
      samples (three cultivars at two maturation levels) and applied QDATM techniques
      to profile each strawberry sample. Untrained consumers (n = 103) were provided
      with six strawberry samples (three cultivars at two maturation levels) and
      required to use TDS methodology to assess the dominant sensations for each sample
      as they change over time. Results revealed moderately comparable product
      configurations produced via TDS in comparison to QDATM (RV coefficient = 0.559),
      as well as similar application of the sweet attribute (correlation coefficient of
      0.895 at first bite). The TDS methodology however was not in agreement with the
      QDATM methodology regarding more complex flavor terms. These findings support the
      notion that the lack of training on the definition of terms, together with the
      limitations of the methodology to ignore all attributes other than those
      dominant, provide a different magnitude of information than the QDATM
      methodology. PRACTICAL APPLICATION: A comparison of TDS to traditional
      descriptive analysis indicate that TDS provides additional information to QDATM
      regarding the lingering component of eating. The QDATM results however provide
      more precise detail regarding singular attributes. Therefore, the TDS methodology
      has an application in industry when it is important to understand the lingering
      profile of products. However, this methodology should not be employed as a
      replacement to traditional descriptive analysis methods.

PMID- 29660133
TI  - Response to "On the Reverse Stability Kinetics of Meat Pigment Oxidation in
      Aqueous Extract from Fresh Beef".

PMID- 29660134
TI  - On the Reverse Stability Kinetics of Meat Pigment Oxidation in Aqueous Extract
      from Fresh Beef.

PMID- 29660136
TI  - Posttraumatic Stress Disorder and Diminished Criminal Responsibility as "New
      Evidence" in Criminal Revision Procedures.
AB  - Posttraumatic stress disorder (PTSD) may affect victims of crime, but may also be
      reported by offenders. In the postappeal phase, offenders may claim to suffer
      from chronic PTSD and argue that this indicates diminished criminal
      responsibility at the time the index crime was committed. As members of a Dutch
      criminal cases review commission, we recently encountered two cases in which PTSD
      was presented as new evidence that would justify a reopening of the case. In this
      article, we argue that such claims are problematic in that clinical decision
      making resulting in a PTSD diagnosis adheres to quite different standards than
      those dictating forensic fact-finding. The two cases illustrate the difference
      between criminal and clinical fact-finding.

PMID- 29660137
TI  - Olfactory gene expression in migrating adult sockeye salmon Oncorhynchus nerka.
AB  - Expression of 12 olfactory genes was analysed in adult sockeye salmon
      Oncorhynchus nerka nearing spawning grounds and O. nerka that had strayed from
      their natal migration route. Variation was found in six of these genes, all of
      which were olfc olfactory receptors and had lower expression levels in salmon
      nearing spawning grounds. The results may reflect decreased sensitivity to natal
      water olfactory cues as these fish are no longer seeking the correct migratory
      route. The expression of olfactory genes during the olfactory-mediated spawning
      migration of Pacific salmon Oncorhynchus spp. is largely unexplored and these
      findings demonstrate a link between migratory behaviours and olfactory plasticity
      that provides a basis for future molecular research on salmon homing.

PMID- 29660138
TI  - Orthodontic thermoformed retainers: a two-arm laboratory study into post
      fabrication outcomes.
AB  - BACKGROUND: Retainers are commonly used to maintain post-orthodontic occlusion
      stability. We aimed to determine post-fabrication thickness and thinning rate of
      thermoformed retainers. METHODS: Forty-eight retainers were fabricated from
      polyethylenterepthalat-glycol copolyester or polypropylene blanks, using vacuum-
      or pressure-thermoforming. Retainer thickness was measured at multiple locations.
      RESULTS: Thinning rate had a broad range: the mid-labial incisor region of 1 mm
      polyethylenterepthalat-glycol copolyester pressure-thermoformed mandibular
      retainers had the greatest thinning rate (68.25 +/- 8.26%) and smallest mean post
      fabrication thickness (0.32 +/- 0.08 mm). Polyethylenterepthalat-glycol
      copolyester retainers were 0.11 mm thinner than polypropylene (P=0.0222), and
      polypropylene retainers were 0.21 mm thicker, when pressure-thermoformed
      (P<0.0001). The interaction of manufacturing method and material used, and tooth
      type, explained over a third of the variability in the post-fabrication thickness
      of these retainers. Maxillary retainers made from 1 mm blanks were 0.04 mm
      thicker in the incisor region compared with the molar region (P=0.0492).
      CONCLUSIONS: Thermoformed retainers do no thin uniformly against individual teeth
      and have variable intra- and inter-arch post-fabrication thicknesses. There is no
      clear benefit in using a specific type of thermoforming machine or material for
      increasing post-fabrication thickness or reducing thinning rate. Blank thickness
      and tooth morphology influence these outcomes.

PMID- 29660139
TI  - Swimming performance of 12 Schizothoracinae species from five rivers.
AB  - A series of stepped velocity tests were carried out in a Brett-type swimming
      respirometer and the overall range in swimming performance for 12
      Schizothoracinae species was measured. The relative critical swimming speed Ucrit
      and burst speed Uburst decreased with body length, while absolute Ucrit and
      Uburst increased with body length. Ucrit increased with temperature up to
      approximately 15 degrees  C and then decreased. Species with a high Ucrit also
      displayed a higher Uburst .

PMID- 29660140
TI  - Time course of the photochemical reflectance index during photosynthetic
      induction: its relationship with the photochemical yield of photosystem II.
AB  - Time courses of photochemical reflectance index (PRI) of an attached cucumber
      leaf during a dark-light transition were compared with those of photochemical
      yields of photosystem II (YII ) to discuss the feasibility of PRI imaging for
      estimating the efficiency of photosynthetic light use. YII and PRI were
      simultaneously evaluated with a pulse-amplitude modulation chlorophyll
      fluorometer and a low-cost imaging system consisting of digital cameras and band
      pass filters, respectively. YII decreased immediately after the transition and
      then increased under various photon flux densities. Although PRI exhibited
      delayed time courses with respect to YII under low light conditions, PRI
      decreased monotonically under high light conditions. There was no correlation
      between YII and the changes in PRI (DeltaPRI) immediately after the transition
      but YII was correlated with DeltaPRI under the steady-state photosynthesis. These
      results indicate that the use of PRI to estimate YII under fluctuating light
      based on the regression obtained at steady state can overestimate YII . The
      imaging system was also applied to evaluate the spatial PRI distribution within a
      leaf. While PRI of leaf areas that remained untreated, or had been treated with
      H2 O again, first dropped and then rose under low light and monotonically
      decreased under high light conditions, leaf areas treated with inhibitor
      (dichlorophenyl dimethylurea) did not exhibit any changes. It is likely that the
      inhibitor suppressed lumen acidification, which triggers a decrease in PRI. It
      was suggested that YII of leaves with malfunctions in the photosynthetic electron
      transport can be overestimated by the PRI-based estimation.

PMID- 29660142
TI  - Use of digoxin in atrial fibrillation: One step further in the mortality
      controversy from the AFFIRM study.
AB  - BACKGROUND: Whether there is a causal association between digoxin and mortality
      among patients with atrial fibrillation (AF), with or without congestive heart
      failure (HF), has been controversial; in particular, two prior analyses of data
      from the Atrial Fibrillation Follow-up Investigation of Rhythm Management
      (AFFIRM) trial have yielded conflicting results. We sought to investigate how
      digoxin impacts mortality, in the full AFFIRM cohort and for various subgroups,
      by applying marginal structural modeling (MSM) to AFFIRM data. METHODS: MSM is a
      newer statistical approach, which estimates causal association in the absence of
      randomization. MSM more effectively accounts for time-varying treatment and
      mitigates potential biases, in contrast to the two statistical approaches used in
      prior analyses of the AFFIRM data. RESULTS: Among 4,060 patients in AFFIRM, 660
      (16.3%) died during follow-up. Digoxin was associated with significantly higher
      mortality in the full cohort (estimated hazard ratio [HR] 1.33, 95% confidence
      interval [CI] 1.11-1.60, P  =  0.002) and in 3,121 patients without HF (HR 1.36,
      95% CI 1.07-1.72, P  =  0.011). There was a trend toward higher mortality with
      digoxin in 939 patients with HF (HR 1.29, 95% CI 0.96-1.72, P  =  0.090).
      Associations were nonsignificant in 463 patients with HF and left ventricular
      ejection fraction (EF) >=40% and in 155 patients with EF <=30%. CONCLUSIONS:
      Digoxin is associated with significantly increased mortality among AFFIRM
      patients collectively, as determined by MSM statistical methodology. However, the
      impact of digoxin among AFFIRM patients with coexisting HF is inconclusive.

PMID- 29660141
TI  - Carbonic anhydrase is not a relevant nitrite reductase or nitrous anhydrase in
      the lung.
AB  - KEY POINTS: Carbonic anhydrase (CA) inhibitors such as acetazolamide inhibit
      hypoxic pulmonary vasoconstriction (HPV) in humans and other mammals, but the
      mechanism of this action remains unknown. It has been postulated that carbonic
      anhydrase may act as a nitrous anhydrase in vivo to generate nitric oxide (NO)
      from nitrite and that this formation is increased in the presence of
      acetazolamide. Acetazolamide reduces HPV in pigs without evidence of any NO
      generation, whereas nebulized sodium nitrite reduces HPV by NO formation;
      however; combined infusion of acetazolamide with sodium nitrite inhalation did
      not further increase exhaled NO concentration over inhaled nitrite alone in pigs
      exposed to alveolar hypoxia. We conclude that acetazolamide does not function as
      either a nitrous anhydrase or a nitrite reductase in the lungs of pigs, and
      probably other mammals, to explain its vasodilating actions in the pulmonary or
      systemic circulations. ABSTRACT: The carbonic anhydrase (CA) inhibitors
      acetazolamide and its structurally similar analogue methazolamide prevent or
      reduce hypoxic pulmonary vasoconstriction (HPV) in dogs and humans in vivo, by a
      mechanism unrelated to CA inhibition. In rodent blood and isolated blood vessels,
      it has been reported that inhibition of CA leads to increased generation of
      nitric oxide (NO) from nitrite and vascular relaxation in vitro. We tested the
      physiological relevance of augmented NO generation by CA from nitrite with
      acetazolamide in anaesthetized pigs during alveolar hypoxia in vivo. We found
      that acetazolamide prevents HPV in anaesthetized pigs, as in other mammalian
      species. A single nebulization of sodium nitrite reduces HPV, but this action
      wanes in the succeeding 3 h of hypoxia as nitrite is metabolized and excreted.
      Pulmonary artery pressure reduction and NO formation as measured by exhaled gas
      concentration from inhaled sodium nitrite were not increased by acetazolamide
      during alveolar hypoxia. Thus, our data argue against a physiological role of
      carbonic anhydrase as a nitrous anhydrase or nitrite reductase as a mechanism for
      its inhibition of HPV in the lung and blood in vivo.

PMID- 29660143
TI  - Disseminated Kaposi sarcoma with epithelioid morphology in an HIV/AIDS patient: A
      previously unreported variant.
AB  - Kaposi sarcoma is an oligoclonal HHV-8-driven vascular proliferation that was
      first described by a Viennese dermatologist Dr Moritz Kaposi. The disease has
      been seen in different clinical-epidemiological settings with a wide morphologic
      spectrum. We report a 52-year-old Caucasian man with HIV/AIDS and Kaposi sarcoma
      who presented with dyspnea and pleural effusion. He reported numerous tender
      subcutaneous nodules developing over the past few months on his chest, back and
      abdomen. An excisional biopsy of one of the nodules was performed. Touch preps
      revealed malignant cells in clusters. Microscopically, the neoplasm appeared
      undifferentiated with an epithelioid morphology, and involved the dermis and
      subcutaneous fat. Despite the medical history, Kaposi sarcoma was not considered
      foremost in the differential diagnosis. The malignant cells were positive for
      vimentin and negative for S100 protein, keratin AE1/3, CK7, CK20, napsin A, TTF-1
      and synaptophysin. Additional stains revealed positivity for HHV-8, CD31 and D2
      40, supporting the diagnosis of Kaposi sarcoma. Kaposi sarcoma has been well
      described with many variants that may cause diagnostic difficulty. An epithelioid
      variant has not been reported and consequently, may cause misinterpretation of an
      otherwise well-known entity that may become life threatening if appropriate
      treatment is not initiated in a timely manner.

PMID- 29660144
TI  - In situ growth of Zr-based metal-organic framework UiO-66-NH2 for open-tubular
      capillary electrochromatography.
AB  - The high stability and other properties of Zr(IV)-based metal organic
      frameworks(MOFs) make it a promising choice for chromatographic separation, while
      the application in open-tubular capillary electrochromatography (OT-CEC)
      separation has not been explored yet. Herein, we report the first example of the
      in-situ growth of UiO-66-NH2 onto the capillary for open-tubular capillary
      electrochromatography. UiO-66-NH2 consists of ZrCl4 and 2-amino-1,4
      benzenedicarboxylic acid, which is highly porous and stable in a variety of
      solvents. The prepared UiO-66-NH2 modified capillary was characterized by
      scanning electron microscopy (SEM) and Fourier transform infrared spectra (FT
      IR), and the results confirmed the successful growth of the UiO-66-NH2 . The
      baseline separation of chlorobenzenes, phenoxyacids and two groups of phenols was
      achieved owing to the combined interaction of pi-pi interaction, hydrophobic
      interaction, molecular sieve effect, electrophoretic migration and hydrogen
      bonding interaction etc. Besides, the prepared capillaries showed good
      reproducibility, with relative standard deviations (RSDs) for intra-day, inter
      day and column-to-column runs in the range of 1.38-2.60%, 3.39-4.05%, and 3.47
      5.03%, respectively. Our work indicates Zr(IV)-based MOFs are promising materials
      as stationary phase in CEC separation.

PMID- 29660145
TI  - Hyperpolarized magnetic resonance in chemistry.

PMID- 29660146
TI  - Stability of two layers dielectric-electrolyte microflow subjected to an
      alternating external electric field.
AB  - The stability of the electroosmotic flow of the two-phase system electrolyte
      dielectric with a free interface in the microchannel under an external electric
      field is examined theoretically. The mathematical model includes the Nernst-Plank
      equations for the ion concentrations. The linear stability of the 1D
      nonstationary solution with respect to the small, periodic perturbations along
      the channel, is studied. Two types of instability have been highlighted. The
      first is known as the long-wave instability and is connected with the distortion
      of the free charge on the interface. In the long-wave area, the results are in
      good agreement with the ones obtained theoretically and experimentally in the
      literature. The second type of instability is a short-wave and mostly connected
      with the disturbance of the electrolyte conductivity. The short-wave type of
      instability has not been found previously in the literature and constitutes the
      basis and the strength of the present work. It is revealed that with the increase
      of the external electric field frequency, the 1D flow is stabilized. The
      dependence of the flow on the other parameters of the system is qualitatively the
      same as for the constant electric field.

PMID- 29660147
TI  - Free radical-initiated peptide sequencing (FRIPS)-based cross-linkers for
      improved peptide and protein structure analysis.
AB  - Free radical-initiated peptide sequencing (FRIPS) has recently been introduced as
      an analytical strategy to create peptide radical ions in a predictable and
      effective way by collisional activation of specifically modified peptides ions.
      FRIPS is based on the unimolecular dissociation of open-shell ions and yields
      fragments that resemble those obtained by electron capture dissociation (ECD) or
      electron transfer dissociation (ETD). In this review article, we describe the
      fundamentals of FRIPS and highlight its fruitful combination with chemical cross
      linking/mass spectrometry (MS) as a highly promising option to derive
      complementary structural information of peptides and proteins. FRIPS does not
      only yield exhaustive sequence information of cross-linked peptides, but also
      defines the exact cross-linking sites of the connected peptides. The development
      of more advanced FRIPS cross-linkers that extend the FRIPS-based cross-linking/MS
      approach to the study of large protein assemblies and protein interaction
      networks can be eagerly anticipated.

PMID- 29660148
TI  - In vivo effect of a TLR5 SNP (C1205T) on Salmonella enterica serovar Typhimurium
      infection in weaned, specific pathogen-free Landrace piglets.
AB  - Toll-like receptor 5 is a pattern-recognition receptor for bacterial flagellin.
      We previously reported that a single nucleotide polymorphism (SNP) of swine TLR5,
      C1205T, impairs recognition of Salmonella typhimurium (ST) flagellin and ethanol
      killed Salmonella Choleraesuis (SC). In the present study, weaned, specific
      pathogen-free (SPF) Landrace piglets with CC, CT or TT genotypes were orally
      infected with ST (L-3569 strain) to determine the effect of this specific SNP on
      ST infection in vivo. Eighteen ST-infected piglets (six each with CC, CT, or TT)
      exhibited fever and diarrhea for 1 week after infection. TT piglets had the
      longest duration of fever. TT piglets had the greatest mean diarrhea score during
      the experimental period, followed by CT and CC piglets. Fecal ST shedding was
      greater in CT and TT pigs than CC pigs from 2 days after infection. Serum
      haptoglobin concentration increased in ST-infected piglets and to greater extents
      in CT and TT pigs than CC pigs. Daily weight gain was lower in infected pigs,
      particularly TT piglets, than control pigs. To the best of our knowledge, this
      study is the first to demonstrate that impairment of TLR recognition affects pig
      susceptibility to disease in vivo. Thus, piglets with the T allele of swine TLR5
      (C1205T) exhibit impaired resistance to ST infection. Furthermore, elimination of
      the T allele of this SNP from Landrace pigs would lead to enhancement of their
      resistance to ST infection.

PMID- 29660149
TI  - Study of supercritical CO2 extraction of tamarillo (Cyphomandra Betacea) seed oil
      containing high added value compounds.
AB  - In the present investigation, the extraction of tamarillo seed oil was conducted
      using supercritical carbon dioxide (SC-CO2), under different conditions of
      pressure (20-38.1 MPa) and temperature (40-64 degrees C). In order to determine
      the effect that these extraction parameters have over the yield and composition
      of the oil, a central composite design was used. The optimum yield was 21.07%
      obtained at 38.1 MPa and 64 degrees C. The fatty acids of the tamarillo seed oil
      obtained with SC-CO2 were identified: linoleic (70.12%), oleic (16.18%), palmitic
      (9.68%), stearic (2.12%), linolenic (1.70%), and palmitoleic (0.23%). Other
      components, such as squalene (2.96-19.75 mg/mL), beta-sitosterol (2.05-3.68
      mg/mL), cycloartenol (1,23-2.81 mg/mL) dihydrolanosterol (0.28-0.70 mg/mL)
      sterols and gamma-tocopherol (0.89-2.10 mg/mL) were also noted. The extraction
      kinetic was studied at 27.5 MPa -50 degrees C and 38.1 MPa -64 degrees C. The
      semi-empirical model of Sovova et al. [24] described 99.21% of the experimental
      behavior of extraction kinetics. High yields of tamarillo seed oil, as well as
      its unique composition of unsaturated fatty acids and minor components, show the
      potential for its application in the food, cosmetic, and pharmaceutical
      industries.

PMID- 29660150
TI  - Sample preparation in foodomic analyses.
AB  - Representative sampling and adequate sample preparation are key factors for
      successful performance of further steps in foodomic analyses, as well as for
      correct data interpretation. Incorrect sampling and improper sample preparation
      can be sources of severe bias in foodomic analyses. It is well known that both
      wrong sampling and sample treatment cannot be corrected anymore. These, in the
      past frequently neglected facts, are now taken into consideration, and the
      progress in sampling and sample preparation in foodomics is reviewed here. We
      report the use of highly sophisticated instruments for both high-performance and
      high-throughput analyses, as well as miniaturization and the use of laboratory
      robotics in metabolomics, proteomics, peptidomics, and genomics.

PMID- 29660152
TI  - Incidence of pediatric atopic dermatitis following thymectomy: A Danish register
      study.

PMID- 29660151
TI  - Hangover in Post-College-Aged Drinkers: Psychometric Properties of the Hangover
      Symptom Scale (HSS) and the Hangover Symptom Scale-Short Form (HSS-5).
AB  - BACKGROUND: Alcohol hangovers have been found to be a common and costly
      consequence of alcohol misuse. However, there is only limited psychometric
      support for instruments to accurately measure hangovers beyond the college-age
      years. This study investigated the psychometric properties of the Hangover
      Symptom Scale (HSS) and the Hangover Symptom Scale-Short Form (HSS-5) including
      the internal consistency, convergent and discriminant validity, construct
      validity, and the measurement invariance of these scales between light and heavy
      drinkers, individuals with a positive and negative family history of alcohol use
      disorder (AUD), and men and women in a post-college-aged sample. The association
      of the HSS and HSS-5 with alcohol use problems was also tested. METHODS:
      Participants were 294 nonalcoholic light and heavy social drinkers (age range 21
      to 35 years; 57.8% male) enrolled in the Chicago Social Drinking Project. They
      completed the HSS as part of a take-home packet completed outside of the
      laboratory. The psychometric properties of the HSS and HSS-5 were tested.
      RESULTS: Stronger psychometric support was found for the HSS-5 relative to the
      full HSS. While both measures demonstrated strong internal consistency
      reliability, convergent and discriminant validity, and an association with
      alcohol use problems, only the HSS-5 showed construct validity as determined by
      confirmatory factor analysis. Further, only the HSS-5 showed measurement
      invariance between men and women, light and heavy drinkers, and individuals with
      a positive and negative family history of AUD. CONCLUSIONS: This was the first
      study to examine the psychometric properties of the HSS and HSS-5 in a post
      college-aged sample and the first to investigate the measurement invariance of
      these measures as a function of sex, drinking history, and family history of AUD.
      This study supports the use of the HSS-5 as a reliable and valid brief measure of
      frequency of hangover symptoms.

PMID- 29660153
TI  - Subchondral bone microdamage accumulation in distal metacarpus of Thoroughbred
      racehorses.
AB  - BACKGROUND: Microdamage accumulation leads to subchondral bone injury and/or
      fracture in racehorses. An understanding of this process is essential for
      developing strategies for injury prevention. OBJECTIVES: To quantify subchondral
      bone microdamage in the third metacarpal bone of Thoroughbred racehorses at
      different stages of the training cycle. STUDY DESIGN: Cross-sectional. METHODS:
      Bone blocks from the palmar aspect of the medial condyles of third metacarpal
      bones from 46 racing Thoroughbred horses undergoing post-mortem were examined
      with micro computed tomography (microCT) to detect calcified microcracks, and
      light microscopy to quantify bulk stained microcracks. Racing and training
      histories were obtained for comparison with microdamage data using regression
      modelling. RESULTS: Subchondral bone microcracks were observed in all bones with
      at least one method. Microdamage grade was greater in older horses, levelling-off
      for horses 5 years and older (quadratic term P = 0.01), and with lower bone
      material density in the parasagittal groove (P = 0.02). Microcrack density was
      higher in older horses (P = 0.004), and with higher bone volume fraction (BV/TV)
      in the parasagittal groove in horses in training (interaction effect, P = 0.01)
      and lower in horses resting from training (P = 0.02). MAIN LIMITATIONS: Cross
      sectional data only. Incomplete detection of microdamage due to the limits of
      resolution of microCT and lack of three-dimensional imaging with microscopy.
      Multicollinearity between variables that indicated career progression (e.g. age,
      number of career starts, duration of training period) was detected. CONCLUSIONS:
      Fatigue damage in the distal metacarpal subchondral bone is common in
      Thoroughbred racehorses undergoing post-mortem and appears to accumulate
      throughout a racing career. Reduced intensity or duration of training and racing
      and/or increased duration of rest periods may limit microdamage accumulation.
      Focal subchondral bone sclerosis indicates the presence of microdamage.

PMID- 29660154
TI  - Local mepivacaine before castration of horses under medetomidine isoflurane
      balanced anaesthesia is effective to reduce perioperative nociception and
      cytokine release.
AB  - BACKGROUND: In horses castration with primary intention healing is usually
      performed under balanced inhalation anaesthesia. To optimise analgesia, the use
      of local anaesthesia was tested. OBJECTIVES: To investigate the effect of local
      mepivacaine before castration with first intention healing under balanced
      medetomidine-isoflurane anaesthesia and flunixin meglumine, morphine analgesia on
      perioperative cytokine levels and pain in horses. STUDY DESIGN: Prospective
      blinded clinical study. METHODS: Twenty stallions were randomly assigned to
      control or mepivacaine groups. Flunixin meglumine was administered before
      sedation with medetomidine and followed by ketamine/diazepam intravenously
      (i.v.). Anaesthesia was maintained with isoflurane and 3.5 MUg/kg per hour
      medetomidine. Mepivacaine horses were given mepivacaine 2% (3.5 mL SC, 1 mL/100
      kg intrafunicularly, 2 mL/100 kg intratesticularly) on each side. For recovery,
      horses were given 2 MUg/kg medetomidine i.v. and 0.1 mg/kg morphine i.m. and oral
      phenylbutazone (0.02 mg/kg q12h) for post-operative analgesia. One hour before
      premedication and 4, 8 and 24 h post-incision, pain was scored with three
      different pain scales (Equine Utrecht University Scale for Facial Assessment of
      Pain, Horse Grimace Scale, Equine Utrecht University Scale for Composite Pain
      Assessment) and plasma cytokines (interleukin-6 and tumour necrosis factor alpha)
      were measured. Data were analysed using repeated measures ANOVA, linear
      regression and unpaired t-test, significance level P<=0.05. RESULTS: Horses in
      both groups showed a significant increase in pain scores and cytokines compared
      to baseline. Post-operatively the mepivacaine group exhibited significantly lower
      pain scores and cytokine levels. Mean heart rate during anaesthesia was
      significantly lower in the mepivacaine group compared to control group (28.8 +/-
      1 and 33.2 +/- 1.7 respectively). Otherwise there were no differences between the
      groups. MAIN LIMITATIONS: The decision to provide additional analgesia was based
      on the attending surgeon's assessment rather than a standardised rescue analgesia
      plan based on pain scores. The study was only conducted for 24 h post-castration
      and complications were not recorded. CONCLUSION: Local mepivacaine before
      castration with primary wound closure improved anaesthesia quality, attenuated
      post-operative increases in cytokines and reduced post-operative pain despite
      balanced anaesthesia with multimodal analgesia in control horses.

PMID- 29660155
TI  - Thread/paper- and paper-based microfluidic devices for glucose assays employing
      artificial neural networks.
AB  - This paper describes the fabrication of and data collection from two microfluidic
      devices: a microfluidic thread/paper based analytical device (MUTPAD) and 3D
      microfluidic paper-based analytical device (MUPAD). Flowing solutions of glucose
      oxidase (GOx), horseradish peroxidase (HRP), and potassium iodide (KI), through
      each device, on contact with glucose, generated a calibration curve for each
      platform. The resultant yellow-brown color from the reaction indicates oxidation
      of iodide to iodine. The devices were dried, scanned, and analyzed yielding a
      correlation between yellow intensity and glucose concentration. A similar
      procedure, using an unknown concentration of glucose in artificial urine, is
      conducted and compared to the calibration curve to obtain the unknown value.
      Studies to quantify glucose in artificial urine showed good correlation between
      the theoretical and actual concentrations, as percent differences were <=13.0%.
      An ANN was trained on the four-channel CMYK color data from 54 MUTPAD and 160
      MUPAD analysis sites and Pearson correlation coefficients of R = 0.96491 and
      0.9739, respectively, were obtained. The ANN was able to correctly classify 94.4%
      (51 of 54 samples) and 91.2% (146 of 160 samples) of the MUTPAD and MUPAD
      analysis sites, respectively. The development of this technology combined with
      ANN should further facilitate the use of these platforms for colorimetric
      analysis of other analytes.

PMID- 29660156
TI  - Evaluation of symptomatic esophagogastric junction outflow obstruction.
AB  - BACKGROUND AND AIM: Esophagogastric junction outflow obstruction (EGJOO) may be
      due to anatomical abnormalities, but it is unclear how to evaluate them after
      high-resolution manometry. We aimed to determine (i) clinical and high-resolution
      manometry parameters differentiating anatomical EGJOO from functional EGJOO, (ii)
      investigations chosen and yield for anatomical EGJOO, and (iii) clinical outcomes
      of functional EGJOO. METHODS: Medical records of consecutive patients with
      symptomatic EGJOO from February 2012 to December 2015 were reviewed. EGJOO was
      defined as anatomical if investigations identified a macroscopic or microscopic
      pathology accounting for EGJOO. RESULTS: Forty of 292 (13.7%) had EGJOO, of which
      6/40 (15%) had anatomical EGJOO (two PPI-responsive esophageal eosinophilia, two
      infiltrating cancers, and two external compressions). Anatomical EGJOO was more
      likely to present with dysphagia (100% vs 29.4%, P = 0.001) and less likely with
      regurgitation (0% vs 41.2%, P = 0.05). Anatomical EGJOO had higher frequencies of
      premature contraction (50% vs 5.9%, P = 0.003) and lower mean values of distal
      latency (5.6 +/- 1.3 vs 6.7 +/- 1.2, P = 0.004). Computed tomography scans
      revealed 50% (3/6) of etiologies of anatomical EGJOO. Approximately, 73.5%
      (25/34) of patients with functional EGJOO had spontaneous resolution of their
      symptoms. One underwent pneumatic dilatation with symptom resolution while
      remaining eight with persistent symptoms were attributed to gastroesophageal
      reflux disease. CONCLUSION: Anatomical causes are present in 15% of EGJOO.
      Evaluation is warranted especially in patients presenting with dysphagia.
      Esophageal biopsies, barium swallows, computed tomography scans, and endoscopic
      ultrasound are complementary in EGJOO evaluation. In patients with non
      obstructive symptoms and no anatomical etiologies, monitoring for spontaneous
      resolution is an option.

PMID- 29660157
TI  - Two Types of Vigilance Are Essential to Effective Hazard Management: Maintaining
      Both Together Is Difficult.
AB  - Flexibility and adaptability are key capabilities for coping with persistent and
      pervasive uncertainties. The systematic organization of these capabilities is
      often called "adaptive management"; it is key to effective hazard management and
      important in risk governance. Vigilance is a requirement for effective
      adaptation. However, two distinct types of vigilance are necessary. Type 1
      vigilance directly supports adaptive management. It is vigilance when you know
      what you are looking for: warning signals, filling gaps in knowledge, making sure
      that systems are working, etc. Vigilance of another sort, type 2 vigilance, is
      needed to address the surprises and institutional failures that are not part of
      orderly adaptive planning. Type 2 vigilance is vigilance when you don't know what
      to look for: observing and reflecting on confusing signals, anomalies,
      unacknowledged responsibilities, and surprises. The two types of vigilance
      require different institutional capabilities, and hence may work against each
      other in practice. Type 1 vigilance requires focus and a strong, knowledge-based
      organizing framework. Type 2 vigilance, in contrast, requires defocusing and a
      questioning approach to both observations and concepts. This dilemma, coupled
      with demands for flexibility, is a severe challenge for organizations. There are
      a variety of actions and arrangements at various levels of societal organization
      that could maintain and enhance vigilance in managing hazards. Necessary,
      however, is the societal and institutional recognition that vigilance of more
      than one type is an essential part of hazard management and the commitment to
      follow through. Maintaining vigilance requires effort and must be an ongoing
      process.

PMID- 29660159
TI  - Cannabis and anticancer drugs: societal usage and expected pharmacological
      interactions - a review.
AB  - Cannabis is a plant that has been used for centuries to relieve a wide range of
      symptoms. Since the 1960s, interest in medical research into this plant has grown
      steadily. Already very popular for recreational use, a growing number of
      consumers not accustomed to using cannabis for psychoactive purposes have begun
      to use it as an alternative or complement to mainstream pharmaceutical medicines.
      The principal unsubstantiated or 'social' uses of cannabis are based mainly on
      data that is at best controversial, but usually not scientifically proven. The
      aim of this review was to identify the scientific basis and reasons that lead
      patients with cancer to consume cannabis, and also to identify whether there is a
      risk of interaction between cannabis and anticancer medicines through drug
      transporters (P-glycoprotein and other ATP-binding cassette superfamily members)
      Cytochromes P450 (3A, 1A, 2B, 2C, 2D families...) and glucuronyl transferases.

PMID- 29660158
TI  - Cutaneous presentation preceding acute myeloid leukemia with CD4+/CD56+
      expression misdiagnosed as a blastic plasmocytoid dendritic cell neoplasm: A case
      report.
AB  - Acute myeloid leukemia (AML) may initially present as cutaneous lesions
      corresponding to blasts involving the skin as the first clinical manifestation
      prior to blood and bone marrow (BM) infiltration. Such presentation is known as
      myeloid leukemia cutis (LC). Blastic plasmocytoid dendritic cell neoplasm (BPDCN)
      is an aggressive tumor derived from the precursors of plasmocytoid dendritic
      cells with cutaneous and BM involvement and leukemic dissemination. Myeloid LC
      and BPDCN may be difficult to distinguish as they share similar clinical and
      histopathological features, in particular AML with monocytic differentiation.
      Nevertheless, the correct diagnosis has to be made to determine adequate and
      effective therapy. Here, we report the case of a 61-year-old woman who presented
      with an AML with MLL rearrangement and CD4+/CD56+ expression presenting as LC and
      that was misdiagnosed as BPDCN. We emphasize that careful and exhaustive analyses
      should be performed to make the correct diagnosis.

PMID- 29660160
TI  - Digital image analysis improves precision of PD-L1 scoring in cutaneous melanoma.
AB  - AIMS: Immune checkpoint inhibitors have become a successful treatment in
      metastatic melanoma. The high response rates in a subset of patients suggest that
      a sensitive companion diagnostic test is required. The predictive value of
      programmed death ligand 1 (PD-L1) staining in melanoma has been questioned due to
      inconsistent correlation with clinical outcome. Whether this is due to predictive
      irrelevance of PD-L1 expression or inaccurate assessment techniques remains
      unclear. The aim of this study was to develop a standardised digital protocol for
      the assessment of PD-L1 staining in melanoma and to compare the output data and
      reproducibility to conventional assessment by expert pathologists. METHODS AND
      RESULTS: In two cohorts with a total of 69 cutaneous melanomas, a highly
      significant correlation was found between pathologist-based consensus reading and
      automated PD-L1 analysis (r = 0.97, P < 0.0001). Digital scoring captured the
      full diagnostic spectrum of PD-L1 expression at single cell resolution. An
      average of 150 472 melanoma cells (median 38 668 cells; range = 733-1 078 965)
      were scored per lesion. Machine learning was used to control for heterogeneity
      introduced by PD-L1-positive inflammatory cells in the tumour microenvironment.
      The PD-L1 image analysis protocol showed excellent reproducibility (r = 1.0, P <
      0.0001) when carried out on independent workstations and reduced variability in
      PD-L1 scoring of human observers. When melanomas were grouped by PD-L1 expression
      status, we found a clear correlation of PD-L1 positivity with CD8-positive T cell
      infiltration, but not with tumour stage, metastasis or driver mutation status.
      CONCLUSION: Digital evaluation of PD-L1 reduces scoring variability and may
      facilitate patient stratification in clinical practice.

PMID- 29660161
TI  - The FGF-23/klotho axis and its relationship with phosphorus, calcium, vitamin D,
      PTH, aldosterone, severity of disease, and outcome in hospitalised foals.
AB  - BACKGROUND: Fibroblast growth factor-23 (FGF-23) and klotho are key regulators of
      vitamin D and parathyroid hormone (PTH) synthesis as well as phosphorus and
      calcium homeostasis; however, information on the FGF-23/klotho axis in healthy
      and hospitalised foals is lacking. OBJECTIVES: The aims of this study were to
      measure serum FGF-23 and klotho concentrations and determine their association
      with serum phosphorus, total calcium (TCa), vitamin D metabolite [25(OH)D,
      1,25(OH)2 D], PTH, and aldosterone concentrations, disease severity, and
      mortality in hospitalised foals. STUDY DESIGN: Prospective, multicentre, cross
      sectional study. METHODS: A total of 91 foals <=72 h old were classified as
      hospitalised (n = 81; 58 septic; 23 sick non-septic [SNS]) and healthy (n = 10).
      Blood samples were collected on admission. Hormone concentrations were determined
      by immunoassays. RESULTS: Serum FGF-23, PTH, phosphorus, and aldosterone
      concentrations were higher while klotho, 25(OH)D, 1,25(OH)2 D, and TCa
      concentrations were lower in septic and SNS compared to healthy foals (P<0.05).
      In hospitalised and septic foals, increased FGF-23 and aldosterone concentrations
      were associated with high phosphorus and PTH but not with TCa and vitamin D
      metabolite concentrations. Hospitalised foals with the highest FGF-23 and lowest
      klotho concentrations were more likely to die (odds ratio (OR): 3.3; 95%
      confidence interval (CI): 1.1-10.3 and OR: 3.1; CI: 1.1-8.0, respectively). MAIN
      LIMITATIONS: Blood gas, ionised calcium, blood culture information not being
      available for many foals, and use of the sepsis score to classify hospitalised
      foals. CONCLUSIONS: Imbalances in the FGF-23/klotho axis may contribute to
      mineral dyshomeostasis and disease progression in critically ill foals. Elevated
      FGF-23 and reduced klotho, together with high phosphorus and PTH concentrations
      suggests FGF-23 resistance. FGF-23 and klotho are good markers of disease
      severity and likelihood of mortality in hospitalised foals. Aldosterone may
      influence phosphorus and PTH dynamics in hospitalised foals. Routine measurement
      of phosphorus concentrations in sick foals is recommended.

PMID- 29660162
TI  - Determinants of amikacin first peak concentration in critically ill patients.
AB  - Amikacin antimicrobial effect has been correlated with the ratio of the peak
      concentration (Cmax ) to the minimum inhibitory concentration. A target Cmax >=
      60-80 mg/L has been suggested. It has been shown that such target is not achieved
      in a large proportion of critically ill patients in intensive care units. A
      retrospective analysis was performed to examine the determinants of Cmax >= 80
      mg/L on the first peak in 339 critically ill patients treated by amikacin. The
      influence of available variables on Cmax target attainment was analyzed using a
      classification and regression tree (CART) and logistic regression. Mean Cmax in
      the 339 patients was 73.0 +/- 23.9 mg/L, with a target attainment rate (TAR, Cmax
      >= 80 mg/L) of 37.5%. In CART analysis, the strongest predictor of amikacin
      target peak attainment was dose per kilogram of lean body weight (dose/LBW). TAR
      was 60.1% in patients with dose/LBW >= 37.8 vs. 19.9% in patients with lower
      dose/LBW (OR = 6.0 (95% CI: 3.6-10.2)). Renal function was a secondary predictor
      of Cmax . Logistic regression analysis identified dose per kilogram of ideal body
      weight (OR = 1.13 (95% CI: 1.09-1.17)) and creatinine clearance (OR = 0.993 (95%
      CI: 0.988-0.998)) as predictors of target peak achievement. Based on our results,
      an amikacin dose >= 37.8 mg/kg of LBW should be used to optimize the attainment
      of Cmax >= 80 mg/L after the first dose in critically ill patients. An even
      higher dose may be necessary in patients with normal renal function.

PMID- 29660163
TI  - Evolution from S3 to S4 States of the Oxygen-Evolving Complex in Photosystem II
      Monitored by Quantum Mechanics/Molecular Mechanics (QM/MM) Dynamics.
AB  - Water oxidation in the early steps of natural photosynthesis is fulfilled by
      photosystem II, which is a protein complex embedded in the thylakoid membrane
      inside chloroplasts. The water oxidation reaction occurs in the catalytic core of
      photosystem II, which consists of a Mn4Ca metal cluster, at which, after the
      accumulation of four oxidising equivalents through five steps (S0-S4) of the Kok
      Joliot cycle, two water molecules are split into electrons, protons, and
      molecular oxygen. In recent years, by combining experimental and theoretical
      approaches, new insights have been achieved into the structural and electronic
      properties of different steps of the catalytic cycle. Nevertheless, the exact
      catalytic mechanism, especially concerning the final stages of the cycle, remains
      elusive and greatly debated. Herein, by means of quantum mechanics/molecular
      mechanics (QM/MM) molecular dynamics simulations, from the structural,
      electronic, and magnetic points of view, the S3 state before and upon oxidation
      has been characterised. In contrast with the S2 state, the oxidation of the S3
      state is not followed by a spontaneous proton-coupled electron-transfer event.
      Nevertheless, upon modelling the reduction of the tyrosine residue in photosystem
      II (TyrZ ) and the protonation of Asp61, spontaneous proton transfer occurs,
      leading to the deprotonation of an oxygen atom bound to Mn1; thus making it
      available for O-O bond formation.

PMID- 29660165
TI  - Usefulness of gastroduodenal biopsy in the differential diagnosis of systemic AH
      amyloidosis from systemic AL amyloidosis.
AB  - AIMS: The aim of this study is to examine the usefulness of gastroduodenal biopsy
      for the detection of immunoglobulin (Ig) heavy-chain amyloid deposition. Ig heavy
      chain amyloidosis (AH amyloidosis) is Ig-related amyloidosis classified together
      with Ig light-chain amyloidosis (AL amyloidosis). Compared with AL amyloidosis,
      patients with AH amyloidosis exhibit a better prognosis and they may not need an
      aggressive treatment. Thus, the accurate diagnosis is essential for management of
      Ig-related amyloidosis patients. For the definite diagnosis of AH amyloidosis,
      biochemical analyses are usually needed. However, these analyses are not widely
      available. Therefore, the characteristic deposition pattern of AH amyloidosis in
      routine histopathological examination of biopsy specimens, such as
      gastrointestinal biopsy, if present, may help in the selection of cases for
      further biochemical analyses. METHODS AND RESULTS: Gastroduodenal biopsy
      specimens obtained from three cases of biochemically confirmed AH amyloidosis and
      21 cases of immunohistochemically confirmed AL amyloidosis were examined, and the
      following distinctive histopathological features of AH amyloidosis were pointed
      out: (i) AH amyloid deposition was detectable with Congo red staining in the
      gastroduodenal biopsy specimens; and (ii) AH amyloid deposition was observed
      characteristically on the capillary wall of duodenal villi (dotted line-like
      deposition in the villi), and this pattern was not observed in AL amyloidosis.
      CONCLUSION: These findings help to select cases for biochemical analyses for
      definite diagnosis of AH amyloidosis, and may lead to the accumulation of cases
      and improve our understanding of systemic AH amyloidosis.

PMID- 29660164
TI  - High-grade PanIN presenting with localised stricture of the main pancreatic duct:
      A clinicopathological and molecular study of 10 cases suggests a clue for the
      early detection of pancreatic cancer.
AB  - AIMS: This study aimed to identify the pathological features of high-grade PanIN
      that presents with imaging-detectable abnormalities. METHODS AND RESULTS: Ten
      cases of isolated, main-duct, high-grade PanIN as the primary clinical
      presentation were identified. All patients presented with stenosis of the main
      pancreatic duct, with two being associated with extensive upstream duct
      dilatation (>5 mm in diameter). Pancreatic juice cytology suggested
      adenocarcinoma in all seven cases examined. In resected specimens, high-grade
      PanIN was present chiefly in the main pancreatic duct, with longitudinal
      extension ranging between 3 and 40 mm in length (median = 18 mm). In four cases,
      in which hypoechoic or hypovascular masses were observed on imaging,
      radiopathology correlations suggested that they represented parenchymal atrophy
      and subsequent fibrosis around affected ducts, but not invasive malignancy. On
      immunohistochemistry, the loss of p16 expression was found in five (50%), p53
      overexpression in two (20%) and loss of SMAD4 expression in none (0%). KRAS
      mutations were detected in nine cases, with two dominant clones being found in
      three by ultrasensitive droplet digital polymerase chain reaction, suggesting the
      genetic heterogeneity of dysplastic cells composing individual lesions. Mutant
      GNAS was also observed in one case. CONCLUSIONS: Isolated high-grade PanIN may
      present with pancreatic duct stenosis. Therefore, intensive investigations
      including pancreatic juice cytology will be required for patients with
      unexplained pancreatic duct stenosis. The abnormal expression of p53 and SMAD4 is
      infrequent, while GNAS may be mutated in premalignant lesions mainly affecting
      the main pancreatic duct, similar to KRAS.

PMID- 29660166
TI  - Lymphomatoid papulosis with folliculotropism, eccrinotropism and neurotropism.
AB  - The histopathological characteristics of lymphomatoid papulosis (LyP) vary.
      Currently, 6 subtypes have been reported, including a new subtype with
      perifollicular infiltration and different degrees of folliculotropism of CD30+
      atypical lymphocytes, known as follicular LyP. However, LyP pathologically
      manifesting with folliculotropism, eccrinotropism and neurotropism has been
      rarely reported. We present a case of LyP showing CD30+ atypical lymphocytes
      around the hair follicle, eccrine gland and nerve fiber, with varying degrees of
      infiltrates. The pathological characteristics of folliculotropism and
      eccrinotropism are often associated with mycosis fungoides (MF). This case
      suggests that differential diagnosis is necessary when atypical lymphocytes
      infiltrate the follicle and eccrine gland. As folliculotropism and eccrinotropism
      can occur in both MF and LyP, it may represent a conceptual intersection between
      the 2 disease processes.

PMID- 29660167
TI  - Microscopy with ultraviolet surface excitation (MUSE): A novel approach to real
      time inexpensive slide-free dermatopathology.
AB  - Traditional histology relies on processing and physically sectioning either
      frozen or formalin-fixed paraffin-embedded (FFPE) tissue into thin slices
      (typically 4-6 MUm) prior to staining and viewing on a standard wide-field
      microscope. Microscopy using ultraviolet (UV) surface excitation (MUSE)
      represents a novel alternative microscopy method that works with UV excitation
      using oblique cis-illumination, which can generate high-quality images from the
      cut surface of fresh or fixed tissue after brief staining, with no requirement
      for fixation, embedding and histological sectioning of tissue specimens. We
      examined its potential utility in dermatopathology. Concordance between MUSE
      images and hematoxylin and eosin (H&E) slides was assessed by the scoring of MUSE
      images on their suitability for identifying 10 selected epidermal and dermal
      structures obtained from minimally fixed tissue, including stratum corneum,
      stratum granulosum, stratum spinosum, stratum basale, nerve, vasculature,
      collagen and elastin, sweat glands, adipose tissue and inflammatory cells, as
      well as 4 cases of basal cell carcinoma and 1 case of pseudoxanthoma elasticum
      deparaffinized out of histology blocks. Our results indicate that MUSE can
      identify nearly all normal skin structures seen on routine H&E as well as some
      histopathologic features, and appears promising as a fast, reliable and cost
      effective diagnostic approach in dermatopathology.

PMID- 29660168
TI  - Risk factors for equine glandular and squamous gastric disease in show jumping
      Warmbloods.
AB  - BACKGROUND: Prevalence of, and risk factors for, equine squamous gastric disease
      (ESGD) are well established. Limited data exists on risk factors for equine
      glandular gastric disease (EGGD). OBJECTIVES: To identify management factors
      associated with EGGD in show jumping Warmbloods in training. A secondary
      objective was to identify management factors associated with ESGD. STUDY DESIGN:
      Cross-sectional. METHODS: Gastroscopies were performed in horses following a 12
      16 h fast. Management questionnaires were collected for each horse. Risk factors
      were determined using multivariable logistic regression modelling. RESULTS:
      Eighty-three horses were included in the final analysis. Exercising >=6 days per
      week increased the odds of EGGD grade >=1/4 (odds ratio [OR] = 3.5; 95%
      confidence interval [CI] 1.2-10.7) compared to less frequent exercise. Currently
      showing increased the risk of EGGD grade >=2/4 (OR = 10.2; 95% CI, 1.04-100),
      while competing at the international level decreased the odds of EGGD grade >=2/4
      (OR = 0.11; 95% CI, 0.01-0.97). Exercise intensity increased the odds of grade
      >=1/4 ESGD (OR = 2.8; 95% CI, 1.03-7.8) and feeding beet pulp decreased odds (OR
      = 0.22; 95% CI, 0.07-0.7). Exercise intensity (OR = 3.8; 95% CI, 1.1-12.8)
      increased the likelihood of grade >=2/4 ESGD and feeding beet pulp decreased the
      odds of grade >=2/4 ESGD (OR = 0.1; 0.02-0.64) respectively. MAIN LIMITATIONS:
      This study used a convenience sample of horses within a relatively small
      (approximately 200 km) geographic radius. The sample size was relatively small,
      particularly within the international competition level group. CONCLUSIONS:
      Training and feeding strategies and competition level appear to influence the
      occurrence of EGGD and ESGD. Prospective studies evaluating the impact of
      training frequency, duration, and intensity on gastric physiology may clarify the
      role of exercise in gastric disease.

PMID- 29660169
TI  - Longevity of anterior resin-bonded bridges: survival rates of two tooth
      preparation designs.
AB  - BACKGROUND: Significant developments have occurred in the design of resin-bonded
      bridges (RBB) over the past two decades. They are commonly used as an alternative
      treatment option for a single missing tooth. The longevity of these bridges needs
      to be further investigated to evaluate long-term outcomes for this option to
      remain relevant. METHODS: A cohort of patients who received anterior resin-bonded
      bridges (ARBB) over two decades was studied retrospectively. Longevity of 206
      ARBB was assessed using Kaplan-Meier probability estimates. The two modified
      tooth preparation designs investigated were: (A) mesial and distal vertical
      grooves only; and (B) one proximal groove adjacent to the pontic and two palatal
      grooves. Age and gender of the patient cohort were also recorded. RESULTS:
      Overall survival rate of ARBB was 98% at 5 years, 97.2% at 10 years, and 95.1%
      from 12 years till 21 years. Survival curves showed minor differences when
      compared for the two designs, age groups and gender of ARBB recipients.
      Differences in the proportion of surviving bridges for design A (95.96%) and
      design B (98.13%) were not statistically significant (Fisher's exact test).
      CONCLUSIONS: Anterior RBB with described tooth preparation designs demonstrate a
      high survival rate.

PMID- 29660170
TI  - Wrestling with the complexity of evaluation for organizations at the boundary of
      science, policy, and practice.
AB  - Boundary organizations are situated between science, policy, and practice and
      have a goal of supporting communication and collaboration among these sectors.
      They have been promoted as a way to improve the effectiveness of conservation
      efforts by building stronger relationships between scientists, policy makers,
      industry, and practitioners (Cook et al. 2013). Although their promise has been
      discussed in theory, the work of and expectations for boundary organizations are
      less defined in practice. Biodiversity conservation is characterized by
      complexity, uncertainty, dissent, and tight budgets, so boundary organizations
      face the challenging task of demonstrating their value to diverse stakeholders.
      We examined the challenges boundary organizations face when seeking to evaluate
      their work and thus aimed to encourage more productive conversations about
      evaluation of boundary organizations and their projects. Although no off-the
      shelf solution is available for a given boundary organization, we identified 4
      principles that will support effective evaluation for boundary organizations:
      engage diverse stakeholders, support learning and reflection, assess contribution
      to change, and align evaluation with assumption and values.

PMID- 29660172
TI  - Predictive accuracy of the Southwest Thames Obstetric Research Collaborative
      (STORK) chorionicity-specific twin growth charts for stillbirth: a validation
      study.
AB  - OBJECTIVE: Twin pregnancy is associated with 2-3 fold increased risk of
      stillbirth compared to singletons. Despite the fact that the growth pattern has
      been shown to differ in twins compared to singletons, it is controversial whether
      twin-specific growth charts should be routinely used. A major goal of prenatal
      ultrasound is to identify fetuses suffering from growth restriction at risk of
      stillbirth. The main aim of this study was to compare the performance of
      chorionicity-specific twin charts with singleton charts, both customized and non
      customized, in the antenatal prediction of small-for-gestational age (SGA)
      stillborn and liveborn fetuses. METHODS: This was a multicenter cohort study
      analyzing data from the Southwest Thames Obstetric Research Collaborative (STORK)
      multiple pregnancy cohort (2000-2009) and a second cohort of twin pregnancies at
      St. George's University Hospital (SGH) (2011-2016). The former cohort was used to
      compare the performance of the twin and non-customized (Poon) singleton charts.
      The latter cohort was used to compare the performance of the twin, customized
      (Gestation Related Optimal Weight [GROW]) and non-customized (Poon) singleton
      charts. The primary outcome was the prediction of SGA cases that were stillborn
      and liveborn in twin pregnancies. The estimated fetal weight (EFW) available from
      the last scan (24 weeks' gestation and onwards) before delivery or demise was
      used to classify the fetuses as SGA (<10th centile, <3rd centile) or appropriate
      for gestational age. The proportions of SGA stillbirths and SGA livebirths
      predicted were calculated using the three different charts. RESULTS: The STORK
      cohort consisted of 1850 dichorionic (DC) and 300 monochorionic (MC) twin
      pregnancies. The SGH cohort consisted of 579 DC and 180 MC twin pregnancies. The
      stillbirth rate in the STORK and SGH cohorts were 1.1% and 1.3%, respectively. In
      those liveborn in the STORK cohort, using a 10th centile cut-off to define SGA,
      the non-customized singleton chart identified a significantly greater proportion
      as SGA compared to the twin chart, regardless of chorionicity (p<0.001). However,
      there was no significant difference between the twin and the non-customized
      singleton charts in regards to in the proportion of stillbirth cases that were
      SGA (p=0.479). In the SGH cohort, the non-customized singleton chart identified
      8.5% of all liveborn fetuses as SGA (<10th centile) compared to 12.8% using the
      customized singleton chart and 7.1% using the twin chart (p=0.005 and p<0.001,
      respectively). However, there was no significant difference among the three
      charts in the proportion of stillbirths identified as SGA, regardless of
      chorionicity (p=0.999). Similar results were obtained when the third centile cut
      off was used to define SGA. CONCLUSIONS: Compared to the STORK chorionicity
      specific twin charts, the customized or non-customized singleton charts
      identified more liveborn fetuses as SGA. However, the three charts identified a
      similar proportion of stillbirth SGA cases. Our preliminary results suggest that
      these twin charts could safely reduce unnecessary medical intervention in twin
      pregnancies. Further research on the topic is needed before clinical
      recommendations can be made.

PMID- 29660174
TI  - Update of Diabetes UK Evidence-Based Nutritional Guidelines for 2018: a
      celebration of two leading journals working together to improve nutritional
      science and dietetic care for people living with diabetes.

PMID- 29660173
TI  - Majority-Rules Effect and Allostery in Molecular Recognition of Calix[4]arene
      Based Triple-Stranded Metallohelicates.
AB  - The triple-stranded metallohelicates 1 a,/1 b-3 a/3 b possessing internal guest
      binding cavities surrounded by calix[4]arene units were synthesized through
      coordination-driven self-assembly. UV/Vis titration experiments verified that the
      metallohelicates encapsulated N-methyl pyridinium cations bearing amino acid
      groups to form host-guest complexes. The guest chirality was transferred to the
      helicity of the helicates through the steric contact between the stereogenic
      center of the amino acid group and the metal cores. The (M) helicity was induced
      when guests the (R)-4--(R)-6 were accommodated within the cavities. The multiple
      guest complexation within the self-assembled helicates 2 a and 3 a displayed
      large positive cooperative effects, indicating that the first guest complexation
      preorganizes the rest of the cavities to facilitate a subsequent guest binding.
      This cooperativity results in the majority-rules effect in the chiral guest
      binding for 2 a and 3 a.

PMID- 29660175
TI  - Redox-Switchable Calix[6]arene-Based Isomeric Rotaxanes.
AB  - Operating molecular machines are based on switchable systems whose components can
      be set in motion in a controllable fashion. The presence of nonsymmetrical
      elements is a mandatory requirement to obtain and demonstrate the
      unidirectionality of motion. Calixarene-based macrocycles have proved to be very
      efficient hosts in the design of oriented rotaxanes and of pseudorotaxanes with
      strict control over the direction of complexation. A series of two-station
      rotaxanes based on bipyridinium-ammonium axles was synthesized and characterized.
      A recently reported supramolecularly assisted strategy for the synthesis of
      different orientational isomers was exploited, and the ammonium unit was
      identified as a proper secondary station for the calixarene. Displacement of the
      macrocycle was triggered by electrochemical reduction of the bipyridinium primary
      station, and it was shown that the shuttling is influenced both by the length of
      the chain of the axle component and by the position of the secondary station with
      respect to the calixarene rims.

PMID- 29660176
TI  - The role of radiotherapy as salvage and/or consolidation treatment in
      relapsed/refractory and high-risk diffuse large B-cell lymphoma.
AB  - OBJECTIVE: Many salvage therapies have been proposed for relapsed/refractory
      (R/R) diffuse large B-cell lymphomas or for consolidation in the case of
      suboptimal response. Radiotherapy (RT) is one modality of salvage therapy, but
      its place is currently not well defined. METHOD: This study reports a
      retrospective review of patients receiving unplanned radiotherapy for R/R diffuse
      large B-cell lymphoma (DLBCL) or primary mediastinal B-cell lymphoma (PMBCL), or
      as consolidation therapy after second-line chemotherapy, treated in our hospital.
      RESULTS: Fifty-one patients with a median age of 53.5 years [19-89] were
      selected. The histologic type was DLBCL in 35 cases (68%), PMBCL in 8 cases
      (16%), and secondary transformed NHL in 8 cases (16%). Median aaIPI was 1 [0-4],
      and 17 patients (33%) had a high tumor burden (bulky disease). Sixteen patients
      (31%) were irradiated for a response considered to be insufficient, 18 patients
      (36%) were refractory, and 17 patients (33%) had relapsed. Patients were
      irradiated with a median dose of 40 Gy [15-44], 29 (57%) by a conformal 3D
      technique and 22 (43%) by tomotherapy. With a median follow-up of 36 months [1.0
      127.8] after irradiation, 5-year progression-free survival (PFS) and overall
      survival (OS) were 62% and 72%, respectively. In multivariate analysis, adverse
      factors associated with PFS and OS in our cohort were age >70 years (HR = 5.06, P
      = .02) and post-RT relapse (HR = 12.24, P = .002), whereas favorable factors were
      number of lines of chemotherapy <3 (HR = 0.02, P = .03) and bulky disease (HR =
      0.02, P = .009). CONCLUSION: Due to its low toxicity and ease of use,
      radiotherapy should therefore remain an available option in patients with R/R
      DLBCL or as consolidation therapy in patients with high-risk disease, mostly in
      patients with chemo-sensitive disease or bulky disease.

PMID- 29660178
TI  - Need for empirical evidence to support use of social license in conservation:
      reply to Garnett et al.

PMID- 29660179
TI  - Social license as an emergent property of political interactions: response to
      Kendal and Ford 2017.

PMID- 29660177
TI  - Severe adverse events by tyrosine kinase inhibitors decrease survival rates in
      patients with newly diagnosed chronic-phase chronic myeloid leukemia.
AB  - OBJECTIVE: This multicenter cooperative study aimed to analyze the adverse events
      (AEs) associated with tyrosine kinase inhibitors (TKIs) used as initial treatment
      for chronic-phase chronic myeloid leukemia (CML-CP) and their impact on outcome.
      METHODS: We retrospectively evaluated 450 patients with CML-CP who received TKIs
      between 2004 and 2014. RESULTS: The 5-year overall survival (OS) and event-free
      survival (EFS) rates were 95.1% and 89.0%, respectively. Patients with
      comorbidities (46.4%) and aged >=60 years (50.4%) at diagnosis had significantly
      inferior OS to those without comorbidities and aged <60. Patients achieved higher
      rates of major molecular response (MMR) at 6 and 12 months after initial
      treatment with dasatinib or nilotinib compared to imatinib, but final MMR rates
      were almost the same. Sixty-six percent of patients required treatment
      modifications from first-line TKI therapy; the main reasons were AEs (48.4%) and
      failure (18%). Grade III-IV AEs in first-line TKI therapy were significantly
      correlated to inferior OS/EFS compared to grade 0-II AEs. CONCLUSION: Although
      long-term outcomes were similar in CML-CP patients treated with each TKI
      regardless of first-line TKI selection, severe AEs in first-line TKI therapy
      decreased their survival rates. Early change in TKIs is recommended, when faced
      with severe AEs of specific TKIs.

PMID- 29660180
TI  - A chromatin loop represses WUSCHEL expression in Arabidopsis.
AB  - WUSCHEL (WUS) is critical for plant meristem maintenance and determinacy in
      Arabidopsis, and the regulation of its spatiotemporal expression patterns is
      complex. We previously found that AGAMOUS (AG), a key MADS-domain transcription
      factor in floral organ identity and floral meristem determinacy, can directly
      suppress WUS expression through the recruitment of the Polycomb group (PcG)
      protein TERMINAL FLOWER 2 (TFL2, also known as LIKE HETEROCHROMATIN PROTEIN 1,
      LHP1) at the WUS locus; however, the mechanism by which WUS is repressed remains
      unclear. Here, using chromosome conformation capture (3C) and chromatin
      immunoprecipitation 3C, we found that two specific regions flanking the WUS gene
      body bound by AG and TFL2 form a chromatin loop that is directly promoted by AG
      during flower development in a manner independent of the physical distance and
      sequence content of the intervening region. Moreover, AG physically interacts
      with TFL2, and TFL2 binding to the chromatin loop is dependent on AG. Transgenic
      and CRISPR/Cas9-edited lines showed that the WUS chromatin loop represses gene
      expression by blocking the recruitment of RNA polymerase II at the locus. The
      findings uncover the WUS chromatin loop as another regulatory mechanism
      controlling WUS expression, and also shed light on the factors required for
      chromatin conformation change and their recruitment.

PMID- 29660181
TI  - Descriptive vs mechanistic scientific approach to study wound healing and its
      inhibition: Is there a value of translational research involving human subjects?
AB  - The clinical field of wound healing is challenged by numerous hurdles. Not only
      are wound-healing disorders complex and multifactorial, but the corresponding
      patient population is diverse, often elderly and burdened by multiple
      comorbidities such as diabetes and cardiovascular disease. The care of such
      patients requires a dedicated, multidisciplinary team of physicians, surgeons,
      nurses and scientists. In spite of the critical clinical need, it has been over
      15 years since a treatment received approval for efficacy by the FDA in the
      United States. Among the reasons contributing to this lack of effective new
      treatment modalities is poor understanding of mechanisms that inhibit healing in
      patients. Additionally, preclinical models do not fully reflect the disease
      complexity of the human condition, which brings us to a paradox: if we are to use
      a "mechanistic" approach that favours animal models, we can dissect specific
      mechanisms using advanced genetic, molecular and cellular technologies, with the
      caveat that it may not be directly applicable to patients. Traditionally,
      scientific review panels, for either grant funding or manuscript publication
      purposes, favour such "mechanistic" approaches whereby human tissue analyses,
      deemed "descriptive" science, are characterized as a "fishing expedition" and are
      considered "fatally flawed." However, more emerging evidence supports the notion
      that the use of human samples provides significant new knowledge regarding the
      molecular and cellular mechanisms that control wound healing and contribute to
      inhibition of the process in patients. Here, we discuss the advances, benefits
      and challenges of translational research in wound healing focusing on human
      subject research.

PMID- 29660182
TI  - Toward a general mixed quantum/classical method for the calculation of the
      vibronic ECD of a flexible dye molecule with different stable conformers:
      Revisiting the case of 2,2,2-trifluoro-anthrylethanol.
AB  - We extend a recently proposed mixed quantum/classical method for computing the
      vibronic electronic circular dichroism (ECD) spectrum of molecules with different
      conformers, to cases where more than one hindered rotation is present. The method
      generalizes the standard procedure, based on the simple Boltzmann average of the
      vibronic spectra of the stable conformers, and includes the contribution of
      structures that sample all the accessible conformational space. It is applied to
      the simulation of the ECD spectrum of (S)-2,2,2-trifluoroanthrylethanol, a
      molecule with easily interconvertible conformers, whose spectrum exhibits a
      pattern of alternating positive and negative vibronic peaks. Results are in very
      good agreement with experiment and show that spectra averaged over all the
      sampled conformational space can deviate significantly from the simple average of
      the contributions of the stable conformers. The present mixed quantum/classical
      method is able to capture the effect of the nonlinear dependence of the rotatory
      strength on the molecular structure and of the anharmonic couplings among the
      modes responsible for molecular flexibility. Despite its computational cost, the
      procedure is still affordable and promises to be useful in all cases where the
      ECD shape arises from a subtle balance between vibronic effects and
      conformational variety.

PMID- 29660183
TI  - Interaction of maternal environment and allelic differences in seed vigour genes
      determines seed performance in Brassica oleracea.
AB  - Seed vigour is a key trait essential for the production of sustainable and
      profitable crops. The genetic basis of variation in seed vigour has recently been
      determined in Brassica oleracea, but the relative importance of the interaction
      with parental environment is unknown. We produced seeds under a range of maternal
      environments, including global warming scenarios. Lines were compared that had
      the same genetic background, but different alleles (for high and low vigour) at
      the quantitative trait loci responsible for determining seed vigour by altering
      abscisic acid (ABA) content and sensitivity. We found a consistent effect of
      beneficial alleles across production environments; however, environmental stress
      during production also had a large impact that enhanced the genetic difference in
      seed performance, measured as germination speed, resistance to controlled
      deterioration and induction of secondary dormancy. Environmental interaction with
      allelic differences in key genes that determine ABA content and sensitivity
      develops a continuity in performance from rapid germination through to failure to
      complete germination, and increasing depths of seed dormancy. The genetic
      environmental interaction revealed provides a robust mechanism of bet-hedging to
      minimize environmental risk during subsequent germination, and this could have
      facilitated the rapid change in seed behaviour (reduced dormancy and rapid
      germination) observed during crop domestication.

PMID- 29660184
TI  - Perception of physical attractiveness when consuming and not consuming alcohol: a
      meta-analysis.
AB  - BACKGROUND AND AIMS: Elucidating why people drink and why drinking can lead to
      negative psychosocial consequences remains a crucial task for alcohol
      researchers. Because drinking occurs typically in social settings, broader
      investigation of the associations between alcohol and social experience is needed
      to advance understanding of both the rewarding and hazardous effects of alcohol
      use. This review aimed to (a) estimate alcohol's relation to the perception of
      others' physical attractiveness and (b) suggest theoretical and methodological
      considerations that may advance the study of this topic. METHODS: Systematic
      review of Scopus and PsycInfo databases was conducted to identify experimental
      and quasi-experimental studies, with either between- or within-subjects designs,
      that assessed attractiveness ratings provided by individuals who had and had not
      consumed alcohol (k = 16 studies, n = 1811). A meta-analysis was conducted to
      evaluate alcohol's aggregate association with physical attractiveness
      perceptions. Separate a priori secondary analyses examined alcohol's associations
      with perception of opposite-sex (k = 12 studies) and same-sex (k = 7 studies)
      attractiveness. RESULTS: The primary analysis indicated that alcohol was related
      significantly to enhanced attractiveness perceptions [d = 0.19, 95% confidence
      interval (CI) = 0.05-0.32, P = 0.01; I2  = 5.28, 95% CI = 0.00-39.32]. Analysis
      of alcohol's association with perception of opposite-sex attractiveness similarly
      yielded a small, significant positive association (d = 0.30, 95% CI = 0.16-0.44,
      P < 0.01; I2  = 17.49, 95% CI = 0.00-57.75). Alcohol's relation to perception of
      same-sex attractiveness was not significant (d = 0.04, 95% CI = -0.18 to 0.26, P
      = 0.71; I2  = 54.08, 95% CI = 0.00-81.66). CONCLUSIONS: Experimental and quasi
      experimental studies suggest that consuming alcohol may have a small effect of
      increasing perceived attractiveness of people of the opposite sex.

PMID- 29660185
TI  - A proposed mechanism for central centrifugal cicatricial alopecia.
AB  - Central centrifugal cicatricial alopecia (CCCA) has an unknown mechanism.
      Analyzing other scarring diseases (lichen planopilaris, fibrotic kidney disease
      and scleroderma) may help to clarify the mechanism of scarring in CCCA. These
      diseases were chosen for comparison due to either their location of disease (skin
      or scalp specifically), or prominence in patients of African descent. Genetics,
      possible triggers, an autoimmune lymphocytic response, and epithelial to
      mesenchymal transition are potentially involved. Possible common pathways in
      scarring diseases and a better understanding of the CCCA mechanism will lead to
      further research into the pathogenesis and potential treatments of CCCA.

PMID- 29660186
TI  - Influence of prenatal diagnosis of abnormally invasive placenta on maternal
      outcome: systematic review and meta-analysis.
AB  - OBJECTIVE: To ascertain the impact of prenatal diagnosis on surgical outcome of
      women affected by abnormally invasive placenta (AIP). METHODS: MEDLINE, EMBASE,
      CINAHL and Cochrane databases were searched. Observed outcomes included:
      gestational age at birth (weeks), amount of blood loss (L), units of red blood
      cells (RBC), platelets (PLT) and fresh frozen plasma (FFP) transfused, length of
      stay in hospital and the intensive care unit (ICU) (days), urinary tract injury
      and infection. Only studies reporting the occurrence of any of the explored
      outcomes in women with a prenatal compared with an intrapartum diagnosis of AIP
      were considered eligible for inclusion. Random-effect head-to-head meta-analyses
      were used to analyze the data. RESULTS: Thirteen studies were included. Women
      with a prenatal diagnosis of AIP had less blood loss during surgery (mean
      difference (MD), -0.87; 95% CI, -1.5 to -0.23), had fewer units of RBC (MD, 
      1.45; 95% CI, -2.9 to -0.04) and FFP (MD, -1.73; 95% CI, -3.3 to -0.2)
      transfused, and delivered earlier (MD, 1.33 weeks; 95% CI, -2.23 to -0.43)
      compared with those with an intrapartum diagnosis. The risk of admission to an
      ICU and length of in-hospital and in-ICU stay were not different between the
      groups. Prenatal diagnosis of AIP was associated with a higher risk of urinary
      tract injury (odds ratio, 2.5; 95% CI, 1.3-4.6), mainly due to the higher
      prevalence of placenta percreta in the group with AIP diagnosed prenatally.
      CONCLUSION: Prenatal diagnosis of AIP is associated with reduced hemorrhagic
      morbidity compared with cases in which such anomalies are detected at delivery.
      Copyright (c) 2018 ISUOG. Published by John Wiley & Sons Ltd.

PMID- 29660187
TI  - Increased flexibility in the use of exogenous lipoic acid by Staphylococcus
      aureus.
AB  - Lipoic acid is a cofactor required for intermediary metabolism that is either
      synthesized de novo or acquired from environmental sources. The bacterial
      pathogen Staphylococcus aureus encodes enzymes required for de novo biosynthesis,
      but also encodes two ligases, LplA1 and LplA2, that are sufficient for lipoic
      acid salvage during infection. S. aureus also encodes two H proteins, GcvH of the
      glycine cleavage system and the homologous GcvH-L encoded in an operon with
      LplA2. GcvH is a recognized conduit for lipoyl transfer to alpha-ketoacid
      dehydrogenase E2 subunits, while the function of GcvH-L remains unclear. The
      potential to produce two ligases and two H proteins is an unusual characteristic
      of S. aureus that is unlike most other Gram positive Firmicutes and might allude
      to an expanded pathway of lipoic acid acquisition in this microorganism. Here, we
      demonstrate that LplA1 and LplA2 facilitate lipoic acid salvage by differentially
      targeting lipoyl domain-containing proteins; LplA1 targets H proteins and LplA2
      targets alpha-ketoacid dehydrogenase E2 subunits. Furthermore, GcvH and GcvH-L
      both facilitate lipoyl relay to E2 subunits. Altogether, these studies identify
      an expanded mode of lipoic acid salvage used by S. aureus and more broadly
      underscore the importance of bacterial adaptations when faced with nutritional
      limitation.

PMID- 29660188
TI  - A critical role for Arabidopsis MILDEW RESISTANCE LOCUS O2 in systemic acquired
      resistance.
AB  - Members of the MILDEW RESISTANCE LOCUS O (MLO) gene family confer susceptibility
      to powdery mildews in different plant species, and their existence therefore
      seems to be disadvantageous for the plant. We recognized that expression of the
      Arabidopsis MLO2 gene is induced after inoculation with the bacterial pathogen
      Pseudomonas syringae, promoted by salicylic acid (SA) signaling, and systemically
      enhanced in the foliage of plants exhibiting systemic acquired resistance (SAR).
      Importantly, distinct mlo2 mutant lines were unable to systemically increase
      resistance to bacterial infection after inoculation with P. syringae, indicating
      that the function of MLO2 is necessary for biologically induced SAR in
      Arabidopsis. Our data also suggest that the close homolog MLO6 has a supportive
      but less critical role in SAR. In contrast to SAR, basal resistance to bacterial
      infection was not affected in mlo2. Remarkably, SAR-defective mlo2 mutants were
      still competent in systemically increasing the levels of the SAR-activating
      metabolites pipecolic acid (Pip) and SA after inoculation, and to enhance SAR
      related gene expression in distal plant parts. Furthermore, although MLO2 was not
      required for SA- or Pip-inducible defense gene expression, it was essential for
      the proper induction of disease resistance by both SAR signals. We conclude that
      MLO2 acts as a critical downstream component in the execution of SAR to bacterial
      infection, being required for the translation of elevated defense responses into
      disease resistance. Moreover, our data suggest a function for MLO2 in the
      activation of plant defense priming during challenge by P. syringae.

PMID- 29660189
TI  - Identification and characterization of doublesex in Bemisia tabaci.
AB  - Bemisia tabaci (Gennadius) is an important agricultural pest with a worldwide
      distribution. Although B. tabaci is known to have a unique haplodiploid
      reproductive strategy, its sex determination mechanism is largely unknown. In
      this study, we cloned the full-length sequence of B. tabaci doublesex (Btdsx) and
      found that Btdsx has 28 splicing isoforms. We found two new splicing isoforms of
      transformer 2 (Bttra2), which encode two proteins. We also confirmed that both
      genes lack sex-specific splicing isoforms. Real-time quantitative PCR analysis
      showed that the expression of Btdsx and Bttra2 is higher in males than in
      females. RNA interference of Bttra2 affected the expression of Btdsx and vice
      versa. Furthermore, silencing of Bttra2 or Btdsx caused malformation of the male
      genitalia (anal style). It did not affect the female phenotype, but reduced the
      expression of vitellogenin gene in females. These results indicate that Btdsx is
      associated with sex determination in B. tabaci and that Btdsx and Bttra2 affect
      each other and are important for male genitalia formation. In addition to
      increasing our understanding of the roles of dsx and tra2 in the sex
      determination of B. tabaci, the results will be useful for studies of sex
      determination in other haplodiploid species.

PMID- 29660190
TI  - Safety and immunogenicity of HBAI20 Hepatitis B vaccine in healthy naive and
      nonresponding adults.
AB  - Approximately 5% of the healthy adult population respond inadequately to the
      commercial recombinant hepatitis B vaccines. As the recombinant vaccines all have
      an aluminium-based adjuvant, we tried to enhance the immune response by adding a
      cytokine-based adjuvant. This new adjuvant AI20, containing 20 MUg recombinant
      human IL-2 attached to 20 MUg aluminium hydroxide, was added to HBVaxPro(c)-10
      MUg (HBAI20). In a double-blind randomized controlled trial (RCT), 24 naive
      subjects were randomized to receive either HBAI20 or commercial HBVaxPro(c)-10
      MUg vaccine. In an open-label study, 10 nonresponders received HBAI20 vaccine.
      All participants received 3 vaccinations (0, 1 and 6 months). In the RCT, the
      occurrence of any adverse events or severe events was similar between the trial
      arms. At month 7, all naive participants were seroprotected; moreover, 92% in the
      HBAI20 group had protective antibodies 10 days after the second vaccination vs
      58% in the HBVaxPro(c)-10 MUg group, P = .16. In the open-label study, no serious
      adverse events were noted. The HBAI20 vaccine was able to elicit protective anti
      HBs titres in 90% of nonresponders, 1 month after the third vaccination.
      According to these results, the new HBAI20 vaccine seems safe, well-tolerated and
      may promote more rapid protection against hepatitis B infection.

PMID- 29660191
TI  - In vivo human sock-mapping validation of a simple model that explains unipolar
      electrogram morphology in relation to conduction-repolarization dynamics.
AB  - INTRODUCTION: The unipolar electrogram (UEG) provides local measures of cardiac
      activation and repolarization and is an important translational link between
      patient and laboratory. A simple theoretical model of the UEG was previously
      proposed and tested in silico. METHOD AND RESULTS: The aim of this study was to
      use epicardial sock-mapping data to validate the simple model's predictions of
      unipolar electrogram morphology in the in vivo human heart. The simple model
      conceptualizes the UEG as the difference between a local cardiac action potential
      and a position-independent component representing remote activity, which is
      defined as the average of all action potentials. UEGs were recorded in 18
      patients using a multielectrode sock containing 240 electrodes and activation
      (AT) and repolarization time (RT) were measured using standard definitions. For
      each cardiac site, a simulated local action potential was generated by adjusting
      a stylized action potential to fit AT and RT measured in vivo. The correlation
      coefficient (cc) measuring the morphological similarity between 13,637 recorded
      and simulated UEGs was cc  =  0.89 (0.72-0.95), median (Q1 -Q3 ), for the entire
      UEG, cc  =  0.90 (0.76-0.95) for QRS complexes, and cc  =  0.83 (0.58-0.92) for T
      waves. QRS and T-wave areas from recorded and simulated UEGs showed cc> 0.89 and
      cc> 0.84, respectively, indicating good agreement between voltage isochrones
      maps. Simulated UEGs accurately reproduced the interaction between AT and QRS
      morphology and between RT and T-wave morphology observed in vivo. CONCLUSIONS:
      Human in vivo whole heart data support the validity of the simple model, which
      provides a framework for improving the understanding of the UEG and its clinical
      utility.

PMID- 29660192
TI  - Characterization of degradation products of macitentan under various stress
      conditions using liquid chromatography/mass spectrometry.
AB  - RATIONALE: Stress testing of a drug candidate is an important step in the drug
      discovery and development process. The presence of degradation products in a drug
      affects the quality as well as the safety and efficacy of drug formulation.
      Hence, it is essential to develop an efficient analytical method which could be
      useful for the separation, identification and characterization of all possible
      degradation products (DPs) of a drug. Macitentan (MT) is an endothelin receptor
      antagonist (ERA) drug used to treat high blood pressure in the lungs.
      Comprehensive stress testing of MT was carried out as per ICH guidelines to
      understand the degradation profile of the drug. METHODS: MT was subjected to
      various stress conditions such as acidic, basic, neutral hydrolysis, oxidation,
      photolysis and thermal conditions; and the resulting degradation products were
      investigated using liquid chromatography/diode-array detection/electrospray
      ionization high-resolution mass spectrometry (LC/DAD/ESI-HRMS) and tandem mass
      spectrometry (MS/MS) techniques. An efficient and simple ultra-high-performance
      liquid chromatography (UHPLC) method has been developed using an Accucore C18
      column (4.6 * 150 mm, 2.6 MUm) using a gradient elution of 5 mM ammonium formate
      and acetonitrile as mobile phases. RESULTS: MT was found to degrade under acid
      and base hydrolysis stress conditions; whereas it was stable under oxidation,
      neutral hydrolysis, thermal and photolytic conditions. MT formed nine DPs (DP1 to
      DP9) and one DP (DP10) under acidic and basic hydrolytic conditions,
      respectively. All the degradation products (DP1 to DP10) were identified and
      characterized by LC/MS/MS in positive ion mode with accurate mass measurements.
      CONCLUSIONS: MT was found to be labile under hydrolytic conditions. The
      structures of the DPs were characterized by appropriate mechanisms. The proposed
      method can be effectively used for the characterization of MT and its DPs.

PMID- 29660193
TI  - Screening of semifluorinated n-alkanes by gas chromatography coupled to
      dielectric barrier discharge ionization mass spectrometry.
AB  - RATIONALE: The potential of an atmospheric pressure ionization source based on a
      dielectric barrier discharge in helium for the hyphenation of gas chromatography
      and mass spectrometry (GC/DBDI-MS) has been demonstrated only recently and for a
      limited range of compounds. Due to its 'soft' ionization properties and the
      possibility to choose from a variety of atmospheric pressure ionization MS
      instruments, GC/DBDI-MS has the potential to be an interesting alternative to
      'classic' GC/MS techniques. METHODS: The hyphenation of GC with DBDI-MS at
      atmospheric pressure is used for the determination of semifluorinated n-alkanes
      in ski wax samples. RESULTS: Different to perfluorinated n-alkanes, which are
      typically detected as [M - F + O]- and [M - F]- , semifluorinated n-alkanes can
      be detected both in positive mode as [M - 3H + nO]+ and [M - H + nO]+ (n = 0, 1,
      2, and 3) ions, as well as in negative mode as a fragment ion representing the
      fluorinated part of the respective semifluorinated n-alkane. The method allowed
      the sensitive detection of semifluorinated n-alkanes with achievable limits of
      detection (LODs) in the single digit pg range injected on column. To examine the
      applicability of the GC/DBDI-MS method, semifluorinated n-alkanes were determined
      in fluorinated ski waxes. Results were confirmed by complimentary GC/electron
      ionization MS measurements. CONCLUSIONS: The unique SFA ionization patterns serve
      for complementary unambiguous identification of semifluorinated n-alkane species
      in positive mode and screening of contained n-alkanes fluorinated chain lengths
      in negative mode.

PMID- 29660194
TI  - BIII 5-Arylsubporphyrins and BIII Subporphine.
AB  - Boron(III) 5-arylsubporphyrins and BIII subporphine are promising precursors for
      functional BIII subporphyrins bearing asymmetric meso-substituents. Herein, we
      report the first synthesis of these molecules. Among many aryl acid chlorides
      examined, 4-nitrobenzoyl chloride gave BIII 5-(4-nitrophenyl)subporphyrin in 10 %
      yield in condensation with triethylamine-tri-N-tripyrromethene-borane. The nitro
      group of this BIII subporphyrin was reduced with NaBH4 to prepare BIII 5
      (aminophenyl)subporphyrin, which was converted into BIII 5-phenylsubporphyrin via
      the corresponding diazonium salt. BIII subporphine was synthesized by
      condensation of triethyl orthoformate with triethylamine-tri-N-tripyrromethene
      borane. Progressive removal of meso-phenyl substituents leads to continuous
      changes in the optical properties, whereas the BIII subporphine deviates from
      this trend in some properties.

PMID- 29660195
TI  - Enantiopure Phospha[1]ferrocenophanes: Textbook Examples of Through-Space Nuclear
      Spin-Spin Coupling.
AB  - Three enantiopure phospha[1]ferrocenophanes (2R ) equipped with either a phenyl,
      an isopropyl, or a tert-butyl group at the bridging phosphorus atom were
      synthesized by a salt-metathesis approach in isolated yields between 52 and 63 %.
      The chirality in these strained sandwich compounds stems from the planar-chiral
      ferrocene moiety, which is symmetrically equipped with two iPr groups adjacent to
      phosphorus. Surprisingly, all three phospha[1]ferrocenophanes show an uncommon
      through-space nuclear 1 H-31 P coupling. As a result of the embedded symmetry,
      these new compounds are ideal examples to differentiate between through-space and
      through-bond coupling mechanisms in NMR spectroscopy.

PMID- 29660196
TI  - Genome-wide Hi-C analysis reveals extensive hierarchical chromatin interactions
      in rice.
AB  - The non-random spatial packing of chromosomes in the nucleus plays a critical
      role in orchestrating gene expression and genome function. Here, we present a Hi
      C analysis of the chromatin interaction patterns in rice (Oryza sativa L.) at
      hierarchical architectural levels. We confirm that rice chromosomes occupy their
      own territories with certain preferential inter-chromosomal associations.
      Moderate compartment delimitation and extensive TADs (Topologically Associated
      Domains) were determined to be associated with heterogeneous genomic compositions
      and epigenetic marks in the rice genome. We found subtle features including
      chromatin loops, gene loops, and off-/near-diagonal intensive interaction
      regions. Gene chromatin loops associated with H3K27me3 could be positively
      involved in gene expression. In addition to insulated enhancing effects for
      neighbor gene expression, the identified rice gene loops could bi-directionally
      (+/-) affect the expression of looped genes themselves. Finally, web-interleaved
      off-diagonal IHIs/KEEs (Interactive Heterochromatic Islands or KNOT ENGAGED
      ELEMENTs) could trap transposable elements (TEs) via the enrichment of silencing
      epigenetic marks. In parallel, the near-diagonal FIREs (Frequently Interacting
      Regions) could positively affect the expression of involved genes. Our results
      suggest that the chromatin packing pattern in rice is generally similar to that
      in Arabidopsis thaliana but with clear differences at specific structural levels.
      We conclude that genomic composition, epigenetic modification, and
      transcriptional activity could act in combination to shape global and local
      chromatin packing in rice. Our results confirm recent observations in rice and A.
      thaliana but also provide additional insights into the patterns and features of
      chromatin organization in higher plants.

PMID- 29660197
TI  - The novel truncated isoform of human manganese superoxide dismutase has a
      differential role in promoting metastasis of lung cancer cells.
AB  - Growing evidences have demonstrated alternative splicing makes great contribution
      to tumor metastasis since multiple protein isoforms from a single gene that often
      display different functions in the cell. Human manganese superoxide dismutase
      (hMnSOD) was revealed dysregulation in progress of tumor metastasis, while the
      effect of hMnSOD isoforms on metastasis remained unclear. In this study, we
      showed a novel truncated hMnSOD isoform hMnSOD183, which lacked 39 amino acids
      compared with hMnSOD222. We expressed two hMnSOD protein isoforms in Escherichia
      coli, respectively, and found that the MnSOD activity of truncated hMnSOD isoform
      was especially weaker. In 95-D cells, mRNA levels of hMnSOD variants and MnSOD
      activity were significantly increased than that in A549 cells. Furthermore, the
      hMnSODc exhibited lower mRNA level than hMnSODa/b in A549 and 95-D cells.
      Additionally, the effects of two isoforms were assessed about cell invasion,
      overexpression of hMnSOD222 but not hMnSOD183 promoted 95-D cells metastasis, and
      hMnSOD knockdown significantly reduced cells invasive behavior. Overexpression of
      hMnSOD isoforms also caused changes of metastasis associated proteins, such as up
      regulation of MMPs, VEGF and Vimentin and down-regulation of E-cadherin.
      Moreover, overexpression of hMnSOD183 had weaker effect on metastasis related
      signaling proteins, such as Akt, JNK and IKKbeta, compared to hMnSOD222. In
      conclusion, our study identified that hMnSOD isoforms induced lung cancer cells
      invasion through Akt-JNK-IKKbeta signaling pathways and the hMnSOD183 isoform
      played a weaker role than hMnSOD222. Characterization of hMnSOD isoforms is
      useful for future investigation on metastasis of lung cancer cells.

PMID- 29660198
TI  - Food advertising on Australian television: Frequency, duration and monthly
      pattern of advertising from a commercial network (four channels) for the entire
      2016.
AB  - AIM: To estimate the frequency, duration and monthly pattern of discretionary
      food advertising on Australian free-to-air television. METHODS: We logged 30 000
      h of television collected in Adelaide during 2016 from one network that has four
      channels. The Australian Guide to Healthy Eating was used to identify
      discretionary foods. Data were examined according to all times, to children's
      peak viewing times (PVTs) and to when C-(children's) rated programmes may be
      broadcast. RESULTS: Of the >800 000 advertisements logged during 2016, 11% were
      for foods (n = 97 837). The most frequently advertised products were: snack foods
      (e.g. crisps), crumbed/battered meats, fast foods/take away meals and sweetened
      beverages. The frequency and duration of discretionary food advertising was 1.7
      times/h and 0.5 min/h respectively at all times. During children's PVTs, the
      frequency and duration of discretionary food advertising was 2.3 times/h and 0.7
      min/h, respectively. When C-rated programmes can be broadcast, the frequency and
      duration of discretionary food advertising was 1.8 times/h and 0.6 min/h,
      respectively. Across the year, discretionary foods ranged between 41% (August)
      and 71% (January) of all food advertising. CONCLUSIONS: Discretionary foods
      dominate food advertising. On average, discretionary food advertising was higher
      during PVTs for children and during the summer school holidays (January).

PMID- 29660199
TI  - Early development of de novo hepatocellular carcinoma after direct-acting agent
      therapy: Comparison with pegylated interferon-based therapy in chronic hepatitis
      C patients.
AB  - Patients with chronic hepatitis C who achieve a sustained viral response after
      pegylated interferon therapy have a reduced risk of hepatocellular carcinoma, but
      the risk after treatment with direct-acting antivirals is unclear. We compared
      the rates of early development of hepatocellular carcinoma after direct-acting
      antivirals and after pegylated interferon therapy. We retrospectively analysed
      785 patients with chronic hepatitis C who had no history of hepatocellular
      carcinoma (211 treated with pegylated interferon, 574 with direct-acting
      antivirals) and were followed up for at least 24 weeks after antiviral treatment.
      De novo hepatocellular carcinoma developed in 6 of 574 patients receiving direct
      acting antivirals and in 1 of 211 patients receiving pegylated interferon. The
      cumulative incidence of early hepatocellular carcinoma development did not differ
      between the treatment groups either for the whole cohort (1.05% vs 0.47%, P =
      .298) or for those patients with Child-Pugh Class A cirrhosis (3.73% vs 2.94%, P
      = .827). Multivariate analysis indicated that alpha-fetoprotein level >9.5 ng/mL
      at the time of end-of-treatment response was the only independent risk factor for
      early development of hepatocellular carcinoma in all patients (P < .0001, hazard
      ratio 176.174, 95% confidence interval 10.768-2882.473) and in patients treated
      with direct-acting agents (P < .0001, hazard ratio 128.402, 95% confidence
      interval 8.417-1958.680). In conclusion, the rate of early development of
      hepatocellular carcinoma did not differ between patients treated with pegylated
      interferon and those treated with direct-acting antivirals and was associated
      with the serum alpha-fetoprotein level at the time of end-of-treatment response.

PMID- 29660200
TI  - Odd-skipped related 1 inhibits lung cancer proliferation and invasion by reducing
      Wnt signaling through the suppression of SOX9 and beta-catenin.
AB  - The odd-skipped related 1 (OSR1) gene encodes a zinc-finger transcription factor.
      The expression and significance of OSR1 in human tumors remains unclear. We found
      that OSR1 was downregulated in lung cancers, and its expression was correlated
      with poor differentiation. Overexpression of OSR1 by OSR1 gene transfection into
      H1299 cells (H1299-OSR1) inhibited the proliferation and invasion of lung cancer
      cells. Knockdown of OSR1 with small interfering (si)RNA against OSR1 in A549
      cells (A549-siOSR1) enhanced the proliferation and invasion of lung cancer cells.
      Western blot analysis showed that the expression level of GSK3beta increased,
      while that of p-GSK3beta, nuclear beta-catenin, cyclin D1, c-Myc and matrix
      metallopeptidase 7 significantly decreased in the H1299-OSR1 cells, and this
      pattern was reversed in the A549-siOSR1 cells compared to that in the control
      cells. Furthermore, upregulation of sex-determining region Y-box 9 (SOX9) by SOX9
      gene transfection increased the expression of beta-catenin, which was inhibited
      by OSR1. The mRNA and protein expression levels of SOX9 and beta-catenin were
      reduced in H1299-OSR1 cells and increased in A549-siOSR1 cells. In conclusion,
      the expression of OSR1 was more reduced in lung cancer tissues than in normal
      lung tissues, and was correlated with poor differentiation. OSR1 downregulated
      the activity of the Wnt signaling pathway by suppressing the expression of SOX9
      and beta-catenin.

PMID- 29660201
TI  - Universal screening for hepatitis C: A needed approach in patients with
      haematologic malignancies.

PMID- 29660203
TI  - Mycobacterium tuberculosis: Active disease and latent infection in a renal
      transplant cohort.
AB  - BACKGROUND: Tuberculosis (TB) is a serious opportunistic infection in renal
      transplant recipients associated with high mortality. Screening and treatment of
      latent Mycobacterium tuberculosis infection (LTBI) offers an opportunity to
      prevent subsequent active disease. METHODS: We retrospectively reviewed the
      records of all adult patients who underwent renal transplantation at our centre
      from 2005 to 2014 to assess current screening practices, the risks for and burden
      of active TB. RESULTS: A total of 660 individuals underwent renal transplantation
      during this period, totalling 3647 person years of follow up. Three patients were
      diagnosed with active TB after renal transplant, resulting in an incidence of 82
      per 100,000 person-years. Of 656 transplant recipients, 102 (15.5%) were born in
      high TB incidence countries and 89 (13.5%) had an interferon gamma release assay
      (IGRA) at any point. Individuals born in high TB risk countries had a much higher
      incidence of active TB (530 per 100,000 person-years). Ten individuals had
      positive IGRA tests, of whom two were treated for active TB, two received
      chemoprophylaxis and six were not treated. CONCLUSIONS: In the absence of formal
      guidelines, IGRA-based screening for LTBI was infrequently performed. Our data
      suggests that screening and treatment of renal transplant recipients born in high
      incidence countries is an important preventive measure.

PMID- 29660204
TI  - Hypoxia induces apoptosis of mouse spermatocyte GC-2 cells through activation of
      autophagy.
AB  - The aim of this study was to investigate the underlying mechanisms of hypoxia
      induced apoptosis of GC-2spd (GC-2) cells. The GC-2 cells were treated with or
      without hypoxia for 12, 24, 48, and 72 h. Apoptosis of GC-2 cells was detected
      using TUNEL and flow cytometry. Fluorescence microscopic was used to observe the
      autophagy of GC-2 cells. Hypoxia-inducible factor-1alpha (HIF-1alpha), apoptosis
      related protein and marker protein of autophagy levels were measured by Western
      blotting. Hypoxia induced apoptosis and autophagy of GC-2 cells, and increased
      expression of HIF-1alpha, LC3-II, Beclin-1, and pro-apoptotic protein, but
      reduced p62 and anti-apoptotic protein level. Meanwhile, hypoxia-induced HIF
      1alpha mediated expression of apoptosis and autophagy-related protein in GC-2
      cell. Furthermore, autophagy regulated hypoxia-induced apoptosis of GC-2 cell.
      Our data suggest that hypoxia induces apoptosis of GC-2 cell by activation of
      autophagy involving activation of the apoptosis signaling pathway under the
      hypoxic condition.

PMID- 29660205
TI  - Thyroid hormones and diabetic nephropathy: an essential relationship to
      recognize.
AB  - AIMS: Although abnormal thyroid hormone metabolism is common in patients with 2
      diabetes mellitus (T2DM) and diabetic nephropathy (DN), the relationship between
      thyroid hormones and DN is unclear and being ignored during the clinical
      practice. This study was aimed to investigate the relationship between thyroid
      hormones and clinicopathologic changes in biopsy-proven DN patients. METHODS: We
      collected clinical and pathological data for 146 biopsy-proven DN patients. The
      patients were divided into four groups: euthyroid group, high-TSH group (SCH),
      low-FT3 group (with normal levels of TSH and FT4), and high-TSH+low-FT3 group
      (with normal levels of FT4). We investigated the clinicopathologic features among
      the four groups. We evaluated the risks of abnormal thyroid hormone levels on DN
      by logistic regression with multivariable adjustments for other risk factors. We
      also performed quarterback and eight-point analyses of TSH and FT3 levels to
      determine their influences on DN. RESULTS: The overt proteinuria (>5 g/24 h)
      (p=0.008) and severity of glomerular lesions (p=0.011) differed between euthyroid
      group and high-TSH group significantly. Moreover, the levels of estimated
      glomerular filtration rate (p=0.019), serum creatinine (p=0.014), and severity of
      glomerular lesions (p=0.003) differed between euthyroid group and low-FT3 group
      significantly. There were also significant differences between high-TSH, low-FT3
      and high-TSH+low-FT3 patients respectively. And respective correlations between
      high-TSH, low-FT3 and renal clinicopathologic changes were found significant
      according to logistic regression analyses. Quarterback and eight-point analyses
      indicated that patients with TSH levels of 4.54-5.67 mU/L had the most severe
      renal clinicopathologic changes, and the severity of renal changes decreased with
      increased FT3 levels. CONCLUSIONS: DN patients with high-TSH and/or low-FT3 had
      more severe proteinuria, renal insufficiency, and glomerular lesions, suggesting
      that regulating thyroid hormones might have a renoprotective effect.

PMID- 29660202
TI  - Molecular biomarkers for uterine leiomyosarcoma and endometrial stromal sarcoma.
AB  - Uterine leiomyosarcoma (u-LMS) and endometrial stromal sarcoma (ESS) are among
      the most frequent soft tissue sarcomas, which, in adults, lead to fatal lung
      metastases and patients have an extremely poor prognosis. Due to their rarity and
      heterogeneity, there are no suitable biomarkers for diagnosis and prognosis,
      although some biomarker candidates have appeared. In 2017, The Cancer Genome
      Atlas (TCGA) Research Network's work on u-LMS has confirmed mutations and
      deletions in RB1, TP53 and PTEN. In addition, whole-exome sequencing of u-LMS has
      confirmed and demonstrated frequent alterations in TP53, RB1, alpha
      thalassemia/mental retardation syndrome X-linked (ATRX) and mediator complex
      subunit 12 (MED12). MED12 is a useful biomarker to diagnose uterine-derived LMS
      and tumors arising from (LM) with a relatively favorable prognosis. TP53 and ATRX
      mutations can be important mechanisms in the pathogenesis of u-LMS and are
      correlated with a poor prognosis. In an update based on the 2014 WHO
      classification, low-grade ESS is often associated with gene rearrangement
      bringing about the JAZF 1-SUZ12 (formerly JAZF1-JJAZ1) fusion gene, whereas high
      grade ESS is associated with the YWHAE-NUTM fusion gene. Low-grade ESS with JAZF1
      rearrangement may correlate with metastasis. However, high-grade ESS with
      metastasis with YWHAE rearrangement shows a relatively favorable prognosis. The
      genetic/molecular genetic aberrations in u-LMS and ESS are reviewed, focusing on
      molecular biomarkers for these primary and metastatic tumors.

PMID- 29660206
TI  - Detection of in vivo hepatitis B virus surface antigen mutations-A comparison of
      four routine screening assays.
AB  - An important requirement for a state-of-the-art hepatitis B surface antigen
      (HBsAg) screening assay is reliable detection of mutated HBsAg. Currently, there
      is a striking shortage of data regarding the detection rates of in vivo HBsAg
      mutations for these clinically important assays. Therefore, we compared the
      detection rates of four commercial HBsAg screening assays using a global cohort
      of 1553 patients from four continents with known HBV genotypes. These samples,
      which represent the broadest spectrum of known and novel HBsAg major hydrophilic
      region (MHR) mutations to date, were analyzed for the presence of HBsAg using the
      Roche Elecsys(r) HBsAg II Qualitative, Siemens ADVIA Centaur XP HBsAg II, Abbott
      Architect HBsAg Qualitative II and DiaSorin Liaison(r) HBsAg Qualitative assays,
      respectively. Of the 1553 samples, 1391 samples could be sequenced; of these,
      1013 (72.8%) carried at least one of the 345 currently known amino acid
      substitutions (distinct HBsAg mutation) in the HBsAg MHR. All 1553 patient
      samples were positive for HBsAg using the Elecsys(r) HBsAg II Qual assay, with a
      sensitivity (95% confidence interval) of 99.94% (99.64%-100%), followed by the
      Abbott Architect 99.81% (99.44%-99.96%), Siemens ADVIA 99.81% (99.44%-99.96%) and
      DiaSorin Liaison(r) 99.36% (98.82%-99.69%) assays, respectively. Our results
      indicate that the Elecsys(r) HBsAg II Qual assay exhibits the highest sensitivity
      among the commercial HBsAg screening assays, and demonstrate that its capacity to
      detect HBV infection is not compromised by HBsAg MHR mutants.

PMID- 29660207
TI  - Randomized, double-blind comparison of aripiprazole/sertraline combination and
      placebo/sertraline combination in patients with major depressive disorder.
AB  - AIM: This study compared the efficacy and safety of aripiprazole/sertraline
      combination (ASC) and placebo/sertraline combination (PSC) in patients with major
      depressive disorder (MDD) who showed an inadequate response to sertraline 100
      mg/day. METHODS: The study comprised a screening period, an 8-week prospective
      treatment (single-blind sertraline 25-100 mg/day) period, and a 6-week double
      blind treatment period. Patients with DSM-5-defined MDD were enrolled. Following
      the prospective treatment, non-responders were randomly assigned to the ASC group
      (aripiprazole 3-12 mg/day/sertraline 100 mg/day) or the PSC group (sertraline 100
      mg/day). The primary efficacy end-point was the mean change in the Montgomery
      Asberg Depression Rating Scale (MADRS) total score from baseline to 6 weeks.
      RESULTS: A total of 412 patients were randomly assigned to either the ASC group
      (n = 209) or the PSC group (n = 203). Mean change in MADRS total score was
      significantly greater in patients with ASC than PSC (-9.2 vs -7.2; P = 0.0070).
      Treatment-emergent adverse events (TEAE) that occurred in >=10% of patients with
      ASC versus PSC were nasopharyngitis (13.4% vs 11.3%) and akathisia (12.9% vs
      3.4%). All TEAE reported in the ASC group were mild or moderate in severity.
      Rates of discontinuations due to TEAE were low in both the ASC (1.9%) and PSC
      (1.5%) groups. There were no notable issues in safety assessments in the ASC
      group compared with the PSC group. CONCLUSION: In patients with MDD who showed an
      inadequate response to treatment with sertraline 100 mg/day, ASC was efficacious
      and well tolerated.

PMID- 29660208
TI  - MiR-340 suppresses the metastasis by targeting EphA3 in cervical cancer.
AB  - MicroRNAs (miRNAs) play key roles in cervical cancer metastasis progression.
      Accumulated evidences have revealed that miRNAs are related to the
      pathophysiological process. However, the role of miR-340 in cervical cancer and
      how it works is still not fully interpreted. Using qRT-PCR to examine the
      expression of miR-340 in cervical cancer tissues. Transwell migration and
      invasion experiments were used to detect the role of miR-340 in migration and
      invasion. Luciferase reporter assay, qRT-PCR, and Western blot were used to
      detect the relationship between miR-340 and EphA3. Using Transwell migration and
      invasion experiments to investigate the role of EphA3 on migration and invasion.
      Restoration expriments were also performed. Western blot was used to assay the
      influence of miR-340 and EphA3 on EMT. We found that miR-340 was downregulated in
      cervical cancer tissues compared with the normal tissues. Transwell migration and
      invasion experiments indicated that overexpression of miR-340 frequently
      inhibited the migration and invasion of cervical cancer cells. EphA3 is a target
      of miR-340, and ectopic expression of EphA3 can promote the migration and
      invasion of cervical cancer cells, whereas restoration of EphA3 in miR-340
      overexpressing cervical cancer cells reversed the suppressive effects of miR-340.
      What's more, the process of migration and invasion which regulated by miR
      340/EphA3 was depended on adjusting the EMT way. These findings indicate that miR
      340 may act as an anti-tumor factor during the process of tumor metastasis
      through targeting EphA3, suggesting that miR-340 might be a potential new
      diagnostic and therapeutic molecule for the treatment of cervical cancer.

PMID- 29660209
TI  - Serum NGAL can act as an early renal safety biomarker during long-term
      nucleos(t)ide analogue antiviral therapy in chronic hepatitis B.
AB  - Tubular renal toxicity is a side-effect of long-term therapy with nucleos(t)ide
      analogue(s) (NA) in chronic hepatitis B (CHB). There are no established surrogate
      markers in plasma of early NA-related toxicity. Neutrophil gelatinase-associated
      lipocalin (NGAL) is a protein produced by tubular cells following renal damage.
      We aimed therefore to retrospectively compare conventional renal markers
      (estimated glomerular filtration rates (eGFR) and urinary protein/creatinine
      ratio uPCR) with a sensitive biomarker (NGAL) in CHB patients on long-term NA
      therapy and assess the ability of new markers to predict NA-related renal
      toxicity (new onset of nonalbumin proteinuria). A total of 192 naive CHB patients
      (median age 41 years, 78% males, 25% HBeAg+, 35% cirrhosis) were NA treated for
      at least 5 years (median 8.34 years, range 5.54-11.1 years). The eGFR and uPCR
      were compared at baseline and last clinical visit with serum NGAL concentrations
      measured by ELISA at same time-points and assessed according to the
      presence/absence of nonalbumin proteinuria at last visit. While baseline and last
      visit eGFR were similar (median:78 vs 84 mL/min), serum NGAL concentrations
      increased during therapy (median:9.4 vs 16.4 ng/mL, P < .05). The proportion of
      patients with proteinuria (uPCR > 15) increased between baseline and last visit
      (4.6% vs 21.4%, P < .05), with 30 (16%) patients having de novo nonalbumin
      proteinuria at last visit. High baseline NGAL concentrations were exclusive to
      patients with de novo nonalbumin proteinuria (median:31.7 vs 7.8 ng/mL, P < .01)
      and baseline NGAL levels >25 mg/mL were predictive of nonalbumin proteinuria at
      last visit (AUROC = 0.813). In conclusion, serum NGAL can act as a surrogate
      marker of early renal injury (de novo nonalbumin proteinuria) in CHB on long-term
      NA therapy.

PMID- 29660210
TI  - Reversible Response of Luminescent Terbium(III)-Nanocellulose Hydrogels to Anions
      for Latent Fingerprint Detection and Encryption.
AB  - Fingerprint fluorescence imaging has become one of the most prominent
      technologies in the field of forensic medicine, but it seldom considers the
      security protection of detection information, which is of great importance in
      modern society. Herein we demonstrate that luminescent TbIII -carboxymethyl
      cellulose (CMC) complex binding aptamer hydrogels that are reversibly responsive
      to ClO- /SCN- can be used for the selective detection, protection, and storage of
      fingerprint information. The imaging information of the fingerprint can be
      quenched and recovered by ClO- /SCN- regulation, respectively, resulting in
      reversible on/off conversion of the luminescence signals for the encryption and
      decryption of multiple levels of information. The present study opens new avenues
      for multilevel imaging, data recording, and security protection of fingerprint
      information with tunable fluorescent hydrogels.

PMID- 29660211
TI  - Effectiveness and cost-effectiveness of interventions targeting harm reduction
      and chronic hepatitis C cascade of care in people who inject drugs: The case of
      France.
AB  - Direct-acting antivirals (DAAs) represent an opportunity to improve hepatitis C
      virus (HCV) care cascade. This combined with improved harm reduction
      interventions may lead to HCV elimination especially in people who inject drugs
      (PWID). We assessed the effectiveness/cost-effectiveness of improvements in harm
      reduction and chronic hepatitis C (CHC) care cascade in PWID in France. We used a
      dynamic model of HCV transmission and CHC natural history and evaluated the
      following: improved needle/syringe programmes-opioid substitution therapies,
      faster diagnosis/linkage to care, earlier treatment initiation, alone and in
      combination among active PWID (mean age = 36). Outcomes were as follows: life
      expectancy in discounted quality-adjusted life years (QALYs); direct lifetime
      discounted costs; incremental cost-effectiveness ratio (ICER); number of
      infections/reinfections. Under the current practice, life expectancy was 15.846
      QALYs, for a mean lifetime cost of ?20 762. Treatment initiation at F0 fibrosis
      stage alone was less effective and more costly than faster diagnosis/linkage to
      care combined with treatment initiation at F0, which increased life expectancy to
      16.694 QALYs, decreased new infections by 37%, with a ICER = ?5300/QALY.
      Combining these interventions with harm reduction improvements was the most
      effective scenario (life expectancy = 16.701 QALYs, 41% decrease in new
      infections) but was not cost-effective (ICER = ?105 600/QALY); it became cost
      effective with higher initial HCV incidence rates and lower harm reduction
      coverage than in our base-case scenario. This study illustrated the high
      effectiveness, and cost-effectiveness, of a faster diagnosis/linkage to care
      together with treatment from F0 with DAAs. This "Test and treat" strategy should
      play a central role both in improving the life expectancies of HCV-infected
      patients, and in reducing HCV transmission.

PMID- 29660212
TI  - Aiming for elimination: Outcomes of a consultation pathway supporting regional
      general practitioners to prescribe direct-acting antiviral therapy for hepatitis
      C.
AB  - To increase access to treatment, the Australian government enabled general
      practitioners (GPs) to prescribe direct-acting antivirals (DAAs) to treat
      hepatitis C virus (HCV)-in consultation with a specialist if inexperienced in HCV
      management. This study describes the establishment and outcomes of a remote
      consultation pathway supporting GPs to treat HCV. Key stakeholders from primary
      and tertiary healthcare services in the Barwon South Western region developed and
      implemented an HCV remote consultation pathway. Pharmaceutical Benefits Schedule
      prescription data were used to evaluate GP DAA prescription 12 months pre-and
      post- pathway implementation. A retrospective review of patients referred for
      remote consultation for 12 months post- pathway inception was undertaken to
      determine the care cascade. HCV treatment initiation by GPs increased after
      implementation of the remote consultation pathway. In the 12-month study period,
      74 GPs referred 169 people for remote consultation; 114 (67%) were approved for
      GP DAA treatment; 48 (28%) were referred for specialist assessment. In total, 119
      (71%) patients commenced DAA; 69 were eligible for SVR12 assessment. Post
      treatment HCV RNA data were available for 52 (75%) people; 37 achieved SVR12; 15
      achieved SVR ranging from week 5 to 11 post-treatment. No treatment failure was
      detected. Collaborative development and implementation of a remote consultation
      pathway has engaged regional GPs in managing HCV. Follow-up post-treatment could
      be improved; however, no treatment failure has been documented. To eliminate HCV
      as a public health threat, it is vital that specialists support GPs to prescribe
      DAA.

PMID- 29660213
TI  - Role of NCoR1 in mitochondrial function and energy metabolism.
AB  - Mitochondrial number and shape are constantly changing in response to increased
      energy demands. The ability to synchronize mitochondrial pathways to respond to
      energy fluctuations within the cell is a central aspect of mammalian homeostasis.
      This dynamic process depends on the coordinated activation of transcriptional
      complexes to promote the expression of genes encoding for mitochondrial proteins.
      Recent evidence has shown that the nuclear corepressor NCoR1 is an essential
      metabolic switch which acts on oxidative metabolism signaling. Here, we provide
      an overview of the emerging role of NCoR1 in the transcriptional control of
      energy metabolism. The identification and characterization of NCoR1 as a central,
      evolutionary conserved player in mitochondrial function have revealed a novel
      layer of metabolic control. Defining the precise mechanisms by which NCoR1 acts
      on energy homeostasis will ultimately contribute towards the development of novel
      therapies for the treatment of metabolic diseases such as obesity and type 2
      diabetes.

PMID- 29660214
TI  - Precore G1896A mutation is associated with reduced rates of HBsAg seroclearance
      in treated HIV hepatitis B virus co-infected patients from Western Africa.
AB  - The nucleotide substitution G1896A on the precore (pc) region has been implicated
      in virological and serological responses during treatment in hepatitis B virus
      (HBV)-infected patients. Whether this mutation affects the therapeutic course of
      HIV-HBV co-infected patients, especially from Western Africa, is unknown. In this
      prospective cohort study, 86 antiretroviral (ARV)-naive HIV-HBV co-infected
      patients from Cote d'Ivoire, initiating ARV-treatment containing lamivudine (n =
      53) or tenofovir (n = 33), had available baseline pc sequences. Association of
      the pcG1896A mutation with time to undetectable HBV-DNA, hepatitis B "e" antigen
      (HBeAg) seroclearance (in HBeAg-positive patients), and hepatitis B surface
      antigen (HBsAg) seroclearance was evaluated using Cox proportional hazards
      regression. At ARV-initiation, median HBV-DNA was 6.04 log10 copies/mL (IQR =
      3.70-7.93) with 97.7% harbouring HBV genotype E. Baseline pcG1896A mutation was
      identified in 51 (59.3%) patients, who were more commonly HBeAg-negative (P <
      .001) and had basal core promotor A1762T/G1764A mutations (P < .001). Patients
      were followed for a median 36 months (IQR = 24-36). Cumulative proportion of
      undetectable HBV-DNA was significantly higher in patients with baseline mutation
      (pcG1896A = 86.6% vs no pcG1896A = 66.9%, P = .04), but not after adjusting for
      baseline HBV-DNA levels and anti-HBV agent (P = .2). No difference in cumulative
      proportion of HBeAg seroclearance was observed between mutation groups (pcG1896A
      = 57.1% vs no pcG1896A = 54.3%, P = .7). Significantly higher cumulative
      proportion of HBsAg seroclearance was observed in patients without this mutation
      (pcG1896A = 0% vs no pcG1896A = 36.9%, P < .001), even after adjusting for
      baseline HBsAg quantification and anti-HBV agent (P < .001). In conclusion,
      lacking the pcG1896A mutation before ARV initiation appeared to increase HBsAg
      seroclearance rates during treatment. The therapeutic implications of this
      mutation need further exploration in this setting.

PMID- 29660216
TI  - The prognostic significance of serum HBeAg on the recurrence and long-term
      survival after hepatectomy for hepatocellular carcinoma: A propensity score
      matching analysis.
AB  - The effects of serum hepatitis B e antigen (HBeAg) on the prognosis of
      hepatocellular carcinoma (HCC) patients after hepatectomy remain controversial.
      Our aim was to explore the prognostic significance of serum HBeAg on the
      prognosis of patients with HCC using a propensity matching model. Between January
      2009 and March 2015, 953 patients with HCC who underwent hepatectomy in West
      China Hospital were analysed. Propensity matching analysis was applied, and
      survival analysis was performed using the Kaplan-Meier method. Risk factors were
      identified by the Cox proportional hazards model. All patients with HCC were
      classified into an HBeAg(-) group (n = 775, 81.3%) or an HBeAg(+) group (n = 178,
      18.7%). Patients with positive serum HBeAg had poorer recurrence-free survival
      and overall survival before and after propensity matching. Similar results were
      found in patients within the Milan criteria. For patients beyond the Milan
      criteria, the HBeAg(+) group had poor overall survival before and after
      propensity matching. In term of recurrence-free survival, there was no
      statistically significant impact after propensity matching (P = .055), although
      there was a trend for HBeAg(+) patient to have reduced recurrence-free survival.
      Positive serum HBeAg, positive HBV-DNA load, largest tumour size, multiple
      tumours, microvascular invasion and a high serum level of preoperative alpha
      fetoprotein were risk factors for recurrence. Our propensity model confirmed that
      positive serum HBeAg had a negative impact on the recurrence and long-term
      survival irrespective of tumour stages. HBeAg seroconversion might be beneficial
      for reducing the rate of recurrence.

PMID- 29660215
TI  - Polygenic risk for psychiatric disorders correlates with executive function in
      typical development.
AB  - Executive functions are a diverse and critical suite of cognitive abilities that
      are often disrupted in individuals with psychiatric disorders. Despite their
      moderate to high heritability, little is known about the molecular genetic
      factors that contribute to variability in executive functions and how these
      factors may be related to those that predispose to psychiatric disorders. We
      examined the relationship between polygenic risk scores built from large genome
      wide association studies of psychiatric disorders and executive functioning in
      typically developing children. In our discovery sample (N = 417), consistent with
      previous reports on general cognitive abilities, polygenic risk for autism
      spectrum disorder was associated with better performance on the Dimensional
      Change Card Sort test from the NIH Cognition Toolbox, with the largest effect in
      the youngest children. Polygenic risk for major depressive disorder was
      associated with poorer performance on the Flanker test in the same sample. This
      second association replicated for performance on the Penn Conditional Exclusion
      Test in an independent cohort (N = 3681). Our results suggest that the molecular
      genetic factors contributing to variability in executive function during typical
      development are at least partially overlapping with those associated with
      psychiatric disorders, although larger studies and further replication are
      needed.

PMID- 29660217
TI  - Photomechanically Induced Magnetic Field Response by Controlling Molecular
      Orientation in 9-Methylanthracene Microcrystals.
AB  - A surfactant-assisted seeded-growth method is used to form single-crystal
      platelets composed of 9-methylanthracene with two different internal molecular
      orientations. The more stable form exhibits a photoinduced twisting, as observed
      previously for 9-methylanthracene microribbons grown by the floating drop method.
      However, the newly discovered elongated hexagonal platelets undergo a
      photoinduced rolling-up and unrolling. The ability of the rolled-up cylindrical
      shape to trap superparamagnetic nanoparticles enables it to be carried along in a
      magnetic field gradient. The new photoinduced shape change, made possible by a
      novel surfactant-assisted crystal growth method, opens up the possibility of
      using light to modulate the crystal translational motion.

PMID- 29660219
TI  - Hepatitis B virus infection in Taiwan: The role of NTCP rs2296651 variant in
      relation to sex.
AB  - Sodium taurocholate cotransporting polypeptide (NTCP) is a functional receptor
      for hepatitis B virus (HBV) infection. NTCP rs2296651 is believed to be an Asian
      specific variant responsible for HBV susceptibility. We investigated the
      relationship between rs2296651 and HBV infection in Taiwan based on
      stratification by gender and menopausal status. We recruited 10 017 Taiwan
      Biobank participants aged 30-70 years with complete genetic data and
      sociodemographic information. Gender-stratified multivariate logistic regression
      models were used to determine the relationship between NTCP variant and HBV
      infection. Among individuals with HBV infection, the genotype frequencies of GG,
      AG and AA in women were 0.85, 0.15 and 0 while those in men were 0.82, 0.18 and
      0, respectively. The multivariate-adjusted odds ratios (OR) of HBV infection were
      0.77 (95% CI 0.59-0.10) in women and 0.98 (95% CI 0.79-1.20) in men. The adjusted
      OR was 0.87 (CI 0.63-1.19) in premenopausal and 0.59 (0.36-0.97) in
      postmenopausal women. We found that genetic variation in the HBV receptor gene
      (NTCP) was significantly associated with a decreased risk of HBV infection in
      Taiwanese women.

PMID- 29660220
TI  - A General, Activator-Free Palladium-Catalyzed Synthesis of Arylacetic and Benzoic
      Acids from Formic Acid.
AB  - A new catalyst for the carboxylative synthesis of arylacetic and benzoic acids
      using formic acid (HCOOH) as the CO surrogate was developed. In an improvement
      over previous work, CO is generated in situ without the need for any additional
      activators. Key to success was the use of a specific system consisting of
      palladium acetate and 1,2-bis((tert-butyl(2-pyridinyl)phosphinyl)methyl)benzene.
      The generality of this method is demonstrated by the synthesis of more than 30
      carboxylic acids, including non-steroidal anti-inflammatory drugs (NSAIDs), under
      mild conditions in good yields.

PMID- 29660218
TI  - Molecular pathogenesis of pancreatic ductal adenocarcinoma: Impact of passenger
      strand of pre-miR-148a on gene regulation.
AB  - We previously used RNA sequencing to establish the microRNA (miRNA) expression
      signature of pancreatic ductal adenocarcinoma (PDAC). We found that both strands
      of pre-miR-148a (miR-148a-5p: the passenger strand and miR-148a-3p: the guide
      strand) were downregulated in cancer tissues. Ectopic expression of miR-148a-5p
      and miR-148a-3p significantly inhibited cancer cell migration and invasion,
      indicating that both strands of pre-miR-148a had tumor-suppressive roles in PDAC
      cells. In silico database and genome-wide gene expression analyses identified a
      total of 15 genes that were putative targets regulated by these miRNAs. High
      expression of miR-148a-5p targets (PHLDA2, LPCAT2 and AP1S3) and miR-148a-3p
      targets (SMA, ENDOD1 and UHMK1) was associated with poor prognosis of patients
      with PDAC. Moreover, knockdown of PHLDA2 expression inhibited cancer cell
      aggressiveness, suggesting PHLDA2 acted as an oncogene in PDAC cells. Involvement
      of the passenger strand of pre-miR-148a (miR-148-5p) is a new concept in cancer
      research. Novel approaches that identify tumor-suppressive miRNA regulatory
      networks in lethal PDAC might provide new prognostic markers and therapeutic
      targets for this disease.

PMID- 29660221
TI  - Brainstem leukoaraiosis independently predicts poor outcome after ischemic
      stroke.
AB  - BACKGROUND AND PURPOSE: Increased supratentorial white matter hyperintensities
      volume (S-WMHV) has been reported to be a predictor of worse outcome in patients
      with acute ischemic stroke (AIS). However, few studies have focused on less
      common locations, such as brainstem white matter hyperintensities (B-WMH), and
      their relationship to S-WMHV. This study aimed to examine whether B-WMH affect
      clinical outcome after AIS or transient ischemic attack (TIA). METHODS: Based on
      magnetic resonance imaging evidence, B-WMH were evaluated in 313 prospectively
      identified patients with AIS/TIA and registered as absent or present.
      Standardized S-WMHV was quantified using a validated volumetric image analysis
      and natural log-transformed (Log_S-WMHV). Poor outcome was defined as a modified
      Rankin Scale score of 3-6 at 3 months after the index event. RESULTS: Brainstem
      white matter hyperintensities were detected in 57 (18.2%) patients. In unadjusted
      analyses for outcome, the presence of B-WMH was associated with worse outcome,
      compared with patients without B-WMH (P = 0.034). In multivariate analysis
      controlling for age, atrial fibrillation, stroke severity, reperfusion therapies
      and Log_S-WMHV, only B-WMH [odds ratio (OR), 2.46; P = 0.021] and stroke severity
      (OR, 1.23; P < 0.001) remained independently associated with unfavourable 90-day
      modified Rankin Scale score. Patients with B-WMH were older (OR, 1.06; P < 0.001)
      and tended to have more hyperlipidaemia (OR, 2.21; P = 0.023) and peripheral
      arterial disease (OR, 2.57; P = 0.031). CONCLUSIONS: Brainstem white matter
      hyperintensities are an independent predictor of poor outcome after AIS/TIA and
      this relationship persists after adjustment for important prognostic factors. Our
      results also show that leukoaraiosis in this location identifies patients with a
      specific risk factor profile, suggesting differences in the underlying
      pathogenesis.

PMID- 29660223
TI  - Direct Aryloxylation/Alkyloxylation of Dialkyl Phosphonates for the Synthesis of
      Mixed Phosphonates.
AB  - A strategy for the direct functionalization strategy of inertial dialkyl
      phosphonates with hydroxy compounds to afford diverse mixed phosphonates with
      good yields and functional-group tolerance has been developed. Mechanistic
      investigations involving both NMR studies and DFT studies suggest that an
      unprecedented highly reactive PV species (phosphoryl pyridin-1-ium salt), a key
      intermediate for this new synthetic transformation, is generated in situ from
      dialkyl phosphonate in the presence of Tf2 O/pyridine.

PMID- 29660222
TI  - Aberrant methylation of EYA4 promotes epithelial-mesenchymal transition in
      esophageal squamous cell carcinoma.
AB  - EYA4, one of the four members of the EYA gene family, is associated with several
      human cancers. However, its biological functions and molecular mechanisms in the
      progression of cancer, particularly in esophageal squamous cell carcinoma (ESCC),
      remain unknown. In the present study, we found that EYA4 was underexpressed and
      hypermethylated in most of the ESCC cell lines tested (85.7%, 6/7). Treatment
      with 5-aza-dC and/or trichostatin A (TSA) restored EYA4 expression in ESCC cell
      lines, which indicates that EYA4 expression was epigenetically regulated.
      Similarly, EYA4 was aberrantly hypermethylated in ESCC tissues (78%, 39/50) and
      downregulation of EYA4 occurred in approximately 65% of primary ESCC at protein
      level where it was associated significantly with TNM stage and lymph node
      metastases. Knockdown of EYA4 in KYSE30 and KYSE70 ESCC cells using small hairpin
      RNA increased migration and invasive motility in vitro. Conversely, the
      overexpression of EYA4 in KYSE180 and KYSE450 promoted an epithelial phenotype,
      which consisted of decreased migration and invasion abilities and a decrease in
      TGF-beta1-induced epithelial-mesenchymal transition. Mechanistically, EYA4
      overexpression reduced the phosphorylation of Akt and glycogen synthase kinase
      (GSK) 3beta, which led to the inactivation of slug. In addition, we found that
      TGF-beta1 decreased EYA4 expression in both a dose-dependent and a time-dependent
      manner in KYSE30 cells, accompanied by an increase in the expression of DNA
      methyltransferases, especially DNMT3A. In summary, EYA4 is frequently
      hypermethylated in ESCC and may function as a tumor suppressor gene in the
      development of ESCC.

PMID- 29660225
TI  - Spotlights on our sister journals: Angew. Chem. Int. Ed. 17/2018.

PMID- 29660224
TI  - Shortened therapy of eight weeks with paritaprevir/ritonavir/ombitasvir and
      dasabuvir is highly effective in people with recent HCV genotype 1 infection.
AB  - Paritaprevir/ritonavir/ombitasvir and dasabuvir with or without ribavirin for 12
      weeks are approved for treatment of chronic HCV genotype 1 infection. This study
      assessed the efficacy of shortened duration paritaprevir/ritonavir/ombitasvir and
      dasabuvir with or without ribavirin for 8 weeks among people with recent HCV
      infection. In this open-label single-arm trial conducted in Australia, England
      and New Zealand, adults with recent HCV (duration of infection <12 months)
      received paritaprevir/ritonavir/ombitasvir and dasabuvir (with weight-based
      ribavirin for genotypes 1a and 1, no subtype) for 8 weeks. The primary endpoint
      was sustained virological response at 12 weeks post-treatment (SVR12) in the
      intention-to-treat (ITT) population. Thirty people (median age 38 years, male
      93%) commenced treatment (with ribavirin, 97%), of whom 77% (n = 23) were HIV
      positive, 93% (n = 28) had genotype 1a infection and 53% (n = 16) had ever
      injected drugs. Median maximum ALT in the preceding 12 months was 433 IU/L (IQR
      321, 1012). Acute clinical hepatitis with ALT > 10 x ULN was documented in 83% (n
      = 25); one participant (3%) had jaundice. At baseline, median estimated duration
      of infection was 30 weeks (range 11, 51), and median HCV RNA was 5.7 log10 IU/mL
      (range 2.7, 7.3). SVR12 was achieved in 97% (29/30; early discontinuation at week
      2, n = 1; per protocol 100%, 29/29). No relapse or reinfection was observed. In
      conclusion, paritaprevir/ritonavir/ombitasvir and dasabuvir (with ribavirin) for
      eight weeks were highly effective among HIV-positive and HIV-negative individuals
      with recent HCV infection. These data support the use of this shortened duration
      direct-acting antiviral regimen in this population.

PMID- 29660226
TI  - Delays in lung cancer management pathways between rural and urban patients in
      North Queensland: a mixed methods study.
AB  - BACKGROUND: Despite advances in medical therapies, disparity in outcome between
      rural and urban patients remain in Australia and many Western countries. AIMS: To
      examine time delays in lung cancer referral pathways in North Queensland (NQ),
      Australia, and explore patients' perspective of factors causing these delays.
      METHODS: Prospective study of patients attending three cancer centres in
      Townsville, Cairns and Mackay in NQ from 2009 to 2012. Times along referral
      pathway were divided as follows: Onset of symptoms to treatment (T1), symptoms to
      general practitioner (GP) (T2), GP to specialist (T3) and Specialist to treatment
      (T4). Quantitative and qualitative methods were used for analysis. RESULTS: In
      total, 252 patients were participated. T1 was influenced by remoteness (125 days
      in Townsville vs 170 days for remote, P = 0.01), T2 by level of education (91
      days for primary education vs 61 days for secondary vs 23 days for
      tertiary/Technical and Further Education (TAFE), P = 0.006), and age group (14
      days for 31-50 years, 61 days for 51-70 years, 45 days for >71 years, P = 0.026),
      T3 by remoteness (15 days for Townville and 29.5 days for remote, P = 0.02) and
      T4 by stage of disease (21 days for Stage I, 11 days for Stage II, 34 days for
      Stage III 18 days for Stage IV, P = 0.041). Competing priorities of family and
      work and cost and inconvenience of travel were perceived as rural barriers.
      CONCLUSION: Remoteness, age and level of education were related to delays in
      various time lines in lung cancer referral pathways in NQ. Provision of
      specialist services closer to home may decrease delays by alleviating burden of
      cost and inconvenience of travel.

PMID- 29660227
TI  - The limited contribution of large trees to annual biomass production in an old
      growth tropical forest.
AB  - Although the importance of large trees regarding biodiversity and carbon stock in
      old-growth forests is undeniable, their annual contribution to biomass production
      and carbon uptake remains poorly studied at the stand level. To clarify the role
      of large trees in biomass production, we used data of tree growth, mortality, and
      recruitment monitored during 20 yr in 10 4-ha plots in a species-rich tropical
      forest (Central African Republic). Using a random block design, three different
      silvicultural treatments, control, logged, and logged + thinned, were applied in
      the 10 plots. Annual biomass gains and losses were analyzed in relation to the
      relative biomass abundance of large trees and by tree size classes using a
      spatial bootstrap procedure. Although large trees had high individual growth
      rates and constituted a substantial amount of biomass, stand-level biomass
      production decreased with the abundance of large trees in all treatments and
      plots. The contribution of large trees to annual stand-level biomass production
      appeared limited in comparison to that of small trees. This pattern did not only
      originate from differences in abundance of small vs. large trees or differences
      in initial biomass stocks among tree size classes, but also from a reduced
      relative growth rate of large trees and a relatively constant mortality rate
      among tree size classes. In a context in which large trees are increasingly
      gaining attention as being a valuable and a key structural characteristic of
      natural forests, the present study brought key insights to better gauge the
      relatively limited role of large trees in annual stand-level biomass production.
      In terms of carbon uptake, these results suggest, as already demonstrated, a low
      net carbon uptake of old-growth forests in comparison to that of logged forests.
      Tropical forests that reach a successional stage with relatively high density of
      large trees progressively cease to be carbon sinks as large trees contribute
      sparsely or even negatively to the carbon uptake at the stand level.

PMID- 29660228
TI  - Selective Hydrogenation of CO2 to Ethanol over Cobalt Catalysts.
AB  - Methods for the hydrogenation of CO2 into valuable chemicals are in great demand
      but their development is still challenging. Herein, we report the selective
      hydrogenation of CO2 into ethanol over non-noble cobalt catalysts (CoAlOx ),
      presenting a significant advance for the conversion of CO2 into ethanol as the
      major product. By adjusting the composition of the catalysts through the use of
      different prereduction temperatures, the efficiency of CO2 to ethanol
      hydrogenation was optimized; the catalyst reduced at 600  degrees  gave an
      ethanol selectivity of 92.1 % at 140  degrees C with an ethanol time yield of
      0.444 mmol g-1  h-1 . Operando FT-IR spectroscopy revealed that the high ethanol
      selectivity over the CoAlOx catalyst might be due to the formation of acetate
      from formate by insertion of *CHx , a key intermediate in the production of
      ethanol by CO2 hydrogenation.

PMID- 29660229
TI  - Extracellular matrix composition modulates PDAC parenchymal and stem cell
      plasticity and behavior through the secretome.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers. Its
      aggressiveness is driven by an intense fibrotic desmoplastic reaction in which
      the increasingly collagen I-rich extracellular matrix (ECM) and several cell
      types, including cancer stem cells (CSCs), create a tumor-supportive environment.
      However, how ECM composition regulates CSC dynamics and their relationship with
      the principle parenchymal tumor population to promote early invasive growth is
      not yet characterized. For this, we utilized a platform of 3D organotypic
      cultures composed of laminin-rich Matrigel, representative of an early tumor,
      plus increasing concentrations of collagen I to simulate malignant stroma
      progression. As ECM collagen I increases, CSCs progress from a rapidly growing,
      vascular phenotype to a slower growing, avascular phase, while maintaining their
      endothelial-like gene signatures. This transition is supported autocrinically by
      the CSCs and paracrinically by the parenchymal cells via their ECM-dependent
      secretomes. Indeed, when growing on an early tumor ECM, the CSCs are dedicated
      toward the preparation of a vascular niche by (a) activating their growth
      program, (b) secreting high levels of proangiogenic factors which stimulate both
      angiogenesis and vasculogenic mimicry, and (c) overexpressing VEGFR-2, which is
      activated by VEGF secreted by both the CSC and parenchymal cells. On Matrigel,
      the more differentiated parenchymal tumor cell population had reduced growth but
      a high invasive capacity. This concerted high local invasion of parenchymal cells
      into the CSC-derived vascular network suggests that a symbiotic relationship
      between the parenchymal cells and the CSCs underlies the initiation and
      maintenance of early PDAC infiltration and metastasis.

PMID- 29660230
TI  - The use of antimicrobials as adjuvant therapy for the treatment of obesity and
      insulin resistance: Effects and associated mechanisms.
AB  - The intestinal microbiota has come to be considered an additional risk factor for
      the development of metabolic diseases. Considering the potential role of
      antimicrobials as modulators of the intestinal microbiota, they have been
      investigated for use in the adjuvant treatment of obesity and insulin resistance
      (IR). In this regard, the present manuscript aimed to review the effect of
      regular use of antimicrobials on the treatment of obesity and/or IR, as well as
      its associated mechanisms. The regular use of antimicrobials does not seem to
      influence the body weight and adiposity of its consumer. Regarding IR, clinical
      trials did not observe positive effects, on the other hand, most of the
      experimental studies observed an increase in insulin sensitivity. The mechanisms
      used by antimicrobials that could lead to the improvement of insulin sensitivity
      are dependent on the modulation of the intestinal microbiota. This modulation
      would lead to a reduction in the stimulation of the immune system, as a
      consequence of improved intestinal barrier and/or the reduction of gram-negative
      bacteria in the microbiota. In addition, the secretion of glucagon-like peptide-1
      would be modulated by metabolites produced by the intestinal microbiota, such as
      secondary bile acids and short-chain fatty acids. Based on the results obtained
      to date, more studies should be performed to elucidate the effect of these drugs
      on obesity and IR, as well as the mechanisms involved. In addition, the cost
      benefit of the regular use of antimicrobials should be investigated, as this
      practice may lead to the development of antimicrobial-resistant microorganisms.

PMID- 29660232
TI  - Highly efficient high-performance liquid chromatographic separation of xylene
      isomers and phthalate acid esters on a homemade DUT-67(Zr) packed column.
AB  - In this study, the baseline separations of xylene isomers and phthalate acid
      esters on a homemade DUT-67(Zr) packed column were achieved, respectively. The
      high selectivity for xylene isomers and phthalate acid esters was obtained with
      the increase in temperature and decrease in the retention time. The
      hydrophobicity of xylene isomers and phthalate acid esters resulted in the
      different separation time on the DUT-67(Zr) packed column. The relative standard
      deviation values of retention time, peak area, peak height, and half peak width
      for five repeat separation of the xylene isomers were 0.26-0.35, 2.11-2.26, 1.51
      2.03, and 0.29-0.77%, and the values of the phthalate acid esters on DUT-67(Zr)
      column were 0.1-0.4, 4.4-5.2, 3.9-6.3, and 0.6-2.1%, respectively. The
      thermodynamic properties indicated that the separation of xylene isomers was
      controlled by DeltaH and DeltaS, but the separation of phthalate acid esters was
      mainly controlled by DeltaS.

PMID- 29660233
TI  - Nonalcoholic fatty liver disease is associated with decreased lung function.
AB  - BACKGROUND & AIMS: The association between nonalcoholic fatty liver disease and
      lung function has not been fully examined. The aim of this study was to clarify
      the association between nonalcoholic fatty liver disease and lung function in
      general population by performing cross-sectional and longitudinal analysis.
      METHODS: Participants without hepatic and respiratory disease who underwent
      regular health exams including hepatic sonography and spirometry with at least 3
      years' follow-up were included. In cross-sectional analysis, the association
      between nonalcoholic fatty liver disease and lung function at baseline was
      examined with multiple regression models. The longitudinal analysis was performed
      by mixed linear regression models with propensity score matching. RESULTS: Of 11
      892 eligible participants (mean age, 47.7 years; male, 47.2%), 3815(32.1%) had
      nonalcoholic fatty liver disease based on sonography. In cross-sectional
      analysis, the nonalcoholic fatty liver disease group had lower adjusted forced
      expiratory volume in 1-second (men, 3.52 vs 3.44 L, P < .001; women, 2.62 vs 2.45
      L, P < .001) and forced vital capacity (men, 4.33 vs 4.24 L, P < .001; women,
      3.11 vs 2.97 L, P < .001) than the control group. In longitudinal analysis,
      during the mean follow-up period of 6.6 years, there were no significant
      differences in forced expiratory volume in 1-second or forced vital capacity
      decline rates between two groups in the propensity score-matched cohorts (n =
      4558). However, those with high nonalcoholic fatty liver disease fibrosis score
      and fibrosis-4 (men, -21.7 vs -27.4 mL/y, P = .001; women, -22.4 vs -27.9 mL/y, P
      = .016) showed significantly faster decline in forced vital capacity compared to
      those with low scores. CONCLUSIONS: Nonalcoholic fatty liver disease was
      associated with decreased lung function at baseline but was not associated with
      accelerated lung function decline in the propensity score-matched cohort.
      However, hepatic fibrosis was significantly associated with rapid forced vital
      capacity decline.

PMID- 29660231
TI  - Plakoglobin restores tumor suppressor activity of p53R175H mutant by sequestering
      the oncogenic potential of beta-catenin.
AB  - Tumor suppressor/transcription factor p53 is mutated in over 50% of all cancers.
      Some mutant p53 proteins have not only lost tumor suppressor activities but they
      also gain oncogenic functions (GOF). One of the most frequently expressed GOF p53
      mutants is Arg175His (p53R175H ) with well-documented roles in cancer development
      and progression. Plakoglobin is a cell adhesion and signaling protein and a
      paralog of beta-catenin. Unlike beta-catenin that has oncogenic function through
      its role in the Wnt pathway, plakoglobin generally acts as a tumor/metastasis
      suppressor. We have shown that plakoglobin interacted with wild type and a number
      of p53 mutants in various carcinoma cell lines. Plakoglobin and mutant p53
      interacted with the promoter and regulated the expression of several p53 target
      genes. Furthermore, plakoglobin interactions with p53 mutants restored their
      tumor suppressor/metastasis activities in vitro. GOF p53 mutants induce
      accumulation and oncogenic activation of beta-catenin. Previously, we showed that
      one mechanism by which plakoglobin may suppress tumorigenesis is by sequestering
      beta-catenin's oncogenic activity. Here, we examined the effects of p53R175H
      expression on beta-catenin accumulation and transcriptional activation and their
      modifications by plakoglobin coexpression. We showed that p53R175H expression in
      plakoglobin null cells increased total and nuclear levels of beta-catenin and its
      transcriptional activity. Coexpression of plakoglobin in these cells promoted
      beta-catenin's proteasomal degradation, and decreased its nuclear levels and
      transactivation. Wnt/beta-catenin targets, c-MYC and S100A4 were upregulated in
      p53R175H cells and were downregulated when plakoglobin was coexpressed.
      Plakoglobin-p53R175H cells also showed significant reduction in their migration
      and invasion in vitro.

PMID- 29660234
TI  - Evaluation of chronic kidney disease in cancer patients: is there a preferred
      estimation formula?
AB  - BACKGROUND: The evaluation of chronic kidney disease (CKD) in cancer patients
      seems to rely mostly on the Cockcroft-Gault (CG) formula or the creatinine levels
      to adjust treatment dosages which is a practice refuted by internists. AIMS: We
      evaluate the overall agreement of the CG, modification of diet in renal disease
      (MDRD) and CKD-epidemiology collaboration equations (CKD-EPI) equation with the
      newly devised Janowitz and Williams' (JW) equation. METHODS: The renal function
      was estimated in 235 cancer patients according to the CG, MDRD, body surface area
      (BSA)-adjusted MDRD, CKD-EPI, BSA-adjusted CKD-EPI and JW formulae. RESULTS: JW
      equation was more in agreement with CG and CKD-EPI estimations than the other
      equations. Taking JW equation as reference, receiver operating characteristic
      curve analysis showed that CG eGFR had the higher area under the curve when
      compared with other equations. Hierarchical cluster analysis showed more
      proximity between CG and JW equations than the other equations. CONCLUSION: The
      newly proposed JW eGFR estimation was more in agreement with CG equation than the
      other equations.

PMID- 29660235
TI  - Inhibition of OsSWEET11 function in mesophyll cells improves resistance of rice
      to sheath blight disease.
AB  - Pathogen-host interaction is a complicated process; pathogens mainly infect host
      plants to acquire nutrients, especially sugars. Rhizoctonia solani, the causative
      agent of sheath blight disease, is a major pathogen of rice. However, it is not
      known how this pathogen obtains sugar from rice plants. In this study, we found
      that the rice sugar transporter OsSWEET11 is involved in the pathogenesis of
      sheath blight disease. Quantitative real-time polymerase chain reaction (qRT-PCR)
      and beta-d-glucuronidase expression analyses showed that R. solani infection
      significantly enhanced OsSWEET11 expression in leaves amongst the clade III SWEET
      members. The analyses of transgenic plants revealed that Ossweet11 mutants were
      less susceptible, whereas plants overexpressing OsSWEET11 were more susceptible,
      to sheath blight compared with wild-type controls, but the yield of OsSWEET11
      mutants and overexpressors was reduced. SWEETs become active on oligomerization.
      Split-ubiquitin yeast two-hybrid, bimolecular fluorescence complementation and co
      immunoprecipitation assays showed that mutated OsSWEET11 interacted with normal
      OsSWEET11. In addition, expression of conserved residue mutated AtSWEET1
      inhibited normal AtSWEET1 activity. To analyse whether inhibition of OsSWEET11
      function in mesophyll cells is related to defence against this disease, mutated
      OsSWEET11 was expressed under the control of the Rubisco promoter, which is
      specific for green tissues. The resistance of transgenic plants to sheath blight
      disease, but not other disease, was improved, whereas yield production was not
      obviously affected. Overall, these results suggest that R. solani might acquire
      sugar from rice leaves by the activation of OsSWEET11 expression. The plants can
      be protected from infection by manipulation of the expression of OsSWEET11
      without affecting the crop yield.

PMID- 29660236
TI  - Oxylipins from both pathogen and host antagonize jasmonic acid-mediated defence
      via the 9-lipoxygenase pathway in Fusarium verticillioides infection of maize.
AB  - Oxylipins are a newly emerging group of signals that serve defence roles or
      promote virulence. To identify specific host and fungal genes and oxylipins
      governing the interactions between maize and Fusarium verticillioides, maize wild
      type and lipoxygenase3 (lox3) mutant were inoculated with either F.
      verticillioides wild-type or linoleate-diol-synthase 1-deleted mutant
      (DeltaFvlds1D). The results showed that lox3 mutants were more resistant to F.
      verticillioides. The reduced colonization on lox3 was associated with reduced
      fumonisin production and with a stronger and earlier induction of ZmLOX4, ZmLOX5
      and ZmLOX12. In addition to the reported defence function of ZmLOX12, we showed
      that lox4 and lox5 mutants were more susceptible to F. verticillioides and
      possessed decreased jasmonate levels during infection, suggesting that these
      genes are essential for jasmonic acid (JA)-mediated defence. Oxylipin profiling
      revealed a dramatic reduction in fungal linoleate diol synthase 1 (LDS1)-derived
      oxylipins, especially 8-HpODE (8-hydroperoxyoctadecenoic acid), in infected lox3
      kernels, indicating the importance of this molecule in virulence. Collectively,
      we make the following conclusions: (1) LOX3 is a major susceptibility factor
      induced by fungal LDS1-derived oxylipins to suppress JA-stimulating 9-LOXs; (2)
      LOX3-mediated signalling promotes the biosynthesis of virulence-promoting
      oxylipins in the fungus; and (3) both fungal LDS1- and host LOX3-produced
      oxylipins are essential for the normal infection and colonization processes of
      maize seed by F. verticillioides.

PMID- 29660237
TI  - Multiplexed Isobaric Tag-Based Profiling of Seven Murine Tissues Following In
      Vivo Nicotine Treatment Using a Minimalistic Proteomics Strategy.
AB  - Nicotine is a major addictive compound in tobacco and a component of smoking
      related products, such as e-cigarettes. Once internalized, nicotine can perturb
      many cellular pathways and can induce alterations in proteins across different
      cell types; however, the mechanisms thereof remain undetermined. The authors
      hypothesize that both tissue-specific and global protein abundance alterations
      result from nicotine exposure. Presented here is the first proteomic profiling of
      multiple tissues from mice treated orally with nicotine. Proteins extracted from
      seven tissues (brain, heart, kidney, liver, lung, pancreas, and spleen) from
      treated (n = 5) and untreated control (n = 5) mice are assembled into a TMT10
      plex experiment. A minimalistic proteomics strategy is employed using TMT
      reagents efficiently and centrifugation-based reversed-phase columns to
      streamline sample preparation. Combined, over 11 000 non-redundant proteins from
      over 138 000 different peptides are quantified in seven TMT10-plex experiments.
      Between 7 and 126 proteins are significantly altered in tissues from nicotine
      exposed mice, 11 which are altered in two or more tissues. Our data showcase the
      vast extent of nicotine exposure across murine tissue.

PMID- 29660238
TI  - Heat shock transcription factor 3 regulates plant immune response through
      modulation of salicylic acid accumulation and signalling in cassava.
AB  - As the terminal components of signal transduction, heat stress transcription
      factors (Hsfs) mediate the activation of multiple genes responsive to various
      stresses. However, the information and functional analysis are very limited in
      non-model plants, especially in cassava (Manihot esculenta), one of the most
      important crops in tropical areas. In this study, 32 MeHsfs were identified from
      the cassava genome; the evolutionary tree, gene structures and motifs were also
      analysed. Gene expression analysis found that MeHsfs were commonly regulated by
      Xanthomonas axonopodis pv. manihotis (Xam). Amongst these MeHsfs, MeHsf3 was
      specifically located in the cell nucleus and showed transcriptionally activated
      activity on heat stress elements (HSEs). Through transient expression in
      Nicotiana benthamiana leaves and virus-induced gene silencing (VIGS) in cassava,
      we identified the essential role of MeHsf3 in plant disease resistance, by
      regulating the transcripts of Enhanced Disease Susceptibility 1 (EDS1) and
      pathogen-related gene 4 (PR4). Notably, as regulators of defence susceptibility,
      MeEDS1 and MePR4 were identified as direct targets of MeHsf3. Moreover, the
      disease sensitivity of MeHsf3- and MeEDS1-silenced plants could be restored by
      exogenous salicylic acid (SA) treatment. Taken together, this study highlights
      the involvement of MeHsf3 in defence resistance through the transcriptional
      activation of MeEDS1 and MePR4.

PMID- 29660239
TI  - The population genetic test Tajima's D identifies genes encoding pathogen
      associated molecular patterns and other virulence-related genes in Ralstonia
      solanacearum.
AB  - The detection of pathogen-associated molecular patterns (PAMPs) by plant pattern
      recognition receptors (PRRs) is an essential part of plant immunity. Until
      recently, elf18, an epitope of elongation factor-Tu (EF-Tu), was the sole
      confirmed PAMP of Ralstonia solanacearum, the causal agent of bacterial wilt
      disease, limiting our understanding of R. solanacearum-plant interactions.
      Therefore, we set out to identify additional R. solanacearum PAMPs based on the
      hypothesis that genes encoding PAMPs are under selection to avoid recognition by
      plant PRRs. We calculated Tajima's D, a population genetic test statistic which
      identifies genes that do not evolve neutrally, for 3003 genes conserved in 37 R.
      solanacearum genomes. The screen flagged 49 non-neutrally evolving genes,
      including not only EF-Tu but also the gene for Cold Shock Protein C, which
      encodes the PAMP csp22. Importantly, an R. solanacearum allele of this PAMP was
      recently identified in a parallel independent study. Genes coding for efflux
      pumps, some with known roles in virulence, were also flagged by Tajima's D. We
      conclude that Tajima's D is a straightforward test to identify genes encoding
      PAMPs and other virulence-related genes in plant pathogen genomes.

PMID- 29660241
TI  - COPD is independently associated with 6-month survival in patients who have life
      support withheld in intensive care.
AB  - BACKGROUND: In-hospital outcomes following decisions of withholding or
      withdrawing in Intensive Care Unit (ICU) patients have been previously assessed,
      little is known about outcomes after ICU and hospital discharge. Our objective
      was to report the 6-month outcomes of discharged patients who had treatment
      limitations in a general ICU and to identify prognostic factors of survival.
      METHODS: We retrospectively collected the data of patients discharged from the
      ICU for whom life support was withheld from 2009 to 2011. We assessed the
      survival status of all patients at 6 months post-discharge and their duration of
      survival. Survivors and non-survivors were compared using univariate and
      multivariate analyses by Cox's proportional hazard model. RESULTS: One hundred
      fourteen patients were included. The survival rate at 6 months was 58.8%.
      Survival was associated with acute respiratory failure (48% vs 19%, P = .006), a
      history of COPD (40% vs 21%, P = .03) and a lower SAPS II score (44 vs 49, P =
      .006). We identified a history of COPD as a prognostic factor for survival in the
      multivariate analysis (HR = 2.1; IC 95% 1.02-4.36, P = .04). CONCLUSION: A total
      of 58.8% of patients for whom life-sustaining therapies were withheld in the ICU
      survived for at least 6 months after discharge. Patients with COPD appeared to
      have a significantly higher survival rate. The decision to withhold life support
      in patients should not lead to a cessation of post-ICU care and to non
      readmission of COPD patients.

PMID- 29660240
TI  - Reactive oxygen species signaling and stomatal movement in plant responses to
      drought stress and pathogen attack.
AB  - Stomata, the pores formed by a pair of guard cells, are the main gateways for
      water transpiration and photosynthetic CO2 exchange, as well as pathogen invasion
      in land plants. Guard cell movement is regulated by a combination of
      environmental factors, including water status, light, CO2 levels and pathogen
      attack, as well as endogenous signals, such as abscisic acid and apoplastic
      reactive oxygen species (ROS). Under abiotic and biotic stress conditions,
      extracellular ROS are mainly produced by plasma membrane-localized NADPH
      oxidases, whereas intracellular ROS are produced in multiple organelles. These
      ROS form a sophisticated cellular signaling network, with the accumulation of
      apoplastic ROS an early hallmark of stomatal movement. Here, we review recent
      progress in understanding the molecular mechanisms of the ROS signaling network,
      primarily during drought stress and pathogen attack. We summarize the roles of
      apoplastic ROS in regulating stomatal movement, ABA and CO2 signaling, and
      immunity responses. Finally, we discuss ROS accumulation and communication
      between organelles and cells. This information provides a conceptual framework
      for understanding how ROS signaling is integrated with various signaling pathways
      during plant responses to abiotic and biotic stress stimuli.

PMID- 29660242
TI  - Iridoids from Pedicularis verticillata and Their Anti-Complementary Activity.
AB  - Three new iridoids named as pediverticilatasin A - C (1 - 3, resp.), together
      with five known iridoids (4 - 8, resp.) were isolated from the whole plants of
      Pedicularis verticillata. The structures of three new compounds were identified
      as (1S,7R)-1-ethoxy-1,5,6,7-tetrahydro-7-hydroxy-7-methylcyclopenta[c]pyran-4(3H)
      one (1), (1S,4aS,7R,7aS)-1-ethoxy-1,4a,5,6,7,7a-hexahydro-7-hydroxy-7
      methylcyclopenta[c]pyran-4-carboxylic acid (2), (1S,4aS,7R,7aS)-1-ethoxy
      1,4a,5,6,7,7a-hexahydro-7-hydroxy-7-methylcyclopenta[c]pyran-4-carbaldehyde (3).
      Their structures were elucidated on the basis of spectroscopic methods and
      compared with the NMR spectra data in the literature. All compounds were
      evaluated for their anti-complementary activity on the classical pathway of the
      complement system in vitro. Among which, compounds 1, 3, and 6 exhibited anti
      complementary effects with CH50 values ranging from 0.43 to 1.72 mm, which are
      plausible candidates for developing potent anti-complementary agents.

PMID- 29660243
TI  - Autophagy-A key pathway for cardiac health and longevity.
AB  - As average life expectancy continues to rise in the developed world, age
      associated pathologies are increasing in prevalence. The hallmarks of cardiac
      ageing include cardiomyocyte loss, fibrosis and hypertrophy, all of which
      contribute to an increased incidence of cardiac disease. At the molecular level,
      cellular ageing is characterized by increased ROS production, mitochondrial
      dysfunction and the accumulation of damaged proteins and organelles.
      Cardiomyocytes and other senescent cell types rely upon autophagy, a lysosome
      mediated degradation pathway, to remove potentially toxic protein aggregates and
      damaged organelles from the cellular milieu. However, increasing lines of
      evidence point to an age-associated decrease in cardiomyocyte autophagy, with
      predictably negative consequences for cardiac function and health. Conversely,
      stimulation of autophagy has been shown to improve cellular health and cardiac
      function and to increase lifespan in numerous model organisms. Clearly, autophagy
      represents a critical pathway for cellular vitality, as well as a promising
      therapeutic target for the treatment of age-related cardiac pathologies. In this
      review, we will discuss the mechanism of autophagy and its regulation in the
      cell, the role of autophagy in the ageing heart, and how the autophagy pathway
      might be targeted to improve cardiac health.

PMID- 29660244
TI  - Unaccounted for regression to the mean renders conclusion of article titled "Uric
      acid lowering in relation to HbA1c reductions with the SGLT2 inhibitor
      tofogliflozin" unsubstantiated.

PMID- 29660245
TI  - 1,2,3-Triazole Tagged 3H-Pyrano[2,3-d]pyrimidine-6-carboxylate Derivatives:
      Synthesis, in Vitro Cytotoxicity, Molecular Docking and DNA Interaction Studies.
AB  - A series of novel ethyl 2,7-dimethyl-4-oxo-3-[(1-phenyl-1H-1,2,3-triazol-4
      yl)methyl]-4,5-dihydro-3H-pyrano[2,3-d]pyrimidine-6-carboxylate derivatives 7a -
      7m were efficiently synthesized employing click chemistry approach and evaluated
      for in vitro cytotoxic activity against four tumor cell lines: A549 (human lung
      adenocarcinoma cell line), HepG2 (human hematoma), MCF-7 (human breast
      adenocarcinoma), and SKOV3 (human ovarian carcinoma cell line). Among the
      compounds tested, the compounds 7a, 7b, 7f, 7l, and 7m have shown potential and
      selective activity against human lung adenocarcinoma cell line (A549) with IC50
      ranging from 0.69 to 6.74 MUm. Molecular docking studies revealed that the
      compounds 7a, 7b, 7f, 7l, and 7m are potent inhibitors of human DNA topoisomerase
      II and also showed compliance with stranded parameters of drug likeness. The
      calculated binding constants, kb , from UV/VIS absorptional binding studies of 7a
      and 7l with CT-DNA were 10.77 * 104 , 6.48 * 104 , respectively. Viscosity
      measurements revealed that the binding could be surface binding mainly due to
      groove binding. DNA cleavage study showed that 7a and 7l have the potential to
      cleave pBR322 plasmid DNA without any external agents.

PMID- 29660246
TI  - Cyclic band compression in toroidal capillary electrophoresis delivers an
      unlimited number of theoretical plates with a quadratic growth in time and a
      constant peak capacity.
AB  - Analytical instruments able to provide extremely high sensitivities, separation
      efficiencies, and peak capacities are important for both applied sciences and
      basic research. It is even more interesting if this can be achieved within
      organic, aqueous, and physiological solutions without restricting the operation
      parameters, such as buffer pH, temperature, ionic strength, and background
      electrolyte composition. Toroidal capillary electrophoresis offers this
      potential, as was recently proposed and demonstrated. In this platform, the
      analytes perform continuous round trips inside a fused-silica capillary having a
      torus-like shape. In the present work, the equations of the number of plates and
      peak capacity are deduced when on-column cyclic thermal band compression is
      applied. They are expressed as a function of the number of turns performed by the
      analyte, axial length of the toroid, number of microholes (reservoirs),
      compression factor, number of compression events performed per turn, and applied
      voltage. It was found that the variances of the bands reach a steady state,
      regardless of the number of dispersion mechanisms present. Consequently, the
      number of theoretical plates grows indefinitely as the square of time. The
      expression of peak capacity shows a well-defined limiting value that remains
      constant over time.

PMID- 29660247
TI  - Pulmonary functions in pseudoexfoliation syndrome.
AB  - OBJECTIVES: It is well-known that pseudoexfoliative material deteriorates iris
      dilatation function. This material was also found in lung tissue. The aim of the
      study was to evaluate pulmonary function in patients with pseudoexfoliation.
      METHODS: This prospective study included 60 pseudoexfoliation syndrome patients
      without any pulmonary diseases and 52 age- and gender-matched controls without
      any pulmonary diseases. Patients were asked about their cigarette use and the
      presence of any systemic diseases such as diabetes mellitus, arterial
      hypertension and asthma. All cases underwent full ophthalmologic and general
      medical examinations including pulmonary auscultation and pulmonary posterior
      anterior X-ray. Pulmonary function tests were used for evaluation of pulmonary
      function. FVC, FEV1 , FEV1 %, FEV1 /FVC and saturation values were recorded.
      RESULTS: Mean age was 67.1 +/- 8.8 (44-82) years in the pseudoexfoliation group
      and 63.8 +/- 9.4 (43-82) years in the control group (P > .05). Mean FEV1 was 1.60
      +/- 0.62 in the pseudoexfoliation group and 1.84 +/- 0.61 in the control group (P
      = .036). Mean FEV1 % was 70.65 +/- 23.89 in the pseudoexfoliation group and 83.46
      +/- 17.83 in the control group (P = .002). Mean FEV1 /FVC ratios were 0.72 +/-
      0.15 in the pseudoexfoliation group and 0.77 +/- 0.11 in the control group (P =
      .043). No statistically significant differences were found between the groups for
      FVC, saturation or cigarette use. CONCLUSION: These results suggest that there is
      decline in some pulmonary functions in pseudoexfoliation syndrome.

PMID- 29660248
TI  - Exploring the Performance Improvement of the Oxygen Evolution Reaction in a
      Stable Bimetal-Organic Framework System.
AB  - Despite wide applications of bimetallic electrocatalysis in oxygen evolution
      reaction (OER) owing to their superior performance, the origin of the improved
      performance remains elusive. The underlying mechanism was explored by designing
      and synthesizing a series of stable metal-organic frameworks (MOFs: NNU-21-24)
      based on trinuclear metal carboxylate clusters and tridentate carboxylate
      ligands. Among the examined stable MOFs, NNU-23 exhibits the best OER
      performance; particularly, compared with monometallic MOFs, all the bimetallic
      MOFs display improved OER activity. DFT calculations and experimental results
      demonstrate that introduction of the second metal atom can improve the activity
      of the original atom. The proposed model of bimetallic electrocatalysts affecting
      their OER performance can facilitate design of efficient bimetallic catalysts for
      energy storage and conversion, and investigation of the related catalytic
      mechanisms.

PMID- 29660249
TI  - Shorter hepatitis B immunoglobulin administration is not associated to hepatitis
      B virus recurrence when receiving combined prophylaxis after liver
      transplantation.
AB  - BACKGROUND & AIMS: The combination of hepatitis B immunoglobulin and a
      nucleos(t)ide analogues has markedly reduced the rate of hepatitis B virus
      recurrence after liver transplantation; however, the optimal duration of
      hepatitis B immunoglobulin has not been clarified. This lack of consensus
      perpetuates the use of different strategies. The aim of this study was to
      evaluate the risk factors associated to hepatitis B virus recurrence after liver
      transplantation in a large cohort of patients under different hepatitis B
      immunoglobulin regimens. METHODS: Retrospective multicentre analysis of hepatitis
      B virus-related liver transplantation recipients receiving combined prophylaxis
      (hepatitis B immunoglobulin + nucleos(t)ide analogues). The strategy of short
      term hepatitis B immunoglobulin was compared to lifelong administration.
      Hepatitis B virus recurrence was defined as positive HBsAg after liver
      transplantation. RESULTS: Three hundred and thirty-eight patients were analysed.
      After a median follow-up period of 72 months, 37 patients (11%) developed
      hepatitis B virus recurrence. Hepatocellular carcinoma recurrence and lamivudine
      resistance after liver transplantation were the only factors independently
      associated to hepatitis B virus recurrence (HR 5.4 [2.3-12] and 9.3 [4.2-20]
      respectively P < .001). HBsAg reappearance after hepatitis B virus recurrence was
      transient (16 patients), persistent (15) or alternant (6). The hepatitis B
      immunoglobulin regimen did not have an impact on the rate or evolution of
      hepatitis B virus recurrence. Overall, patient survival was good and not
      influenced by hepatitis B virus recurrence (82% at 5 years). Fulminant liver
      failure, hepatitis C coinfection or hepatocellular carcinoma at liver
      transplantation were independent risk factors for lower survival. CONCLUSIONS:
      Liver transplantation is an effective treatment for hepatitis B virus-related
      liver disease. Since the introduction of combined prophylaxis the rate of
      hepatitis B virus recurrence is very low. However, lifelong hepatitis B
      immunoglobulin administration does not seem necessary to reduce hepatitis B virus
      recurrence.

PMID- 29660250
TI  - A sensitive, high-throughput, and ecofriendly method for the determination of
      lumefantrine, artemether, and its active metabolite dihydroartemisinin by
      supercritical fluid chromatography and tandem mass spectrometry.
AB  - A quick and sensitive supercritical fluid chromatography with tandem mass
      spectrometry method for the simultaneous determination of lumefantrine,
      artemether, and its active metabolite dihydroartemisinin in rat plasma was
      developed and validated. The chromatographic separation was performed on an
      ACQUITY UPC2 TM BEH 2-EP column within 2.5 min by gradient elution using
      compressed CO2 and methanol containing 2 mM ammonium acetate as the mobile
      phases. Detection was achieved by multiple reaction monitoring using electrospray
      ionization in the positive ionization mode. For sample preparation, 50 MUL of the
      sample was processed by modified high-throughput, one-step protein precipitation
      using hydrogen peroxide as a stabilizer to protect the endoperoxide-containing
      artemisinin derivatives from degradation. The calibration curves were linear over
      the concentration range of 2.0-1000 ng/mL for both artemether and
      dihydroartemisinin, and 1.0-5000 ng/mL for lumefantrine. The values of
      selectivity, lower limit of quantification, linearity, accuracy, precision,
      matrix effects, stability, and recovery met the acceptable range according to the
      Food and Drug Administration guidelines. The developed method enables high
      resolution and speed as well as low cost, low solvent consumption, and short time
      and was successfully applied to pharmacokinetic studies through the intravenous
      administration of an artemether-lumefantrine lipid emulsion in rats.

PMID- 29660251
TI  - The association of nasal patency with small airway resistance in children with
      allergic and nonallergic rhinitis.
AB  - INTRODUCTION: Allergic rhinitis (AR) is immunologically and morphologically
      related to disorders in the lower airway. We investigated the relationship
      between the anatomy of the intranasal cavity and small airway resistance in
      subjects with nonallergic rhinitis (NAR). METHODS: We enrolled 226 children who
      were 7 years old and participated in the Seongnam Atopy Project 2016. We
      evaluated nasal patency using acoustic rhinometry to measure the volume of the
      nasal cavity at 0-5 cm, and measured lung function of the lower airway using an
      impulse oscillometry system (IOS) and spirometry. We also performed skin prick
      tests for 18 aero-allergens, and measured blood total eosinophil counts (TEC) and
      rhinitis symptom scores for the previous month using a visual analog scale (VAS,
      range: 0-10). RESULTS: We examined 226 children, 71 (31.7%) with AR, and 62
      (27.7%) with NAR. Nasal patency in children with AR (median: 8.28 mm3 , IQR: 7.07
      9.83) was lower than that of healthy children (median: 9.3 mm3 , IQR: 7.69-10.64,
      P = 0.011). Multivariate regression analysis showed that nasal patency was
      inversely associated with IOS resistance at 5 Hz after adjustment for compounding
      factors (B = -0.005, SE = 0.0032, P = 0.041). Analysis of NAR subjects, according
      to quartiles of nasal patency and quartiles of small airway resistance (Rrs5),
      indicated that nasal patency decreased as Rrs5 increased (linear trend: P =
      0.020). CONCLUSION: Nasal symptoms and TEC negatively correlated with nasal
      patency. Children with AR and NAR who had poor nasal patency had increased small
      airway resistance.

PMID- 29660252
TI  - Encapsulated oligodendrocyte precursor cell fate is dependent on PDGF-AA release
      kinetics in a 3D microparticle-hydrogel drug delivery system.
AB  - Biomaterial drug delivery systems (DDS) can be used to regulate growth factor
      release and combat the limited intrinsic regeneration capabilities of central
      nervous system (CNS) tissue following injury and disease. Of particular interest
      are systems that aid in oligodendrocyte regeneration, as oligodendrocytes
      generate myelin which surrounds neuronal axons and helps transmit signals
      throughout the CNS. Oligodendrocyte precursor cells (OPCs) are found in small
      numbers in the adult CNS, but are unable to effectively differentiate following
      CNS injury. Delivery of signaling molecules can initiate a favorable OPC
      response, such as proliferation or differentiation. Here, we investigate the
      delivery of one such molecule, platelet derived growth factor-AA (PDGF-AA), from
      poly(lactic-co-glycolic) acid microparticles to OPCs in a 3D polyethylene glycol
      based hydrogel. The goal of this DDS was to better understand the relationship
      between PDGF-AA release kinetics and OPC fate. The system approximates native
      brain tissue stiffness, while incorporating PDGF-AA under seven different
      delivery scenarios. Within this DDS, supply of PDGF-AA followed by PDGF-AA
      withdrawal caused OPCs to upregulate gene expression of myelin basic protein
      (MBP) by factors of 1.6-9.2, whereas continuous supply of PDGF-AA caused OPCs to
      remain proliferative. At the protein expression level, we observed an
      upregulation in O1, a marker for mature oligodendrocytes. Together, these results
      show that burst release followed by withdrawal of PDGF-AA from a hydrogel DDS
      stimulates survival, proliferation, and differentiation of OPCs in vitro. Our
      results could inform the development of improved neural regeneration strategies
      that incorporate delivery of PDGF-AA to the injured CNS. (c) 2018 Wiley
      Periodicals, Inc. J Biomed Mater Res Part A: 106A:2402-2411, 2018.

PMID- 29660253
TI  - Airway stenting for patients with airway stenosis because of small cell lung
      cancer.
AB  - BACKGROUND: Airway stenting has been reported to be useful for patients with
      malignant airway stenosis as a bridge to tumour-specific therapy, such as
      chemotherapy and radiation therapy, as well as palliative therapy. However, its
      role in patients with small-cell lung cancer (SCLC), the most aggressive lung
      cancer subtype, is unclear. We investigated the efficacy of airway stenting for
      patients with airway stenosis resulting from SCLC. METHODS: All stenting
      procedures were performed using both rigid and flexible bronchoscopes under
      general anaesthesia. Among 512 patients who underwent rigid bronchoscopy during a
      9-year period at a single centre, those who underwent airway stenting for airway
      stenosis because of SCLC were retrospectively reviewed. RESULTS: Twenty-one SCLC
      patients with airway stenosis who underwent stenting were eligible for analysis.
      Twelve patients (57%) were chemoradiotherapy-naive. Supplemental oxygen was
      reduced after the procedure in 11 out of 12 patients (92%) who had previously
      required it. Fourteen patients (67%) received tumour-specific therapy after the
      procedure. The median post-procedural survival was 47 days (range, 5-617 days).
      Longer survival was associated with the performance of post-procedural tumour
      specific therapy, low serum lactate dehydrogenase levels and either tracheal or
      bronchial stenosis. CONCLUSIONS: SCLC patients with airway stenting experienced
      longer survival when post-procedural tumour-specific therapy was performed, when
      they showed low serum lactate dehydrogenase levels, and when they had either
      tracheal or bronchial stenosis.

PMID- 29660254
TI  - Phosphatidic acid plays key roles regulating plant development and stress
      responses.
AB  - Phospholipids, including phosphatidic acid (PA), phosphatidylcholine (PC),
      phosphatidylethanolamine (PE), phosphatidylglycerol (PG), phosphatidylserine (PS)
      and phosphoinositides, have emerged as an important class of cellular messenger
      molecules in various cellular and physiological processes, of which PA attracts
      much attention of researchers. In addition to its effect on stimulating vesicle
      trafficking, many studies have demonstrated that PA plays a crucial role in
      various signaling pathways by binding target proteins and regulating their
      activity and subcellular localization. Here, we summarize the functional
      mechanisms and target proteins underlying PA-mediated regulation of cellular
      signaling, development, hormonal responses, and stress responses in plants.

PMID- 29660256
TI  - Quantitative evaluation of optical coherence tomography angiography images of
      diabetic retinopathy eyes before and after removal of projection artifacts.
AB  - Projection artifacts (PAs) affect the quantification of vascular parameters in
      the deep layer optical coherence tomography (OCT) angiography image. This study
      eliminated PA and quantified its effect on imaging. 53 eyes (30 subjects) of
      normal Indian subjects and 113 eyes (92 patients) of type 2 diabetes mellitus
      with retinopathy (DR) underwent imaging with a scan area of 3 mm * 3 mm. In this
      study, a normalized cross-correlation between superficial and deep layer was used
      to remove PA in deep layer. Local fractal analysis was done to compute vascular
      parameters such as foveal avascular zone area (mm2 ), vessel density (%), spacing
      between large vessels (%) and spacing between small vessels (%). Before PA
      removal, vessel density for mild nonproliferative (NPDR), moderate NPDR, severe
      NPDR and proliferative DR were 42.56 +/-1.69%, 40.69 +/-0.72%, 37.34 +/-0.85% and
      35.61 +/-1.26%, respectively. After artifact removal, vessel density was 28.9 +/
      1.22%, 29.9 +/-0.56%, 26.19 +/-0.59% and 24.02 +/-0.94%, respectively. All the
      vascular parameters were statistically significant (P <.001) between normal and
      disease eyes, irrespective of superficial and deep retinal layers. Parafoveal
      sectoral analyses showed that temporal zone had the lowest vessel density and may
      undergo DR-related changes first. The current approach enabled rapid and accurate
      quantitative interpretation of DR eyes, without PA.

PMID- 29660255
TI  - Trans-life cycle acclimation to experimental ocean acidification affects gastric
      pH homeostasis and larval recruitment in the sea star Asterias rubens.
AB  - AIM: Experimental simulation of near-future ocean acidification (OA) has been
      demonstrated to affect growth and development of echinoderm larval stages through
      energy allocation towards ion and pH compensatory processes. To date, it remains
      largely unknown how major pH regulatory systems and their energetics are affected
      by trans-generational exposure to near-future acidification levels. METHODS:
      Here, we used the common sea star Asterias rubens in a reciprocal transplant
      experiment comprising different combinations of OA scenarios, to study trans
      generational plasticity using morphological and physiological endpoints. RESULTS:
      Acclimation of adults to pHT 7.2 (pCO2 3500 MUatm) led to reductions in feeding
      rates, gonad weight and fecundity. No effects were evident at moderate
      acidification levels (pHT 7.4; pCO2 2000 MUatm). Parental pre-acclimation to pHT
      7.2 for 85 days reduced developmental rates even when larvae were raised under
      moderate and high pH conditions, whereas pre-acclimation to pHT 7.4 did not alter
      offspring performance. Microelectrode measurements and pharmacological inhibitor
      studies carried out on larval stages demonstrated that maintenance of alkaline
      gastric pH represents a substantial energy sink under acidified conditions that
      may contribute up to 30% to the total energy budget. CONCLUSION: Parental pre
      acclimation to acidification levels that are beyond the pH that is encountered by
      this population in its natural habitat (eg, pHT 7.2) negatively affected larval
      size and development, potentially through reduced energy transfer. Maintenance of
      alkaline gastric pH and reductions in maternal energy reserves probably
      constitute the main factors for a reduced juvenile recruitment of this marine
      keystone species under simulated OA.

PMID- 29660257
TI  - Catholyte-Free Electrocatalytic CO2 Reduction to Formate.
AB  - Electrochemical reduction of carbon dioxide (CO2 ) into value-added chemicals is
      a promising strategy to reduce CO2 emission and mitigate climate change. One of
      the most serious problems in electrocatalytic CO2 reduction (CO2 R) is the low
      solubility of CO2 in an aqueous electrolyte, which significantly limits the
      cathodic reaction rate. This paper proposes a facile method of catholyte-free
      electrocatalytic CO2 reduction to avoid the solubility limitation using
      commercial tin nanoparticles as a cathode catalyst. Interestingly, as the
      reaction temperature rises from 303 K to 363 K, the partial current density (PCD)
      of formate improves more than two times with 52.9 mA cm-2 , despite the decrease
      in CO2 solubility. Furthermore, a significantly high formate concentration of
      41.5 g L-1 is obtained as a one-path product at 343 K with high PCD (51.7 mA cm-2
      ) and high Faradaic efficiency (93.3 %) via continuous operation in a full flow
      cell at a low cell voltage of 2.2 V.

PMID- 29660258
TI  - Pleural tuberculosis: A concise clinical review.
AB  - Tuberculosis (TB) is the leading infectious cause of death worldwide, and the
      commonest cause of death in people living with HIV. Globally, pleural TB remains
      one of the most frequent causes of pleural exudates, particularly in TB-endemic
      areas and in the HIV positive population. Most TB pleural effusions are exudates
      with high adenosine deaminase (ADA), lymphocyte-rich, straw-coloured and free
      flowing, with a low yield on mycobacterial culture. TB pleurisy can also present
      as loculated neutrophil-predominant effusions which mimic parapneumonic
      effusions. Rarely, they can present as frank TB empyema, containing an abundance
      of mycobacteria. Up to 80% of patients have parenchymal involvement on chest
      imaging. The diagnosis is simple if M. tuberculosis is detected in sputum,
      pleural fluid or biopsy specimens, and the recent advent of liquid medium culture
      techniques has increased the microbiological yield dramatically. Where the
      prevalence of TB is high the presence of a lymphocyte-predominant exudate with a
      high ADA has a positive predictive value of 98%. In low prevalence areas, the
      absence of an elevated ADA and lymphocyte predominance makes TB very unlikely,
      and pleural biopsy should be performed to confirm the diagnosis. Pleural biopsy
      for liquid culture and susceptibility testing must also be considered where the
      prevalence of drug resistant TB is high. Treatment regimens are identical to
      those administered for pulmonary TB. Initial pleural drainage may have a role in
      symptom relief and in hastening the resolution of the effusion. Surgical
      intervention may be required in loculated effusions and empyemas.

PMID- 29660259
TI  - Hepatitis E seroprevalence in the Americas: A systematic review and meta
      analysis.
AB  - BACKGROUND & AIMS: While hepatitis E virus infections are a relevant topic in
      Europe, knowledge about epidemiology of hepatitis E virus infections in the USA
      and Latin America is still limited. Aim of this study was to estimate anti
      hepatitis E virus IgG seroprevalence in the Americas and to assess whether low
      socioeconomic status is associated with hepatitis E virus exposure. METHODS: We
      performed a systematic review and meta-analysis. Literature search was performed
      in PubMed for articles published 01/1994-12/2016. Prevalence was estimated using
      a mixed-effects model and reported in line with PRISMA reporting guidelines.
      RESULTS: Seroprevalence was significantly higher in the USA than in Latin
      America, independently of assay, patient cohort, methodological quality or study
      year (OR: 1.82 (1.06-3.08), P = .03). Patients in the USA had a more than doubled
      estimated seroprevalence (up to 9%, confidence interval 5%-15.6%) than those in
      Brazil (up to 4.2%, confidence interval 2.4%-7.1%; OR: 2.27 (1.25-4.13); P =
      .007) and Mixed Caribbean (up to 1%, OR: 8.33 (1.15-81.61); P = .04). A
      comparison with published data from Europe demonstrated that anti-hepatitis E
      virus seroprevalence in the USA and Europe did not differ significantly (OR: 1.33
      (0.81-2.19), P = .25), while rate in South America was significantly lower than
      that in Europe (OR: 0.67 (0.45-0.98), P = .04). CONCLUSIONS: Hepatitis E virus is
      common in the USA. Surprisingly, the risk of hepatitis E virus exposure was low
      in many South American countries. Seroprevalence did not differ significantly
      between Europe and the USA. Hence, hepatitis E virus is not limited to countries
      with low sanitary standards, and a higher socioeconomic status does not protect
      populations from hepatitis E virus exposure.

PMID- 29660260
TI  - 2-(4'-Pyridyl-N-oxide)-Substituted Hemithioindigos as Photoresponsive Guests for
      a Super Aryl-Extended Calix[4]pyrrole Receptor.
AB  - We report the synthesis of two 2-(4'-pyridyl-N-oxide)-substituted hemithioindigos
      (HTIs). We probed their photoisomerization by using UV/Vis and 1 H NMR
      spectroscopy techniques. Light irradiation at lambda=450 nm provoked the
      isomerization of the HTI Z isomer to the E counterpart to a large extent (~80 %
      at the photostationary state). 1 H NMR titration experiments revealed the
      formation of thermodynamically and kinetically stable 1:1 inclusion complexes of
      the (Z)-HTI isomers with a super aryl-extended host (association constant>104  m
      1 ). Photoirradiation at lambda=450 nm of the inclusion complexes induced the
      isomerization of the bound HTI N-oxide to afford the (E)-HTI?calix[4]pyrrole
      complex. We determined accurate association constant values for the 1:1 inclusion
      complexes of the (Z)- and (E)-HTI isomers by using isothermal titration
      calorimetry experiments. The results showed that the stability constants of the
      (E)-HTI complexes were 2.2-2.8-fold lower than those of the (Z)-HTI counterparts,
      which explains the lack of light-induced release of the former to the bulk
      solution.

PMID- 29660261
TI  - The novel KIR2DL1 allele, KIR2DL1*037, defined in the cell line SPO010 (IHW9036).
AB  - The novel KIR2DL1*037 allele discovered and characterised by single molecule real
      time (SMRT) DNA sequencing.

PMID- 29660262
TI  - Reactive Periostitis Due To Inhalant Abuse.

PMID- 29660263
TI  - Characteristics and long-term prognosis of patients with heart failure and mid
      range ejection fraction compared with reduced and preserved ejection fraction: a
      systematic review and meta-analysis.
AB  - AIMS: This study aimed to assess by a meta-analysis the clinical characteristics,
      all-cause and cardiovascular mortality, and hospitalization of patients with
      heart failure (HF) with mid-range ejection fraction (HFmrEF) compared with HF
      with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction
      (HFpEF). METHODS AND RESULTS: Data from 12 eligible observational studies
      including 109 257 patients were pooled. HFmrEF patients were significantly
      different and occupied a mid-position between HFrEF and HFpEF: mean age 73.6 +/-
      9.8 vs. 72.6 +/- 9.8 and 77.6 +/- 7.2 years, male gender 59% vs. 68.5% and 40%,
      ischaemic heart disease 49% vs. 52.6% and 39.4%, hypertension 67.3% vs. 61.5% and
      76.5%, atrial fibrillation 45.2% vs. 39.6% and 46%, chronic obstructive pulmonary
      disease 26.4% vs. 24.9% and 30.5%, estimated glomerular filtration rate 62 +/- 30
      vs. 63.3 +/- 23 and 59 +/- 22.5, use of renin-angiotensin system inhibitors 79.6%
      vs. 90.1% and 68.7%, beta-blockers 82% vs. 89% and 73.5%, and aldosterone
      antagonists 20.3 vs. 31.5% and 26%, P-values < 0.05. After a mean follow-up of 31
      +/- 5 months, all-cause mortality was significantly lower in HFmrEF than in HFrEF
      and HFpEF (26.8% vs. 29.5% and 31%): risk ratio (RR) 0.95 [0.93-0.98; 95%
      confidence interval (CI)], P < 0.001, and 0.97 (0.94-0.99; 95% CI), P = 0.014,
      respectively. Cardiovascular mortality was lowest in HFmrEF (9.7% vs. 13% and
      12.8%): RR = 0.81 (0.73-0.91), P < 0.001, and 1.10 (0.97-1.24; 95% CI), P = 0.13,
      respectively. HF hospitalization in HFmrEF compared to that in HFrEF and HFpEF
      was 23.9% vs. 27.6% and 23.3% with RR = 0.89 (0.85-0.93), P < 0.001, and RR =
      1.12 (1.07-1.17), P < 0.001, respectively. CONCLUSIONS: The results of this study
      support that HFmrEF is a distinct category characterized by a mid-position
      between HFrEF and HFpEF and with the lowest all-cause and cardiovascular
      mortality.

PMID- 29660264
TI  - Selective Fragmentation of Biorefinery Corncob Lignin into p-Hydroxycinnamic
      Esters with a Supported Zinc Molybdate Catalyst.
AB  - Lignin is the largest renewable resource of bioaromatics, and the catalytic
      fragmentation of lignin into phenolic monomers is increasingly recognized as an
      important starting point for lignin valorization. Herein, we report that ZnMoO4
      supported on MCM-41 can catalyze the fragmentation of biorefinery technical
      lignin, enzymatic mild acidolysis lignin, and native lignin derived from corncob
      to yield lignin oily products that contain 15-37.8 wt % phenolic monomers, in
      which the high selectivities towards methyl coumarate (1) and methyl ferulate (2)
      were obtained (up to 78 %). The effects of some key parameters such as the
      influence of the solvent, reaction temperature, time, H2 pressure, and catalyst
      dosage were examined in view of activity and selectivity. The loss of Zn from the
      catalyst is discussed as the primary cause of deactivation, and the catalytic
      activity and selectivity can be well preserved in at least six runs by thermal
      calcination. The high selectivity to 1 and 2 leads to their easy separation and
      purification from lignin oily product to provide sustainable monomers for the
      preparation of functional polyether esters and polyesters.

PMID- 29660265
TI  - Hypochlorite-Mediated Modulation of Photoinduced Electron Transfer in a
      Phenothiazine-Boron dipyrromethene Electron Donor-Acceptor Dyad: A Highly Water
      Soluble "Turn-On" Fluorescent Probe for Hypochlorite.
AB  - A highly water-soluble phenothiazine (PTZ)-boron dipyrromethene (BODIPY)-based
      electron donor-acceptor dyad (WS-Probe), which contains BODIPY as the signaling
      antennae and PTZ as the OCl- reactive group, was designed and used as a
      fluorescent chemosensor for the detection of OCl- . Upon addition of incremental
      amounts of NaOCl, the quenched fluorescence of WS-Probe was enhanced drastically,
      which indicated the inhibition of reductive photoinduced electron transfer (PET)
      from PTZ to 1 BODIPY*; the detection limit was calculated to be 26.7 nm.
      Selectivity studies with various reactive oxygen species, cations, and anions
      revealed that WS-Probe was able to detect OCl- selectively. Steady-state
      fluorescence studies performed at varied pH suggested that WS-Probe can detect
      NaOCl and exhibits maximum fluorescence in the pH range of 7 to 8, similar to
      physiological conditions. ESI-MS analysis and 1 H NMR spectroscopy titrations
      showed the formation of sulfoxide as the major oxidized product upon addition of
      hypochlorite. More interestingly, when WS-Probe was treated with real water
      samples, the fluorescence response was clearly visible with tap water and
      disinfectant, which indicated the presence of OCl- in these samples. The in vitro
      cell viability assay performed with human embryonic kidney 293 (HEK 293) cells
      suggested that WS-probe is non-toxic up to 10 MUm and implicates the use of the
      probe for biological applications.

PMID- 29660266
TI  - Role of Stem Cell-Like Memory T Cells in Systemic Lupus Erythematosus.
AB  - OBJECTIVE: Stem cell-like memory T (Tscm) cells are long-lived memory T cells
      that have multipotent capacity to differentiate into different subsets. However,
      the role of Tscm cells in autoimmune diseases remains unclear. Here, we performed
      phenotypic studies to identify Tscm cells in patients experiencing systemic lupus
      erythematosus (SLE). METHODS: CD4+ and CD8+ Tscm cells were identified in SLE
      patients and healthy controls (HCs). In in vitro culture systems, CD4+ Tscm cells
      were induced to differentiate into subsets of T cells, including follicular
      helper T (Tfh) cells, and cytokine production patterns were assessed after
      stimulation. After confirming induction of transcription factors for Tfh cells,
      the capacity of CD4+ Tscm-derived Tfh cells to help B cells was analyzed by
      measuring antibody secretion. RESULTS: The percentages of CD4+ and CD8+ Tscm
      cells among the naive CD4+/CD8+ or total CD4+ T cell populations were
      significantly higher in SLE patients than in HCs. Stimulated Tscm cells from SLE
      patients could replenish themselves and differentiate into other T lymphocyte
      subsets, including Tfh cells upon stimulation with T cell receptor. Production of
      T cell factor 1, which is an inducer of Tfh, was also increased. The
      differentiated Tfh cells increased antibody production by autologous B cells.
      CONCLUSION: Taken together, these findings suggest that Tscm cells play a role in
      the pathogenesis of SLE by maintaining Tfh cells.

PMID- 29660267
TI  - Recovery process and determinants of adverse event occurrence in bronchoscopic
      procedures performed under general anaesthesia.
AB  - OBJECTIVE: Regarding the fact that rigid bronchoscopy is generally performed
      under general anaesthesia and this patient subgroup is remarkably morbid,
      encountering procedure and/or anaesthesia related complications are highly
      likely. Here, we aimed to assess factors influencing recovery and detect possible
      determinants of adverse event occurrence during these operations performed in a
      tertiary referral centre. METHODS: Eighty-one consecutive ASA I-IV patients were
      recruited for this investigation. In the operating theatre after induction of
      anaesthesia and advancement of the device, maintenance was provided with total
      intravenous anaesthesia. Neuromuscular blockage was invariably administered, and
      patients were ventilated manually. In addition to preoperative demographic and
      procedural characteristics, perioperative hemodynamic variables, recovery times
      and observed adverse events were noted. RESULTS: Basic demographic properties,
      ASA and Mallampati scores, and procedure specific variables as lesion
      localization, lesion and procedure type were comparable among groups assembled
      with reference to event occurrence. Patients who had experienced adverse event
      had higher heart rates. Recovery times were comparable between Event (-) and
      Event (+) groups. Relationship of recovery process were individually tested with
      all variables and only lesion type was detected to have an effect on respiration
      and extubation times. Among all parameters only procedural time seemed to be
      associated with adverse event occurrence (mins, 22.9 +/- 11.9 vs 41.6 +/- 28.8, P
      < .001). CONCLUSION: Recovery times related with return of spontaneous
      respiration were significantly lower in procedures performed for treatment of
      tumoral diseases in this study and procedure length was determined to be the
      ultimate factor which had an impact on adverse event occurrence.

PMID- 29660268
TI  - Ultradeep Palmitoylomics Enabled by Dithiodipyridine-Functionalized Magnetic
      Nanoparticles.
AB  - Palmitoylation, a type of fatty acylation, has vital roles in many biological
      processes. For ultradeep identification of protein palmitoylation, an enrichment
      approach based on a novel magnetic microsphere modified with 2,2'
      dithiodipyridine (Fe3O4/SiO2-SSPy microsphere) is presented in this study. The
      Fe3O4/SiO2-SSPy microspheres were synthesized by directly coating thiol
      containing silane coupling agent onto the magnetic supraparticles in aqueous
      solution at room temperature. Due to the intrinsic magnetic properties, high
      surface-to-volume ratios, and abundant reactive functional groups on the surface,
      these microspheres enabled direct capture of palmitoylated targets and convenient
      isolation, contributing to remarkable enrichment selectivity (purifying
      palmitoylated peptides from mixtures with nonpalmitoylated peptides even at a
      1:500 molar ratio) and sensitivity (the detection limit was at femtomole level),
      thus enabling a global annotation of protein palmitoylation for complex
      biological samples. We successfully identified 1304 putative palmitoylated
      proteins from mouse brain tissues by using this method, which is the largest
      mouse palmitoylome data set to date. Except for those known members, many new
      proteins and pathways were also found to be regulated by palmitoylation.

PMID- 29660269
TI  - Deterministic Encapsulation of Human Cardiac Stem Cells in Variable Composition
      Nanoporous Gel Cocoons To Enhance Therapeutic Repair of Injured Myocardium.
AB  - Although cocooning explant-derived cardiac stem cells (EDCs) in protective
      nanoporous gels (NPGs) prior to intramyocardial injection boosts long-term cell
      retention, the number of EDCs that finally engraft is trivial and unlikely to
      account for salutary effects on myocardial function and scar size. As such, we
      investigated the effect of varying the NPG content within capsules to alter the
      physical properties of cocoons without influencing cocoon dimensions. Increasing
      NPG concentration enhanced cell migration and viability while improving cell
      mediated repair of injured myocardium. Given that the latter occurred with NPG
      content having no detectable effect on the long-term engraftment of transplanted
      cells, we found that changing the physical properties of cocoons prompted explant
      derived cardiac stem cells to produce greater amounts of cytokines, nanovesicles,
      and microRNAs that boosted the generation of new blood vessels and new
      cardiomyocytes. Thus, by altering the physical properties of cocoons by varying
      NPG content, the paracrine signature of encapsulated cells can be enhanced to
      promote greater endogenous repair of injured myocardium.

PMID- 29660270
TI  - Protective Effect of a Mitochondria-Targeted Peptide against the Development of
      Chemotherapy-Induced Peripheral Neuropathy in Mice.
AB  - Several chemotherapeutic agents used for cancer treatment induce dose-limiting
      peripheral neuropathy that compromises patients' quality of life and limits
      cancer treatment. Recently, mitochondrial dysfunction has been shown to be
      involved in the mechanism of chemotherapy-induced peripheral neuropathy. SS-20 is
      a mitochondria-targeted peptide that promotes mitochondrial respiration and
      restores mitochondrial bioenergetics. In the present study, we examined the
      protective effect of SS-20 against the development of chemotherapy-induced
      peripheral neuropathy utilizing a murine model of peripheral neuropathy induced
      by oxaliplatin, a first-line chemotherapy agent for colon cancer. Weekly
      administrations of oxaliplatin induced peripheral neuropathy as demonstrated by
      the development of neuropathic pain and loss of intraepidermal nerve fibers in
      the hind paw. Continuous administration of SS-20 protected against the
      development of oxaliplatin-induced neuropathic pain and mitigated the loss of
      intraepidermal nerve fibers to normal levels. Our findings suggest that SS-20 may
      be a drug candidate for the prevention of chemotherapy-induced peripheral
      neuropathy.

PMID- 29660271
TI  - Denaturation via Surfactants Changes Composition of Protein Corona.
AB  - The use of nanocarriers as drug delivery vehicles brings them into contact with
      blood plasma proteins. Polymeric nanocarriers require some sort of surfactant to
      ensure colloidal stability. Formation of the protein corona is therefore
      determined not only by the intrinsic properties of the nanocarrier itself but
      also by the accompanying surfactant. Although it is well-known that surfactants
      have an impact on protein structure, only few studies were conducted on the
      specific effect of surfactants on the composition of protein corona of
      nanocarriers. Therefore, we analyzed the composition of the protein corona on
      "stealth" nanoparticles with additional surfactant (cetyltrimethylammonium
      chloride, CTMA-Cl) after plasma incubation. Additional CTMA-Cl led to an
      enrichment of apolipoprotein-A1 and vitronectin in the corona, while less
      clusterin could be found. Further, the structural stability of apolipoprotein-A1
      and clusterin was monitored for a wide range of CTMA-Cl concentrations. Clusterin
      turned out to be more sensitive to CTMA-Cl, with denaturation occurring at lower
      concentrations.

PMID- 29660272
TI  - Force Field for Water over Pt(111): Development, Assessment, and Comparison.
AB  - Metal/water interfaces are key in many natural and industrial processes, such as
      corrosion, atmospheric, or environmental chemistry. Even today, the only
      practical approach to simulate large interfaces between a metal and water is to
      perform force-field simulations. In this work, we propose a novel force field,
      GAL17, to describe the interaction of water and a Pt(111) surface. GAL17 builds
      on three terms: (i) a standard Lennard-Jones potential for the bonding
      interaction between the surface and water, (ii) a Gaussian term to improve the
      surface corrugation, and (iii) two terms describing the angular dependence of the
      interaction energy. The 12 parameters of this force field are fitted against a
      set of 210 adsorption geometries of water on Pt(111). The performance of GAL17 is
      compared to several other approaches that have not been validated against
      extensive first-principles computations yet. Their respective accuracy is
      evaluated on an extended set of 802 adsorption geometries of H2O on Pt(111), 52
      geometries derived from icelike layers, and an MD simulation of an interface
      between a c(4 * 6) Pt(111) surface and a water layer of 14 A thickness. The newly
      developed GAL17 force field provides a significant improvement over previously
      existing force fields for Pt(111)/H2O interactions. Its well-balanced performance
      suggests that it is an ideal candidate to generate relevant geometries for the
      metal/water interface, paving the way to a representative sampling of the
      equilibrium distribution at the interface and to predict solvation free energies
      at the solid/liquid interface.

PMID- 29660273
TI  - Rapid Calculation of Molecular Kinetics Using Compressed Sensing.
AB  - Recent methods for the analysis of molecular kinetics from massive molecular
      dynamics (MD) data rely on the solution of very large eigenvalue problems. Here
      we build upon recent results from the field of compressed sensing and develop the
      spectral oASIS method, a highly efficient approach to approximate the leading
      eigenvalues and eigenvectors of large generalized eigenvalue problems without
      ever having to evaluate the full matrices. The approach is demonstrated to reduce
      the dimensionality of the problem by 1 or 2 orders of magnitude, directly leading
      to corresponding savings in the computation and storage of the necessary matrices
      and a speedup of 2 to 4 orders of magnitude in solving the eigenvalue problem. We
      demonstrate the method on extensive data sets of protein conformational changes
      and protein-ligand binding using the variational approach to conformation
      dynamics (VAC) and time-lagged independent component analysis (TICA). Our
      approach can also be applied to kernel formulations of VAC, TICA, and extended
      dynamic mode decomposition (EDMD).

PMID- 29660274
TI  - Plane-Wave Implementation and Performance of a-la-Carte Coulomb-Attenuated
      Exchange-Correlation Functionals for Predicting Optical Excitation Energies in
      Some Notorious Cases.
AB  - Linear-response time-dependent density functional theory (LR-TD-DFT) has become a
      valuable tool in the calculation of excited states of molecules of various sizes.
      However, standard generalized-gradient approximation and hybrid exchange
      correlation (xc) functionals often fail to correctly predict charge-transfer (CT)
      excitations with low orbital overlap, thus limiting the scope of the method. The
      Coulomb-attenuation method (CAM) in the form of the CAM-B3LYP functional has been
      shown to reliably remedy this problem in many CT systems, making accurate
      predictions possible. However, in spite of a rather consistent performance across
      different orbital overlap regimes, some pitfalls remain. Here, we present a fully
      flexible and adaptable implementation of the CAM for Gamma-point calculations
      within the plane-wave pseudopotential molecular dynamics package CPMD and explore
      how customized xc functionals can improve the optical spectra of some notorious
      cases. We find that results obtained using plane waves agree well with those from
      all-electron calculations employing atom-centered bases, and that it is possible
      to construct a new Coulomb-attenuated xc functional based on simple
      considerations. We show that such a functional is able to outperform CAM-B3LYP in
      some cases, while retaining similar accuracy in systems where CAM-B3LYP performs
      well.

PMID- 29660275
TI  - Entrapped Single Tungstate Site in Zeolite for Cooperative Catalysis of Olefin
      Metathesis with Bronsted Acid Site.
AB  - Industrial olefin metathesis catalysts generally suffer from low reaction rates
      and require harsh reaction conditions for moderate activities. This is due to
      their inability to prevent metathesis active sites (MASs) from aggregation and
      their intrinsic poor adsorption and activation of olefin molecules. Here,
      isolated tungstate species as single molecular MASs are immobilized inside
      zeolite pores by Bronsted acid sites (BASs) on the inner surface. It is
      demonstrated that unoccupied BASs in atomic proximity to MASs enhance olefin
      adsorption and facilitate the formation of metallocycle intermediates in a
      stereospecific manner. Thus, effective cooperative catalysis takes place over the
      BAS-MAS pair inside the zeolite cavity. In consequence, for the cross-metathesis
      of ethene and trans-2-butene to propene, under mild reaction conditions, the
      propene production rate over WO x/USY is ca. 7300 times that over the industrial
      WO3/SiO2-based catalyst. A propene yield up to 79% (80% selectivity) without
      observable deactivation was obtained over WO x/USY for a wide range of reaction
      conditions.

PMID- 29660276
TI  - Combined Approach of Backbone Amide Linking and On-Resin N-Methylation for the
      Synthesis of Bioactive and Metabolically Stable Peptides.
AB  - Rhabdopeptides are a large class of nonribosomal peptides from the bacteria
      Xenorhabdus and Photorhabdus with low micromolar activity against different
      protozoa, which are the causative agents of several tropical diseases. The
      development of a facile and flexible synthesis combining backbone amide linking
      with on-resin peralkylation for the synthesis of permethylated rhabdopeptides is
      described. This strategy allows the fast generation of permethylated naturally
      occurring and artificial rhabdopeptides for a structure-activity study.
      Furthermore, in vitro experiments revealed their superior properties regarding
      their stability and passive membrane diffusion.

PMID- 29660278
TI  - Transient Charge and Energy Flow in the Wide-Band Limit.
AB  - The wide-band limit is a commonly used approximation to analyze transport through
      nanoscale devices. In this work we investigate its applicability to the study of
      charge and heat transport through molecular break junctions exposed to voltage
      biases and temperature gradients. We find by comparative simulations that while
      the wide-band-limit approximation faithfully describes the long-time charge and
      heat transport, it fails to characterize the short-time behavior of the junction.
      In particular, we show that the charge current flowing through the device shows a
      discontinuity when a temperature gradient is applied, while the energy flow is
      discontinuous when a voltage bias is switched on and even diverges when the
      junction is exposed to both a temperature gradient and a voltage bias. We provide
      an explanation for this pathological behavior and propose two possible solutions
      to this problem.

PMID- 29660277
TI  - Dendrimersomes Exhibit Lamellar-to-Sponge Phase Transitions.
AB  - Lamellar to nonlamellar membrane shape transitions play essential roles in key
      cellular processes, such as membrane fusion and fission, and occur in response to
      external stimuli, including drug treatment and heat. A subset of these
      transitions can be modeled by means of thermally inducible amphiphile assemblies.
      We previously reported on mixtures of hydrogenated, fluorinated, and hybrid Janus
      dendrimers (JDs) that self-assemble into complex dendrimersomes (DMSs), including
      dumbbells, and serve as promising models for understanding the complexity of
      biological membranes. Here we show, by means of a variety of complementary
      techniques, that DMSs formed by single JDs or by mixtures of JDs undergo a
      thermally induced lamellar-to-sponge transition. Consistent with the formation of
      a three-dimensional bilayer network, we show that DMSs become more permeable to
      water-soluble fluorophores after transitioning to the sponge phase. These DMSs
      may be useful not only in modeling isotropic membrane rearrangements of
      biological systems but also in drug delivery since nonlamellar delivery vehicles
      can promote endosomal disruption and cargo release.

PMID- 29660279
TI  - HOMO Level Pinning in Molecular Junctions: Joint Theoretical and Experimental
      Evidence.
AB  - A central issue in molecular electronics in order to build functional devices is
      to assess whether changes in the electronic structure of isolated compounds by
      chemical derivatization are retained once the molecules are inserted into
      molecular junctions. Recent theoretical studies have suggested that this is not
      always the case due to the occurrence of pinning effects making the alignment of
      the transporting levels insensitive to the changes in the electronic structure of
      the isolated systems. We explore here this phenomenon by investigating at both
      the experimental and theoretical levels the I/ V characteristics of molecular
      junctions incorporating three different three-ring phenylene ethynylene
      derivatives designed to exhibit a significant variation of the HOMO level in the
      isolated state. At the theoretical level, our NEGF/DFT calculations performed on
      junctions including the three compounds show that, whereas the HOMO of the
      molecules varies by 0.61 eV in the isolated state, their alignment with respect
      to the Fermi level of the gold electrodes in the junction is very similar (within
      0.1 eV). At the experimental level, the SAMs made of the three compounds have
      been contacted by a conducting AFM probe to measure their I/ V characteristics.
      The alignment of the HOMO with respect to the Fermi level of the gold electrodes
      has been deduced by fitting the I/ V curves, using a model based on a single
      level description (Newns-Anderson model). The extracted values are found to be
      very similar for the three derivatives, in full consistency with the theoretical
      predictions, thus providing clear evidence for a HOMO level pinning effect.

PMID- 29660280
TI  - Comparison of Linear and Hyperbranched Polyether Lipids for Liposome Shielding by
      18F-Radiolabeling and Positron Emission Tomography.
AB  - Multifunctional and highly biocompatible polyether structures play a key role in
      shielding liposomes from degradation in the bloodstream, providing also multiple
      functional groups for further attachment of targeting moieties. In this work
      hyperbranched polyglycerol ( hbPG) bearing lipids with long alkyl chain anchor
      are evaluated with respect to steric stabilization of liposomes. The branched
      polyether lipids possess a hydrophobic bis(hexadecyl)glycerol membrane anchor for
      the liposomal membrane. hbPG was chosen as a multifunctional alternative to PEG,
      enabling the eventual linkage of multiple targeting vectors. Different hbPG
      lipids ( Mn = 2900 and 5200 g mol-1) were examined. A linear
      bis(hexadecyl)glycerol-PEG lipid ( Mn = 3000 g mol-1) was investigated as well,
      comparing hbPG and PEG with respect to shielding properties. Radiolabeling of the
      polymers was carried out using 1-azido-2-(2-(2-[18F]fluoroethoxy)ethoxy)ethane
      ([18F]F-TEG-N)3 via copper-catalyzed alkyne-azide cycloaddition with excellent
      radiochemical yields exceeding 95%. Liposomes were prepared by the thin-film
      hydration method followed by repeated extrusion. Use of a custom automatic
      extrusion device gave access to reproducible sizes of the liposomes (hydrodynamic
      radius of 60-94 nm). The in vivo fate of the bis(hexadecyl)glycerol polyethers
      and their corresponding assembled liposome structures were evaluated via
      noninvasive small animal positron emission tomography (PET) imaging and
      biodistribution studies (1 h after injection and 4 h after injection) in mice.
      Whereas the main uptake of the nonliposomal polyether lipids was observed in the
      kidneys and in the bladder after 1 h due to rapid renal clearance, in contrast,
      the corresponding liposomes showed uptake in the blood pool as well as in organs
      with good blood supply, that is, heart and lung over the whole observation period
      of 4 h. The in vivo behavior of all three liposomal formulations was comparable,
      albeit with remarkable differences in splenic uptake. Overall, liposomes shielded
      by the branched polyglycerol lipids show a favorable biodistribution with greatly
      prolonged blood circulation times, rendering them promising novel nanovesicles
      for drug transport and targeting.

PMID- 29660281
TI  - Grand Canonical Investigation of the Quasi Liquid Layer of Ice: Is It Liquid?
AB  - In this study, the solid-vapor equilibrium and the quasi liquid layer (QLL) of
      ice Ih exposing the basal and primary prismatic faces were explored by means of
      grand canonical molecular dynamics simulations with the monatomic mW potential.
      For this model, the solid-vapor equilibrium was found to follow the Clausius
      Clapeyron relation in the range examined, from 250 to 270 K, with a Delta Hsub of
      50 kJ/mol in excellent agreement with the experimental value. The phase diagram
      of the mW model was constructed for the low pressure region around the triple
      point. The analysis of the crystallization dynamics during condensation and
      evaporation revealed that, for the basal face, both processes are highly
      activated, and in particular cubic ice is formed during condensation, producing
      stacking-disordered ice. The basal and primary prismatic surfaces of ice Ih were
      investigated at different temperatures and at their corresponding equilibrium
      vapor pressures. Our results show that the region known as QLL can be interpreted
      as the outermost layers of the solid where a partial melting takes place. Solid
      islands in the nanometer length scale are surrounded by interconnected liquid
      areas, generating a bidimensional nanophase segregation that spans throughout the
      entire width of the outermost layer even at 250 K. Two approaches were adopted to
      quantify the QLL and discussed in light of their ability to reflect this
      nanophase segregation phenomena. Our results in the MUVT ensemble were compared
      with NPT and NVT simulations for two system sizes. No significant differences
      were found between the results as a consequence of model system size or of the
      working ensemble. Nevertheless, certain advantages of performing MUVT simulations
      in order to reproduce the experimental situation are highlighted. On the one
      hand, the QLL thickness measured out of equilibrium might be affected because of
      crystallization being slower than condensation. On the other, preliminary
      simulations of AFM indentation experiments show that the tip can induce capillary
      condensation over the ice surface, enlarging the apparent QLL.

PMID- 29660282
TI  - Design, (Radio)Synthesis, and in Vitro and in Vivo Evaluation of Highly Selective
      and Potent Matrix Metalloproteinase 12 (MMP-12) Inhibitors as Radiotracers for
      Positron Emission Tomography.
AB  - Dysregulated levels of activated matrix metalloproteinases (MMPs) are linked to
      different pathologies, such as cancer, atherosclerosis, neuroinflammation, and
      arthritis. Therefore, imaging of MMPs with positron-emission tomography (PET)
      represents a powerful tool for the diagnosis of MMP-associated diseases.
      Moreover, to distinguish between the distinct functions and roles of individual
      MMPs in particular pathophysiological processes, their specific imaging must be
      realized with radiolabeled tracers, such as fluorine-18-labeled MMP inhibitors
      (MMPIs). Therefore, fluorinated dibenzofuransulfonamide-based MMPIs showing
      excellent inhibition of MMP-12 and selectivity for MMP-12 over other MMPs were
      prepared. MMP-12 is a key enzyme in diseases such as chronic obstructive
      pulmonary disease (COPD) and atherosclerosis. Because of their promising in vitro
      properties, three candidates (4, 9, and 19) were selected from this library, and
      radiofluorinated analogues ([18F]4, [18F]9, and [18F]19) were successfully
      synthesized. Initial in vitro serum stability and in vivo biodistribution studies
      of the radiolabeled MMPIs with PET demonstrated their potential benefit for
      preferable MMP-12 imaging.

PMID- 29660283
TI  - Genotoxicity Assessment of Drinking Water Disinfection Byproducts by DNA Damage
      and Repair Pathway Profiling Analysis.
AB  - Genotoxicity is considered a major concern for drinking water disinfection
      byproducts (DBPs). Of over 700 DBPs identified to date, only a small number has
      been assessed with limited information for DBP genotoxicity mechanism(s). In this
      study, we evaluated genotoxicity of 20 regulated and unregulated DBPs applying a
      quantitative toxicogenomics approach. We used GFP-fused yeast strains that
      examine protein expression profiling of 38 proteins indicative of all known DNA
      damage and repair pathways. The toxicogenomics assay detected genotoxicity
      potential of these DBPs that is consistent with conventional genotoxicity assays
      end points. Furthermore, the high-resolution, real-time pathway activation and
      protein expression profiling, in combination with clustering analysis, revealed
      molecular level details in the genotoxicity mechanisms among different DBPs and
      enabled classification of DBPs based on their distinct DNA damage effects and
      repair mechanisms. Oxidative DNA damage and base alkylation were confirmed to be
      the main molecular mechanisms of DBP genotoxicity. Initial exploration of QSAR
      modeling using moleular genotoxicity end points (PELI) suggested that
      genotoxicity of DBPs in this study was correlated with topological and quantum
      chemical descriptors. This study presents a toxicogenomics-based assay for fast
      and efficient mechanistic genotoxicity screening and assessment of a large number
      of DBPs. The results help to fill in the knowledge gap in the understanding of
      the molecular mechanisms of DBP genotoxicity.

PMID- 29660284
TI  - Nonmicrobicidal Small Molecule Inhibition of Polysaccharide Metabolism in Human
      Gut Microbes: A Potential Therapeutic Avenue.
AB  - A new approach for the nonmicrobicidal phenotypic manipulation of prominent
      gastrointestinal microbes is presented. Low micromolar concentrations of a
      chemical probe, acarbose, can selectively inhibit the Starch Utilization System
      and ablate the ability of Bacteroides thetaiotaomicron and B. fragilis strains to
      metabolize potato starch and pullulan. This strategy has potential therapeutic
      relevance for the selective modulation of the GI microbiota in a nonmicrobicidal
      manner.

PMID- 29660285
TI  - Pseudotargeted MS Method for the Sensitive Analysis of Protein Phosphorylation in
      Protein Complexes.
AB  - In this study, we presented an enrichment-free approach for the sensitive
      analysis of protein phosphorylation in minute amounts of samples, such as
      purified protein complexes. This method takes advantage of the high sensitivity
      of parallel reaction monitoring (PRM). Specifically, low confident
      phosphopeptides identified from the data-dependent acquisition (DDA) data set
      were used to build a pseudotargeted list for PRM analysis to allow the
      identification of additional phosphopeptides with high confidence. The
      development of this targeted approach is very easy as the same sample and the
      same LC-system were used for the discovery and the targeted analysis phases. No
      sample fractionation or enrichment was required for the discovery phase which
      allowed this method to analyze minute amount of sample. We applied this
      pseudotargeted MS method to quantitatively examine phosphopeptides in affinity
      purified endogenous Shc1 protein complexes at four temporal stages of EGF
      signaling and identified 82 phospho-sites. To our knowledge, this is the highest
      number of phospho-sites identified from the protein complexes. This
      pseudotargeted MS method is highly sensitive in the identification of low
      abundance phosphopeptides and could be a powerful tool to study phosphorylation
      regulated assembly of protein complex.

PMID- 29660286
TI  - Visualization of Nanoplasmonic Coupling to Molecular Orbital in Light Emission
      Induced by Tunneling Electrons.
AB  - The coupling between localized plasmon and molecular orbital in the light
      emission from a metallic nanocavity has been directly detected and imaged with
      sub-0.1 nm resolution. The light emission intensity was enhanced when the energy
      difference between the tunneling electrons and the lowest unoccupied molecular
      orbital (LUMO) of an azulene molecule matches the energy of a plasmon mode of the
      nanocavity defined by the Ag-tip and Ag (110) substrate of a scanning tunneling
      microscope (STM). The spatially resolved image of the light emission intensity
      matches the spatial distribution of the LUMO obtained by scanning tunneling
      spectroscopy (STS) and density functional theory (DFT) calculations. Our results
      highlight the near-field coupling of a molecular orbital to the radiative decay
      of a plasmonic excitation in a confined nanoscale junction.

PMID- 29660288
TI  - Atomic Orbital Implementation of Extended Symmetry-Adapted Perturbation Theory
      (XSAPT) and Benchmark Calculations for Large Supramolecular Complexes.
AB  - We report an implementation of extended symmetry-adapted perturbation theory
      (XSAPT) in the atomic orbital basis, extending this method to systems where the
      monomers are large. In our "XSAPT(KS)" approach, monomers are described using
      range-separated Kohn-Sham (KS) density functional theory (DFT), with correct
      asymptotic behavior set by tuning the range-separation parameter omega in a
      monomer-specific way. This is accomplished either by conventional ionization
      potential (IP)-based tuning, in which omega is adjusted to satisfy the condition
      epsilonHOMO(omega) = -IP(omega), or else using a "global density-dependent" (GDD)
      condition, in which omega is fixed based on the size of the exchange hole. The
      latter procedure affords better results for both total interaction energies and
      energy components, when used in conjunction with our third-generation pairwise
      atom-atom dispersion potential (+ aiD3). Three-body (triatomic) dispersion terms
      are found to be important when the monomers are large, and we incorporate these
      by means of an Axilrod-Teller-Muto term, Edisp,3BATM, which reduces errors in
      supramolecular interaction energies by about a factor of 2. The XSAPT(KS) + aiD3
      + Edisp,3BATM(omegaGDD) approach affords mean absolute errors as low as 1.2 and
      4.2 kcal/mol, respectively, for the L7 and S12L benchmark test sets of large
      dimers. Such errors are comparable to those afforded by far more expensive
      methods, such as DFT-SAPT, and the closely related second-order perturbation
      theory with coupled dispersion (MP2C). We also survey the performance of various
      other quantum-chemical methods for these data sets and identify several
      semiempirical and DFT-based approaches whose accuracy approaches that of MP2C, at
      dramatically reduced cost.

PMID- 29660287
TI  - A Trimethoprim Conjugate of Thiomaltose Has Enhanced Antibacterial Efficacy In
      Vivo.
AB  - Trimethoprim is one of the most widely used antibiotics in the world. However,
      its efficacy is frequently limited by its poor water solubility and dose limiting
      toxicity. Prodrug strategies based on conjugation of oligosaccharides to
      trimethoprim have great potential for increasing the solubility of trimethoprim
      and lowering its toxicity, but they have been challenging to develop due to the
      sensitivity of trimethoprim to chemical modifications, and the rapid degradation
      of oligosaccharides in serum. In this report, we present a trimethoprim conjugate
      of maltodextrin termed TM-TMP, which increased the water solubility of
      trimethoprim by over 100 times, was stable to serum enzymes, and was active
      against urinary tract infections in mice. TM-TMP is composed of thiomaltose
      conjugated to trimethoprim, via a self-immolative disulfide linkage, and releases
      4'-OH-trimethoprim (TMP-OH) after disulfide cleavage, which is a known metabolic
      product of trimethoprim and is as potent as trimethoprim. TM-TMP also contains a
      new maltodextrin targeting ligand composed of thiomaltose, which is stable to
      hydrolysis by serum amylases and therefore has the metabolic stability needed for
      in vivo use. TM-TMP has the potential to significantly improve the treatment of a
      wide number of infections given its high water solubility and the widespread use
      of trimethoprim.

PMID- 29660289
TI  - Can Glycation Reduce Food Allergenicity?
AB  - As a naturally occurring reaction during food processing, glycation, also known
      as non-enzymatic browning or Maillard reaction, can improve food protein
      physiochemical properties and functionality. In this perspective, three aspects
      of glycation (terminology confusion between glycation and glycosylation, its
      current application, and its impact on immunoreactivity) are elaborated. Overall,
      the immunoreactivity of glycated proteins may decrease, remain unchanged, or even
      increase after food glycation. Also, it should be noted that the effect of
      glycation on the immunoglobulin (Ig)E- or IgG-binding capacity of allergens does
      not necessarily and correctly predict the allergenicity of the glycated protein
      in the allergic patient population.

PMID- 29660291
TI  - The Molecular Mechanism Underlying Ligand Binding to the Membrane-Embedded Site
      of a G-Protein-Coupled Receptor.
AB  - The crystal structure of P2Y1 receptor (P2Y1R), a class A GPCR, revealed a
      special extra-helical site for its antagonist, BPTU, which locates in-between the
      membrane and the protein. However, due to the limitation of crystallization
      experiments, the membrane was mimicked by use of detergents, and the information
      related to the binding of BPTU to the receptor in the membrane environment is
      rather limited. In the present work, we conducted a total of ~7.5 MUs all-atom
      simulations in explicit solvent using conventional molecular dynamics and
      multiple enhanced sampling methods, with models of BPTU and a POPC bilayer, both
      in the absence and presence of P2Y1R. Our simulations revealed that BPTU prefers
      partitioning into the interface of polar/lipophilic region of the lipid bilayer
      before associating with the receptor. Then, it interacts with the second
      extracellular loop of the receptor and reaches the binding site through the lipid
      receptor interface. In addition, by use of funnel-metadynamics simulations which
      efficiently enhance the sampling of bound and unbound states, we provide a
      statistically accurate description of the underlying binding free energy
      landscape. The calculated absolute ligand-receptor binding affinity is in
      excellent agreement with the experimental data (Delta Gb0_theo = -11.5 kcal mol
      1, Delta Gb0_exp= -11.7 kcal mol-1). Our study broadens the view of the current
      experimental/theoretical models and our understanding of the protein-ligand
      recognition mechanism in the lipid environment. The strategy used in this work is
      potentially applicable to investigate ligands association/dissociation with other
      membrane-embedded sites, allowing identification of compounds targeting membrane
      receptors of pharmacological interest.

PMID- 29660290
TI  - Effects of High-Pressure Treatment on the Muscle Proteome of Hake by Bottom-Up
      Proteomics.
AB  - A bottom-up proteomics approach was applied for the study of the effects of high
      pressure (HP) treatment on the muscle proteome of fish. The performance of the
      approach was established for a previous HP treatment (150-450 MPa for 2 min) on
      frozen (up to 5 months at -10  degrees C) European hake ( Merluccius merluccius).
      Concerning possible protein biomarkers of quality changes, a significant
      degradation after applying a pressure >=430 MPa could be observed for
      phosphoglycerate mutase-1, enolase, creatine kinase, fructose bisphosphate
      aldolase, triosephosphate isomerase, and nucleoside diphosphate kinase; contrary,
      electrophoretic bands assigned to tropomyosin, glyceraldehyde-3-phosphate
      dehydrogenase, and beta parvalbumin increased their intensity after applying a
      pressure >=430 MPa. This repository of potential protein biomarkers may be very
      useful for further HP investigations related to fish quality.

PMID- 29660292
TI  - Two-Level Chebyshev Filter Based Complementary Subspace Method: Pushing the
      Envelope of Large-Scale Electronic Structure Calculations.
AB  - We describe a novel iterative strategy for Kohn-Sham density functional theory
      calculations aimed at large systems (>1,000 electrons), applicable to metals and
      insulators alike. In lieu of explicit diagonalization of the Kohn-Sham
      Hamiltonian on every self-consistent field (SCF) iteration, we employ a two-level
      Chebyshev polynomial filter based complementary subspace strategy to (1) compute
      a set of vectors that span the occupied subspace of the Hamiltonian; (2) reduce
      subspace diagonalization to just partially occupied states; and (3) obtain those
      states in an efficient, scalable manner via an inner Chebyshev filter iteration.
      By reducing the necessary computation to just partially occupied states and
      obtaining these through an inner Chebyshev iteration, our approach reduces the
      cost of large metallic calculations significantly, while eliminating subspace
      diagonalization for insulating systems altogether. We describe the implementation
      of the method within the framework of the discontinuous Galerkin (DG) electronic
      structure method and show that this results in a computational scheme that can
      effectively tackle bulk and nano systems containing tens of thousands of
      electrons, with chemical accuracy, within a few minutes or less of wall clock
      time per SCF iteration on large-scale computing platforms. We anticipate that our
      method will be instrumental in pushing the envelope of large-scale ab initio
      molecular dynamics. As a demonstration of this, we simulate a bulk silicon system
      containing 8,000 atoms at finite temperature, and obtain an average SCF step wall
      time of 51 s on 34,560 processors; thus allowing us to carry out 1.0 ps of ab
      initio molecular dynamics in approximately 28 h (of wall time).

PMID- 29660293
TI  - Direct Observation of Cr3+ 3d States in Ruby: Toward Experimental Mechanistic
      Evidence of Metal Chemistry.
AB  - The role of transition metals in chemical reactions is often derived from probing
      the metal 3d states. However, the relation between metal site geometry and 3d
      electronic states, arising from multielectronic effects, makes the spectral data
      interpretation and modeling of these optical excited states a challenge. Here we
      show, using the well-known case of red ruby, that unique insights into the
      density of transition metal 3d excited states can be gained with 2p3d resonant
      inelastic X-ray scattering (RIXS). We compare the experimental determination of
      the 3d excited states of Cr3+ impurities in Al2O3 with 190 meV resolution 2p3d
      RIXS to optical absorption spectroscopy and to simulations. Using the crystal
      field multiplet theory, we calculate jointly for the first time the Cr3+
      multielectronic states, RIXS, and optical spectra based on a unique set of
      parameters. We demonstrate that (i) anisotropic 3d multielectronic interactions
      causes different scaling of Slater integrals, and (ii) a previously not observed
      doublet excited state exists around 3.35 eV. These results allow to discuss the
      influence of interferences in the RIXS intermediate state, of core-hole lifetime
      broadenings, and of selection rules on the RIXS intensities. Finally, our results
      demonstrate that using an intermediate excitation energy between L3 and L2 edges
      allows measurement of the density of 3d excited states as a fingerprint of the
      metal local structure. This opens up a new direction to pump-before-destroy
      investigations of transition metal complex structures and reaction mechanisms.

PMID- 29660294
TI  - High-Performance All-Polymer Solar Cells Achieved by Fused Perylenediimide-Based
      Conjugated Polymer Acceptors.
AB  - We report three n-type polymeric electron acceptors (PFPDI-TT, PFPDI-T, and PFPDI
      Se) based on the fused perylene diimide (FPDI) and thieno[3,2- b]thiophene,
      thiophene, or selenophene units for all-polymer solar cells (all-PSCs). These
      FPDI-based polymer acceptors exhibit strong absorption between 350 and 650 nm
      with wide optical bandgap of 1.86-1.91 eV, showing good absorption compensation
      with the narrow bandgap polymer donor. The lowest unoccupied molecular orbital
      (LUMO) energy levels were located at around -4.11 eV, which are comparable with
      those of the fullerene derivatives and other small molecular electron acceptors.
      The conventional all-PSCs based on the three polymer acceptors and PTB7-Th as
      polymer donor gave remarkable power conversion efficiencies (PCEs) of >6%, and
      the PFPDI-Se-based all-PSC achieved the highest PCE of 6.58% with a short-circuit
      current density ( Jsc) of 13.96 mA/cm2, an open-circuit voltage ( Voc) of 0.76 V,
      and a fill factor (FF) of 62.0%. More interestingly, our results indicate that
      the photovoltaic performances of the FPDI-based polymer acceptors are mainly
      determined by the FPDI unit with a small effect from the comonomers, which is
      quite different from the others reported rylenediimide-based polymer acceptors.
      This intriguing phenomenon is speculated as the huge geometry configuration of
      the FPDI unit, which minimizes the effect of the comonomer. These results
      highlight a promising future for the application of the FPDI-based polymer
      acceptors in the highly efficient all-PSCs.

PMID- 29660295
TI  - Breastfeeding Twins: Factors Related to Weaning.
AB  - BACKGROUND: Many factors may influence a woman's decision to start and maintain
      breastfeeding. Research aim: This study aimed to investigate the factors
      associated with breastfeeding cessation in twin infants during the first 6 months
      after birth and to describe the main reasons for weaning cited by mothers of
      twins. METHODS: This is a secondary data analysis of a prospective randomized
      trial conducted in Brazil. Data were obtained through longitudinal quantitative
      and qualitative self-reported interviews. One hundred twenty-eight women pregnant
      with twins and their 256 infants were followed for up to approximately 6 months,
      during which time breastfeeding data were obtained through face-to-face
      interviews at three different points after birth: 30 to 40 days (Time 1), 90 days
      (Time 2), and 180 days (Time 3). The association between weaning and the
      investigated factors was examined using survival analysis methodologies. RESULTS:
      Nonexclusive breastfeeding ( p = .004, Cox proportional hazards regression
      model), a lack of support during the lactation period ( p = .001), difficulty
      breastfeeding ( p = .003), a breastfeeding duration shorter than 12 months in a
      previous pregnancy ( p = .001), and infants' birth weight less than 2,300 g ( p <
      .001) were the factors associated with breastfeeding cessation. The main reasons
      for weaning cited by mothers of twins were insufficient human milk supply,
      infants' behavior, and returning to work. CONCLUSION: We have identified the
      factors associated with weaning in twin infants during the first 180 days of
      life. This knowledge can help improve strategies to increase breastfeeding rates
      in twins.

PMID- 29660296
TI  - Influence of AIDS antiretroviral therapy on the growth pattern.
AB  - OBJECTIVES: Human immunodeficiency virus infection can result in the early
      impairment of anthropometric indicators in children and adolescents. However,
      combined antiretroviral therapy has improved, in addition to the immune response
      and viral infection, the weight and height development in infected individuals.
      Therefore, the objective was to evaluate the effect of combined antiretroviral on
      the growth development of human immunodeficiency virus infected children and
      adolescents. SOURCE OF DATA: A systematic review was performed. In the study, the
      PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses)
      strategy was used as the eligibility criterion. The MEDLINE-PubMed and LILACS
      databases were searched using these descriptors: HIV, children, growth,
      antiretroviral therapy. The objective was defined by the population,
      intervention, comparison/control, and outcome (PICO) technique. Inclusion and
      exclusion criteria were applied for study selection. SYNTHESIS OF DATA: Of the
      549 studies indexed in MEDLINE-PubMed and LILACS, 73 were read in full, and 44
      were included in the review (33 showed a positive impact of combined
      antiretroviral therapy on weight/height development, ten on weight gain, and one
      on height gain in children and adolescents infected with human immunodeficiency
      virus). However, the increase in growth was not enough to normalize the height of
      infected children when compared to children of the same age and gender without
      human immunodeficiency virus infection. CONCLUSIONS: Combined antiretroviral
      therapy, which is known to play a role in the improvement of viral and
      immunological markers, may influence in the weight and height development in
      children infected with human immunodeficiency virus. The earlier the infection
      diagnosis and, concomitantly, of malnutrition and the start of combined
      antiretroviral therapy, the lower the growth impairment when compared to healthy
      children.

PMID- 29660297
TI  - Structured integration of family planning curriculum: comparative assessment of
      knowledge and skills among new medical graduates in Ethiopia.
AB  - OBJECTIVE: The objective was to assess if structured integration of a
      comprehensive family planning (FP) training into a medical school curriculum
      improves FP knowledge and skill scores of medical interns. STUDY DESIGN: We
      compared mean contraception knowledge scores of interns in a medical school with
      the integrated FP curriculum [intervention school] (n=56) to interns at four
      conventional medical curriculum schools without structured reinforcement of FP
      content [control schools] (n=161) in Ethiopia. A survey with 19 multiple choice
      contraception questions was administered. We also compared the mean contraception
      skills scores of the two groups at four Objective Structured Clinical Examination
      stations. The survey included self-reported number of contraception procedures
      and self-assessed competencies on a Likert scale. RESULTS: A total of 217 interns
      who have completed an Obstetrics and Gynecology rotation participated in the
      study. Interns from the intervention school reported performing substantially
      higher numbers of contraception procedures and rated themselves as being
      competent/highly competent across all procedures compared to the control schools
      (p<.001 for both). The mean knowledge score was significantly higher in the
      intervention school [13.1 vs. 8.7, difference 4.5, 95% CI: (3.7-5.2), p<.001].
      The mean contraceptive implant insertion skill score was twofold higher for
      interns in the intervention school [22 points vs. 11, difference 10.7, 95% CI:
      (8.6-12.8), p<.001 out of a maximum possible point of 30]. Statistically
      significant differences in skill scores were also observed for intrauterine
      device IUD insertion [15 vs. 12, p<.01] and implant removal [11 vs. 9, p=.01].
      CONCLUSION: A structured integration of family planning curriculum was associated
      with higher scores in knowledge, clinical skills and self-assessed competencies.
      IMPLICATIONS: Integrating comprehensive family planning training in medical
      curriculum can lead to graduating physicians who are more competent to offer the
      full range of FP options.

PMID- 29660298
TI  - Postpartum hemorrhage: new insights for definition and diagnosis.
AB  - The current definition of is inadequate for early recognition of this important
      cause of maternal death that is responsible for >80,000 deaths worldwide in 2015.
      A stronger definition of postpartum hemorrhage should include both blood loss and
      clinical signs of cardiovascular changes after delivery, which would help
      providers to identify postpartum hemorrhage more promptly and accurately. Along
      with the amount of blood loss, clinical signs, and specifically the shock index
      (heart rate divided by systolic blood pressure) appear to aid in more accurate
      diagnosis of postpartum hemorrhage.

PMID- 29660301
TI  - Prevalence Estimates for Hidradenitis Suppurativa among Children and Adolescents
      in the United States: A Gender- and Age-Adjusted Population Analysis.
AB  - The prevalence of hidradenitis suppurativa (HS) in the pediatric population is
      unknown. We sought to establish standardized overall as well as gender-, age-,
      and race-specific prevalence estimates of HS among children and adolescents in
      the United States. We performed a cross-sectional analysis in a heterogeneous
      sample of 55 million patients across all census regions. We identified 1,240
      patients with HS in whom the ratio of girls to boys was 3.8:1. Almost all (96.8%)
      patients with HS were >=10 years of age. Overall, HS prevalence was 0.028%, or
      28.1 (95% confidence interval [CI] 26.5-29.7) per 100,000 children and
      adolescents. Standardized prevalence was higher in girls (44.6 [95% CI 41.8-47.5]
      per 100,000), in patients aged 15-17 years (113.7 [95% CI 106.4-121.4] per
      100,000), and among African Americans (78.7 [95% CI 71.0-86.9] per 100,000).
      Highest prevalence of HS was observed among female adolescents aged 15-17 years
      who were African Americans (525.1 [95% CI 459.4-597.5] per 100,000) and biracial
      (253.2 [95% CI 121.4-465.6] per 100,000). Patients with HS who went undiagnosed
      were not captured, and as such prevalence estimates may be underestimated. HS
      appears to be a postpubertal disease that disproportionately afflicts girls and
      African Americans in the pediatric population.

PMID- 29660300
TI  - The Major Orphan Forms of Ichthyosis Are Characterized by Systemic T-Cell
      Activation and Th-17/Tc-17/Th-22/Tc-22 Polarization in Blood.
AB  - The ichthyoses are rare skin disorders with immune and barrier aberrations.
      Identifying blood phenotypes may advance targeted therapeutics. We aimed to
      compare frequencies of skin homing/cutaneous lymphocyte antigen (+) versus
      systemic/cutaneous lymphocyte antigen (-) "polar" CD4+/CD8+ and activated T-cell
      subsets in ichthyosis versus atopic dermatitis, psoriasis, and control blood,
      with appropriate clinical correlations. Flow cytometry was used to measure IFN
      gamma, IL-13, IL-9, IL-17, and IL-22 cytokines in CD4+/CD8+ T cells, with
      inducible co-stimulator molecule and HLA-DR defining mid- and long-term T-cell
      activation, respectively. We compared peripheral blood from 47 patients with
      ichthyosis (congenital ichthyosiform erythroderma, lamellar ichthyosis,
      epidermolytic ichthyosis, and Netherton syndrome) with 43 patients with atopic
      dermatitis and 24 patients with psoriasis and 59 age-matched controls. Clinical
      measures included the ichthyosis severity score, with subsets for erythema and
      scaling, transepidermal water loss, and pruritus. All ichthyoses had excessive
      inducible co-stimulator molecule activation (P < 0.001), particularly
      epidermolytic ichthyosis. Significantly elevated IL-17- (P < 0.05) and IL-22
      producing (P < 0.01) T cells characterized ichthyoses, mainly Netherton syndrome
      and congenital ichthyosiform erythroderma (P < 0.05). Increased T helper
      2/cytotoxic T cell 2/T helper 9 (P < 0.05) and similar IFN-gamma frequencies (P >
      0.1) versus controls were also noted. IL-17/IL-22-producing cells clustered with
      clinical measures, whereas IFN-gamma clustered with age. Our data show peripheral
      blood IL-17/IL-22 activation across the ichthyoses, correlating with clinical
      measures. Targeted therapies should dissect the relative contribution of polar
      cytokines to disease pathogenesis.

PMID- 29660299
TI  - Infection-induced thrombin production: a potential novel mechanism for preterm
      premature rupture of membranes (PPROM).
AB  - BACKGROUND: Preterm premature rupture of membranes is a leading contributor to
      maternal and neonatal morbidity and death. Epidemiologic and experimental studies
      have demonstrated that thrombin causes fetal membrane weakening and subsequently
      preterm premature rupture of membranes. Although blood is suspected to be the
      likely source of thrombin in fetal membranes and amniotic fluid of patients with
      preterm premature rupture of membranes, this has not been proved. Ureaplasma
      parvum is emerging as a pathogen involved in prematurity, which includes preterm
      premature rupture of membranes; however, until now, prothrombin production that
      has been induced directly by bacteria in fetal membranes has not been described.
      OBJECTIVE: This study was designed to investigate whether Ureaplasma parvum
      exposure can induce prothrombin production in fetal membranes cells. STUDY
      DESIGN: Primary fetal membrane cells (amnion epithelial, chorion trophoblast, and
      decidua stromal) or full-thickness fetal membrane tissue explants from elective,
      term, uncomplicated cesarean deliveries were harvested. Cells or tissue explants
      were infected with live Ureaplasma parvum (1*105, 1*106 or 1*107 colony-forming
      units per milliliter) or lipopolysaccharide (Escherichia coli J5, L-5014; Sigma
      Chemical Company, St. Louis, MO; 100 ng/mL or 1000 ng/mL) for 24 hours. Tissue
      explants were fixed for immunohistochemistry staining of thrombin/prothrombin.
      Fetal membrane cells were fixed for confocal immunofluorescent staining of the
      biomarkers of fetal membrane cell types and thrombin/prothrombin. Protein and
      messenger RNA were harvested from the cells and tissue explants for Western blot
      or quantitative reverse transcription polymerase chain reaction to quantify
      thrombin/prothrombin protein or messenger RNA production, respectively. Data are
      presented as mean values +/- standard errors of mean. Data were analyzed using 1
      way analysis of variance with post hoc Dunnett's test. RESULTS: Prothrombin
      production and localization were confirmed by Western blot and immunostainings in
      all primary fetal membrane cells and tissue explants. Immunofluorescence
      observations revealed a perinuclear localization of prothrombin in amnion
      epithelial cells. Localization of prothrombin in chorion and decidua cells was
      perinuclear and cytoplasmic. Prothrombin messenger RNA and protein expression in
      fetal membranes were increased significantly by Ureaplasma parvum, but not
      lipopolysaccharide, treatments in a dose-dependent manner. Specifically,
      Ureaplasma parvum at a dose of 1*107 colony-forming units/mL significantly
      increased both prothrombin messenger RNA (fold changes in amnion: 4.1+/-1.9;
      chorion: 5.7+/-4.2; decidua: 10.0+/-5.4; fetal membrane: 9.2+/-3.0) and protein
      expression (fold changes in amnion: 138.0+/-44.0; chorion: 139.6+/-15.1; decidua:
      56.9+/-29.1; fetal membrane: 133.1+/-40.0) compared with untreated control
      subjects. Ureaplasma parvum at a dose of 1*106 colony-forming units/mL
      significantly up-regulated prothrombin protein expression in chorion cells (fold
      change: 54.9+/-5.3) and prothrombin messenger RNA expression in decidua cells
      (fold change: 4.4+/-1.9). CONCLUSION: Our results demonstrate that prothrombin
      can be produced directly by fetal membrane amnion, chorion, and decidua cells.
      Further, prothrombin production can be stimulated by Ureaplasma parvum exposure
      in fetal membranes. These findings represent a potential novel underlying
      mechanism of Ureaplasma parvum-induced rupture of fetal membranes.

PMID- 29660302
TI  - miR-223-RhoB signaling pathway regulates the proliferation and apoptosis of colon
      adenocarcinoma.
AB  - MicroRNAs (miRNAs) can function as tumor suppressor or oncogenic genes. The
      putative targets of miR-223 include tumor suppressor gene, RhoB. Here we sought
      to investigate the role of miR-223-RhoB signaling pathway in proliferation of
      colon cancer. We used Western blot, immunofluorescence staining, or RT-PCR to
      detect expression levels of miR-223 and RhoB in colon adenocarcinoma and adjacent
      non-cancerous tissue samples, or in human colon adenocarcinoma cell lines. MTT
      assay was used to determine proliferation and apoptosis in cell lines. We further
      used Western blot to determine levels of cell cycle regulators CDK1 and Cyclin B1
      with anti-miR-223 or apoptosis with overexpression of RhoB. The expression level
      of miR-223 was significantly upregulated in clinical samples and cell lines of
      colon adenocarcinoma, in contrast to down-regulation of RhoB. In addition, we
      showed that inhibition of miR-223 led to upregulation of RhoB and in turn
      suppression of proliferation of colon adenocarcinoma. Moreover, inhibition of miR
      223 or overexpression of RhoB induced cell arrest or apoptosis in colon
      adenocarcinoma. These results suggest that miR-223-RhoB signaling pathway plays
      an important role in modulation of proliferation, cell arrest, and apoptosis in
      colon cancer.

PMID- 29660303
TI  - Potential role of MicroRNA 200c gene expression in assessment of colorectal
      cancer.
AB  - BACKGROUND AND AIM: Colorectal cancer (CRC) is a common cancer worldwide that
      affects men and women of all racial and ethnic groups. Recent evidence supports
      the role of microRNAs in CRC. We planned to investigate microRNA200c expression
      and its relation with diagnosis, prognosis, metastasis and overall survival in
      CRC patients. This study enrolled 90 subjects (3'0 CRC patients, 30 patients with
      benign colorectal polyps and 30 healthy control subjects). METHODS: Laboratory
      investigations included measurement of serum CA19-9 and CEA by enzyme linked
      immunosorbent assay (ELISA) method and relative quantitation (RQ) of microRNA200c
      gene expression by real time PCR technique. RESULTS: Significant higher
      MicroRNA200c expression levels in CRC patients versus both benign (P < 0.011) and
      control groups (P < 0.001), additionally, benign group had elevated levels versus
      control (P < 0.001). MicroRNA 200c at cutoff >4.56 had sensitivity 86.67% and
      specificity 73.33% (P < 0.001) for CRC discrimination. Kaplan-Meier survival
      analysis revealed significant association (P = 0.028) of high expression of
      microRNA200c with decreased overall survival. CONCLUSION: Noticeable up
      regulation of microRNA200c in CRC and its remarkable relation with unfavorable
      survival suggesting its potential dual use as a diagnostic and prognostic
      biomarker for CRC.

PMID- 29660304
TI  - Circadian rhythm resynchronization improved isoflurane-induced cognitive
      dysfunction in aged mice.
AB  - Postoperative cognitive dysfunction (POCD) is a common clinical phenomenon
      characterized by cognitive deficits in patients after anesthesia and surgery.
      Advanced age is a significant independent risk factor for POCD. We previously
      reported that in young mice, sleep-wake rhythm is involved in the isoflurane
      induced memory impairment. In present study, we sought to determine whether
      advanced age increased the risk of POCD through aggravated and prolonged post
      anesthetic circadian disruption in the elderly. We constructed POCD model by
      submitting the mice to 5-h 1.3% isoflurane anesthesia from Zeitgeber Time (ZT) 14
      to ZT19. Under novel object recognition assay (NOR) and Morris water maze (MWM)
      test, We found 5-h isoflurane anesthesia impaired the cognition of young mice for
      early 3 days after anesthesia but damaged the aged for at least 1 week. With Mini
      Mitter continuously monitoring, a 3.22 +/- 0.75 h gross motor activity acrophase
      delay was manifested in young mice on D1, while in the aged mice, the gross motor
      activity phase shift lasted for 3 days, consistent with the body temperature
      rhythm trends of change. Melatonin has been considered as an effective remedy for
      circadian rhythm shift. In aged mice, melatonin was pretreated intragastrically
      at the dose of 10 mg/kg daily for 7 consecutive days before anesthesia. We found
      that melatonin prevented isoflurane-induced cognitive impairments by restoring
      the locomotor activity and temperature circadian rhythm via clock gene
      resynchronization. Overall, these results indicated that Long-term isoflurane
      anesthesia induced more aggravated and prolonged memory deficits and circadian
      rhythms disruption in aged mice. Melatonin could prevent isoflurane-induced
      cognitive impairments by circadian rhythm resynchronization.

PMID- 29660305
TI  - Temporomandibular Joint Reconstruction in Patients With Autoimmune/Connective
      Tissue Disease.
AB  - PURPOSE: To evaluate clinical outcomes in patients with autoimmune or connective
      tissue (CT) disease undergoing temporomandibular joint (TMJ) reconstruction.
      MATERIALS AND METHODS: Patients were divided into 2 groups based on type of TMJ
      reconstruction. Patients in group 1 (n = 9) underwent autogenous reconstruction
      and had a diagnosis of rheumatoid arthritis (5), lupus arthritis (1), and
      psoriatic arthritis (3). Patients in group 2 (n = 2l) had alloplastic
      reconstruction with a patient-fitted total joint prosthesis (TMJ Concepts,
      Ventura, CA) and had a diagnosis of rheumatoid arthritis (15), lupus (3), and
      psoriatic arthritis (3). Standardized clinical and radiographic examinations were
      performed before surgery, immediately after surgery, and at longest follow-up
      after surgery (T3). RESULTS: Group l showed no meaningful improvement in maximal
      opening without pain, a decrease in lateral excursions, minimal decrease in TMJ
      pain, and a 32% relapse of chin projection at point B at T3. Average postsurgery
      follow-up time was 58 months. Postsurgical ankylosis was seen in 22% of patients.
      In contrast, group 2 showed a statistically meaningful decrease in subjective TMJ
      pain and lateral excursive movements and improvement in jaw function, diet,
      maximal incisal opening without pain, and only 5% showed a relapse at point B at
      T3. Average postsurgical follow-up in this group was 78 months. CONCLUSIONS:
      Improved treatment outcomes were obtained with alloplastic TMJ total joint
      reconstruction compared with autogenous TMJ reconstruction in patients with
      autoimmune or CT disease.

PMID- 29660306
TI  - Ablation of toll-like receptor 4 attenuates aging-induced myocardial remodeling
      and contractile dysfunction through NCoRI-HDAC1-mediated regulation of autophagy.
AB  - Aging is usually accompanied with overt structural and functional changes as well
      as suppressed autophagy in the heart although the precise regulatory mechanisms
      are somewhat unknown. Here we evaluated the role of the innate proinflammatory
      mediator toll-like receptor 4 (TLR4) in cardiac aging and the underlying
      mechanism with a focus on autophagy. Cardiac geometry and function were monitored
      in young or old wild-type (WT) and TLR4 knockout (TLR4-/-) mice using
      echocardiography, IonOptix(r) edge-detection and fura-2 techniques. Levels of
      autophagy and mitophagy, nuclear receptor corepressor 1 (NCoR1) and histone
      deacetylase I (HDAC1) were examined using western blot. Transmission electronic
      microscopy (TEM) was employed to monitor myocardial ultrastructure. Our results
      revealed that TLR4 ablation alleviated advanced aging (24 months)-induced changes
      in myocardial remodeling (increased heart weight, chamber size, cardiomyocyte
      cross-sectional area), contractile function and intracellular Ca2+ handling as
      well as autophagy and mitophagy [Beclin-1, Atg5, LC3B, PTEN-induced putative
      kinase 1 (PINK1), Parkin and p62]. Aging downregulated levels of NCoR1 and HDAC1
      as well as their interaction, the effects were significantly attenuated or
      negated by TLR4 ablation. Advanced aging disturbed myocardial ultrastructure as
      evidenced by loss of myofilament alignment and swollen mitochondria, which was
      obliterated by TLR4 ablation. Moreover, aging suppressed autophagy (GFP-LC3B
      puncta) in neonatal mouse cardiomyocytes, the effect of which was negated by the
      TLR4 inhibitor CLI-095. Inhibition of HDCA1 using apicidin cancelled off CLI095
      induced beneficial response of GFP-LC3B puncta against aging. Our data
      collectively indicate a role for TLR4-mediated autophagy in cardiac remodeling
      and contractile dysfunction in aging through a HDAC1-NCoR1-dependent mechanism.

PMID- 29660307
TI  - Gonadotropin receptors of Labeo rohita: Cloning and characterization of full
      length cDNAs and their expression analysis during annual reproductive cycle.
AB  - Follicle-stimulating hormone (Fsh) and luteinizing hormone (Lh), secreted from
      pituitary, stimulate gonadal function by binding to their cognate receptors FSH
      receptor (FSHR), and LH/choriogonadotropin receptor (LHCGR). Rohu (Labeo rohita)
      is a commercially important seasonal breeder freshwater fish species, but till
      date, the regulation of expression of gonadotropins and their receptors gene
      during different phases of annual reproductive cycle has not been investigated.
      We envisaged the critical role of these molecules during seasonal gonadal
      development in this carp species. We cloned full- length cDNAs of fshra and
      lhcgrba from rohu testis using RACE (Rapid amplification of cDNA ends) and
      analyzed their expression along with fsh and lh by quantitative real time PCR
      (qRT-PCR) assay at various gonadal developmental stages of the annual
      reproductive cycle. Full-length rohu fshra and lhcgrba cDNA encodes 670 and 716
      amino acids respectively, and in adult fish, they were widely expressed in brain,
      pituitary, gonad, liver, kidney, head kidney, heart, muscle, gill, fin, eye and
      intestine. In male, both fsh and fshra transcripts showed high level of
      expression during spermatogenesis, however, in female, expression level was found
      to be higher in the fully grown oocyte stages. The expression of rohu lh and
      lhcgrba mRNA increased with increment of gonadosomatic index and showed highest
      level during spermiation stage in male and fully matured oocyte stage in female.
      These results together may suggest the involvement of fshra and lhcgrba in
      regulating function of seasonal gonadal development in rohu.

PMID- 29660308
TI  - The effects of replacing eggs with chicks on mesotocin, dopamine, and prolactin
      in the native Thai hen.
AB  - The mesotocinergic (MTergic) and dopaminergic (DAergic) systems have been
      documented to play pivotal roles in maternal behaviors in native Thai chickens.
      In native Thai chickens, plasma prolactin (PRL) concentrations are associated
      with maternal behaviors, which are also controlled by the DAergic system.
      However, the role of MT in conjunction with the roles of DA and PRL on the
      neuroendocrine regulation of the transition from incubating to rearing behavior
      has never been studied. Therefore, the aim of this study was to investigate the
      association of MT, DA, and PRL during the transition from incubating to rearing
      behavior in native Thai hens. Using an immunohistochemistry technique, the
      numbers of MT-immunoreactive (-ir) and tyrosine hydroxylase-ir (TH-ir, a DA
      marker) neurons were compared between incubating hens (INC; n = 6) and hens for
      which the incubated eggs were replaced with 3 newly hatched chicks for 3 days
      after 6, 10, and 14 days of incubation (REC; n = 6). Plasma PRL concentrations
      were determined by enzyme-linked immunosorbent assay. The results revealed that
      the numbers of MT-ir neurons within the nucleus supraopticus, pars ventralis
      (SOv), nucleus preopticus medialis (POM), and nucleus paraventricularis
      magnocellularis (PVN) increased in the REC hens when compared with those of the
      INC hens at 3 different time points (at days 9, 13, and 17). On the other hand,
      the number of TH-ir neurons in the nucleus intramedialis (nI) decreased in the
      REC13 and REC17 hens when compared with those of the INC hens. However, the
      number of TH-ir neurons in the nucleus mamillaris lateralis (ML) only decreased
      in the REC13 hens when compared with the INC13 hens. The decrease in the numbers
      of TH-ir neurons within the nI and ML is associated with the decrease in the
      levels of plasma PRL. This study suggests that the presence of either eggs or
      chicks is the key factor regulating the MTergic system within the SOv, POM, and
      PVN and the DAergic system within the nI and ML during the transition from
      incubating to rearing behavior in native Thai chickens. The results further
      indicate that these two systems play pivotal roles in the transition from
      incubating to rearing behavior in this equatorial species.

PMID- 29660309
TI  - Alterations of pigment composition and their interactions in response to
      different light conditions in the diatom Chaetoceros gracilis probed by time
      resolved fluorescence spectroscopy.
AB  - Maintenance of energy balance under changeable light conditions is an essential
      function of photosynthetic organisms to achieve efficient photochemical
      reactions. Among the photosynthetic organisms, diatoms possess light-harvesting
      fucoxanthin chlorophyll (Chl) a/c-binding protein (FCP) as peripheral antennas.
      However, how diatoms regulate excitation-energy distribution between FCP and the
      two photosystem cores during light adaptation is poorly understood. In this
      study, we examined spectroscopic properties of a marine diatom Chaetoceros
      gracilis adapted in the dark and at photosynthetic photon flux density at 30 and
      300 MUmol photons m-2 s-1. Absorption spectra at 77 K showed significant changes
      in the Soret region, and 77-K steady-state fluorescence spectra showed
      significant differences in the spectral shape and relative fluorescence intensity
      originating from both PSII and PSI, among the cells grown under different light
      conditions. These results suggest alterations of pigment composition and their
      interactions under the different light conditions. These alterations affected the
      excitation-energy dynamics monitored by picosecond time-resolved fluorescence
      analyses at 77 K significantly. The contributions of Chls having lower energy
      levels than the reaction center Chls in the two photosystems to the energy
      dynamics were clearly identified in the three cells but with presumably different
      roles. These findings provide insights into the regulatory mechanism of
      excitation-energy balance in diatoms under various light conditions.

PMID- 29660310
TI  - A modeling and simulation perspective on the mechanism and function of
      respiratory complex I.
AB  - Respiratory complex I is a giant redox-driven proton pump, and central to energy
      production in mitochondria and bacteria. It catalyses the reduction of quinone to
      quinol, and converts the free energy released into the endergonic proton
      translocation across the membrane. The proton pumping sets up the proton
      electrochemical gradient, which propels the synthesis of ATP. Despite the
      availability of extensive biochemical, biophysical and structural data on complex
      I, the mechanism of coupling between the electron and proton transfer reactions
      remain uncertain. In this work, we discuss current state-of-the-art in the field
      with particular emphasis on the molecular mechanism of respiratory complex I, as
      deduced from computational modeling and simulation approaches, but in strong
      alliance with the experimental data. This leads to novel synthesis of mechanistic
      ideas on a highly complex enzyme of the electron transport chain that has been
      associated with a number of mitochondrial and neurodegenerative disorders.

PMID- 29660311
TI  - Prevalence and genotypes of Enterocytozoon bieneusi in China.
AB  - Enterocytozoon bieneusi has been considered as the most frequently diagnosed
      microsporidian species in humans and various animal species, accounting for more
      than 90% of the cases of human microsporidiosis. Spores of this pathogen excreted
      from both symptomatic and asymptomatic hosts into environment also would be an
      important source of waterborne outbreak of microsporidiosis. Due to limited
      effective drugs available but with too much side effects to mammals (eg. toxic),
      accurate characterization of E. bieneusi in both humans and animals is essential
      to implement effective control strategies to this pathogen. In China, E. bieneusi
      infection was presented in humans and some animals with high prevalence. Analysis
      of genetic variations of the internal transcribed spacer (ITS) sequences found
      361 genotypes in China, and some novel genotypes were identified in some specific
      hosts. Additionally, associations between infections and some risk factors were
      also observed. In the present article, we reviewed the current status of
      prevalence, genotypes, multilocus genotypes (MLGs) in humans, various animals and
      waters in China. These findings will provide basic information for developing
      effective control strategies against E. bieneusi infection in China as well as
      other countries.

PMID- 29660312
TI  - The EGF/Ras pathway controls growth in Drosophila via ribosomal RNA synthesis.
AB  - The Ras small G-protein is a conserved regulator of cell and tissue growth during
      animal development. Studies in Drosophila have shown how Ras can stimulate a RAF
      MEK-ERK signalling pathway to control cell growth and proliferation in response
      to Epidermal Growth Factor (EGF) stimulation. This work has also defined several
      transcription factors that can function as downstream growth effectors of the
      EGF/Ras/ERK pathway by stimulating mRNA transcription. Here we report on
      stimulation of RNA polymerase I (Pol I)-mediated ribosomal RNA (rRNA) synthesis
      as a growth effector of Ras/ERK signalling in Drosophila. We show that Ras/ERK
      signalling promotes an increase in nucleolar size in larval wing discs, which is
      indicative of increased ribosome synthesis. We also find that activation of
      Ras/ERK signalling promotes rRNA synthesis both in vivo and in cultured
      Drosophila S2 cells. We show that Ras signalling can regulate the expression of
      the Pol I transcription factor TIF-IA, and that this regulation requires dMyc.
      Finally, we find that TIF-IA-mediated rRNA synthesis is required for Ras/ERK
      signalling to drive proliferation in both larval and adult Drosophila tissues.
      These findings indicate that Ras signalling can promote ribosome synthesis in
      Drosophila, and that this is one mechanism that contributes to the growth effects
      of the Ras signalling pathway.

PMID- 29660314
TI  - Nrf2 as a therapeutic target for rheumatic diseases.
AB  - Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a master regulator of
      cellular protective processes. Rheumatic diseases are chronic conditions
      characterized by inflammation, pain, tissue damage and limitations in function.
      Main examples are rheumatoid arthritis, systemic lupus erythematosus,
      osteoarthritis and osteoporosis. Their high prevalence constitutes a major health
      problem with an important social and economic impact. A wide range of evidence
      indicates that Nrf2 may control different mechanisms involved in the
      physiopathology of rheumatic conditions. Therefore, the appropriate expression
      and balance of Nrf2 is necessary for regulation of oxidative stress,
      inflammation, immune responses, and cartilage and bone metabolism. Numerous
      studies have demonstrated that Nrf2 deficiency aggravates the disease in
      experimental models while Nrf2 activation results in immunoregulatory and anti
      inflammatory effects. These reports reinforce the increasing interest in the
      pharmacologic regulation of Nrf2 and its potential applications. Nevertheless, a
      majority of Nrf2 inducers are electrophilic molecules which may present off
      target effects. In recent years, novel strategies have been sought to modulate
      the Nrf2 pathway which has emerged as a therapeutic target in rheumatic
      conditions.

PMID- 29660313
TI  - The convergent roles of CD271/p75 in neural crest-derived melanoma plasticity.
AB  - The embryonic microenvironment is an important source of signals that promote
      multipotent cells to adopt a specific fate and direct cells along distinct
      migratory pathways. Yet, the ability of the embryonic microenvironment to retain
      multipotent progenitors or reprogram de-differentiated cells is less clear.
      Mistakes in cell differentiation or migration often result in developmental
      defects and tumorigenesis, including aggressive cancers that share many
      characteristics with embryonic progenitor cells. This is a striking feature of
      the vertebrate neural crest, a multipotent and highly migratory cell population
      first identified by His (1868) with the potential to metamorphose into aggressive
      melanoma cancer. In this perspective, we address the roles of CD271/p75 in tumor
      initiation, phenotype switching and reprogramming of metastatic melanoma and
      discuss the convergence of these roles in melanoma plasticity.

PMID- 29660315
TI  - Metronomic vinorelbine is directly active on Non Small Cell Lung Cancer cells and
      sensitizes the EGFRL858R/T790M cells to reversible EGFR tyrosine kinase
      inhibitors.
AB  - Metronomic vinorelbine (mVNR) has been described primarily as an antiangiogenic
      therapy, and no direct effects of mVNR on Non Small Cell Lung Cancer (NSCLC)
      cells has yet been demonstrated. The aims of this study were i) to establish the
      direct activity of mVNR on NSCLC cells either EGFR wt or EGFRL858R/T790M, and ii)
      to quantify the synergism of the combination with reversible EGFR tyrosine kinase
      inhibitors (TKIs), investigating the underlying mechanism of action.
      Proliferation assays were performed on A-549 (wt EGFRhigh), H-292 (EGFR-wt), H
      358 (EGFR-wt), H-1975 (EGFRL858R/T790M) NSCLC cell lines exposed to mVNR, its
      active metabolite deacetyl-VNR (D-VNR), gefitinib and erlotinib for 144 h
      treatments. The synergism between mVNR and EGFR TKIs was determined by the
      combination index (CI) in EGFR-wt and H-1975 NSCLC cells. Cyclin-D1 and ABCG2
      genes expression and protein levels were measured by RT-PCR and ELISA assays, as
      well as the phosphorylation of ERK1/2 and Akt. Intracellular concentrations of
      EGFR TKIs and VNR were investigated with a mass spectrometry system. mVNR, and
      its active metabolite D-VNR, were extremely active on NSCLC cells, in particular
      on H-1975 (IC50 = 13.56 +/- 2.77 pM), resistant to TKIs. mVNR inhibited the
      phosphorylation of ERK1/2 and Akt and significantly decreased the expression of
      both cyclin-D1 and ABCG2 m-RNA and protein. The simultaneous combination of VNR
      and reversible EGFR TKIs showed a strong synergism on EGFR-wt NSCLC cells and on
      H-1975 cells (e.g. CI = 0.501 for 50% of affected cells), increasing the
      intracellular concentrations of EGFR TKIs (e.g. +50.5% vs. gefitinib alone). In
      conclusions, mVNR has direct effects on NSCLC cells and sensitizes resistant
      cells to EGFR TKIs, increasing their intracellular concentrations.

PMID- 29660316
TI  - Vitrification tendency and stability of DP6-based vitrification solutions for
      complex tissue cryopreservation.
AB  - Vitrification tendency and stability of the amorphous state were analyzed by
      means of differential scanning calorimetry (DSC) for the vitrification solution
      DP6, with and without additional solutes to enhance ice suppression. This study
      is a part of an ongoing research effort to characterize the thermophysical and
      mechanical properties of DP6 and its derivatives, and their qualities as
      cryoprotective solutions. DP6 was determined to have a critical cooling rate
      necessary to ensure vitrification of 2.7  degrees C/min. The following additional
      solutions were tested: DP6 + 6% (2R, 3R) 2,3-butanediol, DP6 + 6% 1,3
      cyclohexanediol, DP6 + 6% (0.175M) sucrose, DP6 + 12% PEG 400, and DP6 + 17.1%
      (0.5 M) sucrose. The additives decreased the critical cooling rate of the DP6
      solution to rates below 1  degrees C/min that were not quantifiable by the DSC
      techniques used. The following critical warming rates necessary to avoid
      devitrification were identified for DP6 and the modified solutions, respectively:
      189  degrees C/min, 5  degrees C/min, ~ 1  degrees C/min, 15  degrees C/min, <1 
      degrees C/min, and <1  degrees C/min. Glass transition temperatures and melting
      temperatures were also measured. Sucrose was the least effective additive on a
      per mass basis, with 1,3-cyclohexanediol appearing to be the most effective
      additive for suppressing ice formation in DP6.

PMID- 29660317
TI  - History of cryobiology, with special emphasis in evolution of mouse sperm
      cryopreservation.
AB  - Confucius said study the past if you would define the future and a popular
      statement says that history depends on who writes it. To talk about history it is
      necessary to find and define a milestone where to start the narration. The
      intention of this quick review is to take the reader through moments and selected
      publications; part and pieces of memories showing how the concept of
      cryopreservation, specifically for mouse sperm, was conceived and sustained as we
      know it today. Beginning with the development of the microscope (1677) and
      continuing through the 17th century with the first documented observation by L.
      Spallanzani describing that sperm could maintain the motility under cold
      conditions. As J. Sherman suggested, we divide the cryopreservation evolution
      into two sequences, previous to and after 1949 when Polge, Smith and Parkes
      discovered the property of glycerol as cryoprotectant. Later, in 1972, D.
      Whittingham, S. Leibo, and P. Mazur applying a slow freezing process achieved the
      first embryo freezing (mouse). During that time many theories were scientifically
      confirmed. Among those, Peter Mazur demonstrated the relation between the speed
      of freezing and intracellular ice formation, and Stanley Leibo that each cell
      type has their unique freezing curve. In 1950, after the discovery of the
      protective aspect of glycerol, sperm from many mammals were frozen, except from
      the mouse. It was in the early 90's when the mouse sperm freezing becomes
      important and it was a real challenge for many groups, nevertheless, the
      technique using skim milk and raffinose modified by Dr Nakagata was the beginning
      of a different story ....

PMID- 29660318
TI  - Reply by Authors.

PMID- 29660319
TI  - Editorial Comment.

PMID- 29660320
TI  - Water-pocket endoscopic submucosal dissection for superficial gastric neoplasms
      (with video).
AB  - BACKGROUND AND AIMS: During endoscopic submucosal dissection (ESD), a clear view
      is essential for precise dissection of the appropriate submucosal layer. Some
      advantages have been reported for underwater techniques of endoscopic resection
      in comparison with the gas insufflation method. We have developed a new ESD
      method with the creation of a local water pocket (WP) that provides a clear view
      in the dissection field. Therefore, we aimed to investigate the feasibility and
      safety of WP-ESD for superficial gastric neoplasms. METHODS: We prospectively
      recruited 50 patients with gastric neoplasms (early gastric cancer or gastric
      adenomas) between April 2017 and December 2017. Among them, 48 patients were
      treated with the WP-ESD technique. The patients undergoing WP-ESD were compared
      with 48 patients treated with standard ESD (S-ESD) who were selected by
      propensity score matching. The primary outcome was the ESD procedure time.
      RESULTS: Total procedure time was significantly shorter in the WP-ESD group than
      in the S-ESD group (median [interquartile range], 27.5 [19-45] minutes vs 41
      [29.8-69] minutes; P < .001). Similarly, the dissection speed was significantly
      greater in the WP-ESD group than in the S-ESD group (median [interquartile
      range], 22.5 [16.8-35.3] mm2/min vs 17.3 [12.7-22.1] mm2/min; P < .001). The
      rates of complete en bloc resection in the WP-ESD group and the S-ESD group were
      97.9% and 95.8%, respectively (P > .99). There were no perforations in either
      group. CONCLUSION: WP-ESD was associated with a shorter procedure time than S
      ESD. WP-ESD may provide an alternative method for resection of superficial
      gastric neoplasms. (Clinical trial registration number: UMIN 000030266.).

PMID- 29660321
TI  - Reliability among central readers in the evaluation of endoscopic disease
      activity in pouchitis.
AB  - BACKGROUND AND AIMS: Pouchitis is a common adverse event after proctocolectomy
      with ileal pouch anal anastomosis for ulcerative colitis. Evaluation of pouchitis
      disease activity and response to treatment requires use of validated indices. We
      assessed the reliability of items evaluating endoscopic pouchitis disease
      activity. METHODS: Twelve panelists used a modified RAND appropriateness
      methodology to rate the appropriateness of items evaluating endoscopic pouchitis
      disease activity derived from a systematic review and also identified additional
      potential endoscopic items based on expert opinion. Four central readers then
      evaluated 50 pouchoscopy videos in triplicate, in random order. Intra- and inter
      rater reliability for each item was assessed by calculating and comparing
      intraclass correlation coefficients (ICCs). A Delphi process identified common
      sources of disagreement among the readers. RESULTS: Ten existing endoscopic items
      were identified from the systematic review and an additional 7 exploratory items
      from the panelists. ICCs for inter-rater reliability were highest for the
      existing item of pouch ulceration (.72; 95% confidence interval [CI], .60-.82)
      and for the exploratory item of ulcerated surface in the pouch body (.67; 95% CI,
      .53-.75). Inter-rater reliability for all other existing and exploratory items
      was "moderate" (ICC < .60). The item "ulcerated surface in the pouch body"
      demonstrated the best correlation with a global evaluation of lesion severity (r
      = .80; 95% CI, .73-.85). CONCLUSION: Substantial reliability was observed only
      for the endoscopic items of ulceration and ulcerated surface in the pouch body.
      Future studies should assess responsiveness to treatment in the next stage toward
      development of an endoscopic pouchitis disease activity index.

PMID- 29660322
TI  - Efficacy and safety of endobiliary radiofrequency ablation for the eradication of
      residual neoplasia after endoscopic papillectomy: a multicenter prospective
      study.
AB  - BACKGROUND AND AIMS: Endobiliary dysplasia may persist after endoscopic
      papillectomy. Intraductal radiofrequency ablation (ID-RFA) is a potential
      alternative to complementary surgery. The aim of this study was to evaluate the
      efficacy and safety of ID-RFA for the treatment of adenomatous intraductal
      residue after endoscopic papillectomy. METHODS: A prospective open-label
      multicenter study included patients with histologically proven endobiliary
      adenoma remnant (ductal extent <20 mm) after endoscopic papillectomy for
      ampullary tumor. RFA (effect 8, power 10 W, 30 seconds) was performed during
      ERCP. Biliary +/- pancreatic stent was placed at the end of the procedure.
      Endpoints were (1) the rate of residual neoplasia (ie, low-grade dysplasia [LGD],
      high-grade dysplasia [HGD], or invasive carcinoma) at 6 and 12 months, (2) rate
      of surgery, and (3) adverse events. RESULTS: Twenty patients (67 +/- 11 years of
      age, 12 men) were included. The endobiliary adenoma was in LGD in 15 patients and
      HGD in 5 patients. All underwent 1 successful ID-RFA session with biliary stent
      placement and recovered uneventfully. Five (25%) received a pancreatic stent. The
      rates of residual neoplasia were 15% and 30% at 6 and 12 months, respectively.
      Only 2 patients (10%) were referred for surgery. Eight patients (40%) experienced
      at least 1 adverse event between ID-RFA and 12 months of follow-up. No major
      adverse event occurred. HGD at inclusion was associated with higher dysplasia
      recurrence at 12 months (P = .01). CONCLUSIONS: ID-RFA of residual endobiliary
      dysplasia after endoscopic papillectomy can be offered as an alternative to
      surgery, with a 70% chance of dysplasia eradication at 12 months after a single
      session and a good safety profile. Patient follow-up remains warranted after ID
      RFA. (Clinical trial registration number: NCT02825524.).

PMID- 29660323
TI  - Nationwide Trends in Acute and Chronic Pancreatitis Among Privately Insured
      Children and Non-Elderly Adults in the United States, 2007-2014.
AB  - BACKGROUND & AIMS: Epidemiologic analyses of acute pancreatitis (AP) and chronic
      pancreatitis (CP) provide insight into causes and strategies for prevention and
      affect allocation of resources to its study and treatment. We sought to determine
      current and accurate incidences of AP and CP, along with the prevalence of CP, in
      children and adults in the United States. METHODS: We collected data from the
      Truven MarketScan Research Databases of commercial inpatient and outpatient
      insurance claims in the United States from 2007 through 2014 (patients 0-64 years
      old). We calculated the incidences of AP and CP and prevalence of CP based on
      International Classification of Diseases, 9th Revision diagnosis codes. Children
      were defined as 18 years or younger and adults as 19 to 64 years old. RESULTS:
      The incidence of pediatric AP was stable from 2007 through 2014, remaining at
      12.3/100,000 persons in 2014. Meanwhile, the incidence for adult AP decreased
      from 123.7/100,000 persons in 2007 to 111.2/100,000 persons in 2014. The
      incidence of CP decreased over time in children (2.2/100,000 persons in 2007 to
      1.9/100,000 persons in 2014) and adults (31.7/100,000 persons in 2007 to
      24.7/100,000 persons in 2014). The prevalences of pediatric and adult CP were
      5.8/100,000 persons and 91.9/100,000 persons, respectively, in 2014. Incidences
      of AP and CP increased with age. We found little change in incidence during the
      first decade of life but linear increases starting in the second decade.
      CONCLUSIONS: We performed a comprehensive epidemiologic analysis of privately
      insured, non-elderly adults and children with AP and CP in the United States.
      Changes in gallstone formation, smoking, and alcohol consumption, along with
      advances in pancreatitis management, may be responsible for the stabilization and
      even decrease in the incidences of AP and CP.

PMID- 29660324
TI  - Magnetic Resonance Imaging Proton Density Fat Fraction Associates With
      Progression of Fibrosis in Patients With Nonalcoholic Fatty Liver Disease.
AB  - Markers are needed to predict progression of nonalcoholic fatty liver disease
      (NAFLD). The proton density fat fraction, measured by magnetic resonance imaging
      (MRI-PDFF), provides an accurate, validated marker of hepatic steatosis; however,
      it is not clear whether the PDFF identifies patients at risk for NAFLD
      progression. We performed a follow-up study of 95 well-characterized patients
      with biopsy-proven NAFLD and examined the association between liver fat content
      and fibrosis progression. MRI-PDFF measurements were made at study entry
      (baseline). Biopsies were collected from patients at baseline and after a mean
      time period of 1.75 years. Among patients with no fibrosis at baseline, a higher
      proportion of patients in the higher liver fat group (MRI-PDFF >=15.7%) had
      fibrosis progression (38.1%) than in the lower liver fat group (11.8%) (P =
      .067). In multivariable-adjusted logistic regression models (adjusted for age,
      sex, ethnicity, and body mass index), patients in the higher liver fat group had
      a significantly higher risk of fibrosis progression (multivariable-adjusted odds
      ratio 6.7; 95% confidence interval 1.01-44.1; P = .049). Our findings associate
      higher liver fat content, measured by MRI-PDFF, with fibrosis progression.

PMID- 29660325
TI  - A1603P and K1617del, Mutations in beta-Cardiac Myosin Heavy Chain that Cause
      Laing Early-Onset Distal Myopathy, Affect Secondary Structure and Filament
      Formation In Vitro and In Vivo.
AB  - Over 20 mutations in beta-cardiac myosin heavy chain (beta-MHC), expressed in
      cardiac and slow muscle fibers, cause Laing early-onset distal myopathy (MPD-1),
      a skeletal muscle myopathy. Most of these mutations are in the coiled-coil tail
      and commonly involve a mutation to a proline or a single-residue deletion, both
      of which are predicted to strongly affect the secondary structure of the coiled
      coil. To test this, we characterized the effects of two MPD-1 causing mutations:
      A1603P and K1617del in vitro and in cells. Both mutations affected secondary
      structure, decreasing the helical content of 15 heptad and light meromyosin
      constructs. Both mutations also severely disrupted the ability of glutathione S
      transferase-light meromyosin fusion proteins to form minifilaments in vitro, as
      demonstrated by negative stain electron microscopy. Mutant eGFP-tagged beta-MHC
      accumulated abnormally into the M-line of sarcomeres in cultured skeletal muscle
      myotubes. Incorporation of eGFP-tagged beta-MHC into sarcomeres in adult rat
      cardiomyocytes was reduced. Molecular dynamics simulations using a composite
      structure of part of the coiled coil demonstrated that both mutations affected
      the structure, with the mutation to proline (A1603P) having a smaller effect
      compared to K1617del. Taken together, it seems likely that the MPD-1 mutations
      destabilize the coiled coil, resulting in aberrant myosin packing in thick
      filaments in muscle sarcomeres, providing a potential mechanism for the disease.

PMID- 29660326
TI  - Characterization of 16S rRNA Processing with Pre-30S Subunit Assembly
      Intermediates from E. coli.
AB  - Ribosomal RNA (rRNA) is a major component of ribosomes and is fundamental to the
      process of translation. In bacteria, 16S rRNA is a component of the small
      ribosomal subunit and plays a critical role in mRNA decoding. rRNA maturation
      entails the removal of intervening spacer sequences contained within the pre-rRNA
      transcript by nucleolytic enzymes. Enzymatic activities involved in maturation of
      the 5'-end of 16S rRNA have been identified, but those involved in 3'-end
      maturation of 16S rRNA are more enigmatic. Here, we investigate molecular details
      of 16S rRNA maturation using purified in vivo-formed small subunit (SSU) assembly
      intermediates (pre-SSUs) from wild-type Escherichia coli that contain precursor
      16S rRNA (17S rRNA). Upon incubation of pre-SSUs with E. coli S100 cell extracts
      or purified enzymes implicated in 16S rRNA processing, the 17S rRNA is processed
      into additional intermediates and mature 16S rRNA. These results illustrate that
      exonucleases RNase R, RNase II, PNPase, and RNase PH can process the 3'-end of
      pre-SSUs in vitro. However, the endonuclease YbeY did not exhibit nucleolytic
      activity with pre-SSUs under these conditions. Furthermore, these data
      demonstrate that multiple pathways facilitate 16S rRNA maturation with pre-SSUs
      in vitro, with the dominant pathways entailing complete processing of the 5'-end
      of 17S rRNA prior to 3'-end maturation or partial processing of the 5'-end with
      concomitant processing of the 3'-end. These results reveal the multifaceted
      nature of SSU biogenesis and suggest that E. coli may be able to escape
      inactivation of any one enzyme by using an existing complementary pathway.

PMID- 29660328
TI  - Antitumor efficacy of VP22-CD/5-FC suicide gene system mediated by lentivirus in
      a murine uveal melanoma model.
AB  - Uveal melanoma (UM) is the most common primary intraocular tumor in adults, which
      has high frequency of metastasis to the liver, typically causing a fatal outcome.
      Chemo-resistance remains a major obstacle in the therapeutic approach to UM,
      leaving limited choice for treating UM. Other possible treatments have been
      explored but the results are yet to be evident. To improve therapy for UM,
      transcriptional suicide genes were transfected into the OCM-1 cell line. In the
      current study, OCM-1 cells transfected with lentiviral-meditated EGFP, cytosine
      deaminase (CD)/EGFP, and VP22-CD/EGFP were established. Of the three groups, we
      examined the cell growth in vitro and in vivo by using the MTT method with cell
      culture media and MRI in murine UM models. According to our results, the cell
      proliferation in the transfected CD/EGFP group was slower than the non-suicide
      gene group. The VP22-CD/EGFP group manifested superior cell cytotoxicity than the
      CD/EGFP group. Further analysis of MRI and fluorescent imaging of the murine UM
      model identified significant differences in tumor volume among the three groups.
      Collectively, our study demonstrated that CD/5-FC is a potent therapeutic
      approach for UM. With the efficacy of VP22, suicide gene-induced cytotoxicity was
      superior to applying CD alone. Taken together, we concluded that novel therapy
      with the VP22-CD suicide gene may further contribute to treatment of UM.

PMID- 29660327
TI  - Crimp around the globe; patterns of collagen crimp across the corneoscleral
      shell.
AB  - Our goal was to systematically quantify the collagen crimp morphology around the
      corneoscleral shell, and test the hypothesis that collagen crimp is not uniform
      over the globe. Axial longitudinal cryosections (30 MUm) of three sheep eyes,
      fixed at 0 mmHg IOP, were imaged using polarized light microscopy to quantify the
      local collagen in 8 regions: two corneal (central and peripheral) and six scleral
      (limbus, anterior-equatorial, equatorial, posterior-equatorial, posterior and
      peripapillary). Collagen crimp period (length of one wave), tortuosity (path
      length divided by end-to-end length), waviness (SD of orientation), amplitude
      (half the peak to trough distance), and conformity (width of contiguous similarly
      oriented bundles) were measured in each region. Measurements were obtained on
      8216 collagen fiber bundles. When pooling measurements across the whole eye
      globe, the median crimp values were: 23.9 MUm period, 13.2 MUm conformity, 0.63
      MUm amplitude, 1.006 tortuosity, and 12.7 degrees  waviness. However, all
      parameters varied significantly across the globe. Median bundle periods in the
      central cornea, limbus, and peripapillary sclera (PPS) were 14.1 MUm, 29.5 MUm,
      and 22.9 MUm, respectively. Median conformities were 20.8 MUm, 14.5 MUm, and 15.1
      MUm, respectively. Median tortuosities were 1.005, 1.007, and 1.007,
      respectively. Median waviness' were 11.4 degrees , 13.2 degrees , and 13.2
      degrees , respectively. Median amplitudes were 0.35 MUm, 0.87 MUm, and 0.65 MUm,
      respectively. All parameters varied significantly across the globe. All regions
      differed significantly from one another on at least one parameter. Regions with
      small periods had large conformities, and bundles with high tortuosity had high
      waviness and amplitude. Waviness, tortuosity, and amplitude, associated with
      nonlinear biomechanical behavior, exhibited "double hump" distributions, whereas
      period and conformity, representing tissue organization, were substantially
      different between sclera and cornea. Though the biomechanical implications and
      origin of the patterns observed remain unclear, our findings of well-defined
      patterns of collagen crimp across the corneoscleral shell, consistent between
      eyes, support the existence of mechanisms that regulate collagen characteristics
      at the regional or smaller levels. These results are experimental data necessary
      for more realistic models of ocular biomechanics and remodeling.

PMID- 29660329
TI  - Aquaporin 5 promotes corneal wound healing.
AB  - Aquaporins (AQPs), ordinarily regarded as water channels, have recently been
      shown to participate in other cellular functions such as cell-to-cell adhesion,
      cell migration, cell proliferation etc. The current investigation was undertaken
      to find out whether AQP5 water channel plays a role in corneal epithelial wound
      healing. Expression of AQP5 in mouse cornea and transfected Madin-Darby canine
      kidney (MDCK) cells was detected using immunofluorescence or EGFP tag. Cell
      migration and proliferation, the two major events in wound healing, were studied
      in vitro using cell culture scratch-wound healing model and cell proliferation
      assay, in vivo by conducting wound healing experiments on corneas of wild-type
      and AQP5 knockout mouse model and ex vivo on corneal epithelial cells isolated
      from wild type and AQP5 knockout mice. MDCK cells stably expressing AQP5 showed
      significantly higher levels of cell migration and proliferation compared to
      control cells. Likewise, corneal epithelial cells of wild type mouse with innate
      AQP5 exhibited faster wound healing than those of AQP5 knockout in vivo and under
      ex vivo culture conditions. In vitro, in vivo and ex vivo studies showed that
      presence of AQP5 improved cell migration, proliferation and wound healing. The
      data collected suggest that AQP5 plays a significant role in corneal epithelial
      wound healing.

PMID- 29660330
TI  - MiRNA-92a protects pancreatic B-cell function by targeting KLF2 in diabetes
      mellitus.
AB  - AIMS: diabetes mellitus is one of the most common metabolic diseases worldwide
      characterized by insulin resistance and pancreatic beta cell dysfunction. miRNA
      plays an important role in DM. In previous studies, miRNA-92a could function as
      targets for innovative precision medicines to reduce T1D islet autoimmunity.
      However, the relationship between miRNA-92a and pancreatic beta cell dysfunction
      remains unknown. The aim of the study was to investigate the role of miRNA-92a in
      pancreatic beta cell dysfunction. METHODS: Apoptosis, proliferation, insulin
      secretion and cell survival rate were detected to evaluate the function of miRNA
      92a. RESULTS: we found that miRNA-92a could inhibit apoptosis induced by high
      glucose environment and increase the insulin secretion and proliferation.
      Moreover, we identify the KLF2 as direct target of miRNA-92a, suggesting that
      miRNA-92a may function through regulating KLF2. CONCLUSION: Altogether, we
      verified the function and mechanism of miRNA-92a and provide evidence that miRNA
      92a may serve a potential candidate for the clinical treatment for DM.

PMID- 29660331
TI  - Biophysical characterization of actin bundles generated by the Chlamydia
      trachomatis Tarp effector.
AB  - Chlamydia trachomatis entry into host cells is mediated by pathogen-directed
      remodeling of the actin cytoskeleton. The chlamydial type III secreted effector,
      translocated actin recruiting phosphoprotein (Tarp), has been implicated in the
      recruitment of actin to the site of internalization. Tarp harbors G-actin binding
      and proline rich domains required for Tarp-mediated actin nucleation as well as
      unique F-actin binding domains implicated in the formation of actin bundles.
      Little is known about the mechanical properties of actin bundles generated by
      Tarp or the mechanism by which Tarp mediates actin bundle formation. In order to
      characterize the actin bundles and elucidate the role of different Tarp domains
      in the bundling process, purified Tarp effectors and Tarp truncation mutants were
      analyzed using Total Internal Reflection Fluorescence (TIRF) microscopy. Our data
      indicate that Tarp mediated actin bundling is independent of actin nucleation and
      the F-actin binding domains are sufficient to bundle actin filaments.
      Additionally, Tarp-mediated actin bundles demonstrate distinct bending stiffness
      compared to those crosslinked by the well characterized actin bundling proteins
      fascin and alpha-actinin, suggesting Tarp may employ a novel actin bundling
      strategy. The capacity of the Tarp effector to generate novel actin bundles
      likely contributes to chlamydia's efficient mechanism of entry into human cells.

PMID- 29660332
TI  - DUSP14 knockout accelerates cardiac ischemia reperfusion (IR) injury through
      activating NF-kappaB and MAPKs signaling pathways modulated by ROS generation.
AB  - Inflammation and oxidative stress are significantly involved in the progression
      of a variety of diseases, including myocardial ischemia/reperfusion (IR). In the
      present study, we hypothesized a protective role of dual-specificity phosphatase
      14 (DUSP14) in myocardial IR, as well as the underlying molecular mechanism. The
      results indicated that DUSP14 was down-regulated following cardiac IR injury.
      Subsequently, the wild type (WT) and DUSP14-knockout (KO) mice were included to
      further reveal the potential role of DUSP14 in cardiac IR injury progression.
      DUSP14-KO mice exhibited increased infarction area and elevated apoptosis, as
      evidenced by the increased TUNEL-positive cells in ischemia heart following
      reperfusion compared to WT mice. Further, DUSP14-KO significantly aggregated
      cardiac dysfunction of mice after IR injury. Cardiac IR injury to DUSP14-KO mice
      led to markedly increased expression of pro-inflammatory cytokines and activated
      nuclear factor-kappaB (NF-kappaB) pathway in the heart in comparison to WT mice.
      Meanwhile, mitogen-activated protein kinases (MAPKs), including p38, ERK1/2 and
      JNK, were significantly activated by DUSO14-KO in mice after IR injury. Compared
      to WT mice, DUSP14-KO mice showed markedly increased oxidative stress markers in
      cardiac tissues, including malondialdehyde (MDA), NADPH oxidase-4 (NOX4) and p47,
      while decreased activities or expressions of anti-oxidants, such as glutathione
      (GSH), glutathione peroxidase (GPx), glutathion reductases (GR), superoxide
      dismutase (SOD) and hemeoxygenase-1 (HO-1). DUSP14-knockdown (KD) in primary
      cardiomyocytes using its specific siRNA sequence elevated hypoxia and
      reoxygenation (HR)-induced activation of NF-kappaB and MAPKs signaling pathways,
      and reactive oxygen species (ROS) generation. Intriguingly, pre-treatment of ROS
      scavenger, N-acetylcysteine (NAC), markedly abolished DUSP14-KD-augmented NF
      kappaB and MAPKs activation in HR-stimulated primary cardiomyocytes. Together,
      the results above indicated that DUSP14 might be served as a positive regulator
      to attenuate cardiac IR injury. Suppressing DUSP14 exacerbated cardiac injury
      through activating NF-kappaB and MAPKs signaling pathways regulated by ROS
      production. Thus, DUSP14 could be a valuable target for developing treatments for
      myocardial IR injury.

PMID- 29660333
TI  - Epitope-based ligation of ICAM-1: Therapeutic target for protection against the
      development of rheumatoid arthritis.
AB  - Identification of a particular epitope on the domain 2 of human ICAM-1 led us to
      focus on its role in the treatment of rheumatoid arthritis (RA). Key observations
      from our previous xenotransplantation research included the generation of
      tolerogenic DCs, antigen-specific T-cell tolerance, and reduced production of
      inflammatory cytokines. The critically important point is the fact that it works
      initially on DC maturation. Ligation of this epitope with a recognizing antibody,
      MD-3, was also able to create a tolerogenic environment in RA in a manner sililar
      to that created by xenotransplantation. In this study, we noted that the disease
      progression, in terms of arthritis score and histopathology of joints, was
      significantly less severe in the MD-3-treated group than in the vehicle-treated
      group. Defective production of IL-6 and reduced proliferation of collagen
      specific T cells were most remarkable laboratory findings. This type of ligation
      has a greater advantage over other types of therapeutics, in a sense that simple
      injection of this antibody inhibits antigen-specific T cell response. Due to the
      possibility of viral infection in this process, we regularly monitored
      cytomegalovirus reactivation status without detection of any viral gene
      replication. We are hoping that remarkable specializations that this interaction
      has, would be a promising target for therapeutic antibody in RA.

PMID- 29660334
TI  - Fatty acids modulate the efficacy of lutein in cataract prevention: Assessment of
      oxidative and inflammatory parameters in rats.
AB  - BACKGROUND: Effects of lutein (L) and fatty acids [linoleic acid (LA),
      eicosapentaenoic acid (EPA)+docosahexaenoic acid (DHA) and oleic acid (OA)] on
      oxidative stress and inflammation in cataract were assessed. METHODS: Cataract
      was induced in male Wistar rat pups (11 days old) by giving a single dose of
      sodium selenite (25 MUM/kg body weight) by IP. Lutein (1.3 MUmol/kg body weight)
      was given one day before and five days after selenite injection as a micelle with
      7.5 mM LA, or 7.5 mM EPA + DHA or 7.5 mM OA. Serum and lens oxidative stress and
      inflammatory parameters having a bearing cataract were assessed. RESULTS: Serum
      and lens nitric oxide, MDA and protein carbonyls were significantly (p < 0.05)
      increased in cataract compared to control and experimental groups. Catalase, SOD,
      glutathione peroxidase and glutathione transferase activity and glutathione level
      in serum and lens of cataract group were significantly (p < 0.05) decreased.
      Serum eicosanoids (PGE2, LTB4, and LTC4) and cytokines (CRP, TNF-alpha, IL1-beta,
      and MCP-1) were significantly (p < 0.05) increased in cataract. The activity of
      cPLA2 and Cox-2 in cataract lens was higher (p < 0.05) compared to other groups.
      EP-1, NOS-2 and NF-kB expression were higher (p < 0.05) in cataract. The ratio of
      water insoluble to water soluble protein was increased in cataract lens. Group
      administered with L + EPA + DHA exhibited highest cataract prevention compared to
      L + LA and L + OA. Pups given lutein with EPA + DHA had the highest amount of
      lutein in the lens. CONCLUSIONS: The anti-cataract activity of lutein was
      influenced by fatty acids and found to be highest with EPA + DHA compared to LA
      or OA.

PMID- 29660335
TI  - mTOR up-regulation of BEX4 promotes lung adenocarcinoma cell proliferation by
      potentiating OCT4.
AB  - Previously, BEX family members have been reported to participate in cancer
      development. However, little is known about the role of BEX4 in lung
      adenocarcinoma (LAC). Here, we found that BEX4 was over-expressed in LAC tissues
      compared with adjacent tissues. LAC tissues from metastatic patients exhibited
      higher expression of BEX4 comparing to those from non-metastatic ones. In vitro,
      BEX4 ectopic expression accelerated the proliferation of both A549 and H1975
      cells. By contrast, knockdown of BEX4 suppressed the proliferation of A549 and
      H1975 cells. BEX4 positively regulated the expression of OCT4, silencing of which
      reduced the proliferation of A549 and H1975 cells with over-expressed BEX4.
      Additionally, mTOR activation, which is frequently observed in LAC, potentiated
      BEX4 depending on mTORC1 but not mTORC2. BEX4 abundance dictated the sensitivity
      of A549 and H1975 cells to rapamycin treatment. Our findings reveal that BEX4 is
      an oncogene in LAC and may contribute to the hyper-active mTOR-induced LAC
      development.

PMID- 29660336
TI  - MicroRNA-155 inversely correlates with esophageal cancer progression through
      regulating tumor-associated macrophage FGF2 expression.
AB  - Esophageal cancer (EC) is one of the most common malignancies with high incidence
      and mortality. Tumor-associated macrophages (TAMs) in the tumor microenvironment
      have been linked to the accelerated tumor progression. MicroRNAs (miR) are 19-25
      nucleotide-long, noncoding RNA molecules, functioning as modulators of gene
      expression, and mediate a variety of biological functions, including tumor
      growth. In the present study, the effects and molecular mechanism of miR-155 in
      TAMs isolated from EC were explored. The expression of miR-155 and fibroblast
      growth factor-2 (FGF2) in EC tissues and cell lines were analyzed using reverse
      transcription-quantitative PCR (qRT-PCR) and western blot assays. TAMs were also
      transfected with the described constructs. Following, the culture medium from
      TAMs was collected for further analysis. The released FGF2, and inflammatory
      cytokines were quantified using ELISA. The cell viability, migrated and invaded
      levels were calculated through Cell Counting kit-8 (CCK8), and transwell
      analysis. Moreover, human umbilical vein endothelial cells (HUVEC) vasculature
      formation was determined using matrigel angiogenesis analysis. The results
      indicated that miR-155 expression was decreased in EC tissues and cell lines,
      while FGF2 expression was increased in comparison to those in the normal control
      group. Moreover, miR-155 mimics transfection up-regulated tumor necrosis factor
      alpha (TNF-alpha), interleukin (IL)-12 and inducible nitric oxide synthase
      (iNOS), while down-regulated IL-10, Arginase-1 (Arg-1) and IL-22 levels in the
      culture medium from TAMs. And enhancing miR-155 expression in TAMs suppressed the
      cell viability, migration and invasion of ECA109 cells and reduced the
      angiogenesis. Nevertheless, over-expressing FGF2 abolished the role of miR-155 in
      cancer cell survival, migration, invasion as well as angiogenesis. Our findings
      indicated that miR-155-regulated FGF2 expression from TAMs suppressed EC cell
      proliferation, migration, invasion and inhibited vasculature formation. Thus, miR
      155-modulated FGF2 might be a potential therapeutic target to prevent EC
      progression.

PMID- 29660338
TI  - Different molecular mechanisms of HTLV-1 and HIV LTR activation by TPA.
AB  - HTLV-1 and HIV-1 are retroviruses involved in different human diseases. However,
      following infection, these viruses inter into a latent state. Tax and Tat are
      regarded as trans-activators of HTLV-1 and HIV-1 respectively. As it known,
      during the latent state the infected cells contain low Tax and Tat protein
      levels, so the activation of these viruses must be independent of these proteins.
      Here we focus on exploring the mechanism of activation of these viruses by 12-O
      tetradecanoylphorbol-13-acetate (TPA), which is a potent activator of protein
      kinase C (PKC) and considered as a stress-inducing agent. Our results showed that
      short exposure to TPA considerably stimulated only the HIV-1 LTR expression,
      while long exposure stimulated only the HTLV-1 LTR and that their activation is
      agonized or antagonized by PKC respectively. It was found that TPA induced
      interaction between the transcriptional factors Sp1 and P53 producing Sp1-p53
      complex which strongly interacted with c-Jun only after short exposure to TPA. In
      addition, TPA treatment highly induced the expression of CREB which attached to
      the Sp1-p53 complex mainly after a long exposure to TPA. A strong binding of sp1,
      p53 and CREB proteins with HTLV-1 LTR and strong binding of NF-kappaB with HIV-1
      LTR were observed after long (24 h) and short (6 h) exposures to TPA respectively
      by Chip assay. These results support the possibility that sp1, p53 and CREB are
      involved in the TPA induced HTLV-1 LTR expression while TPA activation of HIV-1
      LTR seems to be dependent on PKC activity through the NF-kappaB pathway.

PMID- 29660337
TI  - Effect of betulinic acid and its ionic derivatives on M-MuLV replication.
AB  - Murine leukemia virus (MuLV) is a retrovirus known causing leukemia and
      neurological disorders in mice, and its viral life cycle and pathogenesis have
      been investigated extensively over the past decades. As a natural antiviral
      agent, betulinic acid is a pentacyclic triterpenoid that can be found in the bark
      of several species of plants (particularly the white birch). One of the hurdles
      for betulinic acid to release its antiviral potency is its poor water solubility.
      In this study, we synthesized more water-soluble ionic derivatives of betulinic
      acid, and examined their activities against Moloney MuLV (M-MuLV). The mouse
      fibroblast cells stably infected with M-MuLV, 43D cells, were treated with
      various doses of betulinic acids and its derivatives, and the viral structural
      protein Gag in cells and media were detected by western blots. Two ionic
      derivatives containing the benzalkonium cation were found to inhibit the virus
      production into media and decreased Gag in cells. However, a cell proliferation
      assay showed that the benzalkonium cation inhibited the growth of 43D cells,
      suggesting that our ionic derivatives limited virus production through the
      inhibition of metabolism in 43D cells. Interestingly, all of these betulinic acid
      compounds exhibited a minimum impact on the processing and release of Gag from
      43D cells, which outlines the differences of viral maturation between MuLV and
      human immunodeficiency virus.

PMID- 29660339
TI  - GLUT5 increases fructose utilization and promotes tumor progression in glioma.
AB  - Fructose is now such an important component of human diets, and several studies
      have found that some cancer cells could utilize fructose to overcome low glucose
      micro-environment, but the study on the role of fructose in glioma is rare. To
      explore the role of fructose in glioma, we detected the proliferation and colony
      formation ability of glioma cells in fructose medium, and found that the
      abilities of proliferation and colony formation of glioma cells in fructose
      medium were similar with abilities in glucose medium, however, fructose just
      partly restored proliferation ability of normal glial cells. To explore the
      mechanism, we compared the expression level of GLUT5 (Glucose transporter type 5)
      in these cell lines, and the results showed that glioma cell lines had higher
      GLUT5 expression than normal glial cell lines. And knockdown of GLUT5 could
      significantly inhabit cell proliferation of glioma cells in fructose medium.
      Furthermore, we found that GLUT5 was also higher expressed in glioma tissues, and
      GLUT5 expression correlated significantly with glioma malignancy and poor
      survival of glioma patients (p < 0.01). In addition, we also demonstrated that
      knockdown of GLUT5 could significantly inhabit tumor proliferation in vivo, and
      intake fructose could increase tumor volume prominently. Taken together, our data
      show that fructose can be used by glioma cells, and restrict the fructose intake
      or targeting GLUT5 could be efficacious strategies in glioma.

PMID- 29660340
TI  - Alteration of global protein SUMOylation in neurons and astrocytes in response to
      Alzheimer's disease-associated insults.
AB  - SUMOylation, a post-translational modification of lysine residues by small
      ubiquitin-like modifier (SUMO) proteins, has been implicated in the pathogenesis
      of neurodegenerative disorders including Alzheimer's disease (AD), and in neuron-
      and astrocyte-specific physiological functions. Global SUMOylation is increased
      in the AD mouse brain in the pre-plaque-forming stage but returns to wild-type
      levels in the plaque-bearing stage. To clarify the reason for the transient
      change in SUMOylation, we analyzed the alteration of global SUMOylation induced
      by AD-associated cytotoxic stimuli in neurons and astrocytes individually. In
      neurons, amyloid beta42 oligomers induced some but not significant increase in
      levels of SUMO1-modified proteins. Both hydrogen peroxide and glutamate
      significantly reduced SUMO1-modified protein levels. These changes were more
      prominent in neurons than in astrocytes. The opposite effect of Abeta and
      oxidative/excitotoxic stimuli on SUMO1 modification may cause the pathological
      stage-associated change in the level of SUMO-modified proteins in the AD mouse
      brain.

PMID- 29660341
TI  - Evaluation of synthetic promoters in Physcomitrella patens.
AB  - Securing a molecular toolbox including diverse promoters is essential for genome
      engineering. However, native promoters have limitations such as the available
      number or the length of the promoter. In this work, three short synthetic
      promoters were characterized by using the yellow fluorescent protein Venus. All
      of the tested promoters were active and showed higher mRNA expression than
      housekeeping gene PpAct7, and similar protein expression level to the AtUBQ10
      promoter. This study shows that few cis-regulatory elements are enough to
      establish a strong promoter for continuous expression of genes in plants. Along
      with this, the study enhance the number of available promotors to be used in P.
      patens. It also demonstrates the potential to construct multiple non-native
      promoters on demand, which would aid to resolve one bottleneck in multiple
      pathway expression in P. patens and other plants.

PMID- 29660342
TI  - Investigation of TRPV1 loss-of-function phenotypes in TRPV1 Leu206Stop mice
      generated by N-ethyl-N-nitrosourea mutagenesis.
AB  - N-ethyl-N-nitrosourea (ENU) random mutagenesis was used to generate a mouse model
      for the analysis of the transient receptor potential vanilloid 1 (TRPV1) cation
      channel. A transversion from T->A in exon 4 led to a Leu206Stop mutation
      generating a loss-of-function mutant. The TRPV1 agonist capsaicin was used to
      analyze functional and nociceptive parameters in vitro and in vivo in TRPV1
      Leu206Stop mice and congenic C3HeB/FeJ controls. Capsaicin-induced [Ca2+]i
      changes in small diameter DRG neurons were significantly diminished in TRPV1
      Leu206Stop mice and administration of capsaicin induced neither hypothermia nor
      nocifensive behaviour in vivo. TRPV1 Leu206Stop mice were tested in the spinal
      nerve ligation of mononeuropathic pain and developed mechanical hypersensitivity
      two weeks after nerve injury. In the open field test, a significant increase in
      spontaneous locomotion was detected in TRPV1 Leu206Stop mice as compared to
      wildtype controls. TRPV1 knockout mice have been reported to carry a similar
      phenotype regarding capsaicin-evoked responses in vitro and in vivo. However, in
      contrast to TRPV1 Leu206Stop mice, TRPV1 knockout mice did not differ in
      spontaneous locomotion as compared to congenic C57BL/6 mice, suggesting subtle
      ENU-dependent or independent strain differences between TRPV1 Leu206Stop mice and
      their wildtype controls. In summary, these data revealed a target-related (i.e.
      capsaicin-evoked) phenotype of TRPV1 Leu206Stop mice closely resembling that of
      published TRPV1 knockout mice. However, since ENU-mutant mice are congenic with
      the mouse strain initially used in random mutagenesis, direct phenotypic
      comparison with the respective wildtype controls is possible, and the time
      consuming backcrossing in lines with targeted mutations is avoided.

PMID- 29660343
TI  - Transcription of blunt snout bream (Megalobrama amblycephala) HIF3alpha and its
      localization in the nucleus under both normoxic and hypoxic conditions.
AB  - Although hypoxia-inducible factor (HIF) 1alpha and 2alpha function as master
      regulators of the transcriptional response to hypoxia, the function of HIF3alpha
      and its responses to hypoxic stress remain unclear in teleost fish. Here, we
      characterized the HIF3alpha cDNA in hypoxia-sensitive blunt snout bream
      (Megalobrama amblycephala), with 3059 bp length, consisting of an open reading
      frame (ORF) encoding 643 amino acid residues. Blunt snout bream HIF3alpha mRNA
      was stably expressed during stages of embryonic development and in adult tissues.
      After a 4 h hypoxia stress, HIF3alpha mRNA of the juvenile fish was significantly
      upregulated in the liver, brain, and kidney, and restored to the pretreatment
      levels after a 24 h recovery. When tagged with enhanced green fluorescent protein
      (EGFP) and transfected into cultured HeLa cells, blunt snout bream HIF3alpha was
      mainly distributed in the nucleus under normoxia. Treatment of the cells with
      CoCl2 to mimic hypoxic conditions showed that there was no effect about the
      nuclear localization of HIF3alpha but a statistically significant increase in
      HIF3alpha protein levels. A nuclear localization signal (NLS) sequence at the C
      terminus of HIF3alpha may exert positive effects in the process of nuclear
      localization. These results suggest that blunt snout bream HIF3alpha could be
      involved in different physiological functions under normoxia and hypoxia
      conditions.

PMID- 29660344
TI  - Hyperhomocysteinemia and hyperandrogenemia share PCSK9-LDLR pathway to disrupt
      lipid homeostasis in PCOS.
AB  - Women with polycystic ovary syndrome (PCOS) are at increased risk of
      cardiovascular diseases (CVD); however, the independent role of PCOS in the
      incident CVD remains unknown. There are reports that hyperhomocysteinemia (HHcy),
      a potential cause of CVD, is frequently associated with PCOS. The present study
      investigates the independent attributes of hyperandrogenemia (HA), the integral
      associate of PCOS, and HHcy in causing atherogenic dyslipidemia. Twenty-five-day
      old rats were treated with homocysteine (Hcy) at 50 mg/kg/day dose level for 12
      weeks. The HepG2 cell lines transfected with siRNA directed to PCSK9 were
      challenged with Hcy, homocysteine thiolactone (HTL), testosterone, 5alpha
      dihydroxytestosterone (5alpha-DHT), or estradiol for 24 h. Rats administered with
      Hcy developed HHcy and displayed PCOS-like phenotypes with adversely altered
      lipid homeostasis and attenuated PI3K-AKT and Wnt signalling cascade.
      Overexpression of steroidogenic acute regulatory protein (StAR) and down
      regulated expression of Aromatase together with elevated testosterone level
      marked the state of HA. In culture, the HepG2 cells responded independently to
      Hcy, HTL, testosterone, and 5alpha-DHT by an overt expression of PCSK9 and down
      regulated expression of LDLR. The effect was magnified under the combined
      influence of Hcy and androgen(s). Estradiol, by contrast, exhibited the reverse
      effect. The findings suggest that HA may independently attribute to an increased
      cardiovascular risk in PCOS; however, the coexistence of HHcy catalyzes the risk
      further.

PMID- 29660345
TI  - A novel heme oxygenase-1 splice variant, 14kDa HO-1, promotes cell proliferation
      and increases relative telomere length.
AB  - Alternative splicing is a routine phenomenon which greatly increases the
      diversity of proteins in eukaryotic cells. In humans, most multi-exonic genes are
      alternatively spliced and their splice variants confer distinct functions. Heme
      oxygenase-1 (HO-1, 32 kDa) is an inducible stress responsive protein, which
      possesses multiple functions in many cellular processes. In the current study, we
      identified a novel alternative splice isoform of 14 kDa HO-1 generated through
      exclusion of exon 3, and it is highly expressed in immortalized cells. In
      contrast to nuclear accumulation of the full-length 32 kDa HO-1, the novel 14 kDa
      HO-1 isoform is retained in the cytoplasm under ultraviolet (UV) irradiation.
      Interestingly, the 14 kDa HO-1 is shown to promote cell proliferation and an
      increase in relative telomere lengths in vivo and in vitro. Thus, we are pioneer
      to report and confirm the presence of a novel splice form of HO-1 and its
      distinct role in modulating telomere length and tumor growth.

PMID- 29660346
TI  - Wash-free and selective imaging of epithelial cell adhesion molecule (EpCAM)
      expressing cells with fluorogenic peptide ligands.
AB  - Detection of the cells expressing an epithelial cell adhesion molecule (EpCAM) is
      a crucial step to identify circulating tumor cells (CTCs) from blood. To detect
      the EpCAM, we here designed and synthesized a series of fluorogenic peptides.
      Specifically, we functionalized an EpCAM-binding peptide, Ep114, by replacing its
      amino acids to an aminophenylalanine that was modified with environmentally
      sensitive 7-nitro-2,1,3-benzoxadiazole (NBD-amPhe). Among six synthesized
      peptides, we have found that two peptides, Q4X and V6X (X represents NBD-amPhe),
      retain the Ep114's binding ability and specifically mark EpCAM-expressing cells
      by just adding these peptides to the cultivation medium. Our wash-free,
      fluorogenic peptide ligands would boost the development of next generation
      devices for CTC diagnoses.

PMID- 29660347
TI  - Detection and quantification of shrimp hemocyte iridescent virus by TaqMan probe
      based real-time PCR.
AB  - Shrimp hemocyte iridescent virus (SHIV) is a recently reported shrimp virus,
      which threats the cultured white-leg shrimp Litopenaeus vannamei and can cause
      huge economic loss in shrimp farming industry in China. A quantitative real time
      polymerase chain reactio (qPCR) assay was developed using a TaqMan probe to
      detect and quantify SHIV. A pair of qPCR primers, which amplify a 188 bp DNA
      fragment, and a TaqMan probe were selected from ATPase gene (ORF114R) of the SHIV
      genome. The primers and TaqMan probe used in this assay were shown to be specific
      for SHIV and did not react with White spot syndrome virus (WSSV), Infectious
      hypodermal and hematopoietic necrosis virus (IHHNV), Hepatopancreatic parvovirus
      (HPV), Vibrio parahaemolyticus causing acute hepatopancreatic necrosis disease
      (VPAHPND), and Enterocytozoon hepatopenaei (EHP), or healthy shrimp DNA. The
      detection limit of the qPCR method was as low as 4 copies per reaction. The
      diagnostic sensitivity and the diagnostic specificity of the qPCR compared with
      nested PCR were 95.3% and 99.2%, respectively. The resulting standard curves
      showed high correlation coefficient values (R2 = 0.998) in the range of 4 * 109
      to 4 * 100 DNA copies/reaction. Test of farm samples showed that SHIV was
      detected in L. vannamei, Fenneropenaeus chinensis and Macrobrachium rosenbergii
      contained SHIV ranged from 1.21E+02 to 7.95E+07 copies (MUg DNA)-1. Quantitative
      detection of different tissues in artificial infected shrimp showed that
      haemolymph contained the highest SHIV load and muscle contained lowest SHIV load.

PMID- 29660348
TI  - Chamber-Made: Mural Endocarditis.

PMID- 29660349
TI  - Sickle Cough: A Case of Nonresolving Pneumonia.

PMID- 29660350
TI  - Acute Onset Unilateral Proptosis.

PMID- 29660351
TI  - Association of Anemia with Venous Thromboembolism in Acutely Ill Hospitalized
      Patients: An APEX Trial Substudy.
AB  - BACKGROUND: Anemia is a common finding and independent predictor for adverse
      outcomes in hospitalized patients with medical illness. It remains unclear
      whether anemia is a risk factor for venous thromboembolism and whether the
      presence of anemia can refine risk assessment for prediction of venous
      thromboembolism, thereby adding incremental utility to a validated model.
      METHODS: In the Acute Medically Ill Venous Thromboembolism Prevention with
      Extended Duration Betrixaban trial (APEX), 7513 hospitalized medical patients
      were randomized to receive either betrixaban or standard-of-care enoxaparin for
      thromboprophylaxis. Baseline hemoglobin concentrations were obtained in 6861
      patients, with a follow-up of 77 days. Symptomatic venous thromboembolism events,
      including symptomatic deep vein thrombosis, pulmonary embolism, and venous
      thromboembolism-related mortality, were compared between low-hemoglobin and
      normal-hemoglobin groups (normal range: 12.5-17.0 g/dL for males and 11.0-15.5
      g/dL for females). The relationship between anemia and venous thromboembolism
      events was assessed by fitting a univariable and multivariable logistic
      regression model composed of thromboprophylaxis and risk factors. Venous
      thromboembolism risk refinement by hemoglobin measurement was evaluated in the
      International Medical Prevention Registry on Venous Thromboembolism (IMPROVE)
      risk assessment model. RESULTS: Low hemoglobin at baseline was associated with a
      greater risk of symptomatic venous thromboembolism (relative risk [RR] 1.94 [95%
      confidence interval, 1.27-2.98]; P = .002), symptomatic deep vein thrombosis (RR
      2.29 [1.12-4.68]; P = .019), and nonfatal pulmonary embolism (RR 2.63 [1.22
      5.65]; P = .010) but not venous thromboembolism-related mortality (RR 1.47 [0.71
      3.04]; P = .30). After adjusting for thromboprophylaxis, history of previous
      venous thromboembolism, intensive or coronary unit admission, and D-dimer, low
      hemoglobin (as a categorical or continuous variable) remained associated with an
      increased likelihood of venous thromboembolism (adjusted odds ratio 1.71 [95%
      confidence interval, 1.09-2.69]; P = .020). Low hemoglobin also improved risk
      discrimination and reclassification after inclusion in the IMPROVE model.
      CONCLUSIONS: Anemia was independently associated with a greater risk of
      symptomatic venous thromboembolism among acutely ill medical patients despite the
      provision of thromboprophylaxis. Hemoglobin measurement also improved risk
      stratification by the IMPROVE venous thromboembolism risk score.

PMID- 29660352
TI  - Outcomes in a Community-Based Intensive Cardiac Rehabilitation Program:
      Comparison with Hospital-Based and Academic Programs.
AB  - BACKGROUND: The purpose of this study was to test the hypothesis that a community
      based intensive cardiac rehabilitation program could produce positive changes in
      risk factor profile and outcomes in an at-risk population. METHODS: Participants
      seeking either primary or secondary coronary artery disease prevention
      voluntarily enrolled in the 12-week intensive cardiac rehabilitation program.
      Data were obtained at baseline and 6-12 months after completion of the program.
      RESULTS: A total of 142 individuals, mean age 69 years, completed the Heart
      Series between 2012 and 2016. Follow-up data were available in 105 participants
      (74%). Participants showed statistically significant improvements in mean weight
      (165 to 162 lbs, P = .0005), body mass index (26 to 25 kg/m2, P = .001), systolic
      blood pressure (126 to 122 mm Hg, P = .01), diastolic blood pressure (73 to 70 mm
      Hg, P = .0005), total cholesterol (175 to 168 mg/dL, P = .03), low-density
      lipoprotein cholesterol (LDL-C) (100 to 93 mg/dL, P = .005), LDL-C/high-density
      lipoprotein cholesterol (HDL-C) ratio (1.8 to 1.6, P = .005), and cholesterol/HDL
      C ratio (3.2 to 3.0, P = .003). Changes in HDL-C, triglycerides, and fasting
      blood glucose did not reach statistical significance, but all trended in
      favorable directions. Adverse cardiovascular disease outcomes were rare (one
      stent placement, no deaths). CONCLUSIONS: A total of 105 participants completed
      our 12-week community-based intensive cardiac rehabilitation program and showed
      significant positive changes in several measures of cardiac risk, with only 1
      adverse event. These results compare favorably with those of hospital-based and
      academic institutional programs.

PMID- 29660353
TI  - Serious Cover-Up: Hodgkin's Lymphoma Masked by Organizing Pneumonia.

PMID- 29660354
TI  - Novel Treatment for Anastomotic Leak After Ivor-Lewis Esophagectomy.
AB  - Intrathoracic anastomotic leaks after esophagogastrostomy occur frequently, often
      resulting in prolonged hospitalization and delays in advancing oral nutrition and
      hydration. Management of anastomotic esophageal leaks vary based on time of
      occurrence to time of intervention, condition of the patient, and location.
      Conservative approaches such as endovascular clips and endovascular stents have
      gained momentum in addressing esophageal leaks and fistulas, replacing the
      original paradigm of surgical approach as initial management. More recently, the
      use of intraluminal and intracavitary endoscopic vacuum-assisted therapy has been
      used to treat esophageal leaks successfully. We present a novel treatment method
      for anastomotic leaks using a modified percutaneous endoscopic gastrostomy tube.

PMID- 29660355
TI  - Intrapleural Therapy for Empyema in the Setting of a Bronchopleural Fistula: A
      Novel Use of an Intrabronchial Valve.
AB  - Postsurgical empyema with bronchopleural fistula can be difficult to manage. We
      present a patient with postoperative empyema with bronchopleural fistula who was
      successfully treated nonoperatively by placing an intrabronchial valve to address
      the bronchopleural fistula, which allowed for safe administration of intrapleural
      fibrinolytics and antibiotics for definitive treatment of the empyema. Although
      the presence of a bronchopleural fistula is considered a contraindication to the
      administration of intrapleural tissue plasminogen activator and
      deoxyribonuclease, this case demonstrates a novel use of the intrabronchial valve
      that allowed these medications to be used.

PMID- 29660356
TI  - Reply.

PMID- 29660357
TI  - Reply.

PMID- 29660358
TI  - A Table Mounted Cardiopulmonary Bypass System for Pediatric Cardiac Surgery.
AB  - Systemic inflammatory response and hemodilution are prominent factors associated
      with cardiopulmonary bypass and result in increased morbidity and mortality in
      children. Miniaturized systems have evolved to decrease such effects and restrict
      use of blood products, especially in the neonatal population. We have developed a
      table mounted cardiopulmonary bypass system that allows closer proximity of the
      system to the patient with consequent decrease in priming volumes, hemodilution,
      and its associated effects, and contributes to development into an ideally
      bloodless surgical approach.

PMID- 29660359
TI  - Transcatheter Mitral Valve-in-Valve Dislocation: A Rescue Strategy.
AB  - In the transcatheter aortic valve replacement era, transapical valve-in-valve
      mitral valve implantation is considered an alternative treatment for high-risk
      patients with degenerated mitral bioprosthesis. We report an unusual strategy to
      remedy the potentially fatal complication of the mitral prosthesis migration into
      the aortic arch. The dislocated prosthesis was successfully stabilized in the
      aortic arch with a bare aortic stent, ensuring adequate perfusion of epiaortic
      vessels.

PMID- 29660360
TI  - Spontaneous Coronary Artery Dissection in a Woman: Surgical Treatment and
      Angiographic Follow-Up.
AB  - Spontaneous coronary artery dissection constitutes a rare entity that affects
      mostly women, especially those less than 40 years of age. Treatment of choice is
      a matter of discussion. It is suggested by many that the therapeutic strategy
      should be individualized based on each patient's clinical and angiographic
      manifestations. We present the case of a young woman who underwent surgical
      revascularization for dissection of the left main stem by using both internal
      thoracic arteries. Angiographic follow-up revealed resolution of the dissection,
      obstruction of the right internal thoracic artery graft, and reverse flow in the
      left internal thoracic artery graft.

PMID- 29660361
TI  - Maternal and Fetal Outcome After Cardiac Operations During Pregnancy: A Meta
      Analysis.
AB  - BACKGROUND: In the past, cardiac surgical procedures during pregnancy have been
      associated with a high risk of adverse maternal and fetal outcomes. Therefore,
      this meta-analysis of more recent studies was done to assess the fetomaternal
      risk after cardiac operations during pregnancy using cardiopulmonary bypass.
      METHODS: The MEDLINE, Embase, and Cochrane library were searched to find studies
      from January 1, 1990, to July 31, 2016, without language restriction. We selected
      studies that included at least 4 women to report fetomaternal outcomes after a
      cardiac operation using cardiopulmonary bypass during pregnancy. Two authors
      independently extracted data from the selected studies. The studies were assessed
      for methodological qualities using the Newcastle-Ottawa Scale. The primary
      outcomes included maternal death and any pregnancy loss. The secondary outcomes
      were maternal complications and neonatal complications. Primary analysis
      calculated absolute risks and 95% confidence intervals (CIs) for pregnancy
      outcomes using the DerSimonian-Laird random effects model. Heterogeneity was
      assessed by I2 statistic and visual plot. RESULTS: Ten studies, including 154
      women, were eligible for inclusion in this study. The patients underwent cardiac
      operations during pregnancy involving cardiopulmonary bypass. As calculated per
      100 pregnancies, the pooled unadjusted estimate of maternal mortality was 11.2
      (95% CI, 6.8 to 17.8), pregnancy loss was 33.1 (95% CI, 25.1 to 41.2), maternal
      complications were 8.8 (95% CI, 2.8 to 24.2), and neonatal complications were
      10.8 (95% CI, 4.2 to 25.2). The risks of preterm labor and cesarean delivery were
      28 per 100 pregnancies (95% CI, 15.6 to 45) and 33.8 per 100 pregnancies (95% CI,
      19.1 to 52.4), respectively. CONCLUSIONS: The fetomaternal mortality and
      morbidity after a cardiac operation during pregnancy are higher than that
      reported in the earlier literature (PROSPERO No. CRD42016047093).

PMID- 29660362
TI  - Variability in cerebral blood flow velocity at rest and during mental stress in
      healthy individuals: Associations with cardiovascular parameters and cognitive
      performance.
AB  - This study analyzed variability in cerebral blood flow velocity (CBFV) and
      possible underlying physiological mechanisms during rest and a mental arithmetic
      task. Blood flow velocities were bilaterally recorded by transcranial Doppler
      sonography in the anterior and middle cerebral arteries of 43 participants.
      Electrocardiography, continuous blood pressure (BP) and respiratory recordings
      were additionally obtained. Fast Fourier transformation revealed a spectral
      profile with two main components in CBFV, one in the very low frequency (VLF,
      0.01-0.025 Hz), and the other in the low frequency band (LF, 0.075-0.11 Hz).
      During the task, CBFV variability decreased. While heart rate variability and
      respiration had only weak impacts, BP variability was closely associated with
      CBFV variability. LF CBFV variability correlated negatively with task
      performance. The findings indicate a connection between peripheral and cerebral
      hemodynamics, presumably mediated by the passive pressure-flow relationship and
      neural mechanisms. LF CBFV variability may constitute a suitable marker of mental
      effort load.

PMID- 29660363
TI  - Comparison analysis of microRNAs in response to dengue virus type 2 infection
      between the Vero cell-adapted strain and its source, the clinical C6/36 isolated
      strain.
AB  - To elucidate the differences in microRNAs during dengue virus infection between
      Vero cell-adapted strain (DENV-2-Vero) and its source, the clinical C6/36
      isolated strain (DENV-2-C6/36), a comparison analysis was performed in Vero cells
      by high throughput sequencing. The results showed that the expression of 16 known
      and 3 novel miRNAs exhibited marked differences. 5 known miRNAs were up-regulated
      in DENV-2-C6/36 group, while 11 known microRNAs were down-regulated in DENV-2
      Vero group. The GO enrichment and KEGG pathway analysis showed that there was a
      distinct difference in regulating viral replication between two strains. In DENV
      2-Vero infection group, significantly enriched GO terms included virion
      attachment to host cells, viral structural protein/genome processing and
      packaging. Meanwhile, the regulation of cell death and apoptosis between two
      groups were different in the early stage of infection. KEGG enrichment analysis
      showed that DENV-2-C6/36 infection induced more intense regulation of immune
      related pathways, including Fc gamma R-mediated phagocytosis, etc. DENV-2-Vero
      infection could partially alleviate the immune defense of Vero cells compared
      with DENV-2-C6/36. The results indicated that the distinct microRNA changes
      induced by two DENV-2 strains may be partly related to their infective abilities.
      Our data provide useful insights that help elucidate the host-pathogen
      interactions following DENV infection.

PMID- 29660364
TI  - Silibinin is a direct inhibitor of STAT3.
AB  - We herein combined experimental and computational efforts to delineate the
      mechanism of action through which the flavonolignan silibinin targets STAT3.
      Silibinin reduced IL-6 inducible, constitutive, and acquired feedback activation
      of STAT3 at tyrosine 705 (Y705). Silibinin attenuated the inducible phospho
      activation of Y705 in GFP-STAT3 genetic fusions without drastically altering the
      kinase activity of the STAT3 upstream kinases JAK1 and JAK2. A comparative
      computational study based on docking and molecular dynamics simulation over 14
      different STAT3 inhibitors (STAT3i) predicted that silibinin could directly bind
      with high affinity to both the Src homology-2 (SH2) domain and the DNA-binding
      domain (DBD) of STAT3. Silibinin partially overlapped with the cavity occupied by
      other STAT3i in the SH2 domain to indirectly prevent Y705 phosphorylation, yet
      showing a unique binding mode. Moreover, silibinin was the only STAT3i predicted
      to establish direct interactions with DNA in its targeting to the STAT3 DBD. The
      prevention of STAT3 nuclear translocation, the blockade of the binding of
      activated STAT3 to its consensus DNA sequence, and the suppression of STAT3
      directed transcriptional activity confirmed silibinin as a direct STAT3i. The
      unique characteristics of silibinin as a bimodal SH2- and DBD-targeting STAT3i
      make silibinin a promising lead for designing new, more effective STAT3i.

PMID- 29660366
TI  - Tools and drugs for uracil nucleotide-activated P2Y receptors.
AB  - P2Y receptors (P2YRs) are a family of G protein-coupled receptors activated by
      extracellular nucleotides. Physiological P2YR agonists include purine and
      pyrimidine nucleoside di- and triphosphates, such as ATP, ADP, UTP, UDP,
      nucleotide sugars, and dinucleotides. Eight subtypes exist, P2Y1, P2Y2, P2Y4,
      P2Y6, P2Y11, P2Y12, P2Y13, and P2Y14, which represent current or potential future
      drug targets. Here we provide a comprehensive overview of ligands for the
      subgroup of the P2YR family that is activated by uracil nucleotides: P2Y2 (UTP,
      also ATP and dinucleotides), P2Y4 (UTP), P2Y6 (UDP), and P2Y14 (UDP, UDP-glucose,
      UDP-galactose). The physiological agonists are metabolically unstable due to
      their fast hydrolysis by ectonucleotidases. A number of agonists with increased
      potency, subtype-selectivity and/or enzymatic stability have been developed in
      recent years. Useful P2Y2R agonists include MRS2698 (6-01, highly selective) and
      PSB-1114 (6-05, increased metabolic stability). A potent and selective P2Y2R
      antagonist is AR-C118925 (10-01). For studies of the P2Y4R, MRS4062 (3-15) may be
      used as a selective agonist, while PSB-16133 (10-06) is a selective antagonist.
      Several potent P2Y6R agonists have been developed including 5-methoxyuridine 5'-O
      ((Rp)alpha-boranodiphosphate) (6-12), PSB-0474 (3-11), and MRS2693 (3-26). The
      isocyanate MRS2578 (10-08) is used as a selective P2Y6R antagonist, although its
      reactivity and low water-solubility are limiting. With MRS2905 (6-08), a potent
      and metabolically stable P2Y14R agonist is available, while PPTN (10-14)
      represents a potent and selective P2Y14R antagonist. The radioligand [3H]UDP can
      be used to label P2Y14Rs. In addition, several fluorescent probes have been
      developed. Uracil nucleotide-activated P2YRs show great potential as drug
      targets, especially in inflammation, cancer, cardiovascular and neurodegenerative
      diseases.

PMID- 29660365
TI  - In silico genotoxicity and carcinogenicity prediction for food-relevant secondary
      plant metabolites.
AB  - Humans are exposed to thousands of different secondary plant metabolites which
      may have beneficial health effects, but numerous compounds may also have toxic
      potential. In the present study we have examined the genotoxic and carcinogenic
      potential of 609 food-relevant phytochemicals by using computer models for
      toxicity prediction. We developed a scoring method and combined the results of
      different models to increase the predictive power. A combination of the VEGA
      models SARpy, KNN, ISS, and CAESAR, and of the LAZAR model "Salmonella
      typhimurium" for genotoxicity prediction performed better than the single models
      regarding specificity and accuracy. Statistical evaluation of the combined model
      for carcinogenicity prediction was not possible due to the low number of
      substances suitable for model validation. The in silico results of the present
      exercise will be useful for priority setting purposes regarding future risk
      assessment of secondary plant metabolites. Based on our analysis, (-)
      asimilobine, aloin, annoretine, chrysothrone, coptisine, elymoclavine, and
      thalicminine were predicted to be genotoxic with high probability and may
      therefore be selected for subsequent experimental genotoxicity testing. Moreover,
      the class of pyrrolizidine alkaloids is suggested to be a high priority subject
      for further studies as these substances have been predicted to be carcinogenic
      with high probability.

PMID- 29660367
TI  - Natural killer cells and their therapeutic role in pancreatic cancer: A
      systematic review.
AB  - Pancreatic cancer is among the three deadliest cancers worldwide with the lowest
      5-year survival of all cancers. Despite all efforts, therapeutic improvements
      have barely been made over the last decade. Even recent highly promising targeted
      and immunotherapeutic approaches did not live up to their expectations.
      Therefore, other horizons have to be explored. Natural Killer (NK) cells are
      gaining more and more interest as a highly attractive target for cancer
      immunotherapies, both as pharmaceutical target and for cell therapies. In this
      systematic review we summarise the pathophysiological adaptions of NK cells in
      pancreatic cancer and highlight possible (future) therapeutic NK cell-related
      targets. Furthermore, an extensive overview of recent therapeutic approaches with
      an effect on NK cells is given, including cytokine-based, viro- and
      bacteriotherapy and cell therapy. We also discuss ongoing clinical trials that
      might influence NK cells. In conclusion, although several issues regarding NK
      cells in pancreatic cancer remain unsolved and need further investigation,
      extensive evidence is already provided that support NK cell oriented approaches
      in pancreatic cancer.

PMID- 29660368
TI  - Flow cytometry for receptor analysis from ex-vivo brain tissue in adult rat.
AB  - BACKGROUND: Flow cytometry allows single-cell analysis of peripheral biological
      samples and is useful in many fields of research and clinical applications,
      mainly in hematology, immunology, and oncology. In the neurosciences, the flow
      cytometry separation method was first applied to stem cell extraction from
      healthy or cerebral tumour tissue and was more recently tested in order to
      phenotype brain cells, hippocampal neurogenesis, and to detect prion proteins.
      However, it remains sparsely applied in quantifying membrane receptors in
      relation to synaptic plasticity. NEW METHOD: We aimed to optimize a flow
      cytometric procedure for receptor quantification in neurons and non-neurons. A
      neural dissociation process, myelin separation, fixation, and membrane
      permeability procedures were optimized to maximize cell survival and analysis in
      hippocampal tissue obtained from adult rodents. We then aimed to quantify
      membrane muscarinic acetylcholine receptors (mAChRs) in rats with and without
      bilateral vestibular loss (BVL). RESULTS: mAChR's were quantified for neuronal
      and non-neuronal cells in the hippocampus and striatum following BVL. At day 30
      but not at day 7 following BVL, there was a significant increase (P <= 0.05) in
      the percentage of neurons expressing M2/4 mAChRs in both the hippocampus and the
      striatum. CONCLUSION: Here, we showed that flow cytometry appears to be a
      reliable method of membrane receptor quantification in ex-vivo brain tissue.

PMID- 29660369
TI  - Evaluation of an Epigenetic Assay for Predicting Repeat Prostate Biopsy Outcome
      in African American Men.
AB  - OBJECTIVES: To evaluate an epigenetic assay performed on tissue from negative
      prostate biopsies in a group of African American (AA) men undergoing repeat
      biopsy, and to compare accuracy for predicting repeat biopsy outcome to prior
      studies conducted in predominantly Caucasian populations. METHODS: The study
      population consisted of 211 AA men from seven urology centers across the U.S.,
      all of whom were undergoing 12-core trans-rectal ultrasound guided repeat biopsy
      within 30 months from a negative index biopsy. All biopsy cores from the negative
      index biopsy were profiled for the epigenetic biomarkers GSTP1, APC and RASSF1
      using ConfirmMDx for Prostate Cancer. RESULTS: Upon repeat biopsy, 130/211 (62%)
      subjects had no prostate cancer (PCa) detected and 81/211 (38%) were diagnosed
      with PCa. Of the subjects with PCa, 54/81 (67%) were diagnosed with Gleason Score
      (GS) <= 6 PCa and 27/81 (33%) with GS >=7 disease. For detection of PCa at repeat
      biopsy, ConfirmMDx sensitivity was 74.1% and specificity 60.0%, equivalent to
      prior studies (P=0.235 and 0.697, respectively). For detection of GS >= 7 PCa,
      sensitivity was 78% and specificity 53%. The negative predictive values for
      detection of all PCa and GS >= 7 PCa were 78.8% and 94.2%, respectively.
      CONCLUSIONS: In this group of AA men, we successfully validated an epigenetic
      assay to assess the need for repeat biopsy. Results were consistent with previous
      studies from predominantly Caucasian populations. Therefore, the ConfirmMDx assay
      is a useful tool for risk stratification of AA men who had an initial negative
      biopsy.

PMID- 29660370
TI  - Reply to: "DCD consensus and futility in liver transplantation".

PMID- 29660371
TI  - Capacity limitations to extract the mean emotion from multiple facial expressions
      depend on emotion variance.
AB  - We examined the processing capacity and the role of emotion variance in ensemble
      representation for multiple facial expressions shown concurrently. A standard set
      size manipulation was used, whereby the sets consisted of 4, 8, or 16 morphed
      faces each uniquely varying along a happy-angry continuum (Experiment 1) or a
      neutral-happy/angry continuum (Experiments 2 & 3). Across the three experiments,
      we reduced the amount of emotion variance in the sets to explore the boundaries
      of this process. Participants judged the perceived average emotion from each set
      on a continuous scale. We computed and compared objective and subjective
      difference scores, using the morph units and post-experiment ratings,
      respectively. Results of the subjective scores were more consistent than the
      objective ones across the first two experiments where the variance was relatively
      large, and revealed each time that increasing set size led to a poorer averaging
      ability, suggesting capacity limitations in establishing ensemble representations
      for multiple facial expressions. However, when the emotion variance in the sets
      was reduced in Experiment 3, both subjective and objective scores remained
      unaffected by set size, suggesting that the emotion averaging process was
      unlimited in these conditions. Collectively, these results suggest that
      extracting mean emotion from a set composed of multiple faces depends on both
      structural (attentional) and stimulus-related effects.

PMID- 29660373
TI  - Selenium-regulated hierarchy of human selenoproteome in cancerous and
      immortalized cells lines.
AB  - BACKGROUND: Selenoproteins (25 genes in human) co-translationally incorporate
      selenocysteine using a UGA codon, normally used as a stop signal. The human
      selenoproteome is primarily regulated by selenium bioavailability with a tissue
      specific hierarchy. METHODS: We investigated the hierarchy of selenoprotein
      expression in response to selenium concentration variation in four cell lines
      originating from kidney (HEK293, immortalized), prostate (LNCaP, cancer), skin
      (HaCaT, immortalized) and liver (HepG2, cancer), using complementary analytical
      methods. We performed (i) enzymatic activity, (ii) RT-qPCR, (iii) immuno
      detection, (iv) selenium-specific mass spectrometric detection after non
      radioactive 76Se labeling of selenoproteins, and (v) luciferase-based reporter
      constructs in various cell extracts. RESULTS: We characterized cell-line specific
      alterations of the selenoproteome in response to selenium variation that, in most
      of the cases, resulted from a translational control of gene expression. We
      established that UGA-selenocysteine recoding efficiency, which depends on the
      nature of the SECIS element, dictates the response to selenium variation.
      CONCLUSIONS: We characterized that selenoprotein hierarchy is cell-line specific
      with conserved features. This analysis should be done prior to any experiments in
      a novel cell line. GENERAL SIGNIFICANCE: We reported a strategy based on
      complementary methods to evaluate selenoproteome regulation in human cells in
      culture.

PMID- 29660372
TI  - Heparan sulfate 3-O-sulfotransferase 2 (HS3ST2) displays an unexpected
      subcellular localization in the plasma membrane.
AB  - BACKGROUND: Heparan sulfate (HS) 3-O-sulfation can be catalysed by seven 3-O
      sulfotransferases (HS3STs) in humans, still it is the rarest modification in HS
      and its biological function is yet misunderstood. HS3ST2 and HS3ST3B exhibit the
      same activity in vitro. They are however differently expressed in macrophages
      depending on cell environment, which suggests that they may be involved in
      distinct cellular processes. Here, we hypothesized that both isozymes might also
      display distinct subcellular localizations. METHODS: The subcellular distribution
      of HS3ST2 and HS3ST3B was analysed by using overexpression systems in HeLa cells.
      The localization of endogenous HS3ST2 was confirmed by immunostaining in primary
      macrophages. RESULTS: We found that HS3ST3B was only localized in the Golgi
      apparatus and no difference between full-length enzyme and truncated construct
      depleted of its catalytic domain was observed. In contrast, HS3ST2 was clearly
      visualized at the plasma membrane. Its truncated form remained in the Golgi
      apparatus, meaning that the catalytic domain might support correct addressing of
      HS3ST2 to cell surface. Moreover, we found a partial co-localization of HS3ST2
      with syndecan-2 in HeLa cells and primary macrophages. Silencing the expression
      of this proteoglycan altered the localization of HS3ST2, which suggests that
      syndecan-2 is required to address the isozyme outside of the Golgi apparatus.
      CONCLUSIONS: We demonstrated that HS3ST3B is a Golgi-resident isozyme, while
      HS3ST2 is addressed to the plasma membrane with syndecan-2. GENERAL SIGNIFICANCE:
      The membrane localization of HS3ST2 suggests that this enzyme may participate in
      discrete processes that occur at the cell surface.

PMID- 29660374
TI  - A ternary-complex of a suicide gene, a RAGE-binding peptide, and polyethylenimine
      as a gene delivery system with anti-tumor and anti-angiogenic dual effects in
      glioblastoma.
AB  - The receptor for advanced glycation end-products (RAGE) is involved in tumor
      angiogenesis. Inhibition of RAGE might be an effective anti-angiogenic therapy
      for cancer. In this study, a cationic RAGE-binding peptide (RBP) was produced as
      an antagonist of RAGE, and a ternary-complex consisting of RBP, polyethylenimine
      (2 kDa, PEI2k), and a suicide gene (pHSVtk) was developed as a gene delivery
      system with dual functions: the anti-tumor effect of pHSVtk and anti-angiogenic
      effect of RBP. As an antagonist of RAGE, RBP decreased the secretion of vascular
      endothelial growth factor (VEGF) in activated macrophages and reduced the tube
      formation of endothelial cells in vitro. In in vitro transfection assays, the
      RBP/PEI2k/plasmid DNA (pDNA) ternary-complex had higher transfection efficiency
      than the PEI2k/pDNA binary-complex. In an intracranial glioblastoma animal model,
      the RBP/PEI2k/pHSVtk ternary-complex reduced alpha-smooth muscle actin
      expression, suggesting that the complex has an anti-angiogenic effect. In
      addition, the ternary-complex had higher pHSVtk delivery efficiency than the
      PEI2k/pHSVtk and PEI25k/pHSVtk binary-complexes in an animal model. As a result,
      the ternary-complex induced apoptosis and reduced tumor volume more effectively
      than the PEI2k/pHSVtk and PEI25k/pHSVtk binary-complexes. In conclusion, due to
      its dual anti-tumor and anti-angiogenesis effects, the RBP/PEI2k/pHSVtk ternary
      complex might be an efficient gene delivery system for the treatment of
      glioblastoma.

PMID- 29660375
TI  - The secretome of adipose-derived mesenchymal stem cells protects SH-SY5Y cells
      from arsenic-induced toxicity, independent of a neuron-like differentiation
      mechanism.
AB  - Arsenic exposure through contaminated food, water, and air causes irreversible
      neural damage and affects millions of people worldwide. Several studies have
      demonstrated that the secreted factors (secretome) from mesenchymal stromal/stem
      cells (MSCs) can promote neural recovery after several forms of injury including
      stroke and neurodegenerative diseases. The present study was conducted to
      determine if the secretome from adipose-derived MSCs (ADSCs) prevents arsenic
      damage to SH-SY5Y cells. To this end, human neuroblastoma cells (SH-SY5Y) were
      pre-treated with the secretome from ADSCs and then challenged with different
      concentrations of arsenic. After various doses and exposure times, the extent of
      neuronal injury was assessed using MTT reduction and LDH release assays as well
      as LIVE/DEAD staining. These data demonstrate that the ADSC secretome protects SH
      SY5Y cells from arsenic-induced toxicity. Previous reports have shown that the
      secretome of MSCs can induce neuroblast differentiation and mature neurons are
      less susceptible to chemical-induced toxicity. In the current study,
      proliferation assays, neurite length assessment, and quantitative RT-PCR of
      differentiation markers indicated that the ADSC secretome does not induce SH-SY5Y
      differentiation into a mature neuron-like phenotype. In contrast, our results
      demonstrated that soluble factor(s) in the ADSC secretome enhance SH-SY5Y cell
      substrate-dependent adhesion. The present study is the first to illustrate that
      the secretome from ADSCs protects SH-SY5Y cells from arsenic-induced toxicity.
      Additionally, we showed that protection against arsenic toxicity is not dependent
      on SH-SY5Y cell differentiation into a mature neuron-like phenotype, but involves
      soluble factor(s) in the secretome that appear to enhance cell survival by an
      adhesion-dependent mechanism.

PMID- 29660376
TI  - New insight into isobolographic analysis for combinations of a full and partial
      agonist: Curved isoboles.
AB  - Receptor ligands in mixtures may produce effects that are greater than the effect
      predicted from their individual dose-response curves. The historical basis for
      predicting the mixture effect is based on Loewe's concept and its mathematical
      formulation. This concept considers compounds with constant relative potencies
      (parallel dose-response curves) and leads to linear additive isoboles. These
      lines serve as references for distinguishing additive from nonadditive
      interactions according to the positions of the experimental data on or outside of
      the lines. In this paper, we applied a highly relevant two-state model for a
      description of the receptor-ligand interaction in the construction of the
      isobologram. In our model we consider partial agonists that have dose-response
      curve slopes differing from one. With this theoretical basis, we demonstrated
      that a combination of compounds with different efficacies leads to curved
      isoboles. This model should overwrite Tallarida's flawed assumption about
      isobolographic analysis of partial agonists and enhance our understanding of how
      the partial agonists contribute to the overall mixture effect.

PMID- 29660377
TI  - Apathy following traumatic brain injury: A review.
AB  - Apathy is a common problem after traumatic brain injury (TBI) and can have a
      major impact on cognitive function, psychosocial outcome and engagement in
      rehabilitation. For scientists and clinicians it remains one of the least
      understood aspects of brain-behaviour relationships encompassing disturbances of
      cognition, motivation, emotion and action, and is variously an indication of
      organic brain disease or psychiatric disorder. Apathy can be both sign and
      symptom and has been proposed as a diagnosis in its own right as well as a
      secondary feature of other conditions. This review considers previous approaches
      to apathy in terms of relevant psychological constructs and those neural
      counterparts most likely to be implicated after TBI. Neurobehavioural disorders
      of apathy are characterised chiefly by dysfunction of executive control of goal
      oriented behaviour or the neural substrates of reward-based and emotional
      learning. We argue that it is possible to distinguish a primary disorder of
      apathy as an organic neurobehavioural state from secondary presentations due to
      an impoverished environment or psychological disturbance which has implications
      for treatment.

PMID- 29660378
TI  - An epi(c)genetic war: Pathogens, cancer and human genome.
AB  - Cancer is characterized by inter- and intra-tumor heterogeneity and this is also
      observed in the context of cancers caused by pathogens. Nearly 20% of all cancers
      are attributable to pathogenic organisms. Pathogenic infections result in
      deregulation of gene expression both by genetic and epigenetic mechanisms,
      thereby causing malignant transformation. Another characteristic of pathogen
      induced cancers is the occurrence of chronic inflammation due to activation of
      the innate and adaptive arms of the immune system. This review focuses on the
      epigenetic changes induced by oncoviruses, parasites, cancer-causing bacteria and
      'endogenous pathogens' to trigger host cell proliferation indefinitely as well as
      the inflammation associated with pathogen-induced cancers. The opportunity of
      targeting components of both pathogen and host epigenetic machinery to limit
      tumor progression is also discussed.

PMID- 29660379
TI  - Nervous system and primary liver cancer.
AB  - Recent advances have found irregular activities of the nervous system-associated
      factors in the development and progression of primary liver cancer. These factors
      contributed in the regulation of migration, proliferation, and apoptosis of
      cancer cells, and took a role in modulating invasion, metastasis, and recurrence
      after curative treatment. In clinical researches, neural-related factors were
      found to be significant prognostic factors, suggesting that the interactions
      between nervous system and primary liver cancer are indispensable in
      understanding underlying biological mechanisms. Herein, we reviewed up-to-date
      achievements in this area and the future perspectives of the interactions between
      the nervous system and primary liver cancer.

PMID- 29660380
TI  - Jade family PHD finger 3 (JADE3) increases cancer stem cell-like properties and
      tumorigenicity in colon cancer.
AB  - Jade family PHD finger 3 (JADE3) plays a role in inducing histone acetylation
      during transcription, and is involved in the progression of several human
      cancers; however, its role in colon cancer remains unclear. Herein, we found that
      JADE3 was markedly upregulated in colon cancer tissues and significantly
      correlated with cancer progression, and predicted shorter patient survival.
      Further, JADE3 was expressed much higher in colon cancer cell lines that are
      enriched with a stem-like signature. Overexpression of JADE3 increased, while
      silencing JADE3 reduced cancer stem cell-like traits in colon cancer cells in
      vitro and in vivo. Importantly, silencing of JADE3 strongly impaired the tumor
      initiating capacity of colon cancer cells in vivo. Furthermore, JADE3 interacted
      with the promoters of colon stem cell marker LGR5 and activated its
      transcription, by increasing the occupancy of p300 acetyltransferase and histone
      acetylation on the promoters. Finally, we found that JADE3 expression was
      substantially induced by Wnt/beta-catenin signaling. These findings suggest an
      oncogenic role of JADE3 by regulating cancer stem cell-like traits in the colon
      cancer, and therefore JADE3 might be a potential therapeutic target for the
      treatment of colon cancer.

PMID- 29660381
TI  - ARID1A ablation leads to multiple drug resistance in ovarian cancer via
      transcriptional activation of MRP2.
AB  - Multiple Drug Resistance (MDR) of ovarian cancer is a severe trouble for clinical
      treatment and always contributes to a bad prognosis. AT-rich interaction domain 1
      A (ARID1A) has been recognized as a bona fide tumor suppressor gene in recent
      years, with the highest mutation rate in ovarian cancer. Previous study
      illustrated that ARID1A expression is negatively correlated with chemoresistance
      of ovarian cancer cases. However, the specific role of ARID1A in chemoresistance
      of ovarian cancer remains elusive. In this study, we showed that ARID1A knockdown
      in ovarian cancer cells significantly reduced their apoptosis rate and led to
      MDR, while ectopic expression of ARID1A showed opposite effects. ARID1A depletion
      transcriptionally activates the expression of multidrug resistance-associated
      protein 2 (MRP2) following chromatin remodeling. Furthermore, IHC analysis of
      ovarian cancer samples confirmed that ARID1A expression was strong negatively
      correlated with MRP2 expression. Both ARID1A and MRP2 expression levels are
      correlated with sensitivity to platinum. Collectively, our results illustrated
      that ARID1A loss in ovarian cancer leads to MDR through upregulation of MRP2,
      providing an opportunity to overcome the ARID1A loss induced chemoresistance of
      ovarian cancer by targeting MRP2.

PMID- 29660382
TI  - Elevated plasma soluble (pro)renin receptor levels are associated with left
      ventricular remodeling and renal function in chronic heart failure patients with
      reduced ejection fraction.
AB  - Soluble (pro)renin receptor [s(P)RR], which is generated from cleavage of (P)RR,
      can be detected in plasma and urine. s(P)RR levels can reflect the severity of
      some diseases, such as renal lesions, gestational diabetes mellitus or
      hypertension, and obstructive sleep apnea syndrome. However, the relationship
      between s(P)RR levels and the severity of chronic heart failure remains
      undetermined. We studied s(P)RR levels in 118 patients with chronic heart failure
      with reduced ejection fraction (HFrEF), including 86 without renal dysfunction
      (HF) and 32 with renal dysfunction (HF + RF), and 28 healthy subjects (HS) to
      reveal the relationship between s(P)RR levels and other HFrEF parameters. Plasma
      s(P)RR levels were 22.2 +/- 4.1 ng/mL (HS), 26.4 +/- 5.3 ng/ mL (HF) and 30.0 +/-
      5.3 ng/mL (HF + RF). Plasma s(P)RR levels were significantly higher in the HF
      group than in the HS group (P < 0.001) and even more increased in the HF + RF
      group (P < 0.001 vs. the HS group and P < 0.05 vs. the HF group). Multivariate
      regression analysis revealed that the left ventricular mass index (LVMI) and
      estimated glomerular filtration rate (eGFR) were independently related to s(P)RR
      levels in HFrEF patients. In conclusion, high plasma s(P)RR levels are associated
      with left ventricular remodeling and, especially, with renal dysfunction.
      Therefore, s(P)RR is a promising evaluative indicator for the severity of HFrEF
      patients.

PMID- 29660383
TI  - Dosage form modification and oral drug delivery in older people.
AB  - Many people cannot swallow whole tablets and capsules. The cause ranges from
      difficulties overriding the natural instinct to chew solids/foodstuff before
      swallowing, to a complex disorder of swallowing function affecting the ability to
      manage all food and fluid intake. Older people can experience swallowing
      difficulties because of co-morbidities, age-related physiological changes, and
      polypharmacy. To make medicines easier to swallow, many people will modify the
      medication dosage form e.g. split or crush tablets, and open capsules. Some of
      the challenges associated with administering medicines to older people, and
      issues with dosage form modification will be reviewed. Novel dosage forms in
      development are promising and may help overcome some of the issues. However,
      until these are more readily available, effective interdisciplinary teams, and
      improving patient health literacy will help reduce the risk of medication
      misadventures in older people.

PMID- 29660384
TI  - Development of a recombinant sigmaB protein based dot-ELISA for the diagnosis of
      avian reovirus (ARV).
AB  - Avian reovirus (ARV) causes significant economic losses to the poultry industry
      worldwide. The ARV proteins fall into three different classes based on their
      sizes:lambda (large); MU (medium) and sigma (small). sigmaB, an outer capsid
      protein of the ARV contains group specific neutralizing epitopes and induces
      strong immune response in naturally infected chickens. This study describes the
      development of a rapid dot-enzyme linked immunosorbent assay (dot-ELISA) using
      recombinant sigmaB protein antigen of 54 kDa (approx). The assay is rapid (4-5 h)
      and results can be read by the naked eye. Sixteen ARV positive serum samples
      (group A) produced strong reaction in the dot-ELISA while twenty of the ARV
      negative serum samples (group B) collected from SPF chickens showed no reaction.
      Seventy six randomly collected serum samples were tested with a commercial
      indirect ELISA kit and the in-house developed dot-ELISA. A total of sixty eight
      serum samples were found to be positive by indirect ELISA and sixty five serum
      samples were found to be positive by dot-ELISA. Therefore, using the commercial
      ELISA as the reference test, the dot-ELISA had a diagnostic sensitivity of 83.8%
      and specificity of 88.6%. This dot-ELISA can be used as a simple, reliable and
      inexpensive alternative to commercial ELISA kits for serodiagnosis of ARV where
      the facilities for standard ELISA are not available.

PMID- 29660385
TI  - Pre-operative asymptomatic bacteriuria: a risk factor for prosthetic joint
      infection?
AB  - BACKGROUND: Infection is a rare complication following implantation of prosthetic
      material into a joint. The impact of asymptomatic bacteriuria (ASB) before
      elective operations and the subsequent risk of prosthetic joint infection (PJI)
      are not well understood. AIMS: To assess the prevalence of ASB amongst patients
      undergoing total arthroplasty of the hip and knee; and to determine the rates of
      PJI diagnosed within two years of the arthroplasty and if ASB is an independent
      risk factor for developing PJI. METHODS: Patients who had total/unicondylar knee
      or total hip arthroplasty were reviewed retrospectively over a five-year period.
      Pre-operative urine samples within one year of surgery were analysed, and those
      with ASB were identified. The primary outcome was PJI within the first
      postoperative year. FINDINGS: In total, 5542 patients were included. Of these,
      4368 had a pre-operative urine culture recorded. The prevalence of ASB was 140 of
      4368 (3.2%). The overall PJI rate was 56 of 5542 (1.01%). Of those with PJI, 33
      had a pre-operative urine sample recorded. The infection rates were 5% (seven of
      140) in the ASB group, 0.61% (26 of 4228) in the no-ASB group and 1.96% (23 of
      1174) in the group without a urine sample (P < 0.001). The ASB isolate was the
      same micro-organism as the PJI isolate in one of the seven cases. CONCLUSION: The
      association between ASB and PJI is statistically significant, but the urine
      isolates did not relate to the isolates in the prosthetic joint, suggesting that
      the relationship is unlikely to be causal.

PMID- 29660386
TI  - Long-term cryopreservation of non-spore-forming fungi in MicrobankTM beads for
      plant pathological investigations.
AB  - Long-term preservation of experimental fungi without genetic, morphological, and
      pathogenic changes is of paramount importance in mycological and plant
      pathological investigations. Several cryogenic and non-cryogenic methods are
      available for the preservation of fungi, but the methods can be cumbersome,
      hazardous, expensive, and often not suitable for long-term storage of non-spore
      forming (sterile) fungi. A method of preservation of spore-forming fungi in
      commercially available porous beads (MicrbankTM) under cryogenic condition was
      successfully tested for three non-spore-forming basidiomycetes genera:
      Rhizoctonia solani (teleomorph: Thanatephorus cucumeris) (n = 19), Ceratobasidium
      species (n = 1), and Waitea circinata (n = 3), and a non-spore forming
      ascomycetes, Sclerotinia sclerotiorum (n = 1). For comparison, spore-forming
      ascomycetous fungi, Alternaria alternata (n = 1), Bauveria basiana (n = 2),
      Botrytis cinerea (n = 1), Fusarium oxysporum f.sp. gladiolii (n = 1), Trichoderma
      spp. (n = 3), and Thielaviopsis basicola (n = 2) were also cryopreserved in
      Microbank beads. Viable fungal isolates of all test species were retrieved after
      five years of storage at -80  degrees C, which was longer than the viabilities of
      the corresponding isolates cryopreserved in agar plugs or colonized wheat seeds.
      Fungi revived from the Microbank beads maintained identical morphology and
      cultural characteristics of the parent isolates. Randomly selected Rhizoctonia
      isolates revived from the Microbank beads maintained respective pathological
      properties of the parent isolates; also, no mutation was detected in the internal
      transcribed spacer (ITS) ribosomal DNA when compared with respective cultures
      maintained at ambient temperature. This finding demonstrated the utility of
      cryopreservation in Microbank beads as a convenient alternative to conventional
      long-term preservation of a wide group of fungal cultures for plant pathological
      investigations and serves as the first report of using porous beads under
      cryogenic conditions for long-term storage of sterile fungi.

PMID- 29660387
TI  - Long-term inhibition of PDE5 ameliorates aging-induced changes in rat testis.
AB  - NO-cGMP signaling pathway has been implicated in reduction of testicular
      steroidogenesis during aging. Here we analyzed the effect of PDE5 inhibition on
      old testicular phenotype formation. The old phenotype exhibited low testosterone
      and increased nitrite levels in circulation, increased cGMP accumulation in
      testicular interstitial fluid (TIF), progressive atrophy of testicular
      seminiferous tubules and enlargement of interstitial area followed by rise in
      blood vessel density and slight increase in the number of Leydig cells and
      macrophages. Leydig cells have reduced steroidogenic capacity, increased MAP
      kinases expression (MEK, ERK1/2, JNK) and antiapoptotic PRKG1 and AKT, suggesting
      increased proliferation/survival and accumulation of senescent Leydig cells in
      testis. In 12 month-old rats, a long-term treatment with sildenafil (PDE5
      inhibitor) normalized testosterone/nitrite levels in circulation and cGMP
      accumulation in TIF; improved Leydig cell steroidogenic capacity; decreased MEK,
      ERK1/2 and PRKG1 expression; prevented an increase in the Leydig cells number and
      atrophy of seminiferous tubules leading to histological appearance of young rat
      testes. In 18 month-old rats, long-term PDE5 inhibition partially recovered
      testosterone and nitrite levels in serum; normalized PRKG1 expression without
      effect on MEK and ERK1/2; and slowed down Leydig cell and macrophage accumulation
      and regressive tubular changes. Culturing of primary Leydig cells from aged rats
      in presence of PDE5-inhibitor stimulated steroidogenic and MAPK gene expression.
      Taking together, results indicate that cGMP targeting alter both steroidogenesis
      and signaling pathways associated with cell proliferation/survival. The long-term
      PDE5 inhibition improves testicular steroidogenesis and slows-down regressive
      changes in testes during aging.

PMID- 29660389
TI  - Shooting Free Throws Blindfolded (Invited Commentary).

PMID- 29660388
TI  - Outcomes of Gracilis Muscle Flaps in the Management of Groin Complications after
      Arterial Bypass with Prosthetic Graft.
AB  - BACKGROUND: This study details 2-year outcomes of a modified gracilis muscle flap
      (GMF) technique in providing tissue coverage for groin complications after
      arterial bypass surgery with synthetic graft. METHODS: All patients who developed
      groin infections after lower extremity arterial bypass with synthetic graft who
      underwent a GMF technique were included from June 2014 to March 2017 from a
      prospectively collected, purpose-built institutional database. Modifications to
      the standard technique included identification of the muscle using ultrasound to
      ensure precise skip incisions, preservation of the segmental blood supply,
      widening of the tunnel through which the muscle is retroflexed, placement of a
      wound vacuum-assisted closure for healing, and lifelong antibiotics.
      Demographics, laboratory values, bypass procedure, length of stay (LOS),
      disposition, and 1-, 3-, 6-, 12-, and 24-month follow-up data were collected.
      Analysis was performed via descriptive statistics. RESULTS: Over the 3-year study
      period, 22 patients underwent GMF after complications resulted from arterial
      bypass surgery. Types of bypass included aortobifemoral (32%), axillobifemoral
      (14%), femoral-femoral (23%), femoral-popliteal or mixed distal (27%), and thigh
      graft for dialysis (4%). Forty-five percentage of patients presented with graft
      infection, 50% with wound dehiscence, and 5% with graft disruption and bleeding.
      Only 23% of patients were candidates for sartorius muscle flap at the time of
      their initial procedure. The average case length was 64 + 19 min. Sixty-four
      percentage of patients were discharged home with home health care and the
      remainder to a skilled nursing facility. The average LOS was 6.1 + 3.4 days.
      Fifty-four percentages of wounds were healed at 1 month and 100% at 3 months with
      adjunctive vacuum-assisted closure therapy and lifelong antibiotics. Sixty
      percentage of patients were still alive at 24 months, with 33% of grafts still
      patent at that time. Median survival was 18.1 months, and median graft patency
      was 17.9 months. CONCLUSIONS: GMF is a safe and effective treatment for groin
      complications after arterial bypass surgery with synthetic graft. Owing to its
      versatility, area of coverage, ease of use, and durability, it potentially should
      be considered as a primary form of muscle coverage for groin complications.

PMID- 29660391
TI  - Surgical outcomes following rectus muscle plication versus resection combined
      with antagonist muscle recession for basic horizontal strabismus.

PMID- 29660390
TI  - Review of embryo-fetal developmental toxicity studies performed for
      pharmaceuticals approved by FDA in 2016 and 2017.
AB  - Details of embryo-fetal development (EFD) studies were compiled for all FDA drug
      approvals in 2016-17. Rats and rabbits were used for 63% of small molecule (SM)
      drugs. The cynomolgus monkey was used for 47% of biopharmaceuticals. Rodent
      studies using the clinical mAb or animal homologue replaced monkey studies under
      some circumstances. EFD studies were not required for anti-cancer drugs when the
      mode of action was associated with known developmental risk. One quarter of SM
      non-oncology drugs and all tested SM anti-cancer drugs were teratogenic in at
      least one species. The rat and rabbit were essentially equally sensitive to
      developmental toxicity. Eighty-nine percent of SM non-cancer drugs induced
      maternal or fetal toxicity in at least one species at below 25-times human
      exposure (proposed maximum exposure in the draft revised ICH S5(R3) guideline).
      The pregnancy and lactation labeling rule (PLLR) has brought consistency to the
      presentation of EFD data in drug labels.

PMID- 29660392
TI  - Prevalence of uncorrected refractive errors among school-age children in the
      School District of Philadelphia.
AB  - PURPOSE: To determine the prevalence and severity of uncorrected refractive
      errors in school-age children attending Philadelphia public schools. METHODS: The
      Wills Eye Vision Screening Program for Children is a community-based pediatric
      vision screening program designed to detect and correct refractive errors and
      refer those with nonrefractive eye diseases for examination by a pediatric
      ophthalmologist. Between January 2014 and June 2016 the program screened 18,974
      children in grades K-5 in Philadelphia public schools. Children who failed the
      vision screening were further examined by an on-site ophthalmologist or
      optometrist; children whose decreased visual acuity was not amenable to spectacle
      correction were referred to a pediatric ophthalmologist. RESULTS: Of the 18,974
      children screened, 2,492 (13.1%) exhibited uncorrected refractive errors: 1,776
      (9.4%) children had myopia, 459 (2.4%) had hyperopia, 1,484 (7.8%) had
      astigmatism, and 846 (4.5%) had anisometropia. Of the 2,492 with uncorrected
      refractive error, 368 children (14.8%) had more than one refractive error
      diagnosis. In stratifying refractive error diagnoses by severity, mild myopia
      (spherical equivalent of -0.50 D to < -3.00 D) was the most common diagnosis,
      present in 1,573 (8.3%) children. CONCLUSIONS: In this urban population 13.1% of
      school-age children exhibited uncorrected refractive errors. Blurred vision may
      create challenges for students in the classroom; school-based vision screening
      programs can provide an avenue to identify and correct refractive errors.

PMID- 29660393
TI  - Survivin is high in retinoblastoma, but what lies beneath?

PMID- 29660394
TI  - Reply.

PMID- 29660395
TI  - Endogenous PGI2 signaling through IP inhibits neutrophilic lung inflammation in
      LPS-induced acute lung injury mice model.
AB  - Endogenous prostaglandin I2 (PGI2) has inhibitory effects on immune responses
      against pathogens or allergens; however, the immunomodulatory activity of
      endogenous PGI2 signaling in endotoxin-induced inflammation is unknown. To test
      the hypothesis that endogenous PGI2 down-regulates endotoxin-induced lung
      inflammation, C57BL/6 wild type (WT) and PGI2 receptor (IP) KO mice were
      challenged intranasally with LPS. Urine 6-keto-PGF1alpha, a stable metabolite of
      PGI2, was significantly increased following the LPS-challenge, suggesting that
      endogenous PGI2 signaling modulates the host response to LPS-challenge. IPKO mice
      had a significant increase in neutrophils in the BAL fluid as well as increased
      proteins of KC, LIX, and TNF-alpha in lung homogenates compared with WT mice. In
      contrast, IL-10 was decreased in LPS-challenged IPKO mice compared with WT mice.
      The PGI2 analog cicaprost significantly decreased LPS-induced KC, and TNF-alpha,
      but increased IL-10 and AREG in bone marrow-derived dendritic cells (BMDCs) and
      bone marrow-derived macrophages (BMMs) compared with vehicle-treatment. These
      results indicated that endogenous PGI2 signaling attenuated neutrophilic lung
      inflammation through the reduced inflammatory cytokine and chemokine and enhanced
      IL-10.

PMID- 29660396
TI  - Analysis of clinical management of infected breast implants and of factors
      associated to successful breast pocket salvage in infections occurring after
      breast reconstruction.
AB  - OBJECTIVES: Considerable efforts have been devoted so far to improve salvage
      procedures of infected breast implants in absence of defined guidelines or
      validated clinical protocols. Within a cohort of prospectively recruited patients
      who underwent breast reconstruction, we performed a retrospective review of
      proven implant infections in order to describe factors contributing to management
      success. METHODS: We collected data in 1293 consecutive patients who underwent
      two stage (expander+prosthesis) breast reconstruction with at least 12 months of
      follow-up. Demographic data, timing of infection, type of microorganism, intent
      of salvage, fate of the implant, type of antibiotic treatment and follow-up were
      recorded in a prospective data collection on clinical records. RESULTS: Implant
      infections occurred in 103 of 1293 patients (8%). Among these, 73 (71%) were
      proven infections with confirmed microbiology. Implant pocket salvage was
      attempted in 43/73 (59%). patients A higher proportion of expander implant
      pockets were successfully saved compared to prosthetic pocket (p=0,04). Gram
      positive microrganisms represented the majority of etiologic agents, with
      coagulase negative staphylococci prevailing over Staphylococcus aureus. No
      association was observed between success rate and type of infecting
      microorganism. A higher proportion of patients with previous or intraoperative
      radiotherapy or with perioperative chemotherapy underwent an attempt of implant
      salvage (p=0,081 and 0,0571 trend, respectively). No single antibiotic regimen
      was superior to the others in terms of success rate. Implant pocket salvage was
      higher in expanders compared to prostheses (74% vs 33% p=0,04). Higher success
      rates in implant pocket salvage were evident when implant replacement was
      preceded and followed by antibiotic treatment compared to inpatient antibiotic
      treatment alone (100% versus 57%, p=0,035). CONCLUSION: Patient selection in
      clinical practice leads to differences in patients with breast implant infection
      who are considered for attempts at implant salvage vs. those who are treated with
      implant removal. Salvage of breast implant pockets can be obtained in the
      majority of patients with combined one-step implant replacement surgery and
      antibiotic treatment. Increased efforts and protocols to recruit patients into
      pocket salvage management are needed.

PMID- 29660397
TI  - A pharmacology guided approach for setting limits on product-related impurities
      for bispecific antibody manufacturing.
AB  - INTRODUCTION: bFKB1 is a humanized bispecific IgG1 antibody, created by
      conjoining an anti-Fibroblast Growth Factor Receptor 1 (FGFR1) half-antibody to
      an anti-Klothobeta (KLB) half-antibody, using the knobs-into-holes strategy.
      bFKB1 acts as a highly selective agonist for the FGFR1/KLB receptor complex and
      is intended to ameliorate obesity-associated metabolic defects by mimicking the
      activity of the hormone FGF21. An important aspect of the biologics product
      manufacturing process is to establish meaningful product specifications regarding
      the tolerable levels of impurities that copurify with the drug product. The aim
      of the current study was to determine acceptable levels of product-related
      impurities for bFKB1. METHODS: To determine the tolerable levels of these
      impurities, we dosed obese mice with bFKB1 enriched with various levels of either
      HMW impurities or anti-FGFR1-related impurities, and measured biomarkers for KLB
      independent FGFR1 signaling. RESULTS: Here, we show that product-related
      impurities of bFKB1, in particular, high molecular weight (HMW) impurities and
      anti-FGFR1-related impurities, when purposefully enriched, stimulate FGFR1 in a
      KLB-independent manner. By taking this approach, the tolerable levels of product
      related impurities were successfully determined. DISCUSSION: Our study
      demonstrates a general pharmacology-guided approach to setting a product
      specification for a bispecific antibody whose homomultimer-related impurities
      could lead to undesired biological effects.

PMID- 29660398
TI  - Molecular phenotypes of the human kidney: Myoid stromal cells/telocytes and
      myoepithelial cells.
AB  - The connective stromal and epithelial compartments of the kidney have
      regenerative potential and phenotypic flexibility. A few studies have shown that
      cells appertaining to both compartments can exhibit myoid phenotypes. The purpose
      of our study was to investigate the myoid pattern of kidney and its association
      with the kidney niches containing stromal cells/telocytes (SC/TCs). We performed
      an immunohistochemical study using a panel of endothelial, myoid, mesenchymal and
      stem/progenitor markers, namely CD31, CD34, CD105 (endoglin), CD117/c-kit,
      nestin, desmin, alpha-smooth muscle actin (alpha-SMA) and the heavy chain of
      smooth muscle myosin (SMM). We used histologically normal kidney samples,
      obtained after nephrectomy, from nine adult patients. The capsular SC/TCs had a
      strong CD34 and partial nestin and CD105 immunopositivity. Subcapsular and
      interstitial SC/TCs expressed c-kit, nestin, CD105, but also alpha-SMA and SMM,
      therefore having a myoid phenotype. The endothelial SC/TCs phenotype was
      CD31+/CD34+/CD105+/nestin+/-/SMM+/-/alpha-SMA+/-. All three myoid markers were
      expressed in periendothelial SC/TCs. We also found a scarce expression of nestin
      in parietal epithelial cells of Bowman's capsule, and in podocytes. In epithelial
      cells, we found a positive expression for CD31, CD117/c-kit, desmin, CD34, SMM,
      and CD105. In epithelial tubular cells, we found a predominant basal expression
      of the myoid markers (SMM and desmin). In conclusion, myoepithelial tubular
      cells, myoid endothelial cells and myoid SC/TCs are normal constituents of the
      kidney.

PMID- 29660399
TI  - CacyBP/SIP, a Hsp90 binding chaperone, in cellular stress response.
AB  - CacyBP/SIP interacts with Hsp90 and is able to protect proteins from denaturation
      and/or aggregation induced by elevated temperature. In this work we studied the
      influence of different stress factors on CacyBP/SIP level in HEp-2 cells. We have
      found that H2O2 and radicicol treatment resulted in a significant increase (up to
      40%) in the CacyBP/SIP level. We have also found that HEp-2 cells overexpressing
      CacyBP/SIP were more resistant to stress-induced death. Further studies have
      revealed that the Hsf1 transcription factor binds to the CacyBP/SIP gene promoter
      and up-regulates CacyBP/SIP expression under stress conditions. To check whether
      the CacyBP/SIP protein might play a role in stress responses in vivo, we analyzed
      its level in selected brain structures of control and stressed mice. We have
      found that the level of the CacyBP/SIP protein was higher in the
      thalamus/hypothalamus, hippocampus and brainstem of stressed mice. Thus, the
      presented results clearly indicate that CacyBP/SIP is involved in cellular stress
      response.

PMID- 29660400
TI  - Hippocampal coupling with cortical and subcortical structures in the context of
      memory consolidation.
AB  - Memory consolidation is a gradual process through which episodic memories become
      incorporated into long-term 'semantic' representations. It likely involves
      reactivation of neural activity encoding the recent experience during non-REM
      sleep. A critical prerequisite for memory consolidation is precise coordination
      of reactivation events between the hippocampus and cortical/subcortical
      structures, facilitated by the coupling of local field potential (LFP)
      oscillations (slow oscillations, sleep spindles and sharp wave/ripples) between
      these structures. We review the rapidly expanding literature on the qualitative
      and quantitative aspects of hippocampal oscillatory and neuronal coupling with
      cortical/subcortical structures in the context of memory reactivation.
      Reactivation in the hippocampus and cortical/subcortical structures is tightly
      coupled with sharp wave/ripples. Hippocampal-cortical/subcortical coupling is
      rich in dimensionality and this dimensionality is likely underestimated due to
      the limitations of the current methodology.

PMID- 29660401
TI  - Intravenous fosfomycin for pulmonary exacerbation of cystic fibrosis: Real life
      experience of a large adult CF centre.
AB  - BACKGROUND: The increased prevalence of multi-drug resistant strains of
      P.aeruginosa and allergic reactions among adult patients with cystic fibrosis
      (CF) limits the number of antibiotics available to treat pulmonary exacerbations.
      Fosfomycin, a unique broad spectrum bactericidal antibiotic, might offer an
      alternative therapeutic option in such cases. AIM: To describe the clinical
      efficacy, safety and tolerability of intravenous fosfomycin in combination with a
      second anti-pseudomonal antibiotic to treat pulmonary exacerbations in adult
      patients with CF. METHOD: A retrospective analysis of data captured
      prospectively, over a 2-years period, on the Unit electronic medical records for
      patients who received IV fosfomycin was performed. Baseline characteristics in
      the 12 months prior treatment, lung function, CRP, renal and liver function and
      electrolytes at start and end of treatment were retrieved. RESULTS: 54 patients
      received 128 courses of IV fosfomycin in combination with a second antibiotic,
      resulting in improved FEV1 (0.94 L vs 1.24 L, p < 0.01) and reduced CRP (65 mg/L
      vs 19.3 mg/L, p < 0.01). Renal function pre- and post-treatment remained stable.
      4% (n = 5) of courses were complicated with AKI at mid treatment, which resolved
      at the end of the course. Electrolyte supplementation was required in 18% of
      cases for potassium and magnesium and 7% for phosphate. Nausea was the most
      common side effect (48%), but was well controlled with anti-emetics. CONCLUSION:
      Antibiotic regimens including fosfomycin appear to be clinically effective and
      safe. Fosfomycin should, therefore, be considered as an add-on therapy in
      patients who failed to respond to initial treatment and with multiple drug
      allergies.

PMID- 29660402
TI  - Lead (Pb) induced ATM-dependent mitophagy via PINK1/Parkin pathway.
AB  - Lead (Pb), a widely distributed environmental pollutant, is known to induce
      mitochondrial damage as well as autophagy in vitro and in vivo. In this study, we
      found that Pb could trigger mitophagy in both HEK293 cells and the kidney cortex
      of male Kunming mice. However, whether ataxia telangiectasis mutated (ATM) which
      is reported to be linked with PTEN-induced putative kinase 1 (PINK1)/Parkin
      pathway (a well-characterized mitophagic pathway) participates in the regulation
      of Pb-induced mitophagy and its exact role remains enigmatic. Our results
      indicated that Pb activated ATM in vitro and in vivo, and further in vitro
      studies showed that ATM could co-localize with PINK1 and Parkin in cytosol and
      interact with PINK1. Knockdown of ATM by siRNA blocked Pb-induced mitophagy even
      under the circumstance of enhanced accumulation of PINK1 and mitochondrial
      Parkin. Intriguingly, elevation instead of reduction in phosphorylation level of
      PINK1 and Parkin was observed in response to ATM knockdown and Pb did not
      contribute to the further increase of their phosphorylation level, implying that
      ATM indirectly regulated PINK1/Parkin pathway. These findings reveal a novel
      mechanism for Pb toxicity and suggest the regulatory importance of ATM in
      PINK1/Parkin-mediated mitophagy.

PMID- 29660403
TI  - ROS modifiers and NOX4 affect the expression of the survivin-associated radio
      adaptive response.
AB  - The survivin-associated radio-adaptive response can be induced following exposure
      to ionizing radiation in the dose range from 5 to 100 mGy, and its magnitude of
      expression is dependent upon the TP53 mutational status of cells and ROS
      signaling. The purpose of the study was to investigate the potential role of ROS
      in the development of the survivin-associated adaptive response. Utilizing human
      colon carcinoma HCT116 TP53 wild type (WT) and HCT116 isogenic TP53 null mutant
      (Mut) cell cultures, the roles of inter- and intracellular ROS signaling on
      expression of the adaptive response as evidenced by changes in intracellular
      translocation of survivin measured by ELISA, and cell survival determined by a
      standard colony forming assay were investigated using ROS modifying agents that
      include emodin, N-acetyl-L-cysteine (NAC), fulvene-5, honokiol, metformin and
      rotenone. The role of NADPH oxidase 4 (NOX4) in the survivin-associated adaptive
      response was investigated by transfecting HCT116 cells, both WT and Mut, with two
      different NOX4 siRNA oligomers and Western blotting. A dose of 5 mGy or a 15 min
      exposure to 50 uM of the ROS producing drug emodin were equally effective in
      inducing a pro-survival adaptive response in TP53 WT and a radio-sensitization
      adaptive response in TP53 Mut HCT116 cells. Each response was associated with a
      corresponding translocation of survivin into the cytoplasm or nucleus,
      respectively. Exposure to 10 mM NAC completely inhibited both responses. Exposure
      to 10 uM honokiol induced responses similar to those observed following NAC
      exposure in TP53 WT and Mut cells. The mitochondrial complex 1 inhibitor rotenone
      was effective in reducing both cytoplasmic and nuclear survivin levels, but was
      ineffective in altering the expression of the adaptive response in either TP53 WT
      or Mut cells. In contrast, both metformin and fulvene-5, inhibitors of NOX4,
      facilitated the reversal of TP53 WT and Mut adaptive responses from pro-survival
      to radio-sensitization and vice versa, respectively. These changes were
      accompanied by corresponding reversals in the translocation of survivin to the
      nuclei of TP53 WT and to the cytoplasm of TP53 Mut cells. The potential role of
      NOX4 in the expression of the survivin-associated adaptive response was
      investigated by transfecting HCT116 cells with NOX4 siRNA oligomers to inhibit
      NOX4 expression. Under these conditions NOX4 expression was inhibited by about
      50%, resulting in a reversal in the expression of the TP53 WT and Mut survivin
      associated adaptive responses as was observed following metformin and fulvene-5
      treatment. Exposure to 5 mGy resulted in enhanced NOX4 expression by about 40% in
      both TP53 WT and Mut cells, in contrast to only a 1-2% increase following a 2 Gy
      only exposure. Utilizing mixed cultures of HCT116 TP53 WT and isogenic null Mut
      cells, as few as 10% TP53 Mut cells were sufficient to control the expression of
      the remaining 90% WT cells and resulted in an overall radio-sensitization
      response accompanied by the nuclear translocation of survivin characteristic of
      homogeneous TP53 Mut populations.

PMID- 29660404
TI  - Effect of humidity on photoinduced radicals in human hair.
AB  - EPR spectroscopy was used to monitor formation of free radicals in human hair
      upon UV irradiation. While the EPR spectra of brown hair were dominated by
      melanin signal, those of white hair were keratin-derived. The decay of UV induced
      keratin radicals was enhanced at increased ambient humidity. We argue that at
      higher humidity the swollen hair provides a more liquid-like environment, and
      higher molecular mobility in this environment leads to faster radical reactions.
      This interpretation is consistent with the increased UV-triggered protein damage
      in hair at high humidity as demonstrated by the protein loss, MALDI-TOF and FT-IR
      data.

PMID- 29660405
TI  - Microbiome-mediated bile acid modification: Role in intestinal drug absorption
      and metabolism.
AB  - Once regarded obscure and underappreciated, the gut microbiota (the microbial
      communities colonizing the gastrointestinal tract) is gaining recognition as an
      influencer of many aspects of human health. Also increasingly apparent is the
      breadth of interindividual variation in these co-evolved microbial-gut
      associations, presenting novel quests to explore implications for disease and
      therapeutic response. In this respect, the unearthing of the drug-metabolizing
      capacity of the microbiota has provided impetus for the integration of
      microbiological and pharmacological research. This review considers a potential
      mechanism, 'microbial bile acid metabolism', by which the intricate interplay
      between the host and gut bacteria may influence drug pharmacokinetics. Bile salts
      traditionally regarded as biological surfactants, synthesized by the host and
      biotransformed by gut bacteria, are now also recognized as signalling molecules
      that affect diverse physiological processes. Accumulating data indicate that bile
      salts are not equivalent with respect to their physicochemical properties,
      micellar solubilization capacities for poorly water-soluble drugs,
      crystallization inhibition tendencies nor potencies for bile acid receptor
      activation. Herein, the origin, physicochemical properties, physiological
      functions, plasticity and pharmaceutical significance of the human bile acid pool
      are discussed. Microbial dependant differences in the composition of the human
      bile acid pool, simulated intestinal media and commonly used preclinical species
      is highlighted to better understand in vivo performance predictiveness. While the
      precise impact of an altered gut microbiome, and consequently bile acid pool, in
      the biopharmaceutical setting remains largely elusive, the objective of this
      article is to aid knowledge acquisition through a detailed review of the
      literature.

PMID- 29660406
TI  - Is antimicrobial administration to food animals a direct threat to human health?
      A rapid systematic review.
AB  - BACKGROUND: Large quantities of antimicrobials are given to food animals,
      particularly in feed, potentially increasing antimicrobial resistance in humans.
      However, the magnitude of this effect is unclear. METHODS: We searched PubMed,
      Embase and Web of Science for studies on interventions that limited antimicrobial
      use in food animals, in any setting and context, to reduce antimicrobial
      resistance 1) in those food animals; and 2) in humans. We validated our strategy
      by testing whether it identified known relevant studies. Data from included
      studies were extracted into pre-designed and pilot-tested forms. RESULTS: We
      included 104 articles containing 93 studies. Heterogeneity (different animal
      species, environs, antimicrobial classes, interventions, administration routes,
      sampling, and methods), was considerable, precluding meta-analysis. The evidence
      was therefore synthesised narratively. A total of 89 studies (3 directly, 86
      indirectly) addressed whether limiting antimicrobial exposure in food animals led
      to decreased antimicrobial resistance in those animals. The evidence was adequate
      to conclude this, although the magnitude of the effect could not be quantified.
      Four studies (1 directly, 3 indirectly) examined whether withdrawal of
      antibiotics changed resistance of potential pathogens in retail food for human
      consumption, and in bacteria of humans themselves. The direct (observational)
      study of broiler hatchery in ovo antimicrobial injection found a credible effect
      in terms of size reduction and time sequences. INTERPRETATION: Limiting
      antimicrobial use in food animals reduces antimicrobial resistance in food
      animals, and probably reduces antimicrobial resistance in humans. The magnitude
      of the effect cannot be quantified.

PMID- 29660408
TI  - Expansion of the clinical spectrum of frontometaphyseal dysplasia 2 caused by the
      recurrent mutation p.Pro485Leu in MAP3K7.
AB  - Frontometaphyseal dysplasia 2 (FMD2) is a skeletal dysplasia with supraorbital
      hyperostosis combined with undermodeling of the bones, joint contractures and
      some extraskeletal features. It is caused by heterozygous mutations in MAP3K7,
      encoding the Mitogen-Activated Protein 3-Kinase 7. MAP3K7 is activated by TGF
      beta and plays an important role in osteogenesis. Less than 20 patients with FMD2
      and MAP3K7 mutations have been described thus far. The majority of the patients
      harbor a recurrent missense mutation, NM_003188.3: c.1454C > T [NP_003179.1:
      p.(Pro485Leu)], which leads to a more severe phenotype than mutations in other
      domains. Here we describe an additional patient with FMD2 caused by the recurrent
      c.1454C > T MAP3K7 mutation, identified as a de novo variant by whole-genome
      sequencing. The 17-year-old boy has the characteristic skeletal and facial
      features of FMD2. However, some novel features were also observed, including
      growth retardation and spina bifida occulta. In line with other patients
      harboring the same mutation he also showed keloid scars and had no intellectual
      disability. This report expands the clinical spectrum of FMD2 caused by the
      recurrent c.1454C > T [p.(Pro485Leu)] mutation in MAP3K7.

PMID- 29660407
TI  - Application of water-soluble polyvinyl alcohol-based film patches on laser
      microporated skin facilitates intradermal macromolecule and nanoparticle
      delivery.
AB  - The intradermal delivery of biologics has long been recognized as attractive
      approach for cutaneous immunotherapy, particularly vaccination. Although
      intradermal (i.d.) or subcutaneous (s.c.) injection provide reproducible dosing
      and good cost- and delivery efficiency, the major objective to avoid sharps and
      the need for enhanced storage stability have renewed the interest in alternative
      needle-free delivery strategies. This study presents a new concept for the
      delivery of macromolecules and nanoparticles to viable skin layers with a high
      density of professional antigen-presenting cells (APCs). Stable polyvinyl alcohol
      (PVA) polymer films as well as PVA blends with carboxymethyl cellulose (CMC) or
      cross-linked carbomer were prepared using an easily-scalable film casting
      technique. Fluorescein isothiocyanate (FITC) and rhodamine B-labeled dextrane 70
      kDa (RD70), used as small and macromolecular model substances, or polystyrene
      (PS)-nano- and microparticles with diameters of 0.5 um and 5 um were directly
      incorporated into the polymer formulations at varying concentrations. The
      assembly of the polymer films with an occlusive backing tape created a film patch
      that provided a fast drug release upon dissolution of the water-soluble film and
      facilitated an intradermal drug delivery on laser microporated skin. The
      minimally-invasive P.L.E.A.S.E.(r) laser poration system (Pantec Biosolutions,
      Ruggell, Liechtenstein) provided access to viable skin layers by thermally
      ablating the superficial tissue with a pulsed Er:YAG laser (lambda = 2.94 um). In
      our in vitro study using excised pig skin, laser microporation induced a 4- to 5
      fold increase of water transport (TEWL) through excised skin in a Franz diffusion
      cell compared to intact skin. The TEWL values detected were comparable to in vivo
      human skin. The increased water transport facilitated the dissolution of all
      topically applied dry PVA-based film formulations within 6 h. No dissolution of
      the films was seen on intact skin. The incubation of the film patches on laser
      microporated skin for 24 h led to a considerable intradermal delivery of RD70 or
      PS-nanoparticles, which was superior for pure PVA films compared to PVA-CMC or
      PVA-carbomer blend formulations. No intradermal delivery was observed on intact
      skin or when larger PS-microparticles with a diameter of 5 um were investigated.
      The presented concept provides a unique opportunity to exploit the improved
      storage stability of sensitive drug molecules in dry film formulations while
      providing protection and functionality.

PMID- 29660409
TI  - Chronic intestinal pseudo-obstruction syndrome and gastrointestinal malrotation
      in an infantwith schaaf-yang syndrome - Expanding the phenotypic spectrum.
AB  - We report a novel patient with the phenotypic characteristics of Schaaf-Yang
      syndrome. In addition, the patient has a severe chronic digestive malfunction,
      rendering him dependent on intermittent enteral supplementation. To our
      knowledge, this is the first report of Schaaf-Yang syndrome associated with
      severe chronic digestive malfunction manifesting with both a malrotation and
      signs of a chronic intestinal pseudo-obstruction.

PMID- 29660410
TI  - The spatial and developmental expression of mouse Vwa8 (von Willebrand domain
      containing protein 8).
AB  - The Drosophila gene c12.2 was isolated in a screen examining mRNA binding
      proteins. Drosophila c12.2 is the mouse Vwa8 homolog. Various genome-wide
      associated studies have linked human Vwa8 to both neurological and oncological
      pathologies, which include autism, bipolar disorder, comorbid migraine, and acute
      myeloid leukemia, however, the function and role of the VWA8 protein remain
      poorly understood. To further analyze the Vwa8 gene in mouse, gene structure,
      protein homology modeling, and gene expression patterns were examined throughout
      mouse development. Our analyses indicate that the mouse Vwa8 gene produces two
      transcripts; the full-length Vwa8a is highly expressed relative to the truncated
      Vwa8b transcript across all developmental time points and tissues analyzed.
      Protein homology modeling indicates that VWA8a belongs to a novel protein
      superfamily containing both the midasin and cytoplasmic dynein 1 heavy chain 1
      proteins. These data establish the development timeline and expression profile
      for both Vwa8a and Vwa8b, paving the way for future studies to determine the
      cellular role(s) of this highly conserved protein family.

PMID- 29660411
TI  - Decreased glycopeptide susceptibility in Staphylococcus pasteuri associated with
      a mutation in uncharacterised conserved membrane protein STP1_1701.

PMID- 29660412
TI  - Mycoplasma hominis shows strain-dependent increase in resistance to selected
      antibiotics after symbiosis with Trichomonas vaginalis.
AB  - OBJECTIVES: Mycoplasma hominis, a genetically heterogeneous, cell-wall-less
      bacterium, is able to live in symbiosis with the protozoan parasite Trichomonas
      vaginalis. Whilst the impact of this symbiosis on T. vaginalis has been
      investigated to a certain extent, less light has been shed on the influence on M.
      hominis. METHODS: An in vitro minimum inhibitory concentration (MIC) study of the
      antimicrobial susceptibility of three clinical M. hominis isolates (V475, AKH136
      and MhSS10) to clindamycin, moxifloxacin, ciprofloxacin and gentamicin was
      performed in dependence on symbiosis with T. vaginalis strain IR78. RESULTS:
      Passaging of M. hominis through T. vaginalis led to an increase in MICs to all
      drugs investigated in M. hominis V475 and M. hominis MhSS10 (apart from
      gentamicin). Shifts from intermediate to resistant (MhSS10 for ciprofloxacin) and
      from susceptible to intermediate-resistant (V475 for gentamicin; P=0.015) were
      observed. Moreover, initial susceptibility of V475 to moxifloxacin
      (MIC=1.35MUg/mL) was statistically significantly reduced (MIC=2.5MUg/mL)
      following T. vaginalis passage concomitantly with mutations in the quinolone
      resistance-determining regions (QRDRs) of gyrA (S153L) and parC (E195G and
      K144R). In contrast, the susceptibility of M. hominis isolate AKH136 to all drugs
      investigated increased after passaging. CONCLUSIONS: These findings suggest that
      symbiosis with T. vaginalis has an enhancing effect on selected antimicrobial
      resistances of distinct M. hominis isolates.

PMID- 29660413
TI  - Validation of French upper limb Erasmus modified Nottingham Sensory Assessment in
      stroke.
AB  - BACKGROUND: Somatosensory impairment of the upper limb (UL) occurs in
      approximately 50% of adults post-stroke, associated with loss of hand motor
      function, activity and participation. Measurement of UL sensory impairment is a
      component of rehabilitation contributing to the selection of sensorimotor
      techniques optimizing recovery and providing a prognostic estimate of UL
      function. To date, no standardized official French version of a measure of
      somatosensory impairment has been established. OBJECTIVE: To develop and validate
      a French version of the Erasmus modified Nottingham Sensory Assessment
      somatosensory (EmNSA-SS) and stereognosis (EmNSA-ST) component for evaluating the
      UL among adults with stroke. METHODS: This study is a single-center observational
      cross-sectional study. A French version of the EmNSA for UL was developed by
      forward-backward translation and cross-cultural adaptation. Fifty stroke patients
      were recruited to establish concurrent-criterion-related validity, internal
      consistency, intra- and inter-rater reproducibility with intracorrelation
      coefficients (ICCs) for reliability and the minimal detectable change with 95%
      confidence interval (MDC95) for agreement, as well as ceiling and floor effects.
      Criterion validity was assessed against the Fugl-Meyer Assessment-Sensory (FMA-S)
      for the UL. RESULTS: The median (range) EmNSA-SS score was 41.5 (1-44). The
      Spearman rank correlation coefficient between EmNSA-SS and FMA-S total scores was
      moderate (rho=0.74, P<0.001). The EmNSA-SS/ST internal consistency was adequate
      across subscales; with Cronbach alpha ranging from 0.82-0.96. For the EmNSA-SS
      total score, intra- and inter-rater reliability was excellent (ICC=0.92 in both
      cases), with MDC95 of 12.3 and 14.6, respectively. EmNSA-SS/ST total scores
      demonstrated no ceiling or floor effects. CONCLUSIONS: The French EmNSA is a
      valid and reproducible scale that can be used for comprehensive and accurate
      assessment of somatosensory modalities in adults post-stroke. Taking less than
      30min to administer, the instrument has clinical utility for use in patients with
      cognitive comorbidities and at various stages of recovery in multidisciplinary
      clinical practice and research settings.

PMID- 29660415
TI  - Towards a model-based cognitive neuroscience of stopping - a neuroimaging
      perspective.
AB  - Our understanding of the neural correlates of response inhibition has greatly
      advanced over the last decade. Nevertheless the specific function of regions
      within this stopping network remains controversial. The traditional neuroimaging
      approach cannot capture many processes affecting stopping performance. Despite
      the shortcomings of the traditional neuroimaging approach and a great progress in
      mathematical and computational models of stopping, model-based cognitive
      neuroscience approaches in human neuroimaging studies are largely lacking. To
      foster model-based approaches to ultimately gain a deeper understanding of the
      neural signature of stopping, we outline the most prominent models of response
      inhibition and recent advances in the field. We highlight how a model-based
      approach in clinical samples has improved our understanding of altered cognitive
      functions in these disorders. Moreover, we show how linking evidence-accumulation
      models and neuroimaging data improves the identification of neural pathways
      involved in the stopping process and helps to delineate these from neural
      networks of related but distinct functions. In conclusion, adopting a model-based
      approach is indispensable to identifying the actual neural processes underlying
      stopping.

PMID- 29660414
TI  - Nonlinear Inverted-U Shaped Relationship Between Aging and Epidermal Innervation
      in the Rat Plantar Hind Paw: A Laser Scanning Confocal Microscopy Study.
AB  - : The under-reporting of pain and atypical manifestations of painful syndromes
      within the elderly population have been well documented, however, the specific
      relationship between pain and aging remains ambiguous. Previous studies have
      reported degenerative changes in primary afferents with aging. In this study, we
      questioned whether there is any change in the density of primary afferent endings
      within the epidermis of aged animals. Rats were categorically assessed in 4 age
      groups, each representing a key developmental stage across their life span:
      juvenile (2 months), adult (7 months); aged (18 months), and senescent (24-26
      months). The plantar hind paw skin was removed, post-fixed, cut, and
      immunostained for protein gene product 9.5 and type IV collagen. Rats in the
      adult aged groups had significantly increased epidermal nerve densities and total
      lengths of immunoreactive nerve fibers, compared with juvenile as well as
      senescent rats. However, the paw withdrawal thresholds to punctate mechanical
      stimulation progressively increased with age, and did not exhibit a clear
      relationship with epidermal innervation. We conclude a nonlinear, inverted-U
      shaped relationship between rat plantar epidermal nerve density with aging, which
      does not correlate with mechanically-induced paw withdrawal behaviors.
      PERSPECTIVE: This article presents age-related decreased epidermal innervation in
      rat hind paw skin, which partly explains mechanisms underlying decreased pain
      sensitivity in aged subjects. The report may help clinicians to understand that
      any compromise of pain-sensing pathway can lead to under-reporting of pain,
      inadequate analgesia, and slower recovery from a painful condition.

PMID- 29660416
TI  - Cognitive effects of transcranial direct current stimulation treatment in
      patients with major depressive disorder: An individual patient data meta-analysis
      of randomised, sham-controlled trials.
AB  - Transcranial direct current stimulation (tDCS) has emerged as a promising new
      treatment for major depression. While recent randomised, sham-controlled studies
      found tDCS to have antidepressant effects, it remains to be determined whether a
      tDCS treatment course may also enhance cognitive function independent of mood
      effects in depressed patients. This systematic review and individual patient data
      (IPD) meta-analysis examined cognitive outcomes from randomised, sham-controlled
      trials of tDCS treatment for major depression. Seven randomised, sham-controlled
      trials (n = 478 participants, 260 in active and 218 in sham) of tDCS for major
      depression were included. Results showed no cognitive enhancement after active
      tDCS compared to sham for the 12 cognitive outcomes investigated. Active relative
      to sham tDCS treatment was associated with reduced performance gains on a measure
      of processing speed (beta = -0.33, 95% CI -0.58; -0.08, p = 0.011). Active tDCS
      treatment for depression did not show cognitive benefits independent of mood
      effects. Rather, tDCS treatment relative to sham stimulation for major depression
      may instead be associated with a reduced practice effect for processing speed.

PMID- 29660418
TI  - Evolution of cooperation in a hierarchical society with corruption control.
AB  - Punishment is widely recognized as a potential promoter in sustaining or even
      enhancing public cooperation, but it meanwhile induces the problem of second
      order free-riders. Particularly, recent evidence shows that costly punishment can
      be maintained if punishers may engage in corruption. However, how to reduce or
      eliminate incidents of corruption has been the enduring conundrum in human
      society. As power asymmetries are associated with hierarchies, we investigate how
      costly punishment affects the evolution of cooperation in the cases without and
      with corruption control. In the absence of corruption control, altruistic
      punishers are incapable of punishing corrupt punishers. Corrupt punishment
      maintains civilian cooperation but undermines the evolution of altruistic
      punishment. Otherwise, altruistic punishers can enforce symmetrical or
      asymmetrical punishment on both corrupt punishers and civilian defectors. In this
      case, both civilian cooperation and altruistic punishment can be promoted. And as
      an instrument of corruption control, the policy of asymmetrical punishment is
      more effective in fostering public cooperation and improving social welfare than
      symmetrical punishment. Moreover, no matter whether corruption control is
      considered or not, spiteful corruption that non-cooperative punishers penalize
      defectors is a more effective form for enhancing cooperation compared with
      bribery. Our work may thus offer an insight into the effects of corruption on
      public cooperation and the policy of anti-corruption.

PMID- 29660419
TI  - Effective leg stiffness of animal running and the co-optimization of energetic
      cost and stability.
AB  - The relative leg stiffness of most running animals falls in a small range between
      7 and 27. Here we present a theoretical study of an established running model, an
      actuated Spring Loaded Inverted Pendulum model, to determine if the energetic
      cost and stability of running might be co-optimized over this range of leg
      stiffness values. The energetic cost of the model is quantified as the energy
      spent to move a unit mass a unit distance. The stability of the model is based on
      the system response to perturbations with respect to periodic locomotion
      solutions, and uses the linearized dynamics of Poincare return maps and the
      resulting maximum eigenvalue and singular value decomposition in order to analyze
      asymptotic stability and the overall system response to perturbations,
      respectively. We find that there exists a tradeoff between stability and
      energetic cost in the model with respect to variation in forcing (actuation)
      level: For a given leg stiffness, the energetic cost tends to be more optimal
      with smaller forcing, and the opposite for stability. We find that intermediate
      levels of forcing can achieve near asymptotic stability or complete asymptotic
      stability while remaining small enough to yield a relatively low energetic cost
      consistent with human-like values. We demonstrate that this outcome can be
      achieved in the model with a simple optimization function that balances stability
      and energetic cost. We then investigate the stability and energetic cost when
      both leg stiffness and forcing are varied. Overall, the analysis shows that leg
      stiffness values in or near the biological range offers a good chance of
      simultaneously achieving both reasonable energetic cost and stability in the
      model. The results of this study suggest that stability and energetic cost may be
      interacting factors that have a combined influence on the effective leg stiffness
      and actuation (forcing) used by running animals.

PMID- 29660420
TI  - Tracking tumor kinetics in patients with germline CYLD mutations.

PMID- 29660421
TI  - Certolizumab pegol for the treatment of chronic plaque psoriasis: Results through
      48 weeks from 2 phase 3, multicenter, randomized, double-blinded, placebo
      controlled studies (CIMPASI-1 and CIMPASI-2).
AB  - BACKGROUND: Certolizumab pegol, the only Fc-free, PEGylated anti-tumor necrosis
      factor biologic, demonstrated clinically meaningful improvements suggestive of a
      positive risk-benefit balance in phase 2 studies in adults with moderate-to
      severe chronic plaque psoriasis. OBJECTIVE: Assess certolizumab efficacy and
      safety versus placebo in phase 3 studies. METHODS: Patients with moderate-to
      severe chronic plaque psoriasis were randomized 2:2:1 to certolizumab 400 mg,
      certolizumab 200 mg, or placebo every 2 weeks. At week 16, certolizumab-treated
      patients achieving a 50% reduction in Psoriasis Area and Severity Index continued
      treatment through week 48. Coprimary endpoints were week 16 responder rates,
      defined as a 75% reduction in Psoriasis Area and Severity Index and Physician's
      Global Assessment 0/1 (clear/almost clear) and >=2-point improvement. Safety was
      assessed by treatment-emergent adverse events. RESULTS: Week-16 endpoints were
      significantly greater for both doses of certolizumab versus placebo, and the
      responses were maintained through week 48. For most measures, improvement was
      numerically greater for certolizumab 400 mg. No unexpected safety signals were
      identified. LIMITATION: There was no active comparator. CONCLUSION: Treatment
      with either certolizumab 400 mg or 200 mg every 2 weeks was associated with
      significant and clinically meaningful improvements in moderate-to-severe
      psoriasis. The 400-mg dose could provide additional clinical benefit. The safety
      profile was consistent with the therapeutic class.

PMID- 29660417
TI  - RDoC-based categorization of amygdala functions and its implications in autism.
AB  - Confusion endures as to the exact role of the amygdala in relation to autism. To
      help resolve this we turned to the NIMH's Research Domain Criteria (RDoC) which
      provides a classification schema that identifies different categories of
      behaviors that can turn pathologic in mental health disorders, e.g. autism. While
      RDoC incorporates all the known neurobiological substrates for each domain, this
      review will focus primarily on the amygdala. We first consider the amygdala from
      an anatomical, historical, and developmental perspective. Next, we examine the
      different domains and constructs of RDoC that the amygdala is involved in:
      Negative Valence Systems, Positive Valence Systems, Cognitive Systems, Social
      Processes, and Arousal and Regulatory Systems. Then the evidence for a
      dysfunctional amygdala in autism is presented with a focus on alterations in
      development, prenatal valproic acid exposure as a model for ASD, and changes in
      the oxytocin system therein. Finally, a synthesis of RDoC, the amygdala, and
      autism is offered, emphasizing the task of disambiguation and suggestions for
      future research.

PMID- 29660424
TI  - Dermoscopic features of onychotillomania: A study of 36 cases.
AB  - BACKGROUND: Onychotillomania is a nail-picking disorder characterized by nail
      dystrophy and abnormal morphology of the nail plate, nail bed, and periungual
      skin. OBJECTIVE: The purpose of this study was to describe the dermoscopic
      features of onychotillomania. METHODS: A retrospective study of the dermoscopy
      images of 36 patients affected by onychotillomania. The images were reviewed
      independently by both authors and a list of dermatoscopic findings was
      established. RESULTS: Scales were observed in 34 cases (94.4%). Absence of the
      nail plate was seen in 30 cases (83.3%). Wavy lines were observed in 25 cases
      (69.4%). Hemorrhages were observed in 23 cases (63.9%). Crusts were seen in 22
      cases (61.1%). Nail bed pigmentation was observed in 17 cases (47.2%). Speckled
      dots were observed in 14 cases (38.9%). Nail plate melanonychia was observed in 4
      cases (11.1%). LIMITATIONS: Limitations included small sample size and
      retrospective study. CONCLUSION: Absence of the nail plate with multiple
      obliquely oriented nail bed hemorrhages, nail bed gray pigmentation, and presence
      of wavy lines are characteristic findings of onychotillomania and not seen in
      other nail diseases.

PMID- 29660423
TI  - CME Part 2: Hair disorders in cancer survivors Persistent chemotherapy-induced
      alopecia, persistent radiotherapy-induced alopecia, and hair growth disorders
      related to endocrine therapy or cancer surgery.
AB  - With increasing survival rates across all cancers, survivors represent a growing
      population that is frequently affected by persistent or permanent hair growth
      disorders as a result of systemic therapies, radiotherapy, surgical procedures,
      and therapeutic transplants. These hair disorders include persistent chemotherapy
      induced alopecia, persistent radiotherapy-induced alopecia, endocrine therapy
      induced alopecia and hirsutism, post-surgery alopecia and localized
      hypertrichosis, alopecia attributed to therapeutic transplants, and to novel
      anticancer therapies. The information contained in this continuing medical
      education article should facilitate a better understanding on hair disorders in
      cancer survivors, so that adequate support and therapies may be provided to
      cancer survivors.

PMID- 29660422
TI  - CME Part 1: Hair disorders in cancer patients.
AB  - Cytotoxic chemotherapies, molecularly targeted therapies, immunotherapies,
      radiotherapy, stem cell transplants, and endocrine therapies may lead to hair
      disorders (including alopecia, hirsutism, hypertrichosis, pigmentary and textural
      hair changes). The mechanisms underlying these changes are varied and remain
      incompletely understood, hampering the development of preventive or therapeutic
      guidelines. The psychosocial impact of chemotherapy -induced alopecia has been
      well-documented mainly in the oncology literature, however the effect of other
      alterations such as radiation-induced alopecia, hirsutism, changes in hair color
      or texture on quality of life have not been described. This article reviews
      clinically significant therapy-related hair disorders in cancer patients,
      underlying pathophysiological mechanisms, severity grading scales, patient
      reported quality of life instruments, management strategies, and future
      translational research opportunities.

PMID- 29660425
TI  - Certolizumab pegol for the treatment of chronic plaque psoriasis: Results through
      48 weeks of a phase 3, multicenter, randomized, double-blind, etanercept- and
      placebo-controlled study (CIMPACT).
AB  - BACKGROUND: Phase 2 psoriasis studies with the Fc-free, PEGylated, anti-tumor
      necrosis factor biologic certolizumab pegol demonstrated meaningful clinical
      activity. OBJECTIVE: Assess safety and efficacy of certolizumab in adults with
      moderate-to-severe chronic plaque psoriasis. METHODS: Patients were randomized
      3:3:1:3 to certolizumab 400 mg, certolizumab 200 mg, or placebo every 2 weeks for
      16 weeks or etanercept 50 mg twice weekly for 12 weeks. Certolizumab-treated
      patients achieving a >=75% reduction in Psoriasis Area and Severity Index (PASI)
      at week 16 from baseline PASI were rerandomized to certolizumab or placebo for 32
      weeks. The primary endpoint was responder rate (>=75% reduction in PASI from
      baseline PASI) versus placebo (primary analysis) and etanercept (secondary
      analysis) at week 12; secondary endpoints included responder rates on various
      measures versus placebo at weeks 12, 16, and 48. Safety was assessed by treatment
      emergent adverse events. RESULTS: All endpoints were significantly greater for
      certolizumab versus placebo with the greatest response seen with 400 mg.
      Certolizumab 400 mg was superior to and 200 mg was noninferior to etanercept.
      Adverse events were consistent with the anti-tumor necrosis factor class of
      drugs. LIMITATIONS: Etanercept was administered by unblinded study staff or self
      administered, but efficacy assessments were performed by a blinded assessor.
      CONCLUSION: Both certolizumab regimens improved psoriasis symptoms, with a
      greater response seen with the higher dose. No new safety signals were observed.

PMID- 29660426
TI  - Coffee and tea drinking in relation to risk of hip fracture in the Singapore
      Chinese Health Study.
AB  - Meta-analyses of studies conducted among Western populations suggest that coffee
      consumption does not affect osteoporotic fracture risk. However, experimental
      studies have shown that the effect of caffeine on bone health may depend on
      dosage. We examined the associations between consumption of coffee, tea and
      caffeine and risk of hip fracture in an Asian cohort. In a population-based
      prospective cohort of 63,257 Chinese men and women aged 45-74 years in Singapore,
      a validated semi-quantitative food frequency questionnaire was used to assess
      habitual consumption of coffee and tea at baseline. Cox proportional hazards
      regression models were used to estimate hazard ratio (HR) and 95% confidence
      interval (CI) for risk of hip fracture with adjustment for potential confounders.
      During a mean follow-up of 16.7 years, 2502 incident hip fracture cases were
      identified. Compared to coffee drinkers <1 cup/week, those who drank >=4 cups/day
      had a statistically significant higher risk to develop hip fractures, the HR (95%
      CI) was 1.32 (1.07, 1.63) in the whole cohort analysis, 1.46 (1.01, 2.10) for men
      and 1.33 (1.02, 1.72) for women. Among postmenopausal women, compared to those
      who drank coffee <1 cup/week, drinking 2-3 cups/day was associated with the
      lowest risk [HR: 0.88 (0.76, 1.01)] and drinking >=4 cups/day was associated with
      the highest risk [HR: 1.31 (1.00, 1.71)]. Similar associations with caffeine
      intake were found among postmenopausal women. Restricted spline analyses
      suggested a non-linear association between coffee/caffeine consumption and hip
      fracture risk in postmenopausal women (p for non-linearity <= 0.05). No
      association was found with tea consumption in either sex. These data suggest that
      drinking coffee >=4 cups/day is associated with a higher hip fracture risk, while
      a moderate intake may alleviate risk in postmenopausal women. Future studies
      should corroborate these results to determine levels of optimal coffee
      consumption in relation to bone health.

PMID- 29660427
TI  - Epiphyseal growth plate architecture is unaffected by early postnatal activation
      of the expression of R992C collagen II mutant.
AB  - Spondyloepiphyseal dysplasia (SED) exemplifies a group of heritable diseases
      caused by mutations in collagenous proteins of the skeletal system. Its main
      feature is altered skeletal growth. Pathomechanisms of SED include: changes in
      the stability of collagen II molecules, inability to form proper collagen
      fibrils, excessive intracellular retention of mutant molecules, and endoplasmic
      reticulum stress. The complexity of this pathomechanism presents a challenge for
      designing therapies for SED. Our earlier research tested whether such therapies
      only succeed when applied during a limited window of development. Here, employing
      an inducible mouse model of SED caused by the R992C mutation in collagen II, we
      corroborate our earlier observations that a therapy must be applied at the
      prenatal or early postnatal stages of skeletal growth in order to be successful.
      Moreover, we demonstrate that blocking the expression of the R992C collagen II
      mutant at the early prenatal stages leads to long-term positive effects.
      Although, we could not precisely mark the start of the expression of the mutant,
      these effects are not significantly changed by switching on the mutant production
      at the early postnatal stages. By demonstrating the need for early therapeutic
      interventions, our study provides, for the first time, empirically-based
      directions for designing effective therapies for SED and, quite likely, for other
      skeletal dysplasias caused by mutations in key macromolecules of the skeletal
      system.

PMID- 29660428
TI  - The Kinetics of Antidrug Antibodies, Drug Levels, and Clinical Outcomes in
      Infliximab-Exposed Patients with Immune-Mediated Disorders.
AB  - BACKGROUND: Hypersensitivity reactions (HRs) and loss of response (LOR) to
      infliximab (IFX) are related to drug immunogenicity characterized by antidrug
      antibodies (ADAs). OBJECTIVE: To analyze the timing of ADA appearance and its
      relationship with drug levels and clinical outcomes in IFX-treated patients with
      different diseases. METHODS: Samples were longitudinally collected before each
      infusion from 91 IFX-treated patients and were assayed for ADA and drug levels by
      enzyme-linked immunosorbent assay and for IgE by ImmunoCAP system. Clinical data
      regarding efficacy and safety of therapy were also monitored. RESULTS: The ADA
      onset occured quite early, irrespective of the type of disease, during the first
      year and more frequently and earlier during the second cycle of therapy. Patients
      with HR were more frequently ADA-positive and with higher ADA titers compared
      with other patient groups. ADA onset tends to precede HRs and LOR; all HRs that
      occur after a period of drug interruption are preceded by ADA development. Before
      ADA detection, a progressive decline in IFX levels until a complete disappearance
      was observed. The ADA titer was maintained for years both in patients with
      ongoing therapy and in those who interrupted it. IgE ADAs are more frequently
      developed in patients with higher ADA levels and earlier ADA onset, but their
      rate of negativization is faster. CONCLUSION: The present data suggest that most
      IFX-exposed patients develop ADAs within the first year of treatment irrespective
      of disease type. The clinical outcome to the treatment is preceded by ADA
      development, which in turn is associated with the reduction in drug serum levels.
      Both ADA evaluation and therapeutic drug monitoring may have a relevant impact on
      clinical practice, giving new insights to predict LOR and HRs.

PMID- 29660429
TI  - Summary and simulation of reported adverse events from epinephrine autoinjectors
      and a review of the literature.

PMID- 29660430
TI  - The protective effect of Hif3a RNA interference and HIF-prolyl hydroxylase
      inhibition on cardiomyocytes under anoxia-reoxygenation.
AB  - The aim of this study was to investigate the molecular mechanisms underlying the
      protective effects of hypoxia-inducible factor (HIF) signaling pathway activation
      in cardiomyocytes under anoxia-reoxygenation (A/R) injury. In this study, rat
      neonatal cardiomyocytes were pretreated with anti-Hif3A/Hif-3alpha siRNA or HIF
      prolyl hydroxylase inhibitor prior to A/R injury. Our results showed that both
      HIF3A silencing and HIF-prolyl hydroxylase inhibition effectively increased the
      cell viability during A/R, led to changes in mRNA expression of HIF1-target
      genes, and reduced the loss of mitochondrial membrane potential (Deltapsim).
      Furthermore, application of anti-Hif3a siRNA led to an increase in mRNA
      expression of Epo, Igf1, Slc2a1/Glut-1, and Slc2a4/Glut-4. Similar results were
      observed with HIF-prolyl hydroxylase inhibition, which additionally upregulated
      the mRNA expression of Epor, Tert, and Pdk1. Hif3a RNA-interference and
      application of HIF-prolyl hydroxylase inhibitor during A/R modelling led to an
      increase of Deltapsim on 11.5 and 11.9 mV respectively, compared to the control
      groups. Thus, Hif3a RNA interference and HIF-prolyl hydroxylase inhibition
      protect cardiomyocytes against A/R injury via the HIF signaling pathway.

PMID- 29660431
TI  - Electroacupuncture ameliorates poloxamer 407-induced hyperlipidemia through
      suppressing hepatic SREBP-2 expression in rats.
AB  - AIMS: Acupuncture, particularly electroacupuncture (EA) has been shown to have
      the lipid-lowering effects, but not completely investigated. The present study
      was aimed to examine whether EA could attenuate poloxamer-407 (P-407)-induced
      hyperlipidemia in the rats and to investigate its potential mechanisms. MAIN
      METHODS: Rats received P-407 (0.4 g/kg, i.p.) to induce hyperlipidemia. EA was
      performed at ST36 and ST40 acupoints a total of three times with 12 h-interval
      starting 1 h before the P-407 injection at 0.6 mA intensity and 2 Hz frequency
      for 10 min. KEY FINDINGS: In P-407-induced hyperlipidemic rats, EA stimulation at
      ST36 and ST40 acupoints significantly lowered the serum levels of triglycerides,
      total cholesterol, LDL-cholesterol and atherogenic index, while markedly
      increasing the serum HDL-cholesterol levels. Meanwhile, hyperlipidemic rats had
      significantly higher expression of sterol regulatory element-binding protein
      (SREBP)-2, without any difference in SREBP-1 expression in the liver, as compared
      with normal ones. EA significantly attenuated the expression of SREBP-2 with a
      subsequent decrease in 3-hydroxy-3-methylglutaryl coenzyme A reductase and an
      increase in low-density lipoprotein receptor at both mRNA and protein levels in
      the liver of hyperlipidemic rats. These changes did not occur after electrical
      stimulation at a non-acupoint. SIGNIFICANCE: Taken together, our findings
      indicate that EA stimulation to P-407-induced hyperlipidemic rats improves the
      lipid abnormalities, which may be associated with regulation of the expression of
      key enzymes of cholesterol synthesis in the liver through modulation of SREBP-2.

PMID- 29660432
TI  - Evaluation of hematological and biochemical parameters of pesticide retailers
      following occupational exposure to a mixture of pesticides.
AB  - AIMS: This study was undertaken to ascertain whether light occupational exposure
      to pesticides by retailers might be associated with any liver, kidney, nervous
      system dysfunction or hematological abnormalities. MAIN METHODS: In this cross
      sectional study, 70 male pesticide retailers (cases) and 64 male subjects,
      randomly selected from the constructions workers of city council contractors, as
      the referent group, were investigated. Urine and blood samples were taken from
      all subjects for urine analysis, hematological and biochemical parameters. Data
      analysis was conducted through SPSS v.19 using t-test and chi-square test. KEY
      FINDINGS: The results of urine analysis showed that the frequency of abnormal
      urine tests was significantly higher in cases than in referent individuals.
      Similarly, the results of CBC showed that the mean values of monocyte,
      hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin and
      platelet distribution width were significantly lower, and mean corpuscular
      hemoglobin concentration and red blood cell distribution width were significantly
      higher in retailers. No significant differences were found for other parameters.
      SIGNIFICANCE: These findings indicate that an association exists between exposure
      to pesticides by retailers and early subtle and sub-clinical changes in the urine
      tests and hematological parameters. Engineering measures are recommended to
      eliminate exposure to pesticides and to prevent its associated outcomes.

PMID- 29660433
TI  - Slit2-Robo2 signaling modulates the fibrogenic activity and migration of hepatic
      stellate cells.
AB  - BACKGROUND & AIM: Slit/Robo signaling was originally identified as a repulsive
      guidance cue in regulating axon branching and neuronal migration. Hepatic
      stellate cells (HSCs) are the key fibrogenic cells in the liver, which are
      migratory when activated, and express neural crest markers. The aim of the
      present study was to investigate the functional significance of Slit/Robo
      signaling in liver fibrogenesis and in HSCs. KEY FINDINGS: By transcriptomic
      analysis it was found that axon guidance signaling pathways were significantly
      upregulated in both diethylnitrosamine (DEN) and thioacetamide (TAA)-induced
      experimental liver fibrosis. The up-regulation of the ligand Slit2 and membrane
      receptor Robo2 genes within this pathway was further validated in TAA-induced
      fibrotic livers. By immunofluorescence staining, Robo2 was localized in fibrotic
      septa of fibrotic liver and on the surface of HSCs. By Western blot analysis,
      recombinant Slit2 (rSlit2) was found to promote fibrogenic protein expression in
      JS1 cells, an immortalized mouse HSC line, while activating PI3K/Akt signaling
      pathway. This effect was abrogated by LY294002, a PI3K/Akt pathway inhibitor. In
      addition, rSlit2 stimulation markedly inhibited JS1 cells migration in transwell
      migration assays, which was abrogated by small interfering RNA (siRNA) knockdown
      of Robo2 in the cells. SIGNIFICANCE: The present study provides evidence that
      Slit2/Robo2 signaling mediates the pathogenesis of hepatic fibrogenesis and
      regulates HSCs biology, thus providing potential markers for HSCs, and
      therapeutic and diagnostic target toward liver fibrosis.

PMID- 29660434
TI  - The beclomethasone anti-inflammatory effect occurs in cell/mediator-dependent
      manner and is additively enhanced by formoterol: NFkB, p38, PKA analysis.
AB  - AIMS: Beclomethasone/formoterol (BDP/FOR) has been reported to be more effective
      than its separate components in airway disease control and in airway inflammation
      improvement. However, BDP/FOR effects on cytokine-induced inflammation in
      structural cells have not been described and whether these effects occur in a
      cell- and mediator-dependent manner has not been fully elucidated. We sought to
      evaluate BDP and/or FOR effects on endothelial ICAM-1, E-selectin, IL-8 and on
      bronchial epithelial ICAM-1 and IL-8. Specific intracellular signaling pathways
      were also investigated. MATERIALS AND METHODS: Surface adhesion molecule
      expression and IL-8 release induced by TNF-alpha were measured by ELISA.
      Intracellular signaling pathways were investigated by a) EMSA and Western blot
      analysis to evaluate NF-kappaB DNA-binding and MAPK-p38 phosphorylation; b)
      PDTC/SB203580 as NF-kappaB/p38 inhibitors; c) forskolin/H-89 as PKA
      activator/inhibitor. KEY FINDINGS: BDP/FOR additively reduced endothelial E
      selectin and IL-8 as well as bronchial epithelial ICAM-1 and IL-8. BDP/FOR and
      SB203580 showed the highest inhibitory effect on epithelial IL-8, whereas
      endothelial ICAM-1 was never affected by BDP/FOR and PDTC. TNF-alpha-induced NF
      kappaB DNA-binding and MAPK-p38 phosphorylation were not influenced by BDP/FOR.
      Forskolin mimicked FOR effects; H-89 partially reversed the BDP/FOR inhibition in
      a mediator-dependent manner. SIGNIFICANCE: The BDP/FOR inhibition degree was
      related to the inflammatory mediator- and cell-type considered. FOR additively
      enhanced BDP effects by partially involving both dependent- and independent-PKA
      mechanisms. Our results might contribute to highlight the strong relationship
      between specific molecular pathways and different sensitivity to the
      corticosteroid/beta2-agonist effects and to clarify the molecular mechanisms
      underlying the BDP/FOR anti-inflammatory activity in vivo.

PMID- 29660435
TI  - Yangonin protects against cholestasis and hepatotoxity via activation of
      farnesoid X receptor in vivo and in vitro.
AB  - Cholestasis is a clinical syndrome with systemic and intrahepatic accumulation of
      excessive toxic bile acids that ultimately cause hepatobiliary injury. Recently
      obeticholic acid (OCA) which is a farnesoid X receptor (FXR) agonist was approved
      by FDA to treat cholestatic liver diseases, which provided us a newly therapeutic
      strategy against cholestasis. The purpose of the current study is to screen novel
      FXR agonists and verify the anti-cholestasis effect of yangonin in vivo and in
      vitro. The computational strategy of two-dimensional virtual screening was used
      to search for new FXR agonists, and dual-luciferase reporter gene assay was used
      to further demonstrate FXR activation by yangonin. Then, the hepatoprotective
      effect of yangonin via FXR activation against cholestasis and hepatotoxity was
      evaluated in mice and was investigated using FXR silence in cells. Yangonin was
      found to activate FXR to exert hepatoprotective effect against cholestatic liver
      injury. Dynamic change analysis of bile acids and gene analysis revealed that
      yangonin promoted bile acid efflux into bile and reduced hepatic uptake via the
      regulation of FXR-target genes Bsep, Mrp2 and Ntcp expression. Furthermore,
      yangonin modulated enzymes involved in bile acid synthesis and metabolism
      including Cyp7a1 Cyp8b1 and Sult2a1. In addition, yangonin promoted liver repair
      and suppressed liver inflammation. However, the changes in these genes and
      protein, as well as ameliorative liver histology induced by yangonin were
      abrogated by FXR antagonist guggulsterone in vivo and FXR siRNA in vitro.
      Yangonin produces protective effect against cholestasis via FXR activation.
      Yangonin may be an effective approach for the prevention and treatment for
      cholestatic liver diseases.

PMID- 29660436
TI  - In vitro study of doxorubicin-induced oxidative stress in spermatogonia and
      immature Sertoli cells.
AB  - Pediatric chemotherapy treatments can impair long-term male fertility.
      Unfortunately, no fertility preservation solution is available for pre-pubertal
      boys. Studies suggest that doxorubicin, used against pediatric cancers, induces
      oxidative stress in the testis. However, the targeted testicular cell types
      remain unknown. The goal of this study was to determine whether doxorubicin can
      induce oxidative stress in rat spermatogonia (GC-6Spg) and immature Sertoli (Ser
      W3) cell lines, and to assess their protection by antioxidants. Using the MTT
      assay, we have shown that doxorubicin induces a time- and dose-dependent
      cytotoxicity in these two cell lines, Ser-W3 being more sensitive than GC-6Spg.
      After 3 h of treatment, reactive oxygen species and nuclear 8-oxo-deoxyguanosine
      increase in Ser-W3, but not in GC-6Spg. Moreover, after 6 h of treatment,
      intracellular reduced glutathione levels decrease significantly in Ser-W3 cells.
      These results show that doxorubicin induces oxidative stress in the Ser-W3 cell
      line. However, a depletion in glutathione does not affect their survival, and
      supplementation only offers a weak protection after exposure to doxorubicin,
      suggesting that the glutathione system is not essential for Ser-W3 cell line's
      defense against doxorubicin. On the other hand, among four antioxidants selected
      from the literature, none reduces the cytotoxicity of doxorubicin in Ser-W3
      cells. Together, our data suggest that oxidative stress may not be a major
      pathway for doxorubicin's cytotoxicity in GC-6Spg and Ser-W3 lines. This study
      provides new insights in the mechanisms by which chemotherapies affect the pre
      pubertal testis, with the long-term goal to help improve the quality of life of
      pediatric cancer survivors.

PMID- 29660437
TI  - Deoxycholylglycine, a conjugated secondary bile acid, reduces vascular tone by
      attenuating Ca2+ sensitivity via rho kinase pathway.
AB  - Patients with cirrhosis have reduced systemic vascular resistance and elevated
      circulating bile acids (BAs). Previously, we showed that secondary conjugated BAs
      impair vascular tone by reducing vascular smooth muscle cell (VSMC) Ca2+ influx.
      In this study, we investigated the effect of deoxycholylglycine (DCG), on Ca2+
      sensitivity in reducing vascular tone. First, we evaluated the effects of DCG on
      U46619- and phorbol-myristate-acetate (PMA)-induced vasoconstriction. DCG reduced
      U46619-induced vascular tone but failed to reduce PMA-induced vasoconstriction.
      Then, by utilizing varied combinations of diltiazem (voltage-dependent Ca2+
      channel [VDCC] inhibitor), Y27632 (RhoA kinase [ROCK] inhibitor) and
      chelerythrine (PKC inhibitor) for the effect of DCG on U46619-induced
      vasoconstriction, we ascertained that DCG inhibits VDCC and ROCK pathway with no
      effect on PKC. We further assessed the effect of DCG on ROCK pathway. In beta
      escin-permeabilized arteries, DCG reduced high-dose Ca2+- and GTPgammaS (a ROCK
      activator)-induced vasoconstriction. In rat vascular smooth muscle cells (VSMCs),
      DCG reduced U46619-induced phosphorylation of myosin light chain subunit (MLC20)
      and myosin phosphatase target subunit-1 (MYPT1). In permeabilized VSMCs, DCG
      reduced Ca2+- and GTPgammaS-mediated MLC20 and MYPT1 phosphorylation, and
      further, reduced GTPgammaS-mediated membrane translocation of RhoA. In VSMCs,
      long-term treatment with DCG had no effect on ROCK2 and RhoA expression. In
      conclusion, DCG attenuates vascular Ca2+ sensitivity and tone via inhibiting ROCK
      pathway. These results enhance our understanding of BAs-mediated regulation of
      vascular tone and provide a platform to develop new treatment strategies to
      reduce arterial dysfunction in cirrhosis.

PMID- 29660438
TI  - Prenatal nicotine exposure intergenerationally programs imperfect articular
      cartilage via histone deacetylation through maternal lineage.
AB  - Accumulating evidence has shown that the impact of prenatal environmental factors
      on the organs of the offspring could last until the adulthood. Here, we aimed to
      investigate these effects and the potential mechanism of prenatal nicotine
      exposure (PNE) on the female adult cartilage of the first generation (PNE-F1) and
      the second generation (PNE-F2). Pregnant Wistar rats were injected with 2.0
      mg/kg.d nicotine from gestational day (GD) 9 to 20. Then their F1 generation at
      GD20 and postnatal week (PW) 12, and F2 generation at PW12 were harvested. The
      expression of extracellular matrix (ECM) and transforming growth factor beta
      (TGFbeta) signaling genes were analyzed by real-time quantitative PCR, and the
      histone acetylation was examined by chromatin immunoprecipitation assay. The
      results showed that PNE reduced the ECM and TGFbeta signaling gene expressions in
      both PNE-F1 and PNE-F2 female adult articular cartilage. In the F1 generation,
      PNE inhibited the acetylation at H3K9 of TGFbeta, TGFbeta receptor 1 (TGFbetaR1),
      SRY-type high mobility group box 9 (SOX9), a1 chain of type II collagen (COL2A1)
      and aggrecan (ACAN) gene promoters at both GD20 and PW12. In PNE-F2 at PW12, the
      obvious deacetylation at H3K9 of the TGFbetaR1 and COL2A1 promoters still
      existed. Moreover, in rat fetal chondrocytes, corticosterone rather than nicotine
      directly induced the hypoacetylation of H3K9 of TGFbetaR1 and COL2A1 genes, which
      might be the main cause of imperfect cartilage for PNE-F2. This study may be
      helpful to elucidate the developmental variability of articular cartilage quality
      and useful for the early prevention of articular damage.

PMID- 29660439
TI  - Activation of 5-HT1B receptors in the Lateral Habenula attenuates the anxiogenic
      effects of cocaine.
AB  - Recent work has implicated the Lateral Habenula (LHb) in the production of
      anxiogenic and aversive states. It is innervated by all the major monoamine
      neurotransmitter systems and has projections that have been shown to modulate the
      activity of both dopaminergic and serotonergic brain regions. Cocaine is a
      stimulant drug of abuse that potentiates neurotransmission in these monoamine
      systems and recent research suggests that the drug's behavioral effects may be
      related in part to its actions within the LHb. The present research was therefore
      devised to test the hypothesis that alterations in serotonin (5-HT) function
      within the LHb can affect the behavioral response to cocaine. Male rats were
      fitted with intracranial guide cannula and trained to traverse a straight
      alleyway once a day for a 1 mg/kg i.v. injection of cocaine. Intra-LHb
      pretreatment with the 5-HT1B agonist CP 94,253 (0, 0.1, or 0.25 MUg/side)
      attenuated the development of approach/avoidance "retreat" behaviors known to be
      a consequence of cocaine's dual rewarding (approach) and anxiogenic (avoidance)
      properties. This effect was reversed by co-administration of a selective 5-HT1B
      antagonist, NAS-181 (0.1 MUg/side), demonstrating drug specificity at the 5-HT1B
      receptor. These data suggest that 5-HT1B signaling within the LHb contributes to
      the anxiogenic effects of cocaine.

PMID- 29660440
TI  - The long-term effect of maternal dietary protein restriction on 5-HT1A receptor
      function and behavioral responses to stress in adulthood.
AB  - Maternal nutrition impacts fetal development, and may play a role in determining
      resilience to stress and vulnerability to stress-precipitated psychiatric
      disorders, such as anxiety and depression. In this study, we examined the effect
      of a reduction in maternal dietary protein during pregnancy on the brain
      neurochemistry and behavior of offspring. We focused specifically on the
      serotonin system, the 5-HT1A receptor and the responsivity of offspring as adults
      to stress. Dams were fed either a low protein diet (10% protein by weight) or
      isocaloric control diet (20% protein by weight). The low protein diet did not
      alter maternal food intake and body weight, or litter size and the average birth
      weight of male or female littermates. 5-HT1A receptor function, as measured by
      quantitative autoradiography of 8-OH-DPAT (1 MUM)-stimulated [35S]GTPgammaS
      binding, was markedly reduced in hippocampus of weanling female, but not male
      offspring (postnatal day, PND 21) of dams fed the low protein diet. The number of
      serotonergic cell bodies in the rostral raphe, and 5-HT metabolism in the limbic
      system of weanling offspring was not altered by maternal low protein diet. The
      deficit in hippocampal 5-HT1A receptor function observed in weanling female
      offspring persisted into adulthood (PND 112), and was accompanied by an increased
      sensitivity to stress, specifically increased immobility during a 15-minute
      forced swim challenge and increased anorexia following 30-minute restraint (PND
      97-100). The present work begins to uncover important future directions for
      understanding the early developmental origins of resilience to stress, and
      factors that may put individuals at greater risk for stress-related psychiatric
      disorders.

PMID- 29660441
TI  - Silencing the insular-striatal circuit decreases alcohol self-administration and
      increases sensitivity to alcohol.
AB  - Internal drug states/cues can impact drug taking, as pretreatment with a moderate
      to high alcohol dose (i.e., loading dose) can decrease subsequent alcohol self
      administration, alcohol-seeking, and relapse-like drinking. The insular cortex
      (IC) is implicated in processing information about internal states and findings
      show that silencing the IC and its projections to the nucleus accumbens core
      (AcbC) enhance sensitivity to the interoceptive effects of alcohol. Therefore,
      the goal of the present work was to determine the functional role of IC-AcbC
      projections in modulating the effects of alcohol pretreatment on operant alcohol
      self-administration. Long-Evans rats were trained to self-administer a sweetened
      alcohol solution (15% alcohol (v/v) + 2% sucrose (w/v)) and on test sessions
      received pretreatment with an alcohol loading dose. A chemogenetic strategy
      (i.e., hM4D Designer Receptors Exclusively Activated by Designer Drugs [DREADDs])
      was implemented to silence the IC-AcbC projections and test the functional role
      of the insular-striatal circuitry in regulating self-administration following the
      alcohol loading doses. Alcohol self-administration decreased following pre
      session treatment with alcohol, confirming titration of alcohol drinking
      following a loading dose of alcohol. Chemogenetic silencing of IC-AcbC
      projections decreased alcohol self-administration under baseline conditions
      (i.e., water loading dose) and the reduction in self-administration of an alcohol
      loading dose, implicating a role for this circuit in the maintenance of alcohol
      self-administration and suggesting increased sensitivity to the alcohol loading
      dose. These findings provide evidence for the critical nature of insular-striatal
      circuitry in ongoing alcohol self-administration, and specifically in relation to
      interoceptive/internal cues that can impact alcohol drinking.

PMID- 29660442
TI  - Biochemical and cognitive effects of docosahexaenoic acid differ in a
      developmental and SorLA dependent manner.
AB  - Beneficial effects of omega-3 fatty acid intake on cognition are under debate as
      some studies show beneficial effects while others show no effects of omega-3
      supplementation. These inconsistencies may be a result of inter-individual
      response variations, potentially caused by gene and diet interactions. SorLA is a
      multifunctional receptor involved in ligand trafficking including lipoprotein
      lipase and amyloid precursor protein. Decreased SorLA levels have been correlated
      to Alzheimer's disease, and omega-3 fatty acid supplementation is known to
      increase SorLA expression in neuronal cell lines and mouse models. We therefore
      addressed potential correlations between Sorl1 and dietary omega-3 in SorLA
      deficient mice (Sorl1-/-) and controls exposed to diets supplemented with or
      deprived of omega-3 during their entire development and lifespan (lifelong) or
      solely from the time of weaning (post weaning). Observed diet-induced effects
      were only evident when exposed to lifelong omega-3 supplementation or deprivation
      as opposed to post weaning exposure only. Lifelong exposure to omega-3
      supplementation resulted in impaired spatial learning in Sorl1-/- mice. The
      vitamin C antioxidant capacity in the brains of Sorl1-/- mice was reduced, but
      reduced glutathione and vitamin E levels were increased, leaving the overall
      antioxidant capacity of the brain inconclusive. No gross morphological
      differences of hippocampal neurons were found to account for the altered
      behavior. We found a significant adverse effect in cognitive performance by
      combining SorLA deficiency with lifelong exposure to omega-3. Our results stress
      the need for investigations of the underlying molecular mechanisms to clarify the
      precise circumstances under which omega-3 supplementation may be beneficial.

PMID- 29660443
TI  - Cell-to-cell Communication by Extracellular Vesicles: Focus on Microglia.
AB  - Extracellular vesicles, including exosomes and microvesicles, are small, nano-to
      micrometer vesicles that are released from cells. While initially observed in
      immune cells and reticulocytes as vesicles meant to remove archaic proteins, now
      they have been observed in almost all cell types of multicellular organisms.
      Growing evidence indicates that extracellular vesicles, containing lipids,
      proteins and RNAs, represent an efficient way to transfer functional cargoes from
      one cell to another. In the central nervous system, the extensive cross-talk
      ongoing between neurons and glia, including microglia, the immune cells of the
      brain, takes advantage of secreted vesicles, which mediate intercellular
      communication over long range distance. Recent literature supports a critical
      role for extracellular vesicles in mediating complex and coordinated
      communication among neurons, astrocytes and microglia, both in the healthy and in
      the diseased brain. In this review, we focus on the biogenesis and function of
      microglia-related extracellular vesicles and focus on their putative role in
      Alzheimer's disease pathology.

PMID- 29660445
TI  - Development of a new tool for the long term in vitro ecotoxicity testing of
      nanomaterials using a rainbow-trout cell line (RTL-W1).
AB  - The current wide use of manufactured nanomaterials (MNs) is leading to the
      release of nanoparticles (NPs) to water bodies. Aquatic organisms, including
      fish, are exposed to low concentrations of NPs for long periods of time being
      necessary to develop laboratory toxicity tests reflecting realistic conditions.
      Additionally, today there is a demand of in vitro assays respecting the 3Rs
      principle. Thus, the main aim of this work was to stablish an in vitro tool for
      the assessment of long-term NPs ecotoxicity. Considering the key role of liver in
      detoxification, a rainbow trout liver cell line, RTL-W1, was used. CuO NPs were
      chosen to validate this tool taking into account their important production
      level. Cells were exposed for 21 days to 25 or 100 MUg CuO NPs/ml. Every seven
      days cells were split and one fourth of them transferred to a new plate with
      appropriate concentrations of NPs in culture medium. Lower concentrations of CuO
      NPs did not cause any deleterious effect, whereas higher concentrations led to
      significant mortality after 14 days and to the intracellular accumulation of Cu
      particles. Identical results were observed in cells exposed to CuSO4 at the same
      Cu concentrations. Therefore, the observed toxic effects might be mainly due to
      Cu2+ ions.

PMID- 29660444
TI  - Ca2+-Binding Protein 1 Regulates Hippocampal-dependent Memory and Synaptic
      Plasticity.
AB  - Ca2+-binding protein 1 (CaBP1) is a Ca2+-sensing protein similar to calmodulin
      that potently regulates voltage-gated Ca2+ channels. Unlike calmodulin, however,
      CaBP1 is mainly expressed in neuronal cell-types and enriched in the hippocampus,
      where its function is unknown. Here, we investigated the role of CaBP1 in
      hippocampal-dependent behaviors using mice lacking expression of CaBP1 (C-KO). By
      western blot, the largest CaBP1 splice variant, caldendrin, was detected in
      hippocampal lysates from wild-type (WT) but not C-KO mice. Compared to WT mice, C
      KO mice exhibited mild deficits in spatial learning and memory in both the Barnes
      maze and in Morris water maze reversal learning. In contextual but not cued fear
      conditioning assays, C-KO mice showed greater freezing responses than WT mice. In
      addition, the number of adult-born neurons in the hippocampus of C-KO mice was
      ~40% of that in WT mice, as measured by bromodeoxyuridine labeling. Moreover,
      hippocampal long-term potentiation was significantly reduced in C-KO mice. We
      conclude that CaBP1 is required for cellular mechanisms underlying optimal
      encoding of hippocampal-dependent spatial and fear-related memories.

PMID- 29660446
TI  - A novel technique for ligation of the cephalic vein reduces hemorrhaging during a
      two-in-one insertion of dual cardiac device leads.
AB  - The cutdown technique for the cephalic vein is a common access route for
      transvenous cardiac device leads (TVLs), and sometimes one cephalic vein can
      accomodate two TVLs. We examined a novel ligation technique to balance the
      hemostasis and lead maneuverability for this two-in-one insertion. A total of 22
      patients scheduled for cardiac device implantations with two or more leads were
      enrolled. The ipsilateral cephalic vein was identified for inserting the TVLs
      with a cutdown. If two TVLs could be introduced into one cephalic vein,
      hemostasis was established by ligating the venous wall between the TVLs. We
      measured the amount of hemorrhaging per minute and the operators assessed the
      lead maneuverability before and after the ligation. We successfully implanted
      cardiac devices in 15 patients (68%) with this novel method, whereas only one TVL
      could be introduced via the cephalic vein in 7 patients. As for the successful
      patients, hemorrhaging from the gap was significantly reduced (5.6 +/- 7.3 to
      0.41 +/- 0.36g/min, p = 0.016) after the novel ligation. The lead maneuverability
      was well maintained so there was no difficulty placing the leads into the cardiac
      chambers in all cases. No major complications were observed. In the present
      study, the novel ligation method provided significant hemostasis as well as a
      preserved maneuverability. It could be an optional choice for insertion of
      multiple TVLs.

PMID- 29660447
TI  - The usefulness of ventricular pacing during atrial fibrillation ablation in a
      persistent left superior vena cava: A case report.
AB  - A 69-year-old woman with palpitations was referred to our hospital for a second
      session of atrial fibrillation (AF) catheter ablation. She had a history of AF
      ablation including pulmonary vein (PV) isolation and persistent left superior
      vena cava (PLSVC) isolation. Electrophysiologic studies showed the veno-atrial
      connections that had recovered. After PV isolation was performed, AF was induced
      by atrial premature contraction (APC) from the PLSVC, and AF storm occurred.
      During PLSVC isolation, AF was not induced by APC from the PLSVC. PLSVC isolation
      continued during sinus rhythm. The elimination of the PLSVC potential was
      difficult to confirm because of the far-field potential of the left ventricle.
      Then, we performed right ventricular pacing. The remaining PLSVC potential was
      identified. After that, the PLSVC isolation was successful during right
      ventricular pacing. Complications were not observed. The patient had no
      recurrence of AF thereafter.

PMID- 29660448
TI  - Nomenclature for factors of the HLA system, update February 2018.

PMID- 29660449
TI  - Nomenclature for factors of the HLA system, update January 2018.

PMID- 29660450
TI  - Nomenclature for factors of the HLA system, update March 2018.

PMID- 29660451
TI  - Does matching for SNPs in the MHC gamma block in 10/10 HLA-matched unrelated
      donor-recipient pairs undergoing allogeneic stem cell transplant improve
      outcomes?
AB  - BACKGROUND: Matching at the HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 loci is
      important in donor selection for patients undergoing unrelated allogeneic
      hematopoietic stem cell transplantation (ASCT). Additional matching across the
      MHC gamma region may further improve outcomes. METHODS: The MHC gamma region was
      retrospectively genotyped in 66 adult recipients of ASCT and their 10/10 matched
      unrelated donors. A chart review was performed to determine whether MHC gamma
      matching impacted survival, relapse, or graft-versus-host disease. RESULTS: Of 66
      donor-recipient pairs, 26(39.4%) were gamma-type matches, 34(51.5%) were
      mismatches, and 6(9.1%) were "indeterminate." Matching status was not associated
      with overall survival (p = 0.43), relapse (p = 0.21), acute GVHD (p = 0.43),
      severe aGVHD (p = 0.31), or chronic GVHD (p = 0.23) in univariate analyses, nor
      in multivariate analyses (p = 0.28, 0.13, 0.29, 0.16, and 0.67, respectively),
      with or without adjusting for HLA-DPB1 matching status. CONCLUSIONS: In our
      single institution study, gamma-type matching status was not associated with
      outcomes of adult ASCT recipients.

PMID- 29660452
TI  - Simulation of non-inherited maternal antigens acceptable HLA mismatches to
      increase the chance of matched cord blood units: Hong Kong's experience.
AB  - In Cord blood transplantation (CBT), the non-inherited maternal antigen (NIMA)
      virtual six HLA matched CB is found to have similar outcomes to six HLA inherited
      matched CB. Such virtual HLA matched CB units can be generated by substituting
      the inherited alleles with one to three NIMAs. In Hong Kong Cord Blood Bank, CB
      units have no NIMA defined. 100 CB samples were collected with NIMA defined.
      Retrospective searches of Hong Kong patients (n = 520) were matched against the
      inherited and virtual HLA phenotypes of NIMA CB file. One to three NIMA matches
      was analyzed, virtual six HLA matches were identified for 31.7% patients, 29.4%
      from CB units with 5/6 HLA match with 1 NIMA match and 1.7% CB units with a 4/6
      HLA match and 2 NIMA matches. However, searches in the 167,201 Bone Marrow Donors
      Worldwide CB units with defined NIMA did not yield similar increases, possibly
      due to the ethnicity differences between populations. The match performance rises
      from 26% to 60% after including the NIMA match. Comparing the match performance
      of 32% in a previous Dutch study, we calculated with 60% matching in this smaller
      size study. This provides a solid ground to considering NIMA in stem cell donor
      selection which was adopted in some centers, to be extended to Asian and local CB
      registries to increase the chance for matches and also to improve patient
      outcomes, increase the utilization of CB units, enhance clinical flexibility and
      signify economic intelligence.

PMID- 29660453
TI  - TGF-beta1 down-regulation in the mediobasal hypothalamus attenuates hypothalamic
      inflammation and protects against diet-induced obesity.
AB  - BACKGROUND: The consumption of large amounts of dietary fats induces hypothalamic
      inflammation and impairs the function of the melanocortin system, leading to a
      defective regulation of caloric intake and whole-body energy expenditure. In mice
      fed a high-fat diet (HFD), TGF-beta1 expression was increased and NF-kappaB
      signaling was activated in proopiomelanocortin neurons, which plays an important
      role in the obesity-associated hypothalamic inflammation scenario. However,
      whether excessive hypothalamic TGF-beta1 impairs energy homeostasis remains
      unclear. OBJECTIVES: We aimed to investigate the role of diet-induced
      hypothalamic TGF-beta1 on inflammation and whole-body energy homeostasis.
      METHODS: A TGF-beta1 inhibitory lentiviral shRNA particle was stereotaxically
      injected bilaterally in the arcuate nucleus (ARC) of C57BL/6 mice fed a HFD. We
      assessed changes in body mass and adiposity, food intake, inflammatory markers,
      and the function of energy and glucose metabolism. RESULTS: TGF-beta1 down
      regulation in the ARC-attenuated body-mass gain, reduced fat-mass accumulation,
      decreased hypothalamic inflammatory markers, and protected against HFD-induced
      lipohypertrophy of brown adipose tissue. In addition, the inhibition of
      hypothalamic TGF-beta1 increased the locomotor activity and improved whole-body
      lipid metabolism, which attenuated hepatic fat accumulation and serum
      triglyceride levels. No changes were observed in food intake and glucose
      homeostasis. CONCLUSION: Hypothalamic TGF-beta1 down-regulation attenuates
      hypothalamic inflammation and improves energy metabolism, resulting in lower body
      mass gain and lower fat-mass accumulation, which protects mice from the
      development of obesity. Our data suggest that modulation of hypothalamic TGF
      beta1 expression might be an effective strategy to treat obesity.

PMID- 29660455
TI  - Purification, characterization and antioxidant activity of the exopolysaccharide
      from Weissella cibaria SJ14 isolated from Sichuan paocai.
AB  - In the present study, an exopolysaccharide (EPS)-producing strain SJ14 isolated
      from Sichuan paocai was identified as Weissella cibaria, with a typical ropy
      phenotype. W. cibaria SJ14 possessed good capabilities of acid production, salt
      tolerance, and nitrite depletion. The crude polysaccharides were obtained from
      the culture supernatant of strain SJ14 and further fractionated by DEAE-Sepharose
      Fast Flow ion-exchange and Sephadex G-100 size-exclusion chromatography.
      Consequently, two acidic EPS fractions (EPS-1 and EPS-3) were obtained with the
      average molecular weights of 7.12 * 104 and 3.01 * 104 Da, respectively. They
      were heteropolysaccharides, among which EPS-1 were rich in mannose, and composed
      of mannose, glucose, galactose, arabinose, xylose, and rhamnose in a molar ratio
      of 23.79: 4.80: 1.66: 1.00: 0.21: 0.09, whereas EPS-3 consisted of galactose,
      mannose, glucose, and arabinose in a molar ratio of 7.47: 3.69: 1.00: 0.85 were
      rich in galactose. Two EPS fractions also exhibited potential antioxidant
      properties in vitro, showing strong scavenging activities on three kinds of free
      radicals and reducing power, and the antioxidant activities of EPS-1 were
      significantly stronger than that of EPS-3.

PMID- 29660454
TI  - Purification and structural elucidation of a water-soluble polysaccharide from
      the fruiting bodies of the Grifola frondosa.
AB  - Grifola frondosa is a polypore mushroom, which has been used for many centuries
      by traditional Chinese and Japanese herbalists as a medicinal mushroom. A water
      soluble polysaccharide (code as GFP30-2-a, molecular weight: 2.04*106Da) was
      isolated from the fruiting bodies of G. frondosa by hot water extraction, ethanol
      precipitation and chromatography. Its structure was elucidated from its
      monosaccharide composition, methylation analysis, together with 1D NMR (1H NMR
      and 13C NMR) and 2D NMR (COSY, TOCSY, HSQC, HMBC and NOESY spectra). GFP30-2-a
      consists of D-Glc and D-Gal in the molar ratio of 1:0.098 and the structure of
      the repeating units was identified to be beta-d-Glcp-(1->[4)-alpha-d-Glcp-(1->4)
      alpha-d-Glcp-(1]m->4)-alpha-d-Glcp.

PMID- 29660456
TI  - Chitosan-based hydrogels: Preparation, properties and applications.
AB  - Chitosan (CS), the second most plentiful natural polysaccharide next to
      cellulose, has valuable characteristics including biocompatibility, nontoxicity
      and biodegradability. CS is broken down in the human body to innocuous products
      (amino sugars). Hydrogels are polymeric materials with three dimensional networks
      retaining a huge quantity of water within their structures which are of great
      interest in biomedical/environmental applications. Usually, injectable hydrogels
      have functional groups which are sensitive to pH, temperature or irradiation
      stimuli. Injectable scaffolds can be formed in situ through stimuli-responsive
      effect and they can overcome the drawback of traditional scaffolds which require
      surgery in order to be placed on the desired tissue. The antibacterial/antifungal
      activities of chitosan-based hydrogels and their applications in controlled drug
      delivery/release systems, tissue engineering, preparation of injectable hydrogels
      and water treatment (removal of heavy/toxic metals and dyes) will be described.
      Moreover, the molecular dynamics (MD) simulation were performed on the delivery
      of the anticancer chlorambucil (CB) drug using three silica filled polymeric
      nanocomposites based on chitosan (CS), polylactic acid (PLA) and polyethylene
      glycol (PEG) and it was illustrated that among three drug delivery systems
      (DDSs), the CS nanocomposite was the most efficient DDS due to the lowest drug
      diffusion was measured for the CS system that could lead to the most
      sustained/controlled drug delivery.

PMID- 29660457
TI  - A lectin fraction from green seaweed Caulerpa cupressoides inhibits inflammatory
      nociception in the temporomandibular joint of rats dependent from peripheral
      mechanisms.
AB  - Temporomandibular disorders are the second most common cause of orofacial pain
      mediated by inflammatory compounds, which in many cases leads to chronic
      orofacial pain. This study assessed the antinociceptive and anti-inflammatory
      effects of a lectin from the green seaweed Caulerpa cupressoides (CcL) on
      hypernociception inflammatory in TMJ of rats and investigated the involvement of
      different mechanisms. Rats received i.v. CcL 30 min prior to injection of
      flogistic agentes or 0.9% saline into the left TMJ. Pretreatment with CcL (0. 1;
      1 or 10 mg/kg) promoted a reduction (p < 0.05) of inflammatory hypernociception
      induced by 1.5% Formalin along with inhibition of inflammatory plasma
      extravasation, cytokines levels, ciclooxigenase-2, and intercellular adhesion
      molecule (ICAM-1). CcL was able to inhibit the nociceptive response induced by
      1.5% Capsaicin, suggesting that CcL has an antinociceptive effect, acting
      directly on the primary nociceptive neurons. CcL also inhibited the nociceptive
      response induced by Carrageenan (100 MUg/TMJ) or Serotonin (5-HT) (225 MUg/TMJ).
      In conclusion, the results demonstrate that administration of CcL has a potential
      antinociceptive and anti-inflammatory effect, with a mechanism that is partially
      dependent on TNF-alpha, IL-1beta, COX-2 and ICAM-1 inhibition and independently
      from the cannabinoide and opioid system and NO/cGMP/PKG/K+ATP channel pathway.

PMID- 29660458
TI  - An easily recoverable and highly reproducible agar-supported palladium catalyst
      for Suzuki-Miyaura coupling reactions and reduction of o-nitroaniline.
AB  - Polysaccharides are excellent support materials for catalytic systems due to
      their superior metal binding capacity, high mechanical strength, and green
      nature. Among the polysaccharides, agar can be considered a good support material
      for catalytic reactions from the point of its low cost, easy availability, high
      thermal durability, and biodegradability. In this study, agar-supported palladium
      catalyst (AG-Pd) was designed for the first time, and then its catalytic
      performance was tested towards (i) Suzuki-Miyaura coupling reactions and (ii)
      catalytic reduction of o-nitroaniline to o-phenylenediamine under mild reaction
      conditions. Additionally, the reproducibility of the designed AG-Pd catalyst was
      investigated in both catalytic reactions, and the tests showed that the catalyst
      could be reused many times. AG-Pd catalyst displayed excellent selectivity and
      efficiency in Suzuki-Miyaura coupling reactions in only 6 min under solvent-free
      media. In addition, AG-Pd catalyst provided good catalytic reduction by
      completely reducing o-nitroaniline in 90 s at room temperature. These findings
      reveal that agar is a good support material, and it can be used for different
      catalytic systems as a support.

PMID- 29660459
TI  - Investigation on the behavior of collagen self-assembly in vitro via adding
      sodium silicate.
AB  - Silicon, a trace element found in human body, plays a critical role in the
      process of collagen self-assembly. In this study, the intermolecular interaction
      and fibrillogenesis process were investigated to understand the effects of
      various concentrations of sodium silicate (SS) on collagen self-assembly in
      vitro. Fourier transform infrared spectroscopy analysis indicated that the triple
      helical structure of collagen was not significantly affected by SS. Hydrophobic
      interactions and particle sizes of collagen aggregates, which were measured using
      pyrene fluorescence and dynamic light scanning, enhanced via adding 2 mM SS
      whereas decreased with further increasing concentrations (4-8 mM). Kinetic
      analysis revealed that an increase in hydrophobic interactions boosted collagen
      self-assembly in the presence of 2 mM SS. The inhibition of self-assembly with
      the addition of 4-8 mM SS, as illustrated by a reduction in the fibrillogenesis
      rate and turbidity, was potentially attributed to weak hydrophobic interactions
      and strong electrostatic repulsion. The observation of microscopy demonstrated
      that the fibrils exhibited the characteristic D-periodicity at 2 mM SS. The
      inhibitory effect of 4 mM SS was slight and the fibrils still formed, while the
      microstructure was consisted of clustered collagen aggregates as SS >= 6 mM owing
      to serious inhibition on collagen self-assembly.

PMID- 29660460
TI  - Influences of modified bacterial cellulose nanofibers (BCNs) on structural,
      thermophysical, optical, and barrier properties of poly ethylene-co-vinyl acetate
      (EVA) nanocomposite.
AB  - The BCNs were chemically modified using acetic anhydride with the aim of
      improving its dispersion and interfacial adhesion. Acetylation of BCNs was
      confirmed by FT-IR spectroscopy. Morphology studies using TEM and SEM revealed
      that a reasonable dispersion of the modified BCNs in the EVA matrix was
      accomplished. The DSC data displayed a little shift in the Tg to higher
      temperatures with the incorporation of both modified and unmodified BCNs.
      Increased thermal stability of the nanocomposites consisting acetylated BCNs was
      confirmed by TGA technique. DMA measurements highlighted that the storage modulus
      increased and the damping properties decreased for the nanocomposites with regard
      to the neat EVA.

PMID- 29660461
TI  - Biodegradable kappa-carrageenan/nanoclay nanocomposite films containing
      Rosmarinus officinalis L. extract for improved strength and antibacterial
      performance.
AB  - In this study, biodegradable kappa-carrageenan films containing 3% nanoclay and
      different amounts of rosemary extract (1, 2 and 3% v/v) were fabricated and their
      physical, thermal, and mechanical properties, as well as antimicrobial activity
      were examined. The film thickness did not change significantly by the addition of
      rosemary extract. UV light transmission value in the control film was 20.46%,
      while the value for the film with 3% v/v rosmary extract reduced to 0.13%.
      Elongation at break (EB%) and tensile strength (TS) of the carrageenan film
      without the extract were 19.07% and 15.96MPa, respectively, while after adding 3%
      v/v of rosemary extract, the EB and TS were increased to 27.17% and 30.77MPa,
      respectively. Incorporation of rosemary extract greatly reduced water vapor
      permeability (WVP) (5.27*10-10g/m.s.Pa in control film vs 2.14*10-10g/m.s.Pa in
      the film containing 3% v/v rosemary extract). More importantly, the carrageenan
      film with 3% extract displayed >99% inhibition against B. cereus, E. coli, P.
      aeruginosa, and S. aureus compared with the control film. The present study
      showed that rosemary extract is an excellent additive to enhance the mechanical
      strength and antibacterial activity of carrageenan films and can be used for
      active packing in food packing industry.

PMID- 29660462
TI  - Anti-Helicobacterpylori effectiveness and targeted delivery performance of
      amoxicillin-UCCs-2/TPP nanoparticles based on ureido-modified chitosan
      derivative.
AB  - The amoxicillin-UCCs-2/TPP nanoparticles constructed with ureido-modified
      chitosan derivative UCCs-2 and sodium tripolyphosphate (TPP) played an important
      role to deliver drug to achieve more efficacious and specific eradication of
      Helicobacterpylori (H. pylori) in vitro. In this study, the anti-H. pylori
      effectiveness in vivo and uptake mechanism was investigated in details, including
      the effect of temperature, pH values and the addition of competitive substrate
      urea on uptake. Compared with unmodified nanoparticles, a more efficacious and
      specific anti-H. pylori activities were obtained in vivo by using this biological
      chitosan derivative UCCs-2. Histological staining and immunological analysis
      verified that the amoxicillin-UCCs-2/TPP nanoparticles could diminish the
      proinflammatory cytokines levels and alleviate the inflammatory damages caused by
      H. pylori infection. The uredio-modified nanoparticles also have favorable
      gastric retention property, which is beneficial for the oral drug delivery to
      targeted eradicate H. pylori infection in stomach. These findings suggest that
      this targeted drug delivery system may serve for specific treatment of H. pylori
      infection both in vitro and in vivo, which can also be used as promising
      nanocarriers for other therapeutic reagents to target H. pylori.

PMID- 29660463
TI  - Liposomal CpG-ODN: An in vitro and in vivo study on macrophage subtypes
      responses, biodistribution and subsequent therapeutic efficacy in mice models of
      cancers.
AB  - CpG oligodeoxynucleotides (CpG-ODN), a common immune stimulator and vaccine
      adjuvant, was reported to switch Tumor Associated Macrophages (TAMs) from M2 to
      M1 phenotype inducing anti-tumor responses. Liposomes are of the successfully
      applied carriers for CpG-ODN. The aim of present study was design and preparation
      of a liposomal formulation containing phosphodiester CpG-ODN, evaluation of its
      effect on macrophages responses, and subsequent antitumor responses in mice.
      Liposomal formulations containing phosphodiester CpG-ODN or non-CpG-ODN were
      prepared and characterized. MTT reduction assay in four different cell lines,
      uptake, arginase and iNOS activity evaluation in macrophage cell lines,
      biodistribution study and therapeutic anti-tumor effects of formulations in mice
      bearing C26 colon carcinoma or B16F0 melanoma were carried out. The size of
      liposomes containing CpG-ODN was ~200 nm with the encapsulation efficiency of
      33%. The iNOS activity assay showed high nitric oxide (NO) level in M2 phenotype
      of macrophage cell lines treated by liposomes containing CpG-ODN. In mice which
      received liposomes containing CpG-ODN as a monotherapy, maximum tumor growth
      delay with remarkable survival improvement was observed compared to control
      groups. Biodistribution study showed the accumulation of liposomal formulation in
      tumor micro-environment. In conclusion, considerable anti-tumor responses
      observed by liposomes containing CpG-ODN was due to enhanced delivery of CpG-ODN
      to immune cells and subsequent initiation of anti-tumoral immune responses.

PMID- 29660464
TI  - Drug permeability profiling using cell-free permeation tools: Overview and
      applications.
AB  - Cell-free permeation systems are gaining interest in drug discovery and
      development as tools to obtain a reliable prediction of passive intestinal
      absorption without the disadvantages associated with cell- or tissue-based
      permeability profiling. Depending on the composition of the barrier, cell-free
      permeation systems are classified into two classes including (i) biomimetic
      barriers which are constructed from (phospho)lipids and (ii) non-biomimetic
      barriers containing dialysis membranes. This review provides an overview of the
      currently available cell-free permeation systems including Parallel Artificial
      Membrane Permeability Assay (PAMPA), Phospholipid Vesicle-based Permeation Assay
      (PVPA), Permeapad(r), and artificial membrane based systems (e.g. the artificial
      membrane insert system (AMI-system)) in terms of their barrier composition as
      well as their predictive capacity in relation to well-characterized intestinal
      permeation systems. Given the potential loss of integrity of cell-based
      permeation barriers in the presence of food components or pharmaceutical
      excipients, the superior robustness of cell-free barriers makes them suitable for
      the combined dissolution/permeation evaluation of formulations. While cell-free
      permeation systems are mostly applied for exploring intestinal absorption, they
      can also be used to evaluate non-oral drug delivery by adjusting the composition
      of the membrane.

PMID- 29660465
TI  - Jageum-Jung improves 2,4-dinitrochlorobenzene-induced atopic dermatitis-like skin
      lesions in mice and suppresses pro-inflammatory chemokine production by
      inhibiting TNF-alpha/IFN-gamma-induced STAT-1 and NFkappaB signaling in HaCaT
      cells.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Jageum-Jung (JGJ) is an oriental herbal formula
      comprising five herbs (Melaphis chinensis Bell, Cremastra variabilis Nakai,
      Knoxia valerianoides Thorel, Euphorbia lathyris L., and Moschus moschiferus L.).
      It has been used for detoxification and treating cancer and inflammatory diseases
      in China, Japan, and Korea. However, the mechanism of action of JGJ on
      keratinocyte inflammatory response is poorly understood. AIM OF THE STUDY: In the
      present study, we investigated the anti-inflammatory mechanism of JGJ and studied
      the effects of JGJ on atopic dermatitis-like skin lesions in mice. MATERIALS AND
      METHODS: We elucidated the anti-inflammatory and anti-inflammatory effects of JGJ
      on tumor necrosis factor-alpha/interferon-gamma (TNF-alpha/IFN-gamma)-treated
      human keratinocyte cells, IgE-sensitized RBL-2H3 cells, and 2,4
      dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD)-like mice,
      respectively. RESULTS: The results showed that JGJ suppressed the production and
      mRNA revels of IL-8, IL-6 and, conspicuously, both TARC and RANTES. JGJ inhibited
      nuclear translocation of the inflammatory transcription factors NFkappaB and STAT
      1. Moreover, JGJ improved AD-like skin lesions in DNCB-treated mice and inhibited
      degranulation of mast cell. CONCLUSIONS: The results of this study suggest that
      JGJ can be considered as a candidate agent for AD treatment.

PMID- 29660466
TI  - Formononetin, an isoflavone from Astragalus membranaceus inhibits proliferation
      and metastasis of ovarian cancer cells.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Astragalus membranaceus which was originally
      described in the Shennong's Classic of Materia Medica, the earliest complete
      Pharmacopoeia of China written from the Warring States Period to Han Dynasty, has
      been widely used in Chinese medicine for > 2000 years, especially in the
      prescription of curing cancer. A. membranaceus has various bioactivities, such as
      anti-tumor, anti-viral, anti-oxidant, anti-diabetes, anti-inflammation, anti
      atherosclerosis, immunomodulation, hepatoprotection, hematopoiesis,
      neuroprotection and so on. As an important component of A. membranaceus, whether
      formononetin has a close relationship with its tumor-inhibiting effect on ovarian
      cancer cell has been investigated. AIM OF STUDY: The present study aimed to
      demonstrate the anti-proliferation, anti- migration and invasion effects of
      formononetin on ovarian cancer cells and further explore the underlying molecular
      mechanisms associated with apoptosis, migration and invasion. MATERIALS AND
      METHODS: MTT assay was performed to detect the viability of ovarian cancer cells.
      DAPI staining, Annexin-V assay and assay for mitochondrial membrane potential
      detected the apoptosis of ovarian cancer cells treated by formononetin. The
      migration and invasion of ovarian cancer cells which exposed to formononetin were
      detected by scratch assay and transwell assay. Meanwhile, the protein-level
      changes of in ovarian cancer cells treated by formononetin were assessed by
      western blot analysis. RESULTS: MTT assays indicated that cell viability
      significantly decreased in ovarian cancer cells treated with formononetin. DAPI
      staining, Annexin-V assay and assay for mitochondrial membrane potential
      suggested that formononetin suppressed cells proliferation by inducing apoptosis.
      We detected the expression of apoptosis-related proteins in ovarian cancer cells
      after treatment with formononetin and found the expression of caspase 3/9
      proteins and the ratio of Bax/Bcl-2 were increased in a dose-dependent manner. In
      addition, wound healing and transwell chamber assays showed that formononetin
      suppressed the migration and invasion of ovarian cancer cells. And formononetin
      decreased expression of MMP-2/9 proteins and phosphorylation level of ERK.
      CONCLUSIONS: The present results demonstrated that formononetin have potential
      effects on induction of apoptosis and suppression of migration and invasion.

PMID- 29660467
TI  - Investigation of constituents from Cinnamomum camphora (L.) J. Presl and
      evaluation of their anti-inflammatory properties in lipopolysaccharide-stimulated
      RAW 264.7 macrophages.
AB  - ETHNOPHARMACOLOGY RELEVANCE: Cinnamomum camphora (L.) J. Presl has been used for
      the traditional medicine as a therapeutic agent of inflammation-related diseases,
      including sprains, rheumatic arthritis, abdominal pain, cough and bronchitis, for
      a long history. The aim of the present study was to illustrate anti-inflammatory
      substances of C. camphora and their mechanism of action, and to establish the
      correlations between chemical constituents and traditional uses of this plant.
      MATERIALS AND METHODS: Chemical constituents were purified by chromatographic
      methods, and their structures were established based on spectroscopic analysis.
      Lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages was adopted for
      evaluating the anti-inflammatory activity in vitro. The nitric oxide (NO)
      production assay and nuclear factor kappa B (NF-kappaB) dual luciferase reporter
      assay were used to screen anti-inflammatory constituents. The mRNA and protein
      levels of inflammation-related cytokines and enzymes were determined by real-time
      reverse transcription-polymerase chain reaction (RT-PCR), immunoblot analysis,
      and enzyme linked immunosorbent assay (ELISA), respectively. RESULTS: Twenty-five
      constituents were isolated from the EtOH extract of C. camphora. Eight
      constituents, covering phenylpropanoid (7), lignans (10 and 22), flavonoids (16
      18), coumarin (21), and terpenoid (24) significantly inhibited LPS-stimulated NO
      production with maximum inhibition rates (MIRs) of >= 80%, and thus were verified
      to be the anti-inflammatory substances of this ethnomedical plant. (+)
      Episesaminone (SMO, 22) and 3S-(+)-9-oxonerolidol (NLD, 24) blocked NF-kappaB
      activation via inducing IkappaBalpha expression. Moreover, SMO and NLD inhibited
      productions of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and
      prostaglandin E2 (PGE2), and alleviated increased mRNA and protein levels of
      inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), and matrix
      metallopeptidase-9 (MMP-9) in LPS-stimulated RAW 264.7 macrophages. CONCLUSIONS:
      The ethnomedical use of C. camphora for the treatment of inflammation-related
      diseases was attributed to the combined in vitro anti-inflammatory activities of
      phenylpropanoid, lignan, flavonoid, coumarin, and terpenoid. SMO and NLD were
      found to be new molecules with in vitro anti-inflammatory activities, which are
      achieved by inhibiting NF-kappaB regulated inflammatory response.

PMID- 29660469
TI  - Dothiorelone derivatives from an endophyte Diaporthe pseudomangiferaea inhibit
      the activation of human lung fibroblasts MRC-5 cells.
AB  - Nine new compounds (1-6 and 16-18) and nine known compounds (7-15) were isolated
      from Diaporthe pseudomangiferaea, an endophytic fungus obtained from the leaves
      of the toxic Chinese folk medicine Tylophora ouata. Their structures were
      elucidated by NMR spectroscopy and MS spectrometry analyses. The absolute
      configurations were established according to the specific rotation or electron
      circular dichroism method. Compounds 1, 4, 9, 11, 14 and 15 inhibited the TFG
      beta induced activation of human lung fibroblasts MRC-5 cells by 17.4%, 59.2%,
      62.9%, 41.1%, 32.9% and 52.1% at 10 MUM, respectively, while positive control
      pirfenidone showed 53.2% inhibition rate at 1 mM. The MTT assay showed that
      compounds 13 and 14 displayed cytotoxicity against BGC-823 cells, with IC50
      values of 8.1 and 4.4 MUM, respectively.

PMID- 29660468
TI  - Ethyl-acetate fraction of Trichilia catigua protects against oxidative stress and
      neuroinflammation after cerebral ischemia/reperfusion.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Trichilia catigua A. Juss (Meliaceae)
      preparations have been used in folk medicine to alleviate fatigue, stress, and
      improve memory. Antinociceptive, antiinflammatory, and in vitro neuroprotective
      effects have been observed in animals. Cerebral ischemia/reperfusion (I/R) leads
      to severe neuropsychological deficits that are largely associated with oxidative
      stress, inflammation and neurodegeneration. We reported previously that an ethyl
      acetate fraction (EAF) of T. catigua reduced brain ischemia-induced learning and
      memory impairments in the absence of histological protection. AIM OF THE STUDY:
      Continuing those studies, here we aimed to investigate the antioxidant and
      antiinflammatory properties of T. catigua in an in vivo model of I/R. MATERIAL
      AND METHODS: Rats were subjected to 15 min of brain ischemia (4-VO model)
      followed by up to 15 days of reperfusion. Vehicle was given by gavage 30 min
      before ischemia and at 1 h of reperfusion. In a first experiment, brain ischemia
      induced changes in oxidative stress markers, i.e., reduced glutathione (GSH),
      oxidized glutathione (GSSG), superoxide dismutase (SOD), catalase (CAT),
      malondialdehyde (MDA), and protein carbonyl groups (PCGs) were measured on days
      1, 3, and 5 post-ischemia. Similar time course analysis was done for
      neuroinflammation markers, i.e., microglia (OX42 immunorreactivity) and
      astrocytes (GFAP immunorreactivity), in the hippocampus. In a second experiment,
      the time points at which these markers of oxidative stress and neuroinflammation
      peaked were used to test the effects of T. catigua (400 mg/kg, p.o.). RESULTS:
      Oxidative stress markers peaked on day 1 post-ischemia. GSH decreased (-23.2%)
      while GSSG increased (+ 71.1%), which yielded a significant reduction in the
      GSH/GSSG ratio (-39.1%). The activity of CAT was largely reduced by ischemia (
      54.6% to -65.1%), while the concentration of PCG almost doubled in the brain of
      ischemic rats (+99.10%) in comparison to sham. Treatment with the EAF of T.
      catigua normalized these changes in oxidative markers to the control levels (GSH:
      +27.5%; GSSG: -23.8%; GSH/GSSG: +44.6%; PCG: -80.3%). In the hippocampus,
      neuroinflammation markers peaked on day 5 post-ischemia, with microglial and
      astrocytic responses increasing to 54.8% and 37.1%, respectively. The elevation
      in glial cells response was completely prevented by EAF. CONCLUSION: These
      results demonstrate that T. catigua has both antioxidant and antiinflammatory
      activities after transient global cerebral ischemia in rats, which may contribute
      to the previously reported memory protective effect of T. catigua.

PMID- 29660470
TI  - The effects of starvation and acidification on lag phase duration of surviving
      yeast cells.
AB  - Starvation is one of the most common forms of stress experienced in the wild
      life. Such conditions associate the other forms of stress such as acid, heat,
      oxidation, and so on. Organisms acclimate to such stresses and acquire the stress
      tolerances, which often trade-off their growth rates. To investigate whether
      starvation and the associated stresses may cause the changes in the growth and
      the central carbon metabolism, we stock-cultured the yeast S. cerevisiae on YNB
      agar plates up to a month and subsequently cultured in YNB broth. The pH of the
      agar medium just under the yeast's colonies sharply dropped from 5.0 to 3.9 in
      the first day, eventually reached approximately 3.0, and the viability
      logarithmically decreased. The surviving cells accumulated cell damages that were
      measured as the prolonged LPDs (lag phase durations). We did not, however,
      observe the effects of long-term stock-cultivations on the measured phenotypes:
      growth rates, the carrying capacities, and the glycolytic oscillations that are
      the temporal dynamics of the central carbon metabolism. Our study revealed that
      the contribution of cell damages to the total delay in growth was 78%, and that
      LPDs are closely related to damage-recovery mechanisms.

PMID- 29660471
TI  - Efficient production of human goose-type lysozyme 2 in the methylotrophic yeast
      Pichia pastoris.
AB  - Infectious diseases caused by antibiotic multidrug-resistant microorganisms are
      major causes of morbidity and mortality in humans. Hence, there is an urgent need
      to search for new antimicrobial agents. Initially known as a defensive effector
      in the innate immunity of certain organs of the human body, human goose-type
      lysozyme 2 (hLysG2) has been shown to possess therapeutically useful potential
      against multidrug-resistant microorganisms. Developing a novel strategy for large
      scale production that provides high yields of this protein with high purity,
      quality, and potency is critical for pharmaceutical applications. To overcome the
      issues related to prokaryotic expression, here we report the production of
      recombinant hLysG2 (rhLysG2) using the methylotrophic yeast Pichia pastoris as
      expression host. The strong inducible alcoholoxidase 1 (AOX1) promoter was used
      to drive expression of the optimized hLysG2 gene. Under the optimal expression
      conditions, the lytic activity of rhLysG2 reached 113 U/mL of culture supernatant
      in shake flask cultivation and this was increased to 2084 U/mL in fed-batch
      fermentation. Using chitin affinity chromatography and size-exclusion
      chromatography, rhLysG2 was produced with a yield of 137 mg/L, purity of > 99%,
      molecular weight of 21,504.6 Da, and specific activity of 13,500 U/mg. In vitro
      assays indicated that rhLysG2 possessed muramidase activity, isopeptidase
      activity, and free radical scavenging activity. This report describes an
      efficient strategy for the production of biologically active rhLysG2 in P.
      pastoris on a large scale with a high yield, which provides a solid foundation
      for possible future pharmaceutical applications.

PMID- 29660472
TI  - Enhanced cellobiose fermentation by engineered Saccharomyces cerevisiae
      expressing a mutant cellodextrin facilitator and cellobiose phosphorylase.
AB  - To efficiently ferment intermediate cellodextrins released during cellulose
      hydrolysis, Saccharomyces cerevisiae has been engineered by introduction of a
      heterologous cellodextrin utilizing pathway consisting of a cellodextrin
      transporter and either an intracellular beta-glucosidase or a cellobiose
      phosphorylase. Among two types of cellodextrin transporters, the passive
      facilitator CDT-2 has not enabled better cellobiose fermentation than the active
      transporter CDT-1, which suggests that the CDT-2 might be engineered to provide
      energetic benefits over the active transporter in cellobiose fermentation. We
      attempted to improve cellobiose transporting activity of CDT-2 through laboratory
      evolution. Nine rounds of a serial subculture of S. cerevisiae expressing CDT-2
      and cellobiose phosphorylase on cellobiose led to the isolation of an evolved
      strain capable of fermenting cellobiose to ethanol 10-fold faster than the
      original strain. After sequence analysis of the isolated CDT-2, a single point
      mutation on CDT-2 (N306I) was revealed to be responsible for enhanced cellobiose
      fermentation. Also, the engineered strain expressing the mutant CDT-2 with
      cellobiose phosphorylase showed a higher ethanol yield than the engineered strain
      expressing CDT-1 and intracellular beta-glucosidase under anaerobic conditions,
      suggesting that CDT-2 coupled with cellobiose phosphorylase may be better choices
      for efficient production of cellulosic ethanol with the engineered yeast.

PMID- 29660473
TI  - Increasing thermal stability of glutamate decarboxylase from Escherichia. coli by
      site-directed saturation mutagenesis and its application in GABA production.
AB  - Gamma-amino butyric acid (GABA) is an important bio-product used in
      pharmaceuticals, functional foods, and a precursor of the biodegradable plastic
      polyamide 4 (Nylon 4). Glutamate decarboxylase B (GadB) from Escherichia. coli is
      a highly active biocatalyst that can convert l-glutamate to GABA. However, its
      practical application is limited by the poor thermostability and only active
      under acidic conditions of GadB. In this study, we performed site-directed
      saturation mutagenesis of the N-terminal residues of GadB from Escherichia coli
      to improve its thermostability. A triple mutant (M6, Gln5Ile/Val6Asp/Thr7Gln)
      showed higher thermostability, with a 5.6 times (560%) increase in half-life
      value at 45  degrees C, 8.7  degrees C rise in melting temperature (Tm) and a
      14.3  degrees C rise in the temperature at which 50% of the initial activity
      remained after 15 min incubation (T1550), compared to wild-type enzyme. Protein
      3D structure analysis showed that the induced new hydrogen bonds in the same
      polypeptide chain or between polypeptide chains in E. coli GadB homo-hexamer may
      be responsible for the improved thermostability. Increased thermostability
      contributed to increased GABA conversion ability. After 12 h conversion of 3
      mol/L l-glutamate, GABA produced and mole conversion rate catalyzed by M6 whole
      cells was 297 g/L and 95%, respectively, while those by wild-type GAD was 273.5
      g/L and 86.2%, respectively.

PMID- 29660474
TI  - Decarboxylation of indomethacin induced by heat treatment.
AB  - As crystalline indomethacin is heated and subsequently cooled, it transforms into
      glassy indomethacin. While the original crystals are off-white in color, the
      glass becomes blackish-brown via a yellow intermediate stage. TLC of the
      components of the glass revealed three bands. The yellow component, which is
      generated either under hypoxic conditions or in the dark, was elucidated by NMR
      spectroscopy to be a decarboxylated fragment produced by thermal degradation. The
      colorless component is proposed to be formed by the opening of the indole ring of
      indomethacin; the structure of this degradation product was identified by EI-MS
      to be the same as the oxidative-cleavage product formed upon UV-irradiation, as
      previously reported. Another band was a blackish-brown pigment whose mobility
      placed it close to the TLC baseline. This oxidative-cleavage product and the
      blackish-brown pigment are not generated under hypoxic conditions. However, the
      extent of indomethacin decarboxylation under hypoxic conditions was found to be
      dependent on the heating temperature and time. Consequently, we prepared
      amorphous indomethacin through control of the heating temperature and time;
      heating at 160  degrees C for 30 min or less under hypoxic conditions is optimum
      for obtaining pure amorphous indomethacin.

PMID- 29660475
TI  - Transcriptome sequencing of active buds from Populus deltoides CL. and Populus *
      zhaiguanheibaiyang reveals phytohormones involved in branching.
AB  - Branching in woody plants affects their ecological benefits and impacts wood
      formation. To obtain genome-wide insights into the transcriptome changes and
      regulatory mechanisms associated with branching, we performed high-throughput RNA
      sequencing to characterize cDNA libraries generated from active buds of Populus
      deltoides CL. 'zhonglin2025' (BC) and Populus * zhaiguanheibaiyang (NC). NC has
      more branches than BC and rapid growth. We obtained a total of 198.2 million high
      quality clean reads from the NC and BC libraries. We detected 3543 differentially
      expressed genes (DEGs) between the NC and BC libraries; 1418 were down-regulated
      and 2125 were up-regulated. Gene ontology functional classification of the DEGs
      indicated that they included 89 genes that encoded proteins related to hormone
      biosynthesis, 364 genes related to hormone signaling transduction, and 104
      related to the auxin efflux transmembrane transporter. We validated the
      expression profiles of 16 degrees  by real-time quantitative PCR and found that
      their expression patterns were similar to those obtained from the high-throughput
      RNA sequencing data. We also measured the hormone content in young buds of BC and
      NC by high-pressure liquid chromatography. In this study, we identified global
      hormone regulatory patterns and differences in gene expression between NC and BC,
      and constructed a hormone regulatory network to explain branching in Populus
      buds. In addition, candidate genes that may be useful for molecular breeding of
      particular plant types were identified. Our results will provide a starting point
      for future investigations into the molecular mechanisms of branching in Populus.

PMID- 29660476
TI  - The first mitochondrial genome of the model echinoid Lytechinus variegatus and
      insights into Odontophoran phylogenetics.
AB  - Assembly of publically available next-generation sequence data facilitated the
      generation of three camarodont echinoid mitogenomes: two for the Green Urchin
      (Lytechinus variegatus) and one for the Red Urchin (Mesocentrotus franciscanus).
      The data generated are exploited in a phylogenomic analysis of the superfamily
      Odontophora, originally proposed for echinoids with tooth supports on the
      epiphyses of the jaw. The analysis highly supports this taxon and its current
      subdivision into three families: the Echinometridae, Toxopneustidae, and
      Strongylocentrotidae. The analysis furthermore implies that historical taxonomic
      issues between two members of the genus Strongylocentrotus (S. pallidus and S.
      droebachiensis) may have a genetic basis. The novel mitogenomes for the model
      species L. variegatus complements the draft genome available for this taxon, one
      of only three genome-enabled echinoid species. The assembly method applied
      herein, follows a divide-and-conquer approach that provides for reduced
      computational requirements and facilitates resolving assembly problems when
      processing ultra-high coverage next-generation sequence data.

PMID- 29660477
TI  - Gene selection using hybrid binary black hole algorithm and modified binary
      particle swarm optimization.
AB  - In cancer classification, gene selection is an important data preprocessing
      technique, but it is a difficult task due to the large search space. Accordingly,
      the objective of this study is to develop a hybrid meta-heuristic Binary Black
      Hole Algorithm (BBHA) and Binary Particle Swarm Optimization (BPSO) (4-2) model
      that emphasizes gene selection. In this model, the BBHA is embedded in the BPSO
      (4-2) algorithm to make the BPSO (4-2) more effective and to facilitate the
      exploration and exploitation of the BPSO (4-2) algorithm to further improve the
      performance. This model has been associated with Random Forest Recursive Feature
      Elimination (RF-RFE) pre-filtering technique. The classifiers which are evaluated
      in the proposed framework are Sparse Partial Least Squares Discriminant Analysis
      (SPLSDA); k-nearest neighbor and Naive Bayes. The performance of the proposed
      method was evaluated on two benchmark and three clinical microarrays. The
      experimental results and statistical analysis confirm the better performance of
      the BPSO (4-2)-BBHA compared with the BBHA, the BPSO (4-2) and several state-of
      the-art methods in terms of avoiding local minima, convergence rate, accuracy and
      number of selected genes. The results also show that the BPSO (4-2)-BBHA model
      can successfully identify known biologically and statistically significant genes
      from the clinical datasets.

PMID- 29660478
TI  - Cancer theranostic applications of lipid-based nanoparticles.
AB  - A variety of nanoplatforms have been developed and applied for cancer therapy,
      imaging, or the combination thereof. These nanoplatforms, combined with
      therapeutic and imaging functionalities, display great potential to enhance
      medical care. In particular, lipid-based nanoparticles (LNPs) are among the most
      studied platforms that have resulted in many encouraging advances in
      theranostics. LNPs are biodegradable and biocompatible, and their formulation can
      be tailored for various applications. Here, we provide an overview of recent
      developments of four representative LNP platforms for theranostics: stealth
      liposomes, triggered-release liposomes, porphysomes, and lipid-coated calcium
      phosphate NPs (LCPs). We discuss their potential, limitations, and potential
      applications for cancer care and highlight perspectives and future directions for
      the nanotheranostics field.

PMID- 29660479
TI  - Nanodiamond applications in skin preparations.
AB  - The biocompatibility and nontoxicity of nanodiamonds (NDs) in combination with
      their excellent physical performance have rendered them attractive candidates for
      biomedical applications. NDs have great potential in drug nanoformulations
      because of their small size compared with other carbon nanomaterials. They are
      nontoxic with excellent adsorption properties and can be formulated into skin
      care products. Even though NDs have shown encouraging potential in skin
      preparations, only a few studies have reviewed their application in topical drug
      delivery systems. Therefore, here we focus on the application of NDs in skin care
      preparations, skin cancer medication, and wound healing. We also highlight the
      development of topical drug delivery by NDs and their cytotoxicity.

PMID- 29660480
TI  - Reply to letter to the editor by C. Faggion: reproducibility and reporting
      guidelines.

PMID- 29660481
TI  - Scoping review identifies significant number of knowledge translation theories,
      models, and frameworks with limited use.
AB  - OBJECTIVES: To conduct a scoping review of knowledge translation (KT) theories,
      models, and frameworks that have been used to guide dissemination or
      implementation of evidence-based interventions targeted to prevention and/or
      management of cancer or other chronic diseases. STUDY DESIGN AND SETTING: We used
      a comprehensive multistage search process from 2000 to 2016, which included
      traditional bibliographic database searching, searching using names of theories,
      models and frameworks, and cited reference searching. Two reviewers independently
      screened the literature and abstracted the data. RESULTS: We found 596 studies
      reporting on the use of 159 KT theories, models, or frameworks. A majority (87%)
      of the identified theories, models, or frameworks were used in five or fewer
      studies, with 60% used once. The theories, models, and frameworks were most
      commonly used to inform planning/design, implementation and evaluation
      activities, and least commonly used to inform dissemination and
      sustainability/scalability activities. Twenty-six were used across the full
      implementation spectrum (from planning/design to sustainability/scalability)
      either within or across studies. All were used for at least individual-level
      behavior change, whereas 48% were used for organization-level, 33% for community
      level, and 17% for system-level change. CONCLUSION: We found a significant number
      of KT theories, models, and frameworks with a limited evidence base describing
      their use.

PMID- 29660482
TI  - Testing for reproducibility: a missing point in reporting.

PMID- 29660483
TI  - Cough and airway defence - Special issue of respiratory physiology and
      neurobiology.

PMID- 29660484
TI  - Evaluation of respiratory parameters in finswimmers regarding gender, swimming
      style and distance.
AB  - AIM: The purpose of our study was to investigate the differences in the
      finswimmers' physiological characteristics, as far as gender, the swimming style
      and the different swimming distance are concerned. METHODS: 52 finswimmers
      participated in our study (Age: 17.4 +/- 2.1yrs, BMI: 21.8 +/- 2.3, body fat:
      12.2 +/- 4.7%) and were allocated into groups [Gender: Female vs. Male, swimming
      style: Bifin vs. Surface, and swimming distance: <200 m vs. >=200 m].
      Anthropometric characteristics, handgrip, estimated strength of inspiratory
      muscles (PImax) and pulmonary function parameters (FEV1, FVC and PEF) were
      measured. The Independent T-test was used for statistical comparisons between
      groups. Multivariate analyses were performed via binary logistic regression.
      RESULTS: The results showed differences between groups in gender in PEF (p <
      0.05), PImax (p < 0.05) and handgrip (p < 0.001) in swimming style in handgrip (p
      < 0.05), FEV1 (p < 0.05) and FVC (p < 0.05) and in swimming distance (p < 0.05)
      in hours/day spent at the gym (p < 0.05) and FVC (p < 0.05). In multivariate
      analyses handgrip remained an independent predictor of style (OR: 1.154; 95%CI:
      1.022-1.303, p = .021), and hours/day spent at the gym was retained as an
      independent predictor of distance (OR: 131.607; 95%CI: 3.655-4739.441, p = .008).
      CONCLUSION: The data from the present study reveal that handgrip was associated
      with style, and hours per day spent at the gym were associated with distance.

PMID- 29660485
TI  - In silico design of ligand triggered RNA switches.
AB  - This contribution sketches a work flow to design an RNA switch that is able to
      adapt two structural conformations in a ligand-dependent way. A well
      characterized RNA aptamer, i.e., knowing its Kd and adaptive structural features,
      is an essential ingredient of the described design process. We exemplify the
      principles using the well-known theophylline aptamer throughout this work. The
      aptamer in its ligand-binding competent structure represents one structural
      conformation of the switch while an alternative fold that disrupts the binding
      competent structure forms the other conformation. To keep it simple we do not
      incorporate any regulatory mechanism to control transcription or translation. We
      elucidate a commonly used design process by explicitly dissecting and explaining
      the necessary steps in detail. We developed a novel objective function which
      specifies the mechanistics of this simple, ligand-triggered riboswitch and
      describe an extensive in silico analysis pipeline to evaluate important kinetic
      properties of the designed sequences. This protocol and the developed software
      can be easily extended or adapted to fit novel design scenarios and thus can
      serve as a template for future needs.

PMID- 29660486
TI  - Real-time imaging of specific genomic loci in eukaryotic cells using the ANCHOR
      DNA labelling system.
AB  - Spatio-temporal organization of the cell nucleus adapts to and regulates genomic
      processes. Microscopy approaches that enable direct monitoring of specific
      chromatin sites in single cells and in real time are needed to better understand
      the dynamics involved. In this chapter, we describe the principle and development
      of ANCHOR, a novel tool for DNA labelling in eukaryotic cells. Protocols for use
      of ANCHOR to visualize a single genomic locus in eukaryotic cells are presented.
      We describe an approach for live cell imaging of a DNA locus during the entire
      cell cycle in human breast cancer cells.

PMID- 29660487
TI  - Monitoring the progression of erosive tooth wear (ETW) using BEWE index in casts
      and their 3D images: A retrospective longitudinal study.
AB  - OBJECTIVE: To determine if the Basic erosive tooth wear index (BEWE index) is
      able to assess and monitor ETW changes in two consecutive cast models, and detect
      methodological differences when using the corresponding 3D image replicas.
      METHODS: A total of 480 pre-treatment and 2-year post-treatment orthodontic
      models (n = 240 cast models and n = 240 3D image replicas) from 120 adolescents
      treated between 2002 and 2013 at the Gent Dental Clinic, Belgium, were scored
      using the BEWE index. For data analysis only posterior sextants were considered,
      and inter-method differences were evaluated using Wilcoxon Signed Rank test,
      Kappa values and Mc Nemar tests (p < 0.05). Correlations between methods were
      determined using Kendall tau correlation test. RESULTS: Significant changes of
      ETW were detected between two consecutive models when BEWE index was used to
      score cast models or their 3D image replicas (p < 0.001). A strong significant
      correlation (taub: 0.74; p < 0.001) was shown between both methods However, 3D
      image-BEWE index combination showed a higher probability for detecting initial
      surface changes, and scored significantly higher than casts (p < 0.001).
      Incidence and progression of ETW using 3D images was 13.3% (n = 16) and 60.9% (n
      = 56) respectively, with two subjects developing BEWE = 3 in at least one tooth
      surface. CONCLUSIONS: BEWE index is a suitable tool for the scoring of ETW
      lesions in 3D images and cast. The combination of both digital 3D records and
      index, can be used for the monitoring of ETW in a longitudinal approach. The
      higher sensibility of BEWE index when scoring 3D images might improve the early
      diagnosis of ETW lesions. CLINICAL SIGNIFICANCE: The BEWE index combined with
      digital 3D records of oral conditions might improve the practitioner performance
      with respect to early diagnosis, monitoring and managing ETW.

PMID- 29660488
TI  - Changes in the radicular pulp-dentine complex in healthy intact teeth and in
      response to deep caries or restorations: A histological and histobacteriological
      study.
AB  - INTRODUCTION: The present study reported the histological events that occurred in
      the radicular pulp of human mature teeth in the presence of medium/deep untreated
      caries lesions, and those teeth with restorations or direct pulp capping, with
      particular emphasis on the morphology of the canal wall dentine and the
      odontoblast layer. METHODS: Sixty-two teeth with medium/deep caries lesions,
      extensive restorations or after application of a direct pulp capping procedure
      were obtained from 57 subjects. Fourteen intact mature teeth served as controls.
      Stained serial sections were examined for the pulp conditions of the coronal
      pulp. The teeth were classified as those with pulpal inflammation, or those with
      healed pulps. Histological changes that occurred in the roots at the pulp-dentine
      junction were investigated in detail. RESULTS: All teeth (100%) in the
      experimental group showed pathologic changes in the radicular pulp, with varying
      amounts of tertiary dentine on the canal walls and absence of odontoblasts. These
      changes were identified from different portions of the canal wall surface. Non
      adherent calcifications in the pulp tissue were observed in more than half of the
      specimens. Changes that deviate from classically-perceived histological
      relationships of the pulp-dentine complex were also observed in the radicular
      pulps of 33.7% of the control teeth. CONCLUSION: When challenged by bacteria and
      bacterial by-products invading dentinal tubules, odontoblasts in the radicular
      pulp may undergo cell death, possibly by apoptosis. This phenomenon may be caused
      by progressive root-ward diffusion of bacterial by-products, cytokines or
      reactive oxygen species through the pulp connective tissue. CLINICAL
      SIGNIFICANCE: Although the vitality of the dental pulp in teeth with deep
      dentinal caries may be maintained with direct pulp capping or pulpotomy, the
      repair tissue that is formed resembles mineralised fibrous connective tissues
      more than true tubular dentine.

PMID- 29660490
TI  - Subjectivity about Turnover Intention among Male Nurses in South Korea: A Q
      Methodological Study.
AB  - PURPOSE: Around the world, male nurses face a variety of difficulties within
      clinical settings; accordingly, a large number of male nurses consider changing
      their occupation. In particular, male nurses in a number of Asian countries with
      a Confucian heritage experience difficulties. Thus, the purpose of this study was
      to explore individual differences in turnover intention among male nurses in one
      such country, South Korea, and on that basis to suggest concrete strategies for
      reducing turnover among male nurses in Confucian cultures. METHODS: Q
      methodology, which is used to analyze human subjectivity, was applied. Q
      statements were derived from 207 candidate statements gathered from various
      documents and interviews; 40 statements were finalized. A purposive sample of 41
      male nurses were selected as likely to have diverse opinions on turnover
      intention of male nurses. The collected data were analyzed using PQMethod
      software. RESULTS: Four distinct types of subjectivity about turnover intention
      among male nurses were identified: (1) "Pursuing occupational values," (2)
      "Dissatisfaction with treatment," (3) "Seeking a relaxed and stable life," and
      (4) "Conflict related to organizational culture." CONCLUSIONS: This study
      suggests various ways of reducing turnover and increasing retention among male
      nurses based on the four identified perspectives, especially in Confucian
      heritage regions.

PMID- 29660489
TI  - Prevalence of mucosal and cutaneous human papillomavirus in Moroccan breast
      cancer.
AB  - BACKGROUND: Due to recent technical improvements and some encouraging new
      results, there has been a resurgence of interest in the possibility that a
      substantial proportion of breast cancers (BCs) may be caused by viral infections,
      including Human papillomavirus (HPV). The aim of this study was to determine the
      prevalence of mucosal and cutaneous HPV in tumours from Moroccan BC patients.
      MATERIALS AND METHODS: Frozen tumours from 76 BC cases and 12 controls were
      evaluated for the presence of 62 HPV-types using highly sensitive assays that
      combine multiplex polymerase chain reaction and bead-based Luminex technology.
      RESULTS: HPV DNA was found in 25.0% of BC tumours and only 8.3% of controls. Beta
      and gamma HPV types were found in 10.5% and 6.6% of BC tumours, respectively.
      High-risk mucosal types HPV16 and 18 were not detected in the subjects, but other
      probable/possible high-risk or high-risk -HPV types (HPV51, 52, 58, 59, and 66)
      were found in 5.3% of BC tumours. Statistical analysis showed no significant
      difference between, controls, BC cases and the inflammatory status (p > 0.05).
      CONCLUSION: HPV DNA was found 3 times as frequently in the BC tumours as in the
      controls. However, this difference requires confirmation in a larger sample.

PMID- 29660491
TI  - C-terminal oligomerization of podocin mediates interallelic interactions.
AB  - Interallelic interactions of membrane proteins are not taken into account while
      evaluating the pathogenicity of sequence variants in autosomal recessive
      disorders. Podocin, a membrane-anchored component of the slit diaphragm, is
      encoded by NPHS2, the major gene mutated in hereditary podocytopathies. We
      formerly showed that its R229Q variant is only pathogenic when trans-associated
      to specific 3' mutations and suggested the causal role of an abnormal C-terminal
      dimerization. Here we show by FRET analysis and size exclusion chromatography
      that podocin oligomerization occurs exclusively through the C-terminal tail
      (residues 283-382): principally through the first C-terminal helical region (H1,
      283-313), which forms a coiled coil as shown by circular dichroism spectroscopy,
      and through the 332-348 region. We show the principal role of the oligomerization
      sites in mediating interallelic interactions: while the monomer-forming
      R286Tfs*17 podocin remains membranous irrespective of the coexpressed podocin
      variant identity, podocin variants with an intact H1 significantly influence each
      other's localization (r2 = 0.68, P = 9.2 * 10-32). The dominant negative effect
      resulting in intracellular retention of the pathogenic F344Lfs*4-R229Q
      heterooligomer occurs in parallel with a reduction in the FRET efficiency,
      suggesting the causal role of a conformational rearrangement. On the other hand,
      oligomerization can also promote the membrane localization: it can prevent the
      endocytosis of F344Lfs*4 or F344* podocin mutants induced by C-terminal
      truncation. In conclusion, C-terminal oligomerization of podocin can mediate both
      a dominant negative effect and interallelic complementation. Interallelic
      interactions of NPHS2 are not restricted to the R229Q variant and have to be
      considered in compound heterozygous individuals.

PMID- 29660492
TI  - Characterization of multiple enolase genes from Trichomonas vaginalis. Potential
      novel targets for drug and vaccine design.
AB  - Trichomonas vaginalis is the protist parasite that causes the most common, non
      viral sexually transmitted infection called trichomonosis. Enolase is a
      moonlighting protein that apart from its canonical function as a glycolytic
      enzyme, serves as a plasminogen receptor on the cell surface of T. vaginalis and,
      in consequence, it has been stablished as a virulence factor in this parasite. In
      the Trichomonas vaginalis sequence database there are nine genes annotated as
      enolase. In this work, we analyzed these genes as well as their products. We
      found that seven out of nine genes might indeed perform enolase activity, whereas
      two genes might have been equivocally identified, or they might be pseudogenes.
      Furthermore, a combination of qRT-PCR and proteomic approaches was used to
      assess, for the first time, the expression of these genes in the highly virulent
      mexican isolate of T. vaginalis CNCD-147 at different iron concentrations. We
      could find peptides corresponding to enolases encoded by genes TVAG_464170,
      TVAG_043500 and TVAG_329460. Moreover, we identified two distinctive
      characteristics within enolases from Trichomonas vaginalis. One of them
      corresponds to three key substitutions within one of the loops of the active
      site, compared to host enolase. The other, is a unique N-terminal motif, composed
      of 15 to 18 residues, on all the potentially active enolases, whose function
      still has to be stablished. Both differential features merit further studies as
      potential drug and vaccine targets as well as diagnosis markers. These findings
      offer new possibilities to fight trichomonosis.

PMID- 29660493
TI  - Effect of absolute monocyte count post-transplant on the outcome of patients with
      acute myeloid leukemia undergoing myeloablative allogeneic hematopoietic stem
      cell transplant with busulfan and cyclophosphamide conditioning.
AB  - Peripheral monocytes have recently been evaluated as a prognostic factor in
      different types of hematological malignancies. This study assessed the prognostic
      value of absolute monocyte count (AMC) post-transplant on the clinical outcomes
      of 59 patients with acute myeloid leukemia (AML) who had undergone myeloablative
      conditioning (MAC) allogeneic hematopoietic stem cell transplant (allo-HSCT) with
      busulfan and cyclophosphamide (Bu/Cy). Kaplan-Meier analysis showed that patients
      with a high AMC (>= 0.57 * 109/L) on post-transplant day (PTD) 15 had a
      significantly worse overall survival (OS) compared to patients with a low AMC (<
      0.57 * 109/L) on PTD 15 (P = .0049). Univariate Cox proportional hazard analyses
      revealed that only high AMC on PTD 15 was a poor prognostic factor for OS (P =
      .008) and post-relapse survival (P = .030). We conclude that AMC >= 0.57 * 109/L
      on PTD 15 is associated with more deaths in patients with AML who have undergone
      MAC allo-HSCT with Bu/Cy.

PMID- 29660494
TI  - Accurate filtering of privacy-sensitive information in raw genomic data.
AB  - Sequencing thousands of human genomes has enabled breakthroughs in many areas,
      among them precision medicine, the study of rare diseases, and forensics.
      However, mass collection of such sensitive data entails enormous risks if not
      protected to the highest standards. In this article, we follow the position and
      argue that post-alignment privacy is not enough and that data should be
      automatically protected as early as possible in the genomics workflow, ideally
      immediately after the data is produced. We show that a previous approach for
      filtering short reads cannot extend to long reads and present a novel filtering
      approach that classifies raw genomic data (i.e., whose location and content is
      not yet determined) into privacy-sensitive (i.e., more affected by a successful
      privacy attack) and non-privacy-sensitive information. Such a classification
      allows the fine-grained and automated adjustment of protective measures to
      mitigate the possible consequences of exposure, in particular when relying on
      public clouds. We present the first filter that can be indistinctly applied to
      reads of any length, i.e., making it usable with any recent or future sequencing
      technologies. The filter is accurate, in the sense that it detects all known
      sensitive nucleotides except those located in highly variable regions (less than
      10 nucleotides remain undetected per genome instead of 100,000 in previous
      works). It has far less false positives than previously known methods (10%
      instead of 60%) and can detect sensitive nucleotides despite sequencing errors
      (86% detected instead of 56% with 2% of mutations). Finally, practical
      experiments demonstrate high performance, both in terms of throughput and memory
      consumption.

PMID- 29660495
TI  - How program evaluators use and learn to use rubrics to make evaluative reasoning
      explicit.
AB  - A rubric is a tool that can support evaluators in a core function of their
      practice-the process of combining evidence with values to determine merit, worth,
      or significance-however, little guidance specific to evaluation exists. This
      study examined, through semi-structured interviews, how a rare group of nine
      rubric-using seasoned evaluators from across the globe use and learned to use
      rubrics in their program evaluation practice. Key findings revealed rubrics were
      a critical component to the practice of these evaluators to make determinations,
      but also as frameworks to sharpen an evaluation's focus. Additionally, findings
      support the notion that there is a paucity of formal channels for learning about
      rubrics and indicate these early adopters are instead, honing their skills
      through informal channels such as trial and error and by tapping into a community
      of practice. Future directions for training and research should include expanding
      understanding, application, and acceptance of use.

PMID- 29660497
TI  - Proteomics in infectious diseases.

PMID- 29660496
TI  - Quantitative targeted proteomic analysis of potential markers of tyrosine kinase
      inhibitor (TKI) sensitivity in EGFR mutated lung adenocarcinoma.
AB  - Lung cancer causes the highest mortality among all cancers. Patients harboring
      kinase domain mutations in the epidermal growth factor receptor (EGFR) respond to
      EGFR tyrosine kinase inhibitors (TKIs), however, acquired resistance always
      develops. Moreover, 30-40% of patients with EGFR mutations exhibit primary
      resistance. Hence, there is an unmet need for additional biomarkers of TKI
      sensitivity that complement EGFR mutation testing and predict treatment response.
      We previously identified phosphopeptides whose phosphorylation is inhibited upon
      treatment with EGFR TKIs, erlotinib and afatinib in TKI sensitive cells, but not
      in resistant cells. These phosphosites are potential biomarkers of TKI
      sensitivity. Here, we sought to develop modified immuno-multiple reaction
      monitoring (immuno-MRM)-based quantitation assays for select phosphosites
      including EGFR-pY1197, pY1172, pY998, AHNAK-pY160, pY715, DAPP1-pY139, CAV1-pY14,
      INPPL1-pY1135, NEDD9-pY164, NF1-pY2579, and STAT5A-pY694. These sites were
      significantly hypophosphorylated by erlotinib and a 3rd generation EGFR TKI,
      osimertinib, in TKI-sensitive H3255 cells, which harbor the TKI-sensitizing
      EGFRL858R mutation. However, in H1975 cells, which harbor the TKI-resistant
      EGFRL858R/T790M mutant, osimertinib, but not erlotinib, could significantly
      inhibit phosphorylation of EGFR-pY-1197, STAT5A-pY694 and CAV1-pY14, suggesting
      these sites also predict response in TKI-resistant cells. We could further
      validate EGFR-pY-1197 as a biomarker of TKI sensitivity by developing a
      calibration curve-based modified immuno-MRM assay. SIGNIFICANCE: In this report,
      we have shown the development and optimization of MRM assays coupled with global
      phosphotyrosine enrichment (modified immuno-MRM) for a list of 11 phosphotyrosine
      peptides. Our optimized assays identified the targets reproducibly in biological
      samples with good selectivity. We also developed and characterized quantitation
      methods to determine endogenous abundance of these targets and correlated the
      results of the relative quantification with amounts estimated from the
      calibration curves. This approach represents a way to validate and verify
      biomarker candidates discovered from large-scale global phospho-proteomics
      analysis. The application of these modified immuno-MRM assays in lung
      adenocarcinoma cells provides proof-of concept for the feasibility of clinical
      applications. These assays may be used in prospective clinical studies of EGFR
      TKI treatment of EGFR mutant lung cancer to correlate treatment response and
      other clinical endpoints.

PMID- 29660498
TI  - Morphinome Database - The database of proteins altered by morphine administration
      - An update.
AB  - Morphine is considered a gold standard in pain treatment. Nevertheless, its use
      could be associated with severe side effects, including drug addiction. Thus, it
      is very important to understand the molecular mechanism of morphine action in
      order to develop new methods of pain therapy, or at least to attenuate the side
      effects of opioids usage. Proteomics allows for the indication of proteins
      involved in certain biological processes, but the number of items identified in a
      single study is usually overwhelming. Thus, researchers face the difficult
      problem of choosing the proteins which are really important for the investigated
      processes and worth further studies. Therefore, based on the 29 published
      articles, we created a database of proteins regulated by morphine administration 
      The Morphinome Database (addiction-proteomics.org). This web tool allows for
      indicating proteins that were identified during different proteomics studies.
      Moreover, the collection and organization of such a vast amount of data allows us
      to find the same proteins that were identified in various studies and to create
      their ranking, based on the frequency of their identification. STRING and KEGG
      databases indicated metabolic pathways which those molecules are involved in.
      This means that those molecular pathways seem to be strongly affected by morphine
      administration and could be important targets for further investigations.
      SIGNIFICANCE: The data about proteins identified by different proteomics studies
      of molecular changes caused by morphine administration (29 published articles)
      were gathered in the Morphinome Database. Unification of those data allowed for
      the identification of proteins that were indicated several times by distinct
      proteomics studies, which means that they seem to be very well verified and
      important for the entire process. Those proteins might be now considered
      promising aims for more detailed studies of their role in the molecular mechanism
      of morphine action.

PMID- 29660499
TI  - Modulating membrane fluidity corrects Batten disease phenotypes in vitro and in
      vivo.
AB  - The neuronal ceroid lipofuscinoses are a class of inherited neurodegenerative
      diseases characterized by the accumulation of autofluorescent storage material.
      The most common neuronal ceroid lipofuscinosis has juvenile onset with rapid
      onset blindness and progressive degeneration of cognitive processes. The juvenile
      form is caused by mutations in the CLN3 gene, which encodes the protein CLN3.
      While mouse models of Cln3 deficiency show mild disease phenotypes, it is
      apparent from patient tissue- and cell-based studies that its loss impacts many
      cellular processes. Using Cln3 deficient mice, we previously described defects in
      mouse brain endothelial cells and blood-brain barrier (BBB) permeability. Here we
      expand on this to other components of the BBB and show that Cln3 deficient mice
      have increased astrocyte endfeet area. Interestingly, this phenotype is corrected
      by treatment with a commonly used GAP junction inhibitor, carbenoxolone (CBX). In
      addition to its action on GAP junctions, CBX has also been proposed to alter
      lipid microdomains. In this work, we show that CBX modifies lipid microdomains
      and corrects membrane fluidity alterations in Cln3 deficient endothelial cells,
      which in turn improves defects in endocytosis, caveolin-1 distribution at the
      plasma membrane, and Cdc42 activity. In further work using the NIH Library of
      Integrated Network-based Cellular Signatures (LINCS), we discovered other small
      molecules whose impact was similar to CBX in that they improved Cln3-deficient
      cell phenotypes. Moreover, Cln3 deficient mice treated orally with CBX exhibited
      recovery of impaired BBB responses and reduced autofluorescence. CBX and the
      compounds identified by LINCS, many of which have been used in humans or approved
      for other indications, may find therapeutic benefit in children suffering from
      CLN3 deficiency through mechanisms independent of their original intended use.

PMID- 29660500
TI  - Occurrence and seasonal variation of equine estrogens, equilin and equilenin, in
      the river water of Japan: Implication with endocrine-disrupting potentials to
      Japanese medaka (Oryzias latipes).
AB  - In this study, we determined the concentration of equine estrogens, such as
      equilin (Eq) and equilenin (Eqn), in the river water collected from nine research
      stations in Hokkaido, Japan. The LC-MS/MS analysis revealed that Eq
      concentrations were 2.7 +/- 6.7, 0.22 +/- 0.12, and 1.2 +/- 0.64 ng/L in Sep
      2015, Feb 2016, and Jul 2016, respectively. Eqn had concentration levels similar
      to those of Eq. Comparison of the concentrations at nine research stations showed
      that seasonal variation was observed in the detected Eq and Eqn concentration
      levels. This study was the first to show the occurrences and seasonal variation
      of Eq and Eqn in the river water of Japan. We further investigated the
      reproductive and transgenerational effects of Eq in Japanese medaka (Oryzias
      latipes) exposed to 10, 100, and 1000 ng/L for 21 days and assessed the
      transcriptional profiles of the estrogen-responsive genes in the livers of both
      sexes. The reproduction assay demonstrated that 1000 ng/L of Eq adversely
      affected the reproduction (i.e. fecundity) in the F0 generation and that the
      hatching of F1 generation fertilized eggs was reduced in the 100 and 1000 ng/L
      treatment groups. Our qRT-PCR assay revealed that the mRNA expression levels of
      hepatic vitellogenin 1 and 2, choriogenin L and H, and estrogen receptor alpha
      were significantly up-regulated in males exposed to 100 and/or 1000 ng/L of Eq.
      In contrast, the transcriptional levels of several genes, such as pregnane X
      receptor and cytochrome P450 3A, were down-regulated in the livers of males after
      the 21-d exposure. These results suggest that Eq has endocrine-disrupting
      potential such as reproductive and transgenerational effects by the modulation of
      hepatic estrogen-responsive genes expression on medaka.

PMID- 29660501
TI  - Characteristics of CH4 and CO2 emissions and influence of water and salinity in
      the Yellow River delta wetland, China.
AB  - Due to the severe degradation and environmental pollution of coastal wetlands by
      human activities, they have gradually become an important source of greenhouse
      gases (GHGs) emissions, so exploring the characteristics of their emission is
      important to reduce greenhouse gas emissions from coastal wetlands. In this
      study, the dynamics of methane (CH4) and carbon dioxide (CO2) emissions were
      investigated in five kinds of typical tidal flats from the Yellow River delta
      wetland during the years 2011-2013, and the influences of water level and
      salinity on their emissions were explored in laboratory experiments. The mean
      fluxes of CO2 and CH4 were -20.98 to 68.12 mg m-2 h-1 and -0.12 to 0.44 mg m-2 h
      1 across all seasons in the five kinds of representative tidal flats. The highest
      and lowest mean fluxes of CO2 were mainly observed during summer and winter,
      respectively, whereas the seasons with the highest and lowest mean fluxes of CH4
      varied according to the type of tidal flat. The results showed that the summer
      season and the mud flat environment had the largest contributions to greenhouse
      gas emissions. In laboratory experiments, the largest sequestration fluxes of CO2
      and CH4 were observed with +4/+2 cm and -4 cm water levels, respectively,
      indicating that a moderately high water level was beneficial for CO2
      sequestration but led to the increase of CH4 emission. In the study of salinity,
      we found that the largest sequestration fluxes of CO2 and CH4 were both detected
      at 24 g L-1 salinity, indicating that high salinity level was advantageous for
      CO2 and CH4 sequestration in the five simulation devices. Furthermore, a carbon
      cycle pathway of coastal wetlands was proposed, which could have a vital
      significance for research into the global carbon cycle. We can reduce GHG
      emissions by protecting the coastal wetlands and lessening human activities.

PMID- 29660502
TI  - The place of fibrinogen concentrates in the management of perioperative bleeding:
      A position paper from the Francophone Working Group on Perioperative Haemostasis
      (GIHP).
AB  - The consumption of fibrinogen concentrates has been increasing steadily for
      several years in surgery, trauma and obstetrics. However, data from the
      literature are conflicting. The French Working Group on Perioperative Haemostasis
      (GIHP) proposes a position paper based on a narrative review of the literature,
      and addresses the following questions: What is the exact role of fibrinogen in
      haemostasis? Which rational support for the use of perioperative fibrinogen?
      Which thrombotic risk? What are the most recent professional recommendations on
      the use of fibrinogen concentrates? Then, evidence-based recommendations are
      proposed: 1) it is suggested not to administer prophylactic FC to prevent
      haemorrhage; 2) it is suggested not to use FC alone. Haemostatic treatment must
      be comprehensive, include other haemostatic treatments and must be limited in
      cases of severe active haemorrhage; 3) the GIHP suggests urgent measurement of
      fibrinogen plasma concentration in a biology laboratory or functional fibrinogen
      by viscoelastic methods. The choice between the two methods must be guided by the
      time to receive the results from a certified organisation with, in particular,
      authorisation to perform delocalised biologic examinations; 4) it is suggested
      not to administer FC when the fibrinogen concentration is superior to 1.5g/L or
      when there is a functional fibrinogen deficit (with the possible exception in
      obstetrics where the threshold could be 2.0g/L); 5) if FC are administered, an
      initial dose of 25-50mg/kg is proposed.

PMID- 29660503
TI  - High circulatory leptin mediated NOX-2-peroxynitrite-miR21 axis activate
      mesangial cells and promotes renal inflammatory pathology in nonalcoholic fatty
      liver disease.
AB  - High circulatory insulin and leptin followed by underlying inflammation are often
      ascribed to the ectopic manifestations in non-alcoholic fatty liver disease
      (NAFLD) but the exact molecular pathways remain unclear. We have shown previously
      that CYP2E1-mediated oxidative stress and circulating leptin in NAFLD is
      associated with renal disease severity. Extending the studies, we hypothesized
      that high circulatory leptin in NAFLD causes renal mesangial cell activation and
      tubular inflammation via a NOX2 dependent pathway that upregulates
      proinflammatory miR21. High-fat diet (60% kcal) was used to induce fatty liver
      phenotype with parallel insulin and leptin resistance. The kidneys were probed
      for mesangial cell activation and tubular inflammation that showed accelerated
      NASH phenotype and oxidative stress in the liver. Results showed that NAFLD
      kidneys had significant increases in alpha-SMA, a marker of mesangial cell
      activation, miR21 levels, tyrosine nitration and renal inflammation while they
      were significantly decreased in leptin and p47 phox knockout mice. Micro RNA21
      knockout mice showed decreased tubular immunotoxicity and proinflammatory
      mediator release. Mechanistically, use of NOX2 siRNA or apocynin,phenyl boronic
      acid (FBA), DMPO or miR21 antagomir inhibited leptin primed-miR21-mediated
      mesangial cell activation in vitro suggesting a direct role of leptin-mediated
      NOX-2 in miR21-mediated mesangial cell activation. Finally, JAK-STAT inhibitor
      completely abrogated the mesangial cell activation in leptin-primed cells
      suggesting that leptin signaling in the mesangial cells depended on the JAK-STAT
      pathway. Taken together the study reports a novel mechanistic pathway of leptin
      mediated renal inflammation that is dependent on NOX-2-miR21 axis in ectopic
      manifestations underlying NAFLD-induced co-morbidities.

PMID- 29660504
TI  - IDH2 deficiency accelerates skin pigmentation in mice via enhancing
      melanogenesis.
AB  - Melanogenesis is a complex biosynthetic pathway regulated by multiple agents,
      which are involved in the production, transport, and release of melanin. Melanin
      has diverse roles, including determination of visible skin color and
      photoprotection. Studies indicate that melanin synthesis is tightly linked to the
      interaction between melanocytes and keratinocytes. alpha-melanocyte-stimulating
      hormone (alpha-MSH) is known as a trigger that enhances melanin biosynthesis in
      melanocytes through paracrine effects. Accumulated reactive oxygen species (ROS)
      in skin affects both keratinocytes and melanocytes by causing DNA damage, which
      eventually leads to the stimulation of alpha-MSH production. Mitochondria are one
      of the main sources of ROS in the skin and play a central role in modulating
      redox-dependent cellular processes such as metabolism and apoptosis. Therefore,
      mitochondrial dysfunction may serve as a key for the pathogenesis of skin
      melanogenesis. Mitochondrial NADP+-dependent isocitrate dehydrogenase (IDH2) is a
      key enzyme that regulates mitochondrial redox balance and reduces oxidative
      stress-induced cell injury through the generation of NADPH. Downregulation of
      IDH2 expression resulted in an increase in oxidative DNA damage in mice skin
      through ROS-dependent ATM-mediated p53 signaling. IDH2 deficiency also promoted
      pigmentation on the dorsal skin of mice, as evident from the elevated levels of
      melanin synthesis markers. Furthermore, pretreatment with mitochondria-targeted
      antioxidant mito-TEMPO alleviated oxidative DNA damage and melanogenesis induced
      by IDH2 deficiency both in vitro and in vivo. Together, our findings highlight
      the role of IDH2 in skin melanogenesis in association with mitochondrial ROS and
      suggest unique therapeutic strategies for the prevention of skin pigmentation.

PMID- 29660506
TI  - Correlates of stigma in adults with epilepsy: A systematic review of quantitative
      studies.
AB  - OBJECTIVES: The aim of this review was to identify quantitative correlates,
      predictors, and outcomes of stigma in adults with epilepsy living in Western
      countries. METHODS: To identify relevant literature, four academic databases
      (PsycINFO, CINAHL, PubMed, and Scopus) were systematically searched using key
      terms related to stigma and epilepsy. RESULTS: Thirty-three research papers
      reporting findings from 25 quantitative studies of correlates of stigma in
      epilepsy were identified. The findings suggest that stigma can be predicted by
      demographic, illness-related, and psychosocial factors, although associations
      were found to be highly culturally specific. Outcomes of stigma in people with
      epilepsy were replicated more consistently across cultures, and its impact was
      significant. Detrimental effects included both worse physical health, including
      less effective management of the condition, and reduced psychological well-being,
      including difficulties such as depression and anxiety. IMPLICATIONS: Educational
      initiatives and therapeutic interventions that aim to address stigma in people
      with epilepsy are recommended; however, these need to be culturally informed to
      ensure that they are valid and effective.

PMID- 29660505
TI  - GCN2 deficiency ameliorates doxorubicin-induced cardiotoxicity by decreasing
      cardiomyocyte apoptosis and myocardial oxidative stress.
AB  - The clinical use of doxorubicin for cancer therapy is limited by its
      cardiotoxicity, which involves cardiomyocyte apoptosis and oxidative stress.
      Previously, we showed that general control nonderepressible 2 (GCN2), an
      eukaryotic initiation factor 2alpha (eIF2alpha) kinase, impairs the ventricular
      adaptation to chronic pressure overload by affecting cardiomyocyte apoptosis.
      However, the impact of GCN2 on Dox-induced cardiotoxicity has not been
      investigated. In the present study, we treated wild type (WT) and Gcn2-/- mice
      with four intraperitoneal injections (5 mg/kg/week) to induce cardiomyopathy.
      After Dox treatment, Gcn2-/- mice developed less contractile dysfunction,
      myocardial fibrosis, apoptosis, and oxidative stress compared with WT mice. In
      the hearts of the Dox-treated mice, GCN2 deficiency attenuated eIF2alpha
      phosphorylation and induction of its downstream targets, activating transcription
      factor 4 (ATF4) and C/EBP homologous protein (CHOP), and preserved the expression
      of anti-apoptotic factor Bcl-2 and mitochondrial uncoupling protein-2(UCP2).
      Furthermore, we found that GCN2 knockdown attenuated, whereas GCN2 overexpression
      exacerbated, Dox-induced cell death, oxidative stress and reduction of Bcl-2 and
      UCP2 expression through the eIF2alpha-CHOP-dependent pathway in H9C2 cells.
      Collectively, our data provide solid evidence that GCN2 has a marked effect on
      Dox induced myocardial apoptosis and oxidative stress. Our findings suggest that
      strategies to inhibit GCN2 activity in cardiomyocyte may provide a novel approach
      to attenuate Dox-related cardiotoxicity.

PMID- 29660507
TI  - Does semiology of status epilepticus have an impact on treatment response and
      outcome?
AB  - OBJECTIVE: This study investigated whether there is an association between
      semiology of status epilepticus (SE) and response to treatment and outcome.
      METHOD: Two hundred ninety-eight consecutive adult patients (160 females, 138
      males) with SE at the University of Munich Hospital were prospectively enrolled.
      Mean age was 63.2+/-17.5 (18-97) years. Patient demographics, SE semiology and
      electroencephalography (EEG) findings, etiology, duration of SE, treatment, and
      outcome measures were investigated. Status epilepticus semiology was classified
      according to a semiological status classification. Patient's short-term outcome
      was determined by Glasgow Outcome Scale (GOS). RESULTS: The most frequent SE type
      was nonconvulsive SE (NCSE) (39.2%), mostly associated with cerebrovascular
      etiology (46.6%). A potentially fatal etiology was found in 34.8% of the
      patients. More than half (60.7%) of the patients had poor short-term outcome
      (GOS<=3) with an overall mortality of 12.4%. SE was refractory to treatment in
      21.5% of the patients. Older age, potentially fatal etiology, systemic
      infections, NCSE in coma, refractory SE, treatment with anesthetics, long SE
      duration (>24h), low Glasgow Coma Scale (GCS) (<=8) at onset, and high Status
      Epilepticus Severity Score (STESS-3) (>=3) were associated with poor short-term
      outcome and death (p<0.05). Potentially fatal etiology and low GCS were the
      strongest predictors of poor outcome (Exp [b]: 4.74 and 4.10 respectively,
      p<0.05). CONCLUSION: Status epilepticus semiology has no independent association
      with outcome, but potentially fatal etiology and low GCS were strong predictive
      factors for poor short-term outcome of SE.

PMID- 29660508
TI  - Estrone-modified pH-sensitive glycol chitosan nanoparticles for drug delivery in
      breast cancer.
AB  - : Estrone-modified glycol chitosan nanoparticles (GCNP-ES) based on the
      mechanisms of ES-mediated endocytosis and intracellular pH-responsive drug
      release were developed for the treatment of breast cancer. GCNP-ES were prepared
      by grafting copolymerization of glycol chitosan with 2-(diisopropylamino)ethyl
      methacrylate to generate GCNP prior to ES conjugation. The particle size, zeta
      potential, and paclitaxel (PTX) encapsulation efficiency of GCNP-ES were
      characterized. In particular, GCNP-ES exhibited pH-responsive dissociation
      properties while maintaining stability under long-term storage and
      lyophilization. The drug release of PTX-loaded GCNP-ES (PTX/GNCP-ES) was modestly
      prolonged with considerable pH sensitivity. GCNP-ES promoted internalization in
      breast cancer MCF-7 cells by approximately 5-fold as compared to GCNP, and the
      internalized GCNP-ES was mainly localized in the endosomes of MCF-7 cells.
      PTX/GNCP-ES exhibited higher cytotoxicity and cell apoptosis ratio than GCNP. In
      mice with MCF-7 breast cancer xenograft, PTX/GCNP-ES showed higher accumulation
      at the tumor site, which resulted in a higher tumor inhibition ratio (81.4%) than
      that achieved by PTX/GCNP (69.4%) and PTX solution (48.8%). Furthermore, no
      histological and hematological toxicity was detected in in vivo studies of
      PTX/GCNP-ES. Overall, these results suggested the potential applicability of GCNP
      ES as a drug delivery system for breast cancer therapy. STATEMENT OF
      SIGNIFICANCE: Most breast cancers are hormone dependent. Herein, we developed a
      estrone-modified glycol chitosan nanoparticles (GCNP-ES) as a drug delivery
      system to overcome the drawbacks of chemotherpeutic drugs, including poor water
      solubility and lack of specifity. GCNP-ES could provide efficient drug delivery
      in breast cancer cells. The study demonstrated that GCNP-ES could dissociate
      under mildly acidic conditions, leading to the timely payload release of the drug
      in target tumor cells following internalization. The conjugated estrone of the
      nanoparticles could significantly increase drug accumulation in the tumor site
      and result in enhanced therapeutic effect. Thus, the potential applicability of
      GCNP-ES was suggested.

PMID- 29660509
TI  - Glycosylation-enhanced biocompatibility of the supramolecular hydrogel of an anti
      inflammatory drug for topical suppression of inflammation.
AB  - : Intravitreal/periocular injection of triamcinolone acetonide (TA) suspension is
      a common uveitis treatment, but it displays a high risk for serious side effects
      (e.g., high intraocular pressure, retinal toxicity). We report here an
      intravitreally injectable thermosensitive glycosylated TA (TA-SA-Glu) hydrogel,
      formed by covalently conjugating glucosamine (Glu) with succinate TA (TA-SA), for
      treating uveitis. The TA-SA-Glu hydrogelator forms a supramolecular hydrogel
      spontaneously in aqueous solution with a minimal gelation concentration of 0.25
      wt%. Structural analysis revealed that hydrogen bonds assisted by hydrophobic
      interaction resulted in self-assembled nanofibers. Rheology analysis demonstrated
      that this TA-SA-Glu hydrogel exhibited a typical thixotropic property. Sustained
      release of both TA-SA-Glu and TA from the hydrogel occurred throughout the 3-day
      in vitro release study. The obtained TA-SA-Glu hardly caused cytotoxicity against
      ARPE-19 and RAW264.7 cells after 24 h of incubation at drug concentration up to
      600 MUM. In particular, TA-SA-Glu exhibited a comparable anti-inflammatory
      efficacy to TA in terms of inhibiting the production of nitric oxide, tumor
      necrosis factor-alpha, and interleukin-6 in activated RAW264.7 macrophages.
      Following a single intravitreal injection, 69 nmol TA-SA-Glu hydrogel caused
      minimal apparent retinal toxicity, whereas the TA suspension displayed
      significant effects in terms of localized retinal toxicity. A single intravitreal
      injection of TA-SA-Glu hydrogel was more effective in controlling inflammatory
      response than that of the TA suspension treatment, particularly in down
      regulating the pro-inflammatory Th1 and Th17 effector responses for treating
      experimental autoimmune uveitis. This study strongly indicates that
      supramolecular TA-SA-Glu hydrogels may represent a new option for posterior
      uveitis management. STATEMENT OF SIGNIFICANCE: Intravitreal/periocular injection
      of triamcinolone acetonide (TA) suspension is a common uveitis treatment, but
      suffers a high risk for serious side effects (e.g., high intraocular pressure,
      retinal toxicity). We generated an injectable glycosylated triamcinolone
      acetonide hydrogelator (TA-SA-Glu) hydrogel for treating uveitis. Following a
      single intravitreal injection, the proposed TA-SA-Glu hydrogel hardly caused
      apparent retinal toxicity at a dosage of 69 nmol per eye. Furthermore, TA-SA-Glu
      hydrogel was more effective in controlling non-infectious uveitis over than a TA
      suspension, particularly in terms of down-regulating the pro-inflammatory Th1 and
      Th17 effector responses for treating experimental autoimmune uveitis (EAU). This
      study strongly indicates that TA-SA-Glu supramolecular hydrogels may represent a
      new option for the management of various intraocular inflammations.

PMID- 29660510
TI  - The in vivo anti-fibrotic function of calcium sensitive receptor (CaSR)
      modulating poly(p-dioxanone-co-l-phenylalanine) prodrug.
AB  - : In present study, the apoptosis induction and proliferation suppression effects
      of l-phenylalanine (l-Phe) on fibroblasts were confirmed. The action sites of l
      Phe on fibroblasts suppression were deduced to be calcium sensitive receptor
      (CaSR) which could cause the release of endoplasmic reticulum (ER) Ca2+ stores;
      disruption of intracellular Ca2+ homeostasis triggers cell apoptosis via the ER
      or mitochondrial pathways. The down-regulation of CaSR were observed after the
      application of l-Phe, and the results those l-Phe triggered the increasing of
      intracellular Ca2+ concentration and calcineurin expression, and then the
      apoptosis and increasing G1 fraction of fibroblasts have verified our deduction.
      Hence, l-Phe could be seen as a kind of anti-fibrotic drugs for the crucial
      participation of fibroblast in the occurrence of fibrosis. And then, poly(p
      dioxanone-co-l-phenylalanine) (PDPA) which could prolong the in-vivo anti
      fibrotic effect of l-Phe for the sustained release of l-Phe during its
      degradation could be treated as anti-fibrotic polymer prodrugs. Based on the
      above, the in vivo anti-fibrotic function of PDPA was evaluated in rabbit ear
      scarring, rat peritoneum lipopolysaccharide, and rat sidewall defect/cecum
      abrasion models. PDPA reduced skin scarring and suppressed peritoneal fibrosis
      and post operation adhesion as well as secretion of transforming growth factor
      beta1 in injured tissue. These results indicate that PDPA is an effective agent
      for preventing fibrosis following tissue injury. STATEMENT OF SIGNIFICANCE: We
      have previously demonstrated that poly(p-dioxanone-co-l-phenylalanine) (PDPA)
      could induce apoptosis to fibroblast and deduced that the inhibitory effect comes
      from l-phenylalanine. In present study, the inhibition mechanism of l
      phenylalanine on fibroblast proliferation was demonstrated. The calcium sensitive
      receptor (CaSR) was found to be the action site. The CaSR was downregulated after
      the application of l-phenylalanine, and then the ER Ca2+ stores were released.
      The released Ca2+ can simultaneously activate Ca2+/calcineurin and then trigger
      apoptosis and G1 arrest of fibroblast. Hence, l-phenylalanine could be seen as
      anti-fibrosis drug and PDPA which conjugate l-phenylalanine by hydrolytic
      covalent bonds could be seen as l-phenylalanine polymer prodrug. Based above, the
      in vivo anti-fibrotic function of PDPA were verified in three different animal
      models.

PMID- 29660511
TI  - Comparative adsorption profiles of basal lamina proteome and gingival cells onto
      dental and titanium surfaces.
AB  - : Titanium (Ti) dental implants are susceptible to bacterial infections and
      failure due to lack of proper epithelial seal. Epithelial cells establish a
      strong epithelial seal around natural teeth by the deposition of basal lamina
      (BL) proteins that adsorb on the tooth surface. This seal can even be re
      established onto cementum or dentin following injury or periodontal therapy.
      However, it is unclear how tooth surfaces promote this cell attachment and
      protein adsorption. Understanding the interactions between BL proteins and
      epithelial cells with dentin and Ti will facilitate the development of implant
      surfaces that promote the formation of an epithelial seal and improve the success
      of periodontal therapy and wound healing on natural teeth. To study these
      interactions, we used a surface proteomic approach to decipher the adsorption
      profile of BL proteins onto Ti and dentin, and correlated these adsorption
      profiles with in vitro interactions of human gingival fibroblasts and epithelial
      cells. Results showed that dentin adsorbed higher amounts of key BL proteins,
      particularly laminin and nidogen-1, and promoted more favorable interactions with
      epithelial cells than Ti. Next, dentin specimens were deproteinized or partially
      demineralized to determine if its mineral or protein component was responsible
      for BL adsorption and cell attachment. Deproteinized (mineral-rich) and partially
      demineralized (protein-rich) dentin specimens revealed BL proteins (i.e. laminin
      and nidogen-1) and epithelial cells interact preferentially with dentinal
      proteins rather than dentin mineral. These findings suggest that, unlike Ti,
      dentin and, in particular, dentinal proteins have a selective affinity to BL
      proteins that enhance epithelial cell attachment. STATEMENT OF SIGNIFICANCE: It
      is remains unclear why natural teeth, unlike titanium dental implants, promote
      the formation of an epithelial seal that protects them against the external
      environment. This study used a surface screening approach to analyze the
      adsorption of proteins produced by epithelial tissues onto tooth-dentin and
      titanium surfaces, and correlate it with the behaviour of cells. This study shows
      that tooth-dentin, in particular its proteins, has a higher selective affinity to
      certain adhesion proteins, and subsequently allows more favourable interactions
      with epithelial cells than titanium. This knowledge could help in developing new
      approaches for re-establishing and maintaining the epithelial seal around teeth,
      and could pave the way for developing implants with surfaces that allow the
      formation of a true epithelial seal.

PMID- 29660513
TI  - White-matter functional networks changes in patients with schizophrenia.
AB  - Resting-state functional MRI (rsfMRI) is a useful technique for investigating the
      functional organization of human gray-matter in neuroscience and neuropsychiatry.
      Nevertheless, most studies have demonstrated the functional connectivity and/or
      task-related functional activity in the gray-matter. White-matter functional
      networks have been investigated in healthy subjects. Schizophrenia has been
      hypothesized to be a brain disorder involving insufficient or ineffective
      communication associated with white-matter abnormalities. However, previous
      studies have mainly examined the structural architecture of white-matter using
      MRI or diffusion tensor imaging and failed to uncover any dysfunctional
      connectivity within the white-matter on rsfMRI. The current study used rsfMRI to
      evaluate white-matter functional connectivity in a large cohort of ninety-seven
      schizophrenia patients and 126 healthy controls. Ten large-scale white-matter
      networks were identified by a cluster analysis of voxel-based white-matter
      functional connectivity and classified into superficial, middle and deep layers
      of networks. Evaluation of the spontaneous oscillation of white-matter networks
      and the functional connectivity between them showed that patients with
      schizophrenia had decreased amplitudes of low-frequency oscillation and increased
      functional connectivity in the superficial perception-motor networks.
      Additionally, we examined the interactions between white-matter and gray-matter
      networks. The superficial perception-motor white-matter network had decreased
      functional connectivity with the cortical perception-motor gray-matter networks.
      In contrast, the middle and deep white-matter networks had increased functional
      connectivity with the superficial perception-motor white-matter network and the
      cortical perception-motor gray-matter network. Thus, we presumed that the
      disrupted association between the gray-matter and white-matter networks in the
      perception-motor system may be compensated for through the middle-deep white
      matter networks, which may be the foundation of the extensively disrupted
      connections in schizophrenia.

PMID- 29660512
TI  - Modeling white matter microstructure with fiber ball imaging.
AB  - Fiber ball imaging (FBI) provides a means of calculating the fiber orientation
      density function (fODF) in white matter from diffusion MRI (dMRI) data obtained
      over a spherical shell with a b-value of about 4000 s/mm2 or higher. By
      supplementing this FBI-derived fODF with dMRI data acquired for two lower b-value
      shells, it is shown that several microstructural parameters may be estimated,
      including the axonal water fraction (AWF) and the intrinsic intra-axonal
      diffusivity. This fiber ball white matter (FBWM) modeling method is demonstrated
      for dMRI data acquired from healthy volunteers, and the results are compared with
      those of the white matter tract integrity (WMTI) method. Both the AWF and the
      intra-axonal diffusivity obtained with FBWM are found to be significantly larger
      than for WMTI, with the FBWM values for the intra-axonal diffusivity being more
      consistent with recent results obtained using isotropic diffusion weighting. An
      important practical advantage of FBWM is that the only nonlinear fitting required
      is the minimization of a cost function with just a single free parameter, which
      facilitates the implementation of efficient and robust numerical routines.

PMID- 29660514
TI  - Early life predictors of brain development at term-equivalent age in infants born
      across the gestational age spectrum.
AB  - BACKGROUND: It is well established that preterm infants have altered brain
      development compared with full-term (FT; >=37 weeks' gestational age [GA])
      infants, however the perinatal factors associated with brain development in
      preterm infants have not been fully elucidated. In particular, perinatal
      predictors of brain development may differ between very preterm infants (VP; <32
      weeks' GA) and infants born moderate (MP; 32-33 weeks' GA) and late (LP; 34-36
      weeks' GA) preterm, but this has not been studied. This study aimed to
      investigate the effects of early life predictors on brain volume and
      microstructure at term-equivalent age (TEA; 38-44 weeks), and whether these
      effects differ for GA groups (VP, MP, LP or FT). METHODS: Structural images from
      328 infants (91 VP, 63 MP, 104 LP and 70 FT) were segmented into white matter,
      cortical grey matter, cerebrospinal fluid, subcortical grey matter, brainstem and
      cerebellum. Cortical grey matter and white matter images were analysed using
      voxel-based morphometry. Fractional anisotropy (FA), mean diffusivity (MD), axial
      diffusivity (AD) and radial diffusivity (RD) images from 361 infants (92 VP, 69
      MP, 120 LP and 80 FT) were analysed using Tract-Based Spatial Statistics.
      Relationships between early life predictors (birthweight standard deviation score
      [BWSDS], multiple birth, sex, postnatal growth and social risk) and global brain
      volumes were analysed using linear regressions. Relationships between early life
      predictors and regional brain volumes and diffusion measures were analysed using
      voxelwise non-parametric permutation testing. RESULTS: Male sex was associated
      with higher global volumes of all tissues and higher regional volumes throughout
      much of the cortical grey matter and white matter, particularly in the FT group.
      Male sex was also associated with lower FA and higher AD, RD and MD in the optic
      radiation, external and internal capsules and corona radiata, and these
      associations were generally similar between GA groups. Higher BWSDS was
      associated with higher global volumes of all tissues and higher regional volumes
      in much of the cortical grey matter and white matter in all GA groups, as well as
      higher FA and lower RD and MD in many major tracts (corpus callosum, optic
      radiation, internal and external capsules and corona radiata), particularly in
      the MP and LP groups. Multiple birth and social risk also showed associations
      with global and regional volumes and regional diffusion values which varied by GA
      group, but these associations were not independent of the other early life
      predictors. Postnatal growth was not associated with brain volumes or diffusion
      values. CONCLUSION: Early life predictors of brain volumes and microstructure at
      TEA include sex, BWSDS, multiple birth and social risk, which have different
      effects based on GA group at birth. This study improves knowledge of the
      perinatal factors associated with brain abnormalities in infants born across the
      prematurity spectrum.

PMID- 29660515
TI  - Aspergillus fumigatus viability drives allergic responses to inhaled conidia.
AB  - BACKGROUND: Aspergillus fumigatus-induced allergic airway disease has been shown
      to involve conidial germination in vivo, but the immunological mechanisms remain
      uncharacterized. OBJECTIVE: A subchronic murine exposure model was used to
      examine the immunological mediators that are regulated in response to either
      culturable or nonculturable A fumigatus conidia. METHODS: Female B6C3F1/N mice
      were repeatedly dosed via inhalation with 1 * 105 viable or heat-inactivated
      conidia (HIC), twice per week for 13 weeks (26 exposures). Control mice inhaled
      high-efficiency particulate arrestor-filtered air. The influence of A fumigatus
      conidial germination on the pulmonary immunopathological outcomes was evaluated
      by flow cytometry analysis of cellular infiltration in the airways, assessment of
      lung messenger RNA expression, quantitative proteomics, and histopathology of
      whole lung tissue. RESULTS: Repeated inhalation of viable conidia, but not HIC,
      resulted in allergic inflammation marked by vascular remodeling, extensive
      eosinophilia, and accumulation of alternatively activated macrophages (AAMs) in
      the murine airways. More specifically, mice that inhaled viable conidia resulted
      in a mixed TH1 and TH2 (IL-13) cytokine response. Recruitment of eosinophils
      corresponded with increased Ccl11 transcripts. Furthermore, genes associated with
      M2 or alternatively activated macrophage polarization (eg, Arg1, Chil3, and
      Retnla) were significantly up-regulated in viable A fumigatus-exposed mice. In
      mice inhaling HIC, CD4+ T cells expressing IFN-gamma (TH1) dominated the
      lymphocytic infiltration. Quantitative proteomics of the lung revealed metabolic
      reprogramming accompanied by mitochondrial dysfunction and endoplasmic reticulum
      stress stimulated by oxidative stress from repetitive microbial insult.
      CONCLUSION: Our studies demonstrate that A fumigatus conidial viability in vivo
      is critical to the immunopathological presentation of chronic fungal allergic
      disease.

PMID- 29660516
TI  - Molecular cloning and characterization of C1 tetrahydrofolate (C1-THF) synthase
      in Bombyx mori, silkworm.
AB  - Folate metabolism pathway is mainly associated with syntheses of nucleic acids
      and proteins as well as DNA methylation and repair. Cytoplasmic C1
      tetrahydrofolate (C1-THF) synthase is a central enzyme in folate metabolism and
      plays an important role in C1-THF conversion. The full-length sequence of
      silkworm (Bombyx mori) cytoplasmic C1-THF synthase (BmC1-THF synthase) gene
      including an open reading frame (ORF) of 932 amino acid residues was cloned.
      Phylogenetic analysis indicated that BmC1-THF synthase shares 84% and 81%
      identity with C1-THF synthase of Papilio Xuthus and Danaus plexippus,
      respectively. Conserved sequence analysis showed that the 330 to 710 amino acid
      residues of BmC1-THF synthase were highly conserved among various organisms.
      Recombinant BmC1-THF synthase protein with a molecular weight of about 105.5 kDa
      was expressed in E. coli cells and identified using SDS-PAGE and western blot
      analysis. The expression of BmC1-THF synthase gene in eight silkworm tissues
      revealed that BmC1-THF synthase gene is widely expressed in various tissues of
      silkworm and highly expressed in the fat body. The expression characteristics of
      BmC1-THF synthase gene in response to oxidative stress were conducted under
      phoxim and high temperature (30  degrees C) exposure. The results showed that the
      transcriptional level of BmC1-THF synthase gene was upregulated by 3.435-fold and
      6.845-fold after phoxim and high temperature (30  degrees C) exposure,
      respectively, indicating that BmC1-THF synthase gene may play a significant role
      in response of silkworm to oxidative stresses.

PMID- 29660517
TI  - CYP2D6 (C2850T, G1846A, C100T) polymorphisms, haplotypes and MDR analysis in
      predicting coronary artery disease risk in north-west Indian population: A case
      control study.
AB  - AIMS: The present study was aimed to evaluate the association of C2850T, G1846A
      and C100T polymorphisms of the CYP2D6 with coronary artery disease (CAD) in North
      West Indian population. METHODS: In this case-control study, 200 patients with
      CAD and 200 age-, gender- and ethnicity-matched healthy controls were genotyped
      for C2850T, G1846A and C100T polymorphisms of CYP2D6 using polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS:
      Genotype and allele distributions of C2850T and G1846A polymorphisms of the
      CYP2D6 were significantly different between cases and controls (p = 0.038, p =
      0.021; p = 0.048, p = 0.012, respectively) whereas the distribution of genotype
      and allele for C100T polymorphism did not differ significantly (p = 0.098, p =
      0.117, respectively). The 2850T and1846A variants were significantly associated
      with the increased risk of developing CAD, as observed from the odds ratios for
      the 2850 T/T and 1846 G/A genotypes (OR: 2.44, 95% CI: 1.99-4.99, p = 0.015 and
      OR: 1.62, 95% CI: 1.02-2.56, p = 0.041, respectively). Moreover, the recessive
      model in C2850T and the dominant model in G1846A are the best fit inheritance
      models to predict the susceptible gene effects (OR: 2. 07, 95% CI: 1.05-4.08, p =
      0.031 and OR: 1.70, 95% CI: 1.10-2.62, p = 0.016, respectively). On gender
      stratification, these associations were observed only in females in addition to
      the C/T genotype of C2850T (OR: 2.52, 95% CI: 1.42-4.38, p = 0.001) and C100T
      (OR: 3.18, 95% CI: 1.52-6.67, p = 0.002). Furthermore, it is also observed that
      the CAT (OR: 2. 61, 95% CI: 1.07-6.34, p = 0.035) and TAC (OR: 15. 22, 95% CI:
      1.97-117.58, p = 0.009) are high-risk haplotypes for CAD in the total group,
      whereas, the TGC (OR: 1. 64, 95% CI: 1.02-2.62, p = 0.042) and CAT (OR: 4. 21,
      95% CI: 1.12-15.59, p = 0.035) haplotypes provide gender-specific risk in
      females. CONCLUSIONS: Our results indicate significant association of C2850T,
      G1846A and C100T polymorphisms of CYP2D6 with CAD especially in females of North
      West Indian population.

PMID- 29660518
TI  - HOXB4 knockdown enhances the cytotoxic effect of paclitaxel and cisplatin by
      downregulating ABC transporters in ovarian cancer cells.
AB  - Therapeutic effects of anti-cancer drugs for ovarian cancer were limited due to
      the rapid development of chemotherapy resistance. The aim of this study was to
      test whether knockdown of Homeobox B4 (HOXB4) enhanced the cytotoxic effect of
      paclitaxel and cisplatin in ovarian cancer cells. HOXB4 expressions at mRNA and
      protein levels were upregulated in Taxol-resistant A2780 (A2780/Taxol) and DDP
      resistant SKOV-3 (SKOV-3/DDP) cells. HOXB4 knockdown enhanced the cytotoxic
      effects of Taxol and DDP in A2780/Taxol and SKOV-3/DDP cells, respectively. HOXB4
      silencing suppressed the phosphatidylinositol 3-kinase (PI3K)/Akt signaling
      pathway and reduced the expression of ABCB1, ABCC1 and ABCG2 in ovarian cancer
      cells. PI3K inhibitor LY294002 or siRNA targeting Akt (si-Akt) treatment
      inhibited cell viability, decreased protein levels of ABCB1, ABCC1 and ABCG2, and
      increased LDH release in A2780/Taxol and SKOV-3/DDP cells. These findings
      revealed that HOXB4 knockdown enhanced the cytotoxic effects of Taxol and DDP by
      downregulating ABC transporters via inhibiting the PI3K/Akt pathway in ovarian
      cancer cells.

PMID- 29660519
TI  - Oocyte maturation and origin of the germline as revealed by the expression of
      Nanos-like in the Pacific oyster Crassostrea gigas.
AB  - Nanos gene plays an important role in germline development in animals. However,
      the molecular mechanisms involved in germline development in Mollusca, the second
      largest animal phylum, are still poorly understood. Here we identified the Nanos
      orthologue from the Pacific oyster Crassostrea gigas (Cg-Nanos-like), and
      investigated the expression patterns of Nanos during gametogenesis and
      embryogenesis in C. gigas. Tissue expression analysis showed that Cg-Nanos-like
      was specifically expressed in female gonads. During the reproductive cycle, the
      expression of Cg-Nanos-like mRNA increased matching the seasonal development of
      the ovarian tissues in diploids, while the expression levels were significantly
      lower in the ovaries of sterile triploids compared to diploids. High expression
      of Cg-Nanos-like transcripts were detected in early embryonic stages, while the
      expression significantly dropped at gastrulation and was barely detectable in
      veliger stages. In situ hybridization showed that Cg-Nanos-like was expressed at
      different stages of developing oocytes, whereas positive signals were detected
      only in spermatogonia during the spermatogenic cycle. These findings indicated
      that Cg-Nanos-like was involved in the development of germ cells, and maintenance
      of oocyte maturation. In early embryogenesis, the transcripts were broadly
      expressed; following gastrulation, the expression was restricted to two cell
      clumps, which might be the putative primordial germ cells (PGCs) or their
      precursors. Based on the results, the formation of the PGCs in C. gigas was
      consistent with the model of transition from epigenesis to preformation.

PMID- 29660520
TI  - miR-758 mediates oxLDL-dependent vascular endothelial cell damage by suppressing
      the succinate receptor SUCNR1.
AB  - Atherosclerosis is a vascular disease associated with ageing, and its occurrence
      and development are closely related to the vascular inflammatory response.
      Oxidized low-density lipoprotein (oxLDL) has distinct effects in atherosclerosis.
      We aimed to determine the mechanisms underlying these effects. microRNAs
      including miR-758 were differentially expressed in oxLDL-treated HUVECs or HAECs.
      Luciferase reporter assay results indicated that SUCNR1 is an important target of
      miR-758. Expression of SUCNR1 and its downstream components was decreased
      significantly in ApoE-/- mice. Overexpression of miR-758 could suppress HUVEC
      proliferation by cell cycle arrest at the G0/G1 phase. miR-758 was overexpressed
      on HUVECs with markedly reduced capillary tubule formation capacity.
      Overexpression of miR-758 on HUVECs or HAECs could significantly reduce SUCNR1
      (GPR91), SATA3, phosphorylated STAT3 (p-STAT3), and EVGF levels. Thus, oxLDL
      likely damages vascular endothelial cells by modulating the DLK1-DIO3 genomic
      imprinted microRNA cluster component miR-758, thereby suppressing expression of
      SUCNR1/GPR91 and its downstream components.

PMID- 29660521
TI  - An investigation of oyster TGF-beta receptor genes and their potential roles in
      early molluscan development.
AB  - Though the roles of BMP signaling in development is studied extensively in
      insects and vertebrates, our knowledge of BMP signaling in molluscan development
      is limited. In the present study, we performed a genome-based analysis of TGF
      beta receptors in the Pacific oyster Crassostrea gigas and revealed that C. gigas
      possessed all five canonical members of the gene family, including three type I
      and two type II receptors. Whole mount in situ hybridization revealed that four
      receptor genes exhibited universal expression at the gastrula stage but cgi
      bmprII mRNA was only expressed at the anterior lip of blastopore, indicating the
      regulation of BMP signaling through restricted expression of TGF-beta receptors.
      Treatment of oyster embryos using a BMP signaling inhibitor (dorsomorphin)
      resulted in obvious changes of the expression of developmental regulatory genes.
      In particular, three dorsally expressed genes were inhibited and two genes
      expressed at the opposite side showed increased expression, indicating BMP
      signaling may function in dorsal-ventral (DV) patterning. Some of the influenced
      genes were potential shell-formation (pSF) genes, including the well-accepted pSF
      gene engrailed, and thus this indicates the development of shell field was
      affected by dorsomorphin treatment. Subsequent scanning electronic observation
      revealed morphological change of the posterior margin of the shell field. Taken
      together, these results indicate the roles of BMP signaling in both DV patterning
      and development of shell field in oyster embryo, which expands our knowledge of
      early molluscan development.

PMID- 29660523
TI  - Inhibition of quorum sensing-mediated virulence in Serratia marcescens by
      Bacillus subtilis R-18.
AB  - Serratia marcescens is an opportunistic human pathogen causing various nosocomial
      infections, most importantly urinary tract infections (UTIs). It exhibits
      increased resistance towards the conventional antibiotics. This study was aimed
      to evaluate the anti-virulence effect of a rhizosphere soil bacterium Bacillus
      subtilis strain R-18 against the uropathogen S. marcescens. First, the bacterial
      cell-free culture supernatant (CFCS) of B. subtilis strain R-18 was evaluated for
      its quorum sensing inhibitory (QSI) potential against biomarker strain
      Chromobacterium violaceum and the test pathogen S. marcescens. The B. subtilis R
      18 CFCS effectively inhibited the quorum sensing (QS)-mediated violacein pigment
      production in C. violaceum and prodigiosin pigment production in S. marcescens.
      Furthermore, B. subtilis R-18 CFCS was successively extracted with different
      solvent systems. Of these solvents, B. subtilis R-18 petroleum ether (PE) extract
      showed inhibition in biofilm formation, protease, lipase, and hemolysin
      productions in S. marcescens. Fourier transform infrared spectroscopic (FT-IR)
      analysis revealed the alterations in the cellular components of bacterial cell
      pellets obtained from B. subtilis R-18 PE extract treated and untreated S.
      marcescens. The differential gene expression study further validated the
      downregulation of virulence-associated genes. Characterization of the active
      principle in B. subtilis R-18 PE extract by gas chromatography-mass spectrometry
      (GC-MS) analysis showed the presence of multiple compounds with therapeutic
      values, which could possibly reduce the QS-dependent phenotypes in S. marcescens.

PMID- 29660522
TI  - Helicobacter pylori-derived heat shock protein 60 increases the induction of
      regulatory T-cells associated with persistent infection.
AB  - Local Treg responses are involved in Helicobacter pylori-related inflammation and
      clinical outcomes after infection, and H. pylori-derived HSP60 (HpHSP60) is an
      important virulence factor associated with gastric carcinogenesis. This study to
      investigate the role of HpHSP60 in immunosuppression, particularly with regard to
      whether it could induce the production of Treg cells. For this purpose, human
      peripheral blood mononuclear cells (PBMCs) were treated with or without HpHSP60
      in the presence of an anti-CD3 mAb to determine the effect of HpHSP60 on cell
      proliferation. In this report, HpHSP60 decreased the expression of CDK4 to
      significantly arrest the proliferation of mitogen-stimulated T-cells, which
      correlated with the induction of Treg cells. Moreover, monocytic cells were
      essential for the induction of HpHSP60-induced Treg cells via the secretion of IL
      10 and TGF-beta after treatment with HpHSP60. Blockage of HpHSP60 with specific
      monoclonal antibodies significantly reduced the colonization of H. pylori and the
      expression of Treg cells in vivo. Overall, our results suggest that HpHSP60 could
      act on macrophages to trigger the expression of IL-10 and TGF-beta, thereby
      leading to an increase in Treg cells and inhibition of T-cell proliferation.

PMID- 29660524
TI  - Temperature-dependent development of Asian citrus psyllid on various hosts, and
      mortality by two strains of Isaria.
AB  - The Asian citrus psyllid (ACP), Diaphorina citri Kuwayama (Hemiptera: Psyllidae)
      is a devastating pest of Citrus spp. The aim of present study was to investigate
      the development and mortality of ACP on citrus (Citrus sinensis) (healthy and
      Huanglongbing- (HLB) diseased) and jasmine (Murraya paniculata) plants at various
      temperatures. Two new Isaria strains were collected from citrus orchards of
      Fuzhou (China), and HLB-diseased plants were verified by running PCR for 16S gene
      of Candidatus Liberibacter asiaticus (CLas). Development observations were
      recorded for egg, nymph and adult stages on all plants and three different
      temperatures (20, 25 and 30  degrees C) whereas mortality observations were
      recorded for the nymph (fifth instar) and adults on all plants at 25  degrees C.
      Field collected Isaria strains were belonged to previously reported Chinese
      strains under Maximum Parsimony (MP) and Maximum Likelihood methods, as well as,
      CLas isolates were belonged to previously reported Chinese isolates under MP and
      Neighbor-Joining methods. The fastest development and mortality was observed on
      HLB-diseased plants whereas longest time was taken by development and mortality
      completion on jasmine plants at all temperatures. The fastest developmental times
      of egg, nymph (first to fourth and fifth instar) and adult stages were ranged
      from 3.02 to 3.72 d, to 7.63-9.3 d, 5.35-5.65 d and 24.46-28.47 d on HLB-diseased
      plants at 30-20  degrees C, respectively. On the other hand, I. javanica caused
      the fastest mortality of nymphs and adults (32.21 +/- 4.47% and 19.33 +/- 4.51%)
      on HLB-diseased plants with the concentration of 1 * 108 conidia.mL-1 after 3 d
      and 7 d, respectively. It is concluded that there is a need for extensive
      molecular work to understand the extra-development and mortality of ACP on
      diseased plants, because, CLas bacterium can be supportive to uptake more sap
      from plant phloem.

PMID- 29660525
TI  - Gastric Peroral Endoscopic Pyloromyotomy Reduces Symptoms, Increases Quality of
      Life, and Reduces Health Care Use For Patients With Gastroparesis.
AB  - BACKGROUND & AIMS: Gastric peroral endoscopic pyloromyotomy (GPOEM) is becoming a
      promising treatment option for patients with refractory gastroparesis. We aimed
      to systematically assess the efficacy of GPOEM and its effects on health care
      use. METHODS: We performed a retrospective study on 30 patients with refractory
      gastroparesis who underwent GPOEM from June 2015 through July 2017 at a tertiary
      center. We compared outcomes with those of 7 patients with refractory
      gastroparesis who did not undergo the procedure (controls). The primary outcomes
      were patient-reported reductions in symptoms, based on the gastroparesis cardinal
      symptom index (GCSI), and increases in 8 aspects of quality of life, based on
      Short Form 36 (SF-36) scores. Data were collected on the day of the procedure
      (baseline) and at 1 month, 6 months, 12 months, and 18 months afterward.
      Secondary outcomes included visits to the emergency department or hospitalization
      for gastroparesis-related symptoms. RESULTS: GPOEM was technically successful in
      all patients and significantly reduced GCSI scores in repeated-measure analysis
      of variance (F2.044, 38.838 = 22.319; P < .0005). The mean score at baseline was
      3.5 +/- 0.6, at 1 month after GPOEM was 1.8 +/- 1.0 (P < .0005), at 6 months
      after was 1.9 +/- 1.2 (P < .0005), at 12 months after was 2.6 +/- 1.5 (P < .026),
      and at 18 months after was 2.1 +/- 1.3 (P < .016). GPOEM was associated with
      improved quality of life: 77.8%, 76.5%, and 70% of patients had significant
      increases in SF-36 scores, compared with baseline, at 1 month, 6 months, and 12
      months after GPOEM, respectively (F1.71,18.83 = 14.16; P < .0005). Compared with
      controls, patients who underwent GPOEM had significant reductions in GCSI, after
      we controlled for baseline score and duration of the disease (F1,31 = 9.001; P =
      .005). Patients who received GPOEM had significant reductions in number of
      emergency department visits (from 2.2 +/- 3.1 times/mo at baseline to 0.3 +/- 0.8
      times/mo; P = .003) and hospitalizations (from 1.7 +/- 2 times/mo at baseline to
      0.2 +/- 0.4 times/mo; P = .0002). CONCLUSIONS: In a retrospective study of
      patients who underwent GPOEM for refractory gastroparesis, we found the procedure
      significantly improved symptoms, increased quality of life, and reduced health
      care use related to gastroparesis.

PMID- 29660526
TI  - Duodenal Scalloping Indicate Waldenstrom Macroglobulinemia.

PMID- 29660527
TI  - The Association Between Mutations in BRAF and Colorectal Cancer-Specific Survival
      Depends on Microsatellite Status and Tumor Stage.
AB  - BACKGROUND & AIMS: Colorectal tumors with mutations in BRAF and microsatellite
      stability (MSS) have been associated with adverse outcomes of patients. Combined
      tests for microsatellite instability-high (MSI-H) and BRAF mutations might
      therefore be used in risk assessment, particularly for patients with stage II
      tumors. We investigate the stage-specific prognostic value of combined testing
      for MSI-H and BRAF for patients with colorectal cancer. METHODS: We performed a
      retrospective analysis of colorectal tumor samples collected from 1995 patients
      at 22 hospitals in Germany, between 2003 and 2010. Samples were analyzed for MSI
      H using an established mononucleotide marker panel; BRAF mutations (BRAFV600E)
      were detected by Sanger sequencing or in tissue microarray blocks using
      immunohistochemistry. Cancers were assigned to categories of having MSS without
      mutations in BRAF, MSS with mutant BRAF, MSI-H without mutations in BRAF, and MSI
      H with mutant BRAF. We investigated the association between tumor categories with
      clinical and pathologic features and patient's overall, disease-specific, and
      recurrence-free survival (median follow-up time, 5.1 y). RESULTS: Tumors were
      stage I in 364 (18%), stage II in 678 (34%), stage III in 673 (34%), and stage IV
      (14%) in 280 patients. Sixty-three percent of tumors were located in the colon
      and 37% in the rectum. Most tumors (85%) had MSS without mutations in BRAF, 3%
      had MSS with mutant BRAF, 7% had MSI-H without mutations in BRAF, and 5% had MSI
      H with mutant BRAF. In patients whose tumors were MSI-H, mutation of BRAF did not
      significantly affect survival time. Patients whose tumors had MSS with mutant
      BRAF had significantly reduced overall survival (hazard ratio [HR], 2.16; 95% CI,
      1.54-3.04; P < .001), disease-specific survival (HR, 2.59; 95% CI, 1.77-3.79; P <
      .001), and recurrence-free survival (HR, 2.45; 95% CI, 1.70-3.52; P < .001) than
      patients whose tumors had MSS without BRAF mutation. Although BRAF mutations in
      tumors with MSS were associated with disease-specific survival of patients with
      stage III or IV tumors (P < .001), these features did not affect survival of
      patients with stage II tumors (P = .639). CONCLUSIONS: In an analysis of almost
      2000 patients with colorectal cancer, we found BRAF mutations to reduce survival
      of patients in stage III or IV (but not stage II) tumors with MSS. These findings
      do not support testing stage I or II colorectal tumors for BRAF mutations,
      although additional large studies are needed.

PMID- 29660528
TI  - Yield of Colonoscopy After a Positive Result From a Fecal Immunochemical Test OC
      Light.
AB  - BACKGROUND & AIMS: The fecal immunochemical test (FIT) is widely used in
      colorectal cancer (CRC) screening. The OC-Light FIT is 1 of 2 FITs recommended
      for CRC screening by the Preventive Services Task Force guidelines. However,
      little is known about its ability to detect CRC in large average-risk
      populations. METHODS: We performed a retrospective cohort study of patients (50
      75 years old) in the San Francisco Health Network who were screened for CRC by OC
      Light FIT from August 2010 through June 2015. Patients with a positive result
      were referred for colonoscopy. We used electronic health records to identify
      participants with positive FIT results, and collected results from subsequent
      colonoscopies and pathology analyses. The FIT positive rate was calculated by
      dividing the number of positive FIT results by the total number of FIT tests
      completed. The primary outcome was the positive rate from OC-Light FIT and yield
      of neoplasms at colonoscopy. Secondary outcomes were findings from first vs
      subsequent rounds of testing, and how these varied by sex and race. RESULTS: We
      collected result from 35,318 FITs, performed on 20,886 patients; 2930 patients
      (8.3%) had a positive result, and 1558 patients completed the follow-up
      colonoscopy. A positive result from the FIT identified patients with CRC with a
      positive predictive value of 3.0%, and patients with advanced adenoma with a
      positive predictive value of 20.8%. The FIT positive rate was higher during the
      first round of testing (9.4%) compared to subsequent rounds (7.4%) (P < .01). The
      yield of CRC in patients with a positive result from the first round of the FIT
      was 3.7%, and decreased to 1.8% for subsequent rounds (P = .02). CONCLUSIONS: In
      a retrospective analysis of patients in a diverse safety-net population who
      underwent OC-Light FIT for CRC screening, we found that approximately 3% of
      patients with a positive result from a FIT to have CRC and approximately 21% to
      have advanced adenoma.

PMID- 29660529
TI  - BmSUC1 is essential for glycometabolism modulation in the silkworm, Bombyx mori.
AB  - Sucrose is the most commonly transported sugar in plants and is easily
      assimilated by insects to fulfill the requirement of physiological metabolism.
      BmSuc1 is a novel animal beta-fructofuranosidase (beta-FFase, EC 3.2.1.26)
      encoding gene that was firstly cloned and identified in silkworm, Bombyx mori.
      BmSUC1 was presumed to play an important role in the silkworm-mulberry enzymatic
      adaptation system by effectively hydrolyzing sucrose absorbed from mulberry
      leaves. However, this has not been proved with direct evidence thus far. In this
      study, we investigated sucrose hydrolysis activity in the larval midgut of B.
      mori by inhibition tests and found that sucrase activity mainly stemmed from beta
      FFase, not alpha-glucosidase. Next, we performed shRNA-mediated transgenic RNAi
      to analyze the growth characteristics of silkworm larvae and variations in
      glycometabolism in vivo in transgenic silkworms. The results showed that in the
      RNAi-BmSuc1 transgenic line, larval development was delayed, and their body size
      was markedly reduced. Finally, the activity of several disaccharidases alone in
      the midgut and the sugar distribution, total sugar and glycogen in the midgut,
      hemolymph and fat body were then determined and compared. Our results
      demonstrated that silencing BmSuc1 significantly reduced glucose and apparently
      activated maltase and trehalase in the midgut. Together with a clear decrease in
      both glycogen and trehalose in the fat body, we conclude that BmSUC1 acts as an
      essential sucrase by directly modulating the degree of sucrose hydrolysis in the
      silkworm larval midgut, and insufficient sugar storage in the fat body may be
      responsible for larval malnutrition and abnormal petite phenotypes.

PMID- 29660531
TI  - Using auto population of X-ray procedure exam type in radiology reports to
      decrease reporting errors.

PMID- 29660530
TI  - Assessing patterns of T2/T1rho change in grade 1 cartilage lesions of the distal
      femur using an angle/layer dependent approach.
AB  - PURPOSE: To assess changes in the patterns of T2 and T1rho values within grade 1
      cartilage lesions of osteoarthritis (OA) patients compared to healthy controls.
      MATERIALS AND METHODS: Twenty healthy knees and 25 OA knees were examined on a 3
      T scanner. Areas of signal heterogeneity within the cartilage of the distal femur
      were identified using fat suppressed proton density-weighted imagines. T2 and
      T1rho values in each OA patient with grade 1 lesions were compared to average T2
      and T1rho values of the corresponding areas in healthy subjects. RESULTS: A total
      of 28 areas including grade 1 lesion were identified. Compared to normal
      cartilage, the majority of grade 1 cartilage lesions demonstrated either no
      significant change or a statistically significant increase in both T2 values
      (18/28, 64%) and T1rho values (23/28, 82%). Compared to T2, T1rho demonstrated a
      greater proportion of statistically significantly higher values in OA patients
      than those from the normal controls. However, T2 and T1rho values in grade 1
      lesions can be decreased, or demonstrate mixed patterns compared to those in
      healthy cartilage. CONCLUSION: Our results suggest that early degenerative
      cartilage lesions can demonstrate various patterns of T2 and T1rho changes.

PMID- 29660532
TI  - Imaging in testicular epidermoid cysts.
AB  - OBJECTIVE: To evaluate the utility of findings on ultrasound and magnetic
      resonance imaging (MRI) for the preoperative diagnosis of testicular epidermoid
      cysts (TEC). METHODS: The medical records of five patients treated for TEC at our
      institution between July 2010 and May 2017 were retrospectively reviewed.
      RESULTS: Imaging revealed a target or onion skin appearance on ultrasonography
      and MRI. Pathological examinations showed "bread slag-like" materials within the
      TEC. Lesions failed to demonstrate enhancement after Gd-DTPA injection.
      CONCLUSION: In the cases of TEC in the current study, accurate diagnosis ensured
      enucleation of the testicular cyst was performed rather than testicular
      resection.

PMID- 29660533
TI  - Role of lysophosphatidic acid in the retinal pigment epithelium and
      photoreceptors.
AB  - The human retina is a complex structure of organised layers of specialised cells
      that support the transmission of light signals to the visual cortex. The
      outermost layer of the retina, the retinal pigment epithelium (RPE), forms part
      of the blood retina barrier and is implicated in many retinal diseases.
      Lysophosphatidic acid (LPA) is a bioactive lipid exerting pleiotropic effects in
      various cell types, during development, normal physiology and disease. Its
      producing enzyme, AUTOTAXIN (ATX), is highly expressed by the pigmented epithelia
      of the human eye, including the RPE. Using human pluripotent stem cell (hPSC)
      derived retinal cells, we interrogated the role of LPA in the human RPE and
      photoreceptors. hPSC-derived RPE cells express and synthesize functional ATX,
      which is predominantly secreted apically of the RPE, suggesting it acts in a
      paracrine manner to regulate photoreceptor function. In RPE cells, LPA regulates
      tight junctions, in a receptor-dependent mechanism, with an increase in OCCLUDIN
      and ZONULA OCCLUDENS (ZO)-1 expression at the cell membrane, accompanied by an
      increase in the transepithelial resistance of the epithelium. High concentration
      of LPA decreases phagocytosis of photoreceptor outer segments by the RPE. In hPSC
      derived photoreceptors, LPA induces morphological rearrangements by modulating
      the actin myosin cytoskeleton, as evidenced by Myosin Light Chain l membrane
      relocation. Collectively, our data suggests an important role of LPA in the
      integrity and functionality of the healthy retina and blood retina barrier.

PMID- 29660534
TI  - Influence of copper(II) ions on the noncovalent interactions between cytidine-5'
      diphosphate or cytidine-5'-triphosphate and biogenic amines putrescine or
      spermidine.
AB  - Potentiometric and NMR spectroscopic studies of the nucleotide (NucP)/polyamine
      (PA) system (where NucP = CDP, CTP, PA = putrescine or spermidine) revealed the
      formation of molecular complexes (NucP)(Hx+y)(PA) (where Hx+y = number of
      protons; x - from NucP and y - from PA). Their thermodynamic parameters were
      determined and the modes of their interactions were proposed. The main reaction
      centers were found to be the protonated amine groups of polyamine (positive
      centers) and phosphate groups of nucleotide (negative centers). The pH ranges in
      which the complex occurs correspond to those of amine protonation and -PO3x-
      group deprotonation, which unambiguously confirms the dipole-dipole type of
      interaction. In the pH range of total deprotonation of NHx+ groups from the
      polyamine, the molecular complexes disappear. The equilibrium and spectroscopic
      studies of the ternary systems Cu(II)/NucP/PA evidenced the formation of
      Cu(NucP)Hx+y(PA) type coordination compounds and Cu(NucP)?(PA)(Hx) type molecular
      complexes with polyamine in the outer coordination sphere. The main sites of
      metal ion bonding in the latter species are the phosphate groups of the
      nucleotide, while in the coordination compounds - besides the phosphate groups -
      also the donor nitrogen atoms from the polyamines. In this paper we have also
      quantitatively calculated the effect of metal ions on the formation of the
      molecular complexes.

PMID- 29660535
TI  - Turf soil enhances treatment efficiency and performance of phenolic wastewater in
      an up-flow anaerobic sludge blanket reactor.
AB  - Phenols are industrially generated intermediate chemicals found in wastewaters
      that are considered a class of environmental priority pollutants. Up-flow
      anaerobic sludge blanket (UASB) reactors are used for phenolic wastewater
      treatment and exhibit high volume loading capability, favorable granule settling,
      and tolerance to impact loads. Use of support materials can promote biological
      productivity and accelerate start-up period of UASB. In the present study, turf
      soil was used as a support material in a mesophilic UASB reactor for the removal
      of phenols in wastewater. During sludge acclimatization (45-96 days), COD and
      phenols in the treatments were both reduced by 97%, whereas these contents in the
      controls were decreased by 81% and 75%, respectively. The phenol load threshold
      for the turf soil UASB reactor was greater (1200 mg/L, the equivalent of COD 3000
      mg/L) in comparison with the control UASB reactor (900 mg/L, the equivalent of
      COD 2250 mg/L) and the turf soil UASB reactor was also more resistant to shock
      loading. Improved sludge settling, shear resistance, and higher biological
      activity occurred with the turf soil UASB reactor due to the formation of large
      granular sludge (0.6 mm or larger) in higher relative percentages. Granular
      sludge size was further enhanced by the colonization of filamentous bacteria on
      the irregular surface of the turf soil.

PMID- 29660536
TI  - Effect of asymmetric wettability in nanofiber membrane by electrospinning
      technique on separation of oil/water emulsion.
AB  - Oil/water separation is an important issue in the environmental field because of
      increasing worldwide oil pollution. In particular, emulsion under 20 MUm in size
      causes a serious problem in water treatment. Thus, development of an effective
      oil/water emulsion separation membrane is required. Asymmetric wettability is one
      effective technique for emulsion separation due to its directional liquid
      transport property. In this research, wettability was controlled by adjusting the
      diameter of an electrospun nanofiber for a difference in surface roughness.
      Through analysis of the surface structure and contact angle of nanofibers with
      various diameters, the contact angles of fibers with different diameters were
      increased about 40 degrees  to confirm that surface structure affects surface
      wettability. Comparison of asymmetric wettability membranes (AwENMs) and a single
      membrane (ENM) for oil/water emulsion separation shows that AwENMs perform about
      two times faster and reject 10% of emulsion.

PMID- 29660537
TI  - Where does the toxicity come from in saponin extract?
AB  - Saponin-rich plant extracts contain bioactive natural compounds and have many
      applications, e.g. as biopesticides and biosurfactants. The composition of
      saponin-rich plant extracts is very diverse, making environmental monitoring
      difficult. In this study various ecotoxicity data as well as exposure data have
      been collected to explore which compounds in the plant extract are relevant as
      plant protection agents and furthermore to clarify which compounds may cause
      undesired side-effects due to their toxicity. Hence, we quantified the toxicity
      of different fractions (saponins/non-saponins) in the plant extracts on the
      aquatic crustacean Daphnia magna and zebrafish (Danio rerio) embryos. In
      addition, we tested the toxicity changes during saponin degradation as well. The
      results confirm that saponins are responsible for the majority of toxicity (85.1
      93.6%) of Quillaja saponaria extract. We, therefore, suggest saponins to be the
      main target of saponin-rich plant extracts, for instance in the saponin-based
      biopesticide regulation. Furthermore, we suggest that an abundant saponin
      fraction, QS-18 from Q. saponaria, can be a key monitoring target to represent
      the environmental concentration of the saponins, as it contributes with 26% and
      61% of the joint toxicity to D. magna and D. rerio, respectively out of the total
      saponins. The degradation products of saponins are 3-7 times less toxic than the
      parent compound; therefore the focus should be mainly on the parent compounds.

PMID- 29660538
TI  - A modified two-point titration method for the determination of volatile fatty
      acids in anaerobic systems.
AB  - The volatile fatty acids (VFA) concentration plays important roles in the rapid
      start-up and stable operation of anaerobic reactors. It's essential to develop a
      simple and accurate method to monitor the VFA concentration in the anaerobic
      systems. In present work, a modified two-point titration method was developed to
      determine the VFA concentration. The results show that VFA concentration in
      standard solutions estimated by the titration method coincided well with that
      measured by gas chromatograph, where all relative errors were lower than 5.5%.
      Compared with the phosphate, ammonium and sulfide subsystems, the effect of
      bicarbonate on the accuracy of the developed method was relatively significant.
      When the bicarbonate concentration varied from 0 to 8 mmol/L, the relative errors
      increased from 1.2% to 30% for VFA concentration at 1 mmol/L, but were within
      2.0% for that at 5 mmol/L. In addition, the VFA composition affected the accuracy
      of the titration method to some extent. This developed titration method was
      further proved to be effective with practical effluents from a lab-scale
      anaerobic reactor under organic shock loadings and an unstable full-scale
      anaerobic reactor.

PMID- 29660539
TI  - Oxidation of acetone over Co-based catalysts derived from hierarchical layer
      hydrotalcite: Influence of Co/Al molar ratios and calcination temperatures.
AB  - In order to enhance catalytic performance for acetone, Co-based catalysts
      prepared under different Co/Al molar ratios and calcination temperatures have
      been studied in this work. The results indicated that the catalytic activities of
      the catalysts firstly increased and then decreased with the increase of the Co/Al
      molar ratio and decreased with the increase of the calcination temperature. Based
      on the catalytic activities, TG/DTA, XRD, TPR and XPS characterization results,
      it can be found that catalytic activities of the catalysts with various Co/Al
      molar ratios were effected by the good crystallization structure of catalyst
      precursor, surface Co3+/Co2+ molar ratio, low temperature reducibility, and
      Oads/Olatt molar ratio of the catalysts. Meanwhile, the catalytic activities of
      the catalysts with different calcination temperatures depended on the low
      temperature reducibility, surface Co3+/Co2+ molar ratio, porous structure and
      crystallization structure of the catalyst. Among different synthetic composition,
      5:1 CoAlO-300 catalyst (T90% = 225  degrees C) and 5:1 CoAlO-200 catalyst (T90% =
      222  degrees C) exhibited the efficient acetone oxidation.

PMID- 29660540
TI  - The persistence of a broad range of antibiotics during calve, pig and broiler
      manure storage.
AB  - After administration to livestock, a large fraction of antibiotics are excreted
      unchanged via excreta and can be transferred to agricultural land. For effective
      risk assessment a critical factor is to determine which antibiotics can be
      expected in the different environmental compartments. After excretion, the first
      relevant compartment is manure storage. In the current study, the fate of a broad
      scope of antibiotics (n = 46) during manure storage of different livestock
      animals (calves, pigs, broilers) was investigated. Manure samples were fortified
      with antibiotics and incubated during 24 days. Analysis was carried out by LC-MS.
      The dissipation of the antibiotics was modelled based on the recommendations of
      FOCUS working group. Sulphonamides relatively quickly dissipate in all manure
      types, with a DT90 of in general between 0.2 and 30 days. Tetracyclines (DT90 up
      to 422 days), quinolones (DT90 100-5800 days), macrolides (DT90 18-1000 days),
      lincosamides (DT90 135-1400 days) and pleuromutilins (DT90 of 49-1100 days) are
      in general much more persistent, but rates depend on the manure type.
      Specifically lincomycin, pirlimycin, tiamulin and most quinolones are very
      persistent in manure with more than 10% of the native compound remaining after a
      year in most manure types. For all compounds tested in the sub-set, except the
      macrolides, the dissipation was an abiotic process. Based on the persistence and
      current frequency of use, oxytetracycline, doxycycline, flumequine and tilmicosin
      can be expected to end up in environmental compartments. Ecotoxicological data
      should be used to further prioritize these compounds.

PMID- 29660541
TI  - How to reconcile wood production and biodiversity conservation? The Pan-European
      boreal forest history gradient as an "experiment".
AB  - There are currently competing demands on Europe's forests and the finite
      resources and services that they can offer. Forestry intensification that aims at
      mitigating climate change and biodiversity conservation is one example. Whether
      or not these two objectives compete can be evaluated by comparative studies of
      forest landscapes with different histories. We test the hypothesis that
      indicators of wood production and biodiversity conservation are inversely related
      in a gradient of long to short forestry intensification histories. Forest
      management data containing stand age, volume and tree species were used to model
      the opportunity for wood production and biodiversity conservation in five north
      European forest regions representing a gradient in landscape history from very
      long in the West and short in the East. Wood production indicators captured the
      supply of coniferous wood and total biomass, as well as current accessibility by
      transport infrastructure. Biodiversity conservation indicators were based on
      modelling habitat network functionality for focal bird species dependent on
      different combinations of stand age and tree species composition representing
      naturally dynamic forests. In each region we randomly sampled 25 individual 100
      km2 areas with contiguous forest cover. Regarding wood production, Sweden's
      Bergslagen region had the largest areas of coniferous wood, followed by Vitebsk
      in Belarus and Zemgale in Latvia. NW Russia's case study regions in Pskov and
      Komi had the lowest values, except for the biomass indicator. The addition of
      forest accessibility for transportation made the Belarusian and Swedish study
      region most suitable for wood and biomass production, followed by Latvia and two
      study regions in NW Russian. Regarding biodiversity conservation, the overall
      rank among regions was opposite. Mixed and deciduous habitats were functional in
      Russia, Belarus and Latvia. Old Scots pine and Norway spruce habitats were only
      functional in Komi. Thus, different regional forest histories provide different
      challenges in terms of satisfying both wood production and biodiversity
      conservation objectives in a forest management unit. These regional differences
      in northern Europe create opportunities for exchanging experiences among
      different regional contexts about how to achieve both objectives. We discuss this
      in the context of land-sharing versus land-sparing.

PMID- 29660542
TI  - Time to stop mucking around? Impacts of underwater photography on cryptobenthic
      fauna found in soft sediment habitats.
AB  - Scuba diving tourism is a sustainable source of income for many coastal
      communities, but can have negative environmental impacts if not managed
      effectively. Diving on soft sediment habitats, typically referred to as 'muck
      diving', is a growing multi-million dollar industry with a strong focus on
      photographing cryptobenthic fauna. We assessed how the environmental impacts of
      scuba divers are affected by the activity they are engaged in while diving and
      the habitat they dive in. To do this, we observed 66 divers on coral reefs and
      soft sediment habitats in Indonesia and the Philippines. We found diver activity,
      specifically interacting with and photographing fauna, causes greater
      environmental disturbances than effects caused by certification level, gender,
      dive experience or age. Divers touched the substrate more often while diving on
      soft sediment habitats than on coral reefs, but this did not result in greater
      environmental damage on soft sediment sites. Divers had a higher impact on the
      substrate and touch animals more frequently when observing or photographing
      cryptobenthic fauna. When using dSLR-cameras, divers spent up to five times
      longer interacting with fauna. With the unknown, long-term impacts on
      cryptobenthic fauna or soft sediment habitats, and the increasing popularity of
      underwater photography, we argue for the introduction of a muck diving code of
      conduct.

PMID- 29660543
TI  - Scalp cooling successfully prevents alopecia in breast cancer patients undergoing
      anthracycline/taxane-based chemotherapy.
AB  - INTRODUCTION: Chemotherapy for breast cancer induces alopecia, representing a
      major source of patient distress. This study assesses whether a scalp-cooling
      device is effective in reducing chemotherapy-induced alopecia, and assesses
      adverse treatment effects. MATERIALS AND METHODS: A prospective observational
      study including women with breast cancer undergoing chemotherapy and scalp
      cooling using a Paxman device. The primary efficacy end points were: successful
      hair preservation (no hair loss; <30% hair loss not requiring a wig; or <50% hair
      loss not requiring a wig) at the completion of chemotherapy. Secondary end points
      included adverse effects such as headache, pain, nausea or dizziness. RESULTS:
      The study enrolled 131 participants. Mean patient age was 49.8 years; 74%
      received anthracycline/taxane-based chemotherapy and 26% received taxane
      monotherapy based chemotherapy. Hair preservation was successful in 102 women who
      underwent scalp cooling (71.0%; 95% CI = 63-79%). Only adverse events related to
      device use were collected, representing 7% (95% CI = 3-11%) of cases.
      CONCLUSIONS: Scalp cooling is effective in preventing hair loss among breast
      cancer patients undergoing standard chemotherapy treatment, and has minimal
      adverse effects.

PMID- 29660544
TI  - Visible and near infrared spectroscopy as an authentication tool: Preliminary
      investigation of the prediction of the ageing time of beef steaks.
AB  - Visible-near infrared spectroscopy (Vis-NIRS) has been suggested to have
      potential for authentication of food products. The aim of the present preliminary
      study was to assess if this technology can be used to authenticate the ageing
      time (3, 7, 14 and 21 days post mortem) of beef steaks from three different
      muscles (M. Longissimus thoracis, M. Gluteus medius and M. Semitendinosus).
      Various mathematical pre-treatments were applied to the spectra to correct
      scattering and overlapping effects, and then partial least squares-discrimination
      analysis (PLS-DA) procedures applied. The best models were specific for each
      muscle, and the ability of prediction of ageing time was validated using full
      (leave-one-out) cross-validation, whereas authentication performance was
      evaluated using the parameters of sensitivity, specificity and overall correct
      classification. The results indicate that overall correct classification ranging
      from 94.2 to 100% was achieved, depending on the muscle. In conclusion, Vis-NIRS
      technology seems a valid tool for the authentication of ageing time of beef
      steaks.

PMID- 29660545
TI  - The effect of packaging on consumer eating quality of beef.
AB  - This experiment examined 3 packaging systems: overwrap packaging using oxygen
      permeable film (OWP); vacuum skin packaging (VSP) and modified atmosphere
      packaging (MAP, 80%O2 and 20%CO2) on consumer sensory. Three primals from 48
      carcasses were aged in vacuum packs for 5, 12 or 40 days. Steaks from longissimus
      lumborum, gluteus medius and psoas major muscles were packed in OWP, VSP and MAP
      for 9 days. Untrained consumers scored grilled steaks for tenderness, juiciness,
      liking of flavour and overall acceptability. Steaks in MAP had 10-12 points lower
      sensory scores (on a 100 point scale) compared to the OWP, or VSP systems (P <
      0.001). The packaging effect was independent of days aging and muscle. It was
      concluded that high oxygen MAP has the potential to be included as an input
      variable in the Meat Standards Australia beef grading model. This would be
      contingent upon research into when the MAP effect occurred and the effect of
      using different gas mixtures on eating quality.

PMID- 29660546
TI  - Structure and gene cluster of the O-antigen of Escherichia coli O54.
AB  - Mild acid hydrolysis of the lipopolysaccharide of Escherichia coli O54 afforded
      an O-polysaccharide, which was studied by sugar analysis, solvolysis with
      anhydrous trifluoroacetic acid, and 1H and 13C NMR spectroscopy. Solvolysis
      cleaved predominantly the linkage of beta-d-Ribf and, to a lesser extent, that of
      beta-d-GlcpNAc, whereas the other linkages, including the linkage of alpha-l
      Rhap, were stable under selected conditions (40  degrees C, 5 h). The following
      structure of the O-polysaccharide was established: ->4)-alpha-d-GalpA-(1 -> 2)
      alpha-l-Rhap-(1 -> 2)-beta-d-Ribf-(1 -> 4)-beta-d-Galp-(1 -> 3)-beta-d-GlcpNAc-(1
      > The O-antigen gene cluster of E. coli O54 was analyzed and found to be
      consistent in general with the O-polysaccharide structure established but there
      were two exceptions: i) in the cluster, there were genes for phosphoserine
      phosphatase and serine transferase, which have no apparent role in the O
      polysaccharide synthesis, and ii) no ribofuranosyltransferase gene was present in
      the cluster. Both uncommon features are shared by some other enteric bacteria.

PMID- 29660547
TI  - Surgical Treatment of Large or Giant Fusiform Middle Cerebral Artery Aneurysms: A
      Case Series.
AB  - BACKGROUND: Management of large or giant fusiform middle cerebral artery (MCA)
      aneurysms represents a significant challenge. OBJECTIVE: To describe the authors'
      experience in the treatment of large or giant fusiform MCA aneurysm by using
      various surgical techniques. METHODS: We retrospectively reviewed a database of
      aneurysms treated at our division between 2015 and 2017. RESULTS: Overall, 20
      patients (11 males, 9 females) were identified, with a mean age of 40.7 years
      (range, 13-65 years; median, 43 years). Six patients (30%) had ruptured aneurysms
      and 14 (70%) had unruptured aneurysms. The mean aneurysm size was 19 mm (range,
      10-35 mm). The aneurysms involved the prebifurcation in 5 cases, bifurcation in 4
      cases, and postbifurcation in 11 cases. The aneurysms were treated by clip
      reconstruction (n = 5), clip wrapping (n = 1), proximal occlusion or trapping (n
      = 4), and bypass revascularization (n = 10). Bypasses included 7 low-flow
      superficial temporal artery-MCA bypasses, 2 high-flow extracranial-intracranial
      bypasses, and 1 intracranial-intracranial bypass (reanastomosis). Bypass patency
      was 90%. Nineteen aneurysms (95%) were completely obliterated, and no
      rehemorrhage occurred during follow-up. There was no procedural-related
      mortality. Clinical outcomes were good (modified Rankin Scale score <=2) in 18 of
      20 patients (90%) at the last follow-up. CONCLUSIONS: Surgical treatment strategy
      for large or giant fusiform MCA aneurysms should be determined on an individual
      basis, based on aneurysm morphology, location, size, and clinical status.
      Favorable outcomes can be achieved by various surgical techniques, including clip
      reconstruction, wrap clipping, aneurysm trapping, aneurysm excision followed by
      reanastomosis, and partial trapping with bypass revascularization.

PMID- 29660548
TI  - How to Deal with the Empty Space After Organ Removal for Transplantation: A
      Single Medical Center Experience.
AB  - OBJECTIVE: Dealing with the empty space after organ removal for transplantation
      has not been investigated. METHODS: From January 28, 2005, to November 21, 2017,
      111 organ donors were enrolled in this study. They were divided into 3 groups: no
      replacement, replaced with paper printed with organ graphics, or replaced with 3
      dimensional (3D) printed simulated organs. The organs were removed at different
      periods. The donor's age, gender, etiology of admission, characteristics,
      clinical pictures, time interval between admission and date of donation, and time
      interval between donor coordinator consultations were evaluated. RESULTS: A total
      of 82 men and 29 women with mean age of 43 +/- 15.1 years were enrolled. Overall,
      329 organs and 126 corneas were transplanted. The major causes of brain death
      were traumatic brain injury (44.1%) and cerebrovascular disease (32.4%). Twelve
      donors initially presented with out-of-hospital cardiac arrest. Ten patients with
      solid cancers and 3 with septic shock donated both of their corneas. The mean
      time interval between donor coordinator and social worker consultation to organ
      donation was 3 (2-5 days) (median [interquartile range]). Periods I and II
      averaged 7-8 donors per year. Fourteen donors and 41 organs were replaced with 3D
      printed simulated organs at the families' request in 1 year. CONCLUSIONS: This is
      the first study to provide a replacement method dealing with the empty space
      after organ removal. We used 3D-printed simulated organs in addition to providing
      grief assistance and spiritual support. It also has the potential effect of
      increasing the organ donation rate.

PMID- 29660549
TI  - Perineural Spread Along Spinal and Obturator Nerves in Primary Vaginal Carcinoma:
      A Case Report.
AB  - BACKGROUND: Perineural spread is not an uncommon feature in carcinoma of the head
      and neck. On the contrary, perineural spread in pelvic malignancies has been
      rarely reported. This is the first report on perineural spread of the obturator
      nerve and the lumbosacral plexus from primary vaginal cancer. CASE DESCRIPTION: A
      50-year-old woman diagnosed with infectious spondylitis at an outside hospital
      was referred to our institution. She presented with persistent lower back pain
      and right anterior thigh pain. Magnetic resonance imaging and subsequent 18F
      fluorodeoxyglucose-positron emission tomography/computed tomography revealed
      primary vaginal cancer with metastatic lymphadenopathy and perineural spread of
      the lumbosacral plexus, including L3, L4 nerve roots and branches, and obturator
      nerve along with soft tissue masses in the right psoas and proximal adductor
      muscles. CONCLUSIONS: Clinical diagnosis of perineural spread in pelvic
      malignancies is difficult to establish, as it has nonspecific symptoms as an
      initial manifestation. Clinicians should recognize the possibility of perineural
      spread of malignancies if radiologic findings, such as thickening of lumbosacral
      nerves and perineural mass, are observed on magnetic resonance imaging. Further
      evaluation is necessary to detect possible pelvic malignancy and differentiate
      from other diseases.

PMID- 29660550
TI  - Mechanism for the Rapid Spontaneous Resolution of an Acute Subdural Hematoma and
      Transformation into a Subdural Hygroma.
AB  - BACKGROUND: Spontaneous resolution of acute subdural hematomas (SDHs), occurring
      as the result of a traumatic injury, is well reported in the literature and
      rapidly resolving SDHs have been reported as well. Although the mechanism behind
      the rapid resolution of a SDH has not been well understood, there are postulated
      mechanisms for this phenomenon. The aim of this report is to present a patient
      who experienced the rapid resolution of a traumatic SDH, which was replaced by a
      subdural hygroma. CASE DESCRIPTION: This 25-year-old man presented to the
      hospital with an acute left-sided SDH after a head-on motor vehicle collision. At
      the time of presentation, the patient had an acute SDH with 11 mm of midline
      shift. The hematoma resolved spontaneously within 48 hours and was replaced by a
      thin subdural hygroma. CONCLUSIONS: Rapidly resolving SDHs represent a phenomenon
      that has been well described, although is not entirely understood. The imaging
      findings of this patient suggest that cerebrospinal fluid washout is a mechanism
      that promotes acute SDH resolution.

PMID- 29660551
TI  - Photogrammetry of the Human Brain: A Novel Method for Three-Dimensional
      Quantitative Exploration of the Structural Connectivity in Neurosurgery and
      Neurosciences.
AB  - BACKGROUND: Anatomic awareness of the structural connectivity of the brain is
      mandatory for neurosurgeons, to select the most effective approaches for brain
      resections. Although standard microdissection is a validated technique to
      investigate the different white matter (WM) pathways and to verify the results of
      tractography, the possibility of interactive exploration of the specimens and
      reliable acquisition of quantitative information has not been described.
      Photogrammetry is a well-established technique allowing an accurate metrology on
      highly defined three-dimensional (3D) models. The aim of this work is to propose
      the application of the photogrammetric technique for supporting the 3D
      exploration and the quantitative analysis on the cerebral WM connectivity.
      METHODS: The main perisylvian pathways, including the superior longitudinal
      fascicle and the arcuate fascicle were exposed using the Klingler technique. The
      photogrammetric acquisition followed each dissection step. The point clouds were
      registered to a reference magnetic resonance image of the specimen. All the
      acquisitions were coregistered into an open-source model. RESULTS: We analyzed 5
      steps, including the cortical surface, the short intergyral fibers, the indirect
      posterior and anterior superior longitudinal fascicle, and the arcuate fascicle.
      The coregistration between the magnetic resonance imaging mesh and the point
      clouds models was highly accurate. Multiple measures of distances between
      specific cortical landmarks and WM tracts were collected on the photogrammetric
      model. CONCLUSIONS: Photogrammetry allows an accurate 3D reproduction of WM
      anatomy and the acquisition of unlimited quantitative data directly on the real
      specimen during the postdissection analysis. These results open many new
      promising neuroscientific and educational perspectives and also optimize the
      quality of neurosurgical treatments.

PMID- 29660552
TI  - Cervical Spine and Cord Angle Mismatch in the Pathogenesis of Myelopathy.
AB  - BACKGROUND: Cervical myelopathy is a complex pathology and dynamic compression of
      the tethered cervical cord, which may be responsible for clinical symptoms.
      METHODS: Patients with cervical canal stenosis who had magnetic resonance imaging
      in flexion and extension positions were retrospectively reviewed. All cases were
      evaluated in Nurick grade. The cervical parameters-cervical cord (CC) angle,
      cervical lordosis, and spine/cord (S/C) angle ratio-were measured on the magnetic
      resonance imaging. Mean values of these parameters were compared between
      nonmyelopathic (Nurick grade 0) and myelopathic groups (Nurick grades 1-5). A
      multinomial ordinal logistic regression was used to predict outcome for Nurick
      grade using the CC angle, the cervical lordosis angle, and the S/C angle ratio as
      independent variables. RESULTS: A total of 65 patients (35 men) with the mean age
      of 58.6 +/- 11.4 years were analyzed. A comparison of means between Nurick grade
      0 against each of myelopathic grades 1-5 revealed significant differences only
      for the S/C angle ratio. A cumulative comparison between nonmyelopathic and
      myelopathic grades for the S/C angle ratio showed significant difference of 0.29
      (1.16 +/- 0.5 vs. 1.45 +/- 0.6, respectively; P < 0.05). Cumulative comparison
      for the CC angle difference in flexion and extension lordosis did not show
      substantial differences. The S/C angle ratio was the only significant parameter
      in the prediction of the Nurick grade with an odds ratio of 2.63 (95% confidence
      interval 2.11-2.79). CONCLUSIONS: A positive correlation between Nurick grade and
      cervical spine and cord angle mismatch was found.

PMID- 29660553
TI  - A Novel Targeted Foraminoplasty Device Improves the Efficacy and Safety of
      Foraminoplasty in Percutaneous Endoscopic Lumbar Discectomy: Preliminary Clinical
      Application of 70 Cases.
AB  - OBJECTIVE: Percutaneous endoscopic lumbar discectomy (PELD) has become a mature
      and mainstream surgical technique for treating lumbar disc herniation (LDH);
      however, there is a steep learning curve with PELD, especially for puncture and
      foraminoplasty. In this study, we assessed the outcome and safety of a novel
      quantificational and targeted foraminoplasty device named ZESSYS for LDH.
      METHODS: From September to December of 2016, 70 patients with symptomatic LDH
      were enrolled in the study. The patients were assigned randomly to either the
      ZESSYS group or the conventional TESSYS group. We recorded the cannula
      introduction time, decompression time, radiation exposure time, intraoperative
      pain feeling score, visual analog scale, Oswestry Disability Index, and Macnab
      criteria score of the 2 groups. The mean follow-up period was 14 months. RESULTS:
      The average cannula introduction time (16.50 +/- 3.29 minutes) and the radiation
      exposure time (40.71 +/- 6.23 seconds) in the ZESSYS group were significantly
      reduced compared with the TESSYS group (cannula introduction time, 20.06 +/- 3.37
      minutes, P = 0.000; radiation exposure time, 49.20 +/- 7.84 seconds, P = 0.000).
      Intraoperative pain feeling score in the ZESSYS group was significantly improved
      compared with the TESSYS group (P = 0.021). There were no significant differences
      between the 2 groups for decompression time (P = 0.617), Macnab criteria (P =
      0.769), or visual analog scale and Oswestry Disability Index scores at the same
      time point (P > 0.05). No serious complication was observed in any patients in
      either group. CONCLUSIONS: The novel targeted foraminoplasty technique with the
      specially designed double-cannulas is an effective and safe treatment for lumbar
      intervertebral disc herniation. It reduces the difficulty of PELD learning,
      minimizes radiation exposure, and decreases intraoperative pain associated with
      foraminoplasty.

PMID- 29660554
TI  - Effect of Early Brain Infarction After Subarachnoid Hemorrhage: A Systematic
      Review and Meta-Analysis.
AB  - OBJECTIVE: Aneurysmal subarachnoid hemorrhage (aSAH) is an acute cerebrovascular
      event that leads to devastating consequences. Early brain infarction (EBI)
      develops very early, within the first 72 hours after bleeding, and may have a
      significant impact on long-term outcomes. The incidence and impact of EBI in the
      prognosis of aSAH remain uncertain. We performed a systematic review and meta
      analysis to evaluate the incidence of EBI in patients with aSAH and determine its
      effect on mortality and functional outcomes. METHODS: We performed a systematic
      review and meta-analysis. Inclusion criteria were 1) studies that evaluated aSAH
      within 72 hours after bleeding; 2) performed a brain imaging study up to 72 hours
      of hemorrhage; 3) used computed tomography or magnetic resonance imaging; and 4)
      included a description of the findings of the brain imaging study (whether or not
      an infarct was present). RESULTS: Ten studies that met the criteria were
      included. The incidence of EBI was 17%. The risk ratio for 3-month mortality was
      2.18 (95% confidence interval 1.48-3.30). The overall risk ratio for poor outcome
      was 2.26 (95% confidence interval 1.75-2.93). CONCLUSIONS: EBI plays an important
      role in the outcome of patients with aSAH. Its significant impact could represent
      a new therapeutic frontier for improving outcomes of these patients.

PMID- 29660555
TI  - Rare Hereditary Abnormal Bone Hyperplasia and Ossification of the Yellow Ligament
      Complicated by Thoracic Spinal Stenosis.
AB  - We report a rare case of familial inherited abnormal bone hyperplasia and
      ossification of the yellow ligament complicated by spinal stenosis. Complete
      reconstruction of stability and spinal cord decompression were achieved by
      posterior total laminectomy, fusion, and internal fixation. We cannot clearly
      describe the inheritance characteristics of the disease. Although the risk of
      surgical treatment is high, it is still necessary to perform surgery, and the
      effect of the operation is substantial.

PMID- 29660556
TI  - Comparative analysis of Ancylostoma ceylanicum mitochondrial genome with other
      Ancylostoma species.
AB  - Ancylostoma ceylanicum may inhabit the small intestine of canids, felids and
      humans, can pose a potential risk to public health. This study is the first time
      to amplify complete mitochondrial genome sequence of A. ceylanicum from dog and
      to compare it with Ancylostoma tubaeforme, Ancylostoma duodenale and Ancylostoma
      caninum. The results showed that the complete mitochondrial genome of A.
      ceylanicum was 13,660 bp in length, including 12 protein-coding genes, 2 rRNA
      genes and 22 tRNA genes and 3 non-coding regions (AT-rich region, SNCR and LNCR).
      Its mtDNA was the shortest, biased toward A and T at base composition, and higher
      than other three Ancylostoma species at total AT content. Its nad5 and nad6 genes
      used TTG and ATT as initiation codons, while other three Ancylostoma species used
      ATT and GTG or ATG. The 22 tRNA genes were different in length among four
      Ancylostoma species, but their anticodons were the same. Among 12 protein-coding
      genes, the cox1 gene was the lowest at AT content and minimum at Ka/Ks while the
      nad2 gene was the opposite. The phylogenetic tree showed that in the lineage of
      Ancylostoma, A. ceylanicum occurred on a branch external to other three
      Ancylostoma species, and A. caninum and A. tubaeforme had closer phylogenetic
      relationship than A. duodenale. This study not only enhances the mitochondrial
      genome database of Ancylostomatidae nematodes, but also provides new data for
      further phylogenetic studies among Ancylostomatidae nematodes.

PMID- 29660557
TI  - Theileria lestoquardi in Sudan is highly diverse and genetically distinct from
      that in Oman.
AB  - Malignant ovine theileriosis is a severe tick-borne protozoan disease of sheep
      and other small ruminants which is widespread in sub-Saharan Africa and the
      Middle East. The disease is of considerable economic importance in Sudan as the
      export of livestock provides a major contribution to the gross domestic product
      of this country. Molecular surveys have demonstrated a high prevalence of sub
      clinical infections of Theileria lestoquardi, the causative agent, among small
      ruminants. No information is currently available on the extent of genetic
      diversity and genetic exchange among parasites in different areas of the country.
      The present study used a panel of T. lestoquardi specific micro- and mini
      satellite genetic markers to assess diversity of parasites in Sudan (Africa) and
      compared it to that of the parasite population in Oman (Asia). A moderate level
      of genetic diversity was observed among parasites in Sudan, similar to that
      previously documented among parasites in Oman. However, a higher level of mixed
      genotype infection was identified in Sudanese animals compared to Omani animals,
      consistent with a higher rate of tick transmission. In addition, the T.
      lestoquardi genotypes detected in these two countries form genetically distinct
      groups. The results of this work highlight the need for analysis of T.
      lestoquardi populations in other endemic areas in the region to inform on novel
      approaches for controlling malignant theileriosis.

PMID- 29660558
TI  - Multilocus sequence analysis of Borrelia burgdorferi sensu lato isolates from
      Western Siberia, Russia and Northern Mongolia.
AB  - Lyme borreliosis (LB) is the most frequently recorded tick-transmitted disease in
      Eurasia. Tomsk Province, Western Siberia in Russia and Selenge Aimag in Northern
      Mongolia are leading regions in the LB incidence rate in these countries.
      Spirochaetes of the Borrelia burgdorferi sensu lato (s.l.) complex isolated from
      Ixodes ticks from Tomsk Province (n = 56) and Ixodes persulcatus ticks from
      Selenge Aimag (n = 5) were genetically characterized using Multi Locus Sequence
      Typing (MLST), analysis of the 5S23S rRNA intergenic spacer (IGS) amplicons, and
      p83/100 gene sequencing. According to MLST, B. afzelii (n = 26), B. bavariensis
      (n = 23), B. garinii (n = 11), and B. valaisiana (n = 1) isolates were detected
      in Tomsk Province, while B. afzelii and B. bavariensis isolates were identified
      in Selenge Aimag. Of the 32 revealed sequence types (ST), 21 STs were new and 14
      of the new STs belonged to B. afzelii. Several STs of B. afzelii, B. garinii and
      B. valaisiana identified in this study clustered with European STs found in I.
      ricinus ticks. Analysis of the 5S23S IGS demonstrated that the studied Borrelia
      strains showed RFLP pattern characteristic for the following 5S23S IGS types:
      VS461 (B. afselii), NT29 (B. bavariensis), 20047 (B. bavariensis and B. garinii),
      VS116 (B. valaisiana), and three new groups (B. afzelii and B. bavariensis).
      Notably, this is the first report of Asian B. bavariensis possessing a 5S23S IGS
      RFLP pattern identical to 20047, and analysis of the 5S23S IGS did not provide
      correct determination of Borrelia species occurring in Asia. Genotyping of
      Borrelia strains using the clpA, pepX, and p83/100 genes demonstrated the same
      result as genotyping based on MLST; and further investigations are required to
      confirm that these three genetic loci could be used for determination of
      bacterial species from the B. burgdorferi s.l. complex because data based on
      single loci may be misleading.

PMID- 29660559
TI  - Potassium dynamics and seizures: Why is potassium ictogenic?
AB  - Potassium channels dysfunction and altered genes encoding for molecules involved
      in potassium homeostasis have been associated with human epilepsy. These
      observations are in agreement with a control role of extracellular potassium on
      neuronal excitability and seizure generation. Epileptiform activity, in turn,
      regulates potassium homeostasis through mechanisms that are still not well
      established. We review here how potassium-associated processes are regulated in
      the brain and examine the mechanisms that support the role of potassium in
      triggering epileptiform activities.

PMID- 29660560
TI  - Phloem physics: mechanisms, constraints, and perspectives.
AB  - Plants have evolved specialized vascular tissues for the distribution of energy,
      water, nutrients, and for communication. The phloem transports sugars from
      photosynthetic source regions (e.g. mature leaves) to sugar sinks (e.g.
      developing tissues such as buds, flowers, roots). Moreover, chemical signals such
      as hormones, RNAs and proteins also move in the phloem. Basic physical processes
      strongly limit phloem anatomy and function. This paper provides an overview of
      recent research and perspectives on phloem biomechanics and the physical
      constraints relevant to sugar transport in plants.

PMID- 29660561
TI  - Cycling injury risk in London: A case-control study exploring the impact of cycle
      volumes, motor vehicle volumes, and road characteristics including speed limits.
AB  - Cycling injury risk is an important topic, but few studies explore cycling risk
      in relation to exposure. This is largely because of a lack of exposure data, in
      other words how much cycling is done at different locations. This paper helps to
      fill this gap. It reports a case-control study of cycling injuries in London in
      2013-2014, using modelled cyclist flow data alongside datasets covering some
      characteristics of the London route network. A multilevel binary logistic
      regression model is used to investigate factors associated with injury risk,
      comparing injury sites with control sites selected using the modelled flow data.
      Findings provide support for 'safety in numbers': for each increase of a natural
      logarithmic unit (2.71828) in cycling flows, an 18% decrease in injury odds was
      found. Conversely, increased motor traffic volume is associated with higher odds
      of cycling injury, with one logarithmic unit increase associated with a 31%
      increase in injury odds. Twenty-mile per hour compared with 30mph speed limits
      were associated with 21% lower injury odds. Residential streets were associated
      with reduced injury odds, and junctions with substantially higher injury odds.
      Bus lanes do not affect injury odds once other factors are controlled for. These
      data suggest that speed limits of 20 mph may reduce cycling injury risk, as may
      motor traffic reduction. Further, building cycle routes that generate new cycle
      trips should generate 'safety in numbers' benefits.

PMID- 29660562
TI  - Hebecarposides A-K, antiproliferative lanostane-type triterpene glycosides from
      the leaves of Lyonia ovalifolia var. hebecarpa.
AB  - Eleven previously undescribed lanostane-type triterpene glycosides,
      hebecarposides A-K, were isolated from the leaves of Lyonia ovalifolia var.
      hebecarpa (Ericaceae), along with two known analogues, lyonifolosides L and O.
      The structures of hebecarposides A-K were established by extensive spectroscopic
      analysis and chemical methods, and the absolute configuration of C-24 in
      hebecarposides A and E was determined to be S and R, respectively, by a Mo2(OAc)4
      induced electronic circular dichroism method. This is the first report of the
      presence of lanostane-type triterpene glycosides in L. ovalifolia var. hebecarpa.
      All compounds were evaluated for their antiproliferative activities against five
      cancer cell lines, SMMC-7721, HL-60, SW480, MCF-7, and A-549, and a normal
      epithelial cell line BEAS-2B, and none of them showed general cytotoxity to the
      normal cell line BEAS-2B. Interestingly, hebecarposides C, D, G, and K
      selectively inhibited the proliferation of HL-60 and SMMC-7721 cell lines, and
      hebecarposides C and D showed significant anti-proliferative activities against A
      549 cell lines than the positive control, cis-platin. In addition, hebecarposides
      C and H exhibited more potent anti-proliferative activities against MCF-7 than
      cis-platin.

PMID- 29660564
TI  - Closing the gap: A whole of school approach to Aboriginal and Torres Strait
      Islander inclusivity in higher education.
AB  - The recruitment and retention of Aboriginal and Torres Strait Islander nurses and
      midwives is key to the delivery of culturally appropriate health care and
      improving the health outcomes of Aboriginal and Torres Strait Islander people. A
      working group to address inclusion and engagement of Aboriginal and Torres Strait
      Islander students at a West Australian University has impacted on the curricula,
      faculty staff and Aboriginal and Torres Strait Islander students within the
      School of Nursing and Midwifery. The University's Reconciliation Action Plan was
      the foundation and catalysed the group to promote cultural safety education for
      staff and provide inclusive activities for Aboriginal and Torres Strait Islander
      students. A conceptual framework was developed to demonstrate the action taken
      within the School of Nursing and Midwifery to address the inequity for Aboriginal
      and Torres Strait Islander students that could be seen to exist. Through
      collaboration with staff and students, both Aboriginal and Torres Strait Islander
      people and non-Aboriginal people, a shared understanding and goal setting has
      developed to enable positive action to provide ongoing support for these students
      at all parts of their journey in higher education. This paper will highlight the
      process involved to promote the recruitment, retention and academic success of
      these students.

PMID- 29660563
TI  - Exploring the functional nature of synaesthetic colour: Dissociations from colour
      perception and imagery.
AB  - Individuals with grapheme-colour synaesthesia experience anomalous colours when
      reading achromatic text. These unusual experiences have been said to resemble
      'normal' colour perception or colour imagery, but studying the nature of
      synaesthesia remains difficult. In the present study, we report novel evidence
      that synaesthetic colour impacts conscious vision in a way that is different from
      both colour perception and imagery. Presenting 'normal' colour prior to binocular
      rivalry induces a location-dependent suppressive bias reflecting local
      habituation. By contrast, a grapheme that evokes synaesthetic colour induces a
      facilitatory bias reflecting priming that is not constrained to the inducing
      grapheme's location. This priming does not occur in non-synaesthetes and does not
      result from response bias. It is sensitive to diversion of visual attention away
      from the grapheme, but resistant to sensory perturbation, reflecting a reliance
      on cognitive rather than sensory mechanisms. Whereas colour imagery in non
      synaesthetes causes local priming that relies on the locus of imagined colour,
      imagery in synaesthetes caused global priming not dependent on the locus of
      imagery. These data suggest a unique psychophysical profile of high-level colour
      processing in synaesthetes. Our novel findings and method will be critical to
      testing theories of synaesthesia and visual awareness.

PMID- 29660565
TI  - Undergraduate student nurses' attitudes towards using social media websites: A
      study from Jordan.
AB  - BACKGROUND: The use of social media by university students is recognized
      worldwide. Student nurses are no exception, yet no studies have been reported to
      investigate the nurse students' use and views of social media in Jordan. The
      current study aims to assess the validity and reliability of an Arabic version of
      the modified Students Nurses' Use and Views of Social Media survey. METHODS: In a
      cross-sectional study conducted on 395 student nurses aged 19-39 enrolled at two
      universities (one public and one private) in north Jordan, information on their
      use and attitude to social media was obtained using the Arabic version of the
      Students Nurses' Use and Views of Social Media survey. Exploratory factor
      analysis and correlation matrices were conducted to assess the validity and
      reliability of the tool. RESULTS: The Arabic version of the tool had a 0.84 alpha
      of internal consistency indicating a high level of reliability. The scale showed
      multi-dimensionality with items loading on two factors. CONCLUSION: The Arabic
      version of the Students Nurses' Use and Views of Social Media questionnaire
      demonstrated initial reliability and validity. This study reports positive
      attitudes of Jordanian student nurses towards professional and academic use of
      social media.

PMID- 29660566
TI  - Extrapleural solitary fibrous tumor: A distinct entity from pleural solitary
      fibrous tumor. An update on clinical, molecular and diagnostic features.
AB  - Solitary fibrous tumor (SFT) is a mesenchymal neoplasm that was originally
      described to be localized in the pleura, but thereafter, this has been reported
      in several anatomic sites. Although the etiology of the neoplasm remains largely
      unknown, the pathogenesis seems to be related to an NAB2-STAT6 fusion gene due to
      paracentric inversion on chromosome 12q13. The diagnosis of extrapleural SFT is
      challenging, owing to its rarity, and requires an integrated approach that
      includes specific clinical, histological, immunohistochemical, and even molecular
      findings. Histologically, extrapleural SFT shares morphological features same as
      those of the pleural SFT because it is characterized by a patternless
      distribution of both oval- and spindle-shaped cells in a variable collagen
      stroma. In addition, morphological variants of mixoid, fat-forming, and giant
      cell-rich tumors are described. A correct diagnosis is mandatory for a proper
      therapy and management of the patients with extrapleural SFT, as extrapleural SFT
      is usually more aggressive than pleural form, particularly cases occurring in the
      mediastinum, retroperitoneum, pelvis, and meninges. Although SFT is usually
      considered as a clinically indolent neoplasm, the prognosis is substantially
      unpredictable and only partially related to morphological features. In this
      context, cellularity, neoplastic borders, cellular atypias, and mitotic activity
      can show a wide range of variability. We review extrapleural SFT by discussing
      diagnostic clues, differential diagnosis, recent molecular findings, and
      prognostic factors.

PMID- 29660567
TI  - Summary of expression of SPARC protein in cutaneous vascular neoplasms and
      mimickers.
AB  - BACKGROUND: Serum protein acidic and rich in cysteine (SPARC) is a matricellular
      glycoprotein, which regulates cell proliferation and facilitates intracellular
      transport of albumin bound particles including chemotherapeutic agents such as
      Nab-paclitaxel/ABI-007. Therefore the presence of SPARC may achieve higher intra
      tumoral drug concentration with lower dosage and thus reduce systemic side
      effects. Several trials of ABI-007, in melanoma, show promising clinical
      activity. DESIGN: Fifty-four cases of dermal based neoplasms were retrieved
      including 24 angiosarcomas (AS), 10 hemangiomas, 9 nodular melanomas, 4 Kaposi
      sarcomas (KS), 3 leiomyosarcomas (LMS), 3 atypical fibroxanthomas (AFX) and 1
      spindle cell squamous cell carcinoma (SSCC). SPARC immunohistochemistry (IHC) was
      performed with a mouse monoclonal antibody. RESULTS: SPARC expression was
      detected in a majority of AS (17/24), melanomas (8/9), AFX (3/3), LMS (3/3) and
      KS (4/4) with some expression in hemangiomas (3/10), while being negative in SSCC
      (0/1); and was significantly associated with tumor group (p = 0.017). Although a
      significant difference in overall survival was observed between SPARC expression
      groups (positive vs. negative) for all patients, there was no significant
      difference noted among angiosarcoma patients. CONCLUSION: We have confirmed the
      presence of SPARC expression in melanoma, KS, LMS and AS and also detected it for
      the first time in AFX. Since paclitaxel has shown some effectiveness in AS,
      melanoma and KS, ABI-007 could also be beneficial in these patients.

PMID- 29660568
TI  - Interdigitating dendritic cell sarcoma: Clinicopathologic study of 8 cases with
      review of the literature.
AB  - To investigate the clinicopathologic features and differential diagnoses of
      interdigitating dendritic cell sarcoma (IDCS), the clinical, morphological and
      immunohistochemical features of eight cases of IDCS were collected and analyzed.
      Three patients were males and five were females, the mean age and the median age
      were 56.5 years and 57 years respectively. Clinically, the majority of cases
      involved lymph nodes. Microscopically, neoplastic cells were spindle or ovoid,
      forming fascicles or whorls. Every case had active mitosis figures.
      Immunohistochemically, these neoplastic cells were consistently positive for
      S100, but negative for CD21 and specific B-cell and T-cell associated antigens.
      Follow-up results were available in 7 cases, of which 5 cases of localized
      lesions survived, 2 cases died of organ involvement. Interdigitating dendritic
      cell sarcoma is an extremely rare neoplasm, with inferior prognosis and without
      standard treatment regimen. IDCS has similar but unique clinicopathologic
      features and the differential diagnoses include other histiocytic and dendritic
      cell neoplasms and malignant melanoma.

PMID- 29660569
TI  - Analytical insight into "breathing" crack-induced acoustic nonlinearity with an
      application to quantitative evaluation of contact cracks.
AB  - To characterize fatigue cracks, in the undersized stage in particular, preferably
      in a quantitative and precise manner, a two-dimensional (2D) analytical model is
      developed for interpreting the modulation mechanism of a "breathing" crack on
      guided ultrasonic waves (GUWs). In conjunction with a modal decomposition method
      and a variational principle-based algorithm, the model is capable of analytically
      depicting the propagating and evanescent waves induced owing to the interaction
      of probing GUWs with a "breathing" crack, and further extracting linear and
      nonlinear wave features (e.g., reflection, transmission, mode conversion and
      contact acoustic nonlinearity (CAN)). With the model, a quantitative correlation
      between CAN embodied in acquired GUWs and crack parameters (e.g., location and
      severity) is obtained, whereby a set of damage indices is proposed via which the
      severity of the crack can be evaluated quantitatively. The evaluation, in
      principle, does not entail a benchmarking process against baseline signals. As
      validation, the results obtained from the analytical model are compared with
      those from finite element simulation, showing good consistency. This has
      demonstrated accuracy of the developed analytical model in interpreting contact
      crack-induced CAN, and spotlighted its application to quantitative evaluation of
      fatigue damage.

PMID- 29660571
TI  - Emotional intelligence in patients with posttraumatic stress disorder, borderline
      personality disorder and healthy controls.
AB  - Emotional intelligence as a part of social cognition has, to our knowledge, never
      been investigated in patients with Posttraumatic Stress Disorder (PTSD), though
      the disorder is characterized by aspects of emotional dysfunctioning. PTSD often
      occurs with Borderline Personality Disorder (BPD) as a common comorbidity.
      Studies about social cognition and emotional intelligence in patients with BPD
      propose aberrant social cognition, but produced inconsistent results regarding
      emotional intelligence. The present study aims to assess emotional intelligence
      in patients with PTSD without comorbid BPD, PTSD with comorbid BPD, and BPD
      patients without comorbid PTSD, as well as in healthy controls. 71 patients with
      PTSD (41 patients with PTSD without comorbid BPD, 30 patients with PTSD with
      comorbid BPD), 56 patients with BPD without PTSD, and 63 healthy controls filled
      in the Test of Emotional Intelligence (TEMINT). Patients with PTSD without
      comorbid BPD showed impairments in emotional intelligence compared to patients
      with BPD without PTSD, and compared to healthy controls. These impairments were
      not restricted to specific emotions. Patients with BPD did not differ
      significantly from healthy controls. This study provides evidence for an impaired
      emotional intelligence in PTSD without comorbid BPD compared to BPD and healthy
      controls, affecting a wide range of emotions.

PMID- 29660570
TI  - The tangled roots of inner speech, voices and delusions.
AB  - The role of inner speech in the experience of auditory verbal hallucinations
      (AVH) and delusions remains unclear. This exploratory study tested for
      differences in inner speech (assessed via self-report questionnaire) between 89
      participants with psychosis and 37 non-clinical controls. We also tested for
      associations of inner speech with, i) state/trait AVH, ii) AVH-severity; iii)
      patients' relations with their voices, and; iv) delusion-severity. Persons with
      psychosis had greater levels of dialogic inner speech, other people in inner
      speech, and evaluative/motivational inner speech than non-clinical controls.
      Those with state, but not trait AVH had greater levels of dialogic and
      evaluative/motivational inner speech than non-clinical controls. After
      controlling for delusions, there was a positive relation between AVH-severity and
      both evaluative/motivational inner speech and other people in inner speech.
      Participants with greater levels of dialogic inner speech reported better
      relations both with and between their voices. There was no association between
      delusion-severity and inner speech. These results highlight the importance of
      better understanding relations between inner speech and AVH, provide avenues for
      future research, and underscore the need for research into the interrelatedness
      of inner speech, voices and delusions, and the complexities involved in
      disentangling these experiences.

PMID- 29660572
TI  - Differential relationship of jumping-to-conclusions and incorrigibility with
      delusion severity.
AB  - Reasoning biases such as jumping-to-conclusions (JTC) and incorrigibility have
      been suggested to contribute to the generation and maintenance of delusions.
      However, it is still debated whether these biases represent stable traits of
      patients with delusions, or are related to state fluctuations of delusion
      severity. The present study aimed to elucidate this question by combining a cross
      sectional with a longitudinal approach. JTC, incorrigibility and delusion
      severity were assessed in 79 patients with a history of delusions over a 6-month
      period. To allow for a differentiated look into effects of time vs. symptom
      changes, patients were divided into patients with (D+) and without (D-) current
      delusions at baseline. Significant improvement of delusions was noted in D+ at
      follow-up. JTC did not differ between the two patient groups either at baseline
      or over time. In contrast, incorrigibility was significantly higher in D+ than D-
      at baseline; this difference remained stable throughout the 6-month follow-up
      period. The two biases did not significantly co-vary over time. Our results
      suggest a dissociation between incorrigibility and JTC as regards their relation
      to current presence of delusions, and tentatively support theoretical accounts
      attributing different roles to the two biases in the generation (JTC) and
      maintenance (incorrigibility) of delusions.

PMID- 29660573
TI  - Midwifery in Iceland: From vocational training to university education.
AB  - Midwifery education is a foundation for health professionals' competence in
      providing quality healthcare for the benefit of women, their families and
      society. This paper describes midwifery and the development of midwifery
      education in Iceland. It examines policy and extensive reforms, from hospital
      based vocational training in midwifery to an academic university education, and
      the impact on the scope of midwifery practice in Iceland. The university-based
      programme, with its emphasis on autonomy of the midwife, seems to have affected
      the context of home birth and strengthened midwives' role in primary healthcare.
      Education reform with a focus on evidence-based practice and midwife-led
      continuity of care has had limited influence within the hospital system, where
      the structure of care is fragmented and childbirth is under threat of increasing
      interventions. Research is needed on the role of education in supporting evidence
      based practice, normal childbirth and reproductive health in the Icelandic
      context.

PMID- 29660574
TI  - The effectiveness of learning portfolios in learning participation and learners'
      perceptions of skills and confidence in the mother of preterm infant.
AB  - OBJECTIVE: The purpose of this study was to investigate the effectiveness of
      preterm infant learning portfolios in enabling mothers to develop infant care
      knowledge and skills, as well as confidence in their abilities. DESIGN: This
      study used a quasi-experimental design. SETTING AND PARTICIPANTS: The sample
      consisted of 52 mothers with preterm infants recruited at a neonatal intermediate
      unit of a medical centre in central Taiwan. Among those, 26 participants in the
      control group received regular health education and 26 participants in the
      experimental group received learning portfolios and regular care. INTERVENTION:
      The Preterm Infant Care Learning Portfolio (PICLP) is a semi-structured learning
      portfolio which was provided by nurses. Intervention started with 15 min of
      instructions on how to use PICLP, including a list of learning task and methods
      of self-assessment. Follow-up sessions of 5-10 min were conducted after each
      learning task. The frequency of learning skills could be adjusted depending on
      participants' learning needs. MEASUREMENTS: Self-administered questionnaires
      regarding knowledge of and skills in preterm infant care and maternal confidence
      were used to evaluate the effectiveness of the intervention; the questionnaires
      were conducted before the intervention, 1 day before discharge and 1 month after
      discharge. We also tracked the frequency with which participants attended
      instructional sessions before discharged. FINDINGS: Mothers' preterm infant care
      knowledge and skills and confidence improved in both groups after the
      intervention. The experimental group showed greater improvement than the control
      group by post-test 2; there was no statistical difference between groups at 1 day
      before discharge and 1 month after discharge. However, participants in the
      experimental group came for instructional sessions on baby care for more
      frequently than the control group. The frequency of learning sessions attended
      was a predictor of improved scores of the skill assessment before discharge.
      CONCLUSIONS: Both programmes led to improvements in preterm infant care knowledge
      and skills and maternal confidence. Giving mothers learning portfolios appears to
      stimulate significantly greater participation in hospital-based instructional
      programmes, which should in turn lead to greater long-term retention of learning.
      The learning portfolios may have an additional benefit in promoting acquisition
      of care abilities for mothers with preterm infant before hospital discharge and
      application of these abilities at home. IMPLICATION FOR PRACTICE: At-home care
      for preterm infants requires specialized care skills and confidence. Learning
      portfolios can be used as an effective learner-centred strategy for teaching
      these health care abilities.

PMID- 29660575
TI  - Development and implementation of a competency-based clinical evaluation tool for
      midwifery education.
AB  - BACKGROUND: The learning goals and evaluation strategies of competency-based
      midwifery programs must be explicit and well-defined. In the US, didactic
      learning is evaluated through a standardized certification examination, but
      standardized clinical competence evaluation is lacking. DESCRIPTION OF THE TOOL:
      The Midwifery Competency Assessment Tool (MCAT) has been adapted from the
      International Confederation of Midwives' (ICM) "Essential Competencies" and from
      the American College of Nurse-Midwives' (ACNM) "Core Competencies", with student
      self-evaluation based on Benner's Novice-to-Expert theory. The MCAT allows for
      the measurement and monitoring of competence development in all domains of full
      scope practice over the course of the midwifery program. APPLICATION AND
      EVALUATION OF THE TOOL: Strengths of the MCAT are that it provides clear learning
      goals and performance evaluations for students, ensures and communicates content
      mapping across a curriculum, and highlights strengths and gaps in clinical
      opportunities at individual clinical sites and for entire programs. Challenges of
      the MCAT lie in balancing the number of competency items to be measured with the
      tedium of form completion, in ensuring the accuracy of student self-evaluation,
      and in determining "adequate" competence achievement when particular clinical
      opportunities are limited. CONCLUSIONS: Use of the MCAT with competency-based
      clinical education may facilitate a more standardized approach to clinical
      evaluation, as well as a more strategic approach to clinical site development and
      use.

PMID- 29660576
TI  - Built spaces and features associated with user satisfaction in maternity waiting
      homes in Malawi.
AB  - OBJECTIVE: To assess satisfaction with maternity waiting home built spaces and
      features in women who are at risk for underutilizing maternity waiting homes
      (i.e. residential facilities that temporarily house near-term pregnant mothers
      close to healthcare facilities that provide obstetrical care). Specifically we
      wanted to answer the questions: (1) Are built spaces and features associated with
      maternity waiting home user satisfaction? (2) Can built spaces and features
      designed to improve hygiene, comfort, privacy and function improve maternity
      waiting home user satisfaction? And (3) Which built spaces and features are most
      important for maternity waiting home user satisfaction? DESIGN: A cross-sectional
      study comparing satisfaction with standard and non-standard maternity waiting
      home designs. Between December 2016 and February 2017 we surveyed expectant
      mothers at two maternity waiting homes that differed in their design of built
      spaces and features. We used bivariate analyses to assess if built spaces and
      features were associated with satisfaction. We compared ratings of built spaces
      and features between the two maternity waiting homes using chi-squares and t
      tests to assess if design features to improve hygiene, comfort, privacy and
      function were associated with higher satisfaction. We used exploratory robust
      regression analysis to examine the relationship between built spaces and features
      and maternity waiting home satisfaction. SETTING: Two maternity waiting homes in
      Malawi, one that incorporated non-standardized design features to improve
      hygiene, comfort, privacy, and function (Kasungu maternity waiting home) and the
      other that had a standard maternity waiting home design (Dowa maternity waiting
      home). PARTICIPANTS: 322 expectant mothers at risk for underutilizing maternity
      waiting homes (i.e. first-time mothers and those with no pregnancy risk factors)
      who had stayed at the Kasungu or Dowa maternity waiting homes. FINDINGS: There
      were significant differences in ratings of built spaces and features between the
      two differently designed maternity waiting homes, with the non-standard design
      having higher ratings for: adequacy of toilets, and ratings of heating/cooling,
      air and water quality, sanitation, toilets/showers and kitchen facilities,
      building maintenance, sleep area, private storage space, comfort level, outdoor
      spaces and overall satisfaction (p = <.0001 for all). The final regression model
      showed that built spaces and features that are most important for maternity
      waiting home user satisfaction are toilets/showers, guardian spaces, safety,
      building maintenance, sleep area and private storage space (R2 = 0.28). KEY
      CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: The design of maternity waiting home
      built spaces and features is associated with user satisfaction in women at risk
      for underutilizing maternity waiting homes, especially related to
      toilets/showers, guardian spaces, safety, building maintenance, sleep area and
      private storage space. Improving maternity waiting home built spaces and features
      may offer a promising area for improving maternity waiting home satisfaction and
      reducing barriers to maternity waiting home use.

PMID- 29660577
TI  - Value and best way for detection of Sentinel lymph node in early stage
      endometrial cancer: Selective lymphadenectomy algorithm.
AB  - INTRODUCTION: The cornerstone of treatment for endometrial carcinoma is total
      abdominal hysterectomy and bilateral salpingo-oophoprectomy. Pelvic
      lymphadenectomy, with or without para-aortic lymphadenectomy, plays an important
      role in the surgical staging of endometrial carcinoma, and provides more accurate
      prognostic information. AIMS: We aimed to evaluate the value and techniques for
      SLN mapping in early stage endometrial cancer with low risk for lymph node
      metastasis and whether selective or systematic lymphadenectomy is needed
      according to the results of proposed algorithm. METHOD: Between June 2016 and
      June 2017, 120 patients with early stage endometrial cancer with low risk for
      nodal metastasis underwent surgical staging. Patients were classified equally
      according to SLN mapping technique used for injecting the methylene blue dye.
      Group A included hysteroscopic guided methylene blue injection, Group B included
      transcervical injection, Group C included subserosal uterine injection and Group
      D included combined transcervical and subserosal injection. Blue lymph nodes and
      enlarged suspicious whether stained or non stained ones were dissected for frozen
      section evaluation done then bilateral pelvic node dissection was done and
      tissues were sent for pathological examination. RESULTS: Clinical and
      pathological SLN detection were more with hysteroscopic technique than others and
      pathological detection was lower than clinical detection in all techniques.
      Metastatic disease was more common in nodes with suspicious appearance. About 10%
      of negative suspicious and mapped nodes were associated with positive other nodes
      for metastasis. CONCLUSION: SLN in endometrial cancer has a role in staging of
      endometrial cancer with best technique for detection, hysteroscopic guided blue
      dye injection. SLN can be used in patients with low risk for lymph node
      metastasis for selective lymphadenectomy. Blue dye labelling using methylene blue
      dye is good in low resource countries as it is cheap. We recommended the
      following algorithm for surgical staging in early endometrial cancer with better
      results than using SLN alone. Stage I type 1, grade 1,2 endometrial cancer should
      undergo surgical staging with initial evaluation of the peritoneum which if
      affected, it is stage III with no need for lymphadenectomy. Then, dissection of
      the blue and suspicious nodes which if any is positive on frozen section,
      selective same side pelvic and paraaortic nodal dissection should be done. If
      they are negative, no need for lymphadenectomy. This approach can help patients
      to avoid the side effects associated with a complete lymphadenectomy. The higher
      rate of detection using this algorithm is related to combining the suspicions
      nodes with the stained ones.

PMID- 29660578
TI  - Implementing the Risk of Endometrial Malignancy Algorithm (REM) adding obesity as
      a predictive factor: Results of REM-B in a single-center survey.
AB  - OBJECTIVE: In 2013, our group assessed a risk stratification tool of endometrial
      cancer (EC), called REM (Risk of Endometrial Malignancy). A well known risk
      factor for EC is body mass index (BMI). In fact, (BMI > 30 and <35 kg/m2) and
      severe obesity (BMI > 35 kg/m2) were associated with a 2.6-fold and a 4.7-fold
      increase in EC risk, respectively. Therefore, in the present study we aim to
      improve the performance of REM, including BMI and developing a new scoring
      system, called REM-B (Risk of Endometrial Malignancy score associated to BMI), to
      classify patients into high risk or low risk groups for EC. STUDY DESIGN: Women,
      between 45 and 80 years, diagnosed with ultrasound endometrial abnormalities and
      scheduled to have surgery were enrolled on a prospective study at Department of
      Gynaecologic Oncology of Campus Bio-Medico of Rome. Preoperative clinical,
      ultrasound and laboratory features were taken into account. RESULTS: A total of
      675 patients (88 with EC and 587 with benign endometrial disease) were divided in
      training set (TS) and verification set (VS). Age, symptom, BMI, HE4 levels and
      ultrasound endometrial thickness were found statistically significant and
      included into multivariate logistic regression model in order to determine the
      probability to have EC. REM-B showed an overall sensitivity of 94.7% (versus 92%
      of REM) and a specificity of 97.4% (versus 96% of REM). CONCLUSIONS: Our data
      support the use of REM-B to triage patients into low and high risk of EC, even if
      an external validation of model is needed.

PMID- 29660579
TI  - The effect of dermal benzophenone-2 administration on immune system activity,
      hypothalamic-pituitary-thyroid axis activity and hematological parameters in male
      Wistar rats.
AB  - Benzophenones used as UV filters, in addition to the effects on the skin, can be
      absorbed into the blood and affect the function of certain organs. So far, their
      effects on the sex hormone receptors and gonadal function have been studied, but
      not much is known about their potential action on other systems. The aim of the
      present study was to determine the effect of benzophenone-2 (BP-2) on immune
      system activity, hypothalamic-pituitary-thyroid (HPT) axis activity and
      hematological parameters. BP-2 was administered dermally, twice daily at a dose
      of 100 mg/kg for 4-weeks to male Wistar rats. Immunological and hematological
      parameters and HPT axis activity were assayed 24 h after the last administration.
      It was found that BP-2 did not change relative weights of the thymus and spleen
      and did not exert toxic effect on tymocytes and splenocytes. However, this
      compound increased proliferative activity of splenocytes, enhanced metabolic
      activity of splenocytes and thymocytes and nitric oxide production of these
      cells. In animals exposed to BP-2, the HPT axis activity was increased, as
      evidenced by reduction in the thyroid stimulating hormone (TRH) level and
      increase in free fraction of triiodothyronine (fT3) and thyroxin (fT4) in blood.
      BP-2 had no effect on leukocyte, erythrocyte and platelet counts or on morphology
      and hemoglobin content in erythrocytes. The conducted research showed that
      dermal, sub-chronic BP-2 administration evoked hyperthyroidism, increased
      activity or function of the immune cells but did not affect hematological
      parameters. We suggest that topical administration of BP-2 leading to a prolonged
      elevated BP-2 level in blood causes hyperthyroidism, which in turn may be
      responsible for the increased immune cell activity or function. However, only
      future research can explain the mechanism and functional importance of the
      changes in thyroid hormones and immunological parameters observed after exposure
      to BP-2.

PMID- 29660580
TI  - An evaluation of kurtosis beamforming in magnetoencephalography to localize the
      epileptogenic zone in drug resistant epilepsy patients.
AB  - OBJECTIVE: Kurtosis beamforming is a useful technique for analysing
      magnetoencephalograpy (MEG) data containing epileptic spikes. However, the
      implementation varies and few studies measure concordance with subsequently
      resected areas. We evaluated kurtosis beamforming as a means of localizing spikes
      in drug-resistant epilepsy patients. METHODS: We retrospectively applied kurtosis
      beamforming to MEG recordings of 22 epilepsy patients that had previously been
      analysed using equivalent current dipole (ECD) fitting. Virtual electrodes were
      placed in the kurtosis volumetric peaks and visually inspected to select a
      candidate source. The candidate sources were compared to the ECD localizations
      and resection areas. RESULTS: The kurtosis beamformer produced interpretable
      localizations in 18/22 patients, of which the candidate source coincided with the
      resection lobe in 9/13 seizure-free patients and in 3/5 patients with persistent
      seizures. The sublobar accuracy of the kurtosis beamformer with respect to the
      resection zone was higher than ECD (56% and 50%, respectively), however, ECD
      resulted in a higher lobar accuracy (75%, 67%). CONCLUSIONS: Kurtosis beamforming
      may provide additional value when spikes are not clearly discernible on the
      sensors and support ECD localizations when dipoles are scattered. SIGNIFICANCE:
      Kurtosis beamforming should be integrated with existing clinical protocols to
      assist in localizing the epileptogenic zone.

PMID- 29660581
TI  - Metal enhanced fluorescence (MEF) for biosensors: General approaches and a review
      of recent developments.
AB  - Fluorescence-based biosensor platforms have been intensively investigated not
      only to increase the sensitivity but also to improve the performance of
      biosensors. By exploiting metal from the macroscopic down to the nanoscopic
      surface, various architectures have been devised to manipulate fluorescence
      signals (enhancement, quenching) within near-optical fields. The interaction of a
      metallic surface with proximal fluorophores (in the range of 5-90 nm) has
      beneficial effects on optical properties such as an increased quantum yield,
      improved photostability and a reduced lifetime of fluorophores. This phenomenon
      called metal-enhanced fluorescence (MEF) has been extensively used in biosensory
      applications. However, their applications for biological analysis practically
      remain challenging in biological microenvironments. Therefore, this review
      primarily provides a general overview of MEF biosensor systems from the basic
      mechanism to state-of-the-art biological applications. The review also covers the
      pros and cons of MEF biosensor as well as discussions about further directions in
      biological perspectives.

PMID- 29660582
TI  - Highly stable and regenerative graphene-diamond hybrid electrochemical biosensor
      for fouling target dopamine detection.
AB  - Graphene is widely recognized as a promising nanomaterial for the construction of
      high-performance electrochemical biosensors. However, the lack of strong
      interfacial forces between graphene and conductive substrates is a bottleneck in
      the fabrication of highly stable graphene electrodes. In this work, few-layer
      graphene was directly formed on a high pressure high temperature (HPHT) diamond
      substrate via sp3-to-sp2 conversion by catalytic thermal treatment and using
      diamond itself as the carbon source. The hybrid electrode prototype was also
      highly conductive and had a linear electrochemical response to dopamine in the
      concentration range of 5 MUM - 2 mM, with a low detection limit of 200 nM. After
      prolonged and repeated exposure to dopamine, electrode fouling was observed which
      led to sensitivity degradation. Based on the strong interfacial bonding between
      graphene and HPHT diamond, regeneration of the fouled electrode and full
      performance recovery would be easily achieved by ultrasonic cleaning. The hybrid
      electrode is highly robust, and shows potential in its application to the
      detection of biofouling molecules, food processing and wastewater treatment.

PMID- 29660583
TI  - AIE-based superwettable microchips for evaporation and aggregation induced
      fluorescence enhancement biosensing.
AB  - Superwettable microchips with superhydrophilic microwells on superhydrophobic
      substrate have attracted increasing attention in fluorescence-based biological
      and medical diagnostics. However, traditional fluorophores often suffer from the
      aggregation-caused quenching (ACQ) problem at high concentration or in aggregated
      state. Here, we developed an AIE-based superwettable microchip by combining the
      evaporation-induced enrichment of superwettable microchips and the aggregation
      induced emission of AIEgens together into one chip. Benefitting from the
      synergistic effect of the above two mechanisms, the AIE molecules (TPE-Z, a
      tetraphenylethene salt) were enriched from the diluted solution via evaporation
      and aggregated within the superhydrophilic microwell and then realized the
      fluorescence enhancement. Based on the dual enhancement effect of the AIE-based
      superwettable microchip, microRNA-141 (miR-141) can be detected with excellent
      reproducibility, sensitivity and specificity. A low detection limit of 1 pM can
      be achieved with higher signal-to-noise ratio than the traditional fluorescent
      probes. The proposed AIE-based superwettable microchip will provide a simple
      fluorescence enhancement biosensing platform for rapid, multiplexed and high
      throughput analysis of specific targets in environmental monitoring, food safety,
      medical diagnosis and related research areas.

PMID- 29660584
TI  - Facile one-pot synthesis of visible light-responsive BiPO4/nitrogen doped
      graphene hydrogel for fabricating label-free photoelectrochemical tetracycline
      aptasensor.
AB  - It is fundamental to develop highly efficient visible light-responsive
      photoelectrochemical (PEC) performance material for fabricating PEC biosensor.
      Herein, BiPO4/three-dimensional nitrogen doped graphene hydrogel (3DNGH)
      nanocomposites were prepared for the first time via a facile one-pot hydrothermal
      route. In this nanoarchitecture, the BiPO4 nanorods were anchored onto the porous
      structure of 3DNGH. Compared with pristine BiPO4, the absorption of BiPO4/3DNGH
      has been extend to visible-light region, and the energy band gap of BiPO4/3DNGH
      was calculated to be 2.10 eV, which was greatly narrower than that of pristine
      BiPO4 with a band gap of 3.85 eV. Under visible light irradiation, the
      photocurrent signal of the as-prepared BiPO4/3DNGH was 847.2-fold, 4.1-fold and
      2.3-fold enhanced comparing to pristine BiPO4, BiPO4 functionalized reduced
      graphene oxide and BiPO4/nitrogen doped graphene. The enhancement of such
      photocurrent signal was attributed to the introduction of 3DNGH, which was
      capable to improve the charge transfer rate and also the efficiency of visible
      light utilization of BiPO4. Based on the excellent PEC properties of BiPO4/3DNGH,
      a label-free PEC aptasensor for selectivity and sensitivity detection of
      tetracycline (Tc) was successfully established by using Tc aptamer as a
      biorecognition element. Under optimized conditions, the proposed PEC aptasensor
      exhibited a wide linear in the range from 0.1 nmol L-1 to 1 MUmol L-1 as well as
      a low detection limit of 0.033 nmol L-1 (S/N = 3). The prepared BiPO4/3DNGH
      nanocomposites would serve as a promising visible light-responsive photoactive
      material for fabrication of PEC biosensors with high performance.

PMID- 29660585
TI  - Real-time quartz crystal microbalance cytosensor based on a signal recovery
      strategy for in-situ and continuous monitoring of multiple cell membrane
      glycoproteins.
AB  - A real-time quartz crystal microbalance (QCM) cytosensor based on a signal
      recovery strategy was first developed for in-situ and continuous monitoring of
      multiple cell membrane glycoproteins. In this work, gold nanoparticles (AuNPs)
      were linked with ligands to fabricate ligand-functionalized mass nanoprobes with
      signal amplification for increasing monitoring sensitivity. The mass nanoprobes
      bound to cell surface could be eluted with glycine-hydrochloric acid buffer,
      which led to a quick recovery of resonance frequency. Using the strategy, folate
      receptors (FR), CD44 molecule and epidermal growth factor receptor (EGFR) on cell
      membrane as the models were monitored continuously. The quantification result of
      MDA-MB-231 cells showed a range of linearity of 3.0 * 104 to 1.0 * 106 cells and
      a detection limit of 5.0 * 103 cells. Furthermore, the multianalyte cytosensor
      exhibited three sensitive and recoverable frequency shifts during continuous
      monitoring for in-situ and continuous evaluation of the expression levels of FR,
      CD44 and EGFR on cell membrane, which exhibited that the average numbers of
      molecules of FR, CD44 and EGFR per MDA-MB-231 cell were 0.5 * 106, 0.2 * 106 and
      1.4 * 105 with the relative standard deviation of 4.8%, 4.5% and 5.1%,
      respectively. Compared with monolithic multichannel QCM, the multianalyte
      cytosensor based on a single microbalance could not only exclude acoustic
      interference but also reduce instrumental cost. This work provided a simple and
      efficient QCM cytosensor for in-situ and continuous monitoring of multiple cell
      membrane glycoproteins that offered a new avenue for early diagnosis of cancer.

PMID- 29660586
TI  - Open external circuit for microbial fuel cell sensor to monitor the nitrate in
      aquatic environment.
AB  - This study employed an open external circuit, rather than a closed circuit
      applied in previous studies, to operate an microbial fuel cell (MFC) sensor for
      real-time nitrate monitoring, and achieved surprisingly greater sensitivity (4.42
      +/- 0.3-6.66 +/- 0.4 mV/(mg/L)) when the nitrate was at a concentration of 10-40
      mg/L, compared to that of the MFC sensor with a closed circuit (0.8 +/- 0.05-1.6
      +/- 0.1 mV/(mg/L)). The MFC sensor operated in open circuit (O-MFC sensor)
      delivered much more stable performance than that operated in closed circuit (C
      MFC sensor) when affected by organic matter (NaAc). The sensitivity of O-MFC
      sensor was twice that of C-MFC sensor at a low background concentration of
      organic matter. When organic matter reached a high concentration, the sensitivity
      of O-MFC sensor remained at an acceptable level, while that of C-MFC sensor
      dropped to almost zero. Challenged by a combined shock of organic matter and
      nitrate, O-MFC sensor delivered evident electrical signals for nitrate warning,
      while C-MFC failed. Another novel feature of this study lies in a new
      mathematical model to examine the bioanode process of nitrate monitoring. It
      revealed that lower capacitance of the bioanode in O-MFC was the major
      contributor to the improved sensitivity of the device.

PMID- 29660587
TI  - Photochemical interaction of ascorbic acid and nicotinamide in aqueous solution:
      A kinetic study.
AB  - The photodegradation of ascorbic acid (AH2) in the presence of nicotinamide (NA)
      at pH 2.0-12.0 has been studied using a 30 W UV radiation source. The reaction
      follows first-order kinetics and the values of apparent first-order rate
      constants (kobs) at 1 * 10-3 M NA concentration range from 1.17 (pH 2.0) to 3.61
      * 10-3 min-1 (pH 12.0). The values of these rate constants (k0) in the absence of
      NA range from 0.50 (pH 2.0) to 1.75 * 10-3 min-1 (pH 12.0), indicating that the
      values of kobs for the photodegradation of AH2 in the presence of NA are about 2
      fold compared to those of the AH2 alone. The second-order rate constants (k') for
      the photochemical interaction of AH2 and NA are in the range of 0.67 (pH 2.0) and
      1.86 * 10-3 M-1 min-1 (pH 12.0). The k'-pH profile shows a gradual increase in
      the rate as a function of pH. This is due to the ionization of AH2 to give
      ascorbyl anions (AH-) which are more susceptible to photodegradation compared to
      the neutral molecule (AH2). NA appears to undergo photochemical interaction with
      AH2 during the reaction by acting as an electron acceptor to enhance its rate of
      photodegradation. The concentrations of AH2 and NA in degraded solutions have
      been determined by a two-component spectrometric method at 243 and 261 nm (pH
      2.0) with a precision of +/-2%. The method has been validated and the results are
      comparable to the HPLC method.

PMID- 29660588
TI  - Chemically synthesized butein and butin: Optical, structure and electrochemical
      redox functionality at electrode interface.
AB  - Progress in the development of phytochemistry has delivered advancement in
      materials functionality for range of inter/trans-disciplinary application. Here,
      we investigated the structural functionality of chemically synthesized
      phytoconstitutent, chalcone (butein) and flavanone (butin). Photoactive and
      electroactive behavior of butein and butin were comprehensively studied using UV
      vis absorbance, photoluminescence and cyclic voltammetric techniques. Surface
      morphology of the butein and butin powders was characterized from scanning
      electron microscope at an operating voltage of 10 kV. Significant ultraviolet
      absorbance property are observed from butein and butin due to the distribution of
      pi -> pi* and n -> pi* transitions. Photoluminescence emission spectra of the
      prepared materials are well resolved at visible region via keto-enol
      tautomerization and can be influenced by solvent pH. Cyclic voltammetric studies
      on the prepared materials enabled a direct electron-transfer reaction at gold
      screen printed electrode, indicating the feasibility for analytical validation in
      herbal industries. Existence of multiple electroactive hydroxyl groups makes
      butein and butin a redox-functional species at electrode interface. Dispersion
      ability in aqueous and organic solvents makes butein and butin suitable for
      variety of photochemical applications. This phytochemical material offers new
      degrees of optical and redox functionality similar to inorganic nanostructures,
      in addition to inherent bioactivity, that may be advantageous for further
      biomedical function.

PMID- 29660590
TI  - Detection of neurodevelopmental diversity in memory clinics-Validation of a self
      report measure.
AB  - BACKGROUND: Neurodevelopmental learning and attentional disorders (NLAD) such as
      dyslexia, dyscalculia and attention deficit hyperactivity disorder (ADHD) affect
      at least 6% of the adult population or more. They are associated with atypical
      cognitive patterns in early and adult life. The cognitive patterns of affected
      individuals in late life have never been described. One main challenge is
      detecting individuals in clinical settings during which mild cognitive changes
      could be confounding the clinical presentation. This is a critical research gap
      because these conditions interact, across the life course, with an individual's
      risk for dementia. Also, learning disabilities which present in childhood pose
      persistent cognitive differences in areas involving executive function, reading
      and math. Clinicians lack tools to detect undiagnosed neurodevelopmental in
      adults with memory disorders. The majority of patients presenting at memory
      clinics today come from a generation during which NLAD were not yet clinically
      recognized. In this study, we hypothesized that a self-report scale can detect
      NLAD in a memory clinic population. METHODS: We developed a self-report,
      retrospective childhood cognitive questionnaire including key attributes adapted
      from prior validated measures. 233 participants were included in the primary
      analysis. RESULTS: Confirmatory Factor Analysis resulted in a best-fit model with
      six labelled factors (Math, Language, Attention, Working Memory, Sequential
      Processing, and Executive Function) and 15 total question items. The model
      demonstrated unidimensionality, reliability, convergent validity, discriminant
      validity, and predictive validity. Using 1.5 standard deviations as the cut-off,
      subjects were categorized into: Normal (n = 169), Language (n = 10), Math (n =
      12), Attention (n = 10) or Other/Mixed (n = 32). CONCLUSION: A self-report
      measure can be a useful tool to elicit childhood cognitive susceptibilities in
      various domains that could represent NLAD among patients in a memory clinic
      setting, even in the presence of mild cognitive impairment.

PMID- 29660589
TI  - Predicting reading ability in teenagers who are deaf or hard of hearing: A
      longitudinal analysis of language and reading.
AB  - BACKGROUND: Deaf and hard of hearing (D/HH) children and young people are known
      to show group-level deficits in spoken language and reading abilities relative to
      their hearing peers. However, there is little evidence on the longitudinal
      predictive relationships between language and reading in this population. AIMS:
      To determine the extent to which differences in spoken language ability in
      childhood predict reading ability in D/HH adolescents. METHODS: and procedures:
      Participants were drawn from a population-based cohort study and comprised 53
      D/HH teenagers, who used spoken language, and a comparison group of 38 normally
      hearing teenagers. All had completed standardised measures of spoken language
      (expression and comprehension) and reading (accuracy and comprehension) at 6-10
      and 13-19 years of age. OUTCOMES: and results: Forced entry stepwise regression
      showed that, after taking reading ability at age 8 years into account, language
      scores at age 8 years did not add significantly to the prediction of Reading
      Accuracy z-scores at age 17 years (change in R2 = 0.01, p = .459) but did make a
      significant contribution to the prediction of Reading Comprehension z-scores at
      age 17 years (change in R2  = 0.17, p < .001). CONCLUSIONS: and implications: In
      D/HH individuals who are spoken language users, expressive and receptive language
      skills in middle childhood predict reading comprehension ability in adolescence.
      Continued intervention to support language development beyond primary school has
      the potential to benefit reading comprehension and hence educational access for
      D/HH adolescents.

PMID- 29660591
TI  - Inverse relationship between the evans index and cognitive performance in non
      disabled, stroke-free, community-dwelling older adults. A population-based study.
AB  - OBJECTIVE: The Evans Index (EI) is used for recognition of individuals with
      normal pressure hydrocephalus. However, recent studies suggest that the EI is not
      a reliable marker of this condition. Rather, the EI may be inversely correlated
      with cognitive performance, but information on this correlation is lacking. We
      aimed to assess the relationship between the EI and cognitive performance in
      community-dwelling older adults. PATIENTS AND METHODS: The study included 314 non
      disabled, stroke-free, individuals aged >=60 years enrolled in the Atahualpa
      Project undergoing brain MRI and MoCA testing. Using generalized linear models,
      adjusted for demographics, cardiovascular risk factors edentulism, depression,
      global cortical atrophy and white matter hyperintensities of vascular origin, we
      assessed the relationship between the EI and cognitive performance. Predictive
      margins of the MoCA score according to percentiles of the EI were also evaluated,
      after adjusting for variables reaching significance in univariate models.
      RESULTS: The mean EI was 0.248 +/- 0.022 and the mean MoCA score was 19.7 +/- 4.8
      points. A fully-adjusted generalized linear model showed a significant inverse
      relationship between the EI and the MoCA score. Predictive models showed a
      decrease in the MoCA score according to increased levels of the EI (beta: -3.28;
      95% C.I.: -6.09 to -0.47; p = 0.022). CONCLUSION: The independent effect of the
      EI on the MoCA score provides evidence of the utility of the EI to evaluate
      cognitive performance.

PMID- 29660592
TI  - Declining trends in drug dealing among adolescents in the United States.
AB  - INTRODUCTION: The link between drug selling and other delinquent behaviors in
      adolescence is well established. Less is known regarding the trends in drug
      selling among youth in the US and whether they are consistent with the recently
      observed decline in problem behaviors among this population. METHODS: Data were
      collected between 2002 and 2015 as part of the National Survey on Drug Use and
      Health (NSDUH). Participants included 233,435 US youth aged 12-17. The primary
      variable of interest was self-reported past year drug-selling. Logistic
      regression assessed trends in drug-selling among male and female subgroups.
      RESULTS: Between 2002 and 2015, the prevalence of drug-selling decreased
      significantly across all youth (AOR = 0.970, p < .001). Analysis of gender
      differences revealed that the rate of drug-selling decreased significantly among
      boys (AOR = 0.962, p < .001), however, the trend remained stable for girls (AOR =
      0.987, p > .05). The decrease in drug-selling was observed for nearly all male
      subgroups, African-American girls (0.946, p < .01) and girls reporting no illegal
      substance use in the past year (0.960, p < .05). CONCLUSIONS: The prevalence of
      past year drug-selling among youth in the US is declining significantly,
      especially for boys.

PMID- 29660594
TI  - Methodological factors as a potential source of discordance between self-report
      and behavioral measures of impulsivity and related constructs.
AB  - There is a consistent but poorly understood finding that self-report and
      behavioral measures of impulsivity are weakly correlated or uncorrelated. There
      are many possible explanations for this observation, including differences in how
      these instruments are administered and scored. The present study examined the
      utility of alternative scoring algorithms for self-report measures that aim to
      identify participants' peak impulsivity (or self-control), informed by estimates
      of item difficulty from Item Response Theory (IRT) analyses. College students
      were administered self-report questionnaires (Zuckerman Sensation Seeking Scale
      [ZSS], Barratt Impulsiveness Scale [BIS-11], behavioral measures related to risk
      taking and impulsivity (Balloon Analog Risk Task [BART], Experiential Discounting
      Task [EDT]), and the substance use module of a clinical interview (past-six-month
      alcohol and marijuana use). IRT analyses were conducted on self-report measures
      to estimate item difficulty. Scoring algorithms ranked items by difficulty and
      scored items based on consecutive items endorsed or denied. A maximal scoring
      algorithm increased the concordance between the BIS-11 and BART (r = 0.08 vs. 
      0.07), but there was no evidence of increased incremental validity for substance
      use. Findings suggest that methodological factors may help explain the poor
      concordance of self-report and behavioral measures of impulsivity, but the
      magnitude of these correlations remained quite small. Further, alternative
      scoring algorithms were correlated with substance use but did not explain any
      variance that was distinct from typical algorithms. Future directions are
      discussed for elucidating the discrepancy between self-report and behavioral
      measures of impulsivity-related constructs, such as using large self-report item
      pools to develop computer adaptive tests.

PMID- 29660593
TI  - Factors associated with hazardous alcohol use and motivation to reduce drinking
      among HIV primary care patients: Baseline findings from the Health & Motivation
      study.
AB  - BACKGROUND: Limited primary care-based research has examined hazardous drinking
      risk factors and motivation to reduce use in persons with HIV (PWH). METHODS: We
      computed prevalence ratios (PR) for factors associated with recent (<30 days)
      hazardous alcohol use (i.e., 4+/5+ drinks in a single day for women/men),
      elevated Alcohol Use Disorders Identification Test (AUDIT) scores, and importance
      and confidence (1-10 Likert scales) to reduce drinking among PWH in primary care.
      RESULTS: Of 614 participants, 48% reported recent hazardous drinking and 12%
      reported high alcohol use severity (i.e., AUDIT zone 3 or higher). Factors
      associated with greater alcohol severity included moderate/severe anxiety (PR:
      2.07; 95% CI: 1.18, 3.63), tobacco use (PR: 1.79; 1.11, 2.88), and other
      substance use (PR: 1.72; 1.04, 2.83). Factors associated with lower alcohol
      severity included age 50-59 years (PR: 0.46; 0.22, 2.00) compared with age 20-39
      years, and having some college/college degree (PR: 0.61; 0.38, 0.97) compared
      with <=high school. Factors associated with greater importance to reduce drinking
      (scores >5) included: moderate/severe depression (PR: 1.43; 1.03, 2.00) and other
      substance use (PR: 1.49; 1.11, 2.01). Lower importance was associated with
      incomes above $50,000 (PR: 0.65; 0.46, 0.91) and marijuana use (PR: 0.65; 0.49,
      0.87). HIV-specific factors (e.g., CD4 and HIV RNA levels) were not associated
      with alcohol outcomes. CONCLUSIONS: This study identified modifiable participant
      characteristics associated with alcohol outcomes in PWH, including anxiety and
      depression severity, tobacco use, and other substance use.

PMID- 29660595
TI  - Computer-assisted subtyping and prognosis for non-small cell lung cancer patients
      with unresectable tumor.
AB  - BACKGROUND: The histological classification or subtyping of non-small cell lung
      cancer is essential for systematic therapy decisions. Differentiating between the
      two main subtypes of pulmonary adenocarcinoma and squamous cell carcinoma
      highlights the considerable differences that exist in the prognosis of patient
      outcomes. Physicians rely on a pathological analysis to reveal these phenotypic
      variations that requires invasive methods, such as biopsy and resection sample,
      but almost 70% of tumors are unresectable at the point of diagnosis. METHOD: A
      computational method that fuses two frameworks of computerized subtyping and
      prognosis was proposed, and it was validated against publicly available dataset
      in The Cancer Imaging Archive that consisted of 82 curated patients with CT
      scans. The accuracy of the proposed method was compared with the gold standard of
      pathological analysis, as defined by theInternational Classification of Disease
      for Oncology (ICD-O). A series of survival outcome test cases were evaluated
      using the Kaplan-Meier estimator and log-rank test (p-value) between the
      computational method and ICD-O. RESULTS: The computational method demonstrated
      high accuracy in subtyping (96.2%) and good consistency in the statistical
      significance of overall survival prediction for adenocarcinoma and squamous cell
      carcinoma patients (p < 0.03) with respect to its counterpart pathological
      subtyping (p < 0.02). The degree of reproducibility between prognosis taken on
      computational and pathological subtyping was substantial with an averaged
      concordance correlation coefficient (CCC) of 0.9910. CONCLUSION: The findings in
      this study support the idea that quantitative analysis is capable of representing
      tissue characteristics, as offered by a qualitative analysis.

PMID- 29660597
TI  - Risk stratification of sentinel node-positive melanoma patients defines surgical
      management and adjuvant therapy treatment considerations.
AB  - BACKGROUND: In light of the evolving landscape of adjuvant therapy in melanoma
      and the recently confirmed absent survival benefit of completion lymph node
      dissection (CLND), it becomes important to explore possible consequences of
      omitting CLND, and whether it is possible to adequately stratify positive
      sentinel node (SN) patients solely based on information retrieved from the
      melanoma up to the sentinel lymph node biopsy (SLNB). METHODS: A retrospective
      cohort from nine European Organization for Research and Treatment of Cancer
      Melanoma Group centres was used. Patients were staged based on SLNB and CLND
      result according to the American Joint Committee on Cancer (AJCC) criteria and
      stratified by ulceration and SN tumour burden. These were incorporated in Cox
      regression models. Predictive ability was assessed using Harrell's concordance
      index (c-index) and the Akaike information criterion (AIC). RESULTS: In total,
      1015 patients were eligible. CLND led to upstaging in N-category in 19% and in
      AJCC stage in 5-6%. The model incorporating only ulceration and SN tumour burden
      performed equally well as the model incorporating substages after CLND. The model
      incorporating substages based on SLNB had the lowest predictive ability.
      Stratifying by ulceration and SN tumour burden resulted in four positive SN
      groups from which low-, intermediate- and high-risk prognostic classes could be
      derived. CONCLUSIONS: Adequate stratification of positive SN patients was
      possible based on ulceration and SN tumour burden category. The identification of
      low-, intermediate- and high-risk patients could guide adjuvant therapy in
      clinical practice. Omitting CLND seems to have little consequences.

PMID- 29660596
TI  - Time trends of overall survival among metastatic breast cancer patients in the
      real-life ESME cohort.
AB  - AIM: Real-life analysis of overall survival (OS) trends among metastatic breast
      cancer (MBC) patients may help define medical needs and evaluate the impact of
      public health investments. The present study aimed to evaluate the independent
      impact of the year of MBC diagnosis on OS in the Epidemio-Strategy-Medical
      Economical (ESME)-MBC cohort. METHODS: ESME-MBC (NCT03275311) is a French,
      national, multicentre, observational cohort including 16,702 consecutive newly
      diagnosed MBC patients (01 January 2008-31 December 2014). Of 16,680 eligible
      patients, 15,085 had full immunohistochemistry data, allowing classification as
      hormone receptor-positive and HER2-negative (HR+/HER2-, N = 9907), HER2-positive
      (HER2+, N = 2861) or triple-negative (HR-/HER2-, N = 2317) subcohorts.
      Multivariate analyses of OS were conducted among the full ESME cohort and
      subcohorts. RESULTS: Median OS of the whole cohort was 37.22 months (95%
      confidence interval [CI], 36.3-38.04). Year of diagnosis was an independent
      predictor of OS (hazard ratio 0.98 [95% CI, 0.97-1.00], P = .01) together with
      age, subtype, disease-free interval, visceral metastases and number of organs
      involved. Median OS of HR+/HER2-, HER2+ and HR-/HER2- subcohorts was,
      respectively, 42.12 (95% CI, 40.90-43.10), 44.91 (95% CI, 42.51-47.90) and 14.52
      (95% CI, 13.70-15.24) months. Year of diagnosis was a strong independent
      predictor of OS in HER2+ subcohort (hazard ratio 0.91 [95% CI, 0.88-0.94], P <
      .001), but not in HR+/HER2- nor HR-/HER2- subcohorts (hazard ratio 1.00 [95% CI,
      0.98-1.01], P = .80 and 1.00 [95% CI, 0.97-1.02], P = .90, respectively).
      CONCLUSIONS: The OS of MBC patients has slightly improved over the past decade.
      However, this effect is confined to HER2+ cases, highlighting the need of new
      strategies in the other subtypes.

PMID- 29660598
TI  - First-in human, phase 1, dose-escalation pharmacokinetic and pharmacodynamic
      study of the oral dual PI3K and mTORC1/2 inhibitor PQR309 in patients with
      advanced solid tumors (SAKK 67/13).
AB  - BACKGROUND: PQR309 is an orally bioavailable, balanced pan-phosphatidylinositol-3
      kinase (PI3K), mammalian target of rapamycin (mTOR) C1 and mTORC2 inhibitor.
      PATIENTS AND METHODS: This is an accelerated titration, 3 + 3 dose-escalation,
      open-label phase I trial of continuous once-daily (OD) PQR309 administration to
      evaluate the safety, pharmacokinetics (PK) and pharmacodynamics in patients with
      advanced solid tumours. Primary objectives were to determine the maximum
      tolerated dose (MTD) and recommended phase 2 dose (RP2D). RESULTS: Twenty-eight
      patients were included in six dosing cohorts and treated at a daily PQR309 dose
      ranging from 10 to 150 mg. Common adverse events (AEs; >=30% patients) included
      fatigue, hyperglycaemia, nausea, diarrhoea, constipation, rash, anorexia and
      vomiting. Grade (G) 3 or 4 drug-related AEs were seen in 13 (46%) and three (11%)
      patients, respectively. Dose-limiting toxicity (DLT) was observed in two patients
      at 100 mg OD (>14-d interruption in PQR309 due to G3 rash, G2
      hyperbilirubinaemia, G4 suicide attempt; dose reduction due to G3 fatigue, G2
      diarrhoea, G4 transaminitis) and one patient at 80 mg (G3 hyperglycaemia >7 d).
      PK shows fast absorption (Tmax 1-2 h) and dose proportionality for Cmax and area
      under the curve. A partial response in a patient with metastatic thymus cancer,
      24% disease volume reduction in a patient with sinonasal cancer and stable
      disease for more than 16 weeks in a patient with clear cell Bartholin's gland
      cancer were observed. CONCLUSION: The MTD and RP2D of PQR309 is 80 mg of orally
      OD. PK is dose-proportional. PD shows PI3K pathway phosphoprotein downregulation
      in paired tumour biopsies. Clinical activity was observed in patients with and
      without PI3K pathway dysregulation. CLINICAL TRIAL REGISTRATION:
      ClinicalTrials.gov # NCT01940133.

PMID- 29660599
TI  - Dosage-dependent reduction of macular pigment optical density in female breast
      cancer patients receiving tamoxifen adjuvant therapy.
AB  - It is now increasingly common for breast cancer patients to receive adjuvant
      tamoxifen therapy for a period of up to 10 years. As survival rate increases,
      managing tamoxifen ocular toxicities is important for patients' quality of life.
      Macular pigments in photoreceptor cells protect against free radical damage,
      which can cause macular degeneration. By reducing macular pigment concentration,
      tamoxifen may increase the risk of macular degeneration. Here, we compared
      macular pigment optical density (MPOD) and central macular thickness between
      breast cancer patients on tamoxifen adjuvant therapy (n = 70), and a control
      group (n = 72). Multiple regression analysis indicated that MPOD decreases with
      increasing tamoxifen dosage, up to a threshold of about 20 g, after which MPOD
      plateaus out. Mean MPOD in the treatment group (mean = 0.40) was significantly
      lower (p-value = 0.02) compared to the control group (mean = 0.47) for the left
      eye, and for the right eye (treatment mean = 0.39; control mean = 0.48; p-value =
      0.009). No significant difference in mean central macular thickness was found
      between the treatment and the control group (p-values > 0.4). In the control
      group, MPOD and central macular thickness showed significant correlation (r~0.30;
      p-values < 0.01) for both eyes. However, in the treatment group, loss of
      significant correlation was observed in the left eye (r = 0.21; p-value = 0.08).
      The present results show that MPOD decreases non-linearly as a function of
      tamoxifen dosage, and highlight the potential of tamoxifen to reduce macular
      pigment concentration through an unknown mechanism that does not depend on
      macular thinning solely.

PMID- 29660600
TI  - Holographic imaging and photostimulation of neural activity.
AB  - Optical imaging methods are powerful tools in neuroscience as they can
      systematically monitor the activity of neuronal populations with high
      spatiotemporal resolution using calcium or voltage indicators. Moreover, caged
      compounds and optogenetic actuators enable to optically manipulate neural
      activity. Among optical methods, computer-generated holography offers an enormous
      flexibility to sculpt the excitation light in three-dimensions (3D), particularly
      when combined with two-photon light sources. By projecting holographic light
      patterns on the sample, the activity of multiple neurons across a 3D brain volume
      can be simultaneously imaged or optically manipulated with single-cell precision.
      This flexibility makes two-photon holographic microscopy an ideal all-optical
      platform to simultaneously read and write activity in neuronal populations in
      vivo in 3D, a critical ability to dissect the function of neural circuits.

PMID- 29660601
TI  - A QCM-D study of the concentration- and time-dependent interactions of human LL37
      with model mammalian lipid bilayers.
AB  - The human antimicrobial peptide LL37 is promising as an alternative to
      antibiotics due to its biophysical interactions with charged bacterial lipids.
      However, its clinical potential is limited due to its interactions with
      zwitterionic mammalian lipids leading to cytotoxicity. Mechanistic insight into
      the LL37 interactions with mammalian lipids may enable rational design of less
      toxic LL37-based therapeutics. To this end, we studied concentration- and time
      dependent interactions of LL37 with zwitterionic model phosphatidylcholine (PC)
      bilayers with quartz crystal microbalance with dissipation (QCM-D). LL37 mass
      adsorption and PC bilayer viscoelasticity changes were monitored by measuring
      changes in frequency (Deltaf) and dissipation (DeltaD), respectively. The Voigt
      Kelvin viscoelastic model was applied to Deltaf and DeltaD to study changes in
      bilayer thickness and density with LL37 concentration. At low concentrations
      (0.10-1.00 MUM), LL37 adsorbed onto bilayers in a concentration-dependent manner.
      Further analyses of Deltaf, DeltaD and thickness revealed that peptide saturation
      on the bilayers was a threshold for interactions observed above 2.00 MUM,
      interactions that were rapid, multi-step, and reached equilibrium in a
      concentration- and time-dependent manner. Based on these data, we proposed a
      model of stable transmembrane pore formation at 2.00-10.0 MUM, or transition from
      a primarily lipid to a primarily protein film with a transmembrane pore formation
      intermediate state at concentrations of LL37 > 10 MUM. The concentration
      dependent interactions between LL37 and PC bilayers correlated with the observed
      concentration-dependent biological activities of LL37 (antimicrobial,
      immunomodulatory and non-cytotoxic at 0.1-1.0 MUM, hemolytic and some
      cytotoxicity at 2.0-13 MUM and cytotoxic at >13 MUM).

PMID- 29660603
TI  - Both alcoholic and non-alcoholic steatohepatitis association with cardiovascular
      risk and liver fibrosis.
AB  - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of
      liver disease worldwide. Mortality in NAFLD is mainly related to cardiovascular
      disease (CVD) and cancer. NAFLD and its association with both CVD and liver
      disease risk have been well evaluated, but the association of NAFLD with alcohol,
      known as "both alcoholic and non-alcoholic steatohepatitis" (BASH), remains
      uncertain. The objective of this study was to assess the influence of alcohol and
      obesity in the development of liver and cardiovascular disease risk. METHODS:
      This was a case-control study that included patients from a regular check-up.
      Alcohol consumption was evaluated with MAST, AUDIT, and CAGE. Cardiovascular risk
      was evaluated using the Framingham score, and liver fibrosis was evaluated with
      APRI and NAFLD score. Patients were classified in five groups: healthy patients,
      steatosis with obesity, steatosis with alcoholism, BASH, and idiopathic
      steatosis. RESULTS: A total of 414 patients were included. The BASH group
      represented 16% of patients, and showed a greater proportion of patients with
      high cardiovascular risk with 17% (p = 0.001), and liver fibrosis with 9%,
      according to the APRI score (p = 0.10). A multivariate logistic regression showed
      that alcohol consumption >140 g/week (OR 2.546, 95% CI 1.11-5.81, p = 0.003) and
      BMI >25 kg/m2 (OR 12.64, 95% CI 1.66 96.20, p = 0.001) were related to high
      cardiovascular risk. Liver fibrosis according to APRI was only related to alcohol
      consumption >140 g/week (OR 2.74, 95% CI 1-7.48, p = 0.03). CONCLUSIONS: BASH
      remains an area not well explored, and of great implication given the increasing
      number of patients affected. We observed an additive effect of both etiologies in
      the development of high cardiovascular and liver disease risk.

PMID- 29660602
TI  - Astrocyte pathology in the ventral prefrontal white matter in depression.
AB  - Astrocyte functions in white matter are less well understood than in gray matter.
      Our recent study of white matter in ventral prefrontal cortex (vPFC) revealed
      alterations in expression of myelin-related genes in major depressive disorder
      (MDD). Since white matter astrocytes maintain myelin, we hypothesized that
      morphometry of these cells will be altered in MDD in the same prefrontal white
      matter region in which myelin-related genes are altered. White matter adjacent to
      vPFC was examined in 25 MDD and 21 control subjects. Density and size of GFAP
      immunoreactive (-ir) astrocyte cell bodies was measured. The area fraction of
      GFAP-ir astrocytes (cell bodies + processes) was also estimated. GFAP mRNA
      expression was determined using qRT-PCR. The density of GFAP-ir astrocytes was
      also measured in vPFC white matter of rats subjected to chronic unpredictable
      stress (CUS) and control animals. Fibrous and smooth GFAP-ir astrocytes were
      distinguished in human white matter. The density of both types of astrocytes was
      significantly decreased in MDD. Area fraction of GFAP immunoreactivity was
      significantly decreased in MDD, but mean soma size remained unchanged. Expression
      of GFAP mRNA was significantly decreased in MDD. In CUS rats there was a
      significant decrease in astrocyte density in prefrontal white matter. The
      decrease in density and area fraction of white matter astrocytes and GFAP mRNA in
      MDD may be linked to myelin pathology previously noted in these subjects.
      Astrocyte pathology may contribute to axon disturbances in axon integrity
      reported by neuroimaging studies in MDD and interfere with signal conduction in
      the white matter.

PMID- 29660604
TI  - Response time distribution parameters show posterror behavioral adjustment in
      mental arithmetic.
AB  - After making an error, we usually slow down before our next response. This
      phenomenon is known as the posterror slowing (PES) effect. It has been
      interpreted to be an indicator of posterror behavioral adjustments and,
      therefore, has been linked to cognitive control. However, contradictory findings
      regarding PES and posterror accuracy cast doubt on such a relation. To determine
      whether behavior is adjusted after making an error, we investigated other
      features of behavior, such as the distribution of response times (RT) in a mental
      arithmetic task. Participants performed an arithmetic task with (Experiments 1
      and 2) and without (Experiment 1) an accuracy-tracking procedure. On both tasks,
      participants responded more slowly and less accurately after errors. However, the
      RT distribution was more symmetrical on posterror trials compared to postcorrect
      trials, suggesting that a change in processing mode occurred after making an
      error, thus linking cognitive control to error monitoring, even in cases when
      accuracy decreased after errors. These findings expand our understanding on how
      posterror behavior is adjusted in mental arithmetic, and we propose that the
      measures of the RT distribution can be further used in other domains of error
      monitoring research.

PMID- 29660605
TI  - Functional assessment of spermatogonial stem cell purity in experimental cell
      populations.
AB  - Historically, research in spermatogonial biology has been hindered by a lack of
      validated approaches to identify and isolate pure populations of the various
      spermatogonial subsets for in-depth analysis. In particular, although a number of
      markers of the undifferentiated spermatogonial population have now been
      characterized, standardized methodology for assessing their specificity to the
      spermatogonial stem cell (SSC) and transit amplifying progenitor pools has been
      lacking. To date, SSC content within an undefined population of spermatogonia has
      been inferred using either lineage tracing or spermatogonial transplantation
      analyses which generate qualitative and quantitative data, respectively.
      Therefore, these techniques are not directly comparable, and are subject to
      variable interpretations as to a readout that is representative of a 'pure' SSC
      population. We propose standardization across the field for determining the SSC
      purity of a population via use of a limiting dilution transplantation assay that
      would eliminate subjectivity and help to minimize the generation of inconsistent
      data on 'SSC' populations. In the limiting dilution transplantation assay, a
      population of LacZ-expressing spermatogonia are selected based on a putative SSC
      marker, and a small, defined number of cells (i.e. 10 cells) are microinjected
      into the testis of a germ cell-deficient recipient mouse. Using colony counts and
      an estimated colonization efficiency of 5%; a quantitative value can be
      calculated that represents SSC purity in the starting population. The utilization
      of this technique would not only be useful to link functional relevance to novel
      markers that will be identified in the future, but also for providing validation
      of purity for marker-selected populations of spermatogonia that are commonly
      considered to be SSCs by many researchers in the field of spermatogenesis and
      stem cell biology.

PMID- 29660606
TI  - Generation of induced pluripotent stem cells from a patient with Best Dystrophy
      carrying 11q12.3 (BEST1 (VMD2)) mutation.
AB  - Best disease (BD), also termed Best vitelliform macular dystrophy (BVMD), is a
      juvenile-onset form of macular degeneration and central visual loss. In this
      report, we generated an induced pluripotent stem cell (iPSC) line, TVGH-iPSC-012
      04, from the peripheral blood mononuclear cells of a female patient with BD by
      using the Sendai virus delivery system. The resulting iPSCs retained the disease
      causing DNA mutation, expressed pluripotent markers and could differentiate into
      three germ layers. We believe that BD patient-specific iPSCs provide a powerful
      in vitro model for evaluating the pathological phenotypes of the disease.

PMID- 29660607
TI  - Generation of an iPS cell line via a non-integrative method using urine-derived
      cells from a patient with USH2A-associated retinitis pigmentosa.
AB  - We have established an induced pluripotent stem (iPS) cell line using urine
      derived cells from a 27-year-old male patient with retinitis pigmentosa
      associated with point mutations in the USH2A gene. Feeder-free culture conditions
      and the integration-free CytoTuneTM-iPS 2.0 Sendai Reprogramming Kit were used.

PMID- 29660608
TI  - Generation and characterization of two human iPSC lines from patients with
      methylmalonic acidemia cblB type.
AB  - Two human induced pluripotent stem cell (iPSC) lines were generated from
      fibroblasts of two siblings with methylmalonic acidemia cblB type carrying
      mutations in the MMAB gene: c.287T?C (p.Ile96Thr) and a splicing loss-of-function
      variant c.584G?A affecting the last nucleotide of exon 7 in MMAB
      (p.Ser174Cysfs*23). Reprogramming factors OCT3/4, SOX2, KLF4 and c-MYC were
      delivered using a non-integrative method based on the Sendai virus. Once
      established, iPSCs have shown full pluripotency, differentiation capacity and
      genetic stability.

PMID- 29660609
TI  - Aflatoxin B1-contaminated diet disrupts the blood-brain barrier and affects fish
      behavior: Involvement of neurotransmitters in brain synaptosomes.
AB  - It is known that the cytotoxic effects of aflatoxin B1 (AFB1) in endothelial
      cells of the blood-brain barrier (BBB) are associated with behavioral
      dysfunction. However, the effects of a diet contaminated with AFB1 on the
      behavior of silver catfish remain unknown. Thus, the aim of this study was to
      evaluate whether an AFB1-contaminated diet (1177 ppb kg feed-1) impaired silver
      catfish behavior, as well as whether disruption of the BBB and alteration of
      neurotransmitters in brain synaptosomes are involved. Fish fed a diet
      contaminated with AFB1 presented a behavioral impairment linked with
      hyperlocomotion on days 14 and 21 compared with the control group (basal diet).
      Neurotransmitter levels were also affected on days 14 and 21. The permeability of
      the BBB to Evans blue dye increased in the intoxicated animals compared with the
      control group, which suggests that the BBB was disrupted. Moreover,
      acetylcholinesterase (AChE) activity in brain synaptosomes was increased in fish
      fed a diet contaminated with AFB1, while activity of the sodium-potassium pump
      (Na+, K+-ATPase) was decreased. Based on this evidence, the present study shows
      that silver catfish fed a diet containing AFB1 exhibit behavioral impairments
      related to hyperlocomotion. This diet caused a disruption of the BBB and brain
      lesions, which may contribute to the behavioral changes. Also, the alterations in
      the activities of AChE and Na+, K+-ATPase in brain synaptosomes may directly
      contribute to this behavior, since they may promote synapse dysfunction. In
      addition, the hyperlocomotion may be considered an important macroscopic marker
      indicating possible AFB1 intoxication.

PMID- 29660610
TI  - DNA damaging and apoptotic potentials of Bisphenol A and Bisphenol S in human
      bronchial epithelial cells.
AB  - DNA damage caused by environmental agents often lead to many chronic diseases,
      including cancer. The present study aimed to understand the relative toxicity
      possessed by Bisphenol A (BPA) and Bisphenol S (BPS) on human bronchial
      epithelial cells (BEAS-2B). The cells were exposed to either BPA or BPS and
      evaluated for its cytotoxicity, reactive oxygen species (ROS), DNA fragmentation,
      phosphorylated histone protein (gamma-H2AX) and DNA tail damage levels. Further,
      we also studied DNA damage response (DDR) and caspase-3 mechanisms, to evaluate
      its mechanism of cell death processes. Exposure with 200 MUM of BPA,
      significantly (p < 0.05) induces caspase-3-mediated cell death by inducing
      cytotoxicity, ROS, and DNA fragmentation. Higher levels of gamma-H2AX and DNA
      tail damage indicated BPA's DNA damaging potential through an ATM/ATR/Chk1/p53
      dependent pathway in BEAS-2B cells. Overall, in vitro data exhibited moderate
      toxicity for BPS in comparison with BPA suggesting the need for a thorough
      clinical investigation over its safety profile.

PMID- 29660611
TI  - Effect of in vivo exposure to ambient fine particles (PM2.5) on the density of
      dopamine D2-like receptors and dopamine-induced [35S]-GTPgammaS binding in rat
      prefrontal cortex and striatum membranes.
AB  - Male Sprague-Dawley rats (8-9 weeks-old) were exposed for three days (acute
      exposure) or eight weeks (subchronic exposure) to purified air or concentrated
      ambient fine particles, PM2.5 (<=2.5 MUm; 15 to 18-fold of ambient air; 370-445
      MUg/m3). In membranes from rat prefrontal cortex (PFC) or striatum, the density
      and function of dopamine D2-like receptors (D2Rs) were assessed by [3H]-spiperone
      binding and dopamine-stimulated [35S]-GTPgammaS binding, respectively. Glial
      activation was evaluated by immunoperoxidase labeling of the glial fibrillary
      acidic protein (GFAP). In the PFC, no significant changes in D2R density or
      signaling were observed after the acute and subchronic exposure to PM2.5. In the
      striatum, acute exposure to PM2.5 decreased D2R density, with no effect on
      signaling efficacy, whereas subchronic exposure did not affect D2R density but
      reduced signaling efficacy. Both acute and subchronic exposure to PM2.5 induced
      reactive gliosis in the striatum but not in the PFC. These results indicate that
      exposure to PM2.5 induces astrocyte activation and alters striatal dopaminergic
      transmission.

PMID- 29660613
TI  - Effects of human activities and climate change on the reduction of visibility in
      Beijing over the past 36 years.
AB  - Both climate change and intensive human activities are thought to have
      contributed to the impairment of atmospheric visibility in Beijing. But the
      detailed processes involved and relative roles of human activities and climate
      change have not been quantified. Optical extinction of aerosols, the inverse of
      meteorological visibility is especially sensitive to fine particles <1.0 MUm.
      These submicron particles are considered more hazardous than larger ones in terms
      of cardiovascular and respiratory diseases. Here we used the aerosol optical
      extinction (inverse of visibility) as the indicator of submicron particles
      pollution to estimate its inter-annual variability from 1980 to 2015. Our results
      indicated that optical extinction experienced two different periods: a weakly
      increasing stage (1980-2005) and a rapidly increasing stage (2005-2015). We
      attributed the variations of optical extinction to the joint effects of human
      activities and climate change. Over the past 36 years, human activities played a
      leading role in the increase of optical extinction, with a positive contribution
      of 0.077 km-1/10 y. While under the effects of climate change, optical extinction
      firstly decreased by 0.035 km-1/10 y until 2005 and then increased by 0.087 km
      1/10 y. Detailed analysis revealed that the abrupt change (around 2005) of
      optical extinction resulted from the trend reversals of climate change. We found
      since 2005 the decreasing trend by 0.58 m.s-1/10 y in wind speed, the growing
      trend at 8.69%/10 y in relative humidity and the declining trend by 2.72 hPa/10 y
      in atmospheric pressure have caused the rapid increase of optical extinction. In
      brief, the higher load of fine particles <1.0 MUm in Beijing in recent decades
      could be associated with both human activities and climate change. Particularly
      after 2005, the adverse climate change aggravated the situation of submicron
      particles pollution.

PMID- 29660612
TI  - Perfluoroalkyl substances and glycemic status in pregnant Danish women: The
      Odense Child Cohort.
AB  - BACKGROUND: Perfluoroalkyl substances (PFASs) are persistent chemicals with
      suspected endocrine disrupting abilities applied in consumer products. PFASs have
      potentially modulating effects on glucose homeostasis. Insulin resistance
      prevails during third trimester of pregnancy, and this challenge of glucose
      homeostasis may reveal putative effects of PFAS concentrations on glycemic
      status. OBJECTIVE: To investigate associations between five serum PFASs and
      glucose-related outcomes in pregnant Danish women based on their risk of
      gestational diabetes mellitus (GDM). METHODS: In the prospective Odense Child
      Cohort serum concentrations of five PFASs - perfluorohexane sulfonic acid
      (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA),
      perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) - were measured
      at median gestational week (GW) 11 in pregnant women. An oral glucose tolerance
      test (OGTT) was performed at GW 28. The statistical analysis was conducted among
      158 women with high GDM risk and 160 women with low GDM risk matched by
      gestational age. Multiple linear regression models were performed to estimate
      associations between PFAS concentrations and glucose, insulin, C-peptide,
      homeostatic model of assessment of insulin resistance (HOMA-IR) and beta cell
      function (HOMA-%beta), and insulin sensitivity (Matsuda index) during the 2-h
      OGTT. RESULTS: In women with high risk for GDM, a two-fold increase in PFHxS
      concentration was significantly associated with increased fasting glucose,
      fasting insulin and HOMA-IR after adjusting for age, parity, educational level
      and pre-pregnancy BMI. Adjusting for the same confounders, a doubling in PFNA
      concentration was associated with higher fasting insulin and HOMA-%beta. In women
      with low GDM risk, no associations were found between PFAS concentrations and
      glucose-related outcomes. CONCLUSION: PFHxS and PFNA concentrations were
      associated with impaired glycemic status in metabolically vulnerable pregnant
      women and might further enhance the risk of developing GDM.

PMID- 29660614
TI  - The association between Borna Disease Virus and schizophrenia: A systematic
      review and meta-analysis.
AB  - INTRODUCTION: Schizophrenia is a disabling psychiatric disorder. The role of
      Borna Disease Virus (BDV) in the etiology of schizophrenia has been suggested by
      several studies. However, the existence of such association remained
      controversial. The present meta-analysis was conducted to evaluate this
      association. METHOD: This systematic review and meta-analysis was conducted using
      preferred reporting items for systematic reviews and meta-analysis (PRISMA).
      Online databases including Scopus, PubMed, Science direct, Embase, PsycINFO, Web
      of Science and Google scholar search engine were searched until January 15, 2017.
      The heterogeneity of the studies was evaluated using Cochran's Q test and I2
      statistic. Finally, random effects model was used for combining the results using
      Stata software version 11.1. RESULT: Overall, 30 studies containing 2533 cases
      and 4004 controls were included in the meta-analysis. The combined odds ratio
      (OR) for the relationship between BDV and schizophrenia was estimated to be 2.72
      (95%CI: 1.75-4.20). This association based on RT-PCR, WB, IFA, EIA, RLA, ECLIA
      methods was estimated to be 3.83 (95%CI: 1.59-9.20), 4.99 (95%CI: 1.80-13.85),
      1.27 (95%CI: 0.23-7.12), 2.26 (95%CI: 0.48-10.64), 1.67 (95%CI: 0.50-5.56) and
      2.88 (95%CI: 1.38-6.01), respectively. Subgroup analysis according to WBC, serum
      and plasma samples was estimated to be 3.31 (95%CI: 1.19-9.25), 2.21 (95% CI:
      1.17-4.17), 2.21 (95%CI: 1.03-4.73) and 7.89 (95%CI: 1.75-35.53), respectively.
      CONCLUSION: The results indicated the role of BDV in the etiology of
      schizophrenia.

PMID- 29660615
TI  - Biochemical and molecular alterations in freshwater mollusks as biomarkers for
      petroleum product, domestic heating oil.
AB  - To investigate the effect one of the oil products, domestic heating oil (DHO), on
      freshwater mollusks, Unio tigridis and Viviparous bengalensis were exposed to
      three DHO concentrations for each species (5.8, 8.7, and 17.4 ml L-1 for mussels;
      6.5, 9.7, and 19.5 mlL-1 for snails, respectively). Antioxidant enzymes
      (superoxide dismutase, catalase), malondialdehyde, acetylcholinesterase and DNA
      damage in both species tissues were monitored over 21 days. The results showed
      that both antioxidant enzymes concentration (SOD and CAT) increased in the lowest
      DHO concentrations (5.8, and 8.7 ml L-1), and then decreased in the highest
      concentration (17.4 ml L-1) as the same pattern for Unio tigridis, but this not
      occurred for Viviparous bengalensis. MDA values recorded significantly increased
      compared to control. No reduction was observed in AChE concentrations in soft
      tissues of both mollusks may due to that DHO was a non-neurotoxicant to Unio
      tigridis and Viviparous bengalensis. The results of DNA damage parameters were
      showed significant differences (p<= 0.05) between control and DHO concentrations
      except lowest concentration for each parameter measured in digestive gland of
      Unio tigridis. As well as, these significant differences were recorded between
      control and three concentrations of DHO exposure for comet length, and tail
      length parameters, and between control and highest oil concentration for tail
      moment in Viviparous bengalensis. DHO has the ability to prevent the reproduction
      of Viviparous bengalensis snail relation to control, that is what we considered
      strong evidence of the toxicity properties of DHO on the reproductive status of
      this species of snails. SOD, CAT, and MDA were useful biomarkers for evaluating
      the toxicity of DHO in mussel and snails, and comet assay was a good tool to
      assess the potential genotoxicity of DHO.

PMID- 29660616
TI  - Intestinal damage, neurotoxicity and biochemical responses caused by tris (2
      chloroethyl) phosphate and tricresyl phosphate on earthworm.
AB  - Organophosphate esters (OPEs) draw growing concern about characterizing the
      potential risk on environmental health due to its wide usage and distribution.
      Two typical types of organophosphate esters (OPEs): tris (2-chloroethyl)
      phosphate (TCEP) and tricresyl phosphate (TCP) were selected to evaluate toxicity
      of OPEs to the soil organism like earthworm (Eisenia fetida). Histopathological
      examination (H&E), oxidative stress, DNA damage and RT-qPCR was used to identify
      the effects and potential mechanism of their toxicity. Hameatoxylin and eosin
      (H&E) demonstrated that intestinal cells suffered serious damage, and the
      observed up-regulation of chitinase and cathepsin L in mRNA levels confirmed it.
      Both TCEP and TCP significantly increased the DNA damage when the concentrations
      exceeded 1 mg/kg (p < 0.01), and a dose-response relationship was observed. In
      addition, TCEP and TCP also changed the acetylcholinesterase (AChE) activity and
      expression of genes associated with neurotoxic effects in earthworms even under
      exposure to low OPEs concentration (0.1 mg/kg). Moreover, genes associated with
      nicotinic acetylcholine receptors (nAChR) and carrier protein further
      demonstrated that highest concentration of TCEP (10 mg/kg) may have an
      overloading impact on the cholinergic system of E. fetida. Integrated Biological
      Response index (IBRv2) showed that TCEP exerted stronger toxicity than TCP under
      the same concentrations. We deduced that the observed intestinal damage,
      oxidative stress and neurotoxic effect might be the primary mechanisms of TCEP
      and TCP toxicity. This study provides insight into the toxicological effects of
      OPEs on earthworm model, and may be useful for risk assessment of OPEs on soil
      ecosystems.

PMID- 29660617
TI  - Changes in bacterial community structure and antibiotic resistance genes in soil
      in the vicinity of a pharmaceutical factory.
AB  - China is the largest global producer of antibiotics. With the demand for
      antibiotics increasing every year, it is necessary to assess potential
      environmental risks and the spread of antibiotic resistance genes (ARGs)
      associated with antibiotic production. Here, we investigated the occurrence and
      distribution of ARGs in soil in the vicinity of a pharmaceutical factory. The
      results showed that antibiotic concentrations were under the detection limit;
      however, ARGs were present in soil and tended to be enriched near the factory. A
      significant correlation between the relative abundance of intI-1 and tetracycline
      ARGs implied that horizontal gene transfer might play an important role in the
      spread of ARGs. The occurrence of these ARGs could be the results of previous
      antibiotic contamination. However, the soil bacterial community structure seemed
      to be more affected by nutrients or other factors than by antibiotics. Overall,
      this study supports the viewpoint that long-term pharmaceutical activity might
      have a negative effect on environmental health, thus, underscoring the need to
      regulate antibiotic production and management.

PMID- 29660618
TI  - A detection method in living plant cells for rapidly monitoring the response of
      plants to exogenous lanthanum.
AB  - The pollution of rare earth elements (REEs) in ecosystem is becoming more and
      more serious, so it is urgent to establish methods for monitoring the pollution
      of REEs. Monitoring environmental pollution via the response of plants to
      pollutants has become the most stable and accurate method compared with
      traditional methods, but scientists still need to find the primary response of
      plants to pollutants to improve the sensitivity and speed of this method. Based
      on the facts that the initiation of endocytosis is the primary cellular response
      of the plant leaf cells to REEs and the detection of endocytosis is complex and
      expensive, we constructed a detection method in living plant cells for rapidly
      monitoring the response of plants to exogenous lanthanum [La(III), a
      representative of REEs] by designing a new immuno-electrochemical method for
      detecting the content change in extracellular vitronectin-like protein (VN) that
      are closely related to endocytosis. Results showed that when 30 MUM La(III)
      initiated a small amount of endocytosis, the content of extracellular VN
      increased by 5.46 times, but the structure and function of plasma membrane were
      not interfered by La(III); when 80 MUM La(III) strongly initiated a large amount
      of endocytosis, the content of extracellular VN increased by 119 times,
      meanwhile, the structure and function of plasma membrane were damaged. In
      summary, the detection method can reflect the response of plants to La(III) via
      detecting the content change in extracellular VN, which provides an effective and
      convenient way to monitor the response of plants to exogenous REEs.

PMID- 29660619
TI  - Highly efficient removal of nitrogen and phosphorus in an electrolysis-integrated
      horizontal subsurface-flow constructed wetland amended with biochar.
AB  - Electrolysis combined with biochar (BC) was used in a constructed wetland to
      intensify nitrogen (N) and phosphorus (P) removal from wastewater simultaneously.
      A pilot study was conducted using an electrolysis-integrated, BC-amended,
      horizontal, subsurface-flow, constructed wetland (E-BHFCW). The research results
      showed that both electrolysis and BC substrate played important roles in the
      intensified, constructed wetland. The electrolysis combined BC substrate greatly
      enhanced the removal rates of nitrate (49.54%) and P (74.25%) when the E-BHFCW
      operated under the lower current density of 0.02 mA/cm2 and an electrolysis time
      of 24 h. Improved N removal was accomplished with the electrochemical
      denitrification of iron cathodes; the autotrophic denitrification bacteria
      appeared to remove nitrate which was adsorbed on the BC substrate because
      hydrogen gas was produced by cathodes in the E-BHFCW. Less nitrate was taken
      directly by wetland plants and microbes. The in-situ formation of ferric ions
      from a sacrificial iron anode, causing P chemical sedimentation and physical
      adsorption, improved P removal. BC, modified by iron ions from an iron anode to
      adsorb the nitrate and P, was a good material to improve effluent water quality.
      It can also serve as a favorable microbial carrier to bio-transform nitrate to N
      gas. This is because there were abundant and diverse bacterial communities in the
      biofilm on the BC substrate in the E-BHFCW. Thus, electrolysis integrated with BC
      in a constructed wetland is a novel, feasible and effective technique for
      enhancing wastewater N and P removal.

PMID- 29660620
TI  - Using river sediments to analyze the driving force difference for non-point
      source pollution dynamics between two scales of watersheds.
AB  - The formation and transportation processes of non-point source (NPS) pollution
      varied among the studied watersheds in the Northeastern China, so we hypothesized
      that the driving force behind NPS pollution followed the spatial scale effect.
      With a watershed outlet sedimentary flux analysis and a distributed NPS pollution
      loading model, we investigated the temporal dynamics of NPS and the differences
      in driving forces. Sediment core samples were collected from two adjacent
      watersheds, the smaller Abujiao watershed and the larger Naoli watershed. The
      natural climatic conditions, long-term variations in the distribution of land
      use, soil properties and tillage practices were the same in the two watersheds.
      The vertical distributions of total nitrogen, total phosphorus, Zn and As at 1-cm
      intervals in the section showed clear differences between the watersheds. There
      were higher concentrations of total nitrogen and total phosphorus in the larger
      watershed, but the heavy metals were more concentrated in the smaller watershed.
      Lead-210 (210Pb) analyses and the constant rate of supply model provided a dated
      sedimentary flux, which was correlated with the corresponding yearly loading of
      NPS total nitrogen and total phosphorus in the two watersheds. The total
      phosphorus showed a stable relationship in both watersheds with an R2 value that
      ranged from 0.503 to 0.682. A rose figure comparison also demonstrated that the
      pollutant flux in the sediment was very different in the two watersheds, which
      had similar territorial conditions and different hydrological patterns.
      Redundancy analysis further indicated that expanding paddy areas had a large
      impact on the sedimentary flux of nitrogen and phosphorus in the smaller
      watershed, but precipitation had a direct impact on NPS loading in the larger
      watershed. We concluded that the spatial scale effect affected the NPS pollution
      via the transport processes in the waterway, which was mainly influenced by
      branch length and drainage density.

PMID- 29660621
TI  - Analysis and modelling of powdered activated carbon dosing for taste and odour
      removal.
AB  - A series of experiments were undertaken in order to understand and predict the
      dosage of powdered activated carbon required to remove taste and odour compounds
      in an Australian drinking water treatment plant. Competitive effects with organic
      matter removal by aluminium sulphate during coagulation were also quantified.
      Data on raw and finished water quality following jar tests, as well as chemical
      dosages and treatment performance, were statistically analysed, and a data-driven
      prediction model was developed. The developed powdered activated carbon dosage
      prediction model can be used by the plant operators for rapid dosage assessment
      and can increase the preparedness of the plant to sudden taste and odour events.
      It was also found that total organic carbon levels and properties greatly affect
      the ability of powdered activated carbon to remove taste and odour compounds; on
      the other hand, total organic carbon removal is not affected by high taste and
      odour levels, since these were still much lower than organic carbon
      concentrations.

PMID- 29660622
TI  - Wetting phenomena in membrane distillation: Mechanisms, reversal, and prevention.
AB  - Membrane distillation (MD) is a rapidly emerging water treatment technology;
      however, membrane pore wetting is a primary barrier to widespread industrial use
      of MD. The primary causes of membrane wetting are exceedance of liquid entry
      pressure and membrane fouling. Developments in membrane design and the use of
      pretreatment have provided significant advancement toward wetting prevention in
      membrane distillation, but further progress is needed. In this study, a broad
      review is carried out on wetting incidence in membrane distillation processes.
      Based on this perspective, the study describes the wetting mechanisms, wetting
      causes, and wetting detection methods, as well as hydrophobicity measurements of
      MD membranes. This review discusses current understanding and areas for future
      investigation on the influence of operating conditions, MD configuration, and
      membrane non-wettability characteristics on wetting phenomena. Additionally, the
      review highlights mathematical wetting models and several approaches to wetting
      control, such as membrane fabrication and modification, as well as techniques for
      membrane restoration in MD. The literature shows that inorganic scaling and
      organic fouling are the main causes of membrane wetting. The regeneration of
      wetting MD membranes is found to be challenging and the obtained results are
      usually not favorable. Several pretreatment processes are found to inhibit
      membrane wetting by removing the wetting agents from the feed solution. Various
      advanced membrane designs are considered to bring membrane surface non
      wettability to the states of superhydrophobicity and superomniphobicity; however,
      these methods commonly demand complex fabrication processes or high-specialized
      equipment. Recharging air in the feed to maintain protective air layers on the
      membrane surface has proven to be very effective to prevent wetting, but such
      techniques are immature and in need of significant research on design,
      optimization, and pilot-scale studies.

PMID- 29660623
TI  - Hydrothermal preparation of 3D flower-like BiPO4/Bi2WO6 microsphere with enhanced
      visible-light photocatalytic activity.
AB  - A novel 3D flower-like BiPO4/Bi2WO6 photocatalyst was prepared using hydrothermal
      method. The crystal structure, surface morphologies and optical properties of the
      samples were characterized by X-ray diffraction (XRD), scanning electron
      microscopy (SEM), energy dispersive spectroscopy (EDS), transmission electron
      microscopy (TEM), X-ray photoelectron spectroscopy (XPS), Brunauer-Emmett-Teller
      (BET) and Ultraviolet-visible diffuse reflectance spectrum (UV-vis DRS). The
      photocatalytic activity of the BiPO4/Bi2WO6 composites was evaluated by using
      rhodamine B (RhB) as a target organic pollutant under visible light irradiation.
      The composite with the content of 15% BiPO4 exhibited the highest photocatalytic
      property with the 92% removal rate of RhB within 100 min under visible light
      irradiation, which ascribed to the fast separation efficiency of photo-induced
      charge carriers, according with the results of photoluminescence (PL),
      photocurrent (PC) and electrochemical impedance spectroscopy (EIS). Also, it
      showed superior stability after three times of recycling. Eventually, the
      possible photocatalytic mechanism of BiPO4/Bi2WO6 composite was proposed
      according to the energy band structure and the radical-trapping experiment.

PMID- 29660624
TI  - High-response and low-temperature nitrogen dioxide gas sensor based on gold
      loaded mesoporous indium trioxide.
AB  - Nitrogen dioxide (NO2), as a typical threatening atmospheric pollutant, is
      hazardous to the environment and human health. Thus, the development of a gas
      sensor with high response and low detection limit for NO2 detection is highly
      important. The highly ordered mesoporous indium trioxide (In2O3) prepared by
      simple nanocasting method using mesoporous silica as template and decorated with
      Au nanoparticles was investigated for NO2 detection. The prepared materials were
      characterized by X-ray diffraction, transmission electron microscopy, and X-ray
      photoelectron spectroscopy. Characterization results showed that the samples
      exhibited ordered mesostructure and were successfully decorated with Au. The gas
      sensing performance of the sensors based on a series of Au-loaded mesoporous
      In2O3 were systematically investigated. The Au loading level strongly affected
      the sensing performance toward NO2. The optimal sensor, which was based on 0.5
      wt% Au-loaded In2O3, displayed high sensor response and low detection limit of 10
      ppb at low operating temperature of 65  degrees C. The excellent sensing
      properties were mainly attributed to the ordered mesoporous structure and the
      catalytic performance of Au. We believe that the Au-loaded mesoporous In2O3 can
      provide a promising platform for NO2 gas sensors with excellent performance.

PMID- 29660625
TI  - Construction of CdS@UIO-66-NH2 core-shell nanorods for enhanced photocatalytic
      activity with excellent photostability.
AB  - A novel class of CdS@UIO-66-NH2 core shell heterojunction was fabricated by the
      facile in-situ solvothermal method. Characterizations show that porous UIO-66-NH2
      shell not only allows the visible light to be absorbed on CdS nanorod core, but
      also provides abundant catalytic active sites as well as an intimate
      heterojunction interface between UIO-66-NH2 shell and CdS nanorod core. By taking
      advantage of this property, the core-shell composite presents highly solar-driven
      photocatalytic performance compared with pristine UIO-66-NH2 and CdS nanorod for
      the degradation of organic dyes including malachite green (MG) and methyl orange
      (MO), and displays superior photostability after four recycles. Furthermore, the
      photoelectrochemical performance of CdS@UIO-66-NH2 can be measured by the UV-vis
      spectra, Mott-Schottky plots and photocurrent. The remarkably enhanced
      photocatalytic activity of CdS@UIO-66-NH2 can be ascribed to high surface areas,
      intimate interaction on molecular scale and the formation of one-dimensional
      heterojunction with n-n type. What's more, the core-shell heterostructural
      CdS@UIO-66-NH2 can facilitate the effective separation and transfer of the
      photoinduced interfacial electron-hole pairs and protect CdS nanorod core from
      photocorrosion.

PMID- 29660626
TI  - Tubulin posttranslational modifications in in vitro matured prepubertal and adult
      ovine oocytes.
AB  - Microtubules (MTs), polymers of alpha/beta-tubulin heterodimers, are involved in
      crucial functions in eukaryotic cells. MTs physiology can be influenced by a
      variety of post-translational modifications (PTMs), including tyrosination,
      detyrosination, delta 2 modification, acetylation, polyglutamylation,
      polyglycylation. In mammalian oocytes, MTs are essential for meiosis, regulating
      the formation of meiotic spindle and chromosomes movements. Considering that the
      patterns of tubulin PTMs (tyrosination, detyrosination, acetylation,
      polyglutamylation and delta 2 modification) have not been investigated in ovine
      oocytes, this study has been designed to investigate their presence and
      quantification in in vitro matured (IVM) adult and prepubertal ovine oocytes.
      Oocytes from adult and lamb Sarda ewes, regularly slaughtered at the local
      abattoir, were in vitro matured, fixed, and processed by indirect
      immunofluorescence and confocal microscopy analyses at metaphase II stage. Our
      results revealed a well detectable signal for total, tyrosinated and acetylated
      alpha-tubulin in meiotic spindle of both sheep and lamb oocytes. On the other
      hand, no immunopositivity were appreciable for detyrosinated, polyglutamylated,
      and delta 2 tubulin in meiotic spindle of both sheep and lamb oocytes. As regard
      the tyrosinated and the acetylated alpha-tubulin PTMs, through the quantification
      of the fluorescence intensity, we did not find significant differences in their
      expression in meiotic spindle of sheep, while in lamb the acetylated tubulin
      levels were predominant in comparison with tyrosinated. Our results in addition
      to investigating for the first time the different tubulin PTMs in the spindle
      organization of ovine oocytes, showed a different microtubule pattern between
      adult and prepubertal oocytes. The microtubule cytoskeleton survey may thus
      suggest further cues to better understand skill-related problems in in the
      acquisition of oocyte competence.

PMID- 29660627
TI  - Positive effect of resveratrol against preantral follicles degeneration after
      ovarian tissue vitrification.
AB  - This study aimed to evaluate whether the addition of resveratrol to
      vitrification/thawing medium improves the cryotolerance of preantral follicles
      enclosed in bovine ovarian fragments. Ovarian fragments were obtained from bovine
      fetuses and distributed to the following groups: fresh ovarian fragments
      (control), vitrified (VIT), and vitrified with resveratrol (VIT + RESV). Overall,
      the mean percentage of normal follicles was greater (P < 0.05) in the VIT + RESV
      compared to the VIT group. Moreover, the probability of finding normal follicles
      was 2.5 greater (P < 0.05) in the VIT + RESV group. In class comparison, the
      primordial and transitional follicles have ~3.0 times (P < 0.05) greater odds of
      being normal after vitrification compared to the secondary follicles.
      Additionally, a negative association (P < 0.05) was observed between the
      proportion of viable follicles and the stage of follicular development. ROS
      levels were similar (P > 0.05) between the VIT and VIT + RESV groups, and both
      were lower (P < 0.05) than the control group. The tissue viability in the VIT +
      RESV group was similar (P > 0.05) to the control group. In summary, the
      resveratrol provided greater ovarian tissue viability and has a positive effect
      against degeneration of preantral follicles enclosed in ovarian fragments.

PMID- 29660628
TI  - Transcriptional abundance of type-1 endocannabinoid receptor (CB1) and fatty acid
      amide hydrolase (FAAH) in bull spermatozoa: Relationship with field fertility.
AB  - A highly sophisticated endogenous cannabinoid system (ECS) has been shown to play
      a crucial role in controlling sperm functions and fertility in men. In the
      present study, we report the differences in the expression level of components of
      ECS [type-1 endocannabinoid receptor (CB1) and fatty acid amide hydrolase (FAAH)]
      in spermatozoa from bulls with different field fertility ratings. Cryopreserved
      spermatozoa from crossbred cattle bulls (n = 40) were utilized for the study. The
      bulls were classified into high-, medium- and low-fertile bulls based on field
      conception rates. Sperm viability, capacitation status and protamine deficiency
      were assessed. Spermatozoa RNA was isolated from all the bulls, cDNA was
      synthesized and quantitative real time PCR was carried out to study the
      transcriptional abundance of CB1 and FAAH genes. Sperm viability was lower and
      capacitation was higher (p < 0.05) in low fertile bulls compared to medium and
      high fertile bulls. The expression level of CB1 gene was significantly (p < 0.05)
      lower in spermatozoa from low and medium fertile bulls compared to high fertile
      bulls. The expression of CB1 gene was 21.07 and 4.23 times greater in high and
      medium fertile bulls, respectively compared to low fertile bulls. The correlation
      between CB1 gene expression and field conception rate of bulls was positive and
      significant (r = 0.57; p < 0.001). Unlike CB1 receptors, FAAH gene expression was
      similar among high, medium and low fertile bulls. The correlation of FAAH
      expression with bull conception rate was positive but not significant. It was
      concluded that the transcriptional abundance of type-1 endocannabinoid receptor
      (CB1) was positively and significantly related to bull fertility.

PMID- 29660629
TI  - Fatty acid profile of blood plasma and oviduct and uterine fluid during early and
      late luteal phase in the horse.
AB  - During early pregnancy, the secretome of both oviduct and uterus serves as
      exchange medium for signaling factors between embryo and mother and provides the
      embryo with nutrients. The preimplantation embryo can utilize the fatty acids
      (FA) therein via direct incorporation into cell membrane lipid bilayers and for
      energy production via beta-oxidation. The FA concentration and composition of the
      oviduct (OF) and uterine fluid (UF) might be regulated by ovarian hormones to
      meet the changing needs of the growing embryo. In our study, we analyzed the FA
      profile of blood plasma (BP) and reproductive fluid samples obtained post mortem
      from slaughtered mares by gas chromatography mass spectrometry. Cycle stage was
      determined by visual evaluation of the ovary and measurement of plasma
      progesterone. No major effect of cycle stage on the FA profile was observed.
      However, the composition of FA was different between BP and both OF and UF. While
      linoleic, stearic, oleic and palmitic acid were the four most prevalent FA in
      both BP and reproductive fluids, the latter contained higher concentrations of
      arachidonic, eicosapentaenoic and dihomo-gamma-linolenic acid. The finding
      suggests selective endometrial transport mechanisms from plasma into the
      reproductive fluids or increased endometrial synthesis of selected FA.

PMID- 29660630
TI  - Anti-apoptotic effects of minocycline on ram epididymal spermatozoa exposed to
      oxidative stress.
AB  - Cryopreservation causes major damage to sperm cells and thereby, increased
      apoptosis has been documented as physiologically programmed cells death. The goal
      of current study was to evaluate the anti-apoptotic effects of minocycline
      compared to sericin added to diluents on frozen-thawed spermatozoa. Epididymal
      spermatozoa isolated from 50 pairs testes with motility >80% and total
      morphological abnormalities <10% were pooled, divided into 9 aliquots and used
      for cryopreservation. The semen samples were re-suspended with basic Tris egg
      yolk diluent containing minocycline (5 and 10 mg) and tert-butyl hydro peroxide
      (10 and 20 MUm) and sericin (0.5 gr). Total sperm motility and progressive
      motility were evaluated by Computed Assisted System Analysis (CASA). Acrosome and
      plasma integrity, viability, hypo osmotic swelling test, malondialdehyde
      concentration, DNA fragmentation test, mitochondrial activity, apoptotic
      features, caspase activity and level of H2O2 and O2 were assessed as completed
      characteristics of frozen-thawed spermatozoa. The results indicate that 10 mg
      minocycline added to extender resulted in significant (P < 0.05) enhancement of
      total motility, progressive motility and viability of post-thawing spermatozoa.
      The results of plasma membrane demonstrate significantly (P < 0.05) higher value
      of both minocycline concentrations with 10 MUm tert-butyl hydro peroxide. In
      regard to caspase activity, diluents supplemented with 5 and 10 mg minocycline
      improved significantly (P < 0.05) the rate of viable spermatozoa. The results of
      malondialdehyde concentration show diluents supplemented with 10 mg minocycline
      and 0.5 gr sericin were significantly (P < 0.05) lower than other extenders. The
      ratio of sperm chromatin dispersion stained spermatozoa illustrated the higher
      rate in extenders containing 10 mg minocycline plus 10 MUm tert-butyl hydro
      peroxide, 5 mg minocycline plus 10 MUm tert-butyl hydro peroxide and 5 and 10 mg
      minocycline were significantly (P < 0.05) than other treatments. Moreover, the
      results of mitochondrial activity show significantly (P < 0.05) an improvement by
      supplementation of 5 and 10 mg minocycline. Regarding the apoptosis occurrence
      and intracellular ROS, the results demonstrate significantly (P < 0.05) higher
      live post thawed spermatozoa and lowest value for diluents containing 10 and 5
      mg, respectively. In conclusion, the results indicate that addition of 10 mg
      minocycline seems to reduce the apoptotic marker during cryopreservation of
      epididymal ram spermatozoa.

PMID- 29660631
TI  - Using molecular dynamics for multislice TEM simulation of thermal diffuse
      scattering in AlGaN.
AB  - For simulation of transmission electron microscopic images and diffraction
      patterns, the accurate inclusion of thermal diffuse scattering by phonons is
      important. In the frozen phonon multislice algorithm, this is possible, if
      thermal displacements according to the realistic, quantum mechanical distribution
      can be generated. For pure crystals, quantum mechanical calculations based on DFT
      yield those displacements. But for alloys one is usually restricted to the
      Einstein approximation, where correlations between atoms are neglected. In this
      article, molecular dynamics simulations are discussed and used as an alternative
      method for displacement calculation. Employing an empirical Stillinger-Weber type
      potential, classical motion is used as an approximation for the quantum
      mechanical dynamics. Thereby, correlations and possible static atomic
      displacements are inherently included. An appropriate potential is devised for
      AlGaN by fitting to force constant matrices determined from DFT and elastic
      constants of AlN and GaN. A comparison shows that the empiric potential
      reproduces phonon dispersions and displacement expectations from DFT references.
      The validity for alloys is successfully demonstrated by comparison to DFT
      calculations in special quasirandom structures. Subsequently, molecular dynamics
      were used in multislice simulations of both conventional and scanning TEM images.
      The resulting images are in very good agreement with DFT based calculations,
      while a slight yet significant deviation from Einstein approximation results can
      be seen, which can be attributed to the neglect of correlations in the latter.
      The presented potential hence proves to be a useful tool for accurate TEM
      simulations of AlGaN alloys.

PMID- 29660632
TI  - Female PFP patients present alterations in eccentric muscle activity but not the
      temporal order of activation of the vastus lateralis muscle during the single leg
      triple hop test.
AB  - This study aimed to compare the concentric and eccentric activity and the
      temporal order of peak activity of the hip and knee muscles between women with
      patellofemoral pain (PFP) and healthy women during the single leg triple hop test
      (SLTHT). Electromyographic (EMG) and Kinematic data were collected from 14
      healthy women (CG) and 14 women diagnosed with PFP (PFG) during a single session
      of the single leg triple hop test. Integral surface electromyography (iEMG) data
      of the hip and knee muscles in eccentric and concentric phases and the length of
      time that each muscle needed to reach the maximal peak of muscle activity were
      calculated. The iEMG in the eccentric phase was significantly higher (p < 0.05)
      than the concentric phase, for the gluteus maximus and gluteus medius muscles (CG
      and PFG) and for the vastus lateralis muscle (PFG). The vastus lateralis muscle
      was the first muscle to reach the highest peak of activity in the PFG, and the
      third to reach this peak in the CG. In the present study, the activity of the
      vastus lateralis muscle during the eccentric phase of the jump was greater than
      concentric phase, as a temporal anticipation of its peak in activity among women
      with PFP.

PMID- 29660633
TI  - Objective assessment of gait and posture in premanifest and manifest Huntington
      disease - A multi-center study.
AB  - BACKGROUND: Deficits in posture and gait are known to contribute to the complex
      motor phenotype of Huntington disease (HD). Objective and quantitative measures
      of posture and gait provided by posturography and GAITRite(r) assessments may
      supplement categorical rating scales such as the UHDRS-TMS and increase power and
      sensitivity of clinical trials. OBJECTIVES: To investigate whether posturography
      and GAITRite(r) measures reveal (1) changes in manifest or premanifest HD
      mutation-carriers, (2) a correlation to the UHDRS-TMS and functional measures in
      manifest HD, and (3) a correlation to the disease-burden-score (based on CAG
      repeat-length and age). METHODS: Posturography and GAITRite(r) were applied in
      premanifest (n = 26) and manifest HD gene-mutation-carriers (n = 40) in different
      paradigms compared to age-matched controls (n = 30) in a cross-sectional multi
      site study conducted in three centers. Subjects were assessed clinically with the
      UHDRS Total-Motor-Score, Total-Functional-Capacity and Functional-Assessment
      Scale. RESULTS: Several posturography measures were able to discriminate between
      controls, premanifest, and manifest mutation-carriers in both conditions
      assessed. Only one GAITRite(r) measure separated controls and premanifest
      participants, while discrimination between controls and manifest same as between
      premanifest and manifest participants was possible in several measures.
      Correlation with all clinical measures was seen in only one measure per device
      while correlations to the disease-burden-score seen in posturography only.
      CONCLUSION: Overall the results suggests that posturography detects alterations
      in premanifest and manifest mutation-carriers more reliably than GAITRite(r)
      measures. Correlations with clinical assessment scores are limited; correlation
      with disease-burden-score is seen in posturography only. Data acquisition and
      analysis was easier with posturography than GAITRite(r) assessments in out
      patient settings.

PMID- 29660634
TI  - Comparison of osteointegration property between PEKK and PEEK: Effects of surface
      structure and chemistry.
AB  - Weak osteointegration affects the long-term stability of polyaryletherketone
      (PAEK) implants. Surface modification provides a potential solution to improve
      the osteointegration property of PAEKs. Polyetheretherketone (PEEK) and
      polyetherketoneketone (PEKK) are two representative PAEK materials, but the
      latter has more ketone groups and better potential for surface chemical
      modification than the former. In this work, porous PEKK (PEKK-P) and PEEK (PEEK
      P) were fabricated by a porogen leaching method. The samples were treated with
      80% sulfuric acid (PEKK-SP and PEEK-SP) and then simulated body fluid (SBF)
      incubation (PEKK-BSP and PEEK-BSP). More micropores and higher hydrophilic SO3H
      groups were found on PEKK-SP than PEEK-SP. Likely, more bone-like apatite
      crystals deposited on PEKK-BSP than PEEK-BSP. To evaluate their osteointegration
      properties, the samples were implanted in femoral condyle defects (Phi3 * 4 mm3)
      of rat models, and micro-computed tomography (MU-CT), histology and mechanical
      analyzes were performed on the retrieved specimens. For control groups, i.e. the
      dense samples (PEKK-D and PEEK-D), only a handful of bone creeping growth on the
      implant surface was seen on them. However, with the interconnected macropores,
      surface micro/nano topography and bone-like apatite, notable bone growth into the
      inner pores was observed on PEKK-BSP and PEEK-BSP. Furthermore, quantitative
      analyses confirmed that the newly formed bone in PEKK-BSP was nearly more than
      doubled than that in PEEK-BSP. The push-out force testing results (PEKK-D ~ PEEK
      D < PEKK-P ~ PEEK-P < PEEK-BSP < PEKK-BSP) suggested that the surface chemical
      modification (sulfonation treatment followed by SBF incubation) along with build
      in porous structure played more important role in enhancing the mechanical
      stability of both PAEK materials than just the physical structure change. Our
      results revealed that PEKK with more ketone groups allowed easier sulfonation and
      better bone-like apatite deposition than PEEK, thus endowing PEKK-BSP with better
      osteointegration and mechanical stability than PEEK-BSP. Therefore, surface
      modified PEKK could be potential candidate for spinal and orthopedic applications
      requiring good osteointegration property.

PMID- 29660635
TI  - Caffeine-catalyzed gels.
AB  - Covalently cross-linked gels are utilized in a broad range of biomedical
      applications though their synthesis often compromises easy implementation. Cross
      linking reactions commonly utilize catalysts or conditions that can damage
      biologics and sensitive compounds, producing materials that require extensive
      post processing to achieve acceptable biocompatibility. As an alternative, we
      report a batch synthesis platform to produce covalently cross-linked materials
      appropriate for direct biomedical application enabled by green chemistry and
      commonly available food grade ingredients. Using caffeine, a mild base, to
      catalyze anhydrous carboxylate ring-opening of diglycidyl-ether functionalized
      monomers with citric acid as a tri-functional crosslinking agent we introduce a
      novel poly(ester-ether) gel synthesis platform. We demonstrate that biocompatible
      Caffeine Catalyzed Gels (CCGs) exhibit dynamic physical, chemical, and mechanical
      properties, which can be tailored in shape, surface texture, solvent response,
      cargo release, shear and tensile strength, among other potential attributes. The
      demonstrated versatility, low cost and facile synthesis of these CCGs renders
      them appropriate for a broad range of customized engineering applications
      including drug delivery constructs, tissue engineering scaffolds, and medical
      devices.

PMID- 29660636
TI  - Regional homogeneity and functional connectivity patterns in major depressive
      disorder, cognitive vulnerability to depression and healthy subjects.
AB  - BACKGROUND: Cognitive vulnerability to depression (CVD) is a high risk for
      depressive disorder. Recent studies focus on individuals with CVD to determine
      the neural basis of major depressive disorder (MDD) neuropathology. However,
      whether CVD showed specific or similar brain functional activity and connectivity
      patterns, compared to MDD, remain largely unknown. METHODS: Here, using resting
      state functional magnetic resonance imaging in subjects with CVD, healthy
      controls (HC) and MDD, regional homogeneity (ReHo) and resting-state functional
      connectivity (R-FC) analyses were conducted to assess local synchronization and
      changes in functional connectivity patterns. RESULTS: Significant ReHo
      differences were found in right posterior lobe of cerebellum (PLC), left lingual
      gyrus (LG) and precuneus. Compared to HC, CVD subjects showed increased ReHo in
      the PLC, which was similar to the difference found between MDD and HC. Compared
      to MDD patients, CVD subjects showed decreased ReHo in PLC, LG, and precuneus. R
      FC analyses found increased functional connections between LG and left inferior
      parietal lobule, posterior cingulate cortex, and dorsolateral prefrontal cortex
      in CVD compared to both HC and MDD. Moreover, Regional mean ReHo values were
      positively correlated with Center for Epidemiologic Studies Depression Scale
      scores. CONCLUSION: These analyses revealed that PLC and functional connections
      between LG and left inferior parietal lobule, posterior cingulate cortex, and
      dorsolateral prefrontal cortex may be a potential marker for CVD.

PMID- 29660637
TI  - Does oral administration of ketamine accelerate response to treatment in major
      depressive disorder? Results of a double-blind controlled trial.
AB  - BACKGROUND: Major depressive disorder (MDD) exerts a high health and financial
      burden on society. The conventional pharmacotherapies for MDD are partially
      effective and the response to medication often starts with some delay. There are
      recent reports of antidepressant effects for oral ketamine. METHODS: We employed
      a double-blind controlled trial to examine the time course of the therapeutic
      effect of ketamine when combined with the conventional administration of
      sertraline. A total of 81 patients participated in the study and were scored with
      the Hamilton Depression Rating Scale (HDRS) at baseline and at 2, 4 and 6 weeks
      after the start of the trial RESULTS: General linear model repeated measures
      demonstrated significant effect for time * treatment interaction on the HDRS
      scores, with significant difference at all time points post treatment. Early
      improvement was significantly greater in the ketamine group (85.4%) compared to
      the placebo group (42.5%). We did not observe any side effects for ketamine
      administration. LIMITATIONS: Our follow up was limited to 6 weeks post initiation
      of treatment and cannot reveal the potential long-term adverse effects of oral
      ketamine and the sustainability of its benefit. CONCLUSION: Altogether, our
      results suggest that oral ketamine may be considered as suitable adjuvant to
      sertraline in relieving depressive symptoms.

PMID- 29660638
TI  - Heterogeneity of sleep quality in relation to circadian preferences and
      depressive symptomatology among major depressive patients.
AB  - BACKGROUND: The current study aimed at investigating the latent dimensional
      structure of sleep quality as indexed by the seven components of the Pittsburgh
      Sleep Quality Index (PSQI), as well as latent covariance structure between sleep
      quality, circadian preferences and depressive symptoms. METHODS: Two hundred
      twenty-five patients with major depressive disorder (MDD), with an average age of
      29.92 +/- 10.49 years (aged between 17 and 63), participated in the study. The
      PSQI, Morningness-Eveningness Questionnaire (MEQ) and Beck Depression Inventory
      (BDI) were administered to participants. Four sets of latent class analyses were
      subsequently run to obtain optimal number of latent classes best fit to the data.
      RESULTS: Mixture models revealed that sleep quality is multifaceted in MDD. The
      data best fit to four-latent-class model: Poor Habitual Sleep Quality (PHSQ),
      Poor Subjective Sleep Quality (PSSQ), Intermediate Sleep Quality (ISQ), and Good
      Sleep Quality (GSQ). MDD patients classified into GSQ latent class (23.6%)
      reported the lowest depressive symptoms and were more prone to morningness
      diurnal preferences compared to other three homogenous sub-groups. Finally, the
      significant association between eveningness diurnal preferences and depressive
      symptomatology was significantly mediated by poor sleep quality. LIMITATION: The
      cross-sectional nature of the study and the lack of an objective measurement of
      sleep such as polysomnography recordings was the most striking limitation of the
      study. CONCLUSIONS: We concluded sleep quality in relation to circadian
      preferences and depressive symptoms has a heterogeneous nature in MDD.

PMID- 29660639
TI  - Elevated tumor necrosis factor-alpha receptor subtype 1 and the association with
      abnormal brain function in treatment-resistant depression.
AB  - BACKGROUND: Major depressive disorder (MDD) patients have shown elevated plasma
      levels of pro-inflammatory biomarkers compared to healthy controls. We
      hypothesized increased serum tumor necrosis factor-alpha receptor subtype 1 (TNF
      alpha R1) is more associated with impaired brain function in patients with
      treatment-resistant depression (TRD) than those without TRD. METHODS: 34 MDD
      patients and 34 healthy subjects were recruited and we separated MDD patients to
      TRD group (n = 20) and non-TRD (n = 14) group. Pro-inflammatory cytokines were
      assessed by enzyme-linked immunosorbent assays. A standardized uptake values
      (SUV) of glucose metabolism measured by 18F-FDG positron-emission-tomography
      (PET) was applied to all subjects for subsequent region-of- interest analyses and
      whole-brain voxel-wise analyses. 18F-FDG-PET measures glucose uptake into
      astrocytes in response to glutamate release from neuronal cells, and was thus
      used as a proxy measure to quantify glutamatergic neurotransmission in the human
      brain. RESULTS: Post-hoc analysis revealed that TRD group had higher serum
      concentrations of TNF-alpha R1 compared to healthy control or non-TRD group. In
      the MDD group, higher serum concentrations of TNF-alpha R1 significantly
      correlated with decreased SUV in anterior cingulate cortex (ACC) and bilateral
      caudate nucleus. The ROI analysis further supported the negative correlations of
      plasma TNF-alpha R1 and SUV in the ACC and caudate nucleus. Such correlation is
      more consistent in TRD group than in non-TRD and HC groups. LIMITATION: Glutamate
      neurotransmission and the effect of chronic stress on glutamate release in the
      brain were not measured directly. CONCLUSIONS: Increased TNF-alpha R1 was
      associated with impaired glutamatergic neurotransmission of caudate nucleus and
      ACC in MDD patients, particularly in the TRD.

PMID- 29660640
TI  - Parity and bipolar disorder: Additional considerations.

PMID- 29660641
TI  - Improvement of postpartum depression and psychosis after electroconvulsive
      therapy: A population-based study with a matched comparison group.
AB  - INTRODUCTION: Electroconvulsive therapy (ECT) is used to treat postpartum
      depression and psychosis based on clinical experience and small observational
      studies. AIMS: The primary aim was to test the hypothesis that the response rate
      to ECT for depression and psychosis is higher during the postpartum period than
      outside this period. The secondary aim was to identify predictors of a response
      to ECT during the postpartum period. MATERIALS AND METHODS: Cases with postpartum
      depression and/or psychosis received ECT within 6 months of delivery. A matched
      comparison group with depression and/or psychosis (not within the postpartum
      period) was identified from the Swedish National Quality Register for ECT. The
      improvement 1 week after ECT was classified according to the Clinical Global
      Impressions Scale - Improvement scale (CGI-I) as responder (CGI-I score 1-2) or
      non-responder (CGI-I score 3-7). RESULTS: 185 cases and 185 comparison group
      subjects were included (46% with psychosis in each groups). More cases (87.0%)
      than comparison group subjects (73.5%) responded to ECT (p = 0.001). Adjusted
      binary regression analysis revealed that more severe symptoms prior to treatment
      were the only statistically significant predictor of response. LIMITATIONS: There
      was no control group without ECT treatment. CONCLUSION: The response rate of
      those with postpartum depression and/or psychosis to ECT was high. The response
      rate of patients with psychosis or depression was higher during the postpartum
      period than outside it. This study supports the use of ECT for severe forms of
      postpartum depression and/or psychosis.

PMID- 29660642
TI  - Mindfulness-based interventions and their effects on emotional clarity: A
      systematic review and meta-analysis.
AB  - BACKGROUND: An inability to identify or describe internal emotional experience
      has been linked to a range of affective disorders. Despite burgeoning research on
      mindfulness-based interventions and their possible effects on emotion regulation,
      the effects of such interventions on emotional clarity is unclear. This review
      examines the evidence for the effect of mindfulness-based interventions on self
      reported emotional clarity. METHOD: Published studies indexed by PsycINFO, PubMed
      and Scopus, as available in April 2017, were systematically reviewed.
      Interventions that included mindfulness practice or philosophy, and reported a
      suitable measure of emotional clarity at pre- and post-intervention were
      selected. A random-effects meta-analysis was performed. Subgroup comparisons were
      also conducted to test for differences between clinical and non-clinical samples,
      between specific and approximate measures of emotional clarity, and between
      controlled and uncontrolled trials. RESULTS: Seventeen studies met the criteria
      for inclusion. The overall estimated effect size for pre- to post-intervention
      was small to moderate, Hedges' g = 0.42, 95% CI [0.25, 0.59] and for between
      groups results was small to large, Hedges' g = 0.52, 95% CI [0.15, 0.90].
      LIMITATIONS: Studies varied substantially in design quality and study
      characteristics. Furthermore, while interventions in the reviewed studies all had
      mindfulness components, many had other components in addition to mindfulness.
      Consequently, this review is limited by the heterogeneity of studies and results
      should be interpreted with caution. CONCLUSIONS: There is preliminary evidence to
      suggest that mindfulness-based interventions may increase emotional clarity.
      However, more homogenous and targeted experiments are required to confirm these
      initial findings.

PMID- 29660643
TI  - Gender-specific associations of depression and anxiety symptoms with mental
      rotation.
AB  - BACKGROUND: Men score higher on mental rotation tasks compared to women and
      suffer from depression and anxiety at half the rate of women. The objective of
      this study was to confirm the gender-specific effects of depression and anxiety
      on mental rotation performance. METHODS: We collected data in non-experimental
      conditions from 325 university students at three universities. Participants
      completed rating scales of depressive and anxiety symptoms, and then
      simultaneously performed a mental rotation task using tablet devices. RESULTS: We
      observed no significant difference between men and women in the depressive and
      anxiety symptoms and task response time. Men had a significantly higher correct
      answer rate compared with women. The scores of depression and anxiety of all
      participants were positively correlated. Task response time correlated positively
      with intensity of depressive symptoms and anxiety in women, but not in men. Women
      with high depressive symptoms had significantly longer response times than did
      women with low depressive symptoms, while men had no differences due to
      depressive symptoms. LIMITATIONS: We did not directly examine brain functions;
      therefore, the underlying neurobiological results are only based on previous
      knowledge and action data. CONCLUSIONS: The pathology of depression and anxiety
      was reflected in the correct answer rate and response time in relation to the
      gender difference of brain function used in mental rotation.

PMID- 29660644
TI  - Scared and surrounded by clutter: The influence of emotional reactivity.
AB  - BACKGROUND: Home visits can improve treatment outcomes for hoarding disorder, but
      factors influencing the success of home visits remain unknown. As home visits
      expose individuals to clutter and fear, the present study examined the effect
      that fear and emotional reactivity have on the relationship between clutter and
      discarding behaviour. METHODS: Participants with at least subclinical discarding
      problems (n = 143) were asked to save or discard personal possessions of varying
      value following an emotional induction that took place in either a tidy or
      cluttered context. Participants also completed questionnaires assessing hoarding
      severity, emotional state, and emotional reactivity, as defined by one's
      sensitivity, persistence, and intensity of reactions to emotional stimuli.
      RESULTS: As expected, participants discarded more items in the presence of
      clutter and when feeling fearful. However, emotional reactivity moderated the
      relations between environmental context, acute emotional state, and discarding.
      Low sensitivity, low persistence, and high emotional intensity negatively
      influenced discarding in the cluttered context. When feeling fearful, low
      dispositional emotional intensity negatively influenced discarding in the tidy
      context. LIMITATIONS: Individuals in the tidy environment reported higher levels
      of fear and anxiety than individuals in the cluttered environment after the fear
      induction. These differences could have contributed to the difference noted
      between the two contexts when examining the effect of emotional intensity
      tendencies. CONCLUSIONS: Providing treatment in an environment more
      representative of the cluttered home can improve discarding or at the very least
      give therapists a more accurate picture of what clients do in the context that
      matters most.

PMID- 29660645
TI  - The association between severity of depression and prescription opioid misuse
      among chronic pain patients with and without anxiety: A cross-sectional study.
AB  - BACKGROUND: In light of the increased rates of Prescription Opioid (PO) misuse
      and associated mortality in several developed countries in recent years, efforts
      have been made to identify populations who may be at increased risk for misuse of
      POs. Though the association between depression and PO misuse among pain patients
      is well documented, little is known regarding the effects of severity of
      depression on rates of misuse. In this study we explored rates of PO misuse among
      chronic pain patients screening positive for depression according to level of
      severity. METHODS: Participants included chronic pain patients receiving POs (N =
      554). All participants were screened for depression using the Patient Health
      Questionnaire (PHQ-9; cut-off scores of 5, 10, 15, and 20 for mild, moderate,
      moderate-severe and severe depression, respectively) and for opioid misuse using
      the Current Opioid Misuse Measure (COMM). Logistic regression analyses
      controlling for additional sociodemographic and clinical factors were conducted.
      RESULTS: Participants who screened positive for depression were at significantly
      increased odds to screen positive for opioid misuse (Adjusted Odds Ratio (AOR) =
      3.63; 95% Confidence Interval (CI) = 1.71-7.7) compared to those without
      depression. Severity of depression was significantly associated with increased
      odds for opioid misuse for moderate (AOR = 3.71; 95% CI = 1.01-13.76), moderate
      severe (AOR = 6.28; 95% CI = 1.6-24.57) and severe (AOR = 14.66; 95% CI = 3.28
      65.52) depression but not among those who screened positive for mild depression
      (AOR = 1.49; 95% CI = 0.39-5.68). LIMITATIONS: Cross-sectional study.
      CONCLUSIONS: Our results highlight the need to properly asses and address level
      of severity of co-morbid depression among chronic pain patients receiving POs.

PMID- 29660646
TI  - Trajectories of posttraumatic stress disorders among adolescents in the area
      worst-hit by the Wenchuan earthquake.
AB  - BACKGROUND: This study examined the trajectories of posttraumatic stress disorder
      (PTSD) among adolescents in the area worst-hit by the Wenchuan earthquake, and
      assessed the role of trauma exposure in differentiating distinct PTSD
      trajectories. METHODS: In total, 391 adolescents were selected from the Wenchuan
      and Maoxian counties in Sichuan province (the area worst-hit by the earthquake).
      Participants completed a trauma exposure questionnaire at 1 year, and the Child
      PTSD Symptom Scale at 1 year, 1.5 years, 2 years, and 2.5 years after the
      earthquake. RESULTS: Three latent PTSD trajectories were found in adolescents:
      moderate-stable (81.6%), decreasing (8.7%), and increasing trajectories (9.7%).
      T1 trauma exposure was more likely to be related to the decreasing trajectory
      group. LIMITATIONS: All variables were measured by self-report scales. There was
      high non-random dropout. CONCLUSION: The course of PTSD was heterogeneous among
      adolescents following the same natural disaster.

PMID- 29660647
TI  - Development of an adaptive electroporation system for intratumoral plasmid DNA
      delivery.
AB  - Intratumoral electroporation of plasmid DNA encoding the proinflammatory cytokine
      interleukin 12 promotes innate and adaptive immune responses correlating with
      anti-tumor effects. Clinical electroporation conditions are fixed parameters
      optimized in preclinical tumors, which consist of cells implanted into skin.
      These conditions have little translatability to clinically relevant tumors, as
      implanted models cannot capture the heterogeneity encountered in genetically
      engineered mouse models or clinical tumors. Variables affecting treatment outcome
      include tumor size, degree of vascularization, fibrosis, and necrosis, which can
      result in suboptimal gene transfer and variable therapeutic outcomes. To address
      this, a feedback controlled electroporation generator was developed, which is
      capable of assessing the electrochemical properties of tissue in real time.
      Determination of these properties is accomplished by impedance spectroscopy and
      equivalent circuit model parameter estimation. Model parameters that estimate
      electrical properties of cell membranes are used to adjust electroporation
      parameters for each applied pulse. Studies performed in syngeneic colon carcinoma
      tumors (MC38) and spontaneous mammary tumors (MMTV-PyVT) demonstrated feedback
      based electroporation is capable of achieving maximum expression of reporter
      genes with significantly less variability and applied energy. These findings
      represent an advancement to the practice of gene electro-transfer, as reducing
      variability and retaining transfected cell viability is paramount to treatment
      success.

PMID- 29660648
TI  - Gold nanoparticle-decorated reduced-graphene oxide targeting anti hepatitis B
      virus core antigen.
AB  - Hepatitis B virus core antigen (HBcAg) is the major structural protein of
      hepatitis B virus (HBV). The presence of anti-HBcAg antibody in a blood serum
      indicates that a person has been exposed to HBV. This study demonstrated that the
      immobilization of HBcAg onto the gold nanoparticles-decorated reduced graphene
      oxide (rGO-en-AuNPs) nanocomposite could be used as an antigen-functionalized
      surface to sense the presence of anti-HBcAg. The modified rGO-en-AuNPs/HBcAg was
      then allowed to undergo impedimetric detection of anti-HBcAg with anti-estradiol
      antibody and bovine serum albumin as the interferences. Upon successful detection
      of anti-HBcAg in spiked buffer samples, impedimetric detection of the antibody
      was then further carried out in spiked human serum samples. The electrochemical
      response showed a linear relationship between electron transfer resistance and
      the concentration of anti-HBcAg ranging from 3.91ngmL-1 to 125.00ngmL-1 with
      lowest limit of detection (LOD) of 3.80ngmL-1 at 3sigmam-1. This established
      method exhibits potential as a fast and convenient way to detect anti-HBcAg.

PMID- 29660649
TI  - Tribological evaluation of biomedical polycarbonate urethanes against articular
      cartilage.
AB  - This research investigated the in-vitro wear and friction performance of
      polycarbonate urethane (PCU) 80A as they interact with articular cartilage, using
      a customised multidirectional pin-on-plate tester. Condyles were articulated
      against PCU 80A discs (Bionate(r) I and Bionate(r) II) (configuration 1) and the
      results arising from these tests were compared to those recorded during the
      sliding of PCU pins against cartilage plates (configuration 2). Configuration 1
      produced steadily increasing coefficient of friction (COF) (up to 0.64 +/- 0.05)
      and had the same trend as the cartilage-on-stainless steel articulation (positive
      control). When synovial fluid rather than bovine calf serum was used as
      lubricant, average COF significantly decreased from 0.50 +/- 0.02-0.38 +/- 0.06
      for condyle-on-Bionate(r) I (80AI) and from 0.41 +/- 0.02-0.24 +/- 0.04 for
      condyle-on-Bionate(r) II (80AII) test configurations (p < 0.05). After 15 h
      testing, the cartilage-on-cartilage articulation (negative control) tests showed
      no cartilage degeneration. However, different levels of cartilage volume loss
      were found on the condyles from the positive control (12.5 +/- 4.2 mm3) and the
      PCUs (20.1 +/- 3.6 mm3 for 80 AI and 19.0 +/- 2.3 mm3 for 80AII) (p > 0.05). A
      good correlation (R2 =0.84) was found between the levels of average COF and the
      volume of cartilage lost during testing; increasing wear was found at higher
      levels of COF. Configuration 2 showed low and constant COF values (0.04 +/-
      0.01), which were closer to the negative control (0.03 +/- 0.01) and
      significantly lower than configuration 1 (p < 0.05). The investigation showed
      that PCU is a good candidate for use in hemiarthroplasty components, where only
      one of the two articulating surfaces is replaced, as long as the synthetic
      material is implanted in a region where migrating cartilage contact is achieved.
      Bionate(r) II showed better tribological performance, which suggests it is more
      favourable for use in hemiarthroplasty design.

PMID- 29660650
TI  - Evidence for gastroprotective, anti-inflammatory and antioxidant potential of
      methanolic extract of Cordia dichotoma leaves on indomethacin and stress induced
      gastric lesions in Wistar rats.
AB  - The Cordia dichotoma (CD) is having anticancer and other pharmacological effects
      as it contains mainly flavonoids. The present study was aimed to demonstrate the
      gastroprotective effect of methanolic extract of CD leaves (MECD) obtained using
      Soxhlet extractor. In this study the qualitative phytochemical analysis of MECD
      revealed the presence of bioflavonoids and determination of quercetin was
      confirmed by HPLC analysis. The MECD was administered orally at doses 50 mg/kg,
      100 mg/kg and 200 mg/kg against indomethacin induced gastric ulceration and
      stress-induced gastric ulceration in Wistar rats. Omeprazole at 10 mg/kg orally
      was used as the reference standard. The various parameters like gastric volume,
      gastric pH, total acidity, ulcer index, percent protection were estimated for
      assessment of anti-secretory and gastroprotective effects of MECD. At the same
      time antioxidant parameters like superoxide dismutase (SOD), catalase (CAT) and
      malondialdehyde (MDA) in addition to that inflammatory parameters such as tumor
      necrosis factor-alpha (TNF-alpha), interleukin-6 and interleukin-10 were also
      estimated according to their respective method of estimation using analyzing kit.
      The MECD have reduced gastric volume, total acidity and gastric mucosal damage in
      both the experimental models significantly and dose dependently as compared with
      control group. Similarly the antioxidant enzymes like SOD and CAT were increased
      while MDA levels were decreased significantly, at the same time TNF-alpha and IL
      6 levels were decreased and anti-inflammatory IL-10 levels were increased
      significantly in MECD treated groups. Thus the pretreatment with MECD has shown
      significant gastroprotective potential probably due to its antioxidant and anti
      inflammatory properties.

PMID- 29660651
TI  - Ecological and social patterns of child dietary diversity in India: a population
      based study.
AB  - OBJECTIVE: Dietary diversity (DD) measures dietary variation in children. Factors
      at the child, community, and state levels may be associated with poor child
      nutritional outcomes. However, few studies have examined the role of macro-level
      factors on child DD. This study seeks to 1) describe the distribution of child DD
      in India, 2) examine the variation in DD attributable to the child, community and
      state levels, and 3) explore the relationship between community socioeconomic
      context and child DD. RESEARCH METHODS AND PROCEDURES: Using nationally
      representative data from children aged 6-23 months in India, multilevel models
      were used to determine the associations between child DD and individual- and
      community-level factors. RESULTS: There was substantial variation in child DD
      score across demographic and socioeconomic characteristics. In an age and sex
      only adjusted regression model, the largest portion of variation in child DD was
      attributable to the child level (75%) while the portions of variance attributable
      to the community-level and state level were similar to each other (15% and 11%).
      Including individual-level socioeconomic factors explained 35.6 percent of the
      total variation attributed to child DD at the community level and 24.8 percent of
      the total variation attributed to child DD at the state level. Finally, measures
      of community disadvantage were associated with child DD in when added to the
      fully adjusted model. CONCLUSIONS: This study suggests that both individual and
      contextual factors are associated with child DD. These results suggest that a
      population-based approach combined with a targeted intervention for at-risk
      children may be needed to improve child DD in India.

PMID- 29660652
TI  - Cross-talk connections underlying dorsal and ventral stream integration during
      hand actions.
AB  - According to the dual-stream theory, the processing of visual information is
      divided into a ventral pathway mediating object recognition, and a dorsal pathway
      supporting visuomotor control. Increasing evidence suggests that these streams
      are not independent, but where this dorsal-ventral stream integration occurs
      remains unknown. We explored the candidate white matter pathways linking dorsal
      and ventral visual streams in 30 right-handed participants performing object
      oriented hand movements of varying complexity (reaching, grasping and lifting),
      using advanced diffusion imaging tractography based on the spherical
      deconvolution and kinematical analysis. We provided for the first time a direct
      evidence of cross-communication between dorsal and ventral visual streams in
      humans, through vertical occipital fasciculus and temporo-parietal fibers of the
      arcuate fasciculus during on-line control of grasping and lifting actions. We
      showed that individual differences in the microstructure of these cross-talk
      connections were associated with the variability of the arm deceleration, the
      grip opening and the grasp accuracy. This study suggests that hand kinematics, in
      skilled hand actions where high degree of online control is required, is related
      to the anatomy of the cross-talk networks between dorsal and ventral streams,
      bringing important insights to the dual-stream theory and the sensorimotor
      organization of hand actions.

PMID- 29660653
TI  - Antinociception induced by rosuvastatin in murine neuropathic pain.
AB  - BACKGROUND: Neuropathic pain, and subsequent hypernociception, can be induced in
      mice by paclitaxel (PTX) administration and partial sciatic nerve ligation
      (PSNL). Its pharmacotherapy has been a clinical challenge, due to a lack of
      effective treatment. In two models of mouse neuropathic pain (PTX and PSNL) the
      antinociception induced by rosuvastatin and the participation of proinflammatory
      biomarkers, interleukin (IL)- 1beta, TBARS and glutathione were evaluated.
      METHODS: A dose-response curve for rosuvastatin ip was obtained on cold plate,
      hot plate and Von Frey assays. Changes on spinal cord levels of IL-1beta,
      glutathione and lipid peroxidation were measured at 7 and 14days in PTX and PSNL
      murine models. RESULTS: PTX or PSNL were able to induce in mice peripheral
      neuropathy with hypernociception, either to 7 and 14days. Rosuvastatin induced a
      dose dependent antinociception in hot plate, cold plate and Von Frey assays. The
      increased levels of IL-1beta or TBARS induced by pretreatment with PTX or PSNL
      were reduced by rosuvastatin. The reduction of spinal cord glutathione, by PTX or
      PSNL, expressed as the ratio GSH/GSSG, were increased significantly in animals
      pretreated with rosuvastatin. The anti-inflammatory properties of statins could
      underlie their beneficial effects on neuropathic pain by reduction of
      proinflammatory biomarkers and activation of glia. CONCLUSION: The findings of
      this study suggest a potential usefulness of rosuvastatin in the treatment of
      neuropathic pain.

PMID- 29660654
TI  - Assessment of the possible roles of SB-269970 versus ketanserin on carbon
      tetrachloride-induced liver fibrosis in rats: Oxidative stress/TGF-beta1-induced
      HSCs activation pathway.
AB  - BACKGROUND: In liver fibrosis, a major morbid and mortal disease, oxidative
      stress motivation of hepatic stellate cells (HSCs)-into myofibroblasts terminated
      in collagen deposition remain the key pathophysiological deal. Serotonin (5-HT)
      through its HSCs-expressed receptors, especially 5-HT2A and 7, shows crucial
      events in fibrogenesis of chronic liver diseases. Molecular hepatic oxidative
      stress-fibrotic roles of 5-HT2A and 7 receptors antagonists (ketanserin and SB
      269970 respectively) are still a challenging issue. METHODS: Seven groups of
      adult male Wistar rats (n=10) were used. A carbon tetrachloride (CCl4) solution
      was injected intraperitoneally twice weekly for 6 weeks. On the 7th week, rats
      developed liver fibrosis were treated either by ketanserin (1mg/kg/day, ip) or SB
      269970 (2mg/kg/day, ip) for 14days. Survival rates, and serum alanine
      aminotransferase (ALT) and aspartate aminotransferase (AST) levels in addition to
      hepatic malondialdehyde (MDA) and reduced glutathione (GSH) levels, superoxide
      dismutase (SOD) and catalase (CAT) activities, and transforming growth factor
      beta1 (TGF-beta1) and procollagen type I N-terminal propeptide (PINP) levels,
      beside the hepatic histopathological fibrotic changes, were evaluated. RESULTS:
      In CCl4-challenged rats, each therapeutic approach showed significant reductions
      in elevated serum ALT, and AST levels, hepatic MDA, TGF-beta1, and PINP levels,
      and histopathological hepatic fibrotic scores as well as significant elevations
      in survival rates, reduced hepatic GSH levels, and SOD, and CAT activities.
      Remarkably, significant ameliorative measurements were observed in SB-269970
      treated group. CONCLUSION: Blockade of 5-HT2A and 7 receptors each alone could be
      a future reliable therapeutic approach in liver fibrosis through a reduction in
      oxidative stress/TGF-beta1-induced HSCs activation pathway.

PMID- 29660655
TI  - Urolithin A shows anti-atherosclerotic activity via activation of class B
      scavenger receptor and activation of Nef2 signaling pathway.
AB  - BACKGROUND: This study investigates the therapeutic potential of urothelin A in
      attenuating atherosclerotic lesion in wistar rat models and explore the role of
      Scavenger receptor-class B type I (SR-BI) and activation of Nrf-2 singling
      pathway. METHODS: Wistar rats (n=48) were feed with high cholesterol diet
      supplemented with Vitamin D3 and subjected to balloon injury of the aorta. Three
      days prior to the aortal injury, rats (n=16) were administered urothelin A
      (3mg/kg/d; po). Positive control were rats receiving high cholesterol diet and
      balloon injury of the aorta (n=16). The sham group (n=16) consisted of rats fed
      on basal diet. After twelve weeks blood was collected from all animals for
      estimation of lipid and angiotensin II (Ang II) levels along, subsequently all
      animals were sacrificed and morphologic analysis of the aorta was performed.
      Expression of SR-BI and phosphorylated extracellular signal regulated kinase 1/2
      (p-ERK1/2) protein were evaluated by Western blot. RESULTS: After twelve weeks of
      treatment with urolithin A, there was a significant decrease in the plasma lipid
      and Ang II levels and improvement of aortic lesion compared with the sham group.
      There was an increased expression of SR-BI and inhibition of p-ERK1/2 (p<0.05).
      The expression of SR-BI was inversely correlated with levels of Ang II.
      CONCLUSION: From the results it can be safely concluded that administration of
      urolithin A attenuates atherosclerosis via upregulation of SR-BI expression and
      inhibition of p-ERK1/2 levels.

PMID- 29660656
TI  - Comparison of liquid hot water, very dilute acid and alkali treatments for
      enhancing enzymatic digestibility of hazelnut tree pruning residues.
AB  - The effect of pretreatments on the composition of the hazelnut tree pruning
      residue (HTPR) and on the digestibility of the cellulose was investigated. The
      liquid hot water (LHW) and the very dilute acid (VDA) treatments were effective
      in solubilizing hemicellulose. The cellulose conversion increased up to around
      60% (corresponding to 32-36 g/L glucose) with decreasing hemicellulose
      concentration in the pretreated HTPR. The alkali treatment provided partial
      delignification, however, the glucose production was comparably lower. Combining
      the hemicellulose removal and the delignification effect of different
      pretreatments in two-stage processes (LHW-alkali and VDA-alkali treatments)
      enhanced the cellulose concentration in the solids, but not the amount of glucose
      released in the enzymatic digestion. These results suggested that the
      hemicellulose was the main barrier against the conversion of cellulose in the LHW
      and VDA treated HTPR and the glucose in the hydrolysis medium inhibited the
      cellulase activity, which prevented the complete conversion of cellulose.

PMID- 29660657
TI  - Hydrothermal processing as pretreatment for efficient production of ethanol and
      biogas from municipal solid waste.
AB  - Organic fraction of municipal solid waste (OFMSW) is dominated by carbohydrates,
      including starch-based and lignocellulosic materials. The OFMSW was
      hydrothermally pretreated at 100-160  degrees C for 0-60 min, and then assessed
      for enzymatic ethanol production, followed by biogas production from the
      stillage. The highest glucose yield of 520 g/Kg of dry OFMSW, corresponding to
      131% increase compared to that of the untreated OFMSW, was obtained after the
      pretreatment and enzymatic hydrolysis. Through ethanolic fermentation by an
      inhibitory tolerant fungus, Mucor indicus, 191.10 g ethanol/Kg of dry OFMSW was
      obtained, which was a 140.9% improvement in the ethanol yield compared to that
      from the untreated one. Methane production from the stillage (waste residues)
      resulted in 156 L/Kg OFMSW. In other words, a total of 10,774 KJ energy/Kg of dry
      OFMSW was generated at the best conditions.

PMID- 29660658
TI  - Nuclease expression in efficient polyhydroxyalkanoates-producing bacteria could
      yield cost reduction during downstream processing.
AB  - Industrial manufacturing of polyhydroxyalkanoates (PHAs) requires purification of
      PHAs granules from high-cell-density cultures. Cells are broken by homogenization
      and PHAs granules are cleansed and treated to obtain PHAs latexes. However, cell
      lysis releases large amounts of DNA which results in an increasing viscosity of
      the medium, hampering the following downstream steps. Drop in viscosity is
      generally achieved by costly procedures such as heat treatment or the
      supplementation of hypochlorite and commercially available nucleases. Searching
      for a cost-effective solution to this issue, a nuclease gene from Staphylococcus
      aureus has been integrated into two efficient PHAs-producing bacteria:
      Cupriavidus necator DSM 545 and Delftia acidovorans DSM 39. Staphylococcal
      nuclease has been proficiently expressed in both microbial hosts without
      affecting PHAs production. Moreover, the viscosity of the lysates of recombinant
      C. necator cells was greatly reduced, indicating that the engineered strain is
      expected to yield large reduction cost in PHAs downstream processing.

PMID- 29660659
TI  - Enrichment of bio-oil after hydrothermal liquefaction (HTL) of microalgae C.
      vulgaris grown in wastewater: Bio-char and post HTL wastewater utilization
      studies.
AB  - In this study, bio-oil was produced through hydrothermal liquefaction (HTL) of C.
      vulgaris biomass cultivated in wastewater and was enriched into transportation
      fuels. Bio-oil yield was 29.37% wt at 300  degrees C, 60 min, at 15 g/200 mL
      biomass loading rate with 3% wt nano ZnO catalyst loading. Applying catalyst
      reduced oxygen and nitrogen content in bio-oil and increased its calorific value
      (19.6 +/- 0.8 MJ/Kg). Bio-oil was enriched through liquid-liquid extraction (LLE)
      and higher yield was obtained at 30  degrees C for dichloromethane solvent (18.2%
      wt). Compounds of enriched oil were within the petro-diesel range (C8-C21). Bio
      char after HTL process was activated and used as adsorbent in wastewater
      treatment process to remove organic pollutants (COD, NO3, NH3 and PO4). Treated
      wastewater can be supplied as growth medium for microalgae cultivation in further
      experiments. Nearly 3-4 times the nanocatalyst can be reused in the HTL process.

PMID- 29660660
TI  - Bioaugmentation strategy for enhancing anaerobic digestion of high C/N ratio
      feedstock with methanogenic enrichment culture.
AB  - To investigate whether bioaugmentation could improve the digestion performance of
      high C/N ratio feedstock without co-digestion with nitrogen-rich substrate,
      different forms of enriched methanogenic culture were introduced to the
      continuous feed digesters. The performance efficiency of bioaugmentation on
      digestion improvement was compared. The effect of bioaugmentation on microbial
      community composition was revealed as well. Results demonstrated that routine
      bioaugmentation with liquid culture (containing the microbes and the medium
      remains) showed the best performance, with the organic loading rate (OLR),
      methane percentage, volumetric methane production (VMP) and volatile solid
      methane production (VSMP) higher at 1.0 g L-1 d-1, 24%, 0.22 L L-1 d-1 and 0.23 L
      g-1 VS d-1 respectively, compared to the non-bioaugmentation control. Whole
      genome pyrosequencing analysis suggested that consecutive microbial consortium
      addition could reconstruct the methanogens community by increasing the
      populations of acetoclastic methanogens Methanothrix, which could accelerate the
      degradation of acetate and methane production.

PMID- 29660661
TI  - Enhanced bioreduction synthesis of ethyl (R)-4-chloro-3-hydroybutanoate by
      alkalic salt pretreatment.
AB  - In this study, biomass-hydrolysate was used for enhancing the bioreduction of
      ethyl 4-chloro-3-oxobutanoate (COBE). Firstly, dilute alkalic salt pretreatment
      was attempted to pretreat bamboo shoot shell (BSS). It was found that enzymatic
      in situ hydrolysis of 20-50 g/L BSS pretreated with dilute alkalic salts (0.4%
      Na2CO3, 0.032% Na2S) at 7.5% sulfidity by autoclaving at 110  degrees C for 40
      min gave sugar yields at 59.9%-73.5%. Moreover, linear relationships were
      corrected on solid recovery-total delignification-sugar yield. In BSS
      hydrolysates, xylose and glucose could promote the reductase activity of
      recombinant E. coli CCZU-A13. Compared with glucose, hydrolysate could increase
      the reductase activity by 1.35-folds. Furthermore, the cyclohexane-hydrolysate
      (10:90, v/v) biphasic media containing ethylene diamine tetraacetic acid (EDTA,
      40 mM) and l-glutamine (150 mM) was built for the effective biosynthesis of ethyl
      (R)-4-chloro-3-hydroxybutanoate [(R)-CHBE] (94.6% yield) from 500 mM COBE. In
      conclusion, this strategy has high potential for the effective biosynthesis of
      (R)-CHBE (>99% e.e.).

PMID- 29660662
TI  - Green alga cultivation with monoethanolamine: Evaluation of CO2 fixation and
      macromolecule production.
AB  - This study aimed to assess the growth of Chlorella strains isolated from adverse
      environments at various concentrations of monoethanolamine (MEA), evaluating the
      CO2 fixation and macromolecule production. For this purpose, the green algae
      Chlorella sp. and Chlorella fusca LEB 111 were tested against five concentrations
      of MEA: 50, 75, 100, 200 and 300 mg L-1. The strain C. fusca LEB 111 exhibited
      higher tolerance to MEA as well as higher accumulation of dissolved inorganic
      carbon and efficiency of CO2 utilization (approximately 37.0% w w-1) with the
      addition of 100 and 150 mg L-1 of MEA. In addition, the highest carbohydrate
      productivity and the highest lipid productivity were obtained with 50 and 100 mg
      L-1 of MEA, respectively. Thus, the absorbent increased the carbon concentration
      in the medium, and its use in culture can be exploited by C. fusca LEB 111 to
      produce higher macromolecule concentrations.

PMID- 29660663
TI  - Developing an UPLC-MS/MS method to quantify maoecrystal A in rat plasma:
      Application to a pharmacokinetic study.
AB  - Maoecrystal A (MC-A) is an ent-kaurane-type diterpene isolated from Rabdosia
      eriocalyx (Dunn) Hara. MC-A has been reported to show different types of
      pharmacological activities, including anticancer, anti-inflammatory and
      bacteriostatic functions. However, bioanalysis of MC-A has not been reported. The
      purpose of this study is to develop an UPLC-MS/MS method to quantify MC-A in
      plasma and determine its pharmacokinetic properties using an animal model. The
      separation was performed using a Waters HSS T3 column (50 mm * 2.1 mm, 1.8 MUm,
      Waters Corp., Milford, MA, USA) with methanol and water containing 0.1% of formic
      acid as the mobile phases. The mass analysis was performed in a Waters Xevo TQ
      mass spectrometer using multiple reaction monitoring (MRM) in positive scan mode.
      Protein precipitation was used to extract the drug from rat plasma samples. The
      calibration curve is linear in the concentration range 0.49-2000.0 ng/mL. The
      extraction recovery and the matrix effect were 78.11 to 91.72% and 90.38 to
      98.02%, respectively. The RSD of inter/intra-day precisions were <13.72% and the
      accuracy was >86.41%. Stability studies showed that MC-A was stable (RSD <
      14.98%) at different conditions (i.e., short-term, long-term, bench, and three
      freeze-thaw cycles) in rat plasma. The method was successfully applied to a
      pharmacokinetic study using rats through oral and intravenous administration
      routes. The oral bioavailability of MC-A was only 2.9%. Further studies are
      needed to determine the absorption and metabolism in order to improve the oral
      bioavailability of MC-A.

PMID- 29660664
TI  - Nano-flow vs standard-flow: Which is the more suitable LC/MS method for
      quantifying hepcidin-25 in human serum in routine clinical settings?
AB  - Hepcidin-25 peptide is a biomarker which is known to have considerable clinical
      potential for diagnosing iron-related diseases. Developing analytical methods for
      the absolute quantification of hepcidin is still a real challenge, however, due
      to the sensitivity, specificity and reproducibility issues involved. In this
      study, we compare and discuss two MS-based assays for quantifying hepcidin, which
      differ only in terms of the type of liquid chromatography (nano LC/MS versus
      standard LC/MS) involved. The same sample preparation, the same internal
      standards and the same MS analyzer were used with both approaches. In the field
      of proteomics, nano LC chromatography is generally known to be more sensitive and
      less robust than standard LC methods. In this study, we established that the
      performances of the standard LC method are equivalent to those of our previously
      developed nano LC method. Although the analytical performances were very similar
      in both cases. The standard-flow platform therefore provides the more suitable
      alternative for accurately determining hepcidin in clinical settings.

PMID- 29660665
TI  - Investigation of anti-Hepatitis C virus, sofosbuvir and daclatasvir, in pure
      form, human plasma and human urine using micellar monolithic HPLC-UV method and
      application to pharmacokinetic study.
AB  - Simultaneous determination of sofosbuvir (SOF), and daclatasvir (DAC) in their
      dosage forms, human urine and human plasma using simple and rapid micellar high
      performance liquid chromatographic method coupled with UV detection (HPLC-UV) had
      been developed and validated. These drugs are described as co-administered for
      treatment of Hepatitis C virus (HCV). HCV is the cause of Hepatitis C and some
      cancers such as liver cancer (hepatocellular carcinoma) and lymphomas in humans.
      Separation and quantitation were carried out on anonyxTM C8 monolithic (100 * 4.6
      mm (i.d.) analytical column maintained at 25  degrees C. The mobile phase
      consisted of 0.1 M sodium dodecyl sulfate (SDS) solution containing 20% (V/V) n
      propanolol and 0.3% (V/V) triethylamine and pH was adjusted to 6.5 using 0.02 M
      phosphoric acid, respectively. The retention times of SOF and DAC were 4.8 min,
      and 6.5 min, respectively. Measurements were made at flow rate of 0.5 mL/min with
      injection volume of 20 MUL and ultraviolet (UV) detection at 226 nm. Linearity of
      SOF and DAC was obtained over concentration ranges of 50-400, and 40-400 ng/mL,
      respectively in pure form, 60-300 and 50-300 ng/mL, respectively for human plasma
      and over 50-400, and 40-400 ng/mL, respectively for human urine with correlation
      coefficient >0.999. The proposed method demonstrated excellent intra- and inter
      day precision and accuracy. The suggested method was applied for determination of
      the drugs in pure, dosage form, and in real human plasma, real human urine and
      drug-dissolution test of their tablets. The obtained results have been
      statistically compared to reported method to give a conclusion that there is no
      significant differences.

PMID- 29660666
TI  - On-line supercritical fluid extraction-supercritical fluid chromatography-mass
      spectrometry of polycyclic aromatic hydrocarbons in soil.
AB  - On-line supercritical fluid extraction - supercritical fluid chromatography -
      mass spectrometry (SFE-SFC-MS) has been applied for the determination of
      polycyclic aromatic hydrocarbons (PAHs) in soil. The purpose of this study was to
      develop and validate the first on-line SFE-SFC-MS method for the quantification
      of PAHs in various types of soil. By coupling the sample extraction on-line with
      chromatography and detection, sample preparation is minimized, diminishing sample
      loss and contamination, and significantly decreasing the required extraction
      time. Parameters for on-line extraction coupled to chromatographic analysis were
      optimized. The method was validated for concentrations of 10-1500 ng of PAHs per
      gram of soil in Certified Reference Material (CRM) sediment, clay, and sand with
      R2 >= 0.99. Limits of detection (LOD) were found in the range of 0.001-5 ng/g,
      and limits of quantification (LOQ) in the range of 5-15 ng/g. The method
      developed in this study can be effectively applied to the study of PAHs in the
      environment, and may lay the foundation for further applications of on-line SFE
      SFC-MS.

PMID- 29660667
TI  - High-performance thin-layer chromatographic methods for the determination of
      febuxostat and febuxostat/diclofenac combination in human plasma.
AB  - Two simple, sensitive and specific high-performance thin-layer chromatographic
      (HPTLC) methods were developed for the determination of febuxostat (FEB)
      individually, and simultaneously with diclofenac (DIC) in human plasma. Method A
      presents the first HPTLC-ultraviolet attempt for FEB determination in human
      plasma. FEB was separated from endogenous plasma components (at hRF = 70) with
      ethyl acetate-methanol-water (9:2:1, v/v) mixture as mobile phase and quantified
      by densitometry at its lambdamax (315 nm). Method B is considered the first
      attempt for the simultaneous determination of FEB and DIC in human plasma. A
      mixture of petroleum ether-chloroform-ethyl acetate-formic acid (7.5:1:2.5:0.25,
      v/v) was used as the mobile phase. The two drugs were separated at hRF of 39 and
      60 for FEB and DIC, respectively. FEB and DIC were quantified by densitometry at
      their isoabsorptive point (289 nm). FEB calibration plots were linear between 0.1
      and 7 MUg mL-1 in both methods A and B. In method B, DIC showed linear response
      in the range of 0.08-8 MUg mL-1. Sample preparation was performed by liquid
      liquid extraction using diethyl ether. Both methods did not record any
      interference from plasma matrix, the studied drugs' metabolites or their
      decomposition products. They were successfully applied for the determination of
      the studied drugs in healthy male volunteers after oral administration of FEB or
      FEB/DIC dosage forms. FEB plasma concentration increased significantly when given
      with DIC. The proposed methods provided very simple, rapid and cheap approaches
      that might be attractive for the future pharmacokinetic and bioavailability
      studies of FEB and/or DIC.

PMID- 29660668
TI  - Supercritical fluid chromatography applied to the highly selective isolation of
      urinary steroid hormones prior to GC/MS analysis.
AB  - To assess the presence of prohibited anabolic substances used to promote growth
      in livestock, calf urine is the most relevant matrix. However, the sample
      preparation methods (required to remove unwanted matrix components and
      fractionate isobaric species that may be unresolved by gas chromatography- mass
      spectrometry GC/MS) are long and complex. In this context, semi-preparative
      supercritical fluid chromatography (SFC) was considered to possibly simplify the
      sample preparation in reducing the number of procedures. Fifteen stationary
      phases were screened with SFC combined with UV and evaporative light-scattering
      detection (ELSD), among which two columns (Cosmosil pi-NAP and Princeton DIOL)
      were retained for their ability to isolate steroid hormones from other matrix
      components and, for the second column, for the additional possibility to
      fractionate steroid hormones into different families (estrogens, mono
      hydroxylated and di-hydroxylated androgens). The fractions were further analysed
      with GC/MS showing the benefit of class fractionation. The final method allows
      for significant time, solvent and money savings compared to the previously widely
      used method (solid-phase extraction combined with semi-preparative high
      performance liquid chromatography).

PMID- 29660669
TI  - The systemic inflammatory response syndrome criteria and their differential
      association with mortality.
AB  - PURPOSE: Despite the recent Sepsis-3 consensus, the Systemic Inflammatory
      Response Syndrome (SIRS) criteria continue to be assessed and recommended. Such
      use implies equivalence and interchangeability of criteria. Thus, we aimed to
      test whether such criteria are indeed equivalent and interchangeable. MATERIALS
      AND METHODS: From 2000 to 2015, we identified patients with infection, organ
      failure, and at least one SIRS criterion in 179 Intensive Care Units in Australia
      and New. Zealand. We studied the association of different SIRS criteria with
      hospital mortality. RESULTS: Among 131,016 patients with infection and organ
      failure, mortality increased from 10.6% for the respiratory rate criterion to
      15.8% for the heart rate criterion (P<0.01); from 10.1% for the high leukocyte
      count criterion to 20.0% for a low count and from 10.1% for a high temperature to
      14.4% for a low temperature criterion. With any two SIRS criteria, hospital
      mortality varied from 11.5% to 30.8% depending on the combination of criteria.
      This difference remained unchanged after adjustments and was consistent over
      time. CONCLUSIONS: Different individual and combinations of SIRS criteria were
      associated with marked differences in hospital mortality. These differences
      remained unchanged after adjustment and over time and imply that individual SIRS
      criteria are not equivalent or interchangeable.

PMID- 29660670
TI  - Efficacy of early passive tilting in minimizing ICU-acquired weakness: A
      randomized controlled trial.

PMID- 29660671
TI  - Computational study of molecular electrostatic potential, docking and dynamics
      simulations of gallic acid derivatives as ABL inhibitors.
AB  - Chronic myeloid leukemia (CML), a hematological malignancy arises due to the
      spontaneous fusion of the BCR and ABL gene, resulting in a constitutively active
      tyrosine kinase (BCR-ABL). Pharmacological activity of Gallic acid and 1,3,4
      Oxadiazole as potential inhibitors of ABL kinase has already been reported.
      Objective of this study is to evaluate the ABL kinase inhibitory activity of
      derivatives of Gallic acid fused with 1,3,4-Oxadiazole moieties. Attempts have
      been made to identify the key structural features responsible for drug likeness
      of the Gallic acid and the 1,3,4-Oxadiazole ring using molecular electrostatic
      potential maps (MESP). To investigate the inhibitory activity of Gallic acid
      derivatives towards the ABL receptor, we have applied molecular docking and
      molecular dynamics (MD) simulation approaches. A comparative study was performed
      using Bosutinib as the standard which is an approved CML drug acting on the same
      receptor. Furthermore, the novel compounds designed and reported here in were
      evaluated for ADME properties and the results indicate that they show acceptable
      pharmacokinetic properties. Accordingly these compounds are predicted to be drug
      like with low toxicity potential.

PMID- 29660672
TI  - Biotechnological and protein-engineering implications of ancestral protein
      resurrection.
AB  - Approximations to the sequences of ancestral proteins can be derived from the
      sequences of their modern descendants. Proteins encoded by such reconstructed
      sequences can be prepared in the laboratory and subjected to experimental
      scrutiny. These 'resurrected' ancestral proteins often display remarkable
      properties, reflecting ancestral adaptations to intra-cellular and extra-cellular
      environments that differed from the environments hosting modern/extant proteins.
      Recent experimental and computational work has specifically discussed high
      stability, substrate and catalytic promiscuity, conformational
      flexibility/diversity and altered patterns of interaction with other sub-cellular
      components. In this review, we discuss these remarkable properties as well as
      recent attempts to explore their biotechnological and protein-engineering
      potential.

PMID- 29660673
TI  - Inspective and toxicological survey of the poisoned baits and bites.
AB  - Cases of intentional animal poisonings are still widespread in Italy, even if the
      improper or malicious use of poisoned baits is banned. This represents a serious
      threat to pets as well as wildlife species, but also an environmental and human
      health concern. A retrospective study was performed based on baits sent for
      toxicological analysis to the laboratories of Istituto Zooprofilattico
      Sperimentale del Mezzogiorno (IZSM) in Southern Italy over a five year period.
      Analyses were carried out by using different analytical techniques in relation to
      the toxicants. Results show a trend different from other countries, as well as
      from that reported for Northern Italy. The molluscicide metaldehyde proved to be
      the most common substance detected in our laboratory (63.9%) followed by
      organochlorine insecticides (29.2%), organophosphine insecticides (11.1%) and
      anticoagulant rodenticides (9.7%). Other rodenticides, such as strychnine and
      zinc phosphide were detected only one time in baits. Among the organochlorine
      insecticide, endosulfan (both alpha and beta isomers) occurred as the main
      poisoning agent. The incidence of poisoning cases detected in the present survey
      is extremely alarming and pointed out that actions have to be made to reduce this
      illegal practice and its environmental impact.

PMID- 29660674
TI  - The relation of borderline personality disorder to aggression, victimization, and
      institutional misconduct among prisoners.
AB  - OBJECTIVE: Borderline personality disorder (BPD) is highly prevalent among
      incarcerated populations; however, research has yet to examine whether prisoners
      diagnosed with BPD experience greater interpersonal dysfunction and institutional
      misconduct while incarcerated. PROCEDURE: This study drew from a sample of 184
      male and female prisoners diagnosed with major depressive disorder (MDD) in a
      randomized trial of depression treatment. The presence of a BPD diagnosis (n =
      69) was analyzed as a predictor of disciplinary incidents/infractions (i.e.,
      fights, arguments with staff, disciplinary infractions, isolation), time spent in
      isolation, and types of aggression and victimization experiences during
      incarceration. RESULTS: There was a trend suggesting prisoners with BPD were
      about twice as likely as those without BPD to report disciplinary
      incidents/infractions (OR = 1.76 [0.93, 3.32], p = 0.075). Having a BPD diagnosis
      was unrelated to time in isolation and overall aggression and victimization.
      However, prisoners with BPD were more likely than those without BPD to perpetrate
      and be victimized by psychological aggression. Due to high rates of antisocial
      personality disorder (ASPD) in the sample as a whole (72%), additional analyses
      compared outcomes across prisoners with no BPD or ASPD diagnosis, BPD diagnosis
      only, ASPD diagnosis only, and comorbid BPD and ASPD. Prisoners with comorbid BPD
      and ASPD were no more likely than prisoners with ASPD only to report disciplinary
      incidents/infractions, but were significantly more likely than those with ASPD
      only to report perpetrating and being victimized by psychological aggression.
      CONCLUSIONS: Among prisoners with MDD, those with a BPD diagnosis have increased
      risk of psychological aggression and disciplinary infractions during
      incarceration.

PMID- 29660675
TI  - Improvements in event-related desynchronization and classification performance of
      motor imagery using instructive dynamic guidance and complex tasks.
AB  - BACKGROUND AND OBJECTIVE: The motor-imagery based brain-computer interface
      supplies a potential approach for motor-impaired patients, not only to control
      rehabilitation facilities but also to promote recovery from motor dysfunctions.
      To improve event-related desynchronization during motor imagery and obtain
      improved brain-computer interface classification accuracy, we introduce dynamic
      video guidance and complex motor tasks to the motor imagery paradigm. METHODS:
      Eleven participants were included in the experiment; 64-channel
      electroencephalographic data were collected and analyzed during four motor
      imagery tasks with different guidance. Time-frequency analysis, spectral-time
      variation analysis, topographical distribution maps, and statistical analysis
      were utilized to analyze the event-related desynchronization patterns. Common
      spatial patterns were used to extract spatial pattern features and support vector
      machines were used to discriminate the offline classification accuracies in three
      bands (the alpha band, beta band, alpha and beta band) for comparison. RESULTS:
      The experimental outcomes showed that complex motor imagery tasks coupled with
      dynamic video guidance induced significantly stronger event-related
      desynchronization than other paradigms, which use simple motor imagery tasks or
      static guidance. Similar results were obtained during analysis of the motor
      imagery brain-computer interface classification performance; namely, the highest
      average classification accuracy in complex and dynamic guidance was improved by
      approximately 14%, compared with static guidance. For individually specified
      paradigms, all participants obtained a classification accuracy that exceeded or
      was equal to 87.5%. CONCLUSIONS: This study provides an optional route to enhance
      the event-related desynchronization activities and classification accuracy of a
      motor imagery brain-computer interface through optimization of motor imagery
      tasks and instructive guidance.

PMID- 29660676
TI  - Cerebrovascular myocardium-tissue embolism: a rare complication of heart surgery:
      autopsy case report.

PMID- 29660677
TI  - Multi-technique characterisation of commercial alizarin-based lakes.
AB  - The characterization of ancient and modern alizarin-based lakes is a largely
      studied topic in the literature. Analytical data on contemporary alizarin-based
      lakes, however, are still poor, though of primary importance, since these lakes
      might be indeed present in contemporary and fake paintings as well as in
      retouchings. In this work we systematically investigate the chemical composition
      and the optical features of fifteen alizarin-based lakes, by a multi-analytical
      technique approach combining spectroscopic methods (i.e. Energy Dispersive X-ray
      Fluorescence Spectroscopy, EDXRF; Attenuated Total Reflectance Fourier-Transform
      Infrared Spectroscopy, ATR-FTIR; X-ray Powder Diffraction, XRD; UV induced
      fluorescence and reflectance spectroscopies) and chromatography (i.e. High
      performance Liquid Chromatography coupled with a Photodiode Array Detector, HPLC
      PDA). Most of the samples contain typical compounds from the natural roots of
      madder, as occurring in ancient and modern lakes, but in two samples (23600
      Kremer-Pigmente and alizarin crimson-Zecchi) any anthraquinonic structures were
      identified, thus leading to hypothesize the presence of synthetic dyes. The
      detection of lucidin primeveroside and ruberythrique acid in some lakes suggest
      the use of Rubia tinctorum. One sample (23610-Kremer-Pigmente) presents alizarin
      as the sole compound, thereby revealing to be a synthetic dye. Moreover,
      gibbsite, alunite and kaolinite were found to be used as substrates and/or
      mordants. Visible absorption spectra of the anthraquinonic lakes show two main
      absorption bands at about 494-511nm and 537-564nm, along with a shoulder at about
      473-479nm in presence of high amounts of purpurin. Finally, from the results
      obtained by UV induced fluorescence spectroscopy it is possible to figure out
      that, although it is commonly assumed that the madder lake presents an orange
      pink fluorescence, the inorganic compounds, added to the recipe, could induce a
      quenching phenomenon or an inhibition of the fluorescence, as occurring in some
      commercial alizarin-based lakes.

PMID- 29660678
TI  - Fast detection of fenthion on fruit and vegetable peel using dynamic surface
      enhanced Raman spectroscopy and random forests with variable selection.
AB  - Dynamic surface-enhanced Raman spectroscopy (D-SERS) based on the state change of
      the substrate not only significantly enhances but also provides a highly
      reproducible Raman signal. Hence, we develop a fast and accurate method for the
      detection of fenthion on fruit and vegetable peel using D-SERS and random forests
      (RF) with variable selection. With uniform Ag nanoparticles, the dynamic spectra
      of fenthion solution at different concentrations were obtained using D-SERS, and
      fenthion solution greater than or equal to 0.05mg/L can be detected. Then, the
      quantitative analysis models of fenthion were developed by RF with variable
      selection for spectra of different range. The model of best performance is
      developed by RF and spectra of characteristic range with higher RF importance
      (top 40%), and the root mean square error of cross-validation is 0.0101mg/L.
      Moreover, the fenthion residue of tomato, pear, and cabbage peel were extracted
      by a swab dipped in ethanol and analyzed using the above method to further
      validate the practical effect. Compared to gas chromatography, the maximal
      relative deviation is below 12.5%, and the predicted recovery is between 87.5%
      and 112.5%. Accordingly, D-SERS and RF with variable selection can realize the
      fast, simple, ultrasensitive, and accurate analysis of fenthion residue on fruit
      and vegetable peel.

PMID- 29660679
TI  - Rapid quantitation of atorvastatin in process pharmaceutical powder sample using
      Raman spectroscopy and evaluation of parameters related to accuracy of analysis.
AB  - The purpose of this study was to determine the atorvastatin (ATV) content in
      process pharmaceutical powder sample using Raman spectroscopy. To establish the
      analysis method, the influence of the type of Raman measurements (back-scattering
      or transmission mode), preparation of calibration sample (simple admixing or
      granulation), sample pre-treatment (pelletization), and spectral pretreatment on
      the Raman spectra was investigated. The characteristic peak of the active
      compound was more distinctively detected in transmission Raman mode with a laser
      spot size of 4mm than in the back-scattering method. Preparation of calibration
      samples by wet granulation, identical to the actual manufacturing process,
      provided unchanged spectral patterns for the in process sample, with no changes
      and/or shifts in the spectrum. Pelletization before Raman analysis remarkably
      improved spectral reproducibility by decreasing the difference in density between
      the samples. Probabilistic quotient normalization led to accurate and consistent
      quantification of the ATV content in the calibration samples (standard error of
      cross validation: 1.21%). Moreover, the drug content in the granules obtained
      from five commercial batches were reliably quantified, with no statistical
      difference (p=0.09) with that obtained by HPLC assay. From these findings, we
      suggest that transmission Raman analysis may be a fast and non-invasive method
      for the quantification of ATV in actual manufacturing processes.

PMID- 29660680
TI  - Phase composition and morphological characterization of human kidney stones using
      IR spectroscopy, scanning electron microscopy and X-ray Rietveld analysis.
AB  - Pathological calcification in human urinary tract (kidney stones) is a common
      problem affecting an increasing number of people around the world. Analysis of
      such minerals or compounds is of fundamental importance for understanding their
      etiology and for the development of prophylactic measures. In the present study,
      structural characterization, phase quantification and morphological behaviour of
      thirty three (33) human kidney stones from eastern India have been carried out
      using IR spectroscopy (FT-IR), powder X-ray diffraction (PXRD) and scanning
      electron microscopy (SEM). Quantitative phase composition of kidney stones has
      been analyzed following the Rietveld method. Based on the quantitative estimates
      of constituent phases, the calculi samples have been classified into oxalate
      (OX), uric acid (UA), phosphate (PH) and mixed (MX) groups. Rietveld analysis of
      PXRD patterns showed that twelve (36%) of the renal calculi were composed
      exclusively of whewellite (calcium oxalate monohydrate, COM). The remaining
      twenty one (64%) stones were mixture of phases with oxalate as the major
      constituent in fourteen (67%) of these stones. The average crystallite size of
      whewellite in oxalate stones, as determined from the PXRD analysis, varies
      between 93 (1) nm and 202 (3) nm, whereas the corresponding sizes for the uric
      acid and struvite crystallites in UA and PH stones are 79 (1)-155 (4) nm and 69
      (1)-123(1) nm, respectively. The size of hydroxyapatite crystallites, 10 (1)-21
      (1) nm, is smaller by about one order of magnitude compared to other minerals in
      the kidney stones. A statistical analysis using fifty (50) kidney stones (33
      calculi from the present study and 17 calculi reported earlier from our
      laboratory) revealed that the oxalate group (whewellite, weddellite or mixture of
      whewellite and weddellite as the major constituent) is the most prevalent (82%)
      kidney stone type in eastern India.

PMID- 29660681
TI  - Etching-dependent fluorescence quenching of Ag-dielectric-Au three-layered
      nanoshells: The effect of inner Ag nanosphere.
AB  - In this report, Ag-dielectric-Au three-layered nanoshells with controlled inner
      core size were synthesized. The fluorescence emission of the rhodamine 6G (R6G)
      could be quenched by the three-layered nanoshells distinctly. What's more, the
      fluorescence quenching efficiency could be further improved by tuning the etching
      of inner Ag nanosphere. The maximum fluorescence quenching efficiency is obtained
      when the separate layer just appears between the inner Ag core and the outer Au
      shell. Whereas the fluorescence quenching efficiency is weakened when no gaps
      take place around the inner Ag core or the separate layer is too thick and
      greater than 13nm. The fluorescence quenching properties of the Ag-dielectric-Au
      three-layered nanoshells with different initial sizes of the Ag nanoparticles are
      also studied. The maximum fluorescence quenching efficiency is obtained when the
      three-layered nanoshells are synthesized based on the Ag nanoparticles with 60nm,
      which is better than others two sizes (42 and 79nm). Thus we believe that the
      size of initial Ag nanospheres also greatly affects the optimized fluorescence
      quenching efficiency. These results about fluorescence quenching properties of Ag
      dielectric-Au three-layered nanoshells present a potential for design and
      fabrication of fluorescence nanosensors based on tuning the geometry of the inner
      core and the separate layer.

PMID- 29660682
TI  - Insights into the binding behavior of bovine serum albumin to black carbon
      nanoparticles and induced cytotoxicity.
AB  - Black carbon (BC) is a main component of particulate matter (PM2.5). Due to their
      small size (<100nm), inhaled ultrafine BC nanoparticles may penetrate the lung
      alveoli, where they interact with surfactant proteins and lipids, causing more
      serious damage to human health. Here, BC was analyzed to investigate the binding
      mechanism of its interaction with protein and induction of cytotoxicity changes.
      The binding process and protein conformation between BC and a serum protein
      (bovine serum albumin, BSA) were monitored by using a fluorescence quenching
      technique and UV-vis absorption, Fourier transform infrared (FTIR) and circular
      dichroism (CD) spectroscopies. The experimental results revealed that the
      fluorescence quenching of BSA induced by BC was a static quenching process and
      the hydrophobic force played the critical role in the interaction. The native
      conformation of BSA on the BC surface was slightly disturbed but obvious
      structural unfolding of the secondary structure did not occur. In the
      cytotoxicity study, BC nanoparticles with low concentrations exhibited strong
      toxicity towards BEAS-2B cells. However, the toxicity of BC nanoparticles could
      be mitigated by the presence of BSA. Therefore, proteins in biological fluids
      likely reduce the toxic effect of BC on human health. These findings delineated
      the binding mechanism and the toxicity between BC and the BSA-BC system,
      contributing to the understanding of the biological effects of BC exposure on
      human health in polluted atmospheres.

PMID- 29660683
TI  - Crystal growth, polarized spectroscopy and Judd-Ofelt analysis of Tb:YAlO3.
AB  - Tb3+-doped YAlO3 (YAP) single crystal was grown by Czochralski (Cz) method. Based
      on the polarized absorption spectra, the spectroscopic parameters were calculated
      to be Omega2=3.49*10-20cm2, Omega4=5.87*10-20cm2 and Omega6=2.55*10-20cm2, and
      then the spontaneous transition rate, fluorescent branching ratio and radiative
      lifetime of 5D4 multiplet were obtained. The yellow emission cross sections of
      5D4->7F4 transition were calculated to be 1.72*10-22cm2, 2.73*10-22cm2 and
      2.65*10-22cm2 for a, b and c polarization, respectively. The fluorescence
      lifetime of the 5D4 multiplet was fitted to be 1.72ms. All the data indicate that
      Tb:YAP crystal is a promising candidate for yellow laser operation.

PMID- 29660684
TI  - Determination of diclofenac sodium by resonance light scattering method using
      silver nanoparticles as probe.
AB  - A sensitive, simple and novel method was developed to determine diclofenac sodium
      (DS) using silver nanoparticles (AgNPs) as probe by resonance light scattering
      (RLS) technique. It was found that DS could quench the RLS intensity of AgNPs.
      Moreover, the decrease in RLS intensity was linearly correlated to the
      concentration of DS over the range of 0.01-2.0MUgmL-1. DS can be measured in a
      short time (5min) without any complicated or time-consuming sample pretreatment
      process. Parameters that affect the RLS intensities such as pH, concentration of
      AgNPs, reaction time, electrolyte concentration, and coexisting substances were
      systematically investigated and optimized. The results showed that the method had
      a very good selectivity and could be used conveniently for the determination of
      DS. The limit of detection (LOD) was 2.85ngmL-1 (3sigma), and the relative
      standard deviation (RSD) was less than 3.6% (n=6). Possible mechanism for the RLS
      changes of AgNPs in the presence of DS was discussed and the method was
      successfully applied for the analysis of tablets and urine samples.

PMID- 29660685
TI  - Evidence of Wnt/beta-catenin alterations in brain and bone of a tauopathy mouse
      model of Alzheimer's disease.
AB  - Low bone mineral density (BMD) is a significant comorbidity in Alzheimer's
      disease (AD) and may reflect systemic regulatory pathway dysfunction. Low BMD has
      been identified in several AD mouse models selective for amyloid-beta or tau
      pathology, but these deficits were attributed to diverse mechanisms. In this
      study, we identified common pathophysiological mechanisms accounting for bone
      loss and neurodegeneration in the htau mouse, a tauopathy model with an early low
      BMD phenotype. We investigated the Wnt/beta-catenin pathway-a cellular signaling
      cascade linked to both bone loss and neuropathology. We showed that low BMD
      persisted in male htau mice aged from 6 to 14 months, remaining significantly
      lower than tau-null and C57BL/6J controls. Osteogenic gene expression in female
      and male htau mice was markedly reduced from controls, indicating impaired bone
      remodeling. In both the bone and brain, htau mice showed alterations in Wnt/beta
      catenin signaling genes suggestive of increased inhibition of this pathway. These
      findings implicate dysfunctional Wnt signaling as a potential target for
      addressing bone loss in AD.

PMID- 29660686
TI  - Measurements of the energy distribution of a high brightness rubidium ion beam.
AB  - The energy distribution of a high brightness rubidium ion beam, which is intended
      to be used as the source for a focused ion beam instrument, is measured with a
      retarding field analyzer. The ions are created from a laser-cooled and compressed
      atomic beam by two-step photoionization in which the ionization laser power is
      enhanced in a build-up cavity. Particle tracing simulations are performed to
      ensure the analyzer is able to resolve the distribution. The lowest achieved full
      width 50% energy spread is (0.205 +/- 0.006) eV, which is measured at a beam
      current of 9 pA. The energy spread originates from the variation in the
      ionization position of the ions which are created inside an extraction electric
      field. This extraction field is essential to limit disorder-induced heating which
      can decrease the ion beam brightness. The ionization position distribution is
      limited by a tightly focused excitation laser beam. Energy distributions are
      measured for various ionization and excitation laser intensities and compared
      with calculations based on numerical solutions of the optical Bloch equations
      including ionization. A good agreement is found between measurements and
      calculations.

PMID- 29660687
TI  - Novel in-situ lamella fabrication technique for in-situ TEM.
AB  - In-situ transmission electron microscopy is rapidly emerging as the premier
      technique for characterising materials in a dynamic state on the atomic scale.
      The most important aspect of in-situ studies is specimen preparation. Specimens
      must be electron transparent and representative of the material in its
      operational state, amongst others. Here, a novel fabrication technique for the
      facile preparation of lamellae for in-situ transmission electron microscopy
      experimentation using focused ion beam milling is developed. This method involves
      the use of rotating microgrippers during the lift-out procedure, as opposed to
      the traditional micromanipulator needle and platinum weld. Using rotating
      grippers, and a unique adhesive substance, lamellae are mounted onto a MEMS
      device for in-situ TEM annealing experiments. We demonstrate how this technique
      can be used to avoid platinum deposition as well as minimising damage to the MEMS
      device during the thinning process. Our technique is both a cost effective and
      readily implementable alternative to the current generation of preparation
      methods for in-situ liquid, electrical, mechanical and thermal experimentation
      within the TEM as well as traditional cross-sectional lamella preparation.

PMID- 29660688
TI  - Implementation and validation of an improved allele specific stutter filtering
      method for electropherogram interpretation.
AB  - Modern probabilistic genotyping (PG) software is capable of modeling stutter as
      part of the profile weighting statistic. This allows for peaks in stutter
      positions to be considered as allelic or stutter or both. However, prior to
      running any sample through a PG calculator, the examiner must first interpret the
      sample, considering such things as artifacts and number of contributors (NOC or
      N). Stutter can play a major role both during the assignment of the number of
      contributors, and the assessment of inclusion and exclusion. If stutter peaks are
      not filtered when they should be, it can lead to the assignment of an additional
      contributor, causing N contributors to be assigned as N + 1. If peaks in the
      stutter position of a major contributor are filtered using a threshold that is
      too high, true alleles of minor contributors can be lost. Until now, the software
      used to view the electropherogram stutter filters are based on a locus specific
      model. Combined stutter peaks occur when a peak could be the result of both back
      stutter (stutter one repeat shorter than the allele) and forward stutter (stutter
      one repeat unit larger than the allele). This can challenge existing filters. We
      present here a novel stutter filter model in the ArmedXpertTM software package
      that uses a linear model based on allele for back stutter and applies an additive
      filter for combined stutter. We term this the allele specific stutter model (AM).
      We compared AM with a traditional model based on locus specific stutter filters
      (termed LM). This improved stutter model has the benefit of: Instances of over
      filtering were reduced 78% from 101 for a traditional model (LM) to 22 for the
      allele specific model (AM) when scored against each other. Instances of under
      filtering were reduced 80% from 85 (LM) to 17 (AM) when scored against ground
      truth mixtures.

PMID- 29660689
TI  - Quinonoid compounds via reactions of lawsone and 2-aminonaphthoquinone with alpha
      bromonitroalkenes and nitroallylic acetates: Structural diversity by C-ring
      modification and cytotoxic evaluation against cancer cells.
AB  - Morita-Baylis-Hillman acetates and alpha-bromonitroalkenes have been employed in
      cascade reactions with lawsone and 2-aminonaphthoquinone for the one-pot
      synthesis of heterocycle fused quinonoid compounds. The reactions reported here
      utilized the 1,3-binucleophilic potential of hydroxy- and aminonaphthoquinones
      and the 1,2/1,3-bielectrophilic potential of bromonitroalkenes and Morita-Baylis
      Hillman acetates for the synthesis of pyrrole and furan fused naphthoquinones.
      The synthesized compounds were evaluated against HCT-116 (human colon carcinoma
      cells), PC3 (human prostate cancer cells), HL-60 (human promyelocytic leukemia
      cells), SF295 (human glioblastoma cells) and NCI-H460 (human lung cancer cells)
      and exhibited antitumor activity with IC50 values as low as < 2 MUM. Selected
      compounds were also evaluated against OVCAR-8 (ovary), MX-1 (breast) and JURKAT
      (leukemia) cell lines. The cytotoxic potential of the quinones evaluated was also
      assayed using non-tumor cells, exemplified by peripheral blood mononuclear (PBMC)
      and L929 cells.

PMID- 29660690
TI  - New 1,2,4-triazole-Chalcone hybrids induce Caspase-3 dependent apoptosis in A549
      human lung adenocarcinoma cells.
AB  - A series of novel 1, 2, 4-triazole/chalcone hybrids was prepared and identified
      with different spectroscopic techniques. The prepared compounds showed remarkable
      cytotoxic activity against different cancer cell lines. Compounds 24, 25, 27, 41
      and 47 had shown the highest cytotoxicity among the tested compounds against
      human lung adenocarcinoma A549 cells with IC50 ranging from 4.4 to 16.04 MUM
      compared to cisplatin with IC50 of 15.3 MUM. Flow cytometric analysis of the
      tested compounds showed an increase in the number of apoptotic cells in a dose
      dependent manner. The further mechanistic study demonstrated that 1, 2, 4
      triazole-chalcone hybrids induced apoptosis via increased level of proapoptotic
      protein Bax, release of cytochrome c from mitochondria and activation of caspase
      3/8/9 proteins. However, general caspase inhibition by the pan-caspase inhibitor,
      z-VAD-fmk, significantly decreased the apoptosis induced by the tested hybrids,
      suggesting dependency of apoptosis on activation of the caspase-3 pathway.

PMID- 29660691
TI  - Proteomic Analysis of Liquid Biopsy from Tumor-Draining Vein Indicates that High
      Expression of Exosomal ECM1 Is Associated with Relapse in Stage I-III Colon
      Cancer.
AB  - BACKGROUND: The analysis of exosomes in blood obtained from the tumor-draining
      mesenteric vein (MV) can identify tumor biomarkers before they reach target
      organs and form the premetastatic niche where circulating tumor cells can anchor.
      Our group has recently shown that microRNAs in plasma from the MV-but not the
      peripheral vein (PV)-have been related to liver metastases in colon cancer (CC)
      patients. Here we examine the exosomal protein cargo in plasma from the MV and
      paired PV in 31 CC patients. PATIENTS AND METHODS: The study included patients
      who were initially diagnosed with stage I-III CC and 10 healthy controls.
      Exosomes from the MV and PV of all patients and controls were isolated by
      ultracentrifugation and confirmed by cryogenic transmission electron microscopy.
      High-throughput proteomic analysis by mass spectrometry was used to identify
      expression levels of exosomal proteins. Findings were confirmed by Western blot.
      RESULTS: Exosomal ECM1 protein was more highly expressed in patients than in
      controls and was 13.55 times higher in MV from relapsed than relapse-free
      patients. High exosomal ECM1 expression was associated with liver metastases.
      Patients with high exosomal ECM1 expression in MV-but not PV-plasma had shorter
      time to relapse than those with low ECM1 expression (P = .04). CONCLUSION: High
      levels of exosomal ECM1 protein can identify CC patients with a higher risk of
      relapse. The analysis of exosomes isolated from the tumor-draining MV is a
      promising method for the identification of biomarkers before they reach the
      target organ.

PMID- 29660693
TI  - The partial root-zone saline irrigation system and antioxidant responses in
      tomato plants.
AB  - Salinity is a limiting factor that can affect plant growth and cause significant
      losses in agricultural productivity. This study provides an insight about the
      viability of partial root-zone irrigation (PRI) system with saline water
      supported by a biochemical approach involving antioxidant responses. Six
      different irrigation methods using low and high salt concentrations (S1-0.5 and
      S2-5.0 dS m-1) were applied, with or without PRSI, so that one side of the root
      zone was submitted to saline water while the other side was low salinity water
      irrigated. The results revealed different responses according to the treatments
      and the PRSI system applied. For the treatments T1, T2 and T3, the PRSI was not
      applied, while T4, T5 and T6 treatments were applied with PRSI system. Lipid
      peroxidation, proline content, and activities of SOD, CAT, APX, GR and GSH in
      tomato plants subjected to PRSI system were analyzed. Plant growth was not
      affected by the salt concentrations; however, plants submitted to high salt
      concentrations showed high MDA content and Na+ accumulation when compared to the
      control plants. Plants submitted to treatments T4, T5 and T6 with PRSI system
      exhibited lower MDA compared to the control plants (T1). Proline content and
      activities of SOD, CAT, APX, GR and GSH content were maintained in all treatments
      and tissues analyzed, with only exception for APX in fruits and GSH content, in
      roots. The overall results showed that PRSI system could be an applicable
      technique for saline water supply on irrigation since plants did not show to be
      vulnerable to salt stress, supported by a biochemical approach involving
      antioxidant responses.

PMID- 29660692
TI  - Aggressive Phenotype of Cells Disseminated via Hematogenous and Lymphatic Route
      in Breast Cancer Patients.
AB  - Intratumoral heterogeneity of breast cancer remains a major challenge in
      successful treatment. Failure of cancer therapies can also be accredited to
      inability to systemically eradicate cancer stem cells (CSCs). Recent evidence
      points to the role of epithelial-mesenchymal transition (EMT) in expanding the
      pool of tumor cells with CSCs features. Thus, we assessed expression level as
      well as heterogeneity of CSCs markers in primary tumors (PT), lymph node
      metastasis (LNM), and circulating tumor cells (CTCs)-enriched blood fractions in
      order to correlate them with signs of EMT activation as well as
      clinicopathological data of breast cancer patients. Level of CSCs markers (ALDH1,
      CD44, CD133, OCT-4, NANOG) and EMT markers was quantified in PT (N=107), LNM
      (N=56), and CTCs-enriched blood fractions (N=85). Heterogeneity of CSCs markers
      expression within each PT and LNM was assessed by calculating Gini Index.
      Percentage of ALDH1-positive cells was elevated in PT in comparison to LNM (P =
      .005). However, heterogeneity of the four CSCs markers: ALDH1 (P = .019), CD133
      (P = .009), OCT-4 (P = .027), and CD44 (P < .001) was decreased in LNM. Samples
      classified as mesenchymal (post-EMT) showed elevated expression of CSCs markers
      (OCT-4 and CD44 in PT; OCT-4 in LNM; ALDH1, OCT-4, NANOG, CD44 in CTCs). Patients
      with mesenchymal-like CTCs had worse prognosis than patients with epithelial-like
      or no CTCs (P = .0025). CSCs markers are enriched in PT, LNM, and CTCs with
      mesenchymal features, but their heterogeneity is decreased in metastatic lymph
      nodes. Mesenchymal CTCs phenotype correlates with poor prognosis of the patients.

PMID- 29660694
TI  - The physiological effects of oil, dispersant and dispersed oil on the bay mussel,
      Mytilus trossulus, in Arctic/Subarctic conditions.
AB  - Increasing oil development around Alaska and other Arctic regions elevates the
      risk for another oil spill. Dispersants are used to mitigate the impact of an oil
      spill by accelerating natural degradation processes, but the reduced
      hydrophobicity of dispersed oil may increase its bioavailability to marine
      organisms. There is limited research on the effect of dispersed oil on cold water
      species and ecosystems. Therefore, spiked exposure tests were conducted with bay
      mussels (Mytilus trossulus) in seawater with non-dispersed oil, Corexit 9500 and
      oil dispersed with different concentrations of Corexit 9500. After three weeks of
      exposure, acute and chronic physiological impacts were determined. The majority
      of physiological responses occurred during the first seven days of exposure, with
      mussels exhibiting significant cytochrome P450 activity, superoxide dismutase
      activity and heat shock protein levels. Mussels exposed to non-dispersed oil also
      experienced immune suppression, reduced transcription and higher levels of
      mortality. After 21 days, mussels in all treatments exhibited evidence of genetic
      damage, tissue loss and a continued stress response. Bay mussels are useful as
      indicators of ecosystem health and recovery, and this study was an important step
      in understanding how non-dispersed oil, dispersant and dispersed oil affect the
      physiology of this sentinel species in Arctic/subarctic conditions.

PMID- 29660695
TI  - Metabolite profiles of striped marsh frog (Limnodynastes peronii) larvae exposed
      to the anti-androgenic fungicides vinclozolin and propiconazole are consistent
      with altered steroidogenesis and oxidative stress.
AB  - Amphibians use wetlands in urban and agricultural landscapes for breeding, growth
      and development. Fungicides and other pesticides used in these areas have
      therefore been identified as potential threats that could contribute towards
      amphibian population declines. However, relatively little is known about how such
      chemicals influence sensitive early life-stages or how short episodic exposures
      influence sub-lethal physiological and metabolic pathways. The present study
      applied untargeted metabolomics to evaluate effects in early post-hatch amphibian
      larvae exposed to the anti-androgenic fungicides vinclozolin and propiconazole.
      Recently hatched (Gosner developmental stage 25) striped marsh frog
      (Limnodynastes peronii) larvae were exposed for 96 h to vinclozolin at 17.5,
      174.8 and 1748.6 nM and propiconazole at 5.8, 58.4 and 584.4 nM. Nuclear Magnetic
      Resonance (NMR) spectroscopy was performed on polar metabolites obtained from
      whole-body extracts. Both fungicides altered metabolite profiles compared to
      control animals at all concentrations tested, and there were notable differences
      between the two chemicals. Overall responses were consistent with altered
      steroidogenesis and/or cholesterol metabolism, with inconsistent responses
      between the two fungicides likely reflecting minor differences in the mechanisms
      of action of these chemicals. Broad down-regulation of the tricarboxylic acid
      (TCA) cycle was also observed and is indicative of oxidative stress.
      Interestingly, formic acid was significantly increased in larvae exposed to
      vinclozolin but not propiconazole, suggesting this metabolite may serve as a
      useful biomarker of exposure to androgen-receptor binding anti-androgenic
      contaminants. This study demonstrates the power of untargeted metabolomics for
      distinguishing between similarly acting, but distinct, pollutants and for
      unraveling non-endocrine responses resulting from exposure to known endocrine
      active contaminants.

PMID- 29660697
TI  - Relapse to smoking following release from smoke-free correctional facilities in
      Queensland, Australia.
AB  - BACKGROUND: Smoke-free prison policies are increasingly common, but few studies
      have investigated relapse to smoking after release from prison. This study
      investigated return to tobacco smoking and correlates of smoking at reduced
      levels after release among adults recently released from smoke-free prisons in
      Queensland, Australia. METHODS: A cross-sectional survey of 114 people at parole
      offices within two months of release from prison was used. The survey measured
      health, social, and criminological factors related to tobacco smoking. We used
      logistic regression to identify factors associated with reduced post-release
      smoking levels compared to pre-incarceration levels. RESULTS: 94% of participants
      relapsed to smoking within two months of release; 72% relapsed on the day of
      release. 62% of participants smoked significantly less per day after compared
      with before incarceration. Living with a partner (Odds Ratio (OR) 2.77, 95%CI
      1.02-7.52), expressing support for smoke-free prison policies (OR 2.44, 95%CI
      1.12-5.32), intending to remain abstinent post-release (OR 4.29, 95%CI 1.88
      9.82), and intending to quit in the future (OR 3.88, 95%CI 1.66-9.07) were
      associated with reduced smoking post-release. Use of illicit drugs post-release
      was negatively associated with reduced smoking post-release (OR 0.27, 95%CI 0.09
      0.79). In multivariate analyses, pre-release intention to remain smoke-free was
      associated with reduced smoking post-release (AOR 2.69, 95%CI 1.01-7.14).
      DISCUSSION: Relapse to smoking after release from smoke-free prisons is common,
      but many who relapse smoke less than before incarceration, suggesting that smoke
      free prison policies may reduce post-release tobacco smoking. There is a need for
      tailored, evidence-based tobacco cessation interventions for people recently
      released from prison.

PMID- 29660696
TI  - Investigating the correlation between wastewater analysis and roadside drug
      testing in South Australia.
AB  - BACKGROUND: The societal impact of drug use is well known. An example is when
      drug-intoxicated drivers increase the burden on policing and healthcare services.
      METHODS: This work presents the correlation of wastewater analysis (using UHPLC
      MS/MS) and positive roadside drug testing results for methamphetamine, 3,4
      methylenedioxymethamphetamine (MDMA) and cannabis from December 2011-December
      2016 in South Australia. RESULTS: Methamphetamine and MDMA showed similar trends
      between the data sources with matching increases and decreases, respectively.
      Cannabis was relatively steady based on wastewater analysis, but the roadside
      drug testing data started to diverge in the final part of the measurement period.
      CONCLUSIONS: The ability to triangulate data as shown here validates both
      wastewater analysis and roadside drug testing. This suggests that changes in
      overall population drug use revealed by WWA is consistent and proportional with
      changes in drug-driving behaviours. The results show that, at higher levels of
      drug use as measured by wastewater analysis, there is an increase in drug driving
      in the community and therefore more strain on health services and police.

PMID- 29660698
TI  - Bacterial community succession and degradation patterns of hydrocarbons in
      seawater at low temperature.
AB  - The risk of oil spills in cold marine environments is expected to increase in
      response to trans-Arctic shipping and as Arctic oil reserves get exploited.
      Marine hydrocarbon-degrading microbes can reduce the impact of spilled
      hydrocarbons, but their degradation capabilities at low temperature are yet to be
      uncovered. We combined DNA amplicon sequencing and chemometrics to investigate
      the effect of decreasing temperature (0-15  degrees C) on the succession and
      function of hydrocarbon-degrading bacteria in seawater. The bacterial community
      and degradation patterns were investigated at time points when a similar amount
      of hydrocarbons was mineralised at the different temperatures. This allowed
      decomposing the effect of temperature into a main component related to the
      reduced microbial activity at low temperature and a secondary effect. The reduced
      microbial activity at low temperature delayed the microbial community succession
      and degradation rates. The secondary effect of temperature was most pronounced at
      0  degrees C, where (1) degradation of the least water-soluble n-alkanes (>C12)
      was suppressed in contrast to a relative stronger degradation of the most water
      soluble n-alkanes (<C12) and polycyclic aromatic hydrocarbons; and (2) bacterial
      taxa which we identified as psychrosensitive were inhibited, whereas taxa
      identified as psychrophilic flourished.

PMID- 29660699
TI  - A new model for simulating microbial cyanide production and optimizing the medium
      parameters for recovering precious metals from waste printed circuit boards.
AB  - Bioleaching is a green recycling technology for recovering precious metals from
      waste printed circuit boards (WPCBs). However, this technology requires
      increasing cyanide production to obtain desirable recovery efficiency. Luria
      Bertani medium (LB medium, containing tryptone 10 g/L, yeast extract 5 g/L, NaCl
      10 g/L) was commonly used in bioleaching of precious metal. In this study,
      results showed that LB medium did not produce highest yield of cyanide. Under
      optimal culture conditions (25  degrees C, pH 7.5), the maximum cyanide yield of
      the optimized medium (containing tryptone 6 g/L and yeast extract 5 g/L) was 1.5
      times as high as that of LB medium. In addition, kinetics and relationship of
      cell growth and cyanide production was studied. Data of cell growth fitted
      logistics model well. Allometric model was demonstrated effective in describing
      relationship between cell growth and cyanide production. By inserting logistics
      equation into allometric equation, we got a novel hybrid equation containing five
      parameters. Kinetic data for cyanide production were well fitted to the new
      model. Model parameters reflected both cell growth and cyanide production
      process.

PMID- 29660700
TI  - Responses of bacterial community to dibutyl phthalate pollution in a soil
      vegetable ecosystem.
AB  - Phthalate esters (PAEs) are a type of plasticizer that has aroused great concern
      due to their mutagenic, teratogenic, and carcinogenic effects, wherefore dibutyl
      phthalate (DBP) and other PAEs have been listed as priority pollutants. In this
      study, the impacts of DBP on a soil-vegetable ecosystem were investigated. The
      results showed that DBP could accumulate within vegetable tissues, and the
      accumulative effect was enhanced with higher levels of DBP contamination in
      soils. DBP accumulation also decreased vegetable quality in various ways,
      including decreased soluble protein content and increased nitrate content. The
      diversity of bacteria in soils gradually decreased with increasing DBP
      concentration, while no clear association with endophytic bacteria was observed.
      Also, the relative abundance, structure, and composition of soil bacterial
      communities underwent successional change during the DBP degradation period. The
      variation of bulk soil bacterial community was significantly associated with DBP
      concentration, while changes in the rhizosphere soil bacteria community were
      significantly associated with the properties of both soil and vegetables. The
      results indicated that DBP pollution could increase the health risk from
      vegetables and alter the biodiversity of indigenous bacteria in soil-vegetable
      ecosystems, which might further alter ecosystem functions in agricultural fields.

PMID- 29660701
TI  - Efficient detection of hazardous catechol and hydroquinone with MOF-rGO modified
      carbon paste electrode.
AB  - Reduced graphite oxide (rGO) was incorporated into a metal organic framework
      (MOF) MIL-101(Cr) for the modification of carbon paste electrode. Taking
      advantages of the large surface area of MOF and the electrical conductivity of
      rGO, the resulted electrodes exhibited high sensitivity and reliability in the
      simultaneous electrochemical identification and quantification of catechol (CC)
      and hydroquinone (HQ). Specifically, in the mixture solution of catechol and
      hydroquinone (constant concentration of an analyte), the linear response ranges
      for catechol and hydroquinone were 10-1400 MUM and 4-1000 MUM, and detection
      limits were 4 MUM and 0.66 MUM (S/N = 3) for individual catechol and
      hydroquinone, respectively. Therefore, the relatively easy fabrication of
      modified CPE and its fascinating reliability towards HQ and CC detection may
      simulate more research interest in the applications of MIL-101(Cr)-rGO composites
      for electrochemical sensors.

PMID- 29660702
TI  - A suspected case of coronary vasospasm induced by anaphylactic shock caused by
      rocuronium-sugammadex complex.

PMID- 29660703
TI  - Fungal bioleaching of WPCBs using Aspergillus niger: Observation, optimization
      and kinetics.
AB  - In this study, Aspergillus niger (A. niger) as an environmentally friendly agent
      for fungal bioleaching of waste printed circuit boards (WPCBs) was employed. D
      optimal response surface methodology (RSM) was utilized for optimization of the
      bioleaching parameters including bioleaching method (one step, two step and spent
      medium) and pulp densities (0.5 g L-1 to 20 g L-1) to maximize the recovery of
      Zn, Ni and Cu from WPCBs. According to the high performance liquid chromatography
      analysis, citric, oxalic, malic and gluconic acids were the most abundant organic
      acids produced by A.niger in 21 days experiments. Maximum recoveries of 98.57% of
      Zn, 43.95% of Ni and 64.03% of Cu were achieved based on acidolysis and
      complexolysis dissolution mechanisms of organic acids. Based on the kinetic
      studies, the rate controlling mechanism for Zn dissolution at one step approach
      was found to be diffusion through liquid film, while it was found to be mixed
      control for both two step and spent medium. Furthermore, rate of Cu dissolution
      which is controlled by diffusion in one step and two step approaches, detected to
      be controlled by chemical reaction at spent medium. It was shown that for Ni, the
      rate is controlled by chemical reaction for all the methods studied. Eventually,
      it was understood that A. niger is capable of leaching 100% of Zn, 80.39% of Ni
      and 85.88% of Cu in 30 days.

PMID- 29660704
TI  - Influence of food waste addition over microbial communities in an Anaerobic
      Membrane Bioreactor plant treating urban wastewater.
AB  - Notorious changes in microbial communities were observed during and after the
      joint treatment of wastewater with Food Waste (FW) in an Anaerobic Membrane
      Bioreactor (AnMBR) plant. The microbial population was analysed by high
      throughput sequencing of the 16S rRNA gene and dominance of Chloroflexi,
      Firmicutes, Synergistetes and Proteobacteria phyla was found. The relative
      abundance of these potential hydrolytic phyla increased as a higher fraction of
      FW was jointly treated. Moreover, whereas Specific Methanogenic Activity (SMA)
      rose from 10 to 51 mL CH4 g-1 VS, Methanosarcinales order increased from 34.0%
      over 80.0% of total Archaea, being Methanosaeta the dominant genus. The effect of
      FW over AnMBR biomass was observed during the whole experience, as methane
      production rose from 49.2 to 144.5 L CH4 . kg-1 influent COD. Furthermore,
      biomethanization potential was increased over 82% after the experience. AnMBR
      technology allows the established microbial community to remain in the bioreactor
      even after the addition of FW, improving the anaerobic digestion of urban
      wastewater.

PMID- 29660705
TI  - Enhancement of volatile fatty acid production and biogas yield from food waste
      following sonication pretreatment.
AB  - The positive effect of sonication on volatile fatty acid (VFA) and hydrogen
      production was investigated by batch experiments. Several sonication densities
      (2, 1.6, and 1.2 W/mL) and times (5, 10, and 15 min) were tested. The optimal
      sonication condition was ultrasonic density 2 W/mL and ultrasonic time 15 min (2
      U15). The FW particle size larger than 50 MUm (d > 50 MUm) were more susceptible
      to the sonication treatment than the smaller particle size (d <= 50 MUm). The
      SCOD increased and VS reduction accelerated under sonication treatment. The
      maximum VFA production and the highest proportion of hydrogen in the biogas
      increased 65.3% and 59.1%, respectively, under the optimal sonication conditions
      compared to the unsonicated batch. Moreover, a reduction of over 50% in the time
      required to reach its maximum production was also observed. Butyric acid
      fermentation type was obtained whether following sonication treatment or not. The
      composition of key microbial community differed under the various sonication
      conditions. The genera Clostridium and Parabacteroides are predominantly
      responsible for VFA generation and both were found to be abundant under the
      optimal condition.

PMID- 29660706
TI  - Evaluation of SnO2 for sunlight photocatalytic decontamination of water.
AB  - The broad bandgap tin (IV) oxide (SnO2) is the least investigated semiconductor
      material for photocatalytic water decontamination in sunlight exposure. A
      detailed study covering the synthesis, characterization and the evaluation of
      photocatalytic activity of SnO2, in the natural sunlight exposure, is presented.
      The structural characterization by XRD revealed the formation of phase pure
      tetragonal SnO2 with the average crystallite size of ~41.5 nm whereas minor Sn2+
      states in the material were identified by XPS analysis. As explored by diffuse
      reflectance (DR) and photoluminescence (PL) spectroscopy, the material exhibited
      a distinct absorption edge at ~3.4 eV. The morphological and microstructure
      analysis of the synthesized SnO2 was carried out by FESEM and HRTEM. The
      electrochemical impedance spectroscopy (EIS) and chronopotentiometry (CP)
      predicted the better charge transport and retention ability of the material under
      illumination whereas the Mott-Schottky extrapolation prophesied the n-type
      behavior with the flat-band potential of -0.60 V. The photocatalytic activity of
      SnO2 was assessed in the exposure of complete spectrum natural sunlight for the
      removal of 2,4,6-trichlorophenol. The HPLC and TOC analysis monitored the
      progress of degradation and mineralization whereas the released chloride ions
      were evaluated by ion chromatography. The effect of the transition metal ions
      (Fe3+, Cu2+, Ni2+, and Zn2+) as electron capture agents and H2O2 as ROS generator
      was explored during the degradation process. The utility of the material for the
      simultaneous removal of chlorophenols in the mixture was also investigated. The
      SnO2 exhibited sustained activity in the repeated use. Based on experimental
      evidence congregated, the mechanism of the removal process and the efficacy of
      SnO2 for sunlight photocatalytic decontamination of water was established.

PMID- 29660707
TI  - Source apportionment studies on particulate matter (PM10 and PM2.5) in ambient
      air of urban Mangalore, India.
AB  - Particulate matter (PM10 and PM2.5) samples were collected from six sites in
      urban Mangalore and the mass concentrations for PM10 and PM2.5 were measured
      using gravimetric technique. The measurements were found to exceed the national
      ambient air quality standards (NAAQS) limits, with the highest concentration of
      231.5 MUg/m3 for PM10 particles at Town hall and 120.3 MUg/m3 for PM2.5 particles
      at KMC Attavar. The elemental analysis using inductively coupled plasma optical
      emission spectrophotometer (ICPOES) revealed twelve different elements (As, Ba,
      Cd, Cr, Cu, Fe, Mg, Mn, Mo, Ni, Sr and Zn) for PM10 particles and nine different
      elements (Ba, Cd, Cr, Cu, Fe, Mn, Ni, Pb, Sr and Zn) for PM2.5 particles.
      Similarly, ionic composition of these samples measured by ion chromatography (IC)
      divulged nine different ions (F-, Cl-, NO3-, PO43-, SO42-, Na+, K+, Mg2+ and
      Ca2+) for PM10 particles and ten different ions (F-, Cl-, NO3-, PO43-, SO42-,
      Na+, NH4+, K+, Mg2+ and Ca2+) for PM2.5 particles. The source apportionment study
      of PM10 and PM2.5 for urban Mangalore in accordance with these six sample sites
      using chemical mass balance model (CMBv8.2) revealed nine and twelve predominant
      contributors for both PM10 and PM2.5, respectively. The highest contributor of
      PM10 was found to be paved road dust followed by diesel and gasoline vehicle
      emissions. Correspondingly, PM2.5 was found to be contributed mainly from two
      wheeler vehicle emissions followed by four-wheeler and heavy vehicle emissions
      (diesel vehicles). The current study depicts that the PM10 and PM2.5 in ambient
      air of Mangalore region has 70% of its contribution from vehicular emissions
      (both exhaust and non-exhaust).

PMID- 29660708
TI  - The role of COD/N ratio on the start-up performance and microbial mechanism of an
      upflow microaerobic reactor treating piggery wastewater.
AB  - This study investigated the role of COD/N ratio on the start-up and performance
      of an upflow microaerobic sludge reactor (UMSR) treating piggery wastewater at
      0.5 mgO2/L. At high COD/N ratio (6.24 and 4.52), results showed that the
      competition for oxygen between ammonia-oxidizing bacteria, nitrite-oxidizing
      bacteria and heterotrophic bacteria limited the removal of nitrogen. Nitrogen
      removal efficiency was below 40% in both scenarios. Decreasing the influent COD/N
      ratio to 0.88 allowed achieving high removal efficiencies for COD (~75%) and
      nitrogen (~85%) due to the lower oxygen consumption for COD mineralization.
      Molecular biology techniques showed that nitrogen conversion at a COD/N ratio
      0.88 was dominated by the anammox pathway and that Candidatus Brocadia sp. was
      the most important anammox bacteria in the reactor with a relative abundance of
      58.5% among the anammox bacteria. Molecular techniques also showed that
      Nitrosomonas spp. was the major ammonia-oxidiser bacteria (relative abundance of
      86.3%) and that denitrification via NO3- and NO2- also contributed to remove
      nitrogen from the system.

PMID- 29660709
TI  - A simplified approach to determine the carbon footprint of a region: Key learning
      points from a Galician study.
AB  - On a previous study, the carbon footprint (CF) of all production and consumption
      activities of Galicia, an Autonomous Community located in the north-west of
      Spain, was determined and the results were used to devise strategies aimed at the
      reduction and mitigation of the greenhouse gas (GHG) emissions. The territorial
      LCA methodology was used there to perform the calculations. However, that
      methodology was initially designed to compute the emissions of all types of
      polluting substances to the environment (several thousands of substances
      considered in the life cycle inventories), aimed at performing complete LCA
      studies. This requirement implies the use of specific modelling approaches and
      databases that in turn raised some difficulties, i.e., need of large amounts of
      data (which increased gathering times), low temporal, geographical and
      technological representativeness of the study, lack of data, and presence of
      double counting issues when trying to combine the sectorial CF results into those
      of the total economy. In view of these of difficulties, and considering the need
      to focus only on GHG emissions, it seems important to improve the robustness of
      the CF computation while proposing a simplified methodology. This study is the
      result of those efforts to improve the aforementioned methodology. In addition to
      the territorial LCA approach, several Input-Output (IO) based alternatives have
      been used here to compute direct and indirect GHG emissions of all Galician
      production and consumption activities. The results of the different alternatives
      were compared and evaluated under a multi-criteria approach considering
      reliability, completeness, temporal and geographical correlation, applicability
      and consistency. Based on that, an improved and simplified methodology was
      proposed to determine the CF of the Galician consumption and production
      activities from a total responsibility perspective. This methodology adequately
      reflects the current characteristics of the Galician economy, thus increasing the
      representativeness of the results, and can be applied to any region in which IO
      tables and environmental vectors are available. This methodology could thus
      provide useful information in decision making processes to reduce and prevent GHG
      emissions.

PMID- 29660710
TI  - Advances in algal-prokaryotic wastewater treatment: A review of nitrogen
      transformations, reactor configurations and molecular tools.
AB  - The synergistic activity of algae and prokaryotic microorganisms can be used to
      improve the efficiency of biological wastewater treatment, particularly with
      regards to nitrogen removal. For example, algae can provide oxygen through
      photosynthesis needed for aerobic degradation of organic carbon and nitrification
      and harvested algal-prokaryotic biomass can be used to produce high value
      chemicals or biogas. Algal-prokaryotic consortia have been used to treat
      wastewater in different types of reactors, including waste stabilization ponds,
      high rate algal ponds and closed photobioreactors. This review addresses the
      current literature and identifies research gaps related to the following topics:
      1) the complex interactions between algae and prokaryotes in wastewater
      treatment; 2) advances in bioreactor technologies that can achieve high nitrogen
      removal efficiencies in small reactor volumes, such as algal-prokaryotic biofilm
      reactors and enhanced algal-prokaryotic treatment systems (EAPS); 3) molecular
      tools that have expanded our understanding of the activities of algal and
      prokaryotic communities in wastewater treatment processes.

PMID- 29660711
TI  - The rhizosphere microbiome: Significance in rhizoremediation of polyaromatic
      hydrocarbon contaminated soil.
AB  - Microbial communities are an essential part of plant rhizosphere and participate
      in the functioning of plants, including rhizoremediation of petroleum
      contaminants. Rhizoremediation is a promising technology for removal of
      polyaromatic hydrocarbons based on interactions between plants and microbiome in
      the rhizosphere. Root exudation in the rhizosphere provides better nutrient
      uptake for rhizosphere microbiome, and therefore it is considered to be one of
      the major factors of microbial community function in the rhizosphere that plays a
      key role in the enhanced PAH biodegradation. Although the importance of the
      rhizosphere microbiome for plant growth has been widely recognized, the
      interactions between microbiome and plant roots in the process of rhizosphere
      mediated remediation of PAH still needs attention. Most of the current researches
      target PAH degradation by plant or single microorganism, separately, whereas the
      interactions between plants and whole microbiome are overlooked and its role has
      been ignored. This review summarizes recent knowledge of PAH degradation in the
      rhizosphere in the process of plant-microbiome interactions based on emerging
      omics approaches such as metagenomics, metatranscriptomics, metabolomics and
      metaproteomics. These omics approaches with combinations to bioinformatics tools
      provide us a better understanding in integrated activity patterns between plants
      and rhizosphere microbes, and insight into the biochemical and molecular
      modification of the meta-organisms (plant-microbiome) to maximize
      rhizoremediation activity. Moreover, a better understanding of the interactions
      could lead to the development of techniques to engineer rhizosphere microbiome
      for better hydrocarbon degradation.

PMID- 29660712
TI  - Long-run operation of a reverse electrodialysis system fed with wastewaters.
AB  - The performance of a Reverse ElectroDialysis (RED) system fed by unconventional
      wastewater solutions for long operational periods is analysed for the first time.
      The experimental campaign was divided in a series of five independent long-runs
      which combined real wastewater solutions with artificial solutions for at least
      10 days. The time evolution of electrical variables, gross power output and net
      power output, considering also pumping losses, was monitored: power density
      values obtained during the long-runs are comparable to those found in literature
      with artificial feed solutions of similar salinity. The increase in pressure
      drops and the development of membrane fouling were the main detrimental factors
      of system performance. Pressure drops increase was related to the physical
      obstruction of the feed channels defined by the spacers, while membrane fouling
      was related to the adsorption of foulants over the membrane surfaces. In order to
      manage channels partial clogging and fouling, different kinds of easily
      implemented in situ backwashings (i.e. neutral, acid, alkaline) were adopted,
      without the need for an abrupt interruption of the RED unit operation. The
      application of periodic ElectroDialysis (ED) pulses is also tested as fouling
      prevention strategy. The results collected suggest that RED can be used to
      produce electric power by unworthy wastewaters, but additional studies are still
      needed to characterize better membrane fouling and further improve system
      performance with these solutions.

PMID- 29660713
TI  - Assessment of climate change impact on yield of major crops in the Banas River
      Basin, India.
AB  - Crop growth models like AquaCrop are useful in understanding the impact of
      climate change on crop production considering the various projections from global
      circulation models and regional climate models. The present study aims to assess
      the climate change impact on yield of major crops in the Banas River Basin i.e.,
      wheat, barley and maize. Banas basin is part of the semi-arid region of Rajasthan
      state in India. AquaCrop model is used to calculate the yield of all the three
      crops for a historical period of 30years (1981-2010) and then compared with
      observed yield data. Root Mean Square Error (RMSE) values are calculated to
      assess the model accuracy in prediction of yield. Further, the calibrated model
      is used to predict the possible impacts of climate change and CO2 concentration
      on crop yield using CORDEX-SA climate projections of three driving climate models
      (CNRM-CM5, CCSM4 and MPI-ESM-LR) for two different scenarios (RCP4.5 and RCP8.5)
      for the future period 2021-2050. RMSE values of simulated yield with respect to
      observed yield of wheat, barley and maize are 11.99, 16.15 and 19.13,
      respectively. It is predicted that crop yield of all three crops will increase
      under the climate change conditions for future period (2021-2050).

PMID- 29660714
TI  - Techno-environmental assessment of the green biorefinery concept: Combining
      process simulation and life cycle assessment at an early design stage.
AB  - The Green biorefinery (GBR) is a biorefinery concept that converts fresh biomass
      into value-added products. The present study combines a Process Flowsheet
      Simulation (PFS) and Life Cycle Assessment (LCA) to evaluate the technical and
      environmental performance of different GBR configurations and the cascading
      utilization of the GBR output. The GBR configurations considered in this study,
      test alternatives in the three main steps of green-biorefining: fractionation,
      precipitation, and protein separation. The different cascade utilization
      alternatives analyse different options for press-pulp utilization, and the LCA
      results show that the environmental profile of the GBR is highly affected by the
      utilization of the press-pulp and thus by the choice of conventional product
      replaced by the press-pulp. Furthermore, scenario analysis of different GBR
      configurations shows that higher benefits can be achieved by increasing product
      yields rather than lowering energy consumption. Green biorefining is shown to be
      an interesting biorefining concept, especially in a Danish context. Biorefining
      of green biomass is technically feasible and can bring environmental savings,
      when compared to conventional production methods. However, the savings will be
      determined by the processing involved in each conversion stage and on the cascade
      utilization of the different platform products.

PMID- 29660715
TI  - Characterization of the emissions impacts of hybrid excavators with a portable
      emissions measurement system (PEMS)-based methodology.
AB  - Hybrid engine technology is a potentially important strategy for reduction of
      tailpipe greenhouse gas (GHG) emissions and other pollutants that is now being
      implemented for off-road construction equipment. The goal of this study was to
      evaluate the emissions and fuel consumption impacts of electric-hybrid excavators
      using a Portable Emissions Measurement System (PEMS)-based methodology. In this
      study, three hybrid and four conventional excavators were studied for both real
      world activity patterns and tailpipe emissions. Activity data was obtained using
      engine control module (ECM) and global positioning system (GPS) logged data,
      coupled with interviews, historical records, and video. This activity data was
      used to develop a test cycle with seven modes representing different types of
      excavator work. Emissions data were collected over this test cycle using a PEMS.
      The results indicated the HB215 hybrid excavator provided a significant reduction
      in tailpipe carbon dioxide (CO2) emissions (from -13 to -26%), but increased
      diesel particulate matter (PM) (+26 to +27%) when compared to a similar model
      conventional excavator over the same duty cycle.

PMID- 29660716
TI  - High time-resolution simulation of E. coli on hands reveals large variation in
      microbial exposures amongst Vietnamese farmers using human excreta for
      agriculture.
AB  - Infectious disease transmission is frequently mediated by the environment, where
      people's movements through and interactions with the environment dictate risks of
      infection and/or illness. Capturing these interactions, and quantifying their
      importance, offers important insights into effective interventions. In this
      study, we capture high time-resolution activity data for twenty-five Vietnamese
      farmers during collection and land application of human excreta for agriculture.
      Although human excreta use improves productivity, the use increases risks of
      enteric infections for both farmers and end users. In our study, the activity
      data are integrated with environmental microbial sampling data into a stochastic
      mechanistic simulation of E. coli contamination on hands and E. coli ingested.
      Results from the study include frequent and variable contact rates for farmers'
      hands (from 34 to 1344 objects contacted per hour per hand), including highly
      variable hand-to-mouth contact rates (from 0 to 9 contacts per hour per hand).
      The frequency of hand-to-mouth contacts was substantially lower than the widely
      used frequency previously reported for U.S. Office Workers. Environmental
      microbial contamination data highlighted ubiquitous E. coli contamination in the
      environment, including excreta, hands, toilet pit, handheld tools, soils,
      surfaces, and water. Results from the simulation suggest dynamic changes in E.
      coli contamination on hands, and wide variation in hand contamination and E. coli
      ingested amongst the farmers studied. Sensitivity analysis suggests that E. coli
      contamination on hands and ingested doses are most influenced by contamination of
      handheld tools, excreta, and the toilet pit as well as by frequency of hand-to
      mouth contacts. The study findings are especially relevant given the context: no
      farmers reported adequate storage time of human excreta, and personal protective
      mask availability did not prevent hand-to-mouth contacts. Integrating high time
      resolution activity data into exposure assessments highlights variation in
      exposures amongst farmers, and offers greater insight into effective
      interventions and their potential impacts.

PMID- 29660717
TI  - Agricultural conservation practices can help mitigate the impact of climate
      change.
AB  - Agricultural conservation practices (CPs) are commonly implemented to reduce
      diffuse nutrient pollution. Climate change can complicate the development,
      implementation, and efficiency of agricultural CPs by altering hydrology,
      nutrient cycling, and erosion. This research quantifies the impact of climate
      change on hydrology, nutrient cycling, erosion, and the effectiveness of
      agricultural CP in the Susquehanna River Basin in the Chesapeake Bay Watershed,
      USA. We develop, calibrate, and test the Soil and Water Assessment Tool-Variable
      Source Area (SWAT-VSA) model and select four CPs; buffer strips, strip-cropping,
      no-till, and tile drainage, to test their effectiveness in reducing climate
      change impacts on water quality. We force the model with six downscaled global
      climate models (GCMs) for a historic period (1990-2014) and two future scenario
      periods (2041-2065 and 2075-2099) and quantify the impact of climate change on
      hydrology, nitrate-N (NO3-N), total N (TN), dissolved phosphorus (DP), total
      phosphorus (TP), and sediment export with and without CPs. We also test
      prioritizing CP installation on the 30% of agricultural lands that generate the
      most runoff (e.g., critical source areas-CSAs). Compared against the historical
      baseline and with no CPs, the ensemble model predictions indicate that climate
      change results in annual increases in flow (4.5+/-7.3%), surface runoff (3.5+/
      6.1%), sediment export (28.5+/-18.2%) and TN export (9.5+/-5.1%), but decreases
      in NO3-N (12+/-12.8%), DP (14+/-11.5), and TP (2.5+/-7.4%) export. When
      agricultural CPs are simulated most do not appreciably change the water balance,
      however, tile drainage and strip-cropping decrease surface runoff, sediment
      export, and DP/TP, while buffer strips reduce N export. Installing CPs on CSAs
      results in nearly the same level of performance for most practices and most
      pollutants. These results suggest that climate change will influence the
      performance of agricultural CPs and that targeting agricultural CPs to CSAs can
      provide nearly the same level of water quality effects as more widespread
      adoption.

PMID- 29660718
TI  - Seasonal variations of steroid hormones released by wastewater treatment plants
      to river water and sediments: Distribution between particulate and dissolved
      phases.
AB  - Extensive environmental monitoring was conducted in an urban river impacted by
      multiple combined sewer overflows (CSOs) and wastewater treatment plant (WWTP)
      discharge points. Temporal and spatial distributions of dissolved and particulate
      steroids (progesterone (Prog), testosterone (Testo), medroxyprogesterone (MDRXY
      Prog), levonorgestrel (Levo), norethindrone (Nore), estrone (E1), estradiol (E2),
      estriol (E3), and 17alpha-ethinylestradiol (EE2)) were investigated in sewage,
      WWTP effluents, receiving river water and sediments, and in drinking water plant
      (DWP) intakes. Steroids were detected in both dissolved and particulate phases
      with mean concentrations from 21ngL-1 to 389ngL-1 in raw sewage and from 10ngL-1
      to 296ngL-1 in treated wastewater. The particle-associated steroids represented 0
      82% of their total concentration as some steroids like E1 and E3 were detected
      only in the dissolved phase while MDRXY-Prog (81%), Nore (71%), and EE2 (>75%)
      were primarily detected in the particulate phase. Particle-associated steroids
      were detected in spring samples from river water with mean concentrations ranging
      from 5.4ngL-1 to 35.7ngL-1 compare to 3ngL-1 to 6.8ngL-1 in summer samples.
      Levels of particle-associated Testo, Nore, E2 and Levo in DWP intakes (406.2
      13,149.1ngg-1) were similar to those found in raw sewage (336.6-7628.8ngg-1),
      indicating their persistence in the suspended phase from discharge points. Total
      steroids measured in sediments were in the range of 7-1213ngg-1, 5-25ngg-1, and
      22-226ngg-1 in autumn, spring, and summer, respectively. Our findings confirm the
      presence and seasonal variation of a mixture of particle-associated steroids in
      drinking water sources. The presence of high concentrations of a mixture of
      particle-associated steroids in DWP intakes highlight the need for highly
      effective particle-removal processes to eliminate these recalcitrant compounds
      during drinking water production. Finally, the detected concentrations raise
      concerns about their potential environmental effects.

PMID- 29660719
TI  - Assessment of endocrine disruptors effects on zebrafish (Danio rerio) embryos by
      untargeted LC-HRMS metabolomic analysis.
AB  - Bisphenol A (BPA), perfluorooctane sulfonate (PFOS), and tributyltin (TBT) are
      emerging endocrine disruptors (EDCs) with still poorly defined mechanisms of
      toxicity and metabolic effects in aquatic organisms. We used an untargeted liquid
      chromatography-high resolution mass spectrometry (LC-HRMS) metabolomic approach
      to study the effects of sub-lethal doses of these three EDCs on the metabolic
      profiles of zebrafish embryos exposed from 48 to 120hpf (hours post
      fertilization). Advanced chemometric data analysis methods were used to reveal
      effects on the subjacent regulatory pathways. EDC treatments induced changes in
      concentrations of about 50 metabolites for TBT and BPA, and of 25 metabolites for
      PFOS. The analysis of the corresponding metabolic changes suggested the presence
      of similar underlying zebrafish responses to BPA, TBT and PFOS affecting the
      metabolism of glycerophospholipids, amino acids, purines and 2-oxocarboxylic
      acids. We related the changes in glycerophospholipid metabolism to alterations in
      absorption of the yolk sack, the main source of nutrients (including lipids) for
      the developing embryo, linking the molecular markers with adverse phenotypic
      effects. We propose a general mode of action for all three chemical compounds,
      probably related to their already described interaction with the PPAR/RXR
      complex, combined with specific effects on different signaling pathways resulting
      in particular alterations in the zebrafish embryos metabolism.

PMID- 29660720
TI  - Environmental impact of cheese production: A case study of a small-scale factory
      in southern Europe and global overview of carbon footprint.
AB  - The environmental performance of a small-scale cheese factory sited in a NW
      Spanish region has been analysed by Life Cycle Assessment (LCA) as representative
      of numerous cheese traditional factories that are scattered through the European
      Union, especially in the southern countries. Inventory data were directly
      obtained from this facility corresponding to one-year operation, and the main
      subsystems involved in cheese production were included, i.e. raw materials,
      water, electricity, energy, cleaning products, packaging materials, transports,
      solid and liquid wastes and gas emissions. Results indicated that the
      environmental impacts derived from cheese making were mainly originated from raw
      milk production and the natural land transformation was the most affected of the
      considered categories. On the contrary, the manufacturing of packaging material
      and other non-dairy ingredients barely influenced on the total impact.
      Additionally, an average carbon footprint of the cheeses produced in the analysed
      facility has also been calculated, resulting milk production and pellet boiler
      emissions the most contributing subsystems. Furthermore, it was notable the
      positive environmental effect that entailed the direct use of whey as animal
      feed, which was considered in this study as avoided fodder. Finally, a revision
      of published works regarding the environmental performance of cheese production
      worldwide was provided and compared to results found in the present work.
      According to the analysed data, it is clear that the content of fat and dry
      extract are determinant factors for the carbon footprint of cheeses, whereas the
      cheesemaking scale and the geographical area have a very low effect.

PMID- 29660721
TI  - Changes in soil water availability in vineyards can be traced by the carbon and
      nitrogen isotope composition of dried wines.
AB  - The grapevine is one of the most important edible fruit plants cultivated
      worldwide, and it is highly sensitive to changes in the soil water content. We
      studied the total carbon and nitrogen contents and stable isotope compositions
      (C/NWSR, delta13CWSR and delta15NWSR values) of the solid residues obtained by
      freeze-drying wines produced from two white grapevine cultivars (Vitis vinifera
      L. cv Chasselas and Petite Arvine) field grown under different soil water regimes
      while maintaining other climatic and ecopedological conditions identical. These
      experiments simulated the more frequent and extended climate change-induced
      periods of soil water shortage. The wines were from the 2009-2014 vintages,
      produced using the same vinification procedure. The plant water status,
      reflecting soil water availability, was assessed by the predawn leaf water
      potential (Psipd), monitored in the field during the growing seasons. For both
      wine varieties, the delta13CWSR values are highly correlated with Psipd values
      and record the soil water availability set by soil water holding capacity,
      rainfall and irrigation water supply. These relationships were the same as those
      observed for the carbon isotope composition of fruit sugars (i.e., must sugars)
      and plant water status. In Chasselas wines, the nitrogen content and delta15NWSR
      values decreased with soil water deficit, indicating control of the flux of soil
      water soluble nutrients into plants by soil water availability. Such a
      correlation was not found for Petite Arvine, probably due to different N
      metabolism processes in this genetically atypical cultivar. The results presented
      in this study confirm and generalize what was previously found for red wine
      (Pinot noir); the carbon isotope composition of wine solid residues is a reliable
      indicator of the soil and the plant water status and thus can be used to trace
      back local climatic conditions in the vineyard's region. In most wines (except
      Petite Arvine) the C/NWSR and delta15NWSR values are indicators of the origin of
      the nitrogen supplied to the plant's fruit (grape) that can be used to assess the
      N dynamics in the soil-water-plant system.

PMID- 29660722
TI  - Determinants of mercury contamination in viperine snakes, Natrix maura, in
      Western Europe.
AB  - The effects of Hg contamination are presumably widespread across the components
      of aquatic ecosystems, but investigations have been mainly focused on freshwater
      fish, because this biota represents a major source of Hg for human populations.
      Yet, the possible bioaccumulation of Hg on other freshwater meso- and apex
      predators (e.g., amphibians, reptiles) has been largely overlooked, especially in
      Western Europe. In this study, the determinants of Hg concentrations were
      assessed for the viperine snake (Natrix maura) across 6 populations (>130
      individuals sampled in 2016 and 2017) in France and Spain. Specifically, body
      size, sex, and diet were compared with Hg concentrations measured in ventral
      scales. Overall, N. maura accumulated Hg in their scales. Sex did not seem to
      influence Hg concentrations in this species. Significant differences in Hg
      concentrations were observed between study sites, and these differences were
      likely to be mediated by site-specific diet. Frog-eating individuals were
      characterized not only by lower mean values of Hg (0.194+/-0.018MUg.g-1 versus
      0.386+/-0.032MUg.g-1 for piscivorous individuals), but also by weaker slopes of
      the body size-Hg relationship as compared to fish-eating snakes, suggesting
      strong differences in accumulation rates due to food resources. Importantly, the
      highest slope of the body size-Hg relationship and the highest values of Hg were
      found in individuals foraging on trout raised by a fish farm, suggesting that
      fish farming may contribute to Hg contamination in inland freshwater systems.
      Finally, our results are compared with data on Hg concentrations in other species
      of aquatic snakes, in order to provide a comparative point for future studies.

PMID- 29660723
TI  - Fluoride prevalence in groundwater around a fluorite mining area in the flood
      plain of the River Swat, Pakistan.
AB  - This study investigated the fluoride (F-) concentrations and physicochemical
      parameters of the groundwater in a fluorite mining area of the flood plain region
      of the River Swat, with particular emphasis on the fate and distribution of F-
      and the hydrogeochemistry. To better understand the groundwater hydrochemical
      profile and F- enrichment, groundwater samples (n=53) were collected from shallow
      (24-40m), mid-depth (48-65m) and deep (85-120m) aquifers, and then analysed using
      an ion-selective electrode. The lowest F- concentration (0.7mg/L) was recorded in
      the deep-aquifer groundwater, while the highest (6.4mg/L) was recorded in shallow
      groundwater. Most groundwater samples (62.2%) exceeded the guideline (1.5mg/L)
      set by the World Health Organization (WHO); while for individual sources, 73% of
      shallow-groundwater samples (F- concentration up to 6.4mg/L), 42% of mid-depth
      groundwater samples, and 17% of deep-groundwater samples had F- concentrations
      that exceeded this permissible limit. Assessment of the overall quality of the
      groundwater revealed influences of the weathering of granite and gneisses rocks,
      along with silicate minerals and ion exchange processes. Hydrogeochemical
      analysis of the groundwater showed that Na+ is the dominant cation and HCO3- the
      major anion. The anionic and cationic concentrations across the entire study area
      increased in the following order: HCO3>SO4>Cl>NO3>F>PO4 and Na>Ca>Mg>K,
      respectively. Relatively higher F- toxicity levels were associated with the
      NaHCO3 water type, and the chemical facies were found to change from the CaHCO3
      to (NaHCO3) type in calcium-poor aquifers. Thermodynamic considerations of
      saturation indices indicated that fluorite minerals play a vital role in the
      prevalence of fluorosis, while under-saturation revealed that - besides fluorite
      minerals - other F- minerals that are also present in the region further increase
      the F- concentrations in the groundwater. Finally, a health risk assessment via
      Dean's classification method identified that the groundwater with relatively
      higher F- concentrations is unfit for drinking purposes.

PMID- 29660724
TI  - Influence of land urbanization on carbon sequestration of urban vegetation: A
      temporal cooperativity analysis in Guangzhou as an example.
AB  - Land urbanization can affect carbon sequestration. In this study, the
      relationships between land urbanization and carbon sequestration of urban
      vegetation were studied for Guangzhou, China. The methodology was based on land
      use data from Thematic Mapper (TM) imagery, MODIS13Q1 data, and climate data, and
      the improved Carnegie-Ames-Stanford approach (CASA) model and linear system
      models were employed. Characteristics such as the amount of expansion, spatial
      agglomeration, spatial expansion intensity, and spatial growth of built-up land
      were analyzed, and the influence of land urbanization (built-up land expansion)
      on carbon sequestration of urban vegetation was elucidated by a temporal
      sequential cooperativity analysis. The main results were as follows. (1) Land
      urbanization had a clear influence on carbon sequestration of urban vegetation in
      Guangzhou, and the proportion and spatial agglomeration of built-up land showed
      significant negative correlations with this carbon sequestration; the correlation
      coefficients were -0.443 and -0.537, respectively, in 2014. (2) The spatial
      expansion intensity and spatial growth of built-up land showed small correlations
      with carbon sequestration, and the correlations from 2000 to 2005 were relatively
      larger than those at other times; this was because the built-up land expansion
      speed was the fastest during this period. (3) The temporal sequential
      cooperativity analysis revealed that carbon was lost as natural surfaces were
      transformed to artificial surfaces, and land urbanization effects on carbon
      sequestration showed no significant temporal lag. Carbon sequestration of urban
      vegetation in the city could be improved by adding urban green spaces; however,
      this would likely take some time as the system recovers.

PMID- 29660725
TI  - Modeling lead concentration in drinking water of residential plumbing pipes and
      hot water tanks.
AB  - Drinking water is a potential source of exposure to lead (Pb), which can pose
      risk to humans. The regulatory agencies often monitor Pb in water treatment
      plants (WTP) and/or water distribution systems (WDS). However, people are exposed
      to tap water inside the house while water may stay in the plumbing premise for
      several hours prior to reaching the tap. Depending on stagnation period and
      plumbing premise, concentrations of Pb in tap water can be significantly higher
      than the WDS leading to higher intake of Pb than the values from WDS or WTP. In
      this study, concentrations of Pb and water quality parameters were investigated
      in WDS, plumbing pipe (PP) and hot water tanks (HWT) for 7months. The samples
      were collected and analyzed on bi-weekly basis for 7 times a day. Several linear,
      non-linear and neural network models were developed for predicting Pb in PP and
      HWT. The models were validated using the additional data, which were not used for
      model development. The concentrations of Pb in PP and HWT were 1-1.17 and 1-1.21
      times the Pb in WDS respectively. Concentrations of Pb were higher in summer than
      winter. The models showed moderate to excellent performance (R2=0.85-0.99) in
      predicting Pb in PP and HWT. The correlation coefficients (r) with the validation
      data were in the ranges of 0.76-0.90 and 0.97-0.99 for PP and HWT respectively.
      The models can be used for predicting Pb in tap water, which can assist to better
      protect the humans.

PMID- 29660726
TI  - The effect of chemical vapor deposition temperature on the performance of binder
      free sewage sludge-derived anodes in microbial fuel cells.
AB  - Conversion of sewage sludge (SS) into value-added material has garnered
      increasing attention due to its potential applications. In this study, we propose
      a new application of the sewage sludge-derived carbon (SSC) as an electrode
      without binder in microbial fuel cells (MFCs). SS was firstly converted into SSC
      monoliths by methane chemical vapor method at different temperature (600, 800,
      1000 or 1200 degrees C). Scanning electron microscopy images showed that carbon
      micro-wires were present on the surfaces of the samples prepared at 1000 and 1200
      degrees C. The results showed that it was beneficial for converting sludge into a
      highly conductive electrode and increasing carbon content of the electrode at
      higher temperatures, thereby improving the current generation. The conductivity
      results show that a higher temperature favors the conversion of sludge into a
      highly conductive electrode. The MFC using an SSC anode processed at 1200 degrees
      C generated the maximum power density of 2228mWm-2 and the maximum current
      density of 14.2Am-2. This value was 5 times greater than that generated by an MFC
      equipped with a graphite anode. These results present a promising means of
      converting SS into electrode materials.

PMID- 29660727
TI  - Effect of dissolved organic matter on pre-equilibrium passive sampling: A
      predictive QSAR modeling study.
AB  - : Pre-equilibrium passive sampling is a simple and promising technique for
      studying sampling kinetics, which is crucial to determine the distribution,
      transfer and fate of hydrophobic organic compounds (HOCs) in environmental water
      and organisms. Environmental water samples contain complex matrices that
      complicate the traditional calibration process for obtaining the accurate rate
      constants. This study proposed a QSAR model to predict the sampling rate
      constants of HOCs (polycyclic aromatic hydrocarbons (PAHs), polychlorinated
      biphenyls (PCBs) and pesticides) in aqueous systems containing complex matrices.
      A homemade flow-through system was established to simulate an actual aqueous
      environment containing dissolved organic matter (DOM) i.e. humic acid (HA) and (2
      Hydroxypropyl)-beta-cyclodextrin (beta-HPCD)), and to obtain the experimental
      rate constants. Then, a quantitative structure-activity relationship (QSAR) model
      using Genetic Algorithm-Multiple Linear Regression (GA-MLR) was found to
      correlate the experimental rate constants to the system state including
      physicochemical parameters of the HOCs and DOM which were calculated and selected
      as descriptors by Density Functional Theory (DFT) and Chem 3D. The experimental
      results showed that the rate constants significantly increased as the
      concentration of DOM increased, and the enhancement factors of 70-fold and 34
      fold were observed for the HOCs in HA and beta-HPCD, respectively. The
      established QSAR model was validated as credible (RAdj.2=0.862) and predictable
      (Q2=0.835) in estimating the rate constants of HOCs for complex aqueous sampling,
      and a probable mechanism was developed by comparison to the reported theoretical
      study. MAIN FINDING OF THE WORK: The present study established a QSAR model of
      passive sampling rate constants and calibrated the effect of DOM on the sampling
      kinetics.

PMID- 29660728
TI  - Corporate carbon footprint for country Climate Change mitigation: A case study of
      a tannery in Turkey.
AB  - Assessment of carbon emissions and environmental impact of production is
      indispensable to achieve a sustainable industrial production in Turkey,
      especially for those companies willing to compete in new international green
      markets. In this case study, corporate carbon footprint of a representative
      Turkish tanning company was analyzed. Inventory and impact data are presented to
      help in the environmental decision-making process. The results indicate that
      significant environmental impacts were caused during the landfilling of solid
      wastes as well as the production of the electricity and fuel required in the
      tannery. Turkish tannery inventory data presented here for the first time will be
      useful for leather tanning company managers to calculate sustainability key
      indicators. Improving alternatives at country level were identified (increasing
      the renewable sources on electricity production and promote energy recovery in
      landfills) which would be useful not only to decrease greenhouse gas (GHG)
      emissions of tanning sector but also of other industries requiring electricity
      and producing organic wastes. Considering the substantial contribution of
      industrial processes to the Turkish carbon emissions (15.7%) (TUIK, 2013), work
      done on those areas would provide a sound improvement in environmental profile of
      Turkey. The importance to promote a national strategy to reduce GHG emissions in
      Turkey was discussed here, as well as its relation to corporate carbon footprint
      assessments. One of the significant points revealed from the case study is the
      lack of published country specific emission factors for Turkey, which is a
      fundamental prerequisite to promote corporate carbon footprint assessment within
      the country.

PMID- 29660729
TI  - Biogas liquid digestate grown Chlorella sp. for biocrude oil production via
      hydrothermal liquefaction.
AB  - Microalgae can not only purify and recover the nutrients from wastewater, but
      also be harvested as wet biomass for the production of biocrude oil via
      hydrothermal liquefaction (HTL). Chlorella sp. cultivated in the ultrafiltration
      (UF) membrane treated anaerobic digestion (AD) liquid digestate of chicken manure
      was used as the feedstock in this study. The present study characterized the
      products and investigated the elemental migration during HTL of Chlorella sp. fed
      with AD effluent wastewater (WW) and BG11 standard medium (ST) in 100mL and 500mL
      reactors under different operational conditions. Results showed that the highest
      oil yield of WW (38.1%, daf) was achieved at 320 degrees C, 60min and 15% TS in
      500mL reactor, which was 14.1% higher than that of ST (33.4%, daf) at 320 degrees
      C, 30min and 20% TS in the same reactor. WW had a similar carbon and hydrogen
      distribution in the four product fractions under HTL conditions compared with ST.
      43.4% and 32.4% of carbon in WW11 and ST11 were released into the biocrude and
      aqueous phase in 500mL reactor, respectively. As much as 64.5% of the hydrogen
      was transferred to the aqueous phase. GC-MS results showed that the chemical
      compounds in the biocrude oil from WW consist of a variety of chemical
      constituents, such as hydrocarbons, acids, alcohols, ketones, phenols and
      aldehydes. These two biocrude oils contained 17.5% wt. and 8.64% wt.
      hydrocarbons, and 63.7% wt. and 79.8% wt. oxygen-containing compounds,
      respectively. TGA results showed that 69.3%-66.7% of the biocrude oil was
      gasified in 30 degrees C-400 degrees C. This study demonstrates the great
      potential for biocrude oil production from microalgae grown in biogas effluent
      via HTL.

PMID- 29660730
TI  - Enhancing anaerobic treatment of domestic wastewater: State of the art,
      innovative technologies and future perspectives.
AB  - Recent concerns over public health, environmental protection, and resource
      recovery have induced to look at domestic wastewater more as a resource than as a
      waste. Anaerobic treatment, owing to attractive advantages of energy saving,
      biogas recovery and lower sludge production, has been suggested as an alternative
      technology to the traditional practice of aerobic wastewater treatment, which is
      energy intensive, produces high excess of sludge, and fails to recover the
      potential resources available in wastewater. Sewage treatment by high-rate
      anaerobic processes has been widely reported over the last decades as an
      attractive method for providing a good quality effluent. Among the available high
      rate anaerobic technologies, membrane bioreactors feature many advantages over
      aerobic treatment and conventional anaerobic systems, since high treatment
      efficiency, high quality effluent, pathogens retention and recycling of
      nutrients, were generally achieved. The objective of this paper is to review the
      currently available knowledge on anaerobic domestic wastewater treatment for the
      mostly applied high-rate systems and membrane bioreactors, presenting benefits
      and drawbacks, and focusing on the most promising emerging technologies, which
      need more investigation for their scale-up.

PMID- 29660732
TI  - Safe and unsafe spaces: Non-fatal overdose, arrest, and receptive syringe sharing
      among people who inject drugs in public and semi-public spaces in Baltimore City.
AB  - The spaces in which drug use occurs constitutes a key aspect of the "risk
      environment" of people who inject drugs (PWID). We aimed to add nuance to the
      characterization of "safe" and "unsafe" spaces in PWID's environments to further
      understand how these spaces amplify the risk of morbidities associated with
      injection drug use. PWID were recruited through the Baltimore City syringe
      service program and through peer referral. Participants completed a socio
      behavioral survey. Multivariable logistic regression was used to identify
      associations between utilization of public, semi-public and private spaces with
      arrest, non-fatal overdose, and receptive syringe sharing. The sample of PWID (N
      = 283) was mostly 45 years and older (54%), male (69%), Black (55%), and heroin
      users (96%). Compared to PWID who primarily used private settings, the adjusted
      odds of recent overdose were greater among PWID who mostly used semi-public and
      public locations to inject drugs. We also found independent associations between
      arrest and semi-public spaces, and between receptive syringe sharing and public
      spaces (all p < 0.05). This study highlights the need for safe spaces where PWID
      can reduce their risk of overdose, likelihood of arrest and blood-borne diseases,
      and the dual potential of the environment in promoting health and risk.

PMID- 29660731
TI  - Remediation of multiple heavy metal-contaminated soil through the combination of
      soil washing and in situ immobilization.
AB  - The remediation of heavy metal-contaminated soils is a great challenge for global
      environmental sciences and engineering. To control the ecological risks of heavy
      metal-contaminated soil more effectively, the present study focused on the
      combination of soil washing (with FeCl3) and in situ immobilization (with lime,
      biochar, and black carbon). The results showed that the removal rate of Cd, Pb,
      Zn, and Cu was 62.9%, 52.1%, 30.0%, and 16.7%, respectively, when washed with
      FeCl3. After the combined remediation (immobilization with 1% (w/w) lime), the
      contaminated soils showed 36.5%, 73.6%, 70.9%, and 53.4% reductions in the
      bioavailability of Cd, Cu, Pb, and Zn (extracted with 0.11M acetic acid),
      respectively, than those of the soils washed with FeCl3 only. However, the
      immobilization with 1% (w/w) biochar or 1% (w/w) carbon black after washing
      exhibited low effects on stabilizing the metals. The differences in effects
      between the immobilization with lime, biochar, and carbon black indicated that
      the soil pH had a significant influence on the lability of heavy metals during
      the combined remediation process. The activity of the soil enzymes (urease,
      sucrase, and catalase) showed that the addition of all the materials, including
      lime, biochar, and carbon black, exhibited positive effects on microbial
      remediation after soil washing. Furthermore, lime was the most effective
      material, indicating that low soil pH and high acid-soluble metal concentrations
      might restrain the activity of soil enzymes. Soil pH and nutrition were the major
      considerations for microbial remediation during the combined remediation. These
      findings suggest that the combination of soil washing and in situ immobilization
      is an effective method to amend the soils contaminated with multiple heavy
      metals.

PMID- 29660733
TI  - An analysis of Belgian Cannabis Social Clubs' supply practices: A shapeshifting
      model?
AB  - BACKGROUND AND RESEARCH QUESTIONS: Cannabis Social Clubs (CSCs) are associations
      of cannabis users that collectively organize the cultivation and distribution of
      cannabis. As this middle ground supply model has been active in Belgium for over
      a decade, this paper aims to examine CSCs' supply practices, noting any shifts
      from previously reported features of the model. METHODS: We draw on interviews
      with directors of seven currently active Belgian CSCs (n = 21) and their cannabis
      growers (n = 23). This data was complemented by additional fieldwork, as well as
      a review of CSCs' key internal documents. RESULTS: Most Belgian CSCs are formally
      registered non-profit associations. One of the Belgian CSCs has developed a
      structure of sub-divisions and regional chapters. The Belgian CSCs supply
      cannabis to members only, and in some cases only medical users are admitted. CSCs
      rely on in-house growers, ensuring supply in a cooperative and closed-circuit
      way, despite changes to the distribution methods The associations are relatively
      small-scale and non-commercially driven. The introduction of formal quality
      control practices remains challenging. DISCUSSION: As the CSC model is often
      included in discussions about cannabis policy, but remains in most cases driven
      by self-regulatory efforts, it is important to take stock of how CSCs' supply
      function has been implemented in practice - as doing so will improve our
      understanding of the model and of the wider range of cannabis 'supply
      architectures'. This paper highlights the continuity and changes in CSC
      practices, noting the emergence of several different variants of the CSC model,
      which are classified in a first CSC typology.

PMID- 29660734
TI  - Interpretation of Serum Gonadotropin Levels in Hyperprolactinaemia.
AB  - BACKGROUND/AIMS: Hyperprolactinaemia is a common cause of amenorrhoea due to
      hypogonadotropic hypogonadism. Prolactin is hypothesised to impede the
      reproductive axis through an inhibitory action at the hypothalamus. However,
      limited data exist to aid the interpretation of serum gonadotropins in the
      context of hyperprolactinaemia. METHODS: Serum gonadotropin values were reviewed
      in 243 patients with elevated serum monomeric prolactin due to discrete
      aetiologies at a tertiary reproductive endocrine centre between 2012 and 2015.
      The cause of hyperprolactinaemia was categorised by an experienced
      endocrinologist/pituitary multidisciplinary team, unless superseded by histology.
      The most frequently encountered diagnoses were microprolactinoma (n = 88),
      macroprolactinoma (n = 46), non-functioning pituitary adenoma (NFPA) (n = 72),
      drug-induced hyperprolactinaemia (n = 22) and polycystic ovarian syndrome (PCOS)
      (n = 15). RESULTS: In patients with prolactinoma and modestly raised serum
      prolactin levels (< 4,000 mU/L), increasingly FSH-predominant gonadotropin values
      were observed with rising prolactin level, consistent with a progressive
      reduction in hypothalamic gonadotropin-releasing hormone (GnRH) pulsatility.
      Patients with prolactinoma and higher prolactin values (> 4,000 mU/L) were more
      likely to have a reduction in serum levels of both FSH and LH, consistent with
      direct pituitary gonadotrope dysfunction. Patients with macroadenoma and extremes
      of serum gonadotropin values (either serum FSH or LH > 8 IU/L) were more likely
      to have NFPA than prolactinoma. Patients with PCOS and hyperprolactinaemia had LH
      predominant secretion in keeping with increased GnRH pulsatility despite a raised
      prolactin level. CONCLUSION: The pattern of gonadotropin secretion in patients
      with hyperprolactinaemia reflects the underlying aetiology.

PMID- 29660735
TI  - The Anorexigenic Neural Pathways of Oxytocin and Their Clinical Implication.
AB  - Oxytocin was discovered in 1906 as a peptide that promotes delivery and milk
      ejection; however, its additional physiological functions were determined 100
      years later. Many recent articles have reported newly discovered effects of
      oxytocin on social communication, bonding, reward-related behavior, adipose
      tissue, and muscle and food intake regulation. Because oxytocin neurons project
      to various regions in the brain that contribute to both feeding reward (hedonic
      feeding) and the regulation of energy balance (homeostatic feeding), the
      mechanisms of oxytocin on food intake regulation are complicated and largely
      unknown. Oxytocin neurons in the paraventricular nucleus (PVN) receive neural
      projections from the arcuate nucleus (ARC), which is an important center for
      feeding regulation. On the other hand, these neurons in the PVN and supraoptic
      nucleus project to the ARC. PVN oxytocin neurons also project to the brain stem
      and the reward-related limbic system. In addition to this, oxytocin induces
      lipolysis and decreases fat mass. However, these effects in feeding and adipose
      tissue are known to be dependent on body weight (BW). Oxytocin treatment is more
      effective in food intake regulation and fat mass decline for individuals with
      leptin resistance and higher BW, but is known to be less effective in individuals
      with normal BW. In this review, we present in detail the recent findings on the
      physiological role of oxytocin in feeding regulation and the anorexigenic neural
      pathway of oxytocin neurons, as well as the advantage of oxytocin usage for anti
      obesity treatment.

PMID- 29660737
TI  - Treatment of a Paediatric Distal Femoral Malunion Deformity.
AB  - OBJECTIVE:  The aim of this article was to describe the surgical re-alignment
      technique and stabilization of a distal femoral deformity in a 6-week-old, male,
      Foxhound. METHODS:  A healing metaphyseal fracture, resulting in a valgus
      deformity with internal rotation, was observed just proximal to the distal
      femoral physis. The deformity was treated by an opening wedge osteotomy with
      lateral translation and external rotation of the distal epiphysis using a guide
      wire technique; a corticocancellous allograft bridged the defect, which was
      stabilized with a 2.0-mm locking Y-plate designed for human phalangeal fractures.
      RESULTS:  Successful deformity correction was obtained with subsequent healing of
      the osteotomy and maintained longitudinal bone growth. Sciatic neurapraxia
      developed as a result of a migrating adjunct pin (9 days post-operatively), which
      was removed. At long-term follow-up (4 years), a 12% shortening of the femur did
      result in addition to an asymptomatic grade 2 medial patellar luxation (MPL). The
      cause of the MPL was not evident; the owners declined treatment and the dog
      continued to function as an active hunting dog. CLINICAL SIGNIFICANCE:  Prior to
      ossification of the epiphyses in very young animals, which precludes effective
      radiographic pre-planning, the guide-wire technique can be utilized as the
      primary tool for performing angular deformity correction. Adequate fixation and
      stabilization can be obtained with small human specialty locking plates.

PMID- 29660738
TI  - Evaluating Stiffness of Fibreglass and Thermoplastic Splint Materials and Inter
      fragmentary Motion in a Canine Tibial Fracture Model.
AB  - OBJECTIVES:  Various materials are used to construct splints for mid-diaphyseal
      tibial fracture stabilization. The objective of this study was to compare
      construct stiffness and inter-fragmentary bone motion when fibreglass (FG) or
      thermoplastic (TP) splints are applied to either the lateral or cranial aspect of
      the tibia in a mid-diaphyseal fracture model. METHODS:  A coaptation bandage was
      applied to eight cadaveric canine pelvic limbs, with a custom-formed splint made
      of either FG or TP material applied to either the lateral or cranial aspect of
      the osteotomized tibia. Four-point bending tests were performed to evaluate
      construct stiffness and inter-fragmentary motion in both frontal and sagittal
      planes. RESULTS:  For a given material, FG or TP, construct stiffness was not
      affected by splint location. Construct stiffness was significantly greater with
      cranial FG splints than with cranial TP splints (p < 0.05), but this difference
      was not significant when comparing splints applied laterally (p = 0.15). Inter
      fragmentary motions in the sagittal and frontal planes were similar across splint
      types for cranial splints, but for lateral splints there was a 64% reduction in
      frontal plane motion when FG was used as the splint material (p = 0.03). CLINICAL
      SIGNIFICANCE:  FG produces a stiffer construct, but the difference is not
      reflected in a reduction in inter-fragmentary motion. For lateral splints, FG
      splints are associated with reduced inter-fragmentary motion as compared with TP
      and may therefore have slight superiority for this application.

PMID- 29660739
TI  - [Transthyretin Familial Amyloid Polyneuropathy - Disease Profile of a Multisystem
      Disorder].

PMID- 29660740
TI  - ?

PMID- 29660741
TI  - ?

PMID- 29660742
TI  - ?

PMID- 29660743
TI  - [Rehabilitation after Multiple Trauma].
AB  - Many polytrauma patients report significant long-term impairments to their
      physical and mental health, resulting in a reduction of their quality of life. In
      addition to the obvious physical accident sequences, psychological influences and
      the individual context factors pose special challenges to the rehabilitation team
      and the infrastructure of the facility. Professional reintegration and chronic
      pain are particularly common problems in the trauma rehabilitation. The central
      task of rehabilitation after accidents is the restoration or substantial
      improvement of the functional health and thus the reintegration into the social
      and professional environment. The overall rehabilitation goal is based on the
      biopsychosocial ICF model: the patient should achieve the best possible quality
      of life despite his functional impairments, and the workability and functional
      capability are to be restored as well as possible. This goal can only be reached
      after a lengthy process, in the course of which differentiated measures must be
      coordinated. This is the task of experienced doctors, therapists and
      rehabilitation managers, who accompany the patient permanently. The
      rehabilitation after serious accidents is to be distinguished from the "normal"
      orthopedic rehabilitation after elective interventions. The challenges of
      traumatic rehabilitation require special processes, infrastructures, as well as
      interrelated and coordinated rehabilitation phases. The three-phase model
      described in the "Weibetabuch Schwerverletztenversorgung der DGU" has to be
      differentiated. Between the discharge from the acute care clinic and the
      beginning of the post-acute rehabilitation, a "rehabilitation hole" frequently
      occurs. The early rehabilitation, by definition, a part of the acute treatment,
      cannot adequately close this hole. A 6-phase model is proposed. Phase C of post
      acute rehabilitation places particular demands on the rehabilitation facility.
      The further rehabilitation (phase E) provides specific measures, such as pain
      rehabilitation or activity-oriented procedures. A long-term follow-up of formerly
      seriously injured patients is necessary (phase F). An integration of trauma
      rehabilitation centers into the existing trauma network remains the long-term
      goal to improve the outcome after polytrauma.

PMID- 29660744
TI  - [Need of analgetics in children aged 2-12 years after tonsil surgery].
AB  - OBJECTIVE: Tonsil surgery is one of the most painful operations in childhood. The
      Children's and Infants' Postoperative Pain Scale (CHIPPS), the Faces Pain Scale
      Revised (FPS-R) and the little-known German version of the parents' postoperative
      pain measure (PPPM-D) are age-appropriate measures. Children undergoing
      intracapsular tonsillectomy (TO) or extracapsular tonsillectomy (TE) received the
      non-opioids ibuprofen (IBU) and paracetamol (PCM) on a "as needed"-basis
      requested by parents. A pain service checked pain scales and applied piritramide
      as rescue medication (RM) if required. Objective was evalution of sufficient
      analgesia. Endpoints were number of patients (PAT) needing the RM, doses of
      requested non-opioids, consistency of indications in different pain scales and
      correlation between pain and efficacy of the premedication or duration of the
      intervention. MATERIAL/METHODS: 3 measures were carried out daily: CHIPPS for PAT
      <= 4 years old, FPS-R from the age of 5. Parents completed the PPPM-D. Exceeding
      a cut-off score of 4 in CHIPPS or FPS-R or 6 in PPPM-D was rated as indication
      for RM. RESULTS: We included 68 PAT in an interim analysis. Mean daily doses of
      non-opioids within the first 3 postoperative days were as follows: PAT undergoing
      TE got 14,1-16,3 mg/Kg IBU and 4,2-12,4 mg/Kg PCM. PAT undergoing TO got 10,8
      14,7 mg/Kg IBU and 5,2-8,8 mg/Kg PCM. On 212 visits PAT required RM, but 121
      times it was detected in the PPPM-D only. After exclusion of potentially false
      positive results remained 67 % PAT after TE and 48 % PAT after TO with at least 1
      indication for RM. The study was terminated due to the high need for RM.
      CONCLUSIONS: The need of non-opioids was underrated. Combining the PPPM-D with
      established measures may improve the postoperative pain therapy.

PMID- 29660745
TI  - Omental Vascularized Lymph Node Flap: A Radiographic Analysis.
AB  - BACKGROUND:  Vascularized lymph node transfer is an increasingly popular option
      for the treatment of lymphedema. The omental donor site is advantageous for its
      copious soft tissue, well-defined collateral circulation, and large number of
      available nodes, without the risk of iatrogenic lymphedema. The purpose of this
      study is to define the anatomy of the omental flap in the context of vascularized
      lymph node harvest. METHODS:  Consecutive abdominal computed tomography
      angiography (CTA) images performed at a single institution over a 1-year period
      were reviewed. Right gastroepiploic artery (RGEA) length, artery caliber, lymph
      node size, and lymph node location in relation to the artery were recorded. A two
      tailed Z-test was used to compare means. A Gaussian Mixture Model confirmed by
      normalized entropy criterion was used to calculate three-dimensional lymph node
      cluster locations along the RGEA. RESULTS:  In total, 156 CTA images met
      inclusion criteria. The RGEA caliber at its origin was significantly larger in
      males compared with females (p < 0.001). An average of 3.1 (1.7) lymph nodes were
      present per patient. There was no significant gender difference in the number of
      lymph nodes identified. Average lymph node size was significantly larger in males
      (4.9 [1.9] * 3.3 [0.6] mm in males vs. 4.5 [1.5] * 3.1 [0.5] mm in females; p <
      0.001). Three distinct anatomical variations of the RGEA course were noted, each
      with a distinct lymph node clustering pattern. Total lymph node number and size
      did not differ among anatomical subgroups. CONCLUSION:  The omentum is a reliable
      lymph node donor site with consistent anatomy. This study serves as an aid in
      preoperative planning for vascularized lymph node transfer using the omental
      flap.

PMID- 29660746
TI  - Free versus Pedicled Perforator Flaps for Lower Extremity Reconstruction: A
      Multicenter Comparison of Institutional Practices and Outcomes.
AB  - BACKGROUND:  Of all body regions, lower extremity wounds have been and remain the
      greatest challenge. Perforator free flaps have been accepted as a reasonable
      option to solve this dilemma but require the complexity of microsurgery. As a
      consequence, the possibility that pedicled perforator flaps could supplant even
      perforator free flaps has recently gained intense enthusiasm. METHODS:  A
      retrospective investigation was undertaken to compare the validity for the use of
      perforator flaps of all types at three dissimilar institutions, that is, a
      university, a regional center, and a community hospital. All flaps performed in
      the 5-year period, 2011 to 2015, were included to allow at least 1-year follow-up
      before data analysis. A total of 433 free perforator flaps and 52 pedicled
      perforator flaps had been performed specifically for the lower extremity.
      RESULTS:  Patient demographics, wound etiology, and comorbidities were similar
      for all institutions. Free flaps were more commonly needed after trauma and for
      chronic ulcers. Pedicled flaps were more likely an option after tumor excision.
      Large defects or those involving the foot were better served by free flaps.
      Overall success for free perforator flaps was 90.1% and for pedicled perforator
      flaps was 92.3%, with no significant difference noted (p = 0.606) between
      institutions. Peripheral vascular disease was the only significant comorbidity
      risk factor for both free and pedicled flap failure. CONCLUSION:  Perforator
      flaps in general have become a reasonable solution for soft tissue defects of the
      lower extremity. Following careful consideration of the etiology, dimensions,
      location, patient comorbidities, and presence of adequate perforators, a pedicled
      or free perforator flap could potentially be successful. Pedicled perforator
      flaps, if adequate healthy soft tissues remain adjacent to the defect, forecast a
      continuance of the evolution in seeking simplicity yet reliability by the best
      flap possible for soft tissue closure of the lower limb wound.

PMID- 29660747
TI  - Paraspinal Muscles of Patients with Lumbar Diseases.
AB  - OBJECTIVE:  The treatment of atrophy or increased fat infiltration of the lumbar
      paraspinal muscles of patients with back pain, lumbar radiculopathy, or lumbar
      degenerative kyphosis is controversial. We review the literature on changes in
      the lumbar paraspinal muscles of these patients. METHODS:  We searched Medline
      for relevant English-language articles and retrieved 25 articles published from
      1993 to 2017 on changes in the lumbar paraspinal muscles; 21 met our study
      criteria. We categorized each article into three groups: randomized clinical
      trial, nonrandomized prospective study, or retrospective study. RESULTS:  We
      found 1 randomized prospective, 3 nonrandomized prospective, and 17 retrospective
      studies. Atrophies of the multifidus muscle are found at the level of the L5
      vertebral body in patients with back pain, lumbar radiculopathy, and lumbar
      degenerative kyphosis. Increased fat infiltration to the multifidus muscle was
      found in the patients with lumbar radiculopathy or lumbar degenerative kyphosis.
      However, there are controversies over fat infiltration to the multifidus muscle
      in the patients with back pain and the efficiency of a paramedian surgical
      approach to prevent the atrophy of the multifidus muscle. CONCLUSIONS:  Atrophy
      of the multifidus muscle was found in patients with back pain, lumbar
      radiculopathy, and lumbar degenerative kyphosis. There was increased fat
      infiltration to the multifidus muscle in those patients with lumbar radiculopathy
      or lumbar degenerative kyphosis.

PMID- 29660748
TI  - Monodisperse Rattle-Structured Gold Nanorod-Mesoporous Silica Nanoparticles Core
      Shell as Sulforaphane Carrier and its Sustained-Release Property.
AB  - Sulforaphane (SF) was loaded into the multi-functioned rattle-structured gold
      nanorod mesoporous silica nanoparticles core-shell to improve its stability and
      efficacy through its efficient delivery to tumors. The rattle-structured gold
      nanorod mesoporous silica nanoparticles (rattle-structured AuNR@mSiO2 core-shell
      NPs) were obtained by covering the surface of Au NPs with Ag and mSiO2 shell and
      subsequently selective Ag shell etching strategy. Then the surface of rattle
      structured AuNR@mSiO2 NPs was decorated with thiolated polyethylene glycol-FITC
      and thiolated polyethylene glycol-folic acid to the designed form. The obtained
      FITC/FA@ [rattle-structured AuNR@mSiO2] NPs was characterized by different
      techniques including energy dispersive X-ray spectroscopy (EDX), scanning and
      transmission electron microscopy (SEM & TEM), UV-visible spectrophotometer and
      dynamic light scattering (DLS). The FITC/FA@ [rattle-structured AuNR@mSiO2] NPs
      has an average diameter around ~33 nm, which increases to ~38 nm after the
      loading of sulforaphane. The amount of the loaded drug was ~ 2.8*10-4 mol of SF
      per gram of FITC/FA@ [rattle-structured AuNR@mSiO2] NPs. The rattle-structured
      AuNR@mSiO2 and FITC/FA@ [rattle-structured AuNR@mSiO2] NPs showed little inherent
      cytotoxicity, whereas the SF loaded FITC/FA@ [rattle-structured AuNR@mSiO2] NPs
      was highly cytotoxic in the case of MCF-7 cell line. Finally, Fluorescence
      microscopy and flow cytometry were used to demonstrate that the nanoparticles
      could be accumulated in specific regions and SF loaded FITC/FA@ [Fe3O4@Au] NPs
      efficiently induce apoptosis in MCF-7 cell line Graphical Abstract.

PMID- 29660749
TI  - Antimicrobial Peptidomimetics for Recurrent Septicemia Infections: In Vitro Study
      for Immuno Compromised Disease Target.
AB  - The frequency of Bacillus subtilis infection such as pneumonia pan-opthalmitis,
      visceral abscess or musculoskeletal infection etc. complications following
      bacteremia, meningitis in children & the infection associated with majority of
      motor vehicle accidents associated with trauma & gun shoot injury. Antibiotics
      which appear especially useful in the treatment of Bacillus. infection are
      clindamycin and vancomycin to which vast majority of strains are susceptible in
      vitro. Our objective is to test the synthesized peptidomimetics with the efforts
      mainly directed towards the identification of antibacterial compounds against
      recurrent septicemia infection. Six peptidomimetics namely G-A-L-D (C60-soot Glu
      ala-leu-Asp), D-P-F (C60-soot Asp-pro-Phe), I-R (C60-soot Ile-Arg), L-R (C60-soot
      leu-Arg), E-R (C60-soot Glu-Arg), D-E (C60-soot Asp-Glu), the column eluted
      compounds were tested for disc diffusion using gram positive Bacillus Subtilis
      strains at different concentrations predicted by pH and inhibitory
      concentrations. I-R (C60-soot Ile-Arg), & D-E (C60-soot Asp-Glu) was found to be
      very effective along with 5 compounds against Bacillus Subtilis strain tested.
      Maximum activity 100 ug/ml for synthesized peptidomimetics with the corresponding
      zonal inhibition diameter (11 mm; 11 mm; 14 mm; 11 mm; 11 mm; 14 mm) against
      Bacillus subtilis strain. This is the first evidence based report that proves I-R
      (C60-soot Ile-Arg) & D-E (C60-soot Asp-Glu) has shown antibacterial action
      against gram positive strains of Bacillus Subtilis against recurrent septicemia
      infection.

PMID- 29660750
TI  - [German Version of the Sibling Relationship Questionnaire (SRQ-deu): Normative
      Data for Children and Adolescents].
AB  - The SRQ-deu assesses the quality of sibling relationships from either the
      perspective of the child (self-report version) or of the parent (parent-report
      version). Its validity has been demonstrated in a first examination 6. Normative
      data, however, are not yet available. Hence, the current study presents normative
      data for the SRQ-deu self-report version based on a sample of 961 German children
      and adolescents aged 8 to 18 years. The effects of age and sibling status
      (younger/older sibling) are taken into account. This publication of normative
      data for children and adolescents allows for the SRQ-deu (self-report) to be used
      in different contexts, both for clinical and research purposes.

PMID- 29660751
TI  - [Exposure Therapy with the Help of a Wearable Defibrillator Device used in the
      Treatment of Severe Obsessive-Compulsive Disorder and Congenital LQTS - An
      Example for Interdisciplinary Treatment].
AB  - We report on a case of a young female suffering from both obsessive-compulsive
      disorder (OCD) and a severe underlying cardiac disease. Due to the somatic
      comorbidity, treatment according to guidelines with exposure and reaction
      prevention was not initially conducted, due to potentially fatal risks to the
      patient. However, through collaboration with a cardiology clinic, we were able to
      find an innovative solution which allowed for the continuation of the exposure
      therapy. This case report demonstrates a successful interdisciplinary
      collaboration and is intended to sensitize the reader to the need for checking
      for somatic contraindications before conducting exposure therapy.

PMID- 29660752
TI  - Optimal Timing of Delivery in Women with Higher Order Cesareans: A Cohort Study.
AB  - OBJECTIVE:  To evaluate whether a planned early term delivery or a planned 39
      week delivery is associated with differences in perinatal outcomes in women
      undergoing a higher order cesarean (HOC). STUDY DESIGN:  This cohort study
      included women with singleton gestations with a history of three or more prior
      cesareans who delivered at one of two urban tertiary care hospitals. One center
      routinely delivered HOC at 39 weeks' gestation and the other at 37 weeks.
      Maternal and neonatal morbidities were compared using bivariable and
      multivariable analyses. RESULTS:  The policy of 37-week delivery was associated
      with a decrease in unscheduled deliveries (15.3 vs. 41.1%; p < 0.001). Planned
      delivery at 37 weeks was associated with a decreased incidence of composite
      maternal morbidity (1.6 vs. 7.9%; p = 0.002) and 5-minute Apgar score less than 7
      (0.4 vs. 6.4%; p < 0.001), but these differences were not significant after
      controlling for potential confounders (adjusted odds ratio [aOR]: 0.30, 95%
      confidence interval [CI]: 0.08-1.17; aOR: 0.13, 95% CI: 0.01-1.30, respectively).
      There were no other differences in perinatal outcomes. CONCLUSION:  Compared with
      planned delivery at 39 weeks, a policy of planned delivery at 37 weeks was
      associated with a reduction in unscheduled deliveries, but there were no measured
      differences in perinatal outcomes.

PMID- 29660754
TI  - Antidepressant Prescription and Risk of Lung Cancer: A Nationwide Case-Control
      Study.
AB  - INTRODUCTION: In recent decades, concern about safety of antidepressants has been
      raised but the risk between antidepressants and lung cancer has not yet been
      established. METHODS: A case-control study was conducted by using a nationwide
      database in Taiwan. The case groups were new onset lung cancer diagnosis during
      1999-2008 and age- and gender-matched controls were selected among those without
      any cancer. The cumulative exposure dose before the lung cancer diagnosis was
      added and risks were calculated according to the levels of defined daily dose and
      classes of antidepressants. RESULTS: A total of 39,001 individuals with lung
      cancer and 189,906 individuals without lung cancer between 1999 and 2008 were
      included in the analysis. Antidepressants, of any class, were not associated with
      elevated risks for lung cancer with the exception of bupropion at high exposure
      levels (odds ratio=4.81, 95% confidence interval=1.39-16.71). DISCUSSION:
      Antidepressant prescription was not associated with elevation of lung cancer
      incidence using a nationally representative sample. The elevated risk for lung
      cancer with bupropion at high doses may be a bias by indication and warrant
      longitudinal investigation.

PMID- 29660753
TI  - Crataegus Special Extract WS 1442 Effects on eNOS and microRNA 155.
AB  - Increased expression of microRNA 155 (miR-155) results in a decrease in
      endothelial nitric oxide synthase (eNOS) expression and impaired endothelial
      function. Factors that have been shown to increase expression of miR-155 may be
      mitigated by WS 1442, an extract of hawthorn leaves and flowers (Crataegus
      special extract) that contains a range of pharmacologically active substances
      including oligomeric proanthocyanidins and flavonoids. The purpose of this study
      is to determine the effect of WS 1442 on the expression of miR-155 and eNOS in
      the presence of tumor necrosis factor (TNF-alpha). Human umbilical vein
      endothelial cells (HUVECs) were studied after the exposure to TNF-alpha, with or
      without simvastatin (positive control) and WS 1442. The expression levels of
      eNOS, phosphorylated eNOS, and miR-155 in the different HUVEC treatment groups
      were determined by western blot and quantitative real-time polymerase chain
      reaction, respectively. To evaluate the effect of WS 1442 on the eNOS activity,
      the medium and intracellular nitrate/nitrite (NO) concentrations were also
      analyzed using a colorimetric Griess assay kit. The results demonstrated that TNF
      alpha upregulated miR-155 expression and decreased eNOS expression and NO
      concentrations. WS 1442 also increased miR-155 expression and decreased eNOS
      expression but, unlike TNF-alpha, increased phosphorylated eNOS expression and NO
      concentrations. Surprisingly, WS 1442 increased miR-155 expression; however, WS
      1442 mitigated the overall negative effect of miR-155 on decreasing eNOS
      expression by increasing expression of phosphorylated eNOS and resulting in an
      increase in NO concentrations. In the setting where miR-155 may be expressed, WS
      1442 may offer vascular protection by increasing the expression of phosphorylated
      eNOS.

PMID- 29660755
TI  - [Beckwith-Wiedemann Syndrome (BWS) Current Status of Diagnosis and Clinical
      Management: Summary of the First International Consensus Statement].
AB  - Beckwith-Wiedemann syndrome (BWS) belongs to the group of imprinting disorders
      and is characterized by variable clinical features, including overgrowth,
      macroglossia, abdominal wall defect, neonatal hypoglycemia, body asymmetry and an
      increased risk for embryonal tumors. In the majority of cases, molecular
      alterations of the Imprinting Center (IC) regions in the chromosomal region
      11p15.5 can be detected, and a correlation of single clinical features with
      specific genomic and epigenetic changes is obvious. Therefore, the detailed
      molecular diagnosis is a prerequisite for a precise prediction of the tumor risk
      and the tumor spectrum. Furthermore, it is the basis for a well-directed genetic
      counselling of the families. Despite a huge number of comprehensive studies based
      on a large number of cases, standardized diagnostic criteria and advices for
      therapeutic management were missing. In the following, the recently published
      first international consensus guidelines drafted by 41 experts in the field of
      BWS from 11 European countries and the USA are summarized. Patients support
      groups had been included as well. In total, 72 consented recommendations for
      clinical and molecular diagnosis as well as for the clinical management of BWS
      have been published. They refer both to patients with the classical BWS phenotype
      and to those with "atypical" phenotypes which are summarized as BWS spectrum
      (BWSp). A modified clinical scoring system is now suggested, which represents the
      basis to initiate molecular diagnostics. Therapeutic recommendations comprise the
      major clinical questions in BWS/BWSp, i. e. early monitoring of an increased
      tumor risk, treatment of the macroglossia and the abdominal wall defects, and
      therapeutic interventions for hypoglycemia. However, though there was a broad
      consensus on the majority of therapeutic interventions, discussions on tumor
      monitoring are foreseeable. Thus, prospective studies to evaluate the consensus
      guidelines and their use are planned.

PMID- 29660756
TI  - Use of Palivizumab in Germany - Report from the German SynagisTM Registry 2009 -
      2016.
AB  - BACKGROUND: Following national recommendations, palivizumab is administered in
      Germany to high-risk infants to prevent hospitalizations related to Respiratory
      Syncytial Virus infection. METHODS: In this post marketing observational study
      (German SYNAGISTM Registry) data on risk factors and the clinical course of
      children, who received at least one palivizumab injection between 2009-2016 (01
      September to June 30) were entered into an internet-based data entry system by
      the attending physicians after informed consent. RESULTS: 63 572 immunizations
      were documented for 12 729 evaluable patients (EVP) from 2009 to 2016, with an
      average of 5.0 immunizations per patient per season. 45% of infants received more
      than 5 injections. The predominant primary reason for immunization was premature
      birth (74%). In the EVP the rate of hospitalizations with causal relationship to
      RSV was 0.7% (=92/12 729) or 1.2% in a worst case scenario including patients
      with missing RSV test. In patients with hemodynamically significant congenital
      heart disease as main indication, RSV-related hospitalization rate was 0.8%.
      Intensive care was necessary in 16.9% (median duration 3 days), mechanical
      ventilation in 8.0%. No death related to RSV infection was reported. CONCLUSION:
      Keeping in mind the limitations of an uncontrolled prospective observational
      study, our results confirm the effectiveness and safety of palivizumab
      prophylaxis. The total number of patients with hsCHD is lower than expected. A
      better adjustment to the regional epidemiology would probably reduce the need for
      more than 5 injections.

PMID- 29660757
TI  - Spectrum of Parvovirus B19 Infection Presentations in Children with Underlying
      Hemato-oncologic Disorders: A Case Series.

PMID- 29660758
TI  - Intracellular Expression of Antifreeze Peptides in Food Grade Lactococcus lactis
      and Evaluation of Their Cryoprotective Activity.
AB  - : Antifreeze peptides can protect living organisms from low temperatures by
      preventing damage or killing due to ice crystal formation between cells.
      Therefore, antifreeze peptides can be used as a low temperature protectant for
      cryopreservation of cells and tissues, and also in food production. In this
      study, a recombinant SF-P gene was constructed and inserted into pNZ8149 to
      construct a food grade expression vector, which was then electroporated into
      Lactococcus lactis NZ3900. The expression of the target protein was induced using
      Nisin, and the optimal expression condition was determined to be a pH of 6.0,
      Nisin concentration of 25 ng/mL, temperature of 37  degrees C, and incubation
      time of 6 hr. Compared to the strain NZ3900 and the recombinant strain SF-P1
      without addition of Nisin, the recombinant strain SF-P2 showed the highest cell
      survival and thermal hysteresis activity, and had a reduction in the changes of
      activities of extracellular and intracellular lactate dehydrogenase and beta
      galactosidase after freezing. Moreover, analysis by SEM showed that SF-P2 cells
      were more completely and regularly shaped than other strains, displayed no
      obvious leakage of cell contents, and had an intact boundary between cells after
      freezing. These results indicate that the recombinant strain SF-P2 has a
      protective effect against freezing. This paper presents a food grade expression
      system for an antifreeze peptide SF-P using L. lactis as a host, and shows that
      the intracellular expression of antifreeze peptide could protect the cellular
      integrity and physiological functions of L. lactis. PRACTICAL APPLICATION: The
      recombinant Lactococcus lactis with intracellular expression of antifreeze
      peptides SF-P could reduce the damage of bacteria cells induced by freezing or
      freeze drying, so, it could be applied in the process of freezing food without
      separation, such as the manufacture of yoghurt ice cream, frozen dough, and so
      on.

PMID- 29660760
TI  - Racial disparities in postmastectomy breast reconstruction: National trends in
      utilization from 2005 to 2014.
AB  - BACKGROUND: Evidence of racial disparities in the receipt of postmastectomy
      breast reconstruction is well documented. The objective of this study was to
      describe trends in racial disparities overall and by reconstructive technique.
      METHODS: The American College of Surgeons National Surgical Quality Improvement
      Program database was used to identify women who underwent mastectomy and/or
      breast reconstruction from 2005 to 2014. Patient demographics were recorded, and
      cases were grouped by reconstructive status and technique. Trends were assessed
      with the Cochran-Armitage test and the index of disparity. RESULTS: Over the
      study period, 92,960 postmastectomy patients were identified (77,049 white women,
      10,396 black women, 4939 Asian women, and 576 Native American women), of whom
      46,931 underwent reconstruction. Of these, 7692 women underwent autologous
      reconstructions (3913 free flaps and 3696 pedicled flaps). From 2005 to 2014,
      receipt of breast reconstruction by postmastectomy patients rose from 33.2% to
      60.0%, receipt of autologous reconstruction by patients who underwent breast
      reconstruction fell from 30.4% to 15.9%, and receipt of free-flap reconstruction
      by patients who underwent autologous reconstruction rose from 15.0% to 70.8%.
      These trends were significant in all racial subgroups (P < .001), except for
      Native Americans (P = .269). The index of disparity decreased from 51.4% to 22.6%
      for overall receipt of breast reconstruction, decreased from 10.7% to 7.0% for
      tissue expander and implant-based reconstruction, increased from 18.0% to 27.3%
      for autologous reconstruction, and decreased from 66.7% to 4.3% for free-flap
      reconstruction. CONCLUSIONS: The use of postmastectomy breast reconstruction is
      steadily rising in the United States. Racial disparities persist, but progress
      has been made. Further efforts are needed to reduce racial disparities. Cancer
      2018;124:2774-2784. (c) 2018 American Cancer Society.

PMID- 29660759
TI  - PARP inhibitors in breast cancer: Bringing synthetic lethality to the bedside.
AB  - Individuals with breast and ovarian cancer susceptibility gene 1 (BRCA1) or BRCA2
      germline mutations have a significantly increased lifetime risk for breast and
      ovarian cancers. BRCA-mutant cancer cells have abnormal homologous recombination
      (HR) repair of DNA. In these tumors, the base excision repair (BER) pathway is
      important for cell survival. The poly(adenosine diphosphate-ribose) polymerase
      (PARP) enzymes play a key role in BER, and PARP inhibitors are effective in
      causing cell death in BRCA-mutant cells while sparing normal cells-a concept
      called synthetic lethality. PARP inhibitors are the first cancer therapeutics
      designed to exploit synthetic lethality. Recent clinical trials in BRCA-mutant,
      metastatic breast cancer demonstrated improved outcomes with single-agent PARP
      inhibitors (olaparib and talazoparib) over chemotherapy. However, resistance to
      PARP inhibitors remains a challenge. Primarily due to myelosuppression, the
      combination of PARP inhibitors with chemotherapy has been difficult. Novel
      combinations with chemotherapy, immunotherapy, and other targeted therapies are
      being pursued. In this review, the authors discuss current knowledge of PARP
      inhibitors in BRCA-mutant breast cancer and potential future directions for these
      agents. Cancer 2018;124:2498-506. (c) 2018 American Cancer Society.

PMID- 29660761
TI  - Interactions of Dihydromyricetin, a Flavonoid from Vine Tea (Ampelopsis
      grossedentata) with Gut Microbiota.
AB  - : Dihydromyricetin (DMY) is the main bioactive constituent in vine tea
      (Ampelopsis grossedentata), which was predominantly distributed in the
      gastrointestinal tract and showed poor oral bioavailability. Our aim was to
      systematically investigate the interactions of DMY with gut microbiota. Through
      the metabolism study of DMY by fecal microflora in vitro, it was found that DMY
      could be metabolized into three metabolites by fecal microflora via reduction and
      dehydroxylation pathways, and the dehydroxylation metabolite was the dominant
      one. Meanwhile, in order to consider the influence of gut microbiota metabolism
      on the pharmacokinetics of DMY, the pharmacokinetics of DMY in control and pseudo
      germ-free rats were compared. It was shown that area under the curve (AUC) could
      only slightly increase, however, peak concentration (Cmax ) could significantly
      increase in the pseudo-germ-free rats compared with the control rats, which
      indicated the gut microbiota metabolism played an important role in the
      pharmacokinetics of DMY. In addition, the long-term influence of DMY on gut
      microbiota composition by using 16S rRNA pyrosequencing was further investigated.
      And it was found that DMY could markedly alter the richness and diversity of the
      gut microbiota and modulate the gut microbiota composition. The present findings
      will be helpful for the future development and clinical application of DMY.
      PRACTICAL APPLICATION: The gut microbiota plays an important role in the
      pharmacokinetics of flavonoids. As well, the long-term supplements of flavonoids
      could alter the gut microbiota composition in turn. The study aims to clarify the
      mutual interaction of DMY with gut microbiota, which may lead to new information
      with respect to the mechanism study and clinical application of DMY.

PMID- 29660762
TI  - A facile PCR-RFLP method for genotyping of ITPA rs1127354 and rs7270101
      polymorphisms.
AB  - BACKGROUND: Inosine triphosphate pyrophosphatase (ITPA) gene single nucleotide
      polymorphisms (SNPs), rs1127354 and rs7270101, may cause a functional impairment
      in ITPase enzyme, resulting anemia protection in patients with chronic hepatitis
      C virus (HCV) infection undergoing ribavirin (RBV)-dependent regimens. The main
      purpose of this study was to provide and validate a simple, rapid, and
      inexpensive polymerase chain reaction-restriction fragment length polymorphism
      (PCR-RFLP) technique for genotyping of ITPA rs1127354 and rs7270101 polymorphisms
      in chronic HCV-infected patients. METHODS: In the current study, 100 Iranian
      patients with chronic hepatitis C were examined and genotyped for ITPA rs1127354
      and rs7270101 gene polymorphisms. To genotype rs1127354 and rs7270101
      polymorphisms, PCR-RFLP technique and sequencing technique were performed on
      these samples. To validate the PCR-RFLP method, the PCR-RFLP genotyping results
      should be 100% concordant with the PCR-sequencing results. RESULTS: The rs1127354
      and rs7270101 polymorphisms of ITPA gene were genotyped by PCR-RFLP technique and
      sequencing simultaneously, and the results of both techniques were 100%
      concordant in all 100 patients. Both PCR-RFLP and sequencing techniques indicated
      that the genotypic frequency of rs7270101 was 80% AA, 19% AC and 1% CC, and for
      rs1127354 was 79% CC, 20% CA and 1% AA, respectively. CONCLUSION: We developed
      and validated a rapid and inexpensive PCR-RFLP technique for the detection of
      ITPA rs1127354 and rs7270101 gene polymorphisms.

PMID- 29660763
TI  - Diversity, Function, and Application of Clostridium in Chinese Strong Flavor
      Baijiu Ecosystem: A Review.
AB  - : Baijiu is a Chinese traditional distilled liquor with an annual yield over
      13.12 million tons. Strong flavor baijiu (SFB) also called Luzhou-flavor liquor,
      takes account for > 70% of the total baijiu produced. SFB is produced by an open
      solid fermentation process with a complex microbial ecosystem. Clostridium is one
      of the most important microorganisms for the formation of the main flavor
      compounds of SFB, such as ethyl caproate. In this paper, we review current
      research progress on the Clostridium in the SFB ecosystem, focusing on the
      species diversity, physiological and metabolic features along with interspecies
      interactions. Systems biology approaches for the study of Clostridium from SFB
      ecosystems were discussed and explored. Furthermore, current applications of
      Clostridium in SFB production were discussed. PRACTICAL APPLICATION: Strong
      flavor baijiu (SFB) accounts for more than 70% of total yield of Chinese baijiu,
      which exists for hundreds of years. Clostridium is common in SFB ecosystem and
      identified to be one of main contributors of flavor compounds in SFB. Study on
      the Clostridium from SFB ecosystem is not only helpful for the understanding of
      flavor compounds formation mechanism, but also the improvement of SFB quality.
      This study focuses on the current researches on the Clostridium species in SFB
      ecosystem, including the species diversity, physiological and metabolic features,
      and applications.

PMID- 29660764
TI  - Prognostic utility of MELD-XI in adult congenital heart disease patients
      undergoing cardiac transplantation.
AB  - BACKGROUND: Model of End-Stage Liver Disease eXcluding INR (MELD-XI) at cardiac
      transplant has demonstrated prognostic survival utility, but has not been
      specifically validated in adult congenital heart disease (ACHD) in a registry
      study. METHODS: Adults undergoing first-time orthotopic heart transplant from
      2005 to 2015 in the United Network for Organ Sharing (UNOS) registry were
      examined in parallel: ACHD (n = 543), ischemic-dilated cardiomyopathy (IDCM, n =
      6954) and valvular heart disease (VHD, n = 355). Our primary endpoint was a
      composite of death, graft failure, and retransplantation assessed at 3 months
      (early), and those with freedom from early endpoint were reassessed at 5 years
      (late). Interactions between hepatorenal indices and waitlist time were examined.
      Secondary outcomes relating to long-term morbidity were assessed at late
      endpoint. Freedom from endpoint analysis in ACHD at clinically relevant endpoints
      was also conducted. RESULTS: Model of End-Stage Liver Disease eXcluding INR score
      at transplant associated with an increased risk of early endpoint in all cohorts.
      At late endpoint, bilirubin level associated with increased risk uniquely in
      ACHD. CONCLUSIONS: Model of End-Stage Liver Disease eXcluding INR holds
      prognostic application to ACHD in early time points and demonstrates unique
      waitlist interactions. Transplant bilirubin level may hold significance in long
      term risk stratification of the ACHD population. Time on waitlist is an important
      consideration to contextualize these values.

PMID- 29660765
TI  - Real-Time Observation of Order-Disorder Transformation of Organic Cations Induced
      Phase Transition and Anomalous Photoluminescence in Hybrid Perovskites.
AB  - A fundamental understanding of the interplay between the microscopic structure
      and macroscopic optoelectronic properties of organic-inorganic hybrid perovskite
      materials is essential to design new materials and improve device performance.
      However, how exactly the organic cations affect the structural phase transition
      and optoelectronic properties of the materials is not well understood. Here, real
      time, in situ temperature-dependent neutron/X-ray diffraction and
      photoluminescence (PL) measurements reveal a transformation of the organic cation
      CH3 NH3+ from order to disorder with increasing temperature in CH3 NH3 PbBr3
      perovskites. The molecular-level order-to-disorder transformation of CH3 NH3+ not
      only leads to an anomalous increase in PL intensity, but also results in a
      multidomain to single-domain structural transition. This discovery establishes
      the important role that organic cation ordering has in dictating structural order
      and anomalous optoelectronic phenomenon in hybrid perovskites.

PMID- 29660766
TI  - Disparities in out-of-pocket inpatient expenditures in rural Shaanxi Province,
      western China from 2011 to 2014: a time series analysis.
AB  - OBJECTIVE: To investigate the long-term trend of disparity of monthly average out
      of-pocket inpatient expenditures (OOP) between areas with different developing
      levels since the new healthcare reform. METHODS: Time series regression was used
      to assess the trend of disparities of OOP and monthly average inpatient
      expenditures (AIE) between areas with different developing levels in rural
      Shaanxi Province, western China. The data of OOP and AIE in primary health
      institutions, secondary hospitals, tertiary hospitals and also all levels of the
      hospital were analysed separately covering the period 2011 through to 2014.
      RESULTS: The disparity of AIE at all levels of hospitals was increasing
      (coefficient = 0.003, P = 0.029), and only the disparity of AIE in secondary
      hospitals was statistical significant (coefficient = 0.003, P = 0.012) when
      separately considering different levels of the hospital. The disparity of OOP in
      all levels of the hospital was increasing (coefficient = 0.007, P = 0.001), and
      the OOP in primary hospitals contributed most of the disparity (coefficient =
      0.019, P = 0.000), followed by OOP in secondary (coefficient = 0.008, P = 0.003)
      and tertiary hospitals (coefficient = 0.004, P = 0.091). CONCLUSIONS: A
      statistically significant absolute increase in the trend of disparities of OOP
      and AIE at all levels of hospital was detected after the new healthcare reform in
      Shaanxi Province, western China. The increase rate of disparity of OOP was bigger
      than that of AIE. A modified health insurance plan should be proposed to
      guarantee equity in the future.

PMID- 29660767
TI  - Organocatalytic Atroposelective Intramolecular [4+2] Cycloaddition: Synthesis of
      Axially Chiral Heterobiaryls.
AB  - The enantioselective construction of axially chiral aryl-naphthopyran skeletons
      was realized by organocatalytic atroposelective intramolecular [4+2]
      cycloaddition of in situ generated vinylidene ortho-quinone methides, from 2
      ethynylphenol derivatives, with alkynes. Through this method, the
      heteroatropisomers were obtained with excellent yields and enantioselectivities.
      Moreover, a speculative model of the stereochemical outcome is proposed based on
      preliminary mechanistic studies. The products having various functional groups
      can be easily transformed into valuable intermediates as either potential ligands
      or organocatalysts.

PMID- 29660768
TI  - CuH-Catalyzed Asymmetric Hydroamidation of Vinylarenes.
AB  - A CuH-catalyzed enantioselective hydroamidation reaction of vinylarenes has been
      developed using readily accessible 1,4,2-dioxazol-5-ones as electrophilic
      amidating reagents. This method provides a straightforward and efficient approach
      to synthesize chiral amides in good yields with high levels of enantiopurity
      under mild conditions. Moreover, this transformation tolerates substrates bearing
      a broad range of functional groups.

PMID- 29660769
TI  - Influenza-associated mortality determined from all-cause mortality, Denmark
      2010/11-2016/17: The FluMOMO model.
AB  - BACKGROUND: In temperate zones, all-cause mortality exhibits a marked
      seasonality, and influenza represents a major cause of winter excess mortality.
      We present a statistical model, FluMOMO, which estimate influenza-associated
      mortality from all-cause mortality data and apply it to Danish data from 2010/11
      to 2016/17. METHODS: We applied a multivariable time series model with all-cause
      mortality as outcome, influenza activity and extreme temperatures as explanatory
      variables while adjusting for time trend and seasonality. Three indicators of
      weekly influenza activity (IA) were explored: percentage of consultations for
      influenza-like illness (ILI) at primary health care, national percentage of
      influenza-positive samples, and the product of ILI percentage and percentage of
      influenza-positive specimens in a given week, that is, the Goldstein index.
      RESULTS: Independent of the choice of parameter to represent influenza activity,
      the estimated influenza-associated mortality showed similar patterns with the
      Goldstein index being the most conservative. Over the 7 winter seasons, the
      median influenza-associated mortality per 100 000 population was 17.6 (range: 0.0
      36.8), 14.1 (0.3-31.6) and 8.3 (0.0-25.0) for the 3 indicators, respectively, for
      all ages. CONCLUSION: The FluMOMO model fitted the Danish data well and has the
      potential to estimate all-cause influenza-associated mortality in near real time
      and could be used as a standardised method in other countries. We recommend using
      the Goldstein index as the influenza activity indicator in the FluMOMO model.
      Further work is needed to improve the interpretation of the estimated effects.

PMID- 29660771
TI  - Integrated approach to oral health in aged care facilities using oral health
      practitioners and teledentistry in rural Queensland.
AB  - PROBLEM: Residents of residential aged care facilities are at very high risk of
      developing complex oral diseases and dental problems. Key barriers exist in
      delivering oral health services to residential aged care facilities, particularly
      in regional and rural areas. DESIGN: A quality improvement study incorporating
      pre- and post chart audits and pre- and post consultation with key stakeholders,
      including staff and residents, expert opinion on cost estimates and field notes
      were used. SETTING: One regional and three rural residential aged care facilities
      situated in a non-metropolitan hospital and health service in Queensland. KEY
      MEASURES FOR IMPROVEMENT: Number of appointments avoided at an oral health
      facility Feedback on program experience by staff and residents Compliance with
      oral health care plan implementation Observations of costs involved to deliver
      new service. STRATEGIES FOR CHANGE: The model developed incorporated a visit by
      an oral health therapist for screening, education, simple intervention and
      referral for a teledentistry session if required. EFFECTS OF CHANGE: Results
      showed an improvement in implementation of oral health care plans and a
      minimisation of need for residents to attend an oral health care facility.
      Potential financial and social cost savings for residents and the facilities were
      also noted. LESSONS LEARNT: Screening via the oral health therapist and
      teledentistry appointment minimises the need for a visit to an oral health
      facility and subsequent disruption to residents in residential aged care
      facilities.

PMID- 29660770
TI  - Psychological therapy for inpatients receiving acute mental health care: A
      systematic review and meta-analysis of controlled trials.
AB  - OBJECTIVES: The effectiveness of psychological therapies for those receiving
      acute adult mental health inpatient care remains unclear, partly because of the
      difficulty in conducting randomized controlled trials (RCTs) in this setting. The
      aim of this meta-analysis was to synthesize evidence from all controlled trials
      of psychological therapy carried out with this group, to estimate its effects on
      a number of important outcomes and examine whether the presence of randomization
      and rater blinding moderated these estimates. METHOD: A systematic review and
      meta-analysis of all controlled trials of psychological therapy delivered in
      acute inpatient settings was conducted, with a focus on psychotic symptoms,
      readmissions or emotional distress (anxiety and depression). Studies were
      identified through ASSIA, EMBASE, CINAHL, Cochrane, MEDLINE, and PsycINFO using a
      combination of the key terms 'inpatient', 'psychological therapy', and 'acute'.
      No restriction was placed on diagnosis. The moderating effect of the use of
      assessor-blind RCT methodology was examined via subgroup and sensitivity
      analyses. RESULTS: Overall, psychological therapy was associated with small-to
      moderate improvements in psychotic symptoms at end of therapy but the effect was
      smaller and not significant at follow-up. Psychological therapy was also
      associated with reduced readmissions, depression, and anxiety. The use of single
      blind randomized controlled trial methodology was associated with significantly
      reduced benefits on psychotic symptoms and was also associated with reduced
      benefits on readmission and depression; however, these reductions were not
      statistically significant. CONCLUSIONS: The provision of psychological therapy to
      acute psychiatric inpatients is associated with improvements; however, the use of
      single-blind RCT methodology was associated with reduced therapy-attributable
      improvements. Whether this is a consequence of increased internal validity or
      reduced external validity is unclear. Trials with both high internal and external
      validity are now required to establish what type, format, and intensity of brief
      psychological therapy is required to achieve sustained benefits. PRACTITIONER
      POINTS: Clinical implications: This review provides the first meta-analytical
      synthesis of brief psychological therapy delivered in acute psychiatric inpatient
      settings. This review suggests that brief psychological therapy may be associated
      with reduced emotional distress and readmissions. LIMITATIONS: The evidence in
      this review is of limited quality. The type, format, and intensity of brief
      psychological therapy required to achieve sustained benefits are yet to be
      established.

PMID- 29660772
TI  - Human factors enablers and barriers for successful airway management - an in
      depth interview study.
AB  - Human factors are the individual, team, environmental and organisational aspects
      of the anaesthetic environment that affect performance and decision-making of
      anaesthesia teams. This study aimed to identify which human factors were enablers
      and/or barriers to anaesthesia teams during airway management challenges. Sixteen
      interviews were conducted with experienced anaesthetists and anaesthetic nurses
      using an in-depth interview technique (the Critical Decision Method) to identify
      human factors enablers and/or barriers during successful management of a
      significant airway challenge. Thematic analysis identified three overarching
      enablers: equipment location and storage; experience and learning; teamwork and
      communication. Five overarching barriers were also identified: time and resource
      limitations; teamwork and communication; equipment location and storage;
      experience and learning; insufficient back-up planning; and equipment
      preparation. This study showed that a variety of human factors issues affect the
      handling of airway challenges, ranging from individual and team to organisational
      and environmental aspects. Recommendations for the design of airway management
      decision support tools that relate to equipment standardisation, decision support
      complexity, inclusive mutual learning and teamwork are discussed.

PMID- 29660774
TI  - Intrapersonal Emotion Regulation Processes Influence What Children Remember About
      Their Emotional Experiences.
AB  - Little work has tested how emotion regulation (ER) processes influence children's
      memory for negative experiences. We investigated how two intrapersonal ER
      processes (affect-biased attention and changes in negative feelings) predicted
      children's (N = 184, 93 girls, ages 3-11) memory. Recall of a sad or scary film
      was tested after a delay. The way discrete emotional information was remembered
      varied with ER and children's age. Older children with greater affect-biased
      attention or less reduction of fear demonstrated privileged memory for central
      information from the scary film. Older children with greater affect-biased
      attention but greater reductions in sadness recalled more from the sad film
      overall. Findings suggest ER processes should be considered when examining
      children's memory for negative emotional information.

PMID- 29660773
TI  - Active Chicken Meat Packaging Based on Polylactide Films and Bimetallic Ag-Cu
      Nanoparticles and Essential Oil.
AB  - : Plasticized polylactide (PLA) composite films with multifunctional properties
      were created by loading bimetallic silver-copper (Ag-Cu) nanoparticles (NPs) and
      cinnamon essential oil (CEO) into polymer matrix via compression molding
      technique. Rheological, structural, thermal, barrier, and antimicrobial
      properties of the produced films, and its utilization in the packaging of chicken
      meat were investigated. PLA/PEG/Ag-Cu/CEO composites showed a very complex
      rheological system where both plasticizing and antiplasticizing effects were
      evident. Thermal properties of plasticized PLA film with polyethylene glycol
      (PEG) enhanced considerably with the reinforcement of NPs whereas loading of CEO
      decreased glass transition, melting, and crystallization temperature. The barrier
      properties of the composite films were reduced with the increase of CEO loading
      (P < 0.05). Their optical properties were also modified by the addition of both
      CEO and Ag-Cu NPs. The changes in the molecular organization of PLA composite
      films were visualized by FTIR spectra. Rough and porous surfaces of the films
      were evident by scanning electron microscopy. The effectiveness of composite
      films was tested against Salmonella Typhimurium, Campylobacter jejuni and
      Listeria monocytogenes inoculated in chicken samples, and it was found that the
      films loaded with Ag-Cu NPs and 50% CEO showed maximum antibacterial action
      during 21 days at the refrigerated condition. The produced PLA/Ag-Cu/CEO
      composite films can be applied to active food packaging. PRACTICAL APPLICATION:
      The nanoparticles and essential oil loaded PLA composite films are capable of
      exhibiting antimicrobial effects against Gram (+) and (-) bacteria, and extend
      the shelf-life of chicken meat. The bionanocomposite films showed the potential
      to be manufactured commercially because of the thermal stability of the active
      components during the hot-press compression molding process. The developed
      bionanocomposites could have practical importance and open a new direction for
      the active food packaging to control the spoilage and the pathogenic bacteria
      associated with the fresh chicken meat.

PMID- 29660775
TI  - Baseline neutrophil-to-lymphocyte ratio in patients with advanced melanoma
      treated with immune checkpoint inhibitors.

PMID- 29660776
TI  - Correlation Between Acetogenin Content and Antiproliferative Activity of Pawpaw
      (Asimina triloba [L.] Dunal) Fruit Pulp Grown in Korea.
AB  - : Pawpaw (Asimina triloba [L.] Dunal) is widely cultivated in Korea for its
      fruit, which contains bioactive compounds, such as acetogenins. In this study, we
      investigated the acetogenin content and antiproliferative activity of pawpaw
      fruit pulp against various cancer cell lines and evaluated the relationship
      between these two variables at different maturation stages. Unripe fruit had
      higher antiproliferative activity than ripe fruit, and the activity level
      depended on acetogenin content. In addition, the presence of specific acetogenins
      was related to inhibition of certain cancer cell types. The unripe fruit methanol
      and ethanol extracts (URFM and URFE, respectively) that were rich in acetogenins
      strongly inhibited the growth of HT-1080, HeLa, and AGS cells by >50% at
      concentrations of less than 115 MUg/mL. These findings indicate that URFM and
      URFE have therapeutic potential for the treatment of cancer, and our study
      establishes a basis for further mechanistic studies of the antiproliferative
      activity of pawpaw fruit. However, it is necessary to further study the
      anticancer activity of acetogenins from pawpaw fruit using in vivo activity
      approaches. PRACTICAL APPLICATION: Pawpaw (Asimina triloba) contains acetogenins
      that can inhibit the growth of cancer cells. In our study, we demonstrate that
      the antiproliferative activity is higher in unripe than in ripe fruit and depends
      on acetogenin content. Our results indicate that the extract of unripe pawpaw
      fruit has value not only as a functional food, but has therapeutic potential for
      the treatment of cancer as a naturally derived substance that may be less toxic
      than conventional chemotherapy drugs.

PMID- 29660778
TI  - Injection of Natural Protease Inhibitors and Evaluation of Their Impact on Cooked
      Pacific Whiting (Merluccius productus) Fillets.
AB  - : Brine injection of natural proteases, dried egg white (EW), and dried potato
      extract (PE), was investigated as a means to prevent softening during cooking of
      Pacific whiting fillets. Treatments included fillets injected with Water (W), 3%
      sodium chloride and 3% sodium tripolyphosphate brine (B), B with 0.1% xanthan gum
      (BXG ), B with 1%, 2%, or 3% EW (B1-3EW ), B with 1%, 2%, or 3% PE (B1-3PE ) or
      non-injected (NI). Non-injected Pacific cod (Cod) was also utilized as a
      reference for texture analysis. Fillets were subsequently cooked using cooking
      protocol 1 (90  degrees C for 20 min) or cooking protocol 2 (60  degrees C for 30
      min then 90  degrees C for 20 min). Cooked fillet pH, moisture, total protein,
      total extractable protein (TEP), total non-extractable protein (TNEP), texture
      profile analysis (TPA), and electrophoretic pattern (SDS-PAGE) were measured.
      Cooking protocol 2 significantly reduced moisture, increased total protein, TEP
      and TNEP. Loss of moisture suggested cooking protocol 2 promoted proteolysis.
      Electrophoretic evaluations of the fillets treated with the cooking protocol 2
      confirmed proteolysis was enhanced by cooking protocol 2 and myosin band
      integrity was protected in fillets containing natural protease inhibitors. For
      TPA, there was no significant difference between protease inhibitor types
      although means for BEW did trend higher than BPE . However, PCA analysis clearly
      demonstrated B2EW and B3EW fillets were most similar to Cod. Results demonstrated
      brine injection with protease inhibitors prevented fillet softening during
      cooking. PRACTICAL APPLICATION: Texture softening in fish has typically been
      addressed by diverting product to lower-value minced applications where
      ingredients can be blended-in to counteract softening caused by enzymes.
      Investigations demonstrate feasibility of brine injection of protease inhibitor
      ingredient, dried egg white, to preserve protein integrity during cooking. Dried
      potato extract required a suspension aide, xanthan gum, in order to become
      sufficiently suspended in the brine for injection. Dried potato extract was able
      to inhibit protease activity, however, the suspension aide negatively impacted
      protein-protein interactions during cooking. An alternative suspension aide is
      therefore required for dried potato extract.

PMID- 29660777
TI  - Clinical and Functional Relevance of the Monocarboxylate Transporter Family in
      Disease Pathophysiology and Drug Therapy.
AB  - The solute carrier (SLC) SLC16 gene family comprises 14 members and encodes for
      monocarboxylate transporters (MCTs), which mediate the absorption and
      distribution of monocarboxylic compounds across plasma membranes. As the
      knowledge about their physiological function, activity, and regulation increases,
      their involvement and contribution to cancer and other diseases become
      increasingly evident. Moreover, promising opportunities for therapeutic
      interventions by directly targeting their endogenous functions or by exploiting
      their ability to deliver drugs to specific organ sites emerge.

PMID- 29660779
TI  - Clinical findings and diagnostic procedures in 270 small ruminants with
      obstructive urolithiasis.
AB  - BACKGROUND: Details of the clinical signs of obstructive urolithiasis in male
      small ruminants have not been documented in a large population. OBJECTIVE: To
      describe the clinical presentation and diagnostic procedures in a large group of
      small ruminants with urolithiasis. ANIMALS: Two hundred and seventy small
      ruminants (158 sheep and 112 goats). METHODS: Retrospective study of 270 cases
      identified based on clinical records. RESULTS: 81.2% affected goats were
      castrated and 91.7% sheep were intact males; 65.5% of the animals had been sick
      <=2 days before referral. Common abnormalities included dysuria (93.6%),
      indigestion (84.4%), reduced general state of health (79.5%), signs of pain
      (73%), increased heart and respiratory rates (53.6% and 39.1%), and azotemia
      (89.4%). Blood urea nitrogen (BUN) and creatinine concentrations were strongly
      correlated (r2  = 0.81). Hypochloremia (52.2%), hyponatremia (43.3%),
      hypophosphatemia (52.4%), and abnormal potassium concentrations (26.2%
      hypokalemia and 24.5% hyperkalemia) were the most common serum electrolyte
      imbalances. Packed cell volume (PCV), plasma proteins, potassium, BUN, and
      creatinine concentrations were significantly increased in animals with
      uroperitoneum. Ultrasonography allowed for confirmation of diagnosis in 83.9% of
      the cases (135/161 with sufficient available information), uroliths were visible
      on 34 of 56 plain radiographs. CONCLUSIONS AND CLINICAL IMPORTANCE: Our study
      confirmed that clinical and ultrasonographic examinations are sufficient to
      diagnose urolithiasis. Clinical signs can be divided into an early stage with
      discrete unspecific clinical signs, a painful stage with frequent straining,
      expression of pain and moderately reduced general condition, and an advanced
      stage with a markedly reduced general condition and eventually recumbency.

PMID- 29660780
TI  - Steroid-Based Amphiphiles for Membrane Protein Study: The Importance of Alkyl
      Spacers for Protein Stability.
AB  - Membrane proteins allow effective communication between cells and organelles and
      their external environments. Maintaining membrane protein stability in a non
      native environment is the major bottleneck to their structural study. Detergents
      are widely used to extract membrane proteins from the membrane and to keep the
      extracted protein in a stable state for downstream characterisation. In this
      study, three sets of steroid-based amphiphiles-glyco-diosgenin analogues (GDNs)
      and steroid-based pentasaccharides either lacking a linker (SPSs) or containing a
      linker (SPS-Ls)-have been developed as new chemical tools for membrane protein
      research. These detergents were tested with three membrane proteins in order to
      characterise their ability to extract membrane proteins from the membrane and to
      stabilise membrane proteins long-term. Some of the detergents, particularly the
      SPS-Ls, displayed favourable behaviour with the tested membrane proteins. This
      result indicates the potential utility of these detergents as chemical tools for
      membrane protein structural study and a critical role of the simple alkyl spacer
      in determining detergent efficacy.

PMID- 29660781
TI  - Effects of Site and Cultivar on Consumer Acceptance of Pomegranate.
AB  - : Pomegranate (Punica granatum L.) is an important fruit in many cultures. The
      fruit and juice have risen in popularity as it was discovered that pomegranate
      has relatively high antioxidant activity compared to most other fruits. In this
      study, six cultivars were utilized to determine consumer acceptance compared to
      the industry standard, 'Wonderful,' which comprises 90% to 95% of commercial
      production in the United States. Fruit were sourced from 2 cultivar field trials,
      one in inland Riverside, California, and one in coastal Ventura County,
      California. Cultivars selected for the study included 'Eversweet,' 'Green Globe,'
      'Haku Botan,' 'Loffani,' 'Phoenicia,' 'Wonderful,' and 'cv. 857,' an heirloom
      cultivar from Ventura County, CA, U.S.A. Pomegranate arils were subject to
      sensory evaluation by 87 untrained consumer panelists in late 2016. Panelists
      were given pomegranate arils and asked to score the samples using a 9-point
      Hedonic scale for the following fruit quality traits: aril color, sweetness,
      tartness, seed hardness, bitterness, and overall desirability. There were
      significant differences among cultivars for all traits assessed by the sensory
      panelists. There were differences in acceptance among consumers for 'Wonderful'
      depending on if it was grown on the coast versus inland, and consumers preferred
      inland- versus coastal-grown 'Wonderful.' 'Wonderful' pomegranate was associated
      with cultivars that consumers scored low on desirability for bitterness.
      Cultivars that scored well in overall desirability compared with 'Wonderful' were
      'cv. 857,' 'Eversweet,' 'Green Globe,' and 'Phoenicia.' PRACTICAL APPLICATION:
      Consumer sensory panels are important to determine scientifically which cultivars
      are desired by the public. These panels allowed for the determination of which
      pomegranate cultivars are liked or disliked by consumers and why. If the
      pomegranate growers know the most desirable cultivars for consumers, they are
      more likely to adopt and plant them, thus potentially increasing the diversity in
      the marketplace, as has been with apples, peaches, plums, pears, mangoes,
      strawberries, raspberries, blueberries, and citrus.

PMID- 29660782
TI  - Sodium-glucose cotransporter 2 inhibitor-induced changes in body composition and
      simultaneous changes in metabolic profile: 52-week prospective LIGHT
      (Luseogliflozin: the Components of Weight Loss in Japanese Patients with Type 2
      Diabetes Mellitus) Study.
AB  - AIMS/INTRODUCTION: It is unclear how changes in body composition induced by
      sodium-glucose cotransporter 2 (SGLT2) inhibitor treatment correlate with
      metabolic profile changes. We aimed to clarify how metabolic profile changes
      correlate with body component changes, and if SGLT2 inhibitor treatment causes
      sarcopenia and bone mineral content (BMC) loss. MATERIALS AND METHODS: Moderately
      obese Japanese type 2 diabetes patients, treated with luseogliflozin for a year,
      were observed prospectively and evaluated for body composition changes. We
      analyzed the changes in the individual body components during treatment, and
      their correlation with other clinical variables. RESULTS: The efficacy analysis
      set comprised 37 of 43 enrolled patients. The total fat mass significantly
      decreased early in the treatment at and after week 4, with a mean decrease of 
      1.97 kg (95% confidence interval -2.66 to -1.28) at week 24. The visceral fat
      area at week 24 showed an average downward trend, although this was not
      significant. The changes in visceral fat area in individual patients showed a
      significant negative correlation with the extent of the baseline visceral fat
      area (r = -0.399, P = 0.023). The skeletal muscle mass index showed a significant
      but small change at and after week 36. The BMC profile showed a transient
      significant decrease only at week 12. No significant change in BMC was noted at
      other time-points. CONCLUSIONS: Luseogliflozin treatment brought about favorable
      changes in body composition and metabolism of moderately obese Japanese type 2
      diabetes patients, accompanied by body fat reduction, and minimal muscle and BMC
      reduction.

PMID- 29660783
TI  - Contribution of 2-Propenesulfenic Acid to the Antioxidant Activity of Allicin.
AB  - : We re-examined the antioxidative mechanism of allicin as a radical scavenger on
      the basis of the reactivity toward 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and
      peroxyl radicals. Initially, it was found that allicin decomposed more rapidly in
      n-hexane and chlorobenzene than in acetonitrile, ethanol, and ethanol/water
      solutions and decomposed into ajoene and vinyldithiins in these solvents.
      Furthermore, the decomposition of allicin and the following formations of ajoene
      and vinyldithiins from allicin were accelerated by the reaction of allicin with
      DPPH and peroxyl radicals. These results show that 2-propenesulfenic acid, which
      arises by Cope elimination from allicin, is proposed to contribute to scavenge
      these radicals because ajoene and vinyldithiins were produced from allicin
      through the use of 2-propenesulfenic acid. Next, allicin was more effective at
      inhibiting the linoleic acid oxidation at 50  degrees C than at 30  degrees C and
      in cyclohexane than in acetonitrile. These results indicate that allicin
      decomposed rapidly at high temperatures in a hydrogen-bond-acceptor solution to 2
      propenesulfenic acid. In addition, 2-propene-1-sulfinothionic acid S-methyl
      ester, which does not produce sulfenic acid through Cope elimination, has no
      activity against the radicals. On the other hand, methanesulfinothionic acid S-2
      propenyl ester, which produces methanesulfenic acid through Cope elimination, has
      the same or increased activity as its allicin against the radicals. Based on
      these results, the Cope elimination product, sulfenic acid, from thiosulfinates
      with an alpha-sulfenyl proton was found to make a larger contribution to the
      radical scavenger than that of allicin itself. PRACTICAL APPLICATION: We examined
      the antioxidant activity of allicin on the oxidation of cumene and linoleic acid
      in homogeneous solutions. It is obvious from these results that 2-propenesulfenic
      acid was found to make a larger contribution to the radical scavenger than that
      of allicin itself.

PMID- 29660784
TI  - Relationship between neural crest cell specification and rare ocular diseases.
AB  - Development of the eye is closely associated with neural crest cell migration and
      specification. Eye development is extremely complex, as it requires the working
      of a combination of local factors, receptors, inductors, and signaling
      interactions between tissues such as the optic cup and periocular mesenchyme
      (POM). The POM is comprised of neural crest-derived mesenchymal progenitor cells
      that give rise to numerous important ocular structures including those tissues
      that form the optic cup and anterior segment of the eye. A number of genes are
      involved in the migration and specification of the POM such as PITX2, PITX3,
      FOXC1, FOXE3, PAX6, LMX1B, GPR48, TFAP2A, and TFAP2B. In this review, we will
      discuss the relevance of these genes in the development of the POM and how
      mutations and defects result in rare ocular diseases.

PMID- 29660785
TI  - Integrated Population Pharmacokinetic Analysis of Rivaroxaban Across Multiple
      Patient Populations.
AB  - The population pharmacokinetics (PK) of rivaroxaban have been evaluated in
      several population-specific models. We developed an integrated population PK
      model using pooled data from 4,918 patients in 7 clinical trials across all
      approved indications. Effects of gender, age, and weight on apparent clearance
      (CL/F) and apparent volume of distribution (V/F), renal function, and
      comedication on CL/F, and relative bioavailability as a function of dose (F) were
      analyzed. Virtual subpopulations for exposure simulations were defined by age,
      creatinine clearance (CrCL) and body mass index (BMI). Rivaroxaban PK were
      adequately described by a one-compartment disposition model with a first-order
      absorption rate constant. Significant effects of CrCL, use of comedications, and
      study population on CL/F, age, weight, and gender on V/F, and dose on F were
      identified. CrCL had a modest influence on exposure, whereas age and BMI had a
      minor influence. The model was suitable to predict rivaroxaban exposure in
      patient subgroups of special interest.

PMID- 29660786
TI  - Activity and selectivity cliffs for DPP-IV inhibitors: Lessons we can learn from
      SAR studies and their application to virtual screening.
AB  - The inhibition of dipeptidyl peptidase-IV (DPP-IV) has emerged over the last
      decade as one of the most effective treatments for type 2 diabetes mellitus, and
      consequently (a) 11 DPP-IV inhibitors have been on the market since 2006 (three
      in 2015), and (b) 74 noncovalent complexes involving human DPP-IV and drug-like
      inhibitors are available at the Protein Data Bank (PDB). The present review aims
      to (a) explain the most important activity cliffs for DPP-IV noncovalent
      inhibition according to the binding site structure of DPP-IV, (b) explain the
      most important selectivity cliffs for DPP-IV noncovalent inhibition in comparison
      with other related enzymes (i.e., DPP8 and DPP9), and (c) use the information
      deriving from this activity/selectivity cliff analysis to suggest how virtual
      screening protocols might be improved to favor the early identification of potent
      and selective DPP-IV inhibitors in molecular databases (because they have not
      succeeded in identifying selective DPP-IV inhibitors with IC50 <= 100 nM). All
      these goals are achieved with the help of available homology models for DPP8 and
      DPP9 and an analysis of the structure-activity studies used to develop the
      noncovalent inhibitors that form part of some of the complexes with human DPP-IV
      available at the PDB.

PMID- 29660788
TI  - Melancholia and cancer: The bladder cancer narrative.

PMID- 29660789
TI  - Evaluation of Chilling Injury in Mangoes Using Multispectral Imaging.
AB  - : Commodities originating from tropical and subtropical climes are prone to
      chilling injury (CI). This injury could affect the quality and marketing
      potential of mango after harvest. This will later affect the quality of the
      produce and subsequent consumer acceptance. In this study, the appearance of CI
      symptoms in mango was evaluated non-destructively using multispectral imaging.
      The fruit were stored at 4  degrees C to induce CI and 12  degrees C to preserve
      the quality of the control samples for 4 days before they were taken out and
      stored at ambient temperature for 24 hr. Measurements using multispectral imaging
      and standard reference methods were conducted before and after storage. The
      performance of multispectral imaging was compared using standard reference
      properties including moisture content (MC), total soluble solids (TSS) content,
      firmness, pH, and color. Least square support vector machine (LS-SVM) combined
      with principal component analysis (PCA) were used to discriminate CI samples with
      those of control and before storage, respectively. The statistical results
      demonstrated significant changes in the reference quality properties of samples
      before and after storage. The results also revealed that multispectral parameters
      have a strong correlation with the reference parameters of L* , a* , TSS, and MC.
      The MC and L* were found to be the best reference parameters in identifying the
      severity of CI in mangoes. PCA and LS-SVM analysis indicated that the fruit were
      successfully classified into their categories, that is, before storage, control,
      and CI. This indicated that the multispectral imaging technique is feasible for
      detecting CI in mangoes during postharvest storage and processing. PRACTICAL
      APPLICATION: This paper demonstrates a fast, easy, and accurate method of
      identifying the effect of cold storage on mango, nondestructively. The method
      presented in this paper can be used industrially to efficiently differentiate
      different fruits from each other after low temperature storage.

PMID- 29660787
TI  - High G2 and S-phase expressed 1 expression promotes acral melanoma progression
      and correlates with poor clinical prognosis.
AB  - G2 and S-phase expressed 1 (GTSE1) regulates cell cycle progression in human
      cancers. However, its significance and mechanism of action in acral melanoma (AM)
      remain unknown. In the present study, we found that GTSE1 expression was
      upregulated in advanced stage/metastatic AM tissues and metastatic cell lines,
      and correlated with higher stage (P = .028) and poor disease-free survival (DFS)
      in patients with AM (P = .003). Cox regression assays validated GTSE1 expression
      to be an independent prognostic factor of DFS for patients with AM (P = .004).
      Ectopic expression of GTSE1 enhanced primary AM cell proliferation, invasion, and
      migration. Loss-of-function in GTSE1 attenuated metastatic AM cell proliferation
      and metastatic ability in vitro and in vivo. We additionally observed that
      inhibition of migration and invasion occurred concomitantly with a GTSE1
      knockdown-mediated increase in E-cadherin and decreases in N-cadherin and Slug.
      We further showed that integrin subunit alpha 2 (ITGA2) interacts with GTSE1 and
      is a downstream effector of GTSE1. Further, ITGA2 levels were positively
      correlated with GTSE1 expression in human AM tissues. Ectopic ITGA2 expression
      rescued siGTSE1-mediated inhibition of migration and invasion, thereby restoring
      epithelial-to-mesenchymal transition (EMT). In conclusion, GTSE1 expression
      promotes AM progression and correlates with clinical outcomes of patients with
      AM, and may represent a promising therapeutic target to suppress AM progression.

PMID- 29660790
TI  - Development of a Tissue-Engineered Artificial Ligament: Reconstruction of Injured
      Rabbit Medial Collateral Ligament With Elastin-Collagen and Ligament Cell
      Composite Artificial Ligament.
AB  - Ligament reconstruction using a tissue-engineered artificial ligament (TEAL)
      requires regeneration of the ligament-bone junction such that fixation devices
      such as screws and end buttons do not have to be used. The objective of this
      study was to develop a TEAL consisting of elastin-coated polydioxanone (PDS)
      sutures covered with elastin and collagen fibers preseeded with ligament cells.
      In a pilot study, a ring-type PDS suture with a 2.5 mm (width) bone insertion was
      constructed with/without elastin coating (Ela-coat and Non-coat) and implanted
      into two bone tunnels, diameter 2.4 mm, in the rabbit tibia (6 cases each) to
      access the effect of elastin on the bond strength. PDS specimens taken together
      with the tibia at 6 weeks after implantation indicated growth of bone-like hard
      tissues around bone tunnels accompanied with narrowing of the tunnels in the Ela
      coat group and not in the Non-coat group. The drawout load of the Ela-coat group
      was significantly higher (28.0 +/- 15.1 N, n = 4) than that of the Non-coat group
      (7.6 +/- 4.6 N, n = 5). These data can improve the mechanical bulk property of
      TEAL through extracellular matrix formation. To achieve this TEAL model, 4.5 *
      106 ligament cells were seeded on elastin and collagen fibers (2.5 cm * 2.5 cm *
      80 um) prior to coil formation around the elastin-coated PDS core sutures having
      ball-shape ends with a diameter of 2.5 mm. Cell-seeded and cell-free TEALs were
      implanted across the femur and the tibia through bone tunnels with a diameter of
      2.4 mm (6 cases each). There was no incidence of TEAL being pulled in 6 weeks.
      Regardless of the remarkable degradation of PDS observed in the cell-seeded
      group, both the elastic modulus and breaking load of the cell-seeded group (n =
      3) were comparable to those of the sham-operation group (n = 8) (elastic modulus:
      15.4 +/- 1.3 MPa and 18.5 +/- 5.7 MPa; breaking load: 73.0 +/- 23.4 N and 104.8
      +/- 21.8 N, respectively) and higher than those of the cell-free group (n = 5)
      (elastic modulus: 5.7 +/- 3.6 MPa; breaking load: 48.1 +/- 11.3 N) accompanied
      with narrowed bone tunnels and cartilage matrix formation. These data suggest
      that elastin increased the bond strength of TEAL and bone. Furthermore, our newly
      developed TEAL from elastin, collagen, and ligament cells maintained the strength
      of the TEAL even if PDS was degraded.

PMID- 29660791
TI  - The effectiveness of the Brush Day and Night programme in improving children's
      toothbrushing knowledge and behaviour.
AB  - BACKGROUND: Regular twice-daily toothbrushing with a fluoridated toothpaste is
      widely recommended for schoolchildren. The '21-day Brush Day and Night (BDN)
      programme' includes an educational approach for children and school staff, with a
      consistent practice of toothbrushing at school for 3 weeks. OBJECTIVE: This study
      aims to evaluate the improvement in oral hygiene knowledge and behaviour in
      schoolchildren involved in BDN, the sustainability of this after 6-12 months, and
      if any particular age group was more receptive to it than others. MATERIALS AND
      METHODS: Ten countries and 7,991 children, 2-12 years old, participated in this
      longitudinal study, with two BDN interventions at the beginning and 6-12 months
      afterward. Data were collected via a self-reported questionnaire at
      baseline/first intervention (T0), 21 days after first intervention (T0D21), at
      the second intervention (T1), and 21 days after second intervention (T1D21).
      Improvement in knowledge and behaviour was compared using the chi-square test
      with an alpha level of 5%. The final data sample of 5,148 schoolchildren was
      evaluated, and the analysis revealed that 25% more of the schoolchildren brushed
      their teeth twice a day after the first intervention. The programme was more
      effective among the 7-9 years age group. The BDN intervention increased brushing
      frequency in children at the first intervention, and this was sustained after 6
      12 months. Therefore, this programme illustrated a sustainable approach to
      improve children's oral health knowledge and behaviour.

PMID- 29660792
TI  - In Vitro Bioaccessibility of Colored Carotenoids in Tomato Derivatives as
      Affected by Ripeness Stage and the Addition of Different Types of Oil.
AB  - : The simultaneous effect of tomato ripeness stage (mature green, pink, and red
      ripe), mechanical processing (dicing and grinding), and oil addition (coconut,
      sunflower, and olive oils) on the amount and bioaccessible fraction of
      carotenoids were evaluated. Tomato products obtained from fruits at the most
      advanced ripeness stage exhibited the greatest values of both concentration and
      bioaccessible fraction of total carotenoids and lycopene. The type of processing
      also exerted an important influence on carotenoids content, as well as on its
      bioaccessibility. Thus, despite the concentration of carotenoids in tomato puree
      significantly decreased (36% to 59%), their bioaccessibility was greater (up to
      2.54-fold increase) than in tomato cubes. Moreover, the addition of oil
      significantly improved the carotenoid bioaccessibility, especially when olive oil
      was added, reaching up to 21-fold increase with respect to samples without oil.
      The results obtained clearly indicate that carotenoids bioaccessibility of tomato
      derivatives was strongly influenced by the ripeness stage of the fruit,
      processing and the addition of oil. PRACTICAL APPLICATION: Bioaccessibility of
      carotenoids is known to be affected by different factors. This study provides
      useful information about the synergic effect of different factors affecting the
      amount and the bioaccessible fraction of carotenoids, especially lycopene, in two
      common tomato derivatives. The findings of this work may contribute to develop
      tomato derivatives with high content of bioaccessible carotenoids, leading to the
      enhancement of their health-promoting properties.

PMID- 29660793
TI  - Structural and molecular dynamics studies of a C1-oxidizing lytic polysaccharide
      monooxygenase from Heterobasidion irregulare reveal amino acids important for
      substrate recognition.
AB  - : Lytic polysaccharide monooxygenases (LPMOs) are a group of recently discovered
      enzymes that play important roles in the decomposition of recalcitrant
      polysaccharides. Here, we report the biochemical, structural, and computational
      characterization of an LPMO from the white-rot fungus Heterobasidion irregulare
      (HiLPMO9B). This enzyme oxidizes cellulose at the C1 carbon of glycosidic
      linkages. The crystal structure of HiLPMO9B was determined at 2.1 A resolution
      using X-ray crystallography. Unlike the majority of the currently available C1
      specific LPMO structures, the HiLPMO9B structure contains an extended L2 loop,
      connecting beta-strands beta2 and beta3 of the beta-sandwich structure. Molecular
      dynamics (MD) simulations suggest roles for both aromatic and acidic residues in
      the substrate binding of HiLPMO9B, with the main contribution from the residues
      located on the extended region of the L2 loop (Tyr20) and the LC loop (Asp205,
      Tyr207, and Glu210). Asp205 and Glu210 were found to be involved in the hydrogen
      bonding with the hydroxyl group of the C6 carbon of glucose moieties directly or
      via a water molecule. Two different binding orientations were observed over the
      course of the MD simulations. In each orientation, the active-site copper of this
      LPMO preferentially skewed toward the pyranose C1 of the glycosidic linkage over
      the targeted glycosidic bond. This study provides additional insight into
      cellulose binding by C1-specific LPMOs, giving a molecular-level picture of
      active site substrate interactions. DATABASE: The atomic coordinates and
      structure factors for HiLPMO9B have been deposited in the Protein Data Bank with
      accession code 5NNS.

PMID- 29660795
TI  - Symptom and function profiles of men with localized prostate cancer.
AB  - BACKGROUND: Men diagnosed with localized prostate cancer seek information on how
      treatment options may impact their health-related quality of life (HRQOL). The
      authors used latent profile analysis (LPA) to group men according to their
      symptom burden and functional status and to identify patient characteristics
      associated with each HRQOL profile. METHODS: Patients completed the Patient
      Reported Outcomes Measurement Information System and the Expanded Prostate Index
      Composite measures 3 months after treatment initiation. Anxiety, depression,
      fatigue, sleep disturbance, pain, diarrhea, urinary obstruction, urinary
      incontinence, erectile function, and sex satisfaction were modeled jointly using
      LPA, and the analysis was adjusted for covariates to examine associations between
      patient characteristics and profiles. RESULTS: One-third of the 373 men were not
      non-Hispanic white (26% were black). Four LPA profiles were identified. Men who
      experienced the "best HRQOL" were less likely to receive treatment, to be older,
      and to smoke. Men in the second best profile experienced symptoms similar to men
      in the best HRQOL group but reported poor sexual and urinary function, because
      they were more likely to receive therapy. The third profile included men with
      increased symptom burden and poor functioning who were likely to undergo
      prostatectomy and to have increased comorbidity. The "worst HRQOL" group
      experienced the worst symptoms and the poorest functioning, and these men were
      more likely to be younger, to have more comorbidities, and to smoke. CONCLUSIONS:
      LPA revealed that men who receive the same treatment can experience very
      different HRQOL impact. Understanding the factors most associated with poorer
      HRQOL allows clinicians to focus their care on individuals most in need of
      symptom management and support. Cancer 2018;124:2832-2840. (c) 2018 American
      Cancer Society.

PMID- 29660794
TI  - Diagnostic utility of cardiac troponin I in cats with hypertrophic
      cardiomyopathy.
AB  - BACKGROUND: Cardiac troponin I (cTnI) is useful for assessing hypertrophic
      cardiomyopathy (HCM) in cats. OBJECTIVE: To measure plasma cTnI concentrations in
      healthy cats and evaluate the clinical utility of cTnI in determining the
      severity of HCM. ANIMALS: Clinically healthy cats (n = 88) and cats with HCM (n =
      93). METHODS: Multicenter prospective study. Cats with HCM, including
      hypertrophic obstructive cardiomyopathy at various stages, were diagnosed using
      echocardiography. Plasma cTnI concentrations were analyzed by a commercial
      laboratory. Receiver-operating characteristic curve analysis was used to evaluate
      the accuracy of plasma cTnI concentrations to detect HCM. RESULTS: The median
      cTnI concentration was 0.027 ng/mL (interquartile range, 0.012-0.048 ng/mL) in
      healthy cats. Concentrations were significantly higher in diseased cats than in
      healthy controls, and concentrations were significantly higher in cats with heart
      failure than in asymptomatic cats. A plasma cTnI concentration of 0.163 ng/mL had
      a sensitivity of 62.0% and specificity of 100% when used to distinguish normal
      cats from asymptomatic HCM cats without left atrial dilatation. A cutoff of 0.234
      ng/mL had high sensitivity (95.0%) and specificity (77.8%) for assessing heart
      failure. The areas under the receiver-operating characteristic curves were 0.85
      and 0.93, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Increased cTnI
      concentrations reflect the severity of HCM. If other causes of cardiac injury are
      ruled out, plasma cTnI concentration may be useful for predicting the severity of
      HCM in cats.

PMID- 29660796
TI  - Mechanistic and structural insights into the in vitro inhibitory action of
      hypericin on glutathione reductase purified from baker's yeast.
AB  - This work aims at studying the interaction between glutathione reductase (GR) and
      hypericin. The type of inhibition was determined by measuring changes in GR
      activity at increasing concentrations of hypericin as well as at varying
      concentrations of glutathione disulfide (GSSG) and nicotinamide adenine
      dinucleotide phosphate (NADPH), and the binding pose of hypericin was predicted
      by molecular docking. Accordingly, hypericin emerges as an effective inhibitor of
      GR. When the variable substrate is GSSG, the type of inhibition is competitive.
      When the variable substrate is NADPH, however, the type of inhibition appears to
      be linear mixed-type competitive. Our computational analyses suggest that
      hypericin binds in the large intermonomer cavity of GR, and that it may interfere
      with the normal positioning/functioning of the redox-active disulfide center at
      the enzyme's active site. Overall, besides its contributory role in promoting
      oxidative stress via the formation of reactive oxygen species in photodynamic
      therapy, hypericin can also weaken cancer cells through inhibiting GR.

PMID- 29660798
TI  - Dynamics and Rigidity of an Intact Filamentous Bacteriophage Virus Probed by
      Magic Angle Spinning NMR.
AB  - The capsid dynamics of filamentous bacteriophages is related to their function,
      stability, and interactions with the genome, and can be assessed by measuring the
      chemical shift anisotropy (CSA) of 15 N amides, which are sensitive to large
      amplitude motions. In this study, CSA recoupling experiments under magic-angle
      spinning NMR were used to probe the dynamics of the y21m capsid mutant of fd
      bacteriophage. Based on fitting the generated CSA lineshapes, residues located in
      the N-terminus undergo increased motional amplitudes suggesting its global
      motion, whereas other backbone residues are rigid, and imply a tight hydrophobic
      packing of the phage.

PMID- 29660797
TI  - Repair of a Giant Omphalocele in an Infant With a Pericardial Implant Crosslinked
      With Oligourethane.
AB  - The giant omphalocele (GO) represents a challenge for the pediatric surgeon in
      its management and wall abdominoplasty. Here, we report the outcome of a case in
      which a GO in a newborn patient was repaired with an implant derived from
      decellularized bovine pericardium crosslinked with oligourethane. The
      implantation time was extended for 6 months. This was then followed up by the
      retrieval of the implant and the subsequent reconstruction in a second surgical
      time by the closure of the abdominal wall fascia. A short hospital stay, early
      integration into the patient's family environment, as well as early onset of the
      oral route without special care of the implant or reconstructed wall nor food
      restrictions were observed. The reduced presence of the complications described
      in the literature after application of surgical meshes suggests that this implant
      can be an effective and safe alternative method in the treatment of abdominal
      wall defects such as GO.

PMID- 29660799
TI  - Efficient CO2 Insertion and Reduction Catalyzed by a Terminal Zinc Hydride
      Complex.
AB  - The terminal zinc hydride complex [Tntm]ZnH (2; Tntm=tris(6-tert-butyl-3
      thiopyridazinyl)methanide) is an efficient hydrosilylation catalyst of CO2 at
      room temperature without the need of Lewis acidic additives. The inherent
      electrophilicity of the system leads to selective formation of the monosilylated
      product (MeO)3 SiO2 CH (at room temperature with a TOF of 22.2 h-1 and at 45 
      degrees C with a TOF of 66.7 h-1 ). In absence of silanes, the intermediate
      formate complex [Tntm]Zn(O2 CH) (3) is quantitatively formed within 5 min. All
      complexes were fully characterized by 1 H and 13 C NMR spectroscopy and single
      crystal X-ray diffraction analyses. Density functional theory (DFT) calculations
      reveal a high positive charge on zinc and the increased preference of the ligand
      to adopt a kappa3 -coordination mode.

PMID- 29660801
TI  - Evaluation of long-term effects of artificial sweeteners on rat brain: a
      biochemical, behavioral, and histological study.
AB  - The aim of the present study was to compare the effects of artificial sweeteners
      (aspartame, saccharin, and sucralose) on rat brain. Twenty-four adult male
      Sprague-Dawley rats were included in the study. The control group (n = 6)
      received regular tap water, whereas other groups received aspartame (3 mg/kg/day,
      n = 6,) or saccharin (3 mg/kg/day, n = 6) or sucralose (1.5 mg/kg/day, n = 6) in
      the drinking water. Following 6 weeks, the passive avoidance learning (PAL) test
      was performed to evaluate the neurobehavioral effects of sweeteners. The brains
      were assessed for lipid peroxides, neuron count, and Glial fibrillary acidic
      protein (GFAP) immunohistochemistry. Our results demonstrated that chronic intake
      of sweeteners significantly impaired PAL performance in all groups. Hippocampal
      CA1-CA3 areas revealed significantly lower neuronal count in aspartame and
      increased GFAP expression in all groups. Brain lipid peroxides were significantly
      higher in all groups. Our findings suggest that long-term consumption of
      artificial sweeteners may have harmful effects on cognition and hippocampal
      integrity in rats.

PMID- 29660800
TI  - Physicochemical Quality, Fatty Acid Composition, and Sensory Analysis of Nellore
      Steers Meat Fed with Inclusion of Condensed Tannin in the Diet.
AB  - : This study was conducted to test the effect of dietary tannin on the fatty acid
      profile and sensory attributes of meat from Nellore steers. Thirty-two Nellore
      bull male were distributed in a completely randomized design and fed diets with
      condensed tannin extract as follows: 0, 10, 30, and 50 g/kg total DM basis. The
      physicochemical composition of the meat, lipid oxidation, fatty acid profile,
      flavor, tenderness, and overall acceptance were evaluated. There was a linear
      decrease (P <= 0.05) on lipid content, tenderness, cooking weight loss, myristic,
      palmitic, and oleic acids in meat as tannin increased in the diets. The total
      saturated and monounsaturated fatty acids, the atherogenicity index decreased.
      However, a linear increase (P <= 0.05) was observed for linoleic, linolenic,
      arachidonic, eicosapentaenoic, and docosapentaenoic acids. The physicochemical
      characteristic of the meat, such as moisture, ash, and protein contents, water
      retention capacity, final pH, Warner-Bratzler shear force, collagen, and color
      indexes (lightness, redness, yellowness, and chrome) did not change with dietary
      tannin. Also, CLA, n-6:n-3 ratio, Delta9 -desaturase, and elongase activity were
      not different among diets. In conclusion, condensed tannin linearly increases
      unsaturated fatty acids and decreases the atherogenicity index of meat; thus, it
      can be recommended at the highest level (50 g/kg DM) in the diet of Nellore
      steers. PRACTICAL APPLICATION: Agriculture byproducts plays an important part in
      the diet of ruminant animals and consequently on food chain and has implications
      for the composition and quality of the livestock products (milk, meat, and eggs)
      that people consume. Feeding tannin to steers increases the amount of unsaturated
      fatty acids and meat tenderness, with a concomitant reduction on saturated fatty
      acids and the atherogenicity index in meat. Thus, we recommend adding tannin to
      steer diets to reduce the risk factors for cardiovascular diseases in red meat
      for human consumption.

PMID- 29660802
TI  - Flexible Fe2 O3 and V2 O5 Nanofibers as Binder-Free Electrodes for High
      Performance All-Solid-State Asymmetric Supercapacitors.
AB  - Flexible, highly porous Fe2 O3 and V2 O5 nanofibers (NFs) have been synthesized
      by a facile electrospinning method followed by calcination. They have been
      directly used as binder-free electrodes for high-performance supercapacitors.
      These Fe2 O3 and V2 O5 NFs interconnect with one another and construct three
      dimensional hierarchical porous films with high specific surface areas.
      Benefitting from their unique structural features, binder-free Fe2 O3 and V2 O5
      porous nanofiber electrodes offer high specific capacitances of 255 F g-1 and 256
      F g-1 , respectively, at 2 mV s-1 in 1 m aqueous Na2 SO4 as electrolyte. An all
      solid-state asymmetric supercapacitor (ASC) has been fabricated using Fe2 O3 and
      V2 O5 nanofibers as negative and positive electrodes, respectively. It could be
      operated at up to 1.8 V, taking advantage of the wide and opposite potential
      windows of the respective electrodes. The assembled all-solid-state ASC achieved
      a high energy density up to 32.2 W h kg-1 at an average power density of 128.7 W
      kg-1 , and exhibited excellent cycling stability and power capability. The
      effective and facile synthesis method and superior electrochemical performance
      described herein make electrospun Fe2 O3 and V2 O5 NFs promising electrode
      materials for high-performance ASCs.

PMID- 29660803
TI  - New 2D Carbon Nitride Organic Materials Synthesis with Huge-Application Prospects
      in CN Photocatalyst.
AB  - In recent years, 2D materials are attracting increased attention because of their
      excellent properties. In this paper, new 2D carbon nitride (CN) organic materials
      are successfully prepared on the basis of the organic synthesis theory, and the
      thickness is about 1.5 nm. This new 2D CN organic material further strengthens
      the 2D materials family. Meanwhile, their synthetic mechanism is theoretically
      speculated. Then CN photocatalysts of several structures are obtained by roasting
      2D CN organic materials. Through the photocatalytic hydrogen production
      experiments, the results exhibit that these kinds of photocatalysts have good
      photocatalytic effects compared to common g-C3 N4 .

PMID- 29660804
TI  - Nutritional stress reduces flight performance and exploratory behavior in a
      butterfly.
AB  - Anthropogenic global change, including agricultural intensification and climate
      change, poses a substantial challenge to many herbivores due to a reduced
      availability of feeding resources. The concomitant food stress is expected to
      detrimentally affect performance, amongst others in dispersal-related traits.
      Thus, while dispersal is of utmost importance to escape from deteriorating
      habitat conditions, such conditions may negatively feedback on the ability to do
      so. Therefore, we here investigate the impact of larval and adult food stress on
      traits related to dispersal ability, including morphology, physiology, flight
      performance, and exploratory behavior, in a butterfly. We show that inadequate
      nutrition during development and in the adult stage diminishes flight
      performance, despite some re-allocation of somatic resources. Detrimental effects
      of food stress on flight performance were mainly caused by reductions in body
      mass and storage reserves. Similar results were found for exploratory behavior.
      Furthermore, exploratory behavior was found to be (moderately) repeatable at the
      individual level, which might indicate the existence of a personality trait. This
      notion is further supported by the fact that flight performance and exploratory
      behavior were positively correlated, potentially suggesting the existence of a
      dispersal syndrome. In summary, our findings may have important implications for
      dispersal in natural environments, as the conditions requiring dispersal the most
      impair flight ability and thereby likely dispersal rates.

PMID- 29660805
TI  - Hierarchically Structured FeNiOx Hy Electrocatalyst Formed by In Situ
      Transformation of Metal Phosphate for Efficient Oxygen Evolution Reaction.
AB  - A simple and low-cost fabrication method is needed to obtain effective and robust
      heterogeneous catalysts for the oxygen evolution reaction (OER). In this study,
      an electrocatalyst FeNiOx Hy with a hierarchical structure is synthesized on
      nickel foam by a simple fabrication method through anion exchange from a metal
      phosphate to a metal hydroxide. The as-fabricated FeNiOx Hy electrode requires
      overpotentials of 206 and 234 mV to deliver current densities of 10 and 50 mA cm
      2 , respectively. The catalytic performance of FeNiOx Hy is superior to that of
      most previously reported FeNi-based catalysts, including NiFe layered double
      hydroxide. The catalyst also shows good long-term durability at a current density
      of 50 mA cm-2 over 50 h with no activity decay under 1 m KOH. By comparison to
      the directly electrodeposited FeNi hydroxide in morphology and electrochemical
      properties, the improved activity of the catalyst could be mainly attributed to
      an enhancement of its intrinsic activity, which was caused by the anion exchange
      of phosphate to (oxy)hydroxide. Further studies by cyclic voltammetry indicated a
      stronger interaction between Ni and Fe from the negative shift of the oxidation
      peak of Ni2+ /Ni3+ in comparison with reported FeNiOx Hy , which promoted the
      generation of active Ni3+ species more easily. This work may provide a new
      approach to the simple preparation of effective and robust OER catalysts by anion
      exchange.

PMID- 29660806
TI  - From a Helix to a Small Cycle: Metadynamics-Inspired alphavbeta6 Integrin
      Selective Ligands.
AB  - The RGD-recognizing alphavbeta6 integrin has only recently emerged as a major
      target for cancer diagnosis and therapy. Thus, the development of selective, low
      molecular-weight ligands of this receptor is still in great demand. Here, a
      metadynamics-driven design strategy allowed us to successfully convert a helical
      nonapeptide into a cyclic pentapeptide (6) showing remarkable potency and
      alphavbeta6 specificity. NMR and docking studies elucidated the reasons for the
      high affinity and selectivity of this compound, setting the ground for the
      rational design of new alphavbeta6-specific small peptides or even
      peptidomimetics. In vivo PET imaging studies demonstrated the potential use of 6
      for medical applications.

PMID- 29660807
TI  - A randomised clinical trial comparing the 'sniffing' and neutral position using
      channelled (KingVision(r) ) and non-channelled (C-MAC(r) ) videolaryngoscopes.
AB  - Head and neck position is one of the factors which can be associated with
      difficult videolaryngoscopy and tracheal intubation. This prospective randomised
      clinical trial compared 'sniffing' and neutral positions using a channelled
      (KingVision(r) ) and a non-channelled (C-MAC(r) D-blade) videolaryngoscope in 200
      adult patients randomly allocated into four groups (KingVision 'sniffing',
      KingVision neutral, C-MAC 'sniffing' and C-MAC neutral). The primary outcome was
      the ease of tracheal intubation using the modified intubation difficulty scale
      (mIDS) score. Laryngoscopy time, intubation time, laryngoscopic view using the
      percentage of glottic opening (POGO) score and success rate of tracheal
      intubation were secondary outcomes. The median (IQR [range]) modified difficulty
      scale scores for the four groups, respectively, were 0 (0-1 [0-3]), 0 (0-1 [0
      4]), 1 (0-1 [0-5]) and 0 (0-1 [0-3]; p = 0.384). There was no significant
      difference in laryngoscopy time (p = 0.020), intubation time (p = 0.272) and
      success rate (p = 0.968) between the groups. The percentage of glottic opening
      score was lower for C-MAC neutral group as compared with other three groups (p =
      0.01). There was no significant difference in the ease of intubation between the
      'sniffing' and the neutral position when using the KingVision and the C-MAC
      videolaryngoscopes. Therefore, either of the two positions could be used with
      these types of videolaryngoscopes, if deemed advantageous for the patient.

PMID- 29660808
TI  - Longitudinal Theory of Mind (ToM) Development From Preschool to Adolescence With
      and Without ToM Delay.
AB  - Longitudinal tracking of 107 three- to-thirteen-year-olds in a cross-sequential
      design showed a 6-step theory of mind (ToM) sequence identified by a few past
      cross-sectional studies validly depicted longitudinal ToM development from early
      to middle childhood for typically developing (TD) children and those with ToM
      delays owing to deafness or autism. Substantively, all groups showed ToM progress
      throughout middle childhood. Atypical development was more extended and began and
      ended at lower levels than for TD children. Yet most children in all groups
      progressed over the study's mean 1.5 years. Findings help resolve theoretical
      debates about ToM development for children with and without delay and gain
      strength and weight via their applicability to three disparate groups varying in
      ToM timing and sequencing.

PMID- 29660809
TI  - Prosopis nigra Mesocarp Fine Flour, A Source of Phytochemicals with Potential
      Effect on Enzymes Linked to Metabolic Syndrome, Oxidative Stress, and
      Inflammatory Process.
AB  - : This work is part of the search in native food matrices from arid regions of
      Argentina of interest to improve human health. Prosopis species are ethnic food
      resources in South America capable of growing in arid and semi-arid environments.
      This work was focused to determine the nutritional and phytochemical composition
      of Prosopis nigra fine flour and to evaluate its biological properties. Flour
      showed a high level of sucrose (30.35 g/100 g flour), fiber (6.34 g/100 g flour),
      polyphenols (0.45 g GAE/100 g flour), and minerals (potassium, calcium, and
      magnesium). Apigenin C glycosides and phenylpropanoid acids were identified in
      free and bound phenolic enriched extracts, respectively. Polyphenols (especially
      free polyphenols) were able to inhibit enzymes associated with the metabolic
      syndrome, including alpha-amylase (IC50 30.1 MUg GAE/mL), alpha-glucosidase (IC50
      22.5 MUg GAE/mL), while bound phenolics may control lipase activity (IC50 33.5
      MUg GAE/mL) and exhibit antioxidant activity by different action mechanisms (SC50
      between 16 and 93 MUg GAE/mL). Both extracts were more effective to inhibit
      cyclooxygenase-2 than phospholipase A2 and lipoxygenase, proinflammatory enzymes.
      Polyphenolic extracts did not show any mutagenic effect. Our studies add value to
      this non-conventional flour as a promising food resource that could be used as a
      functional food or functional ingredient in formulations to reduce the risk of
      the development of obesity. These studies revalue our native resources by
      promoting their conservation, their use and their propagation. PRACTICAL
      APPLICATION: Pods of P. nigra are traditional food resources in South America.
      The non-conventional flour obtained from them is a food that inhibits enzymes
      linked to carbohydrates metabolism and lipids metabolism, show antioxidant
      activity and anti-inflamatory activity, principally on COX-2. This natural
      product is a promising resource that could be used as a functional food or as
      functional ingredient in food formulations for reduce the risk of the development
      of obesity. Our studies are relevant to stimulate a sustainable management of
      this specie and for its development as potential new crops.

PMID- 29660810
TI  - Sensory Profile, Drivers of Liking, and Influence of Information on the
      Acceptance of Low-Calorie Synbiotic and Probiotic Chocolate Ice Cream.
AB  - : The objective of this study was to evaluate the sensory profile and the
      influence of the information on the acceptance of the symbiotic chocolate ice
      cream made with sucrose and different sweeteners (aspartame, sucralose, neotame,
      Stevia with 60%, 85%, 95%, and 97% of rebaudioside A) through analysis of
      variance (ANOVA), Tukey's test, and partial least of square (PLS) regression.
      Quantitative descriptive analysis (QDA) was carried out by 18 assessors, who
      evaluated the samples in relation to the raised descriptors. Additionally, two
      acceptance tests (blind/informed) were performed with 120 consumers. The samples
      sweetened with sucralose and rebaudioside 97% presented similar profile to the
      control sample, thus having a better potential to replace sucrose in chocolate
      ice cream. The acceptance test carried out with information had higher scores for
      the attributes appearance, aroma, flavor, texture, and overall impression. The
      correlation between data from the acceptance tests and QDA showed that the
      descriptors "low-energy" and "natural sweetener" claims interfered negatively in
      the drivers of liking of chocolate ice cream. Therefore, we can conclude that
      some characteristics unnoticed by consumers were highlighted after providing the
      information about the product's characteristics. PRACTICAL APPLICATION: This
      research is important and contributes to the manufacture and development of low
      calorie chocolate ice cream with functional properties, guiding, through suitable
      sensory and statistical tools, the application of stevia and other artificial
      sweeteners in products with reduction or total absence of sucrose and
      highlighting the impact of the labeling of these products on consumer perception.

PMID- 29660811
TI  - Natural Borneol Enhances Paclitaxel-Induced Apoptosis of ESCC Cells by
      Inactivation of the PI3K/AKT.
AB  - : Paclitaxel (PTX) has been used in a variety of malignancies for inhibiting
      tumor development and improving survival. However, its clinical application is
      limited due to poor solubility, drug resistance, and gastrointestinal reactions.
      Natural borneol (NB), as a promoter, could help to improve drug absorption.
      Therefore, the aims of the present study were to investigate the ability of NB to
      synergize with PTX to induce human esophageal squamous cell carcinoma (ESCC)
      cells apoptosis and the underlying mechanism of synergistic effects. In this
      study, our findings showed that NB could effectively synergize with PTX to
      inhibit the survival of ESCC cells by inducing apoptosis. The molecular mechanism
      by western blotting elucidated that combination treatment with PTX and NB
      significantly activated apoptotic pathway by triggering upregulation of cleaved
      caspase-3 expression and downregulation of survivin and P-AKT expression. These
      results demonstrated that NB could strongly potentiate PTX-induced apoptosis in
      ESCC cells through suppressing PI3K/AKT pathway. Thus, the combination therapy
      with NB and PTX might be a promising treatment strategy for human esophageal
      cancer. PRACTICAL APPLICATION: Esophageal cancer is one of the most common
      cancers in the world. It has brought about a major public health problem. Many
      natural agents have been employed in the synergized treatments of esophageal
      cancer. This study provides a comprehensive way to investigate the ability of
      borneol to synergize with paclitaxel to induce human esophageal squamous cell
      carcinoma cells apoptosis and the underlying mechanism of synergistic effects.
      The research showed that the combination treatment with some natural agents might
      be a promising treatment strategy for human esophageal cancer.

PMID- 29660812
TI  - Tremor severity in Parkinson's disease and cortical changes of areas controlling
      movement sequencing: A preliminary study.
AB  - There remains much to learn about the changes in cortical anatomy that are
      associated with tremor severity in Parkinson's disease (PD). For this reason, we
      used a combination of structural neuroimaging to measure cortical thickness and
      neurophysiological studies to analyze whether PD tremor was associated with
      cortex integrity. Magnetic resonance imaging and neurophysiological assessment
      were performed in 13 nondemented PD patients (9 women, 69.2%) with a clearly
      tremor-dominant phenotype. Cortical reconstruction and volumetric segmentation
      were performed with the Freesurfer image analysis software. Assessment of tremor
      was performed by means of high-density surface electromyography (hdEMG) and
      inertial measurement units (IMUs). Individual motor unit discharge patterns were
      identified from surface hdEMG and tremor metrics quantifying motor unit
      synchronization from IMUs. Increased motor unit synchronization (i.e., more
      severe tremor) was associated with cortical changes (i.e., atrophy) in wide
      spread cortical areas, including caudal middle frontal regions bilaterally
      (dorsal premotor cortices), left inferior parietal lobe (posterior parietal
      cortex), left lateral orbitofrontal cortex, cingulate cortex bilaterally, left
      posterior and transverse temporal cortex, and left occipital lobe, as well as
      reduced left middle temporal volume. Given that the majority of these areas are
      involved in controlling movement sequencing, our results support Albert's classic
      hypothesis that PD tremor may be the result of an involuntary activation of a
      program of motor behavior used in the genesis of rapid voluntary alternating
      movements.

PMID- 29660813
TI  - Impact of psychiatric illness on decreased survival in elderly patients with
      bladder cancer in the United States.
AB  - BACKGROUND: Treatments for muscle-invasive bladder cancer are multimodal,
      complex, and often carry significant risks of physical and psychological
      morbidity. The objectives of this study were to define the incidence and types of
      psychiatric illnesses diagnosed after treatment and to determine their impact on
      survival outcomes. METHODS: In total, 3709 patients who were diagnosed with
      clinical stage T2 through T4a bladder cancer from January 1, 2002, to December
      31, 2011, from the Surveillance, Epidemiology, and End Results-Medicare were
      analyzed. Multivariable analysis and Cox proportional-hazards models were used to
      determine the predictors associated with psychiatric diagnosis and impact on
      survival outcomes. RESULTS: Of 3709 patients, 1870 (50.4%) were diagnosed with
      posttreatment psychiatric disorders. Patients who underwent radical cystectomy
      were identified as being at significantly greater risk of having a posttreatment
      psychiatric illness compared with those who received radiotherapy and/or
      chemotherapy (hazard ratio [HR], 1.19; 95% confidence interval [CI], 1.07-1.31; P
      = .001). In adjusted analyses, diagnosis of a psychiatric disorder resulted in
      significantly worse overall survival (HR, 2.80; 95% CI, 2.47-3.17; P < .001) and
      cancer-specific survival (HR, 2.39; 95% CI, 2.05-2.78; P < .001). CONCLUSIONS:
      One-half of patients with muscle-invasive bladder cancer who underwent treatment
      were diagnosed with a psychiatric disorder, which resulted in worse survival
      outcomes compared with patients who did not have a posttreatment psychiatric
      diagnosis. This information can be used to inform interventions to educate
      patients with muscle-invasive bladder cancer regarding the impact of different
      treatments on mental health. Cancer 2018. (c) 2018 American Cancer Society.

PMID- 29660814
TI  - Effects of CD36 Genotype on Oral Perception of Oleic Acid Supplemented Safflower
      Oil Emulsions in Two Ethnic Groups: A Preliminary Study.
AB  - Previous studies demonstrate humans can detect fatty acids via specialized
      sensors on the tongue, such as the CD36 receptor. Genetic variation at the common
      single nucleotide polymorphism rs1761667 of CD36 has been shown to differentially
      impact the perception of fatty acids, but comparative data among different ethnic
      groups are lacking. In a small cohort of Caucasian and East Asian young adults,
      we investigated if: (1) participants could detect oleic acid (C18:1) added to
      safflower oil emulsions at a constant ratio of 3% (w/v); (2) supplementation of
      oleic acid to safflower oil emulsions enhanced perception of fattiness and
      creaminess; and (3) variation at rs1761667 influenced oleic acid detection and
      fat taste perception. In a 3-alternate forced choice test, 62% of participants
      detected 2.9 +/- 0.7 mM oleic acid (or 0.08% w/v) in a 2.8% safflower oil
      emulsion. Supplementation of oleic acid did not enhance fattiness and creaminess
      perception for the cohort as a whole, though East Asians carrying the GG genotype
      perceived more overall fattiness and creaminess than their AA genotype
      counterparts (P < 0.001). No differences were observed for the Caucasians. These
      preliminary findings indicate that free oleic acid can be detected in an oil-in
      water emulsion at concentrations found in commercial oils, but it does not
      increase fattiness or creaminess perception. Additionally, variation at rs1761667
      may have ethnic-specific effects on fat taste perception.

PMID- 29660815
TI  - Scaling down of a deworming programme among school-age children after a thirty
      year successful intervention in the Bolivian Chaco.
AB  - OBJECTIVE: Preventive chemotherapy is the WHO-recommended control method for soil
      transmitted helminthiases. In the Bolivian Chaco, 6-monthly single-dose
      mebendazole delivery to school-age children achieved a dramatic decrease in soil
      transmitted helminthiases prevalence between 1987 and 2013. Consequently, in
      September 2016, preventive chemotherapy delivery was interrupted in nine rural
      communities. In compliance with WHO recommendations, we intensified surveillance
      to monitor soil-transmitted helminthiases prevalence and detect potential changes
      that would require interventions. METHODS: We conducted two cross-sectional
      parasitology surveys 12 months apart (September 2016-2017) among school-age
      children living in the communities where preventive chemotherapy delivery had
      been halted. Study design, methods of sampling and sample analysis technique
      (direct microscopy, Kato-Katz technique) followed WHO recommendations, aiming to
      obtain data representative of the Bolivian Chaco ecological zone. RESULTS: We
      collected 426 samples in 2016 and 520 in 2017. Soil-transmitted helminthiasis
      prevalence was unremarkable: 0.7% (95% CI 0-1.5%) in 2016 and 0.8% (0-1.5%) in
      2017. Conversely, the prevalence of tapeworms (13% in 2016, 12% in 2017) and
      intestinal protozoan infections (81% in 2016 and 75% in 2017) continued to be
      high. CONCLUSIONS: Our findings support the role of preventive chemotherapy in
      reducing soil-transmitted helminthiases transmission, as otherwise poor hygienic
      and health conditions persist in the Bolivian Chaco. A national survey, involving
      areas from all the ecological zones of Bolivia, is now warranted.

PMID- 29660816
TI  - Bacterial Communities in Serpa Cheese by Culture Dependent Techniques, 16S rRNA
      Gene Sequencing and High-throughput Sequencing Analysis.
AB  - : Serpa cheese is one of the traditional regional Portuguese cheeses having the
      Protected Denomination of Origin (PDO) designation. This study investigated the
      bacterial community in the traditional Portuguese Serpa cheese. The
      microorganisms identified at the end of ripening (30 days) mainly were lactic
      acid bacteria (LAB). Lactobacillus paracasei/Lactobacillus casei was the main
      species in cheese from PDO registered industries, whereas in non-PDO registered
      industries Lactobacillus brevis was highlighted, among other LAB.
      Enterobacteriaceae species were detected at 20% to 40% of the total isolates. The
      results obtained by high-throughput sequencing analysis confirmed that LAB was
      the main microbial group, with Lactococcus genus contributing to approximately
      40% to 60% of the population, followed by Leuconostoc and Lactobacillus. The
      Enterobacteriaceae family was also important. The differences between bacterial
      communities from PDO and non-PDO registered industries suggest that the lack of
      regulation of the cheese-making practices may influence unfavorably. The new
      knowledge about bacterial diversity in Serpa cheese could be useful to set up new
      ripening conditions, which favor the development of desirable microorganisms.
      PRACTICAL APPLICATION: The control of the manufacturing process of traditional
      cheeses can be improved through the knowledge of the bacterial diversity that
      develops. Thus, the growth of desirable microorganisms can be promoted to
      homogenize the final product.

PMID- 29660817
TI  - Impact of the interruption of a large heart failure regional disease management
      programme on hospital admission rates: a population-based study.

PMID- 29660818
TI  - Investigation of metabolic properties and effects of 17beta-carboxamide
      glucocorticoids on human peripheral blood leukocytes.
AB  - The biological activity of three previously synthesized 17beta-carboxamide
      glucocorticoids (BG, BEG, and MPEA) was tested in vitro on mitogen stimulated and
      non-stimulated peripheral blood mononuclear cells (MNCs) and granulocytes from
      human healthy donors, and the results were compared to the conventional
      glucocorticoid dexamethasone. The tested 17beta-carboxamide glucocorticoids did
      not induce decreases in MNC viability and proliferation, while modulation of
      reactive oxygen species (ROS) synthesis in granulocytes was dependent on the cell
      donor. The obtained results indicate the possibility of avoidance of strong
      lymphocyte suppression, which is generally recognized during administration of
      conventional glucocorticoids. Furthermore, the metabolism of the tested
      derivatives was predicted in silico. The predicted metabolites were synthesized
      and the in silico results were confirmed by in vitro evaluation of the metabolism
      of BG, BEG, and MPEA in human serum and in cultures of peripheral blood MNCs. The
      results of the biological activity and metabolism evaluation and of previous in
      vivo evaluations of biological activity indicate the soft drug nature of BG, BEG,
      and MPEA. In order to be fully considered as soft glucocorticoids, further
      investigations on the toxicity and activity of the formed metabolites are
      required.

PMID- 29660819
TI  - Increase in CTGF mRNA expression by respiratory syncytial virus infection is
      abrogated by caffeine in lung epithelial cells.
AB  - Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory
      tract infection in early childhood. Underlying pathomechanisms of elevated
      pulmonary morbidity in later infancy are largely unknown. We found that RSV
      infected H441 cells showed increased mRNA expression of connective tissue growth
      factor (CTGF), a key factor in airway remodeling. Additional dexamethasone
      treatment led to further elevated mRNA levels, indicating additive effects.
      Caffeine treatment prevented RSV-mediated increase in CTGF mRNA. RSV may be
      involved in airway remodeling processes by increasing CTGF mRNA expression.
      Caffeine might abrogate these negative effects and thereby help to restore lung
      homeostasis.

PMID- 29660820
TI  - Human immunodeficiency virus in patients with tuberculous meningitis: systematic
      review and meta-analysis.
AB  - INTRODUCTION: Human immunodeficiency virus (HIV)-infected individuals are at
      increased risk for all forms of extrapulmonary tuberculosis (TB), including
      tuberculous meningitis (TBM). This study aimed to investigate the frequency of
      HIV in patients with TBM. METHODS: PubMed, Embase, Web of Science and Cochrane
      Library were searched for articles including relevant data. Stata version 14.0
      (StataCorp, College Station, Texas, USA) was used to analyse the data. RESULTS:
      Twenty studies were identified. The pooled frequency of HIV among adult patients
      with TBM was 38.0% (95% CI: 21.0-57.0; I2 = 97%). In children (under the age of
      15 years), 6.0% (95% CI: 1.0-13.0; I2 = 0.0%) had HIV infection. In patients with
      bacterial meningitis other than TBM, 36.0% (95% CI: 19.0-53.0; I2 = 100%) were
      HIV-infected. CONCLUSIONS: A relatively high frequency of HIV in patients with
      TBM was indicated by our study. Establishment of diagnostic criteria and
      effective treatment strategies for TBM/HIV co-infection are recommended for
      better management of patients with TBM+HIV.

PMID- 29660821
TI  - Like sheep, like humans? Right ventricular remodelling in a preterm-born ovine
      model.

PMID- 29660822
TI  - Managing work and cancer treatment: Experiences among survivors of hematological
      cancer.
AB  - BACKGROUND: The current study was performed to characterize the employment status
      of survivors of hematological cancer who have an informal caregiver from the time
      of diagnosis through the first 6 months of treatment. METHODS: Using a mixed
      methods approach, semistructured interviews with survivors of hematological
      cancer were conducted within 6 months of the initiation of cancer treatment.
      Interviews assessed cancer treatment status, barriers and facilitators to
      employment, financial and insurance status, and relationship with the primary
      caregiver. These results are part of a longitudinal study of cancer survivors and
      informal caregivers. RESULTS: A total of 171 patients were enrolled. Within 6
      months of beginning cancer treatments, approximately 35% were no longer employed.
      Reasons to remain employed included financial need, employee benefits, and a
      sense of purpose and normalcy. Employer accommodations and supportive colleagues
      facilitated continued employment. Logistic regression analysis demonstrated that
      having a higher household income, a desire to work, nonphysical job tasks, and
      congruent survivor-caregiver communication were associated with greater odds of
      remaining employed. CONCLUSIONS: Within 6 months of initiating cancer treatment,
      the majority of survivors of hematological cancer had maintained employment.
      Because of the limitations imposed by the physical stress of cancer treatments,
      as well as the need to maintain employment to continue receiving employee
      benefits to cover such treatments, survivors of hematological cancer likely would
      benefit from employment accommodations that are sensitive to their unique needs.
      Cancer 2018;124:2824-2831. (c) 2018 American Cancer Society.

PMID- 29660823
TI  - Radiographic morphology of intrabony defects in the first molars of patients with
      localized aggressive periodontitis: Comparison with health and chronic
      periodontitis.
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to describe the radiographic
      features of the first molars of patients with localized aggressive periodontitis
      (LAgP) and of their associated intrabony defects and to compare them with a
      control sample of chronic periodontitis cases and healthy subjects. METHODS: Data
      from a total of 93 patients were included in this analysis. First, dental
      panoramic tomograms of 34 patients with LAgP (131 first molars) and 30
      periodontally healthy patients (110 first molars) were compared. Then, periapical
      radiographs of the first molars of the same patients with LAgP and of 29 patients
      with chronic periodontitis affected by intrabony defects were analysed. RESULTS:
      Shorter root trunks were associated with the presence of intrabony defects in
      patients with LAgP (P = .002 at multilevel logistic regression), also when LAgP
      molars were compared with healthy subjects (P = .036). Although no difference in
      defect depth and angle was noted between LAgP and chronic periodontitis intrabony
      defects, LAgP intrabony defects appeared to be more frequently symmetrical and
      arch-shaped than in chronic periodontitis (P = .008), with positive predictive
      value and negative predictive value of for 'wide arch' defect of 87.3% (95% CI =
      77.2%-93.3%) and 32.3% (95% CI = 27.7%-37.2%) respectively. CONCLUSION: First
      molars of patients with LAgP affected by intrabony defects may have some distinct
      radiographic anatomical characteristics to those of healthy subjects. The shape
      of intrabony defects seems to differ between LAgP and chronic periodontitis
      cases. Further studies need to confirm these features and investigate if they are
      related to the initiation and progression of periodontitis.

PMID- 29660824
TI  - Histological Study of Ultrastructural Changes in Muscle Exposed to Various
      Concentrations of NaCl Brine.
AB  - : Efforts to reduce NaCl content in meat products hinge on gaining a deeper
      understanding of how NaCl content shapes product changes during the salting
      process. Bovine semitendinosus muscle samples were incubated for 5 days in 7
      different brine baths at NaCl concentrations of 0 (control), 0.15, 0.30, 0.50,
      0.75, 1.0, and 1.5 M, respectively. Histological and ultrastructural analyses
      showed that after incubation, muscle fiber size increased almost 30% in 0.15 and
      0.3 M NaCl brine but decreased in 0.50 and 0.75 M NaCl. At above 0.75 M NaCl,
      brining led to significantly degraded muscle tissue, preventing the morphological
      characterization by image analysis. Structural modifications were strongest in
      samples immersed in 1 M NaCl brine. M and Z lines showed dramatic solubilization
      from 0.5 M NaCl upwards. Extracted proteins were released into subsarcolemmal
      space at 0.75 M NaCl then into extracellular space at higher NaCl levels. These
      findings bring insight into the sequence of structural alterations in meat as a
      function of ionic strength, making it possible to optimize the meat salting
      process. PRACTICAL APPLICATION: Knowledge on the relationship between NaCl
      concentration, in situ structural changes and transfers of salt-extracted
      proteins can be usefully mobilized to reduce sodium content in cured meat
      products.

PMID- 29660825
TI  - Reply to: Frequency of squamous cell carcinoma in situ (SCCIS) and SCC in re
      excisions of biopsy-proven cutaneous SCCIS.

PMID- 29660826
TI  - Human coronaviruses and other respiratory infections in young adults on a
      university campus: Prevalence, symptoms, and shedding.
AB  - BACKGROUND: The prevalence, symptom course, and shedding in persons infected with
      the 4 most common human coronaviruses (HCoV)-229E, HKU1, NL63, and OC43 are
      poorly described. OBJECTIVES: We estimate their prevalence and associated
      symptoms among college students identified via a social network study design.
      PATIENTS/METHODS: We collected 1-3 samples (n = 250 specimens) from 176
      participants between October 2012 and January 17, 2013: participants with acute
      respiratory infection (ARI; cough and body aches or chills or fever/feverishness)
      and their social contacts. Virus was detected using RT-PCR. RESULTS: 30.4%
      (76/250) of specimens tested positive for any virus tested, and 4.8% (12/250)
      were positive for 2 or more viruses. Human coronaviruses (HCoVs [22.0%; 55/250]),
      rhinovirus (7.6%; 19/250), and influenza A (6.4%; 16/250) were most prevalent.
      Symptoms changed significantly over time among ARI participants with HCoV: the
      prevalence of cough and chills decreased over 6 days (P = .04, and P = .01,
      respectively), while runny nose increased over the same period (P = .02). HCoV
      NL63 was the most frequent virus detected 6 days following symptom onset (8.9%),
      followed by rhinovirus (6.7%). CONCLUSIONS: During a 3-month period covering a
      single season, HCoVs were common, even among social contacts without respiratory
      symptoms; specific symptoms may change over the course of HCoV-associated illness
      and were similar to symptoms from influenza and rhinovirus.

PMID- 29660827
TI  - Patient blood management and the importance of the Transfusion Practitioner role
      to embed this into practice.
AB  - Patient blood management (PBM) is a widely established international initiative,
      with a multidisciplinary approach to reduce transfusion. The Transfusion
      Practitioner1 (TP) role is well embedded in the United Kingdom (UK) and
      Australia. The value of the TP in changing both culture and practice to implement
      an all-inclusive PBM approach to care will be discussed. The TP role was born
      from both a safety and haemovigilance culture, where the greatest identified risk
      to the patient undergoing a transfusion was human error. From this initial
      trigger for improved safety, the TP role has evolved to a multifaceted, highly
      specialised role, involved in both PBM and transfusion processes. As the
      transfusion paradigm shifted from product to patient, the TP role evolved to
      include PBM, with an emphasis on the patients and the impact transfusion has on
      them. A multidisciplinary team is required to drive both PBM and transfusion; the
      TP is recognised as a critical link in the multidisciplinary team. They are seen
      as a driving force for change, bridging the gap between the laboratory and
      clinical arenas. The TP plays a vital role in helping establish and embed PBM
      that improves patient and safety outcomes.

PMID- 29660828
TI  - Storage Stability of Dietary Nitrate and Phenolic Compounds in Beetroot (Beta
      vulgaris) and Arugula (Eruca sativa) Juices.
AB  - : Nitrate and polyphenols from the diet may enhance the production and
      bioavailability of nitric oxide, a radical signaling molecule critical for
      cardiovascular health. Understanding the stability of these bioactives in
      beetroot and arugula juices is important for their functions. In this study, the
      stability of nitrate and phenolics in beetroot and arugula juices was measured
      for 32 days at different temperatures (25, 4, -20, and -80  degrees C). The
      levels of nitrate were measured by reversed-phase HPLC and initial levels were
      found to be 4965.34 +/- 72.69 MUg/mL for beetroot and 6310.20 +/- 24.79 MUg/mL
      for arugula. Interestingly, nitrate degradation started within 24 hr at 25 
      degrees C and after 4 days at 4  degrees C. At -20  degrees C and -80  degrees C,
      nitrate levels remained stable for one month. Total phenolics and free radical
      scavenging activity varied significantly during storage conditions. Beetroot
      juice at 25  degrees C, significant decrease in total phenolics and antioxidant
      activity was observed, whereas at 4, -20 and -80  degrees C, the levels remained
      relatively stable. By contrast, arugula juice at 25 and 4  degrees C, an increase
      in total phenolics and antioxidant activity were observed after one month.
      Furthermore, UPLC-HR-QTOF-MS analysis demonstrated that flavonoid glucosides were
      converted to their aglycones and lower phenolics, resulting in higher total
      phenolics and antioxidant activity during storage. In conclusion, beetroot and
      arugula juices required frozen conditions for long-term storage to prevent
      degradation of nitrate and to maintain their nutritional value. PRACTICAL
      APPLICATION: Beetroot and arugula juices have health-beneficial compounds such as
      nitrate and phenolics. Understanding the proper storage conditions can allow
      consumers to make informed choices that can help fresh juices to maintain their
      health promoting properties.

PMID- 29660829
TI  - Structural Modification of Fish Gelatin by the Addition of Gellan, kappa
      Carrageenan, and Salts Mimics the Critical Physicochemical Properties of Pork
      Gelatin.
AB  - : Pork gelatin is not suitable for halal and kosher application; however, fish
      gelatin (FG) can be modified for use as a pork gelatin (PG) mimetic. Herein, low
      acyl gellan (GE), kappa-carrageenan (KC), and salts (CaCl2 or KCl) were combined
      with a 180 Bloom tilapia FG. A formulation comprising 5.925% (w/v) FG + 0.025%
      (w/v) GE + 3mM CaCl2 best matched the physicochemical properties of PG. The
      modification increased the FG gel strength from 115 +/- 2 to 149 +/- 2 g
      (matching the 148 +/- 2 of PG), while the Tm increased from 27.9 +/- 1.0 to 32.4
      +/- 0.8  degrees C (matching the 33.1 +/- 0.3  degrees C of PG). Nanoaggregates
      (diameter between 150 and 300 nm) could be an important structural factor
      affecting the physicochemical properties, as both PG and GE-modified FG showed a
      similar frequency distribution in this size group (57.4 +/- 1.6% (PG) compared
      with 56.3 +/- 2.2% (modified FG)). To further explore the differences between KC
      and GE in modifying of FG's structure, the FG-KC and FG-GE gels were compared.
      The zeta potential and Fourier transform infrared (FTIR) spectroscopy results for
      the FG-KC gel supported an associative interaction with complex formation, as
      indicated from the large aggregates and amorphous phase under atomic force
      microscopy (AFM). Contrastingly, a segregative FG-GE interaction took place in
      presence of CaCl2 . These structures and interaction differences between FG-GE
      and FG-KC influenced the macro-properties of FG, possibly explaining the
      differences in the modification of the melting temperature of FG. A diagram
      representing the interaction-structure-physicochemical properties was proposed to
      explain the differences between the FG-GE and FG-KC gels. PRACTICAL APPLICATION:
      Certain people cannot consume any pork product or derivatives for religious
      reasons, thus it is essential to find a pork gelatin (PG) substitute for food
      product development. The commonly used polysaccharides, gellan and carrageenan,
      together with salt, can be added to fish gelatin (FG) to match the textural
      properties of PG, representing a promising substitute for PG. The difference in
      the mechanism of gellan and carrageenan to improve properties of FG has been
      revealed from nanostructure level. The use of food grade ingredients and simple
      mixing process are favorable in the food industry.

PMID- 29660830
TI  - Diagnosis of primary peritoneal high-grade serous carcinoma in a man by cytology.

PMID- 29660831
TI  - Managing microbiomes for human health: An annotated selection of World Wide Web
      sites relevant to the topics in microbial biotechnology.

PMID- 29660832
TI  - First-year GFR slope and long-term renal outcome in IgA nephropathy.
AB  - BACKGROUND: IgA nephropathy (IgAN) is the most frequent primary glomerular
      disease and the leading cause of end-stage renal disease. We investigated
      clinicopathologic predictors of renal survival in patients with IgAN with a focus
      on glomerular filtration rate (GFR) decline slope. MATERIALS AND METHODS: We
      screened all patients with primary IgAN between 1995 and 2012. Renal progression
      was defined as doubling of serum creatinine. Using serial serum creatinine levels
      during the first-year, we calculated the GFR decline slopes. Further, we defined
      patients in the steepest GFR slope quartile as rapid decliners and those in the
      second steepest GFR slope quartile as slow decliners. Others were defined as
      nondecliners. RESULTS: Of 214 participants, baseline GFR was 81 (62, 100)
      mL/min/1.73 m2 , which was not different among the 3 groups. Rapid decliners and
      slow decliners had higher levels of urinary protein/creatinine ratio (0.88, 0.89
      and 0.58 g/gCr, respectively, P < .001). Five-year renal survival was 76% in
      rapid decliners, 91% in slow decliners and 100% in nondecliners (P < .001, rapid
      or slow decliners vs nondecliners). After adjustment for clinicopathologic
      variables, slow decliners were associated with an 8.8-fold higher risk of
      progression (P = .011), and rapid decliners were associated with a 10.2-fold
      increased risk of progression (P = .007) compared with nondecliners. CONCLUSIONS:
      First-year GFR slope was associated with increased risk of renal progression,
      independent of proteinuria and histologic findings. Further studies are needed to
      investigate whether early GFR change can identify high-risk patients who benefit
      from immunosuppressive treatment in IgAN.

PMID- 29660833
TI  - Selenium deficiency and pregnancy outcome in pregnant women with HIV in Lagos,
      Nigeria.
AB  - OBJECTIVE: To investigate the prevalence of maternal selenium deficiency and its
      effects on pregnancy outcomes in pregnant women with HIV in Lagos, Nigeria.
      METHODS: The present descriptive cross-sectional study enrolled women aged 15-49
      years with HIV who were at 14-26 weeks of a singleton pregnancy and were
      attending Lagos University Teaching Hospital, Lagos, Nigeria, between August 1,
      2016, and April 30, 2017. Participants were selected by consecutive sampling and
      baseline data were collected through interviews. Venous blood samples were
      obtained to measure selenium concentrations, and associations between low
      maternal selenium concentrations (defined as <0.89 MUmol/L) and pregnancy
      outcomes were examined using bivariate and multivariate analysis. RESULTS: The
      final analysis included 113 patients; selenium deficiency was recorded in 23
      (20.4%) patients. Women with selenium deficiency had an approximately eight-fold
      higher risk of preterm delivery (adjusted odds ratio 7.61, 95% confidence
      interval 4.37-18.89; P=0.031) and of delivering a term neonate with a low
      delivery weight (adjusted odds ratio 8.11, 95% confidence interval 3.27-17.22;
      P=0.012), compared with women with a normal selenium concentration. CONCLUSION:
      The prevalence of selenium deficiency among pregnant women with HIV in Lagos was
      relatively high. The significant associations observed between maternal selenium
      deficiency and adverse pregnancy outcomes could have implications for the future
      management of HIV in pregnancy.

PMID- 29660834
TI  - The first case of ischemia-free organ transplantation in humans: A proof of
      concept.

PMID- 29660835
TI  - PDGFRA mRNA overexpression is associated with regional metastasis and reduced
      survival in oral squamous cell carcinoma.
AB  - BACKGROUND: Platelet-derived growth factor alpha (PDGFRA) is a gene encoding
      tyrosine kinase receptor and both EGFR and PDGFRA activate tyrosine kinases. The
      implication of PGFRA in many cancers and its prognostic significance irrespective
      to EGFR status in spinal chordoma, gliomas, and uterine cancers have shown a need
      for its investigation in oral squamous cell carcinoma (OSCC). We investigated the
      prognostic value of PDGFRA mRNA expression in OSCC. PATIENTS AND METHODS: The
      study was conducted in the department of oral maxillofacial surgery-head and neck
      oncology, at a tertiary hospital. The data on PDGFRA mRNA expression and
      immunohistochemical staining status in primary OSCC patients treated for curative
      surgery from 2010 to 2012 were analyzed. Univariate and multivariate analyses
      were performed with other cofactors for survival. RESULTS: A total of 114
      consecutive patients with primary OSCC who received treatment were studied.
      Thirty-one patients died of the disease. Strong PDGFRA immunohistochemical
      staining and high expression of PDGFRA mRNA were associated with positive pN
      status (P < .001), disease-free survival (P < .001), and overall survival (P <
      .001) in multivariate cox regression when all other factors such as pN status and
      histological grading were analyzed. Kaplan-Meier analysis revealed that the 2
      year survival and 3-year survival of patients with PDGFRA mRNA low expression
      were 96.83%. However, 2-year survival for PDGFRA mRNA high expression level was
      59.64%, which decreased to 45.57% by 3-years. CONCLUSION: PDGFRA overexpression
      in oral SCC, in respect to strong PDGFRA immunohistochemical staining and high
      PDGFRA mRNA expression, was positively associated with regional metastasis and
      reduced patient survival.

PMID- 29660836
TI  - Final results of a phase 2, open-label study of indisulam, idarubicin, and
      cytarabine in patients with relapsed or refractory acute myeloid leukemia and
      high-risk myelodysplastic syndrome.
AB  - BACKGROUND: Indisulam possesses anticancer properties through down-regulation of
      various cell-cycle checkpoint molecules, thereby blocking the phosphorylation of
      retinoblastoma protein and inducing p53 and p21. Indisulam exhibits synergy with
      nucleoside analogs and topoisomerase inhibitors. METHODS: The authors designed a
      phase 2 study of indisulam in combination with idarubicin and cytarabine in
      patients who had relapsed/refractory acute myeloid leukemia AML and high-risk
      myelodysplastic syndrome. In stage 1, patients received intravenous indisulam at
      400 mg/m2 on days 1 and 8 of a 28-day cycle. If they had no response, then
      patients received same dose schedule of indisulam followed by intravenous
      idarubicin 8 mg/m2 daily for 3 days and cytarabine 1.0 g/m2 over 24 hours daily
      on days 9 through 12 (for those aged < 60 years) or days 9 through 11 (for those
      aged > 60 years) of a 28-day cycle. Primary endpoints included the overall
      response rate, and secondary objectives included overall survival. RESULTS: Forty
      patients were enrolled. Of the 37 evaluable patients, 31 received indisulam with
      chemotherapy. Of these, 11 (35%) responded for a median duration of 5.3 months.
      The estimated 1-year overall survival rate was 51% for responders compared with 8
      % for nonresponders (P < .001). The most common grade >=3 nonhematologic
      toxicities were electrolyte abnormalities (50%) and febrile neutropenia (28%).
      CONCLUSIONS: The combination of indisulam with idarubicin and cytarabine yielded
      a 35% response rate in heavily pretreated patients with AML. With emerging data
      identifying the expression of DCAF15 (DDB1 and CUL4-associated factor 15) as a
      potential biomarker for activity, the combination of indisulam with idarubicin
      and cytarabine should be studied in a biomarker-driven trial or in patients who
      have splicing factor mutations. Cancer 2018;124:2758-65. (c) 2018 American Cancer
      Society. Cancer 2018;124:2758-2765. (c) 2018 American Cancer Society.

PMID- 29660837
TI  - DICER1 hot-spot mutations in ovarian gynandroblastoma.
AB  - AIMS: Gynandroblastoma is a rare ovarian sex cord-stromal tumour characterised by
      the presence of both male (Sertoli and/or Leydig cells) and female (granulosa
      cells) components. We investigated the mutational status of DICER1, FOXL2 and
      AKT1 genes at hot-spot regions that are known to be the key driving events in the
      development of Sertoli-Leydig cell tumour (SLCT), adult granulosa cell tumour
      (aGCT) and juvenile granulosa cell tumour (jGCT), respectively, to gain insights
      into the molecular pathogenesis of gynandroblastoma. METHODS AND RESULTS: Sixteen
      cases of gynandroblastoma were studied. All contained SLCT or Sertoli cell tumour
      components. aGCT and jGCT components were identified in seven and 10 cases,
      respectively, with one presenting both components. Heterozygous hot-spot
      mutations in the RNase IIIb domain of DICER1 were discovered in three cases,
      including one case with heterologous mucinous elements, all of which were
      composed of moderately or poorly differentiated SLCT and jGCT components, and
      harboured the mutations in both histological components. None of the 16 cases
      displayed mutations at the p.C134W (c.402C->G) of FOXL2 or within the pleckstrin
      homology domain of AKT1. All cases showed FOXL2 immunostaining in both male and
      female components. CONCLUSION: DICER1 hot-spot mutation is the key-driving event
      in a subset of gynandroblastomas containing components of SLCT and jGCT.
      Gynandroblastomas composed of SLCT and jGCT may represent morphological variants
      of SLCT. The molecular basis of gynandroblastoma containing a component of aGCT
      is different from pure aGCT.

PMID- 29660839
TI  - Highlights from the 2017 North American Cystic Fibrosis Conference.
AB  - The 31st annual North American Cystic Fibrosis Conference (NACFC) was held in
      Indianapolis, IN on November 2-4, 2017. Abstracts of presentations from the
      conference were published in a supplement to Pediatric Pulmonology [2017; Pediatr
      Pulmonol Suppl. 52: S1-S776]. The current review summarizes several major topic
      areas addressed at the conference: the pathophysiology and basic science of
      cystic fibrosis (CF) lung disease, clinical trials, clinical management issues,
      and quality improvement (QI). In this review, we describe emerging concepts in
      several areas of CF research and care.

PMID- 29660838
TI  - TDP-43 pathology in multiple system atrophy: colocalization of TDP-43 and alpha
      synuclein in glial cytoplasmic inclusions.
AB  - AIMS: This study aimed to assess clinicopathologic features of transactive
      response DNA-binding protein of 43 kDa (TDP-43) pathology and its risk factors in
      multiple system atrophy (MSA). METHODS: Paraffin-embedded sections of the
      amygdala and basal forebrain from 186 autopsy-confirmed MSA cases were screened
      with immunohistochemistry for phospho-TDP-43. In cases having TDP-43 pathology,
      additional brain regions were assessed. Immunohistochemical and
      immunofluorescence double-staining and immunogold electron microscopy (IEM) were
      performed to evaluate colocalization of TDP-43 and alpha-synuclein. Genetic risk
      factors for TDP-43 pathology were also analysed. RESULTS: Immunohistochemistry
      showed various morphologies of TDP-43 pathology in 13 cases (7%), such as subpial
      astrocytic inclusions, neuronal inclusions, dystrophic neurites, perivascular
      inclusions and glial cytoplasmic inclusions (GCIs). Multivariable logistic
      regression models revealed that only advanced age, but not concurrent Alzheimer's
      disease, argyrophilic grain disease or hippocampal sclerosis, was an independent
      risk factor for TDP-43 pathology in MSA (OR: 1.11, 95% CI: 1.04-1.19, P = 0.002).
      TDP-43 pathology was restricted to the amygdala in eight cases and extended to
      the hippocampus in two cases. The remaining three cases had widespread TDP-43
      pathology. Immunohistochemical and immunofluorescence double-staining and IEM
      revealed colocalization of alpha-synuclein and TDP-43 in GCIs with granule-coated
      filaments. Pilot genetic studies failed to show associations between risk
      variants of TMEM106B or GRN and TDP-43 pathology. CONCLUSIONS: TDP-43 pathology
      is rare in MSA and occurs mainly in the medial temporal lobe. Advanced age is a
      risk factor for TDP-43 pathology in MSA. Colocalization of TDP-43 and alpha
      synuclein in GCIs suggests possible direct interaction between the two molecules.

PMID- 29660840
TI  - The effectiveness of magnesium sulfate for status asthmaticus outside the
      intensive care setting.
AB  - AIM: Magnesium is an adjunctive therapy used in patients with status asthmaticus
      who do not respond to conventional therapy. The optimal time from initiation of
      therapy, to determination of response and administration of magnesium has not yet
      been resolved. Our objective was to determine if magnesium administered in the
      non-intensive care setting can decrease duration of continuous albuterol and
      hospital length of stay. METHODS: We performed a retrospective cohort analysis of
      children ages 2-18 years admitted to the pediatric unit on continuous albuterol
      between January 2014 and December 2015 in a tertiary care children's hospital.
      Cohorts were matched on respiratory assessment score (RAS) obtained at a similar
      duration of albuterol therapy and evaluated for the total duration of continuous
      albuterol, length of stay (LOS), and adverse events. RESULTS: Thirty-three
      patients who received magnesium were matched to 33 patients with the same RAS at
      a similar duration of continuous albuterol therapy who did not receive magnesium.
      Those who received magnesium had longer duration on continuous albuterol (34 vs
      18 h; P = 0.001; 95% confidence interval [CI] 4-20; effect size 0.41) and longer
      LOS (72 vs 49 h; P = 0.037; 95% confidence interval [CI] 1-33; effect size 0.26)
      than those who did not receive magnesium. CONCLUSION: Children requiring
      continuous albuterol for status asthmaticus can be administered magnesium sulfate
      outside the PICU with a low incidence of adverse events; however, among a RAS
      matched cohort, those who received magnesium did not experience shorter time on
      continuous albuterol, or hospital length of stay.

PMID- 29660841
TI  - Design of Trifluoroalkenyl Iodonium Salts for a Hypervalency-Aided Alkenylation
      Cyclization Strategy: Metal-Free Construction of Aziridine Rings.
AB  - The synthesis of fluorinated compounds and their use as pharmaceutical
      ingredients or synthetic building blocks have been in the focus of chemical and
      medicinal research. However, the efficient synthesis of trifluoromethylated
      nitrogen heterocycles is sometimes challenging. Herein, we disclose a simple
      aziridination process that relies on the use of amines and novel alkenyl iodonium
      reagents for the synthesis of strained, trifluoromethylated heterocycles. With
      the utilization of a newly designed and bench-stable but highly reactive
      hypervalent alkenyl iodonium species, these three-membered-ring heterocyclic
      compounds can be efficiently constructed from simple amines under mild conditions
      in the absence of transition-metal catalysts. The special reactivity of the new
      trifluoropropenyl synthon towards nucleophilic centers could be exploited in more
      general cyclization and alkenylation reactions in the future.

PMID- 29660842
TI  - Kinetic models of hematopoietic differentiation.
AB  - As cell and molecular biology is becoming increasingly quantitative, there is an
      upsurge of interest in mechanistic modeling at different levels of resolution.
      Such models mostly concern kinetics and include gene and protein interactions as
      well as cell population dynamics. The final goal of these models is to provide
      experimental predictions, which is now taking on. However, even without matured
      predictions, kinetic models serve the purpose of compressing a plurality of
      experimental results into something that can empower the data interpretation, and
      importantly, suggesting new experiments by turning "knobs" in silico. Once
      formulated, kinetic models can be executed in terms of molecular rate equations
      for concentrations or by stochastic simulations when only a limited number of
      copies are involved. Developmental processes, in particular those of stem and
      progenitor cell commitments, are not only topical but also particularly suitable
      for kinetic modeling due to the finite number of key genes involved in cellular
      decisions. Stem and progenitor cell commitment processes have been subject to
      intense experimental studies over the last decade with some emphasis on embryonic
      and hematopoietic stem cells. Gene and protein interactions governing these
      processes can be modeled by binary Boolean rules or by continuous-valued models
      with interactions set by binding strengths. Conceptual insights along with tested
      predictions have emerged from such kinetic models. Here we review kinetic
      modeling efforts applied to stem cell developmental systems with focus on
      hematopoiesis. We highlight the future challenges including multi-scale models
      integrating cell dynamical and transcriptional models. This article is
      categorized under: Models of Systems Properties and Processes > Mechanistic
      Models Developmental Biology > Stem Cell Biology and Regeneration.

PMID- 29660843
TI  - Mortality after a cerebrovascular event in age-related macular degeneration
      patients treated with bevacizumab ocular injections.
AB  - PURPOSE: To analyse the mortality associated with intravitreal injections of
      bevacizumab for age-related macular degeneration (AMD) in patients previously
      diagnosed with stroke or transient ischaemic attack (TIA). METHODS: We reviewed
      bevacizumab-treated AMD patients with a diagnosis of stroke or TIA prior to their
      first bevacizumab injection (n = 948). Those patients, naive to any anti-vascular
      endothelial growth factor (anti-VEGF) at the time of stroke/TIA, were then
      compared to age- and gender-matched patients who had a stroke/TIA at the same
      time and had never been exposed to anti-VEGF. Survival analysis was performed
      using adjusted Cox regression. The main outcome measure was survival. Adjusted
      variables were age, smoking, alcohol abuse, hypertension, diabetes mellitus,
      obesity, ischaemic heart disease, congestive heart failure and liver cancer.
      RESULTS: Age and gender distribution of bevacizumab-treated patients and controls
      were similar (mean age: 83.4 versus 83.7 years, p = 0.3; 51.7% males versus 52.5%
      males, p = 0.7). The adjusted mortality in patients who received bevacizumab
      within 3 months after stroke/TIA was significantly different than in patients non
      exposed to bevacizumab (OR = 6.92, 95%, CI 1.88-25.43, p < 0.01). Within 6 months
      after stroke/TIA, the difference in adjusted mortality showed a strong trend (OR
      = 2.00, 95%, CI 0.96-4.16, p = 0.064). Within 12 months, it was insignificant (OR
      = 1.30, 95%, CI 0.75-2.26, p = 0.348). CONCLUSION: We found increased mortality
      within three months after a cerebrovascular event in patients treated with
      bevacizumab for AMD compared to patients for whom there was no record of a
      prescription to any anti-VEGF agent.

PMID- 29660844
TI  - Moray micro forceps biopsy improves the diagnosis of specific pancreatic cysts.
AB  - BACKGROUND: Making a specific diagnosis of pancreatic cysts preoperatively is
      difficult. The new disposable Moray micro forceps biopsy (MFB) device allows
      tissue sampling from the pancreatic cyst wall/septum and aims to improve
      diagnosis. This study compares the diagnostic performance of the MFB with the
      current conventional analysis of pancreatic cyst fluid (PCF). METHODS: A total of
      48 patients sampled with MFB were identified. Cysts were classified as mucinous
      on PCF based on extracellular mucin/mucinous epithelium, carcinoembryonic antigen
      (CEA) levels >=192 ng/mL, or KRAS/GNAS mutation. A diagnosis of intraductal
      papillary mucinous neoplasm was supported by GNAS mutation; a diagnosis of serous
      cystadenoma was supported by Von Hippel-Lindau tumor suppressor (VHL) mutation. A
      diagnosis of mucinous cystic neoplasm required the presence of subepithelial
      ovarian-type stroma. A high-risk cyst was defined as a mucinous cyst with high
      grade dysplasia or an adenocarcinoma. Comparisons in diagnostic performance
      between PCF and MFB were made. RESULTS: The mean age of the patients was 69.6
      years (range, 27-90 years); 25 of 48 patients (52.1%) were female. Cysts were in
      the pancreatic head (13 patients), neck (2 patients), body (20 patients), and
      tail (13 patients), averaging 3.1 cm (range, 1.2-6.0 cm). There was concordance
      with mucinous versus nonmucinous classification (60.4% for PCF vs 58.3% for MFB;
      P = .949). Three high-risk cysts were detected by PCF and 2 were detected by MFB
      (P = .670). However, MFB diagnosed significantly more specific cysts compared
      with PCF (50.0% for MFB vs 18.8% for PCF; P<.001). CONCLUSIONS: PCF analysis and
      MFB have comparable performance in distinguishing between mucinous and
      nonmucinous cysts and for detecting high-risk cysts. However, MFB was found to be
      superior for diagnosing specific cyst subtypes, thus adding significant value to
      preoperative patient management. Cancer Cytopathol 2018;126:414-20. (c) 2018
      American Cancer Society.

PMID- 29660845
TI  - Effects of Different Acyl Gellan Gums on the Rheological Properties and Colloidal
      Stability of Blueberry Cloudy Juice.
AB  - : In this study, gellan gums with different acyl contents were prepared, and
      their effects on blueberry cloudy juices were compared. The rheological
      properties, stability coefficients, sedimentations, color parameters and particle
      size distributions of blueberry cloudy juices with 0.035% (w/w) of gellan gum
      were measured. As the acyl content increased, the viscosity increased, and the
      sedimentation and stability coefficient values decreased. Gellan gums with higher
      acyl contents provided better beverage stabilizing capabilities through stricter
      enforcement of the molecular associations. Overall, this study provides valuable
      information for enhancing the gelation and stabilization of blueberry cloudy
      juices, confirms the superiority of high acyl gellan gums for inhibiting the
      color fading of anthocyanins, and further guides the development of novel product
      concepts. PRACTICAL APPLICATION: Cloudy juices made from blueberries have many
      benefits. However, the particles in cloudy juices will flocculate during storage,
      resulting in an undesirable precipitate. In our work, gellan gums with different
      acyl contents were prepared and applied to blueberry juice to prevent
      aggregation. The results provide valuable information for enhancing the
      stabilization of blueberry juices, confirm the superiority of high acyl gellan
      for inhibiting color fading, and further guide the development of novel product
      concepts.

PMID- 29660846
TI  - Phospholipase D2 promotes disease progression of renal cell carcinoma through the
      induction of angiogenin.
AB  - A hallmark of clear cell renal cell carcinoma (ccRCC) is the presence of
      intracellular lipid droplets (LD) and it is assumed that phosphatidic acid (PA)
      produced by phospholipase D (PLD) plays some role in the LD formation. However,
      little is known about the significance of PLD in ccRCC. In this study, we
      examined the expression levels of PLD in ccRCC. The classical mammalian isoforms
      of PLD are PLD1 and PLD2, and the levels of both mRNA were higher at the primary
      tumor sites than in normal kidney tissues. Similarly, both PLD were significantly
      abundant in tumor cells as determined by analysis using immunohistochemical
      staining. Importantly, a higher level of PLD was significantly associated with a
      higher tumor stage and grade. Because PLD2 knockdown effectively suppressed the
      cell proliferation and invasion of ccRCC as compared with PLD1 in vitro, we
      examined the effect of PLD2 in vivo. Notably, shRNA-mediated knockdown of PLD2
      suppressed the growth and invasion of tumors in nude mouse xenograft models.
      Moreover, the higher expression of PLD2 was significantly associated with poorer
      prognosis in 67 patients. As for genes relating to the tumor invasion of PLD2, we
      found that angiogenin (ANG) was positively regulated by PLD2. In fact, the
      expression levels of ANG were elevated in tumor tissues as compared with normal
      kidney and the inhibition of ANG activity with a neutralizing antibody
      significantly suppressed tumor invasion. Overall, we revealed for the first time
      that PLD2-produced PA promoted cell invasion through the expression of ANG in
      ccRCC cells.

PMID- 29660847
TI  - Glu571 of PheT plays a pivotal role in the thermal stability of Escherichia coli
      PheRS enzyme.
AB  - As of date the two temperature sensitive mutations isolated in pheST operon
      include pheS5 (G293 ->A293 ) and pheT354. Recently, we reported that G673 of pheS
      defines a hot spot for intragenic suppressors of pheS5. In this investigation, in
      13 independent experiments, a collection of temperature sensitive mutants were
      isolated by localized mutagenesis. Complementation using clones bearing pheS+ ,
      pheT+ , and pheS+ T+ indicated that 34 mutants could harbor lesion(s) in pheS and
      four could be in pheT and one mutant might be a double mutant. Surprisingly, all
      the 34 pheS mutants harbored the very same (G293 ->A293 ) transition mutation as
      present in the classical pheS5 mutant. Most unexpectedly, the four pheT mutants
      isolated harbored the same G1711 ->A1711 transition, a mutation which is hitherto
      unreported. Since all the four pheT mutants were defined by the same G1711 
      >A1711 base change, we believe that getting other mutations could be hard hitting
      and therefore it is proposed that G1711 itself could be a "hot spot" for
      emergence of Ts mutations in pheT and similarly G293 itself could be a "hot spot"
      for Ts lesions in pheS. These results clearly imply a vital role for Glutamic
      acid571 (Glu571 ) of PheT and reinforce criticality of Glycine98 (Gly98 ) of PheS
      in the thermal stability of PheRS enzyme.

PMID- 29660850
TI  - Regioselective C-H Xanthylation as a Platform for Polyolefin Functionalization.
AB  - Polyolefins that contain polar functional groups are important materials for next
      generation lightweight engineering thermoplastics. Post-polymerization
      modification is an ideal method for the incorporation of polar groups into
      branched polyolefins; however, it typically results in chain scission events,
      which have deleterious effects on polymer properties. Herein, we report a metal
      free method for radical-mediated C-H xanthylation that results in the
      regioselective functionalization of branched polyolefins without coincident
      polymer-chain scission. This method enables a tunable degree of polymer
      functionalization and capitalizes on the versatility of the xanthate functional
      group to unlock a wide variety of C-H transformations previously inaccessible on
      branched polyolefins.

PMID- 29660849
TI  - Comparison of human papillomavirus genotyping and cytology triage, COMPACT Study:
      Design, methods and baseline results in 14 642 women.
AB  - Although cytology-based screening programs have significantly reduced mortality
      and morbidity from cervical cancer, the global consensus is that primary human
      papillomavirus (HPV) testing for cervical screening increases detection of high
      grade cervical intraepithelial neoplasia (CIN) and invasive cancer. However, the
      optimal triage strategy for HPV-positive women to avoid over-referral to
      colposcopy may be setting specific. As Japan requires data that have been
      generated domestically to modify screening guidelines, we conducted a 3-year
      prospective study, COMparison of HPV genotyping And Cytology Triage (COMPACT), to
      evaluate the potential role of HPV16/18 partial genotyping and cytology for
      primary HPV screening. In total, 14 642 women aged 20 to 69 years undergoing
      routine screening at 3 centers in Hokkaido were enrolled. Conventional cytology
      and HPV testing were carried out. Women with abnormal cytology or HPV16/18
      positivity underwent colposcopy. Those with 12 other high-risk (hr) HPV types
      underwent repeat cytology after 6 months. Primary study endpoints were detection
      of high-grade cervical disease defined as CIN2/CIN3 or greater as determined by
      consensus pathology. Prevalence of cytological abnormalities was 2.4%. hrHPV, HPV
      16, and HPV 18 were detected in 4.6%, 0.9%, and 0.3% of women, respectively.
      HPV16/18 were detected in all (8/8) invasive cervical cancers and in all (2/2)
      adenocarcinomas in situ. Both cytological abnormalities and hrHPV positivity
      declined with increasing age. This is the first Japanese study to investigate the
      role of partial genotyping and cytology in an HPV-based screening program.
      Results should help policy-makers develop guidelines for future cervical
      screening programs and management of cervical abnormalities based on HPV
      genotype.

PMID- 29660851
TI  - Temporal trends in management and outcomes of testicular cancer: A population
      based study.
AB  - BACKGROUND: Treatment guidelines for early-stage testicular cancer have
      increasingly recommended de-escalation of therapy with surveillance strategies.
      This study was designed to describe temporal trends in routine clinical practice
      and to determine whether de-escalation of therapy is associated with inferior
      survival in the general population. METHODS: The Ontario Cancer Registry was
      linked to electronic records of treatment to identify all patients diagnosed with
      testicular cancer treated with orchiectomy in Ontario during 2000-2010. Treatment
      after orchiectomy was classified as radiotherapy (RT), retroperitoneal lymph node
      dissection (RPLND), chemotherapy, or none. Surveillance was defined as no
      identified treatment within 90 days of orchiectomy. Overall survival (OS) and
      cancer-specific survival (CSS) were measured from the date of orchiectomy.
      RESULTS: The study population included 1564 and 1086 cases of seminomas and
      nonseminoma germ cell tumors (NSGCTs), respectively. Among patients with
      seminomas, there was a significant increase in the proportion of patients with no
      treatment within 90 days of orchiectomy (from 56% to 84%; P < .001); the use of
      RT decreased over time (from 38% to 8%; P < .001); and the use of chemotherapy
      remained stable (from 6% to 9%; P = .289). Practice patterns 90 days after
      orchiectomy remained stable over time among patients with NSGCTs: from 51% to 57%
      for no treatment (P = .435), from 43% to 43% for chemotherapy (P = .336), and
      from 9% to 3% for RPLND (P = .476). The OS rates for the entire cohort at 5 and
      10 years were 97% and 96%, respectively; the CSS rates were 98% and 98%,
      respectively. There was no significant change in OS or CSS for patients with
      seminomas or NSGCTs during the study period. CONCLUSIONS: There has been
      substantial de-escalation in the treatment of testicular cancer in routine
      practice since 2000. Long-term survival in routine practice is excellent and has
      not decreased with the uptake of surveillance strategies. Cancer 2018;124:2724
      2732. (c) 2018 American Cancer Society.

PMID- 29660852
TI  - Etiology and functional validation of gastrointestinal motility dysfunction in a
      zebrafish model of CHARGE syndrome.
AB  - CHARGE syndrome is linked to autosomal-dominant mutations in the CHD7 gene and
      results in a number of physiological and structural abnormalities, including
      heart defects, hearing and vision loss, and gastrointestinal (GI) problems. Of
      these challenges, GI problems have a profound impact throughout an individual's
      life, resulting in increased morbidity and mortality. A homolog of CHD7 has been
      identified in the zebrafish, the loss of which recapitulates many of the features
      of the human disease. Using a morpholino chd7 knockdown model complemented by a
      chd7 null mutant zebrafish line, we examined GI structure, innervation, and
      motility in larval zebrafish. Loss of chd7 resulted in physically smaller GI
      tracts with normal epithelial and muscular histology, but decreased and
      disorganized vagal projections, particularly in the foregut. chd7 morphant larvae
      had significantly less ability to empty their GI tract of gavaged fluorescent
      beads, and this condition was only minimally improved by the prokinetic agents,
      domperidone and erythromycin, in keeping with mixed responses to these agents in
      patients with CHARGE syndrome. The conserved genetics and transparency of the
      zebrafish have provided new insights into the consequences of chd7 gene
      dysfunction on the GI system and cranial nerve patterning. These findings
      highlight the opportunity of the zebrafish to serve as a preclinical model for
      studying compounds that may improve GI motility in individuals with CHARGE
      syndrome.

PMID- 29660848
TI  - International collaborative study to assess cardiovascular risk and evaluate long
      term health in cats with preclinical hypertrophic cardiomyopathy and apparently
      healthy cats: The REVEAL Study.
AB  - BACKGROUND: Hypertrophic cardiomyopathy is the most prevalent heart disorder in
      cats and principal cause of cardiovascular morbidity and mortality. Yet, the
      impact of preclinical disease is unresolved. HYPOTHESIS/OBJECTIVES: Observational
      study to characterize cardiovascular morbidity and survival in cats with
      preclinical nonobstructive (HCM) and obstructive (HOCM) hypertrophic
      cardiomyopathy and in apparently healthy cats (AH). ANIMALS: One thousand seven
      hundred and thirty client-owned cats (430 preclinical HCM; 578 preclinical HOCM;
      722 AH). METHODS: Retrospective multicenter, longitudinal, cohort study. Cats
      from 21 countries were followed through medical record review and owner or
      referring veterinarian interviews. Data were analyzed to compare long-term
      outcomes, incidence, and risk for congestive heart failure (CHF), arterial
      thromboembolism (ATE), and cardiovascular death. RESULTS: During the study
      period, CHF, ATE, or both occurred in 30.5% and cardiovascular death in 27.9% of
      1008 HCM/HOCM cats. Risk assessed at 1, 5, and 10 years after study entry was
      7.0%/3.5%, 19.9%/9.7%, and 23.9%/11.3% for CHF/ATE, and 6.7%, 22.8%, and 28.3%
      for cardiovascular death, respectively. There were no statistically significant
      differences between HOCM compared with HCM for cardiovascular morbidity or
      mortality, time from diagnosis to development of morbidity, or cardiovascular
      survival. Cats that developed cardiovascular morbidity had short survival (mean
      +/- standard deviation, 1.3 +/- 1.7 years). Overall, prolonged longevity was
      recorded in a minority of preclinical HCM/HOCM cats with 10% reaching 9-15 years.
      CONCLUSIONS AND CLINICAL IMPORTANCE: Preclinical HCM/HOCM is a global health
      problem of cats that carries substantial risk for CHF, ATE, and cardiovascular
      death. This finding underscores the need to identify therapies and monitoring
      strategies that decrease morbidity and mortality.

PMID- 29660853
TI  - Shelf Life Extension of Tomato Paste Through Organoleptically Acceptable
      Concentration of Betel Leaf Essential Oil Under Accelerated Storage Environment.
AB  - : This study was attempted with two objectives: (1) to find an acceptable
      concentration of betel leaf essential oil (BLEO) based on sensory evaluation that
      can be employed in tomato paste; (2) to evaluate the effect of the acceptable
      concentration of BLEO in the paste during accelerated storage under 89 +/- 1.2%
      RH at 39 +/- 1  degrees C. Linguistic data obtained from sensory evaluation of
      tomato paste treated with 4 different concentrations of BLEO were analyzed using
      fuzzy logic approach. The organoleptically acceptable concentration was
      determined to be 0.25 mg/g of BLEO in tomato paste. The effect of the selected
      concentration of BLEO on different physicochemical and microbial attributes of
      tomato paste during accelerated storage was studied. Untreated tomato paste was
      found to have 12% less total antioxidant capacity than treated paste at the end
      of storage. Based on a* /b* value in CIELAB color space, the BLEO treated paste
      efficiently extended the shelf life by 14 days with respect to untreated paste
      samples under accelerated storage conditions. BLEO comes with a tag contributing
      to green consumerism, and its application as food preservative is no less than a
      value addition to the product. PRACTICAL APPLICATIONS: Essential oil is
      considered to have promising potential as an alternative food preservative, and
      its use is practically possible if they could overcome the sensory barrier, while
      retaining the preservative potency. The importance of identifying the sensory
      attributes for commercial success of essential oil treated food product was
      considered in this study. It contributes to the potency of organoleptically
      acceptable concentration of BLEO in shelf life extension of tomato paste under
      accelerated storage conditions. At industrial level, the estimated shelf life of
      treated tomato paste can be increased by incorporating more hurdles alongside
      BLEO.

PMID- 29660854
TI  - The Butanol Producing Microbe Clostridium beijerinckii NCIMB 14988 Manipulated
      Using Forward and Reverse Genetic Tools.
AB  - The solventogenic anaerobe Clostridium beijerinckii has potential for use in the
      sustainable bioconversion of plant-derived carbohydrates into solvents, such as
      butanol or acetone. However, relatively few strains have been extensively
      characterised either at the genomic level or through exemplification of a
      complete genetic toolkit. To remedy this situation, a new strain of C.
      beijerinckii, NCIMB 14988, is selected from among a total of 55 new clostridial
      isolates capable of growth on hexose and pentose sugars. Chosen on the basis of
      its favorable properties, the complete genome sequence of NCIMB 14988 is
      determined and a high-efficiency plasmid transformation protocol devised. The
      developed DNA transfer procedure allowed demonstration in NCIMB 14988 of the
      forward and reverse genetic techniques of transposon mutagenesis and gene
      knockout, respectively. The latter is accomplished through the successful
      deployment of both group II intron retargeting (ClosTron) and allelic exchange.
      In addition to gene inactivation, the developed allelic exchange procedure is
      used to create point mutations in the chromosome, allowing for the effect of
      amino acid changes in enzymes involved in primary metabolism to be characterized.
      ClosTron mediated disruption of the currently unannotated non-coding region
      between genes LF65_05915 and LF65_05920 is found to result in a non-sporulating
      phenotype.

PMID- 29660855
TI  - The impact of oral food challenges for food allergy on quality of life: A
      systematic review.
AB  - BACKGROUND: Food allergy significantly impairs health-related quality of life
      (HRQL). Currently, it is still unknown whether diagnostic interventions for food
      allergy improve HRQL. We aim to assess the impact of diagnostic interventions for
      food allergy on HRQL. METHODS: A systematic search was performed in MEDLINE,
      Embase, Cochrane Library, and CINAHL focused on patients with a (suspected) food
      allergy who underwent diagnostic interventions (ie, skin prick test, specific
      IgE, or oral food challenges [OFC]) and in whom HRQL was assessed. The mean
      difference between HRQL before and after the diagnostic intervention was
      calculated. A minimal clinically important difference of 0.5 was considered
      clinically relevant for the food allergy quality of life questionnaire. RESULTS:
      Seven of 1465 original identified publications were included in which the impact
      of an OFC on HRQL was investigated (total patients n = 1370). No other diagnostic
      interventions were investigated. Food allergy-specific parent-reported HRQL
      improved significantly after an OFC irrespective of the outcome in children with
      a suspected food allergy in two publications. The change was considered
      clinically relevant in one of two publications. In addition, parent-reported HRQL
      improved after an OFC to assess the eliciting dose in children with a confirmed
      food allergy. The parental burden was significantly reduced after an OFC to
      assess resolution of food allergy. A meta-analysis could not be performed due to
      the limited numbers of, and considerable heterogeneity between, eligible
      publications. CONCLUSION: An OFC is associated with an improved food allergy
      specific HRQL and a reduced parental burden of food allergy.

PMID- 29660856
TI  - Palladium-Catalyzed Insertion of Isocyanides into the C-S Bonds of Heteroaryl
      Sulfides.
AB  - Insertion of tert-butyl isocyanide into the C(sp2 )-S bonds of heteroaryl
      sulfides is catalyzed by a palladium diphosphine complex. Thioimidates generated
      through this reaction could be readily hydrolyzed under acidic conditions to
      yield the corresponding thioesters, which are of synthetic use. This insertion is
      useful because starting heteroaryl sulfides were readily prepared by either
      conventional ways or through sulfur-specific extended Pummerer reactions.

PMID- 29660857
TI  - Impact of Different Perfusion Modalities on Coronary and Carotid Blood Flow
      Velocities in an Adult ECLS Swine Model.
AB  - The objective of this study was to compare the effects of nonpulsatile and ECG
      synchronized pulsatile extracorporeal life support on coronary and carotid blood
      flow velocities using transthoracic echocardiography and vascular ultrasound,
      respectively. Nine adult swine were randomly separated into nonpulsatile (NP, n =
      5) and pulsatile (P, N = 4) groups and placed on ECLS for 24 h using an i-cor
      ECLS system. Noninvasive transthoracic images of the left and right coronary
      artery and the left carotid artery were acquired at the pre-ECLS (baseline), 30
      min, 3, 6, 9, 12, and 24 h on-ECLS stages. The mean diastolic velocity of the
      left and right coronary arteries in the NP group significantly decreased after 24
      h on ECLS compared to the baseline and 30 min ECLS stages (P < 0.05). There was
      no statistical difference in the mean diastolic velocity of the coronary arteries
      in the P group at 30 min, 3-, 6-, 9-, 12-, and 24-h ECLS compared to baseline.
      The P group showed a smaller decrease in the mean diastolic velocity of coronary
      arteries between the 30-min ECLS and 3-, 6-, 9-, 13-, 24-h ECLS stages compared
      to the NP group. The diastolic velocity of the left carotid artery in the NP
      group significantly decreased during 24-h ECLS compared to the P group (P <
      0.05). An ECG-synchronized pulsatile ECLS system appeared to maintain coronary
      and carotid artery diastolic velocities better than conventional nonpulsatile
      ECLS. Further investigation of the perfusion modes during ECLS is warranted.

PMID- 29660858
TI  - Peer counselling improves breastfeeding practices: A cluster randomized
      controlled trial in urban Bangladesh.
AB  - This study aimed to evaluate the impact of peer counselling on early initiation
      of breastfeeding (EIBF) and exclusive breastfeeding (EBF) rates for mother-infant
      pairs living in urban slums, Dhaka, Bangladesh. This randomized controlled trial
      enrolled 350 mother-infant pairs from selected slums between September 2014 and
      July 2016. The women assigned to intervention group received peer counselling
      from locally recruited, trained community female volunteers starting in third
      trimester of pregnancy until 6 months after delivery; control group received no
      intervention. EIBF, any liquids given after birth, and EBF were compared between
      groups. Follow-up was scheduled at enrolment, following childbirth, and every 2
      months up to 6 months after delivery. Multiple logistic regressions were used to
      assess the effect peer counselling and other associated factors on EIBF and EBF
      practices. EIBF rate was higher in the intervention group than in the control
      group (89.1% vs. 77.4%, p = .005). More mothers in intervention group were
      exclusively breastfeeding at 5 months than mothers in the control group (73% vs.
      27%, p < .005). Control mothers were twice as likely to not practice EIBF
      compared with intervention mothers (adjusted odds risk [aOR]: 2.53, CI [1.29,
      4.97], p = .007). Overall, caesarean section was associated with an 8.9-fold
      higher risk of not achieving EIBF (aOR: 8.90, CI [4.05, 19.55], p < .001).
      Intervention mothers were 5.10-fold more likely to practice EBF compared with
      control mothers (aOR: 5.10, CI [2.89, 9.01], p < .001) at 5 months. This study
      demonstrates peer counselling can positively influence both EIBF and EBF among
      mothers living in urban area.

PMID- 29660859
TI  - Permafrost thaw and climate warming may decrease the CO2, carbon, and metal
      concentration in peat soil waters of the Western Siberia Lowland.
AB  - Soil pore waters are a vital component of the ecosystem as they are efficient
      tracers of mineral weathering, plant litter leaching, and nutrient uptake by
      vegetation. In the permafrost environment, maximal hydraulic connectivity and
      element transport from soils to rivers and lakes occurs via supra-permafrost flow
      (i.e. water, gases, suspended matter, and solutes migration over the permafrost
      table). To assess possible consequences of permafrost thaw and climate warming on
      carbon and Green House gases (GHG) dynamics we used a "substituting space for
      time" approach in the largest frozen peatland of the world. We sampled stagnant
      supra-permafrost (active layer) waters in peat columns of western Siberia Lowland
      (WSL) across substantial gradients of climate (-4.0 to -9.1 degrees C mean annual
      temperature, 360 to 600mm annual precipitation), active layer thickness (ALT)
      (>300 to 40cm), and permafrost coverage (sporadic, discontinuous and continuous).
      We analyzed CO2, CH4, dissolved carbon, and major and trace elements (TE) in 93
      soil pit samples corresponding to several typical micro landscapes constituting
      the WSL territory (peat mounds, hollows, and permafrost subsidences and
      depressions). We expected a decrease in intensity of DOC and TE mobilization from
      soil and vegetation litter to the supra-permafrost water with increasing
      permafrost coverage, decreasing annual temperature and ALT along a latitudinal
      transect from 62.3 degrees N to 67.4 degrees N. However, a number of solutes
      (DOC, CO2, alkaline earth metals, Si, trivalent and tetravalent hydrolysates, and
      micronutrients (Mn, Co, Ni, Cu, V, Mo) exhibited a northward increasing trend
      with highest concentrations within the continuous permafrost zone. Within the
      "substituting space for time" climate change scenario and northward shift of the
      permafrost boundary, our results suggest that CO2, DOC, and many major and trace
      elements will decrease their concentration in soil supra-permafrost waters at the
      boundary between thaw and frozen layers. As a result, export of DOC and elements
      from peat soil to lakes and rivers of the WSL (and further to the Arctic Ocean)
      may decrease.

PMID- 29660860
TI  - Managing India's small landholder farms for food security and achieving the "4
      per Thousand" target.
AB  - The "4 per Thousand" initiative was launched at the 21st Conference of Parties
      (COP21) in December 2015 to address global climate change through the
      aspirational goal of increasing soil organic carbon (SOC) stock of the world to
      40-cm depth by an average annual rate of 4%. Small landholders (SLHs), often
      faced with difficult bio-physical and socio-economic conditions, are the
      principal managers of soil in India. There are 117 million SLHs representing 85%
      of the total operational holdings, cultivating over 72 million ha of land, and
      meeting 50-60% of India's food requirement. The agricultural soils of SLHs are
      strongly depleted of SOC and nutrient reserves. Therefore, the challenge of
      feeding 1.7 billion people in India by 2050 will depend on increasing the current
      productivity levels by restoring the depleted soils of SLHs. According to our
      estimates, soils of SLHs currently contain 1370-1770 Tg C and, which can be
      increased to 2460-2650 Tg C by 2050 through large-scale adoption of best
      management practices (BMPs) including balanced application of nutrients, compost,
      agroforestry, and conservation agriculture. A wide spread adoption of these
      practices can enhance C sequestration by 70-130 Tg CO2e per annum and produce 410
      440 million Mg of food grains accounting for 80-85% of the total requirement by
      2050. In this paper we propose strategies for achieving the dual objectives of
      advancing food security, the "4 per Thousand" target and mitigating climate
      change in India.

PMID- 29660861
TI  - The accumulation, transformation, and effects of quinestrol in duckweed
      (Spirodela polyrhiza L.).
AB  - Potential risk of endocrine disrupting compounds on non-target organisms has
      received extensive attentions in recent years. The present work aimed to
      investigate the behavior and effect of a synthetic steroid estrogen quinestrol in
      duckweed Spirodela polyrhiza L. Experimental results showed that quinestrol could
      be uptaken, accumulated, and biotransformed into 17 alpha-ethynylestradiol in S.
      polyrhiza L. The accumulation of quinestrol had a positive relation to the
      exposure concentration. The bioaccumulation rate was higher when the duckweed was
      exposed to quinestrol solutions at low concentrations than at high concentration.
      While the transformation of quinestrol showed no concentration-dependent manner.
      Quinestrol reduced the biomass and pigment content and increased superoxide
      dismutase and catalase activities and malondialdehyde contents in the duckweed.
      The results demonstrated that quinestrol could be accumulated and biotransformed
      in aquatic plant S. polyrhiza L. This work would provide supplemental data on the
      behavior of this steroid estrogen compound in aquatic system.

PMID- 29660862
TI  - Modeling fine particle dynamics in gravel-bedded streams: Storage and re
      suspension of fine particles.
AB  - Fine particles or sediments have various effects on water quality and aquatic
      ecosystems. Thus, understanding the dynamics of these fine particles between
      water body and stream bed is an important issue in sediment research. Previous
      studies and analysis of empirical data suggest that fine particles are stored in
      the sediment bed in the low flow regime, where flow rate is smaller than the
      critical flow rate that mobilizes the sediment bed. These fine particles are re
      suspended during flood events when the flow rate becomes larger than the critical
      flow rate that mobilizes bed material. The transition from pattern recognition to
      process analysis required incorporation of the dominant processes controlling
      fine particle dynamics within gravel-bedded streams into a model. The process
      analysis was performed using continuous flow and turbidity data at two locations
      on the Russian River in California to test process descriptions and then
      calibrate a quantitative model to represent those processes. The resulting
      process model coupled fine particle retention within the sediment bed by
      filtration and sedimentation with the release of accumulated fine particles in
      response to flood events. Model parameters, such as the critical flow rate
      required for initiating sediment bed fluidization, the maximum fine particle
      storage capacity within the sediment bed, and background particle concentration
      for the watershed, were estimated from the monitoring data. Model calibration
      optimized the filtration and the sediment bed fluidization parameters over two or
      three years of data. Overall, the difference between modeled and observed fine
      particle mass released from the sediment bed was within 20% of the measured mass.

PMID- 29660863
TI  - Petroleum produced water disposal: Mobility and transport of barium in sandstone
      and dolomite rocks.
AB  - To assess the risk of underground sources of drinking water contamination by
      barium (Ba) present in petroleum produced water disposed into deep saline
      aquifers, we examined the effect of salinity (NaCl), competition of cations (Ca,
      Mg), temperature (22 and 60 degrees C), and organic fracturing additives (guar
      gum) on the sorption and transport of Ba in dolomites and sandstones. We found
      that at typical concentration levels of NaCl, Ca, and Mg in petroleum produced
      water, Ba sorption in both dolomites and sandstones is inhibited by the formation
      of Ba(Cl)+ complexes in solution and/or the competition of cations for binding
      sites of minerals. The inhibition of Ba sorption by both mechanisms is greater in
      dolomites than in sandstones. This is reflected by a larger decrease in the
      breakthrough times of Ba through dolomites than through sandstones. We found that
      the presence of guar gum has little influence on the sorption and thus the
      transport of Ba in both dolomites and sandstones. Contrary to most heavy metals,
      Ba sorption in both dolomites and sandstones decreases with increasing
      temperature, however the reducing effect of temperature on Ba sorption is
      relevant only at low salinity conditions. Higher inhibition of Ba sorption in
      dolomites than in sandstones is due to the greater reactivity of dolomite over
      sandstone. The results of this study which includes the formulation of a reactive
      transport model and estimation of partition coefficients of Ba in dolomites and
      sandstones have significant implications in understanding and predicting the
      mobility and transport of Ba in deep dolomite and sandstone saline aquifers.

PMID- 29660864
TI  - Eyes in the sea: Unlocking the mysteries of the ocean using industrial, remotely
      operated vehicles (ROVs).
AB  - For thousands of years humankind has sought to explore our oceans. Evidence of
      this early intrigue dates back to 130,000BCE, but the advent of remotely operated
      vehicles (ROVs) in the 1950s introduced technology that has had significant
      impact on ocean exploration. Today, ROVs play a critical role in both military
      (e.g. retrieving torpedoes and mines) and salvage operations (e.g. locating
      historic shipwrecks such as the RMS Titanic), and are crucial for oil and gas
      (O&G) exploration and operations. Industrial ROVs collect millions of
      observations of our oceans each year, fueling scientific discoveries. Herein, we
      assembled a group of international ROV experts from both academia and industry to
      reflect on these discoveries and, more importantly, to identify key questions
      relating to our oceans that can be supported using industry ROVs. From a long
      list, we narrowed down to the 10 most important questions in ocean science that
      we feel can be supported (whole or in part) by increasing access to industry
      ROVs, and collaborations with the companies that use them. The questions covered
      opportunity (e.g. what is the resource value of the oceans?) to the impacts of
      global change (e.g. which marine ecosystems are most sensitive to anthropogenic
      impact?). Looking ahead, we provide recommendations for how data collected by
      ROVs can be maximised by higher levels of collaboration between academia and
      industry, resulting in win-win outcomes. What is clear from this work is that the
      potential of industrial ROV technology in unravelling the mysteries of our oceans
      is only just beginning to be realised. This is particularly important as the
      oceans are subject to increasing impacts from global change and industrial
      exploitation. The coming decades will represent an important time for scientists
      to partner with industry that use ROVs in order to make the most of these 'eyes
      in the sea'.

PMID- 29660865
TI  - Effect of genotype and crop year on the nutritional value of walnut virgin oil
      and defatted flour.
AB  - The present study analyses the health-promoting compounds of walnut oil and
      walnut defatted flour obtained using hydraulic pressing. To identify the cultivar
      effect, nine walnut varieties were harvested in the same plot for two years to
      control environmental and agricultural management effects on kernel chemical
      traits. Beyond the variability reported in the products obtained from the
      different cultivars analysed, the crop year showed a crucial effect in the
      nutritional value of walnut products. Specifically, the variability caused for
      the crop year in the concentration of oleic and linoleic acids, phytosterols,
      polyphenols, tocopherols, proteins and essential minerals (K, Mg, P, S, Cu, Fe,
      Mn, Mo, Ni) was greater that the reported for the genotype. These findings
      suggest that the nutritional value of walnut oil and walnut flour depends on the
      crop season largely than expected, even when average annual weather conditions
      are similar. As a result, focus must change in the study of cultivar effect on
      walnut products to a wider analysis of specific variables related to crop year
      conditions.

PMID- 29660866
TI  - Remediation of oil-contaminated harbor sediments by chemical oxidation.
AB  - Oil hydrocarbons are widespread pollutants in sub-surface sediments with serious
      threats to terrestrial and aquatic environment. However, very limited data is
      available about remediation of historically contaminated sediments. This study
      reports the use of magnetite-catalyzed chemical oxidation (H2O2 and Na2S2O8) to
      degrade oil hydrocarbons in aged contaminated sediments. For this purpose, oil
      contaminated sediments were sampled from three different locations in France
      including two harbors and one petroleum industrial channel. These sediments were
      characterized by different hydrocarbon index (HI) values (3.7-9.0gkg-1), total
      organic carbon contents (1.9%-8.4%) and textures (sand, slit loam and silt).
      Chemical oxidation was performed in batch system for one week at circumneutral pH
      by: H2O2 alone, H2O2/Fe(II), H2O2/magnetite, Na2S2O8 alone, Na2S2O8/Fe(II), and
      Na2S2O8/magnetite. Results obtained by GC-FID indicated substantial hydrocarbon
      degradation (40-70%) by H2O2/magnetite and Na2S2O8/magnetite. However, oxidants
      alone or with soluble Fe(II) caused small degradation (<5%). In the presence of
      H2O2/magnetite, degradation of extractable organic matter and that of HI were
      highly correlated. However, no such correlation was observed for
      Na2S2O8/magnetite which resulted in higher removal of HI indicating its selective
      oxidation behavior. Treatment efficiency was negatively influenced by organic
      carbon and carbonate contents. For being the first study to report chemical
      oxidation of oil hydrocarbons in real contaminated sediments, it may have
      practical implications to design a remediation strategy for target contaminants.

PMID- 29660867
TI  - Grassland futures in Great Britain - Productivity assessment and scenarios for
      land use change opportunities.
AB  - To optimise trade-offs provided by future changes in grassland use intensity,
      spatially and temporally explicit estimates of respective grassland
      productivities are required at the systems level. Here, we benchmark the
      potential national availability of grassland biomass, identify optimal strategies
      for its management, and investigate the relative importance of intensification
      over reversion (prioritising productivity versus environmental ecosystem
      services). Process-conservative meta-models for different grasslands were used to
      calculate the baseline dry matter yields (DMY; 1961-1990) at 1km2 resolution for
      the whole UK. The effects of climate change, rising atmospheric [CO2] and
      technological progress on baseline DMYs were used to estimate future grassland
      productivities (up to 2050) for low and medium CO2 emission scenarios of UKCP09.
      UK benchmark productivities of 12.5, 8.7 and 2.8t/ha on temporary, permanent and
      rough-grazing grassland, respectively, accounted for productivity gains by 2010.
      By 2050, productivities under medium emission scenario are predicted to increase
      to 15.5 and 9.8t/ha on temporary and permanent grassland, respectively, but not
      on rough grassland. Based on surveyed grassland distributions for Great Britain
      in 2010 the annual availability of grassland biomass is likely to rise from 64 to
      72milliontonnes by 2050. Assuming optimal N application could close existing
      productivity gaps of ca. 40% a range of management options could deliver
      additional 21*106tonnes of biomass available for bioenergy. Scenarios of changes
      in grassland use intensity demonstrated considerable scope for maintaining or
      further increasing grassland production and sparing some grassland for the
      provision of environmental ecosystem services.

PMID- 29660868
TI  - A new structure of permeable pavement for mitigating urban heat island.
AB  - The urban heat island (UHI) effect has been a great threat to human habitation,
      and how to mitigate this problem has been a global concern over decades. This
      paper addresses the cooling effect of a novel permeable pavement called
      evaporation-enhancing permeable pavement, which has capillary columns in
      aggregate and a liner at the bottom. To explore the efficiency of mitigating the
      UHI, bench-scale permeable pavement units with capillary columns were developed
      and compared with conventional permeable pavement. Criteria of capillary
      capacities of the column, evaporation rates, and surface temperature of the
      pavements were monitored under simulated rainfall and Shanghai local weather
      conditions. Results show the capillary column was important in increasing
      evaporation by lifting water from the bottom to the surface, and the evaporation
      enhancing permeable pavement was cooler than a conventional permeable pavement by
      as much as 9.4 degrees C during the experimental period. Moreover, the cooling
      effect of the former pavement could persist more than seven days under the
      condition of no further rainfall. Statistical analysis result reveals that
      evaporation-enhancing permeable pavement can mitigate the UHI effect
      significantly more than a conventional permeable pavement.

PMID- 29660869
TI  - Dysregulation of major functional genes in frontal cortex by maternal exposure to
      carbon black nanoparticle is not ameliorated by ascorbic acid pretreatment.
AB  - Recent cohort studies have revealed that perinatal exposure to particulate air
      pollution, including carbon-based nanoparticles, increases the risk of brain
      disorders. Although developmental neurotoxicity is currently a major issue in the
      toxicology of nanoparticles, critical information for understanding the
      mechanisms underlying the developmental neurotoxicity of airway exposure to
      carbon black nanoparticle (CB-NP) is still lacking. In order to investigate these
      mechanisms, we comprehensively analyzed fluctuations in the gene expression
      profile of the frontal cortex of offspring mice exposed maternally to CB-NP,
      using microarray analysis combined with Gene Ontology information. We also
      analyzed differences in the enriched function of genes dysregulated by maternal
      CB-NP exposure with and without ascorbic acid pretreatment to refine specific
      alterations in gene expression induced by CB-NP. Total of 652 and 775 genes were
      dysregulated by CB-NP in the frontal cortex of 6- and 12-week-old offspring mice,
      respectively. Among the genes dysregulated by CB-NP, those related to
      extracellular matrix structural constituent, cellular response to interferon
      beta, muscle organ development, and cysteine-type endopeptidase inhibitor
      activity were ameliorated by ascorbic acid pretreatment. A large proportion of
      the dysregulated genes, categorized in hemostasis, growth factor, chemotaxis,
      cell proliferation, blood vessel, and dopaminergic neurotransmission, were,
      however, not ameliorated by ascorbic acid pretreatment. The lack of effects of
      ascorbic acid on the dysregulation of genes following maternal CB-NP exposure
      suggests that the contribution of oxidative stress to the effects of CB-NP on
      these biological functions, i.e., cell migration and proliferation, blood vessel
      maintenance, and dopaminergic neuron system, may be limited. At least, ascorbic
      acid pretreatment is hardly likely to be able to protect the brain of offspring
      from developmental neurotoxicity of CB-NP. The present study provides insight
      into the mechanisms underlying developmental neurotoxicity following maternal
      nanoparticle exposure.

PMID- 29660871
TI  - Quantitative models for predicting adsorption of oxytetracycline, ciprofloxacin
      and sulfamerazine to swine manures with contrasting properties.
AB  - Understanding antibiotic adsorption in livestock manures is crucial to assess the
      fate and risk of antibiotics in the environment. In this study, three
      quantitative models developed with swine manure-water distribution coefficients
      (LgKd) for oxytetracycline (OTC), ciprofloxacin (CIP) and sulfamerazine (SM1) in
      swine manures. Physicochemical parameters (n=12) of the swine manure were used as
      independent variables using partial least-squares (PLSs) analysis. The cumulative
      cross-validated regression coefficients (Q2cum) values, standard deviations (SDs)
      and external validation coefficient (Q2ext) ranged from 0.761 to 0.868, 0.027 to
      0.064, and 0.743 to 0.827 for the three models; as such, internal and external
      predictability of the models were strong. The pH, soluble organic carbon (SOC)
      and nitrogen (SON), and Ca were important explanatory variables for the OTC
      Model, pH, SOC, and SON for the CIP-model, and pH, total organic nitrogen (TON),
      and SOC for the SM1-model. The high VIPs (variable importance in the projections)
      of pH (1.178-1.396), SOC (0.968-1.034), and SON (0.822 and 0.865) established
      these physicochemical parameters as likely being dominant (associatively) in
      affecting transport of antibiotics in swine manures.

PMID- 29660870
TI  - Differential behavioural responses to venlafaxine exposure route, warming and
      acidification in juvenile fish (Argyrosomus regius).
AB  - Antidepressants, such as venlafaxine (VFX), which are considered emerging
      environmental pollutants, are increasingly more present in the marine
      environment, and recent evidence suggest that they might have adverse effects on
      fish behaviour. Furthermore, altered environmental conditions associated to
      climate change (e.g. warming and acidification) can also have a determinant role
      on fish behaviour, fitness and survival. Yet, the underlying interactions between
      these environmental stressors (pharmaceuticals exposure and climate change) are
      still far from being fully understood. The aim of this study was to assess
      behavioural responses (in juvenile meagre (Argyrosomus regius) exposed to VFX via
      water ([VFX] ~20MUgL-1) and via dietary sources ([VFX] ~160MUgkg-1 dry weight),
      as well as to increased temperature (DeltaT degrees C=+5 degrees C) and high CO2
      levels (DeltapCO2 ~1000MUatm; equivalent to DeltapH=-0.4units). Overall, VFX
      bioaccumulation in fish plasma was enhanced under the combination of warming and
      acidification. VFX triggered fish exploration, whereas fish activity and shoal
      cohesion were reduced. Acidification alone decreased fish exploration and shoal
      cohesion, and reversed fish preference to turn leftwards compared to control
      conditions. Such alterations were further enhanced by VFX exposure. The
      combination of warming and acidification also reduced shoal cohesion and loss of
      lateralization, regardless of VFX exposure. The distinct behaviour observed when
      VFX contamination, acidification and warming acted alone or in combination
      highlighted the need to consider the likely interactive effects of seawater
      warming and acidification in future research regarding the toxicological aspects
      of chemical contaminants.

PMID- 29660872
TI  - Understanding the relationships between grazing intensity and the distribution of
      nitrifying communities in grassland soils.
AB  - Nitrifying microbes are of critical importance in regulating efficient nitrogen
      (N) cycling, which plays a crucial role in plant productivity and maintaining
      soil sustainability. Long-term different intensities of grazing can strongly
      influence the microbial communities, while our understanding of the complex
      nitrifying community in the grazed grassland soil environment is still limited.
      To investigate whether and how long-term grazing with different intensities
      influence soil nitrifying communities, high-throughput sequencing and
      quantitative PCR analyses were performed on soil samples from permanent grassland
      soils under four grazing intensities: 0 (G0), 1.5 (G1), 6 (G2) and 9 (G3) sheepha
      1. Results showed that the G3 treatment significantly reduced the soil nutrient
      content and increased the soil bulk density, changes that are not sustainable in
      the long run. The G1 treatment, on the other hand, significantly increased the
      soil nutrient content and would improve soil fertility. Some functional microbes
      were specifically enriched after long term grazing, like Nitrospirae (phylum) to
      Nitrospira (class) in the G2 samples and Chromatiales (order) to Nitrosococcus
      (genus) in the G3 soils. The numerically dominant Nitrosococcus watsonii lineage
      of ammonia oxidizing bacteria (AOB) was observed in this grassland soil. The
      redundancy analysis (RDA) together with the structural equation modeling (SEM)
      analysis showed that grazing intensity was important in mediating the
      distribution of soil microorganisms and affected nitrifying communities by
      impacting soil physicochemical characteristics (e.g., bulk density, NH4+-N).
      These results showed the shifts of nitrifying communities across different
      grazing intensities, and could aid in the determination of an optimal grazing
      intensity for these grazed grassland soils.

PMID- 29660873
TI  - Determining the speciation of Zn in soils around the sediment ponds of chemical
      plants by XRD and XAFS spectroscopy and sequential extraction.
AB  - For a correct assessment of risk of polluted soil, it is crucial to establish the
      speciation and mobility of the contaminants. The aim of this study was to
      investigate the speciation and transformation of Zn in strongly technogenically
      transformed contaminated Spolic Technosols for a long time in territory of sludge
      collectors by combining analytical techniques and synchrotron techniques.
      Sequential fractionation of Zn compounds in studied soils revealed increasing
      metal mobility. Phyllosilicates and Fe and Mn hydroxides were the main
      stabilizers of Zn mobility. A high degree of transformation was identified for
      the composition of the mineral phase in Spolic Technosols by X-ray powder
      diffraction. Technogenic phases (Zn-containing authigenic minerals) were revealed
      in Spolic Technosols samples through the analysis of their Zn K-edge EXAFS and
      XANES spectra. In one of the samples Zn local environment was formed by
      predominantly oxygen atoms, and in the other one mixed ZnS and ZnO bonding was
      found. Zn speciation in the studied technogenically transformed soils was due to
      the composition of pollutants contaminating the floodplain landscapes for a long
      time, and, second, this is the combination of physicochemical properties
      controlling the buffer properties of investigated soils. X-ray spectroscopic and
      X-ray powder diffraction analyses combined with sequential extraction assays is
      an effective tool to check the affinity of the soil components for heavy metal
      cations.

PMID- 29660874
TI  - Biogas recovery from two-phase anaerobic digestion of food waste and paper waste:
      Optimization of paper waste addition.
AB  - In order to optimize the biogas recovery from the co-digestion of food waste (FW)
      and paper waste (PW), the effect of PW content on two-phase anaerobic digestion
      (TPAD) was investigated. The mixtures of FW and PW, with the ratios of 10:0, 8:2,
      6:4 and 5:5 (total solids), were fed into TPAD to recover biomethane. After the
      long-term expriment, it is elucidated that the methanogenesis in TPAD was stable
      for PW <= 40%. When PW = 50%, NH4HCO3 was added to the methanogenic phase to
      provide nitrogen. As the indicators of the stability of the anaerobic process,
      the ammonia and alkalinity in the methanogenic phase were simulated for their
      decreasing trend. The simulation results quantified the nitrogen deficiency in
      the methanogenic phase for PW = 50%. Also, the comparison of alkalinity and
      ammonia revealed that ammonia was the major contributor to the alkalinity.
      Furthermore, via stoichiometric calculations, high C/N ratios were found to
      increase the microbial yield and exacerbated the nitrogen deficiency. In the
      energy estimation, adding PW showed significant increase only when PW >= 40%. It
      was concluded that 40% was the optimal PW content for bioenergy augmentation from
      co-digestion of FW and PW using TPAD.

PMID- 29660875
TI  - Metagenomic analysis of antibiotic resistance genes (ARGs) during refuse
      decomposition.
AB  - Landfill is important reservoirs of residual antibiotics and antibiotic
      resistance genes (ARGs), but the mechanism of landfill application influence on
      antibiotic resistance remains unclear. Although refuse decomposition plays a
      crucial role in landfill stabilization, its impact on the antibiotic resistance
      has not been well characterized. To better understand the impact, we studied the
      dynamics of ARGs and the bacterial community composition during refuse
      decomposition in a bench-scale bioreactor after long term operation (265d) based
      on metagenomics analysis. The total abundances of ARGs increased from 431.0ppm in
      the initial aerobic phase (AP) to 643.9ppm in the later methanogenic phase (MP)
      during refuse decomposition, suggesting that application of landfill for
      municipal solid waste (MSW) treatment may elevate the level of ARGs. A shift from
      drug-specific (bacitracin, tetracycline and sulfonamide) resistance to multidrug
      resistance was observed during the refuse decomposition and was driven by a shift
      of potential bacteria hosts. The elevated abundance of Pseudomonas mainly
      contributed to the increasing abundance of multidrug ARGs (mexF and mexW).
      Accordingly, the percentage of ARGs encoding an efflux pump increased during
      refuse decomposition, suggesting that potential bacteria hosts developed this
      mechanism to adapt to the carbon and energy shortage when biodegradable
      substances were depleted. Overall, our findings indicate that the use of landfill
      for MSW treatment increased antibiotic resistance, and demonstrate the need for a
      comprehensive investigation of antibiotic resistance in landfill.

PMID- 29660876
TI  - Copper oxide nanoparticles and bulk copper oxide, combined with indole-3-acetic
      acid, alter aluminum, boron, and iron in Pisum sativum seeds.
AB  - The interaction of CuO nanoparticles (nCuO), a potential nanopesticide, with the
      growth hormone indole-3-acetic acid (IAA) is not well understood. This study
      aimed to evaluate the nutritional components in seeds of green pea (Pisum
      sativum) cultivated in soil amended with nCuO at 50 or 100mgkg-1, with/without
      IAA at 10 or 100MUM. Similar treatments including bulk CuO (bCuO) and CuCl2 were
      set as controls. Bulk CuO at 50mgkg-1 reduced seed yield (52%), compared with
      control. Bulk CuO at 50mgkg-1 and nCuO at 100mgkg-1, plus IAA at 100MUM,
      increased iron in seeds (41 and 42%, respectively), while nCuO at 50mgkg-1, plus
      IAA at 100MUM reduced boron (80%, respect to control and 63%, respect to IAA at
      100MUM). IAA, at 10MUM increased seed protein (33%), compared with control
      (p<=0.05). At both concentrations IAA increased sugar in seeds (20%). Overall,
      nCuO, plus IAA at 10MUM, does not affect the production or nutritional quality of
      green pea seeds.

PMID- 29660877
TI  - Probabilistic modelling and uncertainty analysis of flux and water balance
      changes in a regional aquifer system due to coal seam gas development.
AB  - Large scale development of coal seam gas (CSG) is occurring in many sedimentary
      basins around the world including Australia, where commercial production of CSG
      has started in the Surat and Bowen basins. CSG development often involves
      extraction of large volumes of water that results in depressurising aquifers that
      overlie and/or underlie the coal seams thus perturbing their flow regimes. This
      can potentially impact regional aquifer systems that are used for many purposes
      such as irrigation, and stock and domestic water. In this study, we adopt a
      probabilistic approach to quantify the depressurisation of the Gunnedah coal
      seams and how this impacts fluxes to, and from the overlying Great Artesian Basin
      (GAB) Pilliga Sandstone aquifer. The proposed method is suitable when effects of
      a new resource development activity on the regional groundwater balance needs to
      be assessed and account for large scale uncertainties in the groundwater flow
      system and proposed activity. The results indicated that the extraction of water
      and gas from the coal seam could potentially induce additional fluxes from the
      Pilliga Sandstone to the deeper formations due to lowering pressure heads in the
      coal seams. The median value of the rise in the maximum flux from the Pilliga
      Sandstone to the deeper formations is estimated to be 85ML/year, which is
      considered insignificant as it forms only about 0.29% of the Long Term Annual
      Average Extraction Limit of 30GL/year from the groundwater management area. The
      probabilistic simulation of the water balance components indicates only small
      changes being induced by CSG development that influence interactions of the
      Pilliga Sandstone with the overlying and underlying formations and with the
      surface water courses. The current analyses that quantified the potential maximum
      impacts of resource developments and how they influences the regional water
      balance, would greatly underpin future management decisions.

PMID- 29660878
TI  - Investigation of the behaviour of zero-valent iron nanoparticles and their
      interactions with Cd2+ in wastewater by single particle ICP-MS.
AB  - Zero-valent iron nanoparticles (nZVI) exhibit great potential for the removal of
      metal contaminants from wastewater. After their use, there is a risk that nZVI
      will remain dispersed in remediated water and represent potential nano-threats to
      the environment. Therefore, the behaviour of nZVI after remediation must be
      explored. To accomplish this, we optimised a novel method using single particle
      inductively coupled plasma mass spectrometry (SP-ICP-MS) for the sizing and
      quantification of nZVI in wastewater matrices. H2 reaction gas was used in MS/MS
      mode for the sensitive and interference-free determination of low concentrations
      of nZVI with a low size limit of detection (36nm). This method was applied to
      study the influence of different iron (Fe) loads (0.1, 0.25, 0.5 and 1.0gL-1) and
      water matrices (Milli-Q water, synthetic and effluent wastewater) on the
      behaviour of nZVI, their interactions with Cd2+ and the efficiency of Cd2+
      removal. The aggregation and sedimentation of nZVI increased with settling time.
      Sedimentation was slower in effluent wastewater than in Milli-Q water or
      synthetic wastewater. Consequently, Cd2+ was more efficiently (86%) removed from
      effluent wastewater than from synthetic wastewater (73%), while its removal from
      Milli-Q water was inefficient (19%). The trace amounts of Cd2+ that remained in
      the remediated water were either dissolved or sorbed to residual nZVI. The
      results of the nanoremediation of effluent wastewater with varying Fe loads
      showed that sedimentation was faster at higher initial concentrations of nZVI.
      After seven days of settling, low concentrations of Fe remained in the effluent
      wastewater at Fe loads of 0.5gL-1 or higher, which could indicate that the use of
      nZVI in nanoremediation under the described conditions may not represent an
      environmental nano-threat. However, further studies are needed to assess the
      ecotoxicological impact of Fe-related NPs used for the nanoremediation of
      wastewaters.

PMID- 29660879
TI  - Chloromethane formation and degradation in the fern phyllosphere.
AB  - Chloromethane (CH3Cl) is the most abundant halogenated trace gas in the
      atmosphere. It plays an important role in natural stratospheric ozone
      destruction. Current estimates of the global CH3Cl budget are approximate. The
      strength of the CH3Cl global sink by microbial degradation in soils and plants is
      under discussion. Some plants, particularly ferns, have been identified as
      substantial emitters of CH3Cl. Their ability to degrade CH3Cl remains uncertain.
      In this study, we investigated the potential of leaves from 3 abundant ferns
      (Osmunda regalis, Cyathea cooperi, Dryopteris filix-mas) to produce and degrade
      CH3Cl by measuring their production and consumption rates and their stable carbon
      and hydrogen isotope signatures. Investigated ferns are able to degrade CH3Cl at
      rates from 2.1 to 17 and 0.3 to 0.9MUggdw-1day-1 for C. cooperi and D. filix-mas
      respectively, depending on CH3Cl supplementation and temperature. The stable
      carbon isotope enrichment factor of remaining CH3Cl was -39+/-130/00, whereas
      negligible isotope fractionation was observed for hydrogen (-8+/-190/00). In
      contrast, O. regalis did not consume CH3Cl, but produced it at rates ranging from
      0.6 to 128MUggdw-1day-1, with stable isotope values of -97+/-80/00 for carbon and
      -202+/-100/00 for hydrogen, respectively. Even though the 3 ferns showed clearly
      different formation and consumption patterns, their leaf-associated bacterial
      diversity was not notably different. Moreover, we did not detect genes associated
      with the only known chloromethane utilization pathway "cmu" in the microbial
      phyllosphere of the investigated ferns. Our study suggests that still unknown
      CH3Cl biodegradation processes on plants play an important role in global cycling
      of atmospheric CH3Cl.

PMID- 29660880
TI  - Exploring land use/land cover change and drivers in Andean mountains in Colombia:
      A case in rural Quindio.
AB  - Given that Land Use and Cover Changes (LUCC) and deforestation are activities
      with the highest anthropic intervention on ecosystems and increase the loss of
      biodiversity, this paper explores the LUCC and the main drivers of change in
      Andean mountains, taking a rural area located between the municipalities of
      Montenegro and Quimbaya (Quindio, Colombia) (1954-2009), as a case of study.
      Aerial photographs and geographic information systems (GIS) are used to create
      maps of LUCC, as well as a systemized search of information on LUCC and main
      drivers. The results showed that pastureland presented the largest area during
      all periods, occupying >60% of studied area, while the secondary and mixed
      forests had a contraction from 23% in 1954 to 9% in 2009. The change rates
      evidenced a greater affectation for the secondary forest that lost 86% of its
      initial area through deforestation and transformation processes, while crops
      gained 410% with respect to their initial area. As for the transition matrix,
      about 27.8% of the study area presented transformation from land use and cover
      into other land covers, 14.7% presented deforestation and loss of land cover in
      their initial area, and 57.5% remained unchanged. It is concluded that socio
      economic factors such as livestock farming, agriculture and market prices have
      been an important driver in the modification of the landscape.

PMID- 29660881
TI  - Differences in transport behavior of natural soil colloids of contrasting sizes
      from nanometer to micron and the environmental implications.
AB  - Transport behaviors of nanoparticles (<100nm) and clay fractions (clay particles,
      <2MUm; coarse clay particles, 1-2MUm and fine clay particles, 0.1-1MUm) extracted
      from two natural soils (Inceptisol from Jilin and Oxisol from Hainan, China) were
      investigated in saturated sand columns at 1-30mM NaCl and pH5-9. Increasing NaCl
      concentrations decreased the mobility, while increasing pH increased the mobility
      of soil particles of various sizes. At pH5 and 30mM NaCl, nanoparticles and clay
      fractions exhibited the different transport behaviors, and ripening was observed
      for Inceptisol nanoparticles while blocking for Oxisol nanoparticles in
      breakthrough curves (BTCs). The effluent mass recoveries (MRs) of nanoparticles
      were much more than that of clay particles for both two soils (>1.9-fold) at all
      tested conditions, except for Inceptisol at pH5 and 30mM NaCl (with comparable
      MR). According to Derjaguin-Landau-Verwey-Overbeek (DLVO) calculations and
      particle-collector size ratios, both secondary energy minimum and physical
      straining led to the retention of clay fractions at pH5 and 30mM NaCl, whereas
      primary energy minimum and straining induced by simultaneous aggregation caused
      the retention of nanoparticles. The experimental attachment efficiency between
      soil particles of various sizes and sand collector for both two soils was in the
      order nanoparticles<fine clay particles<clay particles<coarse clay particles,
      indicating that soil nanoparticles had greater mobility than clay fractions.
      Consequently, nanoparticles are suggested to have greater risks to transport
      contaminants to surface and groundwater, once they are released from soils.

PMID- 29660882
TI  - Enantioselective degradation and transformation of the chiral fungicide
      prothioconazole and its chiral metabolite in soils.
AB  - Prothioconazole is a widely used chiral triazole fungicide. In this work, the
      enantioselective degradation and transformation of prothioconazole and its chiral
      metabolite prothioconazole-desthio in five kinds of soils were investigated under
      native and sterile conditions using reversed phase liquid chromatography tandem
      mass spectrometry with a Lux-cellulose-1 column. The results showed that an
      enantioselective degradation was observed with R-prothioconazole preferentially
      degraded in the five soils and enantiomeric fraction values that ranged from 0.32
      to 0.41 under native conditions. Furthermore, the major metabolite
      prothioconazole-desthio was formed rapidly during prothioconazole dissipation.
      The prothioconazole-desthio enantiomers were degraded slowly, and there was a
      slight enantioselectivity with enantiomeric fraction values that ranged from 0.45
      to 0.51 in the Nanjing and Jilin soils. Under sterile conditions, prothioconazole
      and its metabolite enantiomers were more slowly degraded with no
      enantioselectivity. The result of the incubation experiment with single
      enantiomers verified that R- and S-prothioconazole were transformed to R- and S
      prothioconazole-desthio, respectively. No enantiomerization for prothioconazole
      and its chiral metabolite was observed. In addition, the excellent correlation
      between organic matter content and degradation rate indicated that organic matter
      could promote the degradation of prothioconazole and its metabolite enantiomers.
      The data in this study provide the experimental evidence of the stereoselective
      degradation and metabolism of both prothioconazole and its chiral metabolite in
      the environment.

PMID- 29660883
TI  - What drives the carbon mitigation in Chinese commercial building sector? Evidence
      from decomposing an extended Kaya identity.
AB  - Energy efficiency in the building sector is expected to contribute >50% to the
      nationwide carbon mitigation efforts for achieving China's carbon emission peak
      in 2030, and carbon mitigation in Chinese commercial buildings (CMCCB) is an
      indicator of this effort. However, the CMCCB assessment has faced the challenge
      of ineffective and inadequate approaches; therefore, we have followed a different
      approach. Using the China Database of Building Energy Consumption and Carbon
      Emissions as our data source, our study is the first to employ the Logarithmic
      Mean Divisia Index (LMDI) to decompose five driving forces from the Kaya identity
      of Chinese commercial building carbon emissions (CCBCE) to assess the CMCCB
      values in 2001-2015. The results of our study indicated that: (1) Only two
      driving forces (i.e., the reciprocal of GDP per capita of Tertiary Industry in
      China and the CCBCE intensity) contributed negatively remi to CCBCE during 2001
      2015, and the quantified negative contributions denoted the CMCCB values.
      Specifically, the CMCCB values in 2001-2005, 2006-2010, and 2011-2015 were
      123.96, 252.83, and 249.07 MtCO2, respectively. (2) The data quality control
      involving the CMCCB values proved the reliability of our CMCCB assessment model,
      and the universal applicability of this model was also confirmed. (3) The
      substantial achievements of the energy efficiency project in the Chinese
      commercial building sector were the root cause of the rapidly growing CMCCB.
      Overall, we believe that our model successfully bridges the research gap of the
      nationwide CMCCB assessment and that the proposed model is also suitable either
      at the provincial level or in different building climate zones in China.
      Meanwhile, a global-level assessment of the carbon mitigation in the commercial
      building sector is feasible through applying our model. Furthermore, we consider
      our contribution as constituting significant guidance for developing the building
      energy efficiency strategy in China in the upcoming phase.

PMID- 29660884
TI  - Effects of soil water content and elevated CO2 concentration on the monoterpene
      emission rate of Cryptomeria japonica.
AB  - Monoterpenes emitted from plants contribute to the formation of secondary
      pollution and affect the climate system. Monoterpene emission rates may be
      affected by environmental changes such as increasing CO2 concentration caused by
      fossil fuel burning and drought stress induced by climate change. We measured
      monoterpene emissions from Cryptomeria japonica clone saplings grown under
      different CO2 concentrations (control: ambient CO2 level, elevated CO2:
      1000MUmolmol-1). The saplings were planted in the ground and we did not
      artificially control the SWC. The relationship between the monoterpene emissions
      and naturally varying SWC was investigated. The dominant monoterpene was alpha
      pinene, followed by sabinene. The monoterpene emission rates were exponentially
      correlated with temperature for all measurements and normalized (35 degrees C)
      for each measurement day. The daily normalized monoterpene emission rates
      (Es0.10) were positively and linearly correlated with SWC under both control and
      elevated CO2 conditions (control: r2=0.55, elevated CO2: r2=0.89). The slope of
      the regression line of Es0.10 against SWC was significantly higher under elevated
      CO2 than under control conditions (ANCOVA: P<0.01), indicating that the effect of
      CO2 concentration on monoterpene emission rates differed by soil water status.
      The monoterpene emission rates estimated by considering temperature and SWC
      (Improved G93 algorithm) better agreed with the measured monoterpene emission
      rates, when compared with the emission rates estimated by considering temperature
      alone (G93 algorithm). Our results demonstrated that the combined effects of SWC
      and CO2 concentration are important for controlling the monoterpene emissions
      from C. japonica clone saplings. If these relationships can be applied to the
      other coniferous tree species, our results may be useful to improve accuracy of
      monoterpene emission estimates from the coniferous forests as affected by climate
      change in the present and foreseeable future.

PMID- 29660885
TI  - Real-world exhaust temperature profiles of on-road heavy-duty diesel vehicles
      equipped with selective catalytic reduction.
AB  - On-road heavy-duty diesel vehicles are a major contributor of oxides of nitrogen
      (NOx) emissions. In the US, many heavy-duty diesel vehicles employ selective
      catalytic reduction (SCR) technology to meet the 2010 emission standard for NOx.
      Typically, SCR needs to be at least 200 degrees C before a significant level of
      NOx reduction is achieved. However, this SCR temperature requirement may not be
      met under some real-world operating conditions, such as during cold starts, long
      idling, or low speed/low engine load driving activities. The frequency of vehicle
      operation with low SCR temperature varies partly by the vehicle's vocational use.
      In this study, detailed vehicle and engine activity data were collected from 90
      heavy-duty vehicles involved in a range of vocations, including line haul,
      drayage, construction, agricultural, food distribution, beverage distribution,
      refuse, public work, and utility repair. The data were used to create real-world
      SCR temperature and engine load profiles and identify the fraction of vehicle
      operating time that SCR may not be as effective for NOx control. It is found that
      the vehicles participated in this study operate with SCR temperature lower than
      200 degrees C for 11-70% of the time depending on their vocation type. This
      implies that real-world NOx control efficiency could deviate from the control
      efficiency observed during engine certification.

PMID- 29660886
TI  - Removal of emerging contaminants using spent mushroom compost.
AB  - Acetaminophen and sulfonamides are emerging contaminants. Conventional wastewater
      treatment systems fail to degrade these compounds properly. Mycoremediation, is a
      form of novel bioremediation that uses extracellular enzymes of white-rot fungi
      to degrade pollutants in the environment. In this study, spent mushroom compost
      (SMC), which contains fungal extracellular enzymes, was tested for acetaminophen
      and sulfonamides removal. Among the SMCs of nine mushrooms tested in batch
      experiments, the SMC of Pleurotus eryngii exhibited the highest removal rate for
      acetaminophen and sulfonamides. Several fungal extracellular enzymes that might
      be involved in removal of acetaminophen and sulfonamides were identified by
      metaproteomic analysis. The bacterial classes, Betaproteobacteria and
      Alphaproteobacteria, were revealed by metagenomic analysis and may be assisting
      with acetaminophen and sulfonamide removal, respectively, in the SMC of Pleurotus
      eryngii. Bioreactor experiments were used to simulate the capability of Pleurotus
      eryngii SMC for the removal of acetaminophen and sulfonamides from wastewater.
      The results of this study provide a feasible solution for acetaminophen and
      sulfonamide removal from wastewater using the SMC of Pleurotus eryngii.

PMID- 29660887
TI  - Development of water quality criteria of ammonia for protecting aquatic life in
      freshwater using species sensitivity distribution method.
AB  - Ammonia is deemed one of the most important pollutants in the freshwater
      environment because of its highly toxic nature and ubiquity in surface water.
      This study thus aims to derive the criteria for ammonia in freshwater to protect
      aquatic life because there are no water quality criteria for ammonia in Korea.
      Short-term lethal tests were conducted to perform the species sensitivity
      distribution (SSD) method. This method is widely used in ecological risk
      assessment to determine the chemical concentrations to protect aquatic species.
      Based on the species sensitivity distribution method using Korean indigenous
      aquatic biota, the hazardous concentration for 5% of biological species (HC5)
      value calculated in this study was 44mg/L as total ammonia nitrogen (TAN). The
      value of the assessment factor was set at 2. Consequently, the criteria for
      ammonia were derived as 22mg/L at pH7 and 20 degrees C. When the derived value
      was applied to the monitoring data nationwide, 0.51%, 0.09%, 0.18%, 0.20%, and
      0.35% of the monitoring sites in Han River, Nakdong River, Geum River, Youngsan
      River, and lakes throughout the nation, respectively, exceeded this criteria. The
      Ministry of Environment in Korea has been considering introducing water quality
      standard of ammonia for protecting aquatic life. Therefore, our results can
      provide the basis for introducing the ammonia standard in Korea.

PMID- 29660888
TI  - Patterns of ecosystem services supply across farm properties: Implications for
      ecosystem services-based policy incentives.
AB  - In developing countries, the protection of biodiversity and ecosystem services
      (ES) rests on the hands of millions of small landowners that coexist with large
      properties, in a reality of highly unequal land distribution. Guiding the
      effective allocation of ES-based incentives in such contexts requires researchers
      and practitioners to tackle a largely overlooked question: for a given targeted
      area, will single large farms or several small ones provide the most ES supply?
      The answer to this question has important implications for conservation planning
      and rural development alike, which transcend efficiency to involve equity issues.
      We address this question by proposing and testing ES supply-area relations
      (ESSARs) around three basic hypothesized models, characterized by constant (model
      1), increasing (model 2), and decreasing increments (model 3) of ES supply per
      unit of area or ES "productivity". Data to explore ESSARs came from 3384 private
      landholdings located in southern Chile ranging from 0.5ha to over 30,000ha and
      indicators of four ES (forage, timber, recreation opportunities, and water
      supply). Forage provision best fit model 3, which suggests that targeting several
      small farms to provide this ES should be a preferred choice, as compared to a
      single large farm. Timber provision best fit model 2, suggesting that in this
      case targeting a single large farm would be a more effective choice. Recreation
      opportunities best fit model 1, which indicates that several small or a single
      large farm of a comparable size would be equally effective in delivering this ES.
      Water provision fit model 1 or model 2 depending on the study site. The results
      corroborate that ES provision is not independent from property area and therefore
      understanding ESSARs is a necessary condition for setting conservation incentives
      that are both efficient (deliver the highest conservation outcome at the least
      cost) and fair for landowners.

PMID- 29660889
TI  - Understanding the retention and fate prediction of copper ions in single and
      competitive system in two soils: An experimental and numerical investigation.
AB  - The concept of sponge city has become very popular with major thrust on design of
      waste containment systems such as biofilter and green roofs. Factors that may
      influence pollutant ions retention in these systems will be soil type and also
      their interactions. The study investigated single and competitive interaction of
      copper in two soils and its influence on the fate prediction. Freundlich and
      Langmuir nonlinear isotherms were selected to quantify the retention results.
      Series of numerical simulations were conducted to model 1 D advection-dispersion
      transport for the two soils and analyse the role of isotherms. The results
      indicated that contaminant fate prediction of copper-soil interaction based on
      the two non-linear isotherms was different for both single and that in
      competition. Retardation factor obtained from Freundlich (RF) isotherm predicts
      more than Langmuir (RLa). This observation is more explicit at the higher range
      of equilibrium concentration. Fate prediction based on retardation value obtained
      from retention isotherms exhibited some anomalous trends contradicting the
      experimental findings due to inherent assumptions in governing equations. The
      necessity to have an approximate assessment of contaminant concentration in the
      field to effectively use contaminant retention results for accurate fate
      prediction is highlighted here. The study is important for modellers in design or
      analysis of biolfilter system (sponge city), where multiple ions tend to exist in
      waste water.

PMID- 29660890
TI  - Initial changes in soil properties and carbon sequestration potential under
      monocultures and short-rotation alley coppices with poplar and willow after three
      years of plantation.
AB  - Initial changes in soil structure and C stocks were studied under short-rotation
      coppices (SRC) planted on former cropland near Gottingen, Central Germany.
      Plantations were established either as monocultures with willow (Willow-SRC) or
      poplar (Poplar-SRC), or as an agroforestry system with willow strips and
      grassland alleys in between (Willow-AF). A neighbouring cropland served as a
      control. Three sampling campaigns were applied in this study. The first sampling
      was conducted at a fine scale to reveal the differences in soil C with depth
      (i.e. 0-3, 3-6, 6-9, 9-12, 12-15, 15-20, 20-30cm). Here, results indicated the
      main differences between plantations in 0-3, 3-20 and 20-30cm layers. These soil
      depths were therefore chosen for the second sampling campaign to reveal
      differences in aggregate composition, C accumulation in aggregates and density
      fraction, and microbial biomass carbon (MBC) between plantations. Furthermore,
      quality of soil organic matter and amount of C mineralised by microorganisms were
      estimated by an incubation experiment. Results here indicated two times higher
      CO2 emissions from the top layer than from the lower layers under SRCs, as well
      as higher MBC in SRCs (490-788.7MUgCg-1) than in cropland (266.4MUgCg-1). The
      results of the third sampling on the texture of respective soil horizons
      indicated a significant correlation (R2=78%) of soil clay to C at 0-3cm depth. It
      was concluded that aggregation and C in microbial biomass and free light
      fractions were the first indicators of soil quality improvement after conversion
      of arable land to SRC plantations.

PMID- 29660891
TI  - Soil microbial communities and glyphosate decay in soils with different herbicide
      application history.
AB  - This study evaluates the glyphosate dissipation under field conditions in three
      types of soil, and aims to determine the importance of the following factors in
      the environmental persistence of herbicide: i) soil bacterial communities, ii)
      soil physicochemical properties, iii) previous exposure to the herbicide. A soil
      without previous record of GP application (P0) and two agricultural soils, with 5
      and >10years of GP exposure (A5 and A10) were subjected to the application of
      glyphosate at doses of 3mg.kg-1. The concentration of GP and AMPA was determined
      over time and the dynamics of soil bacterial communities was evaluated using 16S
      ARN ribosomal gene amplicon-sequencing. The GP exposure history affected the rate
      but not the extent of GP biodegradation. The herbicide was degraded rapidly, but
      P0 soil showed a dissipation rate significantly lower than soils with
      agricultural history. In P0 soil, a significant increase in the relative
      abundance of Bacteroidetes was observed in response to herbicide application.
      More generally, all soils displayed shifts in bacterial community structure,
      which nevertheless could not be clearly associated to glyphosate dissipation,
      suggesting the presence of redundant bacteria populations of potential degraders.
      Yet the application of the herbicide prompted a partial disruption of the
      bacterial association network of unexposed soil. On the other hand, higher values
      of linear (Kd) and nonlinear (Kf) sorption coefficient in P0 point to the
      relevance of cation exchange capacity (CEC), clay and organic matter to the
      capacity of soil to adsorb the herbicide, suggesting that bioavailability was a
      key factor for the persistence of GP and AMPA. These results contribute to
      understand the relationship between bacterial taxa exposed to the herbicide, and
      the importance of soil properties as predictors of the possible rate of
      degradation and persistence of glyphosate in soil.

PMID- 29660892
TI  - Distribution of fragrances and PAHs in the surface seawater of the Sicily
      Channel, Central Mediterranean.
AB  - The Mediterranean Sea is highly influenced by several anthropic pressures,
      including different kinds of organic pollutants. Fragrance Materials (FMs) and
      Polycyclic Aromatic Hydrocarbons (PAHs) were investigated in the surface seawater
      of the Sicily Channel in offshore and coastal areas. Total concentrations of FMs
      and PAHs resulted respectively up to 112ngL-1 and 43ngL-1, with similar
      distributions of both classes of analytes. Low values were detected in some
      coastal samples, due to the upwelling of deep and unpolluted waters, while the
      presence of gyres probably accumulates contaminants in offshore areas. Confirming
      previous works, the allergenic and oestrogenic Salicylates generally resulted the
      most abundant FMs and diagnostic ratios indicated combustion processes as the
      sources of PAHs. The coupling of the well-known PAHs with a new class of Personal
      Care Products (PCPs) helped the identification of the major environmental
      drivers: the results highlighted the role of mesoscale hydrodynamics and
      suggested long-range atmospheric transport as key factors. The first detection of
      the selected FMs in open sea areas supports the hypothesis of their environmental
      persistence.

PMID- 29660893
TI  - GIS-based multi-criteria site selection for zebra mussel cultivation: Addressing
      end-of-pipe remediation of a eutrophic coastal lagoon ecosystem.
AB  - Farming of shellfish and seaweeds is a tested tool for mitigating eutrophication
      consequences in coastal environments, however as many other marine economic
      activities it should be a subject of marine spatial planning for designating
      suitable sites. The present study proposes site selection framework for
      provisional zebra mussel farming in a eutrophic lagoon ecosystem, aimed primarily
      at remediation purposes. GIS-based multi-criteria approach was applied, combining
      data from empirical maps, numerical models and remote sensing to estimate
      suitability parameters. Site selection and prioritisation of suitable areas
      considered 15 environmental and socio-economic criteria, which contributed to 4
      optimisation models (settlement, growth and survival of mussels, environmental
      and socio-economic) and 3 predefined scenarios representing provisional goals of
      mussel cultivation: spat production, biomass production and bioremediation. The
      relative importance of each criterion was assessed utilizing the Analytical
      Hierarchy Process. Site suitability index was calculated and the final result of
      the site selection analysis was summarized for 3 scenarios and overall
      suitability map. Four suitability classes (unsuitable, least, moderately and most
      suitable) were applied, and 3 most suitable zones for provisional zebra mussel
      cultivation with 12 candidate sites were selected accordingly. The integrated
      approach presented in this study can be adjusted for designating zebra mussel
      farming sites in other estuarine lagoon ecosystems, or cultivation of other
      mussel species for bioremediation purposes. The analytical framework and the
      workflow designed in this study are also adoptable for addressing other
      aquaculture-related spatial planning issues.

PMID- 29660894
TI  - Overall survival of elderly patients with breast cancer is not related to breast
      cancer specific survival: A single institution experience in Japan.
AB  - BACKGROUND: As the aging population grows, the number of elderly breast cancer
      patients has rapidly increased especially in Japan; a suitable treatment for
      elderly patients, considering chronic comorbidities and treatment tolerance, is
      urgently needed. METHODS: In this retrospective study, 286 elderly breast cancer
      patients were investigated. Tumor characteristics and survival outcome were
      compared between 70-79-year-old and >= 80-year-old groups. Disease-free survival,
      overall survival, and breast cancer-specific survival were compared, and the
      effect of variables was analyzed statistically. For resectable cases, prognoses
      were compared based on treatment (standard therapy or undertreated). RESULTS:
      Tumor characteristics were similar between groups, but the Ki-67 labeling index
      tended to be higher in older patients. Elderly patients with resectable cancer
      tended to be undertreated. During the median 59-month follow-up period, overall
      survival was significantly worse in the >=80-year-old than in the 70-79-year-old
      group (p < 0.001), but disease-free and breast cancer-specific survivals were
      equivalent. Recurrence or death event hazard rates tended to be lower in patients
      receiving standard treatment. CONCLUSIONS: Standard multidisciplinary treatment
      for breast cancer prevents recurrence and metastasis and tends to extend breast
      cancer-specific survival even in elderly patients.

PMID- 29660895
TI  - Rheological characterization of an in vitro model for salmonid chyme to quantify
      changes in feed composition.
AB  - BACKGROUND: Developments in the production of aquacultural salmonid feeds in the
      last 20 years have led to extruded diets with extremely low water content and a
      shift from mainly marine fish based ingredients towards plant content. These
      changes expose the industry to the vagaries of the highly dynamic plant protein
      market. Resulting variations in the precise composition of aqua feeds may carry
      unpredictable consequences for water quality, since some plant ingredients cause
      undesirable reductions in the mechanical stability of faeces. Dietary supplements
      known as binders that enhance the stability of faeces have the potential to
      mitigate these issues, but may also bring negative effects. OBJECTIVE AND
      METHODS: The present study employs an in vitro model to perform the first
      fundamental rheological characterization of salmonid chyme, and a factorial
      experiment designed to investigate the impacts of the presence of rheologically
      active substances. RESULTS: The highest mean viscosity values were measured for a
      treatment containing a 2:1 ratio of tara gum:xanthan gum, resulting in chyme four
      times more viscous than a control formulation containing the same amount of
      water. Shear resistance was quantified by analyses of slopes fitting the
      frequency sweep measurements. CONCLUSIONS: These data open a new statistical
      approach to monitoring the consequences of market-driven changes in aqua feed
      composition and their impacts on the nutrition, health or performance of farmed
      fish.

PMID- 29660896
TI  - A physiological exploration on operational stance and occupational
      musculoskeletal problem manifestations amongst construction labourers of West
      Bengal, India.
AB  - BACKGROUND: A huge number of labourers work in the construction industry in India
      both in organized and unorganized sectors. The construction labourers most often
      work for an extended period of time and they are compelled to uphold altered
      static and dynamic operational stance in awkward positions during the complete
      period of work which raises the demand on the musculoskeletal system and may lead
      to work related musculoskeletal disorders (WRMSDs). OBJECTIVE: This study is
      intended to explore the operational stance and occupation related musculoskeletal
      manifestations amongst the construction labourers. One hundred sixty four male
      labourers from different construction sites in West Bengal were randomly taken
      for this study. METHODS: A modified Nordic questionnaire on MSD and the 12 item
      General Health Questionnaire (GHQ12) were administered on the construction
      labourers. Rapid Entire Body Assessment (REBA) and Ovako Work Analysis System
      (OWAS) methods were applied to analyze the operational stance. Finally,
      discomfort levels of the specific operational stance were calculated by the use
      of risk level and BPD scale. RESULTS: The study revealed that most of the
      construction labourers habitually worked in awkward operational stance and were
      affected by altering musculoskeletal manifestations like pain in low back, neck,
      and wrist. We also found that there is a significant (p< 0.05) association
      between the intensity of pain feeling, age, year of working experience and risk
      level of the individual working postures of the labourers. CONCLUSION:
      Appropriate work-rest schedule, amendments of some working techniques and use of
      some ergonomically designed equipment may lessen the WRMSDs and improve the
      health eminence of construction labourers in unorganized sectors.

PMID- 29660897
TI  - Effects of group exercise on functional abilities: Differences between physically
      active and physically inactive women.
AB  - BACKGROUND: Aerobic exercises to music can have a positive effect on functional
      and motor skills of an exerciser, their health, as well as an aesthetic and socio
      psychological component. OBJECTIVE: The objective of this study was to determine
      the effects of reactive exercising in a group on functional capabilities in
      physically active and physically inactive women. METHODS: A prospective study
      included 64 healthy women aged 40-60 years. The sample was divided into the
      experimental group (N= 36), i.e. physically active women who have been engaged in
      recreational group exercises at the Faculty of Sport and Physical Education,
      University of Novi Sad, Serbia, and the control group (N= 28), which consisted of
      physically inactive women. All the participants were monitored using the same
      protocol before and after the implementation of the research. All women had their
      height, weight and body mass index measured as well as their spiroergometric
      parameters determined according to the Bruce protocol. RESULTS: A univariate
      analysis of variance has shown that there is a statistically significant
      difference between the experimental group and the control group in maximum speed,
      the total duration of the test, relative oxygen consumption, absolute oxygen
      consumption and ventilation during the final measurement. After the training
      intervention, the experimental group showed improvements in all the parameters
      analyzed compared with pretest values. CONCLUSION: The recreational group
      exercise model significantly improves aerobic capacity and functioning of the
      cardiovascular system. Therefore, it is essential for women to be involved more
      in any form of recreational group exercising in order to improve functional
      capacity and health.

PMID- 29660898
TI  - Down-regulation of long non-coding RNA GAS5-AS1 and its prognostic and diagnostic
      significance in hepatocellular carcinoma.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is the most common solid tumor in
      global range, with high degree of malignancy and poor prognosis. But the
      relationship between the expression of GAS5-AS1 and HCC is not documented. This
      study aimed to profile GAS5-AS1 expression signature and then to explore its
      clinical significance in HCC. METHODS: Quantitative real-time PCR (RT-qPCR) was
      performed to detect the expression of GAS5-AS1 in 83 pairs of HCC surgical
      tissues and adjacent normal liver tissues. We also performed RT-qPCR on plasma
      samples of 156 patients and 58 healthy controls. RESULTS: We found that GAS5-AS1
      was down-regulated in HCC tissues (P< 0.01). Correlation analysis showed that the
      expression of GAS5-AS1 was notably associated with differentiation (High/Moderate
      vs Low, P= 0.031), tumor-node-metastasis (TNM) stage (I~II vs III~IV, P= 0.020)
      and glucose levels (< 6.2 vs? 6.2, P= 0.047) in HCC patients. The overall
      survival analysis showed that patients with lower GAS5-AS1 expression had a
      relatively poor prognosis. Univariate and multivariate analysis elaborated that
      GAS5-AS1 was an independent prognostic factor for HCC patients. The area under
      the ROC (AUCROC) demonstrated that GAS5-AS1 presented a high accuracy (AUC =
      0.824, 95% CI: 0.741-0.906) for distinguishing HCC from the cirrhosis. When
      differentiating HCC cases with AFP < 200 ng/ml from the cirrhosis and hepatitis B
      whose AFP levels were also below 200 ng/ml, GAS5-AS1 had the high sensitivity
      (89.5%, 89.5%, respectively). CONCLUSIONS: GAS5-AS1 could be considered as a
      potential prognostic and diagnostic marker in HCC. However, the potential
      clinical application value of GAS5-AS1 still needs to be further illustrated.

PMID- 29660899
TI  - Plasma exosome levels in non-small-cell lung cancer: Correlation with
      clinicopathological features and prognostic implications.
AB  - BACKGROUND: Biomarker studies revealed important clinical significance of exosome
      for cancer patients. However, there is currently no consensus on exosome
      quantification methods. METHODS: Bicinchoninic acid (BCA) method,
      acetylcholinesterase (AChE) method and nanoparticle tracking analysis (NTA) were
      utilized to quantify 20 plasma exosome samples, and interrelations between these
      three methods were explored. Associations of plasma exosome levels with
      characteristics and prognosis of 208 non-small-cell lung cancer (NSCLC) patients
      were investigated. RESULTS: Results of the three methods for exosome
      quantification were significantly correlated with each other. Correlation
      coefficient between AChE and NTA (r= 0.79, P< 0.001) was greater than that
      between BCA and NTA (r= 0.64, P= 0.003). Plasma exosome levels of 208 NSCLC
      patients were then quantified with AChE method. Exosome level was significantly
      associated with tumour stage (P< 0.001) and the history of chronic obstructive
      pulmonary disease (P= 0.023). Cox proportional hazard analysis demonstrated that
      higher exosome level was independently associated with poorer overall survival
      (P= 0.033; hazard ratio = 1.72, 95% confidence interval: 1.05-2.83). CONCLUSIONS:
      Plasma exosome level correlates with tumor stage and the history of chronic
      obstructive pulmonary disease, and may serve as a prognostic factor for NSCLC.

PMID- 29660900
TI  - Decreased BRMS1L expression is correlated with glioma grade and predicts poor
      survival in glioblastoma via an invasive phenotype.
AB  - AIMS: To evaluate the prognostic and clinicopathological features of glioma with
      BRMS1L expression. METHODS: Total 120 glioma samples were obtained as discovery
      cohort. CGGA, GSE and TCGA datasets were obtained as validation sets.
      Furthermore, Kaplan-Meier survival and multivariate Cox analysis were used to
      evaluate the survival distributions. Moreover, the functional role of BRMS1L was
      also analyzed by transwell assay. RESULTS: In the discovery cohort, decreased
      BRMS1L expression was significantly associated with high-grade glioma as well as
      the higher mortality in survival analysis (log-rank test, p< 0.01). And the three
      validation cohorts showed the similar results. Furthermore, BRMS1L act as an
      independent prognostic factor in glioblastoma patients. Additionally, functional
      assay showed that ectopic of BRMS1L suppressed glioma cells' invasion.
      CONCLUSION: BRMS1L plays as an anti-oncogene in GBM and indicates a new potential
      therapeutic target.

PMID- 29660902
TI  - Effect of Rho kinase inhibitor fasudil on the expression ET-1 and NO in rats with
      hypoxic pulmonary hypertension.
AB  - OBJECTIVE: This study aims to study the effect of Rho kinase inhibitor fasudil on
      the expression endothelin-1 (ET-1) and nitric oxide (NO) in rats with hypoxic
      pulmonary hypertension (HPH). METHODS: Twenty-four male SD rats were randomly
      divided into three groups: control group, model group (HPH group) and HPH+fasudil
      group. The rat HPH model was established by intermittent hypoxia (IH) at
      atmospheric pressure. Mean pulmonary artery pressure (mPAP), right ventricular
      hypertrophy index (RVHI), ET-1 and NO levels, and pulmonary vascular structural
      changes were observed in all groups. RESULTS: MPAP, RVHI and ET-1 levels were
      significantly higher in HPH group than in control group, while NO was
      significantly lower than in control group. In addition, mPAP, RVHI and ET-1 were
      significantly lower in the HPH+fasudil group than in the HPH group. In the HPH
      group, ET-1 level was significantly and positively correlated with mPAP and RVHI,
      NO was negatively correlated with mPAP and RVHI levels, and ET-1 level was
      significantly and negatively correlated with NO level. In the HPH group,
      pulmonary arteriolar walls were generally thickened, and lumen stenosis was
      obvious; while after fasudil treatment, pulmonary arteriolar wall thickening and
      stenosis degree were significantly reduced. CONCLUSION: Fasudil can significantly
      reduce ET-l level and increase NO level in HPH rats, suppressing the development
      of pulmonary arterial hypertension.

PMID- 29660901
TI  - No evidence of pancreatic ductal adenocarcinoma specific autoantibodies to Ezrin
      in a liquid phase LIPS immunoassay.
AB  - BACKGROUND: Sensitive and specific biomarkers of Pancreatic Ductal Adenocarcinoma
      (PDAC) are desperately needed to allow early diagnosis and improve patient's
      survival. Ezrin autoantibodies were recently described as present in 93% of PDAC
      patients and 40% of healthy subjects who later developed PDAC. However, another
      prospective study failed to replicate these findings. Both studies were based on
      the use of a solid phase ELISA immunoassay. OBJECTIVE: We aimed at re-evaluating
      the usefulness of Ezrin autoantibodies as PDAC biomarkers using the Luciferase
      Immuno Precipitation System (LIPS), an alternative immunoassay format that found
      successful application for the measurement of autoantibodies against pancreatic
      autoantigens. METHODS: We produced a NanoluciferaseTM tagged Ezrin (NLuc-Ezrin).
      NLuc-Ezrin was then used as antigen in LIPS to test for Ezrin autoantibodies
      patients affected by PDAC (n= 40), other pancreatic diseases (OPD, n= 50), and
      healthy controls (n= 60). RESULTS: Overall, binding in liquid phase to Ezrin by
      serum antibodies was rare and low titer. Furthermore, we did not find
      statistically significant differences in the prevalence of Ezrin autoantibodies
      between patients affected by either PDAC or OPD compared to control. CONCLUSIONS:
      Our results do not confirm the usefulness of Ezrin autoAbs as biomarker of PDAC.

PMID- 29660903
TI  - Complex cystic and solid breast lesions: Diagnostic performance of conventional
      ultrasound, strain imaging and point shear wave speed measurement.
AB  - OBJECTIVE: To assess the performance of conventional high frequency ultrasound
      (US) and US elastography in diagnosis of complex cystic and solid breast lesions.
      METHODS: Ninety three lesions in 93 patients underwent conventional US and US
      elastography, including strain elastography, acoustic radiation force impulse
      (ARFI) imaging, and point shear wave speed (SWS) measurement. RESULTS:
      Pathological examination revealed 31 (33.3%) of the 93 lesions were malignant and
      the remaining 62 (66.7%) were benign. Multivariate analysis showed that elder
      patient (OR: 25.301), internal vascularity (OR: 4.518), and not circumscribed
      margin (OR: 3.813) were independent predictors for malignancy, while
      predominately cystic lesions (OR: 0.178) was a predictor for benign lesions (all
      p < 0.05). Invalid SWS measurement was occurred in 19 of 31 (61.3%) malignant
      lesions and 16 of 62 (25.8%) benign lesions, respectively (p < 0.05). The mean
      SWS value for malignant lesions was significantly lower than that for benign
      ones, being 1.60+/-0.63 m/s (range, 0.68-2.70 m/s) versus 2.33+/-0.77 m/s (range,
      0.67-3.97 m/s) (p < 0.05). Areas under the ROC curve (Azs) for Breast Imaging
      Reporting and Data System (BI-RADS) assessment, strain elasticity score, ARFI
      imaging and valid point SWS measurement were 0.844, 0.734, 0.763 and
      0.778,respectively. CONCLUSIONS: US BI-RADS category, strain elastography score,
      ARFI imaging patterns and point SWS measurement are useful for malignancy
      prediction of complex cystic and solid breast lesions. The result that SWS for
      malignant lesions is lower than benign one should be carefully interpreted since
      invalid SWS measurement is excluded for analysis. The true stiffness of malignant
      cystic and solid lesions should be further evaluated with a new generation of two
      dimensional SWS imaging.

PMID- 29660904
TI  - Ryanodine receptor antagonism alleviates skeletal muscle ischemia reperfusion
      injury by modulating TNF-alpha and IL-10.
AB  - BACKGROUND: Intracellular calcium overload has been implicated in various
      pathological conditions including ischemia reperfusion injury. This study aims to
      explore the effect and probable mechanism of dantrolene, a ryanodine receptor and
      intracellular calcium antagonist, on the skeletal muscle ischemia reperfusion
      injury. MATERIALS AND METHODS: SD rats were randomly divided into three groups:
      sham group which underwent anaesthesia and exposure of femoral vein, reperfusion
      group that received 2 h ischemia and the amount of diluent via femoral vein
      before 4 h reperfusion, dantrolene group that underwent 2 h ischemia and was
      given 2 mg/kg dantrolene via femoral vein before 4 h reperfusion. The parameters
      measured at the end of reperfusion included serum maleic dialdehyde (MDA), tissue
      myeloperoxidase (MPO) and muscle histology, as well as serum TNF-alpha and IL-10.
      RESULTS: Levels of MDA, MPO and TNF-alpha increased in the reperfusion group,
      whereas the relevant expressions in the dantrolene group decreased significantly.
      Histological examination demonstrated significant improvements between the same
      both groups. IL-10 reflected the protection observed above with a significant up
      regulation of expression after dantrolene administration. CONCLUSION: Ryanodine
      receptor antagonist dantrolene exerted a significant protective effect against
      the inflammatory injury of skeletal muscle ischemia reperfusion. The underlying
      molecular mechanism is probably related to the suppression of TNF-alpha levels
      and the increment of IL-10 expression.

PMID- 29660905
TI  - Differences in time-domain and spectral indexes of skin-surface laser-Doppler
      signals between controls and breast-cancer subjects.
AB  - BACKGROUND: There is an urgent need to improve the early diagnosis of breast
      cancer. OBJECTIVE: The present study applied spectral and beat-to-beat analyses
      to laser-Doppler (LDF) data sequences measured on the skin surface on the back of
      the right hands, with the aim of comparing the different peripheral
      microcirculatory-blood-flow (MBF) perfusion condition between breast-cancer and
      control subjects. METHODS: ECG and LDF signals were obtained simultaneously and
      noninvasively from 23 breast-cancer patients and 23 age-matched control subjects.
      Time-domain beat-to-beat indexes and their variability parameters were
      calculated. Spectral indexes were calculated using the Morlet wavelet transform.
      RESULTS: The beat-to-beat LDF pulse width and its variability were significantly
      smaller in cancer patients than in the controls. The energy contributions of
      endothelial-, neural-, and myogenic-related frequency bands were also
      significantly smaller in cancer patients. CONCLUSIONS: The present study has
      revealed significant differences in the beat-to-beat and spectral indexes of skin
      surface-acquired LDF signals between control subjects and breast-cancer patients.
      This illustrates that LDF indexes may be useful for monitoring the changes in the
      MBF perfusion condition induced by breast cancer. Since the breast-cancer
      patients were at TNM stages 0- 2, the present findings may aid the development of
      indexes for detecting breast cancer.

PMID- 29660906
TI  - Viscometer validation studies for routine and experimental hemorheological
      measurements.
AB  - BACKGROUND: Viscosity measurement is challenging due to the internal properties
      of blood and the artifacts deriving from the various viscometer systems.
      OBJECTIVE: We aimed to determine the pitfalls of a cone-plate viscometer
      (Brookfield DV-III Ultra LV) before starting measurements and compare it to our
      capillary type model (Hemorex Hevimet 40). Effects of sample storage and thermal
      calibration were assessed as well. METHODS AND RESULTS: Intra-observer
      variability was studied by 10 replicate measurements of 7 blood samples, mean
      coefficients of variation were less than 5%. Instruments were compared by
      measuring 26 blood samples, an average difference of 7% in WBV and 10% in PV was
      observed. 9 blood samples were stored at 4 degrees C, 22 degrees C and 37 degrees
      C up to 48 hours to study the effect of storage on viscosity values. WBV at 50
      and 100 s-1 became significantly lower after 3 hours at 37 degrees C (p < 0.05).
      WBV at higher shear rates and PV remained constant at all temperatures. To
      evaluate the possibility of measuring one sample at different temperatures, 8
      blood samples were measured at 40 degrees C with the device calibrated both at 20
      degrees C and 40 degrees C; no significant difference was observed. CONCLUSIONS:
      Thorough validation studies are required before starting experimental and routine
      viscosity measurements.

PMID- 29660907
TI  - Pulse wave velocity is lower in trained than in untrained sickle cell trait
      carriers.
AB  - BACKGROUND: Sickle cell trait (SCT) is a benign condition of sickle cell disease.
      Nevertheless, previous reports showed that SCT carriers have increased blood
      viscosity and decreased vascular reactivity compared to non-SCT carrier. The
      benefit of regular exercise on vascular function has been well documented in the
      general population but no study focused on the SCT population. PURPOSE: The aim
      of our study was to compare arterial stiffness and blood viscosity between
      trained and untrained SCT carriers, as well as a group of untrained non-SCT.
      METHODS: Arterial stiffness (finger-toe pulse wave velocity) and blood viscosity
      were evaluated in untrained non-SCT carriers (n = 10), untrained SCT carriers (n
      = 23) and trained SCT carriers (n = 17) who reported at least 10 hours of
      physical exercise per week. RESULTS: Untrained SCT carriers had higher pulse wave
      velocity (p = 0.032) and blood viscosity (p < 0.001) than their trained
      counterparts. In addition, untrained SCT carriers had higher blood viscosity (p <
      0.001) than the untrained non-SCT group. A positive association was noted between
      blood viscosity and pulse wave velocity in the whole study population.
      CONCLUSION: Our study suggests that regular exercise may be beneficial for the
      vascular function of SCT carriers.

PMID- 29660908
TI  - Evaluation of shear wave elastography for differential diagnosis of breast
      lesions: A new qualitative analysis versus conventional quantitative analysis.
AB  - OBJECTIVE: To evaluate a special kind of ultrasound (US) shear wave elastography
      for differential diagnosis of breast lesions, using a new qualitative analysis
      (i.e. the elasticity score in the travel time map) compared with conventional
      quantitative analysis. METHODS: From June 2014 to July 2015, 266 pathologically
      proven breast lesions were enrolled in this study. The maximum, mean, median,
      minimum, and standard deviation of shear wave speed (SWS) values (m/s) were
      assessed. The elasticity score, a new qualitative feature, was evaluated in the
      travel time map. The area under the receiver operating characteristic (AUROC)
      curves were plotted to evaluate the diagnostic performance of both qualitative
      and quantitative analyses for differentiation of breast lesions. RESULTS: Among
      all quantitative parameters, SWS-max showed the highest AUROC (0.805; 95% CI:
      0.752, 0.851) compared with SWS-mean (0.786; 95% CI:0.732, 0.834; P = 0.094), SWS
      median (0.775; 95% CI:0.720, 0.824; P = 0.046), SWS-min (0.675; 95% CI:0.615,
      0.731; P = 0.000), and SWS-SD (0.768; 95% CI:0.712, 0.817; P = 0.074). The AUROC
      of qualitative analysis in this study obtained the best diagnostic performance
      (0.871; 95% CI: 0.825, 0.909, compared with the best parameter of SWS-max in
      quantitative analysis, P = 0.011). CONCLUSIONS: The new qualitative analysis of
      shear wave travel time showed the superior diagnostic performance in the
      differentiation of breast lesions in comparison with conventional quantitative
      analysis.

PMID- 29660909
TI  - The effect of trimetazidine in reducing the ischemia-reperfusion injury in rat
      epigastric skin flaps.
AB  - BACKGROUND: Ischemia-reperfusion injury may lead to insufficient microcirculation
      and results in partial flap loss during the free flap surgeries. OBJECTIVE: This
      study aimed to investigate the effect of trimetazidine (TMZ) on oxidative stress,
      inflammation and histopathological changes, using the epigastric skin flap model
      in rats. METHODS: 40 male Wistar rats were used, that were divided into four
      groups. Control group, non-treated ischemic (I/R)-group and two trimetazidine
      treated groups (preischemically, postischemically) were established. To create
      ischemia in the skin flap, the superficial epigastric vessels were clamped for
      six hours, followed by twenty-four hours of reperfusion. Blood samples and
      biopsies from skin flaps were collected at the end of the reperfusion period. The
      inflammatory response, the degree of oxidative stress (by measuring the plasma
      level of malondialdehyde (MDA), reduced glutathione (GSH); sulfhydryl (-SH)
      groups) and histopathological changes were evaluated. RESULTS: Inflammatory
      response, and oxidative stress were significantly attenuated in the trimetazidine
      treated groups, compared to the non-treated ischemic group. Histopathological
      findings were also correlated with the biochemical results. CONCLUSION: In our
      study trimetazidine could reduce the ischaemia-reperfusion injury, even after an
      unexpected ischemic period, so it is a promising drug during free tissue
      transfer, replantation or during revascularization procedures in the future.

PMID- 29660910
TI  - Pneumoperitoneum induced ischemia-reperfusion injury of the peritoneum -
      Preconditioning may reduce the negative side-effects caused by carbon-dioxide
      pneumoperitoneum - Pilot study.
AB  - INTRODUCTION: Laparoscopy is more beneficial than the conventional open
      technique, however the pneumoperitoneum created may have an ischemic side effect.
      OBJECTIVE: Our aim was to evaluate the protective effects of preconditioning
      during laparoscopic cholecystectomies (LC). METHODS: 30 patients were randomized
      into 2 groups: I. PreC (preconditioning: 5 min. inflation, 5 min. deflation,
      followed by conventional LC), II: LC (conventional LC). Blood samples were taken
      before hospitalization (C = control), before surgery, after anaesthesia (B.S.),
      after surgery (A.S.) and 24 hours after the procedure (24 h). Measured parameters
      were: malondialdehyde (MDA), reduced glutathione (GSH), sulfhydril groups (-SH),
      superoxide-dismutase (SOD), catalase (CAT), myeloperoxidase (MPO), length of
      hospitalization and pain (VAS = visual analogue scale). RESULTS: Compared to the
      BS levels, no significant changes were detected in SOD's activity and MDA levels.
      GSH concentrations were significantly increased in the PreC group after
      operation. SH-, MPO, CAT and liver function enzymes were not significantly
      different. Hospitalization was shorter in the PreC group. Based on the VAS score
      patients had less pain in the PreC group. CONCLUSION: Significant differences
      concerning PreC group were found in GSH values. In the PreC group pain decreased
      by 2-2.5 units following the procedure, 24 h after surgery, and hospitalisation
      was also significantly shorter. In our pilot study the potential protective
      effect of preconditioning could be defined.

PMID- 29660911
TI  - The effects of different remote ischemic conditioning on ischemia-induced failure
      of microvascular circulation in humans.
AB  - BACKGROUND: Intermittent ischemia in remote tissues can be applied before
      ischemic injury, during ischemic injury or at the beginning of reperfusion of an
      index organ ischemia. The aim of this study was to investigate the effect of
      Remote Ischemic Conditioning (RIC) of the leg on changes in ischemia-induced the
      microvascular functions of the arm. MATERIAL AND METHODS: Ischemic microvascular
      injury was induced by arm ischemia (20 min) and reperfusion in healthy,
      nonsmoker, male volunteers (ischemia group-ISC, n: 9). In another group of
      volunteers, to investigate the effects of remote organ ischemic conditioning 5
      cycles of reperfusion followed by leg ischemia (each lasting 60 seconds) were
      applied either before (preRIC, n:11), or during (perRIC, n:12) or immediately
      after (postRIC, n:9) 20 minutes of arm ischemia. The microvascular flow of arm
      was assessed before and after ischemia using iontophoresis of the endothelium
      derived nitric oxide (NO) releaser acetylcholine (ACh) and the endothelium
      independent NO donor sodium nitroprusside (SNP). Changes in microvascular blood
      flow were measured using Laser Doppler imaging. The plasma level of biomarkers
      related to endothelial function such as nitric oxide (NO), asymmetric
      dimethylarginine (ADMA), total antioxidant capacity (TAC) and hydrogen sulphide
      (H2S) were measured. RESULTS: No difference was determined between the groups in
      terms of age, BMI or blood biochemicals reflecting cardiovascular status. ACh
      caused a rise in microvascular blood flow in a charge dependent manner. The ACh
      induced flow increase was not significantly depressed by ischemia and not
      affected by any of the types of RIC in the study subjects. The increase in SNP
      induced microvascular flow was significantly decreased in the ISC, perRIC and
      postRIC groups, but not in the preRIC group. Plasma levels of NO, ADMA, TAC and
      H2S were not changed by ischemia and RIC. CONCLUSION: These results suggested
      that microvascular perfusion of human forearm skin was elevated by either
      endothelium or drug-derived NO. The effect of ischemia and RIC on NO-induced flow
      increase was affected differently by different applications in the healthy young
      individuals. These complicated results are taken into consideration in
      experimental and therapeutic interventions.

PMID- 29660912
TI  - Increased plasma viscosity in plasma cell dyscrasia and whole blood viscosity in
      polycythemia vera.
AB  - BACKGROUND: Although hyperviscosity syndrome in plasma cell dyscrasia (PCD) and
      thrombosis in myeloproliferative neoplasm (MPN) are major causes of morbidity and
      mortality, blood viscosity measurements are often underutilized. OBJECTIVE: This
      study aimed to characterize whether whole blood viscosity (WBV) or plasma
      viscosity (PV) could be predictive of hyperviscosity syndrome in PCD and could be
      elevated in subgroups of MPN. METHODS: A total of 75 patients with hematologic
      diseases: PCD (n = 26), MPN (n = 25) including polycythemia vera (P. vera) and
      lymphoma (n = 24) were enrolled along with 104 healthy controls. Both WBV and PV
      were measured using a capillary tube viscometer. Hyperviscosity syndrome was
      defined as having 2 or more hyperviscosity symptoms. RESULTS: Patients with PCD
      showed significantly higher PVs at high and low shear rates when compared to
      healthy controls, especially in those with hyperviscosity syndrome. The
      sensitivity and specificity of WBV and PV in detecting hyperviscosity syndrome
      were 28.6% and 94.1%, and 71.4% and 66.7%, respectively. Patients with P. vera
      exhibited high WBV and RBC counts compared to healthy controls. CONCLUSION: PV is
      predictive of hyperviscosity syndrome in PCD and WBV is elevated in patients with
      P. vera. It suggests that hemorheologic disturbances exist in patients with PCD
      and MPN and that tests of viscosity may be helpful in detecting hemorheological
      disturbances.

PMID- 29660913
TI  - GBT440 improves red blood cell deformability and reduces viscosity of sickle cell
      blood under deoxygenated conditions.
AB  - BACKGROUND: In sickle cell disease (SCD), polymerization of hemoglobin S (HbS)
      leads to the formation of rigid, non-deformable sickled RBCs. Loss of RBC
      deformability, sickling and irreversible membrane damage causes abnormal blood
      rheology, and increases viscosity which contributes to vasoocclusion and other
      SCD pathophysiology. GBT440 (generic name voxelotor) is a novel anti
      polymerization and anti-sickling agent currently undergoing clinical evaluation
      for the treatment of SCD. OBJECTIVE: The purpose of this study was to determine
      the effects of GBT440 on deformability of sickle RBCs (SS RBCs) and the
      hyperviscosity of sickle cell blood (SS blood). METHODS: The mechanical and
      rheological properties of GBT440-treated SS RBCs were measured using micropipette
      and filtration techniques. The viscosity of sickle blood was measured using a
      Wells-Brookfield cone/plate viscometer. RESULTS: GBT440 restored movement of
      deoxygenated SS RBCs through a gel filtration column and reduced the pressure
      required to pass SS RBCs through a polycarbonate filter. Moreover, GBT440
      decreased the membrane shear elastic modulus of SS RBCs assessed via micropipette
      aspiration and reduced the hyperviscosity of SS blood under deoxygenated
      conditions. CONCLUSIONS: GBT440 maintains SS RBC deformability and improves SS
      blood viscosity by inhibiting HbS polymerization under deoxygenated conditions.
      These results further support development of GBT440 as a disease-modifying agent
      in SCD patients.

PMID- 29660914
TI  - ShearWaveTM elastography for evaluation of the elasticity of Hashimoto's
      thyroiditis.
AB  - The aim of this study was to assess the elasticity of Hashimoto's thyroiditis in
      the different processes via supersonic ShearWaveTM Elastography (SWETM).
      Quantitative information is delivered as Young's modulus value expressed in kilo
      Pascal (kPa). 30 healthy female and 30 healthy male individuals aging at 40+/-20
      y had undergone conventional ultrasonography and SWE to determine the influence
      of gender on elasticity of thyroid. Also 60 female and 60 male patients (mean
      age, 40+/-20 y) with Hashimoto's thyroiditis in different processes underwent
      conventional ultrasonography and SWE to determine the elasticity of thyroid in
      Hashimoto's thyroiditis. Furthermore, the relationship between elasticity values
      and thyroid peroxidase antibody (TPOAB) in the patients was investigated. We
      found significant impact of gender on elasticity values of healthy thyroids. Our
      study showed that increased elasticity values with statistical significance in
      hyperthyroidism stage, normal thyroid function stage and hypothyroidism were
      shown. Low degree relationship between elasticity values and TPOAB was found in
      60 male patients. However, there was no such correlation in female patients.

PMID- 29660915
TI  - Hemorheological and metabolic consequences of renal ischemia-reperfusion and
      their modulation by N,N-dimethyl-tryptamine on a rat model.
AB  - BACKGROUND: Micro-rheological relations of renal ischemia-reperfusion (I/R) have
      not been completely elucidated yet. Concerning anti-inflammatory agents, it is
      supposed that sigma-1 receptor agonist N,N-dimethyl-tryptamin (DMT) can be useful
      to reduce I/R injury. OBJECTIVE: To investigate the micro-rheological and
      metabolic parameters, and the effects of DMT in renal I/R in rats. METHODS: In
      anesthetized rats from median laparotomy both kidneys were exposed. In Control
      group (n = 6) no other intervention happened. In I/R group (n = 10) the right
      renal vessels were ligated and after 60 minutes the organ was removed. The left
      renal vessels were clamped for 60 minutes followed by 120-minute reperfusion. In
      I/R+DMT group (n = 10) DMT was administered 15 minutes before the ischemia. Blood
      samples were taken before/after ischemia and during the reperfusion for testing
      hematological, metabolic parameters, erythrocyte deformability and aggregation.
      RESULTS: Lactate concentration significantly increased and accompanied with
      decreased blood pH. Enhanced erythrocyte aggregation and impaired deformability
      were observed from the 30th minute of reperfusion. In I/R+DMT group we found
      diminished changes compared to the I/R group (lactate, pH, electrolytes, red
      blood cell deformability and aggregation). CONCLUSIONS: Metabolic and micro
      rheological parameters impair during renal I/R. DMT could reduce but not
      completely prevent the changes in this rat model.

PMID- 29660916
TI  - Comparison of strain and acoustic radiation force impulse elastography of breast
      lesions by qualitative evaluation.
AB  - OBJECTIVES: To compare the diagnostic performance of conventional strain
      elastography (CSE) and acoustic radiation force impulse (ARFI) induced SE for
      qualitative assessment of breast lesions and evaluate the additional value of the
      two techniques combined with Breast Imaging Reporting and Data System (BI-RADS)
      respectively for the differentiation of benign and malignant breast lesions.
      METHODS: In a cohort of 110 women, the conventional ultrasound (US) features and
      the elasticity scores of CSE and ARFI induced SE were recorded. The diagnostic
      performances of BI-RADS, elastography and BI-RADS plus elastography were
      evaluated, including the area under the receiver operating characteristic curve
      (AUROC), sensitivity, specificity and accuracy. RESULTS: Pathologically, there
      were forty-eight malignant and sixty-two benign breast lesions in the final
      analysis. The AUCs for CSE and ARFI induced SE are similar (CSE, 0.807; ARFI
      induced SE, 0.846; p > 0.05), however, the specificity of the latter method was
      significantly higher than that of CSE (83.9% vs. 58.1%, p = 0.004) in
      differentiating breast lesions. The accuracy and specificity of BI-RADS plus ARFI
      induced SE (84.5%, 80.6%, respectively) were significantly higher than BI-RADS
      alone (73.6%, 54.8%, respectively) and BI-RADS plus conventional SE (72.7%,
      56.5%, respectively), respectively (p < 0.05) without loss of sensitivity.
      CONCLUSIONS: Our study showed that BI-RADS plus ARFI induced SE had a better
      diagnostic performance in the diagnosis of breast lesions in comparison with BI
      RADS alone or BI-RADS plus CSE.

PMID- 29660917
TI  - Medical compression stockings reduce hypertension of nailfold capillaries at the
      toe of patients with chronic venous insufficiency1.
AB  - : In five patients who suffered from chronic venous insufficiency clinical stage
      C4 (n = 3) and C6 (n = 2) the capillary blood pressure was measured twice by
      means of invasive direct cannulation of nailfold capillaries of the toe. During
      one measurement course the patients wore below knee medical compression stockings
      (40 mmHg) during the other they did not have compression therapy. With the
      patient in supine position, the CP was investigated by the servo-nulling
      technique under resting conditions and under dynamic conditions: the calf
      muscle/ankle joint venous pump was simulated by means of inflating a blood
      pressure cuff, which surrounded the mid lower leg, to 60 mmHg for 60 s. RESULTS:
      The simulated calf-muscle contraction induced a steep increase of CP with 5.65
      mmHg/s (Q1 5.27 mmHg/s, Q3 5.92 mmHg/s), which was significantly (p = 0.013)
      reduced by MCS to 2.47 mmHg/s (Q1 1.65 mmHg/s, Q3 3.0 mmHg/s). Time needed to
      reach the max. CP was 11.35 s, which was lengthened by MCS to 23.4 s (p = 0.134).
      CONCLUSION: Compression therapy prevents capillary hypertension, the major
      hemodynamic reason for the development of advanced stages of chronic venous
      insufficiency which are defined by skin disease like hyperpigmentation,
      lipodermatosclerosis and ulcer.

PMID- 29660918
TI  - Contrast enhanced ultrasound (CEUS) with MRI image fusion for monitoring focal
      therapy of prostate cancer with high intensity focused ultrasound (HIFU)1.
AB  - INTRODUCTION: Reduced acceptance of radical prostatectomy in patients with low
      risk or intermediate risk prostate cancer has significantly changed treatment
      strategies in prostate cancer (PCa) during the last years. Focal therapy of the
      prostate with high intensity focused ultrasound (HIFU) is an organ-preserving
      treatment for prostate cancer with less impairment of health-related quality of
      life. Follow-up after HIFU therapy by imaging modalities remains a major problem
      as eg. MRI performs poorly. Contrast enhanced ultrasound (CEUS) allows to monitor
      the vascular architecture of organs non-invasively. However, only limited data
      are available using CEUS to define successful and complete HIFU treatment of the
      prostate. In this study, we aimed to evaluate short-term image findings using
      CEUS and image fusion before and after HIFU treatment. MATERIALS AND METHODS:
      Prospective single arm study in patients with uni- or bilateral, low or
      intermediate risk prostate cancer or recurrent cancer after radiotherapy treated
      with HIFU at our institution between October 2016 and November 2017. HIFU
      hemiablation or whole gland treatment was performed using the Focal One(r)
      device. PCa was diagnosed either by multiparametric magnetic resonance imaging
      (mpMRI) followed by MRI fusion based targeted biopsy combined with 12 core
      transrectal ultrasound (TRUS) guided biopsy or 12 core random biopsy only.
      Monitoring of the target region before, immediately and 24 hours after the
      ablation was done by CEUS in combination with image fusion using an axial T2
      weighted MRI sequence. RESULTS: 6 consecutive patients with Gleason score (GS) 6,
      5 patients with GS 7a prostate cancer and one patient with biochemical recurrence
      after radiotherapy were included in the study. Three patients underwent whole
      gland treatment due to histological proven bilateral PCa or recurrent PCa after
      radiotherapy. Hemiablation was performed in 9 patients with unilateral tumor and
      no PIRADS 4 or 5 lesion in the contralateral lobe. Median patient age was 69.8
      years and median PSA (prostate-specific antigen) level was 8.4 ng/ml. CEUS showed
      markedly reduced microbubbles in the ablated area, the prostate capsule still
      showed signs of perfusion. The study is limited by the short follow up and small
      number of patients. CONCLUSIONS: CEUS examination showed a reduction of
      microcirculation in the treated area immediately after the treatment and 24 hours
      later. The combination of CEUS and image fusion seems to be helpful for detecting
      the PCa target lesion and monitor the success of HIFU ablation treatment.
      Evidence for image findings after HIFU-therapy are rare. Further studies on this
      topic are needed.

PMID- 29660919
TI  - Blood rheology as a mirror of endocrine and metabolic homeostasis in health and
      disease1.
AB  - Rheological properties of plasma and blood cells are markedly influenced by the
      surrounding milieu: physicochemical factors, metabolism and hormones. Acid/base
      status, osmolality, lipid status, plasma protein pattern, oxidative stress
      induced by increased free radicals production, endothelium-derived factors such
      as nitric oxide (NO), achidonic acid derivatives modulate both red blood cell
      (RBC) and white cell mechanics. Therefore, regulatory axes involving liver,
      endothelium, kidney, pancreas, adrenal gland, endocrine heart, adipose tissue,
      pituitary gland, and surely other tissues play important roles in the regulation
      of blood fluidity. A comprehensive picture of all this complex network of
      regulatory loops is still unavailable but current progress of knowledge suggest
      that some attempts can currently be made.

PMID- 29660920
TI  - Evidence for cytostatic effect of cyclophosphamide on human vein endothelial
      cells in cancer therapy: Preliminary in vitro results.
AB  - In cancer therapy, a number of drugs with different mechanisms of action are in
      clinical use, which act directly after administration without metabolism, while
      others only become active in the metabolites produced in the liver. Such
      drugs/metabolites - especially when administered parenterally - interact in high
      concentrations with the endothelium. Whether this induces adverse responses of
      the endothelial cells (EC) is barely studied for many medicaments.This pilot in
      vitro study revealed that the addition of cyclophosphamide (CPA) to the culture
      medium (5 or 10 mM, respectively) showed a clear influence on EC compared to non
      treated EC: The number of adherent human vein endothelial cells (HUVEC) decreased
      by the addition of CPA in a concentration-dependent manner compared to the
      untreated control, whereby the vitality of adherent cells was not affected. In
      addition, concomitant with activation of the adherent HUVEC, increased migratory
      activity occurred.These results are in agreement with clinical events like
      thromboses in patients in compromised condition under therapy with CPA, as the
      detachment of EC might induce responses of circulating platelets leading to the
      adherence and aggregation with the risk of the formation of thrombi. Whether CPA
      acts directly or via toxic metabolites on EC will be examined in more detail in
      following studies.

PMID- 29660921
TI  - Extract of Oxytropis pseudoglandulosa inhibits vascular smooth muscle cell
      proliferation and migration via suppression of ERK1/2 and Akt signaling
      pathways1.
AB  - Excessive vascular smooth muscle cell (VSMC) proliferation and migration
      accelerate the development of occlusive vascular disease. Therefore, finding a
      means to control the aberrant proliferation and migration of VSMCs has own
      clinical significance. In the present study, we examined the feasibility of using
      extract from medicinal plant Oxytropis pseudoglandulosa (OG) to control
      pathologic proliferation and migration of VSMCs, which never have been tested.
      Our data indicate that the extract of OG significantly suppressed proliferation
      and migration of VSMCs without cytotoxic effect, suggesting the OG extract may be
      an alternative agent to effectively control the aberrant VSMC proliferation and
      migration without any serious adverse effect. These data suggest that the extract
      of OG may be a potent therapeutic agent for the treatment of occlusive vascular
      disease and warrant further studies to identify the major acting ingredient and
      to validate in vivo efficacy.

PMID- 29660922
TI  - Triglycerides as indicators of erythrocyte hemoglobin oxygen-binding properties1.
AB  - OBJECTIVES: To assess the relationships of clinical and laboratory parameters,
      with erythrocyte oxygen concentration. METHODS: The study group consisted of 47
      healthy adults out of which 16 showed slightly higher blood pressure and were
      classified as individuals with prehypertension. For each individual, data were
      obtained on: systolic and diastolic blood pressure (SBP, DBP), blood morphology,
      lipids profile, fibrinogen, hs-CRP. The erythrocyte oxygen concentration was
      assessed with the Raman spectroscopy technique. Arithmetic means for all
      laboratory parameters were estimated by oxygen concentration tertiles and tested
      for statistical significance of linear trends across tertiles. RESULTS: The
      multivariate regression analysis showed statistically significant negative
      relationship of triglycerides level with oxygen concentration. CONCLUSIONS: A
      hypothesis has been formulated that triglycerides level is an indicator of the
      erythrocyte ability to transport oxygen to the tissues.

PMID- 29660923
TI  - Haemochromatosis: Pathophysiology and the red blood cell1.
AB  - Haemochromatosis remains the most prevalent genetic disorder of Caucasian
      populations in Australia and the United States, occurring in ~1 of 200
      individuals and having a carrier frequency of 10-14%. Hereditary haemochromatosis
      is an autosomal recessive condition, that is phenotypically characterised by a
      gradual accumulation of iron, above and beyond that required for biological
      function. Once the binding capacity of iron carriers reaches saturation, the
      highly reactive free iron generates radicals that may lead to widespread cellular
      dysfunction. Thus, the compounding effects of systemic iron overload and the
      associated oxidative stress in untreated haemochromatosis patients results in
      tissue damage precipitating severe complications, including: liver cirrhosis,
      hepatocellular cancer, cardiomyopathy, and diabetes. The primary treatment
      indicated for individuals with haemochromatosis is venesection therapy (i.e.,
      regular bloodletting of ~450 mL). Given the frequency of venesection required to
      decrease and normalise the elevated iron levels, this population may serve as a
      valuable source of blood products which are in short supply. While the
      complications associated with elevated iron deposits are frequently reported, the
      influence of haemochromatosis on the rheological properties of blood and red
      blood cells (RBC) - major determinants of microvascular blood flow and tissue
      perfusion - are poorly understood. Limited studies investigating haemorheology in
      patients with haemochromatosis have reported altered physical properties of
      blood, which may partly explain the comorbidities associated with the disorder.
      The current review will explore the aetiology, pathology, and clinical
      implications of haemochromatosis disease and the associated oxidative stress,
      with particular emphasis on RBC.

PMID- 29660924
TI  - Vasopressor support vs. liberal fluid administration in deep inferior epigastric
      perforator (DIEP) free flap breast reconstruction - a randomized controlled
      trial.
AB  - BACKGROUND: Perioperatively, patients' hemodynamics are modulated predominantly
      by intravenous fluid administration and vasoactive pharmacological support.
      Vasopressor agents are suspected to be detrimental on free flap survival by the
      cause of vasoconstriction of the pedicle with consecutive reduced overall flap
      perfusion and by aggravation of flap dissection. OBJECTIVE: A novel, standardized
      fluid restrictive perioperative hemodynamic management was assessed for its
      feasibility in clinical practice in free flap patients undergoing breast
      reconstruction. METHODS: Patients were randomized to two perioperative regimens
      with different fluid and vasopressor limits. The primary endpoint regarded flap
      survival. Secondary endpoints included surgery times, time of patient ambulation
      and length of hospital stay. RESULTS: There was one total flap failure with
      liberal fluid administration (LFA). No total or partial flap failure was noted in
      the fluid restrictive regimen with norepinephrine administration up to
      0.04MUg/kg/min (FRV). No delay regarding operation time (p = 0.217), patient
      mobilization (p = 0.550) or hospital discharge (p = 0.662) was registered in the
      FRV study subpopulation compared to LFA. CONCLUSIONS: The results of this
      prospective interventional trial could not detect any negative impact of
      vasopressors, neither for the primary endpoint of flap survival nor for the
      overall patient outcome. The fear of vasopressor associated flap complications
      has led to a traditional liberal fluid administration, which failed to
      demonstrate any benefits when compared to a fluid restrictive vasopressor
      strategy.

PMID- 29660925
TI  - Influence of different surface treatments of poly(n-butyl acrylate) networks on
      fibroblasts adhesion, morphology and viability.
AB  - BACKGROUND: Physical and chemical characteristics of implant materials determine
      the fate of long-term cardiovascular devices. However, there is still a lack of
      fundamental understanding of the molecular mechanisms occurring in the material
      tissue interphase. In a previous study, soft covalently crosslinked poly(n-butyl
      acrylate) networks (cPnBA) were introduced as sterilizable, non-toxic and immuno
      compatible biomaterials with mechanical properties adjustable to blood vessels.
      Here we study the influence of different surface treatments in particular oxygen
      plasma modification and fibrinogen deposition as well as a combinatorial approach
      on the adhesion and viability of fibroblasts. MATERIAL AND METHODS: Two types of
      cPnBA networks with Young's moduli of 0.19+/-0.01 MPa (cPnBA04) and 1.02+/-0.01
      MPa (cPnBA73) were synthesized and post-modified using oxygen plasma treatment
      (OPT) or fibrinogen coating (FIB) or a combination of both (OPT+FIB). The water
      contact angles of the differently post-treated cPnBAs were studied to monitor
      changes in the wettability of the polymer surfaces. Because of the key role of
      vascular fibroblasts in regeneration processes around implant materials, here we
      selected L929 fibroblasts as model cell type to explore morphology, viability,
      metabolic activity, cell membrane integrity as well as characteristics of the
      focal adhesions and cell cytoskeleton on the cPnBA surfaces. RESULTS: Compared to
      non-treated cPnBAs the advancing water-contact angles were found to be reduced
      after all surface modifications (p < 0.05, each), while lowest values were
      observed after the combined surface treatment (OPT+FIB). The latter differed
      significantly from the single OPT and FIB. The number of adherent fibroblasts and
      their adherence behavior differed on both pristine cPnBA networks. The fibroblast
      density on cPnBA04 was 743+/-434 cells.mm-2, was about 6.5 times higher than on
      cPnBA73 with 115+/-73 cells.mm-2. On cPnBA04 about 20% of the cells were visible
      as very small, round and buckled cells while all other cells were in a migrating
      status. On cPnBA73, nearly 50% of fibroblasts were visible as very small, round
      and buckled cells. The surface functionalization either using oxygen plasma
      treatment or fibrinogen coating led to a significant increase of adherent
      fibroblasts, particularly the combination of both techniques, for both cPnBA
      networks. It is noteworthy to mention that the fibrinogen coating overruled the
      characteristics of the pristine surfaces; here, the fibroblast densities after
      seeding were identical for both cPnBA networks. Thus, the binding rather depended
      on the fibrinogen coating than on the substrate characteristics anymore. While
      the integrity of the fibroblasts membrane was comparable for both polymers, the
      MTS tests showed a decreased metabolic activity of the fibroblasts on cPnBA.
      CONCLUSION: The applied surface treatments of cPnBA successfully improved the
      adhesion of viable fibroblasts. Under resting conditions as well as after
      shearing the highest fibroblast densities were found on surfaces with combined
      post-treatment.

PMID- 29660926
TI  - Abnormal rheological properties of red blood cells as a potential marker of Gulf
      War Illness: A preliminary study.
AB  - BACKGROUND: Veterans with Gulf War Illness (GWI) experience chronic symptoms that
      include fatigue, pain, and cognitive impairment. This symptom cluster may be the
      consequence of impaired tissue oxygen delivery due to red blood cell (RBC)
      dysfunction. OBJECTIVE: The purpose of this preliminary study was to determine
      whether the microrheological behavior of RBCs is altered in GWI. METHODS: We
      recruited 17 cases of GWI (GWI+) and 10 age matched controls (GWI-), and examined
      RBC deformability and aggregation via ektacytometry along with measurement of
      complete blood counts. RESULTS: RBCs were more deformable in GWI+, as indicated
      by higher elongation indices particularly at higher shear stress values (5.33,
      9.49, and 16.89) when compared to GWI-. Aggregation formation, stability and
      kinetics were similar between GWI+and GWI-. Complete blood counts were also
      similar, with the exception of mean corpuscular hemoglobin (MCH), mean
      corpuscular hemoglobin concentration (MCHC), and RBC distribution width (RDW)
      which was elevated in GWI+. CONCLUSIONS: In this preliminary study, we observed
      increased deformability along with increased MCH, MCHC and RDW in veterans with
      GWI+, which may contribute to the symptomatology of GWI. Further research is
      required to confirm our findings and the role of RBC microrheology in GWI.

PMID- 29660927
TI  - An explanation of the reversal of erythrocyte echinocytosis by incubation and
      storage by serum albumin.
AB  - It is proposed that the specific reversal by serum albumin of the erythrocyte
      echinocytosis in an inorganic phosphate buffer saline or in a saline, either
      after 24 h in blood or after a storage of 6-7 weeks in SGAM or PAGGSM media, is
      due to a cell dehydration by a decrease of the total NaCl and KCl concentrations
      favoring the stomatocytogenic slow outward transport of inorganic phosphate with
      a hydrogen ion by band 3 anion exchanger, which was previously proposed to
      control the erythrocyte shape. This proposal would indicate that the opposition
      of the erythrocyte echinocytosis by serum albumin is not limited to binding to
      echinocytogenic amphiphiles, supported by the ability of the band 3-based
      mechanism of control of the erythrocyte shape to explain a variety of
      observations on the erythrocyte shape. It would also imply that this mechanism is
      a determinant of the erythrocyte rheological properties since influenced by cell
      shape and volume. It is shown that the above process of stomatocytosis can
      explain stomatocytoses by different agents as well as a knizocytosis induced in
      vitro and occurring in acquired and inherited disorders and other situations.
      Lastly, it can also explain the opposition of hemolysis by mannitol in SGAM and
      PAGGSM media.

PMID- 29660928
TI  - Adrenal schwannoma: CT, MR manifestations and pathological correlation.
AB  - OBJECTIVES: This study aimed to describe the computed tomography (CT), magnetic
      resonance imaging (MRI) imaging features of adrenal schwannoma and to correlate
      imaging findings with histopathologic findings. METHODS: The findings from
      multiphase CT or MRI examinations of seventeen patients with histopathologically
      confirmed adrenal schwannoma were reviewed. The imaging criteria included shape,
      size, margin, attenuation, signal intensity, secondary degeneration, and internal
      mass enhancement pattern. RESULTS: All cases were unilateral, round or oval
      solitary tumors, with diameters ranging from approximately 2.5 to 8.8 cm (median
      = 4.5 cm). Of the twelve cases assessed using CT, adrenal schwannoma appeared as
      well-circumscribed round or oval low-density suprarenal masses with a mean
      attenuation values of 30.1 HU of solid portions during unenhanced phase. Ten
      cases exhibited heterogeneous cyst formation, and one case showed calcification.
      Internal septa were noted in 5 cases. All solid areas displayed early mild
      heterogeneous enhancement and delayed progressive enhancement. Regarding MRI,
      solid portions of five masses were hypointense to the liver parenchyma on T1
      weighted imaging (T1WI) and were heterogeneously hyperintense on T2-weighted
      imaging (T2WI). The enhanced pattern of solid areas of adrenal schwannoma on MRI
      is similar to that of CT. Cystic or hemorrhagic changes were noted in 4 cases and
      internal septa were noted in 3 cases. CONCLUSION: Although schwannoma is a rare
      entity in the adrenal gland, we believe that the following signs may suggest the
      diagnosis of this entity: a non-lipid containing mass, a well-defined border, a
      unilateral mass with cystic or hemorrhagic degeneration, septa with delayed
      enhancement and a characteristic progressive contrast enhancement pattern of the
      solid portions.

PMID- 29660929
TI  - Ecchymosis: A novel sign in patients with varicose veins.
AB  - BACKGROUND: In the absence of trauma, hematologic disease and anti-platelet use,
      no attention has been paid to elucidate the mechanism of ecchymosis. It has taken
      our attention that ecchymosis on lower limb might be a sign of varicose vein.
      Accordingly, we aimed to analyze and describe the frequency of leg symptoms and
      presence of ecchymosis in patients with varicose vein. MATERIALS AND METHODS:
      Four hundred and ninety four patients who had been diagnosed as having varicose
      vein or chronic venous insufficiency either by clinical examination or Doppler
      ultrasonography were included in the study. Leg symptoms were defined as pain,
      itching, muscle cramps, throbbing, and swelling. Ulcers, pigmentations and
      ecchymosis were recorded as signs of varicose vein. Ecchymosis was defined as a
      hemorrhagic lesions, larger than >3 mm on the skin of lower extremities, forming
      a flat, rounded or irregular, blue or purplish patch. RESULTS: Leg pain was the
      most common symptom in our study population. Ecchymosis was observed in 24
      patients (5%). Logistic regression analysis showed that ecchymosis was
      significantly and positively associated with muscle cramps (Odds ratio: 5.82, p =
      0.001) and female gender (Odds ratio: 5.17 p = 0,019 but negatively associated
      with age (Odds ratio: 0.94, p = 0.004). CONCLUSION: We have documented for the
      first time that the frequency of ecchymosis and its association with muscle
      cramps in a relatively large patient population with peripheral varicose vein or
      chronic venous insufficiency. Ecchymosis on lower limbs should be considered as a
      novel sign of varicose vein.

PMID- 29660930
TI  - A.L. Copley Best Paper Prize 2017.

PMID- 29660931
TI  - In memory of Prof. Dr. Sandro Forconi.

PMID- 29660932
TI  - Neuroprotective Effects of Ferruginol, Jatrophone, and Junicedric Acid Against
      Amyloid-beta Injury in Hippocampal Neurons.
AB  - Soluble amyloid-beta (Abeta) oligomers have been recognized as early neurotoxic
      intermediates with a key role in the synaptic dysfunction observed in Alzheimer's
      disease (AD). Abeta oligomers block hippocampal long-term potentiation (LTP) and
      impair rodent spatial memory. Additionally, the presence of Abeta oligomers is
      associated with imbalanced intracellular calcium levels and apoptosis in neurons.
      In this context, we evaluated the effects of three diterpenes (ferruginol,
      jatrophone, and junicedric acid) that are found in medicinal plants and have
      several forms of biological activity. The intracellular calcium levels in
      hippocampal neurons increased in the presence of ferruginol, jatrophone, and
      junicedric acid, a result that was consistent with the observed increase in CA1
      synaptic transmission in mouse hippocampal slices. Additionally, assays using
      Abeta peptide demonstrated that diterpenes, particularly ferruginol, restore LTP
      and reduce apoptosis. Recovery of the Abeta oligomer-induced loss of the synaptic
      proteins PSD-95, synapsin, VGlut, and NMDA receptor subunit 2A was observed in
      mouse hippocampal slices treated with junicedric acid. This cascade of events may
      be associated with the regulation of kinases, e.g., protein kinase C (PKC) and
      calcium/calmodulin-dependent protein kinase II (CaMKII), in addition to the
      activation of the canonical Wnt signaling pathway and could thus provide
      protection against Abeta oligomers, which trigger synaptic dysfunction. Our
      results suggest a potential neuroprotective role for diterpenes against the Abeta
      oligomers-induced neurodegenerative alterations, which make them interesting
      molecules to be further studied in the context of AD.

PMID- 29660933
TI  - Medical Comorbidity in Alzheimer's Disease: A Nested Case-Control Study.
AB  - BACKGROUND: Little is known about the distribution of medical comorbidities in
      Alzheimer's disease (AD). OBJECTIVE: We aimed to describe the comorbidity pattern
      of AD in a nested case-control study. METHODS: Incident AD cases were identified
      by International Classification of Diseases codes in a random sample of 2 million
      individuals in Taiwan National Health Insurance program during 2001-2011. We
      further restricted cases to those treated with AD drugs of approved
      reimbursement. We sampled a set of age- and sex-matched control subjects (2:1
      ratio) and employed conditional logistic regression to estimate the associations
      between pre-specified 14 comorbidities and AD. The clusters of multiple chronic
      diseases were then identified by exploratory factor analysis. RESULTS: A total of
      2,618 AD cases were identified during 2001-2011 with a mean age of 76.1 years and
      female preponderance (59%). The most common 5 comorbidities in AD were
      hypertension (55.1%), osteoarthritis (38.2%), depression (32.3%), diabetes
      mellitus (DM) (25.7%), and cerebrovascular disease (CVD) (22.7%). After adjusting
      for age and sex, DM, osteoporosis, depression, and CVD were significantly
      associated with AD. The number of comorbidity was 3-fold greater in the AD group.
      The cluster of hypertension, DM, and hyperlipidemia was the most common
      combination in old age, whereas the cluster osteoarthritis and osteoporosis was
      the only multimorbidity pattern significantly associated with AD. CONCLUSION:
      Multimorbidity is common in AD. Depression, CVD, osteoporosis, and DM are
      associated with incident AD, supporting that their co-existence is a typical
      feature of AD at old age. Comorbidity care should be integrated into current
      management for patients with AD.

PMID- 29660935
TI  - Effect of Cilostazol on Incident Dementia in Elderly Men and Women with Ischemic
      Heart Disease.
AB  - BACKGROUND: Ischemic heart disease (IHD) is associated with cognitive decline and
      may contribute to an increased risk of dementia. OBJECTIVE: The goal of the
      present study was to investigate whether cilostazol use is associated with a
      lower risk of incident dementia in Asian patients with IHD, and whether these
      effects differed based on sex. METHODS: This retrospective cohort study was
      performed using the Korean National Insurance Claim Data of the Health Insurance
      Review and Assessment Service; the duration of the study was from January 1, 2007
      to December 31, 2015. The study group comprised 66,225 patients with IHD, aged
      >65 years, who had received cilostazol. Age- and sex-matched IHD patients without
      cilostazol exposure were selected as the control group. The risk of dementia was
      compared between the cilostazol and control groups. RESULTS: Compared to the
      control group, total cilostazol users had a marginally significant lower risk of
      incident dementia. After stratification by sex, the reducing effect of cilostazol
      on incident dementia was significant in female participants, but not in male
      participants. Female patients who had cilostazol for over 2 years showed a
      clinically meaningful preventive effect (HR, 0.85; 95% CI, 0.82-0.88).
      CONCLUSIONS: This study suggested that cilostazol treatment may reduce the risk
      of incident dementia in Korean patients with IHD. Its beneficial effect was
      remarkably significant in female patients who received cilostazol for over a 2
      year period.

PMID- 29660934
TI  - Bi-directional Association of Cerebrospinal Fluid Immune Markers with Stage of
      Alzheimer's Disease Pathogenesis.
AB  - Immune mechanisms may be important in the pathogenesis of Alzheimer's disease
      (AD). Yet, studies comparing cerebrospinal fluid (CSF) and plasma immune marker
      levels of healthy and demented individuals have yielded conflicting results. We
      analyzed CSF from 101 members of the parental history-positive PREVENT-AD cohort
      of healthy aging adults, and 237 participants without dementia from the initial
      cohort of the Alzheimer's Disease Neuroimaging Initiative (ADNI-1). Following
      recent practice, we used the biomarkers total-tau and amyloid-beta1-42 to
      allocate participants from each study into four stages of AD pathogenesis: Stage
      0 (no abnormality), Stage 1 (reduced amyloid-beta1-42), Stage 2 (reduced amyloid
      beta1-42 and increased total-tau), or "Suspected Non-Alzheimer Pathology"
      (elevated total-tau only). Investigating the PREVENT-AD participants' CSF assay
      results for 19 immune/inflammatory markers, we found six that showed a distinct
      bi-directional relationship with pathogenetic stage. Relative to Stage 0, these
      were diminished at Stage 1 but strongly increased at Stage 2. Among the ADNI
      participants (90 healthy controls and 147 with mild cognitive impairment), we
      found that 23 of 83 available CSF markers also showed this distinct pattern.
      These results support recent observations that immune activation may become
      apparent only after the onset of both amyloid and tau pathologies. Unexpectedly,
      they also suggest that immune marker activity may diminish along with earliest
      appearance of amyloid-beta plaque pathology. These findings may explain
      discordant results from past studies, and suggest the importance of
      characterizing the extent of AD pathology when comparing clinical groups.

PMID- 29660936
TI  - Associations of Angiotensin Converting Enzyme-1 and Angiotensin II Blood Levels
      and Cognitive Function.
AB  - BACKGROUND: Emerging evidence suggests a possible role of the renin angiotensin
      system in the pathophysiologic process of Alzheimer's disease, of which
      angiotensin converting enzyme-1 (ACE-1) and angiotensin II (ANGII) are important
      proteins. Few studies evaluated associations between blood ACE-1 and none between
      ANGII levels, and cognition. OBJECTIVE: Our pilot study was aimed to examine
      associations between blood ACE-1 and ANG II levels and cognitive function in non
      demented participants at baseline and over a 1-year period. METHODS: 56
      participants were included from the Brain Health Substudy of the Baltimore
      Experience Corps Study. Linear regression analysis, adjusting for confounders,
      was used to determine associations between baseline ACE-1 and ANGII, and baseline
      and 1-year follow-up measures of psychomotor and processing speed, executive
      function, verbal learning memory and working memory, and whether these
      associations were mediated by blood pressure. RESULTS: Participants were
      predominantly female (75%), African-American (93%), with mean age of 67.8 years
      and education of 14.3 years. There were no associations between baseline ACE-1 or
      ANGII levels and cognitive function; however, there were significant association
      between baseline ACE-1 levels and 1-year follow-up Trail Making Test, Part A
      (beta= 0.003, p = 0.04) and Digit Span (beta= -0.001, p = 0.02). CONCLUSIONS: In
      this cognitively intact sample, elevated ACE-1 levels were associated with worse
      processing speed and working memory after 1 year. Findings from this pilot study
      suggest that changes in the RAS are associated with alterations in cognitive
      function warranting further assessment of the role of RAS in neurodegenerative
      disorders.

PMID- 29660937
TI  - Personality Modulates the Efficacy of Art Intervention on Chronic Pain in a
      Population of Patients with Alzheimer's Disease.
AB  - BACKGROUND: Alzheimer's disease (AD) mainly occurs in elderly individuals.
      Comorbidities and chronic pain are frequent in this population. Previous studies
      revealed that personality modulates both chronic pain (CP) andADoccurrence and
      evolution. Moreover, as pain treatments can induce side-effects, non-drugs
      treatments, such as art interventions, are interesting alternative therapies for
      decreasing CP in these patients. OBJECTIVE: Our aim was to assess the potential
      role of personality traits on art intervention efficacy for reducing CP in a
      population of patients with mild AD. METHODS: Design: multicenter randomized
      controlled trial. Fifty mild AD patients underwent a 12-week art intervention
      including singing and painting groups. Personality was assessed with the Big Five
      Inventory before the sessions. CP was measured with Numeric Rating Scale (NRS)
      [Usual pain (NRS-U) and most Intense pain (NRS-I)], Simple Visual Scale [Usual
      pain (SVS-U) and most Intense pain (SVS-I)] and Brief Pain Inventory (BPI) before
      and after the sessions. The influence of personality traits on CP evolution
      before and after art intervention was assessed with multiple linear regression
      models. RESULTS: A positive association was observed between neuroticism and the
      evolution of three CP measures including NRS-U (B = 0.34, p = 0.01), SVS-U (B =
      0.20, p = 0.04), and BPI-U (B = 0.46, p = 0.02) evolution. No significant
      relationship was observed between neuroticism and NRS-I, SVS-I and BPI-R
      evolution. CONCLUSIONS: Our findings suggest that neuroticism can decrease the
      efficacy of group art intervention on pain in patients with mild AD. Individual
      therapies could be more appropriate for these patients. These results emphasize
      the interest of taking into account patients' personality before proposing them
      to participate to a group therapy.

PMID- 29660939
TI  - Aberrant Cortical Event-Related Potentials During Associative Learning in Rat
      Models for Presymptomatic Stages of Alzheimer's Disease.
AB  - Trace eyeblink conditioning is a hippocampus-dependent associative learning
      paradigm which is impaired in patients with Alzheimer's disease (AD) and animal
      AD models. Learning in this paradigm accompanies changes in oscillatory activity
      in forebrain regions, some of which are loci of pathogenic changes in prodromal
      AD stages. These observations motivated us to examine how cortical event-related
      potentials (ERPs) during this paradigm are affected by two features of the
      asymptomatic, AD-related brain abnormality, entorhinal tau accumulation and mild
      cholinergic deficit. Adult rats received viral overexpression of P301L mutant
      human tau in the entorhinal cortex, low-dose scopolamine treatment, or both.
      Electroencephalograms were recorded with epidural electrodes on the surface of
      the frontal, parietal, and temporal cortices during differential and reversal
      trace eyeblink conditioning. All rats developed conditioned responses to one of
      two stimuli (auditory or visual) paired with mild eyelid shock (CS+), but not to
      the other stimulus presented alone (CS-). They were also able to adjust the
      response when the stimulus contingency was reversed. With learning, the amplitude
      of several ERP components in the frontal and temporal cortices came to
      differentiate the CS+ from CS-. Scopolamine affected the learning-related change
      in temporal P2 and other learning-unrelated components in three regions.
      Entorhinal tau overexpression primary affected the amplitude of temporal visual
      ERPs and learning-unrelated frontal and temporal auditory ERP components. The
      double manipulation only affected two components of temporal auditory ERPs. Thus,
      cortical ERPs during differential associative learning are sensitive to
      asymptomatic brain abnormality associated with AD.

PMID- 29660940
TI  - Age-Dependent Changes to Sphingolipid Balance in the Human Hippocampus are Gender
      Specific and May Sensitize to Neurodegeneration.
AB  - The greatest risk factor for developing Alzheimer's disease (AD) is aging. The
      major genetic risk factor for AD is the E4 allele of the APOE gene, encoding the
      brain's major lipid transport protein, apolipoprotein E (ApoE). The research
      community is yet to decipher why the ApoE4 variant pre-disposes to AD, and how
      aging causes the disease. Studies have shown deregulated levels of sphingolipids,
      including decreased levels of the neuroprotective signaling lipid sphingosine 1
      phosphate (S1P), and increased ceramide content, in brain tissue and serum of
      people with pre-clinical or very early AD. In this study we investigated whether
      sphingolipid levels are affected as a function of age or APOE genotype, in the
      hippocampus of neurologically normal subjects over the age of 65. Lipids were
      quantified in 80 postmortem tissue samples using liquid chromatography tandem
      mass spectrometry (LC-MS/MS). Sphingolipid levels were not significantly affected
      by the presence of one E4 or E2 allele. However, ceramide, sphingomyelin, and
      sulfatide content was very significantly correlated with age in the hippocampus
      of males. On the other hand, S1P, normalized to its non-phosphorylated precursor
      sphingosine, was inversely correlated with age in females. Our results therefore
      establish gender-specific differences in sphingolipid metabolism in the aging
      human brain. Ceramide is a pro-apoptotic lipid, and heavily implicated as a
      driver of insulin resistance in metabolic tissues. S1P is a neuroprotective lipid
      that supports glutamatergic neurotransmission. Increasing ceramide and decreasing
      S1P levels may contribute significantly to a pro-neurodegenerative phenotype in
      the aging brain.

PMID- 29660938
TI  - The Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog):
      Modifications and Responsiveness in Pre-Dementia Populations. A Narrative Review.
AB  - The Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) was
      developed in the 1980s to assess the level of cognitive dysfunction in
      Alzheimer's disease. Advancements in the research field have shifted focus toward
      pre-dementia populations, and use of the ADAS-Cog has extended into these pre
      dementia studies despite concerns about its ability to detect important changes
      at these milder stages of disease progression. If the ADAS-Cog cannot detect
      important changes, our understanding of pre-dementia disease progression may be
      compromised and trials may incorrectly conclude that a novel treatment approach
      is not beneficial. The purpose of this review was to assess the performance of
      the ADAS-Cog in pre-dementia populations, and to review all modifications that
      have been made to the ADAS-Cog to improve its measurement performance in dementia
      or pre-dementia populations. The contents of this review are based on
      bibliographic searches of electronic databases to locate all studies using the
      ADAS-Cog in pre-dementia samples or subsamples, and to locate all modified
      versions. Citations from relevant articles were also consulted. Overall, our
      results suggest the original ADAS-Cog is not an optimal outcome measure for pre
      dementia studies; however, given the prominence of the ADAS-Cog, care must be
      taken when considering the use of alternative outcome measures. Thirty-one
      modified versions of the ADAS-Cog were found. Modification approaches that appear
      most beneficial include altering scoring methodology or adding tests of memory,
      executive function, and/or daily functioning. Although modifications improve the
      performance of the ADAS-Cog, this is at the cost of introducing heterogeneity
      that may limit between-study comparison.

PMID- 29660941
TI  - Brimapitide Reduced Neuronal Stress Markers and Cognitive Deficits in 5XFAD
      Transgenic Mice.
AB  - Alzheimer's disease (AD) is characterized by accumulations of amyloid-beta
      (Abeta42) and hyperphosphorylated tau proteins, associated with
      neuroinflammation, synaptic loss, and neuronal death. Several studies indicate
      that c-Jun N-terminal kinase (JNK) is implicated in the pathological features of
      AD. We have investigated in 5XFAD mice, the therapeutic effects of Brimapitide, a
      JNK-specific inhibitory peptide previously tested with higher concentrations in
      another AD model (TgCRND8). Three-month-old 5XFAD and wild-type littermate mice
      were treated by intravenous injections of low doses (10 mg/kg) of Brimapitide
      every 3 weeks, for 3 or 6 months (n = 6-9 per group). Cognitive deficits and
      brain lesions were assessed using Y-maze, fear-conditioning test, and
      histological and biochemical methods. Chronic treatment of Brimapitide for 3
      months resulted in a reduction of Abeta plaque burden in the cortex of 5XFAD
      treated mice. After 6 months of treatment, cognitive deficits were reduced but
      also a significant reduction of cell death markers and the pro-inflammatory IL
      1beta cytokine in treated mice were detected. The Abeta plaque burden was not
      anymore modified by the 6 months of treatment. In addition to modulating
      cognition and amyloid plaque accumulation, depending on the treatment duration,
      Brimapitide seems experimentally to reduce neuronal stress in 5XFAD mice.

PMID- 29660944
TI  - Cardiovascular Response to Mental Stress in Mild Cognitive Impairment and its
      Association with Cerebral Perfusion.
AB  - Mental stress has been linked to various chronic diseases including Alzheimer's
      disease, but the mechanisms underlying cognitive decline with mental stress are
      unknown. Reduced cardiovascular response to stress is associated with
      cardiovascular disease, and the latter is associated with cognitive impairment.
      We measured electrodermal activity, blood pressure, and cardiac hemodynamics in
      cognitively normal and mild cognitive impairment (MCI) adults (n = 76, mean age =
      58 years, 46% MCI) during rest, a math test, and face-name recall tasks to derive
      the following cardiovascular indicators: mean arterial pressure, heart rate,
      stroke volume and cardiac output. These indicators were compared between the two
      groups. Cerebral blood perfusion via arterial spin-labeling MRI was measured in a
      subgroup who underwent an MRI scan (n = 30). Following exposure to mental stress,
      a decrease in stroke volume (p = 0.024) and cardiac output (p = 0.005) was found
      in the MCI group, but an increase in both parameters in the cognitively normal
      group. This difference was largest during face-name recall (standardized
      difference in stroke volume = -0.50, p = 0.029, and in cardiac output = -0.52, p
      = 0.023). Cardiac output during mental stress, but not at rest, decreased with
      cerebral perfusion (normal: p = 0.078, beta= 1.97, R2 = 0.090; MCI: p = 0.007,
      beta= 2.02, R2 = 0.008). No significant difference was found between the two
      groups at rest. This preliminary study suggests that individuals with MCI have an
      insufficient cardiac output, and in turn lower cerebral perfusion in response to
      mental stress.

PMID- 29660943
TI  - Circulating, Cell-Free Micro-RNA Profiles Reflect Discordant Development of
      Dementia in Monozygotic Twins.
AB  - We aim to examine if circulating micro-RNA and cytokine levels associate with
      dementia diagnosis and cognitive scores. To test our hypothesis, we use plasma
      donated from 48 monozygotic twin pairs in 1997 and 46 micro-RNAs and 10 cytokines
      were quantified using microfluidic RT-qPCR and multiplex solid-phase
      immunoassays, respectively. Micro-RNA and cytokine profiling were examined for
      associations with dementia diagnoses in a longitudinal registry study or with
      cognitive scores at baseline. Thirty-six micro-RNAs and all cytokines were
      detected consistently. Micro-RNA profiles associate with diagnoses and cognitive
      scores at statistically significant levels while cytokine only showed trends
      pointing at chronic inflammation in twins having or developing dementia. The most
      notable findings were decreased miR-106a and miR-210, and increased miR-106b
      expression in twins with a dementia diagnosis. This pioneering evaluation of
      micro-RNA and cytokine and dementia diagnosis suggests micro-RNA targets in
      vasculogenesis, lipoprotein transport, and amyloid precursor protein genes.

PMID- 29660945
TI  - TRPC1 Null Exacerbates Memory Deficit and Apoptosis Induced by Amyloid-beta.
AB  - The transient receptor potential cation (TRPC) channels are widely expressed in
      nervous system but their functions remain largely unclear. Here, we found that
      TRPC1 deletion did not affect learning and memory in physiological conditions,
      while it aggravated learning and memory deficits induced by amyloid-beta (Abeta),
      the major component of the senile plaques observed in the brains of Alzheimer's
      disease (AD). Further studies demonstrated that TRPC1 deletion did not affect
      cell apoptosis in physiological condition, but it exacerbated the Abeta-induced
      cell death in mouse hippocampus. Moreover, the level of TRPC1 was decreased in AD
      cell and mouse models, and upregulation of TRPC1 decreased Abeta levels with
      attenuation of apoptosis in the cells stably overexpressing amyloid-beta protein
      precursor (AbetaPP). Finally, the transmembrane domain of TRPC1 could bind to
      AbetaPP and thus decreased Abeta production. These findings indicate that loss of
      TRPC1 exacerbates Abeta-induced memory deficit and cell apoptosis, though it does
      not impair cognitive function or induce cell death in physiological conditions.

PMID- 29660942
TI  - The Role of the Gut Microbiota in the Metabolism of Polyphenols as Characterized
      by Gnotobiotic Mice.
AB  - A growing body of experimental data suggests that microbes in the gut influence
      behavior and can alter brain physiology and neurochemistry. Although promising,
      researchers are only starting to understand the potential of the gut microbiota
      for use in neurological disease. Recent evidence demonstrated that
      gastrointestinal activities are linked to mood disorders such as anxiety,
      depression, and most recently, cognitive functions in age-related
      neurodegenerative disorders. Studies from our group and others are uncovering new
      evidence suggesting that the gut microbiota plays a crucial role in the
      metabolism and bioavailability of certain dietary compounds and synthetic drugs.
      Based on this evidence, this review article will discuss the implications of the
      gut microbiota in mechanisms of bioavailability and biotransformation with an
      emphasis on dietary polyphenol compounds. This will be followed by a survey of
      ongoing innovative research identifying the ability of individual gut bacteria to
      enhance the bioavailability of gut-derived, brain-penetrating, bioactive
      polyphenol metabolites that ultimately influence mechanisms associated with the
      promotion of resilience against psychological and cognitive impairment in
      response to stress. Lastly, current research initiatives aimed at promoting the
      generation of brain bioactive polyphenol metabolites by specialized gut microbes
      will be discussed, specifically the use of gnotobiotic mice to develop
      bioengineered second generation probiotics. We propose that leveraging the gut
      microbial ecosystem to generate brain targeted bioactive metabolites from dietary
      polyphenols can attenuate lifestyle risk factors and promote resilience against
      age-related cognitive decline.

PMID- 29660946
TI  - PET Tau and Amyloid-beta Burden in Mild Alzheimer's Disease: Divergent
      Relationship with Age, Cognition, and Cerebrospinal Fluid Biomarkers.

PMID- 29660947
TI  - Effects of Walkbot gait training on kinematics, kinetics, and clinical gait
      function in paraplegia and quadriplegia.
AB  - BACKGROUND: The robotic-assisted gait training (RAGT) system has gained
      recognition as an innovative, effective paradigm to improve functional ambulation
      and activities of daily living in spinal cord injury and stroke. However, the
      effects of the Walkbot robotic-assisted gait training system with a specialized
      hip-knee-ankle actuator have never been examined in the paraplegia and
      quadriplegia population. OBJECTIVE: The aim of this study was to determine the
      long-term effects of Walkbot training on clinical for hips and knee stiffness in
      individuals with paraplegia or quadriplegia. METHODS: Nine adults with subacute
      or chronic paraplegia resulting from spinal cord injury or quadriplegia resulting
      from cerebral vascular accident (CVA) and/or hypoxia underwent progressive
      conventional gait retraining combined with the Walkbot RAGT for 5 days/week over
      an average of 43 sessions for 8 weeks. Clinical outcomes were measured with the
      Functional Ambulation Category (FAC), Modified Rankin Scale (MRS), Korean version
      of the Modified Barthel Index (K-MBI), Modified Ashworth Scale (MAS). Kinetic and
      kinematic data were collected via a built-in Walkbot program. RESULTS: Wilcoxon
      signed-rank tests showed significant positive intervention effects on K-MBI,
      maximal hip flexion and extension, maximal knee flexion, active torque in the
      knee joint, resistive torque, and stiffness in the hip joint (P <  0.05). These
      findings suggest that the Walkbot RAGT was effective for improving knee and hip
      kinematics and the active knee joint moment while decreasing hip resistive force.
      These improvements were associated with functional recovery in gait, balance,
      mobility and daily activities. CONCLUSIONS: These findings suggest that the
      Walkbot RAGT was effective for improving knee and hip kinematics and the active
      knee joint moment while decreasing hip resistive force. This is the first
      clinical evidence for intensive, long-term effects of the Walkbot RAGT on active
      or resistive moments and stiffness associated with spasticity and functional
      mobility in individuals with subacute or chronic paraplegia or quadriplegia who
      had reached a plateau in motor recovery after conventional therapy.

PMID- 29660948
TI  - The cardiac autonomic nervous system response to different daily demands among
      patients at the sub-acute phase post ischemic stroke and healthy controls.
AB  - BACKGROUND: Autonomic disturbances are a common phenomenon in patients' post
      stroke, characterized by hypo function of the para-sympathetic and/or overactive
      sympathetic system. The impact of autonomic disturbances on physical therapy
      tasks during the rehabilitation period has not yet been assessed. OBJECTIVE: To
      describe the response of the cardiac autonomic nervous system during different
      tasks, among patients and age-matched healthy controls. METHODS: Nineteen
      patients in the subacute phase post first-ever ischemic stroke, and 16 controls.
      The Polar advanced heart rate monitor (RS800CX) was used to record RR intervals
      at rest, during paced breathing exercise, while performing different types of
      muscle contractions, and during single and dual task conditions. RESULTS: RR
      intervals and heart-rate variability (HRV) parameters were significantly lower
      among patients post stroke, both at rest and during most of the activities
      tested. Among the control group a significant autonomic adaptation was seen in
      the form of reduced RR intervals and HRV during muscle contraction and a
      significant increase in these parameters during slow breathing, no significant
      changes were observed among patients post stroke. CONCLUSION: Patients post
      stroke experience hyper sympathetic function at rest and less adaptive cardiac
      autonomic control during different activities, which all may have an impact on
      rehabilitation outcomes.

PMID- 29660950
TI  - Impact of balance on functional independence after stroke: A cross-sectional
      study at rehabilitation settings in Nigeria.
AB  - BACKGROUND: Functional independence is often compromised after stroke and its
      restoration is one of the goals of stroke rehabilitation. OBJECTIVE: This study
      assessed the impact of balance on functional independence after stroke. METHODS:
      Ninety-five stroke patients undergoing physical rehabilitation at two health
      institutions in Nigeria participated in the study. Balance and functional
      independence were respectively assessed with the Berg Balance Scale and the
      Barthel Index. Binary logistic regression analysis was conducted to examine the
      independent impact of balance on functional independence while controlling for
      participants' age, sex, side of hemiparesis and post-stroke duration. RESULTS:
      Mean+/-SD age of the participants was 58.4+/-13.1 years and females were more (f
      = 48; %  = 50.5). The regression model from the binary regression analysis
      explained 73.2% (Nagelkerke R2 = 0.732) of the variance in functional
      independence. Good balance function was found to independently and significantly
      (P <  0.01) increase the likelihood of being functionally independent after
      stroke (Odds ratio = 1.33; 95% CI = 1.11 to 1.58). CONCLUSION: The goal of
      attaining functional independence after stroke may depend to a significant extent
      on good balance function irrespective of the stroke survivor's age, sex and post
      stroke duration.

PMID- 29660951
TI  - Effects of neuromuscular electrical stimulation in patients with Parkinson's
      disease and dysphagia: A randomized, single-blind, placebo-controlled trial.
AB  - BACKGROUND: Neuromuscular electrical stimulation has been used to improve
      swallowing function in neurologic patients with dysphagia, but its effect on
      patients with dysphagia and Parkinson's disease remains unclear. OBJECTIVES: This
      study aimed to identify the effect of effortful swallowing combined with
      neuromuscular electrical stimulation as a novel treatment approach in dysphagic
      patients with Parkinson's disease. METHODS: Participants were randomly allocated
      to an experimental group (n = 9) or a placebo group (n = 9). The experimental
      group simultaneously received neuromuscular electrical stimulation with effortful
      swallowing, while the placebo group received sham neuromuscular electrical
      stimulation with effortful swallowing. All participants received the treatment
      for 30 min/day at five sessions per week for 4 weeks. Both groups also received
      the same conventional dysphagia therapy. RESULTS: The experimental group showed
      significant differences in horizontal movement (p = 0.038) and vertical movement
      (p = 0.042) compared to the placebo group, but showed no significant differences
      in the oral (p = 0.648) or pharyngeal phase (p = 0.329) of the Videofluoroscopic
      Dysphagia Scale compared to the placebo group, except for the Penetration
      Aspiration Scale (p = 0.039). CONCLUSIONS: We demonstrated that neuromuscular
      electrical stimulation applied to the infrahyoid region combined with effortful
      swallowing effectively increased hyoid bone movement and reduced aspiration in
      dysphagic patients with Parkinson's disease.

PMID- 29660952
TI  - Objective motor assessment for personalized rehabilitation of upper extremity in
      brain injury patients.
AB  - BACKGROUND: The increasing number of patients with acquired brain injury and the
      current subjectivity of the conventional upper extremity (UE) assessment tests
      require new objective assessment techniques. OBJECTIVE: This research proposes a
      novel objective motor assessment (OMA) methodology based on the Fugl-Meyer
      assessment (FMA). The goals are to automatically calculate the objective scores
      (OSs) of FMA-UE movements (as well as a global OS) and to interpret the estimated
      OSs. METHODS: Fifteen patients participated in the study. The OMA algorithm was
      designed to detect small-scale variations in UE movements. The OSs for 14 FMA-UE
      movements and the global OSs were automatically calculated using the algorithm
      and evaluated by 2 therapists. The interpretation of the global OSs was performed
      at 3 levels: by item, movement and globally. RESULTS: The global OSs calculated
      by our algorithm had a significant correlation with the therapists' scores (0.783
      and 0.938, p <  0.01). All OSs for each movement were correlated with the scores
      given by the therapists. The correlation coefficient can reach values as high as
      0.981 (p <  0.01). CONCLUSIONS: We provide a new objective assessment tool for
      therapists to help them improve the diagnostic accuracy and to achieve a more
      personalized and potentially effective physical rehabilitation of brain injury
      patients.

PMID- 29660953
TI  - Whole-body vibration improves ankle spasticity, balance, and walking ability in
      individuals with incomplete cervical spinal cord injury.
AB  - OBJECTIVES: This study aimed to investigate the effects of whole-body vibration
      (WBV) training on ankle spasticity, balance, and walking ability in patients with
      incomplete spinal cord injury (iSCI) at cervical level. METHODS: Twenty-eight
      patients with cervical iSCI were randomly assigned to WBV (n = 14) or control
      group (n = 14). WBV group received WBV training, while control group was treated
      with placebo-treatment. All interventions were given for 20-min, twice a day, 5
      days a week for 8-weeks. The spasticity of ankle plantar-flexors was assessed by
      estimating passive resistive force using a hand-held dynamometer. Balance was
      analyzed based on postural sway length (PSL) using a force plate. Timed-Up and Go
      test (TUG) and 10 m-Walk Test (10MWT) were used to assess walking ability.
      RESULTS: Both groups showed significant improvements in spasticity, balance and
      walking ability. Also, the significant differences between two groups were
      demonstrated in the outcomes of spasticity (3.0+/-1.7 vs 0.9+/-1.2), PSL (6.4+/
      1.2 vs 3.2+/-0.9 with eyes-open, and 15.1+/-10.9 vs 7.4+/-4.3 with eyes-closed),
      TUG (2.3+/-1.3 vs 1.0+/-1.0), and 10MWT (3.5+/-2.3 vs 1.3+/-1.4). CONCLUSIONS:
      WBV may be a safe and effective intervention to improve spasticity, balance and
      walking ability in individuals with cervical iSCI. Thus, WBV may be used to
      improve these symptoms in clinics.

PMID- 29660949
TI  - Concussion and the autonomic nervous system: An introduction to the field and the
      results of a systematic review.
AB  - BACKGROUND: Recent evidence suggests that autonomic nervous dysfunction may be
      one of many potential factors contributing to persisting post-concussion
      symptoms. OBJECTIVE: This is the first systematic review to explore the impact of
      concussion on multiple aspects of autonomic nervous system functioning. METHODS:
      The methods employed are in compliance with the American Academy of Neurology
      (AAN) and PRISMA standards. Embase, MEDLINE, PsychINFO, and Science Citation
      Index literature searches were performed using relevant indexing terms for
      articles published prior to the end of December 2016. Data extraction was
      performed by two independent groups, including study quality indicators to
      determine potential risk for bias according to the 4-tiered classification scheme
      of the AAN. RESULTS: Thirty-six articles qualified for inclusion in the analysis.
      Only three studies (one Class II and two Class IV) did not identify anomalies in
      measures of ANS functioning in concussed populations. CONCLUSIONS: The evidence
      supports the conclusion that it is likely that concussion causes autonomic
      nervous system anomalies. An awareness of this relationship increases our
      understanding of the physical impact of concussion, partially explains the
      overlap of concussion symptoms with other medical conditions, presents
      opportunities for further research, and has the potential to powerfully inform
      treatment decisions.

PMID- 29660954
TI  - Usability of the Thera-Band(r) to improve foot drop in stroke survivors.
AB  - BACKGROUND: Stroke survivors show "foot drop", dragging their toes on the ground
      in the swing phase of gait. Ineffective ankle dorsiflexion may result in an
      abnormal gait pattern. OBJECTIVE: The purpose of this study was to investigate
      the effect of ankle Thera-Band(r) use on gait patterns in stroke survivors.
      METHODS: Gait data were collected in eight subjects who had had strokes using
      gait analysis system, both with and without the Thera-Band(r). The following
      dependent variables of gait parameters were analyzed: velocity, cadence, step
      length, stride length, single support time, and double support time. RESULTS:
      There were significant improvements in gait velocity, cadence, stride length, and
      double support time in those who used the Thera-Band(r) compared to those who did
      not (p <  0.05). However, there were no significant differences in step length or
      single support time (p >  0.05). CONCLUSIONS: The results show that ankle Thera
      Band(r) use may have a positive effect in improving gait parameters by increasing
      the ankle stability in stroke survivors with foot drop. Its usefulness in the
      rehabilitation of foot drop in stroke survivors needs to be further investigated.

PMID- 29660955
TI  - Change in mobility function and its causes in adults with cerebral palsy by Gross
      Motor Function Classification System level: A cross-sectional questionnaire
      study.
AB  - BACKGROUND: The prognosis for mobility function by Gross Motor Function
      Classification System (GMFCS) level is vital as a guide to rehabilitation for
      people with cerebral palsy. OBJECTIVE: This study sought to investigate change in
      mobility function and its causes in adults with cerebral palsy by GMFCS level.
      METHODS: We conducted a cross-sectional questionnaire study. RESULTS: A total of
      386 participants (26 y 8 m, SD 5 y 10 m) with cerebral palsy were analyzed.
      Participant numbers by GMFCS level were: I (53), II (139), III (74) and IV (120).
      The median age of participants with peak mobility function in GMFCS level III was
      younger than that in the other levels. 48% had experienced a decline in mobility.
      A Kaplan-Meier plot showed the risk of mobility decline increased in GMFCS level
      III; the hazard ratio was 1.97 (95% CI, 1.20-3.23) compared with level I. The
      frequently reported causes of mobility decline were changes in environment, and
      illness and injury in GMFCS level III, stiffness and deformity in level IV, and
      reduced physical activity in level II and III. CONCLUSIONS: Peak mobility
      function and mobility decline occurred at a younger age in GMFCS level III, with
      the cause of mobility decline differing by GMFCS level.

PMID- 29660956
TI  - Effect of virtual reality training on walking distance and physical fitness in
      individuals with Parkinson's disease.
AB  - OBJECTIVE: To evaluate the effects of gait training with virtual reality (VR) on
      walking distance and physical fitness in individuals with Parkinson's Disease
      (PD). METHODS: Thirty-seven individuals with PD participated in this prospective,
      randomized, controlled clinical trial. They were randomly allocated to a control
      group submitted to conventional training (n = 12), a treadmill group submitted to
      gait training on a treadmill (n = 13) and a VR group submitted to gait training
      using the XboxTM (n = 12). Clinical measures, gait variables and the Six-Minute
      Walk Test (6MWT) were evaluated: pre-intervention, after one intervention
      session, post-intervention and follow up (30 days after intervention). RESULTS:
      The VR and treadmill groups travelled longer distances on the 6MWT and had faster
      gait speed in comparison to the control group. The VR and treadmill groups
      demonstrated an increase in pre-6MWT HR. The VR group had more intense HR after
      the first session and throughout training, but these gains were not maintained at
      the follow-up. CONCLUSION: The present findings demonstrate that gait training
      with a VR program is as effective as treadmill training with regard to gains in
      walking distance and improvements in temporal gait variables in individuals with
      PD.

PMID- 29660957
TI  - A systematic review and meta-analysis of educational interventions for children
      and adolescents with acquired brain injury.
AB  - BACKGROUND: Children with brain injuries face significant challenges in their
      recovery. One of the greatest is transitioning from hospital/home to school where
      they face issues such as reintegration, lack of understanding and catching up
      with missed work. Many children struggle with their altered circumstances and
      require additional supports to meet the academic demands of systems which are ill
      equipped to teach them. OBJECTIVE: To summarise the best available evidence for
      the use of educational interventions to improve academic attainment in childhood
      survivors of acquired brain injury (ABI). METHODS: Six electronic databases
      (Cinahl, Embase, Medline, PsycINFO, Pubmed, & Web of Science) were systematically
      searched for randomised controlled trials published between 1980 and 2017. Two
      authors independently reviewed these studies and extracted data on type of
      intervention, characteristics of participants, outcome measures, findings and
      recommendations. The Cochrane Collaboration's Risk of Bias tool was used to
      assess systematic error in the included studies. RESULTS: Four studies met the
      inclusion criteria (n = 296 children and adolescents). Three studies (n = 287)
      were included in meta-analysis for the primary outcome which showed no
      statistically significant difference between the intervention and control
      conditions on academic attainment (SMD 1.31, 95% CI -0.06 to 2.68, p = 0.06). No
      statistically significant differences were found which favoured the intervention
      for the secondary outcomes of attention, internalising or externalising behavior.
      All effect sizes were considered as small. CONCLUSIONS: This review suggests that
      no currently effective educational interventions exist for children with ABI.
      Greater efforts are required to produce effective and rigorously tested
      interventions to improve outcomes for these children.

PMID- 29660958
TI  - Immersive virtual reality in traumatic brain injury rehabilitation: A literature
      review.
AB  - BACKGROUND: Traumatic brain injury (TBI) is a common cause of morbidity and
      mortality in the United States with its sequelae often affecting individuals long
      after the initial injury. Innovations in virtual reality (VR) technology may
      offer potential therapy options in the recovery from such injuries. However,
      there is currently no consensus regarding the efficacy of VR in the setting of
      TBI rehabilitation. OBJECTIVE: The aim of this review is to evaluate and
      summarize the current literature regarding immersive VR in the rehabilitation of
      those with TBI. METHODS: A comprehensive literature search was conducted
      utilizing PubMed, Google Scholar, and the Cochrane Review using the search terms
      "virtual reality," "traumatic brain injury," "brain injury," and "immersive."
      RESULTS: A total of 11 studies were evaluated. These were primarily of low-level
      evidence, with the exception of two randomized, controlled trials. 10 of 11
      studies demonstrated improvement with VR therapy. VR was most frequently used to
      address gait or cognitive deficits. CONCLUSIONS: While the current literature
      generally offers support for the use of VR in TBI recovery, there is a paucity of
      strong evidence to support its widespread use. The increasing availability of
      immersive VR technology offers the potential for engaging therapy in TBI
      rehabilitation, but its utility remains uncertain given the limited studies
      available at this time.

PMID- 29660959
TI  - Application of clean intermittent catheterization for neurogenic bladder in
      infants less than 1 year old.
AB  - BACKGROUND: Neurogenic bladder (NB) is a common pediatric urological disease
      caused by a variety of neurological pathologies. Clean intermittent
      catheterization (CIC) has been the preferred method to empty bladder. OBJECTIVE:
      To investigate the effect of CIC on preserving bladder and upper urinary tract
      function in infants less than 1 year old with NB. METHODS: A retrospective
      analysis was conducted on 76 infants with NB. Patients were divided into two
      groups according to treatment initiation: the early CIC group (ECG) (<1 year old)
      and the late CIC group (LCG) (>3 years old). RESULTS: Bladder compliance (BC),
      safe bladder capacity (SBC) and maximum cystometric capacity (MCC) were
      significantly higher in the ECG than those in the LCG at 6 years of follow-up
      respectively (P <  0.05). The frequencies of vesicoureteral reflux (VUR) and
      urinary tract infection (UTI) in the ECG were significantly lower than those in
      the LCG (P <  0.05) at 6 years of follow-up. Two and nine patients exhibited mild
      renal damage in the ECG and LCG, respectively, resulting in a significant
      difference (P <  0.05) at 6 years of follow-up. CONCLUSION: Early CIC plays an
      important role in preserving bladder function and preventing UTI and renal
      deterioration in infants with NB, especially in the first year of life.

PMID- 29660960
TI  - Are functional mobility tests responsive to group physical therapy intervention
      in individuals with Parkinson's disease?
AB  - BACKGROUND: The Timed up and go test (TUG), the Five times sit-to-stand test
      (FTSTS) and the Bed Mobility test (BMT) are widely used in clinical practice for
      Parkinson Disease (PD). However, no reported studies have evaluated the
      responsiveness to group physical therapy intervention (GPTI). OBJECTIVE: To
      verify if TUG, FTSTS and BMT were responsive to GPTI. METHODS: Thirty individuals
      with PD were assessed prior to and after an 8-week evidence-based GPTI. Paired t
      test was used to determine statistically significant change pre-and post
      intervention. Internal responsiveness (IR) was classified with the standardized
      response mean (SRM). A 5-point Likert scale assessed self-perceived performance
      by the subjects after the intervention. Analysis of the receiver operating
      characteristic (ROC) curve was used to determine the accuracy and cut-off scores
      for identifying participants who had shown improvement. RESULTS: GPTI was
      efficient in improving real (p<=0.001) and self-perceived mobility performance in
      all measures. All tests were responsive to changes: the IR varied from medium to
      high (SRM = 0.7-1.5); the cut-off point for TUG test was >2.2 s, for FTSTS test
      was >2.5 s and for BM test >1.4 s. CONCLUSIONS: The TUG, FTSTS and BMT were
      responsive to the GPTI and accurately detected meaningful clinical changes. Our
      results provide an important information about the clinical application of these
      tests in PD individuals.

PMID- 29660961
TI  - An international perspective on educators' perceptions of children with Traumatic
      Brain Injury.
AB  - BACKGROUND: Educators lack understanding of traumatic brain injury (TBI), which
      can lead to a lack of appropriate assessment and intervention methods for these
      students. OBJECTIVE(S): This qualitative study explored what experienced teachers
      perceive, believe, and know about pediatric TBI. METHODS: Following development
      of a standardized interview protocol, 46 teachers from Australia, New Zealand,
      Northern Ireland, and the United States took part in semi-structured interviews.
      Topics included understanding of the effects of TBI on school performance,
      supporting a child with TBI in the classroom, and challenges and teaching
      efficacy in working with students with TBI. RESULTS: The themes we identified
      were: personal experience with TBI, lack of content knowledge, non-TBI-specific
      adaptations, collaboration with experts, need for specific training, confidence
      in working with students with TBI, and knowledge of students' rights to service
      provision. Our findings show that although teachers had little knowledge of TBI,
      many felt they would be able to adequately support a child with appropriate input
      from specialists. CONCLUSION: Teachers fill their knowledge gaps about TBI with
      their own personal experiences and prior information about working with students
      with disabilities. These findings support important implications for changes in
      how we educate and support teachers.

PMID- 29660962
TI  - Return to learn: Transitioning to school and through ascending levels of academic
      support for students following a concussion.
AB  - PURPOSE: The purpose of this article is to familiarize healthcare providers and
      parents with educational language, laws, and processes as they relate to a
      comprehensive ascending level of academic supports as it pertains to promoting a
      smooth and supported transition to school following a concussion. BACKGROUND:
      Returning to learn (RTL) following a concussion is of parallel importance to
      returning to sport (RTS). A successful RTL is a critical part of concussion
      management. Many RTL articles advise healthcare providers and parents to request
      formalized educational supports, also known as Tier 2 or Tier 3 services, for
      children with concussion as they return to school. FINDINGS: Premature requests
      for formal (Tier 2 or 3) educational services, rather than allowing for immediate
      informal educational supports (known as Tier 1), can actually delay academic
      supports and have the potential to cause adversarial relationships between
      parents and schools. Additionally, this practice contradicts current research
      demonstrating the need for fast, flexible, temporary academic supports within the
      first month post-injury. CONCLUSION: Allowing school districts to direct the
      application of existing ascending levels of educational support for students with
      concussion as they return to school can promote robust and positive outcomes.

PMID- 29660963
TI  - Readiness to recognize: A qualitative case study of educational identification of
      TBI.
AB  - BACKGROUND: The educational identification (ED-ID) of students with traumatic
      brain injury (TBI) has been legislated in numerous states, and TBI has become its
      own special education category. Questions abound as to whether these changes will
      lead to more readily identifying these students to provide appropriate special
      education supports. OBJECTIVE: Elucidate one state's response to legislative
      changes around ED-ID of TBI. METHODS: This is a phenomenological case study of
      nine school districts in one state. Researchers conducted focus groups as well as
      individual interviews with various special education staff. On-going analysis of
      the focus group and interview data occurred, until themes were finalized.
      RESULTS: Reactions of staff comprised two opposing viewpoints: those supporting
      and carrying out ED-ID ("Toward ED-ID") and those describing processes and
      attitudes that stand in the way ("Barriers"). Themes that were supportive of ED
      ID include Credible History, Personnel, Targeted Intervention, Effective
      Communication, and Education. Themes aligned with the barrier viewpoint include
      Concussion Protocols, Medical Nature, Misidentification, Stigma, and
      Communication Breakdown. CONCLUSION: While many districts reported success with
      ED-ID for TBI, responses to the ED-ID legislation and TBI category were mixed,
      with enough barriers identified to cause concern over whether the legislative and
      policy changes have been overall beneficial.

PMID- 29660964
TI  - Hospital to school transition following traumatic brain injury: A qualitative
      longitudinal study.
AB  - BACKGROUND: The transition from hospital to school is regarded by researchers as
      a key factor in the educational success of students with traumatic brain injury
      (TBI). OBJECTIVES: The objective of this study is to look closely at what
      transition services consist of, how they are delivered, and how they are received
      by educators. METHODS: Parents and educators of 21 students with TBI participated
      in a qualitative study of the delivery of transition services and implementation
      of hospital recommendations. RESULTS: This paper presents two themes that emerged
      from interview and observational data collected over a 7-year period: 1)
      provision of hospital-school transition services is inconsistent and 2) teachers
      lack sufficient awareness of and training in TBI to implement hospital transition
      recommendations. Regardless of the type and quality of transition support, most
      educators in the students' schools remained unaware of the students' needs and
      how to meet them. CONCLUSION: Recommendations include more consistent and
      specific communication between hospital and school for all students with TBI,
      long-term tracking of the injury in student files, and increased training of
      educators in how to meet the needs of students with TBI.

PMID- 29660965
TI  - A clinically focused systematic review of social communication in pediatric TBI.
AB  - BACKGROUND: Social communication is a persistent area of need after pediatric
      traumatic brain injury; however, it continues to be misunderstood, under
      recognized, and under-treated. Clinicians must have a working understanding of
      current evidence and practice recommendations to support practice. OBJECTIVES: 1)
      To analyze recent evidence in social communication published in the last ten
      years, which is specific to pediatric TBI and 2) To translate these findings for
      clinicians. METHODS: A systematic literature review was conducted. Ninety-five
      articles met criteria for full analysis. For analysis, articles were grouped
      according five themes: 1) Theoretical/Review; 2) Etiology/Characteristics; 3)
      Recovery/Outcome; 4) Assessment; or 5) Intervention. Article findings were then
      extracted, translated, and summarized. RESULTS: The majority of articles focused
      on describing characteristics of social communication deficits after pediatric
      TBI, documenting recovery, and identifying factors that contribute to outcome.
      Research on the relationship of development, age at injury, injury severity, and
      environmental factors with social communication outcomes requires additional
      attention. Research in assessment and treatment is critically sparse. CONCLUSION:
      The results of this review highlight both the progress that has been made in
      understanding the phenomena of social communication deficits in pediatric TBI and
      the critical need for basic and translational research in assessment and
      intervention.

PMID- 29660966
TI  - Community-based interventions for adolescents following traumatic brain injury: A
      systematic review.
AB  - BACKGROUND: Chronic impairment following childhood traumatic brain injury has the
      potential to increase risk of negative outcomes. This highlights potential value
      in community-based rehabilitation programs. OBJECTIVES: To identify research
      studies examining existing intervention programmes available in community-based
      rehabilitation to adolescents following TBI to assist with the transition back
      into the community. METHODS: A systematic review of community-based interventions
      was conducted across different national contexts. All included studies involved a
      clinical population with TBI, aged 11 to 25 years inclusive. Risk of bias was
      rated for each included study. RESULTS: Seventeen studies were identified for
      inclusion in the review, of these eleven distinct interventions were found. The
      quality of evidence was largely weak and highly variable. CONCLUSION: The results
      suggest some improvement in adolescent outcomes following community-based
      interventions, however higher quality evidence is needed to support specific
      interventions.

PMID- 29660967
TI  - A call for implementing preferred practices for brain injury screening in youth
      to improve transition.
AB  - BACKGROUND: It is vital to engage in systematic screening to identify and serve
      children who may have sustained an acquired brain injury (ABI) - either traumatic
      or non-traumatic, so they can be successfully transitioned between environments
      and life stages. This is particularly important for children and adolescents
      given the impact an ABI can have on learning and social functioning over the
      course of the neurodevelopmental process. A pattern of repeated, undiagnosed mild
      brain injuries may lead to mood or behavior disorders, learning problems. Despite
      increasing awareness of brain injury as a public health issue, there has not been
      implementation of systematic screening practices in schools or other public
      health settings similar to other conditions (e.g., vision disorders, Autism
      Spectrum Disorders). OBJECTIVES: What is needed to address this lack of
      systematic screening for ABI is a rationale for systematic screening for ABI in
      children and adolescents, including examining successful models of screening for
      other disorders and conditions. METHODS: A review was conducted of available ABI
      screening methods, including a description of the available screening tools for
      pediatric ABI, along with supporting research findings. RESULTS: A comparison was
      made of these pediatric ABI screening tools, looking at the purpose of the tool,
      the populations and settings in which the tool can be used, the time and cost for
      administering the tool, the evidence basis in the literature supporting the tool,
      and the types of outcomes that can be attained from using the tool. CONCLUSION:
      Recommendations are made for procedures for systematically implementing ABI
      screening in pediatric settings including schools, primary care providers, mental
      health, and juvenile justice systems to improve the access to brain injury
      services and affording more successful transition of adolescents into the adult
      roles.

PMID- 29660968
TI  - Rehabilitation and school services following traumatic brain injury in young
      children.
AB  - BACKGROUND: Preschool children have the highest incidence of emergency department
      visits for traumatic brain injury (TBI) with the majority discharged home without
      a single point of entry into follow-up services. This paper describes families'
      experience with service access following TBI. OBJECTIVES: To describe parent
      reported service utilization following preschool TBI and examine predictors of
      service access. METHODS: Participants (N = 80) were drawn from the first visit of
      a longitudinal study examining elementary school outcomes following TBI. Parents
      were interviewed about their service history. Descriptive statistics analyzed
      sample demographics. Logistic regression examined associations between injury
      related factors and service utilization. RESULTS: TBI participants had mild
      injuries (83%) and were either discharged to home or spent less than a week in
      the hospital. No TBI participants received inpatient rehabilitation and only a
      portion of the sample (26%) received outpatient treatment. Length of hospital
      stay was a significant predictor of service access (Wald = 4.33, df = 1, p =
      0.040). All children were enrolled in preschool without accommodations.
      CONCLUSION: Currently no systematic continuum of care exists for children with
      TBI injured prior to elementary school, despite availability of healthcare,
      education and state based resources. Healthcare professionals in contact with
      young children can help with follow-up by educating parents about TBI effects on
      learning.

PMID- 29660969
TI  - Self-regulation strategies used by students with brain injury while transitioning
      to college.
AB  - PURPOSE: Students with TBI enter college with strategies that they have used
      prior to being injured yet often without knowing which ones will be effective in
      helping them to be successful. The purpose here is to describe how semi
      structured interviews were used to identify self-regulated learning strategies,
      to demonstrate the utility and reliability of coding self-regulated learning
      strategies, and to provide examples of student-centered goals derived from survey
      and interview responses. METHODS: College students completed the College Survey
      for Students with Brain Injury (CSS-BI) and were interviewed before and after
      coaching support that focused on teaching self-regulated learning. Responses to
      interview questions about strategies were coded using a modified version of
      Zimmerman and Martinez-Pons's (1986) schema. Coders also rated strategies for
      specificity. RESULTS: Strategies were reliably coded into 16 categories of self
      regulation. Inter and intra-reliability were strong. Four of the five students
      reported using a larger variety of self-regulation strategies and strategies that
      were more specific after coaching support. DISCUSSION AND CONCLUSIONS: It is
      possible to reliably code self-regulation learning strategies reported by college
      students with TBI. These measures have potential as functional 'outcomes' for
      students who are transitioning to college. Interview responses can be used to
      collaboratively create student-centered goals.

PMID- 29660970
TI  - Inflammation and rehabilitation outcomes in patients with nontraumatic
      intracranial haemorrhage.
AB  - BACKGROUND: Systemic inflammation and its impact on rehabilitation for patients
      with non-traumatic haemorrhagic injury (HBI) sequelae has not yet been adequately
      documented. OBJECTIVE AND METHODS: We therefore considered 31 patients with HBI,
      to determine the serum levels of inflammatory markers (C-Reactive Protein, CRP
      and or interleukine-6, IL-6) to establish their impact on functional status
      (Functional Independence Measure, FIM: 18 indicating the worst performance and
      126, a normal score). RESULTS: The results showed an inflammation prevalence (CRP
      >0.5 mg/dl and/or IL 6 >7 pg/ml) of 74.2% at admission to Rehab. FIM reduction
      was more pronounced in inflamed compared to non-inflamed subjects (p <  0.05) and
      significantly correlated with blood variables sensitive to inflammation, such as
      alpha 1 globulin (r = - 0.565) and neutrophil/ lymphocyte ratio (r = - 0.52), CRP
      (r = - 0.365). At discharge from Rehab, the inflammation rate diminished.
      Inflamed patients showed similar gains in FIM score as their controls. In the
      entire population, the FIM gain was significantly associated with a gain in serum
      albumin, only (r = +0.56). CONCLUSIONS: We conclude that systemic inflammation is
      prevalent in HBI patients and contributes to reduce patient functional status.
      However, during the Rehab stage, inflammation does not hinder the improvement
      rate of functional capacity.

PMID- 29660973
TI  - Computation of hemodynamics in eccentric coronary stenosis: A morphological
      parametric study.
AB  - BACKGROUND: Flow recirculation occurs in eccentric coronary stenosis, which can
      lead to adverse outcome. The complex local geodesic patterns of eccentric
      stenosis are critical factors in determining the flow characteristics in post
      stenotic flow. OBJECTIVE: The main objective of this study is to relate the
      relationship between the detailed morphological parameters in eccentric coronary
      stenosis and the post-stenotic flow characteristics. METHODS: Several idealized
      eccentric coronary stenosis models with variable morphological parameters are
      created to conduct a series of computational fluid dynamics analysis. The impact
      of four specific lesion morphological parameters, eccentricity index (EI),
      diameter stenosis (DS), stenosis length (SL) and shape of lesion, are
      investigated. RESULTS: When EI is small (< 0.33), the length of recirculation
      zones would increase as EI increase; while when EI is large (> 0.33), it would
      decreased as EI increase; Larger magnitude of retrograde flow occurs in models
      with smaller EIs. Both the recirculation zone length and maximum shear rate
      increase significantly as DS increases. Increase of SL will lead to increase of
      recirculation zone length. Higher maximum shear rate and larger recirculation
      zone are observed in models with sharper stenosis shape. CONCLUSIONS: Except DS,
      the detailed geometry patterns (EI, SL and shape of the stenosis) also have great
      impact on post-stenotic flow behaviors in eccentric coronary stenosis.

PMID- 29660974
TI  - In Vivo Spinal Distribution of Cy5.5 Fluorescent Dye after Injection via the
      Lateral Ventricle and Cisterna Magna in Rat Model.
AB  - Objective: The purpose of this study was to find an optimal delivery route for
      clinical trials of intrathecal cell therapy for spinal cord injury in preclinical
      stage. Methods: We compared in vivo distribution of Cy5.5 fluorescent dye in the
      spinal cord region at various time points utilizing in vivo optical imaging
      techniques, which was injected into the lateral ventricle (LV) or cisterna magna
      (CM) of rats. Results: Although CM locates nearer to the spinal cord than the LV,
      significantly higher signal of Cy5.5 was detected in the thoracic and lumbar
      spinal cord region at all time points tested when Cy5.5 was injected into the LV.
      In the LV injection Cy5.5 signal in the thoracic and lumbar spinal cord was
      observed within 12 hours after injection, which was maintained until 72 hours
      after injection. In contrast, Cy5.5 signal was concentrated at the injection site
      in the CM injection at all time points. Conclusion: These data suggested that the
      LV might be suitable for preclinical injection route of therapeutics targeting
      the spinal cord to test their treatment efficacy and biosafety for spinal cord
      diseases in small animal models.

PMID- 29660975
TI  - Synergistic Effects of Psychosocial Stress and Mild Peripheral Infection on
      Inducing Microglial Activation in the Hippocampal Dentate Gyrus and Long-Lasting
      Deficits in Hippocampus-Related Memory.
AB  - Lipopolysaccharide (LPS) treatment and stress may cause immune activation in the
      brain,an event which has been thought to play a role in mediating stress-induced
      cognitive dysfunction.However, the enduring impact of psychosocial stress on
      brain immune activation or cognitive deficitshas not been well investigated.
      Likewise, it remains unexplored whether there exist synergisticeffects of
      psychosocial stress and a weak systemic LPS treatment on brain immune activation
      and/orcognitive function. In this work, a 10-day social defeat regimen was used
      to model psychosocial stressand the number and density of ionized calcium-binding
      adaptor molecule 1 (Iba1)-stained microgliawas used to reveal brain immune
      activation in male Balb/C mice. The social defeat regimen did notcause observable
      microglial activation in dentate gyrus (DG) 24 h after the conclusion of the
      regimen.Microglial activation peaked in DG 24 h following a single 1 mg/kg intra
      peritoneal LPS injection. Atthis time point, DG microglial activation was not
      evident providing 0.125 mg/kg or lower of LPS wasused, this dose of LPS was,
      thus, regarded as the "sub-threshold" in this study. Twenty-four h afterthe
      conclusion of the defeat regimen, mice received a social interaction test to
      determine their defeatstress susceptibility and a "sub-threshold" LPS injection.
      DG microglial activation was observed inthe defeat-stress susceptible, but not in
      the resilient, mice. Furthermore, the stress-susceptible miceshowed impairment in
      object location and Y maze tasks 24 and 72 h after the "sub-threshold"
      LPSinjection. These results suggest that psychosocial stress, when combined with
      a negligible peripheralinfection, may induce long-lasting hippocampus-related
      memory deficits exclusively in subjectssusceptible to psychosocial stresses.

PMID- 29660976
TI  - Oral health-related quality of life and clinical outcomes of immediately or
      delayed loaded implants in the rehabilitation of edentulous jaws: a retrospective
      comparative study.
AB  - BACKGROUND: Patient-centered outcomes are being given great attention by the
      dental scientific community. The Oral Health Impact Profile -14 questionnaire
      (OHIP-14) has been introduced to address patients' success criteria when
      describing the impact of oral rehabilitations on quality of life (OHrQoL).
      METHODS: Thirty-five patients wearing a full-arch implant-prosthesis being in
      place between 4 and 6 years before this analysis were considered eligible and
      then enrolled in the present retrospective study. According to their prosthetic
      anamnesis, two groups were defined: delayed loading group (IL-group) and
      immediate loading group (IL-group). At the moment of analysis, clinical and
      radiographic parameters were collected, and patients were asked to complete the
      Oral Health Impact Profile -14 questionnaire (OHIP-14) in order to measure their
      OHrQoL. RESULTS: Independent t-test showed total OHIP-14 scores to be not
      significantly different between groups; however, the domains "functional
      limitation" and "physical disability" resulted significantly higher in patients
      within the DL-group. On the contrary, social disability was higher in the IL
      group. When the comparison was performed taking sex into account, no significant
      differences between groups were highlighted. Instead, the stratification for
      years of follow-up led to significant evidences. When the follow-up was shorter
      (less-than-5 years), the functional limitation reported scores were higher.
      CONCLUSIONS: Within the limitations of this study, the analysis supports the
      absence of significant differences between immediate loading and delayed loading
      full-arch protocol in term of clinical, radiological parameters and OHrQoL.

PMID- 29660977
TI  - Remediation of Petroleum-Contaminated Soil and Simultaneous Recovery of Oil by
      Fast Pyrolysis.
AB  - Petroleum-contaminated soil (PCS) caused by the accidental release of crude oil
      into the environment, which occurs frequently during oil exploitation worldwide,
      needs efficient and cost-effective remediation. In this study, a fast pyrolysis
      technology was implemented to remediate the PCS and concurrently recover the oil.
      The remediation effect related to pyrolytic parameters, the recovery rate of oil
      and its possible formation pathway, and the physicochemical properties of the
      remediated PCS and its suitability for planting were systematically investigated.
      The results show that 50.9% carbon was recovered in oil, whose quality even
      exceeds that of crude oil. Both extractable total petroleum hydrocarbon (TPH) and
      water-soluble organic matter (SOM) in PCS were completely removed at 500  degrees
      C within 30 min. The remaining carbon in remediated PCS was determined to be in a
      stable and innocuous state, which has no adverse effect on wheat growth. On the
      basis of the systematically characterizations of initial PCS and pyrolytic
      products, a possible thermochemical mechanism was proposed which involves
      evaporation, cracking and polymerization. In addition, the energy consumption
      analysis and remediation effect of various PCSs indicate that fast pyrolysis is a
      viable and cost-effective method for PCS remediation.

PMID- 29660978
TI  - Closed-Loop Electrochemical Recycling of Spent Copper(II) from Etchant Wastewater
      Using a Carbon Nanotube Modified Graphite Felt Anode.
AB  - Developing effective technologies for treatment of spent etchant in printed
      circuit boards industries is of paramount for sustainable copper reuse and
      reducing copper discharge. We developed a novel closed-loop electrochemical cell
      for on-site regeneration of spent acidic cupric chloride etchant. It does not
      have any emissions and recycles all the copper using a three-dimensional graphite
      felt anode decorated with carbon nanotube (CNT/GF). The CNT/GF anode oxidizes
      Cu(I) to Cu(II) so that the spent cuprous chloride can be converted to cupric
      chloride and reused. The decorated CNT layer with abundant oxygen-containing
      functional groups significantly enhanced the electrocatalytic activity for
      Cu(II)/Cu(I) redox. The CuCl32- is oxidized to CuCl+ at the anode and the CuCl+
      is reduced to Cu(0) at the cathode. The closed-loop cycle system converts the
      catholyte into the anolyte. On average, the energy consumption of Cu(I) oxidation
      by CNT/GF is decreased by 12%, comparing to that by untreated graphite felt. The
      oxidation rate of Cu(I) is determined by the current density, and there is no
      delay for the mass transport of Cu(I). This study highlights the outstanding
      electrocatalytic performance, the rapid mass-transfer kinetics, and the excellent
      stability of the CNT/GF electrode, and provides an energy-efficient and zero
      emission strategy for the regeneration of etchant waste.

PMID- 29660979
TI  - Perfluoroalkyl Acids in European Starling Eggs Indicate Landfill and Urban
      Influences in Canadian Terrestrial Environments.
AB  - Perfluoroalkyl acids (PFAAs) were determined in European starling ( Sturnus
      vulgaris) eggs collected between 2009 and 2014 from industrial,
      rural/agricultural, and landfill locations within five urban centers across
      Canada. Within each urban center, perfluoroalkyl sulfonic acid (PFSA)
      concentrations were generally greater in starling eggs collected from
      urban/industrial locations and PFSAs and perfluoroalkyl carboxylic acids (PFCAs)
      were generally greater at landfills compared to rural and remote locations.
      However, the relative importance of urban/industrial versus landfill locations as
      potential sources was chemical- and location-specific. PFSA concentrations in
      eggs collected from nonlandfills were positively correlated with human
      population. Despite the 2000 to 2002 phase-out of perfluorooctanesulfonic acid
      (PFOS) and its C8 precursors, leaching from consumer products during use likely
      continues to be a major source to the environment. In comparison, the
      concentrations of most PFCAs in eggs were not related to population, which
      supports the hypothesis that atmospheric transport and degradation of precursor
      chemicals are influencing their spatial trends. PFAA concentrations in eggs from
      landfills were not correlated with the quantity of waste received by a given
      landfill. The variability in PFAAs between landfills may be due to the specific
      composition of waste items.

PMID- 29660980
TI  - Azabuckybowl-Based Molecular Tweezers as C60 and C70 Receptors.
AB  - We designed and synthesized molecular tweezers consisting of nitrogen-embedded
      buckybowl subunits. The judicious choice of the covalent linkers modulated their
      binding strength with C60 or C70 in solution. Titration studies by optical and 1H
      NMR analyses revealed a 1:1 composition of the resulting complexes. X-ray
      diffraction analysis elucidated their solid-state structures, in which two
      azabuckybowl units surround one fullerene molecule. The large association
      constants stabilize the complexes toward redox reactions and the purification
      process on silica-gel column chromatography. The linker enabled tuning of the
      cavity size for binding of fullerenes, achieving complementary fullerene hosts
      for C60 and C70: the carbazole-bridged dimer preferentially associates with C70
      over C60, while the phenanthrene-bridged dimer interacts with C60 more strongly
      than C70. Electrochemical analysis in combination with density functional theory
      calculations indicated the existence of intermolecular charge-transfer
      interactions between the buckybowl units and the fullerenes. Nonlinear optical
      measurements showed that the two-photon absorption cross sections of the
      molecular tweezers are enhanced upon association with fullerenes.

PMID- 29660981
TI  - Development of Macrocyclic Peptidomimetics Containing Constrained alpha,alpha
      Dialkylated Amino Acids with Potent and Selective Activity at Human Melanocortin
      Receptors.
AB  - We report the development of macrocyclic melanocortin derivatives of MT-II and
      SHU-9119, achieved by modifying the cycle dimension and incorporating constrained
      amino acids in ring-closing. This study culminated in the discovery of novel
      agonists/antagonists with an unprecedented activity profile by adding pieces to
      the puzzle of the melanocortin receptor selectivity. Finally, the resulting 19-
      and 20-membered rings represent a suitable frame for the design of further
      therapeutic ligands as selective modulators of the melanocortin system.

PMID- 29660983
TI  - Microwave-Assisted Catalytic Combustion for the Efficient Continuous Cleaning of
      VOC-Containing Air Streams.
AB  - A microwave-heated adsorbent-reactor system has been used for the continuous
      cleaning of air streams containing n-hexane at low concentrations. Both, a single
      catalytic bed (PtY zeolite) and a double (adsorptive DAY zeolite + catalytic PtY
      zeolite) fixed-bed reactor configurations were studied under dry and humid
      conditions. The zeolites were selectively heated by short periodic microwave
      pulses that caused the desorption of n-hexane and its subsequent catalytic
      combustion. The double bed configuration was attractive because it allowed nearly
      the same performance with only half of the catalyst load. The operation was
      especially efficient under realistic humid gas conditions that favored more
      intense microwave absorption, producing a faster heating of the adsorptive and
      catalytic beds. Under these conditions, continuous gas cleaning could be achieved
      with short (3 min, 30 W) microwave heating pulses every 5 min.

PMID- 29660982
TI  - Facially Amphipathic Glycopolymers Inhibit Ice Recrystallization.
AB  - Antifreeze glycoproteins (AFGPs) from polar fish are the most potent ice
      recrystallization (growth) inhibitors known, and synthetic mimics are required
      for low-temperature applications such as cell cryopreservation. Here we introduce
      facially amphipathic glycopolymers that mimic the three-dimensional structure of
      AFGPs. Glycopolymers featuring segregated hydrophilic and hydrophobic faces were
      prepared by ring-opening metathesis polymerization, and their rigid conformation
      was confirmed by small-angle neutron scattering. Ice recrystallization inhibition
      (IRI) activity was reduced when a hydrophilic oxo-ether was installed on the
      glycan-opposing face, but significant activity was restored by incorporating a
      hydrophobic dimethylfulvene residue. This biomimetic strategy demonstrates that
      segregated domains of distinct hydrophilicity/hydrophobicity are a crucial motif
      to introduce IRI activity, which increases our understanding of the complex ice
      crystal inhibition processes.

PMID- 29660985
TI  - Facile On-Site Aqueous Pollutant Monitoring Using a Flexible, Ultralight, and
      Robust Surface-Enhanced Raman Spectroscopy Substrate: Interface Self-Assembly of
      Au@Ag Nanocubes on a Polyvinyl Chloride Template.
AB  - Aquatic ecosystems and human health have been seriously threatened by illegal
      discharge of wastewater, while simple and effective monitoring methods are still
      sparse. Here, we propose a facile method for on-site pollutant monitoring by
      surface-enhanced Raman spectroscopy with a novel substrate. This substrate is
      fabricated by interface self-assembly of Au@Ag nanocubes (NCs) on a
      simultaneously formed polyvinyl chloride (PVC) template, followed by coating with
      a thin Au film. The Au@Ag@Au-NCs/PVC film is flexible, ultralight, and robust and
      could float on the surface of water and firmly contact with water even under
      harsh environmental conditions. Moreover, the Au@Ag@Au-NCs/PVC film is
      translucent, allowing penetration of laser beams and enhancement of Raman
      signals. When thiram was used as a model contaminant in aqueous solution, a good
      linear relationship ( R2 = 0.972) was obtained over the range of 0.1-50 ppb with
      a detection limit of 0.1 ppb. Raman signals of thiram can be instantly and
      consecutively detected with the enhancement of the film in the simulated
      experiments, suggesting its possible use in the long run. Furthermore, the film
      can be easily regenerated by NaBH4 solution washing, which could reduce the
      operating cost. In summary, the Au@Ag@Au-NCs/PVC film has great potential in on
      site pollutant monitoring in aqueous environments with a portable Raman
      spectrometer.

PMID- 29660984
TI  - Chemically Induced Degradation of Anaplastic Lymphoma Kinase (ALK).
AB  - We present the development of the first small molecule degraders that can induce
      anaplastic lymphoma kinase (ALK) degradation, including in non-small-cell lung
      cancer (NSCLC), anaplastic large-cell lymphoma (ALCL), and neuroblastoma (NB)
      cell lines. These degraders were developed through conjugation of known
      pyrimidine-based ALK inhibitors, TAE684 or LDK378, and the cereblon ligand
      pomalidomide. We demonstrate that in some cell types degrader potency is
      compromised by expression of drug transporter ABCB1. In addition, proteomic
      profiling demonstrated that these compounds also promote the degradation of
      additional kinases including PTK2 (FAK), Aurora A, FER, and RPS6KA1 (RSK1).

PMID- 29660986
TI  - Gold nanoparticles functionalized with angiogenin-mimicking peptides modulate
      cell membrane interactions.
AB  - Angiogenin is a protein crucial in angiogenesis, and it is overexpressed in many
      cancers and downregulated in neurodegenerative diseases, respectively. The
      protein interaction with actin, through the loop encompassing the 60-68 residues,
      is an essential step in the cellular cytoskeleton reorganization. This, in turn,
      influences the cell proliferation and migration processes. In this work, hybrid
      nanoassemblies of gold nanoparticles with angiogenin fragments containing the 60
      68 sequence were prepared and characterized in their interaction with both model
      membranes of supported lipid bilayers (SLBs) and cellular membranes of cancer
      (neuroblastoma) and normal (fibroblasts) cell lines. The comparison between
      physisorption and chemisorption mechanisms was performed by the parallel
      investigation of the 60-68 sequence and the peptide analogous containing an extra
      cysteine residue. Moreover, steric hindrance and charge effects were considered
      with a third analogous peptide sequence, conjugated with a fluorescent
      carboxyfluorescein (Fam) moiety. The hybrid nanobiointerface was characterized by
      means of ultraviolet-visible, atomic force microscopy and circular dichroism, to
      scrutinize plasmonic changes, nanoparticles coverage and conformational features,
      respectively. Lateral diffusion measurements on SLBs "perturbed" by the
      interaction with the gold nanoparticles-peptides point to a stronger membrane
      interaction in comparison with the uncoated nanoparticles. Cell viability and
      proliferation assays indicate a slight nanotoxicity in neuroblastoma cells and a
      proliferative activity in fibroblasts. The actin staining confirms different
      levels of interaction between the hybrid assemblies and the cell membranes.

PMID- 29660987
TI  - Ecological Influences on Employees' Workplace Sedentary Behavior: A Cross
      Sectional Study.
AB  - PURPOSE:: The purpose of this study was to explore the relationship between
      ecological factors and occupational sedentary behavior (SB). DESIGN:: Cross
      sectional online survey. SETTING:: Participants were employees recruited from a
      large, public university in the Southeastern United States from August to
      November 2016. PARTICIPANTS:: The final sample included 527 (56% response rate)
      employees. MEASURES:: Data were collected through an 87-item survey using
      previously validated scales that assessed occupational SB, perceived behavioral
      control, barrier self-efficacy, self-regulation strategies, organizational social
      norms, office environment, and worksite climate. ANALYSIS:: One-way analysis of
      variance analyses were used to determine differences in occupational SB by
      demographic factors. A multivariate regression model was used to determine
      significant ecological determinants of occupational SB. RESULTS:: Mean SB was
      342.45 (standard deviation = 133.25) minutes. Significant differences in SB were
      found by gender, education, and employment classification. Barrier self-efficacy
      and workplace connectivity, which evaluates the spatial layout of the office
      setting that may impact mobility within the workplace, were significant
      predictors of SB in the multivariate model. CONCLUSION:: Results from this study
      provide new information regarding the potential impact of workplace barriers and
      connectivity on occupational SB. The findings from this study support the
      inclusion of intervention modalities to minimize workplace barriers and increase
      workplace connectivity to increase workplace mobility and decrease SB.

PMID- 29660989
TI  - Long-term outcome of stenting for atherosclerotic renal artery stenosis and the
      effect of angiographic restenosis.
AB  - BACKGROUND: Symptomatic renal artery stenosis (RAS) is mainly treated with
      pharmacological blood pressure control, sometimes with percutaneous transluminal
      renal angioplasty (PTRA). It is unclear if PTRA benefits these patients over
      time. PURPOSE: To determine long-term renal function, morbidity, and mortality in
      patients with symptomatic RAS treated with PTRA, and whether long-term outcomes
      are associated with angiographic restenosis. MATERIAL AND METHODS: Retrospective
      single-center, long-term follow-up of 57 patients with atherosclerotic RAS
      treated with PTRA with stent during 1995-2004 and investigated for restenosis
      with angiography after one year. Outcomes were retrieved from medical records and
      from mandatory healthcare registries. Mortality rates were related to expected
      survival in an age- and gender-matched population, using a life-table database.
      Surviving patients were assessed with blood pressures, laboratory tests, duplex
      ultrasonography, and radioisotope renography. RESULTS: Median follow-up was 11
      years 7 months. Major indications for PTRA were therapy-resistant hypertension
      and declining renal function. Angiographic restenosis at one year was found in 21
      of 57 patients (37%). Thirty-six patients (60%) died during follow-up. Main cause
      of death was cardiovascular events (54%). Mortality was significantly increased,
      and morbidity and healthcare utilization were high. Hypertension control during
      follow-up was stable with persistent need for anti-hypertensive medication, and
      renal function remained moderately reduced with no long-term difference between
      patients with vs. without restenosis. CONCLUSION: Long-term prognosis after PTRA
      for atherosclerotic RAS is dismal, with high mortality and morbidity and reduced
      renal function, despite maintained hypertension control. Restenosis does not
      appear to affect late outcome.

PMID- 29660988
TI  - Intervention Helps Family Caregivers of People With Dementia Attain Own Therapy
      Goals.
AB  - INTRODUCTION: Caregiver intervention studies typically assess whether
      participants attain general goals (eg, improved mental/physical health) but not
      their own individual goals. We used goal attainment scaling to evaluate whether
      participants of a telephone intervention based on cognitive behavioral therapy
      (CBT) attained their personal goals. We also evaluated treatment compliance and
      implementation. METHODS: A sample of 139 family caregivers of people with
      dementia received 12 telephone sessions over 6 months. Participants personal
      goals were specified during the first and second sessions. Participants and
      therapists assessed goal attainment at the end of the intervention. RESULTS:
      Nearly all participants reported meaningful improvements with regard to their
      personal goals. Specifically, 20.9% exceeded, 56.4% completely attained, and
      21.8% partially attained at least one of their personal goals. There was high
      agreement between self- and therapist ratings. Treatment compliance and
      implementation were highly satisfactory. CONCLUSIONS: The CBT telephone
      intervention successfully helped participants attain their personal goals.

PMID- 29660990
TI  - Novel Radiographic Assessment of the Cribriform Plate.
AB  - Background The cribriform plate (CP) is a common site of spontaneous
      cerebrospinal fluid (SCSF) leaks. Radiographic assessment of the anterior and
      lateral skull base has shown thinner bone in patients with SCSFs; however, prior
      assessment of the CP has required postmortem cadaver dissection. Objective To
      develop novel radiographic techniques to assess the anatomy of the CP. Methods
      Computed tomography (CT) scans were performed on cadaveric specimens. Bone
      density and anatomy of a predefined volume of interest of the posterior CP were
      assessed by two independent reviewers. CT assessment of olfactory foramina was
      also performed and validated using anatomic dissection of cadaver specimens.
      Results Interclass correlation coefficients (ICCs) for measuring the same volume
      of each CP was 0.96, confirming reproducible anatomic localization. Cadaver CPs
      had a mean Hounsfield units of 263, indicating a mix of bone and soft tissue, and
      ICC was 0.98, confirming reproducible radiographic measurements. Optimal CT
      estimates of bone composition of CPs averaged 85% (range 76% to 96%) compared to
      actual anatomic dissection which averaged 84% bone (range 74% to 91%, r = .690, P
      = .026). Conclusion Our novel, noninvasive CT method for assessing CP anatomy is
      reproducible and correlates with anatomic dissection assessing bone composition.
      The clinical implications of anatomic changes in the CP are an area for further
      study.

PMID- 29660991
TI  - Palliative Performance Scale Score at 1 Week After Palliative Care Unit Admission
      is More Useful for Survival Prediction in Patients With Advanced Cancer in South
      Korea.
AB  - BACKGROUND: The Palliative Performance Scale (PPS) is a useful prognostic index
      in palliative care. Changes in PPS score over time may add useful prognostic
      information beyond a single measurement. OBJECTIVE: To investigate the usefulness
      of repeated PPS measurement to predict survival time of inpatients with advanced
      cancer admitted to a palliative care unit (PCU) in South Korea. DESIGN:
      Prospective observational cohort study. SETTING/PATIENTS: 138 patients with
      advanced cancer admitted to a PCU in a university hospital in South Korea from
      June 2015 to May 2016. MEASUREMENTS: The PPS score was measured on enrollment and
      after 1 week. We used Cox regression analyses to calculate hazard ratios (HRs) to
      demonstrate the relationship between survival time and the groups categorized by
      PPS and changes in PPS score, after adjusting for clinical variables. RESULTS:
      There were significant differences in survival time among 3 groups stratified by
      PPS (10-20, 30-50, and >=60) after 1 week. A group with a PPS of 10 to 20 at 1
      week had the highest risk (HR: 5.18 [95% confidence interval, 1.57-17.04]) for
      shortened survival. On the contrary, there were no significant differences among
      these groups by initial PPS alone. Similarly, change in PPS was prognostic;
      median survival was 13 (10.96-15.04) days for those whose PPS decreased after 1
      week and 27 (10.18-43.82) days for those with stable or increased PPS ( P <
      .001). CONCLUSIONS: Measuring PPS over time can be very helpful for predicting
      survival in terminally ill patients with cancer, beyond a single PPS measure at
      PCU admission.

PMID- 29660993
TI  - A Multi-Targeted Quality Improvement Project of CT-Guided Procedure Start Times.

PMID- 29660992
TI  - Next of Kin's Notification of Patient's Death: A Qualitative and Quantitative
      Preliminary Analysis.
AB  - BACKGROUND: There are no published studies on notification of death by a next of
      kin to the treating medical staff. AIM: To explore the content and circumstances
      of death notifications by next of kin to the treating medical staff in a
      palliative home care unit. DESIGN: A cross-sectional study that combines
      qualitative and quantitative analysis. SETTING: Assessment of 153 telephone death
      notifications by a next of kin to the treating medical staff. RESULTS: The
      qualitative analysis of death notifications revealed 2 themes: direct and
      indirect death notifications. In direct notifications, death was portrayed by the
      notifier in direct and specific words such as death, the patient has died, or the
      patient is not alive. Indirect notifications included nonspecific or general
      descriptions of death such as breath cessation, it ended, or it's over or
      finished. Direct notifications tended to include specific requests from the
      medical staff and expressed acceptance and closure, while indirect notifications
      tended to include more general requests and expressed more panic, distress, or
      doubt in death. Although spouses were more likely to serve as the primary
      caregiver, the children or other family members were more likely to notify the
      treating staff. In 30% of the notifications, there was an element of doubt or
      uncertainty. Emotions were expressed in 20% of the notifications. Cessation of
      breathing was the most common physical sign mentioned. CONCLUSION: Medical staff
      members who receive notifications of death should expect and be prepared for the
      expression of varied emotions and doubts as an integral part of the notification.

PMID- 29660994
TI  - Providing Additional "Muscle" for Older Adults Through Optimal Influenza Vaccine
      Selection.
AB  - Immunization is the best strategy to protect individuals from influenza; however,
      older adults tend to respond less favorably to vaccines because of
      immunosenescence. The Centers for Disease Control and Prevention states that any
      licensed, recommended, and age-appropriate influenza vaccine may be used in older
      adults despite reasonable evidence suggesting that the high-dose and, to a lesser
      extent, the adjuvanted and recombinant influenza vaccines provide better
      protection than the standard-dose vaccines in this vulnerable population. In this
      era of precision medicine, clinicians can preferentially recommend these
      contemporary vaccines to equip their older patients with the best possible
      protection against influenza.

PMID- 29660995
TI  - Diagnostic Value of Nasal Cytology in Chronic Rhinosinusitis Assessed by a Liquid
      based Cytological Technique.
AB  - Back ground: Nasal cytology has generally been employed as a useful diagnostic
      tool in the differentiation of rhinopathies. Objective The aim of this study was
      to assess the extent and diagnostic value of inflammation of nasal and paranasal
      sinus mucosa in chronic rhinosinusitis patients by employing a combination of
      nasal brushings and a liquid-based cytological technique. Methods Forty-eight
      patients with chronic sinusitis and 20 control subjects without any sign of
      sinusitis undergoing endoscopic surgery, although not all underwent endoscopic
      sinus surgery, were recruited to the study. Nasal cytology samples were collected
      from all subjects using nasal brush and processed a liquid-based cytological
      technique for evaluation of total and differential inflammatory cell counts.
      Biopsies were also taken from the inferior turbinates from its anterior margin in
      all subjects and from identical lateral maxillary sinus mucosa in patients with
      chronic sinusitis during surgery and routinely processed for staining and
      evaluation of inflammatory cells. Results Total and individual inflammatory cell
      counts in nasal brushings were significantly correlated with the respective
      inflammatory cell counts in biopsies obtained from the inferior turbinate
      (eosinophils: r = .519 and P = .016; neutrophils: r = .540 and P = .012;
      lymphocytes: r = .540 and P = .011) but not in biopsies obtained from the
      maxillary sinus. No correlation was observed between the inflammatory cells in
      biopsies from the inferior turbinate and biopsies from the maxillary sinus. The
      liquid-based cytological technique showed higher sensitivity (94.1%), specificity
      (76.9%), and positive predictive value (84.2%) for inflammation in the inferior
      turbinates than for inflammation in the maxillary sinus (sensitivity = 63.4% and
      positive predictive value = 63.4%). Conclusion Nasal cytology evaluated by use of
      nasal brushings processed by a liquid-based cytological technique is likely to
      have higher diagnostic value for the inflammatory response in noninfectious
      rhinitis than in chronic rhinosinusitis.

PMID- 29660996
TI  - A case of hereditary coproporphyria with posterior reversible encephalopathy and
      novel coproporphyrinogen oxidase gene mutation c.863T>G (p.Leu288Trp).
AB  - A 21-year-old female had recurrent presentations to the emergency department with
      myalgia, vomiting, abdominal pain and subsequently developed generalized
      seizures. She was volume depleted with a plasma sodium of 125 mmol/L (reference
      interval: 135-145) and she had fluctuating hypertension. Acute porphyria was
      suspected and confirmed with raised urine porphobilinogen/creatinine ratio of
      12:4 MUmol/mmoL (reference interval < 1:5) and she was treated with intravenous
      haem arginate. Urinary porphyrin/creatinine ratio was 673 nmol/mmoL (reference
      interval <35) and faecal porphyrins 2430 MUmol/kg dry weight (reference interval:
      <200) were markedly elevated, with raised faecal CIII:CI ratio, consistent with
      acute coproporphyria. Diagnosis was confirmed by the demonstration of a novel
      missense variant in the coproporphyrinogen oxidase gene c.863T > G (p.Leu288Trp)
      predicted to be deleterious and which segregated with three other affected family
      members. Although CT head was normal, magnetic resonance imaging scan revealed
      symmetrical signal abnormalities and swelling in the parietal and occipital lobes
      consistent with posterior reversible encephalopathy. Over several days, her
      seizures ceased and sodium and blood pressure normalized. The aetiology of the
      acute porphyric attack was likely multifactorial with contributions from a recent
      viral illness and caloric deprivation. No drug precipitant was identified. We
      postulate that untreated hypertension played a key role in the development of
      posterior reversible encephalopathy. Early clinical suspicion and urine
      porphobilinogen testing are the key components in preventing morbidity and
      mortality in acute porphyrias.

PMID- 29660997
TI  - That '70%' claim again ....

PMID- 29660998
TI  - The challenge of improving the diagnostic yield from metanephrine testing in
      suspected phaeochromocytoma and paraganglioma.
AB  - Background Plasma-free metanephrines (PFM) or urinary fractionated metanephrines
      (UFM) are the preferred biochemical tests for the diagnosis of phaeochromocytoma
      and paraganglioma (PPGL). Borderline increased results should be followed up to
      either exclude or confirm diagnosis. Methods We extracted all PFM and UFM results
      reported by our laboratory over a six-month period from the laboratory
      information system. We categorized patients with borderline increased results
      according to whether follow-up testing had been performed as suggested in the
      initial laboratory report. Questionnaires were then sent to all requesting
      doctors and medical notes reviewed where available. Results Two hundred and four
      patients with borderline increased PFM or UFM were identified. Sixty-five (38.5%)
      of 169 patients with borderline increased PFM had a repeat test out of which 36
      were normal and 29 did not normalize. Of 35 patients with borderline increased
      UFM, 17 (48.6%) had subsequent PFM measurement, out of which 15 were normal.
      Questionnaires were returned to 106 (52%) patients. Of these, the most frequent
      indication for testing was hypertension ( n = 50); 15 patients had an incidental
      adrenal mass and two of these patients were diagnosed with a phaeochromocytoma.
      Conclusion Only 38% of patients with borderline increased PFM had a repeat PFM
      measurement. This was not significantly higher when compared with the 28% in a
      previous audit that we reported in 2010 ( P = 0.10). Forty-nine per cent of
      patients with a borderline increased UFM had a repeat UFM or PFM measurement.
      There remains a substantial possibility of missed detection of PPGL.

PMID- 29660999
TI  - A Community-Based Approach to HIV Prevention in Rural Guatemala.
AB  - BACKGROUND: HIV is one of the primary causes of death in Guatemala, and during
      the period 2005 to 2013, Guatemala exhibited a 95% increase in such deaths. HIV
      transmission rates are nearly 3 times higher among the indigenous Mayan
      population than nonindigenous Guatemalans. Guided by the community-based
      participatory research approach, this article demonstrates the iterative
      formative research process necessary to develop a deeper and more informed
      understanding of HIV prevention attitudes and behaviors in the priority
      population. This project extends preliminary formative research that demonstrated
      the applicability of the health belief model (HBM) in examining risk, stigma, and
      barriers and facilitators to condom use and HIV testing. METHOD: Using an
      integrated mixed-method design, data were collected from heterosexual adults 18-
      to 25 years old ( N = 250), including 50 in-depth interviews and 200 rapid
      assessment surveys. RESULTS: HBM concepts of risk and stigma were confirmed. Data
      also revealed low rates of condom negotiation and high embarrassment in
      purchasing and discussing condom use. Furthermore, data yielded very low uptake
      rates and reduced levels of comfort with getting tested. CONCLUSION: This
      research informs refinement of a culture-specific intervention prioritizing
      indigenous Mayans. We highlight how community-based research and engagement
      enhance community health promotion.

PMID- 29661000
TI  - Regulation of Clathrin-Mediated Endocytosis.
AB  - Clathrin-mediated endocytosis (CME) is the major endocytic pathway in mammalian
      cells. It is responsible for the uptake of transmembrane receptors and
      transporters, for remodeling plasma membrane composition in response to
      environmental changes, and for regulating cell surface signaling. CME occurs via
      the assembly and maturation of clathrin-coated pits that concentrate cargo as
      they invaginate and pinch off to form clathrin-coated vesicles. In addition to
      the major coat proteins, clathrin triskelia and adaptor protein complexes, CME
      requires a myriad of endocytic accessory proteins and phosphatidylinositol
      lipids. CME is regulated at multiple steps-initiation, cargo selection,
      maturation, and fission-and is monitored by an endocytic checkpoint that induces
      disassembly of defective pits. Regulation occurs via posttranslational
      modifications, allosteric conformational changes, and isoform and splice-variant
      differences among components of the CME machinery, including the GTPase dynamin.
      This review summarizes recent findings on the regulation of CME and the evolution
      of this complex process.

PMID- 29661002
TI  - Female Gynecologists and Their Birth Control Clinics: Eugenics in Practice in
      1920s-1930s China.
AB  - Yang Chao Buwei, the first Chinese translator of Margaret Sanger's What Every
      Girl Should Know, was the first female gynecologist to open up a birth control
      clinic in China. By the 1930s, other female gynecologists, like Guo Taihua, had
      internalized and combined national and eugenic concerns of race regeneration to
      focus on the control of women's reproduction. This symbiosis between racial
      regeneration and birth control is best seen in Yang Chongrui's integration of
      birth control into her national hygiene program. This article traces the efforts
      of pioneer gynecologists in giving contraceptive advice at their birth control
      clinics, which they framed as a humanitarian effort to ease the reproductive
      burden of working-class women. It also examines their connections with Sanger's
      international birth control movement, and their advocacy of contraception as
      practitioners, translators, and educators. The author argues that these Chinese
      female gynecologists not only borrowed, but adapted, Western scientific knowledge
      to Chinese social conditions through their writings and translations and in their
      clinical work.

PMID- 29661003
TI  - Outcomes Among Persons with HIV Following a Mental Health Admission: A Population
      Based Study.
AB  - To compare outcomes following psychiatric hospitalization between people with and
      without HIV. Population-based study of people with (n = 1,089) and without (n =
      280,888) HIV who were hospitalized for psychiatric illness between January 1,
      2006 and December 31, 2014. Overall, 9 (0.8%) people with HIV died within 30 days
      of discharge, compared with 3,710 (1.3%) HIV-negative individuals. Following
      multivariable adjustment, there was no difference in the risk of readmission or
      emergency department (ED) visits for psychiatric illness in the 90 days following
      discharge. Conversely, people with HIV were at higher risk of ED visits for
      substance use disorders and less likely to receive psychiatry follow-up during
      this period. HIV is associated with ED use for substance use disorders and less
      psychiatry follow-up within 90 days of hospital discharge for psychiatric
      illness. Interventions facilitating continuity of care following discharge are
      warranted.

PMID- 29661001
TI  - The 12 lead ECG rules the waves in acute cardiovascular care.

PMID- 29661005
TI  - Ethopathology and Civilization Diseases: Niko and Elisabeth Tinbergen on Autism.
AB  - The idea that some diseases result from a poor fit between modern life and our
      biological make-up is part of the long history of what historian of medicine
      Charles Rosenberg has called the "progress-and-pathology narrative." This article
      examines a key episode in that history: 1973 Nobel laureate Niko Tinbergen's use
      of an evolutionary framework to identify autism as a pathogenic effect of
      progress. Influenced by British psychiatrist John Bowlby's work, Tinbergen and
      his wife Elisabeth saw autistic children as victims of environmental stress
      caused mainly by mothers' failure to bond with their children and to protect them
      from conflicting situations. However, the author argues that their position was
      not "environmental." For them, autism was due to a failure of socialization but
      the mechanisms that explain that failure were established by biological
      evolution. Situating their views within the context of Niko's concern about the
      derailment of biological evolution by cultural evolution, this article shows that
      their ideas are of special significance for understanding the persistence of the
      view that civilization poses a risk to human health.

PMID- 29661004
TI  - Percutaneous Versus Surgical Revascularization for Left Main or Multivessel
      Coronary Artery Disease: Results From a Large-Scale Meta-Analysis in the Era of
      Drug-Eluting Stents.
AB  - The best treatment options for left main (LM) or multivessel coronary disease
      (MVD) are still debated. We performed a meta-analysis of randomized trials
      comparing percutaneous versus surgical revascularization for LM or MVD. Primary
      end point was overall mortality. Secondary end points were major adverse
      cardiovascular events, recurrent myocardial infarction, repeated
      revascularization, or stroke. A total of 8 randomized trials were included,
      involving 8694 patients, 50% undergoing percutaneous coronary intervention (PCI).
      At a mean follow-up of 39.7 months, mortality was 8.2% with no difference for PCI
      versus coronary artery bypass grafting (CABG; odds ratio [OR] 95% confidence
      interval [CI] = 1.18 [0.90-1.55]; P = .24, P for heterogeneity [ Phet] = .01).
      However, CABG was slightly favored for MVD (OR [95% CI] = 1.54 [1.12-2.13]; P =
      .008, Phet = .14 for PCI) whereas noninferior for LM disease (OR [95% CI] = 0.88
      [0.60-1.29]; P = .50, Phet = .10, P interaction = .03). A similar benefit with
      CABG was also observed in terms of repeated coronary revascularization, whereas
      PCI significantly reduced stroke. This meta-analysis shows that surgical coronary
      revascularization still offers advantages in survival and recurrent ischemic
      events compared to PCI using drug-eluting stents (DES) in MVD although burdened
      by an increased risk of stroke. In LM disease, CABG did not provide outcome
      benefits but was associated with a higher risk of stroke compared to PCI.
      Additional randomized trials are certainly needed with new-generation DES.

PMID- 29661008
TI  - Psychiatry in American Medical Education: The Case of Harvard's Medical School,
      1900-1945.
AB  - As American psychiatrists moved from the asylum to the private clinic during the
      early twentieth century, psychiatry acquired a growing presence within medical
      school curricula. This shift in disciplinary status took place at a time when
      medical education itself was experiencing a period of reform. By examining
      medical school registers at Harvard University, records from the Dean's office of
      Harvard's medical school, and oral histories, this paper examines the rise in
      prominence of psychiatry in medical education. Three builders of Harvard
      psychiatry - Elmer E. Southard, C. Macfie Campbell, and Harry C. Solomon -
      simultaneously sought to mark territory for psychiatry and its relevance. In
      doing so, they capitalized on three related elements: the fluidity that existed
      between psychiatry and neurology, the new venues whereby medical students gained
      training in psychiatry, and the broader role of patrons, professional
      associations, and certification boards, which sought to expand psychiatry's
      influence in the social and cultural life of twentieth-century America.

PMID- 29661009
TI  - To blind or not to blind? The search for a perfect peer review methodology.

PMID- 29661007
TI  - When Ernest Jones First Arrived in Toronto; or, Reappraising the Bruce Letter.
AB  - In July 1962, Toronto-based surgeon, Herbert Bruce, wrote a private and
      confidential letter to social worker and historian Cyril Greenland with some
      memories and impressions of Sigmund Freud's lifelong friend and biographer,
      Ernest Jones, in Toronto (1908-1913). In the letter, Bruce described Jones as a
      "sexual pervert." Despite Bruce's condemnation of Jones, historians and
      biographers have largely ignored his controversial memories of Jones in Toronto.
      The article traces how scholars have handled the existence of the Bruce letter,
      and the consequences for how this history has been understood. In the latter half
      of the article, the author considers how the existence of this letter might offer
      insights into how the Toronto medical establishment regarded Ernest Jones.

PMID- 29661006
TI  - The Healing Arts and Social Capital: The Paston Women of Fifteenth-Century
      England.
AB  - In late-medieval England, women's informal and gratis healthcare services helped
      them to accumulate and recompense social capital, which improved their families'
      and their own status and resources. Given the precariousness of health, special
      skills in the healing arts had a particular power to create a sense of gratitude
      and obligation. Evidence comes from the 15th-century letter collection of the
      Pastons, an ambitious gentry family from Norfolk. The Paston women appear both
      performing as healers in their kin networks and sending medical recipes and
      advice to their male and female relatives. Furthermore, seeking patronage at
      court, male relatives solicited medical secrets from the Paston women to pass
      along to their betters in an effort to advance their social status. This article
      argues that healthcare was a distinctly feminine form of participation in the
      Paston family's quest for social capital.

PMID- 29661011
TI  - Protein extraction from human anagen head hairs 1-millimeter or less in total
      length.
AB  - A simple method for extracting protein from human anagen (i.e., actively growing
      hair stage) head hairs was developed in this study for cases of limited sample
      availability and/or studies of specific micro-features within a hair. The
      distinct feature segments of the hair from one donor were divided lengthwise
      (i.e., each of ~200-400 MUm) and then pooled for three individual hairs to form a
      total of eight composite hair samples (i.e., each of ~1 mm or less in total
      length). The proteins were extracted, digested using trypsin, and characterized
      via nano-flow liquid chromatography tandem-mass spectrometry (nLC-MS/MS). A total
      of 63 proteins were identified from all eight protein samples analyzed of which
      60% were keratin and keratin-associated proteins. The major hair keratins
      identified are consistent with previous studies using fluorescence in situ
      hybridization and nLC-MS/MS while requiring over 400-8000-fold less sample. The
      protein extraction method from micro-sized human head hairs described in this
      study will enable proteomic analysis of biological evidence for cases of limited
      sample availability and will complement hair research. For example, research
      seeking to develop alternative non-DNA based techniques for comparing questioned
      to known hairs, and understanding the biochemistry of hair decomposition.

PMID- 29661010
TI  - Development of a cost effective and robust AlphaScreen(r) platform for
      application.
AB  - The use of AlphaScreen(r) detection has allowed researchers to examine a wide
      variety of molecular interactions for use in high-throughput screening. However,
      the cost of Alpha reagents can often be prohibitory for extended screening
      campaigns or for young investigators with limited funding. To reduce assay costs,
      many labs have focused on miniaturization, while there have been limited efforts
      to scale down Alpha reagents. Thus, we describe the optimization of an
      AlphaScreen detection platform by systematically reducing the Alpha reagents down
      to 2.5 MUg/ml beads, without compromising assay integrity. We demonstrate that
      reducing bead concentration reduces detection costs substantially while yielding
      robust statistics. We believe this simple new protocol will enhance the future
      utilization of AlphaScreen technology in high-throughput screening.

PMID- 29661012
TI  - Using synthetic oligonucleotides as standards in probe-based qPCR.
AB  - Real-time PCR (qPCR) is widely used in the life sciences. For quantifying DNA, a
      standard curve is required. Common methods for standard development are time
      consuming, costly, necessitate a specific skill set, and pose a contamination
      risk. Using a targeted synthetic oligonucleotide, such as a gBlocks(r) Gene
      Fragment, overcomes these drawbacks and provides researchers an accurate and
      quick solution to standard development. Here, we demonstrate that using a gBlocks
      fragment as a standard provides comparable sensitivity, reliability, and assay
      performance to a purified amplicon standard.

PMID- 29661015
TI  - Seeing is believing: structures and functions of biological molecules.
AB  - The ability to elucidate the structure and function of biological molecules holds
      great importance in a variety of domains. This includes prospects to tackle
      public health concerns, identification of new drug targets and therapeutic
      agents. In this issue of Tech News, Nawsheen Boodhun explores techniques used to
      understand macromolecules.

PMID- 29661016
TI  - In-Fusion(r) Cloning: Accuracy, Not Background.

PMID- 29661013
TI  - To find what's unique, stop averaging.
AB  - Written by Meenakshi Prabhune, PhD Will recent advances in single-cell analysis
      methods help us better understand and improve human health?

PMID- 29661014
TI  - A novel protocol for generating intact, whole-head spider cephalothorax tissue
      sections.
AB  - The diversity of spider behavior and sensory systems provides an excellent
      opportunity for comparative studies of the relationship between the brain and
      behavior. However, the morphology of spiders poses a challenge for histologists
      since the spider cephalothorax contains heterogeneous tissues and has both tough
      external and internal sclerotized regions. Unlike the heads of insects, the
      cephalothorax is highly pressurized, which can cause tissues to shift during
      processing and can reduce tissue cohesion in thick sections. This work describes
      a novel protocol for producing thick whole-head sections for morphological study
      by softening the exoskeleton and stabilizing friable tissue, without freezing or
      dehydration. It also presents an effective whole-head DiI staining method that
      uses minimal dehydration and highlights neural structures.

PMID- 29661020
TI  - Bio Spotlight-Citations.

PMID- 29661017
TI  - A novel orange-colored bimolecular fluorescence complementation (BiFC) assay
      using monomeric Kusabira-Orange protein.
AB  - The bimolecular fluorescence complementation (BiFC) assay was developed as a tool
      for the visualization of protein-protein interactions in living cells. To date,
      many types of BiFC systems with distinct colors have been developed. Most of the
      colors in the visible spectrum have been used in BiFC assays, with the exception
      of orange. In this study, we developed an orange-colored BiFC system using the
      Kusabira-Orange (KO) protein from the stony coral Fungia concinna. To obtain
      bright BiFC fluorescence, we compared fluorescence intensities of two monomeric
      KO variants (mKO1 and mKO2) and identified mKO2 as brighter than mKO1. The
      optimal split site for mKO2-based BiFC was defined by a comparative analysis of
      complementation efficiency and a signal-to-noise ratio. The resulting mKO2-based
      BiFC system successfully demonstrated protein dimerization in plant cells as a
      model experiment. The novel mKO2-based BiFC system will expand the possibility of
      multicolor BiFC analysis.

PMID- 29661018
TI  - Improved protein blotting efficiency with new Fast Wet Blotting technology.

PMID- 29661021
TI  - Dextran Sodium Sulfate for colitis animal model research.

PMID- 29661024
TI  - Surface engineered lipid nanoparticle-mediated site-specific drug delivery system
      for the treatment of inflammatory bowel disease.
AB  - The major challenge for the treatment of inflammatory bowel disease (IBD) is the
      incompetence to deliver the drug molecule selectively at the site of
      inflammation. Taking this into consideration, we proposed development of
      mannosylated nanostructured lipid carrier system (Mn-NLCs) for active targeting
      and site-specific delivery of budesonide to the inflamed tissues. The developed
      Mn-NLCs were characterized for particle size and size distribution, zeta
      potential, %entrapment efficiency, FTIR and TEM analysis. Furthermore, to ensure
      delivery of developed cargo to the colonic region, the Mn-NLCs were encapsulated
      using Eudragit(r) S100 coated pellets. The in vivo evaluation of developed system
      was performed by employing oxazolone colitis rat model. The average particle size
      of Mn-NLCs (301.7 +/- 2.88 nm) was found to be more than that of unconjugated
      NLCs (284.0 +/- 4.53 nm) with marginally reduced % entrapment efficiency (90.88
      +/- 3.86%). The in vitro cytotoxicity studies using J774A.1 cell line revealed
      that Mn-NLCs were non-toxic as compared to pure drug. The in vivo evaluation
      depicted that Mn-NLCs showed significant reduction in clinical activity scoring,
      macroscopic and microscopic indexing, colonic myeloperoxidase activity and
      inflammatory cytokines. In conclusion, the developed Mn-NLCs appear to be
      promising for the treatment of IBD by selectively targeting inflamed colonic
      region as compared to unconjugated nanoparticulate system.

PMID- 29661019
TI  - Real-time assessment of apoptosis and necrosis.

PMID- 29661023
TI  - TAK1 mediates apoptosis via p38 involve in ischemia-induced renal fibrosis.
AB  - Renal fibrosis is a common and characteristic symptom of chronic kidney disease
      (CKD). However, the molecular mechanisms of renal fibrosis remain elusive.
      Ischemia injury, as a major cause of AKI, deserves more attention in order to
      improve the knowledge of AKI-induced fibrosis. Transforming growth factor-beta
      (TGF-beta)-activated kinase 1 (TAK1) interacts directly with TGF-beta, which play
      a critical role in the progression of fibrosis. Therefore, the present study
      aimed to investigate the role of TAK1 in the pathogenesis of ischemia-induced
      renal fibrosis. Compared with mice in the vehicle group, mice intraperitoneally
      injected with TAK1 inhibitor were found to have lower serum creatinine, less
      tubular damage and more mild fibrosis following ischemia-induced AKI.
      Furthermore, inhibition of TAK1 reduced p38 phosphorylation, decreased expression
      of Bax and caspase 3 and apoptosis cells in kidneys of mice treated with IR
      induced AKI. Compared with vehicle-treated renal tubular epithelial cells, TAK1
      overexpression cells were found to have a higher apoptosis and fibrosis index
      level and p38 phosphorylation following hypoxia/reoxygenation (H/R) treatment.
      Furthermore, the p38 inhibitor combined with TAK1 overexpression verified the
      role of TAK1/p38 signaling pathway in apoptosis and fibrosis index level of renal
      tubular epithelial cells treated with H/R. Thus, our results show that TAK1 plays
      an important role in the pathogenesis of ischemia-induced renal fibrosis and may
      mediate p38-regulated cell apoptosis.

PMID- 29661026
TI  - Patient perceptions of injection devices used with dulaglutide and liraglutide
      for treatment of type 2 diabetes.
AB  - OBJECTIVE: Liraglutide and dulaglutide have demonstrated similar glycemic
      efficacy and safety. However, they differ in treatment administration and
      injection devices. The purpose of this study was to examine and compare patient
      perceptions of the injection devices used with liraglutide and dulaglutide.
      METHODS: Patients with type 2 diabetes treated with liraglutide or dulaglutide
      were recruited from across the US. Patients completed the Diabetes Injection
      Device Experience Questionnaire (DID-EQ) to rate their current injection device.
      Patients who had experience with both treatments also completed the Diabetes
      Injection Device Preference Questionnaire (DID-PQ) to report preferences between
      the two devices. ANCOVAs were conducted to compare DID-EQ scores between
      dulaglutide and liraglutide patients, while controlling for covariates.
      Descriptive statistics are presented for preferences reported on the DID-PQ.
      RESULTS: A total of 404 patients were recruited from 49 states (mean age = 60.7
      years; 54.0% female; 204 liraglutide; 200 dulaglutide). Mean DID-EQ item scores
      for both treatments were high, ranging from 3.48 to 3.90 on a 4 point scale.
      ANCOVAs found significantly higher scores for dulaglutide than liraglutide on DID
      EQ global items assessing ease of use (3.82 vs. 3.73, p = .040) and convenience
      (3.79 vs. 3.66, p = .004). Among the 58 patients who had used both devices, more
      patients reported a preference for the dulaglutide device than the liraglutide
      device on every item of the DID-PQ. CONCLUSIONS: High DID-EQ scores indicate
      positive perceptions of both the liraglutide and dulaglutide injection devices.
      The dulaglutide device was associated with slightly higher scores for ease of use
      and convenience than the liraglutide device.

PMID- 29661025
TI  - Self-efficacy as a predictor of patient-reported outcomes in adults with
      congenital heart disease.
AB  - OBJECTIVE: Self-efficacy is a known predictor of patient-reported outcomes in
      individuals with acquired diseases. With an overall objective of better
      understanding patient-reported outcomes in adults with congenital heart disease,
      this study aimed to: (i) assess self-efficacy in adults with congenital heart
      disease, (ii) explore potential demographic and medical correlates of self
      efficacy and (iii) determine whether self-efficacy explains additional variance
      in patient-reported outcomes above and beyond known predictors. METHODS: As part
      of a large cross-sectional international multi-site study (APPROACH-IS), we
      enrolled 454 adults (median age 32 years, range: 18-81) with congenital heart
      disease in two tertiary care centres in Canada and Switzerland. Self-efficacy was
      measured using the General Self-Efficacy (GSE) scale, which produces a total
      score ranging from 10 to 40. Variance in the following patient-reported outcomes
      was assessed: perceived health status, psychological functioning, health
      behaviours and quality of life. Hierarchical multivariable linear regression
      analysis was performed. RESULTS: Patients' mean GSE score was 30.1 +/- 3.3
      (range: 10-40). Lower GSE was associated with female sex ( p = 0.025), not having
      a job ( p = 0.001) and poorer functional class ( p = 0.048). GSE positively
      predicted health status and quality of life, and negatively predicted symptoms of
      anxiety and depression, with an additional explained variance up to 13.6%. No
      associations between self-efficacy and health behaviours were found. CONCLUSIONS:
      GSE adds considerably to our understanding of patient-reported outcomes in adults
      with congenital heart disease. Given that self-efficacy is a modifiable
      psychosocial factor, it may be an important focus for interventions targeting
      congenital heart disease patients' well-being.

PMID- 29661031
TI  - An Infant With Abnormal Upper Extremity Findings: A Case Report.

PMID- 29661029
TI  - Antimicrobial stewardship program in a Greek hospital: implementing a mandatory
      prescription form and prospective audits.
AB  - AIM: Antimicrobial stewardship programs (ASPs) are urgently needed for Greek
      hospitals in order to improve antibiotic usage. PATIENTS & METHODS: An ASP was
      implemented to a Greek hospital since February 2014. A mandatory order form was
      introduced for five antimicrobials; colistin, tigecycline, daptomycin, doripenem
      and linezolid. Prospective audits allowed for feedback to the prescribers without
      direct prescribing restriction. RESULTS: Antimicrobials' consumption at the
      baseline year and the 3 years of ASP implementation was 93.7, 99.1, 156.1 and
      105.9 defined daily doses/1000 patient days, respectively (p > 0.05). No
      statistically significant difference in isolation rates of multidrug-resistant
      pathogens was detected. CONCLUSION: Efforts are required to demonstrate the long
      term impact of our program on antibiotic prescription attitudes as well as
      antimicrobial resistance rates.

PMID- 29661030
TI  - Diagnostic accuracy of an identification tool for localized neuropathic pain
      based on the IASP criteria.
AB  - OBJECTIVE: Based on the clear neuroanatomical delineation of many neuropathic
      pain (NP) symptoms, a simple tool for performing a short structured clinical
      encounter based on the IASP diagnostic criteria was developed to identify NP.
      This study evaluated its accuracy and usefulness. METHODS: A case-control study
      was performed in 19 pain clinics within Spain. A pain clinician used the
      experimental screening tool (the index test, IT) to assign the descriptions of
      non-neuropathic (nNP), non-localized neuropathic (nLNP), and localized
      neuropathic (LNP) to the patients' pain conditions. The reference standard was a
      formal clinical diagnosis provided by another pain clinician. The accuracy of the
      IT was compared with that of the Douleur Neuropathique en 4 questions (DN4) and
      the Leeds Assessment of Neuropathic Signs and Symptoms (LANSS). RESULTS: Six
      hundred and sixty-six patients were analyzed. There was a good agreement between
      the IT and the reference standard (kappa =0.722). The IT was accurate in
      distinguishing between LNP and nLNP (83.2% sensitivity, 88.2% specificity),
      between LNP and the other pain categories (nLNP + nNP) (80.0% sensitivity, 90.7%
      specificity), and between NP and nNP (95.5% sensitivity, 89.1% specificity). The
      accuracy in distinguishing between NP and nNP was comparable with that of the DN4
      and the LANSS. The IT took a median of 10 min to complete. CONCLUSIONS: A novel
      instrument based on an operationalization of the IASP criteria can not only
      discern between LNP and nLNP, but also provide a high level of diagnostic
      certainty about the presence of NP after a short clinical encounter.

PMID- 29661022
TI  - Low Rates of Vaccination for Herpes Zoster in Older People Living With HIV.
AB  - Herpes zoster (HZ) occurs at a higher age-specific rate in people living with HIV
      (PLWH) than in the general population. We implemented a quality improvement study
      to assess herpes zoster vaccine (HZV) usage among PLWH, assess HZV usage after
      additional reminders/prompts, and identify barriers to HZV among older PLWH. HZV
      rates in PLWH were determined in six institutions with varying payment
      structures. For the intervention, Part 1, PLWH eligible for HZV at the University
      of Colorado were identified, and providers were notified of patient eligibility.
      In Part 2, in addition to provider notification, an order for HZV was placed in
      the patient's chart before a clinic appointment. HZ vaccination rates ranged from
      1.5% to 42.4% at six sites. Before the intervention, 21.3% of eligible University
      of Colorado patients had received HZV. An additional 8.3% received HZV with Part
      1 and 17.8% with Part 2 interventions. At completion, a total of 53.2% of
      eligible patients had received HZV through routine clinical care or the
      interventions. Insurance coverage concern was cited as a common reason for not
      receiving HZV. Minor adverse reactions occurred in 26.7% patients and did not
      require medical care. HZV coverage was low at a majority of sites. Clinical
      reminders with links to vaccination orders or preplaced vaccination orders led to
      improved HZV coverage in our clinic, but published guidelines for use of HZV in
      PLWH and improvement in logistic or insurance barriers to HZV receipt are
      paramount to improved HZV coverage.

PMID- 29661027
TI  - Social Determinants of Health and Preclinical Glycemic Control in Newly Diagnosed
      First-Episode Psychosis Patients.
AB  - BACKGROUND: The abnormally high incidence of disorders of glucose metabolism
      (DGM) in psychotic-spectrum disorders (PSD) has often been attributed to the side
      effects of antipsychotics and unhealthy lifestyles. The influence of social
      determinants of health has been largely ignored, despite ample evidence linking
      social adversity with both PSD and DGM. The aim of this study is to examine the
      influence of well-established social determinants of health on preclinical levels
      of glycated hemoglobin (HbA1c) in a sample of first-episode psychosis (FEP)
      patients. METHODS: In a sample of newly admitted FEP patients, univariate
      analyses were used to select the main predictors of HbA1c levels from the
      following social determinants of health: childhood trauma, immigrant background,
      visible minority status, and indices of social and material deprivation. The
      predictors identified in the univariate analyses were tested in multivariate
      linear regression models including age, sex, BMI, depression, and physical
      anergia (proxy of sedentary behaviour) as covariates. RESULTS: Univariate
      analyses identified visible minority status and childhood physical abuse as
      predictors of HbA1c. After controlling for covariates, minority status
      significantly predicted higher levels of glycated hemoglobin (beta = 0.23; P =
      0.01), and physical abuse had a marginally significant effect (beta = 0.23; P =
      0.06). Other predictors were not significantly associated. CONCLUSION: FEP
      patients from a visible minority or who were victims of childhood physical abuse
      have higher levels of HbA1c at admission compared with other patients. This might
      suggest an increase in risk for the development of future DGM. If confirmed,
      preventive strategies could be tailored for these groups.

PMID- 29661033
TI  - Dementia buddying as a vehicle for person-centred care? The performance of a
      volunteer-led pilot on two hospital wards.
AB  - Objectives To understand and explain whether a dementia buddies pilot introduced
      into two adjacent mental health hospital wards in England was achieving its aim
      of enhancing person-centred care. Methods The research used a cultural lens to
      evaluate the dementia buddies pilot. It comprised 20 in-depth semi-structured
      interviews with staff, volunteers and carers in the two wards where the pilot was
      introduced. Results The pilot's ability to deliver positive outcomes depended on
      its compatibility with the culture of the ward and it performed better in the
      ward where a person-centred culture of care already existed. In this ward, the
      pilot became a catalyst for improved experience among patients, carers and staff,
      whereas in the second ward, the pilot faced resistance from staff and achieved
      less. Conclusions This finding underlines the benefit of focusing on workplace
      culture to understand the performance of volunteer-led initiatives. It also shows
      that existing ward culture is a determining factor in the capacity for dementia
      buddy schemes to act as vehicles for culture change.

PMID- 29661028
TI  - Development of large-scale manufacturing of adipose-derived stromal cells for
      clinical applications using bioreactors and human platelet lysate.
AB  - In vitro expanded adipose-derived stromal cells (ASCs) are a useful resource for
      tissue regeneration. Translation of small-scale autologous cell production into a
      large-scale, allogeneic production process for clinical applications necessitates
      well-chosen raw materials and cell culture platform. We compare the use of
      clinical-grade human platelet lysate (hPL) and fetal bovine serum (FBS) as growth
      supplements for ASC expansion in the automated, closed hollow fibre quantum cell
      expansion system (bioreactor). Stromal vascular fractions were isolated from
      human subcutaneous abdominal fat. In average, 95 * 106 cells were suspended in
      10% FBS or 5% hPL medium, and loaded into a bioreactor coated with
      cryoprecipitate. ASCs (P0) were harvested, and 30 * 106 ASCs were reloaded for
      continued expansion (P1). Feeding rate and time of harvest was guided by
      metabolic monitoring. Viability, sterility, purity, differentiation capacity, and
      genomic stability of ASCs P1 were determined. Cultivation of SVF in hPL medium
      for in average nine days, yielded 546 * 106 ASCs compared to 111 * 106 ASCs,
      after 17 days in FBS medium. ASCs P1 yields were in average 605 * 106 ASCs (PD
      [population doublings]: 4.65) after six days in hPL medium, compared to 119 * 106
      ASCs (PD: 2.45) in FBS medium, after 21 days. ASCs fulfilled ISCT criteria and
      demonstrated genomic stability and sterility. The use of hPL as a growth
      supplement for ASCs expansion in the quantum cell expansion system provides an
      efficient expansion process compared to the use of FBS, while maintaining cell
      quality appropriate for clinical use. The described process is an obvious choice
      for manufacturing of large-scale allogeneic ASC products.

PMID- 29661035
TI  - Migraine mimicking stroke: What to do?

PMID- 29661037
TI  - Lysosomes and Brain Health.
AB  - One of the fundamental properties of the cell is the capability to digest and
      remodel its own components according to metabolic and developmental needs. This
      is accomplished via the autophagy-lysosome system, a pathway of critical
      importance in the brain, where it contributes to neuronal plasticity and must
      protect nonreplaceable neurons from the potentially harmful accumulation of
      cellular waste. The study of lysosomal biogenesis and function in the context of
      common and rare neurodegenerative diseases has revealed that a dysfunctional
      autophagy-lysosome system is the shared nexus where multiple, interconnected
      pathogenic events take place. The characterization of pathways and mechanisms
      regulating the lysosomal system and autophagic clearance offers unprecedented
      opportunities for the development of polyvalent therapeutic strategies based on
      the enhancement of the autophagy-lysosome pathway to maintain cellular
      homeostasis and achieve neuroprotection.

PMID- 29661036
TI  - When migraine mimics stroke: A systematic review.
AB  - BACKGROUND: Migraine with aura may mimic an acute ischemic stroke, so that an
      improper administration of thrombolytic treatment can expose migrainous patients
      to severe adverse effects. METHODS: This systematic review quantifies the
      relevance of migraine with aura among stroke mimics, checking for thrombolysis'
      safety in these patients. We reviewed the literature after 1995, distinguishing
      from studies dealing with stroke mimics treated with systemic thrombolysis and
      those who were not treated with systemic thrombolysis. RESULTS: Migraine with
      aura is responsible for 1.79% (CI 95% 0.82-3.79%) of all the emergency Stroke
      Unit evaluations and it represents 12.24% (CI 95% 6.34-22.31%) of stroke mimics
      in the group not treated with systemic thrombolysis. 6.65% (CI 95% 4.32-9.78%) of
      systemic thrombolysis administrations are performed in patients without an acute
      ischemic stroke. Migraine with aura is responsible for 17.91% of these (CI 95%
      13.29-23.71%). The reported rate of adverse events seems extremely low (0.01%).
      CONCLUSION: Migraine with aura is the third most common stroke mimic, following
      seizures and psychiatric disorders; it is responsible for about 18% of all
      improper thrombolytic treatments. Despite the absence of strong supporting data,
      thrombolysis in migraine with aura seems to be a procedure with an extremely low
      risk of adverse events.

PMID- 29661039
TI  - High-Fidelity Simulation of Pediatric Emergency Care: An Eye-Opening Experience
      for Baccalaureate Nursing Students.
AB  - Background Little attention has been given to in-depth examination of what high
      fidelity simulation is like for nursing students within the context of a
      pediatric emergency, such as a cardiopulmonary arrest. It is possible that such
      high-fidelity simulation could provoke in nursing students intense psychological
      reactions. Purpose The purpose of this study was to learn about baccalaureate
      nursing students' lived experience of high-fidelity simulation of pediatric
      cardiopulmonary arrest. Method Phenomenological methods were used. Twenty-four
      interviews were conducted with 12 students and were analyzed for themes. Results
      The essence of the experience is that it was eye-opening. The students found the
      simulation to be a surprisingly realistic nursing experience as reflected in
      their perceiving the manikin as a real patient, thinking that they were saving
      their patient's life, feeling like a real nurse, and feeling relief after
      mounting stress. It was a surprisingly valuable learning experience in that the
      students had an increased awareness of the art and science of nursing and
      increased understanding of the importance of teamwork and were feeling more
      prepared for clinical practice and wanting more simulation experiences.
      Conclusion Educators should capitalize on the benefits of high-fidelity
      simulation as a pedagogy, while endeavoring to provide psychologically safe
      learning.

PMID- 29661038
TI  - Valued activities and informal caregiving in stroke: a scoping review.
AB  - PURPOSE: Map the literature about valued activities and informal caregiving post
      stroke and determine the nature, extent, and consequences of caregivers' activity
      changes. METHODS: A scoping review was undertaken, searching Pubmed, Cinahl,
      PsycInfo, and Google Scholar. Two researchers independently identified relevant
      articles, extracted study characteristics and findings, and assigned codes
      describing the topics and outcomes. Using thematic analysis, the main study
      topics and study outcomes were described. RESULTS: The search yielded 662
      studies, 30 of which were included. These were mainly qualitative and cross
      sectional studies assessing caregivers' activity changes and related factors, or
      exploring caregivers' feelings, needs and strategies to deal with their activity
      challenges. Although caregivers often lost their social and leisure activities,
      which made them feel unhappy and socially isolated, we found no studies about
      professional interventions to help caregivers maintain their activities. Over the
      years, caregivers' activity levels generally increased. However, some caregivers
      suffered from sustained activity loss, which, in turn, relates to depression.
      CONCLUSION: Loss of valued activities is common for stroke caregivers. Although
      high-level evidence is lacking, our results suggest that sustained activity loss
      can cause stroke caregivers to experience poor mental health and wellbeing.
      Suggestions to help caregivers maintain their valued activities are presented.
      Implications for rehabilitation Not only stroke survivors but also their informal
      caregivers tend to lose their valued activities, such as their social and leisure
      activities. Although many caregivers manage to resume their valued activities
      over time, others suffer from sustained activity loss up to at least two years
      post stroke. Loss of valued activities in stroke caregivers can result in lower
      levels of wellbeing, depression, and social isolation. Rehabilitation
      professionals should screen stroke caregivers for activity loss and assist them
      in resuming their valued activities and maintaining their social contacts.

PMID- 29661040
TI  - Use of augmented fluoroscopic imaging during diagnostic bronchoscopy.
AB  - The single pulmonary nodule evaluation is a complex problem. In particular,
      attempts to biopsy peripheral nodules with bronchoscopy have been hampered by
      difficulty navigating to the correct airway and then confirming the instruments'
      proximity to the nodule. Virtual systems in use do not provide real-time feedback
      of a live image of the nodule in question. Fluoroscopy has traditionally offered
      limited assistance as often the nodule is not visible and provides no information
      on airways/pathways to the nodule. We describe the use of LungVision augmented
      fluoroscopy to aid in real-time navigation assistance to peripheral lung nodules.

PMID- 29661042
TI  - Identification and drawing of early concepts in children with autism spectrum
      disorder and children without disability.
AB  - This comparative study is a replication and extension of previous work related to
      children's drawings of early concepts. In all, 15 children with autism spectrum
      disorder (ASD) and 19 children without disability took part in the study, and
      were video recorded as they drew 10 early emerging concepts such as "eat" and
      "more." In a second task, the participants were asked to label Picture
      Communication Symbols conventionally used in augmentative and alternative
      communication (AAC) systems. Descriptive, correlational, and inferential
      statistics were used to analyze the data. The results were consistent with
      previous research for both groups. Across the 10 features coded, participants in
      both groups drew entire scenes and were more likely to draw complete
      representations of people. Identification of PCS was less than 25% for both
      groups. After a brief time delay, the participants were able to remember the
      names of their drawings; however, performance on this recall task was positively
      related to their age. The language scores of the participants without disability
      were associated with their use of isolated parts in drawings. Trends in the data
      suggest potential avenues for follow up with larger studies examining use of
      self, others, and entire scenes in children with ASD. Implications for therapy
      and future directions pertaining to symbolic understanding in children with ASD
      are discussed.

PMID- 29661034
TI  - The use of chitosan/PLA nano-fibers by emulsion eletrospinning for periodontal
      tissue engineering.
AB  - OBJECTIVE: In this study, nanofibrous scaffolds base on pure polylactic acid
      (PLA) and chitosan/PLA blends were fabricated by emulsion eletrospinning. By
      modulating their mechanical and biological properties, cell-compatible and
      biodegradable scaffolds were developed for periodontal bone regeneration.
      METHODS: Pure PLA and different weight ratios of chitosan nano-particle/PLA nano
      fibers were fabricated by emulsion eletrospinning. Scanning electron microscope
      (SEM) was performed to observe the morphology of nano-fibers. Mechanical
      properties of nano-fibers were tested by single fiber strength tester.
      Hydrophilic/hydrophobic nature of the nano-fibers was observed by
      stereomicroscope. In vitro degradation was also tested. Cells were seeded on nano
      fibers scaffolds. Changes in cell adhesion, proliferation and osteogenic
      differentiation were tested by MTT assay and Alizarin Red S staining. Reverse
      transcription-polymerase chain reaction (RT-PCR) assay was used to evaluate the
      expression of (Toll-like receptor 4) TLR4, IL-6, IL-8, IL-1beta, OPG, RUNX2 mRNA.
      RESULTS: It is shown that the mean diameter of nano-fibers is about 200 nm. The
      mean diameter of chitosan nano-particles is about 50 nm. The combination of
      chitosan nano-particles enhanced the mechanical properties of pure PLA nano
      fibers. By adding a certain amount of chitosan nano-particles, it promoted cell
      adhesion. It also promoted the osteogenic differentiation of bone marrow stem
      cells (BMSCs) by elevating the expression of osteogenic marker genes such as BSP,
      Ocn, collagen I, and OPN and enhanced ECM mineralization. Nonetheless, it caused
      higher expression of inflammatory mediators and TLR4 of human periodontal
      ligament cells (hPDLCs). CONCLUSION: The combination of chitosan nano-particles
      enhanced the mechanical properties of pure PLA nano-fibers and increased its
      hydrophilicity. Pure PLA nano-fibers scaffold facilitated BMSCs proliferation.
      Adding an appropriate amount of chitosan nano-particles may promote its
      properties of cell proliferation and osteogenic differentiation. The higher
      expression of inflammatory mediators caused by nano-fibers may be regulated via
      TLR4 pathway.

PMID- 29661043
TI  - Risks and consequences of travel burden on prophylactic granulocyte colony
      stimulating factor administration and incidence of febrile neutropenia in an aged
      Medicare population.
AB  - OBJECTIVE: Granulocyte colony-stimulating factors (G-CSFs) decrease the incidence
      of febrile neutropenia (FN) in patients receiving myelosuppressive chemotherapy.
      This study examines the impact patient travel burden has on administration of
      prophylactic G-CSFs and the subsequent impact on FN incidence. METHODS: Medicare
      claims data were used to identify a cohort of beneficiaries age 65+ with non
      myeloid cancers at high risk for FN between January 2012 and December 2014.
      Driving distance and time were calculated from patient residence ZIP code to the
      location of G-CSF and/or chemotherapy administration. Regression models were used
      to estimate the odds of G-CSF prophylaxis relative to patient driving distance
      and time, and odds of FN incidence relative to timing of G-CSF administration
      (optimal [days 2-4 after chemotherapy], sub-optimal [same day], or none).
      RESULTS: The 52,389 study patients had a mean age of 73.5 years, and were 82%
      female and 89% white race; 49% had female breast cancer, 12% lung cancer, 15%
      ovarian cancer, and 24% non-Hodgkin's lymphoma. Of these high FN risk patients,
      69% had at least one prophylactic G-CSF administration within at least one
      chemotherapy cycle. The percentage of patients receiving prophylactic G-CSFs in
      the first cycle was 56%. Median travel time was slightly longer for patients who
      did not receive G-CSFs and patients receiving short-acting vs long-acting G-CSFs.
      The odds of receiving no G-CSFs were 26-52% higher (depending on cancer type) for
      patients with a >80-min one-way travel time, compared to patients traveling <20
      min. Concurrently, the odds of FN (using a "narrow" definition) were 18-93%
      higher for patients who did not receive G-CSFs in the first cycle of
      chemotherapy. CONCLUSIONS: Travel burden, linked to clinic visits for G-CSF
      administration following myelosuppressive chemotherapy, is associated with sub
      optimal use of G-CSF prophylaxis, which may result in a higher incidence of FN.

PMID- 29661041
TI  - Prospective risk of osteoporotic fractures in patients with advanced chronic
      obstructive pulmonary disease.
AB  - Despite the high prevalence of osteoporosis in chronic obstructive pulmonary
      disease (COPD) patients, the fracture risk prediction tools are not routinely
      undertaken in the management of COPD. We quantified fracture risk using a
      validated risk prediction tool (Fracture Risk Assessment (FRAX(r))) and
      determined potential bone-protection treatment needs in patients with advanced
      COPD. The 10-year probability of major osteoporotic or hip fracture was
      calculated using the FRAX tool in a cohort of patients attending a hospital
      complex COPD service. Patients were identified to be at low, intermediate and
      high risk based on their FRAX scores, in accordance with the National
      Osteoporosis Guideline Group recommendations, to assess the number of patients
      requiring bone mineral density (BMD) testing or bone protection therapy. Two
      hundred forty-seven patients [mean (standard deviation (SD)) age 66 (9.1) years,
      26% current smokers, 40% women and median (interquartile range (IQR)) Medical
      Research Council (MRC) breathlessness scale 4 (0)] had a 10-year probability of
      9.5% (6.1) and 3.8% (4.6) for major osteoporotic and hip fractures, respectively.
      Thirty-six percentage of patients were identified to be at intermediate risk of
      developing fragility fracture, requiring BMD assessment, while 9% were at high
      risk, requiring treatment. Thirty-two percentage of high-risk patients were on
      bisphosphonates. The FRAX score can be used to assess the fracture risk within
      the COPD cohort and assist with decision-making about BMD measurement and
      provision of bone protection therapy.

PMID- 29661046
TI  - Diagnostic Accuracy of Tuning Fork Tests for Hearing Loss: A Systematic Review.
AB  - Objective (1) To determine the diagnostic accuracy of tuning fork tests (TFTs;
      Weber and Rinne) for assessment of hearing loss as compared with standard
      audiometry. (2) To identify the audiometric threshold at which TFTs transition
      from normal to abnormal, thus indicating the presence of hearing loss. Data
      Sources PubMed, Ovid Medline, EMBASE, Web of Science, Cochrane, and Scopus and
      manual bibliographic searches. Review Methods A systematic review of studies
      reporting TFT accuracy was performed according to a standardized protocol. Two
      independent evaluators corroborated the extracted data and assessed risk of bias.
      Results Seventeen studies with 3158 participants, including adults and children,
      met inclusion criteria. The sensitivity and specificity of the Rinne test for
      detecting conductive hearing loss ranged from 43% to 91% and 50% to 100%,
      respectively, for a 256-Hz fork and from 16% to 87% and 55% to 100% for a 512-Hz
      fork. The audiometric thresholds at which tests transition from normal to
      abnormal ranged from 13 to 40 dB of conductive hearing loss for the Rinne test
      and from 2.5 to 4 dB of asymmetry for the Weber test. Significant heterogeneity
      in TFT methods and audiometric thresholds to define hearing loss precluded meta
      analysis. There is high risk of bias in patient selection for a majority of the
      studies. Conclusion Variability exists in the reported test accuracy measurements
      of TFTs for clinical screening, surgical candidacy assessments, and estimation of
      hearing loss severity. Clinicians should remain mindful of these differences and
      optimize these techniques in specific clinical applications to improve TFT
      accuracy.

PMID- 29661047
TI  - Evolutionary history of genus Macrobrachium inferred from mitochondrial markers:
      a molecular clock approach.
AB  - Caridea, an infraorder of shrimps coming under Pleocyemata was first reported
      from the oceans before 417 million years followed by their radiation recorded
      during the Permian period. Hitherto, about 3877 extant caridean species were
      accounted within which one quarter constitute freshwater species. Freshwater
      prawns of genus Macrobrachium (Infraorder Caridea; Family Palaemonidae), with
      more than 240 species are inhabitants of diverse aquatic habitats like coastal
      lagoons, lakes, tropical streams, ponds and rivers. Previous studies on
      Macrobrachium relied on the highly variable morphological characters which were
      insufficient for accurate diagnosis of natural species groups. Present study
      focuses on the utility of molecular markers (viz. COI and 16S rRNA) for resolving
      the evolutionary history of genus Macrobrachium using a combination of phylogeny
      and timescale components. It is for the first time a molecular clock approach had
      been carried out towards genus Macrobrachium in a broad aspect with the
      incorporation of congeners inhabiting diverse geographical realms including
      endemic species M. striatum from South West coast of India. Molecular results
      obtained revealed the phylogenetic relationships between congeners of genus
      Macrobrachium at intra/inter-continental level along with the corresponding
      evolutionary time estimates.

PMID- 29661045
TI  - Recent approaches for targeted drug delivery in rheumatoid arthritis diagnosis
      and treatment.
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory disease with complex
      pathology characterized by inflammation of joints, devastation of the synovium,
      pannus formation, bones and cartilage destruction and often is associated with
      persistent arthritic pain, swelling, stiffness and work disability. In
      conventional RA therapy, because of short biological half-life, poor
      bioavailability, high and frequent dosing is required. Thereby, these anti-RA
      medications, which unable to selectively target affected zone, may cause severe
      side effects in extra-articular tissues. Today, nanotechnology has emerged as
      promising tool in the development of novel drug delivery systems for the
      treatment and diagnosis of intractable diseases such as RA. Active targeting in
      RA nanomedicine has also been introduced a successful way for facilitating
      specific uptake of therapeutic agents by the disease cells. In this review, it is
      attempted to describe various targeted drug delivery systems (localized and
      receptor-based) used for RA diagnosis and therapy. Then, we highlight recent
      developments related to various non-viral gene delivery systems for RA gene
      therapy.

PMID- 29661049
TI  - Academic Facility Utilization and Survival Outcomes in Adult Head and Neck
      Sarcomas: An NCDB Analysis.
AB  - Objectives To investigate clinicopathologic and treatment factors associated with
      survival in adult head and neck sarcomas in the National Cancer Database (NCDB).
      To analyze whether treatment settings and therapies received influence survival
      outcomes and to compare trends in utilization via an aggregated national data
      set. Study Design Prospectively gathered data. Setting NCDB. Subjects and Methods
      The study comprised a total of 6944 adult patients treated for a head and neck
      sarcoma from January 2004 to December 2013. Overall survival (OS) was the primary
      outcome. Results Increased age and tumor size, nodal involvement, and poorly
      differentiated histology had significantly reduced OS ( P < .001). Angiosarcoma,
      malignant nerve sheath tumor, malignant fibrous histiocytoma, osteosarcoma, and
      rhabdomyosarcoma histologic subtypes had significantly reduced OS, while
      liposarcoma, chondrosarcoma, and chordoma had improved OS ( P < .001).
      Utilization of surgical therapy was associated with improved OS, while positive
      surgical margins were associated with treatment at a community-based cancer
      program and had reduced OS ( P < .001). On multivariate analysis, treatment with
      radiation and/or chemotherapy was not significantly associated with OS; however,
      primary treatment with definitive chemoradiotherapy had significantly reduced OS.
      Patients treated at academic/research cancer programs (n = 3874) had
      significantly improved 5- and 10-year OS (65% and 54%, respectively) when
      compared with patients treated at community-based cancer programs (n = 3027; 49%
      and 29%; P < .001). The percentage utilization of these programs (56% vs 44%) did
      not change over the study period. Conclusion For adult head and neck sarcomas,
      treatment at an academic/research cancer program was associated with improved
      survival; however, despite increasing medical specialization, the percentage
      utilization of these programs for this rare tumor remains constant.

PMID- 29661044
TI  - DMEK versus DSAEK for Fuchs' endothelial dystrophy: A meta-analysis.
AB  - PURPOSE: To compare the safety and efficacy profiles of Descemet membrane
      endothelial keratoplasty (DMEK) and Descemet stripping automated endothelial
      keratoplasty (DSAEK) in adult patients with Fuchs' endothelial dystrophy.
      METHODS: Electronic database search on MEDLINE and CENTRAL from inception to
      August 2017. We included all comparative studies of DMEK versus DSAEK in patients
      with diagnosed Fuchs' endothelial dystrophy. Studies assessing rescue procedures
      were excluded to minimize bias. PRIMARY OUTCOME: mean difference in best
      corrected visual acuity (BCVA) at 3, 6, and 12 months postoperatively. SECONDARY
      OUTCOMES: rates of graft primary failure, rejection, and rebubbling; other graft
      related issues; mean difference in endothelial cell density; subjective visual
      outcomes; and patient satisfaction. RESULTS: A total of 10 retrospective studies
      of moderate methodological quality were included (n = 947 eyes, 646 DMEK). BCVA
      was better with DMEK at all evaluated time points (0.16 logMAR at 12 months)
      comparing to DSAEK (0.30 logMAR; p < 0.001). DMEK had a 60% lower rate of
      rejection (risk ratio (RR) 0.4, 95% CI (0.24, 0.67), p = 0.0005), but required
      more rebubblings (RR = 2.48, 95% CI (1.32, 4.64), p = 0.005). DMEK had more
      primary graft failures and less endothelial cell density loss, but statistical
      difference was not reached. More patients were satisfied after DMEK (odds ratio =
      10.29, 95% CI (3.55, 29.80), p < 0.0001). CONCLUSION: DMEK showed better
      postoperative results regarding BCVA, patient satisfaction, and graft-related
      issues. However, the small number of studies with short follow-up times and other
      methodological issues prompt us to interpret these results carefully.

PMID- 29661050
TI  - Healthcare resource use and costs associated with chronic kidney disease in US
      private insurance patients with multiple myeloma.
AB  - Objectives Within a median 1.2 years after patients have an initial diagnosis
      with multiple myeloma, up to 61% were diagnosed with renal impairment and 50%
      were diagnosed with chronic kidney disease. This study estimated economic burden
      associated with chronic kidney disease in multiple myeloma patients in the US.
      Methods In this retrospective cohort study, patients >=18 years old with >=1
      inpatient or >= 2 outpatient multiple myeloma diagnoses between 1 January 2008
      and 31 March 2015 were identified from MarketScan(r) Commercial and Medicare
      Supplemental Databases. Chronic kidney disease patients had >=1 diagnosis of
      chronic kidney disease Stages 1-5 (first chronic kidney disease diagnosis date =
      index date) on or after the first multiple myeloma diagnosis, and were propensity
      score matched 1:1 to multiple myeloma patients without chronic kidney disease,
      end-stage renal disease, dialysis, or other type of chronically impaired renal
      function. All patients had >=six-month continuous enrollment prior to index date
      and were followed for >=one month from index date until the earliest of inpatient
      death, end of continuous enrollment, or end of the study period (30 September
      2015). The per-patient per-year healthcare resource utilization and costs were
      measured during follow-up. Costs were total reimbursed amount in 2016 US dollars.
      Results A total of 2541 multiple myeloma patients with chronic kidney disease
      stages 1-5 and 2541 matched controls met the study criteria and were respectively
      69.3 and 69.6 years, 54.5% and 55.3% men, and had 572.2 and 533.4 mean days of
      follow up. Compared to controls, chronic kidney disease patients had
      significantly (all P < 0.001) higher proportions (57.1% vs. 32.1%) and frequency
      (1.2 vs. 0.5) of inpatient admissions, frequency of emergency room visits (5.1
      vs. 3.3), and total costs ($106,634 vs. $71,880). Sensitivity analyses found that
      patients with chronic kidney disease, end-stage renal disease, or dialysis had
      $78,455 ( P < 0.001) higher costs (per-patient per-year) than matched controls.
      Conclusions The economic burden associated with chronic kidney disease in
      patients with multiple myeloma was estimated to be between $34,754 and $78,455
      per-patient per-year. Given its substantial clinical and economic impact,
      preservation of renal function is important in multiple myeloma patient care.

PMID- 29661048
TI  - Evidence for a priming-based asymmetry in color identification.
AB  - Performance asymmetries in colour discrimination (or detection) between visual
      fields (VFs) are typically examined using mean or median reaction times and have
      tended to yield either a left VF advantage for all colours (i.e., lower reaction
      times) or no difference for any colour, although a right VF advantage has also
      been reported. We used a novel colour identification task in which participants
      simply identified the colour of a laterally presented rectangle (i.e., red or
      blue). A measure of priming effects - but not mean or median reaction times -
      revealed a VF * colour interaction across a pilot study and two experiments;
      priming for red versus blue stimuli was greater in the left VF and priming for
      blue stimuli was greater in the right versus left VF. Two plausible psychological
      explanations of this interaction are offered, including the potential generation
      of approach and avoidance motivations and different emotional responses to blue
      versus red stimuli. Future work will be needed, but the current findings indicate
      that the left and right hemispheres are differentially primed by different
      colours - the right hemisphere is primed to a greater extent by red stimuli, and
      the left hemisphere is primed more by blue stimuli.

PMID- 29661051
TI  - Association between inflammatory potential of diet and odds of gestational
      diabetes mellitus among Iranian women.
AB  - BACKGROUND: The possible relationship between diet-related inflammation and the
      risk of gestational diabetes mellitus (GDM) requires further investigation,
      especially in non-Western populations. We examined the association between
      dietary inflammatory index (DII) scores and GDM in a case-control study conducted
      in Iran. METHODS: This study included 122 GDM cases and 266 controls hospitalized
      for acute non-neoplastic diseases. Cases were pregnant women aged 18-40 years,
      who visited major general hospitals in different regions of Tehran. Pregnant
      women were screened for gestational diabetes between the 24th and 28th week of
      gestation with a 50-g, 1-hour glucose challenge test (GCT). Cases were diagnosed
      positive for GDM. Controls were pregnant women who had normal GCT test. DII
      scores were computed from dietary intake assessed by a previously validated 147
      item food frequency questionnaire. Logistic regression models adjusted age,
      gestational age, energy, exercise, BMI, smoking exposure, family history of
      diabetes, and history of multivitamin intake were used to estimate odds ratios
      (ORs) and 95% confidence intervals (CI). RESULTS: Subjects with higher DII scores
      (i.e. indicating a more proinflammatory diet) had a higher odd of GDM with the
      DII being used as both a continuous (OR = 1.20; 95% CI = 0.94-1.54) and as
      categorical (ORtertile 3vs1 = 2.10; 95% CI = 1.02-4.34, p-trend = .03).
      CONCLUSIONS: These results indicate that a proinflammatory diet, as evidenced by
      higher DII scores, is associated with increased odds of GDM among Iranian women.

PMID- 29661053
TI  - Differential Diagnosis of Sinonasal Lymphoma and Squamous Cell Carcinoma on CT,
      MRI, and PET/CT.
AB  - Objective The purpose of this study was to analyze computed tomography (CT) and
      magnetic resonance (MR) images and to evaluate the maximum standardized uptake
      value (SUV max) of positron emission tomography (PET)/CT parameters between
      sinonasal non-Hodgkin's lymphoma (NHL) and squamous cell carcinoma (SCC), knowing
      the imaging features that distinguish sinonasal NHL from SCC. Study Design Case
      series with chart review. Setting University tertiary care facility. Subjects and
      Methods We analyzed the features on CT, MR imaging, and PET/CT of 78 patients
      diagnosed with sinonasal NHL or SCC histopathologically. The CT (n = 34), MRI (n
      = 25), and PET/CT (n = 33) images of 39 patients with sinonasal NHL and the CT (n
      = 38), MR (n = 28), and PET/CT (n = 31) images of 39 patients with SCC were
      evaluated. The sinonasal NHL was diagnosed as natural killer/T-cell lymphoma (n =
      28) and diffuse large B-cell lymphoma (n = 11). Results Patients with sinonasal
      NHL had a larger tumor volume and higher tumor homogeneity than patients with SCC
      on T2-weighted and postcontrast MR images. Most of the sinonasal NHL and SCC
      showed a high degree of enhancement. The apparent diffusion coefficient (ADC)
      values and adjacent bone destruction were significantly lower in sinonasal NHL
      than in SCC. However, cervical lymphadenopathy, Waldeyer's ring involvement, and
      PET/CT SUV max showed no significant differences between sinonasal NHL and SCC.
      Conclusion CT and MR images of sinonasal masses showing a bulky lesion, marked
      homogeneity, and low ADC values without adjacent bone destruction are more
      suggestive of sinonasal NHL than SCC.

PMID- 29661057
TI  - Are the Motivational Effects of Autonomy-Supportive Conditions Universal?
      Contrasting Results Among Indians and Americans.
AB  - In Western theories of motivation, autonomy is conceived as a universal motivator
      of human action; enhancing autonomy is expected to increase motivation
      panculturally. Using a novel online experimental paradigm that afforded a
      behavioral measure of motivation, we found that, contrary to this prevailing
      view, autonomy cues affect motivation differently among American and Indian
      corporate professionals. Autonomy-supportive instructions increased motivation
      among Americans but decreased motivation among Indians. The motivational Cue *
      Culture interaction was extraordinarily large; the populations exhibited little
      statistical overlap. A second study suggested that this interaction reflects
      culturally specific norms that are widely understood by members of the given
      culture. When evaluating messages to motivate workers, Indians, far more than
      Americans, preferred a message invoking obligations to one invoking autonomous
      personal choice norms. Results cast doubt on the claim, made regularly in both
      basic and applied psychology, that enhancing autonomy is a universally preferred
      method for boosting motivation.

PMID- 29661058
TI  - Feeling Interpersonally Controlled While Pursuing Materialistic Goals: A
      Problematic Combination for Moral Behavior.
AB  - We created a life-goal assessment drawing from self-determination theory and
      achievement goal literature, examining its predictive power regarding immoral
      behavior and subjective well-being. Our source items assessed direction and
      energization of motivation, via the distinction between intrinsic and extrinsic
      aims and between intrinsic and extrinsic reasons for acting, respectively. Fused
      source items assessed four goal complexes representing a combination of direction
      and energization. Across three studies ( Ns = 109, 121, and 398), the extrinsic
      aim/extrinsic reason complex was consistently associated with immoral and/or
      unethical behavior beyond four source and three other goal complex variables.
      This was consistent with the triangle model of responsibility's claim that
      immoral behaviors may result when individuals disengage the self from moral
      prescriptions. The extrinsic/extrinsic complex also predicted lower subjective
      well-being, albeit less consistently. Our goal complex approach sheds light on
      how self-determination theory's goal contents and organismic integration mini
      theories interact, particularly with respect to unethical behavior.

PMID- 29661062
TI  - Poisoned Wine: Regulation, Chemical Analyses, and Spanish-French Trade in the
      1930s.
AB  - This paper describes the resources, scientific spaces, and experts involved in
      the study of a mass poisoning caused by the drinking of arsenic-contaminated wine
      exported from Spain to France in 1932. Local and international periodicals record
      the poisoning of 300 French sailors, and stressed the commercial implications of
      the case. We discuss the reports prepared by different experts (mainly
      physicians, agricultural engineers, and customs chemists). Their work was not
      limited to preparing technical publications or chemical analyses; they also
      actively defended the quality of their local wine, and played a major role in the
      discussions regarding the regulation of the international wine market in the
      1930s, when new standards regarding the analysis of wine were being considered.
      Curiously, this well-publicised case of mass poisoning did not have any
      noticeable consequences in the international regulation of wine. This absence of
      subsequent regulatory action and the role of experts are central topics of the
      paper.

PMID- 29661052
TI  - Older Adults' Internet Use for Health Information: Digital Divide by
      Race/Ethnicity and Socioeconomic Status.
AB  - Building upon literature suggesting low Internet use among racial/ethnic
      minorities and socioeconomically disadvantaged groups, this study examined how
      race/ethnicity and socioeconomic status (SES) influence the Internet use for
      health information, addressing both independent and interactive effects. Using
      data from 17,704 older adults in the California Health Interview Survey, logistic
      regression models were estimated with race/ethnicity (Whites, African Americans,
      Latinos, and Asians), SES index, and the interaction between race/ethnicity and
      SES index. Overall, approximately 40% of participants were Internet-users for
      health information. Direct effects of race/ethnicity and SES-and their
      interactions-were all found to be significant. Minority status combined with the
      lowest levels of SES substantially reduced the odds of using Internet for health
      information. Findings suggest the combination of racial/ethnic minority status
      and low SES as a source of digital divide, and provide implications for Internet
      technology training for the target population.

PMID- 29661056
TI  - (How) Does Initial Self-Control Undermine Later Self-Control in Daily Life?
AB  - Past research suggests that self-control lapses occur more frequently following
      demanding experiences in daily life. However, the reason for these effects is
      debated. Three studies were therefore conducted to better understand self-control
      lapses. Exploratory analyses were conducted in Study 1 to identify possible
      effects. Studies 2 and 3 evaluated these effects' reliability. Two patterns were
      identified. First, initial desire-goal conflict predicted later increases in
      subjective fatigue. This was in turn related to less effective self-control
      attempts. Second, initial self-control attempts also led participants to enact
      desires more frequently. This latter effect occurred even when (and perhaps
      especially when) those later desires were not resisted. In contrast, the strength
      model of self-control did not receive support, as initial self-control attempts
      did not affect the success of subsequent self-control attempts. These studies
      therefore suggest initial self-control does play an important role in producing
      later self-control lapses-just a different role than predicted by the strength
      model.

PMID- 29661054
TI  - Theory of Prejudice and American Identity Threat Transfer for Latino and Asian
      Americans.
AB  - Latinos and Asian Americans confront similar stereotypes as they are often
      presumed to be foreigners and subjected to American identity denial. Across six
      studies (total N = 992), we demonstrate that Latinos and Asians anticipate
      ingroup prejudice and specific types of subordination (e.g., American identity
      threat) in the face of outgroup threats that target one another (i.e., stigma
      transfer). The studies explore whether stigma transfer occurred primarily when
      shared Latino and Asian stereotype content was a salient component of the
      prejudice remark (e.g., foreigner stereotypes; Study 3), or when outgroup
      prejudice targeted a social group with shared stereotype content (Study 4),
      though neither appeared to substantively moderate stigma transfer. Minority group
      members who conceptualize prejudiced people as holding multiple biases (i.e., a
      monolithic prejudice theory) were more susceptible to stigma transfer suggesting
      that stereotype content is not necessary for stigma transfer because people
      assume that prejudice is not singular.

PMID- 29661063
TI  - Calcitonin Stewardship Strategies.
AB  - Despite being approved by the Food and Drug Administration for over 30 years,
      calcitonin salmon has seen a dramatic increase in acquisition cost over the last
      few years. Being commonly used for the treatment of hypercalcemia of malignancy,
      health systems must implement stewardship strategies in order to curtail usage.
      This review is intended to provide a background on calcitonin usage for
      hypercalcemia of malignancy and associated strategies to ensure appropriateness
      of utilization within health systems.

PMID- 29661032
TI  - Results From a Pilot Study of Handheld Vibration: Exercise Intervention Reduces
      Upper-Limb Dysfunction and Fatigue in Breast Cancer Patients Undergoing
      Radiotherapy: VibBRa Study.
AB  - PURPOSE: Although there is evidence that breast cancer patients benefit from
      exercising during treatment, exercising during radiotherapy and especially the
      effects on upper-limb dysfunctions have been infrequently assessed. Therefore, we
      primarily aimed to confirm our interventions' feasibility and secondarily aimed
      to affect upper-limb dysfunctions and fatigue. METHODS: Twenty-two breast cancer
      patients scheduled for radiotherapy were allocated to an intervention (IG) or a
      passive control group (CG) as they preferred. IG exercised 3*/week during 6 weeks
      of radiotherapy: cycling endurance, handheld vibration, and balance training. We
      documented adverse events and training compliance (feasibility) and assessed the
      range of shoulder motion (ROM), isometric hand grip strength, vibration sense on
      the first metacarpophalangeal joint of the affected upper limb, and fatigue.
      RESULTS: We observed no adverse events and a training compliance of 98 %. IG's
      ROM improved significantly (abduction: 11 degrees ; 95% confidence interval [CI]
      5 to 20; external rotation: 5 degrees , 95% CI 0 to 10), as did the hand grip
      strength (1.6 kg, 95% CI -0.6 to 3.1), while CG's ROM did not change. CG's
      vibration sense worsened (-1.0 points, 95% CI -1.5 to -0.5), while IG's remained
      stable. Changes in general fatigue levels between IG (-2.0 points, 95% CI -3.0 to
      -1.0) and CG (0.5 points, 95% CI -1.0 to 4.5) revealed significant differences (
      P = .008) Conclusions: Our intervention proved to be feasible and provides novel
      findings: it reduced fatigue levels and interestingly, handheld vibration
      exercises improved upper-limb function due to shoulder ROM, hand grip strength,
      and vibration sense.

PMID- 29661055
TI  - Messenger RNA Delivery for Tissue Engineering and Regenerative Medicine
      Applications.
AB  - The ability to control cellular processes and precisely direct cellular
      reprogramming has revolutionized regenerative medicine. Recent advances in in
      vitro transcribed (IVT) mRNA technology with chemical modifications have led to
      development of methods that control spatiotemporal gene expression. Additionally,
      there is a current thrust toward the development of safe, integration-free
      approaches to gene therapy for translational purposes. In this review, we
      describe strategies of synthetic IVT mRNA modifications and nonviral technologies
      for intracellular delivery. We provide insights into the current tissue
      engineering approaches that use a hydrogel scaffold with genetic material.
      Furthermore, we discuss the transformative potential of novel mRNA formulations
      that when embedded in hydrogels can trigger controlled genetic manipulation to
      regenerate tissues and organs in vitro and in vivo. The role of mRNA delivery in
      vascularization, cytoprotection, and Cas9-mediated xenotransplantation is
      additionally highlighted. Harmonizing mRNA delivery vehicle interactions with
      polymeric scaffolds can be used to present genetic cues that lead to precise
      command over cellular reprogramming, differentiation, and secretome activity of
      stem cells-an ultimate goal for tissue engineering.

PMID- 29661060
TI  - Mental Work Demands and Late-Life Cognitive Impairment: Results From the Shanghai
      Aging Study.
AB  - OBJECTIVE: The aim of this study is to explore the association between mental
      work demands (MWDs) and late-life cognition among Chinese older adults. METHOD:
      Data were drawn from the baseline of the Shanghai Aging Study. RESULTS: Among
      3,546 participants, the mean MWDs index of participants with dementia, mild
      cognitive impairment (MCI), and cognitive normal were 2.8 ( SD = 0.5), 2.8 ( SD =
      0.5), and 2.9 ( SD = 0.4), respectively. Mini Mental State Examination (MMSE)
      scores in group with low MWDs level decreased more dramatically by increasing age
      than that in groups with middle and high MWDs level ( p < .001). In a subgroup of
      participants with education >=6 years, we found a positive correlation between
      MWDs index and MMSE score after adjusting for gender, age, body mass index,
      income, living alone, smoking, drinking, anxiety, depression, heart disease,
      hypertension, diabetes, and APOE-epsilon4 (apolipoprotein), by generalized linear
      model analysis ( p < .001). DISCUSSION: Our results suggest that long-time mental
      work stimulation during adulthood would have potential benefits to late-life
      cognition.

PMID- 29661061
TI  - Correlation of Nasal Eosinophilia and Response after Nasal Provocation Test in
      Patients with Nonallergic Rhinitis.
AB  - Objectives We aimed to evaluate the relationship between nasal eosinophilia and
      nasal hyperresponsiveness to allergen extract. Study Design Retrospective chart
      review. Setting Academic tertiary rhinologic practice. Subjects and Methods We
      performed allergy tests (skin prick test and multiple allergosorbent test) and
      nasal cytology for 194 patients with rhinitis symptoms (76 males and 118 females;
      age, 11-69 years). According to the results, they were classified into 4 groups:
      group A (allergic rhinitis with eosinophilia, n = 26), group B (allergic rhinitis
      without eosinophilia, n = 77), group C (nonallergic rhinitis with eosinophilia
      syndrome, n = 20), and group D (nonallergic rhinitis without eosinophilia, n =
      71). We performed a nasal provocation test (NPT) using house dust mite extract
      and assessed the changes in symptoms and the decrease in acoustic parameters
      (total nasal volume and minimal cross-sectional area [MCA]). Results Patients in
      group C were more likely to have severe rhinorrhea and sneezing than those in
      group D ( P < .001). After NPT, group C had greater aggravation of nasal
      obstruction than group D ( P < .001). Group C also showed markedly greater MCA
      changes as compared with group D 15 minutes after the antigen challenge ( P =
      .002). There was significant correlation between the number of eosinophils and an
      increase in nasal obstruction ( r = 0.319, P = .0009), rhinorrhea ( r = 0.302, P
      = .0017), sneezing ( r = 0.219, P = .0241), change in the total nasal volume 15
      minutes after NPT ( r = 0.287, P = .0028), and change in the MCA 15 minutes ( r =
      0.322, P = .0008) and 30 minutes ( r = 0.250, P = .0098) after NPT. Conclusion In
      patients with NAR, nasal eosinophilia is associated with provocative response
      after NPT. Further research should be performed to elucidate the mechanisms that
      underlie this phenomenon.

PMID- 29661059
TI  - The smartphone in the memory clinic: A study of patient and care partner's
      utilisation habits.
AB  - Smartphones have potential as cognitive aids for adults with cognitive
      impairments. However, little is known about how patients and their care partners
      utilise smartphones in their day-to-day lives. We collected self-reported
      smartphone utilisation data from patients referred for neuropsychological
      evaluations (N = 53), their care partners (N = 44), and an Amazon Mechanical Turk
      control sample (N = 204). Patient participants were less likely to own a
      smartphone than controls, with increasing age associated with less utilisation of
      smartphone features in all groups. Of the patients who owned smartphones,
      spontaneous use of cognitive aid features (e.g., reminders and calendars)
      occurred on only a monthly-to-weekly basis; by comparison, patients reported
      utilising social/general features (e.g., email and internet) on a weekly-to-daily
      basis. Individuals referred for geriatric cognitive disorder evaluations were
      less likely to own and use smartphones than individuals referred for other
      reasons. Care partners reported using their smartphones more frequently than
      control group adults, with 55% of care partners endorsing utilising their device
      in caring for the patient. Building upon existing smartphone use habits to
      increase the use of cognitive aid features may be a feasible intervention for
      some patients, and including care partners in such interventions is encouraged.

PMID- 29661069
TI  - The Black Cloud Phenomenon in Hand Surgery.
AB  - BACKGROUND: The term black cloud for a surgeon is generally used to describe
      someone who is unusually busy compared with his or her counterparts, and it is a
      superstition that tends to pervade the medical world. The purpose of this study
      is to investigate whether black clouds exist in hand surgery. METHODS: We
      examined one academic year's worth of hand surgery-specific call at a level I
      trauma center and tabulated the number of hand-related patient transfers and add
      on cases per surgeon. Each surgeon was given a black cloud rating by the fellows
      who were in training that year. Correlations were made between the black cloud
      rating and the surgeons' call volume. RESULTS: There were 12 surgeons who shared
      365 days of hand call, and 5 of them are hand surgery fellowship trained. Those 5
      surgeons tended to be busier on their call days, with more cases added on
      overnight and the next day, and also had worse black cloud ratings than the 7 non
      hand fellowship trained surgeons. CONCLUSIONS: In regard to hand surgery, while
      true emergencies occur and require emergent intervention, how busy hand surgeons
      may be during call may be influenced by a variety of factors not related to their
      patients' problems but rather their daily schedules, their hospitals' ability to
      facilitate add-on cases, and their rapport with their fellow surgeons to share
      case loads.

PMID- 29661068
TI  - Correlation Between Radiological Parameters and Functional Outcomes in Patients
      Older Than 60 Years of Age With Distal Radius Fracture.
AB  - BACKGROUND: The relationship between radiographic and functional outcomes is
      controversial in the elderly. The objective of this study is to determine whether
      there is a correlation between functional outcome and acceptable distal radius
      fracture (DRF) alignment in patients older than 60 years of age. METHODS: This
      correlation study was carried out at the Central Metropolitan Health Service of
      Chile. A total of 180 patients diagnosed with extra-articular DRF, according to
      the AO classification, were prospectively recruited. Radiological parameters,
      including radial inclination, residual dorsal angulation, ulnar variance, and
      articular step-off, were evaluated to assess the results of orthopedic reduction.
      Functional outcome was assessed immediately following cast removal and again at
      the 6-month follow-up. The Disabilities of the Arm, Shoulder and Hand (DASH) and
      Patient-Rated Wrist Evaluation (PRWE) questionnaires were administered to assess
      upper extremity function, and the visual analog scale (VAS) was used to assess
      pain intensity. RESULTS: Only 68 patients (37.8%) showed acceptable DRF
      alignment. After cast removal, the correlations between alignment and the
      functional outcome measures were as follows: DASH 0.071 ( P = .546), PRWE 0.03 (
      P = .823), and VAS 0.12 ( P = .631). At the 6-month follow-up, the correlations
      between alignment and the functional outcome measures were as follows: DASH 0.029
      ( P = .768), PRWE 0.014 ( P = .895), and VAS 0.09 ( P = .614). CONCLUSIONS: There
      was no significant correlation between acceptable alignment according to
      radiological parameters and short- or medium-term functional outcome in patients
      older than 60 years with extra-articular DRF treated conservatively.

PMID- 29661064
TI  - Experience and confidence of final year veterinary students in performing
      desexing surgeries.
AB  - AIMS: To describe the level of experience and confidence of veterinary students
      in performing canine and feline desexing procedures at the end of their final
      clinical year. METHOD: A cross-sectional survey was conducted with veterinary
      students at Massey University in November 2017 after completion of their final
      clinical year. The questions included career plans after graduation, number of
      assisted and unassisted desexing procedures performed, approximate time to
      complete desexing surgeries, level of confidence with different aspects of
      desexing surgeries, what aspects of their desexing surgery training were most
      helpful, and what could be done to improve training in desexing surgical skills
      in veterinary school. RESULTS: The survey was completed by 70/95 (74%) students
      in their final clinical year. Among respondents, 55/70 (70%) had performed >2
      unassisted feline neuters before graduation. However 38/70 (54%) students had
      never performed an unassisted feline spay, 31/70 (44%) had never performed an
      unassisted canine neuter, and 44/70 (63%) students had never performed an
      unassisted canine spay. The median reported times to complete a feline neuter,
      feline spay, canine neuter, and canine spay were 9, 40, 30 and 60 minutes,
      respectively. The median level of confidence for these procedures were 9, 6, 7
      and 5 (on a scale from 1=least confident to 10=most confident), respectively. The
      reported time to complete procedures and the confidence in performing procedures
      did not change markedly with increasing total number of procedures performed.
      Students were most concerned about their ability to perform the desexing
      procedures in a reasonable amount of time and to prevent post-operative bleeding
      from occurring. Students were least concerned with their ability to manage post
      operative pain in patients and to select the appropriate suture material. Free
      text comments revealed that 62/70 (89%) students wanted more hands-on surgical
      experience prior to graduation. CONCLUSION AND CLINICAL RELEVENCE: Many students
      are currently completing veterinary school with limited experience and low
      confidence with performing routine canine and feline desexing procedures. Further
      research is needed to identify the most effective ways for addressing this issue
      within the constraints of the veterinary curriculum and teaching hospital
      resources.

PMID- 29661070
TI  - Scaphoid Cysts: Literature Review of Etiology, Treatment, and Prognosis.
AB  - BACKGROUND: Cystic lesions of the carpal bones are rare entities that are
      infrequently reported in the literature. Scaphoid intraosseous cystic lesions
      represent a rare subset of carpal bone cysts. This review aims to summarize the
      available evidence on the evaluation and treatment of scaphoid cystic lesions to
      help guide clinical management. METHODS: Systematic electronic searches were
      performed using PubMed, Ovid, and Embase databases. Studies included were graded
      for their risk of bias. Pooled descriptive statistics were performed on
      incidence, etiology, physical exam findings, treatment, and follow-up. RESULTS: A
      total of 38 patients representing 41 scaphoid cystic lesions were pooled from 27
      articles. Patients presented with wrist pain without fracture (n = 27),
      pathological fracture (n = 9), swelling only (n = 1), or were asymptomatic (n =
      4). Cystic lesions of the scaphoid were initially revealed on imaging with
      radiographs alone (n = 22), radiographs in combination with computed tomography
      (CT) (n = 10) or magnetic resonance imaging (n = 6), CT alone (n = 1), or using
      all 3 modalities (n = 2). Intraosseous ganglia were identified most frequently (n
      = 31), followed by "bone cyst-like pathological change" (n = 3), unicameral bone
      cysts (n = 2), aneurysmal bone cysts (n = 2), primary hydatid cysts (n = 2), and
      cystic like changes post fall (n = 1). Treatment modalities included curettage
      and bone graft (n = 39) or below-elbow cast (n = 2). On follow-up (average of
      21.3 months; n = 40), all patients improved clinically after treatment and were
      found to have full wrist range of motion without pain (n = 31), slightly reduced
      grip strength (n = 3), limited range of motion (n = 2), or persistent mild
      discomfort (n = 2). CONCLUSIONS: Scaphoid cystic lesions are most commonly
      intraosseous ganglia, but can include other etiologies as well. The main
      presenting symptom is radial wrist pain that usually resolves after treatment.
      The presence of intracarpal cystic lesions should be considered in the
      differential diagnosis of wrist pain.

PMID- 29661071
TI  - A Comparison of Image Quality and Radiation Exposure Between the Mini C-Arm and
      the Standard C-Arm.
AB  - BACKGROUND: The use of intraoperative fluoroscopy has become mandatory in osseous
      hand surgery. Due to its overall practicality, the mini C-arm has gained
      popularity among hand surgeons over the standard C-arm. This study compares image
      quality and radiation exposure for patient and staff between the mini C-arm and
      the standard C-arm, both with flat panel technology. METHODS: An observer-based
      subjective image quality study was performed using a contrast detail (CD)
      phantom. Five independent observers were asked to determine the smallest circles
      discernable to them. The results were plotted in a graph, forming a CD curve.
      From each curve, an image quality figure (IQF) was derived. A lower IQF equates
      to a better image quality. The patients' entrance skin dose was measured, and to
      obtain more information about the staff exposure dose, a perspex hand phantom was
      used. The scatter radiation was measured at various distances and angles relative
      to a central point on the detector. RESULTS: The IQF was significantly lower for
      the mini C-arm resulting in a better image quality. The patients' entrance dose
      was 10 times higher for the mini C-arm as compared with the standard C-arm, and
      the scatter radiation threefold. CONCLUSIONS: Due to its improved image quality
      and overall practicality, the mini C-arm is recommended for hand surgical
      procedures. To ensure that the surgeons' radiation exposure is not exceeding the
      safety limits, monitoring radiation exposure using mini C-arms with flat panel
      technology during surgery should be done in a future clinical study.

PMID- 29661076
TI  - She taught it, she role modeled it, and she lived it: A tribute to Theresa Marie
      Sullivan: November 9, 1960-March 20, 2018.

PMID- 29661073
TI  - Services, systems, and policies affecting mobility device users' community
      mobility: A scoping review: Services, systemes et politiques influencant la
      mobilite dans la communaute des utilisateurs d'aides a la mobilite : examen de la
      portee.
AB  - BACKGROUND: Opportunities to travel from one place to another in the community,
      or community mobility, are especially important for mobility device users'
      ability to participate fully in society. However, contextual challenges to such
      mobility exist. PURPOSE: This study summarizes the literature on existing
      community mobility barriers and facilitators of mobility device users created by
      services, systems, and policies as defined by the International Classification of
      Functioning, Disability, and Health (ICF). METHOD: Arksey and O'Malley's approach
      for scoping studies was used for the review. The extraction chart was organized
      following the ICF, and frequency counts were used to report the data. FINDINGS:
      The findings suggest that certain factors, such as transportation, open-space
      planning, and architecture and construction, influence community mobility
      opportunities. However, little attention has been paid to services, systems, and
      policies in the research literature, limiting the knowledge on the subject.
      IMPLICATIONS: Further research is needed to examine the relationship between
      specific services, systems, and policies and mobility device users' mobility
      within their communities.

PMID- 29661077
TI  - Primum non nocere : Reflexions d'une ergotherapeute a la retraite sur la
      fabrication d'ortheses et le principe de precaution.

PMID- 29661072
TI  - Using information communication technology to identify deficits in rural health
      care: a mixed-methods evaluation from Guatemala.
AB  - BACKGROUND: In August 2014, the Centre for the Studies of Equity and Governance
      in Health Systems (CEGSS) in Guatemala launched an online platform, which
      facilitates complaints about health services via text messages. The aim is to
      collect, systemise and forward such complaints to relevant institutions, and to
      create a data pool on perceived deficits of health care in rural Guatemala.
      OBJECTIVE: To evaluate if the online platform is an accepted, user-friendly and
      efficient medium to engage citizens in the reporting of health care deficiencies
      in Guatemala. METHODS: The general study design of this research was a mixed
      method approach including a quantitative analysis of complaints received and a
      qualitative exploration of the attitude of community leaders towards the
      platform. RESULTS: User statistics showed that a total of N = 228 messages were
      sent to the platform in the period August 2014-March 2015. The majority of
      complaints (n = 162, 71%) fell under the 'lack of drugs, equipment or supplies'
      category. The community leaders welcomed the platform, describing it as modern
      and progressive. Despite feedback mechanisms and methods to respond to complaints
      not yet being fully developed, many users showed a high intrinsic motivation to
      use the new tool. Others, however, were restrained by fear of personal
      consequences and distrust of the state's judicial system. Access to mobile
      phones, reception, and phone credit or battery life did not pose major obstacles,
      but the producing and sending of correctly formatted messages was observed to be
      difficult. CONCLUSION: The online platform paired with SMS technology appears to
      be a viable approach to collect citizens' complaints in health care and connect
      citizens with relevant institutions. Further studies should be conducted to
      quantify follow-up activities and the impact on local health care provision.

PMID- 29661081
TI  - Measuring Visualized Tendon Length in Peroneal Tendoscopy.
AB  - BACKGROUND: Despite multiple studies outlining peroneal tendoscopy, no study
      exists to evaluate how effective tendoscopy is at visualizing the peroneal
      tendons without missing a lesion. We sought to measure the length of the peroneal
      tendons that could be visualized using tendoscopy. METHODS: Ten fresh cadaveric
      specimens were evaluated using standard peroneal tendoscopy techniques. Peroneus
      longus and brevis tendons were pierced percutaneously with Kirschner wires at the
      edge of what could be seen through the camera. The tendon sheaths were then
      dissected and the distances from anatomic landmarks were directly measured.
      During zone 3 peroneus longus tendoscopy, a more distal portal site was created
      for the final 5 specimens. RESULTS: The peroneus brevis could be visualized
      through the entirety of zone 1 and up to an average of 19.5 mm (95% confidence
      interval, 16.5-22.5) from its insertion onto the base of the fifth metatarsal in
      zone 2. Peroneus longus could be visualized through the entirety of zones 1 and 2
      and up to an average of 9.7 mm from its insertion onto the base of the first
      metatarsal in zone 3. This distance was decreased significantly with a more
      distal portal. The muscle belly of peroneus brevis terminated an average of 1.8
      mm (-3.7 to 7.3) above the tip of the lateral malleolus. CONCLUSIONS: Despite
      limitations, these results suggest that the vast majority of the length of the
      peroneal tendons can be seen during routine peroneal tendoscopy. A more distal
      skin portal site may improve visualization of zone 3 of peroneus longus. CLINICAL
      RELEVANCE: This study confirms the ability of peroneal tendoscopy to see the
      entire tendon length with appropriate portal placement.

PMID- 29661075
TI  - Primum non nocere: Reflections from retirement regarding orthotic fabrication and
      the precautionary principle.

PMID- 29661083
TI  - Measuring Visualized Joint Surface in Hallux Metatarsophalangeal Arthroscopy.
AB  - BACKGROUND: Arthroscopy has been increasingly used to evaluate small joints in
      the foot and ankle. In the hallux metatarsophalangeal (MTP) joint, little data
      exist evaluating the efficacy of arthroscopy to visualize the articular surface.
      The goal of this cadaveric study was to determine how much articular surface of
      the MTP joint could be visualized during joint arthroscopy. METHODS: Ten fresh
      cadaveric foot specimens were evaluated using standard arthroscopy techniques.
      The edges of the visualized joint surface were marked with curettes and Kirschner
      wires; the joints were then surgically exposed and imaged. The visualized surface
      area was measured using ImageJ(r) software. RESULTS: On the distal 2-dimensional
      projection of the joint surface, an average 57.5% (range, 49.6%-65.3%) of the
      metatarsal head and 100% (range, 100%-100%) of the proximal phalanx base were
      visualized. From a lateral view of the metatarsal head, an average 72 degrees
      (range, 65-80 degrees) was visualized out of an average total articular arc of
      199 degrees (range, 192-206 degrees), for an average 36.5% (range, 32.2%-40.8%)
      of the articular arc. CONCLUSION: Complete visualization of the proximal phalanx
      base was obtained. Incomplete metatarsal head visualization was obtained, but
      this is limited by technique limitations that may not reflect clinical practice.
      CLINICAL RELEVANCE: This information helps to validate the utility of arthrosocpy
      at the hallux metatarsophalangeal joint.

PMID- 29661082
TI  - Endoscopic Resection of Different Types of Talocalcaneal Coalition.
AB  - BACKGROUND: The purpose of this study was to describe the technique of endoscopic
      resection of talocalcaneal coalition (TCC) by using 2 posterior portals and to
      report the outcomes of endoscopic resection of different types and sites of TCC.
      METHODS: An interventional prospective study was conducted on 20 feet in 18
      consecutive patients who were diagnosed by computed tomography to have TCC for
      which nonoperative treatment had failed and endoscopic resection was performed.
      The patients were divided into groups according to the site of the coalition
      (middle facet or posterior facet) and according to type (fibrous, cartilage, or
      bony). The mean follow-up period was 26 months (range, 6-36). RESULTS: The
      average preoperative American Orthopaedic Foot & Ankle Society (AOFAS) hindfoot
      score was 57.7 (range, 40-65), and the average preoperative visual analog scale
      (VAS) score was 7.8 (range, 6-8). The average postoperative AOFAS hindfoot score
      was 92.4 (range, 85-98; P < .01). The average postoperative VAS score was 2.4
      (range, 1-4). All patients showed no recurrence on postoperative lateral and
      Harris-Beath X-ray until the end of the study. CONCLUSIONS: Endoscopic resection
      of TCC was an effective and useful method for the treatment of talocalcaneal
      coalition. It provided excellent outcomes with no recurrence in this short-term
      study. Resection of the fibrous type had a better outcome than resection of
      cartilage and bony types. Endoscopic resection of the posterior coalition had a
      better outcome than resection of the middle coalition. LEVEL OF EVIDENCE: Level
      III, comparative study.

PMID- 29661092
TI  - Evaluation of fetal serum thiol/disulphide homeostasis in deliveries complicated
      by nuchal cord.
AB  - AIM: To investigate the serum thiol/disulphide homeostasis in deliveries
      complicated by nuchal cord (NC) and to compare the results with healthy
      deliveries (without NC). METHODS: This prospective controlled study included 48
      pregnant women complicated by NC and 48 similar gestational aged healthy pregnant
      women during labor. Fetal umbilical cord serum samples were collected during
      labor and the thiol/disulphide homeostasis was measured by using an automated
      assay method. The patients were followed up until end of the delivery and
      perinatal outcomes were recorded. RESULTS: Fetal umbilical cord native thiol,
      total thiol, and disulphide levels as well as disulphide/native thiol and
      disulphide/total thiol ratios are impaired in labor with the presence of NC.
      There were no statistically significant differences in terms of maternal and
      gestational age at delivery and maternal number of gravida and parity, fetal
      gender, fifth Apgar scores <7, mode of delivery and fetal birth weight between
      groups. The group of patients with NC had higher emergency C/S numbers indicated
      for fetal distress and lower first Apgar scores <7. There were no neonatal
      intensive care unit admissions among these babies. CONCLUSIONS: Maternal serum
      thiol/disulphide homeostasis reflect transient effects of NC during labor
      regardless of labor type. Vaginal delivery can be safely and successfully
      performed in pregnancies complicated with NC.

PMID- 29661086
TI  - Consequences of non-medical switch among patients with type 2 diabetes.
AB  - OBJECTIVE: This study aimed to describe real-world experiences following a non
      medical switch among adults with type 2 diabetes mellitus (T2DM) in the United
      States. METHODS: For this cross-sectional study, patients with T2DM (N = 451)
      provided data on demographics, and how a non-medical switch of their anti
      hyperglycemic agent (AHA) affected their general health, HbA1c levels and
      medication management, via an Internet-based survey. Patients self-reported their
      level of satisfaction with the original medication and emotional reactions to the
      non-medical switch. Patients who recently experienced a non-medical switch of
      their AHA(s) (n = 379) were asked about the consequences of switching and their
      satisfaction with the switch (vs. the original) medication. RESULTS: Patients
      most frequently reported feeling very/extremely frustrated, surprised, upset and
      angry in reaction to a non-medical switch. Patients were somewhat satisfied with
      their original medication. Between 20% and 30% of patients reported the non
      medical switch had a moderate/major effect on their general health, diabetes,
      mental well-being and control over their health. The blood glucose levels of
      recent switchers were somewhat/much worse (20.7%) and medication management was
      somewhat/much worse (12.9%) on the switch (vs. the original) medication. Some
      recent switchers reported old symptoms returning (7.7%) and experiencing new side
      effects (14.2%). CONCLUSIONS: Approximately one in five patients reported a
      moderate/major negative impact on their blood glucose level, diabetes, mental
      well-being, general health and control over their health following a non-medical
      switch. Findings suggest that a non-medical switch may have unintended negative
      health consequences and results in considerable burden across multiple domains
      for a sizeable minority of patients with T2DM.

PMID- 29661084
TI  - Understanding the use of NIV in ALS: results of an international ALS specialist
      survey.
AB  - OBJECTIVE: To identify common practices of noninvasive ventilation (NIV) use
      among ALS specialists and how they follow respiratory status in their patients.
      METHODS: A 25-item questionnaire on NIV indications/initiation was sent via
      SurveyMonkey(r) to ALS specialists identified through membership in NEALS (114
      sites in the US) and ENCALS (39 sites in Europe). Descriptive statistics and
      Cochran-Mantel-Haenszel test for general association were performed. RESULTS: In
      their initial evaluation, US and European specialists (n = 186) use upright
      forced vital capacity (FVC) most (92.8% vs 91.1%; p = 0.752). Upright FVC results
      are most important for US respondents when deciding to prescribe NIV; European
      respondents consider symptoms of orthopnea and/or dyspnea as most important.
      European respondents use overnight pulse oximetry (69.8% vs 7.9%; p < 0.001) and
      arterial blood gas analyses (62.8% vs 3.2%; p < 0.001) more than US respondents.
      Insurance regulations/national health care coverage impact NIV initiation more in
      the US than in Europe (70.0% vs 47.5%; p = 0.025). When asked if insurance/other
      financial constraints affects when they prescribe NIV, more US respondents
      answered positively (77.2% vs 15.4%; p < 0.001). In patients with no respiratory
      symptoms, most US specialists (68.3%) initiated NIV at VC <50% predicted;
      European responses showed greater variability. CONCLUSIONS: Given the impact of
      NIV on respiratory function and the importance of respiratory function to quality
      of life and survival, understanding differences that influence NIV prescribing is
      critical. This information may inform future study design and identify areas
      warranting additional research to develop best practices for NIV implementation.

PMID- 29661091
TI  - Nuanced Reporting of Fistulas in Laryngectomy Studies.
AB  - Pharyngocutaneous fistula is an important complication of laryngectomy and can
      vary significantly in severity. Many authors have advocated for the use of
      vascularized flaps (eg, pectoralis major) to reduce the risk of fistula.
      Prevention of small, self-limited fistulas may not be worth the morbidity of a
      vascularized flap in some cases. More nuanced analysis of fistula outcomes,
      stratified by severity, may enable better surgeon-patient decision making
      regarding the use of vascularized flaps in laryngectomy.

PMID- 29661088
TI  - Perceived Versus Actual Risk of Type 2 Diabetes by Race and Ethnicity.
AB  - Purpose The purpose of this study was to examine associations between perceived
      risk and actual risk of type 2 diabetes by race and/or ethnicity. Methods The
      study sample included 10 999 adults from the 2011 to 2014 National Health and
      Nutrition Examination Survey. Sociodemographic, clinical, and behavioral data
      were collected using interviews and physical examinations. Participants were
      asked if they felt at risk for diabetes or prediabetes and then asked the reasons
      why. Data analyses were conducted with SAS to properly analyze complex survey
      data. Results About 86% of the sample (n = 9496) answered the risk perception
      question for diabetes, and among those, 28.4% indicated having a high perceived
      risk. Among this subsample, 38.3% were identified as having an actual risk for
      prediabetes or diabetes according to the American Diabetes Association
      guidelines. Across all race groups, the most frequently reported risk factors
      participants believed to contribute to their risk for diabetes were family
      history of diabetes, obesity, and poor diet habits. When the percentage of
      participants with an actual risk factor who correctly perceived it as a risk
      factor was examined, fewer Asians correctly perceived weight status and physical
      activity level as a risk for diabetes in contrast to the other racial/ethnic
      groups. Conclusions Our study showed that when perception was compared to actual
      risks, associations differed statistically by race. It will be essential to
      discuss their risk perception to proper screening for diabetes and relevant
      lifestyle modifications to prevent and delay the onset of diabetes.

PMID- 29661095
TI  - The effect of early relearning on sensory recovery 4 to 9 years after nerve
      repair: a report of a randomized controlled study.
AB  - : Twenty patients randomized to early sensory relearning (nine patients) or
      traditional relearning (11 patients) were assessed regarding sensory recovery 4
      to 9 years after median or ulnar nerve repair. Outcomes were assessed with the
      Rosen score, questionnaires, and self-reported single-item questions regarding
      function and activity. The patients with early sensory relearning had
      significantly better sensory recovery in the sensory domain of the Rosen score,
      specifically, discriminative touch or tactile gnosis and dexterity. They had
      significantly less self-reported problems in gripping, clumsiness, and fine motor
      skills. No differences were found in questionnaires between the two groups. We
      conclude that early sensory relearning improves long-term sensory recovery
      following nerve repair. LEVEL OF EVIDENCE: I.

PMID- 29661098
TI  - Predicting emergence from a disorder of consciousness using the Coma Recovery
      Scale-Revised.
AB  - This study explored the utility of the Coma Recovery Scale-Revised (CRS-R) in
      predicting emergence from a disorder of consciousness, using a sample of veterans
      who were treated at one of the five Veterans Affairs (VA) polytrauma
      rehabilitation centre sites in an Emerging Consciousness programme. Participants
      (N = 70) included both combat and non-combat active duty military personnel and
      veterans who sustained either a severe traumatic brain injury, or anoxic brain
      injury and were considered to have a disorder of consciousness at the time of
      admission. Patient information was retrospectively collected from electronic
      medical records from one of the VA polytrauma rehabilitation centre sites.
      Receiver Operator Characteristic models were utilised to explore "cut-off scores"
      for predicting emergence using the CRS-R. Results showed that week-three scores
      on the CRS-R were more accurate in determining whether a veteran would emerge
      from a disorder of consciousness. Limitations, including a limited sample size
      are explored, along with implications and recommendations for future research and
      clinical practice.

PMID- 29661102
TI  - Essential Tremor: More Than a Motor Disorder?

PMID- 29661090
TI  - Are disease severity, sleep-related problems, and anxiety associated with work
      functioning in patients with obstructive sleep apnoea?
AB  - PURPOSE: To examine whether Obstructive Sleep Apnoea severity, sleep-related
      problems, and anxiety are associated with work functioning in Obstructive Sleep
      Apnoea patients, when controlled for age, gender and type of occupation. To
      investigate whether anxiety moderates the associations between sleep-related
      problems and work functioning. MATERIALS AND METHODS: We included 105 Obstructive
      Sleep Apnoea patients (70% male; mean age 46.62 +/- 9.79 years). All patients
      completed the Pittsburgh Sleep Quality Index, the Epworth Sleepiness Scale, the
      Beck Anxiety Inventory, and the Work Role Functioning Questionnaire-2.0. RESULTS:
      Obstructive Sleep Apnoea-severity, poor nighttime sleep quality, and anxiety were
      univariately associated with impaired work functioning. Multivariate analyzes
      revealed that poor perceived sleep quality was more strongly associated with work
      functioning than sleep efficiency and daily disturbances. Anxiety was strongly
      associated with impaired work functioning. After adding anxiety, the explained
      variance in work functioning increased from 20% to 25%. Anxiety moderated the
      association between low and medium levels of nighttime sleep quality problems and
      work functioning. CONCLUSIONS: Poor perceived sleep quality and anxiety were
      strongly associated with impaired work functioning in Obstructive Sleep Apnoea
      patients. These findings may help to optimize management, standard treatment, and
      work functioning in people with Obstructive Sleep Apnoea when confirmed in
      longitudinal studies. Implications for Rehabilitation Studies show an impairment
      of functional status, including work functioning, in obstructive sleep apnea
      patients. Aside from physical disorders, obstructive sleep apnea patients often
      experience mental problems, such as anxiety. As many people with obstructive
      sleep apnea are undiagnosed, our results demonstrate to employers and healthcare
      professionals the need to encourage patients for obstructive sleep apnea
      screening, especially in the situation of impaired work functioning, increased
      anxiety, and poor sleep quality. The associations between obstructive sleep
      apnea, sleep and anxiety might increase the awareness of health professionals
      towards optimizing diagnostic accuracy and standard treatment.

PMID- 29661094
TI  - An investigation of PIK3CA mutations in isolated macrodactyly.
AB  - Somatic PIK3CA mutations may relate to pathogenesis of isolated macrodactyly. We
      set up to test the association between PIK3CA mutations with isolated
      macrodactyly in order to establish a more accurate and molecular mechanism-based
      diagnosis and classification. DNA extracted from affected tissues in 12
      individuals with isolated macrodactyly was tested for PIK3CA mutation using
      targeted Sanger DNA sequencing. Ten patients had macrodactyly in the foot and two
      in the hand. Nine of the 12 patients were found to carry a low-level, mosaic
      PIK3CA mutation. The mutations identified, p.His1047Arg, p.His1047Leu,
      p.Glu545Lys, and p.Glu542Lys, are codons frequently mutated in cancers. Among all
      tissues tested, adipose had the highest mutation detection rate, followed by
      nerve and skin. Our results indicate that a high proportion of isolated
      macrodactyly patients carry a pathogenic PIK3CA mutation. Affected adipose, nerve
      and skin tissues are ideal for PIK3CA mutation analysis.

PMID- 29661096
TI  - Employer attitudes toward hiring persons with disabilities in Armenia.
AB  - PURPOSE: The purpose of this two-part study was to provide input into a strategy
      to improve employment opportunities for persons with disabilities in Armenia.
      BACKGROUND: Employment rates for persons with disabilities in Armenia have been
      variously reported between eight and 21%, much below the general employment rate
      of 82%. METHOD: First, a Participatory Action Research process led to the
      development of a 15 item self-report measure - the Perceived Barriers to
      Employing Persons with Disabilities Scale - which was administered to 158
      employers. Second, respondent data were examined to determine psychometric
      properties of the scale and to inform strategic recommendations for policy
      development. FINDINGS: Exploratory factor analysis resulted in the removal of 6
      items, leaving a 9 item scale. Responses produced a multidimensional scale
      clustering around 2 factors. The first of these, structural issues, was
      principally informed by employer perceptions of limited skill levels of persons
      with disabilities, high costs associated with employing persons with
      disabilities, and the lack of accessibility within facilities. The second factor,
      social issues, was informed by employers' anticipation of negative reactions of
      coworkers, customers and supervisors toward persons with disabilities entering
      the workforce. Employers also indicated a belief that persons with disabilities
      with skills should be entitled to work. DISCUSSION AND CONCLUSION: Results of
      this study suggest that attitudes of Armenian employers toward people with
      disabilities, and subsequent hiring decisions, are partly informed by perceptions
      of the negative reactions of others within the workplace. This finding disagrees
      with studies from other jurisdictions, which generally consider that these
      attitudes are principally informed by perceived skills deficits on the part of
      people with disabilities. These results would support the development of employer
      focused information and awareness campaigns designed to address both of these
      factors. Implications for Rehabilitation Employment rates for people with
      disabilities are much below those of the general population. Research indicates
      that employer attitudes contribute significantly to the employment success of
      people with disabilities. A recent employer survey in Armenia indicates that
      these attitudes are influenced by a perception that others within the workplace
      do not accept people with disabilities. Vocational counseling and training
      programs, and employer awareness interventions, may be more effective if this
      influence on employer attitudes is addressed.

PMID- 29661106
TI  - Editor's Letter.

PMID- 29661099
TI  - miR-125b Contributes to Ovarian Granulosa Cell Apoptosis Through Targeting
      BMPR1B, a Major Gene for Sheep Prolificacy.
AB  - Bone morphogenetic protein receptor 1B (BMPR1B) is a major gene for ovine
      ovulation rate and litter size, which plays a crucial role in follicle
      development. However, its role and regulation in the ovine granulosa cells (GCs)
      are unclear. Here, we showed that silencing of BMPR1B enhanced cell apoptosis,
      whereas overexpression of BMPR1B inhibited cell apoptosis in the ovine GCs.
      Luciferase reporter assays revealed that BMPR1B is a target of miR-125b, and miR
      125b reduced BMPR1B messenger RNA and protein levels in the ovine GCs by directly
      binding to the 3' untranslated region of the ovine BMPR1B gene. Furthermore, miR
      125b enhanced cell apoptosis by attenuating BMPR1B in the ovine GCs. Our data
      demonstrated that BMPR1B is an important factor in the ovine GC function in vitro
      and targeted by a specific regulator miR-125b.

PMID- 29661097
TI  - Qualitative evaluation of how a virtual dementia experience impacts medical and
      pharmacy students' self-reported knowledge and attitudes towards people with
      dementia.
AB  - Objectives It is important for healthcare professional students to understand the
      experience of people with dementia, their family, and their carers. Despite
      person-centred educational policies, current curriculums may not adequately
      prepare students to meet the needs of people with dementia. This study
      qualitatively evaluated the impact of a virtual dementia experience on medical
      and pharmacy students' self-reported knowledge and attitudes towards people with
      dementia. Methods Ten focus groups were conducted with 29 medical and 24 pharmacy
      students in September and October 2016. All students had undertaken a
      multisensory virtual dementia experience designed to simulate the cognitive and
      perceptual difficulties faced by people with dementia. Focus groups were used to
      evaluate the virtual dementia experience in terms of perceived usefulness,
      suggestions for improvement, and ability to inform students' understanding of
      dementia-friendly environments. Focus groups were audio-recorded and analysed via
      a thematic approach. Results The virtual dementia experience was described as
      useful and impactful, and students suggested how it could be more tailored
      towards their learning needs, such as via incorporating hospital, medical, and
      pharmacy-specific scenarios and opportunities for role play. Additionally,
      students explained how dementia-friendly communication techniques could be used
      in their future practice and provided strategies to optimise dementia-friendly
      characteristics of current work environments. Conclusion A virtual dementia
      experience improved student self-reported knowledge and attitudes towards people
      with dementia.

PMID- 29661107
TI  - Implementation of Health Information Exchange at the Pima County Adult Detention
      Complex: Lessons Learned.
AB  - Successful transition of patients between health care entities is difficult.
      Historically, the process of transitioning individuals through the corrections
      system with regard to health care was made even more challenging by the
      limitation of paper records. Recently, the advent of electronic medical records
      has improved health care nationwide. The use of health information exchange (HIE)
      systems in areas such as emergency medicine has also impacted patient outcomes.
      To date, this technology has not been used in the corrections system. Semi
      structured interviews were conducted with 12 correctional health care
      professionals, corrections staff, and public health entities to evaluate the
      novel implementation of HIE at a local correctional facility. This article
      describes the challenges and successes that occurred during the implementation
      and their implications for successful implementations in the future.

PMID- 29661104
TI  - Effect of micro-roughening of poly(ether ether ketone) on bone marrow derived
      stem cell and macrophage responses, and osseointegration.
AB  - Poly(ether ether ketone) (PEEK) has emerged as a candidate to replace metal
      implants because of its satisfactory mechanical properties, radiolucency, and
      lack of metal allergy. However, PEEK lacks osseointegration ability limiting its
      clinical applications. To overcome this problem, we prepared PEEK with a micro
      rough surface using the sandblast method to modulate its osseointegration
      property; the sandblast method is simple, cost-effective, and is already applied
      to clinical metal implants. The surface roughness of the sandblasted PEEK was
      about 2.3 MUm, whereas that of mirror-polished PEEK was 0.06 MUm. Rat bone marrow
      derived mesenchymal stem cells (RMSCs) showed higher proliferation, osteocalcin
      (OC) expression and bone-like nodule formation on micro-roughened PEEK compared
      with those cultured on mirror-polished PEEK, suggesting that micro-roughening
      facilitated RMSCs proliferation and differentiation. The micro-roughened surface
      slightly mitigated secretion of inflammatory C-C motif chemokine 2 (CCL-2) from
      lipopolysaccharide (LPS)-stimulated macrophages, but not of tumor necrosis factor
      alpha (TNFalpha) and interleukin-6 (IL-6). Finally, to compare osseointegration,
      specimens were implanted in rat femur bone marrow cavities, and then the pull-out
      force was measured. The pull-out force of micro-roughened PEEK was about four
      times higher than that of the mirror-polished PEEK. These results showed that
      micro-roughening of PEEK using the sandblast method was able to improve
      osseointegration, partly through elevating proliferation and differentiation of
      RMSCs.

PMID- 29661108
TI  - Journal of Correctional Health Care.

PMID- 29661109
TI  - Prevalence and Risk Factors for Methicillin-Resistant Staphylococcus aureus
      (MRSA) Infections in Custodial Populations: A Systematic Review.
AB  - : Methicillin-resistant Staphylococcus aureus (MRSA) in prisons can result in
      serious morbidity and death. We reviewed rates and risk factors for MRSA
      infection in custody, searching Medline, EMBASE, and CINAHL databases. Between
      1997 and 2015, 17 studies reported MRSA skin and soft tissue infections (SSTIs),
      with four case reports of MRSA non-SSTI (necrotizing pneumonias, brain abscess,
      and epiduritis). Significant associations with MRSA SSTI were found: MRSA
      colonization, previous skin infection, sharing soap or personal items, SSTI
      presenting as an abscess or furuncle, younger age, non-Caucasian, overweight,
      communal laundering, infrequent handwashing, lower hygiene score.
      RECOMMENDATIONS: early identification, isolation, and treatment of skin
      infections at admission; education on maintaining skin integrity and presenting
      early with skin infections; increasing hygiene by not sharing items and
      encouraging handwashing; improved handling and disinfection of communal
      laundering; influenza vaccination for all prisoners and staff; and population
      based longitudinal studies including younger detainees.

PMID- 29661100
TI  - Progesterone-Induced miR-145/miR-143 Inhibits the Proliferation of Endometrial
      Epithelial Cells.
AB  - Our previous study showed that progesterone (P4) can specifically regulate the
      expression of some microRNAs (miRNAs) in endometrial epithelium. In the present
      study, we verified the P4-dependent expression of miR-145/miR-143 in endometrial
      epithelial cells, explored the regulative mechanism of the P4 receptor (PR), and
      investigated their effects on the proliferation of endometrial epithelial cells.
      Our results showed that P4 can induce the expression of miR-145/143 in
      endometrial epithelial cells by acting on the PR A subtype. P4-induced miR
      145/143 can inhibit the expression of cyclin D2 by binding to cyclin D2 mRNA
      3'UTR. It can also inhibit cell proliferation in mouse endometrial epithelium by
      arresting the cell cycle during the G1-S checkpoint. Furthermore, miR-145 and miR
      143 can inhibit the proliferation of human endometrial cancer cells. In
      conclusion, P4-induced miR-145/miR-143 is an important regulator in the
      proliferation of endometrial epithelial cells, and it can also inhibit the
      proliferation of human endometrial cancer cells. Our study indicates miRNAs are
      important mechanism of P4 in inhibiting the proliferation of endometrial
      epithelial cells. And these miRNAs are potential candidates for the diagnosis of
      endometrial cancer and therapeutic targets.

PMID- 29661110
TI  - Alteration of gait parameters in a mouse model of surgically induced knee
      osteoarthritis.
AB  - PURPOSE: Joint pain is the most common symptom of osteoarthritis (OA); however,
      its mechanism remains unclarified. The present study investigated hindlimb motion
      during locomotion on the treadmill using a three-dimensional (3D) motion analysis
      system with high-speed cameras to evaluate whether this method can be used as an
      indication of joint pain in a mouse model of surgically induced OA. METHODS: We
      resected the medial meniscus and medial collateral ligament in 8-week old C57BL/6
      male mice and performed locomotion recording 6 months post-operatively.
      Additionally, we performed the same recording after oral administration of the
      selective cyclooxygenase-2 inhibitor to determine whether alteration of the
      parameters were associated with joint pain. RESULTS: OA development,
      characterized by cartilage degeneration and osteophyte formation, was markedly
      enhanced in the OA group. There was no significant difference between the sham
      and OA groups in basic gait parameters, including stance duration, swing duration
      and gait cycle. However, when we divided the gait cycle into four phases and
      calculated the joint ranges of motion in each phase, the range of motion of the
      knee joint during the stepping-in phase and the swing duration were significantly
      decreased in the OA group. These significant differences between the sham and OA
      groups were diminished by the oral administration of a selective cyclooxygenase-2
      inhibitor to the OA group. CONCLUSION: The present method may be useful to
      evaluate joint pain in experimental mice and contribute to elucidating the
      molecular mechanisms of pain in the OA knee joint in combination with genetically
      modified mice.

PMID- 29661087
TI  - Allylpyrocatechol attenuates methotrexate-induced hepatotoxicity in a collagen
      induced model of arthritis.
AB  - The cornerstone of treatment for rheumatoid arthritis is low dose methotrexate
      (MTX), but its use is limited by concerns regarding its potential for
      hepatotoxicity. Allylpyrocatechol (APC), a phytoconstituent sourced from leaves
      of Piper betle demonstrated antioxidant, anti-inflammatory, and antiarthritic
      properties. The present study aimed to evaluate the combined effect of APC and
      MTX on limiting progression of lipopolysaccharide accelerated collagen-induced
      arthritis, along with reduction of MTX-induced hepatic damage. A collagen-induced
      arthritis (CIA) model was established by immunising Sprague-Dawley rats with
      bovine collagen type II (CII) and lipopolysaccharide, followed by a booster dose
      of CII on day 15. Rats from days 11-27 were administered APC (20 mg/kg),
      methotrexate (1.5 mg/kg), or a combination of MTX and APC. The combinatorial
      therapy of APC and MTX significantly improved the parameters of arthritis as
      evident from the reduction in paw oedema and arthritic score and was endorsed by
      radiological and histopathological changes. This combination prevented the rise
      in levels of proinflammatory cytokines, tumour necrosis factor (TNF-alpha), and
      interleukin 6 (IL-6). Furthermore, unlike MTX-monotherapy, the APC-MTX
      combination decreased the associated cachexia, splenomegaly, and oxidative
      stress. Importantly, the hepatic damage mediated by MTX monotherapy was
      effectively attenuated by the inclusion of APC. Taken together, antioxidants such
      as APC when combined with MTX not only potentiated the antiarthritic effect but
      importantly alleviated the MTX-induced hepatic damage, thus endorsing its
      effectiveness in preventing progression of articular diseases such as rheumatoid
      arthritis.

PMID- 29661111
TI  - Anatomic total shoulder arthroplasty with posterior capsular plication versus
      reverse shoulder arthroplasty in patients with biconcave glenoids: A matched
      cohort study.
AB  - PURPOSE: To compare the outcomes of total shoulder arthroplasty (TSA) with
      posterior capsule plication (PCP) and reverse shoulder arthroplasty (RSA) in
      patients with primary osteoarthritis, posterior subluxation, and bone loss (Walch
      B2). PATIENTS AND METHODS: All shoulders undergoing anatomic TSA with PCP were
      retrospectively identified (group 1, G1) and compared to shoulders undergoing RSA
      (group 2, G2) for Walch B2 osteoarthritis. There were 15 patients in G1 (mean
      (SD) age and follow-up of 70.5 (7.5) years and 42.8 (18.4) months, respectively)
      and 16 patients in G2 (mean (SD) age and follow-up of 72.6 (5.4) years and 35.1
      (14.2) months, respectively). RESULTS: Both groups had substantial improvements
      in pain and function. In G1, results were excellent in 80% and satisfactory in
      20%, compared to 81% and 6% in G2, respectively ( p = 0.2). The mean (SD)
      American Shoulder and Elbow Surgeons score was 91.2 (6.7) and 80.3 (14.3) in G1
      and G2, respectively ( p = 0.08). The mean Simple Shoulder Test score was 10.6 in
      G1 and 8.5 in G2 ( p = 0.01). There were no reoperations in either group, but G1
      had seven postoperative complications. CONCLUSIONS: The outcomes of TSA with PCP
      are comparable to RSA in patients with osteoarthritis and biconcave glenoids.
      However, TSA leads to more complications while RSA leads to lower functional
      outcomes.

PMID- 29661112
TI  - Osteoporotic effect on bone repair in lumbar vertebral body defects in a rat
      model.
AB  - INTRODUCTION: The number of patients who suffered from osteoporotic vertebral
      fractures is increasing. Osteoporosis has been reported to affect the healing
      process using long bone models. However, few studies have reported using
      vertebrae. In this study, we created a bone defect in the anterior part of
      vertebral body in ovariectomized rat and evaluated the healing process. METHODS:
      Fifty-six 12-week old Sprague Dawley rats were divided into ovariectomy (OVX) and
      sham operation groups. A bone defect was created in the vertebral body 8 weeks
      after the first surgery. In both groups, the vertebral bodies were harvested
      immediately or at 4, 8, or 12 weeks after the second surgery ( n = 7 at each time
      point). Bone volume (BV, mm3), bone volume fraction (BV/TV, %), trabecular
      thickness (Tb.Th, mm), trabecular number (Tb.N, 1/mm), and trabecular separation
      (Tb.Sp, um) were evaluated by micro-computed tomography to assess the new bone
      formation. Histological analysis was also performed. RESULTS: The BV and the
      BV/TV were significantly lower at 4 and 12 weeks in the OVX group compared with
      those in the sham group. The Tb.Th was significantly lower at 8 and 12 weeks in
      the OVX group. Histologically, at 12 weeks, in the OVX group, the bone had a
      thinner, layered structure on the surface of the defect, and the trabecular
      structure was less dense. CONCLUSION: This study demonstrated that bone mass
      formation was suppressed and the quality of repaired bone was poor in the healing
      process of vertebral body defect under osteoporotic conditions. These findings
      could be the key to understand the pathology of osteoporotic vertebral fracture
      and to develop its therapies.

PMID- 29661113
TI  - Histology, vascularity and innervation of the glenoid labrum.
AB  - BACKGROUND: Although the glenoid labrum has an important role in shoulder
      stability, little is known about its composition, vascularity and innervation.
      The aims of this study were therefore to evaluate the histology, vascularity and
      innervation of the glenoid labrum. MATERIALS AND METHODS: Ten glenoid labrum
      specimens (three male, two female: mean age 81.2 years, range 76-90 years) were
      detached at the glenoid neck. Following decalcification, sections were cut
      through the whole thickness of each specimen perpendicular to the glenoid labrum
      at 12 radii corresponding to a clock face superimposed on the glenoid fossa. Then
      they were stained using haematoxylin and eosin, a silver nitrate protocol or
      subjected to immunohistochemistry using anti-protein gene protein 9.5 to
      demonstrate neuronal processes. RESULTS: The labrum was fibrocartilaginous, being
      more fibrous in its free margin. There was a variable distribution of blood
      vessels, being more vascular in its periphery, with many originating from the
      fibrous capsule and piercing the glenoid labrum. Immunohistochemistry revealed
      positive staining of nerve fibres within the glenoid labrum. CONCLUSION: The
      glenoid labrum is fibrocartilaginous, being more fibrous in its periphery, and is
      vascularized, with the anterosuperior aspect having a rich blood supply. Free
      sensory nerve fibres were also present; no encapsulated mechanoreceptors were
      observed. The presence of sensory nerve fibres in the glenoid labrum could
      explain why tears induce pain. It is postulated that these sensory fibres could
      play a role in glenohumeral joint proprioception.

PMID- 29661114
TI  - Pasireotide treatment does not modify hyperglycemic and corticosterone acute
      restraint stress responses in rats.
AB  - Pasireotide is a new-generation somatostatin analog that acts through binding to
      multiple somatostatin receptor subtypes. Studies have shown that pasireotide
      induces hyperglycemia, reduces glucocorticoid secretion, alters
      neurotransmission, and potentially affects stress responses typically manifested
      as hyperglycemia and increased corticosterone secretion. This study specifically
      aimed to evaluate whether pasireotide treatment modifies glucose and
      costicosterone secretion in response to acute restraint stress. Male Holtzman
      rats of 150-200 g were treated with pasireotide (10 ug/kg/day) twice-daily for
      two weeks or vehicle for the same period. Blood samples were collected at
      baseline and after 5, 10, 30, and 60 min of restraint stress. The three
      experimental groups comprised of vehicle + restraint (VEHR), pasireotide +
      restraint (PASR), and pasireotide + saline (PASNR). Following pasireotide
      treatment, no significant differences in baseline glucose and corticosterone
      levels were observed among the three groups. During restraint, hyperglycemia was
      observed at 10 min (p < .01 for both comparisons), peaked at 30 min (p < .01 for
      both comparisons) and showed higher 60 min areas under glucose curves in the VEHR
      and PASR stressed groups when compared to the non-stressed PASNR group (p < .05
      for both comparisons). Restraint also increased corticosterone secretion in the
      VEHR and PASR stressed groups at 5 min (p < .01 for both comparisons), and peaked
      at 30 min (p < .01 for both comparisons) with corresponding higher 60 min areas
      under corticosterone curves when compared to the non-stressed PASNR group (p <
      .01 for both comparisons). In conclusion, pasireotide treatment does not modify
      hyperglycemic- and corticosterone-restraint stress responses, thus preserving
      acute stress regulation.

PMID- 29661115
TI  - Synthesis and evaluation of water soluble pH sensitive poly (vinyl alcohol)
      doxorubicin conjugates.
AB  - The accuracy of spatiotemporal control cargo delivery and release are primordial
      to enhance the therapeutic efficiency and decrease the undesirable effects, in
      this context a novel prodrug were developed based on biocompatible polyvinyl
      alcohol (PVA) substrate. PVA was conjugated to doxorubicin (PVA-DOX) via an acid
      labile hydrazone linkage. PVA was first functionalized with acidic groups, then
      reacted with hydrazine hydrate to form an amide bond. The amine group of PVA
      hydrazide was linked to carbonyl group (C = O) of DOX to form a pH sensitive
      hydrazone bond. The molecular structure of the PVA-DOX was confirmed by FTIR,
      XPS, and 1H-NMR analysis methods. The degree of grafting were evaluated by TGA
      and confirmed by XPS, which reveals the successful bond attachment of DOX to PVA.
      Our findings confirm pH dependent DOX release from PVA-DOX prodrug with faster
      release rate in acidic environment (pH 5.0, pH 6.0) and slower release rate in
      neutral pH environment (pH 7.4). Compared to the primary DOX, our synthesized PVA
      DOX conjugates could exhibit a promising therapeutic effect, high
      biocompatibility and zero premature release. The results prove the successful
      synthesis of PVA-DOX conjugates with high efficiency.

PMID- 29661116
TI  - CRISPR/Cas9-Targeted Deletion of Polyglutamine in Spinocerebellar Ataxia Type 3
      Derived Induced Pluripotent Stem Cells.
AB  - Spinocerebellar ataxia type 3 (SCA3) is caused by an abnormal expansion of the
      cytosine-adenine-guanine (CAG) triplet in ATXN3, which translates into a
      polyglutamine (polyQ) tract within ataxin-3 (ATXN3) protein. Although the
      pathogenic mechanisms remain unclear, it is well established that expression of
      mutant forms of ATXN3 carrying an expanded polyQ domain are involved in SCA3
      pathogenesis, and several strategies to suppress mutant ATXN3 have shown
      promising potential for SCA3 treatment. In this study, we described successful
      clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-mediated
      deletion of the expanded polyQ-encoding region of ATXN3 in induced pluripotent
      stem cells (iPSCs) derived from a SCA3 patient, and these patient-specific iPSCs
      retained pluripotency and neural differentiation following expanded polyQ
      deletion. Furthermore, the ubiquitin-binding capacity of ATXN3 was retained in
      the neural cells differentiated from the corrected iPSCs. For the first time,
      this work provides preliminary data for gene editing by CRISPR/Cas9 in SCA3, and
      demonstrates the feasibility of using a single-guide RNA pair to delete the
      expanded polyQ-encoding region of ATXN3, suggesting the potential efficacy of
      this method for future therapeutic application.

PMID- 29661117
TI  - Sexual Victimization and Mental Illness Prevalence Rates Among Incarcerated
      Women: A Literature Review.
AB  - Incarcerated women evidence high rates of both interpersonal trauma and mental
      illness. In particular, the rates of sexual violence victimization are so high
      that some researchers have suggested that sexual abuse may be a pathway to prison
      for women, likely through the development of mental illness, including substance
      abuse. This review article summarizes the literature on sexual victimization ( n
      = 32 articles; 28 independent studies) and mental illness ( n = 11 articles; 8
      independent studies) prevalence among samples of incarcerated women ( Ns >= 100)
      in context of methodological choices within included articles. Best estimates for
      sexual victimization from studies using established survey methods were as
      follows: 50-66% for child sexual abuse, 28-68% for adult sexual abuse, and 56-82%
      for lifetime sexual assault. Although data directly comparing prevalence of
      sexual victimization among incarcerated women to prevalence for other groups are
      limited, the existing data indicate that incarcerated women have significantly
      greater exposure than incarcerated men and community samples of women. Moreover,
      compared to findings from the National Comorbidity Survey-Replication,
      incarcerated women evidence greater prevalence of most lifetime and current
      mental illnesses, especially depressive disorders, post-traumatic stress
      disorder, and substance use disorders. Surprisingly, only two independent studies
      have investigated the overlap between sexual victimization and mental illness in
      samples of incarcerated women. Both studies found disproportionally high rates of
      mental illness among victims of sexual violence. Suggestions and implications for
      research, policy, and practice are discussed.

PMID- 29661119
TI  - Combined Fatal Systemic Chlamydia sp. and Aeromonas sobria Infection in Juvenile
      Siamese Crocodiles ( Crocodylus siamensis).
AB  - Chlamydial infections in crocodiles have been described in several countries and
      in several different species. These are typically associated with severe
      pharyngitis and conjunctivitis, with death occurring secondary to compromise of
      the upper respiratory tract due to obstruction of the trachea. A population of
      ranched Siamese crocodiles in central Thailand experienced an epizootic of sudden
      death in juvenile animals. The affected animals had fulminant systemic disease
      primarily involving the liver and spleen but also affecting the kidneys, heart,
      and the whole of the respiratory tract. Chlamydia sp. were noted in liver and
      spleen during histopathological examination and confirmed with transmission
      electron microscopy and polymerase chain reaction (PCR). The sequence of the PCR
      product suggested a novel Chlamydia sp. of Siamese crocodiles. Crocodile farming
      represents an important economy in several parts of the world. Epizootics, such
      as the one described in this manuscript in association with Chlamydia sp., can
      have devastating impact on the industry and represent a potential zoonosis of
      significant public health concern. This is the first report of Chlamydia sp. and
      Aeromonas sobria causing systemic disease in crocodiles as well as the first
      histopathological and ultrastructural description of Chlamydia infection in
      Siamese crocodiles.

PMID- 29661120
TI  - Uterine Tumors Resembling Ovarian Sex Cord Tumors in Four Baboons ( Papio spp.).
AB  - Uterine tumors resembling ovarian sex cord tumors (UTROSCTs) are rare uterine
      neoplasms that exhibit prominent sex cord-like differentiation. The authors
      describe 4 cases of UTROSCTs that were identified as incidental lesions in female
      baboons. All baboons were in good body condition. One animal had a 2-mm-diameter
      yellow-tan mass in the uterine body along the attachment of the left broad
      ligament; the other 3 did not have any gross lesions in the uterus.
      Histologically, the myometrium contained multifocal well-demarcated neoplasms
      composed of cuboidal to columnar cells arranged in variable arrangements of
      sheets, nests, cords, trabecular, and retiform patterns that occasionally formed
      Call-Exner-like bodies. In all cases, the neoplastic cells were diffusely
      positive for WT-1 and negative for calretinin, CD99, and desmin. One case was
      positive for inhibin and CD10. To the best of the authors' knowledge, this is the
      first report of UTROSCTs in nonhuman primates and in the veterinary literature.

PMID- 29661121
TI  - Urothelial Carcinomas of the Urinary Bladder With Plasmacytoid or Rhabdoid
      Features and Tendency of Epithelial-Mesenchymal Transition in 3 Dogs.
AB  - Plasmacytoid and rhabdoid variants of urothelial carcinomas (UCs) of the urinary
      bladder have been described in humans with plasma cell-like or rhabdoid cellular
      appearance and aggressive clinical outcome. Canine UC of the bladder is generally
      classified as papillary/nonpapillary and infiltrating/noninfiltrating with
      limited information regarding other histological patterns. We report 3 cases of
      UC of the urinary bladder showing a unique discohesive cellular morphology with
      malignant behavior resembling the human plasmacytoid and rhabdoid variants of UC,
      which may raise some difficulties in diagnosis. Epithelial-mesenchymal transition
      and reduced E-cadherin expression were revealed by immunohistochemistry in 2
      cases, possibly explaining the discohesive and invasive behavior of the tumor
      cells. The findings broaden the morphological spectrum as well as the distinct
      clinical features of canine UC of the urinary bladder.

PMID- 29661122
TI  - Lymphocytic Mural Folliculitis Resembling Epitheliotropic Lymphoma in Tigers (
      Panthera tigris).
AB  - A striking form of lymphocytic mural folliculitis is described in 6 tigers (
      Panthera tigris). Clinically, all tigers exhibited regionally extensive chronic,
      variably waxing and waning alopecia with minimal scaling and crusting most
      pronounced over the head, neck, and shoulders. More severely affected tigers
      exhibited marked hyperpigmentation and lichenification. Pruritus was not a
      feature. Tigers generally lacked signs of systemic illness and clinical pathology
      findings were unremarkable. Histologic examination of skin biopsies revealed
      infiltrative lymphocytic mural folliculitis extending the length of the hair
      follicle. Mild epidermal lymphocytic infiltrates were frequent. The surrounding
      dermis was histologically unremarkable in 4 of 6 tigers or associated with mild
      perifollicular and periadnexal mixed inflammation in 2 of 6 tigers. The cause of
      the mural folliculitis was not identified, and tigers responded poorly to
      immunomodulatory therapy. Lymphocytic mural folliculitis might be a nonspecific
      hypersensitivity reaction pattern in tigers, and care should be taken to
      differentiate this reaction pattern from epitheliotropic T-cell lymphoma.

PMID- 29661123
TI  - Pathological and Microbiological Study of Mortality in a Captive Breeding Colony
      of the Endangered Lord Howe Island Stick Insect ( Dryococelus australis).
AB  - The authors describe pathological and microbiological features of mortalities in
      a captive breeding colony of Lord Howe Island stick insects ( Dryococelus
      australis) over a period of 18 months. There were 2 peaks of mortality in this
      period. In the first, insects presented dead with minimal premonitory signs of
      illness. In the second, affected insects were ataxic with contracted limbs and
      inability to climb or right themselves. Gross lesions were uncommon but included
      pigmented plaques on the gut and cloacal prolapse. Histological lesions in both
      outbreaks indicated a cellular innate immune response including nodulation
      characterized by Gram-negative bacterial bacilli entrapped within nodules of
      pigmented hemocytes, and melanization characterized by melanin within hemocyte
      nodules and around bacteria. Hemolymph culture findings varied and often yielded
      a mixed growth. Pure growth of Serratia marcescens was cultured in 44% of animals
      in Outbreak 1, while pure growth of Pseudomonas aeruginosa was cultured in 30% of
      animals in Outbreak 2. Cases with S. marcescens-positive culture often showed
      inflammation at the foregut-midgut junction. The frequency of mixed bacterial
      culture results did not allow firm conclusions about causality to be made, and
      may indicate primary bacterial infection or increased susceptibility to hemolymph
      colonization with an opportunistic pathogen. These findings highlight the utility
      of histopathology combined with ancillary testing when investigating mortality in
      captive insect colonies.

PMID- 29661124
TI  - Newcastle Disease Virus Infection in Quail.
AB  - Newcastle disease (ND), caused by virulent strains of Newcastle disease virus
      (NDV), is a devastating disease of poultry worldwide. The pathogenesis of ND in
      quail is poorly documented. To characterize the ability of virulent NDV strains
      to replicate and cause disease in quail, groups of 14 two-week-old Japanese quail
      ( Coturnix japonica) were experimentally inoculated with 108 EID50 (embryo
      infectious dose 50%) units of 1 of 4 virulent NDV strains: 2 isolated from quail
      ( N2, N23) and 2 from chickens ( Israel, Pakistan). At day 2 postinfection,
      noninfected quail (contact group) were added to each infection group to assess
      the efficacy of virus transmission. Tested NDV strains showed moderate
      pathogenicity, with highest mortality being 28% for the N2 strain and below 10%
      for the others. Two N2-inoculated birds showed neurological signs, such as head
      tremor and ataxia. Microscopic lesions were present in N2-, Israel-, and Pakistan
      inoculated birds and consisted of nonsuppurative encephalitis. Contact birds
      showed no clinical signs or lesions. In both inoculated and contact birds, virus
      replication was moderate to minimal, respectively, as observed by
      immunohistochemistry in tissues and virus isolation from oropharyngeal and
      cloacal swabs. Strains originally isolated from quail resulted in higher numbers
      of birds shedding in the inoculation group; however, transmission appeared
      slightly more efficient with chicken-derived isolates. This study shows that
      virulent NDV strains have limited replicative potential and mild to moderate
      disease-inducing ability in Japanese quail.

PMID- 29661126
TI  - GNAO1 Mutation-Induced Pediatric Dystonic Storm Rescue With Pallidal Deep Brain
      Stimulation.
AB  - Dystonic storm or status dystonicus is a life-threatening hyperkinetic movement
      disorder with biochemical alterations due to the excessive muscle contractions.
      The medical management can require pediatric intensive care unit admission and a
      combination of medications while the underlying trigger is managed. Severe cases
      may require general anesthesia and paralytic agents with intubation and may
      relapse when these drugs are weaned. Deep brain stimulation of the globus
      pallidum has been reported to terminate dystonic storm in several pediatric
      cases. We present a 10-year-old boy with a de novo GNAO1 mutation-induced
      dystonic storm who required a 2-month pediatric intensive care unit admission and
      remained refractory to all medical treatments. Deep brain stimulation was
      performed under general anesthetic without complication. His dyskinetic movements
      stopped with initiation of stimulation. He was discharged from the pediatric
      intensive care unit after 4 days. We present prospectively evaluated changes in
      dystonia symptoms and quality of life for a patient with GNAO1 mutation treated
      with deep brain stimulation.

PMID- 29661127
TI  - Schistosomiasis mimicking ovarian neoplasm.

PMID- 29661129
TI  - SPIDR: small-molecule peptide-influenced drug repurposing.
AB  - BACKGROUND: Conventional de novo drug design is costly and time consuming, making
      it accessible to only the best resourced research organizations. An emergent
      approach to new drug development is drug repurposing, in which compounds that
      have already gone through some level of clinical testing are examined for
      efficacy against diseases divergent than their original application. Repurposing
      of existing drugs circumvents the time and considerable cost of early stages of
      drug development, and can be accelerated by using software to screen existing
      chemical databases to identify suitable drug candidates. RESULTS: Small-molecule
      Peptide-Influenced Drug Repurposing (SPIDR) was developed to identify small
      molecule drugs that target a specific receptor by exploring the conformational
      binding space of peptide ligands. SPIDR was tested using the potent and selective
      16-amino acid peptide alpha-conotoxin MII ligand and the alpha3beta2-nicotinic
      acetylcholine receptor (nAChR) isoform. SPIDR incorporates a genetic algorithm
      based, heuristic search procedure, which was used to explore the ligand binding
      domain of the alpha3beta2-nAChR isoform using a library consisting of 640,000
      alpha-conotoxin MII peptide analogs. The peptides that exhibited the highest
      affinity for alpha3beta2-nAChR were used as models for a small-molecule structure
      similarity search of the PubChem Compound database. SPIDR incorporates the
      SimSearcher utility, which generates shape distribution signatures of molecules
      and employs multi-level K-means clustering to insure fast database queries. SPIDR
      identified non-peptide drugs with estimated binding affinities nearly double that
      of the native alpha-conotoxin MII peptide. CONCLUSIONS: SPIDR has been
      generalized and integrated into DockoMatic v 2.1. This software contains an
      intuitive graphical interface for peptide mutant screening workflow and
      facilitates mapping, clustering, and searching of local molecular databases,
      making DockoMatic a valuable tool for researchers in drug design and repurposing.

PMID- 29661130
TI  - A survey of functional genomic variation in domesticated chickens.
AB  - BACKGROUND: Deleterious genetic variation can increase in frequency as a result
      of mutations, genetic drift, and genetic hitchhiking. Although individual effects
      are often small, the cumulative effect of deleterious genetic variation can
      impact population fitness substantially. In this study, we examined the genome of
      commercial purebred chicken lines for deleterious and functional variations,
      combining genotype and whole-genome sequence data. RESULTS: We analysed over
      22,000 animals that were genotyped on a 60 K SNP chip from four purebred lines
      (two white egg and two brown egg layer lines) and two crossbred lines. We
      identified 79 haplotypes that showed a significant deficit in homozygous
      carriers. This deficit was assumed to stem from haplotypes that potentially
      harbour lethal recessive variations. To identify potentially deleterious
      mutations, a catalogue of over 10 million variants was derived from 250 whole
      genome sequenced animals from three purebred white-egg layer lines. Out of 4219
      putative deleterious variants, 152 mutations were identified that likely induce
      embryonic lethality in the homozygous state. Inferred deleterious variation
      showed evidence of purifying selection and deleterious alleles were generally
      overrepresented in regions of low recombination. Finally, we found evidence that
      mutations, which were inferred to be evolutionally intolerant, likely have
      positive effects in commercial chicken populations. CONCLUSIONS: We present a
      comprehensive genomic perspective on deleterious and functional genetic variation
      in egg layer breeding lines, which are under intensive selection and
      characterized by a small effective population size. We show that deleterious
      variation is subject to purifying selection and that there is a positive
      relationship between recombination rate and purging efficiency. In addition,
      multiple putative functional coding variants were discovered in selective sweep
      regions, which are likely under positive selection. Together, this study provides
      a unique molecular perspective on functional and deleterious variation in
      commercial egg-laying chickens, which can enhance current genomic breeding
      practices to lower the frequency of undesirable variants in the population.

PMID- 29661132
TI  - Transcriptional development of phospholipid and lipoprotein metabolism in
      different intestinal regions of Atlantic salmon (Salmo salar) fry.
AB  - BACKGROUND: It has been suggested that the high phospholipid (PL) requirement in
      Atlantic salmon (Salmo salar) fry is due to insufficient intestinal de-novo
      synthesis causing low lipoprotein (LP) production and reduced transport capacity
      of dietary lipids. However, in-depth ontogenetic analysis of intestinal PL and LP
      synthesis with the development of salmon has yet to be performed. Therefore, in
      this paper we used RNA-Seq technology to investigate the expression of genes
      involved in PL synthesis and LP formation throughout early developmental stages
      and associate insufficient expression of synthesis pathways in salmon fry with
      its higher dietary PL requirement. There was a special focus on the understanding
      homologous genes, especially those from salmonid-specific fourth vertebrate whole
      genome duplication (Ss4R), and their contribution to salmonid specific features
      of regulation of PL metabolic pathways. Salmon fry were sampled at 0.16 g (1 day
      before first-feeding), 2.5 and 10 g stages of development and transcriptomic
      analysis was applied separately on stomach, pyloric caeca and hindgut of the
      fish. RESULTS: In general, we found up-regulated pathways involved in synthesis
      of phosphatidylcholine (PtdCho), phosphatidylethanolamine (PtdEtn), and LP in
      pyloric caeca of salmon between 0.16 and 10 g. Thirteen differentially expressed
      genes (q < 0.05) in these pathways were highly up-regulated in 2.5 g salmon
      compared to 0.16 g, while only five more differentially expressed (q < 0.05)
      genes were found when the fish grew up to 10 g. Different homologous genes were
      found dominating in stomach, pyloric caeca and hindgut. However, the expression
      of dominating genes in pathways of PL and LP synthesis were much higher in
      pyloric caeca than stomach and hindgut. Salmon-specific homologous genes (Ss4R)
      had similar expression during development, while other homologs had more diverged
      expression. CONCLUSIONS: The up-regulation of the de-novo PtdCho and PtdEtn
      pathways confirm that salmon have decreasing requirement for dietary PL as the
      fish develops. The similar expressions between Ss4R homologous genes suggest that
      the functional divergence of these genes was incomplete compared to homologs
      derived from other genome duplication. The results of the present study have
      provided new information on the molecular mechanisms of phospholipid synthesis
      and lipoprotein formation in fish.

PMID- 29661131
TI  - Transcriptome profiling of Brassica napus stem sections in relation to
      differences in lignin content.
AB  - BACKGROUND: Brassica crops are cultivated widely for human consumption and animal
      feed purposes, and oilseed rape/canola (Brassica napus and rapa) is the second
      most important oilseed worldwide. Because of its natural diversity and genetic
      complexity, genomics studies on oilseed rape will be a useful resource base to
      modify the quantity and quality of biomass in various crops, and therefore,
      should have a positive impact on lignocellulosic biofuel production. The
      objective of this study was to perform microarray analysis on two variable lignin
      containing oilseed rape cultivars to target novel genes and transcription factors
      of importance in Brassica lignin regulation for applied research. RESULTS: To
      gain insight into the molecular networks controlling cell wall biosynthetic and
      regulatory events, we conducted lignin and microarray analysis of top and basal
      stem sections of brown seeded Brassica napus DH12075 and yellow seeded YN01-429
      cultivars. A total of 9500 genes were differentially expressed 2-fold or higher
      in the stem between the cultivars, with a higher number of expressed genes in the
      basal section. Of the upregulated genes, many were transcription factors and a
      considerable number of these were associated with secondary wall synthesis and
      lignification in B. napus and other plant species. The three largest groups of
      transcription factors with differential expression were C2H2 and C3HC4 zinc
      fingers and bHLH. A significant number of genes related to lignin and
      carbohydrate metabolism also showed differential expression patterns between the
      stem sections of the two cultivars. Within the same cultivar, the number of
      upregulated genes was higher in the top section relative to the basal one.
      CONCLUSION: In this study, we identified and established expression patterns of
      many new genes likely involved in cell wall biosynthesis and regulation. Some
      genes with known roles in other biochemical pathways were also identified to have
      a potential role in cell wall biosynthesis. This stem transcriptome profiling
      will allow for selecting novel regulatory and structural genes for functional
      characterization, a strategy which may provide tools for modifying cell wall
      composition to facilitate fermentation for biofuel production.

PMID- 29661133
TI  - The impact of genome editing on the introduction of monogenic traits in
      livestock.
AB  - BACKGROUND: Genome editing technologies provide new tools for genetic improvement
      and have the potential to become the next game changer in animal and plant
      breeding. The aim of this study was to investigate how genome editing in
      combination with genomic selection can accelerate the introduction of a monogenic
      trait in a livestock population as compared to genomic selection alone. METHODS:
      A breeding population was simulated under genomic selection for a polygenic
      trait. After reaching Bulmer equilibrium, the selection objective was to increase
      the allele frequency of a monogenic trait, with or without genome editing, in
      addition to improving the polygenic trait. Scenarios were compared for time to
      fixation of the desired allele, selection response for the polygenic trait, and
      level of inbreeding. The costs, in terms of number of editing procedures, were
      compared to the benefits of having more animals with the desired phenotype of the
      monogenic trait. Effects of reduced editing efficiency were investigated.
      RESULTS: In a population of 20,000 selection candidates per generation, the total
      number of edited zygotes needed to reach fixation of the desired allele was
      22,118, 7072, or 3912 with, no, moderate, or high selection emphasis on the
      monogenic trait, respectively. Genome editing resulted in up to four-fold faster
      fixation of the desired allele when efficiency was 100%, while the loss in long
      term selection response for the polygenic trait was up to seven-fold less
      compared to genomic selection alone. With moderate selection emphasis on the
      monogenic trait, introduction of genome editing led to a four-fold reduction in
      the total number of animals showing the undesired phenotype before fixation.
      However, with a currently realistic editing efficiency of 4%, the number of
      required editing procedures increased by 72% and loss in selection response
      increased eight-fold compared to 100% efficiency. With low efficiency, loss in
      selection response was 29% more compared to genomic selection alone. CONCLUSIONS:
      Genome editing strongly decreased the time to fixation for a desired allele
      compared to genomic selection alone. Reduced editing efficiency had a major
      impact on the number of editing procedures and on the loss in selection response.
      In addition to ethical and welfare considerations of genome editing, a careful
      assessment of its technical costs and benefits is required.

PMID- 29661135
TI  - The relative burden of community-acquired pneumonia hospitalizations in older
      adults: a retrospective observational study in the United States.
AB  - BACKGROUND: The risk of community-acquired pneumonia (CAP) increases with age and
      significantly impacts morbidity and mortality in the elderly population. The
      burden of illness and cost of preventing CAP has not been compared to other
      serious diseases. METHODS: This retrospective analysis used claims data from 2014
      to 2015 and compared hospitalizations for CAP, myocardial infarction (MI),
      stroke, and osteoporotic fractures (OF) in adults aged >=65 years enrolled in a
      Medicare Advantage insurance plan. Individuals who had not already been
      hospitalized for one of these conditions and did not have evidence of long-term
      care were included in the study. Hospitalizations for each condition were
      described by length of stay, readmissions, mortality, and total costs. Preventive
      measures included vaccinations for CAP and medications for MI, stroke, and OF.
      RESULTS: A total of 1,949,352 individuals were included in the cohort. In 2015,
      the rate of CAP-related hospitalizations was the highest at 846.7 per 100,000
      person-years compared to 405 for MI, 278.9 for stroke, and 343.9 for OF.
      Vaccination costs for CAP were $40.2 million including $14.1 million for
      pneumococcal and $26.1 million for influenza vaccines. The cost of preventive
      medications for MI and stroke reached over $661 million and OF totaled $169
      million. CONCLUSIONS: Although CAP has a higher burden of hospitalization and
      total costs than MI, stroke, and OF in the elderly population, prevention efforts
      were disproportionately smaller for CAP. Prioritization of CAP prevention is
      needed to substantially reduce the burden of CAP.

PMID- 29661134
TI  - Transcriptome analysis of granulosa cells after conventional vs long FSH-induced
      superstimulation in cattle.
AB  - BACKGROUND: Prolongation of superstimulatory treatment appears to be associated
      with a greater superovulatory response and with greater oocyte maturation in
      cattle. A genome-wide bovine oligo-microarray was used to compare the gene
      expression of granulosa cells collected from ovarian follicles after differing
      durations of the growing phase induced by exogenous FSH treatment. Cows were
      given a conventional (4-day) or long (7-day) superstimulatory treatment (25 mg
      FSH im at 12-h intervals; n = 6 per group), followed by prostaglandin treatment
      with last FSH and LH treatment 24 h later. Granulosa cells were harvested 24 h
      after LH treatment. RESULTS: The expression of 416 genes was down-regulated and
      615 genes was up-regulated in the long FSH group compared to the conventional FSH
      group. Quantification by RT-PCR of 7 genes (NTS, PTGS2, PTX3, RGS2, INHBA, CCND2
      and LRP8) supported the microarrays data. Multigene bioinformatic analysis
      indicates that markers of fertility and follicle maturity were up-regulated in
      the long FSH group. CONCLUSION: Using the large gene expression dataset generated
      by the genomic analysis and our previous associated with the growth phase and
      gene expression changes post LH, we can conclude that a prolonged FSH-induced
      growing phase is associated with transcriptomic characteristics of greater
      follicular maturity and may therefore be more appropriate for optimizing the
      superovulatory response and developmental competence of oocytes in cattle.

PMID- 29661136
TI  - Effects of a community health promotion program on social factors in a vulnerable
      older adult population residing in social housing.
AB  - BACKGROUND: Supporting older adults' health and wellbeing in the community is an
      important policy goal that can be supported by health promotion. Despite
      widespread acceptance of the biopsychosocial model of health and its relation to
      health, many health promotion programs fail to realize this model in program
      design. Further, there is limited evidence to support program design targeting
      social determinants of health such as social isolation or connectedness. To fill
      this gap, we aimed to understand older adult's experiences participating in
      cardiovascular health promotion program in a subsidized residential building to
      capture unintended 'spin-off' psychosocial effects. METHODS: This study took a
      constructivist, ethnographic approach utilizing participant observation and semi
      structured interviews with participants of the program to understand
      participant's lived experiences of a health promotion program. In total, we
      conducted eighty hours of field work and fifteen semi-structured interviews with
      participants of the program. Thematic analysis was used to analyze the data.
      RESULTS: Four themes emerged. First, the health promotion program filled a
      perceived gap caused by a constrained and impersonal health care system.
      Secondly, the program connected older adults with resources and provided regular
      and secure access to health information and support. Third, for some residents,
      the program facilitated social relationships between older adults, leaving
      participants feeling more socially connected to other residents. Lastly, a
      paradox of loneliness emerged where older adults talked openly about feelings of
      loneliness, however not in relation to themselves, but rather regarding their
      peers. CONCLUSIONS: Psychosocial aspects of health, such as loneliness, social
      connectedness, and social support may be of equal value as the physical health
      benefits to the older adults who participate in health promotion programs.
      Incorporating these elements into programming is a complex goal, and the
      complexity of targeting social determinants of health such as social loneliness
      or connectedness should not be under-estimated. Given the benefits of targeting
      social determinants of health, future research should be considered that measure
      both the objective and subjective aspects of social isolation, loneliness and
      connectedness in health promotion programming.

PMID- 29661137
TI  - 1000 human genomes carry widespread signatures of GC biased gene conversion.
AB  - BACKGROUND: GC-Biased Gene Conversion (gBGC) is one of the important theories put
      forward to explain profound long-range non-randomness in nucleotide compositions
      along mammalian chromosomes. Nucleotide changes due to gBGC are hard to
      distinguish from regular mutations. Here, we present an algorithm for analysis of
      millions of known SNPs that detects a subset of so-called "SNP flip-over" events
      representing recent gBGC nucleotide changes, which occurred in previous
      generations via non-crossover meiotic recombination. RESULTS: This algorithm has
      been applied in a large-scale analysis of 1092 sequenced human genomes.
      Altogether, 56,328 regions on all autosomes have been examined, which revealed
      223,955 putative gBGC cases leading to SNP flip-overs. We detected a strong bias
      (11.7% +/- 0.2% excess) in AT- > GC over GC- > AT base pair changes within the
      entire set of putative gBGC cases. CONCLUSIONS: On average, a human gamete
      acquires 7 SNP flip-over events, in which one allele is replaced by its
      complementary allele during the process of meiotic non-crossover recombination.
      In each meiosis event, on average, gBGC results in replacement of 7 AT base pairs
      by GC base pairs, while only 6 GC pairs are replaced by AT pairs. Therefore,
      every human gamete is enriched by one GC pair. Happening over millions of years
      of evolution, this bias may be a noticeable force in changing the nucleotide
      composition landscape along chromosomes.

PMID- 29661138
TI  - A Coxiella burnetii phospholipase A homolog pldA is required for optimal growth
      in macrophages and developmental form lipid remodeling.
AB  - BACKGROUND: Many gram-negative bacteria produce an outer membrane phospholipase A
      (PldA) that plays an important role in outer membrane function and is associated
      with virulence. RESULTS: In the current study, we characterized a pldA mutant of
      Coxiella burnetii, an intracellular gram-negative pathogen and the agent of human
      Q fever. The C. burnetti pldA open reading frame directs synthesis of a protein
      with conserved PldA active site residues. A C. burnetii DeltapldA deletion mutant
      had a significant growth defect in THP-1 macrophages, but not axenic medium, that
      was rescued by complementation. Thin layer chromatography was employed to assess
      whether pldA plays a role in remodeling membrane lipids during C. burnetii
      morphological differentiation. Extracted lipids were analyzed from replicating,
      logarithmic phase large cell variants (LCVs), non-replicating, stationary phase
      small cell variants (SCVs), and a mixture of LCVs and SCVs. Similar to
      Escherichia coli, all three forms contained cardiolipin (CL),
      phosphatidylglycerol (PG) and phosphatidylethanolamine (PE). However, PE and PG
      were present in lower quantities in the SCV while three additional lipid species
      were present in higher quantities. Co-migration with standards tentatively
      identified two of the three SCV-enriched lipids as lyso-phosphatidylethanolamine,
      a breakdown product of PE, and free fatty acids, which are generally toxic to
      bacteria. Developmental form lipid modifications required the activity of PldA.
      CONCLUSIONS: Collectively, these results indicate developmentally-regulated lipid
      synthesis by C. burnetii contributes to colonization of macrophages and may
      contribute to the environmental stability and the distinct biological properties
      of the SCV.

PMID- 29661139
TI  - Genome analysis of the freshwater planktonic Vulcanococcus limneticus sp. nov.
      reveals horizontal transfer of nitrogenase operon and alternative pathways of
      nitrogen utilization.
AB  - BACKGROUND: Many cyanobacteria are capable of fixing atmospheric nitrogen,
      playing a crucial role in biogeochemical cycling. Little is known about
      freshwater unicellular cyanobacteria Synechococcus spp. at the genomic level,
      despite being recognised of considerable ecological importance in aquatic
      ecosystems. So far, it has not been shown whether these unicellular
      picocyanobacteria have the potential for nitrogen fixation. Here, we present the
      draft-genome of the new pink-pigmented Synechococcus-like strain Vulcanococcus
      limneticus. sp. nov., isolated from the volcanic Lake Albano (Central Italy).
      RESULTS: The novel species Vulcanococcus limneticus sp. nov. falls inside the sub
      cluster 5.2, close to the estuarine/marine strains in a maximum-likelihood
      phylogenetic tree generated with 259 marker genes with representatives from
      marine, brackish, euryhaline and freshwater habitats. V.limneticus sp. nov.
      possesses a complete nitrogenase and nif operon. In an experimental setup under
      nitrogen limiting and non-limiting conditions, growth was observed in both cases.
      However, the nitrogenase genes (nifHDK) were not transcribed, i.e., V.limneticus
      sp. nov. did not fix nitrogen, but instead degraded the phycobilisomes to produce
      sufficient amounts of ammonia. Moreover, the strain encoded many other pathways
      to incorporate ammonia, nitrate and sulphate, which are energetically less
      expensive for the cell than fixing nitrogen. The association of the nif operon to
      a genomic island, the relatively high amount of mobile genetic elements (52
      transposases) and the lower observed GC content of V.limneticus sp. nov. nif
      operon (60.54%) compared to the average of the strain (68.35%) support the theory
      that this planktonic strain may have obtained, at some point of its evolution,
      the nif operon by horizontal gene transfer (HGT) from a filamentous or
      heterocystous cyanobacterium. CONCLUSIONS: In this study, we describe the novel
      species Vulcanococcus limneticus sp. nov., which possesses a complete nif operon
      for nitrogen fixation. The finding that in our experimental conditions
      V.limneticus sp. nov. did not express the nifHDK genes led us to reconsider the
      actual ecological meaning of these accessory genes located in genomic island that
      have possibly been acquired via HGT.

PMID- 29661140
TI  - The biochemical composition and transcriptome of cotyledons from Brassica napus
      lines expressing the AtGL3 transcription factor and exhibiting reduced flea
      beetle feeding.
AB  - BACKGROUND: Previously, transgenic trichome-bearing (hairy leaf) Brassica napus
      lines expressing either the Arabidopsis thaliana GL3 gene (line AtGL3+) [1] or
      the AtGL3 gene in combination with an RNAi construct to down-regulate TTG1 (line
      K-5-8) [2] were developed. The leaves of these lines exhibited altered insect
      feeding (flea beetle) and oviposition (diamondback moth) behaviour compared to
      the non-transgenic semi-glabrous leaves of B. napus cv. Westar. Interestingly,
      the cotyledons of these lines remained glabrous, but also showed reduced feeding
      by flea beetles. Here we examine the composition and global transcriptome of the
      glabrous cotyledons from these transgenic lines to ascertain the mechanism(s)
      underlying this unexpected phenomenon. RESULTS: Approximately, 7500 genes were up
      regulated in cotyledons of each hairy line, compared with < 30 that were down
      regulated. The up-regulated genes included those involved in cell wall synthesis,
      secondary metabolite production, redox, stress and hormone-related responses that
      have the potential to impact host plant cues required to elicit defense responses
      toward insect pests. In particular, the expression of glucosinolate biosynthetic
      and degradation genes were substantially altered in the glabrous cotyledons of
      the two hairy leaf lines. The transcriptomic data was supported by glucosinolate
      and cell wall composition profiles of the cotyledons. Changes in gene expression
      were much more extreme in the AtGL3+ line compared with the K-5-8 line in terms
      of diversity and intensity. CONCLUSIONS: The study provides a roadmap for the
      isolation and identification of insect resistance compounds and proteins in the
      glabrous cotyledons of these hairy leaf lines. It also confirms the impact of mis
      expression of GL3 and TTG1 on types of metabolism other than those associated
      with trichomes. Finally, the large number of up-regulated genes encoding heat
      shock proteins, PR proteins, protease inhibitors, glucosinolate
      synthesis/breakdown factors, abiotic stress factors, redox proteins,
      transcription factors, and proteins required for auxin metabolism also suggest
      that these cotyledons are now primed for resistance to other forms of biotic and
      abiotic stress.

PMID- 29661141
TI  - Diagnostic utility of monitoring cytomegalovirus-specific immunity by QuantiFERON
      cytomegalovirus assay in kidney transplant recipients.
AB  - BACKGROUND: Despite universal prophylaxis, late cytomegalovirus (CMV) infection
      occurs in a high proportion of kidney transplant recipients. We evaluated whether
      a specific viral T-cell response allows for the better identification of
      recipients who are at high risk of CMV infection after prophylaxis withdrawal.
      METHODS: We conducted a prospective study in 19 pretransplant anti-CMV
      seronegative kidney graft recipients R- (18 from seropositive donors [D+] and one
      from a seronegative donor [D-]) and 67 seropositive recipients R(+) (59 from
      seropositive donors and eight from seronegative donors) who received antiviral
      prophylaxis with valganciclovir. The QuantiFERON-CMV (QF-CMV) assay was performed
      within the first and third months after transplantation. Blood samples were
      monitored for CMV DNAemia using a commercial quantitative nucleic acid
      amplification test (QNAT) that was calibrated to the World Health Organization
      International Standard. RESULTS: Twenty-one of the 86 patients (24%) developed
      CMV viremia after prophylaxis withdrawal within 12 months posttransplantation. In
      the CMV R(+) group, the QF-CMV assay yielded reactive results (QF-CMV[+]) in 51
      of 67 patients (76%) compared with 7 of 19 patients (37%) in the CMV R(-) group
      (p = 0.001). In the CMV R(+) group, infection occurred in seven of 16 recipients
      (44%) who were QF-CMV(-) and eight of 51 recipients (16%) who were QF-CMV(+). In
      the CMV R(-) group, infection evolved in five of 12 recipients (42%) who were QF
      CMV(-) and one of 7 recipients (14%) who were QF-CMV(+). No difference was found
      in the incidence of CMV infection stratified according to the QF-CMV results with
      regard to the recipients' pretransplant CMV IgG serology (p = 0.985).
      Cytomegalovirus infection occurred in 15 of 36 patients (42%) with
      hypogammaglobulinemia (HGG) 90 days posttransplantation compared with two of 34
      patients (6%) without HGG (p = 0.0004). Cytomegalovirus infection occurred in
      seven of 13 patients (54%) with lymphocytopenia compared with 14 of 70 patients
      (20%) without lymphocytopenia (p = 0.015). The multivariate analysis revealed
      that the nonreactive QuantiFERON-CMV assay was an independent risk factor for
      postprophylaxis CMV infection. CONCLUSIONS: In kidney transplant recipients who
      received posttransplantation prophylaxis, negative QF-CMV results better defined
      the risk of CMV infection than initial CMV IgG status after prophylaxis
      withdrawal. Hypogammaglobulinemia and lymphocytopenia were risk factors for CMV
      infection.

PMID- 29661142
TI  - Neutrophils in primary gastric tumors are correlated with neutrophil infiltration
      in tumor-draining lymph nodes and the systemic inflammatory response.
AB  - BACKGROUND: Tumor-Associated Neutrophils (TANs) may be able to induce
      lymphangiogenesis and angiogenesis, although the detailed roles of TANs remain
      unclear. The Neutrophil-Lymphocyte Ratio (NLR) is an inflammation-based
      prognostic factor for gastric cancer. This study aimed to investigate the
      distribution of CD15+neutrophils in the primary tumor and Tumor-Draining Lymph
      Nodes (TDLNs), and to examine the association of TANs with the
      clinicopathological features (including NLR) of patients with gastric cancer.
      RESULTS: Immunohistochemical staining showed that the median number of CD15+TANs
      was 18 and 24 per high-power field (HPF) in primary tumors and TDLNs,
      respectively. Patients were divided into high and low infiltration groups based
      on the median number. A high number of infiltrating CD15+TANs in the primary
      tumors and in the TDLNs were associated with depth of invasion and lymph node
      metastasis. Kaplan-Meier analysis revealed that a poor overall survival was
      associated with high numbers of CD15+TANs, and the multivariate analyses revealed
      that a high number of CD15+TANs in the TDLNs was an independent prognostic
      factor. The numbers of CD15+TANs in the primary tumors and TDLNs showed weak
      positive correlation. The number of CD15+TANs in the primary tumors was
      positively correlated with the preoperative NLR, (P = 0.001, R = 0.327) and
      immunohistochemical staining revealed that C-X-C motif chemokine receptor 2
      (CXCR2) +neutrophils might be the origin of the CD15+TANs. Flow cytometry
      analysis indicated that infiltrating neutrophils increased in the tumor and TDLN
      compared to non-cancerous tissue. Neutrophils treated with cancer supernatant
      upregulated TWIST and IL-6 genes in vitro. CONCLUSION: Our findings suggested
      that local infiltration of CD15+TANs may be correlated with inflammation in TDLNs
      and systemic response to cause metastasis in gastric carcinoma.

PMID- 29661143
TI  - Dietary habits and Helicobacter pylori infection: a cross sectional study at a
      Lebanese hospital.
AB  - BACKGROUND: To examine the association between dietary habits and Helicobacter
      pylori (H. pylori) infection among patients at a tertiary healthcare center in
      Lebanon. METHODS: This cross-sectional study was conducted on 294 patients in
      2016, at a hospital in Northern Lebanon. Participants were interviewed using a
      structured questionnaire to collect information on socio-demographic and
      lifestyle characteristics; dietary habits were ascertained via a short food
      frequency questionnaire (FFQ). H. pylori status (positive vs. negative) was
      determined after upper GI endoscopy where gastric biopsy specimens from the
      antrum, body, and fundus region were collected and then sent for pathology
      analysis. Multivariable logistic regression was conducted to identify the
      association between socio-demographic, lifestyle, dietary and other health
      related variables with H pylori infection. RESULTS: The prevalence of H. pylori
      infection was found to be 52.4% in this sample. Results of the multivariable
      analysis showed that H. pylori infection risk was higher among participants with
      a university education or above (OR = 2.74; CI = 1.17-6.44), those with a history
      of peptic ulcers (OR = 3.80; CI = 1.80-8.01), gastric adenocarcinoma (OR = 3.99;
      CI = 1.35-11.83) and vitamin D level below normal (OR = 29.14; CI = 11.77-72.13).
      In contrast, hyperglycemia was protective against H. pylori (OR = 0.18; CI = 0.03
      0.89). No relationship between dietary habits and H. pylori infection was found
      in the adjusted analysis. CONCLUSIONS: Socio-demographic and clinical variables
      are found to be associated with H. pylori, but not with dietary factors. Further
      studies are needed to investigate the effect of diet on H. pylori risk.

PMID- 29661144
TI  - Pretreatment with nimodipine reduces incidence of POCD by decreasing calcineurin
      mediated hippocampal neuroapoptosis in aged rats.
AB  - BACKGROUND: Calcineurin (CaN) having a high expression in hippocampal neurons is
      closely related to apoptosis. Pretreatment with nimodipine can lower the
      apoptosis rate of hippocampal neuron to reduce the incidence of postoperative
      cognitive dysfunction (POCD). However, the relationship between cerebral
      protective effect of pretreatment with nimodipine and CaN is controversial in the
      literature. The aim of this study is to evaluate the relationship between
      neuroprotective effect of nimodipine and CaN on POCD in aged rats. METHODS:
      Ninety-six 18-month-old male Sprague-Dawley rats were randomly assigned into 4
      groups (n = 24 each): control group (Group C), nimodipine group (Group N),
      surgery group (Group S) and nimodipine + surgery group (Group N + S). In Group N
      and Group N + S, nimodipine 1 mg/kg was intraperitoneally injected, while the
      equal volume of normal saline was given instead in Group S. 30 min later, Group N
      and Group C inhaled pure oxygen for 2 h, and Group S and N + S inhaled 3%
      sevoflurane for 2 h when exploratory laparotomy was performed. Morris water maze
      test was performed on 1 day before operation and 1, 3 and 7 days after operation.
      After the end of Morris water maze test at 1 day before operation and 1 and 7
      days after operation, 8 rats were sacrificed, brains were removed and hippocampal
      tissues were obtained for detection of apoptosis in hippocampal neurons,
      cytoplasmic calcium ([Ca2+]i), and hippocampal CaN and caspase-3 expression.
      RESULTS: Compared with the 1st day before operation, the escape latency,
      apoptosis rate, [Ca2+]i, expression of CaN and caspase-3 increased significantly,
      but the frequency of crossing the original platform decreased dramatically in
      Group S and N + S(P<0.05). In addition, the escape latency, apoptosis rate,
      [Ca2+]i, and expression of CaN and caspase-3 decreased markedly, but the
      frequency of crossing the original platform increased significantly in Group N +
      S as compared with Group S (P<0.05). CONCLUSIONS: Pretreatment with nimodipine
      reduces the incidence of POCD by decreasing CaN mediated hippocampal
      neuroapoptosis in aged rats.

PMID- 29661145
TI  - Therapeutic cancer vaccine: phase I clinical tolerance study of Hu-rhEGF
      rP64k/Mont in patients with newly diagnosed advanced non-small cell lung cancer.
AB  - BACKGROUND: Hu-rhEGF-rP64k/Mont is a biotechnology product for the treatment of
      advanced non-small cell lung cancer (NSCLC). The vaccine induces a neutralizing
      antibody-mediated immune response, against the normal circulating self-protein
      antigen epidermal growth factor (EGF), which prevents its binding to and
      activation of the EGF receptor, inhibiting the transduction of the signals that
      drive cancer cell proliferation, survival and spread. This phase I study aimed to
      evaluate the safety and the immunological response of Hu-rhEGF-rP64k vaccine in
      NSCLC patients. RESULTS: The Hu-rhEGF-rP64k/Mont vaccine showed to be safe and
      well tolerated, with dizziness, injection-site reactions and tremors being the
      most commonly reported adverse event. No severe adverse events or death were
      related to the vaccination. Immune monitoring demonstrated the generation of anti
      EGF antibody titers and as a consequence the patients exhibited a decrease in the
      EGF concentration. In 80% of the vaccinated patients stable disease was achieved.
      CONCLUSION: Hu-rhEGF-rP64k/Mont elicited a valuable immune response, with good
      safety profile assuring further clinical development of the vaccine in this
      population to further confirm the potential benefits on survival. TRIAL
      REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-OID-17014048 , date
      2017/12/20 (retrospectively registered); Chinese Food and Drug Administration,
      CFDA 2009 L02105, date 2009/04/03; China Drug Trial, CTR20131039 .

PMID- 29661146
TI  - Slow darkening of pinto bean seed coat is associated with significant metabolite
      and transcript differences related to proanthocyanidin biosynthesis.
AB  - BACKGROUND: Postharvest seed coat darkening in pinto bean is an undesirable trait
      resulting in a loss in the economic value of the crop. The extent of darkening
      varies between the bean cultivars and their storage conditions. RESULTS:
      Metabolite analysis revealed that the majority of flavonoids including
      proanthocyanidin monomer catechin accumulated at higher level in a regular
      darkening (RD) pinto line CDC Pintium than in a slow darkening (SD) line 1533-15.
      A transcriptome analysis was conducted to compare gene expression between CDC
      Pintium and 1533-15 and identify the gene (s) that may play a role in slow
      darkening processes in 1533-15 pinto. RNAseq against total RNA from RD and SD
      cultivars found several phenylpropanoid genes, metabolite transporter genes and
      genes involved in gene regulation or modification to be differentially expressed
      between CDC Pintium and 1533-15. CONCLUSION: RNAseq analysis and metabolite data
      of seed coat tissue from CDC Pintium and 1533-15 revealed that the whole
      proanthocyanidin biosynthetic pathway was downregulated in 1533-15. Additionally,
      genes that encode for putative transporter proteins were also downregulated in
      1533-15 suggesting both synthesis and accumulation of proanthocyanidin is reduced
      in SD pintos.

PMID- 29661147
TI  - Genotyping of Plasmodiophora brassicae reveals the presence of distinct
      populations.
AB  - BACKGROUND: Plasmodiophora brassicae is a soilborne pathogen of the family
      Brassicaceae and the causal agent of clubroot disease. In Canada, P. brassicae is
      now one of the most important constraints to canola (Brassica napus) production,
      and is managed mainly by the deployment of resistant cultivars. In recent years,
      however, new strains of the pathogen have emerged that are capable of overcoming
      host resistance, posing new challenges for disease management. Despite its
      economic significance, molecular studies of P. brassicae are rare, mainly because
      this microorganism cannot be cultured outside of its host. RESULTS: Restriction
      site-associated DNA sequencing (RADseq) was used to examine the genetic diversity
      within P. brassicae single-spore and field isolates collected from across Canada.
      The isolates included individuals that were either capable or incapable of
      causing disease on clubroot resistant canola cultivars. Over 8750 variants were
      identified through RADseq. Population analysis indicated that most isolates
      belonged to one of two distinct populations, corresponding with the ability of
      isolates to cause disease on resistant cultivars. Within each population, there
      were low levels of genetic diversity. One thousand and fifty of the genetic
      variants that distinguished the two populations were nonsynonymous, altering the
      coding sequences of genes. CONCLUSION: The application of RADseq revealed two
      distinct populations of P. brassicae in Canada, suggesting multiple introductions
      of the pathogen into the country. The genetic variation found here will be
      important for future research and monitoring of the pathogen.

PMID- 29661148
TI  - Identification of missing variants by combining multiple analytic pipelines.
AB  - BACKGROUND: After decades of identifying risk factors using array-based genome
      wide association studies (GWAS), genetic research of complex diseases has shifted
      to sequencing-based rare variants discovery. This requires large sample sizes for
      statistical power and has brought up questions about whether the current variant
      calling practices are adequate for large cohorts. It is well-known that there are
      discrepancies between variants called by different pipelines, and that using a
      single pipeline always misses true variants exclusively identifiable by other
      pipelines. Nonetheless, it is common practice today to call variants by one
      pipeline due to computational cost and assume that false negative calls are a
      small percent of total. RESULTS: We analyzed 10,000 exomes from the Alzheimer's
      Disease Sequencing Project (ADSP) using multiple analytic pipelines consisting of
      different read aligners and variant calling strategies. We compared variants
      identified by using two aligners in 50,100, 200, 500, 1000, and 1952 samples; and
      compared variants identified by adding single-sample genotyping to the default
      multi-sample joint genotyping in 50,100, 500, 2000, 5000 and 10,000 samples. We
      found that using a single pipeline missed increasing numbers of high-quality
      variants correlated with sample sizes. By combining two read aligners and two
      variant calling strategies, we rescued 30% of pass-QC variants at sample size of
      2000, and 56% at 10,000 samples. The rescued variants had higher proportions of
      low frequency (minor allele frequency [MAF] 1-5%) and rare (MAF < 1%) variants,
      which are the very type of variants of interest. In 660 Alzheimer's disease cases
      with earlier onset ages of <=65, 4 out of 13 (31%) previously-published rare
      pathogenic and protective mutations in APP, PSEN1, and PSEN2 genes were
      undetected by the default one-pipeline approach but recovered by the multi
      pipeline approach. CONCLUSIONS: Identification of the complete variant set from
      sequencing data is the prerequisite of genetic association analyses. The current
      analytic practice of calling genetic variants from sequencing data using a single
      bioinformatics pipeline is no longer adequate with the increasingly large
      projects. The number and percentage of quality variants that passed quality
      filters but are missed by the one-pipeline approach rapidly increased with sample
      size.

PMID- 29661149
TI  - Development of the tonsillar microbiome in pigs from newborn through weaning.
AB  - BACKGROUND: Porcine tonsils are lympho-epithelial tissues, colonized by numerous
      bacteria and viruses, that act as a reservoir for both host-specific pathogens
      and zoonotic pathogens with a high potential of transmission to humans. There are
      no existing studies describing the development of the tonsillar microbiome. We
      sequenced 16S rRNA genes from tonsillar samples of pigs to follow the development
      of the microbial communities from birth through weaning. Samples derived from
      sows were also analyzed to determine potential sources for the tonsil microbiome
      in piglets. RESULTS: The composition of the newborn piglet tonsil microbiome
      could be differentiated by litter and had strong similarity to the sow teat skin
      as well as sow vaginal microbiome. The tonsil microbiome in these young piglets
      was mainly dominated by members of the Pasteurellaceae, Moraxellaceae, and
      Streptococcaceae families, while there were some transient members of the
      microbiome that were abundant at specific times, such as Staphylococcaceae in
      newborns and Fusobacteriaceae and Leptotrichiaceae in weeks 2 and 3. The
      microbiome initially differed between litters but over the following 3 weeks the
      communities of different litters converged in composition and then diverged in
      week 4 due to a combination of changes and stresses associated with weaning,
      including a shift from milk to a solid diet, in-feed Carbadox(r) and room change.
      CONCLUSIONS: A significant portion of the tonsil microbiome was acquired either
      at birth from the sow vaginal tract or within a few hours post-birth from the sow
      teat skin. Our data demonstrate a temporal succession in the development of the
      pig tonsillar microbiome through the first weeks of life, with a convergence in
      the composition of the microbiome in all piglets by 3 weeks of age. The
      combination of management practices associated with weaning coincided with
      dramatic shifts in the tonsillar microbiome.

PMID- 29661150
TI  - A moderate 500-m treadmill walk for estimating peak oxygen uptake in men with
      NYHA class I-II heart failure and reduced left ventricular ejection fraction.
AB  - BACKGROUND: Maximal cardiopulmonary exercise testing (CPX) is the gold-standard
      for cardiorespiratory fitness assessment in chronic heart failure (CHF) patients.
      However, high costs, required medical supervision, and safety concerns make
      maximal exercise testing impractical for evaluating mobility-impaired adults.
      Thus, several submaximal walking protocols have been developed and currently used
      to estimate peak oxygen consumption (VO2peak) in CHF patients. However, these
      tests have to be performed at close to maximum exercise intensity. The aim of
      this study was to examine the validity of a 500-m treadmill-walking test carried
      out at moderate intensity for estimating VO2peak in community-dwelling adult and
      elderly patients with CHF and reduced left ventricular ejection fraction (HFrEF).
      METHODS: Forty-three clinically stable men with HFrEF (age 67.7 +/- 9.2 years,
      and left ventricular ejection fraction, LVEF 38% +/- 6%) underwent exercise
      testing during an outpatient cardiac rehabilitation/secondary prevention program.
      Each patients completed a CPX, and a moderate and self-paced (11-13/20 on the
      Borg scale) 500-m treadmill-walking test. Age, weight, height, walk time, and
      heart rate during the 500-m test were entered into prediction equations
      previously validated for VO2peak estimation from a 1000-m walking test in
      patients with cardiovascular disease and preserved LVEF. RESULTS: Directly
      measured and estimated VO2peak values were not different (21.6 +/- 4.9 vs 21.7 +/
      4.6 mL/kg/min). The comparison between measured and estimated VO2peak values
      yielded a correlation of R = 0.97 (SEE = 0.7 mL/kg/min, P < 0.0001). The slope
      and the intercept coincided with the line of identity (Passing and Bablock
      analysis, P = 0.50). Residuals were normally distributed, and the examination of
      the Bland-Altman analysis do not show systematic or proportional error.
      CONCLUSIONS: A moderate and self-regulated 500-m treadmill-walking test is a
      valid tool for VO2peak estimation in patients with HFrEF. These findings may have
      practical implications in the context of transitioning from clinically based
      programs to fitness facilities or self-guided exercise programs in adults and
      elderly men with HFrEF.

PMID- 29661151
TI  - N-terminal pro-B-type natriuretic peptide and microsize myocardial infarction
      risk in the reasons for geographic and racial differences in stroke study.
AB  - BACKGROUND: N-terminal pro B-type peptide (NT-proBNP) has been associated with
      risk of myocardial infarction (MI), but less is known about the relationship
      between NT-proBNP and very small non ST-elevation MI, also known as microsize MI.
      These events are now routinely detectable with modern troponin assays and are
      emerging as a large proportion of all MI. Here, we sought to compare the
      association of NT-proBNP with risk of incident typical MI and microsize MI in the
      REasons for Geographic and Racial Differences in Stroke (REGARDS) Study. METHODS:
      The REGARDS Study is a national cohort of 30,239 US community-dwelling black and
      white adults aged >= 45 years recruited from 2003 to 2007. Expert-adjudicated
      outcomes included incident typical MI (definite/probable MI with peak troponin >=
      0.5 MUg/L), incident microsize MI (definite/probable MI with peak troponin < 0.5
      MUg/L), and incident fatal CHD. Using a case-cohort design, we estimated the
      hazard ratio of the outcomes as a function of baseline NT-proBNP. Competing risk
      analyses tested whether the associations of NT-proBNP differed between the risk
      of incident microsize MI and incident typical MI as well as if the association of
      NT-proBNP differed between incident non-fatal microsize MI and incident non-fatal
      typical MI, while accounting for incident fatal coronary heart disease (CHD) as
      well as heart failure (HF). RESULTS: Over a median of 5 years of follow-up, there
      were 315 typical MI, 139 microsize MI, and 195 incident fatal CHD. NT-proBNP was
      independently and strongly associated with all CHD endpoints, with significantly
      greater risk observed for incident microsize MI, even after removing individuals
      with suspected HF prior to or coincident with their incident CHD event.
      CONCLUSION: NT-proBNP is associated with all MIs, but is a more powerful risk
      factor for microsize than typical MI.

PMID- 29661152
TI  - Genetic variability in the sdrD gene in Staphylococcus aureus from healthy nasal
      carriers.
AB  - BACKGROUND: Staphylococcus aureus cell wall anchored Serine Aspartate repeat
      containing protein D (SdrD) is a member of the microbial surface component
      recognising adhesive matrix molecules (MSCRAMMs). It is involved in the bacterial
      adhesion and virulence. However the extent of genetic variation in S. aureus sdrD
      gene within isolates from healthy carriers are not known. The aim of this study
      was to evaluate allelic variation of the sdrD gene among S. aureus from healthy
      nasal carriers. RESULTS: The sdrD A region from 48 S. aureus isolates from
      healthy carriers were analysed and classified into seven variants. Variations in
      the sdrD A region were concentrated in the N2 and N3 subdomains. Sequence
      analysis of the entire sdrD gene of representative isolates revealed variations
      in the SD repeat and the EF motifs of the B repeat. In silico structural
      modelling indicates that there are no differences in the SdrD structure of the 7
      variants. Variable amino acid residues mapped onto the 3D structure revealed that
      the variations are surface located, exist within the groove between the N2-N3
      subdomains and distributed mainly on the N3 subdomain. Comparison of adhesion to
      keratinocytes in an in vitro cell adhesion assay, using NCTC 8325-4?sdrD strains
      expressing the various sdrD gene variants, indicated a significant difference
      between only two complements while others showed no major difference in their
      adhesion. CONCLUSIONS: This study provides evidence of sequence variations across
      the different domains of SdrD from S. aureus isolated from healthy nasal
      carriers. Proper understanding of these variations is necessary in the study of
      S. aureus pathogenesis.

PMID- 29661153
TI  - Improved analgesia and reduced post-operative nausea and vomiting after
      implementation of an enhanced recovery after surgery (ERAS) pathway for total
      mastectomy.
AB  - BACKGROUND: Enhanced Recovery After Surgery (ERAS) pathways have been shown in
      multiple surgical disciplines to improve outcomes, including reduced opioid
      consumption, length of stay, and post-operative nausea and vomiting (PONV).
      However, very few studies describe the application of ERAS to breast surgery and
      even fewer describe ERAS for outpatient surgery. We describe the implementation
      and efficacy of an Enhanced Recovery After Surgery (ERAS) pathway for total skin
      sparing mastectomy with immediate reconstruction in an outpatient setting.
      METHODS: We implemented an evidence-based, multimodal ERAS pathway for all
      patients undergoing total skin-sparing mastectomy surgery with immediate
      reconstruction at a single 23-h stay surgery center. Highlights of the ERAS
      pathway included: preoperative acetaminophen, gabapentin, and scopolamine;
      regional anesthesia for the breast (Pectoral blocks type 1 and 2 or paravertebral
      block); and intraoperative dexamethasone and ondansetron. This retrospective
      study included all American Society of Anesthesiology (ASA) Class 1-3 patients
      undergoing total skin-sparing mastectomy surgery with immediate reconstruction
      between July 2013 and April 2016. We compared 96 patients who were in the ERAS
      pathway (ERAS group) to a retrospective cohort of 276 patients (Pre group). The
      primary outcome was total perioperative opioid consumption. Secondary outcomes
      were highest postoperative pain scores, incidence of PONV, and length of stay.
      RESULTS: Patients in the ERAS group had significantly lower total perioperative
      opioid consumption compared to the Pre group (mean (SD): 111.4 mg (46.0) vs.
      163.8 mg (73.2) oral morphine equivalents, p < 0.001). Patients in the ERAS group
      also had a lower incidence of PONV (28% vs. 50%, p < 0.001). Patients in the ERAS
      group reported less pain in the recovery room, with a two-point decrease in
      highest pain score (median [interquartile range (IQR)]: 4 [2,6] in ERAS group vs.
      6 [4,7] in Pre group, p < 0.001). There was no clinically significant difference
      in length of stay (median [IQR]: 1144 min [992, 1259] in ERAS group vs. 1188
      [1058, 1344] in Pre group, p = 0.006). CONCLUSION: Implementation of an ERAS
      pathway for total skin-sparing mastectomy with reconstruction that incorporates
      regional anesthesia is feasible in a 23-h-stay hospital. Patients in the ERAS
      pathway had improved post-operative analgesia and reduced post-operative nausea
      and vomiting.

PMID- 29661154
TI  - Cross-sectional and longitudinal factors influencing physical activity of 65 to
      75-year-olds: a pan European cohort study based on the survey of health, ageing
      and retirement in Europe (SHARE).
AB  - BACKGROUND: The promotion of physical activity (PA) plays a major role for
      healthy ageing even in older age. There is a lack of cross-sectional and
      longitudinal studies explicitly dealing with barriers and drivers to PA in older
      adults. Therefore the aims of this study are a) to determine the prevalence of
      insufficient physical activity (IPA) in 65 to 75-year-olds in Europe and to
      identify factors associated with IPA in cross-section and b) to identify
      longitudinal risk factors for IPA in prior active persons. METHODS: This study is
      using data of the Survey of Health, Ageing and Retirement in Europe (SHARE).
      SHARE is a cross-national panel database including individual data of the non
      institutionalised population aged 50+ from 27 European countries. For the present
      paper, we included a cohort that participated in all first four waves of SHARE
      (2004-2011) aged 65-to-75-years at wave four (male n = 1761, female n = 2085)
      from 10 European countries. To identify cross-sectional and longitudinal
      associations, we calculated prevalence odds ratios and hazard ratios with 95%
      confidence intervals. RESULTS: The prevalence of IPA in 65-75-year-olds varied
      widely between countries, ranging from 55.4% to 83.3% in women and from 46.6% to
      73.7% in men. IPA was associated with several intrapersonal factors and strength
      of association was similar for men and women for almost all investigated factors.
      Statistically significant associated with IPA were socioeconomic factors as low
      educational level (own and parental) and financial difficulties (male: POR: 1.60:
      95%-CI: 1.26-2.03; female: POR: 1.58; 95%-CI: 1.26-1.97) and health-related
      factors as e.g. number of chronic diseases (male: POR: 1.34: 95%-CI: 1.23-1.45;
      female: POR: 1.31; 95%-CI: 1.21-1.42). Interpersonal only the size of social
      network was associated with IPA (male and female: POR: 0.88, 95%-CI: 0.81-0.95).
      Longitudinally in a fully adjusted model, only grip strength (HR: 0.99; CI-95%:
      0.98-0.99) and BMI (HR: 1.02; CI-95%: 1.00-1.04) were statistically significant
      risk factors for IPA. CONCLUSIONS: PA promotion programs for older adults should
      incorporate the heterogeneity of health status and physical condition that can
      typically occur in this age group.

PMID- 29661155
TI  - Association between serum levels of caspase-cleaved cytokeratin-18 and early
      mortality in patients with severe spontaneous intracerebral hemorrhage.
AB  - BACKGROUND: Apoptotic changes after cerebral hemorrhage in brain samples of
      humans have been found. Caspase-cleaved cytokeratin (CCCK)-18 could be detected
      in the bloodstream during apoptosis. Higher circulating CCCK-18 levels have been
      associated with 6-month mortality in patients with basal ganglia hemorrhage. The
      aim of our study was to determine whether there is an association between serum
      CCCK-18 levels and early mortality of spontaneous intracerebral hemorrhage (SIH)
      patients. We performed an observational, prospective and multicentre study. There
      were included patients with severe SIH defined as Glasgow Coma Scale (GCS) lower
      than 9. We determined serum CCCK-18 levels at the severe SIH diagnosis moment.
      RESULTS: We found that non-surviving SIH patients (n = 46) showed lower GCS, and
      higher serum CCCK-18 levels and APACHE-II score than survivor ones (n = 54). In
      ROC analysis was found that the area under the curve of serum CCCK-18 levels for
      30-day mortality prediction was 90% (95% CI 82-95%; p < 0.001). In the multiple
      logistic regression analysis, we found an association between serum CCCK-18
      levels and 30-day mortality (OR 1.034; 95% CI 1.013-1.055; p = 0.002).
      CONCLUSIONS: The novel finding of our study was that there is an association
      between high serum CCCK-18 levels and 30-day mortality in severe SIH patients.

PMID- 29661156
TI  - SYNERGIC TRIAL (SYNchronizing Exercises, Remedies in Gait and Cognition) a multi
      Centre randomized controlled double blind trial to improve gait and cognition in
      mild cognitive impairment.
AB  - BACKGROUND: Physical exercise, cognitive training, and vitamin D are low cost
      interventions that have the potential to enhance cognitive function and mobility
      in older adults, especially in pre-dementia states such as Mild Cognitive
      Impairment (MCI). Aerobic and progressive resistance exercises have benefits to
      cognitive performance, though evidence is somewhat inconsistent. We postulate
      that combined aerobic exercise (AE) and progressive resistance training (RT)
      (combined exercise) will have a better effect on cognition than a balance and
      toning control (BAT) intervention in older adults with MCI. We also expect that
      adding cognitive training and vitamin D supplementation to the combined exercise,
      as a multimodal intervention, will have synergistic efficacy. METHODS: The
      SYNERGIC trial (SYNchronizing Exercises, Remedies in GaIt and Cognition) is a
      multi-site, double-blinded, five-arm, controlled trial that assesses the
      potential synergic effect of combined AE and RT on cognition and mobility, with
      and without cognitive training and vitamin D supplementation in older adults with
      MCI. Two-hundred participants with MCI aged 60 to 85 years old will be randomized
      to one of five arms, four of which include combined exercise plus combinations of
      dual-task cognitive training (real vs. sham) and vitamin D supplementation (3 *
      10,000 IU/wk. vs. placebo) in a quasi-factorial design, and one arm which
      receives all control interventions. The primary outcome measure is the ADAS-Cog
      (13 and plus modalities) measured at baseline and at 6 months of follow-up.
      Secondary outcomes include neuroimaging, neuro-cognitive performance, gait and
      mobility performance, and serum biomarkers of inflammation (C reactive protein
      and interleukin 6), neuroplasticity (brain-derived neurotropic factor),
      endothelial markers (vascular endothelial growth factor 1), and vitamin D serum
      levels. DISCUSSION: The SYNERGIC Trial will establish the efficacy and
      feasibility of a multimodal intervention to improve cognitive performance and
      mobility outcomes in MCI. These interventions may contribute to new approaches to
      stabilize and reverse cognitive-mobility decline in older individuals with MCI.
      TRIAL REGISTRATION: Identifier: NCT02808676.
      https://www.clinicaltrials.gov/ct2/show/NCT02808676 .

PMID- 29661157
TI  - Sub-inhibitory concentrations of oxacillin modify the expression of agr locus in
      Staphylococcus aureus clinical strains belonging to different clonal complexes.
AB  - BACKGROUND: The ability of Staphylococcus aureus to invade tissues and cause an
      infectious disease is the result of a multi-factorial process supported by the
      huge number of virulence factors inherent to this microorganism tightly regulated
      by the accessory gene regulator (agr). During antimicrobial therapy bacteria may
      be exposed to sub-inhibitory concentrations (subMICs) of antibiotics that may
      trigger transcriptional changes that may have an impact on the pathogenesis of
      infection. The objective of this study was to investigate the effect of oxacillin
      sub-MICs on agr system expression as the key component in the regulation of
      virulence in methicillin-susceptible (MSSA) and -resistant S. aureus (MRSA)
      strains. Furthermore, we studied the genetic basis of the agr locus and their
      potential association with the expression levels. METHODS: We have examined the
      expression of RNAIII and agrA mRNA as biomarkers for agr expression in the
      presence and absence of oxacillin subMICs in 10 MSSA and 4 MRSA clinical strains
      belonging to 5 clonal complexes (CC45-agrI, CC8-agrI, CC5-agrII, CC15-agrII and
      CC30-agrIII) causing endovascular complications. The DNA sequences of agr locus
      were obtained by whole genome sequencing. RESULTS: Our results revealed that
      exposure to subMICs of oxacillin had an impact on agr locus expression modifying
      the relative levels of expression with increases in 11 strains and with decreases
      in 3 strains. Thereby, the exposure to subMICs of oxacillin resulted in higher
      levels of expression of agr in CC15 and CC45 and lower levels in CC30. We also
      observed the presence of mutations in agrC and agrA in 13/14 strains with similar
      mutation profiles among strains within individual CCs except for strains of CC5.
      Although, agr expression levels differed among strains within CCs, the presence
      of these mutations was associated with differences in agr expression levels in
      most cases. CONCLUSIONS: Changes in agr expression induced by exposure to
      oxacillin subMICs should be considered because they could lead to changes in the
      virulence modulation and have an adverse effect on the course of infection,
      especially in certain clonal complexes.

PMID- 29661158
TI  - Effect of an intervention targeting inappropriate continued empirical parenteral
      vancomycin use: a quasi-experimental study in a region of high MRSA prevalence.
AB  - BACKGROUND: Despite vancomycin use is a major risk factor for the emergence of
      vancomycin resistance, it is frequently inappropriately prescribed, especially as
      empirical treatment. We evaluated the effect of an antimicrobial stewardship
      intervention targeting for inappropriate continued empirical vancomycin use.
      METHODS: This was a quasi-experimental study comparing vancomycin use in a 6
      month pre-intervention and 6-month intervention period. If empirical vancomycin
      was continued for more than 96 h without documentation of beta-lactam-resistant
      gram-positive microorganisms, it was considered inappropriate continued empirical
      vancomycin use. The intervention consisted of the monitoring of appropriateness
      by a pharmacist and direct discussion with the prescribing physicians by
      infectious disease specialists when empirical vancomycin was continued
      inappropriately. An interrupted time series analysis was used to compare
      vancomycin use before and during the intervention. RESULTS: Following
      implementation of the intervention, overall vancomycin consumption decreased by
      14.6%, from 37.6 defined daily doses (DDDs)/1000 patient-days in the pre
      intervention period to 32.1 DDDs/1000 patient-days in the intervention period (P
      <  0.001). The inappropriate consumption of vancomycin also declined from 8.0
      DDDs/1000 patient-days to 5.8 DDDs/1000 patient-days (P = 0.009). CONCLUSION:
      Interventions such as direct communication with prescribing physicians and
      infectious disease clinicians can help reduce the inappropriate continued use of
      vancomycin.

PMID- 29661159
TI  - Active DNA end processing in micronuclei of ovarian cancer cells.
AB  - BACKGROUND: Ovarian cancer is one of the most deadly gynecological malignancies
      and inclined to recurrence and drug resistance. Previous studies showed that the
      tumorigenesis of ovarian cancers and their major histotypes are associated with
      genomic instability caused by defined sets of pathogenic mutations. In contrast,
      the mechanism that influences the development of drug resistance and disease
      recurrence is not well elucidated. Solid tumors are prone to chromosomal
      instability (CIN) and micronuclei formation (MN). Although MN is traditionally
      regarded as the outcome of genomic instability, recent investigation on its
      origin and final consequences reveal that the abnormal DNA metabolism in MN is a
      driver force for some types of catastrophic genomic rearrangements, accelerating
      dramatic genetic variation of cancer cells. METHODS: We used Indirect
      Immunofluorescent staining to visualize micronuclei and activation of DNA repair
      factors in ovarian cancer cell lines and biopsies. RESULTS: We show that ovarian
      cancer cells are disposed to form micronuclei upon genotoxic insults. Double
      strand DNA breaks (DSBs)-triggered insurgence of micronuclei is associated with
      unrepaired chromosomes passing through mitosis. According to their morphology and
      DNA staining, micronuclei compartments are divided into early and late stages
      that can be further characterized by differential staining of gammaH2AX and
      53BP1. We also show that MN compartments do not halt controlled DNA metabolism as
      sequestered nuclear repair factors are enriched at DNA breaks in MN compartments
      and efficiently process DNA ends to generate single-stranded DNA (ssDNA)
      structures. Interestingly, unknown factors are required for DNA end processing in
      MN in addition to the nuclear resection machinery. Finally, these hallmarks of
      micronuclei evolution depicted in cell culture were recapitulated in different
      stages of ovarian cancer biopsies. CONCLUSIONS: In aggregate, our findings
      demonstrate that ovarian cancer cells are inclined to form micronuclei that
      undergo robust DNA metabolism and generate ssDNA structures, potentially
      destabilizing genomic structures and triggering genetic variation.

PMID- 29661160
TI  - Characterizing the experience of agitation in patients with bipolar disorder and
      schizophrenia.
AB  - BACKGROUND: Agitation is a common manifestation of bipolar disorder and
      schizophrenia which includes symptoms ranging from inner tension and unease to
      violence and aggression. Much of the existing literature has focused on agitation
      in the acute setting, with the patient experience poorly defined. Thus, the aim
      of this study was to characterize agitation and its management from a patient
      perspective, with the focus on those who reside in the community. METHODS:
      Surveys were completed across Germany, Spain and the UK by 583 community dwelling
      patients with schizophrenia or bipolar disorder who experienced episodes of
      agitation. Patients were recruited via either their physician or through patient
      support groups. The survey captured information on demographics, disease
      characteristics, frequency of agitation episodes and different pre-defined
      severity levels ranging from mild to severe, symptoms experienced during an
      episode, awareness of agitation and coping strategies employed by the patient.
      Statistics were descriptive in nature. RESULTS: The most commonly reported
      symptoms during an episode of agitation were feeling uneasy (n = 373, 64%),
      restless (n = 368, 63%) or nervous (n = 368, 63%). Patients experienced an
      average of 22.4 (SD 57.2) mild, 15.4 (SD 61.2) moderate, 6.8 (SD 63.3) moderate
      intense and 2.9 (SD 24.4) severe episodes within the last 12 months; on average
      2.7 (SD 6.8) required hospital attendance. Half of patients (n = 313) had
      attended hospital due to agitation. In total, 71% of patients (n = 412) were
      aware they were becoming agitated either always or sometimes and 61% of patients
      (n = 347) were aware of agitation triggers either always or sometimes. The
      majority of patients reported being able to sometimes control their agitation
      (56%, n = 329) but 16% (n = 94) stated that there is typically nothing they can
      do. To cope with episodes 55% (n = 125) of schizophrenia patients and 66% (n =
      234) of bipolar disorder patients reported taking prescribed medication.
      CONCLUSION: Community based patients with schizophrenia and bipolar disorder
      reported frequently experiencing agitation episodes which they defined most
      commonly as feeling uneasy, restless or nervous. A range of coping strategies
      were reported but they were not always successful, highlighting an area of unmet
      need in this population.

PMID- 29661161
TI  - Absolute income is a better predictor of coverage by skilled birth attendance
      than relative wealth quintiles in a multicountry analysis: comparison of 100 low-
      and middle-income countries.
AB  - BACKGROUND: Having high-quality data available by 2020, disaggregated by income,
      is one of the Sustainable Development Goals (SGD). We explored how well coverage
      with skilled birth attendance (SBA) is predicted by asset-based wealth quintiles
      and by absolute income. METHODS: We used data from 293 national surveys conducted
      in 100 low and middle-income countries (LMICs) from 1991 to 2014. Data on
      household income were computed using national income levels and income inequality
      data available from the World Bank and the Standardized World Income Inequality
      Database. Multivariate regression was used to explore the predictive capacity of
      absolute income compared to the traditional measure of quintiles of wealth index.
      RESULTS: The mean SBA coverage was 68.9% (SD: 24.2), compared to 64.7% (SD: 26.6)
      for institutional delivery coverage. Median daily family income in the same
      period was US$ 6.4 (IQR: 3.5-14.0). In cross-country analyses, log absolute
      income predicts 51.5% of the variability in SBA coverage compared to 22.0%
      predicted by the wealth index. For within-country analysis, use of absolute
      income improved the understanding of the gap in SBA coverage among the richest
      and poorest families. Information on income allowed identification of countries -
      such as Burkina Faso, Cambodia, Egypt, Nepal and Rwanda - which were well above
      what would be expected solely from changes in income. CONCLUSION: Absolute income
      is a better predictor of SBA and institutional delivery coverage than the
      relative measure of quintiles of wealth index and may help identify countries
      where increased coverage is likely due to interventions other than increased
      income.

PMID- 29661162
TI  - The cold pressor test in interictal migraine patients - different parasympathetic
      pupillary response indicates dysbalance of the cranial autonomic nervous system.
AB  - BACKGROUND: Data on autonomic nervous system (ANS) activations in migraine
      patients are quite controversial, with previous studies reporting over- and
      underactivation of the sympathetic as well as parasympathetic nervous system. In
      the present study, we explicitly aimed to assess the cranial ANS in migraine
      patients compared to healthy controls by applying the cold pressor test to a
      cohort of migraine patients in the interictal phase and measuring the pupillary
      response. METHODS: In this prospective observational study, a strong sympathetic
      stimulus was applied to 20 patients with episodic migraine in the interictal
      phase and 20 matched controls without migraine, whereby each participant dipped
      the left hand into ice-cold (4  degrees C) water for a maximum of 5 min (cold
      pressor test). At baseline, 2, and 5 min during the cold pressor test, infrared
      monocular pupillometry was applied to quantify pupil diameter and light reflex
      parameters. Simultaneously, heart rate and blood pressure were measured by the
      external brachial RR-method at distinct time intervals to look for at least
      clinically relevant changes of the cardiovascular ANS. RESULTS: There were no
      significant differences between the migraine patients and controls at baseline
      and after 2 min of sympathetic stimulation in all the measured pupillary and
      cardio-vascular parameters. However, at 5 min, pupillary light reflex (PLR)
      constriction velocity was significantly higher in migraineurs than in controls
      (5.59 +/- 0.73 mm/s vs. 5.16 +/- 0.53 mm/s; unpaired t-test p < 0.05), while both
      cardiovascular parameters and PLR dilatation velocity were similar in both groups
      at this time point. CONCLUSIONS: Our findings of an increased PLR constriction
      velocity after sustained sympathetic stimulation in interictal migraine patients
      suggest an exaggerated parasympathetic response of the cranial ANS. This
      indicates that brainstem parasympathetic dysregulation might play a significant
      role in migraine pathophysiology. More dedicated examination of the ANS in
      migraine patients might be of value for a deeper understanding of its
      pathophysiology.

PMID- 29661163
TI  - Characteristics of keratoconic patients at two main eye centres in Palestine: a
      cross-sectional study.
AB  - BACKGROUND: Keratoconus (KC) is a multifactorial, degenerative ectatic condition
      of the cornea. It usually manifests during late adolescence or the early
      twenties. A painless disease, KC may end with severe visual loss. The prevalence
      of KC in middle-eastern countries is much higher than in other regions of the
      world. This may be due to genetic and environmental risk factors and
      consanguinity. The goal of this study is to explore the demographic profile of
      Palestinian keratoconic patients. METHODS: A retrospective study was conducted in
      two ophthalmology centres (Tertiary Ophthalmic Centre of An-Najah National
      University Hospital and An-Noor Centre at the Specialized Arab Hospital). All
      medical charts of keratoconic patients attending both centres over the period
      from 2009 to 2016 were reviewed. These patients were diagnosed by
      ophthalmologists depending on history, examination and Pentacam. Severity was
      determined using the k median index from the Pentacam map. Data analysis was
      carried out using SPSS Version 22. RESULTS: The medical files of 936 keratoconic
      eyes of 505 keratoconic patients were reviewed. Their mean age at the time of
      diagnosis was 23.3 ranging from 8 to 62 years. Approximately 70.1% of them
      presented after the age of 20 years, and younger age groups were more likely to
      develop a severe disease stage than older ones (P = 0.001, r = - 0.108). There
      was a nearly equal distribution of patients between the two sexes (49.5% male,
      50.5% female). On initial evaluation, the best-corrected visual acuity (BCVA) was
      recorded as >=6/12 in most affected eyes (71.5%). Regarding severity, 62%
      presented in a mild form, while 9.9% were at a severe stage. About 88.2%
      presented with bilateralism. CONCLUSIONS: Most of the patients in their twenties
      presented with a mild bilateral form of the disease. This result is compatible
      with published international reports. It is recommended that the results of this
      study be considered when establishing a screening program in Palestine.
      Subsequently, patients will be identified at an appropriate time where action can
      be taken before disease progression take place.

PMID- 29661164
TI  - Helicase-like transcription factor expression is associated with a poor prognosis
      in Non-Small-Cell Lung Cancer (NSCLC).
AB  - BACKGROUND: The relapse rate in early stage non-small cell lung cancer (NSCLC)
      after surgical resection is high. Prognostic biomarkers may help identify
      patients who may benefit from additional therapy. The Helicase-like Transcription
      Factor (HLTF) is a tumor suppressor, altered in cancer either by gene
      hypermethylation or mRNA alternative splicing. This study assessed the expression
      and the clinical relevance of wild-type (WT) and variant forms of HLTF RNAs in
      NSCLC. METHODS: We analyzed online databases (TCGA, COSMIC) for HLTF alterations
      in NSCLC and assessed WT and spliced HLTF mRNAs expression by RT-ddPCR in 39 lung
      cancer cell lines and 171 patients with resected stage I-II NSCLC. RESULTS: In
      silico analyses identified HLTF gene alterations more frequently in lung squamous
      cell carcinoma than in adenocarcinoma. In cell lines and in patients, WT and I21R
      HLTF mRNAs were detected, but the latter at lower level. The subgroup of 25
      patients presenting a combined low WT HLTF expression and a high I21R HLTF
      expression had a significantly worse disease-free survival than the other 146
      patients in univariate (HR 1.96, CI 1.17-3.30; p = 0.011) and multivariate
      analyses (HR 1.98, CI 1.15-3.40; p = 0.014). CONCLUSION: A low WT HLTF expression
      with a high I21R HLTF expression is associated with a poor DFS.

PMID- 29661165
TI  - Midwives' perceptions on using a fetoscope and Doppler for fetal heart rate
      assessments during labor: a qualitative study in rural Tanzania.
AB  - BACKGROUND: The Doppler is thought to be more comfortable and effective compared
      to the fetoscope for assessing the fetal heart rate (FHR) during labor. However,
      in a rural Tanzanian hospital, midwives who had easy access to both devices
      mostly used fetoscope. This study explored midwives' perception of factors
      influencing their preference for using either a Pinard fetoscope or a FreePlay
      wind-up Doppler for intermittent FHR monitoring. METHODS: Midwives who had worked
      for at least 6 months in the labor ward were recruited. Focus group discussion
      (FGD) was used to collect data. Five FGDs were conducted between December 2015
      and February 2016. Qualitative content analysis was employed using NVivo 11.0.
      RESULTS: Three main themes emerged as factors perceived by midwives as
      influencing their preference; 1) Sufficient training and experience with using a
      device; Midwives had been using fetoscopes since their midwifery training, and
      they had vast experience using it. The Doppler was recently introduced in the
      maternity ward, and midwives had insufficient training in how to use it. 2)
      Ability of the device to produce reliable measurements; Using a fetoscope, one
      must listen for the heartbeat, count using a watch, and calculate, the Doppler
      provides both a display and sound of the FHR. Fetoscope measurements are prone to
      human errors, and Doppler measurements are prone to instrumental errors. 3)
      Convenience of use and comfort of a device; Fetoscopes do not need charging, and
      while it is possible to "personalize/hide" the measurements, and may be painful
      for mothers. Dopplers need charging and do not cause pain, but provide limited
      privacy. CONCLUSION: Midwives' preferences of FHR monitoring devices are
      influenced by the level of device training, experience with using a device,
      reliable measurements, and convenience and comfort during use. Fetoscopes and
      Dopplers should be equally available during midwifery training and in clinical
      practice.

PMID- 29661166
TI  - High OX40 expression in recurrent ovarian carcinoma is indicative for response to
      repeated chemotherapy.
AB  - BACKGROUND: Ovarian carcinoma (OC) is the fifth most common female cancer and
      mostly diagnosed at an advanced stage. Surgical debulking is usually followed by
      adjuvant platinum-based chemotherapy. Only few biomarkers are known to be related
      to chemosensitivity. OX40 is a TNF receptor member and expressed on activated
      CD4+ and CD8+ T cells. It is known that OX40 signaling promotes survival and
      responds to various immune cells of the innate and adaptive immune system.
      Therefore we investigated the indicative value of OX40 expression for recurrence
      and survival in OC. METHODS: A tissue microarray of biopsies of mostly high-grade
      primary serous OC and matched recurrences of 47 patients was stained with OX40.
      Recurrence within 6 months of the completion of platinum-based chemotherapy was
      defined as chemoresistance. RESULTS: Chemosensitivity correlated significantly
      with high OX40 positive immune cell density in primary cancer biopsies (p =
      0.027). Furthermore patients with a higher OX40 expression in recurrent cancer
      biopsies showed a better outcome in recurrence free survival (RFS) (p = 0.017)
      and high OX40 expression was associated with chemosensitivity (p = 0.008). OX40
      positive TICI in recurrent carcinomas significantly correlated with IL-17
      positive tumor infiltrating immune cells in primary carcinomas (r s  = 0.34; p =
      0.023). Univariate cox regression analysis revealed a significant longer RFS and
      higher numbers of chemotherapy cycles for high OX40 tumor cell expression in
      recurrent cancer biopsies (HR 0.39, 95%CI 0.16-0.94, p = 0.036 and 1.28, 95%CI
      1.05-1.55; p = 0.013). CONCLUSION: High OX40 expression in OC is correlated with
      chemosensitivity and improved RFS in OC. Patients might therefore benefit from a
      second line therapy.

PMID- 29661167
TI  - Creating an Optimality Index - Netherlands: a validation study.
AB  - BACKGROUND: At present, the maternity care system in the Netherlands is being
      reorganized into an integrated model of care, shifting the focus of midwives to
      include increasing numbers of births in hospital settings and clients with medium
      risk profiles. In light of these changes, it is useful for midwives to have a
      tool which may help them in reflecting upon care practices that promote
      physiological childbirth practices. The Optimality Index-US is an evidence based
      tool, designed to measure optimal perinatal care processes and outcomes. It has
      been validated for use in the United States (OI-US), United Kingdom (OI-UK) and
      Turkey (OI-TR). The objective of this study was to adapt the OI-US for the Dutch
      maternity care setting (OI-NL). METHODS: Translation and back translation were
      applied to create the OI-NL. A panel of maternity care experts (n = 10) provided
      input for face validation items in the OI-NL. Assessment of inter-rater
      reliability and ease of use was also conducted. Following this, the OI-NL was
      used prospectively to collect data on 266 women who commenced intrapartum care
      under the responsibility of a midwife. Twice groups were compared, based on
      parity and on care-setting at birth. Mean scores between these groups, corrected
      for perinatal background factors were assessed for discriminant validity.
      RESULTS: Face validity was established for OI-NL on the basis of expert input.
      Discriminant validity was confirmed by conducting multiple regressions analyses
      for parity (beta = 6.21, P = 0.00) and for care-setting (beta = 12.1, p = 0.00).
      Inter-rater reliability was 98%, with one item (Apgar score) sensitive to scoring
      differences. CONCLUSION: OI-NL is a valid and reliable tool for use in the Dutch
      maternity care setting. In addition to its value for assessing evidence-based
      maternity care processes and outcomes, there is potential for use for learning
      and reflection. Against the backdrop of a changing maternity care system, and due
      to the specificity of its items OI-NL may be of value as a tool for detecting
      subtle changes indicative of escalating medicalization of childbirth in the
      Netherlands.

PMID- 29661168
TI  - Working to improve the management of sarcoma patients across Europe: a policy
      checklist.
AB  - BACKGROUND: The Sarcoma Policy Checklist was created by a multidisciplinary
      expert group to provide policymakers with priority areas to improve care for
      sarcoma patients. MAIN BODY: This paper draws on this research, by looking more
      closely at how France, Germany, Italy, Spain, Sweden and the United Kingdom are
      addressing each of these priority areas. It aims to highlight key gaps in
      research, policy and practice, as well as ongoing initiatives that may impact the
      future care of sarcoma patients in different European countries. A pragmatic
      review of the published and web-based literature was undertaken. Telephone
      interviews were conducted in each country with clinical and patient experts to
      substantiate findings. Research findings were discussed within the expert group
      and developed into five core policy recommendations. The five identified priority
      areas were: the development of designated and accredited centres of reference;
      more professional training; multidisciplinary care; greater incentives for
      research and innovation; and more rapid access to effective treatments. Most of
      the countries studied have ongoing initiatives addressing many of these
      priorities; however, many are in early stages of development, or require
      additional funding and resources. CONCLUSION: Gaps in access to quality care are
      particularly concerning in many of Europe's lower-resourced countries. Equitable
      access to information, clinical trials, innovative treatments and quality
      specialist care should be available to all sarcoma patients. Achieving this
      across Europe will require close collaboration between all stakeholders at both
      the national and European level.

PMID- 29661170
TI  - "People look and ask lots of questions": caregivers' perceptions of healthcare
      provision and support for children born with cleft lip and palate.
AB  - BACKGROUND: Clefting of the lip and/or palate (CL/P) is amongst the five most
      common birth defects reported in South Africa. The emotional impact on parents at
      the birth of their new-born with CL/P could affect parent-child relationships. In
      light of insufficient scholarly attention parental experiences and perceptions,
      this study reports on caregivers' perceptions of health service provision and
      support for children born with cleft lip and palate in South Africa. METHODS: The
      study setting consisted of 11 academic hospital centres situated in six of South
      Africa's nine provinces. At each of the academic centres cleft clinic, five to
      ten parents or caregivers were selected purposively. Participants were
      interviewed, using a semi-structured interview schedule that elicited socio
      demographic information, explored the family experiences of having a child with
      CL/P, and their perceptions of care provision and support services available. The
      interviews were analysed using thematic content analysis. RESULTS: Seventy-nine
      participants were interviewed. Their mean age was 33.3 years (range 17-68 years).
      The majority of the parents were black African (72%), unemployed (72%), single
      (67%) and with only primary school education (58%). The majority of the children
      were male, with a mean age of 3.8 (SD = +/-4.3) years. Five broad themes emerged
      from the interviews: emotional experiences following the birth of a child with
      cleft lip and palate; reactions from family, friends or the public; the burden of
      care provision; health system responsiveness; and social support services.
      Caregivers reported feelings of shock, anxiety, and sadness, exacerbated by the
      burden of care provision, health system deficiencies, lack of public awareness
      and insufficient social support services. CONCLUSIONS: The findings have
      implications for the integrated management of children with cleft lip and/or
      palate, including information to parents, the education and training of
      healthcare providers, raising public awareness of birth defects, and social
      support.

PMID- 29661169
TI  - RNA-Seq reveals the existence of a CDKN1C-E2F1-TP53 axis that is altered in human
      T-cell lymphoblastic lymphomas.
AB  - BACKGROUND: Precursor T-cell lymphoblastic lymphomas (T-LBL) are rare aggressive
      hematological malignancies that mainly develop in children. As in other cancers,
      the loss of cell cycle control plays a prominent role in the pathogenesis in
      these malignancies that is primarily attributed to loss of CDKN2A (encoding
      protein p16INK4A). However, the impact of the deregulation of other genes such as
      CDKN1C, E2F1, and TP53 remains to be clarified. Interestingly, experiments in
      mouse models have proven that conditional T-cell specific deletion of Cdkn1c gene
      may induce a differentiation block at the DN3 to DN4 transition, and that the
      loss of this gene in the absence of Tp53 led to aggressive thymic lymphomas.
      RESULTS: In this manuscript, we demonstrated that the simultaneous deregulation
      of CDKN1C, E2F1, and TP53 genes by epigenetic mechanisms and/or the deregulation
      of specific microRNAs, together with additional impairing of TP53 function by the
      expression of dominant-negative isoforms are common features in primary human T
      LBLs. CONCLUSIONS: Previous experimental work in mice revealed that T-cell
      specific deletion of Cdkn1c accelerates lymphomagenesis in the absence of Tp53.
      If, as expected, the consequences of the deregulation of the CDKN1C-E2F1-TP53
      axis were the same as those experimentally demonstrated in mouse models, the
      disruption of this axis might be useful to predict tumor aggressiveness, and to
      provide the basis towards the development of potential therapeutic strategiesin
      human T-LBL.

PMID- 29661171
TI  - A novel TEX11 mutation induces azoospermia: a case report of infertile brothers
      and literature review.
AB  - BACKGROUND: Testis-expressed gene 11 (TEX11) is an X-linked gene and essential
      for meiotic recombination and chromosomal synapsis. TEX11 deficiency causes
      meiotic arrest and male infertility, and many TEX11 mutations have been found in
      azoospermic and infertile men. CASE PRESENTATION: This study reported one novel
      TEX11 mutation (2653G -> T, in exon 29, GenBank accession number, NM_031276) in
      two brothers with azoospermia. This mutation was firstly screened out by whole
      exome sequencing (WES) and further verified by amplifying and sequencing the
      specific exon 29. Surprisingly, the same exonic missense mutation (W856C) was
      observed in two brothers but not in their mother. Histological analysis of
      testicular biopsy from both brothers revealed meiotic arrest and no post-meiotic
      round spermatids and mature spermatozoa were observed in the seminiferous
      tubules. TEX11 expression was observed strongly in spermatogonia and weakly in
      spermatocytes, but not in Sertoli cells and interstitial cells. CONCLUSIONS: We
      identified one novel TEX11 mutation in two brothers and summarized the literature
      regarding TEX11 mutations and male infertility. This study and previous
      literature indicate that TEX11 mutations are closely associated with male
      infertility, especially azoospermia, although auxiliary clinical analyses are
      needed to figure out the causes of male infertility.

PMID- 29661173
TI  - Predictors of elevated capillary blood glucose in overweight railway French
      employees: a cross-sectional analysis.
AB  - BACKGROUND: Hyperglycaemia is a risk factor of cardiovascular disease and a high
      risk state for progression to type 2 diabetes. Moreover, overweight, defined as a
      body mass index (BMI) between 25 and 29.9 kg/m2, increases the risk of diabetes.
      Information about the feasibility of measuring, during routine occupational
      health examinations, predictors of elevated capillary blood glucose in overweight
      individuals is scarce. This study aims to identify factors that are associated
      with elevated capillary blood glucose and can be routinely measured in French
      overweight employees to develop targeted preventive strategies in the workplace.
      METHODS: Cross-sectional study based on data collected during a workplace health
      promotion programme of the French National Railways Company (SNCF) from January
      2011 to March 2015. A self-administered questionnaire was completed by overweight
      volunteers during the routine occupational health examination. Data collected
      included health, anthropometric, sociodemographic, occupational, and lifestyle
      characteristics. Elevated capillary blood glucose was defined as capillary blood
      glucose equal to or higher than 7 mmol/L. Multivariate logistic regression
      analysis was used to examine factors associated with elevated capillary blood
      glucose and results were described with odds ratios (OR) and 95% confidence
      intervals (CI). RESULTS: The analysis concerned 2248 overweight employees (mean
      age: 43 years) with complete data (total population: 7724). The prevalence of
      elevated capillary blood glucose was 20.0%. In the multivariate analysis,
      significant predictors of elevated capillary blood glucose were: male sex (OR
      1.66, 95% CI 1.21-2.28), age >= 50 years (OR 1.61, 95% CI 1.01-2.55), high blood
      pressure (OR 1.35, 95% CI 1.07-1.69), and daily intake of sugary food (OR 1.53,
      95% CI 1.17-2.00). No association with occupational characteristics (work
      schedule, job seniority, professional grade, and job sector) was found possibly
      due to lack of statistical power. CONCLUSIONS: Our findings provide information
      for setting up specific diabetes prevention strategies in the workplace.
      Overweight men, aged 50 and older, with high blood pressure and daily sugary food
      intake should be considered for capillary blood glucose measurements during their
      occupational medical surveillance. Hypertension screening and management as well
      as health policy measures to target sugary food consumption could be included in
      workplace prevention strategies.

PMID- 29661172
TI  - MTH1 deficiency selectively increases non-cytotoxic oxidative DNA damage in lung
      cancer cells: more bad news than good?
AB  - BACKGROUND: Targeted therapies are based on exploiting cancer-cell-specific
      genetic features or phenotypic traits to selectively kill cancer cells while
      leaving normal cells unaffected. Oxidative stress is a cancer hallmark phenotype.
      Given that free nucleotide pools are particularly vulnerable to oxidation, the
      nucleotide pool sanitising enzyme, MTH1, is potentially conditionally essential
      in cancer cells. However, findings from previous MTH1 studies have been
      contradictory, meaning the relevance of MTH1 in cancer is still to be determined.
      Here we ascertained the role of MTH1 specifically in lung cancer cell
      maintenance, and the potential of MTH1 inhibition as a targeted therapy strategy
      to improve lung cancer treatments. METHODS: Using siRNA-mediated knockdown or
      small-molecule inhibition, we tested the genotoxic and cytotoxic effects of MTH1
      deficiency on H23 (p53-mutated), H522 (p53-mutated) and A549 (wildtype p53) non
      small cell lung cancer cell lines relative to normal MRC-5 lung fibroblasts. We
      also assessed if MTH1 inhibition augments current therapies. RESULTS: MTH1
      knockdown increased levels of oxidatively damaged DNA and DNA damage signaling
      alterations in all lung cancer cell lines but not normal fibroblasts, despite no
      detectable differences in reactive oxygen species levels between any cell lines.
      Furthermore, MTH1 knockdown reduced H23 cell proliferation. However,
      unexpectedly, it did not induce apoptosis in any cell line or enhance the effects
      of gemcitabine, cisplatin or radiation in combination treatments. Contrastingly,
      TH287 and TH588 MTH1 inhibitors induced apoptosis in H23 and H522 cells, but only
      increased oxidative DNA damage levels in H23, indicating that they kill cells
      independently of DNA oxidation and seemingly via MTH1-distinct mechanisms.
      CONCLUSIONS: MTH1 has a NSCLC-specific p53-independent role for suppressing DNA
      oxidation and genomic instability, though surprisingly the basis of this may not
      be reactive-oxygen-species-associated oxidative stress. Despite this, overall our
      cell viability data indicates that targeting MTH1 will likely not be an across
      the-board effective NSCLC therapeutic strategy; rather it induces non-cytotoxic
      DNA damage that could promote cancer heterogeneity and evolution.

PMID- 29661174
TI  - Diabetes mellitus and the risk of gastrointestinal cancer in women compared with
      men: a meta-analysis of cohort studies.
AB  - BACKGROUND: The increasing epidemic proportions of diabetes mellitus (DM) are a
      major cause of premature illness and death. However, whether DM confers the same
      excess risk of gastrointestinal cancer for women as it does for men remains
      controversial. The purpose of this study was to estimate the relation between DM
      and gastrointestinal cancer in women compared with men after accounting for other
      major risk factors based on cohort studies. METHODS: We performed a meta-analysis
      of cohort studies published through May 2017 from PubMed, Embase, and the
      Cochrane Library. Studies with cohort designs were stratified by sex and reported
      the relation between DM and esophageal cancer (EC), gastric cancer (GC),
      colorectal cancer (CRC), colon cancer (CC), rectal cancer (RC), hepatocellular
      carcinoma (HCC), or pancreatic cancer (PC) risk. The ratio of relative risk (RRR)
      between men and women was employed to measure the sex differences in the relation
      between DM and gastrointestinal cancer with a random effects model with inverse
      variance weighting. RESULTS: We included 38 cohort studies reporting data on
      18,060,698 individuals. The pooled RRR indicated DM women was associated with an
      increased risk of GC (RRR: 1.14; 95%CI: 1.06-1.22; p < 0.001), while the risk of
      HCC was lower (RRR: 0.88; 95%CI: 0.79-0.99; p = 0.031) as compared with DM men.
      Further, there was no evidence of sex differences in the RRR between participants
      who had DM compared with those without DM for EC (p = 0.068), CRC (p = 0.618),
      and PC (p = 0.976). In addition, the pooled RRR showed a statistically
      significant association between DM and the risk of CC in women compared with men
      (RRR: 0.93; 95%CI: 0.86-1.00; p = 0.050), and there was no evidence of sex
      differences for RC among participants with DM compared to those without DM (p =
      0.648). Finally, the sex differences of the comparison between DM and non-DM for
      gastrointestinal cancer risk at different sites were variable after
      stratification for different effect estimates. CONCLUSIONS: The findings of this
      study suggested female-to-male RRR of DM was increased for GC, while reduced for
      HCC and CC. However, there were no sex differences for the relation between DM
      and the risk of EC, CRC, PC, and RC.

PMID- 29661176
TI  - Spatiotemporal evolution of Chinese ageing from 1992 to 2015 based on an improved
      Bayesian space-time model.
AB  - BACKGROUND: Most countries are experiencing growth in the number and proportion
      of their ageing populations and this issue is posing challenges for economies and
      societies worldwide. The most populated country in the world, China, is
      experiencing a dramatic increase in its ageing population. As China is the
      world's largest developing country, its serious ageing issue may have far
      reaching effects not only domestically but also in other countries and even
      globally. METHODS: In order to overcome the weaknesses of traditional statistical
      models and reveal further detail regarding the local area evolution, an improved
      Bayesian space-time model is presented in this paper and used to estimate the
      spatiotemporal evolution of Chinese ageing from 1992 to 2015. RESULTS: The six
      eastern provinces with high levels of ageing have been experiencing an almost
      steady state, while Jiangsu, Shanghai and Zhejiang have weak increased trends of
      ageing, and the weak increased trend is decreasing. Although the northern and
      western provinces belong to the low ageing area, five of them have strong local
      growth trends and therefore strong potential to exacerbate ageing. Under the
      background of the "comprehensive two children" policy, the forecast value of
      China's ageing rate is 13.80% (95% CI:11.24%,18.83% is) in 2030. CONCLUSIONS:
      Considering developments over the past 24 years, it has been determined that the
      areas of the Chinese mainland that are experiencing the highest levels of growth
      in ageing populations are the two central provinces, which are connected to seven
      eastern provinces and five southwestern provinces. High ageing areas are not only
      concentrated in the eastern provinces, but also include Sichuan and Chongqing in
      the southwest region and Hubei and Hunan of the central region. The seven
      provinces (municipalities or autonomous regions) of the central and western
      regions have both high ageing levels and strong growth rates, but the growth rate
      is decreasing.

PMID- 29661175
TI  - Adherence to the Qatar dietary guidelines: a cross-sectional study of the gaps,
      determinants and association with cardiometabolic risk amongst adults.
AB  - BACKGROUND: The Qatar Dietary Guidelines (QDGs) were developed as part of the
      national strategy to prevent chronic diseases. This study aims at characterizing
      gaps between the QDGs and usual dietary and lifestyle patterns in Qatar,
      identifying demographic and socioeconomic determinants of adherence to the QDGs
      and investigating the association between adherence and cardiometabolic risk.
      METHODS: This study is based on the Qatar National STEPwise cross-sectional
      survey which was conducted on a nationally representative sample of Qatari
      adults, aged 18 to 64 years (n = 1109). Data collection included socio
      demographic characteristics, lifestyle factors, anthropometric (weight, height
      and waist circumference (WC)), and blood pressure measurements. The dietary
      intake of participants was evaluated using a non-quantitative food frequency
      questionnaire (FFQ). Biochemical assessment was performed to measure the fasting
      levels of blood sugar, triglycerides (TG) and HDL cholesterol. The metabolic
      syndrome (MetS) was defined as the presence of three or more cardiometabolic risk
      factors. To examine adherence to the guidelines, each specifc recommendation was
      matched to corresponding data drawn from the survey. To investigate the
      association of sociodemographic, lifestyle and cardiometabolic characteristics
      with adherence to the QDGs, an adherence score was calculated. RESULTS: More than
      83% of adults did not meet the recommendations for vegetables, fruits, whole
      grains, legumes and high fibre intakes, 70% were overweight or obese, 50-72%
      reported frequent consumption of sweetened beverages and sweets, and 47% reported
      frequent consumption of fast foods. Younger adults, the unemployed, the least
      educated and those not married had lower adherence to the QDGs. Adherence was
      inversely associated with elevated WC (OR: 0.88, 95% CI:0.82-0.95) and the MetS
      (OR:0.84,95% CI:0.74-0.96). CONCLUSIONS: Building on the identified gaps and
      vulnerable population groups, the study findings should provide a road map for
      the prioritization of interventions and the development of culture- specific
      programs aiming at promoting adherence to dietary guidelines in Qatar, while
      serving as a model to other countries in the region.

PMID- 29661177
TI  - Loss of ZG16 is associated with molecular and clinicopathological phenotypes of
      colorectal cancer.
AB  - BACKGROUND: Zymogen granule protein 16 (ZG16) is one of the most significantly
      down-regulated genes in colorectal cancer (CRC) tissues. This study aimed to
      further evaluate its expression changes and investigate its association with
      molecular and clinicopathological characteristics of CRC. METHODS: We applied
      quantitative RT-PCR to determine expression difference between tumor and matched
      normal tissues from 23 CRC patients. To further validate the down-regulation in
      tumor tissues, we performed immunohistochemistry (IHC) analysis in 40 paraffin
      embedded normal-tumor pairs and 22 colon tissues with a variety of diseases. To
      evaluate if the ZG16 gene changes were associated with clinicopathological
      characteristics, we further analyzed the gene expression and copy number changes
      from The Cancer Genome Atlas (TCGA) and Oncomine datasets. RESULTS: Quantitative
      RT-PCR confirmed significant down-regulation (~ 130-fold) of ZG16 in all tumor
      tissues. ZG16 expression was in an organ-specific manner with an extremely high
      expression in normal epithelial cells of small intestine, colon and rectum. IHC
      analysis showed that ZG16 protein was completely lost in all of 40 CRC tissues,
      and partially lost in premalignant adenomatous polyps (adenomas) and chronic
      ulcerative colitis tissues. Gene expression and copy number changes were
      significantly associated with multiple molecular and clinicopathological features
      of CRC including microsatellite instability (MSI), MLH1 silencing, CpG island
      methylator phenotype, hyper-mutation status, gender, presence of synchronous
      adenomas, and histological type (P < 0.05). Patients with lower ZG16 gene
      expression showed shorter progression-free survival and overall survival than
      those with relatively higher expression (P < 0.05). Multivariate analysis
      suggested that the ZG16 expression was an independent prognosis factor (P =
      0.012, HR = 6.286, 95% CI = 0.816-0.975). CONCLUSION: For the first time, our
      study demonstrated that ZG16 expression was sequentially reduced from normal,
      adenoma, to carcinoma. Association with multiple clinicopathological features
      indicates that ZG16 may play an important role in cancer initiation and
      progression. ZG16 may serve as a potential biomarker for diagnosis and prognosis
      of CRC.

PMID- 29661178
TI  - Mobile-health tool to improve maternal and neonatal health care in Bangladesh: a
      cluster randomized controlled trial.
AB  - BACKGROUND: In Bangladesh, the targets on reduction of maternal mortality and
      utilization of related obstetric services provided by skilled health personnel in
      Millennium Development Goals 5 remains unmet, and the progress in reduction of
      neonatal mortality lag behind that in the reduction of infant and under-five
      mortalities, remaining as an essential issue towards the achievement of maternal
      and neonatal health targets in health related Sustainable Development Goals
      (SDGs). As access to appropriate perinatal care is crucial to reduce maternal and
      neonatal deaths, recently several mobile platform-based health programs sponsored
      by donor countries and Non-Governmental Organizations have targeted to reduce
      maternal and child mortality. On the other hand, good health-care is necessary
      for the development. Thus, we designed this implementation research to improve
      maternal and child health care for targeting SDGs. METHODS/DESIGN: This cluster
      randomized trial will be conducted in Lohagora of Narail District and Dhamrai of
      Dhaka District. Participants are pregnant women in the respective areas. The
      total sample size is 3000 where 500 pregnant women will get Mother and Child
      Handbook (MCH) and messages using mobile phone on health care during pregnancy
      and antenatal care about one year in each area. The other 500 in each area will
      get health education using only MCH book. The rest 1000 participants will be
      controlled; it means 500 in each area. We randomly assigned the intervention and
      controlled area based on smallest administrative area (Unions) in Bangladesh. The
      data collection and health education will be provided through trained research
      officers starting from February 2017 to August 2018. Each health education
      session is conducting in their house. The study proposal was reviewed and
      approved by NCCD, Japan and Bangladesh Medical Research Council (BMRC),
      Bangladesh. The data will be analyzed using STATA and SPSS software. DISCUSSION:
      For the improvement of maternal and neonatal care, this community-based
      intervention using mobile phone and handbook will do great contribution. Thus, a
      developing country where resources are limited received the highest benefit. Such
      intervention will guide to design for prevention of other diseases too. TRIAL
      REGISTRATION: UMIN000025628 Registered June 13, 2016.

PMID- 29661179
TI  - Outcomes of pathologic stage T3a renal cell carcinoma up-staged from small renal
      tumor: emphasis on partial nephrectomy.
AB  - BACKGROUND: The prognosis of patients with pathologic stage T3a renal cell
      carcinoma (RCC) that is up-staged from a small renal tumor remains controversial.
      We evaluated the prognosis of patients with RCC who were up-staged from clinical
      stage T1 to pathologic stage T3a. METHODS: We retrospectively reviewed the data
      of 3431 patients who were surgically treated for clinical stage T1 RCC. The
      survival outcomes were compared using Kaplan-Meier and Cox proportional analyses.
      RESULTS: Among the clinical stage T1 patients, 215 (6.3%) were finally up-staged
      to pathologic stage T3a. Patient age (HR 1.302, 95% CI 1.018-1.046, p <  0.001),
      tumor diameter (HR 1.686, 95% CI 1.551-1.834, p <  0.001), and hilar location (HR
      1.765, 95% CI 1.147-2.715, p = 0.010) were significantly associated with
      upstaging. Kaplan-Meier analyses showed significantly shorter recurrence-free,
      cancer-specific and overall survivals (all p <  0.001) in patients who were up
      staged. Multivariate Cox analyses revealed pathologic upstaging as an independent
      predictor of shorter recurrence-free (HR 2.195, 95% CI 1.459-3.300, p <  0.001),
      cancer-specific (HR 2.238, 95% CI 1.252-4.003, p = 0.007), and overall survivals
      (HR 1.632, 95% CI 1.029-2.588, p = 0.037). Subgroup analysis of pathologic stage
      T3a showed no significant difference in survival of the partial nephrectomy group
      when compared to the radical nephrectomy group (all p > 0.5). CONCLUSIONS:
      Patients up-staged from clinical stage T1 to pathologic stage T3a RCC showed
      shorter survival outcomes than those without upstaging. However, partial
      nephrectomy, compared with radical nephrectomy, showed comparable outcomes in
      patients who were up-staged.

PMID- 29661180
TI  - Trends and correlates of unhealthy dieting behaviours among adolescents in the
      United States, 1999-2013.
AB  - BACKGROUND: The increase in adiposity problems among United States adolescents
      has been accompanied by persistently high prevalence of unhealthy dieting
      behaviours (UDBs) such as fasting, taking diet pills/powders/liquids, and
      vomiting/taking laxatives. This study aimed to examine the associations of self
      perceptions of weight status, weight change intentions (WCIs) and UDBs with sex,
      age and race, as well as trends of UDBs in American adolescents across the weight
      spectrum. METHODS: Data come from the biennial cross-sectional, school-based
      surveys, the Youth Risk Behaviour Surveillance System (1999-2013, n = 113,542).
      The outcome measures were the self-reported UDBs: fasting for 24 h or more;
      taking diet pills/powders/liquids; and vomiting/taking laxatives. Sex-stratified
      logistic regressions assessed relationships between weight status misperceptions
      across all weight statuses, race and WCIs with UDBs. Differential trends between
      races were assessed using race*year interaction terms. RESULTS: In males, all non
      White races had higher odds of fasting and vomiting/taking laxatives than Whites
      (except fasting in Hispanic/Latinos), with Adjusted Odds Ratios (AORs) between
      1.44 and 2.07. In females, Black/African Americans and Hispanic/Latinos had lower
      odds of taking diet pills/powders/liquids compared to Whites (AORs 0.50 and 0.78
      respectively). Racial disparities persisted throughout the study period.
      Prevalence of fasting and vomiting/taking laxatives did not change between 1999
      and 2013 for all races, while taking diet pills/powders/liquids decreased.
      Compared to individuals of normal weight who were accurate weight status
      perceivers, individuals of almost all other combinations of weight status and
      weight status perception had significantly higher odds of displaying any UDB
      outcome. Overestimation of weight status was found to be the strongest
      determinant of UDBs. Compared to individuals endorsing "not wanting to do
      anything" about their weight, individuals endorsing all other WCIs (including
      wanting to gain weight) also showed significantly higher odds for every UDB
      outcome, with wanting to lose weight having AORs of the greatest magnitudes.
      CONCLUSIONS: Prevalence of UDBs is persistently high, and highest among females
      across all racial groups. UDBs may elevate undesired weight gain and weight loss
      in individuals who are obese/overweight and underweight respectively. Further
      research into weight status perceptions among adolescents may inform efforts to
      reduce UDBs.

PMID- 29661181
TI  - TLR4 modulates inflammatory gene targets in the retina during Bacillus cereus
      endophthalmitis.
AB  - BACKGROUND: Endophthalmitis is a serious intraocular infection that frequently
      results in significant inflammation and vision loss. Because current therapeutics
      are often unsuccessful in mitigating damaging inflammation during
      endophthalmitis, more rational targets are needed. Toll-like receptors (TLRs)
      recognize specific motifs on invading pathogens and initiate the innate
      inflammatory response. We reported that TLR4 contributes to the robust
      inflammation which is a hallmark of Bacillus cereus endophthalmitis. To identify
      novel, targetable host inflammatory factors in this disease, we performed
      microarray analysis to detect TLR4-dependent changes to the retinal transcriptome
      during B. cereus endophthalmitis. RESULTS: C57BL/6 J and TLR4-/- mouse eyes were
      infected with B. cereus and retinas were harvested at 4 h postinfection, a time
      representing the earliest onset of neutrophil infiltration. Genes related to
      acute inflammation and inflammatory cell recruitment including CXCL1 (KC), CXCL2
      (MIP2-alpha), CXCL10 (IP-10), CCL2 (MCP1), and CCL3 (MIP1-alpha)) were
      significantly upregulated 5-fold or greater in C57BL/6 J retinas. The immune
      modulator IL-6, intercellular adhesion molecule ICAM1, and the inhibitor of
      cytokine signal transduction SOCS3 were upregulated 25-, 11-, and 10-fold,
      respectively, in these retinas. LIF, which is crucial for photoreceptor cell
      survival, was increased 6-fold. PTGS2/COX-2, which converts arachidonic acid to
      prostaglandin endoperoxide H2, was upregulated 9-fold. PTX3, typically produced
      in response to TLR engagement, was induced 15-fold. None of the aforementioned
      genes were upregulated in TLR4-/- retinas following B. cereus infection.
      CONCLUSIONS: Our results have identified a cohort of mediators driven by TLR4
      that may be important in regulating pro-inflammatory and protective pathways in
      the retina in response to B. cereus intraocular infection. This supports the
      prospect that blocking the activation of TLR-based pathways might serve as
      alternative targets for Gram-positive and Gram-negative endophthalmitis therapies
      in general.

PMID- 29661182
TI  - Women's perspectives on the ethical implications of non-invasive prenatal
      testing: a qualitative analysis to inform health policy decisions.
AB  - BACKGROUND: Non-Invasive Prenatal Testing (NIPT) is a technology which provides
      information about fetal genetic characteristics (including sex) very early in
      pregnancy by examining fetal DNA obtained from a sample of maternal blood. NIPT
      is a morally complex technology that has advanced quickly to market with a strong
      push from industry developers, leaving many areas of uncertainty still to be
      resolved, and creating a strong need for health policy that reflects women's
      social and ethical values. We approach the need for ethical policy-making by
      studying the use of NIPT and emerging policy in the province of Ontario, Canada.
      METHODS: Using an adapted version of constructivist grounded theory, we conducted
      interviews with 38 women who have had personal experiences with NIPT. We used an
      iterative process of data collection and analysis and a staged coding strategy to
      conduct a descriptive analysis of ethics issues identified implicitly and
      explicitly by women who have been affected by this technology. RESULTS: The
      findings of this paper focus on current ethical issues for women seeking NIPT,
      including place in the prenatal pathway, health care provider counselling about
      the test, industry influence on the diffusion of NIPT, consequences of
      availability of test results. Other issues gain relevance in the context of
      future policy decisions regarding NIPT, including funding of NIPT and principles
      that may govern the expansion of the scope of NIPT. These findings are not an
      exhaustive list of all the potential ethical issues related to NIPT, but rather a
      representation of the issues which concern women who have personal experience
      with this test. CONCLUSIONS: Women who have had personal experience with NIPT
      have concerns and priorities which sometimes contrast dramatically with the
      theoretical ethics literature. These findings suggest the importance of engaging
      patients in ethical deliberation about morally complex technologies, and point to
      the need for more deliberative patient engagement work in this area.

PMID- 29661183
TI  - Linguistic validation, validity and reliability of the British English versions
      of the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire and
      QuickDASH in people with rheumatoid arthritis.
AB  - BACKGROUND: Although the Disabilities of the Arm, Shoulder and Hand (DASH)
      questionnaire is widely used in the UK, no British English version is available.
      The aim of this study was to linguistically validate the DASH into British
      English and then test the reliability and validity of the British English DASH,
      (including the Work and Sport/Music DASH) and QuickDASH, in people with
      rheumatoid arthritis (RA). METHODS: The DASH was forward translated, reviewed by
      an expert panel and cognitive debriefing interviews undertaken with 31 people
      with RA. Content validity was evaluated using the ICF Core Set for RA.
      Participants with RA (n = 340) then completed the DASH, Health Assessment
      Questionnaire (HAQ), Short Form Health Survey v2 (SF36v2) and Measure of Activity
      Performance of the Hand (MAPHAND). We examined internal consistency and
      concurrent validity for the DASH, Work and Sport/Music DASH modules and
      QuickDASH. Participants repeated the DASH to assess test-retest reliability.
      RESULTS: Minor wording changes were made as required. The DASH addresses a
      quarter of Body Function and half of Activities and Participation codes in the
      ICF RA Core Set. Internal consistency for DASH scales were consistent with
      individual use (Cronbach's alpha = 0.94-0.98). Concurrent validity was strong
      with the HAQ (rs = 0.69-0.91), SF36v2 Physical Function (rs = - 0.71 - - 0.85),
      Bodily Pain (rs = - 0.71 - - 0.74) scales and MAPHAND (rs = 0.71-0.93). Test
      retest reliability was good (rs = 0.74-0.95). CONCLUSIONS: British English
      versions of the DASH, QuickDASH and Work and Sport/Music modules are now
      available to evaluate upper limb disabilities in the UK. The DASH, QuickDASH,
      Work and Sport/Music modules are reliable and valid to use in clinical practice
      and research with British people with RA.

PMID- 29661184
TI  - Genetic variants of SLC12A3 modulate serum lipid profiles in a group of Mongolian
      pedigree population.
AB  - BACKGROUND: The serum lipid profile, including LDL-C level, is associated with
      hypertension which is the major cause of cerebrovascular disease (CVD) amounting
      30% of global death rate. Previous work also demonstrated important roles of
      genetic variants of SLC12A3 gene on human CVD, hypertension and other diseases in
      Mongolian population. However, the relationship between SLC12A3 gene
      polymorphisms on individuals' lipid profile is still unknown. METHODS: A panel of
      15 SNPs of SLC12A3 gene was genotyped within a 424 Mongolians pedigree cohort.
      The associations between SLC12A3 polymorphisms and four lipid profiles were
      analyzed by family-based association test (FBAT) and confirmed with haplotype
      analysis. RESULTS: From both single site and haplotype analyses, the results
      demonstrated a close relationship between SLC12A3 polymorphisms and LDL-C level.
      Two SNPs, rs5803 and rs711746 showed significant associations with individuals'
      serum LDL-C level (z = - 2.08, P -e  = 0.038; z = 2.09, P -e  = 0.023,
      respectively), and distribution of haplotypes constructed by two SNPs also
      associated with participants' serum LDL-C level, significantly (Global Chi2 =
      9.06 df = 3, P = 0.028). CONCLUSION: Our results demonstrated the importance of
      SLC12A3 polymorphisms in individuals' difference about their serum lipid
      profiles, thereby providing evidence that the genetic variants may contribute to
      CVD development via modulating person's LDL-C level and blood pressure, in
      certain contexts.

PMID- 29661186
TI  - The positive role of vitronectin in radiation induced lung toxicity: the in vitro
      and in vivo mechanism study.
AB  - BACKGROUND: Radiation-induced lung toxicity (RILT) is a severe complication of
      radiotherapy in patients with thoracic tumors. Through proteomics, we have
      previously identified vitronectin (VTN) as a potential biomarker for patients
      with lung toxicity of grade >= 2 radiation. Herein, we explored the molecular
      mechanism of VTN in the process of RILT. METHODS: In this study, lentivirus
      encoding for VTN and VTN-specific siRNA were constructed and transfected into the
      cultured fibroblasts and C57BL mice. Real-time PCR, western blot and ELISA were
      used to examine expression of collagens and several potential proteins involved
      in lung fibrosis. Hematoxylin-eosin and immunohistochemical staining were used to
      assess the fibrosis scores of lung tissue from mice received irradiation.
      RESULTS: The expression of VTN was up-regulated by irradiation. The change trend
      of collagens, TGF-beta expression and p-ERK, p-AKT, and p-JNK expression levels
      were positively related with VTN mRNA level. Furthermore, overexpression of VTN
      significantly increased the expression level of alpha-SMA, as well as the degree
      of lung fibrosis in mice at 8 and 12 weeks post-irradiation. By contrast, siRNA
      VTN induced opposite results both in vitro and in vivo. CONCLUSIONS: VTN played a
      positive role in the lung fibrosis of RILT, possibly through modulation of
      fibrosis regulatory pathways and up-regulating the expression levels of fibrosis
      related genes. Taken together, all the results suggested that VTN had a novel
      therapeutic potential for the treatment of RILT.

PMID- 29661185
TI  - Madagascar ground gecko genome analysis characterizes asymmetric fates of
      duplicated genes.
AB  - BACKGROUND: Conventionally, comparison among amniotes - birds, mammals, and
      reptiles - has often been approached through analyses of mammals and, for
      comparison, birds. However, birds are morphologically and physiologically derived
      and, moreover, some parts of their genomes are recognized as difficult to
      sequence and/or assemble and are thus missing in genome assemblies. Therefore,
      sequencing the genomes of reptiles would aid comparative studies on amniotes by
      providing more comprehensive coverage to help understand the molecular mechanisms
      underpinning evolutionary changes. RESULTS: Herein, we present the whole genome
      sequences of the Madagascar ground gecko (Paroedura picta), a promising study
      system especially in developmental biology, and used it to identify changes in
      gene repertoire across amniotes. The genome-wide analysis of the Madagascar
      ground gecko allowed us to reconstruct a comprehensive set of gene phylogenies
      comprising 13,043 ortholog groups from diverse amniotes. Our study revealed 469
      genes retained by some reptiles but absent from available genome-wide sequence
      data of both mammals and birds. Importantly, these genes, herein collectively
      designated as 'elusive' genes, exhibited high nucleotide substitution rates and
      uneven intra-genomic distribution. Furthermore, the genomic regions flanking
      these elusive genes exhibited distinct characteristics that tended to be
      associated with increased gene density, repeat element density, and GC content.
      CONCLUSION: This highly continuous and nearly complete genome assembly of the
      Madagascar ground gecko will facilitate the use of this species as an
      experimental animal in diverse fields of biology. Gene repertoire comparisons
      across amniotes further demonstrated that the fate of a duplicated gene can be
      affected by the intrinsic properties of its genomic location, which can persist
      for hundreds of millions of years.

PMID- 29661188
TI  - Molecular and clinical analyses of Helicobacter pylori colonization in inflamed
      dental pulp.
AB  - BACKGROUND: Recently, dental pulp has been considered a possible source of
      infection of Helicobacter pylori (H. pylori) in children. We previously developed
      a novel PCR system for H. pylori detection with high specificity and sensitivity
      using primer sets constructed based on the complete genome information for 48 H.
      pylori strains. This PCR system showed high sensitivity with a detection limit of
      1-10 cells when serial dilutions of H. pylori genomic DNA were used as templates.
      However, the detection limit was lower (102-103 cells) when H. pylori bacterial
      DNA was detected from inflamed pulp specimens. Thus, we further refined the
      system using a nested PCR method, which was much more sensitive than the previous
      single PCR method. In addition, we examined the distribution and virulence of H.
      pylori in inflamed pulp tissue. METHODS: Nested PCR system was constructed using
      primer sets designed from the complete genome information of 48 H. pylori
      strains. The detection limit of the nested PCR system was 1-10 cells using both
      H. pylori genomic DNA and bacterial DNA isolated from inflamed pulp specimens.
      Next, distribution of H. pylori was examined using 131 inflamed pulp specimens
      with the nested PCR system. In addition, association between the detection of H.
      pylori and clinical information regarding endodontic-infected teeth were
      investigated. Furthermore, adhesion property of H. pylori strains to human dental
      fibroblast cells was examined. RESULTS: H. pylori was present in 38.9% of
      inflamed pulp specimens using the nested PCR system. H. pylori was shown to be
      predominantly detected in primary teeth rather than permanent teeth. In addition,
      samplings of the inflamed pulp were performed twice from the same teeth at 1- or
      2-week intervals, which revealed that H. pylori was detected in most specimens in
      both samplings. Furthermore, H. pylori strains showed adhesion property to human
      dental fibroblast cells. CONCLUSION: Our results suggest that H. pylori colonizes
      inflamed pulp in approximately 40% of all cases through adhesion to human dental
      fibroblast cells.

PMID- 29661187
TI  - Incidence and risk factors for recurrent Henoch-Schonlein purpura in children
      from a 16-year nationwide database.
AB  - BACKGROUND: The recurrence rate of Henoch-Schonlein purpura (HSP) is 2.7%-30%,
      with varied average intervals between the first and second episodes. Few studies
      have explored the incidence and risk factors for recurrent HSP. METHODS: We used
      a 16-year nationwide database to analyze the incidence of recurrent HSP. Patients
      with HSP were identified, and risk factors for recurrent HSP were explored.
      Kaplan-Meier and Cox regression model analyses were performed, and covariates
      were adjusted in the multivariate model. RESULTS: From January 1, 1997 to
      December 31, 2012, among 2,886,836 individuals in the National Health Insurance
      Research Database, 1002 HSP patients aged < 18 years were identified. Among them,
      164 had >=2 HSP episodes (recurrence rate, 16.4%; incidence of recurrent HSP,
      7.05 per 100 person-years); 83.6% patients with one HSP episode remained free of
      secondary HSP. The average time intervals between the first and second and second
      and third HSP episodes were 9.2 and 6.4 months, respectively. After adjusting for
      demographic parameters, comorbidities, and socioeconomic status, recurrent HSP
      was found to occur more frequently in patients who had renal involvement
      (adjusted hazard ratio, 2.41; 95% confidence interval [CI], 1.64-3.54; p <
      0.001), were receiving steroid therapy for > 10 days (adjusted hazard ratio,
      8.13; 95%CI, 2.51-26.36; p < 0.001), and had allergic rhinitis (adjusted hazard
      ratio, 1.63; 95%CI, 1.06-2.50; p = 0.026). CONCLUSIONS: The annual incidence of
      recurrent HSP was low. However, children who had underlying allergic rhinitis,
      presented with renal involvement, and received steroid treatment for > 10 days
      should be notified regarding the possibility of recurrence.

PMID- 29661189
TI  - Origins in the USA in the 1980s of the warning that smokeless tobacco is not a
      safe alternative to cigarettes: a historical, documents-based assessment with
      implications for comparative warnings on less harmful tobacco/nicotine products.
AB  - BACKGROUND: Before the 1980s in the USA, smokeless tobacco carried no health
      warnings, was not judged to cause disease, and was a declining practice. In 1986,
      the federal government passed legislation requiring rotating warnings on "mouth
      cancer," "gum disease and tooth loss," and "This product is not a safe
      alternative to cigarettes." This paper explores the history of the establishment
      of these warnings with emphasis on the 'not a safe alternative' warning and the
      bases for claiming that smokeless was 'not safe' (absolute harm) versus 'not
      safer than cigarettes' (relative harm). METHODS: Results of searches of Truth
      Tobacco Industry Document archives and transcripts of legislative hearings were
      analyzed. Critical assessments were made of the evidence-base. RESULTS: New
      evidence of oral cancer causation emerged along with a much-publicized case of a
      teenager dying of oral cancer. Public health concerns also arose over a
      widespread, successful marketing campaign implying smokeless was a safe
      alternative to cigarettes. Industry wanted pre-emptive federal warnings, to
      prevent a diversity of pending state warnings. To avoid an addiction warning, the
      industry accepted a compromise 'not a safe alternative' warning, which had not
      been initially proposed and which the cigarette industry may have sought in order
      to constrain the smokeless tobacco industry. The evidence presented supported
      smokeless only as 'not safe' and not 'as harmful as cigarette smoking.'
      CONCLUSIONS: The comparative warning was a compromise to prevent an addiction
      warning and consistent with the preferences of cigarette companies. Prior surveys
      indicated that the public generally did not view smokeless tobacco as harmless,
      but they did generally report smokeless as less harmful than cigarettes despite
      expert interpretations to the contrary. As would not have been appreciated by
      public health supporters at the outset, subsequent research has shown that the
      'not a safe alternative' message is misinterpreted by consumers to indicate that
      smokeless is 'not safer' than cigarettes-which was not established and has been
      disconfirmed by subsequent assessments of that question. Though many countries
      have banned smokeless tobacco (but not cigarettes), where smokeless is legally
      available accurate information on the nature of harms and differential harms
      needs to be developed.

PMID- 29661191
TI  - Factors associated with treatment-seeking for malaria in urban poor communities
      in Accra, Ghana.
AB  - BACKGROUND: In Ghana, about 3.5 million cases of malaria are recorded each year.
      Urban poor residents particularly have a higher risk of malaria mainly due to
      poor housing, low socio-economic status and poor sanitation. Alternative
      treatment for malaria (mainly African traditional/herbal and/or self-medication)
      is further compounding efforts to control the incidence of malaria in urban poor
      communities. This study assesses factors associated with seeking alternative
      treatment as the first response to malaria, relative to orthodox treatment in
      three urban poor communities in Accra, Ghana. METHODS: This cross-sectional study
      was conducted in three urban poor localities in Accra, Ghana among individuals in
      their reproductive ages (15-59 years for men and 15-49 years for women). The
      analytic sample for the study was 707. A multinomial regression model was used to
      assess individual, interpersonal and structural level factors associated with
      treatment-seeking for malaria. RESULTS: Overall, 31% of the respondents sought
      orthodox treatment, 8% sought traditional/herbal treatment and 61% self-medicated
      as the first response to malaria. At the bivariate level, more males than females
      used traditional/herbal treatment and self-medicated for malaria. The results of
      the regression analysis showed that current health insurance status, perceived
      relative economic standing, level of social support, and locality of residence
      were associated with seeking alternative treatment for malaria relative to
      orthodox treatment. CONCLUSIONS: The findings show that many urban poor residents
      in Accra self-medicate as the first response to malaria. Additionally,
      individuals who were not enrolled in a health insurance scheme, those who
      perceived they had a low economic standing, those with a high level of social
      support, and locality of residence were significantly associated with the use of
      alternative treatment for malaria. Multi-level strategies should be employed to
      address the use of alternative forms of treatment for malaria within the context
      of urban poverty.

PMID- 29661192
TI  - Policosanol composition, antioxidant and anti-arthritic activities of milk
      thistle (Silybium marianum L.) oil at different seed maturity stages.
AB  - BACKGROUND: Several anti-arthritic drugs and synthetic antioxidants have wide
      pharmaceutical uses and are often associated with various side effects on the
      human health. Dietary seed oils and their minor components like policosanol may
      offer an effective alternative treatment for arthritic and oxidative-stress
      related diseases. The biological effects of seed oils were affected by different
      parameters such as the stage of seed maturity. Hence, this study seeks to
      determine the policosanol content, antioxidant and anti-arthritic activities of
      milk thistle (Silybium marianum L.) oil extracted at various stages of seed
      maturation. METHODS: Milk thistle oil samples were extracted from seeds collected
      at three maturation stages (immature, intermediate, and mature). The 2,2-diphenyl
      1-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethyl-benzthiazoline-6-sulfonic
      acid) (ABTS) radical scavenging assays were used to determine the antioxidant
      activity of the extracted oils. The anti-arthritic activity of oil samples was
      evaluated with bovine serum protein denaturation and egg albumin denaturation
      methods. Gas chromatography coupled to mass spectrometry (GC-MS) was employed to
      determine the policosanol profile. RESULTS: Policosanol profile, antioxidant and
      anti-arthritic activities of milk thistle oil were influenced by the seed
      maturity stages. The oil extracted from the immature seeds had the highest total
      policosanol content (987.68 mg/kg of oil) and displayed the maximum antiradical
      activity (96.42% and 90.35% for DPPH test and ABTS assay, respectively). Nine
      aliphatic alcohols were identified in the milk thistle oil. The dominant
      poliosanol in the mature seed oil was octacosanol (75.44%), while triacontanol
      was the major compound (40.25%) in the immature seed oil. Additionally, the
      maximum inhibition of bovine serum protein denaturation (92.53%) and egg albumin
      denaturation (86.36%) were observed in immature seed oil as compared to mature
      seed oil. A high correlation was found between the total policosanol content,
      anti-arthritic activity and antioxidant capacity of oil. CONCLUSIONS: The milk
      thistle oil exhibited a potential anti-arthritic and antioxidant activities and
      that it might contribute to the protection of humans from a variety of diseases
      like rheumatoid arthritis. Also, it could serve as natural antioxidant and anti
      arthritic agents for application in the food industries and pharmaceutic.
      Policosanol level in the seed oils might contribute to their anti-arthritic and
      antioxidant activities.

PMID- 29661190
TI  - A manually annotated Actinidia chinensis var. chinensis (kiwifruit) genome
      highlights the challenges associated with draft genomes and gene prediction in
      plants.
AB  - BACKGROUND: Most published genome sequences are drafts, and most are dominated by
      computational gene prediction. Draft genomes typically incorporate considerable
      sequence data that are not assigned to chromosomes, and predicted genes without
      quality confidence measures. The current Actinidia chinensis (kiwifruit)
      'Hongyang' draft genome has 164 Mb of sequences unassigned to pseudo-chromosomes,
      and omissions have been identified in the gene models. RESULTS: A second genome
      of an A. chinensis (genotype Red5) was fully sequenced. This new sequence
      resulted in a 554.0 Mb assembly with all but 6 Mb assigned to pseudo-chromosomes.
      Pseudo-chromosomal comparisons showed a considerable number of translocation
      events have occurred following a whole genome duplication (WGD) event some
      consistent with centromeric Robertsonian-like translocations. RNA sequencing data
      from 12 tissues and ab initio analysis informed a genome-wide manual annotation,
      using the WebApollo tool. In total, 33,044 gene loci represented by 33,123
      isoforms were identified, named and tagged for quality of evidential support. Of
      these 3114 (9.4%) were identical to a protein within 'Hongyang' The Kiwifruit
      Information Resource (KIR v2). Some proportion of the differences will be
      varietal polymorphisms. However, as most computationally predicted Red5 models
      required manual re-annotation this proportion is expected to be small. The
      quality of the new gene models was tested by fully sequencing 550 cloned
      'Hort16A' cDNAs and comparing with the predicted protein models for Red5 and both
      the original 'Hongyang' assembly and the revised annotation from KIR v2. Only
      48.9% and 63.5% of the cDNAs had a match with 90% identity or better to the
      original and revised 'Hongyang' annotation, respectively, compared with 90.9% to
      the Red5 models. CONCLUSIONS: Our study highlights the need to take a cautious
      approach to draft genomes and computationally predicted genes. Our use of the
      manual annotation tool WebApollo facilitated manual checking and correction of
      gene models enabling improvement of computational prediction. This utility was
      especially relevant for certain types of gene families such as the EXPANSIN like
      genes. Finally, this high quality gene set will supply the kiwifruit and general
      plant community with a new tool for genomics and other comparative analysis.

PMID- 29661193
TI  - Simulation of phase contrast angiography for renal arterial models.
AB  - BACKGROUND: With the development of versatile magnetic resonance acquisition
      techniques there arises a need for more advanced imaging simulation tools to
      enable adequate image appearance prediction, measurement sequence design and
      testing thereof. Recently, there is a growing interest in phase contrast
      angiography (PCA) sequence due to the capabilities of blood flow quantification
      that it offers. Moreover, as it is a non-contrast enhanced protocol, it has
      become an attractive option in areas, where usage of invasive contrast agents is
      not indifferent for the imaged tissue. Monitoring of the kidney function is an
      example of such an application. RESULTS: We present a computer framework for
      simulation of the PCA protocol, both conventional and accelerated with echo
      planar imaging (EPI) readout, and its application to the numerical models of
      kidney vasculatures. Eight patient-specific renal arterial trees were
      reconstructed following vessel segmentation in real computed tomography
      angiograms. In addition, a synthetic model was designed using a vascular tree
      growth simulation algorithm. The results embrace a series of synthetic PCA images
      of the renal arterial trees giving insight into the image formation and
      quantification of kidney hemodynamics. CONCLUSIONS: The designed simulation
      framework enables quantification of the PCA measurement error in relation to
      ground-truth flow velocity data. The mean velocity measurement error for the
      reconstructed renal arterial trees range from 1.5 to 12.8% of the aliasing
      velocity value, depending on image resolution and flip angle. No statistically
      significant difference was observed between measurements obtained using EPI with
      a number of echos (NETL) = 4 and conventional PCA. In case of higher NETL factors
      peak velocity values can be underestimated up to 34%.

PMID- 29661194
TI  - Association of neighborhood greenness with self-perceived stress, depression and
      anxiety symptoms in older U.S adults.
AB  - BACKGROUND: Neighborhood environment, such as green vegetation, has been shown to
      play a role in coping with stress and mental ill health. Yet, epidemiological
      evidence of the association between greenness and mental health is inconsistent.
      METHODS: We examined whether living in green space is associated with self
      perceived stress, depressive and anxiety symptoms in a nationally representative,
      longitudinal sample of community-dwelling older adults (N = 4118; aged 57-85
      years) in the United States. We evaluated perceived stress, depression and
      anxiety symptoms using the Cohen's Perceived Stress Scale, the Center for
      Epidemiological Studies - Depression, and the Hospital Anxiety and Depression
      Scale - anxiety subscale, respectively. Greenness was assessed for each
      participant using the Normalized Difference Vegetation Index at 250-m resolution,
      as well as a buffer of 1000-m. We conducted longitudinal analyses to assess the
      associations between greenness and mental health upon adjusting for confounders
      (e.g., education), and to examine potential mediation and effect modification.
      RESULTS: An interquartile range (0.25 point) increase in contemporaneous
      greenness was significantly associated with 0.238 unit (95% CI: - 0.346, - 0.130)
      and 0.162 unit (95% CI: - 0.271, - 0.054) decrease in the perceived stress in
      base and multivariable models, respectively. The magnitude of the association was
      similar or even stronger when examining summer (- 0.161; 95% CI: - 0.295, -
      0.027) and annual average of greenness (- 0.188; 95% CI: - 0.337, - 0.038), as
      well as greenness buffer of 1000-m. The greenness-stress association was
      partially mediated by physical activity (15.1% mediated), where increased
      greenness led to increased physical activity and less stress, and by history of
      respiratory diseases (- 3.8% mediated), where increased greenness led to
      increased respiratory disease and more stress. The association was also
      significantly modified by race, social support, physical function, socioeconomic
      status, and region. While greenness was not significantly associated with anxiety
      and depressive scores across all participants, significant inverse associations
      were found for Whites participants, and for individuals with higher socioeconomic
      status, who were physically active, as compared to their counterparts.
      CONCLUSION: We found a direct association of greenness with perceived stress
      among older adults, and an indirect association mediated through physical
      activity and respiratory disease history. Our study findings warrant further
      examination of the mediation and modification of the greenness-mental health
      association.

PMID- 29661195
TI  - Impact of patient involvement on clinical practice guideline development: a
      parallel group study.
AB  - BACKGROUND: Patient and public involvement (PPI) is recognized as a key component
      of clinical practice guideline development with important implications for
      guideline implementability. The impact of PPI on guidelines, however, has not
      been rigorously assessed. Better understanding of the impact of PPI must start
      with guideline question formation, which drives all subsequent development steps.
      The aim of this study was to investigate the effect of PPI on guideline question
      formation and validate a conceptual model of patient and public contributions to
      guidelines. METHODS: For development of a clinical practice guideline on the
      topic of using amyloid positron emission tomography in the diagnosis of dementia,
      we convened two parallel guideline development groups, one with and one without
      patient representatives. Participating physicians were randomized to group
      assignment. Each group developed Population, Intervention, Comparator, Outcome,
      Time (PICOT) questions and identified key benefits and harms to incorporate in
      guideline development. Analysis included a descriptive comparison of proposed
      PICOT questions, benefits, and harms between groups and a qualitative analysis of
      discussion themes from audio recordings of the question development retreats.
      RESULTS: Proposed guideline questions, benefits, and harms were largely similar
      between groups, but only the experimental group proposed outcomes relating to
      development of cognitive impairment at specific time points and rate of
      progression. The qualitative analysis of the discussions occurring during
      guideline question development demonstrated key differences in group conduct and
      validated the proposed conceptual model of patient and public contributions to
      guidelines. PPI influenced the conduct of guideline development, scope, inclusion
      of patient-relevant topics, outcome selection, and planned approaches to
      recommendation development, implementation, and dissemination with implications
      for both guideline developers and the guideline development process. CONCLUSIONS:
      Evidence of how PPI impacts guideline development underscores the importance of
      engaging patient stakeholders in guideline development and highlights developer-
      and guideline-specific outcomes of PPI, both of which have implications for
      guideline implementation. It also raises the question of whether guidelines
      developed without such input are acceptable for use. PPI should be considered an
      essential element of trustworthy guideline development for purposes of
      development and funding.

PMID- 29661196
TI  - The women's heart health programme: a pilot trial of sex-specific cardiovascular
      management.
AB  - BACKGROUND: There is increasing knowledge of sex-specific differences in
      cardiovascular disease and recognition of sex disparities in management. In our
      study, we investigated whether a cardiovascular programme tailored to the
      specific needs of women could lead to improved outcomes. METHODS: We randomised
      100 female patients to receive cardiology follow-up with the conventional sex
      neutral cardiac programme (control), or the sex-tailored Women's Heart Health
      Programme (intervention). The intervention group was managed by an all-women
      multidisciplinary team and received culture-centred health intervention
      workshops, designed through in-depth interviews with the participants. The
      primary outcome was cardiovascular risk factor improvement at 1 year. Secondary
      outcomes include cardiovascular event rates, quality of life scores, and self
      reported improvement in knowledge, attitudes, intentions and practices.
      Generalised structural equation model analysis was used to determine if the
      intervention group had better outcomes at alpha level 0.1. RESULTS: The mean age
      was 67.3 +/- 12.7 years, with an ethnic distribution of 70% Chinese, 18% Malays,
      and 12% Indians. The majority of these patients had no formal or primary level of
      education (63%), and were mostly unemployed (78%). Patients in intervention group
      had better control of diabetes mellitus (lower HbA1c of 0.63% [CI 0.21-1.04], p =
      0.015) and lower body-mass-index (0.74 kg/m2 [CI 0.02-1.46], p = 0.092) at 1
      year, but there was no significant difference in blood pressure or lipid control.
      Overall, there was a trend towards better risk factor control, 31.6% of
      intervention group versus 26.5% of control group achieved improvement in at least
      1 CV risk factor control to target range. There was no significant difference in
      incidence of cardiovascular events, quality of life, or domains in knowledge,
      attitudes, intention and practices. CONCLUSION: This pilot study is the first of
      its kind evaluating a new model of care for women with heart disease. The
      potential to improve outcomes needs to be studied in a larger trial with longer
      follow up. TRIAL REGISTRATION: This trial was prospectively registered
      clinicaltrials.gov on 6 May 2013. Trial Number: 2013/00088. Identifier:
      NCT02017470.

PMID- 29661197
TI  - Relevance and acceptability of using the Quantiferon gold test (QGIT) to screen
      CD4 blood draws for latent TB infection among PLHIV in South Africa: formative
      qualitative research findings from the TEKO trial.
AB  - BACKGROUND: Tuberculosis (TB) is the leading cause of mortality among people
      living with HIV (PLHIV), despite the availability of effective preventive
      therapy. The TEKO trial is assessing the impact of using a blood test,
      Quantiferon-TB Gold In-Tube Test (QGIT), to screen for latent TB compared to the
      Tuberculin Screening Test (TST) among PLHIV in South Africa. METHODS: Fifty-six
      qualitative interviews were conducted with PLHIV and clinical providers
      participating in the TEKO trial. We explored TB screening, diagnosis, and
      treatment guidelines and processes and the use of the QGIT to screen for latent
      TB infection at the time of CD4 blood draw. Thematic content analysis was
      conducted. RESULTS: Considerable variability in TB screening procedures was
      documented due to lack of personnel and clarity regarding current national TB
      guidelines for PLHIV. Few clinics had started using the TST per national
      guidelines and many patients had never heard of isoniazid preventive therapy
      (IPT). Nearly all participants supported the idea of latent TB screening using
      routine blood drawn for CD4 counts. CONCLUSIONS: Findings indicate that screening
      for latent TB infection using QGIT from blood drawn for CD4 counts among PLHIV is
      an acceptable approach to increase latent TB detection given the challenges
      associated with ensuring systematic latent TB screening in overburdened public
      clinics. TRIAL REGISTRATION: The results presented here were from formative
      research related to the TEKO trial (Identifier NCT02119130 , registered 10 April
      2014).

PMID- 29661198
TI  - Adverse effects of maternal enterovirus infection on the pregnancy outcome: a
      prospective and retrospective pilot study.
AB  - BACKGROUND: Enteroviruses account for about one billion infections worldwide each
      year, the majority remain asymptomatic. Data on enterovirus infections during
      pregnancy appear to be very rare. Several cases have been reported in the
      literature of fetal and neonatal complications attributed to these viruses, but
      prospective data on these infections during pregnancy are not available.
      OBJECTIVE: To estimate the prevalence of enterovirus infections in febrile
      syndromes in pregnant women, and in case of in utero fetal death (IUFD). METHODS:
      Ttri-centric observational cohort study. We performed prospective inclusion for
      patients with fever during a four-month period. We also analyzed the amniotic
      fluid in patients with unexplained IUFD retrospectively during a five-year
      period. Investigations of enteroviruses are made by RT-PCR from routine
      biological samples (amniocentesis, RT-PCR in maternal blood or CSF). RESULTS:
      Prospectively, 33 patients were included during the study period. We have
      identified 4 cases of confirmed enterovirus infection (12.4%). We have recorded a
      severe form of perinatal enterovirus infection involving the vital prognosis of
      the newborn. In the retrospective cohort of 75 IUFD cases, we had only one case
      of enterovirus-positive RT-PCR in amniotic fluid during 5 years, meaning a
      frequency of 1.3%. We did not had any positive EV case in case of early
      miscarriage, but the limited number of inclusions cannot help us to conclude.
      CONCLUSION: Enteroviruses are probably an underestimated cause of obstetric and
      neonatal complications. Investigation of enterovirus by PCR should be discussed
      during pregnancy and peripartum in case of febrile syndrome with no obvious
      bacterial cause, and unexplained IUFD.

PMID- 29661199
TI  - Adverse pregnancy outcomes in adolescents and young women with systemic lupus
      erythematosus: a national estimate.
AB  - BACKGROUND: Pregnant women with systemic lupus erythematosus (SLE) have increased
      risk of adverse outcomes including disease flare, spontaneous abortion,
      preeclampsia/eclampsia, premature birth and maternal death. However, pregnancy
      outcomes among adolescents and young women with SLE have not been well-explored.
      Our objective was to compare risk of adverse pregnancy outcomes in adolescents
      and young women with SLE to risk among peers without SLE. METHODS: We studied the
      2000-2011 Nationwide Inpatient Sample (NIS) of the Healthcare Cost and
      Utilization Project (HCUP) to estimate the prevalence of adverse pregnancy
      outcomes in women with SLE aged <= 21 years at time of delivery. Outcomes were
      compared to peers without SLE by using multivariate logistic regression to
      calculate odds ratios and risk differences. Additionally, differences in length
      of stay and total charges per hospitalization were described. RESULTS: There were
      8,791,391 unique pregnancies, of which 4002 occurred in young women with SLE.
      After adjustment for age, race, insurance type and quartile of median income
      based on patient ZIP code individuals with SLE had increased odds of pre
      eclampsia/eclampsia (OR 3.2, 95% CI 2.3-4.6), maternal death (OR 80, 95% CI 10
      604), preterm birth (OR 2.7, 95% CI 2-3.7), spontaneous abortion (OR 5.1, 95% CI
      2.8-9.6), and induced abortion (OR 30, 95% CI 14-63). The increase in risk among
      women with SLE was greatest for preterm birth (RD 11%, 95% CI 6-16), pre
      eclampsia/eclampsia (RD 9%, 95% CI 5-13), and spontaneous abortion (RD 4%, 95% CI
      0.9-6). Risk difference for induced abortion was 2% with 95% CI 0.6-4, while the
      difference in risk for maternal death did not reach statistical significance (RD
      0.4, 95% CI -0.4-1). CONCLUSIONS: Adolescents and young women with SLE experience
      increased risk of adverse, pregnancy-specific outcomes as compared to their
      peers, including pre-eclampsia/eclampsia, maternal death, preterm birth,
      spontaneous abortion, and induced abortion. Additionally, length of stay and
      total charges for hospitalization are increased.

PMID- 29661200
TI  - Application of the automated haematology analyzer XN-30 in an experimental rodent
      model of malaria.
AB  - BACKGROUND: The erythrocytic stage, where malaria parasites proliferate in human
      blood, is clinically significant as this causes the symptoms and illness of
      malaria. Experimental rodent models of malaria at the erythrocytic stage are used
      for the development of anti-malarial drugs and for biological analysis. An
      automated haematology analyzer XN-30 was developed for detection of infected red
      blood cells (iRBCs) in human blood samples and measurement of their parasitaemia
      in approximately 1 min through flow cytometry analysis. Additionally, the
      analyzer simultaneously measured other haematological parameters in these
      samples. It is inferred that the analyzer would also allow easy and rapid
      measurement of parasitaemia in mice and provide important clues on the mouse
      haematological state during infection and treatment. RESULTS: The XN-30 analyzer
      is a simple and rapid tool to detect iRBCs in mouse blood samples infected with
      rodent malarial parasites, with three-dimensional analysis permitting the precise
      measurement of parasitaemia (referred herein as the 'XN-30 system'). The XN-30
      analyzer allowed not only the detection of iRBCs but also the monitoring of RBC,
      white blood cell, and platelet counts, as well as haematocrit, mean corpuscular
      volume and mean platelet volume values in the mouse blood sample. For anti
      malarial drug development, aside from demonstrating possible efficacy in mouse
      models, XN-30 analyzer could provide a first glimpse of the safety profile of the
      drug. CONCLUSIONS: The XN-30 system is a powerful tool that can be utilized for
      the in vivo screening, development, and evaluation of anti-malarial drugs as well
      as for pre-clinical pharmacology and/or toxicity tests in rodent models.

PMID- 29661201
TI  - Feasibility of portal or superior mesenteric vein resection and reconstruction by
      allogeneic vein for pancreatic head cancer-a case-control study.
AB  - BACKGROUND: There are few reports about resection of portal vein (PV)/superior
      mesenteric vein (SMV) and reconstruction by using allogeneic vein. This case
      control study was designed to explore the feasibility and safety of this
      operation type in patients with T3 stage pancreatic head cancer. METHODS: A total
      of 42 patients (Group A) underwent PV/SMV resection and reconstruction by using
      allogeneic vein were 1:1 matched to 42 controls (Group B) with other types of
      resection and reconstruction. The two groups were well matched. RESULTS: There
      was no significantly prolonged total operation time (Group A vs. Group B [490.0
      min vs. 470 min], P = 0.067) and increased intraoperative blood loss (Group A vs.
      Group B [650.0 min vs. 450 min], P = 0.108) was found between the two groups. R1
      rate of PV/SMV was slightly reduced in group A compared to group B (4.8% vs.
      14.3%, P = 0.137), although no significant difference was found. The incidences
      of main postoperative complications between the two groups were similar. A
      slightly increased 1-year and 2-year overall survival rate (OS) (Group A vs.
      Group B [1-year OS: 62.9% vs. 57.0%; 2-year OS: 31.5% vs. 25.6%], P = 0.501) and
      disease-free survival rate (DFS) (Group A vs. Group B [1-year DFS: 43.9% vs.
      36.6%; 2-year DFS: 10.5% vs. 7.4%], P = 0.502) could be found in group A compared
      to group B, although the differences were not significant. CONCLUSIONS: The
      operation types of PV/SMV resection and reconstruction by using allogeneic vein
      is safety and feasible, it might have a potential benefit for patients.

PMID- 29661202
TI  - Exercise training improves intramuscular triglyceride lipolysis sensitivity in
      high-fat diet induced obese mice.
AB  - BACKGROUND: The purpose of this study was to determine whether regular exercise
      training enhances intramuscular triglyceride (IMTG) lipolysis sensitivity during
      consumption of a continued high-fat diet by exploring changes in biochemical
      factors activated by IMTG lipolysis. METHODS: Male C57BL/6 mice aged 4 weeks were
      randomly divided into a high-fat diet group (HF) to induce obesity for 6 weeks
      and a control (CO) group. Thereafter, the HF group was divided into a high-fat
      diet group (HF) and high-fat diet + training group (HFT). The HFT group was
      trained on an animal treadmill 40 min/day, 5 days/week for 8 weeks. PKA, Plin5, p
      Plin5, CGI-58, ATGL, and HSL were analyzed to investigate IMTG sensitivity by
      western blotting. RESULTS: PKA, CGI-58, and HSL protein levels in the HF group
      were significantly lower than those in the CO group (p < 0.05). However, PKA, CGI
      58, and HSL protein levels in the HFT group were significantly higher than those
      in the HF group, and ATGL and p-Plin5 protein levels as well as the p-Plin5/Plin5
      ratio in the HFT group were significantly higher than those in the HF group (p <
      0.05). In addition, the HF group showed a significantly higher IMTG volume than
      the CO and HFT groups (p < 0.05). CONCLUSIONS: These results suggest that in an
      obese mouse model, 8 weeks of treadmill exercise contributes to decreased IMTG
      volume by activating lipolysis factors, such as PKA, PLIN5, CGI-58, and lipases.
      Therefore, regular exercise training may play an important role in obesity
      treatment by increasing IMTG lipolysis sensitivity.

PMID- 29661203
TI  - Exploratory field study on the effect of Porcine circovirus 2 (PCV2) sow
      vaccination on serological, virological and reproductive parameters in a PCV2
      subclinically infected sow herd.
AB  - BACKGROUND: This study sought to evaluate the effect of sow vaccination against
      Porcine circovirus 2 (PCV2) on reproductive parameters during two consecutive
      reproductive cycles. The study was performed in a PCV2 subclinical infected
      breeding herd (PCV2 circulation but absence of major reproductive problems).
      Ninety-four pregnant sows were primo-immunized with a commercial PCV2 vaccine and
      ninety-seven were injected with phosphate-buffered saline at 6 and 3 weeks before
      the first studied farrowing, and then boosted at 2 weeks before the second one.
      Blood samples were taken throughout the study to assess PCV2 DNA load and
      antibodies. At farrowing, main reproductive parameters and piglet vitality index
      were registered. In addition, in those litters with more than three mummified or
      stillborn piglets, microscopic examination and PCV2 antigen detection in foetal
      myocardium was done. RESULTS: Vaccinated sows showed significantly higher
      antibody levels compared to the non-vaccinated counterparts. PCV2 DNA was only
      detected at farrowing in 2 (4.2%) non-vaccinated sows. Vaccinated sows had 1.3
      more live-born piglets per litter at the second cycle than non-vaccinated
      counterparts. Piglets from vaccinated sows had significantly higher (+ 12.7%)
      vitality score than the ones born from non-vaccinated sows. No PCV2 compatible
      lesions neither PCV2 antigen were detected in the tested foetal hearts.
      CONCLUSIONS: The present study represents a first attempt to demonstrate that
      PCV2 sow vaccination may have a positive influence on prolificacy and vitality of
      the offspring in a subclinical infected breeding herd. However, since
      reproductive outcomes at farm level may be affected by a number of factors,
      further studies would be needed to confirm this association.

PMID- 29661204
TI  - Surgical treatment outcomes of patients with T1-T2 gastric cancer: does the age
      matter when excellent treatment results are expected?
AB  - BACKGROUND: The proportion of early gastric cancer stages is increasing, as is
      the incidence of gastric cancer among the elderly population. Therefore, this
      study was designed to analyze surgical treatment outcomes of T1-T2 gastric cancer
      in elderly patients. METHODS: A total of 457 patients with T1-T2 gastric cancer
      who underwent gastrectomy between 2005 and 2015 were enrolled in this
      retrospective study. Patients were classified into two groups according to age (<
      70 years versus >= 70 years). Clinicopathological features, surgical treatment
      results, and clinical outcomes were compared between the groups. RESULTS: Higher
      ASA score (ASA 3/4), differentiated cancer, and intestinal-type tumors were more
      common in elderly patients. Postoperative complication rates were similar between
      the two groups; however, postoperative mortality rates were significantly higher
      in the elderly group. Higher ASA score was independently associated with
      postoperative complications in the elderly group. Furthermore, severe
      postoperative complications were found as an independent factor associated with
      higher 90-day mortality rate. Elderly patients had a significantly poorer 5-year
      overall survival rate. Two surgery-related factors-total gastrectomy and
      complicated postoperative course-were revealed as independent prognostic factors
      for poor overall survival in the elderly group. CONCLUSIONS: Despite higher
      postoperative mortality rate and poorer overall survival results, elderly
      patients with gastric cancer should be considered for radical surgery. ASA score
      may be useful for predicting surgical treatment outcomes in elderly patients
      undergoing surgery for GC and hence assists clinicians in planning treatment
      strategies for each individual patient.

PMID- 29661205
TI  - Comparison between minimally invasive spine stabilization with and without
      posterior decompression for the management of spinal metastases: a retrospective
      cohort study.
AB  - BACKGROUND: Posterior decompression and stabilization plays significant roles in
      palliative surgery for metastatic spinal tumor. However, the indication for
      addition of posterior decompression have not been examined. The purpose of this
      study was to investigate a retrospective cohort of outcomes of metastatic spinal
      tumor treated with minimally invasive spine stabilization (MISt) with or without
      posterior decompression. METHODS: The subjects were 40 patients who underwent
      MISt using percutaneous pedicle screws for metastatic spinal tumor, including 20
      patients treated with stabilization alone (group A) and 20 patients with added
      posterior decompression (group B). We analyzed baseline characteristics,
      postoperative survival time, and perioperative factors such as neurological
      outcomes, Barthel Index, VAS, and rate of discharge to home. RESULTS: The mean
      ages were 70 and 66 years old (P = 0.06), the mean revised Tokuhashi scores were
      7.2 and 5.8 (P = 0.1), the mean spinal instability neoplastic scores (SINS) were
      10.5 and 9.0 (P = 0.04), and the mean Barthel Index for ADL were 65.5 and 41.0 (P
      = 0.06) in groups A and B, respectively. The median postoperative survival time
      did not differ significantly between groups A and B (12.0 vs. 6.0 months, P =
      0.09). Patients in group A had a significantly shorter operation time (166 vs.
      232 min, P = 0.004) and lower intraoperative blood loss (120 vs. 478 mL, P <
      0.001). Postoperative paralysis (P = 0.1), paralysis improvement rate (P = 0.09),
      postoperative Barthel Index (P = 0.06), and postoperative VAS (P = 0.6) did not
      differ significantly between the groups. The modified Frankel classification
      improved from D1 or D2 before surgery to D3 or E after surgery in 4 of 10 cases
      (40%) in group A and 8 of 8 patients (100%) in group B (P = 0.01). Significantly
      more patients were discharged to home in group A (P = 0.02), whereas
      significantly more patients died in the hospital in group B (P = 0.02).
      CONCLUSIONS: Patients treated without decompression had a shorter operation time,
      less blood loss, a higher rate of discharge to home, and lower in-hospital
      mortality, indicating a procedure with lower invasiveness. MISt without
      decompression is advantageous for patients with D3 or milder paralysis, but
      decompression is necessary for patients with D2 or severer paralysis.

PMID- 29661206
TI  - Homology modelling, molecular docking, and molecular dynamics simulations reveal
      the inhibition of Leishmania donovani dihydrofolate reductase-thymidylate
      synthase enzyme by Withaferin-A.
AB  - OBJECTIVE: Present in silico study was carried out to explore the mode of
      inhibition of Leishmania donovani dihydrofolate reductase-thymidylate synthase
      (Ld DHFR-TS) enzyme by Withaferin-A, a withanolide isolated from Withania
      somnifera. Withaferin-A (WA) is known for its profound multifaceted properties,
      but its antileishmanial activity is not well understood. The parasite's DHFR-TS
      enzyme is diverse from its mammalian host and could be a potential drug target in
      parasites. RESULTS: A 3D model of Ld DHFR-TS enzyme was built and verified using
      Ramachandran plot and SAVES tools. The protein was docked with WA-the ligand,
      methotrexate (MTX)-competitive inhibitor of DHFR, and dihydrofolic acid (DHFA)
      substrate for DHFR-TS. Molecular docking studies reveal that WA competes for
      active sites of both Hu DHFR and TS enzymes whereas it binds to a site other than
      active site in Ld DHFR-TS. Moreover, Lys 173 residue of DHFR-TS forms a H-bond
      with WA and has higher binding affinity to Ld DHFR-TS than Hu DHFR and Hu TS. The
      MD simulations confirmed the H-bonding interactions were stable. The binding
      energies of WA with Ld DHFR-TS were calculated using MM-PBSA. Homology modelling,
      molecular docking and MD simulations of Ld DHFR-TS revealed that WA could be a
      potential anti-leishmanial drug.

PMID- 29661207
TI  - Repellent efficacy of a new combination of fipronil and permethrin against
      Lutzomyia longipalpis.
AB  - BACKGROUND: Lutzomyia longipalpis is the main vector of Leishmania infantum, the
      agent of canine and human visceral leishmaniosis in the Americas. Considering
      that the dog is the main domestic host of the parasite, repellent treatment is a
      measure that might contribute to the prevention of canine visceral leishmaniosis.
      The repellent efficacy of a single treatment of a new spot-on topical combination
      of fipronil and permethrin (Frontline Tri-Act(r), Merial, now part of Boehringer
      Ingelheim) to repel Lu. longipalpis sand flies was evaluated. METHODS: Sixteen
      healthy Beagle dogs, eight females and eight males, weighing 8.4-14.4 kg, and 2
      to 4 years-old were included in the study. Animals were blocked on decreasing
      body weight and randomly allocated within the blocks to one of two treatment
      groups of eight animals each. Dogs in Group 1 were untreated and Dogs in Group 2
      were treated with a combination containing 67.6 mg/ml fipronil + 504.8 mg/ml
      permethrin (Frontline Tri-Act(r)) once on Day 0. Sand fly exposures were
      performed on Days 1, 14, 21 and 30 with Lu. longipalpis female sand flies. After
      65 (+/- 15 min), sand flies were assessed for engorgement status. RESULTS: The
      percent repellency of the treated group compared to the untreated control group
      was 95.7, 94.3, 81.7 and 72.2% for exposure days 1, 14, 21 and 30, respectively.
      The two treatment groups were significantly different for all exposure days (P <=
      0.016 for days 1, 14, 21 and 30). No adverse reactions were observed during the
      study. CONCLUSION: A single topical administration of a new combination of
      fipronil and permethrin demonstrated a significant repellent effect against Lu.
      longipalpis bites as soon as it was applied on the dogs and its repellent
      efficacy lasted for 4 weeks with results greater than 80% for 3 weeks. The
      results suggest that in endemic areas the regular application of the new
      combination could contribute to protect dogs from Leishmania infection and
      therefore serve as an additional tool for the prevention of canine visceral
      leishmaniosis.

PMID- 29661208
TI  - Unmanipulated haploidentical in comparison with matched unrelated donor stem cell
      transplantation in patients 60 years and older with acute myeloid leukemia: a
      comparative study on behalf of the ALWP of the EBMT.
AB  - BACKGROUND: Acute myeloid leukemia (AML) is both more common and with more
      biologically aggressive phenotype in the elderly. Allogenic stem cell
      transplantation (allo-SCT) is the best treatment option in fit patients. Either
      HLA-matched unrelated donor (MUD) or haploidentical (Haplo) donor are possible
      alternative for patients in need. METHODS: We retrospectively compared non-T-cell
      depleted Haplo (n = 250) to 10/10 MUD (n = 2589) in AML patients >= 60 years.
      RESULTS: Median follow-up was 23 months. Disease status at transplant differs
      significantly between the two groups (p < 10-4). Reduced intensity conditioning
      (RIC) was administrated to 73 and 77% of Haplo and MUD, respectively (p = 0.23).
      Stem cell source was the bone marrow (BM) in 52% of the Haplo and 6% of MUD (p <
      10-4). Anti-thymocyte globulin (ATG) was most frequently used in MUD (p < 10-4)
      while post-Tx cyclophosphamide (PT-Cy) was given in 62% of Haplo. Engraftment was
      achieved in 90% of the Haplo vs 97% of MUD (p < 10-4). In multivariate analysis,
      no significant difference was found between Haplo and MUD for acute (a)graft
      versus host disease (GVHD) grade II-IV, relapse incidence (RI), non-relapse
      mortality (NRM), leukemia free survival (LFS), graft-versus-host-free-relapse
      free survival (GRFS), and overall survival (OS). Extensive chronic (c)GVHD was
      significantly higher for MUD as compared to Haplo (HR 2, p = 0.01, 95% CI 1.17
      3.47). A propensity score analysis confirmed the higher risk of extensive cGVHD
      for MUD without differences for other outcomes. CONCLUSIONS: Allo-SCT from both
      Haplo and MUD are valid option for AML patients >= 60 years of age with similar
      results. Transplantation from MUD was associated with higher extensive cGVHD. Our
      findings suggest that Haplo is a suitable and attractive graft source for
      patients>= 60 with AML in need of allo-SCT.

PMID- 29661209
TI  - Gastrointestinal and urinary complaints in adults with hereditary spastic
      paraparesis.
AB  - BACKGROUND: Hereditary spastic paraparesis (HSP) is a group of rare genetic
      disorders affecting the central nervous system. Pure HSP is limited to lower limb
      spasticity and urinary voiding dysfunction. Complex HSP involves additional
      neurological features. Beyond the described core symptoms, knowledge about the
      burden of disease for adults with HSP is limited, particularly regarding
      gastrointestinal functions, fecal incontinence, and urinary symptoms. METHODS: We
      conducted a cross-sectional self-report survey with 108 adult HSP patients (Mage
      = 57.7 years, SD = 11.5, range 30 to 81; 54.2% females) recruited from a national
      HSP user group association and a national (non-clinical) advisory unit for rare
      disorders. HSP data was compared to data from a Norwegian population study, HUNT
      3 (N = 46,293). RESULTS: The HSP group reported more gastrointestinal and urinary
      complaints compared to controls. Gastrointestinal complaints included at least
      "much" complaints with constipation (14.6%) and alternating constipation/diarrhea
      (8.0%), and at least daily uncontrollable flatulence (47.6%), fecal incontinence
      (11.6%), and inability to hold back stools (38.5%). Urinary complaints included
      frequent urination (27.4% > 8 times daily), sudden urge (51.9%) and urinary
      incontinence (30.5% at least daily/nightly). CONCLUSION: This survey of adults
      with HSP recruited from non-clinical settings showed constipation, alternate
      constipation and diarrhea, fecal incontinence, and voiding dysfunction represent
      considerable problems for many persons with HSP. Health care providers should
      screen and manage often unrecognized gastrointestinal and fecal incontinence
      complaints among HSP patients.

PMID- 29661210
TI  - Use of a life-size three-dimensional-printed spine model for pedicle screw
      instrumentation training.
AB  - BACKGROUND: Training beginners of the pedicle screw instrumentation technique in
      the operating room is limited because of issues related to patient safety and
      surgical efficiency. Three-dimensional (3D) printing enables training or
      simulation surgery on a real-size replica of deformed spine, which is difficult
      to perform in the usual cadaver or surrogate plastic models. The purpose of this
      study was to evaluate the educational effect of using a real-size 3D-printed
      spine model for training beginners of the free-hand pedicle screw instrumentation
      technique. We asked whether the use of a 3D spine model can improve (1) screw
      instrumentation accuracy and (2) length of procedure. METHODS: Twenty life-size
      3D-printed lumbar spine models were made from 10 volunteers (two models for each
      volunteer). Two novice surgeons who had no experience of free-hand pedicle screw
      instrumentation technique were instructed by an experienced surgeon, and each
      surgeon inserted 10 pedicle screws for each lumbar spine model. Computed
      tomography scans of the spine models were obtained to evaluate screw
      instrumentation accuracy. The length of time in completing the procedure was
      recorded. The results of the latter 10 spine models were compared with those of
      the former 10 models to evaluate learning effect. RESULTS: A total of 37/200
      screws (18.5%) perforated the pedicle cortex with a mean of 1.7 mm (range, 1.2
      3.3 mm). However, the latter half of the models had significantly less violation
      than the former half (10/100 vs. 27/100, p < 0.001). The mean length of time to
      complete 10 pedicle screw instrumentations in a spine model was 42.8 +/- 5.3 min
      for the former 10 spine models and 35.6 +/- 2.9 min for the latter 10 spine
      models. The latter 10 spine models had significantly less time than the former 10
      models (p < 0.001). CONCLUSION: A life-size 3D-printed spine model can be an
      excellent tool for training beginners of the free-hand pedicle screw
      instrumentation.

PMID- 29661212
TI  - Numerical modeling of mosquito population dynamics of Aedes aegypti.
AB  - BACKGROUND: The global incidences of dengue virus have increased the interest in
      studying and understanding the mosquito population dynamics. It is predominantly
      spread by Aedes aegypti in the tropical and sub-tropical countries in the world.
      Understanding these dynamics is important for public health in countries where
      climatic and environmental conditions are favorable for the propagation of these
      diseases. For this reason, a new model has been proposed to investigate the
      population dynamics of mosquitoes in a city. METHODS: The present paper discusses
      the numerical modeling of population dynamics of Ae. aegypti mosquitoes in an
      urban neighborhood of a city using the finite volume method. The model describes
      how populations spread through the city assisted by the wind. This model allows
      incorporating external factors (wind and chemical insecticides) and topography
      data (streets, building blocks, parks, forests and beach). The proposed model has
      been successfully tested in examples involving two Brazilian cities (City center,
      Juiz de Fora and Copacabana Beach, Rio de Janeiro). RESULTS: Invasion phenomena
      of Ae. aegypti mosquitoes have been observed in each of the simulations. It was
      observed that, inside the blocks, the growth of the population for both winged
      and aquatic phase causes an infestation of Ae. aegypti in a short time. Within
      the blocks the mosquito population was concentrated and diffused slowly. In the
      streets, there was a long-distance spread, which was influenced by wind and
      diffusion with a low concentration of mosquito population. The model was also
      tested taking into account chemical insecticides spread in two different
      configurations. It has been observed that the insecticides have a significant
      effect on the mosquito population for both winged and aquatic phases when the
      chemical insecticides spread more uniformly along all the streets in a
      neighborhood of a city. CONCLUSIONS: The presented methodology can be employed to
      evaluate and to understand the epidemic risks in a specific region of the city.
      Moreover the model allows an increase in efficiency of the existing mosquito
      population control techniques and to theoretically test new methods before
      involving the human population.

PMID- 29661211
TI  - Predictive value of dynamic change of haemoglobin levels during therapy on
      treatment outcomes in patients with Enneking stage IIB extremity osteosarcoma.
AB  - BACKGROUND: We aimed to investigate the roles of hemoglobin (Hb) concentrations
      and dynamic change during treatment on outcomes of patients with extremity
      osteosarcoma. METHODS: We retrospectively analysed 133 patients with Enneking
      stage IIB extremity osteosarcoma who underwent standard treatments, including
      univariate and multivariate analyses of patient charateritics, Hb concentrations
      and changes during pretreatment, neoadjuvant, adjuvant chemotherapy, and
      decreased Hb levels (DeltaHb) to assess their prognostic value in 5-year overall
      survival (OS) and lung metastasis-free survival (LMFS). RESULTS: Five-year OS or
      LMFS were similar between patients who were anaemic and non-anaemic during
      pretreatment, neoadjuvant or adjuvant chemotherapy. Patients with continuously
      decreasing Hb had lower 5-year OS (52.3%) than those without continuous Hb
      decrease (68.5%, P = 0.04). Patients with DeltaHb > 7.6 g/L had lower 5-year OS
      (57.5%) than those with DeltaHb <=7.6 g/L (75.8%, P = 0.04). However, continuous
      Hb decrease had no prognostic effect on 5-year LMFS. Subgroup analyses showed
      that patients who were anaemic during pretreatment, neoadjuvant, or adjuvant
      chemotherapy with DeltaHb <=7.6 g/L had better outcomes than those with DeltaHb >
      7.6 g/L (P < 0.05, for both). CONCLUSION: Dynamic Hb decrease and DeltaHb > 7.6
      predicted poor5-year OS in patients with Enneking stage IIB extremity
      osteosarcoma. Attempts to correct anaemia and their effects on outcomes for
      osteosarcoma patients should be investigated in future trials.

PMID- 29661213
TI  - Sensitivity to sequencing depth in single-cell cancer genomics.
AB  - BACKGROUND: Querying cancer genomes at single-cell resolution is expected to
      provide a powerful framework to understand in detail the dynamics of cancer
      evolution. However, given the high costs currently associated with single-cell
      sequencing, together with the inevitable technical noise arising from single-cell
      genome amplification, cost-effective strategies that maximize the quality of
      single-cell data are critically needed. Taking advantage of previously published
      single-cell whole-genome and whole-exome cancer datasets, we studied the impact
      of sequencing depth and sampling effort towards single-cell variant detection.
      METHODS: Five single-cell whole-genome and whole-exome cancer datasets were
      independently downscaled to 25, 10, 5, and 1* sequencing depth. For each depth
      level, ten technical replicates were generated, resulting in a total of 6280
      single-cell BAM files. The sensitivity of variant detection, including structural
      and driver mutations, genotyping, clonal inference, and phylogenetic
      reconstruction to sequencing depth was evaluated using recent tools specifically
      designed for single-cell data. RESULTS: Altogether, our results suggest that for
      relatively large sample sizes (25 or more cells) sequencing single tumor cells at
      depths > 5* does not drastically improve somatic variant discovery,
      characterization of clonal genotypes, or estimation of single-cell phylogenies.
      CONCLUSIONS: We suggest that sequencing multiple individual tumor cells at a
      modest depth represents an effective alternative to explore the mutational
      landscape and clonal evolutionary patterns of cancer genomes.

PMID- 29661214
TI  - Does information from ClinicalTrials.gov increase transparency and reduce bias?
      Results from a five-report case series.
AB  - BACKGROUND: We investigated whether information in ClinicalTrials.gov would
      impact the conclusions of five ongoing systematic reviews. METHOD: We considered
      five reviews that included 495 studies total. Each review team conducted a search
      of ClinicalTrials.gov up to the date of the review's last literature search,
      screened the records using the review's eligibility criteria, extracted
      information, and assessed risk of bias and applicability. Each team then
      evaluated the impact of the evidence found in ClinicalTrials.gov on the
      conclusions in the review. RESULTS: Across the five reviews, the number of
      studies that had both a registry record and a publication varied widely, from
      none in one review to 43% of all studies identified in another. Among the studies
      with both a record and publication, there was also wide variability in the match
      between published outcomes and those listed in ClinicalTrials.gov. Of the 173
      total ClinicalTrials.gov records identified across the five projects, between 11
      and 43% did not have an associated publication. In the 14% of records that
      contained results, the new data provided in the ClinicalTrials.gov records did
      not change the results or conclusions of the reviews. Finally, a large number of
      published studies were not registered in ClinicalTrials.gov, but many of these
      were published before ClinicalTrials.gov's inception date of 2000. CONCLUSION:
      Improved prospective registration of trials and consistent reporting of results
      in ClinicalTrials.gov would help make ClinicalTrials.gov records more useful in
      finding unpublished information and identifying potential biases. In addition,
      consistent indexing in databases, such as MEDLINE, would allow for better
      matching of records and publications, leading to increased utility of these
      searches for systematic review projects.

PMID- 29661215
TI  - Recovering parasites from mummies and coprolites: an epidemiological approach.
AB  - In the field of archaeological parasitology, researchers have long documented the
      distribution of parasites in archaeological time and space through the analysis
      of coprolites and human remains. This area of research defined the origin and
      migration of parasites through presence/absence studies. By the end of the 20th
      century, the field of pathoecology had emerged as researchers developed an
      interest in the ancient ecology of parasite transmission. Supporting studies were
      conducted to establish the relationships between parasites and humans, including
      cultural, subsistence, and ecological reconstructions. Parasite prevalence data
      were collected to infer the impact of parasitism on human health. In the last few
      decades, a paleoepidemiological approach has emerged with a focus on applying
      statistical techniques for quantification. The application of egg per gram (EPG)
      quantification methods provide data about parasites' prevalence in ancient
      populations and also identify the pathological potential that parasitism
      presented in different time periods and geographic places. Herein, we compare the
      methods used in several laboratories for reporting parasite prevalence and EPG
      quantification. We present newer quantification methods to explore patterns of
      parasite overdispersion among ancient people. These new methods will be able to
      produce more realistic measures of parasite infections among people of the past.
      These measures allow researchers to compare epidemiological patterns in both
      ancient and modern populations.

PMID- 29661216
TI  - Angiotensin II for the treatment of vasodilatory shock: enough data to consider
      angiotensin II safe?

PMID- 29661217
TI  - Barriers to access and utilization of emergency obstetric care at health
      facilities in sub-Saharan Africa-a systematic review protocol.
AB  - BACKGROUND: Nearly 15% of all pregnancies end in fatal perinatal obstetric
      complications including bleeding, infections, hypertension, obstructed labor, and
      complications of abortion. Between 1990 and 2015, an estimated 10.7 million women
      died due to obstetric complications. Almost all of these deaths (99%) happened in
      developing countries, and 66% of maternal deaths were attributed to sub-Saharan
      Africa. The majority of cases of maternal mortalities can be prevented through
      provision of evidence-based potentially life-saving signal functions of emergency
      obstetric care. However, different factors can hinder women's ability to access
      and use emergency obstetric services in sub-Saharan Africa. Therefore, the aim of
      this review is to synthesize current evidence on barriers to accessing and
      utilizing emergency obstetric care in sub-Saharan African. Decision-makers and
      policy formulators will use evidence generated from this review in improving
      maternal healthcare particularly the emergency obstetric care. METHODS:
      Electronic databases including MEDLINE, CINAHL, Embase, and Maternity and Infant
      Care will be searched for studies using predefined search terms. Articles
      published in English language between 2010 and 2017 with quantitative and
      qualitative design will be included. The identified papers will be assessed for
      meeting eligibility criteria. First, the articles will be screened by examining
      their titles and abstracts. Then, two reviewers will review the full text of the
      selected articles independently. Two reviewers using a standard data extraction
      format will undertake data extraction from the retained studies. The quality of
      the included papers will be assessed using the mixed methods appraisal tool.
      Results from the eligible studies will be qualitatively synthesized using the
      narrative synthesis approach and reported using the three delays model. The
      Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist will
      be employed to present the findings. DISCUSSION: This systematic review will
      present a detailed synthesis of the evidence for barriers to access and
      utilization of emergency obstetric care in sub-Saharan Africa over the last 7
      years. This systematic review is expected to provide clear information that can
      help in designing maternal health policy and interventions particularly in
      emergency obstetric care in sub-Saharan Africa where maternal mortality remains
      high. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017074102 .

PMID- 29661218
TI  - ENdometrial cancer SURvivors' follow-up carE (ENSURE): Less is more? Evaluating
      patient satisfaction and cost-effectiveness of a reduced follow-up schedule:
      study protocol of a randomized controlled trial.
AB  - BACKGROUND: It has often been hypothesized that the frequency of follow-up visits
      for patients with early-stage endometrial cancer could be decreased. However,
      studies evaluating effects of a reduced follow-up schedule among this patient
      group are lacking. The aim of this study is to assess patient satisfaction and
      cost-effectiveness of a less frequent follow-up schedule compared to the schedule
      according to the Dutch guideline. METHODS: In this multicenter randomized
      controlled trial, patients diagnosed in the Netherlands with stage 1A and 1B low
      risk endometrial cancer, for whom adjuvant radiotherapy is not indicated (n =
      282), are randomized. Patients allocated to the intervention group receive four
      follow-up visits during three years. Patients allocated to the control group
      receive 10-13 follow-up visits during five years, according to the Dutch
      guideline. Patients are asked to fill out a questionnaire at baseline and after
      6, 12, 36, and 60 months. Primary outcomes include patient satisfaction with
      follow-up care and cost-effectiveness. Secondary outcomes include healthcare use,
      adherence to schedule, health-related quality of life, fear of recurrence,
      anxiety and depression, information provision, recurrence, and survival. Linear
      regression analyses will be used to assess differences in patient satisfaction
      with follow-up care between intervention and control group. DISCUSSION: We
      anticipate that patients in the intervention arm have a similar satisfaction with
      follow-up care and overall outcomes, but lower healthcare use and costs than
      patients in the control arm. No differences are expected in quality-adjusted life
      years and satisfaction, but the reduced schedule is expected to be cost-saving
      when implemented in the Netherlands. TRIAL REGISTRATION: ClinicalTrials.gov,
      NCT02413606 . Registered on 10 April 2015.

PMID- 29661219
TI  - Modulation of GSK-3 provides cellular and functional neuroprotection in the rd10
      mouse model of retinitis pigmentosa.
AB  - BACKGROUND: Retinitis pigmentosa (RP) is a group of hereditary retinal
      neurodegenerative conditions characterized by primary dysfunction and death of
      photoreceptor cells, resulting in visual loss and, eventually, blindness. To
      date, no effective therapies have been transferred to clinic. Given the diverse
      genetic etiology of RP, targeting common cellular and molecular retinal
      alterations has emerged as a potential therapeutic strategy. METHODS: Using the
      Pde6b rd10/rd10 mouse model of RP, we investigated the effects of daily
      intraperitoneal administration of VP3.15, a small-molecule heterocyclic GSK-3
      inhibitor. Gene expression was analyzed by quantitative PCR and protein
      expression and phosphorylation by Western blot. Photoreceptor preservation was
      evaluated by histological analysis and visual function was assessed by
      electroretinography. RESULTS: In rd10 retinas, increased expression of pro
      inflammatory markers and reactive gliosis coincided with the early stages of
      retinal degeneration. Compared with wild-type controls, GSK-3beta expression
      (mRNA and protein) remained unchanged during the retinal degeneration period.
      However, levels of GSK-3betaSer9 and its regulator AktSer473 were increased in
      rd10 versus wild-type retinas. In vivo administration of VP3.15 reduced
      photoreceptor cell loss and preserved visual function. This neuroprotective
      effect was accompanied by a decrease in the expression of neuroinflammatory
      markers. CONCLUSIONS: These results provide proof of concept of the therapeutic
      potential of VP3.15 for the treatment of retinal neurodegenerative conditions in
      general, and RP in particular.

PMID- 29661220
TI  - Asymmetrical degenerative marrow (Modic) changes in cervical spine: prevalence,
      correlative factors, and surgical outcomes.
AB  - BACKGROUND: The current study aimed to discuss the prevalence and surgical
      outcomes of the asymmetrical Modic changes and identify its correlative factors
      by multivariate logistic regression analysis. METHODS: Two hundred seventy-eight
      patients with single-level Modic changes and nerve compression symptoms were
      reviewed retrospectively from January 2008 to January 2015. 1.5-T MRI was
      performed to determine the Modic changes. Multivariate logistic regression
      analysis was used to identify the correlative factors of asymmetrical Modic
      changes. Surgeries were performed according to the surgical indications. The
      outcomes were recorded by Japanese Orthopaedic Association (JOA) score, Neck
      Disability Index (NDI) score, and recovery rate. RESULTS: Asymmetrical Modic
      changes were observed in 76 patients (27.34%) with 4 type 1, 69 type 2, and 3
      type 3. C5/6 was the most frequently affected segment with 39 patients showing
      signal changes on MRI. Statistically significant difference was showed in
      conservative rehabilitation rate between two groups (p = 0.043). Multiple
      logistic regression analysis identified disc herniation and neurological symptoms
      as correlative factors of asymmetrical Modic changes, and the adjusted odds
      ratios (95% CI) were 2.079 (1.348-3.208) and 0.231 (0.143-0.373) respectively. No
      statistically significant difference was found in JOA scores and NDI scores
      between the two kinds of Modic changes. CONCLUSIONS: C5/6 was the most commonly
      affected level by Modic changes. Disc herniation and nerve root compression
      symptom were more closely correlated with asymmetrical Modic changes than
      conventional Modic changes. Asymmetrical Modic changes indicated poor result in
      conservative treatment; however, the final operation rate was similar between the
      two kinds of Modic changes. The outcomes of surgical treatment were satisfactory
      both in patients with asymmetrical Modic changes and conventional Modic changes.

PMID- 29661221
TI  - Practice patterns and outcomes for patients with node-negative hormone receptor
      positive breast cancer and intermediate 21-gene Recurrence Scores.
AB  - BACKGROUND: The recommendation for chemotherapy in early-stage breast cancer
      patients has been refined by the 21-gene Recurrence Score. However, uncertainty
      remains whether patients in the Intermediate Risk category benefit from
      chemotherapy. METHODS: We analyzed female patients from the National Cancer
      Database from 2006 to 2012 who had pT1c-T2N0M0 breast cancer, were ER/PR-positive
      and HER2-negative, received endocrine therapy, and had a 21-gene Recurrence Score
      from 11 to 25. We performed univariate and multivariate logistic regression
      analyses to see what impacted chemotherapy receipt. We compared overall survival
      using Kaplan-Meier curves and the log-rank test. A multivariable Cox proportional
      hazards regression model was used to assess what variables impacted overall
      survival. RESULTS: Of 21,991 patients who met all inclusion and exclusion
      criteria, 4646 (21.1%) received chemotherapy and 17,345 (78.9%) did not.
      Chemotherapy was more often received by patients who were younger (adjusted odds
      ratios (aORs) compared to age < 40 years, 0.48 for 40s, 0.34 for 50s, 0.20 for
      60s, 0.10 for 70s, and 0.07 for 80+), had private insurance vs Medicare (aOR =
      1.37), were from metro vs urban counties (aOR = 1.15), and were treated in
      community cancer centers vs academic programs (aOR = 1.26), and those with tumors
      of higher grade (grade 2 vs 1, aOR = 1.72; grade 3 vs 1, aOR = 3.76), higher
      tumor stage (pT2 vs pT1c, aOR = 1.62), or presence of lymphovascular invasion
      (LVI) (aOR = 1.41). At a median follow-up of 46.4 months, there was no
      significant difference in overall survival between patients who received
      chemotherapy vs those who did not (5-year estimated overall survival, 97.4% vs
      97.8%, p = 0.89). On multivariable analysis, worse overall survival was
      associated with Black race, treatment at a community program, Medicaid, high
      grade tumors, pT2 vs pT1c, higher Charlson-Deyo score, and no radiotherapy.
      Utilization trends showed that chemotherapy receipt in these patients has been
      decreasing from 25.8% in 2010 to 18.4% in 2013 (p < 0.001). CONCLUSIONS: In these
      patients where the benefit of chemotherapy remains uncertain, current practices
      see chemotherapy more likely to be used in patients with younger age, higher
      pathologic T stage, higher grade tumors, and LVI. No apparent difference was seen
      in overall survival between those who received chemotherapy and those who did
      not.

PMID- 29661222
TI  - Platelet-rich plasma enhances the proliferation of human adipose stem cells
      through multiple signaling pathways.
AB  - BACKGROUND: Platelet-rich plasma (PRP) is an autologous blood product that
      contains a high concentration of several growth factors. Platelet-derived growth
      factor (PDGF)-BB is a potential mitogen for human adipose-derived stem cells
      (hASCs). PRP stimulates proliferation of hASCs; however, the signaling pathways
      activated by PRP remain unclear. METHODS: hASCs were cultured with or without PRP
      or PDGF-BB, and proliferation was assessed. hASCs were also treated with PRP or
      PDGF-BB with or without imatinib, which is a PDGF receptor tyrosine kinase
      inhibitor, or sorafenib, which is a multikinase inhibitor. Inhibition of cell
      proliferation was examined using anti-PDGF antibody (Abcam, Cambridge, UK), by
      cell counting. We assessed the effects of inhibitors of various protein kinases
      such as ERK1/2, JNK, p38, and Akt on the proliferation of hASCs. RESULTS: The
      proliferation was remarkably promoted in cells treated with either 1% PRP or 10
      ng/ml PDGF-BB, and both imatinib and sorafenib inhibited this proliferation. Anti
      PDGF antibody (0.5 and 2 MUg/ml) significantly decreased the proliferation of
      hASCs compared with control. PRP-mediated hASC proliferation was blocked by
      inhibitors of ERK1/2, Akt, and JNK, but not by an inhibitor of p38. CONCLUSIONS:
      PRP promotes hASC proliferation, and PDGF-BB in PRP plays a major role in
      inducing the proliferation of hASCs. PRP promotes hASC proliferation via ERK1/2,
      PI3K/Akt, and JNK signaling pathways.

PMID- 29661223
TI  - Youth's social network structures and peer influences: study protocol MyMovez
      project - Phase I.
AB  - BACKGROUND: Youth are an important target group for social network interventions,
      because they are particularly susceptible to the adaptation of healthy and
      unhealthy habits and behaviors of others. They are surrounded by 'social
      influence agents' (i.e., role models such as family, friends and peers) that co
      determine their dietary intake and physical activity. However, there is a lack of
      systematic and comprehensive research on the implementation of a social network
      approach in health campaigns. The MyMovez research project aims to fill this gap
      by developing a method for effective social network campaign implementation. This
      protocol paper describes the design and methods of Phase I of the MyMovez
      project, aiming to unravel youth's social network structures in combination with
      individual, psychosocial, and environmental factors related to energy intake and
      expenditure. In addition, the Wearable Lab is developed to enable an attractive
      and state-of-the-art way of collecting data and online campaign implementation
      via social networks. METHODS: Phase I of the MyMovez project consists of a large
      scale cross-sequential cohort study (N = 953; 8-12 and 12-15 y/o). In five waves
      during a 3-year period (2016-2018), data are collected about youth's social
      network exposure, media consumption, socialization experiences, psychological
      determinants of behavior, physical environment, dietary intake (snacking and
      drinking behavior) and physical activity using the Wearable Lab. The Wearable Lab
      exists of a smartphone-based research application (app) connected to an activity
      tracking bracelet, that is developed throughout the duration of the project. It
      generates peer- and self-reported (e.g., sociometric data and surveys) and
      experience sampling data, social network beacon data, real-time physical activity
      data (i.e., steps and cycling), location information, photos and chat
      conversation data from the app's social media platform Social Buzz. DISCUSSION:
      The MyMovez project - Phase I is an innovative cross-sequential research project
      that investigates how social influences co-determine youth's energy intake and
      expenditure. This project utilizes advanced research technologies (Wearable Lab)
      that provide unique opportunities to better understand the underlying processes
      that impact youths' health-related behaviors. The project is theoretically and
      methodologically pioneering and produces a unique and useful method for
      successfully implementing and improving health campaigns.

PMID- 29661224
TI  - Notch signals modulate lgl mediated tumorigenesis by the activation of JNK
      signaling.
AB  - OBJECTIVES: Oncogenic potential of Notch signaling and its cooperation with other
      factors to affect proliferation are widely established. Notch exhibits a
      cooperative effect with loss of a cell polarity gene, scribble to induce
      neoplastic overgrowth. Oncogenic Ras also show cooperative effect with loss of
      cell polarity genes such as scribble (scrib), lethal giant larvae (lgl) and discs
      large to induce neoplastic overgrowth and invasion. Our study aims at assessing
      the cooperation of activated Notch with loss of function of lgl in tumor
      overgrowth, and the mode of JNK signaling activation in this context. RESULTS: In
      the present study, we use Drosophila as an in vivo model to show the synergy
      between activated Notch (N act ) and loss of function of lgl (lgl-IR) in tumor
      progression. Coexpression of N act and lgl-IR results in massive tumor overgrowth
      and displays hallmarks of cancer, such as MMP1 upregulation and loss of
      epithelial integrity. We further show activation of JNK signaling and
      upregulation of its receptor, Grindelwald in N act /lgl-IR tumor. In contrast to
      previously described Notch act /scrib-/- tumor, our experiments in N act /lgl-IR
      tumor showed the presence of dying cells along with tumorous overgrowth.

PMID- 29661225
TI  - Lymphocyte subset expression and serum concentrations of PD-1/PD-L1 in sepsis -
      pilot study.
AB  - BACKGROUND: Sepsis remains a major cause of mortality in critical care, for which
      specific treatments are lacking. The dysregulated response to infection seen in
      sepsis includes features of lymphocyte dysfunction and exhaustion, suggesting
      that immune-stimulatory therapy may improve outcomes in certain patient groups.
      Monoclonal antibodies targeting checkpoint molecules, such as programmed-death 1
      protein (PD-1) and its ligand PD-L1, have shown success in stimulating the immune
      response in patients with cancer, and are being considered for future sepsis
      trials. The aims of this pilot study were to compare lymphocyte subset expression
      of PD-1 and its ligands between patients with sepsis and controls; to
      characterize serum levels of PD-1 and PD-L1 in patients with sepsis and controls,
      and determine if serum concentrations correlated with cell surface expression.
      METHODS: Expression levels of PD-1, PD-L1 and PD-L2 on four lymphocyte subsets
      (CD27 + CD19+ B cells, CD27-CD19+ B cells, CD27 + CD4+ T cells and CD27-CD4+ T
      cells) were compared between 22 patients with sepsis (including 11 survivors and
      11 non-survivors) and 11 healthy controls using flow cytometry. Levels of soluble
      PD-1 and PD-L1 were also compared using commercially available ELISA kits.
      RESULTS: Expression of PD-1 and PD-L1 was higher on all lymphocyte subsets in
      patients with sepsis compared to controls (p < 0.05). PD-L2 expression on CD27+ B
      cells was also higher in patients with sepsis (p = 0.0317). There was
      differential expression of PD-1 by CD27 status, with expression being higher in
      the B and T cell subsets associated with memory status (CD27+ and CD27-,
      respectively; p < 0.001). Higher PD-1 and PD-L1 expression was not associated
      with mortality or with a higher risk of nosocomial infection. There were no
      differences in levels of soluble PD-1 or PD-L1 between patients with sepsis and
      controls. CONCLUSIONS: Higher expression of PD-1 by memory subpopulations of B
      cells and CD4+ T cells, with normal soluble PD-1 and PD-L1 in patients with
      sepsis, are novel findings. This information may be useful to enrich sepsis
      populations for trials of PD-1/PD-L1 blockade.

PMID- 29661226
TI  - Spatio-temporal genetic structure of Anopheles gambiae in the Northwestern Lake
      Victoria Basin, Uganda: implications for genetic control trials in malaria
      endemic regions.
AB  - BACKGROUND: Understanding population genetic structure in the malaria vector
      Anopheles gambiae (s.s.) is crucial to inform genetic control and manage
      insecticide resistance. Unfortunately, species characteristics such as high
      nucleotide diversity, large effective population size, recent range expansion,
      and high dispersal ability complicate the inference of genetic structure across
      its range in sub-Saharan Africa. The ocean, along with the Great Rift Valley, is
      one of the few recognized barriers to gene flow in this species, but the effect
      of inland lakes, which could be useful sites for initial testing of genetic
      control strategies, is relatively understudied. Here we examine Lake Victoria as
      a barrier between the Ugandan mainland and the Ssese Islands, which lie up to 60
      km offshore. We use mitochondrial DNA (mtDNA) from populations sampled in 2002,
      2012 and 2015, and perform Bayesian cluster analysis on mtDNA combined with
      microsatellite data previously generated from the same 2002 mosquito DNA samples.
      RESULTS: Hierarchical analysis of molecular variance and Bayesian clustering
      support significant differentiation between the mainland and lacustrine islands.
      In an mtDNA haplotype network constructed from this and previous data, haplotypes
      are shared even between localities separated by the Rift Valley, a result that
      more likely reflects retention of shared ancestral polymorphism than contemporary
      gene flow. CONCLUSIONS: The relative genetic isolation of An. gambiae on the
      Ssese Islands, their small size, level terrain and ease of access from the
      mainland, the relative simplicity of the vectorial system, and the prevalence of
      malaria, are all attributes that recommend these islands as possible sites for
      the testing of genetic control strategies.

PMID- 29661227
TI  - Correction to: Engaging policy-makers, health system managers, and policy
      analysts in the knowledge synthesis process: a scoping review.
AB  - Following the publication of the original article [1], it was brought to our
      attention that the letter 'l' was unfortunately omitted from the word 'health' in
      the article's title.

PMID- 29661228
TI  - MiR-760 suppresses human colorectal cancer growth by targeting BATF3/AP
      1/cyclinD1 signaling.
AB  - BACKGROUND: Recent studies have reported that microRNAs (miRNAs) often function
      as negative post-transcriptional regulators with altered expression levels found
      in colorectal cancer (CRC). There have been few studies on miRNAs that regulate
      the oncogenic alterations in CRC. Here, we aim to explore the anti-cancer miRNA
      and the potential mechanisms by which miRNAs modulate CRC progression. METHODS:
      We performed an integrated analysis of CRC miRNA expression datasets in The
      Cancer Genome Atlas (TCGA). The miRNA with the lowest expression, miR-760, was
      validated in an independent validation sample cohort of 76 CRC tissues.
      Functional assays, such as CCK-8 assay, colony formation assay, and CFSE
      staining, were used to determine the oncogenic role of miR-760 in human CRC
      progression. Furthermore, western blotting and dual-luciferase reporter assay
      were used to determine the mechanism by which miR-760 promotes proliferation of
      CRC cells. Xenograft nude mouse models were used to determine the role of miR-760
      in CRC tumorigenicity in vivo. Immunohistochemical assays were conducted to study
      the relationship between miR-760 expression and basic leucine zipper
      transcriptional factor ATF-like 3 (BATF3) expression in human CRC samples.
      RESULTS: miR-760 was markedly downregulated in CRC tissues, and low miR-760
      expression was associated with poor prognosis among CRC patients. Upregulation of
      miR-760 suppressed CRC cell proliferation, whereas downregulation of miR-760
      promoted CRC proliferation in vitro. Additionally, we identified BATF3 as a
      direct target of miR-760, and that the essential biological function of miR-760
      during CRC progression both in vitro and in vivo is to suppress the expression of
      BATF3 and downstream cyclinD1 via AP-1 transcription factor. Finally, we showed a
      significant correlation between miR-760 and BATF3 expression in CRC tissues.
      CONCLUSIONS: miR-760 inhibited CRC growth by downregulating BATF3/AP-1/ cyclinD1
      signaling.

PMID- 29661229
TI  - Can Arthroplasty Stem INfluence Outcome? (CASINO): a randomized controlled
      equivalence trial of 125 mm versus 150 mm Exeter V40 stems in total hip
      arthroplasty.
AB  - BACKGROUND: The use of shorter length femoral stems during total hip arthroplasty
      has been suggested to accommodate wider patient femoral geometry and offer
      maximal bone preservation. However, cemented short-stem designs may increase the
      risk of varus stem malalignment and influence patient outcomes. METHODS/DESIGN:
      CASINO is a multi-centre randomised equivalence trial that will recruit 220
      patients undergoing total hip arthroplasty for osteoarthritis at two NHS
      hospitals in Scotland. Patients will be aged 45-80, undergoing unilateral primary
      hip arthroplasty, with no plan for contralateral procedure within the study
      timeframe, and able to comply with the protocol. Participants will be randomised
      to receive either a short (125 mm) or a standard (150 mm) Exeter V40 stem. The
      Contemporary acetabular component will be used in all cases. All implants will be
      cemented. Patient pain, function and satisfaction will be assessed using change
      from baseline measurement in Oxford Hip Score, Forgotten Joint Score, EQ-5D, pain
      numerical rating scores, and patient satisfaction questionnaire at baseline and
      at 1 and 2 years following surgery. Radiographic assessment will evaluate stem
      position and will be appraised by independent reviewers. Patients will be blind
      to implant allocation. DISCUSSION: Stem length may be associated with outcome;
      however, we can find no randomised trial in which researchers investigated the
      effect of stem length on patient outcome following cemented total hip
      arthroplasty. The aim of this trial is to determine if the use of short cemented
      stems offers equivalent patient outcomes to those achieved following surgery with
      standard length stems. TRIAL REGISTRATION: International Standard Randomised
      Controlled Trial Number, ISRCTN13154542 , Registered on 30 June 2017.

PMID- 29661230
TI  - A comparison of methods used to unveil the genetic and metabolic pool in the
      built environment.
AB  - BACKGROUND: A majority of indoor residential microbes originate from humans,
      pets, and outdoor air and are not adapted to the built environment (BE).
      Consequently, a large portion of the microbes identified by DNA-based methods are
      either dead or metabolically inactive. Although many exceptions have been noted,
      the ribosomal RNA fraction of the sample is more likely to represent either
      viable or metabolically active cells. We examined methodological variations in
      sample processing using a defined, mock BE microbial community to better
      understand the scope of technique-based vs. biological-based differences in both
      ribosomal transcript (rRNA) and gene (DNA) sequence community analysis. Based on
      in vitro tests, a protocol was adopted for the analysis of the genetic and
      metabolic pool (DNA vs. rRNA) of air and surface microbiomes within a residential
      setting. RESULTS: We observed differences in DNA/RNA co-extraction efficiency for
      individual microbes, but overall, a greater recovery of rRNA using FastPrep (>
      50%). Samples stored with various preservation methods at - 80 degrees C
      experienced a rapid decline in nucleic acid recovery starting within the first
      week, although post-extraction rRNA had no significant degradation when treated
      with RNAStable. We recommend that co-extraction samples be processed as quickly
      as possible after collection. The in vivo analysis revealed significant
      differences in the two components (genetic and metabolic pool) in terms of
      taxonomy, community structure, and microbial association networks. Rare taxa
      present in the genetic pool showed higher metabolic potential (RNA:DNA ratio),
      whereas commonly detected taxa of outdoor origins based on DNA sequencing,
      especially taxa of the Sphingomonadales order, were present in lower relative
      abundances in the viable community. CONCLUSIONS: Although methodological
      variations in sample preparations are high, large differences between the DNA and
      RNA fractions of the total microbial community demonstrate that direct
      examination of rRNA isolated from a residential BE microbiome has the potential
      to identify the more likely viable or active portion of the microbial community.
      In an environment that has primarily dead and metabolically inactive cells, we
      suggest that the rRNA fraction of BE samples is capable of providing a more
      ecologically relevant insight into the factors that drive indoor microbial
      community dynamics.

PMID- 29661231
TI  - Surveillance for lymphatic filariasis after stopping mass drug administration in
      endemic districts of Togo, 2010-2015.
AB  - BACKGROUND: Togo is a country previously endemic for lymphatic filariasis (LF).
      In 2010, following nine years of mass drug administration (MDA) for LF, the
      country established a post-treatment surveillance (PTS) system. We present here
      the results of these PTS activities, carried out from 2010 to 2015, as well as
      the findings of follow-up investigations in 2016 to confirm the absence of
      infection in previously infected individuals. METHODS: The routine surveillance
      established in 2010 consisted of a network of 47 laboratories, which searched for
      Wuchereria bancrofti microfilaria on nocturnal blood smears collected for malaria
      diagnosis and an additional network of 20 peripheral health facilities, which
      collected dried blood spots and tested them for Og4C3 antigen. Two transmission
      assessment surveys (TAS) were also undertaken, as recommended by WHO, in 2012 and
      2015. Any positive case identified through any surveillance activity was
      immediately retested by nocturnal smear and confirmed cases were immediately
      investigated by screening family members and neighboring household members. In
      2016, 32 of the 40 positive cases detected during TAS or laboratory and health
      facility network activities were traced and whether confirmed positive by
      nocturnal smear or not were tested again simultaneously by filariasis test strip
      (FTS), Og4C3 and a nocturnal blood smear to rule out any active infection.
      RESULTS: From 2010 to 2015, the laboratory network identified one microfilaria
      positive individual (0.0% of 26,584 persons tested) and the peripheral health
      facility network detected 19 Og4C3-positive individuals (0.28% of 6788 persons
      tested). All 19 Og4C3 cases were negative for microfilaremia by nocturnal blood
      smear. In the 2012 and 2015 TAS, thirteen and six ICT/FTS positive cases,
      respectively, were identified, which were significantly below the critical cut
      off (18-20 cases) across all evaluation units. Three of the six ICT/FTS-positive
      cases from the 2015 TAS were positive by nocturnal smear; immediate investigation
      identified one additional microfilaria-positive individual. Epidemiological
      investigation revealed that four of the five cases of microfilaremia were
      imported from another country in the region. In 2016, 32 of the 40 positive cases
      detected by at least one test during all surveillance activities were traced:
      four (12.5%) individuals were still positive by FTS but all 32 individuals were
      negative for microfilaremia and Og4C3 antigen. CONCLUSION: The results of post
      treatment surveillance in Togo have demonstrated that W. bancrofti filariasis is
      no longer of public health concern in Togo, more than six years after stopping
      MDA. Every possible effort should be made to maintain surveillance in order to
      promptly detect any resurgence and preserve this achievement.

PMID- 29661233
TI  - Effectiveness of government strategies for financial protection against costs of
      hospitalization Care in India.
AB  - BACKGROUND: In the past decade, India has seen the introduction of many 'publicly
      funded health insurance' schemes (PFHIs) that claim to cover approximately 300
      million people and are essentially forms of purchasing care from both public and
      private providers to reduce out-of-pocket expenditure (OOPE) for hospitalization.
      METHODS: Data from a recent government-organized nationwide household survey, The
      National Sample Survey 71st Round, were used to analyse the effectiveness and
      equity of tax-funded public health services and PFHIs as distinct but overlapping
      approaches to financial protection for hospitalization across different socio
      economic categories. Cross-tabulation analysis, multivariate logistic regression
      and propensity score matching were the main analytical methods used. RESULTS:
      Government hospitals provide access to 45.6% of all hospitalization needs.
      Although poorer quintiles use public hospitals more often, even in the poorest
      quintile, as many as 37.2% are utilizing private hospitals. The average OOPE that
      a household experiences for hospitalization in public hospitals is approximately
      only one-fifth of the OOPE for hospitalization in the private sector. PFHI
      schemes cover 12.8% of the population, and coverage is higher in upper quintiles
      and in urban areas. Hospitalization rates increase with PFHI coverage, and this
      occurs with both public and private providers. Propensity score matching shows
      that PFHI contributes to a marginal reduction (1%) in 'catastrophic health
      expenditure incidence at the 25% threshold' (CHE-25) for the bottom three
      quintiles. The reported coverage of PFHIs was greater in the upper income
      quintiles. Utilization of public services was greater in the poorer income
      quintiles and more marginalized social groups. CONCLUSIONS: Periodic surveys are
      essential to guide policy choices regarding the appropriate mix of strategies for
      financial protection in pluralistic systems. There is a need for caution
      regarding any shift in the role of governments from providing services to
      purchasing care, given the contexts and limitations of currently available PFHIs.
      Even with tax-funded public services, although the average OOPE is lower than the
      care purchased through PFHIs, there is still a modest level of CHE and
      impoverishment due to health care costs that persist. Both strategies need to be
      synergized for more effective financial protection.

PMID- 29661232
TI  - CMPD1 inhibited human gastric cancer cell proliferation by inducing apoptosis and
      G2/M cell cycle arrest.
AB  - BACKGROUND: Gastric cancer occupies the fourth highest morbidity rate of cancers
      worldwide. Clinical therapies of gastric cancer remain limited because of
      uncertainty of mechanisms and shortness of effective medicine. Thus, new drug
      candidates for gastric cancer treatment is urgently needed. RESULTS: In this
      study, CMPD1 as a wildly used MK2 phosphorylation inhibitor was employed to find
      its impact on gastric cancer cell proliferation, apoptosis and cell cycle using
      colony formation assay and flow cytometry analysis. Along with its anti
      proliferation effect on gastric cancer cell line MKN-45 and SGC7901, CMPD1 also
      induced massive apoptosis and significant G2/M phase arrest in a time-dependent
      and dose-dependent manner in MKN-45 cells respectively. Furthermore, Western blot
      confirmed that the expression of anti-apoptotic proteins Bcl-2 was decreased
      while BAX, cytochrome c release and cleaved PARP were increased. In addition,
      oncogene c-Myc was downregulated in response to CMPD1 treatment. CONCLUSIONS: Our
      results demonstrated that CMPD1 has anti-tumor effect on human gastric cancer
      cell line MKN-45 possibly via downregulating oncogene c-Myc expression and CMPD1
      could be applied as a potential candidate for treating gastric malignancy. To the
      best of our knowledge, it is the first report of anti-tumor effect of CMPD-1 on
      human gastric cancer cells.

PMID- 29661234
TI  - Characterization of serious adverse drug reactions as cause of emergency
      department visit in children: a 5-years active pharmacovigilance study.
AB  - BACKGROUND: To describe frequency, preventability and seriousness of adverse drug
      reactions (ADRs) in children as cause of emergency department (ED) admission and
      to evaluate the association between specific factors and the reporting of ADRs.
      METHODS: A retrospective analysis based on reports of suspected ADRs collected
      between January 1st, 2012 and December 31st, 2016 in the ED of Meyer Children's
      Hospital (Italy). Demographics, clinical status, suspected drugs, ADR
      description, and its degree of seriousness were collected. Logistic regression
      was used to estimate the reporting odds ratios (RORs) with 95% confidence
      intervals (CIs) of potential predictors of ADR seriousness. RESULTS: Within 5
      years, we observed 834 ADRs (1100 drug-ADR pairs), of whom 239 were serious; of
      them, 224 led to hospitalization. Patients were mostly treated with one drug.
      Among patients treated with more than one drug, 78 ADRs presented a potential
      interaction. The most frequently reported ADRs involved gastrointestinal system.
      The most frequently reported medication class was antinfectives. Risk of serious
      ADR was significantly lower in children and infants compared to adolescents (ROR
      0.41 [95% CI: 0.27-0.61] and 0.47 [0.32-0.71], respectively), and it was
      significantly increased in subjects exposed to more than one drug (ROR 1.87 [1.33
      2.62] and 3.01 [2.07-4.37] for subjects exposed to 2 and 3 or more drugs,
      respectively). Gender, interactions and off-label drug use did not influence the
      risk of serious ADRs. CONCLUSION: Active surveillance in pharmacovigilance might
      represent the best strategy to estimate and characterize the clinical burden of
      ADRs in children.

PMID- 29661235
TI  - Presence of novel triple mutations in the pvdhfr from Plasmodium vivax in
      Mangaluru city area in the southwestern coastal region of India.
AB  - BACKGROUND: Genes encoding dihydrofolate reductase (dhfr) and dihydropteroate
      synthase (dhps) are the targets of sulfadoxine-pyrimethamine (SP) present in
      artemisinin based combination therapy (ACT; artesunate + sulfadoxine
      pyrimethamine) for Plasmodium falciparum. Although SP is generally not used to
      treat vivax infection, mutations in dhfr and dhps that confer antifolate
      resistance in Plasmodium vivax are common; which may be attributed to its
      sympatric existence with P. falciparum. Current study was aimed to determine the
      pattern of mutations in dhfr and dhps in P. vivax isolates from Mangaluru region.
      METHODS: A total of 140 blood samples were collected from P. vivax-infected
      people attending Wenlock Hospital Mangaluru during July 2014 to January 2016. Out
      of 140 isolates, 25 (18%) and 50 (36%) isolates were selected randomly for
      sequence analysis of pvdhfr and pvdhps genes respectively. Fragment of pvdhps and
      full length pvdhfr were amplified, sequenced and analysed for single nucleotide
      polymorphisms. dhps was analysed by PCR-RFLP also, to detect the two specific
      mutations (A383G and A553G). RESULTS: Analysis of pvdhps sequences from 50
      isolates revealed single and double mutants at 38 and 46% respectively. Three non
      synonymous mutations (K55R, S58R and S117N) were identified for pvdhfr. Among
      these, K55R was detected for the first time. CONCLUSIONS: The current study
      indicates that P. vivax dhps and dhfr mutant alleles are prevalent in this area,
      suggesting significant SP pressure.

PMID- 29661236
TI  - Clinical analysis of 50 patients with heterotopic pregnancy after ovulation
      induction or embryo transfer.
AB  - OBJECTIVES: The purpose of this study was to evaluate the clinical
      characteristics, prenatal diagnosis, and management of patients with heterotopic
      pregnancy after ovulation induction or embryo transfer. METHODS: This was a
      retrospective study of fifty cases with heterotopic pregnancy, in which the
      fertilization way, type and number of embryo transferred, gestational age,
      clinical presentation and outcome of intrauterine, ultrasound presentation and
      site of ectopic pregnancy, bilateral fallopian tube and treatment were evaluated.
      RESULTS: Six patients had spontaneous pregnancy and two had artificial
      insemination after ovulation induction. Sixteen had fresh and nineteen had frozen
      embryo transfer with seven patients unrecorded its embryo type and number. The
      average days from transplantation (or intercourse/insemination) to diagnosing
      heterotopic pregnancy was thirty-seven with the earliest eighteen and the latest
      more than 70 days. Although the most common presentation was vaginal bleeding or
      abdominal pain, more than 21% was found by ultrasound and rare individuals even
      presented with gastrointestinal symptom which may imply ruptured EP and
      hemorrhagic shock. Giving proper treatment (surgery or local drug injection), the
      majority of them had a successful intrauterine pregnancy with only seven
      miscarried. CONCLUSIONS: Ovulation induction or embryo transfer increased the
      risk of HP greatly and clinician should raise high suspicious during the whole
      first trimester. Although the most ectopic site was ampullary, other sites such
      as cornual, cervical, abdominal especially interstitial or tubal stumps should
      also be assessed by ultrasound even in patients with bilateral salpingectomy or
      tubal obstructed. Repeated ultrasound tests 2 weeks after the diagnosis of
      intrauterine pregnancy with heart beating was very necessary to find the missed
      ones in suspicious patients. Compared with surgery, embryo suction with or
      without proper local drug injection would be more advisable for patients with
      cervical, cornual, or interstitial pregnancy in order to reserve the intrauterine
      pregnancy.

PMID- 29661237
TI  - Evaluating the effects of delivering integrated kinesthetic and tactile cues to
      individuals with unilateral hemiparetic stroke during overground walking.
AB  - BACKGROUND: Integration of kinesthetic and tactile cues for application to post
      stroke gait rehabilitation is a novel concept which needs to be explored. The
      combined provision of haptic cues may result in collective improvement of gait
      parameters such as symmetry, balance and muscle activation patterns. Our proposed
      integrated cue system can offer a cost-effective and voluntary gait training
      experience for rehabilitation of subjects with unilateral hemiparetic stroke.
      METHODS: Ten post-stroke ambulatory subjects participated in a 10 m walking trial
      while utilizing the haptic cues (either alone or integrated application), at
      their preferred and increased gait speeds. In the system a haptic cane device
      (HCD) provided kinesthetic perception and a vibrotactile feedback device (VFD)
      provided tactile cue on the paretic leg for gait modification. Balance, gait
      symmetry and muscle activity were analyzed to identify the benefits of utilizing
      the proposed system. RESULTS: When using kinesthetic cues, either alone or
      integrated with a tactile cue, an increase in the percentage of non-paretic peak
      activity in the paretic muscles was observed at the preferred gait speed (vastus
      medialis obliquus: p <  0.001, partial eta squared (eta2) = 0.954; semitendinosus
      p <  0.001, partial eta2 = 0.793) and increased gait speeds (vastus medialis
      obliquus: p <  0.001, partial eta2 = 0.881; semitendinosus p = 0.028, partial
      eta2 = 0.399). While using HCD and VFD (individual and integrated applications),
      subjects could walk at their preferred and increased gait speeds without
      disrupting trunk balance in the mediolateral direction. The temporal stance
      symmetry ratio was improved when using tactile cues, either alone or integrated
      with a kinesthetic cue, at their preferred gait speed (p <  0.001, partial eta2 =
      0.702). CONCLUSIONS: When combining haptic cues, the subjects walked at their
      preferred gait speed with increased temporal stance symmetry and paretic muscle
      activity affecting their balance. Similar improvements were observed at higher
      gait speeds. The efficacy of the proposed system is influenced by gait speed.
      Improvements were observed at a 20% increased gait speed, whereas, a plateau
      effect was observed at a 40% increased gait speed. These results imply that
      integration of haptic cues may benefit post-stroke gait rehabilitation by
      inducing simultaneous improvements in gait symmetry and muscle activity.

PMID- 29661238
TI  - EP3 (prostaglandin E2 receptor 3) expression is a prognostic factor for
      progression-free and overall survival in sporadic breast cancer.
AB  - BACKGROUND: In various cancers, overexpression of cyclooxygenase (COX)-2 and
      elevated prostaglandin (PG) E2 synthesis have been associated with tumor
      development and progression. The potential of COX-2 inhibitors in cancer
      prevention and treatment has been shown repeatedly; however, their clinical use
      is limited due to toxicity. PGE2 signals via EP receptors 1-4, whose functions
      are analyzed in current research in search for targeted anti-PG therapies. EP2
      and EP4 rather promote tumorigenesis, while the role of EP3, especially in breast
      cancer, is not yet clear and both pro- and anti-tumorigenic effects have been
      described. Our study evaluates EP3 receptor expression in sporadic breast cancer
      and its association with clinicopathological parameters, progression-free and
      overall survival. METHODS: Two hundred eighty-nine sporadic breast cancer samples
      without primary distant metastasis were immunohistochemically analyzed for EP3
      receptor expression. Tissue was stained with primary anti-EP3-antibodies.
      Immunoreactivity was quantified by the immunoreactivity-score (IRS); samples with
      an IRS >= 2 scored as EP3 positive. Chi-squared and Mann-Whitney-U test were used
      for comparison of data; Kaplan-Meier estimates and Cox-regression were used for
      survival analyses. RESULTS: EP3 receptor was expressed in 205 of 289 samples
      analyzed (70.9%). EP3 receptor expression was not associated with
      clinicopathological parameters (e. g. tumor size, hormone receptors, lymph node
      status). Kaplan-Meier estimates showed a significant association of EP3
      positivity with improved progression-free survival (p = 0.002) and improved
      overall survival (p = 0.001) after up to 10 years. Cox regression analysis
      confirmed EP3 positivity as a significant prognostic factor even when other known
      prognosticators were accounted for. CONCLUSIONS: In sporadic breast cancer, EP3
      receptor expression is not significantly associated with clinicopathological
      parameters but is a significant prognostic factor for improved progression-free
      and overall survival. However, the functional aspects of EP3 receptor in breast
      cancer and the way how EP3 may oppose the pro-tumorigenic effects of PGE2
      elevation and COX-2 overexpression are not fully understood so far. Further
      studies aiming at identification of the factors regulated by EP3 are necessary to
      evaluate the possibility of targeting EP3 in future anti-tumor therapy in breast
      cancer.

PMID- 29661239
TI  - Neonatal care practices in sub-Saharan Africa: a systematic review of
      quantitative and qualitative data.
AB  - BACKGROUND: Recommended immediate newborn care practices include thermal care
      (immediate drying and wrapping, skin-to-skin contact after delivery, delayed
      bathing), hygienic cord care and early initiation of breastfeeding. This paper
      systematically reviews quantitative and qualitative data from sub-Saharan Africa
      on the prevalence of key immediate newborn care practices and the factors that
      influence them. METHODS: Studies were identified by searching relevant databases
      and websites, contacting national and international academics and implementers
      and hand-searching reference lists of included articles. English-language
      published and unpublished literature reporting primary data from sub-Saharan
      Africa (published between January 2001 and May 2014) were included if it met the
      quality criteria. Quantitative prevalence data were extracted and summarized.
      Qualitative data were synthesized through thematic analysis, with deductive
      coding used to identify emergent themes within each care practice. A framework
      approach was used to identify prominent and divergent themes. RESULTS: Forty-two
      studies were included as well as DHS data - only available for early
      breastfeeding practices from 33 countries. Results found variation in the
      prevalence of immediate newborn care practices between countries, with the
      exception of skin-to-skin contact after delivery which was universally low. The
      importance of keeping newborn babies warm was well recognized, although thermal
      care practices were sub-optimal. Similar factors influenced practices across
      countries, including delayed drying and wrapping because the birth attendant
      focused on the mother; bathing newborns soon after delivery to remove the dirt
      and blood; negative beliefs about the vernix; applying substances to the cord to
      make it drop off quickly; and delayed breastfeeding because of a perception of a
      lack of milk or because the baby needs to sleep after delivery or does not
      showing signs of hunger. CONCLUSION: The majority of studies included in this
      review came from five countries (Ethiopia, Ghana, Malawi, Tanzania and Uganda).
      There is a need for more research from a wider geographical area, more research
      on newborn care practices at health facilities and standardization in measuring
      newborn care practices. The findings of this study could inform behaviour change
      interventions to improve the uptake of immediate newborn care practices.

PMID- 29661240
TI  - Access factors linked to maternal deaths in Lundazi district, Eastern Province of
      Zambia: a case control study analysing maternal death reviews.
AB  - BACKGROUND: Access factors associated with maternal death are important to
      understand because they are considered to be an essential measure of women's
      health and indicative of the performance of health care systems in any community
      globally. This study aimed to analyse the access risk factors linked to maternal
      deaths in Lundazi district of the Eastern Province of Zambia using secondary data
      obtained from maternal death reviews and delivery registers. METHODS: This was a
      case-control study with cases being recorded maternal deaths for Lundazi district
      (n = 100) while controls were randomly selected Lundazi District Hospital
      deliveries (n = 300) for the period 2010 to 2015. STATATM (Stata Corporation,
      Texas, TX, USA) version 12.0 was used to analyse data. Odds ratio and 95%
      confidence intervals with associated p-values were used to analyse disparities
      between cases and controls while bivariate and multivariate regression analyses
      were done to show associations. RESULTS: The likelihood of experiencing maternal
      death was 94% less among women who completed their scheduled antenatal care
      visits than those who did not (OR 0.06, 95% CI = 0.01-0.27, p = < 0.001). Delayed
      referral associated with maternal deaths and complications were 30% (30) for
      cases, 12% (37) for controls and 17% (67) for both cases and controls. Long
      distances, unskilled deliveries were 3%, (15) for both cases and controls with
      13% (13) for cases and 1% (2) for controls only. CONCLUSION: Antenatal care is
      important in screening for pre-existing risk conditions as well as complications
      in early stages of pregnancy that could impact adversely during pregnancy and
      childbirth. Delay in seeking health care during pregnancy could be minimised if
      health services are brought closer to the communities to reduce on distances
      covered by pregnant women in Lundazi. Maternal education appears to influence
      antenatal health care utilisation because greater knowledge and understanding of
      the importance of antenatal care might increase the ability to select most
      appropriate service. Therefore, there is need for Lundazi District Health Office
      to scale up interventions that motivate women to make at least four scheduled
      antenatal care visits during pregnancy as recommended by the World Health
      Organization.

PMID- 29661241
TI  - Breaking bad habits by improving executive function in individuals with obesity.
AB  - BACKGROUND: Two primary factors that contribute to obesity are unhealthy eating
      and sedentary behavior. These behaviors are particularly difficult to change in
      the long-term because they are often enacted habitually. Cognitive Remediation
      Therapy has been modified and applied to the treatment of obesity (CRT-O) with
      preliminary results of a randomized controlled trial demonstrating significant
      weight loss and improvements in executive function. The objective of this study
      was to conduct a secondary data analysis of the CRT-O trial to evaluate whether
      CRT-O reduces unhealthy habits that contribute to obesity via improvements in
      executive function. METHOD: Eighty participants with obesity were randomized to
      CRT-O or control. Measures of executive function (Wisconsin Card Sort Task and
      Trail Making Task) and unhealthy eating and sedentary behavior habits were
      administered at baseline, post-intervention and at 3 month follow-up. RESULTS:
      Participants receiving CRT-O demonstrated improvements in both measures of
      executive function and reductions in both unhealthy habit outcomes compared to
      control. Mediation analyses revealed that change in one element of executive
      function performance (Wisconsin Card Sort Task perseverance errors) mediated the
      effect of CRT-O on changes in both habit outcomes. CONCLUSION: These results
      suggest that the effectiveness of CRT-O may result from the disruption of
      unhealthy habits made possible by improvements in executive function. In
      particular, it appears that cognitive flexibility, as measured by the Wisconsin
      Card Sort task, is a key mechanism in this process. Improving cognitive
      flexibility may enable individuals to capitalise on interruptions in unhealthy
      habits by adjusting their behavior in line with their weight loss goals rather
      than persisting with an unhealthy choice. TRIAL REGISTRATION: The RCT was
      registered with the Australian New Zealand Registry of Clinical Trials (trial id:
      ACTRN12613000537752 ).

PMID- 29661242
TI  - Use, applicability and reliability of depth of hypnosis monitors in children - a
      survey among members of the European Society for Paediatric Anaesthesiology.
AB  - BACKGROUND: To assess the thoughts of practicing anaesthesiologists about the use
      of depth of hypnosis monitors in children. METHODS: Members of the European
      Society for Paediatric Anaesthesiology were invited to participate in an online
      survey about their thoughts regarding the use, applicability and reliability of
      hypnosis monitoring in children. RESULTS: The survey achieved a response rate of
      30% (N = 168). A total of 138 completed surveys were included for further
      analysis. Sixty-eight respondents used hypnosis monitoring in children (Users)
      and 70 did not (Non-users). Sixty-five percent of the Users reported prevention
      of intra-operative awareness as their main reason to apply hypnosis monitoring.
      Among the Non-users, the most frequently given reason (43%) not to use hypnosis
      monitoring in children was the perceived lack or reliability of the devices in
      children. Hypnosis monitoring is used with a higher frequency during propofol
      anaesthesia than during inhalation anaesthesia. Hypnosis monitoring is
      furthermore used more frequently in children > 4 years than in younger children.
      An ideal hypnosis monitor should be reliable for all age groups and any
      (combination of) anaesthetic drug. We found no agreement in the interpretation of
      monitor index values and subsequent anaesthetic interventions following from it.
      CONCLUSIONS: Prevention of intraoperative awareness appears to be the most
      important reason to use hypnosis monitoring in children. The perceived lack of
      reliability of hypnosis monitoring in children is the most important reasons not
      to use it. No consensus currently exists on how to adjust anaesthesia according
      to hypnosis monitor index values in children.

PMID- 29661243
TI  - Effect of neoadjuvant chemotherapy regimen on relapse-free survival among
      patients with breast cancer achieving a pathologic complete response: an early
      step in the de-escalation of neoadjuvant chemotherapy.
AB  - BACKGROUND: Patients with breast cancer who have a pathologic complete response
      (pCR) to neoadjuvant chemotherapy (NACT) have improved survival. We hypothesize
      that once pCR has been achieved, there is no difference in subsequent
      postsurgical recurrence-free survival (RFS), whichever NACT regimen is used.
      METHODS: Data from patients with breast cancer who achieved pCR after NACT
      between 1996 and 2011 were reviewed. RFS was estimated by the Kaplan-Meier
      method, and differences between groups were assessed using log-rank testing. Cox
      proportional hazards regression analysis adjusted for age, menopausal status,
      stage, grade, tumor subtype, and adjuvant endocrine HER2-targeted radiation
      treatment. RESULTS: Among 721 patients who achieved pCR after NACT, 157 (21.8%)
      were hormone receptor-positive (HR), 310 (43.3%) were HER2-amplified, and 236
      (32.7%) were triple-negative; 292 (40.5%) were stage IIA, 153 (21.2%) were stage
      IIB, 78 (10.8%) were stage IIIA, 66 (9.2%) were stage IIIB, and 132 (18.3%) were
      stage IIIC. Most patients (367 [50.9%]) had been treated with adriamycin-based
      chemotherapy plus taxane (A + T), 56 (7.8%) without taxane (A no T), 227 (31.5%)
      with HER2-targeted therapy, and 71 (9.8%) provider choice. Median follow-up was
      7.1 years. Adjuvant chemotherapy was employed in 196 (27%) patients, adjuvant
      endocrine in 261 (36%), and adjuvant radiation in the majority (559 [77.5%]).
      There was no statistically significant difference in RFS by NACT group. Adjusted
      RFS hazard ratios, comparing each treatment with the reference group A + T, were
      1.25 (95% CI 0.47-3.35) for A no T, 0.90 (95% CI 0.37-2.20) for HER2-targeted
      therapy, and 1.28 (95% CI 0.55-2.98) for provider choice. CONCLUSIONS: These data
      suggest that postsurgical RFS is not significantly influenced by the choice of
      NACT or cancer subtype among patients achieving pCR.

PMID- 29661244
TI  - Surgical management of ascending aortic pseudoaneurysm in a 2-year-old boy: a
      case report.
AB  - BACKGROUND: Aortic pseudoaneurysms are rare but life-threatening complications
      usually seen after cardiac surgery. The causes could be multifactorial such as
      infection or trauma. CASE PRESENTATION: We report the surgical management of a
      postoperative pseudoaneurysm of the ascending aorta caused by methicillin
      resistant Staphylococcus aureus in a 2-year-old Middle Eastern boy who had
      undergone ventricular septal defect closure, subaortic membrane resection, and
      pulmonary artery de-banding. He was immediately operated on for resection of the
      aneurysm. A computed tomography scan at 2 months following surgery showed no
      aneurysm. Antibiotics were continued for 6 weeks and our patient was discharged
      with negative blood cultures. CONCLUSION: Early diagnosis and appropriate
      treatment of such rare complication can be lifesaving.

PMID- 29661245
TI  - Socioeconomic health inequality in malaria indicators in rural western Kenya:
      evidence from a household malaria survey on burden and care-seeking behaviour.
AB  - BACKGROUND: Health inequality is a recognized barrier to achieving health-related
      development goals. Health-equality data are essential for evidence-based planning
      and assessing the effectiveness of initiatives to promote equity. Such data have
      been captured but have not always been analysed or used to manage programming.
      Health data were examined for microeconomic differences in malaria indices and
      associated malaria control initiatives in western Kenya. METHODS: Data was
      analysed from a malaria cross-sectional survey conducted in July 2012 among 2719
      people in 1063 households in Siaya County, Kenya. Demographic factors, history of
      fever, malaria parasitaemia, malaria medication usage, insecticide-treated net
      (ITN) use and expenditure on malaria medications were collected. A composite
      socioeconomic status score was created using multiple correspondence analyses
      (MCA) of household assets; households were classified into wealth quintiles and
      dichotomized into poorest (lowest 3 quintiles; 60%) or less-poor (highest 2
      quintiles; 40%). Prevalence rates were calculated using generalized linear
      modelling. RESULTS: Overall prevalence of malaria infection was 34.1%, with
      significantly higher prevalence in the poorest compared to less-poor households
      (37.5% versus 29.2%, adjusted prevalence ratio [aPR] 1.23; 95% CI = 1.08-1.41, p
      = 0.002). Care seeking (aPR = 0.95; 95% CI 0.87-1.04, p = 0.229), medication use
      (aPR = 0.94; 95% CI 0.87-1.00, p = 0.087) and ITN use (aPR = 0.96; 95% CI = 0.87
      1.05, p = 0.397) were similar between households. Among all persons surveyed,
      36.4% reported taking malaria medicines in the prior 2 weeks; 92% took artemether
      lumefantrine, the recommended first-line malaria medication. In the poorest
      households, 4.9% used non-recommended medicines compared to 3.5% in less-poor (p
      = 0.332). Mean and standard deviation [SD] for expenditure on all malaria
      medications per person was US$0.38 [US$0.50]; the mean was US$0.35 [US$0.52]
      amongst the poorest households and US$0.40 [US$0.55] in less-poor households (p =
      0.076). Expenditure on non-recommended malaria medicine was significantly higher
      in the poorest (mean US$1.36 [US$0.91]) compared to less-poor households (mean
      US$0.98 [US$0.80]; p = 0.039). CONCLUSIONS: Inequalities in malaria infection and
      expenditures on potentially ineffective malaria medication between the poorest
      and less-poor households were evident in rural western Kenya. Findings highlight
      the benefits of using MCA to assess and monitor the health-equity impact of
      malaria prevention and control efforts at the microeconomic level.

PMID- 29661247
TI  - Informing implementation of quality improvement in Australian primary care.
AB  - BACKGROUND: Quality Improvement (QI) initiatives in primary care are effective at
      improving uptake of evidence based guidelines, but are difficult to implement and
      sustain. In Australia meso-level health organisations such as Primary health care
      Organisations (PHCO) offer new opportunities to implement area-wide QI programs.
      This study sought to identify enablers and barriers to implementation of an
      existing Australian QI program and to identify strategic directions that PHCOs
      can use in the ongoing development of QI in this environment. METHODS: Semi
      structured telephone interviews were conducted with 15 purposively selected
      program staff and participants from the Australian Primary Care Collaborative
      (APCC) QI program. Interviewees included seven people involved in design,
      administration and implementation of the APCC program and eight primary care
      providers (seven General Practitioners (GPs) and one practice nurse) who had
      participated in the program from 2004 to 2014. Interviewees were asked to
      describe their experience of the program and reflect on what enabled or impeded
      its implementation. Interviews were recorded, transcribed and iteratively
      analysed, with early analysis informing subsequent interviews. Identified themes
      and their implications were reviewed by a GP expert reference group. RESULTS:
      Implementation enablers and barriers were grouped into five thematic areas: (1)
      leadership, particularly the identification and utilisation of change champions;
      (2) organisational culture that supports quality improvement; (3) funding
      incentives that support a culture of quality and innovation; (4) access to and
      use of accurate data; and 5) design and utilisation of clinical systems that
      enable and support these issues. In all of these areas, the active involvement of
      an overarching external support organisation was considered a key ingredient to
      successful implementation. CONCLUSION: There are substantial opportunities for
      PHCOs to play a pivotal role in QI implementation in Australia and
      internationally. In developing QI programs and policies, such organisations ought
      to invest their efforts in: (1) identifying and mentoring local leaders; (2)
      fostering QI culture via development of local peer networks; (3) developing and
      advocating for alternative funding models to support and incentivise these
      activities; (4) investing in data and audit tool infrastructure; and (5)
      facilitation of systems implementation within primary care practices.

PMID- 29661246
TI  - Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance
      mutations in historic UK data.
AB  - BACKGROUND: The prevalence of HIV-1 resistance to antiretroviral therapies (ART)
      has declined in high-income countries over recent years, but drug resistance
      remains a substantial concern in many low and middle-income countries. The Q151M
      and T69 insertion (T69i) resistance mutations in the viral reverse transcriptase
      gene can reduce susceptibility to all nucleoside/tide analogue reverse
      transcriptase inhibitors, motivating the present study to investigate the risk
      factors and outcomes associated with these mutations. METHODS: We considered all
      data in the UK HIV Drug Resistance Database for blood samples obtained in the
      period 1997-2014. Where available, treatment history and patient outcomes were
      obtained through linkage to the UK Collaborative HIV Cohort study. A matched case
      control approach was used to assess risk factors associated with the appearance
      of each of the mutations in ART-experienced patients, and survival analysis was
      used to investigate factors associated with viral suppression. A further analysis
      using matched controls was performed to investigate the impact of each mutation
      on survival. RESULTS: A total of 180 patients with Q151M mutation and 85 with
      T69i mutation were identified, almost entirely from before 2006. Occurrence of
      both the Q151M and T69i mutations was strongly associated with cumulative period
      of virological failure while on ART, and for Q151M there was a particular
      positive association with use of stavudine and negative association with use of
      boosted-protease inhibitors. Subsequent viral suppression was negatively
      associated with viral load at sequencing for both mutations, and for Q151M we
      found a negative association with didanosine use but a positive association with
      boosted-protease inhibitor use. The results obtained in these analyses were also
      consistent with potentially large associations with other drugs. Analyses were
      inconclusive regarding associations between the mutations and mortality, but
      mortality was high for patients with low CD4 at detection. CONCLUSIONS: The Q151M
      and T69i resistance mutations are now very rare in the UK. Our results suggest
      that good outcomes are possible for people with these mutations. However, in this
      historic sample, viral load and CD4 at detection were important factors in
      determining prognosis.

PMID- 29661249
TI  - Using qualitative and community-based engagement approaches to gain access and to
      develop a culturally appropriate STI prevention intervention for foreign female
      entertainment workers in Singapore.
AB  - BACKGROUND: There is an increasing global movement of foreign female
      entertainment workers (FEWs), a hard-to-reach population vulnerable to HIV/STIs.
      This paper described the needs assessment phase before intervention
      implementation where the socio-organisation, sexual risk behaviours and access to
      health services of foreign FEWs in Singapore were explored. We also highlighted
      how qualitative inquiry, census enumeration technique and community-based
      engagement approaches were used to gain access and to develop a culturally
      appropriate STI prevention intervention. METHODS: In-depth interviews,
      observations, informal conversational interviews, mystery client and critical
      incident technique were used. We estimated the size of FEW population using the
      census enumeration technique. The findings were used to inform intervention
      development and implementation. RESULTS: We estimated 376 Vietnamese and 330 Thai
      FEWs in 2 geographical sites where they operated in Singapore. Their reasons for
      non-condom use included misconceptions on the transmission and consequences of
      STI/HIV, low risk perception of contracting HIV/STI from paid/casual partner,
      lack of skills to negotiate or to persuade partner to use condom, unavailability
      of condoms in entertainment establishments and fear of the police using condom as
      circumstantial evidence. They faced difficulties in accessing health services due
      to fear of identity exposure, stigmatisation, cost and language differences. To
      develop the intervention, we involved FEWs and peer educators, and ensured that
      the intervention was non-stigmatising and met their needs. To foster their
      participation, we used culturally-responsive recruitment strategies, and ensured
      that the trial was anonymous and acceptable to the FEWs. These strategies were
      effective as we achieved a participation rate of 90.3%, a follow-up rate of 70.5%
      for the comparison and 66.8% for the intervention group. The interventions group
      reported a significant increase in consistent condom use with a reduction in STI
      incidence compared to no significant change in the comparison group. CONCLUSIONS:
      The qualitative inquiry approaches to gain access, to foster participation and to
      develop a culturally appropriate intervention, along with the census enumeration
      technique application to estimate the FEW population sizes has led to successful
      intervention implementation as well as safer sexual behaviour and STI incidence
      reduction. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02780986 . Registered 23
      May 2016 (retrospectively registered).

PMID- 29661248
TI  - The regulation of combined treatment-induced cell death with recombinant TRAIL
      and bortezomib through TRAIL signaling in TRAIL-resistant cells.
AB  - BACKGROUND: Multiple trials have attempted to demonstrate the effective induction
      of cell death in TRAIL-resistant cancer cells, including using a combined
      treatment of recombinant TRAIL and various proteasome inhibitors. These studies
      have yielded limited success, as the mechanism of cell death is currently
      unidentified. Understanding this mechanism's driving forces may facilitate the
      induction of cell death in TRAIL-resistant cancer cells. METHODS: Three kinds of
      recombinant soluble TRAIL proteins were treated into TRAIL-resistant cells and
      TRAIL-susceptible cells, with or without bortezomib, to compare their respective
      abilities to induce cell death. Recombinant TRAIL was treated with bortezomib to
      investigate whether this combination treatment could induce tumor regression in a
      mouse syngeneic tumor model. To understand the mechanism of combined treatment
      induced cell death, cells were analyzed by flow cytometry and the effects of
      various cell death inhibitors on cell death rates were examined. RESULTS:
      ILz:rhTRAIL, a recombinant human TRAIL containing isoleucine zipper
      hexamerization domain, showed the highest cell death inducing ability both in
      single treatment and in combination treatment with bortezomib. In both TRAIL
      resistant and TRAIL-susceptible cells treated with the combination treatment, an
      increase in cell death rates was dependent upon both the dose of TRAIL and its
      intrinsic properties. When a syngeneic mouse tumor model was treated with the
      combination of ILz:rhTRAIL and bortezomib, significant tumor regression was seen
      as a result of the effective induction of cancer cell death. The combination
      treatment-induced cell death was both inhibited by TRAIL blocking antibody and
      caspase-dependent. However, it was not inhibited by various ER stress inhibitors
      and autophagy inhibitors. CONCLUSIONS: The combination treatment with ILz:rhTRAIL
      and bortezomib was able to induce cell death in both TRAIL-susceptible and TRAIL
      resistant cancer cells through the intracellular TRAIL signaling pathway. The
      efficiency of cell death was dependent on the properties of TRAIL under the
      environment provided by bortezomib. The combination treatment-induced cell death
      was not regulated by bortezomib-induced ER stress response or by autophagy.

PMID- 29661250
TI  - Isocitrate dehydrogenase 1-snail axis dysfunction significantly correlates with
      breast cancer prognosis and regulates cell invasion ability.
AB  - BACKGROUND: The isocitrate dehydrogenase (IDH) gene family expresses key
      functional metabolic enzymes in the Krebs cycle and mediates the epigenetic
      reprogramming, which serves as an important biomarker of breast cancer. However,
      the expression levels of the IDH protein and their biological function in human
      breast cancer remain largely unknown. METHODS: In this study, the clinical impact
      of IDH1 expression on the progression and prognosis of breast cancer was
      evaluated using immunohistochemistry assay (IHC) of the corresponding tumor
      adjacent normal, ductal carcinoma in situ (DCIS), and invasive ductal carcinoma
      (IDC) tissues from 309 patients with breast ductal carcinoma. The relationship
      between microRNA (miRNA) and IDH1 were examined by a bioinformatics approach,
      western blot and reporter assay. The biological functions of IDH1 were examined
      in breast cancer cells with IDH1 knockdown, including proliferation, migration
      and invasion. RESULTS: The present findings revealed that the mRNA and protein
      expression levels of IDH1 were both significantly lower in breast cancer tissues
      than in adjacent normal tissues. A low expression level of IDH1 in breast cancer
      significantly correlated with advanced stage (p = 0.012), lymph node metastasis
      (p = 0.018), and poor disease-specific survival (DSS) (adjusted hazard ratio
      (AHR), 1.57, 95% confidence interval (CI), 1.08-2.30; p = 0.02). Furthermore,
      oncogenic miR-32 and miR-92b were identified to suppress IDH1 expression, leading
      to the inhibition of cell migration and invasion. We further explored whether
      reduced expression of IDH1 significantly increases snail expression by activating
      HIFalpha (hypoxia-inducible factor-1 alpha) and NFkappaB (nuclear factor kappa B)
      signaling. Multivariate Cox regression analysis revealed that the combination of
      low IDH1 and high snail expression could be an independent risk factor for
      shorter DSS (AHR, 2.34; 95% CI, 1.32-4.16; p = 0.004) and shorter disease-free
      survival (AHR, 2.50; 95% CI, 1.39-4.50; p = 0.002) in patients with breast
      cancer. CONCLUSION: Our findings revealed that a IDH1low/Snailhigh molecular
      signature could serve as an independent biomarker for poor prognosis in breast
      cancer.

PMID- 29661251
TI  - Under diagnosis of intestinal schistosomiasis in a referral hospital, North
      Ethiopia.
AB  - OBJECTIVE: The present cross-sectional study was aimed at determining the
      magnitude of under diagnosis of intestinal schistosomiasis among patients
      requested for routine ova/parasite examination at Ayder referral hospital.
      RESULTS: A total of 280 stool samples were collected and only 5% of the patients
      were positive for ova of Schistosoma mansoni in the routine direct wet mount
      microscopy. On the other hand, 12.5% of the patients were positive for ova
      Schistosoma mansoni when the stool samples were processed by either Kato Kat or
      formol ether concentration techniques. Moderate test agreement (kappa = 0.48) was
      recorded for wet mount. Formol-ether concentration (kappa = 0.89) and Kato-Katz
      (kappa = 0.92) showed excellent agreements with the 'Gold' standard. Direct wet
      mount technique exhibited the poorest sensitivity (35%) of detection of ova of
      Schistosoma mansoni. Hence, the Kato-Katz technique should be implemented in
      parallel with the direct wet mount microscopy for Schistosoma mansoni presumptive
      patients.

PMID- 29661253
TI  - Activity-dependent decrease in contact areas between subsurface cisterns and
      plasma membrane of hippocampal neurons.
AB  - Subsurface cistern (SSC) in neuronal soma and primary dendrites is a specialized
      compartment of endoplasmic reticulum (ER) that is in close apposition (10 nm)
      with the plasma membrane (PM). ER-PM contact areas are thought to be involved in
      intracellular calcium regulation. Here, structural changes of SSC in hippocampal
      neurons were examined by electron microscopy upon depolarization with high K+ (90
      mM) or application of NMDA (50 MUM) in rat dissociated cultures as well as
      organotypic slice cultures. The number and average length of SSC-PM contact areas
      in neuronal somas significantly decreased within 30 s under excitatory condition.
      This decrease in SSC-PM contact area progressed with time and was reversible.
      These results demonstrate a structural decoupling between the SSC and the PM upon
      stimulation, suggesting that there may be a functional decoupling of the calcium
      regulation. Because SSC-PM contact areas may mediate calcium influx, the decrease
      in contact area may protect neurons from calcium overload upon heightened
      stimulation.

PMID- 29661252
TI  - miR-148b-3p functions as a tumor suppressor in GISTs by directly targeting KIT.
AB  - BACKGROUND: Gain-of-function mutations and overexpression of KIT are
      characteristic features of gastrointestinal stromal tumor (GIST). Dysregulation
      in miRNA expression may lead to KIT overexpression and tumorigenesis. METHODS:
      miRNA microarray analysis and real-time PCR were used to determine the miRNA
      expression profiles in a cohort of 69 clinical samples including 50
      CD117IHC+/KITmutation GISTs and 19 CD117IHC-/wild-type GISTs. GO enrichment and
      KEGG pathway analyses were performed to reveal the predicted targets of the
      dysregulated miRNAs. Of the dysregulated miRNAs whose expression was inversely
      correlated with that of KIT miRNAs were predicted by bioinformatics analysis and
      confirmed by luciferase reporter assay. Cell counting kit-8 (CCK-8) and flow
      cytometry were used to measure the cell proliferation, cycle arrest and
      apoptosis. Wound healing and transwell assays were used to evaluate migration and
      invasion. A xenograft BALB/c nude mouse model was applied to investigate the
      tumorigenesis in vivo. Western blot and qRT-PCR were used to investigate the
      protein and mRNA levels of KIT and its downstream effectors including ERK, AKT
      and STAT3. RESULTS: Of the six miRNAs whose expression was inversely correlated
      with that of KIT, we found that miR-148b-3p was significantly downregulated in
      the CD117IHC+/KITmutation GIST cohort. This miRNA was subsequently found to
      inhibit proliferation, migration and invasion of GIST882 cells. Mechanistically,
      miR-148b-3p was shown to regulate KIT expression through directly binding to the
      3'-UTR of the KIT mRNA. Restoration of miR-148b-3p expression in GIST882 cells
      led to reduced expression of KIT and the downstream effectors proteins ERK, AKT
      and STAT3. However, overexpression of KIT reversed the inhibitory effect of miR
      148b-3p on cell proliferation, migration and invasion. Furthermore, we found that
      reduced miR-148b-3p expression correlated with poor overall survival (OS) and
      disease-free survival (DFS) in GIST patients. CONCLUSION: miR-148b-3p functions
      as an important regulator of KIT expression and a potential prognostic biomarker
      for GISTs.

PMID- 29661254
TI  - The risk and predictors for severe radiation pneumonitis in lung cancer patients
      treated with thoracic reirradiation.
AB  - BACKGROUND: Thoracic reirradiation (re-RT) is increasingly administered. However,
      radiation pneumonitis (RP) remains to be the most common side effect from
      retreatment. This study aimed to determine the risk and predictors for severe RP
      in patients receiving thoracic re-RT. METHODS: Sixty seven patients with lung
      cancer received thoracic re-RT for recurrent or metastatic disease. Three
      dimensional conformal radiotherapy (3D-CRT)/intensity modulated radiotherapy
      (IMRT) was used for 60 patients, and stereotactic body radiation therapy (SBRT)
      was used in 7 patients. Deformable image registration (DIR) was performed to
      create a composite plan. Severe (grade >= 3) RP was graded according to Common
      Terminology Criteria for Adverse Events version 4.0. RESULTS: Eighteen patients
      (26.9%) developed grade >= 3 RP (17 of grade 3, and 1 of grade 4). In univariate
      analyses, V5 and mean lung dose (MLD) of initial RT or re-RT plans, V5 and V20 of
      composite plans, and the overlap between V5 of initial RT and V5 of re-RT
      plans/V5 of re-RT plans (overlap-V5/re-V5) were significantly associated with
      grade >= 3 RP (P < 0.05 for each comparison). Multivariate analysis revealed that
      MLD of the initial RT plans (HR = 14.515, 95%CI:1.778-118.494, P = 0.013), V5 of
      the composite plans (HR = 7.398, 95%CI:1.319-41.495, P = 0.023), and overlap
      V5/re-V5 (P = 0.041) were independent predictors for grade >= 3 RP. Out-of-field
      failures with medium overlap-V5/re-V5 of 0.4-0.8 was associated with higher risk
      of grade >= 3 RP compared with in-field failures (18.3% vs. 50%, P = 0.014).
      CONCLUSIONS: The risk of grade >= 3 RP could be predicted not only by dose-volume
      variables from re-RT plan, but also by some from initial-RT and composite plans.
      Out-of-field failures was associated with higher risk of severe RP compared with
      in-field failures in some cases.

PMID- 29661256
TI  - Main effects of human saliva on flavour perception and the potential contribution
      to food consumption.
AB  - Whole saliva is a mixture composed by the secretions of the major and minor
      salivary glands and the crevicular fluid, bacteria, cells and food debris. Its
      properties (flow and composition) are highly intra- and inter-individually
      dependent and reflect the health status of individuals. Saliva plays a key role
      in the eating process and on the perception of flavour. Flavour corresponds to
      the combined effect of taste sensations, aromatics and chemical feeling factors
      evoked by food in the oral cavity. It is a key determinant of food consumption
      and intake. This review summarises the evidence about the role of saliva in
      flavour perception and its potential contribution to food intake. All in all,
      evidence on the relationships between salivary parameters and both food
      perception and feeding behaviour is presented. This review emphasises that new
      studies accounting for the effect of salivary constituents on flavour alterations
      due to diseases (i.e. cancer, obesity and diabetes) are lacking and are expected
      in the incoming years.

PMID- 29661257
TI  - Comparison of parasite loads in serum and blood samples from patients in acute
      and chronic phases of Chagas disease.
AB  - Molecular methods have been developed for the detection and quantification of
      Trypanosoma cruzi DNA in blood samples from patients with Chagas disease.
      However, aspects of sample processing necessary for quantitative real-time PCR
      (qPCR), such as the addition of guanidine hydrochloride to whole blood samples,
      may limit timely access to molecular diagnosis. We analysed 169 samples from
      serum and guanidine-EDTA blood (GEB) obtained from patients in acute and chronic
      phases of Chagas disease. We applied qPCR targeted to the satellite DNA region.
      Finally, we compared the parasite loads and cycle of threshold values of the
      qPCR. The results confirmed the usefulness of serum samples for the detection and
      quantification of parasite DNA in patients with Chagas disease, especially in the
      acute phase. However, the parasite loads detected in serum samples from patients
      in the chronic phase were lower than those detected in GEB samples. The
      epidemiological implications of the findings are herein discussed.

PMID- 29661258
TI  - Liver metabolism in adult male mice offspring: consequences of a maternal,
      paternal or both maternal and paternal high-fructose diet.
AB  - The study aimed to evaluate the consequences of the consumption of a high
      fructose diet (HFR; fructose was responsible for 45% of the energy from
      carbohydrates) by the mother, the father, or both on C57BL/6 adult male
      offspring. Non-consanguineous parents received the diet (HFR or control, C) from
      8 weeks before mating until weaning (n=10 fathers and n=10 mothers on each diet).
      After weaning, only the C diet was offered to offspring. The groups were formed
      by one male randomly taken from each litter. The offspring groups were identified
      according to the mother's diet (the first letter), then the father's diet (the
      second letter), that is, C/C, C/HFR, HFR/C, HFR/HFR (n=10 per group). The parents
      exhibited the following characteristics: compared with those of the C group, the
      HFR parents had higher blood pressure (BP), enlarged liver, increased hepatic
      triacylglycerol content, hypercholesterolemia, hypertriglyceridemia, high plasma
      leptin and low adiponectin. The offspring exhibited the following
      characteristics: compared with the C/C group, the HFR/HFR group had high BP. The
      C/HFR, HFR/C and HFR/HFR showed elevated uric acid and leptin levels and
      diminished adiponectin. The HFR/HFR group showed liver inflammation (increased
      NFkappaB, SOCS3, JNK, TNF-alpha, IL1-beta and IL6 levels). Likewise, SREBP-1c and
      FAS were upregulated. In conclusion, the consumption of a HFR by the mother
      and/or father is associated with adverse effects on liver metabolism in adult
      male offspring. When both mother and father are fed a HFR, the adverse effects on
      the offspring are more severe.

PMID- 29661255
TI  - Serotonergic gene polymorphisms (5-HTTLPR, 5HTR1A, 5HTR2A), and population
      differences in aggression: traditional (Hadza and Datoga) and industrial
      (Russians) populations compared.
AB  - BACKGROUND: Current knowledge on genetic basis of aggressive behavior is still
      contradictory. This may be due to the fact that the majority of studies targeting
      associations between candidate genes and aggression are conducted on industrial
      societies and mainly dealing with various types of psychopathology and disorders.
      Because of that, our study was carried on healthy adult individuals of both sex
      (n = 853). METHODS: Three populations were examined: two traditional (Hadza and
      Datoga) and one industrial (Russians), and the association of aggression with the
      following polymorphisms 5-HTTLPR, rs6295 (5HTR1A gene), and rs6311 (5HTR2A gene)
      were tested. Aggression was measured as total self-ratings on Buss-Perry
      Aggression Questionnaire. RESULTS: Distributions of allelic frequencies of 5
      HTTLPR and 5HTR1A polymorphisms were significantly different among the three
      populations. Consequently, the association analyses for these two candidate genes
      were carried out separately for each population, while for the 5HTR2A
      polymorphism, it was conducted on the pooled data that made possible to introduce
      ethnic factor in the ANOVA model. The traditional biometrical approach revealed
      no sex differences in total aggression in all three samples. The three-way ANOVA
      (MU + 5-HTTLPR + 5HTR1A + 5HTR2A +epsilon) with measures of self-reported total
      aggression as dependent variable revealed significant effect of the second
      serotonin receptor gene polymorphism for the Hadza sample. For the Datoga, the
      interaction effect between 5-HTTLPR and 5HTR1A was significant. No significant
      effects of the used polymorphisms were obtained for Russians. The results of two
      way ANOVA with ethnicity and the 5HTR2A polymorphism as main effects and their
      interactions revealed the highly significant effect of ethnicity, 5HTR2A
      polymorphism, and their interaction on total aggression. CONCLUSIONS: Our data
      provided obvious confirmation for the necessity to consider the population
      origin, as well as cultural background of tested individuals, while searching for
      associations between genes and behavior, and demonstrated the role of cultural
      attitudes towards the use of in-group aggression. Our data partly explained the
      reasons for disagreement in results of different teams, searching for candidate
      gene associations with behavior without considerations of culturally desirable
      norms. Previous studies suggested that the 5HTR2A gene polymorphism associates
      with aggression and criminality. Our data extended these findings, demonstrating
      the role of rs6311 (5HTR2A gene) in aggression in adult healthy men and women
      from our samples. We found that G-allele carriers were rated higher on total
      aggression.

PMID- 29661259
TI  - Low fertility, fecundity and numbers of mated female offspring explain the lower
      reproductive success of the parasitic mite Varroa destructor in African
      honeybees.
AB  - Although Varroa destructor is the most serious ecto-parasite to the honeybee,
      Apis mellifera L., some honeybee populations such as Apis mellifera scutellata in
      Kenya can survive mite infestations without treatment. Previously, we reported
      that grooming behaviour could be a potential tolerant mechanism expressed by this
      honeybee subspecies towards mite infestation. However, both hygienic and grooming
      behaviours could not explain the lower mite-infestation levels recorded in these
      colonies. Here, we investigated the involvement of other potential resistant
      mechanisms including suppression of mite reproduction in worker brood cells of A.
      m. scutellata to explain the low mite numbers in their colonies. High infertility
      rates (26-27%) and percentages of unmated female offspring (39-58%) as well as
      low fecundity (1.7-2.2, average offspring produced) were identified as key
      parameters that seem to interact with one another during different seasons to
      suppress mite reproduction in A. m. scutellata colonies. We also identified
      offspring mortality in both sexes and absence of male offspring as key factors
      accounting for the low numbers of mated daughter mites produced in A. m.
      scutellata colonies. These results suggest that reduced mite reproductive success
      could explain the slow mite population growth in A. m. scutellata colonies.

PMID- 29661260
TI  - Implementing routine blood-borne virus testing for HCV, HBV and HIV at a London
      Emergency Department - uncovering the iceberg?
AB  - UK guidelines recommend routine HIV testing in high prevalence emergency
      departments (ED) and targeted testing for HBV and HCV. The 'Going Viral' campaign
      implemented opt-out blood-borne virus (BBV) testing in adults in a high
      prevalence ED, to assess seroprevalence, uptake, linkage to care (LTC) rates and
      staff time taken to achieve LTC. Diagnosis status (new/known/unknown), current
      engagement in care, and severity of disease was established. LTC was defined as
      patient informed plus ?1 clinic visit. A total of 6211/24 981 ED attendees were
      tested (uptake 25%); 257 (4.1%) were BBV positive (15 co-infected), 84 (33%)
      required LTC. 100/147 (68%) HCV positives were viraemic; 44 (30%) required LTC
      (13 new, 16 disengaged). 26/54 (48%) HBV required LTC (seven new, 11 disengaged).
      16/71 (23%) HIV required LTC (10 new, five disengaged). 26/84 (31%) patients
      requiring LTC had advanced disease (CD4 1, Fibroscan F3/F4 or liver cancer),
      including five with AIDS-defining conditions and three hepatocellular carcinomas.
      There were five BBV-related deaths. BBV prevalence was high (4.1%); most were HCV
      (2.4%). HIV patients were more successfully and quickly LTC than HBV or HCV
      patients. ED testing was valuable as one-third of those requiring LTC (new,
      disengaged or unknown status patients) had advanced disease.

PMID- 29661261
TI  - Genetic diversity and phylogeography of the elusive, but epidemiologically
      important Echinococcus granulosus sensu stricto genotype G3.
AB  - Cystic echinococcosis (CE) is a severe parasitic disease caused by the species
      complex Echinococcus granulosus sensu lato. Human infections are most commonly
      associated with E. granulosus sensu stricto (s.s.), comprising genotypes G1 and
      G3. The objective of the current study was to provide first insight into the
      genetic diversity and phylogeography of genotype G3. Despite the epidemiological
      importance of the genotype, it has remained poorly explored due to the ambiguity
      in the definition of the genotype. However, it was recently demonstrated that
      long sequences of mitochondrial DNA (mtDNA) provide a reliable method to
      discriminate G1 and G3 from each other. Therefore, we sequenced near-complete
      mtDNA of 39 G3 samples, covering most of the known distribution range and host
      spectra of the genotype. The phylogenetic network revealed high genetic variation
      within E. granulosus s.s. G3 and while G3 is significantly less prevalent
      worldwide than G1, the genetic diversity of both of the genotypes is equally
      high. We also present the results of the Bayesian phylogeographic analysis, which
      yielded several well-supported diffusion routes of genotype G3 originating from
      Turkey and Iran, suggesting the Middle East as the origin of the genotype.

PMID- 29661262
TI  - The genetics and molecular biology of fever-associated seizures or epilepsy.
AB  - Fever-associated seizures or epilepsy (FASE) is primarily characterised by the
      occurrence of a seizure or epilepsy usually accompanied by a fever. It is common
      in infants and children, and generally includes febrile seizures (FS), febrile
      seizures plus (FS+), Dravet syndrome (DS) and genetic epilepsy with febrile
      seizures plus (GEFSP). The aetiology of FASE is unclear. Genetic factors may play
      crucial roles in FASE. Mutations in certain genes may cause a wide spectrum of
      phenotypical overlap ranging from isolated FS, FS+ and GEFSP to DS. Synapse
      associated proteins, postsynaptic GABAA receptor, and sodium channels play
      important roles in synaptic transmission. Mutations in these genes may involve in
      the pathogenesis of FASE. Elevated temperature promotes synaptic vesicle (SV)
      recycling and enlarges SV size, which may enhance synaptic transmission and
      contribute to FASE occurring. This review provides an overview of the loci,
      genes, underlying pathogenesis and the fever-inducing effect of FASE. It may
      provide a more comprehensive understanding of pathogenesis and contribute to the
      clinical diagnosis of FASE.

PMID- 29661263
TI  - A new microsporidium Percutemincola moriokae gen. nov., sp. nov. from Oscheius
      tipulae: A novel model of microsporidia-nematode associations.
AB  - Here, we describe a new microsporidium Percutemincola moriokae gen. nov., sp.
      nov., which was discovered in the intestinal and hypodermal cells of a wild
      strain of the nematode Oscheius tipulae that inhabits in the soil of Morioka,
      Iwate Prefecture, Japan. The spores of Pe. moriokae had an average size of 1.0 *
      3.8 um and 1.3 * 3.2 um in the intestine and hypodermis, respectively, and
      electron microscopy revealed that they exhibited distinguishing features with
      morphological diversity in the hypodermis. Isolated spores were able to infect a
      reference strain of O. tipulae (CEW1) through horizontal transmission but not the
      nematode Caenorhabditis elegans. Upon infection, the spores were first observed
      in the hypodermis and then in the intestine the following day, suggesting a
      unique infectious route among nematode-infective microsporidia. Molecular
      phylogenetic analysis grouped this new species with the recently identified
      nematode-infective parasites Enteropsectra and Pancytospora forming a
      monophyletic sister clade to Orthosomella in clade IV, which also includes human
      pathogens such as Enterocytozoon and Vittaforma. We believe that this newly
      discovered species and its host could have application as a new model in
      microsporidia-nematode association studies.

PMID- 29661264
TI  - Outbreak of Hepatitis A Virus Infection Among Adult Patients of a Mental Hospital
      - Los Angeles County, 2017.

PMID- 29661265
TI  - Invited commentary in response to: 'Identification of vitamin B12 deficiency in
      vegetarian Indians'.

PMID- 29661266
TI  - Characterization of Polish Steinernema silvaticum isolates (Nematoda:
      Steinernematidae) using morphological and molecular data.
AB  - Four strains of entomopathogenic nematodes were isolated with a live trap method
      in southern Poland. The isolates were identified as Steinernema silvaticum based
      on morphological, morphometric and molecular data. Infective juveniles of Polish
      S. silvaticum isolates differ in body length from S. weiseri (951 vs 740 MUm,
      respectively), and in the hyaline tail portion from S. kraussei (48 vs 38%,
      respectively). First-generation males of S. silvaticum are longer than those of
      S. kraussei, S. weiseri and S. ichnusae (1829 vs 1400, 1180 and 1341 MUm,
      respectively). Males of S. silvaticum and a sister species S. kraussei can be
      distinguished by the distance from the anterior end to the nerve ring (142 vs 105
      MUm), spicule (66 vs 49 MUm) and gubernaculum length (45 vs 33 MUm), and the
      presence of a mucron. The analysis of internal transcribed spacer (ITS), D2-D3
      and cox1 sequences of the tested nematodes revealed differences of 3-5%, 3% and
      12-13%, respectively, from S. kraussei strains. The phylogeny of both nuclear and
      mitochondrial genes indicated close relationships of the Polish S. silvaticum
      isolates with S. kraussei, S. oregonense and S. cholashanense. The reproductive
      isolation of the studied isolates was confirmed by hybridization tests with other
      European feltiae-kraussei group representatives. This study has supplemented the
      original description of S. silvaticum with morphological and morphometric
      characterization of the first-generation males and females. This is also the
      first molecular study of this species based on a multi-gene approach.

PMID- 29661267
TI  - Comparison of Electronic Versus Manual Mass-Casualty Incident Triage.
AB  - : IntroductionMass-casualty incidents (MCIs) easily overwhelm a health care
      facility's human and material resources through the extraordinary influx of
      casualties. Efficient and accurate triage of incoming casualties is a critical
      step in the hospital disaster response.Hypothesis/ProblemTraditionally, triage
      during MCIs has been manually performed using paper cards. This study
      investigated the use of electronic Simple Triage and Rapid Treatment (START)
      triage as compared to the manual method. METHODS: This observational, crossover
      study was performed during a live MCI simulation at an urban, Canadian, Level 1
      trauma center on May 26, 2016. Health care providers (two medical doctors [MDs],
      two paramedics [PMs], and two registered nurses [RNs]) each triaged a total of 30
      simulated patients - 15 by manual (paper-based) and 15 by electronic (computer
      based) START triage. Accuracy of triage categories and time of triage were
      analyzed. Post-simulation, patients and participating health care providers also
      completed a feedback form. RESULTS: There was no difference in accuracy of triage
      between the electronic and manual methods overall, 83% and 80% (P=1.0), between
      providers or between triage categories. On average, triage time using the manual
      method was estimated to be 8.4 seconds faster (P<.001) for PMs; and while small
      differences in triage times were observed for MDs and RNs, they were not
      significant. Data from the participant feedback survey showed that the electronic
      method was preferred by most health care providers. Patients had no preference
      for either method. However, patients perceived the computer-based method as "less
      personal" than the manual triage method, but they also perceived the former as
      "better organized." CONCLUSION: Hospital-based electronic START triage had the
      same accuracy as hospital-based manual START triage, regardless of triage
      provider type or acuity of patient presentations. Time of triage results suggest
      that speed may be related to provider familiarity with a modality rather than the
      modality itself. Finally, according to patient and provider perceptions,
      electronic triage is a feasible modality for hospital triage of mass casualties.
      Further studies are required to assess the performance of electronic hospital
      triage, in the context of a rapid surge of patients, and should consider
      additional efficiencies built in to electronic triage systems. This study
      presents a framework for assessing the accuracy, triage time, and feasibility of
      digital technologies in live simulation training or actual MCIs. BolducC,
      MaghrabyN, FokP, LuongTM, HomierV. Comparison of electronic versus manual mass
      casualty incident triage. Prehosp Disaster Med. 2018;33(3):273-278.

PMID- 29661269
TI  - Dynamic changes in the global transcriptome of bovine germinal vesicle oocytes
      after vitrification followed by in vitro maturation.
AB  - This study was conducted to investigate the effect of vitrification on the
      dynamics of the global transcriptome in bovine germinal vesicle (GV) oocytes and
      their in vitro-derived metaphase II (MII) oocytes. The GV oocytes were vitrified
      using the open-pulled straw method. After warming, GV oocytes and the resulting
      MII-stage oocytes were cultured in vitro for 2h and 24h respectively and were
      then collected. The fresh GV oocytes and their in vitro-derived MII oocytes were
      used as controls. Then, each pool (fresh GV, n=3; vitrified GV, n=4; fresh MII,
      n=1 and MII derived from vitrified GV, n=2) from the different stages was used
      for mRNA transcriptome sequencing. The results showed that the in vitro
      maturation rates of GV oocytes were significantly decreased (32.36% vs 53.14%)
      after vitrification. Bovine GV oocyte vitrification leads to 12 significantly
      upregulated and 19 downregulated genes. After culturing in vitro, the
      vitrification-derived MII oocytes showed 47 significantly upregulated and six
      downregulated genes when compared with those from fresh GV oocytes. Based on
      molecular function-gene ontology terms analysis and the Kyoto encyclopaedia of
      genes (KEGG) pathway database, the differentially expressed genes were associated
      with the pathways of cell differentiation and mitosis, transcription regulation,
      regulation of actin cytoskeleton, apoptosis and so on, which potentially result
      in the lower in vitro development of GV bovine oocytes.

PMID- 29661268
TI  - Degradation or aggregation: the ramifications of post-translational modifications
      on tau.
AB  - Tau protein is encoded in the microtubule-associated protein tau (MAPT) gene and
      contributes to the stability of microtubules in axons. Despite of its basic
      isoelectric point and high solubility, tau is often found in intraneuronal
      filamentous inclusions such as paired helical filaments (PHFs), which are the
      primary constituent of neurofibrillary tangles (NFTs). This pathological feature
      is the nosological entity termed "tauopathies" which notably include Alzheimer's
      disease (AD). A proteinaceous signature of all tauopathies is
      hyperphosphorylation of the accumulated tau, which has been extensively studied
      as a major pharmacological target for AD therapy. However, in addition to
      phosphorylation events, tau undergoes a number of diverse posttranslational
      modifications (PTMs) which appear to be controlled by complex crosstalk. It
      remains to be elucidated which of the PTMs or their combinations have pro
      aggregation or anti-aggregation properties. In this review, we outline the
      consequences of and communications between several key PTMs of tau, such as
      acetylation, phosphorylation, and ubiquitination, focusing on their roles in
      aggregation and degradation. We place emphasis on the structure of tau
      protofilaments from the human AD brain, which may be good targets to modulate
      etiological PTMs which cause tau aggregation. [BMB Reports 2018; 51(6): 265-273].

PMID- 29661270
TI  - Systematic review of the evidence related to mandated nurse staffing ratios in
      acute hospitals.
AB  - Objective The purpose of this systematic review was to evaluate and summarise
      available research on nurse staffing methods and relate these to outcomes under
      three overarching themes of: (1) management of clinical risk, quality and safety;
      (2) development of a new or innovative staffing methodology; and (3) equity of
      nursing workload.Methods The PRISMA method was used. Relevant articles were
      located by searching via the Griffith University Library electronic catalogue,
      including articles on PubMed, Cumulative Index to Nursing and Allied Health
      Literature (CINAHL) and Medline. Only English language publications published
      between 1 January 2010 and 30 April 2016 focusing on methodologies in acute
      hospital in-patient units were included in the present review.Results Two of the
      four staffing methods were found to have evidenced-based articles from empirical
      studies within the parameters set for inclusion. Of the four staffing
      methodologies searched, supply and demand returned 10 studies and staffing ratios
      returned 11.Conclusions There is a need to develop an evidence-based nurse
      sensitive outcomes measure upon which staffing for safety, quality and workplace
      equity, as well as an instrument that reliability and validly projects nurse
      staffing requirements in a variety of clinical settings. Nurse-sensitive
      indicators reflect elements of patient care that are directly affected by nursing
      practice In addition, these measures must take into account patient satisfaction,
      workload and staffing, clinical risks and other measures of the quality and
      safety of care and nurses' work satisfaction. i.What is known about the topic?
      Nurse staffing is a controversial topic that has significant patient safety,
      quality of care, human resources and financial implications. In acute care
      services, nursing accounts for approximately 70% of salaries and wages paid by
      health services budgets, and evidence as to the efficacy and effectiveness of any
      staffing methodology is required because it has workforce and industrial
      relations implications. Although there is significant literature available on the
      topic, there is a paucity of empirical evidence supporting claims of increased
      patient safety in the acute hospital setting, but some evidence exists relating
      to equity of workload for nurses.What does this paper add? This paper provides a
      contemporary qualitative analysis of empirical evidence using PRISMA methodology
      to conduct a systematic review of the available literature. It demonstrates a
      significant research gap to support claims of increased patient safety in the
      acute hospital setting. The paper calls for greatly improved datasets upon which
      research can be undertaken to determine any associations between mandated patient
      to nurse ratios and other staffing methodologies and patient safety and quality
      of care.What are the implications for practitioners? There is insufficient
      contemporary research to support staffing methodologies for appropriate staffing,
      balanced workloads and quality, safe care. Such research would include the
      establishment of nurse-sensitive patient outcomes measures, and more robust
      datasets are needed for empirical analysis to produce such evidence.

PMID- 29661271
TI  - Antimicrobial peptide expression in a wild tobacco plant reveals the limits of
      host-microbe-manipulations in the field.
AB  - Plant-microbe associations are thought to be beneficial for plant growth and
      resistance against biotic or abiotic stresses, but for natural ecosystems, the
      ecological analysis of microbiome function remains in its infancy. We used
      transformed wild tobacco plants (Nicotiana attenuata) which constitutively
      express an antimicrobial peptide (Mc-AMP1) of the common ice plant, to establish
      an ecological tool for plant-microbe studies in the field. Transgenic plants
      showed in planta activity against plant-beneficial bacteria and were phenotyped
      within the plants' natural habitat regarding growth, fitness and the resistance
      against herbivores. Multiple field experiments, conducted over 3 years, indicated
      no differences compared to isogenic controls. Pyrosequencing analysis of the root
      associated microbial communities showed no major alterations but marginal effects
      at the genus level. Experimental infiltrations revealed a high heterogeneity in
      peptide tolerance among native isolates and suggests that the diversity of
      natural microbial communities can be a major obstacle for microbiome
      manipulations in nature.

PMID- 29661272
TI  - Hexameric and pentameric complexes of the ExbBD energizer in the Ton system.
AB  - Gram-negative bacteria import essential nutrients such as iron and vitamin B12
      through outer membrane receptors. This process utilizes proton motive force
      harvested by the Ton system made up of three inner membrane proteins, ExbB, ExbD
      and TonB. ExbB and ExbD form the proton channel that energizes uptake through
      TonB. Recently, crystal structures suggest that the ExbB pentamer is the
      scaffold. Here, we present structures of hexameric complexes of ExbB and ExbD
      revealed by X-ray crystallography and single particle cryo-EM. Image analysis
      shows that hexameric and pentameric complexes coexist, with the proportion of
      hexamer increasing with pH. Channel current measurement and 2D crystallography
      support the existence and transition of the two oligomeric states in membranes.
      The hexameric complex consists of six ExbB subunits and three ExbD transmembrane
      helices enclosed within the central channel. We propose models for
      activation/inactivation associated with hexamer and pentamer formation and
      utilization of proton motive force.

PMID- 29661274
TI  - Granular cell tumor experience at a comprehensive cancer center.
AB  - BACKGROUND: Granular cell tumors (GCTs) are rare lesions occurring almost
      anywhere in the body. Multiple case reports have been published. However, there
      are very few large-scale studies regarding GCT. The aim of this study was to
      define characteristics, treatment patterns and outcomes of patients with GCT.
      METHODS: An institutional review board-approved retrospective chart review was
      performed. Descriptive statistics, chi-square analyses, and Kaplan-Meier survival
      estimates were produced. RESULTS: Fifty patients were treated for GCT at our
      institution between 1992 and 2015. The median age was 47 y; 62% of patients were
      female and 64% were whites. Median tumor size was 0.8 cm. Four percent of
      patients had malignant tumors, 10.0% had atypical tumors, and 86.0% had benign
      tumors. The most frequent location of tumors was the gastrointestinal tract (n =
      30; 60%), followed by skin/subcutaneous tissues (n = 19; 38%), then respiratory
      tract (n = 1; 2%). Most patients underwent surgical excision or endoscopic
      removal of their tumors without prior biopsy. Three patients (6%) had multifocal
      tumors; they were more likely to experience recurrence than patients with
      unifocal tumors (33.3% versus 10.6%, respectively; P = 0.05). Six patients
      (12.0%) experienced recurrence, with a median time to recurrence of 13.5 mo.
      Overall cancer-specific 5-y survival was 98.0%. Overall recurrence-free 5-y
      survival was 86.4%. Patients with atypical tumors had a lower recurrence-free 5-y
      survival rate than those with benign tumors (75.0% versus 89.7%, respectively; P
      = 0.04). CONCLUSIONS: Patients with GCT fair well, particularly when tumors are
      benign. Patients with multifocal tumors are more likely to experience recurrence
      and should be closely monitored.

PMID- 29661275
TI  - Preinjury statin use and thromboembolic events in trauma: a 10-year retrospective
      evaluation.
AB  - BACKGROUND: Traumatic injury is well known to increase the risk of venous
      thromboembolic events (VTEs), occurring in up to 58% of trauma patients. Statin
      medications have significant anti-inflammatory properties and have been shown to
      reduce the risk of VTE. We hypothesized that trauma patients who received statin
      medication before injury would have a lower incidence of VTE after injury.
      METHODS: A 10-y retrospective review identified all patients admitted to our
      trauma service with an injury severity score >9 and an intensive care unit stay
      of >3 d. This population was categorized as either "statin recipient" (SR) or
      "statin naive," with subsequent categorical division by occurrence of VTE. Our
      primary outcome measure was the occurrence of documented VTE in both statin naive
      and SR subjects. RESULTS: A total of 2519 trauma patients were included with 97
      (3.8%) developing VTE. Pretrauma statin use in males remained as an independent
      predictor of VTE (odds ratio = 2.25, 95% confidence interval = 1.25-4.04, P <
      0.01). The median time to VTE onset was 3 d longer in SRs (10.0 d; confidence
      interval = 7.3-12.7, P < 0.05). CONCLUSIONS: Pretrauma statin use does not appear
      to have a protective benefit of VTE prevention in trauma patients, as we have
      shown pretrauma SR male trauma patients to have a twofold increased incidence of
      VTE. However, when considering the 3 d longer median time to VTE onset found in
      SRs, we consider the protective benefit of statin use reported in the current
      literature as likely attributable to this observed delayed onset.

PMID- 29661273
TI  - IRS-1 acts as an endocytic regulator of IGF-I receptor to facilitate sustained
      IGF signaling.
AB  - Insulin-like growth factor-I receptor (IGF-IR) preferentially regulates the long
      term IGF activities including growth and metabolism. Kinetics of ligand-dependent
      IGF-IR endocytosis determines how IGF induces such downstream signaling outputs.
      Here, we find that the insulin receptor substrate (IRS)-1 modulates how long
      ligand-activated IGF-IR remains at the cell surface before undergoing endocytosis
      in mammalian cells. IRS-1 interacts with the clathrin adaptor complex AP2. IRS-1,
      but not an AP2-binding-deficient mutant, delays AP2-mediated IGF-IR endocytosis
      after the ligand stimulation. Mechanistically, IRS-1 inhibits the recruitment of
      IGF-IR into clathrin-coated structures; for this reason, IGF-IR avoids rapid
      endocytosis and prolongs its activity on the cell surface. Accelerating IGF-IR
      endocytosis via IRS-1 depletion induces the shift from sustained to transient Akt
      activation and augments FoxO-mediated transcription. Our study establishes a new
      role for IRS-1 as an endocytic regulator of IGF-IR that ensures sustained IGF
      bioactivity, independent of its classic role as an adaptor in IGF-IR signaling.

PMID- 29661276
TI  - Postoperative morbidity and mortality for malignant colon obstruction: the
      American College of Surgeon calculator reliability.
AB  - BACKGROUND: The American College of surgical risk calculator (SRC) score has
      never been validated specifically for surgery in emergency. The objective was to
      evaluate the reliability of this calculator in patients with malignant colon
      obstruction. MATERIALS AND METHODS: We retrospectively have analyzed the
      morbidity and mortality observed in operated patients. Risk factors for
      postoperative morbidity and mortality were analyzed by logistic regression model.
      We have compared the morbidity and mortality estimated by the SRC score with that
      observed using the Brier Score (BS). A BS of 0 indicated perfect prediction,
      whereas a BS of 1 indicated the poorest prediction. RESULTS: Sixty-nine patients
      aged 75 y (41-93) have been operated on emergency from November 2001 to August
      2015. The tumor was localized in the sigmoid in 33 cases (48%), in the splenic
      flexure in nine cases (13%), and in the right colon in 17 cases (25%). The
      surgical procedures were as follows: right colectomy with anastomosis (29%),
      diverting proximal iliac colostomy (23%), and subtotal colectomy with anastomosis
      (19%). The SRC score indicated a good predictivity for mortality (9.8% predicted
      versus 8.7% observed, BS = 0.058), for morbidity (33.4% versus 40.6%, BS =
      0.209), and for serious morbidity (25.5% versus 17.4%, BS = 0.131). In
      multivariate analysis, SRC was an independent risk factor for mortality (P =
      0.030 odds ratio [OR] = 1.07 [1.01-1.15]) and morbidity (P = 0.001 OR = 1.16
      [1.08-1.27]). CONCLUSIONS: SRC score is a reliable tool for assessing the
      morbidity and mortality of obstructive colon cancer and could help with adapting
      the surgical gesture to the risks predicted.

PMID- 29661277
TI  - RT-PCR of peritoneal washings predicts peritoneal pancreatic cancer recurrence.
AB  - BACKGROUND: Peritoneal recurrence of pancreatic cancer is a frequent and lethal
      outcome after R0 resection. A method to predict peritoneal recurrence could be
      helpful in its prevention. MATERIALS AND METHODS: Peritoneal washings were
      prospectively obtained from 29 patients in whom R0 resection was performed.
      Cytological examination (CY) and real-time reverse transcription polymerase chain
      reaction (RT-PCR) of the peritoneal washing for the detection of cancer-related
      genes, CEACAM5, KRT7, KRAS, and MUC1, were performed. Clinicopathological
      characteristics and real-time RT-PCR results of the peritoneal washing were
      compared between patients whose pancreatic cancer recurred peritoneally (n = 7)
      and those patients who it did not recur (n = 22). RESULTS: Only one CY-positive
      (CY+) case was detected, and that patient recurred. MUC1 mRNA expression was
      significantly higher in the recurrence group (P = 0.015). Cumulative incidence
      function analysis demonstrated that peritoneal recurrence rate was significantly
      higher in MUC1-positive (MUC1+) patients (P = 0.044). MUC1+ patients had
      significantly decreased disease-free survival (P = 0.009) and disease-specific
      survival (P = 0.031). MUC1 protein was detected in the primary tumor in 18 of 29
      patients. However, no significant difference was observed in the expression of
      MUC1 protein in peritoneal washings from the primary tumor (P = 0.579).
      CONCLUSIONS: High expression of MUC1 mRNA in peritoneal washings is a significant
      risk factor for peritoneal recurrence of pancreatic cancer after R0 resection
      along with poor disease-specific survival. RT-PCR of MUC1 mRNA in peritoneal
      washing may be useful for individualization of adjuvant chemotherapy.

PMID- 29661278
TI  - Comparing survival outcomes of gross total resection and subtotal resection with
      radiotherapy for craniopharyngioma: a meta-analysis.
AB  - BACKGROUND: Recent studies suggest that subtotal resection (STR) followed by
      radiation therapy (RT) is an appealing alternative to gross total resection (GTR)
      for craniopharyngioma, but it remains controversial. We conducted a meta-analysis
      to determine whether GTR is superior to STR with RT for craniopharyngioma.
      MATERIALS AND METHODS: A systematic search was performed for articles published
      until October 2017 in the PubMed, Embase, and Cochrane Central databases. The
      endpoints of interest are overall survival and progression-free survival. Pooled
      hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were
      calculated using a fixed or random-effects model. The data were analyzed using
      Review Manager 5.3 software. RESULTS: A total of 744 patients (seven cohort
      studies) were enrolled for analyses. There were no significant differences
      between the GTR and STR with RT groups when the authors compared the pooled HRs
      at the end of the follow-up period. Overall survival (pooled HR = 0.76, 95% CI:
      0.46-1.25, P = 0.28) and progression-free survival (pooled HR = 1.52, 95% CI:
      0.42-5.44, P = 0.52) were similar between the two groups. CONCLUSIONS: The
      current meta-analysis suggests that GTR and STR with RT have the similar survival
      outcomes for craniopharyngioma.

PMID- 29661279
TI  - Sources of distress among patients undergoing surgery for colorectal cancer: a
      qualitative study.
AB  - BACKGROUND: Distress is common among cancer and surgical patients and can lead to
      worse outcomes if untreated. The objective of this study was to explore sources
      of distress among colorectal cancer patients undergoing surgery. MATERIALS AND
      METHODS: This was a qualitative study using in-depth, semistructured, one-on-one
      interviews in an academic setting. Patients were recruited if they had a
      pathologically confirmed diagnosis of colon or rectal cancer. Purposive sampling
      was used to recruit patients who were about to undergo (preoperative), or had
      recently undergone (postoperative), curative resection for colorectal cancer.
      RESULTS: All participants (n = 24) reported experiencing distress during
      treatment. Participants identified sources of distress preoperatively (negative
      emotional reaction to diagnosis, distress from preconception of cancer diagnosis,
      and distress interacting with healthcare system). Sources of distress during in
      hospital recovery included negative emotional reaction to having a surgery and
      negative emotions experienced in the hospital. Postoperative sources of distress
      included mismatch of expectations and experience of recovery, dealing with
      distressing physical symptoms and complications after surgery, and distress
      worrying about recurrence. Participants identified other sources of distress that
      were not time-specific (distress related to social support network, from
      disruption of life, and worrying about death). CONCLUSIONS: Our results highlight
      a potential role for a comprehensive screening program to identify which patients
      require assistance with addressing sources of distress during the surgical
      experience. Understanding how sources of distress may vary by time will help us
      tailor interventions at different time points of the surgical experience.

PMID- 29661280
TI  - Prognostic value of neoadjuvant treatment response in locally advanced rectal
      cancer.
AB  - BACKGROUND: For locally advanced rectal cancer, response to neoadjuvant radiation
      has been associated with improved outcomes but has not been well characterized in
      general practice. The goals of this study were to describe disease response rates
      after neoadjuvant treatment and to evaluate the association between disease
      response and survival. MATERIALS AND METHODS: Retrospective cohort study of
      patients aged 18-80 y with clinical stage II and III rectal adenocarcinoma in the
      National Cancer Database (2006-2012). All patients underwent radical resection
      after neoadjuvant treatment. Treatment responses were defined as follows: no
      tumor response; intermediate-T and/or N downstaging with residual disease; and
      complete-ypT0N0. Multivariable, multinomial regression was used to evaluate the
      association between neoadjuvant radiation use and disease response. Multivariable
      Cox regression was used to evaluate the association between disease response and
      overall risk of death. RESULTS: Among 12,024 patients, 12% had a complete and 30%
      an intermediate response. Neoadjuvant chemotherapy alone was less likely to
      achieve an intermediate (relative risk ratio: 0.70 [0.56-0.88]) or a complete
      response (relative risk ratio: 0.59 [0.41-0.84]) relative to neoadjuvant
      radiation. Tumor response was associated with improved 5-y overall survival
      (complete = 90.2%, intermediate = 82.0%, no response = 70.5%; log-rank, P <
      0.001). Complete and intermediate pathologic responses were associated with
      decreases in risk of death (hazard ratio: 0.40 [0.34-0.48] and 0.63 [0.57-0.69],
      respectively) compared to no response. Primary tumor and nodal response were
      independently associated with decreased risk of death. CONCLUSIONS: Neoadjuvant
      radiation is associated with treatment response, and pathologic response is
      associated with improved survival. Pathologic response may be an early benchmark
      for the oncologic effectiveness of neoadjuvant treatment.

PMID- 29661281
TI  - Acute high-altitude exposure shortens survival after uncontrolled hemorrhagic
      shock in rats.
AB  - BACKGROUND: Uncontrolled hemorrhage (UH) remains the most common cause of death
      on the battlefield. This study examined the pathophysiological characteristics of
      UH in rats acutely exposed to high altitude. MATERIAL AND METHODS: Rats raised at
      sea level were randomly divided into two groups. Rats in the high-altitude group
      were exposed to hypobaric hypoxia in a hypobaric chamber (simulating 4000 m above
      sea level) for 2 d and then were performed a hemorrhagic shock protocol in the
      hypobaric chamber. Rats that underwent the same hemorrhage procedure at sea level
      were used as control. Anesthetized rats were bled to maintain their mean arterial
      pressure at 45 mmHg for 1 h. The distal quarter of the tail was amputated to
      allow free blood loss. After 1 h, the tail cut was ligated to induce hemostasis.
      mean arterial pressure, acid-base balance, blood loss, and survival were
      recorded. Rats were killed, and tissues were obtained for histological analysis.
      RESULTS: Rats in the high-altitude group suffered less uncontrolled blood loss,
      more severe acidosis (lower pH and base excess), and inferior tissue oxygen
      supply (lower oxygen saturation and higher arterial lactate concentration) during
      the hemorrhage periods compared with the control group. Survival rates were
      significantly lower in the high-altitude group than those in the control group (P
      < 0.05), which was consistent with the results of pathological tissue injury.
      CONCLUSIONS: In this rat model of hemorrhagic shock, acute high-altitude exposure
      resulted in decreased UH but more serious hemorrhagic shock injuries than that at
      sea level.

PMID- 29661282
TI  - Impact of fresh frozen plasma transfusion on postoperative inflammation and
      prognosis of colorectal liver metastases.
AB  - BACKGROUND: Blood transfusion has been reported to be associated with
      immunomodulation and poor oncologic outcomes in several malignancies. The aim of
      the study is to investigate the influence of the use of fresh frozen plasma (FFP)
      on long-term outcomes in patients with colorectal liver metastases (CRLM) after
      hepatic resection. MATERIALS AND METHODS: The study comprised 127 patients who
      had undergone first hepatic resection for CRLM between April 2000 and December
      2013. We retrospectively investigated the influence of the use of FFP on disease
      free survival as well as overall survival and assessed the impact of such a
      practice on postoperative inflammation markers. RESULTS: In multivariate
      analysis, more than four lymph node metastases of the primary cancer (P = 0.001),
      bilobar distribution (P = 0.002), and perioperative FFP transfusion (P = 0.005)
      were independent risk factors for cancer recurrence, while more than four lymph
      node metastases of the primary cancer (P < 0.001), presence of neoadjuvant
      chemotherapy (P = 0.002), and perioperative FFP transfusion (P = 0.004) were
      independent risk factors for poor overall survival. In patients who underwent FFP
      transfusion, tumor size (P = 0.004), anatomic resection (P < 0.001), duration of
      operation (P = 0.039), and intraoperative blood loss (P < 0.001) were
      significantly greater. Moreover, FFP transfusion was associated with a higher
      white blood cell level on postoperative day 3 (P < 0.001) and day 5 (P = 0.010)
      and lower serum C-reactive protein level on postoperative day 1 (P < 0.001) and
      day 3 (P = 0.017). CONCLUSIONS: Perioperative FFP transfusion is independently
      associated with poor long-term outcomes in patients with CRLM after hepatic
      resection. FFP may have an influence on postoperative inflammation because of its
      immunosuppressive effects.

PMID- 29661283
TI  - 2-Octylcyanoacrylate for the prevention of anastomotic leak.
AB  - BACKGROUND: Anastomotic leak after colorectal surgery is a significant cause of
      morbidity and mortality. The aim of this study was to evaluate the impact of a
      reinforced colo-colonic anastomosis with tissue adhesive, 2-octylcyanoacrylate (2
      OCA), on the integrity of anastomotic healing as measured by anastomotic bursting
      pressure. METHODS: Sixty-eight female Sprague-Dawley rats underwent a
      rectosigmoid colon transection and a sutured end-to-end anastomosis followed by
      randomization to receive no further intervention or reinforcement with the tissue
      adhesive, 2-OCA. After seven postoperative days, a macroscopic assessment of the
      anastomosis, mechanical assessment to determine anastomotic bursting pressure,
      and a detailed semi-quantitative histopathologic healing assessment were
      performed. RESULTS: Thirty-four animals were randomized to each group. Study
      characteristics did not differ between the groups. There was also no difference
      in the degree of adhesions present postoperatively. Although there was no
      difference between the net proximal and distal luminal areas in the two groups
      (0.37 cm2versus 0.55 cm2, P = 0.26), the 2-OCA group exhibited evidence of
      stricture in 15% of anastomoses as compared with 3% in the suture-only group (P <
      0.0001). Histologically, the presence of only fibroblasts density was
      statistically more evident in the 2-OCA group compared with the sutured-only
      anastomosis (P = 0.0183). There was not a significant increase in mechanical
      strength in the 2-OCA group (238.9 mm Hg) versus in the suture-only group (231.8
      mm Hg). There was no difference in the rate of anastomotic leak in the 2-OCA as
      compared with the suture-only group (9.1 versus 8.8%). CONCLUSIONS: Application
      of 2-OCA to reinforce a colo-colonic anastomosis clinically provides no benefit
      to its mechanical strength and detrimentally increases the rate of obstruction
      and/or stricture in this in vivo model.

PMID- 29661284
TI  - Pyruvate in reduced osmolarity oral rehydration salt corrected lactic acidosis in
      sever scald rats.
AB  - BACKGROUND: A novel pyruvate-based oral rehydration salt (Pyr-ORS) was
      demonstrated of superiority over bicarbonate- or citrate-based one to preserve
      organ function and correct lactic acidosis in rehydration of lethal shock in
      animals. This study further compared these effects between low-osmolar Pyr-ORS
      and equimolar citrate-based counterpart. METHODS: Eighty rats, using a fatal burn
      shock model, were randomized into four groups (two subgroups per group: n = 10):
      the sham group (group SR), Pyr-ORS group (group PR), WHO-ORS III group (group
      CR), and no rehydration group. ORS was delivered by manual gavage during 24 h
      following burns. Oral administration consisted of half of counted volume in the
      initial 8 h plus the rest in the later 16 h. Systemic hemodynamics, visceral
      organ surface blood flow, organ function, and metabolic acidosis were determined
      at 8 h and 24 h after burn. Another set of rats with identical surgical
      procedures without tests was observed for survival. RESULTS: Survival was
      markedly improved in the groups PR and CR; the former showed a higher survival
      rate than the latter at 24 h (40% versus 20%, P < 0.05). Systemic hemodynamics,
      visceral blood flow, and function of heart, liver, and kidney were greatly
      restored in group PR, compared with group CR (all P < 0.05). Hypoxic lactic
      acidosis was efficiently reversed in group PR, instead of group CR, (pH 7.36
      versus 7.11, base excess 2.1 versus -9.1 mmol/L, lactate 4.28 versus 8.18 mmol/L;
      all P < 0.05) at 24 h after injury. CONCLUSIONS: Pyruvate was advantageous over
      citrate in low-osmolar ORS for protection of organs and survival; pyruvate, but
      not citrate, in the ORS corrected hypoxic lactic acidosis in rats subjected to
      lethal burn shock in 24 h.

PMID- 29661285
TI  - Extending surgeon response times in tier 2 traumas does not adversely affect
      patient outcomes.
AB  - BACKGROUND: The presence of a trauma surgeon during patient resuscitations is
      required at most American College of Surgeons-verified trauma centers despite
      little evidence showing improved patient outcomes in the less-than-critically
      injured (Tier 2) trauma patients. This study was designed to identify the impact
      of extending required surgeon response times on outcomes in tier 2 trauma
      patients. METHODS: An American College of Surgeons-verified level 2 trauma center
      extended the maximum allowed surgeon response time for tier 2 activations from 60
      min to 120 min on November 1, 2011. Surgeon response time and patient outcomes of
      the retrospective control group (January 1, 2008-October 31, 2011) were then
      compared with the prospective test group (November 1, 2011-December 31, 2014).
      Primary outcomes included mortality and hospital length of stay (HLOS). Secondary
      outcomes were emergency department length of stay, and time from ED arrival to CT
      scan. A subset analysis of all patients evaluated by a surgeon within 60 min of
      arrival versus those evaluated by a surgeon after 60 min was also performed.
      RESULTS: The control and test groups were composed of 757 and 792 patients, and
      their mean injury severity score was 9.0 and 6.0, respectively. Emergency
      department length of stay showed a statistically significant increase of 12 min,
      whereas HLOS was unchanged throughout the study. Mortality was not significantly
      different between the groups. Subset analysis revealed a median surgeon arrival
      time of 15 min in the <60-min group and 85 min in the >60-min group, whereas the
      injury severity score, HLOS, and mortality were not significantly different
      between these subsets. No correlation existed between these outcomes and surgeon
      arrival time. CONCLUSIONS: Doubling required surgeon response time in tier 2
      trauma patients does not produce negative outcomes in this patient group.
      Mandatory surgeon response times in similar patient groups can be re-evaluated to
      allow for greater flexibility of a limited surgeon workforce while still
      providing safe care.

PMID- 29661286
TI  - Comparison of zone 3 Resuscitative Endovascular Balloon Occlusion of the Aorta
      and the Abdominal Aortic and Junctional Tourniquet in a model of junctional
      hemorrhage in swine.
AB  - BACKGROUND: Traumatic injuries to the pelvis and high junctional injuries are
      difficult to treat in the field; however, Resuscitative Endovascular Balloon
      Occlusion of the Aorta (REBOA) and the Abdominal Aortic and Junctional Tourniquet
      (AAJT) constitute two promising treatment modalities. The aim of this study is to
      use a large animal model of pelvic hemorrhage to compare the survival,
      hemostatic, hemodynamic, and metabolic profile of both techniques. METHODS:
      Yorkshire swine (n = 10, 70-90 kg) underwent general anesthesia, instrumentation,
      and surgical isolation of the femoral artery. Uncontrolled hemorrhage was
      initiated by an arteriotomy. Animals were randomly allocated to either REBOA or
      AAJT. Following completion of device application, both groups received a 500 mL
      Hextend bolus. After 1 hour, the injured femoral artery was ligated to simulate
      definitive hemostasis followed by a second Hextend bolus and device removal.
      Animals were observed for two more hours. Physiological data were collected
      throughout the experiments and compared between groups. RESULTS: Both techniques
      achieved 100% hemostasis, and all animals survived the entire experiment except
      one in the REBOA group. During the hour treatment phase, the AAJT group had a
      higher mean arterial pressure than the REBOA group (59.9 +/- 16.1 versus 44.6 +/-
      9.8 mm Hg, respectively; P < 0.05). The AAJT-treated group had higher lactate
      levels than the REBOA-treated group (4.5 +/- 2.0 versus 3.2 +/- 1.3 mg/dL,
      respectively; P < 0.05). CONCLUSIONS: Despite their mechanistic differences, both
      techniques achieved a similar hemostatic, hemodynamic, and metabolic profile.
      Some differences do exist including lactate levels and blood pressure.

PMID- 29661287
TI  - Prognostic significance of nuclear factor of activated T-cells 5 expression in
      non-small cell lung cancer patients who underwent surgical resection.
AB  - BACKGROUND: Nuclear factor of activated T-cells 5 (NFAT5) is known to be
      correlated with migration or invasion of tumor cells based on previous in vitro
      studies. The aim of this study was to analyze the relationship between NFAT5
      expression and clinical prognosis in non-small cell lung cancer (NSCLC) patients
      who underwent surgical resection. MATERIALS AND METHODS: A total of 92 NSCLC
      patients who underwent surgical resection were enrolled. The tissue microarray
      core was obtained from surgically resected tumor specimens. NFAT5 expression was
      evaluated by immunohistochemistry. Relationships of NFAT5 expression with disease
      recurrence, overall survival, and disease-free survival (DFS) were analyzed.
      RESULTS: The mean age of 92 patients was 63.7 y. The median follow-up duration
      was 63.3 mo. Fifty-one (55%) patients exhibited positive expression of NFAT5.
      Disease recurrence in the NFAT5-positive group was significantly (P = 0.022)
      higher than that in the NFAT5-negative group. NFAT5-positive expression (odds
      ratio: 2.632, 95% confidence interval: 1.071-6.465, P = 0.035) and pathologic N
      stage (N1-2 versus N0; odds ratio: 3.174, 95% confidence interval: 1.241-8.123, P
      = 0.016) were independent and significant risk factors for disease recurrence.
      DFS of the NFAT5-positive group was significantly worse than that of the NFAT5
      negative group (89.7 versus 48.7 mo, P = 0.011). A multivariate analysis
      identified NFAT5 expression (P < 0.029) as a significant independent risk factor
      for DFS of patients with postoperative pathologic T and N stages (P < 0.001 and P
      = 0.017, respectively). CONCLUSIONS: NFAT5 expression is a useful prognostic
      biomarker for NSCLC patients who underwent surgical resection.

PMID- 29661288
TI  - Hepatocyte transplantation: past efforts, current technology, and future
      expansion of therapeutic potential.
AB  - Hepatic cell transplantation (HCT) continues to garner interest as an alternative
      to orthotopic liver transplantation and the attendant donor shortage. When
      compared with solid organ transplantation, advantages of cell transplantation
      include the potential to treat more patients with a considerably less invasive
      procedure, the ability to utilize organs otherwise unsuitable for transplant, and
      leaving the native organ in situ with the potential for regeneration. While
      studies date back to the early 1960s, advancement of clinical application has
      been slow due in part to limitations of suitable tissue supplies and reproducible
      robust techniques. Compared with orthotopic liver transplantation, there are
      fewer absolute contraindications for donor selection. And, current techniques
      used to harvest, isolate, store, and even transfuse cells vary little between
      institutions. Significant variation is seen due to a lack of consensus with
      maintenance therapy. Although the ideal recipient has not been clearly
      identified, the most significant results have been demonstrated with correction
      of congenital metabolic liver disorders, with a few trials examining its utility
      in cirrhotics and more recently acute liver failure. The most exciting new topic
      of discussion examines techniques to improve engraftment, with many such as
      ischemic preconditioning and nonselective partial embolization (microbead
      therapy), while not yet used in HCT study, showing promise in solid organ
      research. Advancements in HCT, although slow in progress, have great potential in
      the ability to alleviate the burden faced in solid organ transplantation and
      possibly become a long-term viable option, beyond that of a bridge or salvage
      therapy.

PMID- 29661289
TI  - A nomogram to predict lymph node metastasis before resection in intrahepatic
      cholangiocarcinoma.
AB  - BACKGROUND: In this study, we developed and validated a nomogram to predict lymph
      node metastasis before surgery in patients with intrahepatic cholangiocarcinoma
      (ICC). METHODS: Using the data from January 2006 to January 2015, we enrolled a
      total of 218 eligible patients with clinicopathologically confirmed ICC as a
      primary cohort to develop the nomogram. After various variables before surgery
      were analyzed by multivariable logistic regression, we combined the preoperative
      carbohydrate antigen 19-9, primary site of tumor, lymphonodus size on computed
      tomography imaging, tumor growth pattern, and (if applicable) histologic grade to
      make two different predictive nomograms. Then, the results were validated in 62
      consecutive ICC patients from February 2015 to December 2016. We also compared
      the performance of the different nomograms via calibration, discrimination, and
      clinical use. RESULTS: The nomogram displayed fine discrimination (the
      concordance index, 0.761) and fine calibration in the primary cohort. When
      applied to the validation cohort, the nomogram also showed fine discrimination
      (concordance index, 0.794) and fine calibration. After adding the histologic
      grade to the nomogram, the integrated discrimination for predictive performance
      improved significantly. Finally, the clinical usefulness of predictive nomogram
      was proven via the decision curve analysis. CONCLUSIONS: The proposed nomograms
      can be selectively used to achieve more accurate lymph node metastasis
      predictions before surgery in patients with ICC, and this information can help
      with clinical management.

PMID- 29661290
TI  - Factors affecting the caloric and protein intake over time in critically ill
      trauma patients.
AB  - BACKGROUND: Major trauma leads to increased nutritional requirements. However,
      little is known about the actual amount of calories and protein administered and
      the factors affecting the intake over time in critically ill trauma patients.
      METHODS: Prospective study including 100 trauma patients admitted to the Los
      Angeles County + University of Southern California Medical Center intensive care
      unit between March 2014 and October 2014. Inclusion criteria were age > 16 y,
      surgery at admission, and no oral nutrition. The caloric and protein intake was
      recorded, and requirements were calculated daily for 28 d. The nutritional intake
      and the impact of clinical factors on the intake over time were assessed using
      mixed model analysis. RESULTS: The caloric and protein intake significantly
      increased over time, but the median intake did not meet the median calculated
      requirements at any time. Multivariable analysis revealed a smaller increase of
      the nutritional intake over time in patients with an injury severity score > 45,
      whereas penetrating injury and laparotomy were associated with a higher increase
      of the intake. Body mass index scores >= 30 kg/m2, traumatic brain injury, and
      gastrointestinal tract injuries were associated with a smaller increase of the
      caloric intake over time. CONCLUSIONS: The median nutritional intake did not meet
      the median calculated requirements over time. A smaller increase of the
      nutritional intake over time was found in patients with a higher injury burden,
      whereas penetrating injury and laparotomy were associated with a higher increase
      of the intake. Higher body mass index scores, traumatic brain injury, and
      gastrointestinal tract injuries were associated with a smaller increase of the
      caloric intake over time. These clinical factors can help to adjust the
      nutritional support in critically ill trauma patients.

PMID- 29661291
TI  - Hemodialysis patients have worse outcomes after infrageniculate revascularization
      procedures.
AB  - BACKGROUND: Hemodialysis (HD) has been shown to be an independent predictor of
      poor outcomes after femoropopliteal revascularization procedures in patients with
      chronic limb-threatening ischemia. However, HD patients tend to have isolated
      infrageniculate disease, an anatomic risk factor for inferior patency. We aimed
      to compare outcomes for HD versus non-HD patients after infrageniculate open
      lower extremity bypass (LEB) and endovascular peripheral vascular interventions
      (PVIs). METHODS: Data from the Society for Vascular Surgery Vascular Quality
      Initiative database (2008-2014) were analyzed. All patients undergoing
      infrageniculate LEB or PVI for rest pain or tissue loss were included. One-year
      primary patency (PP), secondary patency (SP), and major amputation outcomes were
      analyzed for HD versus non-HD patients stratified by treatment approach using
      both univariable and multivariable analyses. RESULTS: A total of 1688 patients
      were included, including 348 patients undergoing LEB (HD = 44 versus non-HD =
      304) and 1340 patients undergoing PVI (HD = 223 versus non-HD = 1117). Patients
      on HD more frequently underwent revascularization for tissue loss (89% versus
      77%, P < 0.001) and had >=2 comorbidities (91% versus 76%, P < 0.001). Among
      patients undergoing LEB, 1-y PP (66% versus 69%) and SP (71% versus 78%) were
      similar for HD versus non-HD (P >= 0.25) groups, but major amputations occurred
      more frequently in the HD group (27% versus 14%; P = 0.03). Among patients
      undergoing PVI, 1-y PP (70% versus 78%) and SP (82% versus 90%) were lower and
      the frequency of major amputations was higher (27% versus 10%) for HD patients
      (all, P <= 0.02). After correcting for baseline differences between the groups,
      outcomes were similar for HD versus non-HD patients undergoing LEB (P >= 0.21)
      but persistently worse for HD patients undergoing PVI (all, P <= 0.006).
      CONCLUSIONS: HD is an independent predictor of poor patency and higher risk of
      major amputation after infrageniculate endovascular revascularization procedures
      for the treatment of chronic limb-threatening ischemia. The use of endovascular
      interventions in these higher risk patients is not associated with improved limb
      salvage outcomes and may be an inappropriate use of healthcare resources.

PMID- 29661292
TI  - Etanercept restores vasocontractile sensitivity affected by mesenteric ischemia
      reperfusion.
AB  - BACKGROUND: The aim of the study is to evaluate in vivo and in vitro effects of
      etanercept, a soluble tumor necrosis factor receptor, on the contractile
      responses of superior mesenteric artery in an experimental mesenteric ischemia
      and reperfusion model. MATERIAL AND METHODS: After obtaining animal ethics
      committee approval, 24 Sprague-Dawley rats were allocated to three groups.
      Control group (Gr C, n = 6) underwent a sham operation, whereas
      ischemia/reperfusion and treatment groups underwent 90 min ischemia and 24-h
      reperfusion (Gr I/R, n = 12; Gr I/R+E, n = 6). The treatment group received 5
      mg/kg etanercept intravenously at the beginning of reperfusion. At the end of
      reperfusion, all animals were sacrificed, and third branch of superior mesenteric
      artery was dissected for evaluation of contractile responses. In vitro effects of
      etanercept on vasocontractile responses were also evaluated. The excised ileums
      were analyzed under light microscope. Two-way analysis of variance following
      Bonferroni post hoc test was used for evaluation of contractile responses.
      RESULTS: Endothelin-1 and phenylephrine-mediated vasocontractile sensitivity were
      found increased in Gr I/R when compared with Gr C. Both intravenous
      administration and organ bath incubation of etanercept decreased the sensitivity
      of contractile agents for Gr I/R. Mucosal injury, lamina propria disintegration,
      and denuded villous tips were observed in Gr I/R, whereas the epithelial injury
      and the subepithelial edema were found to be milder in Gr I/R+E. CONCLUSIONS:
      Etanercept can be a promising agent in mesenteric ischemic reperfusion injury as
      it does not only inhibit inflammation by blocking tumor necrosis factor-alpha in
      circulation but also restores vascular contractility during reflow. These
      findings support an unexplained recuperative effect of drug beyond its anti
      inflammatory effects.

PMID- 29661293
TI  - Stent graft placement versus angioplasty for hemodialysis access failure: a meta
      analysis.
AB  - BACKGROUND: Hemodialysis is a common treatment for end-stage renal disease, and
      maintenance of access patency remains a key issue. Angioplasty is recommended as
      the first choice for access stenosis, but it poses a risk of a high rate of
      restenosis. Stent graft placement can generate a high patency rate of dialysis
      access. This study aimed to compare the primary patency of the treatment area and
      access circuit between stent grafts and angioplasty in dialysis access failure.
      MATERIALS AND METHODS: Three electronic databases, namely, PubMed, Cochrane
      Library of Systematic Reviews, and EMBASE, were searched from the database
      inception to September 2017 without language restriction. Randomized controlled
      trials comparing the primary patency of the treatment area and access circuit
      between stent graft and angioplasty were included. Two independent reviewers
      assessed the quality of the trials and extracted relevant data. RESULTS: Four
      trials satisfied our inclusion criteria. Our pooled results suggested that stent
      graft placement was associated with significantly higher primary patency of
      treatment area (hazard ratio: 0.65, 95% confidence interval: 0.55-0.77, P <
      0.0001, I2 = 0) and access circuit (hazard ratio: 0.76, 95% confidence interval:
      0.65-0.88, P = 0.0004, I2 = 0) in hemodialysis access compared with those of
      standard angioplasty. CONCLUSIONS: The patency of hemodialysis access may be
      higher after stent graft placement combined with standard angioplasty than after
      angioplasty alone.

PMID- 29661294
TI  - Serum lactate predicts resource utilization, but not surgical need, in the
      emergency department.
AB  - BACKGROUND: Serum lactate is frequently tested in the emergency department (ED)
      setting to diagnose visceral ischemia and as a marker of end-organ perfusion. It
      is highly nonspecific, and levels can be affected by both kidney and liver
      function. In this retrospective chart review, we aim to demonstrate that serum
      lactate is overused in the ED setting and predicts resource utilization but not
      the need for surgical intervention. METHODS: ED records with a chief complaint of
      "abdominal pain" were queried for the preceding 12 mo. We excluded pregnant
      patients, patients aged less than 18 years, and patients for whom a blood count
      and chemistry were not obtained. Vital signs, laboratory values, resource
      utilization, and outcome of the visit were obtained. Logistic regression models
      were developed to correct for confounding associations. RESULTS: A total of 1003
      records were obtained initially with 753 patients (75%) included in the study.
      Serum lactate was drawn in 118 patients (15%) and was elevated in 19 patients
      (16% of those drawn). Utilization of computed tomography imaging was associated
      with lactate utilization (P < 0.001). Patients in whom lactate was drawn were
      more likely to have a general surgery consult (51% versus 34%, P < 0.001) and to
      be admitted to the hospital (P < 0.001). CONCLUSIONS: The use of serum lactate in
      the workup of patients with abdominal pain should be targeted at patients who
      have signs of sepsis and based on the index of suspicion for specific disease
      processes such as mesenteric ischemia.

PMID- 29661295
TI  - Quality of life in thyroid cancer-assessment of physician perceptions.
AB  - BACKGROUND: Thyroid cancer is the fastest growing malignancy in the United
      States. Previous studies have shown a decrease in quality of life (QoL) after the
      treatment of thyroid cancer. To date, there have been no studies assessing
      physician perceptions regarding how a diagnosis of thyroid cancer affects QoL.
      Based on this and other findings from our study, we aim to assess physician
      perceptions on the effect of thyroid cancer on QoL. MATERIALS AND METHODS:
      Physicians were recruited from two national organizations comprised physicians
      focusing on thyroid cancer. A 37-question survey was administered evaluating
      physician's perceptions of thyroid cancer patient satisfaction in various aspects
      of treatment, complications, and overall effects on QoL. QoL responses were
      categorized into overall QoL, physical, psychological, social, and spiritual well
      being. RESULTS: One hundred five physicians completed the survey. Physician's
      estimates of patient's overall QoL after thyroid cancer treatment was similar to
      overall QoL reported by patients. However, medical physicians overestimated the
      decrease in thyroid cancer survivor's QoL in several subcategories including
      physical, psychological, and social (P < 0.05). Both surgeons and medical
      physicians underestimated the percentage of patients with reported symptoms of
      temporary and permanent voice changes, temporary dry mouth, cold/heat
      sensitivity, and temporary and permanent hypocalcemia (P = 0.01-0.04).
      CONCLUSIONS: Physicians have a varied estimation of the detrimental impact of
      thyroid cancer treatment on QoL. In addition, physicians underestimated the
      amount of physical symptoms associated with thyroid cancer treatments. Increased
      physician awareness of the detrimental effects of a thyroid cancer diagnosis on
      QoL should allow for a more accurate conversation about expected outcomes after
      thyroid cancer treatment.

PMID- 29661296
TI  - Structural transformation of crystallized debranched cassava starch during dual
      hydrothermal treatment in relation to enzyme digestibility.
AB  - Structural transformation of crystallized debranched cassava starch prepared by
      temperature cycling (TC) treatment and then subjected to annealing (ANN), heat
      moisture treatment (HMT) and dual hydrothermal treatments of ANN and HMT was
      investigated. The relative crystallinity, lateral crystal size, melting
      temperature and resistant starch (RS) content increased for all hydrothermally
      treated samples, but the slowly digestible starch (SDS) content decreased. The RS
      content followed the order: HMT -> ANN > HMT > ANN -> HMT > ANN > TC,
      respectively. The HMT -> ANN sample showed a larger lateral crystal size with
      more homogeneity, whereas the ANN -> HMT sample had a smaller lateral crystal
      size with a higher melting temperature. After cooking at 50% moisture, the
      increased RS content of samples was observed, particularly for the ANN -> HMT
      sample. These results suggest that structural changes of crystallized debranched
      starch during hydrothermal treatments depend on initial crystalline
      characteristics and treatment sequences, influencing thermal stability, enzyme
      digestibility, and cooking stability.

PMID- 29661297
TI  - Preparation and characterization of nanocomposite films from oil palm pulp
      nanocellulose/poly (Vinyl alcohol) by casting method.
AB  - TEMPO-oxidize nanocellulose (TONC) suspension has been obtained from total
      chlorine free (TCF) oil palm empty-fruit-bunches (OPEFB) pulp using 4-acetamido
      TEMPO (2,2,6,6-tetramethyl piperidin-1-oxyl) mediated oxidation with sodium
      hypochlorite and sodium bromide in water at 25  degrees C and pH 10. TONC
      suspension with varied content from 0.5 to 6% (w/w) reinforced polyvinyl alcohol
      (PVA) polymer based nanocomposite films were prepared by the casting method. The
      structural interaction between the TONC and PVA was characterized by the Fourier
      transform infrared (FT-IR) spectroscopy, nuclear magnetic resonance (NMR)
      spectroscopy, X-ray diffraction (XRD) and scanning electron microscopy (SEM). It
      was found that the 4% (w/w) TONC content reinforced nanocomposite exhibited the
      highest tensile strength and modulus with an increase of 122% and 291%
      respectively, compared to PVA while the elongation at break decreased about
      42.7%. Thermal stability of PVA based nanocomposite films was improved after
      incorporation of TONC. Incorporation of TONC in PVA film increases its
      crystallinity due to strongly linking between the hydroxyl groups of materials
      however considerable decreases beyond 2 wt% loading are observed. TONC
      incorporation beyond 2 wt% also reduces the melting temperature peaks and
      enthalpy of nanocomposite films. FT-IR spectra, NMR and SEM indicate that there
      is interaction between the TONC and PVA.

PMID- 29661298
TI  - Engineering of thermoresponsive gels as a fake metastatic niche.
AB  - Chemoattraction through the CXCR4-CXCL12 axis has been shown to be an important
      mechanism to direct circulating tumor cells toward distant sites. The objective
      of this work was to prepare a fake metastatic niche made up of a gel loaded with
      CXCL12. The gel is designed to create a steep concentration gradient of the
      chemokine in the proximity of the site of administration/injection, aimed to
      divert and capture circulating CXCR4+ tumor cells. To this aim, different
      thermoresponsive gels based on methylcellulose (MC) or poloxamers, loaded with
      CXCL12, with or without hyaluronic acid (HA) were designed and their mechanical
      properties correlated with the ability to attract and capture in vitro CXCR4+
      cells. Results of in vitro cell studies showed that all prepared gels induced CEM
      tumor cell migration whereas only gels based on MC embedded with CXCL12 are able
      to capture them.

PMID- 29661299
TI  - Multi-hierarchical tissue-engineering ECM-like scaffolds based on cellulose
      acetate with collagen and chitosan fillers.
AB  - A novel high-tech composite biomimetic matrixes for a wide range of medical
      purposes were prepared. The structure of scaffolds was inspired by the
      architecture of native decellularized tissue: material consists of a sponge and
      fibrous components of different spatial geometry based on cellulose acetate with
      collagen or chitosan filler. The fibrous component was prepared by
      electrospinning, the sponge - freeze-drying technique. The influence of main
      technological parameters, such as freeze mode, polymer type and concentration,
      etc. on the fiber-sponge architecture and properties was examined. It was shown
      that scaffolds with different types of microstructure can be obtained employing
      this technique. The impregnation of chitosan or collagen filler in fiber matrix
      also significantly improves mechanical properties up to 40 MPa for strength and
      600 MPa for Young's modulus.

PMID- 29661301
TI  - Antifouling zwitterionic dextran micelles for efficient loading DOX.
AB  - Polysaccharides derivatives are typical drug nanocarriers which are nontoxic and
      biodegradable. However, as is the case for all drug delivery systems,
      polysaccharides derivatives have to face the issue of protein fouling. In this
      paper, we present the design and synthesis of carboxybetaine-modified dextran
      polycaprolactone (CB-Dex-PCL) copolymers as doxorubicin (DOX) nanocarriers.
      Results showed that DOX/CB-Dex-PCL micelles exhibited better cumulative release
      at the pH value of 5.2 than at the physiological pH of 7.4, which indicated
      potential applications in killing tumor cells while minimizing the toxicity to
      normal tissues. Additionally, antifouling properties of carboxybetaine
      functionalized dextran micelles were much better than that of unmodified dextran
      for fibrinogen and lysozyme as tested by ITC. Finally, cytotoxicity tests using
      Hela cells showed that CB-Dex-PCL and DOX-loaded micelles exhibited great
      biocompatibility. All the above observations indicated that CB-Dex-PCL micelles
      are potentially excellent drug carriers for the treatment of human cancerous
      tumors.

PMID- 29661300
TI  - Chitosan functionalized poly-epsilon-caprolactone electrospun fibers and 3D
      printed scaffolds as antibacterial materials for tissue engineering applications.
AB  - Tissue engineering (TE) approaches often employ polymer-based scaffolds to
      provide support with a view to the improved regeneration of damaged tissues. The
      aim of this research was to develop a surface modification method for introducing
      chitosan as an antibacterial agent in both electrospun membranes and 3D printed
      poly-epsilon-caprolactone (PCL) scaffolds. The scaffolds were functionalized by
      grafting methacrylic acid N-hydroxysuccinimide ester (NHSMA) onto the surface
      after Ar-plasma/air activation. Subsequently, the newly-introduced NHS groups
      were used to couple with chitosan of various molecular weights (Mw). High Mw
      chitosan exhibited a better coverage of the surface as indicated by the higher N%
      detected by X-ray photoelectron spectroscopy (XPS) and the observations with
      either scanning electron microscopy (SEM)(for fibers) or Coomassie blue staining
      (for 3D-printed scaffolds). A lactate dehydrogenase assay (LDH) using L929
      fibroblasts demonstrated the cell-adhesion and cell-viability capacity of the
      modified samples. The antibacterial properties against S. aureus ATCC 6538 and S.
      epidermidis ET13 revealed a slower bacterial growth rate on the surface of the
      chitosan modified scaffolds, regardless the chitosan Mw.

PMID- 29661302
TI  - Polyethersulfone nanofiltration membrane embedded by chitosan nanoparticles:
      Fabrication, characterization and performance in nitrate removal from water.
AB  - In this research, chitosan nanobiopolymers (CS-NPs) were synthesized using
      tripoly phosphate and transferred into the organic solvent via solvent exchange
      method. Different amounts of chitosan nanopolymers were embedded into the
      polyethersulfone (PES) membrane prepared by phase inversion precipitation method.
      The membranes were employed for nitrate removal from water under various solution
      pHs (4.5, 7.0 and 9.0). Scanning electron microscopy, atomic force microscopy,
      porosity, water contact angle and pure water flux measurements were employed to
      characterize the fabricated membranes. Addition of chitosan nanoparticles into
      the membrane matrix increased the water permeability from 13 for pristine
      membrane to 22 kg/m2 h for modified membrane with 0.2 wt.% nanopolymer. However,
      the application of CS-NPs more than 0.4 wt.% led to membranes with a compact
      matrix and dense structure, thereby reducing water permeation even lower than
      PES. At all tested solution pHs, nitrate removal efficiency was significantly
      improved in comparison with pristine PES at as a result of adsorptive properties
      of chitosan biopolymer. The complete nitrate removal (100%) was achieved at
      acidic pH due to protonation of amine groups of CS-NPs creating positive charge
      on the membrane surface.

PMID- 29661303
TI  - Super water absorbing polymeric gel from chitosan, citric acid and urea:
      Synthesis and mechanism of water absorption.
AB  - A new superabsorbent with maximum water absorption capacity of ~1250 g/g is
      prepared by hydrothermal synthesis from sustainable and biodegradable resources
      such as chitosan, citric acid and urea (denoted as 'CHCAUR'). CHCAUR is
      characterized extensively by various analytical techniques such as PXRD, SSNMR,
      FTIR, and TGA. Pure and saline water absorption study showed that CHCAUR could be
      a better adsorbent compared to the super absorbent polymer (SAP) used in
      commercial diaper material. The mechanism of water absorption is shown to arise
      out of a combination of electrostatic attraction of water to the ionic crosslinks
      and the presence of macropores as well as undulated surface due to the formation
      of nanofibrous bundles. When applied to soil CHCAUR was found to decrease water
      evaporation rate significantly.

PMID- 29661304
TI  - Preparation of nano-sized particles from bacterial cellulose using
      ultrasonication and their characterization.
AB  - As more applications for nano-sized natural particles are discovered, simple,
      environmentally friendly ways to produce these particles become more important.
      This work prepares and characterizes nano-size bacterial cellulose particles
      using ultrasonication. Pellicle from nata de coco containing nanofibers was
      broken up in an electrical blender, then sonicated using an ultrasonic probe at
      20 kHz and 3 W/mL for 30, 60 and 90 min. Transmission electron microscope
      observations indicate the particles become nano-sized after 60 min ultrasound.
      The maximum decomposition temperature before sonication was 373  degrees C,
      decreased to 357  degrees C after 60 min ultrasonication. Moisture absorption of
      the 90 min sonicated particles film is 60% slower compared to non-sonicated
      particles. After ultrasonication, the crystallinity index of the cellulose
      decreases. The functional groups of non-sonicated and sonicated cellulose remain
      the same. This study promotes a potential method of fabrication of nano-sized
      particles from pure bacterial cellulose.

PMID- 29661305
TI  - Bio-inspired hydrophobic modification of cellulose nanocrystals with castor oil.
AB  - This work presents an efficient and environmentally friendly approach to generate
      hydrophobic cellulose nanocrystals (CNC) using thiol-containing castor oil (CO
      SH) as a renewable hydrophobe with the assist of bio-inspired dopamine at room
      temperature. The modification process included the formation of the polydopamine
      (PDA) buffer layer on CNC surfaces and the Michael addition reaction between the
      catechol moieties of PDA coating and thiol groups of CO-SH. The morphology,
      crystalline structure, surface chemistry, thermal stability and hydrophobicity of
      the modified CNC were charactered by TEM, XRD, FT-IR, solid-state 13C NMR, XPS,
      TGA and contact angle analysis. The modified CNC preserved cellulose
      crystallinity, displayed higher thermal stability than unmodified CNC, and was
      highly hydrophobic with a water contact angle of 95.6 degrees . The simplicity
      and versatility of the surface modification strategy inspired by adhesive protein
      of mussel may promote rapid development of hydrophobic bio-based nanomaterials
      for various applications.

PMID- 29661306
TI  - Copper-loaded nanocellulose sponge as a sustainable catalyst for regioselective
      hydroboration of alkynes.
AB  - It is desirable for catalyst supports to be biodegradable, easily-modifiable, and
      possessing high surface area. In this work, thiolated nanocellulose sponge was
      prepared from hydrolytic silane condensation of cellulose nanofibrils (CNF) and
      used as a green support to immobilize copper cations via in situ CuII to CuI
      reduction and complexation. The sponge featured high porosity (90.5%) and low
      density (29.4 mg/cm3) with regular morphology. The sponge easily recovered 94% of
      its original shape in water after experiencing 80% deformation under stress of 95
      kPa. When used in catalyzing hydroboration of alkynes, excellent conversion and
      up to 99% regioselectivity were achieved with the copper-loaded sponge. The
      sponge-supported catalysts worked well in the absence of additional ligands, had
      a broad substrate scope, and retained 93% of their activity after six catalytic
      cycles. This simple and scalable strategy offers an efficient route for
      immobilizing metal catalysts on porous supports.

PMID- 29661307
TI  - Effect of pH and precursor salts on in situ formation of calcium phosphate
      nanoparticles in methylcellulose hydrogel.
AB  - Thermo-reversible hydrogels have been widely studied in biomedical research
      fields, because of their potential performance in drug delivery and tissue
      engineering. In this study, a novel thermo-sensitive methylcellulose (MC)
      hydrogel based on calcium phosphate nanoparticles (CaP NPs) was prepared by in
      situ formation process in which precursor salts induced a salt-out effect in the
      MC solution. Based on the Hofmeister series, CaCl2, Na2HPO4, and NaH2PO4
      precursor salts with a good salt-out effect were used as the precursor salts for
      CaP NPs. The gelation of MC solution was accelerated by the salt addition, and
      its effect varied with the salt type. When CaP precursor salts with two different
      Ca/P ratios (0.8/1 and 1.6/1) were added into the MC solution, more elastic MC
      hydrogel was formed at 1.6/1 Ca/P ratio. The CaP NPs were rectangular in shape
      (40-50 nm), and evenly distributed in the MC gel. The X-ray diffraction (XRD)
      observation indicates that dicalcium phosphate dehydrate (DCPD) and octacalcium
      phosphate (OCP) were synthesized at 0.8/1 Ca/P ratio, whereas DCPD was
      synthesized at 1.6/1 Ca/P ratio. This indicates that the CaP NPs with different
      crystalline phases were in situ synthesized in accordance with the Ca/P ratio and
      pH condition (pH 7.4, 9.0). Moreover, the DCPD and OCP crystalline phases were
      converted to the hydroxyapatite (HAP) crystalline phase, as the pH was changed to
      alkaline region. Therefore, the resulting MC composite hydrogel containing HAP
      NPs will be suitable for bone regeneration as an injectable hydrogel.

PMID- 29661308
TI  - Excellent reusable chitosan/cellulose aerogel as an oil and organic solvent
      absorbent.
AB  - Absorption is one of the most important methods for oil spill cleanup. An ideal
      absorbent is expected to possess advantages of low cost, green, high absorption
      capacity and excellent reusability. In this paper, a new kind of cellulose
      aerogel was successfully fabricated via cellulose oxidation, crosslinking, freeze
      drying and cold plasma modification. The obtained aerogel (water contact angle up
      to 152.8 degrees ) exhibited outstanding oil/water selectivity and high
      absorption capacity (13.77-28.20 g/g) for various oils and organic solvents.
      What's more, this kind of aerogel could be reused by simple compression. The
      absorption-desorption process could be repeated for at least 50 cycles. Through
      the kinetic analysis, it was found that the pseudo-second order model was more
      appropriate for the aerogel's oil absorption process. Owing to its low cost,
      hydrophobicity, high absorption capacity and excellent reusability, this kind of
      aerogel is expected to be used in oils and organic solvents spill cleanup and
      oil/water separation field.

PMID- 29661309
TI  - Protein adsorption onto polysaccharides: Comparison of chitosan and chitin
      polymers.
AB  - Chitosan (CHS) and chitin (CHT) biopolymers have found many applications in the
      field of controlled-release drug delivery systems. Herein, molecular dynamics
      (MD) simulation and binding free energy calculations were used to investigate the
      potentials of CHS and CHT polymers for the controlled release of follicle
      stimulating hormone (FSH). The results indicated that FSH conformation did not
      change in the presence of CHS and CHT. In addition, FSH-polymer interactions
      caused stability of the 310-helix structure of the alpha subunits of FSH
      (FSHalpha). Both the biopolymers interacted with the protein mainly through the
      hydrophobic forces. CHS has more affinity for FSH when compared with CHT.
      Furthermore, in both systems, the affinity of polymers for FSHalpha was more than
      that for beta subunits of FSH (FSHbeta). The results suggested that the
      polysaccharides might improve the controlled-release FSH delivery.

PMID- 29661310
TI  - Preparation and characterization of thermoplastic starch composites with fly ash
      modified by planetary ball milling.
AB  - Thermoplastic starch (TPS) composites were prepared containing different amounts
      of unmodified (UFA) or modified fly ash (MFA) powder. The modification of the fly
      ash was carried out by dry grinding UFA in a planetary ball mill at various
      speeds and grinding times. The particle size of the fly ash was determined with a
      laser particle size analyzer and a scanning electron microscope (SEM). It was
      found that the particle size of the UFA decreased from 59.60 MUm to 13.17 MUm
      after grinding for 1 h at 400 rpm. Both UFA and MFA powder were incorporated in a
      thermoplastic starch. The mechanical properties, water resistance, degradation
      under simulated weathering conditions and thermal properties of the TPS and the
      composites were characterized. The maximum tensile strength (7.78 MPa) was
      obtained in a composite with 2.50% of MFA. This value is about 9 times higher
      than the tensile strength of the TPS and 2 times higher than that of a TPS/UFA
      composite with 15.00% UFA. In addition, composites with MFA showed improved water
      resistance and delayed degradation compared to the TPS and the composites with
      UFA. The presence of UFA or MFA had a slight effect on the thermal stability of
      the samples. However, fly ash promoted the final phase of the thermal
      decomposition of starch indicating a possible catalytic activity.

PMID- 29661311
TI  - Isolation and characterisation of microcrystalline cellulose and cellulose
      nanocrystals from coffee husk and comparative study with rice husk.
AB  - Cellulosic material from coffee husk has not been previously studied despite
      being a potential source of reinforcing agents for different applications. This
      material has been extracted and characterised from coffee husk, in parallel with
      previously studied rice husk. Samples have been analysed as to their ability to
      obtain cellulosic fibres and cellulose nanocrystals (CNC) by applying alkali and
      bleaching treatments and final sulphuric acid hydrolysis. Microstructural changes
      were analysed after treatments, and the size and aspect ratio of CNCs were
      determined. Crystallinity and thermal stability of both materials progressed in
      line with the enrichment in cellulosic compounds. The CNC aspect ratio was higher
      than 10, which confers good reinforcing properties. These were tested in
      thermoplastic starch films, whose elastic modulus increased by 186 and 121% when
      1 wt% of CNCs from rice and coffee husks, respectively, was incorporated into the
      matrix. Coffee husk represents an interesting source of cellulosic reinforcing
      materials.

PMID- 29661312
TI  - Development and characterisation of hybrid polysaccharide membranes for
      dehydration processes.
AB  - The purpose of this work is the development and characterisation of new hybrid
      polysaccharide (FucoPol) membranes. These membranes were prepared by
      incorporation of a SiO2 network homogeneously dispersed by using a sol-gel method
      with GPTMS as a crosslinker silica precursor. They were further crosslinked with
      CaCl2 for reinforcement of mechanical properties and improvement of their
      permeation performance. They were characterised in terms of their structural,
      mechanical and thermal properties. They presented a dense and homogeneous
      structure, resistant to deformation, with a Tg of 43  degrees C and a thermal
      decomposition between 240 and 251  degrees C. The hybrid FucoPol membranes were
      tested for ethanol dehydration by pervaporation and also for nitrogen
      dehydration. They exhibited high water selectivity values, similar to PERVAP(r)
      4101, however they lost their stability when exposed to solutions of 10.0 wt.%
      water in ethanol. In contrast, these membranes were stable when applied in N2
      dehydration, leading to reproducible performance and very high water
      selectivities.

PMID- 29661314
TI  - Study of steam explosion pretreatment and preservation methods of commercial
      cellulose.
AB  - Steam explosion (150-200  degrees C, 5-30 min) was performed on a commercial
      cellulose presented in two configurations (fiberized and compact sheet) and its
      effect on their chemical and physical properties was studied, along with the
      influence of two different preservation methods (acetone drying and freezing)
      after pretreatment. No degradation compounds were produced during pretreatment,
      although solid recovery (RS) decreased with temperature from 90% to 62%. Similar
      particle size and surface conditions (increased porosity) were found for both
      types of pretreated samples despite the extremely different initial
      configuration. Crystallinity diminished for 150  degrees C samples, but 200 
      degrees C pretreatment promoted recrystallization. Pretreatment also reduced
      polymerization degree, although enzymatic accessibility did not improve. Both
      acetone and freezing processes extremely affected cellulose properties. Acetone
      drying counterbalanced crystallinity and enzymatic accessibility variations of
      pretreated samples, while decreasing polymerization degree. Freezing dramatically
      decreased enzymatic accessibility of pretreated samples down to 15.8%.

PMID- 29661313
TI  - Synthesis, physicochemical characterization and biological evaluation of chitosan
      sulfate as heparan sulfate mimics.
AB  - Despite the relevant biological functions of heparan sulfate (HS)
      glycosaminoglycans, their limited availability and the chemical heterogeneity
      from natural sources hamper their use for biomedical applications. Chitosan
      sulfates (ChS) exhibit structural similarity to HSs and may mimic their
      biological functions. We prepared a variety of ChS with different degree of
      sulfation to evaluate their ability to mimic HS in protein binding and to promote
      neural cell division and differentiation. The structure of the products was
      characterized using various spectroscopic and analytical methods. The study of
      their interaction with different growth factors showed that ChS bound to the
      proteins similarly or even better than heparin. In cell cultures, a transition
      effect on cell number was observed as a function of ChS concentration.
      Differences in promoting the expression of the differentiation markers were also
      found depending on the degree of sulfation and modification in the chitosan.

PMID- 29661315
TI  - Starch film-coated microparticles for oral colon-specific drug delivery.
AB  - The aim of this study was to prepare and characterize a novel type of starch
      coated microparticles (MPs) allowing site-specific delivery of bioactives to the
      colon. An oral colon-specific controlled-release system was developed in the form
      of MPs coated with a resistant starch (RS2/RS3) film (RS@MPs) through an aqueous
      suspension coating process. The RS2 was chosen from a high-amylose cornstarch
      with 88.5% digestion resistibility. The RS3 was prepared by a high
      temperature/pressure (HTP) treatment, with the following of enzymatic
      debranching, and retrogradation, resulting in a dramatic increase in enzymatic
      resistance (RS3 content: 76.6%). RS@MPs showed 40.7% of 5-aminosalicylic acid
      release within 8 h. The in vivo study of fluorescein-loaded RS@MPs indicated the
      high acidic and enzymatic resistibility of RS@MPs and a restrained release in the
      upper GIT. Therefore, RS@MPs has revealed to be a high potential system for
      accurately targeting bioactive compound delivery to the colon.

PMID- 29661316
TI  - Mechanically improved polyvinyl alcohol-composite films using modified cellulose
      nanowhiskers as nano-reinforcement.
AB  - Cellulose nanowhiskers (CWs) extracted from cotton fibers were successfully
      modified with distinct anhydrides structures and used as additives in poly(vinyl
      alcohol) (PVA) nanocomposite films. The surface modification of CWs was performed
      with maleic, succinic, acetic or phthalic anhydride to compare the interaction
      and action the carboxylic groups into PVA films and how these groups influence in
      mechanical properties of the nanocomposites. CWs presented a high degree of
      crystallinity and good dispersion in water, with average length at the nanoscale.
      The addition of specific amounts (3, 6 and 9 wt.%) of modified-CWs increased up
      to 4.4 times the storage modulus (PVA88-CWSA 9 wt.%), as observed from dynamic
      mechanical analysis (DMA), compared to the bare PVA films. A significant increase
      in mechanical properties such as tensile strength, elastic modulus, and
      elongation at break showed a close relationship to the amount and chemical
      surface characteristics of CWs added, suggesting that these modified-CWs could be
      explored as reinforcement additives in PVA films.

PMID- 29661317
TI  - A beta-glucan from Durvillaea Antarctica has immunomodulatory effects on RAW264.7
      macrophages via toll-like receptor 4.
AB  - We studied the mechanisms underlying the immunostimulatory effects of abeta
      1,3/1,6-glucan (BG136) from Durvillaea Antarctica. Our data showed that BG136
      promoted the activation of MAPKs and NF-kappaB signaling pathways and cytokines
      production. BG136 did not increase MCP-1 or NO production or phosphorylation of
      NF-kappaB and MAPK in TLR4 siRNA knockdown cells, indicating that BG136 activates
      macrophages through TLR4. Flow cytometry analysis and confocal experiment showed
      that BG136 bound to TLR4 expressed on RAW264.7 macrophage cells surface. The
      affinity of BG136 for TLR4 was determined using Surface Plasmon Resonance (SPR)
      (KD: 4.51 * 10-6M). Altogether, our results showed that BG136 activates RAW264.7
      cells by binding to TLR4 and then triggering TLR4-mediated signaling pathways to
      promote cytokines secretion.

PMID- 29661318
TI  - AgBr and AgCl nanoparticle doped TEMPO-oxidized microfiber cellulose as a
      starting material for antimicrobial filter.
AB  - Present work covers the state-of-art progress in the advanced nanoarchitecture of
      organic-inorganic hybrid material; a starting material for the antimicrobial
      filter. TEMPO-mediated oxidation of microfiber cellulose was carried out to
      introduce the surface active carboxyl groups. Accordingly, qualitative and
      quantitative substitution of a functional group was investigated using FTIR,
      Solid state 13C CP/MAS NMR, and potentiometric titration; the reaction resulted
      to about 21.06% increase in carboxylate content. Further, the microwave
      irradiated (600 W) in-situ synthesis of AgBr and AgCl nanocubes were prepared and
      doped on carboxylated microfiber. The prepared AgBr@TO-MF and AgCl@TO-MF were
      tested using XRD, XPS, SEM and FTIR. With an average size of AgBr and AgCl
      nanocubes of around 200 +/- 28 nm and 116 +/- 10.73 nm. Whereas, AgBr@TO-MF and
      AgCl@TO-MF shown excellent antimicrobial activity against E. Coli and B.
      Subtilis, with MIC at around 200 MUg/mL and 150 MUg/mL, respectively.
      Fascinatingly, ICP-OES analysis estimated the silver leached was around 0.1 ppm.

PMID- 29661319
TI  - Fabrication of (PPC/NCC)/PVA composites with inner-outer double constrained
      structure and improved glass transition temperature.
AB  - Improving glass transition temperature (Tg) and mechanical property of the
      environment-friendly poly(propylene carbonate) via intermacromolecular
      complexation through hydrogen bonding is attractive and of great importance. A
      novel and effective strategy to prepare (polypropylene carbonate/nanocrystalline
      cellulose)/polyvinyl alcohol ((PPC/NCC)/PVA) composites with inner-outer double
      constrained structure was reported in this work. Outside the PPC phase, PVA, as a
      strong skeleton at microscale, could constrain the movement of PPC molecular
      chains by forming hydrogen bonding with PPC at the interface of PPC and PVA
      phases; inside the PPC phase, the rod-like NCC could restrain the flexible
      molecular chains of PPC at nanoscale by forming multi-hydrogen bonding with PPC.
      Under the synergistic effect of this novel inner-outer double constrained
      structure, Tg, mechanical properties and thermal stability of (PPC/NCC)/PVA
      composite were significantly increased, e.g. Tg of the composite researched the
      maximum value of 49.6  degrees C, respectively 15.6  degrees C, 5.7  degrees C
      and 4.2  degrees C higher than that of PPC, PPC/NCC and PPC/PVA composite.

PMID- 29661320
TI  - Thermoplastic blends of chitosan: A method for the preparation of high thermally
      stable blends with polyesters.
AB  - Chitosan is high potential material for new applications due to its properties,
      especially its antimicrobial activity, and because it is one of the most abundant
      natural polymers. However, chitosan can be processed only from solution limiting
      its applications. Methods for processing chitosan in molten have been a subject
      of recent interest. One method, involves thermoplastic its blends with poly(vinyl
      alcohol), however these blends undergo degradation due to acid residues from
      previous processing steps. Here we described a process to produce thermoplastic
      blends of poly(vinyl alcohol)-chitosan in a poly(lactic acid) matrix by avoiding
      degradation even at higher chitosan contents. The process involves the use of
      spray- and freeze-drying techniques to produce acid free blends of PVA/chitosan,
      then incorporated in PLA matrix by extrusion. These findings are expected to
      contribute to increasing and extending the applications of polysaccharides, such
      as chitosan, in new applications such as textiles, medical and food packing.

PMID- 29661321
TI  - Sulfation degree not origin of chondroitin sulfate derivatives modulates
      keratinocyte response.
AB  - Chondroitin sulfate (CS) sulfation-dependently binds transforming growth factor
      beta1 (TGF-beta1) and chronic wounds often accompany with epidermal
      hyperproliferation due to downregulated TGF-beta signaling. However, the impact
      of CS on keratinocytes is unknown. Especially biotechnological-chemical
      strategies are promising to replace animal-derived CS. Thus, this study aims to
      evaluate the effects of CS derivatives on the interaction with vascular
      endothelial growth factor-A (VEGF-A) and on keratinocyte response. Over-sulfated
      CS (sCS3) interacts stronger with VEGF-A than CS. Furthermore, collagen coatings
      with CS variants are prepared by in vitro fibrillogenesis. Stability analyses
      demonstrate that collagen is firmly integrated, while the fibril diameters
      decrease with increasing sulfation degree. CS variants sulfation-dependently
      decelerate keratinocyte (HaCaT) migration and proliferation in a scratch assay.
      HaCaT cultured on sCS3-containing coatings produced increased amounts of solute
      active TGF-beta1 which could be translated into biomaterials able to decrease
      epidermal hyperproliferation in chronic wounds. Overall, semi-synthetic and
      natural CS yield to comparable responses.

PMID- 29661322
TI  - Cellulose nanofibers isolated by TEMPO-oxidation and aqueous counter collision
      methods.
AB  - In this research, cellulose nanofiber (CNF) was isolated by the combination of
      chemical 2,2,6,6-tetramethylpiperidine-1-oxylradical (TEMPO)-oxidation and
      physical aqueous counter collision (ACC) methods The combination of TEMPO
      oxidation and ACC is an efficient method to isolate CNFs by reducing chemical
      usage in TEMPO-oxidation and saving energy in ACC along with controlling the size
      of CNFs. Two cellulose sources, hardwood bleached kraft pulp (HW) and softwood
      bleached kraft pulp (SW), were used for the CNF isolation with different TEMPO
      oxidation time and a defined number of ACC pass. The CNF properties were
      investigated and compared in term of morphology, crystallinity index,
      transparency and birefringence. The width of the isolated CNFs from HW is in the
      range of 15.1 nm-17.5 nm, and that of the SW CNFs is between 18.4 nm and 22 nm
      depending on the TEMPO oxidation time. This difference is due to the fact that SW
      is less oxidized than HW under the same chemical dosage, which results in larger
      width of SW-CNFs than HW-CNFs. The HW-CNF treated with TEMPO for over 2 h and
      isolated using ACC with 5 pass offers almost 90% transparency. Birefringence of
      CNFs exhibits that HW-CNFs show better birefringence phenomenon than SW-CNFs. The
      combination of TEMPO-oxidation and ACC methods is useful for isolating CNFs with
      its size control.

PMID- 29661324
TI  - Adsorption study of methyl orange by chitosan/polyvinyl alcohol/zeolite
      electrospun composite nanofibrous membrane.
AB  - The chitosan/polyvinyl Alcohol/zeolite electrospun composite nanofibrous membrane
      was fabricated for adsorption of methyl orange. The EDX, TGA and tensile test
      were carried out for the characterization of the membrane. The Young's Modulus of
      the nanofibrous membranes increased by more than 100% with the addition of
      zeolite to chitosan/PVA. The batch adsorption tests were conducted by varying the
      initial concentration of methyl orange, contact time and pH of the dye solution.
      UV-vis results showed that most of the dye was adsorbed within 6 min. An
      adsorption kinetic study was carried out using the pseudo-second-order kinetic
      model, Lagergren-first-order model and intra particle diffusion model. The
      adsorption kinetics obeyed the Pseudo second order model. The adsorption
      mechanism was analyzed using the Langmuir and Freundlich isotherm model. The
      experimental data fits well with the Freundlich model. The adsorption capacity of
      the membrane was 153 mg/g. Adsorption capacity was decreased with increasing pH
      value. The resulting nanofiber became less active over methyl orange after
      several runs.

PMID- 29661323
TI  - Carboxymethyl guar gum synthesis in homogeneous phase and macroporous 3D
      scaffolds design for tissue engineering.
AB  - Guar gum (GG) is a galactomannan obtained directly from the Cyamopsis
      tetragonoloba seeds pericarb. The biopolymer hydrates hugely in three chain
      associated coil formations. Chaotropic Hofmeister ion like lithium interacts at
      the hydrogen bonding sites and render GG homogenization in polar solvents like
      dimethyl sulfoxide. This phenomenon was used for the first time for galactomannan
      derivatisations in homogeneous phase. Higher degree of substitution (DS) that was
      hereto unattainable in GG was achieved due to Hofmeister ion assisted assembly
      deformations. Furthermore, carboxymethyl guar gum (CMGG, DS = 1.10) blends well
      in poly-vinyl alcohol (PVA) at 2:1 mass ratio and enabled hydrophilic porous
      scaffold design for cell propagation. CMGG-PVA scaffolds porosity was 70-90% and
      the tensile strength was 6.32 MPa. CMGG-PVA scaffolds were useful as cell
      factories and in tissue engineering. New generation guar gum derivative scaffolds
      were non cytotoxic and permitted cell propagation in growth medium.

PMID- 29661326
TI  - Superhydrophobic three-dimensional porous ethyl cellulose absorbent with
      micro/nano-scale hierarchical structures for highly efficient removal of oily
      contaminants from water.
AB  - The development of efficient absorbent materials is of global importance for oil
      spillage cleanup and environmental protection. In this work, a novel
      superhydrophobic micro/nano-scale hierarchical structured ethyl cellulose sponge
      was successfully fabricated via an eco-friendly salt-templating method followed
      by immobilizing silver nanoparticles on the surface and subsequent modification
      with long-chain alkanethiols. The as-prepared sponge with unique micro-nano
      structure and porous interconnected network exhibited low density (<17 kg m-3),
      high porosity (>98%) and robust superhydrophobicity (thetawater = 161.3 degrees ,
      thetaoil = 0 degrees , sliding angle = 3.6 degrees ). The sponge could collect a
      wide range of organic solvents and oils with absorption capacity of 36-48 times
      of its own weight. Furthermore, the absorption capacity decreased slightly to
      89.8% of its initial value after 50 cycles, demonstrating excellent recyclability
      of the sponge. It was believed that the superhydrophobic/superoleophilic sponge
      would be a promising absorbent material for the selective oil removal and
      recovery in environmental remediation.

PMID- 29661325
TI  - Preparation of the chitosan/poly(glutamic acid)/alginate polyelectrolyte
      complexing hydrogel and study on its drug releasing property.
AB  - In the current study, a novel semi-dissolution/acidification/sol-gel transition
      (SD-A-SGT) method was explored for the preparation of polyelectrolyte complexing
      (PEC) composite hydrogels with natural polymers only. A chitosan (CS) powder was
      uniformly dispersed in a solution of poly(glutamic acid) (PGA) and alginate (SA)
      to form a semi-dissolved slurry mixture that was then exposed to an gaseous
      acidic atmosphere. CS was gradually dissolved and interacted with PGA and SA to
      form a CS/PGA/SA PEC composite hydrogel with a homogeneous structure. The SD-A
      SGT procedure was able to overcome the shortcomings of direct mixing method via
      the PEC interaction. The effects of the hydrogel composition on its structure and
      properties were investigated by FTIR, XRD, rheology study, XPS, SEM, and swelling
      kinetics. The drug delivery performance of the CS/PGA/SA hydrogel was explored
      using piroxicam (PXC) as a model drug. PXC was in situ embedded in the hydrogel
      by the SD-A-SGT method. The hydrogel exhibited pH responsive drug release
      behaviors that were affected by the hydrogel composition. In all, the SD-A-SGT
      method for preparing PEC composite hydrogels has a great application potential in
      constructing the CS based hydrogels as medical materials.

PMID- 29661327
TI  - Enzymatic biopolishing of cotton fabric with free/immobilized cellulase.
AB  - Cotton fabric was biopolished using free and immobilized cellulase. The
      immobilized cellulase treatment results lower weight loss and minimum reduction
      in tensile strength of the fabric at the minimum of 67% and a maximum of 98.35%
      and better whiteness index when compared with free cellulase treatment.
      Regression analysis was carried out for all properties, regression coefficients
      and summary of fit have been discussed. Both free and immobilized cellulase
      treated fabrics showed improved crystallinity index and it was analyzed by XRD.
      FTIR spectra were obtained to measure the hydrogen bonding intensity, which
      showed that the intensity values were decreased after treatment. The study
      confirms that the treatment with immobilized cellulase improves the surface
      properties without affecting the strength of fabric than the fabric treated with
      free cellulase.

PMID- 29661328
TI  - Are two laws better than one in Italy? Compulsory vaccinations, double trouble.

PMID- 29661329
TI  - Hearing Loss in the Elderly.
AB  - Presbycusis, or age-related hearing loss (ARHL), is the result of physiologic and
      pathologic changes associated with advancing age. ARHL presents typically with a
      high-frequency hearing loss, which contributes to greater trouble hearing
      consonants within words. Consonants convey the bulk of meaning within a word, and
      this loss of linguistic information results in complaints associated with ARHL.
      Hearing aids and cochlear implants significantly improve the lives of older
      adults with hearing loss, in particular, those with depression and dementia.
      Successful current research in gene therapy, pharmacotherapy, and stems cells
      holds the promise of being able to restore native cochlear function.

PMID- 29661330
TI  - Balance Disorders in Older Adults.
AB  - Balance disorders are common in the elderly and can lead to falls, with resultant
      severe morbidity and even mortality. Progressive loss of vestibular function
      begins in middle age and is affected by multiple disease processes. Polypharmacy
      impacts many disease processes in the elderly, with balance function being one of
      the most susceptible. Evaluation of the older patient with a balance disorder is
      critical for the well-being of these patients, as it may drive intervention. This
      article reviews balance disorders often encountered in older patients and makes
      recommendations regarding education of nonotolaryngologists.

PMID- 29661331
TI  - Geriatric Dysphagia.
AB  - Geriatric dysphagia is an unrecognized and underdiagnosed problem with
      significant morbidity and potential mortality. It requires diligence by the
      clinician and a team approach for successful management. Careful history-taking
      is the key in the treatment of these patients and determines further workup, as
      well as treatment.

PMID- 29661332
TI  - Voice Disorders in the Elderly.
AB  - Presbyphonia is more common than appreciated by most physicians, and it is
      associated with undesirable vocal characteristics such as hoarseness, weakness,
      breathiness, instability, and tremulousness. Hearing impairment in the patient or
      his or her friends, family, and associates exacerbates the problem, resulting in
      depression and social withdrawal, further reducing quality of life. Moreover,
      voice weakness and instability are all too often misinterpreted as reflecting
      intellectual instability. Expert diagnosis, medical treatment, voice therapy and
      training, and occasionally surgery usually can maintain or restore vocal
      stability and "youth."

PMID- 29661333
TI  - Sleep Disorders in the Elderly.
AB  - Although some physiologic changes in sleep are a normal part of the aging
      process, other sleep complaints made by elderly patients can indicate a primary
      or secondary sleep disorder. It is important to recognize the difference between
      normal age-related changes and what may require further testing to make an
      accurate diagnosis. Proper diagnosis and treatment of sleep disorders can improve
      the quality of life and safety for the elderly and their families.

PMID- 29661334
TI  - Rhinosinusitis and Allergies in Elderly Patients.
AB  - The sinonasal tract plays important roles in respiration, olfaction, and defense
      against external pathogens. Like many organ systems, the nose and sinuses undergo
      several changes with advancing age that can play a role in the development of
      disease. This article discusses the physiology of the aging sinonasal tract and
      reviews the common diseases affecting older patients, such as rhinitis and
      rhinosinusitis.

PMID- 29661335
TI  - Head and Neck Cancer in the Elderly: Frailty, Shared Decisions, and Avoidance of
      Low Value Care.
AB  - Head and neck cancer (HNC) is a disease of older adults. Recurrent and metastatic
      head and neck squamous cell carcinoma portends a poor prognosis, with median
      overall survival of less than 12 months. Within this vulnerable population,
      significant treatment-related toxicities and physical and psychosocial sequelae
      can be devastating to quality of life at the end of life. Shared decision making
      and early comprehensive palliative and support services are at the crux of the
      approach to older adults with HNC. In doing so, low-value care that fails to meet
      the goals of patients and their caregivers at the end-of-life may be avoided.

PMID- 29661336
TI  - Cutaneous Head and Neck Malignancies in the Elderly.
AB  - Cutaneous malignancy of the head and neck affects a large proportion of elderly
      patients. The severity ranges from small, easily treatable lesions to large,
      invasive, potentially metastatic tumors. Surgical treatment is the primary
      treatment of most skin cancers; however, geriatric patients are more likely to
      have multiple comorbidities that increase the risk of surgery. Multiple treatment
      modalities exist, including surgical, radiation, and medical therapy.
      Recommendations and treatment options for basal cell carcinoma, squamous cell
      carcinoma, Merkel cell carcinoma, and melanoma are outlined and reviewed.

PMID- 29661337
TI  - Thyroid Disorders in the Elderly: An Overall Summary.
AB  - Medical care for elderly patients is often distinctly different from that of
      younger counterparts. This is no truer than in a thyroid disorder context, where
      patients are often asymptomatic and polypharmacy is a potential consideration.
      Understanding how treatment of these patients can deviate from common practices
      is an essential asset to any health care provider. The purpose of this article is
      to shed light on those deviations and address inherent complexities in caring for
      elderly patients in an effort to improve quality of care. Topics considered range
      from general anatomic challenges to underlying biochemistry to adjuvant therapy
      options and surveillance.

PMID- 29661338
TI  - Anesthesia in the Elderly Patient Undergoing Otolaryngology Head and Neck
      Surgery.
AB  - Geriatric patients undergoing surgery have a whole set of specific physiologic
      changes, perioperative needs, and postoperative complications. This review
      presents an overview of the basic concepts and the evolving challenges pertaining
      to the care of geriatric patients undergoing otolaryngologic procedures from the
      perspective of the anesthesiologist.

PMID- 29661339
TI  - Frailty and Polypharmacy in Older Patients with Otolaryngologic Diseases.
AB  - Frailty and Polypharmacy commonly impact disease processes and treatment of
      patients with otolaryngologic disorders. Although well known to geriatricians,
      the 2 concepts often elude other physicians, including otolaryngologists. This
      article reviews the common manifestations likely to be encountered in
      otolaryngology patients, reviews frailty measures in surgical patients, and makes
      recommendations regarding education of nongeriatricians.

PMID- 29661340
TI  - Geriatric Otolaryngology: Why It Matters.

PMID- 29661341
TI  - Coronary Atherosclerosis: What Do The Lungs Have To Do With It?

PMID- 29661342
TI  - Can Focal Segmental Glomerulosclerosis Be Differentiated From Minimal Change
      Nephrotic Syndrome Using Biomarkers?

PMID- 29661343
TI  - Reduced Forced Expiratory Volume in 1 Second Percentage Predicted Is Associated
      With Diffuse Coronary Atherosclerosis in Hospitalized Patients Undergoing
      Coronary Angiography.
AB  - BACKGROUND: Reduced forced expiratory volume in 1 second percentage (FEV1%)
      predicted is closely related to cardiovascular mortality. However, evidence
      regarding the correlation between FEV1% predicted and the severity of coronary
      atherosclerosis observed on coronary angiography is still limited. We aimed to
      explore whether a decline in FEV1% predicted was associated with diffuse coronary
      atherosclerosis in hospitalized patients. METHODS: A cross-sectional study
      enrolling hospitalized patients with cardiovascular symptoms undergoing both
      coronary angiography and lung function testing was conducted. The correlation
      between FEV1% predicted and angiographic characteristics, including the number of
      diseased vessels, total number of coronary lesions and Gensini score was
      analyzed. RESULTS: Eighty-five patients were included. Patients with >=2-vessel
      disease had significantly lower FEV1% predicted than patients with <2-vessel
      disease (60.9% +/- 19.7% versus 77.2% +/- 19.7%, P < 0.001). FEV1% predicted was
      inversely related to the total number of coronary lesions (beta = -0.029, P =
      0.002) and Gensini score (beta = -0.525, P = 0.006). FEV1% predicted was
      independently associated with >=2-vessel disease (odds ratio = 0.961, P = 0.007),
      total number of coronary lesions (adjusted beta = -0.039, P < 0.001) and Gensini
      score (adjusted beta = -0.602, P = 0.005) after adjustment for other traditional
      cardiovascular risk factors. In the coronary artery disease subgroup, FEV1%
      predicted maintained an independent and negative relationship with >=2-vessel
      disease, total number of coronary lesions and Gensini score. CONCLUSIONS: Reduced
      FEV1% predicted was closely associated with multivessel coronary disease and
      diffuse coronary atherosclerosis in hospitalized patients undergoing coronary
      angiography.

PMID- 29661344
TI  - Clinical Significance of Urinary Biomarkers in Patients With Primary Focal
      Segmental Glomerulosclerosis.
AB  - BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is often accompanied with
      tubulointerstitial lesion. This study aimed to assess the role of urinary
      biomarkers in predicting tubulointerstitial lesion and treatment response in FSGS
      patients. METHODS: Urinary neutrophil gelatinase-associated lipocalin (NGAL),
      kidney injury molecule-1 (KIM-1), N-acetyl-beta-d-glucosaminidase (NAG) and
      retinol-binding protein (RBP) were measured in 32 FSGS patients and 22 patients
      with minimal change nephrotic syndrome. Patients with FSGS were followed up to
      investigate the value of these markers in predicting treatment response. RESULTS:
      FSGS patients had higher urinary NGAL, NAG and RBP than patients with minimal
      change nephrotic syndrome with comparable proteinuria. A cutoff value of
      15.87ng/mL NGAL demonstrated 87.1% sensitivity and 59.1% specificity for the
      diagnosis of FSGS, with an area under the receiver operator characteristic curve
      of 0.801. In FSGS, these markers correlated significantly with the degree of
      acute tubulointerstitial damage but not with chronic tubulointerstitial lesion.
      Response to immunosuppressive therapy was significantly different in patients
      with KIM-1, NAG and RBP levels below and above the cutoff values. CONCLUSIONS:
      Urinary NGAL, KIM-1, NAG and RBP are reliable biomarkers of tubulointerstitial
      lesion in FSGS patients. The measurements of these markers may be useful in
      diagnosing FSGS, detecting acute tubulointerstitial lesion and predicting
      treatment response.

PMID- 29661345
TI  - DASS21: A Useful Tool in the Psychological Profile Evaluation of Dialysis
      Patients.
AB  - BACKGROUND: The effect of dialysis treatment is complex, with both clinical and
      socio-psychological effects. In this study, we aimed to assess the psychological
      status of this growing population of end-stage renal disease. METHODS: Using the
      Short Form of Depression, Anxiety and Stress Scale (DASS21) questionnaire, we
      aimed (1) to measure the psychological states of hemodialysis (HD) or peritoneal
      dialysis (PD) subjects from 15 sites, (2) to compare DASS21 scores between HD and
      PD, and (3) to identify the associated demographic and medical factors of better
      psychological states. RESULTS: A total of 1,332 were eligible for analysis.
      Stress (48%) recorded the highest negative emotional states, followed by
      depression (37%) and anxiety (20%). By multivariate analysis, normal body mass
      index weight status, religion and absence of coronary artery disease were
      associated with lower score for depression, anxiety and stress, respectively.
      Tertiary education was associated with the lowest score in depression and
      anxiety, whereas HD had a lower score in stress than PD. A younger age was
      associated with worse DASS21 score of anxiety and stress. CONCLUSIONS: Obesity,
      religion and coronary artery disease were significantly associated with all 3
      symptoms of depression, anxiety and stress. Older age has a protective effect on
      anxiety and stress. Further study is needed to evaluate the relationship between
      these significant factors and each psychological state.

PMID- 29661346
TI  - Drug-Eluting Stents Versus Bare-Metal Stents in Patients With End-Stage Renal
      Disease.
AB  - BACKGROUND: The clinical outcomes of drug-eluting stents versus bare-metal stents
      in end-stage renal disease patients remains controversial. METHODS: A
      comprehensive literature search of Pubmed, Embase and Cochrane Library from
      January 2000 until November 2016 was conducted to identify relevant articles. We
      pooled the odds ratios (OR) from individual studies and conducted heterogeneity,
      quality assessment and publication bias analyses. RESULTS: A total of 18 studies
      with 44,194 patients were identified. Compared with bare-metal stent-treated
      patients, drug-eluting stent-treated patients had significantly lower short-term
      and long-term all-cause mortality (OR = 0.56; 95% CI: 0.48-0.65; P < 0.00001; OR
      = 0.78; 95% CI: 0.66-0.92; P = 0.004, respectively), myocardial infarction (OR =
      0.69; 95% CI: 0.53-0.88; P = 0.003) and major adverse cardiac events (OR = 0.72;
      95% CI: 0.58-0.90; P = 0.004), with no detectable difference regarding stent
      thrombosis (OR = 0.80; 95% CI: 0.43-1.49; P = 0.47), cardiac mortality (OR =
      0.95; 95% CI: 0.89-1.02; P = 0.14) and repeat revascularization (OR = 0.81; 95%
      CI: 0.62-1.06; P = 0.13). CONCLUSIONS: In patients with end-stage renal disease,
      the use of drug-eluting stents could significantly reduce the rates of mortality,
      myocardial infarction and major adverse cardiac events without increased risk of
      stent thrombosis. It poses imperative demands for future prospective randomized
      studies to define the optimal stent choice in this high-risk population.

PMID- 29661347
TI  - Association Between Metabolic Syndrome and Microvascular and Macrovascular
      Disease in Type 2 Diabetic Mellitus.
AB  - BACKGROUND: The prevalence of metabolic syndrome (MetS) in patients with type 2
      diabetes mellitus is high. The aim of this study was to investigate the
      association between MetS and micro- and macrovascular disease in patients with
      diabetes and the associated risk factors. METHODS: The study enrolled 1,986 (854
      men and 1,132 women) patients with type 2 diabetes mellitus from outpatient
      clinics. MetS was defined according to the Adult Treatment Panel III for Asians.
      RESULTS: Of the enrolled patients, 1,363 had MetS and 623 did not. The patients
      with MetS had significantly higher rates of albuminuria (40.8% vs. 21.8%, P <
      0.001), retinopathy (37.9% vs. 28.6%, P < 0.001), coronary artery disease (19.4%
      vs. 11.6%, P < 0.001), cerebrovascular disease (5.8% vs. 3.2%, P = 0.014), and an
      ankle-brachial index < 0.9 or >= 1.3 (6.1% vs. 3.0%, P = 0.015). Moreover, there
      were significant trends for stepwise increases in albuminuria, retinopathy,
      coronary artery disease, cerebrovascular disease and peripheral artery disease
      corresponding to the number of MetS components (all P for trend < 0.05). Risk
      factors including MetS, old age, sex, wide pulse pressure, increased hemoglobin
      A1c, dyslipidemia and decline renal function were associated with micro- and
      macrovascular disease. CONCLUSIONS: MetS and the number of its components were
      significantly associated with micro- and macrovascular disease in the study
      patients with diabetes and this resulted in a higher risk of cardiovascular
      disease. Screening programs to allow for early detection and interventions should
      be established to lower the risk of cardiovascular disease.

PMID- 29661348
TI  - Using Both Lactic Dehydrogenase Levels and the Ratio of Involved to Uninvolved
      Free Light Chain Levels as Risk Factors Improves Risk Assessment in Patients With
      Newly Diagnosed Multiple Myeloma.
AB  - BACKGROUND: This study aimed to evaluate the prognostic value of the ratio of
      involved to uninvolved free light chain (rFLC) levels and lactic dehydrogenase
      (LDH) levels in the risk stratification of patients with multiple myeloma (MM).
      MATERIALS AND METHODS: Clinical data of 283 patients with newly diagnosed MM were
      retrospectively analyzed. RESULTS: In the traditional chemotherapy group,
      patients with an rFLC < 100 had a better prognosis than those with an rFLC >= 100
      (40 months versus 6 months, P = 0.022), as did patients with an LDH <= upper
      limit of normal (ULN) compared to those with an LDH > ULN (29 months versus 6
      months, P = 0.023). In patients who underwent novel drug-combined therapy, no
      significant difference was observed between the rFLC < 100 group and the rFLC >=
      100 group (54 months versus median not reached, P = 0.508). However, patients
      with an LDH <= ULN had a better prognosis than those with an LDH > ULN (60 months
      versus 21 months, P = 0.004). Using an rFLC >= 100 and an LDH >= ULN as adverse
      risk factors, patients were classified into 3 groups: group 1 (no adverse risk
      factors), group 2 (1 adverse risk factor) and group 3 (2 adverse risk factors).
      The median overall survival (OS) of groups 1, 2 and 3 was 52 months, 34 months
      and 15 months, respectively (P = 0.001). CONCLUSIONS: rFLC and LDH levels were
      sensitive prognostic factors in MM patients, combining them could improve the
      risk stratification and treatment choice of patients in clinical practice.

PMID- 29661349
TI  - Clinical Characteristics and Efficacy of Radiofrequency Catheter Ablation in the
      Treatment of Elderly Patients with Atrial Fibrillation.
AB  - OBJECTIVE: This study aims to investigate the clinical characteristics and
      therapeutic effect of radiofrequency catheter ablation (RFCA) in elderly patients
      with atrial fibrillation (AF). MATERIALS AND METHODS: This retrospective study
      included 668 patients with AF who underwent RFCA in our hospital from June 2010
      to June 2015. Patients were divided into 2 groups according to age: group E (>=60
      years old, n = 308) and group N (<60 years old, n = 360). Ablation endpoints
      included the following 3 points: (1) all preset ablation lines were completed;
      (2) all pulmonary veins were electrically isolated; and (3) negative evoked
      results were achieved. The success of follow-up was defined as patients who did
      not have an atrial arrhythmia attack for at least 3 months without the
      administration of antiarrhythmia drugs. RESULTS: Clinical characteristics of
      elderly patients with AF: the proportion accounted for by female patients with
      AF, patients with hypertension, and patients with a CHADS2 score >=2 points was
      significantly higher than that in group N (P < 0.001). RFCA procedure and safety:
      differences in the success rate of the first operation and severe complications
      were not statistically significant (P > 0.05). Postoperative follow-up: the
      follow-up period was between 6 and 12 months after operation. Differences in the
      proportion of patients with repeated ablation and total success rate were not
      statistically significant (P > 0.05). CONCLUSIONS: Although elderly patients with
      AF had more clinical complications, no differences in the success rate of RFCA
      and postoperative complications between the 2 groups were found. RFCA is a safe
      and effective treatment for elderly patients with AF.

PMID- 29661350
TI  - Monocyte Programmed Death Ligand-1, A Predicator for 28-Day Mortality in Septic
      Patients.
AB  - BACKGROUND: Sepsis is a great health burden for millions of people worldwide and
      plays a critical role in the cause of death in intensive care units. Previous
      studies have revealed that programmed cell death 1 (PD-1) and programmed cell
      death ligand 1 (PD-L1) play critical roles in the immunosuppression phase induced
      by sepsis. The objective of this present study was to establish whether PD-1/PD
      L1 expressions were associated with 28-day mortality of septic patients. METHODS:
      Consecutive patients admitted to the intensive care units of Taizhou People's
      Hospital for the treatment of sepsis from June 2014 through June 2016 were
      included. The demographic and clinical characteristics, laboratory tests, PD-1
      and PD-L1 expressions on monocytes/CD4+T/CD8+T cells were compared between
      survivors and nonsurvivors. Univariate and multivariate logistic regression
      analyses were plotted for prognostic factors associated with mortality at day-28
      in septic patients. RESULTS: A total of 177 septic patients were finally admitted
      to this study protocol, including 131 survivors and 46 nonsurvivors with a
      mortality of 26.0%. High PD-L1/monocytes expressions showed an independently
      significant association with 28-day mortality in septic patients (odds ratio:
      4.73, 95% CI: 1.78-15.32, P = 0.033). The receiver operating characteristic curve
      analysis also indicated PD-L1/monocytes as a predicator for 28-day mortality with
      a cutoff value of 45.68%. CONCLUSIONS: Our results suggested monocyte PD-L1
      expression on admission was an independent risk factor for day-28 mortality in
      septic patients.

PMID- 29661351
TI  - Novel Insights Into E3 Ubiquitin Ligase in Cancer Chemoresistance.
AB  - Drug resistance can obstruct successful cancer chemotherapy. The ubiquitin
      proteasome pathway has emerged as a crucial player that controls steady-state
      protein levels regulating multiple biological processes, such as cell cycle,
      cellular proliferation, apoptosis, and DNA damage response, which are involved in
      oncogenesis, cancer development, prognosis, and drug resistance. E3 ligases
      perform the final step in the ubiquitination cascade, and determine which protein
      becomes ubiquitylated by specifically binding the substrate protein. They are
      promising drug targets thanks to their ability to regulate protein stability and
      functions. Although patient survival has increased in recent years with the
      availability of novel agents, chemoresistance remains a major problem in cancer
      management. E3 ligases attract increasing attention with advances in
      chemoresistance knowledge. To explore the role of E3 ligase in cancer
      chemotherapy resistance and the underlying mechanism, we summarize the growing
      number of E3 ligases and their substrate proteins, which have emerged as crucial
      players in cancer chemoresistance and targeted therapies.

PMID- 29661352
TI  - Effects of Alpinetin on Intestinal Barrier Function, Inflammation and Oxidative
      Stress in Dextran Sulfate Sodium-Induced Ulcerative Colitis Mice.
AB  - BACKGROUND: Alpinetin is a flavonoid isolated from Alpinia katsumadai Hayata that
      has demonstrated anti-inflammatory, antibacterial and anti-tumor activities.
      However, alpinetin has not been widely studied in amelioration of inflammatory
      bowel disease. The study aimed to investigate the role of alpinetin on intestinal
      epithelial tight junctions, oxidative stress and Nrf2/HO-1 signaling pathway in
      dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice. METHODS: A
      total of 40 mice were divided into 5 groups (n = 8/group): control group, DSS
      group (received 3% DSS), and low, medium and high-dose treatment groups (3% DSS +
      alpinetin 25, 50 and 100mg/kg). The disease activity index (DAI), histological
      scores, epithelial tight junctions, oxidative stress factors, and Nrf2/HO-1
      signaling pathway in the colon were determined. RESULTS: Alpinetin improved DAI,
      colonic shortening, histological scores and myeloperoxidase activity compared
      with the DSS group. The expression of occludin and zonula occludens-1 were
      upregulated by alpinetin, whereas the expression of claudin-2 was reduced.
      Moreover, alpinetin inhibited the level of malondialdehyde, and increased the
      level of superoxide dismutase. Nrf2/HO-1 signaling pathways were also found to be
      activated. CONCLUSION: Alpinetin is associated with decreased intestinal
      inflammation and oxidative stress dose-dependently, and also regulated the
      expression of tight junctions between cells in UC mice. The findings of our study
      may shed light on the use of alpinetin in the treatment of UC.

PMID- 29661353
TI  - Recurrent Pyroglutamic Acidosis Related to Therapeutic Acetaminophen.
AB  - Pyroglutamic acid, an intermediate in glutathione metabolism, can lead to
      elevated anion gap metabolic acidosis as rare complication of acetaminophen
      therapy in adults. Acquired pyroglutamic acidosis has been observed primarily in
      settings associated with glutathione deficiency. Risk factors for glutathione
      deficiency include critical illness, chronic liver or kidney disease, advanced
      age, female gender, alcohol abuse, malnutrition, pregnancy, antiepileptic drugs,
      and chronic acetaminophen use. Diagnosis of pyroglutamic acidosis requires both
      the exclusion of common etiologies of increased anion gap metabolic acidosis and
      a high index of suspicion. Treatment involves discontinuation of acetaminophen,
      supportive care, and addressing risk factors for glutathione deficiency. The
      current report describes an ambulatory patient with multiple risk factors for
      glutathione deficiency, who developed recurrent pyroglutamic acidosis due to
      acetaminophen use with therapeutic blood levels of acetaminophen.

PMID- 29661354
TI  - Fatal Hypermagnesemia Due to Laxative Use.
AB  - We report a case of fatal hypermagnesemia in a 53-year-old woman admitted for
      acute exacerbation of chronic obstructive pulmonary disease and with a history of
      chronic constipation treated regularly with magnesium-containing laxatives. On
      admission, her magnesium level was 2.0mg/dL, which rose to a peak of 10.8mg/dL
      despite hydration and diuresis in the presence of a normal kidney function.
      Continuous renal replacement therapy was promptly initiated, which reduced her
      serum magnesium levels, but her condition continued to deteriorate precipitously
      progressing to shock leading to oligoanuric renal failure, and she died 2 days
      later. A review of the literature shows that though rare and often unsuspected,
      severe hypermagnesemia frequently results in death even in individuals with
      normal renal function despite renal replacement therapy. In patients with
      constipation, retention of magnesium-based laxative in the gut apparently serves
      as a reservoir for continuous magnesium absorption and contributes to mortality.

PMID- 29661355
TI  - The Structure of Medical Intensive Care Units at Training Institutions.
AB  - BACKGROUND: As a result of the 2011 Accreditation Council for Graduate Medical
      Education (ACGME) work hour guideline implementation, the structure of intensive
      care unit (ICU) teams at training institutions has been affected. The impact
      these changes have had on the current work environment has not been well
      described. METHODS: The authors conducted an online survey of internal medicine
      program directors in 2016. The survey investigated how training institutions
      structure their intensive care units in reference to volume, resident housestaff
      and alternative coverage options, with a focus on changes made after the
      implementation of the 2011 ACGME duty hour restrictions. RESULTS: Notable
      differences were found in program director responses to coverage of patients in
      the ICUs. A total of 62 of the 132 (48%) responding program directors describe
      coverage of all patients solely by resident housestaff. Since 2011, 54 (41%)
      programs have increased the number of resident physicians rotating in the ICU per
      month and initiated or increased the use of nonresident coverage of patients. Use
      of non-resident providers is not associated with a decrease in the number of
      total ICU months per resident or a decrease in educational value. CONCLUSIONS:
      Since the 2011 ACGME duty hour implementation, there is wide variability in the
      learning environment of medical intensive care units in training institutions.

PMID- 29661356
TI  - Shift: A Medical Student's Reflections on the Practice of Medicine and Nursing.

PMID- 29661357
TI  - Prognostic Value of Ventricular Wall Motion Score and Global Registry of Acute
      Coronary Events Score in Acute Mocardial Infarction Patients: Methodological
      Issues.

PMID- 29661358
TI  - Letter to the Editor.

PMID- 29661359
TI  - Infective Endocarditis in the Intravenous Drug User: Treatment Shortcomings.

PMID- 29661360
TI  - Heimlich Maneuver-Induced Diaphragmatic Rupture and Hiatal Hernia.

PMID- 29661361
TI  - The ATTRACTiveness of catheter-directed thrombolysis.

PMID- 29661362
TI  - Invited commentary.

PMID- 29661364
TI  - Invited commentary.

PMID- 29661363
TI  - The effect of commercial insurance policies on outcomes of venous ablation.
AB  - OBJECTIVE: The use of venous ablation (VA) for treatment of chronic venous
      insufficiency has exponentially increased. To limit cost and overuse, insurance
      companies have adopted aleatory policies. The goal of this study was to compare
      the policies of five major local insurance carriers and to determine whether
      treatment within the criteria of a certain policy is associated with improved
      patient outcomes. METHODS: A retrospective single-center review of patients
      treated with VA was performed. Demographics, comorbidities, symptoms, and
      clinical class (Clinical, Etiology, Anatomy, and Pathophysiology classification)
      were recorded. Clinical success was defined on chart review by the patients'
      reporting of improvement or resolution of symptoms in the leg treated on follow
      up, and technical success was defined by vein closure on ultrasound. Patients
      underwent a telephone survey inquiring about intensity of symptoms on a numeric
      rating scale of 0 to 10 before and after treatment of each leg as well as effects
      on quality of life (QOL). The policies of Aetna, Cigna, Anthem Blue Cross Blue
      Shield, UnitedHealthcare, and Connecticut Care were reviewed. The clinical and
      technical success rates were compared when veins were treated within the criteria
      of each policy. A subgroup analysis looking at patients who had clinical success
      only was performed to determine the potential rate of denial of coverage for each
      policy. A multivariable analysis was performed to determine independent
      predictors of clinical success. RESULTS: There were 253 patients with 341 legs
      treated. The mean age was 58.5 +/- 15.2 years (68% women). The most common
      symptom was pain (89.7%), with 47.8% of patients having C3 disease. The clinical
      success, technical success, and complication rates were 84.2%, 95.1%, and 5.6%,
      respectively. On survey, there was improvement of the numeric rating scale score
      in 84.3% of legs treated after the procedure, and 76.7% continued to experience
      improvement after a mean follow-up of 26.8 months. There was improvement of QOL
      in 76.5% of patients. There was no significant difference in procedural success,
      technical success, complication rate, or improvement in QOL when patients were
      treated within any of the five insurance policies. On multivariable analysis,
      there was no single policy significantly associated with clinical success.
      However, subgroup analysis of procedures with clinical success (n = 287) showed a
      significant difference between the five policies on analysis of the potential
      denial of coverage, ranging from 5.6% for Connecticut Care to 64.1% for
      UnitedHealthcare (P < .0001). CONCLUSIONS: The different insurance policies have
      no correlation with outcomes of VA. Policies with more stringent criteria
      typically restrict treatment to larger veins and deny procedures to a significant
      number of patients with chronic venous insufficiency who can benefit from them.

PMID- 29661365
TI  - Invited commentary.

PMID- 29661366
TI  - A systematic review of venous aneurysms by anatomic location.
AB  - OBJECTIVE: Venous aneurysms are uncommon vascular abnormalities that may be
      identified anywhere in the body. Historically, they were often misdiagnosed as
      soft tissue lesions, but with the advent of readily available noninvasive imaging
      (such as duplex ultrasound), they can now be easily identified. Our aim was to
      review the presentation of venous aneurysms, available imaging modalities for
      defining them, and management. METHODS: The English-language literature before
      March 2017 was reviewed, and only reports of primary venous aneurysms of the deep
      veins were included. Reports were subdivided on the basis of the location of the
      venous aneurysm, and reports containing sample imaging studies were referenced
      from Elsevier publications. RESULTS: In total, our review identified reports of
      35 head and neck venous aneurysms, 42 thoracic venous aneurysms, 152 intra
      abdominal venous aneurysms, and 279 venous aneurysms of the extremities. Venous
      aneurysms of the lower extremity deep veins were most likely to be manifested by
      venous thromboembolic events, with approximately 25% to 50% of popliteal vein
      aneurysms presenting with pulmonary embolism. Diagnosis can be made by duplex
      ultrasound, computed tomography venography, magnetic resonance venography, or
      invasive venography. Management varies by location; most thoracic and head and
      neck aneurysms are observed, whereas venous aneurysms of the extremities are
      treated with surgical intervention, given the potential for venous
      thromboembolism. Few reports describe endovascular management of these lesions,
      so open surgical intervention remains the standard of care. CONCLUSIONS: Venous
      aneurysms are rare vascular malformations that occur throughout the body. Many
      are identified on routine imaging ordered for other indications, whereas venous
      aneurysms of the deep veins of the extremities are often manifested with venous
      thromboembolism. Management of these lesions is determined largely by location
      and the potential morbidity and mortality of the untreated aneurysms vs surgery;
      aneurysms of the head and neck and thorax are managed with observation and serial
      imaging over time, whereas those of the abdomen and extremities are treated with
      surgical intervention. Endovascular techniques continue to lack a defined role in
      their management, and the standard of care remains open repair, when indicated.

PMID- 29661367
TI  - Quality Payment Program compliance and vein center acreditation.

PMID- 29661368
TI  - Treatment of incompetent veins of the lower extremities.

PMID- 29661369
TI  - Regarding "Double prepuncture as a valuable adjunctive technique for complex
      endovenous ablation".

PMID- 29661370
TI  - Reply.

PMID- 29661371
TI  - Regarding "The optimal procedure of modified Rex shunt for the treatment of
      extrahepatic portal hypertension in children".

PMID- 29661372
TI  - Reply.

PMID- 29661373
TI  - Regarding "The effect of wavelength on endothermal heat-induced thrombosis
      incidence after endovenous laser ablation".

PMID- 29661374
TI  - Reply.

PMID- 29661375
TI  - [Requirement of DPD deficiency screening before prescription of
      fluoropyrimidines].

PMID- 29661376
TI  - Comparing interventions with network meta-analysis.

PMID- 29661377
TI  - Correspondence: Living systematic reviews.

PMID- 29661378
TI  - Differential role of nitric oxide in the psychedelic symptoms induced by racemic
      ketamine and esketamine in human volunteers.
AB  - BACKGROUND: Animal studies suggest that N-methyl-d-aspartate receptor (NMDAR)
      hypofunction and subsequent decline in intracellular nitric oxide (NO) are
      responsible for development of ketamine-induced psychedelic symptoms. To examine
      this mechanism in humans, we administered the NO donor sodium nitroprusside
      during infusion of racemic ketamine (RS-ketamine), containing equal amounts of
      S(+)- and R(-)-ketamine isomers, or esketamine, containing just the S(+)-isomer.
      METHODS: In this randomised, double blind, placebo-controlled crossover study,
      healthy volunteers were treated with sodium nitroprusside 0.5 MUg kg-1 min-1 or
      placebo during administration of escalating doses of RS-ketamine (total dose 140
      mg) or esketamine (70 mg). Drug high, internal and external perception, obtained
      using the Bowdle questionnaire, were scored over time on a visual analogue scale.
      The area-under-the-time-effect-curve (AUC) was calculated for each end-point.
      RESULTS: Sodium nitroprusside significantly reduced drug high AUC [mean (standard
      deviation); placebo 9070 (4630) vs sodium nitroprusside 7100 (3320), P=0.02],
      internal perception AUC [placebo 1310 (1250) vs nitroprusside 748 (786), P<0.01]
      and external perception AUC [placebo 4110 (2840) vs nitroprusside 2890 (2120),
      P=0.02] during RS-ketamine infusion, but was without effect on any of these
      measures during esketamine infusion. CONCLUSIONS: These data suggest that NO
      depletion plays a role in RS-ketamine-induced psychedelic symptoms in humans. The
      sodium nitroprusside effect was observed for R(-)- but not S(+)-isomer-induced
      psychedelic symptoms. Further studies are needed to corroborate our findings and
      assess whether higher sodium nitroprusside doses will reduce esketamine-induced
      psychedelic symptoms. CLINICAL TRIAL REGISTRATION: NTR 5359.

PMID- 29661379
TI  - Isoflurane disrupts excitatory neurotransmitter dynamics via inhibition of
      mitochondrial complex I.
AB  - BACKGROUND: The mechanisms of action of volatile anaesthetics are unclear.
      Volatile anaesthetics selectively inhibit complex I in the mitochondrial
      respiratory chain. Mice in which the mitochondrial complex I subunit NDUFS4 is
      knocked out [Ndufs4(KO)] either globally or in glutamatergic neurons are
      hypersensitive to volatile anaesthetics. The volatile anaesthetic isoflurane
      selectively decreases the frequency of spontaneous excitatory events in
      hippocampal slices from Ndufs4(KO) mice. METHODS: Complex I inhibition by
      isoflurane was assessed with a Clark electrode. Synaptic function was measured by
      stimulating Schaffer collateral fibres and recording field potentials in the
      hippocampus CA1 region. RESULTS: Isoflurane specifically inhibits complex I
      dependent respiration at lower concentrations in mitochondria from Ndufs4(KO)
      than from wild-type mice. In hippocampal slices, after high frequency stimulation
      to increase energetic demand, short-term synaptic potentiation is less in KO
      compared with wild-type mice. After high frequency stimulation, both Ndufs4(KO)
      and wild-type hippocampal slices exhibit striking synaptic depression in
      isoflurane at twice the 50% effective concentrations (EC50). The pattern of
      synaptic depression by isoflurane indicates a failure in synaptic vesicle
      recycling. Application of a selective A1 adenosine receptor antagonist partially
      eliminates isoflurane-induced short-term depression in both wild-type and
      Ndufs4(KO) slices, implicating an additional mitochondria-dependent effect on
      exocytosis. When mitochondria are the sole energy source, isoflurane completely
      eliminates synaptic output in both mutant and wild-type mice at twice the (EC50)
      for anaesthesia. CONCLUSIONS: Volatile anaesthetics directly inhibit
      mitochondrial complex I as a primary target, limiting synaptic ATP production,
      and excitatory vesicle endocytosis and exocytosis.

PMID- 29661380
TI  - Relationship between severe obesity and depth to the cricothyroid membrane in
      third-trimester non-labouring parturients: a prospective observational study.
AB  - BACKGROUND: Severely obese parturients have increased 'cannot intubate, cannot
      oxygenate' risk during Caesarean section under general anaesthesia. Front-of-neck
      access (FONA) at the cricothyroid membrane (CTM) is definitive management;
      however, attempted FONA can fail. Point-of-care ultrasonography may provide
      useful information about CTM depth to aid FONA in obesity. This study determined
      the difference in CTM depth between severely obese and non-obese parturients,
      utilising ultrasonography. METHODS: In this prospective observational study, two
      anaesthetists performed airway ultrasonography on 15 severely obese (BMI >45 kg m
      2) and 15 normal-weight (BMI <=25 kg m-2) parturients in the third trimester,
      using the transverse and longitudinal planes, sniffing and extended head
      positions, and nil and firm transducer pressures. The primary outcome was CTM
      depth (millimetres) measured in the transverse plane with the head extended and
      nil transducer pressure. Secondary outcomes included CTM depth measurements using
      other factor configurations. Intra-class correlation coefficients assessed the
      inter-observer reliability. RESULTS: CTM depth measured in the transverse plane
      with head extended and nil transducer pressure was significantly greater in
      severely obese parturients, mean 18.0 mm (95% confidence interval 16.3-19.8), vs
      10.6 mm (8.81-12.4) in non-obese (P<0.001); mean difference 7.4 mm (4.9-9.9;
      P<0.001). CTM depths were increased in the severely obese group regardless of
      scanning plane, head and neck position, or transducer pressure (all P<0.001).
      There was excellent inter-observer reliability. CONCLUSIONS: Cricothyroid
      membrane depth is significantly increased in severely obese vs normal-weight
      parturients independently of scanning plane, head and neck position, or
      transducer pressure.

PMID- 29661381
TI  - A review of the safety and efficacy of inhaled methoxyflurane as an analgesic for
      outpatient procedures.
AB  - Methoxyflurane delivered via a hand-held inhaler is a proven analgesic which has
      been used in Australasia for emergency relief of trauma associated pain since the
      1970s. The agent is self-administered by the patient under the supervision of
      trained personnel. More than 5 million patients have received inhaled
      methoxyflurane without significant side effects. Methoxyflurane is also licensed
      in Australasia for the relief of pain in monitored conscious patients requiring
      analgesia for minor surgical procedures. Recent clinical studies undertaken in a
      variety of outpatient settings, including colonoscopy, prostate biopsy, dental
      procedures, bone marrow biopsy, and the management of burns dressings, indicate
      that inhaled methoxyflurane has significant analgesic activity, without producing
      deep sedation or respiratory depression. Return to full psychomotor activity is
      rapid. Thus, methoxyflurane may be a suitable and well-tolerated alternative to
      traditional i.v. sedative agents for outpatient medical and surgical procedures.
      There are direct advantages to the patient in terms of rapid recovery and an
      early return to normal activities, and significant benefits for outpatient
      departments in terms of cost saving and rate of throughput. Further randomised
      controlled trials comparing the efficacy, safety, and cost-effectiveness of
      inhaled methoxyflurane against traditional i.v. sedative techniques are currently
      in progress.

PMID- 29661382
TI  - Comparison of target-controlled infusion and manual infusion for propofol
      anaesthesia in children.
AB  - BACKGROUND: One major criticism of prolonged propofol-based total i.v.
      anaesthesia (TIVA) in children is the prolonged recovery time. As target
      controlled infusion (TCI) obviates the need to manually calculate the infusion
      rate, the use of TCI may better match clinical requirements, reduce propofol
      dose, and shorten recovery time. METHODS: Children of ASA grade 1, aged 1-12 yr,
      were recruited and randomly assigned to TCI or manual infusion. Children in the
      TCI group had propofol delivered by TCI. Children for manual infusion had a
      loading dose of 2.5 mg kg-1 with subsequent infusion rates of 15, 13, 11, 10, and
      9 mg kg-1 h-1. Attending anaesthesiologists adjusted the propofol dosage to keep
      the Bispectral IndexTM (BIS) between 40 and 60. RESULTS: Seventy-four children
      completed the study. The time taken to extubate the trachea after cessation of
      propofol was 15.1 (5.5) and 16.2 (6.1) min for children who had TCI and manual
      infusion, respectively (P=0.42). The mean propofol infusion rate was 16.7
      [standard deviation (sd) 4.2] mg kg-1 h-1 in the TCI group and 14.6 (3.1) mg kg-1
      h-1 in the manual infusion group (P=0.036). The percentage of time when BIS was
      >60 was significantly lower in the TCI than the manual infusion group [10.2%
      (18.4%) vs 23.2% (26.3%), P=0.016]. DISCUSSION: Use of TCI led to higher propofol
      doses but not prolonged recovery time in children compared with manual infusion.
      It was associated with a greater percentage of time when the BIS was in the
      desired range and it may be an easier method for titration of propofol
      administration during anaesthesia or sedation. CLINICAL TRIAL REGISTRATION:
      ChiCTR-IOD-16010147.

PMID- 29661383
TI  - Does intranasal dexmedetomidine provide adequate plasma concentrations for
      sedation in children: a pharmacokinetic study.
AB  - BACKGROUND: Atomised intranasal dexmedetomidine administration is an attractive
      option when sedation is required for paediatric diagnostic procedures, as
      vascular access is not required. The risk of haemodynamic instability caused by
      dexmedetomidine necessitates better understanding of its pharmacokinetics in
      young children. To date, intranasal dexmedetomidine pharmacokinetics has only
      been studied in adults. METHODS: Eighteen paediatric patients received
      dexmedetomidine 1 or 2 MUg kg-1 intranasally or 1 MUg kg-1 i.v. Plasma
      concentrations were determined by liquid chromatography/mass spectrometry. Non
      compartmental analysis provided estimates of Cmax and Tmax. Volume of
      distribution, clearance, and bioavailability were estimated by simultaneous
      population PK analysis of data after intranasal and i.v. administration.
      Dexmedetomidine plasma concentration-time profiles were evaluated by simulation
      for intranasal and i.v. administration. RESULTS: An average peak plasma
      concentration of 199 pg ml-1 was achieved 46 min after 1 MUg kg-1 dosing and 355
      pg ml-1 was achieved 47 min after 2 MUg kg-1 dosing. A two-compartment
      pharmacokinetic model, with allometrically scaled parameters, adequately
      described the data. Typical bioavailability was 83.8% (95% confidence interval
      69.5-98.1%). CONCLUSION: Mean arterial plasma concentrations of dexmedetomidine
      in infants and toddlers approached 100 pg ml-1, the low end reported for sedative
      efficacy, within 20 min of an atomised intranasal administration of 1 MUg kg-1.
      Doubling the dose to 2 MUg kg-1 reached this plasma concentration within 10 min
      and achieved almost twice the peak concentration. Peak plasma concentrations with
      both doses were reached within 47 min of intranasal administration, with an
      overall bioavailability of 84%.

PMID- 29661385
TI  - Different methods of modelling intraoperative hypotension and their association
      with postoperative complications in patients undergoing non-cardiac surgery.
AB  - BACKGROUND: Associations between intraoperative hypotension (IOH) and
      postoperative complications have been reported. We examined whether using
      different methods to model IOH affected the association with postoperative
      myocardial injury (POMI) and acute kidney injury (AKI). METHODS: This two-centre
      cohort study included 10 432 patients aged >=50 yr undergoing non-cardiac
      surgery. Twelve different methods to statistically model IOH [representing
      presence, depth, duration, and area under the threshold (AUT)] were applied to
      examine the association with POMI and AKI using logistic regression analysis. To
      define IOH, eight predefined thresholds were chosen. RESULTS: The incidences of
      POMI and AKI were 14.9% and 14.8%, respectively. Different methods to model IOH
      yielded effect estimates differing in size and statistical significance. Methods
      with the highest odds were absolute maximum decrease in blood pressure (BP) and
      mean episode AUT, odds ratio (OR) 1.43 [99% confidence interval (CI): 1.15-1.77]
      and OR 1.69 (99% CI: 0.99-2.88), respectively, for the absolute mean arterial
      pressure 50 mm Hg threshold. After standardisation, the highest standardised ORs
      were obtained for depth-related methods, OR 1.12 (99% CI: 1.05-1.20) for absolute
      and relative maximum decrease in BP. No single method always yielded the highest
      effect estimate in every setting. However, methods with the highest effect
      estimates remained consistent across different BP types, thresholds, outcomes,
      and centres. CONCLUSIONS: In studies on IOH, both the threshold to define
      hypotension and the method chosen to model IOH affects the association of IOH
      with outcome. This makes different studies on IOH less comparable and hampers
      clinical application of reported results.

PMID- 29661386
TI  - Association between intraoperative opioid administration and 30-day readmission:
      a pre-specified analysis of registry data from a healthcare network in New
      England.
AB  - BACKGROUND: The use of intraoperative opioids may influence the rate of
      postoperative complications. This study evaluated the association between
      intraoperative opioid dose and the risk of 30-day hospital readmission. METHODS:
      We conducted a pre-specified analysis of existing registry data for 153 902
      surgical cases performed under general anaesthesia at Massachusetts General
      Hospital and two affiliated medical centres. We examined the association between
      total intraoperative opioid dose (categorised in quintiles) and 30-day hospital
      readmission, controlling for several patient-, anaesthetist-, and case-specific
      factors. RESULTS: Compared with low intraoperative opioid dosing [quintile 1,
      median (inter-quartile range): 8 (4-9) mg morphine equivalents], exposure to high
      dose opioids during surgery [quintile 5: 32 (27-41) equivalents] is an
      independent predictor of 30-day readmission [odds ratio (OR) 1.15 (95% confidence
      interval 1.07-1.24); P<0.001]. Ambulatory surgery patients receiving high opioid
      doses were found to have the greatest adjusted risk of readmission (OR 1.75;
      P<0.001) with a clear dose-response effect across quintiles (P for trend <0.05),
      and were more likely to be readmitted early (postoperative days 0-2 vs 3-30;
      P<0.001). Opioid class modified the association between total opioid dose and
      readmission, with longer-acting opioids demonstrating a stronger influence
      (P<0.001). We observed significant practice variability across individual
      anaesthetists in the utilisation of opioids that could not be explained by
      patient- and case-specific factors. CONCLUSIONS: High intraoperative opioid dose
      is a modifiable anaesthetic factor that varies in the practice of individual
      anaesthetists and affects postoperative outcomes. Conservative standards for
      intraoperative opioid dosing may reduce the risk of postoperative readmission,
      particularly in ambulatory surgery.

PMID- 29661384
TI  - A systematic review and consensus definitions for standardised end-points in
      perioperative medicine: pulmonary complications.
AB  - BACKGROUND: There is a need for robust, clearly defined, patient-relevant outcome
      measures for use in randomised trials in perioperative medicine. Our objective
      was to establish standard outcome measures for postoperative pulmonary
      complications research. METHODS: A systematic literature search was conducted
      using MEDLINE, Web of Science, SciELO, and the Korean Journal Database.
      Definitions were extracted from included manuscripts. We then conducted a three
      stage Delphi consensus process to select the optimal outcome measures in terms of
      methodological quality and overall suitability for perioperative trials. RESULTS:
      From 2358 records, the full texts of 81 manuscripts were retrieved, of which 45
      met the inclusion criteria. We identified three main categories of outcome
      measure specific to perioperative pulmonary outcomes: (i) composite outcome
      measures of multiple pulmonary outcomes (27 definitions); (ii) pneumonia (12
      definitions); and (iii) respiratory failure (six definitions). These were rated
      by the group according to suitability for routine use. The majority of
      definitions were given a low score, and many were imprecise, difficult to apply
      consistently, or both, in large patient populations. A small number of highly
      rated definitions were identified as appropriate for widespread use. The group
      then recommended four outcome measures for future use, including one new
      definition. CONCLUSIONS: A large number of postoperative pulmonary outcome
      measures have been used, but most are poorly defined. Our four recommended
      outcome measures include a new definition of postoperative pulmonary
      complications, incorporating an assessment of severity. These definitions will
      meet the needs of most clinical effectiveness trials of treatments to improve
      postoperative pulmonary outcomes.

PMID- 29661387
TI  - Pre-hospital advanced airway management by anaesthetist and nurse anaesthetist
      critical care teams: a prospective observational study of 2028 pre-hospital
      tracheal intubations.
AB  - BACKGROUND: Pre-hospital tracheal intubation success and complication rates vary
      considerably among provider categories. The purpose of this study was to estimate
      the success and complication rates of pre-hospital tracheal intubation performed
      by physician anaesthetist or nurse anaesthetist pre-hospital critical care teams.
      METHODS: Data were prospectively collected from critical care teams staffed with
      a physician anaesthetist or a nurse anaesthetist according to the Utstein
      template for pre-hospital advanced airway management. The patients served by six
      ambulance helicopters and six rapid response vehicles in Denmark, Finland,
      Norway, and Sweden from May 2015 to November 2016 were included. RESULTS: The
      critical care teams attended to 32 007 patients; 2028 (6.3%) required pre
      hospital tracheal intubation. The overall success rate of pre-hospital tracheal
      intubation was 98.7% with a median intubation time of 25 s and an on-scene time
      of 25 min. The majority (67.0%) of the patients' tracheas were intubated by
      providers who had performed >2500 tracheal intubations. The success rate of
      tracheal intubation on the first attempt was 84.5%, and 95.9% of intubations were
      completed after two attempts. Complications related to pre-hospital tracheal
      intubation were recorded in 10.9% of the patients. Intubations after rapid
      sequence induction had a higher success rate compared with intubations without
      rapid sequence induction (99.4% vs 98.1%; P=0.02). Physicians had a higher
      tracheal intubation success rate than nurses (99.0% vs 97.6%; P=0.03).
      CONCLUSIONS: When performed by experienced physician anaesthetists and nurse
      anaesthetists, pre-hospital tracheal intubation was completed rapidly with high
      success rates and a low incidence of complications. CLINICAL TRIAL NUMBER: NCT
      02450071.

PMID- 29661388
TI  - Degree of obesity is not associated with more than one intubation attempt: a
      large centre experience.
AB  - BACKGROUND: The role of obesity as a risk factor for difficult intubation remains
      controversial. We primarily assessed the association between body mass index
      (BMI) and difficult tracheal intubation. METHODS: We analysed electronic records
      of more than 67 000 adults having elective non-cardiac surgery requiring tracheal
      intubation at the Cleveland Clinic between 2011 and 2015. The association between
      BMI and difficult intubation, defined as more than one intubation attempt, was
      assessed using multivariable logistic regression adjusting for pre-specified
      confounders. RESULTS: Amongst 40 183 patients with BMI <30 kg m-2 and 27 519 with
      BMI >=30 kg m-2, 9% required more than one intubation attempt. Increasing BMI up
      to 30 kg m-2 was significantly associated with increased odds of more than one
      intubation attempt [odds ratio (OR): 1.03; 97.5% confidence interval (CI): 1.02,
      1.04] per unit increase in BMI, P < 0.001. However, the odds of difficult
      intubation remained unchanged once BMI exceeded 30 kg m-2 (P = 0.08). The results
      were similar when analysis was restricted to patients without history of airway
      abnormalities in whom intubation was attempted using a standard direct
      laryngoscope (OR: 1.03; 99.4% CI: 1.01, 1.04) per kg m-2 increase in BMI <30 kg m
      2). CONCLUSIONS: Increasing BMI was associated with increasing odds of difficult
      intubation in the lean range. At higher BMI, the odds of difficult intubation
      remain elevated, but there is no additional increase in odds with further
      increase in BMI. Obese patients were thus harder to intubate than lean ones, but
      difficult intubation was no more likely in morbidly obese patients than in those
      who were only slightly obese.

PMID- 29661389
TI  - Esketamine counters opioid-induced respiratory depression.
AB  - BACKGROUND: Opioids can produce life-threatening respiratory depression. This
      study tested whether subanaesthetic doses of esketamine stimulate breathing in an
      established human model of opioid-induced respiratory depression. METHODS: In a
      study with a randomised, double blind, placebo controlled, crossover design, 12
      healthy, young volunteers of either sex received a dose escalating infusion of
      esketamine (cumulative dose 40 mg infused in 1 h) on top of remifentanil-induced
      respiratory depression. A population pharmacokinetic-pharmacodynamic analysis was
      performed with sites of drug action at baseline ventilation, ventilatory CO2
      chemosensitivity, or both. RESULTS: Remifentanil reduced isohypercapnic
      ventilation (end-tidal PCO2 6.5 kPa) by approximately 40% (from 20 to 12 litre
      min-1) in esketamine and placebo arms of the study, through an effect on baseline
      ventilation and ventilatory CO2 sensitivity. The reduction in ventilation was
      related to a remifentanil effect on ventilatory CO2 sensitivity (~39%) and on
      baseline ventilation (~61%). Esketamine increased breathing through an exclusive
      stimulatory effect on ventilatory CO2 sensitivity. The remifentanil concentration
      that reduced ventilatory CO2 sensitivity by 50% (C50) was doubled at an
      esketamine concentration of 127 (84-191) ng ml-1 [median (interquartile range)];
      the esketamine effect was rapid and driven by plasma pharmacokinetics. Placebo
      had no systematic effect on opioid-induced respiratory depression. CONCLUSIONS:
      Esketamine effectively countered remifentanil-induced respiratory depression, an
      effect that was attributed to an increase in remifentanil-reduced ventilatory CO2
      chemosensitivity.

PMID- 29661390
TI  - Reporting of sex and gender in human studies published in anaesthesia journals.

PMID- 29661391
TI  - Sex is not gender and why it matters for population health.

PMID- 29661392
TI  - Defining modes of anaesthesia: response to 'Perioperative outcomes in the context
      of mode of anaesthesia for patients undergoing hip fracture surgery: systematic
      review and meta-analysis'.

PMID- 29661393
TI  - Hip fracture anaesthesia: the importance of inputs.

PMID- 29661394
TI  - On differences between systematic reviews.

PMID- 29661395
TI  - Evidence-based medicine: time to upend the pyramid for some clinical situations?

PMID- 29661396
TI  - The World Health Organisation surgical safety checklist does not reduce mortality
      in general surgery.

PMID- 29661397
TI  - Surgical cricothyrotomy: the tracheal-tube dilemma.

PMID- 29661398
TI  - Response to 'Surgical cricothyroidotomy-the tracheal tube dilemma'.

PMID- 29661399
TI  - Uvula necrosis after fibreoptic intubation.

PMID- 29661400
TI  - Corrigendum to "Perineural dexamethasone - the dilemma of systematic reviews and
      meta-analyses" [Br J Anaesth 2018; 120: 201-203].

PMID- 29661401
TI  - Erratum to 'Management of antiplatelet therapy in patients with coronary stents
      undergoing noncardiac surgery: association with adverse events' [Br J Anaesth
      2018; 120: 67-76].

PMID- 29661402
TI  - Increasing the utility of target-controlled infusions: one model to rule them
      all.

PMID- 29661403
TI  - Can nitric oxide tame the ketamine tiger?

PMID- 29661404
TI  - Bioblasts, anaesthesia, and power failure: rein in the excitement.

PMID- 29661405
TI  - Front of neck: continued discovery of this anatomy essential for airway
      management.

PMID- 29661406
TI  - Pre-hospital anaesthesia: no longer the 'poor relative' of high quality in
      hospital emergency airway management.

PMID- 29661407
TI  - Big data for big patients: gaining insight into risks for tracheal intubation in
      obese patients.

PMID- 29661408
TI  - Cerebrospinal-fluid drain-related complications in patients undergoing open and
      endovascular repairs of thoracic and thoraco-abdominal aortic pathologies: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Cerebrospinal-fluid (CSF) drainage is recommended by current
      guidelines for spinal protection during open and endovascular repairs of thoracic
      and thoraco-abdominal aortic aneurysms. In the published literature, great
      variability exists in the rate of CSF-related complications and morbidity.
      Herein, we perform a systematic review and meta-analysis on the incidence of CSF
      drainage-related complications, and compare the complication rates between open
      and endovascular repairs. METHODS: The systematic review was conducted according
      to the Meta-Analysis of Observational Studies in Epidemiology guidelines. Thirty
      four studies (4714 patients) were included in the quantitative analysis. The CSF
      drainage-related complications were categorised as mild, moderate, and severe.
      Pooled event rates for each complication category were estimated using a random
      effect model. Random-effect uni- and multivariable meta-regression analyses were
      used to assess the effect of aortic-repair approach (open vs endovascular) and
      the CSF drainage criteria on CSF drainage-related complications. RESULTS: The
      pooled event rates were 6.5% [95% confidence interval (CI): 4.3-9.8%] for overall
      complications, 2% (95% CI: 1.1-3.4%) for minor complications, 3.7% (95% CI: 2.5
      5.6%) for moderate complications, and 2.5% (95% CI: 1.6-3.8%) for severe
      complications. The drainage-related-mortality pooled event rate was 0.9% (95% CI:
      0.6-1.4%). The uni- and multivariable meta-regression analyses showed no
      difference in complication rates between the open and endovascular approaches, or
      between the different CSF drainage protocols. CONCLUSION: The complication rate
      for CSF drainage is not negligible. Our results help define a more accurate risk
      benefit ratio for CSF drain placement at the time of repair of thoracic and
      thoraco-abdominal aneurysms.

PMID- 29661409
TI  - Anticoagulant and side-effects of protamine in cardiac surgery: a narrative
      review.
AB  - Neutralisation of systemic anticoagulation with heparin in cardiac surgery with
      cardiopulmonary bypass requires protamine administration. If adequately dosed,
      protamine neutralises heparin and reduces the risk of postoperative bleeding.
      However, as its anticoagulant properties are particularly exerted in the absence
      of heparin, overdosing of protamine may contribute to bleeding and increased
      transfusion requirements. This narrative review describes the mechanisms
      underlying the anticoagulant properties and side-effects of protamine, and the
      impact of protamine dosing on the activated clotting time and point-of-care
      viscoelastic test results, and explains the distinct protamine dosing strategies
      in relation to haemostatic activation and postoperative bleeding. The available
      evidence suggests that protamine dosing should not exceed a protamine-to-heparin
      ratio of 1:1. In particular, protamine-to-heparin dosing ratios >1 are associated
      with more postoperative 12 h blood loss. The optimal protamine-to-heparin ratio
      in cardiac surgery has, however, not yet been elaborated, and may vary between
      0.6 and 1.0 based on the initial heparin dose.

PMID- 29661410
TI  - Use of prothrombin complex concentrate for management of coagulopathy after
      cardiac surgery: a propensity score matched comparison to plasma.
AB  - BACKGROUND: An important cause of coagulopathy in cardiac surgery is impaired
      thrombin generation. While plasma is often used to correct this element of the
      coagulopathy, studies in vitro suggest that prothrombin complex concentrates
      (PCCs) might be more effective. Comparative data, however, are scant. METHODS: We
      compared the outcomes of those who received only plasma with those who received
      PCCs (with or without plasma) for management of coagulopathy in patients who
      underwent cardiac surgery with cardiopulmonary bypass at a single institution
      from 2012 to 2016. Propensity score matching was used to obtain between-group
      balance. Primary outcome was avoidance of perioperative red cell transfusions.
      Other outcomes were incidence of massive transfusion (more than nine red cell
      units), refractory bleeding (requiring factor VIIa), and adverse events. RESULTS:
      Of 6362 patients, 1151 (18.2%) received plasma without any PCCs, and 204 (3.2%)
      received PCCs, either with (n=125) or without plasma (n=79). Overall, patient
      risk-profile was higher in the PCCs group. In a well-balanced propensity score
      match that included 117 patients per group, the odds ratio (OR) for red cell
      avoidance was 2.4-fold [95% confidence interval (CI) 1.2-4.8] higher in the PCCs
      group. Massive transfusion (OR 0.58; 95% CI 0.33-1.0) and refractory bleeding (OR
      0.49; 95% CI 0.24-1.03) incidences were almost significantly lower in the PCCs
      group. The adverse event profiles were similar. CONCLUSIONS: Our exploratory
      study suggests that the use of PCCs as part of a multifaceted coagulation
      management strategy may have blood-sparing effects. Their incorporation into
      clinical practice, however, must await determination of their risk-benefit
      profile via multicentre randomised trials.

PMID- 29661411
TI  - The fragility of statistically significant findings in randomised controlled
      anaesthesiology trials: systematic review of the medical literature.
AB  - The fragility index (FI), the number of events the statistical significance a
      result depends on, and the number of patients lost to follow-up are important
      parameters for interpreting randomised clinical trial results. We evaluated these
      two parameters in randomised controlled trials in anaesthesiology. For this, we
      performed a systematic search of the medical literature, seeking articles
      reporting on anaesthesiology trials with a statistically significant difference
      in the primary outcome and published in the top five general medicine journals,
      or the top 15 anaesthesiology journals. We restricted the analysis to trials
      reporting clinically important primary outcome measures. The search identified
      139 articles, 35 published in general medicine journals and 104 in
      anaesthesiology journals. The median (inter-quartile range) sample size was 150
      (70-300) patients. The FI was 4 (2-17) and 3 (2-7), and the number of patients
      lost to follow-up was 0 (0-18) and 0 (0-6) patients in trials published in
      general medicine and anaesthesiology journals, respectively. The number of
      patients lost to follow-up exceeded the FI in 41 and 27% in trials in general
      medicine journals and anaesthesiology journals, respectively. The FI positively
      correlated with sample size and number of primary outcome events, and negatively
      correlated with the reported P-values. The results of this systematic review
      suggest that statistically significant differences in randomised controlled
      anaesthesiology trials are regularly fragile, implying that the primary outcome
      status of patients lost to follow-up could possibly have changed the reported
      effect.

PMID- 29661412
TI  - Pharmacokinetic-pharmacodynamic model for propofol for broad application in
      anaesthesia and sedation.
AB  - BACKGROUND: Pharmacokinetic (PK) and pharmacodynamic (PD) models are used in
      target-controlled-infusion (TCI) systems to determine the optimal drug
      administration to achieve a desired target concentration in a central or effect
      site compartment. Our aim was to develop a PK-PD model for propofol that can
      predict the bispectral index (BIS) for a broad population, suitable for TCI
      applications. METHODS: Propofol PK data were obtained from 30 previously
      published studies, five of which also contained BIS observations. A PK-PD model
      was developed using NONMEM. Weight, age, post-menstrual age (PMA), height, sex,
      BMI, and presence/absence of concomitant anaesthetic drugs were explored as
      covariates. The predictive performance was measured across young children,
      children, adults, elderly, and high-BMI individuals, and in simulated TCI
      applications. RESULTS: Overall, 15 433 propofol concentration and 28 639 BIS
      observations from 1033 individuals (672 males and 361 females) were analysed. The
      age range was from 27 weeks PMA to 88 yr, and the weight range was 0.68-160 kg.
      The final model uses age, PMA, weight, height, sex, and presence/absence of
      concomitant anaesthetic drugs as covariates. A 35-yr-old, 170 cm, 70 kg male
      (without concomitant anaesthetic drugs) has a V1, V2, V3, CL, Q2, Q3, and ke0 of
      6.28, 25.5, 273 litres, 1.79, 1.75, 1.11 litres min-1, and 0.146 min-1,
      respectively. The propofol TCI administration using the model matches well with
      recommendations for all age groups considered for both anaesthesia and sedation.
      CONCLUSIONS: We developed a PK-PD model to predict the propofol concentrations
      and BIS for broad, diverse population. This should be useful for TCI in
      anaesthesia and sedation.

PMID- 29661413
TI  - Pharmacokinetic and pharmacodynamic study of intranasal and intravenous
      dexmedetomidine.
AB  - BACKGROUND: Intranasal dexmedetomidine produces safe, effective sedation in
      children and adults. It may be administered by drops from a syringe or by nasal
      mucosal atomisation (MAD NasalTM). METHODS: This prospective, three-period,
      crossover, double-blind study compared the pharmacokinetic (PK) and
      pharmacodynamic (PD) profile of i.v. administration with these two different
      modes of administration. In each session each subject received 1 MUg kg-1
      dexmedetomidine, either i.v., intranasal with the atomiser or intranasal by
      drops. Dexmedetomidine plasma concentration and Ramsay sedation score were used
      for PK/PD modelling by NONMEM. RESULTS: The i.v. route had a significantly faster
      onset (15 min, 95% CI 15-20 min) compared to intranasal routes by atomiser (47.5
      min, 95% CI 25-135 min), and by drops (60 min, 95%CI 30-75 min), (P<0.001). There
      was no significant difference in sedation duration across the three treatment
      groups (P=0.88) nor in the median onset time between the two modes of intranasal
      administration (P=0.94). A 2-compartment disposition model, with transit
      intranasal absorption and clearance driven by cardiac output using the well
      stirred liver model, was the final PK model. Intranasal bioavailability was
      estimated to be 40.6% (95% CI 34.7-54.4%) and 40.7% (95% CI 36.5-53.2%) for
      atomisation and drops respectively. Sedation score was modelled via a sigmoidal
      Emax model driven by an effect compartment. The effect compartment had an
      equilibration half time 3.3 (95% CI 1.8-4.7) min-1, and the EC50 was estimated to
      be 903 (95% CI 450-2344) pg ml-1. CONCLUSIONS: There is no difference in
      bioavailability with atomisation or nasal drops. A similar degree of sedation can
      be achieved by either method. CLINICAL TRIAL REGISTRATION: HKUCTR-1617.

PMID- 29661415
TI  - Reversal of dabigatran by intraosseous or intravenous idarucizumab in a porcine
      polytrauma model.
AB  - BACKGROUND: Idarucizumab is licensed to reverse dabigatran in life-threatening
      haemorrhage. Establishment of venous access can be challenging, and the
      intraosseous (IO) route is a potentially life-saving alternative. In this study,
      we compared the efficacy and safety of IO or intravenous (i.v.) idarucizumab for
      dabigatran reversal in a porcine polytrauma model. METHODS: Male pigs (n=21)
      received oral dabigatran etexilate (30 mg kg-1 bid) for 3 days. On the 4th day,
      animals received dabigatran infusion and were randomised 1:1:1 to receive IO
      saline (control), i.v. idarucizumab (60 mg kg-1), or IO idarucizumab (60 mg kg
      1), or animals were included in a sham group (n=7). Study treatment was
      administered after polytrauma and the animals were monitored for 240 min, or
      until death. Coagulation status was monitored by thromboelastometry,
      thromboelastography, and thrombin measurements. RESULTS: Total blood loss was
      lowest in sham animals [521 (52) ml, P<0.01 vs all other groups], and comparable
      in the two idarucizumab groups [IO: 1085 (102) ml vs i.v.: 1142 (125) ml], and
      highest in the control group [4065 (557) ml, P<0.001 vs all other groups].
      Survival to 240 min was 100% in the sham group and both idarucizumab groups, and
      14% in the control group. IO and i.v. idarucizumab promptly normalised global
      coagulation assays and thrombin generation. Thromboelastography showed a strong
      correlation between dabigatran concentrations and R-time (R2=0.90 and 0.89) in
      idarucizumab-treated animals. CONCLUSIONS: Intravenous and intraosseous
      idarucizumab were comparable for reversing dabigatran in a porcine trauma model.
      Dabigatran reversal could be monitored using fully automated thromboelastography.

PMID- 29661414
TI  - Dexmedetomidine metabolic clearance is not affected by fat mass in obese
      patients.
AB  - BACKGROUND: Obesity has been associated with reduced dexmedetomidine clearance,
      suggesting impaired hepatic function or reduced hepatic blood flow. The aim of
      this study was to clarify the effect of obesity in dexmedetomidine metabolic
      clearance. METHODS: Forty patients, ASA I-III, 18-60 yr old, weighing 47-126 kg,
      scheduled for abdominal laparoscopic surgery, were enrolled. Anaesthetic agents
      (propofol, remifentanil, and dexmedetomidine) were dosed based on lean body
      weight measured by dual X-ray absorptiometry. Serial venous samples were drawn
      during and after dexmedetomidine infusion. A pharmacokinetic analysis was
      undertaken using non-linear mixed-effect models. In the modelling approach, the
      total body weight, lean body weight, and adjusted body weight were first tested
      as size descriptors for volumes and clearances. Hepatic blood flow, liver
      histopathology, liver enzymes, and gene expression of metabolic enzymes (UGT2B10
      and UGT1A4) were tested as covariates of dexmedetomidine metabolic clearance. A
      decrease in NONMEM objective function value (DeltaOFV) of 3.84 points, for an
      added parameter, was considered significant at the 0.05 level. RESULTS: A total
      of 637 dexmedetomidine serum samples were obtained. A two-compartmental model
      scaled to measured lean weight adequately described the dexmedetomidine
      pharmacokinetics. Liver blood flow was a covariate for dexmedetomidine clearance
      (DeltaOFV=-5.878). Other factors, including fat mass, histopathological damage,
      and differential expression of enzymes, did not affect the dexmedetomidine
      clearance in the population studied (DeltaOFV<3.84). CONCLUSIONS: We did not find
      a negative influence of obesity in dexmedetomidine clearance when doses were
      adjusted to lean body weight. Liver blood flow showed a significant effect on
      dexmedetomidine clearance. CLINICAL TRIAL REGISTRATION: NCT02557867.

PMID- 29661416
TI  - Anaemia and red blood cell transfusion in intracranial neurosurgery: a
      comprehensive review.
AB  - Both anaemia and blood transfusion are associated with poor outcomes in the
      neurosurgical population. Based on the available literature, the optimal
      haemoglobin concentration for neurologically injured patients appears to be in
      the range of 9.0-10.0 g dl-1, although the individual risks and benefits should
      be weighed. Several perioperative blood conservation strategies have been used
      successfully in neurosurgery, including correction of anaemia and coagulopathy,
      use of antifibrinolytics, and intraoperative cell salvage. Avoidance of non
      steroidal anti-inflammatory drugs and starch-containing solutions is recommended
      given the potential for platelet dysfunction.

PMID- 29661417
TI  - Postoperative delirium in total knee and hip arthroplasty patients: a study of
      perioperative modifiable risk factors.
AB  - BACKGROUND: Postoperative delirium continues to pose major clinical difficulties.
      While unmodifiable factors (e.g. age and comorbidity burden) are commonly studied
      risk factors for delirium, the role of modifiable factors, such as anaesthesia
      type and commonly used perioperative medications, remains understudied. This
      study aims to evaluate the role of modifiable factors for delirium after hip and
      knee arthroplasties. METHODS: We performed a retrospective study of 41 766
      patients who underwent hip or knee arthroplasties between 2005 and 2014 at a
      single institution. Data were collected as part of routine patient care.
      Multivariable logistic regression models assessed associations between
      anaesthesia type and commonly used perioperative medications (opioids,
      benzodiazepines, and ketamine) and postoperative delirium. Odds ratios (OR) and
      95% confidence intervals (CI) are reported. Various sensitivity analyses are also
      considered, including multiple imputation methods to address missing data.
      RESULTS: Postoperative delirium occurred in 2.21% (n=922) of all patients. While
      patients who received neuraxial anaesthesia were at lower risk for postoperative
      delirium (compared with general anaesthesia; epidural OR 0.59 CI 0.38-0.93;
      spinal OR 0.55 CI 0.37-0.83; combined spinal/epidural OR 0.56 CI 0.40-0.80),
      those given intraoperative ketamine (OR 1.27 CI 1.01-1.59), opioids (OR 1.25 CI
      1.09-1.44), postoperative benzodiazepines (OR 2.47 CI 2.04-2.97), and ketamine
      infusion (OR 10.59 CI 5.26-19.91) were at a higher risk. CONCLUSIONS: In this
      cohort of hip and knee arthroplasty patients, anaesthesia type and perioperative
      medications were associated with increased odds for postoperative delirium. Our
      results support the notion that modifiable risk factors may exacerbate or
      attenuate risk for postoperative delirium.

PMID- 29661418
TI  - 15th Brazilian Transplant Congress.

PMID- 29661419
TI  - Challenges of Organ Donation: Potential Donors for Transplantation in an Area of
      Brazil's Northeast.
AB  - BACKGROUND: New strategies to manage the pool of potential donors are needed to
      increase organ donation rates. The purpose of the study was to identify the main
      causes of lack of organ donation and to identify the sociodemographic and
      clinical profiles of potential organ donors in an area of northeastern Brazil.
      METHODS: We conducted a cross-sectional, retrospective, observational study
      between November 2015 and January 2017. RESULTS: A total of 150 potential donors
      were included in the sample. The main cause of death among potential donors was
      hemorrhagic stroke (35.3%). Hypertension was the most prevalent comorbidity
      (25.6%). Family member's refusal was cited as the most common reason for not
      performing organ donation (49.4%). Among the causes of family member's refusal,
      the most prevalent was declaration of non-consent in life (23%), followed by
      family disagreement (20.3%). CONCLUSION: There is clearly a need for public
      educational efforts with regard to organ donation. Educational advertising
      campaigns can help improve the authorization rate of organ donation.

PMID- 29661420
TI  - Use of Georges Lopez Institute Preservation Solution IGL-1 in Pancreas
      Transplantation: A Series of 47 Cases.
AB  - BACKGROUND: Graft preservation continues to be one of the main pillars of
      pancreas transplantation (PT). Surgical complications, possibly caused or
      facilitated by organ damage during preservation, continue to occur more
      frequently after PT than for any other abdominal organ. During the past few
      years, the Georges Lopez Institute preservation solution IGL-1 has been
      introduced with satisfactory results for the perfusion and cold storage of
      abdominal grafts such as kidney and liver. METHODS: Aspects related to 47 PTs
      with the use of IGL-1 as the only preservation solution performed from January
      2012 to September 2017 at Hospital Santa Isabel, Blumenau, Brazil, were
      retrospectively analyzed. RESULTS: Considering the 46 transplanted patients (1
      patient underwent 2 PTs), graft loss followed by death occurred in 2 patients: 1
      due to pancreatic thrombosis, and 1 due to sepsis. In addition, a 3rd patient
      died with a functioning graft due to sepsis of an infected hematoma. In 1
      patient, graft loss occurred due to pancreatic thrombosis and was later
      retransplanted. One patient presented post-transplantation pancreatitis. The
      overall survival of patients in 1 month after transplantation was 95.7%, and
      graft survival in the 1st month was 93.6%. CONCLUSIONS: In all patients
      transplanted with the use of IGL-1, normalization of pancreatic function occurred
      early after reperfusion, there was no delayed graft function, and all
      transplanted patients maintained a non-insulin-dependent status after
      transplantation. The use of IGL-1 as preservation solution for PT is safe and
      effective.

PMID- 29661421
TI  - Liver Transplantation Using Prolonged Cold Ischemia Time Grafts Preserved With
      Institute George-Lopez-1 Solution.
AB  - Institute George-Lopez-1 (IGL-1) solution is a preservation solution with lower
      potassium and lower viscosity than the University of Wisconsin solution that has
      been recently used in liver transplantation. In the present series, we compare
      the outcome of liver grafts from brain-dead donors preserved in IGL-1cold storage
      solution, with cold ischemia times (CITs) longer than 8 hours and those less than
      8 hours. Two hundred fifty-two liver transplantations performed from January 2014
      to December 2016 at Hospital Santa Isabel, Blumenau, Brazil, were retrospectively
      analyzed. The patients were divided in two groups according to the CIT. Group I
      patients (N = 155) had less than 8 hours of CIT with a mean age of 54 +/- 11.35
      years, whereas group II patients (N = 97) had more than 8 hours of CIT with a
      mean age of 52 +/- 12.5 years. There was no difference between the groups related
      to indication for liver transplantation and donor characteristics. The only
      difference statically significant on laboratory data was between the levels of
      aspartate aminotransferase at day 1 after transplantation. On day 7 post
      transplantation there was no difference statistically significant between
      aspartate aminotransferase, alanine aminotransferase, and bilirubin levels
      between the two groups. Similar 1-year patient survival rates were found in both
      groups, with 85.88% for group I and 85.75% in group II. The IGL-1 solution has
      been shown to be safe, effective, and with good results in liver
      transplantations. Early graft function and 1-year patient survival rates did not
      differ when grafts preserved for less than 8 hours were compared to those with
      CIT greater than 8 hours.

PMID- 29661422
TI  - Graft Protection Against Cold Ischemia Preservation: An Institute George Lopez 1
      and Histidine-tryptophan-ketoglutarate Solution Appraisal.
AB  - Cold storage of organs in preservation solutions, such as Institute George Lopez
      1 (IGL-1) or histidine-tryptophan-ketoglutarate (HTK), is a mandatory step for
      organ transplantation. This preservation leads to an ischemic injury that affects
      the outcome of the organ. This article studies the liver graft eluate after organ
      recovery using IGL-1 or HTK solutions. We explore the influence of the volume
      used for washing out the liver and the consequences in the graft preservation
      when both solutions are used. Livers were washed out with different volumes of
      HTK and IGL-1 according to manufacturers' instructions and then preserved in both
      solutions for 24 hours at 4 degrees C. Tissue and eluates were collected for
      subsequent analyses. We measured transaminases (aspartate aminotransferase and
      alanine aminotransferase), histology by hematoxylin/eosin staining, and red blood
      cell and hemoglobin counts, respectively. After washing out and cold storage, the
      IGL-1 processed livers showed better preservation than those with HTK solution;
      however, in this latter case, an important accumulation of erythrocytes was found
      when compared to IGL-1. These data were consistent with the higher hemoglobin and
      red blood cell counts observed for IGL-1 eluates after 24 hours. The volume used
      for washing out the organ depends on the composition and properties of the organ
      preservation solutions (ie, IGL-1 and HTK); this is an important factor for the
      graft cold preservation. The total volume used for washing out the graft should
      be considered because it has a direct impact on the total cost for clinical
      transplantations.

PMID- 29661423
TI  - Living-Donor Kidney Transplantation: Donor-Recipient Function Correlation.
AB  - BACKGROUND: With the rising prevalence of living-donor kidney transplantation,
      evaluation of factors correlated with renal function in the donor-recipient pair
      constitutes a main goal for kidney transplantation clinicians. Our objective was
      to analyze the more relevant donor characteristics that contribute to donor and
      recipient estimated glomerular filtration rates (eGFR) after 1 year. METHODS: We
      evaluated 48 consecutive donor-recipient pairs from our unit. RESULTS: Mean donor
      age was 46 +/- 11 years, with 71% being women. Mean recipient age was 35 +/- 12
      years, with 54% being men. Mean duration of donor hospitalization was 7 +/- 2
      days. Donor eGFR was 104 +/- 11 mL/min/1.73 m2 before donation and 70 +/- 14
      mL/min/1.73 m2 at discharge. After 1 year, donor eGFR was 71 +/- 12 mL/min/1.73
      m2 and recipient eGFR was 69 +/- 10 mL/min/1.73 m2. Donor eGFR <100 mL/min/1.73
      m2 before donation and age >50 years correlated with 17.7- and 8.9-fold increased
      risks, respectively, of recipient eGFR <60 mL/min/1.73 m2 after 1 year. Donor
      being female, although statistically associated with worse graft function,
      compared with a male donor (P = .020), did not represent a significantly
      increased risk of recipient eGFR <60 mL/min/1.73 m2. Higher donor body mass index
      (BMI) also associated with a lower kidney function for donors (P = .048). In
      multivariate linear regression to predict pairs' eGFRs after 1 year, only donor
      eGFR before donation and at discharge retained statistical significance (P <=
      .001 and P = .045, respectively). CONCLUSIONS: Excluding unpredictable
      complications in the post-transplantation period, donor eGFR before donation,
      eGFR at discharge, and age were the best parameters to predict recipient and
      donor eGFRs after 1 year and can be used as a tool for managing expectations
      regarding the post-transplantation period.

PMID- 29661424
TI  - Intravenous Immunoglobulin and Rituximab in HLA Highly Sensitized Kidney
      Transplant Recipients.
AB  - INTRODUCTION: HLA-sensitized patients are penalized both in the access to kidney
      transplantation (KT) and, once transplanted, in the incidence of rejections and
      long-term allograft survival despite aggressive induction and maintenance
      therapy. METHODS: This study retrospectively evaluates the impact of combining T-
      and B-cell-depleting agents and intravenous immunoglobulin for induction therapy
      in 45 highly sensitized KT patients (anti-panel reactive antibodies >60%,
      positive flow cytometry crossmatch or donor specific antibodies at the time of
      transplantation). The outcome data included the occurrence of biopsy-proven acute
      rejection, new-onset proteinuria, development of leukopenia, incidence of
      poliomavirus infection (BK or JC virus), fungal or bacterial infection after KT,
      de novo neoplasia, graft function, graft loss, or death with functioning KT.
      RESULTS: The average panel reactive antibody was 62.5%; 41 patients (91.1%) had
      >=3 HLA mismatches with the donor and 91.1% of patients had class I or II anti
      HLA antibodies. Fourteen patients (31.1%) presented pre-KT donor-specific
      antibodies and 6 patients (13.3%) had a positive flow cytometry cross-match at
      the time of transplantation. The incidence of acute rejection in the first 6
      months was 24.4% and the cumulative incidence was 37.8%. Two patients were
      diagnosed with leukopenia in the first 6 months after KT. Two patients (4.5%) had
      cytomegalovirus disease, 17 patients (37.8%) were diagnosed with bacterial
      infections. Cutaneous neoplasms were identified in 5 patients (11.1%) and solid
      tumors in 4 (8.9%). The death-censored graft survival was 100% in the first 6
      months and 93.5% at the last evaluation. Patient survival in the same periods was
      97.8% and 93.3%, respectively. CONCLUSIONS: Induction immunosuppressive therapy
      with intravenous immunoglobulin and rituximab is effective; outcomes demonstrate
      an excellent patient and allograft survival and allograft function over the
      follow-up period.

PMID- 29661425
TI  - Soluble CD30, Acute Rejection, and Graft Survival: Pre- and 6-Month Post
      Transplant Determinations-When Is the Best Time to Measure?
AB  - BACKGROUND: Pretransplantation soluble CD30 (sCD30) has been shown to be a good
      predictor of acute rejection (AR) and graft loss. This study aimed to evaluate
      the effectiveness of sCD30 measured pretransplant and up to 6 months after
      transplantation as a predictor of AR, graft loss, and survival at 5 years post
      transplantation. Subjects were patients receiving living donor renal transplants
      at Bonsucesso Federal Hospital (Rio de Janeiro) in 2006 and between August 2010
      and May 2011. METHODS: sCD30 was analyzed in samples collected pretransplantation
      and 7, 14, and 21, 28 days and 3, 4, 5, and 6 months post-transplantation from 73
      kidney recipients. RESULTS: Patients in the AR group did not present a positive
      correlation with the sCD30 levels pretransplant (P = .54); in the post-transplant
      period, the 7- to 14-day samples showed patients with AR had higher levels of
      this biomarker (P = .036). The graft survival in 5 years of follow-up was not
      different between groups. CONCLUSIONS: The best time to predict AR using sCD30 is
      the 7- to 14-day sample; however, identifying and following the decrease of this
      biomarker from pre- to post-transplant seems to be better than just 1
      measurement. The sCD30 post-transplant is another tool that may be used in
      monitoring patients after renal transplantation.

PMID- 29661426
TI  - Delayed Graft Function, Predictive Factors, and 7-Year Outcome of Deceased Donor
      Kidney Transplant Recipients With Different Immunologic Profiles.
AB  - BACKGROUND: Delayed graft function (DGF) is the major post-transplant cause of
      deleterious effects to the allograft and is associated with poor allograft
      survival. The aim of this study was to report the outcomes of 236 kidney
      transplant recipients with different immunologic profiles. METHODS: All patients
      underwent transplantation (2008-2016) with a deceased donor at the University
      Hospital of the Faculty of Medical Science, Belo Horizonte, Minas Gerais, Brazil.
      Patients were classified into 3 groups according to immunologic profiles:
      nonsensitized (NS), sensitized without donor-specific antibody (SDSA-), or
      sensitized with donor-specific antibody (SDSA+). RESULTS: DGF was observed in 128
      (54.24%), including 63 (49.22%) NS, 51 (39.84%) SDSA-, and 14 (10.94%) SDSA+
      patients. The development of DGF was associated with dialysis for >=49.25 months
      (odds ratio [OR] 2.30), donor age >=42.25 years (OR 1.77), donor end creatinine
      level >1.22 mg/dL (OR 1.94), and cold ischemia time >12 hours (OR 2.45). Of the
      55 patients with rejections, 37 (15.68%) had T-cell-mediated rejection (TCMR) and
      18 (7.63%) had antibody-mediated rejection (AMR). Nine patients (16.36%)
      exhibited graft loss, 2 (0.85%) via TCMR in the SDSA- DGF+ group and 7 (2.97%)
      via AMR, including 2 NS DGF-, 2 SDSA- DGF-, 1 SDSA- DGF+, and 2 SDSA+ DGF+
      patients. Graft survival significantly differed between the NSDGF- and SDSA- DGF+
      groups (P = .014) and between the NS DGF- and SDSA+ DGF- groups (P = .036).
      CONCLUSION: In the 7-year period following transplantation, TCMR was more
      prevalent than AMR among patients with DGF. Graft loss was less prevalent among
      patients with TCMR than among those with AMR.

PMID- 29661427
TI  - Hepatitis C Virus Eradication in Kidney Transplant Recipients: A Single-Center
      Experience in Portugal.
AB  - INTRODUCTION: Hepatitis C (HCV) is a major cause of liver impairment post-kidney
      transplantation (KT). Anti-HCV direct-acting antivirals (DAA) made viral
      eradication possible. METHODS: We performed a retrospective review of KT patients
      (n = 23) who received DAA at our hospital. Sustained viral response (SVR) was
      defined as absence of viral detection 12 weeks after cessation of therapy.
      RESULTS: From 1985 to September 2017, 1440 patients underwent transplantation at
      Hospital Santa Cruz. From a total of 32 HCV RNA+ KT recipients on follow-up, we
      describe the first 23 patients treated with DAA. They were 56.7 +/- 9.1 years
      old; 22 were white, 52.2% were males, they underwent transplantation 18.8 +/- 9.0
      years ago, and 13 had genotype 1B, 21 were naive, and 9 had stages F3/F4. All but
      2 patients, treated with grazoprevir/elbasvir, received sofosbuvir (18 with
      ledispasvir, 2 with daclastavir, and 4 with simultaneous ribavirin).
      Pretreatment, intra-treatment, and post-treatment creatinine clearances were
      61.4, 60.6, and 60.7 mL/min/1.73 m2, respectively (not significant [NS]).
      Cyclosporine A was the basis of immunosuppression in the majority [(n = 14);
      pretreatment and intra-treatment levels were 79.5 +/- 23.0 and 91.8 +/- 26.0
      ng/mL, respectively (P = .08)]; tacrolimus (n = 8) and mammalian target of
      rapamycin (mTOR) levels (n = 5) were also similar. One patient interrupted
      ribavirin after 7 weeks due to anemia; all other patients completed the treatment
      course without major side effects. Only 3 patients presented positive viral RNA
      at the fourth week of treatment and SVR was achieved in 100% of the patients 12
      weeks after treatment. CONCLUSIONS: DAA therapy was well tolerated and effective
      in 100% of our treated patients, without significant impact on the renal function
      or on the immunosuppression.

PMID- 29661428
TI  - Effects of Chronic Physical Activity on Glomerular Filtration Rate, Creatinine,
      and the Markers of Anemia of Kidney Transplantation Patients.
AB  - BACKGROUND: The incidence of anemia in kidney transplantation patients (KTPs) is
      very common and seems to be associated with the reduction in both renal function
      and physical exercise tolerance. The purpose of the present study was to compare
      biochemical markers of anemia and renal function of physically active and
      sedentary KTPs. METHOD: Serum hemoglobin (Hb), hematocrit (Hct), and serum
      creatinine (used to derive estimated glomerular filtration rate [eGFR]) were
      obtained from the medical records of 18 KTPs assisted at the Center for
      Prevention of Kidney Diseases of the Federal University of Maranhao Hospital. The
      physically active transplant patients (group 1) included 7 men and 2 women, aged
      49 +/- 14 years who participated for at least 6 months on a supervised physical
      exercise program (SPEP) (2 to 3 times a week, 90-minute sessions) and the
      sedentary counterparts (group 2) of 2 men and 7 women, aged 37 +/- 15 years.
      RESULTS: Group 1 presented higher values of Hb (14.2 +/- 2.6 vs 10.7 +/- 0.6
      g/dL; P = .003), Hct (41.6% +/- 7.0% vs 32.3% +/- 1.4%; P = .004), and eGFR (64.4
      +/- 19.4 vs 39.3 +/- 19.7 mL/min/1.73 m2; P = .015) when compared with group 2.
      There was a positive and significant correlation between Hb and eGFR (r = 0.528;
      P = .024), and between Hct and eGFR (r = .509; P = .031). CONCLUSIONS: Our
      results suggest that regular physical activity seems to improve the biochemical
      markers of anemia and also the renal function of KTPs, and these patients should
      be advised to participate in SPEP.

PMID- 29661429
TI  - Effects of a Physiotherapeutic Protocol in Respiratory Function, Aerobic Capacity
      and Quality of Life After Kidney Transplantation.
AB  - INTRODUCTION: Chronic kidney disease can lead to dysfunction of the respiratory,
      cardiac, and musculoskeletal systems, altering the body's metabolism. Renal
      transplantation and hospital physiotherapy, through specific protocols, can
      improve these dysfunctions. OBJECTIVES: This study evaluates the impact of a
      hospital physiotherapeutic protocol in quality of life (QoL), respiratory muscle
      strength, peak expiratory flow, and 6-minute walk test (6MWT) in the
      preoperative, first, and fifth days after renal transplantation. METHODS: We
      evaluated 39 patients who received a renal transplant at Clinics Hospital of
      University of Campinas for respiratory muscle strength, expiratory peak flow, and
      functional capacity by the 6MWT. The short form-36 quality of life questionnaire
      was applied to 12 patients. RESULTS: We observed a significant reduction in
      respiratory muscle strength and peak expiratory flow in the first postoperative
      day. On postoperative day 5, there was improvement in respiratory muscle strength
      and expiratory peak flow. However, aerobic capacity measured by 6MWT remained
      below predicted. Analysis of QoL showed an improvement in almost all analyzed
      domains after transplantation. CONCLUSION: A specific physiotherapeutic protocol
      applied early after transplantation provided recovery of respiratory muscle
      strength and QoL. However, longer training is necessary to obtain adequate
      aerobic rehabilitation.

PMID- 29661430
TI  - Access to Liver Transplantation in Different ABO-Blood Groups and "Exceptions
      Points" in a Model for End-Stage Liver Disease Allocation System: A Brazilian
      Single-Center Study.
AB  - BACKGROUND: In the Model for End-Stage Liver Disease (MELD) system, patients with
      "MELD exceptions" points may have unfair privilege in the competition for liver
      grafts. Furthermore, organ distribution following identical ABO blood types may
      also result in unjust organ allocation. The aim of this study was to investigate
      access to liver transplantation in a tertiary Brazilian center, regarding "MELD
      exceptions" situations and among ABO-blood groups. METHODS: A total of 465 adult
      patients on the liver waitlist from August 2015 to August 2016 were followed up
      until August 2017. Patients were divided into groups according to ABO-blood type
      and presence of "exceptions points." RESULTS: No differences in outcomes were
      observed among ABO-blood groups. However, patients from B and AB blood types
      spent less time on the list than patients from A and O groups (median, 46, 176,
      415, and 401 days, respectively; P = .03). "Exceptions points" were granted for
      141 patients (30.1%), hepatocellular carcinoma being the most common reason
      (52.4%). Patients with "exceptions points" showed higher transplantation rate,
      lower mortality on the list, and lower delta-MELD than non-exceptions patients
      (56.7% vs 19.1% [P < .01]; 18.4% vs 38.5% [P < .01], and 2.0 +/- 2.6 vs 6.9 +/-
      7.0 [P < .01], respectively). Patients with refractory ascites had a higher
      mortality rate than those with other "exceptions" or without (48%). CONCLUSIONS:
      The MELD system provides equal access to liver transplantation among ABO-blood
      types, despite shorter time on the waitlist for AB and B groups. The current MELD
      exception system provides advantages for candidates with "exception points,"
      resulting in superior outcomes compared with those without exceptions.

PMID- 29661431
TI  - Stratifying Mortality in a Model for End-Stage Liver Disease Waiting List: A
      Brazilian Single-Center Study.
AB  - BACKGROUND: The Model for End-Stage Liver Disease (MELD) system reliably predicts
      mortality in cirrhotic patients. However, the etiology of liver disease and
      presence of portal vein thrombosis are not directly taken into account in MELD
      score. Its impact on the outcomes of patients on the waiting list is still
      unclear. The aim of this study was to investigate mortality and access to
      transplantation regarding etiology of liver disease and portal vein thrombosis
      (PVT). METHODS: A total of 465 adult patients on the liver waiting list from
      August 2015 to August 2016 were followed up until August 2017. Patients were
      divided into groups according to the etiology of liver disease and presence of
      PVT. RESULTS: The most frequent etiologies were hepatitis C (26.88%), alcoholic
      cirrhosis (26.02%) and cryptogenic cirrhosis (10.75%). Death while on the waiting
      list occurred in 168 patients (36.1%) and was more frequent in nonalcoholic
      steatohepatitis (NASH, 65.4%) and alcoholic cirrhosis (41.3%). A total of 142
      (30.5%) patients underwent transplantation and viral, autoimmune, and biliary
      diseases showed higher proportion of transplantation (36.3%, 53.8%, and 34%,
      respectively; P < .01). Mean delta-MELD at the study endpoint was higher in
      patients with autoimmune hepatitis, biliary diseases, and NASH (8.3 +/- 7.2, 8.3
      +/- 9.1, and 7.5 +/- 9.1, respectively; P < .01). A total 77 patients (16.7%)
      presented PVT. There was no significant difference in outcomes between patients
      with and without PVT. CONCLUSIONS: Patients with NASH and alcoholic liver disease
      had higher mortality while on the waiting list, whereas patients with viral and
      autoimmune hepatitis had higher transplantation rate. Outcomes were not
      influenced by PVT.

PMID- 29661432
TI  - Evaluation of Lung Function in Liver Transplant Candidates.
AB  - INTRODUCTION: A wide variety of pulmonary conditions are found in cirrhotic
      patients and may compromise the pleura, diaphragm, parenchyma, and pulmonary
      vasculature, influencing the results of liver transplantation. OBJECTIVE: To
      evaluate the pulmonary function (lung capacities, volumes, and gasometric study)
      of patients with liver cirrhosis awaiting liver transplantation. PATIENTS AND
      METHODS: Cirrhotic patients, subdivided into 3 groups stratified by liver disease
      severity using the Child-Pugh-Turcotte score, were compared with a control group
      of healthy volunteers. In spirometry, the parameters evaluated were total lung
      capacity, forced volume in the first second, and the relationship between forced
      volume in the first minute and forced vital capacity. Blood gas analysis was
      performed. In the control group, arterial oxygenation was evaluated by peripheral
      oxygen saturation by pulse oximetry. RESULTS: Of the 55 patients (75% men, 51 +/-
      12.77 years), 11 were Child A (73% men, 52 +/- 14.01 years), 23 were Child B (75%
      men, 51 +/- 12.77 years), and 21 were Child C (95% men, 50 +/- 12.09 years). The
      control group had 20 individuals (50% men, 47 +/- 8.15 years). Pulmonary
      capacities and volumes by the parameters evaluated were within the normal range.
      Arterial blood gas analysis detected no hypoxemia, but a tendency to low partial
      gas pressure was noted. CONCLUSION: In this population of cirrhotic patients the
      parameters of spirometry were normal in relation to the lung capacities and
      volumes in the different groups. No hypoxemia was detected, but a tendency to
      hypocapnia in the blood gas was noted.

PMID- 29661433
TI  - Better Selection Criteria With Prognostic Factors for Liver Transplantation.
AB  - BACKGROUND: Liver transplantation has evolved significantly in recent years, with
      each advancement part of the effort toward increasing patient and graft survival
      as well as quality of life. The objective of this study was to evaluate the
      prognostic factors and selection criteria for liver transplantation. METHODS: Our
      study was a statistical analysis, logistic regression, and survival evaluation of
      a total of 80 liver transplants that were performed between June 1, 2016 and
      September 24, 2016. Recipient factors evaluated included age, retransplantation,
      hemodialysis, cardiac risk, portal vein thrombosis, hospitalization, fulminant
      hepatitis, previous surgery, renal failure, and Model for End-stage Liver Disease
      (MELD) score. Donor factors included age, cardiac arrest, acidosis, days in the
      intensive care unit, steatosis, and vasoactive drug use. RESULTS: Of the 80
      patients transplanted, 65 deceased donor liver transplants (DDLTs) and 15 living
      donor liver transplants (LDLTs) were performed. LDLT overall 1-year patient
      survival was 77.5% and graft survival 75%, and DDLT overall patient survival was
      89.23% and graft survival was 86.15%. On evaluated score criteria analyzed we
      observed a significant score on recipient (P = .01) and not significant on donor
      (P =.45). Isolated factors evaluated included recipient age (relative risk [RR]
      3.15, 95% confidence interval [CI] 0.89 to 11.09; P = .074), retransplant (RR
      4.22, 95% CI 1.36 to 13.1; P = .013), and hemodialysis (RR 4.23, 95% CI 1.45 to
      12.31, P = .008). On donor evaluation, we observed moderate and severe steatosis
      (RR 3.8, 95% CI 0.86 to 16.62; P = .06). CONCLUSION: In conclusion, we
      demonstrate a relevant model of criteria selection of liver transplant patients
      that is able to make a better match between the donor and recipient allocation
      for a better graft and patient survival.

PMID- 29661434
TI  - Daclatasvir and Sofosbuvir With or Without Ribavirin in Liver Transplant
      Recipients: A Single-Center Real-World Study.
AB  - BACKGROUND: Treatment with direct-acting antiviral drugs in interferon-free
      regimens is currently recommended for viral hepatitis C recurrence after liver
      transplantation. There are limited data regarding its results in this population,
      and no optimal treatment scheme has yet been singled out. METHODS: We report our
      real-world results in liver transplant (LT) recipients. All patients were
      hepatitis C virus (HCV) monoinfected and completed a 12-week treatment course,
      followed 12 weeks later by HCV polymerase chain reaction testing with 12 IU/mL
      sensibility. Liver fibrosis was graded with the use of biopsies taken <12 months
      before treatment and stratified as early (0-1) or moderate to advanced (2-4)
      according to the Metavir score. RESULTS: Median postoperative time was 5.2 years.
      Genotype 3 was found in 66.7% of the sample. The following regimens were
      prescribed: daclatasvir-sofosbuvir with (n = 11) or without (n = 28) ribavirin.
      Genotypes 1 and 3 were evenly distributed between the regimens. Sustained
      virologic response (SVR) was obtained in 24 out of 28 patients (85.7%) who
      received daclatasvir-sofosbuvir and in all patients (100%) who received
      daclatasvir-sofosbuvir-ribavirin (global SVR 89.7%). All patients that failed
      treatment had genotype 3 HCV. Fibrosis was evaluated in 79.5% of the sample:
      48.4% had early and 51.6% had moderate to advanced fibrosis, for which ribavirin
      was more commonly prescribed (P = .001). CONCLUSIONS: The SVR rate in our LT
      recipients was similar to that previously reported in the literature. The
      addition of ribavirin to DAA treatment appears to be justified in this
      population.

PMID- 29661435
TI  - Transient Elastography in Acute Cellular Rejection Following Liver
      Transplantation: Systematic Review.
AB  - BACKGROUND: Transient elastography (TE) is a noninvasive technique that measures
      liver stiffness. When an inflammatory process is present, this is shown by
      elevated levels of stiffness. Acute cellular rejection (ACR) is a consequence of
      an inflammatory response directed at endothelial and bile epithelial cells, and
      it is diagnosed through liver biopsy. This is a systematic review of the
      viability of TE in ACR following liver transplantation. METHODS: The Cochrane
      Library, Embase, and Medline PubMed databases were searched and updated to
      November 2016. The MESH terms used were "Liver Transplantation," "Graft
      Rejection," "Elasticity Imaging Techniques" (PubMed), and "Elastography"
      (Cochrane and Embase). RESULTS: Seventy studies were retrieved and selected using
      the PICO (patient, intervention, comparison or control, outcome) criteria. Three
      prospective studies were selected to meta-analysis and evaluation. A total of 33
      patients with ACR were assessed with TE. One study showed a cutoff point of >7.9
      kPa to define graft damage and <5.3 kPa to exclude graft damage (receiver
      operating characteristic 0.93; P < .001). Another study showed elevated levels of
      liver stiffness in ACR patients. However, in this study, no cutoff point for ACR
      was suggested. The final prospective study included 27 patients with ACR at liver
      biopsy. Cutoff points were defined as TE > 8.5 kPa, moderate to severe ACR, with
      a specificity of 100% and receiver operating characteristic curve of 0.924. The
      measurement of TE < 4.2 kPa excludes the possibility of any ACR (P = .02).
      CONCLUSIONS: TE may be an important tool for the severity of ACR in patients
      following liver transplantation. Further studies should be performed to better
      define the cutoff points and applicability of the exam.

PMID- 29661436
TI  - Model for End-Stage Liver Disease Score Before Hepatic Transplantation and Root
      Mean Square of the Diaphragmatic Domes Affect Postoperative Extubation Time.
AB  - INTRODUCTION: The liver transplantation procedure, in addition to its prolonged
      surgical time, also predisposes to complications such as changes in respiratory
      mechanics, lung volumes, and gas exchange. OBJECTIVE: This study aims to verify
      if clinical factors related to the recipient, namely immediate pretransplant
      Model for End-Stage Liver Disease (MELD) score, surgical time, and root square
      metric (RMS) of the diaphragmatic domes, affect the extubation time after liver
      transplantation. METHOD: A prospective study, with a sample collected for
      convenience, gathered age (years), sex (male or female), MELD score immediately
      prior to transplantation (without the addition of special situation scores), and
      surgical time and time for extubation (in minutes). The latter were obtained from
      the physiotherapy team records, and surface electromyography was performed within
      30 minutes after elective extubation, by a single researcher, with supplemental
      oxygen support, maintaining SpO2 >= 95% and following protocol of positioning and
      acquisition of electromyographic signals based on the study of Oliveira et al
      (2012). RESULTS: For the 21 patients studied, the RMS of the left dome showed a
      moderate-intensity correlation (-0.56) with the time of extubation, and linear
      multiple regression model the left dome (P = .013) and preoperative MELD score (P
      = .048) showed significant correlation with extubation time. CONCLUSION: The
      preoperative MELD score and the RMS values of the left dome significantly
      correlate with the time for patient extubation after liver transplantation,
      showing the effect of previously acquired muscle weakness and preoperative MELD
      score on postoperative outcome.

PMID- 29661437
TI  - Development of Routine Dental Care for Liver Transplant Outpatients.
AB  - BACKGROUND: Liver transplantation has become commonplace for patients with end
      stage liver disease. The liver is a bodily organ of great importance, and its
      dysfunction can cause significant complications throughout the body. Patients
      with hepatic disease should be able to acquire knowledge of the physiology of the
      liver via the dental profession, and it is also necessary to modify some aspects
      of dental treatment even in healthy patients. Problems such as excessive bleeding
      and hepatotoxicity caused by some of the drugs used in dental treatment can lead
      to a decrease in systemic health. Otherwise, patients with liver disease will
      have poorer oral health than the general population. Thus, it is important to
      have well-established routine dental care in this patient group and offer
      management of oral health in view of the effects of liver disease. METHODS: The
      objective of this work was to undertake a bibliographic review of the dental
      approaches to patients with liver disease and liver transplant recipients and to
      propose a dental care routine for such patients in an outpatient setting.
      RESULTS: A search was carried out on the main scientific databases (PubMed,
      Medline, and SciELO) for publications related to this subject and, particularly
      those published after 2010. The articles selected describe poor oral hygiene
      among patients, independent of the etiology of their liver disease. These
      patients also had a high index of xerostomia, caries, periodontal disease, apical
      lesions, and fungical infections. To control bleeding during and after surgery,
      hemostatic measures must be understood and adopted. CONCLUSION: There are no data
      about routine dental care among liver disease/transplantation patients. Thus, our
      findings will hopefully encourage other services to structure their approaches
      and consider enhancing their dental care protocols for patients with liver
      related complications.

PMID- 29661438
TI  - Clinical Profile of Patients With Diabetes Mellitus and Liver Transplantation:
      Results After a Multidisciplinary Team Intervention.
AB  - BACKGROUND: Over the years, survival after liver transplantation has increased
      and metabolic complications are becoming more common, contributing to patients'
      morbidity and mortality. The objectives of this study were to describe a
      population of patients with hepatic transplantation and diabetes mellitus (DM),
      evaluate the frequency of metabolic complications, and assess the impact of a
      multidisciplinary team on DM management. MATERIALS AND METHODS: This was a
      retrospective study involving interview and medical record analysis of 46
      consecutive patients followed at the diabetes mellitus and liver transplantation
      unit of a tertiary university hospital, all evaluated by a multidisciplinary
      team. RESULTS: Of all patients, 76.1% were men, with a median age 60 years old
      (interquartile range: 56 to 65 years) and liver transplantation time of 5 years
      (interquartile range: 0.6-9 years). Hypertension, hypercholesterolemia,
      hypertriglyceridemia, alcoholism, and smoking were present in 47.8%, 34.8%,
      23.9%, 34.8%, and 30.4% of the patients, respectively. The most frequent
      immunosuppressant in use was tacrolimus (71.1%). Regarding nutritional status,
      37.9% of patients were classified as overweight according to body mass index, and
      41.2% were considered overweight according to the triceps skin fold. The median
      glycosylated hemoglobin and weight before and after intervention of the
      multidisciplinary team in all 46 patients were, respectively, 7.6% (5.7% to 8.8%)
      versus 6.5% (5.7% to 7.7%); P = .022 and 70.5 kg (64.7 to 82.0 kg) versus 71.6 kg
      (65.0 to 85.0 kg); P = .18. CONCLUSIONS: Hypertension and dyslipidemia were
      common in transplanted patients with DM. Intervention of the multidisciplinary
      team resulted in a significant improvement in glycosylated hemoglobin without
      significant weight gain.

PMID- 29661439
TI  - Frequency of Thyroid Dysfunction in Patients With Diabetes Mellitus Before and
      After Liver Transplantation.
AB  - BACKGROUND: There is mutual influence between the liver and thyroid hormone
      metabolism. Patients with diabetes mellitus (DM) also have an increased
      prevalence of thyroid disorders (TDs). The objectives of this study were to
      evaluate the frequency of TD before and after liver transplantation (LT) in a
      population of patients with DM as a whole and when categorized by sex. MATERIALS
      AND METHODS: This was a retrospective study involving interview and medical
      record analysis of 46 consecutive patients followed at the diabetes mellitus and
      liver transplantation unit of a tertiary university hospital. RESULTS: Of all
      patients, 76.1% were men with a median age of 60 years old (interquartile range:
      56 to 65 years) and time since LT of 5 years (range, 0.6 to 9 years).
      Hypertension, hypercholesterolemia, hypertriglyceridemia, alcoholism, and smoking
      were present in 47.8%, 34.8%, 23.9%, 34.8%, and 30.4% of the patients,
      respectively. The most frequent immunosuppressant in use was tacrolimus (71.1%).
      TD was present in 4.3% and 13% before and after LT, respectively (P = .058). In
      women and men, these frequencies were 9.1% and 18.2% (P = .563), and 2.9% and
      11.8% (P = .045), respectively. CONCLUSIONS: Frequency of TD was high both before
      and after LT. After transplantation, prevalence of TD increased in men and
      differences between males and females almost disappeared. Further studies are
      needed to assess if screening for TD before and after LT in patients with DM
      might be beneficial, especially in men.

PMID- 29661440
TI  - Renopancreatic Transplantation: Evaluation of 15 Years in 131 Patients.
AB  - BACKGROUND: The most common multiple-organ transplant is the simultaneous
      pancreas-kidney transplantation (SPK). It is usually offered to patients who have
      insulin-dependent diabetes mellitus and those with diabetic nephropathy and renal
      failure that has already been established. In this study we present the results
      of 15 years of SPK in a transplant hospital center in Parana, Brazil, and
      evaluated survival, immunosuppression, and transplant-related problems. METHODS:
      This study was a retrospective analysis of 131 SPK transplants performed at the
      Angelina Caron Hospital between January 2001 and December 2015. RESULTS: The mean
      age of SPK recipients was 34 years, with slight a predominance of males (50.4%).
      Mean graft ischemia time was 11 hours. Exocrine drainage was predominantly
      vesical, but this approach was abandoned after 2011. As for immunosuppression,
      induction was performed with basiliximab or thymoglobulin and maintained with
      prednisone, mycophenolate mofetil, tacrolimus, and/or sirolimus. Patient survival
      increased from 68.1% in 2001 to 2005 to 77.6% in 2011 to 2015. Graft survival at
      the end of the period was 85.7% for kidney and 75.5% for pancreas. The main
      surgery-derived problems for pancreas and kidney was thrombosis (15% and 6%,
      respectively). The main clinical problems were rejection of the pancreas (18.3%)
      and urinary infection of the kidney (33.3%). The main cause of death was intra
      abdominal sepsis (11.4%). CONCLUSION: There was an improvement in survival rates
      over the time frame observed, but it remains necessary to adopt measures to
      reduce transplant-derived problems, including review of the antibiotic therapy
      protocol and measures to avoid graft thrombosis.

PMID- 29661441
TI  - Clinical Evolution of Patients Using Ventricular Assist Devices as a Bridge for
      Transplantation.
AB  - OBJECTIVE: To evaluate the clinical evolution of patients with implantation of
      ventricular assist device (VAD) and identify the intervening factors for death.
      METHODS: This analytical, retrospective study was carried out in a public
      reference hospital in cardiopulmonary diseases located in northeastern Brazil.
      The study population encompassed the medical records of 16 patients who underwent
      VAD implantation. Data collection took place from January to August 2016, through
      the consultation of medical records. Descriptive analysis, odds ratio, and the
      Fisher's Exact, Wilcoxon, Friedman and t-tests were used to analyze the data.
      RESULTS: All patients experienced complications during the use of the device,
      with bleeding being the main cause (11 [68.8%]). There was a significant decrease
      in noradrenaline (P = .025), milrinone (Primacor; P = .007), and dobutamine (P =
      .046) flow rates with the clinical evolution of patients. Regarding hematologic
      parameters, the use of VAD promoted a significant improvement in hemoglobin (P <
      .001), hematocrit (P = .003), activated partial thromboplastin time (P = .013),
      and fibrinogen (P = .049) values at the 3 time points analyzed. Regarding the
      clinical outcome of the patients, the majority (10 [62.5%]) underwent cardiac
      transplantation. CONCLUSIONS: This study allowed for better knowledge of the
      clinical evolution of patients with VAD implantation, highlighting the benefits
      of this type of device as a bridge for heart transplantation.

PMID- 29661442
TI  - Weight Gain and Acute Rejection in Patients Submitted to Pulmonary
      Transplantation: A Retrospective Cohort of 10 Years.
AB  - OBJECTIVE: Acute rejection is one of the most common complications after
      pulmonary transplantation. The aim of this work was to verify the association of
      nutritional status and weight gain with acute rejection in the recipient during
      the 1st year after pulmonary transplantation. METHODS: Retrospective cohort study
      with patients submitted to pulmonary transplantation at a pulmonary
      transplantation center in the state of Sao Paulo. Data on sex, age, underlying
      disease, type of transplantation, and presence, degree, and frequency of
      rejection according to the transbronchial biopsy results were collected, along
      with body mass index (BMI) and weight variation over the course of 1 year. The
      difference between groups was analyzed by means of Student t test and the
      association by means of chi-square test. Significance was considered with P <
      .05. RESULTS: A total of 117 patients were included, of which 71 (60.7%) were
      male. The average age was 39.8 +/- 15.5 years. There were 77.8% with acute
      rejection in the 1st year after transplantation. The nutritional status of
      eutrophy prevailed according to BMI in both adolescents and adults, with no
      association with acute rejection (P = .80), and there was a greater weight gain
      among the individuals who showed rejection, with an increase of 7.58 kg (95%
      confidence interval [CI] 6.35-8.81) compared with those who did not present
      rejection, whose average weight gain was 4.12 kg (95% CI 1.28-6.95; P = .01).
      CONCLUSIONS: Nutritional status was not associated with acute cell rejection in
      the 1st year after transplantation, although weight gain was greater in those who
      had rejection.

PMID- 29661443
TI  - Cyclosporine Versus Tacrolimus: Which Calcineurin Inhibitor Has Influence on
      Cytomegalovirus Infection in Cardiac Transplantation?
AB  - INTRODUCTION: Cytomegalovirus (CMV) infection is a relevant cause of morbidity
      and mortality in transplantation patients. Its major incidence is in the first
      year and viral replication is related to acute rejection, survival reduction, and
      graft vascular disease. OBJECTIVE: This study aims to evaluate retrospectively
      whether a high dose of calcineurin inhibitors correlates with CMV-positive
      polymerase chain reaction (PCR), need for treatment, and death in cardiac
      transplantation patients. METHODS: This is a case-control study including
      patients who underwent transplantation between 2014 and 2016. They were separated
      into two groups (positive or negative PCR) and evaluated for dosage serum levels
      of cyclosporine and tacrolimus. Patients were classified with adequate dose of
      immunosuppressant or high dose, and was analyzed that there was any association
      with those and positive CMV-PCR, need for treatment for CMV, and deaths. For
      statistical analysis, the Student t test was used for the quantitative variables
      and the Fisher's Exact Test for qualitative variables. To show CMV-free survival,
      the Kaplan-Meier curve was used. The level of significance was set at 5%.
      RESULTS: CMV-positive PCR in the sample was 72% for a total of 50 individuals.
      Positive PCR correlated with a high dose of calcineurin inhibitors in a
      statistically significant way (P = .002), as did a high dose of cyclosporine (P =
      .004); however, a high dose of tacrolimus had no such association (P = .17). When
      a high dose was assessed with a need for treatment, the chance of needing
      treatment increased more than eight times (P = .024; odds ratio = 8.25; 95% CI =
      1.33 to 51.26), which was different from results found with high-dose tacrolimus
      (P = 1.0). However, no significant association was found in relation to deaths.
      CONCLUSIONS: Tacrolimus serum levels showed no association with CMV-PCR, which
      was different from serum cyclosporine, which showed association with CMV-PCR
      positivity, increasing the need for treatment approximately 8-fold, without
      association with death.

PMID- 29661444
TI  - Single- and Double-Lung Transplantation: Results of an Initial Experience of 39
      Cases in Ceara (Northeast Brazil).
AB  - INTRODUCTION: The lung transplantation (LTx) program began in Ceara in 2011 and
      the first LTx was performed on June 11, 2011. The aim of this study was to
      present the initial results of the 6-year experience of our program. METHODS: We
      retrospectively reviewed our experience on LTx from June 2011 to August 2017.
      Data on recipients and transoperative and postoperative outcomes were recorded in
      a database. RESULTS: Twenty-two (56.4%) were single LTx, 15 (38.5%) were double,
      and 2 (5.1%) bilateral lobar. The mean age was 47.5 +/- 15 years, and 26 (66.7%)
      were men. Twenty-eight (71.8%) had pulmonary fibrosis; 5 (12.8%) had pulmonary
      emphysema, 3 (7.7%) had bronchiectasis; 2 (5.1%) had pulmonary hypertension, and
      1 (2.6%) had lymphangioleiomyomatosis. Complications occurred in 82% (32/39) and
      in-hospital mortality was 30.8% (single LTx = 27.8% and double LTx = 33.3%). The
      main complications were infection in 17 (43.5%) cases and primary graft
      dysfunction in 7 (17.9%). There was a significant improvement in pulmonary
      function in the first year of follow-up (forced expiratory volume pre-LTx = 37%
      +/- 16% and 12 months post-LTx = 72% +/- 22%, P = .001); and overall survival at
      36 months was 59.0%, with no difference between single- and double-lung
      transplants. CONCLUSIONS: Idiopathic pulmonary fibrosis was the most common
      underlying disease and single LTx was the most commonly performed operation.
      There was a high incidence of postoperative complications and in-hospital
      mortality, but the 36-month follow-up showed a marked improvement in lung
      function and a global survival similar to the literature.

PMID- 29661445
TI  - Epidemiologic Profile of Patients Transplanted With Hematopoietic Stem Cells in a
      Reference Service in the State of Rio Grande do Norte, Brazil.
AB  - BACKGROUND: Hematopoietic stem cell transplantation (HSCT) consists of the
      intravenous infusion of healthy hematopoietic stem cells to restore the medullary
      and immunologic function of patients affected by a series of hematologic,
      oncologic, immunologic, malignant and nonmalignant inherited or acquired
      diseases, with the possibility of cure or increase of disease-free survival.
      OBJECTIVE: To characterize the epidemiologic profile and the cases of death of
      patients who underwent HSCT. METHODS: This is a cohort quantitative study, nested
      with a retrospective, descriptive, and analytical study of a hospital-based
      cohort that included the patients who underwent HSCT at a referral service in the
      state of Rio Grande do Norte, a region of northeastern Brazil. RESULTS: There was
      a slight male prevalence (52.94%), the age of the patients ranged from 2 to 73
      years old, 18.38% were brown, 47.06% were married, 15.07% were students, 78.31%
      had a diagnosis of multiple myeloma, 93.38% developed gastrointestinal
      toxicities, all patients received chemotherapeutic treatment, 54.78% had
      allogeneic HSCT, and the cause of the most recorded deaths was septic shock
      (48.19%). CONCLUSIONS: This study showed relevant scientific evidence on the
      clinical and epidemiologic profile of patients who underwent HSCT. In general,
      sociodemographic data are similar to national and international research results.

PMID- 29661446
TI  - Multivisceral Transplantation Rehabilitation Program-Case Report.
AB  - Multivisceral transplantation is the treatment for multiple abdominal organ
      failure. The patient experiences reduced food intake and absorption of nutrients,
      contributing to weight loss and decreased muscle mass, reducing functional
      capacity. A physical and nutritional rehabilitation program based on adequate
      caloric intake associated with supervised physical exercise seems to support a
      gain of muscle mass, re-establishing its capacity and functional independence. A
      rehabilitation program was carried out, consisting of low-intensity aerobic
      exercise on treadmill, exercises of global strengthening (50% of 1 maximum
      repetition [1RM], with progressive increase), and nutritional monitoring (oral
      hypercaloric diet, hyperproteic supplementation daily and after exercise).
      Initial and final evaluation included weight, muscle mass index, brachial
      circumference (BC), tricipital cutaneous fold (TCF), hand grip strength (HGS), 6
      minute walk test (6MWT), 1RM, vital capacity (VC), and respiratory muscle
      strength. After the program, functional capacity was evaluated through the 6MWT
      (92%), 1RM test, VC (55%), respiratory muscle strength, HGS at 5 kg, weight gain
      (4.75%), increase of BC in 2 cm, and TCF in 2 mm. The program contributed to
      functional independence, improved quality of life, and social reintegration,
      suggesting the importance of a supervised physical activity program associated
      with adequate nutritional intake after multivisceral transplantation.

PMID- 29661448
TI  - Epidemiologic Profile of Transplant Patients Treated by the Physiotherapy.
AB  - Transplant candidates have advanced chronic disease, which often leads to
      muscular and respiratory impairment contributing to reduced quality of life and
      daily life activities, and these patients are therefore referred to physiotherapy
      service. Because of this, it is necessary to know the epidemiologic and
      functional profile for a better physiotherapeutic approach. Inpatients of kidney,
      liver, heart, lung and multivisceral transplantation programs were followed up
      for 1 year. A comparative analysis between groups was performed, taking into
      account hospital stay time and functional independence measure (FIM). In all, 157
      patients (88 post-transplant) were evaluated, with mean age of 54 years, and 99
      were men. Prevalence of transplantation included liver: 87 (56%); kidney: 51
      (32%); heart: 10 (6%); lung: 8 (5%); multivisceral: 1 (1%). The average length of
      hospital stay was 23 days for kidney patients, 19 days for lung patients, 18 days
      for heart patients, 15 days for liver patients, and the 15 days for multivisceral
      patients. The mean of FIM score was 94 for heart patients; 95 for liver patients,
      96 for kidney patients, 99 for lung patients, and 120 for multivisceral patients.
      The highest incidence of hospitalization was of liver patients, although renal
      patients had a longer time of hospitalization. FIM score was higher at hospital
      discharge, if compared with the values at the moment of evaluation, but through
      the comparison of FIM previous with FIM final scores, the patients still
      presented functional limitation at the time of hospital discharge. Specific
      protocols for each transplant group, focused on the improvement of the
      functionality, are necessary.

PMID- 29661447
TI  - Chronological Factors of the Process of Donation and Classification of Corneal
      Tissue.
AB  - INTRODUCTION: The quality of corneal tissue is influenced by several factors
      inherent to the recipient, donor, donation process, and transplantation that may
      primarily or secondarily interfere in the survival of a corneal graft. OBJECTIVE:
      The objective of this study was to identify the factors inherent to the donation
      process, specifically related to the harvesting and processing of tissue and to
      the donor, that may interfere with the quality of corneal tissue. MATERIALS AND
      METHODS: This was a cross-sectional, descriptive, and analytical study carried
      out from January to April 2015 at the Onofre Lopes University Hospital, Natal/RN,
      Brazil. A survey of the keratoplasties performed between the years 2010 and 2014
      was carried out, totaling 258 donated corneas. RESULTS: The mean age of donors
      was 42.08 years, ranging from 2-80 years. As for quality, 64.45% of the corneas
      were classified as good, 23.05% as regular, 11.33% as poor, and 1.17% as
      excellent. The mean time between death and preservation was approximately 7 hours
      and 15 minutes, and the mean time elapsed until use was 10 days after immersion
      in preservation medium. DISCUSSION AND CONCLUSIONS: Factors inherent in the
      donation process that may interfere with the quality of the corneal graft
      correspond to factors of a chronological nature: donor age and time elapsed
      between death and preservation of the graft.

PMID- 29661449
TI  - Genetic Mechanisms Involved in the Generation of HLA Alleles in Brazilians:
      Description and Comparison of HLA Alleles.
AB  - BACKGROUND: The HLA genes show high levels of diversity as indicated by the
      number of HLA alleles. There are almost 11,000 classical HLA-A, -B, -DRB1 alleles
      in populations around the world, making the search for compatible donors
      difficult. HLA diversity is generated by different genetic mechanisms, such as
      point mutations, which result in single nucleotide polymorphisms, insertion and
      deletion, and recombination. The aim of this study was to describe genetic
      mechanisms involved in the generation of HLA alleles in Brazilians. METHODS:
      Twenty-six alleles indentified in the Brazilian bone marrow donors were include
      in the study. Data regarding new HLA alleles by sequence-based typing were also
      used to elucidate what genetics mechanism was involved in the HLA variability.
      The new alleles were officially named by the World Health Organization
      Nomenclature Committee. RESULTS: The new alleles described were HLA
      DRB1*11:04:14, HLA-A*33:117, and HLA-B*41:48. The DRB1*11:04:14 allele was
      generated by synonymous point mutation at codon 48. The A*33:117 allele was
      generated by nonsynonymous nucleotide mutation leading to amino acid substitution
      at codon 74. The B*41:48 allele was generated by an intralocus gene conversion
      between the HLA alleles from groups HLA-B*13, B*35, B*53, or B*58 and an allele
      from the HLA-B*41 group. CONCLUSIONS: Different genetic mechanisms introduce new
      mutant HLA alleles into the human population requiring attentive and rigorous
      specialists and the use of different methodologies to identify these mutations in
      HLA typing routine.

PMID- 29661450
TI  - Effect of Hepatic Preconditioning with the Use of Methylene Blue on the Liver of
      Wistar Rats Submitted to Ischemia and Reperfusion.
AB  - BACKGROUND: The liver may be injured in situations where it is submitted to
      ischemia, such as partial hepatectomy and liver transplantation. In all cases,
      ischemia is followed by reperfusion and, although it is essential for the
      reestablishment of tissue function, reperfusion may cause greater damage than
      ischemia, an injury characterized as ischemia-reperfusion (I/R) damage. The aim
      of this work was to analyze the effect of ischemic preconditioning with the use
      of methylene blue (MB; 15 mg/kg) 5 or 15 minutes before I/R (IRMB5' and IRMB15',
      respectively) on the hepatic injury occurring after I/R. METHODS: Twenty-eight
      male Wistar rats were used, and liver samples submitted to partial ischemia (IR)
      or not (NI) were obtained from the same animal. The samples were divided into 7
      groups. Data were analyzed statistically by means of the nonparametric Mann
      Whitney test and Wilcoxon Matched test, with the level of significance set at 5%
      (P < .05). RESULTS: The rate of oxygen consumption by state 3 mitochondria was
      inhibited in all ischemic groups compared with the sham group (SH vs IR: P =
      .0052; SH vs IRMB5': P = .0006; SH vs IRMB15': P = .0048), which did not occur in
      the nonischemic contralateral portion of the same liver (SH vs NI: P = .7652; SH
      vs NIMB5': P = .059; SH vs NIMB15': P = .3153). The inhibition of the rate of
      oxygen consumption by state 3 mitochondria was maintained in the presence of MB
      (IR vs IRMB5': P = .4563; IR vs IRMB15': P = .9021). The respiratory control
      ratio was reduced in all ischemic groups compared with the sham group, owing to
      the inhibition of oxygen consumption in state 3 (SH vs IR: P = .0151; SH vs
      IRMB5': P = .005; SH vs IRMB15': P = .0007). CONCLUSIONS: Methylene blue had no
      effect on the mitochondrial respiratory parameters studied, but was able to
      reduce lipid peroxidation, preventing the production of reactive oxygen species
      (SH vs IRMB15': P = .0210).

PMID- 29661451
TI  - Ischemia With Preconditioning in Wistar Rats Maintains Mitochondrial Respiration,
      Even With Mild Hepatocellular Disturbance.
AB  - INTRODUCTION: In hepatectomy or liver transplantation, preconditioning is a
      procedure indicated to protect the organ from ischemia-reperfusion injury (I-R).
      OBJECTIVE: Evaluate the effect of preconditioning after hepatic I-R in Wistar
      rats, through mitochondrial respiration, liver histology, and profile. METHOD:
      Twenty male Wistar rats, weighing on average 307.1 g, were anesthetized with
      sodium thiopental (25 mg/kg) intravenously and xylazine hydrochloride (30 mg/kg)
      intramuscularly. The animals were divided into 2 groups: the preconditioning
      group (PCG), which contained 10 animals, and the hepatic pedicle was isolated and
      submitted to clamping with microvascular clamp (10 minutes of ischemia and 10
      minutes of reperfusion, followed by 30 minutes of ischemia and 30 minutes of
      reperfusion); and the simulated operation group (SOG), which contained 10 animals
      submitted to manipulation of the hepatic pedicle and observation for the same
      length of time, with blood collected for transaminase dosage measurements, and
      liver biopsy for evaluation of mitochondrial respiration and histologic liver
      analysis and after sacrificed under anesthesia. The project was approved by the
      Ethics Committee on Animal Experimentation CEEA/UNICAMP under protocol number
      3905-1. RESULT: The PCG mitochondria showed the same respiration level as the
      SOG, when stimulated with the addition of adenosine diphosphate or carbonyl
      cyanide p-trifluoromethoxyphenylhydrazone. In the respiratory control ratio and
      resting of velocity of respiration the groups behaved in a similar way. The PCG
      presented high aspartate and alanine transaminases (P < .03) and about 60% of
      sinusoidal congestion and venous congestion in the histologic analysis when
      compared with SOG. CONCLUSION: We found that ischemia with preconditioning in
      Wistar rats can lead to mild histologic and biochemical dysfunction without
      leading to impairment of mitochondrial respiration.

PMID- 29661452
TI  - Staphylococcus Infection-Associated Glomerulonephritis in a Kidney Transplant
      Patient: Case Report.
AB  - BACKGROUND: Staphylococcus infection-associated glomerulonephritis is a rare
      cause of graft dysfunction in kidney transplant. Suspicion should be high in the
      setting of elevation of serum creatinine, active urinary sediment, with or
      without hypocomplementemia, and simultaneous Staphylococcus aureus infection. A
      kidney biopsy is usually diagnostic. CASE REPORT: A 56-year-old man, who received
      a kidney transplant in 1998, with basal serum creatinine of 1.2 mg/dL and normal
      urinary sediment, was admitted to our kidney transplantation unit with graft
      dysfunction and a urinary tract infection caused by S aureus with septicemia,
      treated with antibiotics, in the context of recently intensified
      immunosuppression for a primary immune thrombocytopenia diagnosed 3 weeks
      earlier. After antibiotic treatment, the patient persisted with graft
      dysfunction, edema, and hypertension, with a S aureus isolation in the urine
      culture, active urinary sediment, and low C3. A kidney biopsy was performed,
      showing diffuse proliferative endocapillary and mesangial glomerulonephritis,
      with IgA(++) and C3(++) mesangial and endocapillary deposits in
      immunofluorescence. The patient was treated symptomatically and maintained his
      regular immunosuppression. At the last follow-up, his serum creatinine value was
      stable at 2.5 mg/dL. CONCLUSIONS: The onset of a nephritic syndrome with a
      simultaneous S aureus infection should lead to suspicion of this uncommon entity,
      confirmed histologically. Despite its association with poor graft survival, our
      patient's graft survival remained stable.

PMID- 29661453
TI  - Late-Onset Post-transplantation Central Nervous System Lymphoproliferative
      Disorder: Case Report.
AB  - Post-transplantation lymphoproliferative disorder (PTLD) is a heterogeneous group
      of conditions that complicate organ transplantation and are due to
      immunosuppression. Central nervous system (CNS)-PTLD is rare but its incidence is
      increasing. It often occurs late and is associated with kidney transplantation
      and Epstein-Barr virus (EBV) infection. Outcomes are poor. We present the case of
      a 77-year-old white male who received a cadaveric kidney transplant in 2003.
      Maintenance immunosuppression consisted of mycofenolate mofetil (MMF),
      cyclosporine, and prednisolone. In 2017, while admitted for other cause, he
      presented with de novo epileptic seizures. Because the patient had a pacemaker,
      magnetic resonance imaging (MRI) could not be performed. The final diagnosis of
      CNS-PTLD was known through brain biopsy, after a suitable image was obtained with
      contrasted brain computed tomography (CT). EBV was positive in brain biopsy,
      cefalospinal fluid, and blood. Treatment was attempted with reduction of
      immunosuppression. Cyclosporine was switched to sirolimus. The patient died
      before administration of rituximab. The patient's performance status was poor.
      There must be awareness for neurological symptoms after kidney transplantation to
      timely diagnose CNS-PTLD. Contrasted brain CT may be useful to obtain a biopsy
      specimen in cases where MRI is impossible to use.

PMID- 29661454
TI  - Successful Treatment of Strongyloides stercoralis Hyperinfection in a Kidney
      Transplant Recipient: Case Report.
AB  - Strongyloides stercoralis (SS) can cause hyperinfection and disseminated
      infection in immunosuppressed individuals, with risk of mortality. We report the
      case of a cadaveric kidney transplant recipient who developed gastrointestinal
      symptoms and eosinophilia, approximately 3 months after transplantation. Stool
      examination and esophagogastroduodenoscopy with biopsies were positive for SS
      larvae. The patient was started on oral ivermectin and immunosuppression was
      reduced, but still the clinical picture got worse with metabolic ileus and
      respiratory symptoms, with the need for administration of subcutaneous ivermectin
      and combined therapy with albendazol. The patient survived and graft function was
      preserved. The patient was unlikely to be the source of infection. We also
      present a review of cases of SS infection in kidney transplant recipients.

PMID- 29661455
TI  - Management of Juvenile Idiopathic Arthritis in ABO-incompatible Kidney
      Transplantation: A Case Report.
AB  - Biologic agents are a beneficial therapy for juvenile idiopathic arthritis (JIA).
      However, there is a lack of evidence with regard to management of these agents
      for JIA patients who undergo kidney transplantation (KTx). A 36-year-old woman
      with JIA who was treated with tocilizumab targeting interleukin-6 (IL-6) receptor
      underwent ABO-incompatible kidney transplantation (ABOi KTx). To prevent over
      immunosuppression, tocilizumab was discontinued before ABOi KTx. Rituximab,
      tacrolimus, mycophenolate mofetil, everolimus, and methylprednisolone were used
      for immunosuppression. Clinical remission of joint pain was maintained for over 3
      years despite complete discontinuation of tocilizumab. Both serum IL-6 and
      soluble IL-6 receptor levels were markedly decreased, suggesting that
      multitargeted immunosuppression for ABOi KTx induced long-term clinical remission
      of JIA through inhibition of the IL-6 pathway. However, levels of C-reactive
      protein (CRP) and matrix metalloproteinase-3 (MMP-3) gradually increased
      thereafter and abatacept was initiated to prevent joint deterioration. These
      levels decreased without any adverse events. The patient's renal graft function
      was well maintained.

PMID- 29661456
TI  - Severe Renal Allograft Rejection Resulting from Lenalidomide Therapy for Multiple
      Myeloma: Case Report.
AB  - Lenalidomide, a thalidomide analogue, is an immunomodulatory drug currently used
      as a chemotherapeutic agent in treating certain hematologic malignancies,
      including multiple myeloma. The antineoplastic effect of lenalidomide may be due
      to its ability to modulate different components of the immune system as well as
      its antiangiogenic, antiproliferative, and direct cytotoxic activity. Given its
      immunomodulatory effects, lenalidomide may potentially elicit unintended immune
      activity against allografts in solid organ transplant recipients. Here, we
      present a case of a renal transplant recipient who developed multiple myeloma
      after transplantation and was treated with the use of lenalidomide, which
      precipitated severe acute T-cell-mediated rejection. Lenalidomide was thought to
      be causative, and after cessation of the drug her renal function stabilized.

PMID- 29661457
TI  - Progressive Multifocal Leukoencephalopathy Following Combined Rituximab-Based
      Immune-Chemotherapy for Post-transplant Lymphoproliferative Disorder in a Renal
      Transplant Recipient: A Case Report.
AB  - BACKGROUND: Transplant recipients are at risk of developing progressive
      multifocal leukoencephalopathy (PML), an opportunistic infection due to
      reactivation of JC virus. Post-transplant lymphoproliferative disorders (PTLDs)
      represent a common malignancy in this population, and antiCD20-therapy has become
      an established component of its treatment. CASE PRESENTATION: We describe the
      first case of a renal allograft transplant recipient with PTLD who received
      rituximab-based immune-chemotherapy and developed PML shortly thereafter. Despite
      early suspicion and diagnosis, the disease ran a relentlessly progressive course,
      and the patient succumbed to his illness shortly thereafter. CONCLUSION: PML
      should be strongly suspected whenever unusual neurologic symptoms appear in the
      context of immunosuppression. Clinicians and patients should be aware of the
      potential for PML after rituximab therapy.

PMID- 29661459
TI  - Midpole Ureterocalycostomy for Renal Transplant Salvage: A Pediatric Case Report.
AB  - BACKGROUND: Ureteral obstruction is the most common urological complication of
      kidney transplantation. Obstruction secondary to ureteral stenosis can be an
      early or late complication. CASE REPORT: We present a patient in whom ureteral
      obstruction was initially identified at 2.5 months after transplant for which she
      underwent a midpole ureterocalycostomy between the midpole calyx of the
      transplant kidney and the native left ureter.

PMID- 29661458
TI  - Ombitasvir-Paritaprevir-Ritonavir Therapy in a Kidney Transplant Recipient With
      Chronic Hepatitis C Virus Genotype 1 Infection: A Case Report on the Importance
      of Considering Drug-Drug Interactions and Monitoring Cyclosporine Levels.
AB  - A 74-year-old Japanese man with a history of chronic hepatitis C and kidney
      transplant (KT) was administered pegylated-interferon plus ribavirin therapy.
      However, this therapy was ineffective. The patient was then hospitalized to
      receive ombitasvir (OBV) plus paritaprevir (PTV) plus ritonavir (r) antiviral
      combination therapy. He tested negative for the virus after 4 weeks, and
      completed 12 weeks of treatment. The patient ultimately achieved a sustained
      virological response after the 12 weeks of treatment. Cyclosporine (CyA) trough
      levels, during the OBV-PTV-r therapy, reached a peak within 5 days of initiating
      therapy, and increases in serum creatinine and total bilirubin were also
      observed. However, onset of irreversible nephropathy and hepatopathy were avoided
      by reducing the CyA dosage. The OBV-PTV-r therapy demonstrated a sufficient
      antiviral effect and could be safely administered postoperatively to patients
      having undergone KT. When a combination therapy with interferon-free, direct
      acting antivirals is used in patients post-transplantation, consideration of drug
      drug interactions with and monitoring CyA are of vital importance.

PMID- 29661460
TI  - Partial Cystectomy of Paraganglioma of the Urinary Bladder Before Living Kidney
      Transplantation: Case Report.
AB  - BACKGROUND: Paraganglioma (extra-adrenal pheochromocytoma) of the bladder is a
      very rare disease, accounting for 0.06% of all bladder tumors. Optimal management
      of bladder paraganglioma before kidney transplantation is unknown. We report a
      case of partial cystectomy for urinary bladder paraganglioma before living kidney
      transplantation. CASE PRESENTATION: A 59-year-old man with a 27-year history of
      hemodialysis was referred to our department for further examination of a bladder
      tumor detected during pre-transplantation testing. Cystoscopy revealed a
      submucosal tumor on the right side of the bladder. The patient experienced a
      hypertensive crisis during transurethral resection of the bladder tumor.
      Endocrinologic and pathologic examinations confirmed the diagnosis of
      paraganglioma in the urinary bladder. A partial cystectomy was performed before
      kidney transplantation. Nine months after partial cystectomy, the patient
      underwent AB0-incompatible living kidney transplantation from his spouse. No
      disease recurrence or graft rejection was observed 12 months after the
      transplantation. CONCLUSIONS: To our knowledge, this is the 1st report on the
      management of paraganglioma in the urinary bladder before living kidney
      transplantation. Kidney transplantation after partial cystectomy is an option
      that may be considered in patients with paraganglioma of the urinary bladder,
      with careful observations of bladder function and vesicoureteral reflux to the
      grafts.

PMID- 29661461
TI  - Urgent Living-Donor Liver Transplantation in a Patient With Concurrent Active
      Tuberculosis: A Case Report.
AB  - BACKGROUND: Although active tuberculosis (TB) is considered a contraindication
      for liver transplantation (LT), this is the only treatment in patients with liver
      failure and concurrent active TB. We report a case with successful urgent living
      donor LT for irreversible liver failure in the presence of active TB. CASE
      PRESENTATION: A 48-year-old man, with a history of decompensated alcoholic liver
      cirrhosis, was presented with stupor. At admission, his consciousness had
      deteriorated to semi-coma, and his renal function also rapidly deteriorated to
      hepatorenal syndrome. A preoperative computed tomography scan of the chest
      revealed several small cavitary lesions in both upper lobes, and acid-fast
      bacillus stain from his sputum was graded 2+. Adenosine deaminase levels from
      ascites were elevated, suggesting TB peritonitis. A first-line anti-TB drug
      regimen was started immediately (rifampin, isoniazid, levofloxacin, and
      amikacin). An urgent living-donor LT was performed 2 days later. After LT, the
      regimen was changed to second-line anti-TB drugs (amikacin, levofloxacin,
      cycloserine, and pyridoxine). The sputum acid-fast bacillus stain tested negative
      on postoperative day 10. His liver function remained well preserved, even after
      the reversion to first-line anti-TB treatment. The patient recovered without any
      anti-TB medication-related complications and was discharged. CONCLUSIONS: LT can
      be prudently performed as a life-saving option, particularly for patients with
      liver failure and concurrent active TB.

PMID- 29661462
TI  - Donor-Derived Candida dubliniensis Resulting in Perigraft Abscesses in a Liver
      Transplant Recipient Proven by Whole Genome Sequencing: A Case Report.
AB  - BACKGROUND: The transmission of fungi via transplant, although well-known, has
      not often been molecularly proven. We describe a case of donor-derived
      candidiasis verified by whole genome sequencing. CASE DESCRIPTION: The multiorgan
      donor was a 42-year-old woman with subdural hemorrhage. Procurement of the
      thoracic organs was performed followed by the abdominal organs. Tissue from the
      left bronchus grew Candida dubliniensis. The liver recipient was a 63-year-old
      woman with cryptogenic liver cirrhosis. She was noted to have worsening
      leukocytosis on postoperative day (POD) 9. Computed tomography of the abdomen and
      pelvis showed multiple rim-enhancing collections around the graft. Percutaneous
      drainage was performed. Fluid cultures grew C dubliniensis. C dubliniensis
      isolated from the donor's left bronchus and the liver recipient's abscesses were
      verified to be related by whole genome sequencing. We postulate that C
      dubliniensis colonizing the donor's transected trachea could have contaminated
      the inferior vena cava when the former was left open after explant of the donor's
      lungs. A portion of the donor's contaminated inferior vena cava was transplanted
      along with the liver graft, resulting in the infected collections in the
      recipient. CONCLUSIONS: Our case report highlights the importance of maintaining
      a sterile field during organ procurement, especially in a multiorgan donor whose
      organs are explanted in succession.

PMID- 29661463
TI  - Case Report of Multiple Bilobar Hepatic Arterio-Portal Fistulas Post-Liver
      Transplantation Managed Conservatively.
AB  - Multiple intrahepatic arterio-portal fistulas are rare. The majority are isolated
      and occur secondary to liver trauma including iatrogenic interventions such as
      liver biopsy. Post-liver transplantation 18 cases have been reported, all
      secondary to an interventional radiological procedure. We report multiple bi
      lobar arterio-portal fistulas in a liver transplant recipient recognized 1 year
      after transplantation. The donor died due to intracerebral bleeding following
      blunt head and abdominal trauma. In the present case, the etiology is not very
      clear. The patient was managed conservatively and to date has not required
      intervention.

PMID- 29661464
TI  - Cauliflower-like Neoplasm of Duodenal Papilla in a Liver Transplant Recipient:
      What Should We Think and Do? A Case Report.
AB  - BACKGROUND: With the continuous improvement of liver transplantation technology,
      the survival rate of liver transplantation has been improved, but recurrent or de
      novo malignancy remains one of the major factors affecting the long-term survival
      of liver transplant recipients. CASE REPORT: A 45-year-old Chinese man had a
      plastic biliary stent placed on account of biliary anastomotic stenosis after 3
      years of piggyback liver transplantation. He came to our hospital because of
      recurrent fever and jaundice for 2 weeks, and his carcinoembryonic antigen-199
      had increased. The patient's duodenal papillary was cauliflower-like at
      endoscopic retrograde cholangiopancreatography to replace the biliary stent. He
      was initially suspected of having duodenal papillary carcinoma after liver
      transplantation. However, the pathology from endoscopic retrograde
      cholangiopancreatography and endoscopic ultrasound-guided biopsy showed
      inflammation. While awaiting the result of biopsy, his CA-199 decreased
      significantly after anti-infection and symptomatic treatment. The patient was
      diagnosed with biliary anastomotic stenosis and duodenal papillitis. He was
      discharged uneventfully; to date, there is no evidence of malignant tumor.
      CONCLUSIONS: We report this case to provide helpful information to clinicians
      about the management of the duodenal papilla cauliflower-like neoplasm after
      liver transplantation, which should be considered as inflammatory first. Perhaps
      our view can avoid the risk of bringing an excessive medical treatment and
      unnecessary economic burden to patients and their families.

PMID- 29661465
TI  - Allograft Portacaval Shunt in Small-for-Size Liver in Deceased Donor Liver
      Transplant.
AB  - Portal hyperperfusion is detrimental to small-for-size livers (SFSLs) in liver
      transplantation. Surgical techniques modulating portal inflow provide the most
      effective approach to protect the SFSL. In this report, we describe a technique
      creating an allograft portacaval shunt that effectively attenuates portal inflow
      without a requirement of extensive surgical dissection in the recipient during
      the transplantation.

PMID- 29661466
TI  - Endobronchial Topical Amphotericin B Instillation for Pulmonary Chromomycosis
      After Lung Transplantation: A Case Report.
AB  - We report a very rare case of pulmonary chromomycosis caused by Scedosporium
      prolificans that developed after lung transplantation and was successfully
      treated with endobronchial topical amphotericin B instillation. The subject was a
      woman in her 50s with a history of bilateral lobar lung transplantation from
      living donors for idiopathic pulmonary hypertension. Eight years after the lung
      transplantation, chest radiography X-ray and computed tomography showed an
      abnormal shadow in the right lung. Bronchoscopic findings showed obstruction by a
      fungal component at the laterobasal bronchus B9. She was diagnosed with pulmonary
      chromomycosis after S. prolificans was detected in the bronchial aspirate.
      Systemic antifungal treatment with itraconazole was ineffective. Therefore, we
      administered topical amphotericin B weekly via endobronchial instillation and
      replaced oral itraconazole with voriconazole. The endobronchial procedure was
      safe and tolerable. Bronchial obstruction improved after three 3 instillations.
      We continued topical amphotericin B instillation once every 3 months for 2 years,
      and the abnormal shadow nearly disappeared. This case report describes infection
      by S. prolificans, which rarely becomes an etiologic agent in lung transplant
      patients, and shows that endobronchial topical amphotericin B instillation is a
      therapeutic option when systemic antifungal treatment is ineffective.

PMID- 29661467
TI  - Paradoxical Reaction of Tuberculosis in a Heart Transplant Recipient During
      Antituberculosis Therapy: A Case Report.
AB  - INTRODUCTION: Tuberculous paradoxical reactions (PRs) are excessive immune
      reactions occurring after antituberculosis (TB) treatment and are commonly
      observed in immunocompromised hosts such as patients infected with the human
      immunodeficiency virus. CASE REPORT: We recently encountered a 63-year-old male
      heart transplant recipient who developed tuberculous PR after treatment for
      miliary TB. The patient had been receiving immunosuppressive therapy with
      cyclosporine and mycophenolate mofetil for over 15 years. The diagnosis of
      miliary TB was made based on the presence of intermittent fever and fatigue;
      thus, anti-TB treatments (isoniazid, levofloxacin, ethambutol, and pyrazinamide)
      were started, which led to rapid defervescence and regression of the granular
      shadow and pleural effusion. However, a new persistent fever and confused state
      developed 1 month after the anti-TB therapy was started. After excluding possible
      etiologies of the patient's symptom, a PR was suspected, and anti-TB drugs were
      continued; corticosteroids were added as anti-inflammatory agents. After that, he
      has shown a favorable course with long-term anti-TB chemotherapy. CONCLUSION: A
      PR should always be considered when the patients' symptoms of tuberculosis re
      exacerbate after an appropriate anti-TB therapy. A PR commonly occurs in patients
      with various immunologic conditions including heart transplant recipients.

PMID- 29661468
TI  - Successful Treatment of Cytogenetically Normal Acute Myeloid Leukemia With Ten
      Eleven Translocation 2-Isocitrate Dehydrogenase 2 and Additional Sex Comb-like 1
      Nucleophosmin Co-mutations by HLA Haploidentical Stem Cell Transplantation: A
      Case Report and Literature Review.
AB  - The presence of recurrent gene mutations is increasingly important in acute
      myeloid leukemia (AML) and sheds new insights into the understanding of
      leukemogenesis, prognostic evaluation, and clinical therapeutic efficacy. Until
      now, ten-eleven translocation 2 (TET2) and isocitrate dehydrogenase 2 (IDH2)
      mutations were reported to be mutually exclusive in AML patients. Similarly,
      nucleophosmin (NPM1) and additional sex comb-like 1 (ASXL1) mutations were rarely
      coexisted in AML. A 47-year-old man diagnosed with high-risk AML presented
      simultaneous mutations of TET2-IDH2 and NPM1-ASXL1 revealed by next-generation
      sequencing. After successful treatment with chemotherapy followed by HLA
      haploidentical transplantation, he achieved a clinical complete remission without
      evidence of overt graft-versus-host disease. This case highlights that HLA
      haploidentical transplantation might be a safe and feasible therapy for AML
      patients who are characterized by TET2-IDH2 and NPM1-ASXL1 co-mutations.

PMID- 29661469
TI  - Successful 7-Year Eculizumab Treatment of Plasmapheresis-Resistant Recurrent
      Atypical Hemolytic-Uremic Syndrome due to Complement Factor H Hybrid Gene: A Case
      Report.
AB  - Atypical hemolytic-uremic syndrome (aHUS) is an extremely rare disease, and up to
      70% of the patients have a genetic mutation in the encoding components of
      complement activation or anti-complement factor H autoantibodies. The risk of
      recurrence after kidney transplantation is 10% to 80%. Eculizumab, a monoclonal
      antibody that binds complement protein C5, has shown to be highly effective in
      patients with aHUS; however, there are only few reports on the efficacy and
      safety of long-term eculizumab treatment in children with recurrent aHUS. Only 3
      case reports regard treatment in patients with complement factor H
      (CFH/CFHR1/CFHR3) hybrid gene. This report presents the efficacy and safety of
      long-term eculizumab treatment in a child with recurrent aHUS who has been
      successfully treated with eculizumab for more than 7 years. The patient presented
      as a 9-year-old with aHUS due to CFH/CFHR1/CFHR3 hybrid gene and received
      deceased donor kidney transplantation. After the transplantation, he experienced
      recurrence of aHUS 2 months later. Daily plasma exchanges were ineffective in the
      transplanted kidney; the patient became anuric and hemodialysis was needed.
      Eculizumab was started as therapy and led to complete remission of aHUS including
      restoration of diuresis. Eculizumab has been given as therapy for 7 years. The
      young patient is in a sustained remission without any adverse events. This
      patient is only the sixth patient reported with recurrent aHUS due to
      CFH/CFHR1/CFHR3 hybrid gene and is the patient with the longest remission of
      recurrent aHUS ever published.

PMID- 29661470
TI  - Special issue on simulation of traffic safety in the era of advances in
      technologies.

PMID- 29661471
TI  - Do the diagnostic criteria for subclinical hypercortisolism exist?
AB  - "Subclinical hypercortisolism" (SH) refers to a condition associated with a mild
      chronic increase in cortisol secretion. By definition, patients with SH do not
      exhibit specific symptoms of overt Cushing's syndrome (such as purple striae,
      easy bruising, proximal muscle weakness), SH has been preferred to "subclinical
      Cushing's syndrome", a semantic ambiguity since Cushing's syndrome is, by
      definition, a set of symptoms; and to the term "preclinical Cushing syndrome"
      because the progression toward overt clinical hypercortisolism is very rare.
      However, SH still is misnomer as a number of studies suggest that this condition
      may induce long-term non-specific adverse conditions related to the mild cortisol
      excess (i.e. diabetes, hypertension, obesity, and osteoporosis). Various attempts
      have been made to define SH that remains a matter of controversies and
      uncertainties.

PMID- 29661472
TI  - News about the genetics of congenital primary adrenal insufficiency.
AB  - Primary adrenal insufficiency (PAI) is characterized by impaired production of
      steroid hormones due to an adrenal cortex defect. This condition incurs a risk of
      acute insufficiency which may be life-threatening. Today, 80% of pediatric forms
      of PAI have a genetic origin but 5% have no clear genetic support. Recently
      discovered mutations in genes relating to oxidative stress have opened the way to
      research on genes unrelated to the adrenal gland. Identification of causal
      mutations in a gene responsible for PAI allows genetic counseling, guidance of
      follow-up and prevention of complications. This is particularly true for stress
      oxidative anomalies, as extra-adrenal manifestations may occur due to the
      sensitivity to oxidative stress of other organs such as the heart, thyroid,
      liver, kidney and pancreas.

PMID- 29661473
TI  - Silk fibroin preserves beta cell function under inflammatory stress while
      stimulating islet cell surface GLUT2 expression.
AB  - Silk fibroin is a novel biomaterial for enhancing transplanted islet cell
      function and survival. This study investigated whether silk fibroin may have
      unique properties that improve islet function in the face of inflammatory
      mediated stress during transplantation. Murine islet function was tested in vitro
      with either silk fibroin or alginate and challenged with inflammatory cytokines.
      The glucose-stimulated insulin secretion index for all conditions decreased with
      inflammatory cytokines, but was better preserved for islets exposed to silk
      compared to those exposed to alginate or medium. GLUT2 transporter expression on
      the cell surface of islets exposed to silk was increased compared to alginate or
      medium alone. Upon cytokine stress, a greater percentage of islet cells exposed
      to silk expressed GLUT2 on their surface. We conclude that preconditioning islets
      with silk fibroin stimulates islet cell surface GLUT2 expression, an increase,
      which persists under inflammatory stress, and may improve islet engraftment and
      function after transplantation.

PMID- 29661474
TI  - The role of hepatic macrophages in liver metastasis.
AB  - The liver is a major target organ for metastasis of both gastrointestinal and
      extra-gastrointestinal cancers. Due to its frequently inoperable nature, liver
      metastasis represents a leading cause of cancer-associated death worldwide. In
      the past years, the pivotal role of the immune system in this process is being
      increasingly recognised. In particular, the role of the hepatic macrophages, both
      recruited monocyte-derived macrophages (Mo-Mfs) and tissue-resident Kupffer cells
      (KCs), has been shown to be more versatile than initially imagined. However, the
      lack of tools to easily distinguish between these two macrophage populations has
      hampered the assignment of particular functionalities to specific hepatic
      macrophage subsets. In this Review, we highlight the most remarkable findings
      regarding the origin and functions of hepatic macrophage populations, and we
      provide a detailed description of their distinct roles in the different phases of
      the liver metastatic process.

PMID- 29661475
TI  - Usefulness of High-Dose Oral Flecainide for Termination of Recent-Onset Atrial
      Fibrillation in Children.
AB  - A high dose of oral flecainide has been used for acute termination of atrial
      fibrillation (AF) and atrial flutter or intra-atrial re-entry tachycardia (AFL
      IART) in adults. The use of flecainide for these conditions in children has not
      been well described. We describe our institutional experience on acute
      termination of AF or AFL-IART in children with a single high dose of oral
      flecainide in a hospital setting. All patients who received a single high dose of
      oral flecainide from 2009 to 2016 who were <21 years of age were included.
      Patients were treated only if AF or AFL-IART was less than 24 hours of duration.
      The dose was 300 mg for patients >70 kg, 200 mg for patients 40 to 70 kg, and 5
      mg/kg for patients <40 kg. Charts were reviewed to determine demographic
      information, flecainide dose, termination of arrhythmia, and time to termination.
      There were 22 patients identified. The median age was 16 years (range 4.6 to
      20.3) with a median weight of 75 kg (range 19 to 112). There were 13 patients
      with AF (11 with a normal heart, 85%) and 9 patients with AFL-IART (1 with a
      normal heart, 11%) (p <0.05). The median dose of flecainide given was 3.6 mg/kg
      (range 2.7 to 6.1) or 136 mg/m2 (range 90 to 171). AF in all patients (13/13,
      100%) and AFL-IART in 5 of 9 patients (55%) terminated acutely (p <0.05). All
      patients with normal heart (12/12, 100%) and 6 of the 10 patients (60%) with
      heart disease have their arrhythmia terminated acutely (p <0.05). The only
      patients whose tachycardia did not terminate were 4 patients with IART and heart
      disease. The arrhythmia terminated in a median time of 60 minutes (range 30 to
      120). There were no adverse events or proarrhythmia encountered. In conclusion, a
      single high dose of oral flecainide successfully terminated AF of less than 24
      hours' duration in all pediatric patients without side effects. This approach is
      less effective for AFL-IART in patients with heart disease.

PMID- 29661476
TI  - Cutaneous presentation of adult T-cell leukemia/lymphoma (ATLL). Single-center
      study on 37 patients in metropolitan France between 1996 and 2016.
AB  - INTRODUCTION: Adult T-cell leukemia/lymphoma (ATLL) is a hematological malignancy
      associated with chronic HTLV-1 infection. AIM: To describe skin lesions in ATLL.
      METHODS: A descriptive, retrospective study between 1996 and 2016, including all
      patients diagnosed with ATLL at Saint-Louis Hospital (Paris, France). RESULTS:
      Thirty-seven ATLL patients were included. Fifteen patients (41%) had a cutaneous
      localization of the disease, which was present from the beginning of the disease
      for two thirds of them. ATLL types in patients with cutaneous localization of the
      disease were as follows: lymphoma, n=5, chronic, n=4, smoldering, n=4, acute,
      n=2. Half the patients had 2 or more cutaneous manifestations. The cutaneous
      localizations observed were as follows: nodulotumoral (n=8), plaques (n=7),
      multipapular (n=6), macular (n=4), purpuric (n=2). Among the 15 patients with
      cutaneous localization, median overall survival was significantly shorter in the
      acute and lymphoma types compared to the smoldering and chronic types (8.7 months
      vs. 79 months, P=0.003). DISCUSSION: ATLL is a hematologic malignancy with
      variable expression that is diagnosed only very rarely in metropolitan France,
      but that should be sought in patients from countries with high HTLV-1 prevalence
      in the event of a chronic eruption with patches, papules, plaques and/or tumors.
      The chronic and smoldering types are relatively indolent, whereas the acute and
      lymphoma forms have a poor prognosis.

PMID- 29661477
TI  - Low diastolic blood pressure and adverse outcomes in heart failure with preserved
      ejection fraction.
AB  - BACKGROUND: It remains unknown whether a low diastolic blood pressure (DBP)
      increases the risks of cardiovascular events and death in patients with heart
      failure with preserved ejection fraction (HFpEF). METHODS: We used data from the
      TOPCAT trial. The primary outcome was a composite of all-cause death, non-fatal
      myocardial infarction, non-fatal stroke, or hospitalization for heart failure.
      Hazard ratios (HRs) were analyzed for DBPs of <60, 60-69, 70-79, and >=90 mm Hg
      in comparison with a DBP of 80-89 mm Hg using multivariable Cox proportional
      hazard models. RESULTS: This study included 3417 patients with HFpEF who had a
      controlled blood pressure. In the mean follow-up period of 3.0 years, 881
      patients experienced at least one confirmed primary outcome event. Compared with
      patients with a DBP of 80-89 mm Hg, the adjusted HRs for primary outcome events
      were significantly higher in those with DBPs of <60 mm Hg (HR: 2.19 [95%
      confidence interval,1.72-2.78]) and 60-69 mm Hg (HR: 1.52 [1.23-1.87]).
      Similarly, the adjusted HRs for all-cause death, major cardiovascular events, and
      hospitalization for heart failure, but not stroke, were significantly higher in
      patients with a DBP of <70 mm Hg. A relationship between a low DBP and adverse
      outcomes was found in HFpEF patients with a systolic blood pressure of >=120 mm
      Hg; however, a low systolic blood pressure with a DBP of >=70 mm Hg was not
      associated with these event risks. CONCLUSIONS: A low DBP increased the risks of
      adverse outcomes in patients with HFpEF.

PMID- 29661478
TI  - Chronic adriamycin treatment impairs CGRP-mediated functions of meningeal sensory
      nerves.
AB  - Adriamycin is a potent anthracycline-type antitumor agent, but it also exerts
      potentially serious side effects due to its cardiotoxic and neurotoxic
      propensity. Multiple impairments in sensory nerve functions have been recently
      reported in various rat models. The present experiments were initiated in an
      attempt to reveal adriamycin-induced changes in sensory effector functions of
      chemosensitive meningeal afferents. Meningeal blood flow was measured with laser
      Doppler flowmetry in the parietal dura mater of adult male Wistar rats. The dura
      mater was repeatedly stimulated by topical applications of capsaicin, a transient
      receptor potential vanilloid 1 (TRPV1) receptor agonist, or acrolein, a transient
      receptor potential ankyrin 1 (TRPA1) receptor agonist, which induce the release
      of calcitonin gene-related peptide (CGRP) from meningeal afferents. The blood
      flow increasing effects of CGRP, histamine, acetylcholine and forskolin were also
      measured. Capsaicin- and acrolein-induced CGRP release was measured with enzyme
      linked immunoassay in an ex vivo dura mater preparation. TRPV1 content of
      trigeminal ganglia and TRPV1-, CGRP- and CGRP receptor component-immunoreactive
      structures were examined in dura mater samples obtained from control and
      adriamycin-treated rats. The vasodilator effects of capsaicin, acrolein and CGRP
      were significantly reduced in adriamycin-treated animals while histamine-,
      acetylcholine- and forskolin-induced vasodilatation were unaffected. Measurements
      of CGRP release in an ex vivo dura mater preparation revealed an altered dynamic
      upon repeated stimulations of TRPV1 and TRPA1 receptors. In whole-mount dura
      mater preparations immunohistochemistry revealed altered CGRP receptor component
      protein (RCP)-immunoreactivity in adriamycin-treated animals, while CGRP receptor
      activity modifying protein (RAMP1)-, TRPV1- and CGRP-immunostaining were left
      apparently unaltered. Adriamycin-treatment slightly reduced TRPV1 protein content
      of trigeminal ganglia. The present findings demonstrate that adriamycin-treatment
      alters the function of the trigeminovascular system leading to reduced meningeal
      sensory neurogenic vasodilatation that may affect the local regulatory and
      protective mechanisms of chemosensitive afferents leading to alterations in
      tissue integrity.

PMID- 29661479
TI  - The Minimally Conscious State, the Disability Bias, and the Moral Authority of
      Advance Directives.

PMID- 29661480
TI  - Monitoring country progress and achievements by making global predictions: is the
      tail wagging the dog?

PMID- 29661481
TI  - Response to 'The use of laryngeal mask airway for adenoidectomy'.

PMID- 29661482
TI  - Anisotropy and Spatial Heterogeneity in Quantitative Ultrasound Parameters:
      Relevance to the Study of the Human Cervix.
AB  - Imaging biomarkers based on quantitative ultrasound can offer valuable
      information about properties that inform tissue function and behavior such as
      microstructural organization (e.g., collagen alignment) and viscoelasticity
      (i.e., compliance). For example, the cervix feels softer as its microstructure
      remodels during pregnancy, an increase in compliance that can be objectively
      quantified with shear wave speed and therefore shear wave speed estimation is a
      potential biomarker of cervical remodeling. Other proposed biomarkers include
      parameters derived from the backscattered echo signal, such as attenuation and
      backscattered power loss, because such parameters can provide insight into tissue
      microstructural alignment and organization. Of these, attenuation values for the
      pregnant cervix have been reported, but large estimate variance reduces their
      clinical value. That said, parameter estimates based on the backscattered echo
      signal may be incorrect if assumptions they rely on, such as tissue isotropy and
      homogeneity, are violated. For that reason, we explored backscatter and
      attenuation parameters as potential biomarkers of cervical remodeling via careful
      investigation of the assumptions of isotropy and homogeneity in cervical tissue.
      Specifically, we estimated the angle- and spatial-dependence of parameters of
      backscattered power and acoustic attenuation in the ex vivo human cervix, using
      the reference phantom method and electronic steering of the ultrasound beam. We
      found that estimates are anisotropic and spatially heterogeneous, presumably
      because the tissue itself is anisotropic and heterogeneous. We conclude that
      appropriate interpretation of imaging biomarkers of cervical remodeling must
      account for tissue anisotropy and heterogeneity.

PMID- 29661483
TI  - Quantitative Measurement of Erythrocyte Aggregation as a Systemic Inflammatory
      Marker by Ultrasound Imaging: A Systematic Review.
AB  - This systematic review is aimed at answering two questions: (i) Is erythrocyte
      aggregation a useful biomarker in assessing systemic inflammation? (ii) Does
      quantitative ultrasound imaging provide the non-invasive option to measure
      erythrocyte aggregation in real time? The search was executed through
      bibliographic electronic databases CINAHL, EMB Review, EMBASE, MEDLINE, PubMed
      and the grey literature. The majority of studies correlated elevated erythrocyte
      aggregation with inflammatory blood markers for several pathologic states. Some
      studies used "erythrocyte aggregation" as an established marker of systemic
      inflammation. There were limited but promising articles regarding the use of
      quantitative ultrasound spectroscopy to monitor erythrocyte aggregation.
      Similarly, there were limited studies that used other ultrasound techniques to
      measure systemic inflammation. The quantitative measurement of erythrocyte
      aggregation has the potential to be a routine clinical marker of inflammation as
      it can reflect the cumulative inflammatory dynamics in vivo, is relatively simple
      to measure, is cost-effective and has a rapid turnaround time. Technologies like
      quantitative ultrasound spectroscopy that can measure erythrocyte aggregation non
      invasively and in real time may offer the advantage of continuous monitoring of
      the inflammation state and, thus, may help in rapid decision making in a critical
      care setup.

PMID- 29661484
TI  - The Cell Cycle Progression Score: Unclear Role in Renal Cell Carcinoma.

PMID- 29661485
TI  - Re: Karim A. Touijer, Robert Jeffery Karnes, Niccolo Passoni, et al. Survival
      Outcomes of Men with Lymph Node-positive Prostate Cancer After Radical
      Prostatectomy: A Comparative Analysis of Different Postoperative Management
      Strategies. Eur Urol 2018;73:890-6.

PMID- 29661486
TI  - Pre-encoding stress induced changes in perceived stress, blood pressure and
      cortisol are differentially associated with recollection and familiarity.
AB  - Stress before encoding is often linked to impaired memory. Further influences of
      stress on memory are arousal of the to be learned material and memory retrieval
      type (free recall vs. recognition). In the current study we tested the influence
      of stress on memory encoding for neutral and negative arousing pictures in
      healthy young adults. A total of 80 participants (40 men) were subjected either
      to the socially evaluated cold pressure test or a control condition before
      encoding of arousing and neutral pictures. One day later participants underwent a
      recognition test. Results show different relationships between the obtained
      stress markers and recognition memory. Higher perceived stress ratings predicted
      poorer overall accuracy for arousing material. Lower perceived stress ratings and
      larger blood pressure increase predicted higher recollection values for arousing
      material. In contrast, a larger cortisol increase predicted lower familiarity
      values for arousing material. Concluding, activity of the sympathetic nervous
      system (SNS) and a lower feeling of perceived stress predict better recollection.
      HPA axis activity predicts lower familiarity. Pre-encoding induced changes in the
      perceived feeling of stress, activity of the SNS, and activity of the HPA axis
      show specific and distinct relationships to recognition memory.

PMID- 29661487
TI  - RIPK1 downregulation in keratinocyte enhances TRAIL signaling in psoriasis.
AB  - BACKGROUND: Psoriasis, a common inflammatory skin disorder characterized by scaly
      erythema and plaques, is induced by dysregulation of dendritic cell- and T cell
      mediated immune reaction. Receptor-interacting protein kinase 1 (RIPK1) regulates
      inflammatory signaling in response to stimuli such as TNF-alpha, TRAIL, and TLRs,
      resulting in apoptosis, necroptosis and NF-kappaB activation. However, the
      physiological relevance in human epidermis remains elusive. OBJECTIVE: In this
      study, we examined whether RIPK1 is involved in the pathogenesis of psoriasis
      vulgaris. METHODS: Skin samples of eight patients with psoriasis vulgaris were
      investigated by western blotting and immunohistochemistry. The functions of RIPK1
      in keratinocytes were examined by RT-PCR and ELISA in vitro. TRAIL-neutralization
      experiment was employed in an imiquimod-induced murine psoriasis model. RESULTS:
      In lesional psoriatic epidermis, RIPK1-expression was decreased compared with
      that in normal epidermis. Cytokines involved in the pathomechanism of psoriasis,
      such as IL-1beta, IL-17A, IL-22 and TRAIL, reduced RIPK1-expression in normal
      human epidermal keratinocytes (HEK) in vitro. In addition, RIPK1-knockdown
      enhanced TRAIL-mediated expression of psoriasis-relating cytokines, such as IL
      1beta, IL-6, IL-8, TNF-alpha, in HEK. Numerous TRAIL-positive cells were detected
      in the dermis of lesional psoriatic skin, and TRAIL receptors were expressed in
      psoriatic epidermis and HEK in conventional cultures. Moreover, TRAIL
      neutralization in an imiquimod-induced murine psoriasis model remarkably improved
      skin phenotypes, such as ear thickness, and TNF-alpha expression in lesional
      skin. CONCLUSIONS: These results lead us to conclude that RIPK1-downregulation in
      keratinocytes increases their susceptibility to TRAIL stimulation, and plays a
      role in the pathogenesis of psoriasis vulgaris.

PMID- 29661488
TI  - Psychometric evaluation of the WHOQOL-BREF, Taiwan version, across five kinds of
      Taiwanese cancer survivors: Rasch analysis and confirmatory factor analysis.
AB  - BACKGROUND: Quality of life (QoL) is important for clinicians to evaluate how
      cancer survivors judge their sense of well-being, and WHOQOL-BREF may be a good
      tool for clinical use. However, at least three issues remain unresolved: (1) the
      psychometric properties of the WHOQOL-BREF for cancer patients are insufficient;
      (2) the scoring method used for WHOQOL-BREF needs to be clarify; (3) whether
      different types of cancer patients interpret the WHOQOL-BREF similarly. METHODS:
      We recruited 1000 outpatients with head/neck cancer, 1000 with colorectal cancer,
      965 with liver cancer, 1438 with lung cancer and 1299 with gynecologic cancers in
      a medical center. Data analyses included Rasch models, confirmatory factor
      analysis (CFA), and Pearson correlations. RESULTS: The mean WHOQOL-BREF domain
      scores were between 13.34 and 14.77 among all participants. CFA supported
      construct validity; Rasch models revealed that almost all items were embedded in
      their expected domains and were interpreted similarly across five types of cancer
      patients; all correlation coefficients between Rasch scores and original domain
      scores were above 0.9. CONCLUSIONS: The linear relationship between Rasch scores
      and domain scores suggested that the current calculations for domain scores were
      applicable and without serious bias. Clinical practitioners may regularly collect
      and record the WHOQOL-BREF domain scores into electronic health records.

PMID- 29661489
TI  - Comparison of the effects of edoxaban, an oral direct factor Xa inhibitor, on
      venous thromboembolism between patients with and without cancer.
AB  - BACKGROUND: Venous thromboembolism (VTE) is a frequent and serious complication
      of cancer. The current guidelines in the USA and Europe recommend low-molecular
      weight heparin (LMWH) for the treatment of cancer-associated VTE. In Japan, LMWH
      is not given for the treatment of VTE; instead edoxaban, an oral direct factor Xa
      inhibitor, was approved for the treatment of VTE in September 2014. However, the
      efficacy and safety of the factor Xa inhibitor in cancer patients have not been
      fully elucidated. METHODS: Patients' charts were reviewed retrospectively, and
      125 VTE patients (61 cancer patients) in whom edoxaban therapy was started
      between September 2014 and September 2016 were included in this study. Patients'
      demographics, changes in VTE amount, VTE recurrence, clinically relevant
      bleeding, and outcomes until February 2017 were examined. RESULTS: Patients'
      characteristics, including age, sex, weight, creatinine clearance, and duration
      of administration of edoxaban were comparable between cancer and non-cancer
      patients. No parenteral anticoagulant pretreatment before edoxaban was given in
      37.5% and 55.7% of non-cancer and cancer patients, respectively. The incidence of
      pulmonary embolism was also similar in the two groups. The amount of thrombosis
      decreased ("improved") or disappeared ("normalized") in 89.6% and 94.1%,
      respectively, of non-cancer and cancer patients who underwent at least two
      imaging tests. The frequencies of recurrence of VTE and clinically relevant
      bleeding were not significantly different between the two groups (p=0.414 and
      0.516, respectively). However, 21 cancer patients died, 17 of whom died of
      cancer, while none of the non-cancer patients died. CONCLUSION: The present study
      showed that the efficacy and safety of edoxaban for the treatment of VTE is
      comparable between cancer and non-cancer patients. Edoxaban may be a clinically
      useful therapy for VTE in Japanese cancer patients.

PMID- 29661490
TI  - Amygdala volume mediates the relationship between externalizing symptoms and
      daily smoking in adolescence: A prospective study.
AB  - The current study examined amygdala and orbitofrontal cortex (OFC) volumes as
      mediators of the relationship between externalizing symptoms and daily smoking in
      adolescence. Externalizing behaviors are among the most robust predictors of
      adolescent smoking, and there is emerging evidence that volume reductions in the
      amygdala and OFC are associated with risk for substance misuse as well as
      aggressive, impulsive, and disinhibited tendencies. Using a prospective
      longitudinal design, we recruited 109 adolescents who provided data on brain
      volume and externalizing behaviors at age 12, and on smoking at age 18. Daily
      smoking at age 18 (n = 27) was predicted by externalizing behaviors (measured by
      the self-report Child Behavior Checklist, CBCL) as well as smaller right amygdala
      volumes. Right amygdala volumes mediated the relationship between externalizing
      symptoms and later smoking. These findings provide important insight into the
      neurobiological risk factors associated with adolescent smoking, and, more
      generally, into factors that may be associated with vulnerability to substance
      use disorders and related psychopathology.

PMID- 29661491
TI  - When to SAVR in the age of TAVR? A perspective on surgical aortic valve
      replacement in 2018.

PMID- 29661492
TI  - Wrist or Groin? Learning From the Wisdom of the Crowd.

PMID- 29661493
TI  - Neuroimaging Findings in Normocephalic Zika Virus Infection.

PMID- 29661494
TI  - Response to the Letter by Sora Yasri.

PMID- 29661495
TI  - Narcotics reduction, quality and safety in gynecologic oncology surgery in the
      first year of enhanced recovery after surgery protocol implementation.
AB  - OBJECTIVES: Enhanced Recovery After Surgery (ERAS) programs are mechanisms for
      achieving value-based improvements in surgery. This report provides a detailed
      analysis of the impact of an ERAS program on patient outcomes as well as quality
      and safety measures during implementation on a gynecologic oncology service at a
      major academic medical center. METHODS: A retrospective review of gynecologic
      oncology patients undergoing elective laparotomy during the implementation phase
      of an ERAS program (January 2016 through December 2016) was performed. Patient
      demographics, surgical variables, postoperative outcomes, and adherence to core
      safety measures, including antimicrobial and venous thromboembolism (VTE)
      prophylaxis, were compared to a historical patient cohort (January 2015 through
      December 2015). Statistical analyses were performed using t-tests, Wilcoxon rank
      sum tests, and Chi squared tests. RESULTS: The inaugural 109 ERAS program
      participants were compared to a historical patient cohort (n=158). There was no
      difference in BMI, race, malignancy, or complexity of procedure between cohorts.
      ERAS patients required less narcotics (70.7 vs 127.4, p=0.007, oral morphine
      equivalents) and PCA use (32.1% vs. 50.6%, p=0.002). Despite this substantial
      reduction in narcotics, ERAS patients did not report more pain and in fact
      reported significantly less pain by postoperative day 3. There were no
      differences in length of stay (5days), complication rates (13.8% vs. 20.3%,
      p=0.17) or 30-day readmission rates (9.5 vs 11.9%, p=0.54) between ERAS and
      historical patients, respectively. Compliance with antimicrobial prophylaxis was
      97.2%. However, 33.9% of ERAS patients received substandard preoperative VTE
      prophylaxis. CONCLUSIONS: ERAS program implementation resulted in reductions in
      narcotic requirements and PCA use without changes in length of stay or
      readmission rates. Compliance should be diligently audited during the
      implementation phase of ERAS programs, with special attention to adherence to pre
      existing core safety measures.

PMID- 29661496
TI  - Abuse, cancer and sexual dysfunction in women: A potentially vicious cycle.
AB  - More than 30% of women have a history of abuse. Women with cancer may be at
      substantially increased risk for abuse, but this issue is rarely discussed in the
      course of oncology care. Women with a history of abuse who present for cancer
      care commonly have a high prevalence of co-morbid illness. Sexual dysfunction, a
      highly prevalent but under-recognized condition among women of all ages, is also
      more common among both women with a history of abuse and women with cancer.
      Although common after cancer, sexual dysfunction, like abuse, can be stigmatizing
      and often goes undiagnosed and untreated. This review first examines the
      literature for evidence of a relationship between any history of abuse and cancer
      among women, addressing two questions: 1) How does abuse promote or create risk
      for developing cancer? 2) How does cancer increase a woman's susceptibility to
      abuse? We then examine evidence for a relationship between abuse and female
      sexual dysfunction, followed by an investigation of the complex relationship
      between all three factors: abuse, sexual dysfunction and cancer. The literature
      is limited by a lack of harmonization of measures across studies, retrospective
      designs, and small and idiosyncratic samples. Despite these limitations, it is
      imperative that providers integrate the knowledge of this complex relationship
      into the care of women with cancer.

PMID- 29661497
TI  - Postoperative chemotherapy for node-positive cervical cancer: Results of a
      multicenter phase II trial (JGOG1067).
AB  - OBJECTIVE: This multicenter phase II Japanese Gynecologic Oncology Group study
      (JGOG1067) was designed to evaluate the efficacy and safety of postoperative
      chemotherapy in patients with node-positive cervical cancer. METHODS: Patients
      with stage IB-IIA squamous cervical cancer who underwent radical hysterectomy and
      were confirmed to have pelvic lymph node metastasis were eligible for this study.
      The patients postoperatively received irinotecan (CPT-11; 60mg/m2 intravenously
      on days 1 and 8) and nedaplatin (NDP; 80mg/m2 intravenously on day 1).
      Chemotherapy administration commenced within 6weeks after surgery and was
      repeated every 28days for up to 5cycles. The primary endpoint of this study was
      the 2-year recurrence-free survival (RFS) rate. The secondary endpoints were the
      5-year overall survival (OS) rate, 5-year RFS rate, and adverse events such as
      complications of chemotherapy and lower-limb edema. RESULTS: Sixty-two patients
      were analyzed according to our protocol, among whom 55 (88.7%) completed 5cycles
      of scheduled treatment. The median follow-up period was 66.1months (range, 16.8
      96.6months). The 2-year and 5-year RFS rates were 87.1% (95% confidence interval
      [CI]: 75.9-99.3) and 77.2% (95% CI: 64.5-85.8), respectively. Fourteen patients
      (22.5%) experienced recurrence during the follow-up period, 8 of whom died of the
      disease. The 5-year OS rate in this study was 86.5% (95% CI: 74.8-93.0). Only
      9.7% of the patients experienced lymphedema in their legs. CONCLUSION:
      Postoperative chemotherapy without radiotherapy was found to be very effective in
      high-risk patients with node-positive cervical cancer.

PMID- 29661498
TI  - The intra-day dynamics of affect, self-esteem, tiredness, and suicidality in
      Major Depression.
AB  - Despite growing interest in the temporal dynamics of Major Depressive Disorder
      (MDD), we know little about the intra-day fluctuations of key symptom constructs.
      In a study of momentary experience, the Experience Sampling Method captured the
      within-day dynamics of negative affect, positive affect, self-esteem, passive
      suicidality, and tiredness across clinical MDD (N= 31) and healthy control groups
      (N= 33). Ten symptom measures were taken per day over 6 days (N= 2231
      observations). Daily dynamics were modeled via intra-day time-trends,
      variability, and instability in symptoms. MDD participants showed significantly
      increased variability and instability in negative affect, positive affect, self
      esteem, and suicidality. Significantly different time-trends were found in
      positive affect (increased diurnal variation and an inverted U-shaped pattern in
      MDD, compared to a positive linear trend in controls) and tiredness (decreased
      diurnal variation in MDD). In the MDD group only, passive suicidality displayed a
      negative linear trend and self-esteem displayed a quadratic inverted U trend. MDD
      and control participants thus showed distinct dynamic profiles in all symptoms
      measured. As well as the overall severity of symptoms, intra-day dynamics appear
      to define the experience of MDD symptoms.

PMID- 29661499
TI  - The relationship between complement levels and disease activity in Japanese
      family cases of hereditary angioedema with C1-INH deficiency.

PMID- 29661500
TI  - Severity of eczema and mental health problems in Japanese schoolchildren: The
      ToMMo Child Health Study.
AB  - BACKGROUND: The association between eczema and mental health problems in
      schoolchildren has been underexplored. We aimed to investigate this association
      with the validated questionnaires. METHODS: Of 46,648 invited children, we
      analyzed 9954 (21.3%) in the 2nd to the 8th grades from the ToMMo Child Health
      Study conducted in 2014 and 2015, a cross-sectional survey in Miyagi Prefecture,
      Japan. We defined eczema status as "normal," "mild/moderate," or "severe," based
      on the presence of persistent flexural eczema and sleep disturbance, according to
      the International Study of Asthma and Allergies in Childhood (ISAAC) Eczema
      Symptom Questionnaire. Clinical ranges of Strengths and Difficulties
      Questionnaire (SDQ) total difficulties scores and four SDQ subcategories of
      emotional symptoms, conduct problems, hyperactivity/inattention, and peer
      problems were defined as scores >=16, >=5, >=5, >=7, and >=5, respectively.
      RESULTS: The mean SDQ total difficulties score significantly increased as eczema
      status worsened (all P <= 0.004 for trend). The OR of scores in the clinical
      range for SDQ total difficulties were 1.51 (95% CI, 1.31-1.74) for mild/moderate
      eczema and 2.63 (95% CI, 1.91-3.63) for severe eczema (P < 0.001 for trend),
      adjusted for sex, school grade, current wheeze, and disaster-related factors,
      using normal eczema as a reference. The association between severity of eczema
      and four SDQ subcategories showed a similar trend (all P <= 0.017 for trend).
      CONCLUSIONS: We found a significant association between severity of eczema and
      mental health problems. The presence of eczema was associated with four SDQ
      subcategories.

PMID- 29661501
TI  - Mechanical strain induced phospho-proteomic signaling in uterine smooth muscle
      cells.
AB  - Mechanical strain associated with the expanding uterus correlates with increased
      preterm birth rates. Mechanical signals result in a cascading network of protein
      phosphorylation events. These signals direct cellular activities and may lead to
      changes in contractile phenotype and calcium signaling. In this study, the
      complete phospho-proteome of uterine smooth muscle cells subjected to mechanical
      strain for 5 min was compared to un-strained controls. Statistically significant,
      differential phosphorylation events were annotated by Ingenuity Pathway Analysis
      to elucidate mechanically induced phosphorylation networks. Mechanical strain
      leads to the direct activation of ERK1/2, HSPB1, and MYL9, in addition to
      phosphorylation of PAK2, vimentin, DOCK1, PPP1R12A, and PTPN11 at previously
      unannotated sites. These results suggest a novel network reaction to mechanical
      strain and reveal proteins that participate in the activation of contractile
      mechanisms leading to preterm labor.

PMID- 29661502
TI  - Unusual occurrence reporting system: Sharing a ten years experience from a
      tertiary care JCIA accredited university hospital.
AB  - PURPOSE: Identifying a true measure of safety is challenging in radiation
      oncology. A culture of unusual reporting may however be used as an indirect
      measure for it. The purpose of this study is to share our experience of unusual
      occurrence reporting system, established in the Radiation Oncology section since
      2006, the first of this nature in Pakistan. MATERIALS AND METHODS: Data is
      collected over the last ten years. An in-house online reporting system has been
      developed for reporting unusual events. All the reported events are evaluated
      retrospectively. The stage of unusual occurrence along the radiation therapy
      process, possible causes, severity and preventive measures taken are discussed.
      RESULTS: Analysis of the 501 unusual occurrences reported over the last ten years
      has shown a substantial decrease in the number of significant mistakes observed.
      Of the total, 57 % unusual occurrences have been reported by radiation therapy
      technologists, including treatment preparation processes. Oversight is supposed
      to be the most common cause for unusual occurrences. CONCLUSIONS: The ten years
      experience with reporting and documenting of unusual occurrences resulted in a
      safety culture where every individual is willing to share any type of incident
      with a free well. Our experience at the Aga Khan University Hospital (AKUH) shows
      that the major reason for the occurrence of incidents was oversight. The majority
      of unusual occurrences were reported by radiation therapy technologists, as
      expected, since they handle the bulk of the treatment planning process.

PMID- 29661503
TI  - Treatment in Fabry disease.
AB  - Fabry disease is an X-linked inborn disease caused by deficit of alpha
      galactosidaseA. This results in accumulation of glycosphingolipids in all cells
      and tissues. All males should receive enzyme replacement treatment in case of
      very low or undetectable levels of alpha-galactosidaseA. Female carriers and
      males with marginally levels of alpha-galactosidaseA should be treated in case of
      renal, neurologic o cardiac manifestations. There are two intravenous
      formulations of human recombinant enzyme, agalsidase alpha and agalsidase beta,
      showing similar efficacy and safety. Patients with amenable mutations of alpha
      galactosidase can be treated with oral migalastat hydrochloride. Migalastat
      hydrochloride is a pharmacological chaperone that facilitates trafficking of
      alpha-galactosidaseA to lysosomes increasing enzyme activity. Patients treated
      with migalastat hydrochloride had significant improvements in left ventricular
      mass and gastrointestinal symptoms.

PMID- 29661504
TI  - Stress-induced hyperglycemia on complications in non-critically elderly
      hospitalized patients.
AB  - AIMS: Hospital complications and hyperglycemia are common in elderly patients
      during hospitalization. Our aim was to analyze the relationship between
      hyperglycemia and hospital complications in an ageing population. METHODS: We
      conducted an observational study to evaluate the association between maximum
      blood glucose (MBG) levels and hospital complications. Patients were stratified
      according to the quartiles of MBG levels. Diabetes mellitus (DM) was determined
      by patient history and/or admission glycated hemoglobin (HbA1c) level >=6.5%.
      Hyperglycemia in patients without DM was defined as stress-induced hyperglycemia
      (SH). The composite primary end-point included frequent complications and/or all
      cause hospital mortality. RESULTS: Among 461 patients, mean age 80+/-7.5years,
      238 (51.6%) patients had DM, 20 had undiagnosed DM, and 162 (35.1%) developed
      hospital complications. Patients with complications had higher mean daily BG
      levels (215+/-84 vs 195+/-85mg/dl, P<.01). The incidence of complications was
      directly associated with severity of hyperglycemia according to the quartiles of
      MBG levels in patients without DM, namely SH (<140 mg/dl, 22.2%; 140-185mg/dl,
      40%; 186-250mg/dl, 47%; >250mg/dl, 60%; P=.002), but not in patients with DM
      (<140mg/dl, 26.3%; 140-185mg/dl, 40.4%; 186-250mg/dl, 35.6%; >250mg/dl, 37.4%;
      P=.748). In the multivariate analyses, SH was independently associated with
      complications: OR 2.60 (CI95%: 1.2-5.6), 2.82 (CI95%: 1.2-6.5), 5.50 (CI95%: 1.4
      20.8) for the second, third and fourth quartile respectively (P=.01), as compared
      to the first quartile. We found no association with readmissions and all-cause
      mortality. CONCLUSIONS: SH in elderly patients is associated with hospital
      complications, but not with all-cause mortality, compared to patients with
      diabetes or normoglycemia.

PMID- 29661506
TI  - Quality of life seems to be independent of severity of pretransplant illness in
      lung transplant recipients.

PMID- 29661505
TI  - Training cardiothoracic surgeons of the future: The UK experience.
AB  - OBJECTIVE: The study aimed to assess targeted simulation courses, including live
      animal operating, as complementary training tools with regard to 2 key surgical
      skills in early cardiothoracic surgeon training. METHODS: Twenty UK surgical
      trainees (equivalent to cardiothoracic surgery resident physicians in the United
      States) in their first year of residency training were evaluated. Assessment of
      skills in pulmonary wedge resection and cardiopulmonary bypass were undertaken
      before and after 2 boot camp-style courses, including live animal operating (boot
      camp 1 and boot camp 2). Resident performance was evaluated by surgical trainers
      using objective structured assessment of technical skills matrices. Trainers
      completed a survey on skill development and trainer confidence in the trainee
      precourse and postcourse. RESULTS: Trainee assessment scores pre- and postcourses
      were analyzed using a 2-tailed Wilcoxon signed-rank test demonstrating a
      significant improvement in trainee performance in boot camp 1 in performing
      cardiopulmonary bypass (median score, 21 precourse and 28 postcourse; P = .001)
      and pulmonary wedge resection (median score, 25 precourse and 32 postcourse; P =
      .012), and in boot camp 2, in performing cardiopulmonary bypass (median score, 28
      precourse and 30.5 postcourse; P = .018) and pulmonary wedge resection (median
      score, 31.5 precourse and 37 postcourse; P = .018). Trainers reported increased
      confidence and decision-making competency of residents and increased confidence
      of trainers to allow more participation in management. It was found that 83.3% of
      trainers would support trainee attendance in subsequent years. CONCLUSIONS: Live
      animal operating as a component of targeted cardiothoracic surgery skill training
      courses significantly improves technical skills, builds confidence of surgical
      trainers in resident physicians' practice, and should be supported by the surgery
      community.

PMID- 29661507
TI  - Discussion.

PMID- 29661508
TI  - Variability in the multicentre National Registry in Active Surveillance; a
      questionnaire for urologists.
AB  - BACKGROUND: Our main objective was to report the current use of active
      surveillance in Spain and to identify areas for potential improvement. METHODS: A
      questionnaire generated by the Platform for Multicentre Studies of the Spanish
      Urology Association (AEU/PIEM/2014/0001, NCT02865330) was sent to all associate
      researchers from January to March 2016. The questionnaire included 7 domains
      covering various aspects of active surveillance. RESULTS: Thirty-three of the 41
      associate researchers responded to the questionnaire. Active surveillance is
      mainly controlled by the urology departments (87.9%). There was considerable
      heterogeneity in the classical clinical-pathological variables as selection
      criteria. Only 36.4% of the associate researchers used prostate-specific antigen
      density (PSAd). Multiparametric magnetic resonance imaging (mpMRI) was clearly
      underused as initial staging (6%). Only 27.3% of the researchers stated that
      their radiology colleagues had a high level of experience in mpMRI. In terms of
      the confirmation biopsy, most of the centres used the transrectal pathway, and
      only 2 out of 33 used the transperineal pathway or fusion software. Half of the
      researchers interviewed applied active treatment when faced with disease
      progression to Gleason 7 (3+4). There was no consensus on when to transition to
      an observation strategy. CONCLUSIONS: The study showed the underutilisation of
      informed consent and quality-of-life questionnaires. PSAd was not included as a
      decisive element in the initial strategy for most researchers. There was a lack
      of confidence in the urologists' mpMRI experience and an underutilisation of the
      transperineal pathway. There was also no consensus on the follow-up protocols and
      active treatment criteria, confirming the need for prospective studies to analyse
      the role of mpMRI and biomarkers.

PMID- 29661509
TI  - Distraction osteogenesis in the surgical management of syndromic
      craniosynostosis: a comprehensive review of published papers.
AB  - Our aim was to summarise current published evidence about the prognosis of
      various techniques of craniofacial distraction osteogenesis, particularly its
      indications, protocols, and complications. Published papers were acquired from
      online sources using the keywords "distraction osteogenesis", "Le Fort III",
      "monobloc", and "syndromic craniosynostosis" in combination with other keywords,
      such as "craniofacial deformity" and "midface". The search was confined to
      publications in English, and we followed the guidelines of the PRISMA statement.
      We found that deformity of the skull resulted mainly from Crouzon syndrome.
      Recently craniofacial distraction has been achieved by monobloc distraction
      osteogenesis using an external distraction device during childhood, while Le Fort
      III distraction osteogenesis was used in maturity. Craniofacial distraction was
      indicated primarily to correct increased intracranial pressure, exorbitism, and
      obstructive sleep apnoea in childhood, while midface hypoplasia was the main
      indication in maturity. Overall the most commonly reported complications were
      minor inflammatory reactions around the pins, and anticlockwise rotation when
      using external distraction systems. The mean amount of bony advancement was
      12.3mm for an external device, 18.6mm for an internal device and 18.7mm when both
      external and internal devices were used. Treatment by craniofacial distraction
      must be validated by long-term studies as there adequate data are lacking,
      particularly about structural relapse and the assessment of function.

PMID- 29661510
TI  - CFTR rescue with VX-809 and VX-770 favors the repair of primary airway epithelial
      cell cultures from patients with class II mutations in the presence of
      Pseudomonas aeruginosa exoproducts.
AB  - BACKGROUND: Progressive airway damage due to bacterial infections, especially
      with Pseudomonas aeruginosa remains the first cause of morbidity and mortality in
      CF patients. Our previous work revealed a repair delay in CF airway epithelia
      compared to non-CF. This delay was partially prevented after CFTR correction
      (with VRT-325) in the absence of infection. Our goals were now to evaluate the
      effect of the Orkambi combination (CFTR VX-809 corrector + VX-770 potentiator) on
      the repair of CF primary airway epithelia, in infectious conditions. METHODS:
      Primary airway epithelial cell cultures from patients with class II mutations
      were mechanically injured and wound healing rates and transepithelial resistances
      were monitored after CFTR rescue, in the absence and presence of P. aeruginosa
      exoproducts. RESULTS: Our data revealed that combined treatment with VX-809 and
      VX-770 elicited a greater beneficial impact on airway epithelial repair than VX
      809 alone, in the absence of infection. The treatment with Orkambi was effective
      not only in airway epithelial cell cultures from patients homozygous for the
      F508del mutation but also from heterozygous patients carrying F508del and another
      class II mutation (N1303 K, I507del). The stimulatory effect of the Orkambi
      treatment was prevented by CFTR inhibition with GlyH101. Finally, Orkambi
      combination elicited a slight but significant improvement in airway epithelial
      repair and transepithelial resistance, despite the presence of P. aeruginosa
      exoproducts. CONCLUSIONS: Our findings indicate that Orkambi may favor airway
      epithelial integrity in CF patients with class II mutations. Complementary
      approaches would however be needed to further improve CFTR rescue and airway
      epithelial repair.

PMID- 29661511
TI  - Developments in cystic fibrosis personalised epithelial assays: Science and
      patient perspectives.

PMID- 29661512
TI  - Organelle survival in a foreign organism: Hydra nematocysts in the flatworm
      Microstomum lineare.
AB  - Nematocysts are characteristic organelles of the phylum cnidaria. They are
      designated kleptocnidae when sequestered in animals that feed on cnidaria.
      Kleptocnidae are known for more than a century. Nevertheless it is still
      enigmatic how selected nematocyst types survive in the predator and how they
      reach their final destination in the foreign body. In the free-living
      Platyhelminth Microstomum lineare the fate of nematocysts of the prey Hydra
      oligactis was analyzed at the ultrastructural level and by fluorescence
      microscopy using hydra polyps that had been stained in vivo with the fluorescent
      dyes TROMI and TRITC. M. lineare digested hydra tissue in its intestine within 30
      min and all nematocyst types were phagocytosed without adherent cytoplasm by
      intestinal cnidophagocytes. Desmoneme and isorhiza nematocysts were digested
      whereas cnidophagocytes containing the venom-loaded stenotele nematocysts started
      to migrate out of the intestinal epithelia through the parenchyma to the
      epidermis thereby traversing the subintestinal and subepidermal muscle layer.
      Within one to two days, M. lineare began to form a muscle layer basolateral
      around epidermal cnidophagocytes. Epidermal stenoteles survived in M. lineare for
      at least four weeks. The ability of epidermal stenotele nematocysts to discharge
      suggest that this hydra organelle preserved its physiological properties in the
      new host.

PMID- 29661513
TI  - Cinnamon: A systematic review of adverse events.
AB  - Cinnamon, from the genus Cinnamomum and Lauraceae family, has been used as a
      popular spice for thousands of years around the world. Many studies have shown
      therapeutic effects of cinnamon including its antimicrobial, antiviral,
      antifungal, antioxidant, antitumor, antihypertensive, antilipemic, antidiabetic,
      gastroprotective, and immunomodulatory effects. Due to popular use of cinnamon
      and several human reports on adverse events associated with short or long term
      use of cinnamon, we aimed to systematically review its human reports of adverse
      event. Databases including Medline, Scopus, Science Direct, Embase, PubMed
      Central and Google scholar were searched using the key words "cinnamon" or
      "cinnamomum" for clinical trials, case reports and case series. Also spontaneous
      reports about adverse effects of cinnamon were collected from five national and
      international spontaneous reporting schemes. Thirty eight clinical trials were
      found, five of them reported adverse events. Twenty case reports and seven case
      series, as well as, spontaneous reports including 160 adverse events were also
      included. The most frequent adverse events were gastrointestinal disorders and
      allergic reactions which were self-limiting in the majority of cases. The
      available data suggests that despite the safety of cinnamon use as a spice and/or
      flavoring agent, its use may be associated with significant adverse effects in
      medicinal uses with larger doses or longer duration of use and should be
      clinically monitored.

PMID- 29661514
TI  - To Train or Not to Train: Admission of Pediatricians into Pediatric
      Rehabilitation Medicine Fellowships.

PMID- 29661515
TI  - The Role of Physiatrists in Natural Disasters.

PMID- 29661517
TI  - Potentials of the Potential: The "Lower, Slower, and Brighter" Mantra.

PMID- 29661516
TI  - Lisdexamfetamine Targets Amygdala Mechanisms That Bias Cognitive Control in
      Attention-Deficit/Hyperactivity Disorder.
AB  - BACKGROUND: Prefrontal-limbic circuits that form the neural architecture for
      emotion to influence behavior have been implicated in the pathophysiology of
      attention-deficit/hyperactivity disorder (ADHD) and represent a potentially
      important target of medication treatment that has not been substantively
      evaluated. This study tested the effect of the psychostimulant prodrug
      lisdexamfetamine dimesylate on amygdala activation and connectivity during the
      emotional bias of response execution and inhibition. METHODS: Twenty-five adults
      with ADHD were scanned twice with event-related functional magnetic resonance
      imaging while performing an emotional go/no-go task after 3 to 4 weeks of
      lisdexamfetamine treatment and 3 weeks off medication in a randomized,
      counterbalanced, hybrid crossover design. Drug, trial type, and face emotion
      (happy, sad, or neutral) were included as within-subjects factors in repeated
      measures analyses of activation and connectivity. RESULTS: Lisdexamfetamine was
      associated with increased right amygdala activation and reduced
      psychophysiological interactions with the orbital aspect of the left inferior
      frontal gyrus specifically for responses to sad faces compared with placebo, but
      there was no effect on the accuracy of response execution or inhibition. The
      relative gain in right amygdala activation in response to sad faces for
      lisdexamfetamine was correlated with a reduction in symptoms of ADHD.
      CONCLUSIONS: Treatment with lisdexamfetamine potentiates affective encoding in
      amygdala, purportedly via catecholaminergic mechanisms, but functionally
      disconnects the amygdala from inferior frontal regions that encode behavioral
      significance-resulting in reduced emotional bias of cognitive control.
      Pinpointing the neurophysiologic underpinnings of therapeutic improvement with
      lisdexamfetamine represents a first step in developing targeted approaches to
      treatment of ADHD.

PMID- 29661518
TI  - Radiation Risk Associated With X-Ray Mammography Screening: Communication and
      Exchange of Information via Tweets.

PMID- 29661519
TI  - Medically Engineered Solutions in Health Care: A Technology Incubator and Design
      Thinking Curriculum for Radiology Trainees.

PMID- 29661520
TI  - Utilization Trends in Diagnostic Imaging for a Commercially Insured Population: A
      Study of Massachusetts Residents 2009 to 2013.
AB  - PURPOSE: To report utilization trends in diagnostic imaging among commercially
      insured Massachusetts residents from 2009 to 2013. MATERIALS AND METHODS: Current
      Procedural Terminology codes were used to identify diagnostic imaging claims in
      the Massachusetts All-Payer Claims Database for the years 2009 to 2013. We
      reported utilization and spending annually by imaging modality using total
      claims, claims per 1,000 individuals, total expenditures, and average per claim
      payments. RESULTS: The number of diagnostic imaging claims per insured MA
      resident increased only 0.6% from 2009 to 2013, whereas nonradiology claims
      increased by 6% annually. Overall diagnostic imaging expenditures, adjusted for
      inflation, were 27% lower in 2009 than 2013, compared with an 18% increase in
      nonimaging expenditures. Average payments per claim were lower in 2013 than 2009
      for all modalities except nuclear medicine. Imaging procedure claims per 1,000 MA
      residents increased from 2009 to 2013 by 13% in MRI, from 147 to 166; by 17% in
      ultrasound, from 453 to 530; and by 12% in radiography (x-ray), from 985 to
      1,100. However, CT claims per 1,000 fell by 37%, from 341 to 213, and nuclear
      medicine declined 57%, from 89 claims per 1,000 to 38. CONCLUSION: Diagnostic
      imaging utilization exhibited negligible growth over the study period. Diagnostic
      imaging expenditures declined, largely the result of falling payments per claim
      in most imaging modalities, in contrast with increased utilization and spending
      on nonimaging services. Utilization of MRI, ultrasound, and x-ray increased from
      2009 to 2013, whereas CT and nuclear medicine use decreased sharply, although CT
      was heavily impacted by billing code changes.

PMID- 29661521
TI  - Retention Concerns About MR Studies Using Gadolinium-Based Contrast Agents.

PMID- 29661522
TI  - 'You are what you eat' (not what you said you ate yesterday): Why a one-off 24
      hour dietary recall fails capture usual dietary intake in schizophrenia.

PMID- 29661523
TI  - A positive-psychological intervention reduces acute psychosis-proneness.
AB  - BACKGROUND: While individuals at ultra-risk for schizophrenia are characterized
      by high negative/disorganised but low positive schizotypy, schizophrenia patients
      are usually high in all three schizotypy facets. Thus, avoiding increases in
      positive schizotypy in ultra-high risk individuals may constitute of form of
      schizophrenia-prevention. A possible method of reducing positive schizotypy could
      be Positive-Psychological intervention (PI). METHODS: We present results from 2
      independent studies, including a 12-month follow-up from study 1, using an easy
      to-perform intervention based on Positive Psychology to reduce positive
      schizotypy. RESULTS: A PI can significantly and sustainably reduce positive
      schizotypy compared to a placebo-condition. Furthermore, our results show very
      high response-rates to said intervention, with responsiveness to the intervention
      increasing significantly with disorganised schizotypic traits. CONCLUSIONS: As
      especially disorganised schizotypy is of relevance for the risk of transition
      from high benign schizotypy to schizophrenia and is found most closely associated
      to familial schizophrenia-risk and highly elevated in at-risk mental states, our
      results are encouraging. We suggest, thus, that positive psychology can not only
      reduce positive schizotypy, but may be increasingly useful with rising
      schizophrenia-risk and, thus, be worthy of further investigation regarding it
      potential in schizophrenia-prevention.

PMID- 29661524
TI  - Expressed emotion as a predictor of the first psychotic episode - Results of the
      European prediction of psychosis study.
AB  - OBJECTIVE: To investigate the impact of expressed emotion (EE) on the risk of
      developing the first psychotic episode (FEP). METHOD: The European Prediction of
      Psychosis Study (EPOS) investigated 245 patients who were at clinical high risk
      (CHR) of psychosis. The predictive value of EE alone and as a part of the
      multivariate EPOS model was evaluated. RESULTS: "Perceived irritability", a
      domain of the Level of Expressed Emotion Scale (LEE), was found to be predictive
      for the First Psychotic Episode (FEP), even as an individual variable.
      Furthermore, it was selected in the multivariate EPOS prediction model, thereby
      replacing two of the original predictor variables. This led to an improved
      revised version that enabled the identification of three significantly different
      risk classes with a hazard rate of up to 0.911. CONCLUSIONS: CHR subjects who
      perceive the most important person in their individual social environment to be
      limited in their stress coping skills had a higher risk of conversion to the
      first psychotic episode. The importance of this risk factor was further
      demonstrated by an improvement of risk estimation in the original EPOS predictor
      model. Perceiving a reference person as stress-prone and thus potentially
      unreliable might amplify self-experienced uncertainty and anxiety, which are
      often associated with the prodromal phase. Such an enforcement of stress-related
      processes could promote a conversion to psychosis.

PMID- 29661525
TI  - A Preliminary Study of Left Ventricular Rotational Mechanics in Children with
      Noncompaction Cardiomyopathy: Do They Influence Ventricular Function?
AB  - BACKGROUND: Current diagnostic criteria for noncompaction cardiomyopathy (NCC)
      lack specificity, and the disease lacks prognostic indicators. Reverse apical
      rotation (RAR) with abnormal rotation of the cardiac apex in the same clockwise
      direction as the base has been described in adults with NCC. The aim of this
      study was to test the hypothesis that RAR might differentiate between symptomatic
      NCC and benign hypertrabeculations and might be associated with ventricular
      dysfunction. METHODS: Echocardiograms from 28 children with NCC without cardiac
      malformations were prospectively compared with those from 29 age-matched normal
      control subjects. A chart review was performed to identify the patients'
      histories and clinical characteristics. Speckle-tracking was used to measure
      longitudinal strain, circumferential strain, and rotation. RESULTS: RAR occurred
      in 39% of patients with NCC. History of left ventricular (LV) dysfunction or
      arrhythmia was universal in, but not exclusive to, patients with RAR. Patients
      with RAR had lower LV longitudinal strain but similar ejection fractions compared
      with patients without RAR (median, -15.6% [interquartile range, -12.9% to -19.3%]
      vs -19% [interquartile range, -14.5% to -21.9%], P < .01; 53% [interquartile
      range, 43% to 68%] vs 61% [interquartile range, 58% to 67%], P = .08). Only a
      pattern of contraction with RAR, early arrest of twisting by mid-systole, and
      premature untwisting was associated with lower ejection fraction (46%;
      interquartile range, 43% to 52%; P = .006). CONCLUSIONS: RAR is not a sensitive
      but is a specific indicator of complications in children with NCC. Therefore, RAR
      may have prognostic rather than diagnostic value. Premature untwisting of the
      left ventricle during ejection may be an even more worrisome indicator of LV
      dysfunction.

PMID- 29661526
TI  - A Retrieval Analysis of Impingement in Dual-Mobility Liners.
AB  - BACKGROUND: Implant-related impingement is likely a major causative factor of
      total hip arthroplasty (THA) instability. Dual-mobility (DM) cups can
      theoretically improve stability in THA, but impingement rates with DM cups are
      not well studied. We examined retrieved DM THA liners to determine if less
      evidence existed for prosthetic impingement between the neck and the polyethylene
      liner than historical studies from our institution on fixed-bearing THAs.
      METHODS: DM components from 93 THAs were identified from 164 THAs whose DM
      components were revised between 2008 and 2015 through our institutional review
      board-approved implant retrieval program. The mean age was 63 +/- 11 years, mean
      body mass index was 30 +/- 7 kg/m2, and mean length of implantation was 2.08 +/-
      1.89 years. Two independent graders scored each liner for the presence and
      severity of impingement. Radiographs were evaluated for inclination, anteversion,
      change in leg length, and combined offset. RESULTS: Only 21.5% (20/93) of DM cups
      showed evidence of impingement compared to 77% (75/97) of fixed-bearing cups
      found in a previous study performed at our institution (P < .001). Of the
      revision components, 35.2% (5/14) demonstrated evidence of impingement compared
      to 19.7% (14/71) implanted in primary surgery (P = .189). In the cohort revised
      for instability, the rate of impingement was 35.3% (6/17); for the implants
      revised for any other reason, the impingement rate was 18.4% (14/77) (P = .126).
      CONCLUSION: This study demonstrates that DM liners significantly reduce the rate
      of impingement (21.5%) when compared to fixed-bearing liners (77%).

PMID- 29661527
TI  - Variability in Elongation and Failure of the Medial Collateral Ligament After Pie
      Crusting With 16- and 18-Gauge Needles.
AB  - BACKGROUND: In knee arthroplasty with preoperative varus deformity, medial
      collateral ligament (MCL) release may be needed to achieve balance. Pie-crusting
      allows for controlled release, but questions remain regarding its ability to
      obtain predictable results. We compared 16- vs18-gauge needle punctures and
      determined the number of punctures required to (1) lengthen the MCL by 1 mm and
      (2) cause ligament failure. METHODS: Thirteen knees were dissected, leaving the
      femur and tibia with an isolated MCL, and randomly assigned to 16- or 18-gauge
      groups. Initial stiffness was assessed by cycling the ligament to 300 N for 5
      cycles. The selected needle was used to make 10 punctures centered over the area
      of greatest tension. Cyclic testing was repeated after each set of punctures.
      Changes in MCL length and stiffness were measured. This process was repeated
      until failure. RESULTS: No differences occurred between the 16- and 18-gauge
      groups in cross-sectional area, initial stiffness, number of punctures to
      lengthen the MCL by 1 mm, or number of punctures to failure. As the number of
      punctures increased, a linear increase in elongation and decrease in stiffness
      occurred. CONCLUSION: Needle size was not the influencing factor. Variability in
      number of punctures, regardless of needle size, to elongate or fail the MCL shows
      the difficulty in developing a reproducible pie-crusting technique. This suggests
      that a standard number of punctures do not achieve controlled MCL lengthening for
      all patients, but that the number of punctures needed can be calculated for an
      individual knee based on the initial elongation after 10 punctures.

PMID- 29661528
TI  - Meropenem time above the MIC exposure is predictive of response in cystic
      fibrosis children with acute pulmonary exacerbations.
AB  - Meropenem exposures from 15 children (8-17 years old) with cystic fibrosis (CF)
      acute pulmonary exacerbation were analyzed to define the pharmacodynamic
      threshold required for a positive response. The primary endpoint was the relative
      increase in forced expiratory volume in 1 s (?FEV1) between pre- and
      posttreatment. Meropenem pharmacodynamic indices (fT > MIC, fAUC/MIC, fCmin/MIC)
      over the first 24 h were estimated for each participant based on their individual
      parameter estimates and the isolated pathogen with the highest meropenem MIC.
      Pseudomonas aeruginosa was the most common pathogen (n = 11/15). The mean +/- SD
      ?FEV1 was 18.8% +/- 11.3% posttreatment. The mean (range) fT > MIC exposure was
      63% (0-100%). An Emax model determined a significant relationship between fT >
      MIC and ?FEV1 (r2 = 0.8, P < 0.0004). 65% fT > MIC was a significant predictor of
      response; the median (25th, 75th %) ?FEV1 was 28.5% (22.2%, 31.7%) in those
      patients who achieved above 65% fT > MIC and 7.8% (1.1%, 12.6%) in those at or
      below 65% fT > MIC (P = 0.001). This is the first study in CF children to link
      meropenem exposure with a positive response as measured by ?FEV1. Larger studies
      are required to confirm this exposure threshold.

PMID- 29661529
TI  - In vitro activity of tedizolid and comparator agents against clinical Gram
      positive isolates recovered from patients with cancer.
AB  - A total of 248 Gram-positive isolates from cancer patients were tested for in
      vitro susceptibility to tedizolid and 3 comparator agents using CLSI broth
      microdilution methodology. Tedizolid inhibited 97% of isolates at <=0.5MUg/ml. It
      was active against all Gram-positive species and consistently had 8 fold lower
      MICs than linezolid, although based on % susceptibility using CLSI breakpoints,
      most isolates were also susceptible to the comparators. Tedizolid was active
      against MRSA isolates with vancomycin MICs of >=1.0MUg/ml.

PMID- 29661530
TI  - Targeted Protein Degradation: Unlocking the Therapeutic Proteome.

PMID- 29661531
TI  - Individual chamber segmentation in congenital heart disease.

PMID- 29661532
TI  - Measurement of physical performance by field tests in programs of cardiac
      rehabilitation: a systematic review and meta-analysis.
AB  - INTRODUCTION: The literature concerning the effects of cardiac rehabilitation
      (CR) on field tests results is inconsistent. PURPOSE: To perform a systematic
      review with meta-analysis on field tests results after programs of CR. METHODS:
      Studies published in PubMed and Web of Science databases until May 2016 were
      analyzed. The standard difference in means correct by bias (Hedges' g) was used
      as effect size (g) to measure que amount of modifications in performance of field
      tests after CR period. Potential differences between subgroups were analyzed by Q
      test based on ANOVA. RESULTS: Fifteen studies published between 1996 e 2016 were
      included in the review, 932 patients and age ranged 54,4 - 75,3 years old.
      Fourteen studies used the six-minutes walking test to evaluate the exercise
      capacity and one study used the Shuttle Walk Test. The random Hedges's g was
      0.617 (P<0.001), representing a drop of 20% in the performance of field test
      after CR. The meta-regression showed significantly association (P=0.01) to
      aerobic exercise duration, i.e., for each 1-min increase in aerobic exercise
      duration, there is a 0.02 increase in effect size for performance in the field
      test. CONCLUSION: Field tests can detect physical modification after CR, and the
      large duration of aerobic exercise during CR was associated with a better result.

PMID- 29661533
TI  - Design, synthesis, and evaluation of novel N-1 fluoroquinolone derivatives:
      Probing for binding contact with the active site tyrosine of gyrase.
AB  - Structural studies of topoisomerase-fluoroquinolone-DNA ternary complexes
      revealed a cavity between the quinolone N-1 position and the active site
      tyrosine. Fluoroquinolone derivatives having positively charged or aromatic
      moieties extended from the N-1 position were designed to probe for binding
      contacts with the phosphotyrosine residue in ternary complex. While alkylamine,
      alkylphthalimide, and alkylphenyl groups introduced at the N-1 position afforded
      derivatives that maintained modest inhibition of the supercoiling activity of DNA
      gyrase, none retained ability to poison DNA gyrase. Thus, the addition of a large
      and/or long moiety at the N-1 position disrupts ternary complex formation, and
      retained ability to inhibit supercoiling is likely through interference with the
      strand breakage reaction. Two derivatives were found to possess inhibitory
      effects on the decatenation activity of human topoisomerase II.

PMID- 29661534
TI  - A new Chlorin formulation promotes efficient photodynamic action in
      choriocapillaris of rabbit's eyes.
AB  - Age-related macular degeneration (AMD) as well as other choroidal diseases,
      demand novel therapeutic methods. Photodynamic therapy (PDT), which uses light
      and photosensitizer (PS) to cause specific vascular occlusion in the macula, is
      an interesting alternative. The only drug approved for the PDT treatment of AMD
      (Verteporfin) has a natural tendency to aggregate, demanding an expensive
      separation procedure during purification. We report a novel and affordable PS
      that is intrinsically protected against aggregation, the Monomeric Chlorin at
      High Concentration (MCHC-Chlorin), whose liposomal formulation was developed to
      provoke effective photodynamic action on the choroidal vasculature. Our report
      starts by stablishing the conditions to allow the efficient synthesis of MCHC
      Chlorin in high yields (92%). We then tested the light stimulated occlusion of
      choriocapillary vessels in rabbit's eyes induced by the two MCHC-Chlorin isomers,
      which are directly obtained from the synthetic route. The PS formulation was
      infused in the rabbit's ear vein and eyes were immediately irradiated at 650 nm.
      Indirect ophthalmoscopy, fundus photography, fluorescein angiography and
      histopathological evaluations were used to evaluate levels of photo-thrombosis
      and collateral damage. Choriocapillary occlusion was achieved in all treated
      rabbits' eyes, while retina and sclera were completely preserved. There was no
      photochemical reaction in none of the eyes that received LASER without PS. Both
      MCHC-Chlorin isomers were separately tested and exhibited similar positive
      results with no systemic toxicity. Therefore, PDT occurred equally well in all
      treated eyes and none of the controls showed any effect in the ophthalmological
      exams. MCHC-Chlorin offers great potential and should be further studied as an
      alternative drug for choroidal diseases.

PMID- 29661535
TI  - Synthesis of carbon-11-labeled 5-HT6R antagonists as new candidate PET
      radioligands for imaging of Alzheimer's disease.
AB  - Carbon-11-labeled serotonin (5-hydroxytryptamine) 6 receptor (5-HT6R)
      antagonists, 1-[(2-bromophenyl)sulfonyl]-5-[11C]methoxy-3-[(4-methyl-1
      piperazinyl)methyl]-1H-indole (O-[11C]2a) and 1-[(2-bromophenyl)sulfonyl]-5
      methoxy-3-[(4-[11C]methyl-1-piperazinyl)methyl]-1H-indole (N-[11C]2a), 5
      [11C]methoxy-3-((4-methylpiperazin-1-yl)methyl)-1-(phenylsulfonyl)-1H-indole (O
      [11C]2b) and 5-methoxy-3-((4-[11C]methylpiperazin-1-yl)methyl)-1-(phenylsulfonyl)
      1H-indole (N-[11C]2b), 1-((4-isopropylphenyl)sulfonyl)-5-[11C]methoxy-3-((4
      methylpiperazin-1-yl)methyl)-1H-indole (O-[11C]2c) and 1-((4
      isopropylphenyl)sulfonyl)-5-methoxy-3-((4-[11C]methylpiperazin-1-yl)methyl)-1H
      indole (N-[11C]2c), 1-((4-fluorophenyl)sulfonyl)-5-[11C]methoxy-3-((4
      methylpiperazin-1-yl)methyl)-1H-indole (O-[11C]2d) and 1-((4
      fluorophenyl)sulfonyl)-5-methoxy-3-((4-[11C]methylpiperazin-1-yl)methyl)-1H
      indole (N-[11C]2d), were prepared from their O- or N-desmethylated precursors
      with [11C]CH3OTf through O- or N-[11C]methylation and isolated by HPLC combined
      with SPE in 40-50% radiochemical yield, based on [11C]CO2 and decay corrected to
      end of bombardment (EOB). The radiochemical purity was >99%, and the molar
      activity (MA) at EOB was 370-740 GBq/MUmol with a total synthesis time of ~40-min
      from EOB.

PMID- 29661536
TI  - Thioether-bridged arylalkyl-linked N-phenylpyrazole derivatives: Design,
      synthesis, insecticidal activities, structure-activity relationship and molecular
      modeling studies.
AB  - Owing to thioether diverse physicochemical properties by non-covalent
      interactions with bio-macromolecules, thioether derivatives containing
      heterocyclic moiety are known for their interesting insecticidal bioactivities
      and attracting considerable attention as neuroactive insecticides. Here we
      synthesis a series of novel thioether bridged N-phenylpyrazole derivatives
      incorporating various (hetero)aromatic substituents into 4-position of the
      pyrazole ring. Structure-activity relationship (SAR) studies resulted in
      compounds 6d and 7d with the most potent insecticidal activity among the series
      containing various substituted benzene substituents (LC50 = 13.70-25.47 MUg/g).
      Further optimization to increase the lipophilicity and charge density of aromatic
      substituents of compounds 6d and 7d resulted in compounds 12d, 14d and 16d with
      sulfur-containing heterocycle substituents possessing good insecticidal activity
      against Musca domestica L. among the series (LC50 = 0.67-1.30 MUg/g). The
      thioether bridge N-phenylpyrazole derivatives, which exhibit different length of
      the spacer arm introduced between N-phenylpyrazole moiety and the
      (hetero)aromatic substituents, were also prepared and evaluated. By contrast, the
      insecticidal activities of compounds containing the short thioether bridge, 1,2
      bis((hetero)aromatic thio) ethane, are higher than that containing the long
      thioether bridge, 1,3-bis((hetero)aromatic thio) propane. The results of
      molecular docking and pharmacophore analyses indicated A299, T303, and L306 of a
      subunit were essential to form non-covalent interactions contacts with the
      ligands. Specially, the sulfur-containing heterocycle substituent derivatives 12d
      and 14d as the sterically favored areas could form the important hydrophobic
      interactions with the deeper residue P295.

PMID- 29661538
TI  - An unusual case of anti-MOG CNS demyelination with concomitant mild anti-NMDAR
      encephalitis.
AB  - We report the case of a patient who presented with progressive unsteadiness and
      narcoleptic attacks followed by behavioral change and psychosis, without visual
      disturbances or seizures. MRI revealed multiple areas of fluid attenuation
      inversion recovery (FLAIR) high-intensity lesions involving the cerebellum,
      brainstem, thalamus and third ventricular peri-ependymal region consistent with
      demyelination. Both the serum myelin oligodendrocyte glycoprotein-antibodies (MOG
      Abs) and cerebral spinal fluid (CSF) anti-N-methyl-d-as-partate receptor (NMDAR)
      antibodies were positive using transfected cell based assays. The patient
      presented simultaneously with symptoms of MOG antibody disease and anti-NMDAR
      encephalitis, an unusual clinical scenario, indicating the co-existence of the
      two disorders.

PMID- 29661537
TI  - Pyridoxine dependent epilepsy: Is late onset a predictor for favorable outcome?
AB  - AIM: In pyridoxine dependent epilepsy (PDE), patients usually present with
      neonatal seizures. A small subgroup is characterized by late-onset beyond 2
      months of age. We aim to analyze the observation of relatively good cognitive
      outcome in this subgroup of late-onset PDE patients. METHODS: We retrospectively
      analyzed data from four metabolically and genetically confirmed late-onset
      patients with PDE due to antiquitin (ALDH7A1) deficiency. Data were analyzed
      regarding ALDH7A1 mutations, alpha-Aminoadipic semialdehyde (alpha-AASA) and
      pipecolic acid (PA) levels, medication during pregnancy, delivery, treatment
      delay, amount of seizures, pyridoxine dose, adjuvant therapy and findings on
      brain MRI. RESULTS: Results showed that three patients had relatively good
      outcome (IQ 80-97), while one patient did not undergo formal testing and was
      considered mildly delayed. We were unable to find a clear association between the
      above-mentioned variables and cognitive outcome, although a less severe genotype
      may be present in three patients, and maternal medication could be accountable
      for better outcome in two patients. INTERPRETATION: We suggest that favorable
      outcome in late onset PDE might be explained by a combination of factors. A yet
      unknown protective factor, different genetic variations, functional variation and
      secondarily variation in treatment regimens and absence of neonatal seizure
      induced brain damage.

PMID- 29661539
TI  - miR-548k regulates CXCL13 expression in myasthenia gravis patients with thymic
      hyperplasia and in Jurkat cells.
AB  - Myasthenia gravis (MG) is a B cell-mediated and T cell-dependent autoimmune
      disease. Thymic hyperplasia has great significance for MG pathogenesis and
      treatment. MicroRNAs (miRNAs) are a newly recognized type of gene expression
      regulatory factor that regulate gene expression at the post-transcriptional
      level. Additionally, miRNAs are involved in immune regulation of the thymus and
      the occurrence and development of autoimmune diseases. In this study, we found 33
      miRNAs that were significantly dysregulated in thymic tissues from MG patients
      with thymus hyperplasia (MGH) compared with thymic tissues from normal controls
      using a miRNA microarray chip. We found a negative correlation between the miR
      548k and CXCL13 mRNA levels in a large set of samples using quantitative real
      time polymerase chain reaction (qRT-PCR). We found that the CXCL13 3'
      untranslated region (UTR) was a target of miR-548k using bioinformatics analysis.
      Next, we obtained direct evidence that CXCL13 is a target of miR-548k using a
      luciferase reporter assay. Finally, we demonstrated negative regulation between
      mir-548k and CXCL13 in Jurkat cells. Thus, miR-548k regulates the mRNA expression
      of its target gene CXCL13 in the thymus of MGH patients and plays an important
      role in MGH pathogenesis.

PMID- 29661540
TI  - MIF functional polymorphisms (-794 CATT5-8 and -173 G>C) are associated with MIF
      serum levels, severity and progression in male multiple sclerosis from western
      Mexican population.
AB  - Macrophage migration inhibitory factor (MIF) is a cytokine associated with tissue
      damage in multiple autoimmune diseases such as systemic lupus erythematosus,
      rheumatoid arthritis and psoriatic arthritis. The role of MIF in multiple
      sclerosis (MS) and the contribution of its polymorphisms are unknown in our
      population. Therefore, we decided to investigate the genetic association of -794
      CATT5-8 (rs5844572) and -173 G>C (rs755622) MIF polymorphisms with MS, clinical
      variables and MIF serum levels in the population of western Mexico. 230 MS
      patients diagnosed according to McDonald criteria and 248 control subjects (CS)
      were recruited for this study, both polymorphisms were genotyped by PCR and PCR
      RFLP and MIF serum levels were measured by ELISA kit. Severity and progression of
      MS were evaluated by EDSS and MSSS scores, respectively. Genotypes carrying the 5
      repeats alleles of -794 CATT5-8MIF polymorphism present higher MIF serum levels
      in comparison with no carriers, and the presence of 5,7 heterozygous genotype
      contribute to the increase of disease severity and damage progression in MS
      patients. Notably when we stratified by sex, an effect of risk alleles (7 repeats
      and -173*C) of both MIF polymorphisms on EDSS and MSSS scores on males was found
      (p < 0.01). This study suggests that polymorphic alleles of MIF polymorphisms
      could act as sex-specific disease modifiers that increase the severity and
      progression of MS in male Mexican-Mestizo western population.

PMID- 29661541
TI  - CKD and ESRD in US Hispanics.
AB  - Hispanics are the largest racial/ethnic minority group in the United States, and
      they experience a substantial burden of kidney disease. Although the prevalence
      of chronic kidney disease (CKD) is similar or slightly lower in Hispanics than
      non-Hispanic whites, the age- and sex-adjusted prevalence rate of end-stage renal
      disease is almost 50% higher in Hispanics compared with non-Hispanic whites. This
      has been attributed in part to faster CKD progression among Hispanics.
      Furthermore, Hispanic ethnicity has been associated with a greater prevalence of
      cardiovascular disease risk factors, including obesity and diabetes, as well as
      CKD-related complications. Despite their less favorable socioeconomic status,
      which often leads to limited access to quality health care, and their high
      comorbid condition burden, the risk for mortality among Hispanics appears to be
      lower than for non-Hispanic whites. This survival paradox has been attributed to
      a complex interplay between sociocultural and psychosocial factors, as well as
      other factors. Future research should focus on evaluating the long-term impact of
      these factors on patient-centered and clinical outcomes. National policies are
      needed to improve access to and quality of health care among Hispanics with CKD.

PMID- 29661543
TI  - Lunar and climatic effects on boar ejaculate traits.
AB  - There is evidence that phases of the moon affect wild animal behaviors including
      reproduction. There is, however, little evidence of moon phase effects on
      domestic livestock reproduction. This study investigated the effects of moon
      phase and climatic variables on boar ejaculate traits. Records of 4149 semen
      collections from boars of nine different breeds at one boar stud were used. The
      response variables were volume of ejaculate, concentration of sperm in the
      ejaculate, and number of doses obtained per ejaculate. Moon phase, greatest daily
      temperature (T), least daily T, average daily relative humidity (RH), temperature
      humidity index (THI), season and the interaction of moon phase with season were
      analyzed at the day of collection and 45 days prior to date of collection as a
      proxy of initiation of spermatogenesis. For both dates analyzed season and the
      interaction of season with moon had significant effects (P < 0.05) on the volume
      of the ejaculate. Moon phase had a significant effect (P < 0.05) on volume of
      ejaculate at the day of collection. Sperm concentration was affected (P < 0.05)
      by the interaction of moon phase with season, high and low temperature, THI, RH
      and breed. Season had an effect (P < 0.01) on concentration of sperm at the
      initiation of spermatogenesis. For doses that could be used for AI that were
      obtained/ejaculate, there were effects of moon phase, season, the interaction
      between season and moon phase and breed (P < 0.05) at collection day and at the
      initiation of spermatogenesis. There was an interaction (P < 0.0001) between
      season and moon phase for volume of ejaculate, sperm concentration and number of
      doses obtained per ejaculate at date of collection and at day of initiation of
      spermatogenesis. The significant interaction of season and moon phase on boar
      semen traits suggests that to maximize productivity of modern swine production
      systems determining a collection schedule in some seasons relative to moon phase
      may be advantageous.

PMID- 29661542
TI  - Helping Patients With ESRD and Earlier Stages of CKD to Quit Smoking.
AB  - Among the many adverse effects of tobacco exposure is the increased risk for
      progression of kidney disease. Individuals with chronic kidney disease (CKD), who
      already face increased cardiovascular event rates compared to the general
      population, are at even greater risk if they smoke. Despite these risks and the
      increased focus on smoking cessation in the general population in recent years,
      national guidelines have not specifically targeted individuals with CKD. There
      are similarly sparse data specific to individuals with CKD regarding the safety
      and efficacy of evidence-based smoking cessation modalities. This review aims to
      identify the risks of nicotine dependence in individuals with CKD and the
      potential benefits of smoking cessation; discuss current strategies for smoking
      cessation, including behavioral and pharmacologic therapies such as varenicline;
      and extrapolate these interventions to the unique challenges of this population.
      Much of the data presented stem from evidence for the general population but are
      described with additional consideration in dosing of nicotine replacement
      therapy, as well as non-nicotine pharmacotherapy and treatment modality for
      individuals with CKD.

PMID- 29661544
TI  - Renal cell carcinoma for the nephrologist.
AB  - Renal cell carcinoma (RCC), a malignancy whose incidence is increasing, is
      frequently encountered in general nephrology practice when acute and chronic
      kidney disease occurs in the course of disease. Importantly, when kidney disease
      develops in the setting of RCC, mortality is significantly increased with
      patients often dying of a non-cancer-related complication of kidney disease. As
      such, practicing nephrologists need to have a working knowledge of this cancer's
      biology, treatment, and complications. Nephrologists should be involved in all
      aspects of the care of patients with RCC including in the acute setting prior to
      nephrectomy and in the chronic setting for patients with post-nephrectomy chronic
      kidney disease and those receiving potentially nephrotoxic anti-cancer agents.
      This collaborative approach to RCC care will hopefully improve patient outcomes.

PMID- 29661545
TI  - A discussion paper: Do national maternity policy reviews take account of the
      education and training of the future midwifery workforce? An example from
      England.
AB  - The development and provision of maternity services globally are continuing to
      receive much attention in order to improve care and safety for women and babies.
      In the UK national reviews of the maternity services have taken place, with local
      services taking forward specific pilot projects to support the implementation of
      policy recommendations. This paper argues that, in order to meet the requirements
      of change in maternity services, there also needs to be a prompt review of the
      education of student midwives in order to be confident that the workforce of the
      future is equipped to implement these changes successfully. Using changes to
      national policy in England, this paper raises the question of the need for
      flexible national education standards, to ensure a curriculum can meet the needs
      of the changing workforce without the need for constant revision of the
      curriculum.

PMID- 29661546
TI  - Strategy for the accurate preoperative evaluation of the number of metastatic
      axillary lymph nodes in breast cancer.
AB  - BACKGROUND: After the ACOSOG Z0011 trial, it became important to evaluate the
      number of metastatic axillary lymph nodes (LNs) preoperatively. The purpose of
      this paper is to confirm whether the number of metastases can be accurately
      diagnosed by preoperative computed tomography (CT), ultrasound sonography (US),
      and US-guided fine-needle aspiration cytology (FNAC). METHODS: We retrospectively
      analyzed the axillary LNs finding of preoperative CT/US of 470 breast cancer
      patients. Metastasis was suspected based on the following findings: LNs with a
      long-axis diameter of >=10 mm or a short-axis diameter of >=5 mm on CT, and LNs
      with the absence of a fatty hilum, focal cortical thickness or a cortical
      thickness >=2 mm on US. We also examined the results of FNAC making a rapid
      bedside diagnosis (bedside-FNAC) of 162 LNs that were suspected to metastatic
      based on the US findings. RESULTS: On CT, all cases with >=3 LNs with a long-axis
      diameter of >=10 mm and a short-axis diameter of >=5 mm had metastasis. However,
      there was no relationship between the number of detected LNs and the number of
      metastases. On US, 75.7% of LNs with the absence of a fatty hilum and all LNs
      with cortical thickness >=6 mm had metastasis. The accuracy of bedside-FNAC for
      suspicious LNs was 100%. CONCLUSIONS: Although we can pick up LNs that are likely
      to have metastasis on CT/US, it was impossible to accurately predict the number
      of metastases on CT/US. However, bedside-FNAC of suspicious LNs could accurately
      predict the number of metastases.

PMID- 29661547
TI  - Influence of Injection Volume on Rate of Subsequent Intervention in Carpal Tunnel
      Syndrome Over 1-Year Follow-Up.
AB  - PURPOSE: The optimal volume and dose of corticosteroid injections for treatment
      of carpal tunnel syndrome (CTS) have not yet been established. It is unknown
      whether the volume of injectate influences the outcome of carpal tunnel
      injection. The purpose of this study was to assess whether there is an
      association between the volume of injectate and subsequent intervention in the
      treatment of CTS. METHODS: This study evaluated residents of Olmsted County, MN,
      who were treated with a corticosteroid injection for CTS between 2001 and 2010.
      Failure of treatment was the primary outcome, defined as a subsequent
      intervention: either a second injection or carpal tunnel release within 1 year of
      initial injection. General estimating equations logistic regression was used to
      assess the association between injectate volume and rate of treatment failure,
      adjusting for age, sex, effective dose of steroid, type of steroid injected,
      electrodiagnostic severity, and the presence of comorbidities such as rheumatoid
      arthritis, diabetes mellitus, peripheral neuropathy, and radiculopathy. RESULTS:
      There were 856 affected hands in 651 patients. A total of 56% (n = 484) of
      treated hands received subsequent treatment within 1 year. Multivariable analysis
      showed that a larger injectate volume was significantly associated with reduced
      rate of treatment failure within 1 year. Rheumatoid arthritis and ultrasound
      guided procedures were also associated with a reduced rate of treatment failure,
      whereas severe electrodiagnostic results were associated with an increased rate
      of failure. CONCLUSIONS: This study showed that a larger volume of corticosteroid
      injection is associated with reduced odds of subsequent intervention after a
      single corticosteroid injection in CTS. Further research is needed to determine
      the optimal volume for steroid injections in the treatment of CTS. TYPE OF
      STUDY/LEVEL OF EVIDENCE: Prognostic IV.

PMID- 29661548
TI  - Modal space three-state feedback control for electro-hydraulic servo plane
      redundant driving mechanism with eccentric load decoupling.
AB  - The shaking table based on electro-hydraulic servo parallel mechanism has the
      advantage of strong carrying capacity. However, the strong coupling caused by the
      eccentric load not only affects the degree of freedom space control precision,
      but also brings trouble to the system control. A novel decoupling control
      strategy is proposed, which is based on modal space to solve the coupling problem
      for parallel mechanism with eccentric load. The phenomenon of strong dynamic
      coupling among degree of freedom space is described by experiments, and its
      influence on control design is discussed. Considering the particularity of plane
      motion, the dynamic model is built by Lagrangian method to avoid complex
      calculations. The dynamic equations of the coupling physical space are
      transformed into the dynamic equations of the decoupling modal space by using the
      weighted orthogonality of the modal main mode with respect to mass matrix and
      stiffness matrix. In the modal space, the adjustments of the modal channels are
      independent of each other. Moreover, the paper discusses identical closed-loop
      dynamic characteristics of modal channels, which will realize decoupling for
      degree of freedom space, thus a modal space three-state feedback control is
      proposed to expand the frequency bandwidth of each modal channel for ensuring
      their near-identical responses in a larger frequency range. Experimental results
      show that the concept of modal space three-state feedback control proposed in
      this paper can effectively reduce the strong coupling problem of degree of
      freedom space channels, which verify the effectiveness of the proposed model
      space state feedback control strategy for improving the control performance of
      the electro-hydraulic servo plane redundant driving mechanism.

PMID- 29661549
TI  - Adaptive nonsingular terminal sliding mode controller for micro/nanopositioning
      systems driven by linear piezoelectric ceramic motors.
AB  - In the field of nanotechnology, there is a growing demand to provide precision
      control and manipulation of devices with the ability to interact with complex and
      unstructured environments at micro/nano-scale. As a result, ultrahigh-precision
      positioning stages have been turned into a key requirement of nanotechnology. In
      this paper, linear piezoelectric ceramic motors (LPCMs) are adopted to drive
      micro/nanopositioning stages since they have the ability to achieve high
      precision in addition to being versatile to be implemented over a wide range of
      applications. In the establishment of a control scheme for such manipulation
      systems, the presence of friction, parameter uncertainties, and external
      disturbances prevent the systems from providing the desired positioning accuracy.
      The work in this paper focuses on the development of a control framework that
      addresses these issues as it uses the nonsingular terminal sliding mode technique
      for the precise position tracking problem of an LPCM-driven positioning stage
      with friction, uncertain parameters, and external disturbances. The developed
      control algorithm exhibits the following two attractive features. First, upper
      bounds of system uncertainties/perturbations are adaptively estimated in the
      proposed controller; thus, prior knowledge about uncertainty/disturbance bounds
      is not necessary. Second, the discontinuous signum function is transferred to the
      time derivative of the control input and the continuous control signal is
      obtained after integration; consequently, the chattering phenomenon, which
      presents a major handicap to the implementation of conventional sliding mode
      control in real applications, is alleviated without deteriorating the robustness
      of the system. The stability of the controlled system is analyzed, and the
      convergence of the position tracking error to zero is analytically proven. The
      proposed control strategy is experimentally validated and compared to the
      existing control approaches.

PMID- 29661550
TI  - Persistently-exciting signal generation for Optimal Parameter Estimation of
      constrained nonlinear dynamical systems.
AB  - This work presents a novel methodology for Sub-Optimal Excitation Signal
      Generation and Optimal Parameter Estimation of constrained nonlinear systems. It
      is proposed that the evaluation of each signal must also account for the
      difference between real and estimated system parameters. However, this metric is
      not directly obtained once the real parameter values are not known. The
      alternative presented here is to adopt the hypothesis that, if a system can be
      approximated by a white box model, this model can be used as a benchmark to
      indicate the impact of a signal over the parametric estimation. In this way, the
      proposed method uses a dual layer optimization methodology: (i) Inner Level; For
      a given excitation signal a nonlinear optimization method searches for the
      optimal set of parameters that minimizes the error between the outputs of the
      optimized and benchmark models. (ii) At the outer level, a metaheuristic
      optimization method is responsible for constructing the best excitation signal,
      considering the fitness coming from the inner level, the quadratic difference
      between its parameters and the cost related to the time and space required to
      execute the experiment.

PMID- 29661551
TI  - Control of a manipulator robot by neuro-fuzzy subsets form approach control
      optimized by the genetic algorithms.
AB  - In this paper, we describe a new form of neuro-fuzzy-genetic controller design
      for nonlinear system derived from a manipulator robot. The proposed method
      combines fuzzy logic and neuronal networks which are of growing interest in
      robotics, the neuro-fuzzy controller does not require the knowledge of the robot
      parameters values. Furtheremore, the genetic algorithms (GAs) for complex motion
      planning of robots require an evaluation function which takes into account
      multiple factors. An optimizing algorithm based on the genetic algorithms is
      applied in order to provide the most adequate shape of the fuzzy subsets that are
      considered as an interpolation functions. The proposed approach provides a well
      learning of the manipulator robot dynamics whatever the assigned task. Simulation
      and practical results illustrate the effectiveness of the proposed strategy. The
      advantages of the proposed method and the possibilities of further improvements
      are discussed.

PMID- 29661552
TI  - Skin banking at a regional burns centre-The way forward.
AB  - In India approximately 1 million people get burnt every year and most of them are
      from the lower or middle income strata. Therefore it is obligatory to find out an
      economic way of treatment for the affected populace. Since use of human skin
      allograft is the gold standard for the treatment of burn wound, in-house skin
      banking for a burn unit hospital is prerequisite to make the treatment procedure
      affordable. Although, there was one skin bank at India till 2009, but it was
      difficult for a single bank to cover the entire country's need. Looking at the
      necessities, National Burns Centre (a tertiary burn care centre) along with
      Rotary International and Euro Skin Bank collaborated and developed an effective
      cadaveric skin banking model in Mumbai, Maharashtra in 2009. Initial two to three
      years were formation phase; by the year 2013 the entire system was organized and
      started running full fledged. The model has also been replicated in other states
      of India to accommodate the large burn population of the country. This paper
      therefore, gives a step by step account of how the bank evolved and its present
      status.

PMID- 29661553
TI  - Development of a contaminated ischemic porcine wound model and the evaluation of
      bromelain based enzymatic debridement.
AB  - OBJECTIVES: There are no well accepted animal models of chronic wounds, limiting
      advances in understanding and treatment of chronic ulcers. We developed a porcine
      wound model which combines multiple factors involved in chronic wounds to create
      a contaminated necrotic eschar and evaluated the debriding efficacy of a novel
      bromelain based enzymatic debriding agent (EscharEx). METHODS: Contaminated
      ischemic wounds were created on the flanks of domestic pigs by 'sandwiching' the
      skin between 2 'O' rings (1 placed on the surface of the skin and the other
      underneath the skin) for 24h prior to dermatomal excision of the necrotic eschar
      and its contamination with Staphylococcus aureus and Candida albicans. After
      confirming the development of infected eschars, additional animals were used to
      compare the effects of daily application of topical EscharEx or its hydrating
      vehicle on eschar debridement as a control. RESULTS: In all cases, application of
      the 'O' rings resulted in full thickness necrotic ecshars with invasive
      infections, which did not reepithelialize and sloughed off spontaneously within
      14-21 days. All wounds reepithelialized within 28-42 days forming contracted
      scars. All EscharEx treated eschars were completely debrided within 7-9 days,
      while no debridement was evident in eschars treated with the control gel.
      CONCLUSIONS: Our model simulates the initial phase of chronic wounds
      characterized by a contaminated necrotic eschar allowing evaluation of wound
      debriding agents, and that a bromelain-based debriding agent completely debrides
      the contaminated necrotic eschars within one week in this model.

PMID- 29661554
TI  - Effect of skin graft thickness on scar development in a porcine burn model.
AB  - Animal models provide a way to investigate scar therapies in a controlled
      environment. It is necessary to produce uniform, reproducible scars with high
      anatomic and biologic similarity to human scars to better evaluate the efficacy
      of treatment strategies and to develop new treatments. In this study, scar
      development and maturation were assessed in a porcine full-thickness burn model
      with immediate excision and split-thickness autograft coverage. Red Duroc pigs
      were treated with split-thickness autografts of varying thickness: 0.026in.
      ("thin") or 0.058in. ("thick"). Additionally, the thin skin grafts were meshed
      and expanded at 1:1.5 or 1:4 to evaluate the role of skin expansion in scar
      formation. Overall, the burn-excise-autograft model resulted in thick, raised
      scars. Treatment with thick split-thickness skin grafts resulted in less
      contraction and reduced scarring as well as improved biomechanics. Thin skin
      autograft expansion at a 1:4 ratio tended to result in scars that contracted more
      with increased scar height compared to the 1:1.5 expansion ratio. All treatment
      groups showed Matrix Metalloproteinase 2 (MMP2) and Transforming Growth Factor
      beta1 (TGF-beta1) expression that increased over time and peaked 4 weeks after
      grafting. Burns treated with thick split-thickness grafts showed decreased
      expression of pro-inflammatory genes 1 week after grafting, including insulin
      like growth factor 1 (IGF-1) and TGF-beta1, compared to wounds treated with thin
      split-thickness grafts. Overall, the burn-excise-autograft model using split
      thickness autograft meshed and expanded to 1:1.5 or 1:4, resulted in thick,
      raised scars similar in appearance and structure to human hypertrophic scars.
      This model can be used in future studies to study burn treatment outcomes and new
      therapies.

PMID- 29661555
TI  - Directly quantified dietary n-3 fatty acid intakes of Canadian toddlers are lower
      than current dietary recommendations.
AB  - To date, few studies have evaluated the intake of dietary n-3 polyunsaturated
      fatty acids (PUFA) in young North American children and current estimates are
      based on indirect approaches which have concerning limitations. Furthermore,
      there is a lack of available knowledge regarding the proportion of children
      meeting current dietary recommendations for the consumption of long-chain n-3
      PUFA as alpha-linolenic acid (ALA) and eicosapentaenoic acid
      (EPA)/docosahexaenoic acid (DHA). The objective of the present study was to
      directly quantify the intake of n-3 PUFA in toddlers aged 2 to 3 years and
      determine if intakes met international recommendations. Given the low intakes of
      fish in North America, we predicted that n-3 PUFA intakes in toddlers would fall
      short of recommended intakes. Duplicated diets were collected from 20 Canadian
      children over a 3-day period. Diets were then directly analyzed by gas
      chromatography. Daily intakes (means +/- SEM) of ALA, EPA, and DHA were as
      follows: 710.1 +/- 69.7, 9.6 +/- 2.9, and 19.2 +/- 6.8 mg/d, respectively.
      Compared with North American dietary reference intakes, 45% of our children met
      the minimal recommended intake of ALA, whereas only 5% consumed the target intake
      of EPA plus DHA. These results indicate that Canadian children aged 2 to 3 years
      struggle to consume adequate intakes of the n-3 PUFA ALA and particularly
      EPA/DHA; efforts to narrow this gap should focus on increasing EPA and DHA
      intakes by appropriate fish/seafood consumption along with enriched foods or
      supplements if necessary.

PMID- 29661556
TI  - Gastric Burkitt's lymphoma: A rare entity.

PMID- 29661557
TI  - A new therapy prevents intellectual disability in mouse with phenylketonuria.
AB  - Untreated phenylketonuria (PKU) results in severe neurodevelopmental disorders,
      which can be partially prevented by an early and rigorous limitation of
      phenylalanine (Phe) intake. Enzyme substitution therapy with recombinant Anabaena
      variabilis Phe Ammonia Lyase (rAvPAL) proved to be effective in reducing blood
      Phe levels in preclinical and clinical studies of adults with PKU. Aims of
      present study were: a) to gather proofs of clinical efficacy of rAvPAL treatment
      in preventing neurological impairment in an early treated murine model of PKU; b)
      to test the advantages of an alternative delivering system for rAvPAL such as
      autologous erythrocytes. BTBR-Pahenu2-/- mice were treated from 15 to 64 post
      natal days with weekly infusions of erythrocytes loaded with rAvPAL. Behavioral,
      neurochemical, and brain histological markers denoting untreated PKU were
      examined in early treated adult mice in comparison with untreated and wild type
      animals. rAvPAL therapy normalized blood and brain Phe; prevented cognitive
      developmental failure, brain depletion of serotonin, dendritic spine
      abnormalities, and myelin basic protein reduction. No adverse events or
      inactivating immune reaction were observed. In conclusion present study testifies
      the clinical efficacy of rAvPAL treatment in a preclinical model of PKU and the
      advantages of erythrocytes as carrier of the enzyme in term of frequency of the
      administrations and prevention of immunological reactions.

PMID- 29661558
TI  - Genetic assessment and folate receptor autoantibodies in infantile-onset cerebral
      folate deficiency (CFD) syndrome.
AB  - INTRODUCTION: Cerebral folate deficiency (CFD) syndromes are defined as neuro
      psychiatric conditions with low CSF folate and attributed to different causes
      such as autoantibodies against the folate receptor-alpha (FR) protein that can
      block folate transport across the choroid plexus, FOLR1 gene mutations or
      mitochondrial disorders. High-dose folinic acid treatment restores many
      neurologic deficits. STUDY AIMS AND METHODS: Among 36 patients from 33 families
      the infantile-onset CFD syndrome was diagnosed based on typical clinical features
      and low CSF folate. All parents were healthy. Three families had 2 affected
      siblings, while parents from 4 families were first cousins. We analysed serum FR
      autoantibodies and the FOLR1 and FOLR2 genes. Among three consanguineous families
      homozygosity mapping attempted to identify a monogenetic cause. Whole exome
      sequencing (WES) was performed in the fourth consanguineous family, where two
      siblings also suffered from polyneuropathy as an atypical finding. RESULTS: Boys
      (72%) outnumbered girls (28%). Most patients (89%) had serum FR autoantibodies
      fluctuating over 5-6 weeks. Two children had a genetic FOLR1 variant without
      pathological significance. Homozygosity mapping failed to detect a single
      autosomal recessive gene. WES revealed an autosomal recessive polynucleotide
      kinase 3'phosphatase (PNKP) gene abnormality in the siblings with polyneuropathy.
      DISCUSSION: Infantile-onset CFD was characterized by serum FR autoantibodies as
      its predominant pathology whereas pathogenic FOLR1 gene mutations were absent.
      Homozygosity mapping excluded autosomal recessive inheritance of any single
      responsible gene. WES in one consanguineous family identified a PNKP gene
      abnormality that explained the polyneuropathy and also its contribution to the
      infantile CFD syndrome because the PNKP gene plays a dual role in both
      neurodevelopment and immune-regulatory function. Further research for candidate
      genes predisposing to FRalpha-autoimmunity is suggested to include X-chromosomal
      and non-coding DNA regions.

PMID- 29661559
TI  - Stickler syndrome in children: a radiological review.
AB  - AIM: To review the radiological findings of the largest cohort to date of
      paediatric patients with Stickler syndrome, all with confirmed molecular genetic
      analysis and sub-typing. PATIENTS AND METHODS: It is understood that the National
      Health Service (NHS) commissioned service at Addenbrookes Hospital, Cambridge, UK
      has the largest cohort of Stickler syndrome patients in the paediatric age group
      worldwide with 240 registered children. Fifty-nine were assessed radiologically
      and for their genotypes. These radiographs were reviewed and 74 knee, 45 pelvic,
      and 47 spinal examinations were evaluated. RESULTS: Radiological features were
      noted in 45.9% of knee radiographs, 11.1% of pelvic radiographs, and 42.6% of
      spinal radiographs. The findings were reviewed in the light of each patient's
      specific genetic Stickler syndrome subtype. CONCLUSION: The prevalence of
      orthopaedic abnormalities overall in the present series is substantially below
      those published in previous smaller case series. This would support the more
      recent findings of an array of ocular only phenotypes of Stickler syndrome
      described in the literature.

PMID- 29661560
TI  - Observational Prospective Natural History of Patients with Sanfilippo Syndrome
      Type B.
AB  - OBJECTIVE: To evaluate the natural course of disease progression in patients with
      Sanfilippo syndrome type B (mucopolysaccharidosis type IIIB), identify potential
      end points for future therapy trials, and characterize biomarkers related to the
      disease. STUDY DESIGN: A prospective, multicenter study was conducted. Baseline,
      6-month, and 12-month assessments included neurodevelopmental status (Bayley
      Scales of Infant Development, Third edition), adaptive status (Vineland Adaptive
      Behavior Scales, Second Edition), volumetric brain magnetic resonance imaging,
      cerebrospinal fluid heparan sulfate, and urine glycosaminoglycan (GAG)
      measurements. RESULTS: Nineteen patients aged 1.6-31.7 years were enrolled. Over
      12 months, cognition, adaptive behavior, and cortical gray matter volume (GMV)
      declined in most patients. For patients diagnosed at <6 years, although there was
      no overall mean change over 12 months, there were 10%-48%, 3%-66%, and 1%-14%
      decreases in cognitive development quotient score, Vineland Adaptive Behavior
      Scales, Second Edition development quotient score, and cortical GMV in 8/12,
      9/11, and 10/11 patients, respectively. Mean urine GAG and cerebrospinal fluid
      heparan sulfate levels were stable, but patients diagnosed at <6 years (n = 14)
      had higher levels than those >=6 years at diagnosis (n = 4), which was likely
      associated with age as they also were generally younger. CONCLUSIONS: Cognition,
      adaptive behavior, and cortical GMV measures sensitively tracked deterioration in
      patients with mucopolysaccharidosis type IIIB aged <=8.6 years. Biomarkers may
      have prognostic value, but their sensitivity to disease progression requires
      further investigation. These findings should help evaluate enzyme replacement and
      gene therapy agents for this rare, devastating, neurodegenerative disease. TRIAL
      REGISTRATION: ClinicalTrials.gov: NCT01509768.

PMID- 29661562
TI  - Initial Metabolic Profiles Are Associated with 7-Day Survival among Infants Born
      at 22-25 Weeks of Gestation.
AB  - OBJECTIVE: To evaluate the association between early metabolic profiles combined
      with infant characteristics and survival past 7 days of age in infants born at 22
      25 weeks of gestation. STUDY DESIGN: This nested case-control consisted of 465
      singleton live births in California from 2005 to 2011 at 22-25 weeks of
      gestation. All infants had newborn metabolic screening data available. Data
      included linked birth certificate and mother and infant hospital discharge
      records. Mortality was derived from linked death certificates and death discharge
      information. Each death within 7 days was matched to 4 surviving controls by
      gestational age and birth weight z score category, leaving 93 cases and 372
      controls. The association between explanatory variables and 7-day survival was
      modeled via stepwise logistic regression. Infant characteristics, 42 metabolites,
      and 12 metabolite ratios were considered for model inclusion. Model performance
      was assessed via area under the curve. RESULTS: The final model included 1
      characteristic and 11 metabolites. The model demonstrated a strong association
      between metabolic patterns and infant survival (area under the curve [AUC] 0.885,
      95% CI 0.851-0.920). Furthermore, a model with just the selected metabolites
      performed better (AUC 0.879, 95% CI 0.841-0.916) than a model with multiple
      clinical characteristics (AUC 0.685, 95% CI 0.627-0.742). CONCLUSIONS: Use of
      metabolomics significantly strengthens the association with 7-day survival in
      infants born extremely premature. Physicians may be able to use metabolic
      profiles at birth to refine mortality risks and inform postnatal counseling for
      infants born at <26 weeks of gestation.

PMID- 29661563
TI  - Pharmacists in humanitarian crisis settings: Assessing the impact of pharmacist
      delivered home medication management review service to Syrian refugees in Jordan.
AB  - BACKGROUND: Refugees all over the world are facing several health-related
      problems. Chronic diseases among Syrian refugees in Jordan are high. The Home
      Medication Management Review (HMMR) service could be ideal to optimize refugees'
      health management. OBJECTIVES: To assess the impact of the HMMR service on the
      type and frequency of Treatment Related Problems (TRPs) among Syrian refugees
      living in Jordan. METHODS: This prospective randomized single blinded
      intervention-control study was conducted in three main cities in Jordan, between
      May and October 2016. Syrian refugees with chronic conditions were recruited and
      randomized into intervention and control groups. The HMMR service was conducted
      for all patients to identify TRPs at baseline. Data were collected via two home
      visits for all study participants. Clinical pharmacist's recommendations were
      written in a letter format to the physicians managing the patients in the
      intervention group only. Physicians' approved recommendations were conveyed to
      the patients via the pharmacist. Interventions at the patient level were
      delivered by the pharmacist directly. Patients were reassessed for their TRPs and
      satisfaction 3 months after baseline. RESULTS: Syrian refugees (n = 106) were
      recruited with no significant differences between the intervention (n = 53) and
      control groups (n = 53). A total of 1141 TRPs were identified for both groups at
      baseline, with a mean number of 10.8 +/- 4.2 TRPs per patient. At follow-up,
      there was a significant decrease in the number of TRPs among the intervention
      group (P < 0.001, paired sample t-test) but not among the control group (P =
      0.116). Physicians' approval rate of the pharmacist's recommendations was high
      (82.9%), and more than 70.0% of refugees in the intervention group reported high
      satisfaction with the HMMR service. CONCLUSION: Identified TRPs are high amongst
      Syrian refugees living in Jordan. The HMMR service significantly reduced the
      number of TRPs, and was highly accepted by the physicians. Refugees reported high
      satisfaction with this service.

PMID- 29661564
TI  - A new technique for hepatic parenchymal transection using an articulating bipolar
      5 cm radiofrequency device: results from the first 100 procedures.
AB  - BACKGROUND: Parenchymal transection(PT) still remains a challenge in liver
      resection. The outcomes of the first experience of a novel vessel-sealer for
      hepatic transection were assessed. METHODS: A bipolar articulating vessel-sealer
      (Caiman(r), Aesculap Inc., Center Valley, PA) was used in 100 liver resections
      through both open (OLR) and laparoscopic (LLR) approaches. All data were
      prospectively collected into an IRB-approved department database, and clinical,
      surgical and perioperative parameters were analyzed. RESULTS: Fifty patients
      underwent OLR and 50 patients underwent LLR. Eighty hepatectomies were performed
      for malignancy. Median number of tumors was 1, with the largest focus measuring
      an average of 5.1 cm. Forty-nine of the procedures were major liver resections.
      Parenchymal transection time was 29.9 +/- 3.1 min in OLR and 29.9 +/- 3.6 min in
      LLR. Median estimated blood loss was 300 cc (Inter-quartile range (IQR) 100-575
      cc). Median hospital stay was 6 days for open and 3 days for laparoscopic
      procedures. Ninety-day complication rate was 8% without any mortality. Bile leak
      rate was 4%. Staplers were used for parenchymal transection in 16 cases.
      CONCLUSION: This study introduces a new multifunctional device into the
      armamentarium of the liver surgeon. In our experience, this device facilitated
      the parenchymal transection by adding speed and consolidating the amount of
      instrumentation used in liver resection without increasing complications.

PMID- 29661565
TI  - Fetal growth restriction in twins.
AB  - Twin pregnancies are more likely to be affected by fetal growth restriction
      (FGR), preterm birth and perinatal loss. The management of fetal growth
      restriction in multiple pregnancy, particularly where only one fetus is affected
      is complicated by the need to consider the interests of both twins. Selective
      growth restriction in monochorionic (MC) twins is a pathophysiological process
      distinct from FGR in dichorionic (DC) pregnancies and management demands an
      understanding of the monochorionic placental structure and interdependent fetal
      circulations. The introduction of fetal therapy has introduced a range of
      potential interventions for the antenatal management of sFGR including selective
      fetal reduction and laser photocoagulation of the placental communicating
      vessels. This review summarizes up to date evidence on diagnosis, classification
      and management of sFGR and considers research directions likely to be of benefit
      in the future.

PMID- 29661566
TI  - Lichen Planopilaris and Frontal Fibrosing Alopecia as Model Epithelial Stem Cell
      Diseases.
AB  - Inflammation-associated, irreversible damage to epithelial stem cells (eSCs) of
      the hair follicle in their immunologically privileged niche lies at the heart of
      scarring alopecia, which causes permanent difficult-to-treat hair loss. We
      propose that the two most common and closely related forms, lichen planopilaris
      (LPP) and frontal fibrosing alopecia (FFA), provide excellent model diseases for
      studying the biology and pathology of adult human eSCs in an easily accessible
      human mini-organ. Emphasising the critical roles for interferon (IFN)-gamma and
      peroxisome proliferator-activated receptor (PPAR)-gamma-mediated signalling in
      immune privilege (IP) collapse and epithelial-mesenchymal transition (EMT) of
      these eSCs respectively, we argue that these pathways deserve therapeutic
      targeting in the future management of LPP/FFA and other eSC diseases associated
      with IP collapse and EMT.

PMID- 29661561
TI  - Clinically Actionable Hypercholesterolemia and Hypertriglyceridemia in Children
      with Nonalcoholic Fatty Liver Disease.
AB  - OBJECTIVE: To determine the percentage of children with nonalcoholic fatty liver
      disease (NAFLD) in whom intervention for low-density lipoprotein cholesterol or
      triglycerides was indicated based on National Heart, Lung, and Blood Institute
      guidelines. STUDY DESIGN: This multicenter, longitudinal cohort study included
      children with NAFLD enrolled in the National Institute of Diabetes and Digestive
      and Kidney Diseases Nonalcoholic Steatohepatitis Clinical Research Network.
      Fasting lipid profiles were obtained at diagnosis. Standardized dietary
      recommendations were provided. After 1 year, lipid profiles were repeated and
      interpreted according to National Heart, Lung, and Blood Institute Expert Panel
      on Integrated Guidelines for Cardiovascular Health and Risk Reduction. Main
      outcomes were meeting criteria for clinically actionable dyslipidemia at
      baseline, and either achieving lipid goal at follow-up or meeting criteria for
      ongoing intervention. RESULTS: There were 585 participants, with a mean age of
      12.8 years. The prevalence of children warranting intervention for low-density
      lipoprotein cholesterol at baseline was 14%. After 1 year of recommended dietary
      changes, 51% achieved goal low-density lipoprotein cholesterol, 27% qualified for
      enhanced dietary and lifestyle modifications, and 22% met criteria for
      pharmacologic intervention. Elevated triglycerides were more prevalent, with 51%
      meeting criteria for intervention. At 1 year, 25% achieved goal triglycerides
      with diet and lifestyle changes, 38% met criteria for advanced dietary
      modifications, and 37% qualified for antihyperlipidemic medications. CONCLUSIONS:
      More than one-half of children with NAFLD met intervention thresholds for
      dyslipidemia. Based on the burden of clinically relevant dyslipidemia, lipid
      screening in children with NAFLD is warranted. Clinicians caring for children
      with NAFLD should be familiar with lipid management.

PMID- 29661567
TI  - Geriatric traumatic brain injury: An old challenge.

PMID- 29661568
TI  - Cultivated bacterial diversity associated with the carnivorous plant Utricularia
      breviscapa (Lentibulariaceae) from floodplains in Brazil.
AB  - Carnivorous plant species, such as Utricularia spp., capture and digest prey.
      This digestion can occur through the secretion of plant digestive enzymes and/or
      by bacterial digestive enzymes. To comprehend the physiological mechanisms of
      carnivorous plants, it is essential to understand the microbial diversity related
      to these plants. Therefore, in the present study, we isolated and classified
      bacteria from different organs of Utricularia breviscapa (stolons and utricles)
      and from different geographic locations (Sao Paulo and Mato Grosso). We were able
      to build the first bacterium collection for U. breviscapa and study the diversity
      of cultivable bacteria. The results show that U. breviscapa bacterial diversity
      varied according to the geographic isolation site (Sao Paulo and Mato Grosso) but
      not the analyzed organs (utricle and stolon). We reported that six genera were
      common to both sample sites (Sao Paulo and Mato Grosso). These genera have
      previously been reported to be beneficial to plants, as well as related to the
      bioremediation process, showing that these isolates present great
      biotechnological and agricultural potential. This is the first report of an
      Acidobacteria isolated from U. breviscapa. The role of these bacteria inside the
      plant must be further investigated in order to understand their population
      dynamics within the host.

PMID- 29661569
TI  - Analysis of GWAS-linked variants in multiple system atrophy.
AB  - A recent genome-wide association study performed in European population
      identified 4 potentially interesting gene loci of multiple system atrophy (MSA),
      including the EDN1 rs16872704, MAPT rs9303521, FBXO47 rs78523330, and ELOVL7
      rs7715147. Because of the genetic heterogeneity, we aimed to explore the possible
      genetic association between above 4 single nucleotide polymorphisms (SNPs) and
      MSA in Chinese Han population from Mainland China, Taiwan, and Singapore. A total
      of 1847 subjects comprising 906 MSA patients and 941 unrelated healthy controls
      were genotyped by directly sequencing for these SNPs. No significant differences
      in the genotype distributions, minor allele frequency of EDN1 rs16872704, MAPT
      rs9303521, FBXO47 rs78523330, and ELOVL7 rs7715147 between MSA patients and
      healthy controls, and between subtypes of MSA patients (MSA-C and MSA-P), were
      found. In conclusion, we demonstrated that genome-wide association study-linked
      SNPs in Caucasians do not confer a significant risk for MSA in the Chinese
      population.

PMID- 29661570
TI  - Is hip strengthening the best treatment option for females with patellofemoral
      pain? A randomized controlled trial of three different types of exercises.
AB  - OBJECTIVE: To evaluate the effect of three types of exercise intervention in
      patients with patellofemoral pain and to verify the contributions of each
      intervention to pain control, function, and lower extremity kinematics. METHODS:
      A randomized controlled, single-blinded trial was conducted. Forty women with
      patellofemoral pain were randomly allocated into four groups: hip exercises,
      quadriceps exercises, stretching exercises and a control group (no intervention).
      Pain (using a visual analog scale), function (using the Anterior Knee Pain
      Scale), hip and quadriceps strength (using a handheld isometric dynamometer) and
      measuring lower limb kinematics during step up and down activities were evaluated
      at baseline and 8 weeks post intervention. RESULTS: All treatment groups showed
      significant improvements on pain and Anterior Knee Pain Scale after intervention
      with no statistically significant differences between groups except when compared
      to the control group. Only hip and quadriceps groups demonstrated improvements in
      muscle strength and knee valgus angle during the step activities. CONCLUSION: Hip
      strengthening exercises were not more effective for pain relief and function
      compared to quadriceps or stretching exercises in females with patellofemoral
      pain. Only hip and quadriceps groups were able to decrease the incidence of
      dynamic valgus during step-down activity. This study was approved by Brazilian
      Clinical Trials Registry registration number: RBR-6tc7mj
      (http://www.ensaiosclinicos.gov.br/rg/RBR-6tc7mj/).

PMID- 29661571
TI  - Drug-related homicide in Europe-First review of data and sources.
AB  - BACKGROUND: Drugs can act as facilitators for all types of violence, including
      drug-related homicide (DRH). Addressing this phenomenon is not only of importance
      given the severity of a homicide event and its high costs on society, but also
      because DRH has the potential to act as a valuable indicator or proxy of wider
      drug-related violent crime. However, there appears to be an important gap in
      terms of available European data on DRH. This study aimed to identify relevant
      European data sources on DRH, to assess the role of drugs in national homicide
      data, and to assess these sources and data in terms of monitoring potential.
      METHODS: A critical review was conducted of existing national and international
      homicide data sources. A three-step approach was adopted, including systematic
      searches for data sources and literature, snowballing methods, and contacting
      professionals. RESULTS: Data on DRH is systematically prepared in the Czech
      Republic, Denmark, Finland, Germany, Italy, the Netherlands, Norway, Slovakia,
      Sweden, and the United Kingdom (England, Wales, and Scotland). Available data
      suggests both between- and within country variability in relation to the role of
      drugs in homicide events. Based on these findings, four key obstacles can be
      identified in terms of the current ability to monitor DRH: missing data,
      fragmented data, comparability issues and data quality reservations. CONCLUSION:
      To overcome these obstacles, there is a need for an international monitoring
      system that incorporates DRH. Ideally, the system should employ a single shared
      definition, standardised terminology, one coordinating body, and the use of
      multiple data sources. There are several approaches towards such a system,
      notably expanding the European Homicide Monitor (EHM) framework. Options should
      be explored to incorporate DRH into this existing and growing monitoring system.

PMID- 29661572
TI  - Chemsex and mental health as part of syndemic in gay and bisexual men.
AB  - A commentary is provided on the study reported by Garrett Prestage and his
      colleagues, which examined the relations between mental health states, non
      injection drug use and sexual risk behaviors in a cross-sectional sample of
      3,017Australian gay and bisexual men. We provide a summary of the findings in
      relation to the extant literature on the interconnectedness of these behaviors
      and health states and interpret the findings in this regard, noting both
      strengths and limitations. We couch our commentary in a theory of syndemics for
      considering how these associations may manifest and for informing both research
      and practice. While the data from this investigation posit risk they also point
      to strength and suggest the application of a resilience framework for addressing
      the health needs of gay and bisexual men.

PMID- 29661574
TI  - Letter to the Editor.

PMID- 29661573
TI  - Outcomes following laparoscopic versus open surgery for pediatric inguinal hernia
      repair: Analysis using a national inpatient database in Japan.
AB  - BACKGROUND: This study compared perioperative outcomes between laparoscopic
      surgery (LS) and open surgery (OS) for pediatric inguinal hernia repair, using a
      national inpatient database. METHODS: Using the Diagnosis Procedure Combination
      database in Japan, we compared duration of anesthesia, postoperative
      complications, recurrence, and metachronous hernia (MH) between LS and OS for
      children undergoing inguinal hernia repair from July 2010 to March 2016. We used
      multivariable logistic regression analysis for postoperative complications and
      Cox regression analysis for recurrence. RESULTS: For 75,486 eligible patients (LS
      20,186 vs. OS 55,300), the median follow-up was 815 (381-1350) days in LS and
      1106 (576-1603) days in OS. The duration of anesthesia was significantly longer
      in LS than in OS for unilateral surgery (80 vs. 70min, p<0.001) but shorter for
      bilateral surgery (86 vs. 96min, p<0.001). LS had a lower proportion of MH than
      OS (0.3% vs. 3.4%, p<0.001). There was no significant difference between LS and
      OS in complications (odds ratio: 0.55; 95% confidence interval: 0.22-1.38;
      p=0.20) or recurrence (hazard ratio: 1.24; 95% confidence interval: 0.86-1.79;
      p=0.89). CONCLUSIONS: LS patients had lower proportions of MH than OS patients.
      Complications and recurrence did not differ significantly between LS and OS. TYPE
      OF STUDY: Retrospective study. LEVELS OF EVIDENCE: Level III.

PMID- 29661575
TI  - Outcomes of laparoscopic resection of Meckel's diverticulum are equivalent to
      open laparotomy.
AB  - PURPOSE: Meckel's diverticulum (MD) is a common congenital anomaly caused by
      failure of involution of the omphalomesenteric duct. Enthusiasm for minimally
      invasive surgery (MIS) in children has burgeoned as technologies have advanced,
      but the outcomes of laparoscopic resection in comparison to open laparotomy for
      MD remain poorly defined. We queried a large national database to compare current
      practice patterns and clinical outcomes between surgical approaches for MD in the
      pediatric population. METHODS: The National Surgical Quality Improvement Program
      Pediatric (NSQIP-Ped) database was queried for patients undergoing surgical
      intervention for MD (2011-2014). Patients were stratified by surgical approach.
      Baseline characteristics, intraoperative variables, and perioperative
      complications were compared by univariate analysis using Pearson's chi2 test for
      categorical variables and Kruskall-Wallis test for continuous variables. Primary
      outcomes of interest were length of stay (LOS), rate of readmission, and 30-day
      mortality. Secondary outcomes included operative time, anesthesia time,
      postoperative complications, and rates of reoperation. RESULTS: A total of 148
      cases of MD were identified, of which 73 (49.3%) were initially managed with a
      laparoscopic approach and 75 (50.7%) were managed with an open approach. We found
      a high rate of conversion from laparoscopy to an open approach (20/73 or 27.4%).
      The median age of the laparoscopic group was higher than the open group (8.3 vs.
      2.5years, p<0.001). Operative and anesthesia time, LOS, 30-day mortality, post
      operative complications, and rates of reoperation and readmission were similar
      between groups (all p>0.05). CONCLUSION: Nearly half of all resections for MD in
      children are now approached laparoscopically. This approach has equivalent
      outcomes to traditional open laparotomy. More widespread use of a hybrid approach
      with laparoscopy and exteriorization of the small bowel through an extended port
      site may facilitate avoiding open laparotomy. Routine conversion to open for
      palpation of the MD or segmental small bowel resection should be avoided in the
      absence of compelling intra-operative findings or operative complications. LEVEL
      OF EVIDENCE: Level III (retrospective comparative study).

PMID- 29661577
TI  - What matters in a transferable neural network model for relation classification
      in the biomedical domain?
AB  - A lack of sufficient labeled data often limits the applicability of advanced
      machine learning algorithms to real life problems. However, the efficient use of
      transfer learning (TL) has been shown to be very useful across domains. TL make
      use of valuable knowledge learned in one task (source task), where sufficient
      data is available, in order to improve performance on the task of interest
      (target task). In the biomedical and clinical domain, a lack of sufficient
      training data means that machine learning models cannot be fully exploited. In
      this work, we present two unified recurrent neural models leading to three
      transfer learning frameworks for relation classification tasks. We systematically
      investigate the effectiveness of the proposed frameworks in transferring
      knowledge from a source task to a target task when the characteristics of the
      source data vary, such as similarity or relatedness between the source and target
      tasks, and the size of training data for the source task. Our empirical results
      show that the proposed frameworks, in general, improve the model performance.
      However, these improvements do depend on characteristics of source and target
      tasks. This dependence then finally determine the choice of a particular TL
      framework.

PMID- 29661576
TI  - Treatment of experimental necrotizing enterocolitis with stem cell-derived
      exosomes.
AB  - PURPOSE: Necrotizing enterocolitis (NEC) remains a devastating disease in
      premature infants. We previously showed that four stem cell (SC) types
      equivalently improve experimental NEC. Exosomes are intercellular nanovesicles
      containing RNA, miRNA, DNA, and protein. Because SC therapy faces challenges, our
      aim was to determine if the beneficial effects of SC are achievable with cell
      free exosomes. METHODS: Exosomes from four SC types were compared: (1) amniotic
      fluid-derived mesenchymal SC (AF-MSC); (2) bone marrow-derived MSC (BM-MSC); (3)
      amniotic fluid-derived neural SC (AF-NSC); and (4) neonatal enteric NSC (E-NSC).
      Rat pups exposed to NEC received a varying concentration of a single type of
      exosome with control pups receiving PBS only. Intestinal damage was graded
      histologically. RESULTS: The incidence of NEC was 0% in unstressed pups and 60.7%
      in control pups subjected to NEC. Exosomes (4.0*108) reduced NEC incidence to: AF
      MSC 25.0%; BM-MSC 23.1%; AF-NSC 11.1%; E-NSC 27.3%. When administered at a
      concentration of at least 4.0*108, all groups demonstrated a significant
      reduction in NEC compared to untreated pups. At this minimum concentration, there
      was no difference in treatment efficacy between exosomes and the SC from which
      they were derived. CONCLUSION: Stem cell-derived exosomes reduce the incidence
      and severity of experimental NEC as effectively as the stem cells from which they
      are derived, supporting the potential for novel cell-free exosome therapy for
      NEC. TYPE OF STUDY: Basic science.

PMID- 29661578
TI  - Optimization of the etch-and-rinse technique: New perspectives to improve resin
      dentin bonding and hybrid layer integrity by reducing residual water using
      dimethyl sulfoxide pretreatments.
AB  - OBJECTIVE: To determine whether bonding effectiveness and hybrid layer integrity
      on acid-etched dehydrated dentin would be comparable to the conventional wet
      bonding technique through new dentin biomodification approaches using dimethyl
      sulfoxide (DMSO). METHODS: Etched dentin surfaces from extracted sound molars
      were randomly bonded in wet or dry conditions (30s air drying) with DMSO/ethanol
      or DMSO/H2O as pretreatments using a simplified (Scotchbond Universal Adhesive,
      3M ESPE: SU) and a multi-step (Adper Scotchbond Multi-Purpose, 3M ESPE: SBMP)
      etch-and-rinse adhesives. Untreated dentin surfaces served as control. Bonded
      teeth (n=8) were stored in distilled water for 24h and sectioned into resin
      dentin beams (0.8mm2) for microtensile bond strength test and quantitative
      interfacial nanoleakage analysis (n=8) under SEM. Additional teeth (n=2) were
      prepared for micropermeability assessment by CFLSM under simulated pulpar
      pressure (20cm H2O) using 5mM fluorescein as a tracer. Microtensile data was
      analyzed by 3-way ANOVA followed by Tukey Test and nanoleakage by Kruskal-Wallis
      and Dunn-Bonferroni multiple comparison test (alpha=0.05). RESULTS: While dry
      bonding of SBMP produced significantly lower bond strengths than wet-bonding
      (p<0.05), DMSO/H2O and DMSO/ethanol produced significantly higher bond strengths
      for SBMP irrespective of dentin condition (p<0.05). SU presented significantly
      higher nanoleakage levels (p<0.05) and micropermeability than SBMP. Improvement
      in hybrid layer integrity occurred for SBMP and SU for both pretreatments, albeit
      most pronouncedly for DMSO/ethanol regardless of dentin moisture. CONCLUSION:
      DMSO pretreatments may be used as a new suitable strategy to improve bonding of
      water-based adhesives to demineralized air-dried dentin beyond conventional wet
      bonding. Less porous resin-dentin interfaces with higher bond strengths on air
      dried etched dentin were achieved; nonetheless, overall efficiency varied
      according to DMSO's co-solvent and adhesive type. CLINICAL SIGNIFICANCE: DMSO
      pretreatments permit etched dentin to be air-dried before hybridization
      facilitating residual water removal and thus improving bonding effectiveness.
      This challenges the current paradigm of wet-bonding requirement for the etch-and
      rinse approach creating new possibilities to enhance the clinical longevity of
      resin-dentin interfaces.

PMID- 29661579
TI  - Effect of acid etching on tridimensional microstructure of etchable CAD/CAM
      materials.
AB  - OBJECTIVE: Evaluate if etching protocols affect superficial/internal
      microstructural integrity of CAD/CAM ceramic materials. METHODS: Sixty blocks
      (3*3*3mm) of IPS/Empress-LEU, IPS/e.max-LDC (Ivoclar-Vivadent) and Enamic-PIC
      (VITA) were used. Lateral surfaces from each block were isolated with Teflon
      strip and petroleum jelly to keep them untouched. Specimens were distributed into
      6 groups (n=10): 1. no treatment (C); 2. hydrofluoric acid (HF) 5%, 20s
      (HF5%20s); 3. HF5%60s; 4. HF10%20s; 5. HF10%60s; 6. Monobond Etch&Prime (MBEP).
      Surface roughness (Sa) and 3D profile were obtained using a confocal-laser
      optical-microscope (LEXT OLS 4000, Olympus), while element ratios (Si/K for LEU
      and LDC; Si/C for PIC) were recorded using energy dispersive spectroscopy (EDS).
      Superior (treated) and lateral (non-treated) surfaces were analyzed using
      scanning electron microscopy (SEM) (JSM 5600 LV, JEOL). Etching depth was
      measured on lateral surfaces. Data were submitted to ANOVA-One-Way and Tukey test
      (alpha=0.05). RESULTS: For LEU, only HF10% treatments produced statistically
      different roughness values and Si/K ratios compared to C group. Regarding LDC and
      PIC, groups HF5%60s and HF10% showed higher roughness values than C group. In the
      case of PIC, all treatments (except MBEP) produced lower Si/C ratios than C
      group. All treatments (except MBEP) produced higher etching depth values than C
      group for all materials, being HF10%60s the highest (LEU:403.2+/-11.4MUm;
      LDC:617.4+/-75.7; PIC:291.6+/-6.5MUm). HF10% produced more aggressive etching
      morphology patterns on superior and lateral surfaces (SEM). Treatments MBEP and
      HF5%20s, produced the least aggressive structural alterations. Acid etching
      produces superficial and internal alterations on ceramics' structural
      configuration. SIGNIFICANCE: Aggressive etching protocols of glass-ceramics may
      cause internal material loss, consequently, milder etching is recommended to
      treat those materials before adhesion procedures.

PMID- 29661580
TI  - Preparation and characterization of Bis-GMA-free dental composites with
      dimethacrylate monomer derived from 9,9-Bis[4-(2-hydroxyethoxy)phenyl]fluorene.
AB  - OBJECTIVE: Synthesize a new BPA-free monomer for use in methacrylate-based
      materials and evaluate critical properties of resin and composite materials based
      on the monomer. METHODS: Bis-EFMA was synthesized through reaction between 9,9
      bis[4-(2-hydroxyethoxy)-phenyl]fluorene and 2-(methacryloyloxy)ethyl isocyanate.
      Experimental Bis-EFMA-based resin (Bis-EFMA/TEGDMA=50/50, wt./wt.) and composite
      were prepared. Critical properties were investigated according to standard or
      referenced methods Bis-GMA/TEGDMA (50/50, wt./wt.) resin system, Bis-GMA-based
      composite and 3M ESPE FiltekTM Z250 were used as controls. RESULTS: FT-IR and 1H
      NMR spectra confirmed the structure of Bis-EFMA monomer. Cured resin materials:
      Bis-EFMA-based and Bis-GMA-based resins had nearly the same degree of conversion
      (p>0.05); Bis-EFMA-based resin had significantly lower shrinkage, water sorption
      and solubility, and cytotoxicity than Bis-GMA-based resin (p<0.05); flexural
      properties of Bis-EFMA-based resin were all higher than those of Bis-GMA-based
      resin (p<0.05). Cured composite materials: There was no significant difference in
      conversion (p>0.05); Bis-EFMA-based composite had significantly lower shrinkage
      and solubility (p<0.05); water sorption of Bis-EFMA-based composite and Z250 were
      similar (p>0.05), but lower compared to Bis-GMA-based composite (p<0.05); Bis
      EFMA-based composite had the deepest curing depth (p<0.05); Before water
      immersion, there was no significant difference in flexural strength between Bis
      EFMA-based composite and each control composite (p>0.05), while FS became lower
      than that of Z250 (p<0.05), but higher than that of Bis-GMA-based composite
      (p<0.05) after water immersion; Flexural modulus of Bis-EFMA-based composite and
      Z250 were nearly the same (p>0.05), higher than that of Bis-GMA-based composite
      (p<0.05); Bis-EFMA-based composite showed less cytotoxicity than Bis-GMA-based
      composite and Z250 (p<0.05). SIGNIFICANCE: Bis-EFMA has potential as a substitute
      for Bis-GMA to prepare Bis-GMA-free dental composites.

PMID- 29661581
TI  - Typhoid vaccines: WHO position paper, March 2018 - Recommendations.
AB  - This article presented the World Health Organization's (WHO) recommendations on
      the use of Typhoid vaccines excerpted from the Typhoid vaccines: WHO position
      paper - March 2018 published in the Weekly Epidemiological Record (World Health
      Organization, 2018) [1]. This position paper replaces the 2008 WHO position paper
      on typhoid vaccines (WHO, 2008) [2]. It re-emphasizes the importance of
      vaccination to control typhoid fever and presents the WHO recommendations on the
      use of a new generation of typhoid conjugate vaccines. 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 tables. 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 cholera vaccines were discussed by the Strategic
      Advisory Group of Experts (SAGE) in October 2017; evidence presented at these
      meetings can be accessed at:
      http://www.who.int/immunization/sage/meetings/2017/October/presentations_backgrou
      d_docs/en/.

PMID- 29661582
TI  - Parents' preferences for interventions to improve childhood immunization uptake
      in northern Nigeria.
AB  - BACKGROUND: Routine childhood immunization coverage has been low in northern
      Nigeria. While local authorities and international partners have been working
      hard to improve coverage, population preferences for interventions have not been
      documented. This study aimed to understand parents' preferences and identify
      possible interventions to improve uptake of childhood immunization. METHODS:
      Preferences for immunization interventions were elicited using a best-worst
      scaling (BWS) instrument among parents with children under five. We explored the
      value of six program attributes (each varying across three levels) identified
      through a literature review and engagement with local stakeholders. In each of 18
      hypothetical programs identified through a main effect orthogonal design,
      respondents selected the best and worst attributes that may facilitate
      vaccination of children. Assuming sequential best-worst responses, we used
      conditional logit to estimate preferences. We employed latent class analysis
      (LCA) to categorize and examine respondents' preferences across interventions.
      RESULTS: 97 men and 101 women in 198 households were surveyed. The most preferred
      level for each attribute included door-to-door vaccinations, free food
      supplements, bundling with nutritional support programs, involvement of religious
      leaders, information dissemination through media campaigns, and strengthening of
      health services by the government. Three types of preferences were recognized in
      the LCA. The value-driven group (14%) characterized by youngest age,
      predominantly female, and lower education perceived bundled services with food
      and nutritional programs as the most important feature of an intervention.
      Convenience and information seekers (28%) characterized by oldest age and the
      lowest employment preferred door-to-door vaccinations and media campaigns. The
      remaining complacent group (58%), characterized by highest education and highest
      employment, did not show strong preferences to any intervention compared to the
      other two groups. CONCLUSIONS: Routine immunization programs should consider
      joining forces with food and nutritional programs to improve vaccination uptake.
      Incorporating door-to-door visits and media campaigns to target older and
      unemployed populations may increase childhood immunization uptake in northern
      Nigeria.

PMID- 29661583
TI  - Back to the future - Is the drug repositioning concept applicable to vaccines?

PMID- 29661584
TI  - Strategies for increasing uptake of vaccination in pregnancy in high-income
      countries: A systematic review.
AB  - INTRODUCTION: Vaccination in pregnancy is an effective method to protect against
      disease for the pregnant woman, foetus and new born infant. In England, it is
      recommended that pregnant women are vaccinated against pertussis and influenza.
      Improvement in the uptake of both pertussis and influenza vaccination among
      pregnant women is needed to prevent morbidity and mortality for both the pregnant
      women and unborn child. AIM: To identify effective strategies in increasing the
      uptake of vaccination in pregnancy in high-income countries and to make
      recommendations for England. METHODS: A systematic review of peer reviewed
      literature was conducted using a keyword search strategy applied across six
      databases (Medline, Embase, PsychInfo, PubMed, CINAHL and Web of Science).
      Articles were screened against an inclusion and exclusion criteria and papers
      included within the review were quality assessed. RESULTS AND CONCLUSIONS: Twenty
      two articles were included in the review. The majority of the papers included
      were conducted in the USA and looked at strategies to increase influenza
      vaccination in pregnancy. There is limited high quality evidence for strategies
      in high-income countries to increase coverage of pertussis and influenza
      vaccination in pregnancy. A number of strategies have been found to be effective;
      reminders about vaccination on antenatal healthcare records, midwives providing
      vaccination, and education and information provision for healthcare staff and
      patients. Future interventions to increase vaccination in pregnancy should be
      evaluated to ensure efficacy and to contribute to the evidence base.

PMID- 29661585
TI  - Effectiveness of influenza vaccination for children in Japan: Four-year
      observational study using a large-scale claims database.
AB  - BACKGROUND: To date, few large-scale comparative effectiveness studies of
      influenza vaccination have been conducted in Japan, since marketing authorization
      for influenza vaccines in Japan has been granted based only on the results of
      seroconversion and safety in small-sized populations in clinical trial phases not
      on the vaccine effectiveness. We evaluated the clinical effectiveness of
      influenza vaccination for children aged 1-15 years in Japan throughout four
      influenza seasons from 2010 to 2014 in the real world setting. METHODS: We
      conducted a cohort study using a large-scale claims database for employee health
      care insurance plans covering more than 3 million people, including enrollees and
      their dependents. Vaccination status was identified using plan records for the
      influenza vaccination subsidies. The effectiveness of influenza vaccination in
      preventing influenza and its complications was evaluated. To control confounding
      related to influenza vaccination, odds ratios (OR) were calculated by applying a
      doubly robust method using the propensity score for vaccination. RESULTS: Total
      study population throughout the four consecutive influenza seasons was over
      116,000. Vaccination rate was higher in younger children and in the recent
      influenza seasons. Throughout the four seasons, the estimated ORs for influenza
      onset were statistically significant and ranged from 0.797 to 0.894 after doubly
      robust adjustment. On age stratification, significant ORs were observed in
      younger children. Additionally, ORs for influenza complication outcomes, such as
      pneumonia, hospitalization with influenza and respiratory tract diseases, were
      significantly reduced, except for hospitalization with influenza in the 2010/2011
      and 2012/2013 seasons. CONCLUSIONS: We confirmed the clinical effectiveness of
      influenza vaccination in children aged 1-15 years from the 2010/2011 to 2013/2014
      influenza seasons. Influenza vaccine significantly prevented the onset of
      influenza and was effective in reducing its secondary complications.

PMID- 29661586
TI  - Australian rubella serosurvey 2012-2013: On track for elimination?
AB  - BACKGROUND: The World Health Organization has targeted rubella virus for
      elimination regionally. Australia was one of the first countries to implement a
      nationally funded rubella immunisation program, in 1971, and conducts regular
      national rubella serosurveillance studies. We aimed to estimate the
      seroprevalence of rubella-specific IgG antibody in the Australian population by
      age and sex in 2012-2013, to compare the results with three previous serosurveys
      conducted in 1996-1999, 2002 and 2007 and to estimate the effective reproduction
      numbers (Rn). METHODS: This study used 2729 serum and plasma specimens, randomly
      selected from a specimen bank collected in 2012-2013 across Australia. Age groups
      included in the sample ranged from 1 to 49 years. Sera were tested for rubella
      specific IgG-antibody using the Enzygnost anti-rubella IgG enzyme immunoassay and
      classified as positive, negative or equivocal according to rubella-specific IgG
      concentrations of >7 IU/ml, <3 IU/ml and 3-7 IU/ml, respectively. RESULTS: The
      overall proportions seropositive, seronegative and equivocal for rubella-specific
      IgG were 92.1% (95% CI, 91.0-93.2), 6.7% (95% CI, 5.7-7.7) and 1.2% (95% CI, 0.8
      1.6), respectively. The proportion of males seropositive was significantly lower
      than females in the 30-34 (83.1% vs. 96.8%, p = 0.003), 35-39 (86.1% vs. 96.3%, p
      = 0.02) and 40-44 (86.1% vs. 95.7%, p = 0.03) year age groups. Rn for rubella in
      2012-2013 was estimated to be 0.33 (95% CI 0.28-0.39). DISCUSSION: The 2012-2013
      national serosurvey showed levels of rubella-specific IgG seropositivity in the
      Australian population are relatively high with no evidence of decrease compared
      to previous serosurveys conducted in 1996-1999, 2002 and 2007. The lower
      proportion of seropositive males aged 30-44 years likely reflects the initial
      immunisation program targeting females only. To our knowledge this study
      represents the longest period of serosurveillance following introduction of a
      nationally funded rubella immunisation program. The lack of evidence of
      decreasing rubella-specific IgG seropositivity is therefore reassuring for
      Australia and other countries with longstanding high vaccine coverage.

PMID- 29661587
TI  - Medium-term Follow-up of Vascular-targeted Photodynamic Therapy of Localized
      Prostate Cancer Using TOOKAD Soluble WST-11 (Phase II Trials).
AB  - BACKGROUND AND OBJECTIVE: To assess the medium-term tumor control in patients
      with localized prostate cancer (PCa) treated with vascular-targeted photodynamic
      (VTP) therapy with TOOKAD Soluble WST11 (VTP) and to assess the medium-term
      tolerability of the treatment. DESIGN, SETTING, PARTICIPANTS, AND INTERVENTION:
      During the clinical phase II studies, 68 patients were treated with VTP under
      optimal treatment conditions (WST11 at 4mg/kg, light energy at 200J/cm, and a
      light density index >=1) and have been included in a 3.5-yr follow-up. OUTCOME
      MEASUREMENTS AND STATISTICAL ANALYSIS: Post-interventional visits were scheduled
      every 6 mo and conducted as per local standard practice in each study center.
      Cancer-free status was assessed by means of prostate-specific antigen kinetics,
      multiparametric magnetic resonance imaging and/or prostate biopsies. RESULTS AND
      LIMITATIONS: At the end of the 3.5-yr follow-up, overall successful focal
      ablation was achieved for 51 patients (75%). Cancer was identified in the
      untreated lobe in 17 patients (25%). In total, 34 patients (50%) were cancer-free
      in both the prostate lobes. In case of recurrent/persistent malignancy, the
      Gleason score remained consistent or changed at the maximum by one point
      (upgrading by 1 Gleason point to 3+4 for eight patients and 4+3 for two
      patients). There were 64 related adverse events (AEs): 48% were Clavien grade I,
      47% were grade II, and 5% were grade III. There were no Clavien grade IV and V
      AEs. Limitations included small sample size and heterogeneity in the follow-up
      for some centers. CONCLUSIONS: VTP is a safe and efficient treatment and
      represents an alternative option for localized low-risk PCa management over the
      medium term. Precise diagnostic methods and imaging tools are thereby essential
      requirements to ensure safe and complete targeted therapy. PATIENT SUMMARY: In
      this report, we looked at the medium-term outcomes of focal photodynamic therapy
      for early-stage prostate cancer. We found that this form of treatment is
      efficient and might have the potential to become a therapeutic option for low
      risk cancer. Effectiveness depends on precise diagnostic methods, such as
      magnetic resonance imaging and accurate biopsy.

PMID- 29661588
TI  - Impact of Metabolic Diseases, Drugs, and Dietary Factors on Prostate Cancer Risk,
      Recurrence, and Survival: A Systematic Review by the European Association of
      Urology Section of Oncological Urology.
AB  - CONTEXT: To date, established risk factors for prostate cancer (PCa) are limited
      to age, race, family history, and certain genetic polymorphisms. Despite great
      research efforts, available evidence on potentially modifiable risk factors is
      conflicting. Moreover, most studies on PCa risk factors did not consider the
      impact of prostate-specific antigen (PSA) testing on PCa diagnosis. OBJECTIVE: To
      provide a detailed overview of the latest evidence on the role of metabolic
      diseases, drugs, and dietary factors for risk of PCa incidence, recurrence, and
      survival in men exposed to PSA testing. EVIDENCE ACQUISITION: A systematic review
      of the English-language literature was performed using the MEDLINE, Cochrane
      Central Register of Controlled Trials, and Web of Science databases according to
      the Preferred Reporting Items for Systematic Reviews and Meta-analyses
      recommendations. Randomized, case-control, or cohort studies published during the
      periods 2008-2017 (on drugs and metabolic diseases) and 2003-2017 (on dietary
      factors), with extensive follow-up (>=8-10yr for studies on PCa risk; >=2-5yr for
      studies on PCa recurrence, progression, and survival, depending on the review
      subtopic) and adjusting of the analyses, beyond established risk factors, for
      either rate of PSA testing (for risk analyses) or PCa stage and primary treatment
      (for survival analyses), were eligible for inclusion. EVIDENCE SYNTHESIS:
      Overall, 39 reports from 22 observational studies were included. Studies were
      heterogeneous regarding definitions of exposure or outcomes, length of follow-up,
      risk of bias, and confounding. For some risk factors, evidence was insufficient
      to assess potential effects, while for others there was no evidence of an effect.
      For selected risk factors, namely metformin, aspirin and statin use, diabetes,
      obesity, and specific dietary intakes, there was low-quality evidence of modest
      effects on PCa risk. CONCLUSIONS: Current evidence from long-term observational
      studies evaluating the effect of drugs, metabolic diseases, and dietary factors
      for PCa risk considering the impact of PSA testing is still not conclusive.
      Future research is needed to confirm the associations suggested by our review,
      exploring their potential biological explanations and selecting those risk
      factors most likely to trigger effective public health interventions. PATIENT
      SUMMARY: We reviewed the available studies published in the recent literature on
      the potential role of drugs, metabolic diseases, and food and dietary factors for
      the risk of prostate cancer, considering the impact of prostate-specific antigen
      testing on prostate cancer diagnosis. We found that for some factors data are
      currently insufficient to make definitive conclusions, while for others available
      studies seem to indicate an effect on the risk of prostate cancer.

PMID- 29661589
TI  - Challenges and research progress of the use of mesenchymal stem cells in the
      treatment of ischemic stroke.
AB  - Cerebral Ischemic Stroke (CIS) has become a hot issue in medical research because
      of the diversity of risk factors and the uncertainty of prognosis. In the field
      of regenerative medicine, mesenchymal stem cells (MSCs) have an increasingly
      prominent position due to their advantages of multiple differentiation, low
      immunogenicity and wide application. In the basic and clinical research of CIS,
      there are still some problems to be solved in the treatment of CIS. This paper
      will discuss the progresses and some obstacles of current MSCs for the treatment
      of CIS.

PMID- 29661591
TI  - Respiratory health in Italy.

PMID- 29661590
TI  - Rituximab was effective for acute disseminated encephalomyelitis followed by
      recurrent optic neuritis with anti-myelin oligodendrocyte glycoprotein
      antibodies.
AB  - BACKGROUND: The effect of rituximab on acute disseminated encephalomyelitis
      (ADEM) followed by recurrent optic neuritis (ON) is not yet known. PATIENT: We
      are reporting the case of a 4-year-old Japanese girl who was diagnosed with anti
      myelin oligodendrocyte glycoprotein (MOG) antibody positive ADEM followed by
      recurrent ON. She developed altered mental status, left facial paralysis, left
      paresis, and experienced three episodes of ON. She was treated with rituximab and
      azathioprine (AZA) as prevention for recurrent ON. She relapsed under treatment
      with AZA when CD19 cells reappeared 6 months after the first rituximab infusion.
      However, she has not relapsed since her CD19 count was reduced and kept low with
      rituximab infusion. CONCLUSIONS: It is conceivable that anti-MOG antibodies are
      involved in the pathology of "ADEM followed by recurrent ON," and that the early
      introduction of rituximab, which is involved in the suppression of antibody
      production and has effects on CD20 T lymphocytes, may be a feasible treatment for
      ON. Due to the small number of patients, additional reports on prospectively
      followed patients are needed.

PMID- 29661592
TI  - Monopolar vs. bipolar transurethral resection for non-muscle invasive bladder
      carcinoma: A post-hoc analysis from a randomized controlled trial.
AB  - PURPOSE: Traditionally, transurethral resection of bladder tumors (TURB) is
      performed using monopolar technique. Bipolar resection has been postulated to
      reduce complications. In this study we compare safety and efficacy between
      monopolar TURB (mTURB) and bipolar TURB (bTURB) for patients with primary non
      muscle invasive bladder cancer (NMIBC). MATERIALS AND METHODS: Data were obtained
      from an international multicenter randomized clinical trial that compared the use
      of white light cystoscopy with narrow band imaging-assisted TURB using the
      Olympus system between 2010 and 2014. Main outcomes of interest were operative
      time, perioperative, and postoperative complications, and 12-month recurrence
      free survival. RESULTS: In total, 716 patients were treated for primary NMIBC
      with mTURB (310 patients) or bTURB (406 patients). The use of white light
      cystoscopy or narrow band imaging was equally distributed between the 2 resection
      techniques. Multilevel logistic and linear regression corrected for possible
      confounders showed no significant difference between mTURB and bTURB for
      postoperative complications (OR = 1.76, P = 0.180), postoperative bleeding (OR =
      1.27, P = 0.722), and the combination of intra + postoperative bleeding (OR =
      1.992, P = 0.108). Additionally, no significant difference was found between
      mTURB and bTURB concerning operative time (1.05min. longer for bTURB, P = 0.536),
      intraoperative bleeding requiring intervention (OR:1.38, P=0.809), incidence of
      obturator reflex (OR = 0.93, P = 0.854), and bladder perforation (OR = 3.05, P =
      0.195). In total, 185 patients (25.8%) developed a recurrence (mTURB = 88, bTURB
      = 97). Recurrence-free survival at 12 months in the mTURB and bTURB group was 70%
      and 74% (P = 0.410), respectively. CONCLUSION: Based on these results, bTURB is
      as safe and effective as mTURB in treatment of primary NMIBC. bTURB seems to have
      no evident advantages over mTURB with respect to operation time, perioperative
      and postoperative complication rates, and recurrence rates at 12 months.

PMID- 29661593
TI  - [Diagnostic workup in front of an atypical non hemolytic anemia].
AB  - The most potential causes of "non hemolytic" anemias are iron, folate or vitamin
      B12 deficiencies, severe renal impairment, endocrine diseases, inflammation and
      medullary disorders. In a non-exceptionnal way no cause is found, sometimes
      because of a wrong interpretation of analysis results and sometimes because of a
      little known etiology. The goal of this review is to point out analytical
      difficulties and to remember some rarer etiologies.

PMID- 29661594
TI  - Accidental injuries among older adults: An incidence study.
AB  - BACKGROUND: To date, the majority of studies assessing accidental injuries among
      the elderly have focused on fall injuries, while studies of other mechanisms of
      injuries have been lacking. Therefore, the main objective of this study was to
      investigate all injury-related visits among older adults to an emergency
      department and risk factors for injuries. METHODS: Data were collected on all
      registered visits of adults, >=67 years old, living in the capital of Iceland, to
      the emergency department of Landspitali, the National University Hospital, in
      2011 and 2012. RESULTS: The yearly incidence rate for injuries was 106 per 1000
      adults, >=67 years old. Of all injuries (n = 4,469), falls were the most common
      mechanism of injury (78 per 1000), followed by being struck or hit (12 per 1000)
      and being crushed, cut or pierced (8 per 1000). Other mechanisms of injury, such
      as acute overexertion, foreign body in natural orifice, injuries caused by
      thermal and chemical effect and other and unspecified mechanism were less common
      (8 per 1000). Fractures were the most common consequences of injuries (36 per
      1000). The most frequent place of injury was in or around homes (77 per 1000),
      with men being more likely than women to be injured outside of the home (60 per
      1000 vs. 36 per 1000). CONCLUSION: Results indicate that falls are the main cause
      of accidental injuries, followed by being struck and hit injuries but other
      causes contributed to the rest. Falls constitute a major public health problem
      and fall-related injuries can have a substantial impact on the lives of older
      adults. As life expectancy continues to increase, fall risk is expected to
      increase. Since falls constitute a major impact on the lives of older adults and
      can lead to not only declines in physical activity and functional status, but to
      considerable health care costs, the health care system needs to intervene.

PMID- 29661595
TI  - Excitability of sensory axons in amyotrophic lateral sclerosis.
AB  - OBJECTIVE: To evaluate the excitability of sensory axons in patients with
      amyotrophic lateral sclerosis (ALS). METHODS: Comprehensive sensory nerve
      excitability studies were prospectively performed on 28 sporadic ALS patients,
      compared to age-matched controls. Sensory nerve action potentials were recorded
      from digit 2 following median nerve stimulation at the wrist. Disease severity
      was measured using motor unit number estimation (MUNE), the revised ALS
      Functional Rating Scale (ALSFRS-R) and the MRC scale. RESULTS: There were no
      significant differences in standard and extended measures of nerve excitability
      between ALS patients and controls. These unchanged excitability measures included
      accommodation to long-lasting hyperpolarization and the threshold changes after
      two supramaximal stimuli during the recovery cycle. Excitability parameters did
      not correlate with MUNE, ALSFRS-R, APB MRC scale or disease duration.
      CONCLUSIONS: This cross-sectional study has identified normal axonal membrane
      properties in myelinated sensory axons of ALS patients. Previously described
      sensory abnormalities could be the result of axonal fallout, possibly due to a
      ganglionopathy, or to involvement of central sensory pathways rostral to gracile
      and cuneate nuclei. SIGNIFICANCE: These results demonstrate the absence of
      generalized dysfunction of the membrane properties of sensory axons in ALS in the
      face of substantial deficits in motor function.

PMID- 29661596
TI  - Deep brain stimulation and motor synergies in Parkinson's disease.

PMID- 29661597
TI  - Clinical performance of a dedicated self-apposing stent for the treatment of left
      main stem disease. Results of the left Main AngioplasTy wIth a Self-apposing
      StEnt - the MATISSE study.
AB  - BACKGROUND: In the recent years percutaneous treatment of the left main stem (LM)
      has gained a precise role as a result of consistent scientific evidence vs.
      coronary artery bypass. A self-apposing stent offers an improved adaptation to
      the vessel wall, especially in case of tapered vessels; aim of this study was to
      investigate the role of a novel self-apposing, sirolimus-eluting stent (Stentys,
      France) for the treatment of LM coronary artery disease. METHODS AND RESULTS:
      MATISSE is a retrospective, multicenter registry, which enrolled 151 patients
      treated with the device at 17 international centers. Primary study endpoint was
      the occurrence of major adverse cardiovascular events (MACE), a composite
      endpoint of cardiac death, target lesion revascularization (TLR) and target
      vessel myocardial infarction, at 9months clinical follow-up. Secondary endpoints
      included procedural success, the single determinants of MACE and stent
      thrombosis. Lesions were located in distal LM bifurcation in 84% of the patients.
      Procedural success was achieved in 150 patients. The average follow-up length was
      348+/-52days. MACE occurred in 14 (9.3%) patients with 2 (1.3%) cardiac deaths.
      TLR occurred in 8 patients (5.3%). There were 2 cases of definite stent
      thrombosis, 1 acute and 1 very late. CONCLUSIONS: A self-apposing stent, when
      used for LM PCI in a real world, high risk population, showed good immediate
      procedural results with low rates of adverse events at mid-term follow-up.

PMID- 29661598
TI  - Vitamin D supplementation, bone turnover, and inflammation in HIV-infected
      patients.
AB  - OBJECTIVE: To assess whether vitamin D supplementation could be associated with a
      modification of inflammatory markers and bone turnover in HIV-1-infected
      patients. PATIENTS AND METHODS: Patients who participated in an initial survey in
      2010 and who were followed in the same department were included in a new study in
      2012. Between 2010 and 2012, vitamin D supplementation was offered to patients
      presenting with hypovitaminosis D as per appropriate guidelines. Clinical
      examinations were performed, and fasting blood samples were taken for
      inflammation and bone marker evaluations. RESULTS: Of the 263 patients who
      participated in the 2010 study, 198 were included in the 2012 study.
      Hypovitaminosis D was observed in 47% (36/77) of participants supplemented as per
      appropriate guidelines, in 78% (75/97) of transiently or incompletely
      supplemented participants, and in 71% (17/24) of non-supplemented participants
      (mainly because vitamin D levels in 2010 were normal). No significant correlation
      between vitamin D supplementation and the 2-year inflammation outcome (IL-6 and
      hsCRP) or C-terminal telopeptide levels was observed. However, a decrease in IL6
      levels over the 2 years significantly correlated with reaching a normal vitamin D
      level (OR=0.89 per+1pg/mL IL6 increase, 95% CI=0.81-0.97, P=0.015). CONCLUSIONS:
      Vitamin D supplementation decreases the risk of hypovitaminosis D but does not
      decrease the risk of inflammation nor bone turnover, unless normal 25-OH vitamin
      D levels are reached.

PMID- 29661599
TI  - Transcutaneous nerve stimulation via the tragus: are we really stimulating the
      vagus nerve?

PMID- 29661600
TI  - Directional Deep Brain Stimulation: First experiences in centers across the
      globe.

PMID- 29661601
TI  - Corrigendum to "Evaluation of Texture Analysis Parameter for Response Prediction
      in Patients with Hepatocellular Carcinoma Undergoing Drug-Eluting Bead
      Transarterial Chemoembolization (DEB-TACE) Using Biphasic Contrast-Enhanced CT
      Image Data Correlation with Liver Perfusion CT" [Academic Radiology 24 (2017):
      1352-1363].

PMID- 29661602
TI  - Automated Breast Ultrasound Interpretation Times: A Reader Performance Study.
AB  - RATIONALE AND OBJECTIVES: This study aimed to determine the average time for
      breast radiologists of varied experience to interpret automated breast ultrasound
      (ABUS) examinations. MATERIALS AND METHODS: A reader performance study was
      conducted on female patients, with ACR BI-RADS 4 breast density classifications
      of C or D, who received both an ABUS screening examination and a digital
      mammogram from 2013 to 2014 at an academic institution. Three faculty breast
      radiologists with varied levels of ABUS experience (advanced, intermediate,
      novice) read all ABUS examinations, with interpretation times and final
      impressions (categorized as "normal" or "abnormal") recorded for each
      examination. RESULTS: Ninety-nine patients were included, with all readers
      demonstrating an average ABUS interpretation time of less than 3 minutes.
      Compared to the other two readers, the intermediate reader had a significantly
      longer mean interpretation time at 2.6 minutes (95% confidence interval 2.4-2.8;
      P < .001). In addition to having the shortest mean interpretation time, the
      novice reader also demonstrated reduced times in subsequent interpretations, with
      a significant decrease in interpretation times of 3.1 seconds (95% confidence
      interval 0.4-5.8) for every 10 ABUS examinations interpreted (P < .05).
      CONCLUSIONS: Overall, mean ABUS interpretation time by radiologists of all
      experience levels was short, at less than 3 minutes per examination, which should
      not deter radiologists from incorporating ABUS examinations into a busy clinical
      environment.

PMID- 29661603
TI  - Insulin-induced skin complication in an anti-insulin antibody positive patient
      with type 2 diabetes.

PMID- 29661604
TI  - Cardiovascular risk assessment in prediabetic patients in a hypertensive
      population: The role of cystatin C.
AB  - BACKGROUND: The aim of our study was to determine whether prediabetes increases
      cardiovascular (CV) risk compared to the non-prediabetic patients in our
      hypertensive population. Once this was achieved, the objective was to identify
      relevant CV prognostic features among prediabetic individuals. METHODS: We
      included hypertensive 1652 patients. The primary outcome was a composite of
      incident CV events: cardiovascular death, stroke, heart failure and myocardial
      infarction. We performed a Cox proportional hazard regression to assess the CV
      risk of prediabetic patients compared to non-prediabetic and to produce a
      survival model in the prediabetic cohort. RESULTS: The risk of developing a CV
      event was higher in the prediabetic cohort than in the non-prediabetic cohort,
      with a hazard ratio (HR) = 1.61, 95% CI 1.01-2.54, p = 0.04. Our Cox proportional
      hazard model selected age (HR = 1.04, 95% CI 1.02-1.07, p < 0.001) and cystatin C
      (HR = 2.4, 95% CI 1.26-4.22, p = 0.01) as the most relevant prognostic features
      in our prediabetic patients. CONCLUSIONS: Prediabetes was associated with an
      increased risk of CV events, when compared with the non-prediabetic patients. Age
      and cystatin C were found as significant risk factors for CV events in the
      prediabetic cohort.

PMID- 29661605
TI  - Effect of alive probiotic on insulin resistance in type 2 diabetes patients:
      Randomized clinical trial.
AB  - BACKGROUND: Probiotics have beneficial effect on obesity related disorders in
      animal models. Despite a large number of animal data, randomized placebo
      controlled trials (RCT) concluded that probiotics have a moderate effect on
      glycemic control-related parameters. However, effect of probiotics on insulin
      resistance are inconsistent. AIM: In a double-blind single center RCT, effect of
      alive multistrain probiotic vs. placebo on insulin resistance in type 2 diabetes
      patient were assessed. METHODS: A total of 53 patients met the criteria for
      inclusion. They were randomly assigned to receive multiprobiotic "Symbiter"
      (concentrated biomass of 14 probiotic bacteria genera Bifidobacterium,
      Lactobacillus, Lactococcus, Propionibacterium) or placebo for 8-weeks
      administered as a sachet formulation. The primary main outcome was the change
      HOMA-IR (homeostasis model assessment-estimated insulin resistance) which
      calculated using Matthews et al.'s equation. Secondary outcomes were the changes
      in glycemic control-related parameters, anthropomorphic variables and cytokines.
      RESULTS: Supplementation with alive multiprobiotic for 8 weeks was associated
      with significant reduction of HOMA-IR from 6.85 +/- 0.76 to 5.13 +/- 0.49 (p =
      0.047), but remained static in the placebo group. With respect to our secondary
      outcomes, HbA1c insignificant decreased by 0.09% (p = 0.383) and 0.24% (p =
      0.068) respectively in placebo and probiotics groups. However, in probiotic
      responders (n = 22, patient with decrease in HOMA-IR) after supplementation a
      significant reduction in HbA1c by 0.39% (p = 0.022) as compared to non-responders
      was observed. In addition, from markers of chronic systemic inflammatory state
      only TNF-alpha and IL-1beta changes significantly after treatment with
      probiotics. CONCLUSION: Probiotic therapies modestly improved insulin resistance
      in patients with type 2 diabetes.

PMID- 29661606
TI  - Potential effect of 2-isopropyl-5-methylphenol (thymol) alone and in combination
      with fluconazole against clinical isolates of Candida albicans, C. glabrata and
      C. krusei.
AB  - Limitations of antifungals used in the treatment of candidiasis, as the
      development of resistant strains, are known by the scientific community. In this
      context, the aim of this study was to investigate the activity of 2-isopropyl-5
      methylphenol (thymol) in combination with fluconazole (FLZ) against clinical
      Candida strains. The antifungal activity of thymol along with FLZ was evaluated
      by the Clinical Laboratory Standards Institute (CLSI) M27-A2 broth microdilution
      method. In addition, synergism was observed for clinical strains of Candida spp.
      with combination of thymol-FLZ evaluated by the chequerboard microdilution
      method. The mean of minimum inhibitory concentration (MIC) values of thymol and
      FLZ were 49.37 and 0.475MUg/ml for C. albicans, 51.25 and 18.80MUg/ml for C.
      glabrata and 70 and 179.20MUg/ml for C. krusei strains, respectively. Thymol in
      combination with FLZ exhibited the synergistic effects against all species of
      Candida tested. FICI values for thymol plus FLZ ranged from 0.366 to 0.607 for C.
      albicans strains, 0.367 to 0.482 for C. glabrata strains, and 0.375 to 0.563 for
      C. krusei strains. No antagonistic activity was seen in the strains tested.
      Thymol was found to have a fungicidal effect on Candida species and a synergistic
      effect when combined with FLZ.

PMID- 29661607
TI  - Catheter-related bloodstream infection due to Rhodotorula mucilaginosa with
      normal serum (1->3)-beta-D-glucan level.
AB  - Rhodotorula species are environmental basidiomycete yeasts that have emerged as a
      cause of fungemia in immunocompromised hosts. The insertion of a central venous
      catheter was identified as a major risk factor for Rhodotorula fungemia. Few
      cases reports have reported (1->3)-beta-D-glucan testing at the onset of
      Rhodotorula mucilaginosa fungemia. We report a case of catheter-related
      bloodstream infection due to R. mucilaginosa. Serum beta-D-glucan level was
      normal at the onset of the bloodstream infection. It took 5 days to culture the
      isolate. The patient's fever persisted after empiric treatment with micafungin,
      and a switch to oral voriconazole immediately resolved the fungemia.

PMID- 29661608
TI  - Modafinil alleviates levodopa-induced excessive nighttime sleepiness and restores
      monoaminergic systems in a nocturnal animal model of Parkinson's disease.
AB  - Treatment with dopaminergic agents result excessive daytime sleepiness (EDS) and
      some studies have shown the benefit of using modafinil for treating excessive
      daytime sleepiness of Parkinson's disease (PD) patient. We investigated whether
      modafinil have ameliorative properties against levodopa induced excessive
      nighttime sleepiness (ENS) in MPTP-treated murine nocturnal PD model. Our EEG
      analyses of whole day recordings revealed that modafinil reduce ENS of this
      nocturnal PD models with levodopa medications. Therefore, we investigated
      whether, modafinil post-treatment followed by MPTP shows any effect on monoamine
      contents of brain and found to robustly increased noradrenaline (NA)
      concentration of MPTP treated mice. Modafinil post-treatment, in neurorestorative
      context (5 days post-lesion) led to increased striatal dopamine (DA)
      concentrations of MPTP-treated mice. Here, we first confirmed that modafinil
      ameliorates levodopa induced excessive sleepiness and restores monoaminergic
      systems. The arousal and anti-parkinsonian effects displayed by modafinil
      indicate that in combination with dopaminergic agents, modafinil co
      administration may be worthwhile in trying to suppress the excessive daytime
      sleepiness and progressive dopaminergic neuron loss in PD.

PMID- 29661609
TI  - Assessing the Effect of an Educational Intervention on Nurses' and Patient Care
      Assistants' Comprehension and Documentation of Functional Ability in Pediatric
      Patients with Sickle Cell Disease.
AB  - PURPOSE: In 2014, the Youth Acute Pain Functional Ability Questionnaire (YAPFAQ)
      was developed to investigate patient's self-rated functional ability during times
      of acute pain in the inpatient clinical setting. Although it has great potential,
      the application of this tool has not been made a standard of care. The purpose of
      this multiple methods study was to determine if, through an educational
      intervention, hospital staff could consistently document the YAPFAQ in children
      with sickle cell disease (SCD) during a vaso-occlusive episode. DESIGN AND
      METHODS: Twenty-two staff members participated in an educational intervention and
      semi-structured group discussions. Pre/post surveys measured knowledge of the
      YAPFAQ before and after the intervention. Group discussions were recorded,
      transcribed verbatim, and analyzed for thematic clusters. Retrospective chart
      reviews of children with SCD were reviewed for YAPFAQ documentation frequency
      before and after the intervention. RESULTS: Staff knowledge of who completes the
      YAPFAQ increased after the intervention, (p<.001). YAPFAQ documentation decreased
      after the intervention, (p<.001). Qualitative analysis identified personal,
      physical, and patient barriers to completing the YAPFAQ and multiple
      recommendations to change the method of documentation in the electronic health
      records (EHR). CONCLUSIONS: Although the staff expressed high interest in
      utilizing the YAPFAQ, application was inhibited by delayed translation to the
      EHR. The YAPFAQ continues to hold high potential for directing nursing care, but
      requires staff investment for clinical practice change. PRACTICAL APPLICATIONS: A
      seamless integration between nursing education and translation through EHR is
      recommended as technology continues to integrate into nursing practice.

PMID- 29661610
TI  - Office-based endoscopic botulinum toxin injection in laryngeal movement
      disorders.
AB  - INTRODUCTION: Botulinum toxin injection is widely used for the treatment of
      laryngeal movement disorders. Electromyography-guided percutaneous injection is
      the technique most commonly used to perform intralaryngeal botulinum toxin
      injection. OBJECTIVE: We describe an endoscopic approach for intralaryngeal
      botulinum toxin injection under local anaesthesia without using electromyography.
      TECHNIQUE: A flexible video-endoscope with an operating channel is used. After
      local anaesthesia of the larynx by instillation of lidocaine, a flexible needle
      is inserted into the operating channel in order to inject the desired dose of
      botulinum toxin into the vocal and/or vestibular folds. CONCLUSION: Endoscopic
      botulinum toxin injection under local anaesthesia is a reliable technique for the
      treatment of laryngeal movement disorders. It can be performed by any
      laryngologist without the need for electromyography. It is easy to perform for
      the operator and comfortable for the patient.

PMID- 29661611
TI  - Nasal polyposis (or chronic olfactory rhinitis).
AB  - The concept of chronic rhinosinusitis with or without polyps is founded on the
      structural and functional unicity of the pituitary mucosa and its united response
      to environmental aggression by allergens, viruses, bacteria, pollution, etc. The
      present review sets this concept against the evo-devo three-nose theory, in which
      nasal polyposis is distinguished as specific to the olfactory nose and in
      particular to the non-olfactory mucosa of the ethmoid, which is considered to be
      not a sinus but rather the skull-base bone harboring the olfactory mucosa. The
      evo-devo approach enables simple and precise positive diagnosis of nasal
      polyposis and its various clinical forms, improves differential diagnosis by
      distinguishing chronic diseases of the respiratory nose and those of the
      paranasal sinuses, hypothesizes an autoimmune origin specifically aimed at
      olfactory system auto-antigens, and supports the surgical concept of nasalization
      against that of functional sinus and ostiomeatal-complex surgery. The ventilation
      function of the sinuses seems minor compared to their production, storage and
      active release of nitric oxide (NO) serving to oxygenate arterial blood in the
      pulmonary alveoli. This respiratory function of the paranasal sinuses may indeed
      be their most important. NO trapped in the ethmoidal spaces also accounts for
      certain radiographic aspects associated with nasal polyposis.

PMID- 29661612
TI  - Hearing, self-motion perception, mobility, and aging.
AB  - Hearing helps us know where we are relative to important events and objects in
      our environment and it allows us to track our changing position dynamically over
      space and time. Auditory cues are used in combination with other sensory inputs
      (visual, vestibular, proprioceptive) to help us perceive our own movements
      through space, known as self-motion perception. Whether we are maintaining
      standing balance, walking, or driving, audition can provide unique and important
      information to help optimize self-motion perception, and consequently to support
      safe mobility. Recent epidemiological and experimental studies have provided
      evidence that hearing loss is associated with greater walking difficulties,
      poorer overall physical functioning, and a significantly increased risk of
      falling in older adults. Importantly, the mechanisms underlying the associations
      between hearing status and mobility are poorly understood. It is also critical to
      consider that age-related hearing loss is often concomitant with declines in
      other sensory, motor, and cognitive functions and that these declines may
      interact, particularly during realistic, everyday tasks. Overall, exploring the
      role of auditory cues and the effects of hearing loss on self-motion perception
      specifically, and mobility more generally, are important to both building
      fundamental knowledge about the perceptual processes underlying the ability to
      perceive our movements through space, as well as to optimizing mobility-related
      interventions for those with hearing loss so that they can function better when
      confronted by everyday, real-world, sensory-motor challenges. The goal of this
      paper is to explore the role of hearing in self-motion perception across a range
      of mobility-related behaviors. First, we briefly review the ways in which
      auditory cues are used to perceive self-motion and how sound inputs affect
      behaviors such as standing balance, walking, and driving. Next, we consider age
      related changes in auditory self-motion perception and the potential consequences
      to performance on mobility-related tasks. We then describe how hearing loss is
      associated with declines in mobility-related abilities and increased adverse
      outcomes such as falls. We describe age-related changes to other sensory and
      cognitive functions and how these may interact with hearing loss in ways that
      affect mobility. Finally, we briefly consider the implications of the hearing
      mobility associations with respect to applied domains such as screening for
      mobility problems and falls risk in those with hearing loss and developing
      interventions and training approaches targeting safe and independent mobility
      throughout the lifespan.

PMID- 29661613
TI  - Functions of CaBP1 and CaBP2 in the peripheral auditory system.
AB  - CaBPs are a family of Ca2+ binding proteins related to calmodulin. Two CaBP
      family members, CaBP1 and CaBP2, are highly expressed in the cochlea. Here, we
      investigated the significance of CaBP1 and CaBP2 for hearing in mice lacking
      expression of these proteins (CaBP1 KO and CaBP2 KO) using auditory brain
      responses (ABRs) and distortion product otoacoustic emissions (DPOAEs). In CaBP1
      KO mice, ABR wave I was larger in amplitude, and shorter in latency and faster in
      decay, suggestive of enhanced synchrony of auditory nerve fibers. This
      interpretation was supported by the greater excitability of CaBP1 KO than WT
      neurons in whole-cell patch clamp recordings of spiral ganglion neurons in
      culture, and normal presynaptic function of CaBP1 KO IHCs. DPOAEs and ABR
      thresholds were normal in 4-week old CaBP1 KO mice, but elevated ABR thresholds
      became evident at 32 kHz at 9 weeks, and at 8 and 16 kHz by 6 months of age. In
      contrast, CaBP2 KO mice exhibited significant ABR threshold elevations at 4 weeks
      of age that became more severe in the mid-frequency range by 9 weeks. Though
      normal at 4 weeks, DPOAEs in CaBP2 KO mice were significantly reduced in the mid
      frequency range by 9 weeks. Our results reveal requirements for CaBP1 and CaBP2
      in the peripheral auditory system and highlight the diverse modes by which CaBPs
      influence sensory processing.

PMID- 29661614
TI  - A fluorescence-based imaging approach to pharmacokinetic analysis of
      intracochlear drug delivery.
AB  - Advances in microelectromechanical systems (MEMS) technologies are enhancing the
      development of intracochlear delivery devices for the treatment of hearing loss
      with emerging pharmacological therapies. Direct intracochlear delivery addresses
      the limitations of systemic and intratympanic delivery. However, optimization of
      delivery parameters for these devices requires pharmacokinetic assessment of the
      spatiotemporal drug distribution inside the cochlea. Robust methods of measuring
      drug concentration in the perilymph have been developed, but lack spatial
      resolution along the tonotopic axis or require complex physiological
      measurements. Here we describe an approach for quantifying distribution of
      fluorescent drug-surrogate probe along the cochlea's sensory epithelium with high
      spatial resolution enabled by confocal fluorescence imaging. Fluorescence from FM
      1-43 FX, a fixable endocytosis marker, was quantified using confocal fluorescence
      imaging of whole mount sections of the organ of Corti from cochleae resected and
      fixed at several time points after intracochlear delivery. Intracochlear delivery
      of FM 1-43 FX near the base of the cochlea produces a base-apex gradient of
      fluorescence in the row of inner hair cells after 1 h post-delivery that is
      consistent with diffusion-limited transport along the scala tympani. By 3 h post
      delivery there is approximately an order of magnitude decrease in peak average
      fluorescence intensity, suggesting FM 1-43 FX clearance from both the perilymph
      and inner hair cells. The increase in fluorescence intensity at 72 h post
      delivery compared to 3 h post-delivery may implicate a potential radial transport
      pathway into the scala media.

PMID- 29661615
TI  - A perspective on brain-behavior relationships and effects of age and hearing
      using speech-in-noise stimuli.
AB  - Understanding speech in background noise is often more difficult for individuals
      who are older and have hearing impairment than for younger, normal-hearing
      individuals. In fact, speech-understanding abilities among older individuals with
      hearing impairment varies greatly. Researchers have hypothesized that some of
      that variability can be explained by how the brain encodes speech signals in the
      presence of noise, and that brain measures may be useful for predicting
      behavioral performance in difficult-to-test patients. In a series of experiments,
      we have explored the effects of age and hearing impairment in both brain and
      behavioral domains with the goal of using brain measures to improve our
      understanding of speech-in-noise difficulties. The behavioral measures examined
      showed effect sizes for hearing impairment that were 6-10 dB larger than the
      effects of age when tested in steady-state noise, whereas electrophysiological
      age effects were similar in magnitude to those of hearing impairment. Both age
      and hearing status influence neural responses to speech as well as speech
      understanding in background noise. These effects can in turn be modulated by
      other factors, such as the characteristics of the background noise itself.
      Finally, the use of electrophysiology to predict performance on receptive speech
      in-noise tasks holds promise, demonstrating root-mean-square prediction errors as
      small as 1-2 dB. An important next step in this field of inquiry is to sample the
      aging and hearing impairment variables continuously (rather than categorically) -
      across the whole lifespan and audiogram - to improve effect estimates.

PMID- 29661616
TI  - Feasibility of Providing Pediatric Neurology Telemedicine Care to Youth with
      Headache.

PMID- 29661617
TI  - Caring for Military Children: Implications for Nurse Practitioners.
AB  - Nearly two million American children belong to a military family. Armed Forces
      families are located in almost every state and around the globe. Military
      children are a unique and at times vulnerable population. Military children and
      adolescents may face significant stressors throughout their lives compared to
      their civilian counterparts. Military families encounter frequent moves and over
      half of these children have encountered at least one parental deployment since
      September 11th, 2001. Civilian health care providers often care for military
      children and adolescents. The purpose of this article is to provide pediatric
      providers with an understanding of the deployment cycle and how it relates to
      childhood development, to discuss common military stressors and their impact on
      the family, and to describe strategies and resources pediatric providers can
      utilize to care for this unique population.

PMID- 29661618
TI  - ?
AB  - Cognitive complications are common after surgery in the elderly, and with an
      increased number of elderly patients undergoing surgery, a potential impact of
      anaesthesia and surgery on long term cognition, and especially dementia would be
      concerning. The question whether anaesthesia and surgery in itself induce
      structural changes in the brain and thereby cognitive deterioration, or reveal a
      preexisting cognitive impairment remains unresolved. Several studies show an
      increased risk of reversible cognitive impairment after surgery in the elderly,
      but the risk of inducing dementia remains speculative. Further studies are needed
      to elucidate this potential association. Meanwhile, elderly frail patients need
      to be closely followed including preoperative cognitive screening, since they are
      at increased risk of cognitive deterioration after surgery and discharge.

PMID- 29661619
TI  - Gastrointestinal stromal tumor as a cause of cancer-associated thrombosis.

PMID- 29661620
TI  - Tolerability, Safety, and Outcomes of Neoadjuvant Chemoradiotherapy With
      Capecitabine for Patients Aged >= 70 Years With Locally Advanced Rectal Cancer.
AB  - INTRODUCTION: In studies of colorectal cancer, the elderly have been frequently
      underrepresented because comorbid conditions and functional status often lead to
      study exclusion. For elderly patients with an indication for neoadjuvant
      chemoradiotherapy (nCRT), physicians usually decide using clinical factors
      whether nCRT should be offered. The aim of the present retrospective study was to
      assess the tolerability of nCRT with capecitabine and the surgical outcomes in
      patients aged >= 70 years with locally advanced rectal cancer. PATIENTS AND
      METHODS: Data from 1372 rectal cancer patients diagnosed from 2002 to 2012 at 4
      Dutch hospitals were used. Patients aged >= 70 years were included if they had
      received nCRT, and their data were analyzed for treatment deviations,
      postoperative complications, mortality, disease-free survival (DFS), and overall
      survival (OS). The data were stratified into 3 age groups (ie, 70-74, 75-79, and
      >= 80 years). RESULTS: We identified 447 patients aged >= 70 years. Of these
      patients, 42 had received nCRT, and 37 (88%) had completed nCRT. Radiation
      dermatitis, fatigue, and diarrhea were reported in 62%, 57%, and 43% of the 42
      patients, respectively. Of the 42 patients, 40 (95%) underwent surgery, 1 patient
      refused resection, and 1 patient died during nCRT of severe mucositis due to
      dihydropyrimidine dehydrogenase deficiency. The postoperative complication rate
      was 30%, and the 30-day mortality rate was 0%. A pathologic complete response was
      found in 7.5%. The 2- and 5-year DFS and OS rates were 58.5% and 40.7% and 81.0%
      and 58.2%, respectively. CONCLUSION: The results of the present multicenter study
      have shown that if selected on clinical factors, nCRT with capecitabine is safe
      and well tolerated in elderly patients. No negative effect on surgical outcome
      was measured, and the beneficial effect (pathologic complete response, DFS, and
      OS) seemed comparable to that for younger age groups. We believe that elderly
      patients should not be excluded from nCRT on the basis of age only.

PMID- 29661621
TI  - Predictive Nomogram for Recurrence of Stage I Colorectal Cancer After Curative
      Resection.
AB  - BACKGROUND: Patients with stage I colorectal cancer (CRC) have excellent
      prognosis after curative surgery. However, approximately 5% to 10% of patients
      experience recurrence and have a poor prognosis. Because the incidence of stage I
      CRC is increasing with active screening programs worldwide, a more accurate and
      easy-to-use predictive tool for recurrence is becoming more important. This study
      aimed to develop a predictive nomogram for recurrence in stage I CRC. PATIENTS
      AND METHODS: A total of 1538 patients who underwent curative surgery for stage I
      CRC were enrolled. Predictive factors for recurrence were determined by
      multivariate Cox regression model and were used to develop a predictive nomogram.
      This model was internally validated, and performance was evaluated through
      calibration plots. RESULTS: The cumulative recurrence rate at 5 years after
      surgery for stage I CRC was 5.3%. In multivariate Cox analysis, independent
      predictors of recurrence were tumor location at rectum, pT2 stage, and presence
      of lymphovascular invasion. The 5-year recurrence rate was significantly
      different depending on the number of risk factors (0.7% for 0, 5.8% for 1, and
      9.7% for >= 2 risk factors). On this basis, a nomogram for recurrence-free
      survival was developed and internally validated. The concordance index of the
      nomogram was 0.71, and the performance was acceptable. CONCLUSION: We developed
      and internally validated a nomogram that can predict postoperative recurrence in
      stage I CRC patients. This nomogram may be used to more accurately stratify the
      risk of recurrence and to perform personalized postoperative surveillance in
      stage I CRC patients.

PMID- 29661623
TI  - Nonventilator hospital-acquired pneumonia: Epidemiology to support prevention
      strategies.

PMID- 29661622
TI  - Rational design and screening of peptide-based inhibitors of heat shock factor 1
      (HSF1).
AB  - Heat shock factor 1 (HSF1) is a stress-responsive transcription factor that
      regulates expression of protein chaperones and cell survival factors. In cancer,
      HSF1 plays a unique role, hijacking the normal stress response to drive a cancer
      specific transcriptional program. These observations suggest that HSF1 inhibitors
      could be promising therapeutics. However, HSF1 is activated through a complex
      mechanism, which involves release of a negative regulatory domain, leucine zipper
      4 (LZ4), from a masked oligomerization domain (LZ1-3), and subsequent binding of
      the oligomer to heat shock elements (HSEs) in HSF1-responsive genes. Recent
      crystal structures have suggested that HSF1 oligomers are held together by
      extensive, buried contact surfaces, making it unclear whether there are any
      possible binding sites for inhibitors. Here, we have rationally designed a series
      of peptide-based molecules based on the LZ4 and LZ1-3 motifs. Using a plate
      based, fluorescence polarization (FP) assay, we identified a minimal region of
      LZ4 that suppresses binding of HSF1 to the HSE. Using this information, we
      converted this peptide into a tracer and used it to understand how binding of LZ4
      to LZ1-3 suppresses HSF1 activation. Together, these results suggest a previously
      unexplored avenue in the development of HSF1 inhibitors. Furthermore, the
      findings highlight how native interactions can inspire the design of inhibitors
      for even the most challenging protein-protein interactions (PPIs).

PMID- 29661624
TI  - Long-term care facility National Healthcare Safety Network enrollment challenges,
      2016.
AB  - The Centers for Medicare & Medicaid Services has a national goal to increase the
      number of long-term care facilities reporting Clostridium difficile infection
      data to the Centers for Disease Control and Prevention. A partnership between the
      Tennessee Department of Health and the quality improvement organization, Qsource,
      helped facilitate successful enrollment into the National Healthcare Safety
      Network for nursing homes in the state of Tennessee.

PMID- 29661625
TI  - Unusual presentation of Middle East respiratory syndrome coronavirus leading to a
      large outbreak in Riyadh during 2017.
AB  - BACKGROUND: The hallmark of Middle East respiratory syndrome coronavirus (MERS
      CoV) disease is the ability to cause major health care-associated nosocomial
      outbreaks with superspreading events leading to massive numbers of cases and
      excessive morbidity and mortality. In this report, we describe a patient who
      presented with acute renal failure requiring hemodialysis and became a MERS-CoV
      superspreader, igniting a recent multihospital outbreak in Riyadh. MATERIAL AND
      RESULTS: Between May 31 and June 15, 2017, 44 cases of MERS-CoV infection were
      reported from 3 simultaneous clusters from 3 health care facilities in Riyadh,
      Saudi Arabia, including 11 fatal cases. Out of the total reported cases, 29 cases
      were reported from King Saud Medical City. The cluster at King Saud Medical City
      was ignited by a single superspreader patient who presented with acute renal
      failure. After 14 hours in the open area of the emergency department and 2
      hemodialysis sessions he was diagnosed with MERS-CoV. One hundred twenty contacts
      who had direct unprotected exposure were screened. Among those contacts, 9 out of
      107 health care workers (5 nurses, 3 physicians, and 1 paramedic) and 7 out of 13
      patients tested positive for MERS-CoV. CONCLUSIONS: This hospital outbreak
      demonstrated the difficulties in diagnosing pneumonia in patients with renal and
      cardiac failure, which leads to delayed suspicion of MERS-CoV and hence delay in
      applying the proper infection control procedures. In MERS-CoV endemic countries
      there is an urgent need for developing rapid point-of-care testing that would
      assist emergency department staff in triaging suspected cases of MERS-CoV to
      ensure timely isolation and management of their primary illness and prevent major
      MERS-CoV outbreaks.

PMID- 29661626
TI  - Influence of an independent quarterly audit on publicly reported vancomycin
      resistant enterocococi bacteremia data in Ontario, Canada.
AB  - BACKGROUND: All Ontario hospitals are mandated to self-report vancomycin
      resistant enterocococi (VRE) bacteremias to Ontario's Ministry of Health and Long
      term Care for public reporting purposes. Independent quarterly audits of publicly
      reported VRE bacteremias between September 2013 and June 2015 were carried out by
      Public Health Ontario. VRE bacteremia case-reporting errors between January 2009
      and August 2013 were identified by a single retrospective audit. METHODS:
      Employing a quasiexperimental pre-post study design, the relative risk of VRE
      bacteremia reporting errors before and after quarterly audits were modeled using
      Poisson regression adjusting for hospital type, case counts reported to the
      Ministry of Health and Long-term Care, and autocorrelation via generalized
      estimating equation. RESULTS: Overall, 24.5% (126 out of 514) of VRE bacteremias
      were reported in error; 114 out of 367 (31%) VRE bacteremias reported before
      quarterly audits and 12 out of 147 (8.1%) reported after audits were found to be
      incorrect. In adjusted analysis, quarterly audits of VRE bacteremias were
      associated with significant reductions in reporting errors when compared with
      before quarterly auditing (relative risk, 0.17; 95% confidence interval, 0.05
      0.63). Risk of reporting errors among community hospitals were greater than acute
      teaching hospitals of the region (relative risk, 4.39; 95% CI, 3.07-5.70).
      CONCLUSIONS: This study found independent quarterly audits of publicly reported
      VRE bacteremias to be associated with significant reductions in reporting errors.
      Public reporting systems should consider adopting routine data audits and
      hospital-targeted training to improve data accuracy.

PMID- 29661627
TI  - Is retained bone debris in cannulated orthopedic instruments sterile after
      autoclaving?
AB  - AIMS: Cannulated surgical instruments may retain biologic debris after routine
      cleaning and sterilization. Residual debris after cleaning is assumed to be
      sterile; however, there is no experimental basis for this assumption. The purpose
      of this study was to determine the sterility of retained biodebris found within
      cannulated surgical instruments after autoclave sterilization. MATERIALS AND
      METHODS: Fifteen cannulated drill bits were used to drill pig scapulae to create
      a plug of bone that was exposed to a mixture of Bacillus cereus, Pseudomonas
      aeruginosa, and methicillin-resistant Staphylococcus aureus for 60, 120, or 180
      minutes prior to sterilization. The drill bits were autoclave sterilized using
      standard settings. The "sterilized" bone cores were then incubated in solution
      and streak-plated on blood agar. RESULTS: All 3 positive controls were positive
      for the experimental bacteria. Two negative controls were positive for
      contaminant bacteria. A B. cereus strain was recovered from 1 of the experimental
      group drill bits in the 180-minute group. Pulsed-field gel electrophoresis
      confirmed that the recovered B. cereus strain was identical to the experimental
      inoculate. CONCLUSION: Retained biodebris in cannulated drills may not be sterile
      after standard autoclave sterilization. In addition, delay of surgical instrument
      reprocessing may increase the risk of resistant contamination.

PMID- 29661628
TI  - Virtual Zika transmission and spread on Twitter.

PMID- 29661629
TI  - A collaborative program to increase adult pneumococcal vaccination rates among a
      high-risk patient population receiving care at urgent care clinics.
AB  - OBJECTIVE: We report a project that utilized pharmacy students to increase
      pneumococcal vaccination rates in patients aged 19-64 years with high-risk
      medical conditions within urgent care clinics. The study also sought to better
      identify the number of patients previously vaccinated for pneumococcal disease. A
      total of 1,178 patients were considered eligible for pneumococcal vaccination
      during the study period, 287 (24.4%) of whom were determined to be previously
      vaccinated through chart assessment or patient interview. Of the remaining 891
      patients, chart documentation of pneumococcal vaccination administered at the
      time of the urgent care visit was present for 96 patients (10.7%) in the
      intervention clinics compared with 6 patients in 2 control clinics who received
      the usual standard of care (P < .0001).

PMID- 29661630
TI  - Rapid diagnostics for bloodstream infections: A primer for infection
      preventionists.
AB  - Accurate and rapid antimicrobial susceptibility testing with pathogen
      identification in bloodstream infections is critical to life results for early
      sepsis intervention. Advancements in rapid diagnostics have shortened the time to
      results from days to hours and have had positive effects on clinical outcomes and
      on efforts to combat antimicrobial resistance when paired with robust
      antimicrobial stewardship programs. This article provides infection
      preventionists with a working knowledge of available rapid diagnostics for
      bloodstream infections.

PMID- 29661631
TI  - Chlorhexidine-containing dressings in the prevention of central venous catheter
      related bloodstream infections: A cost and resource utilization analysis.
AB  - BACKGROUND: A recent study reported a reduction in probable/definite central
      venous catheter (CVC)-related bloodstream infections (CRBSIs) in neutropenic high
      risk patients using CVC dressings with a chlorhexidine-containing gel pad.
      METHODS: Based on published data, a health-economic analysis was performed to
      analyze the economic effect of using CVC dressings with a chlorhexidine
      containing gel pad compared to non-chlorhexidine control dressings. A micro
      costing approach was used to determine CRBSI-related direct treatment cost
      factors. RESULTS: Between February 2012 and September 2014, 356 patients (178
      patients in both groups) were analyzed. Distribution of probable and definite
      CRBSI in the chlorhexidine group and control group were 12 (7%) vs 18 (10%) and 9
      (5%) vs 21 (12%), respectively (P = .011). Median overall length of stay (25 vs
      27.5 days; P = .630) and days on treatment with antibacterials (10 vs 12 days; P
      = .140) were similar between the chlorhexidine and control groups. The most
      important cost driver in both groups was treatment on general ward (?4275 [US$
      5173], interquartile range [IQR]: ?592 - ?6504 [US$ 716 - US$ 7871] vs ?4560 [US$
      5518], IQR: ?1227 - ?8567 [US$ 1485 - US$ 10,367]; P = .120), resulting in median
      overall direct treatment costs of ?13,881 (US$ 16,798) [IQR: ?10,922 - ?25,457
      (US$ 13,217 - US$ 30,807) vs ?13,929 [US$ 16,856] [IQR: ?11,295 - ?23,561 (US$
      13,669 - US$ 28,512); P = .640]). CONCLUSION: Our study shows similar results in
      overall direct treatment costs, meaning that higher acquisition costs of
      chlorhexidine-containing dressings did not translate into higher costs. Expenses
      were primarily outweighed by a lower rate of probable/definite CRBSI and reduced
      associated costs.

PMID- 29661632
TI  - Environmental effectiveness of pulsed-xenon light in the operating room.
AB  - BACKGROUND: Manual cleaning and disinfection of the operating room (OR)
      environment may be inadequate due to human error. No-touch technologies, such as
      pulsed-xenon ultraviolet light (PX-UV), can be used as an adjunct to manual
      cleaning processes to reduce surface contamination in the OR. This article
      reports the cumulative results from 23 hospitals across the United States that
      performed microbiologic validation of PX-UV disinfection after manual cleaning.
      METHODS: We obtained samples from 732 high-touch surfaces in 136 ORs at 23
      hospitals, after manual terminal cleaning, and again after PX-UV disinfection (n
      = 1464 surface samples). Samples were enumerated after incubation, and the
      results are reported as total colony-forming units (CFU). RESULTS: The average
      CFU after manual cleaning ranged from 5.8 to 34.37, and after PX-UV, from 0.69 to
      6.43. With manual cleaning alone, 67% of surfaces were still positive for CFUs;
      after PX-UV disinfection, that number decreased to 38% of all sampled surfaces-a
      44% reduction. When comparing manual cleaning to PX-UV, the reduction in CFU
      count was statistically significant. CONCLUSION: When used after the manual
      cleaning process, the PX-UV device significantly reduced contamination on high
      touch surfaces in the OR.

PMID- 29661633
TI  - Managing social media rumors and misinformation during outbreaks.

PMID- 29661634
TI  - Assessing patient risk of central line-associated bacteremia via machine
      learning.
AB  - BACKGROUND: Central line-associated bloodstream infections (CLABSIs) contribute
      to increased morbidity, length of hospital stay, and cost. Despite progress in
      understanding the risk factors, there remains a need to accurately predict the
      risk of CLABSIs and, in real time, prevent them from occurring. METHODS: A
      predictive model was developed using retrospective data from a large academic
      healthcare system. Models were developed with machine learning via construction
      of random forests using validated input variables. RESULTS: Fifteen variables
      accounted for the most significant effect on CLABSI prediction based on a
      retrospective study of 70,218 unique patient encounters between January 1, 2013,
      and May 31, 2016. The area under the receiver operating characteristic curve for
      the best-performing model was 0.82 in production. DISCUSSION: This model has
      multiple applications for resource allocation for CLABSI prevention, including
      serving as a tool to target patients at highest risk for potentially cost
      effective but otherwise time-limited interventions. CONCLUSIONS: Machine learning
      can be used to develop accurate models to predict the risk of CLABSI in real time
      prior to the development of infection.

PMID- 29661636
TI  - Tackling malaria transmission in sub-Saharan Africa.

PMID- 29661635
TI  - Assessment of community-level effects of intermittent preventive treatment for
      malaria in schoolchildren in Jinja, Uganda (START-IPT trial): a cluster
      randomised trial.
AB  - BACKGROUND: Intermittent preventive treatment (IPT) is a well established malaria
      control intervention. Evidence that delivering IPT to schoolchildren could
      provide community-level benefits is limited. We did a cluster-randomised
      controlled trial to assess the effect of IPT of primary schoolchildren with
      dihydroartemisinin-piperaquine (DP) on indicators of malaria transmission in the
      community, in Jinja, Uganda. METHODS: We included 84 clusters, each comprising
      one primary school and the 100 closest available households. The clusters were
      randomly assigned 1:1 to receive IPT with DP or standard care (control) by
      restricted randomisation to ensure balance by geography and school type. Children
      in intervention schools received IPT monthly for up to six rounds (June to
      December, 2014). We did cross-sectional community surveys in randomly selected
      households at baseline and in January to April, 2015, during which we measured
      participants' temperatures and obtained finger-prick blood smears for measurement
      of parasite prevalence by microscopy. We also did entomological surveys 1 night
      per month in households from 20 randomly selected IPT and 20 control clusters.
      The primary trial outcome was parasite prevalence in the final community survey.
      The primary entomological survey outcome was the annual entomological inoculation
      rate (aEIR) from July, 2014, to April, 2015. This trial is registered at
      ClinicalTrials.gov, number NCT02009215. FINDINGS: Among 23 280 students
      registered in the 42 intervention schools, 10 079 (43%) aged 5-20 years were
      enrolled and received at least one dose of DP. 9286 (92%) of 10 079 received at
      least one full course of DP (three doses). Community-level parasite prevalence
      was lower in the intervention clusters than in the control clusters (19% vs 23%,
      adjusted risk ratio 0.85, 95% CI 0.73-1.00, p=0.05). The aEIR was lower in the
      intervention group than in the control group, but not significantly so (10.1 vs
      15.2 infective bites per person, adjusted incidence rate ratio 0.80, 95% CI 0.36
      1.80, p=0.59). INTERPRETATION: IPT of schoolchildren with DP might have a
      positive effect on community-level malaria indicators and be operationally
      feasible. Studies with greater IPT coverage are needed. FUNDING: UK Medical
      Research Council, UK Department for International Development, and Wellcome
      Trust.

PMID- 29661637
TI  - [Epidermolytic palmoplantar keratoderma of Vorner].

PMID- 29661638
TI  - [Anetoderma secondary to molluscum contagiosum].

PMID- 29661639
TI  - Age of patient at the extraction of the third molar.
AB  - The purpose of this study was to assess the age of patients at the time of
      extraction of third molars. Our data included all routine and surgical
      extractions of third molars (n=8199 teeth) performed by general and specialist
      dentists of the public oral health services of the city of Helsinki over the
      period 2013-2014. Measurements included patient's age, gender, the identified
      third molar, the type of anaesthesia, the method of extraction, and the diagnosis
      at extraction. Patients' ages ranged from 10 to 99years. We found significant
      differences between younger and older age groups: third molar extractions
      occurred more often for women than for men below the age of 30years (P<0.001) and
      vice versa for patients older than 30. Extractions were more prevalent for the
      upper jaw (P<0.001), and surgical extractions were more common than routine
      extractions (P<0.001) below the age of 40years, but the corresponding prevalences
      reversed after the age of 40years. Diagnoses at extraction differed between
      younger and older patients. We conclude that the treatment pattern of third
      molars at public health services varies greatly over a lifetime, and that a
      greater variety exists than had been reported previously from oral and
      maxillofacial units.

PMID- 29661640
TI  - Corrigendum to "Photosensitized rose bengal induced phototoxicity on human
      melanoma cell line under natural sunlight exposure" [J. Photochem. Photobiol. B
      Biol. 156(March 2016) 87-99].

PMID- 29661641
TI  - Targeted muscle reinnervation for pain control in an elective transradial
      amputation.

PMID- 29661642
TI  - An Abstinence and Safer Sex Intervention for Adolescents Attending the Public
      Sexually Transmitted Infection Clinic in Singapore.
AB  - PURPOSE: The objective of this study was to evaluate the efficacy of a behavioral
      intervention in increasing secondary abstinence and safer sex among
      heterosexually active adolescents aged 16-19 years. METHODS: This was a
      randomized controlled trial conducted at the only national sexually transmitted
      infection clinic in Singapore. The intervention focused on information giving,
      motivation, and skills building to abstain or practice safer sex. The outcome
      measures were self-reported secondary abstinence, consistent condom use, and
      keeping to one partner in the past 6 months over a 12-month period. We recruited
      688 adolescents, with 337 participants receiving intervention and 351 receiving
      standard care (control). RESULTS: At the 12-month follow-up, 187 (56%)
      intervention participants and 189 (54%) control participants were retained. Over
      the 12-month period, the intervention had a significant effect on secondary
      abstinence in adolescent boys (42% vs. 27%, adjusted risk ratio [aRR] 1.80, 95%
      confidence interval [CI] 1.29-2.34) but not in adolescent girls (21% vs. 24%, aRR
      1.10, 95% CI .68-1.66). Consistent condom use was higher among intervention
      adolescent girls than control adolescent girls (40% vs. 20%, aRR 2.01, 95% CI
      1.32-2.82), but this effect was not evident in adolescent boys (51% vs. 43%, aRR
      1.27, 95% CI .78-1.88). Intervention effect on keeping to one partner was evident
      in both adolescent boys (76% vs. 45%, aRR 1.35, 95% CI 1.06-1.50) and adolescent
      girls (79% vs. 65%, aRR 1.20, 95% CI 1.02-1.23). CONCLUSIONS: An intervention
      targeting adolescents in a clinical care setting did achieve an increase in
      secondary abstinence in adolescent boys, consistent condom use in adolescent
      girls, and keeping to one partner in both genders at 1-year assessment.

PMID- 29661643
TI  - Muscle ultrasound elastography and MRI in preschool children with Duchenne
      muscular dystrophy.
AB  - The aim of this study was to determine muscle tissue elasticity, measured with
      shear-wave elastography, in selected lower limb muscles of patients affected by
      Duchenne muscular dystrophy (DMD) and to correlate the values obtained with those
      recorded in healthy children and with muscle magnetic resonance imaging (MRI)
      data from the same DMD children, specifically the pattern on T1-weighted (w) and
      short-tau inversion recovery (STIR) sequences. Five preschool DMD children and
      five age-matched healthy children were studied with shear-wave elastography. In
      the DMD children, muscle stiffness was moderately higher compared with the muscle
      stiffness in HC, in the rectus femoris, vastus lateralis, adductor magnus and
      gluteus maximus muscles. On muscle MRI T1-w images showed fatty replacement in
      3/5 patients at the level of the GM, while thigh and leg muscles were affected in
      2/5; hyperintensity on STIR images was identified in 4/5 patients. No significant
      correlation was observed between stiffness values and MRI scoring. Our study
      demonstrated that lower limb muscles of preschool DMD patients show fatty
      replacement and patchy edema on muscle MRI and increased stiffness on shear-wave
      elastography. In conclusion, although further studies in larger cohorts are
      needed, shear-wave elastography could be considered a useful non-invasive tool to
      easily monitor muscle changes in early stages of the disease.

PMID- 29661644
TI  - Structural brain alterations in autism and environmental exposure to nitrous
      oxide.

PMID- 29661645
TI  - Therapeutic management of people with epilepsy in low- and middle-income
      countries.

PMID- 29661646
TI  - Physical Activity to Improve Erectile Function: A Systematic Review of
      Intervention Studies.
AB  - INTRODUCTION: The leading cause of erectile dysfunction (ED) is arterial
      dysfunction, with cardiovascular disease as the most common comorbidity.
      Therefore, ED is typically linked to a web of closely interrelated cardiovascular
      risk factors such as physical inactivity, obesity, hypertension, and metabolic
      syndrome. Physical activity (PA) has proved to be a protective factor against
      erectile problems, and it has been shown to improve erectile function for men
      affected by vascular ED. This systematic review estimated the levels of PA needed
      to decrease ED for men with physical inactivity, obesity, hypertension, metabolic
      syndrome, and/or manifest cardiovascular diseases. AIM: To provide
      recommendations of levels of PA needed to decrease ED for men with physical
      inactivity, obesity, hypertension, metabolic syndrome, and/or cardiovascular
      diseases. METHODS: In accord with the Preferred Reporting Items for Systematic
      Reviews and Meta-Analyses (PRISMA) guidelines, a systematic review was performed
      of research articles specifically investigating PA as a possible treatment of ED.
      The review included research on ED from physical inactivity, obesity,
      hypertension, metabolic syndrome, and/or cardiovascular diseases. All available
      studies from 2006 through 2016 were checked for the predetermined inclusion and
      exclusion criteria to analyze the levels of PA needed to decrease ED. RESULTS: 10
      articles met the inclusion criteria, all suggesting various levels of PA needed
      to decrease ED for men with relevant risk factors for ED. The results of the
      review provided sufficient research evidence for conclusions regarding the levels
      of PA necessary to decrease ED. CONCLUSION: Recommendations of PA to decrease ED
      should include supervised training consisting of 40 minutes of aerobic exercise
      of moderate to vigorous intensity 4 times per week. Overall, weekly exercise of
      160 minutes for 6 months contributes to decreasing erectile problems in men with
      ED caused by physical inactivity, obesity, hypertension, metabolic syndrome,
      and/or cardiovascular diseases. Gerbild H, Larsen CM, Graugaard C, Areskoug
      Josefsson K. Physical Activity to Improve Erectile Function: A Systematic Review
      of Intervention Studies. Sex Med 2018;6:75-89.

PMID- 29661647
TI  - Which Ischemic Stroke Subtype Is Associated with Hyperhomocysteinemia?
AB  - BACKGROUND: Stroke is still a major global health problem in both developed and
      developing countries. Defining stroke subtype and underlying etiologies is a
      major step to choose the best method for prophylaxis. Homocysteine is an
      endothelial toxin and elevated levels have been associated with stroke risk. In
      this study, we hypothesized that serum total homocysteine level may be related
      with specific atherothrombotic ischemic stroke subtypes and aimed to find if high
      serum homocysteine levels are correlated with any specific ischemic stroke
      subtype. METHODS: Patients with ischemic stroke and aged between 18 and 65 are
      included. Ischemic stroke subtype is defined according to Causative
      Classification System. Hospital records are examined retrospectively to define
      patient demographics, ischemic stroke subtype, vascular risk factors, serum
      homocysteine, B12, and folic acid levels. RESULTS: A total of 262 patients were
      included. Serum homocysteine level was elevated (>=16 umol/L) in 99 patients
      (37.79%). The rate of patients with hyperhomocysteinemia was significantly more
      common in strokes due to intracranial stenosis (72.41%) (odds ratio 8.138; 95%
      confidence interval 2.366-27.989; P < .01) than extracranial large artery
      stenosis (52.00%), craniocervical arterial dissections (35.71%), cardioembolic
      strokes (27.87%), and lacunar infarctions (25.00%) after adjustment for other
      risk factors. High homocysteine levels were significantly more common in men and
      smokers (P < .05). CONCLUSIONS: Elevated levels of serum homocysteine are
      correlated with ischemic strokes due to intracranial large artery stenosis in
      young and middle-aged patients. This association may have an implication in
      stroke prophylaxis for intracranial atherosclerosis by using homocysteine
      lowering therapies.

PMID- 29661648
TI  - One year Rat Study of iBTA-induced "Microbiotube" Microvascular Grafts With an
      Ultra-Small Diameter of 0.6 mm.
AB  - OBJECTIVE: The world's smallest calibre "microbiotube" vascular graft was
      recently developed, with an inner diameter of 0.6 mm. It was formed using in-body
      tissue architecture (iBTA) and has a high degree of patency and capacity for
      regeneration in the acute phase, 1 month after implantation. This consecutive
      study investigated the compatibility and stability of microbiotubes in the
      chronic phase of implantation for 12 months for potential application in
      microsurgery. METHODS: This was an in vivo experimental study. The microbiotubes
      were prepared by embedding the mould subcutaneously in rats for 2 months.
      Allogenic microbiotubes (n = 16) were implanted into the bilateral femoral
      arteries (inner diameter 0.5 mm) of eight Wistar rats in an end to end
      anastomosis manner for 12 months. Follow up 7-Tesla magnetic resonance angiograms
      were performed every 3 months. Histological observation was performed 12 months
      after implantation. RESULTS: All patent grafts (n = 12, patency 75%) one month
      after implantation maintained their patency up to 12 months without any abnormal
      morphological changes or calcification. Histological observation at 12 months
      showed that layered alpha-smooth muscle actin positive cells with a monolayer
      luminal covering of endothelial cells had formed from the proximal to the distal
      anastomoses. A thin elastic fibre layer formed in the luminal area. After
      implantation, all components of the microbiotube were similar to those of a
      native artery. CONCLUSIONS: This study suggests that microbiotubes have high
      compatibility, stability, and durability as replacement grafts over the short to
      mid-term period.

PMID- 29661649
TI  - [Overal cognitive assessment in Basque-speaking people with advanced dementia.
      Validation to the Basque language of the Severe Mini-Mental State Examination
      SMMSE (SMMSE-eus)].
AB  - INTRODUCTION: Adaptation and validation to the Basque language of tests to assess
      advanced cognitive impairment is a not covered need for Basque-speaking people.
      The present work shows the validation of the Basque version of the Severe Mini
      Mental State Examination (SMMSE). MATERIAL AND METHODS: A total of 109 people
      with advanced dementia (MEC<15) took part in the validation study, and were
      classified as GDS 5-7 on the Geriatric Depression Scale (GDS). All participants
      were Spanish-Basque bilingual. RESULTS: It was shown that SMMSE-eus has a high
      internal consistency (alpha=0.92), a good test-retest reliability (r=0.88;
      P<.01), and a high inter-rater reliability (CCI=0.99; P<.00) for the overall
      score, as well as for each item. CONCLUSIONS: Both the high internal consistency
      and inter-rater reliability, and to a lesser extent, test-retest reliability,
      made the SMMSE-eus a valid test for the brief assessment of cognitive status in
      people with advanced dementia in Basque-speaking people. For this reason, the
      SMMSE-eus is a usable and reliable alternative for assessing Basque-speaking
      people in their mother-tongue, or preferred language.

PMID- 29661650
TI  - Community-acquired methicillin-resistant Staphylococcus aureus can persist in the
      throat.
AB  - Colonization by Staphylococcus aureus is an important factor in infections caused
      by this microorganism. Among the colonization niches of staphylococci are the
      nose, skin, intestinal tract, and, recently, the throat has been given relevance.
      Infections caused by community-acquired methicillin-resistant Staphylococcus
      aureus (CA-MRSA) can be fatal. Persistence of S. aureus is an important process
      in the pathogenesis of this microorganism and must be studied. The aim of this
      study was to determine the persistence of S. aureus in the throat, and
      characterized the strains. We studied the persistence of S. aureus for 6 years in
      the throat of apparently healthy people. The isolated strains from the persistent
      carriers were characterized through PFGE, spa-typing, SCCmec typing, resistance
      to methicillin, presence of virulence genes (adhesins and toxins), and the
      formation of biofilm. We found persistent and intermittent carriers of S. aureus
      in the throat, with methicillin-sensitive (MSSA), methicillin-resistant (MRSA)
      strains, and confirmed for the first time that CA-MRSA colonizes this niche.
      These strains can colonize persistently the throat for four years or more.
      Typification of strains through PFGE and spa-typing revealed that some carriers
      present the same strain, whereas others present different strains along the
      period of persistence. Almost all strains induced a strong biofilm formation. All
      strains presented adhesin and toxin genes, but no shared genotype was found. We
      conclude that S. aureus, including CA-MRSA strains, can remain persistently in
      the throat, finding a wide variability among the persistent strains.

PMID- 29661651
TI  - [Preferences of general practitioners in metropolitan France with regard to the
      delegation of medico-administrative tasks to secretaries assisting medico-social
      workers: Study in conjoint analysis].
AB  - BACKGROUND: A general practitioner's office is an economic unit where task
      delegation is an essential component in improving the quality and performance of
      work. AIM: To classify the preferences of general practitioners regarding the
      delegation of medical-administrative tasks to assistant medical-social
      secretaries. METHOD: Conjoint analysis was applied to a random sample of 175
      general practitioners working in metropolitan France. Ten scenarios were
      constructed based on seven attributes: training for medical secretaries,
      logistical support during the consultation, delegation of management planning,
      medical records, accounting, maintenance, and taking initiative on the telephone.
      A factorial design was used to reduce the number of scenarios. Physicians' socio
      demographic variables were collected. RESULTS: One hundred and three physicians
      responded and the analysis included 90 respondents respecting the transitivity of
      preferences hypothesis. Perceived difficulty was scored 2.8 out of 5. The high
      rates of respondents (59%; 95% CI [51.7-66.3]) and transitivity (87.5%; 95% CI
      [81.1-93.9]) showed physicians' interest in this topic. Delegation of tasks
      concerning management planning (OR=2.91; 95% CI [2.40-13.52]) and medical records
      (OR=1.88; 95% CI [1.56-2.27]) were the two most important attributes for
      physicians. The only variable for which the choice of a secretary was not taken
      into account was logistical support. CONCLUSION: This is a first study examining
      the choices of general practitioners concerning the delegation of tasks to
      assistants. These findings are helpful to better understand the determinants of
      practitioners' choices in delegating certain tasks or not. They reveal doctors'
      desire to limit their ancillary tasks in order to favor better use of time for
      "medical" tasks. They also expose interest for training medical secretaries and
      widening their field of competence, suggesting the emergence of a new
      professional occupation that could be called "medical assistant".

PMID- 29661652
TI  - Next generation sequencing reveals a high frequency of CXCR4 utilizing viruses in
      HIV-1 chronically infected drug experienced individuals in South Africa.
AB  - BACKGROUND: Entry inhibitors, such as Maraviroc, bind to CCR5 inhibiting entry of
      CCR5 utilizing viruses (R5 viruses). In the course of HIV infection, CXCR4
      utilizing viruses (X4 viruses) may emerge and outgrow R5 viruses, and potentially
      limit the effectiveness of Maraviroc. The use of Maraviroc is reserved for
      salvage therapy in South Africa. OBJECTIVE: In this study, we examined the
      frequency of R5 and X4 viruses, using next generation sequencing, in patients
      under treatment to draw inferences on the utility of Maraviroc in a South African
      population. STUDY DESIGN: Proviral DNA was isolated from peripheral blood
      mononuclear cells (PBMC) of 72 chronically HIV infected patients on
      antiretroviral treatment. HIV V3 loop gene was amplified and sequenced on an
      Illumina MiniSeq platform. Viral subtypes were determined by the jumping profile
      Hidden Markov Model (jpHMM) and REGA genotyping tools. De Novo consensus
      sequences were derived for the majority and minority populations for each patient
      using Geneious(r) software version 8.1.5. HIV-1 tropism was inferred using
      PSSMsinsi, Geno2pheno and Phenoseq-C web-based tools. RESULTS: Quality V3 loop
      sequences were obtained from 72 patients, with 5 years (range: 0-16) median
      duration on treatment. Subtypes A1, B and C viruses were identified at
      frequencies of 4% (3/72), 4% (3/72) and 92% (66/72) respectively. Fifty four
      percent (39/72) of patients exclusively harboured R5 viral quasispecies; and 21%
      (15/72) exclusively harbored X4 viral quasispecies. Twenty five percent of
      patients (18/72) harbored dual/mixture of R5X4 quasispecies. Of these 18
      patients, about 28% (5/18) harbored the R5+X4, a mixture with a majority R5 and
      minority X4 viruses, while about 72% (13/18) harbored the R5X4+ mixture with a
      majority X4 and minority R5 viruses. The proportion of all patients who harbored
      X4 viruses either exclusively or dual/mixture was 46% (33/72). Thirty-five
      percent (23/66) of the patients who were of HIV-1 subtype C harboured X4 viruses
      (chi2 = 3.58; p = .058), and 57% of these (13/23) harbored X4 viruses
      exclusively. CD4+ cell count less than 350 cell/MUl was associated with the
      presence of X4 viruses (chi2 = 4.99; p = .008). CONCLUSION: The effectiveness of
      Maraviroc as a component in salvage therapy may be compromised for a significant
      number of chronically infected patients harboring CXCR4 utilizing viruses.

PMID- 29661653
TI  - Radium-223 in the treatment of bone metastasis in patients with castration
      resistant prostate cancer. Review and procedure.
AB  - Bone metastatic disease is the main cause of morbidity / mortality in patients
      with prostate cancer, presenting frequently as bone pain, pathological fractures
      or spinal cord compression, which requires early and timely therapy. Although,
      for the moment, the therapeutic window for its use has not been definitively
      established, radium-223 (223Ra), an alpha particle emitter, has proved to be an
      effective therapeutic tool, pre or post-chemotherapy, in patients with castration
      resistant prostate cancer with symptomatic bone metastases and absence of
      visceral metastases, significantly modifying the prognosis of the disease. It is
      therefore imperative to define the ideal scenarios and the correct protocol for
      the use of this therapy and thus offer the greatest possible clinical benefit to
      the patient.

PMID- 29661654
TI  - The Tick Project: Testing Environmental Methods of Preventing Tick-borne
      Diseases: (Trends in Parasitology Vol 34, 447-450 2018).

PMID- 29661655
TI  - Reprint of Using ecological momentary assessments to predict relapse after adult
      substance use treatment.
AB  - BACKGROUND: A key component of relapse prevention is to self-monitor the internal
      (feelings or cravings) and external (people, places, activities) factors
      associated with relapse. Smartphones can deliver ecological momentary assessments
      (EMA) to help individuals self-monitor. The purpose of this exploratory study was
      to develop a model for predicting an individual's risk of future substance use
      after each EMA and validate it using a multi-level model controlling for repeated
      measures on persons. METHODS: Data are from 21,897 observations from 43 adults
      following their initial episode of substance use treatment in Chicago from 2015
      to 2016. Participants were provided smartphones for six months and asked to
      complete two to three minute EMAs at five random times per day (81% completion).
      In any given EMA, 2.7% reported substance use and 8% reported any use in the next
      five completed EMA. Chi-square Automatic Interaction Detector (CHAID) was used to
      classify EMAs into six levels of risk and then validated with a hierarchical
      linear model (HLM). RESULTS: The major predictors of substance use in the next
      five completed EMAs were substance use pattern over the current and prior five
      EMAs (no recent/current use, either recent or current use [but not both],
      continued use [both recent and current]), negative affect (feelings), and craving
      (rating). Negative affect was important for EMAs with no current or recent use
      reported; craving was important for EMAs with either recent or current use; and
      neither mattered for EMAs with continued use. The CHAID gradated EMA risk from
      0.7% to 36.6% of the next five completed EMAs with substance use reported. It
      also gradated risk of "any" use in the next five completed EMAs from 3% to 82%.
      CONCLUSIONS: This study demonstrated the potential of using smartphone-based EMAs
      to monitor and provide feedback for relapse prevention in future studies.

PMID- 29661656
TI  - Introduction to the special issue: Utilizing ambulatory assessment to better
      understand the etiology, maintenance, treatment, and remission of addictive
      disorders.

PMID- 29661657
TI  - Reprint of The effect of N-acetylcysteine and working memory training on cocaine
      use, craving and inhibition in regular cocaine users: correspondence of lab
      assessments and Ecological Momentary Assessment.
AB  - INTRODUCTION: Effective treatment for cocaine use disorder should dampen
      hypersensitive cue-induced motivational processes and/or strengthen executive
      control. Using a randomized, double-blind, placebo-controlled intervention, the
      primary aim of this study was to investigate the effect of N-Acetylcysteine (NAC)
      and working memory (WM)-training to reduce cocaine use and craving and to improve
      inhibition assessed in the laboratory and during Ecological Momentary Assessment
      (EMA). The second aim was to examine correspondence between laboratory and EMA
      data. METHODS: Twenty-four of 38 cocaine-using men completed a 25-day
      intervention with 2400mg/day NAC or placebo and WM-training as well as two lab
      visits assessing cocaine use, craving and inhibition (Stop Signal task).
      Additionally, cocaine use, craving and cognition (Stroop task) were assessed
      using EMA during treatment, with 26 participants completing 819 assessments.
      RESULTS: Cocaine problems according to the Drug Use Disorder Identification Test
      (DUDIT) decreased more after NAC than after placebo, and the proportion of
      cocaine-positive urines at lab-visit 2 was lower in the NAC group. No NAC effects
      were found on craving. For cocaine use and craving, results from the lab data
      were generally similar to EMA results. NAC also showed some effects on cognitive
      control: improved inhibition assessed with the Stop Signal task in the lab, and
      decreased classic Stroop performance during EMA. There were no significant
      effects of number of completed WM-training sessions. CONCLUSIONS: Overall this
      study revealed mixed findings regarding the treatment of cocaine use disorders
      with NAC and WM-training. The effect of NAC on inhibition should be further
      investigated.

PMID- 29661658
TI  - Is Transcellular Potassium Shifting With Insulin, Albuterol, or Sodium
      Bicarbonate in Emergency Department Patients With Hyperkalemia Associated With
      Recurrent Hyperkalemia After Dialysis?
AB  - BACKGROUND: Emergency department (ED) treatment of hyperkalemia often involves
      shifting potassium into the intracellular space. There is uncertainty whether
      transcellular shifting causes insufficient potassium removal during hemodialysis,
      resulting in a subsequent need for further medical therapy or multiple sessions
      of hemodialysis. OBJECTIVE: We sought to determine whether transcellular
      potassium shifting in ED patients with hyperkalemia who undergo hemodialysis is
      associated with recurrent hyperkalemia with or without repeat hemodialysis within
      24 h. METHODS: This was a retrospective observational study of ED patients with a
      potassium value > 5.3 mmol/L and >=1 hemodialysis run. Transcellular shifting
      medications were defined as albuterol, insulin, and sodium bicarbonate. Primary
      outcomes were recurrent hyperkalemia with and without repeat hemodialysis within
      24 h of the initial dialysis run. Generalized estimating equation models were
      created for the outcomes using administration of a shifting medication as the
      primary predictor. RESULTS: Four hundred seventy-nine encounters were identified.
      In 238 (50%) encounters, a shifting medication was administered. There were 85
      outcomes of recurrent hyperkalemia and 36 outcomes of recurrent hyperkalemia with
      repeat hemodialysis. After adjustment, administration of shifting medications was
      not associated with recurrent hyperkalemia (adjusted odds ratio 1.26, 95%
      confidence interval 0.71-2.23) or recurrent hyperkalemia with repeat dialysis
      (adjusted odds ratio 1.90, 95% confidence interval 0.80-4.48). CONCLUSIONS:
      Administration of transcellular shifting medications for hyperkalemia in the ED
      was not associated with either recurrent hyperkalemia after hemodialysis or the
      need for a second dialysis session within 24 h. Our findings address the
      uncertainty regarding transcellular potassium shifting before emergent dialysis
      and support safe ED administration of medications that shift potassium to the
      intracellular space.

PMID- 29661659
TI  - The Association Between Heat Waves and Other Meteorological Parameters and
      Snakebites: Israel National Study.
AB  - BACKGROUND: Published annual estimates report a global burden of 2.5 million
      snakebite cases and >100,000 deaths. In Israel, envenomations are the third most
      frequent cause of poisonings that are of moderate to major clinical severity.
      Most studies focus on the clinical descriptions of snakebites in tropical
      climates, and we sought to investigate the association between snakebite
      frequency and meteorological parameters. OBJECTIVE: We sought to investigate the
      seasonality of snakebites and evaluate the association between increasingly
      common heat waves and other meteorological parameters and snakebite frequency in
      a semiarid nontropical climate. METHODS: We obtained data for all medical
      evacuations (2008-2015) because of snakebites in Israel. Climate data included
      daily 24-hour average temperature ( degrees C) and relative humidity (%). We used
      a time-stratified case crossover method, in which a conditional logistic
      regression was applied to estimate the association, and we also stratified our
      analysis by season and by region. RESULTS: We identified 1234 snakebite cases
      over 8 years, of which most (74.2%) occurred in hot seasons and between 6 pm and
      9 pm. The risk of snakebite was positively associated with temperature >23
      degrees C (odds ratio [OR] 1.24, 95% confidence interval [CI] 1.01-1.53) and
      inversely with humidity >40% (OR 0.74, 95% CI 0.57-0.97). We also found an
      association with heat waves both in cold (OR 1.62, 95% CI 1.01-2.60) and hot
      seasons (OR 1.50, 95% CI 1.18-1.92). CONCLUSIONS: In a semiarid nontropical
      climate, we observed an association between an increase in the number of
      snakebite cases and higher temperatures and lower humidity. Moreover, heat waves
      increased the frequency of snakebites in both cold and hot seasons.

PMID- 29661660
TI  - Epipremnum aureum and Dracaena braunii as indoor plants for enhanced bio
      electricity generation in a plant microbial fuel cell with electrochemically
      modified carbon fiber brush anode.
AB  - In this study, two different unexploited indoor plants, Epipremnum aureum and
      Dracaena braunii were used to produce clean and sustainable bio-electricity in a
      plant microbial fuel cell (PMFC). Acid modified carbon fiber brush electrodes as
      well as bare electrodes were used in both the PMFCs. A bentonite based clay
      membrane was successfully integrated in the PMFCs. Maximum performance of E.
      aureum was 620 mV which was 188 mV higher potential than D. braunii. The bio
      electricity generation using modified electrode was 154 mV higher than the bare
      carbon fiber, probably due to the effective bacterial attachment to the carbon
      fiber owing to hydrogen bonding. Maximum power output of 15.38 mW/m2 was obtained
      by E. aureum with an internal resistance of 200 Omega. Higher biomass yield was
      also obtained in case of E. aureum during 60 days of experiment, which may
      correlate with the higher bio-electricity generation than D. braunii.

PMID- 29661661
TI  - Three-dimensional study of 31 cases of synostotic anterior plagiocephaly before
      and after surgical management the Lille protocol.
AB  - Synostotic anterior plagiocephaly is a rare pathological cranial malformation.
      Therapeutic options are rarely studied due to the rarity of the malformation and
      difficulties in diagnosis and care management. The objective of this study was to
      analyze the results obtained with the Lille protocol based on 62 CT-scans done
      before and after surgery in 31 patients. A specific analysis was designed for
      this work. Nine cephalometric measures enabled to evidence on each CT-Scan the
      corrections made on the fronto-orbital bandeau and the potential impact of
      surgery on the craniofacial structures. Results show that surgical symmetry of
      the fronto-orbital bandeau in the transversal plane, according to the symmetrical
      axis of the semicircular canals, allows a normalization of the skull's growth and
      morphogenesis for the surgically affected structures but also adjacent ones.

PMID- 29661662
TI  - Multimodal analysis using flowmeter analysis, laser-Doppler spectrophotometry,
      and indocyanine green videoangiography for the detection of venous compromise in
      flaps in rats.
AB  - Venous congestion results in tissue damage and remains the most common failure of
      free microvascular transfer if it is not recognized early. The purpose of this
      experimental study was to evaluate venous congestion and describe the findings
      with two different monitoring tools. A standardized epigastric flap was raised,
      and total occlusion of the draining vein was temporarily applied for 4, 5, 6, or
      7 h. Blood flow measurements, including laser-Doppler flowmetry, and tissue
      spectrophotometry (O2C) and indocyanine green (ICG) videoangiography using the
      FLOW(r) 800 tool, were performed systematically after each surgical step, an
      interval of venous occlusion, and 1 week of clinical observation. Both monitoring
      tools were capable of detecting acute venous occlusion. ICG videoangiography data
      showed a significant decrease in the first and second maximum, and the area under
      the curve, during venous occlusion, whereas hemoglobin levels in the O2C analysis
      remained stable. Changes in fluorescence values in border areas of the flap
      correlated significantly with the incidence of necrosis. O2C data later showed
      significant correlation with the area of necrosis, and more individual changes
      during flap monitoring. ICG videoangiography might therefore be useful in the
      prediction of flap necrosis in critical areas of perfusion.

PMID- 29661663
TI  - Right on target?
AB  - Targets have become an integral part of health care, whether we agree with them
      or not. Many accept the progress made with the use of targets, but our duty as
      health professionals is to ensure that their use and interpretation is undertaken
      with the same care and understanding of their limitations that we apply to our
      clinical practice, and that they are not mis-interpreted or used to justify the
      latest political idioms. Currently the healthcare profession is failing to
      understand the consequences of setting targets, or the wider implications of
      hitting them. This article aims to summarise how we can learn from past
      experiences to become more aware of the benefits and draw-backs of targets in
      healthcare, and how we can utilise them more efficiently in health care.

PMID- 29661664
TI  - Temporal variations in dispatcher-assisted and bystander-initiated resuscitation
      efforts.
AB  - PURPOSE: To investigate temporal variations in dispatcher-assisted and bystander
      initiated resuscitation efforts and their association with survival after
      bystander-witnessed out-of-hospital cardiac arrests (OHCAs). METHODS: We
      retrospectively analyzed the neurologically favorable 1-month survival and the
      parameters related to dispatcher assisted cardiopulmonary resuscitation (DA-CPR)
      and bystander CPR (BCPR) for 227,524 OHCA patients between 2007 and 2013 in
      Japan. DA-CPR sensitivity for OHCAs, bystander's compliance to DA-CPR assessed by
      the proportion of bystanders who follow DA-CPR, and performance of BCPR measured
      by the rate of bystander-initiated CPR in patients without DA-CPR were calculated
      as indices of resuscitation efforts. RESULTS: Performance of BCPR was only
      similar to temporal variations in the survival (correlation between hourly paired
      values, R2=0.263, P=0.01): a lower survival rate (3.4% vs 4.2%) and performance
      of BCPR (23.1% vs 30.8%) during night-time (22:00-5:59) than during non-night
      time. In subgroup analyses based on interaction tests, all three indices
      deteriorated during night-time when OHCAs were witnessed by non-family (adjusted
      odds ratio, 0.73-0.82), particularly in non-elderly patients. The rate of public
      access defibrillation for these OHCAs markedly decreased during night-time
      (adjusted odds ratio, 0.49) with delayed emergency calls and BCPR initiation.
      Multivariable logistic regression analyses revealed that the survival rate of non
      family-witnessed OHCAs was 1.83-fold lower during night-time than during non
      night-time. CONCLUSIONS: Dispatcher-assisted and bystander-initiated
      resuscitation efforts are low during night-time in OHCAs witnessed by non-family.
      A divisional alert system to recruit well-trained individuals is needed in order
      to improve the outcomes of night-time OHCAs witnessed by non-family bystanders.

PMID- 29661665
TI  - Combining early post-resuscitation EEG and HRV features improves the prognostic
      performance in cardiac arrest model of rats.
AB  - OBJECTIVE: Early and reliable prediction of neurological outcome remains a
      challenge for comatose survivors of cardiac arrest (CA). The purpose of this
      study was to evaluate the predictive ability of EEG, heart rate variability (HRV)
      features and the combination of them for outcome prognostication in CA model of
      rats. METHODS: Forty-eight male Sprague-Dawley rats were randomized into 6 groups
      (n=8 each) with different cause and duration of untreated arrest. Cardiopulmonary
      resuscitation was initiated after 5, 6 and 7min of ventricular fibrillation or 4,
      6 and 8min of asphyxia. EEG and ECG were continuously recorded for 4h under
      normothermia after resuscitation. The relationships between features of early
      post-resuscitation EEG, HRV and 96-hour outcome were investigated. Prognostic
      performances were evaluated using the area under receiver operating
      characteristic curve (AUC). RESULTS: All of the animals were successfully
      resuscitated and 27 of them survived to 96h. Weighted-permutation entropy (WPE)
      and normalized high frequency (nHF) outperformed other EEG and HRV features for
      the prediction of survival. The AUC of WPE was markedly higher than that of nHF
      (0.892 vs. 0.759, p<0.001). The AUC was 0.954 when WPE and nHF were combined
      using a logistic regression model, which was significantly higher than the
      individual EEG (p=0.018) and HRV (p<0.001) features. CONCLUSIONS: Earlier post
      resuscitation HRV provided prognostic information complementary to quantitative
      EEG in the CA model of rats. The combination of EEG and HRV features leads to
      improving performance of outcome prognostication compared to either EEG or HRV
      based features alone.

PMID- 29661666
TI  - Pseudo-Wellens' syndrome and intermittent left bundle branch block in acute
      cholecystitis.
AB  - We present a case of a 54-year-old male patient who was admitted to our Emergency
      Department (ED) with localized epigastric pain. Inflammation markers, ultrasound,
      and CT scan were inconsistent with an initial diagnosis of cholecystitis.
      However, there was additional evidence of cholecystolithiasis. The ECG showed new
      anterior biphasic T waves typical for a Wellens' type A ECG. Additionally, the
      patient had an intermittent left bundle branch block (LBBB). The diagnostic
      challenges in differentiating possible diagnoses will be described, to which in
      this case, were either acute cholecystitis or acute coronary syndrome (ACS). A
      laparoscopic study confirmed acute cholecystitis. Coronary angiography showed no
      pathological processes associated with ACS. ECG abnormalities were initially
      ongoing, but were no longer detectable during an 8month follow up assessment.

PMID- 29661667
TI  - Quantifying the operational impact of boarding inpatients on emergency department
      radiology services.

PMID- 29661668
TI  - No association between metoclopramide treatment in ED and reduced risk of post
      concussion headache.
AB  - OBJECTIVE: There is a lack of definitive pediatric literature on effective
      pharmacotherapy for persistent post-concussion headache symptoms. This study
      assessed whether acute metoclopramide treatment in the Emergency Department (ED)
      was associated with a reduction in persistent headache in children at 1- and 4
      weeks post-concussion. METHODS: Children aged 8-17years with acute concussion
      presenting to 9-Canadian Pediatric EDs were enrolled in a prospective cohort
      study, from August 2013-June 2015. Primary and secondary outcomes were persistent
      headache at 1- and 4-week post-injury respectively. Headache persistence was
      based on the one and four-week headache scores minus recalled pre-injury score
      using the Post-Concussion Symptom Inventory. The association between
      metoclopramide and headache persistence at 1- and 4-weeks were examined using
      unadjusted and adjusted regression and 1:4 propensity score matching model.
      RESULTS: Baseline assessments were completed in 2095 participants; 65 (3.1%)
      received metoclopramide within 48-hours of injury. At 1- and 4-weeks, 54%
      (963/1808) and 26% (456/1780) of participants had persistent headache relative to
      baseline respectively. In unadjusted analysis, no association between
      metoclopramide and headache persistence at 1-week was found [treated vs.
      untreated: 1-week (53% vs. 53%; relative risk (RR)=1.0 (95%CI: 0.8, 1.3); 4-weeks
      (27.3% vs. 25.6%; RR=1.0 (95% CI: 0.9, 1.2)]. Metoclopramide was not associated
      with lower headache risk on propensity score matching [treated vs. untreated: 1
      week, n=220 (52% vs. 59.4%; RR=0.8 (95%CI: 0.6, 1.2) and 4-weeks, n=225 (27.1%
      vs. 32.8%; RR=0.9 (95%CI: 0.8, 1.1)]. CONCLUSION: Metoclopramide administration
      was not associated with a reduction in headache persistence in children seeking
      ED care due to a concussion. Further research is necessary to determine which
      pharmacotherapies may be effective for acute and persistent post-concussive
      headache.

PMID- 29661669
TI  - Interventional catheterization and echocardiography: An indefectible link
      illustrated by atrial septal defect closure.

PMID- 29661670
TI  - [Community-acquired pneumonia in patients with chronic obstructive pulmonary
      disease treated with inhaled corticosteroids or other bronchodilators. Study
      PNEUMOCORT].
AB  - OBJECTIVES: To analyse the risk of pneumonia and/or exacerbations in patients
      with chronic obstructive pulmonary disease (COPD) who receive treatment with
      inhaled corticosteroids (CI), in comparison with those who are not treated with
      inhaled corticosteroids (NCI). To estimate the risk of pneumonia according to CI
      dose. DESIGN: Population-based cohort study. SETTING: Primary Healthcare.
      Institut Catala de la Salut. PARTICIPANTS: Patients >=45 years-old diagnosed with
      COPD between 2007 and 2009 in the Information System for Research in Primary Care
      (SIDIAP). INTERVENTION: Two cohorts; patients initiating CI and patients
      initiating bronchodilators after COPD diagnosis. MAIN MEASUREMENTS: Demographics,
      smoking, medical history, pneumonias, exacerbations, vaccinations, and drug
      therapy. RESULTS: A total of 3,837 patients were included, 58% in the CI and 42%
      in the NCI group. Higher incidence rates of pneumonia and exacerbations were
      detected in the CI group compared with the NCI (2.18 vs. 1.37). The risk of
      pneumonia and severe exacerbations was not significantly different between
      groups, HR; 1.17 (95% CI; 0.87-1.56) and 1.06 (95% CI; 0.87-1.31), respectively.
      Patients in the CI group had a higher risk of mild exacerbations, HR; 1.28 (95%
      CI; 1.10-1.50). Variables associated with a higher risk of pneumonia were age,
      diabetes, previous pneumonias and bronchitis, very severe COPD, treatment with
      low doses of beta2-adrenergic or anticholinergic agents, and previous treatment
      with oral corticosteroids. CONCLUSIONS: There were no differences between cohorts
      in the risk of pneumonia and severe exacerbations. The risk of mild exacerbations
      was higher in the CI group. Pneumonias and severe exacerbations were more
      frequent in patients with severe COPD and in patients receiving high doses of CI.

PMID- 29661671
TI  - [Behaviour and attitudes towards the sexuality of the pregnant woman during the
      last trimester. Phenomenological study].
AB  - OBJECTIVE: To explore the life experiences on sexual relationships in the third
      trimester of pregnancy in primiparous women. DESIGN: Phenomenological qualitative
      study, SITE: Caceres (Extremadura). PARTICIPANTS: Primiparous women in the third
      trimester of their pregnancy. METHODS: We use theoretical sampling, was conducted
      on pregnant primiparous. The study included 15 participants. The data was
      collected using in-depth interviews, that were voiced recorded and later
      transcribed. The analysis was made using Giorgi's proposal. RESULTS: The results
      show three main points. Fear of doing damage, mediated by the obstetric history
      and the desire to have the long-awaited child. Exploring new routes: forms of
      sexual expression are modified by the physical changes, the fears, and the
      mobility. Highlighting the importance of other displays of affection and love
      (kisses and caresses). The Sex Taboo: lack of information against sexuality
      during pregnancy is still common. CONCLUSIONS: Women in the third trimester of
      their pregnancy put aside their sexual appetite and that of their partners, and
      concentrate in the wellbeing of their new born baby. It highlights the role of
      the mother before the couple. The more desired and difficult the pregnancy has
      been, the more the sexual life is reduced. The Health Professionals must advise
      and inform the couples with an open-minded attitude.

PMID- 29661672
TI  - Development and Validation of the Foot Union Scoring Evaluation Tool for
      Arthrodesis of Foot Structures.
AB  - Reliable evaluation of osseous consolidation after pedal arthrodesis can be
      difficult, and the presence or absence of radiographic healing often dictates
      care. Plain radiographs remain the mainstay imaging tool owing to their cost,
      efficiency, and low radiation exposure. Applying radiographic parameters that can
      reliably determine osseous healing is essential. However, currently, no reliable
      or validated measures are available to determine osseous union of any joint in
      the foot or ankle. The purpose of the present study was to develop a radiographic
      healing scoring system that would enhance the diagnostic healing assessment after
      joint arthrodesis of the foot or ankle. We adapted several existing scales
      previously validated for fracture healing in the leg, because no study has
      attempted to apply this to a joint fusion model. A total of 150 cases were
      evaluated by 6 blinded assessors to test the interrater reliability of the
      subjective healing assessment compared with the proposed scoring system. The
      radiographs were classified by the postoperative period: <=4 weeks, 5 to 12
      weeks, and >12 weeks. The initial proposed scale was found to have high
      interrater reliability but was burdensome. Using a priori item reduction
      protocols, a limited 5-item scale further improved the internal consistency and
      reduced the burden. The result was excellent interrater reliability (alpha =
      0.978, standard deviation 0.02, 95% confidence interval 0.96 to 0.99) among all
      assessors compared with the reduced reliability (alpha = 0.752) for subjective
      arthrodesis healing. Intrarater reliability was also found to be superior using a
      test-retest method. The reliability of this system appeared superior to the
      subjective assessment of arthrodesis healing, even in the absence of clinical
      correlates, after foot arthrodesis.

PMID- 29661673
TI  - The Use of Pediatric Flexible Intramedullary Nails for Minimally Invasive Fibular
      Fracture Fixation.
AB  - Fibular fractures in the setting of an unstable ankle joint require surgical
      fixation; however, several factors contradict open surgical correction. Severe
      soft tissue compromise can delay adequate fracture reduction and preclude the
      standard incisional approach. The soft tissue envelope in the setting of obesity,
      diabetes, and/or peripheral vascular disease further complicates definitive
      treatment. Poorly timed open fixation can lead to delayed healing of the incision
      site, with wound breakdown and the potential for hardware failure. Proximal
      fibular fractures are also at unique risk of neurovascular compromise with open
      reduction and internal fixation. Surgical fixation has now focused on minimizing
      the soft tissue insult using percutaneous techniques in the comorbid patient. We
      present a case that highlights a minimally invasive technique that provides
      dynamic stable internal fixation of fibular fractures with the use of flexible
      pediatric intramedullary nails, typically used in long bone fractures of
      children.

PMID- 29661674
TI  - Evaluation of Transsyndesmotic Fixation and Primary Deltoid Ligament Repair in
      Ankle Fractures With Suspected Combined Deltoid Ligament Injury.
AB  - The present prospective study examined the utility of the intraoperative tap
      test/technique for distal tibiofibular syndesmosis in the diagnosis of deltoid
      ligament rupture and compared the outcomes of transsyndesmotic fixation to
      deltoid ligament repair with suture anchor. This diagnostic technique was
      performed in 59 ankle fractures with suspected deltoid ligament injury. The width
      of the medial clear space of 59 cases was evaluated to assess the sensitivity and
      specificity. Those with deltoid ligament rupture were randomly assigned to 2
      groups and treated with deltoid ligament repair with a suture anchor or with
      syndesmosis screw fixation. All the patients were assessed with the American
      Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scale, short-form 36
      item questionnaire (SF-36), and visual analog scale (VAS). The tap test was
      positive in 53 cases. However, surgical exploration demonstrated that 51 cases
      (86.4%) had a combined deltoid ligament injury and fracture. The sensitivity and
      specificity of the tap test was 100.0% and 75.0%, respectively. Finally, 26 cases
      (96.3%) in the syndesmosis screw group and 22 (91.7%) in the deltoid repair group
      were followed up. No statistically significant differences were found in the
      AOFAS ankle-hindfoot scale score, SF-36 score, or VAS score between the 2 groups.
      The malreduction rate in the syndesmosis screw group was 34.6% and that in the
      deltoid repair group was 9.09%. The tap test is an intraoperative diagnostic
      method to use to evaluate for deltoid ligament injury. Deltoid ligament repair
      with a suture anchor had good functional and radiologic outcomes comparable to
      those with syndesmotic screw fixation but has a lower malreduction rate. We did
      not encounter the issue of internal fixation failure or implant removal.

PMID- 29661675
TI  - Burnt sugarcane harvesting is associated with rhinitis symptoms and inflammatory
      markers.
AB  - INTRODUCTION: Burnt sugarcane harvesting requires intense physical exertion in an
      environment with high temperatures and exposure to particulate matter. OBJECTIVE:
      To evaluate the effects of burnt sugarcane harvesting on rhinitis symptoms and
      inflammatory markers in sugarcane workers. METHODS: 32 male sugarcane workers
      were evaluated with questionnaire for rhinitis symptoms, and for inflammatory
      markers on peripheral blood and nasal lavage, in the non-harvesting, and 3 and 6
      months into the sugarcane harvesting period. Weather data and particulate matter
      fine concentrations were measured in the same day. RESULTS: The particulate
      matter concentrations in sugarcane harvesting were 27 (23-33MUg/m3), 112 (96
      122MUg/m3), and 63 (17-263MUg/m3); 24h temperatures were 32.6 (25.4-37.4 degrees
      C), 32.3 (26.7-36.7 degrees C) and 29.7 (24.1-34.0 degrees C) and relative
      humidities were 45.4 (35.0-59.7%), 47.9 (39.1-63.0%), and 59.9 (34.7-63.2%) in
      the non-harvesting period, three and 6 months of the harvesting period. The age
      was 37.4+/-10.9 years. The prevalence of rhinitis symptoms was significantly
      higher at 3 months of the harvesting period (53.4%), compared to non-harvesting
      period (26.7%; p=0.039) and at 6 months into the harvesting period (20%;
      p=0.006). Concentrations of interleukin 6 (IL-6) in nasal lavage increased after
      3 months of the harvesting period compared to the non-harvesting period
      (p=0.012). The presence of rhinitis symptoms, after 3 months of the harvesting
      period, was directly associated with blood eosinophils and inversely associated
      with neutrophils. CONCLUSIONS: After 3 months of work in burnt sugarcane
      harvesting the prevalence of rhinitis symptoms and IL-6 in nasal lavage
      increased. Furthermore, eosinophil counts were directly associated with the
      rhinitis symptoms in the period of higher concentration of particulate matter.

PMID- 29661676
TI  - ?

PMID- 29661677
TI  - Orthodontic-periodontal interactions: Orthodontic extrusion in interdisciplinary
      regenerative treatments.
AB  - Orthodontics is a periodontal treatment. "Guided orthodontic regeneration" (GOR)
      procedures use orthodontic movements in perio-restorative patients. The GOR
      technique includes a guided orthodontic "soft tissue" regeneration (GOTR) and a
      guided orthodontic "bone" regeneration (GOBR) with a plastic soft tissue approach
      and a regenerating reality. The increased amount of soft tissue gained with
      orthodontic movement can be used for subsequent periodontal regenerative
      techniques. The increased amount of bone can as well improve primary implant
      stability and, eventually, simplify a GTR technique to regenerate soft tissues,
      to restore tooth with external resorption in aesthetic zone or to extract a tooth
      to create new hard-soft tissue for adjacent teeth.

PMID- 29661678
TI  - Effect of predosing versus slow administration of propofol on the dose required
      for anaesthetic induction and on physiologic variables in healthy dogs.
AB  - OBJECTIVE: To investigate the effects of the timing of propofol administration on
      the dose required for induction of anaesthesia and commonly measured
      physiological effects. STUDY DESIGN: Randomized, investigator-blinded clinical
      study. ANIMALS: A group of 32 healthy dogs aged 6-144 months and weighing 3.5
      47.2 kg. METHODS: Premedication was intramuscular acepromazine (0.025 mg kg-1)
      and methadone (0.25 mg kg-1). After 30 minutes, one of three treatments was
      administered to the dogs: propofol (0.5 mg kg-1; group PP), an equivalent volume
      of saline (group CP) or a propofol infusion (1.3 mg kg-1 minute-1; group SI). Two
      minutes later, a propofol infusion (4 mg kg-1 minute-1) was started in PP and CP,
      whereas the propofol infusion was continued in SI. At this stage an investigator,
      blinded to the group assignments, entered the room and decided when each animal
      was ready for intubation and stopped the propofol infusion. After intubation,
      management of anaesthesia was standardized. Pulse rate (PR), respiratory rate
      (fR) and mean arterial pressure (MAP) were recorded before induction, 2 minutes
      later and 0, 2 and 5 minutes after intubation. Apnoea >30 seconds was recorded
      and managed. Sedation, quality of induction and endotracheal intubation were
      scored using simple descriptive scales. Data are presented as mean+/-standard
      deviation. RESULTS: Propofol dose requirement was lower in SI (3.5+/-1.2 mg kg-1)
      compared with PP and CP (5.0+/-0.9 and 4.8+/-0.6 mg kg-1; p=0.002 and 0.012),
      respectively. No statistically significant differences were found among groups
      for PR, fR, MAP or incidence of apnoea. Sedation score and quality of induction
      were similar among groups. CONCLUSIONS: Slow administration of propofol reduced
      the anaesthetic induction dose required compared with predosing and control
      groups. Effects on PR, fR, MAP and apnoea were similar among groups. CLINICAL
      RELEVANCE: Slower injection of propofol reduces the dose required for induction
      of anaesthesia.

PMID- 29661679
TI  - Methodological challenges in using point-prevalence versus cohort data in risk
      factor analyses of nosocomial infections.
AB  - PURPOSE: To explore the impact of length-biased sampling on the evaluation of
      risk factors of nosocomial infections (NIs) in point-prevalence studies. METHODS:
      We used cohort data with full information including the exact date of the NI and
      mimicked an artificial 1-day prevalence study by picking a sample from this
      cohort study. Based on the cohort data, we studied the underlying multistate
      model which accounts for NI as an intermediate and discharge/death as competing
      events. Simple formulas are derived to display relationships between risk,
      hazard, and prevalence odds ratios. RESULTS: Due to length-biased sampling, long
      stay and thus sicker patients are more likely to be sampled. In addition,
      patients with NIs usually stay longer in hospital. We explored mechanisms that
      are-due to the design-hidden in prevalence data. In our example, we showed that
      prevalence odds ratios were usually less pronounced than risk odds ratios but
      more pronounced than hazard ratios. CONCLUSIONS: Thus, to avoid
      misinterpretation, knowledge of the mechanisms from the underlying multistate
      model is essential for the interpretation of risk factors derived from point
      prevalence data.

PMID- 29661680
TI  - Individual-level key associations and modes of exposure for hepatitis C virus
      infection in the Middle East and North Africa: a systematic synthesis.
AB  - PURPOSE: To identify, map, and synthesize the individual-level key associations
      and modes of exposure for hepatitis C virus (HCV) infection in the Middle East
      and North Africa (MENA), the most affected region by HCV. METHODS: Source of data
      was the MENA HCV Epidemiology Synthesis Project database, populated through
      systematic literature searches. Risk factors determined to be statistically
      significant after adjustment for confounders were extracted and categorized into
      key associations or modes of exposure. RESULTS: In total, 329 risk factors were
      identified from 109 articles in 14 of 24 MENA countries. Among key associations,
      age was most frequently reported (n = 39; 34.2%), followed by other
      infections/diseases (n = 20; 17.5%), and incarceration (n = 17; 14.9%). Among
      modes of exposure, health care-related exposures were most frequently reported (n
      = 127; 59.5%), followed by injecting drug use exposures (n = 45; 20.9%),
      community-related exposures (n = 34; 15.8%), and sexual-related exposures (n = 8;
      3.7%). Blood transfusion, hemodialysis, surgical and other medical procedures,
      dental work, and medical injections were identified as key health care-related
      exposures. CONCLUSIONS: Health care appears to be the primary driver of prevalent
      (and possibly incident) infections in MENA, followed by injecting drug use. HCV
      screening should target the identified modes of exposure. Commitment to
      prevention should be an integral component of HCV response to achieve HCV
      elimination by 2030, with focus on strengthening infection control in health care
      facilities, improving injection safety and blood screening, and expanding harm
      reduction services for people who inject drugs.

PMID- 29661681
TI  - A Rapamycin-Activated Caspase 9-Based Suicide Gene.
AB  - Engineered T cell therapies show considerable promise in the treatment of
      refractory malignancies. Given the ability of engineered T cells to engraft and
      persist for prolonged periods along with unpredicted toxicities, incorporation of
      a suicide gene to allow selective depletion after administration is desirable.
      Rapamycin is a safe and widely available immunosuppressive pharmaceutical that
      acts by heterodimerization of FKBP12 with the FRB fragment of mTOR. The apical
      caspase caspase 9 is activated by homodimerization through its CARD domain. We
      developed a rapamycin-induced caspase 9 suicide gene. First, we showed that
      caspase 9 could be activated by a two-protein format with replacement of the CARD
      domain with both FRB and FKBP12. We next identified an optimal compact single
      protein rapamycin caspase 9 (rapaCasp9) by fusing both FRB and FKBP12 with the
      catalytic domain of caspase 9. Functionality of rapaCasp9 when co-expressed with
      a CD19 CAR was demonstrated in vitro and in vivo.

PMID- 29661682
TI  - Absolute immature platelet counts in the setting of suspected heparin-induced
      thrombocytopenia may predict anti-PF4-heparin immunoassay testing results.
AB  - BACKGROUND: Heparin-induced-thrombocytopenia (HIT) is a disease mediated by
      antibodies to platelet factor 4 (PF4)-heparin complexes. Immature platelet
      fraction (%-IPF) and absolute immature platelet count (A-IPC) measure newly
      released platelets into circulation and can prove useful in differentiating
      patients with thrombocytopenic presentations due to consumptive or hypoproduction
      processes. Therefore, we evaluated utility of A-IPC in a cohort of
      thrombocytopenic patients suspected of HIT. PATIENTS AND METHODS: Twenty-six
      thrombocytopenic patients (<150 * 109/L) tested for anti-PF4-heparin and 36 non
      thrombocytopenic controls were included. Platelet count, %-IPF, and A-IPC were
      determined at time of anti-PF4-heparin testing. RESULTS: Sixteen patients tested
      anti-PF4-heparin negative and 10 tested positive. Patients with positive anti-PF4
      heparin did not differ in A-IPC from normal range (7.2 +/- 2.9 * 109/L vs. 7.1 +/
      3.2 * 109/L respectively; p = 0.97). However, there was a significant A-IPC
      decrease in patients negative for anti-PF4-heparin compared to normal range and
      those testing anti-PF4-heparin positive (4.2 +/- 3.1 * 109/L vs. 7.1 +/- 3.2 *
      109/L vs. 7.2 +/- 2.9 * 109/L respectively, p < 0.01). An A-IPC of greater than 5
      * 109/L characterized 80% of anti-PF4-heparin positive cases. CONCLUSION: A-IPC
      measurements can complement anti-PF4-heparin testing of patients suspected of HIT
      while potentially predicting anti-PF4-heparin immunoassay results.

PMID- 29661683
TI  - Healthy living: A health promotion program for adults with intellectual
      disability.
AB  - BACKGROUND: Adults with intellectual disability are more likely to experience a
      range of physical and mental health problems in comparison to the general
      population. However with access to appropriate health care and promotion, many of
      these health problems can be prevented. OBJECTIVE: To explore the perspectives of
      stakeholders of a health promotion program established for adults with
      intellectual disability. METHODS: Semi-structured interviews were conducted with
      12 stakeholders of a health promotion program. Stakeholders included adults with
      intellectual disability (n = 6), their support persons (n = 4) and program
      presenters (n = 2). Adults with intellectual disability included three males and
      three females with a mean age of 45.5 years (range 37-51 years). Interviews were
      digitally recorded and transcribed verbatim. Transcripts were analysed using
      thematic analysis. RESULTS: Four main themes emerged from the data. The first
      theme highlights the positive feedback all stakeholders, especially adults with
      intellectual disability, had for the program and the second focuses on
      suggestions for changes to improve it. The third and final themes explore how
      having input from adults with intellectual disability and their support persons,
      who have a unique understanding of their needs, could be better incorporated into
      the development of the program. CONCLUSIONS: This health promotion program has
      been well received by people with intellectual disability when incorporated into
      their weekly social club meetings With encouragement and training, people with
      intellectual disability and their support workers could be more involved in the
      development of the program to ensure it is relevant to their needs.

PMID- 29661684
TI  - Trabecular Bone Score and Hip Structural Analysis in Patients With Atypical Femur
      Fractures.
AB  - Bisphosphonate use has declined dramatically in recent years, partly because of
      fear of rare side effects like atypical femur fractures (AFFs). It is therefore
      desirable to have a diagnostic method to identify those at risk of AFF to prevent
      this serious complication. We compared trabecular microarchitecture and hip
      geometry between 30 patients with AFF and 141 controls of similar age and sex,
      using bisphosphonates. Trabecular bone score (TBS) and hip structural analysis
      (HSA) were used to assess trabecular microarchitecture and macroscopic hip
      geometry from dual-energy X-ray absorptiometry images of the lumbar spine and
      hip, respectively. General characteristics, TBS, and HSA were compared between
      patients with AFF and controls using Student's t tests and chi-square statistics.
      Associations between AFF and TBS and femur geometric characteristics by HSA were
      adjusted for sex, age, height, weight, ethnicity, duration of bisphosphonate use,
      and glucocorticoid use. Additionally, the analysis of TBS was adjusted for lumbar
      spine bone mineral density and the time difference between dual-energy X-ray
      absorptiometry scanning and the diagnosis of AFF. Patients with AFF had
      significantly higher body mass index than controls, had used bisphosphonates
      longer, and glucocorticoids and proton pump inhibitors more frequently. Sex
      specific T-score was significantly higher in patients with AFF at the lumbar
      spine (p = 0.004), but not at the femoral neck (p = 0.190) after adjustment for
      age, height, and weight. TBS did not differ significantly between patients with
      AFF and controls. Neither neck shaft angle nor any geometric variables at the
      femoral shaft measured by HSA differed between patients with AFF and controls. At
      the narrow neck, patients with AFF had lower buckling ratio and higher centroid
      position, consistent with a lower risk of classical fragility hip fractures. The
      findings at narrow neck and higher bone mineral density might be explained by the
      fact that the majority of patients with AFF used bisphosphonates to prevent
      glucocorticoid-induced osteoporosis. Based on our results, TBS and HSA do not
      appear to have value in detecting patients at risk of AFF.

PMID- 29661685
TI  - Natural Course of Local Bone Mineralization After Treatment of Benign or
      Borderline Bone Tumors and Cysts With a Composite Ceramic Bone Graft Substitute.
AB  - After surgical bone tumor removal, filling of the bone defect is frequently
      performed using a bone graft or bone graft substitute. During follow-up, precise
      quantification of changes in bone mineral density, within the treated bone
      defect, is very difficult using conventional X-ray examinations. The objectives
      of this study were to characterize the pattern of resorption/biodegradation of a
      composite calcium sulfate/hydroxyapatite bone graft substitute and to quantify
      the bone defect healing with repeated dual-energy X-ray absorptiometry (DXA)
      measurements. Seventeen patients treated for 18 benign bone lesions, with
      subsequent defect filling using 2 variants of a composite ceramic bone graft
      substitute (CERAMENTTM|BONE VOID FILLER or CERMAMENTTM|G, BONESUPPORT AB, Lund,
      Sweden), were scanned postoperatively and after 2, 6, 12, 26, and 52 wk using
      DXA. After an initial increase in bone mineral density after implantation of the
      bone graft substitute, bone mineral density decreased in the bone defect region
      throughout the 52 wk: rapidly in the first 12 wk and slower in the remaining
      weeks. Despite this continuous decrease, bone mineral density remained, on
      average, 25% higher in the operated extremity, compared with the nonoperated
      extremity, after 52 wk. The observed pattern of reduction in bone mineral density
      is consistent with the anticipated resorption of calcium sulfate within the bone
      graft substitute during the first 12 wk after surgery. We believe the DXA
      technique provides a precise method for quantification of bone graft resorption,
      but for evaluation of new bone formation, 3-dimensional imaging is needed.

PMID- 29661686
TI  - Utilization of BIA-Derived Bone Mineral Estimates Exerts Minimal Impact on Body
      Fat Estimates via Multicompartment Models in Physically Active Adults.
AB  - The purpose of this study was to compare body fat estimates and fat-free mass
      (FFM) characteristics produced by multicompartment models when utilizing either
      dual energy X-ray absorptiometry (DXA) or single-frequency bioelectrical
      impedance analysis (SF-BIA) for bone mineral content (BMC) in a sample of
      physically active adults. Body fat percentage (BF%) was estimated with 5
      compartment (5C), 4-compartment (4C), 3-compartment (3C), and 2-compartment (2C)
      models, and DXA. The 5C-Wang with DXA for BMC (i.e., 5C-WangDXA) was the
      criterion. 5C-Wang using SF-BIA for BMC (i.e., 5C-WangBIA), 4C-WangDXA (DXA for
      BMC), 4C-WangBIA (BIA for BMC), and 3C-Siri all produced values similar to 5C
      WangDXA (r > 0.99; total error [TE] < 0.83%; standard error of estimate < 0.67%;
      95% limits of agreement [LOAs] < +/-1.35%). The 2C models (2C-Pace, 2C-Siri, and
      2C-Brozek) and DXA each produced similar standard error of estimate and 95% LOAs
      (2.13%-3.12% and +/-4.15%-6.14%, respectively). Furthermore, 3C-LohmanDXA
      (underwater weighing for body volume and DXA for BMC) and 3C-LohmanBIA
      (underwater weighing for body volume and SF-BIA for BMC) produced the largest 95%
      LOAs (+/-5.94%-8.63%). The FFM characteristics (i.e., FFM density, water/FFM,
      mineral/FFM, and protein/FFM) for 5C-WangDXA and 5C-WangBIA were each compared
      with the "reference body" cadavers of Brozek et al. 5C-WangBIA FFM density
      differed significantly from the "reference body" in women (1.103 +/- 0.007 g/cm3;
      p < 0.001), but no differences were observed for 5C-WangDXA or either 5C model in
      men. Moreover, water/FFM and mineral/FFM were significantly lower in men and
      women when comparing 5C-WangDXA and 5C-WangBIA with the "reference body," whereas
      protein/FFM was significantly higher (all p <= 0.001). 3C-LohmanBIA and 3C
      LohmanDXA produced error similar to 2C models and DXA and are therefore not
      recommended multicompartment models. Although more advanced multicompartment
      models (e.g., 4C-Wang and 5C-Wang) can utilize BIA-derived BMC with minimal
      impact on body fat estimates, the increased accuracy of these models over 3C-Siri
      is minimal.

PMID- 29661687
TI  - Impact of Weight Loss With Intragastric Balloon on Bone Density and
      Microstructure in Obese Adults.
AB  - The historical concept that obesity protects against bone fractures has been
      questioned. Weight loss appears to reduce bone mineral density (BMD); however,
      the results in young adults are inconsistent, and data on the effects of weight
      loss on bone microstructure are limited. This study aimed to evaluate the impact
      of weight loss using an intragastric balloon (IGB) on bone density and
      microstructure. Forty obese patients with metabolic syndrome (mean age 35.1 +/-
      7.3 yr) used an IGB continuously for 6 mo. Laboratory tests, areal BMD, and body
      composition measurements via dual-energy X-ray absorptiometry, and volumetric BMD
      and bone microstructure measurements via high-resolution peripheral quantitative
      computed tomography were conducted before IGB placement and after IGB removal.
      The mean weight loss was 11.5%. After 6 mo, there were significant increases in
      vitamin D and carboxyterminal telopeptide of type 1 collagen levels. After IGB
      use, areal BMD increased in the spine but decreased in the total femur and the
      33% radius. Cortical BMD increased in the distal radius but tended to decrease in
      the distal tibia. The observed trabecular bone loss in the distal tibia
      contributed to the decline in the total volumetric BMD at this site. There was a
      negative correlation between the changes in leptin levels and the measures of
      trabecular quality in the tibia on high-resolution peripheral quantitative
      computed tomography. Weight loss may negatively impact bone microstructure in
      young patients, especially for weight-bearing bones, in which obesity has a more
      prominent effect.

PMID- 29661688
TI  - Effect of Positioning of the ROI on BMD of the Forearm and Its Subregions.
AB  - Inconsistent positioning of patients and region of interest (ROI) is known to
      influence the precision of bone mineral density (BMD) measurements in the spine
      and hip. However, it is unknown whether minor shifts in the positioning of the
      ROI along the shaft of the radius affect the measurement of forearm BMD and its
      subregions. The ultradistal (UD-), mid-, one-third, and total radius BMDs of 50
      consecutive clinical densitometry patients were acquired. At baseline the distal
      end of the ROI was placed at the tip of the ulnar styloid as usual, and then the
      forearm was reanalyzed 10 more times, each time shifting the ROI 1 mm proximally.
      No corrections for multiple comparisons were necessary since the differences that
      were significant were significant at p < 0.001. The UD-radius BMD increased as
      the ROI was shifted proximally; the increase was significant when shifted even 1
      mm proximally (p < 0.001). These same findings held true for the mid- and total
      radius bone density, though the percent increase with moving proximally was
      significantly greater for the UD radius than for the other subregions. However,
      there was no significant change in the one-third radius BMD when shifted
      proximally 1-10 mm. Minor proximal shifts of the forearm ROI substantially affect
      the BMD of the UD-, mid- and total radius, while having no effect on the one
      third radius BMD. Since the one-third radius is the only forearm region usually
      reported, minor proximal shifts of the ROI should not influence forearm BMD
      results significantly.

PMID- 29661689
TI  - Cardiometabolic Risk and Female Sexuality-Part II. Understanding (and Overcoming)
      Gender Differences: The Key Role of an Adequate Methodological Approach.
AB  - INTRODUCTION: Although basic science and clinical research indicate that the
      vascular physiopathology of male and female sexual dysfunction (FSD) is similar,
      to date the association between FSD and cardiovascular (CV) diseases has been
      only marginally explored. AIM: To discuss the potential reasons for differences
      in the role of CV diseases and risk factors in sexual function in women vs men in
      the 2nd part of a 2-part review. METHODS: A thorough literature search of peer
      reviewed publications on the topic was performed using the PubMed database. MAIN
      OUTCOME MEASURES: We present a review of the main factors that could account for
      this gap: (i) actual physiologic discrepancies and (ii) factors related to the
      inadequacy of the methodologic approach used to investigate CV risk in patients
      with FSD. A summary of the available methods to assess female sexual response,
      focusing on genital vascularization, is reported. RESULTS: The microanatomy and
      biochemistry of the male and female peripheral arousal response are similar; in
      contrast, there are differences in the interplay between the metabolic profile
      and sex steroid milieu, in the relative weighting of cardiometabolic risk factors
      in the pathogenesis of CV disease, and their clinical presentation and
      management. CV diseases in women are under-recognized, leading to less aggressive
      treatment strategies and poorer outcomes. Moreover, evaluation of hemodynamic
      events that regulate the female sexual response has thus far been plagued by
      methodologic problems. CONCLUSION: To clarify whether sexuality can be a mirror
      for CV health in women, the female genital vascular district should be
      objectively assessed with standardized and validated methods. Studies designed to
      establish normative values and longitudinal intervention trials on the effect of
      the treatment of CV risk factors on FSD are urgently needed. Maseroli E, Scavello
      I, Vignozzi L. Cardiometabolic Risk and Female Sexuality-Part II. Understanding
      (and Overcoming) Gender Differences: The Key Role of an Adequate Methodological
      Approach. Sex Med Rev 2018;6:525-534.

PMID- 29661690
TI  - The History of Testosterone and the Evolution of its Therapeutic Potential.
AB  - INTRODUCTION: Testosterone therapy has been controversial since its synthesis in
      the 1930s to the present day. Testosterone's history provides depth and context
      for current controversies. AIM: To review the history of testosterone therapy
      from its initial synthesis in the 1930s to the modern day. METHODS: Expert review
      of the literature. MAIN OUTCOME MEASURES: Impactful events in the history of
      testosterone. RESULTS: By the 1940s there was already a fascinating literature
      that described the many symptomatic benefits of testosterone therapy that are
      recognized today. Numerous early reports suggested testosterone therapy improved
      angina pectoris and peripheral vascular disease. The assertion by Huggins and
      Hodges (Cancer Res 1941;1:293-297) in 1941 that testosterone activated prostate
      cancer (PCa) cast a pall for the next 70 years. The introduction of the
      radioimmunoassay in the 1970s shifted the diagnosis of testosterone deficiency
      from signs and symptoms to an undue emphasis on blood test results. The fear of
      PCa was the primary obstacle to the adoption of testosterone therapy for decades.
      Prescription rates increased as accumulated evidence showed testosterone therapy
      was not associated with increased PCa risks. The observation that androgenic
      stimulation of PCa reaches a maximum at relatively low testosterone
      concentrations-the saturation model-provided the theoretical framework for
      understanding the relation between androgens and PCa and led to multiple case
      series documenting reassuring results of testosterone therapy in men with PCa.
      Recent concerns regarding cardiovascular risks also have diminished because new
      evidence suggests testosterone therapy might actually be cardioprotective. In
      2016 the Testosterone Trials provided high-quality evidence of multiple benefits
      of testosterone therapy, nearly all of which had been recognized by clinicians by
      1940. CONCLUSIONS: If the past has any lessons for the future, it is likely that
      research will continue to demonstrate health benefits of testosterone therapy,
      while it remains one of the most controversial topics in medicine. Morgentaler A,
      Traish A. The History of Testosterone and the Evolution of its Therapeutic
      Potential. Sex Med Rev 2018;X:XXX-XXX.

PMID- 29661691
TI  - Morphological and phylogenetic analyses of Rhipicephalus microplus ticks from
      Bangladesh, Pakistan and Myanmar.
AB  - Ticks of the Boophilus subgenus, classified in the genus Rhipicephalus, are
      widespread in subtropical and tropical regions, but knowledge on their
      distribution in Asia is fragmentary. The most important representatives belong to
      the Rhipicephalus (Boophilus) microplus complex, which is composed of species
      that share many morphological similarities and are therefore difficult to
      distinguish. In this study, adult Rhipicephalus (Boophilus) ticks from
      Bangladesh, Myanmar and Pakistan were subjected to phylogenetic and Scanning
      Electron Microscopy (SEM) analyses. Phylogenetic analyses of cytochrome oxidase 1
      (cox1), internal transcribed spacer 2 (ITS2) and 12S rRNA gene sequences
      confirmed that the R. microplus complex consists of at least five taxa: R.
      annulatus, R. australis, and R. microplus clades A-C. Ticks from Bangladesh,
      Myanmar and Pakistan were assigned to R. microplus clade C. SEM images revealed a
      wide range of variation in the morphology of the clade C adults, including
      morphological features previously identified as critical for distinguishing R.
      microplus from R. australis, which is illustrative for the complications in
      identifying species within the R. microplus complex using morphology only.
      Further morphological, genomic and crossbreeding studies are required to
      elucidate the species status of R. microplus clades A-C.

PMID- 29661692
TI  - Hospital ambulatory medicine: A leading strategy for Internal Medicine in Europe.
AB  - Addressing the current collision course between growing healthcare demands,
      rising costs and limited resources is an extremely complex challenge for most
      healthcare systems worldwide. Given the consensus that this critical reality is
      unsustainable from staff, consumer, and financial perspectives, our aim was to
      describe the official position and approach of the Working Group on Professional
      Issues and Quality of Care of the European Federation of Internal Medicine
      (EFIM), for encouraging internists to lead a thorough reengineering of hospital
      operational procedures by the implementation of innovative hospital ambulatory
      care strategies. Among these, we include outpatient and ambulatory care
      strategies, quick diagnostic units, hospital-at-home, observation units and
      daycare hospitals. Moving from traditional 'bed-based' inpatient care to hospital
      ambulatory medicine may optimize patient flow, relieve pressure on hospital bed
      availability by avoiding hospital admissions and shortening unnecessary hospital
      stays, reduce hospital-acquired complications, increase the capacity of hospitals
      with minor structural investments, increase efficiency, and offer patients a
      broader, more appropriate and more satisfactory spectrum of delivery options.

PMID- 29661694
TI  - Descriptive epidemiology of parkinsonism in the Canton of Geneva, Switzerland.
AB  - OBJECTIVES: A large descriptive cross-sectional population-based prevalence study
      as well as a retrospective incidence study were undertaken to ascertain the
      frequency of Parkinson's Disease (PD) and other types of degenerative and non
      degenerative parkinsonism in the Canton of Geneva, Switzerland. METHODS: An
      extensive case-finding approach including records from public hospitals, private
      neurologists and nursing homes was utilized. All patients with a diagnosis of
      parkinsonism established between 2003 and 2012 were included. Diagnosis of
      parkinsonism was ascertained by a movement disorders specialist, based on
      published and validated consensus diagnostic criteria. RESULTS: A total of 1235
      living patients with parkinsonism were identified, from which 80% presented with
      a degenerative form and 20% with a non-degenerative form of parkinsonism. Among
      the former, PD was the most frequent diagnosis (81%, age-adjusted prevalence:
      183/105 inhabitants, age-adjusted average annual incidence: 20/105/year) followed
      by dementia with Lewy bodies (9%), progressive supranuclear palsy (3.9%),
      multisystem atrophy (1.9%) and corticobasal syndrome (1.4%). Among non
      degenerative parkinsonism, drug-induced parkinsonism was the most frequent
      diagnosis (43.4%), followed by vascular parkinsonism (37%), normal pressure
      hydrocephalus (5.1%) and parkinsonism in the context of a psychiatric disorder or
      functional parkinsonism (3.8%). Crude, age-, sex-specific and age-adjusted
      prevalence and incidence of all types of parkinsonism are detailed for each
      diagnosis. CONCLUSION: This is the first Swiss population-based epidemiological
      study of PD and parkinsonism. It provides an extensive overview of the prevalence
      and incidence of degenerative and non-degenerative forms of parkinsonism. These
      data may assist clinicians with their clinical workup.

PMID- 29661693
TI  - Phosphorylation of Beta-3 adrenergic receptor at serine 247 by ERK MAP kinase
      drives lipolysis in obese adipocytes.
AB  - OBJECTIVE: The inappropriate release of free fatty acids from obese adipose
      tissue stores has detrimental effects on metabolism, but key molecular mechanisms
      controlling FFA release from adipocytes remain undefined. Although obesity
      promotes systemic inflammation, we find activation of the inflammation-associated
      Mitogen Activated Protein kinase ERK occurs specifically in adipose tissues of
      obese mice, and provide evidence that adipocyte ERK activation may explain
      exaggerated adipose tissue lipolysis observed in obesity. METHODS AND RESULTS: We
      provide genetic and pharmacological evidence that inhibition of the MEK/ERK
      pathway in human adipose tissue, mice, and flies all effectively limit adipocyte
      lipolysis. In complementary findings, we show that genetic and obesity-mediated
      activation of ERK enhances lipolysis, whereas adipose tissue specific knock-out
      of ERK2, the exclusive ERK1/2 protein in adipocytes, dramatically impairs
      lipolysis in explanted mouse adipose tissue. In addition, acute inhibition of
      MEK/ERK signaling also decreases lipolysis in adipose tissue and improves insulin
      sensitivity in obese mice. Mice with decreased rates of adipose tissue lipolysis
      in vivo caused by either MEK or ATGL pharmacological inhibition were unable to
      liberate sufficient White Adipose Tissue (WAT) energy stores to fuel
      thermogenesis from brown fat during a cold temperature challenge. To identify a
      molecular mechanism controlling these actions, we performed unbiased
      phosphoproteomic analysis of obese adipose tissue at different time points
      following acute pharmacological MEK/ERK inhibition. MEK/ERK inhibition decreased
      levels of adrenergic signaling and caused de-phosphorylation of the beta3
      adrenergic receptor (beta3AR) on serine 247. To define the functional
      implications of this phosphorylation, we showed that CRISPR/Cas9 engineered cells
      expressing wild type beta3AR exhibited beta3AR phosphorylation by ERK2 and
      enhanced lipolysis, but this was not seen when serine 247 of beta3AR was mutated
      to alanine. CONCLUSION: Taken together, these data suggest that ERK activation in
      adipocytes and subsequent phosphorylation of the beta3AR on S247 are critical
      regulatory steps in the enhanced adipocyte lipolysis of obesity.

PMID- 29661695
TI  - Acute cholecystitis induced by surgery for levodopa-carbidopa intestinal gel
      therapy: Possible relationship to pre-existing gallstones.

PMID- 29661696
TI  - Use of Highly Effective Reversible Contraception in Title X Clinics: Variation by
      Selected State Characteristics.
AB  - BACKGROUND: The use of long-acting reversible contraceptive (LARC) methods, such
      as intrauterine devices (IUDs) and implants has demonstrated high effectiveness
      in preventing pregnancy. While LARC use in Title X programs has increased over
      the past decade, little is know about the extent to which gains are occurring
      uniformly across states. METHODS: We examined state-level changes in LARC use
      among Title X clients between 2012 and 2016 using a repeated cross-sectional
      study design. States were characterized by the proportion of reproductive age
      women in need of publicly funded contraception. Variation in LARC use by level of
      need was examined using GEE models. RESULTS: Across all states, LARC use in Title
      X clinics increased from 9.1% to 16.2% during the study period. In 2012, LARC use
      in the states with the highest and lowest level of need differed by 2.3
      percentage points (7.8% compared to 10.1%). By 2015 the gap in LARC use between
      high and low need states widened to reach 5.3 percentage points, more than double
      what was observed in 2012. However, by 2016 the margin of the gap narrowed.
      CONCLUSIONS: Observed increases in LARC use among states with the highest level
      of need for publically funded services are much lower than what is observed among
      states with the lowest level of need. However, we did find this gap is narrowing.
      This finding is important given states with greater need are those with higher
      proportions of low-income and younger women who are at greater risk for
      experiencing unintended pregnancies.

PMID- 29661698
TI  - Reproductive Health Care Priorities and Barriers to Effective Care for LGBTQ
      People Assigned Female at Birth: A Qualitative Study.
AB  - BACKGROUND: Little research documents the self-identified reproductive health
      priorities and health care experiences of lesbian, gay, bisexual, transgender,
      queer (LGBTQ)-identified individuals who may be in need of services. METHODS: We
      conducted in-depth interviews with a diverse sample of 39 female-assigned-at
      birth individuals (ages 18-44) who also identified as lesbian, bisexual, queer,
      and/or genderqueer, or transmasculine. Interviews were primarily conducted in
      person in the Bay Area of California, and Baltimore, Maryland, with 11 conducted
      remotely with participants in other U.S. LOCATIONS: We asked participants about
      their current reproductive health care needs, topics they felt researchers should
      pursue, and past reproductive health care experiences. Data were analyzed using a
      framework method, incorporating deductive and inductive thematic analysis
      techniques. RESULTS: Reproductive health care needs among participants varied
      widely and included treatment of polycystic ovary syndrome and irregular menses,
      gender-affirming hysterectomies, and fertility assistance. Many faced challenges
      getting their needs met. Themes related to these challenges cross-cutting across
      identity groups included primary focus on fertility, provider lack of LGBTQ
      health competency relevant to reproductive health priorities and treatment, and
      discriminatory comments and treatment. Across themes and identity groups,
      participants highlighted that sexual activity and reproduction were central
      topics in reproductive health care settings. These topics facilitated identity
      disclosures to providers, but also enhanced vulnerability to discrimination.
      CONCLUSIONS: Reproductive health priorities of LGBTQ individuals include needs
      similar to cisgender and heterosexual groups (e.g., abortion, contraception,
      PCOS) as well as unique needs (e.g., gender affirming hysterectomies, inclusive
      safer sex guidance) and challenges in pursuing care. Future reproductive health
      research should pursue health care concerns prioritized by LGBTQ populations.

PMID- 29661697
TI  - Cardiovascular Disease Risk in Sexual Minority Women (18-59 Years Old): Findings
      from the National Health and Nutrition Examination Survey (2001-2012).
AB  - OBJECTIVE: Sexual minority women (lesbian and bisexual) experience significant
      stigma, which may increase their cardiovascular disease (CVD) risk. The purpose
      of this study was to examine the prevalence of modifiable risk factors for CVD
      (including mental distress, health behaviors, blood pressure, glycosylated
      hemoglobin, and total cholesterol) and CVD in sexual minority women compared with
      their heterosexual peers. MATERIALS AND METHODS: A secondary analysis of the
      National Health and Nutrition Examination Survey (2001-2012) was conducted.
      Multiple imputation with chained equations was performed. Logistic regression
      models adjusted for relevant covariates were run. Self-report (medical history
      and medication use) and biomarkers for hypertension, diabetes, and high total
      cholesterol were examined. RESULTS: The final analytic sample consisted of 7,503
      that included 346 sexual minority women (4.6%). Sexual minority women were more
      likely to be younger, single, have a lower income, and lack health insurance.
      After covariate adjustment, sexual minority women exhibited excess CVD risk
      related to higher rates of frequent mental distress (adjusted odds ratio [AOR],
      2.05; 95% confidence interval [CI], 1.45-2.88), current tobacco use (AOR, 2.11;
      95% CI, 1.53-2.91), and binge drinking (AOR, 1.66; 95% CI, 1.17-2.34). Sexual
      minority women were more likely to be obese (AOR, 1.61; 95% CI, 1.23-2.33) and
      have glycosylated hemoglobin consistent with prediabetes (AOR, 1.56; 95% CI, 1.04
      2.34). No differences were observed for other outcomes. CONCLUSIONS: Sexual
      minority women demonstrated increased modifiable risk factors for CVD, but no
      difference in CVD diagnoses. Several emerging areas of research are highlighted,
      in particular, the need for CVD prevention efforts that target modifiable CVD
      risk in sexual minority women.

PMID- 29661700
TI  - Correction to Lancet Diabetes Endocrinol 2018; 6: 274.

PMID- 29661699
TI  - Effect of neprilysin inhibition on renal function in patients with type 2
      diabetes and chronic heart failure who are receiving target doses of inhibitors
      of the renin-angiotensin system: a secondary analysis of the PARADIGM-HF trial.
AB  - BACKGROUND: Neprilysin inhibition has favourable effects on experimental diabetic
      nephropathy. We sought to assess the effects of neprilysin inhibition on the
      course of renal function in patients with type 2 diabetes. METHODS: In the
      randomised, double-blind PARADIGM-HF trial, the effects of sacubitril/valsartan
      (97 mg/103 mg twice daily) were compared with enalapril (10 mg twice daily) in
      8399 patients with mild-to-moderate chronic heart failure and systolic
      dysfunction. In this secondary intention-to-treat analysis, we assessed the
      change in estimated glomerular filtration rate (eGFR) over a 44-month follow-up
      period in patients with (n=3784) and those without (n=4615) diabetes. PARADIGM-HF
      is registered with ClinicalTrials.gov, number NCT01035255. FINDINGS: eGFR
      decreased by 1.1 mL/min per 1.73 m2 per year (95% CI 1.0-1.2) in patients without
      diabetes, but by 2.0 mL/min per 1.73 m2 per year (1.9-2.1) in those with diabetes
      (p<0.0001). Compared with patients treated with enalapril, those treated with
      sacubitril/valsartan had a slower rate of decline in eGFR (-1.3 vs -1.8 mL/min
      per 1.73 m2 per year; p<0.0001), and the magnitude of the benefit was larger in
      patients with versus those without diabetes (difference 0.6 mL/min per 1.73 m2
      per year [95% CI 0.4-0.8] in patients with vs 0.3 mL/min per 1.73 m2 per year
      [0.2-0.5] in those without diabetes; pinteraction=0.038). The greater effect of
      neprilysin inhibition in patients with diabetes could not be explained by the
      effects of treatment on the course of heart failure or on HbA1c. The incremental
      benefit of sacubitril/valsartan in patients with diabetes was no longer apparent
      when changes in eGFR were adjusted for urinary cyclic guanosine monophosphate
      (p=0.41). INTERPRETATION: In patients in whom the renin-angiotensin system is
      already maximally blocked, the addition of neprilysin inhibition attenuates the
      effect of diabetes to accelerate the deterioration of renal function that occurs
      in patients with chronic heart failure. FUNDING: Novartis.

PMID- 29661701
TI  - Correction to Lancet Diabetes Endocrinol 2017; 5: 680-81.

PMID- 29661702
TI  - Adolescent cancer patients' perceived quality of cancer care: The roles of
      patient engagement and supporting independence.
AB  - OBJECTIVES: A lack of focus on variation in engagement among cancer populations
      of differing developmental stages led us to examine the associations between
      patient engagement, the patient-provider relationship, cognitive development,
      readiness to transition to adulthood (transitional readiness) and perceived
      quality of care. METHODS: A sample of 101 adolescent cancer patients (diagnosed
      10-20 years) completed survey items concerning patient engagement, dimensions of
      the patient-provider relationship, cognitive development, transitional readiness,
      and demographic characteristics using an iPad/tablet during a routine clinic
      visit. RESULTS: Patient engagement was not significantly associated with
      perceived quality of care (b = .02, 95% CI: -0.06, 0.11). Instead, adolescents
      with providers that supported their independence (b = .34, 95% CI: 0.17, 0.52)
      were significantly more likely to perceive higher quality care. CONCLUSION:
      Supportive patient-provider relationships are an integral part of adolescents'
      perceptions of quality of care. Adolescents are still gaining important skills
      for navigating the medical system, and the patient-provider relationship may
      provide an important scaffolding relationship to help adolescents build
      independence in their treatment experience. PRACTICE IMPLICATIONS: Identifying
      potential mechanisms through which adolescents can provide their opinion, ask
      questions, and participate in their treatment plan will help in supporting
      adolescent independence and improve quality of care.

PMID- 29661703
TI  - Strengthening patient and family engagement in healthcare - The New Haven
      Recommendations.
AB  - OBJECTIVE: Present and discuss the development and basic structure of a
      multilevel approach to strengthen patient and family engaged care, "The New Haven
      Recommendations on partnering with patients, families and citizens to enhance
      performance and quality in health promoting hospitals and health services".
      METHODS: A generic literature review was conducted followed by a Delphi procedure
      to prepare the New Haven Recommendations. From systems theory perspective, three
      conceptual levels are used to map action areas to enhance patient and family
      engaged care. RESULTS: The recommendations propose a multilevel approach to
      enable patient, family, (and citizen representatives') involvement (a) within
      direct service provision; (b) among hospitals and health services; (c) in
      planning healthcare delivery systems and policy. CONCLUSION: The New Haven
      Recommendations provide a strategic tool and practical recommendations, which can
      be used for reflection on current practices or generating new ways of thinking
      about patient and family engaged care. They support the development of patient
      and family engaged care as core aspect of high quality healthcare, and can
      contribute to achieving the Ottawa Charter's claim of reorienting health
      services. PRACTICE IMPLICATIONS: The potential benefit of the multilevel approach
      is to reorient the basic culture of healthcare towards patient- and health
      centered care.

PMID- 29661704
TI  - Becoming an eCoach: Training therapists in online cognitive-behavioral therapy
      for chronic pain.
AB  - OBJECTIVE: Online cognitive-behavioral therapy (iCBT) is effective in supporting
      patients' self-management. Since iCBT differs from face-to-face CBT on several
      levels, proper training of therapists is essential. This paper describes the
      development and evaluation of a therapist training based on theoretical domains
      that are known to influence implementation behavior, for an iCBT for chronic
      pain. METHODS: The training consists of 1.5 days and covers the implementation
      domains "knowledge", "skills", "motivation", and "organization", by focusing on
      the therapy's rationale, iCBT skills, and implementation strategies. Using an
      evaluation questionnaire, implementation determinants (therapist characteristics,
      e-health attitude, and implementation domains) and iCBT acceptance were assessed
      among participants after training. RESULTS: Twenty-two therapists participated,
      who generally showed positive e-health attitudes, positive implementation
      expectations, and high iCBT acceptance. Organizational aspects (e.g., policy
      regarding iCBT implementation) were rated neutrally. CONCLUSIONS: An iCBT
      therapist training was developed and initial evaluations among participants
      showed favorable implementation intentions. PRACTICE IMPLICATIONS: Therapists'
      positive training evaluations are promising regarding the dissemination of iCBT
      in daily practice. Organizational support is vital and needs to be attended to
      when selecting organizations for iCBT implementation.

PMID- 29661705
TI  - Corrections.

PMID- 29661706
TI  - No one knows what tomorrow might bring.

PMID- 29661707
TI  - The genetic architecture of long QT syndrome: A critical reappraisal.
AB  - Collectively, the completion of the Human Genome Project and subsequent
      development of high-throughput next-generation sequencing methodologies have
      revolutionized genomic research. However, the rapid sequencing and analysis of
      thousands upon thousands of human exomes and genomes has taught us that most
      genes, including those known to cause heritable cardiovascular disorders such as
      long QT syndrome, harbor an unexpected background rate of rare, and presumably
      innocuous, non-synonymous genetic variation. In this Review, we aim to reappraise
      the genetic architecture underlying both the acquired and congenital forms of
      long QT syndrome by examining how the clinical phenotype associated with and
      background genetic variation in long QT syndrome-susceptibility genes impacts the
      clinical validity of existing gene-disease associations and the variant
      classification and reporting strategies that serve as the foundation for
      diagnostic long QT syndrome genetic testing.

PMID- 29661708
TI  - Editorial commentary: The caveats of cardiac imaging in Ebstein anomaly.

PMID- 29661709
TI  - Editorial commentary: Are cytokines ready for prime time? Insights from markers
      and trials.

PMID- 29661710
TI  - Editorial commentary: Nox2: A new challenge for antiplatelet treatment?

PMID- 29661711
TI  - Editorial commentary: Diagnosing spontaneous coronary artery dissection in women:
      A call for early coronary angiography.

PMID- 29661712
TI  - NADPH oxidase 2 (NOX2): A key target of oxidative stress-mediated platelet
      activation and thrombosis.
AB  - Oxidative stress represents an imbalance between the production of reactive
      oxygen species (ROS) and the cellular antioxidant system. Increased levels of
      oxidative stress contribute to the development of atherosclerosis that eventually
      leads to thrombosis; a principle cause of heart attacks and strokes. Thrombosis
      is a consequence of platelet activation and aggregate formation within the
      circulation. Platelet ROS are mostly generated by reduced nicotinamide adenine
      dinucleotide phosphate (NADPH) oxidase. NOX2 is an isoform from NADPH oxidase
      expressed in platelets and an important regulator of platelet activation
      associated thrombosis. The present article aims to highlight the relative
      contribution of NOX2 as a key target of different platelet activation pathways
      and antiplatelet treatment.

PMID- 29661713
TI  - Review with novel markers facilitates precise categorization of 41 cases of
      diagnostically challenging, "undifferentiated small round cell tumors". A
      clinicopathologic, immunophenotypic and molecular analysis.
AB  - BACKGROUND: Despite extensive immunohistochemical (IHC) and molecular studies
      combined with morphologic findings, a group of round/ovoid cell tumors
      histologically similar to Ewing sarcomas (ES) but lacking EWSR1-rearrangements
      may remain unclassifiable. DESIGN: We retrospectively analyzed 41 Ewing-like
      tumors (formalin-fixed, paraffin-embedded) previously determined as negative or
      non-informative for EWSR1-rearrangements by FISH and/or RT-PCR. A new
      histopathology revision and additional IHC and molecular analyses were carried
      out in order to investigate whether additional IHC and/or molecular testing in
      combination with the morphological findings may help in reaching a definitive
      diagnosis. RESULTS: Almost all the tumors (n=40) involved soft tissue and/or bone
      and half the patients died of disease. In the archival cases all diagnoses were
      Ewing sarcoma (ES), Ewing-like sarcoma (ELS), myoepithelial tumor and
      undifferentiated sarcoma (US). In the new review all the tumors were re
      classified as, ES (n=16), Ewing-like tumor with EWSR1 rearrangement and
      amplification and possible EWSR1-NFATC2 gene fusion (n=1), CIC-rearranged
      sarcomas or undifferentiated sarcoma, most consistent with CIC-rearranged sarcoma
      (n=7), sarcoma with BCOR-alteration or undifferentiated sarcoma, consistent with
      BCOR-associated sarcoma (n=3), neuroblastoma (n=2), unclassifiable neoplasm with
      neuroblastic differentiation (n=1), malignant rhabdoid tumor (n=2), lymphoblastic
      lymphoma (n=1), clear cell sarcoma of the gastrointestinal tract (n=1), small
      cell carcinoma (n=1), sclerosing rhabdomyosarcoma (n=1), desmoplastic small round
      cell tumor (n=1), malignant peripheral sheath nerve tumor (n=1), poorly
      differentiated synovial sarcoma (n=1), Possible gastrointestinal stromal
      tumor/GIST with predominant round cells (n=1) and possible SMARCA4-deficient
      sarcoma (n=1). NKX2.2, ETV4 and BCOR immunoreactivity was observed in all ES, CIC
      rearranged sarcomas and sarcomas with BCOR alteration, respectively. CIC
      rearrangement by FISH was observed in many of the CIC-rearranged sarcomas.
      CONCLUSION: Our analysis of 41 Ewing-like tumors confirms that there may be a
      significant pathological and IHC overlap among Ewing-like tumors, with prognostic
      and therapeutic impacts. Additional IHC (NKX2.2, ETV4 and BCOR) and molecular
      studies including FUS, CIC or BCOR analysis may support the final diagnosis when
      FISH or RT-PCR fail to detect EWSR1-rearrangements. Any molecular findings should
      always be interpreted in relation to the specific clinical and pathological
      context.

PMID- 29661714
TI  - microRNA 155 up regulation in the CNS is strongly correlated to Down's syndrome
      dementia.
AB  - This study examined the molecular correlates of Down's dementia. qRTPCR for
      chromosome 21 microRNAs was correlated with in situ hybridization,
      immunohistochemistry for microRNA targets, mRNAs located on chromosome 21, and
      neurofibrillary tangles in human and the Ts65 dn mouse Down's model. qRTPCR for
      the microRNAs on the triplicated chromosome showed miR-155 dominance in brain
      tissues (14.3 fold increase, human and 24.2 fold increase, mouse model) that co
      expressed with hyperphosphorylated tau protein. miR-155 was not elevated in
      Alzheimer's disease or neonates with Downs' syndrome. Chromosome 21 genes APP/BA
      42, DYRK1a and BACH1 were not correlated to pathologic changes in Down's
      dementia. Validated CNS targets of miR-155 that were present in controls and
      Alzheimer's disease but lacking in Down's dementia brains included BACH1,
      CoREST1, bcl6, BIM, bcl10, cyclin D, and SAPK4. It is concluded that Down's
      dementia strongly correlated with overexpression of chromosome 21 microRNA 155
      with concomitant reduction of multiple CNS-functional targets. This study
      highlights the need for anatomic pathologists to determine the specific and
      diverse pathways cells may take to form neurofibrillary tangles in the different
      dementias.

PMID- 29661716
TI  - Small cell lymphocytic variant of marginal zone lymphoma: A distinct form of
      marginal zone lymphoma derived from naive B cells as a cutaneous counterpart to
      the naive marginal zone lymphoma of splenic origin.

PMID- 29661715
TI  - Expression and clinical significance of retinoid X receptor alpha in esophageal
      carcinoma.
AB  - PURPOSE: Esophageal carcinoma (EC) is one of the most aggressive type cancers and
      dysregulation of retinoid X receptor alpha (RXRalpha) involves various tumors.
      However, the relationship of RXRalpha with the clinicopathological factors of EC,
      particularly prognostic characteristics, remains unclear. This present study was
      to evaluate the effect of RXRalpha expression in the development of EC. METHODS:
      The mRNA and protein expression level of RXRalpha in EC and normal esophageal
      tissues using reverse transcription-polymerase chain reaction (RT-PCR) and
      Western blot, respectively. The subcellular localization was detected by
      immunohistochemistry (IHC) analysis. The clinicopathological parameters were
      included age, sex, tumor size, differentiation, TNM stages and lymph node
      metastasis. Kaplan-Meier method and Cox's regression analyses were performed to
      evaluate the prognosis of 60 patients with EC. RESULTS: RXRalpha was elevated in
      EC tissues comparing with normal esophageal tissues at both mRNA and protein
      levels. The overexpression level of RXRalpha was closely associated to the tumor
      differentiation, TNM stage and lymph node metastasis of patients with EC. In
      addition, EC patients with RXRalpha high expression had significantly lower
      disease-free survival (DFS) and overall survival (OS). Multivariate analysis
      showed RXRalpha expression as an independent predictor for the DFS and OS rate of
      patients with EC. CONCLUSIONS: Our results showed that overexpression of RXRalpha
      was correlated with unfavorable prognosis, suggesting that RXRalpha may serve as
      a potential targeted therapeutic marker in the treatment of EC.

PMID- 29661717
TI  - Primary breast carcinomas with neuroendocrine features: Clinicopathological
      features and analysis of tumor growth patterns in 36 cases.
AB  - Primary breast carcinoma with neuroendocrine features (NEBC) is an uncommon
      tumor. In the classification of WHO 2012, these tumors were categorized as: 1-
      neuroendocrine tumor, well-differentiated; 2- neuroendocrine carcinoma, poorly
      differentiated/small cell carcinoma; and 3- invasive breast carcinoma with
      neuroendocrine differentiation. In this study, we reviewed NEBC except poorly
      differentiated/small cell carcinoma variant in order to define the morphological
      growth patterns and cytonuclear details of these tumors. All breast surgical
      excision materials between 2007 and 2016 were re-evaluated in terms of
      neuroendocrine differentiation. Thirty-six cases showing positive staining for
      synaptophysin and/or chromogranin A in >=50% of tumor cells were included in the
      study. All cases were female with a mean age of 67.4. Mean tumor diameter was 26
      mm. Multifocality was noted in 5 cases. Grossly, they were mostly infiltrative
      mass lesions. T stages, identified in 34 cases, were as follows: 13 cases with
      pT1; 19 pT2 and 2 pT3. We described schematically 4 types of patterns depending
      on predominant growth pattern, except one case: 1) Large-sized solid cohesive
      groups (6 cases), 2) Small- to medium-sized solid cohesive groups with
      trabeculae/ribbons and glandular structures (6 cases), 3) Mixed growth patterns
      (20 cases), 4) Invasive tumor with prominent extracellular and/or intracellular
      mucin (3 cases). The tumor cells were mostly polygonal-oval with
      eosinophilic/eosinophilic-granular cytoplasm. The nuclei of tumor cells were
      mostly round to oval with evenly distributed chromatin. Only 5 cases showed high
      grade nuclear and histological features. Molecular subtypes of the cases were as
      follows: 33 luminal A, 2 luminal B, and 1 triple negative. NEBC should come to
      mind when a tumor display one of the morphological patterns described above,
      composed of monotonous cells with mild to moderate nuclear pleomorphism and
      abundant eosinophilic/eosinophilic granular or clear cytoplasm, especially in
      elderly patients.

PMID- 29661718
TI  - The Gleason pattern 4 in radical prostatectomy specimens in current practice -
      Quantification, morphology and concordance with biopsy.
AB  - PURPOSE: The upgrading of a prostate acinar adenocarcinoma grade group 1 (GG1)
      between needle biopsy and prostatectomy is common. The extent of high-grade tumor
      and cribriform morphology are currently suggested as prognostic factors. METHODS:
      We reviewed 159 prostatectomy specimens from a private laboratory and an
      academic/public institution in Salvador, Bahia. RESULTS: Tumors signed as GG1 at
      biopsy were upgraded in 59% of all cases. These tumors showed a low frequency of
      non-focal extraprostatic extension (one case, 3%), extensive positive surgical
      margins (two cases, 6%) and seminal vesicle invasion (one case, 3%). Among GG2
      and GG3 tumors at prostatectomy, the percentage of Gleason pattern 4 (Gp4)
      involving the gland at <=1%, 2-5% and >5% was associated with extensive
      extraprostatic extension (9%, 8% and 42%, respectively) and seminal vesicle
      invasion (1%, 10% and 31%, respectively). The volume of Gp4 of <=1ml, >1 to 2ml
      and >2ml was associated with extensive extraprostatic extension (8%, 26% and 38%,
      respectively), seminal vesicle invasion (2%, 21% and 33%, respectively) and non
      focal positive surgical margins (12%, 26% and 29%, respectively). Some GG2 tumors
      (~20%) indeed showed at least one measurement of Gp4 higher than one quarter of
      GG3 carcinomas. Cribriform morphology showed no significant associations for
      other adverse pathologic prognostic factors. CONCLUSION: Upgrading from GG1 to
      GG2 is associated with a very low frequency of morphologic features associated
      with poor prognosis. Routine quantification of Gp4 is feasible in radical
      prostatectomy products and seems to better stratify tumors regarding the
      association with other morphologic parameters of prognostic importance.

PMID- 29661719
TI  - Rectal ulcer and pseudomalignant epithelial changes after prostate seed
      brachytherapy: A rare complication with a diagnostic pitfall.
AB  - BACKGROUND: Implant brachytherapy (IBT) is a well-recognized treatment modality
      for early stage prostate cancer. Rectal ulcer and rectourethral fistula
      complicating IBT may cause an alteration of the normal anatomic landmarks. In
      this context, pseudomalignant radiation-induced changes within prostatic
      epithelium may be misinterpreted as a primary rectal malignancy. Such challenging
      and misleading findings have not been described, and may not be recognized as
      such. MATERIALS AND METHODS: We present the clinical and pathologic aspects of
      two patients who underwent IBT for low stage prostate cancer that was complicated
      by deep rectal ulcer. Both patients underwent extensive palliative surgical
      resection for disease control. RESULTS: The histologic changes in both cases were
      noteworthy for extensive necrosis and inflammation of the prostate, associated
      with loss of recto-prostatic anatomical landmarks. Prostatic glands showed
      striking radiation-induced atypia and pseudomalignant epithelial changes
      extending to the rectal ulcer bed, with no residual viable tumor. The first
      patient had undergone a biopsy of the rectal ulcer bed that was misinterpreted as
      a rectal adenocarcinoma prior to surgery. The similarity between atypical glands
      of the biopsy and the benign prostatic tissue with radiation-induced atypia in
      resection specimen confirmed their benign nature. CONCLUSIONS: Deep rectal ulcer
      complicating IBT may lead to distortion of the normal recto-prostatic anatomical
      landmarks, resulting in detection of pseudo-malignant prostatic glands at the
      ulcer base. Such findings may be mistaken for a primary rectal malignancy in
      limited biopsy material if not familiar to the pathologist.

PMID- 29661720
TI  - PD-L1 immuno-expression assay in thymomas: Study of 84 cases and review of
      literature.
AB  - BACKGROUND AND AIMS: Programmed death ligand 1 (PD-L1), an immune check point
      inhibitor, is known to be expressed in several malignancies and is being
      considered as a prognostic factor and a potential immunotherapeutic target. The
      aim of this study was to characterize PD-L1 expression in thymomas and to
      determine correlation with clinicopathological features and previously published
      studies in the literature. METHODS: Tissue microarrays were prepared from
      selected blocks of thymomas and immunohistochemistry (IHC) for PD-L1 was
      performed. Cases were considered as PD-L1 positive or negative depending on
      whether the percentage of stained thymic epithelial cells were <25 or >25%.
      Results were compared clinically and with previously published studies using
      Google and Pubmed search engines. RESULTS: Of 84 cases of thymoma, 69 (82.1%)
      revealed PD-L1 positivity in >25% cells. 94.23% of type B thymoma subtypes
      (B1/B2/B3) were PD-L1 positive (P < 0.001). There was no correlation of PD-L1
      with age, gender, myasthenia gravis, the tumor size or stage of disease. Nine
      studies were available in the literature; most of which showed PD-L1 expression
      in higher stage and B subtype however percentage positivity varied from 53.7% to
      over 90%. CONCLUSIONS: PD-L1 expression is frequent in type B (B1/B2/B3)
      thymomas. It can be easily evaluated by IHC even on small biopsies in
      unresectable cases, thereby enabling improved clinical evaluation as well as
      prognostic stratification of patients. It will serve as a potential indicator for
      benefit from anti-PD-L1 antibody immunotherapy in thymomas.

PMID- 29661721
TI  - High expression of PXDN is associated with poor prognosis and promotes
      proliferation, invasion as well as migration in ovarian cancer.
AB  - BACKGROUND: Peroxidasin (PXDN) is an extracellular matrix protein with peroxidase
      activity. PXDN has been reported to participate in the processes of epithelial
      mesenchymal transition. However, the roles of PXDN in progression of cancers are
      still rare. METHODS: Expression profiles of PXDN in ovarian cancer (OC) tissues
      were obtained from GEO and TCGA database. Quantitative reverse transcription
      polymerase chain reaction (qRT-PCR) was performed to measure the expression of
      PXDN in OC cells. Kaplan-Meier method was used to analyze the overall survival of
      OC patients. Furthermore, effects of PXDN knockdown on the proliferation,
      invasion as well as migration of HEY cells were examined by Cell Counting kit-8
      (CCK-8), wound healing and transwell assay. Additionally, western blot assay was
      conducted to detect the levels of several key proteins in PI3K/Akt pathway.
      RESULTS: PXDN was highly expressed in OC tissues and cells. OC Patients with high
      PXDN expression showed poorer overall survival rate compared to the OC patients
      with low PXDN expression. The results of the present study demonstrated that
      knockdown of PXDN significantly suppressed the proliferation, invasion and
      migration of HEY cells. In addition, after silencing PXDN in HEY cells, the
      expression levels of the key protein phosphorylation in PI3K/Akt pathway were
      obviously decreased, including p-PI3K and p-Akt, that resulting in the inhibition
      of PI3K/Akt pathway activation. CONCLUSION: PXDN might play a promoter role in
      the proliferation, invasion and migration of OC cells through regulating the
      activation of PI3K/Akt pathway. Therefore, PXDN might be regarded as a potential
      target for OC therapy.

PMID- 29661722
TI  - The knockdown of the mediator complex subunit MED30 suppresses the proliferation
      and migration of renal cell carcinoma cells.
AB  - BACKGROUND: The mediator complex consists of 33 subunits and plays a central role
      in transcription. Studies have already described the involvement of individual
      subunits, especially in carcinogenesis. With regard to the subunit MED30, this
      has, so far, only been confirmed in gastric and breast carcinoma. The role of
      MED30 in urological tumours is unknown. MATERIALS AND METHODS: First, a database
      analysis using cBioPortal was performed for the mRNA expression and survival
      analysis of MED30 in clear cell renal cell carcinoma (ccRCC) and papillary RCC
      (pRCC). The immunohistochemical analysis (IHC) against MED30 was performed on
      tissue microarrays (TMA), with benign, ccRCC, pRCC samples, and ccRCC-metastases.
      Intensity evaluation was performed using the IRS (Immunoreactive Score). The
      ccRCC cell lines ACHN and A-498 were used for the functional investigation of
      proliferation, migration, and invasion after the knockdown of MED30 by siRNA.
      RESULTS: In a database analysis by cBioPortal, it was shown that mRNA
      overexpression of MED30 in the pRCC was significantly associated with a poorer
      overall survival and progression-free survival. In the IHC, pRCC showed the
      highest level of MED30 expression, unfortunately without significant results in
      the survival analysis. The knockdown of MED30 resulted in a significant decrease
      in proliferation, migration, and invasion in ccRCC. CONCLUSION: In summary, MED30
      seems to be involved in the progression of the RCC.

PMID- 29661723
TI  - High levels of intratumor heterogeneity characterize the expression of epithelial
      mesenchymal transition markers in high-grade clear cell renal cell carcinoma.
AB  - Immunohistochemistry is a basic routine in establishing the diagnosis of many
      tumors. However, immunomarkers are often irregularly distributed across different
      regions of the same tumor, alternating positive and negative areas without any
      apparent cause. Full identification of this type of intratumor heterogeneity is
      crucial for patients since the expression of many markers is linked to the
      prognosis and/or treatment of some tumors. We have quantified this variability
      testing 406 tumor samples from eight clear cell renal cell carcinomas using four
      epithelial-mesenchymal transition markers (vimentin, ZEB-1, beta-catenin, and E
      cadherin) and two different sampling protocols. Routine sampling included an
      amount of 59 samples (average, 7.3 samples/case) and multisite tumor sampling did
      a total of 347 samples (average, 43.3 samples/case). High variability of
      immunostaining was detected with E-cadherin and ZEB-1 in all high-grade cases.
      Irregular patterns of expression were detected in all tumors including all
      histologically homogeneous low-grade tumors. Multisite tumor sampling protocol
      detected a significant decreased number of E-cadherin, beta-catenin and ZEB-1
      positive samples in high-grade tumors. We conclude that high levels of intratumor
      heterogeneity characterize the immunohistochemical expression of epithelial
      mesenchymal transition markers in high-grade clear cell renal cell carcinomas.
      Multisite tumor sampling protocol outperforms routine sampling in detecting
      immunohistochemical intratumor heterogeneity.

PMID- 29661724
TI  - Variation in nuclear size and PD-L2 positivity correlate with aggressive
      chromophobe renal cell carcinoma.
AB  - Chromophobe renal cell carcinoma (CRCC) is not amenable to International Society
      for Urologic Pathology-endorsed nucleolar grading. Novel grading approaches were
      proposed, but the rarity of adverse pathology hampers their discriminatory value.
      We investigate simple linear micrometer measurements and a proposed immunostain
      in CRCCs. 32 patients' CRCCs were studied: 12 adverse cases (stage pT3,
      recurrence, or metastasis), 15 controls (stage <=pT2, no recurrence or metastasis
      after >3 years), and 8 metastases (3 were paired with primary adverse cases). The
      ratio of greatest dimensions of largest and smallest nuclei, in each of 5 "worst"
      high-power fields, excluding those with degenerative features, was designated
      variation in nuclear size (VNS). Percent multinucleate cells (PMC) were also
      counted. Mouse anti PD-L2 monoclonal antibody immunostaining was performed. Mean
      VNS measured in adverse primary and control primary tumors were 3.7 +/- 0.5 and
      2.4 +/- 0.4 respectively (P < .001), and 3.4 +/- 0.4 for metastases (P < .001).
      Optimal VNS cut-off was 2.5, with sensitivity and specificity 0.85 and 0.81,
      respectively. PMCs were 6.0 +/- 3.0 for adverse group, 5.7 +/- 2.7 for controls,
      and 4.1 +/- 1.6 for metastases (P = NS). PD-L2 could not discriminate adverse
      versus good primary tumors (chi21.6, P = .2), but was higher in metastases (chi2
      6.9, P < .01), or metastases plus adverse primary tumors (chi2 4.8, P = .03),
      compared to good-pathology primary tumors. In conclusion, VNS is an easily
      obtained measurement that can predict adverse behavior of chromophobe RCC, and
      may impart value for needle biopsy reporting and the choice of active
      surveillance. PD-L2 was elevated in metastases but was less useful for primary
      tumors.

PMID- 29661725
TI  - Importin-beta and exportin-5 are indicators of acute viral infection: Correlation
      of their detection with commercially available detection kits.
AB  - This work focused on immunohistochemistry markers of acute viral infections.
      Viral infected cells were detected by in situ based methods (reovirus, rabies
      virus) or cytologic changes (human papillomavirus, molloscum contagiosum virus,
      herpes simplex virus). Two proteins involved in nuclear trafficking, importin
      beta and exportin-5, were detected in the infected cells for each virus and not
      in the control tissues. A wide variety of other proteins, including caspase-3,
      and bcl-2 family members (bcl2, bclX, MCL1, BAK, BAX, BIM, BAD) showed wide
      variations in expression among the different viral infections. Specificity of the
      importin-beta and exportin-5 signals varied greatly with different commercially
      available peroxidase conjugates. It is concluded that immunohistochemistry
      detection of importin-beta and exportin-5 may be useful markers of acute viral
      infection, which suggests that increased nuclear trafficking may be an important
      concomitant of viral proliferation.

PMID- 29661726
TI  - Detection of synchronous primary lung adenocarcinomas with genomic sequencing.
AB  - In the setting of synchronous pulmonary carcinomas, distinguishing between a
      monoclonal process with intrapulmonary metastasis and two independent tumors has
      significant therapeutic and prognostic implications. We describe two cases in
      which molecular profiling was used to characterize synchronous, primary pulmonary
      tumors and guide clinical management. In both cases, the patients underwent
      surgical resection without adjuvant chemotherapy or radiation and remain free of
      disease.

PMID- 29661727
TI  - Investigation of the relationship of Epstein-Barr virus with in situ
      hybridization in renal-cell carcinomas.

PMID- 29661728
TI  - Overexpression of COX2 indicates poor survival in urothelial bladder cancer.
AB  - BACKGROUND: COX2 is a cyclo-oxygenase enzyme expressed in the tumor cells,
      inflammatory cells, stromal and non-epithelial cells. The study was conducted to
      evaluate the expression of COX2 in Urothelial carcinoma and find the association
      with progression and recurrence. METHODS: The expression of COX2 was evaluated by
      real-time PCR and immunohistochemistry. RESULTS: Gene expression of COX2 was
      found to be upregulated >28-fold in urothelial cancer compared to adjacent normal
      bladder mucosa. Inflammatory cell expression of COX2 was found in 92% cases
      whereas only 37% cases showed COX2 overexpression in tumor cells. Tumor cell COX2
      overexpression was significantly associated with invasion and recurrence.
      CONCLUSION: COX2 expression is a marker of invasion, recurrence and poor survival
      and may have a role in predicting the cases which will benefit from additional
      treatment with COX2 inhibitors in urothelial carcinoma.

PMID- 29661729
TI  - Myositis ossificans - Another condition with USP6 rearrangement, providing
      evidence of a relationship with nodular fasciitis and aneurysmal bone cyst.
AB  - Myositis ossificans is defined as a self-limiting pseudotumor composed of
      reactive hypercellular fibrous tissue and bone. USP6 rearrangements have been
      identified as a consistent genetic driving event in aneurysmal bone cyst and
      nodular fasciitis. It is therefore an integral part of the diagnostic workup when
      dealing with (myo)fibroblastic lesions of soft tissue and bone. Two cases of
      myositis ossificans with USP6 rearrangement were published so far. We determine
      herein the incidence of USP6 rearrangement in myositis ossificans using USP6
      fluorescence in situ hybridization analysis (FISH). Of the 11 cases included,
      seven patients were female and four were male. Age ranged from 6 to 56 years
      (mean 27 years). Lesions were located in the thigh (n = 5), knee (n = 1), lower
      leg (n = 1), lower arm (n = 1), perineum (n = 1), gluteal (n = 1) and thoracic
      wall (n = 1). All assessable cases except one (8/9) showed rearrangement of USP6
      providing evidence that myositis ossificans is genetically related to nodular
      fasciitis and aneurysmal bone cyst.

PMID- 29661730
TI  - Distribution of lymphoid neoplasms in Northwest China: Analysis of 3244 cases
      according to WHO classification in a single institution.
AB  - To explore the distribution of lymphoid neoplasms in Northwest China, the
      clinical and pathological data of lymphoma patients from 2006 to 2014 were
      analyzed according to the WHO classification in Xijing Hospital. Of the 3244
      cases, mature B-cell neoplasms occupied 60.7%, while mature T/NK-cell neoplasms
      and Hodgkin's lymphomas (HL) occupied 26.2% and 8.1%, respectively. The most
      common subtype of lymphoma was diffuse large B-cell lymphoma (35.0%), followed by
      extranodal NK/T-cell lymphoma, nasal type (ENKTCL) (12.9%) and marginal zone B
      cell lymphoma (7.8%). Mixed cellularity (34.0%) was the most common subtype of
      HL. The especially high proportion of ENKTCL was the most outstanding feature of
      our study in comparison to previous reports. The mean age of all lymphoid
      neoplasms cases was 51years and most subtypes showed male predominance, with an
      average male-female ratio of 1.6. Extranodal lymphomas took up about 60% of all
      cases and gastrointestinal tract was the most frequently involved site. In
      conclusion, the distribution of lymphoid neoplasms of Northwest China showed some
      features similar to previous reports of China and other countries, but some
      subtypes presented distinct features.

PMID- 29661731
TI  - Myofibroblasts and mast cells: influences on biological behavior of odontogenic
      lesions.
AB  - Odontogenic lesions differ in their rate of recurrence and aggressiveness. This
      study aimed to evaluate the presence of myofibroblasts and mast cells in
      odontogenic lesions. Sample consisted of 20 cases each of dentigerous cysts,
      odontogenic keratocysts, and solid ameloblastomas. Histologic sections were
      submitted to immunohistochemistry using anti-alpha-smooth muscle actin and anti
      tryptase antibodies. Myofibroblasts and mast cells were counted at *400
      magnification in 5 and 10 fields, respectively. Myofibroblasts were more frequent
      in ameloblastomas (24.41), followed by odontogenic keratocysts (16.21) and
      dentigerous cysts (11.85; P=.002). Granulated and degranulated mast cells were
      more frequent in dentigerous cysts (7.88 and 8.96, respectively), followed by
      odontogenic keratocysts (6.53 and 7.08) and ameloblastomas (5.21 and 1.88). The
      difference was only significant for degranulated mast cells (P<.05). Analysis of
      the correlation between myofibroblasts and mast cells (granulated and
      degranulated) revealed a moderate positive correlation only in ameloblastomas
      (R=0.621, P=.003). Probably, myofibroblasts are related to the biological
      behavior of the odontogenic lesions studied, particularly their aggressiveness.
      On the other hand, mast cells seem to be associated with inflammatory processes,
      which are more frequent in cystic lesions than in benign neoplasms. In addition,
      mast cells may induce the differentiation of fibroblasts into myofibroblasts,
      thus increasing the number of the latter.

PMID- 29661732
TI  - MCM-2 expression differentiates potentially malignant verrucous lesions from oral
      carcinomas.
AB  - BACKGROUND: Mcm-2 is a biomarker belonging to Mcm family of proteins which has
      rarely been used in oral potentially malignant and malignant lesions of the
      verrucous type. The objective of this study is to assess the expression of Mcm-2
      in Normal Oral Mucosa (NM), Verrucous Hyperplasia (VH), Verrucous Carcinoma (VC)
      and Oral Squamous Cell Carcinoma (OSCC) and compare it with the
      clinicopathological characteristics. METHODOLOGY: A total of 70 formalin fixed
      paraffin embedded tissue samples (10 cases of Normal Mucosa NM- Group A, 10 cases
      of Verrucous Hyperplasia- VH without Dysplasia- Group B, 10 cases of Verrucous
      Hyperplasia- VH with Dysplasia- Group C, 20 cases of Verrucous Carcinoma VC-Group
      D, 20 cases of Oral Squamous Cell Carcinoma OSCC- Group E) were subjected to
      immunohistochemistry with Mcm-2 antibody. Statistical analysis was carried out
      with various tests like ANOVA, Tukey HSD, Chi-Square and Shapiro-Wilk test by
      using the SPSS software. RESULTS: There was a significant difference in Mcm-2
      expression with quantitative analysis among all the groups (p < 0.05). There was
      a significant progressive increase in nuclear Labelling Indices (nLI) from NM
      (49.08%), VC (60.45%), VH with Dysplasia (64.10%), and OSCC (89.22%). CONCLUSION:
      The findings suggest that Mcm-2 may be a sensitive proliferation marker in oral
      potentially malignant and malignant lesions which may be useful for
      differentiating between VH with/ without dysplasia, VC and OSCC.

PMID- 29661734
TI  - Pathology resident perspectives about early autopsy experiences.
AB  - The performance of autopsies remains an integral part of residency training in
      Anatomic Pathology. A number of medical schools no longer require an autopsy
      experience; therefore, a subset of pathology residents has never seen an autopsy
      performed prior to commencement of residency training. Although much as been
      written regarding student's perspectives on their medical school anatomy
      experiences, practically nothing has been written about resident perspectives on
      the autopsy experience. Surveys were sent to all Pathology resident trainees (n =
      27) in a training program exploring resident perspectives on their early autopsy
      experiences. Of the 13 residents who completed the survey, ten indicated a
      discomfort level of 3 or 4 (Likert scale of 1-5 with 1 = no discomfort and 5 =
      very uncomfortable) associated with their first autopsy; the most commonly cited
      reasons included discomfort with odors/body fluids (n = 6), fear of making a
      mistake (n = 5), and uncertainty about what to do (n = 4). Six residents felt it
      would be worthwhile to engage in a discussion around the first autopsy experience
      to help process it. In summary, a subset of residents experience discomfort
      around their first autopsy experience. Sensitivity to and acknowledgement of this
      discomfort and an opportunity to vet feelings and concerns should be considered
      as part of Pathology residency education.

PMID- 29661733
TI  - Analysis of EML4-ALK rearrangement in non-small cell lung cancer in Argentina.
AB  - INTRODUCTION: Identification of EML4-ALK rearrangement by FISH test has become
      standard in advanced NSCLC patients. There is limited information about the
      prevalence and clinical characteristics of ALK translocation in Latin America.
      The aim of our study was to evaluate this lung cancer subtype features in
      Argentinian patients and the factibility of FISH test with different methods used
      for obtaining tissue samples. METHODS: Between August 2014 and February 2017, 183
      non-squamous NSCLC patients were prospectively enrolled from five Argentinian
      institutions. Different techniques and procedures were used to obtained tissue
      samples material. ALK determination was performed by FISH and
      immunohistochemistry (IHC). Correlation with clinico-pathological information and
      different biopsy procedures was assessed. RESULTS: From 183 non-squamous NSCLC
      samples, 131 could perform FISH test, finding 123 (93.9%) negative and 8 (6.1%)
      positive patients. Fifty-one samples were not evaluable by FISH, 35 because of
      technical problems and 16 due to not/weak signal. The difficulties in obtaining
      adequate FISH tests were observed significantly more frequently for fine-needle
      aspiration (FNA) and core-needle biopsy than for excisional and incisional biopsy
      (p = 0.009). Regarding the procedures, surgery was the most efficient, obtaining
      only 12.7% (10/79) of not evaluable samples for FISH, while CT guided biopsy and
      transbronchial biopsy (TBB) failed in 43.8% (21/48) and 41.3% (19/46) of patients
      respectively (p < 0.001). We observed a significant association between ALK
      translocation and never smoking habit (p = 0.004). CONCLUSION: Our ALK
      rearrangements frequency (6.1%) was similar to the reports worldwide. One of the
      major determinants for the ALK FISH test success is the quality of the tissue
      sample obtained.

PMID- 29661735
TI  - Fine needle aspiration of alveolar soft part sarcoma in a child:
      Cytomorphological clues for the surgical pathologist.
AB  - Alveolar soft part sarcoma (ASPS) is a rare soft tissue neoplasm generally
      affecting adolescents and young adults. Its unique histologic and ultrastructural
      features have been well-described; however, the cytopathological features of ASPS
      are less well-characterized, and recognition of this entity's features on
      cytologic preparations can ensure that the specimen adequacy and
      appropriate/rapid tissue allocation for additional testing. Herein we report a
      FNA case of ASPS with emphasis on cytomorphologic characteristics.

PMID- 29661736
TI  - Loss of PD-L1 (SP-142) expression characterizes renal vein tumor thrombus
      microenvironment in clear cell renal cell carcinoma.
AB  - Immunotherapy is a promising tool in the treatment of patients with advancer
      renal cancer, in particular the blockage of immune checkpoint inhibitors. Clear
      cell renal cell carcinoma is an example of heterogeneous neoplasm and this
      particular characteristic is responsible of many therapeutic failures so far.
      Since variations in the local microenvironment across a tumor may conditionate
      the effect of this new therapy, a deeper knowledge of this issue seems advisable
      for any treatment success. We have analyzed the PD-L1 (SP142) expression in three
      different areas in the tumor and in two areas in the renal vein/caval thrombi in
      39 advanced clear cell renal cell carcinomas to determine the extent and
      potential clinical significance of this regional variability. A statistically
      significant decrease in PD-L1 expression has been detected between the main tumor
      and its thrombus faction (p < 0.0001). Also, we have observed a high variability
      in the PD-L1 positivity across the three different areas of the main tumor
      tested, with only three cases being uniformly positive in all tested areas. In
      conclusion, PD-L1 expression display a highly variable distribution in clear cell
      renal cell carcinomas and this particularity should be kept in mind when
      selecting the tumor samples to be tested for immunotherapy.

PMID- 29661737
TI  - A rapid triage protocol to optimize cold ischemic time for breast resection
      specimens.
AB  - Prolonged time from specimen excision to adequate formalin exposure, or cold
      ischemic time (CIT), negatively impacts estrogen receptor (ER), progesterone
      receptor (PR) and HER-2 biomarker studies routinely performed on breast
      specimens. Current guidelines recommend CIT of <=1 h. Since formalin penetrates
      resections slowly, optimal fixation requires incision. We evaluated the efficacy
      of a rapid triage protocol developed to optimize CIT. We identified 2821
      specimens: 650 (23.0%) excisional biopsies (EB), 1051 (37.3%) lumpectomies, and
      1120 (39.7%) mastectomies. CIT was available for 2362 (83.7%), with 1845 (78.1%)
      <=1 h and 2323 (98.3%) <=4 h. IHC was performed in 533/2821 (18.9%) and was
      associated with lumpectomy and mastectomy procedures when compared to EB.
      However, IHC was also performed on 11.1% (72/650) of EB specimens despite EB
      being significantly less likely to have CIT recorded (468/650; 72% for EB vs.
      1894/2171; 87.2% for lumpectomies/mastectomies). Our study highlights the need
      for rapid triage of breast resections with known or suspected malignant diagnoses
      and outlines our procedure for optimizing CIT. Additionally, we advocate treating
      ALL breast resections as having the potential of being malignant and requiring
      biomarker studies for which optimal CIT is of great importance.

PMID- 29661738
TI  - Overexpression of Lox in triple-negative breast cancer.
AB  - BACKGROUND: Triple negative breast cancer (TNBC) accounts for approximately 15%
      of breast cancers. It is associated with a poor prognosis and typically earlier
      onset of metastasis in comparison with other breast cancer subtypes. Since TNBC
      lacks the expression of estrogen and progesterone receptors and Her2 status is
      also negative, there is currently no target that can be used for systemic
      therapy. Epithelial-mesenchymal transition (EMT) plays an important role in tumor
      progression and metastasis. In this study, we examined a subset of EMT markers
      consisting of Snail, Twist-1 and Lox in TNBC and non-TNBC breast cancer subtypes
      and analyzed their expression pattern in regard to subtype, clinico-pathological
      parameters and prognosis. EXPERIMENTAL DESIGN: We analyzed 659 breast cancer
      samples from two tissue microarrays. Breast cancer samples were categorized into
      two groups according to hormone receptor expression and Her2 status (n = 146 were
      triple negative, n = 513 were non triple-negative). Immunohistochemical
      expression of Snail, Twist-1 and Lox was semi-quantitatively analyzed using a
      three-tiered (weak-moderate-strong) scoring system. Results were statistically
      analyzed and correlated to clinico-pathological parameters and overall survival.
      RESULTS: Strong overexpression of Lox was significantly higher in triple negative
      breast cancers when compared to non triple-negative breast cancers (p < 0.001).
      No difference was seen between the groups regarding Snail and Twist expression (p
      > 0.05). In addition, Lox expression was significantly stronger in poorly
      differentiated (G3) breast cancers (p < 0.001 for Lox). CONCLUSIONS: The EMT
      marker Lox has a differential expression pattern in breast cancer, being
      significantly overexpressed in triple negative breast cancers. We could not link
      this expression to prognosis, however, this marker might be explored in future
      studies as possible target for systemic therapy of TNBC.

PMID- 29661739
TI  - Eosinophilic Fasciitis in Association With Hypereosinophilic Syndrome in an HIV
      Infected Patient With Severe Multiorgan Involvement.

PMID- 29661740
TI  - Tolerability and Immunological Effect of Short Up-Dosing Immunotherapy With 2
      Standardized Native Allergen Extracts Derived From the Pollen of Salsola kali and
      Cupressus arizonica.

PMID- 29661741
TI  - Recall Urticaria: Aspirin Also Induces It.

PMID- 29661742
TI  - Overlap Between DRESS Syndrome and Exanthema Induced by Sulfadiazine in a Patient
      Treated With Sulfamethoxazole: Utility of the Lymphocyte Transformation Test for
      Identification of the Culprit Drug.

PMID- 29661743
TI  - Anaphylaxis to Etoricoxib.

PMID- 29661744
TI  - Allergy To Limanda aspera (Yellowfin Sole): Report of a Case of Food Allergy in a
      Child.

PMID- 29661745
TI  - Evolution of analgesic prescriptions in ambulatory care patients aged 75 and
      over, three months after a hospitalization in geriatric medicine.
AB  - The main objective is to analyze the evolution of analgesic treatment three to
      five months after a hospitalization in geriatric medicine for patients aged 75
      and over, considering the influences of various factors and reasons of
      modifications. In this single institution and cohort study, patients were
      included from geriatric medicine at the University Hospital of Caen. Analgesic
      treatments were collected during hospitalization. Three months post
      hospitalization, general practitioners were contacted regarding the evolution of
      the analgesic treatment. Patients included were hospitalized between June and
      September 2015. Three months after hospitalization, 75 patients had useful data.
      There were changes of treatment for 58.7 % of patients (n=44), most of whom had a
      reduction of treatment (n=23). The main cause for change was the occurrence of an
      intercurrent event, 34.1 % (n=15), in particular a new hospitalization (n=11),
      and pain improvement : 31.9 % (n=14). The presence of tramadol on discharge
      prescriptions was an influent factor of the treatment change three months post
      hospitalization. After a hospitalization, general practitioners have an important
      role in the necessary adaptation of pain treatment in the patient's everyday
      life.

PMID- 29661746
TI  - Effects of oral vitamin D3 supplementation in stage 3 chronic kidney disease
      subjects: insulin resistance syndrome and hormonal disturb interactions.
AB  - The 1-25-hydroxyvitamine D (1-25OHD) or calcitriol deficiency in chronic kidney
      disease (CKD) patients was associated with increases vascular calcification risk,
      nephrons reduction, bone deficit and cardiovascular mortality by atherosclerosis.
      The objective of this study was to investigate the pleiotropic effects of 200.000
      IU (D200 group) every 3 months versus 30.000 IU (D30 group) every month dose
      vitamin D supplementation in stage 3 CKD patients. A cohort of 132 adult subjects
      was randomized into 2 groups according to dose vitamin D supplementation in
      deficient subjects (25OHD <50 nmol/L or <20 ng/mL). Serum 25OHD levels were
      assessed before and after 6 and 12 months of vitamin D supplementation. Patients
      were phenotyped for IRS according to NCEP/ATPIII. Glomerular filtration rate
      (GFR) by the MDRD formula. Insulin resistance was evaluated by the Homa-IR model.
      IRS clusters by Cobas Integra 400(r). PTH, Cortisol and IGF-1 were determined by
      radioimmunologic methods. The 25OHD profile was analyzed by LC-MS/MS. Results
      showed that vitamin D supplementation increased serum 25OHD concentrations (>75
      nmol/L or >30 ng/mL) in both groups; however, the supplementation benefits are
      more significant in D30 group than in D200 group. We noted a highlighted
      improvement of kidney function, an inhibition of GFR collaps, a safe reduction of
      proteinuria, a significant PTH and C-reactive protein (inflammation) levels
      attenuation, concomitantly with cortisolemia normalization and decreased IGF-1
      depletion. Nevertheless, homocysteine and Lp(a) concentrations remain increased,
      not modulated by vitamin D treatment. This study shows that continuous low doses
      (30.000 IU every month) are recommended for intermittent high doses (200.000 IU
      every 3 months) vitamin D supplementation. Our study suggests that the serum
      25OHD profile can be considered a reliable biomarker in the bioclinic CKD status
      to stage stabilization and inhibit its evolution.

PMID- 29661747
TI  - Patient Continued Use of Online Health Care Communities: Web Mining of Patient
      Doctor Communication.
AB  - BACKGROUND: In practice, online health communities have passed the adoption stage
      and reached the diffusion phase of development. In this phase, patients equipped
      with knowledge regarding the issues involved in health care are capable of
      switching between different communities to maximize their online health community
      activities. Online health communities employ doctors to answer patient questions,
      and high quality online health communities are more likely to be acknowledged by
      patients. Therefore, the factors that motivate patients to maintain ongoing
      relationships with online health communities must be addressed. However, this has
      received limited scholarly attention. OBJECTIVE: The purpose of this study was to
      identify the factors that drive patients to continue their use of online health
      communities where doctor-patient communication occurs. This was achieved by
      integrating the information system success model with online health community
      features. METHODS: A Web spider was used to download and extract data from one of
      the most authoritative Chinese online health communities in which communication
      occurs between doctors and patients. The time span analyzed in this study was
      from January 2017 to March 2017. A sample of 469 valid anonymous patients with
      9667 posts was obtained (the equivalent of 469 respondents in survey research). A
      combination of Web mining and structural equation modeling was then conducted to
      test the research hypotheses. RESULTS: The results show that the research
      framework for integrating the information system success model and online health
      community features contributes to our understanding of the factors that drive
      patients' relationships with online health communities. The primary findings are
      as follows: (1) perceived usefulness is found to be significantly determined by
      three exogenous variables (ie, social support, information quality, and service
      quality; R2=0.88). These variables explain 87.6% of the variance in perceived
      usefulness of online health communities; (2) similarly, patient satisfaction was
      found to be significantly determined by the three variables listed above
      (R2=0.69). These variables explain 69.3% of the variance seen in patient
      satisfaction; (3) continuance use (dependent variable) is significantly
      influenced by perceived usefulness and patient satisfaction (R2=0.93). That is,
      the combined effects of perceived usefulness and patient satisfaction explain
      93.4% of the variance seen in continuance use; and (4) unexpectedly, individual
      literacy had no influence on perceived usefulness and satisfaction of patients
      using online health communities. CONCLUSIONS: First, this study contributes to
      the existing literature on the continuance use of online health communities using
      an empirical approach. Second, an appropriate metric was developed to assess
      constructs related to the proposed research model. Additionally, a Web spider
      enabled us to acquire objective data relatively easily and frequently, thereby
      overcoming a major limitation of survey techniques.

PMID- 29661748
TI  - Virtual Reality Cue Refusal Video Game for Alcohol and Cigarette Recovery
      Support: Summative Study.
AB  - BACKGROUND: New technologies such as virtual reality, augmented reality, and
      video games hold promise to support and enhance individuals in addiction
      treatment and recovery. Quitting or decreasing cigarette or alcohol use can lead
      to significant health improvements for individuals, decreasing heart disease risk
      and cancer risks (for both nicotine and alcohol use), among others. However,
      remaining in recovery from use is a significant challenge for most individuals.
      OBJECTIVE: We developed and assessed the Take Control game, a partially immersive
      Kinect for Windows platform game that allows users to counter substance cues
      through active movements (hitting, kicking, etc). METHODS: Formative analysis
      during phase I and phase II guided development. We conducted a small wait-list
      control trial using a quasi-random sampling technique (systematic) with 61
      participants in recovery from addiction to alcohol or tobacco. Participants used
      the game 3 times and reported on substance use, cravings, satisfaction with the
      game experience, self-efficacy related to recovery, and side effects from
      exposure to a virtual reality intervention and substance cues. RESULTS:
      Participants found the game engaging and fun and felt playing the game would
      support recovery efforts. On average, reported substance use decreased for
      participants during the intervention period. Participants in recovery for alcohol
      use saw more benefit than those in recovery for tobacco use, with a statistically
      significant increase in self-efficacy, attitude, and behavior during the
      intervention. Side effects from the use of a virtual reality intervention were
      minor and decreased over time; cravings and side effects also decreased during
      the study. CONCLUSIONS: The preliminary results suggest the intervention holds
      promise as an adjunct to standard treatment for those in recovery, particularly
      from alcohol use.

PMID- 29661749
TI  - A Website Supporting Sensitive Religious and Cultural Advance Care Planning
      (ACPTalk): Formative and Summative Evaluation.
AB  - BACKGROUND: Advance care planning (ACP) promotes conversations about future
      health care needs, enacted if a person is incapable of making decisions at end-of
      life that may be communicated through written documentation such as advance care
      directives. To meet the needs of multicultural and multifaith populations in
      Australia, an advance care planning website, ACPTalk, was funded to support
      health professionals in conducting conversations within diverse religious and
      cultural populations. ACPTalk aimed to provide religion-specific advance care
      planning content and complement existing resources. OBJECTIVE: The purpose of
      this paper was to utilize the context, input, process, and product (CIPP)
      framework to conduct a formative and summative evaluation of ACPTalk. METHODS:
      The CIPP framework was used, which revolves around 4 aspects of evaluation:
      context, input, process, and product. Context: health professionals' solutions
      for the website were determined through thematic analysis of exploratory key
      stakeholder interviews. Included religions were determined through an
      environmental scan, Australian population statistics, and documentary analysis of
      project steering committee meeting minutes. Input: Project implementation and
      challenges were examined through documentary analysis of project protocols and
      meeting minutes. Process: To ensure religion-specific content was accurate and
      appropriate, a website prototype was built with content review and functionality
      testing by representatives from religious and cultural organizations and other
      interested health care organizations who completed a Web-based survey. Product:
      Website analytics were used to report utilization, and stakeholder perceptions
      were captured through interviews and a website survey. RESULTS: Context: A total
      of 16 key stakeholder health professional (7 general practitioners, 2 primary
      health nurses, and 7 palliative care nurses) interviews were analyzed. Website
      solutions included religious and cultural information, communication ideas, legal
      information, downloadable content, and Web-based accessibility. Christian and non
      Christian faiths were to be included in the religion-specific content. Input:
      Difficulties gaining consensus on religion-specific content were overcome by
      further state and national religious organizations providing feedback. Process: A
      total of 37 content reviewers included representatives of religious and cultural
      organizations (n=29), health care (n=5), and community organizations (n=3). The
      majority strongly agree or agree that the content used appropriate language and
      tone (92%, 34/37), would support health professionals (89%, 33/37), and was
      accurate (83%, 24/29). Product: Resource usage within the first 9 months was
      12,957 page views in 4260 sessions; majority were (83.45%, 3555/4260) from
      Australia. A total of 107 Australian-based users completed the website survey;
      most felt information was accurate (77.6%, 83/107), easy to understand (82.2%,
      88/107), useful (86.0%, 92/107), and appropriate (86.0%, 92/107). A total of 20
      nurses (general practice n=10, palliative care n=8, and both disciplines n=2)
      participated in stakeholder interviews. Qualitative findings indicated overall
      positivity in relation to accessibility, functionality, usefulness, design, and
      increased knowledge of advance care planning. Recommended improvements included
      shortened content, a comparable website for patients and families, and
      multilingual translations. CONCLUSIONS: The CIPP framework was effectively
      applied to evaluate the development and end product of an advance care planning
      website.Although overall findings were positive, further advance care planning
      website development should consider the recommendations derived from this study.

PMID- 29661750
TI  - Relationship Between Weekly Patterns of Caloric Intake and Reported Weight Loss
      Outcomes: Retrospective Cohort Study.
AB  - BACKGROUND: Although millions of overweight and obese adults use mobile phone
      apps for weight loss, little is known about the predictors of success. OBJECTIVE:
      The objective of this study was to understand the relationship between weight
      loss outcomes and weekly patterns of caloric intake among overweight and obese
      adults using a mobile phone app for weight loss. METHODS: We examined the
      relationship between weekly patterns of caloric intake and weight loss outcomes
      among adults who began using a weight loss app in January 2016 and continued
      consistent use for at least 5 months (N=7007). Unadjusted and adjusted linear
      regression analyses were used to evaluate the predictors of percentage of
      bodyweight lost for women and men separately, including age, body mass index
      category, weight loss plan, and difference in daily calories consumed on weekend
      days (Saturday and Sunday) versus Monday. RESULTS: In adjusted linear regression,
      percentage of bodyweight lost was significantly associated with age (for women),
      body mass index (for men), weight loss plan, and differences in daily caloric
      intake on Mondays versus weekend days. Compared with women consuming at least 500
      calories more on weekend days than on Mondays, those who consumed 50 to 250
      calories more on weekend days or those with balanced consumption (+/-50 calories)
      lost 1.64% more and 1.82% more bodyweight, respectively. Women consuming 250 to
      500 calories or more than 500 calories more on Mondays than on weekend days lost
      1.35% more and 3.58% more bodyweight, respectively. Compared with men consuming
      at least 500 calories more on weekend days than on Mondays, those consuming 250
      to 500 calories or more than 500 calories more on Mondays than on weekend days
      lost 2.27% and 3.42% less bodyweight, respectively. CONCLUSIONS: Consistent
      caloric intake on weekend days and Mondays or consuming slightly fewer calories
      per day on Mondays versus weekend days was associated with more successful weight
      loss. TRIAL REGISTRATION: ClinicalTrials.gov NCT03136692;
      https://clinicaltrials.gov/ct2/show/NCT03136692 (Archived by WebCite at
      http://www.webcitation.org/6y9JvHya4).

PMID- 29661751
TI  - Comparison of Online Survey Recruitment Platforms for Hard-to-Reach Pregnant
      Smoking Populations: Feasibility Study.
AB  - BACKGROUND: Recruiting hard-to-reach populations for health research is
      challenging. Web-based platforms offer one way to recruit specific samples for
      research purposes, but little is known about the feasibility of online
      recruitment and the representativeness and comparability of samples recruited
      through different Web-based platforms. OBJECTIVE: The objectives of this study
      were to determine the feasibility of recruiting a hard-to-reach population
      (pregnant smokers) using 4 different Web-based platforms and to compare
      participants recruited through each platform. METHODS: A screener and survey were
      distributed online through Qualtrics Panel, Soapbox Sample, Reddit, and Amazon
      Mechanical Turk (mTurk). Descriptive statistics were used to summarize results of
      each recruitment platform, including eligibility yield, quality yield, income,
      race, age, and gestational age. RESULTS: Of the 3847 participants screened for
      eligibility across all 4 Web-based platforms, 535 were eligible and 308 completed
      the survey. Amazon mTurk yielded the fewest completed responses (n=9), 100% (9/9)
      of which passed several quality metrics verifying pregnancy and smoking status.
      Qualtrics Panel yielded 14 completed responses, 86% (12/14) of which passed the
      quality screening. Soapbox Sample produced 107 completed surveys, 67% (72/107) of
      which were found to be quality responses. Advertising through Reddit produced the
      highest completion rate (n=178), but only 29.2% (52/178) of those surveys passed
      the quality metrics. We found significant differences in eligibility yield,
      quality yield, age, number of previous pregnancies, age of smoking initiation,
      current smokers, race, education, and income (P<.001). CONCLUSIONS: Although each
      platform successfully recruited pregnant smokers, results varied in quality,
      cost, and percentage of complete responses. Moving forward, investigators should
      pay careful attention to the percentage yield and cost of online recruitment
      platforms to maximize internal and external validity.

PMID- 29661753
TI  - Margaret McCartney: Let's start talking to colleagues.

PMID- 29661752
TI  - A Novel Information Retrieval Tool to Find Hospital Care Team Members:
      Development and Usability Study.
AB  - BACKGROUND: Hospital communication among members of a patient's care team is a
      central part of clinical workflow and consumes a large amount of a health care
      provider's time. Oftentimes the complexity of hospital care leads to difficulty
      in finding the appropriate contact, which can lead to inefficiencies and
      frustration. Squire is a Web-based information retrieval app created to improve
      the speed and efficiency in reaching the appropriate team member during the care
      of a hospitalized patient. OBJECTIVE: The objective of the study was to design
      and develop Squire and to evaluate the usage, usability, and perceived effect of
      the app on finding the correct contact within a hospital. METHODS: We used a
      mixed-methods design using a before-after survey methodology combined with one-on
      one interviews to understand the perceived effect of Squire. The study took place
      at an academic medical center with internal medicine resident physicians. We
      surveyed residents on demographics, as well as time and efficiency of hospital
      communication before and after the use of Squire. After using Squire,
      participants were also asked to evaluate Squire's Net Promoter Score (NPS). A
      subset of voluntary participants participated in one-on-one interviews and
      completed the System Usability Scale (SUS). We performed descriptive statistics
      on participant characteristics, app usage data, and responses to surveys. Survey
      results were compared before and after Squire adoption using the Wilcoxon rank
      sum test and a general linear model. Interview data were analyzed using content
      analysis with a qualitative description approach to review and categorize
      feedback from participants. RESULTS: There was a 67.9% (74/109) response rate to
      the pre-Squire survey and 89.9% (98/109) response rate to the post-Squire survey.
      At baseline, there was an average of 22.2 (95% CI 18.4-26.0) minutes/day spent
      searching for the right contact, and this decreased to 16.3 (95% CI 13.9-18.7)
      minutes/day after Squire was launched (P=.01). There were favorable usability
      scores, with an average SUS of 84.7, and a marginal NPS of +6.1. Overall, the use
      of Squire included 22,283 page views, most commonly to contact the admissions
      office or portable chest x-ray technician. Interviews highlighted common benefits
      of Squire, including decreased perceived time spent on hold with operators and
      improvement in connecting with the appropriate contact in specialized, complex
      departments. Future opportunities were also identified to improve Squire
      including adding a two-way communication between physician and nursing staff and
      providing offline access. CONCLUSIONS: Squire decreased the perceived time
      required to find an appropriate contact and had a favorable usability score;
      however, the NPS was marginal and several opportunities were identified to
      improve Squire for future use.

PMID- 29661754
TI  - Approaching the crisis in medical research funding: an important role for
      nonprofit organizations and medical societies.

PMID- 29661756
TI  - Prevention of rickets and osteomalacia in the UK: political action overdue.
AB  - The consequences of vitamin D and dietary calcium deficiency have become a huge
      public health concern in the UK. The burden of disease from these deficiencies
      includes rickets, and hypocalcaemic seizures, dilated cardiomyopathy and mostly
      occult myopathy and osteomalacia. The increasing burden of the disease is
      intrinsically linked to ethnicity and the population demographic changes in the
      UK. Three facts have led to the resurfacing of the English disease: (1) the UK
      has no ultraviolet sunlight for at least 6 months of the year, (2) dark skin
      produces far less vitamin D than white skin per unit ultraviolet light exposure,
      and (3) non-European Union immigration over the last century. To date, the UK
      government demonstrates incomplete understanding of these three facts, and its
      failure to adjust its prevention programmes to changing demographics is
      endangering the health and life of UK residents with dark skin, of whom infants
      are the most vulnerable. Establishing accountability through the implementation
      of monitored antenatal and infantile supplementation programmes and mandatory
      food fortification is overdue.

PMID- 29661755
TI  - A CD123-targeting antibody-drug conjugate, IMGN632, designed to eradicate AML
      while sparing normal bone marrow cells.
AB  - The outlook for patients with refractory/relapsed acute myeloid leukemia (AML)
      remains poor, with conventional chemotherapeutic treatments often associated with
      unacceptable toxicities, including severe infections due to profound
      myelosuppression. Thus there exists an urgent need for more effective agents to
      treat AML that confer high therapeutic indices and favorable tolerability
      profiles. Because of its high expression on leukemic blast and stem cells
      compared with normal hematopoietic stem cells and progenitors, CD123 has emerged
      as a rational candidate for molecularly targeted therapeutic approaches in this
      disease. Here we describe the development and preclinical characterization of a
      CD123-targeting antibody-drug conjugate (ADC), IMGN632, that comprises a novel
      humanized anti-CD123 antibody G4723A linked to a recently reported DNA mono
      alkylating payload of the indolinobenzodiazepine pseudodimer (IGN) class of
      cytotoxic compounds. The activity of IMGN632 was compared with X-ADC, the ADC
      utilizing the G4723A antibody linked to a DNA crosslinking IGN payload. With low
      picomolar potency, both ADCs reduced viability in AML cell lines and patient
      derived samples in culture, irrespective of their multidrug resistance or disease
      status. However, X-ADC exposure was >40-fold more cytotoxic to the normal myeloid
      progenitors than IMGN632. Of particular note, IMGN632 demonstrated potent
      activity in all AML samples at concentrations well below levels that impacted
      normal bone marrow progenitors, suggesting the potential for efficacy in AML
      patients in the absence of or with limited myelosuppression. Furthermore, IMGN632
      demonstrated robust antitumor efficacy in multiple AML xenograft models. Overall,
      these findings identify IMGN632 as a promising candidate for evaluation as a
      novel therapy in AML.

PMID- 29661757
TI  - Hip hip: no hurray.

PMID- 29661758
TI  - High TMB Predicts Immunotherapy Benefit.
AB  - The first data from the phase III CheckMate-227 trial of ipilimumab plus
      nivolumab for the treatment of non-small cell lung cancer suggests that the two
      drugs boost progression-free survival in patients with a high tumor mutation
      burden. After 1 year, progression-free survival was 43% for patients treated with
      the checkpoint inhibitor combination, compared with 13% for patients treated with
      chemotherapy.

PMID- 29661759
TI  - Neoadjuvant Nivolumab Checks Lung Cancer.
AB  - The PD-1 inhibitor nivolumab given prior to surgical removal of early-stage non
      small cell lung cancer is safe and produces a high rate of pathologic response,
      especially among those with high tumor mutation burden.

PMID- 29661760
TI  - April 16th Question.

PMID- 29661761
TI  - Ministers seek to stop GPs charging victims of domestic abuse for information.

PMID- 29661762
TI  - NHS trusts launch legal challenge against councils over business rates.

PMID- 29661763
TI  - Outcomes of Contemporary Family Screening in Hypertrophic Cardiomyopathy.
AB  - BACKGROUND: Contemporary hypertrophic cardiomyopathy (HCM) family screening
      includes clinical evaluation and genetic testing (GT). This screening strategy
      requires the identification of a pathogenic mutation in the proband. Our aim was
      to examine the results of this HCM screening strategy. METHODS: Between 1985 and
      2016, 777 relatives of 209 probands were assessed in the context of HCM
      screening. Genotype-positive (G+) relatives and relatives without genetic testing
      (GT) underwent repeated clinical evaluations. In genotype-negative (G-) relatives
      mortality was assessed during follow-up. RESULTS: A pathogenic mutation was
      identified in 72% of probands. After counseling, GT was performed in 620 (80%)
      relatives: 264 (43%) were G+ (age 41+/-18 y) and 356 (57%) were G- (age 48+/-17
      y). At first screening, HCM was diagnosed in 98 (37%) G+ relatives and 28 (17%)
      relatives without GT (p<0.001). During 9 years follow-up of relatives diagnosed
      with HCM, 8 (6%) underwent septal reduction therapy, 16 (16%) received primary
      prevention ICDs, and cardiac mortality was 0.3%/year. During 7 years follow-up of
      relatives without HCM, 29 (16%) developed HCM. Survival at 5/10 years was 99%/95%
      in G+ relatives, 97%/94% in G- relatives (p=0.8), and 100%/100% in relatives
      without GT. CONCLUSIONS: HCM was identified in 30% of relatives at first
      screening, and 16% developed HCM during 7 years of repeated evaluation. GT led to
      a discharge from clinical follow-up in 46% of the study population. Survival in
      the relatives was good.

PMID- 29661764
TI  - Family Matters: Outcomes of Hypertrophic Cardiomyopathy Family Screening.

PMID- 29661765
TI  - In This Issue: April.

PMID- 29661766
TI  - First concussion did not increase the risk of subsequent concussion when patients
      were managed appropriately.

PMID- 29661767
TI  - 'Pre-activity movement control exercise programme to prevent injuries in youth
      rugby': some concerns.

PMID- 29661768
TI  - The Effect of Learning Styles on Adverse Events in Home Hemodialysis Patients.

PMID- 29661769
TI  - Introduction to Nephropharmacology for the Clinician: A New CJASN Series.

PMID- 29661770
TI  - Hydroxychloroquine Use and Risk of CKD in Patients with Rheumatoid Arthritis.
AB  - BACKGROUND AND OBJECTIVES: Hydroxychloroquine is widely used in patients with
      rheumatoid arthritis. However, large-scale studies examining the long-term
      effects of hydroxychloroquine on the development of kidney disease in patients
      with rheumatoid arthritis are lacking. We aimed to assess the long-term
      association of hydroxychloroquine use with the risk of developing CKD in this
      population. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted an
      observational cohort study for patients with newly diagnosed rheumatoid arthritis
      who were enrolled prospectively in Taiwan's National Health Insurance Research
      Database between January 1, 2000 and December 31, 2013. We used multivariable Cox
      proportional hazard regression to analyze the association of hydroxychloroquine
      use with incident CKD. RESULTS: A total of 2619 patients, including 1212
      hydroxychloroquine users and 1407 hydroxychloroquine nonusers, were analyzed.
      Incident CKD was reported in 48 of 1212 hydroxychloroquine users and 121 of 1407
      hydroxychloroquine nonusers. The incidence rate of CKD was lower in
      hydroxychloroquine users than in hydroxychloroquine nonusers (10.3 versus 13.8
      per 1000 person-years). After multivariable adjustment, hydroxychloroquine users
      still had a lower risk of incident CKD (adjusted hazard ratio, 0.64; 95%
      confidence interval, 0.45 to 0.90; P=0.01) than hydroxychloroquine nonusers. The
      lower risk of subsequent CKD development was dose dependent and consistent across
      subgroup analyses. CONCLUSIONS: Hydroxychloroquine use in patients with newly
      diagnosed rheumatoid arthritis is associated with a significantly lower risk of
      incident CKD compared with in nonusers.

PMID- 29661771
TI  - Antimalarial Drugs for the Prevention of Chronic Kidney Disease in Patients with
      Rheumatoid Arthritis: The Importance of Controlling Chronic Inflammation?

PMID- 29661772
TI  - Communication Strategies to Address Conflict about Dialysis Decision Making for
      Critically Ill Patients.

PMID- 29661773
TI  - Integrated Genomic and Immunophenotypic Classification of Pancreatic Cancer
      Reveals Three Distinct Subtypes with Prognostic/Predictive Significance.
AB  - Purpose: Current clinical classification of pancreatic ductal adenocarcinoma
      (PDAC) is unable to predict prognosis or response to chemo- or immunotherapy and
      does not take into account the host reaction to PDAC cells. Our aim is to
      classify PDAC according to host- and tumor-related factors into
      clinically/biologically relevant subtypes by integrating molecular and
      microenvironmental findings.Experimental Design: A well-characterized PDAC cohort
      (n = 110) underwent next-generation sequencing with a hot spot cancer panel while
      next-generation tissue microarrays were immunostained for CD3, CD4, CD8, CD20, PD
      L1, p63, hyaluronan-mediated motility receptor (RHAMM), and DNA mismatch repair
      proteins. Previous data on FOXP3 were integrated. Immune cell counts and protein
      expression were correlated with tumor-derived driver mutations, clinicopathologic
      features (TNM 8th edition, 2017), survival, and epithelial-mesenchymal transition
      (EMT)-like tumor budding.Results: Three PDAC subtypes were identified: the
      "immune escape" (54%), poor in T and B cells and enriched in FOXP3+ regulatory T
      cells (Treg), with high-grade budding, frequent CDKN2A, SMAD4, and PIK3CA
      mutations, and poor outcome; the "immune rich" (35%), rich in T and B cells and
      poorer in FOXP3+ Tregs, with infrequent budding, lower CDKN2A and PIK3CA mutation
      rate, and better outcome and a subpopulation with tertiary lymphoid tissue (TLT),
      mutations in DNA damage response genes (STK11 and ATM), and the best outcome; and
      the "immune exhausted" (11%), with immunogenic microenvironment and two
      subpopulations-one with PD-L1 expression and a high PIK3CA mutation rate and a
      microsatellite-unstable subpopulation with a high prevalence of JAK3 mutations.
      The combination of low budding, low stromal FOXP3 counts, presence of TLTs, and
      absence of CDKN2A mutations confers significant survival advantage in patients
      with PDAC.Conclusions: Immune host responses correlate with tumor
      characteristics, leading to morphologically recognizable PDAC subtypes with
      prognostic/predictive significance. Clin Cancer Res; 24(18); 4444-54. (c)2018
      AACRSee related commentary by Khalil and O'Reilly, p. 4355.

PMID- 29661774
TI  - Accuracy, Safety, and Reliability of Novel Phase I Trial Designs.
AB  - A number of novel model-based and model-assisted designs have been proposed to
      find the MTD in phase I clinical trials, but their differences and relative pros
      and cons are not clear to many practitioners. We review three model-based
      designs, including the continual reassessment method (CRM), dose escalation with
      overdose control (EWOC), and Bayesian logistic regression model (BLRM), and three
      model-assisted designs, including the modified toxicity probability interval
      (mTPI), Bayesian optimal interval (BOIN), and keyboard (equivalently mTPI-2)
      designs. We conduct numerical studies to assess their accuracy, safety, and
      reliability and the practical implications of various empirical rules used in
      some designs, such as skipping a dose and imposing overdose control. Our results
      show that the CRM outperforms EWOC and BLRM with higher accuracy of identifying
      the MTD. For the CRM, skipping a dose is not recommended, as it substantially
      increases the chance of overdosing patients while providing limited gain for
      identifying the MTD. EWOC and BLRM appear excessively conservative. They are safe
      but have relatively poor accuracy of finding the MTD. The BOIN and keyboard
      (equivalently mTPI-2) designs have similar operating characteristics,
      outperforming the mTPI, but the BOIN is more intuitive and transparent. The BOIN
      yields competitive performance comparable with the CRM but is simpler to
      implement and free of the issue of irrational dose assignment caused by model
      misspecification, thereby providing an attractive approach for designing phase I
      trials. Clin Cancer Res; 24(18); 4357-64. (c)2018 AACR.

PMID- 29661775
TI  - Prospective Clinical Trial of Ixazomib, Dexamethasone, and Rituximab as Primary
      Therapy in Waldenstrom Macroglobulinemia.
AB  - Purpose: Proteasome inhibition is of proven efficacy in patients with Waldenstrom
      macroglobulinemia (WM). However, WM remains incurable with standard treatments.
      Novel agents, safe and effective, are needed.Patients and Methods: We designed a
      prospective phase II study evaluating the combination of ixazomib, dexamethasone,
      and rituximab (IDR) as primary therapy in symptomatic patients with WM. Protocol
      therapy consisted of oral ixazomib, 4 mg, with intravenous or oral dexamethasone,
      20 mg, on days 1, 8, and 15 every 4 weeks for induction cycles 1 and 2, and in
      combination with intravenous rituximab, 375 mg/m2, on day 1, every 4 weeks for
      cycles 3 to 6. Maintenance therapy followed 8 weeks later with IDR given every 8
      weeks for 6 cycles.Results: Twenty-six patients were enrolled. All patients had
      the MYD88 L265P mutation, and 15 patients (58%) had a CXCR4 mutation. The median
      time to response was 8 weeks, which was longer (12 weeks) in WM patients with
      CXCR4 mutations (P = 0.03). The overall response rate was 96%, and the major
      response rate was 77%. With a median follow-up of 22 months, the median
      progression-free survival was not reached. Grade >=2 adverse events reported in
      >1 patient included infusion-related reactions (19%), rash (8%), and insomnia
      (8%).Conclusions: IDR offers a highly effective and well tolerated, neuropathy
      sparing regimen for primary therapy in patients with WM. This trial is registered
      at www.clinicaltrials.gov under ID NCT02400437 Clin Cancer Res; 24(14); 3247-52.
      (c)2018 AACR.

PMID- 29661776
TI  - Targeting the Leukemia Antigen PR1 with Immunotherapy for the Treatment of
      Multiple Myeloma.
AB  - Purpose: PR1 is a human leukocyte antigen (HLA)-A2 nonameric peptide derived from
      neutrophil elastase (NE) and proteinase 3 (P3). We have previously shown that PR1
      is cross-presented by solid tumors, leukemia, and antigen-presenting cells,
      including B cells. We have also shown that cross-presentation of PR1 by solid
      tumors renders them susceptible to killing by PR1-targeting immunotherapies. As
      multiple myeloma is derived from B cells, we investigated whether multiple
      myeloma is also capable of PR1 cross-presentation and subsequently capable of
      being targeted by using PR1 immunotherapies.Experimental Design: We tested
      whether multiple myeloma is capable of cross-presenting PR1 and subsequently
      becomes susceptible to PR1-targeting immunotherapies, using multiple myeloma cell
      lines, a xenograft mouse model, and primary multiple myeloma patient
      samples.Results: Here we show that multiple myeloma cells lack endogenous NE and
      P3, are able to take up exogenous NE and P3, and cross-present PR1 on HLA-A2.
      Cross-presentation by multiple myeloma utilizes the conventional antigen
      processing machinery, including the proteasome and Golgi, and is not affected by
      immunomodulating drugs (IMiD). Following PR1 cross-presentation, we are able to
      target multiple myeloma with PR1-CTL and anti-PR1/HLA-A2 antibody both in vitro
      and in vivoConclusions: Collectively, our data demonstrate that PR1 is a novel
      tumor-associated antigen target in multiple myeloma and that multiple myeloma is
      susceptible to immunotherapies that target cross-presented antigens. Clin Cancer
      Res; 24(14); 3386-96. (c)2018 AACR.

PMID- 29661777
TI  - Interferon-Stimulated Genes Are Involved in Cross-resistance to Radiotherapy in
      Tamoxifen-Resistant Breast Cancer.
AB  - Purpose: Treatment resistance is the main cause of adverse disease outcome in
      breast cancer patients. Here, we aimed to investigate common features in
      tamoxifen-resistant and radioresistant breast cancer, as tamoxifen-resistant
      breast cancer cells are cross-resistant to irradiation in vitroExperimental
      Design: RNA sequencing of tamoxifen-resistant and radioresistant breast cancer
      cells was performed and validated by quantitative PCR. Pathways were further
      investigated in vitro and in breast cancer patient cohorts to establish their
      relation with treatment resistance.Results: Both tamoxifen-resistant and
      radioresistant breast cancer cells had increased expression levels of genes
      involved in type I IFN signaling compared with nonresistant cells. IFN-stimulated
      genes (ISG) were induced in a dose-dependent and time-dependent manner after
      tamoxifen treatment and irradiation. Tamoxifen treatment also led to ssDNA
      presence in the cytoplasm, which is known to induce expression of ISGs, a
      phenomenon that has already been described for irradiation. Moreover, in a breast
      cancer patient cohort, high expression levels of ISGs were found in the primary
      tumor in around half of the patients. This was associated with a tumor
      infiltrating lymphocyte (TIL) expression signature, although the ISGs were also
      expressed by the tumor cells themselves. Importantly, the expression of ISGs
      correlated with outcome in breast cancer patients treated with adjuvant tamoxifen
      or radiotherapy, but not in systemically untreated patients or chemotherapy
      treated patients.Conclusions: Our data indicate that expression of ISGs by tumor
      cells is involved in acquired, treatment-induced resistance to tamoxifen and
      radiotherapy, and might play a role in intrinsic resistance via interaction with
      TILs. Clin Cancer Res; 24(14); 3397-408. (c)2018 AACR.

PMID- 29661778
TI  - Immunogenomic Analyses of Advanced Serous Ovarian Cancer Reveal Immune Score is a
      Strong Prognostic Factor and an Indicator of Chemosensitivity.
AB  - Purpose: Ovarian cancer is one of the first human cancers for which in situ
      immune response was reported to be important for the clinical outcome. To
      elucidate the mechanistic relationship between immune repertoire and cancer
      genotype in ovarian cancer, the development of a well-defined immune score for
      ovarian cancer is required.Experimental Design: From a collection of 2,203
      patient samples of advanced ovarian cancer from public available resources, we
      evaluated the prognostic values for a compendium of immune marker genes and
      proposed an immune score. The relationships between immune score, tumor
      infiltrating immune cells, cancer genotypes, and their impact on patient outcome
      were characterized.Results: Loss of chemokine and IFNgamma pathway genes is
      frequent in ovarian cancer and is significantly associated with low immune score
      and poor outcome. Chemotherapy can increase the immune score of tumors by
      inducing the expression of IFNgamma inducible chemokines. High immune score is
      significantly associated with BRCA1/2 mutation status and the response to
      chemotherapy. Multivariate analysis revealed that immune score is a strong
      predictor of patient survival and the response to immunotherapy.Conclusions: Our
      results reveal the drivers of the immune repertoire of advanced ovarian cancer
      and demonstrate the importance of immune score as an independent prognostic
      signature and a potent indicator of intratumoral immune status. Clin Cancer Res;
      24(15); 3560-71. (c)2018 AACR.

PMID- 29661779
TI  - Report from the SWOG Radiation Oncology Committee: Research Objectives Workshop
      2017.
AB  - The Radiation Therapy Committee of SWOG periodically evaluates its strategic plan
      in an effort to maintain a current and relevant scientific focus, and to provide
      a standard platform for future development of protocol concepts. Participants in
      the 2017 Strategic Planning Workshop included leaders in cancer basic sciences,
      molecular theragnostics, pharmaceutical and technology industries, clinical trial
      design, oncology practice, and statistical analysis. The committee discussed high
      priority research areas, such as optimization of combined modality therapy,
      radiation oncology-specific drug design, identification of molecular profiles
      predictive of radiation-induced local or distant tumor responses, and methods for
      normal tissue-specific mitigation of radiation toxicity. The following concepts
      emerged as dominant questions ready for national testing: (i) what is the role of
      radiotherapy in the treatment of oligometastatic, oligorecurrent, and
      oligoprogressive disease? (ii) How can combined modality therapy be used to
      enhance systemic and local response? (iii) Can we validate and optimize liquid
      biopsy and other biomarkers (such as novel imaging) to supplement current
      response criteria to guide therapy and clinical trial design endpoints? (iv) How
      can we overcome deficiencies of randomized survival endpoint trials in an era of
      increasing molecular stratification factors? And (v) how can we mitigate
      treatment-related side effects and maximize quality of life in cancer survivors?
      The committee concluded that many aspects of these questions are ready for
      clinical evaluation and example protocol concepts are provided that could improve
      rates of cancer cure and quality of survival. Clin Cancer Res; 24(15); 3500-9.
      (c)2018 AACR.

PMID- 29661780
TI  - Gender and survival from out-of-hospital cardiac arrest: a New Zealand registry
      study.
AB  - OBJECTIVE: To determine the relationships between survival from all-cause out-of
      hospital cardiac arrest (OHCA) and gender in New Zealand. METHODS: A
      retrospective observational study was conducted using data compliant with the
      Utstein guidelines from the St John New Zealand OHCA Registry for adult patients
      who were treated for an OHCA between 1 October 2013 and 30 September 2015.
      Univariate logistic regression was used to investigate factors associated with
      return of spontaneous circulation sustained to handover at hospital and survival
      to 30 days. Multivariate logistic regression models were used to investigate
      outcome differences in survival according to gender at 30 days postevent.
      RESULTS: Women survived to hospital handover in 29% of cases, which was not
      significantly different from men (31%). When adjusted for age, location,
      aetiology, initial rhythm and witnessed status, there was no significant
      difference in 30-day survival between men (16%) and women (13%) (adjusted OR
      1.22, 95% CI (0.96 to 1.55), p=0.11). CONCLUSION: No statistical differences were
      found in 30-day survival between genders when adjustments for unfavourable
      Utstein variables were accounted for.

PMID- 29661781
TI  - Relation of Aortic Stiffness to Left Ventricular Remodeling in Younger Adults
      With Type 2 Diabetes.
AB  - Individuals with type 2 diabetes have a three- to fivefold increased risk of
      developing heart failure. Diabetic cardiomyopathy is typified by left ventricular
      (LV) concentric remodeling, which is a recognized predictor of adverse
      cardiovascular events. Although the mechanisms underlying LV remodeling in type 2
      diabetes are unclear, progressive aortic stiffening may be a key determinant. The
      aim of this study was to assess the relationship between aortic stiffness and LV
      geometry in younger adults with type 2 diabetes, using multiparametric
      cardiovascular MRI. We prospectively recruited 80 adults (aged 18-65 years) with
      type 2 diabetes and no cardiovascular disease and 20 age- and sex-matched healthy
      control subjects. All subjects underwent comprehensive bio-anthropometric
      assessment and cardiac MRI, including measurement of aortic stiffness by aortic
      distensibility (AD). Type 2 diabetes was associated with increased LV mass,
      concentric LV remodeling, and lower AD compared with control subjects. On
      multivariable linear regression, AD was independently associated with concentric
      LV remodeling in type 2 diabetes. Aortic stiffness may therefore be a potential
      therapeutic target to prevent the development of heart failure in type 2
      diabetes.

PMID- 29661782
TI  - Doc2b Protects beta-Cells Against Inflammatory Damage and Enhances Function.
AB  - Loss of functional beta-cell mass is an early feature of type 1 diabetes. To
      release insulin, beta-cells require soluble N-ethylmaleimide-sensitive factor
      attachment protein receptor (SNARE) complexes, as well as SNARE complex
      regulatory proteins like double C2 domain-containing protein beta (Doc2b). We
      hypothesized that Doc2b deficiency or overabundance may confer susceptibility or
      protection, respectively, to the functional beta-cell mass. Indeed, Doc2b+/-
      knockout mice show an unusually severe response to multiple-low-dose
      streptozotocin (MLD-STZ), resulting in more apoptotic beta-cells and a smaller
      beta-cell mass. In addition, inducible beta-cell-specific Doc2b-overexpressing
      transgenic (betaDoc2b-dTg) mice show improved glucose tolerance and resist MLD
      STZ-induced disruption of glucose tolerance, fasting hyperglycemia, beta-cell
      apoptosis, and loss of beta-cell mass. Mechanistically, Doc2b enrichment enhances
      glucose-stimulated insulin secretion (GSIS) and SNARE activation and prevents the
      appearance of apoptotic markers in response to cytokine stress and thapsigargin.
      Furthermore, expression of a peptide containing the Doc2b tandem C2A and C2B
      domains is sufficient to confer the beneficial effects of Doc2b enrichment on
      GSIS, SNARE activation, and apoptosis. These studies demonstrate that Doc2b
      enrichment in the beta-cell protects against diabetogenic and proapoptotic
      stress. Furthermore, they identify a Doc2b peptide that confers the beneficial
      effects of Doc2b and may be a therapeutic candidate for protecting functional
      beta-cell mass.

PMID- 29661784
TI  - MECHANISMS IN ENDOCRINOLOGY: A sense of time of the glucocorticoid circadian
      clock: from the ontogeny to the diagnosis of Cushing's syndrome.
AB  - The circadian rhythm of glucocorticoids has long been recognised within the last
      75 years. Since the beginning, researchers have sought to identify basic
      mechanisms underlying the origin and emergence of the corticosteroid circadian
      rhythmicity among mammals. Accordingly, Young, Hall and Rosbash, laureates of the
      2017 Nobel Prize in Physiology or Medicine, as well as Takahashi's group among
      others, have characterised the molecular cogwheels of the circadian system,
      describing interlocking transcription/translation feedback loops essential for
      normal circadian rhythms. Plasma glucocorticoid circadian variation depends on
      the expression of intrinsic clock genes within the anatomic components of the
      hypothalamic-pituitary-adrenal axis, which are organised in a hierarchical
      manner. This review presents a general overview of the glucocorticoid circadian
      clock mechanisms, highlighting the ontogeny of the pituitary-adrenal axis diurnal
      rhythmicity as well as the involvement of circadian rhythm abnormalities in the
      physiopathology and diagnosis of Cushing's disease.

PMID- 29661783
TI  - Conserved and divergent functions of Pax6 underlie species-specific neurogenic
      patterns in the developing amniote brain.
AB  - The evolution of unique organ structures is associated with changes in conserved
      developmental programs. However, characterizing the functional conservation and
      variation of homologous transcription factors (TFs) that dictate species-specific
      cellular dynamics has remained elusive. Here, we dissect shared and divergent
      functions of Pax6 during amniote brain development. Comparative functional
      analyses revealed that the neurogenic function of Pax6 is highly conserved in the
      developing mouse and chick pallium, whereas stage-specific binary functions of
      Pax6 in neurogenesis are unique to mouse neuronal progenitors, consistent with
      Pax6-dependent temporal regulation of Notch signaling. Furthermore, we identified
      that Pax6-dependent enhancer activity of Dbx1 is extensively conserved between
      mammals and chick, although Dbx1 expression in the developing pallium is highly
      divergent in these species. Our results suggest that spatiotemporal changes in
      Pax6-dependent regulatory programs contributed to species-specific neurogenic
      patterns in mammalian and avian lineages, which underlie the morphological
      divergence of the amniote pallial architectures.

PMID- 29661785
TI  - The prevalence of the metabolic syndrome and associated cardiovascular
      complications in adult-onset GHD during GH replacement: a KIMS analysis.
AB  - BACKGROUND: Adult-onset growth hormone deficiency (AO-GHD) is associated with an
      increased prevalence of the metabolic syndrome (MetS). AIM: To determine the
      effect of GH replacement on the prevalence of MetS in AO-GHD and to study the
      impact of MetS on the incidence of cardiovascular events during GH replacement.
      PATIENTS AND METHODS: 1449 AO-GHD patients (males 48.9%; mean age 48.9 +/- 12.8
      year) were retrieved from KIMS (Pfizer International Metabolic Database). The
      prevalence of MetS (using International Diabetes Federation criteria) and its
      components were calculated at baseline and after one year of GH replacement. The
      relative risk to develop cardiovascular events according to the presence of MetS
      at baseline was assessed in another group of 3282 patients after prolonged GH
      replacement. RESULTS: The prevalence of MetS was 46.9% at baseline and 48.2%
      after one year of GH replacement (P = NS). The percentage of patients with
      abnormal waist circumference decreased significantly (80.3 vs 77.4%; P < 0.001),
      but impaired glucose metabolism (17.1 vs 23.3%; P < 0.001) increased and HDL
      cholesterol (48.2 vs 50.9%; P = 0.011) decreased. Switch from MetS to NoMS
      (18.5%) and from NoMS to MetS (18.8%) occurred. All patients showed a significant
      and comparable amelioration of quality of life. During seven years of GH
      replacement patients with MetS had a 66% higher risk (P = 0.0016) to develop a
      new coronary disease compared to NoMS. CONCLUSION: MetS prevalence remains
      unchanged in AO-GHD during one year of GH replacement whereas its components are
      differentially affected. Besides GH replacement, consequent pharmacotherapy of
      all risk factors and endorsement of lifestyle intervention appears to be of
      uttermost importance together with early GHD diagnosis to prevent cardiovascular
      disease during prolonged treatment.

PMID- 29661787
TI  - Thromboembolism in acute lymphoblastic leukemia: results of NOPHO ALL2008
      protocol treatment in patients aged 1 to 45 years.
AB  - Thromboembolism frequently occurs during acute lymphoblastic leukemia (ALL)
      therapy. We prospectively registered thromboembolic events during the treatment
      of 1772 consecutive Nordic/Baltic patients with ALL aged 1 to 45 years who were
      treated according to the Nordic Society of Pediatric Hematology and Oncology
      ALL2008 protocol (July 2008-April 2017). The 2.5-year cumulative incidence of
      thromboembolism (N = 137) was 7.9% (95% confidence interval [CI], 6.6-9.1); it
      was higher in patients aged at least 10 years (P < .0001). Adjusted hazard ratios
      (HRas) were associated with greater age (range, 10.0-17.9 years: HRa, 4.9 [95%
      CI, 3.1-7.8; P < .0001]; 18.0-45.9 years: HRa, 6.06 [95% CI, 3.65-10.1; P <
      .0001]) and mediastinal mass at ALL diagnosis (HRa, 2.1; 95% CI, 1.0-4.3; P =
      .04). In a multiple absolute risk regression model addressing 3 thromboembolism
      risk factors, age at least 10 years had the largest absolute risk ratio (RRage,
      4.7 [95% CI, 3.1-7.1]; RRenlarged lymph nodes, 2.0 [95% CI, 1.2-3.1];
      RRmediastinal mass, 1.6 [95% CI, 1.0-2.6]). Patients aged 18.0 to 45.9 years had
      an increased hazard of pulmonary embolism (HRa, 11.6; 95% CI, 4.02-33.7; P <
      .0001), and patients aged 10.0 to 17.9 years had an increased hazard of cerebral
      sinus venous thrombosis (HRa, 3.3; 95% CI, 1.5-7.3; P = .003) compared with
      children younger than 10.0 years. Asparaginase was truncated in 38/128 patients
      with thromboembolism, whereas thromboembolism diagnosis was unassociated with
      increased hazard of relapse (P = .6). Five deaths were attributable to
      thromboembolism, and patients younger than 18.0 years with thromboembolism had
      increased hazard of dying compared with same-aged patients without
      thromboembolism (both P <= .01). In conclusion, patients aged at least 10 years
      could be candidates for preemptive antithrombotic prophylaxis. However, the
      predictive value of age 10 years or older, enlarged lymph nodes, and mediastinal
      mass remain to be validated in another cohort.

PMID- 29661788
TI  - Germ line tissues for optimal detection of somatic variants in myelodysplastic
      syndromes.

PMID- 29661789
TI  - Late mortality after autologous blood or marrow transplantation in childhood: a
      Blood or Marrow Transplant Survivor Study-2 report.
AB  - Autologous blood or marrow transplantation (BMT) is a curative option for several
      types of childhood cancer. However, there is little information regarding the
      risk of late mortality. We examined all-cause mortality, relapse-related
      mortality (RRM), and nonrelapse-related mortality (NRM) in 2-year survivors of
      autologous BMT performed before age 22 between 1980 and 2010 at 1 of 2 US
      transplant centers. Vital status information was collected using medical records,
      National Death Index, and Accurint databases. Overall survival was calculated
      using Kaplan-Meier techniques. Cumulative incidence of mortality used competing
      risk methods. Standardized mortality ratio (SMR) was calculated using age-, sex-,
      and calendar-specific mortality rates from Centers for Disease Control and
      Prevention. Cox regression analysis was used to determine predictors of all-cause
      late mortality. Among the 345 2-year survivors, 103 deaths were observed,
      yielding an overall survival of 70.3% 15 years post-BMT. The leading causes of
      death included primary disease (50.0%), subsequent neoplasm (21.4%), and
      infection (18.2%). Overall, the cohort was at a 22-fold increased risk of late
      mortality (SMR, 21.8; 95% CI, 17.9-26.3), compared with the general population.
      Mortality rates remained elevated among the 10-year survivors (SMR, 20.6; 95% CI,
      9.9-37.2) but approached those of the general population >=15 years post-BMT. The
      10-year cumulative incidence of RRM (14.3%) exceeded that of NRM (10.4%). The 10
      year cumulative mortality rate declined over time (<1990, 35.1%; 1990-1999,
      25.6%; 2000-2010, 21.8%; P = .05). In conclusion, childhood autologous BMT
      recipients have an increased risk of late mortality, compared with the general
      population. The late mortality rates have declined over the past 3 decades.

PMID- 29661786
TI  - Historical perspective: phosphatidylserine and phosphatidylethanolamine from the
      1800s to the present.
AB  - This article provides a historical account of the discovery, chemistry, and
      biochemistry of two ubiquitous phosphoglycerolipids, phosphatidylserine (PS) and
      phosphatidylethanolamine (PE), including the ether lipids. In addition, the
      article describes the biosynthetic pathways for these phospholipids and how these
      pathways were elucidated. Several unique functions of PS and PE in mammalian
      cells in addition to their ability to define physical properties of membranes are
      discussed. For example, the translocation of PS from the inner to the outer
      leaflet of the plasma membrane of cells occurs during apoptosis and during some
      other specific physiological processes, and this translocation is responsible for
      profound life-or-death events. Moreover, mitochondrial function is severely
      impaired when the PE content of mitochondria is reduced below a threshold level.
      The discovery and implications of the existence of membrane contact sites between
      the endoplasmic reticulum and mitochondria and their relevance for PS and PE
      metabolism, as well as for mitochondrial function, are also discussed. Many of
      the recent advances in these fields are due to the use of isotope labeling for
      tracing biochemical pathways. In addition, techniques for disruption of specific
      genes in mice are now widely used and have provided major breakthroughs in
      understanding the roles and metabolism of PS and PE in vivo.

PMID- 29661790
TI  - Translation in Prokaryotes.
AB  - This review summarizes our current understanding of translation in prokaryotes,
      focusing on the mechanistic and structural aspects of each phase of translation:
      initiation, elongation, termination, and ribosome recycling. The assembly of the
      initiation complex provides multiple checkpoints for messenger RNA (mRNA) and
      start-site selection. Correct codon-anticodon interaction during the decoding
      phase of elongation results in major conformational changes of the small
      ribosomal subunit and shapes the reaction pathway of guanosine triphosphate (GTP)
      hydrolysis. The ribosome orchestrates proton transfer during peptide bond
      formation, but requires the help of elongation factor P (EF-P) when two or more
      consecutive Pro residues are to be incorporated. Understanding the choreography
      of transfer RNA (tRNA) and mRNA movements during translocation helps to place the
      available structures of translocation intermediates onto the time axis of the
      reaction pathway. The nascent protein begins to fold cotranslationally, in the
      constrained space of the polypeptide exit tunnel of the ribosome. When a stop
      codon is reached at the end of the coding sequence, the ribosome, assisted by
      termination factors, hydrolyzes the ester bond of the peptidyl-tRNA, thereby
      releasing the nascent protein. Following termination, the ribosome is dissociated
      into subunits and recycled into another round of initiation. At each step of
      translation, the ribosome undergoes dynamic fluctuations between different
      conformation states. The aim of this article is to show the link between ribosome
      structure, dynamics, and function.

PMID- 29661791
TI  - Interferon gamma and Its Important Roles in Promoting and Inhibiting Spontaneous
      and Therapeutic Cancer Immunity.
AB  - Originally identified in studies of cellular resistance to viral infection,
      interferon (IFN)-gamma is now known to represent a distinct member of the IFN
      family and plays critical roles not only in orchestrating both innate and
      adaptive immune responses against viruses, bacteria, and tumors, but also in
      promoting pathologic inflammatory processes. IFN-gamma production is largely
      restricted to T lymphocytes and natural killer (NK) cells and can ultimately lead
      to the generation of a polarized immune response composed of T helper (Th)1 CD4+
      T cells and CD8+ cytolytic T cells. In contrast, the temporally distinct
      elaboration of IFN-gamma in progressively growing tumors also promotes a state of
      adaptive resistance caused by the up-regulation of inhibitory molecules, such as
      programmed-death ligand 1 (PD-L1) on tumor cell targets, and additional host
      cells within the tumor microenvironment. This review focuses on the diverse
      positive and negative roles of IFN-gamma in immune cell activation and
      differentiation leading to protective immune responses, as well as the
      paradoxical effects of IFN-gamma within the tumor microenvironment that determine
      the ultimate fate of that tumor in a cancer-bearing individual.

PMID- 29661793
TI  - Cell-Free Plasma DNA for Disease Stratification and Prognosis in Head and Neck
      Cancer.
AB  - BACKGROUND: Clinicians face many challenges in disease stratification and outcome
      prediction in head and neck squamous cancer cell (HNSCC) patients. Given the
      limitations of currently used clinical scoring, repetitive biopsies, and imaging
      techniques, liquid biopsy approaches may provide valuable additional diagnostic
      and prognostic information. METHODS: A noninterventional, single-center
      observational study was performed with clinical data and plasma samples from
      HNSCC patients. Cell-free tumor DNA-derived copy number aberrations (CNAs) were
      determined in 116 patients by low-coverage next-generation sequencing (NGS).
      Significant CNAs were combined in a genome-wide copy number instability score
      (CNI), which was evaluated with respect to conventional clinical staging and
      patient outcome. RESULTS: Receiver-operating characteristic (ROC) curve analysis
      comparing the presurgery CNI in patients (n = 103) with that in tumor-free
      controls (n = 142) yielded an area under the ROC curve of 87.2% (95% CI, 79.4%
      93.3%). At a specificity of 95%, the sensitivity to detect tumors varied between
      46% (pT1) and 94% (pT4). A CNI above the median (i.e., >72) had a positive
      predictive value of 90% (95% CI, 79%-96%) for lymph node involvement (LNI), while
      the negative predictive value was 57% (95% CI, 43%-70%). For a CNI >72, overall
      survival (OS) was worse (hazard ratio, 4.89; 95% CI, 1.39-17.17; P = 0.01) with
      62% and 90% survivors 3 years after surgery for a CNI >72 and <=72, respectively.
      In multivariable models, the CNI was a superior predictor of OS compared to
      established disease features, including LNI. CONCLUSIONS: The CNI may assist in
      predicting LNI and prognosis in HNSCC with direct therapeutic implications
      concerning the need for neck dissection or more aggressive treatment.

PMID- 29661792
TI  - Using single-cell genomics to understand developmental processes and cell fate
      decisions.
AB  - High-throughput -omics techniques have revolutionised biology, allowing for
      thorough and unbiased characterisation of the molecular states of biological
      systems. However, cellular decision-making is inherently a unicellular process to
      which "bulk" -omics techniques are poorly suited, as they capture ensemble
      averages of cell states. Recently developed single-cell methods bridge this gap,
      allowing high-throughput molecular surveys of individual cells. In this review,
      we cover core concepts of analysis of single-cell gene expression data and
      highlight areas of developmental biology where single-cell techniques have made
      important contributions. These include understanding of cell-to-cell
      heterogeneity, the tracing of differentiation pathways, quantification of gene
      expression from specific alleles, and the future directions of cell lineage
      tracing and spatial gene expression analysis.

PMID- 29661794
TI  - Reciprocal regulation of TEAD4 and CCN2 for the trophectoderm development of the
      bovine blastocyst.
AB  - The first segregation at the blastocyst stage is the symmetry-breaking event to
      characterize two cell components; namely, inner cell mass (ICM) and trophectoderm
      (TE). TEA domain transcription factor 4 (TEAD4) is a well-known regulator to
      determine TE properties of blastomeres in rodent models. However, the roles of
      bovine TEAD4 in blastocyst development have been unclear. We here aimed to
      clarify the mechanisms underlining TE characterization by TEAD4 in bovine
      blastocysts. We first found that the TEAD4 mRNA expression level was greater in
      TE than in ICM, which was further supported by TEAD4 immunofluorescent staining.
      Subsequently, we examined the expression patterns of TE-expressed genes; CDX2,
      GATA2 and CCN2, in the TEAD4-knockdown (KD) blastocysts. These expression levels
      significantly decreased in the TEAD4 KD blastocysts compared with controls. Of
      these downregulated genes, the CCN2 expression level decreased the most. We
      further analyzed the expression levels of TE-expressed genes; CDX2, GATA2 and
      TEAD4 in the CCN2 KD blastocysts. Strikingly, the CCN2 KD blastocysts showed the
      downregulation of CDX2, GATA2 and TEAD4 Furthermore, the ratio of TE-to-ICM cell
      numbers in the CCN2 KD blastocysts significantly decreased compared to controls.
      To our knowledge, this is the first study showing the regulation of CCN2
      expression thorough TEAD4 in mammalian embryos. Not only that, this study also
      provides evidence that reciprocal regulation of TEAD4 and CCN2 is required for TE
      development with appropriate gene expression in bovine blastocysts.

PMID- 29661795
TI  - Machine Learning Analysis of Left Ventricular Function to Characterize Heart
      Failure With Preserved Ejection Fraction.
AB  - BACKGROUND: Current diagnosis of heart failure with preserved ejection fraction
      (HFpEF) is suboptimal. We tested the hypothesis that comprehensive machine
      learning (ML) of left ventricular function at rest and exercise objectively
      captures differences between HFpEF and healthy subjects. METHODS AND RESULTS: One
      hundred fifty-six subjects aged >60 years (72 HFpEF+33 healthy for the initial
      analyses; 24 hypertensive+27 breathless for independent evaluation) underwent
      stress echocardiography, in the MEDIA study (Metabolic Road to Diastolic Heart
      Failure). Left ventricular long-axis myocardial velocity patterns were analyzed
      using an unsupervised ML algorithm that orders subjects according to their
      similarity, allowing exploration of the main trends in velocity patterns. ML
      identified a continuum from health to disease, including a transition zone
      associated to an uncertain diagnosis. Clinical validation was performed (1) to
      characterize the main trends in the patterns for each zone, which corresponded to
      known characteristics and new features of HFpEF; the ML-diagnostic zones differed
      for age, body mass index, 6-minute walk distance, B-type natriuretic peptide, and
      left ventricular mass index (P<0.05) and (2) to evaluate the consistency of the
      proposed groupings against diagnosis by current clinical criteria; correlation
      with diagnosis was good (kappa, 72.6%; 95% confidence interval, 58.1-87.0); ML
      identified 6% of healthy controls as HFpEF. Blinded reinterpretation of imaging
      from subjects with discordant clinical and ML diagnoses revealed abnormalities
      not included in diagnostic criteria. The algorithm was applied independently to
      another 51 subjects, classifying 33% of hypertensive and 67% of breathless
      controls as mild-HFpEF. CONCLUSIONS: The analysis of left ventricular long-axis
      function on exercise by interpretable ML may improve the diagnosis and
      understanding of HFpEF.

PMID- 29661796
TI  - Imaging Heart Failure With Artificial Intelligence: Improving the Realism of
      Synthetic Wisdom.

PMID- 29661797
TI  - Fank1 and Jazf1 promote multiciliated cell differentiation in the mouse airway
      epithelium.
AB  - The airways are lined by secretory and multiciliated cells which function
      together to remove particles and debris from the respiratory tract. The
      transcriptome of multiciliated cells has been extensively studied, but the
      function of many of the genes identified is unknown. We have established an assay
      to test the ability of over-expressed transcripts to promote multiciliated cell
      differentiation in mouse embryonic tracheal explants. Overexpression data
      indicated that Fibronectin type 3 and ankyrin repeat domains 1 (Fank1) and JAZF
      zinc finger 1 (Jazf1) promoted multiciliated cell differentiation alone, and
      cooperatively with the canonical multiciliated cell transcription factor Foxj1.
      Moreover, knock-down of Fank1 or Jazf1 in adult mouse airway epithelial cultures
      demonstrated that these factors are both required for ciliated cell
      differentiation in vitro This analysis identifies Fank1 and Jazf1 as novel
      regulators of multiciliated cell differentiation. Moreover, we show that they are
      likely to function downstream of IL6 signalling and upstream of Foxj1 activity in
      the process of ciliated cell differentiation. In addition, our in vitro explant
      assay provides a convenient method for preliminary investigation of over
      expression phenotypes in the developing mouse airways.This article has an
      associated First Person interview with the first author of the paper.

PMID- 29661800
TI  - Chorionic somatomammotropin impacts early fetal growth and placental gene
      expression.
AB  - Several developmental windows, including placentation, must be negotiated to
      establish and maintain pregnancy. Impaired placental function can lead to
      preeclampsia and/or intrauterine growth restriction (IUGR), resulting in
      increased infant mortality and morbidity. It has been hypothesized that chorionic
      somatomammotropin (CSH) plays a significant role in fetal development,
      potentially by modifying maternal and fetal metabolism. Recently, using
      lentiviral-mediated in vivo RNA interference in sheep, we demonstrated
      significant reductions in near-term (135 days of gestation; dGA) fetal and
      placental size, and altered fetal liver gene expression, resulting from CSH
      deficiency. We sought to examine the impact of CSH deficiency on fetal and
      placental size earlier in gestation (50 dGA), and to examine placental gene
      expression at 50 and 135 dGA. At 50 dGA, CSH-deficient pregnancies exhibited a
      41% reduction (P <= 0.05) in uterine vein concentrations of CSH, and significant
      (P <= 0.05) reductions (~21%) in both fetal body and liver weights. Placentae
      harvested at 50 and 135 dGA exhibited reductions in IGF1 and IGF2 mRNA
      concentrations, along with reductions in SLC2A1 and SLC2A3 mRNA. By contrast,
      mRNA concentrations for various members of the System A, System L and System y+
      amino acid transporter families were not significantly impacted. The IUGR
      observed at the end of the first-third of gestation indicates that the near-term
      IUGR reported previously, began early in gestation, and may have in part resulted
      from deficits in the paracrine action of CSH within the placenta. These results
      provide further compelling evidence for the importance of CSH in the progression
      and outcome of pregnancy.

PMID- 29661799
TI  - The role of beta cell heterogeneity in islet function and insulin release.
AB  - It is becoming increasingly apparent that not all insulin-secreting beta cells
      are equal. Subtle differences exist at the transcriptomic and protein expression
      levels, with repercussions for beta cell survival/proliferation, calcium
      signalling and insulin release. Notably, beta cell heterogeneity displays
      plasticity during development, metabolic stress and type 2 diabetes mellitus
      (T2DM). Thus, heterogeneity or lack thereof may be an important contributor to
      beta cell failure during T2DM in both rodents and humans. The present review will
      discuss the molecular and cellular features of beta cell heterogeneity at both
      the single-cell and islet level, explore how this influences islet function and
      insulin release and look into the alterations that may occur during obesity and
      T2DM.

PMID- 29661801
TI  - Anti-CA15.3 and Anti-CA125 Antibodies and Ovarian Cancer Risk: Results from the
      EPIC Cohort.
AB  - Background: Neoplastic and non-neoplastic events may raise levels of mucins,
      CA15.3, and CA125, and generate antibodies against them, but their impact on
      epithelial ovarian cancer (EOC) risk has not been fully defined.Methods: CA15.3,
      CA125, and IgG1 antibodies against them were measured in 806 women who developed
      EOC and 1,927 matched controls from the European Prospective Investigation of
      Nutrition and Cancer. Associations between epidemiologic factors and anti-mucin
      antibodies were evaluated using generalized linear models; EOC risks associated
      with anti-mucin antibodies, by themselves or in combination with respective
      antigens, were evaluated using conditional logistic regression.Results: In
      controls, lower antibodies against both mucins were associated with current
      smoking; and, in postmenopausal women, higher levels with longer oral
      contraceptive use and later-age-at and shorter-interval-since last birth. Lower
      anti-CA15.3 antibodies were associated with higher body mass and, in
      premenopausal women, more ovulatory cycles. Higher anti-CA15.3 and anti-CA125
      antibodies were associated with higher risk for mucinous EOC occurring >= 3 years
      from enrollment. Long-term risk for serous EOC was reduced in women with low
      CA125 and high anti-CA125 antibodies relative to women with low concentrations of
      both.Conclusions: We found general support for the hypothesis that anti-mucin
      antibody levels correlate with risk factors for EOC. Antibodies alone or in
      combinations with their antigen may predict longer term risk of specific EOC
      types.Impact: Anti-CA125 and anti-CA15.3 antibodies alone or in perspective of
      antigens may be informative in the pathogenesis of EOC subtypes, but less useful
      for informing risk for all EOC. Cancer Epidemiol Biomarkers Prev; 27(7); 790-804.
      (c)2018 AACR.

PMID- 29661802
TI  - Genetic unrelatedness of co-occurring pancreatic adenocarcinomas and IPMNs
      challenges current views of clinical management.

PMID- 29661803
TI  - Proton pump inhibitors and risk of gastric cancer in a case-control study.

PMID- 29661805
TI  - Slashed cost of hepatitis C drugs spurs drive to eliminate the disease.

PMID- 29661804
TI  - Combined use of two supervised learning algorithms to model sea turtle behaviours
      from tri-axial acceleration data.
AB  - Accelerometers are becoming ever more important sensors in animal-attached
      technology, providing data that allow determination of body posture and movement
      and thereby helping to elucidate behaviour in animals that are difficult to
      observe. We sought to validate the identification of sea turtle behaviours from
      accelerometer signals by deploying tags on the carapace of a juvenile loggerhead
      (Caretta caretta), an adult hawksbill (Eretmochelys imbricata) and an adult green
      turtle (Chelonia mydas) at Aquarium La Rochelle, France. We recorded tri-axial
      acceleration at 50 Hz for each species for a full day while two fixed cameras
      recorded their behaviours. We identified behaviours from the acceleration data
      using two different supervised learning algorithms, Random Forest and
      Classification And Regression Tree (CART), treating the data from the adult
      animals as separate from the juvenile data. We achieved a global accuracy of
      81.30% for the adult hawksbill and green turtle CART model and 71.63% for the
      juvenile loggerhead, identifying 10 and 12 different behaviours, respectively.
      Equivalent figures were 86.96% for the adult hawksbill and green turtle Random
      Forest model and 79.49% for the juvenile loggerhead, for the same behaviours. The
      use of Random Forest combined with CART algorithms allowed us to understand the
      decision rules implicated in behaviour discrimination, and thus remove or group
      together some 'confused' or under--represented behaviours in order to get the
      most accurate models. This study is the first to validate accelerometer data to
      identify turtle behaviours and the approach can now be tested on other captive
      sea turtle species.

PMID- 29661807
TI  - Genetically Engineered Mouse Models of Prostate Cancer in the Postgenomic Era.
AB  - Recent genomic sequencing analyses have unveiled the spectrum of genomic
      alterations that occur in primary and advanced prostate cancer, raising the
      question of whether the corresponding genes are functionally relevant for
      prostate tumorigenesis, and whether such functions are associated with particular
      disease stages. In this review, we describe genetically engineered mouse models
      (GEMMs) of prostate cancer, focusing on those that model genomic alterations
      known to occur in human prostate cancer. We consider whether the phenotypes of
      GEMMs based on gain or loss of function of the relevant genes provide reliable
      counterparts to study the predicted consequences of the corresponding genomic
      alterations as occur in human prostate cancer, and we discuss exceptions in which
      the GEMMs do not fully emulate the expected phenotypes. Last, we highlight future
      directions for the generation of new GEMMs of prostate cancer and consider how we
      can use GEMMs most effectively to decipher the biological and molecular
      mechanisms of disease progression, as well as to tackle clinically relevant
      questions.

PMID- 29661808
TI  - Immunization against Hepatitis A.
AB  - Worldwide, there are multiple formaldehyde-inactivated and at least two live
      attenuated hepatitis A vaccines now in clinical use. The impressive
      immunogenicity of inactivated vaccines is reflected in rapid seroconversion
      rates, enabling both preexposure and postexposure prophylaxis. Universal
      childhood vaccination programs targeting young children have led to significant
      drops in the incidence of hepatitis A both in toddlers and in susceptible
      nonimmune adults in regions with intermediate endemicity for hepatitis A.
      Although the safety of inactivated vaccines is well established, further studies
      are needed concerning the implications of fecal virus shedding by recipients of
      attenuated vaccines, as well as the long-term persistence of immune memory in
      children receiving novel immunization schedules consisting of single doses of
      inactivated vaccines.

PMID- 29661806
TI  - Daclizumab Therapy for Multiple Sclerosis.
AB  - Daclizumab is a humanized monoclonal antibody that prevents formation of high
      affinity interleukin (IL)-2 receptor (IL-2R). Because activated T cells up
      regulate high-affinity IL-2R and IL-2 is used to grow activated T cells in vitro,
      daclizumab was envisioned to selectively inhibit activated T cells. However, the
      mechanism of action (MOA) of daclizumab is surprisingly broad and it includes
      many unanticipated effects on innate immunity. Specifically, daclizumab modulates
      the development of innate lymphoid cells, leading to expansion of
      immunoregulatory CD56bright natural killer (NK) cells. Activated CD56bright NK
      cells migrate to the intrathecal compartment in multiple sclerosis (MS) and
      regulate autoreactive T cells via cytotoxicity. Finally, daclizumab also
      restricts initial steps of T-cell activation by blocking trans-presentation of IL
      2 by dendritic cells to antigen-specific T cells. In conclusion, daclizumab has
      complex immunomodulatory effects with resultant inhibition of central nervous
      system inflammation in MS.

PMID- 29661809
TI  - The Multiple Roles of B Cells in Multiple Sclerosis and Their Implications in
      Multiple Sclerosis Therapies.
AB  - Increasing evidence has suggested that both antibody-dependent and antibody
      independent functions of B cells are involved in multiple sclerosis (MS). The
      contrasting results of distinct B-cell targeting therapies in MS patients
      underscores the importance of elucidating these multiple B-cell functions. In
      this review, we discuss the generation of autoreactive B cells, migration of B
      cells into the central nervous system (CNS), and how different functions of B
      cells may contribute to MS disease activity and potentially mitigation in both
      the periphery and CNS compartments. In addition, we propose several future
      therapeutic strategies that may better target/shape B-cell responses for long
      term treatment of MS.

PMID- 29661810
TI  - Metastases in Prostate Cancer.
AB  - Prostate cancer (PCa) prognosis and clinical outcome is directly dependent on
      metastatic occurrence. The bone microenvironment is a favorable metastatic niche.
      Different biological processes have been suggested to contribute to the
      osteotropism of PCa such as hemodynamics, bone-specific signaling interactions,
      and the "seed and soil" hypothesis. However, prevalence of disseminating tumor
      cells in the bone is not proportional to the actual occurrence of metastases, as
      not all patients will develop bone metastases. The fate and tumor-reforming
      ability of a metastatic cell is greatly influenced by the microenvironment. In
      this review, the molecular mechanisms of bone and soft-tissue metastasis in PCa
      are discussed. Specific attention is dedicated to the residual disease, novel
      approaches, and animal models used in oncological translational research are
      illustrated.

PMID- 29661811
TI  - Murine Models of Hepatitis A Virus Infection.
AB  - Mechanistic analyses of hepatitis A virus (HAV)-induced pathogenesis have long
      been thwarted by the lack of tractable small animal models that recapitulate
      disease observed in humans. Several approaches have shown success, including
      infection of chimeric mice with human liver cells. Other recent studies show that
      HAV can replicate to high titer in mice lacking expression of the type I
      interferon (IFN) receptor (IFN-alpha/beta receptor) or mitochondrial antiviral
      signaling (MAVS) protein. Mice deficient in the IFN receptor show critical
      features of type A hepatitis in humans when challenged with human HAV, including
      histological evidence of liver damage, leukocyte infiltration, and the release of
      liver enzymes into blood. Acute pathogenesis is caused by MAVS-dependent
      signaling that leads to intrinsic apoptosis of hepatocytes.

PMID- 29661812
TI  - Resisting influence from agri-food industries on Canada's new food guide.

PMID- 29661813
TI  - Quality primary health care will drive the realization of universal health
      coverage.

PMID- 29661815
TI  - Why strengthening primary health care is essential to achieving universal health
      coverage.

PMID- 29661814
TI  - Psychometric findings and normative values for the CLEFT-Q based on 2434 children
      and young adult patients with cleft lip and/or palate from 12 countries.
AB  - BACKGROUND: Patients with cleft lip and/or palate can undergo numerous procedures
      to improve appearance, speech, dentition and hearing. We developed a cleft
      specific patient-reported outcome instrument to facilitate rigorous international
      measurement and benchmarking. METHODS: Data were collected from patients aged 8
      29 years with cleft lip and/or palate at 30 hospitals in 12 countries between
      October 2014 and November 2016. Rasch measurement theory analysis was used to
      refine the scales and to examine reliability and validity. Normative CLEFT-Q
      values were computed for age, sex and cleft type. RESULTS: Analysis led to the
      refinement of an eating and drinking checklist and 12 scales measuring appearance
      (of the face, nose, nostrils, teeth, lips, jaws and cleft lip scar), health
      related quality of life (psychological, social, school, speech distress) and
      speech function. All scales met the requirements of the Rasch model. Analysis to
      explore differential item functioning by age, sex and country provided evidence
      to support the use of a common scoring algorithm for each scale for international
      use. Lower (worse) scores on CLEFT-Q scales were associated with having a speech
      problem, being unhappy with facial appearance, and needing future cleft-related
      treatments, providing evidence of construct validity. Normative values for age,
      sex and cleft type showed poorer outcomes associated with older age, female sex
      and having a visible cleft. INTERPRETATION: The CLEFT-Q represents a rigorously
      developed instrument that can be used internationally to collect and compare
      evidence-based outcomes data from patients aged 8-29 years of age with cleft lip
      and/or palate.

PMID- 29661816
TI  - Mycotic aneurysm formation after bacillus Calmette-Guerin instillation for
      recurrent bladder cancer.

PMID- 29661817
TI  - Powassan virus - an emerging public health concern.

PMID- 29661818
TI  - Canada's future health care system.

PMID- 29661819
TI  - Whole-family treatment of neonatal abstinence syndrome.

PMID- 29661820
TI  - Rise of women in medicine not matched by leadership roles.

PMID- 29661821
TI  - Review calls for major overhaul of federally funded health organizations.

PMID- 29661822
TI  - Chronic pain associations struggle to raise awareness of "silent epidemic".

PMID- 29661823
TI  - Cutting Edge: Blockade of Inhibitor of Apoptosis Proteins Sensitizes Neutrophils
      to TNF- but Not Lipopolysaccharide-Mediated Cell Death and IL-1beta Secretion.
AB  - The mammalian inhibitor of apoptosis proteins (IAPs) are key regulators of cell
      death and inflammation. A major function of IAPs is to block the formation of a
      cell death-inducing complex, termed the ripoptosome, which can trigger caspase-8
      dependent apoptosis or caspase-independent necroptosis. Recent studies report
      that upon TLR4 or TNF receptor 1 (TNFR1) signaling in macrophages, the
      ripoptosome can also induce NLRP3 inflammasome formation and IL-1beta maturation.
      Whether neutrophils have the capacity to assemble a ripoptosome to induce cell
      death and inflammasome activation during TLR4 and TNFR1 signaling is unclear. In
      this study, we demonstrate that murine neutrophils can signal via TNFR1-driven
      ripoptosome assembly to induce both cell death and IL-1beta maturation. However,
      unlike macrophages, neutrophils suppress TLR4-dependent cell death and NLRP3
      inflammasome activation during IAP inhibition via deficiencies in the CD14/TRIF
      arm of TLR4 signaling.

PMID- 29661824
TI  - Development of Dengue Virus Serotype-Specific NS1 Capture Assays for the Rapid
      and Highly Sensitive Identification of the Infecting Serotype in Human Sera.
AB  - Dengue fever can be caused by one of four distinct dengue virus (DENV) serotypes
      that cocirculate in many parts of the world. Point of care serotype-specific
      nonstructural protein-1 (NS1) capture assays for the rapid serotyping of DENV in
      human sera would greatly support epidemiological surveillance and potentially
      also prognosis in individual patients. To ensure both serotype specificity and
      broad coverage of variants within serotypes, we have applied an innovative
      approach for the generation and selection of serotype-specific anti-NS1 mAbs. To
      elicit mAbs against conformational epitopes, NMRI mice were immunized with living
      HEK 293 transfectants expressing the native target Ags in multiple display on the
      cell surface. For each serotype, three different NS1 sequence variants were
      sequentially used for immunization of mice, hybridoma selection, and capture
      assay development, respectively. Selection of optimal combinations of capturing
      and detecting mAbs yielded highly sensitive and specific NS1 serotyping ELISAs
      (st-ELISAs) for the four serotypes. st-ELISA testing of 41 dengue patient sera
      showed a 100% concordance with the serotype determined by serotype-specific
      reverse transcriptase real-time quantitative PCR. The respective NS1 variants
      could be detected for ~10 d after the onset of illness. Ab-dependent enhancement
      of DENV infections may be associated with a specific range of pre-existing anti
      DENV serological Ab titers. Testing of patient sera with the developed st-ELISAs
      will not only be useful for epidemiological studies and surveillance, but it may
      also help to develop and validate assays that can distinguish protective versus
      enhancing Ab responses for risk assessment for the development of severe dengue
      disease in individual patients.

PMID- 29661825
TI  - NKp46 Calibrates Tumoricidal Potential of Type 1 Innate Lymphocytes by Regulating
      TRAIL Expression.
AB  - NK cells are a subset of group 1 innate lymphocytes that recognize and eliminate
      virus-infected and transformed cells. During the course of their development, NK
      cells acquire a repertoire of activating and inhibitory receptors, which
      ultimately define their reactivity against target cells. The array of receptors
      and their specificity during early developmental stages will control and imprint
      functional properties of NK cells, a process known as "NK cell education." Innate
      lymphoid cells (ILCs) are a diverse group of lymphocytes, which, like NK cells,
      do not rely on somatically rearranged Ag receptors for recognition. Among ILC
      subsets, ILC1s are most like NK cells functionally. Prototypic ILC1s reside in
      the liver, and a large part of their function is attributed to the expression of
      TRAIL, a TNF superfamily member with a well-documented antitumor activity. In
      this article, we show that TRAIL expression on mouse ILC1s is controlled by an
      activating receptor NKp46, which has been previously shown to control NK cell
      education. In the absence of NKp46, ILC1s fail to express normal levels of TRAIL
      on the surface, which results in diminished cytotoxicity toward TRAIL receptor
      positive targets. To our knowledge, these findings provide the first evidence of
      a role of NKp46 in ILC1s that calibrates their antitumor response.

PMID- 29661826
TI  - Tumor Tolerance-Promoting Function of Regulatory T Cells Is Optimized by CD28,
      but Strictly Dependent on Calcineurin.
AB  - Regulatory T cells (Treg) restrain immune responses against malignant tumors, but
      their global depletion in cancer patients will likely be limited by systemic
      autoimmune toxicity. Instead, approaches to "tune" their activities may allow for
      preferential targeting of tumor-reactive Treg. Although Ag recognition regulates
      Treg function, the roles of individual TCR-dependent signaling pathways in
      enabling Treg to promote tumor tolerance are not well characterized. In this
      study, we examined in mouse tumor models the role of calcineurin, a key mediator
      of TCR signaling, and the role of the costimulatory receptor CD28 in the
      differentiation of resting central Treg into effector Treg endowed with tumor
      tropism. We find that calcineurin, although largely dispensable for suppressive
      activity in vitro, is essential for upregulation of ICOS and CTLA-4 in Treg, as
      well as for expression of chemokine receptors driving their accumulation in
      tumors. In contrast, CD28 is not critical, but optimizes the formation of tumor
      homing Treg and their fitness in tumor tissue. Accordingly, although deletion of
      either CnB or CD28 strongly impairs Treg-mediated tumor tolerance, lack of CnB
      has an even more pronounced impact than lack of CD28. Hence, our studies reveal
      distinct roles for what has classically been defined as signal 1 and signal 2 of
      conventional T cell activation in the context of Treg-mediated tumor tolerance.

PMID- 29661827
TI  - Oral NaHCO3 Activates a Splenic Anti-Inflammatory Pathway: Evidence That
      Cholinergic Signals Are Transmitted via Mesothelial Cells.
AB  - We tested the hypothesis that oral NaHCO3 intake stimulates splenic anti
      inflammatory pathways. Following oral NaHCO3 loading, macrophage polarization was
      shifted from predominantly M1 (inflammatory) to M2 (regulatory) phenotypes, and
      FOXP3+CD4+ T-lymphocytes increased in the spleen, blood, and kidneys of rats.
      Similar anti-inflammatory changes in macrophage polarization were observed in the
      blood of human subjects following NaHCO3 ingestion. Surprisingly, we found that
      gentle manipulation to visualize the spleen at midline during surgical laparotomy
      (sham splenectomy) was sufficient to abolish the response in rats and resulted in
      hypertrophy/hyperplasia of the capsular mesothelial cells. Thin collagenous
      connections lined by mesothelial cells were found to connect to the capsular
      mesothelium. Mesothelial cells in these connections stained positive for the pan
      neuronal marker PGP9.5 and acetylcholine esterase and contained many
      ultrastructural elements, which visually resembled neuronal structures. Both
      disruption of the fragile mesothelial connections or transection of the vagal
      nerves resulted in the loss of capsular mesothelial acetylcholine esterase
      staining and reduced splenic mass. Our data indicate that oral NaHCO3 activates a
      splenic anti-inflammatory pathway and provides evidence that the signals that
      mediate this response are transmitted to the spleen via a novel neuronal-like
      function of mesothelial cells.

PMID- 29661829
TI  - MicroRNA-27b Modulates Inflammatory Response and Apoptosis during Mycobacterium
      tuberculosis Infection.
AB  - Mycobacterium tuberculosis poses a significant global health threat. MicroRNAs
      play an important role in regulating host anti-mycobacterial defense; however,
      their role in apoptosis-mediated mycobacterial elimination and inflammatory
      response remains unclear. In this study, we explored the role of microRNA-27b
      (miR-27b) in murine macrophage responses to M. tuberculosis infection. We
      uncovered that the TLR-2/MyD88/NF-kappaB signaling pathway induced the expression
      of miR-27b and miR-27b suppressed the production of proinflammatory factors and
      the activity of NF-kappaB, thereby avoiding an excessive inflammation during M.
      tuberculosis infection. Luciferase reporter assay and Western blotting showed
      that miR-27b directly targeted Bcl-2-associated athanogene 2 (Bag2) in
      macrophages. Overexpression of Bag2 reversed miR-27b-mediated inhibition of the
      production of proinflammatory factors. In addition, miR-27b increased p53
      dependent cell apoptosis and the production of reactive oxygen species and
      decreased the bacterial burden. We also showed that Bag2 interacts with p53 and
      negatively regulates its activity, thereby controlling cell apoptosis and
      facilitating bacterial survival. In summary, we revealed a novel role of the miR
      27b/Bag2 axis in the regulation of inflammatory response and apoptosis and
      provide a potential molecular host defense mechanism against mycobacteria.

PMID- 29661828
TI  - Nasopharyngeal Exposure to Streptococcus pneumoniae Induces Extended Age
      Dependent Protection against Pulmonary Infection Mediated by Antibodies and
      CD138+ Cells.
AB  - Streptococcus pneumoniae commonly resides asymptomatically in the nasopharyngeal
      (NP) cavity of healthy individuals but can cause life-threatening pulmonary and
      systemic infections, particularly in the elderly. NP colonization results in a
      robust immune response that protects against invasive infections. However, the
      duration, mechanism, and cellular component of such responses are poorly
      understood. In this study, we found that repeated NP exposure of mice to S.
      pneumoniae TIGR4 strain results in pneumococcal-specific Ab responses that
      protect against lethal lung challenge. Abs were necessary and sufficient for
      protection because Ab-deficient MUMT mice did not develop postexposure
      protection, only becoming resistant to lung infection after transfer of immune
      sera from NP-exposed mice. T cells contributed to immunity at the time of NP
      exposure, but neither CD4+ nor CD8+ T cells were required. The protective
      activity was detectable 20 wk after exposure and was maintained in irradiated
      mice, suggesting involvement of long-lived Ab-secreting cells (ASC), which are
      radioresistant and secrete Abs for extended periods of time in the absence of T
      cells or persistent Ag. CD138+ bone marrow cells, likely corresponding to long
      lived ASC, were sufficient to confer protection. NP exposure of aged mice failed
      to protect against subsequent lung infection despite eliciting a robust Ab
      response. Furthermore, transfer of CD138+ bone marrow cells or sera from NP
      exposed old mice failed to protect naive young mice. These findings suggest that
      NP exposure elicits extended protection against pneumococcal lung infection by
      generating long-lived CD138+ ASC and that the protective efficacy of these
      responses declines with age.

PMID- 29661830
TI  - Sustained Adrenergic Signaling Promotes Intratumoral Innervation through BDNF
      Induction.
AB  - Mounting clinical and preclinical evidence supports a key role for sustained
      adrenergic signaling in the tumor microenvironment as a driver of tumor growth
      and progression. However, the mechanisms by which adrenergic neurotransmitters
      are delivered to the tumor microenvironment are not well understood. Here we
      present evidence for a feed-forward loop whereby adrenergic signaling leads to
      increased tumoral innervation. In response to catecholamines, tumor cells
      produced brain-derived neurotrophic factor (BDNF) in an ADRB3/cAMP/Epac/JNK
      dependent manner. Elevated BDNF levels in the tumor microenvironment increased
      innervation by signaling through host neurotrophic receptor tyrosine kinase 2
      receptors. In patients with cancer, high tumor nerve counts were significantly
      associated with increased BDNF and norepinephrine levels and decreased overall
      survival. Collectively, these data describe a novel pathway for tumor
      innervation, with resultant biological and clinical implications.Significance:
      Sustained adrenergic signaling promotes tumor growth and metastasis through BDNF
      mediated tumoral innervation. Cancer Res; 78(12); 3233-42. (c)2018 AACR.

PMID- 29661831
TI  - Differential Effects of Estrogen Receptor beta Isoforms on Glioblastoma
      Progression.
AB  - The estrogen receptor beta (ERbeta) functions as a tumor suppressor in
      glioblastoma (GBM) cells. However, the in vivo significance of endogenous ERbeta
      and the roles of its isoforms in GBM are incompletely understood. Using ERbeta
      isoform-specific PCR screening, we found that GBM cells predominantly express
      ERbeta1 and ERbeta5, along with low levels of ERbeta2 and ERbeta4. We observed
      greater ERbeta5 expression in higher grades of glioma than in lower grades. In
      CRISPR-based ERbeta knockout (KO) cells and ERbeta KO cells uniquely expressing
      ERbeta1 or ERbeta5 only, ERbeta1 significantly reduced proliferation. Compared
      with parental GBM cells, ERbeta KO cells exhibited high migratory and invasive
      potentials, and reexpression of ERbeta1 resulted in the reduction of this
      phenotype. Interestingly, ERbeta5 expression increased foci formation and
      anchorage-independent growth of NIH3T3 cells and increased motile structure
      formation, including filopodia and ruffles in GBM cells. Only ERbeta1-expressing
      tumors resulted in longer mouse survival. RNA-Seq analysis revealed unique
      pathways modulated by ERbeta1 and ERbeta5. Compared with ERbeta KO cells, ERbeta1
      cells exhibited lower activation of mTOR signaling molecules, including p-mTOR, p
      S6K, and p-S6, and ERbeta5-expressing cells had enhanced mTOR downstream
      signaling. Unique proteins including several that function as regulators of mTOR,
      immunomodulatory, and apoptosis pathways bound to ERbeta1 and ERbeta5 isoforms.
      Our work confirms the tumor-suppressive potential of ERbeta1 and reveals the
      acquired oncogenic ability of ERbeta5 in GBM cells. ERbeta isoform status and
      their unique interactions with oncogenic pathways may have important implications
      in GBM progression.Significance: These findings suggest that only ERbeta isoform
      1 has tumor suppressor function in GBM and that ERbeta isoform switching
      contributes to GBM progression. Cancer Res; 78(12); 3176-89. (c)2018 AACR.

PMID- 29661832
TI  - Kinase activity in the olfactory bulb is required for odor memory consolidation.
AB  - Long-term fear memory formation in the hippocampus and neocortex depends upon
      brain-derived neurotrophic factor (BDNF) signaling after acquisition.
      Incremental, appetitive odor discrimination learning is thought to depend
      substantially on the differentiation of adult-born neurons within the olfactory
      bulb (OB)-a process that is closely associated with BDNF signaling. We sought to
      elucidate the role of neurotrophin signaling within the OB on odor memory
      consolidation. Male mice were trained on odor-reward associative discriminations
      after bilateral infusion of the kinase inhibitor K252a, or vehicle control, into
      the OB. K252a is a partially selective inhibitor of tyrosine kinase (Trk)
      receptors, including the TrkB receptor for BDNF, though it also inhibits other
      plasticity-related kinases such as PKC and CaMKII/IV. K252a infusion into the OB
      did not impair odor acquisition or short-term (2 h) memory for the learned
      discriminations, but significantly impaired long-term (48 h) odor memory (LTM).
      This LTM deficit also was associated with reduced selectivity for the conditioned
      odorant in a reward-seeking digging task. Infusions of K252a immediately prior to
      testing did not impair LTM recall. These results indicate that kinase activation
      in the OB is required for the consolidation of odor memory of incrementally
      acquired information.

PMID- 29661833
TI  - NO is required for memory formation and expression of memory, and for minor
      behavioral changes during training with inedible food in Aplysia.
AB  - A learning experience may lead to changes in behavior during the experience, and
      also to memory expressed at a later time. Are signals causing changes in behavior
      during the learning experience related to the formation and expression of memory?
      We examined this question, using learning that food is inedible in Aplysia
      Treatment of an isolated buccal ganglia preparation with an NO donor elicited
      rejection-like motor programs. Rejection initiated by NO production is consistent
      with aspects of behavioral changes seen while animals learn, and with memory
      formation. Nonetheless, applying the NO donor during training had only minor
      effects on behavior during the training, and did not improve memory, indicating
      that the induction of rejection in the buccal ganglia is unlikely to be the means
      by which NO during training contributes to memory formation. Block of NO during
      memory retrieval prevented the expression of memory, as measured by a lack of
      savings in time to stop responding to food. Applying an NO donor to the cerebral
      ganglion while eliciting fictive feeding inhibited the expression of feeding
      activity, indicating that some NO effects on memory consolidation and on
      expression of memory may be via effects on the cerebral ganglion.

PMID- 29661834
TI  - miR-132 couples the circadian clock to daily rhythms of neuronal plasticity and
      cognition.
AB  - The microRNA miR-132 serves as a key regulator of a wide range of plasticity
      associated processes in the central nervous system. Interestingly, miR-132
      expression has also been shown to be under the control of the circadian timing
      system. This finding, coupled with work showing that miR-132 is expressed in the
      hippocampus, where it influences neuronal morphology and memory, led us to test
      the idea that daily rhythms in miR-132 within the forebrain modulate cognition as
      a function of circadian time. Here, we show that hippocampal miR-132 expression
      is gated by the time-of-day, with peak levels occurring during the circadian
      night. Further, in miR-132 knockout mice and in transgenic mice, where miR-132 is
      constitutively expressed under the control of the tetracycline regulator system,
      we found that time-of-day dependent memory recall (as assessed via novel object
      location and contextual fear conditioning paradigms) was suppressed. Given that
      miRNAs exert their functional effects via the suppression of target gene
      expression, we examined the effects that transgenic miR-132 manipulations have on
      MeCP2 and Sirt1-two miR-132 targets that are associated with neuronal plasticity
      and cognition. In mice where miR-132 was either knocked out, or transgenically
      expressed, rhythmic expression of MeCP2 and Sirt1 was suppressed. Taken together,
      these results raise the prospect that miR-132 serves as a key route through which
      the circadian timing system imparts a daily rhythm on cognitive capacity.

PMID- 29661835
TI  - Sexual differentiation of contextual fear responses.
AB  - Development and sex differentiation impart an organizational influence on the
      neuroanatomy and behavior of mammalian species. Prior studies suggest that brain
      regions associated with fear motivated defensive behavior undergo a protracted
      and sex-dependent development. Outside of adult animals, evidence for
      developmental sex differences in conditioned fear is sparse. Here, we examined in
      male and female Long-Evans rats how developmental age and sex affect the long
      term retention and generalization of Pavlovian fear responses. Experiments 1 and
      2 describe under increasing levels of aversive learning (three and five trials)
      the long-term retrieval of cued and context fear in preadolescent (P24 and P33),
      periadolescent (P37), and adult (P60 and P90) rats. Experiments 3 and 4 examined
      contextual processing under minimal aversive learning (1 trial) procedures in
      infant (P19, P21), preadolescent (P24), and adult (P60) rats. Here, we found that
      male and female rats display a divergent developmental trajectory in the
      expression of context-mediated freezing, such that context fear expression in
      males tends to increase toward adulthood, while females displayed an opposite
      pattern of decreasing context fear expression toward adulthood. Longer (14 d)
      retention intervals produced an overall heightened context fear expression
      relative to shorter (1 d) retention intervals an observation consistent with fear
      incubation. Male, but not Female rats showed increasing generalization of context
      fear across development. Collectively, these findings provide an initial
      demonstration that sexual differentiation of contextual fear conditioning emerges
      prior to puberty and follows a distinct developmental trajectory toward adulthood
      that strikingly parallels sex differences in the etiology and epidemiology of
      anxiety and trauma- and stressor-related disorders.

PMID- 29661837
TI  - Sodium Handling by the Blood Vessel Wall: Critical for Hypertension Development.

PMID- 29661836
TI  - Fear memory consolidation in sleep requires protein kinase A.
AB  - It is well established that protein kinase A (PKA) is involved in hippocampal
      dependent memory consolidation. Sleep is also known to play an important role in
      this process. However, whether sleep-dependent memory consolidation involves PKA
      activation has not been clearly determined. Using behavioral observation, animals
      were categorized into sleep and awake groups. We show that intrahippocampal
      injections of the PKA inhibitor Rp-cAMPs in post-contextual fear conditioning
      sleep produced a suppression of long-term fear memory, while injections of Rp
      cAMPs during an awake state, at a similar time point, had no effect. In contrast,
      injections of the PKA activator Sp-cAMPs in awake state, rescued sleep
      deprivation-induced memory impairments. These results suggest that following
      learning, PKA activation specifically in sleep is required for the consolidation
      of long-term memory.

PMID- 29661839
TI  - Targeting Mitochondria in Age-Related Vascular Changes: A New Arrow to the Bow of
      Antioxidant Treatment?

PMID- 29661838
TI  - Chronic Supplementation With a Mitochondrial Antioxidant (MitoQ) Improves
      Vascular Function in Healthy Older Adults.
AB  - : Excess reactive oxygen species production by mitochondria is a key mechanism of
      age-related vascular dysfunction. Our laboratory has shown that supplementation
      with the mitochondrial-targeted antioxidant MitoQ improves vascular endothelial
      function by reducing mitochondrial reactive oxygen species and ameliorates
      arterial stiffening in old mice, but the effects in humans are unknown. Here, we
      sought to translate our preclinical findings to humans and determine the safety
      and efficacy of MitoQ. Twenty healthy older adults (60-79 years) with impaired
      endothelial function (brachial artery flow-mediated dilation <6%) underwent 6
      weeks of oral supplementation with MitoQ (20 mg/d) or placebo in a randomized,
      placebo-controlled, double-blind, crossover design study. MitoQ was well
      tolerated, and plasma MitoQ was higher after the treatment versus placebo period
      (P<0.05). Brachial artery flow-mediated dilation was 42% higher after MitoQ
      versus placebo (P<0.05); the improvement was associated with amelioration of
      mitochondrial reactive oxygen species-related suppression of endothelial function
      (assessed as the increase in flow-mediated dilation with acute, supratherapeutic
      MitoQ [160 mg] administration; n=9; P<0.05). Aortic stiffness (carotid-femoral
      pulse wave velocity) was lower after MitoQ versus placebo (P<0.05) in
      participants with elevated baseline levels (carotid-femoral pulse wave velocity
      >7.60 m/s; n=11). Plasma oxidized LDL (low-density lipoprotein), a marker of
      oxidative stress, also was lower after MitoQ versus placebo (P<0.05). Participant
      characteristics, endothelium-independent dilation (sublingual nitroglycerin), and
      circulating markers of inflammation were not different (all P>0.1). These
      findings in humans extend earlier preclinical observations and suggest that MitoQ
      and other therapeutic strategies targeting mitochondrial reactive oxygen species
      may hold promise for treating age-related vascular dysfunction. CLINICAL TRIAL
      REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02597023.

PMID- 29661840
TI  - Therapeutic Potential of a Novel Necrosis Inhibitor, 7-Amino-Indole, in
      Myocardial Ischemia-Reperfusion Injury.
AB  - Opening of mitochondrial permeability transition pore and Ca2+ overload are main
      contributors to myocardial ischemia-reperfusion injury, which paradoxically
      causes a wide variety of myocardial damage. We investigated the protective role
      of a novel necrosis inhibitor (NecroX-7; NecX) against myocardial ischemia
      reperfusion injury using in vitro and in vivo models. H9C2 rat cardiomyoblasts
      and neonatal cardiomyocytes were exposed to hypoxia-reoxygenation stress after
      pre-treatment with NecX, vitamin C, a combination of vitamin C and E, N
      acetylcysteine, an apoptosis inhibitor (Z-VAD-fmk), or cyclosporine A. The main
      mechanism of cell death after hypoxia-reoxygenation stress was not apoptosis but
      necrosis, which was prevented by NecX. Protective effect of NecX was based on its
      potent reactive oxygen species scavenging activity, especially on mitochondrial
      reactive oxygen species. NecX preserved mitochondrial membrane potential through
      prevention of Ca2+ influx and inhibition of mitochondrial permeability transition
      pore opening, which was more potent than that by cyclosporine A. Using Sprague
      Dawley rats exposed to myocardial ischemia for 45 minutes followed by
      reperfusion, we compared therapeutic efficacies of NecX with cyclosporine A,
      vitamin C, a combination of vitamin C and E, and 5% dextrose, each administered 5
      minutes before reperfusion. NecX markedly inhibited myocardial necrosis and
      reduced fibrotic area to a greater extent than did cyclosporine A and other
      treated groups. In addition, NecX preserved systolic function and prevented
      pathological dilatory remodeling of left ventricle. The novel necrosis inhibitor
      has a significant protective effect against myocardial ischemia-reperfusion
      injury through inhibition of mitochondrial permeability transition pore opening,
      indicating that it is a promising candidate for cardioprotective adjunctive
      measure on top of reperfusion therapy.

PMID- 29661841
TI  - Angiotensin II Short-Loop Feedback: Is There a Role of Ang II for the Regulation
      of the Renin System In Vivo?
AB  - The activity of the renin-angiotensin-aldosterone system is triggered by the
      release of the protease renin from the kidneys, which in turn is controlled in
      the sense of negative feedback loops. It is widely assumed that Ang II
      (angiotensin II) directly inhibits renin expression and secretion via a short
      loop feedback by an effect on renin-producing cells (RPCs) mediated by AT1 (Ang
      II type 1) receptors. Because the concept of such a direct short-loop negative
      feedback control, which originates mostly from in vitro experiments, has not yet
      been systematically proven in vivo, we aimed to test the validity of this concept
      by studying the regulation of renin synthesis and secretion in mice lacking Ang
      II-AT1 receptors on RPCs. We found that RPCs of the kidney express Ang II-AT1
      receptors. Mice with conditional deletion of Ang II-AT1 receptors in RPCs were
      normal with regard to the number of renin cells, renal renin mRNA, and plasma
      renin concentrations. Renin expression and secretion of these mice responded to
      Ang I (angiotensin I)-converting enzyme inhibition and to Ang II infusion like in
      wild-type (WT) controls. In summary, we did not obtain evidence that Ang II-AT1
      receptors on RPCs are of major relevance for the normal regulation of renin
      expression and secretion in mice. Therefore, we doubt the existence of a direct
      negative feedback function of Ang II on RPCs.

PMID- 29661842
TI  - Accounting for Genotype-by-Environment Interactions and Residual Genetic
      Variation in Genomic Selection for Water-Soluble Carbohydrate Concentration in
      Wheat.
AB  - Abiotic stress tolerance traits are often complex and recalcitrant targets for
      conventional breeding improvement in many crop species. This study evaluated the
      potential of genomic selection to predict water-soluble carbohydrate
      concentration (WSCC), an important drought tolerance trait, in wheat under field
      conditions. A panel of 358 varieties and breeding lines constrained for maturity
      was evaluated under rainfed and irrigated treatments across two locations and two
      years. Whole-genome marker profiles and factor analytic mixed models were used to
      generate genomic estimated breeding values (GEBVs) for specific environments and
      environment groups. Additive genetic variance was smaller than residual genetic
      variance for WSCC, such that genotypic values were dominated by residual genetic
      effects rather than additive breeding values. As a result, GEBVs were not
      accurate predictors of genotypic values of the extant lines, but GEBVs should be
      reliable selection criteria to choose parents for intermating to produce new
      populations. The accuracy of GEBVs for untested lines was sufficient to increase
      predicted genetic gain from genomic selection per unit time compared to
      phenotypic selection if the breeding cycle is reduced by half by the use of GEBVs
      in off-season generations. Further, genomic prediction accuracy depended on
      having phenotypic data from environments with strong correlations with target
      production environments to build prediction models. By combining high-density
      marker genotypes, stress-managed field evaluations, and mixed models that model
      simultaneously covariances among genotypes and covariances of complex trait
      performance between pairs of environments, we were able to train models with good
      accuracy to facilitate genetic gain from genomic selection.

PMID- 29661844
TI  - Complexes of plexin-A4 and plexin-D1 convey semaphorin-3C signals to induce
      cytoskeletal collapse in the absence of neuropilins.
AB  - Class-3 semaphorin guidance factors bind to receptor complexes containing
      neuropilin and plexin receptors. A semaphorin may bind to several receptor
      complexes containing somewhat different constituents, resulting in diverse
      effects on cell migration. U87MG glioblastoma cells express both neuropilins and
      the four class-A plexins. Here, we show that these cells respond to Sema3A or
      Sema3B by cytoskeletal collapse and cell contraction but fail to contract in
      response to Sema3C, Sema3D, Sema3G or Sema3E, even when class-A plexins are
      overexpressed in the cells. In contrast, expression of recombinant plexin-D1
      enabled contraction in response to these semaphorins. Surprisingly, unlike Sema3D
      and Sema3G, Sema3C also induced the contraction and repulsion of plexin-D1
      expressing U87MG cells in which both neuropilins were knocked out using
      CRISPR/Cas9. In the absence of neuropilins, the EC50 of Sema3C was 5.5 times
      higher, indicating that the neuropilins function as enhancers of plexin-D1
      mediated Sema3C signaling but are not absolutely required for Sema3C signal
      transduction. Interestingly, in the absence of neuropilins, plexin-A4 formed
      complexes with plexin-D1, and was required in addition to plexin-D1 to enable
      Sema3C-induced signal transduction.

PMID- 29661843
TI  - Functional Analysis of Hif1 Histone Chaperone in Saccharomyces cerevisiae.
AB  - The Hif1 protein in the yeast Saccharomyces cerevisie is an evolutionarily
      conserved H3/H4-specific chaperone and a subunit of the nuclear Hat1 complex that
      catalyzes the acetylation of newly synthesized histone H4. Hif1, as well as its
      human homolog NASP, has been implicated in an array of chromatin-related
      processes including histone H3/H4 transport, chromatin assembly and DNA repair.
      In this study, we elucidate the functional aspects of Hif1 Initially we establish
      the wide distribution of Hif1 homologs with an evolutionarily conserved pattern
      of four tetratricopeptide repeats (TPR) motifs throughout the major fungal
      lineages and beyond. Subsequently, through targeted mutational analysis, we
      demonstrate that the acidic region that interrupts the TPR2 is essential for Hif1
      physical interactions with the Hat1/Hat2-complex, Asf1, and with histones H3/H4.
      Furthermore, we provide evidence for the involvement of Hif1 in regulation of
      histone metabolism by showing that cells lacking HIF1 are both sensitive to
      histone H3 over expression, as well as synthetic lethal with a deletion of
      histone mRNA regulator LSM1 We also show that a basic patch present at the
      extreme C-terminus of Hif1 is essential for its proper nuclear localization.
      Finally, we describe a physical interaction with a transcriptional regulatory
      protein Spt2, possibly linking Hif1 and the Hat1 complex to transcription
      associated chromatin reassembly. Taken together, our results provide novel
      mechanistic insights into Hif1 functions and establish it as an important protein
      in chromatin-associated processes.

PMID- 29661846
TI  - The GET pathway can increase the risk of mitochondrial outer membrane proteins to
      be mistargeted to the ER.
AB  - Tail-anchored (TA) proteins are anchored to their corresponding membrane via a
      single transmembrane segment (TMS) at their C-terminus. In yeast, the targeting
      of TA proteins to the endoplasmic reticulum (ER) can be mediated by the guided
      entry of TA proteins (GET) pathway, whereas it is not yet clear how mitochondrial
      TA proteins are targeted to their destination. It has been widely observed that
      some mitochondrial outer membrane (MOM) proteins are mistargeted to the ER when
      overexpressed or when their targeting signal is masked. However, the mechanism of
      this erroneous sorting is currently unknown. In this study, we demonstrate the
      involvement of the GET machinery in the mistargeting of suboptimal MOM proteins
      to the ER. These findings suggest that the GET machinery can, in principle,
      recognize and guide mitochondrial and non-canonical TA proteins. Hence, under
      normal conditions, an active mitochondrial targeting pathway must exist that
      dominates the kinetic competition against other pathways.

PMID- 29661845
TI  - Lysosome enlargement during inhibition of the lipid kinase PIKfyve proceeds
      through lysosome coalescence.
AB  - Lysosomes receive and degrade cargo from endocytosis, phagocytosis and autophagy.
      They also play an important role in sensing and instructing cells on their
      metabolic state. The lipid kinase PIKfyve generates phosphatidylinositol-3,5
      bisphosphate to modulate lysosome function. PIKfyve inhibition leads to impaired
      degradative capacity, ion dysregulation, abated autophagic flux and a massive
      enlargement of lysosomes. Collectively, this leads to various physiological
      defects, including embryonic lethality, neurodegeneration and overt inflammation.
      The reasons for such drastic lysosome enlargement remain unclear. Here, we
      examined whether biosynthesis and/or fusion-fission dynamics contribute to
      swelling. First, we show that PIKfyve inhibition activates TFEB, TFE3 and MITF,
      enhancing lysosome gene expression. However, this did not augment lysosomal
      protein levels during acute PIKfyve inhibition, and deletion of TFEB and/or
      related proteins did not impair lysosome swelling. Instead, PIKfyve inhibition
      led to fewer but enlarged lysosomes, suggesting that an imbalance favouring
      lysosome fusion over fission causes lysosome enlargement. Indeed, conditions that
      abated fusion curtailed lysosome swelling in PIKfyve-inhibited cells.

PMID- 29661847
TI  - The Ajuba family protein Wtip regulates actomyosin contractility during
      vertebrate neural tube closure.
AB  - Ajuba family proteins are implicated in the assembly of cell junctions and have
      been reported to antagonize Hippo signaling in response to cytoskeletal tension.
      To assess the role of these proteins in actomyosin contractility, we examined the
      localization and function of Wtip, a member of the Ajuba family, in Xenopus early
      embryos. Targeted in vivo depletion of Wtip inhibited apical constriction in
      neuroepithelial cells and elicited neural tube defects. Fluorescent protein
      tagged Wtip showed predominant punctate localization along the cell junctions in
      the epidermis and a linear junctional pattern in the neuroectoderm. In cells
      undergoing Shroom3-induced apical constriction, the punctate distribution was
      reorganized into a linear pattern. Conversely, the linear junctional pattern of
      Wtip in neuroectoderm changed to a more punctate distribution in cells with
      reduced myosin II activity. The C-terminal fragment of Wtip physically associated
      with Shroom3 and interfered with Shroom3 activity and neural fold formation. We
      therefore propose that Wtip is a tension-sensitive cytoskeletal adaptor that
      regulates apical constriction during vertebrate neurulation.This article has an
      associated First Person interview with the first author of the paper.

PMID- 29661848
TI  - Mitochondrial cAMP exerts positive feedback on mitochondrial Ca2+ uptake via the
      recruitment of Epac1.
AB  - We have previously demonstrated in H295R adrenocortical cells that the Ca2+
      dependent production of mitochondrial cAMP (mt-cAMP) by the matrix soluble
      adenylyl cyclase (sAC; encoded by ADCY10) is associated with enhanced aldosterone
      production. Here, we examined whether mitochondrial sAC and mt-cAMP fine tune
      mitochondrial Ca2+ metabolism to support steroidogenesis. Reduction of mt-cAMP
      formation resulted in decelerated mitochondrial Ca2+ accumulation in intact cells
      during K+-induced Ca2+ signalling and also in permeabilized cells exposed to
      elevated perimitochondrial [Ca2+]. By contrast, treatment with the membrane
      permeable cAMP analogue 8-Br-cAMP, inhibition of phosphodiesterase 2 and
      overexpression of sAC in the mitochondrial matrix all intensified Ca2+ uptake
      into the organelle. Identical mt-cAMP dependence of mitochondrial Ca2+ uptake was
      also observed in HeLa cells. Importantly, the enhancing effect of mt-cAMP on Ca2+
      uptake was independent from both the mitochondrial membrane potential and Ca2+
      efflux, but was reduced by Epac1 (also known as RAPGEF3) blockade both in intact
      and in permeabilized cells. Finally, overexpression of sAC in the mitochondrial
      matrix potentiated aldosterone production implying that the observed positive
      feedback mechanism of mt-cAMP on mitochondrial Ca2+ accumulation may have a role
      in the rapid initiation of steroidogenesis.This article has an associated First
      Person interview with the first author of the paper.

PMID- 29661849
TI  - Feedback regulation by antagonistic epigenetic factors potentially maintains
      developmental homeostasis in Drosophila.
AB  - Drosophila Polycomb group (PcG) repressors confer epigenetically heritable
      silencing on key regulatory genes through histone H3 trimethylation on lysine 27
      (H3K27me3). How the silencing state withstands antagonistic activities from co
      expressed trithorax group (trxG) activators is unclear. Upon overexpression of
      Trx H3K4 methylase, to perturb the silenced state, we find a dynamic process
      triggered in a stepwise fashion to neutralize the inductive impacts from excess
      Trx. Shortly after Trx overexpression, there are global increases in H3K4
      trimethylation and RNA polymerase II phosphorylation, marking active
      transcription. Subsequently, these patterns diminish at the same time as the
      levels of Set1, an abundant H3K4 methylase involved in productive transcription,
      reduce. Concomitantly, the global H3K27me3 level is markedly reduced,
      corresponding to an increase in the amount of Utx demethylase. Finally, excess Pc
      repressive complex 1 (PRC1) is induced and located to numerous ectopic
      chromosomal sites independently of H3K27me3 and several key recruitment factors.
      The observation that PRC1 becomes almost completely colocalized with Trx suggests
      new aspects of recruitment and antagonistic interaction. We propose that these
      events represent a feedback circuitry ensuring the stability of the silenced
      state.

PMID- 29661850
TI  - Distinct 3' UTRs regulate the life-cycle-specific expression of two TCTP paralogs
      in Trypanosoma brucei.
AB  - The translationally controlled tumor protein (TCTP; also known as TPT1 in
      mammals) is highly conserved and ubiquitously expressed in eukaryotes. It is
      involved in growth and development, cell cycle progression, protection against
      cellular stresses and apoptosis, indicating the multifunctional role of the
      protein. Here, for the first time, we characterize the expression and function of
      TCTP in the human and animal pathogen, Trypanosoma brucei We identified two
      paralogs (TCTP1 and TCTP2) that are differentially expressed in the life cycle of
      the parasite. The genes have identical 5' untranslated regions (UTRs) and almost
      identical open-reading frames. The 3'UTRs differ substantially in sequence and
      length, and are sufficient for the exclusive expression of TCTP1 in procyclic-
      and TCTP2 in bloodstream-form parasites. Furthermore, we characterize which parts
      of the 3'UTR are needed for TCTP2 mRNA stability. RNAi experiments demonstrate
      that TCTP1 and TCTP2 expression is essential for normal cell growth in procyclic-
      and bloodstream-form parasites, respectively. Depletion of TCTP1 in the procyclic
      form cells leads to aberrant cell and mitochondrial organelle morphology, as well
      as enlarged, and a reduced number of, acidocalcisomes.

PMID- 29661853
TI  - Towards Prevention of Breast Cancer: What Are the Clinical Challenges?
AB  - The dramatic increase in breast cancer incidence compels a paradigm shift in our
      preventive efforts. There are several barriers to overcome before prevention
      becomes an established part of breast cancer management. The objective of this
      review is to identify the clinical challenges for improved breast cancer
      prevention and discuss current knowledge on breast cancer risk assessment
      methods, risk communication, ethics, and interventional efforts with the aim of
      covering the aspects relevant for a breast cancer prevention trial. Herein, the
      following five areas are discussed: (i) Adequate tools for identification of
      women at high risk of breast cancer suggestively entitled Prevent! Online. (ii)
      Consensus on the definition of high risk, which is regarded as mandatory for all
      risk communication and potential prophylactic interventions. (iii) Risk
      perception and communication regarding risk information. (iv) Potential ethical
      concerns relevant for future breast cancer prevention programs. (v) Risk-reducing
      programs involving multileveled prevention depending on identified risk. Taken
      together, devoted efforts from both policy makers and health care providers are
      warranted to improve risk assessment and risk counseling in women at risk for
      breast cancer to optimize the prevention of breast cancer. Cancer Prev Res;
      11(5); 255-64. (c)2018 AACR.

PMID- 29661852
TI  - Integrated Transcriptomic and Proteomic Analyses Suggest the Participation of
      Endogenous Protease Inhibitors in the Regulation of Protease Gene Expression in
      Helicoverpa armigera.
AB  - Insects adapt to plant protease inhibitors (PIs) present in their diet by
      differentially regulating multiple digestive proteases. However, mechanisms
      regulating protease gene expression in insects are largely enigmatic. Ingestion
      of multi-domain recombinant Capsicum annuum protease inhibitor-7 (CanPI-7)
      arrests growth and development of Helicoverpa armigera (Lepidoptera: Noctuidae).
      Using de novo RNA sequencing and proteomic analysis, we examined the response of
      H. armigera larvae fed on recombinant CanPI-7 at different time intervals. Here,
      we present evidence supporting a dynamic transition in H. armigera protease
      expression on CanPI-7 feeding with general down-regulation of protease genes at
      early time points (0.5 to 6 h) and significant up-regulation of specific trypsin,
      chymotrypsin and aminopeptidase genes at later time points (12 to 48 h). Further,
      coexpression of H. armigera endogenous PIs with several digestive protease genes
      were apparent. In addition to the differential expression of endogenous H.
      armigera PIs, we also observed a distinct novel isoform of endogenous PI in CanPI
      7 fed H. armigera larvae. Based on present and earlier studies, we propose
      potential mechanism of protease regulation in H. armigera and subsequent
      adaptation strategy to cope with anti-nutritional components of plants.

PMID- 29661854
TI  - Targeting Toll-like Receptors in Cancer Prevention.
AB  - There is a pressing need for the development of new prevention strategies for the
      most common worldwide malignancy, nonmelanoma skin cancer (NMSC), as sun
      protection efforts have not proven to be completely effective. Interestingly,
      despite the known circumstance that individuals undergoing chronic
      immunosuppression are at a substantially increased risk for developing NMSC, in
      this issue of Cancer Prevention Research, Blohm-Mangone and colleagues provide
      new evidence that topical application of the Toll-like receptor 4 (TLR4)
      antagonist resatorvid may be efficacious as a chemopreventive agent in NMSC
      specifically via blocking UV-induced inflammatory signaling. These new findings
      highlight a potentially delicate dichotomy between the role of innate immune
      receptors in the normal, protective immunosurveillance of damaged cells in the
      skin and the pathogenic UV-induced overstimulation of cutaneous inflammation that
      promotes photocarcinogenesis. Given the tremendous cancer burden incurred by
      NMSC, further exploration of the use of TLR4 antagonists in NMSC chemoprevention
      strategies is certainly warranted. Cancer Prev Res; 11(5); 251-4. (c)2018 AACRSee
      related article by Blohm-Mangone et al., p. 265.

PMID- 29661855
TI  - The heptad repeat domain 1 of Mitofusin has membrane destabilization function in
      mitochondrial fusion.
AB  - Mitochondria are double-membrane-bound organelles that constantly change shape
      through membrane fusion and fission. Outer mitochondrial membrane fusion is
      controlled by Mitofusin, whose molecular architecture consists of an N-terminal
      GTPase domain, a first heptad repeat domain (HR1), two transmembrane domains, and
      a second heptad repeat domain (HR2). The mode of action of Mitofusin and the
      specific roles played by each of these functional domains in mitochondrial fusion
      are not fully understood. Here, using a combination of in situ and in vitro
      fusion assays, we show that HR1 induces membrane fusion and possesses a conserved
      amphipathic helix that folds upon interaction with the lipid bilayer surface. Our
      results strongly suggest that HR1 facilitates membrane fusion by destabilizing
      the lipid bilayer structure, notably in membrane regions presenting lipid packing
      defects. This mechanism for fusion is thus distinct from that described for the
      heptad repeat domains of SNARE and viral proteins, which assemble as membrane
      bridging complexes, triggering close membrane apposition and fusion, and is more
      closely related to that of the C-terminal amphipathic tail of the Atlastin
      protein.

PMID- 29661856
TI  - Glutamine-utilizing transaminases are a metabolic vulnerability of TAZ/YAP
      activated cancer cells.
AB  - The transcriptional regulators TAZ and YAP (TAZ/YAP) have emerged as pro
      tumorigenic factors that drive many oncogenic traits, including induction of cell
      growth, resistance to cell death, and activation of processes that promote
      migration and invasion. Here, we report that TAZ/YAP reprogram cellular
      energetics to promote the dependence of breast cancer cell growth on exogenous
      glutamine. Rescue experiments with glutamine-derived metabolites suggest an
      essential role for glutamate and alpha-ketoglutarate (AKG) in TAZ/YAP-driven cell
      growth in the absence of glutamine. Analysis of enzymes that mediate the
      conversion of glutamate to AKG shows that TAZ/YAP induce glutamic-oxaloacetic
      transaminase (GOT1) and phosphoserine aminotransferase (PSAT1) expression and
      that TAZ/YAP activity positively correlates with transaminase expression in
      breast cancer patients. Notably, we find that the transaminase inhibitor
      aminooxyacetate (AOA) represses cell growth in a TAZ/YAP-dependent manner,
      identifying transamination as a potential vulnerable metabolic requirement for
      TAZ/YAP-driven breast cancer.

PMID- 29661857
TI  - Science, politics and ideologies: Global political developments towards
      isolationism, ideology or disregard of facts have scientists concerned about the
      free exchange of ideas and people.

PMID- 29661858
TI  - RNA sensor LGP2 inhibits TRAF ubiquitin ligase to negatively regulate innate
      immune signaling.
AB  - The production of type I interferon (IFN) is essential for cellular barrier
      functions and innate and adaptive antiviral immunity. In response to virus
      infections, RNA receptors RIG-I and MDA5 stimulate a mitochondria-localized
      signaling apparatus that uses TRAF family ubiquitin ligase proteins to activate
      master transcription regulators IRF3 and NFkappaB, driving IFN and antiviral
      target gene expression. Data indicate that a third RNA receptor, LGP2, acts as a
      negative regulator of antiviral signaling by interfering with TRAF family
      proteins. Disruption of LGP2 expression in cells results in earlier and
      overactive transcriptional responses to virus or dsRNA LGP2 associates with the C
      terminus of TRAF2, TRAF3, TRAF5, and TRAF6 and interferes with TRAF ubiquitin
      ligase activity. TRAF interference is independent of LGP2 ATP hydrolysis, RNA
      binding, or its C-terminal domain, and LGP2 can regulate TRAF-mediated signaling
      pathways in trans, including IL-1beta, TNFalpha, and cGAMP These findings provide
      a unique mechanism for LGP2 negative regulation through TRAF suppression and
      extend the potential impact of LGP2 negative regulation beyond the IFN antiviral
      response.

PMID- 29661859
TI  - Mitochondria and the dynamic control of stem cell homeostasis.
AB  - The maintenance of cellular identity requires continuous adaptation to
      environmental changes. This process is particularly critical for stem cells,
      which need to preserve their differentiation potential over time. Among the
      mechanisms responsible for regulating cellular homeostatic responses,
      mitochondria are emerging as key players. Given their dynamic and multifaceted
      role in energy metabolism, redox, and calcium balance, as well as cell death,
      mitochondria appear at the interface between environmental cues and the control
      of epigenetic identity. In this review, we describe how mitochondria have been
      implicated in the processes of acquisition and loss of stemness, with a specific
      focus on pluripotency. Dissecting the biological functions of mitochondria in
      stem cell homeostasis and differentiation will provide essential knowledge to
      understand the dynamics of cell fate modulation, and to establish improved stem
      cell-based medical applications.

PMID- 29661860
TI  - Substrate specificities and efflux efficiencies of RND efflux pumps of
      Acinetobacter baumannii.
AB  - Antibiotic resistant Acinetobacter baumannii causes infections that are extremely
      difficult to treat. A significant role in these resistance profiles is attributed
      to multidrug efflux pumps, especially those belonging to Resistance-Nodulation
      cell Division (RND) superfamily of transporters. In this study, we analyzed
      functions and properties of RND efflux pumps in A. baumannii ATCC 17978. This
      strain is susceptible to antibiotics and does not contain mutations that are
      commonly selected upon exposure to high concentrations of antibiotics. We
      constructed derivatives of ATCC 17978 lacking chromosomally encoded RND pumps and
      complemented these strains by the plasmid-borne genes. We analyzed the substrate
      selectivities and efficiencies of the individual pumps in the context of native
      outer membranes and their hyperporinated variants. Our results show that
      inactivation of AdeIJK provides the strongest potentiation of antibiotic
      activities, whereas inactivation of AdeFGH triggers the overexpression of AdeAB.
      The plasmid-borne overproduction complements the hypersusceptible phenotypes of
      the efflux deletion mutants to the levels of the parental ATCC 17978. Only a few
      antibiotics strongly benefitted from the overproduction of efflux pumps and
      antibacterial activities of some of those depended on the synergistic interaction
      with the low permeability barrier of the outer membrane. Either overproduction or
      inactivation of efflux pumps change dramatically the lipidome of ATCC 17978. We
      conclude that efflux pumps of A. baumannii are tightly integrated into physiology
      of this bacterium and that clinical levels of antibiotic resistance in A.
      baumannii isolates are unlikely to be reached solely due to overproduction of RND
      efflux pumps.Importance RND-type efflux pumps are important contributors in
      development of clinical antibiotic resistance in A. baumannii However, their
      specific roles and the extent of contribution to antibiotic resistance remain
      unclear. We analyzed antibacterial activities of antibiotics in strains with
      different permeability barriers and found that the role of active efflux in
      antibiotic resistance of A. baumannii is limited to a few select antibiotics. Our
      results further show that the impact of efflux pump overproduction on antibiotic
      susceptibility is significantly lower than the previously reported for clinical
      isolates. Additional mechanisms of resistance, in particular those that improve
      the permeability barriers of bacterial cells and act synergistically with active
      efflux pumps are likely involved in antibiotic resistance of clinical A.
      baumannii isolates.

PMID- 29661861
TI  - Forespore Targeting of SpoVD in Bacillus subtilis Is Mediated by the N-Terminal
      Part of the Protein.
AB  - SpoVD and PBP4b are structurally very similar high-molecular-weight, class B
      penicillin-binding proteins produced early during sporulation in Bacillus
      subtilis SpoVD is known to be essential for endospore cortex synthesis and
      thereby the production of heat-resistant spores. The role of PBP4b is still
      enigmatic. Both proteins are synthesized in the cytoplasm of the mother cell.
      PBP4b remains in the cytoplasmic membrane of the mother cell, whereas SpoVD
      accumulates in the forespore outer membrane. By the use of SpoVD/PBP4b chimeras
      with swapped protein domains, we show that the N-terminal part of SpoVD,
      containing the single transmembrane region, determines the forespore targeting of
      the protein.IMPORTANCE Beta-lactam-type antibiotics target penicillin-binding
      proteins (PBPs), which function in cell wall peptidoglycan synthesis. Bacteria of
      a subset of genera, including Bacillus and Clostridium species, can form
      endospores. The extreme resistance of endospores against harsh physicochemical
      conditions is of concern in clinical microbiology and the food industry.
      Endospore cortex layer biogenesis constitutes an experimental model system for
      research on peptidoglycan synthesis. The differentiation of a vegetative
      bacterial cell into an endospore involves the formation of a forespore within the
      cytoplasm of the sporulating cell. A number of proteins, including some PBPs,
      accumulate in the forespore. An understanding of the molecular mechanisms behind
      such subcellular targeting of proteins in bacterial cells can, for example, lead
      to a means of blocking the process of sporulation.

PMID- 29661862
TI  - Increased Isoprenoid Quinone Concentration Modulates Membrane Fluidity in
      Listeria monocytogenes at Low Growth Temperatures.
AB  - Listeria monocytogenes is a food pathogen capable of growing at a broad
      temperature range from 50 degrees C to refrigerator temperatures. A key
      requirement for bacterial activity and growth at low temperatures is the ability
      to adjust the membrane lipid composition to maintain cytoplasmic membrane
      fluidity. In this study, we confirmed earlier findings that the extents of fatty
      acid profile adaptation differed between L. monocytogenes strains. We were able
      to demonstrate for isolates from food that growth rates at low temperatures and
      resistance to freeze-thaw stress were not impaired by a lower adaptive response
      of the fatty acid composition. This indicated the presence of a second adaptation
      mechanism besides temperature-regulated fatty acid synthesis. For strains that
      showed weaker adaptive responses in their fatty acid profiles to low growth
      temperature, we could demonstrate a significantly higher concentration of
      isoprenoid quinones. Three strains even showed a higher quinone concentration
      after growth at 6 degrees C than at 37 degrees C, which is contradictory to the
      reduced respiratory activity at lower growth temperatures. Analyses of the
      membrane fluidity in vivo by measuring generalized polarization and anisotropy
      revealed modulation of the transition phase. Strains with increased quinone
      concentrations showed an expanded membrane transition phase in contrast to
      strains with pronounced adaptations of fatty acid profiles. The correlation
      between quinone concentration and membrane transition phase expansion was
      confirmed by suppression of quinone synthesis. A reduced quinone concentration
      resulted in a narrower transition phase. Expansion of the phase transition zone
      by increasing the concentration of non-fatty acid membrane lipids is discussed as
      an additional mechanism improving adaptation to temperature shifts for L.
      monocytogenes strains.IMPORTANCEListeria monocytogenes is a foodborne pathogen
      with an outstanding temperature range for growth. The ability for growth at
      temperatures close to the freezing point constitutes a serious contamination
      potential for cold stored food. The only known mechanism of the species for
      adaptation of membrane fluidity is modification of the membrane fatty acid
      composition. We were able to demonstrate that, at least for some strains, this
      adaptation mechanism is supported by regulation of the menaquinone concentration.
      The increase of this neutral membrane lipid is correlated with fluidization of
      the membrane under low-temperature conditions and therefore represents a fatty
      acid-independent mechanism for adaptation to low temperatures.

PMID- 29661863
TI  - Vibrio cholerae outer membrane vesicles inhibit bacteriophage infection.
AB  - Novel preventatives could help in efforts to limit Vibrio cholerae infection and
      the spread of cholera. Bacteriophage (or phage) treatment has been proposed to be
      an alternative intervention, given the rapid replication of virulent phages, prey
      specificity, and relative ease of finding new virulent phages. Phage tropism is
      dictated in part by the presence of phage receptors on the bacterial surface.
      While many phages that can kill V. cholerae have been isolated, whether this
      pathogen is able to defend itself by neutralizing phage binding is unknown. Here
      we show that secreted outer membrane vesicles (OMVs) act as a defense mechanism
      that confers protection to V. cholerae against phage predation and that this OMV
      mediated inhibition is phage receptor-dependent. Our results suggest that phage
      therapy or prophylaxis should take into consideration the production of OMVs as a
      bacterial decoy mechanism that could influence the outcome of phage
      treatment.IMPORTANCE Phages have been increasingly realized for the significance
      of their interactions with bacterial cells in multiple environments. Bacteria use
      myriad strategies to defend against phage infection, including: restriction
      modification, abortive infection, phase variation of cell surface receptors,
      phage-inducible chromosomal islands, and CRISPR-Cas systems. The data presented
      here suggest that the apparently passive process of OMV release can also
      contribute to phage defense. By considering the effect of OMVs on infection of V.
      cholerae by three unique virulent phages, ICP1, ICP2 and ICP3, we show that, in
      vitro, a reproducible reduction in bacterial killing is both dose- and phage
      receptor-dependent. This work supports a role for OMVs as natural decoys to
      defend bacteria from phage predation.

PMID- 29661864
TI  - Source of the Fitness Defect in Rifamycin-Resistant Mycobacterium tuberculosis
      RNA Polymerase and the Mechanism of Compensation by Mutations in the beta'
      Subunit.
AB  - Mycobacterium tuberculosis is a critical threat to human health due to the
      increased prevalence of rifampin resistance (RMPr). Fitness defects have been
      observed in RMPr mutants with amino acid substitutions in the beta subunit of RNA
      polymerase (RNAP). In clinical isolates, this fitness defect can be ameliorated
      by the presence of secondary mutations in the double-psi beta-barrel (DPBB)
      domain of the beta' subunit of RNAP. To identify factors contributing to the
      fitness defects observed in vivo, several in vitro RNA transcription assays were
      utilized to probe initiation, elongation, termination, and 3'-RNA hydrolysis with
      the wild-type and RMPrM. tuberculosis RNAPs. We found that the less prevalent
      RMPr mutants exhibit significantly poorer termination efficiencies relative to
      the wild type, an important factor for proper gene expression. We also found that
      several mechanistic aspects of transcription of the RMPr mutant RNAPs are
      impacted relative to the wild type. For the clinically most prevalent mutant, the
      betaS450L mutant, these defects are mitigated by the presence of
      secondary/compensatory mutations in the DPBB domain of the beta' subunit.

PMID- 29661865
TI  - Modeling and Simulation of Pretomanid Pharmacokinetics in Pulmonary Tuberculosis
      Patients.
AB  - Pretomanid is a nitroimidazole antibiotic in late-phase clinical testing as a
      component of several novel antituberculosis (anti-TB) regimens. A population
      pharmacokinetic model for pretomanid was constructed using a Bayesian analysis of
      data from two phase 2 studies, PA-824-CL-007 and PA-824-CL-010, conducted with
      adult (median age, 27 years) patients in Cape Town, South Africa, with newly
      diagnosed pulmonary TB. Combined, these studies included 63 males and 59 females
      administered once-daily oral pretomanid doses of 50, 100, 150, 200, 600, 1,000,
      or 1,200 mg for 14 days. The observed pretomanid plasma concentration-time
      profiles for all tested doses were described by a one-compartment model with
      first-order absorption and elimination and a sigmoidal bioavailability dependent
      on dose, time, and the predose fed state. Allometric scaling with body weight
      (normalized to 70 kg) was used for volume of distribution and clearance, with the
      scaling exponents equal to 1 and 3/4, respectively. The posterior population
      geometric means for the clearance and volume of distribution allometric constants
      were 4.8 +/- 0.2 liters/h and 130 +/- 5 liters, respectively, and the posterior
      population geometric mean for the half-maximum-effect dose for the reduction of
      bioavailability was 450 +/- 50 mg. Interindividual variability, described by the
      percent coefficient of variation, was 32% +/- 3% for clearance, 17% +/- 4% for
      the volume of distribution, and 74% +/- 9% for the half-maximum-effect dose. This
      model provides a dose-exposure relationship for pretomanid in adult TB patients
      with potential applications to dose selection in individuals and to further
      clinical testing of novel pretomanid-containing anti-TB regimens.

PMID- 29661866
TI  - Reciprocal Effects of Antiretroviral Drugs Used To Treat HIV Infection on the
      Fibroblast Growth Factor 21/beta-Klotho System.
AB  - Following antiretroviral therapy, HIV-infected patients show increased
      circulating levels of the antidiabetic hormone fibroblast growth factor 21
      (FGF21). In contrast, the expression of the FGF21-obligatory coreceptor beta
      Klotho (KLB) is reduced in target tissues. This situation is comparable to the
      FGF21 resistance status observed in obesity and type 2 diabetes. Here, we
      performed the first systematic study of the effects of distinct members of
      different antiretroviral drug classes on the FGF21/KLB system in human hepatic,
      adipose, and skeletal muscle cells. Most protease inhibitors and the
      nonnucleoside reverse transcriptase inhibitor efavirenz induced FGF21 gene
      expression. Neither nucleoside reverse transcriptase inhibitors nor the viral
      entry inhibitor maraviroc had any effect. Among the integrase inhibitors,
      elvitegravir significantly induced FGF21 expression, whereas raltegravir had
      minor effects only in adipose cells. In human hepatocytes and adipocytes, known
      target cells of FGF21 action, efavirenz, elvitegravir, and the lopinavir
      ritonavir combination exerted inhibitory effects on KLB gene expression. Drug
      treatments that elicited FGF21 induction/KLB repression were those found to
      induce endoplasmic reticulum (ER) stress and oxidative stress. Notably, the
      pharmacological agents thapsigargin and tunicamycin, which induce these stress
      pathways, mimicked the effects of drug treatments. Moreover, pharmacological
      inhibitors of either ER or oxidative stress significantly impaired lopinavir
      ritonavir-induced regulation of FGF21, but not KLB. In conclusion, the present in
      vitro screen study identifies the antiretroviral drugs that affect FGF21/KLB
      expression in human cells. The present results could have important implications
      for the management of comorbidities resulting from side effects of specific
      antiretroviral drugs for the treatment of HIV-infected patients.

PMID- 29661867
TI  - Triclosan Is an Aminoglycoside Adjuvant for Eradication of Pseudomonas aeruginosa
      Biofilms.
AB  - One of the most important clinical obstacles in cystic fibrosis (CF) treatment is
      antibiotic treatment failure due to biofilms produced by Pseudomonas aeruginosa
      The ability of this pathogen to survive eradication by tobramycin and pathoadapt
      into a hyperbiofilm state leading to chronic infections is key to its success.
      Retrospective studies have demonstrated that preventing this pathoadaptation by
      improving eradication is essential to extend the lives of CF patients. To
      identify adjuvants that enhance tobramycin eradication of P. aeruginosa, we
      performed a high-throughput screen of 6,080 compounds from four drug-repurposing
      libraries. We identified that the Food and Drug Administration (FDA)-approved
      compound triclosan, in combination with tobramycin, resulted in a 100-fold
      reduction of viable cells within biofilms at 6 h, but neither compound alone had
      significant antimicrobial activity against biofilms. This synergistic treatment
      significantly accelerated the killing of biofilms compared to that with
      tobramycin treatment alone, and the combination was effective against 6/7 CF
      clinical isolates compared to tobramycin treatment alone, including a tobramycin
      resistant strain. Further, triclosan and tobramycin killed persister cells,
      causing a 100-fold reduction by 8 h and complete eradication by 24 h. Triclosan
      also enhances tobramycin killing of multiple Burkholderia cenocepacia and
      Staphylococcus aureus clinical isolates grown as biofilms. Additionally,
      triclosan showed synergy with other aminoglycosides, such as gentamicin or
      streptomycin. Triclosan is a well-tolerated aminoglycoside adjuvant shown to be
      safe for human use that could improve the treatment of biofilm-based infections.

PMID- 29661868
TI  - Spread of Clonally Related Escherichia coli Strains Harboring an IncA/C1 Plasmid
      Encoding IMP-8 and Its Recruitment into an Unrelated MCR-1-Containing Isolate.
AB  - Ten IMP-8-producing Escherichia coli isolates were recovered from surveillance
      cultures of a neonatal intensive care unit; eight of the isolates were clonally
      related. A 168.2-kb blaIMP-8 plasmid was fully sequenced, and it corresponded to
      the recently described IncA/C1-ST13 plasmid. This plasmid was detected in all
      isolates, even in those that were not clonally related. One unrelated isolate was
      also resistant to colistin and positive for mcr-1 This marker was located in a
      62.7-kb IncI2 plasmid, which was also fully sequenced.

PMID- 29661869
TI  - Moxifloxacin Replacement in Contemporary Tuberculosis Drug Regimens Is
      Ineffective against Persistent Mycobacterium tuberculosis in the Cornell Mouse
      Model.
AB  - Tuberculosis (TB), which is caused by Mycobacterium tuberculosis, remains a
      leading killer worldwide, and disease control is hampered by the ineffective
      control of persistent infections. Substitution of moxifloxacin for isoniazid or
      ethambutol in standard anti-TB regimens reduces the treatment duration and
      relapse rates in animal studies, and 4-month regimens were not noninferior in
      clinical trials. Resuscitation-promoting factor (RPF)-dependent bacilli have
      recently been implicated in M. tuberculosis persistence. We aimed to investigate
      the therapeutic effects of the substitution of moxifloxacin for a drug used in
      the standard drug regimen in eradicating CFU count-positive and RPF-dependent
      persistent M. tuberculosis using the Cornell murine model. M. tuberculosis
      infected mice were treated with regimens in which either isoniazid or ethambutol
      was replaced by moxifloxacin in the standard regimen. The efficacy of the
      regimens for bacterial CFU count elimination and removal of persistent tubercle
      bacilli, evaluated using culture filtrate (CF) derived from M. tuberculosis
      strain H37Rv, was compared to that of the standard regimen. We also measured
      disease relapse rates. The regimen in which moxifloxacin replaced isoniazid
      achieved total organ CFU count clearance at 11 weeks posttreatment, which was
      faster than that by the standard regimen (14 weeks), and showed a 34% lower
      relapse rate. The regimen in which moxifloxacin replaced ethambutol was similar
      to standard regimens in these regards. Importantly, neither the regimen in which
      moxifloxacin replaced isoniazid or ethambutol nor the standard regimen could
      remove CF-dependent persistent bacilli. The finding of CF-dependent persistent M.
      tuberculosis in TB treatment requires confirmation in human studies and has
      implications for future drug design, testing, and clinical applications.

PMID- 29661870
TI  - Amikacin Inhalation as Salvage Therapy for Refractory Nontuberculous
      Mycobacterial Lung Disease.
AB  - Although guidelines recommend amikacin (AMK) inhalation therapy for difficult-to
      treat nontuberculous mycobacterial lung disease (NTM-LD), data are limited
      regarding the safety and clinical efficacy of this salvage therapy. We
      retrospectively evaluated the treatment outcomes of 77 patients with refractory
      NTM-LD caused by Mycobacterium abscessus complex (MABC) or M. avium complex (MAC)
      who initiated AMK inhalation therapy between February 2015 and June 2016. MABC
      was the most common etiology (n = 48, 62%), followed by MAC (n = 20, 26%) and
      mixed infections (n = 9, 12%). Isolates with macrolide resistance and baseline
      AMK resistance were identified in 63 (82%) patients and 5 (6%) patients,
      respectively. At 12 months after AMK inhalation therapy, 49% of patients had
      symptomatic improvement, whereas 42% had radiological improvement. Conversion to
      a negative sputum culture occurred in 14 (18%) patients, and the culture
      conversion rate was higher in patients infected with macrolide-susceptible
      isolates (7/14, 50%) than in those infected with macrolide-resistant isolates
      (7/63, 11%) (P = 0.003). Significant decreases in sputum semiquantitative culture
      positivity occurred after AMK inhalation therapy (P < 0.001). On multivariate
      analysis, conversion to a negative sputum culture was associated with mixed
      infections (P = 0.009), a forced expiratory volume in 1 s of greater than 60% (P
      = 0.008), and the absence of macrolide resistance (P = 0.003). Thirty-eight
      percent of patients experienced adverse effects, with ototoxicity (n = 15) being
      the most common. AMK inhalation salvage therapy may improve the treatment
      responses in some patients with refractory NTM-LD. However, considering the
      common adverse effects, further evaluation of the optimal dosage and intervals
      for AMK inhalation therapy is needed.

PMID- 29661871
TI  - The Genetic Polymorphism UGT1A4*3 Is Associated with Low Posaconazole Plasma
      Concentrations in Hematological Malignancy Patients Receiving the Oral
      Suspension.
AB  - The metabolism of posaconazole is mediated mainly by uridine 5'-diphospho
      glucuronosyltransferase (UGT) enzymes, especially UGT1A4. The aim of this study
      was to investigate the effects of genetic polymorphisms on the posaconazole
      plasma concentration (PPC). This prospective study was conducted from September
      2014 to August 2016. We enrolled patients with acute myeloid leukemia or
      myelodysplastic syndrome treated with posaconazole oral suspension (200 mg) three
      times daily for fungal prophylaxis. The patients were examined for the multidrug
      resistance gene 1 3435C>T and 2677G>T/A variations and the UGT1A4*3 allele by
      direct sequencing of DNA from peripheral whole-blood samples. We defined poor
      absorbers to be those with PPCs of <200 ng/ml and the optimal PPC to be >=700
      ng/ml on day 8. The associations between genetic polymorphisms and the PPC were
      evaluated using multivariate logistic regression analysis including clinical
      variables. During the study period, 132 patients were enrolled. Six patients
      (4.5%) were defined as poor absorbers, and 49 patients (37.1%) did not reach the
      optimal PPC on day 8. In multivariate analysis, the independent risk factors for
      a poor absorber were at least one UGT1A4*3 allele (adjusted odds ratio [aOR],
      18.81; 95% confidence interval [CI], 1.09 to 324.44; P = 0.043) and poor oral
      food intake (aOR per -100 kcal, 1.44; 95% CI, 1.04 to 1.99; P = 0.029). There was
      no statistically significant association between the genetic polymorphisms and
      achievement of the optimal PPC on day 8. The UGT1A4*3 polymorphism is an
      independent risk factor for being a poor absorber of posaconazole oral suspension
      in patients with hematological malignancies.

PMID- 29661872
TI  - Treating Anthrax-Induced Meningitis in Rabbits.
AB  - Treatment of anthrax is challenging, especially during the advanced stages of the
      disease. Recently, the Centers for Disease Control and Prevention (CDC) updated
      its recommendations for postexposure prophylaxis and treatment of exposed
      populations (before and after symptom onset). These recommendations
      distinguished, for the first time, between systemic disease with and without
      meningitis, a common and serious complication of anthrax. The CDC considers all
      systemic cases meningeal unless positively proven otherwise. The treatment of
      patients suffering from systemic anthrax with suspected or confirmed meningitis
      includes the combination of three antibiotics, i.e., a fluoroquinolone
      (levofloxacin or ciprofloxacin), a beta-lactam (meropenem or imipenem), and a
      protein synthesis inhibitor (linezolid or clindamycin). In addition, treatment
      with an antitoxin (anti-protective antigen antibodies) and dexamethasone should
      be applied. Since the efficacy of most of these treatments has not been
      demonstrated, especially in animal meningitis models, we developed an anthrax
      meningitis model in rabbits and tested several of these recommendations. We
      demonstrated that, in this model, ciprofloxacin, linezolid, and meropenem were
      ineffective as single treatments, while clindamycin was highly effective.
      Furthermore, combined treatments of ciprofloxacin and linezolid or ciprofloxacin
      and dexamethasone failed in treating rabbits with meningitis. We demonstrated
      that dexamethasone actually hindered blood-brain barrier penetration by
      antibiotics, reducing the effectiveness of antibiotic treatment of anthrax
      meningitis in this rabbit model.

PMID- 29661873
TI  - Characterizing Blood-Stage Antimalarial Drug MIC Values In Vivo Using Reinfection
      Patterns.
AB  - The MIC is an essential quantitative measure of the asexual blood-stage effect of
      an antimalarial drug. In areas of high malaria transmission, and thus frequent
      individual infection, patients who are treated with slowly eliminated
      antimalarials become reinfected as drug concentrations decline. In the frequent
      relapse forms of Plasmodium vivax and in Plasmodium ovale malaria, recurrent
      infection occurs from relapses which begin to emerge from the liver approximately
      2 weeks after the primary illness. An important determinant of the interval from
      starting treatment of a symptomatic infection to the patency of these recurrent
      infections is the in vivo concentration-response relationship and thus the in
      vivo MIC. Using mechanistic knowledge of parasite asexual replication and the
      pharmacokinetic and pharmacodynamic properties of the antimalarial drugs, a
      generative statistical model was derived which relates the concentration-response
      relationship to time of reinfection patency. This model was used to estimate the
      in vivo MIC of chloroquine in the treatment of Plasmodium vivax malaria.

PMID- 29661874
TI  - Characterization of Extensively Drug-Resistant or Pandrug-Resistant Sequence Type
      147 and 101 OXA-48-Producing Klebsiella pneumoniae Causing Bloodstream Infections
      in Patients in an Intensive Care Unit.
AB  - Carbapenem-resistant Klebsiella pneumoniae causes important health care
      associated infections worldwide. An outbreak of sequence type 11 (ST11) OXA-48
      producing K. pneumoniae (OXA-48-Kp) isolates occurred in Tzaneio Hospital in 2012
      and was contained until 2014, when OXA-48-Kp reemerged. The present study
      involved 19 bloodstream infection (BSI) OXA-48-Kp isolates recovered from 19
      intensive care unit (ICU) patients hospitalized between August 2014 and July
      2016. MICs were determined by broth microdilution. Beta-lactamase genes were
      detected by PCR. All isolates were typed by pulsed-field gel
      electrophoresis/multilocus sequence typing (PFGE/MLST), and 10 representative
      isolates were typed by next-generation sequencing (NGS). Of the 19 study
      patients, 9 had previous hospitalizations, and 10 carried OXA-48-Kp prior to BSI
      isolation; median time from ICU admission to BSI was 29 days. Four OXA-48-Kp
      isolates belonged to PFGE profile A (ST147) and were pandrug resistant (PDR),
      while 15 isolates exhibited PFGE profile B (ST101) and were extensively drug
      resistant. Genes detected via NGS resistome analysis accounted for most of the
      resistance phenotypes, except for tigecycline and fosfomycin. Insertional
      inactivation of mgrB (distinct per clone) conferred colistin resistance in all 19
      isolates. NGS single nucleotide polymorphism (SNP) analysis validated the clonal
      relatedness of the ST147 and ST101 strains and revealed the possible presence of
      two index ST147 strains and the microevolution of ST101 strains. Distinct, but
      highly related, IncL OXA-48-encoding plasmid lineages were identified; plasmids
      of the ST147 strains were identical with the plasmid of ST11 OXA-48-Kp which
      caused the 2012 outbreak. In conclusion, biclonal circulation of OXA-48-Kp and,
      alarmingly, emergence of a PDR clone are reported. These observations, along with
      the challenging phenotypic detection of OXA-48 producers and the high reported
      transmissibility of blaOXA-48, necessitate intensive efforts to prevent their
      further spread.

PMID- 29661875
TI  - HC2091 Kills Mycobacterium tuberculosis by Targeting the MmpL3 Mycolic Acid
      Transporter.
AB  - Tuberculosis, caused by the intracellular pathogen Mycobacterium tuberculosis, is
      a deadly disease that requires a long course of treatment. The emergence of drug
      resistant strains has driven efforts to discover new small molecules that can
      kill the bacterium. Here, we report characterizations of the compound HC2091,
      which kills M. tuberculosis in a time- and dose-dependent manner in vitro and
      inhibits M. tuberculosis growth in macrophages. Whole-genome sequencing of
      spontaneous HC2091-resistant mutants identified single-nucleotide variants in the
      mmpL3 mycolic acid transporter gene. HC2091-resistant mutants do not exhibit
      cross-resistance with the well-characterized Mycobacterium membrane protein large
      3 (MmpL3) inhibitor SQ109, suggesting a distinct mechanism of interaction with
      MmpL3. Additionally, HC2091 does not modulate bacterial membrane potential or
      kill nonreplicating M. tuberculosis, thus acting differently from other known
      MmpL3 inhibitors. RNA sequencing (RNA-seq) transcriptional profiling and lipid
      profiling of M. tuberculosis treated with HC2091 or SQ109 show that the two
      compounds target a similar pathway. HC2091 has a chemical structure dissimilar to
      those of previously described MmpL3 inhibitors, supporting the notion that HC2091
      is a new class of MmpL3 inhibitor.

PMID- 29661876
TI  - Antimicrobial and Antibiofilm Efficacy of Graphene Oxide against Chronic Wound
      Microorganisms.
AB  - Chronic wounds represent an increasing problem worldwide. Graphene oxide (GO) has
      been reported to exhibit strong antibacterial activity toward both Gram-positive
      and Gram-negative bacteria. The aim of this work was to investigate the in vitro
      antimicrobial and antibiofilm efficacy of GO against wound pathogens.
      Staphylococcus aureus PECHA 10, Pseudomonas aeruginosa PECHA 4, and Candida
      albicans X3 clinical isolates were incubated with 50 mg/liter of GO for 2 and 24
      h to evaluate the antimicrobial effect. Optical and atomic force microscopy
      images were performed to visualize the effect of GO on microbial cells. Moreover,
      the antibiofilm effect of GO was tested on biofilms, both in formation and
      mature. Compared to the respective time controls, GO significantly reduced the S.
      aureus growth both at 2 and 24 h in a time-dependent way, and it displayed a
      bacteriostatic effect in respect to the GO t = 0; an immediate (after 2 h)
      slowdown of bacterial growth was detected for P. aeruginosa, whereas a tardive
      effect (after 24 h) was recorded for C. albicans Atomic force microscopy images
      showed the complete wrapping of S. aureus and C. albicans with GO sheets, which
      explains its antimicrobial activity. Moreover, significant inhibition of biofilm
      formation and a reduction of mature biofilm were recorded for each detected
      microorganism. The antibacterial and antibiofilm properties of GO against chronic
      wound microorganisms make it an interesting candidate to incorporate into wound
      bandages to treat and/or prevent microbial infections.

PMID- 29661877
TI  - Therapeutic Efficacy of Bumped Kinase Inhibitor 1369 in a Pig Model of Acute
      Diarrhea Caused by Cryptosporidium hominis.
AB  - Recent reports highlighting the global significance of cryptosporidiosis among
      children have renewed efforts to develop control measures. We evaluated the
      efficacy of bumped kinase inhibitor (BKI) 1369 in the gnotobiotic piglet model of
      acute diarrhea caused by Cryptosporidium hominis, the species responsible for
      most human cases. Five-day treatment with BKI 1369 reduced signs of disease early
      during treatment compared to those of untreated animals. Piglets treated with BKI
      1369 exhibited significant reductions of oocyst excretion, mucosal colonization
      by C. hominis, and mucosal lesions, which resulted in considerable symptomatic
      improvement. BKI 1369 reduced the parasite burden and disease severity in the
      gnotobiotic pig model. Together these data suggest that a BKI-mediated
      therapeutic may be an effective treatment against cryptosporidiosis.

PMID- 29661878
TI  - Plasticity of Aminoglycoside Binding to Antibiotic Kinase APH(2")-Ia.
AB  - The APH(2")-Ia aminoglycoside resistance enzyme forms the C-terminal domain of
      the bifunctional AAC(6')-Ie/APH(2")-Ia enzyme and confers high-level resistance
      to natural 4,6-disubstituted aminoglycosides. In addition, reports have suggested
      that the enzyme can phosphorylate 4,5-disubstituted compounds and aminoglycosides
      with substitutions at the N1 position. Previously determined structures of the
      enzyme with bound aminoglycosides have not indicated how these noncanonical
      substrates may bind and be modified by the enzyme. We carried out
      crystallographic studies to directly observe the interactions of these compounds
      with the aminoglycoside binding site and to probe the means by which these
      noncanonical substrates interact with the enzyme. We find that APH(2")-Ia
      maintains a preferred mode of binding aminoglycosides by using the conserved
      neamine rings when possible, with flexibility that allows it to accommodate
      additional rings. However, if this binding mode is made impossible because of
      additional substitutions to the standard 4,5- or 4,6-disubstituted aminoglycoside
      architecture, as in lividomycin A or the N1-substituted aminoglycosides, it is
      still possible for these aminoglycosides to bind to the antibiotic binding site
      by using alternate binding modes, which explains the low rates of noncanonical
      phosphorylation activities seen in enzyme assays. Furthermore, structural studies
      of a clinically observed arbekacin-resistant mutant of APH(2")-Ia revealed an
      altered aminoglycoside binding site that can stabilize an alternative binding
      mode for N1-substituted aminoglycosides. This mutation may alter and expand the
      aminoglycoside resistance spectrum of the wild-type enzyme in response to newly
      developed aminoglycosides.

PMID- 29661880
TI  - Refractory Hypokalemia from Syndrome of Apparent Mineralocorticoid Excess on Low
      Dose Posaconazole.

PMID- 29661879
TI  - Accelerating Early Antituberculosis Drug Discovery by Creating Mycobacterial
      Indicator Strains That Predict Mode of Action.
AB  - Due to the rise of drug-resistant forms of tuberculosis, there is an urgent need
      for novel antibiotics to effectively combat these cases and shorten treatment
      regimens. Recently, drug screens using whole-cell analyses have been shown to be
      successful. However, current high-throughput screens focus mostly on stricto
      sensu life/death screening that give little qualitative information. In doing so,
      promising compound scaffolds or nonoptimized compounds that fail to reach
      inhibitory concentrations are missed. To accelerate early tuberculosis (TB) drug
      discovery, we performed RNA sequencing on Mycobacterium tuberculosis and
      Mycobacterium marinum to map the stress responses that follow upon exposure to
      subinhibitory concentrations of antibiotics with known targets, ciprofloxacin,
      ethambutol, isoniazid, streptomycin, and rifampin. The resulting data set
      comprises the first overview of transcriptional stress responses of mycobacteria
      to different antibiotics. We show that antibiotics can be distinguished based on
      their specific transcriptional stress fingerprint. Notably, this fingerprint was
      more distinctive in M. marinum We decided to use this to our advantage and
      continue with this model organism. A selection of diverse antibiotic stress genes
      was used to construct stress reporters. In total, three functional reporters were
      constructed to respond to DNA damage, cell wall damage, and ribosomal inhibition.
      Subsequently, these reporter strains were used to screen a small anti-TB compound
      library to predict the mode of action. In doing so, we identified the putative
      modes of action for three novel compounds, which confirms the utility of our
      approach.

PMID- 29661881
TI  - Genetic Diversity among Staphylococcus aureus Isolates Showing Oxacillin and/or
      Cefoxitin Resistance Not Linked to the Presence of mec Genes.
AB  - Methicillin-resistant Staphylococcus aureus isolates lacking mec genes (n = 32),
      collected from Belgian hospitals, were characterized for their beta-lactamase
      production and the presence of mutations in pbp genes, the pbp4 promoter, and
      genes involved in penicillin-binding protein 4 overproduction (gdpP and yjbH).
      Twelve isolates were beta-lactamase hyperproducers (BHPs), while 12 non-BHP
      isolates might produce an incomplete GdpP protein. Most isolates showed
      nucleotide missense mutations in pbp genes. A few isolates also showed mutations
      in the pbp4 promoter.

PMID- 29661882
TI  - In Vitro Antimicrobial Susceptibility of Clinical Isolates of Borrelia miyamotoi.
AB  - Borrelia miyamotoi is an emerging relapsing fever (RF) Borrelia species that is
      reported to cause human disease in regions in which Lyme borreliosis is endemic.
      We recently showed that B. miyamotoi tick isolates are resistant to amoxicillin
      in vitro; however, clinical isolates have not been studied. Therefore, our aim
      was to show the antimicrobial susceptibility of recently obtained clinical
      isolates of B. miyamotoi A dilution series of various antibiotics was made in
      modified Kelly-Pettenkofer medium with 10% fetal calf serum. The susceptibilities
      of different B. miyamotoi clinical, B. miyamotoi tick, RF Borrelia, and Borrelia
      burgdorferisensu lato isolates were tested by measuring MICs through colorimetric
      changes and by counting motile spirochetes by dark-field microscopy after 72 h of
      incubation. The ceftriaxone and azithromycin MIC ranges of the six B. miyamotoi
      clinical isolates tested were 0.03 to 0.06 mg/liter and 0.0016 to 0.0032
      mg/liter, respectively. These values are similar to MICs for RF Borrelia strains
      and B. miyamotoi tick isolates. All tested RF Borrelia strains were susceptible
      to doxycycline (microscopic MIC range, 0.0625 to 0.25 mg/liter). In contrast to
      the MICs of the tested B. burgdorferi sensu lato strains and in line with our
      previous findings, the amoxicillin MICs (range, 8 to 32 mg/liter) of all RF
      Borrelia strains, including B. miyamotoi clinical isolates, were above the
      clinical breakpoint for resistance (<=4 mg/liter). Clinical isolates of B.
      miyamotoi are highly susceptible to doxycycline, azithromycin, and ceftriaxone in
      vitro Interestingly, as described previously for tick isolates, amoxicillin shows
      poor in vitro activity against B. miyamotoi clinical isolates.

PMID- 29661883
TI  - Unexpected Replication Boost by Simeprevir for Simeprevir-Resistant Variants in
      Genotype 1a Hepatitis C Virus.
AB  - Simeprevir is a novel NS3/4A protease inhibitor (PI) of hepatitis C virus (HCV).
      The baseline polymorphism NS3-Q80K is frequently observed in genotype (GT) 1a HCV
      and often associated with treatment failure in simeprevir-containing regimens. We
      aimed to elucidate mechanisms of treatment failure due to NS3-Q80K. We included a
      Q80R mutation in our study and generated a series of Huh-7.5 cell lines, each of
      which harbored either wild-type GT 1a strain H77S.3 or the Q80K or Q80R variant.
      The cells were cultured with increasing concentrations of simeprevir, and NS3
      domain sequences were determined. The mutations identified by sequence analyses
      were subsequently introduced into H77S.3. The sensitivity of each mutant to the
      NS3/4A PIs simeprevir, asunaprevir, grazoprevir, and paritaprevir was analyzed.
      We introduced the mutations into GT 1b strain N.2 and compared the sensitivity to
      simeprevir with that of GT 1a strain H77S.3. While simeprevir treatment selected
      mutations at residue D168, such as D168A/V in the wild-type virus, an additional
      mutation at residue R155, R155K, was selected in Q80K/R variants at simeprevir
      concentrations of <2.5 MUM. Sensitivity analyses showed that simeprevir
      concentrations of <1 MUM significantly boosted the replication of Q80K/R R155K
      variants. Interestingly, this boost was not observed with the other NS3/4A PIs or
      in Q80R R155Q/G/T/W variants or GT 1b isolates. The boosted replication of the
      Q80K+R155K variant by simeprevir could be related to treatment failure in
      simeprevir-containing antiviral treatments in GT 1a HCV-infected patients with
      the NS3-Q80K polymorphism. This result provides new insight into how resistance
      associated variants can cause treatment failure.

PMID- 29661884
TI  - Molecular Characterization of qnrVC Genes and Their Novel Alleles in Vibrio spp.
      Isolated from Food Products in China.
AB  - This study reports the prevalences of qnrVC genes in 74 ciprofloxacin-resistant
      Vibrio sp. isolates. Two novel functional qnrVC alleles, qnrVC8 and qnrVC9,
      sharing 98% and 99% nucleotide similarity with qnrVC6 and qnrVC7, respectively,
      were identified. Our findings suggested that carriage of qnrVC alleles, together
      with target mutations in gyrA and parC genes, may contribute to the development
      of fluoroquinolone resistance in Vibrio species, posing a serious threat to
      public health.

PMID- 29661888
TI  - What's happening in Neurology(r).

PMID- 29661887
TI  - In search of a putative imaging biomarker for Fabry disease: Go with the flow?

PMID- 29661885
TI  - The long non-coding RNA Paupar promotes KAP1-dependent chromatin changes and
      regulates olfactory bulb neurogenesis.
AB  - Many long non-coding RNAs (lncRNAs) are expressed during central nervous system
      (CNS) development, yet their in vivo roles and mechanisms of action remain poorly
      understood. Paupar, a CNS-expressed lncRNA, controls neuroblastoma cell growth by
      binding and modulating the activity of transcriptional regulatory elements in a
      genome-wide manner. We show here that the Paupar lncRNA directly binds KAP1, an
      essential epigenetic regulatory protein, and thereby regulates the expression of
      shared target genes important for proliferation and neuronal differentiation.
      Paupar promotes KAP1 chromatin occupancy and H3K9me3 deposition at a subset of
      distal targets, through the formation of a ribonucleoprotein complex containing
      Paupar, KAP1 and the PAX6 transcription factor. Paupar-KAP1 genome-wide co
      occupancy reveals a fourfold enrichment of overlap between Paupar and KAP1 bound
      sequences, the majority of which also appear to associate with PAX6. Furthermore,
      both Paupar and Kap1 loss-of-function in vivo disrupt olfactory bulb
      neurogenesis. These observations provide important conceptual insights into the
      trans-acting modes of lncRNA-mediated epigenetic regulation and the mechanisms of
      KAP1 genomic recruitment, and identify Paupar and Kap1 as regulators of
      neurogenesis in vivo.

PMID- 29661889
TI  - What's happening in Neurology(r)Clinical Practice.

PMID- 29661886
TI  - Distinct in vivo roles of secreted APP ectodomain variants APPsalpha and APPsbeta
      in regulation of spine density, synaptic plasticity, and cognition.
AB  - Increasing evidence suggests that synaptic functions of the amyloid precursor
      protein (APP), which is key to Alzheimer pathogenesis, may be carried out by its
      secreted ectodomain (APPs). The specific roles of APPsalpha and APPsbeta
      fragments, generated by non-amyloidogenic or amyloidogenic APP processing,
      respectively, remain however unclear. Here, we expressed APPsalpha or APPsbeta in
      the adult brain of conditional double knockout mice (cDKO) lacking APP and the
      related APLP2. APPsalpha efficiently rescued deficits in spine density, synaptic
      plasticity (LTP and PPF), and spatial reference memory of cDKO mice. In contrast,
      APPsbeta failed to show any detectable effects on synaptic plasticity and spine
      density. The C-terminal 16 amino acids of APPsalpha (lacking in APPsbeta) proved
      sufficient to facilitate LTP in a mechanism that depends on functional nicotinic
      alpha7-nAChRs. Further, APPsalpha showed high-affinity, allosteric potentiation
      of heterologously expressed alpha7-nAChRs in oocytes. Collectively, we identified
      alpha7-nAChRs as a crucial physiological receptor specific for APPsalpha and show
      distinct in vivo roles for APPsalpha versus APPsbeta. This implies that reduced
      levels of APPsalpha that might occur during Alzheimer pathogenesis cannot be
      compensated by APPsbeta.

PMID- 29661890
TI  - What's happening in Neurology(r)Genetics.

PMID- 29661891
TI  - What's happening in Neurology(r)Neuroimmunology & Neuroinflammation.

PMID- 29661892
TI  - Metabolic coupling of axons and glial cells: Implications for multiple sclerosis
      progression.

PMID- 29661893
TI  - Video NeuroImages: Head titubation in anti-mGluR1 autoantibody-associated
      cerebellitis.

PMID- 29661894
TI  - Clinical Reasoning: A 56-year-old woman with acute vertigo and diplopia.

PMID- 29661895
TI  - Editors' note: Teaching Video NeuroImages: Olivary enlargement and pharyngeal
      nystagmus.

PMID- 29661896
TI  - Reader response: Teaching Video NeuroImages: Olivary enlargement and pharyngeal
      nystagmus.

PMID- 29661897
TI  - Reader response: Teaching Video NeuroImages: Olivary enlargement and pharyngeal
      nystagmus.

PMID- 29661899
TI  - Alemtuzumab CARE-MS I 5-year follow-up: Durable efficacy in the absence of
      continuous MS therapy.

PMID- 29661898
TI  - Author response: Teaching Video NeuroImages: Olivary enlargement and pharyngeal
      nystagmus.

PMID- 29661900
TI  - Increased resting cerebral blood flow in adult Fabry disease: MRI arterial spin
      labeling study.
AB  - OBJECTIVE: To assess resting cerebral blood flow (CBF) in the whole-brain and
      cerebral white matter (WM) and gray matter (GM) of adults with Fabry disease
      (FD), using arterial spin labeling (ASL) MRI, and to investigate CBF correlations
      with WM hyperintensity (WMH) volume and the circulating biomarker lyso-Gb3.
      METHODS: This cross-sectional, case-control study included 25 patients with
      genetically confirmed FD and 18 age-matched healthy controls. We quantified
      resting CBF using Quantitative Signal Targeting With Alternating Radiofrequency
      Labeling of Arterial Regions (QUASAR) ASL MRI. We measured WMH volume using
      semiautomated software. We measured CBF in regions of interest in whole-brain,
      WM, and deep GM, and assessed correlations with WMH volume and plasma lyso-Gb3.
      RESULTS: The mean age (% male) for FD and healthy controls was 42.2 years (44%)
      and 37.1 years (50%). Mean whole-brain CBF was 27.56 mL/100 mL/min (95%
      confidence interval [CI] 23.78-31.34) for FD vs 22.39 mL/100 mL/min (95% CI 20.08
      24.70) for healthy controls, p = 0.03. In WM, CBF was higher in FD (22.42 mL/100
      mL/min [95% CI 17.72-27.12] vs 16.25 mL/100 mL/min [95% CI 14.03-18.48], p =
      0.05). In deep GM, CBF was similar between groups (40.41 mL/100 mL/min [95% CI
      36.85-43.97] for FD vs 37.46 mL/100 mL/min [95% CI 32.57-42.35], p = 0.38). In
      patients with FD with WMH (n = 20), whole-brain CBF correlated with WMH volume (r
      = 0.59, p = 0.006), not with plasma lyso-Gb3. CONCLUSION: In FD, resting CBF is
      increased in WM but not deep GM. In FD, CBF correlates with WMH, suggesting that
      cerebral perfusion changes might contribute to, or result from, WM injury.

PMID- 29661903
TI  - Body mass index, sitting time, and risk of Parkinson disease.
AB  - OBJECTIVE: Causes of Parkinson disease are largely unknown, but recent evidence
      suggests associations with physical activity and anthropometric measures.
      METHODS: We prospectively analyzed a cohort of 41,638 Swedish men and women by
      detailed assessment of lifestyle factors at baseline in 1997. Complete follow-up
      until 2010 was achieved through linkage to population-based registers. We used
      multivariable Cox proportional hazards models to estimate hazard ratios with 95%
      confidence intervals (CIs). RESULTS: We identified 286 incident cases of
      Parkinson disease during follow-up. Multivariable adjusted hazard ratios were
      1.06 (95% CI 0.76-1.47) for sitting time >=6 vs <6 hours per day; and 1.13 (95%
      CI 0.60-2.12) for body mass index >=30 vs <25 kg/m2. Results did not differ by
      sex. CONCLUSIONS: No association between prolonged sitting time per day or
      obesity and risk of Parkinson disease was found.

PMID- 29661902
TI  - Brain structure and cognition 3 years after the end of an early menopausal
      hormone therapy trial.
AB  - OBJECTIVE: The effects of 2 frequently used formulations of menopausal hormone
      therapy (mHT) on brain structure and cognition were investigated 3 years after
      the end of a randomized, placebo-controlled trial in recently menopausal women
      with good cardiovascular health. METHODS: Participants (aged 42-56 years; 5-36
      months past menopause) were randomized to one of the following: 0.45 mg/d oral
      conjugated equine estrogen (oCEE); 50 MUg/d transdermal 17beta-estradiol (tE2);
      or placebo pills and patch for 4 years. Oral progesterone (200 mg/d) was given to
      mHT groups for 12 days each month. MRIs were performed at baseline, at the end of
      4 years of mHT, and 3 years after the end of mHT (n = 75). A subset of
      participants also underwent Pittsburgh compound B-PET (n = 68). RESULTS:
      Ventricular volumes increased more in the oCEE group compared to placebo during
      the 4 years of mHT, but the increase in ventricular volumes was not different
      from placebo 3 years after the discontinuation of mHT. Increase in white matter
      hyperintensity volume was similar in the oCEE and tE2 groups, but it was
      statistically significantly greater than placebo only in the oCEE group. The
      longitudinal decline in dorsolateral prefrontal cortex volumes was less in the
      tE2 group compared to placebo, which correlated with lower cortical Pittsburgh
      compound B uptake. Rates of global cognitive change in mHT groups were not
      different from placebo. CONCLUSIONS: The effects of oCEE on global brain
      structure during mHT subside after oCEE discontinuation but white matter
      hyperintensities continue to increase. The relative preservation of dorsolateral
      prefrontal cortical volume in the tE2 group over 7 years indicates that mHT may
      have long-term effects on the brain. CLASSIFICATION OF EVIDENCE: This study
      provides Class III evidence that the rates of change in global brain volumes and
      cognitive function in recently menopausal women receiving mHT (tE2 or oCEE) were
      not significantly different from women receiving placebo, as measured 3 years
      after exposure to mHT.

PMID- 29661901
TI  - Megalencephalic leukoencephalopathy with subcortical cysts: Characterization of
      disease variants.
AB  - OBJECTIVE: To provide an overview of clinical and MRI characteristics of the
      different variants of the leukodystrophy megalencephalic leukoencephalopathy with
      subcortical cysts (MLC) and identify possible differentiating features. METHODS:
      We performed an international multi-institutional, cross-sectional observational
      study of the clinical and MRI characteristics in patients with genetically
      confirmed MLC. Clinical information was obtained by questionnaires for physicians
      and retrospective chart review. RESULTS: We included 204 patients with classic
      MLC, 187 of whom had recessive mutations in MLC1 (MLC1 variant) and 17 in
      GLIALCAM (MLC2A variant) and 38 patients with remitting MLC caused by dominant
      GLIALCAM mutations (MLC2B variant). We observed a relatively wide variability in
      neurologic disability among patients with classic MLC. No clinical differences
      could be identified between patients with MLC1 and MLC2A. Patients with MLC2B
      invariably had a milder phenotype with preservation of motor function, while
      intellectual disability and autism were relatively frequent. Systematic MRI
      review revealed no MRI features that distinguish between MLC1 and MLC2A.
      Radiologic improvement was observed in all patients with MLC2B and also in 2
      patients with MLC1. In MRIs obtained in the early disease stage, absence of
      signal abnormalities of the posterior limb of the internal capsule and cerebellar
      white matter and presence of only rarefied subcortical white matter instead of
      true subcortical cysts were suggestive of MLC2B. CONCLUSION: Clinical and MRI
      features did not distinguish between classic MLC with MLC1 or GLIALCAM mutations.
      Absence of signal abnormalities of the internal capsule and cerebellar white
      matter are MRI findings that point to the remitting phenotype.

PMID- 29661904
TI  - Increased cerebral functional connectivity in ALS: A resting-state
      magnetoencephalography study.
AB  - OBJECTIVE: We sought to assess cortical function in amyotrophic lateral sclerosis
      (ALS) using noninvasive neural signal recording. METHODS: Resting-state
      magnetoencephalography was used to measure power fluctuations in neuronal
      oscillations from distributed cortical parcels in 24 patients with ALS and 24
      healthy controls. A further 9 patients with primary lateral sclerosis and a group
      of 15 asymptomatic carriers of genetic mutations associated with ALS were also
      studied. RESULTS: Increased functional connectivity, particularly from the
      posterior cingulate cortex, was demonstrated in both patient groups compared to
      healthy controls. Directionally similar patterns were also evident in the
      asymptomatic genetic mutation carrier group. CONCLUSION: Increased cortical
      functional connectivity elevation is a quantitative marker that reflects ALS
      pathology across its clinical spectrum, and may develop during the presymptomatic
      period. The amelioration of pathologic magnetoencephalography signals might be a
      marker sensitive enough to provide proof-of-principle in the development of
      future neuroprotective therapeutics.

PMID- 29661906
TI  - Clinical Reasoning: A young woman with symmetric weakness and behavioral
      disturbance.

PMID- 29661905
TI  - Randomized study of adjunctive belimumab in participants with generalized
      myasthenia gravis.
AB  - OBJECTIVE: To investigate the efficacy and safety of belimumab, a fully human
      immunoglobulin G1lambda monoclonal antibody against B-lymphocyte stimulator, in
      participants with generalized myasthenia gravis (MG) who remained symptomatic
      despite standard of care (SoC) therapy. METHODS: Eligible participants with MG
      were randomized 1:1 to receive IV belimumab 10 mg/kg or placebo in this phase II,
      placebo-controlled, multicenter, double-blind study (NCT01480596; BEL115123).
      Participants received SoC therapies throughout the 24-week treatment phase and 12
      week follow-up period. The primary efficacy endpoint was mean change from
      baseline in the Quantitative Myasthenia Gravis (QMG) scale at week 24; safety
      assessments included the frequency and severity of adverse events (AEs) and
      serious AEs. RESULTS: Forty participants were randomized (placebo n = 22;
      belimumab n = 18). The mean change in QMG score from baseline at week 24 was not
      significantly different for belimumab vs placebo (p = 0.256). There were no
      statistically significant differences between treatment groups for secondary
      endpoints, including the MG Composite and MG-Activity of Daily Living scores.
      Acetylcholine receptor antibody levels decreased over time in both treatment
      groups. No unexpected AEs were identified and occurrence was similar in the
      belimumab (78%) and placebo (91%) groups. One participant receiving placebo died
      (severe sepsis) during the treatment phase. CONCLUSIONS: The primary endpoint was
      not met for belimumab in participants with generalized MG receiving SoC. There
      was no significant difference in mean change in the QMG score at week 24 for
      belimumab vs placebo. The safety profile of belimumab was consistent with
      previous systemic lupus erythematosus studies. CLASSIFICATION OF EVIDENCE: This
      study provides Class I evidence that for participants with generalized MG,
      belimumab did not significantly improve QMG score compared with placebo.

PMID- 29661907
TI  - Teaching NeuroImages: Facial ulceration in stroke: An unusual and lesser-known
      complication described by Wallenberg.

PMID- 29661908
TI  - Teaching NeuroImages: DWI and EEG findings in Creutzfeldt-Jakob disease.

PMID- 29661909
TI  - A novel combination treatment against melanoma with NRAS mutation and therapy
      resistance.

PMID- 29661910
TI  - Myeloid cell deficiency of p38gamma/p38delta protects against candidiasis and
      regulates antifungal immunity.
AB  - Candida albicans is a frequent aetiologic agent of sepsis associated with high
      mortality in immunocompromised patients. Developing new antifungal therapies is a
      medical need due to the low efficiency and resistance to current antifungal
      drugs. Here, we show that p38gamma and p38delta regulate the innate immune
      response to C. albicans We describe a new TAK1-TPL2-MKK1-ERK1/2 pathway in
      macrophages, which is activated by Dectin-1 engagement and positively regulated
      by p38gamma/p38delta. In mice, p38gamma/p38delta deficiency protects against C.
      albicans infection by increasing ROS and iNOS production and thus the antifungal
      capacity of neutrophils and macrophages, and by decreasing the hyper-inflammation
      that leads to severe host damage. Leucocyte recruitment to infected kidneys and
      production of inflammatory mediators are decreased in p38gamma/delta-null mice,
      reducing septic shock. p38gamma/p38delta in myeloid cells are critical for this
      effect. Moreover, pharmacological inhibition of p38gamma/p38delta in mice reduces
      fungal burden, revealing that these p38MAPKs may be therapeutic targets for
      treating C. albicans infection in humans.

PMID- 29661912
TI  - Microtubule end tethering of a processive kinesin-8 motor Kif18b is required for
      spindle positioning.
AB  - Mitotic spindle positioning specifies the plane of cell division during anaphase.
      Spindle orientation and positioning are therefore critical to ensure symmetric
      division in mitosis and asymmetric division during development. The control of
      astral microtubule length plays an essential role in positioning the spindle. In
      this study, using gene knockout, we show that the kinesin-8 Kif18b controls
      microtubule length to center the mitotic spindle at metaphase. Using in vitro
      reconstitution, we reveal that Kif18b is a highly processive plus end-directed
      motor that uses a C-terminal nonmotor microtubule-binding region to accumulate at
      growing microtubule plus ends. This region is regulated by phosphorylation to
      spatially control Kif18b accumulation at plus ends and is essential for Kif18b
      dependent spindle positioning and regulation of microtubule length. Finally, we
      demonstrate that Kif18b shortens microtubules by increasing the catastrophe rate
      of dynamic microtubules. Overall, our work reveals that Kif18b uses its motile
      properties to reach microtubule ends, where it regulates astral microtubule
      length to ensure spindle centering.

PMID- 29661911
TI  - PATL2 is a key actor of oocyte maturation whose invalidation causes infertility
      in women and mice.
AB  - The genetic causes of oocyte meiotic deficiency (OMD), a form of primary
      infertility characterised by the production of immature oocytes, remain largely
      unexplored. Using whole exome sequencing, we found that 26% of a cohort of 23
      subjects with OMD harboured the same homozygous nonsense pathogenic mutation in
      PATL2, a gene encoding a putative RNA-binding protein. Using Patl2 knockout mice,
      we confirmed that PATL2 deficiency disturbs oocyte maturation, since oocytes and
      zygotes exhibit morphological and developmental defects, respectively. PATL2's
      amphibian orthologue is involved in the regulation of oocyte mRNA as a partner of
      CPEB However, Patl2's expression profile throughout oocyte development in mice,
      alongside colocalisation experiments with Cpeb1, Msy2 and Ddx6 (three oocyte RNA
      regulators) suggest an original role for Patl2 in mammals. Accordingly,
      transcriptomic analysis of oocytes from WT and Patl2-/- animals demonstrated that
      in the absence of Patl2, expression levels of a select number of highly relevant
      genes involved in oocyte maturation and early embryonic development are
      deregulated. In conclusion, PATL2 is a novel actor of mammalian oocyte maturation
      whose invalidation causes OMD in humans.

PMID- 29661913
TI  - Premenstrual syndrome and alcohol consumption: a systematic review and meta
      analysis.
AB  - OBJECTIVE: Premenstrual syndrome (PMS) is a very common disorder worldwide which
      carries an important economic burden. We conducted a systematic review and a meta
      analysis to assess the role of alcohol in the occurrence of PMS. METHODS: We
      searched MEDLINE, EMBASE, the five regional bibliographic databases of the WHO,
      the Proceedings database and the Open Access Thesis and Dissertations (OATD) from
      inception to May 2017. We also reviewed the references of every article retrieved
      and established personal contact with researchers to trace further publications
      or reports. We did not include any language limitations. Studies were included
      if: (1) they presented original data from cohort, case-control or cross-sectional
      studies, (2) PMS was clearly defined as the outcome of interest, (3) one of the
      exposure factors was alcohol consumption, (4) they provided estimates of odds
      ratios, relative risks, or any other effect measure and their confidence
      intervals, or enough data to calculate them. RESULTS: We identified 39 studies of
      which 19 were eligible. Intake of alcohol was associated with a moderate increase
      in the risk of PMS (OR=1.45, 95% CI: 1.17 to 1.79). Heavy drinking yielded a
      larger increase in the risk than any drinking (OR=1.79, 95% CI: 1.39 to 2.32).
      DISCUSSION: Our results suggest that alcohol intake presents a moderate
      association with PMS risk. Future studies should avoid cross-sectional designs
      and focus on determining whether there is a threshold of alcohol intake under
      which the harmful effect on PMS is non-existent.

PMID- 29661914
TI  - Trends, geographical variation and factors associated with prescribing of gluten
      free foods in English primary care: a cross-sectional study.
AB  - OBJECTIVES: There is substantial disagreement about whether gluten-free foods
      should be prescribed on the National Health Service. We aim to describe time
      trends, variation and factors associated with prescribing gluten-free foods in
      England. SETTING: English primary care. PARTICIPANTS: English general practices.
      PRIMARY AND SECONDARY OUTCOME MEASURES: We described long-term national trends in
      gluten-free prescribing, and practice and Clinical Commissioning Group (CCG)
      level monthly variation in the rate of gluten-free prescribing (per 1000
      patients) over time. We used a mixed-effect Poisson regression model to determine
      factors associated with gluten-free prescribing rate. RESULTS: There were 1.3
      million gluten-free prescriptions between July 2016 and June 2017, down from 1.8
      million in 2012/2013, with a corresponding cost reduction from L25.4 million to
      L18.7 million. There was substantial variation in prescribing rates among
      practices (range 0 to 148 prescriptions per 1000 patients, IQR 7.3-31.8), driven
      in part by substantial variation at the CCG level, likely due to differences in
      prescribing policy. Practices in the most deprived quintile of deprivation score
      had a lower prescribing rate than those in the highest quintile (incidence rate
      ratio 0.89, 95% CI 0.87 to 0.91). This is potentially a reflection of the lower
      rate of diagnosed coeliac disease in more deprived populations. CONCLUSION:
      Gluten-free prescribing is in a state of flux, with substantial clinically
      unwarranted variation between practices and CCGs.

PMID- 29661915
TI  - Residues contributing to drug transport by ABCG2 are localised to multiple drug
      binding pockets.
AB  - Multidrug binding and transport by the ATP-binding cassette transporter ABCG2 is
      a factor in the clinical resistance to chemotherapy in leukaemia, and a
      contributory factor to the pharmacokinetic profiles of many other prescribed
      drugs. Despite its importance, the structural basis of multidrug transport, i.e.
      the ability to transport multiple distinct chemicals, has remained elusive.
      Previous research has shown that at least two residues positioned towards the
      cytoplasmic end of transmembrane helix 3 (TM3) of the transporter play a role in
      drug transport. We hypothesised that other residues, either in the longitudinal
      span of TM3, or a perpendicular slice through the intracellular end of other TM
      helices would also contribute to drug binding and transport by ABCG2. Single
      point mutant isoforms of ABCG2 were made at ~30 positions and were analysed for
      effects on protein expression, localisation (western blotting, confocal
      microscopy) and function (flow cytometry) in a mammalian stable cell line
      expression system. Our data were interpreted in terms of recent structural data
      on the ABCG protein subfamily and enabled us to propose a surface-binding site
      for the drug mitoxantrone (MX) as well as a second, buried site for the same
      drug. Further mutational analysis of residues that spatially separate these two
      sites prompts us to suggest a molecular and structural pathway for MX transport
      by ABCG2.

PMID- 29661916
TI  - Sustained Reduction in Severe Hypoglycemia in Adults With Type 1 Diabetes
      Complicated by Impaired Awareness of Hypoglycemia: Two-Year Follow-up in the
      HypoCOMPaSS Randomized Clinical Trial.
AB  - OBJECTIVE: Severe hypoglycemia is a feared complication of type 1 diabetes; yet,
      few trials have targeted prevention using optimized self-management (educational,
      therapeutic, and technological support). We aimed to investigate whether improved
      awareness and reduced severe hypoglycemia, achieved during an intensive
      randomized clinical trial (RCT), were sustained after return to routine care.
      RESEARCH DESIGN AND METHODS: Ninety-six adults with type 1 diabetes (29 +/- 12
      years' duration) and impaired awareness of hypoglycemia at five U.K. tertiary
      referral diabetes centers were recruited into a 24-week 2 * 2 factorial RCT
      (HypoCOMPaSS). Participants were randomized to pump (continuous subcutaneous
      insulin infusion [CSII]) or multiple daily injections (MDIs) and real-time
      continuous glucose monitoring (RT-CGM) or self-monitoring of blood glucose
      (SMBG), with equal education/attention to all groups. At 24 weeks, participants
      returned to routine care with follow-up until 24 months, including free choice of
      MDI/CSII; RT-CGM vs. SMBG comparison continued to 24 months. Primary outcome was
      mean difference (baseline to 24 months [between groups]) in hypoglycemia
      awareness. RESULTS: Improvement in hypoglycemia awareness was sustained (Gold
      score at baseline 5.1 +/- 1.1 vs. 24 months 3.7 +/- 1.9; P < 0.0001). Severe
      hypoglycemia rate was reduced from 8.9 +/- 12.8 episodes/person-year over the 12
      months prestudy to 0.4 +/- 0.8 over 24 months (P < 0.0001). HbA1c improved
      (baseline 8.2 +/- 3.2% [66 +/- 12 mmol/mol] vs. 24 months 7.7 +/- 3.1% [61 +/- 10
      mmol/mol]; P = 0.003). Improvement in treatment satisfaction and reduced fear of
      hypoglycemia were sustained. There were no significant differences between
      interventions at 24 months. CONCLUSIONS: Optimized insulin replacement and
      glucose monitoring underpinned by hypoglycemia-focused structured education
      should be provided to all with type 1 diabetes complicated by impaired awareness
      of hypoglycemia.

PMID- 29661918
TI  - Characteristics of new solid nodules detected in incidence screening rounds of
      low-dose CT lung cancer screening: the NELSON study.
AB  - PURPOSE: New nodules after baseline are regularly found in low-dose CT lung
      cancer screening and have a high lung cancer probability. It is unknown whether
      morphological and location characteristics can improve new nodule risk
      stratification by size. METHODS: Solid non-calcified nodules detected during
      incidence screening rounds of the randomised controlled Dutch-Belgian lung cancer
      screening (NELSON) trial and registered as new or previously below detection
      limit (15 mm3) were included. A multivariate logistic regression analysis with
      lung cancer as outcome was performed, including previously established volume cut
      offs (<30 mm3, 30-<200 mm3 and >=200 mm3) and nodule characteristics (location,
      distribution, shape, margin and visibility <15 mm3 in retrospect). RESULTS:
      Overall, 1280 new nodules were included with 73 (6%) being lung cancer. Of
      nodules >=30 mm3 at detection and visible <15 mm3 in retrospect, 22% (6/27) were
      lung cancer. Discrimination based on volume cut-offs (area under the receiver
      operating characteristic curve (AUC): 0.80, 95% CI 0.75 to 0.84) and continuous
      volume (AUC: 0.82, 95% CI 0.77 to 0.87) was similar. After adjustment for volume
      cut-offs, only location in the right upper lobe (OR 2.0, P=0.012), central
      distribution (OR 2.4, P=0.001) and visibility <15 mm3 in retrospect (OR 4.7,
      P=0.003) remained significant predictors for lung cancer. The Hosmer-Lemeshow
      test (P=0.75) and assessment of bootstrap calibration curves indicated adequate
      model fit. Discrimination based on the continuous model probability (AUC: 0.85,
      95% CI 0.81 to 0.89) was superior to volume cut-offs alone, but when stratified
      into three risk groups (AUC: 0.82, 95% CI 0.78 to 0.86), discrimination was
      similar. CONCLUSION: Contrary to morphological nodule characteristics, growth
      independent characteristics may further improve volume-based new nodule lung
      cancer prediction, but in a three-category stratification approach, this is
      limited. TRIAL REGISTRATION NUMBER: ISRCTN63545820; pre-results.

PMID- 29661917
TI  - Association of Hemoglobin A1c and Wound Healing in Diabetic Foot Ulcers.
AB  - OBJECTIVE: This study evaluated the association between hemoglobin A1c (A1C) and
      wound outcomes in patients with diabetic foot ulcers (DFUs). RESEARCH DESIGN AND
      METHODS: We conducted a retrospective analysis of an ongoing prospective, clinic
      based study of patients with DFUs treated at an academic institution during a 4.7
      year period. Data from 270 participants and 584 wounds were included in the
      analysis. Cox proportional hazards regression was used to assess the incidence of
      wound healing at any follow-up time in relation to categories of baseline A1C and
      the incidence of long-term (>=90 days) wound healing in relation to tertiles of
      nadir A1C change and mean A1C change from baseline, adjusted for potential
      confounders. RESULTS: Baseline A1C was not associated with wound healing in
      univariate or fully adjusted models. Compared with a nadir A1C change from
      baseline of -0.29 to 0.0 (tertile 2), a nadir A1C change of 0.09 to 2.4 (tertile
      3) was positively associated with long-term wound healing in the subset of
      participants with baseline A1C <7.5% (hazard ratio [HR] 2.07; 95% CI 1.08-4.00),
      but no association with wound healing was seen with the mean A1C change from
      baseline in this group. Neither nadir A1C change nor mean A1C change were
      associated with long-term wound healing in participants with baseline A1C >=7.5%.
      CONCLUSIONS: There does not appear to be a clinically meaningful association
      between baseline or prospective A1C and wound healing in patients with DFUs. The
      paradoxical finding of accelerated wound healing and increase in A1C in
      participants with better baseline glycemic control requires confirmation in
      further studies.

PMID- 29661919
TI  - Moving more: our heart cares but do our lungs?

PMID- 29661920
TI  - DHTKD1 Deficiency Causes Charcot-Marie-Tooth Disease in Mice.
AB  - DHTKD1, a part of 2-ketoadipic acid dehydrogenase complex, is involved in lysine
      and tryptophan catabolism. Mutations in DHTKD1 block the metabolic pathway and
      cause 2-aminoadipic and 2-oxoadipic aciduria (AMOXAD), an autosomal recessive
      inborn metabolic disorder. In addition, a nonsense mutation in DHTKD1 that we
      identified previously causes Charcot-Marie-Tooth disease (CMT) type 2Q, one of
      the most common inherited neurological disorders affecting the peripheral nerves
      in the musculature. However, the comprehensive molecular mechanism underlying
      CMT2Q remains elusive. Here, we show that Dhtkd1-/- mice mimic the major aspects
      of CMT2 phenotypes, characterized by progressive weakness and atrophy in the
      distal parts of limbs with motor and sensory dysfunctions, which are accompanied
      with decreased nerve conduction velocity. Moreover, DHTKD1 deficiency causes
      severe metabolic abnormalities and dramatically increased levels of 2-ketoadipic
      acid (2-KAA) and 2-aminoadipic acid (2-AAA) in urine. Further studies revealed
      that both 2-KAA and 2-AAA could stimulate insulin biosynthesis and secretion.
      Subsequently, elevated insulin regulates myelin protein zero (Mpz) transcription
      in Schwann cells via upregulating the expression of early growth response 2
      (Egr2), leading to myelin structure damage and axonal degeneration. Finally, 2
      AAA-fed mice do reproduce phenotypes similar to CMT2Q phenotypes. In conclusion,
      we have demonstrated that loss of DHTKD1 causes CMT2Q-like phenotypes through
      dysregulation of Mpz mRNA and protein zero (P0) which are closely associated with
      elevated DHTKD1 substrate and insulin levels. These findings further indicate an
      important role of metabolic disorders in addition to mitochondrial insufficiency
      in the pathogenesis of peripheral neuropathies.

PMID- 29661921
TI  - Poly(ADP-Ribose) Polymerase 1 Promotes the Human Heat Shock Response by
      Facilitating Heat Shock Transcription Factor 1 Binding to DNA.
AB  - The heat shock response (HSR) is characterized by the rapid and robust induction
      of heat shock proteins (HSPs), including HSP70, in response to heat shock and is
      regulated by heat shock transcription factor 1 (HSF1) in mammalian cells.
      Poly(ADP-ribose) polymerase 1 (PARP1), which can form a complex with HSF1 through
      the scaffold protein PARP13, has been suggested to be involved in the HSR.
      However, its effects on and the regulatory mechanisms of the HSR are not well
      understood. Here we show that prior to heat shock, the HSF1-PARP13-PARP1 complex
      binds to the HSP70 promoter. In response to heat shock, activated and auto
      PARylated PARP1 dissociates from HSF1-PARP13 and is redistributed throughout the
      HSP70 locus. Remarkably, chromatin in the HSP70 promoter is initially PARylated
      at high levels and decondensed, whereas chromatin in the gene body is moderately
      PARylated afterwards. Activated HSF1 then binds to the promoter efficiently and
      promotes the HSR. Chromatin PARylation and HSF1 binding to the promoter are also
      facilitated by the phosphorylation-dependent dissociation of PARP13. Furthermore,
      the HSR and proteostasis capacity are reduced by pretreatment with genotoxic
      stresses, which disrupt the ternary complex. These results illuminate one of the
      priming mechanisms of the HSR that facilitates the binding of HSF1 to DNA during
      heat shock.

PMID- 29661922
TI  - Gpn2 and Rba50 Directly Participate in the Assembly of the Rpb3 Subcomplex in the
      Biogenesis of RNA Polymerase II.
AB  - RNA polymerase II (RNAPII) is one of the central enzymes in cell growth and
      organizational development. It is a large macromolecular complex consisting of 12
      subunits. Relative to the clear definition of RNAPII structure and biological
      function, the molecular mechanism of how RNAPII is assembled is poorly
      understood, and thus the key assembly factors acting for the assembly of RNAPII
      remain elusive. In this study, we identified two factors, Gpn2 and Rba50, that
      directly participate in the assembly of RNAPII. Gpn2 and Rba50 were demonstrated
      to interact with Rpb12 and Rpb3, respectively. An interaction between Gpn2 and
      Rba50 was also demonstrated. When Gpn2 and Rba50 are functionally defective, the
      assembly of the Rpb3 subcomplex is disrupted, leading to defects in the assembly
      of RNAPII. Based on these results, we conclude that Gpn2 and Rba50 directly
      participate in the assembly of the Rpb3 subcomplex and subsequently the
      biogenesis of RNAPII.

PMID- 29661923
TI  - Association between semantic dementia and progressive supranuclear palsy.

PMID- 29661924
TI  - C9orf72 expansion is associated with accelerated decline of respiratory function
      and decreased survival in amyotrophic lateral sclerosis.

PMID- 29661925
TI  - Changing antiepilepsy drug-prescribing trends in women with epilepsy in the UK
      and Ireland and the impact on major congenital malformations.
AB  - OBJECTIVES: After 20 years of data collection, pregnancy registers have informed
      prescribing practice. Various populations show trends for a reduction in
      valproate prescribing, which is associated with an increased risk of anatomical
      teratogenesis and neurodevelopmental effects in those exposed in utero. Our aim
      was to determine if any shifts in prescribing trends have occurred in the UK and
      Ireland Epilepsy and Pregnancy Register cohort and to assess if there had been
      any change in the overall major congenital malformation (MCM) rate over time.
      METHODS: The UK and Ireland Epilepsy and Pregnancy Register, a prospective,
      observational, registration and follow-up study established in 1996, was used to
      determine the changes in antiepileptic drugs (AEDs) utilised during pregnancy and
      the MCM rate between 1996 and 2016. Linear regression analysis was used to assess
      changes in AED utilisation, and Poisson regression was used for the analysis of
      trends in the MCM rates. RESULTS: Outcome data for 9247 pregnancies showed a
      stable percentage of monotherapy to polytherapy prescribing habits over time.
      After Bonferroni correction, statistically significant (p<0.003) changes were
      found in monotherapy prescribing with increases in lamotrigine and levetiracetam
      and decreases in valproate and carbamazepine use. Between 1996 and 2016, the
      total MCM rate showed a 2.1% reduction per year (incidence risk ratio 0.979 (95%
      CIs 0.956 to 1.002) but Poisson regression analysis showed that this was not
      statistically significant p=0.08). CONCLUSION: Significant changes are seen in
      the prescribing habits in this cohort over 20 years, but a statistically
      significant change in the MCM rate was not detected. This work should be
      replicated on a larger scale to determine if significant changes are occurring in
      the MCM rate, which would allow a robust economic estimate of the benefits of
      improvements in prescribing practice and the personal effect of such changes.

PMID- 29661926
TI  - Disruptions in gut microbial-host co-metabolism and the development of metabolic
      disorders.
AB  - The microbial-mammalian metabolic axis has become recognized as an important
      component governing the overall homeostatic balance of the mammalian host.
      Disruption of the state of homeostasis among the gut microbiota has been shown to
      be causally linked to the development of host metabolic diseases including
      obesity, cardiovascular, diabetes, and fatty liver disease. This disruption is
      often referred to as gut dysbiosis. Gut dysbiosis leads to altered metabolic
      products derived from the microbiota and these in turn, typically shift the
      homeostatic metabolic balance of the host towards a low-grade chronic
      inflammation, a hallmark of metabolic syndrome. The primary objective of this
      review is to examine and discuss some very current research that has been done to
      study the effect of bacterial metabolites on host metabolism, sometimes referred
      to as microbiota-host co-metabolism. The metabolic conditions reviewed here
      include obesity, a known risk factor for all of the other metabolic conditions,
      as well as, cardiovascular disease, diabetes and nonalcoholic fatty liver
      disease. Only by further understanding the cause and result of gut dysbiosis will
      an adequate solution be found for metabolic disease, a viewpoint shared by many.

PMID- 29661927
TI  - T Cell-Independent Gamma Interferon and B Cells Cooperate To Prevent Mortality
      Associated with Disseminated Chlamydia muridarum Genital Tract Infection.
AB  - CD4 T cells and antibody are required for optimal acquired immunity to Chlamydia
      muridarum genital tract infection, and T cell-mediated gamma interferon (IFN
      gamma) production is necessary to clear infection in the absence of humoral
      immunity. However, the role of T cell-independent immune responses during primary
      infection remains unclear. We investigated this question by inoculating wild-type
      and immune-deficient mice with C. muridarum CM001, a clonal isolate capable of
      enhanced extragenital replication. Genital inoculation of wild-type mice resulted
      in transient dissemination to the lungs and spleen that then was rapidly cleared
      from these organs. However, CM001 genital infection proved lethal for STAT1-/-
      and IFNG-/- mice, in which IFN-gamma signaling was absent, and for Rag1-/- mice,
      which lacked T and B cells and in which innate IFN-gamma signaling was retained.
      In contrast, B cell-deficient muMT mice, which can generate a Th1 response, and T
      cell-deficient mice with intact B cell and innate IFN-gamma signaling survived.
      These data collectively indicate that IFN-gamma prevents lethal CM001
      dissemination in the absence of T cells and suggests a B cell corequirement.
      Adoptive transfer of convalescent-phase immune serum but not naive IgM to Rag1-/-
      mice infected with CM001 significantly increased the survival time, while
      transfer of naive B cells completely rescued Rag1-/- mice from CM001 lethality.
      Protection was associated with a significant reduction in the lung chlamydial
      burden of genitally infected mice. These data reveal an important cooperation
      between T cell-independent B cell responses and innate IFN-gamma in chlamydial
      host defense and suggest that interactions between T cell-independent antibody
      and IFN-gamma are essential for limiting extragenital dissemination.

PMID- 29661928
TI  - Identification and Evaluation of Novel Protective Antigens for the Development of
      a Candidate Tuberculosis Subunit Vaccine.
AB  - The development of a vaccine against tuberculosis (TB), a disease caused by
      Mycobacterium tuberculosis, is urgently needed. The only currently available
      vaccine, M. bovis BCG, has variable efficacy. One approach in the global vaccine
      development effort is focused on boosting BCG using subunit vaccines. The
      identification of novel antigens for inclusion in subunit vaccines is a critical
      step in the TB vaccine development pathway. We selected four novel mycobacterial
      antigens recognized during the course of human infection. A replication-deficient
      chimpanzee adenovirus (ChAdOx1) was constructed to express each antigen
      individually, and these vectors were evaluated for protective efficacy in murine
      M. tuberculosis challenge experiments. One antigen, PPE15 (Rv1039c), conferred
      significant and reproducible protection when administered alone and as a boost to
      BCG vaccination. We identified immunodominant epitopes to define the protective
      immune responses using tetramers and intravascular staining. Lung parenchymal
      CD4+ and CD8+ CXCR3+ KLRG1- T cells, previously associated with protection
      against M. tuberculosis, were enriched in the vaccinated groups compared to the
      control groups. Further work to evaluate the protective efficacy of PPE15 in more
      stringent preclinical animal models, together with the identification of further
      novel protective antigens using this selection strategy, is now merited.

PMID- 29661929
TI  - Arginase-1 Expression in Myeloid Cells Regulates Staphylococcus aureus Planktonic
      but Not Biofilm Infection.
AB  - Staphylococcus aureus is a leading cause of device-associated biofilm infections,
      which represent a serious health care concern based on their chronicity and
      antibiotic resistance. We previously reported that S. aureus biofilms
      preferentially recruit myeloid-derived suppressor cells (MDSCs), which promote
      monocyte and macrophage anti-inflammatory properties. This is associated with
      increased myeloid arginase-1 (Arg-1) expression, which has been linked to anti
      inflammatory and profibrotic activities that are observed during S. aureus
      biofilm infections. To determine whether MDSCs and macrophages utilize Arg-1 to
      promote biofilm infection, Arg-1 was deleted in myeloid cells by use of Tie-2Cre
      mice. Despite Arg-1 expression in biofilm-associated myeloid cells, bacterial
      burdens and leukocyte infiltrates were similar between wild-type (WT) and Arg
      1fl/fl;Tie-2Cre conditional knockout (KO) mice from days 3 to 14 postinfection in
      both orthopedic implant and catheter-associated biofilm models. However,
      inducible nitric oxide synthase (iNOS) expression was dramatically elevated in
      biofilm-associated MDSCs from Arg-1fl/fl;Tie-2Cre animals, suggesting a potential
      Arg-1-independent compensatory mechanism for MDSC-mediated immunomodulation.
      Treatment of Arg-1fl/fl;Tie-2Cre mice with the iNOS inhibitor N6-(1-iminoethyl)-l
      lysine (l-NIL) had no effect on biofilm burdens or immune infiltrates, whereas
      treatment of WT mice with the Arg-1/ornithine decarboxylase inhibitor
      difluoromethylornithine (DFMO) increased bacterial titers, but only in the
      surrounding soft tissues, which possess attributes of a planktonic environment. A
      role for myeloid-derived Arg-1 in regulating planktonic infection was confirmed
      using a subcutaneous abscess model, in which S. aureus burdens were significantly
      increased in Arg-1fl/fl;Tie-2Cre mice compared to those in WT mice. Collectively,
      these results indicate that the effects of myeloid Arg-1 are context dependent
      and are manifest during planktonic but not biofilm infection.

PMID- 29661930
TI  - The Critical Role of Zinc in a New Murine Model of Enterotoxigenic E. coli (ETEC)
      Diarrhea.
AB  - Enterotoxigenic E. coli are major causes of traveler's diarrhea as well as
      endemic diarrhea and stunting in children in developing areas. However a small
      mammal model has been badly needed to better understand and assess mechanisms,
      vaccines and interventions. We report a murine model of ETEC diarrhea, weight
      loss and enteropathy, and investigate the role of zinc on the outcomes. LT+ST
      producing enterotoxigenic E. coli (ETEC) given to weaned C57BL/6 mice after
      antibiotic disruption of normal microbiota cause growth impairment, watery
      diarrhea, heavy stool shedding and mild to moderate intestinal inflammation, the
      latter worse with zinc deficiency. Zinc treatment promoted growth in zinc
      deficient infected mice, and subinhibitory zinc reduced expression of ETEC
      virulence genes cfa1, cexE, sta2 and degP, but not eltA in vitro. Zinc
      supplementation increased shedding and ileal burden of WT ETEC, but decreased
      shedding and tissue burden of LTKO ETEC. LTKO ETEC infected mice had delayed
      disease onset and also had less inflammation by fecal MPO assessment These
      findings provide a new murine model of ETEC infection that can help elucidate
      mechanisms of growth, diarrhea and inflammatory responses as well as potential
      vaccines and interventions.

PMID- 29661931
TI  - Role of Neuraminidase-Producing Bacteria in Exposing Cryptic Carbohydrate
      Receptors for Streptococcus gordonii Adherence.
AB  - Streptococcus gordonii is an early colonizer of the oral cavity. Although a
      variety of S. gordonii adherence mechanisms have been described, current dogma is
      that the major receptor for S. gordonii is sialic acid. However, as many
      bacterial species in the oral cavity produce neuraminidase that can cleave
      terminal sialic acid, it is unclear whether S. gordonii relies on sialic acid for
      adherence to oral surfaces or if this species has developed alternative binding
      strategies. Previous studies have examined adherence to immobilized
      glycoconjugates and identified binding to additional glycans, but no prior
      studies have defined the contribution of these different glycan structures in
      adherence to oral epithelial cells. We determined that the majority of S.
      gordonii strains tested did not rely on sialic acid for efficient adherence. In
      fact, adherence of some strains was significantly increased following
      neuraminidase treatment. Further investigation of representative strains that do
      not rely on sialic acid for adherence revealed binding not only to sialic acid
      via the serine-rich repeat protein GspB but also to beta-1,4-linked galactose.
      Adherence to this carbohydrate occurs via an unknown adhesin distinct from those
      utilized by Streptococcus oralis and Streptococcus pneumoniae Demonstrating the
      potential biological relevance of binding to this cryptic receptor, we
      established that S. oralis increases S. gordonii adherence in a neuraminidase
      dependent manner. These data suggest that S. gordonii has evolved to
      simultaneously utilize both terminal and cryptic receptors in response to the
      production of neuraminidase by other species in the oral environment.

PMID- 29661932
TI  - Chlamydia muridarum Genital and Gastrointestinal Infection Tropism Is Mediated by
      Distinct Chromosomal Factors.
AB  - Some members of the genus Chlamydia, including the human pathogen Chlamydia
      trachomatis, infect multiple tissues, including the genital and gastrointestinal
      (GI) tracts. However, it is unknown if bacterial targeting to these sites is
      mediated by multifunctional or distinct chlamydial factors. We previously showed
      that disruption of individual large clostridial toxin homologs encoded within the
      Chlamydia muridarum plasticity zone were not critical for murine genital tract
      infection. Here, we assessed whether cytotoxin genes contribute to C. muridarum
      GI tropism. Infectivity and shedding of wild-type (WT) C. muridarum and three
      mutants containing nonsense mutations in different cytotoxin genes, tc0437,
      tc0438, and tc0439, were compared in mouse genital and GI infection models. One
      mutant, which had a nonsense mutation in tc0439, was highly attenuated for GI
      infection and had a GI 50% infectious dose (ID50) that was 1,000 times greater
      than that of the WT. GI inoculation with this mutant failed to elicit anti
      chlamydial antibodies or to protect against subsequent genital tract infection.
      Genome sequencing of the tc0439 mutant revealed additional chromosomal mutations,
      and phenotyping of additional mutants suggested that the GI attenuation might be
      linked to a nonsense mutation in tc0600 The molecular mechanism underlying this
      dramatic difference in tissue-tropic virulence is not fully understood. However,
      isolation of these mutants demonstrates that distinct chlamydial chromosomal
      factors mediate chlamydial tissue tropism and provides a basis for vaccine
      initiatives to isolate chlamydia strains that are attenuated for genital
      infection but retain the ability to colonize the GI tract and elicit protective
      immune responses.

PMID- 29661933
TI  - Interleukin-22 Immunotherapy during Severe Influenza Enhances Lung Tissue
      Integrity and Reduces Secondary Bacterial Systemic Invasion.
AB  - Severe bacterial (pneumococcal) infections are commonly associated with influenza
      and are significant contributors to the excess morbidity and mortality of
      influenza. Disruption of lung tissue integrity during influenza participates in
      bacterial pulmonary colonization and dissemination out of the lungs. Interleukin
      22 (IL-22) has gained considerable interest in anti-inflammatory and anti
      infection immunotherapy over the last decade. In the current study, we
      investigated the effect of exogenous IL-22 delivery on the outcome of
      pneumococcal superinfection postinfluenza. Our data show that exogenous treatment
      of influenza virus-infected mice with recombinant IL-22 reduces bacterial
      dissemination out of the lungs but is without effect on pulmonary bacterial
      burden. Reduced systemic bacterial dissemination was linked to reinforced
      pulmonary barrier functions, as revealed by total protein measurement in the
      bronchoalveolar fluids, intratracheal fluorescein isothiocyanate-dextran
      tracking, and histological approaches. We describe an IL-22-specific gene
      signature in the lung tissue of influenza A virus (IAV)-infected (and naive) mice
      that might explain the observed effects. Indeed, exogenous IL-22 modulates the
      gene expression profile in a way that suggests reinforcement of tissue integrity.
      Our results open the way to alternative approaches for limiting postinfluenza
      bacterial superinfection, particularly, systemic bacterial invasion.

PMID- 29661934
TI  - Nut consumption and incidence of seven cardiovascular diseases.
AB  - BACKGROUND: Nut consumption has been found to be inversely associated with
      cardiovascular disease mortality, but the association between nut consumption and
      incidence of specific cardiovascular diseases is unclear. We examined the
      association between nut consumption and incidence of seven cardiovascular
      diseases. METHODS: This prospective study included 61 364 Swedish adults who had
      completed a Food Frequency Questionnaire and were followed up for 17 years
      through linkage with the Swedish National Patient and Death Registers. RESULTS:
      Nut consumption was inversely associated with risk of myocardial infarction,
      heart failure, atrial fibrillation and abdominal aortic aneurysm in the age
      adjusted and sex-adjusted analysis. However, adjustment for multiple risk factors
      attenuated these associations and only a linear, dose-response, association with
      atrial fibrillation (ptrend=0.004) and a non-linear association (pnon
      linearity=0.003) with heart failure remained. Compared with no consumption of
      nuts, the multivariable HRs (95% CI) of atrial fibrillation across categories of
      nut consumption were 0.97 (0.93 to 1.02) for 1-3 times/month, 0.88 (0.79 to 0.99)
      for 1-2 times/week and 0.82 (0.68 to 0.99) for >=3 times/week. For heart failure,
      the corresponding HRs (95% CI) were 0.87 (0.80 to 0.94), 0.80 (0.67 to 0.97) and
      0.98 (0.76 to 1.27). Nut consumption was not associated with risk of aortic valve
      stenosis, ischaemic stroke or intracerebral haemorrhage. CONCLUSIONS: These
      findings suggest that nut consumption or factors associated with this nutritional
      behaviour may play a role in reducing the risk of atrial fibrillation and
      possibly heart failure. TRIAL REGISTRATION NUMBER: NCT01127711 and
      NCT01127698;Results.

PMID- 29661935
TI  - The labile iron pool attenuates peroxynitrite-dependent damage and can no longer
      be considered solely a pro-oxidative cellular iron source.
AB  - The ubiquitous cellular labile iron pool (LIP) is often associated with the
      production of the highly reactive hydroxyl radical, which forms through a redox
      reaction with hydrogen peroxide. Peroxynitrite is a biologically relevant
      peroxide produced by the recombination of nitric oxide and superoxide. It is a
      strong oxidant that may be involved in multiple pathological conditions, but
      whether and how it interacts with the LIP are unclear. Here, using fluorescence
      spectroscopy, we investigated the interaction between the LIP and peroxynitrite
      by monitoring peroxynitrite-dependent accumulation of nitrosated and oxidized
      fluorescent intracellular indicators. We found that, in murine macrophages,
      removal of the LIP with membrane-permeable iron chelators sustainably accelerates
      the peroxynitrite-dependent oxidation and nitrosation of these indicators. These
      observations could not be reproduced in cell-free assays, indicating that the
      chelator-enhancing effect on peroxynitrite-dependent modifications of the
      indicators depended on cell constituents, presumably including LIP, that react
      with these chelators. Moreover, neither free nor ferrous-complexed chelators
      stimulated intracellular or extracellular oxidative and nitrosative chemistries.
      On the basis of these results, LIP appears to be a relevant and competitive
      cellular target of peroxynitrite or its derived oxidants, and thereby it reduces
      oxidative processes, an observation that may change the conventional notion that
      the LIP is simply a cellular source of pro-oxidant iron.

PMID- 29661936
TI  - Ssy5 is a signaling serine protease that exhibits atypical biogenesis and marked
      S1 specificity.
AB  - Ssy5 is a signaling endoprotease that plays a key role in regulating central
      metabolism, cellular aging, and morphological transitions important for growth
      and survival of yeast (Saccharomyces cerevisiae) cells. In response to
      extracellular amino acids, Ssy5 proteolytically activates the transcription
      factors Stp1 and Stp2, leading to enhanced Ssy1-Ptr3-Ssy5 (SPS) sensor-regulated
      gene expression. Ssy5 comprises a catalytic (Cat) domain and an extensive
      regulatory prodomain. Ssy5 is refractory to both broad-spectrum and serine
      protease-specific inhibitors, confounding its classification as a protease, and
      no information about Ssy5's cleavage-site preferences and its mechanism of
      substrate selection is available. Here, using mutational and inhibition
      experiments, we investigated the biogenesis and catalytic properties of Ssy5 and
      conclusively show that it is a serine protease. Atypical for the majority of
      serine proteases, Ssy5's prodomain was obligatorily required in cis during
      biogenesis for the maturation of the proteolytic activity of the Cat domain.
      Autolysis and Stp1 and Stp2 cleavage occurred between a cysteine (at the P1 site)
      and a serine or alanine (at the P'1 site) and required residues with short side
      chains at the P1 site. Substitutions in the Cat domain affecting substrate
      specificity revealed that residues Phe-634, His-661, and Gly-671 in the S1
      binding pocket of this domain are important for Ssy5 catalytic function. This
      study confirms that the signaling protease Ssy5 is a serine protease and provides
      a detailed understanding of the biogenesis and intrinsic properties of this key
      enzyme in yeast.

PMID- 29661937
TI  - A charge-sensing region in the stromal interaction molecule 1 luminal domain
      confers stabilization-mediated inhibition of SOCE in response to S-nitrosylation.
AB  - Store-operated Ca2+ entry (SOCE) is a major Ca2+ signaling pathway facilitating
      extracellular Ca2+ influx in response to the initial release of intracellular
      endo/sarcoplasmic reticulum (ER/SR) Ca2+ stores. Stromal interaction molecule 1
      (STIM1) is the Ca2+ sensor that activates SOCE following ER/SR Ca2+ depletion.
      The EF-hand and the adjacent sterile alpha-motif (EFSAM) domains of STIM1 are
      essential for detecting changes in luminal Ca2+ concentrations. Low ER Ca2+
      levels trigger STIM1 destabilization and oligomerization, culminating in the
      opening of Orai1-composed Ca2+ channels on the plasma membrane. NO-mediated S
      nitrosylation of cysteine thiols regulates myriad protein functions, but its
      effects on the structural mechanisms that regulate SOCE are unclear. Here, we
      demonstrate that S-nitrosylation of Cys49 and Cys56 in STIM1 enhances the
      thermodynamic stability of its luminal domain, resulting in suppressed
      hydrophobic exposure and diminished Ca2+ depletion-dependent oligomerization.
      Using solution NMR spectroscopy, we pinpointed a structural mechanism for STIM1
      stabilization driven by complementary charge interactions between an
      electropositive patch on the core EFSAM domain and the S-nitrosylated
      nonconserved region of STIM1. Finally, using live cells, we found that the
      enhanced luminal domain stability conferred by either Cys49 and Cys56S
      nitrosylation or incorporation of negatively charged residues into the EFSAM
      electropositive patch in the full-length STIM1 context significantly suppresses
      SOCE. Collectively, our results suggest that S-nitrosylation of STIM1 inhibits
      SOCE by interacting with an electropositive patch on the EFSAM core, which
      modulates the thermodynamic stability of the STIM1 luminal domain.

PMID- 29661940
TI  - Disparities for LGBTQ and Gender Nonconforming Adolescents.
AB  - OBJECTIVES: To identify patterns of childhood adversity in a sample of
      adolescents and assess disparities in these experiences for lesbian, gay,
      bisexual, transgender, and questioning adolescents and by level of gender
      nonconformity. METHOD: By using the cross-sectional, statewide, anonymous 2016
      Minnesota Student Survey, 81 885 students were included in the current study
      (50.59% male; mean age = 15.51). Participants were enrolled in grades 9 and 11 in
      a total of 348 schools. RESULTS: Four patterns of childhood adversity were
      identified with sex-stratified latent class analyses (entropy = 0.833 males;
      0.833 females), ranging from relatively low levels of abuse (85.3% males; 80.1%
      females) to polyvictimization (0.84% males; 1.98% females). A regression analysis
      showed that compared with heterosexual adolescents, gay, lesbian, bisexual, and
      questioning adolescents were more likely to be classified into profiles
      characterized by polyvictimization (odds ratio [OR] 1.81-7.53) and psychological
      and/or physical abuse (OR 1.29-3.12), than no or low adversity. Similarly,
      compared with nontransgender adolescents, transgender adolescents were more
      likely to be classified into profiles characterized by patterns of
      polyvictimization (OR 1.49-2.91) and psychological and/or physical abuse (OR 1.23
      1.96). A higher level of gender nonconformity predicted a higher likelihood of
      being classified into each adversity profile compared with the no or low
      adversity profile (OR 1.14-1.45). CONCLUSIONS: Sexual minority adolescents and
      adolescents with high levels of gender nonconformity are vulnerable to experience
      adversity. The disparities for lesbian, gay, bisexual, transgender, and
      questioning adolescents and adolescents with high gender nonconformity highlight
      the variation in patterns of childhood adversity that these youth are at risk of
      experiencing. The findings reveal the need for further research on the benefits
      and harm of screening for childhood adversity by physicians and pediatricians.

PMID- 29661939
TI  - Sexual Orientation and Depressive Symptoms in Adolescents.
AB  - OBJECTIVES: Sexual orientation disparities in adolescent depressive symptoms are
      well established, but reasons for these disparities are less well understood. We
      modeled sexual orientation disparities in depressive symptoms from late
      adolescence into young adulthood and evaluated family satisfaction, peer support,
      cyberbullying victimization, and unmet medical needs as potential mediators.
      METHODS: Data were from waves 2 to 6 of the NEXT Generation Health Study (n =
      2396), a population-based cohort of US adolescents. We used latent growth models
      to examine sexual orientation disparities in depressive symptoms in participants
      aged 17 to 21 years, conduct mediation analyses, and examine sex differences.
      RESULTS: Relative to heterosexual adolescents, sexual minority adolescents (those
      who are attracted to the same or both sexes or are questioning; 6.3% of the
      weighted sample) consistently reported higher depressive symptoms from 11th grade
      to 3 years after high school. Mediation analyses indicated that sexual minority
      adolescents reported lower family satisfaction, greater cyberbullying
      victimization, and increased likelihood of unmet medical needs, all of which were
      associated with higher depressive symptoms. The mediating role of cyberbullying
      victimization was more pronounced among male than female participants.
      CONCLUSIONS: Sexual minority adolescents reported higher depressive symptoms than
      heterosexual adolescents from late adolescence into young adulthood.
      Collectively, low family satisfaction, cyberbullying victimization, and unmet
      medical needs accounted for >45% of differences by sexual orientation. Future
      clinical research is needed to determine if interventions targeting these
      psychosocial and health care-related factors would reduce sexual orientation
      disparities in depressive symptoms and the optimal timing of such interventions.

PMID- 29661938
TI  - Dual functionality of beta-tryptase protomers as both proteases and cofactors in
      the active tetramer.
AB  - Human beta-tryptase, a tetrameric trypsin-like serine protease, is an important
      mediator of the allergic inflammatory responses in asthma. During acute
      hypersensitivity reactions, mast cells degranulate, releasing active tetramer as
      a complex with proteoglycans. Extensive efforts have focused on developing
      therapeutic beta-tryptase inhibitors, but its unique activation mechanism is less
      well-explored. Tryptase is active only after proteolytic removal of the pro
      domain followed by tetramer formation via two distinct symmetry-related
      interfaces. We show that the cleaved I16G mutant cannot tetramerize, likely due
      to impaired insertion of its N terminus into its "activation pocket," indicating
      allosteric linkage at multiple sites on each protomer. We engineered cysteines
      into each of the two distinct interfaces (Y75C for small or I99C for large) to
      assess the activity of each tetramer and disulfide-locked dimer. Using size
      exclusion chromatography and enzymatic assays, we demonstrate that the two large
      tetramer interfaces regulate enzymatic activity, elucidating the importance of
      this protein-protein interaction for allosteric regulation. Notably, the I99C
      large interface dimer is active, even in the absence of heparin. We show that a
      monomeric beta-tryptase mutant (I99C*/Y75A/Y37bA, where C* is cysteinylated Cys
      99) cannot form a dimer or tetramer, yet it is active but only in the presence of
      heparin. Thus heparin both stabilizes the tetramer and allosterically conditions
      the active site. We hypothesize that each beta-tryptase protomer in the tetramer
      has two distinct roles, acting both as a protease and as a cofactor for its
      neighboring protomer, to allosterically regulate enzymatic activity, providing a
      rationale for direct correlation of tetramer stability with proteolytic activity.

PMID- 29661942
TI  - A Closer Look at the Psychosocial Realities of LGBTQ Youth.

PMID- 29661943
TI  - Skills and characteristics of the e-health literate patient.

PMID- 29661941
TI  - Mental Health of Transgender and Gender Nonconforming Youth Compared With Their
      Peers.
AB  - BACKGROUND: Understanding the magnitude of mental health problems, particularly
      life-threatening ones, experienced by transgender and/or gender nonconforming
      (TGNC) youth can lead to improved management of these conditions. METHODS:
      Electronic medical records were used to identify a cohort of 588 transfeminine
      and 745 transmasculine children (3-9 years old) and adolescents (10-17 years old)
      enrolled in integrated health care systems in California and Georgia. Ten male
      and 10 female referent cisgender enrollees were matched to each TGNC individual
      on year of birth, race and/or ethnicity, study site, and membership year of the
      index date (first evidence of gender nonconforming status). Prevalence ratios
      were calculated by dividing the proportion of TGNC individuals with a specific
      mental health diagnosis or diagnostic category by the corresponding proportion in
      each reference group by transfeminine and/or transmasculine status, age group,
      and time period before the index date. RESULTS: Common diagnoses for children and
      adolescents were attention deficit disorders (transfeminine 15%; transmasculine
      16%) and depressive disorders (transfeminine 49%; transmasculine 62%),
      respectively. For all diagnostic categories, prevalence was severalfold higher
      among TGNC youth than in matched reference groups. Prevalence ratios (95%
      confidence intervals [CIs]) for history of self-inflicted injury in adolescents 6
      months before the index date ranged from 18 (95% CI 4.4-82) to 144 (95% CI 36
      1248). The corresponding range for suicidal ideation was 25 (95% CI 14-45) to 54
      (95% CI 18-218). CONCLUSIONS: TGNC youth may present with mental health
      conditions requiring immediate evaluation and implementation of clinical, social,
      and educational gender identity support measures.

PMID- 29661944
TI  - Atrial Fibrillation Burden: Moving Beyond Atrial Fibrillation as a Binary Entity:
      A Scientific Statement From the American Heart Association.
AB  - Our understanding of the risk factors and complications of atrial fibrillation
      (AF) is based mostly on studies that have evaluated AF in a binary fashion
      (present or absent) and have not investigated AF burden. This scientific
      statement discusses the published literature and knowledge gaps related to
      methods of defining and measuring AF burden, the relationship of AF burden to
      cardiovascular and neurological outcomes, and the effect of lifestyle and risk
      factor modification on AF burden. Many studies examine outcomes by AF burden
      classified by AF type (paroxysmal versus nonparoxysmal); however, quantitatively,
      AF burden can be defined by longest duration, number of AF episodes during a
      monitoring period, and the proportion of time an individual is in AF during a
      monitoring period (expressed as a percentage). Current guidelines make identical
      recommendations for anticoagulation regardless of AF pattern or burden; however,
      a review of recent evidence suggests that higher AF burden is associated with
      higher risk of stroke. It is unclear whether the risk increases continuously or
      whether a threshold exists; if a threshold exists, it has not been defined.
      Higher burden of AF is also associated with higher prevalence and incidence of
      heart failure and higher risk of mortality, but not necessarily lower quality of
      life. A structured and comprehensive risk factor management program targeting
      risk factors, weight loss, and maintenance of a healthy weight appears to be
      effective in reducing AF burden. Despite this growing understanding of AF burden,
      research is needed into validation of definitions and measures of AF burden,
      determination of the threshold of AF burden that results in an increased risk of
      stroke that warrants anticoagulation, and discovery of the mechanisms underlying
      the weak temporal correlations of AF and stroke. Moreover, developments in
      monitoring technologies will likely change the landscape of long-term AF
      monitoring and could allow better definition of the significance of changes in AF
      burden over time.

PMID- 29661947
TI  - Return of Oral Anticoagulation in Chronic Stable Coronary Disease.

PMID- 29661948
TI  - Continuing Conundrum of Multiple Arterial Conduits for Coronary Artery Bypass
      Grafting.

PMID- 29661945
TI  - Cigarette Smoking and Incident Heart Failure: Insights From the Jackson Heart
      Study.
AB  - BACKGROUND: Cigarette smoking has been linked with several factors associated
      with cardiac dysfunction. We hypothesized that cigarette smoking is associated
      with left ventricular (LV) structure and function, and incident heart failure
      (HF) hospitalization. METHODS: We investigated 4129 (never smoker n=2884, current
      smoker n=503, and former smoker n=742) black participants (mean age, 54 years;
      63% women) without a history of HF or coronary heart disease at baseline in the
      Jackson Heart Study. We examined the relationships between cigarette smoking and
      LV structure and function by using cardiac magnetic resonance imaging among 1092
      participants, cigarette smoking and brain natriuretic peptide levels among 3325
      participants, and incident HF hospitalization among 3633 participants with
      complete data. RESULTS: After adjustment for confounding factors, current smoking
      was associated with higher mean LV mass index and lower mean LV circumferential
      strain (P<0.05, for both) in comparison with never smoking. Smoking status,
      intensity, and burden were associated with higher mean brain natriuretic peptide
      levels (all P<0.05). Over 8.0 years (7.7-8.0) median follow-up, there were 147
      incident HF hospitalizations. After adjustment for traditional risk factors and
      incident coronary heart disease, current smoking (hazard ratio, 2.82; 95%
      confidence interval, 1.71-4.64), smoking intensity among current smokers (>=20
      cigarettes/d: hazard ratio, 3.48; 95% confidence interval, 1.65-7.32), and
      smoking burden among ever smokers (>=15 pack-years: hazard ratio, 2.06; 95%
      confidence interval, 1.29-3.3) were significantly associated with incident HF
      hospitalization in comparison with never smoking. CONCLUSIONS: In blacks,
      cigarette smoking is an important risk factor for LV hypertrophy, systolic
      dysfunction, and incident HF hospitalization even after adjusting for effects on
      coronary heart disease.

PMID- 29661949
TI  - Getting to Dry.

PMID- 29661950
TI  - Why Don't We Kill 2 Birds with 1 Stone? Less Adverse Cardiac Events and Improved
      Survival With Multiarterial Coronary Artery Bypass Grafting.

PMID- 29661951
TI  - Role of Invasive Functional Assessment in Surgical Revascularization of Coronary
      Artery Disease.
AB  - In patients with stable coronary artery disease, percutaneous coronary
      intervention is associated with improved outcomes if the lesion is deemed
      significant by invasive functional assessment using fractional flow reserve.
      Recent studies have shown that a revascularization strategy using instantaneous
      wave-free ratio is noninferior to fractional flow reserve in patients with
      intermediate-grade stenoses. The decision to perform coronary artery bypass
      grafting surgery is usually based on anatomic assessment of stenosis severity by
      coronary angiography. The data on the role of invasive functional assessment in
      guiding surgical revascularization are limited. In this review, we discuss the
      diagnostic and prognostic significance of invasive functional assessment in
      patients considered for coronary artery bypass grafting. In addition, we
      critically discuss ongoing and future clinical trials on the role of invasive
      functional assessment in surgical revascularization.

PMID- 29661952
TI  - Shifting Landscape for Bundled Payments for Heart Conditions.

PMID- 29661953
TI  - Cardiac Arrest With ST-Segment-Elevation in V1 and V2: Differential Diagnosis.

PMID- 29661954
TI  - Inpatient Echocardiography Use for Common Cardiovascular Conditions.

PMID- 29661955
TI  - Letter by Bulluck and Hausenloy Regarding Article, "Dynamic Edematous Response of
      the Human Heart to Myocardial Infarction: Implications for Assessing Myocardial
      Area at Risk and Salvage".

PMID- 29661956
TI  - Letter by Sacha and Feusette Regarding Article, "Dynamic Edematous Response of
      the Human Heart to Myocardial Infarction: Implications for Assessing Myocardial
      Area at Risk and Salvage".

PMID- 29661957
TI  - Letter by Stiermaier et al Regarding Article, "Dynamic Edematous Response of the
      Human Heart to Myocardial Infarction: Implications for Assessing Myocardial Area
      at Risk and Salvage".

PMID- 29661958
TI  - Response by Fernandez-Jimenez et al to Letters Regarding Article, "Dynamic
      Edematous Response of the Human Heart to Myocardial Infarction: Implications for
      Assessing Myocardial Area at Risk and Salvage".

PMID- 29661959
TI  - Letter by Jin-shan and Xue-bin Regarding Article, "Cardioprotective Role of Tumor
      Necrosis Factor Receptor-Associated Factor 2 by Suppressing Apoptosis and
      Necroptosis".

PMID- 29661960
TI  - Response by Liu to Letter Regarding Article, "Cardioprotective Role of Tumor
      Necrosis Factor Receptor-Associated Factor 2 by Suppressing Apoptosis and
      Necroptosis".

PMID- 29661961
TI  - Letter by Mewton et al Regarding Article, "Validity of Cardiovascular Data From
      Electronic Sources: The Multi-Ethnic Study of Atherosclerosis and HealthLNK".

PMID- 29661962
TI  - Response by Ahmad et al to Letter Regarding Article, "Validity of Cardiovascular
      Data From Electronic Sources: The Multi-Ethnic Study of Atherosclerosis and
      HealthLNK".

PMID- 29661963
TI  - Obesity suppresses tumor attributable PSA, affecting risk categorization.
AB  - Obesity is linked with more aggressive prostate cancer and higher rates of
      disease recurrence post treatment. It is unclear if this is due to specific tumor
      promoting effects of obesity or diagnostic bias. Patients undergoing
      prostatectomy were categorized according to their body mass index (BMI). Expected
      prostate-specific antigen (PSA) levels were calculated for each patient based on
      tumor characteristics. The effect of obesity on the accuracy of pre-treatment
      risk categorization was determined, and mediation analysis was used to identify
      the contribution of biologic vs non-biologic mechanisms to the observed increased
      risk of biochemical recurrence. Residual tumor-promoting effects were estimated
      in a survival model controlling for diagnostic error. The following results were
      obtained. The analysis included 1587 patients. Despite similar rates of adverse
      pathological features at prostatectomy, biochemical recurrence rates were
      significantly higher in very obese patients, which persisted after adjustment for
      stage, grade and PSA. Tumor volume however correlated significantly with BMI (P =
      0.004), and the difference in predicted and observed 'tumor-attributable' PSA
      (Delta-PSA) in very obese patients was greater than three times higher than that
      of healthy patients (P = 0.0067). Regression analysis indicated that the effect
      of BMI on tumor volume was fully mediated indirectly by its effect on PSA.
      Inclusion of this diagnostic error as a covariate in the survival analysis
      attenuated the effect of BMI on recurrence. In conclusion, being very obese
      suppresses tumor-associated PSA resulting in a diagnostic bias that is
      responsible for errors in risk classification, and potentially contributes to a
      delay in initial presentation.

PMID- 29661964
TI  - Refinement of Spatial Receptive Fields in the Developing Mouse Lateral Geniculate
      Nucleus Is Coordinated with Excitatory and Inhibitory Remodeling.
AB  - Receptive field properties of individual visual neurons are dictated by the
      precise patterns of synaptic connections they receive, including the arrangement
      of inputs in visual space and features such as polarity (On vs Off). The inputs
      from the retina to the lateral geniculate nucleus (LGN) in the mouse undergo
      significant refinement during development. However, it is unknown how this
      refinement corresponds to the establishment of functional visual response
      properties. Here we conducted in vivo and in vitro recordings in the mouse LGN,
      beginning just after natural eye opening, to determine how receptive fields
      develop as excitatory and feedforward inhibitory retinal afferents refine.
      Experiments used both male and female subjects. For in vivo assessment of
      receptive fields, we performed multisite extracellular recordings in awake mice.
      Spatial receptive fields at eye-opening were >2 times larger than in adulthood,
      and decreased in size over the subsequent week. This topographic refinement was
      accompanied by other spatial changes, such as a decrease in spot size preference
      and an increase in surround suppression. Notably, the degree of specificity in
      terms of On/Off and sustained/transient responses appeared to be established
      already at eye opening and did not change. We performed in vitro recordings of
      the synaptic responses evoked by optic tract stimulation across the same time
      period. These recordings revealed a pairing of decreased excitatory and increased
      feedforward inhibitory convergence, providing a potential mechanism to explain
      the spatial receptive field refinement.SIGNIFICANCE STATEMENT The development of
      precise patterns of retinogeniculate connectivity has been a powerful model
      system for understanding the mechanisms underlying the activity-dependent
      refinement of sensory systems. Here we link the maturation of spatial receptive
      field properties in the lateral geniculate nucleus (LGN) to the remodeling of
      retinal and inhibitory feedforward convergence onto LGN neurons. These findings
      should thus provide a starting point for testing the cell type-specific
      plasticity mechanisms that lead to refinement of different excitatory and
      inhibitory inputs, and for determining the effect of these mechanisms on the
      establishment of mature receptive fields in the LGN.

PMID- 29661965
TI  - Neural Activity in Ventral Medial Prefrontal Cortex Is Modulated More Before
      Approach Than Avoidance During Reinforced and Extinction Trial Blocks.
AB  - Ventromedial prefrontal cortex (vmPFC) is thought to provide regulatory control
      over Pavlovian fear responses and has recently been implicated in appetitive
      approach behavior, but much less is known about its role in contexts in which
      appetitive and aversive outcomes can be obtained and avoided, respectively. To
      address this issue, we recorded from single neurons in vmPFC while male rats
      performed our combined approach and avoidance task under reinforced and non
      reinforced (extinction) conditions. Surprisingly, we found that cues predicting
      reward modulated cell firing in vmPFC more often and more robustly than cues
      preceding avoidable shock; in addition, firing of vmPFC neurons was both response
      (press or no-press) and outcome (reinforced or extinction) selective. These
      results suggest a complex role for vmPFC in regulating behavior and support its
      role in appetitive contexts during both reinforced and non-reinforced
      conditions.SIGNIFICANCE STATEMENT Selecting context-appropriate behaviors to gain
      reward or avoid punishment is critical for survival. Although the role of
      ventromedial prefrontal cortex (vmPFC) in mediating fear responses is well
      established, vmPFC has also been implicated in the regulation of reward-guided
      approach and extinction. Many studies have used indirect methods and simple
      behavioral procedures to study vmPFC, which leaves the literature incomplete. We
      recorded vmFPC neural activity during a complex cue-driven combined approach and
      avoidance task and during extinction. Surprisingly, we found very little vmPFC
      modulation to cues predicting avoidable shock, whereas cues predicting reward
      approach robustly modulated vmPFC firing in a response- and outcome-selective
      manner. This suggests a more complex role for vmPFC than current theories
      suggest, specifically regarding context-specific behavioral optimization.

PMID- 29661966
TI  - Pallidal Deep-Brain Stimulation Disrupts Pallidal Beta Oscillations and Coherence
      with Primary Motor Cortex in Parkinson's Disease.
AB  - In Parkinson's disease (PD), subthalamic nucleus beta band oscillations are
      decreased by therapeutic deep-brain stimulation (DBS) and this has been proposed
      as important to the mechanism of therapy. The globus pallidus is a common
      alternative target for PD with similar motor benefits as subthalamic DBS, but
      effects of pallidal stimulation in PD are not well studied, and effects of
      pallidal DBS on cortical function in PD are unknown. Here, in 20 PD and 14
      isolated dystonia human patients of both genders undergoing pallidal DBS lead
      implantation, we recorded local field potentials from the globus pallidus and in
      a subset of these, recorded simultaneous sensorimotor cortex ECoG potentials. PD
      patients had elevated resting pallidal low beta band (13-20 Hz) power compared
      with dystonia patients, whereas dystonia patients had elevated resting pallidal
      theta band (4-8 Hz) power compared with PD. We show that this results in disease
      specific patterns of interaction between the pallidum and motor cortex: PD
      patients demonstrated relatively elevated phase coherence with the motor cortex
      in the beta band and this was reduced by therapeutic pallidal DBS. Dystonia
      patients had greater theta band phase coherence. Our results support the
      hypothesis that specific motor phenomenology observed in movement disorders are
      associated with elevated network oscillations in specific frequency bands, and
      that DBS in movement disorders acts in general by disrupting elevated
      synchronization between basal ganglia output and motor cortex.SIGNIFICANCE
      STATEMENT Perturbations in synchronized oscillatory activity in brain networks
      are increasingly recognized as important features in movement disorders. The
      globus pallidus is a commonly used target for deep-brain stimulation (DBS) in
      Parkinson's disease (PD), however, the effects of pallidal DBS on basal ganglia
      and cortical oscillations are unknown. Using invasive intraoperative recordings
      in patients with PD and isolated dystonia, we found disease-specific patterns of
      elevated oscillatory synchronization within the pallidum and in coherence between
      pallidum and motor cortex. Therapeutic pallidal DBS in PD suppresses these
      elevated synchronizations, reducing the influence of diseased basal ganglia on
      cortical physiology. We propose a general mechanism for DBS therapy in movement
      disorders: functional disconnection of basal ganglia output and motor cortex by
      coherence suppression.

PMID- 29661968
TI  - Correction: Oral pharmacological chaperone migalastat compared with enzyme
      replacement therapy in Fabry disease: 18-month results from the randomised phase
      III ATTRACT study.

PMID- 29661967
TI  - Detachment of Chain-Forming Neuroblasts by Fyn-Mediated Control of cell-cell
      Adhesion in the Postnatal Brain.
AB  - In the rodent olfactory system, neuroblasts produced in the ventricular
      subventricular zone of the postnatal brain migrate tangentially in chain-like
      cell aggregates toward the olfactory bulb (OB) through the rostral migratory
      stream (RMS). After reaching the OB, the chains are dissociated and the
      neuroblasts migrate individually and radially toward their final destination. The
      cellular and molecular mechanisms controlling cell-cell adhesion during this
      detachment remain unclear. Here we report that Fyn, a nonreceptor tyrosine
      kinase, regulates the detachment of neuroblasts from chains in the male and
      female mouse OB. By performing chemical screening and in vivo loss-of-function
      and gain-of-function experiments, we found that Fyn promotes somal disengagement
      from the chains and is involved in neuronal migration from the RMS into the
      granule cell layer of the OB. Fyn knockdown or Dab1 (disabled-1) deficiency
      caused p120-catenin to accumulate and adherens junction-like structures to be
      sustained at the contact sites between neuroblasts. Moreover, a Fyn and N
      cadherin double-knockdown experiment indicated that Fyn regulates the N-cadherin
      mediated cell adhesion between neuroblasts. These results suggest that the Fyn
      mediated control of cell-cell adhesion is critical for the detachment of chain
      forming neuroblasts in the postnatal OB.SIGNIFICANCE STATEMENT In the postnatal
      brain, newly born neurons (neuroblasts) migrate in chain-like cell aggregates
      toward their destination, where they are dissociated into individual cells and
      mature. The cellular and molecular mechanisms controlling the detachment of
      neuroblasts from chains are not understood. Here we show that Fyn, a nonreceptor
      tyrosine kinase, promotes the somal detachment of neuroblasts from chains, and
      that this regulation is critical for the efficient migration of neuroblasts to
      their destination. We further show that Fyn and Dab1 (disabled-1) decrease the
      cell-cell adhesion between chain-forming neuroblasts, which involves adherens
      junction-like structures. Our results suggest that Fyn-mediated regulation of the
      cell-cell adhesion of neuroblasts is critical for their detachment from chains in
      the postnatal brain.

PMID- 29661969
TI  - Mutations in plasmalemma vesicle-associated protein cause severe syndromic
      protein-losing enteropathy.
AB  - BACKGROUND: Protein-losing enteropathy (PLE) is characterised by gastrointestinal
      protein leakage due to loss of mucosal integrity or lymphatic abnormalities. PLE
      can manifest as congenital diarrhoea and should be differentiated from other
      congenital diarrhoeal disorders. Primary PLEs are genetically heterogeneous and
      the underlying genetic defects are currently emerging. OBJECTIVES: We report an
      infant with fatal PLE for whom we aimed to uncover the underlying pathogenic
      mutation. METHODS: We performed whole exome sequencing (WES) for the index
      patient. Variants were classified based on the American College of Medical
      Genetics and Genomics guidelines. WES results and our detailed clinical
      description of the patient were compared with the literature. RESULTS: We
      discovered a novel homozygous stop mutation (c.988C>T, p.Q330*) in the
      Plasmalemma Vesicle-Associated Protein (PLVAP) gene in a newborn with fatal PLE,
      facial dysmorphism, and renal, ocular and cardiac anomalies. The Q330* mutation
      is predicted to result in complete loss of PLVAP protein expression leading to
      deletion of the diaphragms of endothelial fenestrae, resulting in plasma protein
      extravasation and PLE. Recently, another single homozygous stop mutation in PLVAP
      causing lethal PLE in an infant was reported. CONCLUSIONS: Our findings validate
      PLVAP mutations as a cause of syndromic PLE. Prenatal anomalies, severe PLE and
      syndromic features may guide the diagnosis of this rare disease.

PMID- 29661970
TI  - Consensus for genes to be included on cancer panel tests offered by UK genetics
      services: guidelines of the UK Cancer Genetics Group.
AB  - Genetic testing for hereditary cancer predisposition has evolved rapidly in
      recent years with the discovery of new genes, but there is much debate over the
      clinical utility of testing genes for which there are currently limited data
      regarding the degree of associated cancer risk. To address the discrepancies that
      have arisen in the provision of these tests across the UK, the UK Cancer Genetics
      Group facilitated a 1-day workshop with representation from the majority of
      National Health Service (NHS) clinical genetics services. Using a preworkshop
      survey followed by focused discussion of genes without prior majority agreement
      for inclusion, we achieved consensus for panels of cancer genes with sufficient
      evidence for clinical utility, to be adopted by all NHS genetics services. To
      support consistency in the delivery of these tests and advice given to families
      across the country, we also developed management proposals for individuals who
      are found to have pathogenic mutations in these genes. However, we fully
      acknowledge that the decision regarding what test is most appropriate for an
      individual family rests with the clinician, and will depend on factors including
      specific phenotypic features and the family structure.

PMID- 29661971
TI  - CM-Score: a validated scoring system to predict CDKN2A germline mutations in
      melanoma families from Northern Europe.
AB  - BACKGROUND: Several factors have been reported that influence the probability of
      a germline CDKN2A mutation in a melanoma family. Our goal was to create a scoring
      system to estimate this probability, based on a set of clinical features present
      in the patient and his or her family. METHODS: Five clinical features and their
      association with CDKN2A mutations were investigated in a training cohort of 1227
      Dutch melanoma families (13.7% with CDKN2A mutation) using multivariate logistic
      regression. Predefined features included number of family members with melanoma
      and with multiple primary melanomas, median age at diagnosis and presence of
      pancreatic cancer or upper airway cancer in a family member. Based on these five
      features, a scoring system (CDKN2A Mutation(CM)-Score) was developed and
      subsequently validated in a combined Swedish and Dutch familial melanoma cohort
      (n=421 families; 9.0% with CDKN2A mutation). RESULTS: All five features were
      significantly associated (p<0.05) with a CDKN2A mutation. At a CM-Score of 16 out
      of 49 possible points, the threshold of 10% mutation probability is approximated
      (9.9%; 95% CI 9.8 to 10.1). This probability further increased to >90% for
      families with >=36 points. A CM-Score under 16 points was associated with a low
      mutation probability (<=4%). CM-Score performed well in both the training cohort
      (area under the curve (AUC) 0.89; 95% CI 0.86 to 0.92) and the external
      validation cohort (AUC 0.94; 95% CI 0.90 to 0.98). CONCLUSION: We developed a
      practical scoring system to predict CDKN2A mutation status among melanoma-prone
      families. We suggest that CDKN2A analysis should be recommended to families with
      a CM-Score of >=16 points.

PMID- 29661972
TI  - Gravitational-wave astronomy: delivering on the promises.
AB  - Now that LIGO and Virgo have begun to detect gravitational-wave events with
      regularity, the field of gravitational-wave astronomy is beginning to realize its
      promise. Binary black holes and, very recently, binary neutron stars have been
      observed, and we are already learning much from them. The future, with improved
      sensitivity, more detectors and detectors like LISA in different frequency bands,
      has even more promise to open a completely hidden side of the Universe to our
      exploration.This article is part of a discussion meeting issue 'The promises of
      gravitational-wave astronomy'.

PMID- 29661973
TI  - Quasi-monolithic mirror suspensions in ground-based gravitational-wave detectors:
      an overview and look to the future.
AB  - At the commencement of a new era in astrophysics, with added information from
      direct detections of gravitational-wave (GW) signals, this paper is a testament
      to the quasi-monolithic suspensions of the test masses of the GW detectors that
      have enabled the opening of a new window on the universe. The quasi-monolithic
      suspensions are the final stages in the seismic isolation of the test masses in
      GW detectors, and are specifically designed to introduce as little thermal noise
      as possible. The history of the development of the fused-silica quasi-monolithic
      suspensions, which have been so essential for the first detections of GWs, is
      outlined and a glimpse into the status of research towards quasi-monolithic
      suspensions made of sapphire and silicon is given.This article is part of a
      discussion meeting issue 'The promises of gravitational-wave astronomy'.

PMID- 29661974
TI  - Development of mirror coatings for gravitational-wave detectors.
AB  - Gravitational waves are detected by measuring length changes between mirrors in
      the arms of kilometre-long Michelson interferometers. Brownian thermal noise
      arising from thermal vibrations of the mirrors can limit the sensitivity to
      distance changes between the mirrors, and, therefore, the ability to measure
      gravitational-wave signals. Thermal noise arising from the highly reflective
      mirror coatings will limit the sensitivity both of current detectors (when they
      reach design performance) and of planned future detectors. Therefore, the
      development of coatings with low thermal noise, which at the same time meet
      strict optical requirements, is of great importance. This article gives an
      overview of the current status of coatings and of the different approaches for
      coating improvement.This article is part of a discussion meeting issue 'The
      promises of gravitational-wave astronomy'.

PMID- 29661975
TI  - Gravitational waves from neutron stars and asteroseismology.
AB  - Neutron stars are born in the supernova explosion of massive stars. Neutron stars
      rotate as stably as atomic clocks and possess densities exceeding that of atomic
      nuclei and magnetic fields millions to billions of times stronger than those
      created in laboratories on the Earth. The physical properties of neutron stars
      are determined by many areas of fundamental physics, and detection of
      gravitational waves can provide invaluable insights into our understanding of
      these areas. Here, we describe some of the physics and astrophysics of neutron
      stars and how traditional electromagnetic wave observations provide clues to the
      sorts of gravitational waves we expect from these stars. We pay particular
      attention to neutron star fluid oscillations, examining their impact on
      electromagnetic and gravitational wave observations when these stars are in a
      wide binary or isolated system, then during binary inspiral right before merger,
      and finally at times soon after merger.This article is part of a discussion
      meeting issue 'The promises of gravitational-wave astronomy'.

PMID- 29661976
TI  - Characterizing transient noise in the LIGO detectors.
AB  - Data from the LIGO detectors typically contain many non-Gaussian noise transients
      which arise due to instrumental and environmental conditions. These non-Gaussian
      transients can be an issue for the modelled and unmodelled transient
      gravitational-wave searches, as they can mask or mimic a true signal. Data
      quality can change quite rapidly, making it imperative to track and find new
      sources of transient noise so that data are minimally contaminated. Several
      examples of transient noise and the tools used to track them are presented. These
      instances serve to highlight the diverse range of noise sources present at the
      LIGO detectors during their second observing run.This article is part of a
      discussion meeting issue 'The promises of gravitational-wave astronomy'.

PMID- 29661977
TI  - Gravitational wave detection using laser interferometry beyond the standard
      quantum limit.
AB  - Interferometric gravitational wave detectors (such as advanced LIGO) employ high
      power solid-state lasers to maximize their detection sensitivity and hence their
      reach into the universe. These sophisticated light sources are ultra-stabilized
      with regard to output power, emission frequency and beam geometry; this is
      crucial to obtain low detector noise. However, even when all laser noise is
      reduced as far as technically possible, unavoidable quantum noise of the laser
      still remains. This is a consequence of the Heisenberg Uncertainty Principle, the
      basis of quantum mechanics: in this case, it is fundamentally impossible to
      simultaneously reduce both the phase noise and the amplitude noise of a laser to
      arbitrarily low levels. This fact manifests in the detector noise budget as two
      distinct noise sources-photon shot noise and quantum radiation pressure noise
      which together form a lower boundary for current-day gravitational wave detector
      sensitivities, the standard quantum limit of interferometry. To overcome this
      limit, various techniques are being proposed, among them different uses of non
      classical light and alternative interferometer topologies. This article explains
      how quantum noise enters and manifests in an interferometric gravitational wave
      detector, and gives an overview of some of the schemes proposed to overcome this
      seemingly fundamental limitation, all aimed at the goal of higher gravitational
      wave event detection rates.This article is part of a discussion meeting issue
      'The promises of gravitational-wave astronomy'.

PMID- 29661979
TI  - Microelectromechanical system gravimeters as a new tool for gravity imaging.
AB  - A microelectromechanical system (MEMS) gravimeter has been manufactured with a
      sensitivity of 40 ppb in an integration time of 1 s. This sensor has been used to
      measure the Earth tides: the elastic deformation of the globe due to tidal
      forces. No such measurement has been demonstrated before now with a MEMS
      gravimeter. Since this measurement, the gravimeter has been miniaturized and
      tested in the field. Measurements of the free-air and Bouguer effects have been
      demonstrated by monitoring the change in gravitational acceleration measured
      while going up and down a lift shaft of 20.7 m, and up and down a local hill of
      275 m. These tests demonstrate that the device has the potential to be a useful
      field-portable instrument. The development of an even smaller device is underway,
      with a total package size similar to that of a smartphone.This article is part of
      a discussion meeting issue 'The promises of gravitational-wave astronomy'.

PMID- 29661980
TI  - The prospects of pulsar timing with new-generation radio telescopes and the
      Square Kilometre Array.
AB  - Pulsars are highly magnetized and rapidly rotating neutron stars. As they spin,
      the lighthouse-like beam of radio emission from their magnetic poles sweeps
      across the Earth with a regularity approaching that of the most precise clocks
      known. This precision combined with the extreme environments in which they are
      found, often in compact orbits with other neutron stars and white dwarfs, makes
      them excellent tools for studying gravity. Present and near-future pulsar
      surveys, especially those using the new generation of telescopes, will find more
      extreme binary systems and pulsars that are more precise 'clocks'. These
      telescopes will also greatly improve the precision to which we can measure the
      arrival times of the pulses. The Square Kilometre Array will revolutionize pulsar
      searches and timing precision. The increased number of sources will reveal rare
      sources, including possibly a pulsar-black hole binary, which can provide the
      most stringent tests of strong-field gravity. The improved timing precision will
      reveal new phenomena and also allow us to make a detection of gravitational waves
      in the nanohertz frequency regime. It is here where we expect to see the
      signature of the binary black holes that are formed as galaxies merge throughout
      cosmological history.This article is part of a discussion meeting issue 'The
      promises of gravitational-wave astronomy'.

PMID- 29661978
TI  - Control of cell behaviour through nanovibrational stimulation: nanokicking.
AB  - Mechanical signals are ubiquitous in our everyday life and the process of
      converting these mechanical signals into a biological signalling response is
      known as mechanotransduction. Our understanding of mechanotransduction, and its
      contribution to vital cellular responses, is a rapidly expanding field of
      research involving complex processes that are still not clearly understood. The
      use of mechanical vibration as a stimulus of mechanotransduction, including
      variation of frequency and amplitude, allows an alternative method to control
      specific cell behaviour without chemical stimulation (e.g. growth factors).
      Chemical-independent control of cell behaviour could be highly advantageous for
      fields including drug discovery and clinical tissue engineering. In this review,
      a novel technique is described based on nanoscale sinusoidal vibration. Using
      finite-element analysis in conjunction with laser interferometry, techniques that
      are used within the field of gravitational wave detection, optimization of
      apparatus design and calibration of vibration application have been performed. We
      further discuss the application of nanovibrational stimulation, or 'nanokicking',
      to eukaryotic and prokaryotic cells including the differentiation of mesenchymal
      stem cells towards an osteoblast cell lineage. Mechanotransductive mechanisms are
      discussed including mediation through the Rho-A kinase signalling pathway.
      Optimization of this technique was first performed in two-dimensional culture
      using a simple vibration platform with an optimal frequency and amplitude of 1
      kHz and 22 nm. A novel bioreactor was developed to scale up cell production, with
      recent research demonstrating that mesenchymal stem cell differentiation can be
      efficiently triggered in soft gel constructs. This important step provides first
      evidence that clinically relevant (three-dimensional) volumes of osteoblasts can
      be produced for the purpose of bone grafting, without complex scaffolds and/or
      chemical induction. Initial findings have shown that nanovibrational stimulation
      can also reduce biofilm formation in a number of clinically relevant bacteria.
      This demonstrates additional utility of the bioreactor to investigate
      mechanotransduction in other fields of research.This article is part of a
      discussion meeting issue 'The promises of gravitational-wave astronomy'.

PMID- 29661981
TI  - High-energy astrophysics and the search for sources of gravitational waves.
AB  - The dawn of the gravitational-wave (GW) era has sparked a greatly renewed
      interest into possible links between sources of high-energy radiation and GWs.
      The most luminous high-energy sources-gamma-ray bursts (GRBs)-have long been
      considered as very likely sources of GWs, particularly from short-duration GRBs,
      which are thought to originate from the merger of two compact objects such as
      binary neutron stars and a neutron star-black hole binary. In this paper, we
      discuss: (i) the high-energy emission from short-duration GRBs; (ii) what other
      sources of high-energy radiation may be observed from binary mergers; and (iii)
      how searches for high-energy electromagnetic counterparts to GW events are
      performed with current space facilities. While current high-energy facilities,
      such as Swift and Fermi, play a crucial role in the search for electromagnetic
      counterparts, new space missions will greatly enhance our capabilities for joint
      observations. We discuss why such facilities, which incorporate new technology
      that enables very wide-field X-ray imaging, are required if we are to truly
      exploit the multi-messenger era.This article is part of a discussion meeting
      issue 'The promises of gravitational-wave astronomy'.

PMID- 29661982
TI  - The promises of gravitational-wave astronomy.

PMID- 29661983
TI  - The evolution of CpG density and lifespan in conserved primate and mammalian
      promoters.
AB  - Gene promoters are evolutionarily conserved across holozoans and enriched in CpG
      sites, the target for DNA methylation. As animals age, the epigenetic pattern of
      DNA methylation degrades, with highly methylated CpG sites gradually becoming
      demethylated while CpG islands increase in methylation. Across vertebrates, aging
      is a trait that varies among species. We used this variation to determine whether
      promoter CpG density correlates with species' maximum lifespan. Human promoter
      sequences were used to identify conserved regions in 131 mammals and a subset of
      28 primate genomes. We identified approximately 1000 gene promoters (5% of the
      total), that significantly correlated CpG density with lifespan. The correlations
      were performed via the phylogenetic least squares method to account for trait
      similarity by common descent using phylogenetic branch lengths. Gene set
      enrichment analysis revealed no significantly enriched pathways or processes,
      consistent with the hypothesis that aging is not under positive selection.
      However, within both mammals and primates, 95% of the promoters showed a positive
      correlation between increasing CpG density and species lifespan, and two thirds
      were shared between the primate subset and mammalian datasets. Thus, these genes
      may require greater buffering capacity against age-related dysregulation of DNA
      methylation in longer-lived species.

PMID- 29661984
TI  - Unrepaired DNA damage in macrophages causes elevation of particulate matter-
      induced airway inflammatory response.
AB  - The inflammatory cascade can be initiated with the recognition of damaged DNA.
      Macrophages play an essential role in particulate matter (PM)-induced airway
      inflammation. In this study, we aim to explore the PM induced DNA damage response
      of macrophages and its function in airway inflammation. The DNA damage response
      and inflammatory response were assessed using bone marrow-derived macrophages
      following PM treatment and mouse model instilled intratracheally with PM. We
      found that PM induced significant DNA damage both in vitro and in vivo and
      simultaneously triggered a rapid DNA damage response, represented by nuclear RPA,
      53BP1 and gammaH2AX foci formation. Genetic ablation or chemical inhibition of
      the DNA damage response sensor amplified the production of cytokines including
      Cxcl1, Cxcl2 and Ifn-gamma after PM stimulation in bone marrow-derived
      macrophages. Similar to that seen in vitro, mice with myeloid-specific deletion
      of RAD50 showed higher levels of airway inflammation in response to the PM
      challenge, suggesting a protective role of DNA damage sensor during inflammation.
      These data demonstrate that PM exposure induces DNA damage and activation of DNA
      damage response sensor MRN complex in macrophages. Disruption of MRN complex lead
      to persistent, unrepaired DNA damage that causes elevated inflammatory response.

PMID- 29661985
TI  - A net-shaped multicellular formation facilitates the maturation of hPSC-derived
      cardiomyocytes through mechanical and electrophysiological stimuli.
AB  - The use of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs)
      is limited in drug discovery and cardiac disease mechanism studies due to cell
      immaturity. Although many approaches have been reported to improve the maturation
      of hiPSC-CMs, the elucidation of the process of maturation is crucial. We applied
      a small-molecule-based differentiation method to generate cardiomyocytes (CMs)
      with multiple aggregation forms. The motion analysis revealed significant
      physical differences in the differently shaped CMs, and the net-shaped CMs had
      larger motion amplitudes and faster velocities than the sheet-shaped CMs. The net
      shaped CMs displayed accelerated maturation at the transcriptional level and were
      more similar to CMs with a prolonged culture time (30 days) than to sheet-d15.
      Ion channel genes and gap junction proteins were up-regulated in net-shaped CMs,
      indicating that robust contraction was coupled with enhanced ion channel and
      connexin expression. The net-shaped CMs also displayed improved myofibril
      ultrastructure under transmission electron microscopy. In conclusion, different
      multicellular hPSC-CM structures, such as the net-shaped pattern, are formed
      using the conditioned induction method, providing a useful tool to improve
      cardiac maturation.

PMID- 29661986
TI  - Maxillary sinus mucocele with orbital complications.
AB  - INTRODUCTION: Maxillary sinus mucocele is an unusual clinic entity (incidence of
      3-10%), represented by mucous secretion lined by respiratory stratified
      pavemented epithelium and its origin is mainly secondary to infections,
      inflammations, surgery, trauma or neoplasia. CASE REPORT: We present a case of
      maxillary sinus mucocele. Subject of the study is a 74 aged patient referring
      positive anamnesis for nasal cavity surgery. His symptoms appeared six months ago
      and he complainted vertical ocular diplopia and ocular tension sensation, without
      rhinologic complaints. Oculistic examination confirmed an isolated left inferior
      rectus palsy, and CT showed mucous secretion occupying left maxillary sinus, with
      bone erosion to the orbital floor until orbital muscles. MRI is the gold standard
      for differential diagnosis with neoplastic lesions but the patient refused to
      perform this radio-diagnostic exam. He underwent to Endoscopic sinus surgery,
      consisting in middle meatal antrostomy and removal of the mucocele. Four months
      later the endoscopic follow-up showed regular maxillary cavity and regular ocular
      motility. CONCLUSION: In our opinion the rebuilding of the eroded bone is not
      mandatory if the integrity of the maxillary upper wall mucosa is respected, and
      antrostomy with drainage allows to recover ocular and paranasal sinus function.
      KEY WORDS:, Diplopia, Endoscopic sinus surgery.

PMID- 29661987
TI  - Review of the Latest Percutaneous Devices in Critical Limb Ischemia.
AB  - Critical limb ischemia (CLI) is a terminal stage of peripheral arterial disease
      that, in the absence of intervention, may lead to lower extremity amputation or
      death. Endovascular interventions have become a first-line approach to the
      management of CLI and have advanced considerably within the past decade. This
      review summarizes the types of percutaneous devices and the techniques that are
      available for the management of CLI and the data supporting their use. These
      include devices that establish and maintain vessel patency, including
      percutaneous transluminal angioplasty, drug-coated balloons, bare metal stents,
      drug-eluting stents, bioresorbable vascular scaffolds, and atherectomy; devices
      that provide protection from embolization; and, cell-based therapies.
      Additionally, ongoing trials with important implications for the field are
      discussed.

PMID- 29661988
TI  - The Effect of Axon Resealing on Retrograde Neuronal Death after Spinal Cord
      Injury in Lamprey.
AB  - Failure of axon regeneration in the central nervous system (CNS) of mammals is
      due to both extrinsic inhibitory factors and to neuron-intrinsic factors. The
      importance of intrinsic factors is illustrated in the sea lamprey by the 18 pairs
      of large, individually identified reticulospinal (RS) neurons, whose axons are
      located in the same spinal cord tracts but vary greatly in their ability to
      regenerate after spinal cord transection (TX). The neurons that are bad
      regenerators also undergo very delayed apoptosis, signaled early by activation of
      caspases. We noticed that the neurons with a low probability of axon regeneration
      tend to be larger than the good regenerators. We postulate that the poorly
      regenerating larger neurons have larger caliber axons, which reseal more slowly,
      allowing more prolonged entry of toxic signals (e.g., Ca++) into the axon at the
      injury site. To test this hypothesis, we used a dye-exclusion assay, applying
      membrane-impermeable dyes to the cut ends of spinal cords at progressively longer
      post-TX intervals. Axons belonging to the very small neurons (not individually
      identified) of the medial inferior RS nucleus resealed within 15 min post-TX.
      Almost 75% of axons belonging to the medium-sized identified RS neurons resealed
      within 3 h. At this time, only 36% of the largest axons had resealed, often
      taking more than 24 h to exclude the dye. There was an inverse relationship
      between an RS neuron's size and the probability that its axon would regenerate (r
      = -0.92) and that the neuron would undergo delayed apoptosis, as indicated by
      staining with a fluorescently labeled inhibitor of caspases (FLICA; r = 0.73).
      The artificial acceleration of resealing with polyethylene glycol (PEG) reduced
      retrograde neuronal apoptosis by 69.5% at 2 weeks after spinal cord injury (SCI),
      suggesting that axon resealing is a critical determinant of cell survival. Ca++
      free Ringer's solution with EGTA prolonged the sealing time and increased
      apoptotic signaling, suggesting that factors other than Ca++ diffusion into the
      injured tip contribute to retrograde death signaling. A longer distance of the
      lesion from the cell body reduced apoptotic signaling independent of the axon
      sealing time.

PMID- 29661989
TI  - Preconcentration and Determination of Perfluoroalkyl Substances (PFASs) in Water
      Samples by Bamboo Charcoal-Based Solid-Phase Extraction Prior to Liquid
      Chromatography-Tandem Mass Spectrometry.
AB  - In this work, bamboo charcoal was used as solid-phase extraction adsorbent for
      the enrichment of six perfluoroalkyl acids (PFAAs) in environmental water samples
      before liquid chromatography-tandem mass spectrometry analysis. The specific
      porous structure, high specific surface area, high porosity, and stability of
      bamboo charcoal were characterized. Several experimental parameters which
      considerably affect extraction efficiency were investigated and optimized in
      detail. The experimental data exhibited low limits of detection (LODs) (0.01-1.15
      ng/L), wide linear range (2-3 orders of magnitude and R >= 0.993) within the
      concentration range of 0.1-1000 ng/L, and good repeatability (2.7-5.0%, n = 5
      intraday and 4.8-8.3%, n = 5 interday) and reproducibility (5.3-8.0%, n = 3).
      Bamboo charcoal was successfully used for the enrichment and determination of
      PFAAs in real environmental water samples. The bamboo charcoal-based solid-phase
      extraction coupled with liquid chromatography-tandem mass spectrometry analysis
      possessed great potential in the determination of trace PFAA levels in
      environmental water samples.

PMID- 29661990
TI  - Effect of Traffic Noise and Relaxations Sounds on Pedestrian Walking Speed.
AB  - Exposure to noise in everyday urban life is considered to be an environmental
      stressor. A specific outcome of reactions to environmental stress is a fast pace
      of life that also includes a faster pedestrian walking speed. The present study
      examined the effect of listening to annoying acoustical stimuli (traffic noise)
      compared with relaxation sounds (forest birdsong) on walking speed in a real
      outdoor urban environment. The participants (N = 83) walked along an urban route
      of 1.8 km. They listened to either traffic noise or forest birdsong, or they
      walked without listening to any acoustical stimuli in the control condition. The
      results showed that participants listening to traffic noise walked significantly
      faster on the route than both the participants listening to forest birdsong
      sounds and the participants in the control condition. Participants who listened
      to forest birdsong walked slightly slower than those under control conditions;
      however, this difference was not significant. Analysis of the walk experience
      showed that participants who listened to forest birdsong during the walk liked
      the route more than those who listened to traffic sounds. The study demonstrated
      that exposure to traffic noise led to an immediate increase in walking speed. It
      was also shown that exposure to noise may influence participants' perception of
      an environment. The same environment may be more liked in the absence of noise or
      in the presence of relaxation sounds. The study also documented the positive
      effect of listening to various kinds of relaxation sounds while walking in an
      outdoor environment with traffic noise.

PMID- 29661991
TI  - Information to Improve Public Perceptions of the Food and Drug Administration
      (FDA's) Tobacco Regulatory Role.
AB  - While the Food and Drug Administration (FDA) has had regulatory authority over
      tobacco products since 2009, public awareness of this authority remains limited.
      This research examines several broad types of information about FDA tobacco
      regulatory mission that may improve the perceptions of FDA as a tobacco
      regulator. Using Amazon Mechanical Turk, 1766 adults, smokers and non-smokers,
      were randomly assigned to view a statement about FDA regulatory authority that
      varied three information types in a 2 * 2 * 2 between subjects experimental
      design: (1) FDA's roles in regulating tobacco (yes/no); (2) The scientific basis
      of regulations (yes/no); and (3) A potential protective function of regulations
      (yes/no). Using factorial ANOVA, we estimated the main and interactive effects of
      all three types of information and of smoking status on the perceptions of FDA.
      Participants that were exposed to information on FDA roles reported higher FDA
      credibility and a greater perceived knowledge of FDA than those who did not.
      Exposure to information about the scientific basis of regulations led to more
      negative views of the tobacco industry. Participants who learned of the FDA's
      commitment to protecting the public reported higher FDA credibility and more
      positive attitudes toward regulations than those who did not learn of this
      commitment. We observed no significant interaction effects. The findings suggest
      that providing information about the regulatory roles and protective
      characterization of the FDA's tobacco regulatory mission positively influence
      public perceptions of FDA and tobacco regulations.

PMID- 29661992
TI  - Controlled Synthesis of Cu and Cu2O NPs and Incorporation of Octahedral Cu2O NPs
      in Cellulose II Films.
AB  - In this study, Cu and Cu2O nanoparticles (NPs) were synthesized through chemical
      reduction of soluble copper-chelating ligand complexes using formaldehyde as a
      reducing agent. The influence of various chelating ligands, such as
      ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid
      (DTPA), and a surface-active derivative of DTPA (C12-DTPA), as well as
      surfactants (i.e., hexadecyltrimethylammonium bromide (CTAB),
      dodecyltrimethylammonium chloride (DoTAC), sodium dodecyl sulfate (SDS), and
      dimethyldodecylamine-N-oxide (DDAO)), on morphology and the composition of
      produced NPs was investigated. In the absence of surfactants, spherical copper
      particles with polycrystalline structure could be obtained. X-ray diffraction
      (XRD) analysis revealed that, in the presence of EDTA, the synthesized NPs are
      mainly composed of Cu with a crystallite size on the order of 35 nm, while with
      DTPA and C12-DTPA, Cu2O is also present in the NPs as a minority phase. The
      addition of ionic surfactants to the copper-EDTA complex solution before
      reduction resulted in smaller spherical particles, mainly composed of Cu.
      However, when DDAO was added, pure Cu2O nano-octahedrons were formed, as verified
      by high-resolution scanning electron microscopy (HR-SEM) and XRD. Furthermore, a
      hybrid material could be successfully prepared by mixing the octahedral Cu2O NPs
      with cellulose dissolved in a LiOH/urea solvent system, followed by spin-coating
      on silica wafers. It is expected that this simple and scalable route to prepare
      hybrid materials could be applied to a variety of possible applications.

PMID- 29661993
TI  - The Cellular Mechanisms that Ensure an Efficient Secretion in Streptomyces.
AB  - Gram-positive soil bacteria included in the genus Streptomyces produce a large
      variety of secondary metabolites in addition to extracellular hydrolytic enzymes.
      From the industrial and commercial viewpoints, the S. lividans strain has
      generated greater interest as a host bacterium for the overproduction of
      homologous and heterologous hydrolytic enzymes as an industrial application,
      which has considerably increased scientific interest in the characterization of
      secretion routes in this bacterium. This review will focus on the secretion
      machinery in S. lividans.

PMID- 29661994
TI  - Baseline Apparent Diffusion Coefficient as a Predictor of Response to Liver
      Directed Therapies in Hepatocellular Carcinoma.
AB  - Predicting outcomes in patients with hepatocellular carcinoma (HCC) who undergo
      locoregional therapies remains a substantial clinical challenge. The purpose of
      this study was to investigate pre-procedure diffusion weighted magnetic resonance
      imaging (DW-MRI) as an imaging biomarker for tumoral response to therapy for
      patients with HCC undergoing drug eluting embolic (DEE) chemoembolization and
      radioembolization. A retrospective review of HCC patients who underwent DEE
      chemoembolization or radioembolization was performed. Of the 58 patients who
      comprised the study population, 32 underwent DEE chemoembolization and 26
      underwent radioembolization. There was no significant difference in median
      apparent diffusion coefficient (ADC) values across the two treatment groups (1.01
      * 10-3 mm2/s, P = 0.25). The immediate objective response (OR) rate was 71%
      (40/56). Tumors with high ADC values were found to have a higher probability of
      OR within 90 days (odds ratio 4.4, P = 0.03). Moreover, index lesion specific
      progression free survival (PFS) was greater for high ADC tumors, independent of
      conventional predictors of treatment response (hazard ratio 0.44, P = 0.01). Low
      ADC was associated with poorer PFS (P = 0.02). Pre-procedure ADC < 1.01 * 10-3
      mm2/s is an independent predictor of poorer immediate OR and index lesion
      specific PFS in patients with HCC undergoing DEE chemoembolization or
      radioembolization.

PMID- 29661995
TI  - Greater Glycaemic Response to an Oral Glucose Load in Healthy, Lean, Active and
      Young Chinese Adults Compared to Matched Caucasians.
AB  - There are ethnic differences recorded in glycaemic response and rates of type 2
      diabetes mellitus (DM) between Chinese and Caucasian populations. Whether these
      differences are evident in matched healthy, lean, active, young adults is
      unclear. This study compares the postprandial glycaemic response of a group of
      Chinese participants (n = 49) with a group of similar Caucasians, (n = 48) aged
      23.8 (+/-4.35 years), body mass index (BMI) 22.7 (+/-2.6) kg/m2, healthy (free
      from non-communicable disease), and lean (body fat % 23.28% (+/-5.04)).
      Participants undertook an oral glucose tolerance test to identify any significant
      differences in postprandial blood glucose response. Body fat percentage, body
      mass, age, physical activity, baseline glucose and HbA1c did not significantly
      differ between groups. Data from food frequency questionnaires indicated that the
      Chinese participants consumed less starchy foods, candy and "other" sweets and
      sugary drinks, and more rice than the Caucasians (all p <= 0.001), but not a
      greater overall intake of carbohydrates or any other macronutrient (all p >
      0.05). The two groups' postprandial blood glucose responses and 2-h incremental
      area under the curve values (iAUC)-156.67 (74.12) mmol/L 120 min for Caucasians
      versus 214.03 (77.49) mmol/L 120 min for Chinese-indicate significant differences
      (p = 0.003 and p < 0.001 respectively) between groups. Findings suggest that the
      difference between the two groups' iAUC values do not relate to obvious lifestyle
      factors. The Chinese group were eating the least sugary and starchy food but had
      the highest iAUC. It is argued that the Chinese group in this investigation have
      the most favourable BMI, body fat percentage, and body mass, yet "poorest"
      glycaemic response.

PMID- 29661996
TI  - Iron Is the Active Site in Nickel/Iron Water Oxidation Electrocatalysts.
AB  - Efficient catalysis of the oxygen-evolution half-reaction (OER) is a pivotal
      requirement for the development of practical solar-driven water splitting
      devices. Heterogeneous OER electrocatalysts containing first-row transition metal
      oxides and hydroxides have attracted considerable recent interest, owing in part
      to the high abundance and low cost of starting materials. Among the best
      performing OER electrocatalysts are mixed Fe/Ni layered double hydroxides (LDH).
      A review of the available experimental data leads to the conclusion that iron is
      the active site for [NiFe]-LDH-catalyzed alkaline water oxidation.

PMID- 29661997
TI  - Implementation of Safe-by-Design for Nanomaterial Development and Safe
      Innovation: Why We Need a Comprehensive Approach.
AB  - Manufactured nanomaterials (MNMs) are regarded as key components of innovations
      in various fields with high potential impact (e.g., energy generation and
      storage, electronics, photonics, diagnostics, theranostics, or drug delivery
      agents). Widespread use of MNMs raises concerns about their safety for humans and
      the environment, possibly limiting the impact of the nanotechnology-based
      innovation. The development of safe MNMs and nanoproducts has to result in a safe
      as well as functional material or product. Its safe use, and disposal at the end
      of its life cycle must be taken into account too. However, not all MNMs are
      similarly useful for all applications, some might bear a higher hazard potential
      than others, and use scenarios could lead to different exposure probabilities. To
      improve both safety and efficacy of nanotechnology, we think that a new proactive
      approach is necessary, based on pre-regulatory safety assessment and dialogue
      between stakeholders. On the basis of the work carried out in different European
      Union (EU) initiatives, developing and integrating MNMs Safe-by-Design and
      Trusted Environments (NANoREG, ProSafe, and NanoReg2), we present our point of
      view here. This concept, when fully developed, will allow for cost effective
      industrial innovation, and an exchange of key information between regulators and
      innovators. Regulators are thus informed about incoming innovations in good time,
      supporting a proactive regulatory action. The final goal is to contribute to the
      nanotechnology governance, having faster, cheaper, effective, and safer nano
      products on the market.

PMID- 29661998
TI  - Association and Expression of Virulence from Plasmids of the Group B Strain in
      Pseudomonas syringae pv. eriobotryae.
AB  - Pseudomonas syringae pv. eriobotryae causes serious stem canker in loquat
      (Eriobotrya japonica) trees. This study was conducted to determine whether
      plasmids are involved with its virulence. The strain NAE89, which belonged to the
      B group, harbored two plasmids at approximately 6.2 and 50 Mdal that caused stem
      canker and halo leaf spots on loquat plants. Following digestion with BamHI and
      ligation into the BamHI cloning site of the broad range host cosmid pLAFR3, four
      DNA fragments at 3.8, 6.6, 12.3, and 22.8 kb were generated. Although the plasmid
      encoded virulence gene psvA was undigested with the BamHI, the halo leaf spot
      gene may be adjacent to the psvA gene was digested. A pLAFR3 cosmid clone was
      introduced into the non-pathogenic PE0 and NAE89-1 strains by triparental matings
      and the pathogenicity was recovered. As a result, the pLAFR3 cosmid clone was
      introduced into the largest size DNA fragment of 22.8 kb and determined to be the
      causal agent of canker on the stem of the loquat. This study revealed that the
      psvA gene, previously found in the 50 Mdal plasmid, was also observed in the 22.8
      kb DNA fragment.

PMID- 29661999
TI  - Performance Analysis of BDS Medium-Long Baseline RTK Positioning Using an
      Empirical Troposphere Model.
AB  - For GPS medium-long baseline real-time kinematic (RTK) positioning, the
      troposphere parameter is introduced along with coordinates, and the model is ill
      conditioned due to its strong correlation with the height parameter. For BeiDou
      Navigation Satellite System (BDS), additional difficulties occur due to its
      special satellite constellation. In fact, relative zenith troposphere delay
      (RZTD) derived from high-precision empirical zenith troposphere models can be
      introduced. Thus, the model strength can be improved, which is also called the
      RZTD-constrained RTK model. In this contribution, we first analyze the factors
      affecting the precision of BDS medium-long baseline RTK; thereafter, 15 baselines
      ranging from 38 km to 167 km in different troposphere conditions are processed to
      assess the performance of RZTD-constrained RTK. Results show that the troposphere
      parameter is difficult to distinguish from the height component, even with long
      time filtering for BDS-only RTK. Due to the lack of variation in geometry for the
      BDS geostationary Earth orbit satellite, the long convergence time of ambiguity
      parameters may reduce the height precision of GPS/BDS-combined RTK in the initial
      period. When the RZTD-constrained model was used in BDS and GPS/BDS-combined
      situations compared with the traditional RTK, the standard deviation of the
      height component for the fixed solution was reduced by 52.4% and 34.0%,
      respectively.

PMID- 29662000
TI  - Habitual Flavonoid Intake from Fruit and Vegetables during Adolescence and Serum
      Lipid Levels in Early Adulthood: A Prospective Analysis.
AB  - Flavonoids have been implicated in the prevention of cardiovascular diseases
      (CVD). In a prospective approach, we investigated whether habitual flavonoid
      intake from fruit, vegetables and juices (FlavFVJ) during adolescence is
      associated with adult levels of serum lipids, one of the main CVD risk factors.
      This analysis included healthy participants from the Dortmund Nutritional and
      Anthropometric Longitudinally Designed (DONALD) study, who had provided a fasting
      blood sample in adulthood (aged 18-39 years), data on FlavFVJ intake during
      adolescence (females: 9-15 years, males: 10-16 years)-estimated either from
      multiple 3-day weighed dietary records (n = 257), or from validated biomarker
      hippuric acid (uHA) excretion from multiple 24-h urine samples (n = 233)-together
      with information on relevant covariates. In multivariable linear regression
      analyses, a higher FlavFVJ intake during adolescence was independently associated
      with higher serum high-density lipoprotein cholesterol (HDL-C) levels among males
      (Ptrend = 0.038); however, the inclusion of adult waist circumference attenuated
      this association (Ptrend = 0.053). FlavFVJ was not associated with triglycerides
      (TG), total cholesterol (TC) or low-density lipoprotein cholesterol (LDL-C; all
      Ptrend >= 0.1), nor was uHA excretion with any serum lipid outcome among males
      (all Ptrend >= 0.5). Neither FlavFVJ intake nor uHA excretion was associated with
      serum lipids among women (all Ptrend >= 0.1). However, a higher flavonoid intake
      from fruit and vegetables was independently related to lower LDL-C levels (Ptrend
      = 0.021), while a higher intake from juices was associated with higher LDL-C
      levels (Ptrend = 0.016) among females. In conclusion, a higher flavonoid intake
      from fruit, vegetables and/or juices during adolescence may be linked to
      cholesterol levels in early adulthood in a sex- and food source-specific manner.

PMID- 29662001
TI  - Association between Ambient Temperatures and Mental Disorder Hospitalizations in
      a Subtropical City: A Time-Series Study of Hong Kong Special Administrative
      Region.
AB  - Background: Mental disorders have been found to be positively associated with
      temperature in cool to cold climatic regions but the association in warmer
      regions is unclear. This study presented the short-term association between
      temperatures and mental disorder hospitalizations in a subtropical city with a
      mean annual temperature over 21  degrees C. Methods: Using Poisson-generalized
      additive models and distributed-lagged nonlinear models, daily mental disorder
      hospitalizations between 2002 and 2011 in Hong Kong were regressed on daily mean
      temperature, relative humidity, and air pollutants, adjusted for seasonal trend,
      long-term trend, day-of-week, and holiday. Analyses were stratified by disease
      class, gender and age-group. Results: 44,600 admissions were included in the
      analysis. Temperature was positively associated with overall mental-disorder
      hospitalizations (cumulative relative risk at 28  degrees C vs. 19.4  degrees C
      (interquartile range, lag 0-2 days) = 1.09 (95% confidence interval 1.03, 1.15)),
      with the strongest effect among the elderly (>=75 years old). Transient mental
      disorders due to conditions classified elsewhere and episodic mood disorders also
      showed strong positive associations with temperature. Conclusion: This study
      found a positive temperature-mental-disorder admissions association in a warm
      subtropical region and the association was most prominent among older people.
      With the dual effect of global warming and an aging population, targeted
      strategies should be designed to lower the disease burden.

PMID- 29662002
TI  - Carotenoid Lutein Selectively Inhibits Breast Cancer Cell Growth and Potentiates
      the Effect of Chemotherapeutic Agents through ROS-Mediated Mechanisms.
AB  - Increasing evidence suggests that dietary carotenoids may reduce the risk of
      breast cancer. However, anti-breast cancer effects of carotenoids have been
      controversial, albeit understudied. Here, we investigated the effects of specific
      carotenoids on a wide range of breast cancer cell lines, and found that among
      several carotenoids (including beta-carotene, lutein, and astaxanthin), lutein
      significantly inhibits breast cancer cell growth by inducing cell-cycle arrest
      and caspase-independent cell death, but it has little effect on the growth of
      primary mammary epithelial cells (PmECs). Moreover, lutein-mediated growth
      inhibition of breast cancer cells is quantitatively similar to that induced by
      chemotherapeutic taxanes, paclitaxel and docetaxel, and exposure to lutein plus
      taxanes additively inhibits breast cancer cell growth. Analysis of mechanisms
      showed that lutein treatment significantly increases the intracellular reactive
      oxygen species (ROS) production in triple-negative breast cancer (TNBC) cells,
      but not in normal PmECs. Lutein-induced growth inhibition is also attenuated by
      the radical oxygen scavenger N-acetyl cysteine, suggesting a role for ROS
      generation in the growth inhibitory effect of lutein on TNBC cells. Additionally,
      we found that the p53 signaling pathway is activated and HSP60 levels are
      increased by lutein treatment, which may contribute partly to the induction of
      growth inhibition in TNBC cells. Our findings show that lutein promotes growth
      inhibition of breast cancer cells through increased cell type-specific ROS
      generation and alternation of several signaling pathways. Dietary lutein
      supplementation may be a promising alternative and/or adjunct therapeutic
      candidate against breast cancer.

PMID- 29662004
TI  - UV Light-Assisted Synthesis of Highly Efficient Pd-Based Catalyst over NiO for
      Hydrogenation of o-Chloronitrobenzene.
AB  - Supported Pd-based catalyst over active nickel oxide (NiO) was repared using the
      impregnation method companying with UV-light irradiation. Moreover, the catalytic
      performance of the obtained Pd-based catalysts was evaluated towards the
      hydrogenation of o-chloronitrobenzene (o-CNB). Observations indicate that the as
      prepared UV-irradiated Pd/NiO catalyst with a mole fraction 0.2% (0.2%Pd/NiO) has
      higher activity and selectivity in the o-CNB hydrogenation. Especially, UV-light
      irradiation played a positive role in the improvement of catalytic activity of
      0.2%Pd/NiO catalyst, exhibiting an excess 11-fold activity superiority in
      contrast with non-UV-irradiated 0.2%Pd/NiO catalyst. In addition, it was
      investigated that effects of varied factors (i.e., reaction time, temperature, o
      CNB/Pd ratio, Pd loading, hydrogen pressure) on the selective hydrogenation of
      omicron-CNB catalyzed by UV-irradiated 0.2%Pd/NiO catalyst. Under the reaction
      conditions of 60  degrees C, 0.5 h, 1 MPa H2 pressure, 100% conversion of o-CNB,
      and 81.1% o-CAN selectivity were obtained, even at high molar ratio (8000:1) of o
      CNB to Pd.

PMID- 29662005
TI  - Complexes of CO2 with the Azoles: Tetrel Bonds, Hydrogen Bonds and Other
      Secondary Interactions.
AB  - Ab initio MP2/aug'-cc-pVTZ calculations have been performed to investigate the
      complexes of CO2 with the azoles pyrrole, pyrazole, imidazole, 1,2,3- and 1,2,4
      triazole, tetrazole and pentazole. Three types of complexes have been found on
      the CO2:azole potential surfaces. These include ten complexes stabilized by
      tetrel bonds that have the azole molecule in the symmetry plane of the complex;
      seven tetrel-bonded complexes in which the CO2 molecule is perpendicular to the
      symmetry plane; and four hydrogen-bonded complexes. Eight of the planar complexes
      are stabilized by Nx...C tetrel bonds and by a secondary interaction involving an
      adjacent Ny-H bond and an O atom of CO2. The seven perpendicular CO2:azole
      complexes form between CO2 and two adjacent N atoms of the ring, both of which
      are electron-pair donors. In three of the four hydrogen-bonded complexes, the
      proton-donor Nz-H bond of the ring is bonded to two C-H bonds, thereby precluding
      the planar and perpendicular complexes. The fourth hydrogen-bonded complex forms
      with the strongest acid pentazole. Binding energies, charge-transfer energies and
      changes in CO2 stretching and bending frequencies upon complex formation provide
      consistent descriptions of these complexes. Coupling constants across tetrel
      bonds are negligibly small, but 2hJ(Ny-C) across Nz-H...C hydrogen bonds are
      larger and increase as the number of N atoms in the ring increases.

PMID- 29662006
TI  - Hyperinsulinemia Promotes Esophageal Cancer Development in a Surgically-Induced
      Duodeno-Esophageal Reflux Murine Model.
AB  - Hyperinsulinemia could have a role in the growing incidence of esophageal
      adenocarcinoma (EAC) and its pre-cancerous lesion, Barrett's Esophagus, a
      possible consequence of Gastro-Esophageal Reflux Disease. Obesity is known to
      mediate esophageal carcinogenesis through different mechanisms including insulin
      resistance leading to hyperinsulinemia, which may mediate cancer progression via
      the insulin/insulin-like growth factor axis. We used the hyperinsulinemic non
      obese FVB/N (Friend leukemia virus B strain) MKR (muscle (M)-IGF1R-lysine (K)
      arginine (R) mouse model to evaluate the exclusive role of hyperinsulinemia in
      the pathogenesis of EAC related to duodeno-esophageal reflux. FVB/N wild-type
      (WT) and MKR mice underwent jejunum-esophageal anastomosis side-to end with the
      exclusion of the stomach. Thirty weeks after surgery, the esophagus was processed
      for histological, immunological and insulin/Insulin-like growth factor 1 (IGF1)
      signal transduction analyses. Most of the WT mice (63.1%) developed dysplasia,
      whereas most of the MKR mice (74.3%) developed squamous cell and adenosquamous
      carcinomas, both expressing Human Epidermal growth factor receptor 2 (HER2).
      Hyperinsulinemia significantly increased esophageal cancer incidence in the
      presence of duodenal-reflux. Insulin receptor (IR) and IGF1 receptor (IGF1R) were
      overexpressed in the hyperinsulinemic condition. IGF1R, through ERK1/2 mitogenic
      pattern activation, seems to be involved in cancer onset. Hyperinsulinemia
      induced IGF1R and HER2 up-regulation could also increase the possibility of
      forming of IGF1R/HER2 heterodimers to support cell
      growth/proliferation/progression in esophageal carcinogenesis.

PMID- 29662003
TI  - PPAR Agonists and Metabolic Syndrome: An Established Role?
AB  - Therapeutic approaches to metabolic syndrome (MetS) are numerous and may target
      lipoproteins, blood pressure or anthropometric indices. Peroxisome proliferator
      activated receptors (PPARs) are involved in the metabolic regulation of lipid and
      lipoprotein levels, i.e., triglycerides (TGs), blood glucose, and abdominal
      adiposity. PPARs may be classified into the alpha, beta/delta and gamma subtypes.
      The PPAR-alpha agonists, mainly fibrates (including newer molecules such as
      pemafibrate) and omega-3 fatty acids, are powerful TG-lowering agents. They
      mainly affect TG catabolism and, particularly with fibrates, raise the levels of
      high-density lipoprotein cholesterol (HDL-C). PPAR-gamma agonists, mainly
      glitazones, show a smaller activity on TGs but are powerful glucose-lowering
      agents. Newer PPAR-alpha/delta agonists, e.g., elafibranor, have been designed to
      achieve single drugs with TG-lowering and HDL-C-raising effects, in addition to
      the insulin-sensitizing and antihyperglycemic effects of glitazones. They also
      hold promise for the treatment of non-alcoholic fatty liver disease (NAFLD) which
      is closely associated with the MetS. The PPAR system thus offers an important
      hope in the management of atherogenic dyslipidemias, although concerns regarding
      potential adverse events such as the rise of plasma creatinine, gallstone
      formation, drug-drug interactions (i.e., gemfibrozil) and myopathy should also be
      acknowledged.

PMID- 29662008
TI  - An Embedded Sensory System for Worker Safety: Prototype Development and
      Evaluation.
AB  - At a construction site, workers mainly rely on two senses, which are sight and
      sound, in order to perceive their physical surroundings. However, they are often
      hindered by the nature of most construction sites, which are usually dynamic,
      loud, and complicated. To overcome these challenges, this research explored a
      method using an embedded sensory system that might offer construction workers an
      artificial sensing ability to better perceive their surroundings. This study
      identified three parameters (i.e., intensity, signal length, and delay between
      consecutive pulses) needed for tactile-based signals for the construction workers
      to communicate quickly. We developed a prototype system based on these
      parameters, conducted experimental studies to quantify and validate the
      sensitivity of the parameters for quick communication, and analyzed test data to
      reveal what was added by this method in order to perceive information from the
      tactile signals. The findings disclosed that the parameters of tactile-based
      signals and their distinguishable ranges could be perceived in a short amount of
      time (i.e., a fraction of a second). Further experimentation demonstrated the
      capability of the identified unit signals combined with a signal mapping
      technique to effectively deliver simple information to individuals and offer an
      additional sense of awareness to the surroundings. The findings of this study
      could serve as a basis for future research in exploring advanced tactile-based
      messages to overcome challenges in environments for which communication is a
      struggle.

PMID- 29662009
TI  - Design and Investigation of Optical Properties of N-(Rhodamine-B)-Lactam
      Ethylenediamine (RhB-EDA) Fluorescent Probe.
AB  - This study presents chemical modification of a Rhodamine B (RhB) sensor probe by
      ethylenediamine (EDA), and investigation of its spectral as well as sensor
      properties to the various metals. The synthesised N-(Rhodamine-B)-lactam
      ethylenediamine (RhB-EDA) fluorescent probe shows interesting optical sensor
      properties, and high sensitivity and selectivity to Ag+ ions among all the tested
      metal ions (K+, Mg2+, Cu2+, Ni2+, Fe2+, Pb2+, Na+, Mn2+, Li+, Al3+, Co2+, Hg2+,
      Sr2+, Ca2+, Ag+, Cd2+ and Zn2+), while the well-known Rhodamine B (RhB)
      fluorescent probe shows much less sensitivity to Ag+ ions, but high sensitivity
      to Fe2+ ions. The novel fluorescent sensor probe RhB-EDA has the capabilities to
      sense Ag+ ions up to uM ranges by using the fluorescence quenching approach. The
      probe displayed a dynamic response to Ag+ in the range of 0.43 * 10-3-10-6 M with
      a detection limit of 0.1 MUM. The sensing system of an RhB-EDA novel fluorescent
      probe was optimised according to the spectral properties, effect of pH and
      buffer, photostability, incubation time, sensitivity, and selectivity. Since all
      the spectral and sensing properties were tested in green aqueous media, although
      many other similar sensor systems rely on organic solvent solutions, the RhB-EDA
      sensing probe may be a good candidate for measuring Ag+ ions in real-life
      applications.

PMID- 29662007
TI  - MicroRNAs as Potential Regulators of Glutathione Peroxidases Expression and Their
      Role in Obesity and Related Pathologies.
AB  - Glutathione peroxidases (GPxs) belong to the eight-member family of
      phylogenetically related enzymes with different cellular localization, but
      distinct antioxidant function. Several GPxs are important selenoproteins.
      Dysregulated GPx expression is connected with severe pathologies, including
      obesity and diabetes. We performed a comprehensive bioinformatic analysis using
      the programs miRDB, miRanda, TargetScan, and Diana in the search for hypothetical
      microRNAs targeting 3'untranslated regions (3'UTR) of GPxs. We cross-referenced
      the literature for possible intersections between our results and available
      reports on identified microRNAs, with a special focus on the microRNAs related to
      oxidative stress, obesity, and related pathologies. We identified many microRNAs
      with an association with oxidative stress and obesity as putative regulators of
      GPxs. In particular, miR-185-5p was predicted by a larger number of programs to
      target six GPxs and thus could play the role as their master regulator. This
      microRNA was altered by selenium deficiency and can play a role as a feedback
      control of selenoproteins' expression. Through the bioinformatics analysis we
      revealed the potential connection of microRNAs, GPxs, obesity, and other redox
      imbalance related diseases.

PMID- 29662011
TI  - Using Ontologies for the Online Recognition of Activities of Daily Living.
AB  - The recognition of activities of daily living is an important research area of
      interest in recent years. The process of activity recognition aims to recognize
      the actions of one or more people in a smart environment, in which a set of
      sensors has been deployed. Usually, all the events produced during each activity
      are taken into account to develop the classification models. However, the instant
      in which an activity started is unknown in a real environment. Therefore, only
      the most recent events are usually used. In this paper, we use statistics to
      determine the most appropriate length of that interval for each type of activity.
      In addition, we use ontologies to automatically generate features that serve as
      the input for the supervised learning algorithms that produce the classification
      model. The features are formed by combining the entities in the ontology, such as
      concepts and properties. The results obtained show a significant increase in the
      accuracy of the classification models generated with respect to the classical
      approach, in which only the state of the sensors is taken into account. Moreover,
      the results obtained in a simulation of a real environment under an event-based
      segmentation also show an improvement in most activities.

PMID- 29662010
TI  - Metabolic Features of Multiple Myeloma.
AB  - Cancer is known for its cellular changes contributing to tumour growth and cell
      proliferation. As part of these changes, metabolic rearrangements are identified
      in several cancers, including multiple myeloma (MM), which is a condition whereby
      malignant plasma cells accumulate in the bone marrow (BM). These metabolic
      changes consist of generation, inhibition and accumulation of metabolites and
      metabolic shifts in MM cells. Changes in the BM micro-environment could be the
      reason for such adjustments. Enhancement of glycolysis and glutaminolysis is
      found in MM cells compared to healthy cells. Metabolites and enzymes can be
      upregulated or downregulated and play a crucial role in drug resistance.
      Therefore, this review will focus on changes in glucose and glutamine metabolism
      linked with the emergence of drug resistance. Moreover, metabolites do not only
      affect other metabolic components to benefit cancer development; they also
      interfere with transcription factors involved in proliferation and apoptotic
      regulation.

PMID- 29662012
TI  - Influence of Highly Accessible Urban Food Environment on Weight Management: A
      Qualitative Study in Seoul.
AB  - We explored the characteristics of the food environment and its influence on
      weight management in Seoul, Korea. Photo elicitation interviews were conducted
      with 73 participants who took three photographs per topic related to their food
      environment and discussed these photographs in groups. Through thematic analysis,
      we identified four themes concerning participants' perceptions of the food
      environment and weight management: (1) "convenience comes first," (2) "tempting
      food environment," (3) "alcohol and anju," and (4) "burden of individual effort
      to manage weight." A systematic change toward an environment supportive of
      healthy eating and weight management is recommended.

PMID- 29662013
TI  - Rolling Bearing Fault Diagnosis Based on an Improved HTT Transform.
AB  - When rolling bearing failure occurs, vibration signals generally contain
      different signal components, such as impulsive fault feature signals, background
      noise and harmonic interference signals. One of the most challenging aspects of
      rolling bearing fault diagnosis is how to inhibit noise and harmonic interference
      signals, while enhancing impulsive fault feature signals. This paper presents a
      novel bearing fault diagnosis method, namely an improved Hilbert time-time (IHTT)
      transform, by combining a Hilbert time-time (HTT) transform with principal
      component analysis (PCA). Firstly, the HTT transform was performed on vibration
      signals to derive a HTT transform matrix. Then, PCA was employed to de-noise the
      HTT transform matrix in order to improve the robustness of the HTT transform.
      Finally, the diagonal time series of the de-noised HTT transform matrix was
      extracted as the enhanced impulsive fault feature signal and the contained fault
      characteristic information was identified through further analyses of amplitude
      and envelope spectrums. Both simulated and experimental analyses validated the
      superiority of the presented method for detecting bearing failures.

PMID- 29662015
TI  - Structural Characterization and Interaction with RCA120 of a Highly Sulfated
      Keratan Sulfate from Blue Shark (Prionace glauca) Cartilage.
AB  - As an important glycosaminoglycan, keratan sulfate (KS) mainly exists in corneal
      and cartilage, possessing various biological activities. In this study, we
      purified KS from blue shark (Prionace glauca) cartilage and prepared KS
      oligosaccharides (KSO) through keratanase II-catalyzed hydrolysis. The structures
      of KS and KSO were characterized using multi-dimensional nuclear magnetic
      resonance (NMR) spectra and liquid chromatography-mass spectrometry (LC-MS).
      Shark cartilage KS was highly sulfated and modified with ~2.69% N
      acetylneuraminic acid (NeuAc) through alpha(2,3)-linked to galactose.
      Additionally, KS exhibited binding affinity to Ricinus communis agglutinin I
      (RCA120) in a concentration-dependent manner, a highly toxic lectin from beans of
      the castor plant. Furthermore, KSO from dp2 to dp8 bound to RCA120 in the
      increasing trend while the binding affinity of dp8 was superior to
      polysaccharide. These results define novel structural features for KS from
      Prionace glauca cartilage and demonstrate the potential application on ricin
      antidote exploitation.

PMID- 29662014
TI  - Interferon Independent Non-Canonical STAT Activation and Virus Induced
      Inflammation.
AB  - Interferons (IFNs) are a group of secreted proteins that play critical roles in
      antiviral immunity, antitumor activity, activation of cytotoxic T cells, and
      modulation of host immune responses. IFNs are cytokines, and bind receptors on
      cell surfaces to trigger signal transduction. The major signaling pathway
      activated by IFNs is the JAK/STAT (Janus kinase/signal transducer and activator
      of transcription) pathway, a complex pathway involved in both viral and host
      survival strategies. On the one hand, viruses have evolved strategies to escape
      from antiviral host defenses evoked by IFN-activated JAK/STAT signaling. On the
      other hand, viruses have also evolved to exploit the JAK/STAT pathway to evoke
      activation of certain STATs that somehow promote viral pathogenesis. In this
      review, recent progress in our understanding of the virus-induced IFN-independent
      STAT signaling and its potential roles in viral induced inflammation and
      pathogenesis are summarized in detail, and perspectives are provided.

PMID- 29662016
TI  - Persistent Borrelia Infection in Patients with Ongoing Symptoms of Lyme Disease.
AB  - INTRODUCTION: Lyme disease is a tickborne illness that generates controversy
      among medical providers and researchers. One of the key topics of debate is the
      existence of persistent infection with the Lyme spirochete, Borreliaburgdorferi,
      in patients who have been treated with recommended doses of antibiotics yet
      remain symptomatic. Persistent spirochetal infection despite antibiotic therapy
      has recently been demonstrated in non-human primates. We present evidence of
      persistent Borrelia infection despite antibiotic therapy in patients with ongoing
      Lyme disease symptoms. METHODS: In this pilot study, culture of body fluids and
      tissues was performed in a randomly selected group of 12 patients with persistent
      Lyme disease symptoms who had been treated or who were being treated with
      antibiotics. Cultures were also performed on a group of ten control subjects
      without Lyme disease. The cultures were subjected to corroborative microscopic,
      histopathological and molecular testing for Borrelia organisms in four
      independent laboratories in a blinded manner. RESULTS: Motile spirochetes
      identified histopathologically as Borrelia were detected in culture specimens,
      and these spirochetes were genetically identified as Borreliaburgdorferi by three
      distinct polymerase chain reaction (PCR)-based approaches. Spirochetes identified
      as Borrelia burgdorferi were cultured from the blood of seven subjects, from the
      genital secretions of ten subjects, and from a skin lesion of one subject.
      Cultures from control subjects without Lyme disease were negative for Borrelia
      using these methods. CONCLUSIONS: Using multiple corroborative detection methods,
      we showed that patients with persistent Lyme disease symptoms may have ongoing
      spirochetal infection despite antibiotic treatment, similar to findings in non
      human primates. The optimal treatment for persistent Borrelia infection remains
      to be determined.

PMID- 29662017
TI  - Use of Unpalatable Forages by Ruminants: The Influence of Experience with the
      Biophysical and Social Environment.
AB  - Unpalatable forage resources (low nutrient density, potentially toxic
      metabolites) are widespread and represent a challenge for ruminant nutrition,
      health, and welfare. Our objective was to synthesize the role of biophysical and
      social experience on the use of unpalatable forages by ruminants, and highlight
      derived behavioural solutions for the well-being of soils, plants, and animals.
      Environmental experiences early in life modulate gene expression and promote
      learning, which alters morpho-physiological and psychological mechanisms that
      modify behavioural responses and change food and habitat selection. In this
      process, ruminants can become better adapted to the habitat where they are
      reared. Moreover, experiential learning provides flexibility in diet selection,
      which is critical for changing foraging environments. Learned associations
      between unpalatable and palatable foods, if ingested in appropriate amounts,
      sequence, and close temporal association, induce the development of preference
      for the former type of food. In this way, a more uniform use of resources can be
      achieved from the landscape level down to the individual plant, with the
      associated benefits to ecosystem integrity and stability. Ruminants can also
      learn the medicinal benefits of ingesting foods with toxins (e.g., condensed
      tannins and saponins with antiparasitic properties). This knowledge on
      behavioural processes can be translated into behavioural applications that
      provide low-cost solutions to many challenges that producers face in managing
      sustainable livestock production systems.

PMID- 29662018
TI  - Rheological and Mechanical Properties of Thermoresponsive Methylcellulose/Calcium
      Phosphate-Based Injectable Bone Substitutes.
AB  - In this study, a novel injectable bone substitute (IBS) was prepared by
      incorporating a bioceramic powder in a polymeric solution comprising of
      methylcellulose (MC), gelatin and citric acid. Methylcellulose was utilized as
      the polymeric matrix due to its thermoresponsive properties and biocompatibility.
      2.5 wt % gelatin and 3 wt % citric acid were added to the MC to adjust the
      rheological properties of the prepared IBS. Then, 0, 20, 30 and 50 wt % of the
      bioceramic component comprising tetracalcium phosphate/hydroxyapatite (TTCP/HA),
      dicalcium phosphate dehydrate (DCPD) and calcium sulfate dehydrate (CSD) were
      added into the prepared polymeric component. The prepared IBS samples had a
      chewing gum-like consistency. IBS samples were investigated in terms of their
      chemical structure, rheological characteristics, and mechanical properties. After
      that, in vitro degradation studies were carried out by measurement of pH and %
      remaining weight. Viscoelastic characteristics of the samples indicated that all
      of the prepared IBS were injectable and they hardened at approximately 37 
      degrees C. Moreover, with increasing wt % of the bioceramic component, the
      degradation rate of the samples significantly reduced and the mechanical
      properties were improved. Therefore, the experimental results indicated that the
      P50 mix may be a promising candidates to fill bone defects and assist bone
      recovery for non-load bearing applications.

PMID- 29662020
TI  - Pheochromocytoma (PC12) Cell Response on Mechanobactericidal Titanium Surfaces.
AB  - Titanium is a biocompatible material that is frequently used for making
      implantable medical devices. Nanoengineering of the surface is the common method
      for increasing material biocompatibility, and while the nanostructured materials
      are well-known to represent attractive substrata for eukaryotic cells, very
      little information has been documented about the interaction between mammalian
      cells and bactericidal nanostructured surfaces. In this study, we investigated
      the effect of bactericidal titanium nanostructures on PC12 cell attachment and
      differentiation&mdash;a cell line which has become a widely used in vitro model
      to study neuronal differentiation. The effects of the nanostructures on the cells
      were then compared to effects observed when the cells were placed in contact with
      non-structured titanium. It was found that bactericidal nanostructured surfaces
      enhanced the attachment of neuron-like cells. In addition, the PC12 cells were
      able to differentiate on nanostructured surfaces, while the cells on non
      structured surfaces were not able to do so. These promising results demonstrate
      the potential application of bactericidal nanostructured surfaces in biomedical
      applications such as cochlear and neuronal implants.

PMID- 29662019
TI  - Liposomal Drug Delivery Systems and Anticancer Drugs.
AB  - Cancer is a life-threatening disease contributing to ~3.4 million deaths
      worldwide. There are various causes of cancer, such as smoking, being overweight
      or obese, intake of processed meat, radiation, family history, stress,
      environmental factors, and chance. The first-line treatment of cancer is the
      surgical removal of solid tumours, radiation therapy, and chemotherapy. The
      systemic administration of the free drug is considered to be the main clinical
      failure of chemotherapy in cancer treatment, as limited drug concentration
      reaches the tumour site. Most of the active pharmaceutical ingredients (APIs)
      used in chemotherapy are highly cytotoxic to both cancer and normal cells.
      Accordingly, targeting the tumour vasculatures is essential for tumour treatment.
      In this context, encapsulation of anti-cancer drugs within the liposomal system
      offers secure platforms for the targeted delivery of anti-cancer drugs for the
      treatment of cancer. This, in turn, can be helpful for reducing the cytotoxic
      side effects of anti-cancer drugs on normal cells. This short-review focuses on
      the use of liposomes in anti-cancer drug delivery.

PMID- 29662021
TI  - Roles of Polyploid/Multinucleated Giant Cancer Cells in Metastasis and Disease
      Relapse Following Anticancer Treatment.
AB  - Tumors and tumor-derived cell lines contain polyploid giant cells with
      significantly elevated genomic content, often with multiple nuclei. The frequency
      of giant cells can increase markedly following anticancer treatment. Although
      giant cells enter a dormant phase and therefore do not form macroscopic colonies
      (aggregates of >=50 cells) in the conventional in vitro colony formation assay,
      they remain viable and metabolically active. The purpose of this commentary is to
      underscore the potential importance of polyploid/multinucleated giant cells in
      metastasis and cancer recurrence following exposure to anticancer agents. We also
      discuss the possibility that most preclinical (cell-based and animal model) drug
      discovery approaches might not account for delayed responses that are associated
      with dormant giant cells.

PMID- 29662022
TI  - Parental Opinions and Attitudes about Children's Vaccination Safety in Silesian
      Voivodeship, Poland.
AB  - Despite mandatory vaccinations in Poland, the final decision on vaccination in
      children is taken by their parents or legal guardians. Understanding parents'
      attitudes and opinions regarding vaccinations is essential for planning and
      undertaking extensive and properly targeted educational actions aimed at
      preventing their hesitancy. In 2016, a cross-sectional study was conducted in the
      Silesian Voivodeship (Poland) in 11 randomly selected educational institutions.
      The authors' self-administered questionnaire contained 24 mixed-type questions.
      It was distributed among 3000 parents or legal guardians of children aged 6-13
      years; prior consent of the relevant bioethics committee had been obtained. The
      response rate was 41.3% (N = 1239). Data were analysed using descriptive and
      analytical statistics, and focused on parental opinions regarding the safety of
      vaccines. Results of simple and multivariable analyses showed that perceived risk
      of adverse vaccine reaction (AVR), contraindications and perception of the
      qualification procedure for vaccination as substandard were significant factors
      associated with the rating of children's vaccination as unsafe (p < 0.001).
      Respondents with a lower level of education, compared with those with higher,
      more often declared vaccinations to be safe (p = 0.03); however, results of
      multivariable analysis did not confirm that effect. AVR occurrence, finding of
      contraindication to vaccinations and perception of qualification procedure for
      vaccination were found to be the most important factors responsible for
      influencing general public opinions in the field of vaccination safety.

PMID- 29662023
TI  - Serum Is Not Necessary for Prior Pharmacological Activation of AMPK to Increase
      Insulin Sensitivity of Mouse Skeletal Muscle.
AB  - Exercise, contraction, and pharmacological activation of AMP-activated protein
      kinase (AMPK) by 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) have all
      been shown to increase muscle insulin sensitivity for glucose uptake.
      Intriguingly, improvements in insulin sensitivity following contraction of
      isolated rat and mouse skeletal muscle and prior AICAR stimulation of isolated
      rat skeletal muscle seem to depend on an unknown factor present in serum. One
      study recently questioned this requirement of a serum factor by showing serum
      independency with muscle from old rats. Whether a serum factor is necessary for
      prior AICAR stimulation to increase insulin sensitivity of mouse skeletal muscle
      is not known. Therefore, we investigated the necessity of serum for this effect
      of AICAR in mouse skeletal muscle. We found that the ability of prior AICAR
      stimulation to improve insulin sensitivity of mouse skeletal muscle did not
      depend on the presence of serum during AICAR stimulation. Although prior AICAR
      stimulation did not enhance proximal insulin signaling, insulin-stimulated
      phosphorylation of Tre-2/BUB2/CDC16- domain family member 4 (TBC1D4) Ser711 was
      greater in prior AICAR-stimulated muscle compared to all other groups. These
      results imply that the presence of a serum factor is not necessary for prior AMPK
      activation by AICAR to enhance insulin sensitivity of mouse skeletal muscle.

PMID- 29662024
TI  - PKIDB: A Curated, Annotated and Updated Database of Protein Kinase Inhibitors in
      Clinical Trials.
AB  - The number of protein kinase inhibitors (PKIs) approved worldwide continues to
      grow steadily, with 39 drugs approved in the period between 2001 and January
      2018. PKIs on the market have been the subject of many reviews, and structure
      property relationships specific to this class of drugs have been inferred.
      However, the large number of PKIs under development is often overlooked. In this
      paper, we present PKIDB (Protein Kinase Inhibitor Database), a monthly-updated
      database gathering approved PKIs as well as PKIs currently in clinical trials.
      The database compiles currently 180 inhibitors ranging from phase 0 to 4 clinical
      trials along with annotations extracted from seven public resources. The
      distribution and property ranges of standard physicochemical properties are
      presented. They can be used as filters to better prioritize compound selection
      for future screening campaigns. Interestingly, more than one-third of the kinase
      inhibitors violate at least one Lipinski's rule. A Principal Component Analysis
      (PCA) reveals that Type-II inhibitors are mapped to a distinct chemical space as
      compared to orally administrated drugs as well as to other types of kinase
      inhibitors. Using a Principal Moment of Inertia (PMI) analysis, we show that PKIs
      under development tend to explore new shape territories as compared to approved
      PKIs. In order to facilitate the analysis of the protein space, the kinome tree
      has been annotated with all protein kinases being targeted by PKIs. Finally, we
      analyzed the pipeline of the pharmaceutical companies having PKIs on the market
      or still under development. We hope that this work will assist researchers in the
      kinase field in identifying and designing the next generation of kinase
      inhibitors for still untargeted kinases. The PKIDB database is freely accessible
      from a website at http://www.icoa.fr/pkidb and can be easily browsed through a
      user-friendly spreadsheet-like interface.

PMID- 29662025
TI  - Biochemical Characterization and Degradation Pattern of a Unique pH-Stable PolyM
      Specific Alginate Lyase from Newly Isolated Serratia marcescens NJ-07.
AB  - Enzymatic preparation of alginate oligosaccharides with versatile bioactivities
      by alginate lyases has attracted increasing attention due to its featured
      characteristics, such as wild condition and specific products. In this study,
      AlgNJ-07, a novel polyM-specific alginate lyase with high specific activity and
      pH stability, has been purified from the newly isolated marine bacterium Serratia
      marcescens NJ-07. It has a molecular weight of approximately 25 kDa and exhibits
      the maximal activity of 2742.5 U/mg towards sodium alginate under 40  degrees C
      at pH 9.0. Additionally, AlgNJ-07 could retain more than 95% of its activity at
      pH range of 8.0-10.0, indicating it possesses excellent pH-stability. Moreover,
      it shows high activity and affinity towards polyM block and no activity to polyG
      block, which suggests that it is a strict polyM-specific alginate lyase. The
      degradation pattern of AlgNJ-07 has also been explored. The activity of AlgNJ-07
      could be activated by NaCl with a low concentration (100-300 mM). It can be
      observed that AlgNJ-07 can recognize the trisaccharide as the minimal substrate
      and hydrolyze the trisaccharide into monosaccharide and disaccharide. The TLC and
      ESI-MS analysis indicate that it can hydrolyze substrates in a unique endolytic
      manner, producing not only oligosaccharides with Dp of 2-5 but also a large
      fraction of monosaccharide. Therefore, it may be a potent tool to produce
      alginate oligosaccharides with lower Dps (degree of polymerization).

PMID- 29662027
TI  - Pharmacokinetic-Pharmacodynamic Model for the Testosterone-Suppressive Effect of
      Leuprolide in Normal and Prostate Cancer Rats.
AB  - This study developed the pharmacokinetic (PK)-pharmacodynamic (PD) model of the
      testosterone-suppressive effect of leuprolide for evaluation of the sustained
      release (SR) depot and leuprolide solution in rats with or without prostate
      cancer. Six groups of rats were divided by the routes of administration
      (intravenous and subcutaneous injection) and kinds of formulation (vehicle,
      leuprolide solution, and SR depot). The PK profile after subcutaneous injection
      of leuprolide solution could be well-described by the one-compartment model. The
      absorption rate constant, the total body clearance, and the volume of
      distribution were estimated at 16.67 h-1, 514.46 mL/h, and 487.40 mL. Using PK
      parameters in the solution-administered group, the PK model for the SR depot was
      developed. The PK-PD model was constructed by describing the testosterone
      suppressive effect of leuprolide using the feedback turnover model. The response
      of testosterone after administration of each formulation was well described using
      this PK-PD model for the estimation of PD parameters (EC50, Emax, h) and systemic
      parameters (kin, kout, kf on, kf off). The developed PK-PD model containing an
      inhibitory feedback system could successfully describe the testosterone
      suppressive effect of leuprolide in the type of formulation. The PK-PD model
      developed would be useful for evaluating the formulation of similar drugs whose
      effect is regulated through the feedback mechanism.

PMID- 29662026
TI  - The Hard Way towards an Antibody-Based HIV-1 Env Vaccine: Lessons from Other
      Viruses.
AB  - Although effective antibody-based vaccines have been developed against multiple
      viruses, such approaches have so far failed for the human immunodeficiency virus
      type 1 (HIV-1). Despite the success of anti-retroviral therapy (ART) that has
      turned HIV-1 infection into a chronic disease and has reduced the number of new
      infections worldwide, a vaccine against HIV-1 is still urgently needed. We
      discuss here the major reasons for the failure of "classical" vaccine approaches,
      which are mostly due to the biological properties of the virus itself. HIV-1 has
      developed multiple mechanisms of immune escape, which also account for vaccine
      failure. So far, no vaccine candidate has been able to induce broadly
      neutralizing antibodies (bnAbs) against primary patient viruses from different
      clades. However, such antibodies were identified in a subset of patients during
      chronic infection and were shown to protect from infection in animal models and
      to reduce viremia in first clinical trials. Their detailed characterization has
      guided structure-based reverse vaccinology approaches to design better HIV-1
      envelope (Env) immunogens. Furthermore, conserved Env epitopes have been
      identified, which are promising candidates in view of clinical applications.
      Together with new vector-based technologies, considerable progress has been
      achieved in recent years towards the development of an effective antibody-based
      HIV-1 vaccine.

PMID- 29662028
TI  - Nitrate Reductases Are Relocalized to the Nucleus by AtSIZ1 and Their Levels Are
      Negatively Regulated by COP1 and Ammonium.
AB  - Nitrate reductases (NRs) catalyze the first step in the reduction of nitrate to
      ammonium. NR activity is regulated by sumoylation through the E3 ligase activity
      of AtSIZ1. However, it is not clear how NRs interact with AtSIZ1 in the cell, or
      how nitrogen sources affect NR levels and their cellular localization. Here, we
      show that the subcellular localization of NRs is modulated by the E3 SUMO (Small
      ubiquitin-related modifier) ligase AtSIZ1 and that NR protein levels are
      regulated by nitrogen sources. Transient expression analysis of GFP fusion
      proteins in onion epidermal cells showed that the NRs NIA1 and NIA2 localize to
      the cytoplasmic membrane, and that AtSIZ1 localizes to the nucleoplasm, including
      nuclear bodies, when expressed separately, whereas NRs and AtSIZ1 localize to the
      nucleus when co-expressed. Nitrate did not affect the subcellular localization of
      the NRs, but it caused AtSIZ1 to move from the nucleus to the cytoplasm. NRs were
      not detected in ammonium-treated cells, whereas the localization of AtSIZ1 was
      not altered by ammonium treatment. NR protein levels increased in response to
      nitrate but decreased in response to ammonium. In addition, NR protein levels
      increased in response to a 26S proteasome inhibitor and in cop1-4 and DN-COP1
      overexpressing transgenic plants. NR protein degradation occurred later in cop1-4
      than in the wild-type, although the NR proteins did not interact with COP1.
      Therefore, AtSIZ1 controls nuclear localization of NR proteins, and ammonium
      negatively regulates their levels. The function and stability of NR proteins
      might be post-translationally modulated by ubiquitination.

PMID- 29662029
TI  - Stryphnodendron Species Known as "Barbatimao": A Comprehensive Report.
AB  - Stryphnodendron spp., popularly known as "barbatimao", is the native Brazilian
      tree most often employed to treat wounds and infections. The aim of the present
      study was to highlight the importance of S. adstringens, as well as other
      Stryphnodendron species recognized as "barbatimao", to human health, depicting
      the relevance of ethnopharmacological knowledge to scientific evidence for uses,
      related chemical compounds, development of pharmaceutical formulations, and the
      establishment of toxicity parameters. For this purpose, the literature databases
      PubMed, Scielo, Lilacs, CAPES Thesis and Google Scholar were searched until 2017.
      It was observed that stem bark was the primary part of the plant used, mainly as
      a decoction, for wound healing and treatment of infectious and inflammatory
      disorders. Confirmed biological activities, including wound healing, anti
      inflammatory, antioxidant, and antimicrobial activities, were related to the
      presence of compounds from tannin class, mostly proanthocyanidins. Toxicity
      parameters for stem bark were inconclusive, but toxicity was observed to a
      significant extent when seeds were ingested by cattle or other animals. Due to
      these important and confirmed biological activities, government policy encourages
      the phytotherapic use of S. adstringens, and some formulations with stem bark
      extracts were developed and patented. Furthermore, antiprotozoal, hypoglycemic
      and antiviral activities were identified as promising.

PMID- 29662030
TI  - From Protein Features to Sensing Surfaces.
AB  - Proteins play a major role in biosensors in which they provide catalytic activity
      and specificity in molecular recognition. However, the immobilization process is
      far from straightforward as it often affects the protein functionality. Extensive
      interaction of the protein with the surface or significant surface crowding can
      lead to changes in the mobility and conformation of the protein structure. This
      review will provide insights as to how an analysis of the physico-chemical
      features of the protein surface before the immobilization process can help to
      identify the optimal immobilization approach. Such an analysis can help to
      preserve the functionality of the protein when on a biosensor surface.

PMID- 29662031
TI  - The Associations between Sleep Duration and Sleep Quality with Body-Mass Index in
      a Large Sample of Young Adults.
AB  - BACKGROUND: The main aims of this study were to explore the associations between
      time spent in bed (as a proxy of sleep duration) and sleep quality with
      overweight/obesity status in a large sample of young adults. METHODS: In this
      cross-sectional study, participants were 2100 university students (49.6% of
      women). We used Pittsburgh Sleep Quality Index (PSQI) questionnaire to assess
      time spent in bed and sleep quality. Body-mass index (BMI) was self-reported and
      dichotomized as normal (<25 kg/m2) vs. overweight/obesity (>=25 kg/m2) status.
      RESULTS: In model 1, both short (<6 h/day, OR = 2.72; 95% CI 1.27 to 5.84) and
      long (>10 h/day, OR = 3.38; 95% CI 2.12 to 5.40) time spent in bed were
      associated with a greater likelihood of being overweight/obese. In model 2, poor
      sleep quality (>5 points, OR = 1.45; 95% CI 1.14 to 1.83) was associated with a
      greater likelihood of being overweight/obese. After entering time spent in bed
      and sleep quality simultaneously into the model 3, both short (OR = 2.64; 95% CI
      1.23 to 5.66) and long (OR = 3.27; 95% CI 2.04 to 5.23) time spent in bed and
      poor sleep quality (OR = 1.40; 95% CI 1.10 to 1.78) were associated with
      overweight/obesity status. CONCLUSIONS: Our results show that both short and long
      time spent in bed and poor sleep quality are associated with overweight/obesity
      status in young adults. Special interventions and policies that use both sleep
      duration and sleep quality as protective factors against overweight/obesity are
      warranted.

PMID- 29662032
TI  - Cardiovascular-Related Outcomes in U.S. Adults Exposed to Lead.
AB  - Cardiovascular-related clinical markers were evaluated in this cross-sectional
      study of United States adults (aged >= 20) exposed to lead via the National
      Health and Nutrition Examination Survey 2007-2008 and the 2009-2010 datasets. In
      four quartiles of exposure-0-2 MUg/dL, 2-5 MUg/dL, 5-10 MUg/dL, and 10 MUg/dL and
      over, clinical and anthropometric markers were evaluated-to examine how the
      markers manifested in the quartiles. Associations were determined via linear
      regression. Finally, clinical makers, and how they manifested between exposed and
      less-exposed occupations, were explored in addition to how duration of exposure
      altered these clinical markers. In regression analysis, Diastolic Blood Pressure
      (DBP) and high-density lipoprotein (HDL) cholesterol, were significantly
      associated with blood lead level (BLL). In the occupational analysis, Systolic
      Blood Pressure (SBP), DBP, C-reactive protein (CRP), triglycerides, low-density
      lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, showed
      differences between populations in the exposed and less-exposed occupations.
      Regarding Agriculture, Forestry & Fishing, the duration of exposure altered SBP,
      CRP, and LDL cholesterol. With mining, the duration of exposure altered SBP, DBP,
      triglycerides, and HDL cholesterol, whereas in construction, the duration in
      occupation altered SBP, triglycerides, and CRP. In conclusion, lead exposure has
      a profound effect on the cardiovascular system, with potentially adverse outcomes
      existing at all exposure levels.

PMID- 29662033
TI  - Evaluating Molecular Properties Involved in Transport of Small Molecules in
      Stratum Corneum: A Quantitative Structure-Activity Relationship for Skin
      Permeability.
AB  - The skin permeability (Kp) defines the rate of a chemical penetrating across the
      stratum corneum. This value is widely used to quantitatively describe the
      transport of molecules in the outermost layer of epidermal skin and indicate the
      significance of skin absorption. This study defined a Kp quantitative structure
      activity relationship (QSAR) based on 106 chemical substances of Kp measured
      using human skin and interpreted the molecular interactions underlying transport
      behavior of small molecules in the stratum corneum. The Kp QSAR developed in this
      study identified four molecular descriptors that described the molecular
      cyclicity in the molecule reflecting local geometrical environments, topological
      distances between pairs of oxygen and chlorine atoms, lipophilicity, and
      similarity to antineoplastics in molecular properties. This Kp QSAR considered
      the octanol-water partition coefficient to be a direct influence on transdermal
      movement of molecules. Moreover, the Kp QSAR identified a sub-domain of molecular
      properties initially defined to describe the antineoplastic resemblance of a
      compound as a significant factor in affecting transdermal permeation of solutes.
      This finding suggests that the influence of molecular size on the chemical's skin
      permeating capability should be interpreted with other relevant physicochemical
      properties rather than being represented by molecular weight alone.

PMID- 29662034
TI  - Inline Determination of Residence Time Distribution in Hot-Melt-Extrusion.
AB  - In the framework of Quality-by-Design (QbD), the inline determination of process
      parameters or quality attributes of a product using sufficient process analytical
      technology (PAT) is a center piece for the establishment of continuous processes
      as a standard pharmaceutical technology. In this context, Twin-Screw-Extrusion
      (TSE) processes, such as Hot-Melt-Extrusion (HME), are one key aspect of current
      research. The main benefit of this process technology is the combination of
      different unit operations. Several of these sub-processes are linked to the
      Residence Time Distribution (RTD) of the material within the apparatus. In this
      study a UV/Vis spectrophotometer from ColVisTec was tested regarding the
      suitability for the inline determination of the RTD of an HME process. Two
      different measuring positions within a co-rotating Twin-Screw-Extruder were
      compared to an offline HPLC-UV as reference method. The obtained results were
      overall in good agreement and therefore the inline UV/Vis spectrophotometer is
      suitable for the determination of the RTD in TSE. An influence of the measuring
      position on repeatability was found and has to be taken into consideration for
      the implementation of PATs. An effect of the required amount of marker on process
      rheology is not likely due to the low Limit-of-Quantification (LoQ).

PMID- 29662035
TI  - Structure and Magnetism of Mn5Ge3 Nanoparticles.
AB  - In this work, we investigated the magnetic and structural properties of isolated
      Mn5Ge3 nanoparticles prepared by the cluster-beam deposition technique. Particles
      with sizes between 7.2 and 12.6 nm were produced by varying the argon pressure
      and power in the cluster gun. X-ray diffraction (XRD)and selected area
      diffraction (SAD) measurements show that the nanoparticles crystallize in the
      hexagonal Mn5Si3-type crystal structure, which is also the structure of bulk
      Mn5Ge3. The temperature dependence of the magnetization shows that the as-made
      particles are ferromagnetic at room temperature and have slightly different Curie
      temperatures. Hysteresis-loop measurements show that the saturation magnetization
      of the nanoparticles increases significantly with particle size, varying from 31
      kA/m to 172 kA/m when the particle size increases from 7.2 to 12.6 nm. The
      magnetocrystalline anisotropy constant K at 50 K, determined by fitting the high
      field magnetization data to the law of approach to saturation, also increases
      with particle size, from 0.4 * 105 J/m3 to 2.9 * 105 J/m3 for the respective
      sizes. This trend is mirrored by the coercivity at 50 K, which increases from
      0.04 T to 0.13 T. A possible explanation for the magnetization trend is a radial
      Ge concentration gradient.

PMID- 29662036
TI  - Electrochemical Aptamer-Based Sensors for Rapid Point-of-Use Monitoring of the
      Mycotoxin Ochratoxin A Directly in a Food Stream.
AB  - The ability to measure the concentration of specific small molecules continuously
      and in real-time in complex sample streams would impact many areas of
      agriculture, food safety, and food production. Monitoring for mycotoxin taint in
      real time during food processing, for example, could improve public health.
      Towards this end, we describe here an inexpensive electrochemical DNA-based
      sensor that supports real-time monitor of the mycotoxin ochratoxin A in a flowing
      stream of foodstuffs.

PMID- 29662037
TI  - Towards the Development of Global Nano-Quantitative Structure-Property
      Relationship Models: Zeta Potentials of Metal Oxide Nanoparticles.
AB  - Zeta potential indirectly reflects a charge of the surface of nanoparticles in
      solutions and could be used to represent the stability of the colloidal solution.
      As processes of synthesis, testing and evaluation of new nanomaterials are
      expensive and time-consuming, so it would be helpful to estimate an approximate
      range of properties for untested nanomaterials using computational modeling. We
      collected the largest dataset of zeta potential measurements of bare metal oxide
      nanoparticles in water (87 data points). The dataset was used to develop
      quantitative structure-property relationship (QSPR) models. Essential features of
      nanoparticles were represented using a modified simplified molecular input line
      entry system (SMILES). SMILES strings reflected the size-dependent behavior of
      zeta potentials, as the considered quasi-SMILES modification included information
      about both chemical composition and the size of the nanoparticles. Three
      mathematical models were generated using the Monte Carlo method, and their
      statistical quality was evaluated (R2 for the training set varied from 0.71 to
      0.87; for the validation set, from 0.67 to 0.82; root mean square errors for both
      training and validation sets ranged from 11.3 to 17.2 mV). The developed models
      were analyzed and linked to aggregation effects in aqueous solutions.

PMID- 29662038
TI  - Alignment of Boron Nitride Nanofibers in Epoxy Composite Films for Thermal
      Conductivity and Dielectric Breakdown Strength Improvement.
AB  - Development of polymer-based composites with simultaneously high thermal
      conductivity and breakdown strength has attracted considerable attention owing to
      their important applications in both electronic and electric industries. In this
      work, boron nitride (BN) nanofibers (BNNF) are successfully prepared as fillers,
      which are used for epoxy composites. In addition, the BNNF in epoxy composites
      are aligned by using a film casting method. The composites show enhanced thermal
      conductivity and dielectric breakdown strength. For instance, after doping with
      BNNF of 2 wt%, the thermal conductivity of composites increased by 36.4% in
      comparison with that of the epoxy matrix. Meanwhile, the breakdown strength of
      the composite with 1 wt% BNNF is 122.9 kV/mm, which increased by 6.8% more than
      that of neat epoxy (115.1 kV/mm). Moreover, the composites have maintained a low
      dielectric constant and alternating current conductivity among the range of full
      frequency, and show a higher thermal decomposition temperature and glass
      transition temperature. The composites with aligning BNNF have wide application
      prospects in electronic packaging material and printed circuit boards.

PMID- 29662039
TI  - Poly(vinyl Chloride) Photostabilization in the Presence of Schiff Bases
      Containing a Thiadiazole Moiety.
AB  - Five Schiff bases containing a thiadiazole moiety have been used as poly(vinyl
      chloride) photostabilizers at low concentrations. The efficiency of Schiff bases
      as photostabilizers was investigated using various techniques, for example, the
      changes in poly(vinyl chloride) infrared spectra, molecular weight, chain
      scission quantum yield, and surface morphology were monitored upon irradiation
      with an ultraviolet light. Evidently, all the additives used inhibited poly(vinyl
      chloride) photodegradation at a significant level. The most efficient Schiff base
      exhibited a high level of aromaticity and contained a hydroxyl group. It seems
      possible that such photostabilization could be due to the direct absorption of
      ultraviolet radiation by the additives. In addition, Schiff bases could act as
      radical scavengers and proton transfer facilitators to stabilize the polymeric
      materials.

PMID- 29662040
TI  - Liquid Membranes as a Tool for Chemical Speciation of Metals in Natural Waters:
      Organic and Inorganic Complexes of Nickel.
AB  - The different species of nickel present in natural waters exhibit different
      transport behaviour through bulk liquid membranes (BLMs). This fact has been used
      to design and optimise a separation/pre-concentration system applicable to
      separate labile and non-labile nickel fractions. A hydrazone derivative-1,2
      cyclohexanedione bis-benzoyl-hydrazone (1,2-CHBBH) dissolved in toluene/dimethyl
      formamide (2% DMF)-was used as a chemical carrier of nickel species, from an
      aqueous source solution (sample) to a receiving acidic solution. Both chemical
      and hydrodynamic conditions controlling the transport system were studied and
      optimised. Under optimum conditions, variations in the transport of nickel ions
      as a function of organic (humic acids) and inorganic (chloride ions) ligands were
      studied. Relationships between the permeability coefficient (P) or recovery
      efficiency (%R) and the concentrations of ligands and nickel species were
      analysed using Winhumic V software. A negative correlation between P and the
      concentration of organic nickel complexes was found, suggesting that only labile
      nickel species are transported through the liquid membrane, with non-labile
      complexes remaining in the water sample; allowing for their separation and
      subsequent quantification in natural waters.

PMID- 29662042
TI  - One-Pot, Highly Stereoselective Synthesis of Dithioacetal-alpha,alpha
      Diglycosides.
AB  - A one-step access to dithioacetal-alpha,alpha-diglycosides is reported. The
      synthetic strategy is based on the thioacetalization of aldehydes or ketones via
      highly stereoselective ring-opening of 1,6 anhydrosugars with
      bis(trimethylsilyl)sulfide.

PMID- 29662041
TI  - Formulation, Development, and In Vitro Evaluation of a CD22 Targeted Liposomal
      System Containing a Non-Cardiotoxic Anthracycline for B Cell Malignancies.
AB  - Doxorubicin cardiotoxicity has led to the development of superior
      chemotherapeutic agents such as AD 198. However, depletion of healthy neutrophils
      and thrombocytes from AD 198 therapy must be limited. This can be done by the
      development of a targeted drug delivery system that delivers AD 198 to the
      malignant cells. The current research highlights the development and in vitro
      analysis of targeted liposomes containing AD 198. The best lipids were identified
      and optimized for physicochemical effects on the liposomal system. Physiochemical
      characteristics such as size, &zeta;-potential, and dissolution were also
      studied. Active targeting to CD22 positive cells was achieved by conjugating anti
      CD22 Fab&rsquo; to the liposomal surface. Size and &zeta;-potential of the
      liposomes was between 115 and 145 nm, and &minus;8 to&minus;15 mV. 30% drug was
      released over 72 h. Higher cytotoxicity was observed in CD22+ve Daudi cells
      compared to CD22&minus;ve Jurkat cells. The route of uptake was a clathrin- and
      caveolin-independent pathway. Intracellular localization of the liposomes was in
      the endolysosomes. Upon drug release, apoptotic pathways were activated partly by
      the regulation of apoptotic and oncoproteins such as caspase-3 and c-myc. It was
      observed that the CD22 targeted drug delivery system was more potent and specific
      compared to other untargeted formulations.

PMID- 29662043
TI  - Big Data Clustering via Community Detection and Hyperbolic Network Embedding in
      IoT Applications.
AB  - In this paper, we present a novel data clustering framework for big sensory data
      produced by IoT applications. Based on a network representation of the relations
      among multi-dimensional data, data clustering is mapped to node clustering over
      the produced data graphs. To address the potential very large scale of such
      datasets/graphs that test the limits of state-of-the-art approaches, we map the
      problem of data clustering to a community detection one over the corresponding
      data graphs. Specifically, we propose a novel computational approach for
      enhancing the traditional Girvan-Newman (GN) community detection algorithm via
      hyperbolic network embedding. The data dependency graph is embedded in the
      hyperbolic space via Rigel embedding, allowing more efficient computation of edge
      betweenness centrality needed in the GN algorithm. This allows for more efficient
      clustering of the nodes of the data graph in terms of modularity, without
      sacrificing considerable accuracy. In order to study the operation of our
      approach with respect to enhancing GN community detection, we employ various
      representative types of artificial complex networks, such as scale-free, small
      world and random geometric topologies, and frequently-employed benchmark datasets
      for demonstrating its efficacy in terms of data clustering via community
      detection. Furthermore, we provide a proof-of-concept evaluation by applying the
      proposed framework over multi-dimensional datasets obtained from an operational
      smart-city/building IoT infrastructure provided by the Federated Interoperable
      Semantic IoT/cloud Testbeds and Applications (FIESTA-IoT) testbed federation. It
      is shown that the proposed framework can be indeed used for community
      detection/data clustering and exploited in various other IoT applications, such
      as performing more energy-efficient smart-city/building sensing.

PMID- 29662044
TI  - Vitamin D Deficiency Prevalence and Predictors in Early Pregnancy among Arab
      Women.
AB  - Data regarding the prevalence and predictors of vitamin D deficiency during early
      pregnancy are limited. This study aims to fill this gap. A total of 578 Saudi
      women in their 1st trimester of pregnancy were recruited between January 2014 and
      December 2015 from three tertiary care antenatal clinics in Riyadh, Saudi Arabia.
      Information collected includes socio-economic, anthropometric, and biochemical
      data, including serum vitamin D (25(OH)D) levels, intake of calcium and vitamin
      D, physical activity, and sun exposure indices. Pregnant women with 25(OH)D
      levels <50 nmol/L were considered vitamin D deficient. The majority of
      participants (n = 468 (81%)) were vitamin D deficient. High levels of indoor
      activity, whole body clothing, multiparity, total cholesterol/HDL ratio(>3.5),
      low HDL-cholesterol, and living in West Riyadh were significant independent
      predictors for vitamin D deficiency, with odds ratios (ORs) (95% confidence
      interval) of 25.4 (5.5&ndash;117.3), 17.8 (2.3&ndash;138.5), 4.0 (1.7&ndash;9.5),
      3.3 (1.4&ndash;7.9), 2.8 (1.2&ndash;6.4), and 2.0 (1.1&ndash;3.5), respectively.
      Factors like increased physical activity, sun exposure at noon, sunrise or
      sunset, high educational status, and residence in North Riyadh were protective
      against vitamin D deficiency with ORs 0.2 (0.1&ndash;0.5); 0.2 (0.1&ndash;0.6);
      0.3 (0.1&ndash;0.9); and 0.4 (0.2&ndash;0.8), respectively. All ORs were adjusted
      for age, BMI, sun exposure, parity, summer season, vitamin D intake, multivitamin
      intake, physical activity, education, employment, living in the north, and
      coverage with clothing. In conclusion, the prevalence of vitamin D deficiency
      among Saudi women during early pregnancy was high (81%). Timely detection and
      appropriate supplementation with adequate amounts of vitamin D should reduce the
      risks of vitamin D deficiency and its complications during pregnancy.

PMID- 29662046
TI  - Near-Drowning: To Be or Not to Be ... Is It the Question?

PMID- 29662045
TI  - Macronutrient and Major Food Group Intake in a Cohort of Southern Italian Adults.
AB  - BACKGROUND: Dietary intake of macronutrient and foods is considered crucial to
      decrease the risk of diet-related non-communicable diseases. METHODS: The aim of
      this study was to describe the intake of major food groups and macronutrients in
      a random sample of 1838 southern Italian adults. RESULTS: No significant
      differences of macronutrient consumption between sexes were found. By contrast,
      younger individuals had significantly higher intake of animal protein than older
      ones. Men reported consuming significantly more total processed meats and less
      eggs than women; egg consumption significantly increased by age groups.
      Significantly lower intake of fruit in the younger age group compared to older
      ones was found. Various patterns of correlation between food groups were
      described. More than half of individuals reached the suggested recommendations
      for carbohydrate and fiber intake, and about two-thirds met the recommendations
      for total protein and cholesterol intake, while only a minority met for total fat
      intake. Total and plant protein, monounsaturated and omega-6 fatty acids, were
      significantly inversely related with BMI (body mass index), while trans fatty
      acids and cholesterol were directly correlated. A direct association with
      unprocessed meats and an inverse association with processed meats was also found.
      CONCLUSIONS: The overall findings suggest that relatively healthy dietary habits
      are common in southern Italy.

PMID- 29662047
TI  - Mechanisms and FEM Simulation of Chip Formation in Orthogonal Cutting In-Situ
      TiB2/7050Al MMC.
AB  - The in-situ TiB2/7050Al composite is a new kind of Al-based metal matrix
      composite (MMC) with super properties, such as low density, improved strength,
      and wear resistance. This paper, for a deep insight into its cutting performance,
      involves a study of the chip formation process and finite element simulation
      during orthogonal cutting in-situ TiB2/7050Al MMC. With chips, material
      properties, cutting forces, and tool geometry parameters, the Johnson-Cook (J-C)
      constitutive equation of in-situ TiB2/7050Al composite was established. Then, the
      cutting simulation model was established by applying the Abaqus-Explicit method,
      and the serrated chip, shear plane, strain rate, and temperature were analyzed.
      The experimental and simulation results showed that the obtained material's
      constitutive equation was of high reliability, and the saw-tooth chips occurred
      commonly under either low or high cutting speed and small or large feed rate.
      From result analysis, it was found that the mechanisms of chip formation included
      plastic deformation, adiabatic shear, shearing slip, and crack extension. In
      addition, it was found that the existence of small, hard particles reduced the
      ductility of the MMC and resulted in segmental chips.

PMID- 29662048
TI  - "What Is a Step?" Differences in How a Step Is Detected among Three Popular
      Activity Monitors That Have Impacted Physical Activity Research.
AB  - (1) Background: This study compared manually-counted treadmill walking steps from
      the hip-worn DigiwalkerSW200 and OmronHJ720ITC, and hip and wrist-worn ActiGraph
      GT3X+ and GT9X; determined brand-specific acceleration amplitude (g) and/or
      frequency (Hz) step-detection thresholds; and quantified key features of the
      acceleration signal during walking. (2) Methods: Twenty participants (Age: 26.7
      +/- 4.9 years) performed treadmill walking between 0.89-to-1.79 m/s (2-4 mph)
      while wearing a hip-worn DigiwalkerSW200, OmronHJ720ITC, GT3X+ and GT9X, and a
      wrist-worn GT3X+ and GT9X. A DigiwalkerSW200 and OmronHJ720ITC underwent shaker
      testing to determine device-specific frequency and amplitude step-detection
      thresholds. Simulated signal testing was used to determine thresholds for the
      ActiGraph step algorithm. Steps during human testing were compared using bias and
      confidence intervals. (3) Results: The OmronHJ720ITC was most accurate during
      treadmill walking. Hip and wrist-worn ActiGraph outputs were significantly
      different from the criterion. The DigiwalkerSW200 records steps for movements
      with a total acceleration of >=1.21 g. The OmronHJ720ITC detects a step when
      movement has an acceleration >=0.10 g with a dominant frequency of >=1 Hz. The
      step-threshold for the ActiLife algorithm is variable based on signal frequency.
      Acceleration signals at the hip and wrist have distinctive patterns during
      treadmill walking. (4) Conclusions: Three common research-grade physical activity
      monitors employ different step-detection strategies, which causes variability in
      step output.

PMID- 29662049
TI  - Acute Lymphoblastic Leukemia Presenting with Liver Infiltration and Severe Lactic
      Acidosis.
AB  - BACKGROUND Type-B lactic acidosis is a rare complication of solid tumors and
      hematological malignancies. It occurs secondary to Warburg effect, when glucose
      metabolism in cancer cells switches from the oxidative pathway to the glycolytic
      pathway. Malignant lactic acidosis is a life-threatening condition if not
      promptly diagnosed and treated urgently. CASE REPORT We report the case of a 58
      year-old male patient who presented with severe chest pain, dyspnea, systemic
      symptoms, leukopenia, normocytic anemia, and severe lactic acidosis. He was
      admitted with a possible diagnosis of acute pericarditis and lactic acidosis.
      Sodium bicarbonate replacement did not improve the lactic acidosis. Liver biopsy
      was performed because of persistently elevated alkaline phosphatase and gamma
      glutamyl transferase; the biopsy showed atypical lymphoblasts and bone marrow
      biopsy confirmed the diagnosis of precursor B acute lymphoblastic leukemia.
      Lactic acidosis normalized after initiation of chemotherapy. CONCLUSIONS Cancer,
      particularly hematological malignancy, should be considered as an etiology and
      differential diagnosis of type-B lactic acidosis. Prompt recognition and urgent
      initiation of specific therapy to control the underlying malignancy are critical
      to manage this serious metabolic complication.

PMID- 29662050
TI  - Does Vitamin D Affect Chronic Renal Allograft Function in Pediatric Transplant
      Patients?
AB  - BACKGROUND Correction of hypovitaminosis D is simple, but it is unclear whether
      it is associated with an accelerated decline of renal allograft function in
      pediatric renal transplantation patients. This retrospective single center cohort
      study aimed at analyzing the effect of vitamin D and covariates on the slope of
      1/creatinine after the first year. MATERIAL AND METHODS After ethics committee
      approval, 37 (14 male) pediatric renal transplant recipients on mycophenolate
      mofetil, who were followed between 2006 and 2014, were included in this study. We
      analyzed the slope of 1/creatinine, length of follow-up, average vitamin D
      levels, calcium, phosphate, alkaline phosphatase levels, intact parathyroid
      hormone (PTH) levels, and therapeutic drug monitoring parameters. RESULTS Median
      slope of 1/creatinine was -2.587e-006 L/umol. We divided the 37 patients into two
      groups based on slope: 18 patients with a poorer slope and 19 patients with a
      good slope, with the median slope of 1/creatinine being significantly different
      between the two groups. Creatinine and cystatin C at one-year post
      transplantation did not differ between the two groups. Average vitamin D levels
      were 71.4+/-31.01 pmol/L and identical in each group (averages 71.67 and 69.23
      pmol/L, respectively). Only the mycophenolic acid coefficient of variation (MPA
      CV), which may promote formation of donor-specific antibodies, and PTH levels
      were significantly associated with 1/creatinine slope. CONCLUSIONS Our data
      suggest that the impact of mild and moderate decreased levels of vitamin D can
      have a mild impact on the progression of allograft dysfunction in transplant
      recipients. However, given the medication burden and adherence challenges in
      adolescents, correction of mildly decreased vitamin D levels may not be
      necessary.

PMID- 29662051
TI  - [Knowledge and attitudes toward organ donation among health professionals in a
      third level hospital].
AB  - OBJECTIVE: The Spanish model is the model adopted by many countries to increase
      their donation rate, being the implication of the healthcare professionals one of
      the keys to this success. The attitude of these before the donation is crucial
      for the hour of influence on the population. Organ transplantation has been
      established as an effective treatment that has been improving over the years. The
      objective was to determine the knowledge and attitudes of health professionals
      before the donation of organs. METHODS: Cross-sectional descriptive study. An ad
      hoc questionnaire was conducted and distributed among the health professionals
      (medical staff, nurses and nursing assistants) of a tertiary hospital during
      February 2015. A total of 615 potential participants were estimated in the
      different areas of the hospital. A total of 342 completed questionnaires were
      collected (55%). The statistical analysis with SPSS(r) Statistics for Windows.
      Version 20.0. A level of significance P lower than 0.05 was used in all the
      analyses. RESULTS: The average age of the respondents was 43.34 (SD = 10.37)
      years, being 86.6% women and 60% nurses. 35.5% showed good knowledge about the
      donation process, being higher in men (51.1% Vs 33.1%, p lower than 0.05),
      medical personnel (55% vs 34.3% vs 31.9%). %; p lower than 0.05) and lower in
      those services with a direct relationship with the donation process (36.8% vs
      31.9%, p lower than 0.05). 71% of the professionals expressed their willingness
      to donate their organs, with special sensitivity towards donation those services
      in direct relation with the donation program (82.2% vs 65.9%, OR: 1.24, p lower
      than 0.001 ). 50% of the professionals would donate the organs of a family
      member; the medical group had the highest percentage (70% vs 50.7% vs 40.4%, OR:
      3.8, p lower than 0.05). 74.5% knew some Spanish legal document about donation
      and transplants. CONCLUSIONS: Health professionals as a whole have a low level of
      knowledge; but a good attitude towards donation.

PMID- 29662052
TI  - Ultra-thin high-efficiency mid-infrared transmissive Huygens meta-optics.
AB  - The mid-infrared (mid-IR) is a strategically important band for numerous
      applications ranging from night vision to biochemical sensing. Here we
      theoretically analyzed and experimentally realized a Huygens metasurface platform
      capable of fulfilling a diverse cross-section of optical functions in the mid-IR.
      The meta-optical elements were constructed using high-index chalcogenide films
      deposited on fluoride substrates: the choices of wide-band transparent materials
      allow the design to be scaled across a broad infrared spectrum. Capitalizing on a
      two-component Huygens' meta-atom design, the meta-optical devices feature an
      ultra-thin profile (lambda0/8 in thickness) and measured optical efficiencies up
      to 75% in transmissive mode for linearly polarized light, representing major
      improvements over state-of-the-art. We have also demonstrated mid-IR transmissive
      meta-lenses with diffraction-limited focusing and imaging performance. The
      projected size, weight and power advantages, coupled with the manufacturing
      scalability leveraging standard microfabrication technologies, make the Huygens
      meta-optical devices promising for next-generation mid-IR system applications.

PMID- 29662053
TI  - Highly stable graphene-oxide-based membranes with superior permeability.
AB  - Increasing fresh water demand for drinking and agriculture is one of the grand
      challenges of our age. Graphene oxide (GO) membranes have shown a great potential
      for desalination and water purification. However, it is challenging to further
      improve the water permeability without sacrificing the separation efficiency, and
      the GO membranes are easily delaminated in aqueous solutions within few hours.
      Here, we report a class of reduced GO membranes with enlarged interlayer distance
      fabricated by using theanine amino acid and tannic acid as reducing agent and
      cross-linker. Such membranes show water permeance over 10,000 L m-2 h-1 bar-1,
      which is 10-1000 times higher than those of previously reported GO-based
      membranes and commercial membranes, and good separation efficiency, e.g.,
      rhodamine B and methylene blue rejection of ~100%. Moreover, they show no damage
      or delamination in water, acid, and basic solutions even after months.

PMID- 29662054
TI  - Characterising the phenotypic evolution of circulating tumour cells during
      treatment.
AB  - Real-time monitoring of cancer cells' phenotypic evolution during therapy can
      provide vital tumour biology information for treatment management. Circulating
      tumour cell (CTC) analysis has emerged as a useful monitoring tool, but its
      routine usage is restricted by either limited multiplexing capability or
      sensitivity. Here, we demonstrate the use of antibody-conjugated and Raman
      reporter-coated gold nanoparticles for simultaneous labelling and monitoring of
      multiple CTC surface markers (named as "cell signature"), without the need for
      isolating individual CTCs. We observe cell heterogeneity and phenotypic changes
      of melanoma cell lines during molecular targeted treatment. Furthermore, we
      follow the CTC signature changes of 10 stage-IV melanoma patients receiving
      immunological or molecular targeted therapies. Our technique maps the phenotypic
      evolution of patient CTCs sensitively and rapidly, and shows drug-resistant
      clones having different CTC signatures of potential clinical value. We believe
      our proposed method is of general interest in the CTC relevant research and
      translation fields.

PMID- 29662055
TI  - In silico optimization of a guava antimicrobial peptide enables combinatorial
      exploration for peptide design.
AB  - Plants are extensively used in traditional medicine, and several plant
      antimicrobial peptides have been described as potential alternatives to
      conventional antibiotics. However, after more than four decades of research no
      plant antimicrobial peptide is currently used for treating bacterial infections,
      due to their length, post-translational modifications or  high dose requirement
      for a therapeutic effect . Here we report the design of antimicrobial peptides
      derived from a guava glycine-rich peptide using a genetic algorithm. This
      approach yields guavanin peptides, arginine-rich alpha-helical peptides that
      possess an unusual hydrophobic counterpart mainly composed of tyrosine residues.
      Guavanin 2 is characterized as a prototype peptide in terms of structure and
      activity. Nuclear magnetic resonance analysis indicates that the peptide adopts
      an alpha-helical structure in hydrophobic environments. Guavanin 2 is
      bactericidal at low concentrations, causing membrane disruption and triggering
      hyperpolarization. This computational approach for the exploration of natural
      products could be used to design effective peptide antibiotics.

PMID- 29662056
TI  - Neuronal SphK1 acetylates COX2 and contributes to pathogenesis in a model of
      Alzheimer's Disease.
AB  - Although many reports have revealed the importance of defective microglia
      mediated amyloid beta phagocytosis in Alzheimer's disease (AD), the underlying
      mechanism remains to be explored. Here we demonstrate that neurons in the brains
      of patients with AD and AD mice show reduction of sphingosine kinase1 (SphK1),
      leading to defective microglial phagocytosis and dysfunction of inflammation
      resolution due to decreased secretion of specialized proresolving mediators
      (SPMs). Elevation of SphK1 increased SPMs secretion, especially 15-R-Lipoxin A4,
      by promoting acetylation of serine residue 565 (S565) of cyclooxygenase2 (COX2)
      using acetyl-CoA, resulting in improvement of AD-like pathology in APP/PS1 mice.
      In contrast, conditional SphK1 deficiency in neurons reduced SPMs secretion and
      abnormal phagocytosis similar to AD. Together, these results uncover a novel
      mechanism of SphK1 pathogenesis in AD, in which impaired SPMs secretion leads to
      defective microglial phagocytosis, and suggests that SphK1 in neurons has acetyl
      CoA-dependent cytoplasmic acetyltransferase activity towards COX2.

PMID- 29662057
TI  - Quantitative assessment of protein activity in orphan tissues and single cells
      using the metaVIPER algorithm.
AB  - We and others have shown that transition and maintenance of biological states is
      controlled by master regulator proteins, which can be inferred by interrogating
      tissue-specific regulatory models (interactomes) with transcriptional signatures,
      using the VIPER algorithm. Yet, some tissues may lack molecular profiles
      necessary for interactome inference (orphan tissues), or, as for single cells
      isolated from heterogeneous samples, their tissue context may be undetermined. To
      address this problem, we introduce metaVIPER, an algorithm designed to assess
      protein activity in tissue-independent fashion by integrative analysis of
      multiple, non-tissue-matched interactomes. This assumes that transcriptional
      targets of each protein will be recapitulated by one or more available
      interactomes. We confirm the algorithm's value in assessing protein dysregulation
      induced by somatic mutations, as well as in assessing protein activity in orphan
      tissues and, most critically, in single cells, thus allowing transformation of
      noisy and potentially biased RNA-Seq signatures into reproducible protein
      activity signatures.

PMID- 29662058
TI  - Greenland records of aerosol source and atmospheric lifetime changes from the
      Eemian to the Holocene.
AB  - The Northern Hemisphere experienced dramatic changes during the last glacial,
      featuring vast ice sheets and abrupt climate events, while high northern
      latitudes during the last interglacial (Eemian) were warmer than today. Here we
      use high-resolution aerosol records from the Greenland NEEM ice core to
      reconstruct the environmental alterations in aerosol source regions accompanying
      these changes. Separating source and transport effects, we find strongly reduced
      terrestrial biogenic emissions during glacial times reflecting net loss of
      vegetated area in North America. Rapid climate changes during the glacial have
      little effect on terrestrial biogenic aerosol emissions. A strong increase in
      terrestrial dust emissions during the coldest intervals indicates higher aridity
      and dust storm activity in East Asian deserts. Glacial sea salt aerosol emissions
      in the North Atlantic region increase only moderately (50%), likely due to sea
      ice expansion. Lower aerosol concentrations in Eemian ice compared to the
      Holocene are mainly due to shortened atmospheric residence time, while emissions
      changed little.

PMID- 29662060
TI  - Author Correction: Harmonic phase in polar liquids and spin ice.
AB  - The original version of this Article contained an error in the third sentence of
      the penultimate paragraph of the 'Definition of the harmonic phase' section of
      the Results, which incorrectly read 'In the Coulomb phase the tensor S alphabeta
      (q) has one zero and two degenerate eigenvalues and it may be represented by an
      infinitely thin disc of radius 3/2 with its axis parallel to q.' The correct
      version states '[Formula: see text]' in place of '3/2.'Similarly, the second
      sentence in the legend of Fig. 3 originally incorrectly read 'In the Coulomb
      phase it is an infinitely thin disc with radius 3/2, but in the harmonic phase it
      becomes an oblate spheroid, that evolves from the disc in the low-temperature
      limit towards a unit sphere at high temperature (disc and example spheroid shown
      overlaid together).' The correct version states ' [Formula: see text] ' instead
      of '3/2'.This has been corrected in both the PDF and HTML versions of the
      Article.

PMID- 29662059
TI  - Genome-wide association study of depression phenotypes in UK Biobank identifies
      variants in excitatory synaptic pathways.
AB  - Depression is a polygenic trait that causes extensive periods of disability.
      Previous genetic studies have identified common risk variants which have
      progressively increased in number with increasing sample sizes of the respective
      studies. Here, we conduct a genome-wide association study in 322,580 UK Biobank
      participants for three depression-related phenotypes: broad depression, probable
      major depressive disorder (MDD), and International Classification of Diseases
      (ICD, version 9 or 10)-coded MDD. We identify 17 independent loci that are
      significantly associated (P < 5 * 10-8) across the three phenotypes. The
      direction of effect of these loci is consistently replicated in an independent
      sample, with 14 loci likely representing novel findings. Gene sets are enriched
      in excitatory neurotransmission, mechanosensory behaviour, post synapse, neuron
      spine and dendrite functions. Our findings suggest that broad depression is the
      most tractable UK Biobank phenotype for discovering genes and gene sets that
      further our understanding of the biological pathways underlying depression.

PMID- 29662061
TI  - RPAP3 provides a flexible scaffold for coupling HSP90 to the human R2TP co
      chaperone complex.
AB  - The R2TP/Prefoldin-like co-chaperone, in concert with HSP90, facilitates assembly
      and cellular stability of RNA polymerase II, and complexes of PI3-kinase-like
      kinases such as mTOR. However, the mechanism by which this occurs is poorly
      understood. Here we use cryo-EM and biochemical studies on the human R2TP core
      (RUVBL1-RUVBL2-RPAP3-PIH1D1) which reveal the distinctive role of RPAP3,
      distinguishing metazoan R2TP from the smaller yeast equivalent. RPAP3 spans both
      faces of a single RUVBL ring, providing an extended scaffold that recruits
      clients and provides a flexible tether for HSP90. A 3.6 A cryo-EM structure
      reveals direct interaction of a C-terminal domain of RPAP3 and the ATPase domain
      of RUVBL2, necessary for human R2TP assembly but absent from yeast. The mobile
      TPR domains of RPAP3 map to the opposite face of the ring, associating with
      PIH1D1, which mediates client protein recruitment. Thus, RPAP3 provides a
      flexible platform for bringing HSP90 into proximity with diverse client proteins.

PMID- 29662062
TI  - Pausing controls branching between productive and non-productive pathways during
      initial transcription in bacteria.
AB  - Transcription in bacteria is controlled by multiple molecular mechanisms that
      precisely regulate gene expression. It has been recently shown that initial RNA
      synthesis by the bacterial RNA polymerase (RNAP) is interrupted by pauses;
      however, the pausing determinants and the relationship of pausing with productive
      and abortive RNA synthesis remain poorly understood. Using single-molecule FRET
      and biochemical analysis, here we show that the pause encountered by RNAP after
      the synthesis of a 6-nt RNA (ITC6) renders the promoter escape strongly dependent
      on the NTP concentration. Mechanistically, the paused ITC6 acts as a checkpoint
      that directs RNAP to one of three competing pathways: productive transcription,
      abortive RNA release, or a new unscrunching/scrunching pathway. The cyclic
      unscrunching/scrunching of the promoter generates a long-lived, RNA-bound paused
      state; the abortive RNA release and DNA unscrunching are thus not as tightly
      linked as previously thought. Finally, our new model couples the pausing with the
      abortive and productive outcomes of initial transcription.

PMID- 29662063
TI  - Dinosaur diversification linked with the Carnian Pluvial Episode.
AB  - Dinosaurs diversified in two steps during the Triassic. They originated about 245
      Ma, during the recovery from the Permian-Triassic mass extinction, and then
      remained insignificant until they exploded in diversity and ecological importance
      during the Late Triassic. Hitherto, this Late Triassic explosion was poorly
      constrained and poorly dated. Here we provide evidence that it followed the
      Carnian Pluvial Episode (CPE), dated to 234-232 Ma, a time when climates switched
      from arid to humid and back to arid again. Our evidence comes from a combined
      analysis of skeletal evidence and footprint occurrences, and especially from the
      exquisitely dated ichnofaunas of the Italian Dolomites. These provide evidence of
      tetrapod faunal compositions through the Carnian and Norian, and show that
      dinosaur footprints appear exactly at the time of the CPE. We argue then that
      dinosaurs diversified explosively in the mid Carnian, at a time of major climate
      and floral change and the extinction of key herbivores, which the dinosaurs
      opportunistically replaced.

PMID- 29662064
TI  - The use of electronic alerts in primary care computer systems to identify the
      excessive prescription of short-acting beta2-agonists for people with asthma: a
      systematic review.
AB  - Computers are increasingly used to improve prescribing decisions in the
      management of long-term conditions however the effects on asthma prescribing
      remain unclear. We aimed to synthesise the evidence for the use of computerised
      alerts that identify excessive prescribing of short-acting beta2-agonists (SABAs)
      to improve asthma management for people with asthma. MEDLINE, CINAHL, Embase,
      Cochrane and Scopus databases (1990-2016) were searched for randomised controlled
      trials using electronic alerts to identify excessive prescribing of SABAs for
      people with asthma in primary care. Inclusion eligibility, quality appraisal
      (Cochrane risk of bias tool) and data extraction were performed by two
      independent reviewers. Findings were synthesised narratively. A total of 2035
      articles were screened and four trials were eligible. Three studies had low risk
      of bias: one reported a positive effect on our primary outcome of interest,
      excessive SABA prescribing; another reported positive effects on the ratio of
      inhaled corticosteroid (ICS)-SABA prescribing, and asthma control; a third
      reported no effect on outcomes of interest. One study at high risk of bias
      reported a reduction in exacerbations and primary care consultations. There is
      some evidence that electronic alerts reduce excessive prescribing of SABAs, when
      delivered as part of a multicomponent intervention in an integrated health care
      system. However due to the variation in health care systems, intervention design
      and outcomes measured, further research is required to establish optimal design
      of alerting and intervening systems.

PMID- 29662065
TI  - Dripplons as localized and superfast ripples of water confined between graphene
      sheets.
AB  - Carbon materials have unveiled outstanding properties as membranes for water
      transport, both in 1D carbon nanotube and between 2D graphene layers. In the
      ultimate confinement, water properties however strongly deviate from the
      continuum, showing exotic properties with numerous counterparts in fields ranging
      from nanotribology to biology. Here, by means of molecular dynamics, we show a
      self-organized inhomogeneous structure of water confined between graphene sheets,
      whereby the very strong localization of water defeats the energy cost for bending
      the graphene sheets. This leads to a two-dimensional water droplet accompanied by
      localized graphene ripples, which we call "dripplon." Additional osmotic effects
      originating in dissolved impurities are shown to further stabilize the dripplon.
      Our analysis also reveals a counterintuitive superfast dynamics of the dripplons,
      comparable to that of individual water molecules. They move like a (nano-) ruck
      in a rug, with water molecules and carbon atoms exchanging rapidly across the
      dripplon interface.

PMID- 29662066
TI  - Memory effect and magnetocrystalline anisotropy impact on the surface magnetic
      domains of magnetite(001).
AB  - The structure of magnetic domains, i.e. regions of uniform magnetization
      separated by domain walls, depends on the balance of competing interactions
      present in ferromagnetic (or ferrimagnetic) materials. When these interactions
      change then domain configurations also change as a result. Magnetite provides a
      good test bench to study these effects, as its magnetocrystalline anisotropy
      varies significantly with temperature. Using spin-polarized electron microscopy
      to map the micromagnetic domain structure in the (001) surface of a macroscopic
      magnetite crystal (~1 cm size) shows complex domain patterns with characteristic
      length-scales in the micrometer range and highly temperature dependent domain
      geometries. Although heating above the Curie temperature erases the domain
      patterns completely, cooling down reproduces domain patterns not only in terms of
      general characteristics: instead, complex microscopic domain geometries are
      reproduced in almost perfect fidelity between heating cycles. A possible
      explanation of the origin of the high-fidelity reproducibility is suggested to be
      a combination of the presence of hematite inclusions that lock bulk domains,
      together with the strong effect of the first order magnetocrystalline anisotropy
      which competes with the shape anisotropy to give rise to the observed complex
      patterns.

PMID- 29662067
TI  - Author Correction: Radioligand binding analysis of alpha 2 adrenoceptors with
      [11C]yohimbine in brain in vivo: Extended Inhibition Plot correction for plasma
      protein binding.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 29662068
TI  - Incidental haptic sensations influence judgment of crimes.
AB  - Extralegal factors may influence judicial outcomes. Here we investigated the
      experience of incidental haptic sensations on the harshness of punishment
      recommendations. Based on recent theories of embodiment, which claim that
      cognitive representations are structured by metaphorical mappings from sensory
      experience, we hypothesized that tactile priming with hard objects would cause
      subjects to recommend harsher sentences (to be 'hard on crime'). Furthermore, the
      theory of embodiment predicts that this effect should be based on sensorimotor
      brain activation during the judging process. In order to test this we presented
      participants with scenarios that described various crimes while scanning their
      brain activity with fMRI. Participants were then asked to rate how severely they
      would sentence the delinquents. Before the scenarios, the participants were
      primed by touching either a hard or a soft object. Results revealed tha t hard
      priming led participants to recommend harder punishments. These results were
      accompanied by activation of somatosensory brain areas during the judging phase.
      This outcome is in line with simulation assumptions of the embodiment theory and
      proposes a central role of the sensorimotor cortices for embodied metaphors.
      Thus, incidental tactile experiences can influence our abstract cognitions and
      even how hard we are on criminals.

PMID- 29662069
TI  - Author Correction: Antimicrobial activity of Ti-ZrN/Ag coatings for use in
      biomaterial applications.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 29662070
TI  - Systemic and sex-biased regulation of OBP expression under semiochemical stimuli.
AB  - Constitutive expression of Odorant-Binding Proteins (OBPs) in antennae and other
      body parts has been examined mainly to infer their involvement in insect
      olfaction, while their regulation in response to semiochemical stimuli has
      remained poorly known. Previous studies of semiochemical response were basically
      done using electrophysiology, which integrates the response of the set of OBPs
      present in an antenna or sensillum, without revealing the regulation of OBPs or
      which ones might be involved. In this study we used boll weevil as a model and
      mined its OBPs by RNA-Seq to study their simultaneous antennal expression by qPCR
      under controlled semiochemical stimuli with aggregation pheromone and plant
      volatiles. In the absence of a semiochemical stimulus, 23 of 24 OBPs were
      constitutively expressed in the antenna in both sexes. Semiochemicals changed
      systemically the expression of OBPs in both sexes. There were different patterns
      of up- and down-regulation in female antennae for each semiochemical stimulus,
      consistent with female chemical ecology. On the other hand, the only response in
      males was down-regulation of some OBPs. We suggest that these systemic changes in
      OBP expression might be related to enhancing detection of the semiochemical
      stimuli and/or priming the olfactory system to detect other environmental
      chemicals.

PMID- 29662072
TI  - A Firefly Luciferase Dual Color Bioluminescence Reporter Assay Using Two
      Substrates To Simultaneously Monitor Two Gene Expression Events.
AB  - Effective methods for monitoring eukaryotic gene expression and regulation based
      on bioluminescence - the emission of light by living organisms - are well
      established. Typically, the expression of a gene of interest is reported on with
      high sensitivity and over a wide dynamic range by the emission of light from a
      variety of engineered luciferase genes from beetles and marine organisms. The
      luciferase reporter genes are expressed downstream of the target gene or promoter
      and detected after exogenous addition of luciferin substrates. We describe a
      novel bioluminescence reporter method for the simultaneous monitoring of two
      genes expressing engineered firefly luciferase variants that emit readily
      distinguishable green and red light signals. The key feature is the selectivity
      of the enzymes for two luciferin substrates that determine each emission color.
      To validate our method, we performed a complex promoter transactivation
      experiment side-by-side with the Dual-Luciferase Reporter protocol and obtained
      essentially identical results. Additional comparative experiments demonstrated
      that our assay system provided improvements in background, cell normalization,
      and detectability compared to representative available methods. With access to a
      luminometer equipped with two optical filters, this method is an excellent choice
      for genetic reporter assays that can be performed with a single reagent solution.

PMID- 29662073
TI  - Global warming hiatus contributed to the increased occurrence of intense tropical
      cyclones in the coastal regions along East Asia.
AB  - The recent global warming hiatus (GWH) was characterized by a La Nina-like
      cooling in the tropical Eastern Pacific accompanied with the Indian Ocean and the
      tropical Atlantic Ocean warming. Here we show that the recent GWH contributed
      significantly to the increased occurrence of intense tropical cyclones in the
      coastal regions along East Asia since 1998. The GWH associated sea surface
      temperature anomalies triggered a pair of anomalous cyclonic and anticyclonic
      circulations and equatorial easterly anomalies over the Northwest Pacific, which
      favored TC genesis and intensification over the western Northwest Pacific but
      suppressed TC genesis and intensification over the southeastern Northwest Pacific
      due to increased vertical wind shear and anticyclonic circulation anomalies.
      Results from atmospheric general circulation model experiments demonstrate that
      the Pacific La Nina-like cooling dominated the Indian Ocean and the tropical
      Atlantic Ocean warming in contributing to the observed GWH-related anomalous
      atmospheric circulation over the Northwest Pacific.

PMID- 29662071
TI  - LRH-1 agonism favours an immune-islet dialogue which protects against diabetes
      mellitus.
AB  - Type 1 diabetes mellitus (T1DM) is due to the selective destruction of islet beta
      cells by immune cells. Current therapies focused on repressing the immune attack
      or stimulating beta cell regeneration still have limited clinical efficacy.
      Therefore, it is timely to identify innovative targets to dampen the immune
      process, while promoting beta cell survival and function. Liver receptor
      homologue-1 (LRH-1) is a nuclear receptor that represses inflammation in
      digestive organs, and protects pancreatic islets against apoptosis. Here, we show
      that BL001, a small LRH-1 agonist, impedes hyperglycemia progression and the
      immune-dependent inflammation of pancreas in murine models of T1DM, and beta cell
      apoptosis in islets of type 2 diabetic patients, while increasing beta cell mass
      and insulin secretion. Thus, we suggest that LRH-1 agonism favors a dialogue
      between immune and islet cells, which could be druggable to protect against
      diabetes mellitus.

PMID- 29662074
TI  - Competition between microtubule-associated proteins directs motor transport.
AB  - Within cells, motor and non-motor microtubule-associated proteins (MAPs)
      simultaneously converge on the microtubule. How the binding activities of non
      motor MAPs are coordinated and how they contribute to the balance and
      distribution of motor transport is unknown. Here, we examine the relationship
      between MAP7 and tau owing to their antagonistic roles in vivo. We find that MAP7
      and tau compete for binding to microtubules, and determine a mechanism by which
      MAP7 displaces tau from the lattice. MAP7 promotes kinesin-based transport in
      vivo and strongly recruits kinesin-1 to the microtubule in vitro, providing
      evidence for direct enhancement of motor motility by a MAP. Both MAP7 and tau
      strongly inhibit kinesin-3 and have no effect on cytoplasmic dynein,
      demonstrating that MAPs differentially control distinct classes of motors.
      Overall, these results reveal a general principle for how MAP competition
      dictates access to the microtubule to determine the correct distribution and
      balance of motor activity.

PMID- 29662075
TI  - The unique functioning of a pre-Columbian Amazonian floodplain fishery.
AB  - Archaeology provides few examples of large-scale fisheries at the frontier
      between catching and farming of fish. We analysed the spatial organization of
      earthen embankments to infer the functioning of a landscape-level pre-Columbian
      Amazonian fishery that was based on capture of out-migrating fish after
      reproduction in seasonal floodplains. Long earthen weirs cross floodplains. We
      showed that weirs bear successive V-shaped features (termed 'Vs' for the sake of
      brevity) pointing downstream for outflowing water and that ponds are associated
      with Vs, the V often forming the pond's downstream wall. How Vs channelled fish
      into ponds cannot be explained simply by hydraulics, because Vs surprisingly lack
      fishways, where, in other weirs, traps capture fish borne by current flowing
      through these gaps. We suggest that when water was still high enough to flow over
      the weir, out-migrating bottom-hugging fish followed current downstream into Vs.
      Finding deeper, slower-moving water, they remained. Receding water further
      concentrated fish in ponds. The pond served as the trap, and this function shaped
      pond design. Weir-fishing and pond-fishing are both practiced in African
      floodplains today. In combining the two, this pre-Columbian system appears unique
      in the world.

PMID- 29662076
TI  - A RAB35-p85/PI3K axis controls oscillatory apical protrusions required for
      efficient chemotactic migration.
AB  - How cells move chemotactically remains a major unmet challenge in cell biology.
      Emerging evidence indicates that for interpreting noisy, shallow gradients of
      soluble cues a system must behave as an excitable process. Here, through an RNAi
      based, high-content screening approach, we identify RAB35 as necessary for the
      formation of growth factors (GFs)-induced waves of circular dorsal ruffles
      (CDRs), apically restricted actin-rich migratory protrusions. RAB35 is sufficient
      to induce recurrent and polarized CDRs that travel as propagating waves, thus
      behaving as an excitable system that can be biased to control cell steering.
      Consistently, RAB35 is essential for promoting directed chemotactic migration and
      chemoinvasion of various cells in response to gradients of motogenic GFs.
      Molecularly, RAB35 does so by directly regulating the activity of p85/PI3K
      polarity axis. We propose that RAB35 is a molecular determinant for the control
      of an excitable, oscillatory system that acts as a steering wheel for GF-mediated
      chemotaxis and chemoinvasion.

PMID- 29662077
TI  - Pharmacodynamics of mutant-IDH1 inhibitors in glioma patients probed by in vivo
      3D MRS imaging of 2-hydroxyglutarate.
AB  - Inhibitors of the mutant isocitrate dehydrogenase 1 (IDH1) entered recently in
      clinical trials for glioma treatment. Mutant IDH1 produces high levels of 2
      hydroxyglurate (2HG), thought to initiate oncogenesis through epigenetic
      modifications of gene expression. In this study, we show the initial evidence of
      the pharmacodynamics of a new mutant IDH1 inhibitor in glioma patients, using non
      invasive 3D MR spectroscopic imaging of 2HG. Our results from a Phase 1 clinical
      trial indicate a rapid decrease of 2HG levels by 70% (CI 13%, P = 0.019) after 1
      week of treatment. Importantly, inhibition of mutant IDH1 may lead to the
      reprogramming of tumor metabolism, suggested by simultaneous changes in
      glutathione, glutamine, glutamate, and lactate. An inverse correlation between
      metabolic changes and diffusion MRI indicates an effect on the tumor-cell
      density. We demonstrate a feasible radiopharmacodynamics approach to support the
      rapid clinical translation of rationally designed drugs targeting IDH1/2
      mutations for personalized and precision medicine of glioma patients.

PMID- 29662078
TI  - Comparison of the life-history parameters and competition outcome with Moina
      macrocopa between two morphs of Brachionus forficula.
AB  - In rotifers, the costs of morphological defenses, especially the development of
      long spines, have been investigated for several decades. However, the obtained
      results were inconsistent and the underlying reasons were complicated.
      Investigations on more species might be helpful to find out the reasons. In the
      present study, Brachionus forficula was selected as the model organism. The
      differences in developmental durations, life-table demography, starvation
      resistant time and the competitive ability with Moina macrocopa were compared
      between B. forficula with long (LPS) and short (SPS) posterior spines. The
      results showed that LPS showed relatively longer durations of juvenile stage at
      1.0 * 106, 2.0 * 106 and 4.0 * 106 cells/ml Scenedesmus obliquus, and longer
      embryo stage at 2.0 * 106 cells/ml S. obliquus than SPS. The intrinsic rate of
      population increase and net reproduction rate were lower in LPS than SPS,
      suggesting the energy input to reproduction decreased. The starvation resistant
      time was also reduced in LPS, in comparison to SPS, further supporting that LPS
      consumed more energy, which might be directed to the development of long spines.
      All these results revealed that LPS spent more energy for individual growth than
      SPS, which might be used to develop long spines. Moreover, the maximum population
      density and population growth rate of LPS were always lower than those of SPS,
      suggesting that LPS might have a weaker competition ability with M. macrocope
      than SPS.

PMID- 29662079
TI  - Author Correction: New insights into gelatinization mechanisms of cereal
      endosperm starches.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 29662080
TI  - Involvement of AMP-activated Protein Kinase (AMPK) in Regulation of Cell Membrane
      Potential in a Gastric Cancer Cell Line.
AB  - Membrane potential (Vmem) is a key bioelectric property of non-excitable cells
      that plays important roles in regulating cell proliferation. However, the
      regulation of Vmem itself remains largely unexplored. We found that, under
      nutrient starvation, during which cell division is inhibited, MKN45 gastric
      cancer cells were in a hyperpolarized state associated with a high intracellular
      chloride concentration. AMP-activated protein kinase (AMPK) activity increased,
      and expression of cystic fibrosis transmembrane conductance regulator (CFTR)
      decreased, in nutrient-starved cells. Furthermore, the increase in intracellular
      chloride concentration level and Vmem hyperpolarization in nutrient-starved cells
      was suppressed by inhibition of AMPK activity. Intracellular chloride
      concentrations and hyperpolarization increased after over-activation of AMPK
      using the specific activator AICAR or suppression of CFTR activity using specific
      inhibitor GlyH-101. Under these conditions, proliferation of MKN45 cells was
      inhibited. These results reveal that AMPK controls the dynamic change in Vmem by
      regulating CFTR and influencing the intracellular chloride concentration, which
      in turn influences cell-cycle progression. These findings offer new insights into
      the mechanisms underlying cell-cycle arrest regulated by AMPK and CFTR.

PMID- 29662081
TI  - A quantitative LumiFluo assay to test inhibitory compounds blocking p53
      degradation induced by human papillomavirus oncoprotein E6 in living cells.
AB  - High-risk human papillomaviruses (HR-HPVs) are the causative agents for the onset
      of several epithelial cancers in humans. The deregulated expression of the viral
      oncoproteins E6 and E7 is the driving force sustaining the progression of
      malignant transformation in pre-neoplastic lesions. Targeting the viral E6
      oncoprotein through inhibitory compounds can counteract the survival of cancer
      cells due to the reactivation of p53-mediated pathways and represents an
      intriguing strategy to treat HPV-associated neoplasias. Here, we describe the
      development of a quantitative and easy-to-perform assay to monitor the E6
      mediated degradation of p53 in living cells to be used for small-molecule
      testing. This assay allows to unbiasedly determine whether a compound can protect
      p53 from the E6-mediated degradation in cells, through a simple 3-step protocol.
      We validated the assay by testing two small molecules, SAHA and RITA, reported to
      impair the E6-mediated p53 degradation. Interestingly, we observed that only SAHA
      efficiently rescued p53, while RITA could not provide the same degree of
      protection. The possibility to specifically and quantitatively monitor the
      ability of a selected compound to rescue p53 in a cellular context through our
      LumiFluo assay could represent an important step towards the successful
      development of anti-HPV drugs.

PMID- 29662082
TI  - HadD, a novel fatty acid synthase type II protein, is essential for alpha- and
      epoxy-mycolic acid biosynthesis and mycobacterial fitness.
AB  - Mycolic acids (MAs) have a strategic location within the mycobacterial envelope,
      deeply influencing its architecture and permeability, and play a determinant role
      in the pathogenicity of mycobacteria. The fatty acid synthase type II (FAS-II)
      multienzyme system is involved in their biosynthesis. A combination of pull-downs
      and proteomics analyses led to the discovery of a mycobacterial protein, HadD,
      displaying highly specific interactions with the dehydratase HadAB of FAS-II. In
      vitro activity assays and homology modeling showed that HadD is, like HadAB, a
      hot dog folded (R)-specific hydratase/dehydratase. A hadD knockout mutant of
      Mycobacterium smegmatis produced only the medium-size alpha'-MAs. Data strongly
      suggest that HadD is involved in building the third meromycolic segment during
      the late FAS-II elongation cycles, leading to the synthesis of the full-size
      alpha- and epoxy-MAs. The change in the envelope composition induced by hadD
      inactivation strongly altered the bacterial fitness and capacities to aggregate,
      assemble into colonies or biofilms and spread by sliding motility, and conferred
      a hypersensitivity to the firstline antimycobacterial drug rifampicin. This
      showed that the cell surface properties and the envelope integrity were greatly
      affected. With the alarmingly increasing case number of nontuberculous
      mycobacterial diseases, HadD appears as an attractive target for drug
      development.

PMID- 29662083
TI  - Mechanical Tension Drives Elongational Growth of the Embryonic Gut.
AB  - During embryonic development, most organs are in a state of mechanical
      compression because they grow in a confined and limited amount of space within
      the embryo's body; the early gut is an exception because it physiologically
      herniates out of the coelom. We demonstrate here that physiological hernia is
      caused by a tensile force transmitted by the vitelline duct on the early gut loop
      at its attachment point at the umbilicus. We quantify this tensile force and show
      that applying tension for 48 h induces stress-dependent elongational growth of
      the embryonic gut in culture, with an average 90% length increase (max: 200%),
      65% volume increase (max: 160%), 50% dry mass increase (max: 100%), and 165% cell
      number increase (max: 300%); this mechanical cue is required for organ growth as
      guts not subject to tension do not grow. We demonstrate that growth results from
      increased cell proliferation when tension is applied. These results outline the
      essential role played by mechanical forces in shaping and driving the
      proliferation of embryonic organs.

PMID- 29662084
TI  - HOXA9 inhibits HIF-1alpha-mediated glycolysis through interacting with CRIP2 to
      repress cutaneous squamous cell carcinoma development.
AB  - Glycolytic reprogramming is a typical feature of many cancers; however, key
      regulators of glucose metabolism reengineering are poorly understood, especially
      in cutaneous squamous cell carcinoma (cSCC). Here, Homeobox A9 (HOXA9), a direct
      target of onco-miR-365, is identified to be significantly downregulated in cSCC
      tumors and cell lines. HOXA9 acts as a tumor suppressor and inhibits glycolysis
      in cSCC in vitro and in vivo by negatively regulating HIF-1alpha and its
      downstream glycolytic regulators, HK2, GLUT1 and PDK1. Mechanistic studies show
      that HOXA9-CRIP2 interaction at glycolytic gene promoters impeds HIF-1alpha
      binding, repressing gene expression in trans. Our results reveal a miR-365-HOXA9
      HIF-1alpha regulatory axis that contributes to the enhanced glycolysis in cSCC
      development and may represent an intervention target for cSCC therapy.

PMID- 29662085
TI  - Different methods of methyl eugenol application enhance the mating success of
      male Oriental fruit fly (Dipera: Tephritidae).
AB  - Males of Bactrocera dorsalis (Hendel) (Diptera: Tephritidae) are strongly
      attracted to methyl eugenol (ME) (1,2-dimethoxy-4-(2-propenyl)benzene), a
      phenylpropanoid compound occurring in many plant species. Feeding on ME is known
      to enhance male B. dorsalis mating competitiveness, which can increase the
      effectiveness of the sterile insect technique (SIT) manifold. However, currently
      used systems for holding the mass-reared males in fly emergence and release
      facilities before release, do not allow for application of ME through feeding.
      Therefore, the current study was designed to evaluate different delivery systems
      of ME that would be applicable for large-scale application to sterile males held
      in such facilities. Males of a genetic sexing strain (GSS) of B. dorsalis treated
      by ME-aromatherapy or ME-airblown-aromatherapy that were competing with ME-fed
      males achieved a similar level of mating success in walk-in field cages, but the
      mating success was significantly higher when compared to untreated males. The
      results confirm the feasibility of developing ME-airblown-aromatherapy as a
      practical way of large scale ME delivery to enhance the mating competitiveness of
      sterile B. dorsalis males.

PMID- 29662086
TI  - Persistence of the ABCC6 genes and the emergence of the bony skeleton in
      vertebrates.
AB  - The ATP-binding cassette transporter 6 (ABCC6) gene encodes a cellular
      transmembrane protein transporter (MRP6) that is involved in the regulation of
      tissue calcification in mammals. Mutations in ABCC6 are associated with human
      ectopic calcification disorders. To gain insight into its evolution and
      involvement in tissue calcification we conducted a comparative analysis of the
      ABCC6 gene and the related gene ABCC1 from invertebrates to vertebrates where a
      bony endoskeleton first evolved. Taking into consideration the role of ABCC6 in
      ectopic calcification of human skin we analysed the involvement of both genes in
      the regeneration of scales, mineralized structures that develop in fish skin. The
      ABCC6 gene was only found in bony vertebrate genomes and was absent from
      Elasmobranchs, Agnatha and from invertebrates. In teleost fish the abcc6 gene
      duplicated but the two genes persisted only in some teleost genomes. Six disease
      causing amino acid mutations in human MRP6 are a normal feature of abcc6 in fish,
      suggesting they do not have a deleterious effect on the protein. After scale
      removal the abcc6 (5 and 10 days) and abcc1 (10 days) gene expression was up
      regulated relative to the intact control skin and this coincided with a time of
      intense scale mineralization.

PMID- 29662087
TI  - Accurate identification of RNA editing sites from primitive sequence with deep
      neural networks.
AB  - RNA editing is a post-transcriptional RNA sequence alteration. Current methods
      have identified editing sites and facilitated research but require sufficient
      genomic annotations and prior-knowledge-based filtering steps, resulting in a
      cumbersome, time-consuming identification process. Moreover, these methods have
      limited generalizability and applicability in species with insufficient genomic
      annotations or in conditions of limited prior knowledge. We developed DeepRed, a
      deep learning-based method that identifies RNA editing from primitive RNA
      sequences without prior-knowledge-based filtering steps or genomic annotations.
      DeepRed achieved 98.1% and 97.9% area under the curve (AUC) in training and test
      sets, respectively. We further validated DeepRed using experimentally verified
      U87 cell RNA-seq data, achieving 97.9% positive predictive value (PPV). We
      demonstrated that DeepRed offers better prediction accuracy and computational
      efficiency than current methods with large-scale, mass RNA-seq data. We used
      DeepRed to assess the impact of multiple factors on editing identification with
      RNA-seq data from the Association of Biomolecular Resource Facilities and
      Sequencing Quality Control projects. We explored developmental RNA editing
      pattern changes during human early embryogenesis and evolutionary patterns in
      Drosophila species and the primate lineage using DeepRed. Our work illustrates
      DeepRed's state-of-the-art performance; it may decipher the hidden principles
      behind RNA editing, making editing detection convenient and effective.

PMID- 29662088
TI  - Tracing of the fecal microbiota of commercial pigs at five growth stages from
      birth to shipment.
AB  - The intestinal microbiota affect various physiological traits of host animals
      such as brain development, obesity, age, and the immune system. In the swine
      industry, understanding the relationship between intestinal microbiota and growth
      stage is essential because growth stage is directly related to the feeding system
      of pigs, thus we studied the intestinal microbiota of 32 healthy pigs across five
      sows at 10, 21, 63, 93, and 147 d of ages. The intestinal microbiota were altered
      with growth of pigs and were separated into three distinct clusters. The relative
      abundance of several phyla and genera were significantly different between growth
      stages. We observed co-occurrence pattern of the intestinal microbiota at each
      growth stage. In addition, we predicted the functions of the intestinal
      microbiota and confirmed that several KEGG pathways were significantly different
      between growth stages. We also explored the relationship between the intestinal
      microbiota and innate factors such as the maternal effect and gender. When pigs
      were young, innate factors affected on construction of intestinal microbiota,
      however this tendency was disappeared with growth. Our findings broaden the
      understanding of microbial ecology, and the results will be used as a reference
      for investigating host-microbe interactions in the swine industry.

PMID- 29662089
TI  - Time rescaling reproduces EEG behavior during transition from propofol anesthesia
      induced unconsciousness to consciousness.
AB  - General anesthesia (GA) is a reversible manipulation of consciousness whose
      mechanism is mysterious at the level of neural networks leaving space for several
      competing hypotheses. We recorded electrocorticography (ECoG) signals in patients
      who underwent intracranial monitoring during awake surgery for the treatment of
      cerebral tumors in functional areas of the brain. Therefore, we recorded the
      transition from unconsciousness to consciousness directly on the brain surface.
      Using frequency resolved interferometry; we studied the intermediate ECoG
      frequencies (4-40 Hz). In the theoretical study, we used a computational Jansen
      and Rit neuron model to simulate recovery of consciousness (ROC). During ROC, we
      found that f increased by a factor equal to 1.62 +/- 0.09, and deltaf varied by
      the same factor (1.61 +/- 0.09) suggesting the existence of a scaling factor. We
      accelerated the time course of an unconscious EEG trace by an approximate factor
      1.6 and we showed that the resulting EEG trace match the conscious state. Using
      the theoretical model, we successfully reproduced this behavior. We show that the
      recovery of consciousness corresponds to a transition in the frequency (f,
      deltaf) space, which is exactly reproduced by a simple time rescaling. These
      findings may perhaps be applied to other altered consciousness states.

PMID- 29662091
TI  - Asymmetric wave transmission through one dimensional lattices with cubic-quintic
      nonlinearity.
AB  - One dimensional lattice with an on-site cubic-quintic nonlinear response
      described by a cubic-quintic discrete nonlinear Schrodinger equation is tested
      for asymmetric wave propagation. The lattice is connected to linear side chains.
      Asymmetry is introduced by breaking the mirror symmetry of the lattice with
      respect to the center of the nonlinear region. Three cases corresponding to
      dimer, trimer and quadrimer are discussed with focus on the corresponding diode
      like effect. Transmission coefficients are analytically calculated for left and
      right moving waves via backward transfer map. The different transmission
      coefficients for the left and right moving waves impinging the lattice give rise
      to a diode-like effect which is tested for different variations in asymmetry and
      site dependent coefficients. We show that there is a higher transmission for
      incoming waves with lower wavenumbers as compared to the waves with comparatively
      larger wavenumbers and a diode-like effect improves by increasing the nonlinear
      layers. We also show that in the context of transport through such lattices, the
      cooperation between cubic and quintic nonlinear response is not "additive".
      Finally, we numerically analyse Gaussian wave packet dynamics impinging on the
      CQDNLS lattice for all three cases.

PMID- 29662090
TI  - Optical interrogation of neuronal circuitry in zebrafish using genetically
      encoded voltage indicators.
AB  - Optical measurement of membrane potentials enables fast, direct and simultaneous
      detection of membrane potentials from a population of neurons, providing a
      desirable approach for functional analysis of neuronal circuits. Here, we applied
      recently developed genetically encoded voltage indicators, ASAP1 (Accelerated
      Sensor of Action Potentials 1) and QuasAr2 (Quality superior to Arch 2), to
      zebrafish, an ideal model system for studying neurogenesis. To achieve this, we
      established transgenic lines which express the voltage sensors, and showed that
      ASAP1 is expressed in zebrafish neurons. To examine whether neuronal activity
      could be detected by ASAP1, we performed whole-cerebellum imaging, showing that
      depolarization was detected widely in the cerebellum and optic tectum upon
      electrical stimulation. Spontaneous activity in the spinal cord was also detected
      by ASAP1 imaging at single-cell resolution as well as at the neuronal population
      level. These responses mostly disappeared following treatment with tetrodotoxin,
      indicating that ASAP1 enabled optical measurement of neuronal activity in the
      zebrafish brain. Combining this method with other approaches, such as
      optogenetics and behavioural analysis may facilitate a deeper understanding of
      the functional organization of brain circuitry and its development.

PMID- 29662092
TI  - Diffusion-Limited Growth of Microbial Colonies.
AB  - The emergence of diffusion-limited growth (DLG) within a microbial colony on a
      solid substrate is studied using a combination of mathematical modelling and
      experiments. Using an agent-based model of the interaction between microbial
      cells and a diffusing nutrient, it is shown that growth directed towards a
      nutrient source may be used as an indicator that DLG is influencing the colony
      morphology. A continuous reaction-diffusion model for microbial growth is
      employed to identify the parameter regime in which DLG is expected to arise.
      Comparisons between the model and experimental data are used to argue that the
      bacterium Bacillus subtilis can undergo DLG, while the yeast Saccharomyces
      cerevisiae cannot, and thus the non-uniform growth exhibited by this yeast must
      be caused by the pseudohyphal growth mode rather than limited nutrient
      availability. Experiments testing directly for DLG features in yeast colonies are
      used to confirm this hypothesis.

PMID- 29662093
TI  - Application of interspecific Somatic Cell Nuclear Transfer (iSCNT) in sturgeons
      and an unexpectedly produced gynogenetic sterlet with homozygous quadruple
      haploid.
AB  - Somatic cell nuclear transfer (SCNT) is a very promising cloning technique for
      reconstruction of endangered animals. The aim of the present research is to
      implement the interspecific SCNT (iSCNT) technique to sturgeon; one fish family
      bearing some of the most critically endangered species. We transplanted single
      cells enzymatically isolated from a dissociated fin-fragment of the Russian
      sturgeon (Acipenser gueldenstaedtii) into non-enucleated eggs of the sterlet
      (Acipenser ruthenus), two species bearing different ploidy (4n and 2n,
      respectively). Up to 6.7% of the transplanted eggs underwent early development,
      and one feeding larva (0.5%) was successfully produced. Interestingly, although
      this transplant displayed tetraploidism (4n) as the donor species, the
      microsatellite and species-specific analysis showed recipient-exclusive
      homozygosis without any donor markers. Namely, with regards to this viable larva,
      host genome duplication occurred twice to form tetraploidism during its early
      development, probably due to iSCNT manipulation. The importance of this first
      attempt is to apply iSCNT in sturgeon species, establishing the crucial first
      steps by adjusting the cloning-methodology in sturgeon's biology. Future
      improvements in sturgeon's cloning are necessary for providing with great hope in
      sturgeon's reproduction.

PMID- 29662094
TI  - Author Correction: Whole genome diversity of inherited chromosomally integrated
      HHV-6 derived from healthy individuals of diverse geographic origin.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 29662095
TI  - MU-opioid receptor system mediates reward processing in humans.
AB  - The endogenous MU-opioid receptor (MOR) system regulates motivational and hedonic
      processing. We tested directly whether individual differences in MOR are
      associated with neural reward responses to food pictures in humans. We scanned 33
      non-obese individuals with positron emission tomography (PET) using the MOR
      specific radioligand [11C]carfentanil. During a functional magnetic resonance
      imaging (fMRI) scan, the subjects viewed pictures of appetizing versus bland
      foods to elicit reward responses. MOR availability was measured in key components
      of the reward and emotion circuits and used to predict BOLD-fMRI responses to
      foods. Viewing palatable versus bland foods activates regions involved in
      homeostatic and reward processing, such as amygdala, ventral striatum, and
      hypothalamus. MOR availability in the reward and emotion circuit is negatively
      associated with the fMRI reward responses. Variation in MOR availability may
      explain why some people feel an urge to eat when encountering food cues,
      increasing risk for weight gain and obesity.

PMID- 29662097
TI  - Microfabricated electrodes unravel the role of interfaces in multicomponent
      copper-based CO2 reduction catalysts.
AB  - The emergence of synergistic effects in multicomponent catalysts can result in
      breakthrough advances in the electrochemical reduction of carbon dioxide. Copper
      indium catalysts show high performance toward carbon monoxide production but also
      extensive structural and compositional changes under operation. The origin of the
      synergistic effect and the nature of the active phase are not well understood,
      thus hindering optimization efforts. Here we develop a platform that sheds light
      into these aspects, based on microfabricated model electrodes that are evaluated
      under conventional experimental conditions. The relationship among the electrode
      performance, geometry and composition associates the high carbon monoxide
      evolution activity of copper-indium catalysts to indium-poor bimetallic phases,
      which are formed upon exposure to reaction conditions in the vicinity of the
      interfaces between copper oxide and an indium source. The exploratory extension
      of this approach to the copper-tin system demonstrates its versatility and
      potential for the study of complex multicomponent electrocatalysts.

PMID- 29662096
TI  - Variation in Wolbachia effects on Aedes mosquitoes as a determinant of
      invasiveness and vectorial capacity.
AB  - Wolbachia has been introduced into Aedes aegypti mosquitoes to control the spread
      of arboviruses, such as dengue, chikungunya and Zika. Studies showed that certain
      Wolbachia strains (such as wMel) reduce replication of dengue viruses in the
      laboratory, prompting the release of mosquitoes carrying the bacterium into the
      field, where vectorial capacity can be realistically assessed in relation to
      native non-carriers. Here we apply a new analysis to two published datasets, and
      show that wMel increases the mean and the variance in Ae. aegypti susceptibility
      to dengue infection when introgressed into Brazil and Vietnam genetic
      backgrounds. In the absence of other processes, higher mean susceptibility should
      lead to enhanced viral transmission. The increase in variance, however, widens
      the basis for selection imposed by unexplored natural forces, retaining the
      potential for reducing transmission overall.

PMID- 29662098
TI  - Author Correction: Sex differences in the C57BL/6 model of Mycobacterium
      tuberculosis infection.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 29662099
TI  - Lignin peroxidase ligand access channel dysfunction in the presence of atrazine.
AB  - Studies have determined that the white-rot basidiomycete Phanerochaete
      chrysosporium is capable of biodegrading the atrazine herbicide with its broad
      specificity enzymes, but the particular role of biocatalysts is still unclear. In
      the case of lignin peroxidase, a ligand access channel connected to the active
      heme cofactor provides access to the active site for potential small-sized
      substrates. Experimental results show that lignin peroxidase is unable to degrade
      atrazine, therefore, the primary goal was to determine whether there is any
      connection between the structural and dynamical properties of the enzyme and its
      incapability to degrade atrazine. The results of protein-ligand docking and
      molecular dynamics study correlate with relevant, published NMR and molecular
      dynamics data, and give the answer to the lack of atrazine degradation by lignin
      peroxidase which has already been established by numerous authors using
      experimental methods. Atrazine has no access to heme edge due to the electric
      charges of the delocalized s-triazine ring. The detected phenomenon suggests that
      the small size of the ligands only is not a sufficient condition to access the
      active site. Their physicochemical properties influence the structural behaviour
      of the channel.

PMID- 29662100
TI  - Mean platelet volume predicts survival in pancreatic cancer patients with
      synchronous liver metastases.
AB  - Most pancreatic cancer (PC) patients manifest multiple liver metastases at the
      time of diagnosis. Activated platelets play a key role in tumor growth and tumor
      metastases. Mean platelet volume (MPV) is a platelet index and is altered in
      patients with malignancies. This study aimed to evaluate whether MPV can
      effectively predict death in PC patients with synchronous liver metastases. The
      clinical data of 411 PC patients with synchronous liver metastases between
      January 1, 2006 and December 31, 2013 were retrospectively analyzed. Subjects
      were divided into two groups by MPV levels. Clinicopathological data were
      collected retrospectively and relationships between MPV levels and clinical
      parameters were evaluated. Survival analysis was performed. Increased MPV was not
      significantly correlated with tumor location, tumor size, and CA19.9. The Kaplan
      Meier analysis showed that the overall survival of patients with MPV > 8.7 fL was
      significantly shorter than that of those with MPV <= 8.7 fL (log-rank p < 0.001).
      Multivariable Cox proportional hazards model identified MPV as an independent
      poor prognostic factor for overall survival. In conclusion, elevated MPV is
      associated with worse survival outcome in PC patients with synchronous liver
      metastases. Further studies are warranted.

PMID- 29662101
TI  - Gymnosperms on the EDGE.
AB  - Driven by limited resources and a sense of urgency, the prioritization of species
      for conservation has been a persistent concern in conservation science.
      Gymnosperms (comprising ginkgo, conifers, cycads, and gnetophytes) are one of the
      most threatened groups of living organisms, with 40% of the species at high risk
      of extinction, about twice as many as the most recent estimates for all plants
      (i.e. 21.4%). This high proportion of species facing extinction highlights the
      urgent action required to secure their future through an objective prioritization
      approach. The Evolutionary Distinct and Globally Endangered (EDGE) method rapidly
      ranks species based on their evolutionary distinctiveness and the extinction
      risks they face. EDGE is applied to gymnosperms using a phylogenetic tree
      comprising DNA sequence data for 85% of gymnosperm species (923 out of 1090
      species), to which the 167 missing species were added, and IUCN Red List
      assessments available for 92% of species. The effect of different extinction
      probability transformations and the handling of IUCN data deficient species on
      the resulting rankings is investigated. Although top entries in our ranking
      comprise species that were expected to score well (e.g. Wollemia nobilis, Ginkgo
      biloba), many were unexpected (e.g. Araucaria araucana). These results highlight
      the necessity of using approaches that integrate evolutionary information in
      conservation science.

PMID- 29662103
TI  - Authority, Psychotherapy and the Authority of the Therapist in the Religious
      Haredi Community.
AB  - This article considers the meaning and significance of authority, and its
      relevance to the transference process, within the framework of psychotherapy in
      the orthodox Jewish (Haredi) community in Israel. In this community, deeply
      rooted habits of obedience to the commandments of the Torah and the authority of
      the Rabbi are integral to maintaining an orthodox way of life. Clinical vignettes
      with Haredi patients are presented to illustrate the complexities that arise when
      both patient and therapist belong to the orthodox community, and highlight the
      authority-related issues that are central to the therapy. This combination of
      factors requires a sensitive and finely-tuned approach which will enable the
      therapist to maintain the treatment framework while still accommodating the
      orthodox way of life.

PMID- 29662104
TI  - The local and global climate forcings induced inhomogeneity of Indian rainfall.
AB  - India is home for more than a billion people and its economy is largely based on
      agrarian society. Therefore, rainfall received not only decides its livelihood,
      but also influences its water security and economy. This situation warrants
      continuous surveillance and analysis of Indian rainfall. These kinds of studies
      would also help forecasters to better tune their models for accurate weather
      prediction. Here, we introduce a new method for estimating variability and trends
      in rainfall over different climate regions of India. The method based on multiple
      linear regression helps to assess contributions of different remote and local
      climate forcings to seasonal and regional inhomogeneity in rainfall. We show that
      the Indian Summer Monsoon Rainfall (ISMR) variability is governed by Eastern and
      Central Pacific El Nino Southern Oscillation, equatorial zonal winds, Atlantic
      zonal mode and surface temperatures of the Arabian Sea and Bay of Bengal, and the
      North East Monsoon Rainfall variability is controlled by the sea surface
      temperature of the North Atlantic and extratropial oceans. Also, our analyses
      reveal significant positive trends (0.43 mm/day/dec) in the North West for ISMR
      in the 1979-2017 period. This study cautions against the significant changes in
      Indian rainfall in a perspective of global climate change.

PMID- 29662105
TI  - New insight and metrics to understand the ontogeny and succession of
      Lactobacillus plantarum subsp. plantarum and Lactobacillus plantarum subsp.
      argentoratensis.
AB  - Lactobacillus plantarum is one of the most extensively studied Lactobacillus
      species because of its presence in a variety of environmental niches,
      versatility, and metabolic capabilities, resulting in the use of this organism in
      many industrial applications. However, although extensive effort has been
      invested in screening this species from a variety of habitats, a reliable and
      accurate method for studying the succession and ontogeny of this organism in
      complex ecosystems is still required to confirm the activity of L. plantarum at
      the subspecies level. Therefore, in this study, novel subspecies-specific genes
      for the quantitative detection of two L. plantarum subspecies were identified by
      comparative genomic analysis. The specificity of primer sets for selected genes
      specific to each targeted microbe was confirmed in kimchi samples. Interestingly,
      in all the kimchi samples at 4  degrees C, the presence of L. plantarum subsp.
      argentoratensis was not observed. Hence, we found that low temperatures markedly
      affected the ontogeny of L. plantarum subsp. argentoratensis during kimchi
      fermentation. Subsequently, this touchstone method will offer new insight and
      metrics to understand the ontogeny and succession of L. plantarum subsp.
      plantarum and L. plantarum subsp. argentoratensis in various niches.

PMID- 29662106
TI  - Pharmacogenetics of platinum-based chemotherapy: impact of DNA repair and folate
      metabolism gene polymorphisms on prognosis of non-small cell lung cancer
      patients.
AB  - Chemotherapy based on platinum compounds is the standard treatment for NSCLC
      patients with EGFR wild type, and is also used as second line in mutated EGFR
      patients. Nevertheless, this therapy presents poor clinical outcomes. ERCC1,
      ERCC2, XRCC1, MDM2, MTHFR, MTR, and SLC19A1 gene polymorphisms may contribute to
      individual variation in response and survival to platinum-based chemotherapy. The
      aim of this study was to investigate the influence of these polymorphisms on
      response and survival of NSCLC patients treated with platinum-based chemotherapy.
      A retrospective-prospective cohorts study was conducted, including 141 NSCLC
      patients. Polymorphisms were analyzed by PCR real-time with Taqman(r) probes.
      Patients with ERCC1 rs3212986-GG (p = 0.0268; OR = 2.50; CI95% = 1.12-5.69) and
      XRCC1 rs25487-GG (p = 0.0161; OR = 2.99; CI95% = 1.26-7.62) genotype showed
      significantly better ORR. Cox survival analysis revealed that patients carrying
      the MDM2 rs1690924-GG genotype (p = 0.0345; HR = 1.99; CI95% = 1.05-3.80)
      presented higher risk of death. Furthermore, carriers of MTR rs1805087-A alleles
      (p = 0.0060; HR = 8.91; CI95% = 1.87-42.42) and SLC19A1 rs1051266-AA genotype (p
      = 0.0130; HR = 1.74; CI95% = 1.12-2.68) showed greater risk of progression. No
      influence of ERCC1 rs11615, ERCC2 rs13181, ERCC2 rs1799793, XRCC1 rs1799782, MDM2
      rs1470383, MTHFR rs1801131, and MTHFR rs1801133 on platinum-based chemotherapy
      clinical outcomes was found. In conclusion, our results suggest that ERCC1
      rs3212986, XRCC1 rs25487, MDM2 rs1690924, MTR rs1805087, and SLC19A1 rs1051266
      gene polymorphisms may significantly act as predictive factors in NSCLC patients
      treated with platinum-based chemotherapy.

PMID- 29662107
TI  - Scalability assessment of Group-IV mono-chalcogenide based tunnel FET.
AB  - Selection of appropriate channel material is the key to design high performance
      tunnel field effect transistor (TFET), which promises to outperform the
      conventional metal oxide semiconductor field effect transistor (MOSFET) in ultra
      low energy switching applications. Recently discovered atomically thin GeSe, a
      group IV mono-chalcogenide, can be a potential candidate owing to its direct
      electronic band gap and low carrier effective mass. In this work we employ
      ballistic quantum transport model to assess the intrinsic performance limit of
      monolayer GeSe-TFET. We first study the electronic band structure by regular and
      hybrid density functional theory and develop two band k . p hamiltonian for the
      material. We find that the complex band wraps itself within the conduction band
      and valence band edges and thus signifies efficient band to band tunneling
      mechanism. We then use the k . p hamiltonian to calculate self-consistent
      solution of the transport equations within the non-equilibrium Green's function
      formalism and the Poisson's equation based electrostatic potential. Keeping the
      OFF-current fixed at 10 pA/MUm we investigate different static and dynamic
      performance metrics (ON current, energy and delay) under three different constant
      field scaling rules: 40, 30 and 20 nm/V. Our study shows that monolayer GeSe-TFET
      is scalable till 8 nm while preserving ON/OFF current ratio higher than 104.

PMID- 29662109
TI  - Author Correction: Sensitivity enhancement of flexible gas sensors via conversion
      of inkjet-printed silver electrodes into porous gold counterparts.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 29662108
TI  - NIPS, a 3D network-integrated predictor of deleterious protein SAPs, and its
      application in cancer prognosis.
AB  - Identifying deleterious mutations remains a challenge in cancer genome sequencing
      projects, reflecting the vast number of candidate mutations per tumour and the
      existence of interpatient heterogeneity. Based on a 3D protein interaction
      network profiled via large-scale cross-linking mass spectrometry, we propose a
      weighted average formula involving the combination of three types of information
      into a 'meta-score'. We assume that a single amino acid polymorphism (SAP) may
      have a deleterious effect if the mutation rarely occurs naturally during
      evolution, if it inhibits binding between a pair of interacting proteins when
      located at their interface, or if it plays an important role in a protein
      interaction (PPI) network. Cross-validation indicated that this new method
      presents an AUC value of 0.93 and outperforms other widely used tools. The
      application of this method to the CPTAC colorectal cancer dataset enabled the
      accurate identification of validated deleterious mutations and yielded insights
      into their potential pathogenesis. Survival analysis showed that the accumulation
      of deleterious SAPs is significantly associated with a poor prognosis. The new
      method provides an alternative method to identifying and ranking deleterious
      cancer SAPs based on a 3D PPI network and will contribute to the understanding of
      pathogenesis and the discovery of prognostic biomarkers.

PMID- 29662110
TI  - Identification of human glycosyltransferase genes expressed in erythroid cells
      predicts potential carbohydrate blood group loci.
AB  - Glycans are biologically important structures synthesised by glycosyltransferase
      (GT) enzymes. Disruptive genetic null variants in GT genes can lead to serious
      illness but benign phenotypes are also seen, including antigenic differences on
      the red blood cell (RBC) surface, giving rise to blood groups. To characterise
      known and potential carbohydrate blood group antigens without a known underlying
      gene, we searched public databases for human GT loci and investigated their
      variation in the 1000 Genomes Project (1000 G). We found 244 GT genes,
      distributed over 44 families. All but four GT genes had missense variants or
      other variants predicted to alter the amino acid sequence, and 149 GT genes (61%)
      had variants expected to cause null alleles, often associated with antigen
      negative blood group phenotypes. In RNA-Seq data generated from erythroid cells,
      155 GT genes were expressed at a transcript level comparable to, or higher than,
      known carbohydrate blood group loci. Filtering for GT genes predicted to cause a
      benign phenotype, a set of 30 genes remained, 16 of which had variants in 1000 G
      expected to result in null alleles. Our results identify potential blood group
      loci and could serve as a basis for characterisation of the genetic background
      underlying carbohydrate RBC antigens.

PMID- 29662111
TI  - Author Correction: Structure-function relationships in ABCG2: insights from
      molecular dynamics simulations and molecular docking studies.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 29662113
TI  - Author Correction: Analyses of HIV-1 integrase sequences prior to South African
      national HIV-treatment program and availability of integrase inhibitors in Cape
      Town, South Africa.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 29662112
TI  - Optical Coherence Tomography Angiography Vessel Density Changes after Acute
      Intraocular Pressure Elevation.
AB  - To investigate changes in retinal vessel density in optic nerve head (ONH) and
      macula after acute intraocular pressure (IOP) elevation, we conducted a
      prospective observational study. Eyes with IOP rise >=5 mmHg after 2-hour dark
      room prone provocative test (DRPPT) were included. Vasculature of ONH and macula
      was examined by optical coherence tomography angiography (OCTA) at baseline and
      after DRPPT. Among the 65 eyes of 42 individuals, 40 eyes with qualified images
      were enrolled. Mean IOP rise was 9.6 +/- 4.2 mmHg (5.0-23.3 mmHg) after DRPPT.
      Retinal vessel density did not differ after IOP rise for either the papillary
      region (optic nerve head and radial peripapillary capillary layer) or the macula
      region (superficial, deep and outer retinal layer) (P > 0.05). Vessel density in
      each subregion did not change either. If only enrolled eyes with IOP rise >=10
      mmHg, similar results were obtained in condition of IOP increase by 15.0 +/- 3.6
      mmHg. To conclude, eyes with an acute IOP elevation by 10 or 15 mmHg for two
      hours, while the blood pressure remained constant, the vessel density in both ONH
      and macula region examined by OCTA did not show significant changes. The
      observations fit with an IOP-related autoregulation in retinal blood flow for a
      moderate elevation of IOP.

PMID- 29662114
TI  - Publisher Correction: Juvenile Hormone Epoxide Hydrolase: a Promising Target for
      Hemipteran Pest Management.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 29662115
TI  - Unusual sulfur isotope effect and extremely high critical temperature in H3S
      superconductor.
AB  - Recent experiments have set a new record for the transition temperature at which
      a material (hydrogen sulfide, H3S) becomes superconducting. Moreover, a
      pronounced isotope shift of T C in D3S is evidence of an existence of phonon
      mediated pairing mechanism of superconductivity that is consistent with the well
      established Bardeen-Cooper-Schrieffer scenario. Herein, we reported a theoretical
      studies of the influence of the substitution of 32S atoms by the heavier isotopes
      33S, 34S and 36S on the electronic properties, lattice dynamics and
      superconducting critical temperature of H3S. There are two equally fundamental
      results presented in this paper. The first one is an anomalous sulfur-derived
      superconducting isotope effect, which, if observed experimentally, will be
      subsequent argument that proves to the classical electron-phonon interaction. The
      second one is fact that critical temperature rise to extremely high value of 242
      K for H336S at 155 GPa. This result brings us closer to the room temperature
      superconductivity.

PMID- 29662116
TI  - Author Correction: Diffusive, Displacive Deformations and Local Phase
      Transformation Govern the Mechanics of Layered Crystals: The Case Study of
      Tobermorite.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 29662117
TI  - Treating vulvovaginal symptoms.

PMID- 29662118
TI  - Polyketides from two Chaetomium species and their biological functions.
AB  - Four new secondary metabolites, chaetosemins G-J (1-4), along with 11 known ones
      (5-15) were isolated from the culture of C. seminudum C208 and Chaetomium sp.
      C521. Their structures were determined by extensive NMR spectroscopic analyses.
      These metabolites were evaluated in vitro for antifungal, antioxidant, toxicity,
      and alpha-glucosidase inhibitory activities. Chaetosemin J (4) and monaschromone
      (5) significantly inhibited the growth of four plant pathogenic fungi Botrytis
      cinerea, Alternaria solani, Magnaporthe oryzae, and Gibberella saubinettii with
      the minimum inhibitory concentrations (MIC) values ranging from 6.25 to 25.0 MUM.
      Moreover, both epicoccone B (11) and flavipin (14) exhibited the DPPH free
      radical scavenging ability with IC50 values of 10.8 and 7.2 MUM, respectively,
      and had more potent alpha-glucosidase inhibition than the drug acarbose with IC50
      values of 27.3 and 33.8 MUM, respectively. Monaschromone (5) might act as the
      lead compound of pesticide.

PMID- 29662119
TI  - Impact of Diabetes Mellitus on the Risk of End-Stage Renal Disease in Patients
      with Systemic Lupus Erythematosus.
AB  - Systemic lupus erythematosus (SLE) patients are associated with insulin
      resistance and are at higher risk to develop diabetes mellitus (DM). SLE and DM
      could lead to renal failure respectively. However, it is unknown whether DM
      increases the risk of end-stage renal disease (ESRD) in SLE patients. This study
      aimed to evaluate potential synergistic effect of DM on SLE patients for
      development of ESRD. We conducted this study by using National Health Insurance
      Research Database of Taiwan. We recruited SLE patients with newly-diagnosed DM as
      the study cohort. A comparison cohort at a 1:1 ratio of SLE patients without DM
      matched by age, sex, age at the diagnosis of SLE, duration between diagnosis of
      SLE and DM, and various comorbidities through propensity score matching were
      recruited. After 5.01 +/- 3.13 years follow-up, the incidence of ESRD was
      significantly higher in the DM group than in the non-DM group (Incidence rate
      ratio: 2.71; 95% CI: 1.70-4.32). After control of confounding factors, DM was not
      an independent risk factor of ESRD. After starting dialysis, DM patients had a
      similar mortality rate to those without DM. In summary, SLE patients superimposed
      with subsequent DM are associated with potentially higher risk to develop ESRD.

PMID- 29662120
TI  - An early history of T cell-mediated cytotoxicity.
AB  - After 60 years of intense fundamental research into T cell-mediated cytotoxicity,
      we have gained a detailed knowledge of the cells involved, specific recognition
      mechanisms and post-recognition perforin-granzyme-based and FAS-based molecular
      mechanisms. What could not be anticipated at the outset was how discovery of the
      mechanisms regulating the activation and function of cytotoxic T cells would lead
      to new developments in cancer immunotherapy. Given the profound recent interest
      in therapeutic manipulation of cytotoxic T cell responses, it is an opportune
      time to look back on the early history of the field. This Timeline describes how
      the early findings occurred and eventually led to current therapeutic
      applications.

PMID- 29662121
TI  - Clocking in to immunity.
AB  - Circadian rhythms are a ubiquitous feature of virtually all living organisms,
      regulating a wide diversity of physiological systems. It has long been
      established that the circadian clockwork plays a key role in innate immune
      responses, and recent studies reveal that several aspects of adaptive immunity
      are also under circadian control. We discuss the latest insights into the genetic
      and biochemical mechanisms linking immunity to the core circadian clock of the
      cell and hypothesize as to why the immune system is so tightly controlled by
      circadian oscillations. Finally, we consider implications for human health,
      including vaccination strategies and the emerging field of chrono-immunotherapy.

PMID- 29662123
TI  - Nanowires under the microscope.

PMID- 29662122
TI  - Shallow deformation of the San Andreas fault 5 years following the 2004 Parkfield
      earthquake (Mw6) combining ERS2 and Envisat InSAR.
AB  - This study focuses on the shallow deformation that occurred during the 5 years
      following the Parkfield earthquake (28/09/2004, Mw 6, San Andreas Fault,
      California). We use Synthetic Aperture Radar interferometry (InSAR) to provide
      precise measurements of transient deformations after the Parkfield earthquake
      between 2005 and 2010. We propose a method to combine both ERS2 and ENVISAT
      interferograms to increase the temporal data sampling. Firstly, we combine 5
      years of available Synthetic Aperture Radar (SAR) acquisitions including both ERS
      2 and Envisat. Secondly, we stack selected interferograms (both from ERS2 and
      Envisat) for measuring the temporal evolution of the ground velocities at given
      time intervals. Thanks to its high spatial resolution, InSAR could provide new
      insights on the surface fault motion behavior over the 5 years following the
      Parkfield earthquake. As a complement to previous studies in this area, our
      results suggest that shallow transient deformations affected the Creeping
      Parkfield-Cholame sections of the San Andreas Fault after the 2004 Mw6 Parkfield
      earthquake.

PMID- 29662124
TI  - STAG2 deficiency induces interferon responses via cGAS-STING pathway and
      restricts virus infection.
AB  - Cohesin is a multi-subunit nuclear protein complex that coordinates sister
      chromatid separation during cell division. Highly frequent somatic mutations in
      genes encoding core cohesin subunits have been reported in multiple cancer types.
      Here, using a genome-wide CRISPR-Cas9 screening approach to identify host
      dependency factors and novel innate immune regulators of rotavirus (RV)
      infection, we demonstrate that the loss of STAG2, an important component of the
      cohesin complex, confers resistance to RV replication in cell culture and human
      intestinal enteroids. Mechanistically, STAG2 deficiency results in spontaneous
      genomic DNA damage and robust interferon (IFN) expression via the cGAS-STING
      cytosolic DNA-sensing pathway. The resultant activation of JAK-STAT signaling and
      IFN-stimulated gene (ISG) expression broadly protects against virus infections,
      including RVs. Our work highlights a previously undocumented role of the cohesin
      complex in regulating IFN homeostasis and identifies new therapeutic avenues for
      manipulating the innate immunity.

PMID- 29662125
TI  - Netrin-1 promotes diabetic corneal wound healing through molecular mechanisms
      mediated via the adenosine 2B receptor.
AB  - Netrins are secreted chemoattractants with the roles in axon guidance, cell
      migration and epithelial plasticity. In the present study, we investigated the
      roles of netrin-1 in the regulation of corneal epithelial wound healing,
      inflammation response and nerve fiber regeneration in diabetic mice and cultured
      corneal epithelial cells. In diabetic mice, the expression of netrin-1 was
      decreased when compared with that of normal mice. Furthermore, high glucose
      blocked the wounding-induced up-regulation of netrin-1 expression in corneal
      epithelial cells. Exogenous netrin-1 promoted the corneal epithelial wound
      healing in diabetic mice, and facilitated the proliferation and migration by
      reactivating the phosphorylation of ERK and EGFR in high-glucose treated corneal
      epithelial cells. Moreover, netrin-1 decreased the neutrophil infiltration and
      promoted M2 macrophage transition, accompanied with the attenuated expression of
      pro-inflammatory factors in diabetic mouse corneal epithelium. The promotions of
      netrin-1 on corneal epithelial wound healing and inflammation resolution were
      mediated at least through the adenosine 2B receptor. In addition, netrin-1
      promoted the regeneration of corneal nerve fibers that was impaired in diabetic
      mice. Taken together, netrin-1 regulates corneal epithelial wound healing,
      inflammation response and nerve fiber regeneration in diabetic mice, indicating
      the potential application for the therapy of diabetic keratopathy.

PMID- 29662126
TI  - Increased Abundance and Nursery Habitat Use of the Bull Shark (Carcharhinus
      leucas) in Response to a Changing Environment in a Warm-Temperate Estuary.
AB  - A general northward shift in marine species distributions has been observed in
      the western North Atlantic Ocean, which may have significant ecological
      consequences. Large coastal sharks can have wide migratory distributions but show
      fidelity to specific nursery habitats. Here we show evidence for nursery range
      expansion into Pamlico Sound, North Carolina by a marine apex predator, the Bull
      Shark (Carcharhinus leucas). Previous assessments have shown little to no use of
      estuarine North Carolina waters as nursery habitat by Bull Sharks from 1965-2011.
      Juvenile sharks were rarely captured in a fishery-independent gillnet survey
      conducted by the North Carolina Division of Marine Fisheries (NCDMF) from 2003
      2011, but were present every year from 2011-2016. Juvenile Bull Shark presence in
      the Sound was strongly related to early summer temperatures and late summer
      salinities, which have increased in the estuary over the 13 survey years, and
      further evidence for increasing water temperatures in Pamlico Sound was found in
      a 45-year data set for the NCDMF estuarine trawl survey. These results suggest
      that increasing water temperature and salinity have allowed Bull Sharks to expand
      their nursery habitat. This shift will have unknown, but potentially strong,
      impacts on both the local ecosystem and interactions with humans.

PMID- 29662127
TI  - Human mandibular shape is associated with masticatory muscle force.
AB  - Understanding how and to what extent forces applied to the mandible by the
      masticatory muscles influence its form, is of considerable importance from
      clinical, anthropological and evolutionary perspectives. This study investigates
      these questions. Head CT scans of 382 adults were utilized to measure masseter
      and temporalis muscle cross-sectional areas (CSA) as a surrogate for muscle
      force, and 17 mandibular anthropometric measurements. Sixty-two mandibles of
      young individuals (20-40 years) whose scans were without artefacts (e.g., due to
      tooth filling) were segmented and landmarked for geometric morphometric analysis.
      The association between shape and muscle CSA (controlled for size) was assessed
      using two-block partial least squares analysis. Correlations were computed
      between mandibular variables and muscle CSAs (all controlled for size). A
      significant association was found between mandibular shape and muscle CSAs, i.e.
      larger CSAs are associated with a wider more trapezoidal ramus, more massive
      coronoid, more rectangular body and a more curved basal arch. Linear measurements
      yielded low correlations with muscle CSAs. In conclusion, this study demonstrates
      an association between mandibular muscle force and mandibular shape, which is not
      as readily identified from linear measurements. Retrodiction of masticatory
      muscle force and so of mandibular loading is therefore best based on overall
      mandibular shape.

PMID- 29662128
TI  - The extracellular domain of Staphylococcus aureus LtaS binds insulin and induces
      insulin resistance during infection.
AB  - Insulin resistance is a risk factor for obesity and diabetes and predisposes
      individuals to Staphylococcus aureus colonization; however, the contribution of
      S. aureus to insulin resistance remains unclear. Here, we show that S. aureus
      infection causes impaired glucose tolerance via secretion of an insulin-binding
      protein extracellular domain of LtaS, eLtaS, which blocks insulin-mediated
      glucose uptake. Notably, eLtaS transgenic mice (eLtaS trans ) exhibited a
      metabolic syndrome similar to that observed in patients, including increased food
      and water consumption, impaired glucose tolerance and decreased hepatic glycogen
      synthesis. Furthermore, transgenic mice showed significant metabolic differences
      compared to their wild-type counterparts, particularly for the early insulin
      resistance marker alpha-hydroxybutyrate. We subsequently developed a full human
      monoclonal antibody against eLtaS that blocked the interaction between eLtaS and
      insulin, which effectively restored glucose tolerance in eLtaS trans and S.
      aureus-challenged mice. Thus, our results reveal a mechanism for S. aureus
      induced insulin resistance.

PMID- 29662131
TI  - First-Principle Study of the Optical Properties of Dilute-P GaN1-xPx Alloys.
AB  - An investigation on the optical properties of dilute-P GaN1-xPx alloys by First
      Principle Density Functional Theory (DFT) methods is presented, for phosphorus
      (P) content varying from 0% up to 12.5%. Findings on the imaginary and real part
      of the dielectric function are analyzed and the results are compared with
      previously reported theoretical works on GaN. The complex refractive index,
      normal-incidence reflectivity and birefringence are presented and a difference in
      the refractive index in the visible regime between GaN and GaNP alloys of ~0.3
      can be engineered by adding minute amounts of phosphorus, indicating strong
      potential for refractive index tunability. The optical properties of the GaN1-xPx
      alloys indicate their strong potential for implementation in various III-nitride
      based photonic waveguide applications and Distributed Bragg Reflectors (DBR).

PMID- 29662130
TI  - Application of improved approach to evaluate a community intervention to reduce
      exposure of young children living in farmworker households to organophosphate
      pesticides.
AB  - The take-home pathway is a significant source of organophosphate pesticide
      exposure for young children (3-5 years old) living with an adult farmworker. This
      avoidable exposure pathway is an important target for intervention. We selected
      24 agricultural communities in the Yakima Valley of Washington State and randomly
      assigned them to receive an educational intervention (n = 12) to reduce
      children's pesticide exposure or usual care (n = 12). We assessed exposure to
      pesticides in nearly 200 adults and children during the pre and post-intervention
      periods by measuring metabolites in urine. We compared pre- and post-intervention
      exposures by expressing the child's pesticide metabolite concentration as a
      fraction of the adult's concentration living in the same household, because the
      amount of pesticides applied during the collection periods varied. Exposures in
      our community were consistently higher, sometimes above the 95th percentile of
      the exposures reported by the National Health and Nutrition Examination Survey
      (NHANES). While intervention and control communities demonstrated a reduction in
      the ratio of child to adult exposure, this reduction was more pronounced in
      intervention communities (2.7-fold, p < 0.001 compared to 1.7-fold, p = 0.052 for
      intervention and control, respectively). By examining the child/adult biomarker
      ratio, we demonstrated that our community-based intervention was effective in
      reducing pesticide exposure to children in agricultural communities.

PMID- 29662129
TI  - Intracellular replication of Streptococcus pneumoniae inside splenic macrophages
      serves as a reservoir for septicaemia.
AB  - Bacterial septicaemia is a major cause of mortality, but its pathogenesis remains
      poorly understood. In experimental pneumococcal murine intravenous infection, an
      initial reduction of bacteria in the blood is followed hours later by a fatal
      septicaemia. These events represent a population bottleneck driven by efficient
      clearance of pneumococci by splenic macrophages and neutrophils, but as we show
      in this study, accompanied by occasional intracellular replication of bacteria
      that are taken up by a subset of CD169+ splenic macrophages. In this model,
      proliferation of these sequestered bacteria provides a reservoir for
      dissemination of pneumococci into the bloodstream, as demonstrated by its
      prevention using an anti-CD169 monoclonal antibody treatment. Intracellular
      replication of pneumococci within CD169+ splenic macrophages was also observed in
      an ex vivo porcine spleen, where the microanatomy is comparable with humans. We
      also showed that macrolides, which effectively penetrate macrophages, prevented
      septicaemia, whereas beta-lactams, with inefficient intracellular penetration,
      failed to prevent dissemination to the blood. Our findings define a shift in our
      understanding of the pneumococcus from an exclusively extracellular pathogen to
      one with an intracellular phase. These findings open the door to the development
      of treatments that target this early, previously unrecognized intracellular phase
      of bacterial sepsis.

PMID- 29662132
TI  - Immune memory in the brain.

PMID- 29662133
TI  - When sex differences lead to extinction.

PMID- 29662134
TI  - Bounteous black holes at the Galactic Centre.

PMID- 29662135
TI  - A stockpile of antiviral defences.

PMID- 29662138
TI  - Regulate artificial intelligence to avert cyber arms race.

PMID- 29662140
TI  - Association between heart failure with preserved ejection fraction and
      hypertensive retinopathy: more questions than answers!

PMID- 29662139
TI  - Decreased expression of JHDMID in placenta is associated with preeclampsia
      through HLA-G.
AB  - The exact mechanism of preeclampsia (PE) remains unclear, accumulating researches
      have indicated multiple epigenetic factors relate to PE and histone methylation
      plays a crucial role in modifying the gene expression. So we aimed to confirm
      that abnormal expression of histone demethylase JHDM1D contributes to PE and
      lower expression of HLA-G in PE. We tested the expression of JHDM1D, H3K9me2, and
      H3K27me2 in the placentas of PE and normal control (NC)women who had a healthy
      pregnancy with Immunohistochemistry and we found that JHDM1D, H3K9me2, and
      H3K27me2 were all mainly expressed in the nuclei of the extra-villous
      trophoblasts (EVTs). JHDM1D was lower expressed in PE than in NC placentas,
      corresponding with the mRNA level and protein level with qTR-PCR and western
      blot, while H3K9me2 and H3K27me2 were higher expressed in PE. We further
      investigated the biological functions of JHDM1D in HTR-8/SVneo cells. We found
      that siJHDM1D inhibited cell growth after 24 h of the transfection and reduced
      the invasion, while increasing the apoptosis of HTR-8/SVneo. We then constructed
      the siJHDM1D stable cell line and confirmed with CHIP-qPCR that siJHDM1D
      inhibited the expression of HLA-G through increased the enrichment of H3K9me2 and
      H3K27me2 in the JHDM1D bounding region of HLA-G. Taken together, our study
      confirms that decreased expression of JHDM1D is associated with PE through down
      regulating HLA-G and casts new light to the diagnosis and therapy of PE.

PMID- 29662141
TI  - The cytoplasmic dynein transport machinery and its many cargoes.
AB  - Cytoplasmic dynein 1 is an important microtubule-based motor in many eukaryotic
      cells. Dynein has critical roles both in interphase and during cell division.
      Here, we focus on interphase cargoes of dynein, which include membrane-bound
      organelles, RNAs, protein complexes and viruses. A central challenge in the field
      is to understand how a single motor can transport such a diverse array of cargoes
      and how this process is regulated. The molecular basis by which each cargo is
      linked to dynein and its cofactor dynactin has started to emerge. Of particular
      importance for this process is a set of coiled-coil proteins - activating
      adaptors - that both recruit dynein-dynactin to their cargoes and activate dynein
      motility.

PMID- 29662142
TI  - The Hepatitis Delta Virus accumulation requires paraspeckle components and
      affects NEAT1 level and PSP1 localization.
AB  - The Hepatitis Delta Virus (HDV) relies mainly on host proteins for its
      replication. We previously identified that PSF and p54nrb associate with the HDV
      RNA genome during viral replication. Together with PSP1, these proteins are part
      of paraspeckles, which are subnuclear bodies nucleated by the long non-coding RNA
      NEAT1. In this work, we established the requirement for PSF, p54nrb and PSP1 in
      HDV replication using RNAi-mediated knockdown in HEK-293 cells replicating the
      HDV RNA genome. We determined that HDV replication induces the delocalization of
      PSP1 to cytoplasmic foci containing PABP and increases NEAT1 level causing an
      enlargement of NEAT1 foci. Overall, our data support a role for the main
      paraspeckles proteins in HDV life cycle and indicate that HDV replication causes
      a cellular stress and induces both a delocalization of the PSP1 to the cytoplasm
      and a disruption of paraspeckles.

PMID- 29662143
TI  - Observation of Wavelength Tuning and Bound States in Fiber Lasers.
AB  - We report an experimental observation of wavelength tuning and bound states in
      fiber lasers. A Mach-Zehnder interferometer (MZI) is adopted as an intra-cavity
      tunable filter to realize large-scale wavelength tuning and bandwidth
      controlling. By finely manipulating the MZI and intra-cavity polarization state,
      continuous wavelength-tunable operation from 1550.7 nm to 1580.8 nm is achieved.
      Meanwhile, the spectral bandwidth varying from 1.85 nm to 3.41 nm is also
      controlled by broadening the free spectrum range (FSR) of the MZI. Additionally,
      with modest polarization adjustment, both tightly and loosely bound states are
      experimentally observed, which can be validated by the numerical simulations. The
      results indicate that the proposed fiber laser is attractive for
      telecommunication systems, on account that the tuning feature can be applied to
      wavelength-division multiplexer (WDM) and the various soliton bound states could
      contribute to the high-level modulation format.

PMID- 29662144
TI  - Selection of stable reference genes for RT-qPCR in Rhodococcus opacus PD630.
AB  - Rhodococcus opacus PD630 is a gram-positive bacterium with promising attributes
      for the conversion of lignin into valuable fuels and chemicals. To develop an
      organism as a cellular factory, it is necessary to have a deep understanding of
      its metabolism and any heterologous pathways being expressed. For the purpose of
      quantifying gene transcription, reverse transcription quantitative PCR (RT-qPCR)
      is the gold standard due to its sensitivity and reproducibility. However, RT-qPCR
      requires the use of reference genes whose expression is stable across distinct
      growth or treatment conditions to normalize the results. Unfortunately, no in
      depth analysis of stable reference genes has been conducted in Rhodococcus,
      inhibiting the utilization of RT-qPCR in R. opacus. In this work, ten candidate
      reference genes, chosen based on previously collected RNA sequencing data or
      literature, were examined under four distinct growth conditions using three
      mathematical programs (BestKeeper, Normfinder, and geNorm). Based on this
      analysis, the minimum number of reference genes required was found to be two, and
      two separate pairs of references genes were identified as optimal normalization
      factors for when ribosomal RNA is either present or depleted. This work
      represents the first validation of reference genes for Rhodococcus, providing a
      valuable starting point for future research.

PMID- 29662145
TI  - The ecology and diversity of microbial eukaryotes in geothermal springs.
AB  - Decades of research into the Bacteria and Archaea living in geothermal spring
      ecosystems have yielded great insight into the diversity of life and organismal
      adaptations to extreme environmental conditions. Surprisingly, while microbial
      eukaryotes (protists) are also ubiquitous in many environments, their diversity
      across geothermal springs has mostly been ignored. We used high-throughput
      sequencing to illuminate the diversity and structure of microbial eukaryotic
      communities found in 160 geothermal springs with broad ranges in temperature and
      pH across the Taupo Volcanic Zone in New Zealand. Protistan communities were
      moderately predictable in composition and varied most strongly across gradients
      in pH and temperature. Moreover, this variation mirrored patterns observed for
      bacterial and archaeal communities across the same spring samples, highlighting
      that there are similar ecological constraints across the tree of life. While
      extreme pH values were associated with declining protist diversity, high
      temperature springs harbored substantial amounts of protist diversity. Although
      protists are often overlooked in geothermal springs and other extreme
      environments, our results indicate that such environments can host distinct and
      diverse protistan communities.

PMID- 29662146
TI  - Why do microbes exhibit weak biogeographic patterns?
AB  - Analysis of patterns in the distribution of taxa can provide important insights
      into ecological and evolutionary processes. Microbial biogeographic patterns
      almost always appear to be weaker than those reported for plant and animal taxa.
      It is as yet unclear why this is the case. Some argue that microbial diversity
      scales differently over space because microbial taxa are fundamentally different
      in their abundance, longevity and dispersal abilities. Others have argued that
      differences in scaling are an artifact of how we assess microbial biogeography,
      driven, for example, by differences in taxonomic resolution, spatial scale,
      sampling effort or community activity/dormancy. We tested these alternative
      explanations by comparing bacterial biogeographic patterns in soil to those of
      trees found in a forest in Gabon. Altering taxonomic resolution, excluding
      inactive individuals, or adjusting for differences in spatial scale were
      insufficient to change the rate of microbial taxonomic turnover. In contrast, we
      account for the differences in spatial turnover between these groups by
      equalizing sampling extent. Our results suggest that spatial scaling differences
      between microbial and plant diversity are likely not due to fundamental
      differences in biology, and that sampling extent should be taken into account
      when comparing the biogeographic patterns of microorganisms and larger organisms.

PMID- 29662147
TI  - A methanotrophic archaeon couples anaerobic oxidation of methane to Fe(III)
      reduction.
AB  - Microbially mediated anaerobic oxidation of methane (AOM) is a key process in the
      regulation of methane emissions to the atmosphere. Iron can serve as an electron
      acceptor for AOM, and it has been suggested that Fe(III)-dependent AOM
      potentially comprises a major global methane sink. Although it has been proposed
      that anaerobic methanotrophic (ANME) archaea can facilitate this process, their
      active metabolic pathways have not been confirmed. Here we report the enrichment
      and characterisation of a novel archaeon in a laboratory-scale bioreactor fed
      with Fe(III) oxide (ferrihydrite) and methane. Long-term performance data, in
      conjunction with the 13C- and 57Fe-labelling batch experiments, demonstrated that
      AOM was coupled to Fe(III) reduction to Fe(II) in this bioreactor. Metagenomic
      analysis showed that this archaeon belongs to a novel genus within family
      Candidatus Methanoperedenaceae, and possesses genes encoding the "reverse
      methanogenesis" pathway, as well as multi-heme c-type cytochromes which are
      hypothesised to facilitate dissimilatory Fe(III) reduction. Metatranscriptomic
      analysis revealed upregulation of these genes, supporting that this archaeon can
      independently mediate AOM using Fe(III) as the terminal electron acceptor. We
      propose the name Candidatus "Methanoperedens ferrireducens" for this
      microorganism. The potential role of "M. ferrireducens" in linking the carbon and
      iron cycles in environments rich in methane and iron should be investigated in
      future research.

PMID- 29662148
TI  - Emergence of Human G2P[4] Rotaviruses in the Post-vaccination Era in South Korea:
      Footprints of Multiple Interspecies Re-assortment Events.
AB  - After the introduction of two global rotavirus vaccines, RotaTeq in 2007 and
      Rotarix in 2008 in South Korea, G1[P8] rotavirus was the major rotavirus genotype
      in the country until 2012. However, in this study, an emergence of G2P[4] as the
      dominant genotype during the 2013 to 2015 season has been reported. Genetic
      analysis revealed that these viruses had typical DS-1-like genotype constellation
      and showed evidence of re-assortment in one or more genome segments, including
      the incorporation of NSP4 genes from strains B-47/2008 from a cow and
      R4/Haryana/2007 from a buffalo in India, and the VP1 and VP3 genes from strain
      GO34/1999 from a goat in Bangladesh. Compared to the G2 RotaTeq vaccine strain,
      17-24 amino acid changes, specifically A87T, D96N, S213D, and S242N substitutions
      in G2 epitopes, were observed. These results suggest that multiple interspecies
      re-assortment events might have contributed to the emergence of G2P[4]
      rotaviruses in the post-vaccination era in South Korea.

PMID- 29662149
TI  - Author Correction: WNT-activated bone grafts repair osteonecrotic lesions in aged
      animals.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 29662151
TI  - New subtypes of high-grade neuroendocrine tumours revealed.

PMID- 29662150
TI  - Postoperative chemoradiotherapy versus radiotherapy for high-risk cutaneous
      disease.

PMID- 29662152
TI  - Targeted combination has synergy in MCL.

PMID- 29662153
TI  - Author Correction: Alpha-oxoglutarate inhibits the proliferation of immortalized
      normal bladder epithelial cells via an epigenetic switch involving ARID1A.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 29662154
TI  - Parent-of-origin effect of hypomorphic pathogenic variants and somatic mosaicism
      impact on phenotypic expression of retinoblastoma.
AB  - Retinoblastoma is the most common eye cancer in children. Numerous families have
      been described displaying reduced penetrance and expressivity. An extensive
      molecular characterization of seven families led us to characterize the two main
      mechanisms impacting on phenotypic expression, as follows: (i) mosaicism of
      amorphic pathogenic variants; and (ii) parent-of-origin-effect of hypomorphic
      pathogenic variants. Somatic mosaicism for RB1 splicing variants (c.1960+5G>C and
      c.2106+2T>C), leading to a complete loss of function was demonstrated by high
      depth NGS in two families. In both cases, the healthy carrier parent (one with
      retinoma) showed a variant frequency lower than that expected for a heterozygous
      individual, indicating a 56-60% mosaicism level. Previous evidences of a ~3-fold
      excess of RB1 maternal canonical transcript led us to hypothesize that this
      differential allelic expression could influence phenotypic outcome in families at
      risk for RB onset. Accordingly, in five families, we identified a higher tumor
      risk associated with paternally inherited hypomorphic pathogenic variants, namely
      a deletion resulting in the loss of 37 amino acids at the N-terminus (c.608
      16_608del), an exonic substitution with a "leaky" splicing effect (c.1331A>G), a
      partially deleterious substitution (c.1981C>T) and a truncating C-terminal
      variant (c.2663+2T>C). The identification of these mechanisms changes the
      genetic/prenatal counseling and the clinical management of families, indicating a
      higher recurrence risk when the hypomorphic pathogenic variant is inherited from
      the father, and suggesting the need for second tumor surveillance in unaffected
      carriers at risk of developing adult-onset cancer such as osteosarcoma or
      leiomyosarcoma.

PMID- 29662155
TI  - IRay therapy as an adjuvant therapy in newly diagnosed patients with neovascular
      age-related macular degeneration.
AB  - OBJECTIVES: To determine the safety and efficacy at 12 months of follow-up after
      stereotactic radiotherapy in combination therapy with intravitreal ranibizumab
      injections in treatment naive patients with neovascular age-related macular
      degeneration. METHODS: Retrospective data analysis in patients who received
      stereotactic radiotherapy (IRay Therapy) during the induction phase of
      intravitreal ranibizumab injections and a monotherapy control group. RESULTS: The
      baseline VA in the IRay and control group was 59.87 and 59.12 letters
      respectively. The real world visual acuity outcomes for the IRay group showed a
      mean gain of +3.0 letters at 12 months. The historical control group had a mean
      change of - 0.3 letters. The average number of injections for the IRay group and
      control group over 12 months was 4.45 and 5.64, respectively with three loading
      injections. Excluding the loading phase, the difference over 12 months was a
      45.2% reduction in injections (P < 0.001). The number of subjects in the IRay
      group that didn't require further injections following the loading phase was 45.5
      vs. 24.0% control group (P = 0.005). The difference in mean change in central
      macular thickness from baseline is significant at 6 (P = 0.010) and 12 months (P
      < 0.01). There were no safety concerns with the IRay therapy group. CONCLUSIONS:
      Stereotactic radiotherapy in the induction phase of intravitreal injections of
      ranibizumab for treatment naive patients with neovascular age-related macular
      degeneration, resulted in improved visual outcome, statistically fewer injections
      and statistically drier macular at 12 months, compared to historical controls
      treated with monotherapy intravitreal ranibizumab injections.

PMID- 29662156
TI  - Enhanced spin pumping into superconductors provides evidence for superconducting
      pure spin currents.
AB  - Unlike conventional spin-singlet Cooper pairs, spin-triplet pairs can carry
      spin1,2. Triplet supercurrents were discovered in Josephson junctions with
      metallic ferromagnet spacers, where spin transport can occur only within the
      ferromagnet and in conjunction with a charge current. Ferromagnetic resonance
      injects a pure spin current from a precessing ferromagnet into adjacent non
      magnetic materials3,4. For spin-singlet pairing, the ferromagnetic resonance spin
      pumping efficiency decreases below the critical temperature (Tc) of a coupled
      superconductor5,6. Here we present ferromagnetic resonance experiments in which
      spin sink layers with strong spin-orbit coupling are added to the superconductor.
      Our results show that the induced spin currents, rather than being suppressed,
      are substantially larger in the superconducting state compared with the normal
      state; although further work is required to establish the details of the spin
      transport process, we show that this cannot be mediated by quasiparticles and is
      most likely a triplet pure spin supercurrent.

PMID- 29662157
TI  - Pyroelectric energy conversion with large energy and power density in relaxor
      ferroelectric thin films.
AB  - The need for efficient energy utilization is driving research into ways to
      harvest ubiquitous waste heat. Here, we explore pyroelectric energy conversion
      from low-grade thermal sources that exploits strong field- and temperature
      induced polarization susceptibilities in the relaxor ferroelectric
      0.68Pb(Mg1/3Nb2/3)O3-0.32PbTiO3. Electric-field-driven enhancement of the
      pyroelectric response (as large as -550 MUC m-2 K-1) and suppression of the
      dielectric response (by 72%) yield substantial figures of merit for pyroelectric
      energy conversion. Field- and temperature-dependent pyroelectric measurements
      highlight the role of polarization rotation and field-induced polarization in
      mediating these effects. Solid-state, thin-film devices that convert low-grade
      heat into electrical energy are demonstrated using pyroelectric Ericsson cycles,
      and optimized to yield maximum energy density, power density and efficiency of
      1.06 J cm-3, 526 W cm-3 and 19% of Carnot, respectively; the highest values
      reported to date and equivalent to the performance of a thermoelectric with an
      effective ZT ~ 1.16 for a temperature change of 10 K. Our findings suggest that
      pyroelectric devices may be competitive with thermoelectric devices for low-grade
      thermal harvesting.

PMID- 29662158
TI  - More power to pyroelectrics.

PMID- 29662159
TI  - Hole trap formation in polymer light-emitting diodes under current stress.
AB  - Polymer light-emitting diodes (PLEDs) are attractive for use in large-area
      displays and lighting panels, but their limited stability under current stress
      impedes commercialization. In spite of large efforts over the last two decades a
      fundamental understanding of the degradation mechanisms has not been
      accomplished. Here we demonstrate that the voltage drift of a PLED driven at
      constant current is caused by the formation of hole traps, which leads to
      additional non-radiative recombination between free electrons and trapped holes.
      The observed trap formation rate is consistent with exciton-free hole
      interactions as the main mechanism behind PLED degradation, enabling us to unify
      the degradation behaviour of various poly(p-phenylene) derivatives. The knowledge
      that hole trap formation is the cause of PLED degradation means that we can
      suppress the negative effect of hole traps on voltage and efficiency by blending
      the light-emitting polymer with a large-bandgap semiconductor. Owing to trap
      dilution these blended PLEDs show unprecedented stability.

PMID- 29662160
TI  - Highly reversible zinc metal anode for aqueous batteries.
AB  - Metallic zinc (Zn) has been regarded as an ideal anode material for aqueous
      batteries because of its high theoretical capacity (820 mA h g-1), low potential
      (-0.762 V versus the standard hydrogen electrode), high abundance, low toxicity
      and intrinsic safety. However, aqueous Zn chemistry persistently suffers from
      irreversibility issues, as exemplified by its low coulombic efficiency (CE) and
      dendrite growth during plating/ stripping, and sustained water consumption. In
      this work, we demonstrate that an aqueous electrolyte based on Zn and lithium
      salts at high concentrations is a very effective way to address these issues.
      This unique electrolyte not only enables dendrite-free Zn plating/stripping at
      nearly 100% CE, but also retains water in the open atmosphere, which makes
      hermetic cell configurations optional. These merits bring unprecedented
      flexibility and reversibility to Zn batteries using either LiMn2O4 or O2 cathodes
      the former deliver 180 W h kg-1 while retaining 80% capacity for >4,000 cycles,
      and the latter deliver 300 W h kg-1 (1,000 W h kg-1 based on the cathode) for
      >200 cycles.

PMID- 29662161
TI  - Pan-cancer analysis of somatic mutations and transcriptomes reveals common
      functional gene clusters shared by multiple cancer types.
AB  - To discover functional gene clusters across cancers, we performed a systematic
      pan-cancer analysis of 33 cancer types. We identified genes that were associated
      with somatic mutations and were the cores of a co-expression network. We found
      that multiple cancer types have relatively exclusive hub genes individually;
      however, the hub genes cooperate with each other based on their functional
      relationship. When we built a protein-protein interaction network of hub genes
      and found nine functional gene clusters across cancer types, the gene clusters
      divided not only the region of the network map, but also the function of the
      network by their distinct roles related to the development and progression of
      cancer. This functional relationship between the clusters and cancers was
      underpinned by the high expression of module genes and enrichment of programmed
      cell death, and known candidate cancer genes. In addition to protein-coding hub
      genes, non-coding hub genes had a possible relationship with cancer. Overall, our
      approach of investigating cancer genes enabled finding pan-cancer hub genes and
      common functional gene clusters shared by multiple cancer types based on the
      expression status of the primary tumour and the functional relationship of genes
      in the biological network.

PMID- 29662162
TI  - A switch point in the molecular chaperone Hsp90 responding to client interaction.
AB  - Heat shock protein 90 (Hsp90) is a dimeric molecular chaperone that undergoes
      large conformational changes during its functional cycle. It has been established
      that conformational switch points exist in the N-terminal (Hsp90-N) and C
      terminal (Hsp90-C) domains of Hsp90, however information for switch points in the
      large middle-domain (Hsp90-M) is scarce. Here we report on a tryptophan residue
      in Hsp90-M as a new type of switch point. Our study shows that this conserved
      tryptophan senses the interaction of Hsp90 with a stringent client protein and
      transfers this information via a cation-pi interaction with a neighboring lysine.
      Mutations at this position hamper the communication between domains and the
      ability of a client protein to affect the Hsp90 cycle. The residue thus allows
      Hsp90 to transmit information on the binding of a client from Hsp90-M to Hsp90-N
      which is important for progression of the conformational cycle and the efficient
      processing of client proteins.

PMID- 29662163
TI  - Polymer physics predicts the effects of structural variants on chromatin
      architecture.
AB  - Structural variants (SVs) can result in changes in gene expression due to
      abnormal chromatin folding and cause disease. However, the prediction of such
      effects remains a challenge. Here we present a polymer-physics-based approach
      (PRISMR) to model 3D chromatin folding and to predict enhancer-promoter contacts.
      PRISMR predicts higher-order chromatin structure from genome-wide chromosome
      conformation capture (Hi-C) data. Using the EPHA4 locus as a model, the effects
      of pathogenic SVs are predicted in silico and compared to Hi-C data generated
      from mouse limb buds and patient-derived fibroblasts. PRISMR deconvolves the
      folding complexity of the EPHA4 locus and identifies SV-induced ectopic contacts
      and alterations of 3D genome organization in homozygous or heterozygous states.
      We show that SVs can reconfigure topologically associating domains, thereby
      producing extensive rewiring of regulatory interactions and causing disease by
      gene misexpression. PRISMR can be used to predict interactions in silico, thereby
      providing a tool for analyzing the disease-causing potential of SVs.

PMID- 29662165
TI  - Deconvolution of seed and RNA-binding protein crosstalk in RNAi-based functional
      genomics.
AB  - RNA interference (RNAi) is a major, powerful platform for gene perturbations, but
      is restricted by off-target mechanisms. Communication between RNAs, small RNAs,
      and RNA-binding proteins (RBPs) is a pervasive feature of cellular RNA networks.
      We present a crosstalk scenario, designated as crosstalk with endogenous RBPs'
      (ceRBP), in which small interfering RNAs or microRNAs with seed sequences that
      overlap RBP motifs have extended biological effects by perturbing endogenous RBP
      activity. Systematic analysis of small interfering RNA (siRNA) off-target data
      and genome-wide RNAi cancer lethality screens using 501 human cancer cell lines,
      a cancer dependency map, identified that seed-to-RBP crosstalk is widespread,
      contributes to off-target activity, and affects RNAi performance. Specifically,
      deconvolution of the interactions between gene knockdown and seed-mediated
      silencing effects in the cancer dependency map showed widespread contributions of
      seed-to-RBP crosstalk to growth-phenotype modulation. These findings suggest a
      novel aspect of microRNA biology and offer a basis for improvement of RNAi agents
      and RNAi-based functional genomics.

PMID- 29662164
TI  - Transcription factors operate across disease loci, with EBNA2 implicated in
      autoimmunity.
AB  - Explaining the genetics of many diseases is challenging because most associations
      localize to incompletely characterized regulatory regions. Using new
      computational methods, we show that transcription factors (TFs) occupy multiple
      loci associated with individual complex genetic disorders. Application to 213
      phenotypes and 1,544 TF binding datasets identified 2,264 relationships between
      hundreds of TFs and 94 phenotypes, including androgen receptor in prostate cancer
      and GATA3 in breast cancer. Strikingly, nearly half of systemic lupus
      erythematosus risk loci are occupied by the Epstein-Barr virus EBNA2 protein and
      many coclustering human TFs, showing gene-environment interaction. Similar EBNA2
      anchored associations exist in multiple sclerosis, rheumatoid arthritis,
      inflammatory bowel disease, type 1 diabetes, juvenile idiopathic arthritis and
      celiac disease. Instances of allele-dependent DNA binding and downstream effects
      on gene expression at plausibly causal variants support genetic mechanisms
      dependent on EBNA2. Our results nominate mechanisms that operate across risk loci
      within disease phenotypes, suggesting new models for disease origins.

PMID- 29662166
TI  - Signatures of negative selection in the genetic architecture of human complex
      traits.
AB  - We develop a Bayesian mixed linear model that simultaneously estimates single
      nucleotide polymorphism (SNP)-based heritability, polygenicity (proportion of
      SNPs with nonzero effects), and the relationship between SNP effect size and
      minor allele frequency for complex traits in conventionally unrelated individuals
      using genome-wide SNP data. We apply the method to 28 complex traits in the UK
      Biobank data (N = 126,752) and show that on average, 6% of SNPs have nonzero
      effects, which in total explain 22% of phenotypic variance. We detect significant
      (P < 0.05/28) signatures of natural selection in the genetic architecture of 23
      traits, including reproductive, cardiovascular, and anthropometric traits, as
      well as educational attainment. The significant estimates of the relationship
      between effect size and minor allele frequency in complex traits are consistent
      with a model of negative (or purifying) selection, as confirmed by forward
      simulation. We conclude that negative selection acts pervasively on the genetic
      variants associated with human complex traits.

PMID- 29662169
TI  - Distinct myeloid cell subsets promote meningeal remodeling and vascular repair
      after mild traumatic brain injury.
AB  - Mild traumatic brain injury (mTBI) can cause meningeal vascular injury and cell
      death that spreads into the brain parenchyma and triggers local inflammation and
      recruitment of peripheral immune cells. The factors that dictate meningeal
      recovery after mTBI are unknown at present. Here we demonstrated that most
      patients who had experienced mTBI resolved meningeal vascular damage within 2-3
      weeks, although injury persisted for months in a subset of patients. To
      understand the recovery process, we studied a mouse model of mTBI and found
      extensive meningeal remodeling that was temporally reliant on infiltrating
      myeloid cells with divergent functions. Inflammatory myelomonocytic cells
      scavenged dead cells in the lesion core, whereas wound-healing macrophages
      proliferated along the lesion perimeter and promoted angiogenesis through the
      clearance of fibrin and production of the matrix metalloproteinase MMP-2.
      Notably, a secondary injury experienced during the acute inflammatory phase
      aborted this repair program and enhanced inflammation, but a secondary injury
      experienced during the wound-healing phase did not. Our findings demonstrate that
      meningeal vasculature can undergo regeneration after mTBI that is dependent on
      distinct myeloid cell subsets.

PMID- 29662167
TI  - Sequencing of prostate cancers identifies new cancer genes, routes of progression
      and drug targets.
AB  - Prostate cancer represents a substantial clinical challenge because it is
      difficult to predict outcome and advanced disease is often fatal. We sequenced
      the whole genomes of 112 primary and metastatic prostate cancer samples. From
      joint analysis of these cancers with those from previous studies (930 cancers in
      total), we found evidence for 22 previously unidentified putative driver genes
      harboring coding mutations, as well as evidence for NEAT1 and FOXA1 acting as
      drivers through noncoding mutations. Through the temporal dissection of
      aberrations, we identified driver mutations specifically associated with steps in
      the progression of prostate cancer, establishing, for example, loss of CHD1 and
      BRCA2 as early events in cancer development of ETS fusion-negative cancers.
      Computational chemogenomic (canSAR) analysis of prostate cancer mutations
      identified 11 targets of approved drugs, 7 targets of investigational drugs, and
      62 targets of compounds that may be active and should be considered candidates
      for future clinical trials.

PMID- 29662168
TI  - Genome-wide association meta-analysis of individuals of European ancestry
      identifies new loci explaining a substantial fraction of hair color variation and
      heritability.
AB  - Hair color is one of the most recognizable visual traits in European populations
      and is under strong genetic control. Here we report the results of a genome-wide
      association study meta-analysis of almost 300,000 participants of European
      descent. We identified 123 autosomal and one X-chromosome loci significantly
      associated with hair color; all but 13 are novel. Collectively, single-nucleotide
      polymorphisms associated with hair color within these loci explain 34.6% of red
      hair, 24.8% of blond hair, and 26.1% of black hair heritability in the study
      populations. These results confirm the polygenic nature of complex phenotypes and
      improve our understanding of melanin pigment metabolism in humans.

PMID- 29662171
TI  - Fatal demyelinating disease is induced by monocyte-derived macrophages in the
      absence of TGF-beta signaling.
AB  - The cytokine transforming growth factor-beta (TGF-beta) regulates the development
      and homeostasis of several tissue-resident macrophage populations, including
      microglia. TGF-beta is not critical for microglia survival but is required for
      the maintenance of the microglia-specific homeostatic gene signature1,2. Under
      defined host conditions, circulating monocytes can compete for the microglial
      niche and give rise to long-lived monocyte-derived macrophages residing in the
      central nervous system (CNS)3-5. Whether monocytes require TGF-beta for
      colonization of the microglial niche and maintenance of CNS integrity is unknown.
      We found that abrogation of TGF-beta signaling in CX3CR1+ monocyte-derived
      macrophages led to rapid onset of a progressive and fatal demyelinating motor
      disease characterized by myelin-laden giant macrophages throughout the spinal
      cord. Tgfbr2-deficient macrophages were characterized by high expression of genes
      encoding proteins involved in antigen presentation, inflammation and
      phagocytosis. TGF-beta is thus crucial for the functional integration of
      monocytes into the CNS microenvironment.

PMID- 29662170
TI  - c-Maf controls immune responses by regulating disease-specific gene networks and
      repressing IL-2 in CD4+ T cells.
AB  - The transcription factor c-Maf induces the anti-inflammatory cytokine IL-10 in
      CD4+ T cells in vitro. However, the global effects of c-Maf on diverse immune
      responses in vivo are unknown. Here we found that c-Maf regulated IL-10
      production in CD4+ T cells in disease models involving the TH1 subset of helper T
      cells (malaria), TH2 cells (allergy) and TH17 cells (autoimmunity) in vivo.
      Although mice with c-Maf deficiency targeted to T cells showed greater pathology
      in TH1 and TH2 responses, TH17 cell-mediated pathology was reduced in this
      context, with an accompanying decrease in TH17 cells and increase in Foxp3+
      regulatory T cells. Bivariate genomic footprinting elucidated the c-Maf
      transcription-factor network, including enhanced activity of NFAT; this led to
      the identification and validation of c-Maf as a negative regulator of IL-2. The
      decreased expression of the gene encoding the transcription factor RORgammat
      (Rorc) that resulted from c-Maf deficiency was dependent on IL-2, which explained
      the in vivo observations. Thus, c-Maf is a positive and negative regulator of the
      expression of cytokine-encoding genes, with context-specific effects that allow
      each immune response to occur in a controlled yet effective manner.

PMID- 29662172
TI  - Monomeric TCRs drive T cell antigen recognition.
AB  - T cell antigen recognition requires T cell antigen receptors (TCRs) engaging MHC
      embedded antigenic peptides (pMHCs) within the contact region of a T cell with
      its conjugated antigen-presenting cell. Despite micromolar TCR:pMHC affinities, T
      cells respond to even a single antigenic pMHC, and higher-order TCRs have been
      postulated to maintain high antigen sensitivity and trigger signaling. We
      interrogated the stoichiometry of TCRs and their associated CD3 subunits on the
      surface of living T cells through single-molecule brightness and single-molecule
      coincidence analysis, photon-antibunching-based fluorescence correlation
      spectroscopy and Forster resonance energy transfer measurements. We found
      exclusively monomeric TCR-CD3 complexes driving the recognition of antigenic
      pMHCs, which underscores the exceptional capacity of single TCR-CD3 complexes to
      elicit robust intracellular signaling.

PMID- 29662174
TI  - Mitochondrial OXPHOS complex assembly lines.

PMID- 29662173
TI  - Counter-rotational cell flows drive morphological and cell fate asymmetries in
      mammalian hair follicles.
AB  - Organ morphogenesis is a complex process coordinated by cell specification,
      epithelial-mesenchymal interactions and tissue polarity. A striking example is
      the pattern of regularly spaced, globally aligned mammalian hair follicles, which
      emerges through epidermal-dermal signaling and planar polarized morphogenesis.
      Here, using live-imaging, we discover that developing hair follicles polarize
      through dramatic cell rearrangements organized in a counter-rotational pattern of
      cell flows. Upon hair placode induction, Shh signaling specifies a radial pattern
      of progenitor fates that, together with planar cell polarity, induce counter
      rotational rearrangements through myosin and ROCK-dependent polarized neighbour
      exchanges. Importantly, these cell rearrangements also establish cell fate
      asymmetry by repositioning radial progenitors along the anterior-posterior axis.
      These movements concurrently displace associated mesenchymal cells, which then
      signal asymmetrically to maintain polarized cell fates. Our results demonstrate
      how spatial patterning and tissue polarity generate an unexpected collective cell
      behaviour that in turn, establishes both morphological and cell fate asymmetry.

PMID- 29662175
TI  - Pluripotency transcription factors and Tet1/2 maintain Brd4-independent stem cell
      identity.
AB  - A robust network of transcription factors and an open chromatin landscape are
      hallmarks of the naive pluripotent state. Recently, the acetyllysine reader Brd4
      has been implicated in stem cell maintenance, but the relative contribution of
      Brd4 to pluripotency remains unclear. Here, we show that Brd4 is dispensable for
      self-renewal and pluripotency of embryonic stem cells (ESCs). When maintained in
      their ground state, ESCs retain transcription factor binding and chromatin
      accessibility independent of Brd4 function or expression. In metastable ESCs,
      Brd4 independence can be achieved by increased expression of pluripotency
      transcription factors, including STAT3, Nanog or Klf4, so long as the DNA
      methylcytosine oxidases Tet1 and Tet2 are present. These data reveal that Brd4 is
      not essential for ESC self-renewal. Rather, the levels of pluripotency
      transcription factor abundance and Tet1/2 function determine the extent to which
      bromodomain recognition of protein acetylation contributes to the maintenance of
      gene expression and cell identity.

PMID- 29662177
TI  - Brd4-independence in ground state pluripotency.

PMID- 29662176
TI  - Cancer-cell-secreted exosomal miR-105 promotes tumour growth through the MYC
      dependent metabolic reprogramming of stromal cells.
AB  - Cancer and other cells residing in the same niche engage various modes of
      interactions to synchronize and buffer the negative effects of environmental
      changes. Extracellular microRNAs (miRNAs) have recently been implicated in the
      intercellular crosstalk. Here we show a mechanistic model involving breast-cancer
      secreted, extracellular-vesicle-encapsulated miR-105, which is induced by the
      oncoprotein MYC in cancer cells and, in turn, activates MYC signalling in cancer
      associated fibroblasts (CAFs) to induce a metabolic program. This results in the
      capacity of CAFs to display different metabolic features in response to changes
      in the metabolic environment. When nutrients are sufficient, miR-105-reprogrammed
      CAFs enhance glucose and glutamine metabolism to fuel adjacent cancer cells. When
      nutrient levels are low and metabolic by-products accumulate, these CAFs detoxify
      metabolic wastes, including lactic acid and ammonium, by converting them into
      energy-rich metabolites. Thus, the miR-105-mediated metabolic reprogramming of
      stromal cells contributes to sustained tumour growth by conditioning the shared
      metabolic environment.

PMID- 29662178
TI  - Defining essential genes for human pluripotent stem cells by CRISPR-Cas9
      screening in haploid cells.
AB  - The maintenance of pluripotency requires coordinated expression of a set of
      essential genes. Using our recently established haploid human pluripotent stem
      cells (hPSCs), we generated a genome-wide loss-of-function library targeting
      18,166 protein-coding genes to define the essential genes in hPSCs. With this we
      could allude to an intrinsic bias of essentiality across cellular compartments,
      uncover two opposing roles for tumour suppressor genes and link autosomal
      recessive disorders with growth-retardation phenotypes to early embryogenesis.
      hPSC-enriched essential genes mainly encode transcription factors and proteins
      related to cell-cycle and DNA-repair, revealing that a quarter of the nuclear
      factors are essential for normal growth. Our screen also led to the
      identification of growth-restricting genes whose loss of function provides a
      growth advantage to hPSCs, highlighting the role of the P53-mTOR pathway in this
      context. Overall, we have constructed an atlas of essential and growth
      restricting genes in hPSCs, revealing key aspects of cellular essentiality and
      providing a reference for future studies on human pluripotency.

PMID- 29662179
TI  - Spatial orchestration of mitochondrial translation and OXPHOS complex assembly.
AB  - Oxidative phosphorylation (OXPHOS) is vital for the regeneration of the vast
      majority of ATP in eukaryotic cells 1 . OXPHOS is carried out by large multi
      subunit protein complexes in the cristae membranes, which are invaginations of
      the mitochondrial inner membrane. The OXPHOS complexes are a mix of subunits
      encoded in the nuclear and mitochondrial genomes. Thus, the assembly of these
      dual-origin complexes is an enormous logistical challenge for the cell. Using
      super-resolution microscopy (nanoscopy) and quantitative cryo-immunogold electron
      microscopy, we determined where specific transcripts are translated and where
      distinct assembly steps of the dual-origin complexes in the yeast Saccharomyces
      cerevisiae occur. Our data indicate that the mitochondrially encoded proteins of
      complex III and complex IV are preferentially inserted in different sites of the
      inner membrane than those of complex V. We further demonstrate that the early,
      but not the late, assembly steps of complex III and complex IV occur
      preferentially in the inner boundary membrane. By contrast, all steps of complex
      V assembly occur mainly in the cristae membranes. Thus, OXPHOS complex assembly
      is spatially well orchestrated, probably representing an unappreciated regulatory
      layer in mitochondrial biogenesis.

PMID- 29662180
TI  - MYC sets a tumour-stroma metabolic loop.

PMID- 29662181
TI  - Author Correction: Niche harmony search algorithm for detecting complex disease
      associated high-order SNP combinations.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 29662183
TI  - The peptide D-list.

PMID- 29662182
TI  - Spotting the signal.

PMID- 29662184
TI  - Fueled by light.

PMID- 29662185
TI  - Structure in sequence.

PMID- 29662186
TI  - Understanding the Pro/N-end rule pathway.

PMID- 29662187
TI  - Designing macrocyclic disulfide-rich peptides for biotechnological applications.
AB  - Bioactive peptides have potential as drug leads, but turning them into drugs is a
      challenge because of their typically poor metabolic stability. Molecular grafting
      is one approach to stabilizing and constraining peptides and involves melding a
      bioactive peptide sequence onto a suitable molecular scaffold. This method has
      the benefit of improving the stability of the bioactive peptide lead and
      potentially expanding its functionality. Here we step through the molecular
      grafting process and describe its successes and limitations. So far, molecular
      grafting has been successfully used to improve the stability of peptide drug
      leads, to enhance conformational rigidity, to facilitate delivery to
      intracellular targets, and in some cases to increase efficacy in oral
      administration. Although applications of molecular grafting have focused mainly
      on therapeutic applications, including those for pain, metabolic disease, and
      cancer, its potential uses are much broader, and we hope this Perspective will
      inspire wider applications of this molecular design tool in biotechnology.

PMID- 29662188
TI  - Author Correction: Gender bias in clinicians' pathologization of atypical
      sexuality: a randomized controlled trial with mental health professionals.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 29662189
TI  - AKT as a key target for growth promoting functions of neutral ceramidase in colon
      cancer cells.
AB  - Despite advances in the field, colorectal cancer (CRC) remains a leading cause of
      cancer-related mortality worldwide. Research into bioactive sphingolipids over
      the past two decades has played an important role in increasing our understanding
      of the pathogenesis and therapeutics of CRC. In the complex metabolic network of
      sphingolipids, ceramidases (CDases) have a key function. These enzymes hydrolyze
      ceramides into sphingosine (SPH) which in turn is phosphorylated by sphingosine
      kinases (SK) 1 and 2 to generate sphingosine-1 phosphate (S1P). Importantly, we
      have recently shown that inhibition of neutral CDase (nCDase) induces an increase
      of ceramide in colon cancer cells which decreases cellular growth, increases
      apoptosis and modulates the WNT/beta-catenin pathway. We have also shown that the
      deletion of nCDase protected mice from the onset and progression of colorectal
      cancer in the AOM carcinogen model. Here, we demonstrate that AKT is a key target
      for the growth suppressing functions of ceramide. The results show that
      inhibition of nCDase activates GSK3beta through dephosphorylation, and thus is
      required for the subsequent phosphorylation and degradation of beta-catenin. Our
      findings show that inhibition of nCDase also inhibits the basal activation status
      of AKT, and we further establish that a constitutively active AKT (AKT T308D,
      S473D; AKTDD) reverses the effect of nCDase on beta-catenin degradation.
      Functionally, the AKTDD mutant is able to overcome the growth suppressive effects
      of nCDase inhibition in CRC cells. Moreover, nCDase inhibition induces a growth
      delay of xenograft tumors from control cells, whereas xenograft tumors from
      constitutively active AKT cells become resistant to nCDase inhibition. Taken
      together, these results provide important mechanistic insight into how nCDase
      regulates cell proliferation. These findings demonstrate a heretofore
      unappreciated, but critical, role for nCDase in enabling/maintaining basal
      activation of AKT and also suggest that nCDase is a suitable novel target for
      colon cancer therapy.

PMID- 29662190
TI  - Autocrine activation of JAK2 by IL-11 promotes platinum drug resistance.
AB  - Antineoplastic platinum agents are used in first-line treatment of ovarian
      cancer, but treatment failure frequently results from platinum drug resistance.
      Emerging observations suggest a role of reactive oxygen species (ROS) in the
      resistance of cancer drugs including platinum drugs. However, the molecular link
      between ROS and cellular survival pathway is poorly understood. Using
      quantitative high-throughput combinational screen (qHTCS) and genomic sequencing,
      we show that in platinum-resistant ovarian cancer elevated ROS levels sustain
      high level of IL-11 by stimulating FRA1-mediated IL-11 expression and increased
      IL-11 causes resistance to platinum drugs by constitutively activating JAK2-STAT5
      via an autocrine mechanism. Inhibition of JAK2 by LY2784544 or IL-11 by anti-IL
      11 antibody overcomes the platinum resistance in vitro or in vivo. Significantly,
      clinic studies also confirm the activated IL-11-JAK2 pathway in platinum
      resistant ovarian cancer patients, which highly correlates with poor prognosis.
      These findings not only identify a novel ROS-IL-11-JAK2-mediated platinum
      resistance mechanism but also provide a new strategy for using LY2784544- or IL
      11-mediated immunotherapy to treat platinum-resistant ovarian cancer.

PMID- 29662191
TI  - WNT ligands control initiation and progression of human papillomavirus-driven
      squamous cell carcinoma.
AB  - Human papillomavirus (HPV)-driven cutaneous squamous cell carcinoma (cSCC) is the
      most common cancer in immunosuppressed patients. Despite indications suggesting
      that HPV promotes genomic instability during cSCC development, the molecular
      pathways underpinning HPV-driven cSCC development remain unknown. We compared the
      transcriptome of HPV-driven mouse cSCC with normal skin and observed higher
      amounts of transcripts for Porcupine and WNT ligands in cSCC, suggesting a role
      for WNT signaling in cSCC progression. We confirmed increased Porcupine
      expression in human cSCC samples. Blocking the secretion of WNT ligands by the
      Porcupine inhibitor LGK974 significantly diminished initiation and progression of
      HPV-driven cSCC. Administration of LGK974 to mice with established cSCC resulted
      in differentiation of cancer cells and significant reduction of the cancer stem
      cell compartment. Thus, WNT/beta-catenin signaling is essential for HPV-driven
      cSCC initiation and progression as well as for maintaining the cancer stem cell
      niche. Interference with WNT secretion may thus represent a promising approach
      for therapeutic intervention.

PMID- 29662192
TI  - Capillary morphogenesis gene 2 maintains gastric cancer stem-like cell phenotype
      by activating a Wnt/beta-catenin pathway.
AB  - A growing body of evidence shows that the development and progression of gastric
      cancer (GC) is mainly associated to the presence of gastric cancer stem-like
      cells (GCSLCs). However, it is unclear how GCSLC population is maintained. This
      study aimed to explore the role of capillary morphogenesis gene 2 (CMG2) in GCSLC
      maintenance and the relevance to GC progression. We found that CMG2 was highly
      expressed in GC tissues and the expression levels were associated with the
      invasion depth and lymph node metastasis of GC, and inversely correlated with the
      survival of GC patients. Sorted CMG2High GC cells preferentially clustered in
      CD44High stem-like cell population, which expressed high levels of stemness
      related genes with increased capabilities of self-renewal and tumorigenicity.
      Depletion of CMG2 gene resulted in reduction of GCSLC population with attenuated
      stemness and decrease of invasive and metastatic capabilities with subdued
      epithelial-mesenchymal transition phenotype in GC cells. Mechanistically, CMG2
      interacted with LRP6 in GCSLCs to activate a Wnt/beta-catenin pathway. Thus, our
      results demonstrate that CMG2 promotes GC progression by maintaining GCSLCs and
      can serve as a new prognostic indicator and a target for human GC therapy.

PMID- 29662193
TI  - SPAG5 promotes proliferation and suppresses apoptosis in bladder urothelial
      carcinoma by upregulating Wnt3 via activating the AKT/mTOR pathway and predicts
      poorer survival.
AB  - Sperm-associated antigen 5 (SPAG5) is involved in various biological processes.
      However, the roles of SPAG5 in bladder urothelial carcinoma (BUC) are unknown.
      This study showed that upregulation of SPAG5 was detected frequently in primary
      BUC tissues, and was associated with significantly worse survival among the 112
      patients that underwent radical cystectomy (RC). Up and downregulating the
      expression of SPAG5 enhanced or inhibited, respectively, the proliferation of BUC
      cells in vitro and in vivo, and suppressed or enhanced, respectively, apoptosis
      in vitro and in vivo. Moreover, SPAG5 increased the resistance of BUC cells to
      chemotherapy-induced apoptosis. Mechanistic investigations showed that SPAG5
      promotes proliferation and suppresses apoptosis in BUC at least partially via
      upregulating Wnt3 through activating the AKT/mTOR signaling pathway. The
      importance of the SPAG5/AKT-mTOR/Wnt3 axis identified in BUC cell models was
      confirmed via immunohistochemical analysis of a cohort of human BUC specimens
      that underwent RC. Collectively, our data suggested that in patients with BUC who
      underwent RC, high SPAG5 expression is associated with poor survival. In
      addition, targeting SPAG5 might represent a novel therapeutic strategy to improve
      the survival of patients with BUC.

PMID- 29662194
TI  - An EGFR ligand promotes EGFR-mutant but not KRAS-mutant lung cancer in vivo.
AB  - EGFR ligands (e.g., EGF and TGFA) have been shown to be clinically associated
      with poor survival in lung cancer. Since TGFA itself initiates autochthonous
      tumors in liver, breast, and pancreas but not in the lung in transgenic mice in
      vivo, it would appear that an EGFR ligand may not initiate but rather promote
      lung cancer. However, it has not been proven in vivo whether lung cancer is
      promoted by an EGFR ligand. Using transgenic mouse models conditionally
      expressing EGFRL858R or KrasG12D with TGFA (an EGFR ligand) in lung epithelium,
      we determined that TGFA promoted the growth of EGFRL858R-lung tumors in airway
      regions but not that of KrasG12D-lung tumors. Analysis of TCGA datasets
      identified DeltaNp63 and AGR2 as potential key tumor-promoting regulators, which
      were highly induced in the TGFA-induced EGFRL858R-lung tumors. The expression of
      AGR2 was positively correlated with the expression of TGFA in human EGFR-mutant
      lung adenocarcinomas. The expression of TGFA in human EGFR-mutant lung
      adenocarcinomas but not in the EGFR wild-type lung adenocarcinoma was associated
      with poor survival. These results suggest that targeting EGFR ligands may benefit
      patients who carry EGFR-mutant lung tumors but will not benefit patients with
      KRAS-mutant lung tumors.

PMID- 29662195
TI  - NGR (Asn-Gly-Arg)-targeted delivery of coagulase to tumor vasculature arrests
      cancer cell growth.
AB  - Induction of selective thrombosis and infarction in tumor-feeding vessels
      represents an attractive strategy to combat cancer. Here we took advantage of the
      unique coagulation properties of staphylocoagulase and genetically engineered it
      to generate a new fusion protein with novel anti-cancer properties. This novel bi
      functional protein consists of truncated coagulase (tCoa) and an NGR (GNGRAHA)
      motif that recognizes CD13 and alphavbeta3 integrin receptors, targeting it to
      tumor endothelial cells. Herein, we report that tCoa coupled by its C-terminus to
      an NGR sequence retained its normal binding activity with prothrombin and avbeta3
      integrins, as confirmed in silico and in vitro. Moreover, in vivo biodistribution
      studies demonstrated selective accumulation of FITC-labeled tCoa-NGR fusion
      proteins at the site of subcutaneously implanted PC3 tumor xenografts in nude
      mice. Notably, systemic administration of tCoa-NGR to mice bearing 4T1 mouse
      mammary xenografts or PC3 human prostate tumors resulted in a significant
      reduction in tumor growth. These anti-tumor effects were accompanied by massive
      thrombotic occlusion of small and large tumor vessels, tumor infarction and tumor
      cell death. From these findings, we propose tCoa-NGR mediated tumor infarction as
      a novel and promising anti-cancer strategy targeting both CD13 and integrin
      alphavbeta3 positive tumor neovasculature.

PMID- 29662196
TI  - Tocopherols inhibit esophageal carcinogenesis through attenuating NF-kappaB
      activation and CXCR3-mediated inflammation.
AB  - Esophageal cancer is one of the common causes of cancer mortality in the world.
      The predominant histological subtype, esophageal squamous cell carcinoma (ESCC),
      often results in poor prognosis due to the lack of effective approaches for the
      early diagnosis and treatment, highlighting the need for preventive intervention
      against this disease. Here we report that dietary tocopherols significantly
      prevents esophageal carcinogenesis by inhibiting the activation of NF-kappaB and
      the subsequent interaction of chemokine CXCL9/10/11 with their receptor CXCR3 in
      ESCC induced by N-nitrosomethylbenzylamine (NMBA) in murine models. Dietary
      supplementation with 0.15% alpha-tocopherol (alpha-T), delta-tocopherol (delta
      T), or gamma-tocopherol rich mixture (gamma-TmT) markedly suppressed the
      production of pro-inflammatory cytokines, as well as the induction of CXCR3+
      effector T cells (CD4+ Th1 and CD8+ CTLs) infiltration, especially at the early
      stage of carcinogenesis. In experiments in vivo and in vitro, these events were
      tightly correlated with the blockade of NF-kappaB activation. Our results show
      that tocopherols decrease carcinogenesis through inhibiting NF-kappaB and CXCR3
      signaling, as well as related inflammation in early premalignant lesions. This
      pathway may offer a novel target for chemoprevention of esophageal cancer.

PMID- 29662197
TI  - MEKK2 and MEKK3 suppress Hedgehog pathway-dependent medulloblastoma by inhibiting
      GLI1 function.
AB  - Hedgehog (Hh) pathway plays a pivotal role in diverse aspects of development and
      postnatal physiology. Perturbation of Hh signaling and activation of GLI1 (glioma
      associated oncogene 1), a dedicated transcription factor for Hh pathway, are
      highly associated with several cancers, such as medulloblastoma and basal cell
      carcinoma. Dynamic and precise control of GLI1 activity is thus important to
      ensure proper homeostasis and tumorigenesis. Here we show that MEKK2 (MAP3K2) and
      MEKK3 (MAP3K3) inhibit GLI1 transcriptional activity and oncogenic function
      through phosphorylation on multiple Ser/Thr sites of GLI1, which reduces GLI1
      protein stability, DNA-binding ability, and increases the association of GLI1
      with SUFU. Interestingly, MEKK2 and MEKK3 are responsible for FGF2-mediated
      inhibition on Hh signaling. Moreover, expression of MEKK2 and MEKK3 inhibits
      medulloblastoma cell proliferation and negatively correlates with Hh pathway
      activity in medulloblastoma clinical samples. Together, these findings reveal a
      novel noncanonical GLI1 regulation and provide a potential therapeutic target for
      the treatment of cancers with aberrant Hh pathway activation, such as
      medulloblastoma.

PMID- 29662198
TI  - The miR-106b-25 cluster mediates breast tumor initiation through activation of
      NOTCH1 via direct repression of NEDD4L.
AB  - Tumor-initiating cells (TIC) represent a subset of tumor cells with increased
      self-renewal capability. TICs display resistance to frontline cancer treatment
      and retain the ability to repopulate a tumor after therapy, leading to cancer
      relapse. NOTCH signaling has been identified as an important driver of the TIC
      population, yet mechanisms governing regulation of this pathway in cancer remain
      to be fully elucidated. Here we identify a novel mechanism of NOTCH regulation
      and TIC induction in breast cancer via the miR-106b-25 miRNA cluster. We show
      that the miR-106b-25 cluster upregulates NOTCH1 in multiple breast cancer cell
      lines, representing both estrogen receptor (ER+) and triple negative breast
      cancer (TNBC) through direct repression of the E3 ubiquitin ligase, NEDD4L. We
      further show that upregulation of NOTCH1 is necessary for TIC induction
      downstream of miR-106b-25 in both ER + and TNBC breast cancer cells, and that re
      expression of NEDD4L is sufficient to reverse miR106b-25-mediated NOTCH1
      upregulation and TIC induction. Importantly, we demonstrate a significant
      positive correlation between miR-106b-25 and NOTCH1 protein, yet a significant
      inverse correlation between miR-106b-25 and NEDD4L mRNA in human breast cancer,
      suggesting a critical role for the miR106b-25/NEDD4L/NOTCH1 axis in the disease.
      Further, we show for the first time that NEDD4L expression alone is significantly
      associated with a better relapse-free prognosis for breast cancer patients. These
      data expand our knowledge of the mechanisms underlying NOTCH activation and TIC
      induction in breast cancer, and may provide new avenues for the development of
      therapies targeting this resistant subset of tumor cells.

PMID- 29662199
TI  - A single injection of crystallizable fragment domain-modified antibodies elicits
      durable protection from SHIV infection.
AB  - In the absence of an effective and safe vaccine against HIV-1, the administration
      of broadly neutralizing antibodies (bNAbs) represents a logical alternative
      approach to prevent virus transmission. Here, we introduced two mutations
      encoding amino acid substitutions (M428L and N434S, collectively referred to as
      'LS') into the genes encoding the crystallizable fragment domains of the highly
      potent HIV-specific 3BNC117 and 10-1074 bNAbs to increase their half-lives and
      evaluated their efficacy in blocking infection following repeated low-dose
      mucosal challenges of rhesus macaques (Macaca mulatta) with the tier 2 SHIVAD8
      EO. A single intravenous infusion of 10-1074-LS monoclonal antibodies markedly
      delayed virus acquisition for 18 to 37 weeks (median, 27 weeks), whereas the
      protective effect of the 3BNC117-LS bNAb was more modest (provided protection for
      11-23 weeks; median, 17 weeks). Serum concentrations of the 10-1074-LS monoclonal
      antibody gradually declined and became undetectable in all recipients between
      weeks 26 and 41, whereas the 3BNC117-LS bNAb exhibited a shorter half-life. To
      model immunoprophylaxis against genetically diverse and/or neutralization
      resistant HIV-1 strains, a combination of the 3BNC117-LS plus 10-1074-LS
      monoclonal antibodies was injected into macaques via the more clinically relevant
      subcutaneous route. Even though the administered mixture contained an amount of
      each bNAb that was nearly threefold less than the quantity of the single
      monoclonal antibody in the intravenous injections, the monoclonal antibody
      combination still protected macaques for a median of 20 weeks. The extended
      period of protection observed in macaques for the 3BNC117-LS plus 10-1074-LS
      combination could translate into an effective semiannual or annual
      immunoprophylaxis regimen for preventing HIV-1 infections in humans.

PMID- 29662200
TI  - Targeting sphingosine-1-phosphate lyase as an anabolic therapy for bone loss.
AB  - Sphingosine-1-phosphate (S1P) signaling influences bone metabolism, but its
      therapeutic potential in bone disorders has remained unexplored. We show that
      raising S1P levels in adult mice through conditionally deleting or
      pharmacologically inhibiting S1P lyase, the sole enzyme responsible for
      irreversibly degrading S1P, markedly increased bone formation, mass and strength
      and substantially decreased white adipose tissue. S1P signaling through S1P2
      potently stimulated osteoblastogenesis at the expense of adipogenesis by
      inversely regulating osterix and PPAR-gamma, and it simultaneously inhibited
      osteoclastogenesis by inducing osteoprotegerin through newly discovered p38
      GSK3beta-beta-catenin and WNT5A-LRP5 pathways. Accordingly, S1P2-deficient mice
      were osteopenic and obese. In ovariectomy-induced osteopenia, S1P lyase
      inhibition was as effective as intermittent parathyroid hormone (iPTH) treatment
      in increasing bone mass and was superior to iPTH in enhancing bone strength.
      Furthermore, lyase inhibition in mice successfully corrected severe genetic
      osteoporosis caused by osteoprotegerin deficiency. Human data from 4,091
      participants of the SHIP-Trend population-based study revealed a positive
      association between serum levels of S1P and bone formation markers, but not
      resorption markers. Furthermore, serum S1P levels were positively associated with
      serum calcium , negatively with PTH , and curvilinearly with body mass index.
      Bone stiffness, as determined through quantitative ultrasound, was inversely
      related to levels of both S1P and the bone formation marker PINP, suggesting that
      S1P stimulates osteoanabolic activity to counteract decreasing bone quality. S1P
      based drugs should be considered as a promising therapeutic avenue for the
      treatment of osteoporotic diseases.

PMID- 29662201
TI  - Differential glucose requirement in skin homeostasis and injury identifies a
      therapeutic target for psoriasis.
AB  - Proliferating cells, compared with quiescent cells, are more dependent on glucose
      for their growth. Although glucose transport in keratinocytes is mediated largely
      by the Glut1 facilitative transporter, we found that keratinocyte-specific
      ablation of Glut1 did not compromise mouse skin development and homeostasis. Ex
      vivo metabolic profiling revealed altered sphingolipid, hexose, amino acid, and
      nucleotide metabolism in Glut1-deficient keratinocytes, thus suggesting metabolic
      adaptation. However, cultured Glut1-deficient keratinocytes displayed metabolic
      and oxidative stress and impaired proliferation. Similarly, Glut1 deficiency
      impaired in vivo keratinocyte proliferation and migration within wounded or UV
      damaged mouse skin. Notably, both genetic and pharmacological Glut1 inactivation
      decreased hyperplasia in mouse models of psoriasis-like disease. Topical
      application of a Glut1 inhibitor also decreased inflammation in these models.
      Glut1 inhibition decreased the expression of pathology-associated genes in human
      psoriatic skin organoids. Thus, Glut1 is selectively required for injury- and
      inflammation-associated keratinocyte proliferation, and its inhibition offers a
      novel treatment strategy for psoriasis.

PMID- 29662202
TI  - Stimulation of entorhinal cortex-dentate gyrus circuitry is antidepressive.
AB  - Major depressive disorder (MDD) is considered a 'circuitopathy', and brain
      stimulation therapies hold promise for ameliorating MDD symptoms, including
      hippocampal dysfunction. It is unknown whether stimulation of upstream
      hippocampal circuitry, such as the entorhinal cortex (Ent), is antidepressive,
      although Ent stimulation improves learning and memory in mice and humans. Here we
      show that molecular targeting (Ent-specific knockdown of a psychosocial stress
      induced protein) and chemogenetic stimulation of Ent neurons induce
      antidepressive-like effects in mice. Mechanistically, we show that Ent
      stimulation-induced antidepressive-like behavior relies on the generation of new
      hippocampal neurons. Thus, controlled stimulation of Ent hippocampal afferents is
      antidepressive via increased hippocampal neurogenesis. These findings emphasize
      the power and potential of Ent glutamatergic afferent stimulation-previously well
      known for its ability to influence learning and memory-for MDD treatment.

PMID- 29662203
TI  - Potent antitumor efficacy of anti-GD2 CAR T cells in H3-K27M+ diffuse midline
      gliomas.
AB  - Diffuse intrinsic pontine glioma (DIPG) and other diffuse midline gliomas (DMGs)
      with mutated histone H3 K27M (H3-K27M)1-5 are aggressive and universally fatal
      pediatric brain cancers 6 . Chimeric antigen receptor (CAR)-expressing T cells
      have mediated impressive clinical activity in B cell malignancies7-10, and recent
      results suggest benefit in central nervous system malignancies11-13. Here, we
      report that patient-derived H3-K27M-mutant glioma cell cultures exhibit uniform,
      high expression of the disialoganglioside GD2. Anti-GD2 CAR T cells incorporating
      a 4-1BBz costimulatory domain 14 demonstrated robust antigen-dependent cytokine
      generation and killing of DMG cells in vitro. In five independent patient-derived
      H3-K27M+ DMG orthotopic xenograft models, systemic administration of GD2-targeted
      CAR T cells cleared engrafted tumors except for a small number of residual GD2lo
      glioma cells. To date, GD2-targeted CAR T cells have been well tolerated in
      clinical trials15-17. Although GD2-targeted CAR T cell administration was
      tolerated in the majority of mice bearing orthotopic xenografts, peritumoral
      neuroinflammation during the acute phase of antitumor activity resulted in
      hydrocephalus that was lethal in a fraction of animals. Given the precarious
      neuroanatomical location of midline gliomas, careful monitoring and aggressive
      neurointensive care management will be required for human translation. With a
      cautious multidisciplinary clinical approach, GD2-targeted CAR T cell therapy for
      H3-K27M+ diffuse gliomas of pons, thalamus and spinal cord could prove
      transformative for these lethal childhood cancers.

PMID- 29662205
TI  - Neural repair: Getting back on your hindlimbs.

PMID- 29662206
TI  - Understanding the quantum nature of low-energy C(3P j ) + He inelastic
      collisions.
AB  - Inelastic collisions that occur between open-shell atoms and other atoms or
      molecules, and that promote a spin-orbit transition, involve multiple interaction
      potentials. They are non-adiabatic by nature and cannot be described within the
      Born-Oppenheimer approximation; in particular, their theoretical modelling
      becomes very challenging when the collision energies have values comparable to
      the spin-orbit splitting. Here we study inelastic collisions between carbon in
      its ground state C(3Pj=0) and helium atoms-at collision energies in the vicinity
      of spin-orbit excitation thresholds (~0.2 and 0.5 kJ mol-1)-that result in spin
      orbit excitation to C(3Pj=1) and C(3Pj=2). State-to-state integral cross-sections
      are obtained from crossed-beam experiments with a beam source that provides an
      almost pure beam of C(3Pj=0) . We observe very good agreement between
      experimental and theoretical results (acquired using newly calculated potential
      energy curves), which validates our characterization of the quantum dynamical
      resonances that are observed. Rate coefficients at very low temperatures suitable
      for chemical modelling of the interstellar medium are also calculated.

PMID- 29662207
TI  - Tracing the 'ninth sulfur' of the nitrogenase cofactor via a semi-synthetic
      approach.
AB  - The M-cluster is the [(homocitrate)MoFe7S9C] active site of nitrogenase that is
      derived from an 8Fe core assembled viacoupling and rearrangement of two [Fe4S4]
      clusters concomitant with the insertion of an interstitial carbon and a 'ninth
      sulfur'. Combining synthetic [Fe4S4] clusters with an assembly protein template,
      here we show that sulfite can give rise to the ninth sulfur that is incorporated
      in the catalytically important belt region of the cofactor after the radical S
      adenosyl-L-methionine-dependent carbide insertion and the concurrent 8Fe-core
      rearrangement have already taken place. Based on the differential reactivity of
      the formed cluster species, we also propose a new [Fe8S8C] cluster intermediate,
      the L*-cluster, which is similar to the [Fe8S9C] L-cluster, but lacks the ninth
      sulfur from sulfite. This work provides a semi-synthetic tool for protein
      reconstitution that could be widely applicable for the functional analysis of
      other FeS systems.

PMID- 29662208
TI  - Cold quantum-controlled rotationally inelastic scattering of HD with H2 and D2
      reveals collisional partner reorientation.
AB  - Molecular interactions are best probed by scattering experiments. Interpretation
      of these studies has been limited by lack of control over the quantum states of
      the incoming collision partners. We report here the rotationally inelastic
      collisions of quantum-state prepared deuterium hydride (HD) with H2 and D2 using
      a method that provides an improved control over the input states. HD was
      coexpanded with its partner in a single supersonic beam, which reduced the
      collision temperature to 0-5 K, and thereby restricted the involved incoming
      partial waves to s and p. By preparing HD with its bond axis preferentially
      aligned parallel and perpendicular to the relative velocity of the colliding
      partners, we observed that the rotational relaxation of HD depends strongly on
      the initial bond-axis orientation. We developed a partial-wave analysis that
      conclusively demonstrates that the scattering mechanism involves the exchange of
      internal angular momentum between the colliding partners. The striking
      differences between H2/HD and D2/HD scattering suggest the presence of
      anisotropically sensitive resonances.

PMID- 29662204
TI  - Feeding circuit development and early-life influences on future feeding
      behaviour.
AB  - A wide range of maternal exposures - undernutrition, obesity, diabetes, stress
      and infection - are associated with an increased risk of metabolic disease in
      offspring. Developmental influences can cause persistent structural changes in
      hypothalamic circuits regulating food intake in the service of energy balance.
      The physiological relevance of these alterations has been called into question
      because maternal impacts on daily caloric intake do not persist to adulthood.
      Recent behavioural and epidemiological studies in humans provide evidence that
      the relative contribution of appetitive traits related to satiety, reward and the
      emotional aspects of food intake regulation changes across the lifespan. This
      Opinion article outlines a neurodevelopmental framework to explore the
      possibility that crosstalk between developing circuits regulating different
      modalities of food intake shapes future behavioural responses to environmental
      challenges.

PMID- 29662209
TI  - Dynamic coupling between conformations and nucleotide states in DNA gyrase.
AB  - Gyrase is an essential bacterial molecular motor that supercoils DNA using a
      conformational cycle in which chiral wrapping of > 100 base pairs confers
      directionality on topoisomerization. To understand the mechanism of this
      nucleoprotein machine, global structural transitions must be mapped onto the
      nucleotide cycle of ATP binding, hydrolysis and product release. Here we
      investigate coupling mechanisms using single-molecule tracking of DNA rotation
      and contraction during Escherichia coli gyrase activity under varying nucleotide
      conditions. We find that ADP must be exchanged for ATP to drive the rate-limiting
      remodeling transition that generates the chiral wrap. ATP hydrolysis accelerates
      subsequent duplex strand passage and is required for resetting the enzyme and
      recapturing transiently released DNA. Our measurements suggest how gyrase
      coordinates DNA rearrangements with the dynamics of its ATP-driven protein gate,
      how the motor minimizes futile cycles of ATP hydrolysis and how gyrase may
      respond to changing cellular energy levels to link gene expression with
      metabolism.

PMID- 29662210
TI  - Genome-wide mutant profiling predicts the mechanism of a Lipid II binding
      antibiotic.
AB  - Identifying targets of antibacterial compounds remains a challenging step in the
      development of antibiotics. We have developed a two-pronged functional genomics
      approach to predict mechanism of action that uses mutant fitness data from
      antibiotic-treated transposon libraries containing both upregulation and
      inactivation mutants. We treated a Staphylococcus aureus transposon library
      containing 690,000 unique insertions with 32 antibiotics. Upregulation signatures
      identified from directional biases in insertions revealed known molecular targets
      and resistance mechanisms for the majority of these. Because single-gene
      upregulation does not always confer resistance, we used a complementary machine
      learning approach to predict the mechanism from inactivation mutant fitness
      profiles. This approach suggested the cell wall precursor Lipid II as the
      molecular target of the lysocins, a mechanism we have confirmed. We conclude that
      docking to membrane-anchored Lipid II precedes the selective bacteriolysis that
      distinguishes these lytic natural products, showing the utility of our approach
      for nominating the antibiotic mechanism of action.

PMID- 29662212
TI  - Yet another reason to walk instead of drive.

PMID- 29662211
TI  - Synthesis, structure and reaction chemistry of a nucleophilic aluminyl anion.
AB  - The reactivity of aluminium compounds is dominated by their electron deficiency
      and consequent electrophilicity; these compounds are archetypal Lewis acids
      (electron-pair acceptors). The main industrial roles of aluminium, and classical
      methods of synthesizing aluminium-element bonds (for example, hydroalumination
      and metathesis), draw on the electron deficiency of species of the type AlR3 and
      AlCl31,2. Whereas aluminates, [AlR4]-, are well known, the idea of reversing
      polarity and using an aluminium reagent as the nucleophilic partner in bond
      forming substitution reactions is unprecedented, owing to the fact that low
      valent aluminium anions analogous to nitrogen-, carbon- and boron-centred
      reagents of the types [NX2]-, [CX3]- and [BX2]- are unknown3-5. Aluminium
      compounds in the +1 oxidation state are known, but are thermodynamically unstable
      with respect to disproportionation. Compounds of this type are typically
      oligomeric6-8, although monomeric systems that possess a metal-centred lone pair,
      such as Al(Nacnac)Dipp (where (Nacnac)Dipp = (NDippCR)2CH and R =  t Bu, Me; Dipp
      = 2,6- i Pr2C6H3), have also been reported9,10. Coordination of these species,
      and also of (eta5-C5Me5)Al, to a range of Lewis acids has been observed11-13, but
      their primary mode of reactivity involves facile oxidative addition to generate
      Al(III) species6-8,14-16. Here we report the synthesis, structure and reaction
      chemistry of an anionic aluminium(I) nucleophile, the dimethylxanthene-stabilized
      potassium aluminyl [K{Al(NON)}]2 (NON = 4,5-bis(2,6-diisopropylanilido)-2,7-di
      tert-butyl-9,9-dimethylxanthene). This species displays unprecedented reactivity
      in the formation of aluminium-element covalent bonds and in the C-H oxidative
      addition of benzene, suggesting that it could find further use in both metal
      carbon and metal-metal bond-forming reactions.

PMID- 29662213
TI  - Encoding of error and learning to correct that error by the Purkinje cells of the
      cerebellum.
AB  - The primary output cells of the cerebellar cortex, Purkinje cells, make kinematic
      predictions about ongoing movements via high-frequency simple spikes, but receive
      sensory error information about that movement via low-frequency complex spikes
      (CS). How is the vector space of sensory errors encoded by this low-frequency
      signal? Here we measured Purkinje cell activity in the oculomotor vermis of
      animals during saccades, then followed the chain of events from experience of
      visual error, generation of CS, modulation of simple spikes, and ultimately
      change in motor output. We found that while error direction affected the
      probability of CS, error magnitude altered its temporal distribution. Production
      of CS changed the simple spikes on the next trial, but regardless of the actual
      visual error, this change biased the movement only along a vector that was
      parallel to the Purkinje cell's preferred error. From these results, we inferred
      the anatomy of a sensory-to-motor adaptive controller that transformed visual
      error vectors into motor-corrections.

PMID- 29662215
TI  - Heartless beat or beatless heart?

PMID- 29662214
TI  - Locomotor activity modulates associative learning in mouse cerebellum.
AB  - Changes in behavioral state can profoundly influence brain function. Here we show
      that behavioral state modulates performance in delay eyeblink conditioning, a
      cerebellum-dependent form of associative learning. Increased locomotor speed in
      head-fixed mice drove earlier onset of learning and trial-by-trial enhancement of
      learned responses that were dissociable from changes in arousal and independent
      of sensory modality. Eyelid responses evoked by optogenetic stimulation of mossy
      fiber inputs to the cerebellum, but not at sites downstream, were positively
      modulated by ongoing locomotion. Substituting prolonged, low-intensity
      optogenetic mossy fiber stimulation for locomotion was sufficient to enhance
      conditioned responses. Our results suggest that locomotor activity modulates
      delay eyeblink conditioning through increased activation of the mossy fiber
      pathway within the cerebellum. Taken together, these results provide evidence for
      a novel role for behavioral state modulation in associative learning and suggest
      a potential mechanism through which engaging in movement can improve an
      individual's ability to learn.

PMID- 29662217
TI  - The functional organization of cortical feedback inputs to primary visual cortex.
AB  - Cortical feedback is thought to mediate cognitive processes like attention,
      prediction, and awareness. Understanding its function requires identifying the
      organizational logic of feedback axons relaying different signals. We measured
      retinotopic specificity in inputs from the lateromedial visual area in mouse
      primary visual cortex (V1) by mapping receptive fields in feedback boutons and
      relating them to those of neurons in their vicinity. Lateromedial visual area
      inputs in layer 1 targeted, on average, retinotopically matched locations in V1,
      but many of them relayed distal visual information. Orientation-selective axons
      overspread around the retinotopically matched location perpendicularly to their
      preferred orientation. Direction-selective axons were biased to visual areas
      shifted from the retinotopically matched position along the angle of their
      antipreferred direction. Our results show that feedback inputs show tuning
      dependent retinotopic specificity. By targeting locations that would be activated
      by stimuli orthogonal to or opposite to a cell's own tuning, feedback could
      potentially enhance visual representations in time and space.

PMID- 29662216
TI  - Cortical drive and thalamic feed-forward inhibition control thalamic output
      synchrony during absence seizures.
AB  - Behaviorally and pathologically relevant cortico-thalamo-cortical oscillations
      are driven by diverse interacting cell-intrinsic and synaptic processes. However,
      the mechanism that gives rise to the paroxysmal oscillations of absence seizures
      (ASs) remains unknown. Here we report that, during ASs in behaving animals,
      cortico-thalamic excitation drives thalamic firing by preferentially eliciting
      tonic rather than T-type Ca 2+ channel (T-channel)-dependent burst firing in
      thalamocortical (TC) neurons and by temporally framing thalamic output via
      feedforward reticular thalamic (NRT)-to-TC neuron inhibition. In TC neurons,
      overall ictal firing was markedly reduced and bursts rarely occurred. Moreover,
      blockade of T-channels in cortical and NRT neurons suppressed ASs, but such
      blockade in TC neurons had no effect on seizures or on ictal thalamic output
      synchrony. These results demonstrate ictal bidirectional cortico-thalamic
      communications and provide the first mechanistic understanding of cortico-thalamo
      cortical network firing dynamics during ASs in behaving animals.

PMID- 29662219
TI  - Spin-orbit torques associated with ferrimagnetic order in Pt/GdFeCo/MgO layers.
AB  - We investigate spin orbit torque (SOT) efficiencies and magnetic properties of
      Pt/GdFeCo/MgO multilayers by varying the thicknesses of GdFeCo and MgO layers.
      Our studies indicate that the ferrimagnetism in the GdFeCo alloy is considerably
      influenced by both thicknesses due to the diffusion of Gd atoms toward the MgO
      layer. Comparing to conventional Pt/ferromagnet/MgO structures, the Pt/GdFeCo/MgO
      exhibits a lower efficiency of SOTs associated with ferrimagnetic order and a
      similar magnitude of magnetic damping. The previous models that have been
      developed for rigid ferromagnets are inappropriate to analyze our experimental
      data, leading to an unphysical consequence of spin transmission larger than
      unity. Our results imply that the heavy-metal/ferrimagnet system is quite
      different from heavy-metal/ferromagnet systems in terms of magnetic dynamical
      modes, spin angular momentum transfer, and relaxation processes.

PMID- 29662218
TI  - Tapping the RNA world for therapeutics.
AB  - A recent revolution in RNA biology has led to the identification of new RNA
      classes with unanticipated functions, new types of RNA modifications, an
      unexpected multiplicity of alternative transcripts and widespread transcription
      of extragenic regions. This development in basic RNA biology has spawned a
      corresponding revolution in RNA-based strategies to generate new types of
      therapeutics. Here, I review RNA-based drug design and discuss barriers to
      broader applications and possible ways to overcome them. Because they target
      nucleic acids rather than proteins, RNA-based drugs promise to greatly extend the
      domain of 'druggable' targets beyond what can be achieved with small molecules
      and biologics.

PMID- 29662220
TI  - Uranium transport in acidic brines under reducing conditions.
AB  - The behavior of uranium in environments, ranging from those of natural systems
      responsible for the formation of uranium deposits to those of nuclear reactors
      providing 11% of the world's electricity, is governed by processes involving high
      temperature aqueous solutions. It has been well documented that uranium is mobile
      in aqueous solutions in its oxidized, U6+ state, whereas in its reduced, U4+
      state, uranium has been assumed to be immobile. Here, we present experimental
      evidence from high temperature (>100  degrees C) acidic brines that invalidates
      this assumption. Our experiments have identified a new uranium chloride species
      (UCl4 degrees ) that is more stable under reducing than oxidized conditions.
      These results indicate that uranium is mobile under reducing conditions and
      necessitate a re-evaluation of the mobility of uranium, particularly in ore
      deposit models involving this metal. Regardless of the scenario considered,
      reducing conditions can no longer be considered a guarantee of uranium
      immobility.

PMID- 29662221
TI  - Colin Groves (1942-2017).

PMID- 29662222
TI  - Function and functional redundancy in microbial systems.
AB  - Microbial communities often exhibit incredible taxonomic diversity, raising
      questions regarding the mechanisms enabling species coexistence and the role of
      this diversity in community functioning. On the one hand, many coexisting but
      taxonomically distinct microorganisms can encode the same energy-yielding
      metabolic functions, and this functional redundancy contrasts with the
      expectation that species should occupy distinct metabolic niches. On the other
      hand, the identity of taxa encoding each function can vary substantially across
      space or time with little effect on the function, and this taxonomic variability
      is frequently thought to result from ecological drift between equivalent
      organisms. Here, we synthesize the powerful paradigm emerging from these two
      patterns, connecting the roles of function, functional redundancy and taxonomy in
      microbial systems. We conclude that both patterns are unlikely to be the result
      of ecological drift, but are inevitable emergent properties of open microbial
      systems resulting mainly from biotic interactions and environmental and spatial
      processes.

PMID- 29662223
TI  - Ecological suicide in microbes.
AB  - The growth and survival of organisms often depend on interactions between them.
      In many cases, these interactions are positive and caused by a cooperative
      modification of the environment. Examples are the cooperative breakdown of
      complex nutrients in microbes or the construction of elaborate architectures in
      social insects, in which the individual profits from the collective actions of
      her peers. However, organisms can similarly display negative interactions by
      changing the environment in ways that are detrimental for them, for example by
      resource depletion or the production of toxic byproducts. Here we find an extreme
      type of negative interactions, in which Paenibacillus sp. bacteria modify the
      environmental pH to such a degree that it leads to a rapid extinction of the
      whole population, a phenomenon that we call ecological suicide. Modification of
      the pH is more pronounced at higher population densities, and thus ecological
      suicide is more likely to occur with increasing bacterial density.
      Correspondingly, promoting bacterial growth can drive populations extinct whereas
      inhibiting bacterial growth by the addition of harmful substances-such as
      antibiotics-can rescue them. Moreover, ecological suicide can cause oscillatory
      dynamics, even in single-species populations. We found ecological suicide in a
      wide variety of microbes, suggesting that it could have an important role in
      microbial ecology and evolution.

PMID- 29662224
TI  - The spatial scaling of species interaction networks.
AB  - Species-area relationships (SARs) are pivotal to understand the distribution of
      biodiversity across spatial scales. We know little, however, about how the
      network of biotic interactions in which biodiversity is embedded changes with
      spatial extent. Here we develop a new theoretical framework that enables us to
      explore how different assembly mechanisms and theoretical models affect multiple
      properties of ecological networks across space. We present a number of testable
      predictions on network-area relationships (NARs) for multi-trophic communities.
      Network structure changes as area increases because of the existence of different
      SARs across trophic levels, the preferential selection of generalist species at
      small spatial extents and the effect of dispersal limitation promoting beta
      diversity. Developing an understanding of NARs will complement the growing body
      of knowledge on SARs with potential applications in conservation ecology.
      Specifically, combined with further empirical evidence, NARs can generate
      predictions of potential effects on ecological communities of habitat loss and
      fragmentation in a changing world.

PMID- 29662225
TI  - Reply to 'Whaling catch data are not reliable for analyses of body size shifts'.

PMID- 29662227
TI  - Whaling catch data are not reliable for analyses of body size shifts.

PMID- 29662226
TI  - A million and more trees for science.

PMID- 29662228
TI  - Cas Adaptor Proteins Coordinate Sensory Axon Fasciculation.
AB  - Development of complex neural circuits like the peripheral somatosensory system
      requires intricate mechanisms to ensure axons make proper connections. While much
      is known about ligand-receptor pairs required for dorsal root ganglion (DRG) axon
      guidance, very little is known about the cytoplasmic effectors that mediate
      cellular responses triggered by these guidance cues. Here we show that members of
      the Cas family of cytoplasmic signaling adaptors are highly phosphorylated in
      central projections of the DRG as they enter the spinal cord. Furthermore, we
      provide genetic evidence that Cas proteins regulate fasciculation of DRG sensory
      projections. These data establish an evolutionarily conserved requirement for Cas
      adaptor proteins during peripheral nervous system axon pathfinding. They also
      provide insight into the interplay between axonal fasciculation and adhesion to
      the substrate.

PMID- 29662230
TI  - Reliability and validity of the new VikingSlice software for computed tomography
      body composition analysis.
AB  - BACKGROUND/OBJECTIVES: Body composition assessment by computed tomography (CT) is
      increasingly used for diagnostic and prognostic purposes in various patient
      groups. This study aimed to compare the reliability and validity of a newly in
      house developed segmentation software VikingSlice against a commercial software
      (SliceOMatic) for quantification of adipose tissue and skeletal muscle cross
      sectional areas (CSA). SUBJECTS/METHODS: Fifty abdominal CT sets from chronic
      pancreatitis patients were analyzed (mean age 49, range 27-84 years; 38 males).
      Soft tissue CSAs at level of 4th lumbar vertebra were assessed by measuring
      standard Hounsfield unit threshold definitions with both softwares. Analysis with
      VikingSlice included automatic segmentation of interested region with subsequent
      manual corrections. Analysis with SliceOMatic included manual segmentation of
      each area. Same investigator measured CSAs using both programs. Inter-observer
      reliability of CSAs measurements with VikingSlice were assessed by comparing
      results from two independent investigators. Measurements were compared using the
      intra-class correlation coefficient (ICC), coefficient of variation (CV), Jaccard
      index and Bland-Altman analyses. RESULTS: The inter-observer reliability of
      VikingSlice was excellent (CV 3.4-15.4%, ICC 0.979-0.999, Jaccard index 0.68
      0.98). Validity was high (CV 1.6-10.2%, ICC 0.950-0.997) for measurements by
      SliceOmatic and VikingSlice. The findings were supported in the Bland-Altman
      plots. The reliability study had small average differences with means of soft
      tissue compartments in range -2.29 cm2 to 1.56 cm2; average differences between
      both softwares were -1.28 cm2 to 0.31 cm2. CONCLUSIONS: The in-house developed
      software VikingSlice was fast and showed good reliability that is comparable with
      commercial software in its utility to estimate adipose tissue and skeletal muscle
      CSAs.

PMID- 29662231
TI  - Processed meat and risk of selected digestive tract and laryngeal cancers.
AB  - BACKGROUND/OBJECTIVES: To assess the association between processed meat and the
      risk of selected digestive tract and laryngeal cancers. SUBJECTS/METHODS: We
      conducted a series of case-control studies between 1985 and 2007 in Italy. The
      studies included a total of 1475 cases of cancer of the oral cavity and pharynx,
      1077 of the larynx, 716 of the esophagus, 999 of the stomach, 684 of the liver,
      159 of the biliary tract, 688 of the pancreas, and a total of 9720 controls. Odds
      ratios (ORs), and the corresponding 95% confidence intervals (CIs), were
      estimated by unconditional logistic regression models, including terms for socio
      demographic factors, tobacco smoking, and alcohol intake. RESULTS: Compared to
      the lowest tertile of processed meat consumption, the ORs for subjects in the
      highest one were 1.18 (95% CI 0.98-1.43) for oral cavity and pharyngeal, 1.51
      (95% CI 1.18-1.91) for esophageal, 1.19 (95% CI 0.96-1.47) for laryngeal, 0.98
      (95% CI 0.81-1.18) for stomach, 0.85 (95% CI 0.51-1.40) for biliary tract, 1.20
      (95% CI 0.94-1.54) for liver, and 1.46 (95% CI 1.15-1.85) for pancreatic cancers.
      CONCLUSIONS: Our findings support the hypothesis that high processed meat
      consumption increases esophageal and pancreatic cancers risk. Residual
      confounding by socio-demographic factors, tobacco smoking, and alcohol intake
      may, partly or largely, account for these associations. We found no overall
      association with other digestive tract and laryngeal cancers.

PMID- 29662229
TI  - Modulation of Hoogsteen dynamics on DNA recognition.
AB  - In naked duplex DNA, G-C and A-T Watson-Crick base pairs exist in dynamic
      equilibrium with their Hoogsteen counterparts. Here, we used nuclear magnetic
      resonance (NMR) relaxation dispersion and molecular dynamics (MD) simulations to
      examine how Watson-Crick/Hoogsteen dynamics are modulated upon recognition of
      duplex DNA by the bisintercalator echinomycin and monointercalator actinomycin D.
      In both cases, DNA recognition results in the quenching of Hoogsteen dynamics at
      base pairs involved in intermolecular base-specific hydrogen bonds. In the case
      of echinomycin, the Hoogsteen population increased 10-fold for base pairs
      flanking the chromophore most likely due to intermolecular stacking interactions,
      whereas actinomycin D minimally affected Hoogsteen dynamics at other sites.
      Modulation of Hoogsteen dynamics at binding interfaces may be a general
      phenomenon with important implications for DNA-ligand and DNA-protein
      recognition.

PMID- 29662232
TI  - Characterization of AiiK, an AHL lactonase, from Kurthia huakui LAM0618T and its
      application in quorum quenching on Pseudomonas aeruginosa PAO1.
AB  - N-Acyl homoserine lactones (AHLs) act as the key quorum sensing (QS) signal
      molecules in gram-negative bacteria, which coordinates gene expression and then
      activates various processes, including biofilm formation and production of
      virulence factors in some pathogens. Quorum quenching (QQ), which is the
      inactivation of the signal molecules by means of enzymatic degradation or
      modification, inhibits the processes of QS rather than killing the pathogens and
      is a promising antipathogenic strategy to control the bacterial pathogens. In
      this study, an AHL lactonase gene (named aiiK) was cloned from Kurthia huakuii
      LAM0618T and the AHL lactonase AiiK was expressed by Escherichia coli. AiiK
      exhibits a variable substrate spectrum and efficient degradation of the AHL
      compounds. The enzyme assays demonstrated that AiiK behaves as an AHL lactonase
      that can hydrolyze the lactone bond of the AHLs. The total hydrolytic efficiency
      of AiiK for C10-HSL is 3.9 s-1.mM-1. AiiK can also maintain 20% activity after 12
      h incubation at 37  degrees C and demonstrate great resistance to alpha
      chymotrypsin, trypsin, and protease K. Furthermore, AiiK significantly inhibits
      the biofilm formation and attenuates extracellular proteolytic activity and
      pyocyanin production of Pseudomonas aeruginosa PAO1, which indicates the
      potential application of AiiK as a biocontrol agent or an anti-pathogenic drug.

PMID- 29662233
TI  - A murine model of atopic dermatitis can be generated by painting the dorsal skin
      with hapten twice 14 days apart.
AB  - Drug development involves pharmacometric experiments in animals. Such experiments
      should limit animal pain and stress. Conventional murine models of atopic
      dermatitis (AD) used in drug development are generated by weekly painting of
      hapten on dorsal skin for 5 weeks. The present study aimed to develop a protocol
      that involves less animal distress. The experiments focused on serum total IgE
      levels, which are a marker of AD. The conventional protocol induced ever rising
      IgE levels. Experiments with extended intervals between sensitizations showed
      that IgE peaked ~5 days after the second sensitization, after which it returned
      to the control level within 12-19 days. An additional third sensitization on day
      28 further increased the serum IgE level. In the 4-5 days after the second
      sensitization, the dorsal skin exhibited typical AD-like lesions with edema,
      scabs, epithelial-cell hypertrophy, marked mast-cell and lymphocyte infiltration
      of dermis, and increased IL-4, IL-6, IL-10, IL-1beta, IL-17A, IFN-gamma and TNF
      alpha expression. Thus, two 2,4-dinitrofluorobenzene sensitizations yield a
      murine AD model in less than 20 days. This study shows that animal model
      protocols used in drug development can be fine-tuned so that they remain
      effective yet cause animals less stress and pain.

PMID- 29662234
TI  - Modular assembly of proteins on nanoparticles.
AB  - Generally, the high diversity of protein properties necessitates the development
      of unique nanoparticle bio-conjugation methods, optimized for each different
      protein. Here we describe a universal bio-conjugation approach which makes use of
      a new recombinant fusion protein combining two distinct domains. The N-terminal
      part is Glutathione S-Transferase (GST) from Schistosoma japonicum, for which we
      identify and characterize the remarkable ability to bind gold nanoparticles
      (GNPs) by forming gold-sulfur bonds (Au-S). The C-terminal part of this multi
      domain construct is the SpyCatcher from Streptococcus pyogenes, which provides
      the ability to capture recombinant proteins encoding a SpyTag. Here we show that
      SpyCatcher can be immobilized covalently on GNPs through GST without the loss of
      its full functionality. We then show that GST-SpyCatcher activated particles are
      able to covalently bind a SpyTag modified protein by simple mixing, through the
      spontaneous formation of an unusual isopeptide bond.

PMID- 29662235
TI  - Expression of PLAGL2 in bladder urothelial carcinoma and its relationship to
      lymph node metastasis and survival.
AB  - The purpose of this study was to investigate PLAGL2 expression associated with
      pathological features and prognosis and predicted lymph node metastases in the
      bladder urothelial carcinoma (BUC) tissue. The pathologic specimens and clinical
      data of 203 patients with bladder urothelial carcinoma after radical resection
      were collected. The expression of PLAGL2 was detected by immunohistochemically
      staining. The influence on lymph node metastasis and the prognoses of BUC
      patients were analyzed. The expression of PLAGL2 in BUC and positive lymph nodes
      was significantly higher than the normal bladder tissues (89.06% and 76.56% vs
      21.88%, P < 0.001). Logistic regression analysis showed that PLAGL2 expression
      was an independent risk factor for BUC lymph node metastasis (P < 0.05). COX
      proportional hazards regression model showed that the time to recurrence and
      overall survival of patients with overexpression of PLAGL2 were significantly
      lower than those with low expression (P < 0.05). PLAGL2 is highly expressed in
      the BUC tissue and metastatic lymph node relative to the normal bladder tissue.
      This expression correlates to tumor size and number, and tumor grade and stage.
      Overexpression of PLAGL2 can be an independent predictor for lymph node
      metastasis and patient survival.

PMID- 29662236
TI  - Author Correction: disLocate: tools to rapidly quantify local intermolecular
      structure to assess two-dimensional order in self-assembled systems.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 29662237
TI  - Take a left here.

PMID- 29662238
TI  - Structural underpinnings of oestrogen receptor mutations in endocrine therapy
      resistance.
AB  - Oestrogen receptor-alpha (ERalpha), a key driver of breast cancer, normally
      requires oestrogen for activation. Mutations that constitutively activate ERalpha
      without the need for hormone binding are frequently found in endocrine-therapy
      resistant breast cancer metastases and are associated with poor patient outcomes.
      The location of these mutations in the ER ligand-binding domain and their impact
      on receptor conformation suggest that they subvert distinct mechanisms that
      normally maintain the low basal state of wild-type ERalpha in the absence of
      hormone. Such mutations provide opportunities to probe fundamental issues
      underlying ligand-mediated control of ERalpha activity. Instructive contrasts
      between these ERalpha mutations and those that arise in the androgen receptor
      (AR) during anti-androgen treatment of prostate cancer highlight differences in
      how activation functions in ERs and AR control receptor activity, how hormonal
      pressures (deprivation versus antagonism) drive the selection of phenotypically
      different mutants, how altered protein conformations can reduce antagonist
      potency and how altered ligand-receptor contacts can invert the response that a
      receptor has to an agonist ligand versus an antagonist ligand. A deeper
      understanding of how ligand regulation of receptor conformation is linked to
      receptor function offers a conceptual framework for developing new anti
      oestrogens that might be more effective in preventing and treating breast cancer.

PMID- 29662239
TI  - Elimination of TDP-43 inclusions linked to amyotrophic lateral sclerosis by a
      misfolding-specific intrabody with dual proteolytic signals.
AB  - Aggregation of TAR DNA-binding protein of 43 kDa (TDP-43) is implicated in the
      pathogenesis of sporadic and certain familial forms of amyotrophic lateral
      sclerosis (ALS), suggesting elimination of TDP-43 aggregates as a possible
      therapeutic strategy. Here we generated and investigated a single-chain variable
      fragment (scFv) derived from the 3B12A monoclonal antibody (MAb) that recognises
      D247 of the TDP-43 nuclear export signal, an epitope masked in the physiological
      state. In transfected HEK293A cells, 3B12A scFv recapitulated the affinity of the
      full-length MAb to mislocalised TDP-43 with a defective nuclear localising signal
      and to a TDP-43 inclusion mimic with cysteine-to-serine substitution at RRM1.
      Moreover, 3B12A scFv accelerated proteasome-mediated degradation of aggregated
      TDP-43, likely due to an endogenous PEST-like proteolytic signal sequence in the
      VH domain CDR2 region. Addition of the chaperone-mediated autophagy (CMA)-related
      signal to 3B12A scFv induced HSP70 transcription, further enhancing TDP-43
      aggregate clearance and cell viability. The 3B12A scFv also reduced TDP-43
      aggregates in embryonic mouse brain following in utero electroporation while
      causing no overt postnatal brain pathology or developmental anomalies. These
      results suggest that a misfolding-specific intrabody prone to synergistic
      proteolysis by proteasomal and autophagic pathways is a promising strategy for
      mitigation of TDP-43 proteinopathy in ALS.

PMID- 29662240
TI  - Microcrack healing in non-ferrous metal tubes through eddy current pulse
      treatment.
AB  - This study proposed a novel method to heal microcrack within Mg alloy tubes using
      high density eddy current pulse treatment (ECPT). Through electromagnetic
      induction inside a copper coil connected with a high density pulse power source
      supply, the high density (greater than 5 * 109 A/m2) and short duration eddy
      current was generated in tube specimens of Mg alloy. The results show that the
      microcracks in tube specimens was healed evidently and the mechanical properties
      of the tubes subjected to ECPT were improved simultaneously. The crack healing
      during ECPT was ascribed to not only the thermal stress around the microcrack
      tips and the softening or melting of metals in the vicinity of microcrack tips,
      but also the squeezing action acted by the Lorentz force. In the inward
      discharging scheme, both the compressive radial stress and tangential stress
      induced by the Lorentz force contributed to more sufficient crack healing and
      thus better mechanical properties of tube specimens after the ECPT experiment,
      compared to the outward-discharging scheme. The ECPT can heal microcracks
      automatically without directly contacting tubular specimens and is not limited by
      the length of tubular workpieces, exhibiting great potential for crack healing in
      non-ferrous alloy tubes.

PMID- 29662241
TI  - Low Mother-to-Child CCL22 Chemokine Levels Are Inversely Related to Mite
      Sensitization and Asthma in Early Childhood.
AB  - Few studies have addressed the mother-to-child transmission of Th2 immunity and
      the impact on the development of atopic diseases in early childhood. We
      investigated 186 children who were followed-up regularly for 4 years in a birth
      cohort study. The levels of Th2 related chemokine (C-C motif) ligand 17 (CCL17)
      and CCL22 were quantified in cord blood and at 1.5 years-of-age using multiplex
      Luminex kits. The levels of 125 pairs of CCL17 and CCL22 chemokines from birth to
      1.5 years were recorded in this study. Using K-means clustering, only the
      declining trend of CCL22 levels was separately clustered (cluster A, n = 51;
      cluster B, n = 46; cluster C, n = 28). Mothers of children with higher CCL22
      chemokine levels at birth were significantly more likely to display
      Dermatophagoides pteronyssinus sensitization. A lower CCL22 level at birth with a
      slight rise during infancy was associated with higher prevalence of mite
      sensitization and a higher risk of asthma at 3 years-of-age (P = 0.014). In
      conclusion, low mother-to-child Th2-associated chemokine CCL22 levels appear to
      be inversely related to mite sensitization and the risk of asthma development in
      early childhood.

PMID- 29662242
TI  - Reorganization takes energy.

PMID- 29662243
TI  - Reorganization energy upon charging a single molecule on an insulator measured by
      atomic force microscopy.
AB  - Intermolecular single-electron transfer on electrically insulating films is a key
      process in molecular electronics1-4 and an important example of a redox
      reaction5,6. Electron-transfer rates in molecular systems depend on a few
      fundamental parameters, such as interadsorbate distance, temperature and, in
      particular, the Marcus reorganization energy 7 . This crucial parameter is the
      energy gain that results from the distortion of the equilibrium nuclear geometry
      in the molecule and its environment on charging8,9. The substrate, especially
      ionic films 10 , can have an important influence on the reorganization
      energy11,12. Reorganization energies are measured in electrochemistry 13 as well
      as with optical14,15 and photoemission spectroscopies16,17, but not at the single
      molecule limit and nor on insulating surfaces. Atomic force microscopy (AFM),
      with single-charge sensitivity18-22, atomic-scale spatial resolution 20 and
      operable on insulating films, overcomes these challenges. Here, we investigate
      redox reactions of single naphthalocyanine (NPc) molecules on multilayered NaCl
      films. Employing the atomic force microscope as an ultralow current meter allows
      us to measure the differential conductance related to transitions between two
      charge states in both directions. Thereby, the reorganization energy of NPc on
      NaCl is determined as (0.8 +/- 0.2) eV, and density functional theory (DFT)
      calculations provide the atomistic picture of the nuclear relaxations on
      charging. Our approach presents a route to perform tunnelling spectroscopy of
      single adsorbates on insulating substrates and provides insight into single
      electron intermolecular transport.

PMID- 29662244
TI  - Refined graft-versus-host disease/relapse-free survival in transplant from HLA
      identical related or unrelated donors in acute myeloid leukemia.
AB  - Refined graft-versus-host disease (GVHD)/relapse-free survival (GRFS) considers
      main outcomes of allogeneic stem cell transplant (HSCT), estimating long-term
      survival without significant morbidity as a surrogate of HSCT success. We
      compared GRFS in 5059 adults with acute myeloid leukemia (AML), undergoing HSCT
      in first complete remission from 2000 to 2015 either from a matched sibling (MSD,
      n = 3731) or unrelated donor (MUD, n = 1328). Median age was 49 (range: 18-76)
      years. Median follow-up was 32 and 60 months in MSD and MUD, respectively (p <
      0.01). Compared to MSD, at 4 years, MUD recipients had lower GRFS, with higher
      NRM, grade III-IV acute GVHD, and extensive chronic GVHD (HR: 1.42, p < 0.01). We
      also performed a risk factor analyses, showing unfavorable cytogenetics (HR:
      1.42, p < 0.01) and peripheral blood as stem cell source (HR: 1.22, p < 0.01)
      associated to lower GRFS, while this was higher with in vivo T-cell depletion
      (TCD, HR: 0.73, p < 0.01) and shorter time from diagnosis to HSCT (HR 0.96, p <
      0.01). Different factors, modifiable or not, such as donor type, stem cell
      source, disease biology, and in vivo TCD, impact on GRFS and this may guide in
      the future transplant choices to improve morbidity and long-term quality of life.

PMID- 29662245
TI  - Early human cytomegalovirus reactivation is associated with lower incidence of
      relapse of myeloproliferative disorders after allogeneic hematopoietic stem cell
      transplantation.
AB  - Conflicting results have been reported regarding the association between early
      cytomegalovirus (CMV) reactivation and relapse after allogeneic hematopoietic
      stem cell transplantation (allo-HSCT). This prompted us to evaluate the impact of
      CMV reactivation on outcomes of 155 consecutive adult patients transplanted in
      our institution. In our study, CMV reactivation did not affect cumulative
      incidence (CI) of relapse in patients with lymphoproliferative disorders.
      However, the CI of relapse in patients with myeloproliferative disorders (AML and
      MPN) was 37% (95% CI, 21-53) in patients without CMV reactivation as opposed to
      17% (95% CI, 9-28) in patients with CMV reactivation (p = 0.03). An important
      correlation between CMV reactivation and relapse was found in patients with MPN;
      the CI of relapse was 50% (95% CI, 12-80) in patients without CMV reactivation as
      opposed to only 7% (95% CI, 0-27) in patients with CMV reactivation (p = 0.02). A
      substantial reduction of relapse in myeloproliferative disorders associated with
      CMV reactivation was confirmed by multivariate analysis (HR 2.73; 95% CI, 1.09
      6.82, p = 0.03) using time-dependent covariates for high-risk disease, older age,
      RIC conditioning, ATG, grade II-IV acute, and chronic GVHD. To our knowledge, we
      are the first to show an association of CMV reactivation with relapse reduction
      in MPN patients. This putative virus vs myeloproliferation effect warrants
      further research.

PMID- 29662246
TI  - Why come back home? Breeding-site fidelity varies with group size and parasite
      load in a colonial bird.
AB  - Fidelity to a past breeding site is widespread among animals and may confer both
      costs and benefits. Colonial species occur at specific sites that can accommodate
      multiple breeders, and the choice of whether to return to last year's site or
      disperse elsewhere can affect colony site use, the colony size distribution and
      individual fitness. For the colonial cliff swallow, Petrochelidon pyrrhonota,
      which occupies colonies of widely different sizes, we used a 30-year field study
      in western Nebraska to investigate how the extent of infestation by ectoparasites
      and colony size affected breeders' colony site fidelity between years. We
      compared philopatry at colonies where parasitic swallow bugs, Oeciacus vicarius,
      had been removed by fumigation with that at nonfumigated sites exposed to natural
      levels of ectoparasites. About 25% of birds at nonfumigated colonies returned to
      their previous year's site, whereas about 69% of birds at fumigated colonies did
      so. Site fidelity was greatest at nonfumigated sites that changed the least in
      size between years. Birds were less likely to return to a nonfumigated site as
      the colony there became increasingly larger. Individuals philopatric to both
      nonfumigated and fumigated sites resided in colonies more similar in size between
      years than did dispersing birds. Most cliff swallows settled within 6 km of their
      previous year's site, indicating that many nonphilopatric birds still may have
      had some familiarity with the local landscape surrounding the site to which they
      moved. Removal of ectoparasites at a site allows large colonies to persist there
      perennially, probably contributing to higher philopatry because such large
      colonies are rare and would have been difficult to find had the residents
      dispersed. Cliff swallows are likely to be sensitive to both colony size and
      general familiarity with a given site or landscape region, and probably integrate
      these with other cues to select breeding colonies.

PMID- 29662247
TI  - The Nitrogen Balancing Act: Tracking the Environmental Performance of Food
      Production.
AB  - Farmers, food supply-chain entities, and policymakers need a simple but robust
      indicator to demonstrate progress toward reducing nitrogen pollution associated
      with food production. We show that nitrogen balance-the difference between
      nitrogen inputs and nitrogen outputs in an agricultural production system-is a
      robust measure of nitrogen losses that is simple to calculate, easily understood,
      and based on readily available farm data. Nitrogen balance provides farmers with
      a means of demonstrating to an increasingly concerned public that they are
      succeeding in reducing nitrogen losses while also improving the overall
      sustainability of their farming operation. Likewise, supply-chain companies and
      policymakers can use nitrogen balance to track progress toward sustainability
      goals. We describe the value of nitrogen balance in translating environmental
      targets into actionable goals for farmers and illustrate the potential roles of
      science, policy, and agricultural support networks in helping farmers achieve
      them.

PMID- 29662249
TI  - Managing for Multifunctionality in Perennial Grain Crops.
AB  - Plant breeders are increasing yields and improving agronomic traits in several
      perennial grain crops, the first of which is now being incorporated into
      commercial food products. Integration strategies and management guidelines are
      needed to optimize production of these new crops, which differ substantially from
      both annual grain crops and perennial forages. To offset relatively low grain
      yields, perennial grain cropping systems should be multifunctional. Growing
      perennial grains for several years to regenerate soil health before rotating to
      annual crops and growing perennial grains on sloped land and ecologically
      sensitive areas to reduce soil erosion and nutrient losses are two strategies
      that can provide ecosystem services and support multifunctionality. Several
      perennial cereals can be used to produce both grain and forage, and these dual
      purpose crops can be intercropped with legumes for additional benefits. Highly
      diverse perennial grain polycultures can further enhance ecosystem services, but
      increased management complexity might limit their adoption.

PMID- 29662248
TI  - Internet Blogs, Polar Bears, and Climate-Change Denial by Proxy.
AB  - Increasing surface temperatures, Arctic sea-ice loss, and other evidence of
      anthropogenic global warming (AGW) are acknowledged by every major scientific
      organization in the world. However, there is a wide gap between this broad
      scientific consensus and public opinion. Internet blogs have strongly contributed
      to this consensus gap by fomenting misunderstandings of AGW causes and
      consequences. Polar bears (Ursus maritimus) have become a "poster species" for
      AGW, making them a target of those denying AGW evidence. Here, focusing on Arctic
      sea ice and polar bears, we show that blogs that deny or downplay AGW disregard
      the overwhelming scientific evidence of Arctic sea-ice loss and polar bear
      vulnerability. By denying the impacts of AGW on polar bears, bloggers aim to cast
      doubt on other established ecological consequences of AGW, aggravating the
      consensus gap. To counter misinformation and reduce this gap, scientists should
      directly engage the public in the media and blogosphere.

PMID- 29662250
TI  - Personal Conflict Impairs Performance on an Unrelated Self-Control Task:
      Lingering Costs of Uncertainty and Conflict.
AB  - People have the ability to make important choices in their lives, but
      deliberating about these choices can have costs. The present study was designed
      to test the hypothesis that writing about conflicted personal goals and values
      (conflict condition) would impair self-control on an unrelated subsequent task as
      compared to writing about clear personal goals and values (clarity condition).
      Personal conflict activates the behavioral inhibition system (BIS; Hirsh, Mar, &
      Peterson, 2012), which may make it harder for participants to successfully
      execute self-control. In this large (N=337), pre-registered study participants in
      the conflict condition performed worse on anagrams than participants in the
      clarity condition, and the effect of condition on anagram performance was
      mediated by a subjective uncertainty measure of BIS activation. This suggests
      that BIS activation leads to poor self-control. Moreover, given that conflict is
      inherent in the exercise of self-control, results point to BIS activation as a
      mechanism for why initial acts of self-control impair self-control on subsequent,
      unrelated tasks.

PMID- 29662251
TI  - Motherhood and Employment Among Whites, Hispanics, and Blacks: A Life Course
      Approach.
AB  - Research has shown that having children reduces women's employment; yet, how this
      effect differs for racial minorities has received less attention. Using random
      effects models and data from the National Longitudinal Survey of Youth (N =
      4,526), this study investigates the association between motherhood and employment
      among Whites, Hispanics, and Blacks over women's entire reproductive span.
      Results indicate that having children reduces labor force participation primarily
      by deterring full-time employment. This effect is stronger and lasts longer among
      Whites, smaller and shorter among Hispanics, and brief among Blacks. Motherhood
      reduces part-time employment for young mothers, but temporarily increases it for
      older mothers. Early childbearing partly explains Black and Hispanic women's low
      employment rates at young ages; interestingly, the evidence indicates that their
      employment prospects would benefit the most from delaying childbearing. This
      study highlights the relevance of intersectionality and the life course
      perspective for investigating inequality in the labor market.

PMID- 29662252
TI  - Scalable Synthesis of Hydrido-Disiloxanes from Silanes: A One-Pot Preparation of
      1,3-Diphenyldisiloxane from Phenylsilane.
AB  - A simple, one-pot, and high-yielding synthesis of 1,3-diphenyldisiloxane is
      presented. The preparation of similar symmetrical disiloxane materials is also
      accomplished with this same protocol. This mechano-chemical procedure is
      efficient and highly scalable, furnishing a convenient route to hydrido
      disiloxanes from widely accessible commercially available silanes.

PMID- 29662253
TI  - The Gas-absorption/Chemical-reaction Method for Measuring Air-water Interfacial
      Area in Natural Porous Media.
AB  - The gas-absorption/chemical-reaction (GACR) method used in Chemical Engineering
      to quantify gas-liquid interfacial area in reactor systems is adapted for the
      first time to measure the effective air-water interfacial area of natural porous
      media. Experiments were conducted with the GACR method, and two standard methods
      (x-ray microtomographic imaging and interfacial partitioning tracer tests) for
      comparison, using model glass beads and a natural sand. The results of a series
      of experiments conducted under identical conditions demonstrated that the GACR
      method exhibited excellent repeatability for maintaining constant water
      saturation and for measurement of interfacial area (Aia). Coefficients of
      variation for Aia were 3.5% for the glass beads and 11% for the sand. Estimated
      maximum interfacial areas (Am) obtained with the GACR method were statistically
      identical to independent measures of the specific solid surface areas of the
      media. For example, the Am for the glass beads is 29 (+/-1) cm-1, compared to 32
      (+/-3), 30 (+/-2), and 31 (+/-2) cm-1 determined from geometric calculation,
      N2/BET measurement, and microtomographic measurement, respectively. This
      indicates that the method produced accurate measures of interfacial area.
      Interfacial areas determined with the GACR method were similar to those obtained
      with the standard methods. For example, Aias of 47 and 44 cm-1 were measured with
      the GACR and XMT methods, respectively, for the sand at a water saturation of
      0.57. The results of the study indicate that the GACR method is a viable
      alternative for measuring air-water interfacial areas. The method is relatively
      quick, inexpensive, and requires no specialized instrumentation compared to the
      standard methods.

PMID- 29662254
TI  - Cooperative Decision-Making and Intimate Partner Violence in Peru.
AB  - Using the continuous Demographic and Health Surveys (2005-2012) for Peru, we
      employ multinomial logistic regression estimates to assess risk for intimate
      partner violence (IPV). Using empowerment and gender frameworks for IPV, we find
      that women making more household decisions jointly are less likely to experience
      physical violence. We also find that education is negatively associated with IPV,
      unless a woman's attainment exceeds her partner's. Although women earning more
      than their partners are more likely to experience violence, joint decision-makers
      have a lower risk of moderate physical violence even when their status exceeds
      that of a male partner. By adding measures for relationship dynamics, we
      highlight the ways decision-making within the household contributes to violence
      risk for women. While deviating from male-breadwinning norms can result in
      violence, risk factors are conditioned on the nature of cooperation within a
      partnership. Our findings suggest that shared power within the household reduces
      IPV risk.

PMID- 29662255
TI  - The uncertainty of colombian scientific journals with Publindex.

PMID- 29662256
TI  - Analysis of combat casualties admitted to the emergency department during the
      negotiation of the comprehensive Colombian process of peace.
AB  - Aim: Our objective was to describe the variations in casualties admitted to the
      emergency department during the period of the negotiation of the comprehensive
      peace agreement in Colombia between 2011 and 2016. Methods: A retrospective study
      of all hostile military casualties managed at a regional Level I trauma center
      from January 2011 to December 2016. Patients were subsequently divided into two
      groups: those seen before the declaration of the process of peace truce (November
      2012) and those after (negotiation period). Variables were compared with respect
      to periods. Results: A total of 448 hostile casualties were registered. There was
      a gradual decline in the number of admissions to the emergency department during
      the negotiation period. The number of soldiers suffering blast and rifle injuries
      also decreased over this period. In 2012 there were nearly 150 hostile
      casualties' admissions to the ER. This number decreased to 84, 63, 32 and 6 in
      2013, 2014, 2015 and 2016 respectively. Both, the proportion of patients with an
      ISS >=9 and admitted to the intensive care unit were significantly higher in the
      period before peace negotiation. From August to December/2016 no admissions of
      war casualties were registered. Conclusion: We describe a series of soldiers
      wounded in combat that were admitted to the emergency department before and
      during the negotiation of the Colombian process of peace. Overall, we found a
      trend toward a decrease in the number of casualties admitted to the emergency
      department possibly in part, as a result of the period of peace negotiation.

PMID- 29662257
TI  - 17-hydroxiprogesterone values in healthy preterm infants.
AB  - Introduction: In preterm newborn, problems with the interpretation of 17-OHP may
      occur. Objective: Evaluate 17-OHP values in healthy preterm newborns until they
      reach the corrected gestational age. Methods: Longitudinal study of 36 preterm
      infants with 17-OHP evaluation using ELISA from heel blood from 3 to 5 days and
      thereafter every 2 weeks until the corrected gestational age. Values adjusting
      multiple variables such as gestational age, birth weight and sex, among others
      were compared. The results were analyzed against 82 healthy full-term infants.
      Results: In the first week of life, early term infants born within less than 34
      months of gestational age show 17-OHP values that are much higher than the full
      term neonates. After a week, the values decrease and stabilize, but are still
      higher than those of full term neonates and remain so even at the corrected
      gestational age. (average difference of 63.0%, CI 95%: 11.8%-115.5%). 33.6% (41
      samples) of a total of 122 samples taken from preterm infants were higher than 30
      ng/mL. Conclusions: 17-OHP values in early term infants are higher than those in
      full term neonates and can be related to postnatal adaptive processes. It is
      suggested that a second screening at the 37th week of corrected age be performed.

PMID- 29662258
TI  - Frequency of common polymorphisms in Caveolin 1 ( CAV1 ) gene in adults with high
      serum triglycerides from Colombian Caribbean Coast.
AB  - Background: Caveolin 1 gene (CAV1) has been associated with insulin resistance,
      metabolic syndrome and hypertension in humans. Also, it has been related to high
      serum triglycerides in rodents, however there is little evidence of this relation
      in humans. Aim: To describe frequencies of common variations in CAV1 in adults
      with high serum triglycerides. Methods: A case-control study was carried out with
      adults from Colombian Caribbean Coast. A whole blood sample was employed to
      measure serum concentrations of triglycerides, glucose, total cholesterol and
      HDLc. Six common Single Nucleotide Polymorphism (SNP) in CAV1 were genotyped
      (rs926198, rs3779512, rs10270569, rs11773845, rs7804372 and rs1049337). Allelic
      and genotypic frequencies were determined by direct count and Hardy-Weinberg
      Equilibrium (HWE) was assessed. Case and control groups were compared with null
      hypothesis tests. Results: A total of 220 cases and 220 controls were included.
      For rs3779512 an excess in homozygotes frequency was found within case group
      (40.4% (GG), 41.3% (GT) and 18.1% (TT); Fis=0.13, p=0.03). Another homozygotes
      excess among case group was found in rs7804372 (59.5% (TT), 32.3% (TA) and 8.2%
      (AA); Fis= 0.12, p= 0.04). In rs1049337, cases also showed an excess in
      homozygotes frequency (52.7% (CC), 35.0% (CT) and 12.3% (TT); Fis= 0.16, p=
      0.01). Finally, for rs1049337 there were differences in genotype distribution
      between case and control groups (p <0.05). Conclusion: An increased frequency of
      homozygote genotypes was found in subjects with high serum triglycerides. These
      findings suggest that minor alleles for SNPs rs3779512, rs7804372 and rs1049337
      might be associated to higher risk of hypertriglyceridemia.

PMID- 29662259
TI  - Psychometric validation of the Columbia-Suicide Severity rating scale in Spanish
      speaking adolescents.
AB  - Introduction: Adolescent suicide is a major public health issue, and early and
      accurate detection is of great concern. There are many reliable instruments for
      this purpose, such as the Columbia-Suicide severity rating scale (C-SSRS), but no
      validation exists for Spanish speaking Latin American adolescents. Objetive: To
      assess psychometric properties and cut-off scores of the C-SSRS in Spanish
      speaking adolescents. Methods: Exploratory assessment with principal component
      analysis (PCA) and Varimax rotation, and confirmatory analysis (CFA) were
      performed on two groups with 782 and 834 participants respectively (N=1616). Mean
      age was 24.8 years. A Receiver operator analysis was applied to distinguish
      between control and suicide-risk subgroups adolescents. Results: Promax rotation
      yielded two 10-items factors, for suicide ideation and behavior respectively. C
      SSRS was positively correlated with other suicide risk scales, such as Beck
      Depression Inventory-II, Suicidal Behaviors Questionnaire-Revised, or PHQ-9.
      Confirmatory factor analysis yielded a two-factor solution as the best goodness
      of fit model. C-SSRS showed adequate ability to detect suicide risk group with
      positive predictive value of 68.3%. ROC analyses showed cutoff scores of >= 6 and
      >= 4 for suicide ideation and behavior scales respectively. Conclusion: This
      research offers data supporting psychometric validity and reliability of C-SSRS
      in nonclinical Spanish-speaking students. Added benefits are flexible scoring and
      management easiness. This questionnaire yields data on distinct aspects of
      suicidality, being more parsimonious than separate administration of a bunch of
      questionnaires.

PMID- 29662260
TI  - Characterization of multidrug-resistant Acinetobacter ssp. strains isolated from
      medical intensive care units in Cali - Colombia.
AB  - Introduction: The extensive use of antibiotics has led to the emergence of multi
      resistant strains in some species of the genus Acinetobacter. Objective: To
      investigate the molecular characteristics of multidrug-resistant of Acinetobacter
      ssp. strains isolated from 52 patients collected between March 2009 and July 2010
      in medical intensive care units in Cali - Colombia. Methods: The susceptibility
      to various classes of antibiotics was determined by disc diffusion method, and
      the determination of the genomic species was carried out using amplified
      ribosomal DNA restriction analysis (ARDRA) and by sequencing of the 16s rDNA
      gene. Also, the genes of beta-lactamases as well as, integrases IntI1 and IntI2
      were analyzed by PCR method. Results: The phenotypic identification showed that
      the isolates belong mainly to A. calcoaceticus- A. baumannii complex. All of them
      were multi-resistant to almost the whole antibiotics except to tigecycline and
      sulperazon, and they were grouped into five (I to V) different antibiotypes,
      being the antibiotype I the most common (50.0%). The percent of beta-lactamases
      detected was: blaTEM (17.3%), blaCTX-M (9.6%), blaVIM (21.2%), blaIMP (7.7%),
      blaOXA-58 (21.2%), and blaOXA-51 (21.2%). The phylogenetic tree analysis showed
      that the isolates were clustering to A. baumannii (74.1%), A. nosocomialis
      (11.1%) and A. calcoaceticus (7.4 %). Besides, the integron class 1 and class 2
      were detected in 23.1% and 17.3% respectively. Conclusion: The isolates were
      identified to species A. baumanii mainly, and they were multiresistant. The
      resistance to beta-lactams may be by for presence of beta-lactamases in the
      majority of the isolates.

PMID- 29662262
TI  - Treatment of endo-periodontal lesion using leukocyte-platelet-rich fibrin. A case
      report.
AB  - Case Description: The main objective of this paper was to report the clinical
      effectiveness of leukocyte- platelet- rich fibrin (L-PRF) in the treatment of a
      combined endo-periodontal lesion of an upper first premolar. Clinical Findings:
      The tooth had a profound abfraction on the vestibular aspect and presented no
      mobility but revealed a deep pocket measuring of 11 mm on the mesial vestibular
      aspect and 14 mm on the mesial palatine aspect. The three dimensional image
      analysis showed total bone loss in the mesial aspect and an extensively bone loss
      of the vestibular aspect of the vestibular root. Treatment and Outcome:
      Endodontic treatment was performed and periodontal access surgery (surgical
      periodontal therapy) was done with the application of autologous L-PRF. Three
      month and 6 months after surgery, the cone beam computed tomography (CBCT) exams
      showed no bone regeneration in any aspect of the tooth. However, periodontal
      examination showed a significative improvement in the deepness of surcus. The
      mesial vestibular aspect had a deep pocket of 3 mm and 5 mm on the mesial
      palatine aspect showing a reduction in deepness of 8 mm and 9 mm, respectively.
      Clinical Relevance: The actual treatment for teeth with bad prognosis is the
      extraction and replacement with implants. Even though implants are capable of
      restore function and aesthetic, the abuse of this approach have led to the loss
      of teeth that could be successfully treated with a less invasive technique. The
      prognosis of teeth with endoperiodontal lesion is poor but could be enhanced with
      regenerative therapies. Until now there are no clinical trials and just four case
      report about the treatment of these teeth with platelet rich fibrin.

PMID- 29662261
TI  - Prediabetes in Colombia: Expert Consensus.
AB  - The prevalence of Prediabetes in Colombia is high, and despite being recognized
      and categorized in the main Medical Guidelines and included in the International
      Classification of Diseases in Colombia, knowledge and awareness of it is limited
      amongst healthcare professionals and in the community. Our expert group
      recommends that educational programs emphasize a global approach to risk which
      includes a recognition of the importance of prediabetes and its evaluation along
      with and other risk factors such as a family history of DM2, overweight and
      obesity, dislipidemia and hypertension. Studies conducted in Colombia demonstrate
      the value of the FINDRIS questionnaire as a tool to identify subjects at risk of
      prediabetes and DM2, and we recommend that it should be systematic applied
      throughout the country as part of government policy. Prediabetes progresses to
      DM2 at an annual rate of 10%, but it has also been shown that prediabetes is an
      independent risk factor for cardiovascular outcomes. On this basis, the Committee
      recommends that once prediabetes is detected and diagnosed, immediate management
      of the disease begins through lifestyle changes, with follow up assessments
      performed at 3 and 6 months. If the patient does not respond with a weight loss
      of at least 5% and if the HbA1C values are not normalized, pharmacological
      management should be initiated with a metformin dose of 500 mg / day, increasing
      up to 1,500 - 1,700 mg / day, according to tolerance.

PMID- 29662263
TI  - Online updating method with new variables for big data streams.
AB  - For big data arriving in streams, online updating is an important statistical
      method that breaks the storage barrier and the computational barrier under
      certain circumstances. In the regression context, online updating algorithms
      assume that the set of predictor variables does not change, and consequently
      cannot incorporate new variables that may become available midway through the
      data stream. A naive approach would be to discard all previous information and
      start updating with new variables from scratch. We propose a method that utilizes
      the information from earlier data in the online updating algorithm with bias
      corrections to improve efficiency. The method is developed for linear models
      first, and then extended to estimating equations for generalized linear models.
      Closed-form expressions for the efficiency gain over the naive approach are
      derived in a particular linear model setting. We compare the performance of our
      proposed bias-correcting approach and the naive approach in simulation studies
      with data generated from a normal linear model and a logistic regression model.
      The method is applied to a study on airline delay, where reasons for delays were
      only available more recently, starting in 2003.

PMID- 29662264
TI  - Chromosome 6q24-related diabetes mellitus.
AB  - Chromosome 6q24-related diabetes mellitus is the most common cause of transient
      neonatal diabetes (TNDM), accounting for approximately two-thirds of all TNDM
      cases. Patients with 6q24-TNDM develop insulin-requiring diabetes soon after
      birth, followed by the gradual improvement and eventual remission of the disorder
      by 18 mo of age. The most important clinical feature of affected patients is a
      small-for-gestational age (SGA) birth weight, which reflects the lack of insulin
      in utero. It is believed that 6q24-TNDM is caused by the overexpression of the
      paternal allele of the imprinted locus in chromosome 6q24, which contains only
      two expressed genes, PLAGL1 and HYMAI. Identified mechanisms include: (1)
      duplication of the paternal allele, (2) paternal uniparental disomy, and (3)
      hypomethylation of the maternal allele. Many patients with TNDM relapse after
      puberty. Relapsed 6q24-related diabetes is no longer transient and typically
      occurs in non-obese patients who are autoantibody negative. Thus, these patients
      possess features indistinguishable from those of maturity-onset diabetes of the
      young (MODY). Conversely, it has been shown that not all patients with 6q24
      related diabetes have a history of TNDM. 6q24-related diabetes should therefore
      be considered as one of the differential diagnoses for patients with MODY-like
      diabetes, especially when they are SGA at birth.

PMID- 29662265
TI  - Thyroid hormone status in patients with severe selenium deficiency.
AB  - Selenium (Se) is an essential trace element that is involved in numerous
      biological processes in the form of a selenoprotein such as iodothyronine
      deiodinase (DIO). Se deficiency may prevent the conversion of T4 to T3 through
      reducing DIO expression and thereby affecting thyroid hormone status. However,
      this has not been well documented in humans. In this study, to clarify the
      association between Se and thyroid hormone status, we investigated the thyroid
      hormone levels in patients with severe Se deficiency (< 2 ug/dl). Severe Se
      deficiency was associated with increases in free T4 levels, but not with
      decreases and increases in free T3 and thyroid stimulating hormone (TSH) levels,
      respectively. Increases in free T4 levels during Se deficiency were reduced with
      Se supplementation; however, neither free T3 nor TSH levels were affected. Taken
      together, these findings indicate that free T4 may be a useful biomarker for Se
      status when serum Se levels are severely low.

PMID- 29662266
TI  - Thyroid nodules and long-term follow-up among childhood cancer survivors who
      underwent hematopoietic stem cell transplantation.
AB  - Thyroid nodules have been observed in childhood cancer survivors (CCS) treated
      with chemotherapy and radiotherapy. We report four patients with thyroid nodules
      identified during the long-term follow-up of children who underwent hematopoietic
      stem cell transplantation (HSCT). The thyroid nodules were diagnosed as
      adenomatous goiter in all four patients. The interval between the primary cancer
      diagnosis and the occurrence of the thyroid nodules was more than 10 yr.
      Furthermore, all four patients underwent HSCT in conditioning with total body
      irradiation (TBI) before the age of 10 yr. Two of four patients commenced
      treatment with levothyroxine due to elevated TSH levels. Only two patients showed
      elevated thyroglobulin levels (> 70 ug/L). In conclusion, we suggest that CCS who
      have undergone HSCT in conditioning with TBI more than 10 yr previously should be
      followed up carefully for thyroid nodules using ultrasound.

PMID- 29662267
TI  - Decrement in bone mineral density after parathyroidectomy in a pediatric patient
      with primary hyperparathyroidism.
AB  - Primary hyperparathyroidism (PHT) causes increased bone turnover, leading to
      reduction in bone mineral density (BMD). Parathyroidectomy is a definitive
      therapy and improves BMD in adult patients with PHT. However, there are no
      reports regarding alterations of BMD in pediatric or adolescent patients with
      PHT. Here, we report a case of a 13-yr-old boy with PHT who was referred to our
      institution for evaluation of hypercalcemia and hyperparathyroidism. Radiological
      investigation revealed an ectopic parathyroid adenoma below the right thyroid
      lobe. A minimally invasive radio-guided parathyroidectomy was successfully
      performed. We followed up the patient's BMD for three years both before and after
      parathyroidectomy. Over the course of three years, his BMD was steadily
      decreased, with z-scores of +0.506 at 13 yr and 9 mo, +0.162 at 14 yr and 9 mo,
      and -0.411 at 15 yr and 9 mo. BMD usually increases during peak height velocity
      in an adolescent and improves after parathyroidectomy in adult patients with PHT.
      However, our patient showed decreased BMD z-scores following parathyroidectomy.
      Therefore, the patient had an increased risk of fracture after parathyroidectomy
      and was followed up closely. Both height and BMD should be carefully evaluated
      after parathyroidectomy in pediatric and adolescent patients with PHT.

PMID- 29662268
TI  - A pediatric case of pheochromocytoma without apparent hypertension associated
      with von Hippel-Lindau disease.
AB  - Pheochromocytomas are catecholamine-secreting tumors. These tumors are rare in
      children, and they may be associated with hereditary syndromes such as von Hippel
      Lindau (VHL) disease. Most pediatric patients with pheochromocytoma present with
      sustained hypertension, while 10% to 69% of adult patients are asymptomatic.
      Herein, we present the case of a 12-yr-old Japanese girl with pheochromocytoma
      due to a germline mutation in the VHL (Arg161Gln). The only complaint was loss of
      weight. Pyrexia, anemia, and increases in C-reactive protein (CRP) and ferritin
      were observed. Abdominal ultrasonography revealed a right adrenal gland tumor.
      Fractionated catecholamines and metanephrines in plasma and 24-h collected urine
      revealed elevated levels of norepinephrine and normetanephrine. Although
      hypertension and tachycardia were inapparent by an ordinary physical examination,
      paroxysmal mild hypertension and tachycardia were identified by a thorough
      examination after walking and abdominal compression. Paroxysmal hypertension and
      tachycardia were profound during operation. In conclusion, pheochromocytoma can
      be a consideration in the differential diagnosis of weight loss. Hypertension and
      tachycardia can be inapparent and paroxysmal in pediatric patients as well as in
      adults; thus, thorough assessment should be repeated.

PMID- 29662269
TI  - Two siblings with congenital central hypothyroidism caused by a novel mutation in
      the IGSF1 gene.
AB  - Genetic defects in the immunoglobulin superfamily member 1(IGSF1) protein are the
      cause of congenital central hypothyroidism (C-CH). Here we report two Japanese
      siblings with C-CH due to a novel IGSF1 mutation. The youngest brother showed a
      failure to thrive, hypothermia, and neonatal icterus six days after birth.
      Further endocrine evaluations led to the diagnosis of C-CH. In addition, PRL
      deficiency was later detected. In contrast, the elder brother did not show
      symptoms of severe hypothyroidism during the neonatal period, but he had been
      followed up by doctors due to psychomotor developmental delays since the age of 1
      yr. At the age of 3 yr, he had low thyroxine and PRL levels and was also
      diagnosed with C-CH. Because of the C-CH and PRL deficiency, an IGSF1 deficiency
      was suspected. Sequence analysis of the IGSF1 gene identified a novel hemizygous
      mutation of p.Trp1173GlyfsTer8 (NM_001170961.1:c.3517del) in both siblings. In
      conclusion, the phenotypic severity of C-CH is different, even in siblings.
      Importantly, an IGSF1 deficiency may result in severe hypothyroidism during the
      neonatal period.

PMID- 29662270
TI  - Recombinant human growth hormone in neonatal-onset multisystem inflammatory
      disease.

PMID- 29662271
TI  - Does growth-hormone treatment affect patients with and without a mitochondrial
      disorder differentially?

PMID- 29662273
TI  - Journey of a Research Article.

PMID- 29662272
TI  - Effect of bulk modulus on deformation of the brain under rotational
      accelerations.
AB  - Traumatic brain injury such as that developed as a consequence of blast is a
      complex injury with a broad range of symptoms and disabilities. Computational
      models of brain biomechanics hold promise for illuminating the mechanics of
      traumatic brain injury (TBI) and for developing preventive devices. However,
      reliable material parameters are needed for models to be predictive.
      Unfortunately, the properties of human brain tissue are difficult to measure, and
      the bulk modulus of brain tissue in particular is not well-characterized. Thus, a
      wide range of bulk modulus values are used in computational models of brain
      biomechanics, spanning up to three orders of magnitude in the differences between
      values. However, the sensitivity of these variations on computational predictions
      is not known. In this work, we study the sensitivity of a 3D computational human
      head model to various bulk modulus values. A subject-specific human head model
      was constructed from T1-weighted MRI images at 2 mm3 voxel resolution. Diffusion
      tensor imaging provided data on spatial distribution and orientation of axonal
      fiber-bundles for modeling white-matter anisotropy. Non-injurious, full-field
      brain deformations in a human volunteer were used to assess the simulated
      predictions. The comparison suggests that a bulk modulus value on the order of
      GPa gives the best agreement with experimentally measured in vivo deformation in
      the human brain. Further, simulations of injurious loading suggest that bulk
      modulus values on the order of GPa provide the closest match with the clinical
      findings in terms of predicated injured regions and extent of injury.

PMID- 29662274
TI  - From the desk of FOGSI President 2018.

PMID- 29662275
TI  - Short-Term Use of Injectable Contraception: An Effective Strategy for Safe
      Motherhood.

PMID- 29662276
TI  - Comparison Between Use of Oral Misoprostol Versus Vaginal Misoprostol for
      Induction of Labour at Term.
AB  - Background and Objective: In modern obstetrics, around 30% of cases require
      induction of labour for various reasons. Misoprostol is gaining popularity as
      pharmacological inducing agent, though the route and dosage of administration are
      not standardised. The objective of the study is to compare the safety and
      efficacy of the two routes of misoprostol administration-oral (100 MUg 4th
      hourly) and vaginal (25 MUg 4th hourly), for induction of labour at term.
      Methods: In this randomised trial, 104 women having crossed the expected date of
      delivery without going into spontaneous labour and cases which had premature
      rupture of membranes <12 h were considered for labour induction and were divided
      into two equal groups. Group A received 100 MUg misoprostol orally 4th hourly,
      and group B received 25 MUg misoprostol vaginally 4th hourly. Labour
      characteristics and maternal and foetal outcome were compared. Results: In terms
      of maternal outcome, mean number of doses for oral group is 2.73 and vaginal
      group is 3.04. In oral group, mean induction to vaginal delivery interval was 13
      h 43 min and in vaginal group interval is 13 h 26 min which was statistically not
      significant. The need for oxytocin augmentation was also statistically not
      significant. Both groups had equal number of failed inductions. Emergency LSCS
      done for foetal distress was more in vaginal group 2.9% compared to oral group
      which is 1%, but difference was not statistically significant (p value -0.55).
      Number of thick MSL in oral group was 3.2% as compared to vaginal group which is
      10.7% which was statistically significant (p value -0.04). APGAR score at 5 min
      7/10 was seen in 7.7% in vaginal group as compared to 0% in oral group which was
      also statistically significant (0.004). Number of NICU admissions was also more
      in vaginal group compared to oral group. Conclusion: Misoprostol in either oral
      or vaginal route has proven to be equally effective for inducing labour in women
      at term pregnancy. However, occurrence of lesser incidence of meconium-stained
      liquor and NICU admissions and fewer caesareans with better neonatal outcome in
      women induced with oral misoprostol outweighs its advantages over the vaginal
      misoprostol.

PMID- 29662277
TI  - The Importance of Cytogenetics and Associated Molecular Techniques in the
      Management of Patients Carrying Robertsonian Translocation and Their Pregnancy
      Outcome by Intracytoplasmic Sperm Injection.
AB  - Objective: The present study outlines three cases of a Robertsonian translocation
      and the consequences for the initiation of pregnancy by intracytoplasmic sperm
      injection (ICSI). Three case histories are presented documenting structural
      chromosome abnormalities in infertile males. Materials and Methods: Semen
      analysis was performed according to the World Health Organization guidelines.
      Chromosome analysis was performed using G-banding. Y chromosome microdeletions
      were detected by multiplex polymerase chain reaction assays. Results: Cytogenetic
      analysis revealed Robertsonian translocation 45,XY,der(14;21)(q10;q10) in a male
      with severe oligoasthenoteratozoospermia (SOAT) after three subsequent ICSI
      treatments were unsuccessful. The second case involved a Robertsonian
      translocation 45,XY,der(13,14)(q10;q10) with SOAT detected in a male after one
      pregnancy loss. Third case involved a Robertsonian translocation
      45,XY,der(13,14)(q10;q10) with SOAT. Conclusion: This case series emphasize the
      necessity of cytogenetic analysis of couples with primary infertility and
      recurrent miscarriages before any assisted reproductive technology is performed.
      For couples in whom one or more partners have a translocation, prenatal genetic
      diagnosis/preimplantation genetic diagnosis is recommended.

PMID- 29662278
TI  - Comparison of Efficacy of Bupivacaine with Dexmedetomidine Versus Bupivacaine
      Alone for Transversus Abdominis Plane Block for Post-operative Analgesia in
      Patients Undergoing Elective Caesarean Section.
AB  - Background: Increasing rate of Caesarean sections and inadequate pain relief
      following Caesarean section is seen in almost all parts of the world. Transversus
      abdominis plane block is gaining popularity as a part of multimodal analgesia for
      post-operative pain relief following abdominal surgeries. Aim: To compare
      bupivacaine and bupivacaine with dexmedetomidine in transversus abdominis plane
      block for pain relief after Caesarean section. Method: American Society of
      Anaesthesiologists I and II parturients with no comorbidities admitted for
      elective Caesarean section were included in the study. Thirty-five patients were
      in each study (with dex) and control (without dex) groups. At the end of
      Caesarean section done under spinal anaesthesia, transversus abdominis plane
      block was done bilaterally under ultrasound guidance using in-plane technique of
      needle insertion. 20 ml of 0.25% bupivacaine with 0.5 mcg/kg of dexmedetomidine
      in the study group and 20 ml of 0.25% bupivacaine in the control group were
      injected in the neurovascular plane. Results: Eight patients from the study group
      and 15 from the control group were given opioids as rescue analgesia. The average
      time at which rescue analgesia was first sought was 14.25 and 7.73 h in the study
      and control groups, respectively. The P value of this difference was 0.0136 and
      was found to be statistically significant. Conclusion: The addition of
      dexmedetomidine to bupivacaine in TAP block prolonged the duration of time at
      which first dose of rescue analgesia was sought and also reduced the total dose
      of opioid requirement in the first 24-h post-Caesarean section.

PMID- 29662279
TI  - There is Only a Modest Increase in Neonatal Respiratory Morbidity Following Early
      Term Elective Cesarean in a South Indian Population.
AB  - Objectives: Elective cesarean deliveries (ECD) are still performed prior to 39
      weeks. This study aimed to identify risk of neonatal respiratory morbidity (NRM)
      following ECD near term, in a South Indian population. Specifically, study aimed
      to measure the additional healthcare burden due to large number of ECDs performed
      prior to 39 weeks, in this local population. Methods: We analyzed NRM among 1329
      deliveries (584 ECD and 745 spontaneous vaginal delivery, SVD) in a tertiary
      hospital over 2 years. Neonates were grouped into: A: 35+0-36+6 weeks, B: 37+0
      38+6 weeks, and C: >=39 weeks. NRM was compared between ECD versus SVD. Results:
      Majority (433/584) of ECDs were performed between 37+0 and 38+6 weeks. Overall,
      32% received steroid prophylaxis. Of 1329 newborns, 18/584 (3.82%) in ECD and
      6/745 (0.8%) in SVD group developed NRM (p value of 0.004, OR 3.9, CI 1.54-9.93).
      Need of respiratory support among ECD was 4.28% compared to 0.53% in SVD (p <
      0.001, OR 8.28; CI 2.86-23.94). However, comparing neonates born by ECD between
      groups B Vs C; there was only a modest increase in NRM (2.07 vs 0.9%; p 0.48, OR
      2.3 with CI 0.29-18.4) and in need of respiratory support (2.54 vs 0.9%; p 0.47,
      OR 2.84; CI 0.36-22.2). Conclusion: NRM following early term ECD continues to be
      a healthcare burden in India. Interestingly in this South Indian population,
      early term ECDs caused only modest increase in NRM, and this ethnic variation
      requires further evaluation to determine ideal time for ECD in local population.

PMID- 29662280
TI  - Effects of Epidural Labour Analgesia in Mother and Foetus.
AB  - Objective: Aim of study was to determine effect of epidural analgesia on progress
      of labour and mode of delivery, to find out its complications in labour and
      puerperium and to evaluate neonatal outcome in terms of APGAR score. Method: The
      present study was conducted in Department of Obstetrics and Gynaecology at
      Government Medical College Aurangabad over period of 2 years from June 2014 to
      June 2016 after taking approval from institutional ethical board. Hundred low
      risk primigravidas were included in the study, 50 women received epidural
      analgesia for relief of labour pain at 3-4 cm and 50 women served as control. The
      important  outcome  FACTORS studied were the following : (1) duration of active
      phase of I stage, and II stage, (2) mode of delivery, (3) APGAR scores, (4)
      untoward reactions and intrapartum complications, (5) overall satisfaction of the
      mother. Results: The operative delivery rates were not significantly different in
      both the groups (8% in the control group and 6% in the study group: p value NS,
      i.e. > 0.05). The duration of first stage (our study showed no significant
      difference in the duration of first stage in both the study and control groups p
      value > 0.05) and second stage of labour (p value NS > 0.05) and the need for
      oxytocin were comparable in the two groups. The side effects observed were
      minimal. It has given excellent pain relief and improved neonatal outcome (5
      min). EA is associated with rates of vaginal delivery (88 v/s 84%) and LSCS rate
      (8 v/s 6%) which are comparable with control group. Conclusion: Epidural
      analgesia is a very promising, safe and effective method of pain relief. No major
      complications and a good APGAR score make it a good option of care in modern
      obstetrics.

PMID- 29662281
TI  - Role of AMH as Diagnostic Tool for Polycystic Ovarian Syndrome.
AB  - Background: To evaluate role of AMH as a diagnostic tool for PCOS. Methods: This
      was a prospective case-control study on women attending Gynae OPD of Dr RML
      Hospital, New Delhi, from 1 November 2015 to 31 March 2017. Study comprised of 45
      women with PCOS, diagnosed using Rotterdam criteria and 45 women as controls.
      Clinical history included oligomenorrhea, hirsutism, examination included BMI,
      Ferriman-Gallwey score, investigations included blood for FSH, LH, estradiol,
      TSH, prolactin, total testosterone, AMH level and pelvic USG which was done for
      all women. Results: Both PCOS cases and control were matched for age and BMI.
      Median AMH levels of 4.32 ng/ml in PCOS cases was almost twice that of 2.32 ng/ml
      in controls (p = 0.001). Maximum diagnostic potential of AMH alone for PCOS was
      at a cut-off of 3.44 ng/ml with sensitivity of 77.78% and specificity of 68.89%.
      AMH was used as an adjunct to existing Rotterdam criteria as the fourth parameter
      OA+HA+PCOM+AMH (any three out of four) yielded sensitivity of 80%. However, when
      PCOM in Rotterdam criteria was replaced by AMH, OA+HA+AMH (any two out of three)
      or OA/HA+AMH resulted in sensitivity of 86.67 and 71.11%, respectively.
      Conclusion: AMH levels were significantly higher in PCOS than in controls. AMH as
      an independent marker could not effectively diagnose PCOS. However, AMH levels as
      an adjunct to existing Rotterdam criteria for diagnosis of PCOS had good
      diagnostic potential.

PMID- 29662282
TI  - The Role of MGIT 960 Culture Medium in Resolving the Diagnostic Dilemma for
      Genital Tuberculosis Patients Presenting with Infertility.
AB  - Background: The purpose of this study was to assess the utility of Mycobacteria
      Growth Indicator Tube (MGIT) 960 culture medium for the diagnosis of genital
      tuberculosis (GTB) in women presenting with infertility. Methods: The
      premenstrual endometrial biopsy samples in 300 women presenting with primary and
      secondary infertility were subjected to AFB smear method, histopathological
      examination and culture on LJ and MGIT 960 media. Detection rates were compared
      for diagnostic modalities and their combinations. Results: In total, 30 cases
      were positive for genital tuberculosis by either of the four tests employed. The
      detection rates for AFB smear, MGIT culture, LJ culture and HPE were 50, 46.7,
      3.3 and 33.3%, respectively. A combination of smear examination for AFB, MGIT 960
      culture and histopathological examination was able to detect all the positive
      cases. A combination of MGIT and LJ media provided no added advantage over MGIT
      alone since the only case where LJ culture was positive had been detected by
      positive MGIT culture. In as many as five positive cases (16.7%), only MGIT
      culture was positive. Conclusion: The addition of MGIT 960 culture medium to
      routine battery of investigations in infertility patients significantly improves
      the diagnosis.

PMID- 29662283
TI  - Intrauterine Copper Device (CuT380A) as a Contraceptive Method in the Indian
      Context: Acceptability, Safety and Efficacy Depending on the Timing of Insertion.
AB  - Background: Ideal time of Intrauterine copper device (IUCD) insertion either to
      space or limit births in Indian women should be known to check fertility
      effectively and safely. We therefore aimed to compare various IUCD related
      clinical factors to assess its acceptability, safety and efficacy in immediate
      postpartum vaginal insertion, intra-caesarean insertion, delayed postpartum
      insertion and interval insertion at a tertiary-care centre in India. Methods: It
      was a retrospective analysis of prospectively collected data from July 2013 to
      July 2014. Data was reviewed about maternal age, socioeconomic status, education,
      occupation and parity of a total of 1631 eligible mothers and was compared
      between postpartum group and interval group. Data about spontaneous expulsion
      rate of IUCD, proportion of patients not able to feel thread, reasons for removal
      and failure rate of IUCD up to a follow-up period of 6 months was also collected
      in these women and compared among immediate vaginal insertion, intra-caesarean
      insertion, delayed postpartum insertion and interval insertion. Results: Majority
      of women were between 20 and 35 years of age group, literate, multiparous,
      unemployed and belonged to middle/lower socio-economic strata in both postpartum
      and interval groups. Spontaneous expulsion rates were 1.84, 0.84, 2.83 and 1.63%;
      proportions of patients not able to feel thread were 3.07, 8.73, 4.45 and 1.63%;
      and removal rates were 7.99, 6.48, 7.69 and 3.47% in immediate vaginal, intra
      caesarean, delayed postpartum and interval insertion groups, respectively.
      Failure was seen in only one case of delayed postpartum insertion. Conclusion:
      IUCD was more acceptable among young, literate and multiparous women as a
      contraceptive method. Immediate postpartum period was the safest and most
      efficacious time for IUCD insertion with least expulsion rate, maximum
      continuation rate and no failure and, therefore, should be encouraged by adequate
      counseling of mothers.

PMID- 29662284
TI  - A Comparative Study on Quantitative Assessment of Blood Flow and Vascularization
      in Polycystic Ovary Syndrome Patients and Normal Women Using Three-Dimensional
      Power Doppler Ultrasonography.
AB  - Purpose of the Study: To compare the quantitative assessment of blood flow and
      vascularization of ovaries in polycystic ovary syndrome patients and normal women
      using three-dimensional power Doppler ultrasonography. Methods: This cross
      sectional quantitative study was conducted on women of reproductive age group (15
      45 years) attending Gynaecology OPD AIMSR, Bathinda, Punjab. Thirty women were
      enrolled in polycystic ovarian syndrome (PCOS) group and 30 healthy women in
      control group. Women were categorized as polycystic ovary syndrome according to
      Rotterdam's criteria. The women with PCOS underwent transvaginal USG Doppler on
      day 6 of the cycle using 3D power Doppler USG equipment (GE Voluson E8), and
      vascularization index (VI), flow index (FI) and vascularization flow index (VFI)
      were measured. Results: The mean values of VI, FI and VFI measured by power
      Doppler ultrasonography were significantly increased (P value = 0.000) in women
      with PCOS when compared with healthy women. Conclusion: This study suggests that
      blood flow and vascularization measured by 3D power Doppler ultrasonography in
      ovaries of polycystic ovary syndrome patients were significantly more than the
      ovaries of normal women.

PMID- 29662285
TI  - Ex Utero Intrapartum Treatment (EXIT) for a Large Fetal Neck Mass.

PMID- 29662286
TI  - A Rare Case of Multiple Pelvic Hydatid Cyst.

PMID- 29662287
TI  - The "Saturday Effect" in Obstetrics: A Comparison Between Referral Patterns on
      Saturday and Other Days of the Week.

PMID- 29662288
TI  - Nonalcoholic fatty liver disease and liver transplantation - Where do we stand?
AB  - Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) is a
      challenging and multisystem disease that has a high socioeconomic impact.
      NAFLD/NASH is a main cause of macrovesicular steatosis and has multiple impacts
      on liver transplantation (LT), on patients on the waiting list for transplant, on
      post-transplant setting as well as on organ donors. Current data indicate new
      trends in the area of chronic liver disease. Due to the increased incidence of
      metabolic syndrome (MetS) and its components, NASH cirrhosis and hepatocellular
      carcinoma caused by NASH will soon become a major indication for LT. Furthermore,
      due to an increasing incidence of MetS and, consequently, NAFLD, there will be
      more steatotic donor livers and less high quality organs available for LT, in
      addition to a lack of available liver allografts. Patients who have NASH and are
      candidates for LT have multiple comorbidities and are unique LT candidates.
      Finally, we discuss long-term grafts and patient survival after LT, the
      recurrence of NASH and NASH appearing de novo after transplantation. In addition,
      we suggest topics and areas that require more research for improving the health
      care of this increasing patient population.

PMID- 29662289
TI  - Hepatitis B virus pre-S/S variants in liver diseases.
AB  - Chronic hepatitis B is a global health problem. The clinical outcomes of chronic
      hepatitis B infection include asymptomatic carrier state, chronic hepatitis (CH),
      liver cirrhosis (LC), and hepatocellular carcinoma (HCC). Because of the
      spontaneous error rate inherent to viral reverse transcriptase, the hepatitis B
      virus (HBV) genome evolves during the course of infection under the antiviral
      pressure of host immunity. The clinical significance of pre-S/S variants has
      become increasingly recognized in patients with chronic HBV infection. Pre-S/S
      variants are often identified in hepatitis B carriers with CH, LC, and HCC, which
      suggests that these naturally occurring pre-S/S variants may contribute to the
      development of progressive liver damage and hepatocarcinogenesis. This paper
      reviews the function of the pre-S/S region along with recent findings related to
      the role of pre-S/S variants in liver diseases. According to the mutation type,
      five pre-S/S variants have been identified: pre-S deletion, pre-S point mutation,
      pre-S1 splice variant, C-terminus S point mutation, and pre-S/S nonsense
      mutation. Their associations with HBV genotype and the possible pathogenesis of
      pre-S/S variants are discussed. Different pre-S/S variants cause liver diseases
      through different mechanisms. Most cause the intracellular retention of HBV
      envelope proteins and induction of endoplasmic reticulum stress, which results in
      liver diseases. Pre-S/S variants should be routinely determined in HBV carriers
      to help identify individuals who may be at a high risk of less favorable liver
      disease progression. Additional investigations are required to explore the
      molecular mechanisms of the pre-S/S variants involved in the pathogenesis of each
      stage of liver disease.

PMID- 29662290
TI  - Extra-intestinal manifestations of non-celiac gluten sensitivity: An expanding
      paradigm.
AB  - Non celiac gluten sensitivity (NCGS) is a syndrome characterized by a cohort of
      symptoms related to the ingestion of gluten-containing food in subjects who are
      not affected by celiac disease (CD) or wheat allergy. The possibility of systemic
      manifestations in this condition has been suggested by some reports. In most
      cases they are characterized by vague symptoms such as 'foggy mind', headache,
      fatigue, joint and muscle pain, leg or arm numbness even if more specific
      complaints have been described. NCGS has an immune-related background. Indeed
      there is a strong evidence that a selective activation of innate immunity may be
      the trigger for NCGS inflammatory response. The most commonly autoimmune
      disorders associated to NCGS are Hashimoto thyroiditis, dermatitis herpetiformis,
      psoriasis and rheumatologic diseases. The predominance of Hashimoto thyroiditis
      represents an interesting finding, since it has been indirectly confirmed by an
      Italian study, showing that autoimmune thyroid disease is a risk factor for the
      evolution towards NCGS in a group of patients with minimal duodenal inflammation.
      On these bases, an autoimmune stigma in NCGS is strongly supported; it could be a
      characteristic feature that could help the diagnosis and be simultaneously
      managed. A possible neurological involvement has been underlined by NCGS
      association with gluten ataxia, gluten neuropathy and gluten encephalopathy. NCGS
      patients may show even psychiatric diseases such as depression, anxiety and
      psychosis. Finally, a link with functional disorders (irritable bowel syndrome
      and fibromyalgia) is a topic under discussion. In conclusion, the novelty of this
      matter has generated an expansion of literature data with the unavoidable
      consequence that some reports are often based on low levels of evidence.
      Therefore, only studies performed on large samples with the inclusion of control
      groups will be able to clearly establish whether the large information from the
      literature regarding extra-intestinal NCGS manifestations could be supported by
      evidence-based agreements.

PMID- 29662291
TI  - Punctual mutations in 23S rRNA gene of clarithromycin-resistant Helicobacter
      pylori in Colombian populations.
AB  - AIM: To characterize punctual mutations in 23S rRNA gene of clarithromycin
      resistant Helicobacter pylori (H. pylori) and determine their association with
      therapeutic failure. METHODS: PCR products of 23S rRNA gene V domain of 74 H.
      pylori isolates; 34 resistant to clarithromycin (29 from a low-risk gastric
      cancer (GC) population: Tumaco-Colombia, and 5 from a high-risk population:
      Tuquerres-Colombia) and 40 from a susceptible population (28 from Tumaco and 12
      from Tuquerres) were sequenced using capillary electrophoresis. The concordance
      between mutations of V domain 23S rRNA gene of H. pylori and therapeutic failure
      was determined using the Kappa coefficient and McNemar's test was performed to
      determine the relationship between H. pylori mutations and clarithromycin
      resistance. RESULTS: 23S rRNA gene from H. pylori was amplified in 56/74
      isolates, of which 25 were resistant to clarithromycin (20 from Tumaco and 5 from
      Tuquerres, respectively). In 17 resistant isolates (13 from Tumaco and 4 from
      Tuquerres) the following mutations were found: A1593T1, A1653G2, C1770T, C1954T1,
      and G1827C in isolates from Tumaco, and A2144G from Tuquerres. The mutations
      T2183C, A2144G and C2196T in H. pylori isolates resistant to clarithromycin from
      Colombia are reported for the first time. No association between the H. pylori
      mutations and in vitro clarithromycin resistance was found. However, therapeutic
      failure of eradication treatment was associated with mutations of 23S rRNA gene
      in clarithromycin-resistant H. pylori (kappa = 0.71). CONCLUSION: The therapeutic
      failure of eradication treatment in the two populations from Colombia was
      associated with mutations of the 23S rRNA gene in clarithromycin-resistant H.
      pylori.

PMID- 29662292
TI  - Post-polypectomy bleeding and thromboembolism risks associated with warfarin vs
      direct oral anticoagulants.
AB  - AIM: To verify the validity of the endoscopy guidelines for patients taking
      warfarin or direct oral anticoagulants (DOAC). METHODS: We collected data from
      218 patients receiving oral anticoagulants (73 DOAC users, 145 warfarin users)
      and 218 patients not receiving any antithrombotics (age- and sex-matched
      controls) who underwent polypectomy. (1) We evaluated post-polypectomy bleeding
      (PPB) risk in patients receiving warfarin or DOAC compared with controls; (2) we
      assessed the risks of PPB and thromboembolism between three AC management
      methods: Discontinuing AC with heparin bridge (HPB) (endoscopy guideline
      recommendation), continuing AC, and discontinuing AC without HPB. RESULTS: PPB
      rate was significantly higher in warfarin users and DOAC users compared with
      controls (13.7% and 13.7% vs 0.9%, P < 0.001), but was not significantly
      different between rivaroxaban (13.2%), dabigatran (11.1%), and apixaban (13.3%)
      users. Two thromboembolic events occurred in warfarin users, but none in DOAC
      users. Compared with the continuing anticoagulant group, the discontinuing
      anticoagulant with HPB group (guideline recommendation) had a higher PPB rate
      (10.8% vs 19.6%, P = 0.087). These findings were significantly evident in
      warfarin but not DOAC users. One thrombotic event occurred in the discontinuing
      anticoagulant with HPB group and the discontinuing anticoagulant without HPB
      group; none occurred in the continuing anticoagulant group. CONCLUSION: PPB risk
      was similar between patients taking warfarin and DOAC. Thromboembolism was
      observed in warfarin users only. The guideline recommendations for HPB should be
      re-considered.

PMID- 29662293
TI  - Maintenance for healed erosive esophagitis: Phase III comparison of vonoprazan
      with lansoprazole.
AB  - AIM: To compare vonoprazan 10 and 20 mg vs lansoprazole 15 mg as maintenance
      therapy in healed erosive esophagitis (EE). METHODS: A total of 607 patients aged
      >= 20 years, with endoscopically-confirmed healed EE following 8 wk of treatment
      with vonoprazan 20 mg once daily, were randomized 1:1:1 to receive lansoprazole
      15 mg (n = 201), vonoprazan 10 mg (n = 202), or vonoprazan 20 mg (n = 204), once
      daily. The primary endpoint of the study was the rate of endoscopically-confirmed
      EE recurrence during a 24-wk maintenance period. The secondary endpoint was the
      EE recurrence rate at Week 12 during maintenance treatment. Additional efficacy
      endpoints included the incidence of heartburn and acid reflux, and the EE healing
      rate 4 wk after the initiation of maintenance treatment. Safety endpoints
      comprised adverse events (AEs), vital signs, electrocardiogram findings, clinical
      laboratory results, serum gastrin and pepsinogen I/II levels, and gastric mucosa
      histopathology results. RESULTS: Rates of EE recurrence during the 24-wk
      maintenance period were 16.8%, 5.1%, and 2.0% with lansoprazole 15 mg, vonoprazan
      10 mg, and vonoprazan 20 mg, respectively. Vonoprazan was shown to be non
      inferior to lansoprazole 15 mg (P < 0.0001 for both doses). In a post-hoc
      analysis, EE recurrence at Week 24 was significantly reduced with vonoprazan at
      both the 10 mg and the 20 mg dose vs lansoprazole 15 mg (5.1% vs 16.8%, P =
      0.0002, and 2.0% vs 16.8%, P < 0.0001, respectively); by contrast, the EE
      recurrence rate did not differ significantly between the two doses of vonoprazan
      (P = 0.1090). The safety profiles of vonoprazan 10 and 20 mg were similar to that
      of lansoprazole 15 mg in patients with healed EE. Treatment-related AEs were
      reported in 11.4%, 10.4%, and 10.3% of patients in the lansoprazole 15 mg,
      vonoprazan 10 mg, and vonoprazan 20 mg arms, respectively. CONCLUSION: Our
      findings confirm the non-inferiority of vonoprazan 10 and 20 mg to lansoprazole
      15 mg as maintenance therapy for patients with healed EE.

PMID- 29662294
TI  - Application of enhanced recovery after gastric cancer surgery: An updated meta
      analysis.
AB  - AIM: To provide an updated assessment of the safety and efficacy of enhanced
      recovery after surgery (ERAS) protocols in elective gastric cancer (GC) surgery.
      METHODS: PubMed, Medline, EMBASE, World Health Organization International Trial
      Register, and Cochrane Library were searched up to June 2017 for all available
      randomized controlled trials (RCTs) comparing ERAS protocols and standard care
      (SC) in GC surgery. Thirteen RCTs, with a total of 1092 participants, were
      analyzed in this study, of whom 545 underwent ERAS protocols and 547 received SC
      treatment. RESULTS: No significant difference was observed between ERAS and
      control groups regarding total complications (P = 0.88), mortality (P = 0.50) and
      reoperation (P = 0.49). The incidence of pulmonary infection was significantly
      reduced (P = 0.03) following gastrectomy. However, the readmission rate after GC
      surgery nearly tripled under ERAS (P = 0.009). ERAS protocols significantly
      decreased the length of postoperative hospital stay (P < 0.00001) and medical
      costs (P < 0.00001), and accelerated bowel function recovery, as measured by
      earlier time to the first flatus (P = 0.0004) and the first defecation (P <
      0.0001). Moreover, ERAS protocols were associated with a lower level of serum
      inflammatory response, higher serum albumin, and superior short-term quality of
      life (QOL). CONCLUSION: Collectively, ERAS results in accelerated convalescence,
      reduction of surgical stress and medical costs, improved nutritional status, and
      better QOL for GC patients. However, high-quality multicenter RCTs with large
      samples and long-term follow-up are needed to more precisely evaluate ERAS in
      radical gastrectomy.

PMID- 29662295
TI  - Should hot biopsy forceps be abandoned for polypectomy of diminutive colorectal
      polyps?
AB  - Standardized approach to polypectomy of diminutive colorectal polyps (DCPs) is
      lacking since cold biopsy forceps have been associated with high levels of
      recurrence, hot biopsy forceps are considered inadequate and risky and cold
      snaring is currently under investigation for its efficacy and safety. This has
      led to confusion and a gap in clinical practice. This article discusses the
      usefulness and contemporary practical applicability of hot biopsy forceps and
      provides well-intentioned criticism of the new European guidelines for the
      treatment of DCPs. Diminutive colorectal polyps are a source of frustration for
      the endoscopist since their small size is accompanied by a considerable risk of
      premalignant neoplasia and a small but non-negligible risk of advanced neoplasia
      and even cancer. Since the proportion of diminutive colorectal polyps is
      substantial and exceeds that of larger polyps, their effective removal poses a
      considerable workload and a therapeutic challenge. During the last decade, the
      introduction of cold snaring to routine endoscopy practice has attempted to
      overcome the use of prior techniques, such as hot biopsy forceps. It is important
      to recognize that with the exception of endoscopic methods that are obviously
      unsafe and inadequate to serve their purpose, all other interventional endoscopic
      methods are operator-dependent in the sense that specific expertise and training
      are obligatory for the success of any therapeutic intervention. Since relevant
      publications on hot biopsy forceps are still in favor of its careful use, as it
      has not yet demonstrated inferiority compared with newer techniques, it would be
      prudent for any medical practitioner to evaluate the available tools and judge
      any new proposed technique based on the evidence before it is adopted.

PMID- 29662296
TI  - Power in Bayesian Mediation Analysis for Small Sample Research.
AB  - It was suggested that Bayesian methods have potential for increasing power in
      mediation analysis (Koopman, Howe, Hollenbeck, & Sin, 2015; Yuan & MacKinnon,
      2009). This paper compares the power of Bayesian credibility intervals for the
      mediated effect to the power of normal theory, distribution of the product,
      percentile, and bias-corrected bootstrap confidence intervals at N<= 200.
      Bayesian methods with diffuse priors have power comparable to the distribution of
      the product and bootstrap methods, and Bayesian methods with informative priors
      had the most power. Varying degrees of precision of prior distributions were also
      examined. Increased precision led to greater power only when N>= 100 and the
      effects were small, N < 60 and the effects were large, and N < 200 and the
      effects were medium. An empirical example from psychology illustrated a Bayesian
      analysis of the single mediator model from prior selection to interpreting
      results.

PMID- 29662297
TI  - Graphics Processing Unit-Enhanced Genetic Algorithms for Solving the Temporal
      Dynamics of Gene Regulatory Networks.
AB  - Understanding the regulation of gene expression is one of the key problems in
      current biology. A promising method for that purpose is the determination of the
      temporal dynamics between known initial and ending network states, by using
      simple acting rules. The huge amount of rule combinations and the nonlinear
      inherent nature of the problem make genetic algorithms an excellent candidate for
      finding optimal solutions. As this is a computationally intensive problem that
      needs long runtimes in conventional architectures for realistic network sizes, it
      is fundamental to accelerate this task. In this article, we study how to develop
      efficient parallel implementations of this method for the fine-grained parallel
      architecture of graphics processing units (GPUs) using the compute unified device
      architecture (CUDA) platform. An exhaustive and methodical study of various
      parallel genetic algorithm schemes-master-slave, island, cellular, and hybrid
      models, and various individual selection methods (roulette, elitist)-is carried
      out for this problem. Several procedures that optimize the use of the GPU's
      resources are presented. We conclude that the implementation that produces better
      results (both from the performance and the genetic algorithm fitness
      perspectives) is simulating a few thousands of individuals grouped in a few
      islands using elitist selection. This model comprises 2 mighty factors for
      discovering the best solutions: finding good individuals in a short number of
      generations, and introducing genetic diversity via a relatively frequent and
      numerous migration. As a result, we have even found the optimal solution for the
      analyzed gene regulatory network (GRN). In addition, a comparative study of the
      performance obtained by the different parallel implementations on GPU versus a
      sequential application on CPU is carried out. In our tests, a multifold speedup
      was obtained for our optimized parallel implementation of the method on medium
      class GPU over an equivalent sequential single-core implementation running on a
      recent Intel i7 CPU. This work can provide useful guidance to researchers in
      biology, medicine, or bioinformatics in how to take advantage of the
      parallelization on massively parallel devices and GPUs to apply novel
      metaheuristic algorithms powered by nature for real-world applications (like the
      method to solve the temporal dynamics of GRNs).

PMID- 29662298
TI  - Anti-VEGF treatment of macular edema associated with retinal vein occlusion:
      patterns of use and effectiveness in clinical practice (ECHO study report 2).
AB  - Purpose: To evaluate the efficacy, safety, and injection frequency of vascular
      endothelial growth factor (VEGF) antagonists in the treatment of macular edema
      secondary to retinal vein occlusion (RVO) in clinical practice. Patients and
      methods: A multicenter retrospective study of the medical records of 165 patients
      (95 branch RVO, 70 central RVO) treated with at least three anti-VEGF injections
      in the study eye was conducted. Available data collected for at least 6 months
      after the first injection included Snellen best-corrected visual acuity (BCVA),
      central retinal thickness (CRT) by time-domain optical coherence tomography (TD
      OCT) or spectral-domain optical coherence tomography (SD-OCT), anti-VEGF
      injections, other treatments/procedures for RVO, and adverse events. Results: At
      baseline prior to anti-VEGF treatment, mean BCVA was 20/80 Snellen equivalent and
      mean CRT was 499 MUm. Mean number of anti-VEGF injections received was 7.1 during
      the first year, 5.4 during the second year, and 5.9 during the third year; 51.3%
      (842/1,641) of injections were ranibizumab, 44.1% (724/1,641) were bevacizumab,
      and 4.6% (75/1,641) were aflibercept. One in five patients received concomitant
      focal laser treatment. The percentage of patients achieving both BCVA of 20/40 or
      better and CRT <=250 MUm on TD-OCT or <=300 MUm on SD-OCT at the same visit
      (primary endpoint) was 26.1% (30/115) after the first anti-VEGF injection and
      ranged from 20.0% (7/35) to 36.7% (11/30) after the first 16 injections. After
      each anti-VEGF injection from the 1st to the 16th, <60% of patients achieved
      20/40 or better BCVA and <=70% of patients achieved CRT <=250 MUm on TD-OCT or
      <=300 MUm on SD-OCT. The most common treatment-related adverse event was blurry
      or cloudy vision. Conclusion: In this real-world study, a mean of five to seven
      anti-VEGF injections was administered yearly, and the response to anti-VEGF
      therapy was suboptimal in many patients. Anti-VEGF therapy was well tolerated.

PMID- 29662299
TI  - Clinical characteristics and causes of visual impairment in a low vision clinic
      in northern Jordan.
AB  - Aim: The aim of the study was to identify causes of visual impairment among
      patients attending a low vision clinic in the north of Jordan and to study the
      relevant demographic characteristics of these patients. Subjects and methods: The
      retrospective study was conducted through a review of clinical records of 135
      patients who attended a low vision clinic in Irbid. Clinical characteristics of
      the patients were collected, including age, gender, primary cause of low vision,
      best corrected visual acuity, and current prescribed low vision aids. Descriptive
      statistics analysis using numbers and percentages were calculated to summarize
      categorical and nominal data. Results: A total of 135 patients (61 [45.2%]
      females and 74 [54.8%] males) were recruited in the study. Mean age +/- standard
      deviation for the study population was 24.53 +/- 16.245 years; age range was 5-90
      years. Of the study population, 26 patients (19.3%) had mild visual impairment,
      61 patients (45.2%) had moderate visual impairment, 27 patients (20.0%) had
      severe visual impairment, and 21 patients (15.6%) were blind. The leading causes
      of visual impairment across all age groups were albinism (31.9%) and retinitis
      pigmentosa (RP) (18.5%). Albinism also accounted for the leading cause of visual
      impairment among the pediatric age group (0-15 years) while albinism, RP, and
      keratoconus were the primary causes of visual impairment for older patients. A
      total of 59 patients (43.7%) were given low vision aids either for near or
      distance. The only prescribed low vision aids for distances were telescopes. For
      near, spectacle-type low vision aid was the most commonly prescribed low vision
      aids. Conclusion: Low vision services in Jordan are still very limited. A
      national strategy programme to increase awareness of low vision services should
      be implemented, and health care policies should be enforced to cover low vision
      aids through the national medical insurance.

PMID- 29662300
TI  - The effects of repeated Ozurdex injections on ocular hypertension.
AB  - Purpose: The purpose of this study was to correlate the degree of ocular
      hypertension with the number of Ozurdex injections. Methods: Intraocular pressure
      (IOP) fluctuations for a total of 183 injections were studied over a period of at
      least 12 months. The main indications for treatment were uveitis, diabetic
      macular edema, and retinal vein occlusion. Results: Results of the study
      demonstrate that repeated Ozurdex injections do not increase the frequency of IOP
      spikes beyond 30 mmHg. For lower IOPs, however, a positive correlation exists.
      Furthermore, patients with primary open angle glaucoma and uveitis had the
      highest IOP response to repeated injections. On average, patients with an IOP of
      >=28.6 mmHg received pressure lowering medications, after which their IOP reached
      a stable level (16.7 mmHg) without the need for additional interventions.
      Conclusion: The data support the conclusion that multiple Ozurdex injections does
      not increase the frequency of IOP spikes beyond 30 mmHg, but patients still must
      be closely monitored if they have a history of primary open angle glaucoma.

PMID- 29662301
TI  - Conventional trabeculectomy versus trabeculectomy with the Ex-PRESS(r) mini
      glaucoma shunt: differences in postoperative interventions.
AB  - Purpose: To compare the postoperative interventions and outcomes between
      conventional trabeculectomy and trabeculectomy with the Ex-PRESS(r) mini-glaucoma
      shunt device (Ex-Press). Methods: This was a retrospective, comparative, single
      facility study. We analyzed the cases of 108 glaucoma patients who underwent
      trabeculectomy and were followed for >1 year. Thirty-nine eyes underwent a
      conventional trabeculectomy (conventional group) and 69 eyes underwent a
      trabeculectomy with an Ex-Press (Ex-Press group). As evaluation items, we
      examined postoperative intraocular pressure (IOP), the surgical success rate,
      postoperative complications, the number of days to laser suture lysis, and
      needling. Results: Trabeculectomy significantly decreased the patients' IOP
      values from 27.8+/-7.9 to 11.1+/-3.9 mmHg in the conventional group (p<0.001) and
      from 27.7+/-9.2 to 11.5+/-3.7 mmHg in the Ex-Press group (p<0.001) after 1 year.
      The success rate was not significantly different between the groups. The timing
      of the first laser suture lysis was significantly sooner in the Ex-Press group,
      and the Ex-Press group showed significantly less choroidal detachment due to low
      IOP. Conclusion: Earlier laser suture lysis in patients whose trabeculectomy
      treatment includes an Ex-Press is required to obtain the outcomes comparable to
      those of conventional trabeculectomy.

PMID- 29662302
TI  - Hot-water extract of the branches of Hovenia dulcis Thunb. (Rhamnaceae)
      ameliorates low-fiber diet-induced constipation in rats.
AB  - Hovenia dulcis Thunb. (Rhamnaceae), also known as oriental raisin tree, is used
      in traditional herbal medicine. Its extracts have been reported to show various
      pharmacological effects such as hepatoprotection, antitumor, antiatopic
      dermatitis, antilipid peroxidation, anti-steatotic, anti-inflammatory, and
      antiallergic activities. However, there have been no reports on the effect of H.
      dulcis extracts in relieving constipation so far. The aim of this study was to
      investigate the effects of a hot-water extract of the branches of H. dulcis
      (WEHD) on low-fiber diet-induced constipation in Sprague Dawley rats. The in vivo
      laxative activity of WEHD was assessed by measuring the intestinal transit of
      charcoal meal and stool parameters. Furthermore, the in vitro spasmogenic
      activity of WEHD was evaluated by monitoring the temporal profiles of contraction
      of rat colon in the absence or presence of WEHD. In addition, constituent
      profiling was conducted using high-performance liquid chromatography analysis.
      Pretreatment with WEHD significantly enhanced the intestinal transit of charcoal
      meal and increased the frequency and weight of stools in rats. In addition, the
      frequency and amplitude of contractile responses of isolated rat colon were
      markedly enhanced by WEHD. Two organic phenolic acids, ferulic and vanillic
      acids, were identified in WEHD, of which vanillic acid exhibited spasmogenic
      activity. To the best of our knowledge, this is the first study to report the
      laxative and spasmogenic activities of H. dulcis and its constituents, suggesting
      that WEHD can serve as a complementary and/or alternative laxative in alleviating
      chronic constipation.

PMID- 29662303
TI  - The effectiveness of long-term course of Sterimar Mn nasal spray for treatment of
      the recurrence rates of acute allergic rhinitis in patients with chronic allergic
      rhinitis.
AB  - Background: The "cost of illness" of the acute allergic rhinitis (AR) episodes in
      patients with chronic AR is very high in terms of therapy and quality of life. AR
      represents a worldwide health problem; despite the fact that many standardized
      treatments have been proposed and used, the recurrence rate of acute rhinitis
      episodes in springtime is always higher. Materials and methods: Sixty consecutive
      patients (13 F and 17 M in group A, 15 F and 15 M in group B; p=0.60) with
      chronic AR were enrolled in this prospective, controlled clinical trial. Thirty
      patients were treated daily for the same 5 months of the following year (2013)
      with isotonic seawater nasal spray enriched with manganese (Sterimar Mn; 4
      puffs/day), whereas 30 patients received only the standard care and were used as
      control group. Results: A 5 months course treatment with the nasal Sterimar Mn
      was able to decrease, significantly (p<0.001), the number of episodes of acute AR
      (6.33 episodes in the group of treated patients versus 9.33 episodes in control
      group). Also, the 5 months quality of life reduced over time (Visual Analogue
      Scale 5th month 9.90 in treated group versus Visual Analogue Scale 5th month 8.72
      in control group: p<0.001) without the typical adverse effects of the AR standard
      care therapy. Conclusion: This study shows the effectiveness of the use of
      Sterimar Mn for a 5 months therapy in terms of reduction of the number of
      episodes of acute AR and effectiveness of intrasubject improvement of Visual
      Analog Scale (quality of life).

PMID- 29662304
TI  - Chrysin suppresses proliferation, migration, and invasion in glioblastoma cell
      lines via mediating the ERK/Nrf2 signaling pathway.
AB  - Background: Chrysin, an active natural bioflavonoid, has been proven to protect
      against carcinogenesis. However, the role of chrysin in glioblastoma and the
      potential molecular mechanisms remain to be elucidated. In our previous study, we
      found that nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) is highly
      expressed in a variety of glioblastoma cell lines associated with the mitogen
      activated protein kinase (MAPK) pathway. The aim of this study was to evaluate
      the antitumor effects of chrysin in glioblastoma cells and how chrysin is related
      to the MAPK/Nrf2 signaling pathway. Methods: A Cell Counting Kit-8 assay and a
      plate colony formation assay were performed to evaluate cell proliferation. Cell
      migration ability was tested by a wound-healing assay. Transwell migration and
      Matrigel invasion assay were used to test the migration and invasion potential of
      cells. Nrf2 was knocked down by shRNA transfection. Protein expression was
      determined by Western blotting and immunofluorescence staining. The in vivo
      anticancer effect was measured using tumor xenografts in nude mice. Results:
      Chrysin inhibited the proliferation, migration, and invasion capacity of
      glioblastoma cells in dose- and time-dependent manners. Mechanistically, chrysin
      deactivated the Nrf2 signaling pathway by decreasing the translocation of Nrf2
      into the nucleus and suppressing the expression of hemeoxygenase-1 (HO-1) and
      NAD(P)H quinine oxidoreductase-1, meanwhile, Nrf2 shRNA attenuated the anticancer
      activity of chrysin. Furthermore, chrysin downregulated the protein expression of
      p-extracellular signal-regulated kinase 1 and 2 (ERK1/2), but did not
      significantly affect p-JNK and p-P38 expression levels. However, the
      downregulated level of Nrf2 and the antitumor effect of chrysin in glioblastoma
      cell lines were partially abrogated by the ERK1/2 signaling inhibitor (U0126).
      Finally, chrysin inhibited tumor growth in U87 xenografts. Conclusion: Our
      results show that chrysin exerts anticancer activity in glioblastoma cell lines
      possibly via the ERK/Nrf2 signaling pathway and indicate the potential
      application of chrysin as a natural sensitizer in chemotherapy.

PMID- 29662305
TI  - Parental preference and perspectives on continuous pulse oximetry in infants and
      children with bronchiolitis.
AB  - Objective: The purpose of the study was to investigate parental preference of
      continuous pulse oximetry in infants and children with bronchiolitis. Materials
      and methods: A cross-sectional prospective study was conducted at Hamad Medical
      Corporation in Qatar. Parents of infants and children <24 months old and
      hospitalized with bronchiolitis were offered an interview survey. Results: A
      total of 132 questionnaires were completed (response rate 100%). Approximately
      90% of participants were 20-40 years of age, and 85% were females. The mean age
      of children was 7.2+/-5.8 months. Approximately eight in ten parents supported
      the idea of continuous pulse oximetry in children with bronchiolitis. Almost 43%
      of parents believed that continuous pulse-oximetry monitoring would delay their
      children's hospital discharge. Interestingly, approximately 85% of caregivers
      agreed that continuous pulse oximetry had a good impact on their children's
      health. In addition, around one in two of the participants stated that good
      bedside examinations can obviate the need for continuous pulse oximetry.
      Furthermore, 80% of parents believed that continuous pulse-oximetry monitoring
      would give the health-care provider a good sense of security regarding the
      child's health. Finally, being a male parent was associated with significantly
      increased risk of reporting unnecessary fatigue, attributed to the sound of
      continuous pulse oximetry (P=0.031). Conclusion: Continuous pulse-oximetry
      monitoring in children with bronchiolitis was perceived as reassuring for
      parents. Involving parents in decision-making is considered essential in the
      better management of children with bronchiolitis or any other disease. The first
      step to decrease continuous pulse oximetry will require provider education and
      change as well. Furthermore, we recommend proper counseling for parents,
      emphasizing that medical technology is not always essential, but is a
      complementary mode of managing a disease.

PMID- 29662306
TI  - Short-term vascular hemodynamic responses to isometric exercise in young adults
      and in the elderly.
AB  - Background: Vascular aging is known to induce progressive stiffening of the large
      elastic arteries, altering vascular hemodynamics under both rest and stress
      conditions. In this study, we aimed to investigate changes in vascular
      hemodynamics in response to isometric handgrip exercise across ages. Participants
      and methods: We included 62 participants, who were divided into three age
      categories: 20-40 (n=22), 41-60 (n=20), and 61-80 (n=20) years. Vascular
      hemodynamics were measured using the Mobil-o-Graph(r) based on the pulsatile
      pressure changes in the brachial artery. One-way ANOVA test was performed to
      analyze the changes induced by isometric handgrip exercise. Results: After
      isometric handgrip exercise, aortic pulse wave velocity (PWV) increased by 0.10
      m/s in the youngest, 0.06 m/s in the middle-age, and 0.02 m/s in the oldest age
      category. Changes in PWV strongly correlated with those in central systolic blood
      pressure (cSBP) (r=0.878, P<0.01). After isometric exercise, the mean change of
      systolic blood pressure (SBP) was -1.9% in the youngest, 0.6% in the middle-aged,
      and 8.2% in the oldest subjects. Increasing handgrip strength was associated with
      an increase in SBP and cSBP (1.08 and 1.37 mmHg per 1 kg increase in handgrip
      strength, respectively, P=0.01). Finally, PWV was significantly associated with
      increasing handgrip strength with an increase of 0.05 m/s per 1 kg higher
      handgrip strength (P=0.01). Conclusion: This study found increased blood pressure
      levels after isometric challenge and a strong association between handgrip
      strength and change in blood pressure levels and aortic stiffness in elderly
      subjects.

PMID- 29662307
TI  - Thyroid nodules in centenarians: prevalence and relationship to lifestyle
      characteristics and dietary habits.
AB  - Background: Thyroid nodules (TNs) are common thyroid lesions in older population.
      Few studies have focused on the prevalence of TNs and their relationship to
      lifestyle characteristics and dietary habits in centenarians. The current study
      aimed at determining the prevalence of TNs in Chinese centenarians by using high
      resolution ultrasound (US) equipment and at investigating its relationship to
      lifestyle characteristics and dietary habits. Participants and methods: The
      current study was part of the China Hainan Centenarian Cohort Study that was
      conducted in Hainan, an iodine-sufficient region in People's Republic of China. A
      total of 874 permanent residents aged >=100 years (mean age =102.8+/-2.8 years)
      without any missing data were included in the analysis. Results: Among the
      participants, 649 of them were detected at least one TN under the US
      examinations. The overall prevalence rate of TNs was 74.3%. The prevalence of TNs
      was higher in participants who were women, had hypertension, had diabetes, and
      were underweight compared with their counterparts. Multivariate logistic
      regression analyses showed that being female, hypertensive, and diabetic; betel
      quid consumption; and red meat consumption were independent risk factors, while
      being underweight and nut consumption were independent protective factors for
      TNs. Conclusion: Our findings indicate that the presence of TNs was highly
      prevalent in Chinese centenarians, particularly in women. In addition to gender,
      having hypertension, having diabetes, and being underweight, the presence of TNs
      was independently associated with betel quid, red meat, and nut consumption.
      Further prospective studies are warranted to verify these associations in
      populations from different age strata, races, cultures, and iodine
      supplementation.

PMID- 29662308
TI  - Hypoglycemic and antioxidant effect of Tai chi exercise training in older adults
      with metabolic syndrome.
AB  - Introduction: The antioxidant and anti-inflammatory effects of Tai chi (TC)
      exercise training in healthy older adults has been demonstrated. However, there
      are no studies on this effect in older adults with metabolic syndrome (MetS).
      Purpose: The aim of this study was to determine the effect of TC exercise on
      oxidative stress and inflammatory markers in older adults with MetS. Methods: A
      quasi-experimental study was carried out with a sample of 110 older sedentary
      volunteers with clinical diagnoses of MetS: (i) a control group, n = 50, of
      individuals who do not participate in physical exercise, of which 37 fulfilled
      the entire study protocol, and (ii) an experimental group, n = 60, of subjects
      enrolled in a TC exercise training program (eight-form easy), 5 days a week for 6
      months, in sessions of 50 min, under the supervision of a qualified instructor,
      of which 48 fulfilled the entire study protocol. We measured in both groups (pre-
      and post-intervention) the following cardiovascular parameters: resting heart
      rate (RHR), diastolic and systolic blood pressure (DBP and SBP), mean arterial
      pressure (MAP), RHR-SBP product, RHR-MAP product; glycosylated hemoglobin
      (HbA1c); oxidative stress markers (superoxide dismutase, total antioxidant
      status, thiobarbituric acid reacting substances, and oxidative stress score); and
      inflammation markers (TNF-alpha, IL-6, IL-8, and IL-10). Results: A statistically
      significant decrease in HbA1c concentration was observed in the TC group compared
      with the control group (p < 0.05). This group also showed a statistically
      significant increase in TAS and a decrease in the oxidative stress score (p <
      0.05). We did not observe changes in the cardiovascular parameters (RHR, DBP,
      SBP, MAP, RHR-SBP product, and RHR-MAP product) in the TC experimental group
      compared to the control group. Conclusion: Our findings suggest that the practice
      of TC exercise has an antioxidative and hypoglycemic effect in the elderly with
      MetS.

PMID- 29662309
TI  - Description of nighttime cough epochs in patients with stable COPD GOLD II-IV.
AB  - Purpose: Chronic cough is one of the main symptoms of COPD. Ambulatory objective
      monitoring provides novel insights into the determinants and characteristics of
      nighttime cough in COPD. Materials and methods: Nighttime cough was monitored
      objectively by LEOSound lung sound monitor in patients with stable COPD II-IV. In
      30 patients, with 10 patients in each stage group, nighttime cough was analyzed
      for epoch frequency, epoch severity (epoch length and coughs per epoch), and
      pattern (productive or nonproductive). Results: Cough was found in all patients
      ranging from 1 to 294 events over the recording period. In 29 patients, cough
      epochs were monitored, ranging from 1 to 75 epochs. The highest amount of cough
      epochs was found in patients with COPD stage III. Active smokers had
      significantly more productive cough epochs (61%) than nonsmokers (24%).
      Conclusion: We found a high rate of nighttime cough epochs in patients with COPD,
      especially in those in stage III. Productive cough was predominantly found in
      patients with persistent smoking. LEOSound lung sound monitor offers a practical
      and valuable opportunity to evaluate cough objectively.

PMID- 29662310
TI  - In vitro/vivo drug release and anti-diabetic cardiomyopathy properties of
      curcumin/PBLG-PEG-PBLG nanoparticles.
AB  - Background: The objective of this study was to survey the therapeutic function of
      curcumin-encapsulated poly(gamma-benzyl l-glutamate)-poly(ethylene glycol)
      poly(gammabenzyl l-glutamate) (PBLG-PEG-PBLG) (P) on diabetic cardiomyopathy
      (DCM) via cross regulation effect of calcium-sensing receptor (CaSR) and
      endogenous cystathionine-gamma-lyase (CSE)/hydrogen sulfide (H2S). Methods:
      Diabetic rats were preconditioned with 20 mg/kg curcumin or curcumin/P complex
      continuously for 8 weeks. The blood and myocardiums were collected, the level of
      serum H2S was observed, and the [Ca2+]i content was measured in myocardial cells,
      and hematoxylin-eosin, CaSR, CSE, and calmodulin (CaM) expression were detected.
      Results: Both curcumin and curcumin/P pretreatment alleviated pathological
      morphological damage of myocardium, increased H2S and [Ca2+]i levels, and
      upregulated the expression of CaSR, CSE, and CaM as compared to DCM group, while
      curcumin/P remarkably augmented this effect. Conclusion: PBLG-PEG-PBLG could
      improve water-solubility and bioactivity of curcumin and curcumin/PBLG-PEG-PBLG
      significantly alleviated diabetic cardiomyopathy.

PMID- 29662311
TI  - The 95RGD97 sequence on the Aalpha chain of fibrinogen is essential for binding
      to its erythrocyte receptor.
AB  - Background: Erythrocyte aggregation, a cardiovascular risk factor, is increased
      by high plasma fibrinogen levels. Here, the effect of different fibrinogen
      mutations on binding to its human erythrocyte receptor was assessed in order to
      identify the interaction sites. Methods: Three fibrinogen variants were tested,
      specifically mutated in their putative integrin recognition sites on the Aalpha
      chain (mutants D97E, D574E and D97E/D574E) and compared with wild-type
      fibrinogen. Results: Atomic force microscopy-based force spectroscopy
      measurements showed a significant decrease both on the fibrinogen-erythrocyte
      binding force and on its frequency for fibrinogen with the D97E mutation,
      indicating that the corresponding arginine-glycine-aspartate sequence (residues
      95-97) is involved in this interaction, and supporting that the fibrinogen
      receptor on erythrocytes has a beta3 subunit. Changes in the fibrin clot network
      structure obtained with the D97E mutant were observed by scanning electron
      microscopy. Conclusion: These findings may lead to innovative perspectives on the
      development of new therapeutic approaches to overcome the risks of fibrinogen
      driven erythrocyte hyperaggregation.

PMID- 29662312
TI  - Nanoselenium prevents eimeriosis-induced inflammation and regulates mucin gene
      expression in mice jejunum.
AB  - Background: Although elemental selenium has been found to be effective against
      Eimeria, no study has yet investigated the effects of selenium nanoparticles
      (SeNPs) on the Eimeria parasite. The aim of this study, therefore, was to
      evaluate the ameliorative effect of SeNPs compared with elemental selenium on
      mice jejunum infected with sporulated oocysts of Eimeria papillata. Methods: The
      mice were divided into 4 groups, with the first being the non-infected, control
      group, and the second, third, and fourth groups being orally inoculated with
      1,000 sporulated oocysts of E. papillata. The third and fourth groups also
      received, respectively, an oral dose of 0.1 mg/kg sodium selenite and 0.5 mg/kg
      SeNPs daily for 5 consecutive days. Results: The infection induced severe
      histopathological jejunal damage, reflected in the form of destroyed jejunal
      mucosa, increased jejunal oxidative damage, a reduction in the number of jejunal
      goblet cells, and increased production of pro-inflammatory cytokines, quantified
      by real-time polymerase chain reaction. Treatment of mice with SeNPs
      significantly decreased the oocyst output in the feces by ~80%. Furthermore, the
      number of parasitic stages counted in stained jejunal paraffin sections was
      significantly decreased after the mice were treated with SeNPs. In addition, the
      number of goblet cells increased from 42.6+/-7.3 to 95.3+/-8.5 cells/10 villus
      crypt units after treatment. By day 5 post-infection with E. papillata, SeNPs
      could be seen to have significantly increased the activity of glutathione
      peroxidase from 263+/-10 to 402.4+/-9 mU/mL. Finally, SeNPs were able to regulate
      the gene expression of mucin 2, interleukin 1beta, interleukin 6, interferon
      gamma, and tumor necrosis factor alpha in the jejunum of mice infected with E.
      papillata. Conclusion: The results collectively showed that SeNPs are more
      effective than sodium selenite with regard to their anti-coccidial, anti-oxidant,
      and anti-inflammatory role against eimeriosis induced in the jejunum of mice.

PMID- 29662313
TI  - Inhibition of H1N1 influenza virus-induced apoptosis by functionalized selenium
      nanoparticles with amantadine through ROS-mediated AKT signaling pathways.
AB  - Introduction: As a therapeutic antiviral agent, the clinical application of
      amantadine (AM) is limited by the emergence of drug-resistant viruses. To
      overcome the drug-resistant viruses and meet the growing demand of clinical
      diagnosis, the use of biological nanoparticles (NPs) has increased in order to
      develop novel anti-influenza drugs. The antiviral activity of selenium NPs with
      low toxicity and excellent activities has attracted increasing attention for
      biomedical intervention in recent years. Methods and results: In the present
      study, surface decoration of selenium NPs by AM (Se@AM) was designed to reverse
      drug resistance caused by influenza virus infection. Se@ AM with less toxicity
      remarkably inhibited the ability of H1N1 influenza to infect host cells through
      suppression of the neuraminidase activity. Moreover, Se@AM could prevent H1N1
      from infecting Madin Darby Canine Kidney cell line and causing cell apoptosis
      supported by DNA fragmentation and chromatin condensation. Furthermore, Se@AM
      obviously inhibited the generation of reactive oxygen species and activation of
      phosphorylation of AKT. Conclusion: These results demonstrate that Se@AM is a
      potentially efficient antiviral pharmaceutical agent for H1N1 influenza virus.

PMID- 29662314
TI  - Pretreatment of daily teriparatide enhances the increase of bone mineral density
      in cortical bones by denosumab therapy.
AB  - Background: While it is well known that teriparatide (TPTD) increases bone
      mineral density (BMD) in osteoporotic patients, it is unknown whether TPTD
      pretreatment affects BMD after denosumab (DMAb) therapy. Methods: Fifty-seven
      patients in TPTD-pretreated group and 35 patients in DMAb-alone group had been
      further analyzed, all of whom were treated by DMAb for 1.5 years. Vitamin D (400
      IU) and Ca (600 mg) supplementation was used in all patients. The BMD of lumbar 1
      4 vertebrae (L-BMD), bilateral total hips (H-BMD), and bilateral femoral neck (FN
      BMD) was quantified at first visit, and at 4, 8, 12, and 18 months after daily
      TPTD treatment following four times DMAb treatment. Results: There were
      significant differences in L-BMD (p=0.004) and H-BMD (p=0.026) at baseline
      between TPTD-pretreated and DMAb-alone groups, although there was no significant
      difference in FN-BMD between the two groups. The increase of L-BMD by DMAb
      therapy was less in TPTD-pretreated group than in DMAb-alone group. There was no
      significant difference in H-BMD, although percent changes of H-BMD tended to be
      higher in the TPTD-pretreated group than those in the DMAb-alone group. Percent
      change in FN-BMD at 4 months (p=0.067) and 12 months (p=0.057) tended to be
      higher in TPTD-pretreated group than in DMAb-alone group. Percent change in FN
      BMD at 18 months was significantly higher in TPTD-pretreated group (p=0.004) than
      in DMAb-alone group. Conclusion: These findings suggest that the pretreatment of
      TPTD might have enhanced the increase of BMD in cortical bones treated by DMAb.
      Thus, it is favorable that TPTD can be used for osteoporotic patients who have
      high fracture risks with cortical bones.

PMID- 29662315
TI  - Pitfalls in the ankle-brachial index and brachial-ankle pulse wave velocity.
AB  - Background: The ankle-brachial index (ABI) and pulse wave velocity (PWV) are
      indices of atherosclerosis and arterial stiffness. The Japan-made measuring
      devices of those indices have spread widely because of their convenience and the
      significance of the parameters. However, studies that comprehensively discuss the
      various pitfalls in using these indices are not available. Methods: This study
      presents several representative pitfalls in using the ABI and brachial-ankle PWV
      (baPWV) by showing the result sheets of the device, "the Vascular Profiler".
      Furthermore, some considerations when utilizing these indices in the future are
      also discussed. Results: Several diseases such as arteriosclerosis obliterans
      (ASO), arterial calcification in the lower limb, arterial stenosis in the right
      upper-limb, aortic valve diseases, arterial stenosis in the upper-limb of the
      contralateral side of the hemodialysis access, are the representative pitfalls
      when evaluating ABI and baPWV. Moreover, a measurement error is found to actually
      exist. Furthermore, same phenomena are considered most likely to occur when using
      other similar indices and devices. Conclusion: The ABI and baPWV are the useful
      and significant biomarkers. Nevertheless, caution is sometimes necessary when
      interpreting them. Moreover, rigorous patient exclusion criteria should be
      considered when using those indices in the severely conditioned patient
      population. And the results of this study can be applied to enhance the literacy
      using other indices, such as the cardio-ankle vascular index and other similar
      devices.

PMID- 29662316
TI  - Metformin inhibits proliferation and cytotoxicity and induces apoptosis via AMPK
      pathway in CD19-chimeric antigen receptor-modified T cells.
AB  - Background: CD19-chimericantigen receptor (CAR) modified T cells (CD19-CAR T
      cells) have been well documented to possess potent anti-tumor properties against
      CD19-expressingleukemia cells. As a traditional medicine, metformin has been
      widely used to treat type II diabetes mellitus and more recently has become a
      candidate for the treatment of cancer. However, no report has revealed the direct
      effect of metformin on CD19-CAR T cell biological function and its underling
      mechanisms. Purpose: The purpose of this research was to explore the effect of
      metformin on CD19-CAR T cell biological function and the mechanisms involved.
      Methods: CD19-CAR T cells proliferation, apoptosis and cytotoxicity were mainly
      tested by CCK-8 assay, flow cytometry and ELISA. The detection of mechanism
      primarily used western blot. Bioluminescence imaging is the main application
      technology of animal studies. Results: In the current study, it was found that
      metformin inhibited CD19-CAR T cell proliferation and cytotoxicity and induced
      apoptosis. Furthermore, our study revealed that metformin activated AMPK and
      suppressed mTOR and HIF1alpha expression. By using an AMPK inhibitor, compound C,
      we demonstrated the crucial roles of AMPK in CD19-CAR T cells when they were
      treated with metformin. Finally, we verified that metformin suppressed the
      cytotoxicity of CD19-CAR T cell in vivo. Conclusion: Taken together, these
      results indicated that metformin may play an important role in modulating CD19
      CAR T cell biological functions in an AMPK-dependent and mTOR/HIF1alpha
      independent manner.

PMID- 29662317
TI  - Association between WWOX and the risk of malignant tumor, especially among
      Asians: evidence from a meta-analysis.
AB  - Purpose: Many studies have been carried out to examine whether there are
      associations between WWOX polymorphisms (rs3764340 C>G, rs12918952 G>A, and
      rs383362 G>T) and malignant tumor risk, but the results from these studies
      remained inconsistent and even controversial. In the present study, we performed
      a meta-analysis to evaluate the relationships comprehensively. Methods: Published
      reports were searched in PubMed, Google Scholar, and Chinese National Knowledge
      Infrastructure databases. Eight eligible case-control studies were included in
      the final analysis. In the analysis, pooled odds ratios (ORs) with corresponding
      95% CIs were calculated in five genetic models to assess the genetic risk.
      Egger's regression and Begg's funnel plots test were conducted to appraise the
      publication bias. Results: We found that rs12918952 G>A and rs383362 G>T
      polymorphisms were not associated with the susceptibility of malignant tumor.
      However, a significant correlation was found between WWOX rs3764340 C>G and
      malignant tumor risk in three genetic models (CG vs CC: OR=1.31, 95% CI: 1.12
      1.53, P=0.031; GG/CG vs CC: OR=1.31, 95% CI: 1.11-1.54, P=0.014; G vs C: OR=1.28,
      95% CI: 1.09-1.50, P=0.009). Furthermore, when stratified by source of control,
      the results were significant especially in population-based control for
      rs3764340. Conclusion: In general, our results first indicated that the rs3764340
      C>G polymorphism in WWOX gene can increase the susceptibility of tumor, while the
      others cannot. However, large, well-designed epidemiological studies are required
      to verify our findings.

PMID- 29662318
TI  - Rare malignant insulinoma with multiple liver metastases derived from ectopic
      pancreas: 3-year follow-up and literature review.
AB  - Here, we report the diagnosis and treatment of a very rare case of malignant
      insulinoma derived from ectopic pancreas. A middle-aged woman presented with a 6
      year history of recurrent hypoglycemia with multiple lesions in liver. Admission
      workup revealed elevated serum insulin and C-peptide, as well as multiple lesions
      in the liver (largest being 4.3 cm), enlarged lymph nodes around the pancreas,
      and a lesion (of 3.5 cm) at the proximal jejunum, as shown by contrast computed
      tomography (CT). Liver biopsy showed the lesions to be well-differentiated
      neuroendocrine tumors, grade G1. 68Gallium-exendin-4 positron emission
      tomography/CT confirmed the origin as the lesion located at the jejunum. The
      combination treatment of everolimus plus long-acting octreotide relieved symptoms
      and achieved a partial tumor response. Maintenance treatment of the somatostatin
      analog (ie, octreotide) alone was administered. Three years of follow-up, up to
      the writing of this report, showed good survival, with the patient remaining
      asymptomatic and euglycemic without disease progression. This case shows that
      68Gallium-exendin-4 positron emission tomography/CT is useful for locating
      insulinoma, especially for insulinoma derived from ectopic pancreas, and that
      everolimus plus octreotide with maintenance somatostatin analog alone is an
      effective drug strategy for treating inoperable malignant insulinoma.

PMID- 29662319
TI  - Clinicopathological characteristics and prognostic value of the cancer stem cell
      marker ALDH1 in ovarian cancer: a meta-analysis.
AB  - Background: The clinicopathological and prognostic values of the cancer stem cell
      marker aldehyde dehydrogenase 1 (ALDH1) in ovarian cancer (OC) remain unknown.
      The aim of our meta-analysis was to evaluate ALDH1's association with
      clinicopathological characteristics and its prognostic significance in patients
      with OC. Materials and methods: PubMed, Embase, and China Biology Medicine were
      systematically searched for eligible studies (up to October 2017). Pooled odds
      ratios (ORs) or hazard ratios (HRs) with 95% CIs were used to evaluate the
      association of ALDH1 expression with clinicopathological features and survival
      outcomes. Results: A total of 17 papers (18 studies) that included 2,531 patients
      with OC were analyzed. The results showed a significant association between
      increasing ALDH1 expression and International Federation of Gynecology and
      Obstetrics stage (OR 2.02, 95% CI 1.16-3.52), lymph node metastasis (OR 1.91, 95%
      CI 1.01-3.61), and distant metastasis (OR 5.43, 95% CI 1.44-20.42) in OC.
      However, no significant correlation was found between increasing ALDH1 expression
      and age (OR 0.90, 95% CI 0.25-3.28), tumor size (OR 1.13, 95% CI 0.75-1.71),
      tumor location (OR 0.69, 95% CI 0.22-2.13), ascite status (OR 0.74, 95% CI 0.49
      1.11), resistance status (OR 0.70, 95% CI 0.14-3.51), or clinicopathological type
      (OR 1.14, 95% CI 0.69-1.86). Moreover, a high ALDH1 expression was significantly
      associated with overall survival (HR 1.56, 95% CI 1.21-2.02) but not with disease
      free survival (HR 1.38, 95% CI 0.99-1.93). Conclusion: The meta-analysis
      indicates that increasing ALDH1 predicts poor prognosis and clinicopathological
      characteristics in OC. Future studies are needed to explore tailored treatments
      that directly target ALDH1 for the improvement of survival in OC.

PMID- 29662320
TI  - Omalizumab for severe asthma: toward personalized treatment based on biomarker
      profile and clinical history.
AB  - Asthma is a heterogeneous syndrome with numerous underlining molecular and
      inflammatory mechanisms contributing to the wide spectrum of clinical phenotypes.
      Multiple therapies targeting severe asthma with type 2 (T2) high inflammation are
      or soon will be available. T2 high inflammation is defined as inflammation
      associated with atopy or eosinophilia or an increase in cytokines associated with
      T-helper 2 lymphocytes. Omalizumab is a humanized anti-IgE monoclonal antibody
      and the first biologic therapy approved for moderate-severe allergic asthma.
      Despite the specificity of biologic therapies like omalizumab, clinical response
      is variable, with approximately 50% of treated patients achieving the primary
      outcome. A prior identification of the ideal candidate for therapy would improve
      patient outcomes and optimize the use of health care resources. As the number of
      biologic therapies for asthma increases, the goal is identification of biomarkers
      or clinical phenotypes likely to respond to a specific therapy. This review
      focuses on potential biomarkers and clinical history that may identify responders
      to omalizumab therapy for asthma.

PMID- 29662321
TI  - Serum hepatitis B core antibody levels predict HBeAg seroconversion in chronic
      hepatitis B patients with high viral load treated with nucleos(t)ide analogs.
AB  - Background: Patients with chronic hepatitis B virus (HBV) infection who are
      hepatitis B virus e antigen (HBeAg) positive are increasingly being treated with
      nucleos(t)ide analogs (NUCs). However, the predictive value of serum hepatitis B
      virus core antibody (HBcAb) levels for HBeAg seroconversion among patients with
      high viral load remains unclear. Methods: This study consisted of 74 patients
      with high viral load (HBV DNA >1 * 107 copies/mL) enrolled in a multicenter,
      randomized, controlled trial, treated with lamivudine and adefovir (N = 32) or
      entecavir (N = 42) for up to 96 weeks. Serum HBV DNA, quantitative hepatitis B
      virus surface antigen (HBsAg), HBeAg, and HBeAb was tested at each visit.
      Quantitative HBcAb evaluation was conducted for all the available samples in the
      trial, by using a newly developed double-sandwich anti-HBc immunoassay. Results:
      Serum HBcAb levels were significantly higher in patients with a serum alanine
      aminotransferase (ALT) level more than five times the upper limit of normal (ULN)
      compared with patients with ALT levels within 5 * ULN (4.25 +/- 0.61 vs. 3.94 +/-
      0.47 log10 IU/mL, P = 0.0345). Patients with HBeAg seroconversion were associated
      with a higher level of HBcAb at baseline, compared with those without HBeAg
      seroconversion (4.38 +/- 0.54 vs. 4.02 +/- 0.58 log10 IU/mL, P = 0.029). The area
      under receiver operating characteristic curve of baseline HBcAb for HBeAg
      seroconversion was 0.71 (95% CI: 0.55-0.86, P = 0.013). When the baseline HBcAb
      level was >4.375 log10 IU/mL, the sensitivity and specificity to predict HBeAg
      seroconversion at week 96 were 62.5% and 74.2%, and the positive likelihood ratio
      (LR) and negative LR were 2.42 and 0.51, respectively. The multivariate analysis
      result indicated that baseline serum HBcAb level was the only independent
      predictor for HBeAg seroconversion at week 96, with an odds ratio of 4.78.
      Conclusion: Baseline serum HBcAb level >4.375 log10 IU/mL could satisfactorily
      predict HBeAg seroconversion among patients with high viral load treated with
      NUC.

PMID- 29662322
TI  - A comparative trial of ice application versus EMLA cream in alleviation of pain
      during botulinum toxin injections for palmar hyperhidrosis.
AB  - Background: Botulinum toxin is a safe and effective therapy for palmar
      hyperhidrosis, but the associated pain from injections limits the usefulness of
      this method of treatment. Purpose: To evaluate the efficacy of Eutectic Mixture
      of Local Anesthetics (EMLA) cream versus ice application in alleviation of pain
      during botulinum toxin injections for palmar hyperhidrosis. Methods: In this
      prospective study, 23 patients underwent palm Botox injections to treat their
      excessive sweating. In each patient, EMLA cream was applied to one palm and ice
      was applied directly before the injections in the other palm. Pain was evaluated
      using a Visual Analog Scale. Results: Statistically, there was a significant
      difference in pain control between EMLA cream group and ice application group
      (p<0.05). The average pain score on the hands where EMLA cream was applied was
      8.9 (SD=0.81), whereas it was 4.8 (+/-0.9) in the ice group. Conclusion: In this
      study, the successful use of ice application in reducing pain by 40% in
      comparison to EMLA cream during Botox toxin injection for palmar hyperhidrosis is
      demonstrated.

PMID- 29662323
TI  - Investigation of chronic efficacy and safety profile of two potential anti
      inflammatory bipyrazole-based compounds in experimental animals.
AB  - Purpose: Although nonsteroidal anti-inflammatory drugs are widely used to treat a
      variety of disorders, their administration is associated with gastrointestinal
      side effects, acute kidney injury and liver enzymes' elevation. Accordingly,
      researchers are encouraged to create novel agents with better safety profile. The
      aim of the current study was to evaluate the chronic efficacy and safety profile
      of two compounds previously proven to have acceptable acute anti-inflammatory and
      analgesic activities. Materials and methods: Doses were determined through
      formalin-induced mice paw edema-based dose-response curves. Granuloma weight was
      used to assess the chronic effect of the investigated compounds as compared to
      the vehicle and diclofenac representing the positive and the negative controls,
      respectively. Mice kidneys, livers and stomachs were histologically examined.
      Moreover, troponin I, alanine aminotransferase, aspartate aminotransferase, serum
      creatinine and blood urea nitrogen levels were measured. Results: The results
      highlight that the granulomas and exudates developed in mice after 7 days of
      treatment, with compound I and compound II were significantly lower than that of
      the negative control group. Moreover, compound I showed significantly better anti
      inflammatory effect than diclofenac. Troponin level was undetected in all groups.
      Histopathological examination of the stomach revealed normal mucosa for both
      tested compounds and controls. Likewise, kidneys showed neither significant
      histologic alteration nor biomarkers increase as compared to the control over
      both 7- and 30-day treatment periods. Mice that received the tested compounds or
      diclofenac exhibited transient liver damage specifically; congestion,
      vacuolization, necrosis and inflammation after 7 days of treatment which
      decreased significantly after 30 days of treatment as emphasized by the Suzuki
      score and biomarker levels. Conclusion: Since the tested compounds, specifically
      compound I, presented a satisfactory chronic safety profile as well as anti
      inflammatory effect, it is worth conducting further molecular pharmacological,
      toxicological and bioavailability studies to elucidate the efficacy of these
      potential anti-inflammatory bipyrazole compounds.

PMID- 29662324
TI  - Clinical and molecular genetic features of Hb H and AE Bart's diseases in central
      Thai children.
AB  - Background: alpha-Thalassemia, one of the major thalassemia types in Thailand, is
      caused by either deletion or non-deletional mutation of one or both alpha-globin
      genes. Inactivation of three alpha-globin genes causes hemoglobin H (Hb H)
      disease, and the combination of Hb H disease with heterozygous hemoglobin E (Hb
      E) results in AE Bart's disease. Objective: This study aimed to characterize the
      clinical and hematological manifestations of 76 pediatric patients with Hb H and
      AE Bart's diseases treated at Phramongkutklao Hospital, a tertiary care center
      for thalassemia patients in central Thailand. Patients and methods: Seventy-six
      unrelated pediatric patients, 58 patients with Hb H disease and 18 patients with
      AE Bart's disease, were enrolled in this study. Their clinical presentations,
      transfusion requirement, laboratory findings, and mutation analysis were
      retrospectively reviewed and analyzed. Results: A total of 76 pediatric patients
      with Hb H and AE Bart's diseases who mainly lived in central Thailand were
      included in this study. The clinical severities of patients with non-deletional
      mutations were more severe than those with deletional mutations. Eighty-six
      percent of patients with non-deletional AE Bart's disease required more blood
      transfusion compared to 12.5% of patients with deletional AE Bart's disease. Non
      deletional AE Bart's disease also had a history of urgent blood transfusion with
      the average of 6+/-0.9 times compared to 1+/-0.3 times in patients with
      deletional Hb H disease. The difference was statistically significant.
      Conclusion: This study revealed the differences in clinical spectrum between
      patients with Hb H disease and those with AE Bart's disease in central Thailand.
      The differentiation of alpha-thalassemia is essential for appropriate management
      of patients. The molecular diagnosis is useful for diagnostic confirmation and
      genotype-phenotype correlation.

PMID- 29662325
TI  - Sonic hedgehog signaling in spinal cord contributes to morphine-induced
      hyperalgesia and tolerance through upregulating brain-derived neurotrophic factor
      expression.
AB  - Purpose: Preventing opioid-induced hyperalgesia and tolerance continues to be a
      major clinical challenge, and the underlying mechanisms of hyperalgesia and
      tolerance remain elusive. Here, we investigated the role of sonic hedgehog (Shh)
      signaling in opioid-induced hyperalgesia and tolerance. Methods: Shh signaling
      expression, behavioral changes, and neurochemical alterations induced by morphine
      were analyzed in male adult CD-1 mice with repeated administration of morphine.
      To investigate the contribution of Shh to morphine-induced hyperalgesia (MIH) and
      tolerance, Shh signaling inhibitor cyclopamine and Shh small interfering RNA
      (siRNA) were used. To explore the mechanisms of Shh signaling in MIH and
      tolerance, brain-derived neurotrophic factor (BDNF) inhibitor K252 and anti-BDNF
      antibody were used. Results: Repeated administration of morphine produced obvious
      hyperalgesia and tolerance. The behavioral changes were correlated with the
      upregulation and activation of morphine treatment-induced Shh signaling.
      Pharmacologic and genetic inhibition of Shh signaling significantly delayed the
      generation of MIH and tolerance and associated neurochemical changes. Chronic
      morphine administration also induced upregulation of BDNF. Inhibiting BDNF
      effectively delayed the generation of MIH and tolerance. The upregulation of BDNF
      induced by morphine was significantly suppressed by inhibiting Shh signaling. In
      naive mice, exogenous activation of Shh signaling caused a rapid increase of BDNF
      expression, as well as thermal hyperalgesia. Inhibiting BDNF significantly
      suppressed smoothened agonist-induced hyperalgesia. Conclusion: These findings
      suggest that Shh signaling may be a critical mediator for MIH and tolerance by
      regulating BDNF expression. Inhibiting Shh signaling, especially during the early
      phase, may effectively delay or suppress MIH and tolerance.

PMID- 29662326
TI  - CD133 Promotes Adhesion to the Ovarian Cancer Metastatic Niche.
AB  - Cancer stem cells (CSCs) are an attractive therapeutic target due to their
      predicted role in both metastasis and chemoresistance. One of the most commonly
      agreed on markers for ovarian CSCs is the cell surface protein CD133. CD133+
      ovarian CSCs have increased tumorigenicity, resistance to chemotherapy, and
      increased metastasis. Therefore, we were interested in defining how CD133 is
      regulated and whether it has a role in tumor metastasis. Previously we found that
      overexpression of the transcription factor, ARID3B, increased the expression of
      PROM1 (CD133 gene) in ovarian cancer cells in vitro and in xenograft tumors. We
      report that ARID3B directly regulates PROM1 expression. Importantly, in a
      xenograft mouse model of ovarian cancer, knockdown of PROM1 in cells expressing
      exogenous ARID3B resulted in increased survival time compared with cells
      expressing ARID3B and a control short hairpin RNA. This indicated that ARID3B
      regulation of PROM1 is critical for tumor growth. Moreover, we hypothesized that
      CD133 may affect metastatic spread. Given that the peritoneal mesothelium is a
      major site of ovarian cancer metastasis, we explored the role of PROM1 in
      mesothelial attachment. PROM1 expression increased adhesion to mesothelium in
      vitro and ex vivo. Collectively, our work demonstrates that ARID3B regulates
      PROM1 adhesion to the ovarian cancer metastatic niche.

PMID- 29662327
TI  - Spotlight on dabrafenib/trametinib in the treatment of non-small-cell lung
      cancer: place in therapy.
AB  - Advanced non-small-cell lung cancer (NSCLC) remains a challenging disease. The
      limited utility of chemotherapy indicates the need for additional therapeutic
      options. Targeted therapy continues to be an important tool in the treatment of
      NSCLC. Mutations within the RAS-RAF-MEK-MAPK pathway, specifically the BRAF V600E
      mutation, have become an important target for the subset of NSCLC patients with
      this mutation. This paper summarizes the clinical evidence that lead to the
      recent approval of the combination of dabrafenib and trametinib to treat patients
      with advanced NSCLC who harbor a BRAF V600E mutation.

PMID- 29662328
TI  - Hyporeninemic hypoaldosteronism in a patient with diabetes mellitus: an
      unforgettable case report.
AB  - A 58-year-old man presented with a 3-year history of chronic and intermittent
      hyperkalemia requiring recurrent attendances to the emergency department for
      urgent treatment. His medical history included secondary diabetes mellitus
      following a bout of acute pancreatitis and a previous splenectomy for a
      spontaneous splenic rupture. He also had a history of prolonged use of non
      steroidal anti-inflammatory drugs for back pain and painful neuropathy. He was
      not on any medication or diet that would cause a raised serum potassium level and
      his renal function was normal. He was on a basal-bolus insulin regimen but his
      diabetes control had been poor for several years. As the hyperkalemia had gone on
      for so long in the presence of normal renal function, he went on to have further
      tests. Adrenal insufficiency had been ruled out following a short Synacthen test.
      Further investigations revealed low serum aldosterone levels and inappropriately
      low serum renin levels in the presence of hyperkalemia. This was suggestive of
      hyporeninemic hypoaldosteronism (HH). He was then treated with fludrocortisone
      and furosemide and his serum potassium levels remained normal. Additionally, he
      did not require any more emergency admissions to treat hyperkalemia thereafter.
      It was concluded that the HH-induced hyperkalemia was caused by diabetes mellitus
      or due to a combination of diabetes and prolonged use of non-steroidal anti
      inflammatory drugs. The absence of renal impairment may have contributed to the
      delay in diagnosis. HH is a commonly overlooked cause of hyperkalemia. This case
      highlights the fact that it should always be suspected when unexplained
      hyperkalemia is found in patients with only mild-moderately impaired renal
      function, especially in the presence of diabetes mellitus.

PMID- 29662329
TI  - Diagnosis and staging of fibrosis in patients with chronic hepatitis C:
      comparison and critical overview of current strategies.
AB  - In the past years, what has always been considered undisputed true in liver
      fibrosis staging has been challenged. Diagnostic performance of histological
      evaluation has proven to be significantly influenced by sample- and observer
      related variabilities. Differentiation between lower levels of fibrosis remains
      difficult for many, if not all, test modalities, including liver biopsy but,
      perhaps, such a distinction is not indispensable in light of current therapeutic
      approaches. Biomarkers and elastography offer, nonetheless, high predictive
      values for advanced fibrosis and cirrhosis and correlate well with liver-related
      outcomes. Necroinflammation, steatosis, and hemodynamic changes may significantly
      interfere with elastography-based techniques, and longitudinal follow-up
      strategies must be tailored in light of these findings. Knowledge of different
      test modalities and diagnostic performance indicators can allow for better
      clinical decision-making and resource allocation.

PMID- 29662330
TI  - Development and validation of MyLifeTracker: a routine outcome measure for youth
      mental health.
AB  - Purpose: Routine outcome measures are now being designed for session-by-session
      use, with emphasis on clinically meaningful items and sensitivity to change.
      Despite an increasing mental health service focus for young people aged 12-25
      years, there is a lack of outcome measures that are designed to be used across
      this age group. Consequently, MyLifeTracker (MLT) was developed as a brief mental
      health outcome measure designed for young people for routine use. It consists of
      the following five items targeting areas of importance to young people: general
      well-being, day-to-day activities, relationships with friends, relationships with
      family, and general coping. Participants and methods: The measure was tested with
      75,893 young people aged 12-25 years attending headspace centers across Australia
      for mental health-related issues. Results: MLT showed a robust unidimensional
      factor structure and appropriate reliability. It exhibited good concurrent
      validity against well-validated measures of psychological distress, well-being,
      functioning, and life satisfaction. The measure was further demonstrated to be
      sensitive to change. Conclusion: MLT provides a psychometrically sound mental
      health outcome measure for young people. The measure taps into items that are
      meaningful to young people and provides an additional clinical support tool for
      clinicians and clients during therapy. The measure is brief and easy to use and
      has been incorporated into an electronic system that routinely tracks session-by
      session change and produces time-series charts for the ease of use and
      interpretation.

PMID- 29662331
TI  - Psychosocial distress and the preferred method of delivery of mind-body
      interventions among patients with head-and-neck cancer.
AB  - Objective: To describe the psychosocial distress of head-and-neck cancer patients
      at the completion of therapy and the interest in and the preferred method of
      delivery of mind-body interventions (MBIs) among head-and-neck cancer patients.
      Materials and methods: A descriptive, cross-sectional design was used to measure
      sleep disturbance, depression, anxiety, and the interest in and the preference
      for MBIs using anonymous, self-report questionnaires among a convenience sample
      of 30 males at their 3-month follow-up. Questionnaires included the Pittsburgh
      Sleep Quality Index, Hospital Anxiety and Depression Scale, and the self-created
      Survey for Preferred Methods of MBI. Frequency distributions and descriptive
      statistics were used to describe the sample demographic and clinical
      characteristics. Results: The mean age of the sample was 59 years. Oral cancer
      (63%) was the most common type of cancer. Nineteen participants (63%, 90% CI 47%
      78%) had some interest in MBIs. Of interested participants, 8 (42%) preferred
      participating in MBIs alone, 10 (53%) preferred participating in MBIs at homes,
      10 (53%) preferred participating in MBIs using a computer or mobile device, and 8
      (42%) preferred participating in MBIs after the diagnosis, but before treatment
      started. Mean depression, anxiety, and sleep disturbance scores were 8.25 (SD
      2.93), 5.41 (SD 3.52), and 6.3 (SD 3.86), respectively. Results from the
      independent-samples t-test and Mann-Whitney U tests revealed no significant
      differences in anxiety, depression, and sleep disturbance by MBI interest.
      Conclusion: Asking about depression, anxiety, and sleep disturbances may help to
      identify head-and-neck cancer patients at risk for psychosocial distress. These
      findings suggest an interest in MBIs, but further research is warranted.

PMID- 29662332
TI  - Corrigendum.
AB  - [This corrects the article DOI: 10.1177/1179552217711430.].

PMID- 29662333
TI  - The Prevalence of Hypovitaminosis D and Its Associated Risk Factors Among Women
      of Reproductive Age in Saudi Arabia: A Systematic Review and Meta-Analysis.
AB  - Vitamin D deficiency is currently a worldwide epidemic. Middle Eastern countries,
      including Saudi Arabia, have high vitamin D deficiency prevalence, most
      prominently among women, despite their plentiful year-round sunshine. Previous
      research investigating vitamin D status among Saudi women of reproductive age (15
      49 years) is scarce, and no study has used a nationally representative sample, so
      this review quantified overall hypovitaminosis D prevalence among women in Saudi
      Arabia and explored the associated risk factors. The Web of Science, Scopus, and
      Medline databases were searched for prior studies in Saudi Arabia exploring
      vitamin D status among women of reproductive age, published between January 1,
      2000 and May 25, 2017. Data were extracted from the identified studies, and a
      random effects model meta-analysis established the overall hypovitaminosis D
      prevalence. The initial search yielded 223 possibly relevant articles; 13 were
      confirmed as eligible, with samples totaling 2877 women aged between 15 and 49
      years. Meta-analysis revealed a mean serum 25-hydroxyvitamin D, 25(OH)D, level of
      13.1 ng/mL (95% confidence interval [CI]: 11.6-14.6) and an overall prevalence of
      hypovitaminosis D, defined as 25(OH)D < 30 ng/mL, of 77.4% (95% CI: 63.2-87.3),
      mostly due to insufficient sunlight exposure and low dietary vitamin D intake.
      There is therefore a need for a national strategy to raise vitamin D levels among
      women in Saudi Arabia by advising them on natural vitamin D sources, and
      recommending the timing and duration of sun exposure, while also defining a
      national approach to vitamin D fortification and supplementation.

PMID- 29662334
TI  - Continuum modelling of segregating tridisperse granular chute flow.
AB  - Segregation and mixing of size multidisperse granular materials remain
      challenging problems in many industrial applications. In this paper, we apply a
      continuum-based model that captures the effects of segregation, diffusion and
      advection for size tridisperse granular flow in quasi-two-dimensional chute flow.
      The model uses the kinematics of the flow and other physical parameters such as
      the diffusion coefficient and the percolation length scale, quantities that can
      be determined directly from experiment, simulation or theory and that are not
      arbitrarily adjustable. The predictions from the model are consistent with
      experimentally validated discrete element method (DEM) simulations over a wide
      range of flow conditions and particle sizes. The degree of segregation depends on
      the Peclet number, Pe, defined as the ratio of the segregation rate to the
      diffusion rate, the relative segregation strength kappaij between particle
      species i and j, and a characteristic length L, which is determined by the
      strength of segregation between smallest and largest particles. A parametric
      study of particle size, kappaij , Pe and L demonstrates how particle segregation
      patterns depend on the interplay of advection, segregation and diffusion.
      Finally, the segregation pattern is also affected by the velocity profile and the
      degree of basal slip at the chute surface. The model is applicable to different
      flow geometries, and should be easily adapted to segregation driven by other
      particle properties such as density and shape.

PMID- 29662335
TI  - Vibration of carbon nanotubes with defects: order reduction methods.
AB  - Order reduction methods are widely used to reduce computational effort when
      calculating the impact of defects on the vibrational properties of nearly
      periodic structures in engineering applications, such as a gas-turbine bladed
      disc. However, despite obvious similarities these techniques have not yet been
      adapted for use in analysing atomic structures with inevitable defects. Two order
      reduction techniques, modal domain analysis and modified modal domain analysis,
      are successfully used in this paper to examine the changes in vibrational
      frequencies, mode shapes and mode localization caused by defects in carbon
      nanotubes. The defects considered are isotope defects and Stone-Wales defects,
      though the methods described can be extended to other defects.

PMID- 29662336
TI  - Random distributions of initial porosity trigger regular necking patterns at high
      strain rates.
AB  - At high strain rates, the fragmentation of expanding structures of ductile
      materials, in general, starts by the localization of plastic deformation in
      multiple necks. Two distinct mechanisms have been proposed to explain multiple
      necking and fragmentation process in ductile materials. One view is that the
      necking pattern is related to the distribution of material properties and
      defects. The second view is that it is due to the activation of specific
      instability modes of the structure. Following this, we investigate the emergence
      of necking patterns in porous ductile bars subjected to dynamic stretching at
      strain rates varying from 103 s-1 to 0.5*105 s-1 using finite-element
      calculations and linear stability analysis. In the calculations, the initial
      porosity (representative of the material defects) varies randomly along the bar.
      The computations revealed that, while the random distribution of initial porosity
      triggers the necking pattern, it barely affects the average neck spacing,
      especially, at higher strain rates. The average neck spacings obtained from the
      calculations are in close agreement with the predictions of the linear stability
      analysis. Our results also reveal that the necking pattern does not begin when
      the Considere condition is reached but is significantly delayed due to the
      stabilizing effect of inertia.

PMID- 29662337
TI  - Localization in semi-infinite herringbone waveguides.
AB  - The paper includes novel results for the scattering and localization of a time
      harmonic flexural wave by a semi-infinite herringbone waveguide of rigid pins
      embedded within an elastic Kirchhoff plate. The analytical model takes into
      account the orientation and spacing of the constituent parts of the herringbone
      system, and incorporates dipole approximations for the case of closely spaced
      pins. Illustrative examples are provided, together with the predictive
      theoretical analysis of the localized waveforms.

PMID- 29662338
TI  - Effects of geometric nonlinearity in an adhered microbeam for measuring the work
      of adhesion.
AB  - Design against adhesion in microelectromechanical devices is predicated on the
      ability to quantify this phenomenon in microsystems. Previous research related
      the work of adhesion for an adhered microbeam to the beam's unadhered length, and
      as such, interferometric techniques were developed to measure that length. We
      propose a new vibration-based technique that can be easily implemented with
      existing atomic force microscopy tools or similar metrology systems. To make such
      a technique feasible, we analysed a model of the adhered microbeam using the
      nonlinear beam theory put forth by Woinowsky-Krieger. We found a new relation
      between the work of adhesion and the unadhered length; this relation is more
      accurate than the one by Mastrangelo & Hsu (Mastrangelo & Hsu 1993 J.
      Microelectromech. S., 2, 44-55. (doi:10.1109/84.232594)) which is commonly used.
      Then, we derived a closed-form approximate relationship between the microbeam's
      natural frequency and its unadhered length. Results obtained from this analytical
      formulation are in good agreement with numerical results from three-dimensional
      nonlinear finite-element analysis.

PMID- 29662339
TI  - Nonlinear dynamics of a dispersive anisotropic Kuramoto-Sivashinsky equation in
      two space dimensions.
AB  - A Kuramoto-Sivashinsky equation in two space dimensions arising in thin film
      flows is considered on doubly periodic domains. In the absence of dispersive
      effects, this anisotropic equation admits chaotic solutions for sufficiently
      large length scales with fully two-dimensional profiles; the one-dimensional
      dynamics observed for thin domains are structurally unstable as the transverse
      length increases. We find that, independent of the domain size, the
      characteristic length scale of the profiles in the streamwise direction is about
      10 space units, with that in the transverse direction being approximately three
      times larger. Numerical computations in the chaotic regime provide an estimate
      for the radius of the absorbing ball in [Formula: see text] in terms of the
      length scales, from which we conclude that the system possesses a finite energy
      density. We show the property of equipartition of energy among the low Fourier
      modes, and report the disappearance of the inertial range when solution profiles
      are two-dimensional. Consideration of the high-frequency modes allows us to
      compute an estimate for the analytic extensibility of solutions in [Formula: see
      text]. We also examine the addition of a physically derived third-order
      dispersion to the problem; this has a destabilizing effect, in the sense of
      reducing analyticity and increasing amplitude of solutions. However, sufficiently
      large dispersion may regularize the spatio-temporal chaos to travelling waves. We
      focus on dispersion where chaotic dynamics persist, and study its effect on the
      interfacial structures, absorbing ball and properties of the power spectrum.

PMID- 29662340
TI  - On the theory of drainage area for regular and non-regular points.
AB  - The drainage area is an important, non-local property of a landscape, which
      controls surface and subsurface hydrological fluxes. Its role in numerous
      ecohydrological and geomorphological applications has given rise to several
      numerical methods for its computation. However, its theoretical analysis has
      lagged behind. Only recently, an analytical definition for the specific catchment
      area was proposed (Gallant & Hutchinson. 2011 Water Resour. Res.47, W05535.
      (doi:10.1029/2009WR008540)), with the derivation of a differential equation whose
      validity is limited to regular points of the watershed. Here, we show that such a
      differential equation can be derived from a continuity equation (Chen et al. 2014
      Geomorphology219, 68-86. (doi:10.1016/j.geomorph.2014.04.037)) and extend the
      theory to critical and singular points both by applying Gauss's theorem and by
      means of a dynamical systems approach to define basins of attraction of local
      surface minima. Simple analytical examples as well as applications to more
      complex topographic surfaces are examined. The theoretical description of
      topographic features and properties, such as the drainage area, channel lines and
      watershed divides, can be broadly adopted to develop and test the numerical
      algorithms currently used in digital terrain analysis for the computation of the
      drainage area, as well as for the theoretical analysis of landscape evolution and
      stability.

PMID- 29662341
TI  - Small nanoparticles, surface geometry and contact forces.
AB  - In this molecular dynamics study, we examine the local surface geometric effects
      of the normal impact force between two approximately spherical nanoparticles that
      collide in a vacuum. Three types of surface geometries-(i) crystal facets, (ii)
      sharp edges, and (iii) amorphous surfaces of small nanoparticles with radii R<10
      nm-are considered. The impact forces are compared with their macroscopic
      counterparts described by nonlinear contact forces based on Hertz contact
      mechanics. In our simulations, edge and amorphous surface contacts with weak
      surface energy reveal that the average impact forces are in excellent agreement
      with the Hertz contact force. On the other hand, facet collisions show a linearly
      increasing force with increasing compression. Our results suggest that the nearly
      spherical nanoparticles are likely to enable some nonlinear dynamic phenomena,
      such as breathers and solitary waves observed in granular materials, both
      originating from the nonlinear contact force.

PMID- 29662342
TI  - A canonical form of the equation of motion of linear dynamical systems.
AB  - The equation of motion of a discrete linear system has the form of a second-order
      ordinary differential equation with three real and square coefficient matrices.
      It is shown that, for almost all linear systems, such an equation can always be
      converted by an invertible transformation into a canonical form specified by two
      diagonal coefficient matrices associated with the generalized acceleration and
      displacement. This canonical form of the equation of motion is unique up to an
      equivalence class for non-defective systems. As an important by-product, a damped
      linear system that possesses three symmetric and positive definite coefficients
      can always be recast as an undamped and decoupled system.

PMID- 29662343
TI  - Post-buckling of a pressured biopolymer spherical shell with the mode
      interaction.
AB  - Imperfection sensitivity is essential for mechanical behaviour of biopolymer
      shells characterized by high geometric heterogeneity. The present work studies
      initial post-buckling and imperfection sensitivity of a pressured biopolymer
      spherical shell based on non-axisymmetric buckling modes and associated mode
      interaction. Our results indicate that for biopolymer spherical shells with
      moderate radius-to-thickness ratio (say, less than 30) and smaller effective
      bending thickness (say, less than 0.2 times average shell thickness), the
      imperfection sensitivity predicted based on the axisymmetric mode without the
      mode interaction is close to the present results based on non-axisymmetric modes
      with the mode interaction with a small (typically, less than 10%) relative
      errors. However, for biopolymer spherical shells with larger effective bending
      thickness, the maximum load an imperfect shell can sustain predicted by the
      present non-axisymmetric analysis can be significantly (typically, around 30%)
      lower than those predicted based on the axisymmetric mode without the mode
      interaction. In such cases, a more accurate non-axisymmetric analysis with the
      mode interaction, as given in the present work, is required for imperfection
      sensitivity of pressured buckling of biopolymer spherical shells. Finally, the
      implications of the present study to two specific types of biopolymer spherical
      shells (viral capsids and ultrasound contrast agents) are discussed.

PMID- 29662345
TI  - Stochastic isotropic hyperelastic materials: constitutive calibration and model
      selection.
AB  - Biological and synthetic materials often exhibit intrinsic variability in their
      elastic responses under large strains, owing to microstructural inhomogeneity or
      when elastic data are extracted from viscoelastic mechanical tests. For these
      materials, although hyperelastic models calibrated to mean data are useful,
      stochastic representations accounting also for data dispersion carry extra
      information about the variability of material properties found in practical
      applications. We combine finite elasticity and information theories to construct
      homogeneous isotropic hyperelastic models with random field parameters calibrated
      to discrete mean values and standard deviations of either the stress-strain
      function or the nonlinear shear modulus, which is a function of the deformation,
      estimated from experimental tests. These quantities can take on different values,
      corresponding to possible outcomes of the experiments. As multiple models can be
      derived that adequately represent the observed phenomena, we apply Occam's razor
      by providing an explicit criterion for model selection based on Bayesian
      statistics. We then employ this criterion to select a model among competing
      models calibrated to experimental data for rubber and brain tissue under single
      or multiaxial loads.

PMID- 29662347
TI  - Reviewers in 2017.

PMID- 29662344
TI  - Manipulating nanoparticle transport within blood flow through external forces: an
      exemplar of mechanics in nanomedicine.
AB  - A large number of nanoparticles (NPs) have been raised for diverse biomedical
      applications and some of them have shown great potential in treatment and imaging
      of diseases. Design of NPs is essential for delivery efficacy due to a number of
      biophysical barriers, which prevents the circulation of NPs in vascular flow and
      their accumulation at tumour sites. The physiochemical properties of NPs, so
      called '4S' parameters, such as size, shape, stiffness and surface
      functionalization, play crucial roles in their life journey to be delivered to
      tumour sites. NPs can be modified in various ways to extend their blood
      circulation time and avoid their clearance by phagocytosis, and efficiently
      diffuse into tumour cells. However, it is difficult to overcome these barriers
      simultaneously by a simple combination of '4S' parameters for NPs. At this
      moment, external triggerings are necessary to guide the movement of NPs, which
      include light, ultrasound, magnetic field, electrical field and chemical
      interaction. The delivery system can be constructed to be sensitive to these
      external stimuli which can reduce the non-specific toxicity and improve the
      efficacy of the drug-delivery system. From a mechanics point of view, we discuss
      how different forces play their roles in the margination of NPs in blood flow and
      tumour microvasculature.

PMID- 29662346
TI  - DC dynamic pull-in instability of a dielectric elastomer balloon: an energy-based
      approach.
AB  - This paper reports an energy-based method for the dynamic pull-in instability
      analysis of a spherical dielectric elastomer (DE) balloon subjected to a quasi
      statically applied inflation pressure and a Heaviside step voltage across the
      balloon wall. The proposed technique relies on establishing the energy balance at
      the point of maximum stretch in an oscillation cycle, followed by the imposition
      of an instability condition for extracting the threshold parameters. The material
      models of the Ogden family are employed for describing the hyperelasticity of the
      balloon. The accuracy of the critical dynamic pull-in parameters is established
      by examining the saddle-node bifurcation in the transient response of the balloon
      obtained by integrating numerically the equation of motion, derived using the
      Euler-Lagrange equation. The parametric study brings out the effect of inflation
      pressure on the onset of the pull-in instability in the DE balloon. A
      quantitative comparison between the static and dynamic pull-in parameters at four
      different levels of the inflation pressure is presented. The results indicate
      that the dynamic pull-in instability gets triggered at electric fields that are
      lower than those corresponding to the static instability. The results of the
      present investigation can find potential use in the design and development of the
      balloon actuators subjected to transient loading. The method developed is
      versatile and can be used in the dynamic instability analysis of other
      conservative systems of interest.

PMID- 29662348
TI  - Cadmium-induced testicular damage in a rat model of subchronic intoxication.
AB  - Background: Cadmium (Cd)-induced testicular damage in relation to spermatogenesis
      has not been well studied. We studied the mechanism of Cd-induced testicular
      damage in a rat model of subchronic intoxication. Methods:  Male Sprague-Dawley
      rats were subcutaneously injected with 0.6 mg Cd/kg per day for 6 weeks. The
      concentration of Cd in urine, serum and testes was measured by using atomic
      absorption spectrophotometry. Testicular damage was evaluated by counting the
      spermatogonia (SG) and spermatocytes (SC) on one cut-surface of five seminiferous
      tubules in stages VII or VIII of spermatogenesis every week. The location of
      intratesticular cadmium was determined by using oxine-fluorescent cytochemistry.
      Results: There were no differences in the testes/bodyweight ratio between the
      study and control groups. The concentration of Cd in the testes increased more
      than 100-fold that in serum after week 2, suggesting active testicular Cd
      accumulation (1-3 mg/g tissue). Cadmium accumulation was detected in SG and SC.
      The number of SG and SC diminished significantly in the study group (week 2: SG
      74%, SC 90%; week 4: SG 47%, SC 75%; week 6: SG 30%, SC 54% of the control,
      respectively). Conclusions: Cadmium accumulated in SG and SC, consequently
      reduced the number of these cells, and disturbed the spermatogenesis in this rat
      model of subchronic Cd intoxication. Therefore, the number of SG decreased in
      this rat model of subchronic Cd intoxication. (Reprod Med Biol 2002; 1: 59-63).

PMID- 29662349
TI  - Bilateral tubal pregnancies after the termination of intrauterine pregnancy
      following gamete intrafallopian transfer.
AB  - It is well known that the prevalence of heterotopic pregnancies following
      assisted reproductive technology (ART) is much higher than among spontaneous
      pregnancies. Here, we illustrate a very rare case of bilateral simultaneous tubal
      pregnancies combined with intrauterine pregnancy (incomplete abortion) following
      gamete intrafallopian transfer (GIFT). In this case, unsuspected bilateral tubal
      pregnancies were diagnosed when laparotomy was performed 10 days after the
      termination of an intrauterine pregnancy. We conclude that a careful monitoring
      after the termination of an intrauterine pregnancy should be performed when the
      patient has prolonged genital bleeding, which might be a warning signal of
      heterotopic pregnancy existence even in patients without any risk factors of
      ectopic pregnancy. (Reprod Med Biol 2002; 1: 65-67).

PMID- 29662350
TI  - Role of transient hyperprolactinemia in the late follicular phase of the
      gonadotropin-stimulated cycle.
AB  - Background: Serum prolactin (PRL) concentration is known to transiently increase
      in rats; however, its change is obscure and the role of it is also unclear in
      women. We studied the relationship between estradiol (E2) and PRL production and
      the role of transient hyperprolactinemia in the late follicular phase of the
      gonadotropin-stimulated cycle. Methods: (1) Serum E2 and PRL concentrations were
      measured on an early follicular day and immediately before a human chorionic
      gonadotropin (hCG) injection in 60 patients with normoprolactinemia. Twelve of
      the 60 patients also received a gonadotropin injection with bromocriptine, and
      serum hormone levels were compared with those without bromocriptine. (2)
      Preovulatory serum E2 and PRL concentrations were compared between the natural
      and clomiphene treatment cycles in 14 hormonally normal women. (3) Changes of
      serum PRL concentrations were measured before and after E2 loading in five
      premature ovarian failure (POF) patients. (4) The E2 production by granulosa
      cells in the presence of PRL was measured. Results and Conclusion: Serum E2 and
      PRL concentrations were significantly increased by the gonadotropin injection.
      Bromocriptine treatment completely inhibited the PRL increase, but further
      increased serum E2 concentration on the late follicular day. The E2 loading
      increased serum PRL levels in POF patients. The clomiphene treatment increased
      serum E2 but decreased PRL concentrations. Prolactin significantly decreased E2
      production by granulosa cells. A feedback loop may exist between E2 and PRL to
      control the excess E2 production induced by gonadotropin injection. (Reprod Med
      Biol 2002; 1: 69-74).

PMID- 29662351
TI  - Testosterone induces activation of porcine primordial follicles in vitro.
AB  - Purpose: The mechanism underlying primordial follicle activation is poorly
      understood. In this study, in-vitro culture and subsequent xenotransplantation
      were conducted to determine whether testosterone promotes the activation of
      porcine primordial follicles. Methods: Prepubertal porcine ovarian cortical
      strips containing primordial follicles were cultured in the presence of
      testosterone for 7 days, and subsequently transplanted to immunodeficient mice
      for 2 months. After culture and transplantation, development of follicles was
      examined histologically. The presence of androgen receptors in oocytes was
      assessed by use of western blot and immunohistochemical analyses. Results:
      Testosterone at 10-6 m induced the primordial follicle transition to the
      intermediate (19 +/- 4%) and primary (3 +/- 1%) stages after 7-day culture, while
      56 +/- 5% of primordial follicles remained in the initial pool. Higher
      concentrations, above 10-5 m, or lower concentrations, below 10-6 m, did not
      induce follicle transition to the primary stage. After 7-day culture with 10-6 m
      testosterone, ovarian cortical strips were transplanted to immunodeficient mice.
      Some of the follicles developed to the secondary (15 +/- 3%) and antral (10 +/-
      3%) stages, whereas 44 +/- 7% of primordial follicles remained in the initial
      pool. In the culture experiment, estradiol-17beta (10-7-10-5 m) had no
      significant effect on follicle activation. The androgen receptor antagonist,
      cyproterone acetate, inhibited the stimulatory effect of testosterone on
      primordial follicle activation, suggesting an androgen receptor-mediated action
      of testosterone. Western blot and immunohistochemical analyses revealed that
      androgen receptors were present in the oocytes of primordial follicles.
      Conclusions: These results suggest that testosterone at 10-6 m promotes the
      activation of porcine primordial follicles in vitro through the androgen
      receptors in the oocytes.

PMID- 29662352
TI  - Size of the perivitelline space and incidence of polyspermy in rabbit and hamster
      oocytes.
AB  - Purpose: The size of the perivitelline space and the incidence of polyspermy were
      observed in ovulated and cultured oocytes from rabbits and hamsters with or
      without treatment by 4-methylumbelliferone (MU), an inhibitor of hyaluronic acid
      (HA) synthase, in order to examine the relationship between the incidence of
      polyspermy and the size of the perivitelline space. The amount of HA in the
      medium with MU-treated hamster oocytes was measured and compared with that in the
      medium with untreated oocytes. Methods: The perivitelline space of oocytes with
      1st polar bodies was measured by use of a micrometer under a microscope, and the
      incidence of polyspermy was observed in the oocytes after insemination. The
      amount of HA in the medium was examined using an enzyme-linked immunosorbent
      assay. The distribution of cortical granules was observed by staining with FITC
      conjugated LCA. Results: In both rabbit and hamster, the mean size of the
      perivitelline space was significantly smaller and the incidence of polyspermy was
      significantly higher in the cultured and MU-treated oocytes than in the ovulated
      and untreated oocytes. The mean amount of HA in the medium with MU-treated
      oocytes (8.96 pg) was significantly smaller than that in the medium with
      untreated oocytes (21.77 pg). The distribution of cortical granules did not
      differ among the ovulated, cultured, and MU-treated oocytes. Conclusions: These
      findings suggest that the size of the perivitelline space is closely related to
      the incidence of polyspermy, and that the oocyte itself synthesizes and secretes
      the HA involved in the enlargement of the perivitelline space.

PMID- 29662353
TI  - One-step collagenase method for zona pellucida removal in unfertilized eggs: easy
      and gentle method for large-scale preparation.
AB  - Purpose: Zona pellucida (ZP)-free eggs are often used for studies such as
      evaluating the interaction of sperm-oolemma. To acquire ZP-free eggs, the most
      commonly used methods employ acidified Tyrode's solution, enzymatic digestion
      with a trypsin-like enzyme, or mechanical methods using micropipettes. However,
      acidified Tyrode's solution and trypsin-like enzymes often damage the oolemma,
      especially when many eggs are treated at once for mass sample analyses. The
      mechanical method requires skill, and it is time-consuming to prepare many ZP
      free eggs. Therefore, in this study, to establish an easy, reliable method for
      preparing ZP-free eggs, we examined the ZP digestion method originally reported
      by Zuccotti et al. (J Reprod Fertil 93:515-520, 1991) that uses collagenase.
      Methods: Mouse unfertilized eggs were treated with collagenase and acidified
      Tyrode's solution to compare the ZP-free rates, the effect on the oolemma, and
      the two-cell development rates of ZP-free eggs by in vitro fertilization. The
      effects on the oolemma were gauged by observing the polarity of the transmembrane
      protein localization of enhanced green fluorescence protein tagged CD9 protein
      (CD9-EGFP) and using differential interference contrast microscopy. Results:
      Collagenase removed the ZP and the cumulus cells from the cumulus oocyte complex.
      The collagenase method had no influence on the localization of CD9-EGFP,
      resulting in a high two-cell development rate. Additionally, the collagenase
      method could exclude low quality eggs with hardened ZP, since collagenase could
      not digest the hardened ZP. Conclusions: The one-step collagenase method is an
      easy preparation method for large numbers of high-quality ZP-free eggs.

PMID- 29662354
TI  - Unique bioactivities of bone morphogenetic proteins in regulation of reproductive
      endocrine functions.
AB  - Remarkable progress has been made in understanding the mechanism by which growth
      factors and oocytes can regulate the development and function of granulosa cells.
      Insufficiency of two oocyte-specific growth factors, growth differentiation
      factor-9 and bone morphogenetic protein (BMP)-15, cause female infertility.
      Expression of mRNA and/or protein for the BMP system components, including
      ligands, receptors and intracellular signal transduction factors, was
      demonstrated in cell components of growing preantral follicles, and biofunctional
      experiments have further revealed many important roles of the BMP system in
      regulation of reproductive function. In this review, recent advances in studies
      on biological actions of BMPs in ovarian folliculogenesis and in related
      endocrine tissues are discussed.

PMID- 29662355
TI  - Role of salsolinol in the regulation of pituitary prolactin and peripheral
      dopamine release.
AB  - (R)-Salsolinol (SAL), a dopamine (DA)-related tetrahydroisoquinoline, has been
      found in extracts of the neuro-intermediate lobes (NIL) of pituitary glands and
      in the median eminence of the hypothalamus obtained from intact male rats and
      from ovariectomized and lactating female rats. Moreover, analysis of SAL
      concentrations in NIL revealed parallel increases with plasma prolactin (PRL) in
      lactating rats exposed to a brief (10 min) suckling stimulus after 4-h
      separation. SAL is sufficiently potent in vivo to account for the massive
      discharge of PRL that occurs after physiological stimuli (i.e. suckling). At the
      same time, it was without effect on the secretion of other pituitary hormones. It
      has been also shown that another isoquinoline derivative, 1
      methyldihydroisoquinoline (1MeDIQ), which is a structural analogue of SAL, can
      dose-dependently inhibit the in-vivo PRL-releasing effect of SAL. Moreover,
      1MeDIQ can inhibit the elevation of plasma PRL induced by physiological stimuli,
      for example suckling, or in different stressful situations also. 1MeDIQ also has
      a psycho-stimulant action, which is fairly similar to the effect of amphetamine,
      i.e. it induces an increase in plasma catecholamine concentrations. It is clear
      from these data that this newly discovered endogenous compound could be involved
      in regulation of pituitary PRL secretion. It has also been observed that SAL is
      present in peripheral, sympathetically innervated organs, for example the atrium,
      spleen, liver, ovaries, vas deferens, and salivary gland. Furthermore, SAL
      treatment of rats results in dose-dependent and time-dependent depletion of the
      DA content of the organs listed above without having any effect on the
      concentration of norepinephrine. More importantly, this effect of SAL can be
      completely prevented by amphetamine and by 1MeDIQ pretreatment. It is clear there
      is a mutual interaction between SAL, 1MeDIQ, and amphetamine or alcohol, not only
      on PRL release; their interaction with catecholamine "synthesis/metabolism" of
      sympathetic nerve terminals is also obvious.

PMID- 29662356
TI  - Cancellation of in vitro fertilization treatment cycles predicts treatment
      outcome in female infertility patients aged 40 years or older.
AB  - Purpose: To investigate potential indicators of in vitro fertilization (IVF)
      treatment outcome for female infertility patients aged >= 40 years based on the
      clinical course. Methods: We retrospectively examined results of 111 female
      infertility patients aged >= 40 years undergoing IVF treatment. We investigated
      the relationship between treatment cycle cancellation and the final outcome of
      IVF treatment in female infertility patients aged >= 40 years. Results: A total
      of 44 pregnancies were achieved. Overall pregnancy rate per initiated treatment
      cycle was 12.1%, and 24 spontaneous abortions occurred (54.5%). No woman aged >=
      45 years achieved pregnancy. No patients conceived after 10 treatment cycles
      while 42 (11.5%) oocyte pick-up cycles and 120 (33.0%) embryo transfer cycles
      were canceled. Investigation of correlation with treatment cycle cancellation
      revealed that patients who experienced embryo transfer cancellation had a high
      spontaneous abortion rate while only a few patients who experienced oocyte pick
      up cancellation achieved pregnancy and even fewer achieved a successful outcome.
      Conclusions: Our study suggests that, in addition to patient age and number of
      treatment cycles, cancellation of treatment cycle also provides another useful
      indicator for pregnancy outcome.

PMID- 29662357
TI  - Histological and biological assessment of vitrified ovarian follicles from large
      animals.
AB  - Mammalian ovaries contain mixed populations of follicles at different
      developmental stages. A combination of vitrification and growth culture of
      ovarian follicles could provide the desired number of mature eggs from a
      preserved small amount of ovarian tissues. Secondary and primordial follicles
      from porcine and bovine ovaries were vitrified in solutions containing ethylene
      glycol, dimethyl sulfoxide and different concentrations of sucrose, and assessed
      via histological examination, viability staining, xenografting to immunodeficient
      mice, and in vitro culturing. Histological examination revealed the damage to
      oocytes and the damage to follicle components separately. The effects of sucrose
      in vitrification solutions on the follicles were different depending on the
      developmental stage of the follicle, oocyte size, cell type in the follicle, and
      species. Viability staining with fluorescein diacetate was useful to assess the
      damage to oocytes in secondary follicles. In the xenografts, vitrified bovine
      primordial and secondary follicles developed to the antral stage, and vitrified
      porcine primordial follicles developed to the secondary stage. Furthermore,
      bovine secondary follicles formed antrum-like structures in culture. These
      results suggest that histological examination and viability staining are valuable
      for assessing the direct effects of vitrification and warming conditions on
      follicles and oocytes, while xenografting and in vitro culturing can be useful
      for evaluating the developmental ability of vitrified follicles and oocytes.

PMID- 29662358
TI  - Mitochondrial biology in reproduction.
AB  - Mitochondrial biology plays an important role in the reproductive process, with
      influence on germ cell development and quality as well as embryonic development
      and reproductive success. This review outlines the role of mitochondrial genetics
      and function in reproductive biology, including a discussion of general
      mitochondrial function, genetics and germline transmission. Also highlighted are
      the mitochondrial morphologic changes that occur during oogenesis and the role
      these changes play in the mitochondrial bottleneck that influences the
      distribution of deleterious mitochondrial genomes to offspring. The review covers
      the influence of mitochondria in embryonic stem cell and induced pluripotent stem
      cell biology and development. Lastly, the role of mitochondrial biology in
      assisted reproductive techniques is discussed.

PMID- 29662359
TI  - Heterotopic autotransplantation of vitrified mouse ovary.
AB  - Purpose: The aim of this study was to investigate the survival and development of
      premature follicles and oocytes from a vitrified-transplanted ovary in a murine
      experimental model. Methods: The 14-day-old mice were unilaterally ovariectomized
      and the separated ovaries were vitrified by cryotop. After 2 weeks the ovaries
      were warmed and autotransplanted into the gluteus superfiscialis muscle. After 3
      weeks, these ovaries (vit-trans), the ovaries from the opposite side (OPP), and 7
      week fresh mouse ovaries as sham and control group (7 week-fresh), were recovered
      and examined histologically and by TUNEL test. Results: All 4 vitrified
      autotransplanted ovaries had developing follicles. Primordial, primary, preantral
      and antral follicles were found in all three groups (7 week-fresh, OPP and vit
      trans). The rate of apoptosis by TUNEL test was similar in all groups and no
      significant difference was found between vitrified-transplanted ovarian tissue
      and controls. Conclusions: These data demonstrate successful autotransplantation
      of vitrified whole mouse ovaries, manifested by the presence of all stages of
      folliculogenesis. According to the results of this experiment, heterotopic
      autotransplantation of whole cryopreserved ovary provides the opportunity for
      follicle development at all stages. However, further experiments are required to
      improve the efficiency of autotransplantation of cryopreserved ovaries to obtain
      better results.

PMID- 29662360
TI  - An immunohistochemical study of metroplastic surgical specimens from patients
      with a septate uterus.
AB  - Purpose: To elucidate the etiology of recurrent pregnancy loss in patients with
      congenital uterine anomalies, an immunohistochemical technique was used to
      quantitatively evaluate the vascular arrangement of septate uteri with respect to
      vascular density and morphology. Methods: Nine specimens obtained from patients
      who had undergone metroplastic surgery for the treatment of a septate uterus and
      10 control specimens from patients who had undergone a hysterectomy because of
      cervical carcinoma were used in this study. Formalin-fixed paraffin-embedded
      uterine specimens were then immunostained for CD34, which is specifically
      expressed in vascular endothelial cells. Results: The mean blood vessel count
      (mean +/- SD) for the myometrium was 149.7 +/- 22.7/field in the septate uteri
      and 162.2 +/- 36.4/field in the control uteri; these values were not
      significantly different. However, the total vessel cross-sectional areas, as
      evaluated quantitatively using the KS400 image analysis system, were 10350.4 +/-
      1024.3 MUm2/field for the septate uteri and 12002.9 +/- 2232.3 MUm2/field for the
      control uteri; these values were significantly different (p < 0.05). The vessel
      morphology expressed by vessel irregularity and deformity showed a characteristic
      change in the septate uterus. Conclusions: A significant difference in the
      distribution of the blood vessels existed between the septate and control uteri,
      presumably impairing blood flow in the myometrium and the adverse pregnancy
      outcome.

PMID- 29662361
TI  - Testicular volume discrepancy is associated with decreased semen quality in
      infertile Japanese males with varicoceles.
AB  - Purpose: We retrospectively reviewed infertile Japanese males for testicular
      volume discrepancies (D) and semen parameters to evaluate whether left grade II
      III varicoceles (V) cause testicular damage. Methods: Seventy-seven patients who
      had idiopathic male infertility and 88 who had V without other causes of
      infertility were examined. We excluded cases of azoospermia. Testicular volume
      was measured using a punched-out orchidometer. D was defined as a size difference
      of at least 3 ml. The frequency of D was compared between the patients with and
      without V. The semen parameters were reviewed in association with D and V.
      Results: The mean left and right testicular volumes were 19.4 and 20.1 ml,
      respectively (p < 0.001). D with a smaller left testis was more common in V+
      cases than in V- cases (26.1 vs. 13.0%, p = 0.0351). The sperm count and motility
      were also significantly lower (p = 0.0213 and p = 0.0217, respectively) in the D+
      patients with a smaller left testicular volume. Conclusions: In the patients with
      V, D was more common than in those without V. The semen parameters were worse if
      D was present in the patients with V. These results indicated that V could induce
      testicular atrophy and negatively affect semen quality. Therefore, the
      ipsilateral reduced testicular volume is considered to be a sign of persisting
      testicular damage by V.

PMID- 29662362
TI  - Psychological stress during in vitro fertilization and embryo transfer is
      influenced by the patients' background and gender.
AB  - Purpose: This study evaluated the changes in psychological stress during in vitro
      fertilization and embryo transfer (IVF-ET) and the relationship of such stress to
      the patients' background and gender. Methods: Sixty couples undergoing IVF-ET
      were administered the State-Trait Anxiety Inventory-JYZ (STAI) test at six
      different points during IVF-ET procedures. Anxiety scores at each time point were
      recorded and analyzed according to gender, fertility status, and duration of
      treatment. Results: The median state anxiety score for women increased following
      induction until oocyte collection, after which it temporarily declined and then
      increased again until the pregnancy test. No such changes were noted in men.
      Scores for women who had undergone a shorter period of IVF treatments were higher
      while state and trait anxiety in men increased with a prolonged treatment period.
      Unsuccessful treatment increased the state and trait anxiety of women.
      Conclusions: Psychological stress changed periodically depending on the duration
      of the patients' treatment and fertility status also influenced anxiety levels.
      These findings will prove helpful in guiding psychological therapy and counseling
      for couples attempting to conceive by in vitro fertilization.

PMID- 29662363
TI  - Isolated ACTH deficiency in self referred patients for LOH syndrome: two case
      reports.
AB  - We experienced two cases of isolated ACTH deficiency (IAD) in patients self
      referred for late-onset hypogonadism (LOH) syndrome. IAD is secondary adrenal
      insufficiency due to lack of secretion of ACTH and delayed diagnosis of this rare
      condition may be life-threatening. The predominant symptoms of IAD, such as
      general malaise and weakness, resemble those of LOH syndrome creating the
      possibility that IAD may be referred as LOH syndrome. Two middle aged men with
      severe general malaise visited our clinic requesting evaluation for LOH syndrome.
      Previous treatments had been ineffective and based on varying incorrect diagnoses
      by previous doctors. The patients self referred themselves for LOH syndrome. Some
      of their symptoms were consistent with LOH syndrome but others were atypical, in
      particular, the severity of malaise and appetite loss. Hormonal assays were
      compatible with adrenal insufficiency secondary to ACTH deficiency. Steroid
      replacement dramatically improved their symptoms. The clinical course of our two
      patients and points of differential diagnosis between IAD and LOH syndrome are
      reported here.

PMID- 29662364
TI  - Regulation of oocyte meiotic maturation by somatic cells.
AB  - In preovulatory follicles, each oocyte is surrounded by numerous layers of
      cumulus cells, forming the cumulus cell-oocyte complex. An LH surge induces
      meiotic resumption of the oocyte to progress to metaphase II. Because the
      expression of LH receptors is not detected in the oocyte and is minimal
      (negligible) in cumulus cells as compared with granulosa cells, secondary factors
      from granulosa cells are required to induce the ovulation process. One of the key
      factors secreted from granulosa cells is an EGF-like factor that activates the
      EGFR-ERK1/2 pathway in cumulus cells. The activated ERK1/2 pathway is not only
      involved in gene expression but also essential for the close of gap-junctional
      communication among cumulus cells and between cumulus cells and the oocyte.
      Closing gap-junctional communication decreases the amount of cGMP and/or cAMP to
      transfer into the oocyte, which requires activation of phosphodiesterase type III
      (PDE3) in the oocyte. PDE3 brakes down cAMP to decrease PKA activity in the
      oocyte. This decrease in PKA activity induces activation of CDK1 to resume
      meiosis from the germinal vesicle stage. Thus, the functions of cumulus cells
      that are regulated by granulosa cell-secreted factors are essential for oocyte
      meiotic resumption and maturation with developmental competence.

PMID- 29662365
TI  - Prevalence of cases of Mycoplasma hominis, Mycoplasma genitalium, Ureaplasma
      urealyticum and Chlamydia trachomatis in women with no gynecologic complaints.
AB  - Purpose: To evaluate the prevalence of Mycoplasma hominis, Mycoplasma genitalium,
      Ureaplasma urealyticum, Chlamydia trachomatis, Trichomonas vaginalis and
      Neisseria gonorrhoeae in women with no gynecologic complaints screened in the
      Human Reproduction outpatient clinic of Faculdade de Medicina of ABC, Brazil.
      Methods: A total of 106 women without gynecologic complaints and in reproductive
      age were evaluated. DNA was extracted from cells of the genitourinary tract with
      bacteria for the detection of six types of bacteria by polymerase chain reaction.
      Results: We found that 11.3 % of women had infection with M. hominis and 2.83 %
      for C. trachomatis. The other bacteria investigated occurred in 2.83 % of women.
      The percentage of infections identified was 15 %. Conclusion: The data showed a
      low percentage of women with genitourinary tract bacteria without symptoms.
      However, these infections can be sexually transmitted, and relate to infertility
      and other serious illnesses. The identification and treatment of infection in
      asymptomatic woman can avoid transmission and future genitourinary trait
      complications.

PMID- 29662366
TI  - What is the optimal condition for fertilization of IVM oocytes?
AB  - Application of in vitro maturation (IVM) is recently increasing for human
      infertility, especially to rescue patients of polycystic ovarian syndrome and
      ovarian hyperstimulation syndrome. To increase the application of IVM oocytes for
      embryo production and the efficiency of successful production of babies using IVM
      oocytes, quality control of oocytes and achievement of fertilization in the most
      suitable condition may be very important. In this paper, suitable conditions for
      fertilization of IVM oocytes will be discussed with recent knowledge about IVM
      and in vitro fertilization of oocytes in domestic animals. Currently, human
      oocytes are collected mainly from patients' ovaries 36 h following mild
      gonadotropin stimulation and used for IVM for 24-26 h. However, asynchronous
      progression of those oocytes to reach the metaphase-II stage may have occurred
      during the IVM culture. In the oocytes that have already progressed to the
      metaphase-II stage, sudden aging such as reduction in maturation promoting factor
      and MAP kinases will start to occur. Application of specific inhibitors of
      phosphodiesterase to control intracellular cAMP (cyclic adenosine monophosphate)
      level may be effective to synchronize timings of the germinal vesicle breakdown
      and consequently the meiotic progression of oocytes, and to improve the
      developmental competence. Furthermore, treatment of aging oocytes with caffeine
      appears to rescue them from reductions in maturation promoting factor and MAP
      kinases and to improve the developmental competence. Assessment methods to select
      oocytes with good quality may also be important to improve the successful rates.

PMID- 29662367
TI  - Hysteroscopic adhesiolysis for patients with Asherman's syndrome: menstrual and
      fertility outcomes.
AB  - Purpose: Most patients with Asherman's syndrome present with infertility and
      menstrual problems. In this retrospective clinical study, we analyzed patients
      with Asherman's syndrome who underwent hysteroscopic adhesiolysis to examine
      their associated symptoms, disease etiologies, and fertility outcomes. Methods:
      Twenty-seven patients with Asherman's syndrome that were diagnosed using
      hysteroscopy were recruited. The chief complaints were infertility,
      hypomenorrhea, and amenorrhea. Each case of Asherman's syndrome was classified
      according to the American Fertility Society classification. Hysteroscopic
      adhesiolysis was performed in all cases and concomitant transabdominal
      ultrasonography was conducted in cases with extensive and dense adhesions.
      Results: There were no complications associated with the hysteroscopic procedure.
      Normal menstrual cycles resumed in all cases. Of the 16 infertile patients, 9
      conceived. Three patients achieved term deliveries and one patient is currently
      pregnant. None of the patients had obstetric complications. Two patients had
      spontaneous abortions, one had an ectopic pregnancy, one had an abortion at 16
      weeks' gestation due to cervical incompetence, and one had a molar pregnancy and
      required uterine artery embolization for uncontrolled hemorrhaging during a
      dilatation and curettage procedure. Conclusions: Hysteroscopic adhesiolysis with
      transabdominal ultrasonography is a suitable treatment method for Asherman's
      syndrome. Subfertile patients with Asherman's syndrome undergoing adhesiolysis
      should be appropriately informed about the risk of associated life-threatening
      complications and preterm delivery.

PMID- 29662368
TI  - Observation of spermatozoa by a high-magnification microscope.
AB  - Semen analyses are the primary tool for evaluating male infertility, as semen
      parameters are useful for predicting potential fertility. In the field of
      assisted reproductive technology (ART), the single best motile spermatozoon
      should be selected, especially when performing intracytoplasmic sperm injection
      (ICSI). In this context, the motile sperm organelle morphology examination
      (MSOME) was developed as a method of assessing the detailed morphology of motile
      spermatozoa in real time at a magnification of up to 6,300* on a video system.
      The use of ICSI with MSOME-selected sperm is called intracytoplasmic
      morphologically selected sperm injection (IMSI). IMSI improves the outcomes of
      ICSI. MSOME can be also applied to evaluate male infertility. Among MSOME
      parameters, the presence of sperm nuclear vacuoles is the most important finding.
      Large sperm nuclear vacuoles (LNV) are related not only to poor ART outcomes, but
      also to poor semen quality and sperm DNA damage, such as DNA fragmentation and
      chromatin condensation failure. It has been suggested that sperm head vacuoles
      are produced at earlier stages of sperm maturation. It is possible that the
      number of LNV can be decreased by surgical or medical treatment for male
      infertility. Therefore, the level of LNV has the potential to be used as an
      alternative parameter of semen quality and a new tool for evaluating the
      therapeutic effects of treatment in male patients with infertility.

PMID- 29662369
TI  - Evaluation effects of allopurinol and FSH on reduction of ischemia-reperfusion
      injury and on preservation of follicle after heterotopic auto-transplantation of
      ovarian tissue in mouse.
AB  - Purpose: Allopurinol and FSH injection are applied to reduce ischemia-reperfusion
      injury and to increase survival rate for ovarian follicles after ovarian
      heterotopic autotransplantation in mice. Methods: Ovarian tissues from 6-week-old
      mice were grafted into back muscle then collected after 3 weeks. A total of five
      groups were included in this experiment as follows: control group (n = 5), sham
      operated group (n = 5), allopurinol treatment group (AP) (n = 5), follicle
      stimulating hormone (FSH) treatment group (n = 5), as well as, allopurinol and
      FSH treatment group (APF) (n = 5). We investigated survival, number and
      development of follicles, vaginal cytology along with plasma malondialdehyde
      (MDA) concentration in grafted ovary. Results: Total follicles count
      significantly increased in APF group compared with other treatment groups (p <
      0.05). MDA concentration significantly decreased in AP group and APF treatment
      group compared with sham-operated group. In AP group, vaginal smears showed
      presence of cornified epithelial cells three-five day after surgery. Conclusions:
      We demonstrated that allopurinol, as a XO inhibitor, plays an important role in
      order to decrease ischemia injury and to increase survival rate for follicles.
      Also, FSH, as a folliculogenesis and angiogenesis factor, increases development
      of follicles. It seems that allopurinol can cause re-establishing hypothalamus
      pituitary axis and finally can restore estrous cycle earlier than for the sham
      operated group, so it explains the increasing survival rate for follicles.

PMID- 29662370
TI  - Lysophosphatidic acid stimulates hyaluronan production by mouse cumulus-oocyte
      complexes.
AB  - Purpose: In mammals, cumulus expansion due to increased synthesis of hyaluronan
      was suggested to correlate with modification of the gap junction between cumulus
      cells and the oocyte, leading to cumulus expansion. We examined whether
      lysophosphatidic acid, a lipid mediator detected in mammalian body fluids,
      stimulates significant production of hyaluronan and thus affects mouse cumulus
      expansion in vitro. Methods: Cumulus-oocyte complexes isolated from the
      gonadotropin-treated ovaries of B6C3F1 mice were exposed to lysophosphatidic acid
      in the presence and absence of 0.3 % fetal bovine serum for measurement of
      cumulus expansion and released hyaluronan, respectively. Results: Exogenously
      added lysophosphatidic acid concentration-dependently stimulated production of
      hyaluronan in the cumulus cell-oocyte complex, and the stimulatory effect of
      lysophosphatidic acid on hyaluronan production was mediated through the signal
      pathways, including LPA receptor-Gi coupling, EGF receptor transactivation, and
      activations of phosphatidylinositol-specific phospholipase C, protein kinase C
      and mitogen-activated protein kinases. LPA increased mRNA expression of tumor
      necrosis alpha-induced protein 6, a hyaluronan-binding protein, and expansion of
      cumulus cell-oocyte complex. Conclusions: Lysophosphatidic acid in follicular
      fluids may participate in physiological cumulus expansion before ovulation by
      stimulating production of hyaluronan and proteins that enable the association of
      hyaluronan with cumulus cells and oocytes.

PMID- 29662371
TI  - Cryopreservation in ART and concerns with contamination during cryobanking.
AB  - The cryopreservation of gametes and embryos is vital to numerous fields of
      reproductive biology, including assisted human reproduction. With improved
      culture conditions, there are an increasing number of embryos to cryopreserve for
      potential use in subsequent cycles. Many of the gametes and embryos in human IVF
      are cryopreserved in open systems. Because liquid nitrogen is not sterile,
      concerns have been raised with regard to contamination from the liquid nitrogen
      and also cross-contamination between patients' germplasm. Human gamete and embryo
      cryopreservation are discussed, with recommendations on how to minimize and
      eliminate contamination, emphasizing the benefits of closed vitrification
      devices.

PMID- 29662372
TI  - Effect of single-oocyte culture system on in vitro maturation and developmental
      competence in mice.
AB  - Purpose: To investigate whether single-culture systems influence the quality of
      in vitro-matured oocytes, we examined the maturation and developmental competence
      of oocytes obtained by grouped in vitro maturation (IVM) or single IVM. Methods:
      In vitro-matured oocytes were obtained using the culture drop (CD) method for the
      grouped IVM experiments, and the CD and hanging drop (HD) method for the single
      IVM experiments. To evaluate oocyte developmental competence, we performed in
      vitro fertilization and culture, and counted the number of blastocysts. To
      evaluate the oocyte cytoplasmic maturation, we measured the maturation promoting
      factor (MPF) expression levels. Results: Oocytes cultured singly had lower
      maturity and developmental competence than the grouped IVM oocytes. However,
      enhanced oocyte fertility and blastocyst quality was achieved by the HD single
      IVM method. Additionally, the MPF activity level increased in all culture
      methods, compared to the control; however, it lagged behind nuclear maturation.
      Conclusions: These results suggest that the HD method is efficient for single
      IVM.

PMID- 29662373
TI  - Fertility preservation in men with cancer.
AB  - Due to recent advances in medical technologies, cancer has become more curable
      and chronic, and post-treatment quality of life, including male fertility, has
      become an important issue. Cancer itself can affect spermatogenesis through
      complex interactions, and cancer treatment such as surgery, radiotherapy and
      chemotherapy, all have certain detrimental effects on spermatogenesis. Currently,
      sperm cryopreservation before cancer treatment is the mainstay of fertility
      preservation, and is recommended by numerous guidelines. Although fertility
      preservation should be discussed with all cancer patients before treatment, it
      still remains underused. Postpubertal patients who are unable to bank sperm may
      undergo testicular sperm extraction before treatment. For prepubertal boys, there
      is no clinically established guideline for fertility preservation. Investigations
      such as spermatogonial stem cell culture are ongoing, and may lead to clinical
      options for fertility preservation in the future.

PMID- 29662374
TI  - Testicular sperm extraction with intracytoplasmic sperm injection for male
      infertility.
AB  - Background and Aims: Testicular sperm extraction (TESE) and intracytoplasmic
      sperm injection (ICSI) is an effective procedure for the treatment of male
      infertility, obstructive and non-obstructive azoospermia. We have reviewed our
      experience to investigate the correlation of TESE-ICSI with morphological,
      biophysical and endocrine profiles in 27 men. Results:  Testicular spermatozoa
      could be retrieved in 25 of 27 patients who underwent TESE. In two cases,
      testicular spermatozoa could not be recovered and their serum follicle
      stimulating hormone (FSH) levels were significantly higher than those of the
      former group. However, spermatozoa could be retrieved in sufficient numbers for
      ICSI, even in the patient with the highest FSH concentration. Johnsen scores
      evaluated by diagnostic pre-TESE open biopsies were significantly higher in the
      cases with viable testicular spermatozoa than those in the cases without
      spermatozoa. However, even in the patient whose Johnsen score was 2.1, testicular
      spermatozoa could be retrieved with TESE, and pregnancy was achieved by ICSI.
      Conclusions:  The serum FSH levels and the histological findings of the testes
      were strong predictors for successful TESE and provided useful information for
      consultation and making treatment decisions on an individual case. However,
      whether a patient has enough spermatozoa so that an IVF procedure with ICSI is
      possible can only be answered by a trial TESE. (Reprod Med Biol 2003; 2: 31-35).

PMID- 29662375
TI  - Endocrinological actions of Unkei-to, a herbal medicine, and its clinical
      usefulness in anovulatory and/or infertile women.
AB  - Kampo medicine (Chinese herbal medicine) has been reported to be effective in the
      treatment of pituitary-ovarian dysfunction in young women and in the treatment of
      undefined symptoms in perimenopausal women. It has been considered that both the
      diagnosis and treatment of ovulatory failure in adolescent girls or young women
      are necessary for the sake of future fertile capacity. However, treatment for the
      above patients is not easy as steroid hormones and strong stimulators of
      ovulation should not be recommended because of the several side-effects it
      causes. Furthermore, young women, especially teenagers, seem to be reluctant to
      visit gynecology clinics. A number of herbal medicines have been used for many
      centuries in China and Japan for the treatment of menstrual disorders and
      infertility. In general, the traditional Chinese herbal prescriptions are rather
      inexpensive and safe with little side-effects, and have properties for
      normalizing biological balances. Unkei-to is known to stimulate the synthesis and
      release of gonadotropins in the rat pituitary. In humans, Unkei-to is known to be
      effective in various menstrual disorders, abnormal uterine bleeding, and
      infertility. In the treatment of ovulatory failure, recent dynamic studies have
      revealed the mechanism by which Unkei-to stimulates the diencephalon-pituitary
      ovarian axis in humans. In this paper, we critically review the clinical data
      available (to date) in order to assess the efficacy of Unkei-to in inducing
      ovulation in several types of ovulatory disturbances. (Reprod Med Biol 2003; 2:
      45-61).

PMID- 29662376
TI  - Observation of pronuclei may not be an absolute indicator for fertilization in
      rescue intracytoplasmic sperm injection oocytes.
AB  - This case report describes a successful full-term pregnancy and birth after the
      transfer of rescue intracytoplasmic sperm injection (ICSI) embryos derived from 1
      day-old oocytes. A total of eight oocytes were retrieved and inseminated 3 h
      after collection. No oocytes were fertilized 16-18 h after insemination. A rescue
      ICSI was performed on the four metaphase II stage oocytes. At the regular time
      (16 h after ICSI) of examination for fertilization, there were no distinct two
      pronuclei (2PN) in the cytoplasm of any oocytes, but the culture of these oocytes
      led to the development of four two-cell stage embryos 26 h after ICSI. Further
      culture of these four embryos showed development to a four-cell stage the
      following day. The transfer of three embryos resulted in a full-term pregnancy
      with the delivery of a pair of healthy twins. This result suggests that the
      observation of 2PN at the normal time of fertilization assessment may not appear
      to be an absolute indicator of fertilization in the case of rescue ICSI. (Reprod
      Med Biol 2003; 2: 83-85).

PMID- 29662377
TI  - Identification of complexes of gelatinase A and tissue inhibitor of
      metalloproteinase-2 in human follicular fluid.
AB  - Background and Aims:  Ovulation involves considerable tissue remodeling in normal
      ovarian function. These processes are expected to involve matrix
      metalloproteinases (MMP). Follicular rupture is caused by the degradation of the
      basement membrane between the thecal and granulose layers, as well as disruption
      of the extracellular matrix (ECM) at the site of rupture. We report on the
      existence of the complexes of progelatinase A (proMMP-2), MMP-2 and a tissue
      inhibitor of metalloproteinase-2 (TIMP-2) using zymographic and immunological
      techniques in human follicular fluid (HFF). Methods and Results:  Partial
      purification of the complexes was achieved by using gelatin affinity column
      chromatography. The peak (tubes 68-73) in this chromatography showed gelatinase
      activities by gelatin-zymography, and also an inhibition by EDTA
      (metalloproteinase inhibitor). The molecular weights of the gelatinase activities
      were approximately 72 and 67 kDa, and were consistent with standard proMMP-2 and
      MMP-2, as found by using gelatin-zymography. Similarly, the band in this peak was
      consistent with standard recombinant full-length TIMP-2, as found by the use of
      western blot analysis, and the molecular weight of the band was approximately 21
      kDa. Conclusion:  As proMMP-2, MMP-2 and TIMP-2 exist in the peak from the
      gelatin affinity column, we expected that these form the complexes. These results
      indicate that the complexes of proMMP-2/TIMP-2 and MMP-2/TIMP-2 exist in HFF.
      (Reprod Med Biol 2003; 2: 115-119).

PMID- 29662378
TI  - Validity of trans-rectal ultrasound-guided embryo transfer against retroflexed
      uterus.
AB  - Background:  Embryo transfer is one of the most critical steps affecting the
      success of in vitro fertilization/intracytoplasmic sperm injection-embryo
      transfer. It has been reported that uterine contraction caused by touching the
      uterine fundus at the time of embryo transfer decreased the pregnancy rate. It
      was demonstrated that there is a significant rise in the pregnancy rate by
      adequate positioning of embryos. Transabdominal ultrasound-guided embryo transfer
      has been reported to improve the pregnancy rate compared with the clinical touch
      method. The improvement of the pregnancy rate under ultrasound guidance can be
      attributed to the accurate positioning of the embryos aided by good visualization
      without touching the uterine fundus. However, sometimes difficulties are
      encountered when visualizing the tip of the catheter in cases where the patient
      has a retroflexed uterus. Methods:  In the present study, we investigated the
      difference in the pregnancy rates and in the implantation rates between
      transabdominal ultrasound-guided group and trans-rectal ultrasound-guided group
      in retroflexed cases. Results and Conclusion:  We found that the pregnancy rate
      and the implantation rate were higher among the trans-rectal group compared with
      the transabdominal group in retroflexed cases. The difference between the two
      groups was statistically significant. (Reprod Med Biol 2003; 2: 159-163).

PMID- 29662379
TI  - Clinical evaluation of frozen/thawed embryo transfer following transport of
      oocytes and embryos.
AB  - Background and Aims:  We evaluated the efficacy of the transport oocyte/embryo
      frozen/thawed embryo transfer method, in which oocytes or embryos were
      transported from satellite clinics to the main assisted reproductive technology
      (ART) center, and surplus embryos were placed in cryopreservation. Methods:  We
      evaluated 41 cycles in 34 patients in the transport oocyte group (TO group). In
      the TO group the oocytes were collected at the satellite clinics, transported to
      the main ART center and underwent in vitro fertilization or intracytoplasmic
      sperm injection. Surplus embryos were used for frozen/thawed embryo transfer. We
      also evaluated 17 cycles in 10 patients in the transport embryo group (TE group),
      where surplus embryos were transported to the main ART center and used for
      frozen/thawed embryo transfer; and 189 cycles in 134 patients in the center group
      (C group), where surplus embryos collected at the same time at the main ART
      center were used for frozen/thawed embryo transfer. Oocytes were transported from
      satellite clinics in HEPES buffered human tubal fluid (HTF) culture medium, and
      embryos in 30% synthetic serum substitute + HEPES buffered HTF, using a portable
      incubator we devised. Results:  The proportions of undamaged embryos after
      freeze/thawing were 47% for the C group, 46% for the TO group, and 46% for the TE
      group. The numbers of embryos transferred were 2.0 +/- 0.7 for the C group, 2.0
      +/- 0.6 for the TO group, and 2.2 +/- 0.4 for the TE group. The rate of embryo
      transfer was 63% for the C group, 68% for the TO group, and 76% for the TE group.
      Pregnancy rates per patient were 16% for the C group, 24% for the TO group, and
      40% for the TE group. The embryo survival rates (number of embryos with >=50%
      viable blastomeres/total number of embryos) were 55% for the C group, 60% for the
      TO group, and 54% for the TE group. No significant differences were seen between
      the C group and either the TO or TE groups in any of these parameters.
      Conclusions:  Favorable results were achieved with the transport oocyte/embryo
      frozen/thawed embryo transfer method, and it is suitable for widespread clinical
      application. (Reprod Med Biol 2004; 3: 1-8).

PMID- 29662380
TI  - Analysis of limited fertility in intracytoplasmic sperm injection of sperm
      obtained by electroejaculation.
AB  - Background and Aims:  We correlated findings in semen from patients with
      ejaculatory dysfunction with results of in vitro fertilization using their
      electroejaculated sperm. Methods and Results:  Electroejaculation was carried out
      in six patients with the above-mentioned criteria for a total of eight times.
      Sperm was obtained in six attempts. Intracytoplasmic injection of these sperm was
      performed in 156 eggs. Sixty-seven eggs were fertilized; most of these were
      injected with motile sperm. Two women became pregnant, both after injection with
      motile sperm. As previously reported, electroejaculated sperm showed low motility
      and a low fertilization rate, but even motile sperm had a low fertilization rate.
      Conclusion:  The results of the present study suggest the importance in
      fertilization of undetermined factors in addition to sperm motility. (Reprod Med
      Biol 2004; 3: 9-12).

PMID- 29662381
TI  - Selected single blastocyst transfers maintained pregnancy outcome and eliminated
      multiple pregnancies.
AB  - Background:  Transfer of more than one embryo following in vitro
      fertilization/intracytoplasmic sperm injection cycles have increased pregnancy
      rate at the cost of increasing the incidence of triplets and twins. It has been
      proposed that prolonged culture to the blastocyst stage would automatically
      result in the selection of good quality embryos for transfer and minimize the
      incidence of triplets and twins. Methods and Results:  The objectives of the
      present retrospective analysis were to examine the pregnancy outcome, multiple
      pregnancy and related data following: (i) single blastocyst transfer (BT) and
      double BT; (ii) single BT in patients belonging to different age groups; and
      (iii) good, fair or poor quality of BT. A total of 260 BT were carried out
      between August 1998 and July 2002 and they are included in the current study.
      Sixty of the 260 BT patients received a single BT, and 41 of them received
      selected single good quality BT (SSBT). The implantation rate has no significant
      difference between following single BT (53.3%) and double BT (42.8%). No multiple
      pregnancy occurred following single BT, while significantly higher (P < 0.05)
      multiple pregnancy rate was observed following a double BT (45.8%). The clinical
      pregnancy and implantation rates following a single BT were similar (P > 0.05) in
      patients belonging to <30 years (62.5%), 30-34 years (57.9%) and 35-39 years old
      (35.8%). Conclusion:  Selected single good quality BT maintained pregnancy and
      avoided multiple pregnancies. It is recommended for patients with a risk for high
      order multiple pregnancy. (Reprod Med Biol 2004; 3: 13-18).

PMID- 29662382
TI  - Life-table analysis of artificial insemination pregnancy rates for couples with
      male factor and idiopathic infertility.
AB  - Background:  In the summer of 2002, standard guidelines for the application of
      assisted reproductive technology were reported by a research group of the
      Ministry of Health, Labor and Welfare. The present study aimed to examine the
      relationship between the number of cycles of artificial insemination and the
      cumulative pregnancy rates according to the cause of infertility. Methods: 
      Patients who experienced their first cycle of artificial insemination during the
      period of January 1999-December 2002 were included in the study and were divided
      into a male factor infertility group and an idiopathic infertility group.
      Cumulative pregnancy rates resulting from artificial insemination with the
      husband's semen were calculated by the life-table approach. Results:  During the
      study period, 139 couples entered the assisted reproduction program and underwent
      581 cycles. Significant differences were observed in cumulative pregnancy rates
      between the two groups. Conclusion:  It is recommended that couples with male
      factor infertility and who fail to conceive within six or seven cycles of
      intrauterine insemination, consider a modification of treatment strategy such as
      in vitro fertilization, because cumulative pregnancy rates of this group were
      reached at a plateau within six or seven cycles. In contrast, patients with
      idiopathic infertility, the cumulative pregnancy rates appeared to increase
      constantly with each subsequent cycle. It is important to consider modifications
      of treatment strategy in the light of the cause of infertility. (Reprod Med Biol
      2004; 3: 27-31).

PMID- 29662384
TI  - Bisphenol A-induced morphological alterations in Sertoli and spermatogenic cells
      of immature Shiba goats in vitro: An ultrastructural study.
AB  - Background and aims: There is no information currently available regarding the
      effects of bisphenol A (BPA) on testes in ruminants. Therefore, to establish and
      clarify the effects of BPA in ruminants, testicular tissue cultures were obtained
      from immature Shiba goats. Methods: The testes of 2-month-old Shiba goats were
      cut into smaller pieces and seeded in medium. At 1, 3, 6 and 9 h after
      administration of various concentrations of BPA, the specimens underwent light
      and transmission electron microscopic observations Results: At 1 h after BPA
      treatment, vacuolization and nuclear membrane rupture appeared within the
      nucleoplasm and cytoplasm of Sertoli cells. Such alterations tended to gradually
      increase in number in time- and dose-dependent manners. Thus, because of BPA
      treatment, apoptotic spermatogenic cells, necrotic spermatogenic cells, apoptotic
      Sertoli cells and necrotic Sertoli cells could be identified. Particularly in the
      Sertoli cell, ruptured vesicles could be found within the multivesicular nuclear
      body. Conclusion: The treatment with BPA at a low concentration tends to lead
      spermatogenic and Sertoli cells to apoptosis, whereas a higher concentration
      tends to lead spermatogenic and Sertoli cells to necrosis. Therefore, this study
      showed that testicular tissue culture is an advantageous avenue for screening the
      testicular toxicity of chemicals in ruminants. (Reprod Med Biol 2004; 3: 205
      210).

PMID- 29662383
TI  - Functional roles of cell surface peptidases in reproductive organs.
AB  - A number of biologically active peptides have been proposed to regulate function
      and differentiation of reproductive organs in an autocrine and/or paracrine
      fashion. Regulation of the local concentrations of these peptides is one of the
      important factors influencing their physiological effects on target cells.
      Membrane-bound cell surface peptidases can activate or inactivate biologically
      active peptides before peptide factors access their receptors on the cell
      surface. Aminopeptidase A (EC 3.4.11.7), placental leucine aminopeptidase (EC
      3.4.11.3), aminopeptidase-N/CD13 (EC 3.4.11.2), dipeptidyl peptidases IV/CD26
      (EC.3.4.14.5), carboxypeptidase-M (EC 3.4.17.12), neutral endopeptidase/CD10 (EC
      3.4.24.11) and endothelin converting enzyme-1 (EC 3.4.23) are differentially
      expressed on the ovary, endometrium and placenta. The inhibition of enzyme
      activity affects steroid hormone production by granulosa and thecal cells,
      decidualization of endometrium and migration of extravillous trophoblasts. These
      findings suggest that membrane-bound cell surface peptidases are local regulators
      for cellular growth and differentiation in reproductive organs by controlling
      extracellular concentration of peptide factors. (Reprod Med Biol 2004; 3: 165 
      176).

PMID- 29662385
TI  - Serine/threonine phosphorylation associated with hamster sperm hyperactivation.
AB  - Background and Aims: Mammalian sperm activation and hyperactivation is regulated
      by protein phosphorylation. Although tyrosine phosphorylation is considered very
      important, several studies have investigated whether serine and threonine
      phosphorylation are also associated with sperm activation and hyperactivation,
      and that was also the aim of the present study. Methods: Protein phosphorylation
      of hamster spermatozoa was detected by Western blotting using antiphospho-amino
      acid monoclonal antibodies after tricine sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis. Amino acid sequences were analyzed using a peptide
      sequencer. Results: Four proteins were phosphorylated at serine residues during
      hyperactivation via activation and their approximate molecular weights were 90,
      38, 32 and 10 kDa, respectively. Five proteins were phosphorylated or
      dephosphorylated at threonine residues and their approximate molecular weights
      were 90, 70, 65, 35 and 10 kDa, respectively. The 10-kDa protein corresponded to
      a previously reported 10-kDa tyrosine phosphoprotein. N-terminal sequences of the
      10-kDa protein were similar to carcinustatin, which is a neuropeptide.
      Conclusions: During hyperactivation, four serine phosphorylation and five
      threonine phospho- or dephosphorylations occurred, which suggested that the 10
      kDa protein was phosphorylated at tyrosine residues when spermatozoa were
      activated and then dual-phosphorylated at the serine and threonine residues
      during hyperactivation. (Reprod Med Biol 2004; 3: 223-230).

PMID- 29662386
TI  - Fertilization and preimplantation development of mouse oocytes after prolonged
      incubation with caffeine.
AB  - Background and Aims:  Previous studies have shown that caffeine might cause
      artificial dephosphorylation at threonine-14 and tyrosine-15 of the p34cdc2
      catalytic subunit of maturation-promoting factor (MPF), elevate MPF activity in
      metaphase II oocytes cultured for a prolonged period, and that caffeine decreases
      fragmentation in oocytes cultured for up to 96 h. Methods:  Studies were carried
      out on: (i) the effect of caffeine on the morphological status of oocytes
      cultured for 96 h; (ii) the parthenogenetic activation and the fertilization of
      oocytes incubated in a medium that contained caffeine, and (iii) the
      fertilization and preimplantation development ability of zona-intact and zona
      free oocytes by in vitro fertilization (IVF) and by intracytoplasmic sperm
      injection. Results:  In parthenogenetic activation, the incidence of diploid
      parthenotes in 24-h caffeine-treated oocytes was significantly higher than 24-h
      non-treated oocytes. For fertilizability of these oocytes, a significant increase
      in the fertilization rate resulted from IVF after 12-h caffeine incubation.
      Although no fertilized eggs were observed after intracytoplasmic sperm injection
      in 24-h non-treated oocytes, fertilized eggs were observed in caffeine-treated
      oocytes. MPF activation occurs in relation to nuclear/spindle position, and
      mitotic spindles and actin filaments determine the site of cleavage during
      cytokinesis. Spindle disruption does not cause cytofragmentation, but does induce
      cell cycle arrest. Conclusion:  Based on our results, although caffeine might
      increase MPF activity, prolonged time in any incubation causes some disruption of
      cytoskeletal filaments, which might be responsible for the poor development of
      caffeine-treated oocytes. (Reprod Med Biol 2004; 3: 245-251).

PMID- 29662387
TI  - Role of tumor necrosis factor-alpha in Gram-negative bacterial
      lipopolysaccharides induced implantation failure.
AB  - Background and aims:  Gram-negative bacterial lipopolysaccharides (LPS) are known
      causative agents for pregnancy loss in mothers with genital tract infections. In
      this study, we attempt to test the role of tumor necrosis factor-alpha (TNF
      alpha) in the normal physiological processes of preimplantation embryonic
      development and LPS induced pregnancy loss in mice. Since the preimplantation
      mouse embryos grow in an unattached state for a considerable period (day 1-4.5)
      of its development in the maternal environment, it is possible that a critical
      level of soluble and biologically active TNF-alpha is maintained in the maternal
      environment, and that any alteration in this could lead to implantation failure.
      Here we determine the pattern and level of expression of TNF-alpha gene in
      preimplantation stage embryos and uterus collected from control and LPS treated
      pregnant animals during different stages of preimplantation period of pregnancy
      by reverse transcriptase-polymerase chain reaction. Methods:  The concentrations
      and biological activity of soluble TNF-alpha protein present in oviductal fluid
      (OF) and uterine fluid (UF), in the normal and LPS treated animals, were
      determined by enzyme-linked immunosorbent assay and 3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium bromide assay on L929 cells, respectively. TNF-alpha was
      also given i.p. to study its effect on implantation. Results:  An early
      expression of TNF-alpha messenger ribonucleic acid in the preimplantation stage
      embryos collected from LPS treated animals was observed along with a significant
      rise in the level of biologically active soluble TNF-alpha in the OF. Similarly,
      the level of bioactive and soluble TNF-alpha present in the UF from LPS treated
      animals was significantly higher as compared to the control on day 4.42 of
      pregnancy. Conclusions:  TNF-alpha given i.p. exerted similar effects on
      pregnancy as that of LPS. An incessant exposure of the preimplantation stage
      embryos to significantly high levels of maternal bioactive free/soluble TNF
      alpha, and an alteration in the normal pattern of its expression in the
      preimplantation stage embryos may be one of the causes of failure of implantation
      leading to poor pregnancy outcome in LPS treated mouse. (Reprod Med Biol 2005; 4:
      79- 89).

PMID- 29662388
TI  - Histone acetylation in reproductive organs: Significance of histone deacetylase
      inhibitors in gene transcription.
AB  - Acetylation of histones is cooperatively regulated by two groups of enzymes,
      histone acetyltransferases and histone deacetylases. Histone acetylation status
      plays a fundamental role in the level of gene transcription; numerous studies
      have demonstrated that histone deacetylase inhibitors cause cell growth arrest,
      apoptosis, and differentiation in various cells including human mammary gland and
      endometrial cells by altering transcription of a small number of genes. A recent
      study has also shown that a highly acetylated histone status alters cell
      motility. After the present review of the published reports on the mechanisms
      underlying histone acetylation and in vitro effects of histone deacetylase
      inhibitors, we conclude that this class of agents may have potential not only as
      anticancer drugs, but also as inducers of differentiation and/or motility for
      benign gynecologic conditions such as endometriosis and disorders of endometrial
      differentiation and dysfunction. (Reprod Med Biol 2005; 4: 115-122).

PMID- 29662389
TI  - Y chromosome and new concept of azoospermia factor.
AB  - The completion of a draft sequence of the entire human genome in 2001 was
      followed by a complete sequencing of the Y chromosome in 2003. It is now possible
      to refer to a physical map of the Y chromosome. The Y chromosome can be
      classified into X-transposed, X-degenerate and ampliconic sequences depending on
      the origins of its sequences. In particular, the ampliconic sequences are
      complexes of massive palindrome structures in which sequences having higher than
      99.9% homology are present symmetrically. Interestingly, palindromic repeats may
      undergo frequent gene conversion associated with intrachromosomal recombination
      and play an important role in the maintenance of the genetic materials of the Y
      chromosome. The azoospermia factor (AZF) region of the ampliconic region is the
      most probable candidate for spermatogenesis, and forms a palindrome structure.
      Thus, there is a limit in the detection of microdeletion using conventional
      sequence-tagged sites based on polymerase chain reaction because of their
      structure. It is now necessary to update the AZF concept. (Reprod Med Biol 2005;
      4: 123-128).

PMID- 29662390
TI  - Estrogen-related receptor in reproductive organs.
AB  - Estrogen-related receptor (ERR) was studied in the placenta and uterine
      endometrium, especially endometrial cancers, among reproductive organs. In the
      placenta, the estrogen receptor (ER) alpha and beta mRNA levels increased from
      the first to the second trimester, and then decreased until normal term delivery.
      Estrogen-related receptor alpha, beta and gamma mRNA levels gradually increased
      up to the second trimester, and then comparatively rapidly increased until normal
      term delivery. In endometrial cancers, ER alpha and beta mRNA levels decreased
      with clinical stage, myometrial invasion and dedifferentiation. Estrogen-related
      receptor alpha levels increased with clinical stage and myometrial invasion, and
      the ERR gamma levels increased with myometrial invasion.  Estrogen-related
      receptors can bind to the steroid receptor coactivator family without any
      ligands, and drive transcription activity of the target genes. The manner of ERR
      and ER gene expressions might show a competitive interaction associated with the
      use of common cofactors. It is speculated that the upregulation of ERR is related
      to the placental growth after the downregulation of ER from the second trimester
      until delivery, and that ERR alpha and gamma are candidates for prognostic
      factors in endometrial cancer, although ERR are not directly related to tumor
      growth and advancement of endometrial cancer. (Reprod Med Biol 2005; 4: 129-131).

PMID- 29662391
TI  - Changes in the heart rate and plasma epinephrine and norepinephrine
      concentrations of the stallion during copulation.
AB  - Aim:  The physiological indexes of the copulatory behavior of the stallion have
      not been investigated in detail and may differ from those of other species, such
      as humans and rats. Methods:  In order to understand the breeding capability of
      various stallions, their behavior during copulation was observed, and heart rate
      (HR) and the plasma concentrations of norepinephrine (NA) and epinephrine (Ad)
      were measured sequentially for a total of 13 copulations carried out during 2
      days. Results:  The mean HR at rest was 35.3 +/- 0.9 beats per minute (b.p.m.)
      and it peaked during mounting (162.1 +/- 5.4 b.p.m.). The HR at ejaculation was
      145.7 +/- 5.1 b.p.m, which was less than the peak. The plasma concentrations of
      NA and Ad showed similar changes to the HR; immediately after ejaculation they
      were, respectively, 4.7-fold and 1.9-fold higher than the resting values and
      there was a difference in the degree of increase of each catecholamine.
      Conclusions:  The present results show that in the stallion the HR peaks at
      mounting and there is a greater change in the activity of the sympathetic nervous
      system because of the short-term, highly intense exercise performed during
      copulation. It is considered that this, combined with the particular mental
      stress placed on the stallion during copulation, has the potential to cause
      sudden cardiac death. (Reprod Med Biol 2005; 4: 143-148).

PMID- 29662392
TI  - Food intake and leptin concentrations of lactating rats nursing various sized
      litters.
AB  - Purpose:   Leptin, the obesity (ob) gene product, has been proposed as an adipose
      related satiety factor. It might act as a signal, from peripheral adipose stores
      to the central nervous system, to decrease food intake and increase energy
      expenditure. Conversely, low leptin concentrations after fasting or energy
      restriction might act to increase food intake. The present study investigated the
      role of the suckling stimulus in the mechanisms regulating body weight, food
      consumption and leptin concentration in lactating rats nursing different sized
      litters. Methods:   The day of parturition was designated as day 0 of lactation.
      The rats were allocated randomly to three groups and the number of pups per
      litter was adjusted within one day of birth to eight (Group A), four (Group B)
      and two (Group C), with equal numbers of both sexes. From day 1 to day 10 of
      lactation, the separate weights of the mothers and pups, and the mothers' food
      intake were measured daily. On day 10, the rats were decapitated and blood was
      collected from the mothers for measurement of serum concentrations of leptin by
      ELISA. Results:   Food intake by the mothers in Groups B and C decreased by about
      20% and 30%, respectively, by day 10 of lactation, compared with Group A, but the
      serum leptin concentrations of those in Group C increased by about 80%, compared
      with Groups A and B. There was a high positive correlation between leptin
      concentration and fat pad weight. Conclusion:   The findings suggest that the
      smaller litter in Group C reduced the energy cost of lactation, which induced an
      increase in the serum leptin concentration. (Reprod Med Biol 2005; 4: 203-206).

PMID- 29662393
TI  - Heterotopic cervical pregnancy with preservation of the intrauterine gestation.
AB  - We present a case of heterotopic cervical pregnancy where intrauterine gestation
      was preserved successfully. A 40-year-old Japanese woman presented with
      heterotopic cervical pregnancy after intracytoplasmic sperm injection with
      elongated spermatid. An ultrasound examination showed heterotopic cervical
      pregnancy. Intrauterine gestation was preserved successfully with the use of
      local vasopressin injection, followed by curettage of cervical implantation and
      local methotrexate injection. The cervical pregnancy resolved, and a healthy full
      term infant was delivered. When early diagnosis of a heterotropic cervical
      pregnancy is made, selective reduction of a cervical implantation might allow
      preservation of the intrauterine gestation, without hysterectomy. (Reprod Med
      Biol 2005; 4: 221-223).

PMID- 29662394
TI  - Predicting sperm retrieval rates in testicular sperm extraction for azoospermia
      according to endocrine profiles.
AB  - Background and Aims:  The present study was carried out to examine the predictive
      value of endocrine profiles as indicators of the sperm retrieval rate on
      testicular sperm extraction (TESE) in azoospermic men. Methods:  Prior to TESE,
      the serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH),
      prolactin, testosterone, dihydrotestosterone (DHT), estradiol and 17 alpha
      hydroxyprogesterone were measured and the sagittal cross-sections of the testis
      were acquired using ultrasonography. Results:  The sperm retrieval rates
      according to the cause of azoospermia were 40% for idiopathic azoospermia, and
      100% for obstructive azoospermia, cryptorchidsm and ejaculatory disorder. Based
      on the endocrinological profiles, the sperm retrieval rates showed significant
      differences at 100% for FSH  15 mIU/mL or LH  2 mIU/mL, 0% for FSH > 60 mIU/mL or
      LH > 12 mIU/mL, and 33% for the intermediate groups (P < 0.01). Comparison of the
      retrieval of spermatozoa and serum DHT level for the intermediate group also
      showed a significant difference, with retrieval rates of 58% for DHT  0.5 ng/mL
      and 0% for DHT > 0.5 ng/mL (P < 0.01). Conclusions:  The etiology, serum FSH, LH
      and DHT levels are useful in predicting the sperm retrieval rates on TESE in
      azoospermic patients. (Reprod Med Biol 2005; 4: 239-245).

PMID- 29662395
TI  - Effects of in vivo exposure to eggs with sperm-immobilizing antibodies in
      follicular fluid on subsequent fertilization and embryo development in vitro.
AB  - Aims:  It has been shown that supplementation of patients' sera that contains
      sperm-immobilizing antibodies results in failure of fertilization and embryo
      development in vitro. The present study was carried out to investigate if
      exposing retrieved eggs to a high number of sperm-immobilizing antibodies in the
      follicular fluid (FF) in vivo affected subsequent fertilization and embryo
      development in vitro, even if they were washed with an antibody-free culture
      medium. Methods:  Patients' sera and their FF were collected in 15 in vitro
      fertilization-embryo transfer (IVF-ET) or intracytoplasmic sperm injection-embryo
      transfer (ICSI-ET) treatment cycles from 11 infertile women with sperm
      immobilizing antibodies in their sera. Quantitative sperm-immobilizing antibody
      titers (SI50 titers) in the sera and FF were evaluated. The fertilization rate,
      good-quality embryo rate and implantation rate by IVF-ET were compared between
      infertile patients having higher (10<=) SI50 titers and lower (<10) SI50 titers
      in their FF. Results:  There was a significant correlation in the SI50 titers
      between the patients' sera and their FF (P < 0.0001). After thoroughly washing
      the collected eggs in culture medium without the patient's serum before IVF,
      there was no difference in the fertilization rate in the patients with high
      (10<=) and low (<10) SI50 titers in their FF (P = 0.62). However, the good
      quality embryo rate in the patients with a high SI50 titer was significantly
      lower than patients with a low antibody titer (P < 0.05). There was no
      significant difference in the implantation rate between the two groups (P =
      0.33). Conclusions:  Similar amounts of sperm-immobilizing antibodies existed in
      the patients' FF and in their sera. ICSI did not seem to be necessary in patients
      having the antibodies if their sera were not supplemented in the culture media.
      Even with careful manipulation of eggs, it might be suggested that the harmful
      effects of sperm-immobilizing antibodies on embryo development cannot be
      completely avoided, especially in patients with high SI50 titers in the FF.
      (Reprod Med Biol 2006; 5: 137-143).

PMID- 29662396
TI  - Proliferation of spermatogonial stem cells and spermatogenesis in vitro.
AB  - Detection of spermatogonial stem cells (SSC) became possible 10 years ago, with
      the transplantation of germ cells into the seminiferous tubules of mice. Using
      this assay system, attempts to maintain and expand SSC in vitro finally bore
      fruit. Gonocytes from neonatal mice and spermatogonial stem cells from adult mice
      were plated on feeder cells in a medium supplemented with Glial cell line-derived
      neurotrophic factor (GDNF) along with certain other factors. The germ cells that
      emerged under such conditions, named germline stem (GS) cells, proliferated
      exponentially through self-renewing division. GS cells in vitro show features of
      differentiation as well. Some expressed c-kit, which is a cell surface marker of
      differentiating spermatogonia. Therefore, it seems that GS cells undergo both
      self-renewing and differentiating cell divisions in vitro. There is a century of
      history behind attempts to reproduce spermatogenesis in vitro and significant
      progress has been made. Nonetheless, there are few established culture-based
      protocols for recreating spermatogenesis in vitro. GS cells would be an ideal
      starting material in this regard. (Reprod Med Biol 2006; 5: 169-174).

PMID- 29662397
TI  - Role of oocyte-specific genes in the development of mammalian embryos.
AB  - Studies on oocyte-specific genes are important in understanding the genetic
      pathways essential for folliculogenesis, oogenesis and early embryogenesis.
      Although the molecular mechanisms regulating oocyte growth and embryo development
      in mammals have partially been unraveled by gene knockout studies, many aspects
      concerning reproduction remain to be determined. Development of mammalian embryos
      starts with the fusion of sperm and egg. After fertilization, the first major
      developmental transition, maternal to zygotic transition, occurs at the specific
      stages of preimplantation development in each mammal. The transition is called
      zygotic gene activation (ZGA) or embryonic genome activation. The ZGA is one of
      the most important events that occur during preimplantation development; however,
      the mechanism of the event remains unknown. Because the development until the
      transition is maintained by maternally inherited proteins and transcripts stored
      in the oocytes, it is highly likely that these products play an important role in
      the initiation of ZGA. Several maternal-effects genes that are specifically
      expressed in oocytes have been identified and their involvement in
      preimplantation development has been revealed. Therefore, to study oocyte
      specific gene regulation would help not only to understand the precise mechanisms
      of mammalian development, but also to show the mechanisms of reproductive
      disorders, such as premature ovarian failure and infertility. (Reprod Med Biol
      2006; 5: 175-182).

PMID- 29662399
TI  - Prediction of candidates for seminal tract reconstructive surgery among patients
      with clinically suspected idiopathic or inflammatory obstructive azoospermia.
AB  - Background and Aim:  We reviewed the findings of scrotal exploration,
      histological examination and clinical parameters in patients with clinically
      suspected idiopathic or inflammatory obstructive azoospermia without confirmation
      by isolated testis biopsy in advance. Methods:  The present study included 27
      patients who underwent scrotal exploration for the purpose of vasoepididymostomy,
      with simultaneous testicular sperm extraction. Results:  Sperm in the epididymis
      was proven in 11 patients (40.7%). In two of these patients, the vas deferens was
      obstructed on the seminal vesicle side. Histologically, normal spermatogenesis
      was seen in all patients. The 16 (59.2%) patients with no sperm in the epididymis
      included two with normal spermatogenesis. Serum follicle stimulating hormone
      (FSH) levels were significantly higher in men with no sperm in the epididymis in
      contrast to those in men with sperm proven in the epididymis (P = 0.0057). By
      using a cut-off point of 6.02 mIU/mL, serum FSH can predict the existence of
      sperm in the epididymis, with a sensitivity of 81.8%, a specificity of 81.2% and
      a positive predictive value of 75.0%. Conclusion:  No more than a third of the
      patients in the present study who had clinically suspected obstructive
      azoospermia were actual candidates for vasoepidydimostomy. A serum FSH level cut
      off point of 6.02 mIU/mL might be useful to determine its indication. (Reprod Med
      Biol 2006; 5: 211-214).

PMID- 29662398
TI  - Comparative study of Sperm Motility Analysis System and conventional microscopic
      semen analysis.
AB  - Background and Aim:  Conventional manual sperm analysis still shows variations in
      structure, process and outcome although World Health Organization (WHO)
      guidelines present an appropriate method for sperm analysis. In the present study
      a new system for sperm analysis, Sperm Motility Analysis System (SMAS), was
      compared with manual semen analysis based on WHO guidelines. Materials and
      methods:  Samples from 30 infertility patients and 21 healthy volunteers were
      subjected to manual microscopic analysis and SMAS analysis, simultaneously. We
      compared these two methods with respect to sperm concentration and percent
      motility. Results:  Sperm concentrations obtained by SMAS (Csmas) and manual
      microscopic analyses on WHO guidelines (Cwho) were strongly correlated (Cwho =
      1.325 * Csmas; r = 0.95, P < 0.001). If we excluded subjects with Csmas values
      >30 * 106 sperm/mL, the results were more similar (Cwho = 1.022 * Csmas; r =
      0.81, P < 0.001). Percent motility obtained by SMAS (Msmas) and manual analysis
      on WHO guidelines (Mwho) were strongly correlated (Mwho = 1.214 * Msmas; r =
      0.89, P < 0.001). Conclusions:  The data indicate that the results of SMAS and
      those of manual microscopic sperm analyses based on WHO guidelines are strongly
      correlated. SMAS is therefore a promising system for sperm analysis. (Reprod Med
      Biol 2006; 5: 195-200).

PMID- 29662400
TI  - Influence of the hypogonadism (hgn) locus on female reproduction and ovarian
      development in an altered genetic background.
AB  - Background and Aims:  The hypogonadic rat (hgn/hgn) shows male sterility
      controlled by a single recessive gene hgn. The hgn/hgn females detected by the
      presence of renal hypoplasia in the HGN inbred strain show a reduced fertility.
      Recently, the gene responsible for male hypogonadism was mapped on chromosome 10
      by a linkage analysis using only male backcross progeny. Because backcross
      females could not be categorized as affected or normal because of variations in
      their renal sizes, we could not examine female fertility in the backcross
      progeny. In the present experiment, we examined whether the gene mapped on rat
      chromosome 10 has any influences on female reproduction and ovarian development.
      Methods:  The assumptive hgn/hgn females were identified in the backcross progeny
      by microsatellite markers closely linked to the hgn locus. Postnatal body growth,
      the weights of reproductive organs, estrus cycle and ovarian histology were
      examined. In addition, backcross embryos were genotyped, and their body growth
      and ovarian development was examined. Results:  The hgn/hgn females showed growth
      retardation, a short reproductive life and an abnormal ovarian histology as
      adults. Regarding embryonic development, hgn/hgn females showed body growth
      retardation and ovarian hypoplasia. Conclusion:  The mutation of the hgn mapped
      on chromosome 10 causes not only male sterility but also female reduced fertility
      related to ovarian hypoplasia beyond the altered genetic background. (Reprod Med
      Biol 2006; 5: 227-234).

PMID- 29662401
TI  - Effect of fructose on motility, acrosome reaction and in vitro fertilization
      capability of boar spermatozoa.
AB  - Aim:  The present study was carried out to investigate the effects of fructose
      supplementation in glucose containing mTALP medium on motility, acrosome reaction
      and in vitro fertilization capability of boar spermatozoa. Methods:  Boar
      spermatozoa were preincubated, swum-up, resuspended and then incubated for 6 h in
      mTALP medium supplemented with 0, 0.5, or 1.0 mmol fructose in the presence of
      5.0 mmol glucose. After completion of the specified incubation period, motility
      was determined subjectively on the basis of speed of progression and on the type
      of forward movement of spermatozoa; acrosome status was evaluated by applying a
      triple staining technique; and in vitro fertilization capability was assessed by
      acetic-orcein staining. Results:  The combination of fructose and glucose (0.5 +
      5.0 mmol) supplements in mTALP medium improved sperm motility significantly (P <
      0.05), more than glucose alone (5.0 mmol) at 2-6 h of incubation. Acrosome
      reaction (live spermatozoa) and the sperm penetration rate was increased
      significantly (P < 0.05) when the spermatozoa were treated with the combination
      of fructose and glucose compared with glucose alone, but the incidence of
      polyspermy was not significantly different between the treatments. Conclusion: 
      These results suggest that the combination of glucose and fructose as supplements
      in mTALP medium improve the progressive motility, acrosome reaction and
      fertilization capability of boar spermatozoa. (Reprod Med Biol 2006; 5: 255-261).

PMID- 29662402
TI  - Serum steroids concentration might be used for monitoring the growth of follicles
      in friendly in vitro fertilization.
AB  - Background:  Steroid levels have been used as the predictive parameters for
      oocyte maturation and embryo development. In the present study, estradiol and
      progesterone concentrations in the follicular fluid and serum were evaluated in
      conventional in vitro fertilization (IVF; follicle stimulating hormone [FSH]
      and/or human menopausal gonadotropin [hMG] after pituitary desensitization) and
      friendly IVF (no stimulation, clomiphene citrate, small dose of FSH or hMG
      without pituitary desensitization). The purpose of the present study was to
      evaluate the differences in steroid distribution between conventional and
      friendly IVF. Methods:  Concentrations of estradiol, progesterone, FSH, and
      luteinizing hormone (LH) in serum and follicular fluid were determined in
      conventional and friendly IVF protocols by an enzyme-linked immunosorbent assay
      kit. Correlations between follicular fluid and serum steroid concentrations in
      these different protocols, and between pregnant cycles and steroid concentrations
      were evaluated. Results:  Two hundred and thirty-four samples of follicular fluid
      from 74 IVF patients were analyzed. In conventional IVF, there was no
      relationship in steroid levels in between follicular fluid and serum steroids,
      whereas serum steroid concentrations correlated with the number of developing
      follicles. There was a relationship between the serum and follicular fluid
      estradiol levels (r = 0.467, P < 0.0001) as well as progesterone levels (r =
      0.227, P = 0.0488) from friendly IVF patients. Conclusions:  Serum steroid
      concentrations were mainly associated with the number of developing follicles. In
      the cases of friendly IVF, which had a small number of developing follicles,
      serum steroids might be used to monitor follicular fluid steroid concentrations.
      (Reprod Med Biol 2006; 5: 277-282).

PMID- 29662404
TI  - Epigenetics in assisted reproductive technology.
AB  - It has been reported that the rates of epigenetic disorders such as Angelman
      syndrome (AS) and Beckwith-Wiedemann syndrome (BWS) are high in offspring
      conceived by assisted reproductive technology (ART). Angelman Syndrome is
      characterized by intellectual disability and BWS is known as large offspring
      syndrome (LOS). Weight abnormalities have also been reported in cloned animals.
      Possible factors underlying these findings include inherent gamete
      characteristics, influence of in vitro culture and peculiarity of ART methods. It
      is important to conclusively determine whether such epigenetic abnormalities are
      present in children conceived by ART, so as to consider the health of next
      generations.

PMID- 29662405
TI  - Useful marker for the estimation of a recombination pair in the partial
      azoospermia factor c (gr/gr) deletion using quantitative real-time polymerase
      chain reaction.
AB  - Background and aims:  Azoospermia factor c (AZFc) microdeletions are associated
      with male infertility and are caused by intrachromosal recombination between
      homologous repetitive sequence segments. Partial AZFc deletion (gr/gr) has been
      reported in male factor infertility. In the present study, we established
      detecting the copy number using quantitative real-time polymerase chain reaction
      (qRT-PCR) with the genome DNA, and assessed the association of the recombination
      pair set of gr/gr deletion and deleted in azoospermia copies. Furthermore, we
      determined the clinical significance of differential recombination patterns of
      gr/gr deletion, and compared them with azoospermia and proven fertile volunteers,
      with both groups having gr/gr deleted Japanese subjects. Materials and methods: 
      A total of 16 Japanese subjects with idiopathic azoospermia, and 13 proven
      fertile men with gr/gr deletion, were studied. qRT-PCR was used for the
      estimation of an identical site number. Results:  The g1/g2 deletion was found in
      69.2% (9/13) in proven fertile men and in 75% (12/16) of idiopathic infertile
      men. The gr/gr deletion could result in the recombination of g1/g2 segments.
      Furthermore, there was no difference in the position of deletion between
      azoospermic patients and controls (P = 0.59). Conclusion:  There was no
      association between the loss of DAZ cluster and azoospermia in gr/gr deletion.
      This suggests that most of the partial deletions are neutral variants.

PMID- 29662406
TI  - Effect of fatty acids bound to bovine serum albumin-V on acrosome reaction and
      utilization of glucose in boar spermatozoa.
AB  - Aim:  The present study has been designed with the objective of determining if
      fatty acids bound to bovine serum albumin-V (BSA-V) can improve motility,
      viability, and increase acrosome reaction (AR) and utilization of glucose in boar
      spermatozoa. Methods:  Boar spermatozoa were washed, swum-up and incubated at 37
      degrees C for 6 h in TALP medium supplemented with fatty acids bound to bovine
      serum albumin fraction V (BSA-V), fatty acid free BSA (BSA-FAF), polyvinyl
      alcohol + main fatty acids bound to BSA-V (PVA + FA) and PVA. Sperm motility,
      viability, AR, and the incorporation and oxidation of 14C-glucose were evaluated
      during 6 h of incubation. Results:  The results show that the BSA-V was superior
      to BSA-FAF and PVA in improving motility and AR. Viability was significantly
      increased (P < 0.05) by only BSA-V compared with PVA. When the main fatty acids
      compound of BSA-V were added to PVA, the sperm motility, viability and AR became
      almost the same as with BSA-V. The rate of incorporation and oxidation of 14C
      glucose were significantly increased (P < 0.05) by BSA-V compared with BSA-FAF
      and PVA. Fatty acids bound to BSA-V are important for improvement of sperm
      functions. Conclusions:  The present study postulates that fatty acids bound to
      BSA-V are important to acrosome reaction and the utilization of glucose in boar
      spermatozoa.

PMID- 29662407
TI  - Sexual activity in normal married couples in Japan: Investigation by
      questionnaire.
AB  - Aims:  After sildenafil, an inhibitor of type-5 phosphodiesterase (PDE5), was put
      on the Japanese market in March 1999 and then vardenafil emerged later in June
      2004, the diagnosis and therapy of erectile dysfunction (ED) has changed
      dramatically in Japan. However, there have been few studies in the meantime
      concerning the actual sexual activity in married couples. It has been almost
      impossible to understand and access the target(s), and the information regarding
      sex-life between couples in order to establish medical treatment for patients
      with ED. Methods:  In the present study, a questionnaire survey was carried out
      to examine the frequency, periodicity and foreseeability of sexual intercourse
      and other relevant matters in 300 married couples who had previously revealed
      that they had sexual intercourse once or more in 3 months. Results:  The results
      obtained clearly show that very few couples have sexual intercourse more than
      once when the opportunity of intercourse arises, and a majority of them had
      intercourse at night. Furthermore, the results indicated that more than 80% of
      the couples could not foresee sexual intercourse 30 min earlier. Conclusion:  It
      was concluded that drugs used to treat ED should be fast acting and make it
      possible to have sexual intercourse without feeling uncomfortable.

PMID- 29662408
TI  - Spermatogenesis in immature mammals.
AB  - Mammalian spermatogenesis has been studied extensively as a prime theme of male
      reproductive biology, especially for germ cell production, fertilization and
      development. Investigation of spermatogenesis has provided us with the
      opportunity to both study the male germ line stem cells and generate the
      transgenic animals. Spermatogenesis is conducted in the seminiferous tubules,
      which end in the rete testis. The organization of spermatogenesis means that the
      spermatogonia are uniformly distributed around the seminiferous tubules. The
      pubertal establishment and mature maintenance of spermatogenesis requires
      precursor cells. In bull testes at 4 weeks postnatal, gonocyte migration occurs
      and differentiated spermatogonia are recognized after 8 weeks. Within the period
      of 4-8 weeks of age, spermatogonial stem cell conversion and niche formation must
      occur. Spermatogonial stem cells are the only cells that can undergo self-renewal
      in spermatogenesis. Spermatogonial stem cell transplantation can potentially
      contribute to studies of gene expression during spermatogenesis and provide
      genetic progress in domestic animals. Bull spermatogonial stem cells have been
      demonstrated to be capable of colonizing recipient mouse seminiferous tubules.
      (Reprod Med Biol 2007; 6: 139-149).

PMID- 29662409
TI  - Role of vasoactive substances on endometrial and ovarian function.
AB  - In this review, it is proposed that the vasoactive agents endothelin (ET), nitric
      oxide (NO)/NO synthase (NOS) and carbon monoxide(CO)/heme oxygenase(HO) act
      directly on human endometrial functions and on ovarian functions in the normal
      menstrual cycle and in implantation periods. These vasoactive substances are
      likely to be important autocrine/paracrine factors that regulate a variety of
      physiological and pathological processes. The main actions of these agents are
      differentiation and implantation in the endometrial functions, and follicular
      growth, luteinization and atresia in the ovarian functions, in the tight
      connection between endometrial and ovarian systems during normal menstrual
      periods and during implantation (Reprod Med Biol 2007; 6: 157-164).

PMID- 29662410
TI  - Beneficial effect of long zona dissection on frozen-thawed blastocysts at a young
      age.
AB  - Aim:  To assess the appropriateness of assisted hatching using long zona
      dissection of human frozen-thawed blastocysts at the time of warming, especially
      in women over 35 years of age or with repeated implantation failures. Methods: 
      Of 177 frozen-thawed blastocyst transfer cycles, 89 control cycles had an intact
      zona and 88 cycles had assisted hatching using long zona dissection of human
      thawed blastocyst at the time of warming. These two groups were further
      subdivided by age to a total of four subgroups: <=34 years (assisted hatching, n
      = 39; controls, n = 39) and >=35 years (assisted hatching, n = 49; controls, n =
      50). Twenty-seven cycles in the control group and 28 cycles in the assisted
      hatching group had repeated implantation failures. The clinical and ongoing
      pregnancy rates and the implantation rate between the two groups were analyzed
      retrospectively. Results:  The clinical pregnancy and implantation rates in women
      <=34 years were significantly higher after the application of assisted hatching
      compared with the control group (87.2% and 71.2%vs 56.4% and 46.6%, P < 0.001).
      The clinical pregnancy and implantation rates of women with repeated implantation
      failures were higher after the application of assisted hatching compared with the
      control group (64.3% and 46.3%vs 48.1% and 34.1%), but this difference was not
      statistically significant. Conclusions:  Routine assisted hatching using long
      zona dissection at the time of warming on frozen-thawed blastocysts is a safe and
      easy method to perform and is extremely beneficial for increasing the pregnancy
      rate in young women <=34 years of age, but not in women >=35 years of age.
      Despite increased pregnancy and implantation rates in patients with repeated
      implantation failures, statistical significance was not achieved. (Reprod Med
      Biol 2007; 6: 211-218).

PMID- 29662411
TI  - Obstetric outcomes of elderly primiparous singleton pregnancies conceived by in
      vitro fertilization compared with those conceived spontaneously.
AB  - Aim:  To examine the obstetric outcomes of elderly primiparous singleton
      pregnancies conceived by in vitro fertilization (IVF) compared with those
      conceived spontaneously. Methods:  Data were collected from primiparous women
      aged 35 years and older with a singleton pregnancy conceived by IVF (n = 89) or
      spontaneously (n = 849). Data included antenatal data, gestational age at
      delivery, obstetric complications, such as pregnancy-induced hypertension,
      gestational diabetes, placental previa and placental abruption, mode of delivery,
      birth weight, fetal demise and the Apgar score at 1 min. Results:  The elective
      Cesarean rate in pregnancies following IVF was significantly higher than that in
      the control group (P = 0.014). However, there were no significant differences in
      obstetric outcomes between the two groups. Conclusions:  The current results did
      not support the IVF-related risks of elderly primiparous singleton pregnancies.
      (Reprod Med Biol 2007; 6: 219-222).

PMID- 29662412
TI  - Cryoprotective effects of various saccharides on cryopreserved mouse sperm from
      various strains.
AB  - Aim:  Cryopreservation of mouse sperm commonly uses raffinose, which is a
      trisaccharide, plus 3% skim milk. Because of the present lack of knowledge of the
      effectiveness of any other saccharides, we examined the cryoprotective effects of
      various saccharides on the viability of mouse sperm from various strains to
      determine which saccharides are the best cryoprotectants for mouse sperm.
      Methods:  Sperm from the caudae epididymides of mature C57BL/6J mice were frozen
      with monosaccharides (fructose, glucose, rhamnose, xylose), disaccharides
      (lactose, maltose, sucrose, trehalose) or trisaccharides (melezitose, raffinose)
      in a range of concentrations (4-33%). After thawing, the optimal concentration
      was determined to be the concentration in which there was the highest proportion
      of motile sperm. In addition, sperm of inbred and hybrid mice were frozen with
      the saccharides at the optimal concentrations and used for in vitro
      fertilization. Results:  The optimal concentration was 12% for the disaccharides
      and 18% for the trisaccharides. The fertility of all strains, except C57BL/6J,
      showed the best cryoprotective effects with maltose, melezitose and raffinose
      when compared with fresh sperm. Conclusion:  Maltose, melezitose and raffinose
      have the best effects when used as a protectant for cryopreservation of mouse
      sperm. (Reprod Med Biol 2007; 6: 229-233).

PMID- 29662414
TI  - Anticoagulant therapy and pregnancy.
AB  - Low dose aspirin therapy is one of the anticoagulant treatments used during
      pregnancy. Anticoagulant agents may be useful for several disorders, such as
      recurrent miscarriage, pre-eclampsia, fetal growth restriction and infertility.
      However, it is unclear whether anticoagulant therapy can increase the live birth
      rate in all of these cases. Recent data suggest that a low-dose aspirin and
      heparin combination therapy is effective in the prevention of recurrent pregnancy
      loss in women with antiphospholipid syndrome. Thrombogenic diseases, for example,
      protein C deficiency, protein S deficiency, factor XII deficiency and
      hyperhomocysteinemia, may cause pregnancy loss. The etiology of recurrent
      miscarriage is often unclear and may be multifactorial, with much controversy
      regarding diagnosis and treatment. Although 70% of recurrent pregnancy losses are
      unexplained, anticoagulant therapy is effective in maintaining pregnancy without
      antiphospholipid antibody syndrome. We conclude that a low-dose aspirin and
      heparin combination therapy can be useful for unexplained cases of recurrent
      pregnancy loss without antiphospholipid antibody syndrome. (Reprod Med Biol 2008;
      7: 1-10).

PMID- 29662415
TI  - Regulation of human luteinizing hormone receptor in the ovary.
AB  - The luteinizing hormone receptor (LHR) is essential for elevated levels of
      progesterone to maintain pregnancy during the first trimester; the maintenance of
      the expression of LHR is a key factor controlling the duration of luteal
      function. Therefore, as the expression of LHR is most likely to be regulated by
      the stability of the receptor mRNA at the luteal phase of the human menstrual
      cycle, we focused on studies examining the stability of mRNA rather than the
      production of mRNA. In addition, LHR (exon 9), one of the splice variants of
      human LHR (hLHR), was cloned in the corpus luteum of a patient with a regular
      menstrual cycle. The results of Western blots using Percoll gradient
      fractionation indicated that hLHR formed complexes with hLHR (exon 9), which are
      transferred to the lysosome, where they are eventually degraded, instead of being
      translocated from the endoplasmic reticulum to the transducing organelle. These
      results showed that hLHR (exon 9) caused a reduction in the expression of
      functional receptor number and affected the signaling condition of wild-type
      hLHR. As the luteal phase progressed hLHR (exon 9) increased relative to hLHR,
      demonstrating that hLHR (exon 9) was expressed more than hLHR in the late luteal
      phase. This work reveals the essential function of the regulatory and structural
      elements involved in human LH receptor splicing, and that hLHR (exon 9) can
      negatively control the function of wild-type receptors. Moreover, this finding
      presented a novel mechanism of regulation of LHR in the human corpus luteum.
      (Reprod Med Biol 2008; 7: 11-16).

PMID- 29662416
TI  - p-Chloroamphetamine-induced rat ejaculation is not associated with the preoptic
      nucleus or medial nucleus amygdala.
AB  - Aim:  In the rat, intraperitoneal injection of p-chloroamphetamine (PCA), which
      releases central 5-hydroxytryptamine (5-HT) from serotonergic nerve terminals,
      induces ejaculation, even in the absence of an estrus female or female-related
      smell information. It is well known that the medial preoptic nucleus (MPN) and
      the medial nucleus amygdala (MEA) play a major role in the control of male sexual
      behavior in mammals. We examined whether or not neuronal activity of the MPN
      and/or the MEA was associated with PCA-induced ejaculation. Methods:  Using c-Fos
      immunohistochemistry, we demonstrated a difference in the neural activities of
      the MPN and the MEA for ejaculation during copulation with an estrus female and
      ejaculation by PCA injection. Results:  Increased numbers of c-Fos-immunoreactive
      (c-Fos-IR) cells were found in the MPN and the MEA in the brains of the mating
      animals, whereas in the brains of the animals undergoing PCA-induced ejaculation
      there was no increase in the number of c-Fos-IR cells in the MPN and a small
      increase in the MEA. Conclusion:  Based on these results, ejaculation induced by
      PCA is not associated with the MPN. Moreover, the MEA is not the main act for
      this ejaculation. (Reprod Med Biol 2008; 7: 37-43).

PMID- 29662417
TI  - Effect of total cholesterol, glucose and blood urea nitrogen on embryo quality in
      post-partum superovulated suckling Japanese Black cattle.
AB  - Aim:  This study was conducted to examine the effect of blood metabolites on
      embryo quality in post-partum suckling Japanese Black cattle. Methods:  Blood
      samples were taken from 23 cows 30 days before, at and 30 days after parturition.
      Cows were synchronized 40 or 41 days after calving (day 0) and divided into three
      groups: control (n = 6), gonadotropin-releasing hormone ([GnRH]n = 10) and
      estradiol benzoate ([EB]n = 7). All groups received a controlled internal drug
      release (CIDR) device intravaginally together with 2 mg EB i.m. on day 0 and
      superovulation was induced in all groups from days 5-7 with a gradually
      decreasing dose of follicle-stimulating hormone (FSH). Two milligrams of EB was
      given on day 8 and GnRH (0.1 mg) was given on day 9 of insertion of the CIDR in
      the EB and GnRH groups. Cows were inseminated twice after the onset of estrus and
      embryos were recovered 7-8 days after artificial insemination. Results:  The
      number of corpus luteum detected by ultrasonography in the EB group was
      significantly higher (P < 0.05) than that in the GnRH group. The number and rate
      of transferable and freezable embryos did not differ significantly among the
      groups. Regardless of the treatments, the total cholesterol level from
      parturition until 30 days after parturition was significantly higher (P < 0.01)
      in the good category than in the poor category of cows. Conclusions:  The number
      of transferable embryos produced by post-partum superovulated suckling Japanese
      Black cattle was affected by the level of total cholesterol from parturition
      until 30 days after parturition. Moreover, administration of EB in CIDR-treated
      cows increased the numbers of corpus luteum and yielded better rates of
      transferable and freezable embryos. (Reprod Med Biol 2008; 7: 55-62).

PMID- 29662419
TI  - A physiological role of contractions in hatched mouse blastocysts.
AB  - Purpose: Using mouse blastocysts with implantation delayed for 7 days (dormant
      blastocysts) and time-lapse videomicrography, we examined the physiological role
      of contractions in hatched blastocysts. Methods: The degree and number of
      contractions in dormant blastocysts were analyzed in images recorded for 48 h of
      culture, and compared with those in dormant blastocysts in which implantation was
      induced (activated blastocysts), and dormant blastocysts cultured with estrogen
      or progesterone. Results: Activated blastocysts exhibited a significantly smaller
      number of weak contractions and a significantly larger number of strong
      contractions, compared with dormant blastocysts. Furthermore, the numbers of weak
      and strong contractions in dormant blastocysts cultured with estradiol-17beta
      were significantly less frequent or more frequent than those in dormant
      blastocysts cultured with progesterone and those cultured without steroids.
      Expression of estrogen receptor mRNA was also detected in dormant blastocysts by
      the method of reverse transcription-polymerase chain reaction. Conclusion: These
      results suggested that activated blastocysts enhance the contractions as a
      preparation for the implantation, and that the enhanced contractions in those
      serve as a physical stimulation for maternal recognition of pregnancy.

PMID- 29662418
TI  - Elective cryopreservation of all day 5 blastocysts is more effective than using
      day 6 blastocysts for improving pregnancy outcome in stimulated cycles.
AB  - Aim:  To evaluate the efficacy of cryopreservation of all blastocysts for future
      transfers in stimulated cycles. Methods:  We carried out fresh blastocyst
      transfer cycles on day 5 (n = 290) or day 6 (n = 119) and thawed blastocyst
      transfer cycles that were frozen on day 5 (n = 136), day 6 (n = 71) or day 6
      electively (n = 21). We retrospectively compared the clinical outcome of fresh
      blastocyst transfers with thawed blastocyst transfers according to the day of
      blastocyst transfer or freezing. Results:  The clinical implantation rates in
      women with stimulated cycles were significantly higher after the transfer of
      thawed blastocysts compared with the transfer of fresh blastocysts (day 5, P <
      0.0005; day 6, P < 0.00005). Although the implantation rate of fresh day 6
      transfer cycles was lower than that of elective day 6 frozen-thawed cycles, this
      difference was not statistically significant (P = 0.17). Conclusions:  Thawed
      blastocysts demonstrated a better potential for implantation when compared with
      fresh blastocysts in stimulated cycles. We concluded that elective
      cryopreservation of all blastocysts on day 5 is an effective option to improve
      the clinical outcome in stimulated cycles. Additionally, with cryopreservation of
      all day 6 blastocysts, the implantation rates of first embryo transfers may
      increase by allowing the best-quality blastocysts to be transferred in thawed
      cycles. (Reprod Med Biol 2008; 7: 75-83).

PMID- 29662420
TI  - Fatty acid composition of lipids in day 7-13 blastocysts, serum and uterine fluid
      of rabbits.
AB  - Purpose: The fatty acid composition of rabbit blastocysts, blood serum and
      uterine fluids were analyzed to study embryonic lipid metabolism. Methods:
      Embryos were collected from Japanese white rabbits and fatty acids were analyzed
      by gas chromatograph. Results: Total amount of fatty acids in blastocysts was
      higher than that in serum and uterine fluid. The amount of fatty acids in
      blastocysts markedly decreased during days 7-13 of pregnancy, and in serum had
      hovered, but in uterine fluid on day 13 was nine times higher than that on day 7
      of pregnancy. Palmitic acid predominates in blastocysts, serum and uterine fluid
      during this period. Conclusion: Palmitic acid is the most abundant fatty acid in
      the blastocysts, serum and uterine fluids of rabbit during days 7-13 of
      pregnancy.

PMID- 29662421
TI  - Individual fertility differences in the frozen-thawed spermatozoa among semen
      donors in the Labrador Retriever.
AB  - Purpose: We aimed to validate and determine the possible application of
      transcervical insemination of frozen semen for improved breeding in guide dogs
      for the blind in Japan. Methods: From February 2004 to March 2007, a total of 53
      Labrador Retriever bitches, used for the breeding of guide dogs for the blind,
      were transcervically inseminated with frozen-thawed semen from 13 males by means
      of a cystoscope. Results: The overall whelping and pregnancy rate with the frozen
      semen was 42%. Pregnancy rates ranged widely from 0 to 100% depending on the
      semen donor male. Of 13 males, 6 males exhibited severely poor fertility (less
      than 20% pregnancy rate) and 3 males exhibited high fertility (over 70% pregnancy
      rate) on artificial insemination. However, the spermatozoa motility after thawing
      was not significantly different among these dogs. In addition, heterospermic
      insemination revealed the optimal timing for transcervical insemination with
      frozen-thawed semen to be by day 6 after the LH surge. Conclusions: Although
      transcervical insemination of frozen-thawed semen is effective for breeding of
      guide dogs for the blind, some modification of freeze-thawing procedures might be
      required to overcome individual fertility differences in the frozen-thawed
      spermatozoa among semen donor dogs,. In addition, the motility of spermatozoa
      after thawing might not be an appropriate indicator of the relative fertility of
      frozen-thawed spermatozoa in dogs.

PMID- 29662422
TI  - Autoantibodies and coagulation in reproductive medicine.
AB  - Management of recurrent pregnancy loss (RPL) is considered to be difficult, in
      part because of cunfusion between autoantibodies and coagulation disorders.
      Autoantibodies and coagulation are related; two groups of multicenter studies
      concerning autoantibodies and coagulation reported that factor XII deficiency,
      hypofibrinolysis, anti-phosphatidylethanolamine (aPE), anti-beta2-glycoprotein I,
      anti-annexin A5, and lupus anticoagulant (LA) were found to be frequent risk
      factors in RPL women. Therefore, discrimination of autoantibodies and coagulation
      is important in understanding RPL well. We propose three types of pathways
      regarding reproduction, which are different and independent: (1) Negatively
      charged-phospholipid related antibodies (anti-phosphatidylserine; aPS, anti
      cardiolipin; aCL, lupus anticoagulant; LA, anti-annexin A5; aANX), (2) factor XII
      aPE-fibrinolysis: suppression of fibrinolysis, (3) protein C-protein S-factor V:
      loss of inactivation against activated factor V. Women with RPL and infertility
      showed similar findings in terms of the above clinical tests. Available data,
      however, is not enough to conclude whether these are pathogenic to infertile
      women.

PMID- 29662423
TI  - Interprofessional team approach to infertility treatment in Japan.
AB  - Purpose: At present, a team approach involving gynecologists, nurses,
      embryologists, and the other professionals is considered necessary to provide
      successful infertility treatment. First, we documented which professionals were
      in charge during various phases of infertility treatment. Second, clinical staff
      and patients were surveyed regarding their expectations regarding which of these
      professionals should contribute during examination, during treatment and after
      treatment for infertility. Methods: We surveyed the actual situation perceived by
      staff as well as the desired situation for staff and patients in relation to 21
      procedures related to infertility treatment. We distributed 781 questionnaires to
      staff and patients at 86 facilities. Of 380 returned by mail, we analyzed 128
      responses from staff who worked with four types of professionals or specialists,
      i.e., medical doctors, nurses, embryologists, and medical clerks, and 46 from
      patients who consulted these professionals during their treatment. Results: Most
      staff recognized 5 of 15 procedures before and after treatment as being conducted
      by medical doctors alone. However, explanation and consultation regarding the
      methods and schedule were mainly performed with an interprofessional team
      approach. Expectations regarding professionals in charge differed between staff
      and patients. A team approach including infertility counselors and medical clerks
      was utilized and considered desirable during counseling. Conclusions: An
      effective team approach should be established for each step of infertility
      treatment.

PMID- 29662424
TI  - Poor pregnancy outcome following assisted reproductive technology among women
      operated on for bilateral endometriomas.
AB  - Purpose: To determine the first line of infertility treatment for managing
      patients with unilateral or bilateral ovarian endometriomas. Methods: We
      evaluated pregnancy outcome in patients who had received ovarian surgery for
      unilateral (Group U, n = 47) or bilateral endometriomas (Group B, n = 38) and
      aspiration with or without alcohol fixation for unilateral (Group u, n = 37) or
      bilateral endometriomas (Group b, n = 22). Subsequently, 64 of these women,
      excluding 29 dropouts, underwent assisted reproductive technology. We compared
      the clinical pregnancy rates of the four groups. Results: The cumulative
      pregnancy rate after operation of Group B (18%) was significantly lower than that
      of a cyst-free control group (n = 143; 44%) and Group U (43%). Group B had fewer
      oocytes fertilized during ART than did Group b (P < 0.005) and fewer blastocysts
      available for transfer (P < 0.005). The cumulative pregnancy rate of Group B was
      also lower than in Group b (P = 0.052). Conclusions: Pregnancy outcomes of Group
      B were not better than for Group b. Therefore, encouraging such women to move
      directly to ART might help avoid ovarian damage and improve their ability to
      achieve a pregnancy.

PMID- 29662425
TI  - Effect of preantral mouse follicle culture period on meiotic maturation and
      developmental competence of oocytes.
AB  - Purpose: The aim of this study is to determine the optimal culture period for
      meiotic maturation and developmental competence of in vitro-grown mouse oocytes.
      Methods: Early preantral follicles with diameter of 100-130 MUm were collected
      mechanically from day 14 mouse ovaries and cultured for 8, 10, and 12 days. The
      diameters of follicles and oocytes were measured, and chromatin configuration in
      oocytes was observed. We also examined meiotic maturation by human chorionic
      gonadotropin (hCG)/epidermal growth factor (EGF) stimulation, developmental
      competence of fertilized oocytes to blastocysts, and apoptosis in blastocysts.
      Results: The follicular diameter increased significantly from days 4 to 10, and
      the diameter of day 12 oocytes was significantly larger than day 8 or earlier
      oocytes. Chromatin configuration around the nucleolus was transformed from
      "nonsurrounded (immature)" to "surrounded (mature)" after 10 days. Furthermore,
      MII rate of day 10 and 12 oocytes was significantly higher than that of day 8
      oocytes. The blastocyst rate of day 10 oocytes was higher than that of day 8 or
      12 oocytes. The blastocyst apoptotic rate of day 12 oocytes was higher than that
      of day 10 oocytes. Conclusions: Long culture periods of in vitro-grown oocytes
      affect meiotic maturation, developmental competence to blastocysts, and
      apoptosis.

PMID- 29662426
TI  - Recombinant follicle-stimulating hormone (follitropin alfa) for ovulation
      induction in Japanese patients with anti-estrogen-ineffective oligo- or
      anovulatory infertility: results of a phase II dose-response study.
AB  - Purpose: To determine the optimal regimen of recombinant human follicle
      stimulating hormone (r-hFSH) for ovulation induction (OI) in Japanese women with
      amenorrhea I or anovulatory infertility. Methods: In this randomized, double
      blind, dose-finding study, women aged 20-39 years were enrolled. Patients
      underwent a chronic low-dose step-up regimen with starting doses of r-hFSH of
      37.5 IU (group L; n = 62), 75 IU (group M; n = 62) or 150 IU (group H; n = 60).
      Primary endpoint was time to achieve a dominant follicle with mean diameter >=18
      mm. Secondary endpoints included percentage of patients producing a dominant
      follicle >=18 mm, achieving ovulation, and biochemical pregnancy. Results: Median
      time to achieve a dominant follicle >=18 mm was 14 days (group L; 87.7%), 10 days
      (group M; 98.4%), and 8 days (group H; 94.5%). In group M, ovulation occurred in
      95.1% of patients, with pregnancy in 18.0%, compared with 86.0% and 15.8% in
      group L, and 50.9% and 9.1% in group H, respectively. Twelve patients developed
      ovarian hyperstimulation syndrome (nine in group H). Most adverse events in
      groups L and M were mild in severity. Conclusions: A starting dose of 75 IU r
      hFSH was associated with a favorable efficacy and safety profile for OI in
      Japanese women.

PMID- 29662427
TI  - Evaluation of possible criteria for elective single embryo transfer.
AB  - Purpose: A major problem of assisted reproductive technology (ART) is multiple
      gestation, which impacts neonatal and perinatal medicine. The literature contains
      a number of reports that elective single embryo transfer (eSET) is effective for
      the control of multiple pregnancies; however, to date, uniform criteria have not
      been established. Methods: Using logistic regression analysis based on the
      results of ART in our department from January 2005 to July 2006, our eSET
      criteria were established. We conducted a comparative study of the clinical
      pregnancy rate, multiple gestation rate, and delivery rate before and after eSET
      (before-eSET and after-eSET groups, respectively). Results: As a result of the
      analysis, our eSET criteria included all three of the following: (A) patient age
      <=37, (B) previous IVF/ICSI trials <=5, and (C) acquisition of two or more good
      quality embryos. Based on our criteria, the after-eSET group was not found to
      have a decrease in the pregnancy rate; however, the multiple gestation rate
      decreased as compared to the before-eSET group. In addition, as a result of
      various evaluations of the eSET group, interesting findings were revealed.
      Conclusions: In the after-eSET group, our eSET criteria achieved a decrease in
      the multiple pregnancy rate without a decrease in the pregnancy rate.

PMID- 29662428
TI  - Vitrification of canine cumulus-oocyte complexes in DAP213 with a cryotop holder.
AB  - Purpose: The effects of the cryoprotectant and the container (holder) used for
      the vitrification of canine germinal vesicle stage oocytes were examined to
      improve the cryopreservation method for canine oocytes and embryos. Methods:
      Canine cumulus-oocyte complexes (COCs) were collected from ovaries, and were
      vitrified with E30S (30% ethylene glycol and 0.5 M sucrose) or DAP213 (2 M
      dimethyl sulfoxide, 1 M acetamide, and 3 M propylene glycol) solution held by a
      cryotube or cryotop sheets. After warming, the oocytes were stained with
      propidium iodide for the assessment of their plasma membrane integrity. Results:
      In all the vitrification groups, more than 65% of the vitrified oocytes displayed
      a normal morphology (E30S-top, 65.6%; DAP-tube, 67.3%; DAP-top, 80.0%). However,
      when assessed by propidium iodide staining, the viability of oocytes in the DAP
      top group (43.6%) was higher than that in the E30S-top group (21.3%, P < 0.05).
      Furthermore, the viability of the oocytes in the DAP-top group (43.6%) was higher
      than that in the DAP-tube group (4.1%, P < 0.05). Conclusions: These results
      suggest that a combination of DAP213 as the cryoprotectant and a cryotop sheet as
      the holder improved viability after the vitrification of canine oocytes at the
      germinal vesicle stage.

PMID- 29662429
TI  - Mullerian duct cyst: a curable entity of male infertility. Two case reports.
AB  - Purpose: Mullerian duct cyst is a rudiment of a Mullerian duct in the fetal
      period which causes ejaculatory duct obstruction and male infertility. Case
      report: We report two patients with Mullerian duct cyst that presented with low
      ejaculate volume, oligoasthenoteratozoospermia and azoospermia syndrome.
      Transrectal ultrasound (TRUS) and magnetic resonance image (MRI) revealed a
      midline prostatic cystic structure. In each case, we performed a TRUS guided
      transperineal aspiration of the cyst. Seminograms of the patients improved and
      one of their wives got spontaneously pregnant 3 months after the surgery.
      Conclusion: We should assume the TRUS guided aspiration of Mullerian duct cyst.

PMID- 29662430
TI  - Rules infants look by: Testing the assumption of transitivity in visual salience.
AB  - What drives infants' attention in complex visual scenes? Early models of infant
      attention suggested that the degree to which different visual features were
      detectable determines their attentional priority. Here, we tested this by asking
      whether two targets - defined by different features, but each equally salient
      when evaluated independently - would drive attention equally when pitted head-to
      head. In Experiment 1, we presented 6-month-old infants with an array of gabor
      patches in which a target region varied either in color or spatial frequency from
      the background. Using a forced-choice preferential-looking method, we measured
      how readily infants fixated the target as its featural difference from the
      background was parametrically increased. Then, in Experiment 2, we used these
      psychometric preference functions to choose values for color and spatial
      frequency targets that were equally salient (preferred), and pitted them against
      each other within the same display. We reasoned that, if salience is transitive,
      then the stimuli should be iso-salient and infants should therefore show no
      systematic preference for either stimulus. On the contrary, we found that infants
      consistently preferred the color-defined stimulus. This suggests that computing
      visual salience in more complex scenes needs to include factors above and beyond
      local salience values.

PMID- 29662431
TI  - The Neuroprotective Effects of Thymoquinone: A Review.
AB  - Thymoquinone (TQ), one of the main components active of Nigella sativa, exhibited
      very useful biomedical effects such as anti-inflammatory, antioxidant,
      antimicrobial, antiparasitic, anticancer, hypoglycemic, antihypertensive, and
      antiasthmatic effects. There are several studies about pharmacological activities
      of TQ but its neuroprotection effects are not fully described. The literature
      search has indicated many studies pertaining to the effects of TQ in neurological
      problems such as epilepsy, parkinsonism, anxiety, and improvement of learning and
      memory, and so on. In addition, TQ protected brain cells from various injuries
      due to its antioxidant, anti-inflammatory, and apoptotic effects in cell line and
      experimental animal models. The present study has been designed to review the
      scientific literature about the pharmacological activities of TQ to the
      neurological diseases. This study purposed that although experimental studies
      indicated the beneficial effects of TQ against nervous system problems, better
      designed clinical trials in humans are needed to confirm these effects.

PMID- 29662432
TI  - Frontal Brain Asymmetry and Willingness to Pay.
AB  - Consumers frequently make decisions about how much they are willing to pay (WTP)
      for specific products and services, but little is known about the neural
      mechanisms underlying such calculations. In this study, we were interested in
      testing whether specific brain activation-the asymmetry in engagement of the
      prefrontal cortex-would be related to consumer choice. Subjects saw products and
      subsequently decided how much they were willing to pay for each product, while
      undergoing neuroimaging using electroencephalography. Our results demonstrate
      that prefrontal asymmetry in the gamma frequency band, and a trend in the beta
      frequency band that was recorded during product viewing was significantly related
      to subsequent WTP responses. Frontal asymmetry in the alpha band was not related
      to WTP decisions. Besides suggesting separate neuropsychological mechanisms of
      consumer choice, we find that one specific measure-the prefrontal gamma asymmetry
      was most strongly related to WTP responses, and was most coupled to the actual
      decision phase. These findings are discussed in light of the psychology of WTP
      calculations, and in relation to the recent emergence of consumer neuroscience
      and neuromarketing.

PMID- 29662433
TI  - Palmitoylethanolamide Ameliorates Hippocampal Damage and Behavioral Dysfunction
      After Perinatal Asphyxia in the Immature Rat Brain.
AB  - Perinatal asphyxia (PA) is an obstetric complication associated with an impaired
      gas exchange. This health problem continues to be a determinant of neonatal
      mortality and neurodevelopmental disorders. Palmitoylethanolamide (PEA) has
      exerted neuroprotection in several models of brain injury and neurodegeneration.
      We aimed at evaluating the potential neuroprotective role of PEA in an
      experimental model, which induces PA in the immature rat brain. PA was induced by
      placing Sprague Dawley newborn rats in a water bath at 37 degrees C for 19 min.
      Once their physiological conditions improved, they were given to surrogate
      mothers that had delivered normally within the last 24 h. The control group was
      represented by non-fostered vaginally delivered pups, mimicking the clinical
      situation. Treatment with PEA (10 mg/kg) was administered within the first hour
      of life. Modifications in the hippocampus were analyzed with conventional
      electron microscopy, immunohistochemistry (for NeuN, pNF-H/M, MAP-2, and GFAP)
      and western blot (for pNF H/M, MAP-2, and GFAP). Behavior was also studied
      throughout Open Field (OF) Test, Passive Avoidance (PA) Task and Elevated Plus
      Maze (EPM) Test. After 1 month of the PA insult, we observed neuronal nucleus
      degeneration in CA1 using electron microscopy. Immunohistochemistry revealed a
      significant increase in pNF-H/M and decrease in MAP-2 in CA1 reactive area. These
      changes were also observed when analyzing the level of expression of these
      markers by western blot. Vertical exploration impairments and anxiety-related
      behaviors were encountered in the OF and EPM tests. PEA treatment attenuated PA
      induced hippocampal damage and its corresponding behavioral alterations. These
      results contribute to the elucidation of PEA neuroprotective role after PA and
      the future establishment of therapeutic strategies for the developing brain.

PMID- 29662434
TI  - Review of the Neural Oscillations Underlying Meditation.
AB  - Objective: Meditation is one type of mental training that has been shown to
      produce many cognitive benefits. Meditation practice is associated with
      improvement in concentration and reduction of stress, depression, and anxiety
      symptoms. Furthermore, different forms of meditation training are now being used
      as interventions for a variety of psychological and somatic illnesses. These
      benefits are thought to occur as a result of neurophysiologic changes. The most
      commonly studied specific meditation practices are focused attention (FA), open
      monitoring (OM), as well as transcendental meditation (TM), and loving-kindness
      (LK) meditation. In this review, we compare the neural oscillatory patterns
      during these forms of meditation. Method: We performed a systematic review of
      neural oscillations during FA, OM, TM, and LK meditation practices, comparing
      meditators to meditation-naive adults. Results: FA, OM, TM, and LK meditation are
      associated with global increases in oscillatory activity in meditators compared
      to meditation-naive adults, with larger changes occurring as the length of
      meditation training increases. While FA and OM are related to increases in
      anterior theta activity, only FA is associated with changes in posterior theta
      oscillations. Alpha activity increases in posterior brain regions during both FA
      and OM. In anterior regions, FA shows a bilateral increase in alpha power, while
      OM shows a decrease only in left-sided power. Gamma activity in these meditation
      practices is similar in frontal regions, but increases are variable in parietal
      and occipital regions. Conclusions: The current literature suggests distinct
      differences in neural oscillatory activity among FA, OM, TM, and LK meditation
      practices. Further characterizing these oscillatory changes may better elucidate
      the cognitive and therapeutic effects of specific meditation practices, and
      potentially lead to the development of novel neuromodulation targets to take
      advantage of their benefits.

PMID- 29662435
TI  - Ac2-26 Induces IKKbeta Degradation Through Chaperone-Mediated Autophagy Via HSPB1
      in NCM-Treated Microglia.
AB  - Annexin A1 (ANXA1) is an endogenous protein with potent anti-inflammatory
      properties in the brain. Although ANXA1 has been predominantly studied for its
      binding to formyl peptide receptors (FPRs) on plasma membranes, little is known
      regarding whether this protein has an anti-inflammatory effect in the cytosol.
      Here, we investigated the mechanism by which the ANXA1 peptide Ac2-26 decreases
      high TNF-alpha production and IKKbeta activity, which was caused by oxygen
      glucose deprivation/reperfusion (OGD/R)-induced neuronal conditioned medium (NCM)
      in microglia. We found that exogenous Ac2-26 crosses into the cytoplasm of
      microglia and inhibits both gene expression and protein secretion of TNF-alpha.
      Ac2-26 also causes a decrease in IKKbeta protein but not IKKbeta mRNA, and this
      effect is inverted by lysosome inhibitor NH4CL. Furthermore, we demonstrate that
      Ac2-26 induces IKKbeta accumulation in lysosomes and that lysosomal-associated
      membrane protein 2A (LAMP-2A), not LC-3, is enhanced in microglia exposed to Ac2
      26. We hypothesize that Ac2-26 mediates IKKbeta degradation in lysosomes through
      chaperone-mediated autophagy (CMA). Interestingly, ANXA1 in the cytoplasm does
      not interact with IKKbeta but with HSPB1, and Ac2-26 promotes HSPB1 binding to
      IKKbeta. Furthermore, both ANXA1 and HSPB1 can interact with Hsc70 and LAMP-2A,
      but IKKbeta only associates with LAMP-2A. Downregulation of HSPB1 or LAMP-2A
      reverses the degradation of IKKbeta induced by Ac2-26. Taken together, these
      findings define an essential role of exogenous Ac2-26 in microglia and
      demonstrate that Ac2-26 is associated with HSPB1 and promotes HSPB1 binding to
      IKKbeta, which is degraded by CMA, thereby reducing TNF-alpha expression.

PMID- 29662437
TI  - Ketogenic Diet Improves Brain Ischemic Tolerance and Inhibits NLRP3 Inflammasome
      Activation by Preventing Drp1-Mediated Mitochondrial Fission and Endoplasmic
      Reticulum Stress.
AB  - Background: Neuroprotective effects of ketogenic diets (KD) have been reported in
      stroke models, and nucleotide-binding domain (NOD)-like receptor protein 3
      (NLRP3) inflammasome has also been implicated in the pathogenesis of stroke. This
      study aimed to investigate the effects of KD on NLRP3 inflammasome and explore
      the potential molecular mechanisms. Methods: In in vivo study, mice were fed with
      KD for 3 weeks and then subjected to middle cerebral artery occlusion/reperfusion
      (MCAO/R)-injury. In in vitro study, SH-SY-5Y cells were treated with beta
      hydroxybutyrate (BHB) followed by oxygen-glucose deprivation/reoxygenation
      (OGD/R). NLRP3 inflammasome activation and related regulatory mechanisms were
      evaluated. Results: Mice fed with KD had increased tolerance to MCAO/R. KD
      inhibited endoplasmic reticulum (ER) stress and suppressed TXNIP/NLRP3
      inflammasome activation in the brain. The in vitro study showed BHB (10 mM)
      prevented the mitochondrial translocation of dynamin-related protein 1 (Drp1) to
      inhibit mitochondrial fission. Furthermore, BHB decreased reactive oxygen species
      (ROS) generation, inhibited ROS-NLRP3 pathway in OGD/R-treated cells, and
      suppressed ER stress-induced NLRP3 inflammasome activation. Conclusions: KD may
      suppress ER stress and protect mitochondrial integrity by suppressing the
      mitochondrial translocation of Drp1 to inhibit NLRP3 inflammasome activation,
      thus exerting neuroprotective effects. Our findings provide evidence for the
      potential application of KD in the prevention of ischemic stroke.

PMID- 29662438
TI  - Cannabinoid Receptor Type 1 Expression in the Developing Avian Retina:
      Morphological and Functional Correlation With the Dopaminergic System.
AB  - The avian retina has been used as a model to study signaling by different neuro-
      and gliotransmitters. It is unclear how dopaminergic and cannabinoid systems are
      related in the retina. Here we studied the expression of type 1 and 2 cannabinoid
      receptors (CB1 and CB2), as well as monoacylglycerol lipase (MAGL), the enzyme
      that degrades 2-arachidonoylglycerol (2-AG), during retina development. Our data
      show that CB1 receptor is highly expressed from embryonic day 5 (E5) until post
      hatched day 7 (PE7), decreasing its levels throughout development. CB1 is densely
      found in the ganglion cell layer (GCL) and inner plexiform layer (IPL). CB2
      receptor was also found from E5 until PE7 with a decrease in its contents from E9
      afterwards. CB2 was mainly present in the lamination of the IPL at PE7. MAGL is
      expressed in all retinal layers, mainly in the IPL and OPL from E9 to PE7 retina.
      CB1 and CB2 were found both in neurons and glia cells, but MAGL was only
      expressed in Muller glia. Older retinas (PE7) show CB1 positive cells mainly in
      the INL and co-expression of CB1 and tyrosine hydroxylase (TH) are shown in a few
      cells when both systems are mature. CB1 co-localized with TH and was heavily
      associated to D1 receptor labeling in primary cell cultures. Finally, cyclic AMP
      (cAMP) was activated by the selective D1 agonist SKF38393, and inhibited when
      cultures were treated with WIN55, 212-2 (WIN) in a CB1 dependent manner. The
      results suggest a correlation between the endocannabinoid and dopaminergic
      systems (DSs) during the avian retina development. Activation of CB1 limits cAMP
      accumulation via D1 receptor activation and may influence embryological
      parameters during avian retina differentiation.

PMID- 29662439
TI  - Chondroitin Sulfate Expression in Perineuronal Nets After Goldfish Spinal Cord
      Lesion.
AB  - Perineuronal nets (PNNs) surrounding neuronal cell bodies regulate neuronal
      plasticity during development, but their roles in regeneration are unclear. In
      the PNNs, chondroitin sulfate (CS) is assumed to be involved in inhibiting
      contact formation. Here, we examined CS expression in PNNs in the ventral horn of
      a goldfish hemisected spinal cord in which descending axons regenerate beyond the
      lesion to connect with distal spinal neurons. In intact fish, chondroitin sulfate
      A (CS-A)-positive PNNs accounted for 5.0% of HuC/D-immunoreactive neurons, and
      48% of choline acetyltransferase (ChAT)-immunoreactive neurons. At 2, 4 and 8
      weeks after spinal hemisection, CS-A-positive PNNs accounted for 8.4%-9.9% of
      HuC/D-immunoreactive neurons, and 50%-60% of ChAT-immunoreactive neurons, which
      was not significantly different from intact fish. Chondroitin sulfate C (CS-C)
      positive PNNs accounted for 6.4% of HuC/D-immunoreactive neuron, and 67% of ChAT
      immunoreactive neurons in intact fish. At 2, 4 and 8 weeks after spinal
      hemisection, CS-C-positive PNNs accounted for 7.9%, 5.5% and 4.3%, respectively,
      of HuC/D-immunoreactive neurons, and 65%, 52% and 42%, respectively, of ChAT
      immunoreactive neurons, demonstrating a significant decrease at 4 and 8 weeks
      after spinal hemisection. Among ventral horn neurons that received descending
      axons labeled with tetramethylrhodamine dextran amine (RDA) applied at the level
      of the first spinal nerve, CS-A-positive PNNs accounted for 53% of HuC/D
      immunoreactive neurons. At 2 and 4 weeks after spinal hemisection, CS-A-positive
      PNNs accounted for 57% and 56% of HuC/D-immunoreactive neurons, which was not
      significantly different from intact fish. CS-C-positive PNNs, accounted for 48%
      of HuC/D-immunoreactive neurons that received RDA-labeled axons. At 2 and 4 weeks
      after spinal hemisection, CS-C-positive PNNs significantly decreased to 22% of
      the HuC/D-immunoreactive neurons, and by 4 weeks after spinal hemisection they
      had returned to 47%. These findings suggest that CS expression is maintained in
      the PNNs after spinal cord lesion, and that the descending axons regenerate to
      preferentially terminate on neurons not covered with CS-C-positive PNNs.
      Therefore, CS-C in the PNNs possibly inhibits new contact with descending axons,
      and plasticity in the spinal neurons might be endowed by downregulation of CS-C
      in the PNNs in the regeneration process after spinal hemisection in goldfish.

PMID- 29662436
TI  - The Neuroglial Dialog Between Cannabinoids and Hemichannels.
AB  - The formation of gap junctions was initially thought to be the central role of
      connexins, however, recent evidence had brought to light the high relevance of
      unopposed hemichannels as an independent mechanism for the selective release of
      biomolecules during physiological and pathological conditions. In the healthy
      brain, the physiological opening of astrocyte hemichannels modulates basal
      excitatory synaptic transmission. At the other end, the release of potentially
      neurotoxic compounds through astroglial hemichannels and pannexons has been
      insinuated as one of the functional alterations that negatively affect the
      progression of multiple brain diseases. Recent insights in this matter have
      suggested encannabinoids (eCBs) as molecules that could regulate the opening of
      these channels during diverse conditions. In this review, we discuss and
      hypothesize the possible interplay between the eCB system and the
      hemichannel/pannexon-mediated signaling in the inflamed brain and during event of
      synaptic plasticity. Most findings indicate that eCBs seem to counteract the
      activation of major neuroinflammatory pathways that lead to glia-mediated
      production of TNF-alpha and IL-1beta, both well-known triggers of astroglial
      hemichannel opening. In contrast to the latter, in the normal brain, eCBs
      apparently elicit the Ca2+-activation of astrocyte hemichannels, which could have
      significant consequences on eCB-dependent synaptic plasticity.

PMID- 29662440
TI  - Electrophysiological Properties of Melanin-Concentrating Hormone and Orexin
      Neurons in Adolescent Rats.
AB  - Orexin and melanin-concentrating hormone (MCH) neurons have complementary roles
      in various physiological functions including energy balance and the sleep/wake
      cycle. in vitro electrophysiological studies investigating these cells typically
      use post-weaning rodents, corresponding to adolescence. However, it is unclear
      whether these neurons are functionally mature at this period and whether these
      studies can be generalized to adult cells. Therefore, we examined the
      electrophysiological properties of orexin and MCH neurons in brain slices from
      post-weaning rats and found that MCH neurons undergo an age-dependent reduction
      in excitability, but not orexin neurons. Specifically, MCH neurons displayed an
      age-dependent hyperpolarization of the resting membrane potential (RMP),
      depolarizing shift of the threshold, and decrease in excitatory transmission,
      which reach the adult level by 7 weeks of age. In contrast, basic properties of
      orexin neurons were stable from 4 weeks to 14 weeks of age. Furthermore, a robust
      short-term facilitation of excitatory synapses was found in MCH neurons, which
      showed age-dependent changes during the post-weaning period. On the other hand, a
      strong short-term depression was observed in orexin neurons, which was similar
      throughout the same period. These differences in synaptic responses and age
      dependence likely differentially affect the network activity within the lateral
      hypothalamus where these cells co-exist. In summary, our study suggests that
      orexin neurons are electrophysiologically mature before adolescence whereas MCH
      neurons continue to develop until late adolescence. These changes in MCH neurons
      may contribute to growth spurts or consolidation of adult sleep patterns
      associated with adolescence. Furthermore, these results highlight the importance
      of considering the age of animals in studies involving MCH neurons.

PMID- 29662441
TI  - Characterization of Hair Cell-Like Cells Converted From Supporting Cells After
      Notch Inhibition in Cultures of the Organ of Corti From Neonatal Gerbils.
AB  - The senses of hearing and balance depend upon hair cells, the sensory receptors
      of the inner ear. Hair cells transduce mechanical stimuli into electrical
      activity. Loss of hair cells as a result of aging or exposure to noise and
      ototoxic drugs is the major cause of noncongenital hearing and balance deficits.
      In the ear of non-mammals, lost hair cells can spontaneously be replaced by
      production of new hair cells from conversion of supporting cells. Although
      supporting cells in adult mammals have lost that capability, neonatal supporting
      cells are able to convert to hair cells after inhibition of Notch signaling. We
      questioned whether Notch inhibition is sufficient to convert supporting cells to
      functional hair cells using electrophysiology and electron microscopy. We showed
      that pharmacological inhibition of the canonical Notch pathway in the cultured
      organ of Corti prepared from neonatal gerbils induced stereocilia formation in
      supporting cells (defined as hair cell-like cells or HCLCs) and supernumerary
      stereocilia in hair cells. The newly emerged stereocilia bundles of HCLCs were
      functional, i.e., able to respond to mechanical stimulation with
      mechanotransduction (MET) current. Transmission electron microscopy (TEM) showed
      that HCLCs converted from pillar cells maintained the pillar cell shape and that
      subsurface cisternae, normally observed underneath the cytoskeleton in outer hair
      cells (OHCs), was not present in Deiters' cells-derived HCLCs. Voltage-clamp
      recordings showed that whole-cell currents from Deiters' cells-derived HCLCs
      retained the same kinetics and magnitude seen in normal Deiters' cells and that
      nonlinear capacitance (NLC), an electrical hallmark of OHC electromotility, was
      not detected from any HCLCs measured. Taken together, these results suggest that
      while Notch inhibition is sufficient for promoting stereocilia bundle formation,
      it is insufficient to convert neonatal supporting cells to mature hair cells. The
      fact that Notch inhibition led to stereocilia formation in supporting cells and
      supernumerary stereocilia in existing hair cells appears to suggest that Notch
      signaling may regulate stereocilia formation and stability during development.

PMID- 29662442
TI  - Topographic Organization of Cholinergic Innervation From the Basal Forebrain to
      the Visual Cortex in the Rat.
AB  - Acetylcholine is an important neurotransmitter for the regulation of visual
      attention, plasticity, and perceptual learning. It is released in the visual
      cortex predominantly by cholinergic projections from the basal forebrain, where
      stimulation may produce potentiation of visual processes. However, little is
      known about the fine organization of these corticopetal projections, such as
      whether basal forebrain neurons projecting to the primary and secondary visual
      cortical areas (V1 and V2, respectively) are organized retinotopically. The aim
      of this study was to map these basal forebrain-V1/V2 projections. Microinjections
      of the fluorescent retrograde tracer cholera toxin b fragment in different sites
      within V1 and V2 in Long-Evans rats were performed. Retrogradely labeled cell
      bodies in the horizontal and vertical limbs of the diagonal band of Broca (HDB
      and VDB, respectively), nucleus basalis magnocellularis, and substantia
      innominata (SI), were mapped ex vivo with a computer-assisted microscope stage
      controlled by stereological software. Choline acetyltranferase
      immunohistochemistry was used to identify cholinergic cells. Our results showed a
      predominance of cholinergic projections coming from the HDB. These projections
      were not retinotopically organized but projections to V1 arised from neurons
      located in the anterior HDB/SI whereas projections to V2 arised from neurons
      located throughout the whole extent of HDB/SI. The absence of a clear topography
      of these projections suggests that BF activation can stimulate visual cortices
      broadly.

PMID- 29662443
TI  - Emotion Regulation and Complex Brain Networks: Association Between Expressive
      Suppression and Efficiency in the Fronto-Parietal Network and Default-Mode
      Network.
AB  - Emotion regulation (ER) refers to the "implementation of a conscious or non
      conscious goal to start, stop or otherwise modulate the trajectory of an emotion"
      (Etkin et al., 2015). Whereas multiple brain areas have been found to be involved
      in ER, relatively little is known about whether and how ER is associated with the
      global functioning of brain networks. Recent advances in brain connectivity
      research using graph-theory based analysis have shown that the brain can be
      organized into complex networks composed of functionally or structurally
      connected brain areas. Global efficiency is one graphic metric indicating the
      efficiency of information exchange among brain areas and is utilized to measure
      global functioning of brain networks. The present study examined the relationship
      between trait measures of ER (expressive suppression (ES) and cognitive
      reappraisal (CR)) and global efficiency in resting-state functional brain
      networks (the whole brain network and ten predefined networks) using structural
      equation modeling (SEM). The results showed that ES was reliably associated with
      efficiency in the fronto-parietal network and default-mode network. The finding
      advances the understanding of neural substrates of ER, revealing the relationship
      between ES and efficient organization of brain networks.

PMID- 29662444
TI  - Distinctive Correspondence Between Separable Visual Attention Functions and
      Intrinsic Brain Networks.
AB  - Separable visual attention functions are assumed to rely on distinct but
      interacting neural mechanisms. Bundesen's "theory of visual attention" (TVA)
      allows the mathematical estimation of independent parameters that characterize
      individuals' visual attentional capacity (i.e., visual processing speed and
      visual short-term memory storage capacity) and selectivity functions (i.e., top
      down control and spatial laterality). However, it is unclear whether these
      parameters distinctively map onto different brain networks obtained from
      intrinsic functional connectivity, which organizes slowly fluctuating ongoing
      brain activity. In our study, 31 demographically homogeneous healthy young
      participants performed whole- and partial-report tasks and underwent resting
      state functional magnetic resonance imaging (rs-fMRI). Report accuracy was
      modeled using TVA to estimate, individually, the four TVA parameters. Networks
      encompassing cortical areas relevant for visual attention were derived from
      independent component analysis of rs-fMRI data: visual, executive control, right
      and left frontoparietal, and ventral and dorsal attention networks. Two TVA
      parameters were mapped on particular functional networks. First, participants
      with higher (vs. lower) visual processing speed showed lower functional
      connectivity within the ventral attention network. Second, participants with more
      (vs. less) efficient top-down control showed higher functional connectivity
      within the dorsal attention network and lower functional connectivity within the
      visual network. Additionally, higher performance was associated with higher
      functional connectivity between networks: specifically, between the ventral
      attention and right frontoparietal networks for visual processing speed, and
      between the visual and executive control networks for top-down control. The
      higher inter-network functional connectivity was related to lower intra-network
      connectivity. These results demonstrate that separable visual attention
      parameters that are assumed to constitute relatively stable traits correspond
      distinctly to the functional connectivity both within and between particular
      functional networks. This implies that individual differences in basic attention
      functions are represented by differences in the coherence of slowly fluctuating
      brain activity.

PMID- 29662445
TI  - Dysregulation of Pain- and Emotion-Related Networks in Trigeminal Neuralgia.
AB  - Classical trigeminal neuralgia (TN) is a severe neuropathic facial pain disorder
      associated with increased risks of anxiety and depression. Converging evidence
      suggests that chronic pain pathophysiology involves dysfunctional pain-related
      and emotion-related networks. However, whether these systems are also among the
      culprit networks for TN remains unclear. Here, we aimed to assess TN-related
      anatomical and functional brain anomalies in pain-related and emotion-related
      networks. We investigated differences in gray matter (GM) volume and the related
      resting-state functional connectivity (rsFC) between 29 classical TN patients and
      34 matched healthy controls. Relationships between brain measurement alterations,
      clinical pain and emotional states were identified. A longitudinal observation
      was further conducted to determine whether alterations in the brain could
      renormalize following pain relief. Reduced GM volumes in the bilateral amygdala,
      periaqueductal gray (PAG) and right insula were found in TN patients compared
      with healthy control subjects. Whole-brain rsFC analyses with the four above
      mentioned anatomical regions as seeds identified three significantly altered
      functional circuits, including amygdala-DLPFC, amygdala-mPFC and amygdala
      thalamus/putamen circuitry. The amygdala-DLPFC and amygdala-mPFC circuits were
      associated with clinical pain duration and emotional state ratings, respectively.
      Further longitudinal analysis found that rsFC strength abnormalities in two
      fronto-limbic circuits (left amygdala/left DLPFC and right amygdala/right PFC)
      were resolved after pain relief. Together, structural and functional deficits in
      pain-related and emotion-related networks were associated with TN patients, as
      demonstrated by our multimodal results. Pain relief had protective effects on
      brain functional connectivity within fronto-limbic circuits. Our study provides
      novel insights into the pathophysiology of TN, which may ultimately facilitate
      advances in TN intervention.

PMID- 29662446
TI  - A Knowledge-Based Arrangement of Prototypical Neural Representation Prior to
      Experience Contributes to Selectivity in Upcoming Knowledge Acquisition.
AB  - Knowledge acquisition is a process in which one actively selects a piece of
      information from the environment and assimilates it with prior knowledge.
      However, little is known about the neural mechanism underlying selectivity in
      knowledge acquisition. Here we executed a 2-day human experiment to investigate
      the involvement of characteristic spontaneous activity resembling a so-called
      "preplay" in selectivity in sentence comprehension, an instance of knowledge
      acquisition. On day 1, we presented 10 sentences (prior sentences) that were
      difficult to understand on their own. On the following day, we first measured the
      resting-state functional magnetic resonance imaging (fMRI). Then, we administered
      a sentence comprehension task using 20 new sentences (posterior sentences). The
      posterior sentences were also difficult to understand on their own, but some
      could be associated with prior sentences to facilitate their understanding. Next,
      we measured the posterior sentence-induced fMRI to identify the neural
      representation. From the resting-state fMRI, we extracted the appearances of
      activity patterns similar to the neural representations for posterior sentences.
      Importantly, the resting-state fMRI was measured before giving the posterior
      sentences, and thus such appearances could be considered as preplay-like or
      prototypical neural representations. We compared the intensities of such
      appearances with the understanding of posterior sentences. This gave a positive
      correlation between these two variables, but only if posterior sentences were
      associated with prior sentences. Additional analysis showed the contribution of
      the entorhinal cortex, rather than the hippocampus, to the correlation. The
      present study suggests that prior knowledge-based arrangement of neural activity
      before an experience contributes to the active selection of information to be
      learned. Such arrangement prior to an experience resembles preplay activity
      observed in the rodent brain. In terms of knowledge acquisition, the present
      study leads to a new view of the brain (or more precisely of the brain's
      knowledge) as an autopoietic system in which the brain (or knowledge) selects
      what it should learn by itself, arranges preplay-like activity as a position for
      the new information in advance, and actively reorganizes itself.

PMID- 29662447
TI  - Neural Mechanisms Underlying Time Perception and Reward Anticipation.
AB  - Findings suggest that the physiological mechanisms involved in the reward
      anticipation and time perception partially overlap. But the systematic
      investigation of a potential interaction between time and reward systems using
      neuroimaging is lacking. Eighteen healthy volunteers (all right-handed)
      participated in an event-related functional magnetic resonance imaging (fMRI)
      experiment that employs a visual paradigm that consists monetary reward to assess
      whether the functional neural representations of time perception and reward
      prospection are shared or distinct. Subjects performed a time perception task in
      which observers had to extrapolate the velocity of an occluded moving object in
      "reward" vs. "no-reward" sessions during fMRI scanning. There were also "control
      condition" trials in which participants judged about the color tone change of the
      stimuli. Time perception showed a fronto-parietal (more extensive in the right)
      cingulate and peristriate cortical as well as cerebellar activity. On the other
      hand, reward anticipation activated anterior insular cortex, nucleus accumbens,
      caudate nucleus, thalamus, cerebellum, postcentral gyrus, and peristriate cortex.
      Interaction between the time perception and the reward prospect showed
      dorsolateral, orbitofrontal, medial prefrontal and caudate nucleus activity. Our
      findings suggest that a prefrontal-striatal circuit might integrate reward and
      timing systems of the brain.

PMID- 29662448
TI  - Berry Phenolic Antioxidants - Implications for Human Health?
AB  - Antioxidants present in the diet may have a significant effect on the prophylaxis
      and progression of various diseases associated with oxidative stress. Berries
      contain a range of chemical compounds with antioxidant properties, including
      phenolic compounds. The aim of this review article is to provide an overview of
      the current knowledge of such phenolic antioxidants, and to discuss whether these
      compounds may always be natural gifts for human health, based on both in vitro
      and in vivo studies. It describes the antioxidant properties of fresh berries
      (including aronia berries, grapes, blueberries, sea buckthorn berries,
      strawberries and other berries) and their various products, especially juices and
      wines. Some papers report that these phenolic compounds may sometimes behave like
      prooxidants, and sometimes demonstrate both antioxidant and prooxidant activity,
      while others note they do not behave the same way in vitro and in vivo. However,
      no unwanted or toxic effects (i.e., chemical, hematological or urinary effect)
      have been associated with the consumption of berries or berry juices or other
      extracts, especially aronia berries and aronia products in vivo, and in vitro,
      which may suggest that the phenolic antioxidants found in berries are natural
      gifts for human health. However, the phenolic compound content of berries and
      berry products is not always well described, and further studies are required to
      determine the therapeutic doses of different berry products for use in future
      clinical studies. Moreover, further experiments are needed to understand the
      beneficial effects reported so far from the mechanistic point of view. Therefore,
      greater attention should be paid to the development of well-controlled and high
      quality clinical studies in this area.

PMID- 29662450
TI  - Poly(Ethylene Glycol)-Polylactide Micelles for Cancer Therapy.
AB  - For the treatment of malignancy, many therapeutic agents, including small
      molecules, photosensitizers, immunomodulators, proteins and genes, and so forth,
      have been loaded into nanocarriers for controllable cancer therapy. Among these
      nanocarriers, polymeric micelles have been considered as one of the most
      promising nanocarriers, some of which have already been applied in different
      stages of clinical trials. The successful advantages of polymeric micelles from
      bench to bedside are due to their special core/shell structures, which can carry
      specific drugs in certain disease conditions. Particularly, poly(ethylene glycol)
      polylactide (PEG-PLA) micelles have been considered as one of the most promising
      platforms for drug delivery. The PEG shell effectively prevents the adsorption of
      proteins and phagocytes, thereby evidently extending the blood circulation
      period. Meanwhile, the hydrophobic PLA core can effectively encapsulate many
      therapeutic agents. This review summarizes recent advances in PEG-PLA micelles
      for the treatment of malignancy. In addition, future perspectives for the
      development of PEG-PLA micelles as drug delivery systems are also presented.

PMID- 29662451
TI  - Risk Assessment and Risk Minimization in Nanomedicine: A Need for Predictive,
      Alternative, and 3Rs Strategies.
AB  - The use of nanomaterials in medicine has grown very rapidly, leading to a concern
      about possible health risks. Surely, the application of nanotechnology in
      medicine has many significant potentialities as it can improve human health in at
      least three different ways: by contributing to early disease diagnosis, improved
      treatment outcomes and containment of health care costs. However, toxicology or
      safety assessment is an integral part of any new medical technology and the
      nanotechnologies are no exception. The principle aim of nanosafety studies in
      this frame is to enable safer design of nanomedicines. The most urgent need is
      finding and validating novel approaches able to extrapolate acute in vitro
      results for the prediction of chronic in vivo effects and to this purpose a few
      European initiatives have been launched. While a "safe-by-design" process may be
      considered as utopic, "safer-by-design" is probably a reachable goal in the field
      of nanomedicine.

PMID- 29662449
TI  - Multiple Transceptors for Macro- and Micro-Nutrients Control Diverse Cellular
      Properties Through the PKA Pathway in Yeast: A Paradigm for the Rapidly Expanding
      World of Eukaryotic Nutrient Transceptors Up to Those in Human Cells.
AB  - The nutrient composition of the medium has dramatic effects on many cellular
      properties in the yeast Saccharomyces cerevisiae. In addition to the well-known
      specific responses to starvation for an essential nutrient, like nitrogen or
      phosphate, the presence of fermentable sugar or a respirative carbon source leads
      to predominance of fermentation or respiration, respectively. Fermenting and
      respiring cells also show strong differences in other properties, like storage
      carbohydrate levels, general stress tolerance and cellular growth rate. However,
      the main glucose repression pathway, which controls the switch between
      respiration and fermentation, is not involved in control of these properties.
      They are controlled by the protein kinase A (PKA) pathway. Addition of glucose to
      respiring yeast cells triggers cAMP synthesis, activation of PKA and rapid
      modification of its targets, like storage carbohydrate levels, general stress
      tolerance and growth rate. However, starvation of fermenting cells in a glucose
      medium for any essential macro- or micro-nutrient counteracts this effect,
      leading to downregulation of PKA and its targets concomitant with growth arrest
      and entrance into G0. Re-addition of the lacking nutrient triggers rapid
      activation of the PKA pathway, without involvement of cAMP as second messenger.
      Investigation of the sensing mechanism has revealed that the specific high
      affinity nutrient transporter(s) induced during starvation function as
      transporter-receptors or transceptors for rapid activation of PKA upon re
      addition of the missing substrate. In this way, transceptors have been identified
      for amino acids, ammonium, phosphate, sulfate, iron, and zinc. We propose a
      hypothesis for regulation of PKA activity by nutrient transceptors to serve as a
      conceptual framework for future experimentation. Many properties of transceptors
      appear to be similar to those of classical receptors and nutrient transceptors
      may constitute intermediate forms in the development of receptors from nutrient
      transporters during evolution. The nutrient-sensing transceptor system in yeast
      for activation of the PKA pathway has served as a paradigm for similar studies on
      candidate nutrient transceptors in other eukaryotes and we succinctly discuss the
      many examples of transceptors that have already been documented in other yeast
      species, filamentous fungi, plants, and animals, including the examples in human
      cells.

PMID- 29662452
TI  - A Novel EphA2 Inhibitor Exerts Beneficial Effects in PI-IBS in Vivo and in Vitro
      Models via Nrf2 and NF-kappaB Signaling Pathways.
AB  - Though the detailed pathological mechanism of post-infectious irritable bowel
      syndrome (PI-IBS) remains unclear, accumulating evidence indicates that oxidative
      stress and inflammation are implicated in the process of PI-IBS. Oxidative stress
      and inflammation are regulated by Nrf2 and NF-kappaB signaling pathways,
      respectively. EphA2, a member of Eph receptor family, promotes oxidative stress
      and inflammatory responses via regulation of Nrf2 and NF-kappaB signaling
      pathways in various types of human diseases. Understanding the mechanisms by
      which EphA2 regulate oxidative stress and inflammation in PI-IBS is important for
      the development of new strategies to treat PI-IBS. However, the effects of ALW-II
      41-27, a novel EphA2 inhibitor on PI-IBS and the underlying molecular mechanisms
      have never been studied. In the present study, we showed that ALW-II-41-27
      decreased gastrointestinal motility and abdominal withdrawal reflex (AWR) scores,
      markedly reduced the levels of oxidative stress markers [4-hydroxy-2-nonenal (4
      HNE), protein carbonyl, and 8-hydroxy-2-de-axyguanine (8-OHdG)] and
      proinflammatory cytokines (TNF-alpha, IL-6, IL-17, and ICAM-1), and remarkably
      increased the level of anti-inflammatory cytokine (IL-10) in serum and colon of
      Trichinella spiralis-infected mice. Moreover, ALW-II-41-27 was effective in
      suppressing oxidative stress and inflammation in LPS-treated NCM460 colonic
      cells. Treatment of ALW-II-41-27 reversed the activation of NF-kappaB and
      inactivation of Nrf2 in LPS-treated NCM460 cells. Importantly, these protective
      effects of ALW-II-41-27 were partially inhibited by EphA2 KO and abolished by
      EphA2 overexpression. In conclusion, EphA2 may represent a promising therapeutic
      target for patients with PI-IBS and ALW-II-41-27 might function as a novel
      therapeutic agent for PI-IBS.

PMID- 29662453
TI  - Response of Cultured Neuronal Network Activity After High-Intensity Power
      Frequency Magnetic Field Exposure.
AB  - High-intensity and low frequency (1-100 kHz) time-varying electromagnetic fields
      stimulate the human body through excitation of the nervous system. In power
      frequency range (50/60 Hz), a frequency-dependent threshold of the external
      electric field-induced neuronal modulation in cultured neuronal networks was used
      as one of the biological indicator in international guidelines; however, the
      threshold of the magnetic field-induced neuronal modulation has not been
      elucidated. In this study, we exposed rat brain-derived neuronal networks to a
      high-intensity power frequency magnetic field (hPF-MF), and evaluated the
      modulation of synchronized bursting activity using a multi-electrode array (MEA)
      based extracellular recording technique. As a result of short-term hPF-MF
      exposure (50-400 mT root-mean-square (rms), 50 Hz, sinusoidal wave, 6 s), the
      synchronized bursting activity was increased in the 400 mT-exposed group. On the
      other hand, no change was observed in the 50-200 mT-exposed groups. In order to
      clarify the mechanisms of the 400 mT hPF-MF exposure-induced neuronal response,
      we evaluated it after blocking inhibitory synapses using bicuculline methiodide
      (BMI); subsequently, increase in bursting activity was observed with BMI
      application, and the response of 400 mT hPF-MF exposure disappeared. Therefore,
      it was suggested that the response of hPF-MF exposure was involved in the
      inhibitory input. Next, we screened the inhibitory pacemaker-like neuronal
      activity which showed autonomous 4-10 Hz firing with CNQX and D-AP5 application,
      and it was confirmed that the activity was reduced after 400 mT hPF-MF exposure.
      Comparison of these experimental results with estimated values of the induced
      electric field (E-field) in the culture medium revealed that the change in
      synchronized bursting activity occurred over 0.3 V/m, which was equivalent to the
      findings of a previous study that used the external electric fields. In addition,
      the results suggested that the potentiation of neuronal activity after 400 mT hPF
      MF exposure was related to the depression of autonomous activity of pacemaker
      like neurons. Our results indicated that the synchronized bursting activity was
      increased by hPF-MF exposure (E-field: >0.3 V/m), and the response was due to
      reduced inhibitory pacemaker-like neuronal activity.

PMID- 29662454
TI  - The Biological Clock: A Pivotal Hub in Non-alcoholic Fatty Liver Disease
      Pathogenesis.
AB  - Non-alcoholic fatty liver disease (NAFLD) is the most frequent hepatic pathology
      in the Western world and may evolve into steatohepatitis (NASH), increasing the
      risk of cirrhosis, portal hypertension and hepatocellular carcinoma. NAFLD
      derives from the accumulation of hepatic fat due to discrepant free fatty acid
      metabolism. Other factors contributing to this are deranged nutrients and bile
      acids fluxes as well as alterations in nuclear receptors, hormones, and
      intermediary metabolites, which impact on signaling pathways involved in
      metabolism and inflammation. Autophagy and host gut-microbiota interplay are also
      relevant to NAFLD pathogenesis. Notably, liver metabolic pathways and bile acid
      synthesis as well as autophagic and immune/inflammatory processes all show
      circadian patterns driven by the biological clock. Gut microbiota impacts on the
      biological clock, at the same time as the appropriate timing of metabolic fluxes,
      hormone secretion, bile acid turnover, autophagy and inflammation with
      behavioural cycles of fasting/feeding and sleeping/waking is required to
      circumvent hepatosteatosis, indicating significant interactions of the gut and
      circadian processes in NAFLD pathophysiology. Several time-related factors and
      processes interplay in NAFLD development, with the biological clock proposed to
      act as a network level hub. Deranged physiological rhythms (chronodisruption) may
      also play a role in liver steatosis pathogenesis. The current article reviews how
      the circadian clock circuitry intimately interacts with several mechanisms
      involved in the onset of hepatosteatosis and its progression to NASH, thereby
      contributing to the global NAFLD epidemic.

PMID- 29662455
TI  - Fitness Level and Not Aging per se, Determines the Oxygen Uptake Kinetics
      Response.
AB  - Although aging has been associated to slower [Formula: see text]O2 kinetics, some
      evidence indicates that fitness status and not aging per se might modulate this
      response. The main goal of this study was to examine the [Formula: see text]O2,
      deoxygenated hemoglobin+myoglobin (deoxy-[Hb+Mb]) kinetics, and the NIRS-derived
      vascular reperfusion responses in older compared to young men of different
      training levels (i.e., inactive, recreationally active, and endurance trained).
      Ten young inactive [YI; 26 +/- 5 yrs.; peak [Formula: see text]O2 ([Formula: see
      text]O2peak), 2.96 +/- 0.55 L.min-1], 10 young recreationally active (YR; 26 +/-
      6 yrs.; 3.92 +/- 0.33 L.min-1), 10 young endurance trained (YT; 30 +/- 4 yrs.;
      4.42 +/- 0.32 L.min-1), 7 older inactive (OI; 69 +/- 4 yrs.; 2.50 +/- 0.31 L.min
      1), 10 older recreationally active (OR; 69 +/- 5 yrs.; 2.71 +/- 0.42 L.min-1),
      and 10 older endurance trained (OT; 66 +/- 3 yrs.; 3.20 +/- 0.35 L.min-1) men
      completed transitions of moderate intensity cycling exercise (MODS) to determine
      [Formula: see text]O2 and deoxy-[Hb+Mb] kinetics, and the deoxy-[Hb+Mb]/[Formula:
      see text]O2 ratio. The time constant of [Formula: see text]O2 (tau[Formula: see
      text]O2) was greater in YI (38.8 +/- 10.4 s) and OI (44.1 +/- 10.8 s) compared
      with YR (26.8 +/- 7.5 s) and OR (26.6 +/- 6.5 s), as well as compared to YT (14.8
      +/- 3.4 s), and OT (17.7 +/- 2.7 s) (p < 0.05). tau[Formula: see text]O2 was
      greater in YR and OR compared with YT and OT (p < 0.05). The deoxy
      [Hb+Mb]/[Formula: see text]O2 ratio was greater in YI (1.23 +/- 0.05) and OI
      (1.29 +/- 0.08) compared with YR (1.11 +/- 0.03) and OR (1.13 +/- 0.06), as well
      as compared to YT (1.01 +/- 0.03), and OT (1.06 +/- 0.03) (p < 0.05). Similarly,
      the deoxy-[Hb+Mb]/ [Formula: see text]O2 ratio was greater in YR and OR compared
      with YT and OT (p < 0.05). There was a main effect of training (p = 0.033),
      whereby inactive (p = 0.018) and recreationally active men (p = 0.031) had
      significantly poorer vascular reperfusion than endurance trained men regardless
      of age. This study demonstrated not only that age-related slowing of [Formula:
      see text]O2 kinetics can be eliminated in endurance trained individuals, but also
      that inactive lifestyle negatively impacts the [Formula: see text]O2 kinetics
      response of young healthy individuals.

PMID- 29662456
TI  - Dynamic Regulation of Circulating microRNAs During Acute Exercise and Long-Term
      Exercise Training in Basketball Athletes.
AB  - Emerging evidence indicates the beneficial effects of physical exercise on human
      health, which depends on the intensity, training time, exercise type,
      environmental factors, and the personal health status. Conventional biomarkers
      provide limited insight into the exercise-induced adaptive processes. Circulating
      microRNAs (miRNAs, miRs) are dynamically regulated in response to acute
      exhaustive exercise and sustained rowing, running and cycling exercises. However,
      circulating miRNAs in response to long-term basketball exercise remains unknown.
      Here, we enrolled 10 basketball athletes who will attend a basketball season for
      3 months. Specifically, circulating miRNAs which were involved in angiogenesis,
      inflammation and enriched in muscle and/or cardiac tissues were analyzed at
      baseline, immediately following acute exhaustive exercise and after 3-month
      basketball matches in competitive male basketball athletes. Circulating miR-208b
      was decreased and miR-221 was increased after 3-month basketball exercise, while
      circulating miR-221, miR-21, miR-146a, and miR-210 were reduced at post-acute
      exercise. The change of miR-146a (baseline vs. post-acute exercise) showed linear
      correlations with baseline levels of cardiac marker CKMB and the changes of
      inflammation marker Hs-CRP (baseline vs. post-acute exercise). Besides, linear
      correlation was observed between miR-208b changes (baseline vs. after long-term
      exercise) and AT VO2 (baseline). The changes of miR-221 (baseline vs. after long
      term exercise) were significantly correlated with AT VO2, peak work load and CK
      (after 3-month basketball matches). Although further studies are needed, present
      findings set the stage for defining circulating miRNAs as biomarkers and
      suggesting their physiological roles in long-term exercise training induced
      cardiovascular adaptation.

PMID- 29662457
TI  - A Blind Spot in Research on Foreign Language Effects in Judgment and Decision
      Making.
AB  - One of the most fascinating topics of current investigation in the literature on
      judgment and decision-making concerns the exploration of foreign language effects
      (henceforth, FLE). Specifically, recent research suggests that presenting
      information in a foreign language helps reasoners make better choices. However,
      this piece aims at making scholars aware of a blind spot in this stream of
      research. In particular, research on FLE has imported only one view of judgment
      and decision-making, in which the heuristics that people use are seen as
      conducive to biases and, in turn, to costly mistakes. But heuristics are not
      necessarily a liability, and this article indicates two routes to push forward
      research on FLE in judgment and decision-making. First, research on FLE should be
      expanded to explore also classes of fast and frugal heuristics, which have been
      shown to lead to accurate predictions in several contexts characterized by
      uncertainty. Second, research on FLE should be open to challenge the
      interpretations given to previous FLE findings, since alternative accounts are
      plausible and not ruled out by evidence.

PMID- 29662459
TI  - Too Depleted to Turn In: The Relevance of End-of-the-Day Resource Depletion for
      Reducing Bedtime Procrastination.
AB  - Bedtime procrastination is an important predictor of sleep insufficiency in the
      general population (Kroese et al., 2014b), but little is known about the
      determinants of this self-undermining behavior. As the phenomenon has been
      conceptualized in the literature as a form of self-regulation failure (Kroese et
      al., 2014a), we hypothesized that people's self-regulatory resources in the
      evening would be predictive of going to bed later than they intended.
      Specifically, we examined whether the cumulative effect of resisting desires, a
      measure of self-regulatory resource depletion (Hofmann et al., 2012b), relates to
      bedtime procrastination. Participants (N = 218) reported how many desires they
      had tried to resist during the previous day and the extent of their bedtime
      procrastination. Results show that people who attempted to resist more desires
      were more likely to engage in bedtime procrastination, suggesting that people may
      be less likely to stick to their intended bedtime after a particularly taxing
      day. Implications for intervention strategies are discussed.

PMID- 29662460
TI  - Sensation Seeking and Adaptation in Parabonauts.
AB  - Evidence from extreme environments suggests that there are relationships between
      difficulties of adaptation and psychological factors such as personality. In the
      framework of microgravity research on humans, the aim of this exploratory study
      was to investigate inter-individual differences of parabonauts on the basis of
      quality of adaptation to the physical demands of parabolic flights. The
      personality characteristics of two groups of parabonauts with a different quality
      of adaptation (an Adaptive group, N = 7, and a Maladaptive group, N = 15) were
      assessed using the Sensation Seeking Scale, Brief COPE, and MSSQ-Short. Compared
      to the Maladaptive group, the individuals of the Adaptive group scored higher on
      Boredom Susceptibility (i.e., a subscale of the Sensation Seeking Scale), lower
      on scales of susceptibility to motion sickness (MSSQ-Short) and tended to score
      lower on Instrumental Support Seeking (i.e., a subscale of the Brief COPE). These
      results suggest that individuals of the Adaptive group are more intolerant to
      monotony, present an aversion to repetitive and routine activities, are less
      susceptible to motion sickness and less dependent on problem-focused strategies.
      These characteristics may have contributed to developing a certain degree of
      flexibility in these subjects when faced with the parabolic flight situation and
      thus, may have favored them. The identification of differences of personality
      characteristics between individuals who have expressed difficulties of adaptation
      from those who have adapted successfully could help to prevent the risk of
      maladaptation and improve the well-being of (future) commercial or occupational
      aerospace passengers. More generally, these results could be extended to extreme
      environments and professional and/or sports domains likely to involve risk taking
      and unusual situations.

PMID- 29662458
TI  - Inhibition, Updating Working Memory, and Shifting Predict Reading Disability
      Symptoms in a Hybrid Model: Project KIDS.
AB  - Recent achievement research suggests that executive function (EF), a set of
      regulatory processes that control both thought and action necessary for goal
      directed behavior, is related to typical and atypical reading performance. This
      project examines the relation of EF, as measured by its components, Inhibition,
      Updating Working Memory, and Shifting, with a hybrid model of reading disability
      (RD). Our sample included 420 children who participated in a broader intervention
      project when they were in KG-third grade (age M = 6.63 years, SD = 1.04 years,
      range = 4.79-10.40 years). At the time their EF was assessed, using a parent
      report Behavior Rating Inventory of Executive Function (BRIEF), they had a mean
      age of 13.21 years (SD = 1.54 years; range = 10.47-16.63 years). The hybrid model
      of RD was operationalized as a composite consisting of four symptoms, and set so
      that any child could have any one, any two, any three, any four, or none of the
      symptoms included in the hybrid model. The four symptoms include low word reading
      achievement, unexpected low word reading achievement, poorer reading
      comprehension compared to listening comprehension, and dual-discrepancy response
      to-intervention, requiring both low achievement and low growth in word reading.
      The results of our multilevel ordinal logistic regression analyses showed a
      significant relation between all three components of EF (Inhibition, Updating
      Working Memory, and Shifting) and the hybrid model of RD, and that the strength
      of EF's predictive power for RD classification was the highest when RD was
      modeled as having at least one or more symptoms. Importantly, the chances of
      being classified as having RD increased as EF performance worsened and decreased
      as EF performance improved. The question of whether any one EF component would
      emerge as a superior predictor was also examined and results showed that
      Inhibition, Updating Working Memory, and Shifting were equally valuable as
      predictors of the hybrid model of RD. In total, all EF components were
      significant and equally effective predictors of RD when RD was operationalized
      using the hybrid model.

PMID- 29662461
TI  - Gender Gaps in Letter-Sound Knowledge Persist Across the First School Year.
AB  - Literacy is the cornerstone of a primary school education and enables the
      intellectual and social development of young children. Letter-sound knowledge has
      been identified as critical for developing proficiency in reading. This study
      explored the development of letter-sound knowledge in relation to gender during
      the first year of primary school. 485 Norwegian children aged 5-6 years completed
      assessment of letter-sound knowledge, i.e., uppercase letters- name; uppercase
      letter -sound; lowercase letters- name; lowercase letter-sound. The children were
      tested in the beginning, middle, and end of their first school year. The results
      revealed a clear gender difference in all four variables in favor of the girls
      which were relatively constant over time. Implications for understanding the role
      of gender and letter-sound knowledge for later reading performance are discussed.

PMID- 29662462
TI  - Visual Grouping in Accordance With Utterance Planning Facilitates Speech
      Production.
AB  - Research on language production has focused on the process of utterance planning
      and involved studying the synchronization between visual gaze and the production
      of sentences that refer to objects in the immediate visual environment. However,
      it remains unclear how the visual grouping of these objects might influence this
      process. To shed light on this issue, the present research examined the effects
      of the visual grouping of objects in a visual display on utterance planning in
      two experiments. Participants produced utterances of the form "The snail and the
      necklace are above/below/on the left/right side of the toothbrush" for objects
      containing these referents (e.g., a snail, a necklace and a toothbrush). These
      objects were grouped using classic Gestalt principles of color similarity
      (Experiment 1) and common region (Experiment 2) so that the induced perceptual
      grouping was congruent or incongruent with the required phrasal organization. The
      results showed that speech onset latencies were shorter in congruent than
      incongruent conditions. The findings therefore reveal that the congruency between
      the visual grouping of referents and the required phrasal organization can
      influence speech production. Such findings suggest that, when language is
      produced in a visual context, speakers make use of both visual and linguistic
      cues to plan utterances.

PMID- 29662463
TI  - How Do You Manage Change in Organizations? Training, Development, Innovation, and
      Their Relationships.
AB  - The article aims to be a reflective paper on the interconnected concepts of
      training, development and innovation and the potential they have in dealing with
      change in organizations. We call change both the process through which something
      becomes different and the result of that process. Change management is the
      expression used to define the complex of activities, functions, and tools (such
      as training courses) through which an organization deals with the introduction of
      something new that is relevant for both its survival and growth. Training and
      development are labels used to define those educational activities implemented in
      organizations to empower the competences of workers, employees and managers in
      the lifelong learning perspective of improving their performance. Consequently,
      we define competences as those personal characteristics that allow people to be
      effective in the changing contexts of both workplace and everyday life. They are
      also necessary in organizational innovation, which is the process of transforming
      ideas or inventions into goods or services that generate value and for which
      customers will pay. Training, development, and innovation are three different but
      interconnected functions by which organizations manage change. What is the state
      of the art of the literature dealing with these topics? Here, is a critical
      review on the matter.

PMID- 29662464
TI  - White Matter Tract Alterations in Drug-Naive Parkinson's Disease Patients With
      Impulse Control Disorders.
AB  - Impulse control disorders (ICDs) are relatively frequent in patients with
      Parkinson's disease (PD), although it is still unclear whether an underlying
      pathological process plays a significant role in the development of ICD in PD
      apart from dopaminergic replacement therapy. In this study, we have investigated
      alterations of white matter tract in drug-naive PD patients with ICDs via
      diffusion MRI connectometry. Our results showed that disrupted connectivity in
      the complex network of dynamic connections between cerebellum, basal ganglia,
      cortex, and its spinal projections serves as the underlying neuropathology of ICD
      in PD not interfered with the contribution of dopaminergic replacement therapy.
      These findings provide the first evidence on involved white matter tracts in the
      neuropathogenesis of ICD in drug-naive PD population, supporting the hypothesis
      that neural disturbances intrinsic to PD may confer an increased risk for ICDs.
      Future studies are needed to validate the attribution of the impaired
      corticocerebellar network to impulsivity in PD.

PMID- 29662465
TI  - The Length of SNCA Rep1 Microsatellite May Influence Cognitive Evolution in
      Parkinson's Disease.
AB  - Background: Alpha-synuclein is a constituent of Lewy bodies and mutations of its
      gene cause familial Parkinson's disease (PD). A previous study showed that a
      variant of the alpha-synuclein gene (SNCA), namely the 263 bp allele of Rep1 was
      associated with faster motor progression in PD. On the contrary, a recent report
      failed to detect a detrimental effect of Rep1 263 on both motor and cognitive
      outcomes in PD. Aim of this study was to evaluate the influence of the Rep1
      variants on disease progression in PD patients. Methods: We recruited and
      genotyped for SNCA Rep1 426 PD patients with age at onset >=40 years and disease
      duration >=4 years. We then analyzed frequency and time of occurrence of wearing
      off, dyskinesia, freezing of gait, visual hallucinations, and dementia using a
      multivariate Cox's proportional hazards regression model. Results: SNCA Rep1 263
      carriers showed significantly increased risk of both dementia (HR = 3.03) and
      visual hallucinations (HR = 2.69) compared to 263 non-carriers. Risk of motor
      complications did not differ in the two groups. Conclusion: SNCA Rep1 263 allele
      is associated with a worse cognitive outcome in PD.

PMID- 29662466
TI  - Kisspeptin and Cancer: Molecular Interaction, Biological Functions, and Future
      Perspectives.
AB  - Cancer disease is the second leading cause of death in the world and one of the
      main fields of medical research. Although there is now a greater understanding of
      biological mechanisms of uncontrolled cell growth, invasiveness and
      metastasization, the multi-step process of cancer development and evolution is
      still incompletely understood. The inhibition of molecules activated in cancer
      metastasization is an hot topic in cancer research. Among the known
      antimetastatic genes, KiSS-1 is involved in the metastatic cascade by preventing
      growth of metastasis. Moreover, loss of KiSS-1 protein expression by tumor cells
      has been associated with a more aggressive phenotype. KiSS-1 gene encodes a 145
      amino acid protein, which following proteolytic cleavage, generates a family of
      kisspeptins (Kp-10, -13, and -14), that are endogenous agonists for the G-protein
      coupled receptor (GPR54). The antitumor effect of KiSS-1 was primarily associated
      with the inhibition of proliferation, migration and cell invasion and,
      consequently, the reduced formation of metastasis and intratumoral microvessels.
      In this review, we highlight the latest data on the role of kisspeptin signaling
      in the suppression of metastasis in various cancer types and the use modulators
      of KiSS/GPR54 signaling as potential novel therapeutic agents for the treatment
      of cancer.

PMID- 29662468
TI  - Ecology, Epidemiology and Disease Management of Ralstonia syzygii in Indonesia.
AB  - Ralstonia solanacearum species complex phylotype IV strains, which have been
      primarily isolated from Indonesia, Australia, Japan, Korea, and Malaysia, have
      undergone recent taxonomic and nomenclatural changes to be placed in the species
      Ralstonia syzygii. This species contains three subspecies; Ralstonia syzygii
      subsp. syzygii, a pathogen causing Sumatra disease of clove trees in Indonesia,
      Ralstonia syzygii subsp. indonesiensis, the causal pathogen of bacterial wilt
      disease on a wide range of host plants, and Ralstonia syzygii subsp.
      celebesensis, the causal pathogen of blood disease on Musa spp. In Indonesia,
      these three subspecies have devastated the cultivation of susceptible host plants
      which have high economic value. Limited knowledge on the ecology and epidemiology
      of the diseases has hindered the development of effective control strategies. In
      this review, we provide insights into the ecology, epidemiology and disease
      control of these three subspecies of Ralstonia syzygii.

PMID- 29662467
TI  - Multilocus Sequence Typing and Virulence-Associated Gene Profile Analysis of
      Staphylococcus aureus Isolates From Retail Ready-to-Eat Food in China.
AB  - The aim of this study was to characterize the subtypes and virulence profiles of
      69 Staphylococcus aureus isolates obtained from retail ready-to-eat food in
      China. The isolates were analyzed using multilocus sequence typing (MLST) and
      polymerase chain reaction (PCR) analysis of important virulence factor genes,
      including the staphylococcal enterotoxin (SE) genes (sea, seb, sec, sed, see,
      seg, seh, sei, sej), the exfoliative toxin genes (eta and etb), the toxic shock
      syndrome toxin-1 gene (tst), and the Panton-Valentine leucocidin-encoding gene
      (pvl). The isolates encompassed 26 different sequence types (STs), including four
      new STs (ST3482, ST3484, ST3485, ST3504), clustered in three clonal complexes and
      17 singletons. The most prevalent STs were ST1, ST6, and ST15, constituting 34.8%
      of all isolates. Most STs (15/26, 57.7%) detected have previously been associated
      with human infections. All 13 toxin genes examined were detected in the S. aureus
      isolates, with 84.1% of isolates containing toxin genes. The three most prevalent
      toxin genes were seb (36.2%), sea (33.3%), and seg (33.3%). The classical SE
      genes (sea-see), which contribute significantly to staphylococcal food poisoning
      (SFP), were detected in 72.5% of the S. aureus isolates. In addition, pvl, eta,
      etb, and tst were found in 11.6, 10.1, 10.1, and 7.2% of the S. aureus isolates,
      respectively. Strains ST6 carrying sea and ST1 harboring sec-seh enterotoxin
      profile, which are the two most common clones associated with SFP, were also
      frequently detected in the food samples in this study. This study indicates that
      these S. aureus isolates present in Chinese ready-to-eat food represents a
      potential public health risk. These data are valuable for epidemiological
      studies, risk management, and public health strategies.

PMID- 29662469
TI  - Halotolerant Exiguobacterium profundum PHM11 Tolerate Salinity by Accumulating L
      Proline and Fine-Tuning Gene Expression Profiles of Related Metabolic Pathways.
AB  - Salinity stress is one of the serious factors, limiting production of major
      agricultural crops; especially, in sodic soils. A number of approaches are being
      applied to mitigate the salt-induced adverse effects in agricultural crops
      through implying different halotolerant microbes. In this aspect, a halotolerant,
      Exiguobacterium profundum PHM11 was evaluated under eight different salinity
      regimes; 100, 250, 500, 1000, 1500, 2000, 2500, and 3000 mM to know its inherent
      salt tolerance limits and salt-induced consequences affecting its natural
      metabolism. Based on the stoichiometric growth kinetics; 100 and 1500 mM
      concentrations were selected as optimal and minimal performance limits for PHM11.
      To know, how salt stress affects the expression profiles of regulatory genes of
      its key metabolic pathways, and total production of important metabolites;
      biomass, carotenoids, beta-carotene production, IAA and proline contents, and
      expression profiles of key genes affecting the protein folding, structural
      adaptations, transportation across the cell membrane, stress tolerance,
      carotenoids, IAA and mannitol production in PHM11 were studied under 100 and 1500
      mM salinity. E. profundum PHM11 showed maximum and minimum growth, biomass and
      metabolite production at 100 and 1500 mM salinity respectively. Salt-induced fine
      tuning of expression profiles of key genes of stress pathways was determined in
      halotolerant bacterium PHM11.

PMID- 29662471
TI  - Maize Endophytic Bacterial Diversity as Affected by Soil Cultivation History.
AB  - The bacterial endophytic communities residing within roots of maize (Zea mays L.)
      plants cultivated by a sustainable management in soils from the Quechua maize
      belt (Peruvian Andes) were examined using tags pyrosequencing spanning the V4 and
      V5 hypervariable regions of the 16S rRNA. Across four replicate libraries, two
      corresponding to sequences of endophytic bacteria from long time maize-cultivated
      soils and the other two obtained from fallow soils, 793 bacterial sequences were
      found that grouped into 188 bacterial operational taxonomic units (OTUs, 97%
      genetic similarity). The numbers of OTUs in the libraries from the maize
      cultivated soils were significantly higher than those found in the libraries from
      fallow soils. A mean of 30 genera were found in the fallow soil libraries and 47
      were in those from the maize-cultivated soils. Both alpha and beta diversity
      indexes showed clear differences between bacterial endophytic populations from
      plants with different soil cultivation history and that the soils cultivated for
      long time requires a higher diversity of endophytes. The number of sequences
      corresponding to main genera Sphingomonas, Herbaspirillum, Bradyrhizobium and
      Methylophilus in the maize-cultivated libraries were statistically more abundant
      than those from the fallow soils. Sequences of genera Dyella and Sreptococcus
      were significantly more abundant in the libraries from the fallow soils. Relative
      abundance of genera Burkholderia, candidatus Glomeribacter, Staphylococcus,
      Variovorax, Bacillus and Chitinophaga were similar among libraries. A canonical
      correspondence analysis of the relative abundance of the main genera showed that
      the four libraries distributed in two clearly separated groups. Our results
      suggest that cultivation history is an important driver of endophytic
      colonization of maize and that after a long time of cultivation of the soil the
      maize plants need to increase the richness of the bacterial endophytes
      communities.

PMID- 29662472
TI  - Direct Growth of Bacteria in Headspace Vials Allows for Screening of Volatiles by
      Gas Chromatography Mass Spectrometry.
AB  - Bacterially produced volatile organic compounds (VOCs) can modify growth patterns
      of eukaryotic hosts and competing/cohabiting microbes. These compounds have been
      implicated in skin disorders and attraction of biting pests. Current methods to
      detect and characterize VOCs from microbial cultures can be laborious and low
      throughput, making it difficult to understand the behavior of microbial
      populations. In this work we present an efficient method employing gas
      chromatography/mass spectrometry with autosampling to characterize VOC profiles
      from solid-phase bacterial cultures. We compare this method to complementary
      plate-based assays and measure the effects of growth media and incubation
      temperature on the VOC profiles from a well-studied Pseudomonas aeruginosa PAO1
      system. We observe that P. aeruginosa produces longer chain VOCs, such as 2
      undecanone and 2-undecanol in higher amounts at 37 degrees C than 30 degrees C.
      We demonstrate the throughput of this method by studying VOC profiles from a
      representative collection of skin bacterial isolates under three parallel growth
      conditions. We observe differential production of various aldehydes and ketones
      depending on bacterial strain. This generalizable method will support screening
      of bacterial populations in a variety of research areas.

PMID- 29662470
TI  - Basis of Virulence in Enterotoxin-Mediated Staphylococcal Food Poisoning.
AB  - The Staphylococcus aureus enterotoxins are a superfamily of secreted virulence
      factors that share structural and functional similarities and possess potent
      superantigenic activity causing disruptions in adaptive immunity. The
      enterotoxins can be separated into two groups; the classical (SEA-SEE) and the
      newer (SEG-SElY and counting) enterotoxin groups. Many members from both these
      groups contribute to the pathogenesis of several serious human diseases,
      including toxic shock syndrome, pneumonia, and sepsis-related infections.
      Additionally, many members demonstrate emetic activity and are frequently
      responsible for food poisoning outbreaks. Due to their robust tolerance to
      denaturing, the enterotoxins retain activity in food contaminated previously with
      S. aureus. The genes encoding the enterotoxins are found mostly on a variety of
      different mobile genetic elements. Therefore, the presence of enterotoxins can
      vary widely among different S. aureus isolates. Additionally, the enterotoxins
      are regulated by multiple, and often overlapping, regulatory pathways, which are
      influenced by environmental factors. In this review, we also will focus on the
      newer enterotoxins (SEG-SElY), which matter for the role of S. aureus as an
      enteropathogen, and summarize our current knowledge on their prevalence in recent
      food poisoning outbreaks. Finally, we will review the current literature
      regarding the key elements that govern the complex regulation of enterotoxins,
      the molecular mechanisms underlying their enterotoxigenic, superantigenic, and
      immunomodulatory functions, and discuss how these activities may collectively
      contribute to the overall manifestation of staphylococcal food poisoning.

PMID- 29662473
TI  - HU of Streptococcus pneumoniae Is Essential for the Preservation of DNA
      Supercoiling.
AB  - The histone-like protein HU is a conserved nucleoid-associated protein that is
      involved in the maintenance of the bacterial chromosome architecture. It is the
      only known nucleoid-associated protein in Streptococcus pneumoniae, but it has
      not been studied. The pneumococcal gene encoding this protein, hlp, is shown
      herein to be essential for cell viability. Its disruption was only possible
      either when it was duplicated in the chromosome and its expression induced from
      the P Zn promoter, or when hlp was cloned into a plasmid under the control of the
      inducible P mal promoter. In vitro assays indicated that pneumococcal HU shows a
      preference for binding to supercoiled DNA rather than to linear or nicked DNA. In
      vivo experiments in which the amount of HU was manipulated showed a relationship
      between the amount of HU and the level of DNA supercoiling. A twofold reduction
      in the amount of HU triggered a 21% increase in DNA relaxation in untreated
      cells. However, in cells treated with novobiocin, a drug that relaxes DNA by
      inhibiting DNA gyrase, a 35% increase in DNA relaxation was observed, instead of
      the expected 20% in cells with a constitutive HU amount. Conversely, a fourfold
      HU increase caused only 14% of DNA relaxation in the presence of novobiocin.
      Taken together, these results support an essential role for HU in the maintenance
      of DNA supercoiling in S. pneumoniae.

PMID- 29662474
TI  - Genotypic and Lipid Analyses of Strains From the Archaeal Genus Halorubrum Reveal
      Insights Into Their Taxonomy, Divergence, and Population Structure.
AB  - To gain a better understanding of how divergence occurs, and how taxonomy can
      benefit from studying natural populations, we isolated and examined 25 closely
      related Halorubrum strains obtained from different hypersaline communities and
      compared them to validly named species and other reference strains using five
      taxonomic study approaches: phylogenetic analysis using the 16S rRNA gene and
      multilocus sequencing analysis (MLSA), polar lipid profiles (PLP), average
      nucleotide identity (ANI) and DNA-DNA hybridization (DDH). 16S rRNA gene sequence
      could not differentiate the newly isolated strains from described species, while
      MLSA grouped strains into three major clusters. Two of those MLSA clusters
      distinguished candidates for new species. The third cluster with concatenated
      sequence identity equal to or greater than 97.5% was comprised of strains from
      Aran-Bidgol Lake (Iran) and solar salterns in Namibia and Spain, and two
      previously described species isolated from Mexico and Algeria. PLP and DDH
      analyses showed that Aran-Bidgol strains formed uniform populations, and that
      strains isolated from other geographic locations were heterogeneous and
      divergent, indicating that they may constitute different species. Therefore,
      applying only sequencing approaches and similarity cutoffs for circumscribing
      species may be too conservative, lumping concealed diversity into a single taxon.
      Further, our data support the interpretation that local populations experience
      unique evolutionary homogenization pressures, and once relieved of insular
      constraints (e.g., through migration) are free to diverge.

PMID- 29662475
TI  - The LuxR Regulators PcoR and RfiA Co-regulate Antimicrobial Peptide and Alginate
      Production in Pseudomonas corrugata.
AB  - Cyclic lipopeptides (CLPs) are considered as some of the most important secondary
      metabolites in different plant-associated bacteria, thanks to their
      antimicrobial, cytotoxic, and surfactant properties. In this study, our aim was
      to investigate the role of the Quorum Sensing (QS) system, PcoI/PcoR, and the
      LuxR-type transcriptional regulator RfiA in CLP production in the phytopatogenic
      bacterium, Pseudomonas corrugata based on our previous work where we reported
      that the pcoR and rfiA mutants were devoid of the CLPs cormycin and corpeptin
      production. Due to the close genetic link between the QS system and the RfiA
      (rfiA is co-transcribed with pcoI), it was difficult to ascertain the specific
      regulatory role in the expression of target genes. A transcriptional approach was
      undertaken to identify the specific role of the PcoR and RfiA transcriptional
      regulators for the expression of genes involved in CLP production. The RNA-seq
      based transcriptional analysis of the wild-type (WT) strain CFBP 5454 in
      comparison with GL2 (pcoR mutant) and GLRFIA (rfiA mutant) was performed in
      cultural conditions favoring CLP production. Differential gene expression
      revealed that 152 and 130 genes have significantly different levels of expression
      in the pcoR and rfiA mutants, respectively. Of these, the genes linked to the
      biosynthesis of CLPs and alginate were positively controlled by both PcoR and
      RfiA. Blast homology analysis showed that 19 genes in a large CLP biosynthetic
      cluster involved in the production of three antimicrobial peptides, which span
      approximately 3.5% of the genome, are strongly over-expressed in the WT strain.
      Thus, PcoR and RfiA function mainly as activators in the production of bioactive
      CLPs, in agreement with phenotype analysis of mutants. RNA-seq also revealed that
      almost all the genes in the structural/biosynthetic cluster of alginate
      exopolysaccharide (EPS) are under the control of the PcoR-RfiA regulon, as
      supported by the 10-fold reduction in total EPS yield isolated in both mutants in
      comparison to the parent strain. A total of 68 and 38 gene expressions was
      independently regulated by PcoR or RfiA proteins, respectively, but at low level.
      qPCR experiments suggest that growth medium and plant environment influence the
      expression of CLP and alginate genes.

PMID- 29662477
TI  - New Genes Involved in Mild Stress Response Identified by Transposon Mutagenesis
      in Lactobacillus paracasei.
AB  - Lactic acid bacteria (LAB) are associated with various plant, animal, and human
      niches and are also present in many fermented foods and beverages. Thus, they are
      subjected to several stress conditions and have developed advanced response
      mechanisms to resist, adapt, and grow. This work aimed to identify the genes
      involved in some stress adaptation mechanisms in LAB. For this purpose, global
      reverse genetics was applied by screening a library of 1287 Lactobacillus
      paracasei transposon mutants for mild monofactorial stresses. This library was
      submitted independently to heat (52 degrees C, 30 min), ethanol (170 g.L-1, 30
      min), salt (NaCl 0.8 M, 24 h), acid (pH 4.5, 24 h), and oxidative (2 mM H2O2, 24
      h) perturbations which trigger mild monofactorial stresses compatible with
      bacterial adaptation. Stress sensitivity of mutants was determined either by
      evaluating viability using propidium iodide (PI) staining, or by following growth
      inhibition through turbidity measurement. The screening for heat and ethanol
      stresses lead respectively to the identification of 63 and 27 genes/putative
      promoters whose disruption lead to an increased sensitivity. Among them, 14 genes
      or putative promoters were common for both stresses. For salt, acid and oxidative
      stresses, respectively 8, 6, and 9 genes or putative promoters were identified as
      essential for adaptation to these unfavorable conditions, with only three genes
      common to at least two stresses. Then, RT-qPCR was performed on selected stress
      response genes identified by mutant screenings in order to evaluate if their
      expression was modified in response to stresses in the parental strain. Eleven
      genes (membrane, transposase, chaperone, nucleotide and carbohydrate metabolism,
      and hypothetical protein genes) were upregulated during stress adaptation for at
      least two stresses. Seven genes, encoding membrane functions, were upregulated in
      response to a specific stress and thus could represent potential transcriptomic
      biomarkers. The results highlights that most of the genes identified by global
      reverse genetics are specifically required in response to one stress and that
      they are not differentially transcribed during stress in the parental strain.
      Most of these genes have not been characterized as stress response genes and
      provide new insights into the adaptation of lactic acid bacteria to their
      environment.

PMID- 29662476
TI  - Improvement of the Uranium Sequestration Ability of a Chlamydomonas sp. (ChlSP
      Strain) Isolated From Extreme Uranium Mine Tailings Through Selection for
      Potential Bioremediation Application.
AB  - The extraction and processing of uranium (U) have polluted large areas worldwide,
      rendering anthropogenic extreme environments inhospitable to most species.
      Noticeably, these sites are of great interest for taxonomical and applied
      bioprospection of extremotolerant species successfully adapted to U tailings
      contamination. As an example, in this work we have studied a microalgae species
      that inhabits extreme U tailings ponds at the Saelices mining site (Salamanca,
      Spain), characterized as acidic (pH between 3 and 4), radioactive (around 4 MUSv
      h-1) and contaminated with metals, mainly U (from 25 to 48 mg L-1) and zinc (from
      17 to 87 mg L-1). After isolation of the extremotolerant ChlSP strain,
      morphological characterization and internal transcribed spacer (ITS)-5.8S gene
      sequences placed it in the Chlamydomonadaceae, but BLAST analyses identity
      values, against the nucleotide datasets at the NCBI database, were very low
      (<92%). We subjected the ChlSP strain to an artificial selection protocol to
      increase the U uptake and investigated its response to selection. The ancestral
      strain ChlSP showed a U-uptake capacity of ~4.30 mg U g-1 of dry biomass (DB).
      However, the artificially selected strain ChlSG was able to take up a total of
      ~6.34 mg U g-1 DB, close to the theoretical maximum response (~7.9 mg U g-1 DB).
      The selected ChlSG strain showed two possible U-uptake mechanisms: the greatest
      proportion by biosorption onto cell walls (ca. 90%), and only a very small
      quantity, ~0.46 mg g-1 DB, irreversibly bound by bioaccumulation. Additionally,
      the kinetics of the U-uptake process were characterized during a microalgae
      growth curve; ChlSG cells removed close to 4 mg L-1 of U in 24 days. These
      findings open up promising prospects for sustainable management of U tailings
      waters based on newly evolved extremotolerants and outline the potential of
      artificial selection in the improvement of desired features in microalgae by
      experimental adaptation and selection.

PMID- 29662478
TI  - BALB/c and C57BL/6 Mice Cytokine Responses to Trypanosoma cruzi Infection Are
      Independent of Parasite Strain Infectivity.
AB  - Trypanosoma cruzi is the etiologic agent of Chagas' disease, which affects 6-7
      million people worldwide. Different strains of T. cruzi present specific
      genotypic and phenotypic characteristics that affect the host-pathogen
      interactions, and thus, the parasite has been classified into six groups (TcI to
      TcVI). T. cruzi infection presents two clinical phases, acute and chronic, both
      with distinct characteristics and important participation by the immune system.
      However, the specific contributions of parasite and host factors in the disease
      phases are not yet fully understood. The murine model for Chagas' disease is well
      established and reproduces important features of the human infection, providing
      an experimental basis for the study of host lineages and parasite strains. Thus,
      we evaluated acute and chronic infection by the G (TcI) and CL (TcVI) strains of
      T. cruzi, which have distinct tropisms and infectivity, in two inbred mice
      lineages (C57BL/6 and BALB/c) that display variable degrees of susceptibility to
      different T. cruzi strains. Analysis of the parasite loads in host tissues by
      qPCR showed that CL strain established an infection faster than the G strain; at
      the same time, the response in BALB/c mice, although diverse in terms of cytokine
      secretion, was initiated earlier than that in C57BL/6 mice. At the parasitemia
      peak in the acute phase, we observed, either by confocal microscopy or by qPCR,
      that the infection was disseminated in all groups analyzed, with some differences
      concerning parasite tropism; at this point, all animals responded to infection by
      increasing the serum concentrations of cytokines. However, BALB/c mice seemed to
      better regulate the immune response than C57BL/6 mice. Indeed, in the chronic
      phase, C57BL/6 mice still presented exacerbated cytokine and chemokine responses.
      In summary, our results indicate that in these experimental models, the
      deregulation of immune response that is typical of chronic Chagas' disease may be
      due to control loss over pro- and anti-inflammatory cytokines early in the acute
      phase of the disease, depending primarily on the host background rather than the
      parasite strain.

PMID- 29662479
TI  - Comparison of Two Molecular Assays for Detection and Characterization of
      Aspergillus fumigatus Triazole Resistance and Cyp51A Mutations in Clinical
      Isolates and Primary Clinical Samples of Immunocompromised Patients.
AB  - In hematological patients, the incidence of invasive aspergillosis (IA) caused by
      azole resistant Aspergillus fumigatus (ARAf) is rising. As the diagnosis of IA is
      rarely based on positive culture in this group of patients, molecular detection
      of resistance mutations directly from clinical samples is crucial. In addition to
      the in-house azole resistance ARAf polymerase chain reaction (PCR) assays
      detecting the frequent mutation combinations TR34/L98H, TR46/Y121F/T289A, and
      M220 in the Aspergillus fumigatus (A. fumigatus) Cyp51A gene by subsequent DNA
      sequence analysis, we investigated in parallel the commercially available
      AsperGenius(r) real time PCR system in detecting the Cyp51A alterations TR34/L98H
      and Y121F/T289A directly from 52 clinical samples (15 biopsies, 22
      bronchoalveolar lavage (BAL), 15 cerebrospinal fluid (CSF) samples) and ARAf
      isolates (n = 3) of immunocompromised patients. We analyzed DNA aliquots and
      compared both methods concerning amplification and detection of Aspergillus DNA
      and Cyp51A alterations. As positive control for the feasibility of our novel
      Y121F and T289A PCR assays, we used two A. fumigatus isolates with the
      TR46/Y121F/T289A mutation combination isolated from hematological patients with
      known Cyp51A alterations and a lung biopsy sample of a patient with acute myeloid
      leukemia (AML). The rate of positive ARAf PCR results plus successful sequencing
      using the ARAf PCR assays was 61% in biopsies, 29% in CSF, 67% in BAL samples and
      100% in isolates. In comparison the amount of positive PCRs using the
      AsperGenius(r) assays was 47% in biopsies, 42% in CSF, 59% in BAL samples and
      100% in isolates. Altogether 17 Cyp51A alterations were detected using our ARAf
      PCRs plus DNA sequencing and therefrom 10 alterations also by the AsperGenius(r)
      system. The comparative evaluation of our data revealed that our conventional PCR
      assays are more sensitive in detecting ARAf in BAL and biopsy samples, whereby
      differences were not significant. The advantage of the AsperGenius(r) system is
      the time saving aspect. We consider non-culture based molecular detection of
      Aspergillus triazole resistance to be of high epidemiological and clinical
      relevance in patients with hematological malignancies.

PMID- 29662480
TI  - Comparative Analysis of the Microbiota Between Sheep Rumen and Rabbit Cecum
      Provides New Insight Into Their Differential Methane Production.
AB  - The rumen and the hindgut represent two different fermentation organs in
      herbivorous mammals, with the former producing much more methane than the latter.
      The objective of this study was to elucidate the microbial underpinning of such
      differential methane outputs between these two digestive organs. Methane
      production was measured from 5 adult sheep and 15 adult rabbits, both of which
      were placed in open-circuit respiratory chambers and fed the same diet (alfalfa
      hay). The sheep produced more methane than the rabbits per unit of metabolic body
      weight, digestible neutral detergent fiber, and acid detergent fiber. pH in the
      sheep rumen was more than 1 unit higher than that in the rabbit cecum. The
      acetate to propionate ratio in the rabbit cecum was more than threefold greater
      than that in the sheep rumen. Comparative analysis of 16S rRNA gene amplicon
      libraries revealed distinct microbiota between the rumen of sheep and the cecum
      of rabbits. Hydrogen-producing fibrolytic bacteria, especially Butyrivibrio,
      Succiniclastium, Mogibacterium, Prevotella, and Christensenellaceae, were more
      predominant in the sheep rumen, whereas non-hydrogen producing fibrolytic
      bacteria, such as Bacteroides, were more predominant in the rabbit cecum. The
      rabbit cecum had a greater predominance of acetogens, such as those in the genus
      Blautia, order Clostridiales, and family Ruminococcaceae. The differences in the
      occurrence of hydrogen-metabolizing bacteria probably explain much of the
      differential methane outputs from the rumen and the cecum. Future research using
      metatranscriptomics and metabolomics shall help confirm this premise and
      understand the factors that shape the differential microbiota between the two
      digestive organs. Furthermore, our present study strongly suggests the presence
      of new fibrolytic bacteria in the rabbit cecum, which may explain the stronger
      fibrolytic activities therein.

PMID- 29662481
TI  - Listeria monocytogenes Sequence Types 121 and 14 Repeatedly Isolated Within One
      Year of Sampling in a Rabbit Meat Processing Plant: Persistence and
      Ecophysiology.
AB  - Listeria monocytogenes is a foodborne pathogen adapted to survive and persist in
      multiple environments. Following two previous studies on prevalence and virulence
      of L. monocytogenes ST121 and ST14 repeatedly collected in a the same rabbit-meat
      processing plant, the research questions of the present study were to: (1) assess
      persistence of L. monocytogenes isolates from the rabbit-plant; (2) select genes
      associated to physiological adaptation to the food-processing environment; (3)
      compare presence/absence/truncation of these genes in newly sequenced and
      publicly available ST121 and ST14 genomes. A total of 273 draft genomes including
      ST121 and ST14 newly sequenced and publicly available draft genomes were
      analyzed. Whole-genome Single Nucleotide Polymorfism (wgSNP) analysis was
      performed separately on the assemblies of ST121 and ST14 draft genomes. SNPs
      alignments were used to infer phylogeny. A dataset of L. monocytogenes
      ecophysiology genes was built based on a comprehensive literature review. The 94
      selected genes were screened on the assemblies of all ST121 and ST14 draft
      genomes. Significant gene enrichments were evaluated by statistical analyses. A
      persistent ST14 clone, including 23 out of 27 newly sequenced genomes, was
      circulating in the rabbit-meat plant along with two not persistent clones. A
      significant enrichment was observed in ST121 genomes concerning stress survival
      islet 2 (SSI-2) (alkaline and oxidative stress), qacH gene (resistance to
      benzalkonium chloride), cadA1C gene cassette (resistance to 70 mg/l of cadmium
      chloride) and a truncated version of actA gene (biofilm formation). Conversely,
      ST14 draft genomes were enriched with a full-length version of actA gene along
      with the Listeria Genomic Island 2 (LGI 2) including the ars operon (arsenic
      resistance) and the cadA4C gene cassette (resistance to 35 mg/l of cadmium
      chloride). Phenotypic tests confirmed ST121 as a weak biofilm producer in
      comparison to ST14. In conclusion, ST121 carried the qacH gene and was
      phenotypically resistant to quaternary ammonium compounds. This property might
      contribute to the high prevalence of ST121 in food processing plants. ST14 showed
      greater ability to form biofilms, which might contribute to the occasional
      colonization and persistence on harborage sites where sanitizing procedures are
      difficult to display.

PMID- 29662482
TI  - Targeting Mycobacterium tuberculosis Antigens to Dendritic Cells via the DC
      Specific-ICAM3-Grabbing-Nonintegrin Receptor Induces Strong T-Helper 1 Immune
      Responses.
AB  - Tuberculosis remains a major global health problem and efforts to develop a more
      effective vaccine have been unsuccessful so far. Targeting antigens (Ags) to
      dendritic cells (DCs) in vivo has emerged as a new promising vaccine strategy. In
      this approach, Ags are delivered directly to DCs via antibodies that bind to
      endocytic cell-surface receptors. Here, we explored DC-specific-ICAM3-grabbing
      nonintegrin (DC-SIGN) targeting as a potential vaccine against tuberculosis. For
      this, we made use of the hSIGN mouse model that expresses human DC-SIGN under the
      control of the murine CD11c promoter. We show that in vitro and in vivo delivery
      of anti-DC-SIGN antibodies conjugated to Ag85B and peptide 25 of Ag85B in
      combination with anti-CD40, the fungal cell wall component zymosan, and the
      cholera toxin-derived fusion protein CTA1-DD induces strong Ag-specific CD4+ T
      cell responses. Improved anti-mycobacterial immunity was accompanied by increased
      frequencies of Ag-specific IFN-gamma+ IL-2+ TNF-alpha+ polyfunctional CD4+ T
      cells in vaccinated mice compared with controls. Taken together, in this study we
      provide the proof of concept that the human DC-SIGN receptor can be efficiently
      exploited for vaccine purposes to promote immunity against mycobacterial
      infections.

PMID- 29662483
TI  - Long Non-Coding RNA HOXA Transcript Antisense RNA Myeloid-Specific 1-HOXA1 Axis
      Downregulates the Immunosuppressive Activity of Myeloid-Derived Suppressor Cells
      in Lung Cancer.
AB  - HOXA transcript antisense RNA myeloid-specific 1 (HOTAIRM1) is a long non-coding
      RNA that has been shown to be a key regulator of myeloid cell development by
      targeting HOXA1. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous
      population of immature myeloid cells that possess immunosuppressive function.
      However, the impact of HOTAIRM1 on the development of MDSCs remains unknown. In
      this study, we demonstrated that HOTAIRM1 was expressed in MDSCs and that
      overexpression of HOTAIRM1 could downregulate the expression of suppressive
      molecules in MDSCs. In addition, HOTAIRM1 levels were observed to be decreased in
      the peripheral blood cells of lung cancer patients compared with those of healthy
      controls. By analyzing HOTAIRM1 expression levels in different types of lung
      cancer, we found that HOTAIRM1 was mainly expressed in lung adenocarcinoma.
      Finally, it was confirmed that HOTAIRM1 could enhance the expression of HOXA1 in
      MDSCs and that high levels of HOXA1, the target gene of HOTAIRM1, could delay
      tumor progression and enhance the antitumor immune response by downregulating the
      immunosuppression of MDSCs. Taken together, this study illustrates that
      HOTAIRM1/HOXA1 downregulates the immunosuppressive function of MDSCs and may be a
      potential therapeutic target in lung cancer.

PMID- 29662484
TI  - NKG2D and Its Ligands: "One for All, All for One".
AB  - The activating receptor NKG2D is peculiar in its capability to bind to numerous
      and highly diversified MHC class I-like self-molecules. These ligands are poorly
      expressed on normal cells but can be induced on damaged, transformed or infected
      cells, with the final NKG2D ligand expression resulting from multiple levels of
      regulation. Although redundant molecular mechanisms can converge in the
      regulation of all NKG2D ligands, different stimuli can induce specific cellular
      responses, leading to the expression of one or few ligands. A large body of
      evidence demonstrates that NK cell activation can be triggered by different NKG2D
      ligands, often expressed on the same cell, suggesting a functional redundancy of
      these molecules. However, since a number of evasion mechanisms can reduce
      membrane expression of these molecules both on virus-infected and tumor cells,
      the co-expression of different ligands and/or the presence of allelic forms of
      the same ligand guarantee NKG2D activation in various stressful conditions and
      cell contexts. Noteworthy, NKG2D ligands can differ in their ability to down
      modulate NKG2D membrane expression in human NK cells supporting the idea that
      NKG2D transduces different signals upon binding various ligands. Moreover,
      whether proteolytically shed and exosome-associated soluble NKG2D ligands share
      with their membrane-bound counterparts the same ability to induce NKG2D-mediated
      signaling is still a matter of debate. Here, we will review recent studies on the
      NKG2D/NKG2D ligand biology to summarize and discuss the redundancy and/or
      diversity in ligand expression, regulation, and receptor specificity.

PMID- 29662486
TI  - Mucosal Involvement in Bullous Pemphigoid Is Mostly Associated with Disease
      Severity and to Absence of Anti-BP230 Autoantibody.
AB  - Bullous pemphigoid (BP) is the most common autoimmune bullous disease and
      typically affects the elderly. Binding of specific autoantibodies to BP180/230
      hemidesmosomal components induces an inflammatory response leading to skin
      blister formation. Unusual manifestations of BP include additional mucous
      membrane involvement, without pathophysiological knowledge associated to the
      formation of these lesions. We here performed a prospective study on series of
      consecutive BP patients with (n = 77) and without (n = 18) mucosal involvements
      at baseline to further investigate why some BP patients display mucosal lesion
      and other not. Analysis of disease activity showed that BP patients with mucosal
      involvement displayed a higher total BP Disease Area Index (BPDAI) score (P =
      0.008), but also higher skin and blister/erosion BPDAI scores (P = 0.02 and P =
      0.001, respectively). By contrast, the erythema/urticaria BPDAI score was
      identical between the two groups of patients. The erythema/urticaria BPDAI score,
      but not the blister/erosion BPDAI score, was correlated with the serum
      concentration of anti-BP180 NC16A autoantibodies in patients with mucosal
      involvement. In multivariate analysis, the absence of anti-BP230 autoantibody was
      the only factor independently associated with mucosal involvement (OR 7.8; 95%
      CI, 3.1-19.6) (P < 0.0001). Analysis of the distribution of BP patients according
      to BPDAI scores revealed a shift toward higher blister/erosion BPDAI scores for
      BP patients with mucosal involvement. This study indicates that mucosal lesions
      are clinically mainly related to disease severity and immunologically to the
      absence of anti-BP230 antibodies.

PMID- 29662485
TI  - Our Environment Shapes Us: The Importance of Environment and Sex Differences in
      Regulation of Autoantibody Production.
AB  - Consequential differences exist between the male and female immune systems'
      ability to respond to pathogens, environmental insults or self-antigens, and
      subsequent effects on immunoregulation. In general, females when compared with
      their male counterparts, respond to pathogenic stimuli and vaccines more
      robustly, with heightened production of antibodies, pro-inflammatory cytokines,
      and chemokines. While the precise reasons for sex differences in immune response
      to different stimuli are not yet well understood, females are more resistant to
      infectious diseases and much more likely to develop autoimmune diseases.
      Intrinsic (i.e., sex hormones, sex chromosomes, etc.) and extrinsic (microbiome
      composition, external triggers, and immune modulators) factors appear to impact
      the overall outcome of immune responses between sexes. Evidence suggests that
      interactions between environmental contaminants [e.g., endocrine disrupting
      chemicals (EDCs)] and host leukocytes affect the ability of the immune system to
      mount a response to exogenous and endogenous insults, and/or return to normal
      activity following clearance of the threat. Inherently, males and females have
      differential immune response to external triggers. In this review, we describe
      how environmental chemicals, including EDCs, may have sex differential influence
      on the outcome of immune responses through alterations in epigenetic status (such
      as modulation of microRNA expression, gene methylation, or histone modification
      status), direct and indirect activation of the estrogen receptors to drive
      hormonal effects, and differential modulation of microbial sensing and
      composition of host microbiota. Taken together, an intriguing question develops
      as to how an individual's environment directly and indirectly contributes to an
      altered immune response, dysregulation of autoantibody production, and influence
      autoimmune disease development. Few studies exist utilizing well-controlled
      cohorts of both sexes to explore the sex differences in response to EDC exposure
      and the effects on autoimmune disease development. Translational studies
      incorporating multiple environmental factors in animal models of autoimmune
      disease are necessary to determine the interrelationships that occur between
      potential etiopathological factors. The presence or absence of autoantibodies is
      not a reliable predictor of disease. Therefore, future studies should incorporate
      all the susceptibility/influencing factors, coupled with individual genomics,
      epigenomics, and proteomics, to develop a model that better predicts, diagnoses,
      and treats autoimmune diseases in a personalized-medicine fashion.

PMID- 29662487
TI  - Acquisition of N-Glycosylation Sites in Immunoglobulin Heavy Chain Genes During
      Local Expansion in Parotid Salivary Glands of Primary Sjogren Patients.
AB  - Previous studies revealed high incidence of acquired N-glycosylation sites
      acquired N-glycosylation sites in RNA transcripts encoding immunoglobulin heavy
      variable region (IGHV) 3 genes from parotid glands of primary Sjogren's syndrome
      (pSS) patients. In this study, next generation sequencing was used to study the
      extent of ac-Nglycs among clonally expanded cells from all IGVH families in the
      salivary glands of pSS patients. RNA was isolated from parotid gland biopsies of
      five pSS patients and five non-pSS sicca controls. IGHV sequences covering all
      functional IGHV genes were amplified, sequenced, and analyzed. Each biopsy
      recovered 1,800-4,000 unique IGHV sequences. No difference in IGHV gene usage was
      observed between pSS and non-pSS sequences. Clonally related sequences with more
      than 0.3% of the total number of sequences per patient were referred to as
      dominant clone. Overall, 70 dominant clones were found in pSS biopsies, compared
      to 15 in non-pSS. No difference in percentage mutation in dominant clone-derived
      IGHV sequences was seen between pSS and non-pSS. In pSS, no evidence for antigen
      driven selection in dominant clones was found. We observed a significantly higher
      amount of ac-Nglycs among pSS dominant clone-derived sequences compared to non
      pSS. Ac-Nglycs were, however, not restricted to dominant clones or IGHV gene.
      Most ac-Nglycs were detected in the framework 3 region. No stereotypic rheumatoid
      factor rearrangements were found in dominant clones. Lineage tree analysis showed
      in four pSS patients, but not in non-pSS, the presence of the germline sequence
      from a dominant clone. Presence of germline sequence and mutated IGHV sequences
      in the same dominant clone provide evidence that this clone originated from a
      naive B-cell recruited into the parotid gland to expand and differentiate locally
      into plasma cells. The increased presence of ac-Nglycs in IGHV sequences, due to
      somatic hypermutation, might provide B-cells an escape mechanism to survive
      during immune response. We speculate that glycosylation of the B-cell receptor
      makes the cell sensitive to environmental lectin signals to contribute to
      aberrant B-cell selection in pSS parotid glands.

PMID- 29662488
TI  - Subretinal Injection of HY Peptides Induces Systemic Antigen-Specific Inhibition
      of Effector CD4+ and CD8+ T-Cell Responses.
AB  - Purpose: Injection of an antigen into the anterior chamber of the eye induces a
      peripheral antigen-specific immune modulation mechanism, known as anterior
      chamber-associated immune deviation (ACAID). Delayed-type hypersensitivity
      experiments argue that the subretinal space (SR) of the eye displays properties
      similar to ACAID. However, no investigation was performed regarding the
      differential impact of a subretinal antigen injection on peripheral CD4+ versus
      CD8+ T cells, on the potential immune deviation regarding Th profiles, and on the
      antigen-specificity of the inhibition. A better understanding of these mechanisms
      is crucial to improve safety and immunomonitoring of ongoing therapeutic
      approaches targeting the SR. The aim of this study is to characterize the
      proliferative capacities and cytokine patterns of antigen-specific CD4+ and CD8+
      T cells after a subretinal injection of antigen in mice. Methods: Ubiquitously
      Transcribed tetratricopeptide repeat gene Y-linked (UTY) and DEAD Box polypeptide
      3 Y-linked (DBY) peptides which respectively include MHCI- and MHCII-restricted T
      cell epitopes of the mouse HY male antigen, were injected into the subretinal
      space of C57BL/6 female mice. 2 weeks later, these mice were immunized
      subcutaneously with these peptides and compared to control mice. A week later, T
      cell immune responses were analyzed by IFNgamma ELISpot assays and cytokine
      measurements (IL-2, IL-4, IL-6, IL-10, IL-13, IL-17a, IFNgamma, TNFalpha, GM-CSF,
      and MCP-1) in the spleen and with proliferation assays in draining lymph nodes.
      Results: Immune cells from mice that received HY peptides in the SR before
      immunization, compared with those from control immunized mice, secreted
      significantly smaller quantities of Th1/Tc1, Th2/Tc2, and Th17/Tc17 cytokines,
      and HY-specific CD4+ T cells proliferated less in response to HY peptides.
      Conclusion: Taken together, our data clearly demonstrate that the subretinal
      injection of HY peptides induces a systemic HY-specific inhibition of
      conventional Th profiles and CD8+ T cells. We propose to call this phenomenon
      SRAII, for subretinal-associated immune inhibition.

PMID- 29662490
TI  - mTOR at the Transmitting and Receiving Ends in Tumor Immunity.
AB  - Cancer is a complex disease and a leading cause of death worldwide. Immunity is
      critical for cancer control. Cancer cells exhibit high mutational rates and
      therefore altered self or neo-antigens, eliciting an immune response to promote
      tumor eradication. Failure to mount a proper immune response leads to cancer
      progression. mTOR signaling controls cellular metabolism, immune cell
      differentiation, and effector function. Deregulated mTOR signaling in cancer
      cells modulates the tumor microenvironment, thereby affecting tumor immunity and
      possibly promoting carcinogenesis.

PMID- 29662489
TI  - Immunological Approaches Towards Cancer and Inflammation: A Cross Talk.
AB  - The inflammation is the protective response of the body against various harmful
      stimuli; however, the aberrant and inappropriate activation tends to become
      harmful. The acute inflammatory response tends to resolved once the offending
      agent is subside but this acute response becomes chronic in nature when the body
      is unable to successfully neutralized the noxious stimuli. This chronic
      inflammatory microenvironment is associated with the release of various pro
      inflammatory and oncogenic mediators such as nitric oxide (NO), cytokines [IL
      1beta, IL-2, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha)],
      growth factor, and chemokines. These mediators make the inflammatory
      microenvironment more vulnerable toward tumorigenesis. The pro-inflammatory
      mediators released during the chronic inflammation tends to induce several
      molecular signaling cascades such as nuclear factor kappa B, MAPKinase, nuclear
      factor erythroid 2-related factor 2, phosphoinositide-3-kinase, Janus
      kinases/STAT, Wnt/B-catenin, and cyclic AMP response element binding protein. The
      immune system and its components have a pleiotropic effect on inflammation and
      cancer progression. Immune components such as T cells, natural killer cells,
      macrophages, and neutrophils either inhibit or enhance tumor initiation depending
      on the type of tumor and immune cells involved. Tumor-associated macrophages and
      tumor-associated neutrophils are pro-tumorigenic cells highly prevalent in
      inflammation-mediated tumors. Similarly, presence of T regulatory (Treg) cells in
      an inflammatory and tumor setting suppresses the immune system, thus paving the
      way for oncogenesis. However, Treg cells also inhibit autoimmune inflammation. By
      contrast, cytotoxic T cells and T helper cells confer antitumor immunity and are
      associated with better prognosis in patients with cancer. Cytotoxic T cells
      inflict a direct cytotoxic effect on cells expressing oncogenic markers.
      Currently, several anti-inflammatory and antitumor therapies are under trials in
      which these immune cells are exploited. Adoptive cell transfer composed of tumor
      infiltrating lymphocytes has been tried for the treatment of tumors after their
      ex vivo expansion. Mediators released by cells in a tumorigenic and inflammatory
      microenvironment cross talk with nearby cells, either promoting or inhibiting
      inflammation and cancer. Recently, several cytokine-based therapies are either
      being developed or are under trial to treat such types of manifestations.
      Monoclonal antibodies directed against TNF-alpha, VEGF, and IL-6 has shown
      promising results to ameliorate inflammation and cancer, while direct
      administration of IL-2 has been shown to cause tumor regression.

PMID- 29662491
TI  - Regulatory T-Cells: Potential Regulator of Tissue Repair and Regeneration.
AB  - The identification of stem cells and growth factors as well as the development of
      biomaterials hold great promise for regenerative medicine applications. However,
      the therapeutic efficacy of regenerative therapies can be greatly influenced by
      the host immune system, which plays a pivotal role during tissue repair and
      regeneration. Therefore, understanding how the immune system modulates tissue
      healing is critical to design efficient regenerative strategies. While the innate
      immune system is well known to be involved in the tissue healing process, the
      adaptive immune system has recently emerged as a key player. T-cells, in
      particular, regulatory T-cells (Treg), have been shown to promote repair and
      regeneration of various organ systems. In this review, we discuss the mechanisms
      by which Treg participate in the repair and regeneration of skeletal and heart
      muscle, skin, lung, bone, and the central nervous system.

PMID- 29662492
TI  - RNase H2 Loss in Murine Astrocytes Results in Cellular Defects Reminiscent of
      Nucleic Acid-Mediated Autoinflammation.
AB  - Aicardi-Goutieres syndrome (AGS) is a rare early onset childhood encephalopathy
      caused by persistent neuroinflammation of autoimmune origin. AGS is a genetic
      disorder and >50% of affected individuals bear hypomorphic mutations in
      ribonuclease H2 (RNase H2). All available RNase H2 mouse models so far fail to
      mimic the prominent CNS involvement seen in AGS. To establish a mouse model
      recapitulating the human disease, we deleted RNase H2 specifically in the brain,
      the most severely affected organ in AGS. Although RNase H2DeltaGFAP mice lacked
      the nuclease in astrocytes and a majority of neurons, no disease signs were
      apparent in these animals. We additionally confirmed these results in a second,
      neuron-specific RNase H2 knockout mouse line. However, when astrocytes were
      isolated from brains of RNase H2DeltaGFAP mice and cultured under mitogenic
      conditions, they showed signs of DNA damage and premature senescence. Enhanced
      expression of interferon-stimulated genes (ISGs) represents the most reliable AGS
      biomarker. Importantly, primary RNase H2DeltaGFAP astrocytes displayed
      significantly increased ISG transcript levels, which we failed to detect in in
      vivo in brains of RNase H2DeltaGFAP mice. Isolated astrocytes primed by DNA
      damage, including RNase H2-deficiency, exhibited a heightened innate immune
      response when exposed to bacterial or viral antigens. Taken together, we
      established a valid cellular AGS model that utilizes the very cell type
      responsible for disease pathology, the astrocyte, and phenocopies major molecular
      defects observed in AGS patient cells.

PMID- 29662493
TI  - Age-Related Changes in the Natural Killer Cell Response to Seasonal Influenza
      Vaccination Are Not Influenced by a Synbiotic: a Randomised Controlled Trial.
AB  - : Natural killer (NK) cells are an important component of the immune response to
      influenza infection, but are subject to alteration during aging, which may play a
      role in impaired response to infection and vaccination in older people.
      Enhancement of NK cell activity could, therefore, present a means to improve the
      immune response to vaccination in older subjects, and pre- and probiotics offer
      an opportunity to modulate antiviral defenses via alteration of the gut
      microbiota. This study investigated the effect of a novel probiotic,
      Bifidobacterium longum bv. infantis CCUG 52486, combined with a prebiotic, gluco
      oligosaccharide (B. longum + Gl-OS), on the NK cell response to seasonal
      influenza vaccination in young and older subjects in a double-blind, randomized
      controlled trial. There were significant effects of aging on NK cell phenotype,
      the most notable of which were an increase in CD56dim cells, mainly reflected in
      the CD16+ subset, a decrease in CD56bright cells, mainly reflected in the CD16-
      subset, and greater expression of the immunosenescence marker, CD57, on NK cell
      subsets. However, these changes only partially translated to differences in NK
      cell activity, observed as trends toward reduced NK cell activity in older
      subjects when analyzed on a per cell basis. Influenza vaccination increased the
      proportion of CD56bright cells and decreased the proportion of CD56dim cells, in
      young, but not older subjects. Although NK cell activity in response to
      vaccination was not significantly different between the young and older subjects,
      low post-vaccination NK cell activity was associated with poor seroconversion in
      only the older subjects. There was no influence of the synbiotic on NK cell
      phenotype or activity, either before or after influenza vaccination. In
      conclusion, aging is associated with marked alteration of the phenotype of the NK
      cell population and there was evidence of an impaired NK cell response to
      influenza vaccination in older subjects. The effects of aging on NK cell
      phenotype and activity could not be offset by B. longum + Gl-OS. Clinical Trial
      Registration: www.ClinicalTrials.gov, identifier NCT01066377.

PMID- 29662494
TI  - Evolution of Neutralization Response in HIV-1 Subtype C-Infected Individuals
      Exhibiting Broad Cross-Clade Neutralization of HIV-1 Strains.
AB  - Strain-specific neutralizing antibodies develop in all human immunodeficiency
      virus type 1 (HIV-1)-infected individuals. However, only 10-30% of infected
      individuals produce broadly neutralizing antibodies (bNAbs). Identification and
      characterization of these bNAbs and understanding their evolution dynamics are
      critical for obtaining useful clues for the development of an effective HIV
      vaccine. Very recently, we published a study in which we identified 12 HIV-1
      subtype C-infected individuals from India whose plasma showed potent and broad
      cross-clade neutralization (BCN) ability (1). In the present study, we report our
      findings on the evolution of host bNAb response over a period of 4 years in a
      subset of these individuals. Three of the five individuals (NAB033, NAB059, and
      NAB065) demonstrated a significant increase (p < 0.05) in potency. Interestingly,
      two of the three samples also showed a significant increase in CD4 binding site
      specific antibody response, maintained stable CD4+ T cell counts (>350 cells/mm3)
      and continued to remain ART-naive for more than 10 years after initial diagnosis,
      implying a strong clinical correlation with the development and evolution of
      broadly neutralizing antibody response against HIV-1.

PMID- 29662495
TI  - Comparative Analysis of WUSCHEL-Related Homeobox Genes Revealed Their Parent-of
      Origin and Cell Type-Specific Expression Pattern During Early Embryogenesis in
      Tobacco.
AB  - WUSCHEL-related homeobox (WOX) gene is a plant-specific clade of homeobox
      transcription factors. Increasing evidences reveal that WOXs play critical roles
      in early embryogenesis, which involves zygote development, initiation of zygote
      division, and apical or basal cell lineage establishment. However, how WOXs
      regulate these developmental events remains largely unknown, and even detailed
      expression pattern in gametes and early proembryos is not yet available. Here, 13
      WOX family genes were identified in Nicotiana tabacum genome. Comparative
      analysis of 13 WOX family genes with their homologs in Arabidopsis thaliana
      reveals relatively conserved expression pattern of WUS and WOX5 in shoot/root
      apical meristem. Whereas variations were also found, e.g., lacking homolog of
      WOX8 (a marker for suspensor cell) in tobacco genome and the expression of
      WOX2/WOX9 in both apical cell and basal cell. Transient transcriptional activity
      analysis revealed that WOXs in WUS clade have repressive activities for their
      target's transcription, whereas WOXs in ancient and intermediate clade have
      activation activities, giving a molecular basis for the phylogenetic
      classification of tobacco WOXs into three major clades. Expression pattern
      analysis revealed that some WOXs (e.g., WOX 13a) expressed in both male and
      female gametes and some WOXs (e.g., WOX 11 and WOX 13b) displayed the
      characteristics of parent-of-origin genes. Interestingly, some WOXs (e.g., WOX2
      and WOX9), which are essential for early embryo patterning, were de novo
      transcribed in zygote, indicating relevant mechanism for embryo pattern formation
      is only established in zygote right after fertilization and not carried in by
      gametes. We also found that most WOXs displayed a stage-specific and cell type
      specific expression pattern. Taken together, this work provides a detailed
      landscape of WOXs in tobacco during fertilization and early embryogenesis, which
      will facilitate the understanding of their specific roles in these critical
      developmental processes of embryogenesis.

PMID- 29662497
TI  - Prediction of Cacao (Theobroma cacao) Resistance to Moniliophthora spp. Diseases
      via Genome-Wide Association Analysis and Genomic Selection.
AB  - Cacao (Theobroma cacao) is a globally important crop, and its yield is severely
      restricted by disease. Two of the most damaging diseases, witches' broom disease
      (WBD) and frosty pod rot disease (FPRD), are caused by a pair of related fungi:
      Moniliophthora perniciosa and Moniliophthora roreri, respectively. Resistant
      cultivars are the most effective long-term strategy to address Moniliophthora
      diseases, but efficiently generating resistant and productive new cultivars will
      require robust methods for screening germplasm before field testing. Marker
      assisted selection (MAS) and genomic selection (GS) provide two potential avenues
      for predicting the performance of new genotypes, potentially increasing the
      selection gain per unit time. To test the effectiveness of these two approaches,
      we performed a genome-wide association study (GWAS) and GS on three related
      populations of cacao in Ecuador genotyped with a 15K single nucleotide
      polymorphism (SNP) microarray for three measures of WBD infection (vegetative
      broom, cushion broom, and chirimoya pod), one of FPRD (monilia pod) and two
      productivity traits (total fresh weight of pods and % healthy pods produced).
      GWAS yielded several SNPs associated with disease resistance in each population,
      but none were significantly correlated with the same trait in other populations.
      Genomic selection, using one population as a training set to estimate the
      phenotypes of the remaining two (composed of different families), varied among
      traits, from a mean prediction accuracy of 0.46 (vegetative broom) to 0.15
      (monilia pod), and varied between training populations. Simulations demonstrated
      that selecting seedlings using GWAS markers alone generates no improvement over
      selecting at random, but that GS improves the selection process significantly.
      Our results suggest that the GWAS markers discovered here are not sufficiently
      predictive across diverse germplasm to be useful for MAS, but that using all
      markers in a GS framework holds substantial promise in accelerating disease
      resistance in cacao.

PMID- 29662496
TI  - Assembly and Transfer of Iron-Sulfur Clusters in the Plastid.
AB  - Iron-Sulfur (Fe-S) clusters and proteins are essential to many growth and
      developmental processes. In plants, they exist in the plastids, mitochondria,
      cytosol, and nucleus. Six types of Fe-S clusters are found in the plastid:
      classic 2Fe-2S, NEET-type 2Fe-2S, Rieske-type 2Fe-2S, 3Fe-4S, 4Fe-4S, and
      siroheme 4Fe-4S. Classic, NEET-type, and Rieske-type 2Fe-2S clusters have the
      same 2Fe-2S core; similarly, common and siroheme 4Fe-4S clusters have the same
      4Fe-4S core. Plastidial Fe-S clusters are assembled by the sulfur mobilization
      (SUF) pathway, which contains cysteine desulfurase (EC 2.8.1.7), sulfur
      transferase (EC 2.8.1.3), Fe-S scaffold complex, and Fe-S carrier proteins. The
      plastidial cysteine desulfurase-sulfur transferase-Fe-S-scaffold complex system
      is responsible for de novo assembly of all plastidial Fe-S clusters. However,
      different types of Fe-S clusters are transferred to recipient proteins via
      respective Fe-S carrier proteins. This review focuses on recent discoveries on
      the molecular functions of different assembly and transfer factors involved in
      the plastidial SUF pathway. It also discusses potential points for regulation of
      the SUF pathway, relationships among the plastidial, mitochondrial, and cytosolic
      Fe-S assembly and transfer pathways, as well as several open questions about the
      carrier proteins for Rieske-type 2Fe-2S, NEET-type 2Fe-2S, and 3F-4S clusters.

PMID- 29662498
TI  - Small RNA and Degradome Deep Sequencing Reveals the Roles of microRNAs in Seed
      Expansion in Peanut (Arachis hypogaea L.).
AB  - Seed expansion in peanut is a complex biological process involving many gene
      regulatory pathways. MicroRNAs (miRNAs) play important regulatory roles in plant
      growth and development, but little is known about their functions during seed
      expansion, or how they contribute to seed expansion in different peanut lines. We
      examined seed miRNA expression patterns at 15 and 35 days after flowering (DAF)
      in two peanut eighth-generation recombinant inbred lines (RIL8); 8106, a medium
      pod variety, and 8107, a super-pod variety. Using high-throughput sequencing, we
      identified 1,082 miRNAs in developing peanut seeds including 434 novel miRNAs. We
      identified 316 differentially expressed miRNAs by comparing expression levels
      between the two peanut lines. Interestingly, 24 miRNAs showed contrasting
      patterns of expression in the two RILs, and 149 miRNAs were expressed
      predominantly in only one RIL at 35 DAF. Also, potential target genes for some
      conserved and novel miRNAs were identified by degradome sequencing; target genes
      were predicted to be involved in auxin mediated signaling pathways and cell
      division. We validated the expression patterns of some representative miRNAs and
      12 target genes by qPCR, and found negative correlations between the expression
      level of miRNAs and their targets. miR156e, miR159b, miR160a, miR164a, miR166b,
      miR168a, miR171n, miR172c-5p, and miR319d and their corresponding target genes
      may play key roles in seed expansion in peanut. The results of our study also
      provide novel insights into the dynamic changes in miRNAs that occur during
      peanut seed development, and increase our understanding of miRNA function in seed
      expansion.

PMID- 29662499
TI  - NAD Kinases: Metabolic Targets Controlling Redox Co-enzymes and Reducing Power
      Partitioning in Plant Stress and Development.
AB  - NAD(H) and NADP(H) are essential co-enzymes which dominantly control a number of
      fundamental biological processes by acting as reducing power and maintaining the
      intracellular redox balance of all life kingdoms. As the only enzymes that
      catalyze NAD(H) and ATP to synthesize NADP(H), NAD Kinases (NADKs) participate in
      many essential metabolic reactions, redox sensitive regulation, photosynthetic
      performance and also reactive oxygen species (ROS) homeostasis of cells and
      therefore, play crucial roles in both development and stress responses of plants.
      NADKs are highly conserved enzymes in amino acid sequences but have multiple
      subcellular localization and diverse functions. They may function as monomers,
      dimers or multimers in cells but the enzymatic properties in plants are not well
      elucidated yet. The activity of plant NADK is regulated by calcium/calmodulin and
      plays crucial roles in photosynthesis and redox co-enzyme control. NADK genes are
      expressed in almost all tissues and developmental stages of plants with
      specificity for different members. Their transcripts can be greatly stimulated by
      a number of environmental factors such as pathogenic attack, irritant
      applications and abiotic stress treatments. Using transgenic approaches, several
      studies have shown that NADKs are involved in chlorophyll synthesis,
      photosynthetic efficiency, oxidative stress protection, hormone metabolism and
      signaling regulation, and therefore contribute to the growth regulation and
      stress tolerance of plants. In this review, the enzymatic properties and
      functional mechanisms of plant NADKs are thoroughly investigated based on
      literature and databases. The results obtained here are greatly advantageous for
      further exploration of NADK function in plants.

PMID- 29662500
TI  - Genetic Resources in the "Calabaza Pipiana" Squash (Cucurbita argyrosperma) in
      Mexico: Genetic Diversity, Genetic Differentiation and Distribution Models.
AB  - Analyses of genetic variation allow understanding the origin, diversification and
      genetic resources of cultivated plants. Domesticated taxa and their wild
      relatives are ideal systems for studying genetic processes of plant domestication
      and their joint is important to evaluate the distribution of their genetic
      resources. Such is the case of the domesticated subspecies C. argyrosperma ssp.
      argyrosperma, known in Mexico as calabaza pipiana, and its wild relative C.
      argyrosperma ssp. sororia. The main aim of this study was to use molecular data
      (microsatellites) to assess the levels of genetic variation and genetic
      differentiation within and among populations of domesticated argyrosperma across
      its distribution in Mexico in comparison to its wild relative, sororia, and to
      identify environmental suitability in previously proposed centers of
      domestication. We analyzed nine unlinked nuclear microsatellite loci to assess
      levels of diversity and distribution of genetic variation within and among
      populations in 440 individuals from 19 populations of cultivated landraces of
      argyrosperma and from six wild populations of sororia, in order to conduct a
      first systematic analysis of their genetic resources. We also used species
      distribution models (SDMs) for sororia to identify changes in this wild
      subspecies' distribution from the Holocene (~6,000 years ago) to the present, and
      to assess the presence of suitable environmental conditions in previously
      proposed domestication sites. Genetic variation was similar among subspecies (HE
      = 0.428 in sororia, and HE = 0.410 in argyrosperma). Nine argyrosperma
      populations showed significant levels of inbreeding. Both subspecies are well
      differentiated, and genetic differentiation (FST) among populations within each
      subspecies ranged from 0.152 to 0.652. Within argyrosperma we found three genetic
      groups (Northern Mexico, Yucatan Peninsula, including Michoacan and Veracruz, and
      Pacific coast plus Durango). We detected low levels of gene flow among
      populations at a regional scale (<0.01), except for the Yucatan Peninsula, and
      the northern portion of the Pacific Coast. Our analyses suggested that the
      Isthmus of Tehuantepec is an effective barrier isolating southern populations.
      Our SDM results indicate that environmental characteristics in the Balsas-Jalisco
      region, a potential center of domestication, were suitable for the presence of
      sororia during the Holocene.

PMID- 29662501
TI  - Species Boundaries Between Three Sympatric Oak Species: Quercus aliena, Q.
      dentata, and Q. variabilis at the Northern Edge of Their Distribution in China.
AB  - Oaks are important timber trees with wide distributions in China, but few genetic
      studies have been conducted on a fine scale. In this study, we seek to
      investigate the genetic diversity and differentiation of three sympatric oak
      species (Quercus aliena Blume, Quercus dentata Thunb. ex Murray, and Quercus
      variabilis Blume) in their northern distribution in China using 17 bi-parentally
      inherited nSSRs markers and five maternally inherited chloroplast DNA (cpDNA)
      fragments. Both the cpDNA and the nSSRs show a high level of genetic
      differentiation between different oak sections. The chloroplast haplotypes are
      clustered into two lineages. Clear species boundaries are detected between Q.
      variabilis and either Q. aliena or Q. dentata. The sharing of chloroplast
      haplotype H1 between Q. aliena and Q. dentata suggests very recent speciation and
      incomplete lineage sorting or introgression of H1 from one species to another.
      The nSSRs data indicate a complete fixation of variation within sites for all
      three oak species, and that extensive gene flow occurs within species whereas
      only limited gene flow is detected between Q. aliena and Q. dentata and nearly no
      gene flow can be detected between Q. aliena and Q. variabilis and between Q.
      dentata and Q. variabilis. Prezygotic isolation may have contributed to the
      species boundaries of these three sympatric oak species.

PMID- 29662503
TI  - Identification and Functional Analysis of Long Intergenic Non-coding RNAs
      Underlying Intramuscular Fat Content in Pigs.
AB  - Intramuscular fat (IMF) content is an important trait that can affect pork
      quality. Previous studies have identified many genes that can regulate IMF. Long
      intergenic non-coding RNAs (lincRNAs) are emerging as key regulators in various
      biological processes. However, lincRNAs related to IMF in pig are largely
      unknown, and the mechanisms by which they regulate IMF are yet to be elucidated.
      Here we reconstructed 105,687 transcripts and identified 1,032 lincRNAs in pig
      longissimus dorsi muscle (LDM) of four stages with different IMF contents based
      on published RNA-seq. These lincRNAs show typical characteristics such as shorter
      length and lower expression compared with protein-coding genes. Combined with
      methylation data, we found that both the promoter and genebody methylation of
      lincRNAs can negatively regulate lincRNA expression. We found that lincRNAs
      exhibit high correlation with their protein-coding neighbors in expression. Co
      expression network analysis resulted in eight stage-specific modules, gene
      ontology and pathway analysis of them suggested that some lincRNAs were involved
      in IMF-related processes, such as fatty acid metabolism and peroxisome
      proliferator-activated receptor signaling pathway. Furthermore, we identified hub
      lincRNAs and found six of them may play important roles in IMF development. This
      work detailed some lincRNAs which may affect of IMF development in pig, and
      facilitated future research on these lincRNAs and molecular assisted breeding for
      pig.

PMID- 29662502
TI  - Sex-Dependent Effects of Developmental Lead Exposure on the Brain.
AB  - The role of sex as an effect modifier of developmental lead (Pb) exposure has
      until recently received little attention. Lead exposure in early life can affect
      brain development with persisting influences on cognitive and behavioral
      functioning, as well as, elevated risks for developing a variety of diseases and
      disorders in later life. Although both sexes are affected by Pb exposure, the
      incidence, manifestation, and severity of outcomes appears to differ in males and
      females. Results from epidemiologic and animal studies indicate significant
      effect modification by sex, however, the results are not consistent across
      studies. Unfortunately, only a limited number of human epidemiological studies
      have included both sexes in independent outcome analyses limiting our ability to
      draw definitive conclusions regarding sex-differentiated outcomes. Additionally,
      due to various methodological differences across studies, there is still not a
      good mechanistic understanding of the molecular effects of lead on the brain and
      the factors that influence differential responses to Pb based on sex. In this
      review, focused on prenatal and postnatal Pb exposures in humans and animal
      models, we discuss current literature supporting sex differences in outcomes in
      response to Pb exposure and explore some of the ideas regarding potential
      molecular mechanisms that may contribute to sex-related differences in outcomes
      from developmental Pb exposure. The sex-dependent variability in outcomes from
      developmental Pb exposure may arise from a combination of complex factors,
      including, but not limited to, intrinsic sex-specific molecular/genetic
      mechanisms and external risk factors including sex-specific responses to
      environmental stressors which may act through shared epigenetic pathways to
      influence the genome and behavioral output.

PMID- 29662504
TI  - Comparison of the safety and efficacy of two types of drug-eluting balloons
      (RESTORE DEB and SeQuent(r) Please) in the treatment of coronary in-stent
      restenosis: study protocol for a randomized controlled trial (RESTORE ISR China).

PMID- 29662505
TI  - Comparison of in-hospital outcomes between octogenarians and nonagenarians
      undergoing transcatheter aortic valve replacement: a propensity matched analysis.
AB  - Background: Aortic valve stenosis (AS) is very common in the elderly patients
      above 80 years. Transcatheter aortic valve replacement (TAVR) in such patients is
      being increasingly performed. This study sought to assess in-hospital outcome
      differences between octogenarians and nonagenarians and predictors of mortality
      in nonagenarians undergoing TAVR with severe AS. Method: The study population was
      derived from the National Inpatient Sample (NIS) for the years 2012-2014 using
      ICD-9 CM procedure codes 35.05 and 35.06 for TAVR. Hospitalizations below 80
      years of age were excluded. After performing propensity score matching (1: 2), in
      hospital outcomes were compared in matched cohorts. Then, multivariate model was
      developed to analyze predictors of in-hospital mortality in nonagenarians.
      Results: There were 11,630 hospitalizations in the octogenarian and 5815
      hospitalizations in the nonagenarian group. Primary outcome of in-hospital
      mortality (6% vs. 4.1%, P <= 0.001) was higher in nonagenarians compared to
      octogenarians. Secondary outcomes including stroke (3.4% vs. 2.8%, P <= 0.001),
      renal failure (18.9% vs. 17.3%, P <= 0.001), blood transfusion (35% vs. 32.6%, P
      <= 0.001), vascular complications (4.5% vs. 3.5%, P <= 0.001), and pacemaker
      implantation (27.8% vs. 24.8%, P <= 0.001) were higher in nonagenarians. There
      was no difference in their length of stay. Median cost (70,374$ vs. 65,381$, P <=
      0.001) was slightly higher with nonagenarian. Conclusions: Although in-hospital
      mortality is slightly higher in nonagenarians, it is acceptable. This difference
      in mortality is at least partly explained by higher complications in
      nonagenarians. Efforts should be made to decrease the complications which can
      further narrow the difference in in-hospital mortality between the groups.

PMID- 29662506
TI  - Patterns of in-hospital mortality and bleeding complications following PCI for
      very elderly patients: insights from the Dartmouth Dynamic Registry.
AB  - Background: Very elderly patients (age >= 85 years) are a rapidly increasing
      segment of the population. As a group, they experience high rates of in-hospital
      mortality and bleeding complications following percutaneous coronary intervention
      (PCI). However, the relationship between bleeding and mortality in the very
      elderly is unknown. Methods: Retrospective review was performed on 17,378
      consecutive PCI procedures from 2000 to 2015 at Dartmouth-Hitchcock Medical
      Center. Incidence of bleeding during the index PCI admission (bleeding requiring
      transfusion, access site hematoma > 5 cm, pseudoaneurysm, and retroperitoneal
      bleed) and in-hospital mortality were reported for four age groups (< 65 years,
      65-74 years, 75-84 years, and >= 85 years). The mortality of patients who
      suffered bleeding complications and those who did not was calculated and
      multivariate analysis was performed for in-hospital mortality. Lastly, known
      predictors of bleeding were compared between patients age < 85 years and age >=
      85 years. Results: Of 17,378 patients studied, 1019 (5.9%) experienced bleeding
      and 369 (2.1%) died in-hospital following PCI. Incidence of bleeding and in
      hospital mortality increased monotonically with increasing age (mortality: 0.94%,
      2.27%, 4.24% and 4.58%; bleeding: 3.96%, 6.62%, 10.68% and 13.99% for ages < 65,
      65-74, 75-84 and >= 85 years, respectively). On multivariate analysis, bleeding
      was associated with increased mortality for all age groups except patients age >=
      85 years [odds ratio (95% CI): age < 65 years, 3.65 (1.99-6.74); age 65-74 years,
      2.83 (1.62-4.94); age 75-84 years, 3.86 (2.56-5.82), age >= 85 years: 1.39 (0.49
      3.95)]. Conclusions: Bleeding and mortality following PCI increase with
      increasing age. For the very elderly, despite high rates of bleeding, bleeding is
      no longer predictive of in-hospital mortality following PCI.

PMID- 29662507
TI  - New predictors of in-stent restenosis in patients with diabetes mellitus
      undergoing percutaneous coronary intervention with drug-eluting stent.
AB  - Background: Percutaneous coronary intervention (PCI) had become the major
      therapeutic procedure for coronary artery disease (CAD), but the high rate of in
      stent restenosis (ISR) still remained an unsolved clinical problem in clinical
      practice. Increasing evidences suggested that diabetes mellitus (DM) was a major
      risk factor for ISR, but the risk predictors of ISR in CAD patients with DM had
      not been well characterized. The aim of this study was to investigate the
      clinical and angiographic characteristic predictors significantly associated with
      the occurrence of ISR in diabetic patients following coronary stenting with drug
      eluting stent (DES). Methods: A total of 920 patients with diabetes who diagnosed
      CAD and underwent coronary DES implantation at Beijing Anzhen Hospital in China
      were consecutively enrolled from January 2012 to December 2012. Of these, 440
      patients underwent the second angiography within >= 6 months due to the
      progression of treated target lesions. Finally, 368 of these patients who met the
      inclusion and exclusion criteria were followed up by angiography after baseline
      PCI. According to whether ISR was detected at follow-up angiography, patients
      were divided into the ISR group (n = 74) and the non-ISR group (n = 294). The
      independent predictors of ISR in patients with DM were explored by multivariate
      Cox's proportional hazards regression models. Results: A total of 368 patients
      (260 women and 108 men) with a mean ages of 58.71 +/- 10.25 years were finally
      enrolled in this study. Of these, ISR occurred in 74/368 diabetic patients
      (20.11%) by follow-up angiography. Univariate analysis showed that most baseline
      characteristics of the ISR and non-ISR group were similar. Patients in the ISR
      group had significantly higher serum very low density lipoprotein cholesterol
      (VLDL-C), triglyceride (TG) and uric acid (UA) levels, more numbers of target
      vessel lesions, higher prevalence of multi-vessel disease, higher SYNTAX score,
      higher rate of previous but lower rate of drinking compared with patients in the
      non-ISR group. The independent predictors of ISR in patients with DM after DES
      implantation included VLDL-C (HR = 1.85, 95% CI: 1.24-2.77, P = 0.002), UA (per
      50 umol/L increments, HR = 1.19, 95% CI: 1.05-1.34, P = 0.006), SYNTAX score (per
      5 increments, HR = 1.34, 95% CI: 1.03-1.74, P = 0.031) and the history of PCI (HR
      = 3.43, 95% CI: 1.57-7.80, P = 0.003) by the multivariate Cox's proportional
      hazards regression analysis. Conclusions: The increased serum VLDL-C and UA
      level, higher SYNTAX score and the history of previous PCI were independent
      predictors of ISR in patients with DM after coronary DES implantation. It
      provided new evidence for physicians to take measures to lower the risk of ISR
      for the better management of diabetic patients after PCI.

PMID- 29662508
TI  - Obstructive sleep apnea is associated with severity and long-term prognosis of
      acute coronary syndrome.
AB  - Background: Obstructive sleep apnea (OSA) is a common disease in patients with
      acute coronary syndrome (ACS) and associated with an increased risk of fatal and
      nonfatal cardiovascular events. However, most patients in previous study were
      treated with bare metal stents and the sample sizes were relatively low. The goal
      of this study was to evaluate the influence of OSA on the severity and prognosis
      of patients admitted for ACS. Methods: In this prospective cohort study, we
      enrolled patients with ACS who were hospitalized for coronary
      angiogram/percutaneous coronary intervention and undergone polysomnography. We
      divided the patients into two groups: moderate to severe OSA group [apnea
      hypopnea index (AHI) > 15 events/h] and control group (AHI <= 15 events/h). They
      were followed up for up 32 months. Then, we compared the ACS severity and long
      term major adverse cardiovascular events (MACE) in patients with different
      severity of OSA. Results: Five hundred and twenty nine patients were included in
      the final analysis, with 76% of them being men and an average age of 59 +/- 10
      years. The overall mean AHI is 29 +/- 19 events/h, 70.5% of them (373/529) being
      with moderate to severe OSA and 29.5% (156/529) assign into control group.
      Compared with controls, patients with moderate or severe OSA exhibited a higher
      prevalence of hypertension as well as higher body mass index, SYNTAX score,
      Epworth score and length of hospitalization. With a median follow-up duration of
      30 months, accumulative rate of MACE was also higher in patients with moderate or
      severe OSA than that in the control group (8.6% vs. 3.2%, P = 0.028). After
      adjusting for baseline confounders by cox regression model, moderate to severe
      OSA was an independent risk factor of long-term MACE (P = 0.047, HR = 1.618, 95%
      CI: 1.069-3.869). Conclusions: The results of this study demonstrate that
      moderate or severe OSA is correlated with disease severity and associated with
      worse long-term prognosis in ACS patients. The results raising the possibility
      that early diagnose and interventions of OSA could improve long-term outcomes in
      ACS patients.

PMID- 29662509
TI  - Adherence to pharmacological and non-pharmacological treatment of frail
      hypertensive patients.
AB  - Objective: To investigate the relationship between frailty syndrome (FS) and
      adherence to pharmacological and non-pharmacological treatment for hypertension.
      Methods: The study included 100 patients diagnosed with hypertension and treated
      with one or more hypotensive drugs. Results: Frail patients obtained low scores
      (4.1 +/- 2.0) for adherence to pharmaceutical treatment of hypertension, while
      non-frail patients obtained moderate scores (6.1 +/- 2.1). Non-frail patients had
      higher scores in two out of four domains of the Health Behavior Inventory (HBI):
      positive mental attitudes (3.6 +/- 0.4 vs. 3.2 +/- 0.5; P = 0.006) and health
      practices (3.6 +/- 0.5 vs. 3.2 +/- 0.5; P < 0.03); as well as higher global
      scores (HBI raw score): 83.3 +/- 10.6 vs. 77.3 +/- 9.5; P < 0.03. Multiple
      regression analysis showed that frailty syndrome (FS) was a statistically
      significant independent determinant of worse adherence to pharmacological
      treatment (beta = -0.27; P < 0.001) and health behaviors (beta = -0.10; P =
      0.036). Education was a statistically significant independent determinant of
      better adherence to pharmacological treatment (beta = 0.82; P = 0.012), while net
      income positively affected health behaviors as measured by the HBI (beta = 0.39;
      P = 0.046). Conclusions: FS is a significant independent factor contributing to
      worse adherence to pharmacological and non-pharmacological treatment of
      hypertension. Better education significantly improves patients' adherence to the
      prescribed pharmacological treatment, while a good financial standing evidenced
      by high net income is a determinant of better adherence to health-related
      behaviors recommended in hypertension treatment.

PMID- 29662510
TI  - Long term outcomes of drug-eluting stent versus coronary artery bypass grafting
      for left main coronary artery disease: a meta-analysis.
AB  - Background: It is still controversial whether percutaneous coronary intervention
      with drug-eluting stent (DES) is safe and effective compared to coronary artery
      bypass graft surgery (CABG) for unprotected left main coronary artery (ULMCA)
      disease at long-term follow up (>= 3 years). Methods: Eligible studies were
      selected by searching PubMed, EMBASE, and Cochrane Library up to December 6,
      2016. The primary endpoint was a composite of death, myocardial infarction (MI)
      or stroke during the longest follow-up. Death, cardiac death, MI, stroke and
      repeat revascularization were the secondary outcomes. Results: Four randomized
      controlled trials and twelve adjusted observational studies involving 14,130
      patients were included. DES was comparable to CABG regarding the occurrence of
      the primary endpoint (HR = 0.94, 95% CI: 0.86-1.03). Besides, DES was
      significantly associated with higher incidence of MI (HR = 1.56, 95% CI: 1.09
      2.22) and repeat revascularization (HR = 3.09, 95% CI: 2.33-4.10) compared with
      CABG, while no difference was found between the two strategies regard as the rate
      of death, cardiac death and stroke. Furthermore, DES can reduce the risk of the
      composite endpoint of death, MI or stroke (HR = 0.80, 95% CI: 0.67-0.95) for
      ULMCA lesions with SYNTAX score <= 32. Conclusions: Although with higher risk of
      repeat revascularization, PCI with DES appears to be as safe as CABG for ULMCA
      disease at long-term follow up. In addition, treatment with DES could be an
      alternative interventional strategy to CABG for ULMCA lesions with low to
      intermediate anatomic complexity.

PMID- 29662511
TI  - Treatment of coronary in-stent restenosis: a systematic review.
AB  - Coronary stent implantation has significantly improved percutaneous coronary
      intervention and enabled the management of early complications of plain balloon
      angioplasty. However, a new complication has accompanied these improvements: in
      stent restenosis (ISR) arising from neointimal hyperplasia. ISR after coronary
      angioplasty is currently one of the main limitations of this method, leading to
      the recurrence of exertional angina pectoris or acute coronary syndromes. The
      clinical incidence of ISR after bare-metal stent (BMS) implantation is
      approximately 20%-35%. The use of drug-eluting stents (DES) has led to a further
      decrease in the occurrence of ISR to 5%-10%. Evidence resulting from controlled
      clinical studies suggests that DES and drug-eluting balloon catheters (DEB)
      provide the best clinical and angiographic results in the treatment of ISR. We
      undertook a systematic review of the pathophysiology, diagnostics and treatment
      options for BMS- and DES-ISR. We discuss recent randomised studies, comparing
      different DES or DEB used for BMS or DES-ISR treatment, as well as the use of new
      biovascular scafolds and the topic of scafold restenosis.

PMID- 29662513
TI  - Repetitive narrow QRS tachycardia in a 61-year-old female patient with recent
      palpitations.

PMID- 29662512
TI  - Prediction of sudden death in elderly patients with heart failure.
AB  - Most heart failure (HF) related mortality is due to sudden cardiac death (SCD)
      and worsening HF, particularly in the case of reduced ejection fraction.
      Predicting and preventing SCD is an important goal but most works include no or
      few patients with advanced age, and the prevention of SCD in elderly patients
      with HF is still controversial. A recent reduction in the annual rate of SCD has
      been recently described but it is not clear if this is also true in advanced age
      patients. Age is associated with SCD, although physicians frequently have the
      perception that elderly patients with HF die mainly of pump failure,
      underestimating the importance of SCD. Other clinical variables that have been
      associated to SCD are symptoms, New York Heart Association functional class,
      ischemic cause, and comorbidities (chronic obstructive pulmonary disease, renal
      dysfunction and diabetes). Some test results that should also be considered are
      left ventricular ejection fraction and diameters, natriuretic peptides, non
      sustained ventricular tachycardias and autonomic abnormalities. The combination
      of all these markers is probably the best option to predict SCD. Different risk
      scores have been described and, although there are no specific ones for elderly
      populations, most include age as a risk predictor and some were developed in
      populations with mean age > 65 years. Finally, it is important to stress that
      these scores should be able to predict any type of SCD as, although most are due
      to tachyarrhythmias, bradyarrhythmias also play a role, particularly in the case
      of the elderly.

PMID- 29662514
TI  - Intravascular ultrasound guided retrograde guidewire true lumen tracking
      technique for chronic total occlusion intervention.

PMID- 29662515
TI  - Thyrotoxicosis induced cardiogenic shock rescued by extracorporeal membrane
      oxygenation.

PMID- 29662517
TI  - Measuring Children's Mental Health Outcomes from a Service Perspective.

PMID- 29662516
TI  - Adolescent and Young Adult Testicular Germ Cell Tumors: Special Considerations.
AB  - While testicular germ cell tumors (T-GCTs) make up only 0.5% of pediatric
      malignancies and less than 2% of adult malignancies, they comprise 14% of
      adolescent malignancies, making it the most common solid tumor in this age group.
      The transition in incidence at this age is also accompanied by a transition in
      tumor histology with adolescents having mostly pure embryonal carcinoma and mixed
      nonseminomatous germ cell tumors. Similar to T-GCTs of all ages, surgical
      excision with orchiectomy is the standard initial step in treatment.
      Chemotherapy, retroperitoneal lymph node dissection, and targeted treatment of
      distant metastases make even widely disseminated disease treatable and curable.
      For this reason, in many ways, the future focus has expanded beyond survival
      alone to emphasize quality of life issues such as fertility and hypogonadism.
      However, adolescents remain the age group least studied or understood as they
      fall in between the ages included in most study designs. Also, they require the
      most psychosocial support because of the challenges unique to the adolescent
      period. In this review, we aim to highlight the known outcome data for T-GCTs in
      this population and also to discuss the unique aspects of treatment and support
      for this age group.

PMID- 29662518
TI  - Letter To The Editor.

PMID- 29662519
TI  - Response to "A critique for the new Canadian FASD diagnostic Guidelines".

PMID- 29662520
TI  - Measuring Children's Mental Health in Ontario: Policy Issues and Prospects for
      Change.
AB  - Children's mental health in Canada is characterized by high needs coupled with
      stark service shortfalls. In Ontario and in many provinces, addressing these
      shortfalls is hampered by the absence of a measurement system, something that
      researchers have long called for. This commentary aims to review the issues and
      suggest prospects for improving the measurement of children's mental health in
      Ontario and elsewhere. As background, we first describe the children's mental
      health needs; outline the rationale for a measurement system; describe previous
      attempts to introduce such systems, including in Ontario; and discuss the current
      Ontario situation. We then explore some of the issues that constrain policy and
      that need to be overcome, and suggest prospects for change - for advancing the
      measurement of children's mental health in Ontario and Canada.

PMID- 29662521
TI  - Evaluating Training Programs for Primary Care Providers in Child/Adolescent
      Mental Health in Canada: A Systematic Review.
AB  - Introduction: The need for child/adolescent mental health care in Canada is
      growing. Primary care can play a key role in filling this gap, yet most providers
      feel they do not have adequate training. This paper reviews the Canadian
      literature on capacity building programs in child and adolescent psychiatry for
      primary care providers, to examine how these programs are being implemented and
      evaluated to contribute to evidence-based initiatives. Methods: A systematic
      literature review of peer-reviewed published articles of capacity building
      initiatives in child/adolescent mental health care for primary care practitioners
      that have been implemented in Canada. Results: Sixteen articles were identified
      that met inclusion criteria. Analysis revealed that capacity building initiatives
      in Canada are varied but rigorous evaluation methodology is lacking. Primary care
      providers welcome efforts to increase mental health care capacity and were
      satisfied with the implementation of most programs. Discussion: Objective
      conclusions regarding the effectiveness of these programs to increase mental
      health care capacity is challenging given the evaluation methodology of these
      studies. Conclusion: Rigorous evaluation methods are needed to make evidence
      based decisions on ways forward to be able to build child/adolescent mental
      health care capacity in primary care. Outcome measures need to move beyond self
      report to more objective measures, and should expand the measurement of patient
      outcomes to ensure that these initiative are indeed leading to improved care for
      families.

PMID- 29662522
TI  - Regional Variations in Suicide and Undetermined Death Rates among Adolescents
      across Canada.
AB  - Objective: Trends in rates of adolescent suicide and undetermined deaths in
      Canada from 1981 to 2012 were examined, focusing specifically on variations
      between Canadian regions. Exploratory hypotheses were formulated for regional
      variability in adolescent suicide rates over time in Canada. Methods: A
      descriptive time trend analysis using public domain vital statistics data was
      performed. All deaths from 1981 to 2012 among 15 to 19 year olds coded as
      suicides or undetermined intent according to the International Classification of
      Diseases, 9th and 10th Revisions were included. Results: While there was an
      overall stability in adolescent suicide and undetermined death rates across
      Canada, regional analyses showed that Quebec experienced a 7.6% annual reduction
      between 2001 and 2012 while the Prairies and Atlantic provinces experienced
      significant annual increases since 2001. Ontario and British Columbia have had
      non-significant fluctuations since 2001. The trends remained similar overall when
      excluding undetermined deaths from the analyses. Conclusions: Variations in
      adolescent suicide trends across provinces were found. Factors such as provincial
      suicide action and prevention legislation contributing to these variations remain
      to be studied, but these regional differences point towards the need for better
      consistency of suicide prevention strategies across the country.

PMID- 29662523
TI  - Sexual Health of Adolescent Patients Admitted to a Psychiatric Unit.
AB  - Objective: To review sexual health screening practices during admission to an
      adolescent psychiatry unit. Method: Retrospective chart review of randomly
      selected youth admitted over a one-year period (2013). Data extracted included
      demographics, reasons for admission, sexual health history, as well as any
      comorbid behaviours noted. The main outcome measure was whether sexual health
      details were documented at any time during admission; if so, this information was
      extracted for analysis. Statistical analysis was done using univariate
      associations and logistic association. Results: Mean age of subjects (n=99, 79
      females and 20 males) was 15.24 years (SD = 1.30). Most common reasons for
      admission were suicidal gestures/self harm (n=57, 58%) and mood disorders (n=53,
      54%). Thirty-seven patients (37%) had sexual health information documented in
      their charts. No demographic variables were significantly associated with being
      asked sexual health questions. Patients who had mood disorder diagnoses had 6
      times the odds (95%CI: 1.18 to 29.96, P=0.03) of sexual health questions being
      documented compared to those not diagnosed with mood disorders. Conclusions:
      Screening for sexual health concerns is not being documented in the majority of
      adolescent psychiatry inpatients. Omitting sexual health screening during
      hospitalizations represents a missed opportunity for investigation and management
      of sexual health issues in this high-risk group. As many adolescents, particular
      those struggling with mental illness, do not attend preventative health visits,
      screening for pregnancy risk and other reproductive health needs is recommended
      at every adolescent encounter and in all settings.

PMID- 29662524
TI  - Parent-only Group Cognitive Behavioral Intervention for Children with Anxiety
      Disorders: A Control Group Study.
AB  - Objective: Parents play an important role in development and continuation of
      anxiety disorders in children. Yet the evidence on parent contribution in
      cognitive behavioral therapy (CBT) for childhood anxiety is limited. This open
      randomized trial examined the effectiveness of a parent-directed group CBT to
      manage children with anxiety disorders. Method: Parents of 42 children aged 6-12
      with primary anxiety disorders were allocated to a six, two-hour weekly
      intervention and a wait-list (WL) control. The Revised Children's Manifest
      Anxiety, Children's Depression Inventory, Strengths and Difficulties
      Questionnaire-Home Version, Depression-Anxiety-Stress Scale, Children Global
      Assessment Scale, and Global Relational Assessment of Functioning were used to
      assess children's and parents' functioning and emotional symptoms. Parents
      completed consumer satisfaction questionnaire. Results: Parents in the CBT group
      reported significant improvement in their depressive symptoms (p=0.006) and the
      family functioning (p=0.04), as well as reduction in children's emotional
      symptoms (p=0.007). Clinician rating of children's functioning showed significant
      improvement in the CBT group(p=0.001). There was no significant difference in
      children rating of their anxiety within groups from pre- to post-intervention.
      Parents were satisfied mostly with the intervention. Conclusion: A brief parent
      only CBT based intervention can be effective in the management of childhood
      anxiety.

PMID- 29662525
TI  - Video-conferencing Telehealth Linkage attempts to Schools to Facilitate Mental
      Health Consultation.
AB  - Objective: Telehealth to schools may be a strategic approach to expand child
      mental health service delivery, however, there are only a few published examples.
      This report describes video-conferencing telehealth linkage attempts to schools
      to facilitate mental health consultation. Methods: A series of synchronous video
      conferencing linkage strategies were attempted to connect a mental health
      consultation service to multiple schools in a Canadian setting. Consultation to
      support the implementation of the Daily Report Card, for students with
      attentional and behavioural problems, was the core content of this pilot linkage
      attempt. Results: Synchronous video conference consultations were successfully
      delivered to six elementary schools across three school districts. Two of three
      linkage strategies were functional. One used existing health centre-based
      telehealth units to connect to school-based dedicated tablets with a video
      collaboration app and reliance on existing school Wi-Fi. A second used existing
      laptops in both the health and school system linked through a communication
      platform. A third connection, using 3G/4G hotspots to obviate the need to access
      school Wi-Fi, was deemed too expensive in this setting. Conclusion: The potential
      to use existing computer hardware to connect mental health providers and schools
      could facilitate scale-up. However, it is unknown whether mental health systems
      and school sectors will invest in such linkages and reorganize core mental health
      services to be delivered in this way.

PMID- 29662526
TI  - Factors Predicting Length of Stay in an Adolescent Psychiatric Unit, South Bronx,
      NY: A Short Report.
AB  - Objective: Mental health disorders account for around 1.8 million inpatient
      community hospital stays in the U.S.A. Our study aims to highlight the factors
      impacting the length of stay at a community hospital in the U.S.A. Methods: We
      reviewed 300 randomly selected charts to examine the factors impacting the length
      of stay in an adolescent inpatient psychiatric unit in 2011 and 2015. All data
      were analyzed in SPSS v. 20 with multiple regression analysis. Results: Longer
      length of stay among adolescents was associated with multiple psychiatric
      diagnoses, co-occurring medical comorbidities, not living with biological
      parents, history of mental illness, legal problems, substance use in the family,
      seclusion, restraints during current admission, and schizophrenia. Conclusion:
      Longer length of stay among adolescents in a psychiatric inpatient unit was
      associated with severity of psychopathology, hospital parameters and family
      stability.

PMID- 29662527
TI  - Stimulant Withdrawal in a Child with Autism Spectrum Disorder and ADHD - A Case
      Report.
AB  - Objective: To consider whether the concepts of tolerance and withdrawal to
      stimulant medications apply to a preadolescent female, affected by autism
      spectrum disorder (ASD) and treated for associated attention
      deficit/hyperactivity disorder (ADHD). Methods: We describe the case history and
      review scientific English language literature pertaining to acute withdrawal
      effects associated with methylphenidate and amphetamine derivatives in children.
      Results: An 11-year-old female with ASD and ADHD referred to our clinic
      experienced vomiting, headaches, and light sensitivity following abrupt
      discontinuation of methylphenidate; she subsequently presented with migraines and
      marked malaise immediately after a dose reduction in lisdexamfetamine. Evidence
      supports the notion that ADHD symptoms in children with ASD can be effectively
      treated with methylphenidate; however, beneficial effects are less robust
      relative to children with a primary ADHD diagnosis. Children affected by ASD are
      also more susceptible to adverse effects. Literature on withdrawal from
      stimulants in children is limited to case studies; in contrast, in the adult
      population more information is available, especially in adults with substance
      abuse disorders. Adults experiencing stimulant withdrawal often experience
      depression, fatigue, changes in appetite, and insomnia or hypersomnia.
      Conclusions: We argue that tolerance to stimulants was conceivably developing in
      this young female, and consequently discontinuation of methylphenidate and dose
      reduction of lisdexamfetamine resulted in withdrawal symptoms. Children with ASD
      are more sensitive to stimulant medications and we wonder whether this extends to
      an increased sensitivity to developing tolerance to stimulant medication.
      Clinicians ought to be vigilant about the emergence of symptomology suggestive of
      withdrawal phenomena following stimulant discontinuation.

PMID- 29662528
TI  - Oncoplastic surgery for the conservative treatment of breast cancer in Peru's
      National Cancer Institute.
AB  - Background: Oncoplastic surgery for breast cancer (OPS) has been a surgical trend
      for the past 25 years. In 2012, OPS has been introduced as the standard treatment
      for a selected group of patients at the National Cancer Institute of Peru (INEN).
      The aim of this study is to describe our findings. Methods: This is a
      retrospective and descriptive study that identified demographics, tumour
      pathologic features and includes patients solely treated since diagnosis until
      late follow-up at INEN. These OPS patients were identified from the conservative
      treatment patients group by review of medical charts and creation of a database
      for periods December 2005 through December 2015. Results: A total of 146 patients
      were ruled in by the inclusion criteria. All patients were Peruvian females,
      56.2% being 51 or older. 93.8% had core biopsy diagnosis of breast cancer and
      52.1% located at the upper outer quadrant. 79.5% patients had upfront OPS and the
      round block (43.2%) and reduction/mastopexy (23.3%) were the most used
      techniques. pT2 was the most frequent size (54.7%). We achieved negative margins
      in 134 patients (93.2%) in a single procedure. Of 29 patients, who had
      neoadjuvant treatment, 11 achieved pCR. Only 5.5% had pN2 or higher. 95.2%
      received complimentary external beam radiotherapy. Conclusions: OPS has proven to
      be a reliable surgical option, both for aesthetic and oncologic outcomes.
      Important points for achieving these results are breast surgeons having properly
      trained under the OPS philosophy and knowing the patients' characteristics for
      correct technique selection.

PMID- 29662529
TI  - Neoadjuvant chemotherapy in locally advanced duodenal adenocarcinoma.
AB  - Duodenal adenocarcinoma (ADC) represents only 0.3% of gastrointestinal neoplasms.
      With the frequency being higher between the ages of 40 and 60, it is
      predominantly located in the second part of the duodenum and around the
      periampullary region. Symptoms are nonspecific, so the majority of patients
      present with advanced disease. Neoadjuvant chemotherapy is a therapeutic option
      that has not been well studied. The global literature includes only isolated
      reports on this subject. This is why we are presenting the following case: a 60
      year-old female patient with a locally advanced, inoperable duodenal ADC received
      neoadjuvant chemotherapy. Having presented a favourable response as observed in
      the post-neoadjuvant extension studies, a pancreaticoduodenectomy was performed
      without any perioperative complications and with satisfactory progress. The final
      biopsy reported a complete pathological response. After being monitored for 34
      months, the patient was free from locoregional and distant metastatic disease.
      During the last weeks of monitoring, she developed a second primary breast
      tumour, which has been corroborated by immunohistochemistry.

PMID- 29662530
TI  - Are we ready for routine precision medicine? Highlights from the Milan Summit on
      Precision Medicine, Milan, Italy, 8-9 February 2018.
AB  - On 8 and 9 February 2018, the IFOM-IEO campus in Milan hosted the Milan summit on
      Precision Medicine, which gathered clinical and translational research experts
      from academia, industry and regulatory bodies to discuss the state of the art of
      precision medicine in Europe. The meeting was pervaded by a generalised feeling
      of excitement for a field that is perceived to be technologically mature for the
      transition into clinical routine but still hampered by numerous obstacles of a
      methodological, ethical, regulatory and possibly cultural nature. Through lively
      discussions, the attendees tried to identify realistic ways to implement a
      technology-rich precision approach to cancer patients.

PMID- 29662531
TI  - Cystic brain metastases in ALK-rearranged non-small cell lung cancer.
AB  - The central nervous system (CNS) is a common site of disease progression in
      patients with non-small-cell lung cancer (NSCLC) with anaplastic lymphoma kinase
      (ALK)-rearrangement treated with crizotinib. Cystic brain metastases (CBM) have
      been recently identified as one possible variant of this disease. An illustrative
      case report is presented along with a literature review performed in order to
      track relevant papers about CBM in ALK-rearranged NSCLC, including possible
      pathophysiology, differential diagnosis and treatment options for this condition.
      Three case reports have been published describing six ALK-rearranged NSCLC
      patients presenting with CBM, all of which were under treatment with crizotinib
      by the time of CBM diagnosis. Treatment with CNS-penetrating tyrosine kinase
      inhibitors (TKIs) resulted in CNS disease control in three of the six cases
      reported either as single therapy or in combination with radiation therapy (RT).
      Investigation of differential diagnoses of CBM might be necessary, which include
      inflammatory and demyelinating disorders, primary brain tumours and infectious
      diseases, especially neurocysticercosis that might mimic CBM images. Treatment
      options include RT, CNS-penetrating TKIs and invasive procedures, such as
      stereotactic drainage. Thus, CBM are associated with ALK-rearranged NSCLC,
      particularly in patients who use crizotinib and should prompt investigation of
      differential diagnosis. CNS-penetrating TKIs are effective in the control of
      solid brain metastases and also seem to be active in CBM as single therapy or in
      combination with RT.

PMID- 29662532
TI  - Cosmesis after early stage breast cancer treatment with surgery and radiation
      therapy: experience of patients treated in a Chilean radiotherapy centre.
AB  - Aim: To analyse the overall cosmetic outcome according to patient self-assessment
      in relation to the fractionation received. Materials and methods: A
      questionnaire, drawn up on the basis of subjective rating scales of cosmesis and
      of acute and late toxicity RTOG/EORTC, EORTC QLQ-C30 (v3) and LENT SOMA, was
      applied to patients with early-stage breast cancer who received radiotherapy with
      tangential fields between June 2014 and July 2015. Self-perception of cosmesis,
      changes in the treated breast, pain and fractionation used (hypofractionation
      (HF) 42.56 Gy in 16 fractions or conventional fractionation (CF) 50 Gy in 25
      fractions) were evaluated. Results: Three hundred and fifty-two questionnaires
      were obtained. The median age was 58 years. 45% of patients reported 'excellent'
      cosmesis, 53% 'good', and 2% 'poor' cosmesis. Cosmesis was considered
      'excellent/good' by 98% of patients. No statistically significant difference was
      found in overall cosmesis according to fractionation received (p = 0.6).The most
      frequent alteration was 'difference between both breasts' (77%), and 48% reported
      change in normal breast colour.Fifteen percent of patients who are younger than
      58 years reported a change of normal breast colour affecting cosmesis compared to
      9% of patients older than 58 years (p = 0.04).Complications affecting breast
      cosmesis were reported by 9% of patients with stages I-II compared with 2% with
      cancer in situ (DCIS) (p = 0.04); 14% in stages I-II referred colour change
      affecting cosmesis compared to 6% of those with DCIS (p = 0.03).Ninety-four
      percent of patients stated that they would accept treatment again. Conclusions:
      No difference in cosmetic results was found between HF and CF in our patients.
      Great satisfaction regarding cosmetic outcome of cancer treatment was reported,
      given by 98% of excellent/good cosmesis, and 94% of patients who would receive
      treatment again.

PMID- 29662533
TI  - Highlights from the 10th Breast, Gynaecological and Immunotherapy International
      Cancer Conference (BGICC), 18-19 January 2018, Cairo, Egypt.
AB  - During the 10th Breast, Gynaecological and Immunotherapy International Cancer
      Conference (BGICC), which was held on 18 and 19 of January, 2018, in Cairo,
      Egypt, around 100 international, regional and national experts presented the
      latest updates in breast cancer, gynaecological cancers and immunotherapy in
      oncology. Through this report, we will try to highlight the important data and
      consensus issues that were discussed during the conference.

PMID- 29662534
TI  - Obesity and outcome of post-menopausal women receiving adjuvant letrozole for
      breast cancer.
AB  - Introduction: Aromatase enzyme activity is predominant in adipose tissue. This
      has led to speculation that aromatase activity is elevated in obese women and
      subsequently decreased the clinical activity of adjuvant aromatase inhibitors
      (AIs) in women with estrogen receptor positive (ER+) breast cancer (BC). We
      investigated the effect of obesity on the outcome of this population. Patients
      and methods: Records of 320 consecutive post-menopausal (PM) women with ER+ BC
      starting single agent adjuvant letrozole between years 2005 and 2014 were
      retrospectively reviewed. Tumour and patients characteristic including body mass
      index (BMI) on the day of starting letrozole were extracted. Endpoints of main
      interest were: (1) Frequency of obesity; (2) relapse-free survival (RFS) in
      nonobese (G1; BMI < 30) and obese (G2; BMI >= 30) patients. Results: Obesity
      (BMI: 30-34.99) and morbid obesity (BMI >= 35) were present in 105/320 (32.8%)
      and 115/320 (35.9%) women, respectively. Median follow-up of patients was 49
      months; RFS at 5 years (G1: 69% versus G2: 78%) and at 8 years (G1: 69% versus
      G2: 71%). Median RFS is not reached in both groups (Log rank; P = 0.097). There
      was no correlation between BMI and RFS (correlation coefficient r = 0.075; P =
      0.174). Conclusion: In this cohort, more than two-thirds of PM women starting
      adjuvant AIs are obese. Obesity did not adversely affect the outcome of women on
      adjuvant letrozole.

PMID- 29662536
TI  - Attrition as one of the challenges of developing a palliative care centre:
      experience of the Indian Institute of Head and Neck Oncology, Indore, India.
AB  - Palliative care is an essential component of health care delivery. With respect
      to India, currently, despite rapid socio economic development, there are
      tremendous challenges in offering institutional palliative care due to several
      factors. A major factor has been an acute shortage of trained palliative care
      professionals. Another has been the fact that the majority of India's population
      is not covered by any health insurance. We describe the problems, including
      attrition faced by the Indian Institute of Head and Neck Oncology, in the central
      Indian state of Madhya Pradesh.

PMID- 29662535
TI  - Adipose tissue stem cells in regenerative medicine.
AB  - Adipose tissue-derived stem cells (ADSCs) are mesenchymal cells with the capacity
      for self-renewal and multipotential differentiation. This multipotentiality
      allows them to become adipocytes, chondrocytes, myocytes, osteoblasts and
      neurocytes among other cell lineages. Stem cells and, in particular, adipose
      tissue-derived cells, play a key role in reconstructive or tissue engineering
      medicine as they have already proven effective in developing new treatments. The
      purpose of this work is to review the applications of ADSCs in various areas of
      regenerative medicine, as well as some of the risks associated with treatment
      with ADSCs in neoplastic disease.

PMID- 29662537
TI  - Untire: an all-embracing self-management eHealth program to cope with cancer
      related fatigue.
AB  - Cancer-related fatigue (CRF) is a frequent and invalidating problem in (former)
      cancer patients. If there are no medical causes, relief of fatigue can be
      attained by means of non-pharmacological interventions. Guidelines prescribe a
      multimodal approach with a focus on mental processes, physical activity and
      sleep. Online interventions have been shown to be effective in reducing CRF.
      These results inspired the creation of an all-embracing app on the various
      behavioural and physical activity modification themes that are recommended in
      oncological guidelines. This basis for the 'Untire' app is the Daily Program,
      consisting of 4 components. In 2018, the 'Untire' app will be launched in several
      languages throughout the European Union and some other countries outside Europe,
      such as the USA. Its effectiveness will be studied by means of a randomized
      controlled trial.

PMID- 29662538
TI  - The accuracy of intestinal ultrasound compared with small bowel capsule endoscopy
      in assessment of suspected Crohn's disease in patients with negative
      ileocolonoscopy.
AB  - Background: Small bowel involvement in Crohn's disease (CD) is frequently
      proximal to the ileocecal valve and inaccessible by conventional ileocolonoscopy
      (IC). Small bowel capsule endoscopy (SBCE) is among the prime modalities for
      assessment of small bowel disease in these patients. Intestinal ultrasound (IUS)
      is an accurate bedside fast and low-cost diagnostic modality utilized in CD for
      both diagnosis and monitoring. The aim of this study was to examine the accuracy
      of IUS in patients with suspected CD after a negative IC, and to evaluate the
      correlation of IUS with SBCE, inflammatory biomarkers and other cross-sectional
      imaging techniques. Methods: Prospective single center study in which patients
      with suspected CD underwent IUS and SBCE examinations within 3 days. IUS results
      were blindly compared with SBCE that served as the gold standard. A post hoc
      comparison was performed of IUS and SBCE results and available cross-sectional
      imaging results (computed tomography or magnetic resonance enterography) as well
      as inflammatory biomarkers if measured. The study cohort was followed for 1 year.
      In case of discordance between the IUS and SBCE results, the diagnosis at 1 year
      was reported. Results: Fifty patients were included in the study. The diagnostic
      yield of both IUS and SBCE for the diagnosis of small bowel CD was 38%. The IUS
      findings significantly correlated to small bowel inflammation detected by SBCE (r
      = 0.532, p < 0.001), with fair sensitivity and specificity (72% and 84%). Cross
      sectional imaging results significantly correlated to IUS as well (r = 0.46, p =
      0.018). Follow up was available in 8 of the 10 cases of discordance between IUS
      and SBCE. In all of these cases, diagnosis of CD was not fully established at the
      end of the follow up. Conclusions: The diagnostic yield of CE and IUS for
      detection of CD in patients with negative ileocolonoscopy was similar. IUS can be
      a useful diagnostic tool in suspected CD when IC is negative.

PMID- 29662539
TI  - Urogenital tuberculosis, the cause of ineffective antibacterial therapy for
      urinary tract infections.
AB  - Background: Urogenital tuberculosis (UGTB) is one of the great imitators; it is
      commonly masked by urinary tract infections (UTIs). We aimed to estimate how many
      UGTB patients were among patients with a long history of UTIs. Material and
      Methods: A total of 244 patients with recurrent UTIs and suspected UGTB were
      enrolled in an open, noncomparative prospective study. Their urine and expressed
      prostate secretion or ejaculate were cultured (a total of 1446 samples), and 421
      isolates with growth of ?104 colony-forming units (CFU)/ml were investigated for
      drug resistance. Typically, UGTB diagnosis is made by individual case. Results:
      All 244 patients had a long history of recurrent UTIs (on average, 7.9 +/- 3.4
      years); all received at least five courses of antibacterial therapy without good
      result. UGTB was diagnosed in 63 (25.8%), and in 41 of these (65.1%), there was
      comorbidity of UTI and UGTB. Of 1446 samples investigated, 421 (29.1%) were
      positive, and 1025 were negative. Escherichia coli was found in 57.3% of gram
      negative microflora and in 29.0% only among all uropathogens. E. coli was
      resistant to amoxicillin/clavulanate in 51.5-57.1%, to cefotaxime in 50.0-52.0%,
      to gentamycin in 33.3-59.5%, to ciprofloxacin in 63.2-66.7%, to levofloxacin in
      54.8-45.2%, and to nitrofurantoin in 23.5-20.8% in 2015 and 2016, respectively.
      If, in 2015, all isolates of E. coli were susceptible to imipenem, in 2016, 7.1%
      of strains were resistant to this antibiotic. Level of drug-resistance was higher
      in 2016, excluding only levofloxacin and nitrofurantoin. Conclusions: Total
      prevalence of UGTB among UTI patients with poor results of antibacterial therapy
      was 25.8%. Comorbidity of UTI and UGTB was diagnosed in 65.1%.

PMID- 29662540
TI  - The impact of comorbidities, sex and age on the occurrence of acute kidney injury
      among patients undergoing nephron-sparing surgery.
AB  - Background: The aim of this study was to report the impact of patients' baseline
      characteristics on the incidence of acute kidney injury (AKI) after nephron
      sparing surgery (NSS) for localized kidney cancer. Patients and methods: Data
      from our kidney cancer database were retrospectively extracted to include 402
      patients who underwent NSS between March 2000 and June 2016, and had sufficient
      data. Definition of AKI was based on the postoperative serum creatinine levels
      and estimated glomerular filtration rate (eGFR) magnitude, which were measured
      during the 72 h after surgery. Results: Based on RIFLE and AKIN criteria, the
      overall rate of postoperative AKI was 35%. The average decrease in eGFR among
      patients who developed AKI was 20% as compared with the non-AKI subgroup (2%). In
      univariate analysis, variables that were associated with AKI included right-sided
      tumors (p = 0.014), male sex (p = 0.01), hypertension (p = 0.003), baseline eGFR
      (p = 0.009) and history of nephrolithiasis (p = 0.039). However, multivariate
      analysis revealed that the only independent predictors of postoperative AKI were
      hypertension (p = 0.009) and cigarette smoking (p = 0.024). Conclusion: AKI is a
      common complication of NSS affecting about one-third of the patients. The most
      important risk factors are hypertension and smoking.

PMID- 29662541
TI  - Cabozantinib in the treatment of advanced renal cell carcinoma in adults
      following prior vascular endothelial growth factor targeted therapy: clinical
      trial evidence and experience.
AB  - Cabozantinib is an oral multitargeted tyrosine kinase inhibitor (TKI) that
      potently inhibits MET and AXL, both associated with poor prognosis in renal cell
      carcinoma (RCC), next to vascular endothelial growth factor receptor 2, KIT, FLT3
      and RET. Chronic treatment with vascular endothelial growth factor receptor
      (VEGFR)-targeting sunitinib upregulates MET and AXL in RCC, indicating that
      cabozantinib may be particularly effective in patients with advanced RCC whose
      disease progressed on prior VEGFR-targeted treatment. Cabozantinib (60 mg once
      daily) has been investigated in comparison to everolimus (10 mg once daily) in a
      phase III randomized controlled trial (RCT) in 658 patients with advanced RCC of
      whom 71% had received one prior and 29% had received at least two prior lines of
      VEGR-targeted therapy. This study demonstrated highly significant improved
      progression-free survival of 7.4 months versus 3.9 months with a hazard ratio
      (HR) of 0.51 [95% confidence interval (CI) 0.41-0.62] in favour of cabozantinib.
      Cabozantinib also showed a superior overall survival of 21.4 months versus 16.5
      months (HR 0.66; 95% CI 0.53-0.83). Objective response rate was higher in
      cabozantinib-treated patients, 17% versus 3%. Clinical benefit was shown in all
      subgroups of patients, including in patients with bone or visceral metastases.
      The safety profile was acceptable with manageable side effects. Based on this
      study, cabozantinib is a highly effective approved second-line treatment option
      for patients with advanced RCC with a manageable toxicity profile. Other recently
      approved second-line agents include checkpoint inhibitor nivolumab and VEGF
      targeting agent lenvatinib combined with everolimus. In the absence of predictive
      markers as well as head-to-head comparisons of these three recently approved
      treatments, the choice between these drugs in second-line treatment will probably
      be made based on comorbidities, tolerability of previous treatment and presence
      of high tumour burden with rapidly progressive disease. Future pretreatment
      assessment of MET and AXL tumour aberration may aid clinicians to make a rational
      choice between currently approved second-line treatment options.

PMID- 29662542
TI  - Meta-analysis of studies comparing oncologic outcomes of radical prostatectomy
      and brachytherapy for localized prostate cancer.
AB  - Background: The aim of this study was to compare oncologic outcomes of radical
      prostatectomy (RP) with brachytherapy (BT). Methods: A literature review was
      conducted according to the 'Preferred reporting items for systematic reviews and
      meta-analyses' (PRISMA) statement. We included studies reporting comparative
      oncologic outcomes of RP versus BT for localized prostate cancer (PCa). From each
      comparative study, we extracted the study design, the number and features of the
      included patients, and the oncologic outcomes expressed as all-cause mortality
      (ACM), PCa-specific mortality (PCSM) or, when the former were unavailable, as
      biochemical recurrence (BCR). All of the data retrieved from the selected studies
      were recorded in an electronic database. Cumulative analysis was conducted using
      the Review Manager version 5.3 software, designed for composing Cochrane Reviews
      (Cochrane Collaboration, Oxford, UK). Statistical heterogeneity was tested using
      the Chi-square test. Results: Our cumulative analysis did not show any
      significant difference in terms of BCR, ACM or PCSM rates between the RP and BT
      cohorts. Only three studies reported risk-stratified outcomes of intermediate-
      and high-risk patients, which are the most prone to treatment failure.
      Conclusions: our analysis suggested that RP and BT may have similar oncologic
      outcomes. However, the analysis included a limited number of studies, and most of
      them were retrospective, making it impossible to derive any definitive
      conclusion, especially for intermediate- and high-risk patients. In this
      scenario, appropriate urologic counseling remains of utmost importance.

PMID- 29662543
TI  - Optical improvements in the diagnosis of bladder cancer: implications for
      clinical practice.
AB  - Background: For over 100 years white-light cystoscopy has remained the gold
      standard technique for the detection of bladder cancer (BCa). Some limitations in
      the detection of flat lesions (CIS), the differentiation between inflammation and
      malignancy, the inaccurate determination of the tumor margin status as well as
      the tumor depth, have led to a variety of technological improvements. The aim of
      this review is to evaluate the impact of these improvements in the diagnosis of
      BCa and their effectiveness in clinical practice. Methods: A systematic
      literature search was conducted according to the PRISMA statement to identify
      studies reporting on imaging modalities in the diagnosis of NMIBC between 2000
      and 2017. A two-stage selection process was utilized to determine eligible
      studies. A total of 74 studies were considered for final analysis. Results:
      Optical imaging technologies have emerged as an adjunct to white-light cystoscopy
      and can be classified according to their scope as macroscopic, microscopic and
      molecular. Macroscopic techniques including photodynamic diagnosis (PDD), narrow
      band imaging (NBI) and the Storz Professional Image Enhancement System (IMAGE1 S,
      formerly known as SPIES) are similar to white-light cystoscopy, but are superior
      in the detection of bladder tumors by means of contrast enhancement. Especially
      the detection rate of very mute lesions in the bladder mucosa (CIS) could be
      significantly increased by the use of these methods. Microscopic imaging
      techniques like confocal laser endomicroscopy and optical coherence tomography
      permit a real-time high-resolution assessment of the bladder mucosa at a cellular
      and sub-cellular level with spatial resolutions similar to histology, enabling
      the surgeon to perform an 'optical biopsy'. Molecular techniques are based on the
      combination of optical imaging technologies with fluorescence labeling of cancer
      specific molecular agents like antibodies. This labeling is intended to favor an
      optical distinction between benign and malignant tissue. Conclusions: Optical
      improvements of the standard white-light cystoscopy have proven their benefit in
      the detection of BCa and have found their way into clinical practice. Especially
      the combination of macroscopic and microscopic techniques may improve diagnostic
      accuracy. Nevertheless, HAL-PDD guided cystoscopy is the only approach approved
      for routine use in the diagnosis of BCa by most urological associations in the EU
      and USA to date.

PMID- 29662544
TI  - Sunitinib in the treatment of renal cell carcinoma: an update on recent evidence.
AB  - Sunitinib is a multitarget tyrosine kinase inhibitor endowed mainly by
      antiangiogenic effects, although an indirect inhibitory effect on tumor growth
      and, more recently, a complex activity on antitumor immune response has been
      described. From approval by the US Food and Drug Administration (FDA) in January
      2006, sunitinib represents a key molecule in the treatment of metastatic renal
      cell carcinoma (mRCC) due to the peculiar molecular pathogenesis of this
      neoplasm. Over the past 10 years, clinical trials and real-world experiences
      helped clinicians to understand how, when and for how long to use sunitinib.
      Although a huge amount of data evidenced the relationship existing between
      sunitinib dose intensity and improved clinical outcome, the management of
      sunitinib-induced adverse events is often complex; thus, alternative schedules
      have been proposed over time which allow increased tolerability, without
      decreased daily sunitinib exposure, leading to improved clinical outcomes. To
      date, combinations of sunitinib with other approved targeted agents did not
      demonstrate any significant benefit over its single-agent use, mainly due to
      tolerability issues. Sunitinib has also been tested in the adjuvant setting,
      within the ASSURE and S-TRAC trials, with opposite results; indeed, equivocal
      risk-stratification criteria, as well as immature overall survival (OS) data
      prevent any definitive conclusion on this important issue. Despite being on the
      market for a long time, sunitinib still plays a role as the 'comparator arm' of a
      number of trials in the field of mRCC. Combinations with immune checkpoint
      inhibitors and vaccines look promising; once again, sunitinib can help us to
      optimize mRCC management.

PMID- 29662545
TI  - Prostate artery embolization: a new, minimally invasive treatment for lower
      urinary tract symptoms secondary to prostate enlargement.
AB  - Prostate artery embolization (PAE) is emerging as a safe and efficacious
      treatment which approaches benign prostatic obstruction (BPO) from a unique
      perspective. This brings with it distinct advantages and solutions, which we
      discuss along with cost, evidence, complications and disadvantages.

PMID- 29662546
TI  - Combination of immunotherapy with chemotherapy and radiotherapy in lung cancer:
      is this the beginning of the end for cancer?
AB  - Immune checkpoint inhibitors have significantly improved overall survival with an
      acceptable safety profile in a substantial proportion of non-small cell lung
      cancer (NSCLC) patients. However, not all patients are sensitive to immune
      checkpoint blockade and, in some cases, programmed death 1 (PD-1) or programmed
      death ligand 1 (PD-L1) inhibitors accelerate tumor progression. Several
      combination strategies are under evaluation, including the concomitant or
      sequential evaluation of chemotherapy or radiotherapy with immunotherapy. The
      current review provides an overview on the molecular rationale for the
      investigation of combinatorial approaches with chemotherapy or radiotherapy.
      Moreover, the results of completed clinical studies will be reported.

PMID- 29662548
TI  - First-line treatment of ovarian cancer: questions and controversies to address.

PMID- 29662547
TI  - PD-L1 expression testing in non-small cell lung cancer.
AB  - In recent years, immunotherapy has revolutionized and changed the standard of
      care in patients with advanced non-small cell lung cancer (NSCLC). Immune
      checkpoint inhibitors, fundamentally those that act by blocking the programmed
      cell death receptor-1 (PD-1) and its ligand the programmed cell death ligand-1
      (PD-L1) have emerged as novel treatment strategies in NSCLC, demonstrating
      undoubted superiority over chemotherapy in terms of efficacy. Several of these
      immune checkpoint modulators have recently gained regulatory approval for the
      treatment of advanced NSCLC, such as nivolumab, atezolizumab and pembrolizumab in
      first-line (only the latter) and second-line settings, and more recently,
      durvalumab as maintenance after chemoradiotherapy in locally advanced disease.
      There is consensus that PD-L1 expression on tumor cells predicts responsiveness
      to PD-1 inhibitors in several tumor types. Hence PD-L1 expression evaluated by
      immunohistochemistry (IHC) is currently used as a clinical decision-making tool
      to support the use of checkpoint inhibitors in NSCLC patients. However, the value
      of PD-L1 as the 'definitive' biomarker is controversial as its testing is puzzled
      by multiple unsolved issues such as the use of different staining platforms and
      antibodies, the type of cells in which PD-L1 is assessed (tumor versus immune
      cells), thresholds used for PD-L1-positivity, or the source and timing for sample
      collection. Therefore, newer biomarkers such as tumor mutation burden and
      neoantigens as well as biomarkers reflecting host environment (microbiome) or
      tumor inflamed microenvironment (gene expression signatures) are being explored
      as more reliable and accurate alternatives to IHC for guiding treatment selection
      with checkpoint inhibitors in NSCLC.

PMID- 29662549
TI  - Tumour necrosis factor, interferon-gamma and interleukins as predictive markers
      of antiprogrammed cell-death protein-1 treatment in advanced non-small cell lung
      cancer: a pragmatic approach in clinical practice.
AB  - Background: The emergence of novel antiprogrammed cell death protein-1 (PD-1)
      inhibitors in non-small cell lung cancers (NSCLC) has revolutionized the
      therapeutic landscape of this disease. Although overall survival (OS) has
      improved in the first- and second-line therapy settings for advanced NSCLC, the
      benefit is not universal. In a climate of global scrutiny for healthcare costs
      and potential for toxicities related to immunotherapy, appropriate patient
      selection is crucial. The aim of this study was to evaluate potential prognostic
      and predictive biomarkers interferon-gamma (IFN-gamma), tumour necrosis factor
      alpha (TNF-alpha) and a panel of interleukins (ILs) in the peripheral blood, and
      assess any correlation with response to anti-PD-1 inhibition, progression-free
      survival and OS in NSCLC patients. Methods: We prospectively studied 26 NSCLC
      patients that received immunotherapy (either pembrolizumab or nivolumab). IFN
      gamma, TNF-alpha, IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10 and IL-12 were
      analyzed by flow cytometry at the time of diagnosis and at 3 months after
      initiation of anti-PD-1 inhibition. Results: Increased cytokine values (IFN
      gamma, TNF-alpha, IL-1beta, IL-2, IL-4, IL-6 and IL-8) at the time of diagnosis
      and at 3 months after initiation of treatment were significantly correlated with
      improved response to immunotherapy and prolonged OS. There was no correlation
      between cytokine levels and programmed cell death ligand-1 (PD-L1) expression.
      Conclusions: Increased IFN-gamma, TNF-alpha, IL-1beta, IL-2, IL-4, IL-5, IL-6, IL
      8, IL-10 and IL-12 levels resulted in better response to NSCLC anti-PD-1
      inhibition and longer survival, and this could potentially play an important role
      in selecting patients that would benefit from anti-PD-1 inhibitors.

PMID- 29662550
TI  - Radiotherapy and checkpoint inhibitors: a winning new combination?
AB  - Immune checkpoint blockade has recently emerged as an important therapeutic
      approach to the management of malignancies across multiple disease settings.
      Concomitantly, there has been an increasing appreciation for the role of
      radiotherapy in eliciting and promoting tumor-directed immune responses. In this
      review, we discuss the clinical evidence to date on combinations of radiotherapy
      with immune checkpoint inhibitors, both from the standpoint of safety and
      efficacy. We highlight important but yet-unanswered questions for this
      combination approach, as well as their implications for future prospective
      studies.

PMID- 29662551
TI  - Dissecting the Dissociation Patterns of Fucosylated Glycopeptides Undergoing CID:
      A Case Study in Improving Automated Glycopeptide Analysis Scoring Algorithms.
AB  - The need to investigate the fragmentation of fucosylated glycopeptides is driven
      by recent work showing that at least one, and perhaps many, glycopeptide analysis
      scoring algorithms are less effective at identifying fucosylated glycopeptides
      than non-fucosylated glycopeptides. Herein, we study the CID fragmentation
      characteristics of fucosylated glycopeptides and the scoring rules of the
      glycopeptide analysis software, GlycoPep Grader, in an effort to improve
      automated assignments of these important glycopeptides. We identified some
      prominent product ions from a common fragmentation pathway of fucosylated
      glycopeptides that were not accounted for in the scoring rules. Based on this
      finding, we propose new scoring rules for fucosylated glycopeptides that can be
      incorporated into GlycoPep Grader and other similar analysis software tools to
      more accurately identify these species. The approach used here, to improve one
      particular scoring algorithm, could henceforth be used to improve any other
      algorithm that assigns glycopeptides based on their MS/MS data.

PMID- 29662552
TI  - Strategies for enumeration of circulating microvesicles on a conventional flow
      cytometer: Counting beads and scatter parameters.
AB  - Enumeration of circulating microvesicles (MVs) by conventional flow cytometry is
      accomplished by the addition of a known amount of counting beads and calculated
      from the formula: MV/MUl = (MV count/bead count) * final bead concentration. We
      sought to optimize each variable in the equation by determining the best
      parameters for detecting 'MV count' and examining the effects of different bead
      preparations and concentrations on the final calculation. Three commercially
      available bead preparations (TruCount, Flow-Count and CountBright) were tested,
      and MV detection on a BD FACSCanto was optimized for gating by either forward
      scatter (FSC) or side scatter (SSC); the results were compared by calculating
      different subsets of MV on a series of 74 typical patient plasma samples. The
      relationship between the number of beads added to each test and the number of
      beads counted by flow cytometry remained linear over a wide range of bead
      concentrations (R2 >= 0.997). However, TruCount beads produced the most
      consistent (concentration variation = 3.8%) calculated numbers of plasma
      CD41+/Annexin V+ MV, which were significantly higher from that calculated using
      either Flow-Count or CountBright (p < 0.001). The FACSCanto was able to resolve
      0.5 MUm beads by FSC and 0.16 MUm beads by SSC, but there were significantly more
      background events using SSC compared with FSC (3113 vs. 470; p = 0.008). In
      general, sample analysis by SSC resulted in significantly higher numbers of MV (p
      < 0.0001) but was well correlated with enumeration by FSC for all MV subtypes
      (rho = 0.62-0.89, p < 0.0001). We conclude that all counting beads provided
      linear results at concentrations ranging from 6 beads/MUl to 100 beads/MUl, but
      TruCount was the most consistent. Using SSC to gate MV events produced high
      background which negatively affected counting bead enumeration and overall MV
      calculations. Strategies to reduce SSC background should be employed in order to
      reliably use this technique.

PMID- 29662553
TI  - Plasma fatty acid levels and gene expression related to lipid metabolism in
      peripheral blood mononuclear cells: a cross-sectional study in healthy subjects.
AB  - Background: Solid evidence indicates that intake of marine n-3 fatty acids lowers
      serum triglycerides and that replacing saturated fatty acids (SFA) with
      polyunsaturated fatty acids (PUFA) reduces plasma total cholesterol and LDL
      cholesterol. The molecular mechanisms underlying these health beneficial effects
      are however not completely elucidated. The aim of this study was therefore to
      investigate the expression of genes related to lipid metabolism in peripheral
      blood mononuclear cells (PBMC) depending on the plasma levels of n-6 and n-3
      fatty acids and the SFA to PUFA ratio. Methods: Fifty-four healthy subjects were
      grouped into tertiles (n = 18) based on plasma levels of n-6 and n-3 fatty acids
      and the SFA to PUFA ratio. The PBMC gene expression levels among subjects in the
      highest versus the lowest tertiles were compared. In total, 285 genes related to
      cholesterol and triglyceride metabolism were selected for this explorative study.
      Results: Among the 285 selected genes, 161 were defined as expressed in the
      PBMCs. The plasma SFA to PUFA ratio was associated with the highest number of
      significantly different expressed genes (25 gene transcripts), followed by plasma
      n-6 fatty acid level (15 gene transcripts) and plasma n-3 fatty acid level (8
      gene transcripts). In particular, genes involved in cholesterol homeostasis were
      significantly different expressed among subjects with high compared to low plasma
      SFA to PUFA ratio. Conclusion: Genes involved in lipid metabolism were
      differentially expressed in PBMCs depending on the plasma fatty acid levels. This
      finding may increase our understanding of how fatty acids influence lipid
      metabolism at a molecular level in humans.

PMID- 29662555
TI  - Message from the Editor-in-Chief: Theranostic Imaging in 2018.

PMID- 29662554
TI  - Effect of beta-hydroxy-beta-methylbutyrate on miRNA expression in differentiating
      equine satellite cells exposed to hydrogen peroxide.
AB  - Background: Skeletal muscle injury activates satellite cells to initiate
      processes of proliferation, differentiation, and hypertrophy in order to
      regenerate muscle fibers. The number of microRNAs and their target genes are
      engaged in satellite cell activation. beta-Hydroxy-beta-methylbutyrate (HMB) is
      known to prevent exercise-induced muscle damage. The purpose of this study was to
      evaluate the effect of HMB on miRNA and relevant target gene expression in
      differentiating equine satellite cells exposed to H2O2. We hypothesized that HMB
      may regulate satellite cell activity, proliferation, and differentiation, hence
      attenuate the pathological processes induced during an in vitro model of H2O2
      related injury by changing the expression of miRNAs. Methods: Equine satellite
      cells (ESC) were isolated from the samples of skeletal muscle collected from
      young horses. ESC were treated with HMB (24 h) and then exposed to H2O2 (1 h).
      For the microRNA and gene expression assessment microarrays, technique was used.
      Identified miRNAs and genes were validated using real-time qPCR. Cell viability,
      oxidative stress, and cell damage were measured using colorimetric method and
      flow cytometry. Results: Analysis of miRNA and gene profile in differentiating
      ESC pre-incubated with HMB and then exposed to H2O2 revealed difference in the
      expression of 27 miRNAs and 4740 genes, of which 344 were potential target genes
      for identified miRNAs. Special attention was focused on differentially expressed
      miRNAs and their target genes involved in processes related to skeletal muscle
      injury. Western blot analysis showed protein protection in HMB-pre-treated group
      compared to control. The viability test confirmed that HMB enhanced cell survival
      after the hydrogen peroxide exposition. Conclusions: Our results suggest that ESC
      pre-incubated with HMB and exposed to H2O2 could affect expression on miRNA
      levels responsible for skeletal muscle development, cell proliferation and
      differentiation, and activation of tissue repair after injury. Enrichment
      analyses for targeted genes revealed that a large group of genes was associated
      with the regulation of signaling pathways crucial for muscle tissue development,
      protein metabolism, muscle injury, and regeneration, as well as with oxidative
      stress response.

PMID- 29662556
TI  - Radiomics and Deep Learning in Clinical Imaging: What Should We Do?

PMID- 29662557
TI  - CT Radiomics in Thoracic Oncology: Technique and Clinical Applications.
AB  - Precision medicine offers better treatment options and improved survival for
      cancer patients based on individual variability. As the success of precision
      medicine depends on robust biomarkers, the requirement for improved imaging
      biomarkers that reflect tumor biology has grown exponentially. Radiomics, the
      field of study in which high-throughput data are generated and large amounts of
      advanced quantitative features are extracted from medical images, has shown great
      potential as a source of quantitative biomarkers in the field of oncology.
      Radiomics provides quantitative information about the morphology, texture, and
      intratumoral heterogeneity of the tumor itself as well as features related to
      pulmonary function. Hence, radiomics data can be used to build descriptive and
      predictive clinical models that relate imaging characteristics to tumor biology
      phenotypes. In this review, we describe the workflow of CT radiomics, types of CT
      radiomics, and its clinical application in thoracic oncology.

PMID- 29662558
TI  - Radiomics as a Quantitative Imaging Biomarker: Practical Considerations and the
      Current Standpoint in Neuro-oncologic Studies.
AB  - Radiomics utilizes high-dimensional imaging data to discover the association with
      diagnostic, prognostic, predictive endpoint or radiogenomics. It is an emerging
      field of study that potentially depicts the intratumoral heterogeneity from
      quantitative and classified high-throughput data. The radiomics approach has an
      analytic pipeline where the imaging features are extracted, processed and
      analyzed. At this point, special data handling is essential because it faces
      issues of a high-dimensional biomarker compared to a single biomarker approach.
      This article describes the potential role of radiomics in oncologic studies, the
      basic analytic pipeline and special data handling with high-dimensional data to
      facilitate the radiomics approach as a tool for personalized medicine in
      oncology.

PMID- 29662560
TI  - Impact of 68Ga-DOTA-Peptide PET/CT on the Management of Gastrointestinal
      Neuroendocrine Tumour (GI-NET): Malaysian National Referral Centre Experience.
AB  - Purpose: The National Cancer Institute is the only referral centre in Malaysia
      that provides 68Ga-DOTA-peptide imaging. The purpose of this study is to
      determine the impact of 68Ga-DOTA-peptide PET/CT on the management of
      gastrointestinal neuroendocrine tumours (GI-NET). Materials and Methods: A cross
      sectional study was performed to review the impact of 68Ga-DOTA-peptide (68Ga
      DOTATATE or 68Ga-DOTATOC) PET/CT on patients with biopsy-proven GI-NET between
      January 2011 and December 2015. Suspected NET was excluded. Demographic data,
      tumoral characteristics, change of disease stage, pre-PET intended management and
      post-PET management were evaluated. Results: Over a 5-year period, 82 studies of
      68Ga-DOTA-peptide PET/CT were performed on 44 GI-NET patients. The most common
      primary site was the rectum (50.0%) followed by the small bowel, stomach and
      colon. Using WHO 2010 grading, 40.9% of patients had low-grade (G1) tumour, 22.7%
      intermediate (G2) and 4.5% high (G3). Of ten patients scheduled for pre-operative
      staging, 68Ga-DOTA-peptide PET/CT only led to therapeutic change in three
      patients. Furthermore, false-negative results of 68Ga-DOTA-peptide PET/CT were
      reported in one patient after surgical confirmation. However, therapeutic changes
      were seen in 20/36 patients (55.6%) scheduled for post-surgical restaging or
      assessment of somatostatin analogue (SSA) eligibility. When 68Ga-DOTA-peptide
      PET/CT was used for monitoring disease progress during systemic treatment
      (sandostatin, chemotherapy, everolimus and PRRT) in metastatic disease, impact on
      management modification was seen in 19/36 patients (52.8%), of which 84.2% had
      inter-modality change (switch to everolimus, chemotherapy or PRRT) and 15.8% had
      intra-modality change (increased SSA dosage). Conclusions: 68Ga-DOTA-peptide
      PET/CT has a significant impact on management decisions in GI-NET patients as it
      can provide additional information on occult metastasis/equivocal lesions and
      supply the clinician an opportunity to select patients for targeted therapy.

PMID- 29662559
TI  - Deep Learning in Nuclear Medicine and Molecular Imaging: Current Perspectives and
      Future Directions.
AB  - Recent advances in deep learning have impacted various scientific and industrial
      fields. Due to the rapid application of deep learning in biomedical data,
      molecular imaging has also started to adopt this technique. In this regard, it is
      expected that deep learning will potentially affect the roles of molecular
      imaging experts as well as clinical decision making. This review firstly offers a
      basic overview of deep learning particularly for image data analysis to give
      knowledge to nuclear medicine physicians and researchers. Because of the unique
      characteristics and distinctive aims of various types of molecular imaging, deep
      learning applications can be different from other fields. In this context, the
      review deals with current perspectives of deep learning in molecular imaging
      particularly in terms of development of biomarkers. Finally, future challenges of
      deep learning application for molecular imaging and future roles of experts in
      molecular imaging will be discussed.

PMID- 29662561
TI  - A Systematic Comparative Evaluation of 68Ga-Labeled RGD Peptides Conjugated with
      Different Chelators.
AB  - Purpose: The present paper reports a systematic study on the effect of
      bifunctional chelators (BFC) namely, NOTA, DOTA, and DTPA, on the radiochemical
      formulation, in vitro stability, and in vivo biological properties of 68Ga
      labeled RGD peptide derivatives. Methods: The three RGD conjugates namely, NOTA
      Bn-E-[c(RGDfk)]2, DOTA-Bn-E-[c(RGDfk)]2, and DTPA-Bn-E-[c(RGDfk)]2 were
      radiolabeled with 68Ga and the radiolabeling was optimized with respect to the
      ligand amount, radiolabeling time, and temperature. Further, the 68Ga complexes
      were assessed for their in vitro and in vivo stabilities. The biodistribution
      studies of the three radiolabeled conjugates were carried out in C57BL/6 mice
      bearing melanoma tumor at 30 min and 1 h post-adimistration. Results: NOTA-Bn-E
      [c(RGDfk)]2 could be radiolabeled with 68Ga at room temperature while DOTA-Bn-E
      [c(RGDfk)]2 and DTPA-Bn-E-[c(RGDfk)]2 were radiolabeled at high temperature. 68Ga
      NOTA-Bn-E-[c(RGDfk)]2 was found to be the most kinetically rigid in in vitro
      stability assay. The uptake of the three radiolabeled peptide conjugates in
      melanoma tumor was comparable at 1 h post-administration (NOTA; DOTA; DTPA (%
      I.D./g):: 2.78 +/- 0.38; 3.08 +/- 1.1; 3.36 +/- 0.49). However, the
      tumor/background ratio of 68Ga-NOTA-Bn-E-[c(RGDfk)]2 was the best amongst the
      three radiotracers. 68Ga-complexes of NOTA-Bn-E-[c(RGDfk)]2 and DOTA-Bn-E
      [c(RGDfk)]2 showed excellent in vivo stability while 68Ga-DTPA-Bn-E-[c(RGDfk)]2
      showed significant metabolic degradation. Conclusion: These studies show that
      68Ga-NOTA-Bn-E-[c(RGDfk)]2 would be the most appropriate 68Ga-labeled radiotracer
      and the most amenable for kit formulation.

PMID- 29662562
TI  - The Predictive Values of Lesion Size, F-18 FDG Avidity and I-131 Avidity for the
      Clinical Outcome of I-131 Treatment in Patients with Metastatic Differentiated
      Thyroid Carcinoma Only in the Lung.
AB  - Purpose: We aimed to evaluate the prognostic values of radiography, F-18 FDG PET,
      and I-131 whole body scans in patients with lung-only metastasis from
      differentiated thyroid carcinoma (DTC). Methods: Between 1998 and 2013, we
      included 31 patients (F: 26, M: 5) with lung-only metastasis from DTC who had
      been treated with I-131 and underwent PET. Lung metastasis was categorized
      according to the size (macronodular >=1.0 cm vs. micronodular <1.0 cm), FDG
      avidity (avid vs. non-avid), and I-131 avidity (avid vs. non-avid). Progression
      free survival (PFS) was evaluated for each patient. Results: Among 31 patients,
      seven (23%) had macronodular lung metastasis, 26 (84%) had FDG avid lung
      metastasis, and 16 (52%) had I-131 avid lung metastasis. During the median follow
      up period of 9.4 y, median PFS was 6.1 y. Based on Kaplan-Meier analysis,
      macronodular lung metastasis (p = 0.017) and I-131 non-avid lung metastasis (p =
      0.059) were significantly associated with worse outcomes, but FDG avid lung
      metastasis was not (p = 0.135). Patients with FDG non-avid lung metastasis did
      not experience disease progression during follow-up, while 11 of 26 patients
      (42%) experienced disease progression. Based on univariate analysis, the hazard
      ratio for a poor prognosis was 3.78 (p = 0.029) for macronodular lung metastasis
      and 3.29 (p = 0.079) for I-131 non-avid lung metastasis. Conclusions:
      Macronodular and I-131 non-avid lung metastasis were associated with a poor
      prognosis in lung-only metastasis from DTC. Although FDG avid lung metastasis may
      be associated with a poor prognosis, a larger-scale study is needed.

PMID- 29662563
TI  - 123I-Labeled oxLDL Is Widely Distributed Throughout the Whole Body in Mice.
AB  - Purpose: Oxidized low-density lipoprotein (oxLDL) plays a key role in endothelial
      dysfunction, vascular inflammation, and atherogenesis. The aim of this study was
      to assess blood clearance and in vivo kinetics of radiolabeled oxLDL in mice.
      Methods: We synthesized 123I-oxLDL by the iodine monochloride method, and
      performed an uptake study in CHO cells transfected with lectin-like oxLDL
      receptor-1 (LOX-1). In addition, we evaluated the consistency between the 123I
      oxLDL autoradiogram and the fluorescence image of DiI-oxLDL after intravenous
      injection for both spleen and liver. Whole-body dynamic planar images were
      acquired 10 min post injection of 123I-oxLDL to generate regional time-activity
      curves (TACs) of the liver, heart, lungs, kidney, head, and abdomen. Regional
      radioactivity for those excised tissues as well as the bladder, stomach, gut, and
      thyroid were assessed using a gamma counter, yielding percent injected dose (%ID)
      and dose uptake ratio (DUR). The presence of 123I-oxLDL in serum was assessed by
      radio-HPLC. Results: The cellular uptakes of 123I-oxLDL were identical to those
      of DiI-oxLDL, and autoradiograms and fluorescence images also exhibited
      consistent distributions. TACs after injection of 123I-oxLDL demonstrated
      extremely fast kinetics. The radioactivity uptake at 10 min post-injection was
      highest in the liver (40.8 +/- 2.4% ID). Notably, radioactivity uptake was
      equivalent throughout the rest of the body (39.4 +/- 2.7% ID). HPLC analysis
      revealed no remaining 123I-oxLDL or its metabolites in the blood. Conclusion:
      123I-OxLDL was widely distributed not only in the liver, but also throughout the
      whole body, providing insight into the pathophysiological effects of oxLDL.

PMID- 29662565
TI  - Follicular Lymphoma mimicking Metastatic Nodes on the F-18 FDG PET/CT and MRI for
      Staging of Endometrial Cancer.
AB  - A 53-year-old woman was diagnosed with endometrial carcinoma by vaginal bleeding.
      F-18 fluorodeoxy glucose positron emission tomography PET/CT (F-18 FDG PET/CT)
      scan for staging showed intense focal FDG uptake in the endometrium suggesting
      endometrial malignancy. PET/CT showed multiple node uptakes in the pericaval
      region, paraaortic region, common iliac, and both internal iliac and external
      iliac regions suggesting multiple pelvic and retroperitoneal node metastases. MRI
      showed multiple metastatic lymphadenopathy in the retroperitoneum and pelvic
      cavity. Pathologic diagnosis performed with dissected pelvic and paraaortic nodes
      was confirmed as a follicular malignant lymphoma positive for B-cell lymphoma
      2(Bcl-2) stain, not the metastatic node of primary endometrioid carcinoma.

PMID- 29662564
TI  - Dual Pathologies of Parathyroid Adenoma and Papillary Thyroid Cancer on
      Fluorocholine and Fluorodeoxyglucose PET/CT.
AB  - 18F-Fluorocholine (FCH) PET/CT is evolving as a functional imaging modality for
      the preoperative imaging of abnormal parathyroid tissue(s) helping to localize
      eutopic and ectopic parathyroid tissue and limit the extent of surgery. FCH
      PET/CT may show incidental uptake in various thyroid lesions necessitating
      further evaluation, whereas the role of 18F-fluorodeoxyglucose (FDG) PET/CT in
      the detection of incidental thyroid nodules is well documented. The case of a
      middle-aged woman with dual pathology of parathyroid adenoma and papillary
      thyroid cancer detected on FCH and FDG PET/CT is presented.

PMID- 29662566
TI  - Focal Increased Tc-99m MDP Uptake in the Nutrient Foramen of the Femoral
      Diaphysis on Bone SPECT/CT.
AB  - We present images of an 83-year-old female with a history of osteoporosis and
      bilateral total knee replacement arthroplasty, referred for bone scintigraphy and
      single-photon emission computed tomography (SPECT)/computed tomography (CT),
      owing to left knee pain. No trauma to, or intense exercise of, the knee was
      reported. The bone scan and SPECT/CT revealed a focally increased Tc-99m
      methylene diphosphonate (MDP) uptake in the medial cortex of the left femoral
      diaphysis with matched linear radiolucency on CT images. This was misinterpreted
      as atypical femoral stress fracture; however, focal stress reaction injury to the
      nutrient foramen was confirmed on contrast-enhanced magnetic resonance imaging.

PMID- 29662567
TI  - Integrated Imaging Characterization of Adrenal Adenoma: False-Positive
      Metaiodobenzylguanidine (MIBG) Findings of Adrenal Scintigraphy.
AB  - Background: Evaluation of a patient with melanoma in whom an adrenal mass was
      detected on CT and MR during follow-up and further characterized with PET-CT and
      MIBG scintigraphy. Case Report: In this case report, we describe a patient with
      melanoma in whom an adrenal mass was detected on CT and MRI during post-surgical
      follow-up and was further characterized with radionuclide studies consisting of
      PET-CT and MIBG scintigraphy. Although the results of imaging studies suggested
      that the mass was a pheochromocytoma, a cortical adrenal adenoma was
      histologically proven. Conclusions: Integrated structural and functional imaging
      is recommended to characterize adrenal tumors; however, mistakes may occur and
      therefore careful imaging evaluation is required.

PMID- 29662568
TI  - Imaging Findings in a Rare Case of Leiomyomatosis Peritonealis Disseminata with
      Malignant Transformation.
AB  - Background: Leiomyomatosis peritonealis disseminata (LPD) is a rare condition
      characterized by formation of multiple leiomyomas in the abdominal and pelvic
      peritoneum. Malignant transformation of LPD is an extremely rare occurrence. We
      hereby report a case of a middle-aged female who was subsequently diagnosed with
      leiomyomatosis peritonealis disseminata with a few of the lesions showing
      malignant transformation. Case Report: A forty-year-old female with a history of
      hysterectomy presenting with vague abdominal pain was completely evaluated with
      ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI)
      and was subsequently diagnosed with leiomyomatosis peritonealis disseminata. The
      imaging findings of leiomyomatosis peritonealis disseminata were correlated with
      and confirmed by a histopathologic examination of the excision biopsy specimen.
      Conclusions: The imaging findings were found to be specific for leiomyomatosis
      peritonealis disseminata with a malignant transformation.

PMID- 29662569
TI  - Percutaneous Transhepatic Biliary Stenting with Uncovered Self-Expandable
      Metallic Stents in Patients with Malignant Biliary Obstruction - Efficacy and
      Survival Analysis.
AB  - Background: The aim of this study was to assess short- and long-term outcomes of
      malignant biliary obstruction (MBO) treatment by percutaneous transhepatic
      biliary stenting (PTBS) with uncovered selfexpandable metallic stents (SEMS), and
      to identify predictors of survival. Material/Methods: A nine-year, single-centre
      study from a prospectively collected database included 222 patients with
      inoperable MBO treated by PTBS with uncovered nitinol SEMS. Results: Technical
      and clinical success rates were 95.9% and 82.4%, respectively. The total rate of
      postprocedural complications was 14.4%. The mean durations of the primary and
      secondary stent patency were 114.7+/-15.1 and 146.4+/-21.2 days, respectively.
      The 30-day mortality rate was 15.3% with no procedure-related deaths. The mean
      estimated length of survival was 143.3+/-20.6 days. Independent predictors
      increasing the risk of death included higher than 115 MUmol/L serum bilirubin 2-5
      days after biliary stenting (HR 3.274, P=0.019), distal (non-hilar) obstruction
      of the bile ducts (HR 3.711, P=0.008), Bismuth-Corlette type IV stricture (HR
      2.082, P=0.008), obstruction due to gallbladder cancer (HR 31.029, P=0.012) and
      only partial drainage of liver parenchyma (HR 4.158, P=0.040). Conclusions: PTBS
      with uncovered SEMS is an effective and safe method for palliative treatment of
      MBO. Serum bilirubin higher than 115 MUmol/L 2-5 days after the procedure has a
      significant negative impact on patients' survival. Lower survival is also
      determined by distal bile duct obstruction, Bismuth- Corlette type IV stricture,
      biliary obstruction caused by gallbladder cancer and when only partial liver
      drainage is applied.

PMID- 29662570
TI  - Inter-Observer Agreement of Whole-Body Computed Tomography in Staging and
      Response Assessment in Lymphoma: The Lugano Classification.
AB  - Background: To assess inter-observer agreement of whole-body computed tomography
      (WBCT) in staging and response assessment in lymphoma according to the Lugano
      classification. Material/Methods: Retrospective analysis was conducted of 115
      consecutive patients with lymphomas (45 females, 70 males; mean age of 46 years).
      Patients underwent WBCT with a 64 multi-detector CT device for staging and
      response assessment after a complete course of chemotherapy. Image analysis was
      performed by 2 reviewers according to the Lugano classification for staging and
      response assessment. Results: The overall inter-observer agreement of WBCT in
      staging of lymphoma was excellent (k=0.90, percent agreement=94.9%). There was an
      excellent inter-observer agreement for stage I (k=0.93, percent agreement=96.4%),
      stage II (k=0.90, percent agreement=94.8%), stage III (k=0.89, percent
      agreement=94.6%) and stage IV (k=0.88, percent agreement=94%). The overall inter
      observer agreement in response assessment after a completer course of treatment
      was excellent (k=0.91, percent agreement=95.8%). There was an excellent inter
      observer agreement in progressive disease (k=0.94, percent agreement=97.1%),
      stable disease (k=0.90, percent agreement=95%), partial response (k=0.96, percent
      agreement=98.1%) and complete response (k=0.87, Percent agreement=93.3%).
      Conclusions: We concluded that WBCT is a reliable and reproducible imaging
      modality for staging and treatment assessment in lymphoma according to the Lugano
      classification.

PMID- 29662571
TI  - Imaging in Sternal Tumours: A Pictorial Review.
AB  - The sternum is an uncommon site for neoplastic involvement and metastases are far
      commoner than primary neoplasms. Of the primary tumours, malignant lesions are
      more frequent than the benign lesions. Early diagnosis and treatment is prudent
      in such neoplasms not only to halt disease progression but also to prevent
      circulatory compromise resulting from the mass effect on the mediastinum. Sound
      knowledge of neoplasms affecting the sternum and their imaging appearance is
      essential to arrive at an early diagnosis and also to obviate biopsy in cases
      with classical imaging findings. Neoplastic involvement of the sternum is
      extremely unusual and should be considered malignant unless proven otherwise.
      Imaging may help in arriving at the diagnosis of these lesions, together with
      other factors such as patient's age, type of lesion (lytic/sclerotic or mixed),
      matrix mineralization, multiplicity and involvement of other sites.

PMID- 29662572
TI  - Clinical Audit of Paediatric Magnetic Resonance Imaging Under Sedation at a
      Nigerian Tertiary Institution.
AB  - Background: Magnetic resonance imaging (MRI) in paediatric patients requires them
      to be calm during the procedure to avoid motion artefacts in the acquired images.
      Sedation and/or anaesthesia is a way to achieve this. We evaluated all paediatric
      MRI sedations since installation of an MRI device in our hospital.
      Material/Methods: We retrospectively reviewed 69 paediatric MRI sedations
      performed over a 5-year period using records of patients' biodata, MRI date,
      indication, findings and scan time, sources of referral, body region scanned,
      type, dose, related adverse events and route of administration of sedatives as
      well as image quality. Results: The median age and weight of the patients were 24
      months {range of 0.3 months (10 days) to 132 months (11 years)} and 11.5 kg
      (range of 2.6 kg to 42 kg), respectively. Males constituted 50.7% of the
      patients. Most participants (94.2%) were in-patients of the hospital, mainly
      (60.0%) referred from the paediatric unit, with slightly over one third (36.2%)
      of the studies performed in 2015. The commonest indication and scanned body
      region were macrocephaly (18.8%) and the brain (76.8%), respectively.
      Hydrocephalus (17.4%) was the commonest MRI finding. Sedation was planned in 66
      (95.7%) patients and was successful in 68 (98.6%). Midazolam and the IV route
      were the commonest sedative agent and route of administration, respectively.
      Image quality determined by age was fair to good in 68 (98.6%) patients with only
      1 patient requiring re-scanning due to motion blur. No adverse events with
      sedation were recorded. Conclusions: Midazolam via the IV route with or without
      oral route is the drug of choice for MRI sedation in children in our institution
      with a success rate of about 99%.

PMID- 29662573
TI  - Creating Order Out of Chaos - Role of Antenatal Ultrasound in Diagnosis.
AB  - Background: Congenital high airway obstruction syndrome (CHAOS) is a rare fetal
      anomaly characterized by obstruction of the higher fetal airway. This could be
      either complete or incomplete and is more commonly seen at the subglottic level,
      resulting in a spectrum of characteristic secondary features. Case Report: In
      this case study, we report two cases of CHAOS with one showing laryngeal atresia
      and the other, tracheal atresia. Both these cases showed characteristic findings
      on a detailed, meticulous USG examination which led to this diagnosis.
      Conclusions: Early and accurate diagnosis offers a window of opportunity for
      parental counseling and management using procedures such as EXIT (ex-utero
      intrapartum procedure). Earlier, CHAOS was thought to be incompatible with life;
      however, with the advent of ex-utero intrapartum procedure, a few cases of post
      natal survival have been noted in the literature. In this article, we emphasize
      the sonographic findings found in CHAOS. Early diagnosis offers an opportunity
      for a intrauterine fetal intervention in potentially lethal cases.

PMID- 29662574
TI  - Postnatal Evaluation of Congenital Chest Pathologies Using a Low-Dose Computed
      Tomography (CT) Protocol - a Pictorial Review.
AB  - Computed tomography with its excellent spatial and temporal resolution remains a
      valuable diagnostic modality in pediatrics. On the other hand an increasing
      attention has been placed on the radiation risks associated with CT imaging,
      especially in children. In recent years, many advances in CT hardware and
      software, for example, automatic exposure control tools and iterative
      reconstruction techniques, have allowed for a reduction of applied radiation
      doses while maintaining image quality. The purpose of this paper is to present
      our protocol for chest CT imaging in the youngest age group, together with a
      pictorial review of congenital pathologies of the chest, and to emphasize factors
      that optimize postnatal CT imaging in infants. In our opinion, modern CT imaging
      with the use of dose reduction techniques and iterative reconstructions allows
      for a proper visualization of chest pathologies in small children, which has no
      influence on observer performance. The presented review of low-dose diagnostic
      images of a wide spectrum of congenital pathologies may serve as an example of
      routine utilization of the current concepts in pediatric CT optimization.

PMID- 29662575
TI  - Autoimmune Hypophysitis Presenting as Solid-Cystic Mass Managed Conservatively.
AB  - Background: Autoimmune hypophysitis (AH) is a rare inflammatory condition of the
      pituitary gland and usually affects women of childbearing age. It commonly leads
      to pituitary dysfunction. Moreover, pituitary enlargement may lead to compressive
      symptoms, which necessitates urgent surgical decompression. Resection of the
      pituitary gland causes iatrogenic hypopituitarism which requires lifelong
      hormonal supplementation. With an increasing number of suspected cases of
      pituitary diseases, there has been a paradigm shift in the management by
      conservative measures, especially, when surgery is not urgently needed. Case
      Report: We report a case of AH in a premenopausal woman presenting with headache.
      MRI revealed a solid-cystic mass involving the anterior lobe of the pituitary
      gland. The infundibulum was also thickened and enhancing; however, it was still
      in the midline. Ancillary MRI findings and hormonal profile were favouring the
      diagnosis of AH over pituitary neoplasm. The patient was managed conservatively
      with high doses of glucocorticoids, which resulted in prompt resolution of the
      lesion. During subsequent follow-up over 6 years, there was no recurrence and
      partial restoration of the pituitary function was seen. This case is interesting
      due to an unusual MRI appearance of AH, presenting as a solid-cystic mass.
      Moreover, disease resolution with conservative treatment strengthens the approach
      to limit surgery to those patients with compressive symptoms or uncertain
      diagnosis. Conclusions: AH should be included in the differential diagnosis of
      solid-cystic pituitary masses along with clinical correlation, which includes
      early involvement of ACTH and TSH and a relatively rapid development of
      hypopituitarism. In uncertain cases or with lack of compressive symptoms, a trial
      of steroids is worthwhile.

PMID- 29662576
TI  - Chronically Discharging Ears: Evalution with High Resolution Computed Tomography.
AB  - Chronic suppurative otitis media (CSOM) refers to the middle ear inflammation
      which is clinically characterized by the discharging ear, hearing deficit, fever
      and otalgia. Although a clinical diagnosis, imaging is imperative to rule out
      associated complications which apart from causing hearing deficit, may prove
      fatal at times. Both high resolution computed tomography (HRCT) and MRI are
      helpful in evaluating middle ear pathologies, usage being indication specific.
      Due to its excellent spatial resolution, HRCT is invaluable in assessment of
      chronically discharging ears, especially to look for bone erosion and the
      integrity of the ossicles. Due to its better spatial resolution, HRCT is
      preferred in suspected intra temporal complications whereas MRI is more useful in
      evaluating intracranial extension.

PMID- 29662577
TI  - Fahr Syndrome - an Important Piece of a Puzzle in the Differential Diagnosis of
      Many Diseases.
AB  - Fahr syndrome is a rare neurodegenerative disorder characterized by symmetrical,
      bilateral calcifications in the basal ganglia, nucleus gyrus and cerebral cortex.
      The continuous advancement as well as widespread use of brain imaging have
      contributed to the increasing detection rates of such changes. Nevertheless,
      their etiology is understood only partially and the methods of causative
      treatment are limited. Due to various symptoms, Fahr syndrome may resemble
      diseases from the field of neurology, psychiatry, cardiology and even urology.
      This article provides an up-to-date review of the literature concerning Fahr
      syndrome in terms of clinical practice.

PMID- 29662578
TI  - Endovascular Embolization of Renal Cell Carcinoma in a Patient with Solitary
      Kidney.
AB  - Background: Kidney tumors account for about 3% of tumors in adults. The primary
      therapy of renal cancer is the surgical removal. Traditionally, and also modern
      procedures are performed to remove the kidneys, especially when the tumor
      involves the entire kidney. In the cases of unresectable tumors embolization is
      used as a palliative procedure. Case Report: The aim of this study is to present
      the case of endovascular treatment of renal cell carcinoma in patient with
      solitary kidney. 77-years old patient had an ultrasound examination because of
      the pain in left lumbar region. MRI confirmed the presence of tumor size 29*45 mm
      in the left kidney. The right kidney had been removed eight years earlier because
      of clear cell carcinoma. Histopathological diagnosis was renal clear cell
      carinoma. The patient did not consent to surgical treatment. Tumor embolization
      was proceeded as a minimally invasive procedure. Pathological tumor vessels were
      closed using particles filling the entire vascular tumor. Next, the blood vessels
      supplying the tumor were closed using a mixture of lipiodolu and glubranu.
      Control angiographiy of the left renal artery confirmed the effective closure of
      all vascular pathology. In a recent ultrasound examination which was done 15
      months after surgery no evidence of vascular pathology was found. Conclusions:
      Embolization of kidney cancer in particular cases may be an alternative way of
      treatment and give a good result in the form of stopping the growth of the tumor
      with simultaneous retaining the remaining parenchyma and renal function.

PMID- 29662579
TI  - Cardiac Magnetic Resonance Imaging Using an Open 1.0T MR Platform: A Comparative
      Study with a 1.5T Tunnel System.
AB  - Background: Cardiac magnetic resonance imaging (cMRI) has become the non-invasive
      reference standard for the evaluation of cardiac function and viability. The
      introduction of open, high-field, 1.0T (HFO) MR scanners offers advantages for
      examinations of obese, claustrophobic and paediatric patients.The aim of our
      study was to compare standard cMRI sequences from an HFO scanner and those from a
      cylindrical, 1.5T MR system. Material/Method: Fifteen volunteers underwent cMRI
      both in an open HFO and in a cylindrical MR system. The protocol consisted of
      cine and unenhanced tissue sequences. The signal-to-noise ratio (SNR) for each
      sequence and blood-myocardium contrast for the cine sequences were assessed.
      Image quality and artefacts were rated. The location and number of non-diagnostic
      segments was determined. Volunteers' tolerance to examinations in both scanners
      was investigated. Results: SNR was significantly lower in the HFO scanner (all
      p<0.001). However, the contrast of the cine sequence was significantly higher in
      the HFO platform compared to the 1.5T MR scanner (0.685+/-0.41 vs. 0.611+/-0.54;
      p<0.001). Image quality was comparable for all sequences (all p>0.05). Overall,
      only few non-diagnostic myocardial segments were recorded: 6/960 (0.6%) by the
      HFO and 17/960 (1.8%) segments by the cylindrical system. The volunteers
      expressed a preference for the open MR system (p<0.01). Conclusions: Standard
      cardiac MRI sequences in an HFO platform offer a high image quality that is
      comparable to the quality of images acquired in a cylindrical 1.5T MR scanner. An
      open scanner design may potentially improve tolerance of cardiac MRI and
      therefore allow to examine an even broader patient spectrum.

PMID- 29662580
TI  - Application of Intravoxel Incoherent Motion (IVIM) Model for Differentiation
      Between Metastatic and Non-Metastatic Head and Neck Lymph Nodes.
AB  - Background: Application of intravoxel incoherent motion (IVIM) model parameters,
      including: true diffusion (D), pseudodiffusion (D*), and perfusion fraction (Fp),
      for differentiation between metastatic and non-metastatic head and neck lymph
      nodes. Material/Methods: Diffusion-weighted images/apparent diffusion coefficient
      (DWI/ADC) images of 86 lymph nodes from 31 cancer patients were analyzed. DWI
      images were obtained with a 1.5T MRI scanner (Magnetom Avanto); b=0,50, 150, 300,
      500, 750, 1000, 1200 s/mm2. Results: In the study group, there were 32 (37%) and
      54 (67%) metastatic and non-metastatic lymph nodes, respectively. The mean values
      of D, D*, and Fp did not differ significantly between metastatic and non
      metastatic lymph nodes. Conclusions: IVIM parameters are not useful for
      differentiation between metastatic and non-metastatic head and neck lymph nodes.

PMID- 29662581
TI  - Evaluating Qualitative and Quantitative Computerized Tomography Indicators of
      Chronic Obstructive Pulmonary Disease and Their Correlation with Pulmonary
      Function Tests.
AB  - Background: With increasingly aging populations, chronic obstructive pulmonary
      disease (COPD) is the fourth leading cause of death today. Emphysematous changes,
      an important component of the disease, must be determined on HRCT, either
      qualitatively or quantitatively. The purpose of this study was to evaluate
      features that help determine emphysematous changes and correlate them with
      respiratory function tests (RFTs). Material/Methods: A total of thirty COPD
      patients and a control group of the same size, matched for age, were included in
      the study. The mean lung parenchyma density values on inspiration and expiration,
      visual HRCT scores, and pulmonary function tests were obtained. IBM SPSS
      statistical software (version 22) was used to perform correlation analysis
      (Pearson's coefficient) and the Mann-Whitney U test. Results: The most valuable
      RFTs for determining emphysematous changes were DLCO, FEV1, and FEV1/FVC, in that
      order. Quantitative measures of the mean lung density had the highest correlation
      with coefficient on expiration. Conclusions: As regards the comparison between
      objective and subjective density values, the HRCT-based visual density values are
      satisfactory. On the other hand, the best assessment can be performed with the
      use of mean density values on expiration. DLCO, FEV1, and FEV1/FVC were found to
      be valuable parameters in determining parenchymal changes.

PMID- 29662582
TI  - Multi Detector Computed Tomography Fistulography In Patients of Fistula-in-Ano:
      An Imaging Collage.
AB  - Fistula-in-ano, or perianal fistula, is a challenging clinical condition for both
      diagnosis and treatment. Imaging modalities such as fistulography, anal
      endosonography, perineal sonography, magnetic resonance imaging (MRI), and
      computed tomography (CT) are available for its evaluation. MRI is considered as
      the modality of choice for an accurate delineation of the tract in relation to
      the sphincter complex and for the detection of associated complications. However,
      its availability and affordability is always an issue. Moreover, the requirement
      to obtain multiple sequences to depict the fistula in detail is cumbersome and
      confusing for the clinicians to interpret. The inability to show the fistula in
      relation to normal anatomical structures in a single image is also a limitation.
      Multi detector computed tomography fistulography (MDCTF) is an underutilized
      technique for defining perianal fistulas. Acquisition of iso-volumetric data sets
      with instillation of contrast into the fistula delineates the tract and its
      components. Post-processing with thin sections allows for a generation of good
      quality images for presentation in various planes (multi-planar reconstructions)
      and formats (volume rendered technique, maximum intensity projection). MDCTF
      demonstrates the type of fistula, its extent, whether it is simple or complex,
      and shows the site of internal opening and associated complications; all in easy
      to understand images that can be used by the surgeons. Its capability to
      represent the entire pathology in relation to normal anatomical structures in few
      images is a definite advantage. MDCTF can be utilized when MRI is contraindicated
      or not feasible. This pictorial review shares our initial experience with MDCT
      fistulography in evaluating fistula-in-ano, demonstrates various components of
      fistulas, and discusses the types of fistulas according to the standard Parks
      classification.

PMID- 29662583
TI  - Sonographic Appearance of Testicular Adrenal Rest Tumour in a Patient with
      Congenital Adrenal Hyperplasia.
AB  - Background: Testicular adrenal rest tumours (TARTs) are benign testicular masses
      that are found in inadequately treated patients with congenital adrenal
      hyperplasia (CAH). Recognizing this association and identifying characteristic
      ultrasound features of TARTs is important so as to avoid misdiagnosing them as
      malignancies, which can lead to unnecessary interventions. Case Report: We
      describe a case of a 9-year-old boy, with a diagnosis of CAH and precocious
      puberty, who was referred to our department for an ultrasound evaluation of the
      abdomen and scrotum. On ultrasound, there were well-defined, heterogeneous,
      predominantly hypoechoic, round-to-oval masses in both testes. Taking into
      account the presence of CAH and a typical sonographic appearance of bilateral
      testicular masses, a diagnosis of testicular adrenal rest tumour was made; biopsy
      was deferred and hormonal treatment was modified. Conclusions: Prompt diagnosis
      of testicular adrenal rest tumours is essential, as it only indicates inadequate
      hormonal control. Moreover, it can prevent unnecessary biopsies and
      orchidectomies, and can maintain fertility. TARTs have a typical imaging
      appearance that every radiologist must be aware of.

PMID- 29662584
TI  - Cerebral Metastases of Lung Cancer Mimicking Multiple Ischaemic Lesions - A Case
      Report and Review of Literature.
AB  - Background: Restricted diffusion that is found on magnetic resonance diffusion
      weighted imaging (DWI) typically indicates acute ischaemic stroke. However,
      restricted diffusion can also occur in other diseases, like metastatic brain
      tumours, which we describe in this case report. Case Report: A 57-year-old male,
      with a diagnosis of small-cell cancer of the right lung (microcellular anaplastic
      carcinoma), was admitted with focal neurological symptoms. Initial brain MRI
      revealed multiple, disseminated lesions that were hyperintense on T2-weighted
      images and did not enhance after contrast administration; notably, some lesions
      manifested restricted diffusion on DWI images. Based on these findings,
      disseminated ischaemic lesions were diagnosed. On follow-up MRI that was
      performed after 2 weeks, we observed enlargement of the lesions; there were
      multiple, disseminated, sharply outlined, contrast-enhancing, oval foci with
      persistent restriction of diffusion. We diagnosed the lesions as disseminated
      brain metastases due to lung cancer. To our knowledge, this is the first
      description of a patient with brain metastases that were characterised by
      restricted diffusion and no contrast enhancement. Conclusions: Multiple,
      disseminated brain lesions, that are characterised by restricted diffusion on
      DWI, typically indicate acute or hyperacute ischemic infarcts; however, they can
      also be due to hypercellular metastases, even if no contrast enhancement is
      observed. This latter possibility should be considered particularly in patients
      with cancer.

PMID- 29662585
TI  - Role of Diffusion-Weighted Magnetic Resonance (MR) Imaging in Differentiation
      Between Graves' Disease and Painless Thyroiditis.
AB  - Background: To assess the role of diffusion-weighted MR imaging in
      differentiation between Graves' disease and painless thyroiditis.
      Material/Methods: A prospective study was conducted among 37 consecutive patients
      with untreated thyrotoxicosis (25 female and 12 male; mean age of 44 years) and
      15 ageand sex-matched controls. Diffusion-weighted MR imaging of the thyroid
      gland was performed in patients and controls. The apparent diffusion coefficient
      (ADC) value of the thyroid gland was calculated and correlated with Tc-99m uptake
      and thyroid function tests of the patients. Results: There was a significant
      difference in the ADC value of the thyroid gland between patients and the control
      group (P=0.001). The mean ADC value of the thyroid gland in Graves' disease was
      2.03+/-0.28*10-3 mm2/sec, and in patients with painless thyroiditis 1.46+/
      0.22*10-3 mm2/sec, respectively. There was a significant difference in the ADC
      values between Graves' disease and painless thyroiditis (P=0.001). When the ADC
      value of 1.45*10-3 mm2/sec was used as a threshold value for differentiating
      Graves' disease from painless thyroiditis, the best result was obtained with area
      under the curve of 0.934, accuracy of 83.8%, sensitivity of 95.8%, and
      specificity of 61.5%. The mean ADC value of the thyroid gland in patients
      positively correlated with serum TRAb and Tc-99m uptake (r=0.57, P=0.001 and
      r=0.74, P=0.001, respectively). Conclusions: We concluded that ADC values of the
      thyroid gland can be used to differentiate Graves' disease from painless
      thyroiditis in patients with untreated thyrotoxicosis.

PMID- 29662586
TI  - Structural Variations in Parotid Glands Induced by Radiation Therapy in Patients
      with Oral Carcinoma Observed on Contrast-Enhanced Computed Tomography.
AB  - Background: Xerostomia is one of the commonest radiation-induced complications in
      patients with head and neck carcinoma. The aim of this study was to assess
      structural variations in parotid glands induced by radiation therapy in patients
      with oral carcinoma with contras-enhanced computed tomography (CECT).
      Material/Methods: A retrospective study was performed in 41 patients with oral
      carcinoma who underwent CECT for head and neck malignancies before and after
      radiotherapy. We analyzed the relationship between parotid density variations,
      parotid volume change, as seen on CECT, and the mean radiation dose applied to
      the parotid glands in patients with oral carcinoma immediately after
      radiotherapy, and 2 and 3 years later. Results: Immediately after radiotherapy,
      high-density changes on contrast-enhanced CT were observed in 70.5% of the
      irradiated parotids. Low-density changes due to fat degeneration were seen in
      46.2% and 72.2% of the irradiated parotids 2 and 3 years after radiotherapy,
      respectively. The mean dose applied to the parotids with the low-density changes
      and without such changes 3 years after radiotherapy was 46.0 Gy and 27.7 Gy,
      respectively (p=0.049). Furthermore, parotid shrinkage was observed in 63.6% of
      the irradiated parotids. Conclusions: This study suggests that the structural
      variations in parotid glands induced by radiotherapy included high-density
      changes that were observed immediately after radiotherapy and low-density changes
      that were seen at late follow-up. This study should be useful for clinicians in
      the assessment of radiation-induced injuries in the parotids with respect to
      early prediction of xerostomia.

PMID- 29662587
TI  - Impact of Window Computed Tomography (CT) Parameters on Measurement of
      Inflammatory Changes in Paranasal Sinuses.
AB  - Background: In accordance with the European guidelines on rhinosinusitis and
      nasal polyps (EPOS 2012), CT is used as the main imaging modality for the
      assessment intensity of inflammatory lesions.The aim of this study was to measure
      the differences in the assessment of inflammatory changes in the paranasal
      sinuses due to different parameters of width (W) and length (L) of the CT window.
      Material/Methods: A retrospective analysis included 44 CT scans of the paranasal
      sinuses that were performed in adults. All studies were characterized by the
      presence of inflammatory changes in at least one of the sinuses.Measurements of
      the same inflammatory lesions were performed sequentially with different CT
      windows. The results were statistically analyzed. Results: A statistically
      significant difference was observed between the average measurements that were
      performed with the use CT windows dedicated for the sinuses and head. A downward
      trend in the measured values and a shift towards soft tissue values was observed
      with decreasing window parameters. Conclusions: A major cause of inaccurate
      examinations of pathological changes in the paranasal sinuses may be due to
      selection of unsuitable CT windows. Therefore, in order to avoid missing
      inflammatory lesions in the paranasal sinuses, it is reasonable to use CT windows
      dedicated for the sinuses or bones.

PMID- 29662588
TI  - Imaging Diagnosis of Chronic Encapsulated Intracerebral Hematoma, a Comparison of
      Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) characteristics.
AB  - Background: Chronic encapsulated intracerebral hematoma (CEICH) is a rare type of
      intracerebral hematoma that is often misdiagnosed.To explore the characteristics
      of CEICH on computerized tomography (CT) and magnetic resonance imaging (MRI).
      Material/Methods: Clinical, CT, MRI, and susceptibility weighted imaging (SWI)
      data of 5 patients who were diagnosed with CEICH on surgery and pathology were
      retrospectively analyzed. Results: CT showed quasi-circular or elliptical lesions
      with clear borders in all 5 cases and iso-density or low-density in the center of
      lesions that were surrounded by peripheral edema in 2 cases. CT showed mass
      effect in 5 patients. On contrast-enhanced CT, 2 cases exhibited mild ring
      enhancement, and 3 cases exhibited moderate ring enhancement. MRI showed cystic
      lesions with high uniform signal on T1-weighted images (T1WI) and T2-weighted
      images (T2WI), a lowsignal ring sign on the coated cystic lesions on T2WI, a
      lower signal ring sign on SWI, and ring enhancement after administration of
      contrast. Conclusions: CT imaging of CEICH did not reveal any typical
      characteristics in the studied patients. MRI showed an envelope with a "ring" and
      intra-capsular bleeding features. MRI is an effective imaging modality for the
      diagnosis of CEICH.

PMID- 29662589
TI  - Sonography and Magnetic Resonance Imaging Characteristics of Testicular Adrenal
      Rest Tumors.
AB  - Background: The aim of this study was to describe the gray-scale and color
      Doppler ultrasonography (US) and magnetic resonance (MR) imaging features of
      testicular adrenal rest tumors (TART) in patients with congenital adrenal
      hyperplasia. Material/Methods: Forty-one patients with congenital adrenal
      hyperplasia were evaluated by gray-scale and color Doppler ultrasonography.
      Totally eighteen adrenal rest tumors in 9 patients were diagnosed TART on US and
      MR imaging. Gray-scale and color Doppler US and MR findings of the patients were
      documented. Results: A total of eighteen masses were evaluated in nine patients.
      The mean age of these patients was 14.3+/-4.5 (range 10.1-23.3) years. US
      revealed hypoechoic lesions around the mediastinum testis with hypervascularity
      dispersing in ten patients and hypovascularity in two patients. In six patients,
      the lesions were hyperechoic with poor vascularity. Lesions exhibited homogeneous
      (n=8) and heterogeneous (n=10). Testicular microlithiasis was present in 4 of 9
      patients with TART. Doppler ultrasound showed normal testicular vessels passing
      through the mass which were undisturbed, not displaced and not change in caliber.
      MRI features were the following: all lesions were hypointense on T2- and
      hyperintense (n=12) and isointense (n=6) on T1-weighted images. All masses
      revealed homogeneous contrast enhancement on postcontrast T1-weighted images.
      Conclusions: Ultrasonography and MRI are good methods for detecting and
      monitoring TART. US is the first preferable modality because it is quick and
      cheap than MRI. Bilateral mostly hypoechoic lesions depicted around the
      mediastinum testis with no mass effect is highly suggestive for the diagnosis of
      testicular adrenal rest tissues on ultrasonography. Normal testicular vessels
      coursing through the lesions undisturbed and not change in caliber is described
      specific for this kind of tumors.

PMID- 29662590
TI  - Computed Tomography (CT) Angiography in Pre-Embolization Assessment of Location
      of Gastrointestinal Bleeding in Paediatric Patient with Granulomatosis with
      Polyangiitis (Wegener's Granulomatosis) - Case Report.
AB  - Background: Acute gastrointestinal bleeding is an emergency with a high morbidity
      and mortality. Early diagnosis and appropriate intervention can be lifesaving and
      can prevent long-term complications. Case Report: In this case report, we discuss
      and illustrate the role of CT angiography in the evaluation of acute, active
      gastrointestinal haemorrhage and show its usefulness prior to embolization. We
      describe a 15-year-old girl with granulomatosis with polyangiitis, formerly known
      as Wegener's granulomatosis. Conclusions: An accurate pre-embolization assessment
      of bleeding with CT angiography shortens the total diagnostic time, which results
      in prompt and more effective endovascular treatment.We describe the clinical
      presentation of our patient and present diagnostic and interventional radiologic
      findings.

PMID- 29662591
TI  - Impact of Allura Clarity Technology on Radiation Dose Exposure During Left Atrial
      Appendage Closure.
AB  - Background: To evaluate the impact of the Clarity IQ technology on reducing
      radiation risk in patients undergoing cardiac interventional radiology (IR)
      procedures. Material/Methods: Phantom studies were performed with two
      angiographic systems, FD10 Allura Xper and FD10 Allura Clarity. In the study, we
      performed left atrial appendage closure. Dosimetric measurements were performed
      with thermoluminescent dosimeters (TLD) placed inside a CIRS anthropomorphic
      phantom. Radiation risk was estimated based on the TLD readings and expressed as
      the dose absorbed by particular organs. The Mann-Whitney U test was carried out
      to test for significance of differences in the absorbed radiation doses between
      the techniques. Results: During left atrial appendage closure, the estimated dose
      absorbed by particular organs was lower in the case of the FD10 Allura Clarity
      system in comparison to the Allura Xper. In this procedure, dose reduction for
      particular organs ranged between 49-86%. Conclusions: Application of the FD10
      Allura Clarity system resulted in a significant dose reduction, thereby leading
      to a significant decrease in radiation risk for patients undergoing IR
      procedures.

PMID- 29662592
TI  - Radiation Dose Associated with Multi-Detector 64-Slice Computed Tomography Brain
      Examinations in Khartoum State, Sudan.
AB  - Background: Radiation exposure due to computed tomography (CT) has become an
      important issue, as the number of CT examinations has been increasing worldwide.
      Radiation doses associated with CT are higher in comparison to other imaging
      procedures. CT-related radiation doses should be monitored and controlled in
      order to ensure reduction of radiation exposure and optimization of image
      quality. The aim of this study was to evaluate radiation doses in adult patient
      who underwent routine CT brain examinations, and to assess how CT scanning
      protocols affect patient doses in practice. Material/Methods: A total of 118
      patients underwent brain CT at two radiology departments equipped with 64-slice
      CT scanners, Khartoum, Sudan. Patient doses regarding weighted CT dose index
      (CTDIw) and dose length product (DLP) values were recorded. Quality control tests
      were performed for both scanners. Results: The mean CTDIw values ranged from 62.9
      to 65.8 mGy, DLP values ranged from 1003.7 to 1192.5 mGy, and the effective dose
      varied from 2.4 to 3.7 mSv. Conclusions: Patient doses in this study was higher
      compared to previous research, suggesting that patients exposed to unnecessary
      radiation. Therefore, optimization of radiation doses with the use of specified
      imaging protocols, well-documented indications for CT, training of technicians,
      and quality control programs will reduce the necessary radiation doses.
      Establishment of the diagnostic reference level is recommended for further dose
      reduction.

PMID- 29662593
TI  - Clival Chordoma: Case Report and Review of Recent Developments in Surgical and
      Adjuvant Treatments.
AB  - Chordomas are rare tumors that can develop anywhere along the craniospinal axis.
      These tumors present challenges with respect to diagnosis and treatment due to a
      high rate of recurrence, even after multiple surgeries, and the propensity to
      involve any region within the craniospinal axis. New developments in radiation
      therapy have improved recurrence-free survival in patients with chordomas.
      Different regimens of chemotherapy and molecularly-targeted therapies, as
      adjuvants to surgery, have been described in individual case reports and case
      series. The purpose of this paper is to describe a case of clival chordoma and
      review recent developments in diagnostic and therapeutic options. A 77-year-old
      female was referred because of diplopia and progressively worsening headaches.
      Head imaging revealed a large expansile and erosive mass in the skull base. The
      patient underwent a successful endoscopic endonasal trans-sphenoidal resection of
      the mass, with biopsy confirming the diagnosis of chordoma. Postoperatively, the
      patient experienced an improvement in neurological symptoms. Chordomas can
      present a diagnostic challenge due to the rare occurrence and a tendency to
      involve any region within the craniospinal axis.

PMID- 29662594
TI  - Correlation Between Findings of Multislice Helical Computed Tomography (CT),
      Endoscopic Examinations, Endovascular Procedures, and Surgery in Patients with
      Symptoms of Acute Gastrointestinal Bleeding.
AB  - Background: Endoscopic methods (gastroscopy and colonoscopy) are considered
      fundamental for the diagnosis of gastrointestinal bleeding. In recent years,
      multidetector computed tomography (MDCT) has also gained importance in diagnosing
      gastrointestinal bleeding, particularly in hemodynamically unstable patients and
      in cases with suspected lower gastrointestinal tract bleeding. CT can detect both
      the source and the cause of active gastrointestinal bleeding, thereby expediting
      treatment initiation. Material/Methods: The study group consisted of 16 patients
      with clinical symptoms of gastrointestinal bleeding in whom features of active
      bleeding were observed on CT. In all patients, bleeding was verified by means of
      other methods such as endoscopic examinations, endovascular procedures, or
      surgery. Results: The bleeding source was identified on CT in all 16 patients. In
      14 cases (87.5%), bleeding was confirmed by other methods. Conclusions: CT is an
      efficient, fast, and readily available tool for detecting the location of acute
      gastrointestinal bleeding.

PMID- 29662595
TI  - Diagnosis of Acute Appendicitis Using Clinical Alvarado Scoring System and
      Computed Tomography (CT) Criteria in Patients Attending Gujarat Adani Institute
      of Medical Science - A Retrospective Study.
AB  - Background: The aim was to evaluate the clinical Alvarado scoring system and
      computed tomography (CT) criteria for the diagnosis of acute appendicitis.
      Material/Methods: The study was carried out retrospectively in patients who were
      referred to the Institute between March 2014 and January 2015. One hundred
      seventeen patients with acute abdominal pain who underwent abdominal CT were
      enrolled in this retrospective study. Patient demographics, clinical Alvarado
      scoring, CT images, and pathologic results of the patients were evaluated.
      Results: Thirty nine of the 53 patients who were operated on had pathologically
      proven acute appendicitis. CT criteria of appendiceal diameter, presence of
      periappendiceal inflammation, fluid, appendicoliths, and white blood cell count
      (WBC) were significantly correlated with the inflammation of the appendix. The
      optimal cut-off value of the appendiceal diameter was 6.5 mm. The correlation
      between appendiceal diameter and WBC was 80% (P=0.01 <0.05). The correlation
      between appendiceal diameter and Alvarado score was 78.7% (P=0.01 <0.05).
      Conclusions: Presence of appendiceal diameter above 6.5 mm on CT, periappendiceal
      inflammation, fluid, and appendicoliths should prompt the diagnosis of acute
      appendicitis. Since patients with acute appendicitis may not always show the
      typical signs and symptoms, CT is a helpful imaging modality for patients with
      relatively low Alvarado scores and leukocytosis, when physical examination is
      confusing.

PMID- 29662596
TI  - Single Nanoparticle Plasmonic Spectroscopy for Study of Charge-Dependent Efflux
      Function of Multidrug ABC Transporters of Single Live Bacillus subtilis Cells.
AB  - Multidrug membrane transporters can selectively extrude a wide variety of
      structurally and functionally unrelated substrates, and they are responsible for
      ineffective treatment of a wide range of diseases (e.g., infection and cancer).
      Their underlying molecular mechanisms remain elusive. In this study, we
      functionalized Ag NPs (11 nm in diameter) with two biocompatible peptides
      (CALNNK, CALNNE) to prepare positively and negatively charged Ag-peptide NPs (Ag
      CALNNK NPs+zeta, Ag-CALNNE NPs-4zeta), respectively. We used them as photostable
      plasmonic imaging probes to study charge-dependent efflux kinetics of BmrA (ABC)
      membrane transporter of single live Bacillus (B.) subtilis cells. Two strains of
      the cells, normal expression of BmrA (WT) or devoid of BmrA (DeltaBmrA), were
      used to study the charge-dependent efflux kinetics of single NPs upon the
      expression of BmrA. The NPs (1.4 nM) were stable (non-aggregated) in a PBS buffer
      and biocompatible to the cells. We found the high dependent accumulation of the
      intracellular NPs in both WT and DeltaBmrA upon the charge and concentration of
      NPs. Notably, the accumulation rates of the positively charged NPs in single live
      WT cells are nearly identical to those in DeltaBmrA cells, showing independence
      upon the expression of BmrA. In contrast, the accumulation rates of the
      negatively charged NPs in WT are much lower than in DeltaBmrA, showing high
      dependence upon the expression of BmrA and suggesting that BmrA extrude the
      negatively charged NPs, but not positively charged NPs, out of the WT. The
      accumulation of positively charged NPs in both WT and DeltaBmrA increases nearly
      proportionally to the NP concentration. The accumulation of negatively charged
      NPs in DeltaBmrA, but not in WT, also increases nearly proportionally to the NP
      concentration. These results suggest that both negatively and positively charged
      NPs enter the cells via passive diffusion driven by concentration gradients
      across the cellular membrane, and BmrA can only extrude the negatively charged
      NPs out of the WT. This study shows that single NP plasmon spectroscopy can serve
      as a powerful tool to identify single plasmonic NPs and to probe the charge
      dependent efflux kinetics and function of single membrane transporters in single
      live cells in real time.

PMID- 29662597
TI  - Acromegaly and hyperparthyroidism: about a rare association.

PMID- 29662598
TI  - [Clinical, epidemiological and therapeutic features of biliary tract cancers:
      about 20 cases].
AB  - Biliary tract cancers mainly occur in two sites: gallbladder cancer which are
      adenocarcinomas and intra- and extrahepatic cholangiocarcinomas. We conducted a
      retrospective study of 20 cases with biliary tract cancer in the Department of
      Surgery at the General Hospital in Grand-Yoff between January 2006 and October
      2014. 40% of patients had gallbladder cancer, 60% of patients had common bile
      duct cancer. Sex ratio was 1. The average age of patients was 58.1 years. The
      average time to diagnosis was 3.77 months. Symptomatology was dominated by
      icteric syndrome and right hypochondrium pain. All patients had biological
      manifestation of cholestatic syndrome. Abdominal ultrasound was performed in 65%
      of patients, while abdominal CT scan in 85% of cases and MRI in 35% of cases.
      Advanced cancers were predominant in our case series (n=19). The majority of
      patients underwent palliative surgery. The most practiced treatment was biliary
      diversion (50% of patients). There was a predominance of cholangiocarcinomas. The
      overall operative morbidity rate was 43.75%. The overall mortality rate in our
      patients with biliary tract cancers of any site was 31.25%. Median survival was 4
      months and a half. Biliary tract cancers have multifaceted features and can be
      differentiated essentially among intrahepatic cholangiocarcinoma, extrahepatic
      cholangiocarcinoma, gallbladder adenocarcinoma whose evolution is globally
      different but the prognosis is spontaneously poor.

PMID- 29662599
TI  - [Spontaneous simultaneous bilateral rupture of the quadriceps tendon in patients
      with parathyroid adenoma: case report and literature review].
AB  - Spontaneous as well as bilateral and simultaneous rupture of the quadriceps
      tendon is rare. We report the case of a 53-year old patient followed up for
      parathyroid adenoma complicated by renal failure, admitted for spontaneous
      bilateral rupture of the two quadriceps tendons. He underwent surgical repair
      allowing him to maintain his autonomy.

PMID- 29662600
TI  - [Appendicular plastron: emergency or deferred surgery: a series of 27 cases
      collected in the surgical clinic of the Aristide Le Dantec Hospital].
AB  - Our study aimed to evaluate the outcome of the surgical treatment of appendicular
      plastron after deferred or emergency appendectomy. We conducted a retrospective,
      descriptive study of 27 patients treated for appendicular plastron from January
      2000 to 31 December 2007. Diagnosis was based on clinical examination showing a
      mass in the right iliac fossa, on ultrasound or made intraoperatively. All
      patients undergoing emergency surgery were classified in Group I while those
      undergoing deferred surgery were classified in Group II. 18 men and 9 women were
      registered, with a sex-ratio man /Woman=2. The average age of patients was 33
      years, ranging between 19 and 57 years. Clinical signs were dominated by pain in
      the right iliac fossa and fever in 25(92.6%) and 15 (55.6%) of cases
      respectively. In group I, appendectomy couldn't be performed in 7 cases (n= 15)
      due to surgical complications. In all other cases appendectomy was performed by
      enlarging Mac Burney's incision and was associated with longer length of stay in
      hospital. Group II included 12 patients (n=12), 9 underwent laparoscopy and 3
      patients underwent Mac Burney's incision. 3 cases with peritoneal adhesions were
      detected during coelioscopy. Deferred appendectomy of appendicular plastron is a
      safe and efficient surgical procedure. It allows to avoid unattractive scarrings
      and iatrogenic digestive fistulas. Emergency appendectomy shouldn't be performed
      in patients with appendicular plastron because it increases the risks of
      morbidity.

PMID- 29662601
TI  - Indometacin induced corneal perforation in a patient with rheumatoid arthritis.

PMID- 29662602
TI  - Adult aorta coarctation associated with double superior vena cava.

PMID- 29662603
TI  - Increased mortality among HIV infected patients with cryptococcal antigenemia in
      Guinea-Bissau.
AB  - Cryptococcal antigenemia may precede development of cryptococcal meningitis and
      death among patients with advanced HIV infection. Among 200 retrospectively and
      randomly selected ART-naive patients with CD4 counts < 100 cells/MUl from Guinea
      Bissau, 20 (10%) had a positive cryptococcal antigen test. Self-reported headache
      and fever were predictors of a positive test, while cryptococcal antigenemia was
      a strong predictor of death within the first year of follow-up, MRR 2.22 (95% CI:
      1.15-4.30). Screening for cryptococcal antigenemia should be implemented for
      patients with advanced HIV in Guinea-Bissau. Pre-emptive anti-fungal therapy
      should be initiated prior to ART-initiation if the screening is positive.

PMID- 29662604
TI  - ?
AB  - This study aims to determine the frequency and identify the factors associated
      with undernutrition among patients undergoing visceral surgery in 2014. We
      conducted a cross-sectional, descriptive and analytical study over the period
      September 11, 2014-December 11, 2014. The study population comprised patients who
      had undergone visceral surgery at the National University Hospital Centre
      Koutoucou Hubert MAGA, Cotonou. Undernutrition is defined as a body mass index
      less than 18.5 kg/m2. A total of 90 patients were included in the study, 57,78%
      (52 patients) were male. The average age of patients was 55+/-6,32 years.
      Undernutrition was found in 42 patients (46.67%). The factors associated with
      undernutrition in postoperative patients were: age greater than or equal to 50
      years, low level of protein, water and energy intake, diarrhea, cancer, digestive
      system surgery, emergency surgery, significant weight loss and hyperleukocytosis.
      Undernutrition is common in postoperative patients. Hence the importance of
      nutritional screening and of early treatment.

PMID- 29662605
TI  - ?

PMID- 29662606
TI  - ?
AB  - Introduction Aim: It was to determine the factors influencing the prognosis of
      the second twin's delivery. Methods: The study was retrospective and covered all
      cases of twin births registered at our maternity from 1stJanuary 2007 to 31st
      December 2016 (10 years). Results: We recorded 34,899 deliveries among which 1374
      twin deliveries (2.54%). Almost 15% were primiparous; 39.16% were referred;
      69.10% and 15.5% without prenatal care. The factors negatively influencing
      prognosis for second twin were: a delay>15 minutes between twin deliveries,
      delayed caesarean section, non-qualification of the midwife, monochoreal, low
      birth weight. Otherwise parity and obstetric maneuvers had no influence on the
      prognosis 2nd twin. Conclusion: The prognosis of 2nd twinisstronglyinfluenced by
      a birth delay> 15 minutes, the other factors acting as cofactors.

PMID- 29662607
TI  - ?
AB  - Endometriosis is defined as the implantation of endometrial tissue outside of the
      uterine cavity. It affects approximately 10% of women of childbearing age.
      Umbilical endometriosis is rare and its pathophysiology is poorly known. We
      report the case of a 42-year old nulliparous female patient with a 5-year history
      of myomectomy, presenting with cyclic pain associated with umbilical mass. The
      diagnosis of umbilical endometrioma was made and confirmed by the histological
      examination of the surgical specimen. Treatment was based on wide excision of the
      mass associated with pelvis exploration and umbilical plasty.

PMID- 29662608
TI  - WT1, p53 and p16 expression in the diagnosis of low- and high-grade serous
      ovarian carcinomas and their relation to prognosis.
AB  - Objective: To evaluate the diagnostic and prognostic value of the
      immunohistochemical expression of WT1, p53 and p16 in low- (LGSOCs) and high
      grade serous ovarian carcinomas (HGSOCs). Results: HGSOC had a significantly
      higher proportion of advanced stage disease, higher CA125 levels, higher
      proportion of post-surgery residual disease and higher recurrence or disease
      progression. WT1 was expressed in 71.4% of LGSOCs and in 57.1% of HGSOCs (p =
      0.32). Focal and/or complete absence of p53 expression with negative p16
      expression was found in 90.5% of LGSOCs, in contrast to the 88.1% of HGSOCs with
      diffuse or complete absence of p53 expression with positive p16 expression
      (<0.001). The IHC p53/p16 index and the morphological classification were closely
      matched (k = 0.68). In the univariate analysis, FIGO stage, post-surgery residual
      disease and histological grade were significantly associated with progression
      free survival (PFS) and overall survival (OS). The IHC p53/p16 index was
      associated only with PFS. WT1 was not associated with PFS or OS. According to the
      multivariate analysis, advanced FIGO stage and presence of post-surgery residual
      disease remained independent prognostic factors for worst PFS, however these
      features had only a trend association with OS. Methods: 21 LGSOC and 85 HGSOC
      stage I-IV cases were included. The morphological classification was assessed
      according to the World Health Organization (WHO) criteria. Immunohistochemistry
      (IHC) was performed in tissue microarray slides. IHC p53/p16 index was compared
      with the morphological classification. Conclusions: The IHC p53/p16 index was a
      good marker for the differentiation of LGSOC and HGSOC, but the morphologic
      classification showed a better association with survival. FIGO stage and post
      surgery residual disease remained the only independent prognostic factors for
      survival.

PMID- 29662609
TI  - DEC205 mediates local and systemic immune responses to Helicobacter pylori
      infection in humans.
AB  - Helicobacter pylori infections cause gastritis and affect systemic immune
      responses; however, no direct association between immune cells and stomach
      bacteria has yet been reported. The present study investigated DEC205-mediated
      phagocytosis of H. pylori and the role of DEC205-positive macrophages in the
      human gastric mucosa. DEC205 mediated phagocytosis of H. pylori was detected
      immunocytochemically in PMA-stimulated macrophages differentiated from NOMO1
      cells. Expression of DEC205 mRNA in peripheral blood mononuclear cells (PBMCs)
      from H. pylori-infected patients was analyzed following stimulation with H.
      pylori cell lysate. We found that anti-DEC205 antibodies inhibited phagocytosis
      of H. pylori. The number of cells double-positive for DEC205 and CD14 in human
      gastric mucosa was higher in H. pylori-infected patients. DEC205-positive
      macrophages invaded the extracellular space between epithelial cells within
      gastric pits. In addition, DEC205 mRNA expression was upregulated in human PBMCs
      stimulated with H. pylori lysate. These findings suggest DEC205-expressing
      macrophages are important for recognition of H. pylori in human gastric mucosa,
      which affects systemic immunity.

PMID- 29662610
TI  - Human cancer cells utilize mitotic DNA synthesis to resist replication stress at
      telomeres regardless of their telomere maintenance mechanism.
AB  - Telomeres resemble common fragile sites (CFSs) in that they are difficult-to
      replicate and exhibit fragility in mitosis in response to DNA replication stress.
      At CFSs, this fragility is associated with a delay in the completion of DNA
      replication until early mitosis, whereupon cells are proposed to switch to a
      RAD52-dependent form of break-induced replication. Here, we show that this
      mitotic DNA synthesis (MiDAS) is also a feature of human telomeres. Telomeric
      MiDAS is not restricted to those telomeres displaying overt fragility, and is a
      feature of a wide range of cell lines irrespective of whether their telomeres are
      maintained by telomerase or by the alternative lengthening of telomeres (ALT)
      mechanism. MiDAS at telomeres requires RAD52, and is mechanistically similar to
      CFS-associated MiDAS, with the notable exception that telomeric MiDAS does not
      require the MUS81-EME1 endonuclease. We propose a model whereby replication
      stress initiates a RAD52-dependent form of break-induced replication that
      bypasses a requirement for MUS81-EME1 to complete DNA synthesis in mitosis.

PMID- 29662611
TI  - GPX2 promotes development of bladder cancer with squamous cell differentiation
      through the control of apoptosis.
AB  - Herein, we elucidated the molecular mechanisms and therapeutic potential of
      glutathione peroxidase 2 (GPX2) in bladder cancer. GPX2 expression gradually
      increased during progression from normal to papillary or nodular hyperplasia
      (PNHP) and urothelial carcinoma (UC) in a rat N-butyl-N-(4-hydroxybutyl)
      nitrosamine (BBN)-induced bladder carcinogenesis model. GPX2 overexpression was
      more marked in UC with squamous differentiation (SqD) than in pure UC. Clinical
      intraepithelial lesions of papillary UC and invasive UC with SqD also had strong
      GPX2 expression in human radical cystectomy specimens. In addition, prognostic
      analysis using transurethral specimens revealed that low expression level of GPX2
      predicted poor prognosis in patients with pure UC. Further, UC cell lines, BC31
      and RT4, cultured in vitro also overexpressed GPX2. Knock-down of GPX2 induced
      significant inhibition of intracellular reactive oxygen species (ROS) production,
      in addition to significant growth inhibition and increased apoptosis with
      activation of caspase 3 or 7 in both BC31 and RT4 cells. Interestingly, tumor
      growth of BC31 cells subcutaneously transplanted in nude mice was significantly
      caused the induction of apoptosis, as well as inhibition of angiogenesis and SqD
      by GPX2 down-regulation. Our findings demonstrated that GPX2 plays an important
      role in bladder carcinogenesis through the regulation of apoptosis against
      intracellular ROS, and may be considered as a novel biomarker or therapeutic
      target in bladder cancer.

PMID- 29662612
TI  - Exploiting mitochondrial and metabolic homeostasis as a vulnerability in NF1
      deficient cells.
AB  - Neurofibromatosis type 1 is a disease caused by mutation of neurofibromin 1
      (NF1), loss of which results in hyperactive Ras signaling and a concomitant
      increase in cell proliferation and survival. Patients with neurofibromatosis type
      1 frequently develop tumors such as plexiform neurofibromas and malignant
      peripheral nerve sheath tumors. Mutation of NF1 or loss of the NF1 protein is
      also observed in glioblastoma, lung adenocarcinoma, and ovarian cancer among
      other sporadic cancers. A therapy that selectively targets NF1 deficient tumors
      would substantially advance our ability to treat these malignancies. To address
      the need for these therapeutics, we developed and conducted a synthetic lethality
      screen to discover molecules that target yeast lacking the homolog of NF1, IRA2.
      One of the lead candidates that was observed to be synthetic lethal with
      ira2Delta yeast is Y100. Here, we describe the mechanisms by which Y100 targets
      ira2Delta yeast and NF1-deficient tumor cells. Y100 treatment disrupted
      proteostasis, metabolic homeostasis, and induced the formation of mitochondrial
      superoxide in NF1-deficient cancer cells. Previous studies also indicate that
      NF1/Ras-dysregulated tumors may be sensitive to modulators of oxidative and ER
      stress. We hypothesize that the use of Y100 and molecules with related mechanisms
      of action represent a feasible therapeutic strategy for targeting NF1 deficient
      cells.

PMID- 29662613
TI  - Efficacy of continuous versus intermittent subglottic secretion drainage in
      preventing ventilator-associated pneumonia in patients requiring mechanical
      ventilation: A single-center randomized controlled trial.
AB  - Objective: Aspiration of subglottic secretion is a widely used intervention to
      prevent ventilator-associated pneumonia (VAP). This study aimed to compare the
      efficacy of continuous and intermittent subglottic secretion drainage (SSD) in
      preventing VAP. Methods: A single-center randomized controlled trial was
      conducted on adult postoperative patients who were expected to undergo mechanical
      ventilation for more than 48 hours. Primary outcome measure was incidence of VAP
      and secondary outcome measures were length of mechanical ventilation and
      intensive-care unit (ICU) stay. Results: Fifty-nine patients received continuous
      SSD, while 60 patients received intermittent SSD. Of these 119 patients, 88 (74%)
      were excluded and 15 and 16 patients were allocated to receive continuous and
      intermittent SSD, respectively. VAP was detected in 4 (26.7%) and 7 (43.8%)
      patients in the continuous and intermittent groups, respectively, (p=0.320). The
      length of mechanical ventilation was significantly shorter (p=0.034) in the
      continuous group (99.5+/-47.1 h) than in the intermittent group (159.9+/-94.5 h).
      The length of ICU stay was also shorter (p=0.0097) in the continuous group (6.3+/
      2.1 days) than the intermittent group (9.8+/-4.8 days). Conclusions: Although
      continuous SSD did not reduce the incidence of VAP, it reduced the length of
      mechanical ventilation and ICU stay when compared to intermittent SSD.

PMID- 29662614
TI  - Transcriptional orchestration of mitochondrial homeostasis in a cellular model of
      PGC-1-related coactivator-dependent thyroid tumor.
AB  - The PGC-1 (Peroxisome proliferator-activated receptor Gamma Coactivator-1) family
      of coactivators (PGC-1alpha, PGC-1beta, and PRC) plays a central role in the
      transcriptional control of mitochondrial biogenesis and oxidative phosphorylation
      (OXPHOS) processes. These coactivators integrate mitochondrial energy production
      into cell metabolism using complementary pathways. The XTC.UC1 cell line is a
      mitochondria-rich model of thyroid tumors whose biogenesis is almost exclusively
      dependent on PRC. Here we aim to propose an integrative view of the cellular
      pathways regulated by PRC through integration of cDNA and miRNA microarray data
      and chromatin immunoprecipitation results obtained from XTC.UC1 cells invalidated
      for PRC. This study showes that PRC induces a complex network of cellular
      functions interacting with at least one to five of the studied transcription
      factors (Estrogen Related Receptor alpha, ERR1; Nuclear-Respiratory Factors, NRF1
      and NRF2; cAMP Response Element Binding, CREB; and Ying Yang, YY1). Our data
      confirm that ERR1 is a key partner of PRC in the regulation of mitochondrial
      functions and suggest a potential role of this complex in RNA processing. PRC is
      also involved in transcriptional regulatory complexes targeting 12 miRNAs, five
      of which are involved in the control of the OXPHOS process. Our findings
      demonstrate that the PRC coactivator can act in complex with several
      transcription factors and regulate miRNA expression to control the fine
      regulation of main metabolic functions in the cell. Therefore, in PGC-1alpha/beta
      associated pathologies, PRC, as a metabolic sensor, may ensure mitochondrial
      homeostasis.

PMID- 29662615
TI  - Transcriptome and proteome profiling reveals stress-induced expression signatures
      of imiquimod-treated Tasmanian devil facial tumor disease (DFTD) cells.
AB  - As a topical cancer immunotherapy, the toll-like receptor 7 ligand imiquimod
      activates tumor regression via stimulation of immune cell infiltration and
      cytotoxic responses. Imiquimod also exerts direct pro-apoptotic effects on tumor
      cells in vitro, but a role for these effects in imiquimod-induced tumor
      regression remains undefined. We previously demonstrated that cell lines derived
      from devil facial tumor disease (DFTD), a transmissible cancer threatening the
      survival of the Tasmanian devil (Sarcophilus harrisii), are sensitive to
      imiquimod-induced apoptosis. In this study, the pro-apoptotic effects of
      imiquimod in DFTD have been investigated using RNA-sequencing and label-free
      quantitative proteomics. This analysis revealed that changes to gene and protein
      expression in imiquimod treated DFTD cells are consistent with the onset of
      oxidative and endoplasmic reticulum stress responses, and subsequent activation
      of the unfolded protein response, autophagy, cell cycle arrest and apoptosis.
      Imiquimod also regulates the expression of oncogenic pathways, providing a direct
      mechanism by which this drug may increase tumor susceptibility to immune
      cytotoxicity in vivo. Our study has provided the first global analysis of
      imiquimod-induced effects in any tumor cell line. These findings have highlighted
      the potential of cell stress pathways as therapeutic targets in DFTD, and will
      allow for improved mechanistic use of imiquimod as a therapy in both the
      Tasmanian devil and human cancers.

PMID- 29662616
TI  - Recruitment of lysine demethylase 2A to DNA double strand breaks and its
      interaction with 53BP1 ensures genome stability.
AB  - Lysine demethylase 2A (KDM2A) functions in transcription as a demethylase of
      lysine 36 on histone H3. Herein, we characterise a role for KDM2A in the DNA
      damage response in which KDM2A stimulates conjugation of ubiquitin to 53BP1.
      Impaired KDM2A-mediated ubiquitination negatively affects the recruitment of
      53BP1 to DSBs. Notably, we show that KDM2A itself is recruited to DSBs in a
      process that depends on its demethylase activity and zinc finger domain.
      Moreover, we show that KDM2A plays an important role in ensuring genomic
      stability upon DNA damage. Depletion of KDM2A or disruption of its zinc finger
      domain results in the accumulation of micronuclei following ionizing radiation
      (IR) treatment. In addition, IR-treated cells depleted of KDM2A display premature
      exit from the G2/M checkpoint. Interestingly, loss of the zinc finger domain also
      resulted in 53BP1 focal distribution in condensed mitotic chromosomes. Overall,
      our data indicates that KDM2A plays an important role in modulating the
      recruitment of 53BP1 to DNA breaks and is crucial for the preservation of genome
      integrity following DNA damage.

PMID- 29662617
TI  - Premature ovarian aging in BRCA carriers: a prototype of systemic precocious
      aging?
AB  - Purpose: Though former evidence implies a correlation of breast cancer
      susceptibility gene (BRCA) mutation with reduced ovarian reserve, the data is yet
      inconsistent. Our aim was to investigate biomarkers of ovarian aging in a cohort
      of young healthy carriers of the BRCA mutation. We hypothesized that the role
      played by BRCA genes in aging pathways is not exclusive to the ovary.
      Experimental Design: Healthy female BRCA carriers, 40 years or younger and
      healthy male BRCA carriers, 50 years or younger, were enrolled in the study.
      Serum anti-mullerian Hormone (AMH), fibroblast growth factor-23 (FGF-23), Klotho
      and IL-1 were measured by enzyme-linked immunosorbent assay (ELISA). Ovarian AMH
      and protein kinase B (AKT) mRNA from BRCA carriers who underwent prophylactic
      oophorectomy and from age-matched, healthy, non-carriers who underwent partial
      oophorectomy due to benign conditions were analyzed by qPCR. Results: Thirty
      three female (median age 35y) and 20 male (44y) BRCA carriers were enrolled into
      the study and matched to control non-carriers (34y and 43y, respectively). Serum
      AMH level was significantly lower in BRCA female carriers than in both non
      carrier controls and age-matched nomograms. The levels of ovarian AMH and AKT
      mRNA were significantly lower in carriers than in controls. The systemic aging
      cytokines FGF-23, klotho and IL-1 displayed a differential expression in carriers
      of both genders. FGF-23 level was higher in carriers (P=0.06). Conclusions: Our
      results suggest a link between BRCA mutation, accelerated ovarian aging and
      systemic aging-related pathophysiology.

PMID- 29662618
TI  - Ectopic expression of transcription factor BATF3 induces B-cell lymphomas in a
      murine B-cell transplantation model.
AB  - The mechanisms involved in malignant transformation of mature B and T lymphocytes
      are still poorly understood. In a previous study, we compared gene expression
      profiles of the tumor cells of Hodgkin lymphoma (HL) and anaplastic large cell
      lymphoma (ALCL) to their normal cellular counterparts and found the basic leucine
      zipper protein ATF-like 3 (BATF3) to be significantly upregulated in the tumor
      cells of both entities. To assess the oncogenic potential of BATF3 in
      lymphomagenesis and to dissect the molecular interactions of BATF3 in lymphoma
      cells, we retrovirally transduced murine mature T and B cells with a BATF3
      encoding viral vector and transplanted each population into Rag1-deficient
      recipients. Intriguingly, BATF3-expressing B lymphocytes readily induced B-cell
      lymphomas after characteristic latencies, whereas T-cell transplanted animals
      remained healthy throughout the observation time. Further analyses revealed a
      germinal center B-cell-like phenotype of most BATF3-initiated lymphomas. In a
      multiple myeloma cell line, BATF3 inhibited BLIMP1 expression, potentially
      illuminating an oncogenic action of BATF3 in B-cell lymphomagenesis. In
      conclusion, BATF3 overexpression induces malignant transformation of mature B
      cells and might serve as a potential target in B-cell lymphoma treatment.

PMID- 29662619
TI  - Uev1A-Ubc13 promotes colorectal cancer metastasis through regulating CXCL1
      expression via NF-kB activation.
AB  - Colorectal cancer is the second most common cause of cancer-related death
      worldwide. Uncontrolled growth and distant metastasis are hallmarks of colorectal
      cancer. However, the precise etiological factors and the mechanisms are diverse
      and still largely unclear. The potential proto-oncogene UEV1A encodes a ubiquitin
      conjugating enzyme variant, which is required for Ubc13-catalyzed K63-linked poly
      ubiquitination of target proteins and the activation of NF-kB, a transcription
      factor known to be involved in innate immunity, anti-apoptosis, inflammation and
      cancer. In order to understand the roles of Uev1A in colon cancer progression, we
      experimentally manipulated the Uev1A level in HCT116 colon cancer cells and found
      that UEV1A overexpression alone is sufficient to promote invasion in vitro and
      metastasis in vivo. This process is mediated by NF-kappaB activation and depends
      on its physical interaction with Ubc13. No expression of Uev1A was detected in
      histologically normal human colonic mucosa, but its expression was detected in
      human colorectal adenocarcinoma, which was closely correlated with nuclear p65
      levels, an indicator of NF-kappaB activation. Uev1A protein was detected in 46%
      of primary tumors and 79% of metastatic tumors examined. Our experimental data
      establish that among NF-kappaB target genes, Uev1A-regulated CXCL1 expression
      plays a critical role in colon cell invasion and metastasis, a notion supported
      by the colon adenocarcinoma survey. Furthermore, experimental depletion of Uev1
      in HCT116 cells reduces CXCL1 expression, and prevents cell invasion and tumor
      growth in a xenograft mouse model. These results identify Uev1A as a potential
      therapeutic target in the treatment of metastatic colorectal cancers.

PMID- 29662620
TI  - Promotion of malignant phenotype after disruption of the three-dimensional
      structure of cultured spheroids from colorectal cancer.
AB  - Individual and small clusters of cancer cells may detach from the edges of a main
      tumor and invade vessels, which can act as the origin of metastasis; however, the
      mechanism for this phenomenon is not well understood. Using cancer tissue
      originated spheroids, we studied whether disturbing the 3D architecture of cancer
      spheroids can provoke the reformation process and progression of malignancy. We
      developed a mechanical disruption method to achieve homogenous disruption of the
      spheroids while maintaining cell-cell contact. After the disruption, 9 spheroid
      lines from 9 patient samples reformed within a few hours, and 3 of the 9 lines
      exhibited accelerated spheroid growth. Marker expression, spheroid forming
      capacity, and tumorigenesis indicated that stemness increased after spheroid
      disruption. In addition, the spheroid forming capacity increased in 6 of 11
      spheroid lines. The disruption signature determined by gene expression profiling
      supported the incidence of remodeling and predicted the prognosis of patients
      with colorectal cancer. Furthermore, WNT and HER3 signaling were increased in the
      reformed spheroids, and suppression of these signaling pathways attenuated the
      increased proliferation and stemness after the disruption. Overall, the
      disruption and subsequent reformation of cancer spheroids promoted malignancy
      related phenotypes through the activation of the WNT and ERBB pathways.

PMID- 29662621
TI  - The role and gene expression profile of SOCS3 in colorectal carcinoma.
AB  - SOCS3 has been postulated to play a role in the occurrence and progression of
      malignancies. However, the relationship of SOCS3 with colorectal carcinoma
      remains poorly understood. The purpose of the study was to explore the role of
      SOCS3 in colorectal carcinoma and its underlying mechanisms. Protein and mRNA
      expression of SOCS3 in colorectal carcinoma and normal colorectal mucosa was
      detected using immunohistochemistry and real-time quantitative PCR. SOCS3
      expression was significantly lower in colorectal carcinoma tissue than in normal
      colorectal mucosa, and was negatively correlated with tumor invasion depth, lymph
      node metastasis, differentiation degree, and TNM stage. A stably transfected
      colorectal carcinoma cell line (8348SOCS3) with high expression of SOCS3 was
      established. The effects of SOCS3 overexpression on the growth, proliferation,
      invasion and tumor formation of colorectal carcinoma cells were examined by CCK-8
      assay, transwell method and tumorigenicity assays in nude mice. Then we found
      SOCS3 overexpression significantly decreased proliferation and invasion
      capability of 8348 cells in vitro and in vivo. Furthermore, the effect of SOCS3
      overexpression on the gene expression profile of colorectal carcinoma cells was
      analyzed using human genome arrays. The results revealed 369 genes that were
      differentially expressed in 8348SOCS3 cells. 193 genes was significantly
      increased and 176 genes was significantly decreased. Bioinformatics analysis
      demonstrated that high SOCS3 expression affected multiple signaling pathways in
      colorectal carcinoma including TGF-beta/Smads, NF-kappaB, and HIF-MAPK pathways.
      Especially for the TGF-beta/Smads pathways, high SOCS3 expression could inhibit
      TGF-beta1 expression and activate Smad4 expression. These data suggested that low
      expression of SOCS3 was associated with the occurrence and progression of
      colorectal carcinoma. SOCS3 protein may be a useful indicator for malignancy and
      prognosis of colorectal carcinoma and also a new target for gene therapy.

PMID- 29662622
TI  - Quantitative parameters in dynamic contrast-enhanced magnetic resonance imaging
      for the detection and characterization of prostate cancer.
AB  - Objectives: to assess the diagnostic accuracy of quantitative parameters of DCE
      MRI in multi-parametric MRI (mpMRI) in comparison to the histopathology
      (including Gleason grade) of prostate cancer. Patients and methods: 150 men with
      suspected prostate cancer (abnormal digital rectum examination and or elevated
      prostate-specific antigen) received pre-biopsy 3T mpMRI and were recruited into
      peer-reviewed, protocol-based prospective study. The DCE-MRI quantitative
      parameters (Ktrans (influx transfer constant) and kep (efflux rate constant)) of
      the cancerous and normal areas were recorded using four different kinetic models
      employing Olea Sphere (Olea Medical, La Ciotat, France). The correlation between
      these parameters and the histopathology of the lesions (biopsy and in a sub
      cohort 41 radical prostatectomy specimen) was assessed. Results: The quantitative
      parameters showed a significant difference between non-cancerous (benign) and
      cancerous lesions (Gleason score>=3+3) in the prostate gland. The cut-off values
      for prostate cancer differentiation were: Ktrans (0.205 min-1) and kep (0.665 min
      1) in the extended Tofts model (ET) and Ktrans (0.205 min-1 and kep (0.63 min-1)
      in the Lawrence and Lee delay (LD) models respectively. The mean Ktrans value
      also showed a difference between low-grade cancer (Gleason score=3+3) and high
      grade cancer (Gleason score >= 3+4). With the addition of DCE-MRI quantitative
      parameters, the sensitivity of the PIRAD scoring system was increased from 56.6%
      to 92.1% (Ktrans _ET), 93.1% (kep _ET), 91.0%, (Ktrans _LD) and 89.4% (kep _LD).
      Conclusion: Quantitative DCE-MRI parameters improved the diagnostic performance
      of conventional MRI in distinguishing normal and prostate cancers, including
      characterization of grade of cancers. The ET and LD models in post-image
      processing analysis provided better cut-off values for prostate cancer
      differentiation than the other quantitative DCE-MRI parameters.

PMID- 29662623
TI  - Cancer reversion with oocyte extracts is mediated by cell cycle arrest and
      induction of tumour dormancy.
AB  - Inducing stable control of tumour growth by tumour reversion is an alternative
      approach to cancer treatment when eradication of the disease cannot be achieved.
      The process requires re-establishment of normal control mechanisms that are lost
      in cancer cells so that abnormal proliferation can be halted. Embryonic
      environments can reset cellular programmes and we previously showed that axolotl
      oocyte extracts can reprogram breast cancer cells and reverse their
      tumorigenicity. In this study, we analysed the gene expression profiles of oocyte
      extract-treated tumour xenografts to show that tumour reprogramming involves cell
      cycle arrest and acquisition of a quiescent state. Tumour dormancy is associated
      with increased P27 expression, restoration of RB function and downregulation of
      mitogen-activated signalling pathways. We also show that the quiescent state is
      associated with increased levels of H4K20me3 and decreased H4K20me1, an
      epigenetic profile leading to chromatin compaction. The epigenetic reprogramming
      induced by oocyte extracts is required for RB hypophosphorylation and induction
      of P27 expression, both occurring during exposure to the extracts and stably
      maintained in reprogrammed tumour xenografts. Therefore, this study demonstrates
      the value of oocyte molecules for inducing tumour reversion and for the
      development of new chemoquiescence-based therapies.

PMID- 29662624
TI  - Arsenic trioxide-mediated suppression of miR-182-5p is associated with potent
      anti-oxidant effects through up-regulation of SESN2.
AB  - Arsenic trioxide (ATO) is a traditional Chinese medicine that can induce
      oxidative stress for treatment of cancer cells. However, ATO may generate anti
      oxidative responses to compromise the cytotoxic effect, but the underlying
      mechanisms remain unclear. Here we found that ATO could inhibit miR-182-5p
      expression in patient-derived primary S1 glioblastoma (GBM) cells accompanied by
      up-regulation of Sestrin-2 (SESN2) mRNA, a known anti-oxidant molecule. This
      phenomenon was also detected in a U87MG glioma cell line, human lung
      adenocarcinoma H1299 cell line and A549 cell line. Pretreatment with a free
      radical scavenger N-acetylcysteine (NAC) reduced the oxidative stress induced by
      ATO. Concomitantly, ATO mediated suppression of miR-182-5p and enhancement of
      SESN2 expression were also compromised. The MTT assay further showed that ATO
      induced cytotoxicity was enhanced by transfection of miR-182-5p mimics.
      Overexpression of miR-182-5p mimics significantly suppressed the expression of
      SENS2 and a firefly luciferase reporter gene fused to 3'- untranslated region
      (UTR) of SESN2 mRNA. Use of ribonucleoprotein immunoprecipitation (RNP-IP), ATO
      mediated suppression of miR-182-5p led to the stabilization of SESN2 mRNA as a
      result of Argonaute-2 (AGO2) dependent gene silencing. Furthermore, high
      expression of miR-182-5p and low expression of SESN2 mRNA tend to be associated
      with longer survival of glioma or lung cancer patients using public available
      gene expression datasets and online tools for prediction of clinical outcomes.
      Taken together, current data suggest that the miR-182-5p/SENS2 pathway is
      involved in ATO induced anti-oxidant responses, which may be important for the
      design of novel strategy for cancer treatment.

PMID- 29662625
TI  - ADAM17 inhibition enhances platinum efficiency in ovarian cancer.
AB  - Chemotherapeutic resistance evolves in about 70 % of ovarian cancer patients and
      is a major cause of death in this tumor entity. Novel approaches to overcome
      these therapeutic limitations are therefore highly warranted. A disintegrin and
      metalloprotease 17 (ADAM17) is highly expressed in ovarian cancer and required
      for releasing epidermal growth factor receptor (EGFR) ligands like amphiregulin
      (AREG). This factor has recently been detected in ascites of advanced stage
      ovarian cancer patients. However, it is not well understood, whether and how
      ADAM17 might contribute to chemo resistance of ovarian cancer. In this study, we
      identified ADAM17 as an essential upstream regulator of AREG release under
      chemotherapeutic treatment in ovarian cancer cell lines and patient derived
      cells. In the majority of ovarian cancer cells cisplatin treatment resulted in
      enhanced ADAM17 activity, as shown by an increased shedding of AREG. Moreover,
      both mRNA and the protein content of AREG were dose-dependently increased by
      cisplatin exposure. Consequently, cisplatin strongly induced phosphorylation of
      ADAM17-downstream mediators, the EGFR and extracellular signal-regulated kinases
      (ERK). Phorbol 12-myristate 13-acetate (PMA), similarly to cisplatin, mediated
      AREG shedding and membrane fading of surface ADAM17. Inhibition of ADAM17 with
      either GW280264X or the anti-ADAM17 antibody D1 (A12) as well as silencing of
      ADAM17 by siRNA selectively reduced AREG release. Thus, ADAM17 inhibition
      sensitized cancer cells to cisplatin-induced apoptosis, and significantly reduced
      cell viability. Based on these findings, we propose that targeting of ADAM17 in
      parallel to chemotherapeutic treatment suppresses survival pathways and
      potentially diminish evolving secondary chemo resistance mechanisms.

PMID- 29662626
TI  - Store operated calcium entry is altered by the inhibition of receptors tyrosine
      kinase.
AB  - SOCE (Store-Operated Calcium Entry) is the main mechanism by which external Ca2+
      enters into non-excitable cells after endoplasmic reticulum emptying. It is
      implicated in several processes such as proliferation and migration. Alterations
      in SOCE could initiate or support the development of hallmarks of cancer. In this
      project, we showed that disruption of the EGFR/ErbB2-dependent signalling by
      lapatinib and CP-724714, two inhibitors of the receptor tyrosine kinase (RTK),
      dramatically reduced the amplitude of the SOCE in breast cancer cells. LY294002
      and MK2206, two inhibitors of the PI3K/Akt pathway, mimicked the effect of the
      inhibition of EGFR/ErbB2. In contrast, inhibitors of the MAPK pathway had no
      effect on SOCE. The involvement of EGFR/ErbB2 receptors and the PI3K/Akt pathway
      in the regulation of SOCE was confirmed in other cell lines derived from various
      cancer types. All these results showed that SOCE is positively regulated by the
      PI3K/Akt pathway and that this effect may be suppressed by the inhibition of the
      upstream RTKs. Inhibition of SOCE might therefore contribute to the anticancer
      effects of RTK inhibitors.

PMID- 29662627
TI  - Analysis of the PI3K-AKT-mTOR pathway in penile cancer: evaluation of a
      therapeutically targetable pathway.
AB  - Objectives: To determine whether phosphatidylinositol-4,5-bisphosphate 3- kinase,
      catalytic subunit alpha (PIK3CA) copy number gain is common and could prove a
      useful marker for the activation status of the PI3K-AKT-mTOR pathway in penile
      squamous cell carcinoma (PSCC). Methods: Fresh frozen tissue and archival blocks
      were collected from 24 PSCC patients with 15 matched normal penile epithelium
      (NPE) tissue from St George's Hospital. PIK3CA mutational and copy number status
      (CNS) was assessed via Sanger sequencing and fluorescence in-situ hybridisation,
      respectively. PIK3CA RNA expression was quantified using TaqMan gene expression
      assay. HPV DNA was detected with INNO-LiPA assay. p-AKT and p-mTOR protein
      expression were assessed using western blot and immunohistochemistry. Results:
      PIK3CA copy number gain was found in 11/23 (48%) patients, with mutations present
      in only 2/24 (8%) patients. In comparison to NPE, PSCC showed significantly lower
      PIK3CA RNA expression (p=0.0007), p-AKT (Ser473) nuclear immunoexpression
      (p=0.026) and protein expression of p-AKT (Thr308) (p=0.0247) and p-mTOR
      (Ser2448) (p=0.0041). No association was found between PIK3CA CNS and p-AKT and p
      mTOR protein expression. Conclusion: Based on our results the PI3K-AKT-mTOR
      pathway is not a key driver in PSCC carcinogenesis and the therapeutic targeting
      of this pathway is unlikely to produce significant clinical benefit.

PMID- 29662628
TI  - A gene expression signature predicts recurrence-free survival in meningioma.
AB  - BACKGROUND: Meningioma is the most common primary brain tumor and has a variable
      risk of local recurrence. While World Health Organization (WHO) grade generally
      correlates with recurrence, there is substantial within-grade variation of
      recurrence risk. Current risk stratification does not accurately predict which
      patients are likely to benefit from adjuvant radiation therapy (RT). We
      hypothesized that tumors at risk for recurrence have unique gene expression
      profiles (GEP) that could better select patients for adjuvant RT. METHODS: We
      developed a recurrence predictor by machine learning modeling using a
      training/validation approach. RESULTS: Three publicly available AffymetrixU133
      gene expression datasets (GSE9438, GSE16581, GSE43290) combining 127 primary, non
      treated meningiomas of all grades served as the training set. Unsupervised
      variable selection was used to identify an 18-gene GEP model (18-GEP) that
      separated recurrences. This model was validated on 62 primary, non-treated cases
      with similar grade and clinical variable distribution as the training set. When
      applied to the validation set, 18-GEP separated recurrences with a
      misclassification error rate of 0.25 (log-rank p=0.0003). 18-GEP was predictive
      for tumor recurrence [p=0.0008, HR=4.61, 95%CI=1.89-11.23)] and was predictive
      after adjustment for WHO grade, mitotic index, sex, tumor location, and Simpson
      grade [p=0.0311, HR=9.28, 95%CI=(1.22-70.29)]. The expression signature included
      genes encoding proteins involved in normal embryonic development, cell
      proliferation, tumor growth and invasion (FGF9, SEMA3C, EDNRA), angiogenesis
      (angiopoietin-2), cell cycle regulation (CDKN1A), membrane signaling (tetraspanin
      7, caveolin-2), WNT-pathway inhibitors (DKK3), complement system (C1QA) and
      neurotransmitter regulation (SLC1A3, Secretogranin-II). CONCLUSIONS: 18-GEP
      accurately stratifies patients with meningioma by recurrence risk having the
      potential to guide the use of adjuvant RT.

PMID- 29662629
TI  - Pre-diagnostic biomarkers of metabolic dysregulation and cancer mortality.
AB  - INTRODUCTION: The obesogenic milieu is a pro-tumorigenic environment that
      promotes tumor initiation, angiogenesis and metastasis. In this prospective
      cohort, we examined the association between pre-diagnostic metabolic biomarkers,
      plasma adiponectin, resistin, leptin and lipoprotein (a), and the risk of cancer
      mortality. METHODS: Prospective data was obtained from the REasons for Geographic
      and Racial Differences in Stroke (REGARDS) cohort of Blacks and Whites followed
      from 2003 through 2012 for cancer mortality. We determined the association
      between metabolism biomarkers (log-transformed and tertiles) and risk of cancer
      mortality using Cox Proportional Hazards models with robust sandwich estimators
      to calculate the 95% confidence intervals (CIs), and adjusted for baseline
      covariates, including age, gender, income, education, physical activity, BMI,
      smoking status, alcohol use, and comorbidity score. RESULTS: Among 1764
      participants with available biomarker data, each SD higher log-leptin was
      associated with a 54% reduced risk of total cancer mortality (HR: 0.46, 95% CI:
      0.23 - 0.92) and obesity-related cancer mortality (HR: 0.55, 95% CI: 0.39-0.79).
      Among Blacks only, each SD higher log-resistin was associated with a nearly 7
      fold increased risk of cancer mortality (adjusted HR: 6.68, 95% CI: 2.10 -
      21.21). There were no significant associations of adiponectin or Lp(a) and cancer
      mortality. CONCLUSIONS: Leptin is involved in long-term regulation of energy
      balance, while resistin is involved in chronic inflammation and LDL production.
      These findings highlight the biological mechanisms linking metabolic
      dysregulation with cancer mortality, and the influence of resistin on cancer
      mortality only among Blacks suggests that this hormone may be a useful biomarker
      of racial differences in cancer mortality that deserves further study. IMPACT:
      Our observed increased risk of cancer mortality associated with higher serum
      resistin levels among Blacks suggests that if validated in larger cohorts,
      clinical strategies focused on resistin control may be a promising cancer
      prevention strategy.

PMID- 29662630
TI  - Type II RAF inhibitor causes superior ERK pathway suppression compared to type I
      RAF inhibitor in cells expressing different BRAF mutant types recurrently found
      in lung cancer.
AB  - A large fraction of somatic driver BRAF mutations in lung cancer are non-V600 and
      impaired-kinase. Non-V600 BRAF mutations predict sensitivity to combination of a
      type I RAF inhibitor, Dabrafenib, and a MEK inhibitor, Trametinib. Singly,
      Dabrafenib only weakly suppresses mutant BRAF-induced ERK signaling and can
      induce ERK paradoxical activation in CRAF-overexpressing cells. The present study
      compared the effects of Dabrafenib and a type II RAF inhibitor, AZ628, on ERK
      activity in HEK293T cells expressing several tumor-derived BRAF mutants, and in a
      non-V600 and impaired-kinase BRAF-mutant lung cancer cell line (H1666). Unlike
      Dabrafenib, AZ628 did not induce paradoxical ERK activation in CRAF
      overexpressing cells and BRAF-mutant cells overexpressing CRAF were more
      responsive to AZ628 compared to Dabrafenib in terms of ERK inhibition. AZ628
      inhibited ERK more effectively than Dabrafenib in both H1666 cells and HEK293T
      cells co-expressing several different BRAF-mutants with CRAF. Similarly, AZ628
      plus Trametinib had better MEK-inhibitory and pro-apoptotic effects in H1666
      cells than Dabrafenib plus Trametinib. Moreover, prolonged treatment of H1666
      cells with AZ628 plus Trametinib produced greater inhibition of cell growth than
      Dabrafenib plus Trametinib. These results indicate that AZ628 has greater
      potential than Dabrafenib, both as a single agent and combined with Trametinib,
      for the treatment of non-V600 BRAF mutant lung cancer.

PMID- 29662631
TI  - Overlap at the molecular and immunohistochemical levels between
      angioimmunoblastic T-cell lymphoma and a subgroup of peripheral T-cell lymphomas
      without specific morphological features.
AB  - The overlap of morphology and immunophenotype between angioimmunoblastic T-cell
      lymphoma (AITL) and other nodal peripheral T-cell lymphomas (n-PTCLs) is a matter
      of current interest whose clinical relevance and pathogenic background have not
      been fully established. We studied a series of 98 n-PTCL samples (comprising 57
      AITL and 41 PTCL-NOS) with five TFH antibodies (CD10, BCL-6, PD-1, CXCL13, ICOS),
      looked for mutations in five of the genes most frequently mutated in AITL (TET2,
      DNMT3A, IDH2, RHOA and PLCG1) using the Next-Generation-Sequencing Ion Torrent
      platform, and measured the correlations of these characteristics with morphology
      and clinical features. The percentage of mutations in the RHOA and TET2 genes was
      similar (23.5% of cases). PLCG1 was mutated in 14.3%, IDH2 in 11.2% and DNMT3A in
      7.1% of cases, respectively. In the complete series, mutations in RHOA gene were
      associated with the presence of mutations in IDH2, TET2 and DNMT3A (p < 0.001, p
      = 0.043, and p = 0.029, respectively). Fourteen cases featured RHOA mutations
      without TET2 mutations. A close relationship was found between the presence of
      these mutations and a TFH-phenotype in AITL and PTCL-NOS patients. Interestingly,
      BCL-6 expression was the only TFH marker differentially expressed between AITL
      and PTCL-NOS cases. There were many fewer mutated cases than there were cases
      with a TFH phenotype. Overall, these data suggest alternative ways by which
      neoplastic T-cells overexpress these proteins. On the other hand, no clinical or
      survival differences were found between any of the recognized subgroups of
      patients with respect to their immunohistochemistry or mutational profile.

PMID- 29662632
TI  - Regulation of breast cancer induced bone disease by cancer-specific IKKbeta.
AB  - NFkappaB is implicated in breast cancer bone metastasis and skeletal remodelling.
      However, the role of IKKbeta, a key component of the canonical NFkappaB pathway,
      in the regulation of breast cancer osteolytic metastasis has not been
      investigated. Here, we describe the cancer-specific contribution of IKKbeta to
      bone metastasis, skeletal tumour growth and osteolysis associated with breast
      cancer. IKKbeta is highly expressed in invasive breast tumours and its level of
      expression was higher in patients with bone metastasis. IKKbeta overexpression in
      parental MDA-MD-231 breast cancer cells, promoted mammary tumour growth but
      failed to convey osteolytic potential to these cells in mice. In contrast,
      IKKbeta overexpression in osteotropic sub-clones of MDA-MB-231 cells with
      differing osteolytic phenotypes increased incidence of bone metastasis,
      exacerbated osteolysis and enhanced skeletal tumour growth, whereas its knockdown
      was inhibitory. Functional and mechanistic studies revealed that IKKbeta enhanced
      the ability of osteotropic MDA-MB-231 cells to migrate, increase
      osteoclastogenesis, and to inhibit osteoblast differentiation via a mechanism
      mediated, at least in part, by cytoplasmic sequestering of FoxO3a and VEGFA
      production. Thus, tumour-selective manipulation of IKKbeta and its interaction
      with FoxO3a may represent a novel strategy to reduce the development of secondary
      breast cancer in the skeleton.

PMID- 29662633
TI  - Tracking cellular and molecular changes in a species-specific manner during
      experimental tumor progression in vivo.
AB  - Hepatoblastoma (HBL) is a pediatric liver cancer with defined molecular
      alterations driving its progression. Here, we describe an animal model for HBL on
      the chick chorioallantoic membrane (CAM), which recapitulates relevant features
      of HBL in patients. Expression of classic tumor-associated proteins such as beta
      catenin, EpCAM and CK19 was maintained in acini-like organized tumors on CAM, as
      was synthesis of AFP, a tumor marker used for monitoring patient response. RNA
      sequencing revealed an unexpected molecular evolution of HBL cells on the CAM,
      with significant deregulation of more than 6,000 genes including more than half
      of all HOX genes. Bioinformatic analysis distinguish between tumor cell-expressed
      genes and chick genes, thereby shedding new light on the complex interactions
      taking place during HBL progression. Importantly, human tumor suppressive
      ribosomal genes were downregulated after implantation, whereas mitochondrial
      genes encoding for anti-apoptotic peptides were strongly induced in vivo. Meprin
      1alpha expression was increased during evolution of CAM tumors and confirmed by
      immunohistochemistry. Cisplatin, a commonly used chemotherapeutic agent for HBL,
      showed significant anti-tumoral effects. Our results broaden the understanding of
      the molecular adaptation process of human cancer cells to the microenvironment
      and might help to elaborate novel therapeutic concepts for the treatment of this
      pediatric liver tumor.

PMID- 29662634
TI  - Caloric restriction delays yeast chronological aging by remodeling carbohydrate
      and lipid metabolism, altering peroxisomal and mitochondrial functionalities, and
      postponing the onsets of apoptotic and liponecrotic modes of regulated cell
      death.
AB  - A dietary regimen of caloric restriction delays aging in evolutionarily distant
      eukaryotes, including the budding yeast Saccharomyces cerevisiae. Here, we
      assessed how caloric restriction influences morphological, biochemical and cell
      biological properties of chronologically aging yeast advancing through different
      stages of the aging process. Our findings revealed that this low-calorie diet
      slows yeast chronological aging by mechanisms that coordinate the spatiotemporal
      dynamics of various cellular processes before entry into a non-proliferative
      state and after such entry. Caloric restriction causes a stepwise establishment
      of an aging-delaying cellular pattern by tuning a network that assimilates the
      following: 1) pathways of carbohydrate and lipid metabolism; 2) communications
      between the endoplasmic reticulum, lipid droplets, peroxisomes, mitochondria and
      the cytosol; and 3) a balance between the processes of mitochondrial fusion and
      fission. Through different phases of the aging process, the caloric restriction
      dependent remodeling of this intricate network 1) postpones the age-related
      onsets of apoptotic and liponecrotic modes of regulated cell death; and 2)
      actively increases the chance of cell survival by supporting the maintenance of
      cellular proteostasis. Because caloric restriction decreases the risk of cell
      death and actively increases the chance of cell survival throughout chronological
      lifespan, this dietary intervention extends longevity of chronologically aging
      yeast.

PMID- 29662635
TI  - Establishment and characterization of two cabazitaxel-resistant prostate cancer
      cell lines.
AB  - Once castration-resistant prostate cancer (CRPC) become resistant for cabazitaxel
      treatment, the patients are obliged to best supportive care. Therefore, the
      elucidation of the mechanism of the cabazitaxel-resistance and the conquest are
      important themes to improve the prognosis of the patients. Then we tried to
      establish cabazitaxel-resistant CRPC cell lines and characterized them. We
      established two cabazitaxel-resistant cell lines, PC-3-TxR/CxR and DU145-TxR/CxR
      from PC-3-TxR and DU145-TxR cell lines previously we established. PC-3-TxR/CxR
      and DU145-TxR/CxR cells became resistant for cabazitaxel by 11.8-fold and 4.4
      fold, respectively. The TxR/CxR cells showed cabazitaxel-resistant using SCID
      mice in vivo. Although expression of multi-drug resistance gene 1 (MDR1) was up
      regulated in DU145-TxR compared with DU145 cells, it was not up-regulated in
      DU145-TxR/CxR cells any more. In contrast, expression of MDR1 gene was up
      regulated in PC-3-TxR compared with PC-3 cells and it was further up-regulated in
      PC-3-TxR/CxR compared with PC-3-TxR cells. Comparison of cDNA microarray between
      PC-3-TxR and PC-3-TxR/CxR cells or between DU145-TxR and DU145-TxR/CxR cells
      revealed that many genes were up-regulated or down-regulated. Finally, knockdown
      of MDR1 recovered the sensitivity to cabazitaxel not only in PC-3-TxR/CxR cells
      but also DU145-TxR/CxR cells. Together, regulation of MDR1 gene is important for
      conquest of the cabazitaxel-resistance.

PMID- 29662636
TI  - Analysis of hematological parameters as prognostic markers for toxicity and
      survival of 223Radium treatment.
AB  - 223Radium (223Ra) has emerged as treatment prolonging survival in patients with
      metastatic castration-resistant prostate cancer (CRPC). As 223Ra can cause
      hematotoxicity (HT), pre-existing hematopoiesis might influence the efficacy of
      223Ra and the rate of hematotoxicity, but as to our knowledge such data has not
      been published yet, we retrospectively conducted an analysis on patients
      receiving 223Ra. 54 patients treated with 223Ra had a median survival of 67
      weeks, which was significantly reduced in patients with pre-existing Hb toxicity
      (Tox) grade 2 (48 weeks P = 0.008) as compared to grade 1 (67 weeks) and normal
      levels of Hb (not reached); survival in patients with Plt Tox grade 1 was
      significantly reduced (44 weeks) as compared to normal Plt counts (71 weeks, P =
      0.033). Patients with impaired hematopoiesis regarding Hb and Plts developed
      significantly more grade 3 and 4 HT (Hb < 10 g/dl: 42.9% [3/7] vs 10.6% [5/47], P
      < 0.001; Plt < 150 G/L: 28.6% [2/7] vs 6.4% [3/47], P = 0.002) and received
      significantly fewer treatment cycles (Hb <10 g/dl: 5.1 vs 5.8, P = 0.04; Plt <
      150 G/L: 3.4 vs 5.6, P < 0.001). These results imply that pre-existing impaired
      hematopoiesis, in particular thrombocytopenia and anemia, before 223Ra therapy,
      is an important risk factor for worse outcome of treatment with 223Ra.

PMID- 29662637
TI  - The Wilms' tumor gene-1 is a prognostic factor in myelodysplastic syndrome: a
      meta analysis.
AB  - Previous studies have suggested that Wilms' tumor gene-1 (WT1) may be related to
      a decrease in both relapse-free survival (RFS) and overall survival (OS) for
      patients with myelodysplastic syndrome (MDS). Therefore, we conducted a meta
      analysis on the utility of WT1 as a prognostic indicator of MDS. Published
      reports were searched in the following databases: Cochrane Library, PubMed,
      Embase, and Web of Science. The meta-analysis was conducted using the Cochrane
      Collaboration RevMan 5.2 software. Six publications with 450 total patients met
      the inclusion criteria and were subjected to further examination. The results
      showed a reduction in both overall survival (OS) and leukemia-free survival (LFS)
      with increasing WT1 expression levels: 1-year OS (odds ratio, OR = 0.16; 95% CI =
      0.08-0.34, P < 0.001), 3-year OS (OR = 0.21; 95% CI = 0.09-0.47, P < 0.001), 5
      year OS (OR = 0.24; 95% CI = 0.06-0.92, P = 0.04), 1-year LFS (OR = 0.06; 95% CI
      = 0.02-0.18; P < 0.001), 3-year LFS (OR = 0.20; 95% CI = 0.09-0.46; P < 0.001),
      and 5-year LFS (OR = 0.12; 95% CI = 0.04-0.38; P < 0.001). In terms of patients
      receiving hematopoietic stem cell transplantation, the cumulative incidence of
      relapse (CIR) was higher in the WT1 over-expression group than in the low
      expression group: 1-year CIR (OR = 13.69; 95% CI = 2.99-62.62; P < 0.001), 3-year
      CIR (OR = 6.52; 95% CI = 2.31-18.40, P < 0.001). In conclusion, WT1 over
      expression is a prognostic factor for MDS.

PMID- 29662638
TI  - An open label, single-armed, exploratory study of apatinib (a novel VEGFR-2
      tyrosine kinase inhibitor) in patients with relapsed or refractory non-Hodgkin
      lymphoma.
AB  - Background: Apatinib, a novel small molecule vascular endothelial growth factor
      receptor-2 (VEGFR-2) tyrosine kinase inhibitor, have shown remarkable efficacy in
      many solid cancers. But evidence of antitumor activity in patients with lymphoma
      is still limited. We conducted an open-label, single-armed, exploratory study in
      relapse or refractory non-Hodgkin lymphoma patients for the efficacy and safety
      of apatinib. Experimental design: Patients with relapse or refractory non-Hodgkin
      patients meet the criteria were eligible for enrollment. Treatment comprised of
      oral apatinib 500 mg once daily with 21 days as a treatment cycle. The primary
      end point was response rate. Secondary end points included progression-free
      survival (PFS) and overall survival (OS). Results: Between February 2016 and
      December 2016, 21 patients were enrolled. The ORR (CR plus PR) was 47.6% (10 of
      21 patients) included 9.5% CRs and 38.1% PRs. 23.8% patients achieved stable
      disease made the DCR 71.4% (15/21). The median OS was 7.3 months (95% CI, 7.1 to
      7.9) and the median PFS was 7.1 months (95% CI, 4.2 to 7.3). Most patients
      suffered from grade 1 to grade 2 treatment-related adverse events and the most
      common nonhematologic adverse events were proteinuria (47.6%), hypertension
      (42.9%) and hand-foot syndrome (33.3%), respectively. Conclusions: In our study,
      the results we presented showed apatinib might have a rapid, safe and high
      efficacy on relapsed or refractory non-Hodgkin lymphoma patients. Based on the
      data more clinic trials are expected to be taken to identification the efficacy
      of apatinib on lymphoma further.

PMID- 29662639
TI  - Polymorphisms in BER genes and risk of breast cancer: evidences from 69 studies
      with 33760 cases and 33252 controls.
AB  - Recently, numerous studies have reported an association between single nucleotide
      polymorphisms in base-excision repair genes and the risk of developing breast
      cancer, however there is no consensus. The aim of this meta-analysis was to
      review and quantitatively assess the relationship between single nucleotide
      polymorphisms in base-excision repair genes and breast cancer risk. The results
      suggested that a mutation of T to G in rs1760944 may lead to a higher risk of
      developing breast cancer in the Mongoloid population, and G to A of rs25487
      significantly reduced the risk of breast cancer in Mongoloid and Caucasoid
      populations. In contrast to the CC and CG genotypes, the GG genotype of rs1052133
      located on theOGG1 gene appeared to be a protective factor against developing
      breast cancer in both Mongoloid and Caucasoid populations. There was no evidence
      to suggest that rs25489, rs1799782, rs1130409, rs1805414 and rs1136410 were
      associated with breast cancer risk. In conclusion, this study provides evidence
      to support the theory that DNA repair genes are associated with breast cancer
      risk, providing information to further understand breast cancer etiology. and The
      potential biological pathways linking DNA repair, ethnic background, environment
      and breast cancer require further investigation.

PMID- 29662640
TI  - Potential therapeutic targets of TP53 gene in the context of its classically
      canonical functions and its latest non-canonical functions in human cancer.
AB  - In normal tissue, p53 protein has a wide range of functions involving cell
      homeostasis; its mutation, however, permits a carcinogenic acquisition of
      function. TP53 gene mutation is a major genomic aberration in various human
      cancers and is a critical event in the multi-step carcinogenesis process. TP53
      mutation is clinically relevant for the molecular classification of
      carcinogenesis, as most recently described rigorously by the Cancer Genome Atlas
      Research Network. TP53 gene mutation has been considered to work as a tumor
      suppressor gene through the loss of its transcriptional activity, which is
      designated as a canonical function. However, in cancer patients with mutant TP53,
      mutated p53 protein is frequently overexpressed, suggesting the activation of an
      oncogenic process through a gain of function (GOF). As part of this GOF,
      molecular mechanisms explaining the non-canonical function of TP53 gene
      abnormality have been reported, in which mutant p53 unconventionally binds with
      various critical molecules suppressing oncogenic properties, such as p63 and p73.
      Moreover, mutant TP53 gene-targeted therapy has been rigorously developed, and
      promising clinical trials have been started. In this study, we summarize the
      novel aspects of mutant p53 and describe its prominent therapeutic potentials in
      human cancer.

PMID- 29662641
TI  - Signaling lymphocytic activation molecules Slam and cancers: friends or foes?
AB  - Signaling Lymphocytic Activation Molecules (SLAM) family receptors are initially
      described in immune cells. These receptors recruit both activating and inhibitory
      SH2 domain containing proteins through their Immunoreceptor Tyrosine based Switch
      Motifs (ITSMs). Accumulating evidence suggest that the members of this family are
      intimately involved in different physiological and pathophysiological events such
      as regulation of immune responses and entry pathways of certain viruses.
      Recently, other functions of SLAM, principally in the pathophysiology of
      neoplastic transformations have also been deciphered. These new findings may
      prompt SLAM to be considered as new tumor markers, diagnostic tools or potential
      therapeutic targets for controlling the tumor progression. In this review, we
      summarize the major observations describing the implications and features of SLAM
      in oncology and discuss the therapeutic potential attributed to these molecules.

PMID- 29662643
TI  - Correction: A comparison of the clinicopathological features and prognoses of the
      classical and the tall cell variant of papillary thyroid cancer: a meta-analysis.
AB  - [This corrects the article DOI: 10.18632/oncotarget.14055.].

PMID- 29662642
TI  - Successful retreatment with grazoprevir and elbasvir for patients infected with
      hepatitis C virus genotype 1b, who discontinued prior treatment with NS5A
      inhibitor-including regimens due to adverse events.
AB  - Background: Sustained virologic response (SVR) by interferon and interferon-free
      treatment can results in the reduction of advanced liver fibrosis and the
      occurrence of hepatocellular carcinoma in patients infected with hepatitis C
      virus (HCV). Recent interferon-free treatment for HCV shortens the duration of
      treatment and leads to higher SVR rates, without any serious adverse events.
      However, it is important to retreat patients who have had treatment-failure with
      HCV non-structural protein 5A (NS5A) inhibitor-including regimens. Combination of
      sofosbuvir and ledipasvir only leads to approximately 100% SVR rates in HCV
      genotype (GT1b), NS5A inhibitor-naive patients in Japan. This combination is not
      an indication for severe renal disease or heart disease, and these patients
      should be treated or retreated with a different regimen. Case summary:
      Retreatment with HCV non-structural protein 3/4A inhibitor, grazoprevir, and HCV
      NS5A inhibitor, elbasvir, successfully eradicated HCV RNA in three patients with
      HCV genotype 1b infection who discontinued prior interferon-free treatments
      including HCV NS5A inhibitors due to adverse events within 2 weeks. Conclusion:
      Retreatment with the 12-week combination regimen of grazoprevir and elbasvir is
      effective for HCV GT1b patients who discontinue the HCV NS5A inhibitor-including
      regimens within 2 weeks. The treatment response may be related to the short
      duration of initial treatment, which did not produce treatment-emergent RASs.

PMID- 29662644
TI  - Autoantibodies against islet cell antigens in children with type 1 diabetes
      mellitus.
AB  - We investigated the prevalence of glutamic acid decarboxylase 65 autoantibody
      (GADA), insulinoma-associated protein 2 autoantibody (IA2A), and insulin
      autoantibody (IAA) in 750 children with type 1 diabetes (T1D) living in Taiwan.
      GADA, IA2A, and IAA were measured by radioimmunoassay. The data were assessed by
      chi2 test, binary logistic regression, and Spearman rank correlation. Of the 750
      T1D patients, 66.3% had GADA, 65.3% IA2A, 35.7% IAA, and 17.2% no autoantibodies.
      The prevalence of GADA and IA2A significantly decreased along T1D duration. The
      positivity of either GADA or IA2A was 89.4% within the first year of disease and
      decreased to 36.7% after 9 years (P = 1.22 * 10-20). Female patients had
      significantly higher prevalence of GADA compared with male patients (72.3% vs.
      59.7%, P = 0.00027). The patients diagnosed before 12 years of age had a positive
      rate of 92.2% for either GADA or IA2A. Patients diagnosed at age 12 or above had
      a significantly lower positive rate of 81.6% (P = 0.011). GADA and IA2A
      significantly correlated with each other (rs = 0.245, P = 1.09 * 10-11). We
      concluded that autoantibodies were detectable in 89.4% of T1D patients within one
      year after diagnosis. Their prevalence declined with disease duration. GADA was
      more prevalent in female patients. GADA and IA2A weakly correlated with each
      other.

PMID- 29662645
TI  - A novel herbal formula, SGE, induces endoplasmic reticulum stress-mediated cancer
      cell death and alleviates cachexia symptoms induced by colon-26 adenocarcinoma.
AB  - Cachexia in cancer patients, characterized by marked involuntary weight loss and
      impaired physical function, is associated with a poor prognosis in response to
      conventional treatment and with an increase in cancer-related mortality.
      Prevention of skeletal muscle loss under cancer-induced cachexia via inhibition
      of pro-cachectic factors, as well as a reduction in tumor mass, has been
      considered reasonable pharmacological and nutritional interventions to treat
      cancer patients. In this study, we constructed a novel herbal formula, SGE, which
      contains Ginseng Radix alba, Atractylodis Rhizoma alba, and Hoelen, examined its
      anti-cancer and anti-cachexia efficacies. In in vitro experiments, SGE induced
      death of CT-26 murine colon carcinoma cells via endoplasmic reticulum stress, and
      suppressed the production of inflammatory cytokines in Raw 264.7 murine
      macrophage-like cells. In addition, SGE treatment attenuated CT-26-induced C2C12
      skeletal muscle cell atrophy as well as CT-26-induced reduction in lipid
      accumulation in 3T3-L1 adipocyte. In CT-26 tumor-bearing mice, daily oral
      administration of 10 and 50 mg/kg SGE remarkably attenuated the cachexia-related
      symptoms, including body weight and muscle loss, compared with saline treatment,
      while food intake was not affected. These data collectively suggest that SGE is
      beneficial as an anti-cancer adjuvant to treat cancer patients with severe weight
      loss.

PMID- 29662646
TI  - VHL status regulates transforming growth factor-beta signaling pathways in renal
      cell carcinoma.
AB  - To evaluate the role of pVHL in the regulation of TGF-beta signaling pathways in
      clear cell renal cell carcinoma (ccRCC) as well as in non-ccRCC; the expression
      of pVHL, and the TGF-beta pathway components and their association with
      clinicopathological parameters and patient's survival were explored. Tissue
      samples from 143 ccRCC and 58 non-ccRCC patients were examined by immunoblot.
      ccRCC cell lines were utilized for mechanistic in-vitro studies. Expression
      levels of pVHL were significantly lower in ccRCC compared with non-ccRCC. Non
      ccRCC and ccRCC pVHL-High expressed similar levels of pVHL. Expression of the TGF
      beta type I receptor (ALK5) and intra-cellular domain were significantly higher
      in ccRCC compared with non-ccRCC. In non-ccRCC, expressions of ALK5-FL, ALK5-ICD,
      pSMAD2/3, and PAI-1 had no association with clinicopathological parameters and
      survival. In ccRCC pVHL-Low, ALK5-FL, ALK5-ICD, pSMAD2/3, and PAI-1 were
      significantly related with tumor stage, size, and survival. In ccRCC pVHL-High,
      the expression of PAI-1 was associated with stage and survival. In-vitro studies
      revealed that pVHL interacted with ALK5 to downregulate its expression through
      K48-linked poly-ubiquitination and proteasomal degradation, thus negatively
      controlling TGF-beta induced cancer cell invasiveness. The pVHL status controls
      the ALK5 and can thereby regulate the TGF-beta pathway, aggressiveness of tumors,
      and survival of the ccRCC and non-ccRCC patients.

PMID- 29662647
TI  - Characterization of increasing stages of invasiveness identifies stromal/cancer
      cell crosstalk in rat models of mesothelioma.
AB  - Sarcomatoid mesothelioma (SM) is a devastating cancer associated with one of the
      poorest outcome. Therefore, representative preclinical models reproducing
      different tumor microenvironments (TME) observed in patients would open up new
      prospects for the identification of markers and evaluation of innovative
      therapies. Histological analyses of four original models of rat SM revealed their
      increasing infiltrative and metastatic potential were associated with differences
      in Ki67 index, blood-vessel density, and T-lymphocyte and macrophage
      infiltration. In comparison with the noninvasive tumor M5-T2, proteomic analysis
      demonstrated the three invasive tumors F4-T2, F5-T1 and M5-T1 shared in common a
      very significant increase in the abundance of the multifunctional proteins
      galectin-3, prohibitin and annexin A5, and a decrease in proteins involved in
      cell adhesion, tumor suppression, or epithelial differentiation. The increased
      metastatic potential of the F5-T1 tumor, relative to F4-T2, was associated with
      an increased macrophage vs T-cell infiltrate, changes in the levels of expression
      of a panel of cytokine genes, an increased content of proteins involved in
      chromatin organization, ribosome structure, splicing, or presenting anti-adhesive
      properties, and a decreased content of proteins involved in protection against
      oxidative stress, normoxia and intracellular trafficking. The most invasive
      tumor, M5-T1, was characterized by a pattern of specific phenotypic and molecular
      features affecting the presentation of MHC class I-mediated antigens and immune
      cell infiltration, or involved in the reorganization of the cytoskeleton and
      composition of the extracellular matrix. These four preclinical models and data
      represent a new resource available to the cancer research community to catalyze
      further investigations on invasiveness.

PMID- 29662648
TI  - Visceral abdominal fat measured by computer tomography as a prognostic factor for
      gynecological malignancies?
AB  - Introduction: Obesity is associated with increased incidence of ovarian (OC),
      cervical (CC) and endometrium cancer (EC). However, the impact of body
      composition (BC) on overall survival (OS), especially of visceral adipose tissue
      (VAT) is not yet understood. Methods: In 189 women with gynecological
      malignancies (31 OC, 104 CC, 54 EC, mean age 62.9y; mean BMI 26.8 kg/m2; median
      follow-up 30.7months) with routine staging CT-scans at baseline (mean interval:
      4.3 months), densitometric quantification of total (TAT), visceral, and
      subcutaneous-fat-area (SAT), inter-muscular-fat-area (IMFA), and skeletal-muscle
      index (SMI) was performed to analyze the impact of BC on survival. Results: With
      a mean follow-up of 30.7 months 48 patients had died. We observed no significant
      differences regarding BMI, the adipose- and muscle-distribution between surviving
      and deceased women. Univariate analyses revealed no significant BC-parameter with
      impact on OS, which was confirmed by different multivariate models. A subgroup
      analysis of OC, CC and EC showed only a protective impact of SMI on survival in
      the subgroup of CC. Conclusions: Despite the increased incidence of gynecological
      malignancies in obese, we found no significant impact of BC including VAT on
      patient survival. Further studies with larger cohorts are needed to quantify BC
      and its metabolomic impact regarding treatment and prognosis.

PMID- 29662649
TI  - 18FDG-PET/CT and molecular markers to predict response to neoadjuvant
      chemotherapy and outcome in HER2-negative advanced luminal breast cancers
      patients.
AB  - Background: The efficacy of neoadjuvant chemotherapy regimens in advanced luminal
      breast cancer patients is difficult to predict. Intrinsic properties of breast
      tumors, including altered gene expression profile and dynamic evaluation of
      metabolic properties of tumor cells using positron emission tomography/computed
      tomography (PET/CT) of tumor cells, have been identified to guide patient's
      prognosis. The aim of this study is to determine if both analyses may improve the
      prediction of response to neoadjuvant chemotherapy in ER-positive / HER2-negative
      breast cancers (BCs) patients. Methods: We used metabolic PET parameters, at
      diagnosis and after two cycles of chemotherapy and proliferation gene expression
      profile on biopsy at diagnosis, in particular, the genomic grade index (GGI)
      analyzed by reverse transcription and quantitative polymerase chain reaction (RT
      qPCR). The pathological response was the surrogate endpoint. Results: The change
      of FDG uptake between baseline PET and interim PET after 2 cycles of neoadjuvant
      chemotherapy (DeltaSUVmax) was highly associated with pCR (p=0.008). We also
      observed an ability of P53 mutated status (p=0.042), in addition to histological
      grade (p=0. 0004), and PR expression (p=0.01) to predict pCR in ER-positive BCs,
      whereas no proliferation marker predicted pCR (P=0.39 for GGI). Finally, only
      DeltaSUVmax was significantly associated with event free survival (p=0.047).
      Conclusions: Our results confirm the predictive and prognostic value of tumor
      DeltaSUVmax in ER-positive /HER2-negative advanced BCs patients. These findings
      can be helpful to select high-risk patients within trials investigating novel
      treatment strategies.

PMID- 29662650
TI  - HDL and associated factors stratified by sex and menopausal status: results from
      a community-based survey in Taiwan.
AB  - Aim: To investigate factors, especially modifiable factors associated with high
      density lipoprotein (HDL) in Taiwanese based on sex and menopausal status.
      Materials and Methods: Participants comprised 2022 men and 2392 women (1267
      menopausal and 1125 non-menopausal) aged >=30 years who resided in Pingzhen
      district, Taoyuan from 2006-2011. Their data, obtained through questionnaires and
      measurements were retrieved from the Li-Shin Hospital. Results: Higher HDL was
      associated with total cholesterol, underweight, and alcohol drinking in both men
      and women. It was also associated with education, blood group B, and marital
      status in men as well as with age in women. Moreover, it was associated with
      total cholesterol, underweight, and age in both menopausal and non-menopausal
      women. Furthermore, it was associated with marital status in non-menopausal women
      and alcohol drinking in menopausal women. Lower HDL was associated with
      triglycerides, low-density lipoprotein (LDL), overweight, obesity, waist-hip
      ratio (WHR), uric acid, and smoking in both men and women and with coffee
      drinking in only women. It was also associated with uric acid, triglycerides,
      LDL, overweight, obesity, WHR, and body fat in both menopausal and non-menopausal
      women. Moreover, it was associated with coffee drinking in menopausal women.
      Conclusion: Modifiable factors associated with HDL differ according to sex and
      menopausal status. Sex and menopausal status should be considered when
      implementing lifestyle changes to raise HDL. For example, both men and women
      should maintain a normal weight as well as quit smoking.

PMID- 29662651
TI  - p27Kip1 regulates alpha-synuclein expression.
AB  - Alpha-synuclein (alpha-SYN) is the main component of anomalous protein aggregates
      (Lewy bodies) that play a crucial role in several neurodegenerative diseases
      (synucleinopathies) like Parkinson's disease and multiple system atrophy.
      However, the mechanisms involved in its transcriptional regulation are poorly
      understood. We investigated here the role of the cyclin-dependent kinase (Cdk)
      inhibitor and transcriptional regulator p27Kip1 (p27) in the regulation of alpha
      SYN expression. We observed that selective deletion of p27 by CRISPR/Cas9
      technology in neural cells resulted in increased levels of alpha-SYN. Knock-down
      of the member of the same family p21Cip1 (p21) also led to increased alpha-SYN
      levels, indicating that p27 and p21 collaborate in the repression of alpha-SYN
      transcription. We demonstrated that this repression is mediated by the
      transcription factor E2F4 and the member of the retinoblastoma protein family
      p130 and that it is dependent of Cdk activity. Chromatin immunoprecipitation
      analysis revealed specific binding sites for p27, p21 and E2F4 in the proximal
      alpha-SYN gene promoter. Finally, luciferase assays revealed a direct action of
      p27, p21 and E2F4 in alpha-SYN gene expression. Our findings reveal for the first
      time a negative regulatory mechanism of alpha-SYN expression, suggesting a
      putative role for cell cycle regulators in the etiology of synucleinopathies.

PMID- 29662653
TI  - Plasma thymidine kinase-1 activity predicts outcome in patients with hormone
      receptor positive and HER2 negative metastatic breast cancer treated with
      endocrine therapy.
AB  - The aim of this study was to investigate if thymidine kinase-1 (TK1), a well
      known proliferation marker, could represent a valid circulating biomarker to
      identify hormone receptor positive (HR+)/HER2 negative (HER2neg) metastatic
      breast cancer (MBC) patients most likely to benefit from endocrine therapy (ET).
      We used the DiviTumTM assay to analyze TK1 activity in cell lysates of three
      HR+/HER2neg BC cell lines and in plasma of 31 HR+/HER2neg MBC patients receiving
      ET. Blood samples were collected at treatment initiation, after one month and at
      disease progression. CTCs count and ESR1/PIK3CA mutations in circulating tumor
      DNA were performed and correlated with TK1 activity. TK1 activity was reduced in
      the two endocrine-sensitive cell lines after 2 days of treatment. In patients,
      high baseline TK1 activity correlated with CTCs positivity (p-value=0.014).
      Patients with low baseline levels of TK1 activity had a significantly better PFS
      compared to those with high baseline TK1 activity (p-value=0.012). Patients with
      an early drop of TK1 activity after one month of treatment had a significantly
      better PFS compared to those who experienced an increase (p-value=0.0026). Our
      study suggests that TK1 could be a potential prognostic, predictive and
      monitoring marker of early ET response in HR+/HER2neg MBC patients.

PMID- 29662652
TI  - Guided bone regeneration using a bone tissue engineering complex consisting of a
      poly-dl-lactide membrane and bone mesenchymal stem cells.
AB  - Developmental dysplasia of the hip (DDH) is one of the most common diseases
      encountered in pediatric orthopedic departments. Current treatment strategies
      seek to improve acetabular coverage, the principal defect of acetabular
      dysplasia, but are not very successful. We developed a guided bone regeneration
      (GBR) strategy to improve acetabular coverage via bone tissue engineering (BTE).
      Poly-dl-lactide (PDLLA) membranes were seeded with bone marrow mesenchymal stem
      cells (BMSCs) to form a BTE complex, which was then implanted into the superior
      margin of the acetabulum in a rabbit DDH model. Twelve weeks later, a small
      amount of high-density shadowing was evident on X-rays of the superior margin of
      the acetabulum, specimens of which exhibited new bone formation. Micro-computed
      tomography yielding three-dimensional images revealed that new bone had formed in
      the superior acetabulum, the basal part of which had fused with (and thus
      reconstructed) the autogenous bone, and new trabecular bone featuring transverse
      interlacing was evident in the interior of the hip. No clear evidence of bone
      formation was observed in rabbits that underwent sham operations or that were
      implanted with PDLLA only. Thus, it may be possible to improve acetabular
      coverage via BTE-based bone regeneration.

PMID- 29662654
TI  - Extracellular vesicle-encapsulated miR-30e suppresses cholangiocarcinoma cell
      invasion and migration via inhibiting epithelial-mesenchymal transition.
AB  - Early-staged cholangiocarcinoma (CCA) is difficult to diagnose due to its high
      potential for invasion and metastasis. Epithelial-mesenchymal transition (EMT) is
      induced by transforming growth factor-beta (TGF-beta) in a process thought to be
      important for invasion and metastasis in several cancers, including CCA. Although
      microRNAs (miRNAs) have been implicated in the pathogenesis of several
      malignancies, their roles to CCA are not clearly understood. Some miRNAs were
      reported to be included in extracellular vesicles (EVs) and transferred from
      their donor cells to other cells, modulating recipient cell behaviors. In this
      study, the involvement and functional roles of EV-contained miRNAs during EMT in
      human CCA were determined. Expression profiling identified a subset of miRNAs
      that were reduced by TGF-beta in CCA cells. Among these, miR-30e was highly
      downregulated by TGF-beta and predicted to target Snail, which is an EMT
      inducible transcription factor. MiR-30e overexpression suppressed cell invasion
      and migration via inhibiting EMT, whereas miR-30e inhibition promoted EMT, cell
      invasion and migration. Moreover, miR-30e was enriched in EVs derived from CCA
      cells after miR-30e overexpression, and miR-30e intercellular transfer through
      EVs suppressed EMT, cell invasion and migration in recipient CCA cells. Together,
      our results suggest that EV-mediated miR-30e transfer could inhibit EMT via
      directly targeting Snail, which subsequently suppresses CCA cell invasion and
      migration. These findings provide several new insights into regulatory mechanisms
      of tumor invasion and metastasis in human CCA.

PMID- 29662655
TI  - Association of IL4, IL6, and IL10 polymorphisms with pulmonary tuberculosis in a
      Tibetan Chinese population.
AB  - Background: Pulmonary tuberculosis (PTB) is an infectious disease with a high
      incidence worldwide. Genes encoding cytokines IL4, IL6, and IL10 are highly
      polymorphic and can influence the susceptibility to PTB. Results: We found
      correlations between one SNP in IL6 (rs2069837 p = 6.63E-11), seven SNPs in IL10
      (rs1554286 p = 6.87E-20, rs1518111 p = 6.11E-11, rs3021094 p = 6.75E-29,
      rs3790622 p = 2.40E-06, rs3024490 p = 6.73E-11, rs1800872 p = 6.18E-11, rs1800871
      p = 6.73E-11) and incidences of PTB. The SNPs rs2069837, rs1554286, rs1518111,
      rs3024490, rs1800872, and rs1800871 increased PTB risk by 1.95-fold, 2.34-fold,
      1.84-fold, 1.84-fold, 1.84-fold and 1.84-fold, respectively. The SNPs rs3021094
      and rs3790622 decreased PTB risk by 0.33-fold and 0.38-fold, respectively. We
      also found two linkage disequilibrium blocks in the studied IL SNPs. The IL4
      haplotype TCCCGGA (OR = 1.33, p = 0.014) increased PTB risk, the IL10 haplotypes
      ATGGATA (OR = 0.39, p = 4.84E-06) provided a protective effect and decreased PTB
      risk. Materials and Methods: For this study, we recruited 467 subjects with PTB
      and 503 healthy subjects from a Tibetan population living in Lhasa and nearby,
      China. Association analyses of sixteen single-nucleotide polymorphisms (SNPs) in
      IL4, IL6, and IL10 were performed. Conclusions: Our findings demonstrate an
      association between polymorphisms in IL6 and IL10 and risk of PTB.

PMID- 29662656
TI  - Stereotactic body radiation therapy for palliative management of pancreatic
      adenocarcinoma in elderly and medically inoperable patients.
AB  - Stereotactic body radiation therapy (SBRT) represents a promising treatment
      option for patients with localized pancreatic ductal adenocarcinoma (PDAC) who
      cannot tolerate surgical therapy. We retrospectively reviewed the records of
      patients with localized PDAC treated with SBRT at our institution between 2010
      and 2016 to identify patients deemed medically inoperable due to poor performance
      status, advanced age, and/or comorbid conditions. Overall survival (OS),
      progression-free survival (PFS), and local progression-free survival (LPFS) were
      estimated using Kaplan-Meier curves. Twenty-nine patients were included. Median
      age was 74 (IQR 68-79). Thirteen patients (45%) had an Eastern Cooperative
      Oncology Group performance status of 2. Six patients (19%) had chronic
      obstructive pulmonary disease, 9 (31%) had cardiovascular disease, and 17 (58%)
      had diabetes mellitus. SBRT was delivered over 5 fractions to a median dose of 28
      Gy (IQR, 25-33). Twenty-two patients (76%) received induction chemotherapy prior
      to SBRT, and 9 (31%) received maintenance chemotherapy after SBRT. Median OS was
      13 months from diagnosis. Median OS and PFS were 8 and 6 months from SBRT,
      respectively. Six and 12-month LPFS rates were 91% and 78%, respectively.
      Patients receiving induction chemotherapy had superior survival from diagnosis
      than those who did not (14 vs. 7 months, p = 0.01). Three patients (10%)
      experienced acute grade >=3 toxicity, and 1 patient (4%) experienced grade >=3
      late toxicity. Symptom relief was achieved at three-month follow-up in 8 of 11
      patients (73%) experiencing abdominal pain. These results suggest SBRT may be
      safe and effective for patients who cannot tolerate surgery.

PMID- 29662657
TI  - 5'-nucleotidase cN-II emerges as a new predictive biomarker of response to
      gemcitabine/platinum combination chemotherapy in non-small cell lung cancer.
AB  - A number of pharmacogenetic studies have been carried out in non-small-cell lung
      cancer (NSCLC) to identify and characterize genes involved in chemotherapy
      activity. However, the results obtained so far are controversial and no reliable
      biomarker is currently used to predict clinical benefit from platinum-based
      chemotherapy, which represents the cornerstone of treatment of advanced NSCLC.
      This study investigated the expression levels of ERCC1 and of six genes (RRM1,
      RRM2, hENT1, dCK, cN-II and CDA) involved in gemcitabine metabolism in
      locally/advanced NSCLC patients treated with gemcitabine/platinum combination.
      Gene expression was assessed by quantitative-PCR in laser-microdissected
      specimens and correlated with tumor response. Frequency distribution of responses
      above and below the median expression level of biomarkers was compared using a
      two-sided Fisher's test. 5'-nucleotidase (cN-II) was the only gene differently
      expressed (p = 0.016) in the responders (complete/partial-response) compared to
      non-responders (stable/progressive disease). In the multivariate analysis,
      overexpression of this catabolic enzyme of gemcitabine remained a significant
      negative predictive factor. Patients with low cN-II had a modest trend toward
      increased survival, while both survival and progression-free survival were
      significantly longer in a more homogenous validation cohort of 40 advanced NSCLC
      (8.0 vs. 5.1 months, p = 0.026). Moreover, in vitro studies showed that silencing
      or pharmacological inhibition of cN-II increased the cytotoxicity of gemcitabine.
      This is the first study demonstrating the role of cN-II as a predictor of
      response to gemcitabine/platinum combinations in NSCLC. Its validation in
      prospective studies may improve clinical outcome of selected patients.

PMID- 29662658
TI  - Cross resistance to diverse anticancer nicotinamide phosphoribosyltransferase
      inhibitors induced by FK866 treatment.
AB  - Cross-resistance to drugs remains an unsolved problem in cancer chemotherapy.
      This study elucidates a molecular mechanism of cross-resistance to diverse
      inhibitors of nicotinamide phosphoribosyltransferase (NAMPT) with anticancer
      activity. We generated a variant of the human colon cancer cell line HCT116,
      HCT116RFK866, which exhibited primary resistance to the potent NAMPT inhibitor
      FK866, and was approximately 1,000-fold less sensitive to the drug than the
      parental HCT116. HCT116RFK866 was found to be cross-resistant to diverse NAMPT
      inhibitors, including CHS-828, GNE-617, and STF-118804. Whole-exon sequencing
      revealed two point mutations (H191R and K342R) in NAMPT in HCT116RFK866, only one
      of which (K342R) was present in the parental HCT116. Importantly, the protein
      level, NAMPT enzyme activity, and intracellular NAD+ level were similar between
      HCT116RFK866 and HCT116. Hence, we investigated NAMPT-binding partners in both
      cell lines by focused proteomic analyses. The amount of NAMPT precipitated with
      anti-NAMPT monoclonal antibody was much higher in HCT116RFK866 than in the
      parental. Furthermore, in HCT116, but not in HCT116RFK866, NAMPT was revealed to
      interact with POTE ankyrin domain family member E and beta-actin. Thus, these
      results suggest that NAMPT usually interacts with the two partner proteins, and
      the H191R mutation may prevent the interactions, resulting in resistance to
      diverse NAMPT inhibitors.

PMID- 29662659
TI  - IDH1 mutation is associated with lower expression of VEGF but not microvessel
      formation in glioblastoma multiforme.
AB  - Introduction: Glioblastoma multiforme (GBM) represents the most malignant primary
      brain tumor characterized by pathological vascularization. Mutations in
      isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) were observed in GBM. We aimed
      to assess the intra-tumor hypoxia, angiogenesis and microvessel formation in GBM
      and to find their associations with IDH1 mutation status and patients prognosis.
      Methods: 52 patients with a diagnosis of GBM were included into the study. IDH1
      R132H mutation was assessed by RT-PCR from FFPE tumor samples obtained during
      surgery. The expression of markers of hypoxia (HIF2alpha), angiogenesis (VEGF),
      tumor microvascularity (CD31, CD34, vWF, CD105), and proliferation (Ki-67) were
      assessed immunohistochemically (IHC). IDH1 mutation and IHC markers were
      correlated with the patient survival. Results: 20 from 52 GBM tumor samples
      comprised IDH1 R132H mutation (38.5%). The majority of mutated tumors were
      classified as secondary glioblastomas (89.9%). Patients with IDH1 mutated tumors
      experienced better progression-free survival (P = 0.037) as well as overall
      survival (P = 0.035) compared with wild type tumors. The significantly lower
      expression of VEGF was observed in GBM with IDH1 mutation than in wild type
      tumors (P = 0.01). No such association was found for microvascular markers. The
      increased expression of newly-formed microvessels (ratio CD105/CD31) in tumor
      samples was associated with worse patient's progression-free survival (P =
      0.026). Summary: No increase in HIF/VEGF-mediated angiogenesis was observed in
      IDH1-mutated GBM compared with IDH1 wild type tumors. The histological assessment
      of the portion of newly-formed microvessels in tumor tissue can be used for the
      prediction of GBM patient's prognosis.

PMID- 29662660
TI  - Clinical outcomes of women with ovarian metastases of colorectal cancer treated
      with oophorectomy with respect to their somatic mutation profiles.
AB  - We clarified the clinical prevalence of ovarian metastases from colorectal
      cancers (CRCs) in 296 female patients with CRC and evaluated clinical outcomes
      with relation to their mutational profiles, such as BRAF/KRAS mutation and
      microsatellite instability (MSI) status. The female CRCs were categorised into
      three subsets: CRCs with ovarian metastases [6.4% (n = 19), 5-year overall
      survival (OS) = 24.7%], CRCs with extra-ovarian metastases only [32.4% (n = 96),
      5-year OS = 34.5%] and CRCs without any recurrence or metastasis [61.2% (n =
      181), 5-year OS = 91.3%]. All patients with ovarian metastases underwent
      oophorectomy; of these, 9 who received preoperative chemotherapy had measurable
      metastases to extra-ovarian sites and the ovaries. Although 5 of 9 (56%) achieved
      partial response or complete response at extra-ovarian sites, no patient archived
      objective response at ovarian sites. Regarding the mutation profiles, in CRCs
      with extra-ovarian metastases only, the median survival time (MST) after initial
      treatments to progression to stage IV or recurrence was 13 [95% confidence
      interval (CI): 7-16 months] in BRAF-mutant and 34 months (95% CI: 22-58 months)
      in BRAF wild-type (P = 0.0033). Although ovarian metastases demonstrated poor
      response to systemic chemotherapy in CRCs with ovarian metastases, the MST after
      initial treatments to progression to stage IV or recurrence was 22 (95% CI: 21-25
      months) in BRAF-mutant and 38 months (95% CI: 24-42 months) in BRAF wild-type (P
      = 0.0398). The outcomes of patients with ovarian metastases could be improved by
      oophorectomy regardless of their mutation profiles.

PMID- 29662661
TI  - Targeting oncogenic Ras by the Clostridium perfringens toxin TpeL.
AB  - Clostridium perfringens toxin TpeL belongs to the family of large clostridial
      glycosylating toxins. The toxin causes N-acetylglucosaminylation of Ras proteins
      at threonine35 thereby inactivating the small GTPases. Here, we show that all
      main types of oncogenic Ras proteins (H-Ras, K-Ras and N-Ras) are modified by the
      toxin in vitro and in vivo. Toxin-catalyzed modification of Ras was accompanied
      by inhibition of the MAP kinase pathway. Importantly, TpeL inhibited the
      paradoxical activation of the MAP kinase pathway induced by the BRAF inhibitor
      Vemurafenib in the human melanoma cell line SBCL2. The toxin also blocked Ras
      signaling in a zebrafish embryo model expressing oncogenic H-RasG12V, resulting
      in a reduction of melanocyte number. By using the binding and translocation
      component of anthrax toxin (protective antigen), the glucosyltransferase domain
      of TpeL was effectively introduced into target cells that were not sensitive to
      native TpeL toxin. To reach a higher specificity towards cancer cells, a chimeric
      TpeL toxin was engineered that possessed the knob region of adenovirus serotype
      35 fiber, which interacts with CD46 of target cells frequently overexpressed in
      cancer cells. The chimeric TpeL fusion toxin efficiently inhibited Ras and MAP
      kinases in human pancreatic cancer Capan-2 cells, which were insensitive to the
      wild-type toxin. The data reveal that TpeL and TpeL-related immunotoxins provide
      a new toolset as Ras-inactivating agents.

PMID- 29662662
TI  - Health effects of a forest environment on natural killer cells in humans: an
      observational pilot study.
AB  - Health effect assessments based on natural killer (NK) cells are an important
      emerging area of human health. We recruited 90 forest staff members in Xitou,
      Taiwan and 110 urban staff members in Taipei to investigate the health effects of
      forest environment exposure on NK cells (CD3-/CD56+) and activating NK cells (CD3
      /CD56+/CD69+) in humans. We also invited 11 middle-aged volunteers in a pilot
      study to participate in a five-day/four-night forest trip to Xitou forest to
      investigate the health effects of a forest trip on NK cells and activating NK
      cells. Results showed that NK cells were higher in the forest group (19.5 +/-
      9.1%) than in the urban group (16.4 +/- 8.4%). In particular, the percentage of
      NK cells was significantly higher in the forest group than in the urban group
      among the subgroups of male, a higher body mass index (>= 25 kg/m2), without
      hypertension, lower high-sensitivity C-reactive protein, hyperglycemia, without
      smoking habit, and with tea drinking habit. After the five-day trip in Xitou
      forest, the percentage of activating NK cells of the invited participants from
      Taipei increased significantly after the trip to Xitou forest (0.83 +/- 0.39% vs.
      1.72 +/- 0.1%). The percentage of activating NK cells was 1.13 +/- 0.43%, which
      was higher than the baseline value of 0.77 +/- 0.38% before the forest trip among
      the seven subjects who participated in the follow-up study four days after
      returning to Taipei. This study suggests that exposure to forest environments
      might enhance the immune response of NK cells and activating NK cells in humans.

PMID- 29662663
TI  - Impact of antibiotic treatment on immune-checkpoint blockade efficacy in advanced
      non-squamous non-small cell lung cancer.
AB  - Introduction: Despite durable responses from immune-checkpoint blockade (ICB) in
      a subset of patients with advanced non-small cell lung cancer (NSCLC), the
      majority of patients do not derive benefit from this treatment. In this analysis
      we evaluated the impact of concomitant administration of antibiotics during
      initiation of ICB on clinical outcome. Methods: Advanced non-squamous NSCLC
      patients receiving ICB as second- or later line between 2015 and 2017 at our
      tertiary cancer center in Salzburg (Austria) were included. Concomitant use of
      antibiotics was defined as administration of antibiotics within a time frame of
      one month before or one month after initiation of ICB (AB+-group). Results: Of
      the 30 patients included, 11 (36.7%) received antibiotics one month before or one
      month after start of ICB (AB+-group). Median PFS on ICB was in favor of the AB-
      group (AB-: 3.1 months [95%CI: 3.0-16.3]; AB+: 2.9 months, [95%CI: 1.9-NA];
      HR=0.46 [95%CI: 0.12-0.90], p=0.031). Furthermore, median OS was significantly
      longer in the AB--group (AB-: 15.1 months [95%CI: 11.1-NA]; AB+: 7.5 months
      [95%CI: 6.3-NA]; HR=0.31 [95%CI: 0.02-0.78], p=0.026). In a multivariate
      analysis, the antibiotic treatment status was identified as the only parameter
      statistically significantly associated with PFS (p=0.028) and OS (p=0.026).
      Conclusions: Stratification of patients according to the antibiotic treatment
      status is warranted in future trials investigating ICB.

PMID- 29662664
TI  - Regulation of the antiapoptotic protein cFLIP by the glucocorticoid Dexamethasone
      in ALL cells.
AB  - We recently reported that the Smac mimetic BV6 and glucocorticoids, e.g.
      Dexamethasone (Dexa), synergize to induce cell death in acute lymphoblastic
      leukemia (ALL) in vitro and in vivo. Here, we discover that this synergism
      involves Dexa-stimulated downregulation of cellular FLICE-like inhibitory protein
      (cFLIP) in ALL cells. Dexa rapidly decreases cFLIPL protein levels, which is
      further enhanced by addition of BV6. While attenuating the activation of non
      canonical nuclear factor-kappaB (NF-kappaB) signaling by BV6, Dexa suppresses
      cFLIPL protein but not mRNA levels pointing to a transcription-independent
      downregulation of cFLIPL by Dexa. Analysis of protein degradation pathways
      indicates that Dexa causes cFLIPL depletion independently of proteasomal,
      lysosomal or caspase pathways, as inhibitors of the proteasome, lysosomal enzymes
      or caspases all failed to protect from Dexa-mediated loss of cFLIPL protein.
      Also, Dexa alone or in combination with BV6 does not affect overall activity of
      the proteasome. Importantly, overexpression of cFLIPL to an extent that is no
      longer subject to Dexa-imposed downregulation rescues Dexa/BV6-mediated cell
      death. Vice versa, knockdown of cFLIP increases BV6-mediated cell death, thus
      mimicking the effect of Dexa. Altogether, these data demonstrate that Dexa
      mediated downregulation of cFLIPL protein promotes Dexa/BV6-mediated cell death,
      thereby providing novel insights into the synergistic antitumor activity of this
      combination treatment.

PMID- 29662665
TI  - Molecular mechanism of action and potential biomarkers of growth inhibition of
      synergistic combination of afatinib and dasatinib against gefitinib-resistant non
      small cell lung cancer cells.
AB  - Epidermal growth factor receptor - tyrosine kinase inhibitor (EGFR-TKI) is the
      first choice of treatment for advanced non-small cell lung cancer (NSCLC)
      patients harbouring activating EGFR mutations. However, single agent usually has
      limited efficacy due to heterogeneous resistant mechanisms of cancer cells. Thus
      drug combination therapy would offer more benefits by synergistic interactions
      and avoidance of resistance emergence. In this study, we selected 8 NSCLC cell
      lines with different genetic characteristics as research models to investigate
      the efficacy of 4 agents (gefitinib, cetuximab, afatinib and dasatinib) and their
      combinations. As a single agent, both afatinib and dasatinib showed more
      inhibition against cell proliferation than gefitinib and cetuximab. Afatinib
      combined with dasatinib demonstrated significantly high efficacy against 7
      gefitinib-resistant NSCLC cell lines. Moreover, it reversed the resistance to the
      4 studied single agents in PTEN mutated NSCLC cells. By studying the activity of
      EGFR, Src and their downstream signalling pathways including PI3K/PTEN/Akt,
      Ras/Raf/MEK/ERK, Src/FAK and JAK/Stat, we demonstrated the synergistic
      interaction between afatinib and dasatinib was not only due to their blockage of
      different signalling pathways but also the complemental inhibition of the related
      signalling molecules such as Stat3. We also found that the level of Src, Stat3,
      and MAPK may be useful biomarkers predicating synergism between afatinib and
      dasatinib for the treatment of gefitinib-resistant NSCLC cells.

PMID- 29662666
TI  - CD30 expression and survival in extranodal NK/T-cell lymphoma: a systematic
      review and meta-analysis.
AB  - Background: The paradoxical reports about the prognostic value of the CD30
      expression in extranodal NK/T-cell lymphoma (ENKTL) have restricted its further
      applications in clinical practice. To identify the common effects and the
      variation, we conducted this systematic review and meta-analysis. Methods:
      PubMed, MEDLINE, Embase, and Web of Science were searched between January 1975
      and 31 January 2017. The pooled hazard ratio was used to estimate the effect of
      the CD30 expression on overall survival. Bias was assessed by prespecified
      criteria referring to Reporting Recommendations for Tumor Marker Prognostic
      Studies and Newcastle-Ottawa Scale. Results: Ten retrospective cohort studies
      with 310 patients are included. CD30 is associated with better overall survival
      significantly (HR 0.71, 95% CI 0.51 to 0.99, I2 = 0%). A greater effect is
      observed among studies including participants predominant in regional involvement
      (HR 0.31, 95%CI 0.13 to 0.76, I2 = 0%) compared with those in systemic
      involvement. Conclusions: This study indicates that the CD30 expression is
      significantly associated with better prognosis in ENKTL, especially for patients
      with regional lymphoma involvement.

PMID- 29662669
TI  - Corrigendum.
AB  - [This corrects the article DOI: 10.1177/2041669515613661.].

PMID- 29662667
TI  - Genetically enhanced T lymphocytes and the intensive care unit.
AB  - Chimeric antigen receptor-modified T cells (CAR-T cells) and donor lymphocyte
      infusion (DLI) are important protocols in lymphocyte engineering. CAR-T cells
      have emerged as a new modality for cancer immunotherapy due to their potential
      efficacy against hematological malignancies. These genetically modified receptors
      contain an antigen-binding moiety, a hinge region, a transmembrane domain, and an
      intracellular costimulatory domain resulting in lymphocyte T cell activation
      subsequent to antigen binding. In present-day medicine, four generations of CAR-T
      cells are described depending on the intracellular signaling domain number of T
      cell receptors. DLI represents a form of adoptive therapy used after
      hematopoietic stem cell transplant for its anti-tumor and anti-infectious
      properties. This article covers the current status of CAR-T cells and DLI
      research in the intensive care unit (ICU) patient, including the efficacy,
      toxicity, side effects and treatment.

PMID- 29662668
TI  - Proteomic biomarkers in body fluids associated with pancreatic cancer.
AB  - Pancreatic cancer (PC) is a highly malignant disease that represents the fourth
      leading cancer-related death worldwide. There has been very little improvement in
      survival rates over recent years, and surgical resection remains the only
      reliable curative approach. Factors that contribute to this dismal prognosis for
      PC include its rapid progression and invasion, the absence of specific symptoms,
      and the little impact of available chemotherapy. Importantly, the management of
      this malignancy is also limited by the lack of highly specific and sensitive
      biomarkers for its diagnosis and follow-up, and their identification is therefore
      considered a promising strategy to improve outcomes in these patients. Numerous
      translational studies have explored the usefulness of body fluids as a non
      invasive source of PC-specific biomarkers, and innovations in proteomic methods
      and technologies have provided a myriad of protein biomarkers for different
      cancers. The adoption of a proteomic approach has improved understanding of the
      biology of PC and contributed to the potential identification of protein
      biomarkers for this disease. This review considers the most recent research
      efforts to develop novel proteomic biomarkers in body fluids for PC.

PMID- 29662670
TI  - Extended bioreactor conditioning of mononuclear cell-seeded heart valve
      scaffolds.
AB  - The tissue-engineered heart valve may be the ideal valve replacement option but
      still must overcome challenges in leaflet recellularization. This study sought to
      investigate the potential for leaflet matrix restoration and repopulation
      following mononuclear cell seeding and extended periods of bioreactor
      conditioning. Human aortic heart valves were seeded with mononuclear cells and
      conditioned in a pulsatile bioreactor for 3 days, 3 weeks, or 6 weeks. The
      results of this study determined that a mononuclear cell population can be
      readily localized within the leaflet tissue in as little as 3 days. Furthermore,
      as extended bioreactor condition continued to the 3- and 6-week time points, the
      mesenchymal stem cell subfraction proliferated and appeared to become the
      predominant cell phenotype. This was evident through positive expression of
      mesenchymal stem cell markers and no expression of mononuclear cell markers
      observed by immunohistochemistry in the 3- and 6-week groups. In addition, cells
      in the 3- and 6-week groups exhibited an up-regulation of mesenchymal stem cell
      associated genes (THY1, NT5E, and ITGB1) and a down-regulation of mononuclear
      cell-associated genes (CD14, ICAM1, and PECAM1) compared to the initial seeded
      cell population. However, repopulation of the leaflet interstitium was less
      extensive than anticipated. Valves in the 6-week time point also exhibited
      retracted leaflets. Thus, while the 3-week bioreactor-conditioning period used in
      this study may hold some promise, a bioreactor-conditioning period of 6 weeks is
      not a viable option for clinical translation due to the negative impact on valve
      performance.

PMID- 29662672
TI  - Results of a local combination therapy antibiogram for Pseudomonas aeruginosa
      isolates: is double worth the trouble?
AB  - Purpose: To determine the frequency at which fluoroquinolones and aminoglycosides
      demonstrate in vitro activity against non-urinary, non-skin/skin structure
      Pseudomonas aeruginosa isolates exhibiting decreased susceptibilities to one or
      more beta-lactam agents. Methods: beta-lactam-non-susceptible P. aeruginosa
      isolates recovered from blood, bone, lower respiratory tract, pleural fluid,
      cerebrospinal fluid, or peritoneal fluid cultures between October 2010 and
      October 2014 were reviewed from four community hospitals within a single health
      system. Only the first isolate per patient was included for analysis. The
      likelihood that each isolate was susceptible to a non-beta-lactam antimicrobial
      was then determined and summarized within a combination antibiogram. Results: In
      total, 179 P. aeruginosa isolates with decreased susceptibilities to one or more
      beta-lactam agents were assessed. Because no appreciable differences in
      antimicrobial susceptibility profile were observed between hospitals, the
      isolates were evaluated in aggregate. Susceptibility rates for beta-lactam
      monotherapy ranged from 34% to 75%. Aminoglycosides possessed increased
      antibacterial activity compared to fluoroquinolones. Tobramycin was the non-beta
      lactam most likely to expand antimicrobial coverage against beta-lactam-non
      susceptible P. aeruginosa with activity against 64%, 66%, and 65% of cefepime-,
      piperacillin-tazobactam-, and meropenem-non-susceptible isolates, respectively (p
      < 0.001 for all). Conclusions: The results of this study support the use of
      aminoglycosides over fluoroquinolones for achieving optimal, empiric
      antimicrobial combination therapy for P. aeruginosa when dual antimicrobial
      therapy is clinically necessary. Future efforts aimed at optimizing combination
      therapy for P. aeruginosa should focus on systemic interventions that limit the
      selection of fluoroquinolones in combination with beta-lactams to expand coverage
      based on local susceptibility rates.

PMID- 29662674
TI  - Corrigendum.
AB  - [This corrects the article DOI: 10.1177/2049936117690501.].

PMID- 29662675
TI  - Anterior versus posterior approach to treat cervical spondylotic myelopathy,
      clinical and radiological results with long period of follow-up.
AB  - Background: Cervical spondylotic myelopathy increases with age, but not all cases
      are symptomatic. It is usually diagnosed clinically and radiologically (X-ray and
      magnetic resonance imaging). Surgical treatment is indicated in severe
      symptomatic cases, while treatment controversy exists in the presence of less
      severe cases. Anterior and posterior approaches are generally used for
      decompression with no significant differences in the results of both. Methods: A
      total of 287 patients of cervical spondylotic myelopathy were treated at our
      hospital between January 2004 and December 2015. Only 140 patients were eligible
      for our study. They had at least 5 years of follow-up using full clinical scores
      and radiological evaluation. They were divided into two groups: group I with 73
      patients (aged 23-79 years) underwent posterior decompression, lateral mass
      instrumentation, and fusion, while group II with 67 patients (aged 33-70 years)
      underwent anterior decompression, instrumentation, and fusion. Neck Disability
      Index, local score, and X-ray were used in the evaluation of the patients.
      Results: Preoperative mean +/- standard deviation of Neck Disability Index of
      both the groups was 32.06 +/- 6.33 and 29.88 +/- 5.48, which improved in the last
      visit (>5 years) to 5.81 +/- 7.39 and 2.94 +/- 5.48 for groups I and II,
      respectively (p value <0.05). The local score of groups I and II was (P = 1, F =
      21, G = 31, E = 19) and (P = 1, F = 12, G = 36, E = 18), which on discharge day
      improved to (P = 1, F = 4, G = 12, E = 55) and (P = 0, F = 3, G = 6, E = 58) at
      last follow-up, respectively. Fusion rate was nearly equal for both the groups
      during all the follow-up intervals and it was 91.1% and 91.7% in the last follow
      up. Conclusion: There were no significant differences in the clinical and
      radiological results between the anterior and posterior approaches used in the
      surgical treatment of spondylotic cervical myelopathy. However, statistically
      significant results of Neck Disability Index of anterior approach were not
      clinically important and may be due to changes in the size and shape of the neck
      in group II.

PMID- 29662673
TI  - Epidemiology and management of healthcare-associated bloodstream infections in
      non-neutropenic immunosuppressed patients: a review of the literature.
AB  - Advancements in medicine have led to a considerable increase in the proportion of
      patients living with severe chronic diseases, malignancies, and HIV infections.
      Most of these conditions are associated with acquired immune-deficient states and
      treatment-related immunosuppression. Although infections as a result of
      neutropenia have long been recognized and strategies for management were
      developed, non-neutropenic immunosuppression has been overlooked. Recently,
      community-acquired infections in patients with frequent, significant exposure to
      healthcare settings and procedures have been classified as 'healthcare-associated
      infections' since they are more similar to hospital-acquired infections. Most of
      the non-neutropenic immunosuppressed patients have frequent contact with the
      healthcare system due to their chronic and severe diseases. In this review, we
      focus on the healthcare-associated bloodstream infections in the most common non
      neutropenic immunosuppressive states and provide an update of the recent evidence
      for the management of these infections.

PMID- 29662676
TI  - Toxoplasma gondii exposure and epilepsy: A matched case-control study in a public
      hospital in northern Mexico.
AB  - Objectives: This study aimed to determine the association between infection with
      Toxoplasma gondii and epilepsy in patients attended to in a public hospital in
      the northern Mexican city of Durango. Methods: We performed an age- and gender
      matched case-control study of 99 patients suffering from epilepsy and 99 without
      epilepsy. Sera of participants were analyzed for anti-T. gondii IgG and IgM
      antibodies using commercially available enzyme-linked immunoassays. Seropositive
      samples to T. gondii were further analyzed for detection of T. gondii DNA by
      polymerase chain reaction. Results: Anti-T. gondii IgG antibodies were found in
      10 (10.1%) of the 99 cases and in 6 (6.1%) of the 99 controls (odds ratio = 1.74;
      95% confidence interval: 0.60-4.99; p = 0.43). High (> 150 IU/mL) levels of anti
      T. gondii IgG antibodies were found in 6 of the 99 cases and in 4 of the 99
      controls (odds ratio = 1.53; 95% confidence interval: 0.41-5.60; p = 0.74). Anti
      T. gondii IgM antibodies were found in 2 of the 10 IgG seropositive cases, and in
      2 of the 6 IgG seropositive controls (odds ratio = 0.50; 95% confidence interval:
      0.05-4.97; p = 0.60). T. gondii DNA was not found in any of the 10 anti-T. gondii
      IgG positive patients. Bivariate analysis of IgG seropositivity to T. gondii and
      International Statistical Classification of Diseases and related Health Problems,
      10th Edition codes of epilepsy showed an association between seropositivity and
      G40.1 code (odds ratio = 22.0; 95% confidence interval: 2.59-186.5; p = 0.008).
      Logistic regression analysis showed an association between T. gondii infection
      and consumption of goat meat (odds ratio = 6.5; 95% confidence interval: 1.22
      34.64; p = 0.02), unwashed raw vegetables (odds ratio = 26.3; 95% confidence
      interval: 2.61-265.23; p = 0.006), and tobacco use (odds ratio = 6.2; 95%
      confidence interval: 1.06-36.66; p = 0.04). Conclusions: Results suggest that T.
      gondii infection does not increase the risk of epilepsy in our setting; however,
      infection might be linked to specific types of epilepsy. Factors associated with
      T. gondii infection found in this study may aid in the design of preventive
      measures against toxoplasmosis.

PMID- 29662677
TI  - Auto-antibodies against P/Q- and N-type voltage-dependent calcium channels
      mimicking frontotemporal dementia.
AB  - The behavioral variant of frontotemporal dementia is usually a sporadic and
      progressive neurodegenerative disorder. Here, we report the subacute onset of a
      frontotemporal dementia phenotype with a treatable etiology. The patient has a
      history of rheumatoid arthritis, episcleritis, and thyroid eye disease on
      immunosuppressive therapy. He experienced a rapid personality change, including
      inappropriate behavior, which suggested frontotemporal dementia. Results of
      imaging and neuropsychological testing also suggested frontotemporal dementia.
      Because of his autoimmune diseases and unusually short onset of symptoms, serum
      paraneoplastic panel and cerebrospinal fluid were analyzed and revealed elevated
      P/Q- and N-type calcium channel antibodies. Treatment with therapeutic plasma
      exchange resulted in a rapid improvement of his behavior and cognition. This case
      suggests that there may be some treatable causes of frontotemporal dementia
      symptomatology, that is, paraneoplastic antibodies. In the context of atypical
      features of frontotemporal dementia, practitioners should maintain a high index
      of suspicion.

PMID- 29662678
TI  - Interleukin-6 is a key factor for immunoglobulin-like transcript-4-mediated
      immune injury in sepsis.
AB  - Background: ILT4+ monocytes seem to be associated with poor prognosis of sepsis
      in humans, but the exact mechanisms are unknown. This study aimed to examine the
      biological behaviors and effects of immunoglobulin-like transcript-4 (ILT4)
      levels on monocytes during sepsis and on the prognosis of sepsis. Methods:
      ILT4+/+ (WT) and ILT4-knockout (ILT4-/-) male BALB/c mice were used for sepsis
      modeling using cecal ligation puncture (CLP). Flow cytometry was used to measure
      the levels of ILT4 and major histocompatibility complex class II (MHC-II) on
      peripheral blood monocytes 24 h after CLP. ELISA was used to measure the serum
      levels of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6,
      and IL-12 at 0, 6, 12, and 24 h after CLP. Survival and prognosis were monitored
      over the course of 168 h. Results: ILT4 was highly expressed in peripheral blood
      monocytes of septic mice 24 h after CLP (1292.00 +/- 143.70 vs. 193.50 +/- 52.54,
      p < 0.05). MHC-II levels on peripheral blood monocytes in ILT4-/- mice were
      significantly higher than those in WT mice (49.38 +/- 5.66% vs. 24.25 +/- 6.76%,
      p < 0.05). Serum IL-6 was significantly elevated 24 h after CLP (470.75 +/- 88.03
      vs. 54.25 +/- 20.04, p < 0.05). The serum IL-6 levels were significantly lower in
      ILT4-/- mice compared with those in WT mice after CLP (241.25 +/- 45.10 vs.
      470.75 +/- 88.03, p < 0.05), but TNF-alpha, IL-1beta, and IL-12 were not changed.
      The survival of ILT4-/- mice was significantly better after CLP compared with
      that of WT mice. Conclusions: High levels of ILT4 on monocytes were observed in
      peripheral blood during sepsis and found to be associated with high serum IL-6
      levels and low MHC-II levels on monocytes, possibly associated with higher
      mortality. ILT-4-IL-6-MHC-II could be a potential signaling pathway involved in
      sepsis.

PMID- 29662680
TI  - Erratum.
AB  - [This corrects the article DOI: 10.1177/2055102917718376.][This corrects the
      article DOI: 10.1177/2055102917709375.][This corrects the article DOI:
      10.1177/2055102917716205.].

PMID- 29662679
TI  - Validation of Living Donor Nephrectomy Codes.
AB  - Background: Use of administrative data for outcomes assessment in living kidney
      donors is increasing given the rarity of complications and challenges with loss
      to follow-up. Objective: To assess the validity of living donor nephrectomy in
      health care administrative databases compared with the reference standard of
      manual chart review. Design: Retrospective cohort study. Setting: 5 major
      transplant centers in Ontario, Canada. Patients: Living kidney donors between
      2003 and 2010. Measurements: Sensitivity and positive predictive value (PPV).
      Methods: Using administrative databases, we conducted a retrospective study to
      determine the validity of diagnostic and procedural codes for living donor
      nephrectomies. The reference standard was living donor nephrectomies identified
      through the province's tissue and organ procurement agency, with verification by
      manual chart review. Operating characteristics (sensitivity and PPV) of various
      algorithms using diagnostic, procedural, and physician billing codes were
      calculated. Results: During the study period, there were a total of 1199 living
      donor nephrectomies. Overall, the best algorithm for identifying living kidney
      donors was the presence of 1 diagnostic code for kidney donor (ICD-10 Z52.4) and
      1 procedural code for kidney procurement/excision (1PC58, 1PC89, 1PC91). Compared
      with the reference standard, this algorithm had a sensitivity of 97% and a PPV of
      90%. The diagnostic and procedural codes performed better than the physician
      billing codes (sensitivity 60%, PPV 78%). Limitations: The donor chart review and
      validation study was performed in Ontario and may not be generalizable to other
      regions. Conclusions: An algorithm consisting of 1 diagnostic and 1 procedural
      code can be reliably used to conduct health services research that requires the
      accurate determination of living kidney donors at the population level.

PMID- 29662681
TI  - Willingness to trade-off: An intermediate factor in patient decision-making
      regarding escalating care.
AB  - This study aimed to evaluate treatment necessity, treatment concern, and
      willingness to engage in decisional trade-offs in the context of treatment
      escalation decision-making. Participants (n = 147) recruited online were
      randomized to read a vignette about escalating care in psoriasis in a 2 (high
      treatment concern vs moderate treatment concern) * 2 (high perceived treatment
      necessity vs moderate perceived treatment necessity) design. High treatment
      concern was associated with choosing to defer treatment escalation and being
      unwilling to engage in decisional trade-offs if disease risk changed. Results
      highlight the importance of treatment concern and willingness trade-off in
      treatment escalation decision-making.

PMID- 29662682
TI  - Delayed intestinal perforation secondary to blunt force abdominal trauma in a
      cat.
AB  - Case summary: A 7-month-old intact male domestic shorthair cat was presented 4 h
      after being hit by a car. It had bilateral inguinal hernias and a mesenteric rent
      that were repaired surgically and a hematoma in the left retroperitoneal space.
      No other intra-abdominal abnormalities were identified on abdominal surgical
      exploration. Approximately 72 h after presentation, the cat started vomiting and
      developed severe abdominal discomfort. A sudden decrease in mentation and
      elevation of respiratory rate and effort ensued. Abdominal radiographs showed
      loss of detail in the abdominal cavity, and abdominocentesis confirmed septic
      peritonitis. The cat was euthanized, and post-mortem evaluation of the bowel
      revealed two 1 cm perforations of the jejunum. Relevance and novel information:
      To our knowledge, delayed intestinal perforation secondary to blunt force
      abdominal trauma has not previously been reported in cats. It has been reported
      in dogs, but the pathophysiology resulting in perforation is poorly understood.
      Delayed intestinal injury secondary to blunt force abdominal trauma has been
      reported in people, especially in children, as a result of motor vehicle
      accidents.

PMID- 29662683
TI  - Coexistence of systemic lupus erythematosus and multiple sclerosis. A case report
      and literature review.
AB  - Multiple sclerosis (MS) and systemic lupus erythematous (SLE) are autoimmune
      diseases, the coexistence of which is uncommon in patients. Owing to the rarity
      of this condition, the distinction between MS and SLE is a diagnostic challenge
      for neurologists. We present a case report in which MS and SLE were present in
      the same patient. There are few case reports in the world on the association
      between MS and SLE. The following case report is the first of its kind in which
      both MS and SLE are present in a patient from a country with low prevalence of MS
      such as Ecuador.

PMID- 29662684
TI  - A comparison of combined oral contraceptives containing chlormadinone acetate
      versus drospirenone for the treatment of acne and dysmenorrhea: a randomized
      trial.
AB  - Background: Oral contraceptives (OCs), aside from contraceptive efficacy, have
      been widely known for their non-contraceptive benefits. Different progestogens
      component of the OCs have been shown to improve the skin, hair, menstrual cycle
      related disorders and dysmenorrhoeic pain. Thus, we compared the efficacy of OCs
      containing ethinyl estradiol (EE) and chlormadinone acetate (CMA) versus OCs
      containing EE and drospirenone (DRSP) for the treatment of acne and dysmenorrhea.
      Methods: This study was an investigator-blinded, randomized, parallel group study
      conducted at the Family Planning Clinic, Department of Obstetrics and
      Gynaecology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
      Women aged between 18 and 45 years were randomly assigned into two treatment
      groups, either EE/CMA at the dosage of 30 mcg/2 mg once daily (OD) or EE/DRSP at
      the dosage of 30 mcg/3 mg OD. The subjects were evaluated for the OC's efficacy
      for the treatment of acne and dysmenorrhea at baseline visit and after 1, 3, and
      6 months of treatment. Results: A total of 180 women were randomized into the
      study. Each group had 90 women. Baseline characteristics between both groups were
      comparable. At Month 6, there was a significantly greater reduction of total acne
      lesion in the EE/CMA group than EE/DRSP (72.2% vs 64.5%; p = 0.009). As per the
      investigator's global assessment of acne treatment, a higher proportion of the
      subjects from the EE/CMA group was rated "excellent" than those from the EE/DRSP
      (75.3% vs 49.4%). More subjects from the EE/CMA group had graded their
      improvement in acne as "excellent" compared to the EE/DRSP group (66.3% vs
      48.3%). A higher proportion of the subjects in the EE/CMA group reported a
      decrease in dysmenorrhoeic pain as "much decrease" and "decrease". The absence of
      dysmenorrhea pain was more frequently found in the EE/CMA group and significantly
      seen as early as Month 1 also in the EE/CMA group compared to EE/DRSP (47.2% vs
      27.3%, respectively). The treatments were generally well-tolerated in both
      groups. There were no significant differences between both groups for adverse
      events. Conclusions: EE/CMA is more effective for the treatment of acne and
      dysmenorrhea in women with mild to moderate acne vulgaris and dysmenorrhea than
      EE/DRSP. Trial registration: Thai Clinical Trial Registry ID: TCTR20170518001
      (date of registration: May 17, 2017; retrospectively registered).

PMID- 29662685
TI  - Adaptation, translation and reliability of the Australian 'Juniors Enjoying
      Cricket Safely' injury risk perception questionnaire for Sri Lanka.
AB  - Objectives: Cricket is a very popular sport in Sri Lanka. In this setting there
      has been limited research; specifically, there is little knowledge of cricket
      injuries. To support future research possibilities, the aim of this study was to
      cross-culturally adapt, translate and test the reliability of an Australian
      developed questionnaire for the Sri Lankan context. Methods: The Australian
      'Juniors Enjoying Cricket Safely' (JECS-Aus) injury risk perception questionnaire
      was cross-culturally adapted to suit the Sri Lankan context and subsequently
      translated into the two main languages (Sinhala and Tamil) based on standard
      forward-back translation. The translated questionnaires were examined for content
      validity by two language schoolteachers. The questionnaires were completed twice,
      2 weeks apart, by two groups of school cricketers (males) aged 11-15 years
      (Sinhala (n=24), Tamil (n=30)) to assess reliability. Test-retest scores were
      evaluated for agreement. Where responses were <100% agreement, Cohen's kappa
      (kappa) statistics were calculated. Questions with moderate-to-poor test-retest
      reliability (kappa<0.6) were reconsidered for modification. Results: Both the
      Sinhala and Tamil questionnaires had 100% agreement for questions on demographic
      data, and 88%-100% agreement for questions on participation in cricket and injury
      history. Of the injury risk perception questions, 72% (Sinhala) and 90% (Tamil)
      questions showed a substantial (kappa=0.61-0.8) and almost perfect (kappa=0.81
      1.0) test-retest agreement. Conclusion: The adapted and translated JECS-SL
      questionnaire demonstrated strong reliability. This is the first study to adapt
      the JECS-Aus questionnaire for use in a different population, providing an
      outcome measure for assessing injury risk perceptions in Sri Lankan junior
      cricketers.

PMID- 29662686
TI  - Patterns of physical activity in sedentary older individuals with type 2
      diabetes.
AB  - Background: The Community Healthy Activities Model Program for Seniors (CHAMPS)
      survey, summarized into weekly caloric expenditures, is a common physical
      activity (PA) assessment tool among older adults. Specific types of PA reported
      in the CHAMPS have not been systematically analyzed. We applied latent class
      analysis to identify the patterns of PA among sedentary older adults with
      diabetes reported in the CHAMPS survey. Methods: Latent class models of PA were
      identified using the CHAMPS survey data reported by 115 individuals aged >=60
      years with type 2 diabetes whom volunteered for a clinical study of PA.
      Multinomial logistic regression was used to assess independent predictors of a
      specific latent class, including age, sex, and performance in physical function
      tests. Results: Ninety-three percent of the participants were classified into 3
      latent classes. Participants in latent class 1 (60.9%) primarily reported
      domestic-focused activities. Participants in latent class 2 and 3 (19.5% and
      19.6%, respectively) reported domestic-focused activities, in addition to leisure
      time physical activities and structured exercise activities. Latent class 1, with
      more women than men (73% vs.27%), had the lowest caloric expenditure, whereas
      class 3, with fewer women than men (28% vs. 72%), had the highest caloric
      expenditure (all p < 0.001). Latent class 2 had the fastest Timed-Up- and Go
      (7.65 +/- 1.28 s; p = 0.03). Conclusions: Individual PA response in CHAMPS can be
      categorized using latent class models into meaningful patterns which can inform
      PA interventions. Customized PA programs should consider the heterogeneity of the
      activities among sedentary older adults. Trial Registration: ClinicalTrials.gov
      Identifier NCT00344240; retrospectively registered 23 June 2006.

PMID- 29662687
TI  - Efficacy of percutaneous transhepatic portal vein embolization using gelatin
      sponge particles and metal coils.
AB  - Background: Percutaneous transhepatic portal vein embolization (PTPE) can
      increase the future liver remnant (FLR) volume before extended liver resection;
      however, there is no current consensus regarding the best embolic material for
      PTPE. Purpose: To evaluate the efficacy of PTPE using gelatin sponge particles
      and coils. Material and Methods: The medical records of 136 patients who
      underwent PTPE using gelatin sponge particles and metal coils were
      retrospectively reviewed. We evaluated the procedural details, liver volume on
      CT, and clinical status before and after PTPE. Results: The mean FLR volume
      increased significantly from 390 +/- 147 cm3 to 508 +/- 141 cm3 (P < 0.001). A
      mean of 22.1 +/- 9.4 days after PTPE, the mean increase in the ratio of FLR
      volume to total liver volume was 9.4 +/- 6.5%. Complications related to PTPE
      occurred in five patients, including arterial damage (n = 4) and biloma (n = 1).
      The white blood cell count and C-reactive protein level increased significantly
      and then returned to baseline within seven days. Aspartate aminotransferase and
      alanine aminotransferase showed no significant changes. Fever (defined by the
      Common Terminology Criteria for Adverse Events v4.0) was reported in 74 patients
      (54%), but it was generally mild (Grade 1/2; n = 72). None of the patients
      experienced severe complications that required cancellation of surgery.
      Conclusion: PTPE with gelatin sponge particles and coils may impose low physical
      stress on patients and is a safe method of inducing a significant increase of
      FLR.

PMID- 29662688
TI  - Distribution and determinants of pneumonia diagnosis using Integrated Management
      of Childhood Illness guidelines: a nationally representative study in Malawi.
AB  - Background: Pneumonia remains the leading cause of child mortality in sub-Saharan
      Africa. The Integrated Management of Childhood Illness (IMCI) strategy was
      developed to standardise care in low-income and middle-income countries for major
      childhood illnesses and can effectively improve healthcare worker performance.
      Suboptimal clinical evaluation can result in missed diagnoses and excess
      morbidity and mortality. We estimate the sensitivity of pneumonia diagnosis and
      investigate its determinants among children in Malawi. Methods: Data were
      obtained from the 2013-2014 Service Provision Assessment survey, a census of
      health facilities in Malawi that included direct observation of care and re
      examination of children by trained observers. We calculated sensitivity of
      pneumonia diagnosis and used multilevel log-binomial regression to assess factors
      associated with diagnostic sensitivity. Results: 3136 clinical visits for
      children 2-59 months old were observed at 742 health facilities. Healthcare
      workers completed an average of 30% (SD 13%) of IMCI guidelines in each
      encounter. 573 children met the IMCI criteria for pneumonia; 118 (21%) were
      correctly diagnosed. Advanced practice clinicians were more likely than other
      providers to diagnose pneumonia correctly (adjusted relative risk 2.00, 95% CI
      1.21 to 3.29). Clinical quality was strongly associated with correct diagnosis:
      sensitivity was 23% in providers at the 75th percentile for guideline adherence
      compared with 14% for those at the 25th percentile. Contextual factors, facility
      structural readiness, and training or supervision were not associated with
      sensitivity. Conclusions: Care quality for Malawian children is poor, with low
      guideline adherence and missed diagnosis for four of five children with
      pneumonia. Better sensitivity is associated with provider type and higher
      adherence to IMCI. Existing interventions such as training and supportive
      supervision are associated with higher guideline adherence, but are insufficient
      to meaningfully improve sensitivity. Innovative and scalable quality improvement
      interventions are needed to strengthen health systems and reduce avoidable child
      mortality.

PMID- 29662689
TI  - Supporting the development of a health benefits package in Malawi.
AB  - Malawi, like many low-income and middle-income countries, has used health
      benefits packages (HBPs) to allocate scarce resources to key healthcare
      interventions. With no widely accepted method for their development, HBPs often
      promise more than can be delivered, given available resources. An analytical
      framework is developed to guide the design of HBPs that can identify the
      potential value of including and implementing different interventions. It
      provides a basis for informing meaningful discussions between governments, donors
      and other stakeholders around the trade-offs implicit in package design. Metrics
      of value, founded on an understanding of the health opportunity costs of the
      choices faced, are used to quantify the scale of the potential net health impact
      (net disability adjusted life years averted) or the amount of additional
      healthcare resources that would be required to deliver similar net health impacts
      with existing interventions (the financial value to the healthcare system). The
      framework can be applied to answer key questions around, for example: the
      appropriate scale of the HBP; which interventions represent 'best buys' and
      should be prioritised; where investments in scaling up interventions and health
      system strengthening should be made; whether the package should be expanded;
      costs of the conditionalities of donor funding and how objectives beyond
      improving population health can be considered. This is illustrated using data
      from Malawi. The framework was successfully applied to inform the HBP in Malawi,
      as a core component of the country's Health Sector Strategic Plan II 2017-2022.

PMID- 29662690
TI  - Geographic coverage of demographic surveillance systems for characterising the
      drivers of childhood mortality in sub-Saharan Africa.
AB  - A major focus of international health and development goals is the reduction of
      mortality rates in children under 5 years of age. Achieving this requires
      understanding the drivers of mortality and how they vary geographically to
      facilitate the targeting and prioritisation of appropriate interventions. Much of
      our knowledge on the causes of, and trends in, childhood mortality come from
      longitudinal demographic surveillance sites, with a renewed focus recently on the
      establishment and growth of networks of sites from which standardised outputs can
      facilitate broader understanding of processes. To ensure that the collective
      outputs from surveillance sites can be used to derive a comprehensive
      understanding and monitoring system for driving policy on tackling childhood
      mortality, confidence is needed that existing and planned networks of sites are
      providing a reliable and representative picture of the geographical variation in
      factors associated with mortality. Here, we assembled subnational data on
      childhood mortality as well as key factors known to be associated with it from
      household surveys in 27 sub-Saharan African countries. We then mapped the
      locations of existing longitudinal demographic surveillance sites to assess the
      extent of current coverage of the range of factors, identifying where gaps exist.
      The results highlight regions with unique combinations of factors associated with
      childhood mortality that are poorly represented by the current distribution of
      sites, such as southern Mali, central Nigeria and southern Zambia. Finally, we
      determined where the establishment of new surveillance systems could improve
      coverage.

PMID- 29662691
TI  - Poverty reduction and equity benefits of introducing or scaling up measles,
      rotavirus and pneumococcal vaccines in low-income and middle-income countries: a
      modelling study.
AB  - Introduction: Beyond their impact on health, vaccines can lead to large economic
      benefits. While most economic evaluations of vaccines have focused on the health
      impact of vaccines at a national scale, it is critical to understand how their
      impact is distributed along population subgroups. Methods: We build a financial
      risk protection model to evaluate the impact of immunisation against measles,
      severe pneumococcal disease and severe rotavirus for birth cohorts vaccinated
      over 2016-2030 for three scenarios in 41 Gavi-eligible countries: no
      immunisation, current immunisation coverage forecasts and the current
      immunisation coverage enhanced with funding support. We distribute modelled
      disease cases per socioeconomic group and derive the number of cases of: (1)
      catastrophic health costs (CHCs) and (2) medical impoverishment. Results: In the
      absence of any vaccine coverage, the number of CHC cases attributable to measles,
      severe pneumococcal disease and severe rotavirus would be approximately 18.9
      million, 6.6 million and 2.2 million, respectively. Expanding vaccine coverage
      would reduce this number by up to 90%, 30% and 40% in each case. More
      importantly, we find a higher share of CHC incidence among the poorest quintiles
      who consequently benefit more from vaccine expansion. Conclusion: Our findings
      contribute to the understanding of how vaccines can have a broad economic impact.
      In particular, we find that immunisation programmes can reduce the proportion of
      households facing catastrophic payments from out-of-pocket health expenses,
      mainly in lower socioeconomic groups. Thus, vaccines could have an important role
      in poverty reduction.

PMID- 29662692
TI  - Strengthening health district management competencies in Ghana, Tanzania and
      Uganda: lessons from using action research to improve health workforce
      performance.
AB  - Background: To achieve Universal Health Coverage (UHC), more health workers are
      needed; also critical is supporting optimal performance of existing staff.
      Integrated human resource management (HRM) strategies, complemented by other
      health systems strategies, are needed to improve health workforce performance,
      which is possible at district level in decentralised contexts. To strengthen the
      capacity of district management teams to develop and implement workplans
      containing integrated strategies for workforce performance improvement, we
      introduced an action-research-based management strengthening intervention (MSI).
      This consisted of two workshops, follow-up by facilitators and meetings between
      participating districts. Although often used in the health sector, there is
      little evaluation of this approach in middle-income and low-income country
      contexts. The MSI was tested in three districts in Ghana, Tanzania and Uganda.
      This paper reports on the appropriateness of the MSI to the contexts and its
      effects. Methods: Documentary evidence (workshop reports, workplans, diaries,
      follow-up visit reports) was collected throughout the implementation of the MSI
      in each district and interviews (50) and focus-group discussions (6) were
      conducted with managers at the end of the MSI. The findings were analysed using
      Kirkpatrick's evaluation framework to identify effects at different levels.
      Findings: The MSI was appropriate to the needs and work patterns of District
      Health Management Teams (DHMTs) in all contexts. DHMT members improved management
      competencies for problem analysis, prioritisation and integrated HRM and health
      systems strategy development. They learnt how to refine plans as more information
      became available and the importance of monitoring implementation. The MSI
      produced changes in team behaviours and confidence. There were positive results
      regarding workforce performance or service delivery; these would increase with
      repetition of the MSI. Conclusions: The MSI is appropriate to the contexts where
      tested and can improve staff performance. However, for significant impact on
      service delivery and UHC, a method of scaling up and sustaining the MSI is
      required.

PMID- 29662693
TI  - Paediatric and obstetric outcomes at a faith-based hospital during the 100-day
      public sector physician strike in Kenya.
AB  - Published reviews of national physician strikes have shown a reduction in patient
      mortality. From 5 December 2016 until 14 March 2017, Kenyan physicians in the
      public sector went on strike leaving only private (not-for-profit and for-profit)
      hospitals able to offer physician care. We report on our experience at AIC-Kijabe
      Hospital, a not-for-profit, faith-based Kenyan hospital, before, during and after
      the 100-day strike was completed by examining patient admissions and deaths in
      the time periods before, during and after the strike. The volume of patients
      increased and exceeded the hospital's ability to respond to needs. There were
      substantial increases in sick newborn admissions during this time frame and an
      additional ward was opened to respond to this need. Increased need occurred
      across all services but staffing and space limited ability to respond to
      increased demand. There were increases in deaths during the strike period across
      the paediatric medical, newborn, paediatric surgical and obstetric units with an
      OR (95% CI) of death of 3.9 (95% CI 2.3 to 6.4), 4.1 (95% CI 2.4 to 7.1), 7.9
      (95% CI 3.2 to 20) and 3.2 (95% CI 0.39 to 27), respectively. Increased mortality
      across paediatric and obstetrical services at AIC-Kijabe Hospital correlated with
      the crippling of healthcare delivery in the public sector during the national
      physicians' strike in Kenya.

PMID- 29662694
TI  - From the battlefield to the bedroom: a multilevel analysis of the links between
      political conflict and intimate partner violence in Liberia.
AB  - Objectives: Assess the link between levels of armed conflict and postconflict
      intimate partner violence (IPV) experienced by women in Liberia. Methods: Armed
      Conflict Location and Event Data Project data were used to measure conflict
      related fatalities in districts in Liberia during the country's civil war from
      1999 to 2003. These data were linked to individual-level data from the 2007
      Demographic and Health Survey, including past-year IPV. Multilevel logistic
      models accounting for the clustering of women within districts evaluated the
      relationship of conflict fatalities with postconflict past-year IPV. Additional
      conflict measures, including conflict events and cumulative years of conflict,
      were assessed. Results: After adjusting for individual-level characteristics
      correlated with IPV, residence in a conflict fatality-affected district was
      associated with a 50% increase in risk of IPV (adjusted OR (aOR): 1.55, 95% CI
      1.26 to 1.92). Women living in a district that experienced 4-5 cumulative years
      of conflict were also more likely to experience IPV (aOR 1.88, 95% CI 1.29 to
      2.75). Conclusion: Residing in a conflict-affected district even 5 years after
      conflict was associated with postconflict IPV. Policy implications: Recognising
      and preventing postconflict IPV violence is important to support long-term
      recovery in postconflict settings.

PMID- 29662695
TI  - Impact of a health system strengthening intervention on maternal and child health
      outputs and outcomes in rural Rwanda 2005-2010.
AB  - Introduction: Although Rwanda's health system underwent major reforms and
      improvements after the 1994 Genocide, the health system and population health in
      the southeast lagged behind other areas. In 2005, Partners In Health and the
      Rwandan Ministry of Health began a health system strengthening intervention in
      this region. We evaluate potential impacts of the intervention on maternal and
      child health indicators. Methods: Combining results from the 2005 and 2010
      Demographic and Health Surveys with those from a supplemental 2010 survey, we
      compared changes in health system output indicators and population health
      outcomes between 2005 and 2010 as reported by women living in the intervention
      area with those reported by the pooled population of women from all other rural
      areas of the country, controlling for potential confounding by economic and
      demographic variables. Results: Overall health system coverage improved similarly
      in the comparison groups between 2005 and 2010, with an indicator of composite
      coverage of child health interventions increasing from 57.9% to 75.0% in the
      intervention area and from 58.7% to 73.8% in the other rural areas. Under-five
      mortality declined by an annual rate of 12.8% in the intervention area, from
      229.8 to 83.2 deaths per 1000 live births, and by 8.9% in other rural areas, from
      157.7 to 75.8 deaths per 1000 live births. Improvements were most marked among
      the poorest households. Conclusion: We observed dramatic improvements in
      population health outcomes including under-five mortality between 2005 and 2010
      in rural Rwanda generally and in the intervention area specifically.

PMID- 29662696
TI  - Bias in patient satisfaction surveys: a threat to measuring healthcare quality.
AB  - Patient satisfaction surveys are an increasingly common element of efforts to
      evaluate the quality of healthcare. Many patient satisfaction surveys in
      low/middle-income countries frame statements positively and invite patients to
      agree or disagree, so that positive responses may reflect either true
      satisfaction or bias induced by the positive framing. In an experiment with more
      than 2200 patients in Nigeria, we distinguish between actual satisfaction and
      survey biases. Patients randomly assigned to receive negatively framed statements
      expressed significantly lower levels of satisfaction (87%) than patients
      receiving the standard positively framed statements (95%-p<0.001). Depending on
      the question, the effect is as high as a 19 percentage point drop (p<0.001).
      Thus, high reported patient satisfaction likely overstates the quality of health
      services. Providers and policymakers wishing to gauge the quality of care will
      need to avoid framing that induces bias and to complement patient satisfaction
      measures with more objective measures of quality.

PMID- 29662697
TI  - Supporting capacity for research on malaria in Africa.
AB  - Substantial progress has been made in the control of malaria in Africa but much
      remains to be done before malaria elimination on the continent can be achieved.
      Further progress can be made by enhancing uptake of existing control tools but,
      in high transmission areas, additional tools will be needed. Development and
      evaluation of these new tools will require a substantial cadre of African
      scientists well trained in many different disciplines. This paper describes the
      activities undertaken by the Malaria Capacity Development Consortium (MCDC) to
      support the careers of PhD students and postdoctoral fellows undertaking research
      on malaria at five African universities. A systematic assessment of constraints
      on PhD training and research support systems was undertaken at each partner
      African university at the beginning of the programme and many of these
      constraints were remedied. The success of the programme is shown by the fact that
      18 of the 21 PhD students recruited to the programme completed their theses
      successfully within a 4-year period and that all 27 scientists recruited to the
      postdoctoral programme were still working in Africa on its completion. The work
      of the consortium will be continued through Career Development Groups established
      at each partner university and at an affiliated institution at the University of
      Nairobi and through the Developing Excellence in Leadership, Training and Science
      award from the Wellcome Trust made to one of the African partners. Lessons learnt
      during the MCDC programme may help the planning and execution of other research
      capacity development programmes in Africa.

PMID- 29662698
TI  - Not just a number: examining coverage and content of antenatal care in low-income
      and middle-income countries.
AB  - Introduction: Antenatal care (ANC) provides a critical opportunity for women and
      babies to benefit from good-quality maternal care. Using 10 countries as an
      illustrative analysis, we described ANC coverage (number of visits and timing of
      first visit) and operationalised indicators for content of care as available in
      population surveys, and examined how these two approaches are related. Methods:
      We used the most recent Demographic and Health Survey to analyse ANC related to
      women's most recent live birth up to 3 years preceding the survey. Content of
      care was assessed using six components routinely measured across all countries,
      and a further one to eight additional country-specific components. We estimated
      the percentage of women in need of ANC, and using ANC, who received each
      component, the six routine components and all components. Results: In all 10
      countries, the majority of women in need of ANC reported 1+ ANC visits and over
      two-fifths reported 4+ visits. Receipt of the six routine components varied
      widely; blood pressure measurement was the most commonly reported component, and
      urine test and information on complications the least. Among the subset of women
      starting ANC in the first trimester and receiving 4+ visits, the percentage
      receiving all six routinely measured ANC components was low, ranging from 10%
      (Jordan) to around 50% in Nigeria, Nepal, Colombia and Haiti. Conclusion: Our
      findings suggest that even among women with patterns of care that complied with
      global recommendations, the content of care was poor. Efficient and effective
      action to improve care quality relies on development of suitable content of care
      indicators.

PMID- 29662699
TI  - Quality of WHO guidelines on snakebite: the neglect continues.

PMID- 29662700
TI  - Capzb2 PROTEIN EXPRESSION IN THE BRAINS OF PATIENTS DIAGNOSED WITH ALZHEIMER'S
      DISEASE AND HUNTINGTON'S DISEASE.
AB  - The silencing of actin capping protein beta2, Capzb2, by RNAi in developing
      cultured neurons results in short, dystrophic neurites reminiscent of
      cytoskeletal changes seen in diverse neurodegenerative diseases, including
      Alzheimer's disease (AD) and Huntington's disease (HD). Actin and tubulin are two
      major cytoskeletal proteins indispensable for normal neurite development and
      regenerative responses to injury and neurodegenerative stimuli. We have
      previously shown that Capzb2 binds tubulin and, in the presence of microtubule-
      associated protein tau, affects microtubule polymerization necessary for neurite
      outgrowth and normal growth cone morphology. Accordingly, Capzb2 silencing in
      hippocampal neurons results in short neurites with abnormal growth cones.
      Decreased neurite length is found in both AD and HD. In the first step towards
      uncovering the possible role of Capzb2 in these diseases, we studied Capzb2
      protein expression in the postmortem brains of AD and HD patients. To determine
      whether disease-specific changes in Capzb2 protein accompany the progression of
      neurodegeneration, we performed Western Blot analysis of prefrontal cortices
      (PFC) and hippocampi (HPC) in AD patients and of PFC and heads of caudate nuclei
      (HCN) in HD patients. Our results show disease- and area-specific dynamics in the
      levels of Capzb2 protein expression in the progressive stages of AD and HD.

PMID- 29662701
TI  - The Arcuate Fasciculus Network and Verbal Deficits in Psychosis.
AB  - Background: Verbal learning (VL) and fluency (VF) are prominent cognitive
      deficits in psychosis, of which the precise neuroanatomical contributions are not
      fully understood. We investigated the arcuate fasciculus (AF) and its associated
      cortical regions to identify structural abnormalities contributing to these
      verbal impairments in early stages of psychotic illness. Methods: Twenty-six
      individuals with recent-onset psychosis and 27 healthy controls underwent
      cognitive testing (MATRICS Consensus Cognitive Battery) and structural/diffusion
      weighted MRI. Bilaterally, AF anisotropy and cortical thickness, surface area and
      volume of seven cortical regions were investigated in relation to VL and VF
      performance in both groups. Results: Reduced right superior temporal gyrus
      surface area and volume related to better VF in controls. In psychosis, greater
      right pars opercularis volume and reduced left lateralization of this region
      related to better VL, while greater right long AF fractional anisotropy and right
      pars orbitalis volume related to better VF, these findings not present in
      controls. Psychosis had reduced right pars orbitalis thickness compared to
      controls. Conclusion: Anatomical substrates for normal processing of VL and VF
      appear altered in recent-onset psychosis. A possible aberrant role of the right
      hemisphere arcuate fasciculus and fronto-temporal cortical regions in psychosis
      may contribute to deficits in VL and VF.

PMID- 29662702
TI  - The Ipsilateral Vestibulothalamic Tract in the Human Brain.
AB  - Although there are a few studies of portions of the vestibular system such as the
      vestibulocerebellar tract and the neural connectivity of the vestibular nuclei
      (VN), no study of the ipsilateral vestibulothalamic tract (VTT) (originating from
      the VN and mainly connecting to the lateral thalami nuclei) has been reported. In
      the current study, using diffusion tensor tractography (DTT), we investigate the
      reconstruction method and characteristics of the ipsilateral VTT in normal
      subjects. Thirty-three subjects were recruited for this study. For the
      ipsilateral VTT, the seed region of interest (ROI) was placed on the VN, which
      was isolated on the FA map using adjacent structures as follows: the reticular
      formation (anterior boundary), posterior margin of medulla and pons (posterior
      boundary), medial lemniscus (medial boundary) and restiform body (lateral
      boundary). The target ROI was placed at the lateral thalamic nuclei using known
      anatomical locations. The DTT parameters of the ipsilateral VTT were measured.
      The ipsilateral VTTs that originated from the vestibular nuclei ascended postero
      laterally to the upper pons and antero-medially to the upper midbrain via the
      medial longitudinal fasciculus, and terminated the lateral thalamic nuclei. No
      significant differences were observed in DTT parameters of the ipsilateral VTT
      between the right and left hemispheres (p > 0.05). Using DTT, we reconstructed
      the ipsilateral VTT and observed the anatomical characteristics of the
      ipsilateral VTT in normal subjects. We believe that the methodology and results
      in this study could be helpful to researchers and clinicians in this field.

PMID- 29662703
TI  - Aortic Dissection Presenting as Acute Pancreatitis: Suspecting the Unexpected.
AB  - Aortic dissection is a life-threatening condition in which the inner layer of the
      aorta tears. Blood surges through the tear, causing the inner and middle layers
      of the aorta to separate (dissect). It is considered a medical emergency. We
      report a case of a healthy 56-year-old male who presented to the emergency room
      with sudden onset of epigastric pain radiating to his back. His blood pressure
      was 167/91 mmHg, equal in both arms. His lipase was elevated at 1258 U/L, and he
      was clinically diagnosed with acute pancreatitis (AP). He denied any alcohol
      consumption, had no evidence for gallstones, and had normal triglyceride level.
      Two days later, he endorsed new suprapubic tenderness radiating to his scrotum,
      along with worsening epigastric pain. A MRCP demonstrated evidence of an aortic
      dissection (AD). CT angiography demonstrated a Stanford type B AD extending into
      the proximal common iliac arteries. His aortic dissection was managed medically
      with rapid blood pressure control. The patient had excellent recovery and was
      discharged home without any surgical intervention.

PMID- 29662704
TI  - Diagnosis of Anomalous Origin of the Left Coronary Artery from the Pulmonary
      Artery with Echocardiography and Digital Subtraction Angiography.
AB  - Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA)
      is a common coronary artery anomaly associated with high mortality and may lead
      to sudden death if left unrecognized and untreated. This report describes an 8
      year-old female who had cardiac murmur but with no clinical symptoms.
      Electrocardiogram (ECG) was normal, but echocardiography made the diagnosis of
      ALCAPA. Digital subtraction angiography (DSA) with cardiac catheterization
      angiography (CAG) confirmed the diagnosis, and finally, the patient received
      surgery. This case demonstrates that echocardiography is a sensitive and
      convenient technique for establishing the initial diagnosis of ALCAPA in both
      symptomatic and asymptomatic patients.

PMID- 29662705
TI  - Aortitis as a Rare Cause of Aortic Aneurysm and Valve Regurgitation: Is Repair
      Precluded?
AB  - Aortitis is an infrequent cause of aortic root dilatation and aortic valve
      regurgitation. Valve-sparing procedures have been proposed, but there is not
      clear evidence of which is the treatment of choice. We report the case of a 38
      year-old pregnant lady with a diagnosis of idiopathic aortitis associated with
      aortic root aneurysm and severe aortic valve regurgitation.

PMID- 29662706
TI  - Assessment of Occlusal Function in a Patient with an Angle Class I Spaced Dental
      Arch with Periodontal Disease Using a Brux Checker.
AB  - Comprehensive and appropriate occlusion reconstruction therapy is necessary for
      orthodontic treatment of adult patients with malocclusion with periodontal
      disease associated with occlusal trauma. We report the case of a patient with
      extensive moderate chronic periodontitis associated with occlusal trauma. The
      patient was diagnosed with extensive moderate chronic periodontitis associated
      with occlusal trauma and underwent thorough treatment for periodontal disease,
      oral management, and 20 months of orthodontic therapy. Moreover, reconstructed
      occlusion was performed to evaluate occlusal trauma for visualization using Brux
      Checker (BC) analysis before and after active orthodontic treatment. The patient
      acquired stable anterior guidance and a functional occlusal relationship. BC
      findings revealed weakening of the functional contact between the lateral
      occlusal force of the dentition and the front teeth and alveolar bone
      regeneration. The laminar dura became clearer, and the periodontal tissue
      improved. Our results suggest that assessment of occlusion function using BC
      analysis and periodontal examination was effective in enabling occlusal treatment
      goal clarification through orthodontic treatment in case of periodontal disease
      associated with occlusal trauma.

PMID- 29662707
TI  - Percutaneous Ethanol Injection in Combination with Laser Ablation for a 100 ml
      Partially Cystic Thyroid Nodule.
AB  - Until nonsurgical techniques like laser ablation (LA) or radiofrequency became
      available, patients suffering from large nodules with compressive symptoms were
      addressed to surgery. We describe the case of a 59-year-old woman with a large,
      partially cystic thyroid nodule having a volume of about 100 ml. As the patient
      refused surgery, despite her constant local discomfort, such large partially
      cystic nodule underwent several percutaneous ethanol injections (PEI) and then
      was submitted to LA. The combination of these two procedures allowed firstly
      complete disappearance of the cystic component and secondly a significant
      reduction of thyroid nodule, which finally measured 17 ml in volume (82%
      reduction compared to baseline). This case demonstrates that even in very large
      partially cystic nodules LA preceded by PEI represents a valid alternative to
      surgery.

PMID- 29662708
TI  - Emergency peripartum hysterectomy in the Dubai health system: A fifteen year
      experience.
AB  - Objective: To determine the incidence, demographic data, risk factors,
      indications, outcome and complications of emergency peripartum hysterectomy (EPH)
      performed in two major tertiary care hospitals in Dubai, and to compare the
      results with the literature. Materials and Methods: The records of all women who
      underwent EPH from January 2000 to December 2015 in two major tertiary care
      hospitals in Dubai were accessed and reviewed. Maternal characteristics,
      hysterectomy indications, outcomes, and postoperative complications were recorded
      using descriptive statistics to describe the cohort. Results: There were 79 EPH
      out of 168.293 deliveries, a rate of 0.47/1000 deliveries. The most common
      indications for hysterectomy were abnormal placentation (previa and/or accreta)
      and uterine atony. The majority of hysterectomies were subtotal (70%). The
      complications were dominated by massive transfusion, urinary tract injuries, one
      case of maternal death, and one case of neonatal death. Conclusion: The main
      indication for EPH was abnormal placentation in scarred uterus and uterine atony.
      The major method of prevention of EPH is to assess women's risks and to reduce
      the number of cesarean section deliveries, by limiting the rate of primary
      cesareans. This is challenging in the United Arab Emirates (UAE) where the
      culture is for high gravidity and high parity. Recommendations to act to reduce
      primary and repeated cesareans should be included on the national agenda in UAE.

PMID- 29662709
TI  - The impact of different 75 g oral glucose tolerance test target ranges within
      normal limits on neonatal outcomes: A validation study.
AB  - Objective: To investigate the impact of different 75 g glucose tolerance test
      (OGTT) target ranges within normal limits on neonatal outcomes, thus to
      investigate the validity of 75 g OGTT thresholds. Materials and Methods: The
      normal 1-hour and 2-hour ranges of 75 g OGTT levels of 110 pregnant women with no
      gestational diabetes mellitus (GDM) were further divided into three different sub
      groups; for the 1 hour as group 1 (<120 mg/dL), group 2 (120-140 mg/dL), group 3
      (>140 mg/dL) and for the 2 hour as group 1 (<120 mg/dL), group 2 (120-135 mg/dL),
      and group 3 (>135 mg/dL). Results: For the 1-hour results, there was no
      statistically significant difference between groups in terms of age, body mass
      index, multiparity, neonatal hypoglycemia, hyperbilirubinemia, neonatal intensive
      care unit admission, birth weight, and LGT rates; however, the rate of small-for
      gestational-age (SGA) infants was significantly higher in group 2 compared with
      those in group 3. For the 2-hour results, statistically similar results were
      found between the groups. Conclusion: A 2-hour 75 g OGTT has reliable threshold
      values for GDM screening. However, because there are still adverse neonatal
      outcomes in women with OGTT results below the current thresholds and the number
      of SGA fetuses is higher in the glucose range 120-140 mg/dL of the first hour,
      the validity of the 75 g OGTT thresholds still needs further investigation.

PMID- 29662710
TI  - Natural cycle versus artificial cycle in frozen-thawed embryo transfer: A
      randomized prospective trial.
AB  - Objective: To investigate whether there was a difference in pregnancy outcomes
      between modified natural cycle frozen-thawed embryo transfer (NC-FET) cycles and
      artificial cycles (AC)-FET in women who all had regular menstrual cycles.
      Materials and Methods: One hundred seventy patients who met the inclusion
      criteria and had at least two cryopreserved embryos were included in a
      prospective randomized controlled trial. Eighty-five patients were randomized
      based on Bernoulli distribution into the following two groups: 1) Modified NC-FET
      using human chorionic gonadotropin for ovulation induction and 2) AC-FET, in
      which endometrial timing was programmed with estrogen and progesterone. The main
      studied outcome measure was the clinical pregnancy rate per cycle. Results: No
      significant differences were found between the two groups with regard to the
      chemical, clinical, and ongoing pregnancy rates (48.2% vs 45.9%, p>0.05; 38.9% vs
      35.3%, p>0.05; and 37.6% vs 34.1%, p>0.05, respectively), as well as the live
      birth or miscarriage rates per cycle (35.3% vs 31.8%, p>0.05; and 1.2% vs 1.2%,
      p>0.05, respectively). Conclusion: These findings suggest that although both FET
      protocols are equally effective in terms of pregnancy outcomes in women with
      regular menstrual cycles, NC-FET is more favorable because it requires no
      medication, has no adverse events, and has a significant cost reduction.

PMID- 29662711
TI  - Segmental duplication-quantitative fluorescent-polymerase chain reaction: An
      approach for the diagnosis of Down syndrome in India.
AB  - Objective: Early detection of high-risk pregnancies for Down syndrome (DS) is the
      main target of offering prenatal diagnosis. Segmental duplication-quantitative
      fluorescent-polymerase chain reaction (SD-QF-PCR) can be used as an alternative
      method for prenatal diagnosis of DS. SD-QF-PCR involves SD sequences between the
      test and control chromosomes to detect aneuploidies. SD are two similar sequences
      with different fragment lengths, located on two different chromosomes. When these
      SD regions are amplified, the peak ratio between the two different chromosomes
      remains as 0.9 to 1.1 and the trisomy 21 results in the ratio of 1.4 to 1.6.
      Materials and Methods: In this study, we applied SD-QF-PCR to detect the presence
      of trisomy 21 in 60 age-matched controls and 60 DS samples. The PCR amplification
      of SD regions is performed using a single pair of fluorescent-labelled primers,
      the peak ratio between the two different chromosome regions are evaluated.
      Results: All sixty control samples showed the peaks to range from 0.9 to 1.1,
      which was suggestive of normal samples, and peaks of 65 DS samples ranged from
      1.4 to 1.6, which suggested the presence of trisomy 21. Conclusion: Segmental
      duplication quantitative fluorescent PCR is a sensitive and rapid aneuploidy
      detection technique and hence can be used as a standalone test to detect trisomy
      21 as well as other aneuploidies.

PMID- 29662712
TI  - Do Syrian refugees have increased risk for worser pregnancy outcomes? Results of
      a tertiary center in Istanbul.
AB  - Objective: To compare obstetric and perinatal outcomes of Syrian refugee
      pregnants and Turkish counterparts who gave birth at a tertiary center in
      Istanbul. Materials and Methods: A retrospective study including the birth
      records of 704 Syrian refugees and 744 Turkish pregnant women between January
      2016 and May 2017 were analyzed. Demographic data, obstetric and neonatal
      outcomes were compared. The primary aims of this study were to evaluate the
      pregnancy outcomes and cesarean rates between the groups. The secondary outcomes
      were the use of antenatal vitamin supplementation, hemoglobin-hematocrit values,
      and maternal complications. Results: Our results showed that the use of folic
      acid and iron supplementation rates during pregnancy were similar between the
      groups (folic acid supplementation 8.1% vs 6.5%, p=0.264; iron supplementation
      20.7% vs 19.6%, p=0.125; respectively for Turkish women and Syrian refugees).
      Cesarean rates were significantly higher for Turkish patients than in Syrian
      refugees (42.7% vs 32.7%; p<0.05). Gestational age at delivery was significantly
      higher among Turkish women when compared with Syrian refugees (37.7+/-2.3 vs
      36.4+/-2.3 weeks, p<0.05), but there was no significant difference regarding the
      birtweights' of the newborns (3134 g vs 3066 g for Turkish women and Syrian
      refugees, respectively, p=0.105). Although obstetric complications were seen more
      often in Syrian refugees, it did not reach statistical difference (9.7% vs 8.1%,
      respectively, p=0.285). Conclusion: Syrian refugees use antenatal vitamin
      supplementations at similar rates to Turkish citizens and obstetric and perinatal
      outcomes are similar between the groups.

PMID- 29662713
TI  - Are the skin scar characteristics and closure of the parietal peritoneum
      associated with pelvic adhesions?
AB  - Objective: To assess whether the abdominal scar characteristics and closure of
      the peritoneum were associated with pelvic adhesions. Materials and Methods:
      Patients who had undergone cesarean section between December 2015 and February
      2016 were assessed prospectively in terms of age, gravida, body mass index,
      number of living children, number of cesarean sections, time passed since the
      last cesarean section, closure status of the peritoneum in the last cesarean
      section, presence of other diseases, smoking status, location of incision in the
      abdomen (medial, pfannenstiel) scar dimensions (length, width), scar status with
      respect to skin (hypertrophic, flat, depressive), scar color [color change/no
      color change (hyperpigmented/hypopigmented)], adhesion of bowel-omentum-uterus,
      omentum-anterior abdominal wall, uterus-anterior abdominal wall, uterus-bladder,
      bladder-anterior abdominal wall, fixed uterus, and uterus-omentum-anterior
      abdominal wall in abdominal exploration. Results: One hundred five pregnant women
      who had undergone previous ceserean section surgery by the same physician, were
      at least in their 30th gestational week, had surgery notes about their previous
      operation, and had no chronic diseases were included in the study. Age, gravida,
      body mass index, number of children, number of cesarean sections, time passed
      since the previous cesarean section, closure/non-closure of peritoneum in the
      previous cesarean section, and smoking status had no effect on pelvic adhesions.
      Intraabdominal adhesion was not found to be associated with scar length [odds
      ratio (OR): 1.54, 95% confidence interval (CI): 1.1-2.2; p=0.02], depressive scar
      (OR: 9.3, 95% CI: 3.2-27.2; p<0.001), or hypopigmented scar [OR: 0.01, 95% CI:
      0.003-0.11; p<0.001]. Conclusion: Adhesions following surgical operations are of
      great importance due to complications for the patient, complications in
      relaparotomy, and high costs. Depressive and hypopigmented abdominal scars may be
      associated with pelvic adhesions. We believe that closure or non-closure of the
      parietal peritoneum is not associated with pelvic adhesions.

PMID- 29662714
TI  - Post-cesarean scar endometriosis.
AB  - Objective: Endometriosis is seen in women during their reproductive period, where
      stromal tissue and functional endometrial glands of the uterus are observed
      outside the uterine cavity. In this study, we aimed to identify the clinical
      characteristics of our patients who underwent surgery with scar endometriosis and
      to discuss the surgical results in light of the literature. Materials and
      Methods: A total of 24 patients who underwent surgery and diagnosed as having
      endometriosis as the result of a pathologic examination were retrospectively
      evaluated. Results: The mean age of the patients was 31 years. Thirteen presented
      to general surgery and 11 presented to gynecology outpatient clinics. The pain
      was cyclical in 19 patients. There was history of cesarean section in 9 patients,
      twice in 12, and 3 times in three patients. The mean diameter was 39.1 mm on
      ultrasound, and 37.5 mm on magnetic resonance imaging. Endometriosis was on the
      left side of the incisions in 13, whereas it was on the right in 11. The mean
      weight of the lesions was 61.6 grams. Conclusion: The occurrence of endometriosis
      is supported by the iatrogenic implantation theory. In the event of a mass in the
      abdominal wall, previous obstetric and gynecologic operations and a history of a
      painful mass during menstruation periods must be questioned. In the treatment of
      scar endometriosis, excision is required by obtaining secure margins. If
      diagnosis can be established preoperatively, unnecessary surgeries can prevented.

PMID- 29662715
TI  - The effect of the pooling method on the live birth rate in poor ovarian
      responders according to the Bologna criteria.
AB  - Objective: Pooling is an alternative method to achieve in vitro fertilization
      outcomes. This study was to investigate the effect of pooling method on pregnancy
      outcomes in poor responder patients according to Bologna criteria. Materials and
      Methods: Two hundred-fifty five poor responder patients were enrolled in this
      study. Pooling embryo transfer (ET) group had 110 and fresh ET group had 145
      patients. Results: Although, age was similar between both treatment groups
      (p=0.31), antral follicle count (p<0.001), total number of retrieved oocyte
      (p<0.001), total metaphase II oocyte count (p<0.001), number of stimulation
      cycles (p<0.001), were significantly different between the groups. The day of ET
      were similiar between two groups (p=0.72) but the number of ET procedure was
      significantly higher in pooling ET group compared to fresh ET (p<0.001). Positive
      pregnancy test [35/110 (32%) vs 53/145 (37%)] (p=0.43) and clinical pregnacy
      rates [31/110 (28%) vs 49/145 (34%)] (p=0.33) were similar between groups,
      whereas, implantation [31/191 (16%) vs 49/198 (25%)] (p=0.03) and live birth
      rates [15/110 (14%) vs 36/145 (25%)] (p=0.04) were significantly higher in fresh
      ET group. Despite that, abortion rates were significantly higher in pooling ET
      group [16/31 (52%) vs 13/49 (27%)] (p=0.04). Binary logistic regression analyese
      has revealed no effect of variables on live birth rates. Conclusion: Even though,
      pooling strategy seems to have a slight positive effect on pregnancy outcomes,
      there is no benefical effect on live birth rates. Furthermore, this strategy is
      increasing the abortion rates in parallel with clinical pregnancy rates.

PMID- 29662716
TI  - Social stigma and familial attitudes related to infertility.
AB  - Objective: To determine the perceived social stigma and familial attitides and
      perception of sexuality in infertile couples attending infertility clinics.
      Materials and Methods: Infertile couples attending infertility clinics between
      the years of 2014 and 2015 were requested to complete detailed evaluation forms
      including questions related to the social stigma on their infertility, their
      familial attitudes, and perception of sexuality. Any partner of the infertile
      couple accepting to enroll in the study was given the evaluation forms. Their
      scores related to answers and demographics, and parameters related to infertility
      were analyzed. Results: A total 598 partners of infertile couples enrolled in the
      study, 58% represented 177 couples. Their infertility was primary in 98.3% and
      the duration of marriage and infertility was 9.81+/-5.58 and 9.76+/-5.53 years,
      respectively. The perception of social exclusion was present in 38% (p<0.001) of
      infertile couple, which was more significantly pronounced in female partners
      (p=0.013). Fifteen percent of the infertile couples thought themselves as
      isolated in public and losing value in public (p<0.001). However, sixty percent
      of infertile couples thought that they would achieve a notable place in community
      after having a baby (p<0.001). Infertility was accepted as a reason of divorce in
      only 13% of infertile couples (p<0.001). The majority of perticipnats,
      irrespective of sex, rejected that infertile women or men lost sexual appeal
      (86%; p<0.001). Conclusions: There is significant effect of infertility on
      familial attitudes and perception of sexuality of infertile couples.
      Unfortunately, there is significant negative social stigma on infertile couples.

PMID- 29662718
TI  - Is the measurement of the size of uterine lesions with positron emission
      tomography consistent in pre- and postmenopausal periods in endometrioid-type
      endometrial cancer?
AB  - Objective: We aimed to investigate the correlation of the size and volume of
      uterine tumors obtained using positron emission tomography/computed tomography
      (PET/CT) and pathology specimens in patients with endometrioid-type endometrial
      cancer (EEC) in the premenopausal period, and to compare the results with those
      of postmenopausal women. In the premenopausal period, the endometrium uses more
      glucose than in the postmenopausal period. Therefore, the measurement of uterine
      tumor size using PET/CT in the premenopausal period may normally be different.
      Materials and Methods: In this retrospective study, we reviewed the records of
      patients who were diagnosed as having EEC and underwent hysterectomy. Only
      patients who underwent preoperative PET/CT imaging were included in the study.
      The thickness and volume of the uterine lesion, and its maximum standardized
      uptake value as obtained using PET/CT and hysterectomy pathology specimens were
      recorded. Results: Tumor size (p=0.051) and volume (p=0.404) were not found to be
      correlated with the imaging method used in premenopausal women and pathologic
      specimens. However, there was a correlation in postmenopausal women (p<0.001 for
      tumor size and p<0.001 for tumor volume). PET/CT has higher sensitivity,
      specificity, and positive predictive value in the postmenopausal period in the
      detection of >20 mm uterine tumors. Conclusion: PET/CT has a limited role in the
      measurement of the size of uterine lesions in all patients, especially in the
      premenopausal period; therefore, we recommend that frozen-section examinations be
      used intraoperatively to decide on lymph node dissection.

PMID- 29662717
TI  - Tumor necrosis factor alfa and interleukin 1 alfa induced phosphorylation and
      degradation of inhibitory kappa B alpha are regulated by estradiol in endometrial
      cells.
AB  - Objective: When bound to the inhibitory kappa B (IkB) protein, the transcription
      factor nuclear factor kappa B (NF-kB) remains inactively in the cytoplasm.
      Activated NF-kB upregulates the gene expression of many chemokines including
      monocyte chemoattractant protein-1 and interleukin (IL)-8. We hypothesized that
      estrogen may regulate IkB phosphorylation and degradation thus influencing NF-kB
      dependent gene expression. Regulation of chemokines by estrogen is different in
      uterine endometrial cells when compared to ectopic endometrial cells of
      endometriosis. Materials and Methods: We investigated the in vivo expression of
      IkB in normal endometrium and in eutopic and ectopic endometrium of women with
      endometriosis. We then studied in cultured endometrial cells to assess the
      effects of estradiol on IkB and NF-kB function. Results: Normal endometrium from
      mid-late proliferative phase revealed the strongest IkB immunoreactivity
      throughout the cycle (p<0.05). When compared to paired homologous eutopic
      endometrium, ectopic endometrium revealed significantly less immunoreactivity for
      IkB (p<0.05). Moreover, estradiol induced a decrease in tumor necrosis factor-and
      IL-1-induced IkB phosphorylation, and also decreased the levels of active-NF-kB
      (p<0.05). Conclusion: Our results support the conclusion that one pathway for
      estradiol-mediated NF-kB inhibition occurs through the down-regulation of IkB
      phosphorylation. We propose that the estradiol-induced regulation of IkB and
      consequent reduction in active-NF-kB may affect inflammatory responses in human
      endometrial cells.

PMID- 29662719
TI  - The importance of uterosacral ligament anatomy in overactive bladder: A
      preliminary study.
AB  - Objective: To evaluate whether uterosacral ligament (USL) thickness measured
      using magnetic resonance imaging (MRI) was associated with overactive bladder
      (OAB) in otherwise healthy women. Materials and Methods: The study comprised 27
      women with OAB and 27 healthy women (control group) who were followed up at the
      Obstetrics and Gynecology Department of a tertiary referral center. All subjects
      were evaluated using pelvic MRI to determine the transverse USL thickness. These
      measurements were compared between the two groups. p values less than 0.05 were
      considered statistically significant. Results: The mean age of women in the OAB
      and control groups were 43.88+/-9.36 years and 39.92+/-5.36 years, respectively.
      The mean body mass index in the OAB group was 29.77+/-4.82 kg/m2 and 27.49+/-3.44
      kg/m2 in the control group. In the comparison of Pelvic Organ Prolapse
      Quantification system stages between the groups, no statistically significant
      relationship was determined. In the OAB group, the mean right USL thickness was
      2.04+/-0.34 mm, and the mean left USL was 2.04+/-0.52 mm. In the control group,
      the mean right USL thickness was 2.17+/-0.47 mm, and the mean left USL was 2.09+/
      0.51 mm. There were no statistically significant differences in terms of USL
      thickness between the OAB and control groups (p>0.05). Conclusion: No previous
      studies have been identified in the literature that have investigated the
      relationship between USL thicknesses and urinary incontinence. In the present
      study, no significant relationship could be demonstrated between right and left
      USL thicknesses of the OAB and control groups. This was a preliminary study, and
      further research with larger sample sizes is required to reach a final
      conclusion.

PMID- 29662720
TI  - Role of Active Versus Passive Complementary and Integrative Health Approaches in
      Pain Management.
AB  - Background: A general conclusion about the treatment of chronic, noncancer pain
      is that the results from traditional, passive modalities are disheartening.
      Perhaps this may be due to the propensity of patients to seek out passive versus
      active treatments. In pain management, active treatments should be the primary
      focus, with passive interventions as an adjunct. Objective: The current study
      tested the hypotheses that Veterans would report a greater significant increase
      in active versus transitional and active versus passive complementary and
      integrative health (CIH) utilization after completing a formal pain education
      program. Methods: The current study is a secondary analysis of existing data from
      an original study. The current study used a quasi-experimental, 1-group, pre
      /posttest design. One hundred three Veterans completed a 12-week, "Pain Education
      School" program at a Midwestern VA Medical Center between November 4, 2011, and
      October 26, 2012. As part of the introduction and conclusion of the program, all
      Veterans completed a pre- and posteducation assessment which included an
      adaptation of the Complementary and Alternative Medicine Questionnaire(c),
      SECTION A: Use of Alternative Health Care Providers measure. Results: Significant
      differences were found between the pre- and posttest measures of use of active (P
      = .000) (p<.001), transitional (P = .011), and passive (P = .007) CIH modalities.
      Conclusion: The current findings suggest that an educational intervention in
      conjunction with the availability of treatment options has the potential to
      increase the use of those treatments. The current pain education program also
      seems to be aligned with the goal of pain self-management, which is to utilize
      more active interventions as a primary therapy.

PMID- 29662721
TI  - Neural Mechanisms of Qigong Sensory Training Massage for Children With Autism
      Spectrum Disorder: A Feasibility Study.
AB  - Objectives: Despite the enormous prevalence of autism spectrum disorder (ASD),
      its global impact has yet to be realized. Millions of families worldwide need
      effective treatments to help them get through everyday challenges like eating,
      sleeping, digestion, and social interaction. Qigong Sensory Training (QST) is a
      nonverbal, parent-delivered intervention recently shown to be effective at
      reducing these everyday challenges in children with ASD. This study tested the
      feasibility of a protocol for investigating QST's neural mechanism. Methods:
      During a single visit, 20 children, 4- to 7-year-old, with ASD viewed images of
      emotional faces before and after receiving QST or watching a video (controls).
      Heart rate variability was recorded throughout the visit, and power in the high
      frequency band (0.15-0.4 Hz) was calculated to estimate parasympathetic tone in 5
      s nonoverlapping windows. Cerebral oximetry of prefrontal cortex was recorded
      during rest and while viewing emotional faces. Results: 95% completion rate and
      7.6% missing data met a priori standards confirming protocol feasibility for
      future studies. Preliminary data suggest: (1) during the intervention,
      parasympathetic tone increased more in children receiving massage (M = 2.9, SD =
      0.3) versus controls (M = 2.5, SD = 0.5); (2) while viewing emotional faces post
      intervention, parasympathetic tone was more affected (reduced) in the massage
      group (p = 0.036); and (3) prefrontal cortex response to emotional faces was
      greater after massage compared to controls. These results did not reach
      statistical significance in this small study powered to test feasibility.
      Discussion/Conclusion: This study demonstrates solid protocol feasibility. If
      replicated in a larger sample, these findings would provide important clues to
      the neural mechanism of action underlying QST's efficacy for improving sensory,
      social, and communication difficulties in children with autism.

PMID- 29662723
TI  - HIV and Chronic Pain, Part 2: Addressing the Opioid Public Health Crisis.

PMID- 29662722
TI  - Acupuncture for Chronic Pain in the Vermont Medicaid Population: A Prospective,
      Pragmatic Intervention Trial.
AB  - Introduction: In response to the opioid crisis, the 2016 Vermont legislature
      commissioned a study to assess acupuncture for patients with chronic pain in the
      Vermont Medicaid population. Objective: To assess the feasibility, acceptability,
      and effectiveness of acupuncture provided by licensed acupuncturists for Vermont
      Medicaid patients with chronic pain. Methods: A total of 156 Medicaid patients
      with chronic pain were offered up to 12 acupuncture treatments within a 60-day
      period at the offices of 28 Vermont licensed acupuncturists. PROMIS(r)
      questionnaires were administered prior to and at the end of the treatment period
      to assess changes in pain intensity, pain interference, physical function,
      fatigue, anxiety, depression, sleep disturbance, and social isolation.
      Questionnaires also captured patients' overall impressions of treatments as well
      as self-reported changes in medication use and work function. Results: One
      hundred eleven women (71%) and 45 men (29%) with a wide range of pain complaints
      received a mean of 8.2 treatments during the intervention period. Measurements
      captured prior to and at the end of the treatment period showed significant
      improvements in group mean pain intensity, pain interference, physical function,
      fatigue, anxiety, depression, sleep disturbance, and social isolation as assessed
      by Patient-Reported Outcomes Measurement Information System (PROMIS) measures
      (paired t tests, P < .01). Fifty-seven percent of patients using analgesic
      (nonopioid) medication reported reductions in use. Thirty-two percent of patients
      using opioid medication reported reductions in use of opioid medication following
      the intervention. Seventy-four percent of employed patients reported improved
      capacity to work. Ninety-six percent of patients said that they would recommend
      acupuncture to others with chronic pain, and 91% reported qualitative
      improvements, including physical (31%), functional/behavioral (29%), and psycho
      emotional (24%) improvements. Conclusions: Our findings demonstrate that
      acupuncture treatment for chronic pain is feasible and well received by patients
      in the Vermont Medicaid population. Receiving care from Licensed Acupuncturists
      was associated with significant improvements in physical, functional, psycho
      emotional, and occupational outcomes compared with before receiving acupuncture
      treatments.

PMID- 29662724
TI  - Frequency and Determinants of Inappropriate Use of Treadmill Stress Test for
      Coronary Artery Disease.
AB  - Background In developing countries like Pakistan, treatment is mediated by
      private and public healthcare setups with a limited budget for health facilities.
      Moreover, the inappropriate use of treadmill tests imposes a burden on healthcare
      resources and leads to unwarranted interventions. Our aim is to assess the
      prevalence and predictors of inappropriate referrals for the exercise tolerance
      test (ETT) to diagnose coronary artery disease (CAD) while taking public and
      private healthcare settings into consideration. Methods A cross-sectional study
      was conducted to find the prevalence of the inappropriate use of ETT to diagnose
      obstructive CAD and to determine the factors responsible for it. A total of 264
      patients were enrolled from outpatient departments in Karachi. The inclusion
      criterion was the referral of treadmill testing for the diagnosis of CAT. The
      analysis was performed by logistic regression models to ascertain independent
      predictors of inappropriate use. Results Exercise stress tests were found to be
      inappropriate in 209 (79%) patients. The study indicated that the majority of
      patients had a low or very low pre-test probability of CAD. Diabetes,
      hypertension, and dyslipidemia were less frequent in the inappropriate as
      compared to the appropriate referrals (10%, 45%, and 16% versus 20%, 69%, and
      32%). Both public and private sectors showed a high prevalence of inappropriate
      testing, but it was much higher in the latter (27% versus 73%, P < 0.001). In all
      regression models, the private healthcare system was the major independent
      predictor for inappropriate indications of ETT with an average odds ratio of 4.9
      (P < 0.001). Conclusion The high prevalence of ETT referrals was found for the
      diagnosis of CAD. This result was consistent with both public and private
      healthcare systems, but it was considerably higher in private setups.
      Comorbidities, number of risk factors, and cardiovascular risk were not
      associated with the inappropriate use of ETT.

PMID- 29662725
TI  - Multiple Cranial Neuropathies in a Patient with Diffuse Large B-cell Lymphoma:
      Case Report and Review of Literature.
AB  - Neuropathies can occur in patients with diffuse large B-cell lymphoma (DLBCL) at
      any stage of the disease as a presenting symptom or during later stages of
      illness. A wide spectrum of neurological association is known to occur with
      DLBCL, ranging from cranial nerve palsies to peripheral neuropathies. Evaluation
      of cranial and peripheral neuropathies in patients with DLBCL requires meticulous
      clinical, imaging, and electrodiagnostic testing. A 75-year-old right-handed
      female with a known history of multiple cranial neuropathies and DLBCL presented
      with acute dysphagia and upper extremity weakness of one-week duration. On
      evaluation, she was found to have right vagal nerve palsy. Cerebrospinal fluid
      (CSF) analysis along with flow cytometry testing showed CD19 and CD20 positive B
      cells, confirming neoplastic infiltration of CSF. We describe the case and review
      the literature of the association of cranial nerve palsies with DLBCL.

PMID- 29662726
TI  - Chronic Debilitating Headache in Adults Caused by Craniocerebral Disproportion:
      Treatment by Cranial Vault Expansion.
AB  - Craniocerebral disproportion is rarely considered as a cause for chronic,
      debilitating headache in adults. Children reported with this disorder typically
      suffer from headaches and lethargy for many years and have multisutural
      synostosis. The terms craniocerebral disproportion, craniostenosis, and slit
      ventricle syndrome are used inconsistently as diagnostic designations. Three
      adults with craniocerebral disproportion who had been treated in infancy for two
      different pathologies are reported. All benefited greatly from cranial vault
      expansion.

PMID- 29662727
TI  - Paratesticular Serous Papillary Carcinoma of High Grade and Malignant Potential:
      A Rare Case with a Role for Adjuvant Therapy.
AB  - Paratesticular serous papillary carcinomas are very rare, with less than 40 cases
      reported in the literature. These neoplasms are Mullerian in origin, and more
      commonly seen as epithelial-type ovarian cancer. Given the rarity of this tumor
      in men, staging and recommended treatment options do not exist. Herein, we
      present the case of a 35-year-old male with high-grade invasive serous papillary
      carcinoma. He was diagnosed after left radical orchiectomy for paratesticular
      mass and subsequently treated with adjuvant chemotherapy according to existing
      recommendations for its ovarian counterpart. Chemotherapy was well tolerated and
      surveillance imaging has shown no evidence of disease. This case suggests a
      potential role for adjuvant therapy in patients with high-grade paratesticular
      serous papillary carcinoma.

PMID- 29662728
TI  - Breastfeeding and Weaning: Practices in Urban Slums of Southern Punjab, Pakistan.
AB  - Objective Proper breastfeeding and weaning practices are effective ways of
      reducing childhood morbidity and mortality. This study aimed to find out
      breastfeeding and weaning practices among infants of six months to one year in
      urban slums of Bahawalpur city. By evaluating the knowledge and attitude of
      lactating mothers regarding their child feeding habits, modifications and
      specific interventions can be implemented to improve the breastfeeding and
      weaning practices of the area. Methods A cross-sectional descriptive study was
      carried out in the Shahdrah slums of Bahawalpur City after getting approval from
      the institutional review board of Quaid-e-Azam Medical College, Bahawalpur. The
      survey was conducted from April 10, 2017 to May 30, 2017. One hundred mothers of
      infants aging six months to one year of age were interviewed. Mothers filled a
      customized questionnaire, consisting of questions about logistic variables,
      breastfeeding, and weaning. Statistical analysis was performed using Statistical
      Package for the Social Sciences (SPSS) version 22.0 (IBM Corp. Armonk, NY, USA).
      Results The mean age of the women was 24+2 years. It was found that 74% (n=74) of
      the mothers had one to three children, 85% (n=85) of the mothers were
      breastfeeding their infants at the time of the study, 40% (n=40) of the mothers
      were illiterate, 16% (n=16) of the mothers had secondary education, and 87%
      (n=87) of the mothers were nonworking women. Out of 85 women who were
      breastfeeding, 95% (n=80) of the women were 18-23 years of age. We found that 57%
      (n=57) of the infants were six to nine months old and the remaining 43% (n=43)
      were up to 12 months of age. Regarding the initiation of breastfeeding, 60% of
      the females started soon after delivery, and 32% started within two to seven
      days. We found that 70% (9/13) of the working women and 87.4% (76/87) of the non
      working women were breastfeeding. The study found that 92.3% (12/13) of the
      working women and 88.5% (77/87) of the non-working women were weaning. Conclusion
      A majority of the mothers were breastfeeding and weaning their babies. The
      factors documented were young age, low parity, no working status, and nuclear
      families. The commonly used feeding materials were cereals, banana, rice, and
      bread. No side effects of weaning were observed. Weaning was associated by late
      age, parity, non-working status, educational status of father, and nuclear
      families.

PMID- 29662729
TI  - The Clinical Evaluation of Alcohol Intoxication Is Inaccurate in Trauma Patients.
AB  - BACKGROUND: Discharging patients from emergency centers based on the clinical
      features of intoxication alone may be dangerous, as these may poorly correlate
      with ethanol measurements. OBJECTIVE: We determined the feasibility of utilizing
      a hand-held breath alcohol analyzer to aid in the disposition of intoxicated
      trauma patients by comparing serial breathalyzer (Intoximeter, Alco-Sensor FST,
      St. Louis, Missouri, USA] data with clinical assessments in determining the
      readiness of trauma patients for discharge. METHODS: A total of 20 legally
      intoxicated (LI) patients (blood alcohol concentration (BAC) >80 mg/dL) brought
      to our trauma center were prospectively investigated. Serial breath samples were
      obtained using a breathalyzer as a surrogate measure of repeated BAC. A clinical
      exam (nystagmus, one-leg balance, heel-toe walk) was performed prior to each
      breath sampling. RESULTS: The enrollees were 85% male, age 30+/-10 (range 19-51),
      with a body mass index (BMI) of 29+/-7. The average initial body alcohol level
      (BAL) was 245+/-61 (range 162-370) mg/dL. Based on breath samples, the alcohol
      elimination rates varied from 21.5 mg/dL/hr to 45.7 mg/dL/hr (mean 28.5
      mg/dL/hr). There were no significant differences in alcohol elimination rates by
      gender, age, or BMI. The clinical exam also varied widely among patients; only
      seven of 16 (44%) LI patients demonstrated horizontal nystagmus (suggesting
      sobriety when actually LI) and the majority of the LI patients (66%) were able to
      complete the balance tasks (suggesting sobriety). CONCLUSION: Intoxicated trauma
      patients have an unreliable clinical sobriety exam and a wide range of alcohol
      elimination rates. The portable alcohol breath analyzer represents a potential
      option to easily and inexpensively establish legal sobriety in this population.

PMID- 29662730
TI  - Myelopathy Improvement Following Removal of Cervical Sublaminar Wiring.
AB  - Posterior cervical wiring has been used by spine surgeons in fixation procedures
      for patients with spinal instability. It is historically considered an effective
      method of treating cervical instability with a low risk of complications leading
      to neurological deterioration. We experienced a case of delayed neurological
      decline associated with myelopathy, lower extremity spasticity, and associated
      syringomyelia secondary to instrumentation failure and resultant sublaminar wire
      protrusion into the cervical spinal cord. In the present case, the construct was
      removed and the patient underwent a durotomy repair and a posterior fusion of
      cervical levels 1 and 2 via screw placement under image guidance with a
      subsequent functional improvement back to baseline. We report this case and
      review the literature on the complications associated with cervical wire fusion
      and the methods of minimizing these risks.

PMID- 29662731
TI  - Intraventricular Haemorrhage Complicated by Hydrocephalus in an Acutely
      Encephalopathic Preterm Infant.
AB  - Intraventricular haemorrhage (IVH) is characterized by bleeding of the immature
      subependymal germinal matrix in preterm infants, but the pathogenesis is
      multifactorial. IVH and posthaemorrhagic hydrocephalus (PHH) are common causes of
      neonatal morbidity and mortality among preterm infants. We describe a preterm
      male infant who was born clinically stillbirth; became moderately severe
      encephalopathic. He had bilateral IVH (III right and IV left) with consequent
      PHH. His incredible outcome following a stormy perinatal period appears
      intriguing. Long-term follow-up is needed to evaluate the severity of deficits as
      he matures. Whether therapeutic cooling would have made a difference or not is
      debatable.

PMID- 29662732
TI  - Institutional Review of Hemorrhagic Pelvic Emergencies Effectively Managed with
      Percutaneous Arterial Embolization.
AB  - OBJECTIVE: Our aim was to review the results of pelvic arterial embolization
      (PAE) performed in the interventional radiology suite. METHOD: The data of all
      patients in whom pelvic angioembolization was performed was collected from July
      2011 to June 2017. Procedures were performed by an experienced interventional
      radiologist. The clinical and laboratory data, as well as the outcome data, were
      obtained from the medical records of our hospital. The following parameters were
      collected for each patient, including the age, gender, presenting symptoms, site
      of bleeding, catheters used for embolization, material used for embolization,
      previous computed tomography (CT) scan and/or focused assessment with sonography
      for trauma (FAST) ultrasound, average hemoglobin before the procedure, and
      patient clinical status on discharge. RESULT: A total of 37 patients underwent
      pelvic angiography for acute hemorrhage at our institution. They had contrast
      blush, active extravasation, or abnormal vascularity from the branches of the
      internal iliac artery and underwent therapeutic transcatheter embolization. A
      total of 29 patients (78.3%) were male and 8 (21.7%) were female. The average age
      was 30.0 years (range: 6-90 year). Of these, 16 patients (43.2%) presented with
      road traffic accidents (RTAs), six with gunshot injuries (16.2%), six with
      iatrogenic injuries (16.2%), four with a history of a fall (10.8%), two with bomb
      blast injuries (5.4%), one with a history of a glass injury (2.7%), one had a
      history of a roof falling on her during an earthquake, and one patient had a
      pelvic pseudoaneurysm secondary to an abscess. The type of embolic material used
      for embolization included coils in 16 patients, polyvinyl alcohol (PVA) particles
      were used in eight patients, both PVA particles and coils were used in 11
      patients, and glue was used in one patient. All were successfully embolized.
      Thirty-four were discharged while three patients expired during the course of
      hospital stay due to other coexisting morbidities. CONCLUSION: The management of
      pelvic injuries has always been a topic of debate, with multiple methods reported
      to date but growing evidence supports the use of pelvic arterial embolization in
      hemorrhagic pelvic injuries. The formulation of a standardized protocol is the
      need of the day.

PMID- 29662733
TI  - Psoriasis and Cardiovascular Diseases: A Literature Review to Determine the
      Causal Relationship.
AB  - Psoriasis is a chronic, complex autoimmune disease characterized by erythematous,
      scaly patches over extensor aspects of skin and is associated with joint
      involvement in about one-third of patients. An association between psoriasis and
      cardiovascular diseases (CVD) has been a topic of dilemma, and many studies have
      shown an increased risk of cardiovascular morbidity in patients with psoriasis.
      There is increasing evidence that psoriasis is associated with higher risk of CVD
      and increased prevalence of cardiovascular risk factors, as compared with the
      general population. We provide an extensive review of the literature and adhere
      to Gordis guidelines to show a positive association between psoriasis and
      cardiovascular events.

PMID- 29662734
TI  - Effect of a water extract of Curcuma longa on emotional states in healthy
      participants.
AB  - Physiological symptoms of mood disturbances, such as fatigue or anxiety, are
      closely related to inflammation in the central nervous system or the whole body.
      Curcuma longa is widely used as a dietary spice and has been reported to have
      anti-inflammatory activity. To investigate the effect of a water extract of C.
      longa (WEC) on emotional states, a randomized, double-blind, placebo-controlled,
      parallel-group study was conducted with healthy participants. Forty-eight
      participants were randomly assigned to receive five tablets containing 150 mg WEC
      and 0.40 mg bisacurone (L-WEC group), five tablets containing 900 mg WEC and 2.40
      mg bisacurone (H-WEC group), or matching placebo tablets (placebo group) daily
      for 8 weeks. Participant emotional states were measured every 4 weeks using the
      Profile of Mood States (POMS). The changes from week 0 to week 8 in the fatigue
      score of the POMS were significantly lower in the L-WEC group than in the placebo
      group. This result suggests that daily intake of 150 mg WEC may positively
      influence emotional fatigue, and further investigation focused on emotional
      fatigue is needed.

PMID- 29662735
TI  - Effect of superoxide dismutase and manganese on superoxide tolerance in
      Lactobacillus casei strain Shirota and analysis of multiple manganese
      transporters.
AB  - The Lactobacillus casei/paracasei group accumulates a high level of manganese,
      which works to scavenge superoxide anions produced during aerobic growth. The
      genome of L. casei strain Shirota, however, also codes the gene for superoxide
      dismutase (SOD), sodA, which catalyzes the dismutation of superoxide anion into
      hydrogen peroxide and oxygen. We anticipated that the SOD and/or manganese may
      contribute to the aerobic growth of L. casei Shirota and tried to clarify how L.
      casei Shirota can eliminate the toxicity of superoxide anion. When the sodA of L.
      casei Shirota was cloned and expressed in Escherichia coli as well as in L. casei
      Shirota, there was no increase in SOD activity detected, meaning that the protein
      is in an inactive form, even if it is produced in L. casei Shirota. We next
      focused on the role of the manganese transport system of L. casei Shirota. One
      ABC-type manganese transporter (mtsCBA cluster) and three NRAMP-type manganese
      transporters (mntH1, mntH2, and mntH3) are coded in the genome. To clarify the
      role of these genes, we disrupted one or more of these manganese transporter
      genes in different combinations and analyzed the intracellular manganese levels.
      As a result, we found that NRAMP-type manganese transporters coded by mntH1 and
      mntH2 and ABC-type manganese transporter coded by mtsCBA cluster are
      complementarily involved in the accumulation of intracellular manganese and are
      necessary for aerobic growth of L. casei Shirota. These results indicate that
      intracellular manganese accumulated by multiple complementary manganese
      transporters, but not SOD, plays a pivotal role in tolerance to superoxide in L.
      casei Shirota.

PMID- 29662736
TI  - Investigating the transmissibility of tet(W) in bifidobacteria exposed to acid
      and bile stress.
AB  - Transfer of antibiotic resistance genes from probiotic bacteria to pathogens
      poses a safety concern. Orally administered probiotics are exposed to stressful
      conditions during gastrointestinal transit. In this study, filter mating
      experiments were performed to investigate the potential role of exposure of
      Bifidobacterium isolates to acid and bile stress on the transfer of a
      tetracycline resistance gene, tet(W), to Enterococcus faecalis ATCC 51299. No E.
      faecalis transconjugants were obtained after mating with either stressed or
      unstressed Bifidobacterium, thereby suggesting that tet(W) could not be
      transferred as a result of exposure to gastrointestinal stresses.

PMID- 29662737
TI  - 4G-beta-D-galactosylsucrose as a prebiotics may improve underweight in inpatients
      with schizophrenia.
AB  - Japanese inpatients with schizophrenia have a higher mortality risk due to
      underweight compared with the general population. The aim of this study was to
      investigate the effect of 4G-beta-D-galactosylsucrose on body weight in
      underweight schizophrenia inpatients. The study population consisted of 5 male
      and 11 female subjects aged 63.0 +/- 10.9 years. The subjects had ingested 3.0
      g/day 4G-beta-D-galactosylsucrose for 6 months. BMI increased significantly, from
      20.9 +/- 3.7 kg/m2 to 22.3 +/- 4.3 kg/m2, and this was accompanied by a
      significant increase in Bifidobacterium in the fecal microbiota, which increased
      from 16.1 +/- 12.6% to 21.5 +/- 13.9%. Although 4G-beta-D-galactosylsucrose
      appears to have no significant effects on nutritional indicators such as serum
      albumin, it may alleviate underweight in inpatients with schizophrenia. Body
      weight may be related to fecal microbiota composition.

PMID- 29662738
TI  - Editorial.

PMID- 29662739
TI  - Decompression in Adult Lumbar Deformity Surgery Is Associated With Increased
      Perioperative Complications but Favorable Long-Term Outcomes.
AB  - Study Design: Retrospective cohort study. Objectives: To analyze the impact of
      performing a formal decompression in patients with adult lumbar scoliosis with
      symptomatic spinal stenosis on perioperative complications and long-term
      outcomes. Methods: Adult patients undergoing at least 5 levels of fusion to the
      sacrum with iliac fixation from 2002 to 2008 who had a minimum 5-year follow-up
      at one institution were studied. Patients who had 3-column osteotomy were
      excluded from the study. Perioperative complications and clinical outcomes
      (Scoliosis Research Society [SRS], Oswestry Disability Index [ODI], and Numerical
      Rating Scale [NRS] back/leg pain) were analyzed. Patients who underwent formal
      laminectomy/decompressions were compared with those who did not. Differences
      between the 2 groups were analyzed using Student's t test. Results: A total of
      147 patients were included in the study (Decompression: n = 55 [37%], No
      decompression: n = 92 [63%]). Average fusion levels for the decompression and no
      decompression groups were 11 and 12 levels, respectively (P = .26). Mean
      improvements in SRS domains for decompression versus no decompression patients,
      respectively, were pain (1.1 vs 0.9, P = .3), function (0.7 vs 0.5, P = .09),
      self-image (1.1 vs 1.1, P = .9), and mental health (0.5 vs 0.4, P = .5).
      Furthermore, additional mean improvements were ODI (21 vs 21, P = .14), NRS-Back
      pain (3.0 vs 1.3, P = .16), and NRS-Leg pain (3.9 vs 0.5, P = .002). Complication
      rates between the decompression group and no decompression group differed in
      incidental durotomies (18.2% vs 0%) and cardiac-related (9.1% vs 1.1%).
      Conclusions: Performing a formal decompression in adult lumbar scoliosis with
      symptomatic spinal stenosis is associated with increased perioperative
      complications but favorable long-term clinical outcomes.

PMID- 29662740
TI  - Low-Density Pedicle Screw Constructs for Adolescent Idiopathic Scoliosis:
      Evaluation of Effectiveness and Cost.
AB  - Study Design: Retrospective cohort study. Objective: To determine whether a low
      density (LD) screw construct can achieve curve correction similar to a high
      density (HD) construct in adolescent scoliosis. Methods: Patients treated
      operatively for idiopathic scoliosis between 2007 and 2011 were identified
      through a database review. A consistent LD screw construct was used. Radiographic
      assessment included percent correction of major and fractional lumbar curves, T5
      T12 kyphosis, and angle of lowest instrumented vertebra (LIV). Costs were
      compared with HD constructs. Results: Thirty-five patients were included in the
      analysis. Ages ranged from 12 to 19 years (mean = 14.9 years). Average screw
      density was 1.2 screws per level (range = 1.07-1.5 screws). Mean percent curve
      correction at latest follow-up: major curve, 66.9%; fractional lumbar curve, 63%.
      Average postoperative thoracic kyphosis: 29.5 degrees . Mean LIV angle: 5.6
      degrees . Average construct cost was $14 871 per case compared with $23 840 per
      case if all levels had been instrumented with 2 screws, amounting to an average
      savings of $9000. Conclusions: Our LD screw construct is among the lowest density
      constructs reported and achieves curve correction comparable to HD constructs at
      substantially lower cost.

PMID- 29662741
TI  - Predictive Factors for the Outcome of Surgical Treatment of Lumbar Spondylolysis
      in Young Sporting Individuals.
AB  - Study Design: Retrospective consecutive case series. Objectives: Only few
      sporting individuals with symptomatic lumbar pars injuries require surgical
      repair and it is often difficult to predict the outcome following surgery. The
      factors that predict the outcome after direct repair of lumbar pars defect was
      evaluated clinically and statistically. The preoperative background variables
      both subjective and objective as well as radiological evaluation were used in a
      multiple regression model to find the strong predictors of postoperative outcome
      as measured by VAS (visual analogue scores), ODI (Oswestry Disability Index) and
      SF-36 (Short Form). Methods: Fifty-two consecutive young sporting individuals
      with a mean age of 19 years (range 8-30 years) were treated surgically for lumbar
      pars defect confirmed on imaging studies (ie, single-photon emission computed
      tomography, computed tomography, and magnetic resonance imaging). Fifty patients
      completed the VAS, ODI, and SF-36 questionnaires as a part of their assessment.
      Preoperative background variables were used in a multiple regression model to
      find the strongest predictor of postoperative outcome as measured by ODI. Ethical
      approval was taken by the institutional review board. Results: Buck's screw
      repair of the pars defect was carried out in 44 patients (33 males, 11 female):
      unilateral in 8 patients (7 males, 1 female) and bilateral in 36 patients (26
      males, 10 females). Although age at surgery showed linear colinearity (rho =
      0.32, P < .05), it was not significant in the model. The most consistent
      association with the preoperative VAS score were the pre- and postoperative ODI
      scores, that is, rho = 0.51 (P < .01) and rho = 0.33 (P < .05), respectively. In
      the bilateral group, with Buck's repair at a single level, that is, 33 of 36
      (93%) patients had returned to sports at a mean time of 7.5 months (range 6-12
      months). Overall, 44 of 52 (84%) individuals had returned to their sports with
      posttreatment ODI score of <10. The stepwise regression modeling suggested 6
      independent factors (preoperative ODI, preoperative SF-36 physical component
      summary (PCS), Buck's repair, multiple operations, professionalism, and pars
      defect at L3), as the determinants of the outcome (ie, postoperative ODI) in
      80.9% patients (R2 = 0.809). Conclusions: The outcome after direct repair of pars
      defect in those younger than 25 years runs a predictable course. Professionalism
      in sports has a high impact on the outcome. Preoperative ODI and SF-36 PCS scores
      are significant predictors of good functional outcome. The regression equation
      can predict the outcome in 80.9% sporting individuals undergoing Buck's repair.

PMID- 29662742
TI  - Total Disc Replacement Versus Anterior-Posterior Interbody Fusion in the Lumbar
      Spine and Lumbosacral Junction: A Cost Analysis.
AB  - Study Design: Prospective observational cohort study. Objectives: To analyze
      clinical and economic results in patients with degenerative disc disease in the
      lumbar area for patients who received combined anterior and posterior fusion or
      total disc replacement (TDR). Methods: The study included 75 patients, 38 in the
      fusion group and 37 in the TDR group, who received either anterior/posterior
      fusion or TDR for lumbar disc disease from January 2005 to December 2008 with a
      minimum follow-up of 24 months. We collected data with regard to clinical
      parameters, demographics, visual analogue scale scores, Oswestry Disability Index
      scores, SF-36 and SF-6D data, surgery time, amount of blood loss, transfusion of
      blood products, number of levels, duration of hospital stay, and complications.
      For cost analysis, general infrastructure, theatre costs, as well as implant
      costs were examined, leading to primary hospital costs. Furthermore, average
      revision costs were examined, based on the actual data. Statistical analysis was
      performed using t tests for normal contribution and Mann-Whitney test for skew
      distributed values. The significance level was set to .05. Results: There was a
      higher surgery time, more blood loss, and longer hospital stay for the fusion
      group, compared with the TDR group. In addition, the hospital costs for the
      primary procedure and revision were 35% higher in the fusion group. The clinical
      data in terms of SF-36 and SF-6D showed no difference between these 2 groups.
      Conclusions: TDR is a good alternative to anterior and posterior lumbar fusion in
      terms of short follow-up analysis for clinical data and cost analysis. General
      advice cannot be given due to missing data for long-term costs in terms of
      surgical treatment of adjacent level or further fusion techniques.

PMID- 29662743
TI  - Trends Analysis of rhBMP2 Utilization in Single-Level Anterior Lumbar Interbody
      Fusion in the United States.
AB  - Study Design: Retrospective case study. Objective: To evaluate the trends and
      demographics of recombinant human bone morphogenetic protein 2 (rhBMP2)
      utilization in single-level anterior lumbar interbody fusion (ALIF) in the United
      States. Methods: Patients who underwent single-level ALIF from 2005 to 2011 were
      identified by searching ICD-9 diagnosis and procedure codes in the PearlDiver
      Patient Records Database (PearlDiver Technologies, Fort Wayne, IN), a national
      database of orthopedic insurance records. The year of procedure, age, gender, and
      region of the United States were analyzed for each patient. Results: A total of
      921 patients were identified who underwent a single-level ALIF in this study. The
      average rate of single-level ALIF with rhBMP2 utilization increased (35%-48%)
      from 2005 to 2009, but sharply decreased to 16.7% in 2010 and 15.0% in 2011. The
      overall incidence of single-level ALIF without rhBMP2 (0.20 cases per 100 000
      patients) was more than twice of the incidence of single-level ALIF with rhBMP2
      (0.09 cases per 100 000 patients). The average rate of single-level ALIF with
      rhBMP2 utilization is highest in West (41.4%), followed by Midwest (33.3%), South
      (26.5%) and Northeast (22.2%). The highest incidence of single-level ALIF with
      rhBMP2 was observed in the group aged less than 65 years (compared with any other
      age groups, P < .001), with an incidence of 0.21 per 100 000 patients.
      Conclusions: The incidence of rhBMP2 utilization in single-level ALIF increased
      from 2006 to 2009, but decreased in 2010 and 2011. The Northeast region had the
      lowest incidence of rhBMP2 utilization. The group aged less than 65 years trended
      to have the higher incidence of single-level ALIF with rhBMP2 utilization.

PMID- 29662744
TI  - Postoperative Complications Associated With rhBMP2 Use in
      Posterior/Posterolateral Lumbar Fusion.
AB  - Study Design: Retrospective database review. Objective: Posterior/posterolateral
      lumbar fusion (PLF) is an effective treatment for a variety of spinal disorders;
      however, variations in surgical technique have different complication profiles.
      The aim of our study was to quantify the frequency of various complications in
      patients undergoing PLF with and without human recombinant bone morphogenetic
      protein 2 (rhBMP2). Methods: We queried the orthopedic subset of the Medicare
      database (PearlDiver) between 2005 and 2011 for patients undergoing PLF
      procedures with and without rhBMP2. Complication and reoperation rates were
      analyzed within 1 year of the index procedure. Complications assessed include:
      acute renal failure, deep vein thrombosis, dural tear, hematoma, heterotopic
      ossification, incision and drainage, cardiac complications, nervous system
      complications, osteolysis, pneumonia, pseudarthrosis, pulmonary embolism,
      radiculopathy, respiratory complications, sepsis, urinary retention, urinary
      tract infection, mechanical, and wound complications. Chi-square analysis was
      used to calculate the complication differences between the groups. Results: Our
      data revealed higher overall complication rates in patients undergoing PLF with
      rhBMP2 versus no_rhBMP2 (76.9% vs 68.8%, P < .05). Stratified by gender, rhBMP2
      males had higher rates of mechanical complications, pseudarthrosis, and
      reoperations compared with no_rhBMP2 males (P < .05), whereas rhBMP2 females had
      higher rates of pseudarthrosis, urinary tract infection, and urinary retention
      compared with no_rhBMP2 females (P < .05). Conclusion: Our data revealed higher
      overall complication rates in PLF patients given rhBMP2 compared with no_rhBMP2.
      Furthermore, our data suggests that rhBMP2-associated complications may be gender
      specific.

PMID- 29662745
TI  - Negative Sagittal Balance Following Adult Spinal Deformity Surgery.
AB  - Study Design: Retrospective cohort study. Objective: Elucidate negative sagittal
      balance following adult spinal deformity surgery. Methods: We conducted a
      retrospective review of adult spinal deformity patients who underwent long fusion
      (>5 levels) to the sacrum by a single surgeon at a single institution between
      2011 and 2015. Patients were divided into cohorts of postoperative sagittal
      vertical axis (SVA) <-10 mm, between -10 and +10 mm, or >+10 mm, denoted as
      groups 1, 2, and 3, respectively. Univariate analysis compared preoperative
      factors between the groups, and a multivariable logistic regression model was
      used to determine independent risk factors for developing a negative sagittal
      balance (SVA<-10 mm) following adult spinal deformity correction. Results: We
      reviewed 8 patients in group 1, 9 patients in group 2, and 25 patients in group
      3. The average postoperative SVA for group 1, group 2, and group 3 were -30.99,
      +3.67, and +55.56 mm, respectively. There was a trend toward higher upper
      instrumented vertebra (UIV) in group 1 (T2) compared with group 2 (T10) and group
      3 (T9) (P = .05). A trend toward lower preoperative SVA in groups 1 and 2
      compared with group 3 was also seen (+53.36 vs +71.73 vs +122.80 mm) (P = .06).
      Finally, we found a trend toward lower body mass index in group 1 compared with
      groups 2 and 3 (24.71 vs 25.92 vs 29.33 kg/m2) (P = .07). Based on multivariable
      regression, higher UIV was found to be a statistically significant independent
      predictor for developing a postoperative negative sagittal balance of <-10 mm (P
      = .02, odds ratio = 0.67). Conclusions: Our results demonstrate that a higher UIV
      may predispose patients undergoing adult spinal deformity correction to have a
      postoperative negative sagittal balance.

PMID- 29662746
TI  - The Predictive Value of Preoperative Health-Related Quality-of-Life Scores on
      Postoperative Patient-Reported Outcome Scores in Lumbar Spine Surgery.
AB  - Study Design: A single-center, retrospective cohort study. Objective: To predict
      patient-reported outcomes (PROs) using preoperative health-related quality-of
      life (HRQoL) scores by quantifying the correlation between them, so as to aid
      selection of surgical candidates and preoperative counselling. Methods: All
      patients who underwent single-level elective lumbar spine surgery over a 2-year
      period were divided into 3 diagnosis groups: spondylolisthesis, spinal stenosis,
      and disc herniation. Patient characteristics and health scores (Oswestry Low Back
      Pain and Disability Index [ODI], EQ-5D, and Short Form-36 version 2 [SF-36v2])
      were collected at 6 and 24 months and compared between the 3 diagnosis groups.
      Multivariate modelling was performed to investigate the predictive value of each
      parameter, particularly preoperative ODI and EQ-5D, on postoperative ODI and EQ
      5D scores for all the patients. Results: ODI and EQ-5D at 6 and 24 months
      improved significantly for all patients, especially in the disc herniation group,
      compared to the baseline. The magnitude of improvement in ODI and EQ-5D was
      predictable using preoperative ODI, EQ-5D, and SF-36v2 Mental Component Score. At
      6 months, 1-point baseline ODI predicts for 0.7-point increase in changed ODI,
      and a 0.01-point increase in baseline EQ-5D predicts for 0.01-point decrease in
      changed EQ-5D score. At 24 months, 1-point baseline ODI predicts for 1-point
      increase in changed ODI, and a 0.01-point increase in baseline EQ-5D predicts for
      0.009-point decrease in changed EQ-5D. A younger age is shown to be a positive
      predictor of ODI at 24 months. Conclusions: Poorer baseline health scores predict
      greater improvement in postoperative PROs at 6 and 24 months after the surgery.
      HRQoL scores can be used to decide on surgery and in preoperative counselling.

PMID- 29662748
TI  - National Trends for Primary and Revision Lumbar Disc Arthroplasty Throughout the
      United States.
AB  - Study Design: Retrospective database study. Objectives: Analysis of economic and
      demographic data concerning lumbar disc arthroplasty (LDA) throughout the United
      States to improve value-based care and health care utilization. Methods: The
      National Inpatient Sample database was queried for patients who underwent primary
      or revision LDA between 2005 and 2013. Demographic and economic data included
      total surgeries, costs, length of stay, and frequency of routine discharge. The
      National Inpatient Sample database represents a 20% sample of discharges from US
      hospitals weighted to provide national estimates. Results: Primary LDA decreased
      86% from 3059 to 420 from 2005 to 2013. The mean total cost of LDA increased 33%
      from $17 747 to $23 804. The mean length of stay decreased from 2.8 to 2.4 days.
      The mean routine discharge (home discharge without visiting nursing care)
      remained constant at 91%. Revision procedures (removal, supplemental fixation, or
      reoperation at the treated level) declined 30% from 194 to 135 cases over the
      study period. The mean revision burden, defined as the ratio of revision
      procedures to the sum of primary and revision procedures, was 12% (range 6% to
      24%). The mean total cost of revisions ranged from $12 752 to $22 282.
      Conclusions: From 2005 to 2013, primary LDA significantly declined in the United
      States by 86% despite several studies pointing to improved efficacy and cost
      efficiency. This disparity may be related to a lack of surgeon reimbursement from
      insurance companies. Congruently, the number of revision LDA cases has declined
      30%, while revision burden has risen from 6% to 24%.

PMID- 29662747
TI  - Nutritional Insufficiency as a Predictor for Adverse Outcomes in Adult Spinal
      Deformity Surgery.
AB  - Study Design: Retrospective analysis of prospectively collected data. Objective:
      The effect of malnutrition on outcomes after general surgery has been well
      reported in the literature. However, there is a paucity of data on the effect of
      malnutrition on postoperative complications during adult deformity surgery. The
      study attempts to explore and quantify the association between hypoalbuminemia
      and postoperative complications. Methods: A retrospective cohort analysis was
      performed on the American College of Surgeons National Surgical Quality
      Improvement Program (ACS NSQIP) database from 2010 to 2014. Patients (>=18 years
      of age) from the NSQIP database undergoing adult deformity surgery were separated
      into cohorts based serum albumin (<3.5 or >3.5 g/dL). Chi-square and multivariate
      logistic regression models were used to identify independent risk factors.
      Results: A total of 2236 patients met the inclusion criteria for the study, of
      which 2044 (91.4%) patients were nutritionally sufficient while 192 (8.6%)
      patients were nutritionally insufficient. Multivariate logistic regressions
      revealed nutritional insufficiency as a risk factors for mortality (odds ratio
      [OR] = 15.67, 95% confidence interval [CI] = 6.01-40.84, P < .0001), length of
      stay >=5 days (OR = 2.22, 95% CI = 1.61-3.06, P < .0001), any complications (OR =
      1.82, 95% CI = 1.31-2.51, P < .0001), pulmonary complications (OR = 2.29, 95% CI
      = 1.29-4.06, P = .005), renal complications (OR = 2.71, 95% CI = 1.05-7.00, P =
      .039), and intra-/postoperative red blood cell transfusion (OR = 1.52, 95% CI =
      1.08-2.12, P = .015). Conclusions: This study demonstrates that preoperative
      hypoalbuminemia is a significant and independent risk factor for postoperative
      complications, 30-day mortality, and increased length of hospital in patients
      undergoing adult deformity surgery surgery. Nutritional status is a modifiable
      risk factor that can potentially improve surgical outcomes after adult deformity
      surgery.

PMID- 29662749
TI  - Adverse Events Following Cervical Disc Arthroplasty: A Systematic Review.
AB  - Study Design: Systematic review. Objectives: Cervical arthroplasty is an
      increasingly popular treatment of cervical radiculopathy and myelopathy. An
      understanding of the potential adverse events (AEs) is important to help both
      clinicians and patients. We sought to provide a comprehensive systematic review
      of the AEs reported in all randomized controlled trials (RCTs) of cervical disc
      arthroplasty in an attempt to characterize the quality of reporting. Methods: We
      conducted a systematic review of MEDLINE and Web of Science for RCTs of cervical
      disc arthroplasty reporting AEs. We reported the most frequently mentioned AEs,
      including dysphagia/dysphonia, vascular compromise, dural injury, and infections.
      We recorded the presence of industry funding and scored the quality of collection
      methods and reporting of AEs. Results: Of the 3734 identified articles, 29
      articles met full inclusion criteria. The quality of AE reporting varied
      significantly between studies, and a combined meta-analysis was not feasible. The
      29 articles covered separate 19 RCTs. Eight studies were US Food and Drug
      Administration (FDA) investigational device exemption (IDE) trials. Rates were
      recorded for the following AEs: dysphagia/dysphonia (range = 1.3% to 27.2%),
      vascular compromise (range = 1.1% to 2.4%), cervical wound infection (range =
      1.2% to 22.5%), and cerebrospinal fluid leak (range = 0.8% to 7.1%). Conclusions:
      There is a lack of consistency in reporting of AEs among RCTs of cervical
      arthroplasty. FDA IDE trials scored better in AE event reporting compared to
      other studies. Standardized definitions for AEs and standardized data collection
      methodology are needed to improve future studies.

PMID- 29662750
TI  - Return to Play in Adolescent Athletes With Symptomatic Spondylolysis Without
      Listhesis: A Meta-Analysis.
AB  - Study Design: Meta-analysis. Objectives: To assess return to play (RTP) rates in
      adolescent athletes with lumbar spondylolysis without spondylolisthesis treated
      conservatively or operatively. Methods: A review of Medline, EMBASE, and Cochrane
      Reviews was performed. The pooled results were performed by calculating the
      effect size based on the logit event rate. Studies were weighted by the inverse
      of the variance. Confidence intervals were reported at 95%. Heterogeneity was
      assessed using the Q statistic and I2 value. Results: The initial literature
      search resulted in 724 articles, of which 29 were deemed relevant on abstract
      review. Overall, 11 studies provided data for 376 patients with a pars
      interarticularis defect. Return to athletic competition, based on logit event
      rate, was found to be statistically favored after both nonoperative and operative
      treatment (92.2% vs 90.3%). There was no heterogeneity noted among the studies
      reporting nonoperative treatment (Q value of 4.99 and I2 value of 0). There was
      mild heterogeneity within the operative studies (Q value of 3.54 and I2 value of
      15.18). Conclusions: Adolescent athletes RTP 92.2% of the time with nonoperative
      management, compared with 90.3% when treated operatively, though both treatment
      groups strongly favor RTP. As this is the first study to pool results of all
      relevant literature, it provides strong evidence to guide decision making and
      help manage expectations in this unique patient population.

PMID- 29662751
TI  - Blood Transfusion and Postoperative Infection in Spine Surgery: A Systematic
      Review.
AB  - Study Design: Systematic review. Objectives: Allogeneic blood transfusion-related
      immunomodulation may relatively suppress the immune system, heightening the risk
      of infection following spine surgery. This systematic review seeks to determine
      whether allogeneic blood transfusion increases the risk of postoperative
      infection and whether there are any factors that modify this association.
      Methods: PubMed, Cochrane Central Register of Controlled Trials, and reference
      lists from included studies were searched from inception to April 20, 2017 to
      identify studies examining the risk of infection following allogeneic blood
      transfusion in adult patients receiving surgery for degenerative spine disease.
      Results: Eleven retrospective cohort or case-control studies, involving 8428
      transfusion patients and 43 242 nontransfusion patients, were identified as
      meeting the inclusion criteria. Regarding surgical site infection (SSI), the
      results were mixed with roughly half reporting a significant association. There
      was an association between allogeneic transfusion and urinary tract infection
      (UTI) and any infection, but not respiratory tract infection. There was no
      statistical modifying effect of lumbar versus thoracic surgery on the association
      of allogeneic transfusion and SSI, though subgroup analyses in 3 of 4 studies
      reported a statistical association between transfusion and postoperative
      infections, including SSI, UTI, and any infection within the lumbar spine.
      Conclusions: This systematic review failed to find a consistent association
      between allogeneic transfusion and postoperative infection in spine surgery
      patients. However, these studies were all retrospective with a high or moderately
      high risk of bias. To properly examine this association an observational
      prospective study of sufficient power, estimated as 2400 patients, is required.

PMID- 29662752
TI  - Editorial Perspective.

PMID- 29662753
TI  - 2017 Reviewer Thank You.

PMID- 29662754
TI  - Magnesium-based implants: Beyond fixators.
AB  - : The mystery behind magnesium-induced bone formation is revealed by linking the
      neuropeptide(s) from sensory nerves with the osteogenic differentiation of stem
      cells in the periosteum. Zhang and colleagues' study sheds light on the
      development of magnesium pills or calcitonin gene-related peptide-delivery system
      for the prevention or treatment of osteoporosis. The translational potential of
      this article: For the first time, magnesium is shown to be beneficial for
      fracture healing at the weight-bearing site. In addition, calcitonin gene-related
      peptide-delivery system will also be another translational direction, as the
      promotive role of calcitonin gene-related peptide in fracture healing is
      supportive. These cost-effective and innovative treatment approaches will
      definitely bring a reduction not only in the suffering of patients, but also in
      the economic burden for their families and our society.

PMID- 29662755
TI  - CYR61-An angiogenic biomarker to early predict the impaired healing in diaphyseal
      tibial fractures.
AB  - Background: Angiogenesis is a prerequisite for fracture repair, whereas
      insufficient blood supply is likely to result in impaired healing. In the present
      study, we aimed to determine the correlation of simple tibial fracture healing
      outcome with serial estimation of CYR61 expressions in the early phase of
      healing. Methods: In total, 107 adult fractured patients and 97 healthy controls
      were analysed. Peripheral blood samples were taken from controls (at once) and
      fractured patients at 4th, 7th, 10th, 15th, 20th and 28th days of post-fracture
      follow-ups to quantify the CYR61 mRNA and protein expression by qRT-PCR and
      Western blotting assay, respectively. Clinic-radiological follow-up was done at
      6th, 10th, 16th, 20th, and 24th weeks of post-fracture follow-ups using RUST
      scores to analyse the fracture healing progression and their final outcomes.
      Results: By considering controls as Group I (n = 97), as per the clinico
      radiological status at 24th week, fracture patients were divided into two groups:
      Group II (normal healing, n = 91) and Group III (impaired healing, n = 16). Both
      CYR61 mRNA and protein expressions were lower (baseline) in Group I than in
      Groups II and III; however, a significant difference was observed only with the
      Group II. In both groups, expressions of CYR61 mRNA as well as protein gradually
      upregulated from the baseline to a peak and then declined. Both, the CYR61 mRNA
      as well as protein expressions were significantly higher at all follow-ups in
      Group II than in Group III. Mean RUST scores between Group II and Group III
      showed a significant statistical difference at each follow-up. Significant
      correlation was found between the CYR61 expressions and the RUST score (fracture
      healing progression). Conclusion: We conclude that CYR61 expression provides an
      early prediction of the healing outcomes of simple diaphyseal tibial fractures.
      The translational potential of this article: Such an approach would benefit not
      only the patients' wellbeing but also the entire health care system in terms of
      the cost implications associated with long lasting treatment interventions and
      hospitalisation. However, the authors recommend further multicentric study with a
      large sample size to increase the validity, reliability, and generalisability of
      our observation and inferences.

PMID- 29662756
TI  - Effect of capsaicin-sensitive sensory neurons on bone architecture and mechanical
      properties in the rat hindlimb suspension model.
AB  - Background/Objective: The participation of sensory neural regulation in bone
      metabolism has been widely studied. However, the physiological role of sensory
      neural regulation in the functional adaptation to weight bearing is not clear.
      This study was conducted to investigate the effect of capsaicin-induced sensory
      neuron lesions on cancellous architecture properties in a hindlimb suspension
      (HLS) model. Methods: Thirty-two female rats were randomly assigned to four
      groups. Groups b and d underwent systemic capsaicin treatment, whereas Groups a
      and c were treated with vehicle. Then, Groups c and d were subjected to HLS,
      whereas Groups a and b were allowed hindlimbs full loading. The proximal
      trabecular and mid-shaft cortical bone structure were evaluated via microcomputed
      tomography, and the biomechanical properties of the tibial mid-shaft were
      assessed using the four-point bending test. Results: The trabecular bone volume
      was reduced by 40% and 50% in Groups b and c, respectively, and was also reduced
      significantly in Group d. Trabecular thickness and trabecular separation in Group
      b were not significantly different from those of Group a. The cortical bone area
      fraction showed no significant difference among all groups. Compared with Group
      a, the ultimate strength in Group b decreased by 20.3%, whereas it did not change
      significantly in Group c. Conclusion: The results suggest that capsaicin
      sensitive sensory neurons play an important role in bone modelling. The effect of
      capsaicin is similar to HLS. However, HLS has no add-on effect to capsaicin in
      the reduction of bone density and mechanical properties.Translational potential
      of this article: This study gives clues to the function of sensory neurons in
      bone modelling.

PMID- 29662757
TI  - Bedside to bench and back to bedside: Translational implications of targeted
      intervertebral disc therapeutics.
AB  - Spinal pain and associated disability is a leading cause of morbidity worldwide
      that has a strong association with degenerative disc disease (DDD). DDD can begin
      in early-late adolescence and has a variable course. Biologically based therapies
      to treat DDD face significant challenges posed by the unique milieu of the
      environment within the intervertebral discs. Many potential promising therapies
      are still in the early stages of development with a hostile microenvironment
      within the disc presenting unique challenges. The translational potential of this
      article: Patient selection, reasonable therapeutic goals, approach, and timing
      will need to be discerned in order to successfully translate potential
      therapeutics.

PMID- 29662758
TI  - Neutrophil-to-lymphocyte ratio shows faster changing kinetics than C-reactive
      protein after total hip and knee arthroplasty.
AB  - Background: Total hip arthroplasty (THA) and total knee arthroplasty (TKA) induce
      inflammatory reactions, which can be described by changes in the neuroendocrine,
      cellular, protein, and cytokine systems. The aim of this study was to document
      the normal distribution pattern of the neutrophil-to-lymphocyte ratio (NLR) after
      THA and TKA and to compare it with postoperative C-reactive protein (CRP)
      patterns. Methods: Changes in serum CRP levels, neutrophil count, and lymphocyte
      count were measured before and during the first 5 postoperative days in a
      prospective study performed on 387 patients undergoing total hip or knee
      arthroplasty. Results: Mean CRP levels in patients undergoing THA were 7.7 mg/L,
      184.8 mg/L, and 115.9 mg/L, respectively, at Days 0, 3 and 5. The mean NLR of
      patients undergoing THA was 2.9, 3.6, and 2.7, respectively, at Days 0, 3, and 5.
      Mean CRP levels in patients undergoing TKA were 7.8 mg/L, 192.6 mg/L, and 108.6
      mg/L, respectively, at Days 0, 3 and 5. The mean NLR of patients undergoing TKA
      was 2.8, 3.4, and 2.6, respectively, at Days 0, 3, and 5. When comparing the
      preoperative value and the Day 3 value, CRP levels increased more than the NLR
      (almost a 24-fold increase in mean CRP values vs. a 1.2-fold increase in mean NLR
      values). In both groups, the NLR returned to preoperative values by the 5th
      postoperative day. Conclusions: The present study demonstrated a significant
      elevation in CRP levels and the NLR following THA and TKA. In both groups, the
      NLR showed a faster kinetics pattern than CRP levels in response to surgical
      trauma.The translational potential of this article: We describe results of the
      use of the NLR, as compared to a routinely used marker, CRP, as advantageous in
      clinical setting due to faster dynamics of change. Integrating the NLR in
      clinical practice seems easy and without extra cost.

PMID- 29662759
TI  - Investigation of bioeffects of G protein-coupled receptor 1 on bone turnover in
      male mice.
AB  - Maintenance of healthy bone quality and quantity requires a well-coordinated
      balance between bone formation by osteoblasts and bone resorption by osteoclasts.
      Chemerin is a novel adipokine with known functions such as regulating immunity
      and energy homeostasis through activation of chemokine-like receptor 1 (CMKLR1).
      G protein-coupled receptor 1 (GPR1) is the second mammalian chemerin receptor
      with similar binding affinity as CMKLR1. In male GPR1-/- mice, a phenotype with
      significantly low bone mineral density was observed. We hypothesise that GPR1
      might participate the process of bone remodelling. In this study, we investigated
      the role of GPR1 in regulating bone mass maintenance in male mice, and for the
      first time, revealed that GPR1-/- male mice manifested seriously trabecular bone
      loss and lower serum testosterone levels compared to the wild type animals.
      Accordingly, the mRNA expression of biomarkers related to both osteoblast
      [collagen type I alpha 2 (Col1A2), osteocalcin (OCN)] and osteoclast [tartrate
      resistant acid phosphatase (TRAP), Cathepsin K, NFATc1] were significantly
      decreased or increased in GPR1-/- mice relative to the wild type, respectively.
      However, other osteogenic markers, Osterix and ALP levels, were increased.
      Microcomputed tomography scanning and histological analyses proved that there was
      a myriad of trabecular bone loss in GPR1-/- mice. In the meantime, GPR1-/- mice
      presented a significant decrease in serum testosterone level. Taken together,
      these findings suggested that chemerin-GPR1 signalling might be directly or
      indirectly communicated with testosterone synthesis on bone turnover regulation.
      Further detailed studies are required to unveil how chemerin-GPR1 participates in
      bone metabolism. The translational potential of this article: More studies and
      knowledge about GPR1 regulating function in bone turnover might supply a novel
      therapeutic target for osteoporosis in the future.

PMID- 29662760
TI  - Macrophages and bone inflammation.
AB  - Bone metabolism is tightly regulated by the immune system. Accelerated bone
      destruction is observed in many bone diseases, such as rheumatoid arthritis,
      fracture, and particle-induced osteolysis. These pathological conditions are
      associated with inflammatory responses, suggesting the contribution of
      inflammation to bone destruction. Macrophages are heterogeneous immune cells and
      are polarized into the proinflammatory M1 and antiinflammatory M2 phenotypes in
      different microenvironments. The cytokines produced by macrophages depend on the
      macrophage activation and polarization. Macrophages and macrophage-derived
      cytokines are important to bone loss in inflammatory bone disease. Recent studies
      have shown that macrophages can be detected in bone tissue and interact with bone
      cells. The interplay between macrophages and bone cells is critical to bone
      formation and repair. In this article, we focus on the role of macrophages in
      inflammatory bone diseases, as well as discuss the latest studies about
      macrophages and bone formation, which will provide new insights into the
      therapeutic strategy for bone disease.

PMID- 29662762
TI  - Local administration of Trolox, a vitamin E analog, reduced tendon adhesion in a
      chicken model of flexor digitorum profundus tendon injury.
AB  - Background: Hand flexor tendon injuries are compromised with tendon adhesion.
      Tendon adhesion forms between flexor tendon and tendon sheath, reduces the range
      of motion of fingers, and affects their function. Oxidative stress is increased
      in flexor tendon after injury and might play a role in tendon adhesion formation.
      Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid), a water-soluble
      analog of vitamin E, is antioxidative. Trolox reduced oxidative stress and the
      expression of fibrotic cytokines in the bile gut ligation animal model. Vitamin C
      and Trolox are strong antioxidants, but they might also have prooxidant
      properties. The prooxidant properties of vitamin C and Trolox are different. In
      this study, our aim was to determine the effect of Trolox in reducing tendon
      adhesion formation. Methods: Flexor digitorum profundus tendon injury was induced
      in 54 Kai-Mei Chicken according to a well-established protocol. After wound
      closure, an injection of 50 MUL saline, 10mM Trolox, or 100mM Trolox was
      administered into the wound area. At 2 weeks or 6 weeks after the surgery,
      chicken feet were harvested for gliding test, high-resolution ultrasound
      measurement on a fibrotic area, and histology. Results: At Week 2 after the
      surgery, Trolox has no effect on the flexion angle and gliding resistance,
      whereas a significant improvement was observed in the flexion angle and gliding
      resistance in the Trolox-treated groups at Week 6. However, no dose response was
      observed. In the ultrasound measurement, there was no significant difference in
      the fibrotic mass in the Trolox-treated group as compared to the saline group at
      Week 2. At Week 6, fibrotic mass was significantly reduced in both Trolox-treated
      groups. From the histological examination, the Trolox-treated groups presented a
      higher cellularity at Week 2 as compared to the saline group, and reduced
      fibrosis and adhesion at Week 6. Conclusion: Our results suggest that local
      administration of Trolox can reduce tendon adhesion, and a higher dose of Trolox
      did not have negative effects. Clinical Significance: Trolox solution might be
      feasible to reduce tendon adhesion via intraoperative injection at the wound area
      during tendon repair.

PMID- 29662761
TI  - Inflammation and age-associated skeletal muscle deterioration (sarcopaenia).
AB  - : Ageing is accompanied by chronic inflammatory responses due to elevated
      circulatory inflammatory cytokine production. Several inflammatory cytokines have
      been shown to be responsible for a decrease in muscle mass. However, little is
      known about the possible relationship between inflammation and sarcopaenia. This
      review aims to summarise the existing evidence about inflammation and
      sarcopaenia. Sarcopaenia is defined as an age-related decrease of muscle mass
      and/or muscle strength; it is caused by multiple factors, such as skeletal muscle
      atrophy, neuromuscular junction degeneration, hormone imbalance, cytokine
      imbalance, protein synthesis and proteolysis. Several inflammatory cytokines have
      been considered to promote muscle loss; C-reactive protein levels are
      significantly upregulated in sarcopaenia and sarcopenic obesity, and high levels
      of interleukin-6 are associated with reduced muscle mass and muscle strength (the
      administration of interleukin-6 could lead to a reduction in muscle mass). Up
      regulation of tumour necrosis factor-alpha expression is also related to the
      development of sarcopaenia. Signalling pathways, such as protein kinase
      B/mammalian target of rapamycin, Janus kinase/signal transducer and activator of
      transcription-5 and signal transducer and activator of transcription 3
      signalling, involved in muscle metabolism are regulated by insulin-like growth
      factor-1, tumour necrosis factor-alpha and interleukin-6 respectively. In
      conclusion, the inflammatory cytokines produced during chronic inflammation due
      to ageing, may influence their respective related pathways, thus leading to age
      related muscle deterioration. The translational potential of this article: This
      review can provide more information for sarcopaenia medicine research in terms of
      anti-inflammation therapy.

PMID- 29662763
TI  - Inflammation and the musculoskeletal system.

PMID- 29662764
TI  - In vitro biomechanical evaluation of tri-condylar total knee arthroplasty with
      posterior release for restoration of full extension.
AB  - Background/Objective: The continuous improvement of knee function during deep
      flexion remains a challenge in total knee arthroplasty. Tri-condylar total knee
      arthroplasty has been designed to achieve this goal. However, the introduction of
      a third nonanatomic spherical condyle might prevent the joint from reaching full
      extension due to posterior soft tissue tightening. This study aimed to address
      these issues related to soft tissue tightening and full extension limitation.
      Methods: Biomechanical tests were performed on six cadaveric specimens of the
      entire lower extremities. The tri-condylar design was compared with a posterior
      cruciate sacrificing design of the same shape without the ball structure. Knee
      joint kinematics was measured, including the extension and flexion angles, the
      extension balance, and the extension gap. The test was repeated after release of
      the medial and lateral posterior intercondylar soft tissues at a safe distance
      from the popliteal artery and nerves. Results: Both designs resulted in a knee
      flexion angle up to ~130 degrees . The tri-condylar design showed an extension
      angle of -11.2 +/- 5.4 degrees , which was a significantly greater limitation
      than that obtained with the cruciate sacrificing design (-3.8 +/- 4.7 degrees ; p
      = 0.047). Moreover, the extension angle of the tri-condylar design was
      significantly improved after the release of posterior intercondylar soft tissues
      (-0.1 +/- 6.7 degrees ; p = 0.028). Conclusion: The tri-condylar design
      efficiently allowed the full extension by the release of posterior intercondylar
      soft tissues at a safe distance from the popliteal artery and nerves.

PMID- 29662765
TI  - A wearable exoskeleton suit for motion assistance to paralysed patients.
AB  - Background/Objective: The number of patients paralysed due to stroke, spinal cord
      injury, or other related diseases is increasing. In order to improve the physical
      and mental health of these patients, robotic devices that can help them to regain
      the mobility to stand and walk are highly desirable. The aim of this study is to
      develop a wearable exoskeleton suit to help paralysed patients regain the ability
      to stand up/sit down (STS) and walk. Methods: A lower extremity exoskeleton named
      CUHK-EXO was developed with considerations of ergonomics, user-friendly
      interface, safety, and comfort. The mechanical structure, human-machine
      interface, reference trajectories of the exoskeleton hip and knee joints, and
      control architecture of CUHK-EXO were designed. Clinical trials with a paralysed
      patient were performed to validate the effectiveness of the whole system design.
      Results: With the assistance provided by CUHK-EXO, the paralysed patient was able
      to STS and walk. As designed, the actual joint angles of the exoskeleton well
      followed the designed reference trajectories, and assistive torques generated
      from the exoskeleton actuators were able to support the patient's STS and walking
      motions. Conclusion: The whole system design of CUHK-EXO is effective and can be
      optimised for clinical application. The exoskeleton can provide proper assistance
      in enabling paralysed patients to STS and walk.

PMID- 29662766
TI  - Clinical validation of a body-fixed 3D accelerometer and algorithm for activity
      monitoring in orthopaedic patients.
AB  - Background/Objective: Activity is increasingly being recognized as a highly
      relevant parameter in all areas of healthcare for diagnosis, treatment, or
      outcome assessment, especially in orthopaedics where the movement apparatus is
      directly affected. Therefore, the aim of this study was to develop, describe, and
      clinically validate a generic activity-monitoring algorithm, satisfying a
      combination of three criteria. The algorithm must be able to identify, count, and
      time a large set of relevant daily activities. It must be validated for
      orthopaedic patients as well as healthy individuals, and the validation must be
      in a setting that mimics free-living conditions. Methods: Using various technical
      solutions, such as a dual-axis approach, dynamic inclinometry (hip flexion), and
      semiautomatic calibration (gait speed), the algorithms were designed to count and
      time the following postures, transfers, and activities of daily living:
      resting/sitting, standing, walking, ascending and descending stairs, sit-stand
      transitions, and cycling. In addition, the number of steps per walking bout was
      determined. Validation was performed with healthy individuals and patients who
      had undergone unilateral total joint arthroplasty, representing a wide spectrum
      of functional capacity. Video observation was used as the gold standard to count
      and time activities in a validation protocol approaching free-living conditions.
      Results: In total 992 and 390 events (activities or postures) were recorded in
      the healthy group and patient group, respectively. The mean error varied between
      0% and 2.8% for the healthy group and between 0% and 7.5% for the patient group.
      The error expressed in percentage of time varied between 2.0% and 3.0% for both
      groups. Conclusion: Activity monitoring of orthopaedic patients by counting and
      timing a large set of relevant daily life events is feasible in a user- and
      patient-friendly way and at high clinical validity using a generic three
      dimensional accelerometer and algorithms based on empirical and physical methods.
      The algorithms performed well for healthy individuals as well as patients
      recovering after total joint replacement in a challenging validation set-up. With
      such a simple and transparent method real-life activity parameters can be
      collected in orthopaedic practice for diagnostics, treatments, outcome
      assessment, or biofeedback.

PMID- 29662767
TI  - Reconstruction of the lateral tibia plateau fracture with a third triangular
      support screw: A biomechanical study.
AB  - Background: Split fractures of the lateral tibia plateau in young patients with
      good bone quality are commonly treated using two minimally invasive percutaneous
      lag screws, followed by unloading of the knee joint. Improved stability could be
      achieved with the use of a third screw inserted either in the jail-technique
      fashion or with a triangular support screw configuration. The aim of this study
      was to investigate under cyclic loading the compliance and endurance of the
      triangular support fixation in comparison with the standard two lag-screw
      fixation and the jail technique. Methods: Lateral split fractures of type AO/OTA
      41-B1 were created on 21 synthetic tibiae and subsequently fixed with one of the
      following three techniques for seven specimens: standard fixation by inserting
      two partially threaded 6.5 mm cannulated lag screws parallel to each other and
      orthogonal to the fracture plane; triangular support fixation-standard fixation
      with one additional support screw at the distal end of the fracture at 30 degrees
      proximal inclination; and jail fixation-standard fixation with one additional
      orthogonal support screw inserted in the medial nonfractured part of the bone.
      Mechanical testing was performed under progressively increasing cyclic
      compression loading. Fragment displacement was registered via triggered
      radiographic imaging. Results: Mean construct compliance was 3.847 * 10-3 mm/N
      [standard deviation (SD) 0.784] for standard fixation, 3.838 * 10-3 mm/N (SD
      0.242) for triangular fixation, and 3.563 * 10-3 mm/N (SD 0.383) for jail
      fixation, with no significant differences between the groups (p = 0.525). The
      mean numbers of cycles to 2 mm fragment dislocation, defined as a failure
      criterion, were 12,384 (SD 2267) for standard fixation, 17,708 (SD 2193) for
      triangular fixation, and 14,629 (SD 5194) for jail fixation. Triangular fixation
      revealed significantly longer endurance than the standard one (p = 0.047).
      Conclusion: Triangular support fixation enhanced interfragmentary stability at
      the ultimate stage of dynamic loading. However, the level of improvement seems to
      be limited and may not legitimate the intervention with an additional third
      screw.

PMID- 29662769
TI  - Human and bovine spinal disc mechanics subsequent to trypsin injection.
AB  - Objective: To investigate the biomechanical effects of injections of a protease
      on the characteristics of bovine coccygeal and human lumbar disc motion segments.
      Methods: Mechanics of treated tissues were measured immediately after injection
      and 3 h after injection. Motion segments underwent axial rotation and flexion
      extension loading. Results: Stiffness and neutral zone parameters experienced
      significant changes over time, with bovine tissues more strongly affected than
      human cadaver tissues. This was true in both axial rotation and flexion
      extension. The treatment type significantly affected the neutral zone
      measurements in axial rotation. Hysteresis parameters were impacted by control
      injections. Conclusion: The extrapolation of bovine coccygeal motion testing
      results to human lumbar disc mechanics is not yet practical. The injected
      treatment may have a smaller impact on disc mechanics than time in testing.
      Viscoelasticity of human lumbar discs may be impacted by any damage to the
      annulus fibrosis induced by needlestick. The Translational Potential of this
      Article: Preclinical testing of novel spinal devices is essential to the design
      validation and regulatory processes, but current testing techniques rely on
      cadaveric testing of primarily older spines with essentially random amounts of
      disc degeneration. The present work investigates the viability of using trypsin
      injections to create a more uniform preclinical model of disc degeneration from a
      mechanics perspective, for the purpose of testing spinal devices. Such a model
      would facilitate translation of new spinal technologies to clinical practice.

PMID- 29662768
TI  - Lumbar degenerative spondylolisthesis epidemiology: A systematic review with a
      focus on gender-specific and age-specific prevalence.
AB  - The epidemiology of lumbar degenerative spondylolisthesis (DS) remains
      controversial. We performed a systematic review with the aim of gaining a better
      understanding of the prevalence of DS in the general population. The results
      showed that the prevalence of DS is very gender- and age-specific. Few women and
      men develop DS before they are 50 years old. After 50 years of age, both women
      and men begin to develop DS, with women having a faster rate of development than
      men. For elderly Chinese (>= 65 years, mean age: 72.5 years), large population
      based studies MsOS (Hong Kong, females: n = 2000) and MrOS (Hong Kong, males: n =
      2000) showed DS prevalence was 25.0% in women and 19.1% in men. The female:male
      (F:M) prevalence ratio was 1.3:1. The published data for MsOS (USA) and MrOS
      (USA) studies seem to show that elderly Caucasian Americans have a higher DS
      prevalence, being approximately 60-70% higher than elderly Chinese; however, the
      F:M prevalence ratio was similar to the elderly Chinese population. Patient data
      showed that female patients more often received surgical treatment than male and
      preliminary data showed the ratio of female to male patients receiving surgical
      treatment did not differ between Northeast Asians (Chinese, Japanese, and
      Korean), Europeans, and American Caucasians, being around 2:1 in the elderly
      population. The existing data also suggest that menopause may be a contributing
      factor for the accelerated development of DS in postmenopausal women. The
      translational potential of this article: A better understanding of epidemiology
      of lumbar degenerative spondylolisthesis can support patient consultation and
      treatment planning.

PMID- 29662770
TI  - Predicting the collapse of the femoral head due to osteonecrosis: From basic
      methods to application prospects.
AB  - Collapse of the femoral head is the most significant pathogenic complication
      arising from osteonecrosis of the femoral head. It is related to the disruption
      of the maintenance of cartilage and bone, and results in an impaired function of
      the vascular component. A method for predicting the collapse of the femoral head
      can be treated as a type of clinical index. Efforts in recent years to predict
      the collapse of the femoral head due to osteonecrosis include multiple methods of
      radiographic analysis, stress distribution analysis, finite element analysis, and
      other innovative methods. Prediction methods for osteonecrosis of the femoral
      head complications originated in Western countries and have been further
      developed in Asia. Presently, an increasing number of surgeons have chosen to
      focus on surgical treatments instead of prediction methods to guide more
      conservative interventions, resulting in a growing reliance on the more prevalent
      and highly effective total hip arthroplasty, rather than on more conservative
      treatments. In this review, we performed a literature search of PubMed and Embase
      using search terms including "osteonecrosis of femoral head," "prediction,"
      "collapse," "finite element," "radiographic images," and "stress analysis,"
      exploring the basic prediction method and prospects for new applications.

PMID- 29662772
TI  - Editorial for the clinical paper "Therapeutic effects analysis of percutaneous
      kyphoplasty for osteoporotic vertebral compression fractures: A multicentre study
      Huilin Yang et al."

PMID- 29662771
TI  - Therapeutic effects analysis of percutaneous kyphoplasty for osteoporotic
      vertebral compression fractures: A multicentre study.
AB  - Background: Percutaneous kyphoplasty (PKP), a minimally invasive treatment, has
      been widely used for osteoporotic vertebral compression fractures (OVCFs).
      Objective: To retrospectively analyse the therapeutic effects of PKP using a
      series of key techniques in a multicentre study. Methods: From May 2000 to
      December 2016, PKP was performed using a series of key techniques (puncture,
      reduction, and perfusion techniques) for the treatment of 4532 OVCF patients. The
      pain visual analog scale (VAS) and the Oswestry Disability Index (ODI)
      questionnaire prior to the operation, at postoperative Day 2, and at the last
      follow-up were analysed by paired t-test analysis. The leakage of bone cement was
      evaluated by postoperative radiography and/or computed tomography. Four-year
      survival was calculated at the last follow-up. Results: The average follow-up was
      63 months (1-116 months). The VAS score decreased from 8.9 (preoperative) to 2.3
      (2 days postoperative) to 1.9 (last follow-up). The ODI score of the patients
      decreased from 86.7 (preoperative) to 31.6 (2 days postoperative) to 25.3 (last
      follow-up). Both VAS score and ODI score improved significantly. The bone cement
      leakage rate was 3.5%, with no clinical symptoms. The 4-year survival rate was
      77.5%. Conclusion: This study suggests that PKP with key techniques would be an
      effective technique to treat OVCF with less risk and better therapeutic effect.
      Such diagnostic methods and surgical techniques lead to the development and
      progress of treatment for OVCF.The translational potential of this article: PKP
      with key techniques would be an effective technique to treat and lead to the
      development and progress of treatment for OVCF.

PMID- 29662773
TI  - Characteristics of bone biochemical indices in predicting secondary osteoporotic
      fracture after intertrochanteric fracture in elderly women.
AB  - Background: This study aimed to explore the characteristics of bone biochemical
      indices, including bone mineral density (BMD), metabolic markers in elderly women
      with osteoporotic intertrochanteric fracture and their relevance in secondary
      fracture. Methods: The standard for follow-up from 58 elderly women was
      established to analyse the BMD in the injured hip, healthy hip, and the vertebra
      at 1 week and 12 months after fracture. The serum levels of total procollagen
      type N-terminal propeptide (tPINP) and the age-related type I cross linked C
      telopeptide (beta-CTX) were recorded and compared between those patients with and
      without secondary fractures within 12 months. Results: Twelve months after
      fracture, the serum levels of tPINP and beta-CTX were significantly higher than
      the baseline values (p < 0.01). The tPINP baseline in patients with secondary
      fracture was significantly lower than that in the rest patients without secondary
      fracture (p < 0.01). The beta-CTX baseline was notably higher than that without
      secondary fracture (p < 0.01). BMD values of the three periods had no
      significantly difference. Conclusion: The serum levels of tPINP and beta-CTX are
      of great value in earlier and more sensitively reflecting the condition of bone
      turnover in body. Meanwhile, they can predict the subsequent fracture risk more
      accurately combined with a lower BMD. The Translational Potential of this
      Article: Besides BMD, bone microstructure and remodeling levels can be accurately
      measured by bone biochemical indices. The main objective of this research is to
      explore the change of BMD and the serum level of bone biochemical indices of
      elderly women who suffered unilateral intertrochanteric fracture within 12
      months. Simultaneously, with aim to better obtain bone remodeling level and
      predict more accurately the risk of a secondary osteoporotic fracture, bone
      biochemical indices of these patients, who undergo secondary osteoporotic
      fracture or not, are collected during follow-up and compared respectively.

PMID- 29662774
TI  - A novel gait-based synthesis procedure for the design of 4-bar exoskeleton with
      natural trajectories.
AB  - Background/Objective: Human walking involves the coordination of brain, nerves,
      and muscles. A disturbance in their coordination may result in gait disorder. The
      gait disorder may be treated through manually assisted gait training or with the
      aid of assistive devices/robotic devices. These robotic devices involve
      mechanisms which are synthesized using complex conventional procedures.
      Therefore, in this study, a new gait-based synthesis procedure is proposed, which
      simplifies the mechanism synthesis and helps to develop a mechanism which can be
      used in rehabilitation devices, bipeds, etc. Methods: This article presents a
      novel procedure for the synthesis of 4-bar linkage using the natural gait
      trajectories. As opposed to the conventional synthesis procedures, in this
      procedure, a global reference frame is considered, which allows the use of hip
      trajectory while moving. Moreover, this method is divided into two stages, and
      five precision points are considered on the hip trajectory in each stage. In the
      first stage, the 4-bar linkage is designed, thereafter, the configurations of the
      linkage for the remaining precision points are determined in the second stage.
      The proposed synthesis procedure reduces the complexity involved in the synthesis
      and helps in the simplification of the problem formulation. A two-stage
      optimization problem is formulated for minimizing the error between the generated
      and desired hip trajectories. Two nature-inspired algorithms are used for solving
      the optimization problem. The obtained best results are presented, and the
      designed linkage is simulated in MATLAB. Results: The best design of the linkage
      is obtained using particle swarm optimization. The trajectories generated by the
      designed linkage using the proposed methodology can accurately track the desired
      path, which indicates that designed linkage can achieve all the orientations
      required during walking. The positions of a whole lower limb at all the desired
      precision points are demonstrated by stick diagram for one gait. Conclusion: The
      proposed methodology has reduced the complexity of synthesis procedures and used
      optimization techniques to obtain a feasible design of the mechanism. The stick
      diagram of the designed mechanism obtained using the proposed method indicates
      that the designed mechanism can walk smoothly. Hence, the designed mechanism can
      be used in the rehabilitation devices. Furthermore, a conceptual design of an
      exoskeleton knee is also presented. The Translational Potential of this Article:
      Many hospitals and individuals have used the immobile and portable rehabilitation
      devices. These devices involve mechanisms, and the design of mechanism plays a
      vital role in the functioning of these devices; therefore, we have developed a
      new synthesis procedure for the design of the mechanism. Besides synthesis
      procedure, a mechanism is developed that can be used in the rehabilitation
      devices, bipeds, exoskeletons, etc., to benefit the society.

PMID- 29662776
TI  - Three-dimensional morphometric properties of rod- and plate-like trabeculae in
      adolescent cancellous bone.
AB  - Background/Objective: Despite many researches have been carried out on the three
      dimensional microarchitecture of cancellous bone, the morphometric properties of
      rod and plate trabeculae in adolescent cancellous bone have not yet been
      investigated. This study aimed to investigate three-dimensional morphometric
      properties of rod- and plate-like trabeculae in normal adolescent cancellous
      bone, and to compare them with adult cancellous bones to reveal morphometric
      changes from adolescence to adult life to obtain more insight into the
      subchondral bone adaptations during development and growth. Methods: This study
      included 23 normal human proximal tibiae. These tibiae were divided into three
      groups: adolescents (9-17 years, n = 6), young adults (18-24 years, n = 9), and
      adults (25-30 years, n = 8). From each tibia, six cubic cancellous bone samples
      (dimensions 8 * 8 * 8 mm3) were sawed from each medial and lateral condyle,
      yielding a total of 276 samples. These samples were scanned using micro computed
      tomography leading to three-dimensional cubic voxel sizes of 10.5 * 10.5 * 10.5
      MUm3. The morphometric parameters of individual rod- and plate-like trabeculae
      were calculated and compared among three age groups. Results: Significant
      differences in some morphometric parameters were revealed. The mean longitudinal
      length of rods was significantly greater in the adolescents than in the young
      adults. Plate volume density showed an increasing trend with age, although not
      significant. Trabeculae were more plate-like in adolescents in the medial condyle
      of adolescents than in the lateral condyle, and changed towards more plate-like
      trabeculae in the adults. The single best predictor for the mechanical properties
      was apparent density. Apparent density alone explained 59% variations in Young's
      modulus, 77% in ultimate stress and 34% in failure energy, respectively (all p <
      0.01). Morphometric parameters might improve this prediction. Conclusion: In
      conclusion, this study has reported for the first time the morphometric
      parameters of rod- and plate-like trabeculae in adolescent proximal tibial
      cancellous bone, which will improve our understanding of morphometric changes in
      individual trabeculae during development and growth. Furthermore, separate
      analysis of individual rods and plates may also help reveal disease-related
      morphometric changes beyond bone mineral density. The translational potential of
      this article: A thorough quantification of individual trabeculae during
      development and growth may help understand disease-related 3-D morphometric
      changes beyond bone mineral density.

PMID- 29662775
TI  - Relationship between heterotopic ossification and traumatic brain injury: Why
      severe traumatic brain injury increases the risk of heterotopic ossification.
AB  - Heterotopic ossification (HO) is a pathological phenomenon in which ectopic
      lamellar bone forms in soft tissues. HO involves many predisposing factors,
      including congenital and postnatal factors. Postnatal HO is usually induced by
      fracture, burn, neurological damage (brain injury and spinal cord injury) and
      joint replacement. Recent studies have found that patients who suffered from bone
      fracture combined with severe traumatic brain injury (S-TBI) are at a
      significantly increased risk for HO occurrence. Thus, considerable research
      focused on the influence of S-TBI on fracture healing and bone formation, as well
      as on the changes in various osteogenic factors with S-TBI occurrence. Brain
      damage promotes bone formation, but the exact mechanisms underlying bone
      formation and HO after S-TBI remain to be clarified. Hence, this article
      summarises the findings of previous studies on the relationship between S-TBI and
      HO and discusses the probable causes and mechanisms of HO caused by S-TBI. The
      translational potential of this article: A better understanding of the probable
      causes of traumatic brain injury-induced HO can provide new perspectives and
      ideas in preventing HO and may support to design more targeted therapies to
      reduce HO or enhance the bone formation.

PMID- 29662778
TI  - Comparisons of slice-encoding metal artifact correction and view-angle tilting
      magnetic resonance imaging and traditional digital radiography in evaluating
      chronic hip pain after total hip arthroplasty.
AB  - Purpose: The aims of this study were (1) to compare the areas of metal-induced
      artifacts and definition of periprosthetic structures between patients scanned
      with the slice-encoding metal artifact correction and view-angle tilting (SEMAC
      VAT) turbo-spin-echo (TSE) prototype and those scanned with the standard TSE
      magnetic resonance (MR) sequences and (2) to further clarify the superiority of
      the SEMAC-VAT MR imaging technique at detecting lesions in patients after total
      hip arthroplasty (THA), compared with digital radiography (DR). Materials and
      methods: A total of 38 consecutive patients who underwent THA were referred to MR
      imaging at our institution. All patients suffered from chronic hip pain
      postoperatively. Twenty-three patients of the 38 were examined with a 1.5-T MR
      scanner using a SEMAC-VAT TSE prototype and standard TSE sequence, and the
      remaining 15 patients were examined with the same 1.5-T MR scanner, but using the
      SEMAC-VAT TSE prototype only. The traditional DR imaging was also performed for
      all patients. Two radiologists then independently measured the area of metal
      induced artifacts and evaluated the definition of both the acetabular and femoral
      zones based on a three-point scale. Finally, the positive findings of chronic hip
      pain after THA based on SEMAC-VAT TSE MR imaging and traditional DR imaging were
      compared and analysed. Results: The areas of metal-induced artifacts were
      significantly smaller in the SEMAC-VAT TSE sequences than those in the standard
      TSE sequences for both the T1-weighted (p < 0.001) and T2-weighted (p < 0.001)
      turbo inversion recovery magnitude images. In addition, 28 patients showed a
      series of positive signs in the SEMAC-VAT images that were not observed in the
      traditional DR images. Conclusion: Compared with the standard TSE MR imaging,
      SEMAC-VAT MR imaging significantly reduces metal-induced artifacts and might
      successfully detect most positive signs missed in the traditional DR images.
      Translational potential of this article: The main objective of this research was
      to show that MR sequences from the SEMAC-VAT TSE prototype provide a significant
      advantage at detecting lesions in patients after THA because of the excellent
      soft-tissue resolution of the MR imaging. SEMAC-VAT MR can evaluate chronic hip
      pain after THA and determine the cause, which can help the clinician decide on
      whether a surgical revision is needed.

PMID- 29662777
TI  - Herbal Fufang Xian Ling Gu Bao prevents corticosteroid-induced osteonecrosis of
      the femoral head-A first multicentre, randomised, double-blind, placebo
      controlled clinical trial.
AB  - Background/Objective: This is a multicentre, randomised, double-blind, placebo
      controlled clinical trial to investigate the safety and efficacy of Chinese
      herbal Fufang Xian Ling Gu Bao (XLGB) with antiadipogenic compounds for the
      prevention of corticosteroid (CS)-induced osteonecrosis of femoral head (ONFH).
      Methods: Patients of both genders, aged between 18 and 65 years, with diseases
      such as systemic lupus erythematosus, nephrosis, dermatosis and rheumatoid
      arthritis indicated for CS treatment and who did not show magnetic resonance
      imaging of ONFH at baseline were recruited into the study and then randomised
      into either XLGB group (n = 129) with daily oral administration of XLGB or
      placebo group (n = 146). Results: Magnetic resonance imaging revealed a total of
      30 ONFH cases at 6 months after CS treatment, with 6.98% (9 of 129 cases) and
      14.4% (21 of 146 cases) in the XLGB group and placebo group, respectively, (p <
      0.05), i.e., a 2-fold significantly less ONFH identified in the XLGB treatment
      group. Blood tests suggested that XLGB significantly inhibited the elevation of
      activated protein C resistance induced by CS treatment. Conclusion: This is the
      first multicentre clinical study to demonstrate that the antiadipogenic compounds
      rich herbal Fufang (formula) XLGB is effective in preventing CS-associated ONFH
      in patients with immune-inflammatory diseases under CS treatment. The
      translational potential of this article: The translation potential of this
      clinical trial is that the initially officially approved clinical indication for
      XLGB for treatment of osteoporosis has been now also proven to be effective for a
      new clinical application.

PMID- 29662779
TI  - Finite element analysis of biomechanical effects of total ankle arthroplasty on
      the foot.
AB  - Background: Total ankle arthroplasty is gaining popularity as an alternation to
      ankle arthrodesis for end-stage ankle arthritis. Owing to the complex anatomical
      characteristics of the ankle joint, total ankle arthroplasty has higher failure
      rates. Biomechanical exploration of the effects of total ankle arthroplasty on
      the foot and ankle is imperative for the precaution of postoperative
      complications. The objectives of this study are (1) to investigate the
      biomechanical differences of the foot and ankle between the foot with total ankle
      arthroplasty and the intact foot and (2) to investigate the performance of the
      three-component ankle prosthesis. Methods: To understand the loading environment
      of the inner foot, comprehensive finite element models of an intact foot and a
      foot with total ankle arthroplasty were developed to simulate the stance phase of
      gait. Motion analysis on the model subject was conducted to obtain the boundary
      and loading conditions. The model was validated through comparison of plantar
      pressure and joint contact pressure between computational prediction and
      experimental measurement. A pressure mapping system was used to measure the
      plantar pressure during balanced standing and walking in the motion analysis
      experiment, and joint contact pressure at the talonavicular joint was measured in
      a cadaver foot. Results: Plantar pressure, stress distribution in bones and
      implants and joint contact loading in the two models were compared, and motion of
      the prosthesis was analysed. Compared with the intact foot model, averaged
      contact pressure at the medial cuneonavicular joint increased by 67.4% at the
      second-peak instant. The maximum stress in the metatarsal bones increased by
      19.8% and 31.3% at the mid-stance and second-peak instants, respectively. Force
      that was transmitted in three medial columns was 0.33, 0.53 and 1.15 times of
      body weight, respectively, at the first-peak, mid-stance and second-peak
      instants. The range of motion of the prosthetic ankle was constrained in the
      frontal plane. The lateral side of the prosthesis sustained higher loading than
      the medial side. Conclusion: Total ankle arthroplasty resulted in great increase
      of contact pressure at the medial cuneonavicular joint, making it sustain the
      highest contact pressure among all joints in the foot. The motion of the
      prosthesis was constrained in the frontal plane, and asymmetric loading was
      distributed in the bearing component of the ankle prosthesis in the mediolateral
      direction. The translational potential of this article: Biomechanical variations
      resulted from total ankle arthroplasty may contribute to negative postoperative
      outcomes. The exploration of the biomechanical performance in this study might
      benefit the surgeons in the determination of surgical protocols to avoid
      complications. The analysis of the performance of the ankle prosthesis could
      enhance the knowledge of prosthetic design.

PMID- 29662780
TI  - Distinct metabolic programs induced by TGF-beta1 and BMP2 in human articular
      chondrocytes with osteoarthritis.
AB  - Objectives: Cellular energy metabolism is important for the function of all
      tissues, including cartilage. Recent studies indicate that superficial and deep
      subpopulations of articular chondrocytes (ACs) have distinct metabolic profiles.
      At the cellular and molecular level, osteoarthritis (OA) is characterised by
      alteration from a healthy homoeostatic state towards a catabolic state. Several
      molecular pathways, including transforming growth factor beta (TGF-beta) and bone
      morphogenetic protein (BMP) signalling, have been identified as critical players
      in the pathogenesis and progression of OA. However, the manner in which these
      factors influence cellular energy metabolism in ACs is not well understood. This
      study investigates the effect of TGF-beta or BMP signalling on energy metabolism
      in human articular chondrocytes (hACs). Methods: ACs were isolated from residual
      macroscopically full thickness and intact cartilage from the femoral condyle of
      human samples obtained from patients with OA. ACs were treated with Vehicle
      (control), TGF-beta1 or BMP2 for 48-72 hours. Metabolic assays were performed to
      determine glucose consumption, lactate production and adenosine triphosphate
      (ATP) production, whereas the mitochondrial stress test was performed to
      determine oxygen consumption rate. Protein was isolated to assess translational
      activity and was evaluated using Western blot. Results: We showed that TGF-beta1,
      known to maintain chondrocyte homoeostasis, stimulated glycolysis by upregulating
      key glycolytic factors, such as glucose transporter 1 (Glut1) and hexokinase II,
      while reducing oxidative phosphorylation in hACs. In contrast, BMP2 enhanced
      mitochondrial metabolism and oxidative phosphorylation and had a minimal effect
      on key glycolytic regulators. Conclusions: Our data revealed distinct metabolic
      programs induced by TGF-beta1 and BMP2 in hACs, suggesting that the regulation of
      cellular metabolism may represent a new mechanism underlying the pathogenesis of
      OA. The translational potential of this article: The findings define the
      regulation of energy metabolism as a potential novel therapeutic approach for the
      treatment of OA.

PMID- 29662781
TI  - The effect of Chinese martial arts Tai Chi Chuan on prevention of osteoporosis: A
      systematic review.
AB  - Background/Objective: Tai Chi Chuan (TCC) is suggested to have beneficial effects
      on the musculoskeletal system. The aim of this systematic review is to evaluate
      the evidence of the effect of TCC on bone mineral density (BMD) and its potential
      for prevention of osteoporosis. Methods: A literature search was conducted using
      PubMed, Embase, and Cochrane databases from inception to January 2017. Randomized
      controlled studies, case-control trials, prospective cohort studies, and cross
      sectional studies which evaluated the effect of TCC on BMD were selected without
      any subject or language restriction. Results: Nine articles met the inclusion
      criteria, including seven randomized controlled trials (RCTs), one case-control
      trial (CCT), and one cross-sectional study, encompassing a total of 1222
      participants. Five studies showed statistically significant improvements in BMD
      after TCC, three studies showed nonsignificant intergroup differences, and one
      study provided no statistical evaluation of results. The studies with
      nonsignificant results tended to have a shorter total duration of TCC practice.
      Apart from dual-energy X-ray absorptiometry (DXA), two studies additionally used
      peripheral quantitative computed tomography (pQCT) which showed statistically
      significant positive effects of TCC on preventing osteoporosis. Conclusion: TCC
      is beneficial to BMD and may be a cost-effective and preventive measure of
      osteoporosis. This beneficial effect is better observed in long-term TCC
      practice. The translational potential of this article: The beneficial effect of
      TCC on BMD is suggested to be clinically translated to its potential for early
      rehabilitation and prevention of secondary osteoporosis in patients after
      surgical treatment of common osteoporotic fractures. The length of practicing
      TCC, the form and style of TCC, and the types of patient suitable for TCC are to
      be investigated in future studies.

PMID- 29662782
TI  - Quantitative analysis of T2 relaxation times of the patellofemoral joint
      cartilage 3 years after anterior cruciate ligament reconstruction.
AB  - Objective: To evaluate patient-specific patellofemoral joint (PFJ) cartilage 3
      years postoperatively using T2 mapping magnetic resonance imaging and the
      uninjured contralateral side as control. Hypothesis: The cartilage of the PFJ in
      the anterior cruciate ligament (ACL) reconstructed knees would show increased T2
      values compared to the uninjured contralateral knees at 3-year follow-up, and the
      femoral (trochlear) cartilage would be more susceptible than the patella in
      degeneration in ACL-reconstructed knees. Methods: Ten patients with clinically
      successful ACL-reconstructed knees were prospectively enrolled 3 years
      postoperatively. Sagittal images of both knees were obtained using T2 mapping.
      Cartilage over the medial, central, and lateral regions of the trochlea and
      patella was divided into superficial and deep regions. Average T2 values of the
      cartilage at each region of interest of the ACL-reconstructed and uninjured
      contralateral knees were compared for each individual patient. Results: Overall,
      the T2 values at the superficial layers of the medial and central trochlear
      cartilage of the ACL-reconstructed knees were significantly higher than those of
      the uninjured contralateral knees by 4.23 +/- 9.09 milliseconds (8.9%; p = 0.043)
      and 5.94 +/- 8.12 milliseconds (10.9%; p = 0.019), respectively. No significant
      difference was found in other cartilage areas of the trochlea and patella. In
      individual patient analysis, increased T2 values of ACL-reconstructed knees were
      found in all 10 patients in at least one superficial region and eight patients in
      at least one deep region of the trochlear cartilage, five patients in at least
      one superficial region, and eight patients in at least one deep region of the
      patellar cartilage. Conclusion: Despite a clinically satisfactory ACL
      reconstruction (with negative anteroposterior drawer and pivot shift tests), all
      patients showed at least one region with increased T2 value of the PFJ cartilage
      3 years after ACL reconstruction, especially at the medial compartment of the
      trochlear cartilage. The Translational Potential of this Article: Little data has
      been reported on PFJ cartilage condition after ACL reconstruction. This study
      could help develop noninvasive diagnostic methods for detection of early PFJ
      cartilage degeneration after ACL reconstruction.

PMID- 29662783
TI  - The impact of translational orthopaedic research: Journal of Orthopaedic
      Translation indexed in Science Citation Index Expanded.

PMID- 29662784
TI  - Clinical translation and application in orthopaedics.

PMID- 29662785
TI  - Hip geometry and femoral neck fractures: A meta-analysis.
AB  - Background: Several studies have reported hip geometry to predict the femoral
      neck fractures. However, they showed inconsistency. Objectives: To determine the
      association between hip geometry and femoral neck fractures. Methods: Published
      literature from PubMed and Embase databases (until May 25th, 2017) was searched
      for eligible publications. The information related to (1) name of first author;
      (2) year of publication; (3) country of origin; (4) sample size of cases and
      controls and (5) mean and standard deviation of cases and controls were
      extracted. The pooled odds ratios (ORs) and 95% confidence intervals (95% CIs)
      for the association between hip geometry and femoral neck fractures were assessed
      using random or fixed effect model. A Comprehensive Meta-analysis software,
      version 2.0, was used to analyse the data. Results: A total of 11 studies were
      included in this study. Our results showed that increase in hip axis length (OR
      95% CI = 1.53 [1.06-2.21], p = 0.025), femoral neck angle (OR 95% CI = 1.47 [1.01
      2.15], p = 0.044) and neck width (OR 95% CI = 2.68 [1.84-3.91], p < 0.001) was
      associated with the risk of femoral neck fractures, whereas we could not find the
      correlation between femoral neck axis length and the risk of femoral neck
      fractures. Conclusion: There is strong evidence that elevated hip axis length,
      femoral neck angle and neck width are the risk factor for femoral neck
      fractures.The Translational Potential of this Article: Determining the hip axis
      length, femoral neck angle and neck width that are most highly associated with
      femoral neck fracture may allow clinicians to more accurately predict which
      individuals are likely to experience femoral neck fractures in the future.

PMID- 29662786
TI  - Comparison of topical and intravenous administration of tranexamic acid for blood
      loss control during total joint replacement: Review of literature.
AB  - Purpose: Many randomised controlled trials and meta-analysis studies have
      presented the efficacy of tranexamic acid (TXA) without an increase of
      complications. However, questions still remain about the type of administration,
      optimal dose and secondary outcomes of TXA in total hip arthroplasty and total
      knee arthroplasty. The aim of this review is to summarise the existing
      information in literature concerning the pharmacological characteristics of TXA,
      forms, doses, types of application and contraindications for its use. Methods: A
      literature review containing 63 articles from the PubMed data starting from the
      first description of tranexamic acid until now was made in trying to present the
      existing information in a simple and effective way. Results: TXA leads to
      statistically significant reduction of peri and postoperative bleeding and in
      that way decreases blood transfusion rates and the infection risk. Topical and
      intravenous (IV) use of TXA revealed similar results, with no increase of deep
      venous thrombosis. Therefore, topical TXA could be a reasonable alternative in
      patients with contraindications for IV application of TXA. Conclusions: Blood
      loss control with TXA, a synthetic analogue of the amino acid lysine, may be an
      excellent and safe alternative to allogeneic blood transfusion after total hip
      arthroplasty and total knee arthroplasty. Further studies are needed to establish
      the efficacy of combined IV and topical administration of TXA with regard to
      diminishing blood loss and reducing hospital stay. The Translational Potential of
      this Article: This review briefly presents the pharmacological characteristics of
      TXA, forms, doses, types of application and contraindications for its use with
      regard to diminishing blood loss and reducing hospital stay for better
      therapeutic strategies in orthopaedics.

PMID- 29662787
TI  - Steroid-associated osteonecrosis animal model in rats.
AB  - Objective: Established preclinical disease models are essential for not only
      studying aetiology and/or pathophysiology of the relevant diseases but more
      importantly also for testing prevention and/or treatment concept(s). The present
      study proposed and established a detailed induction and assessment protocol for a
      unique and cost-effective preclinical steroid-associated osteonecrosis (SAON) in
      rats with pulsed injections of lipopolysaccharide (LPS) and methylprednisolone
      (MPS). Methods: Sixteen 24-week-old male Sprague-Dawley rats were used to induce
      SAON by one intravenous injection of LPS (0.2 mg/kg) and three intraperitoneal
      injections of MPS (100 mg/kg) with a time interval of 24 hour, and then, MPS (40
      mg/kg) was intraperitoneally injected three times a week from week 2 until
      sacrifice. Additional 12 rats were used as normal controls. Two and six weeks
      after induction, animals were scanned by metabolic dual energy X-ray
      absorptiometry for evaluation of tissue composition; serum was collected for bone
      turnover markers, Microfil perfusion was performed for angiography, the liver was
      collected for histopathology and bilateral femora and bilateral tibiae were
      collected for histological examination. Results: Three rats died after LPS
      injection, i.e., with 15.8% (3/19) mortality. Histological evaluation showed 100%
      incidence of SAON at week 2. Dual energy X-ray absorptiometry showed
      significantly higher fat percent and lower lean mass in SAON group at week 6.
      Micro-computed tomography (Micro-CT) showed significant bone degradation at
      proximal tibia 6 weeks after SAON induction. Angiography illustrated
      significantly less blood vessels in the proximal tibia and significantly more
      leakage particles in the distal tibia 2 weeks after SAON induction. Serum amino
      terminal propeptide of type I collagen and osteocalcin were significantly lower
      at both 2 and 6 weeks after SAON induction, and serum carboxy-terminal
      telopeptide was significantly lower at 6 weeks after SAON induction.
      Histomorphometry revealed significantly lower osteoblast surface and higher
      marrow fat fraction and oedema area in SAON group. Hepatic oedema appeared 2
      weeks after SAON induction, and lipid accumulation appeared in the liver of SAON
      rats 6 weeks after SAON induction. Conclusion: The present study successfully
      induced SAON in rats with pulsed injection of LPS and MPS, which was well
      simulating the clinical feature and pathology. Apart from available large animal
      models, such as bipedal emus or quadrupedal rabbits, our current SAON small model
      in rats could be a cost-effective preclinical experimental model to study body
      metabolism, molecular mechanism of SAON and potential drugs developed for
      prevention or treatment of SAON. The translational potential of this article: The
      present study successfully induced SAON in a small animal model in rats with
      pulsed injection of LPS and MPS. The evaluation protocols with typical
      histopathologic ON features and advanced evaluation approaches to identify the
      metabolic disorders of SAON could be used in future rat SAON studies. The SAON
      rat model is a suitable and cost-effective animal model to study molecular
      mechanism of SAON and potential drugs developed for prevention and treatment of
      SAON.

PMID- 29662789
TI  - Pie-crusting technique is effective and safe to release superficial medial
      collateral ligament for total knee arthroplasty.
AB  - Background: Pie-crusting technique is a damage-control soft tissue balance skill
      of total knee arthroplasty (TKA). The outcome of this technique to release
      lateral soft tissue is reasonable. A limited number of studies have focused on
      medial collateral ligament release with pie-crusting technique in the past years
      because of concerns about its efficacy and safety. Method: All cases underwent
      superficial medial collateral ligament (SMCL) release with either pie-crusting
      technique or traditional technique (39 knees in each group) between January 1,
      2014 and August 31, 2015. A comparison study between two techniques was
      performed; meanwhile, 23 patients (26 knees) in pie-crusting group were followed
      up. Data including knee function, radiographic result and complications were
      analysed. Results: Comparison study demonstrates that pie-crusting technique can
      achieve a comparable or even better effect of alignment correction. Data of
      follow-up patients are reasonable. The mean postoperative flexion contracture is
      1.2 +/- 3.6 degrees . The mean postoperative motion arrange is 104.0 +/- 14.4
      degrees . The mean postoperative hospital for special surgery knee score point is
      82.0 +/- 7.4 points. The mean postoperative femoral tibial angle is 172.4 +/- 2.0
      degrees . The level of joint line elevates around 2.1 +/- 1.9 mm. There are four
      knees that use brace after operation, and none of them present unstable knee. No
      severe complication has been reported, and most patients were satisfied with life
      quality. Conclusions: Using pie-crusting technique to release SMCL for TKA is
      effective and safe. The translational potential of this article: Although pie
      crusting technique has been used in TKA for years, it is seldom chosen to release
      medial collateral ligament, especially to release SMCL, which is a vital step of
      malalignment correction. This study aims to evaluate the efficacy and safety of
      this technique in total knee arthroplasty patients.

PMID- 29662788
TI  - Skeletal muscle regeneration is modulated by inflammation.
AB  - : Skeletal muscle regeneration is a complex process orchestrated by multiple
      steps. Recent findings indicate that inflammatory responses could play central
      roles in bridging initial muscle injury responses and timely muscle injury
      reparation. The various types of immune cells and cytokines have crucial roles in
      muscle regeneration process. In this review, we briefly summarise the functions
      of acute inflammation in muscle regeneration. The translational potential of this
      article: Immune system is closely relevant to the muscle regeneration.
      Understanding the mechanisms of inflammation in muscle regeneration is therefore
      critical for the development of effective regenerative, and therapeutic
      strategies in muscular disorders. This review provides information for muscle
      regeneration research regarding the effects of inflammation on muscle
      regeneration.

PMID- 29662790
TI  - Update on biomaterials for prevention of epidural adhesion after lumbar
      laminectomy.
AB  - Lumbar laminectomy often results in failed back surgery syndrome. Most scholars
      support the three-dimensional theory of adhesion: Fibrosis surrounding the
      epidural tissues is based on the injured sacrospinalis behind, fibrous rings and
      posterior longitudinal ligaments. Approaches including using the minimally
      invasive technique, drugs, biomaterial and nonbiomaterial barriers to prevent the
      postoperative epidural adhesion were intensively investigated. Nevertheless, the
      results are far from satisfactory. Our review is based on various implant
      biomaterials that are used in clinical applications or are under study. We show
      the advantages and disadvantages of each method. The summary will help us to
      figure out ideas towards new techniques. The translational potential of this
      article: This review summarises recent biomaterials-related clinical and basic
      research that focuses on prevention of epidural adhesion after lumbar
      laminectomy. We also propose a novel possible translational method where a soft
      scaffold acts as a physical barrier in the early stage, engineered adipose tissue
      acts as a biobarrier in the later stage in the application of biomaterials and
      adipose-derived mesenchymal stem cells are used for prevention of epidural
      adhesion.

PMID- 29662791
TI  - Meta-analysis of urinary C-terminal telopeptide of type II collagen as a
      biomarker in osteoarthritis diagnosis.
AB  - Objective: This study aims to discover that the urinary C-terminal telopeptide of
      type II collagen (uCTX-II) levels differ between osteoarthritis (OA) patients and
      healthy individuals (controls). According to this difference, we may conclude
      that uCTX-II can be a biomarker for OA diagnosis. Methods: We searched MEDLINE
      and EMBASE databases updated to 2014 to find literature on OA biomarkers. We
      retrieved the publications that met the required criterion. Literature quality
      was assessed according to the Newcastle-Ottawa Scale. Publication bias was
      assessed by Begg's test and Egger's test with the software STATA version 12.0.
      The weighted mean difference (WMD) was calculated, and the subgroup analysis was
      completed using STATA 12.0. Results: Six publications were included in our
      analysis. The WMD for OA patients versus the controls was 83.05, which was within
      the 95% confidence interval. For subgroup analysis, the WMD of patients with
      severe OA was 119.92, whereas that of patients with mild OA was 28.07.
      Conclusions: uCTX-II levels were higher in OA patients than in controls, subgroup
      analysis revealed that the uCTX-II levels rised with the OA severity, the
      heterogeneity originated from different levels of OA severity, These results
      showed that uCTX-II would be a promising clinical biomarker in OA diagnosis.

PMID- 29662792
TI  - Quantitative determination of residual 1,4-dioxane in three-dimensional printed
      bone scaffold.
AB  - Background/Objective: A novel porous scaffold poly (lactide-co-glycolide) and
      tricalcium phosphate (PLGA/TCP) was developed by three-dimensional printing
      technology for bone defect repair. As a Class 2 solvent with less severe
      toxicity, content of residual 1,4-dioxane in this newly developed scaffold should
      be rigorously controlled when it is translated to clinical use. In this study, a
      headspace gas chromatography-mass spectrometric (HS-GC-MS) method and related
      testing protocol were developed for quantitative determination of 1,4-dioxane in
      the PLGA/TCP composite scaffolds. Methods: Matrix effect analysis was used to
      optimise the pretreatment method of the scaffolds. Then, the procedure for
      testing 1,4-dioxane using HS-GC-MS was set up. The accuracy, precision, and
      robustness of this newly developed quantitative method were also validated before
      quantification of 1,4-dioxane in the scaffolds with different drying procedures.
      Results: Dimethyl formamide (DMF) was the optimal solvent for dissolving
      scaffolds for GC-MS with proper sensitivity and without matrix effect. Then, the
      optimised procedure was determined as: the scaffolds were dissolved in DMF and
      kept at 90 degrees C for 40 minutes, separated on a HP-5MS column, and detected
      by mass spectroscopy. Recovery experiments gave 97.9-100.7% recovery for 1,4
      dioxane. The linear range for 1,4-dioxane was determined as 1-40 ppm with linear
      correlation coefficient >= 0.9999. Intraday and interday precision was determined
      as being within relative standard deviation of below 0.68%. The passable drying
      procedure was related to lyophilising (-50 degrees C, 50 Pa) the scaffolds for 2
      days and drying in vacuum (50 Pa) for 7 days. Conclusion: This is the first
      quantitative method established to test 1,4-dixoane in a novel scaffold. This
      method was validated with good accuracy and reproducibility, and met the
      methodological requirements of the Guideline 9101 documented in the Chinese
      Pharmacopoeia 2015 Edition. The translational potential of this article: This
      quantitative method for determination of residual 1,4-dioxane in the novel
      scaffolds is a key technical method during its translation into clinical use
      because this method is an important and indispensable file in the enterprise
      standard when the porous scaffold is registered as a Class III implanted medical
      device for bone defect repair, which is used to guarantee the safety of the
      scaffolds. It is also applied to optimise the drying process of scaffolds and to
      monitor the quality of scaffolds in the industrialisation process. Further, this
      method provides references for other solvents quantitative determination in
      porous scaffolds or materials.

PMID- 29662793
TI  - Journal of Orthopaedic Translation now indexed in PubMed Central(c).

PMID- 29662794
TI  - Regenerative technologies to bed side: Evolving the regulatory framework.
AB  - There are high expectations for the clinical application of regenerative medicine
      technologies to treat musculoskeletal disorders. However, there are still big
      hurdles in bringing cell-based products to the market, mainly due to strict
      regulatory frameworks to approve these. Recently, the Japanese Pharmaceuticals
      and Medical Devices Agency adopted new regulations under legislature. The
      translational potential of this article is to inform on the regulations to bring
      experimental phase regenerative concepts to market approval in the United States
      and Europe, and highlight the opportunities granted by Japanese regulatory
      framework. Furthermore, we discuss the perspectives on the quickly evolving
      regulatory environment.

PMID- 29662795
TI  - Cell therapy for intervertebral disc repair: Clinical perspective.
AB  - Low back pain is the main cause of disability and is associated with
      intervertebral disc degeneration. Contemporary treatments are limited to
      palliative therapeutics or aggressive surgical interventions; however, current
      advancements in cell therapy offer to fill this breach. Clinical data suggest
      that cell transplantation can accomplish pain relief without any observed adverse
      effects. Despite a large variety of preclinical studies and preliminary clinical
      investigations, controversy remains on the optimal cell type and transplantation
      strategies. The translational potential of this article lies in the aim to update
      on the current state of intervertebral disc cell therapy and to identify current
      obstacles.

PMID- 29662796
TI  - Mesenchymal stem cells homing to improve bone healing.
AB  - Cell therapy continues to attract growing interest as a promising approach to
      treat a variety of diseases. Mesenchymal stem cells (MSCs) have been one of the
      most intensely studied candidates for cell therapy. Since the homing capacity of
      MSCs is an important determinant of effective MSC-based therapy, the enhancement
      of homing efficiency is essential for optimizing the therapeutic outcome.
      Furthermore, trafficking of endogenous MSCs to damaged tissues, also referred to
      as endogenic stem cell homing, and the subsequent participation of MSCs in tissue
      regeneration are considered to be a natural self-healing response. Therefore,
      strategies to stimulate and reinforce the mobilisation and homing of MSCs have
      become a key point in regenerative medicine. The current review focuses on
      advances in the mechanisms and factors governing trafficking of MSCs, and the
      relationship between MSC mobilisation and skeletal diseases, providing insights
      into strategies for their potential translational implications.

PMID- 29662797
TI  - Current concepts on tenogenic differentiation and clinical applications.
AB  - Tendon is a tissue that transmits force from muscle to bone. Chronic or acute
      tendon injuries are very common, and are always accompanied by pain and a limited
      range of motion in patients. In clinical settings, management of tendon injuries
      still remains a big challenge. Cell therapies, such as the application of stem
      cells for tenogenic differentiation, were suggested to be an ideal strategy for
      clinical translation. However, there is still a lack of specific methods for
      tenogenic differentiation due to the limited understanding of tendon biology
      currently. This review focuses on the summary of current published strategies for
      tenogenic differentiation, such as the application of growth factors, mechanical
      stimulation, biomaterials, coculture, or induced pluripotent stem cells. Current
      clinical applications of stem cells for treatment of tendon injuries and their
      limitations have also been discussed in this review.

PMID- 29662798
TI  - Intervertebral disc response to stem cell treatment is conditioned by disc state
      and cell carrier: An ex vivo study.
AB  - In vitro and in vivo studies evidenced that mesenchymal stem cells (MSCs)
      contribute to intervertebral disc (IVD) regeneration by differentiation towards
      the disc phenotype and matrix synthesis and/or by paracrine signalling to
      endogenous cells, thereby promoting a healthier disc phenotype in degenerative
      discs. The aim of this study was to investigate IVD response to human MSC (hMSC)
      treatment based on the disc degenerative state and hMSC carrier. Bovine caudal
      IVDs with endplates were cultured in a bioreactor under simulated physiological
      (0.1 Hz load and sufficient glucose) or degenerative (10 Hz load and limited
      glucose) conditions for 7 days. Discs were partially nucleotomised, restored with
      hMSCs in either fibrin gel or saline solution and cultured under physiological
      conditions for 7 days. Controls included fibrin and saline without hMSCs. Cell
      viability, histology, disc height, and gene expression analyses were performed to
      evaluate regeneration. hMSCs in fibrin were viable and homogenously distributed
      following 7 days of culture under dynamic loading in partially nucleotomised
      discs. IVD response to hMSCs was conditioned by both disc degenerative state and
      hMSC carrier. The effect of the regenerative treatment was stronger on simulated
      degenerative discs than on simulated-physiological discs. hMSCs in fibrin induced
      a superior anabolic response in degenerative IVDs compared with fibrin alone,
      thus suggesting an added value of the cellular therapy compared with an acellular
      solution. When comparing fibrin and saline as a hMSC carrier, a significantly
      higher anabolic response was observed in IVDs treated with hMSCs in fibrin.
      Moreover, it was found that the degenerative state of the disc influenced hMSC
      differentiation. Indeed, a significantly higher expression of specific discogenic
      markers (ACAN and CA12) was observed in hMSCs implanted into physiological discs
      than in those implanted into degenerative discs. In conclusion, host disc cells
      and donor hMSC response depend on the degenerative state of the host disc and
      carrier used for hMSC delivery, and these two aspects need to be considered for a
      successful translation of hMSC therapies for the treatment of IVD degeneration.

PMID- 29662799
TI  - Ultrasound as a stimulus for musculoskeletal disorders.
AB  - Ultrasound is an inaudible form of acoustic sound wave at 20 kHz or above that is
      widely used in the medical field with applications including medical imaging and
      therapeutic stimulation. In therapeutic ultrasound, low-intensity pulsed
      ultrasound (LIPUS) is the most widely used and studied form that generally uses
      acoustic waves at an intensity of 30 mW/cm2, with 200 ms pulses and 1.5 MHz. In
      orthopaedic applications, it is used as a biophysical stimulus for
      musculoskeletal tissue repair to enhance tissue regeneration. LIPUS has been
      shown to enhance fracture healing by shortening the time to heal and
      reestablishment of mechanical properties through enhancing different phases of
      the healing process, including the inflammatory phase, callus formation, and
      callus remodelling phase. Reports from in vitro studies reveal insights in the
      mechanism through which acoustic stimulations activate cell surface integrins
      that, in turn, activate various mechanical transduction pathways including FAK
      (focal adhesion kinase), ERK (extracellular signal-regulated kinase), PI3K, and
      Akt. It is then followed by the production of cyclooxygenase 2 and prostaglandin
      E2 to stimulate further downstream angiogenic, osteogenic, and chondrogenic
      cytokines, explaining the different enhancements observed in animal and clinical
      studies. Furthermore, LIPUS has also been shown to have remarkable effects on
      mesenchymal stem cells (MSCs) in musculoskeletal injuries and tissue
      regeneration. The recruitment of MSCs to injury sites by LIPUS requires the SDF-1
      (stromal cell derived factor-1)/CXCR-4 signalling axis. MSCs would then
      differentiate differently, and this is regulated by the presence of different
      cytokines, which determines their fates. Other musculoskeletal applications
      including bone-tendon junction healing, and distraction osteogenesis are also
      explored, and the results are promising. However, the use of LIPUS is
      controversial in treating osteoporosis, with negative findings in clinical
      settings, which may be attributable to the absence of an injury entry point for
      the acoustic signal to propagate, strong attenuation effect of cortical bone and
      the insufficient intensity for penetration, whereas in some animal studies it has
      proven effective.

PMID- 29662800
TI  - Pulsed electromagnetic field applications: A corporate perspective.
AB  - Corporate establishment of US Food & Drug Administration approved pulsed
      electromagnetic fields (PEMFs) for clinical applications has been achieved.
      However, optimization of PEMFs for improvement in efficacy for current
      indications, in addition to the expansion into new indications, is not trivial.
      Moving directly into a clinical trial can be costly and carries little guarantee
      for success, necessitating the need for preclinical studies as supported by this
      review of the extensive corporate preclinical experience by Orthofix, Inc. The
      Translational Potential of this Article: This review illustrates the need to gain
      enough in vitro/in vivo knowledge of specific PEMF signals and its target tissue
      interaction to enable a high success rate in clinical trials.

PMID- 29662801
TI  - Advances of stem cell based-therapeutic approaches for tendon repair.
AB  - Tendon injuries are significant clinical problems. Current treatments often
      result in incomplete repair or healing, which may lead to reduced function and
      rupture. Stem cell-based therapy is a promising intervention for tendon repair.
      In this article, we attempt to provide a brief overview on the recent progress in
      the field, current understanding of the underlying mechanisms of the approach,
      and the potential of stem cell-based therapies beyond cell implantation. We
      conclude the review by sharing our viewpoints on the challenges, opportunities,
      and future directions of this approach. The translational potential of this
      article: This paper reviews recent progress on stem cell-based therapeutic
      approaches for tendon repair, which highlights its translational potential and
      challenges.

PMID- 29662804
TI  - Stem cells and regenerative medicine: The time is right for translation.

PMID- 29662802
TI  - Cartilage repair by mesenchymal stem cells: Clinical trial update and
      perspectives.
AB  - Osteoarthritis is a degenerative disease of joints with destruction of articular
      cartilage associated with subchondral bone hypertrophy and inflammation. OA is
      the leading cause of joint pain resulting in significant worsening of the quality
      of-life in the elderly. Numerous efforts have been spent to overcome the
      inherently poor healing ability of articular cartilage. Mesenchymal stem cells
      (MSCs) have been in the limelight of cell-based therapies to promote cartilage
      repair. Despite progressive advancements in MSC manipulation and the introduction
      of various bioactive scaffolds and growth factors in preclinical studies, current
      clinical trials are still at early stages with preliminary aims to evaluate
      safety, feasibility and efficacy. This review summarises recently reported MSC
      based clinical trials and discusses new research directions with particular focus
      on the potential application of MSC-derived extracellular vehicles, miRNAs and
      advanced gene editing techniques which may shed light on the development of novel
      treatment strategies. The translational potential of this article: This review
      summarises recent MSC-related clinical research that focuses on cartilage repair.
      We also propose a novel possible translational direction for hyaline cartilage
      formation and a new paradigm making use of extra-cellular signalling and
      epigenetic regulation in the application of MSCs for cartilage repair.

PMID- 29662803
TI  - Role of mesenchymal stem cells in osteoarthritis treatment.
AB  - As the most common form of joint disorder, osteoarthritis (OA) imposes a
      tremendous burden on health care systems worldwide. Without effective cure, OA
      represents a unique opportunity for innovation in therapeutic development. In
      contrast to traditional treatments based on drugs, proteins, or antibodies, stem
      cells are poised to revolutionize medicine as they possess the capacity to
      replace and repair tissues and organs such as osteoarthritic joints. Among
      different types of stem cells, mesenchymal stem cells (MSCs) are of mesoderm
      origin and have been shown to generate cells for tissues of the mesoderm lineage,
      thus, raising the hope for them being used to treat diseases such as OA. However,
      given their ability to differentiate into other cell types, MSCs have also been
      tested in treating a myriad of conditions from diabetes to Parkinson's disease,
      apparently of the ectoderm and endoderm lineages. There are ongoing debates
      whether MSCs can differentiate into lineages outside of the mesoderm and
      consequently their effectiveness in treating conditions from the ectoderm and
      endoderm lineages. In this review, we discuss the developmental origin of MSCs,
      their differentiation potential and immunomodulatory effects, as well as their
      applications in treating OA. We suggest further investigations into new therapies
      or combination therapies that may provide more effective treatment for bone and
      joint diseases. Furthermore, cell-based therapy and its associated safety and
      effectiveness should be carefully evaluated before clinical translation. This
      review provides updated information on recent approval of clinical trials and
      related applications of MSCs, and discusses additional efforts on cell-based
      therapy for treating OA and other joint and bone diseases.

PMID- 29662805
TI  - Analysis of an Internet Community about Pneumothorax and the Importance of
      Accurate Information about the Disease.
AB  - Background: The huge improvements in the speed of data transmission and the
      increasing amount of data available as the Internet has expanded have made it
      easy to obtain information about any disease. Since pneumothorax frequently
      occurs in young adolescents, patients often search the Internet for information
      on pneumothorax. Methods: This study analyzed an Internet community for
      exchanging information on pneumothorax, with an emphasis on the importance of
      accurate information and doctors' role in providing such information. Results:
      This study assessed 599,178 visitors to the Internet community from June 2008 to
      April 2017. There was an average of 190 visitors, 2.2 posts, and 4.5 replies per
      day. A total of 6,513 posts were made, and 63.3% of them included questions about
      the disease. The visitors mostly searched for terms such as 'pneumothorax,'
      'recurrent pneumothorax,' 'pneumothorax operation,' and 'obtaining a medical
      certification of having been diagnosed with pneumothorax.' However, 22% of the
      pneumothorax-related posts by visitors contained inaccurate information.
      Conclusion: Internet communities can be an important source of information.
      However, incorrect information about a disease can be harmful for patients. We,
      as doctors, should try to provide more in-depth information about diseases to
      patients and to disseminate accurate information about diseases in Internet
      communities.

PMID- 29662806
TI  - Early Clinical Outcomes of Tricuspid Valve Repair with a Tri-Ad Annuloplasty Ring
      in Comparison with the Outcomes Using an MC3 Ring.
AB  - Background: We evaluated the early clinical outcomes of tricuspid valve
      annuloplasty (TAP) with the Tri-Ad annuloplasty ring for functional tricuspid
      regurgitation (TR). Methods: From January 2015 to March 2017, 36 patients
      underwent TAP with a Tri-Ad ring for functional TR. To evaluate the early
      clinical outcomes of TAP with the Tri-Ad ring, we conducted a propensity score
      matched analysis comparing the Tri-Ad and MC3 tricuspid annuloplasty rings (n=34
      in each group). The follow-up duration was 11.0+/-7.07 months. Results: There was
      1 case of operative mortality (2.8%) and no cases of late mortality.
      Postoperative complications occurred in 15 patients (41%), including acute kidney
      injury in 6 patients (16%), bleeding requiring reoperation in 4 patients (11%),
      and low cardiac output syndrome in 4 patients (11%). There were no ring-related
      complications, such as atrioventricular block or ring dehiscence. The TR grade
      decreased significantly (from 2.03+/-1.06 to 1.18+/-0.92, p<0.01), as did the
      systolic pulmonary artery pressure (from 43.53+/-13.84 to 38.00+/-9.72 mm Hg,
      p=0.03). There were no cases of severe residual TR, but moderate TR was observed
      in 3 patients, all of whom had severe TR preoperatively. Severe preoperative TR
      was also associated with moderate in the univariate analysis (p<0.01). In the
      propensity score-matched analysis comparing the Tri-Ad and MC3 rings, there was
      no significant difference in early clinical outcomes. Conclusion: TAP with the
      Tri-Ad ring corrected functional TR effectively and provided good early clinical
      and echocardiographic results without ring-related complications. However, severe
      preoperative TR was associated with moderate or severe residual TR in the
      immediate postoperative period. A follow-up study is necessary to confirm the
      stability of this procedure.

PMID- 29662808
TI  - Critical Illness-Related Corticosteroid Insufficiency in Patients with Low
      Cardiac Output Syndrome after Cardiac Surgery.
AB  - Background: Low cardiac output syndrome (LCOS) after cardiac surgery usually
      requires inotropes. In this setting, critical illness-related corticosteroid
      insufficiency (CIRCI) may develop. We aimed to investigate the clinical features
      of CIRCI in the presence of LCOS and to assess the efficacy of steroid treatment.
      Methods: We reviewed 28 patients who underwent a rapid adrenocorticotropic
      hormone (ACTH) test due to the suspicion of CIRCI between February 2010 and
      September 2014. CIRCI was diagnosed by a change in serum cortisol of <9 MUg/dL
      after the ACTH test or a random cortisol level of <10 MUg/dL. Results: Twenty of
      the 28 patients met the diagnostic criteria. The patients with CIRCI showed
      higher Sequential Organ Failure Assessment (SOFA) scores than those without CIRCI
      (16.1+/-2.3 vs. 11.4+/-3.5, p=0.001). Six of the patients with CIRCI (30%)
      received glucocorticoids. With an average elevation of the mean blood pressure by
      22.2+/-8.7 mm Hg after steroid therapy, the duration of inotropic support was
      shorter in the steroid group than in the non-steroid group (14.1+/-2.3 days
      versus 30+/-22.8 days, p=0.001). Three infections (15%) developed in the non
      steroid group, but this was not a significant between-group difference.
      Conclusion: CIRCI should be suspected in patients with LCOS after cardiac
      surgery, especially in patients with a high SOFA score. Glucocorticoid
      replacement therapy may be considered to reduce the use of inotropes without
      posing an additional risk of infection.

PMID- 29662807
TI  - Mechanical versus Tissue Aortic Prosthesis in Sexagenarians: Comparison of
      Hemodynamic and Clinical Outcomes.
AB  - Background: The question of which type of prosthetic aortic valve leads to the
      best outcomes in patients in their 60s remains controversial. We examined the
      hemodynamic and clinical outcomes of aortic valve replacement in sexagenarians
      according to the type of prosthesis. Methods: We retrospectively reviewed 270
      patients in their 60s who underwent first-time aortic valve replacement from 1995
      to 2011. Early and late mortality, major adverse valve-related events,
      anticoagulation-related events, and hemodynamic outcomes were assessed. The mean
      follow-up duration was 58.7+/-44.0 months. Results: Of the 270 patients, 93 had a
      mechanical prosthesis (mechanical group), and 177 had a bioprosthesis (tissue
      group). The tissue group had a higher mean age and prevalence of preoperative
      stroke than the mechanical group. The groups had no differences in the aortic
      valve mean pressure gradient (AVMPG) or the left ventricular mass index (LVMI) at
      5 years after surgery. In a sub-analysis limited to prostheses in the supra
      annular position, the AVMPG was higher in the tissue group, but the LVMI was
      still not significantly different. There was no early mortality. The 10-year
      survival rate was 83% in the mechanical group and 90% in the tissue group. The
      type of aortic prosthesis did not influence overall mortality, cardiac mortality,
      or major adverse valve-related events. Anticoagulation-related events were more
      common in the mechanical group than in the tissue group (p=0.034; hazard ratio,
      4.100; 95% confidence interval, 1.111-15.132). Conclusion: The type of aortic
      prosthesis was not associated with hemodynamic or clinical outcomes, except for
      anticoagulation-related events.

PMID- 29662809
TI  - Validation of Nafamostat Mesilate as an Anticoagulant in Extracorporeal Membrane
      Oxygenation: A Large-Animal Experiment.
AB  - Background: Unfractionated heparin is commonly used for anticoagulation in
      extracorporeal membrane oxygenation (ECMO). Several studies have shown that
      nafamostat mesilate (NM) has comparable clinical outcomes to unfractionated
      heparin. This study compared anticoagulation with NM and heparin in a large
      animal model. Methods: Beagle dogs (n=8; weight, 6.5-9 kg) were placed on
      venovenous ECMO. Blood samples were taken every hour and the following parameters
      were compared: hemoglobin level, activated partial thromboplastin time (aPTT),
      thromboelastography (TEG) data, platelet function, and inflammatory cytokine
      levels. Results: In both groups, the aPTT was longer than the baseline value.
      Although the aPTT in the NM group was shorter than in the heparin group, the TEG
      parameters were similar between the 2 groups. Hemoglobin levels decreased in both
      groups, but the decrease was less with NM than with heparin (p=0.049).
      Interleukin (IL)-1beta levels significantly decreased in the NM group (p=0.01),
      but there was no difference in the levels of tumor necrosis factor alpha or IL-10
      between the 2 groups. Conclusion: NM showed a similar anticoagulant effect to
      that of unfractionated heparin, with fewer bleeding complications. NM also had
      anti-inflammatory properties during ECMO. Based on this preclinical study, NM may
      be a good alternative candidate for anticoagulation in ECMO.

PMID- 29662810
TI  - Clinical Results of Arteriovenous Fistulas Constructed Using Autologous Vessels
      in End-Stage Renal Disease Patients on Hemodialysis.
AB  - Background: For hemodialysis patients with end-stage renal disease (ESRD), it is
      important to construct an efficient vascular access with a superior patency rate.
      This study investigated the factors influencing the efficiency of arteriovenous
      fistulas (AVFs) constructed using an autologous vessel and evaluated the
      necessity of ultrasonography as a preoperative tool for AVF construction.
      Methods: A retrospective analysis was performed of 250 patients in whom an AVF
      was constructed using an autologous vessel due to ESRD at our institution from
      January 2009 to April 2016. Results: The 1-, 3-, and 5-year patency rates for all
      subjects were 87.6%, 85.6%, and 84.4%, respectively. The patients who underwent a
      preoperative evaluation of their vessels via ultrasonography had better patency
      rates than those who did not. Superior patency rates were found in patients under
      65 years of age or with an anastomotic vein diameter of 3 mm or more. The 1-year
      patency rate and the diameter of the anastomotic vein showed a positive
      relationship. Conclusion: Ultrasonography is strongly recommended for AVF
      construction, and efforts should be made to increase the patency rate in patients
      over 65. Superior clinical results can be expected when an AVF is made using an
      autologous vessel with an anastomotic vein diameter of at least 3 mm.

PMID- 29662811
TI  - Management of Coronary Sinus Ostial Atresia during a Staged Operation of a
      Functional Single Ventricle.
AB  - Coronary sinus ostial atresia (CSOA) with persistent left superior vena cava
      (LSVC) in the absence of an unroofed coronary sinus is a benign and rare anomaly
      that may be taken lightly in most instances. However, if overlooked in patients
      undergoing univentricular heart repair such as bidirectional Glenn or Fontan-type
      surgery, fatal surgical outcomes may occur due to coronary venous drainage
      failure. We report a case of CSOA with a persistent LSVC that was managed through
      coronary sinus rerouting during a total cavopulmonary connection, and provide a
      review of the literature regarding this rare anomaly.

PMID- 29662812
TI  - Pulmonary Nodular Lymphoid Hyperplasia in a 33-Year-Old Woman.
AB  - Pulmonary nodular lymphoid hyperplasia is a reactive lymphoproliferative disease.
      It is very rare, which means that many aspects of the disease are unknown or have
      not been proven. Pulmonary nodular lymphoid hyperplasia can be symptomatic or
      asymptomatic, progressive or not, and solitary or multiple, and a surgical
      approach is the current treatment of choice. We present a case of pulmonary
      nodular lymphoid hyperplasia that was visualized as multiple ground glass
      opacities on a computed tomography (CT) scan, and observed for 1 year because the
      patient was pregnant. Over this period, the number and extent of the opacities
      progressed, but no symptoms were reported. A surgical biopsy was done and some
      remaining lesions regressed on follow-up CT scans, while others progressed,
      without any appearance of symptoms.

PMID- 29662813
TI  - Conjunction of a Fungus Ball and a Pulmonary Tumourlet in a Bronchiectatic
      Cavity.
AB  - Herein, we describe the case of a 67-year-old female patient who presented with
      cough and haemoptysis. Chest computed tomography revealed destruction of the left
      lower lobe and multiple fungus balls in a bronchiectatic cavity. A left lower
      lobectomy was performed via thoracotomy. Histopathological examination of the
      lung showed a concomitant aspergilloma and multiple tumourlets in the large
      bronchiectatic cavity. Pulmonary intracavitary aspergilloma and concomitant
      tumourlets are quite rare. Our report presents this interesting case that
      manifested with haemoptysis.

PMID- 29662814
TI  - Successful Surgical Treatment of a Recurrent Esophageal Malignant
      Gastrointestinal Neuroectodermal Tumor.
AB  - Malignant gastrointestinal neuroectodermal tumor (GNET) is a very rare disease
      entity, especially in the esophagus. The diagnosis of GNET is based on
      histologic, immunohistochemical, and genetic findings. The choice of treatment is
      complete resection, and further treatment options can be considered. Herein, we
      describe a case of successful surgical treatment of a 23-year-old man with
      recurrent malignant esophageal GNET.

PMID- 29662815
TI  - The Treatment of Left Atrial Appendage Aneurysm by a Minimally Invasive Approach.
AB  - Left atrial appendage (LAA) aneurysm is a rare, pathologic condition that may
      lead to atrial tachyarrhythmia or thromboembolic events. A 49-year-old man
      presented with aggravated palpitation and dizziness. He suffered from refractory
      atrial fibrillation despite a previous history of radiofrequency catheter
      ablation. Echocardiography revealed a 57-mm LAA aneurysm. Surgical ablation was
      performed through a right mini-thoracotomy, and the LAA aneurysm was obliterated
      with a 50-mm AtriClip (Atricure Inc., Westchester, OH, USA). However, follow-up
      computed tomography showed residual communication, so the patient is still taking
      warfarin. We report that a minimally invasive strategy for treating LAA aneurysm
      can be considered, but incomplete closure may occur; thus, caution is needed.

PMID- 29662816
TI  - Mitral Valve Replacement with a Pulmonary Autograft in an Infant.
AB  - A 76-day-old infant weighing 3.4 kg was referred for surgical intervention for
      severe mitral valve stenoinsufficiency caused by leaflet fibrosis and
      calcification. He had experienced a cerebral infarction in the left middle
      cerebral artery territory, which was deemed attributable to an embolism of a
      calcified particle from the dysmorphic mitral valve. Because mitral valve
      replacement using a prosthetic valve was not feasible in this small baby, mitral
      valve replacement with a pulmonary autograft was performed. After a brief period
      of extracorporeal membrane oxygenation (ECMO) support, he was weaned from ECMO
      and was discharged home without further cardiovascular complications.

PMID- 29662817
TI  - Concomitant Avulsion Injury of the Subclavian Vessels and the Main Bronchus
      Caused by Blunt Trauma.
AB  - Concomitant rupture of the subclavian vessels and the left main bronchus caused
      by blunt trauma is a serious condition. Moreover, the diagnosis of a
      tracheobronchial injury with rupture of the subclavian vessels can be difficult.
      This report describes the case of a 33-year-old man who suffered from blunt
      trauma that resulted in the rupture of the left subclavian artery and vein. The
      patient underwent an operation for vascular control. On postoperative day 3, the
      left main bronchus was found to be transected on a computed tomography scan and
      bronchoscopy. The transected bronchus was anastomosed in an end-to-end fashion.
      He recovered without any notable problems. Although the bronchial injury was not
      detected early, this case of concomitant rupture of the great vessels and the
      airway was successfully treated after applying extracorporeal membrane
      oxygenation.

PMID- 29662818
TI  - Cervicothoracic Thymic Cyst: An Unusual Presentation.
AB  - Cervicothoracic thymic cysts are rare and difficult to diagnose preoperatively.
      We report a case of a cervicothoracic thymic cyst presenting as a lateral neck
      mass and mimicking a laryngocele in a 3-year-old boy and its definitive
      management.

PMID- 29662819
TI  - Variable localization of Toll-like receptors in human fallopian tube epithelial
      cells.
AB  - Objective: To determine the localization, expression, and function of Toll-like
      receptors (TLRs) in fallopian tube epithelial cells. Methods: The localization of
      TLRs in fallopian tube epithelial cells was investigated by immunostaining.
      Surprisingly, the intensity of staining was not equal in the secretory and
      ciliated cells. After primary cell culture of fallopian tube epithelial cells,
      ring cloning was used to isolate colonies of ciliated epithelial cells, distinct
      from non-ciliated epithelial cells. The expression of TLRs 1-10 was examined by
      quantitative real-time polymerase chain reaction, and protein localization was
      confirmed by immunostaining. The function of the TLRs was determined by
      interleukin (IL)-6 and IL-8 production in response to TLR2, TLR3, TLR5, TLR7, and
      TLR9 ligands. Results: Fallopian tube epithelial cells expressed TLRs 1-10 in a
      cell-type-specific manner. Exposing fallopian tube epithelial cells to TLR2,
      TLR3, TLR5, TLR7, and TLR9 agonists induced the secretion of proinflammatory
      cytokines such as IL-6 and IL-8. Conclusion: Our findings suggest that TLR
      expression in the fallopian tubes is cell-type-specific. According to our
      results, ciliated cells may play more effective role than non-ciliated cells in
      the innate immune defense of the fallopian tubes, and in interactions with
      gametes and embryos.

PMID- 29662820
TI  - Effects of selenium on the survival and invasion of trophoblasts.
AB  - Objective: Placental oxidative stress is known to be a factor that contributes to
      pregnancy failure. The aim of this study was to determine whether selenium could
      induce antioxidant gene expression and regulate invasive activity and
      mitochondrial activity in trophoblasts, which are a major cell type of the
      placenta. Methods: To understand the effects of selenium on trophoblast cells
      exposed to hypoxia, the viability and invasive activity of trophoblasts were
      analyzed. The expression of antioxidant enzymes was assessed by reverse
      transcription polymerase chain reaction. In addition, the effects of selenium
      treatment on mitochondrial activity were evaluated in terms of adenosine
      triphosphate production, mitochondrial membrane potential, and reactive oxygen
      species levels. Results: Selenium showed positive effects on the viability and
      migration activity of trophoblast cells when exposed to hypoxia. Interestingly,
      the increased heme oxygenase 1 expression under hypoxic conditions was decreased
      by selenium treatment, whereas superoxide dismutase expression was increased in
      trophoblast cells by selenium treatment for 72 hours, regardless of hypoxia.
      Selenium-treated trophoblast cells showed increased mitochondrial membrane
      potential and decreased reactive oxygen species levels under hypoxic conditions
      for 72 hours. Conclusion: These results will be used as basic data for
      understanding the mechanism of how trophoblast cells respond to oxidative stress
      and how selenium promotes the upregulation of related genes and improves the
      survival rate and invasive ability of trophoblasts through regulating
      mitochondrial activity. These results suggest that selenium may be used in
      reproductive medicine for purposes including infertility treatment.

PMID- 29662821
TI  - Sperm chromatin and DNA integrity, methyltransferase mRNA levels, and global DNA
      methylation in oligoasthenoteratozoospermia.
AB  - Objective: To investigate sperm chromatin/DNA integrity, global DNA methylation,
      and DNMT mRNA transcription in men with oligoasthenoteratozoospermia (OAT)
      compared with normozoospermic men. Methods: Semen samples from 32 OAT patients
      who comprised the case group and 32 normozoospermic men who comprised the control
      group were isolated and purified using a standard gradient isolation procedure
      according to World Health Organization criteria. DNMT1, DNMT3A, and DNMT3B
      transcripts were then compared between groups using real-time quantitative
      reverse-transcription polymerase chain reaction. Global DNA methylation in sperm
      was determined by an enzyme-linked immunosorbent assay. Protamine deficiency and
      the proportion of apoptotic spermatozoa were evaluated using chromomycin A3
      (CMA3), aniline blue (AB), and toluidine blue (TB) staining, as well as the
      terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The p
      values <0.05 were considered to indicate statistical significance. Results:
      Significantly higher proportions of AB+, TB+, CMA3+, and TUNEL+ spermatozoa, as
      well as DNMT3A and DNMT3B transcription, were found in the OAT group. Positive
      correlations were detected between sperm parameters, DNA/chromatin damage, and
      DNMT3A and DNMT3B transcripts. Global DNA methylation was significantly higher in
      the OAT patients and had a significant correlation with abnormal results of all
      sperm chromatin integrity tests, but was not associated with DNMT1, DNMT3A, or
      DNMT3B expression. Conclusion: Oligoasthenoteratozoospermic men showed abnormal
      sperm parameters, abnormal chromatin/DNA integrity, and a higher global DNA
      methylation rate, as well as overexpression of DNMT mRNA.

PMID- 29662822
TI  - Effects of three-area laser-assisted zona thinning in 8-cell human embryos on
      pregnancy outcomes in vitro fertilization.
AB  - Objective: This study conducted a preliminary examination of the effects of three
      area laser-assisted zona thinning (LAZT) during the cleavage stage of embryo
      development on the hatching process in human in vitro fertilization-embryo
      transfer (IVF-ET) with subjects of advanced female age or frozen-thawed (FT)
      embryos. Methods: Eight-cell stage embryos were treated with LAZT in three areas
      of the zona pellucida at 120 degrees  intervals. The control group was embryos
      without LAZT. Of the 72 consecutive fresh cycles and the 28 FT embryo transfer
      cycles, the patients in 55 fresh cycles and 17 FT cycles declined LAZT, and those
      cycles were defined as the control group. Results: In the fresh cycles, the
      pregnancy rates were similar in the LAZT and control groups. However, in the FT
      cycles, the pregnancy rate was significantly higher in the LAZT group than in the
      control group (45.5% in the LAZT group vs. 23.5% in the control group, p<0.05).
      Conclusion: These results show that multi-area LAZT resulted in significantly
      improved pregnancy outcomes in human 8-cell embryos compared to controls.

PMID- 29662823
TI  - The likelihood of achieving pregnancy through timed coitus in young infertile
      women with decreased ovarian reserve.
AB  - Objective: To evaluate the pregnancy rate and time to pregnancy after timed
      coitus with or without superovulation in infertile young women younger than 35
      years old with low serum anti-Mullerian hormone (AMH) levels (<25th percentile).
      Methods: A total of 202 patients younger than 35 years old were recruited
      retrospectively between 2010 and 2012. Ninety-eight women had normal serum AMH
      levels (25-75th percentile), 75 women had low serum AMH levels (5th<=&<25th
      percentile) and 29 women had very low serum AMH levels (<5th percentile),
      according to reference values for their age group. Results: The clinical
      pregnancy rate was positively associated with AMH levels, but this trend did not
      reach statistical significance (43.9% vs. 41.3% vs. 27.6% in the normal, low, and
      very low AMH groups, respectively). The time to pregnancy was longer in the very
      low AMH group than in the normal AMH group (13.1+/-10.9 months vs. 6.9+/-6.1
      months, p=0.030). The cumulative live birth rate over 18 months was lower in the
      very low AMH group than in the normal AMH group, with marginal significance
      (20.0% vs. 55.9%, p=0.051). The duration of infertility was negatively correlated
      with achieving pregnancy (odds ratio, 0.953; 95% confidence interval, 0.914
      0.994; p=0.026). Conclusion: Conservative management, such as timed coitus with
      or without superovulation, should be considered in young patients who have low
      ovarian reserve without any infertility factors. However, for women with a long
      duration of infertility or very low serum AMH levels, active infertility
      treatment should be considered.

PMID- 29662824
TI  - Knowledge regarding factors that influence fertility in Thai reproductive-age
      population living in urban area: A cross-sectional study.
AB  - Objective: To survey knowledge about the factors that influence fertility in a
      reproductive-age population living in an urban area. Methods: A cross-sectional
      study was conducted using a questionnaire-based survey among both males and
      females aged 18-45 years living in the Bangkok metropolitan area. Results: The
      mean age of the participants was 26.8+/-7.2 years (male, 41.9%; female, 58.1%).
      Of the participants, 53.1% had an undergraduate degree and 57.1% were single.
      Only one-fifth of the participants correctly identified the age when fecundity
      declines in male and female, the definition of infertility, and the period during
      the menstrual cycle with the highest chance of pregnancy. Approximately three
      fourths of the participants correctly identified that cigarette smoking, alcohol
      consumption, and sexually transmitted infections affect fertility. Conclusion: A
      considerable knowledge gap about the factors that influence fertility was
      identified in reproductive-age individuals in an urban area of Thailand. This
      issue should be urgently addressed by promoting fertility awareness through
      education, discussions about social perceptions regarding fertility, and reliable
      sources of knowledge.

PMID- 29662825
TI  - Successful onco-testicular sperm extraction from a testicular cancer patient with
      a single testis and azoospermia.
AB  - Onco-testicular sperm extraction is used to preserve fertility in patients with
      bilateral testicular tumors and azoospermia. We report the case of a testicular
      tumor in the solitary testis of a patient who had previously undergone successful
      contralateral orchiectomy and whose sperm was preserved by onco-testicular sperm
      extraction. A 35-year-old patient presented with swelling of his right scrotum
      that had lasted for 1 month. His medical history included a contralateral
      orchiectomy during childhood. Ultrasonography revealed a mosaic echoic area in
      his scrotum, suggesting a testicular tumor. The lesion was palpated within the
      normal testicular tissue along its edge and semen analysis showed azoospermia.
      Radical inguinal orchiectomy and onco-testicular sperm extraction were performed
      simultaneously. Motile spermatozoa were extracted from normal seminiferous
      tubules under microscopy and were frozen. Eventual intracytoplasmic sperm
      injection using the frozen spermatozoa is planned. Onco-testicular sperm
      extraction is an important fertility preservation method in patients with
      bilateral testicular tumors or a history of a previous contralateral orchiectomy.

PMID- 29662826
TI  - An infertile patient with Y chromosome b1/b3 deletion presenting with congenital
      bilateral absence of the vas deferens with normal spermatogenesis.
AB  - We report the case of a 46-year-old Chinese male patient who visited our clinic
      complaining of infertility. Semen analysis revealed azoospermia, and azoospermia
      factor c region partial deletion (b1/b3) was detected using Y chromosome
      microdeletion analysis. Testicular sperm extraction was performed after genetic
      counseling. The bilateral ductus deferens and a portion of the epididymis were
      absent, whereas the remaining epididymis was expanded. Motile intratesticular
      spermatozoa were successfully extracted from the seminiferous tubule. On
      histopathology, nearly complete spermatogenesis was confirmed in almost every
      seminiferous tubule. To our knowledge, this is the first case report of b1/b3
      deletion with a congenital bilateral absence of the vas deferens and almost
      normal spermatogenesis.

PMID- 29662828
TI  - Acknowledgment to reviewers for 2017.

PMID- 29662827
TI  - Retrospective study of single vitrified-warmed blastocyst transfer cycles
      according to the presence of morphokinetic variables.
AB  - This study retrospectively assessed whether time-lapse data relating to
      developmental timing and morphology were associated with clinical outcomes, with
      the eventual goal of using morphokinetic variables to select embryos
      prospectively for cryopreservation. In this study, we examined the clinical
      outcomes of single vitrified-warmed blastocyst transfer cycles that were cultured
      in a time-lapse incubation system. The morphokinetic variables included uneven
      pronuclei, an uneven blastomere, multinucleation, and direct, rapid, and
      irregular division. A total of 164 single vitrified-warmed blastocyst transfer
      cycles were analyzed (102 cycles of regularly developed blastocysts and 62 cycles
      of blastocysts with morphokinetic variables). No significant differences in the
      age of females or the standard blastocyst morphology were found between these two
      groups. The regularly developed blastocysts showed significantly higher
      implantation and clinical pregnancy rates than the blastocysts exhibiting
      morphokinetic variables (30.4% vs. 9.7% and 37.3% vs. 14.5%, respectively;
      p<0.01). The blastocysts that exhibited morphokinetic variables showed different
      mean development times compared with the regularly developed blastocysts.
      Although morphokinetic variables are known to have fatal impacts on embryonic
      development, a considerable number of embryos developed to the blastocyst stage.
      Morphokinetic variables had negative effects on the implantation and clinical
      pregnancy rates in vitrified-warmed blastocyst transfer cycles. These findings
      suggest that blastocysts cultured in a time-lapse incubation system should be
      considered for selective cryopreservation according to morphokinetic variables.

PMID- 29662829
TI  - Lenvatinib May Drastically Change the Treatment Landscape of Hepatocellular
      Carcinoma.

PMID- 29662830
TI  - Combination Cancer Immunotherapy in Hepatocellular Carcinoma.

PMID- 29662831
TI  - The Asia Pacific Consensus Statement on Laparoscopic Liver Resection for
      Hepatocellular Carcinoma: A Report from the 7th Asia-Pacific Primary Liver Cancer
      Expert Meeting Held in Hong Kong.
AB  - Background: Laparoscopic liver resection has been gaining momentum, and it has
      become an accepted practice after the two international consensus conferences
      where experts worked up guidelines to standardize this approach and improve its
      safety. However, most laparoscopic hepatectomies were performed in patients with
      liver metastases. The concurrent presence of liver cirrhosis with hepatocellular
      carcinoma (HCC) poses a great challenge to clinicians trying to establish a
      routine use of laparoscopic liver resection for HCC. Summary: The first Asia
      Pacific consensus meeting on laparoscopic liver resection for HCC was held in
      July 2016 in Hong Kong. A group of expert liver surgeons with experience in both
      open and laparoscopic hepatectomy for HCC convened to formulate recommendations
      on the role and perspective of laparoscopic liver resection for primary liver
      cancer. The recommendations consolidate the most recent evidence pertaining to
      laparoscopic hepatectomy together with the latest thinking of practicing
      clinicians involved in laparoscopic hepatectomy, and give detailed guidance on
      how to deploy the treatment effectively for patients in need. Key Message: The
      panel of experts gathered evidence and produced recommendations providing
      guidance on the safe practice of laparoscopic hepatectomy for patients with HCC
      and cirrhosis. The inherent advantage of the laparoscopic approach may result in
      less blood loss if the procedure is performed in experienced centers. The
      laparoscopic approach to minor hepatectomy, particularly left lateral
      sectionectomy, is a preferred practice for HCC at experienced centers.
      Laparoscopic major liver resection for HCC remains a technically challenging
      operation, and it should be carried out in centers of excellence. There is
      emerging evidence that laparoscopic liver resection produces a better oncological
      outcome for HCC when compared with radiofrequency ablation, particularly when the
      lesions are peripherally located. Augmented features in laparoscopic liver
      resection, including indocyanine green fluorescence, 3D laparoscopy, and robot,
      will become important tools of surgical treatment in the near future. A
      combination of all of these features will enhance the experience of the surgeons,
      which may translate into better surgical outcomes. This is the first consensus
      workforce on laparoscopic liver resection for HCC, which is a unique condition
      that occurs in the Asia Pacific region.

PMID- 29662832
TI  - Hong Kong Consensus Statements for the Management of Unresectable Hepatocellular
      Carcinoma.
AB  - Background: Hepatocellular carcinoma (HCC) is highly prevalent in Hong Kong due
      to the high prevalence of chronic hepatitis B infection. Liver cancer is the
      fourth most common cancer and the third most common cause of cancer death. Due to
      the high case load, there is a high level of local expertise in treating HCC, and
      the full spectrum of treatment modalities is available. This document summarizes
      how these modalities should be used based on the latest evidence. Summary: In 2
      meetings held in early 2017, a multidisciplinary group of Hong Kong clinicians,
      including liver surgeons, interventional radiologists, clinical oncologists, and
      medical oncologists, met to update local consensus statements for management of
      HCC. These statements are based on the latest evidence and give detailed guidance
      on how to deploy these modalities, in particular for cases of HCC which are not
      suited to surgical resection. Key Messages: These statements give detailed
      information on how to decide if a patient is a candidate for resection, methods
      to improve candidacy for resection, and guidance for use of various nonsurgical
      interventions to manage patients ineligible for resection.

PMID- 29662833
TI  - Short-Term Outcomes following Hepatectomy in Elderly Patients with Hepatocellular
      Carcinoma: An Analysis of 10,805 Septuagenarians and 2,381 Octo- and
      Nonagenarians in Japan.
AB  - Background: As the population is aging, the indication for hepatocellular
      carcinoma (HCC) resection in patients aged over 80 years will increase. Japan is
      facing the most aging society worldwide. We examined the safety of hepatectomy in
      octogenarians and nonagenarians using large-scale data from the Diagnosis
      Procedure Combination database, a national administrative database in Japan.
      Method: We conducted a survey to collect data for all inpatients from 2007 and
      2012. We identified 27,094 patients who underwent hepatectomy for HCC. Patients'
      age was divided into the following five categories: <=59, 60-69, 70-79, 80-84,
      and >=85 years (n = 5,099, 8,809, 10,805, 2,011, and 370, respectively). The
      primary outcomes of hepatectomy were in-hospital death within 90 days and
      complications. Logistic regression analyses were performed to analyze the impact
      of age on the outcomes with the adjustment of other individual-level factors.
      Results: The mortality and morbidity rates were 2.6 and 23.4%, respectively.
      Compared with patients in their 70s, the mortality rate was significantly lower
      in patients aged <=59 years (odds ratio [OR], 0.34; 95% confidence interval [CI],
      0.26-0.45; p < 0.01) and in those in their 60s (OR, 0.63; 95% CI, 0.53-0.74; p <
      0.01). However, no significant difference was observed in patients aged 80-84
      years (OR, 1.03; 95% CI, 0.78-1.385; p = 0.844) and those aged >=85 years (OR,
      0.95; 95% CI, 0.50-1.79; p = 0.870). Based on the multivariate logistic
      regression analysis, age >=70 years, male gender, low hospital volume, and
      surgical procedure were identified as independent predictors of mortality.
      Conclusions: The operative risk for hepatectomy gradually increases with age
      until patients are in their 70s, and it appears to reach a plateau among
      septuagenarian. Indeed, age over 70 years can also be a risk factor for HCC. By
      considering the aging risk, surgeons can attain good outcome after hepatectomy
      even in octo- and nonagenarian patients.

PMID- 29662834
TI  - Liver Stiffness Measured by Two-Dimensional Shear-Wave Elastography: Prognostic
      Value after Radiofrequency Ablation for Hepatocellular Carcinoma.
AB  - Purpose: To evaluate the prognostic value of liver stiffness (LS) measured using
      two-dimensional (2D) shear-wave elastography (SWE) in patients with
      hepatocellular carcinoma (HCC) treated by radiofrequency ablation (RFA). Methods:
      The Institutional Review Board approved this retrospective study and informed
      consent was obtained from all patients. A total of 134 patients with up to 3 HCCs
      <=5 cm who had undergone pre-procedural 2D-SWE prior to RFA treatment between
      January 2012 and December 2013 were enrolled. LS values were measured using real
      time 2D-SWE before RFA on the procedural day. After a mean follow-up of 33.8 +/-
      9.9 months, we analyzed the overall survival after RFA using the Kaplan-Meier
      method and Cox proportional hazard regression model. The optimal cutoff LS value
      to predict overall survival was determined using the minimal p value approach.
      Results: During the follow-up period, 22 patients died, and the estimated 1- and
      3-year overall survival rates were 96.4 and 85.8%, respectively. LS measured by
      2D-SWE was found to be a significant predictive factor for overall survival after
      RFA of HCCs, as was the presence of extrahepatic metastases. As for the optimal
      cutoff LS value for the prediction of overall survival, it was determined to be
      13.3 kPa. In our study, 71 patients had LS values >=13.3 kPa, and the estimated 3
      year overall survival was 76.8% compared to 96.3% in 63 patients with LS values
      <13.3 kPa. This difference was statistically significant (hazard ratio = 4.30
      [1.26-14.7]; p = 0.020). Conclusion: LS values measured by 2D-SWE was a
      significant predictive factor for overall survival after RFA for HCC.

PMID- 29662835
TI  - Preoperative Low Muscle Mass and Low Muscle Quality Negatively Impact on
      Pulmonary Function in Patients Undergoing Hepatectomy for Hepatocellular
      Carcinoma.
AB  - Background: Sarcopenia is a prognostic factor for mortality in digestive surgery.
      However, the correlation between preoperative cardiopulmonary function and
      sarcopenia in patients undergoing hepatectomy for hepatocellular carcinoma (HCC)
      remains unclear. Methods: The present study investigated the impact of
      preoperative sarcopenia on cardiopulmonary function in 402 patients who underwent
      first hepatectomy for HCC between April 2005 and April 2015. The quantity and
      quality of skeletal muscle were evaluated using psoas muscle index (PMI) and
      intramuscular adipose tissue content (IMAC), respectively, as determined from
      preoperative computed tomography imaging. Correlations between preoperative
      cardiopulmonary function and sarcopenic factors (PMI and IMAC) were evaluated.
      Results: No significant correlations were found between left ventricular ejection
      fraction and the two sarcopenic factors. On the other hand, preoperative vital
      capacity (VC) and forced expiratory volume in 1 s (FEV1) correlated significantly
      with PMI (p < 0.001 each) in males and with IMAC (p < 0.001 each) in females.
      Moreover, VC and FEV1 in the preoperative low PMI (p < 0.001 each) and high IMAC
      (p = 0.002 and p < 0.001, respectively) groups were significantly lower than in
      the normal group in males. In females, VC and FEV1 were significantly lower in
      the preoperative high IMAC group than in the normal group (p < 0.001 each).
      Conclusion: Preoperative low muscle mass in males and low muscle quality in males
      and females were significantly associated with pulmonary dysfunction.

PMID- 29662836
TI  - Association between Loss of Skeletal Muscle Mass and Mortality and Tumor
      Recurrence in Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.
AB  - Background: Hepatocellular carcinoma (HCC) has multiple prognostic factors, and
      there is an increase in knowledge about the body composition and physical status
      of patients with HCC. The present meta-analysis aimed to explore whether loss of
      skeletal muscle mass is associated with mortality and tumor recurrence in
      patients with HCC. Method: A systematic search was conducted for published
      literature using PubMed, Embase, and Scopus. We included cohort or case-control
      studies investigating patients with HCC. The primary and secondary outcomes were
      the associations of loss of skeletal muscle mass with overall survival and tumor
      recurrence, respectively, expressed by a summary hazard ratio (HR) and 95%
      confidence interval (CI). Result: A total of 13 studies comprising 3,111 patients
      were included. The summary HRs calculated by either univariate or multivariate
      analysis both suggested a significant association between sarcopenia and all
      cause mortality (crude HR = 2.04, 95% CI: 1.74-2.38; adjusted HR = 1.95, 95% CI:
      1.60-2.37). Similarly, loss of skeletal muscle mass was associated with tumor
      recurrence (crude HR = 1.85, 95% CI: 1.44-2.37; adjusted HR = 1.76, 95% CI: 1.27
      2.45). The stratified analysis showed that treatment types and inclusion of body
      mass index or body weight in the Cox regression model did not modify both
      clinical outcomes. With an increase in cut-off values of muscle mass on computed
      tomography images (especially for male patients), there was an insignificant
      trend of stronger associations between loss of skeletal muscle mass and all-cause
      mortality. Conclusion: Loss of skeletal muscle mass is associated with increased
      all-cause mortality and tumor recurrence in patients with HCC. Further
      prospective studies incorporating measurements of muscle strength and physical
      function are warranted to see whether inclusion of both parameters better
      predicts the outcome than use of muscle mass only.

PMID- 29662837
TI  - Patient Selection for Transarterial Chemoembolization in Hepatocellular
      Carcinoma: Importance of Benefit/Risk Assessment.
AB  - Background: Liver cancer is the second most common cause of cancer-related death,
      with hepatocellular carcinoma (HCC) accounting for most primary liver cancers and
      most commonly arising from a history of advanced chronic liver disease. Among the
      available therapies, transarterial chemoembolization (TACE) is the most widely
      utilized and is considered the first-line treatment recommended for patients
      staged as intermediate HCC (Barcelona Clinic Liver Cancer stage B). If applied
      correctly, TACE can produce survival benefits without adversely affecting hepatic
      functional reserve. Summary: The aim of this nonsystematic review is to evaluate
      the evidence supporting TACE, with a special interest in intermediate HCC, for
      which this treatment is recommended in first line. However, intermediate HCC
      represents a broad and heterogeneous group of patients, not all of whom will
      benefit from TACE. This review highlights the importance of appropriate patient
      selection for initial TACE and for retreatment. It also evaluates evidence for
      the treatment of patients who become refractory to TACE. Some patients may, in
      fact, benefit from early switch (i.e., after 1 or 2 TACE treatments) to systemic
      therapies rather than continuing retreatments with TACE in order to preserve
      liver function, thus allowing sequential first- and second-line drug therapies.
      Key Messages: Careful assessment of an individual patient's benefit/risk ratio is
      recommended before any TACE session is considered to ensure optimal long-term
      outcomes in intermediate HCC.

PMID- 29662838
TI  - The CpxA/CpxR Two-Component System Affects Biofilm Formation and Virulence in
      Actinobacillus pleuropneumoniae.
AB  - Gram-negative bacteria have evolved numerous two-component systems (TCSs) to cope
      with external environmental changes. The CpxA/CpxR TCS consisting of the kinase
      CpxA and the regulator CpxR, is known to be involved in the biofilm formation and
      virulence of Escherichia coli. However, the role of CpxA/CpxR remained unclear in
      Actinobacillus pleuropneumoniae, a bacterial pathogen that can cause porcine
      contagious pleuropneumonia (PCP). In this report, we show that CpxA/CpxR
      contributes to the biofilm formation ability of A. pleuropneumoniae. Furthermore,
      we demonstrate that CpxA/CpxR plays an important role in the expression of
      several biofilm-related genes in A. pleuropneumoniae, such as rpoE and pgaC.
      Furthermore, The results of electrophoretic mobility shift assays (EMSAs) and
      DNase I footprinting analysis demonstrate that CpxR-P can regulate the expression
      of the pgaABCD operon through rpoE. In an experimental infection of mice, the
      animals infected with a cpxA/cpxR mutant exhibited delayed mortality and lower
      bacterial loads in the lung than those infected with the wildtype bacteria. In
      conclusion, these results indicate that the CpxA/CpxR TCS plays a contributing
      role in the biofilm formation and virulence of A. pleuropneumoniae.

PMID- 29662839
TI  - The Saposin-Like Protein AplD Displays Pore-Forming Activity and Participates in
      Defense Against Bacterial Infection During a Multicellular Stage of Dictyostelium
      discoideum.
AB  - Due to their archaic life style and microbivor behavior, amoebae may represent a
      source of antimicrobial peptides and proteins. The amoebic protozoon
      Dictyostelium discoideum has been a model organism in cell biology for decades
      and has recently also been used for research on host-pathogen interactions and
      the evolution of innate immunity. In the genome of D. discoideum, genes can be
      identified that potentially allow the synthesis of a variety of antimicrobial
      proteins. However, at the protein level only very few antimicrobial proteins have
      been characterized that may interact directly with bacteria and help in fighting
      infection of D. discoideum with potential pathogens. Here, we focus on a large
      group of gene products that structurally belong to the saposin-like protein
      (SAPLIP) family and which members we named provisionally Apls (amoebapore-like
      peptides) according to their similarity to a comprehensively studied
      antimicrobial and cytotoxic pore-forming protein of the protozoan parasite
      Entamoeba histolytica. We focused on AplD because it is the only Apl gene that is
      reported to be primarily transcribed further during the multicellular stages such
      as the mobile slug stage. Upon knock-out (KO) of the gene, aplD- slugs became
      highly vulnerable to virulent Klebsiella pneumoniae. AplD- slugs harbored
      bacterial clumps in their interior and were unable to slough off the pathogen in
      their slime sheath. Re-expression of AplD in aplD- slugs rescued the
      susceptibility toward K. pneumoniae. The purified recombinant protein rAplD
      formed pores in liposomes and was also capable of permeabilizing the membrane of
      live Bacillus megaterium. We propose that the multifarious Apl family of D.
      discoideum comprises antimicrobial effector polypeptides that are instrumental to
      interact with bacteria and their phospholipid membranes. The variety of its
      members would allow a complementary and synergistic action against a variety of
      microbes, which the amoeba encounters in its environment.

PMID- 29662840
TI  - Activation of the NLRP3 Inflammasome Pathway by Uropathogenic Escherichia coli Is
      Virulence Factor-Dependent and Influences Colonization of Bladder Epithelial
      Cells.
AB  - The NLRP3 inflammasome and IL-1beta release have recently been suggested to be
      important for the progression of urinary tract infection (UTI). However, much is
      still unknown regarding the interaction of UPEC and the NLRP3 inflammasome. The
      purpose of this study was to elucidate what virulence factors uropathogenic
      Escherichia coli (UPEC) use to modulate NLRP3 inflammasome activation and
      subsequent IL-1beta release and the role of NLRP3 for UPEC colonization of
      bladder epithelial cells. The bladder epithelial cell line 5637, CRISPR/Cas9
      generated NLRP3, caspase-1 and mesotrypsin deficient cell lines and transformed
      primary bladder epithelial cells (HBLAK) were stimulated with UPEC isolates and
      the non-pathogenic MG1655 strain. We found that the UPEC strain CFT073, but not
      MG1655, induced an increased caspase-1 activity and IL-1beta release from bladder
      epithelial cells. The increase was shown to be mediated by alpha-hemolysin
      activation of the NLRP3 inflammasome in an NF-kappaB-independent manner. The
      effect of alpha-hemolysin on IL-1beta release was biphasic, initially
      suppressive, later inductive. Furthermore, the phase-locked type-1-fimbrial ON
      variant of CFT073 inhibited caspase-1 activation and IL-1beta release. In
      addition, the ability of CFT073 to adhere to and invade NLRP3 deficient cells was
      significantly reduced compare to wild-type cells. The reduced colonization of
      NLRP3-deficient cells was type-1 fimbriae dependent. In conclusion, we found that
      the NLRP3 inflammasome was important for type-1 fimbriae-dependent colonization
      of bladder epithelial cells and that both type-1 fimbriae and alpha-hemolysin can
      modulate the activity of the NLRP3 inflammasome.

PMID- 29662841
TI  - Effect of Mixed Fruit and Vegetable Juice on Alcohol Hangovers in Healthy Adults.
AB  - The purpose of this study was to investigate the effects of mixed fruit and
      vegetable juice on alcohol hangover in healthy adults in a randomized crossover
      trial. Angelica keiskei/green grape/pear juice (AGP juice) was a mixture of A.
      keiskei juice, green grape juice, and pear juice at 1:1:1 ratio. Alcohol
      dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activities of AGP juice
      were measured in vitro. Fifteen healthy adults consumed alcohol (1.25 g/kg
      weight), and either water (control group) or AGP juice (AGP juice group). Blood
      was collected and expiratory-air alcohol levels were measured at 0~360 min after
      drinking the alcohol. Compared with control, AGP juice had higher ADH and ALDH
      activity in vitro. The peak alcohol levels in expiratory-air and plasma after
      drinking AGP juice were significantly lower than those after drinking water. The
      area under the curves for expiratory-air and plasma alcohol of the AGP juice
      group were lower than those of the control group. Thirst and headache scores
      after intake of alcohol were significantly reduced by AGP juice consumption
      compared with the control group. These data demonstrated that AGP juice could
      contribute to eliminate alcohol toxicity and hangover symptoms by enhancing
      alcohol metabolizing enzyme activities.

PMID- 29662842
TI  - Antioxidative and Cholesterol-Lowering Effects of Lemon Essential Oil in
      Hypercholesterolemia-Induced Rabbits.
AB  - The cholesterol-lowering and anti-atherogenic effects of lemon essential oil
      (LEO) were investigated and compared with the effects of limonene. Owing to their
      volatility, both LEO and limonene were microencapsulated before preparation of
      the diet (20%, w/w). Hypercholesterolemia-induced rabbits were divided into 3
      groups based on plasma total cholesterol (TC) levels and fed coating matrix
      (control group), LEO (LEO group), or limonene (Limonene group) for 8 weeks. LEO
      dose-dependently inhibited low-density lipoprotein oxidation in vitro. Plasma TC
      levels were the lowest in the LEO group (P<0.05). Erythrocytes in the LEO group
      had a normal disc shape, whereas the erythrocytes in the limonene and control
      groups were aggregated and star-shaped, respectively. The aortic intima thickness
      was thinnest in the LEO group followed by the control and limonene groups. Plasma
      TC lowering and anti-atherogenic effects of LEO were greater than limonene,
      suggesting that other bioactive compounds besides limonene in LEO might
      contribute to these effects. The bioactive compounds in LEO were limonene
      (67.57%), beta-pinene (10.00%), and gamma-terpinene (9.95%). In addition,
      sabinene, alpha-pinene, myrcene, and geranial were also present but the amount
      was in the range of 1~2%. Several bioactive compounds were also detected. In
      conclusion, LEO had beneficial effects on hypercholesterolemia due to its
      antioxidative and cholesterol lowering effects.

PMID- 29662843
TI  - Insulinotropic Effect of S-Allyl Cysteine in Rat Pups.
AB  - S-Allyl cysteine (SAC) is found in garlic and has been reported to exert
      antidiabetic and antiobesity properties in drug-induced adult experimental models
      of metabolic dysfunction, but its potential beneficial effects in high-fructose
      diet neonatal rat models have not been determined. This study investigated the
      potential prophylactic effects of SAC in high-fructose diet fed suckling rat pups
      modelling human neonates fed a high-fructose diet. Four-day-old male (n=32) and
      female (n=32) Wistar rat pups, were randomly assigned to and administered the
      following treatment regimens daily for 15 days: group I, distilled water; group
      II, 20% fructose solution (FS); group III, SAC; group IV, SAC+FS. The pups' blood
      glucose, triglyceride, cholesterol, plasma leptin and insulin concentration,
      liver lipid content, and liver histology were determined at termination. In
      female rat pups, orally administered SAC prevented FS-induced hypoinsulinemia but
      significantly increased (P<=0.05) liver lipid content. Oral administration of SAC
      significantly increased (P<=0.05) plasma insulin concentration and homeostasis
      model assessment for insulin resistance in the male pups. The potential sexually
      dimorphic effects of SAC (insulinotropic effects in male pups and protection of
      female pups against fructose-induced hypoinsulinemia) suggest that SAC could be
      potentially exploited as an antidiabetic and insulinotropic agent. Caution
      should, however, be exercised in the use of SAC during suckling as it could
      result in excessive liver lipid accumulation and insulin resistance.

PMID- 29662844
TI  - Mineral Elements Bio-Accessibility and Antioxidant Indices of Blanched Basella
      rubra at Different Phases of in vitro Gastrointestinal Digestion.
AB  - The present investigation was designed to evaluate the mineral element bio
      accessibility and antioxidant indices of blanched Basella rubra at different
      phases of simulated in vitro digestion (oral, gastric, and intestinal). The
      phenolic composition of processed vegetable was determined using high-performance
      liquid chromatography (HPLC)-diode-array detection method. Mineral composition,
      total phenolic content (TPC), total flavonoid content (TFC), ferric reducing
      antioxidant power (FRAP), and total antioxidant activity (TAA) of the in vitro
      digested blanched and raw vegetable were also determined. HPLC analysis revealed
      the presence of some phenolic compounds, with higher levels (mg/g) of polyphenols
      in raw B. rubra (catechin, 1.12; p-coumaric acid, 6.17; caffeic acid, 2.05)
      compared with the blanched counterpart, with exeption of chlorogenic acid (2.84),
      that was higher in blanched vegetable. The mineral content (mg/100 g) showed a
      higher value in enzyme treated raw vegetable compared to their blanched
      counterparts, with few exceptions. The results revealed a higher level of some of
      the evaluated minerals at the intestinal phase of digestion (Zn, 6.36/5.31; Mg,
      5.29/8.97; Ca, 2,307.69/1,565.38; Na, 5,128/4,128.21) for raw and blanched
      respectively, with the exception of Fe, K, and P. The results of the antioxidant
      indices of in vitro digested B. rubra revealed a higher value at the intestinal
      phase of in vitro digestion, with raw vegetal matter ranking higher (TPC, 553.56
      mg/g; TFC, 518.88 mg/g; FRAP, 8.15 mg/g; TAA, 5,043.16 MUM Trolox equivalent/g)
      than the blanched counterpart. The studied vegetable contains important minerals
      and antioxidant molecules that would be readily available after passing through
      the gastrointestinal tract and could be harnessed as functional foods.

PMID- 29662845
TI  - Suppressive Effects of Vaccinium angustifolium Root Extract via Down-Regulation
      of Activation of Syk, Lyn, and NF-kappaB in FcERI-Mediated Allergic Reactions.
AB  - Vaccinium angustifolium, reported as the lowbush blueberry, has a rich
      polyphenolic content with which biological activities have been closely
      associated. In this study, the effects of V. angustifolium root extract (VAE) on
      the anti-FcERI alpha chain antibody (CRA-1)-induced FcERI-mediated signaling
      factors, protein tyrosine kinases (PTK), Lyn, Syk, and nuclear factor kappa-B
      cells (NF-kappaB) in KU812F cells were investigated. The total phenolic content
      of VAE was found to be 170+/-1.9 mg gallic acid equivalents/g. Western blot
      analysis revealed that VAE dose-dependently inhibited FcERI-mediated
      phosphorylation of PTK involving Lyn and Syk. Evaluation of intracellular
      reactive oxygen species (ROS) by spectrofluorometric analysis using 2'7'
      dichlorofluorescin-diacetate revealed that they were reduced by VAE in a dose
      dependent manner. Moreover, VAE reduced the levels of beta-hexosaminidase
      released from CRA-1-stimulated KU812F cells. It was identified that VAE
      suppressed CRA-1-induced activation of NF-kappaB by Western blot analysis. Our
      results show that VAE may contribute to the inhibition of allergic actions via
      inactivation of basophils through the inhibition of beta-hexosaminidase release
      and ROS production, which occurs as a result of inhibition of PTK, Syk, Lyn, and
      NF-kappaB.

PMID- 29662846
TI  - Antioxidant Activities of Selected Berries and Their Free, Esterified, and
      Insoluble-Bound Phenolic Acid Contents.
AB  - To explore the potential of berries as natural sources of bioactive compounds,
      the quantities of free, esterified, and insoluble-bound phenolic acids in a
      number of berries were determined. In addition, the antioxidant activities of the
      berries were determined using 2,2-diphenyl-1-picrylhydrazyl radical scavenging
      activity, ferric reducing antioxidant power, and Trolox equivalent antioxidant
      capacity assays, in addition to determination of their metal ion chelating
      activities. Furthermore, several phenolic compounds were detected using high
      performance liquid chromatography. Of the 6 tested berries, black chokeberry and
      blackberry exhibited the strongest antioxidant activities, and the various berry
      samples were found to contain catechin, caffeic acid, p-coumaric acid,
      epicatechin, vanillic acid, quercitrin, resveratrol, morin, naringenin, and
      apigenin. Moreover, the antioxidant activities and total phenolic contents of the
      fractions containing insoluble-bound phenolic acids were higher than those
      containing the free and esterified phenolic acids. The results imply that the
      insoluble-bound fractions of these berries are important natural sources of
      antioxidants for the preparation of functional food ingredients and preventing
      diseases associated with oxidative stress.

PMID- 29662847
TI  - Impact of Various Factors on Color Stability of Fresh Blueberry Juice during
      Storage.
AB  - The attractive purple color of blueberries (Vaccinium spp.) is unstable and
      susceptible to degradation during food processing and storage. The effects of
      various factors on the color stability of fresh blueberry juice were
      investigated. Total soluble solid content, pH, and total anthocyanin content were
      measured. Heating at 30 degrees C and 60 degrees C for 300 min did not influence
      the color stability, but heating at 100 degrees C drastically decreased it by
      33.0%. Sugars decreased color in a concentration-dependent manner. However,
      glucose and galactose had significantly protective effects on the color
      disruption than fructose, maltose, and sucrose. Organic acids lowered the color
      intensity in the order of citric acid> tartaric acid> malic acid> formic acid>
      acetic acid during 10 days of storage. Color decreased faster during long-term
      light exposure than in the dark. The color in the dark was kept by 58.7% after 7
      weeks, while 48.9% in the light. Color retention was significantly decreased to
      93.5% and 93.8% at 4 degrees C and -20 degrees C, respectively, after 7 weeks,
      while 95.40% at -75 degrees C. We suggest that blueberry juice color can be
      protected by keeping the extraction temperature below 60 degrees C with the
      selective addition of glucose, galactose, or citric acid. For long-term storage,
      it is recommended to use a light-protected container and a deep freezer at -75
      degrees C.

PMID- 29662848
TI  - Cooking Characteristics and Antioxidant Activity of Rice-Barley Mix at Different
      Cooking Method and Mixing Ratio.
AB  - This study aimed to compare the phenolic compounds and antioxidant activity of
      barley at different proportion (0, 5, 10, 15, and 20%), and using different
      cooking methods. The grains used in this experiment are barley (Hordeum vulgare
      L. cv. Huinchalssal) and Samkwang rice. The rice-barley mixture was cooked using
      general and high pressure cooking methods with and without fermented alcohol. The
      quality characteristics such as water binding capacity, pasting characteristic,
      water solubility, and swelling power of different proportions of barley were
      evaluated. The antioxidant characteristics evaluated are total polyphenol,
      flavonoid contents, 2,2-diphenyl-1-picrylhydrazyl (DPPH), and 2,2-azinobis(3
      ethylbenothiazoline-6-sulphonic acid) (ABTS) diammonium salt radical scavenging
      activities. Results showed that peak [195.0~184.0 rapid visco units (RVU)],
      trough (130.0~116.2 RVU), final (252.0~221.8 RVU), and setback viscosity
      (57.0~37.5 RVU) decreased correspondingly with the increase in the amount of
      barley. Water binding capacity (187.31~136.01%) and swelling power
      (162.37~127.58%) decreased as amounts of barley increases, however the water
      solubility (5.35~6.89%) increased. Moreover, the total polyphenol and flavonoid,
      and the DPPH and ABTS radical scavenging activities contents increased as the
      amounts of barley in the mixture increases. This study generally aims to provide
      useful information for the manufacturing of processed products.

PMID- 29662849
TI  - Dextran-Conjugated Lysozymes Inhibit the Growth of Shigella sonnei and Viral
      Hemorrhagic Septicemia Virus.
AB  - Lysozyme is well known as a natural antimicrobial agent, but its function is
      limited in that it only combats Gram-positive bacteria. We investigated the
      inhibitory effects of dextran-conjugated lysozymes (DLs) against some strains of
      Gram-negative bacteria and viral hemorrhagic septicemia virus (VHSV). The
      Maillard reactions of the DL were performed at various pHs (3.0, 7.0, and 8.5) in
      the presence of saturated KBr solution for 1, 3, 5, 7, and 9 days. The growth
      inhibition effects against Gram-negative bacterial strains, such as Escherichia
      coli, Vibrio parahaemolyticus, Pseudomonas aeruginosa, Shigella sonnei, and
      Shigella flexneri were found only in some DLs. DLs incubated at pH 7.0 for 9 days
      strongly inhibited growth of S. sonnei (92.9%). Fathead minnow (FHM) cells were
      infected with VHSV. DLs treated at all pHs for 1 day resulted in more than 80%
      viability of VHSV-infected FHM cells. The results of this study suggest that our
      DLs can be useful in food preservatives, pharmaceuticals, or aquatic feed due to
      their inhibitory effects against pathogenic bacteria and viral infections.

PMID- 29662850
TI  - Acute and Subacute Toxicity Evaluation of Corn Silk Extract.
AB  - Many studies have reported therapeutic efficacy of corn silk extract. However,
      research on its toxicity and safe dose range is limited. Thus, the objective of
      this study was to determine the acute and subacute toxicity of corn silk extract
      in ICR mice. To determine acute toxicity, corn silk extract containing high
      levels of maysin was orally administered to mice at a dose of 0 or 2,000 mg/kg.
      Clinical symptoms, mortality, and body weight changes were recorded for 14 days.
      To determine subacute toxicity, corn silk extract was orally administered to mice
      over a 4-week period, and then body weight, water and food consumption, and organ
      weight were determined. In addition, urine and serum analyses were performed. In
      the acute toxicity study, no death or abnormal symptoms was observed in all
      treatment groups during the study period. Body weights did not show any
      significant change compared to those of the control group. Lethal dose of corn
      silk extract was estimated to be more than 2,000 mg/kg. In the 4-week subacute
      toxicity study, there was no corn silk extract related toxic effect on body
      weight, water intake, food consumption, urine parameters, clinical chemistry, or
      organ weight. Histopathological examination showed no abnormality related to the
      administration of corn silk extract at 500 mg/kg. The maximum non-toxic dose of
      corn silk extract containing high levels of maysin was found to be more than 500
      mg/kg.

PMID- 29662851
TI  - Anti-Colitic Effect of Purple Carrot on Dextran Sulfate Sodium (DSS)-Induced
      Colitis in C57BL/6J Mice.
AB  - The anti-colitic effect of purple carrot (PC) on 2% dextran sulfate sodium (DSS)
      induced colitis in C57BL6/J mice was compared with those of yellow carrot (YC),
      beet (BT), and red cabbage (RC). Component analysis showed that PC contained
      cyanidin-3-xyloglucoside, cyanidin-3-xylosyl(sinapoly-glucosyl)galactoside,
      cyanidin-3-xylosyl(feruloylglucosyl) galactoside, and cyanidin-3-O-(6-O-glycosyl
      2-O-xylosylgalactoside). PC diet (5% in AIN 93G diet) strongly reduced DSS
      induced colon shortening and inflammatory cell infiltration in mice, followed by
      RC, BT, and YC diets. Treatment with PC reduced serum levels of pro-inflammatory
      cytokines such as tumor necrosis factor-alpha and interleukin-6 as well as
      reduced mRNA expression in colon tissue of colitis mice in comparison with other
      treatments. In addition, PC treatment inhibited colonic mRNA expression of
      inflammatory factors such as inducible nitric oxide synthase and cyclooxygenase-2
      in mice. These results suggest that PC can attenuate the inflammatory reaction in
      mice with DSS-induced colitis, probably due to the anthocyanins in PC.

PMID- 29662852
TI  - Current treatment for pediatric acute myeloid leukemia.

PMID- 29662854
TI  - Plasma cells with Auer rod-like inclusions in a patient with myeloma.

PMID- 29662853
TI  - The role of allogeneic hematopoietic stem cell transplantation in the four P
      medicine era.

PMID- 29662855
TI  - A weeping ulcer that vanished with a 'SMILE'.

PMID- 29662856
TI  - Renal cell carcinoma metastasizing to the myeloproliferative bone marrow.

PMID- 29662857
TI  - Cryohemolysis, erythrocyte osmotic fragility, and supplementary hematimetric
      indices in the diagnosis of hereditary spherocytosis.
AB  - Background: Hereditary spherocytosis (HS) is a chronic hemolytic anemia
      characterized by microspherocytes in the peripheral blood and increased
      erythrocyte osmotic fragility (EOF). This study evaluated the cryohemolysis test
      (CHT); initial hemolysis (IH); immediate and incubated hemolysis percentage in
      5.5 g/L NaCl (H5.5); mean corpuscular hemoglobin concentration (MCHC); red blood
      cell distribution width (RDW); and Hb/MCHC, Hb/RDW, and MCHC/RDW ratios for the
      diagnosis of HS. Methods: Data from 13 patients with HS were evaluated at the
      Instituto de Bioquimica Aplicada and compared with data from 14 unaffected
      individuals and 11 patients with anemia due to another etiology. Total blood and
      reticulocyte counts, CHT, and immediate and incubated EOF were performed in all
      subjects; sensitivity, specificity, efficiency, and Youden index (YI) were
      calculated. Results: Eight patients with HS had MCHC >=345 g/L, 10 had RDW
      >=14.5%, 12 had IH >5.0 g/L, 11 had immediate H5.5 >=5%, and 13 had incubated
      H5.5 >=50% (the cut-off value to consider HS). The efficiency and YI were:
      immediate H5.5 (0.94-0.85), incubated H5.5 (0.89-0.82), IH (0.89-0.78), MCHC
      (0.87-0.62), CHT (0.84-0.54), and Hb/MCHC (0.71-0.56), respectively. The
      calculated ratios could distinguish subjects with HS from unaffected individuals
      (P<0.05), but not those with anemia of another etiology (P>0.05). Conclusion:
      Although the CHT and supplementary hematimetric indexes were useful to
      differentiate individuals with SH from healthy controls, they cannot distinguish
      from anemias of other etiology. CHT and MCHC, in addition to EOF, are recommended
      for diagnosing HS patients because of their low cost and efficiency.

PMID- 29662858
TI  - Reference values for serum ferritin and percentage of transferrin saturation in
      Korean children and adolescents.
AB  - Background: Ferritin reference values vary by age, gender, and ethnicity. We
      aimed to determine reference values of serum ferritin (SF) and the percentage of
      transferrin saturation (TSAT) for Korean children and adolescents. Methods: We
      analyzed data from 2,487 participants (1,311 males and 1,176 females) aged 10-20
      years from the Korea National Health and Nutrition Examination Survey (2010
      2012). We calculated age- and gender-stratified means and percentile values for
      SF and TSAT. Results: We first plotted mean SF and TSAT by gender and according
      to age. In males, mean SF tended to be relatively constant among participants
      aged 10 to 14 years, with an upward trend thereafter. Mean SF trended downward
      among female participants until the age of 15 years and remained constant
      thereafter. Thus, significant gender differences in ferritin exist from the age
      of 14 years. High levels of SF were associated with obesity, and lower SF levels
      were associated with anemia and menarche status. Conclusion: We established
      reference values of SF and TSAT according to age and gender. The reference values
      for SF calculated in this study can be used to test the association between SF
      values and other defined diseases in Korean children and adolescents.

PMID- 29662859
TI  - Improvement of treatment outcome over 2 decades in children with acute myeloid
      leukemia.
AB  - Background: The prognosis of pediatric acute myeloid leukemia (AML) has recently
      improved. This study aimed to describe the epidemiology, changes in treatment
      strategies, and improvement of outcomes in Gwangju-Chonnam children with AML over
      2 decades. Methods: Medical records of 116 children with newly diagnosed AML were
      retrospectively reviewed for demographic characteristics, prognostic groups
      including cytogenetic risks, treatment protocols, and survival rates over the
      periods between 1996 and 2005 (Period I, N=53), and 2006 and 2015 (Period II,
      N=38). Results: The annual incidence of AML has decreased with reduced pediatric
      population. The 5-year Kaplan-Meier (K-M) estimated overall survival (OS) and
      event-free survival (EFS) rates in 110 AML patients were 53.2+/-5.1% and 43.8+/
      5.1%, respectively. The 5-year OS rate significantly improved during period II
      (70.3+/-7.0%) as compared to that during period I (40.0+/-6.8%) (P =0.001). The 5
      year OS was not significantly different among cytogenetic risk groups (P =0.11).
      Fifty-eight patients underwent hematopoietic stem cell transplantation (HSCT).
      The K-M 5-year estimated survival for transplanted patients was 53.7+/-7.0%,
      while that for chemotherapy-only patients was 30.1+/-9.1% (P =0.014). Among the
      prognostic factors, treatment modality was the only independent factor. The
      chemotherapy-only group had a relative risk of 2.06 for death compared with the
      transplantation group (P=0.015). Conclusion: The survival of Korean children with
      AML has improved to a level comparable with that of developed countries over 2
      decades, owing to a change in induction strategy, better supportive care with
      economic growth, refinement of HSCT techniques including a better selection of
      patients based on prognostic groups, and stem cell donor selection.

PMID- 29662861
TI  - Global hemostatic assay of different target procoagulant activities of factor
      VIII and factor IX.
AB  - Background: Korean National Health Insurance reimburses factor VIII (FVIII) and
      factor IX (FIX) clotting factor concentrate (CFC) infusions to discrepant
      activity levels, allowing elevation of FVIII activity to 60 IU/dL and FIX to 40
      IU/dL. We aimed to assess hemostatic response to these target levels using global
      hemostatic assays. Methods: We enrolled 34 normal healthy men, 34 patients with
      hemophilia A, and 36 with hemophilia B, with residual factor activity of 3 IU/dL
      or less and without inhibitors. Patients with hemophilia A and B received
      injected CFCs according to reimbursement guidelines. Fifteen minutes after
      injection, we assessed hemostatic response with global hemostatic assays:
      thrombin generation assay (TGA), thromboelastography (TEG), and clot waveform
      analysis (CWA). Results: Normal healthy men and patients with hemophilia A and B
      were 36.7, 37.2, and 35.1 years old, respectively. FVIII and recombinant FIX
      concentrate doses were 28.8 IU/kg and 43.6 IU/kg. Post-infusion FVIII activity
      rose from 0.5 IU/dL to 69.4 IU/dL, while FIX activity rose from 1.4 IU/dL to 46.8
      IU/dL. Post-infusion peak thrombin concentrations in hemophilia A and B were
      116.6 nM/L and 76.4 nM/L (P<0.001). Post-infusion endogenous thrombin potential
      (ETP) in hemophilia A and B was 1349.8 nM/min and 915.6 nM (P<0.001). TEG index
      of hemophilia A and B was 0.11 and -0.51 (P=0.006). Conclusion: Current
      reimbursed doses for FIX concentrates are insufficient to achieve hemostatic
      responses comparable to those after reimbursed doses for FVIII concentrates in
      terms of peak thrombin concentration, ETP, and TEG index.

PMID- 29662860
TI  - Splenic myeloid metaplasia in warm autoimmune hemolytic anemia (wAIHA): a
      retrospective study.
AB  - Background: Splenic myeloid metaplasia (SMM) is a kind of extramedullary
      hematopoiesis, whereas its clinical significance in wAIHA remains unclear. The
      aim of this study is evaluating the frequency and clinical characteristics of
      SMM, compared with splenic-congestion (SC). Methods: We included patients with
      wAIHA treated in a Mexican tertiary hospital between January 1992 and December
      2015. All patients received steroids as first-line treatment and splenectomy as
      second-line treatment. Results: Among the thirty-six splenectomized patients, 15
      (41.6%) and 21 (58.4%) were diagnosed as SMM and SC, respectively. No differences
      were found in clinical characteristics between two groups. SMM patients showed
      lower platelet count (147*109/L vs. 240*109/L, P=0.02) and higher presence of
      anti-dsDNA antibodies (40% vs. 4.7%, P=0.01) than SC patients. Although the
      complete response (CR) rate with first-line treatment was lower in SMM patients
      (13.3% vs. 47.6%; P=0.04), post-splenectomy median disease-free-survival (DFS)
      was longer (16.2 mo vs. 5.1 mo; P=0.19). Univariate/multivariate analysis showed
      that achieving CR during first-line treatment (OR 0.3, 95% CI: 0.03-0.94, P=0.03)
      and higher platelet count (OR 0.99, 95% CI: 0.98-0.99, P=0.03) were protective
      factors for SMM; and anti-dsDNA titer higher than 9.6 IU/dL was a risk factor for
      SMM (OR 2.76, 95% CI: 1.48-5.14, P<0.001). Conclusion: The wAIHA patients with
      SMM have different biological profiles with those without SMM. This study is the
      first trial evaluating the significance of histopathological spleen findings and
      their association with rheumatologic profile.

PMID- 29662862
TI  - Additional cytogenetic aberrations in chronic myeloid leukemia: a single-center
      experience in the Middle East.
AB  - Background: Additional cytogenetic aberrations are associated with disease
      progression in chronic myeloid leukemia (CML). This study was conducted to
      determine the type and frequency of these aberrations and their relationship with
      hematologic and molecular findings in the Middle East. Methods: In this
      retrospective study, 134 well-established cases of CML were selected from 2010 to
      2016. Their hematologic phase and type of fusion gene were determined. Finally,
      their karyotypes were analyzed and reported according to ISCN 2013. Results:
      Patients had a mean age of 44 years. Twenty-two patients (16.4%) showed
      additional cytogenetic aberrations. Nine patients (6.7%) harbored a variant
      Philadelphia chromosome, and most were in the chronic phase. Seventeen patients
      (12.7%) had major and minor route abnormalities. There was a significant
      relationship between additional cytogenetic aberrations and major molecular
      response (P=0.032). Patient survival in the group with additional cytogenetic
      aberrations was significantly lower (49.7+/-11.1 mo) than that in the group
      without additional cytogenetic aberrations (77.3+/-3.1 mo) (P=0.031). Conclusion:
      This study revealed the same frequency of additional cytogenetic aberrations in
      CML as found in previous studies. Additional chromosomal aberrations led to
      shorter survival and lower rates of achievement of a major molecular response.

PMID- 29662863
TI  - Investigation of BAX and BCL2 expression and apoptosis in a resveratrol- and
      prednisolone-treated human T-ALL cell line, CCRF-CEM.
AB  - Background: The numerous side effects and chemo-resistance of conventional
      chemical drugs in the treatment of malignancies have led to consideration of the
      anti-cancer properties of natural products. In the present study, we aimed to
      explore the apoptotic effect of two natural components, resveratrol and
      prednisolone, on the T acute lymphoblastic leukemia (ALL) cell line, CCRF-CEM.
      Our findings suggested the incorporation of these natural agents into drug
      regimens to treat patients with ALL. Methods: In this study, we investigated the
      effect of different doses of resveratrol (15, 50 and 100 uM) and prednisolone
      (700 uM) on BAX (apoptosis promoter) and BCL2 (apoptosis inhibitor) expressions
      following 24 and 48 hours of treatment on CCRF-CEM cells, using real-time PCR,
      and on apoptosis induction using flow cytometry. Results: The results showed a
      time- and dose-dependent increase in BAX expression and a decrease in BCL2
      expression. Apoptosis was induced in CCRF-CEM cells treated with resveratrol and
      prednisolone for 24 and 48 hours. Combined resveratrol and prednisolone treatment
      showed synergistic effects on the overexpression of BAX and the downregulation of
      BCL2. The drug combination had a greater influence on apoptosis induction
      compared with either drug administered alone after 48 hours of treatment.
      Conclusion: The results of this study suggested that resveratrol exhibited a
      remarkable efficacy to improve the influence of glucocorticoids drugs, especially
      prednisolone, to induce apoptosis in the CCRF-CEM cell line.

PMID- 29662864
TI  - Expression of adhesion molecules on CD34+ cells from steady-state bone marrow
      before and after mobilization and their association with the yield of CD34+
      cells.
AB  - Background: Cell adhesion molecules (CAMs) expressed on hematopoietic progenitor
      cells (HPCs), endothelial cells, and stromal cells play a pivotal role in the
      mobilization of CD34+ cells. Herein, we conducted a non-randomized peripheral
      blood stem cell (PBSC) mobilization study aimed to compare the potential
      differences in the expressions of several CAMs and chemokines on CD34+ cells
      obtained from bone marrow aspirate before and after HPC mobilization from
      patients with hematologic malignancies and healthy donors. Methods: Three-color
      cytofluorometric analysis was used to compare the expressions of CAMs and
      chemokines in the bone marrow before and after mobilization. Results: For all
      studied groups, CAM expression among those with good and poor yields of CD34+
      cells was significantly correlated with VCAM-1 (P=0.007), CD44 (P=0.027), and VLA
      4 (P=0.014) expressions. VCAM-1 (P=0.001), FLT-3 (P=0.001), CD44 (P=0.011), VLA-4
      (P=0.001), and LFA-1 (P=0.001) expressions were higher before HPC mobilization
      than after HPC mobilization. By contrast, the expression of CXCR4 significantly
      varied before and after mobilization only among those with successful PBSC
      mobilization (P=0.002). Conclusion: We attempted to identify particular aspects
      of CAMs involved in CD34+ cell mobilization, which is a highly complex mechanism
      that involves adhesion molecules and matrix metalloproteases. The mechanism by
      which CD34+ cell mobilization is activated through proteolytic enzymes is not
      fully understood. We believe that CXCR4, VLA-4, CD44, and VCAM-1 are the most
      important molecules implicated in HPC mobilization, particularly because they
      show a correlation with the yield of CD34+ cells collected via large volume
      leukapheresis.

PMID- 29662865
TI  - Successful rapid drug desensitization to methotrexate in a patient with primary
      central nervous system lymphoma.

PMID- 29662866
TI  - A rare case of splenic diffuse red pulp small B-cell lymphoma (SDRPL): a review
      of the literature on primary splenic lymphoma with hairy cells.

PMID- 29662867
TI  - An unusual etiology of plummer-Vinson syndrome.

PMID- 29662868
TI  - Pulmonary embolism presenting with acute abdominal pain in a girl with stable
      ankle fracture and inherited antithrombin deficiency.

PMID- 29662869
TI  - A case of adult T-cell leukemia/lymphoma in Korea.

PMID- 29662870
TI  - Primary CNS high-grade B-cell lymphoma, with rearrangements of MYC and BCL6 : a
      case report.

PMID- 29662871
TI  - Cancer associated phlegmasia cerulea dolens successfully treated with apixaban.

PMID- 29662872
TI  - A rare variant of t(17;19) in a case of Philadelphia positive adult acute
      lymphoblastic leukemia presenting with disseminated intravascular coagulation.

PMID- 29662873
TI  - Permissive Hypercapnia Results in Decreased Functional Vessel Density in the Skin
      of Extremely Low Birth Weight Infants.
AB  - Background: Ventilator-induced lung injury with subsequent bronchopulmonary
      dysplasia remains an important issue in the care of extremely low-birth-weight
      infants. Permissive hypercapnia has been proposed to reduce lung injury.
      Hypercapnia changes cerebral perfusion, but its influence on the peripheral
      microcirculation is unknown. Methods: Data were collected from 12 infants, who
      were randomized to a permissive high PCO2 target group (HTG) or a control group
      (CG). Inclusion criteria were birth weight between 400 and 1,000 g, gestational
      age from 23 to 28 6/7 weeks, intubation during the first 24 h of life, and no
      malformations. The PCO2 target range was increased stepwise in both groups for
      weaning and was always 15 mmHg higher in the HTG than in the CG. Skin
      microvascular parameters were assessed non-invasively with sidestream dark field
      imaging on the inner side of the right arm every 24 h during the first week of
      life and on the 14th day of life. Results: Infants in the HTG had significantly
      higher max. PCO2 exposure, which was associated with a significantly and
      progressively reduced functional vessel density (FVD, p < 0.01). Moreover, there
      were significant differences in the diameter distribution over time, with HTG
      subjects having fewer small vessels but more large vessels. Conclusion: High PCO2
      levels significantly impaired peripheral microcirculation in preterm infants, as
      shown by a decreased FVD, presumably secondary to peripheral vasoconstriction.
      ISRCTN: 56143743.

PMID- 29662875
TI  - Positive Virological Outcomes of HIV-Infected Patients on Protease Inhibitor
      Based Second-Line Regimen in Cambodia: The ANRS 12276 2PICAM Study.
AB  - Background: Assessment of virological outcomes among HIV-infected patients
      receiving protease (PR) inhibitor-based second-line regimen are uncommon in
      Cambodia. The objective of this study is to assess the virological effectiveness
      of this regimen as well as impact of adherence boosting for patients experiencing
      virological failure. Methods: The 2PICAM study (Clinicaltrial: NCT01801618) is a
      cross-sectional study of HIV-infected adults on PR inhibitor-based second-line
      regimen since at least 6 months, conducted in 13 representative sites, comprising
      more than 90% of the target population. Adults with HIV RNA above 250 copies/mL
      (threshold of the assay) at inclusion received boosted adherence counseling
      during 3 months followed by HIV RNA control. For confirmed virological failure,
      genotype resistance test was performed and expert committee used results for
      therapeutic decision. Results: Among the 1,317 adults enrolled, the median
      duration of second-line regimen was 5 years. At inclusion, 1,182 (89.7%) patients
      achieved virological success (<250 copies/mL) and 135 (10.3%) experienced a
      virological failure (>250 copies/mL). In multivariable analysis, factors
      associated with virological success were: CD4 cell count between 201 and 350/mm3
      (OR: 4.66, 95% CI: 2.57-8.47, p < 0.0001) and >350/mm3 (OR: 6.67, 95% CI: 4.02
      11.06, p < 0.0001), duration of PI-based regimen >2 years (OR: 1.64, 95% CI: 1.03
      2.62, p = 0.037), ATV-containing regimen (0R: 1.65, 95% CI: 1.04-2.63, p = 0.034)
      and high level of adherence (OR: 2.41, 95% CI: 1.07-5.41, p = 0.033). After
      adherence counseling, 63 (46.7%) patients were rescued while 72 (53.3%) were not.
      For the 54 patients with genotype resistance tests available, high or
      intermediate levels of resistance to lopinavir, atazanavir, and darunavir were
      reported for 13 (24%), 12 (22.2%), and 2 (3.7%) patients, respectively. Change to
      an alternative PR inhibitor-based regimen was recommended for 17 patients and to
      third-line regimen, including integrase inhibitors for 12. Conclusion: This study
      reports high rate of virological suppression of second-line regimen and
      importance of adherence boosting prior to deciding any change of ART regimen.
      Genotype resistance tests appear necessary to guide decisions. Such information
      was of great importance for National HIV Program to adapt guidelines and program
      needs for third-line regimen.

PMID- 29662876
TI  - Mapping Health Needs to Support Health System Management in Poland.
AB  - In Poland, following the example of other EU countries, the first maps of health
      needs prepared by the Ministry of Health were presented in 2016. The maps
      constitute a foundation for rational decision-making in the management of health
      care resources, being potentially useful for all actors in health system. This
      refers in particular to the institutions responsible for distribution of funds
      and contracting health service, but also for decision-makers, who determine the
      scope of funds to be utilized in the health system, or the structure of benefits
      provided to patients. Service providers are also addressees of the maps, to give
      them a basis for planning future activities. The article presents a structured
      assessment of the current state of affairs, based on recent experience and sets
      out likely directions for the development of health needs in mapping in Poland in
      the future. We discuss the criticism addressed toward maps by representatives of
      various groups acting in health care. It includes the lack of recognition of some
      of the key health needs, or wrong emphases, where much more attention is paid to
      the recognition of current resources in the health system, instead of making
      prognoses regarding the future developments of health needs. Nonetheless, we find
      that this instrument is potentially of high usability, in case of elimination of
      the existing weaknesses.

PMID- 29662874
TI  - Prevalent emm Types among Invasive GAS in Europe and North America since Year
      2000.
AB  - Background: Streptococcus pyogenes or group A streptococcus (GAS) is an important
      human pathogen responsible for a broad range of infections, from uncomplicated to
      more severe and invasive diseases with high mortality and morbidity.
      Epidemiological surveillance has been crucial to detect changes in the
      geographical and temporal variation of the disease pattern; for this purpose the
      M protein gene (emm) gene typing is the most widely used genotyping method, with
      more than 200 emm types recognized. Molecular epidemiological data have been also
      used for the development of GAS M protein-based vaccines. Methods: The aim of
      this paper was to provide an updated scenario of the most prevalent GAS emm types
      responsible for invasive infections in developed countries as Europe and North
      America (US and Canada), from 1st January 2000 to 31st May 2017. The search,
      performed in PubMed by the combined use of the terms ("emm") and ("invasive")
      retrieved 264 articles, of which 38 articles (31 from Europe and 7 from North
      America) met the inclusion criteria and were selected for this study. Additional
      five papers cited in the European articles but not retrieved by the search were
      included. Results: emm1 represented the dominant type in both Europe and North
      America, replaced by other emm types in only few occasions. The seven major emm
      types identified (emm1, emm28, emm89, emm3, emm12, emm4, and emm6) accounted for
      approximately 50-70% of the total isolates; less common emm types accounted for
      the remaining 30-50% of the cases. Most of the common emm types are included in
      either one or both the 26-valent and 30-valent vaccines, though some well
      represented emm types found in Europe are not. Conclusion: This study provided a
      picture of the prevalent emm types among invasive GAS (iGAS) in Europe and North
      America since the year 2000 onward. Continuous surveillance on the emm-type
      distribution among iGAS infections is strongly encouraged also to determine the
      potential coverage of the developing multivalent vaccines.

PMID- 29662877
TI  - Soluble Molecularly Imprinted Nanorods for Homogeneous Molecular Recognition.
AB  - Nowadays, it is still difficult for molecularly imprinted polymers (MIPs) to
      achieve homogeneous recognition since they cannot be easily dissolved in organic
      or aqueous phase. To address this issue, soluble molecularly imprinted nanorods
      have been synthesized by using soluble polyaniline doped with a functionalized
      organic protonic acid as the polymer matrix. By employing 1-naphthoic acid as a
      model, the proposed imprinted nanorods exhibit an excellent solubility and good
      homogeneous recognition ability. The imprinting factor for the soluble imprinted
      nanoroads is 6.8. The equilibrium dissociation constant and the apparent maximum
      number of the proposed imprinted nanorods are 248.5 MUM and 22.1 MUmol/g,
      respectively. We believe that such imprinted nanorods may provide an appealing
      substitute for natural receptors in homogeneous recognition related fields.

PMID- 29662878
TI  - Selective Detection of Lysozyme Biomarker Utilizing Large Area Chemical Vapor
      Deposition-Grown Graphene-Based Field-Effect Transistor.
AB  - Selective and rapid detection of biomarkers is of utmost importance in modern day
      health care for early stage diagnosis to prevent fatal diseases and infections.
      Among several protein biomarkers, the role of lysozyme has been found to be
      especially important in human immune system to prevent several bacterial
      infections and other chronic disease such as bronchopulmonary dysplasia. Thus,
      real-time monitoring of lysozyme concentration in a human body can pave a facile
      route for early warning for potential bacterial infections. Here, we present for
      the first time a label-free lysozyme protein sensor that is rapid and selective
      based on a graphene field-effect transistor (GFET) functionalized with
      selectively designed single-stranded probe DNA (pDNA) with high binding affinity
      toward lysozyme molecules. When the target lysozyme molecules bind to the surface
      immobilized pDNAs, the resulting shift of the charge neutrality points of the
      GFET device, also known as the Dirac voltage, varied systematically with the
      concentration of target lysozyme molecules. The experimental results show that
      the GFET-based biosensor is capable of detecting lysozyme molecules in the
      concentration range from 10 nM to 1 uM.

PMID- 29662879
TI  - Abnormal Elongations of HOX Gene Clusters May Cause Cancer.

PMID- 29662880
TI  - Common Evaluations of Disease Activity in Rheumatoid Arthritis Reach Discordant
      Classifications across Different Populations.
AB  - Objectives: The classification of disease activity states in rheumatoid arthritis
      (RA) can be achieved through disease activity indices, such as the Disease
      Activity Score in 28 joints erythrocyte sedimentation rate (DAS28-ESR), the
      Simplified Disease Activity Index (SDAI), and the Clinical Disease Activity Index
      (CDAI). Subjective measurements, such as patient reported outcomes have been
      incorporated into several of these indices alongside more objective assessments,
      such as increases in the ESR and C-reactive protein. Moreover, while they use
      similar criteria, different indices weight these criteria to different extents.
      Therefore, the classifications based on each evaluation may not always be the
      same. We aim to compare the performance of the three indices and their individual
      components in two different populations. Methods: Data from Dutch and Portuguese
      adherent centers were extracted from the METEOR database, a multinational
      collaboration on RA. We included a total of 24,605 visits from Dutch centers
      (from 5,870 patients) and 20,120 visits from Portuguese centers (from 3,185
      patients). We compared the disease activity states as evaluated by the DAS28-ESR,
      CDAI, and SDAI across the two populations. In addition, we analyzed the
      individual components of each evaluation, including their respective
      contributions to the outcome, in each population. Results: We found significant
      differences in the disease activity states classified with the DAS28-ESR between
      the two populations. SDAI and CDAI had more congruous results. While the
      proportion of visits to Dutch and Portuguese centers that were classified as "in
      remission" was very similar between the CDAI and SDAI, the DAS28-ESR gave
      discordant results. Dutch patients had lower ESRs, which is more heavily weighted
      in the DAS28-ESR. In addition, even though the mean physicians' global assessment
      values did not vary significantly for Dutch vs Portuguese physicians, we found
      that doctors at Portuguese centers overall scored the physician's global
      assessment lower than Dutch physicians for patient visits classified by disease
      activity state. Conclusion: While the CDAI and SDAI assigned disease activity
      states that were largely similar, the DAS28-ESR was often discordant across the
      two populations. Moreover, we found that physicians, more than patients,
      evaluated disease activity differently among the Portuguese and Dutch
      populations.

PMID- 29662882
TI  - Circulatory Arrest, Brain Arrest and Death Determination.
AB  - Technological advances, particularly in the capacity to support, replace or
      transplant failing organs, continue to challenge and refine our understanding of
      human death. Given the ability to reanimate organs before and after death, both
      inside and outside of the body, through reinstitution of oxygenated circulation,
      concepts related to death of organs (e.g. cardiac death) are no longer valid.
      This paper advances the rationale for a single conceptual determination of death
      related to permanent brain arrest, resulting from primary brain injury or
      secondary to circulatory arrest. The clinical characteristics of brain arrest are
      the permanent loss of capacity for consciousness and loss of all brainstem
      functions. In the setting of circulatory arrest, death occurs after the arrest of
      circulation to the brain rather than death of the heart. Correspondingly, any
      intervention that resumes oxygenated circulation to the brain after circulatory
      arrest would invalidate the determination of death.

PMID- 29662883
TI  - Long Non-Coding RNAs in Vascular Inflammation.
AB  - Less than 2% of the genome encodes for proteins. Accumulating studies have
      revealed a diverse set of RNAs derived from the non-coding genome. Among them,
      long non-coding RNAs (lncRNAs) have garnered widespread attention over recent
      years as emerging regulators of diverse biological processes including in
      cardiovascular disease (CVD). However, our knowledge of their mechanisms by which
      they control CVD-related gene expression and cell signaling pathways is still
      limited. Furthermore, only a handful of lncRNAs has been functionally evaluated
      in the context of vascular inflammation, an important process that underlies both
      acute and chronic disease states. Because some lncRNAs may be expressed in cell-
      and tissue-specific expression patterns, these non-coding RNAs hold great promise
      as novel biomarkers and as therapeutic targets in health and disease. Herein, we
      review those lncRNAs implicated in pro- and anti-inflammatory processes of acute
      and chronic vascular inflammation. An improved understanding of lncRNAs in
      vascular inflammation may provide new pathophysiological insights in CVD and
      opportunities for the generation of a new class of RNA-based biomarkers and
      therapeutic targets.

PMID- 29662884
TI  - Transmission of Helminths between Species of Ruminants in Austria Appears More
      Likely to Occur than Generally Assumed.
AB  - Helminth infections of the gastrointestinal tract and lungs can lead to
      devastating economical losses to the pastoral based animal production. Farm
      animals can suffer from malnutrition, tissue damage, and blood loss resulting in
      impaired production traits and reproduction parameters. In Austria, pastures
      grazed by sheep, goats, and cattle overlap with the habitats of several species
      of wild cervids (roe deer, red deer, sika deer, and fallow deer) and bovids
      (mouflon, chamois, and ibex), and transmission of parasites between different
      ruminant species seems likely. A complete and updated overview on the occurrence
      of helminths of domestic and wild ruminants in Austria is presented. Based on
      these data, intersections of the host spectrum of the determined parasites were
      depicted. The "liability index" was applied to identify the ruminant species,
      which most likely transmit parasites between each other. A degree for host
      specificity was calculated for each parasite species based on the average
      taxonomic distance of their host species. Of the 73 identified helminth species
      42 were identified as generalists, and 14 transmission experiments supported the
      assumed broad host specificity for 14 generalists and 1 specialist helminth
      species. Overall, 61 helminths were found to infect more than one host species,
      and 4 were found in all 10 ruminant species investigated. From these analyses, it
      can be concluded that a number of helminth parasites of the gastrointestinal
      tract and the lungs are potentially transmitted between domestic and wild
      ruminants in Austria. For some parasites and host species, experimental evidence
      is in support for possible transmission, while for other such studies are
      lacking. Host preference of different genotypes of the same parasite species may
      have a confounding effect on the evaluation of cross-transmission, but so far
      this has not been evaluated systematically in helminths in Austria. Further
      studies focusing on experimental cross-transmission and genetic characterization
      are needed to define the potential consequences for the epidemiology of those
      parasites, animal welfare, and economic impact.

PMID- 29662885
TI  - Investigation of Echinococcus multilocularis in Environmental Definitive Host
      Feces in the Asian and the European Parts of Turkey.
AB  - A study was carried out to investigate the presence of Echinococcus
      multilocularis in red foxes (Vulpes vulpes) in two regions of Turkey-central
      Anatolia (in Asia Minor) and Thrace (in the European part of Turkey). A total of
      405 putative fox feces were collected from central Anatolia (186 specimens in 59
      locations) and from Thrace (219 specimens in 114 locations). All samples were
      examined by the flotation and sieving method for taeniid eggs, and positive and
      putative samples were further analyzed by multiplex PCR. In seven samples from
      three locations in central Anatolia (5.1%) and in one (0.9%) from Thrace, E.
      multilocularis DNA was amplified, and this result was confirmed with another PCR
      specific for E. multilocularis. In addition, Echinococcus granulosus s.l. was
      found in two (0.5%) of the samples. Although alveolar echinococcosis (AE) is
      known as a serious zoonosis in Turkey, this is the first field study detecting E.
      multilocularis in collected fecal samples documenting the environmental
      contamination with eggs of this zoonotic parasite.

PMID- 29662881
TI  - The Continuum of Aging and Age-Related Diseases: Common Mechanisms but Different
      Rates.
AB  - Geroscience, the new interdisciplinary field that aims to understand the
      relationship between aging and chronic age-related diseases (ARDs) and geriatric
      syndromes (GSs), is based on epidemiological evidence and experimental data that
      aging is the major risk factor for such pathologies and assumes that aging and
      ARDs/GSs share a common set of basic biological mechanisms. A consequence is that
      the primary target of medicine is to combat aging instead of any single ARD/GSs
      one by one, as favored by the fragmentation into hundreds of specialties and sub
      specialties. If the same molecular and cellular mechanisms underpin both aging
      and ARDs/GSs, a major question emerges: which is the difference, if any, between
      aging and ARDs/GSs? The hypothesis that ARDs and GSs such as frailty can be
      conceptualized as accelerated aging will be discussed by analyzing in particular
      frailty, sarcopenia, chronic obstructive pulmonary disease, cancer,
      neurodegenerative diseases such as Alzheimer and Parkinson as well as Down
      syndrome as an example of progeroid syndrome. According to this integrated view,
      aging and ARDs/GSs become part of a continuum where precise boundaries do not
      exist and the two extremes are represented by centenarians, who largely avoided
      or postponed most ARDs/GSs and are characterized by decelerated aging, and
      patients who suffered one or more severe ARDs in their 60s, 70s, and 80s and show
      signs of accelerated aging, respectively. In between these two extremes, there is
      a continuum of intermediate trajectories representing a sort of gray area. Thus,
      clinically different, classical ARDs/GSs are, indeed, the result of peculiar
      combinations of alterations regarding the same, limited set of basic mechanisms
      shared with the aging process. Whether an individual will follow a trajectory of
      accelerated or decelerated aging will depend on his/her genetic background
      interacting lifelong with environmental and lifestyle factors. If ARDs and GSs
      are manifestations of accelerated aging, it is urgent to identify markers capable
      of distinguishing between biological and chronological age to identify subjects
      at higher risk of developing ARDs and GSs. To this aim, we propose the use of DNA
      methylation, N-glycans profiling, and gut microbiota composition to complement
      the available disease-specific markers.

PMID- 29662886
TI  - High Prevalence of Extended-Spectrum beta-Lactamase Producing Enterobacteriaceae
      Among Clinical Isolates From Cats and Dogs Admitted to a Veterinary Hospital in
      Switzerland.
AB  - Objectives: This study aimed to identify and characterize extended-spectrum beta
      lactamase (ESBL) producing Enterobacteriaceae among clinical samples of companion
      animals. Methods: A total of 346 non-duplicate Enterobacteriaceae isolates were
      collected between 2012 and 2016 from diseased cats (n = 115) and dogs (n = 231).
      The presence of blaESBL, PMQR genes, and the azithromycin resistance gene mph(A)
      was confirmed by PCR and sequencing of bla genes. Isolates were further
      characterized by antimicrobial resistance profiling, multilocus sequence typing,
      phylogenetic grouping, identification of mutations in the QRDR of gyrA and parC,
      and screening for virulence-associated genes. Results: Among the 346 isolates, 72
      (20.8%) were confirmed ESBL producers [58 Escherichia coli (E. coli), 11
      Klebsiella pneumoniae (K. pneumoniae), and 3 Enterobacter cloacae]. The strains
      were cultured from urine (n = 45), skin and skin wounds (n = 8), abscesses (n =
      6), surgical sites (n = 6), bile (n = 4), and other sites (n = 3). ESBL genes
      included blaCTX-M-1, 14, 15, 27, 55, and blaSHV-12, predominantly blaCTX-M-15
      (54.8%, 40/73), and blaCTX-M-1 (24.7%, 18/73). Further genes included qnrB (4.2%,
      3/72), qnrS (9.7%, 7/72), aac(6')-Ib-cr (47.2%, 34/72), and mph(A) (38.9%,
      28/72). Seventeen (23.6%) isolates belonged to the major lineages of human
      pathogenic K. pneumoniae ST11, ST15, and ST147 and E. coli ST131. The most
      prevalent ST was E. coli ST410 belonging to phylogenetic group C. Conclusion: The
      high prevalence of ESBL producing clinical Enterobacteriaceae from cats and dogs
      in Switzerland and the presence of highly virulent human-related K. pneumoniae
      and E. coli clones raises concern about transmission prevention as well as
      infection management and prevention in veterinary medicine.

PMID- 29662887
TI  - Characteristics of Heat Illness during Hajj: A Cross-Sectional Study.
AB  - Introduction: Data regarding the characteristics and outcomes of heat illness are
      lacking in the literature. The present study aimed to identify the clinical
      characteristics, morbidity, management, and mortality associated with heat
      illness among Hajj participants. Methods: A cross-sectional study was conducted
      during the Hajj in 2016 on patients who presented to emergency departments and
      were diagnosed with heat exhaustion or heatstroke. Data were collected using a
      structured collection sheet developed based on the literature. Results: A total
      of 267 patients were recruited. Of these, 80 (29%) and 187 (67.75%) were
      diagnosed with heatstroke and heat exhaustion, with 6.3% and 0.0% mortality,
      respectively. The mean age of the patients was 54.0 +/- 16 years. Diabetes
      mellitus was the most common comorbidity among both heatstroke and heat
      exhaustion patients. The majority of patients had hyperthermia and electrolyte
      imbalance. Most of the heat illness cases were treated per heat illness
      guidelines. Conclusions: Although authorities are working on research and forming
      interdisciplinary teams to prevent health problems during the Hajj, the mortality
      rate from heatstroke is high and the majority of the patients had hyperthermia,
      varied signs and symptoms, elevated creatinine levels, and electrolyte
      imbalances.

PMID- 29662888
TI  - Prognostic Value of Immunoscore and PD-L1 Expression in Metastatic Colorectal
      Cancer Patients with Different RAS Status after Palliative Operation.
AB  - Colorectal cancer (CRC) is the fifth leading cause of cancer death and the fifth
      most commonly diagnosed cancer in China. Approximately, 25% of CRC was in the
      advanced stage as diagnosed, and 40% of patients with CRC progress to metastatic
      colorectal cancer (mCRC). RAS mutation status is now routinely used to select
      their therapy. But it is still a question whether RAS mutation status is a
      prognostic marker. In our study, we detected RAS mutation, immunoscore (IS), and
      PD-L1 expression in 60 Chinese mCRC patients who received palliative operation.
      The Kaplan-Meier survival analysis showed that the overall survival (OS) in
      patients with RAS wild type was better than those with RAS mutated type.
      Moreover, in multivariate analysis, RAS mutation and PD-L1 expression were
      demonstrated to be the independent negative prognostic factors for OS (P = 0.044,
      HR: 0.258, and 95% CI: 0.069-0.967; P = 0.048, HR: 0.276, and 95% CI: 0.077
      0,988). All results suggested that, combined with IS, PD-L1 expression and RAS
      status may be the prognostic indicators for mCRC patients with palliative
      operation.

PMID- 29662890
TI  - Harsh Working Conditions and Poor Eating Habits: Health-Related Concerns of
      Female Head Porters (Kayayei) in the Mallam Atta Market, Accra, Ghana.
AB  - Background: The kaya business is known to pose significant health-related risks
      to female migrants. This study sought to explore the health-related concerns of
      female head porters in the Mallam Atta market, Accra, Ghana. Methods: A
      qualitative study was conducted in which twenty female head porters at the Mallam
      Atta market in Accra were interviewed. A thematic analysis was performed and the
      emerging themes were presented and supported with quotations from the
      respondents. Results: Poor accommodation and eating habits, harsh working
      conditions, and lack of knowledge about health conditions exposed the respondents
      to several health-related concerns like neck pains, skin rashes, malaria,
      cholera, and stomach ache among other infections. The popular means of seeking
      health care was through purchasing drugs from pharmacies or drug peddlers instead
      of health facilities. Financial constraints, lack of faith in the National Health
      Insurance Scheme, and long waiting periods at the health facilities militated
      against seeking appropriate health care at the hospitals and clinics. Conclusion:
      Political willpower needs to be strengthened for poverty reduction strategies
      such as training of hairdressing, dress and soap making, and shea butter
      processing for women from the Northern regions in order to ameliorate their
      livelihoods and/or reduce migration to the south.

PMID- 29662889
TI  - Effect of miR-29b on the Proliferation and Apoptosis of Pulmonary Artery Smooth
      Muscle Cells by Targeting Mcl-1 and CCND2.
AB  - The proliferation and apoptosis of pulmonary artery smooth muscle cells (PASMCs)
      are considered to be key steps in the progression of pulmonary arterial
      hypertension (PAH). MicroRNAs (e.g., miR-29b) have been identified in various
      diseases to be critical modulators of cell growth and apoptosis by targeting Mcl
      1 and CCND2. However, the role of miR-29b in PAH remains unknown. So we try to
      investigate the effect of miR-29b on Mcl-1 and CCND2 protein in PASMCs, analyze
      the effect of miR-29b on the proliferation of PASMCs, and explore the
      significance of miR-29b in the proliferation, apoptosis, and gene therapy of PAH.
      It was observed that gene chip analysis showed miR-29b expression in pulmonary
      artery tissue. The expression of miR-29b was significantly reduced in PAH model
      mice. MiR-29b inhibited the proliferation of PASMCs and promoted the apoptosis of
      PASMCs. Mechanically, miR-29b could inhibit the expression of Mcl-1 and CCND2
      protein and silenced Mcl-1 and CCND2 could abolish the change of proliferation
      and apoptosis of PASMCs. These results demonstrate that miR-29b suppressed
      cellular proliferation and promoted apoptosis of PASMCs, possibly through the
      inhibition of Mcl-1 and CCND2. Therefore, miR-29b may serve as a useful
      therapeutic tool to treat PAH.

PMID- 29662891
TI  - Transient Abnormalities in Masking Tuning Curve in Early Progressive Hearing Loss
      Mouse Model.
AB  - Damage to cochlear outer hair cells (OHCs) usually affects frequency selectivity
      in proportion to hearing threshold increase. However, the current clinical
      heuristics that attributes poor hearing performance despite near-normal auditory
      sensitivity to auditory neuropathy or "hidden" synaptopathy overlooks possible
      underlying OHC impairment. Here, we document the part played by OHCs in
      influencing suprathreshold auditory performance in the presence of noise in a
      mouse model of progressive hair cell degeneration, the CD1 strain, at postnatal
      day 18-30 stages when high-frequency auditory thresholds remained near-normal.
      Nonetheless, total loss of high-frequency distortion product otoacoustic
      emissions pointed to nonfunctioning basal OHCs. This "discordant profile" came
      with a huge low-frequency shift of masking tuning curves that plot the level of
      interfering sound necessary to mask the response to a probe tone, against
      interfering frequency. Histology revealed intense OHC hair bundle abnormalities
      in the basal cochlea uncharacteristically associated with OHC survival and
      preserved coupling with the tectorial membrane. This pattern dismisses the
      superficial diagnosis of "hidden" neuropathy while underpinning a disorganization
      of cochlear frequency mapping with optimistic high-frequency auditory thresholds
      perhaps because responses to high frequencies are apically shifted. The
      audiometric advantage of frequency transposition is offset by enhanced masking by
      low-frequency sounds, a finding essential for guiding rehabilitation.

PMID- 29662892
TI  - Revealing the Amylase Interactome in Whole Saliva Using Proteomic Approaches.
AB  - Understanding proteins present in saliva and their function when isolated is not
      enough to describe their real role in the mouth. Due to protein-protein
      interactions, structural changes may occur in macromolecules leading to
      functional modulation or modification. Besides amylase's function in carbohydrate
      breakdown, amylase can delay proteolytic degradation of protein partners (e.g.,
      histatin 1) when complexed. Due to its biochemical characteristics and high
      abundance in saliva, amylase probably interacts with several proteins acting as a
      biological carrier. This study focused on identifying interactions between
      amylase and other proteins found in whole saliva (WS) using proteomic approaches.
      Affinity chromatography was used, followed by gel electrophoresis methods, sodium
      dodecyl sulfate and native, tryptic in-solution and in-gel digestion, and mass
      spectrometry. We identified 66 proteins that interact with amylase in WS.
      Characterization of the identified proteins suggests that acidic (pI < 6.8) and
      low molecular weight (MW < 56 kDa) proteins have preference during amylase
      complex formation. Most of the identified proteins present biological functions
      related to host protection. A new protein-amylase network was constructed using
      the STRING database. Further studies are necessary to investigate individualities
      of the identified amylase interactors. These observations open avenues for more
      comprehensive studies on not yet fully characterized biological function of
      amylase.

PMID- 29662893
TI  - Detecting Early Warning Signal of Influenza A Disease Using Sample-Specific
      Dynamical Network Biomarkers.
AB  - Aims/Introduction. Evidences have shown that the deteriorated procession of
      disease is not a smooth change with time and conditions, in which a critical
      transition point denoted as predisease state drives the state from normal to
      disease. Considering individual differences, this paper provides a sample
      specific method that constructs an index with individual-specific dynamical
      network biomarkers (DNB) which are defined as early warning index (EWI) for
      detecting predisease state of individual sample. Based on microarray data of
      influenza A disease, 144 genes are selected as DNB and the 7th time period is
      defined as predisease state. In addition, according to functional analysis of the
      discovered DNB, it is relevant with experience data, which can illustrate the
      effectiveness of our sample-specific method.

PMID- 29662894
TI  - Body Image of Highly Trained Female Athletes Engaged in Different Types of Sport.
AB  - Background: The aim of the study was to evaluate differences in body image across
      different types of sports in highly trained female athletes. Methods: 242 female
      individuals, aged 13-30 years (M = 20.0, SD = 4.5), representing aesthetic sports
      (n = 56) and nonaesthetic sports (n = 186), were recruited from different sports
      clubs in Poland. Body image, BMI, age, the level of competition attained, and the
      training background of participants were recorded. Results: One-way ANOVA showed
      differences in the body image of athletes engaged in different types of sport
      (F(11,230) = 4.10, p < 0.001, and eta2 = 0.16). The model predicting the body
      image of female athletes was significant (F(5,236) = 10.40, p < 0.001); the
      adjusted R2 = 0.163. Type of sport explained 7.1% (beta = -0.263, p < 0.001), age
      explained 4.5% (beta = 0.341, p < 0.001), BMI explained 3.6% (beta = -0.230, p <
      0.001), and level of competition explained 0.9% (beta = 0.153, p < 0.05) of
      variance in body image. Conclusions: The findings provide vital new knowledge
      which can be used by researchers and practitioners in designing educational
      programs on weight-related behaviors in female athletes. Such programs should be
      implemented especially in young female athletes participating in high-level
      sporting activities at an early stage.

PMID- 29662896
TI  - Early Experience with Reduction of Unstable Pelvic Fracture Using a Computer
      Aided Reduction Frame.
AB  - Purpose: The optimal closed reduction technique for unstable pelvic fractures
      remains controversial. The purpose of this study is to verify the effectiveness
      and report early experiences with the reduction of unstable pelvic fractures
      using a computer-aided pelvic reduction frame. Methods: From January 2015 to
      August 2016, a total of 10 patients with unilateral unstable pelvic fractures
      were included in this study. The surgical reduction procedure was based on the
      protocol of the computer-aided pelvic reduction frame that we proposed in a
      previous work. The quality of the reductions achieved using this system was
      evaluated with residual translational and rotational differences between the
      actual and virtual reduction positions of pelvis. The duration of the operation
      was recorded for quality control. Results: The mean times required to set up the
      frame, to complete the virtual surgery simulation, and to reduce the unstable
      pelvic fractures were 10.3, 20.9, and 7.5 min, respectively. The maximum residual
      translational and rotational displacements were less than 6.5 mm and 3.71
      degrees, respectively. Conclusions: This computer-aided reduction frame can be a
      useful tool for the speedy and accurate reduction of unstable pelvic fractures.
      Further clinical studies should be conducted with larger patient samples to
      verify its safety and efficacy.

PMID- 29662895
TI  - Heme Oxygenase-1 Activity as a Correlate to Exercise-Mediated Amelioration of
      Cognitive Decline and Neuropathological Alterations in an Aging Rat Model of
      Dementia.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder with cognitive
      impairment. Physical exercise has long been proven to be beneficial in the
      disorder. The present study was designed to examine the effect of voluntary
      exercise on spatial memory, imaging, and pathological abnormalities. Particular
      focus has been given to the role of heme oxygenase-1 (HO-1)-an important cellular
      cytoprotectant in preserving mental acuity-using an aging rat model of dementia.
      Male and female Wistar rats were segregated into six groups-namely, (i) aged
      sedentary (control) females (ASF, n = 8); (ii) aged sedentary (control) males
      (ASM, n = 8); (iii) aged running females (ARF, n = 8); (iv) aged running males
      (ARM, n = 8); (v) young control females (YCF, n = 8); and (vi) young control
      males (YCM, n = 8). Rats in the ARF and ARM groups had free access to a
      standardized inbuilt running wheel during the 3-month evaluation period. Spatial
      memory was investigated using the Morris Water Test, imaging and pathological
      alterations were assessed using positron emission tomography (PET) imaging and
      histopathological examinations (H&E, Congo red staining), respectively, and HO-1
      enzyme activity assays were also conducted. The outcomes suggest that voluntary
      physical exercise mitigates impaired spatial memory and neuropathological changes
      exhibited by the aging sedentary group, via elevated HO-1 activity, contributing
      to the antioxidant capacity in the aging brain.

PMID- 29662897
TI  - Novel Compliant Scaffold with Specific Design for Venous System: Results of a
      Porcine Model Study.
AB  - Background: Stenting has become the first-line treatment of obstructive venous
      disease because of poor results of balloon angioplasty. This preclinical study
      aimed to investigate the safety and efficacy profile of a novel compliant venous
      scaffold (CVS) denominated Petalo CVS, specifically designed for venous diseases.
      Materials and Methods: Twelve healthy pigs weighing 90 kg were used to test
      Petalo CVS. The devices were implanted into the internal jugular veins (IJVs)
      using a femoral vein percutaneous approach. The safety profile including the
      success rate of device releasing, anchoring, and positioning was evaluated
      immediately. Fracture, migration, primary patency, and endothelial response were
      assessed at 1, 2, 3, and 6 months after the study procedure. Results: A total of
      32 devices were successfully released in both IJVs. No procedure- or device
      related complications were reported, and all pigs successfully completed the
      different scheduled follow-up periods. The primary patency rate was 100%, and no
      fracture or migration of the device into the brachiocephalic trunk was reported.
      Histological examination revealed only minimal lesions with minimal or absent
      inflammatory reaction surrounding the incorporated metallic rods. Conclusions:
      This porcine model study showed a promising safety and efficacy profile of Petalo
      CVS, a novel endovenous device based on specific concepts.

PMID- 29662898
TI  - Comparing Different Recording Lengths of Dynamic Cerebral Autoregulation: 5
      versus 10 Minutes.
AB  - We compared the dynamic cerebral autoregulation (dCA) indices between 5- and 10
      minute data lengths by analyzing 37 patients with ischemic stroke and 51 controls
      in this study. Correlation coefficient (Mx) and transfer function analysis were
      applied for dCA analysis. Mx and phase shift in all frequency bands were not
      significantly different between 5- and 10-minute recordings [mean difference: Mx
      = 0.02; phase shift of very low frequency (0.02-0.07 Hz) = 0.3 degrees , low
      frequency (0.07-0.20 Hz) = 0.6 degrees , and high frequency (0.20-0.50 Hz) = 0.1
      degrees ]. However, the gains in all frequency bands of a 5-minute recording were
      slightly but significantly higher than those of a 10-minute recording (mean
      difference of gain: very low frequency = 0.05 cm/s/mmHg, low frequency = 0.11
      cm/s/mmHg, and high frequency = 0.14 cm/s/mmHg). The intraclass correlation
      coefficients between all dCA indices of 5- and 10-minute recordings were
      favorable, especially in Mx (0.93), phase shift in very low frequency (0.87), and
      gain in very low frequency (0.94). The areas under the receiver operating
      characteristic curve for stroke diagnosis between 5- and 10-minute recordings
      were not different. We concluded that dCA assessed by using a 5-minute recording
      is not significantly different from that using a 10-minute recording in the
      clinical application.

PMID- 29662899
TI  - Chromium(VI) Toxicity in Legume Plants: Modulation Effects of Rhizobial
      Symbiosis.
AB  - Most legume species have the ability to establish a symbiotic relationship with
      soil nitrogen-fixing rhizobacteria that promote plant growth and productivity.
      There is an increasing evidence of reactive oxygen species (ROS) important role
      in formation of legume-rhizobium symbiosis and nodule functioning. Environmental
      pollutants such as chromium compounds can cause damage to rhizobia, legumes, and
      their symbiosis. In plants, toxic effects of chromium(VI) compounds are
      associated with the increased production of ROS and oxidative stress development
      as well as with inhibition of pigment synthesis and modification of virtually all
      cellular components. These metabolic changes result in inhibition of seed
      germination and seedling development as well as reduction of plant biomass and
      crop yield. However, if plants establish symbiosis with rhizobia, heavy metals
      are accumulated preferentially in nodules decreasing the toxicity of metals to
      the host plant. This review summarizes data on toxic effects of chromium on
      legume plants and legume-rhizobium symbiosis. In addition, we discussed the role
      of oxidative stress in both chromium toxicity and formation of rhizobial
      symbiosis and use of nodule bacteria for minimizing toxic effects of chromium on
      plants.

PMID- 29662900
TI  - Analysis of the Clinicopathological Characteristics and Risk Factors in Patients
      with Lung Cancer and Chronic Obstructive Pulmonary Disease.
AB  - Objective: To investigate the clinicopathological characteristics and risk
      factors in patients with lung cancer and COPD. Materials and Methods: We
      retrospectively reviewed the clinical data of 282 patients with lung cancer,
      including 174 and 108 patients with and without COPD, respectively. Information
      on age, sex, smoking status, and histologic type was obtained from medical
      records. Results: Lung cancer patients with COPD and those with the chronic
      bronchitis (CB) phenotype had higher smoking indices compared to those without
      COPD (723.95 +/- 631.48 and 920.95 +/- 712.93 versus 418.40 +/- 506.84; P =
      0.010; P = 0.001, resp.), and current smokers accounted for significantly higher
      proportions of lung cancer patients with COPD and the CB phenotype versus without
      COPD (51.15% and 63.74% versus 35.19%; P = 0.009; P = 0.001, resp.).
      Adenocarcinoma was significantly more common in lung cancer patients without
      versus with COPD (48.15% versus 35.63%; P = 0.037), whereas small cell lung
      cancer was more common in patients with COPD (23.56% versus 13.89%). Among
      patients with COPD, male sex (odds ratio [OR], 19.946; P < 0.001), current
      smokers (OR: 6.588; P = 0.001), and age >= 75 years (OR: 2.670; P = 0.008) were
      identified as high-risk factors. Conclusion: The risk factors for COPD among lung
      cancer patients were age >= 75 years, current smokers with the CB phenotype, and
      male sex.

PMID- 29662901
TI  - How to Apply Feedback to Improve Subjective Wellbeing of Government Servants
      Engaged in Environmental Protection in China?
AB  - Background: In order to improve subjective wellbeing of government servants
      engaged in environmental protection who work in high power distance in China, it
      is important to understand the impact mechanism of feedback. This study aims to
      analyze how feedback environment influences subjective wellbeing through basic
      psychological needs satisfaction and analyzing the moderating role of power
      distance. Method: The study was designed as a cross-sectional study of 492
      government servants engaged in environment protection in Shandong, China.
      Government servants who agreed to participate answered self-report questionnaires
      concerning demographic conditions, supervisor feedback environment, basic
      psychological need satisfaction, and power distance as well as subjective
      wellbeing. Results: Employees in higher levels of supervisor feedback environment
      were more likely to experience subjective wellbeing. Full mediating effects were
      found for basic psychological needs satisfaction. Specifically, supervisor
      feedback environment firstly led to increased basic psychological needs
      satisfaction, which in turn resulted in increased subjective wellbeing.
      Additional analysis showed that the mediating effect of basic psychological needs
      satisfaction was stronger for employees who work in high power distance than in
      low power distance. Conclusion: The results from the study indicate that
      supervisor feedback environment plays a vital role in improving subjective
      wellbeing of government servants engaged in environmental protection through
      basic psychological needs satisfaction, especially in high power distance.

PMID- 29662903
TI  - The Effect of an Authentic Acute Physical Education Session of Dance on
      Elementary Students' Selective Attention.
AB  - There have been calls to test the potential benefits of different forms of
      physical activity (PA) to executive function, particularly in authentic settings.
      Hence, the purpose of this study was to investigate the effect of an acute dance
      session within an existing physical education class on students' selective
      attention. The study employed a pre/posttest quasi-experimental design with a
      comparison group in one Aotearoa, New Zealand, primary school. Participants were
      192 students (comparison group = 104 students) in Years 5 and 6. The intervention
      group participated in a dance-based physical education lesson while the
      comparison group continued their regular classroom work. PA during the physical
      education lesson was monitored using accelerometers. Selective attention was
      assessed at pretest and after the comparison/physical education sessions with the
      d2 Test of Attention. 2 * 2 ANOVA results suggested a significant time effect for
      all three measures, no significant group effects for any measures, and
      significant time by group interactions for TN and CP but not for E%. The
      intervention group improved significantly more than the comparison group for TN
      and CP. This study's findings suggest that existing school opportunities focused
      on cognitively engaging PA, such as dance, can improve aspects of students'
      selective attention.

PMID- 29662902
TI  - Isolation of Extracellular Vesicles: General Methodologies and Latest Trends.
AB  - Background: Extracellular vesicles (EVs) play an essential role in the
      communication between cells and transport of diagnostically significant
      molecules. A wide diversity of approaches utilizing different biochemical
      properties of EVs and a lack of accepted protocols make data interpretation very
      challenging. Scope of Review: This review consolidates the data on the classical
      and state-of-the-art methods for isolation of EVs, including exosomes,
      highlighting the advantages and disadvantages of each method. Various
      characteristics of individual methods, including isolation efficiency, EV yield,
      properties of isolated EVs, and labor consumption are compared. Major
      Conclusions: A mixed population of vesicles is obtained in most studies of EVs
      for all used isolation methods. The properties of an analyzed sample should be
      taken into account when planning an experiment aimed at studying and using these
      vesicles. The problem of adequate EVs isolation methods still remains; it might
      not be possible to develop a universal EV isolation method but the available
      protocols can be used towards solving particular types of problems. General
      Significance: With the wide use of EVs for diagnosis and therapy of various
      diseases the evaluation of existing methods for EV isolation is one of the key
      problems in modern biology and medicine.

PMID- 29662904
TI  - Identification of Differentially Expressed Genes in Porcine Ovaries at Proestrus
      and Estrus Stages Using RNA-Seq Technique.
AB  - Estrus is an important factor for the fecundity of sows, and it is involved in
      ovulation and hormone secretion in ovaries. To better understand the molecular
      mechanisms of porcine estrus, the expression patterns of ovarian mRNA at
      proestrus and estrus stages were analyzed using RNA sequencing technology. A
      total of 2,167 differentially expressed genes (DEGs) were identified (P <= 0.05,
      |log2  Ratio| >= 1), of which 784 were upregulated and 1,383 were downregulated
      in the estrus compared with the proestrus group. Gene Ontology (GO) enrichment
      indicated that these DEGs were mainly involved in the cellular process, single
      organism process, cell and cell part, and binding and metabolic process. In
      addition, a pathway analysis showed that these DEGs were significantly enriched
      in 33 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, including cell
      adhesion molecules, ECM-receptor interaction, and cytokine-cytokine receptor
      interaction. Quantitative real-time reverse transcription polymerase chain
      reaction (qRT-PCR) confirmed the differential expression of 10 selected DEGs.
      Many of the novel candidate genes identified in this study will be valuable for
      understanding the molecular mechanisms of the sow estrous cycle.

PMID- 29662905
TI  - Systemic Infection of Nicotiana benthamiana with Potato virus X Nanoparticles
      Presenting a Fluorescent iLOV Polypeptide Fused Directly to the Coat Protein.
AB  - Plant virus-based nanoparticles can be produced in plants on a large scale and
      are easily modified to introduce new functions, making them suitable for
      applications such as vaccination and drug delivery, tissue engineering, and in
      vivo imaging. The latter is often achieved using green fluorescent protein and
      its derivatives, but the monovalent fluorescent protein iLOV is smaller and more
      robust. Here, we fused the iLOV polypeptide to the N-terminus of the Potato virus
      X (PVX) coat protein, directly or via the Foot-and-mouth disease virus 2A
      sequence, for expression in Nicotiana benthamiana. Direct fusion of the iLOV
      polypeptide did not prevent the assembly or systemic spread of the virus and we
      verified the presence of fusion proteins and iLOV hybrid virus particles in leaf
      extracts. Compared to wild-type PVX virions, the PVX particles displaying the
      iLOV peptide showed an atypical, intertwined morphology. Our results confirm that
      a direct fusion of the iLOV fluorescent protein to filamentous PVX nanoparticles
      offers a promising tool for imaging applications.

PMID- 29662906
TI  - Quantitative Relationships between Pulmonary Function and Residual Neuromuscular
      Blockade.
AB  - Background: Neuromuscular blockade is a risk factor for postoperative respiratory
      weakness during the immediate postoperative period. The quantitative
      relationships between postoperative pulmonary-function impairment and residual
      neuromuscular blockade are unknown. Methods: 113 patients who underwent elective
      laparoscopic cholecystectomy were enrolled in this study. They all had a
      pulmonary-function test (PFT) during the preoperative evaluation. Predictive
      values based on demographic data were also recorded. The train-of-four ratio
      (TOFR) was recorded at the same time as the PFT and at every 5 minutes in the
      qualified 98 patients in the postanesthesia care unit (PACU). We analyzed the
      degree of PFT recovery when the TOFR had recovered to different degrees. Results:
      There was a significant difference (P < 0.05) between the preoperative baseline
      value and the postoperative forced vital capacity at each TOFR point, except at a
      TOFR value of 1.1. There was also a significant difference (P < 0.05) between the
      preoperative baseline value and the postoperative peak expiratory flow at each
      TOFR point. Conclusions: Postoperative residual neuromuscular blockade was common
      (75.51%) after tracheal extubation, and pulmonary function could not recover to
      an acceptable level (85% of baseline value), even if TOFR had recovered to 0.90.
      Trial Registration: Chinese Clinical Trial Register is ChiCTR-OOC-15005838.

PMID- 29662907
TI  - Demystifying MR Neurography of the Lumbosacral Plexus: From Protocols to
      Pathologies.
AB  - Magnetic resonance neurography is a high-resolution imaging technique that allows
      evaluating different neurological pathologies in correlation to clinical and the
      electrophysiological data. The aim of this article is to present a review on the
      anatomy of the lumbosacral plexus nerves, along with imaging protocols,
      interpretation pitfalls, and most common pathologies that should be recognized by
      the radiologist: traumatic, iatrogenic, entrapment, tumoral, infectious, and
      inflammatory conditions. An extensive series of clinical and imaging cases is
      presented to illustrate key-points throughout the article.

PMID- 29662908
TI  - Portable Brain-Computer Interface for the Intensive Care Unit Patient
      Communication Using Subject-Dependent SSVEP Identification.
AB  - A major predicament for Intensive Care Unit (ICU) patients is inconsistent and
      ineffective communication means. Patients rated most communication sessions as
      difficult and unsuccessful. This, in turn, can cause distress, unrecognized pain,
      anxiety, and fear. As such, we designed a portable BCI system for ICU
      communications (BCI4ICU) optimized to operate effectively in an ICU environment.
      The system utilizes a wearable EEG cap coupled with an Android app designed on a
      mobile device that serves as visual stimuli and data processing module.
      Furthermore, to overcome the challenges that BCI systems face today in real-world
      scenarios, we propose a novel subject-specific Gaussian Mixture Model- (GMM-)
      based training and adaptation algorithm. First, we incorporate subject-specific
      information in the training phase of the SSVEP identification model using GMM
      based training and adaptation. We evaluate subject-specific models against other
      subjects. Subsequently, from the GMM discriminative scores, we generate the
      transformed vectors, which are passed to our predictive model. Finally, the
      adapted mixture mean scores of the subject-specific GMMs are utilized to generate
      the high-dimensional supervectors. Our experimental results demonstrate that the
      proposed system achieved 98.7% average identification accuracy, which is
      promising in order to provide effective and consistent communication for patients
      in the intensive care.

PMID- 29662909
TI  - Development and Validation of a Short Version of the Anterior Cruciate Ligament
      Return to Sport After Injury (ACL-RSI) Scale.
AB  - Background: The Anterior Cruciate Ligament Return to Sport After Injury (ACL-RSI)
      scale was developed to measure an athlete's psychological readiness to return to
      sport after anterior cruciate ligament (ACL) injury and reconstruction surgery.
      The scale is being used with increasing frequency in both research and clinical
      settings. Purpose: To generate and validate a short version of the ACL-RSI scale.
      Study Design: Cohort study (diagnosis); Level of evidence, 2. Methods: The ACL
      RSI scale was administered to 535 patients who had undergone ACL reconstruction
      surgery. Reliability (Cronbach alpha) was determined and factor analysis of the
      full scale was undertaken along with a process of item selection and elimination.
      A second group of 250 patients participated in a predictive validation analysis.
      This group completed the ACL-RSI scale at 6 months and reported return-to-sport
      outcomes 12 months following ACL reconstruction surgery. The predictive validity
      of both scales (full and short versions) was assessed by use of receiver
      operating characteristic (ROC) curve statistics. Results: The scale was found to
      have high internal consistency (Cronbach alpha, 0.96), which suggested that item
      redundancy was present. After an item selection process, the scale was reduced to
      a 6-item format. Cronbach alpha for the short version was 0.92, and factor
      analysis confirmed the presence of 1 factor accounting for 71% of the total
      variance. Scores for the short version were significantly different between
      patients who had and those who had not returned to sport. Six-month ACL-RSI
      scores for both the full and short versions had fair to good predictive ability
      for 12-month return-to-sport outcomes (full version: area under ROC curve, 0.77
      [95% CI, 0.7-0.8]; short version: area under ROC curve, 0.75 [95% CI, 0.7-0.8]).
      Conclusion: A 6-item short version of the ACL-RSI scale was developed from a
      large cohort of patients undergoing ACL reconstruction. The short version appears
      to be as robust as the full version for discriminating between and predicting
      return-to-sport outcomes. The short version of the ACL-RSI may be of use in busy
      clinical settings to help identify athletes who may find return to sport
      challenging.

PMID- 29662910
TI  - Outcomes and Return to Sport After Revision Anterior Cruciate Ligament
      Reconstruction in Adolescent Athletes.
AB  - Background: The number of adolescent anterior cruciate ligament (ACL) injuries is
      rising with increased participation in higher level athletics at earlier ages.
      With an increasing number of primary ACL reconstructions (ACLRs) comes a rise in
      the incidence of revision ACLRs. Purpose: To evaluate the clinical results of
      revision ACLR across a group of high-level adolescent athletes with at least 2
      year follow-up. Study Design: Case series; Level of evidence, 4. Methods: A
      retrospective review of 21 adolescent athletes (age range, 10-19 years) who
      underwent revision ACLR with at least 2-year follow-up was conducted. Patient
      reported outcome measures (PROMs) included the International Knee Documentation
      Committee (IKDC) Subjective Knee Evaluation Form, Lysholm knee scoring scale,
      Tegner activity level scale, and modified Cincinnati Knee Rating System. Return
      to sport (RTS) and overall patient satisfaction were also assessed. Results: The
      mean age at the time of surgery was 16.5 years (range, 14-19 years), and the mean
      follow-up was 46.4 months (range, 24-97 months); 42.9% of patients were female,
      and 52.4% of patients participated in collision sports. The mean time to failure
      after primary ACLR was 13.1 +/- 8.0 months, and the most common mechanism of
      failure was noncontact in at least 66.7% of cases. The revision graft type
      included bone-patellar tendon-bone (BPTB) in 71.4% of cases; 26.7% of BPTB grafts
      were from the contralateral extremity. Concomitant procedures were performed for
      intra-articular lesions in 71.4% of patients. The mean patient satisfaction rate
      was 95.3%. There were 3 cases of a graft reinjury at a mean of 25 months
      postoperatively. The mean PROM scores were as follows: IKDC, 87.5 +/- 12.7;
      Tegner, 7.2 +/- 2.0; Lysholm, 93.7 +/- 9.8; and Cincinnati, 93.4 +/- 10.0. Of
      those attempting to RTS, 68.4% of patients successfully returned at the same
      level of competition. Patients with a lateral compartment chondral injury were
      less likely to RTS (P < .05). Independent variables shown to have no significant
      relationship to PROMs or RTS included age, follow-up, sport classification,
      associated meniscal tears, revision graft size/type, and concomitant procedures.
      Conclusion: Revision ACLR can be an effective surgical option in adolescents
      participating in collision and contact sports, with good to excellent subjective
      outcome scores. At a minimum 2-year follow-up, a graft rupture after revision
      ACLR occurred in 14% of cases. Of the athletes attempting to RTS, 68.4% returned
      to their preinjury level of competition.

PMID- 29662911
TI  - Unaccounted Workload Factor: Game-Day Pitch Counts in High School Baseball
      Pitchers-An Observational Study.
AB  - Background: Throwing injuries are common in high school baseball. Known risk
      factors include excessive pitch counts, year-round pitching, and pitching with
      arm pain and fatigue. Despite the evidence, the prevalence of pitching injuries
      among high school players has not decreased. One possibility to explain this
      pattern is that players accumulate unaccounted pitch volume during warm-up and
      bullpen activity, but this has not yet been examined. Hypotheses: Our primary
      hypothesis was that approximately 30% to 40% of pitches thrown off a mound by
      high school pitchers during a game-day outing are unaccounted for in current data
      but will be revealed when bullpen sessions and warm-up pitches are included. Our
      secondary hypothesis was that there is wide variability among players in the
      number of bullpen pitches thrown per outing. Study Design: Cross-sectional study;
      Level of evidence, 3. Methods: Researchers counted all pitches thrown off a mound
      during varsity high school baseball games played by 34 high schools in North
      Central Florida during the 2017 season. Results: We recorded 13,769 total pitches
      during 115 varsity high school baseball starting pitcher outings. The mean +/- SD
      pitch numbers per game were calculated for bullpen activity (27.2 +/- 9.4), warm
      up (23.6 +/-8.0), live games (68.9 +/-19.7), and total pitches per game (119.7 +/
      27.8). Thus, 42.4% of the pitches performed were not accounted for in the pitch
      count monitoring of these players. The number of bullpen pitches thrown varied
      widely among players, with 25% of participants in our data set throwing fewer
      than 22 pitches and 25% throwing more than 33 pitches per outing. Conclusion: In
      high school baseball players, pitch count monitoring does not account for the
      substantial volume of pitching that occurs during warm-up and bullpen activity
      during the playing season. These extra pitches should be closely monitored to
      help mitigate the risk of overuse injury.

PMID- 29662912
TI  - Relationship Between Quantitative MRI Biomarkers and Patient-Reported Outcome
      Measures After Cartilage Repair Surgery: A Systematic Review.
AB  - Background: Treatment of articular cartilage injuries remains a clinical
      challenge, and the optimal tools to monitor and predict clinical outcomes are
      unclear. Quantitative magnetic resonance imaging (qMRI) allows for a noninvasive
      biochemical evaluation of cartilage and may offer advantages in monitoring
      outcomes after cartilage repair surgery. Hypothesis: qMRI sequences will
      correlate with early pain and functional measures. Study Design: Systematic
      review; Level of evidence, 3. Methods: A PubMed search was performed with the
      following search terms: knee AND (cartilage repair OR cartilage restoration OR
      cartilage surgery) AND (delayed gadolinium-enhanced MRI OR t1-rho OR T2 mapping
      OR dgemric OR sodium imaging OR quantitative imaging). Studies were included if
      correlation data were included on quantitative imaging results and patient
      outcome scores. Results: Fourteen articles were included in the analysis. Eight
      studies showed a significant relationship between quantitative cartilage imaging
      and patient outcome scores, while 6 showed no relationship. T2 mapping was
      examined in 11 studies, delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) in
      4 studies, sodium imaging in 2 studies, glycosaminoglycan chemical exchange
      saturation transfer (gagCEST) in 1 study, and diffusion-weighted imaging in 1
      study. Five studies on T2 mapping showed a correlation between T2 relaxation
      times and clinical outcome scores. Two dGEMRIC studies found a correlation
      between T1 relaxation times and clinical outcome scores. Conclusion: Multiple
      studies on T2 mapping, dGEMRIC, and diffusion-weighted imaging showed significant
      correlations with patient-reported outcome measures after cartilage repair
      surgery, although other studies showed no significant relationship. qMRI
      sequences may offer a noninvasive method to monitor cartilage repair tissue in a
      clinically meaningful way, but further refinements in imaging protocols and
      clinical interpretation are necessary to improve utility.

PMID- 29662913
TI  - High Rate of Missed Lateral Meniscus Posterior Root Tears on Preoperative
      Magnetic Resonance Imaging.
AB  - Background: Lateral meniscus posterior root tears (LMPRTs), if left untreated,
      can cause devastating effects to the knee, with rapid articular cartilage
      degeneration and loss of the meniscus as a secondary stabilizer. Detection and
      surgical repair of these defects have been linked to favorable outcomes, but
      preoperative identification of LMPRTs continues to be challenging. Purpose: To
      determine the rate of LMPRTs diagnosed preoperatively on magnetic resonance
      imaging (MRI) in a consecutive series of arthroscopically confirmed LMPRTs. Study
      Design: Case series; Level of evidence, 4. Methods: A retrospective cohort of 45
      consecutive patients with arthroscopically confirmed LMPRTs between 2010 and 2017
      were included in this study. The preoperative MRI report for each patient was
      evaluated and compared with intraoperative findings. Each preoperative MRI study
      was then reviewed by 2 fellowship-trained musculoskeletal radiologists who worked
      in consensus. Results: A total of 45 patients (32 males, 13 females) with
      arthroscopically confirmed LMPRTs and a mean age of 27 years (range, 14-54 years)
      were included in the study. Only 15 of 45 LMPRTs (33%) were initially diagnosed
      on preoperative MRI. Past or concurrent anterior cruciate ligament (ACL)
      reconstruction was present in 37 of 45 cases (82%). Upon retrospective review, 15
      of the 30 missed LMPRTs were "clearly evident," 12 "subtly evident," and 3
      "occult" (unavoidably missed). There were no significant differences in the rate
      of LMPRT diagnosis based on history of prior knee surgery, meniscus extrusion, or
      tearing of the meniscofemoral ligament. Conclusion: Despite improved
      identification of other meniscus tear patterns on MRI, a high percentage of
      LMPRTs were still missed. In the setting of previous ACL reconstruction, if the
      root cannot be confidently identified, the MRI interpretation should indicate
      that "the root is poorly visualized" to alert the surgeon to thoroughly evaluate
      this structure. The surgeon should maintain a high index of suspicion and
      carefully probe the posterior root of the lateral meniscus at the time of
      arthroscopy, especially in cases of ACL injury.

PMID- 29662914
TI  - Ligament Strain Response Between Lower Extremity Contralateral Pairs During In
      Vitro Landing Simulation.
AB  - Background: Limb asymmetries, as determined through in vivo biomechanical
      measures, are known risk factors for anterior cruciate ligament (ACL) injury.
      Previous cadaveric studies have shown a lack of significant differences in
      ligament strain between contralateral lower extremities when identical kinematics
      were simulated on specimens. Recent methodological developments have applied in
      vivo knee kinetics to exert landing forces on cadaveric lower extremities to
      mimic ACL injury events, but it is unknown whether contralateral limbs fail in a
      consistent manner during impact simulator testing. Hypothesis: It was
      hypothesized that contralateral lower extremities would not exhibit side-to-side
      differences in ligament strains. Furthermore, it was hypothesized that failure
      loads and failure locations would be independent of limb dominance. Study Design:
      Controlled laboratory study. Methods: Fourteen pairs of cadaveric lower
      extremities were obtained from an anatomic donations program (8 female, 6 male;
      mean +/- SD: age, 41.7 +/- 8.1 years; mass, 86.8 +/- 27.0 kg; body mass index,
      29.4 +/- 9.0 kg/m2). A mechanical impact simulator was used to re-create the
      impulse ground-reaction force generated during an in vivo landing task. Ligament
      strains were recorded by differential variable force transducers implanted on the
      ACL and medial collateral ligament (MCL). Results: No significant differences
      were observed in peak ACL or peak MCL strain for 5 loading conditions. Fisher
      exact tests of independence revealed that limb dominance was independent of both
      load at failure and failure location. Conclusion: There were no significant
      differences in ACL and MCL strain values between limb sides during in vitro
      impact simulation testing. This finding indicates that limb dominance does not
      influence the failure threshold of the ACL, since there was no significant
      difference in failure strains. The functional mechanics of the ACL are comparable
      between contralateral pairs from the same healthy specimen. Clinical Relevance:
      Injury mechanisms and intra-articular mechanics cannot be ethically studied in an
      in vivo setting. The current study provides additional insight into limb
      asymmetry that is observed among athletes in clinical sports medicine settings.

PMID- 29662915
TI  - Patient Perspectives of Midlevel Providers in Orthopaedic Sports Medicine.
AB  - Background: Midlevel providers (eg, nurse practitioners and physician assistants)
      have been integrated into orthopaedic systems of care in response to the
      increasing demand for musculoskeletal care. Few studies have examined patient
      perspectives toward midlevel providers in orthopaedic sports medicine. Purpose:
      To identify perspectives of orthopaedic sports medicine patients regarding
      midlevel providers, including optimal scope of practice, reimbursement equity
      with physicians, and importance of the physician's midlevel provider to patients
      when initially selecting a physician. Study Design: Cross-sectional study; Level
      of evidence, 3. Methods: A total of 690 consecutive new patients of 3 orthopaedic
      sports medicine physicians were prospectively administered an anonymous
      questionnaire prior to their first visit. Content included patient perspectives
      regarding midlevel provider importance in physician selection, optimal scope of
      practice, and reimbursement equity with physicians. Results: Of the 690
      consecutive patients who were administered the survey, 605 (87.7%) responded. Of
      these, 51.9% were men and 48.1% were women, with a mean age of 40.5 +/- 15.7
      years. More than half (51.2%) perceived no differences in training levels between
      physician assistants and nurse practitioners. A majority of patients (62.9%)
      reported that the physician's midlevel provider is an important consideration
      when choosing a new orthopaedic sports medicine physician. Patients had specific
      preferences regarding which services should be physician provided. Patients also
      reported specific preferences regarding those services that could be midlevel
      provided. There lacked a consensus on reimbursement equity for midlevel
      practitioners and physicians, despite 71.7% of patients responding that the
      physician provides a higher-quality consultation. Conclusion: As health care
      becomes value driven and consumer-centric, understanding patient perspectives on
      midlevel providers will allow orthopaedic sports medicine physicians to optimize
      efficiency and patient satisfaction. Physicians may consider these data in
      clinical workforce planning, as patients preferred specific services to be
      physician or midlevel provided. It may be worthwhile to consider midlevel
      providers in marketing efforts, given that patients considered the credentials of
      the physician's midlevel provider when initially selecting a new physician.
      Patients lacked consensus regarding reimbursement equity between physicians and
      midlevel providers, despite responding that the physician provides a higher
      quality consultation. Our findings are important for understanding the midlevel
      workforce as it continues to grow in response to the increasing demand for
      orthopaedic sports care.

PMID- 29662916
TI  - Intracranial Hemorrhage and Autoimmune Thrombocytopenia in a Neonate: A Rare
      "Unpredictable" Event.
AB  - Neonatal thrombocytopenia is a rare complication of maternal autoimmune
      thrombocytopenia, and no maternal predictors of its gravity and potential
      complications have been identified. Neonatal cerebral hemorrhage, a feared event
      in the setting of autoimmune thrombocytopenia, is fortunately uncommon, but it
      can occur in utero or in the perinatal period, with potentially serious
      consequences. The authors report the case of a boy born to a mother affected by
      autoimmune thrombocytopenia, who presented with severe thrombocytopenia at birth
      and developed intracranial hemorrhage despite mild maternal thrombocytopenia at
      delivery and a prompt preventive treatment of the newborn. Platelet count should
      be tested at birth in all babies born from mothers with autoimmune
      thrombocytopenia, irrespective of maternal platelets counts during pregnancy or
      at delivery, and should be closely monitored during the first days of life.
      Systematic early and serial cranial ultrasound might be advocated in the setting
      of neonatal thrombocytopenia.

PMID- 29662917
TI  - Special Section Guest Editorial: Functional Near Infrared Spectroscopy, Part 3.
AB  - A guest editorial to summarize the Special Section on Functional Near Infrared
      Spectroscopy.

PMID- 29662918
TI  - GIFTed Demons: deformable image registration with local structure-preserving
      regularization using supervoxels for liver applications.
AB  - Deformable image registration, a key component of motion correction in medical
      imaging, needs to be efficient and provides plausible spatial transformations
      that reliably approximate biological aspects of complex human organ motion.
      Standard approaches, such as Demons registration, mostly use Gaussian
      regularization for organ motion, which, though computationally efficient, rule
      out their application to intrinsically more complex organ motions, such as
      sliding interfaces. We propose regularization of motion based on supervoxels,
      which provides an integrated discontinuity preserving prior for motions, such as
      sliding. More precisely, we replace Gaussian smoothing by fast, structure
      preserving, guided filtering to provide efficient, locally adaptive
      regularization of the estimated displacement field. We illustrate the approach by
      applying it to estimate sliding motions at lung and liver interfaces on
      challenging four-dimensional computed tomography (CT) and dynamic contrast
      enhanced magnetic resonance imaging datasets. The results show that guided filter
      based regularization improves the accuracy of lung and liver motion correction as
      compared to Gaussian smoothing. Furthermore, our framework achieves state-of-the
      art results on a publicly available CT liver dataset.

PMID- 29662919
TI  - Development and clinical validation of a hybrid method for semiautomated left
      ventricle endocardial and epicardial boundary extraction on cine-magnetic
      resonance images.
AB  - We describe a hybrid method for left ventricle (LV) endocardial and epicardial
      segmentation on cardiac magnetic resonance (CMR) images requiring minimal
      operator intervention. Endocardium extraction results from the union of three
      independent estimations based on adaptive thresholding, region growing, and
      active contour with Chan-Vese energy function. Epicardium segmentation relies on
      conditional morphological dilation of the endocardial mask followed by active
      contour optimization. The proposed method was first evaluated using an open
      access database of 18 CMR for which expert manual contouring was available. The
      method was further validated on a retrospective cohort of 29 patients, who
      underwent CMR with expert manual segmentation. Regarding the open access
      database, similarity (Dice index) between hybrid and expert segmentations was
      good for end-diastolic (ED) endocardium (0.92), end-systolic (ES) endocardium
      (0.88), and ED epicardium (0.92). As for derived LV parameters, concordance
      (Lin's coefficient) was good for ED volume (0.91), ES volume (0.93), ejection
      fraction (EF; 0.89), and fair for myocardial mass (MM; 0.74). Regarding the
      retrospective patient study, concordance between expert and hybrid estimations
      was excellent for ED volume (0.95), ES volume (0.96), good for EF (0.86), and
      fair for MM (0.71). Hybrid segmentation resulted in small biases ([Formula: see
      text] for ED volume, [Formula: see text] for ES volume, [Formula: see text] for
      EF, and [Formula: see text] for MM) with little clinical relevance and acceptable
      for routine practice. The quickness and robustness of the proposed hybrid method
      and its ability to provide LV volumes, functions, and masses highly concordant
      with those given by expert segmentation support its pertinence for routine
      clinical use.

PMID- 29662920
TI  - Assessing CT acquisition parameters with visual-search model observers.
AB  - A principal difference between the channelized Hotelling (CH) and visual-search
      (VS) model observers is how they respond to noise texture in images. We compared
      the two observers in lesion-detection studies to evaluate linear and angular
      sampling parameters for CT. Simulated lung images were generated from a single
      two-dimensional mathematical torso phantom containing circular lesions of fixed
      radius and relative contrast. Projection datasets were produced for two detector
      pixel sizes and from 15 to 128 projections at 15 and 65 M counts per set.
      Filtered backprojection reconstructions were obtained with dimensions of
      [Formula: see text] and [Formula: see text]. A localization receiver operating
      characteristic study was conducted with two human observers, three single-feature
      VS observers, and a feature-adaptive VS observer. The effects of the sampling
      parameters on performance were similar for all of these observers. The CH
      observer, applied in location-known studies with and without background
      variability, was not affected by the variations in angular sampling. The two
      stage VS framework was an effective modification of the CH observer for assessing
      the effects of noise texture on human-observer performance in this study.

PMID- 29662922
TI  - Corrigendum.
AB  - [This corrects the article DOI: 10.1177/2333393616682549.].

PMID- 29662921
TI  - Progression of MDS-UPDRS Scores Over Five Years in De Novo Parkinson Disease from
      the Parkinson's Progression Markers Initiative Cohort.
AB  - Background: The Movement Disorder Society Unified Parkinson Disease Rating Scale
      (MDS-UDPRS) is a commonly used tool to measure Parkinson disease (PD)
      progression. Longitudinal changes in MDS-UPDRS scores in de novo PD have not been
      established. Objective: Determine progression rates of MDS-UPDRS scores in de
      novo PD. Methods: 362 participants from the Parkinson's Progression Markers
      Initiative, a multicenter longitudinal cohort study of de novo PD, were included.
      Longitudinal progression of MDS-UPDRS total and subscale scores were modeled
      using mixed model regression. Results: MDS-UPDRS scores increased in a linear
      fashion over five years in de novo PD. MDS-UPDRS total score increased an
      estimated 4.0 points/year, Part I 0.25 points/year, Part II 1.0 points/year, and
      Part III 2.4 points/year. Conclusions: The expected average progression of MDS
      UPDRS scores in de novo PD from this study can assist in clinical monitoring and
      provide comparative data for detection of disease modification in treatment
      trials.

PMID- 29662924
TI  - Corrigendum.
AB  - [This corrects the article DOI: 10.1177/2333721416644286.].

PMID- 29662923
TI  - Effects of Electrical Stimulation on Skeletal Muscle of Old Sedentary People.
AB  - Physical activity plays an important role in preventing muscle atrophy and
      chronic diseases in adults and in the elderly. Calcium (Ca2+) cycling and
      activation of specific molecular pathways are essential in contraction-induced
      muscle adaptation. This study attains human muscle sections and total homogenates
      prepared from biopsies obtained before (control) and after 9 weeks of training by
      electrical stimulation (ES) on a group of volunteers. The aim of the study was to
      investigate about the molecular mechanisms that support functional muscle
      improvement by ES. Evidences of kinase/phosphatase pathways activation after ES
      were obtained. Moreover, expression of Sarcalumenin, Calsequestrin and
      sarco/endoplasmic reticulum Ca2+-ATPase (Serca) isoforms was regulated by
      training. In conclusion, this work shows that neuromuscular ES applied to vastus
      lateralis muscle of sedentary seniors combines fiber remodeling with activation
      of Ca2+-Calmodulin molecular pathways and modulation of key Ca2+-handling
      proteins.

PMID- 29662925
TI  - Factors Associated With Improvements in Mortality and Morbidity Rates of Very-Low
      Birth-Weight Infants: A Cohort Study.
AB  - Objective. The objective of this study was to determine factors contributing to
      improvements in infant mortality rates (IMR) and composite morbidity-mortality in
      very-low-birth-weight (VLBW) infants after initiating a new perinatal program in
      2009 at Regional One Health (ROH). VLBW infants account for 67% of infant deaths.
      Design. This is a pre-/postintervention cohort study of prospectively gathered
      data. Population. VLBW infants delivered at ROH during the 2004 to 2015 study
      period. Setting. ROH is a Regional Perinatal Center affiliated with the
      University of Tennessee Health Science Center. Methods. We studied 2364
      consecutive VLBW infants. Multivariate models were applied to determine factors
      contributing significantly to the reduction in the outcome measures as well as
      trends over time. Main Outcome Measures. Primary outcomes were IMR and composite
      morbidity-mortality rates. Standardized, risk-adjusted mortality and composite
      morbidity ratios were also reported as defined by the Vermont Oxford Network.
      Results. Mortality declined from 15.5% in Pre-Implementation to 13.1% in Post
      Implementation (P = .093), corresponding to an 18% reduction in odds. The
      combined factors of composite morbidity-mortality rate decreased from 55.7% in
      Pre-Implementation to 43.9% in Post-Implementation (P < .0001), representing a
      38% reduction in odds. Standardized, risk-adjusted mortality and composite
      morbidity ratios improved during the study period from 20% above to 20% below the
      expected rate. Increases in the administration of antenatal steroids, surfactant
      administration, cesarean delivery, and perhaps other programmatic changes that
      were observational and unaccounted in the model were associated with improvements
      in outcome measures. Conclusions. Decreased mortality and composite morbidity
      mortality in VLBW infants delivered at ROH were found following the initiation of
      a new perinatal program.

PMID- 29662926
TI  - Colorectal Cancer Awareness: The Gastroenterology Resolution for the Future.

PMID- 29662927
TI  - Biliary Atresia - Too Few, Too Many Centers.

PMID- 29662928
TI  - A Step Forward in the Understanding of Structural and Functional Bowel Damage in
      Patients with Ulcerative Colitis.

PMID- 29662929
TI  - Colorectal Cancer Screening: What Is the Population's Opinion.
AB  - Background: Colorectal cancer (CRC) is the first cause of death by cancer in
      Portugal and mortality has been increasing in the last 30 years. Materials and
      Methods: During a raising awareness campaign performed by our Gastroenterology
      Department, in Setubal, Portugal, an anonymous written questionnaire was
      developed and presented in order to evaluate the population's knowledge and
      attitude regarding CRC screening. Results: The following results were reported:
      140 persons; mean age 54.6 years; 61.4% women; 22.1% had a family history of
      colorectal cancer. The main risk factors mentioned by the respondents were family
      history of CRC, previous history of intestinal polyps, and intestinal infection.
      Screening was considered useful by all respondents. About 60% of the respondents
      had been counselled, at least, on one screening technique, mainly by their
      general practitioner: colonoscopy in 31, fecal occult blood test in 44, and
      flexible sigmoidoscopy in 9. Most of the respondents had had the appropriate
      screening test, according to their age and family history. Fourteen of the
      respondents had not undergone the recommended screening. Their answers showed
      that this was due to fear of pain/discovering a disease as well as embarrassment.
      Conclusion: Although the majority of the respondents were aware of the importance
      of CRC screening, results show that there are still several misconceptions about
      risk factors, fear, and reluctance concerning the screening techniques. Awareness
      actions are useful to clarify possible questions and inform the population in
      order to increase compliance with screening.

PMID- 29662930
TI  - Biliary Atresia - Clinical Series.
AB  - Introduction: Biliary atresia is the main cause of death by hepatic failure and
      the main indication for liver transplant in children. This study aims to analyze
      the population with this diagnosis, treated between 2000 and 2015 at Hospital de
      Sao Joao. Material and Methods: Descriptive, observational, and retrospective
      study, including the patients with biliary atresia, diagnosed and treated between
      January 1, 2000 and December 31, 2015. We analyzed epidemiologic, clinical,
      biochemical, and image data, as well as registered complications and present
      status. Results: Eighteen patients were evaluated. The median age at time of
      Kasai portoenterostomy was 63 days of life, with better prognosis for those
      patients who had surgery before 72 days. The procedure was successful in 2/3 of
      cases. There was a significant association between recurrent cholangitis and
      survival. Five cases of transplant and 2 deaths, one of them after transplant,
      were registered. Survival with native liver was 77.8%, 72.2%, and 64.2% at 1, 5,
      and 10 years of follow-up, respectively. Discussion: The presentation and
      evolution of patients was similar to other studies. However, there was a higher
      surgical success and survival rates at 5 and 10 years of follow-up than most
      series. Age at surgery and recurrence of cholangitis were the only factors
      significantly related to prognosis. Conclusion: In spite of the low number of
      patients (1,125/year), our results were similar to those of other reference
      centers.

PMID- 29662931
TI  - Ulcerative Colitis: Are We Neglecting Its Progressive Character.
AB  - Introduction: Ulcerative colitis (UC) is a chronic disease but its progressive
      character, with structural damage, is insufficiently studied. Objectives: To
      analyze a group of patients without referral bias, regarding its clinical course,
      the morphological damage, and functional status. Methods: We evaluated UC
      patients diagnosed between January 1, 2000 and December 31, 2004, living in the
      direct referral area of the hospital and determined the medication use, colectomy
      rate, structural damage ("lead pipe," stenosis, pseudopolyps, fibrous bridges),
      and anorectal function (prospective evaluation with the Cleveland Clinic
      Incontinence Score [CCIS] and the Fecal Incontinence Quality of Life Scale).
      Results: We identified 104 patients, 47% female, with a mean age at diagnosis of
      38 +/- 17 years, 24% with proctitis, 57% with left colitis, and 19% with
      pancolitis. In 3 patients, it was not possible to obtain follow-up data. Of the
      studied patients, 56% needed corticosteroid therapy, 38% immunosuppressants, and
      16% anti-tumor necrosis factors (anti-TNFs). After a mean follow-up of 13 +/- 2
      years, we found structural damage in 25 patients (24%): 5% with proctocolectomy,
      15% with "lead pipe," 16% with pseudopolyps, and 3% with stenosis and fibrous
      bridges. Reference to functional anorectal disorders was identified in 49%,
      mostly previous and self-limited episodes of incontinence, but including
      persistent incontinence in 10% (CCIS 8 +/- 4.8). There was an increased incidence
      of structural damage and anorectal dysfunction in patients who needed
      corticosteroid therapy (p = 0.001), immunosuppressants (p < 0.001), and anti-TNFs
      (p = 0.002) and an association of structural damage with anorectal dysfunction (p
      < 0.001). There was no association between age and anorectal dysfunction,
      including incontinence episodes. Conclusions: UC is a disease with structural and
      functional consequences in a significant subset of patients. This should be
      incorporated when defining the therapeutic strategy.

PMID- 29662932
TI  - Combined Extensive Esophageal Squamous Papillomas and Florid Cardiac Gland
      Hyperplasia in a Patient with Adenocarcinoma.
AB  - We report a rare case of extensive esophageal squamous papillomas (ESPs)
      involving the entire esophagus and florid cardiac gland hyperplasia involving
      only the lower esophagus in a 39-year-old woman with heartburn and epigastric
      distress for the past 2 years. Previous esophagogastroduodenoscopy showed
      multiple ESPs involving the entire esophagus extending 38 cm from the esophageal
      orifice to the esophagogastric junction (EGJ). Additionally, prominent cardiac
      gland hyperplasia over the esophageal posterior wall was exhibited extending 12
      cm from the mid-esophagus to the EGJ. A biopsy obtained from the ESP area showed
      typical squamous papillomas and cardiac gland hyperplasia with no evidence of
      koilocytosis or malignancy. Polymerase chain reaction was negative for a variety
      of human papilloma virus DNAs. Subsequently, Siewert type II gastric cancer with
      submucosal elevation of the stomach was detected at the EGJ. Endoscopy showed a
      20-mm-thick lesion appearing to extend to the muscularis propria; subsequent
      biopsy showed invasive adenocarcinoma. Total gastrectomy with D2 lymph node
      dissection, splenectomy, and Roux-en-Y reconstruction were performed for the EGJ
      cancer. The patient died from widespread multiorgan metastasis within 2 years
      following surgery.

PMID- 29662933
TI  - Endometriosis: A Rare Cause of Large Bowel Obstruction.
AB  - Large bowel obstruction can result in significant morbidity and mortality,
      especially in cases of acute complete obstruction. There are many possible
      causes, the most common in adults being colorectal cancer. Endometriosis is a
      benign disease, and the most affected extragenital location is the bowel,
      especially the rectosigmoid junction. However, transmural involvement and acute
      occlusion are very rare events. We report an exceptional case of acute large
      bowel obstruction as the initial presentation of endometriosis. The differential
      diagnosis of colorectal carcinoma may be challenging, and this case emphasizes
      the need to consider intestinal endometriosis in females at a fertile age
      presenting with gastrointestinal symptoms and an intestinal mass causing complete
      large bowel obstruction.

PMID- 29662934
TI  - Bevacizumab for Refractory Gastrointestinal Bleeding in Rendu-Osler-Weber
      Disease.
AB  - Rendu-Osler-Weber disease, also known as hereditary hemorrhagic telangiectasia,
      is a rare autosomal dominant disorder which is often characterized by recurrent
      epistaxis, mucocutaneous and gastrointestinal telangiectasias, and visceral
      arteriovenous malformations. Patients with gastrointestinal involvement can
      present with a wide spectrum of severity, which may vary from uncomplicated iron
      deficiency anemia to continuous and refractory bleeding. We present the case of a
      62-year-old female, who was admitted with anemia following several episodes of
      melena, and whose endoscopic examination revealed multiple angiodysplasias in the
      stomach and small bowel. Despite endoscopic and medical treatment attempts with
      hormonal agents and octreotide, she developed persistent hemorrhage and severe
      anemia, requiring frequent red blood cell transfusions. Immediately after
      initiating bevacizumab (7.5 mg/kg, every 3 weeks), complete cessation of bleeding
      episodes was observed. Currently, after 1 year of follow-up, she maintained
      sustained remission without the occurrence of adverse events.

PMID- 29662935
TI  - Ligate-and-Resect Technique for Resection of a Large Pseudo-Pedunculated
      Subepithelial Lesion in the Ascending Colon.

PMID- 29662936
TI  - Gastric Metastasis of Breast Cancer after 20 Years.

PMID- 29662937
TI  - A Rare Cause of Multisegmental Gastrointestinal Ulceration.

PMID- 29662938
TI  - Portal Vein Aneurysm Mimicking a Liver Nodule.

PMID- 29662939
TI  - LTP or LTD? Modeling the Influence of Stress on Synaptic Plasticity.
AB  - In cognitive memory, long-term potentiation (LTP) has been shown to occur when
      presynaptic and postsynaptic activities are highly correlated and glucocorticoid
      concentrations are in an optimal (i.e., low normal) range. In all other
      conditions, LTP is attenuated or even long-term depression (LTD) occurs. In this
      paper, we focus on NMDA receptor (NMDA-R)-dependent LTP and LTD, two processes
      involving various molecular mechanisms. To understand which of these mechanisms
      are indispensable for explaining the experimental evidence reported in the
      literature, we here propose a parsimonious model of NMDA-R-dependent synaptic
      plasticity. Central to this model are two processes. First, AMPA receptor-subunit
      trafficking; and second, glucocorticoid-dependent modifications of the brain
      derived neurotrophic factor (BDNF)-receptor system. In 2008, we have published a
      core model, which contained the first process, while in the current paper we
      present an extended model, which also includes the second process. Using the
      extended model, we could show that stress attenuates LTP, while it enhances LTD.
      These simulation results are in agreement with experimental findings from other
      labs. In 2013, surprising experimental evidence showed that the GluA1 C-tail is
      unnecessary for LTP. When using our core model in its original form, our
      simulations already predicted that there would be no requirement for the GluA1 C
      tail for LTP, allowing to eliminate a redundant mechanism from our model. In
      summary, we present a mathematical model that displays reduced complexity and is
      useful for explaining when and how LTP or LTD occurs at synapses during cognitive
      memory formation.

PMID- 29662940
TI  - Large Scale In Vivo Recording of Sensory Neuron Activity with GCaMP6.
AB  - Greater emphasis on the study of intact cellular networks in their physiological
      environment has led to rapid advances in intravital imaging of the central
      nervous system (CNS), while the peripheral system remains largely unexplored. To
      assess large networks of sensory neurons, we selectively label primary afferents
      with GCaMP6s in male and female C57bl/6 mice and visualize their functional
      responses to peripheral stimulation in vivo. We show that we are able to monitor
      the activity of hundreds of sensory neurons simultaneously, with sufficient
      sensitivity to detect, in most cases, single action potentials with a typical
      rise time of around 200 ms, and an exponential decay with a time constant of
      approximately 700 ms. With this technique we are able to characterize the
      responses of large populations of sensory neurons to innocuous and noxious
      mechanical and thermal stimuli under normal and inflammatory conditions. We
      demonstrate that the majority of primary afferents are polymodal with between 50
      80% of thermally sensitive DRG neurons responding also to noxious mechanical
      stimulation. We also specifically assess the small population of peripheral cold
      neurons and demonstrate significant sensitization to cooling after a model of
      sterile and persistent inflammation, with significantly increased sensitivity
      already at decreases of 5 degrees C when compared to uninflamed responses. This
      not only reveals interesting new insights into the (patho)physiology of the
      peripheral nervous system but also demonstrates the sensitivity of this imaging
      technique to physiological changes in primary afferents.

PMID- 29662941
TI  - The Extracellular Matrix and Remyelination Strategies in Multiple Sclerosis.

PMID- 29662942
TI  - Measuring and Validating the Levels of Brain-Derived Neurotrophic Factor in Human
      Serum.
AB  - Brain-derived neurotrophic factor (BDNF) secreted by neurons is a significant
      component of synaptic plasticity. In humans, it is also present in blood
      platelets where it accumulates following its biosynthesis in megakaryocytes. BDNF
      levels are thus readily detectable in human serum and it has been abundantly
      speculated that they may somehow serve as an indicator of brain function.
      However, there is a great deal of uncertainty with regard to the range of BDNF
      levels that can be considered normal, how stable these values are over time and
      even whether BDNF levels can be reliably measured in serum. Using monoclonal
      antibodies and a sandwich ELISA, this study reports on BDNF levels in the serum
      of 259 volunteers with a mean value of 32.69 +/- 8.33 ng/ml (SD). The mean value
      for the same cohort after 12 months was not significantly different (N = 226,
      32.97 +/- 8.36 ng/ml SD, p = 0.19). Power analysis of these values indicates that
      relatively large cohorts are necessary to identify significant differences,
      requiring a group size of 60 to detect a 20% change. The levels determined by
      ELISA could be validated by Western blot analyses using a BDNF monoclonal
      antibody. While no association was observed with gender, a weak, positive
      correlation was found with age. The overall conclusions are that BDNF levels can
      be reliably measured in human serum, that these levels are quite stable over one
      year, and that comparisons between two populations may only be meaningful if
      cohorts of sufficient sizes are assembled.

PMID- 29662943
TI  - Evidence Integration in Natural Acoustic Textures during Active and Passive
      Listening.
AB  - Many natural sounds can be well described on a statistical level, for example,
      wind, rain, or applause. Even though the spectro-temporal profile of these
      acoustic textures is highly dynamic, changes in their statistics are indicative
      of relevant changes in the environment. Here, we investigated the neural
      representation of change detection in natural textures in humans, and
      specifically addressed whether active task engagement is required for the neural
      representation of this change in statistics. Subjects listened to natural
      textures whose spectro-temporal statistics were modified at variable times by a
      variable amount. Subjects were instructed to either report the detection of
      changes (active) or to passively listen to the stimuli. A subset of passive
      subjects had performed the active task before (passive-aware vs passive-naive).
      Psychophysically, longer exposure to pre-change statistics was correlated with
      faster reaction times and better discrimination performance. EEG recordings
      revealed that the build-up rate and size of parieto-occipital (PO) potentials
      reflected change size and change time. Reduced effects were observed in the
      passive conditions. While P2 responses were comparable across conditions, slope
      and height of PO potentials scaled with task involvement. Neural source
      localization identified a parietal source as the main contributor of change
      specific potentials, in addition to more limited contributions from auditory and
      frontal sources. In summary, the detection of statistical changes in natural
      acoustic textures is predominantly reflected in parietal locations both on the
      skull and source level. The scaling in magnitude across different levels of task
      involvement suggests a context-dependent degree of evidence integration.

PMID- 29662944
TI  - Combined Blockade of Interleukin-1alpha and -1beta Signaling Protects Mice from
      Cognitive Dysfunction after Traumatic Brain Injury.
AB  - Diffuse activation of interleukin-1 inflammatory cytokine signaling after
      traumatic brain injury (TBI) elicits progressive neurodegeneration and
      neuropsychiatric dysfunction, and thus represents a potential opportunity for
      therapeutic intervention. Although interleukin (IL)-1alpha and IL-1beta both
      activate the common type 1 IL-1 receptor (IL-1RI), they manifest distinct injury
      specific roles in some models of neurodegeneration. Despite its potential
      relevance to treating patients with TBI, however, the individual contributions of
      IL-1alpha and IL-1beta to TBI-pathology have not been previously investigated. To
      address this need, we applied genetic and pharmacologic approaches in mice to
      dissect the individual contributions of IL-1alpha, IL-beta, and IL-1RI signaling
      to the pathophysiology of fluid percussion-mediated TBI, a model of mixed focal
      and diffuse TBI. IL-1RI ablation conferred a greater protective effect on brain
      cytokine expression and cognitive function after TBI than did individual IL
      1alpha or IL-1beta ablation. This protective effect was recapitulated by
      treatment with the drug anakinra, a recombinant naturally occurring IL-1RI
      antagonist. Our data thus suggest that broad targeting of IL-1RI signaling is
      more likely to reduce neuroinflammation and preserve cognitive function after TBI
      than are approaches that individually target IL-1alpha or IL-1beta signaling.

PMID- 29662945
TI  - Metabotropic Glutamate Receptor 2/3 (mGluR2/3) Activation Suppresses TRPV1
      Sensitization in Mouse, But Not Human, Sensory Neurons.
AB  - The use of human tissue to validate putative analgesic targets identified in
      rodents is a promising strategy for improving the historically poor translational
      record of preclinical pain research. We recently demonstrated that in mouse and
      human sensory neurons, agonists for metabotropic glutamate receptors 2 and 3
      (mGluR2/3) reduce membrane hyperexcitability produced by the inflammatory
      mediator prostaglandin E2 (PGE2). Previous rodent studies indicate that mGluR2/3
      can also reduce peripheral sensitization by suppressing inflammation-induced
      sensitization of TRPV1. Whether this observation similarly translates to human
      sensory neurons has not yet been tested. We found that activation of mGluR2/3
      with the agonist APDC suppressed PGE2-induced sensitization of TRPV1 in mouse,
      but not human, sensory neurons. We also evaluated sensory neuron expression of
      the gene transcripts for mGluR2 (Grm2), mGluR3 (Grm3), and TRPV1 (Trpv1). The
      majority of Trpv1+ mouse and human sensory neurons expressed Grm2 and/or Grm3,
      and in both mice and humans, Grm2 was expressed in a greater percentage of
      sensory neurons than Grm3. Although we demonstrated a functional difference in
      the modulation of TRPV1 sensitization by mGluR2/3 activation between mouse and
      human, there were no species differences in the gene transcript colocalization of
      mGluR2 or mGluR3 with TRPV1 that might explain this functional difference. Taken
      together with our previous work, these results suggest that mGluR2/3 activation
      suppresses only some aspects of human sensory neuron sensitization caused by
      PGE2. These differences have implications for potential healthy human voluntary
      studies or clinical trials evaluating the analgesic efficacy of mGluR2/3 agonists
      or positive allosteric modulators.

PMID- 29662946
TI  - Differences in the Electrophysiological Properties of Mouse Somatosensory Layer
      2/3 Neurons In Vivo and Slice Stem from Intrinsic Sources Rather than a Network
      Generated High Conductance State.
AB  - Synaptic activity in vivo can potentially alter the integration properties of
      neurons. Using recordings in awake mice, we targeted somatosensory layer 2/3
      pyramidal neurons and compared neuronal properties with those from slices.
      Pyramidal cells in vivo had lower resistance and gain values, as well as broader
      spikes and increased spike frequency adaptation compared to the same cells in
      slices. Increasing conductance in neurons using dynamic clamp to levels observed
      in vivo, however, did not lessen the differences between in vivo and slice
      conditions. Further, local application of tetrodotoxin (TTX) in vivo blocked
      synaptic-mediated membrane voltage fluctuations but had little impact on
      pyramidal cell membrane input resistance and time constant values. Differences in
      electrophysiological properties of layer 2/3 neurons in mouse somatosensory
      cortex, therefore, stem from intrinsic sources separate from synaptic-mediated
      membrane voltage fluctuations.

PMID- 29662947
TI  - Cortical Measures of Phoneme-Level Speech Encoding Correlate with the Perceived
      Clarity of Natural Speech.
AB  - In real-world environments, humans comprehend speech by actively integrating
      prior knowledge (P) and expectations with sensory input. Recent studies have
      revealed effects of prior information in temporal and frontal cortical areas and
      have suggested that these effects are underpinned by enhanced encoding of speech
      specific features, rather than a broad enhancement or suppression of cortical
      activity. However, in terms of the specific hierarchical stages of processing
      involved in speech comprehension, the effects of integrating bottom-up sensory
      responses and top-down predictions are still unclear. In addition, it is unclear
      whether the predictability that comes with prior information may differentially
      affect speech encoding relative to the perceptual enhancement that comes with
      that prediction. One way to investigate these issues is through examining the
      impact of P on indices of cortical tracking of continuous speech features. Here,
      we did this by presenting participants with degraded speech sentences that either
      were or were not preceded by a clear recording of the same sentences while
      recording non-invasive electroencephalography (EEG). We assessed the impact of
      prior information on an isolated index of cortical tracking that reflected
      phoneme-level processing. Our findings suggest the possibility that prior
      information affects the early encoding of natural speech in a dual manner.
      Firstly, the availability of prior information, as hypothesized, enhanced the
      perceived clarity of degraded speech, which was positively correlated with
      changes in phoneme-level encoding across subjects. In addition, P induced an
      overall reduction of this cortical measure, which we interpret as resulting from
      the increase in predictability.

PMID- 29662949
TI  - Dealing With Deans and Academic Medical Center Leadership: Advice From Leaders.
AB  - The 2017 Association of Pathology Chairs Annual Meeting included a session for
      department chairs and other department leaders on "how to deal with deans and
      academic medical center leadership." The session was focused on discussing ways
      to foster positive relationships with university, medical school, and health
      system leaders, and productively address issues and opportunities with them.
      Presentations and a panel discussion were provided by 4 former pathology chairs
      who subsequently have served as medical deans and in other leadership positions
      including university provost, medical center CEO, and health system board chair.
      There was a strong consensus among the participants on how best to deal with
      superiors about problems, conflicts, and requests for additional resources and
      authority. The importance of teamwork and accountability in developing a
      constructive and collaborative relationship with leaders and peers was discussed
      in detail. Effectiveness in communication, negotiation, and departmental advocacy
      were highlighted as important skills. As limited resources and increased
      regulations have become growing problems for universities and health systems,
      internal stress and competition have increased. In this rapidly changing
      environment, advice on how chairs can interact most productively with
      institutional leaders is becoming increasingly important.

PMID- 29662948
TI  - Reduced Orexin System Function Contributes to Resilience to Repeated Social
      Stress.
AB  - Exposure to stress increases the risk of developing affective disorders such as
      depression and post-traumatic stress disorder (PTSD). However, these disorders
      occur in only a subset of individuals, those that are more vulnerable to the
      effects of stress, whereas others remain resilient. The coping style adopted to
      deal with the stressor, either passive or active coping, is related to
      vulnerability or resilience, respectively. Important neural substrates that
      mediate responses to a stressor are the orexins. These neuropeptides are altered
      in the cerebrospinal fluid of patients with stress-related illnesses such as
      depression and PTSD. The present experiments used a rodent social defeat model
      that generates actively coping rats and passively coping rats, which we have
      previously shown exhibit resilient and vulnerable profiles, respectively, to
      examine if orexins play a role in these stress-induced phenotypes. In situ
      radiolabeling and qPCR revealed that actively coping rats expressed significantly
      lower prepro-orexin mRNA compared with passively coping rats. This led to the
      hypothesis that lower levels of orexins contribute to resilience to repeated
      social stress. To test this hypothesis, rats first underwent 5 d of social defeat
      to establish active and passive coping phenotypes. Then, orexin neurons were
      inhibited before each social defeat for three additional days using designer
      receptors exclusively activated by designer drugs (DREADDs). Inhibition of
      orexins increased social interaction behavior and decreased depressive-like
      behavior in the vulnerable population of rats. Indeed, these data suggest that
      lowering orexins promoted resilience to social defeat and may be an important
      target for treatment of stress-related disorders.

PMID- 29662950
TI  - Strong coupling superconductivity in a quasiperiodic host-guest structure.
AB  - We examine the low-temperature states supported by the quasiperiodic host-guest
      structure of elemental bismuth at high pressure, Bi-III. Our electronic transport
      and magnetization experiments establish Bi-III as a rare example of type II
      superconductivity in an element, with a record upper critical field of ~ 2.5 T,
      unusually strong electron-phonon coupling, and an anomalously large, linear
      temperature dependence of the electrical resistivity in the normal state. These
      properties may be attributed to the peculiar phonon spectrum of incommensurate
      host-guest structures, which exhibit additional quasi-acoustic sliding modes,
      suggesting a pathway toward strong coupling superconductivity with the potential
      for enhanced transition temperatures and high critical fields.

PMID- 29662951
TI  - High-performance and scalable metal-chalcogenide semiconductors and devices via
      chalco-gel routes.
AB  - We report a general strategy for obtaining high-quality, large-area metal
      chalcogenide semiconductor films from precursors combining chelated metal salts
      with chalcoureas or chalcoamides. Using conventional organic solvents, such
      precursors enable the expeditious formation of chalco-gels, which are easily
      transformed into the corresponding high-performance metal-chalcogenide thin films
      with large, uniform areas. Diverse metal chalcogenides and their alloys (MQ x : M
      = Zn, Cd, In, Sb, Pb; Q = S, Se, Te) are successfully synthesized at relatively
      low processing temperatures (<400 degrees C). The versatility of this scalable
      route is demonstrated by the fabrication of large-area thin-film transistors
      (TFTs), optoelectronic devices, and integrated circuits on a 4-inch Si wafer and
      2.5-inch borosilicate glass substrates in ambient air using CdS, CdSe, and In2Se3
      active layers. The CdSe TFTs exhibit a maximum field-effect mobility greater than
      300 cm2 V-1 s-1 with an on/off current ratio of >107 and good operational
      stability (threshold voltage shift < 0.5 V at a positive gate bias stress of 10
      ks). In addition, metal chalcogenide-based phototransistors with a
      photodetectivity of >1013 Jones and seven-stage ring oscillators operating at a
      speed of ~2.6 MHz (propagation delay of < 27 ns per stage) are demonstrated.

PMID- 29662952
TI  - Bursting at the seams: Rippled monolayer bismuth on NbSe2.
AB  - Bismuth, one of the heaviest semimetals in nature, ignited the interest of the
      materials physics community for its potential impact on topological quantum
      material systems that use its strong spin-orbit coupling and unique orbital
      hybridization. In particular, recent theoretical predictions of unique
      topological and superconducting properties of thin bismuth films and interfaces
      prompted intense research on the growth of submonolayers to a few monolayers of
      bismuth on different substrates. Similar to bulk rhombohedral bismuth, the
      initial growth of bismuth films on most substrates results in buckled bilayers
      that grow in either the (111) or (110) directions, with a lattice constant close
      to that of bulk Bi. By contrast, we show a new growth pattern for bismuth
      monolayers on NbSe2. We find that the initial growth of Bi can form a strongly
      bonded commensurate layer, resulting in a compressively strained two-dimensional
      (2D) triangular lattice. We also observed unique pattern of 1D ripples and domain
      walls is observed. The single layer of bismuth also introduces strong marks on
      the electronic properties at the surface.

PMID- 29662953
TI  - Accelerated discovery of metallic glasses through iteration of machine learning
      and high-throughput experiments.
AB  - With more than a hundred elements in the periodic table, a large number of
      potential new materials exist to address the technological and societal
      challenges we face today; however, without some guidance, searching through this
      vast combinatorial space is frustratingly slow and expensive, especially for
      materials strongly influenced by processing. We train a machine learning (ML)
      model on previously reported observations, parameters from physiochemical
      theories, and make it synthesis method-dependent to guide high-throughput (HiTp)
      experiments to find a new system of metallic glasses in the Co-V-Zr ternary.
      Experimental observations are in good agreement with the predictions of the
      model, but there are quantitative discrepancies in the precise compositions
      predicted. We use these discrepancies to retrain the ML model. The refined model
      has significantly improved accuracy not only for the Co-V-Zr system but also
      across all other available validation data. We then use the refined model to
      guide the discovery of metallic glasses in two additional previously unreported
      ternaries. Although our approach of iterative use of ML and HiTp experiments has
      guided us to rapid discovery of three new glass-forming systems, it has also
      provided us with a quantitatively accurate, synthesis method-sensitive predictor
      for metallic glasses that improves performance with use and thus promises to
      greatly accelerate discovery of many new metallic glasses. We believe that this
      discovery paradigm is applicable to a wider range of materials and should prove
      equally powerful for other materials and properties that are synthesis path
      dependent and that current physiochemical theories find challenging to predict.

PMID- 29662954
TI  - Crystal nucleation in metallic alloys using x-ray radiography and machine
      learning.
AB  - The crystallization of solidifying Al-Cu alloys over a wide range of conditions
      was studied in situ by synchrotron x-ray radiography, and the data were analyzed
      using a computer vision algorithm trained using machine learning. The effect of
      cooling rate and solute concentration on nucleation undercooling, crystal
      formation rate, and crystal growth rate was measured automatically for thousands
      of separate crystals, which was impossible to achieve manually. Nucleation
      undercooling distributions confirmed the efficiency of extrinsic grain refiners
      and gave support to the widely assumed free growth model of heterogeneous
      nucleation. We show that crystallization occurred in temporal and spatial bursts
      associated with a solute-suppressed nucleation zone.

PMID- 29662955
TI  - Multiple heteroatom substitution to graphene nanoribbon.
AB  - Substituting heteroatoms into nanostructured graphene elements, such as graphene
      nanoribbons, offers the possibility for atomic engineering of electronic
      properties. To characterize these substitutions, functionalized atomic force
      microscopy (AFM)-a tool to directly resolve chemical structures-is one of the
      most promising tools, yet the chemical analysis of heteroatoms has been rarely
      performed. We synthesized multiple heteroatom-substituted graphene nanoribbons
      and showed that AFM can directly resolve elemental differences and can be
      correlated to the van der Waals radii, as well as the modulated local electron
      density caused by the substitution. This elemental-sensitive measurement takes an
      important step in the analysis of functionalized two-dimensional carbon
      materials.

PMID- 29662956
TI  - Experimental signatures of spin superfluid ground state in canted antiferromagnet
      Cr2O3 via nonlocal spin transport.
AB  - Spin superfluid is a novel emerging quantum matter arising from the Bose-Einstein
      condensate (BEC) of spin-1 bosons. We demonstrate the spin superfluid ground
      state in canted antiferromagnetic Cr2O3 thin film at low temperatures via
      nonlocal spin transport. A large enhancement of the nonlocal spin signal is
      observed below ~20 K, and it saturates from ~5 down to 2 K. We show that the
      spins can propagate over very long distances (~20 MUm) in such spin superfluid
      ground state and that the nonlocal spin signal decreases very slowly as the
      spacing increases with an inverse relationship, which is consistent with
      theoretical prediction. Furthermore, spin superfluidity has been investigated in
      the canted antiferromagnetic phase of the (11[Formula: see text]0)-oriented Cr2O3
      film, where the magnetic field dependence of the associated critical temperature
      follows a 2/3 power law near the critical point. The experimental demonstration
      of the spin superfluid ground state in canted antiferromagnet will be extremely
      important for the fundamental physics on the BEC of spin-1 bosons and paves the
      way for future spin supercurrent devices, such as spin-Josephson junctions.

PMID- 29662958
TI  - Laparoscopic Heminephrectomy of Chronically Obstructed Horseshoe Kidney Moiety
      with Staghorn Calculus, Massive Pyonephrosis, and Xanthogranulomatous
      Pyelonephritis.
AB  - Laparoscopic heminephrectomy was performed in a 64-year-old woman with a
      chronically obstructed horseshoe kidney moiety. More than 3000 cc of pyonephrosis
      was drained through two percutaneous nephrostomy tubes for infection control
      before left moiety laparoscopic resection. This case report attests to the
      feasibility of laparoscopic resection of a massively obstructed horseshoe kidney
      when performed in a staged manner after prolonged drainage. Since an incision was
      required for removal of the large specimen, ligation of the horseshoe isthmus was
      completed through the same incision after hilar control and laparoscopic
      mobilization of the moiety were completed.

PMID- 29662959
TI  - Quarter Century Management of Chronic Ureteropelvic Junction Obstruction in a
      Solitary Kidney with a Ureteral Stent.
AB  - Background: The ureteral stent provides a conduit for urinary drainage from the
      kidney to the bladder and is integral to contemporary urologic practice. A
      ureteral stent is often utilized in acute conditions to prevent or overcome
      obstruction; however, in nonsurgical patients, because of disease or preference,
      a ureteral stent may be used as a last resort for long-term management of a
      stricture in lieu of a nephrostomy tube. This case highlights a patient whose
      chronic ureteral obstruction has been managed with an indwelling ureteral stent
      for 25 years; remarkably, stent exchanges are currently required only every 2
      years. Case Presentation: A 33-year-old man initially presented with a solitary
      left kidney and a ureteropelvic junction obstruction. The patient's right kidney
      was nonfunctioning since childhood because of a presumed ureteropelvic junction
      obstruction with grade IV hydronephrosis. The patient underwent two failed open
      repairs of the left kidney in the 1980s, resulting in a totally intrarenal,
      constricted renal pelvis; an endopyelotomy in 1992 also failed and required
      angioembolizaton of a segmental renal vessel. The patient refused any further
      surgical procedures and thus has been managed exclusively with a 7/14F * 28 cm
      endopyelotomy stent (Boston Scientific(r)) for 25 years; the interval between
      stent changes was slowly expanded until they are now being done at 2-year
      intervals. The patient has not developed recurrent urinary tract infections,
      stent colic, or stent encrustation. Conclusion: Patients who require chronic
      indwelling ureteral stents are rare. In this situation, with careful monitoring,
      the interval between stent exchanges was extended to 2 years, thereby precluding
      a chronic nephrostomy tube.

PMID- 29662957
TI  - New York Physicians' Perspectives and Knowledge of the State Medical Marijuana
      Program.
AB  - Introduction: In 2014, New York (NY) became the 23rd state to legalize medical
      marijuana (MMJ). The purpose of this survey was to collect data about practicing
      NY physicians' comfort level, opinions, and experience in recommending or
      supporting patient use of MMJ. Materials and Methods: An anonymous web-based
      survey was distributed to medical societies and to academic departments in
      medical schools within NY. Results: A total of 164 responses were analyzed.
      Physician participants were primarily located in New York City and surrounding
      areas. The majority (71%) agreed that MMJ should be an option available to
      patients. Most respondents were not registered to certify MMJ in NY, but were
      willing to refer patients to registered physicians. Common reasons for not
      registering included specialty and federal status of cannabis. More than 75%
      reported having patients who used cannabis for symptom control, and 50% reported
      having patients who inquired about MMJ within the past year. Most respondents are
      willing to discuss MMJ with their patients, but had little familiarity with the
      state program and a modest knowledge of the endocannabinoid system. Pain was a
      common symptom for which cannabis was recommended by registered physicians (69%)
      and purportedly used by patients (83%). Most respondents would consider MMJ as an
      adjuvant to opioids, and 84% believed opioids have greater risks than MMJ.
      Conclusion: Given that the majority of surveyed physicians support MMJ as an
      option for patients, few are registered and have adequate knowledge of MMJ.
      Although our study sample is small and geographically limited, our survey results
      highlight key physician issues that are likely applicable to practitioners in
      other states. Concerted efforts are needed at the federal, state, and academic
      levels to provide practitioners with evidence-based guidelines for the safe use
      of MMJ.

PMID- 29662960
TI  - Impact of Oral Hygiene Discontinuation on Supragingival and Salivary Microbiomes.
AB  - The purpose of the present study was to characterize and compare supragingival
      and salivary microbiotas during a 10-d period of oral hygiene discontinuation. We
      tested the hypothesis that the composition of the salivary microbiota will
      reflect local microbial changes associated with accumulated biofilm formation and
      maturation. Pooled supragingival plaque (n = 145) and stimulated saliva (n = 145)
      samples were collected and plaque and gingival indices were recorded from 29
      orally healthy individuals at baseline, during oral hygiene discontinuation (days
      4, 7, and 10), and 14 d after resumption of oral hygiene. Supragingival and
      salivary microbiotas were processed by next-generation sequencing (Human Oral
      Microbe Identification using Next Generation Sequencing) and microbial community
      profiles were compared. Microbial composition of supragingival plaque samples
      collected after 4, 7, and 10 d of oral hygiene discontinuation, as well as 14 d
      after reuptake of oral hygiene, differed significantly from baseline samples, by
      a 3-fold increase in relative abundance Leptotrichia species and a 2-fold
      decrease in Streptococcus species (adjusted P < 0.01). In saliva samples, a
      significant increase in relative abundance of Leptotrichia species (adjusted P <
      0.01) was evident at day 7 but completely reversed 14 d after resumption of oral
      hygiene. While the salivary microbiota was resistant to accumulated local biofilm
      formation, data from this study showed that compositional changes of
      supragingival microbiotas were not reversed 14 d after resumption of oral
      hygiene, despite the restoration of plaque to baseline levels.
      (ClinicalTrials.gov UCPH_OI_002, NCT02913235). Knowledge Transfer Statement: Data
      from this study showed compositional changes of supragingival microbiotas as a
      consequence of a 10-d period of oral hygiene discontinuation, that was not
      reversed 14 d after resumption of oral hygiene. Notably, oral hygiene
      discontinuation was associated with a significant increase in relative abundance
      of potential cariogenic Leptotrichia species and a decrease in Streptococcus
      species. Thus, findings from this study highlight the necessity of regular oral
      hygiene in the maintenance of oral homeostasis.

PMID- 29662961
TI  - Biopsychosocial view to pseudocyesis: A narrative review.
AB  - Background: Pseudocyesis is a psychopathological clinical syndrome in which a non
      pregnant woman firmly believes herself to be pregnant and manifests many symptoms
      and signs of pregnancy. Although the exact etiology of pseudocyesis has not been
      determined. Objective: This study was conducted with the aim of assessing the
      biopsychosocial view to pseudocyesis. Materials and Methods: A comprehensive
      search in electronic databases such as Google Scholar, PubMed, ScienceDirect, Web
      of Science, and Scopus was conducted between 1943-2016 to retrieve pseudocyesis
      related articles. For this purpose, 1149 articles were collected and 66 items
      were used. Results: Findings were classified into 2 main categories: a)
      pseudocyesis etiology, which could include (biological psychological factors and
      psychiatric disorders, and social factors); and b) pseudocyesis management.
      Conclusion: Pseudocyesis results from a multidimensional group of factors, and a
      holistic and comprehensive approach should be taken to its treatment. Cooperation
      between gynecologists and psychiatrists would likely be useful in addressing the
      condition.

PMID- 29662963
TI  - Facilitating and inhibiting factors related to treatment adherence in women with
      polycystic ovary syndrome: A qualitative study.
AB  - Background: Adherence issues in polycystic ovary syndrome (PCOS) patients have
      not been examined thoroughly. Patients report prolonged periods of treatment and
      side effects of the drug as the most common reason for withdrawal from treatment.
      To improve the effective management of PCOS patients, it is fundamental to
      understand facilitating and inhibiting factors to treatment adherence. Objective:
      To explore facilitating/inhibiting factors related to treatment adherence among
      PCOS patients. Materials and Methods: This was a qualitative study with a
      purposive sample of women with confirmed diagnosis of PCOS. The data were
      collected via 20 in-depth semi-structured interviews with women aged between 21
      34 yr. A qualitative content analysis was used to analyze the data. Results: Five
      themes were identified which described different types of facilitating/
      inhibiting factors to treatment adherence. Inhibiting factors included financial
      issues, patient-related, disease-related, and health care provider-related
      factors; while social factors were found to be both facilitating and inhibiting.
      Conclusion: The findings suggest that successful adherence to PCOS treatment is
      highly dependent on patients recognizing and adapting to financial, social, and
      health care related inhibiting factors. It is also crucial for clinicians and
      policy makers to recognize these key inhibiting factors in order to improve
      treatment outcomes.

PMID- 29662962
TI  - The relation of maternal hypothyroidism and hypothyroxinemia during pregnancy on
      preterm birth: An updated systematic review and meta-analysis.
AB  - Background: The clinical consequences of hypothyroidism and hypothyroxinemia
      during pregnancy such as preterm birth are not still clear. Objective: The aim of
      this meta-analysis was to estimate the relation of clinical and subclinical
      hypothyroidism and hypothyroxinemia during pregnancy and preterm birth. Materials
      and Methods: In this meta-analysis, Preferred Reporting Items for Systematic
      review and Meta-Analysis were utilized. Searching the cohort studies were done by
      two researchers independently without any restrictions on Scopus, PubMed, Science
      Direct, Embase, Web of Science, CINAHL, Cochrane, EBSCO and Google Scholar
      databases up to 2017. The heterogeneity of the studies was checked by the
      Cochran's Q test and I2 index. Both random and fixed-effects models were used for
      combining the relative risk and 95% confidence intervals. Data were analyzed
      using Comprehensive Meta-Analysis software version 2. Results: Twenty-three
      studies were included in the meta-analysis. The relative risks of the clinical
      hypothyroidism, subclinical hypothyroidism and hypothyroxinemia during pregnancy
      on preterm birth was estimated 1.30 (95% CI: 1.05-1.61, p=0.013, involving 20079
      cases and 2452817 controls), 1.36 (95% CI: 1.09-1.68, p=0.005, involving 3580
      cases and 64885 controls) and 1.31 (95% CI: 1.04-1.66, p=0.020, involving 1078
      cases and 44377 controls), respectively. Conclusion: The incidence of preterm
      birth was higher among mothers with clinical and subclinical hypothyroidism or
      hypothyroxinemia during pregnancy compared to euthyroid mothers, and these
      relations were significant. Therefore, gynecologists and endocrinologists should
      manage these patients to control the incidence of adverse pregnancy outcomes such
      as preterm birth.

PMID- 29662964
TI  - Comparison of the effects of Ginger extract with clomiphene citrate on sex
      hormones in rats with polycystic ovarian syndrome.
AB  - Background: Polycystic ovarian syndrome (PCOS) is the most common endocrine
      disorder in women which affect fertility. Clomiphene citrate is used as first
      line treatment for this disorder, which is associated with some complications and
      therapeutic resistance. Objective: In this research, we compare the effectiveness
      of ginger with clomiphene on sexual hormones such as Luteinizing hormone (LH),
      Follicle-stimulating hormone (FSH), estrogen and progesterone in order to treat
      PCOS effectively with fewer side effects. Materials and Methods: In this
      experimental study, 63 adult female rats (170-200 gr) were studied and divided
      randomly into 9 groups as control (not received any interventional substance for
      60 and 89 days), sham (were given distilled water and ethyl alcohol
      intraperitoneally daily for 60 and 89 days), and 7 experimental groups receiving
      estradiol valerate (PCOS inducing agent, intramuscular) alone and with 100 mg/kg
      clomiphene or different doses of ginger extract (175 and 350 mg/kg) orally daily
      for 60 and 89 days. Sexual hormones were analyzed and compared in different
      groups. Results: Our results showed that in the PCOS-induced group, LH and
      estrogen concentration increased while progesterone and FSH concentration
      decreased remarkably (p<0.05) as compared to control group. Furthermore, in
      groups receiving clomiphene and ginger extract, we demonstrated significant
      (p<0.05) improvement in hormonal secretion as compared to the PCOS-induced group.
      Clomiphene, compared with the lower dose of ginger extract, had a better
      improving effect on balancing sexual hormones in PCOS. Moreover, ginger extract
      at higher doses has better effects in improving PCOS. Conclusion: As the long
      term administration of clomiphene citrate has some side effects, the use of
      ginger as a herbal medicine without any side effects at high doses can be an
      effective and good alternative in improving PCOS.

PMID- 29662965
TI  - Relationship between human leukocyte antigen (HLA)-DQA1*0102/HLA-DQB1*0602
      polymorphism and preeclampsia.
AB  - Background: Preeclampsia is a condition associated with systemic disorders in the
      mother and the fetus. However, the exact causes of preeclampsia are unknown, but
      several genetics and environmental factors play role in development of this
      disease. Major histocompatibility complex role is very important during pregnancy
      through which the fetus is not rejected by mother's immune system. Objective: In
      this study, we investigated the relationship of the human leukocyte antigen (HLA)
      DQA1*0102/HLA-DQB1*0602 polymorphism with preeclampsia. Materials and Methods:
      Genomic DNA of 181 pregnant women with a history of preeclampsia as the case
      group and 228 pregnant women with no history of preeclampsia as the controls were
      extracted. The HLA-DQA1*0102/HLA-DQB1*0602 polymorphisms of all DNA samples were
      identified by the SSP-PCR method. Frequencies difference of variables between
      case and control groups were calculated by Chi-square test. The ethnic origin of
      the participants in this study was extracted from their medical records. Results:
      There was a significant association between preeclampsia and Sistani ethnic group
      (p=0.031). Moreover, there was a significant association between preeclampsia and
      frequencies of allele HLA-DQB1*0602 (p<0.001), and genotypes of heterozygote
      (+0102/-0602) (p<0.001) and negative homozygote (-0102/-0602) (p=0.005). There
      also was an association between allele HLA-DQB1*0602 and preeclampsia in Fars
      ethnic group (p=0.028). Conclusion: It seems that immune incompatibility may have
      an important role in preeclampsia predisposition. According to our results, the
      lack of locus HLA-DQB1*0602 may be a risk factor for preeclampsia.

PMID- 29662966
TI  - Healthy eating index in women with polycystic ovary syndrome: A case-control
      study.
AB  - Background: Despite many effort to identify and control the factors involved in
      polycystic ovary syndrome (PCOS), there are no available reports indicating the
      association of healthy eating index (HEI) and PCOS. Objective: The present study
      has been conducted to examine the relationship between HEI and PCOS. Materials
      and Methods: In this case-control study, the study population comprised 297 women
      aged 20-40 yr referred to Baqiyatallah Hospital Clinics, Tehran, Iran in two
      groups: case group (n=99) and control group (n=198). The usual dietary data were
      collected using a validated 168-item semi-quantitative food frequency
      questionnaire. Standard anthropometric measurements (height, weight, and waist
      circumference) were also taken. Unconditional logistic regression was used to
      analyze the relationship between the PCOS and the HEI. Results: The mean age and
      body mass index of case and control groups were 29+/-5.5 vs. 29.5+/-6 yr and
      26.6+/-4.8 vs. 26+/-4.2 kg/m2, respectively (p=0.752, p=0.822). Mean HEI scores
      for the case and control groups were found to be 61 and 65, respectively. In
      final model and after adjustment for confounders, the prevalence of PCOS in
      subjects in the highest tertile HEI score was significantly (50%) less than those
      in the lowest tertile HEI score (OR=0.50; 95% CI: 0.25-0.74, p=0.001).
      Conclusion: Our results suggest that HEI score is inversely associated with the
      risk of PCOS in adult women.

PMID- 29662967
TI  - Maternal serum uric acid level and maternal and neonatal complications in
      preeclamptic women: A cross-sectional study.
AB  - Background: Preeclampsia is associated with maternal and neonatal complications.
      It has been indicated that increased uric acid might have a predictive role on
      preeclampsia. Objective: We aimed to investigate the relationship between the
      level of uric acid with maternal and neonatal complications in women with
      preeclampsia. Materials and Methods: In this cross-sectional study, 160 singleton
      preeclamptic women at more than 28 wk gestational age were included. Hemoglobin,
      hematocrit, platelet count, liver and uric acid tests, and maternal and neonatal
      complications were assessed. The severity of preeclampsia, placental abruption,
      preterm labor, thrombocytopenia, elevated alanine aminotransferase and aspartate
      aminotransferase (ALT and AST), HELLP syndrome, eclampsia and required
      hospitalization in the ICU was considered as the maternal complication. Fetal
      complications were: small for gestational age (SGA), intrauterine fetal death,
      hospitalization in the neonatal intensive care unit, and Apgar score <7 at five
      minutes. Results: Of our participants, 38 women had severe preeclampsia (23.8%).
      The mean level of uric acid in women with severe preeclampsia was significantly
      higher than non-severe preeclampsia (p=0.031), also in those with an abnormal
      liver test (p=0.009). The mean level of uric acid in women with preterm delivery
      was significantly higher than women with term delivery (p=0.0001). Also, the
      level of uric acid had no effect on neonatal hospitalization in neonate invasive
      care unit. Based on logistic regression, the incidence of severe preeclampsia not
      affected by decreased or increased serum levels of uric acid. Conclusion: With
      higher level of uric acid in server preeclampsia we can expected more
      complications such as hepatic dysfunction and preterm delivery. Thus serum uric
      acid measurement can be helpful marker for severe preeclampsia.

PMID- 29662968
TI  - Adnexal masses or perineural (tarlov) cysts? Differentiation by imaging
      techniques: A case report.
AB  - Background: Perineural cysts formed within the nerve-root sheath at the dorsal
      root ganglion. They are most commonly located in the arachnoid covering the
      junction of the dorsal ganglion and nerve root. They are usually asymptomatic,
      incidental findings, usually located in the lumbar and sacral region of the
      spinal canal. It is important to consolidate the imaging findings of this rare
      disease so clinicians can become more clinically relevant in the evaluation of
      these cysts. Case: Herein we report a case of perineural cyst misdiagnosed with
      hydrosalpinx by pelvic ultrasonography and finally diagnosed with magnetic
      resonance image. Conclusion: Perineural cyst should be considered, in the
      presence of bilateral adnexal masses separated from the ovaries in pelvic
      sonography.

PMID- 29662969
TI  - Research Volunteers' Attitudes Toward Chronic Fatigue Syndrome and Myalgic
      Encephalomyelitis.
AB  - Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS) are
      stigmatizing illnesses characterized by cognitive difficulties, post-exertional
      malaise, unrefreshing sleep, and other symptoms. Patients are often incapacitated
      and stigmatized as having a psychological disorder. The Chronic Fatigue Attitudes
      Test (CAT) assesses stigmatizing views toward individuals with Chronic Fatigue
      Syndrome, however, there is little research examining factors that may account
      for variation in stigmatizing attitudes toward this group. We examined CAT scores
      among college age research volunteers (N = 90), hypothesizing that exposure to
      information about ME and CFS as a result of volunteering on a ME and CFS-related
      research project would be associated with less stigmatizing attitudes compared to
      volunteers on unrelated projects. Findings indicated that ME and CFS research
      volunteers expressed less stigmatizing attitudes. Educational efforts aiming to
      disseminate accurate information about ME and CFS may mitigate stigma and the
      experience of stigma among individuals with ME and CFS.

PMID- 29662970
TI  - Does giving brief information keep patients calm during different oral surgical
      procedures?
AB  - OBJECTIVES: Dental anxiety may play a central role in the oral health status and
      treatment outcomes of oral surgical procedures. The study aimed to investigate
      the effect that brief written information has over patients undergoing oral
      surgical procedures and to evaluate factors that may cause anxiety. METHOD AND
      MATERIALS: A prospective study was performed on 38 mandibular third molar surgery
      patients (mean age 26.74 +/- 6.44 years) and 56 implant surgery patients (mean
      age 49.13 +/- 15.11 years). Each group was divided into two subgroups, and
      written information, explaining what they could expect and details about the
      procedure, was provided to study groups. The Spielberger State-Trait Anxiety
      Inventory was used to measure state (STAI-S) and trait anxiety (STAI-T). The
      visual analog scale (VAS) was used for pain scores preoperatively and on days 1,
      3, 5, and 7. Demographic data and intraoperative behaviors of patients were
      recorded. RESULTS: All groups had similar anxiety scores at baseline.
      Preoperative STAI-S and VAS scores were similar between study and control groups
      (P > .05). Study groups showed significantly lower mean intraoperative anxiety
      levels (P < .05). The implant group had a significantly lower VAS score (P <
      .05). STAI-T and preoperative STAI-S were not related to VAS. Postoperative STAI
      S and VAS and recuperation were correlated (P < .05). Women showed significantly
      higher anxiety and VAS scores. CONCLUSION: The patients who received written
      information did not report lower anxiety scores. However, improved patient
      cooperation could be achieved with this method. Different surgical procedures may
      cause anxiety for different reasons.

PMID- 29662971
TI  - Management of heat-induced bone necrosis following thermal removal of gutta
      percha.
AB  - Many endodontically treated teeth require a post to improve the retention of the
      coronal restoration, which necessitates removal of the coronal part of the gutta
      percha from the canal by thermal method, among other techniques. However, this
      technique carries the risk of heat conduction to the attachment unit of the
      periodontium and infliction of permanent damage especially in cases where the
      remaining root's dentin walls are thin. The overall objective of this article is
      to report on the clinical manifestations, histologic description, and periodontal
      management of three cases of heat-induced damage following thermal removal of
      gutta-percha.

PMID- 29662972
TI  - Implants placed simultaneously with maxillary sinus floor augmentation in the
      presence of antral pseudocysts: Presentation of a case series.
AB  - OBJECTIVE: To report the outcome of simultaneous placement of dental implants
      with maxillary sinus elevation in the presence of antral pseudocysts. METHOD AND
      MATERIALS: This case series involved 14 patients with 28 implants placed
      simultaneously with maxillary sinus elevation. The psuedocysts were treated by
      cystic fluid extraction. Postoperative examinations were performed at 3, 6, and
      12 months. RESULTS: All restorations were finished 6 to 9 months after implant
      placement. Nine antral pseudocysts disappeared and five decreased in size. All
      implants were deemed successful at 1 year postoperatively, showing
      osseointegration and masticatory function. No mobility was found during the
      follow-up period. CONCLUSION: In the absence of maxillary sinus infection, the
      combination of cystic fluid extraction, maxillary sinus elevation, and immediate
      implantation showed an acceptable clinical outcome in this series of patients.

PMID- 29662973
TI  - A novel approach to treat gingival recession and non-caries cervical lesion
      combined defects: Restoration guided creeping attachment (RGCA) technique. A case
      report.
AB  - Gingival recessions have multifactorial etiology and are often associated with
      non-caries cervical lesions. Different surgical techniques have been proposed
      over the years for their treatment, according to the severity of the recession. A
      novel technique, called restoration guided creeping attachment (RGCA), for the
      treatment of combined gingival recession and non-caries cervical lesion is
      presented. RGCA aims at treating Miller class I and II recessions using a
      specifically designed composite restoration and a minimally invasive approach. A
      clinical case describing the technique and forming the basis for further studies
      is presented. Although the results obtained are encouraging, a wider number of
      patients and longer follow-ups are needed to assess the reliability of this
      technique.

PMID- 29662974
TI  - Competition of cation-pi and exo-wall pi-pi interactions: a novel approach to
      achieve ultrasensitive response.
AB  - A novel approach to achieve ultrasensitive response was successfully developed by
      rationally introducing the competition between cation-pi and exo-wall pi-pi
      interactions into a pillar[5]arene-based supramolecular organogel (P5N-OG).
      Interestingly, the P5N-OG could be used for ion detection and separation,
      fluorescent display materials as well as ultrasensitive logic gates.

PMID- 29662975
TI  - Gene assembly via one-pot chemical ligation of DNA promoted by DNA
      nanostructures.
AB  - Current gene synthesis methods are driven by enzymatic reactions. Here we report
      the one-pot synthesis of a chemically-ligated gene from 14 oligonucleotides. The
      chemical ligation benefits from the highly efficient click chemistry approach
      templated by DNA nanostructures, and produces modified DNA that is compatible
      with polymerase enzymes.

PMID- 29662976
TI  - Self-templated synthesis of heavily nitrogen-doped hollow carbon spheres.
AB  - Nitrogen-doped hollow carbon spheres with a well-defined shape, uniform diameter,
      and high doping concentration (11 at%) are synthesized via space-confined thermal
      decomposition of a single source precursor zinc carbodiimide, which can serve as
      both carbon and nitrogen sources and also a self-template.

PMID- 29662978
TI  - Size-dependent uptake of electrically neutral amphipathic polymeric nanoparticles
      by cell-sized liposomes and an insight into their internalization mechanism in
      living cells.
AB  - Size-dependent uptake behaviors of electrically neutral amphipathic polymeric
      nanoparticles in cell-sized liposomes and living cells were investigated. Kinetic
      analyses and the particle size distribution suggested a size-dependent
      penetration mechanism (size threshold: 3.1 nm). The definite size-dependent
      uptake provides a new insight into the interactions between nanomaterials and
      living cells.

PMID- 29662977
TI  - Handheld skin printer: in situ formation of planar biomaterials and tissues.
AB  - We present a handheld skin printer that enables the in situ formation of
      biomaterial and skin tissue sheets of different homogeneous and architected
      compositions. When manually positioned above a target surface, the compact
      instrument (weight <0.8 kg) conformally deposits a biomaterial or tissue sheet
      from a microfluidic cartridge. Consistent sheet formation is achieved by
      coordinating the flow rates at which bioink and cross-linker solution are
      delivered, with the speed at which a pair of rollers actively translate the
      cartridge along the surface. We demonstrate compatibility with dermal and
      epidermal cells embedded in ionically cross-linkable biomaterials (e.g.,
      alginate), and enzymatically cross-linkable proteins (e.g., fibrin), as well as
      their mixtures with collagen type I and hyaluronic acid. Upon rapid crosslinking,
      biomaterial and skin cell-laden sheets of consistent thickness, width and
      composition were obtained. Sheets deposited onto horizontal, agarose-coated
      surfaces were used for physical and in vitro characterization. Proof-of-principle
      demonstrations for the in situ formation of biomaterial sheets in murine and
      porcine excisional wound models illustrate the capacity of depositing onto
      inclined and compliant wound surfaces that are subject to respiratory motion. We
      expect the presented work will enable the in situ delivery of a wide range of
      different cells, biomaterials, and tissue adhesives, as well as the in situ
      fabrication of spatially organized biomaterials, tissues, and biohybrid
      structures.

PMID- 29662979
TI  - Carbon dioxide bubble-propelled microengines in carbonated water and beverages.
AB  - We demonstrate a new type of gaseous fuel for rolled-up tubular Ti/Cr microengine
      powered by carbon dioxide microbubbles in carbonated water and brewed beverages.
      Existence of microbubble pockets is revealed using on-chip integrated transparent
      microtubes. Vertical position, angle of rotation and buoyancy of ferromagnetic
      Ti/Fe/Cr microengines are controlled using an external magnetic field.

PMID- 29662980
TI  - Continuous flow chemical vapour deposition of carbon nanotube sea urchins.
AB  - Hybrid structures consisting of functional materials enhanced by carbon nanotubes
      (CNTs) have potential for a variety of high impact applications, as shown by the
      impressive progress in sensing and mechanical applications enabled by CNT
      enhanced materials. The hierarchical organisation of CNTs with other materials is
      key to the design of macroscale devices benefiting from the unique properties of
      individual CNTs, provided CNT density, morphology and binding with other
      materials are optimized. In this paper, we provide an analysis of a continuous
      aerosol process to create a hybrid hierarchical sea urchin structure with CNTs
      organized around a functional metal oxide core. We propose a new mechanism for
      the growth of these carbon nanotube sea urchins (CNTSU) and give new insight into
      their chemical composition. To corroborate the new mechanism, we examine the
      influence of CNT growth conditions on CNTSU morphology and demonstrate a new in
      line characterisation technique to continuously monitor aerosol CNT growth during
      synthesis, which enables industrial-scale production optimization. Based upon the
      new formation mechanism we describe the first substrate-based chemical vapour
      deposition growth of CNTSUs which increases CNT length and improves G to D ratio,
      which also allows for the formation of CNTSU carpets with unique structures.

PMID- 29662981
TI  - Examination of inequivalent wetting on the crystal habit surfaces of RS-ibuprofen
      using grid-based molecular modelling.
AB  - Synthonic engineering tools, including grid-based searching molecular modelling,
      are applied to investigate the wetting interactions of the solute and four
      crystallisation solvents (ethanol, ethyl acetate, acetonitrile and toluene) with
      the {100}, {001} and {011} forms of RS-ibuprofen. The grid-based methods, in
      particular the construction of a crystal slab parallel to a given plane in a
      coordinate system with one axis perpendicular to the surface, are defined in
      detail. The interaction strengths and nature (dispersive, hydrogen bonding (H
      bonding) or coulombic forces) are related to the crystal growth rates and
      morphologies. The solute is found to interact strongest with the capping {011},
      then the side {001} and weakest with the top {100} habit surfaces. The solute
      interactions with the {100} and {001} surfaces are found to be almost solely
      dominated by dispersive force contributions, whilst the same with the {011}
      surfaces are found to have a greater contribution from H-bonding and coulombic
      forces. The increased surface rugosity, at the molecular level of the {011}
      surfaces, results in a favourable docking site in a surface 'valley', not present
      in the {100} and {001} surfaces. The H-bonding solvents ethanol, acetonitrile and
      ethyl acetate are found to strongly interact with the {011} surfaces and weakly
      with the {001} surfaces, with the {011} interactions having a much greater
      contribution from H-bonding and coulombic forces. The interaction energies of the
      apolar and aprotic solvent toluene, with the {011} and {001} surfaces, are found
      to be very close. Toluene is found having slightly stronger interactions with the
      {001} than the {011} surfaces, which are all dominated by dispersive
      interactions. The ratio of the average energy of the top 100 solvent interactions
      with the {001} surface divided by the average energy of the top 100 interactions
      with the {011} surface is compared to the ratio of the experimentally measured
      growth rates of the same forms. In general, the interaction energy ratio is found
      to have an inverse ratio with the growth rates, implying that the solvents which
      are calculated to interact strongly with a particular surface are impeding the
      growth of that surface and reducing the growth rate, in turn impacting upon the
      final morphology of the material.

PMID- 29662982
TI  - A novel spiro-annulated benzimidazole host for highly efficient blue
      phosphorescent organic light-emitting devices.
AB  - A novel host material featuring a spiro-annulated benzimidazole configuration is
      exploited for blue phosphorescent organic light-emitting devices (PhOLEDs). The
      new material exhibits a high triplet energy (3.07 eV) and a bipolar
      characteristic and is effective as the host for FIrpic-, FIr6- and FK306-based
      blue PhOLEDs with high performances.

PMID- 29662983
TI  - The recognition of glycans by protein receptors. Insights from NMR spectroscopy.
AB  - Carbohydrates (glycans, saccharides, sugars) are everywhere. In fact, glycan
      protein interactions are involved in many essential processes of life and
      disease. The understanding of the key structural details at the atomic and
      molecular level is of paramount importance to effectively design molecules for
      therapeutic purposes. Different approximations may be employed to decipher these
      molecular recognition processes with high resolution. Advances in cryo-electron
      microscopy are providing exquisite details on different biological mechanisms
      involving sugars, while better and better protocols for structural refinement in
      the application of X-ray methods for protein-sugar complexes and glycoproteins
      are also permitting fantastic advances in the glycoscience arena. Alternatively,
      NMR spectroscopy remains as one of the most rewarding techniques to explore
      protein-carbohydrate interactions. In fact, given the intrinsic dynamic nature of
      saccharides, NMR can afford exquisite structural information at the atomic
      detail, not accessible by other techniques. However, the access to this
      information is sometimes intricate, and requires careful analysis and well
      defined strategies. In this review, we have highlighted these issues and
      presented an overview of different modern NMR approaches with a focus on the
      latest developments and challenges.

PMID- 29662986
TI  - Discovery and characterization of natural products that act as pheromones in
      fish.
AB  - Covering: up to 2018 Fish use a diverse collection of molecules to communicate
      with conspecifics. Since Karlson and Luscher termed these molecules 'pheromones',
      chemists and biologists have joined efforts to characterize their structures and
      functions. In particular, the understanding of insect pheromones developed at a
      rapid pace, set, in part, by the use of bioassay-guided fractionation and natural
      product chemistry. Research on vertebrate pheromones, however, has progressed
      more slowly. Initially, biologists characterized fish pheromones by screening
      commercially available compounds suspected to act as pheromones based upon their
      physiological function. Such biology-driven screening has proven a productive
      approach to studying pheromones in fish. However, the many functions of fish
      pheromones and diverse metabolites that fish release make predicting pheromone
      identity difficult and necessitate approaches led by chemistry. Indeed, the few
      cases in which pheromone identification was led by natural product chemistry
      indicated novel or otherwise unpredicted compounds act as pheromones. Here, we
      provide a brief review of the approaches to identifying pheromones, placing
      particular emphasis on the promise of using natural product chemistry together
      with assays of biological activity. Several case studies illustrate bioassay
      guided fractionation as an approach to pheromone identification in fish and the
      unexpected diversity of pheromone structures discovered by natural product
      chemistry. With recent advances in natural product chemistry, bioassay-guided
      fractionation is likely to unveil an even broader collection of pheromone
      structures and enable research that spans across disciplines.

PMID- 29662987
TI  - A supramolecular assembly enables discrimination between metalloproteins and non
      metalloproteins.
AB  - Discriminating proteins using simple methods is a highly ambitious task. Herein,
      we provide the first report of a cyclodextrin based supramolecular host-guest
      assembly, which without involving any specially designed receptor and transducer,
      yields a distinct fluorescence response i.e., turn-on response towards non
      metalloproteins and turn-off response towards metalloproteins, and leads to their
      detection and discrimination.

PMID- 29662988
TI  - Polyvinyl alcohol-boronate gel for sodium hydroxide extraction.
AB  - Gels formed from commercially available polyvinyl alcohol (PVA) and 1,4-benzene
      diboronic acid (BdBA) in DMSO absorb NaOH efficiently from a bulk aqueous
      solution decreasing its pH.

PMID- 29662989
TI  - Group 3 metal trihalide complexes with neutral N-donor ligands - exploring their
      affinity towards fluoride.
AB  - Fluorination of [ScCl3(Me3-tacn)] (Me3-tacn = 1,4,7-trimethyl-1,4,7
      triazacyclononane) and [ScCl3(BnMe2-tacn)] (BnMe2-tacn = 1,4-dimethyl-7-benzyl
      1,4,7-triazacyclononane) by Cl/F exchange with 3 mol. equiv. of anhydrous [NMe4]F
      in CH3CN solution yields the corresponding [ScF3(R3-tacn)] (R3 = Me3 or BnMe2).
      These are the first examples of scandium fluoride complexes containing neutral co
      ligands. The fluorination occurs stepwise, and using a deficit of [NMe4]F
      produced [ScF2Cl(Me3-tacn)]. Attempts to fluorinate [YCl3(Me3-tacn)], [YI3(Me3
      tacn)], [LaCl3(Me3-tacn)(OH2)] or [MCl3(terpy)] (M = Sc, Y or La; terpy =
      2,2':6'2''-terpyridyl) using a similar method were unsuccessful, due to the Cl/F
      exchange being accompanied by loss of the neutral ligand from the metal centre.
      Fluorination of [ScCl3(Me3-tacn)] or [ScCl3(terpy)] with Me3SnF was also
      successful. The products were identified as the very unusual heterobimetallic
      [Sc(Me3-tacn)F2(MU-F)SnMe3Cl] and [Sc(terpy)F(MU-F)2(SnMe3Cl)2], in which the
      Me3SnCl formed in the reaction behaves as a weak Lewis acid towards the scandium
      fluoride complex, linked by Sc-F-Sn bridges. [Sc(terpy)F(MU-F)2(SnMe3Cl)2]
      decomposes irreversibly in solution but, whilst multinuclear NMR data show that
      [Sc(Me3-tacn)F2(MU-F)SnMe3Cl] is dissociated into the [ScF3(Me3-tacn)] and
      Me3SnCl in CH3CN solution, the bimetallic complex reforms upon evaporation of the
      solvent. The new scandium fluoride complexes and the chloride precursors have
      been characterised by microanalysis, IR and multinuclear NMR (1H, 19F, 45Sc)
      spectroscopy as appropriate. X-ray crystal structures provide unambiguous
      evidence for the identities of [Sc(Me3-tacn)F2(MU-F)SnMe3Cl], [ScF2Cl(Me3-tacn)],
      [YI3(Me3-tacn)], [{YI2(Me3-tacn)}2(MU-O)], [ScCl3(terpy)], [YCl3(terpy)(OH2)],
      and [{La(terpy)(OH2)Cl2}2(MU-Cl)2]. Once formed, the [ScF3(R3-tacn)] complexes
      are stable in water and unaffected by a ten-fold excess of Cl- or MeCO2-,
      although they are immediately decomposed by excess F-. The potential use of
      [ScF3(R3-tacn)] type complexes as platforms for 18F PET (positron emission
      tomography) radiopharmaceuticals is briefly discussed. Attempts to use the Group
      3 fluoride "hydrates", MF3.xH2O, as precursors were unsuccessful; no reaction
      with R3-tacn or terpy occurred either on reflux in CH3CN or under hydrothermal
      conditions (H2O, 180 degrees  C, 15 h). PXRD data showed that these "hydrates"
      actually contain the anhydrous metal trifluorides with small amounts of surface
      or interstitial water.

PMID- 29662990
TI  - Photophysical characterization of a highly luminescent divalent-europium
      containing azacryptate.
AB  - We report a new luminescent EuII-containing complex. The complex is excited with
      visible light, leading to emission centered at 447 nm with a lifetime of 1.25
      MUs. Computational studies suggest that the steric bulk of the ligand is a major
      factor influencing the wavelength of emission.

PMID- 29662993
TI  - Conformationally-restricted bicarbazoles with phenylene bridges displaying deep
      blue emission and high triplet energies: systematic structure-property
      relationships.
AB  - The synthesis is reported of twelve new symmetrical carbazole dimers in which the
      carbazole units are linked via 1,4-phenylene spacers. There are two distinct
      series of compounds based on the position on the carbazole ring where the
      phenylene spacer is attached: this is either at carbazole C(3) (series 1a-1f) or
      at C(2) (series 2a-2f). The central phenylene ring is substituted with either two
      methyl, two methoxy or two cyano substituents which impart an intramolecular
      torsional angle between the phenylene and carbazole rings, thereby limiting the
      extent of pi-conjugation between the carbazole units, and raising the triplet
      energies of the molecules to ET 2.6-3.0 eV, as determined from their
      phosphorescence spectra at 80 K. Structure-property relationships were studied by
      UV-vis and fluorescence spectroscopy, cyclic voltammetry and theoretical
      calculations. A notable observation is that substitution at the 2-position of
      carbazole (linear conjugation) exerts control over the position of the HOMO,
      while substitution at the 3-position of carbazole (meta conjugation) allows
      greater control over the LUMO. X-ray crystal structures are reported for two of
      the bicarbazoles. Compound 2d is shown to be a suitable host for the sky-blue
      emitter FIrpic in PhOLEDs, with improved device performance compared to CBP as
      host.

PMID- 29662995
TI  - Direct observation of stepwise intermolecular proton and hydrogen transfer
      between alcohols and the triplet state of 4-nitro-1-naphthol.
AB  - Solvent assisted excited state intramolecular proton or hydrogen transfer has
      received much attention in bi-functional molecules with hydrogen donating and
      hydrogen accepting groups. As a typical photoacid, 1-naphthol exhibits photo
      stable behavior in methanol; whether this would be disrupted by a bonded hydrogen
      accepting group contained in the molecule is still not assured. We present
      nanosecond transient absorption measurements relating to kinetics and the
      characteristic absorption of key intermediates upon the excitation of 4-nitro-1
      naphthol in alcoholic solutions, and also transient resonance Raman spectroscopy
      studies combined with theoretical calculations to identify the structures of
      these intermediates, and we reveal the reaction mechanism to be stepwise
      deprotonation, hydrogen abstraction and protonation. These results demonstrate
      that alcohol assisted intramolecular proton or hydrogen transfer cannot occur in
      this system, but that the solvent cluster plays an important role during such
      stepwise reactions.

PMID- 29662996
TI  - Light-fuelled reversible expansion of spiropyran-based vesicles in water.
AB  - We present the design and synthesis of spiropyran-based dynamic vesicles, for
      which the building block is the amphiphilic merocyanine isomer. Under irradiation
      with visible light, the photo-conversion of the protonated and charged
      merocyanine to the neutral spiropyran form leads to the transient and reversible
      expansion of these vesicles.

PMID- 29662997
TI  - Dative versus electron-sharing bonding in N-oxides and phosphane oxides R3EO and
      relative energies of the R2EOR isomers (E = N, P; R = H, F, Cl, Me, Ph). A
      theoretical study.
AB  - Quantum chemical calculations using ab initio methods at the CCSD(T)/def2-TZVPP
      level and density functional theory using BP86 and M06-2X functionals in
      conjunction with def2-TZVPP basis sets have been carried out on the title
      molecules. The calculated energies suggest that the N-oxides R3NO with R = F, Cl
      are lower in energy than the amine isomers R2NOR, but the latter form is more
      stable than the N-oxides when R = H, Me, Ph. In contrast, the phosphane oxides
      R3PO are always more stable than the phosphanyl isomers R2NOR except for the
      parent system with R = H, where the two isomers are close in energy. The energy
      decomposition analysis suggests that the best description of the N-O bond in N
      oxides R3NO depends on the nature of the substituent R. The halogen systems F3NO
      and Cl3NO and the triphenyl species Ph3NO possess dative bonds R3N->O, which are
      enhanced by R3N<-O pi backdonation. The contribution of the pi backdonation is
      only 10% of the total orbital interactions DeltaEorb in Ph3NO, but it amounts to
      ~22% of DeltaEorb in F3NO and Cl3NO. The N-O bonds H3NO and Me3NO are better
      described in terms of electron-sharing single bonds between charged fragments
      R3N+-O-, which are supported by modest R3N+<-O- pi backdonation that comprise 13
      16% of DeltaEorb. In contrast, all phosphane oxides R3PO are best depicted with
      electron-sharing single bonds between charged fragments R3P+-O-, which are
      significantly supported by R3P+<-O- pi backdonation contributing 22-32% of
      DeltaEorb.

PMID- 29662998
TI  - Engineering crystalline CoOOH anchored on an N-doped carbon support as a durable
      electrocatalyst for the oxygen reduction reaction.
AB  - Finding highly active, low-cost and stable electro-catalysts for the oxygen
      reduction reaction is challenging but crucial for several applications such as
      fuel cells and metal batteries. Herein, we report a novel electro-catalyst of
      crystalline CoOOH anchored on an N-doped carbon support through a facile method,
      and we explore its origin of activity via investigating the correlation between
      the composition of the catalyst and its electrochemical properties. Nitrogen is
      successfully incorporated into a carbon support, and CoOOH is desirably anchored
      on a carbon matrix forming Co-N coordination sites in the catalyst, which is
      revealed to be responsible for the much enhanced oxygen reduction activity
      compared to the oxygen reduction activities of the electrocatalysts having either
      single-doped nitrogen or anchored CoOOH species in a carbon support. Furthermore,
      it is deduced that the active sites for enhanced oxygen reduction can be
      attributed to Co-Nx, carbon atoms neighboring the doped nitrogen and even the
      CoOOH species. The optimized catalyst CoOOH@NC-175/300 shows lower onset
      potential and half-wave potential and much better cyclic stability compared to
      those of the state-of-the-art Pt/C catalysts. This novel finding provides a new
      approach for the rational engineering of low-cost, highly active and stable non
      precious ORR electrocatalysts for applications in energy conversion and storage.

PMID- 29662999
TI  - An unprecedented tandem synthesis of fluorescent coumarin-fused pyrimidines via
      copper-catalyzed cross-dehydrogenative C(sp3)-N bond coupling.
AB  - An efficient, one-pot Cu-catalyzed tandem synthesis of fluorescent 1-benzyl-2
      phenyl-1,2-dihydro-5H-chromeno[4,3-d]pyrimidin-5-ones from 4-chloro-3
      formylcoumarin and benzylamines was developed by in situ intramolecular cross
      dehydrogenative C(sp3)-N bond formation in moderate-to-good yields under ligand
      free ambient conditions. This synthesis was easily scalable, and the generality
      of the substrates was established. These coumarin-fused pyrimidines exhibited
      interesting photo-physical properties and high quantum yields, and would be
      potential candidates for facilitating suitable studies in medicinal chemistry and
      materials science.

PMID- 29663001
TI  - Bismuth(iii)-catalyzed cycloisomerization and (hetero)arylation of alkynols:
      simple access to 2-(hetero)aryl tetrahydrofurans and tetrahydropyrans.
AB  - 2-(Hetero)aryl tetrahydrofurans and tetrahydropyrans were successfully
      synthesized using Bi(OTf)3-catalyzed hydroalkoxylation (cycloisomerization) of
      alkynols (via 5 or 6 exo-dig cyclization) and intermolecular (hetero)arylation.
      This reaction involves a highly efficient cascade process, where initially the
      alkynol undergoes a cycloisomerization step via activation of the triple bond and
      generates the oxocarbenium ion, which subsequently participates in the
      (hetero)hydroarylation step with electron-rich arenes. Simple to complex suitably
      functionalized alkynols (4-pentyn-1-ols and 5-hexyn-1-ols) and electron-rich
      aromatic compounds were found to be reliable substrates in this cascade
      transformation and furnished a wide range of oxygen heterocycles. This practical
      tandem process provides a means to build libraries related to pharmacologically
      active molecules and natural product like scaffolds.

PMID- 29663000
TI  - Structure formation in soft nanocolloids: liquid-drop model.
AB  - Using a model where soft nanocolloids such as spherical polymer brushes and star
      polymers are viewed as compressible liquid drops, we theoretically explore
      contact interactions between such particles. By numerically minimizing the
      phenomenological free energy consisting of bulk and surface terms, we find that
      at small deformations the drop-drop interaction is pairwise additive and
      described by a power law. We also propose a theory to describe the small
      deformation regime, and the agreement is very good at all drop compressibilities.
      The large-deformation regime, which is dominated by many-body interactions, is
      marked by a rich phase diagram which includes the face- and body-centered-cubic,
      sigma, A15, and simple hexagonal lattice as well as isostructural and re-entrant
      transitions. Most of these features are directly related to the non-convex
      deformation free energy emerging from many-body effects in the partial-faceting
      regime. The phase diagram, which depends on just two model parameters, contains
      many of the condensed phases observed in experiments. We also provide statistical
      mechanical arguments that relate the two model parameters to the molecular
      architecture of the polymeric nanocolloids, chain rigidity, and solvent quality.
      The model represents a generic framework for the overarching features of the
      phase behavior of polymeric nanocolloids at high compressions.

PMID- 29663002
TI  - "Patterning with loops" to dynamically reconfigure polymer gels.
AB  - The structural and mechanical properties of gels can be controlled by promoting
      the unfolding (and refolding) of loops (stored lengths) embedded within the
      networks. As a loop unfolds, the released chain length can increase the
      extensibility and reconfigurability of the gel. Here, we develop a theoretical
      model that couples the elasticity of the gel to the dynamic transitions occurring
      in loops that lie between the crosslinks. Using this model, we show that a
      thermally-induced swelling of the gel generates an internal strain, which unfolds
      the loops and thereby further increases the degree of gel swelling. We exploit
      this cooperative behavior to reconfigure the gel by patterning the location of
      the loops within the sample. Through this approach, we convert flat, two
      dimensional layers into three-dimensional forms and introduce architectural
      features into uniform 3D slabs. At a fixed temperature, an applied force produces
      analogous structural transformations. The shape-changes are reversible: the
      systems return to their original structure when the temperature is reset or the
      force is removed. The findings provide guidelines for creating materials that
      interconvert thermal, chemical and mechanical energy to perform work. Such
      systems could be useful for designing soft robotic materials that convert
      environmental stimuli into useful functionality.

PMID- 29663003
TI  - The evolution of artificial light actuators in living systems: from planar to
      nanostructured interfaces.
AB  - Artificially enhancing light sensitivity in living cells allows control of
      neuronal paths or vital functions avoiding the wiring associated with the use of
      stimulation electrodes. Many possible strategies can be adopted for reaching this
      goal, including the direct photoexcitation of biological matter, the genetic
      modification of cells or the use of opto-bio interfaces. In this review we
      describe different light actuators based on both inorganic and organic
      semiconductors, from planar abiotic/biotic interfaces to nanoparticles, that
      allow transduction of a light signal into a signal which in turn affects the
      biological activity of the hosting system. In particular, we will focus on the
      application of thiophene-based materials which, thanks to their unique chemical
      physical properties, geometrical adaptability, great biocompatibility and
      stability, have allowed the development of a new generation of fully organic
      light actuators for in vivo applications.

PMID- 29663004
TI  - Synchronization in pairs of rotating active biomotors.
AB  - Although synchronization is a well-known physical phenomenon, experimental
      studies of its emergence in living bacterial cells are still scarce. The
      difficulty in generating a controlled scenario to detect synchronization has
      limited the experimental outcomes so far. We present a realization based on
      holographic optical tweezers in which adhered pairs of self-propelled bacteria
      rotate in a plane. The separation distance between the bacteria determines the
      strength of the hydrodynamic coupling. Despite the noisy environment and
      autonomous dynamics of the living bacteria, we find evidence of phase locking and
      frequency entrainment in their rotation. The observation of higher order
      frequency synchronization is also discussed.

PMID- 29663005
TI  - Alkali-induced crumpling of Ti3C2Tx (MXene) to form 3D porous networks for sodium
      ion storage.
AB  - We present a novel strategy for constructing three-dimensional (3D) porous
      Ti3C2Tx (MXene) networks by alkali-induced crumpling of Ti3C2Tx nanosheets. The
      3D porous Ti3C2Tx networks display high capacity and outstanding rate performance
      as anode materials for sodium-ion batteries.

PMID- 29663006
TI  - Silicon compatible Sn-based resistive switching memory.
AB  - Large banks of cheap, fast, non-volatile, energy efficient, scalable solid-state
      memories are an increasingly essential component for today's data intensive
      computing. Conductive-bridge random access memory (CBRAM) - which involves
      voltage driven formation and dissolution of Cu or Ag filaments in a Cu (or Ag)
      anode/dielectric (HfO2 or Al2O3)/inert cathode device - possesses the necessary
      attributes to fit the requirements. Cu and Ag are, however, fast diffusers and
      known contaminants in silicon microelectronics. Herein, employing a criterion for
      electrode metal selection applicable to cationic filamentary devices and using
      first principles calculations for estimating diffusion barriers in HfO2, we
      identify tin (Sn) as a rational, silicon CMOS compatible replacement for Cu and
      Ag anodes in CBRAM devices. We then experimentally fabricate Sn based CBRAM
      devices and demonstrate very fast, steep-slope memory switching as well as
      threshold switching, comparable to Cu or Ag based devices. Furthermore, time
      evolution of the cationic filament formation along with the switching mechanism
      is discussed based on time domain measurements (I vs. t) carried out under
      constant voltage stress. The time to threshold is shown to be a function of both
      the voltage stress (Vstress) as well as the initial leakage current (I0) through
      the device.

PMID- 29663007
TI  - Electrochemical amphotericity and NIR absorption induced via the step-wise
      protonation of fused quinoxaline-tetrathiafulvalene-pyrroles.
AB  - We describe an effective approach to producing electrochemical amphoteric
      character and tuning optical properties. Reversible step-wise protonation of
      quinoxaline annulated TTF-pyrrole derivatives promotes intramolecular electron
      transfer and leads to formation of stable, fully charge-separated diradical
      states. This allows for the creation of low bandgap systems and NIR optical
      properties.

PMID- 29663008
TI  - Metabolite amyloid-like fibrils interact with model membranes.
AB  - Amyloid-like structure formation by various metabolites represents a significant
      extension of the amyloidogenic building block family. Similar to protein
      amyloids, metabolite amyloids induce apoptotic toxicity, a process that was
      linked to membrane association. Here, we demonstrate that metabolite amyloids
      interact with model membranes and study the mechanism by molecular dynamics.

PMID- 29663009
TI  - Exploring time-resolved photoluminescence for nanowires using a three-dimensional
      computational transient model.
AB  - Time-resolved photoluminescence (TRPL) has been implemented experimentally to
      measure the carrier lifetime of semiconductors for decades. For the
      characterization of nanowires, the rich information embedded in TRPL curves has
      not been fully interpreted and meaningfully mapped to the respective material
      properties. This is because their three-dimensional (3-D) geometries result in
      more complicated mechanisms of carrier recombination than those in thin films and
      analytical solutions cannot be found for those nanostructures. In this work, we
      extend the intrinsic power of TRPL by developing a full 3-D transient model,
      which accounts for different material properties and drift-diffusion, to simulate
      TRPL curves for nanowires. To show the capability of the model, we perform TRPL
      measurements on a set of GaAs nanowire arrays grown on silicon substrates and
      then fit the measured data by tuning various material properties, including
      carrier mobility, Shockley-Read-Hall recombination lifetime, and surface
      recombination velocity at the GaAs-Si heterointerface. From the resultant TRPL
      simulations, we numerically identify the lifetime characteristics of those
      material properties. In addition, we computationally map the spatial and temporal
      electron distributions in nanowire segments and reveal the underlying carrier
      dynamics. We believe this study provides a theoretical foundation for
      interpretation of TRPL measurements to unveil the complex carrier recombination
      mechanisms in 3-D nanostructured materials.

PMID- 29663010
TI  - Septo-optic Dysplasia : Assessment of Associated Findings with Special Attention
      to the Olfactory Sulci and Tracts.
AB  - PURPOSE: Septo-optic dysplasia is a congenital disorder consisting of optic nerve
      hypoplasia and absent septum pellucidum. While associated anomalies have been
      described, olfactory sulcus and bulb-tract hypoplasia have been scantily reported
      and was the focus of this study. METHODS: The picture archival and communications
      system and radiology information system (PACS-RIS) was searched over 15 years for
      patients with suspected septo-optic dysplasia (n = 41) and cerebral magnetic
      resonance imaging (MRI). Included patients had coronal (<=3 mm), axial (<=4 mm),
      and sagittal (<=4 mm) imaging reviewed by two staff neuroradiologists by
      consensus. Both olfactory sulcus and bulb-tract hypoplasia were ascribed a grade
      of 0 (normal) to 3 (complete hypoplasia). Other associated congenital anomalies
      were recorded, if present. Incidence of anomalies were compared to age-matched
      and gender-matched control patients. RESULTS: Out of 41 septo-optic dysplasia
      patients 33 were included (mean age = 120.7 months), with 8 excluded due to
      isolated septum pellucidum absence (n = 5), isolated bilateral optic hypoplasia
      (n = 2), or inadequate imaging (n = 1). An olfactory sulcus was hypoplastic on
      one or both sides in 14/33 (42.4%). Olfactory bulb hypoplasia was noted in one or
      both tracts in 15/33 (45.4%). A significant correlation was found between degree
      of olfactory sulcal and bulb-tract hypoplasia (rho = 0.528, p = 0.0009). Other
      anomalies were: anterior falx dysplasia (n = 16, 48.5%), incomplete hippocampal
      inversion (n = 14, 42.4%), polymicrogyria (n = 11, 33.3%), callosal complete or
      partial agenesis (n = 10, 30.3%), schizencephaly (n = 8, 24.2%), ectopic
      posterior pituitary (n = 6, 18.2%), and nodular heterotopia (n = 4, 12.1%). Of
      the age-matched control patients 10/33 (30.3%) had at least mild anterior falx
      hypoplasia, and 1 control patient was noted to have unilateral incomplete
      hippocampal inversion (IHI); none of the age-matched control patients had
      olfactory sulcus or bulb-tract hypoplasia. CONCLUSION: Olfactory sulcus and bulb
      tract hypoplasia are fairly common in septo-optic dysplasia and can be discordant
      between sides. Of the other associated anomalies, anterior falx dysplasia seems
      to be the most common.

PMID- 29663012
TI  - Medial joint line elevation of the tibia measured during surgery has a
      significant correlation with the limb alignment changes following medial
      unicompartmental knee arthroplasty.
AB  - PURPOSE: This study aimed to determine the correlation between the change in
      joint line height calculated from the resected bone and insert thickness during
      surgery and the change in limb alignment following unicompartmental knee
      arthroplasty (UKA). It was hypothesized that joint line elevation is correlated
      with the change in limb alignment. METHODS: A total of 74 consecutive patients
      diagnosed with either isolated medial compartmental osteoarthritis (38 patients)
      or spontaneous osteonecrosis of the knee (36 patients) were included. The
      thickness of the proximal tibial and distal femoral bony cuts was measured during
      surgery; using these values, the medial joint line elevation of the tibia (MJLET)
      and medial joint line reduction of the femur (MJLRF) were defined. The
      correlation between the amount of change in the hip-knee-ankle (HKA) angle before
      and after surgery (deltaHKA) and the thickness of the tibial insert (TI), MJLET,
      or MJLRF were evaluated. RESULTS: The mean values of deltaHKA, TI, MJLET, and
      MJLRF were 5.0 degrees  +/- 2.6 degrees , 8.5 +/- 0.8, 4.4 +/- 1.3, and 0.0 +/-
      1.1 mm, respectively. The deltaHKA had a significant, but weak-positive
      correlation with the TI (P = 0.02), and moderate-positive correlation with MJLET
      (P < 0.001). However, no correlation was observed between deltaHKA and MJLRF.
      CONCLUSIONS: The MJLET measured during surgery had a significant moderate
      positive correlation with the change in limb alignment following medial UKA. For
      clinical relevance, the surgeon can predict postoperative limb alignment after
      UKA by considering, intraoperatively, both the insert thickness and the depth of
      resection at the proximal tibia thus minimizing technical error to obtain an
      optimal alignment after UKA. LEVEL OF EVIDENCE: Diagnostic study, level II.

PMID- 29663011
TI  - Plasma branched chain/aromatic amino acids, enriched Mediterranean diet and risk
      of type 2 diabetes: case-cohort study within the PREDIMED Trial.
AB  - AIMS/HYPOTHESIS: Branched-chain amino acids (BCAAs) and aromatic amino acids
      (AAAs) are associated with type 2 diabetes. However, repeated measurements of
      BCAA/AAA and their interactions with dietary interventions have not been
      evaluated. We investigated the associations between baseline and changes at 1
      year in BCAA/AAA with type 2 diabetes in the context of a Mediterranean diet
      (MedDiet) trial. METHODS: We included 251 participants with incident type 2
      diabetes and a random sample of 694 participants (641 participants without type 2
      diabetes and 53 overlapping cases) in a case-cohort study nested within the
      PREvencion con DIeta MEDiterranea (PREDIMED) trial. Participants were randomised
      to a MedDiet+extra-virgin olive oil (n = 273), a MedDiet+nuts (n = 324) or a
      control diet (n = 295). We used LC-MS/MS to measure plasma levels of amino acids.
      Type 2 diabetes was a pre-specified secondary outcome of the PREDIMED trial.
      RESULTS: Elevated plasma levels of individual BCAAs/AAAs were associated with
      higher type 2 diabetes risk after a median follow-up of 3.8 years: multivariable
      HR for the highest vs lowest quartile ranged from 1.32 for phenylalanine ([95% CI
      0.90, 1.92], p for trend = 0.015) to 3.29 for leucine ([95% CI 2.03, 5.34], p for
      trend<0.001). Increases in BCAA score at 1 year were associated with higher type
      2 diabetes risk in the control group with HR per SD = 1.61 (95% CI 1.02, 2.54),
      but not in the MedDiet groups (p for interaction <0.001). The MedDiet+extra
      virgin olive oil significantly reduced BCAA levels after 1 year of intervention
      (p = 0.005 vs the control group). CONCLUSIONS/INTERPRETATION: Our results support
      that higher baseline BCAAs and their increases at 1 year were associated with
      higher type 2 diabetes risk. A Mediterranean diet rich in extra-virgin olive oil
      significantly reduced the levels of BCAA and attenuated the positive association
      between plasma BCAA levels and type 2 diabetes incidence. Clinical trial number:
      SRCTN35739639 ( www.controlled-trials.com ).

PMID- 29663013
TI  - Bone-to-bone integrations were complete within 5 months after anatomical
      rectangular tunnel anterior cruciate ligament reconstruction using a bone
      patellar tendon-bone graft.
AB  - PURPOSE: Anterior cruciate ligament (ACL) reconstruction using a bone-patellar
      tendon-bone (BTB) graft is known to provide secure fixation due to the direct
      bone-to-bone integration of the bone plug and bone tunnel. It is important to
      know the time required for bone integration when designing the postoperative
      rehabilitation protocol or deciding when the patient can return to competition
      level activity, especially if the patient is an athlete. However, because reports
      are scarce, the period necessary for bone-to-bone integration after ACL
      reconstruction using a BTB graft remains unclear. The purpose of this study was
      to clarify this issue. It was hypothesised that ACL reconstruction using a BTB
      graft via an anatomical rectangular tunnel would help in the integration between
      bone plugs and bone tunnels on both the femoral and tibial sides after at least 6
      months, at which point basic exercises similar to pre-injury sporting activity
      levels can be resumed. METHODS: This study included 40 knees treated with ACL
      reconstruction using a BTB graft via anatomical rectangular tunnel reconstruction
      between 2013 and 2014 in a single institute. The integration between bone plugs
      and bone tunnels was evaluated using multi-slice tomosynthesis, which is a
      technique for producing slice images using conventional radiographic systems, at
      1, 3, and 5 months postoperatively. All procedures were performed by two
      experienced surgeons. Bone integration was evaluated by two orthopaedic doctors.
      RESULTS: The rates of integration of the bone plug and femoral bone tunnel on
      tomosynthesis at 1, 3, and 5 months postoperatively were 0, 55, and 100%,
      respectively. On the tibial side, the corresponding rates were 0, 75, and 100%,
      respectively. The rate of integration on the tibial side was significantly higher
      than that on the femoral side at 3 months postoperatively (p = 0.031).
      CONCLUSIONS: Bone-to-bone integration on the femoral and tibial sides was
      complete within 5 months after surgery in all cases. Since the time required for
      bone integration is important in designing the postoperative rehabilitation
      approach, these results will serve as a useful guideline for planning
      rehabilitation protocols. LEVEL OF EVIDENCE: IV.

PMID- 29663014
TI  - Prediction and diagnosis of interval metastasis after neoadjuvant
      chemoradiotherapy for oesophageal cancer using 18F-FDG PET/CT.
AB  - OBJECTIVE: During neoadjuvant chemoradiotherapy for oesophageal cancer, or in the
      interval prior to surgery, some patients develop systemic metastasis. This study
      aimed to evaluate the diagnostic performance of 18F-FDG PET/CT for the detection
      of interval metastasis and to identify predictors of interval metastases in a
      large cohort of oesophageal cancer patients. METHODS: In total, 783 consecutive
      patients with potentially resectable oesophageal cancer who underwent
      chemoradiotherapy and pre- and post-treatment 18F-FDG PET/CT between 2006 and
      2015 were analyzed from a prospectively maintained database. Diagnostic accuracy
      measures were calculated on a per-patient basis using histological verification
      or clinical follow-up as a reference standard. Multivariable logistic regression
      analysis was performed to determine pre-treatment predictors of interval
      metastasis. A prediction score was developed to predict the probability of
      interval metastasis. RESULTS: Of 783 patients that underwent 18F-FDG PET/CT
      restaging, 65 (8.3%) were found to have interval metastasis and 44 (5.6%) were
      deemed to have false positive lesions. The resulting sensitivity and specificity
      was 74.7% (95% CI: 64.3-83.4%) and 93.7% (95% CI: 91.6-95.4%), respectively.
      Multivariable analysis revealed that tumor length, cN status, squamous cell tumor
      histology, and baseline SUVmax were associated with interval metastasis. Based on
      these criteria, a prediction score was developed with an optimism adjusted C
      index of 0.67 that demonstrated accurate calibration. CONCLUSIONS: 18F-FDG PET/CT
      restaging detects distant interval metastases in 8.3% of patients after
      chemoradiotherapy for oesophageal cancer. The provided prediction score may
      stratify risk of developing interval metastasis, and could be used to prioritize
      additional restaging modalities for patients most likely to benefit.

PMID- 29663015
TI  - [Palliative care : Challenges in the intensive care unit].
AB  - Intensive care unit (ICU) stays often result due to an acute, potentially life
      threatening illness or aggravation of a chronic life-threatening illness. In many
      cases, ICU patients die after life-sustaining treatments are withdrawn or
      withheld. When patients are asked, they prefer to die at home, although logistic
      and medical problems often prevent this. Therefore, attention focuses on care at
      the end of life in the ICU. Despite many efforts to improve the quality of care,
      evidence suggests that the quality in hospitals varies significantly and that
      palliative care in the ICU has not significantly improved over time. In this
      review, aspects of palliative care that are specific to ICU patients are
      discussed.

PMID- 29663016
TI  - Gallic acid, a phenolic compound isolated from Mimosa bimucronata (DC.) Kuntze
      leaves, induces diuresis and saluresis in rats.
AB  - Although present in the leaves of Mimosa bimucronata (DC.) and many other
      medicinal plants commonly used to augment urinary volume excretion, the effects
      of gallic acid as a diuretic agent remain to be studied. Wistar rats were orally
      treated with vehicle, hydrochlorothiazide, or gallic acid. The effects of gallic
      acid in the presence of hydrochlorothiazide, furosemide, amiloride, L-NAME,
      atropine, and indomethacin were also investigated. Diuretic index, pH,
      conductivity, and electrolyte excretion were evaluated at the end of the
      experiment (after 8 or 24 h). Gallic acid induced diuretic and saluretic (Na+ and
      Cl-) effects, without interfering with K+ excretion, when orally given to female
      and male rats at a dose of 3 mg/kg. These effects were associated with increased
      creatinine and conductivity values while pH was unaffected by any of the
      treatments. Plasma Na+, K+, and Cl- levels were not affected by any of the acute
      treatments. The combination with hydrochlorothiazide or furosemide was unable to
      intensify the effects of gallic acid when compared with the response obtained
      with each drug alone. On the other hand, the treatment with amiloride plus gallic
      acid amplified both diuresis and saluresis, besides to a marked potassium-sparing
      effect. Its diuretic action was significantly prevented in the presence of
      indomethacin, a cyclooxygenase inhibitor, but not with the pretreatments with L
      NAME or atropine. Although several biological activities have already been
      described for gallic acid, this is the first study demonstrating its potential as
      a diuretic agent.

PMID- 29663018
TI  - Effects of acute morphine withdrawal on ultrasonic vocalizations in adult rats:
      unchanged 50-kHz call rate and altered subtype profile.
AB  - RATIONALE: Adult rat 22- and 50-kHz ultrasonic vocalizations (USVs) are commonly
      considered as indices of negative and positive affect, respectively. More
      specifically, we have proposed that positive affective states are revealed by a
      predominance of trill over flat 50-kHz call subtypes. However, the 50-kHz call
      subtypes emitted during aversive drug states remain largely uninvestigated.
      OBJECTIVES: To determine whether acute morphine withdrawal affects 50-kHz call
      rates or alters the relative prevalence of trill and flat calls. METHODS: In
      experiment 1, adult male rats were given saline or morphine (6 mg/kg SC), then
      acutely challenged 4 h later with saline or naloxone (1 mg/kg SC), and recorded
      10-30 min post-injection. In experiments 2 and 3, rats received saline or
      morphine (6 mg/kg), followed 4 h later by acute saline or naloxone (0.1 mg/kg)
      challenge; USVs were subsequently recorded during 30-min place conditioning
      sessions. RESULTS: Naloxone (0.1 mg/kg) produced a strong conditioned place
      aversion only after acute morphine pretreatment, consistent with antagonist
      precipitated morphine withdrawal. The morphine-naloxone combination decreased the
      relative prevalence of trills and promoted flat calls. Naloxone given alone (0.1
      and 1 mg/kg) inhibited trill calls but did not significantly alter the prevalence
      of flat calls, whereas morphine given alone (4 h pre-session) was largely without
      effect. Fifty-kHz call rates were inhibited by naloxone given alone, but
      otherwise unaffected. Twenty-two-kHz calls were sparse. CONCLUSIONS: The 50-kHz
      call subtype shift seen during antagonist-precipitated morphine withdrawal was
      opposite in direction to that previously associated with rewards, and hence may
      reveal negative affect.

PMID- 29663019
TI  - [Retrieval of a migrated plastic stent in a 51-year-old man].
AB  - BACKGROUND: Endosonographically guided transgastric drainage is the first-line
      interventional therapy of walled-off necrosis and symptomatic pancreatic
      pseudocysts in necrotizing pancreatitis. Plastic stents or lumen apposing metal
      stents are commonly used. A possible complication of endoscopic therapy is stent
      migration. CASE REPORT: We report upon a 51-year-old man who presented with acute
      necrotizing pancreatitis. Transgastric necrosectomy was performed and 5
      transmural double-pigtail stents (DPS) were left in situ to drain the residual
      retroperitoneal cavity. The patient recovered and 4 stents were endoscopically
      removed 5 weeks later on an outpatient basis, whereas the fifth stent was
      suspected to have passed spontaneously via the natural route. The asymptomatic
      patient presented 3 months later for follow-up computed tomography. The necrosis
      had healed but one DPS was seen beyond the gastric wall near the kidney.
      Transmural access to the stent could be achieved by an endosonographically guided
      puncture toward the proximal portion of the stent followed by placement of a
      hydrophilic guidewire alongside the stent. A new gastrostomy was created by using
      a 6F cystotome followed by wire-guided dilation with a 12 mm balloon. The stent
      could then be grasped with transmurally inserted rat-tooth forceps and
      repositioned across the gastrostomy site. The patient was given prophylactic
      antibiotics. After removal of the stent, the patient could be discharged.
      CONCLUSION: Herein, we present the successful endosonographically guided
      transmural removal of a retroperitoneally migrated plastic stent. Of note, in our
      patient we had to rely completely on endosonography and radiography for
      localization and targeting of the stent, since the former necrotic cavity had
      meanwhile completely healed.

PMID- 29663017
TI  - Cyclic nucleotide phosphodiesterases: potential therapeutic targets for alcohol
      use disorder.
AB  - Alcohol use disorder (AUD), which combines the criteria of both alcohol abuse and
      dependence, contributes as an important causal factor to multiple health and
      social problems. Given the limitation of current treatments, novel medications
      for AUD are needed to better control alcohol consumption and maintain abstinence.
      It has been well established that the intracellular signal transduction mediated
      by the second messengers cyclic AMP (cAMP) and cyclic GMP (cGMP) crucially
      underlies the genetic predisposition, rewarding properties, relapsing features,
      and systemic toxicity of compulsive alcohol consumption. On this basis, the
      upstream modulators phosphodiesterases (PDEs), which critically control
      intracellular levels of cyclic nucleotides by catalyzing their degradation, are
      proposed to play a role in modulating alcohol abuse and dependent process. Here,
      we highlight existing evidence that correlates cAMP and cGMP signal cascades with
      the regulation of alcohol-drinking behavior and discuss the possibility that PDEs
      may become a novel class of therapeutic targets for AUD.

PMID- 29663021
TI  - [Willingness to participate in group beneficial dementia research].
AB  - BACKGROUND: With the fourth Act on the amendment of pharmaceutical legal and
      other regulations it became law in Germany from the beginning of 2017 that under
      certain conditions, pharmaceutical research will be allowed with persons
      incapable of giving consent, even if this research may only be beneficial to
      other sufferers of the same disease, i. e. group beneficial research. OBJECTIVE:
      We conducted a semistructured, non-representative survey among psychiatric
      patients and their relatives. PARTICIPANTS AND METHODS: This survey was done for
      a period of 3 months until the end of September 2017 in the practice of M. H.
      with successively examined patients and their relatives. Patients incapable of
      giving consent related to dementia, depression and emergency cases, were
      excluded. Participants were asked about their attitudes related to evaluation of
      a) group beneficial research in principle, b) pharmaceutical withdrawal studies
      and c) research authorization. Sociodemographic and clinical variables were
      collected. RESULTS AND DISCUSSION: This study included 85 persons and all of them
      gave their informed consent to participation. The mean age was 70 years, 47% were
      male, 61% had a university degree and 46% an independent profession. Mild
      cognitive impairment was diagnosed in 26%. This survey revealed a relatively high
      basic approval of group beneficial dementia research as well as of pharmaceutical
      withdrawal studies. In addition, research authorization gained a substantially
      positive evaluation. Only a few participants were informed about the new law in
      force since 2017. The present results were drawn from an explorative study with
      an unrepresentative sample and, therefore, have to be interpreted with caution.
      They show, however, that in the general population more information and awareness
      about group beneficial research with persons incapable of giving informed consent
      should be achieved. The relatively high rate of approval in this study may reveal
      a widespread feeling of social responsibility; however, reported objections of
      the participants should also be seriously considered.

PMID- 29663020
TI  - The self-association and thermal denaturation of caprine and bovine beta
      lactoglobulin.
AB  - Milk components, such as proteins and lipids, have different physicochemical
      properties depending upon the mammalian species from which they come.
      Understanding the different responses of these milks to digestion, processing,
      and differences in their immunogenicity requires detailed knowledge of these
      physicochemical properties. Here we report on the oligomeric state of beta
      lactoglobulin from caprine milk, the most abundant protein present in the whey
      fraction. At pH 2.5 caprine beta-lactoglobulin is predominantly monomeric,
      whereas bovine beta-lactoglobulin exists in a monomer-dimer equilibrium at the
      same protein concentrations. This behaviour was also observed in molecular
      dynamics simulations and can be rationalised in terms of the amino acid
      substitutions present between caprine and bovine beta-lactoglobulin that result
      in a greater positive charge on each subunit of caprine beta-lactoglobulin at low
      pH. The denaturation of beta-lactoglobulin when milk is heat-treated contributes
      to the fouling of heat-exchange surfaces, reducing yields and increasing cleaning
      costs. The bovine and caprine orthologues of beta-lactoglobulin display different
      responses to thermal treatment, with caprine beta-lactoglobulin precipitating at
      higher pH values than bovine beta-lactoglobulin (pH 7.1 compared to pH 5.6) that
      are closer to the natural pH of these milks (pH 6.7). This property of caprine
      beta-lactoglobulin likely contributes to the reduced heat stability of caprine
      milk compared to bovine milk at its natural pH.

PMID- 29663022
TI  - [Diagnostics and conservative treatment of cervical and lumbar spinal stenosis].
AB  - BACKGROUND: Degenerative stenotic spondylosis is not an uncommon cause of
      cervical spondylotic myelopathy (CSM) and cauda equina lesions in the aged
      population. Limited standardization exists with respect to diagnostic and
      therapeutic procedures. OBJECTIVE: Literature review with respect to diagnostic
      and therapeutic procedures for neurologically relevant cervical and lumbar
      spinals stenosis. MATERIAL AND METHODS: Comprehensive literature review. RESULTS
      AND CONCLUSION: Clinical neurological examination and diagnostic imaging are
      fundamental for the diagnosis of neurologically relevant cervical and lumbar
      spinal stenosis. Additional laboratory blood and cerebrospinal fluid testing
      might be required for a differential diagnosis. Neurophysiological testing is
      reserved for specific clinical problems. The clinical evidence for the efficacy
      of conservative therapeutic strategies is limited.

PMID- 29663023
TI  - Grasping trajectories in a virtual environment adhere to Weber's law.
AB  - Virtual-reality and telerobotic devices simulate local motor control of virtual
      objects within computerized environments. Here, we explored grasping kinematics
      within a virtual environment and tested whether, as in normal 3D grasping,
      trajectories in the virtual environment are performed analytically, violating
      Weber's law with respect to object's size. Participants were asked to grasp a
      series of 2D objects using a haptic system, which projected their movements to a
      virtual space presented on a computer screen. The apparatus also provided object
      specific haptic information upon "touching" the edges of the virtual targets. The
      results showed that grasping movements performed within the virtual environment
      did not produce the typical analytical trajectory pattern obtained during 3D
      grasping. Unlike as in 3D grasping, grasping trajectories in the virtual
      environment adhered to Weber's law, which indicates relative resolution in size
      processing. In addition, the trajectory patterns differed from typical
      trajectories obtained during 3D grasping, with longer times to complete the
      movement, and with maximum grip apertures appearing relatively early in the
      movement. The results suggest that grasping movements within a virtual
      environment could differ from those performed in real space, and are subjected to
      irrelevant effects of perceptual information. Such atypical pattern of visuomotor
      control may be mediated by the lack of complete transparency between the
      interface and the virtual environment in terms of the provided visual and haptic
      feedback. Possible implications of the findings to movement control within
      robotic and virtual environments are further discussed.

PMID- 29663024
TI  - Neural motor control differs between bimanual common-goal vs. bimanual dual-goal
      tasks.
AB  - Coordinating bimanual movements is essential for everyday activities. Two common
      types of bimanual tasks are common goal, where two arms share a united goal, and
      dual goal, which involves independent goals for each arm. Here, we examine how
      the neural control mechanisms differ between these two types of bimanual tasks.
      Ten non-disabled individuals performed isometric force tasks of the elbow at 10%
      of their maximal voluntary force in both bimanual common and dual goals as well
      as unimanual conditions. Using transcranial magnetic stimulation, we concurrently
      examined the intracortical inhibitory modulation (short-interval intracortical
      inhibition, SICI) as well as the interlimb coordination strategies utilized
      between common- vs. dual-goal tasks. Results showed a reduction of SICI in both
      hemispheres during dual-goal compared to common-goal tasks (dominant hemisphere:
      P = 0.04, non-dominant hemisphere: P = 0.03) and unimanual tasks (dominant
      hemisphere: P = 0.001, non-dominant hemisphere: P = 0.001). For the common-goal
      task, a reduction of SICI was only seen in the dominant hemisphere compared to
      unimanual tasks (P = 0.03). Behaviorally, two interlimb coordination patterns
      were identified. For the common-goal task, both arms were organized into a
      cooperative "give and take" movement pattern. Control of the non-dominant arm
      affected stabilization of bimanual force (R2 = 0.74, P = 0.001). In contrast, for
      the dual-goal task, both arms were coupled together in a positive fashion and
      neither arm affected stabilization of bimanual force (R2 = 0.31, P = 0.1). The
      finding that intracortical inhibition and interlimb coordination patterns were
      different based on the goal conceptualization of bimanual tasks has implications
      for future research.

PMID- 29663025
TI  - Imaging appearance of well-differentiated liposarcomas with myxoid stroma.
AB  - OBJECTIVE: Describe the imaging appearance of well-differentiated liposarcoma
      with myxoid stroma (WDLMS) and correlate with histopathology. MATERIALS AND
      METHODS: A keyword search of the institution medical records was performed from 1
      January 2000 to 30 June 2017. The histopathology slides of cases identified in
      this fashion were then reviewed by a pathologist. Additional cases were
      prospectively collected from extramural referrals and tumor boards. Diagnostic
      imaging studies of pathologically proven cases of WDLMS were then reviewed in
      consensus and correlated with pathology. RESULTS: Ten cases of pathologically
      proven WDLMS were identified (7 men, 3 women, ages 26-81). Tumor location
      included the retroperitoneum (n = 5), thigh (n = 4), and the shin (n = 1). Nine
      patients had macroscopic fat on imaging. The nonlipomatous components had a
      variable appearance, including septal, nodular, and lacelike patterns. Two cases
      included two distinct areas that were predominantly myxoid or lipomatous ("bi
      morphic"). One tumor had no macroscopic fat on imaging. On CT, the nonlipomatous
      nodular components were hypodense/had hypodense areas. On MRI, the nodular
      components had intermediate/bright T2W signal. Interval nonlipomatous nodular
      growth was identified in 3 cases. CONCLUSION: WDLMS may present on imaging as a
      mass with variable morphology and amounts of nonlipomatous components.
      Histopathological diagnosis of WDLMS is challenging and imaging correlation may
      be helpful, as this tumor may have >=50% fatty volume, may have a myxoid nodular
      component or bi-morphic appearance, or may be located in the retroperitoneum,
      features that are unusual for myxoid liposarcoma. WDLMS with a nodular component
      cannot be distinguished from dedifferentiated liposarcoma based on imaging alone.

PMID- 29663026
TI  - CT-guided biopsy in suspected spondylodiscitis: microbiological yield, impact on
      antimicrobial treatment, and relationship with outcome.
AB  - PURPOSE: To investigate the clinical impact of CT-guided biopsy, as performed in
      routine clinical practice, in patients with suspected spondylodiscitis on MRI in
      terms of culture yield, impact on antimicrobial treatment, and outcome. METHODS:
      This study included 64 patients with MRI findings compatible with
      spondylodiscitis who underwent CT-guided biopsy. RESULTS: Initial CT-guided
      biopsies were culture-positive in 20/64 (31.3%, 95% confidence interval [CI] 21.2
      43.3%). Repeat CT-guided biopsies (after initial negative biopsy) were culture
      positive in an additional 5/15 (33.3%, 95% CI 15.2-58.3%). Serum leukocytes, C
      reactive protein, pre-biopsy use of antibiotics, neurological symptoms, MRI
      findings, vertebral height loss, and hyperkyphosis were not significantly
      different between culture-positive and culture-negative cases (P = 0.214-1.000);
      75% (15/20) of initial CT-guided biopsies that were culture-positive provided
      additional information to clinicians for guiding antibiotic treatment. Sixty-two
      of 64 patients (96.9%, 95% CI 89.3-99.1%) would have been adequately treated if a
      strategy was followed that would subject all patients without clinical findings
      suspicious for "atypical" microorganisms and negative blood cultures to empirical
      antibiotics (i.e., clindamycin for coverage of Gram-positive bacteria) without
      using biopsy results to determine the optimal antibiotic regimen. Outcome within
      6 months (development of neurologic or orthopedic complications, surgery, and
      death) was not significantly different (P = 0.751) between culture-positive and
      culture-negative patients. CONCLUSIONS: Although CT-guided biopsies are culture
      positive in a minority of cases, the majority of positive cultures are useful to
      tailor antibiotic treatment. Empirical treatment with clindamycin may cover
      almost all micro-organisms in positive biopsy specimens, provided patients are
      not immunocompromised. Outcome appears similar between culture-positive and
      culture-negative patients.

PMID- 29663028
TI  - Successful full-dose DeVIC therapy in a patient with advanced-stage extranodal
      natural killer/T-cell lymphoma refractory to L-asparaginase.

PMID- 29663027
TI  - Molecular interactions at the surface of extracellular vesicles.
AB  - Extracellular vesicles such as exosomes, microvesicles, apoptotic bodies, and
      large oncosomes have been shown to participate in a wide variety of biological
      processes and are currently under intense investigation in many different fields
      of biomedicine. One of the key features of extracellular vesicles is that they
      have relatively large surface compared to their volume. Some extracellular
      vesicle surface molecules are shared with those of the plasma membrane of the
      releasing cell, while other molecules are characteristic for extracellular
      vesicular surfaces. Besides proteins, lipids, glycans, and nucleic acids are also
      players of extracellular vesicle surface interactions. Being secreted and present
      in high number in biological samples, collectively extracellular vesicles
      represent a uniquely large interactive surface area which can establish contacts
      both with cells and with molecules in the extracellular microenvironment. Here,
      we provide a brief overview of known components of the extracellular vesicle
      surface interactome and highlight some already established roles of the
      extracellular vesicle surface interactions in different biological processes in
      health and disease.

PMID- 29663029
TI  - Yttrium-90 ibritumomab tiuxetan (Zevalin) followed by BEAM (Z-BEAM) conditioning
      regimen and autologous stem cell transplantation (ASCT) in relapsed or refractory
      high-risk B-cell non-Hodgkin lymphoma (NHL): a single institution Italian
      experience.
AB  - Chemo-refractory NHL has a very poor outcome; the addiction of RIT to salvage
      regiment pre ASCT had recently demonstrated promising results.We performed a
      retrospective sequential study to determine the feasibility of standard Zevalin
      with BEAM in high-risk relapse/refractory NHL. A matched cohort analysis with a
      group treated with standard BEAM without Zevalin was performed as secondary
      endpoint. Between October 2006 and January 2013, 37 NHL patients at high risk for
      progression or early (< 1 year) or multiple relapses were treated with Z-BEAM and
      ASCT after R-DHAP or R-ICE as salvage therapy. Clinical characteristics were 19
      refractory and 18 early or multiple relapse; 16 patients received 1, and 21 had 2
      or more previous rituximab-containing chemotherapy. At the end of treatment,
      response was CR 22 (59%), PR 10 (27%), PD 4 (11%), and toxic death (TD) 1 (3%).
      With a median follow up of 61 months, 3-year PFS was 61% and OS 61%. Fifteen
      patients died, 12 of lymphoma. Comparison with 21 treated with BEAM alone showed
      a numerical higher 3-yr PFS rate in favor of Z-BEAM but not statistically
      significant (57 vs 48%). With the limitation of the small sample subgroup
      analysis, a significant benefit was observed in relapsed patients for PFS (78% Z
      BEAM vs 22% BEAM p = 0.016) and OS (83% Z-BEAM vs 22% BEAM p = 0.001). In
      relapsed/refractory high-risk NHL, Z-BEAM+ASCT is able to achieve a good ORR.
      Three-year PFS is promising for early relapsed patients but is not satisfactory
      for those with refractory disease.